PMID- 19087993
TI  - The perfect is the enemy of the good (excerpt: full version at www.ccjm.org).

PMID- 19087994
TI  - Let's not retreat (excerpt: full version at www.ccjm.org).

PMID- 19087995
TI  - We're chart doctors now.

PMID- 19087996
TI  - Nails in the coffin.

PMID- 19087997
TI  - I was never a hospital guy (excerpt: full version at www.ccjm.org).

PMID- 19087998
TI  - We must work together to save health care in our country.

PMID- 19087999
TI  - Focus on improving care (excerpt: full version at www.ccjm.org).

PMID- 19088001
TI  - General internal medicine is extinct.

PMID- 19088002
TI  - Black hairy tongue.

PMID- 19088003
TI  - Carcinoid tumors: what should increase our suspicion?
AB  - Carcinoid tumors are neuroendocrine neoplasms, primarily of the gastrointestinal
      tract. Their incidence has been increasing over the last 2 to 3 decades. Patients
      often present with vague, nonspecific symptoms. Thus, primary care physicians
      should keep this diagnosis in mind and start appropriate diagnostic testing if
      they suspect it on a clinical basis. Patients with carcinoid tumors are also at
      increased risk of developing other malignancies, so close follow-up by their
      primary care physician is necessary.

PMID- 19088004
TI  - Parkinson disease: not just a movement disorder.
AB  - Nonmotor symptoms are common in Parkinson disease and can significantly worsen
      the health and quality of life of the patient and family members. These symptoms
      can be broadly categorized as sensory, autonomic, cognitive-behavioral, and sleep
      related. Clinicians can improve the care of these patients by recognizing and
      addressing these problems.

PMID- 19088005
TI  - 2008-2009 Influenza update: a better vaccine match.
AB  - Last year, the influenza vaccine did not match the circulating strains very well,
      and its overall protective efficacy was only 40%. All three antigens contained in
      the 2008-2009 vaccine are new. Surveillance data from the Southern Hemisphere
      during the summer of 2008 show that this vaccine is expected to match well the
      circulating strains in the Northern Hemisphere.

PMID- 19088006
TI  - Bisphosphonates and osteonecrosis of the jaw: innocent association or significant
      risk?
AB  - Published case series and systematic reviews have documented an association
      between bisphosphonates and osteonecrosis of the jaw. However, a cause-and-effect
      relationship has not been established, and most of the reported cases have been
      in patients with cancer who were receiving much higher doses than those used to
      treat osteoporosis or Paget disease of bone. The risk, if any, to patients with
      these latter conditions receiving these drugs appears to be very small.

PMID- 19088007
TI  - Hepatitis B virus infection: understanding its epidemiology, course, and
      diagnosis.
AB  - Although hepatitis B virus (HBV) infection is not as common in the United States
      as in some countries, 5000 Americans die from it every year. This number can be
      significantly decreased with proper screening and by vaccinating people at risk.
      Internists should be aware of the natural history of HBV infection, a vital
      prerequisite to correctly assessing disease severity and subsequently determining
      the need for antiviral therapy.

PMID- 19088009
TI  - The genetic basis for type 1 diabetes.
AB  - BACKGROUND: Type 1 diabetes (T1D) is characterized by autoimmune destruction of
      insulin-producing beta-cells in the pancreas resulting from the action of
      environmental factors on genetically predisposed individuals. The increasing
      incidence over recent decades remains unexplained, but the capacity of
      identifying infants at highest genetic risk has become an increasing requirement
      for potential therapeutic intervention trials. SOURCES OF DATA: Literature
      searches on T1D and genes were carried out, and key papers since the 1970s were
      highlighted for inclusion in this review. AREAS OF AGREEMENT: Early genetic
      studies identified the most important region for genetic susceptibility to T1D
      the human leukocyte antigen genes on chromosome 6; later shown to contribute
      approximately half of the genetic determination of T1D. The other half is made up
      of multiple genes, each having a limited individual impact on genetic
      susceptibility. AREAS OF CONTROVERSY: Historically, there have been many
      controversial genetic associations with T1D, mostly caused by underpowered case
      control studies but these are now decreasing in frequency. AREAS OF GROWTH: The
      functional effect of each gene associated with T1D must be investigated to
      determine its usefulness both in risk assessment and as a potential therapeutic
      target. AREAS TIMELY FOR DEVELOPING RESEARCH: Recently identified copy number
      variants in DNA and epigenetic modifications (heritable changes not associated
      with changes in the DNA sequence) are also likely to play a role in genetic
      susceptibility to T1D.

PMID- 19088010
TI  - Does loss of CD151 expression promote the metastasis of hypoxic colon cancer
      cells?
AB  - Intratumoral hypoxia increases invasion and metastasis through multiple
      mechanisms, including changes in gene expression that are mediated by hypoxia
      inducible factor 1. In hypoxic colon cancer cells, hypoxia-inducible factor 1
      inhibits the expression of CD151, a cell surface molecule that normally tethers
      epithelial cells to the basement membrane, which may promote metastasis.

PMID- 19088011
TI  - Toward a cure for chronic myeloid leukemia.

PMID- 19088012
TI  - Translating an Antagonist of Chemokine Receptor CXCR4: from bench to bedside.
AB  - The majority of current cancer therapies focus on a primary tumor approach.
      However, it is metastases that cause the majority of cancer deaths. The
      metastatic process has been shown repeatedly to be greatly influenced by
      chemokines such as CXCL12 [stromal cell derived factor-1 (SDF-1)] and its
      receptor CXCR4. The activation of this pathway has been reported to modulate cell
      migration, survival, proliferation, and gene transcription through G proteins,
      phosphoinositide-3 kinase, Akt, extracellular signal-regulated kinase, arrestin,
      and Janus-activated kinase/signal transducers and activators of transcription. A
      wide variety of strategies, such as peptides, small molecules, antibodies, and
      small interfering RNA, have been used to target this pathway. Treatments in
      combination with current therapies seem to be especially promising in preclinical
      studies. A few compounds are advancing into early stages of clinical development.
      In this article, we will review the development of CXCR4 antagonists in oncology.

PMID- 19088013
TI  - High shed antigen levels within tumors: an additional barrier to immunoconjugate
      therapy.
AB  - Shedding of cell surface antigens is an important biological process that is used
      by cells to modulate responses to signals in the extracellular environment.
      Because antibody-based therapies of cancer target cell surface antigens, it is
      important to understand more about the shedding process and how it affects tumor
      responses to this type of therapy. Up to now most attention has been focused on
      measuring the concentration of shed antigens in the blood and using these to
      determine the presence of a tumor and as a measure of response. The recent
      finding that the concentration of the tumor antigen mesothelin is extremely high
      within the interstitial space of tumors, where it can block antibody action, and
      that the concentration of shed mesothelin within the tumor is lowered by
      chemotherapy has important implications for the successful treatment of solid
      tumors by immunoconjugates and whole antibodies.

PMID- 19088014
TI  - CCR focus: breast cancer.

PMID- 19088015
TI  - Advances in breast cancer: pathways to personalized medicine.
AB  - Breast cancer is a complex disease caused by the progressive accumulation of
      multiple gene mutations combined with epigenetic dysregulation of critical genes
      and protein pathways. There is substantial interindividual variability in both
      the age at diagnosis and phenotypic expression of the disease. With an estimated
      1,152,161 new breast cancer cases diagnosed worldwide per year, cancer control
      efforts in the postgenome era should be focused at both population and individual
      levels to develop novel risk assessment and treatment strategies that will
      further reduce the morbidity and mortality associated with the disease. The
      discovery that mutations in the BRCA1 and BRCA2 genes increase the risk of breast
      and ovarian cancers has radically transformed our understanding of the genetic
      basis of breast cancer, leading to improved management of high-risk women. A
      better understanding of tumor host biology has led to improvements in the
      multidisciplinary management of breast cancer, and traditional pathologic
      evaluation is being complemented by more sophisticated genomic approaches. A
      number of genomic biomarkers have been developed for clinical use, and
      increasingly, pharmacogenetic end points are being incorporated into clinical
      trial design. For women diagnosed with breast cancer, prognostic or predictive
      information is most useful when coupled with targeted therapeutic approaches,
      very few of which exist for women with triple-negative breast cancer or those
      with tumors resistant to chemotherapy. The immediate challenge is to learn how to
      use the molecular characteristics of an individual and their tumor to improve
      detection and treatment, and ultimately to prevent the development of breast
      cancer. The five articles in this edition of CCR Focus highlight recent advances
      and future directions on the pathway to individualized approaches for the early
      detection, treatment, and prevention of breast cancer.

PMID- 19088016
TI  - Genetic susceptibility loci for breast cancer by estrogen receptor status.
AB  - Breast cancer is a heterogeneous disease, and risk factors could be
      differentially associated with the development of distinct tumor subtypes that
      manifest different biological behavior and progression. In support of this view,
      there is growing evidence that known breast cancer risk factors vary by hormone
      receptor status and perhaps other pathologic characteristics of disease. Recent
      work from large consortial studies has led to the discovery of novel breast
      cancer susceptibility loci in genic (CASP8, FGFR2, TNRC9, MAP3K1, LSP1) and
      nongenic regions (8q24, 2q35, 5p12) of the genome, and to the finding of
      substantial heterogeneity by tumor characteristics. In particular, susceptibility
      loci in FGFR2, TNRC9, 8q24, 2q35, and 5p12 have stronger associations for
      estrogen receptor-positive (ER+) disease than estrogen receptor-negative (ER -)
      disease. These findings suggest that common genetic variants can influence the
      pathologic subtype of breast cancer, and provide further support for the
      hypothesis that ER+ and ER(-) disease result from different etiologic pathways.
      Current studies had limited power to detect susceptibility loci for less common
      tumor subtypes, such as ER(-) disease including triple-negative and basal-like
      tumors. Ongoing work targeting uncommon subtypes is likely to identify additional
      tumor-specific susceptibility loci in the near future. Characterization of
      etiologic heterogeneity of breast cancer may lead to improvements in the
      understanding of the biological mechanisms for breast cancer, and ultimately
      result in improvements in prevention, early detection, and treatment.

PMID- 19088017
TI  - Triple-negative breast cancer: risk factors to potential targets.
AB  - Triple-negative breast cancer has recently been recognized as an important
      subgroup of breast cancer with a distinct outcome and therapeutic approach when
      compared with other subgroups of breast cancer. Triple-negative breast cancer
      comprises primarily, but not exclusively, a molecularly distinct subtype of
      breast cancer, the basal-like subtype. We do not yet have an assay to identify
      basal-like breast cancer in clinical samples, so triple-negative breast cancer
      has become a commonly used proxy for this subtype. The molecular biology and
      pathophysiology of triple-negative breast cancer are not completely understood,
      but understanding is improving rapidly with the advent of sophisticated molecular
      biology platforms. Moreover, the established risk factors of breast cancer as a
      whole may not apply to this unique subgroup of patients. Finally, because triple
      negative breast cancer is defined by the absence of a target, there are currently
      limitations to using a tailored therapeutic approach, leaving conventional
      cytotoxic therapies as the mainstay. Active preclinical and clinical research
      programs focus on defining the clinical behavior, delineating the risk factors,
      and more completely understanding the molecular biology of triple-negative breast
      cancer to improve prevention, optimize conventional agents, and unveil novel
      therapeutic targets. This CCR focus article will review the current state of the
      art on triple-negative breast cancer.

PMID- 19088018
TI  - Emerging biomarkers and new understanding of traditional markers in personalized
      therapy for breast cancer.
AB  - The era of personalized medicine is likely to see an escalation in the use of
      biomarkers to ensure breast cancer patients receive optimal treatment. A
      combination of prognostic and predictive biomarkers should enable better
      quantification of the residual risk faced by patients and indicate the potential
      value of additional treatment. Established biomarkers such as estrogen receptor
      and progesterone receptor already play a significant role in the selection of
      patients for endocrine therapy. Human epidermal growth factor receptor 2 (HER2)
      is recognized as a strong predictor of response to trastuzumab whereas, more
      recently, the role of estrogen receptor and HER2 as negative and positive
      indicators for chemotherapy has also been explored. Ki67 has traditionally been
      recognized as a modest prognostic factor, but recent neoadjuvant studies suggest
      that on-treatment measurement may be a more effective predictor of treatment
      efficacy for both endocrine treatment and chemotherapy. The last decade has seen
      the emergence of numerous multigene expression profiles that aim to outdo
      traditional predictive and prognostic factors. The Oncotype DX assay and the
      MammaPrint profile are currently undergoing prospective clinical trials to
      clearly define their role. Other gene expression-based assays also show potential
      but are yet to be tested clinically. Rigorous comparison of these emerging
      markers with current treatment selection criteria will be required to determine
      whether they offer significant benefit to justify their use.

PMID- 19088019
TI  - Pharmacogenetics in breast cancer therapy.
AB  - Interindividual and interethnic variability of drug pharmacokinetics and
      pharmacodynamics may be contributed by commonly occurring genetic polymorphisms
      of drug-metabolizing enzymes and transporters. Polymorphisms of CYP2D6 in
      particular have been associated with effects on tamoxifen disposition and
      clinical efficacy, with interethnic differences in distribution of functional
      alleles that affect metabolizer phenotype. Other tamoxifen-related genetic
      variants of CYP3A4, CYP3A5, and sulfotransferase1A1 (SULT1A1) are also briefly
      reviewed here. Polymorphisms of CYP19A1 (aromatase gene) have been reported to
      correlate with clinical outcomes from aromatase inhibitors in small studies but
      require further confirmation. Many studies on chemotherapy are based on
      hypothesis-generating association studies and need to be validated through larger
      scale cooperative group studies. For anthracyclines, polymorphisms in genes such
      as carbonyl reductase 3 (CBR3), ATP-binding cassette subfamily B, member 1
      (ABCB1), glutathione-related transporter genes, and oxidative stress-related
      genes have been reported to correlate with clinical outcomes. The
      pharmacogenetics of taxanes has been extensively investigated, but associations
      of genetic polymorphisms in drug-metabolizing enzymes and transporters reported
      in earlier small studies have not been validated in a recent large clinical
      trial. Allelic variants associated with gemcitabine, capecitabine/5-fluorouracil,
      vinorelbine, and platinum disposition are reviewed. No pharmacogenetic studies
      have been published for targeted agents thus far, although several potential
      candidate genes warrant investigation. Future pharmacogenetic studies will need
      to focus on integration of multiple drug pathways to allow a more comprehensive
      analysis of genetic factors influencing drug efficacy and toxicity.

PMID- 19088020
TI  - Neuropilin-2-mediated tumor growth and angiogenesis in pancreatic adenocarcinoma.
AB  - PURPOSE: Neuropilin-2 (NRP-2) is a coreceptor for vascular endothelial growth
      factor (VEGF) on endothelial cells. NRP-2 is overexpressed in pancreatic ductal
      adenocarcinoma (PDAC) cells relative to nonmalignant ductal epithelium. This
      study determined the role of NRP-2 in PDAC cells. EXPERIMENTAL DESIGN: NRP-2
      expression was reduced in PDAC cells with stable short-hairpin RNA (shRNA)
      transfection. Western blotting was done to evaluate signaling intermediates.
      Migration and invasion studies were carried out in Boyden chambers. Anchorage
      independent growth was assessed by soft-agar colony formation. In vivo growth was
      evaluated using murine subcutaneous and orthotopic xenograft models.
      Immunohistochemical analysis evaluated in vivo proliferation and angiogenesis.
      RESULTS: shRNA-NRP-2 decreased NRP-2 levels without affecting neuropilin-1
      levels. Akt activation was decreased in clones with reduced NRP-2 (shRNA-NRP-2).
      shRNA-NRP-2 cells showed decreased migration, invasion, and anchorage-independent
      growth compared with control cells. In vitro proliferation rates were similar in
      control- and shRNA-transfected cells. Subcutaneous and orthotopic xenografts from
      shRNA-transfected cells were significantly smaller than those resulting from
      control-transfected cells (P < 0.05). Furthermore, shRNA-NRP-2 tumors exhibited
      less cellular proliferation and decreased microvascular area relative to control
      tumors (P < 0.05). Constitutive expression of the angiogenic mediator Jagged-1
      was reduced in shRNA-NRP-2 cells, whereas vascular endothelial growth factor
      levels were unchanged. CONCLUSION: Reduction of NRP-2 expression in PDAC cells
      decreased survival signaling, migration, invasion, and ability to grow under
      anchorage-independent conditions. In vivo, reduction of NRP-2 led to decreased
      growth of xenograft tumors and decreased vascular area, which was associated with
      decreased Jagged-1 levels. NRP-2 is a potential therapeutic target on PDAC cells.

PMID- 19088021
TI  - DNA copy-number alterations underlie gene expression differences between
      microsatellite stable and unstable colorectal cancers.
AB  - PURPOSE: About 15% of colorectal cancers harbor microsatellite instability (MSI).
      MSI-associated gene expression changes have been identified in colorectal
      cancers, but little overlap exists between signatures hindering an assessment of
      overall consistency. Little is known about the causes and downstream effects of
      differential gene expression. EXPERIMENTAL DESIGN: DNA microarray data on 89 MSI
      and 140 microsatellite-stable (MSS) colorectal cancers from this study and 58 MSI
      and 77 MSS cases from three published reports were randomly divided into test and
      training sets. MSI-associated gene expression changes were assessed for cross
      study consistency using training samples and validated as MSI classifier using
      test samples. Differences in biological pathways were identified by functional
      category analysis. Causation of differential gene expression was investigated by
      comparison to DNA copy-number data. RESULTS: MSI-associated gene expression
      changes in colorectal cancers were found to be highly consistent across multiple
      studies of primary tumors and cancer cell lines from patients of different
      ethnicities (P < 0.001). Clustering based on consistent changes separated
      additional test cases by MSI status, and classification of individual samples
      predicted MSI status with a sensitivity of 96% and specificity of 85%. Genes
      associated with immune response were up-regulated in MSI cancers, whereas genes
      associated with cell-cell adhesion, ion binding, and regulation of metabolism
      were down-regulated. Differential gene expression was shown to reflect systematic
      differences in DNA copy-number aberrations between MSI and MSS tumors (P <
      0.001). CONCLUSIONS: Our results show cross-study consistency of MSI-associated
      gene expression changes in colorectal cancers. DNA copy-number alterations partly
      cause the differences in gene expression between MSI and MSS cancers.

PMID- 19088022
TI  - Cytosolic phospholipase A2-alpha: a potential therapeutic target for prostate
      cancer.
AB  - PURPOSE: Cytosolic phospholipase A2-alpha (cPLA2-alpha) provides intracellular
      arachidonic acid to supply both cyclooxygenase and lipoxygenase pathways. We aim
      to determine the expression and activation of cPLA2-alpha in prostate cancer cell
      lines and tissue and the effect of targeting cPLA2-alpha in vitro and in vivo.
      EXPERIMENTAL DESIGN: The expression of cPLA2-alpha was determined in prostate
      cancer cells by reverse transcription-PCR, Western blot, and immunocytochemistry.
      Growth inhibition, apoptosis, and cPLA2-alpha activity were determined after
      inhibition with cPLA2-alpha small interfering RNA or inhibitor (Wyeth-1).
      Cytosolic PLA2-alpha inhibitor or vehicle was also administered to prostate
      cancer xenograft mouse models. Finally, the expression of phosphorylated cPLA2
      alpha was determined by immunohistochemistry in human normal, androgen-sensitive
      and androgen-insensitive prostate cancer specimens. RESULTS: cPLA2-alpha is
      present in all prostate cancer cells lines, but increased in androgen-insensitive
      cells. Inhibition with small interfering RNA or Wyeth-1 results in significant
      reductions in prostate cancer cell numbers, as a result of reduced proliferation
      as well as increased apoptosis, and this was also associated with a reduction in
      cPLA2-alpha activity. Expression of cyclin D1 and phosphorylation of Akt were
      also observed to decrease. Wyeth-1 inhibited PC3 xenograft growth by
      approximately 33% and again, also reduced cyclin D1. Immunohistochemistry of
      human prostate tissue revealed that phosphorylated cPLA2-alpha is increased when
      hormone refractory is reached. CONCLUSIONS: Expression and activation of cPLA2
      alpha are increased in the androgen-insensitive cancer cell line and tissue.
      Inhibition of cPLA2-alpha results in cells and xenograft tumor growth inhibition
      and serves as a potentially effective therapy for hormone refractory prostate
      cancer.

PMID- 19088023
TI  - miR-192 Regulates dihydrofolate reductase and cellular proliferation through the
      p53-microRNA circuit.
AB  - PURPOSE: The purpose of this study is to investigate the molecular mechanism of
      miR-192 in colon cancer. EXPERIMENTAL DESIGN: Human colon cancer cell lines with
      different p53 status were used as our model system to study the effect of miR-192
      on cell proliferation, cell cycle control, and mechanism of regulation. RESULTS:
      Our results show that one of the key miR-192 target genes is dihydrofolate
      reductase (DHFR). miR-192 affects cellular proliferation through the p53-miRNA
      circuit. Western immunoblot analyses indicated that the expression of DHFR was
      significantly decreased by miR-192. Further investigation revealed that such
      suppression was due to translational arrest rather than mRNA degradation. More
      profound inhibition of cellular proliferation was observed by ectopic expression
      of miR-192 in colon cancer cell lines containing wild-type p53 than cells
      containing mutant p53. Thus, the effect of miR-192 on cellular proliferation is
      mainly p53 dependent. Overexpression of miR-192 triggered both G1 and G2 arrest
      in HCT-116 (wt-p53) cells but not in HCT-116 (null-p53) cells. The cell cycle
      checkpoint control genes p53 and p21 were highly overexpressed in cells that
      overexpressed miR-192. Endogenous miR-192 expression was increased in HCT-116 (wt
      p53) and RKO (wt-p53) cells treated with methotrexate, which caused an induction
      of p53 expression. Chromatin immunoprecipitation-quantitative reverse
      transcription-PCR analysis revealed that the p53 protein interacted with the miR
      192 promoter sequence. CONCLUSION: These results indicate that miR-192 may be
      another miRNA candidate that is involved in the p53 tumor suppressor network with
      significant effect on cell cycle control and cell proliferation.

PMID- 19088024
TI  - Evidence for polyclonal origin of multifocal clear cell renal cell carcinoma.
AB  - PURPOSE: Renal cell carcinomas are often multifocal. We investigated the genomic
      signatures of multifocal clear cell renal cell carcinoma to determine whether
      multiple tumors in the same kidney bear a clonal relationship to one another.
      EXPERIMENTAL DESIGN: A total of 62 tumors from 26 patients who underwent radical
      nephrectomy were examined. All patients had multiple separate clear cell renal
      carcinomas. Loss of heterozygosity analyses were done using five microsatellite
      polymorphic markers that represent putative tumor suppressor genes on chromosome
      3p14 (D3S1300), 7q31 (D7S522), 8p22 (D8S261), 9p21 (D9S171), and 17p13 (TP53). X
      chromosome inactivation analyses were also done on the renal tumors from the 10
      female patients. Chromosome 3p deletion status was determined by dual color
      interphase fluorescence in situ hybridization analysis in all tumors. RESULTS:
      Nineteen of the 26 (73%) patients with multifocal clear cell renal cell carcinoma
      showed allelic loss in at least 1 of 5 microsatellite loci in separate tumors
      analyzed. A disconcordant pattern of allelic loss between coexisting kidney
      tumors was observed in 7 cases. Six cases showed discordant 3p deletion patterns
      by dual color interphase fluorescence in situ hybridization analysis. Of the
      eight informative female cases studied by X chromosome inactivation, one showed a
      discordant nonrandom pattern of X chromosome inactivation. Overall, evidence of
      independent origin of the multifocal renal tumors was observed in 12 of 26 cases
      (46%). CONCLUSIONS: Our data suggest that in a significant number of cases of
      multifocal clear cell renal cell carcinoma, the spatially separate tumors are of
      different clonal origin and arise independently.

PMID- 19088025
TI  - The novel nuclear factor-kappaB inhibitor LC-1 is equipotent in poor prognostic
      subsets of chronic lymphocytic leukemia and shows strong synergy with
      fludarabine.
AB  - PURPOSE: We have recently shown that the novel nuclear factor-kappaB (NF-kappaB)
      inhibitor LC-1 is effective in primary chronic lymphocytic leukemia (CLL) cells.
      Here we elucidated the mechanism of action of LC-1, evaluated its relative
      cytotoxicity in prognostic subsets, and investigated its potential synergistic
      interaction with fludarabine. EXPERIMENTAL DESIGN: Ninety-six fully characterized
      CLL cases were assessed for in vitro sensitivity to LC-1 and fludarabine. In
      selected cases, caspase activation, inhibition of Rel A DNA binding, and the
      transcription of CFLAR, BIRC5, and BCL2 were measured before and after exposure
      to LC-1. In addition, the efficacy of LC-1 was assessed in the presence of the
      survival factors CD154 and interleukin-4, and the potential synergistic
      interaction between LC-1 and fludarabine was evaluated. RESULTS: Cell death was
      associated with caspase-3 activation mediated via activation of both caspase-8
      and caspase-9. Apoptosis was preceded by a reduction of nuclear Rel A DNA binding
      and inhibition of CFLAR, BIRC5, and BCL2 transcription. Importantly, LC-1
      overcame the cytoprotective effects by interleukin-4 and CD40 ligand and was
      equipotent in CLL cells derived from good and bad prognostic subsets. LC-1
      exhibited strong synergy with fludarabine, and the combination produced a highly
      significant mean dose reduction index for fludarabine of > 1,000. CONCLUSIONS: In
      view of imminent first-in-man study of LC-1 in Cardiff, these data show an
      important mechanistic rationale for the use of LC-1 in this disease. Furthermore,
      it validates the concept of targeting nuclear factor-kappaB in CLL and identifies
      the therapeutic potential of LC-1 in combination with fludarabine even in
      patients with fludarabine resistance.

PMID- 19088026
TI  - Second-generation anti-carcinoembryonic antigen designer T cells resist
      activation-induced cell death, proliferate on tumor contact, secrete cytokines,
      and exhibit superior antitumor activity in vivo: a preclinical evaluation.
AB  - PURPOSE: This report describes the development and preclinical qualification
      tests of second-generation anti-carcinoembryonic (CEA) designer T cells for use
      in human trials. EXPERIMENTAL DESIGN: The progenitor first-generation
      immunoglobulin-T-cell receptor (IgTCR) that transmits Signal 1-only effectively
      mediated chimeric immune receptor (CIR)-directed cytotoxicity, but expressor T
      cells succumbed to activation-induced cell death (AICD). The second-generation
      CIR (termed "Tandem" for two signals) was designed to transmit TCR Signal 1 and
      CD28 Signal 2 to render T cells resistant to AICD and provide prolonged antitumor
      effect in vivo. RESULTS: A CIR was created that combines portions of CD28,
      TCRzeta, and a single chain antibody domain (sFv) specific for CEA into a single
      molecule (IgCD28TCR). As designed, the gene-modified Tandem T cells exhibit the
      new property of being resistant to AICD, showing instead an accelerated
      proliferation on tumor contact. Tandem T cells are more potent than first
      generation in targeting and lysing CEA+ tumor. Tandem T cells secrete high levels
      of interleukin-2 and IFNgamma on tumor contact that first-generation T cells
      lacked, but secretion was exhaustible, suggesting a need for interleukin-2
      supplementation in therapy even for these second-generation agents. Finally,
      second-generation T cells were more effective in suppressing tumor in animal
      models. CONCLUSION: An advanced generation of anti-CEA designer T cells is
      described with features that promise a more potent and enduring antitumor immune
      response in vivo. These preclinical data qualify the human use of this agent that
      is currently undergoing trial in patients with CEA+ cancers.

PMID- 19088027
TI  - Synergistic antitumor activity of ixabepilone (BMS-247550) plus bevacizumab in
      multiple in vivo tumor models.
AB  - PURPOSE: Angiogenesis is a critical step in the establishment, growth, and
      metastasis of solid tumors, and combination of antiangiogenic agents with
      chemotherapy is an attractive therapeutic option. We investigated the potential
      of ixabepilone, the first in a new class of antineoplastic agents known as
      epothilones, to synergize with antiangiogenic agents to inhibit tumor growth.
      EXPERIMENTAL DESIGN: In vitro and in vivo cytotoxicity of ixabepilone as single
      agent and in combination with two targeted antiangiogenic agents, bevacizumab or
      sunitinib, were examined in preclinical tumor models. Direct effects of the
      agents against endothelial cells was also examined and compared with the effects
      of paclitaxel as single agent and in combination with bevacizumab. RESULTS:
      Ixabepilone showed robust synergistic antitumor activity in combination with
      bevacizumab and sunitinib in preclinical in vivo models derived from breast,
      colon, lung, and kidney cancers. The synergistic antitumor effect was greater
      with ixabepilone compared with paclitaxel. Furthermore, ixabepilone was more
      effective than paclitaxel at killing endothelial cells expressing P-glycoprotein
      in vitro and inhibiting endothelial cell proliferation and tumor angiogenesis in
      vivo. CONCLUSIONS: Ixabepilone may enhance the antitumor effects of
      antiangiogenic therapy by direct cytotoxicity and also indirectly via the killing
      of tumor-associated endothelial cells. Given that ixabepilone has reduced
      susceptibility to drug efflux pumps compared with taxanes, these data may explain
      the increased antiangiogenic and antitumor activity of ixabepilone in combination
      with antiangiogenic agents. Phase II studies to assess the efficacy and safety of
      ixabepilone plus bevacizumab in locally recurrent or metastatic breast cancer are
      planned.

PMID- 19088028
TI  - Induction of Noxa sensitizes human colorectal cancer cells expressing Mcl-1 to
      the small-molecule Bcl-2/Bcl-xL inhibitor, ABT-737.
AB  - PURPOSE: The intrinsic drug resistance of colorectal cancers is related in part
      to overexpression of prosurvival Bcl-2 family proteins. We determined the effects
      of ABT-737, a small-molecule inhibitor of Bcl-2/Bcl-xL but not Mcl-1, on
      apoptosis induction alone and in combination with CPT-11 and explored mechanisms
      underlying their cooperativity. EXPERIMENTAL DESIGN: Human colorectal carcinoma
      cell lines (HCT116 wild-type and Bax(-/-), HT-29, and RKO) were incubated with
      ABT-737 alone and combined with CPT-11 or bortezomib, and cell viability, caspase
      cleavage, and Annexin V labeling were measured. In drug-treated cell lines,
      protein-protein interactions were analyzed by immunoprecipitation. Lentiviral
      short hairpin RNA was used to knockdown Noxa expression. RESULTS: ABT-737 induced
      apoptosis in a dose-dependent manner and its coadministration with the
      topoisomerase I inhibitor, CPT-11, resulted in a synergistic cytotoxic effect.
      Apoptosis induction by the drug combination was associated with enhanced caspase
      8, caspase-9, and caspase-3 activation and poly(ADP-ribose) polymerase cleavage
      that were completely abrogated in Bax knockout cells. ABT-737 unsequestered the
      BH3-only protein Bim from its complex with Bcl-xL or Bcl-2 and disrupted the
      interaction of Bcl-xL with Bak. CPT-11 treatment up-regulated Noxa expression, as
      did bortezomib, and enhanced Noxa/Mcl-1 complexes. CPT-11 also disrupted the Mcl
      1/Bak interaction. Knockdown of Noxa using short hairpin RNA lentiviral
      constructs was shown to significantly attenuate the cytotoxic effect of CPT-11 or
      bortezomib combined with ABT-737 and inhibited caspase-3 cleavage. CONCLUSIONS:
      Induction of Noxa by CPT-11 or bortezomib can sensitize colorectal cancer cells
      expressing Mcl-1 to ABT-737. Up-regulation of Noxa may therefore represent an
      important strategy to enhance the therapeutic efficacy of ABT-737 against
      colorectal cancer and other solid tumors.

PMID- 19088029
TI  - Nuclear factor-kappaB p65/relA silencing induces apoptosis and increases
      gemcitabine effectiveness in a subset of pancreatic cancer cells.
AB  - PURPOSE: Nuclear factor kappaB (NFkappaB) activity may increase survival and
      protect cancer cells from chemotherapy. Therefore, NFkappaB activity may be
      prognostic, and inhibition of NFkappaB may be useful for pancreatic cancer
      therapy. To test these hypotheses, we examined NFkappaB activity and the effects
      of inhibiting NFkappaB in several pancreatic cancer cell lines with differing
      sensitivities to gemcitabine. EXPERIMENTAL DESIGN: The gemcitabine sensitivity of
      pancreatic cancer cell lines BxPC-3, L3.6pl, CFPAC-1, MPanc-96, PANC-1, and MIA
      PaCa-2 were determined by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium
      bromide and fluorescence-activated cell sorting assays. NFkappaB levels were
      determined by electrophoretic mobility shift assay and reporter assays. The
      effects of gemcitabine on NFkappaB activity were determined in vitro and in vivo.
      NFkappaB was inhibited by silencing of the p65/relA subunit using small
      interfering RNA in vitro and by neutral liposomal delivery of small interfering
      RNA in vivo, and the effects were evaluated on gemcitabine sensitivity. RESULTS:
      The cell lines L3.6pl, BxPC-3, and CFPAC-1 were sensitive, whereas MPanc-96, PANC
      1, and MIA PaCa-2 were resistant to gemcitabine. No significant correlation was
      observed between basal NFkappaB activity and gemcitabine sensitivity. Gemcitabine
      treatment did not activate NFkappaB either in vitro or in vivo. Silencing of
      p65/relA induced apoptosis and increased gemcitabine killing of all gemcitabine
      sensitive pancreatic cancer cells. No significant effects, however, were observed
      on gemcitabine-resistant pancreatic cancer cell lines either in vitro or in vivo.
      CONCLUSIONS: NFkappaB activity did not correlate with sensitivity to gemcitabine.
      Silencing of p65/relA was effective alone and in combination with gemcitabine in
      gemcitabine-sensitive but not gemcitabine-resistant pancreatic cancer cells.
      Thus, NFkappaB may be a useful therapeutic target for a subset of pancreatic
      cancers.

PMID- 19088030
TI  - Impact of Abcc2 (Mrp2) and Abcc3 (Mrp3) on the in vivo elimination of
      methotrexate and its main toxic metabolite 7-hydroxymethotrexate.
AB  - PURPOSE: ATP-binding cassette sub-family C member 2 [ABCC2; multidrug resistance
      associated protein 2 (MRP2)] and ABCC3 (MRP3) mediate the elimination of toxic
      compounds, such as drugs and carcinogens, and have a large overlap in substrate
      specificity. We investigated the roles of Abcc2 and Abcc3 in the elimination of
      the anticancer drug methotrexate (MTX) and its toxic metabolite 7
      hydroxymethotrexate (7OH-MTX) in vivo. EXPERIMENTAL DESIGN: Abcc2;Abcc3(-/-) mice
      were generated, characterized, and used to investigate possibly overlapping or
      complementary roles of Abcc2 and Abcc3 in the elimination of MTX and 7OH-MTX
      after i.v. administration of 50 mg/kg MTX. RESULTS: Abcc2;Abcc3(-/-) mice were
      viable and fertile. In Abcc2(-/-) mice, the plasma area under the curve (AUCi.v.)
      for MTX was 2.0-fold increased compared with wild type, leading to 1.6-fold
      increased urinary excretion, which was not seen in Abcc2;Abcc3(-/-) mice. Biliary
      excretion of MTX was 3.7-fold reduced in Abcc2(-/-) but unchanged in Abcc2;Abcc3(
      /-) mice. The plasma AUCi.v.s of 7OH-MTX were 6.0-fold and 4.3-fold increased in
      Abcc2(-/-) and Abcc2;Abcc3(-/-) mice, respectively, leading to increased urinary
      excretion. The biliary excretion of 7OH-MTX was 5.8-fold reduced in Abcc2(-/-)
      but unchanged in Abcc2;Abcc3(-/-) mice. 7OH-MTX accumulated substantially in the
      liver of Abcc2(-/-) and especially Abcc2;Abcc3(-/-) mice. CONCLUSIONS: Abcc2 is
      important for (biliary) excretion of MTX and its toxic metabolite 7OH-MTX. When
      Abcc2 is absent, Abcc3 transports MTX and 7OH-MTX back from the liver into the
      circulation, leading to increased plasma levels and urinary excretion. Variation
      in ABCC2 and/or ABCC3 activity may therefore have profound effects on the
      elimination and severity of toxicity of MTX and 7OH-MTX after MTX treatment of
      patients.

PMID- 19088031
TI  - Design of folate-linked liposomal doxorubicin to its antitumor effect in mice.
AB  - PURPOSE: Tumor cell targeting is a promising strategy for enhancing the
      therapeutic potential of chemotherapy agents. Polyethylene glycol (PEG)-coated
      (sterically stabilized) liposomes show enhanced accumulation on the surface of
      tumors, but steric hindrance by PEGylation reduces the association of the
      liposome-bound ligand with its receptor. To increase folate receptor (FR)
      targeting, we optimized the concentration and PEG spacer length of folate-PEG
      lipid in liposomes. EXPERIMENTAL DESIGN: Three types of folate-linked liposomal
      doxorubicin were designed and prepared by optimizing the concentration and PEG
      spacer length of folate-PEG-lipid in PEGylated or non-PEGylated liposomes and by
      masking folate-linked liposomes where the folate ligand is "masked" by adjacent
      PEG spacers. The liposome targeting efficacy was evaluated in vitro and in vivo.
      RESULTS: In human oral carcinoma KB cells, which overexpress FR, modification
      with sufficiently long PEG spacer and a high concentration of folate ligand to
      non-PEGylated liposomes increased the FR-mediated association and cytotoxicity
      more than with PEGylated and masked folate-linked liposomes. On the contrary, in
      mice bearing murine lung carcinoma M109, modification with the folate ligand in
      PEGylated and masked folate-linked liposomes showed significantly higher
      antitumor effect than with non-PEGylated liposomes irrespective of the length of
      time in the circulation after intravenous injection. CONCLUSIONS: The results of
      this study will be beneficial for the design and preparation of ligand-targeting
      carriers for cancer treatment.

PMID- 19088032
TI  - Inhibition of melanoma growth by targeting of antigen to dendritic cells via an
      anti-DEC-205 single-chain fragment variable molecule.
AB  - PURPOSE: Our goal was to target melanoma antigens to the dendritic cell-specific
      receptor DEC-205. DEC-205 is an antigen receptor expressed on dendritic cells and
      has been shown to guide antigens to MHC class I and II compartments for
      processing and presentation to T cells. EXPERIMENTAL DESIGN: The melanoma tumor
      associated antigen (TAA), gp100, was fused to the single-chain fragment variable
      (scFv) specific for DEC-205. The binding capacity of the scFv was tested on lymph
      node-isolated CD11c+ cells. Mixed lymphocyte reactions were carried out to show
      an increased proliferative capacity of gp100 antigen-specific CD4 and CD8 T
      cells. Furthermore the scFv-TAA was used in a therapeutic setting using two
      different melanoma mouse models. RESULTS: C57Bl/6 mice were injected with scFv
      DEC-205-gp100, monoclonal antibody anti-DEC-205, or PBS. Using fluorescence
      activated cell sorting, we showed that lymph node CD11c+ dendritic cells stained
      positive for the binding of the scFv-mDEC-205-gp100 and the anti-DEC-205
      monoclonal antibody, whereas the PBS-injected animals were negative. In mixed
      lymphocyte reactions, bone marrow-derived dendritic cells pulsed with scFv-mDEC
      205-gp100 significantly increased proliferation of gp100-specific CD8+ and CD4+ T
      cells beyond gp100 peptide-pulsed or nonpulsed bone marrow-derived dendritic
      cells. Finally, in B16/F10 and RET models, a concentration-dependent suppression
      of tumor growth using scFv-mDEC-205-gp100 (66% reduction of tumor volume), in
      comparison with gp100 peptide vaccination, was observed. CONCLUSIONS: Our results
      indicate that the scFv-mDEC-205-gp100 targets TAA to dendritic cells in vivo for
      presentation on both MHC class I and II molecules. In vivo, this leads to an
      improved immune response and a decrease in tumor growth rate.

PMID- 19088033
TI  - Reduction of human melanoma tumor growth in severe combined immunodeficient mice
      by passive transfer of antibodies induced by a high molecular weight melanoma
      associated antigen mimotope vaccine.
AB  - PURPOSE: The high molecular weight melanoma-associated antigen (HMW-MAA) is an
      attractive target for immunotherapy of malignant melanoma. We have recently
      generated a vaccine based on the HMW-MAA mimotope 225D9.2+ that was able to
      induce anti-HMW-MAA antibodies with antitumor activity in vitro. Here, we
      investigated the antitumor activity of these antibodies in a human melanoma
      xenotransplant severe combined immunodeficient (SCID) mouse model. EXPERIMENTAL
      DESIGN: Tumors were established by injecting the human melanoma 518A2 cells into
      C.B.17 SCID/SCID mice. In tumor prevention experiments, 200 microg purified total
      IgG antibodies were injected intravenously the same day or on day 5 in
      therapeutic experiments. Antibody administration was repeated every fourth day
      and tumor volumes were measured. Antibody specificity and tumor infiltration by
      macrophages were investigated by immunohistochemistry. RESULTS: Within 35 days
      after cell inoculation, antibody treatment reduced tumor growth up to 40% in the
      therapeutic and up to 62% in the tumor prevention experiments compared with the
      control mice. In tumors of all groups, a similar distribution of the HMW-MAA and
      no differences in infiltration of macrophages were detected by
      immunohistochemistry. CONCLUSIONS: Here, we showed that antibodies induced by the
      225D9.2+ mimotope effectively inhibited melanoma tumor growth. Additional
      mechanisms besides antibody-dependent cell cytotoxicity like disruption of
      interactions of melanoma cells mediated by extracellular matrix components seem
      to be involved in tumor growth inhibition. Based on our findings, we suggest that
      active immunization with this mimotope might be a promising strategy for
      treatment of melanoma.

PMID- 19088034
TI  - Early tumor drug pharmacokinetics is influenced by tumor perfusion but not plasma
      drug exposure.
AB  - PURPOSE: Pharmacokinetic parameters derived from plasma sampling are used as a
      surrogate of tumor pharmacokinetics. However, pharmacokinetics-modulating
      strategies do not always result in increased therapeutic efficacy. Nonsurrogacy
      of plasma kinetics may be due to tissue-specific factors such as tumor perfusion.
      EXPERIMENTAL DESIGN: To assess the impact of tumor perfusion and plasma drug
      exposure on tumor pharmacokinetics, positron emission tomography studies were
      done with oxygen-15 radiolabeled water in 12 patients, with 6 patients undergoing
      positron emission tomography studies with carbon-11 radiolabeled N-[2
      (dimethylamino)ethyl]acridine-4-carboxamide and the other 6 with fluorine-18
      radiolabeled 5-fluorouracil. RESULTS: We found that tumor blood flow (mL blood/mL
      tissue/minute) was significantly correlated to early tumor radiotracer uptake
      between 4 and 6 minutes [standard uptake value (SUV)4-6; rho = 0.79; P = 0.002],
      tumor radiotracer exposure over 10 minutes [area under the time-activity curve
      (AUC)0-10; predominantly parent drug; rho = 0.86; P < 0.001], and tumor
      radiotracer exposure over 60 minutes (AUC0-60; predominantly radiolabeled
      metabolites; rho = 0.80; P = 0.002). Similarly, fractional volume of distribution
      of radiolabeled water in tumor (Vd) was significantly correlated with SUV4-6 (rho
      = 0.80; P = 0.002), AUC0-10 (rho = 0.85; P < 0.001), and AUC0-60 (rho = 0.66; P =
      0.02). In contrast, no correlation was observed between plasma drug or total
      radiotracer exposure over 60 minutes and tumor drug uptake or exposure. Tumor
      blood flow was significantly correlated to Vd (rho = 0.69; P = 0.014), underlying
      the interdependence of tumor perfusion and Vd. CONCLUSIONS: Tumor perfusion is a
      key factor that influences tumor drug uptake/exposure. Tumor vasculature
      targeting strategies may thus result in improved tumor drug exposure and
      therefore drug efficacy.

PMID- 19088035
TI  - A synovial sarcoma-specific preoperative nomogram supports a survival benefit to
      ifosfamide-based chemotherapy and improves risk stratification for patients.
AB  - PURPOSE: To identify prognostic factors related to outcome in 255 patients with
      synovial sarcoma and to construct a preoperative nomogram to predict the risk of
      disease-specific death. DESIGN: Between July 1982 and June 2006, 301 patients
      underwent treatment at our institution for primary synovial sarcoma of all
      anatomic sites and 255 patients with localized disease at presentation were
      resected with curative intent. Data were collected prospectively and analyzed
      retrospectively. RESULTS: Five-, 10-, and 15-year disease-specific survival (DSS)
      was 72%, 60%, and 53%, respectively. Multivariate analysis revealed size and
      primary tumor site as the only independent adverse predictors of disease-specific
      death. A nomogram based on preoperative data for surgical patients not receiving
      anthracycline-ifosfamide (AI) chemotherapy (n = 196) estimates 3- and 5-year DSS
      with a concordance index of 77.3%. For the first 3 years following diagnosis, the
      observed DSS for patients treated with AI chemotherapy (n = 59) was greater than
      that predicted by the preoperative nomogram based on patients not receiving AI
      chemotherapy. SYT-SSX fusion transcript data were available for 132 patients.
      Multivariate analysis of this subset showed that SYT-SSX1 fusion type was
      predictive of early, but not late, distant recurrence. CONCLUSION: Size and
      location govern prognosis in primary synovial sarcoma resected with curative
      intent. A nomogram based on preoperative variables provides individualized
      patient survival estimates and shows an early survival benefit to chemotherapy
      that may dissipate over time. This nomogram may improve decision-making with
      regards to selecting patients most likely to benefit from neoadjuvant/adjuvant
      chemotherapy.

PMID- 19088036
TI  - Allelic imbalance analysis using a single-nucleotide polymorphism microarray for
      the detection of bladder cancer recurrence.
AB  - PURPOSE: Non-muscle-invasive bladder cancer is a frequently occurring cancer,
      with an extremely high recurrence risk. Recurrence detection is based on cytology
      and urethrocystoscopy. A previous study suggested that a single-nucleotide
      polymorphism (SNP) array may be effective for noninvasive detection of allelic
      imbalances in urine. We investigated whether this method is suitable to detect
      allelic imbalance as an indicator of recurrences in non-muscle-invasive bladder
      cancer follow-up. EXPERIMENTAL DESIGN: DNA from blood and urine from 158 patients
      (113 with and 45 without recurrence) was hybridized to the Affymetrix GeneChip
      Mapping 10K 2.0. Allelic imbalance detection was based on SNPs showing changes
      from heterozygosity in blood to homozygosity in urine and on automatic analysis
      of copy number changes using Copy Number Analyser for GeneChip. RESULTS: Urine
      samples with tumor showed allelic imbalance at 0.4% of all informative SNPs. In
      samples without tumors, 0.04% of these SNPs were affected (P = 0.07). In
      addition, Copy Number Analyser for GeneChip analysis showed more copy number
      changes in samples with a tumor (P = 0.001). Losses and gains of chromosomal
      regions showed clustering, overlapping with known bladder cancer loci. However,
      25 (22%) patients with a tumor recurrence did not display any regions with copy
      number changes, whereas 24 (53%) individuals without a recurrence did. Receiver
      operating characteristic curve analysis using the number of SNPs displaying copy
      number changes from the Copy Number Analyser for GeneChip analysis resulted in an
      area under the curve of only 0.67 (95% confidence interval, 0.58-0.76).
      CONCLUSION: Single-nucleotide polymorphism microarray analysis of allelic
      imbalance in urine cannot replace urethrocystoscopy and cytology for the
      detection of recurrences in non-muscle-invasive bladder cancer follow-up.

PMID- 19088037
TI  - Cancer stem cell analysis and clinical outcome in patients with glioblastoma
      multiforme.
AB  - PURPOSE: Cancer stem cells (CSC) are thought to represent the population of
      tumorigenic cells responsible for tumor development. The stem cell antigen CD133
      identifies such a tumorigenic population in a subset of glioblastoma patients. We
      conducted a prospective study to explore the prognostic potential of CSC analysis
      in glioblastoma patients. EXPERIMENTAL DESIGN: We investigated the relationship
      between the in vitro growth potential of glioblastoma CSCs and patient death or
      disease progression in tumors of 44 consecutive glioblastoma patients treated
      with complete or partial tumorectomy followed by radiotherapy combined with
      temozolomide treatment. Moreover, we evaluated by immunohistochemistry and
      immunofluorescence the prognostic value of the relative presence of CD133+ and
      CD133+/Ki67+ cells in patient tumors. RESULTS: In vitro CSC generation and the
      presence of > or = 2% CD133+ cells in tumor lesions negatively correlated with
      overall (P = 0.0001 and 0.02, respectively) and progression-free (P = 0.0002 and
      0.01, respectively) survival of patients. A very poor overall (P = 0.007) and
      progression-free (P = 0.001) survival was observed among patients whose tumors
      contained CD133+ cells expressing Ki67. Taking into account symptom duration,
      surgery type, age, O6-methylguanine-DNA methyltransferase promoter methylation,
      and p53 status, generation of CSCs and CD133/Ki67 coexpression emerged as highly
      significant independent prognostic factors, with an adjusted hazard ratio of 2.92
      (95% confidence interval, 1.37-6.2; P = 0.005) and 4.48 (95% confidence interval,
      1.68-11.9; P = 0.003), respectively. CONCLUSIONS: The analysis of CSCs may
      predict the survival of glioblastoma patients. In vitro CSC generation and
      presence of CD133+/Ki67+ cells are two considerable prognostic factors of disease
      progression and poor clinical outcome.

PMID- 19088038
TI  - Confirmation of gene expression-based prediction of survival in non-small cell
      lung cancer.
AB  - PURPOSE: It is a critical challenge to determine the risk of recurrence in early
      stage non-small cell lung cancer (NSCLC) patients. Accurate gene expression
      signatures are needed to classify patients into high- and low-risk groups to
      improve the selection of patients for adjuvant therapy. EXPERIMENTAL DESIGN:
      Multiple published microarray data sets were used to evaluate our previously
      identified lung cancer prognostic gene signature. Expression of the signature
      genes was further validated with real-time reverse transcription-PCR and Western
      blot assays of snap-frozen lung cancer tumor tissues. RESULTS: Our previously
      identified 35-gene signature stratified 264 patients with NSCLC into high- and
      low-risk groups with distinct overall survival rates (P < 0.05, Kaplan-Meier
      analysis, log-rank tests). The 35-gene signature further stratified patients with
      clinical stage 1A diseases into poor prognostic and good prognostic subgroups (P
      = 0.0007, Kaplan-Meier analysis, log-rank tests). This signature is independent
      of other prognostic factors for NSCLC, including age, sex, tumor differentiation,
      tumor grade, and tumor stage. The expression of the signature genes was validated
      with real-time reverse transcription-PCR analysis of lung cancer tumor specimens.
      Protein expression of two signature genes, TAL2 and ILF3, was confirmed in lung
      adenocarcinoma tumors by using Western blot analysis. These two biomarkers showed
      correlated mRNA and protein overexpression in lung cancer development and
      progression. CONCLUSIONS: The results indicate that the identified 35-gene
      signature is an accurate predictor of survival in NSCLC. It provides independent
      prognostic information in addition to traditional clinicopathologic criteria.

PMID- 19088039
TI  - Cyclooxygenase-2 expression is an independent predictor of poor prognosis in
      colon cancer.
AB  - PURPOSE: Cyclooxygenase-2 (COX-2; PTGS2) is considered to play an important role
      in colorectal carcinogenesis and is often up-regulated in colon cancers. However,
      previous data on the influence of COX-2 expression on patient outcome have been
      conflicting. EXPERIMENTAL DESIGN: Using 662 colon cancers (stage I-IV) in two
      independent prospective cohorts (the Nurses' Health Study and the Health
      Professionals Follow-up Study), we detected COX-2 overexpression in 548 (83%)
      tumors by immunohistochemistry. Cox proportional hazards models were used to
      compute hazard ratios (HR) of colon cancer-specific and overall mortalities,
      adjusted for patient characteristics and related molecular events, including the
      CpG island methylation phenotype, microsatellite instability, and p53, CIMP,
      KRAS, and BRAF mutations. RESULTS: During follow-up of the 662 cases, there were
      283 deaths, including 163 colon cancer-specific deaths. Patients with COX-2
      positive tumors showed a trend towards an inferior colon cancer-specific
      mortality [HR, 1.37; 95% confidence interval (95% CI), 0.87-2.14], which became
      significant after adjusting for tumor stage and other predictors of clinical
      outcome (multivariate HR, 1.70; 95% CI, 1.06-2.74; P = 0.029). Notably, the
      prognostic effect of COX-2 expression might differ according to p53 status
      (Pinteraction = 0.04). Compared with tumors with both COX-2 and p53 negative, COX
      2-positive tumors were significantly associated with an increased cancer-specific
      mortality (multivariate HR, 2.12; 95% CI, 1.23-3.65) regardless of p53 status. A
      similar trend was observed when overall mortality was used as an outcome.
      CONCLUSION: COX-2 overexpression is associated with worse survival among colon
      cancer patients. The effect of COX-2 on clinical outcome may be modified by p53
      status.

PMID- 19088040
TI  - The incidence, correlation with tumor-infiltrating inflammation, and prognosis of
      phosphorylated STAT3 expression in human gliomas.
AB  - PURPOSE: The signal transducer and activator of transcription 3 (STAT3) is
      frequently overexpressed in most cancers, propagates tumorigenesis, and is a key
      regulator of immune suppression in cancer patients. We sought to determine the
      incidence of phosphorylated STAT3 (p-STAT3) expression in malignant gliomas of
      different pathologic types, whether p-STAT3 expression is a negative prognostic
      factor, and whether p-STAT3 expression influences the inflammatory response
      within gliomas. METHODS: Using immunohistochemical analysis, we measured the
      incidence of p-STAT3 expression in 129 patients with gliomas of various
      pathologic types in a glioma tissue microarray. We categorized our results
      according to the total number of p-STAT3-expressing cells within the gliomas and
      correlated this number with the number of infiltrating T cells and T regulatory
      cells. We then evaluated the association between p-STAT3 expression and median
      survival time using univariate and multivariate analyses. RESULTS: We did not
      detect p-STAT3 expression in normal brain tissues or low-grade astrocytomas. We
      observed significant differences in the incidence of p-STAT3 expression between
      the different grades of astrocytomas and different pathologic glioma types. p
      STAT3 expression was associated with the population of tumor-infiltrating immune
      cells but not with that of T regulatory cells. On univariate analysis, we found
      that p-STAT3 expression within anaplastic astrocytomas was a negative prognostic
      factor. CONCLUSIONS: p-STAT3 expression is common within gliomas of both the
      astrocytic and oligodendroglial lineages and portends poor survival in patients
      with anaplastic astrocytomas. p-STAT3 expression differs significantly between
      gliomas of different pathologic types and grades and correlated with the degree
      of immune infiltration.

PMID- 19088041
TI  - Identification of PMF1 methylation in association with bladder cancer
      progression.
AB  - PURPOSE: Polyamines are important regulators of cell growth and death. The
      polyamine modulated factor-1 (PMF-1) is involved in polyamine homeostasis. After
      identifying an enriched CpG island encompassing the PMF1 promoter, we aimed at
      evaluating the clinical relevance of PMF1 methylation in bladder cancer.
      EXPERIMENTAL DESIGN: The epigenetic silencing of PMF1 by hypermethylation was
      tested in bladder cancer cells (n = 11) after azacytidine treatment. PMF1
      methylation status was evaluated in 507 bladder tumors and 118 urinary specimens
      of bladder cancer patients and controls. PMF1 protein expression was analyzed by
      immunohistochemistry on tissue arrays containing bladder tumors for which PMF1
      methylation was assessed (n = 218). RESULTS: PMF1 hypermethylation was associated
      with gene expression loss, being restored in vitro by a demethylating agent. An
      initial set of 101 primary frozen bladder tumors served to identify PMF1
      hypermethylation in 88.1% of the cases. An independent set of 406 paraffin
      embedded tumors also revealed a high PMF1 methylation rate (77.6%). PMF1
      methylation was significantly associated with increasing stage (P = 0.025).
      Immunohistochemical analyses revealed that PMF1 methylation was associated with
      cytoplasmic PMF1 expression loss (P = 0.032). PMF1 protein expression patterns
      were significantly associated with stage (P < 0.001), grade (P < 0.001), and poor
      overall survival using univariate (P < 0.001) and multivariate (P = 0.011)
      analyses. Moreover, PMF1 methylation in urinary specimens distinguished bladder
      cancer patients from controls (area under the curve = 0.800). CONCLUSION: PMF1
      was identified to be epigenetically modified in bladder cancer. The association
      of PMF1 methylation with tumor progression and its diagnostic ability using
      urinary specimens support including PMF1 assessment for the clinical management
      of bladder cancer patients.

PMID- 19088042
TI  - Molecular grading of ductal carcinoma in situ of the breast.
AB  - PURPOSE: Increased incidence of ductal carcinoma in situ (DCIS) associated with
      mammographic screening for breast cancer has emphasized the challenges of
      managing this condition. The aim of this study was to identify informative
      clinical indicators of DCIS biology by molecular profiling. EXPERIMENTAL DESIGN:
      Areas of in situ carcinoma, atypical ductal hyperplasia, and benign epithelium
      were microdissected from 46 invasive breast cancers. Oligonucleotide probes
      showing differential expression between DCIS associated with grade 1 and 3
      invasive cancer were identified by microarray-based gene expression profiling.
      Expression at these probes was used to define a "molecular grade"
      subcategorization of all samples. The genomic basis of molecular grade was
      examined by array-based comparative genomic hybridization. Clinical course was
      examined in a cohort of 134 patients with DCIS treated by surgery alone. RESULTS:
      DCIS samples were designated as low or high molecular grade based on expression
      at 173 probes. The low molecular grade subgroup included low (n = 10) and
      intermediate (n = 11) nuclear grade DCIS as well as all samples of atypical
      ductal hyperplasia (n = 4) and benign epithelium (n = 7). The high molecular
      grade subgroup included DCIS of intermediate (n = 7) and high (n = 19) nuclear
      grade. The character and degree of genomic aberration were distinct between
      molecular grade subgroups. A classification tree model including nuclear grade
      and Ki67 score accurately predicted molecular grade for 95.7% of samples. In an
      independent cohort, this showed a pattern of rapid disease recurrence for high
      molecular grade DCIS. CONCLUSIONS: Molecular profiling indicates a binary grading
      scheme for DCIS. This practical approach has potential to improve clinical
      evaluation of DCIS.

PMID- 19088043
TI  - Angiogenic switch of angiopietins-Tie2 system and its prognostic value in bladder
      cancer.
AB  - PURPOSE: Vascular endothelial growth factor (VEGF), angiopoietins (Ang-1 and Ang
      2), and their receptor Tie2 are critically involved in both normal and pathologic
      angiogenesis. The aim of this study was to explore the role of Ang-1, Ang-2,
      VEGF, and Tie2 in the development and progression of bladder cancer as well as to
      examine their prognostic value in this tumor type. EXPERIMENTAL DESIGN: Tumor
      samples of 113 bladder cancer patients, normal bladder epithelium of 5 noncancer
      patients, and two low-grade (UMUC3 and RT4) and two high-grade (J82 and T24)
      bladder cancer cell lines were analyzed by quantitative real-time PCR. The
      expression data were analyzed performing Wilcoxon rank-sum and Kaplan-Meier log
      rank tests as well as univariate Cox analyses and Cox proportional hazards
      regression model. RESULTS: In tissues of noninvasive bladder tumors, Ang-1
      expression was significantly lower (P < 0.001), whereas VEGF expression was
      significantly higher (P = 0.031) than in normal bladder tissue. These findings
      were also confirmed at the protein level by immunohistochemistry. In contrast,
      Tie2 and Ang-2 abundance in tumor did not differ significantly from that in
      normal bladder tissue. Multivariate analysis identified Ang-2 as a strong and
      independent predictor of tumor recurrence [hazard ratio (HR), 10.18; 95%
      confidence interval (95% CI), 2.69-38.49; P < 0.001] and Tie2 expression as an
      independent favorable prognostic factor for both metastasis (HR, 0.31; 95% CI,
      0.11-0.89; P = 0.029) and disease-specific survival (HR, 0.25; 95% CI, 0.10-0.62;
      P = 0.003). CONCLUSIONS: These data show the strongest change in expression of
      VEGF and Ang-1 in superficial bladder cancer in comparison with normal bladder
      epithelium and the invasive tumor stages. The prognostic significance of Ang-2
      and Tie2 underlines the essential role of angiopoietins-Tie2 system in
      progression of bladder cancer.

PMID- 19088044
TI  - Reversal of myeloid cell-mediated immunosuppression in patients with metastatic
      renal cell carcinoma.
AB  - PURPOSE: Tumor-induced immunosuppression remains a significant obstacle that
      limits the efficacy of biological therapy for renal cell carcinoma. Here we
      evaluate the role of CD33 myeloid-derived suppressor cells (MDSC) in the
      regulation of T-cell responses in renal cell carcinoma patients. We also examine
      effect of all-trans-retinoic acid (ATRA) on MDSC-mediated immune suppression.
      EXPERIMENTAL DESIGN: CD33-positive myeloid cells were isolated from the
      peripheral blood of renal cell carcinoma patients with magnetic beads and tested
      in vitro for their ability to inhibit T-cell responses. T-cell function was
      evaluated using ELISPOT and CTL assays. RESULTS: MDSC isolated from renal cell
      carcinoma patients, but not from healthy donors, were capable of suppressing
      antigen-specific T-cell responses in vitro through the secretion of reactive
      oxygen species and nitric oxide upon interaction with CTL. MDSC-mediated immune
      suppression and IFN-gamma down-regulation was reversible in vitro by exposing
      cells to the reactive oxygen species inhibitors. Moreover, ATRA was capable of
      abrogating MDSC-mediated immunosuppression and improving T-cell function by
      direct differentiation into antigen-presenting cell precursors. CONCLUSIONS:
      These results may have significant implications regarding the future design of
      active immunotherapy protocols that may include differentiation agents as part of
      a multimodal approach to renal cell carcinoma immunotherapy.

PMID- 19088045
TI  - Protein expression profiling in esophageal adenocarcinoma patients indicates
      association of heat-shock protein 27 expression and chemotherapy response.
AB  - PURPOSE: To identify pretherapeutic predictive biomarkers in tumor biopsies of
      patients with locally advanced esophageal adenocarcinomas treated with
      neoadjuvant chemotherapy, we used an explorative proteomic approach to correlate
      pretherapeutic protein expression profiles with tumor response to neoadjuvant
      chemotherapy. EXPERIMENTAL DESIGN: Thirty-four patients with locally advanced
      esophageal adenocarcinomas who received neoadjuvant platin/5-fluorouracil-based
      chemotherapy before surgical resection were enrolled in this study. Response to
      chemotherapy was determined (a) by the amount of decline of
      [18F]fluorodeoxyglucose tumor uptake 2 weeks after the start of chemotherapy
      measured by positron emission tomography and (b) by histopathologic evaluation of
      tumor regression after surgical resection. Explorative quantitative and
      qualitative protein expression analysis was done through a quantitative
      differential protein expression analysis that used dual-isotope radioactive
      labeling of protein extracts. Selected identified biomarkers were validated by
      immunohistochemistry and quantitative real time reverse transcription-PCR.
      RESULTS: Proteomic analysis revealed four cellular stress response-associated
      proteins [heat-shock protein (HSP) 27, HSP60, glucose-regulated protein (GRP) 94,
      GRP78] and a number of cytoskeletal proteins whose pretherapeutic abundance was
      significantly different (P < 0.001) between responders and nonresponders.
      Immunohistochemistry and gene expression analysis confirmed these data, showing a
      significant association between low HSP27 expression and nonresponse to
      neoadjuvant chemotherapy (P = 0.049 and P = 0.032, respectively). CONCLUSIONS:
      Albeit preliminary, our encouraging data suggest that protein expression
      profiling may distinguish cancers with a different response to chemotherapy. Our
      results suggest that response to chemotherapy may be related to a different
      activation of stress response and inflammatory biology in general. Moreover, the
      potential of HSPs and GRPs as biomarkers of chemotherapy response warrants
      further validation.

PMID- 19088046
TI  - A phase I and pharmacokinetic study of ixabepilone in combination with
      Carboplatin in patients with advanced solid malignancies.
AB  - PURPOSE: To determine the recommended phase II dose of combination ixabepilone
      plus carboplatin based on the maximum tolerated dose, pharmacokinetics, optimum
      schedule, and safety. EXPERIMENTAL DESIGN: Patients with advanced solid
      malignancies were treated with escalating doses of carboplatin plus ixabepilone
      administered on day 1 (schedule A) or days 1 and 8 (schedule B) of a 21-day
      cycle. Blood was sampled during cycle 1 for pharmacokinetic analysis of
      ixabepilone (both schedules) and carboplatin (schedule B). RESULTS: Fifty-two
      patients were treated with ixabepilone doses ranging from 30 to 50 mg/m2 per 21
      day cycle plus carboplatin area under curve (AUC) 5 or 6 (Calvert formula). On
      schedule A (ixabepilone 40 mg/m2 over 1 hour plus carboplatin AUC 6), 2 of 2
      patients experienced dose-limiting toxicity (DLT). On schedule B (ixabepilone 25
      mg/m2 over 1 hour on days 1 and 8 plus carboplatin AUC 6), 3 of 3 patients
      experienced DLT. DLT was myelosuppression; however, cumulative sensory neuropathy
      limited extended dosing on schedule A. Ixabepilone and carboplatin
      pharmacokinetics were similar to those using either drug as monotherapy,
      indicating an absence of pharmacokinetic drug interactions. Based on DLTs and
      tolerability with repeated dosing, the recommended doses were 30 mg/m2
      ixabepilone (1-hour infusion) d1 q3w plus carboplatin AUC 6 (schedule A) and 20
      mg/m2 ixabepilone (1 hour infusion) d1, d8 q3w plus carboplatin AUC 6 (schedule
      B). CONCLUSIONS: Data from the present study show the feasibility and
      tolerability of combination ixabepilone plus carboplatin, with ixabepilone
      administered on day 1 or on days 1 and 8 on a 21-day cycle.

PMID- 19088047
TI  - A phase I study of the pan bcl-2 family inhibitor obatoclax mesylate in patients
      with advanced hematologic malignancies.
AB  - PURPOSE: The outcome of patients with refractory leukemia and myelodysplasia is
      poor, and new therapies are needed. The antiapoptotic proteins of the Bcl-2
      family are overexpressed in these malignancies and are potential therapeutic
      targets. Therefore, we conducted a phase I clinical trial of the small-molecule
      pan-Bcl-2 inhibitor, obatoclax mesylate, in patients with refractory leukemia and
      myelodysplasia to assess its safety and define its optimal dose. EXPERIMENTAL
      DESIGN: Forty-four patients with refractory leukemia or myelodysplasia were
      treated with obatoclax mesylate by continuous intravenous infusion at increasing
      doses and frequencies. RESULTS: A total of 306 infusions of obatoclax mesylate
      were administered with a median of 5 infusions per patient. The study drug was
      well tolerated up to the highest dose planned without dose-limiting toxicity.
      Grade 1/2 central nervous system symptoms were the most common adverse events
      attributable to the study drug. One patient with acute myeloid leukemia with
      mixed lineage leukemia t(9;11) rearrangement achieved a complete remission, which
      lasted 8 months. Three of 14 patients with myelodysplasia showed hematologic
      improvement with RBC or platelet transfusion independence. CONCLUSIONS: Obatoclax
      mesylate is well tolerated and these results support its further investigation in
      patients with leukemia and myelodysplasia.

PMID- 19088048
TI  - Phase II trial of 17-allylamino-17-demethoxygeldanamycin in patients with
      metastatic melanoma.
AB  - PURPOSE: Activation of the mitogen-activated protein kinase (MAPK) pathway and
      the phosphatidylinositol 3-kinase/AKT pathway seems to be critical for melanoma
      proliferation. Components of these pathways are client proteins of heat-shock
      protein 90 (hsp90), suggesting that inhibition of hsp90 could have significant
      antimelanoma effects. We conducted a phase II trial using the hsp90 inhibitor 17
      allylamino-17-demethoxygeldanamycin (17-AAG) in melanoma patients. The primary
      end points were clinical responses and whether treatment inhibited MAPK pathway
      activity. EXPERIMENTAL DESIGN: Melanoma patients with measurable disease were
      stratified on the basis of whether or not their tumor harbored a V600E BRAF
      mutation. The hsp90 inhibitor 17-AAG was administered i.v. once weekly x 6 weeks
      at 450 mg/m2. Tumor biopsies were obtained pretreatment and 18 to 50 hours after
      the first dose of 17-AAG, and were snap-frozen. RESULTS: Fifteen evaluable
      patients were treated; nine had BRAF mutations and six were wild-type. No
      objective responses were observed. Western blot analysis of tumor biopsies showed
      an increase in hsp70 and a decrease in cyclin D1 expression in the posttreatment
      biopsies but no significant effect on RAF kinases or phospho-extracellular signal
      regulated kinase expression. Plasma analyzed by mutant-specific PCR for V600E
      BRAF showed 86% sensitivity and 67% specificity in predicting tumor DNA
      sequencing results. CONCLUSIONS: At this dose and schedule of 17-AAG, the effects
      of 17-AAG on RAF kinase expression were short-lived, and no objective
      antimelanoma responses were seen. Future trials in melanoma should focus on a
      more potent hsp90 inhibitor or a formulation that can be administered chronically
      for a more prolonged suppression of the MAPK pathway.

PMID- 19088049
TI  - Effect of cigarette smoking on imatinib in patients in the soft tissue and bone
      sarcoma group of the EORTC.
AB  - PURPOSE: Smoking is a potent inducer of cytochrome P450 (CYP) 1A2 and may affect
      the pharmacokinetics of CYP1A2 metabolized drugs. The effect of smoking on the
      pharmacokinetics of imatinib, which is metabolized by CYP3A4 and partly by
      CYP1A2, is unknown. We studied the effect of smoking on imatinib
      pharmacokinetics, safety, and efficacy. EXPERIMENTAL DESIGN: Imatinib
      pharmacokinetics, safety, and efficacy was analyzed in 45 patients with
      gastrointestinal stromal tumors (GIST) or soft-tissue sarcoma included in two
      European Organisation for Research and Treatment of Cancer Soft Tissue and Bone
      Sarcoma Group trials, including 15 smokers and 30 nonsmokers. Apparent oral
      clearance, distribution volume, elimination half-life, and dose-standardized area
      under the concentration curve (AUC) were assessed in 34 patients using nonlinear
      mixed-effect modeling. RESULTS: Mean +/- SD pharmacokinetic variables in smokers
      (n = 9) versus nonsmokers (n = 25) groups were 9.6 +/- 5.5 versus 9.2 +/- 4.6 L/h
      (apparent oral clearance), 216.5 +/- 114.3 versus 207.0 +/- 116.9 L (distribution
      volume), 16.1 +/- 6.0 versus 16.5 +/- 6.0 h (elimination half-life), and 133.6 +/
      71.0 versus 142.3 +/- 84.0 ng h/mL mg area under the concentration curve; P >
      0.05. Smokers experienced more grade 2/3 anemia (P = 0.010) and fatigue (P =
      0.011) and those with GIST had a significantly shorter overall survival (P =
      0.037) and time to progression (P = 0.052). CONCLUSIONS: This retrospective study
      suggests that the pharmacokinetics of imatinib is not affected by smoking.
      However, smokers have an increased risk of anemia and fatigue. Smokers with GIST
      have a shorter overall survival and time to progression.

PMID- 19088050
TI  - Effects of high-dose IFNalpha2b on regional lymph node metastases of human
      melanoma: modulation of STAT5, FOXP3, and IL-17.
AB  - PURPOSE: Signal transducer and activator of transcription 5 (STAT5) and STAT3
      oppose one another in regulation of the reciprocal development of CD4+CD25+FOXP3+
      regulatory T cells (Treg) and T helper 17 (Th17). A reduction in STAT3 is
      associated with up-regulation of Treg, and STAT5 activation promotes Treg
      differentiation or function while constraining Th17 generation. The effects of
      IFNalpha on STAT signaling in relation to tumor tissue Treg and Th17 have not
      been documented in humans beyond the observations that IFNalpha2b down-regulates
      STAT3. EXPERIMENTAL DESIGN: Following diagnostic biopsy and before definitive
      surgery, 20 doses of high-dose IFNalpha2b (HDI) were administered to patients
      with stage IIIB melanoma who gave written informed consent. Lymph node biopsies,
      in which both total STAT3 and phosphorylated STAT3 were down-regulated by HDI,
      were probed with STAT5, FOXP3, CD4, and interleukin 17 (IL-17) with
      immunohistochemistry and/or immunofluorescence techniques. RESULTS: The
      percentage of FOXP3+ lymphocytes determined by immunohistochemistry was up
      regulated from 3.06 +/- 0.65% to 9.86 +/- 1.27% (n = 13, P = 0.0002), and this
      observation was confirmed by immunofluorescence evaluation of CD4+FOXP3+ Tregs.
      HDI induced STAT5 up-regulation (five cases observed) in melanoma cells and
      lymphocytes but did not induce the generation of IL-17-expressing lymphocytes.
      Increased STAT5 expression was associated with increased FOXP3 expression among
      lymphocytes, and STAT5 was constitutively activated among both melanoma cells and
      lymphocytes. CONCLUSION: IFNalpha2b up-regulates STAT5 and down-regulates STAT3,
      in conjunction with up-regulation of Treg and inhibition of IL-17-expressing
      lymphocytes in melanoma tissues. These findings suggest that the effects of
      IFNalpha may be potentiated through interference with the response of Tregs
      and/or STAT5.

PMID- 19088052
TI  - Clinical characterization might help in preventing osteonecrosis of the jaw.

PMID- 19088054
TI  - Varus alignment leads to increased forces in the anterior cruciate ligament.
AB  - BACKGROUND: Varus thrust of the knee is a dynamic increase of an often
      preexisting varus angle and it is suspected to be a major reason for failure of
      anterior cruciate ligament reconstructions. However, it is not known if a direct
      relationship exists between varus thrust and forces in the anterior cruciate
      ligament. HYPOTHESIS: Forces in the anterior cruciate ligament increase with
      increasing varus alignment, and consequently an anterior cruciate ligament
      deficiency in a varus-aligned leg leads to more lateral tibiofemoral joint
      opening. STUDY DESIGN: Controlled laboratory study. METHODS: Six human cadaver
      legs were axially loaded with 3 different weightbearing lines--a neutral
      weightbearing line, a weightbearing line that passes through the middle of the
      medial tibial plateau (50% varus), and a line passing the edge of the medial
      tibial plateau (100% varus)--that were used to create a varus moment. The
      resulting lateral tibiofemoral joint opening and corresponding anterior cruciate
      ligament tension were measured. The tests were repeated with and without the
      anterior cruciate ligament in place. RESULTS: In the neutral aligned legs, there
      was no apparent lateral joint opening, and no anterior cruciate ligament tension
      change was noted. The lateral joint opening increased when the weightbearing line
      increased from 0% to 50% to 100%. The lateral joint opening was significantly
      higher in 10 degrees of knee flexion compared with knee extension. In the 100%
      varus weightbearing line, the anterior cruciate ligament tension was
      significantly higher (53.9 N) compared with neutral (31 N) or the 50%
      weightbearing line (37.9 N). A thrust could only be observed in the 100%
      weightbearing line tests. In the absence of an anterior cruciate ligament, there
      was more lateral joint opening, although this was only significant in the 100%
      weightbearing line. CONCLUSION: There is a direct relationship between varus
      alignment and anterior cruciate ligament tension. In the absence of an anterior
      cruciate ligament, the amount of lateral opening tends to increase. With
      increasing lateral opening, a thrust can sometimes be experimentally observed.
      CLINICAL RELEVANCE: A varus alignment in an anterior cruciate ligament-deficient
      knee does not necessarily lead to a varus thrust and therefore does not always
      need operative varus alignment correction. However, in an unstable anterior
      cruciate ligament-deficient knee with a varus thrust, it might be safer to
      perform a high valgus tibial osteotomy to minimize the risk of an anterior
      cruciate ligament reconstruction failure.

PMID- 19088055
TI  - Differences in ankle range of motion before and after exercise in 2 tape
      conditions.
AB  - BACKGROUND: Athletic tape has been used on the ankle to decrease range of motion
      and to prevent injuries. Results from previous research found that with physical
      exercise athletic tape loses some of its restricting properties; recently, a new
      self-adherent taping product was developed that may restrict range of motion
      regardless of exercise. HYPOTHESIS: Self-adherent tape will maintain ankle range
      of motion restriction more than traditional white cloth tape both before and
      after activity. STUDY DESIGN: Controlled laboratory study. METHODS: Twenty
      volunteers participated in testing procedures on 3 separate days, 1 for each
      taping condition (self-adherent, white cloth, and no tape). The participant's
      ankle range of motion was measured with an electrogoniometer before application
      of the tape, immediately after application of the tape, and after 30 minutes of
      physical exercise. Range of motion was measured in 2 planes of motion: inversion
      to eversion and dorsiflexion to plantar flexion. RESULTS: White cloth tape and
      self-adherent tape both restricted inversion to eversion range of motion
      immediately after application, but with 30 minutes of exercise only the self
      adherent tape maintained the decreased range of motion. For dorsiflexion to
      plantar flexion range of motion, the white tape and self-adherent tape both
      significantly decreased range of motion immediately after application and after
      the exercise protocol. CONCLUSIONS AND CLINICAL RELEVANCE: The self-adherent tape
      maintained range of motion restriction both before and after exercise.
      Conversely, the white cloth tape lost some of its restrictive properties after 30
      minutes of exercise.

PMID- 19088057
TI  - Eccentric loading versus eccentric loading plus shock-wave treatment for
      midportion achilles tendinopathy: a randomized controlled trial.
AB  - BACKGROUND: Results of a previous randomized controlled trial have shown
      comparable effectiveness of a standardized eccentric loading training and of
      repetitive low-energy shock-wave treatment (SWT) in patients suffering from
      chronic midportion Achilles tendinopathy. No randomized controlled trials have
      tested whether a combined approach might lead to even better results. PURPOSE: To
      compare the effectiveness of 2 management strategies--group 1: eccentric loading
      and group 2: eccentric loading plus repetitive low-energy shock-wave therapy.
      STUDY DESIGN: Randomized controlled trial; Level of evidence, 1. METHODS: Sixty
      eight patients with a chronic recalcitrant (>6 months) noninsertional Achilles
      tendinopathy were enrolled in a randomized controlled study. All patients had
      received unsuccessful management for >3 months, including at least (1)
      peritendinous local injections, (2) nonsteroidal anti-inflammatory drugs, and (3)
      physiotherapy. A computerized random-number generator was used to draw up an
      allocation schedule. Analysis was on an intention-to-treat basis. RESULTS: At 4
      months from baseline, the VISA-A score increased in both groups, from 50 to 73
      points in group 1 (eccentric loading) and from 51 to 87 points in group 2
      (eccentric loading plus shock-wave treatment). Pain rating decreased in both
      groups, from 7 to 4 points in group 1 and from 7 to 2 points in group 2. Nineteen
      of 34 patients in group 1 (56%) and 28 of 34 patients in group 2 (82%) reported a
      Likert scale of 1 or 2 points ("completely recovered" or "much improved"). For
      all outcome measures, groups 1 and 2 differed significantly in favor of the
      combined approach at the 4-month follow-up. At 1 year from baseline, there was no
      difference any longer, with 15 failed patients of group 1 opting for having the
      combined therapy as cross-over and with 6 failed patients of group 2 having
      undergone surgery. CONCLUSION: At 4-month follow-up, eccentric loading alone was
      less effective when compared with a combination of eccentric loading and
      repetitive low-energy shock-wave treatment.

PMID- 19088056
TI  - Posterolateral structures of the knee in posterior cruciate ligament deficiency.
AB  - BACKGROUND: In vitro data suggest that injury to the posterior cruciate ligament
      stresses the posterolateral structures of the knee, placing them at greater risk
      of secondary injury. However, it is not known how isolated posterior cruciate
      ligament deficiency affects these soft tissue stabilizers of the knee joint in
      vivo. HYPOTHESIS: Posterior cruciate ligament deficiency will alter the apparent
      length patterns of the lateral collateral ligament (LCL) and popliteus. STUDY
      DESIGN: Controlled laboratory study. METHODS: The apparent length changes in the
      lateral collateral ligament and popliteus muscle-tendon unit during weightbearing
      knee flexion were studied in 14 patients with isolated, unilateral posterior
      cruciate ligament deficiency using magnetic resonance imaging, dual-orthogonal
      fluoroscopy, and 3-dimensional modeling. Data of the injured and uninjured
      contralateral sides were compared. RESULTS: Posterior cruciate ligament
      deficiency caused significant increases in the apparent length of both
      posterolateral structures (P < .05). The differences between injured and
      uninjured contralateral side were greatest at 120 degrees of knee flexion in the
      lateral collateral ligament (48.2 +/- 6.1 mm and 51.6 +/- 6.1 mm, respectively)
      and at 30 degrees of knee flexion in the popliteus (101.2 +/- 9.3 mm and 110.4 +/
      10.2 mm, respectively). CONCLUSION: Deficiency of the posterior cruciate
      ligament alters the length patterns of posterolateral structures in vivo and
      might place them at greater risk of secondary injury. CLINICAL RELEVANCE:
      Reestablishment of normal kinematics after posterior cruciate ligament injury is
      critical for restoring normal function of posterolateral structures of the knee.

PMID- 19088058
TI  - Numerical/experimental analysis of the stress field around miniscrews for
      orthodontic anchorage.
AB  - The aims of this study were to analyse the stress distribution developing around
      an orthodontic miniscrew (OM) inserted into the maxilla and to determine the
      stress field changes for different screw lengths and for different levels of
      osseointegration occurring at the bone/screw interface. An integrated
      experimental/numerical approach was adopted. Using the photoelastic technique,
      the stress field arising in the bone after screw insertion and the application of
      the initial orthodontic load was assessed. The finite element (FE) method was
      used to determine the stress acting in the bony tissue after a given time
      following screw application, when, for the viscoelastic relaxation effects, the
      only stress field remaining was that due to the application of the orthodontic
      load. Different levels of osseointegration were hypothesized. Photoelastic
      analyses showed that stress distribution does not change significantly for
      moderate initial orthodontic loads. From the FE simulations, it was found that
      critical conditions occur for screws 14 mm long with an orthodontic load of 2 N.
      The optimal screw length seems to be 9 mm. For such a dimension, small stress
      values were found as well as low risk of lesion to the anatomical structures.

PMID- 19088059
TI  - Pain intensity during the first 7 days following the application of light and
      heavy continuous forces.
AB  - The purpose of the present study was to determine whether a force of 20 cN can be
      biologically active for tooth movement and to examine the pain intensity during
      the application of light (20 cN) or heavy (200 cN) continuous forces for 7 days.
      In the first experiment, a force of 20 cN was applied to eight canines in five
      volunteers. The mean tooth movement during 10 weeks was 2.4 mm. In the second
      experiment, two forces of 20 or 200 cN were applied to maxillary premolars in 12
      male subjects (aged 24-31 years) to measure pain intensity for 7 days.
      Spontaneous and biting pain were recorded every 2-4 hours on a 100 mm visual
      analogue scale (VAS). Wilcoxon signed-rank test was used for statistical
      analysis. Comparing the VAS score at force initiation with the other time points,
      there was no significant difference in spontaneous pain for either group, or in
      biting pain for the light-force group. However, biting pain in the heavy-force
      group during the time period from 6 to 156 hours was significantly (P < 0.05)
      greater than that at force initiation. Comparing the VAS scores between the light
      and heavy-force group, VAS scores for biting pain in the heavy-force group
      during the time period from 8 to 100 hours was significantly (P < 0.05) greater
      than that in the light-force group. A force of 20 cN can move teeth, but pain
      intensity while biting may be greater approximately 8 hours to 5 days following
      the application of heavy continuous force compared with light force.

PMID- 19088060
TI  - Elevated non-specific immunity and normal Listeria clearance in young and old
      vitamin D receptor knockout mice.
AB  - 1,25-dihydroxyvitamin D(3) [1,25(OH)(2)D(3)] and the vitamin D receptor (VDR) are
      important regulators of autoimmunity. The effect of the VDR on the ability of
      mice to fight a primary or secondary infection has not been determined. Young and
      old VDR knockout (KO) mice were able to clear both primary and secondary
      infections with Listeria monocytogenes. However, the kinetics of clearance was
      somewhat delayed in the absence of the VDR. Memory T cell development was not
      different in young VDR KO and wild-type (WT) mice; however, old VDR KO mice had
      significantly less memory T cells than their WT counterparts but still mounted an
      adequate immune response as determined by the complete clearance of L.
      monocytogenes. Although the primary and secondary immune responses were largely
      intact in the VDR KO mice, the old VDR KO mice had increased cytokines and
      antibody responses compared with the old WT mice. In particular, old VDR KO mice
      had elevated antigen non-specific antibodies; however, these magnified immune
      responses did not correspond to more effective Listeria clearance. The increased
      antibody and cytokine responses in the old VDR KO mice are consistent with the
      increased susceptibility of these mice to autoimmunity.

PMID- 19088061
TI  - IL-23 modulates CD56+/CD3- NK cell and CD56+/CD3+ NK-like T cell function
      differentially from IL-12.
AB  - NK and NK-like T cells play an essential role in linking innate and adaptive
      immunity through their ability to secrete IFN-gamma. The exact trigger initiating
      production of IFN-gamma is uncertain. Antigen-presenting cell (APC)-derived IL-12
      is thought to be the classical IFN-gamma-inducing cytokine but requires an
      additional stimulus such as IFN-gamma itself. IL-23 and IL-18 are among the first
      cytokines secreted by APC in response to binding of pathogen-associated molecular
      patterns such as LPS. Thus, early APC-derived IL-23 may be an initial trigger of
      IFN-gamma production in NK and NK-like T cells. Herein, we characterized the
      effect of IL-23 on IFN-gamma secretion by NK and NK-like T cells. Our findings
      show that IL-23 and IL-18 synergistically elicit IFN-gamma production in NK-like
      T cells but not in NK cells. In contrast, IL-12 together with IL-18-induced
      secretion of IFN-gamma in both populations. The observed synergy between IL-23
      and IL-18 in NK-like T cells coincided with IL-23-mediated up-regulation of IL
      18Ralpha. Furthermore, IL-23 up-regulated CD56 expression in NK-like T cells and,
      together with IL-18, induced proliferation of NK and NK-like T cells. We
      postulate a role for APC-derived IL-23 in the activation of NK and NK-like T
      cells early in infection and in shaping T(h)1 differentiation, via induction of
      IFN-gamma, which provides the additional stimulus needed for APC to subsequently
      produce IL-12.

PMID- 19088062
TI  - CD8beta knockout mice mount normal anti-viral CD8+ T cell responses--but why?
AB  - It has been shown previously that CD8beta in vitro increases the range and the
      sensitivity of antigen recognition and in vivo plays an important role in the
      thymic selection of CD8+ T cells. Consistent with this, we report here that CD8+
      T cells from CD8beta knockout (KO) P14 TCR transgenic mice proliferate
      inefficiently in vitro. In contrast to these findings, we also show that CD8beta
      KO mice mount normal CD8 primary, secondary and memory responses to acute
      infection with lymphocytic choriomeningitis virus. Tetramer staining and
      cytotoxic experiments revealed a predominance of CD8-independent CTL in CD8beta
      KO mice. The TCR repertoire, especially the one of the TCRalpha chain, was
      different in CD8beta KO mice as compared with B6 mice. Our results indicate that
      in the absence of CD8beta, CD8-independent TCRs are preferentially selected,
      which in vivo effectively compensates for the reduced co-receptor function of
      CD8alphaalpha.

PMID- 19088063
TI  - Could the lower frequency of CD8+CD18+CD45RO+ lymphocytes be biomarkers of human
      VL?
AB  - Toward obtaining a more comprehensive understanding of factors governing
      activation and/or function during visceral leishmaniasis (VL), we have compared
      active disease (pre-treatment) versus post-chemotherapy immune response in VL
      patients by means of ex vivo staining with different cell markers. Our results
      show that during active disease, the frequency of T cells positive for CD25, CTLA
      4 and CD45RO was significantly lower in VL patients compared with healthy
      controls, whereas cells staining positive for Annexin V and CD95 were
      significantly higher. In all cases, chemotherapy was able to restore these
      frequencies to normal levels. Interestingly, significant differences in the
      frequency of CD18 and in the frequency of CD45RO-positive cells were observed in
      the CD8+ T cell subset. These two frequencies were also significantly higher in
      bone marrow when compared with peripheral blood, suggesting a possible
      compartmentalization of certain CD8+ T cell populations during active disease.
      Given that CD8+ T cells have been shown to play an essential role in immunity to
      infection with Leishmania, our data indicate that the lower frequency of CD18+
      and CD45RO+ lymphocytes in the bone marrow CD8+ T cell subset may be considered a
      biomarker of acute VL.

PMID- 19088064
TI  - Defects in Jak-STAT-mediated cytokine signals cause hyper-IgE syndrome: lessons
      from a primary immunodeficiency.
AB  - Hyper-IgE syndrome (HIES) is a primary immunodeficiency characterized by atopic
      manifestations and susceptibility to infections with extracellular bacteria and
      fungi, which frequently occur in the skin and lung. Atopic manifestations in HIES
      include extremely high serum IgE levels, eczema and eosinophilia. Most of the
      extracellular bacterial infections are associated with disproportionally milder
      inflammation than normal, which was originally described as having a 'cold
      abscess'. Non-immunological abnormalities are also observed in most patients with
      HIES, including a distinctive facial appearance, scoliosis, hyper-extensive
      joints and retained primary teeth. Recent studies have demonstrated that
      hypomorphic mutations in signal transducer and activator of transcription 3
      result in the classical multisystem form of HIES, whereas a null mutation in
      tyrosine kinase 2 causes the autosomal recessive form of HIES that is associated
      with viral and mycobacterial infections. Analyses of cytokine responses in both
      types of HIES have revealed defects in signal transduction for multiple cytokines
      including IL-6 and IL-23, leading to impaired T(h)17 function. These results
      suggest that the defect in multiple cytokine signals is the molecular basis of
      the immunological and non-immunological abnormalities in HIES and that the
      susceptibility to infections with extracellular bacteria and fungi in HIES might
      be associated with the defect in T(h)17 cell differentiation.

PMID- 19088065
TI  - Differential N-glycosylation of kallikrein 6 derived from ovarian cancer cells or
      the central nervous system.
AB  - Ovarian cancer causes more deaths than any other gynecological disorder.
      Perturbed glycosylation is one of the hallmarks of this malignancy. Kallikrein 6
      (KLK6) elevation in serum is a diagnostic and prognostic indicator in ovarian
      cancer. The majority of ovarian carcinomas express high levels of KLK6, which
      diffuses into the circulation. Under physiological conditions, KLK6 is expressed
      highly in the central nervous system and found at high levels in cerebrospinal
      fluid from where it enters the circulation. Our aim was to characterize and
      compare the N-glycosylation status of this protein in ovarian cancer ascites
      fluid and cerebrospinal fluid. Anion-exchange chromatography was used to reveal
      different post-translational modifications on the two isoforms. Mobility gel
      shift Western blot analysis coupled with glycosidase digestion showed that the
      molecular weight difference between the two isoforms was because of differential
      glycosylation patterns. The presence of a single N-glycosylation site on KLK6 was
      confirmed by site-directed mutagenesis. Using a Sambucus nigra agglutinin
      monoclonal antibody sandwich enzyme-linked immunosorbent assay approach, it was
      shown that ovarian cancer-derived KLK6 was modified with alpha2-6-linked sialic
      acid. The structure and composition of glycans of both KLK6 isoforms was
      elucidated by glycopeptide monitoring with electrospray ionization-Orbitrap
      tandem mass spectrometry. Therefore, the extensive and almost exclusive
      sialylation of KLK6 from ovarian cancer cells could lead to the development of an
      improved biomarker for the early diagnosis of ovarian carcinoma.

PMID- 19088066
TI  - High-content functional screen to identify proteins that correct F508del-CFTR
      function.
AB  - Cystic Fibrosis is caused by mutations in CFTR, with a deletion of a
      phenylalanine at position 508 (F508del-CFTR) representing the most common
      mutation. The F508del-CFTR protein exhibits a trafficking defect and is retained
      in the endoplasmic reticulum. Here we describe the development of a high-content
      screen based on a functional assay to identify proteins that correct the F508del
      CFTR defect. Using a HEK293 MSR GripTite cell line that stably expresses F508del
      CFTR, we individually co-expressed approximately 450 unique proteins fused to the
      Cl(-)-sensitive YFP(H148Q/I152L) mutant. We then tested correction of F508del
      CFTR function by the CI(-)/l(-) exchange method following stimulation with
      forskolin/IBMX/genistein, using quantitative recordings in multiple individual
      cells with a high-content (high-throughput) Cellomics KSR imaging system. Using
      this approach, we identified several known and novel proteins that corrected
      F508del-CFTR function, including STAT1, Endothelin 1, HspA4, SAPK substrate
      protein 1, AP2M1, LGALS3/galectin-3, Trk-fused gene, Caveolin 2, PAP/REG3alpha,
      and others. The ability of these correctors to rescue F508del-CFTR trafficking
      was then validated by demonstrating their enhancement of maturation (appearance
      of band C) and by cell surface expression of F508del-CFTR bearing HA tag at the
      ectodomain using confocal microscopy and flow cytometry. These data demonstrate
      the utility of high-content analyses for identifying proteins that correct mutant
      CFTR and discover new proteins that stimulate this correction. This assay can
      also be utilized for RNAi screens to identify inhibitory proteins that block
      correction of F508del-CFTR, small molecule, and peptide screens.

PMID- 19088067
TI  - Activity, splice variants, conserved peptide motifs, and phylogeny of two new
      alpha1,3-fucosyltransferase families (FUT10 and FUT11).
AB  - We report the cloning of three splice variants of the FUT10 gene, encoding for
      active alpha-l-fucosyltransferase-isoforms of 391, 419, and 479 amino acids, and
      two splice variants of the FUT11 gene, encoding for two related alpha-l
      fucosyltransferases of 476 and 492 amino acids. The FUT10 and FUT11 appeared 830
      million years ago, whereas the other alpha1,3-fucosyltransferases emerged 450
      million years ago. FUT10-391 and FUT10-419 were expressed in human embryos,
      whereas FUT10-479 was cloned from adult brain and was not found in embryos.
      Recombinant FUT10-419 and FUT10-479 have a type II trans-membrane topology and
      are retained in the endoplasmic reticulum (ER) by a membrane retention signal at
      their NH(2) termini. The FUT10-479 has, in addition, a COOH-ER membrane retention
      signal. The FUT10-391 is a soluble protein without a trans-membrane domain or ER
      retention signal that transiently localizes to the Golgi and then is routed to
      the lysosome. After transfection in COS7 cells, the three FUT10s and at least one
      FUT11, link alpha-l-fucose onto conalbumin glycopeptides and biantennary N-glycan
      acceptors but not onto short lactosaminyl acceptor substrates as do classical
      monoexonic alpha1,3-fucosyltransferases. Modifications of the innermost core
      GlcNAc of the N-glycan, by substitution with ManNAc or with an opened GlcNAc ring
      or by the addition of an alpha1,6-fucose, suggest that the FUT10 transfer is
      performed on the innermost GlcNAc of the core chitobiose. We can exclude alpha1,3
      fucosylation of the two peripheral GlcNAcs linked to the trimannosyl core of the
      acceptor, because the FUT10 fucosylated biantennary N-glycan product loses both
      terminal GlcNAc residues after digestion with human placenta alpha-N
      acetylglucosaminidase.

PMID- 19088069
TI  - Mechanistic insights into the hydrolysis and synthesis of ceramide by neutral
      ceramidase.
AB  - Ceramidase (CDase; EC 3.5.1.23) hydrolyzes ceramide to generate sphingosine and
      fatty acid. The enzyme plays a regulatory role in a variety of physiological
      events in eukaryotes and also functions as an exotoxin in particular bacteria.
      The crystal structures of neutral CDase from Pseudomonas aeruginosa (PaCD) in the
      C2-ceramide-bound and -unbound forms were determined at 2.2 and 1.4 A
      resolutions, respectively. PaCD consists of two domains, and the Zn(2+)- and
      Mg(2+)/Ca(2+)-binding sites are found within the center of the N-terminal domain
      and the interface between the domains, respectively. The structural comparison
      between the C2-ceramide-bound and unbound forms revealed an open-closed
      conformational change occurring to loop I upon binding of C2-ceramide. In the
      closed state, this loop sits above the Zn(2+) coordination site and over the
      opening to the substrate binding site. Mutational analyses of residues
      surrounding the Zn(2+) of PaCD and rat neutral CDase revealed that the cleavage
      or creation of the N-acyl linkage of ceramide follows a similar mechanism as
      observed for the Zn(2+)-dependent carboxypeptidases. The results provide an
      understanding of the molecular mechanism of hydrolysis and synthesis of ceramide
      by the enzyme. Furthermore, insights into the actions of PaCD and eukaryotic
      neutral CDases as an exotoxin and mediators of sphingolipid signaling are also
      revealed, respectively.

PMID- 19088068
TI  - N terminus of Swr1 binds to histone H2AZ and provides a platform for subunit
      assembly in the chromatin remodeling complex.
AB  - Variant histone H2AZ-containing nucleosomes are involved in the regulation of
      gene expression. In Saccharomyces cerevisiae, chromatin deposition of histone
      H2AZ is mediated by the fourteen-subunit SWR1 complex, which catalyzes ATP
      dependent exchange of nucleosomal histone H2A for H2AZ. Previous work defined the
      role of seven SWR1 subunits (Swr1 ATPase, Swc2, Swc3, Arp6, Swc5, Yaf9, and Swc6)
      in maintaining complex integrity and H2AZ histone replacement activity. Here we
      examined the function of three additional SWR1 subunits, bromodomain containing
      Bdf1, actin-related protein Arp4 and Swc7, by analyzing affinity-purified mutant
      SWR1 complexes. We observed that depletion of Arp4 (arp4-td) substantially
      impaired the association of Bdf1, Yaf9, and Swc4. In contrast, loss of either
      Bdf1 or Swc7 had minimal effects on overall complex integrity. Furthermore, the
      basic H2AZ histone replacement activity of SWR1 in vitro required Arp4, but not
      Bdf1 or Swc7. Thus, three out of fourteen SWR1 subunits, Bdf1, Swc7, and
      previously noted Swc3, appear to have roles auxiliary to the basic histone
      replacement activity. The N-terminal region of the Swr1 ATPase subunit is
      necessary and sufficient to direct association of Bdf1 and Swc7, as well as Arp4,
      Act1, Yaf9 and Swc4. This same region contains an additional H2AZ-H2B specific
      binding site, distinct from the previously identified Swc2 subunit. These
      findings suggest that one SWR1 enzyme might be capable of binding two H2AZ-H2B
      dimers, and provide further insight on the hierarchy and interdependency of
      molecular interactions within the SWR1 complex.

PMID- 19088070
TI  - Identification of a gatekeeper residue that prevents dehydrogenases from acting
      as oxidases.
AB  - The oxygen reactivity of flavoproteins is poorly understood. Here we show that a
      single Ala to Gly substitution in l-galactono-gamma-lactone dehydrogenase (GALDH)
      turns the enzyme into a catalytically competent oxidase. GALDH is an
      aldonolactone oxidoreductase with a vanillyl-alcohol oxidase (VAO) fold. We found
      that nearly all oxidases in the VAO family contain either a Gly or a Pro at a
      structurally conserved position near the C4a locus of the isoalloxazine moiety of
      the flavin, whereas dehydrogenases prefer another residue at this position.
      Mutation of the corresponding residue in GALDH (Ala-113 --> Gly) resulted in a
      striking 400-fold increase in oxygen reactivity, whereas the cytochrome c
      reductase activity is retained. The activity of the A113G variant shows a linear
      dependence on oxygen concentration (k(ox) = 3.5 x 10(5) m(-1) s(-1)), similar to
      most other flavoprotein oxidases. The Ala-113 --> Gly replacement does not change
      the reduction potential of the flavin but creates space for molecular oxygen to
      react with the reduced flavin. In the wild-type enzyme, Ala-113 acts as a
      gatekeeper, preventing oxygen from accessing the isoalloxazine nucleus. The
      presence of such an oxygen access gate seems to be a key factor for the
      prevention of oxidase activity within the VAO family and is absent in members
      that act as oxidases.

PMID- 19088071
TI  - Vesicular stomatitis virus matrix protein mutations that affect association with
      host membranes and viral nucleocapsids.
AB  - Viral matrix (M) proteins bind the nucleoprotein core (nucleocapsid) to host
      membranes during the process of virus assembly by budding. Previous studies using
      truncated M proteins had implicated the N-terminal 50 amino acids of the
      vesicular stomatitis virus M protein in binding both membranes and nucleocapsids
      and a sequence from amino acids 75-106 as an additional membrane binding region.
      Structure-based mutations were introduced into these two regions, and their
      effects on membrane association and incorporation into nucleocapsid-M protein
      complexes were determined using quantitative assays. The results confirmed that
      the N terminus of M protein is involved in association with plasma membranes as
      well as nucleocapsids, although these two activities were differentially affected
      by individual mutations. Mutations in the 75-106 region affected incorporation
      into nucleocapsid-M complexes but had only minor effects on association with
      membranes. The ability of site-specific mutant M proteins to complement growth of
      temperature-sensitive M mutant virus did not correlate well with the ability to
      associate with membranes or nucleocapsids, suggesting that complementation
      involves an additional activity of M protein. Mutants with similar abilities to
      associate with membranes and nucleocapsids but differing in complementation
      activity were incorporated into infectious cDNA clones. Infectious virus was
      repeatedly recovered containing mutant M proteins capable of complementation but
      was never recovered with mutant M proteins that lacked complementation activity,
      providing further evidence for a separate activity of M protein that is essential
      for virus replication.

PMID- 19088072
TI  - Copper transport activity of yeast Ctr1 is down-regulated via its C terminus in
      response to excess copper.
AB  - Copper is an essential yet toxic trace element. The Ctr1 family of proteins plays
      a critical role for copper uptake in eukaryotes. However, the mechanisms of
      action of Ctr1 are largely unknown. Our previous data demonstrated that copper
      transport induces conformational changes in the cytosolic C terminus of the yeast
      Saccharomyces cerevisiae Ctr1. To define the physiological significance of this
      molecular event and gain better insights into the mechanism of Ctr1-mediated
      copper uptake, we have characterized the functional roles of the Ctr1 C terminus.
      A Ctr1 mutant lacking the entire C-terminal cytosolic tail is functional in high
      affinity copper uptake; however, yeast cells expressing this mutant are extremely
      sensitive to excess copper. Toxic copper uptake is not attributed to elevated
      expression or distinct subcellular localization of this mutant as compared with
      wild type Ctr1. Further characterization of the function of Ctr1 containing
      deletions or site-directed mutations at the C terminus indicates a structural
      role for the C terminus in controlling Ctr1 activities. In response to excess
      copper, Ctr1-mediated copper transport is rapidly blocked in a C terminus
      dependent mechanism associated with direct binding of copper. We propose that
      conformational changes in the cytosolic tail of yeast Ctr1 by copper sensing
      within this domain lead to the inhibition of Ctr1-mediated copper transport.
      These data suggest a new regulatory mechanism by which yeast cells maintain
      homeostatic copper acquisition.

PMID- 19088073
TI  - STIM1- and Orai1-dependent store-operated calcium entry regulates human myoblast
      differentiation.
AB  - Our previous work on human myoblasts suggested that a hyperpolarization followed
      by a rise in [Ca(2+)](in) involving store-operated Ca(2+) entry (SOCE) channels
      induced myoblast differentiation. Advances in the understanding of the SOCE
      pathway led us to examine more precisely its role in post-natal human myoblast
      differentiation. We found that SOCE orchestrated by STIM1, the endoplasmic
      reticulum Ca(2+) sensor activating Orai Ca(2+) channels, is crucial. Silencing
      STIM1, Orai1, or Orai3 reduced SOCE amplitude and myoblast differentiation,
      whereas Orai2 knockdown had no effect. Conversely, overexpression of STIM1 with
      Orai1 increased SOCE and accelerated myoblast differentiation. STIM1 or Orai1
      silencing decreased resting [Ca(2+)](in) and intracellular Ca(2+) store content,
      but correction of these parameters did not rescue myoblast differentiation.
      Remarkably, SOCE amplitude correlated linearly with the expression of two early
      markers of myoblast differentiation, MEF2 and myogenin, regardless of the STIM or
      Orai isoform that was silenced. Unexpectedly, we found that the hyperpolarization
      also depends on SOCE, placing SOCE upstream of K(+) channel activation in the
      signaling cascade that controls myoblast differentiation. These findings indicate
      that STIM1 and Orai1 are key molecules for the induction of human myoblast
      differentiation.

PMID- 19088074
TI  - Role of flavinylation in a mild variant of multiple acyl-CoA dehydrogenation
      deficiency: a molecular rationale for the effects of riboflavin supplementation.
AB  - Mutations in the genes encoding the alpha-subunit and beta-subunit of the
      mitochondrial electron transfer flavoprotein (ETF) and the electron transfer
      flavoprotein:ubiquinone oxidoreductase (ETF:QO) cause multiple acyl-CoA
      dehydrogenation deficiency (MADD), a disorder of fatty acid and amino acid
      metabolism. Point mutations in ETF, which may compromise folding, and/or
      activity, are associated with both mild and severe forms of MADD. Here we report
      the investigation on the conformational and stability properties of the disease
      causing variant ETFbeta-D128N, and our findings on the effect of flavinylation in
      modulating protein conformational stability and activity. A combination of
      biochemical and biophysical methods including circular dichroism, visible
      absorption, flavin, and tryptophan fluorescence emission allowed the analysis of
      structural changes and of the FAD moiety. The ETFbeta-D128N variant retains the
      overall fold of the wild type, but under stress conditions its flavin becomes
      less tightly bound. Flavinylation is shown to improve the conformational
      stability and biological activity of a destabilized D128N variant protein.
      Moreover, the presence of flavin prevented proteolytic digestion by avoiding
      protein destabilization. A patient homozygous for the ETFbeta-D128N mutation
      developed severe disease symptoms in association with a viral infection and
      fever. In agreement, our results suggest that heat inactivation of the mutant may
      be more relevant at temperatures above 37 degrees C. To mimic a situation of
      fever in vitro, the flavinylation status was tested at 39 degrees C. FAD exerts
      the effect of a pharmacological chaperone, improving ETF conformation, and
      yielding a more stable and active enzyme. Our results provide a structural and
      functional framework that could help to elucidate the role that an increased
      cellular FAD content obtained from riboflavin supplementation may play in the
      molecular pathogenesis of not only MADD, but genetic disorders of flavoproteins
      in general.

PMID- 19088075
TI  - NS3 helicase from the hepatitis C virus can function as a monomer or oligomer
      depending on enzyme and substrate concentrations.
AB  - Hepatitis C virus NS3 helicase can unwind double-stranded DNA and RNA and has
      been proposed to form oligomeric structures. Here we examine the DNA unwinding
      activity of monomeric NS3. Oligomerization was measured by preparing a
      fluorescently labeled form of NS3, which was titrated with unlabeled NS3,
      resulting in a hyperbolic increase in fluorescence anisotropy and providing an
      apparent equilibrium dissociation constant of 236 nm. To evaluate the DNA binding
      activity of individual subunits within NS3 oligomers, two oligonucleotides were
      labeled with fluorescent donor or acceptor molecules and then titrated with NS3.
      Upon the addition of increasing concentrations of NS3, fluorescence energy
      transfer was observed, which reached a plateau at a 1:1 ratio of NS3 to
      oligonucleotides, indicating that each subunit within the oligomeric form of NS3
      binds to DNA. DNA unwinding was measured under multiple turnover conditions with
      increasing concentrations of NS3; however, no increase in specific activity was
      observed, even at enzyme concentrations greater than the apparent dissociation
      constant for oligomerization. An ATPase-deficient form of NS3, NS3(D290A), was
      prepared to explore the functional consequences of oligomerization. Under single
      turnover conditions in the presence of excess concentration of NS3 relative to
      DNA, NS3(D290A) exhibited a dominant negative effect. However, under multiple
      turnover conditions in which DNA concentration was in excess to enzyme
      concentration, NS3(D290A) did not exhibit a dominant negative effect. Taken
      together, these data support a model in which monomeric forms of NS3 are active.
      Oligomerization of NS3 occurs, but subunits can function independently or
      cooperatively, dependent upon the relative concentration of the DNA.

PMID- 19088076
TI  - SGK1 phosphorylation of IkappaB Kinase alpha and p300 Up-regulates NF-kappaB
      activity and increases N-Methyl-D-aspartate receptor NR2A and NR2B expression.
AB  - Serum- and glucocorticoid-inducible kinase 1 (SGK1) is a downstream target of
      phosphatidylinositol 3-kinase signaling, and it regulates various cellular and
      physiological functions, but the SGK1 substrate proteins and genes regulated by
      SGK1 are less known. Here we have identified IkappaB kinase alpha (IKKalpha) as a
      novel substrate of SGK1 by using biochemical and bioinformatic approaches. SGK1
      directly phosphorylates IKKalpha at Thr-23 and indirectly activates IKKalpha at
      Ser-180. Furthermore, SGK1 enhanced nuclear factor kappaB (NF-kappaB) activity
      and up-regulated N-methyl-d-aspartate receptor NR2A and NR2B expression through
      activation of IKKalpha at Thr-23 and Ser-180, and these two residues play an
      equally important role in mediating these effects of SGK1. Although SGK1 does not
      phosphorylate IKKbeta, IKKbeta activity is still required for IKK complex
      activation and for SGK1 phosphorylation and activation of NF-kappaB. In addition,
      SGK1 increased the acetylation of NF-kappaB through phosphorylation of p300 at
      Ser-1834, and this also leads to NF-kappaB activation and NR2A and NR2B
      expression. Moreover, an endogenous stimulus of SGK1, insulin, increased IKKalpha
      and NF-kappaB phosphorylation as well as NF-kappaB acetylation and NF-kappaB
      activity, but SGK1 small interfering RNA transfection blocked these effects of
      insulin. In examination of the functional significance of the SGK1-IKKalpha-NF
      kappaB signaling pathway, we found that transfection of the IKKalpha double
      mutant (IKKalphaT23A/S180A) to rat hippocampus antagonized SGK-1-mediated spatial
      memory facilitation. Our results together demonstrated novel substrate proteins
      of SGK1 and novel SGK1 signaling pathways. Activation of these signaling pathways
      enhances NR2A and NR2B expression that is implicated in neuronal plasticity.

PMID- 19088077
TI  - Primary murine airway smooth muscle cells exposed to poly(I,C) or tunicamycin
      synthesize a leukocyte-adhesive hyaluronan matrix.
AB  - Asthmatic attacks often follow viral infections with subsequent airway smooth
      muscle cell proliferation and the formation of an abnormal hyaluronan
      extracellular matrix with infiltrated leukocytes. In this study, we show that
      murine airway smooth muscle cells (MASM) treated with polyinosinic acid
      polycytidylic acid (poly(I,C)), a double-stranded RNA that simulates a viral
      infection, synthesize an abnormal hyaluronan matrix that binds leukocytes (U937
      cells). Synthesis of this matrix is initiated rapidly and accumulates linearly
      for approximately 10 h, reaching a plateau level approximately 7-fold higher than
      control cultures. MASM cells treated with tunicamycin, to induce endoplasmic
      reticulum stress, also rapidly initiate synthesis of the abnormal hyaluronan
      matrix with linear accumulation for approximately 10 h, but only reach a plateau
      level approximately 2-fold higher than control cultures. In contrast to
      poly(I,C), the response to tunicamycin depends on cell density, with pre
      confluent cells producing more abnormal matrix per cell. Furthermore, U937 cell
      adhesion per hyaluronan content is higher in the sparse matrix produced in
      response to tunicamycin, suggesting that the structure in the poly(I,C)-induced
      matrix masks potential binding sites. When MASM cells were exposed to tunicamycin
      and poly(I,C) at the same time, U937 cell adhesion was partially additive,
      implying that these two toxins stimulate hyaluronan synthesis through two
      different pathways. We also characterized the size of hyaluronan produced by MASM
      cells, in response to poly(I,C) and tunicamycin, and we found that it ranges from
      1500 to 4000 kDa, the majority of which was approximately 4000 kDa and not
      different in size than hyaluronan made by untreated cells.

PMID- 19088078
TI  - Activation of plant plasma membrane H+-ATPase by 14-3-3 proteins is negatively
      controlled by two phosphorylation sites within the H+-ATPase C-terminal region.
AB  - The proton pump ATPase (H(+)-ATPase) of the plant plasma membrane is regulated by
      an autoinhibitory C-terminal domain, which can be displaced by phosphorylation of
      the penultimate Thr residue and the subsequent binding of 14-3-3 proteins. We
      performed a mass spectrometric analysis of PMA2 (plasma membrane H(+)-ATPase
      isoform 2) isolated from Nicotiana tabacum suspension cells and identified two
      new phosphorylated residues in the enzyme 14-3-3 protein binding site: Thr(931)
      and Ser(938). When PMA2 was expressed in Saccharomyces cerevisiae, mutagenesis of
      each of these two residues into Asp prevented growth of a yeast strain devoid of
      its own H(+)-ATPases. When the Asp mutations were individually introduced in a
      constitutively activated mutant of PMA2 (E14D), they still allowed yeast growth
      but at a reduced rate. Purification of His-tagged PMA2 showed that the T931D or
      S938D mutation prevented 14-3-3 protein binding, although the penultimate
      Thr(955) was still phosphorylated, indicating that Thr(955) phosphorylation is
      not sufficient for full enzyme activation. Expression of PMA2 in an N. tabacum
      cell line also showed an absence of 14-3-3 protein binding resulting from the
      T931D or S938D mutation. Together, the data show that activation of H(+)-ATPase
      by the binding of 14-3-3 proteins is negatively controlled by phosphorylation of
      two residues in the H(+)-ATPase 14-3-3 protein binding site. The data also show
      that phosphorylation of the penultimate Thr and 14-3-3 binding each contribute in
      part to H(+)-ATPase activation.

PMID- 19088079
TI  - Induction of microRNA-221 by platelet-derived growth factor signaling is critical
      for modulation of vascular smooth muscle phenotype.
AB  - The platelet-derived growth factor (PDGF) signaling pathway is a critical
      regulator of animal development and homeostasis. Activation of the PDGF pathway
      leads to neointimal proliferative responses to artery injury; it promotes a
      switch of vascular smooth muscle cells (vSMC) to a less contractile phenotype by
      inhibiting the SMC-specific gene expression and increasing the rate of
      proliferation and migration. The molecular mechanism for these pleiotropic
      effects of PDGFs has not been fully described. Here, we identify the microRNA-221
      (miR-221), a small noncoding RNA, as a modulator of the phenotypic change of
      vSMCs in response to PDGF signaling. We demonstrate that miR-221 is
      transcriptionally induced upon PDGF treatment in primary vSMCs, leading to down
      regulation of the targets c-Kit and p27Kip1. Down-regulation of p27Kip1 by miR
      221 is critical for PDGF-mediated induction of cell proliferation. Additionally,
      decreased c-Kit causes inhibition of SMC-specific contractile gene transcription
      by reducing the expression of Myocardin (Myocd), a potent SMC-specific nuclear
      coactivator. Our study demonstrates that PDGF signaling, by modulating the
      expression of miR-221, regulates two critical determinants of the vSMC phenotype;
      they are SMC gene expression and cell proliferation.

PMID- 19088081
TI  - Vascular smooth muscle cells sense calcium: a new paradigm in vascular
      calcification.

PMID- 19088080
TI  - Silencing of the transforming growth factor-beta (TGFbeta) receptor II by Kruppel
      like factor 14 underscores the importance of a negative feedback mechanism in
      TGFbeta signaling.
AB  - The role of non-Smad proteins in the regulation of transforming growth factor
      beta (TGFbeta) signaling is an emerging line of active investigation. Here, we
      characterize the role of KLF14, as a TGFbeta-inducible, non-Smad protein that
      silences the TGFbeta receptor II (TGFbetaRII) promoter. Together with
      endocytosis, transcriptional silencing is a critical mechanism for down
      regulating TGFbeta receptors at the cell surface. However, the mechanisms
      underlying transcriptional repression of these receptors remain poorly
      understood. KLF14 has been chosen from a comprehensive screen of 24 members of
      the Sp/KLF family due to its TGFbeta inducibility, its ability to regulate the
      TGFbetaRII promoter, and the fact that this protein had yet to be functionally
      characterized. We find that KLF14 represses the TGFbetaRII, a function that is
      augmented by TGFbeta treatment. Mapping of the TGFbetaRII promoter, in
      combination with site-directed mutagenesis, electromobility shift, and chromatin
      immunoprecipitation assays, have identified distinct GC-rich sequences used by
      KLF14 to regulate this promoter. Mechanistically, KLF14 represses the TGFbetaRII
      promoter via a co-repressor complex containing mSin3A and HDAC2. Furthermore, the
      TGFbeta pathway activation leads to recruitment of a KLF14-mSin3A-HDAC2 repressor
      complex to the TGFbetaRII promoter, as well as the remodeling of chromatin to
      increase histone marks that associate with transcriptional silencing. Thus, these
      results describe a novel negative-feedback mechanism by which TGFbetaRII
      activation at the cell surface induces the expression of KLF14 to ultimately
      silence the TGFbetaRII and further expand the network of non-Smad transcription
      factors that participate in the TGFbeta pathway.

PMID- 19088082
TI  - Activation of neutral sphingomyelinase is involved in acute hypoxic pulmonary
      vasoconstriction.
AB  - AIMS: The mechanisms involved in hypoxic pulmonary vasoconstriction (HPV) are not
      yet fully defined. The aim of the study was to determine the role of protein
      kinase C zeta (PKCzeta) and neutral sphingomyelinase (nSMase) in HPV. METHODS AND
      RESULTS: Ceramide content was measured by immunocytochemistry and voltage-gated
      potassium channel (KV) currents were recorded by the patch clamp technique in
      isolated rat pulmonary artery smooth muscle cells (PASMC). Contractile responses
      were analysed in rat pulmonary arteries mounted in a wire myograph. Pulmonary
      pressure was recorded in anesthetized open-chest rats. Protein and mRNA
      expression were measured by western blot and RT-PCR, respectively. We found that
      hypoxia increased ceramide content in PASMC which was abrogated by inhibition of
      nSMase, but not acid sphingomyelinase (aSMase). The hypoxia-induced
      vasoconstrictor response in isolated pulmonary arteries and the inhibition of KV
      currents were strongly reduced by inhibition of PKCzeta or nSMase but not aSMase.
      The nSMase inhibitor GW4869 prevented HPV in vivo. The vasoconstrictor response
      to hypoxia was mimicked by exogenous addition of bacterial Smase and ceramide.
      nSMase2 mRNA expression was approximately 10-fold higher in pulmonary compared
      with mesenteric arteries. In mesenteric arteries, hypoxia failed to increase
      ceramide but exogenous SMase induced a contractile response. CONCLUSION: nSMase
      derived ceramide production and the activation of PKCzeta are early and necessary
      events in the signalling cascade of acute HPV.

PMID- 19088083
TI  - Effects of hypoxia-induced intrauterine growth restriction on cardiopulmonary
      structure and function during adulthood.
AB  - AIMS: Intrauterine growth restriction (IUGR), a condition affecting 7-15% of all
      pregnancies, is associated with an increased mortality rate during adulthood.
      Several animal models have been developed to study the effects of IUGR during
      adulthood. However, the in vivo characteristics of these models are still
      unknown. The main aim of this work was to evaluate, in vivo, the effects of IUGR
      on cardiopulmonary structure and function during adulthood. METHODS AND RESULTS:
      Pregnant Sprague Dawley rats were exposed to hypoxic (12% O2) or normoxic (21%
      O2) environments between day 15 and 21 of pregnancy. Offspring were raised to 4
      or 12 months old when a complete in vivo echocardiographic study was performed.
      In addition, ex vivo morphometry and isolated working heart experiments were
      performed. At birth, pups exposed to hypoxia had a smaller body weight and larger
      heart/body weight than controls. At 4 months of age, there were no significant
      differences between the groups. At 12 months of age, male but not female
      offspring exposed to prenatal hypoxia had smaller body weights and signs of left
      ventricular hypertrophy. In addition, both male and females animals exposed to
      prenatal hypoxia showed in vivo and ex vivo signs of left ventricular diastolic
      dysfunction and pulmonary hypertension by 12 months of age. CONCLUSION: Our study
      demonstrated that hypoxia-induced IUGR is associated with the development of
      chronic cardiopulmonary dysfunction during ageing. The implication of these
      findings is the potential usefulness of neonatal diagnosis as a predictor of
      cardiopulmonary outcomes during adulthood.

PMID- 19088084
TI  - Adaptive phenotypic plasticity of Pseudoroegneria spicata: response of stomatal
      density, leaf area and biomass to changes in water supply and increased
      temperature.
AB  - BACKGROUND AND AIMS: Changes in rainfall and temperature brought about through
      climate change may affect plant species distribution and community composition of
      grasslands. The primary objective of this study was to test how manipulation of
      water and temperature would influence the plasticity of stomatal density and leaf
      area of bluebunch wheatgrass, Pseudoroegneria spicata. It was hypothesized that:
      (1) an increased water supply will increase biomass and leaf area and decrease
      stomatal density, while a reduced water supply will cause the opposite effect;
      (2) an increase in temperature will reduce biomass and leaf area and increase
      stomatal density; and (3) the combinations of water and temperature treatments
      can be aligned along a stress gradient and that stomatal density will be highest
      at high stress. Methods The three water supply treatments were (1) ambient, (2)
      increased approx. 30% more than ambient through weekly watering and (3) decreased
      approx. 30 % less than ambient by rain shades. The two temperature treatments
      were (1) ambient and (2) increased approx. 1-3 degrees C by using open-top
      chambers. At the end of the second experimental growing season, above-ground
      biomass was harvested, oven-dried and weighed, tillers from bluebunch wheatgrass
      plants sampled, and the abaxial stomatal density and leaf area of tillers were
      measured. KEY RESULTS: The first hypothesis was partially supported--reducing
      water supply increased stomatal density, but increasing water supply reduced leaf
      area. The second hypothesis was rejected. Finally, the third hypothesis could not
      be fully supported--rather than a linear response there appears to be a parabolic
      stomatal density response to stress. CONCLUSIONS: Overall, the abaxial stomatal
      density and leaf area of bluebunch wheatgrass were plastic in their response to
      water and temperature manipulations. Although bluebunch wheatgrass has the
      potential to adapt to changing climate, the grass is limited in its ability to
      respond to a combination of reduced water and increased temperature.

PMID- 19088086
TI  - Gata2 is a tissue-specific post-mitotic selector gene for midbrain GABAergic
      neurons.
AB  - Midbrain GABAergic neurons control several aspects of behavior, but regulation of
      their development and diversity is poorly understood. Here, we further refine the
      midbrain regions active in GABAergic neurogenesis and show their correlation with
      the expression of the transcription factor Gata2. Using tissue-specific
      inactivation and ectopic expression, we show that Gata2 regulates GABAergic
      neuron development in the mouse midbrain, but not in rhombomere 1, where it is
      needed in the serotonergic lineage. Without Gata2, all the precursors in the
      embryonic midbrain fail to activate GABAergic neuron-specific gene expression and
      instead switch to a glutamatergic phenotype. Surprisingly, this fate switch is
      also observed throughout the neonatal midbrain, except for the GABAergic neurons
      located in the ventral dopaminergic nuclei, suggesting a distinct developmental
      pathway for these neurons. These studies identify Gata2 as an essential post
      mitotic selector gene of the GABAergic neurotransmitter identity and demonstrate
      developmental heterogeneity of GABAergic neurons in the midbrain.

PMID- 19088085
TI  - PP4 and PP2A regulate Hedgehog signaling by controlling Smo and Ci
      phosphorylation.
AB  - The seven-transmembrane protein Smoothened (Smo) and Zn-finger transcription
      factor Ci/Gli are crucial components in Hedgehog (Hh) signal transduction that
      mediates a variety of processes in animal development. In Drosophila, multiple
      kinases have been identified to regulate Hh signaling by phosphorylating Smo and
      Ci; however, the phosphatase(s) involved remain obscured. Using an in vivo RNAi
      screen, we identified PP4 and PP2A as phosphatases that influence Hh signaling by
      regulating Smo and Ci, respectively. RNAi knockdown of PP4, but not of PP2A,
      elevates Smo phosphorylation and accumulation, leading to increased Hh signaling
      activity. Deletion of a PP4-interaction domain (amino acids 626-678) in Smo
      promotes Smo phosphorylation and signaling activity. We further find that PP4
      regulates the Hh-induced Smo cell-surface accumulation. Mechanistically, we show
      that Hh downregulates Smo-PP4 interaction that is mediated by Cos2. We also
      provide evidence that PP2A is a Ci phosphatase. Inactivating PP2A regulatory
      subunit (Wdb) by RNAi or by loss-of-function mutation downregulates, whereas
      overexpressing regulatory subunit upregulates, the level and thus signaling
      activity of full-length Ci. Furthermore, we find that Wdb counteracts kinases to
      prevent Ci phosphorylation. Finally, we have obtained evidence that Wdb
      attenuates Ci processing probably by dephosphorylating Ci. Taken together, our
      results suggest that PP4 and PP2A are two phosphatases that act at different
      positions of the Hh signaling cascade.

PMID- 19088087
TI  - Ancestry-independent fate specification and plasticity in the developmental
      timing of a typical Drosophila neuronal lineage.
AB  - In the Drosophila CNS, combinatorial, interdependent, sequential genetic programs
      in neuroectodermal (NE) cells, prior to the formation of neuroblasts (NBs),
      determine the initial identity of NBs. Temporal factors are then sequentially
      expressed to change the temporal identity. It is unclear at what levels this
      positional and temporal information integrates to determine progeny cell
      identity. One idea is that this is a top-down linear process: the identity of a
      NB determines the identity of its daughter, the ganglion mother cell (GMC), the
      asymmetric division of the GMC and the fate specification of daughter cells of
      the GMC. Our results with midline (mid), which encodes a T-box protein, in a
      typical lineage, NB4-2-->GMC-1-->RP2/sib, suggest that at least part of the
      process operates in GMCs. That is, a GMC or a neuronal identity need not be
      determined at the NB or NE level. This is demonstrated by showing that Mid is
      expressed in a row 5 GMC (M-GMC), but not in its parent NB or NE cell. In mid
      mutants, M-GMC changes into GMC-1 and generates an RP2 and a sib without
      affecting the expression of key genes at the NE/NB levels. Expression of Mid in
      the M-GMC in mid mutants rescues the fate change, indicating that Mid specifies
      neurons at the GMC level. Moreover, we found a significant plasticity in the
      temporal window in which a neuronal lineage can develop. Although the extra GMC-1
      in mid mutants is born approximately 2 hours later than the bona fide GMC-1, it
      follows the same developmental pattern as the bona fide GMC-1. Thus, a GMC
      identity can be independent of parental identity and GMC formation and
      elaboration need not be strictly time-bound.

PMID- 19088088
TI  - The bHLH transcription factor Olig3 marks the dorsal neuroepithelium of the
      hindbrain and is essential for the development of brainstem nuclei.
AB  - The Olig3 gene encodes a bHLH factor that is expressed in the ventricular zone of
      the dorsal alar plate of the hindbrain. We found that the Olig3(+) progenitor
      domain encompassed subdomains that co-expressed Math1, Ngn1, Mash1 and Ptf1a.
      Olig3(+) cells give rise to neuronal types in the dorsal alar plate that we
      denote as class A neurons. We used genetic lineage tracing to demonstrate that
      class A neurons contribute to the nucleus of the solitary tract and to
      precerebellar nuclei. The fate of class A neurons was not correctly determined in
      Olig3 mutant mice. As a consequence, the nucleus of the solitary tract did not
      form, and precerebellar nuclei, such as the inferior olivary nucleus, were absent
      or small. At the expense of class A neurons, ectopic Lbx1(+) neurons appeared in
      the alar plate in Olig3 mutant mice. By contrast, electroporation of an Olig3
      expression vector in the chick hindbrain suppressed the emergence of Lbx1(+)
      neurons. Climbing fiber neurons of the inferior olivary nucleus express Foxd3 and
      require Olig3 as well as Ptf1a for the determination of their fate. We observed
      that electroporation of Olig3 and Ptf1a expression vectors, but not either alone,
      induced Foxd3. We therefore propose that Olig3 can cooperate with Ptf1a to
      determine the fate of climbing fiber neurons of the inferior olivary nucleus.

PMID- 19088089
TI  - Gene regulatory networks underlying the compartmentalization of the Ciona central
      nervous system.
AB  - The tripartite organization of the central nervous system (CNS) may be an ancient
      character of the bilaterians. However, the elaboration of the more complex
      vertebrate brain depends on the midbrain-hindbrain boundary (MHB) organizer,
      which is absent in invertebrates such as Drosophila. The Fgf8 signaling molecule
      expressed in the MHB organizer plays a key role in delineating separate
      mesencephalon and metencephalon compartments in the vertebrate CNS. Here, we
      present evidence that an Fgf8 ortholog establishes sequential patterns of
      regulatory gene expression in the developing posterior sensory vesicle, and the
      interleaved ;neck' region located between the sensory vesicle and visceral
      ganglion of the simple chordate Ciona intestinalis. The detailed characterization
      of gene networks in the developing CNS led to new insights into the mechanisms by
      which Fgf8/17/18 patterns the chordate brain. The precise positioning of this Fgf
      signaling activity depends on an unusual AND/OR network motif that regulates
      Snail, which encodes a threshold repressor of Fgf8 expression. Nodal is
      sufficient to activate low levels of the Snail repressor within the neural plate,
      while the combination of Nodal and Neurogenin produces high levels of Snail in
      neighboring domains of the CNS. The loss of Fgf8 patterning activity results in
      the transformation of hindbrain structures into an expanded mesencephalon in both
      ascidians and vertebrates, suggesting that the primitive MHB-like activity
      predates the vertebrate CNS.

PMID- 19088090
TI  - Homeodomain-interacting protein kinases (Hipks) promote Wnt/Wg signaling through
      stabilization of beta-catenin/Arm and stimulation of target gene expression.
AB  - The Wnt/Wingless (Wg) pathway represents a conserved signaling cascade involved
      in diverse biological processes. Misregulation of Wnt/Wg signal transduction has
      profound effects on development. Homeodomain-interacting protein kinases (Hipks)
      represent a novel family of serine/threonine kinases. Members of this group (in
      particular Hipk2) are implicated as important factors in transcriptional
      regulation to control cell growth, apoptosis and development. Here, we provide
      genetic and phenotypic evidence that the sole Drosophila member of this family,
      Hipk, functions as a positive regulator in the Wg pathway. Expression of hipk in
      the wing rescues loss of the Wg signal, whereas loss of hipk can enhance
      decreased wg signaling phenotypes. Furthermore, loss of hipk leads to diminished
      Arm protein levels, whereas overexpression of hipk promotes the Wg signal by
      stabilizing Arm, resulting in activation of Wg responsive targets. In Wg
      transcriptional assays, Hipk enhanced Tcf/Arm-mediated gene expression in a
      kinase-dependent manner. In addition, Hipk can bind to Arm and Drosophila Tcf,
      and phosphorylate Arm. Using both in vitro and in vivo assays, Hipk was found to
      promote the stabilization of Arm. We observe similar molecular interactions
      between Lef1/beta-catenin and vertebrate Hipk2, suggesting a direct and conserved
      role for Hipk proteins in promoting Wnt signaling.

PMID- 19088091
TI  - The Drosophila homolog of vertebrate Islet1 is a key component in early
      cardiogenesis.
AB  - In mouse, the LIM-homeodomain transcription factor Islet1 (Isl1) has been shown
      to demarcate a separate cardiac cell population that is essential for the
      formation of the right ventricle and the outflow tract of the heart. Whether Isl1
      plays a crucial role in the early regulatory network of transcription factors
      that establishes a cardiac fate in mesodermal cells has not been fully resolved.
      We have analyzed the role of the Drosophila homolog of Isl1, tailup (tup), in
      cardiac specification and formation of the dorsal vessel. The early expression of
      Tup in the cardiac mesoderm suggests that Tup functions in cardiac specification.
      Indeed, tup mutants are characterized by a reduction of the essential early
      cardiac transcription factors Tin, Pnr and Dorsocross1-3 (Doc). Conversely, Tup
      expression depends on each of these cardiac factors, as well as on the early
      inductive signals Dpp and Wg. Genetic interactions show that tup cooperates with
      tin, pnr and Doc in heart cell specification. Germ layer-specific loss-of
      function and rescue experiments reveal that Tup also functions in the ectoderm to
      regulate cardiogenesis and implicate the involvement of different LIM-domain
      interacting proteins in the mesoderm and ectoderm. Gain-of-function analyses for
      tup and pnr suggest that a proper balance of these factors is also required for
      the specification of Eve-expressing pericardial cells. Since tup is required for
      proper cardiogenesis in an invertebrate organism, we believe it is appropriate to
      include tup/Isl1 in the core set of ancestral cardiac transcription factors that
      govern a cardiac fate.

PMID- 19088093
TI  - Best interests, patient participation and the Mental Capacity Act 2005.

PMID- 19088092
TI  - The Bax/Bak ortholog in Drosophila, Debcl, exerts limited control over programmed
      cell death.
AB  - Bcl-2 family members are pivotal regulators of programmed cell death (PCD). In
      mammals, pro-apoptotic Bcl-2 family members initiate early apoptotic signals by
      causing the release of cytochrome c from the mitochondria, a step necessary for
      the initiation of the caspase cascade. Worms and flies do not show a requirement
      for cytochrome c during apoptosis, but both model systems express pro- and anti
      apoptotic Bcl-2 family members. Drosophila encodes two Bcl-2 family members,
      Debcl (pro-apoptotic) and Buffy (anti-apoptotic). To understand the role of Debcl
      in Drosophila apoptosis, we produced authentic null alleles at this locus.
      Although gross development and lifespans were unaffected, we found that Debcl was
      required for pruning cells in the developing central nervous system. debcl
      genetically interacted with the ced-4/Apaf1 counterpart dark, but was not
      required for killing by RHG (Reaper, Hid, Grim) proteins. We found that debcl(KO)
      mutants were unaffected for mitochondrial density or volume but, surprisingly, in
      a model of caspase-independent cell death, heterologous killing by murine Bax
      required debcl to exert its pro-apoptotic activity. Therefore, although debcl
      functions as a limited effector of PCD during normal Drosophila development, it
      can be effectively recruited for killing by mammalian members of the Bcl-2 gene
      family.

PMID- 19088094
TI  - Redo medical thoracoscopy is feasible in patients with pleural diseases - a
      series.
AB  - Previous pleural endoscopy is considered to be a relative contraindication to
      further medical thoracoscopy. We reviewed our experience in patients undergoing
      more than one thoracoscopy irrespective of the primary indication. From January
      2001 to December 2006, patient baseline characteristics, endoscopic appearance
      and technique, volume of pleural fluid and final histological diagnosis were
      collated in all patients undergoing more than one thoracoscopy. The endpoints
      were morbidity and mortality related to the procedures, to compare the length of
      procedure time between pleural endoscopies in individual patients and the degree
      of difficulty of the second or subsequent thoracoscopic procedure. During this
      period, 29 patients underwent 'redo' thoracoscopy resulting in a total of 61
      procedures (rate of 'redo' thoracoscopy; 9.1%). The mean time between
      thoracoscopies was 5.3+/-3.8 months. Although pleural adhesions were more common
      at the time of the subsequent procedure, it did not result in failure to induce a
      pneumothorax or perform the procedure. There was no difference in the duration of
      procedure between the primary and subsequent thoracoscopy (P=0.46), as well as no
      complications directly attributed to the repeat pleural endoscopy. Repeat medical
      thoracoscopy is technically feasible in patients with pleural disease without an
      associated increased morbidity and mortality.

PMID- 19088095
TI  - Unusually giant splenic artery and vein aneurysm with arteriovenous fistula with
      hypersplenism in a nulliparous woman.
AB  - Although splenic artery aneurysm (SAA) is the commonest visceral and third most
      common intra abdominal aneurysm after aorta and iliac artery, aneurysm of splenic
      artery along with aneurysm of splenic vein with arteriovenous (a-v) fistula
      communication between them is a rare entity. Most are <3 cm in diameter. Giant
      true SAAs are rare and very few lesions >10 cm have been reported. We hereby
      report a case of an 18 cm x 15 cm size splenic artery and vein aneurysm with a-v
      fistula in an adult female nulliparous woman who presented with progressively
      enlarging pulsatile mass in the left upper abdomen with long-standing intractable
      pancytopenia and splenomegaly. Diagnosis was established by CT (computed
      tomogram) angiogram and laboratory tests. Laparotomy demonstrated huge well
      defined aneurysm of splenic artery and vein with splenic a-v fistula, extending
      in all except the right lower and inferior quadrants of the abdomen along with
      splenomegaly. Aneurysmectomy with splenectomy was done.

PMID- 19088096
TI  - Surgical treatment of catamenial pneumothorax: a single centre experience.
AB  - We retrospectively reviewed our experience with catamenial pneumothorax (CP) in
      terms of treatment and follow-up. From 1993 to 2008, ten women presented at our
      department with CP. CP was right-sided in all patients: seven presented
      diaphragmatic defects including one endometriosis, five had apical bulla or blebs
      that in three patients were the only pathological findings. Surgical approach was
      thoracoscopic with a muscle-sparing thoracotomy when diaphragmatic defects where
      present. All patients underwent apical resection and apical pleurectomy
      associated in seven cases with diaphragmatic plication and chemical pleurodesis.
      After surgery nine patients underwent hormonal treatment: three were put on
      estrogen-progesterone complex treatment and six received gonadotropin-releasing
      hormone agonist (GnRH agonist). Recurrence rate was 40% and it was significantly
      correlated with estrogen-progesterone treatment (P<0.005). The mean follow-up was
      52+/-32 months (range 14-168). At the present time, no recurrence has occurred in
      all women. Occurrence of CP is often underestimated. At the time of surgery the
      diaphragm should be carefully inspected for defects and/or endometriosis.
      Standard pleurodesis may not suffice and we suggest apical resection and apical
      pleurectomy associated with a diaphragmatic procedure when indicated. Hormonal
      treatment with GnRH agonist seems to improve the outcome.

PMID- 19088097
TI  - Anticardiolipin antibodies in patients with venous thromboembolic disease from a
      Spanish rural area.

PMID- 19088098
TI  - Use of aspirin versus clopidogrel plus aspirin after coronary artery bypass graft
      surgery.
AB  - Aspirin and clopidogrel together reduce the risk of recurrent thrombosis-related
      events in patients with acute coronary syndromes or stent revascularization and
      may reduce thrombosis-induced saphenous vein graft failure. In this
      retrospective, observational study, 4297 patients were assigned to 2 groups after
      coronary artery bypass graft surgery, based on medications prescribed at hospital
      discharge: aspirin only (n = 3318) or aspirin plus clopidogrel (n = 979). At 4
      year follow-up, unadjusted survival was similar between the 2 groups (aspirin
      clopidogrel, 87.9% vs aspirin-only, 88.8%, P = .43). After statistical adjustment
      using Cox regression analysis, dual anti-platelet therapy at hospital discharge
      was not associated with improved survival (odds ratio 1.055, 95% confidence
      interval 0.7-1.4, P = .72). In propensity score-based, case-matched populations
      (962 patients each), similar results were obtained (odds ratio 0.996, 95%
      confidence interval 0.7-1.4, P = .98). In our study population, aspirin plus
      clopidogrel did not provide survival benefit over treatment with aspirin alone in
      4 years after coronary artery bypass graft surgery.

PMID- 19088099
TI  - Smoking, abdominal aortic aneurysms, and ischemic heart disease: is there a link?

PMID- 19088100
TI  - The effect of regulation on pharmaceutical revenues: experience in nineteen
      countries.
AB  - We describe pharmaceutical regulations in nineteen developed countries from 1992
      to 2004 and analyze how different regulations affect pharmaceutical revenues.
      First, there has been a trend toward increased regulation. Second, most
      regulations reduce pharmaceutical revenues significantly. Third, since 1994, most
      countries adopting new regulations already had some regulation in place. We find
      that incremental regulation of this kind had a smaller impact on costs. However,
      introducing new regulations in a largely unregulated market, such as the United
      States, could greatly reduce pharmaceutical revenues. Finally, we show that the
      cost-reducing effects of price controls increase the longer they remain in place.

PMID- 19088101
TI  - U.S. pharmaceutical policy in a global marketplace.
AB  - U.S. consumers generate more pharmaceutical revenue per person than Europeans do.
      This has led some U.S. policymakers to call for limits on U.S. pharmaceutical
      spending and prices. Using a microsimulation approach, we analyze the welfare
      impacts of lowering U.S. prices toward European levels, and how these impacts
      vary with key modeling assumptions. Under the assumptions most favorable to them,
      price controls generate modest benefits (a few thousand dollars per person).
      However, for the remainder of plausible assumptions, price controls generate
      costs that are an order of magnitude higher. In contrast, publicly financing
      reductions in consumer prices, without affecting manufacturer prices, delivers
      benefits in virtually all plausible cases.

PMID- 19088102
TI  - Prescription drug spending trends in the United States: looking beyond the
      turning point.
AB  - Annual growth in real prescription drug spending averaged 9.9 percent during 1997
      2007 but has slowed since 2003, falling to 1.6 percent in 2007. More patent
      expirations, increased generic penetration, and reduced new product innovations
      have contributed to this turning point. We document trends and identify
      underlying components: declines in the role of blockbuster drugs, increased
      importance of biologics and vaccines relative to traditional pharmaceuticals, and
      a changing medication mix away from those prescribed principally by primary care
      physicians toward those mostly prescribed by specialists. We conclude with policy
      implications.

PMID- 19088103
TI  - Price controls and global pharmaceutical progress.
AB  - This Perspective reviews critically the work on price control impacts by Darius
      Lakdawalla and colleagues. It argues that the innovation elasticity of 3.0
      emphasized by the authors is too high, exaggerating the long-run costs of price
      controls. It argues, too, that the drugs chosen for the authors' analysis are
      neither the most therapeutically innovative candidates nor those whose
      development is most likely to be discouraged by price controls.

PMID- 19088104
TI  - Two ideas to increase innovation and reduce pharmaceutical costs and prices.
AB  - The pharmaceutical industry is undergoing a period of uncertainty. Profits are
      being squeezed by increasing costs and competitive pressures, and new drug
      production is slowing down. This Perspective reviews two policies that could
      assist in realigning incentives toward genuine innovation while also keeping drug
      spending growth under check. Value-based pricing can incentivize genuinely new
      discoveries and align research and development with social welfare. Public
      funding of clinical trials likewise can reduce both pharmaceutical costs and
      prices and direct research effort in a manner that is more socially productive
      than the current state of affairs.

PMID- 19088105
TI  - A study on the impact of operator experience on the patient radiation exposure in
      coronary angiography examinations.
AB  - The aim of the current study was to investigate the effect of cardiologists'
      experience on the patient received dose during coronary angiography. The exposure
      parameters including fluoroscopy time, total kerma-area product (KAP), total air
      kerma, fluoroscopy and cine acquisition KAP and air-kerma for five senior
      cardiologists with the experience of 6-10 y were recorded. The range of values
      for fluoroscopy time and total KAP were 2.17- 4.19 min and 12.06-21.06 Gy cm(2),
      respectively, in our diagnostic coronary examinations, which was below the
      recommended reference values. The differences among cardiologists were analysed
      statistically using one-way ANOVA test. The fluoroscopy KAP and air-kerma results
      showed statistically significant differences between cardiologists. However, the
      experience of the cardiologists showed no relation with patient received dose.
      According to the results, training in radiation protection as a requisite for
      interventional cardiologists was recommended.

PMID- 19088106
TI  - Anti-angiogenic effects of green tea catechin on an experimental endometriosis
      mouse model.
AB  - BACKGROUND: The development of new blood vessels plays an essential role in
      growth and survival of endometriosis. Epigallocatechin gallate (EGCG) from green
      tea has powerful anti-angiogenic properties and our aim was to evaluate these
      properties in experimental endometriosis. METHODS AND RESULTS: Eutopic
      endometrium from endometriosis patients was transplanted s.c. to severely
      compromised immunodeficient mice, randomly treated i.p. with EGCG (anti
      angiogenic and -oxidant), Vitamin E (a non-angiogenic antioxidant) or saline for
      2 weeks. The endometrial implant, including adjacent host outer skin and
      subcutaneous layers plus inner abdominal muscle and peritoneum, was collected.
      New microvessels were determined by species-specific immunohistochemistry.
      Angiogenic factors in lesions and abdominal muscle were detected by quantitative
      real-time PCR. Apoptosis was studied by terminal deoxynucleotidyltransferase
      mediated dUTP nick-end labelling and quantitative real-time PCR. In saline
      control, endometrial implants developed new blood vessels with proliferating
      glandular epithelium and were tightly adhered to host subcutaneous and abdominal
      muscle layers. After EGCG, endometriotic lesions were smaller than control (P <
      0.05), and glandular epithelium was smaller and eccentrically distributed.
      Angiogenesis in lesions from the implant and adjacent tissues was under
      developed, and microvessel size and density were lower (both P < 0.01) than
      control. mRNA for angiogenic vascular endothelial growth factor A, but not
      hypoxia inducible factor 1, alpha subunit, was significantly down-regulated in
      lesions after EGCG (P < 0.05). In addition, apoptosis in the lesions was more
      obvious, and nuclear factor kappa B and mitogen activated protein kinase 1 mRNA
      levels were up-regulated (P < 0.05) after EGCG treatment. No differences were
      observed with Vitamin E treatment. CONCLUSIONS: EGCG significantly inhibits the
      development of experimental endometriosis through anti-angiogenic effects.

PMID- 19088107
TI  - Induction of ovulation by a potent, orally active, low molecular weight agonist
      (Org 43553) of the luteinizing hormone receptor.
AB  - BACKGROUND: In assisted reproductive technology, human chorionic gonadotrophin
      (hCG) is administered subcutaneously for the induction of oocyte maturation and
      ovulation. Our efforts to develop orally bioavailable luteinizing hormone (LH)
      receptor agonists have led to the discovery of Org 43553, a low molecular weight
      (LMW) LH receptor (LH-R) agonist. METHODS: Org 43553 was tested in vitro and in
      vivo in pre-clinical pharmacological models to demonstrate efficacy and oral
      availability. RESULTS: Org 43553 is a potent stimulator of the human LH-R in
      vitro (EC(50) 3.7 nM). In primary mouse Leydig cells, Org 43553 stimulated
      testosterone production. Pharmacokinetic analyses showed high oral
      bioavailability in rats (79%) and dogs (44%) with a shorter half-life compared
      with hCG (3.4 versus 5.6 h in the rat). Ovulation induction by Org 43553 was
      demonstrated in immature mice as well as in cyclic rats after single-dose oral
      administration (50 mg/kg). The ovulated oocytes were of good quality as
      demonstrated by successful fertilization and implantation of normal embryos. In
      male rats, testosterone production was substantially induced after oral
      administration. CONCLUSIONS: Org 43553 is the first LMW LH-R mimetic with
      demonstrated in vivo efficacy upon oral administration and could therefore
      replace subcutaneously administered hCG. The elimination half-life of Org 43553
      is substantially shorter than hCG, which could potentially represent a clinical
      benefit in reducing the risk of ovarian hyperstimulation syndrome (OHSS).

PMID- 19088108
TI  - Influence of menstrual cycle on circulating endothelial progenitor cells.
AB  - BACKGROUND: Endothelial progenitor cells (EPCs) are circulating mononuclear cells
      that participate in angiogenesis. The aim of this study was to determine the
      influence of the menstrual cycle on the number and function of EPCs, and to
      investigate their relationship with circulating concentrations of sex steroids
      and inflammatory mediators. METHODS: Ten healthy nulliparous, premenopausal, non
      smoking women with regular menses were studied over a single menstrual cycle.
      Venepuncture was performed in the menstrual, follicular, peri-ovulatory and
      luteal phases. EPCs were quantified by flow cytometry (CD133(+)CD34(+)KDR(+)
      phenotype) and the colony-forming unit (CFU-EPC) functional assay. Circulating
      concentrations of estradiol, progesterone and inflammatory mediators (TNF-alpha,
      IL-6, sICAM-1 and VEGF) were measured by immunoassays. RESULTS: The numbers of
      CD133(+)CD34(+)KDR(+) cells were higher in the follicular phase (0.99 +/- 0.3 x
      10(6) cells/l) compared with the peri-ovulatory phase (0.29 +/- 0.1 x 10(6)
      cells/l; P < 0.05). In contrast, the numbers of CFU-EPCs did not vary over the
      menstrual cycle. There were no correlations between EPCs and concentrations of
      either circulating sex steroids or inflammatory mediators. CONCLUSIONS:
      CD133(+)CD34(+)KDR(+) cells but not CFU-EPCs vary during the menstrual cycle. Our
      findings suggest a potential role for circulating EPCs in the normal cycle of
      physiological angiogenesis and repair of the uterine endometrium that is
      independent of circulating sex steroids or inflammatory mediators.

PMID- 19088109
TI  - Sustained replication in endometrium of women with endometriosis occurs without
      evoking a DNA damage response.
AB  - BACKGROUND: To test our hypothesis that eutopic secretory phase endometrium from
      women with endometriosis is similar to proliferative phase endometrium from
      fertile women without endometriosis, we explored the expression of regulators of
      cell fate across the menstrual cycle. METHODS: Endometrial biopsies were taken
      from 73 women, comprising 38 women with surgically diagnosed active peritoneal
      endometriosis (Group 1) and 35 fertile women without endometriosis (Group 2).
      Nucleolin, proliferating cell nuclear antigen (PCNA), telomerase and histone
      gamma-H2AX expression was evaluated by immunohistochemistry and mean telomere
      length (TL) by quantitative PCR. RESULTS: We have immunolocalized nucleolin and
      gamma-H2AX in the benign premenopausal endometrium for the first time. All
      markers were present in the proliferative phase endometrium of all women. In
      Group 2, during the secretory phase, proliferative markers declined with a
      paradoxical increase in stromal gamma-H2AX. Women in Group 1, however, showed a
      persistent immunoreactivity for the proliferative markers, while the staining for
      gamma-H2AX decreased in secretory endometrium (P < 0.05). This difference between
      groups was significant in both stroma and glands for nucleolin (P < 0.0001), PCNA
      (P < 0.01) and gamma-H2AX (P < 0.05) in the secretory phase. We showed a positive
      correlation between mean TL and nucleolin expression (glandular r = 0.37, P =
      0.002; stromal r = 0.4, P = 0.001), telomerase immunoreactivity (glandular r =
      0.33, P = 0.009; stromal r = 0.4, P = 0.001) and glandular PCNA (r = 0.35, P =
      0.004), whereas a negative correlation was seen between mean TL and gamma-H2AX (r
      = -0.28, P = 0.04). CONCLUSIONS: These findings demonstrate that the state of
      replication seen in secretory phase endometrium from women with active peritoneal
      endometriosis is not a simple extension of the proliferative phase.

PMID- 19088110
TI  - Localization of matrix metalloproteinase (MMP)-2, MMP-9 and tissue inhibitors for
      MMPs (TIMPs) in uterine natural killer cells in early human pregnancy.
AB  - BACKGROUND: Invasion by extravillous trophoblast into uterine decidua and
      myometrium with remodeling of spiral arteries is essential for normal human
      pregnancy and is tightly regulated. Uterine natural killer (uNK) cells appear to
      be a major maternal regulator of placentation through the secretion of growth
      factors, cytokines and proteinases. METHOD: Matrix metalloproteinase (MMP)-2 and
      MMP-9 activity in placental bed biopsies was studied using in situ gelatin
      zymography. Expression by uNK cells of MMP-2, MMP-9 and their tissue inhibitors,
      TIMP-1, TIMP-2 and TIMP-3, was localized in the placental bed by
      immunohistochemistry. Levels of MMP-2, MMP-9, TIMP-1, TIMP-2 and TIMP-3 secreted
      into 24 h cell culture supernatants of isolated uNK and unseparated (total)
      decidual cells (8-10 and 12-14 weeks gestation, n = 10 each group) were
      determined by gelatin gel zymography or western blot as appropriate. RESULTS:
      Gelatinase activity in situ appeared greater in decidua than myometrium. uNK
      cells showed strong immunostaining for MMP-2 and TIMP-2. MMP-9 activity was lower
      in uNK cells than total decidual supernatants (8-10 weeks: P = 0.0003; 12-14
      weeks: P = 0.0012). In contrast, there was no difference in MMP-2 secreted by
      either uNK cell or total decidual cultures. CONCLUSIONS: uNK cells from early
      human pregnancy decidua possess innate protease activity, especially MMP-2,
      providing further evidence for a role for these cells in regulation of
      trophoblast invasion and spiral artery remodeling in early placentation.

PMID- 19088111
TI  - In vitro testing of rationally designed spermicides for selectively targeting
      human sperm in vagina to ensure safe contraception.
AB  - BACKGROUND: Rational synthesis of novel structures resulted in two unique
      molecules (DSE-36 and DSE-37, disulphide esters of carbothioic acid) that killed
      sperm 25 times more strongly and with a precisely targeted action than nonoxynol
      9 (N-9). We examine the effects of DSE-36 and DSE-37 on human spermatozoa versus
      HeLa cells to establish specificity and safety compared with N-9. METHODS AND
      RESULTS: At spermicidal EC(100) (20 microg/ml) DSE-36 and DSE-37 killed 100%
      sperm in <30 s (Sander-Cramer assay) and at EC(50) induced apoptosis in sperm
      (Annexin-V-fluorescein isothiocyanate and JC-1 labelling and Flow Cytometry) in 3
      h. However, at EC(100) these molecules had no effect on HeLa cells by 24 h or on
      cell viability [3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyl tetrazolium bromide
      (MTT) assay], surface ultrastructure (scanning electron microscopy), Annexin-V
      and JC-1 labelling pattern and reactive oxygen species (ROS) generation. N-9,
      with a spermicidal EC(100) of 500 microg/ml, decreased HeLa cell viability at 20
      microg/ml in 24 h (P < 0.001), accompanied by acute damage to cell surface
      ultrastructural topography, induction of apoptosis and ROS generation. Unlike DSE
      36 and DSE-37, N-9 also significantly induced mRNA levels (RT-PCR) of pro
      inflammatory biomarkers (interleukin (IL)-1 alpha, IL-6, IL-8, RANTES) in HeLa
      cells and increased IL-6 and IL-8 secretion (P < 0.001, enzyme-linked
      immunosorbent assay). Furthermore, DSE-36 and DSE-37 did not inhibit
      Lactobacillus growth at EC(100) and exhibited mild microbicidal activity against
      Trichomonas vaginalis, while N-9 inhibited Lactobacillus and Trichomonas growth
      but had a lower prophylactic index. CONCLUSIONS: The ability of these novel
      spermicides to kill sperm almost instantaneously at innocuously low concentration
      indicates their worth as improved active ingredients for vaginal contraceptive
      preparations compared with N-9.

PMID- 19088112
TI  - Sex-specific differences in fetal germ cell apoptosis induced by ionizing
      radiation.
AB  - BACKGROUND: We have previously shown that male human fetal germ cells are highly
      radiosensitive and that their death depends on p53 activation. Male germ cell
      apoptosis was initiated with doses as low as 0.1 Gy and was prevented by
      pifithrin alpha, a p53 inhibitor. In this study, we investigated the
      radiosensitivity of early female and male fetal proliferating germ cells. METHODS
      AND RESULTS: Both male and female fetal germ cells displayed a similar number of
      gamma H2AX foci in response to ionizing radiation (IR). In organ culture of human
      fetal ovaries, the germ cells underwent apoptosis only when exposed to high doses
      of IR (1.5 Gy and above). Accumulation of p53 was detected in irradiated male
      human fetal germ cells but not in female ones. Inhibition of p53 with pifithrin
      alpha did not affect oogonia apoptosis following irradiation. IR induced
      apoptosis similarly in mouse fetal ovaries in organ culture and in vivo during
      oogonial proliferation. Germ cell survival in testes from p53 knockout or p63
      knockout mice exposed to IR was better than wild-type, whereas female germ cell
      survival was unaffected by p53 or p63 knockout. CONCLUSIONS: These findings show
      that pre-meiotic male and female fetal germ cells behave differently in response
      to a genotoxic stress--irradiation--with oogonia being less sensitive and
      undergoing p53-independent apoptosis.

PMID- 19088113
TI  - Directed evolution of estrogen receptor proteins with altered ligand-binding
      specificities.
AB  - Transcriptional activators that respond to ligands with no cellular targets are
      powerful tools that can confer regulated expression of a transgene in almost all
      biological systems. In this study, we altered the ligand-binding specificity of
      the human estrogen receptor alpha (hER alpha) so that it would recognize a non
      steroidal synthetic compound with structural similarities to the phytoestrogen
      resveratrol. For this purpose, we performed iterative rounds of site-specific
      saturation mutagenesis of a fixed set of ligand-contacting residues and
      subsequent random mutagenesis of the entire ligand-binding domain. Selection of
      the receptor mutants and quantification of the interaction were carried out by
      exploiting a yeast two-hybrid system that reports the ligand-dependent
      interaction between hER alpha and steroid receptor coactivator-1 (SRC-1). The
      screen was performed with a synthetic ligand (CV3320) that promoted growth of the
      reporter yeast strain to half maximal levels at a concentration of 3.7 microM.
      The optimized receptor mutant (L384F/L387M/Y537S) showed a 67-fold increased
      activity to the synthetic ligand CV3320 (half maximal yeast growth at 0.055
      microM) and a 10-fold decreased activity to 17beta-estradiol (E2; half maximal
      yeast growth at 4 nM). The novel receptor-ligand pair partially fulfills the
      requirements for a specific 'gene switch' as it responds to concentrations of the
      synthetic ligand which do not activate the wildtype receptor. Due to its residual
      responsiveness to E2 at concentrations (4 nM) that might occur in vivo, further
      improvements have to be performed to render the system applicable in organisms
      with endogenous E2 synthesis.

PMID- 19088114
TI  - A 3G approach to a 3-dimensional problem.

PMID- 19088116
TI  - JECH: new editorial directions.

PMID- 19088115
TI  - Social inequalities in mortality by cause among men and women in France.
AB  - BACKGROUND: The aim of this study was to compare inequalities in mortality (all
      causes and by cause) by occupational group and educational level between men and
      women living in France in the 1990s. METHODS: Data were analysed from a permanent
      demographic sample currently including about one million people. The French
      Institute of Statistics (INSEE) follows the subjects and collects demographic,
      social and occupational information from the census schedules and vital status
      forms. Causes of death were obtained from the national file of the French
      Institute of Health and Medical Research (INSERM). A relative index of inequality
      (RII) was calculated to quantify inequalities as a function of educational level
      and occupational group. Overall all-cause mortality, mortality due to cancer,
      mortality due to cardiovascular disease and mortality due to external causes
      (accident, suicide, violence) were considered. RESULTS: Overall, social
      inequalities were found to be wider among men than among women, for all-cause
      mortality, cancer mortality and external-cause mortality. However, this trend was
      not observed for cardiovascular mortality, for which the social inequalities were
      greater for women than for men, particularly for mortality due to ischaemic
      cardiac diseases. CONCLUSIONS: This study provides evidence for persistent social
      inequalities in mortality in France, in both men and women. These findings
      highlight the need for greater attention to social determinants of health. The
      reduction of cardiovascular disease mortality in low educational level groups
      should be treated as a major public health priority.

PMID- 19088117
TI  - The value of presenting at scientific conferences: reflections by a couple of
      early career researchers.

PMID- 19088119
TI  - Are perceived neighbourhood problems associated with the likelihood of smoking?
AB  - OBJECTIVE: To explore associations between residents' perceptions of the local
      residential environment and the likelihood of their smoking. DESIGN: Using data
      (n = 2615) from the West of Scotland Twenty-07 Study, separately by gender, cross
      sectional associations between respondents' perceptions of neighbourhood
      (perceived absence of goods, incivilities and physical environmental problems)
      and the likelihood of being a current smoker and the amount smoked were examined.
      RESULTS: Perceived neighbourhood problems are associated with the likelihood of
      smoking but mainly among those with the most negative view of the local
      neighbourhood. Perceptions of the provision of neighbourhood amenities seems to
      be more strongly associated with women's than men's smoking status, whereas the
      perceived quality of the local neighbourhood appears to be a better predictor of
      men's smoking. CONCLUSIONS: Efforts to reduce smoking levels among more deprived
      groups may need to pay more attention to the role of local environmental
      conditions in influencing smoking behaviour.

PMID- 19088120
TI  - Recessive osteogenesis imperfecta caused by LEPRE1 mutations: clinical
      documentation and identification of the splice form responsible for prolyl 3
      hydroxylation.
AB  - BACKGROUND: Recessive forms of osteogenesis imperfecta (OI) may be caused by
      mutations in LEPRE1, encoding prolyl 3-hydroxylase-1 (P3H1) or in CRTAP, encoding
      cartilage associated protein. These proteins constitute together with cyclophilin
      B (CyPB) the prolyl 3-hydroxylation complex that hydroxylates the Pro986 residue
      in both the type I and type II collagen alpha1-chains. METHODS: We screened
      LEPRE1, CRTAP and PPIB (encoding CyPB) in a European/Middle Eastern cohort of 20
      lethal/severe OI patients without a type I collagen mutation. RESULTS: Four novel
      homozygous and compound heterozygous mutations were identified in LEPRE1 in four
      probands. Two probands survived the neonatal period, including one patient who is
      the eldest reported patient (17 7/12 years) so far with P3H1 deficiency. At
      birth, clinical and radiologic features were hardly distinguishable from those in
      patients with autosomal dominant (AD) severe/lethal OI. Follow-up data reveal
      that the longer lived patients develop a severe osteochondrodysplasia that
      overlaps with, but has some distinctive features from, AD OI. A new splice site
      mutation was identified in two of the four probands, affecting only one of three
      LEPRE1 mRNA splice forms, detected in this study. The affected splice form
      encodes a 736 amino acid (AA) protein with a "KDEL" endoplasmic reticulum
      retention signal. While western blotting and immunocytochemical analysis of
      fibroblast cultures revealed absence of this P3H1 protein, mass spectrometry and
      SDS-urea-PAGE data showed severe reduction of alpha1(I)Pro986 3-hydroxylation and
      overmodification of type I (pro)collagen chains in skin fibroblasts of the
      patients. CONCLUSION: These findings suggest that the 3-hydroxylation function of
      P3H1 is restricted to the 736AA splice form.

PMID- 19088121
TI  - Predicting the binding preference of transcription factors to individual DNA k
      mers.
AB  - MOTIVATION: Recognition of specific DNA sequences is a central mechanism by which
      transcription factors (TFs) control gene expression. Many TF-binding preferences,
      however, are unknown or poorly characterized, in part due to the difficulty
      associated with determining their specificity experimentally, and an incomplete
      understanding of the mechanisms governing sequence specificity. New techniques
      that estimate the affinity of TFs to all possible k-mers provide a new
      opportunity to study DNA-protein interaction mechanisms, and may facilitate
      inference of binding preferences for members of a given TF family when such
      information is available for other family members. RESULTS: We employed a new
      dataset consisting of the relative preferences of mouse homeodomains for all
      eight-base DNA sequences in order to ask how well we can predict the binding
      profiles of homeodomains when only their protein sequences are given. We
      evaluated a panel of standard statistical inference techniques, as well as
      variations of the protein features considered. Nearest neighbour among
      functionally important residues emerged among the most effective methods. Our
      results underscore the complexity of TF-DNA recognition, and suggest a rational
      approach for future analyses of TF families.

PMID- 19088122
TI  - A genetic programming-based approach to the classification of multiclass
      microarray datasets.
AB  - MOTIVATION: Feature selection approaches have been widely applied to deal with
      the small sample size problem in the analysis of micro-array datasets. For the
      multiclass problem, the proposed methods are based on the idea of selecting a
      gene subset to distinguish all classes. However, it will be more effective to
      solve a multiclass problem by splitting it into a set of two-class problems and
      solving each problem with a respective classification system. RESULTS: We propose
      a genetic programming (GP)-based approach to analyze multiclass microarray
      datasets. Unlike the traditional GP, the individual proposed in this article
      consists of a set of small-scale ensembles, named as sub-ensemble (denoted by
      SE). Each SE consists of a set of trees. In application, a multiclass problem is
      divided into a set of two-class problems, each of which is tackled by a SE first.
      The SEs tackling the respective two-class problems are combined to construct a GP
      individual, so each individual can deal with a multiclass problem directly.
      Effective methods are proposed to solve the problems arising in the fusion of
      SEs, and a greedy algorithm is designed to keep high diversity in SEs. This GP is
      tested in five datasets. The results show that the proposed method effectively
      implements the feature selection and classification tasks.

PMID- 19088123
TI  - Biallelic somatic and germline mutations in cerebral cavernous malformations
      (CCMs): evidence for a two-hit mechanism of CCM pathogenesis.
AB  - Cerebral cavernous malformations (CCMs) are vascular anomalies of the central
      nervous system, comprising dilated blood-filled capillaries lacking structural
      support. The lesions are prone to rupture, resulting in seizures or hemorrhagic
      stroke. CCM can occur sporadically, manifesting as solitary lesions, but also in
      families, where multiple lesions generally occur. Familial cases follow autosomal
      dominant inheritance due to mutations in one of three genes, CCM1/KRIT1,
      CCM2/malcavernin or CCM3/PDCD10. The difference in lesion burden between familial
      and sporadic CCM, combined with limited molecular data, suggests that CCM
      pathogenesis may follow a two-hit molecular mechanism, similar to that seen for
      tumor suppressor genes. In this study, we investigate the two-hit hypothesis for
      CCM pathogenesis. Through repeated cycles of amplification, subcloning and
      sequencing of multiple clones per amplicon, we identify somatic mutations that
      are otherwise invisible by direct sequencing of the bulk amplicon. Biallelic
      germline and somatic mutations were identified in CCM lesions from all three
      forms of inherited CCMs. The somatic mutations are found only in a subset of the
      endothelial cells lining the cavernous vessels and not in interstitial lesion
      cells. These data suggest that CCM lesion genesis requires complete loss of
      function for one of the CCM genes. Although widely expressed in the different
      cell types of the brain, these data also suggest a unique role for the CCM
      proteins in endothelial cell biology.

PMID- 19088124
TI  - A two-hit mechanism causes cerebral cavernous malformations: complete
      inactivation of CCM1, CCM2 or CCM3 in affected endothelial cells.
AB  - Cavernous vascular malformations occur with a frequency of 1:200 and can cause
      recurrent headaches, seizures and hemorrhagic stroke if located in the brain.
      Familial cerebral cavernous malformations (CCMs) have been associated with
      germline mutations in CCM1/KRIT1, CCM2 or CCM3/PDCD10. For each of the three CCM
      genes, we here show complete localized loss of either CCM1, CCM2 or CCM3 protein
      expression depending on the inherited mutation. Cavernous but not adjacent normal
      or reactive endothelial cells of known germline mutation carriers displayed
      immunohistochemical negativity only for the corresponding CCM protein but not for
      the two others. In addition to proving loss of function at the protein level, our
      data are the first to demonstrate endothelial cell mosaicism within cavernous
      tissues and provide clear pathogenetic evidence that the endothelial cell is the
      cell of disease origin.

PMID- 19088125
TI  - Altered visual function and interneuron survival in Atrx knockout mice: inference
      for the human syndrome.
AB  - ATRX is an SWI/SNF-like chromatin remodeling protein that is mutated in several X
      linked mental retardation syndromes, including the ATR-X syndrome. In mice, Atrx
      expression is widespread and attempts to understand its function in brain
      development are hampered by the lethality associated with ubiquitous or forebrain
      restricted ablation of this gene. One way to circumvent this problem is to study
      its function in a region of the brain that is dispensable for long-term survival
      of the organism. The retina is a well-characterized tractable model of CNS
      development and in our review of 202 ATR-X syndrome patients, we found ocular
      defects present in approximately 25% of the cases, suggesting that studying Atrx
      in this tissue will provide insight into function. We report that Atrx is
      expressed in the neuroprogenitor pool in embryonic retina and in all cell types
      of the mature retina with the exception of rod photoreceptors. Conditional
      inactivation of Atrx in the retina during embryogenesis ultimately results in a
      loss of only two types of neurons, amacrine and horizontal cells. We show that
      this defect does not arise from a failure to specify these cells but rather a
      defect in interneuron differentiation and survival post-natally. The timing of
      cell loss is concomitant with light-dependent changes in synaptic organization in
      the retina and with a change in Atrx subnuclear localization within these
      interneurons. Moreover, these interneuron defects are associated with functional
      deficits as demonstrated by reduced b-wave amplitudes upon electroretinogram
      analysis. These results implicate a role for Atrx in interneuron survival and
      differentiation.

PMID- 19088126
TI  - Mutant SOD1 impairs axonal transport of choline acetyltransferase and
      acetylcholine release by sequestering KAP3.
AB  - Mutations in the superoxide dismutase 1 (sod1) gene cause familial amyotrophic
      lateral sclerosis (FALS), likely due to the toxic properties of misfolded mutant
      SOD1 protein. Here we demonstrated that, starting from the pre-onset stage of
      FALS, misfolded SOD1 species associates specifically with kinesin-associated
      protein 3 (KAP3) in the ventral white matter of SOD1(G93A)-transgenic mouse
      spinal cord. KAP3 is a kinesin-2 subunit responsible for binding to cargos
      including choline acetyltransferase (ChAT). Motor axons in SOD1(G93A)-Tg mice
      also showed a reduction in ChAT transport from the pre-onset stage. By employing
      a novel FALS modeling system using NG108-15 cells, we showed that microtubule
      dependent release of acetylcholine was significantly impaired by misfolded SOD1
      species. Furthermore, such impairment was able to be normalized by KAP3
      overexpression. KAP3 was incorporated into SOD1 aggregates in human FALS cases as
      well. These results suggest that KAP3 sequestration by misfolded SOD1 species and
      the resultant inhibition of ChAT transport play a role in the dysfunction of ALS.

PMID- 19088127
TI  - The b2/b3 subdeletion shows higher risk of spermatogenic failure and higher
      frequency of complete AZFc deletion than the gr/gr subdeletion in a Chinese
      population.
AB  - Microdeletions in the azoospermia factor (AZF) regions on the long arm of the
      human Y chromosome are known to be associated with spermatogenic failure.
      Although AZFc is recurrently deleted in azoospermic or oligozoospermic males, no
      definitive conclusion has been reached for the contribution of different partial
      AZFc deletions to spermatogenic failure. To further investigate the roles of
      partial deletions in spermatogenic failure and the relationship between the
      complete and partial AZFc deletions, we performed deletion typing and Y
      chromosome haplogrouping in 756 idiopathic infertile Han-Chinese and 391 healthy
      Han-Chinese. We found that both the b2/b3 partial deletion and the DAZ3/4+CDY1a
      deletion pattern were associated with spermatogenic failure. We also confirmed
      that two previously reported fixations, the b2/b3 deletion in haplogroup N1 and
      the gr/gr deletion in haplogroup Q1. Remarkably, the frequency of the complete
      AZFc deletion in haplogroup N1 was significantly higher than that in the
      haplogroup Q1. These results suggest that the b2/b3 partial deletion was
      associated with a higher risk of complete AZFc deletion compared with the gr/gr
      partial deletion. Compared with the gr/gr deletion, the b2/b3 deletion presents a
      shorter distance among recombination targets and longer recombination substrates,
      which may be responsible for the increased incidence of subsequent recombination
      events that can lead to the complete AZFc deletion in this Chinese study
      population. The susceptibility of the b2/b3 partial deletion to the complete AZFc
      deletion deserves further investigation in larger and diverse populations,
      especially those with a relatively high frequency of b2/b3 and gr/gr partial
      deletions.

PMID- 19088128
TI  - Commentary: Cochrane review on ITNs for preventing malaria in pregnancy.

PMID- 19088129
TI  - Endovenous laser ablation (EVLA) in patients with varicose great saphenous vein
      (GSV) and incompetent saphenofemoral junction (SFJ): an ambulatory single center
      experience.
AB  - OBJECTIVES: To evaluate treatment results for varicose great saphenous vein (GSV)
      using endovenous laser ablation (EVLA) in an ambulatory single center. MATERIAL
      AND METHODS: We prospectively studied 77 limbs with varicose GSV in 74 patients
      who were treated using 980-nm EVL with a 600-mm laser fiber and the power
      settings of 10-25 Watts. The patients were followed using color Doppler
      ultrasound. RESULTS: Continued closure of treated GSV was found in 98.3% of the
      legs evaluated at 3-week follow-up (n = 60). At 3- and 6-month intervals, 94.1%
      and 97% successful occlusion was achieved, respectively. The main complications
      of the procedure included prolonged leg pain (2 cases), hyperestheasia (one case)
      and lidocaine sensitivity (one case). CONCLUSION: EVLA treatment of the GSV is a
      safe and highly effective method accompanied with few complications in midterm
      follow-up. It is feasible in ambulatory settings and the patients return to their
      daily activities early after intervention.

PMID- 19088130
TI  - Hybrid endovascular repair of an aneurysmal chronic type B dissection in a
      patient with Marfan syndrome with an aberrant right subclavian artery.
AB  - Abnormal aortic arch anatomy is relatively uncommon but most frequently involves
      an aberrant right subclavian artery. Rarely, it is associated with aneurysmal
      dilatation of a chronic type B dissection. Under such circumstances, the abnormal
      anatomy may complicate therapeutics options. Furthermore, controversy exists
      regarding the use of surgical or endovascular techniques in patients with aortic
      aneurysms and underlying arteriopathies. The current literature is limited with
      regard to reporting of the latter. We present a hybrid approach to repair such an
      aneurysm in a patient with Marfan syndrome. In a 2-stage procedure, involving
      initial supra-aortic bypass to all aortic arch branches, followed by endovascular
      stent graft deployment, the aneurysm was successfully excluded. There were no
      immediate complications and no evidence of endoleak at 3 months postoperatively,
      with thrombosis of the false lumen in the chest. By adapting hybrid open and
      endovascular techniques, complex thoracic aneurysms may be successfully treated
      in the short term in the presence of an underlying arteriopathy.

PMID- 19088131
TI  - Surgical versus endovascular reconstruction for chronic mesenteric ischemia: a
      contemporary UK series.
AB  - OBJECTIVE: To assess the outcome of surgical (SR) and endovascular (ER)
      reconstruction for chronic mesenteric ischemia (CMI). METHODS: Retrospective
      review of consecutive patients who underwent SR or ER for CMI in 3 UK vascular
      surgery units between 1996 and 2006. Early (<30 days; technical success,
      morbidity, mortality, length of hospital stay) and late (>30 days) outcomes
      (symptom recurrence, vessel/graft patency, reintervention, mortality) were
      assessed. RESULTS: A total of 27 patients underwent 32 reconstructions (SR = 17,
      ER = 15). A total of 44 of 56 (79%) diseased arteries underwent SR (n = 26;
      bypass = 24, reimplantation = 2; occlusion = 16, stenosis = 10) or ER (n = 18;
      stenosis = 16, occlusion = 2). Perioperative mortality for SR and ER was 6% and
      0%, respectively (P > or = .99). Hospital stay was shorter following ER (mean,
      4.3 vs. 14.2 days, P = .0003). Mean (range) follow-up for SR and ER was 34 (1-94)
      and 34 (0-135) months, respectively. At 2 years, SR demonstrated superior
      secondary patency (100% vs. 65%) and clinical patency (100% vs. 73%).
      CONCLUSIONS: Surgical mesenteric reconstruction is associated with significantly
      longer hospital stay, but superior long-term outcome compared to endovascular
      reconstruction.

PMID- 19088132
TI  - EVAR in small versus large aneurysms: does size influence outcome?
AB  - OBJECTIVE: To determine whether there is a difference in outcome between
      endovascular repair of abdominal aortic aneurysm (EVAR) of small versus large
      aneurysms. METHODS: A total of 192 patients from the Power-link trial were
      subdivided into small abdominal aortic aneurysms (AAA; </=5 cm) and large AAA (>5
      cm) groups. Demographics, perioperative morbidity, mortality, overall survival,
      and freedom from major adverse events, endoleak, aneurysm-related death,
      migration, and secondary procedures were assessed. Aneurysmal involvement of the
      iliacs as well as neck length and angulation was compared between groups.
      RESULTS: Perioperative morbidity (P = 1.000), mortality (P = .4603), and extent
      of iliac involvement did not differ between groups (P = .2260). The necks in
      small AAA were longer (P = .0028) and less angulated (P < .0001). There was no
      difference in overall survival (P = .6066), freedom from major adverse events (P
      = .7842), endoleak, (P = .1832), migration (P = .5765), aneurysm-related death (P
      = .4728), or need for secondary procedures (P = .2323). CONCLUSION: Under
      controlled conditions of patient and device selection, there is no significant
      difference in outcome for EVAR of small versus large AAA.

PMID- 19088133
TI  - Proprioception and muscle torque deficits in children with hypermobility
      syndrome.
AB  - OBJECTIVES: Sensorimotor deficits such as impaired joint proprioception and
      muscle weakness have been found in association with hypermobility syndrome (HMS)
      in adults. HMS is more common in children than adults, yet such deficits have not
      been adequately investigated in paediatric populations. It is therefore uncertain
      as to what sensorimotor deficits are present in children with HMS. This study
      investigated knee joint proprioception and muscle torque in healthy children and
      those with HMS. METHODS: Thirty-seven healthy children (mean age +/- s.d. = 11.5
      +/- 2.6 yrs) and 29 children with HMS (mean age +/- s.d. = 11.9 +/- 1.8 yrs)
      participated in this study. Knee joint kinaesthesia (JK) and joint position sense
      (JPS) were measured, with the absolute angular error (AAE) calculated as the
      absolute difference between the target and perceived angles. Knee extensor and
      flexor muscle torque was assessed and normalized to body mass. Mann-Whitney U
      tests were performed to compare JK, JPS and muscle torque between the two groups.
      RESULTS: Children with HMS had significantly poorer JK and JPS compared with the
      controls (both P < 0.001). Knee extensor and flexor muscle torque was also
      significantly reduced (both P < 0.001) in children with HMS compared with their
      healthy counterparts. CONCLUSIONS: The findings of this study demonstrated that
      knee joint proprioception was impaired in children with HMS. They also had weaker
      knee extensor and flexor muscles than healthy controls. Clinicians should be
      aware of these identified deficits in children with HMS, and a programme of
      proprioceptive training and muscle strengthening may be indicated.

PMID- 19088134
TI  - PSI-BLAST pseudocounts and the minimum description length principle.
AB  - Position specific score matrices (PSSMs) are derived from multiple sequence
      alignments to aid in the recognition of distant protein sequence relationships.
      The PSI-BLAST protein database search program derives the column scores of its
      PSSMs with the aid of pseudocounts, added to the observed amino acid counts in a
      multiple alignment column. In the absence of theory, the number of pseudocounts
      used has been a completely empirical parameter. This article argues that the
      minimum description length principle can motivate the choice of this parameter.
      Specifically, for realistic alignments, the principle supports the practice of
      using a number of pseudocounts essentially independent of alignment size.
      However, it also implies that more highly conserved columns should use fewer
      pseudocounts, increasing the inter-column contrast of the implied PSSMs. A new
      method for calculating pseudocounts that significantly improves PSI-BLAST's;
      retrieval accuracy is now employed by default.

PMID- 19088136
TI  - The cult of the conference bag.

PMID- 19088135
TI  - Paracrine effects of uterine leucocytes on gene expression of human uterine
      stromal fibroblasts.
AB  - The endometrium contains a distinct population of immune cells that undergo
      cyclic changes during the menstrual cycle and implantation. The majority of these
      leucocytes are uterine NK (uNK) cells, however how these cells interact with
      uterine stromal fibroblasts remains unclear. We therefore investigated the
      paracrine effect of medium conditioned by uterine decidual leucocytes (which are
      enriched for uNK cells) on the gene expression profile of endometrial stromal
      fibroblasts in vitro using a cDNA microarray. Our results, verified by real-time
      PCR, ELISA and FACS analysis, reveal that soluble factors from uterine leucocytes
      substantially alter endometrial stromal fibroblast gene expression. The largest
      group of up-regulated genes found was chemokines and cytokines. These include IL
      8, CCL8 and CXCL1, which have also been shown to be stimulated by contact of
      stromal fibroblasts with trophoblast, suggesting that uNK cells work
      synergistically to support trophoblast migration during implantation. The
      decidual leucocytes also up-regulated IL-15 and IL-15Ralpha in stromal
      fibroblasts which could produce a niche for uNK cells allowing proliferation
      within and recruitment into the uterus, as seen in bone marrow. Overall this
      study demonstrates, for the first time, the paracrine communication between
      uterine leucocytes and uterine stromal fibroblasts, and adds to the understanding
      of how the uterine immune system contributes to the changes seen within the
      cycling endometrium.

PMID- 19088137
TI  - Billy Bunter and the obesogenic environment.

PMID- 19088138
TI  - Asylum seekers in detention centres receive poor medical care, MP says.

PMID- 19088139
TI  - Proposal to allow drug companies to give information to public sparks outcry.

PMID- 19088140
TI  - Right-left discrimination among medical students: questionnaire and psychometric
      study.
AB  - OBJECTIVE: To determine medical students' self awareness and ability to
      discriminate right from left; to identify characteristics associated with this
      ability; and to identify any techniques used to aid discrimination. DESIGN:
      Questionnaire and psychometric study. SETTING: Undergraduate medical school,
      Northern Ireland. PARTICIPANTS: 290 first year undergraduate students. MAIN
      OUTCOME MEASURE: Medical students' ability to discriminate right from left using
      the Bergen right-left discrimination test. RESULTS: Test scores ranged from 31 to
      143 on a scale of 0-144 (mean 112 (standard deviation 22.2)). Male students
      significantly outperformed female students (117.18 (26.96) v 110.80 (28.94)).
      Students who wanted to be surgeons performed significantly better than those who
      wanted to be general practitioners or medical doctors (119.87 (25.15) v 110.55
      (27.36) v 112.50 (26.88)). The interaction effect for sex and career wishes was
      not significant (P=0.370). Students who used learnt techniques to help them
      discriminate scored significantly less than those who did not (P<0.001). Students
      had greater difficulty in discriminating right from left when looking at the
      forward view rather than the back view (P<0.001). CONCLUSIONS: Male students were
      better than female students at distinguishing right from left, and aspiring
      surgeons were better than aspiring general practitioners or medical doctors.
      Students had more difficulty with the forward view than the back view.

PMID- 19088141
TI  - Learning from emergencies.

PMID- 19088142
TI  - The left handed surgical trainee.

PMID- 19088143
TI  - Fantastic feeding funnels.

PMID- 19088144
TI  - Reappraising florence nightingale.

PMID- 19088146
TI  - Not what we used to be?

PMID- 19088147
TI  - Left-right discrimination in medicine.

PMID- 19088148
TI  - Monitoring is vital for government's end of life care strategy to be successful.

PMID- 19088149
TI  - Pharmacists are to offer the pill in London pilot scheme.

PMID- 19088150
TI  - Iodine deficiency in pregnancy and the effects of maternal iodine supplementation
      on the offspring: a review.
AB  - The World Health Organization (WHO) recently increased their recommended iodine
      intake during pregnancy from 200 to 250 microg/d and suggested that a median
      urinary iodine (UI) concentration of 150-249 microg/L indicates adequate iodine
      intake in pregnant women. Thyrotropin concentrations in blood collected from
      newborns 3-4 d after birth may be a sensitive indicator of even mild iodine
      deficiency during late pregnancy; a <3% frequency of thyrotropin values >5 mU/L
      indicates iodine sufficiency. New reference data and a simple collection system
      may facilitate use of the median UI concentration as an indicator of iodine
      status in newborns. In areas of severe iodine deficiency, maternal and fetal
      hypothyroxinemia can cause cretinism and adversely affect cognitive development
      in children; to prevent fetal damage, iodine should be given before or early in
      pregnancy. Whether mild-to-moderate maternal iodine deficiency produces more
      subtle changes in cognitive function in offspring is unclear; no controlled
      intervention studies have measured long-term clinical outcomes. Cross-sectional
      studies have, with few exceptions, reported impaired intellectual function and
      motor skills in children from iodine-deficient areas, but many of these studies
      were likely confounded by other factors that affect child development. In
      countries or regions where <90% of households are using iodized salt and the
      median UI concentration in school-age children is <100 microg/L, the WHO
      recommends iodine supplementation in pregnancy and infancy.

PMID- 19088151
TI  - Can a small-changes approach help address the obesity epidemic? A report of the
      Joint Task Force of the American Society for Nutrition, Institute of Food
      Technologists, and International Food Information Council.
AB  - The continued rise in obesity rates in most countries suggests that current
      programs and initiatives designed to combat obesity have not been successful in
      reversing the obesity epidemic. Obesity rates are increasing because of a gradual
      weight gain in most populations. There has been little long-term success in
      treating established obesity through lifestyle change, perhaps because of the
      large permanent changes in diet and physical activity required to keep weight
      off. An alternative strategy to address the obesity epidemic involves not
      focusing on weight loss but promoting small changes in diet and physical activity
      to initially prevent further weight gain. With the use of this strategy, obesity
      rates could first be stabilized in most populations and then, over time, decrease
      gradually. Supporting data show that small reductions in conscious energy intake
      and increases in physical activity can reduce excessive weight gain. The
      opportunity exists to use the small-changes approach to bring different
      stakeholders together to create a national initiative to address the global
      epidemic of obesity. The Joint Task Force of the American Society for Nutrition,
      Institute of Food Technologists, and International Food Information Council
      believe that a small-changes framework, aimed at helping people make conscious
      small changes in lifestyle behaviors, in combination with efforts by the private
      sector to gradually "ratchet down" some of the environmental factors that have
      contributed to excessive energy intake and the declining rates of physical
      activity, can be successful in reducing obesity rates. Such an initiative would
      benefit from the support of educational and social marketing campaigns developed
      with governmental input and support.

PMID- 19088153
TI  - Hepcidin compared with prohepcidin: an absorbing story.

PMID- 19088152
TI  - Glycemic index, glycemic load, and risk of digestive tract neoplasms: a
      systematic review and meta-analysis.
AB  - BACKGROUND: Habitual consumption of diets with a high glycemic index (GI) and a
      high glycemic load (GL) may influence cancer risk via hyperinsulinemia and the
      insulin-like growth factor axis. OBJECTIVE: The objective was to conduct a
      systematic review to assess the association between GI, GL, and risk of digestive
      tract cancers. DESIGN: Medline and Embase were searched for relevant publications
      from inception to July 2008. When possible, adjusted results from a comparison of
      cancer risk of the highest compared with the lowest category of GI and GL intake
      were combined by using random-effects meta-analyses. RESULTS: Cohort and case
      control studies that examined the risk between GI or GL intake and colorectal
      cancer (n = 12) and adenomas (n = 2), pancreatic cancer (n = 6), gastric cancer
      (n = 2), and squamous-cell esophageal carcinoma (n = 1) were retrieved. Most case
      control studies observed positive associations between GI and GL intake and these
      cancers. However, pooled cohort study results showed no associations between
      colorectal cancer risk and GI intake [relative risk (RR): 1.04; 95% CI: 0.92,
      1.12; n = 7 studies] or GL intake (RR: 1.06; 95% CI: 0.95, 1.17; n = 8 studies).
      Furthermore, no significant associations were observed in meta-analyses of cohort
      study results of colorectal cancer subsites and GI and GL intake. Similarly, no
      significant associations emerged between pancreatic cancer risk and GI intake
      (RR: 0.99; 95% CI: 0.83, 1.19; n = 5 studies) or GL intake (RR: 1.01; 95% CI:
      0.86, 1.19; n = 6 studies) in combined cohort studies. CONCLUSIONS: The findings
      from our meta-analyses indicate that GI and GL intakes are not associated with
      risk of colorectal or pancreatic cancers. There were insufficient data available
      regarding other digestive tract cancers to make any conclusions about GI or GL
      intake and risk.

PMID- 19088154
TI  - Overview of gefitinib in non-small cell lung cancer: an Asian perspective.
AB  - Clinical experience with the EGFR-TKI gefitinib in Asian patients with NSCLC will
      be reviewed, both in patients who have previously failed chemotherapy and in the
      first-line setting (gefitinib is currently not licensed for first-line
      treatment). Tolerability and specific adverse events in patients of Asian origin
      will be discussed. Differing objective response rates between patients of Asian
      and non-Asian origin when treated with gefitinib (and standard cytotoxics) will
      also be discussed along with EGFR mutations and drug resistance. Reports of Phase
      II/III clinical experience with gefitinib 250 mg/day in Asia were identified by
      searching in Medline and ASCO databases for publications between 1993 and 2008.
      Defined search criteria included (gefitinib OR Iressa OR ZD1839) AND NSCLC AND
      (Asia OR Japan OR China OR Taiwan OR Korea) or 'Clinical trial' type, with
      additional searches, including AND 'interstitial lung disease (ILD)' or 'EGFR
      mutation'. Numerous Phase II/III trials including patients of Asian origin with
      previously treated advanced NSCLC report a consistent clinical benefit of
      gefitinib. Gefitinib is generally well tolerated by patients with NSCLC although
      the incidence of ILD in Japanese patients must be noted. Studies analyzing EGFR
      mutations indicate that these mutations occur at a much higher rate in patients
      of Asian origin than in non-Asian patients. Data from several studies indicate
      that EGFR mutation-positive patients of Asian origin have better efficacy
      outcomes with first-line gefitinib when compared with those who are EGFR mutation
      negative. Research is ongoing to evaluate the role of tailoring patients'
      treatment according to their genetic phenotype.

PMID- 19088155
TI  - Evaluation and management of adult hypoglycemic disorders: an Endocrine Society
      Clinical Practice Guideline.
AB  - OBJECTIVE: The aim is to provide guidelines for the evaluation and management of
      adults with hypoglycemic disorders, including those with diabetes mellitus.
      EVIDENCE: Using the recommendations of the Grading of Recommendations,
      Assessment, Development and Evaluation (GRADE) system, the quality of evidence is
      graded very low (plus sign in circle ooo), low (plus sign in circle plus sign in
      circle oo), moderate (plus sign in circle plus sign in circle plus sign in circle
      o), or high (plus sign in circle plus sign in circle plus sign in circle plus
      sign in circle). CONCLUSIONS: We recommend evaluation and management of
      hypoglycemia only in patients in whom Whipple's triad--symptoms, signs, or both
      consistent with hypoglycemia, a low plasma glucose concentration, and resolution
      of those symptoms or signs after the plasma glucose concentration is raised--is
      documented. In patients with hypoglycemia without diabetes mellitus, we recommend
      the following strategy. First, pursue clinical clues to potential hypoglycemic
      etiologies--drugs, critical illnesses, hormone deficiencies, nonislet cell
      tumors. In the absence of these causes, the differential diagnosis narrows to
      accidental, surreptitious, or even malicious hypoglycemia or endogenous
      hyperinsulinism. In patients suspected of having endogenous hyperinsulinism,
      measure plasma glucose, insulin, C-peptide, proinsulin, beta-hydroxybutyrate, and
      circulating oral hypoglycemic agents during an episode of hypoglycemia and
      measure insulin antibodies. Insulin or insulin secretagogue treatment of diabetes
      mellitus is the most common cause of hypoglycemia. We recommend the practice of
      hypoglycemia risk factor reduction--addressing the issue of hypoglycemia,
      applying the principles of intensive glycemic therapy, and considering both the
      conventional risk factors and those indicative of compromised defenses against
      falling plasma glucose concentrations--in persons with diabetes.

PMID- 19088156
TI  - Thyroid volume in hypothyroidism due to autoimmune disease follows a unimodal
      distribution: evidence against primary thyroid atrophy and autoimmune thyroiditis
      being distinct diseases.
AB  - CONTEXT: Primary overt autoimmune hypothyroidism is often divided into primary
      idiopathic hypothyroidism with thyroid atrophy (Ord's disease) and hypothyroidism
      with goitre (Hashimoto's disease). OBJECTIVE: The aim of the present study was to
      characterize the two subtypes of disease. DESIGN AND SETTING: This was a
      population-based study identifying patients newly diagnosed with overt autoimmune
      hypothyroidism. PATIENTS: We prospectively identified all patients with incident
      overt autoimmune hypothyroidism in a Danish population cohort, and 247 patients
      were invited to join a comprehensive program including thyroid ultrasonography
      and measurements of thyroid autoantibodies. Of the 144 patients investigated (58%
      of all invited), 139 were compared with 556 sex-, age-, and region-matched
      controls from the cohort. RESULTS: Patients had lower median (11.6 ml vs. 13.5
      ml, P = 0.001) and a more dispersed distribution of thyroid volumes compared with
      controls (P < 0.001). Log thyroid volume showed a Gaussian distribution in both
      males and females with no bimodal pattern. Nearly all patients had measurable
      thyroid autoantibodies, but with increasing thyroid volume (quartile I, II, III,
      and IV), levels of circulating antibodies were higher (median thyroid peroxidase
      autoantibody 1540, 3122, 4686, and 7058 kU/liter; median thyroglobulin
      autoantibody 72, 143, 119, and 1195 kU/liter), and thyroid volume correlated
      negatively with echogenicity (r = -0.21, P = 0.011). Patients with the smallest
      volumes were biochemically more hypothyroid at diagnosis (median serum T(4) 21.0,
      45.5, 45.0, and 36.7 nmol/liter; median serum TSH 81.0, 40.9, 45.4, and 55.6
      mU/liter). No difference between groups was observed in prevalence of TSH
      receptor autoantibody (14.7, 5.6, 14.7, and 8.3%) or duration of symptoms before
      hypothyroidism was diagnosed. CONCLUSIONS: In primary autoimmune hypothyroidism,
      thyroid volume follows a normal distribution. Cases with thyroid atrophy and
      goiter are only extremes within this distribution and do not represent separate
      disorders. However, patients with low vs. high thyroid volume differ with
      respects to several characteristics.

PMID- 19088157
TI  - Hepatic lipase, genetically elevated high-density lipoprotein, and risk of
      ischemic cardiovascular disease.
AB  - CONTEXT: Hepatic lipase influences metabolism of high-density lipoprotein (HDL),
      a risk factor for ischemic cardiovascular disease (ICD: ischemic heart disease
      and ischemic cerebrovascular disease). OBJECTIVE: We tested the hypothesis that
      genetic variation in the hepatic lipase genetic variants V73M, N193S, S267F,
      L334F, T383M, and -480c>t influence levels of lipids, lipoproteins, and
      apolipoproteins and risk of ICD. DESIGN: For the cross-sectional study, we
      genotyped 9003 individuals from the Copenhagen City Heart Study; hereof were 8971
      individuals included in the prospective study, 1747 of whom had incident ICD
      during 28 yr of follow-up. For the case-control studies, 2110 ischemic heart
      disease patients vs. 4899 controls and 769 ischemic cerebrovascular disease
      patients vs. 2836 controls, respectively, were genotyped. Follow-up was 100%
      complete. RESULTS: HDL cholesterol was higher by 0.21 mmol/liter in S267F
      heterozygotes, by 0.06 mmol/liter in -480c>t heterozygotes, and by 0.13
      mmol/liter in -480c>t homozygotes, as compared with noncarriers. These HDL
      increases theoretically predicted hazard ratios for ICD of 0.87 [95% confidence
      interval (CI) 0.84-0.90], 0.96 (95% CI 0.95-0.97), and 0.91 (95% CI 0.89-0.94),
      respectively; this calculation assumes that genetically elevated HDL levels
      confer decreased risk similar to common HDL elevations. In contrast, when all
      cases and controls were combined, the observed odds ratios for ICD for these
      three genetic variants vs. noncarriers were 1.19 (0.76-1.88), 1.04 (0.96-1.13),
      and 1.08 (0.89-1.30), respectively. Hazard/odds ratios for ICD in carriers vs.
      noncarriers of the four remaining hepatic lipase genetic variants did not differ
      consistently from 1.0. CONCLUSION: Hepatic lipase genetic variants with elevated
      levels of HDL cholesterol did not associate with risk of ICD.

PMID- 19088158
TI  - Increased production of 17beta-estradiol in endometriosis lesions is the result
      of impaired metabolism.
AB  - CONTEXT: substantial evidence suggests that the expression of steroid
      metabolizing enzymes in endometriosis is altered, turning the ectopic endometrium
      into a source of 17beta-estradiol. However, whether these differences result in a
      net increase in local 17beta-estradiol production/activity has not been shown.
      SUBJECTS AND METHODS: The activities of the most important steroidogenic enzymes
      synthesizing and inactivating 17beta-estradiol were determined by HPLC in matched
      eutopic and ectopic tissue from patients with endometriosis (n = 14) and in
      endometrium from controls (n = 20). RESULTS: Aromatase activity is negligible in
      the ectopic endometrium, whereas the activity of estrogen sulfatase is high
      though not different between ectopic, eutopic and control endometrium. The
      activity of 17beta-hydroxysteroid dehydrogenases (17beta-HSDs) converting estrone
      into 17beta-estradiol is higher in the ectopic compared to the eutopic
      endometrium in patients. The activity of 17beta-HSDs converting 17beta-estradiol
      back to estrone is significantly lower in the ectopic compared to the eutopic
      endometrium of both patients and controls. To evaluate the net metabolic capacity
      of tissues to synthesize 17beta-estradiol, we calculated the activity ratio
      between 17beta-HSDs synthesizing versus 17beta-HSDs inactivating 17beta
      estradiol. This ratio is significantly higher in the ectopic compared to the
      eutopic endometrium of patients and controls, indicating a high synthesis of
      17beta-estradiol in the ectopic locations. This is further supported by the
      elevated mRNA levels of the estrogen-responsive gene TFF1 in all ectopic compared
      to eutopic endometria. CONCLUSION: Endometriotic lesions have higher production
      of 17beta-estradiol than the eutopic endometrium of patients and controls. This
      is mostly the result of impaired metabolism.

PMID- 19088160
TI  - Effects of insulin and glucose on cellular metabolic fluxes in homocysteine
      transsulfuration, remethylation, S-adenosylmethionine synthesis, and global
      deoxyribonucleic acid methylation.
AB  - BACKGROUND: The mechanisms underlying the impact of pathophysiological elevations
      in insulin or glucose on hepatic cellular homocysteine kinetics is not fully
      understood. OBJECTIVE: The objective of the study was to investigate the impact
      of elevated insulin/glucose on hepatic homocysteine kinetics at the cellular
      level. DESIGN AND METHODS: Effects of insulin and glucose on homocysteine
      remethylation and transsulfuration metabolic fluxes were investigated in a cell
      model using stable isotopic tracers and gas chromatography/mass spectrometry. The
      methylation status was assessed by S-adenosylmethionine (adoMet), the adoMet to S
      adenosylhomocysteine ratio, DNA methyltransferase activity, and methylated
      cytidine content of DNA. The expression profile of homocysteine remethylation,
      transmethylation, and transsulfuration-associated genes was determined. RESULTS:
      Insulin increased cellular homocysteine production primarily by its inhibition of
      transsulfuration. When cells were exposed to elevated insulin and glucose,
      homocysteine remethylation was enhanced, which consequently increased
      intracellular adoMet concentrations by inducing adoMet synthase activity.
      Elevated glucose further enhanced DNA methyltransferase activity that
      subsequently led to increased global DNA methylation. CONCLUSIONS: We
      demonstrated the novel finding of a direct promoting effect of high cellular
      insulin or glucose exposure on homocysteine remethylation, adoMet synthase
      activity, and adoMet synthesis. We also provided new evidence indicating that
      when hepatic tissue is exposed to elevated insulin or glucose, the cellular
      methylation balance can be altered, which may have potential epigenetic impacts
      gene regulation in diabetic individuals. These findings in a cell line may or may
      not reflect what happens in humans. In vivo studies on the homocysteine
      transmethylation fluxes and DNA methylation in diabetic state are underway.

PMID- 19088159
TI  - Aromatase and 5alpha-reductase inhibition during an exogenous testosterone clamp
      unveils selective sex steroid modulation of somatostatin and growth hormone
      secretagogue actions in healthy older men.
AB  - BACKGROUND: How endogenous testosterone (Te), 5alpha-dihydrotestosterone (DHT),
      and estradiol (E(2)) regulate pulsatile GH secretion is not understood.
      HYPOTHESIS: Conversion of Te to androgenic (Te-->DHT) or estrogenic (Te-->E(2))
      products directs GH secretion. SUBJECTS AND LOCATION: Healthy older men (N = 42,
      ages 50-79 yr) participated at an academic medical center. METHODS: We inhibited
      5alpha-reduction with dutasteride and aromatization with anastrozole during a
      pharmacological Te clamp and infused somatostatin (SS), GHRH, GH-releasing
      peptide-2 (GHRP-2), and L-arginine/GHRH/GHRP-2 (triple stimulus) to modulate GH
      secretion. ENDPOINTS: Deconvolution-estimated basal and pulsatile GH secretion
      was assessed. RESULTS: Administration of Te/placebo elevated Te by 2.8-fold, DHT
      by 2.6-fold, and E(2) concentrations by 1.9-fold above placebo/placebo.
      Te/dutasteride and Te/anastrozole reduced stimulated DHT and E(2) by 89 and 86%,
      respectively. Stepwise forward-selection regression analysis revealed that 1) Te
      positively determines mean (P = 0.017) and peak (P < 0.001) GH concentrations,
      basal GH secretion (P = 0.015), and pulsatile GH secretion stimulated by GHRP-2
      (P < 0.001); 2) Te and E(2) jointly predict GH responses to the triple stimulus
      (positively for Te, P = 0.006, and negatively for E(2), P = 0.031); and 3) DHT
      correlates positively with pulsatile GH secretion during SS infusion (P = 0.011).
      These effects persisted when abdominal visceral fat was included in the
      regression. CONCLUSION: The present outcomes suggest a tetrapartite model of GH
      regulation in men, in which systemic concentrations of Te, DHT, and E(2) along
      with abdominal visceral fat determine the selective actions of GH secretagogues
      and SS.

PMID- 19088161
TI  - A common deletion in the uridine diphosphate glucuronyltransferase (UGT) 2B17
      gene is a strong determinant of androgen excretion in healthy pubertal boys.
AB  - BACKGROUND: Testosterone (T) is excreted in urine as water-soluble glucuronidated
      and sulfated conjugates. The ability to glucuronidate T and other steroids
      depends on a number of different glucuronidases (UGT) of which UGT2B17 is
      essential. The aim of the study was to evaluate the influence of UGT2B17
      genotypes on urinary excretion of androgen metabolites in pubertal boys. STUDY
      DESIGN: A clinical study of 116 healthy boys aged 8-19 yr. UGT2B17 genotyping was
      performed using quantitative PCR. Serum FSH, LH, T, estradiol (E2), and SHBG were
      analyzed by immunoassays, and urinary levels of androgen metabolites were
      quantitated by gas chromatography/mass spectrometry in all subjects. RESULTS: Ten
      of 116 subjects (9%) presented with a homozygote deletion of the UGT2B17 gene
      (del/del), whereas 52 and 54 boys were hetero- and homozygous carriers of the
      UGT2B17 gene (del/ins and ins/ins), respectively. None of the reproductive
      hormones were affected by UGT2B17 genotype. In all subjects, mean urinary
      T/epitestosterone ratio was 1.56 [1.14 (SD); 0.1-6.9 (range)] and unaffected by
      age or pubertal stage. Subjects with homozygous deletions of UGT2B17 had
      significantly lower urinary levels of T and 5alpha- and 5beta-androstanediol.
      Mean urinary T/epitestosterone was significantly reduced in del/del subjects
      [0.29 (0.30); 0.1-1.0 (range), P < 0.0001]. CONCLUSION: In pubertal boys, a
      common homozygous deletion in the UGT2B17 gene strongly affected urinary
      excretion pattern of androgen metabolites but did not influence circulating
      androgen levels.

PMID- 19088163
TI  - Procalcitonin: a marker for the diagnosis and follow-up of patients with
      medullary thyroid carcinoma.
AB  - CONTEXT: Calcitonin (CT) is the main medullary thyroid carcinoma (MTC) tumor
      marker. However, it has several limitations, including a concentration-dependent
      biphasic half-life, sensitivity to rapid in vitro degradation, and the presence
      of different isoforms/fragments. Procalcitonin (PCT), the prohormone of
      calcitonin, is free of these limitations but is currently used only as a sepsis
      marker. OBJECTIVES: The objective of the study was to determine whether PCT is
      suited as a MTC tumor marker by comparing the diagnostic performance of PCT with
      that of CT in MTC. DESIGN: PCT and CT were measured in a total of 835 subjects,
      including normal volunteers (n = 197) and patients with active-MTC (n = 91),
      cured-MTC (n = 42), neuroendocrine tumors (n = 225), mastocytosis (n = 48),
      follicular cell-derived thyroid carcinoma (cured = 120, persistent/recurrent =
      55), and benign thyroid disease (n = 57). RESULTS: PCT levels were significantly
      higher in the active-MTC patients (mean 126.4 ng/ml) than the cured-MTC patients
      (mean <0.1 ng/ml). The overall concordance between the two markers was 95.7%
      (kappa = 0.81). Receiver-operating characteristic curve analysis showed no
      significant difference in diagnostic performance between CT and PCT. PCT's
      diagnostic sensitivity and specificity were 91 and 96%, respectively. The
      corresponding values for CT were 99 and 98%. Analyte stability studies showed
      that CT is very unstable in vitro with a decrease of 35-50% from the original
      value 24 h after the blood draw, whereas PCT levels did not significantly change
      during this time. CONCLUSIONS: A strong correlation was observed between PCT and
      CT levels in patients with MCT. Given PCT's greater analytical stability, we
      conclude that it represents a promising complementary MTC tumor marker.

PMID- 19088162
TI  - The effect of diurnal variation on clinical measurement of serum testosterone and
      other sex hormone levels in men.
AB  - CONTEXT: Although diurnal variation of testosterone and other hormones in men has
      been well documented, the effect of this variation on sampling during typical
      clinic hours has not been examined. OBJECTIVE: Our objective was to examine
      temporal variation in serum testosterone and five other hormones in men over
      normal clinic hours. DESIGN: Blood samples were collected at six separate visits,
      three morning visits 1-3 d apart and three afternoon visits 1-3 d apart. SETTING
      AND PARTICIPANTS: In Boston, MA, 66 men participated, 30-80 yr of age, randomly
      selected from the Boston Area Community Health Survey who completed at least five
      visits. MAIN OUTCOME MEASURES: The age-specific ratio of hormone level at times
      ranging from 0801-1600 h to hormone level at 0800 h was calculated. Ratios were
      calculated from parameter estimates obtained from cosinor models. RESULTS: In men
      30-40 yr old, testosterone levels were 20-25% lower at 1600 h than at 0800 h. The
      difference declined with age, with a 10% difference at 70 yr. 17 men with at
      least one of three measurements less than 300 ng/dl (10.4 nmol/liter) after 1200
      h had normal testosterone levels at all three visits before 1200 h (five of eight
      men 30-47 yr old, four of nine men 66-80 yr old). Much lower levels of diurnal
      variation were found for dihydrotestosterone, SHBG, LH, FSH, and estradiol at all
      ages. CONCLUSIONS: Our results support the recommendation of restricting
      testosterone measurements to morning hours in both young and older men. Limited
      diurnal variation in other hormones indicates that sampling through the day is
      appropriate.

PMID- 19088164
TI  - Ten years of growth hormone (GH) replacement normalizes muscle strength in GH
      deficient adults.
AB  - CONTEXT: GH replacement for 1-5 yr improves, but does not fully normalize, muscle
      strength. OBJECTIVE, DESIGN, AND PATIENTS: In this single-center, open-labeled,
      prospective study, the effects of 10 yr of GH replacement on muscle strength and
      neuromuscular function were followed in 109 consecutive adults (61 men; mean age
      50.0 yr; range 22-74 yr) with adult-onset GH deficiency. RESULTS: The mean
      initial GH dose of 0.88 mg/d was gradually lowered to 0.47 mg/d. The mean IGF-I
      sd score increased from -1.54 at baseline to 1.12 at study end. GH replacement
      induced a sustained increase in lean mass and isometric knee flexor strength (60
      degrees). In most other measures of upper leg and handgrip strength, there were
      transient increases during the first half of the study (0-5 yr), whereas during
      the second half (5-10 yr), the absolute values of muscle strength decreased and
      returned to or even below the baseline values. However, after correction for age
      and gender using observed/predicted value ratios, there were sustained and, until
      7 yr, even progressive increases in the measures of muscle strength. At study
      end, knee flexor strength had increased to 104-110% of predicted, knee extensor
      strength to 93-108%, and handgrip strength to 88-93%. Measurements of
      neuromuscular function showed reduced voluntary motor unit activation after 10
      yr. CONCLUSIONS: Ten years of GH replacement therapy increased muscle strength
      during the first half of the study and thereafter partly protected against the
      normal age-related decline in muscle strength and neuromuscular function,
      resulting in approximately normalized muscle strength after 10 yr.

PMID- 19088165
TI  - Association between serum osteocalcin and markers of metabolic phenotype.
AB  - CONTEXT: Osteocalcin has been reported to contribute to the regulation of glucose
      tolerance and insulin secretion and sensitivity in experimental animals.
      OBJECTIVE: Our objective was to examine the association between serum osteocalcin
      concentration and markers of dysmetabolic phenotype using data from a completed
      clinical trial in adults age 65 and older [n = 380, mean age 71 yr, body mass
      index (BMI) 26.9 kg/m(2), 5% with diabetes]. RESEARCH DESIGN AND METHODS: In
      cross-sectional analyses (baseline data), we estimated the associations of serum
      osteocalcin and urine N-telopeptide with markers of metabolic phenotype including
      fasting plasma glucose (FPG) (primary outcome), fasting insulin, insulin
      sensitivity estimated by homeostasis model assessment for insulin resistance,
      plasma high-sensitivity C-reactive protein, IL-6, and measures of adiposity (BMI
      and body fat) (secondary outcomes) after multivariate adjustment for potential
      confounders. In prospective analysis (placebo arm), we estimated the associations
      of osteocalcin and N-telopeptide with change in the primary outcome, FPG, over a
      3-yr period. RESULTS: In cross-sectional analyses, serum osteocalcin
      concentration was inversely associated with FPG (P = 0.01), fasting insulin (P =
      0.006), homeostasis model assessment for insulin resistance (P = 0.002), high
      sensitivity C-reactive protein (P = 0.01), IL-6 (P = 0.02), BMI (P < 0.001), and
      body fat (P < 0.001). When participants were divided into tertiles by serum
      osteocalcin, mean FPG was 97.1 vs. 104.8 mg/dl in the highest vs. lowest
      osteocalcin tertile, respectively (P < 0.01). In prospective analyses, exposure
      to higher osteocalcin levels during follow-up was associated with a significantly
      lower rise in FPG at 3 yr. Urine N-telopeptide was not associated with any marker
      of metabolic phenotype. CONCLUSIONS: Serum osteocalcin concentration was
      inversely associated with blood markers of dysmetabolic phenotype and measures of
      adiposity. Our findings should be considered hypothesis generating, and they need
      to be replicated in human studies designed to test the hypothesis that
      osteocalcin affects metabolism.

PMID- 19088166
TI  - Clinical review: Drug-induced hypoglycemia: a systematic review.
AB  - CONTEXT: Drug-induced hypoglycemia is a significant adverse effect that may cause
      important morbidity. OBJECTIVE: The aim of the study was to systematically review
      the literature for drugs reported to cause hypoglycemia and assess the quality of
      evidence and strength of association supporting this causal link. DATA SOURCES:
      We searched electronic databases (MEDLINE, EMBASE, Web of Science, and SCOPUS)
      and the drug information system Micromedex through November 2007 and sought
      additional references from experts. STUDY SELECTION: Studies were eligible if
      they reported hypoglycemia as a side effect of a drug not used to treat
      hyperglycemia, regardless of their design, language, size, or follow-up duration.
      We excluded hypoglycemia caused by industrial exposures, nonpharmacological
      chemical exposures, alcohol, herbs, nutritional supplements, and in vitro and
      animal studies. DATA EXTRACTION: Reviewers extracted study characteristics and
      methodological quality and, when possible, data to estimate the odds of
      developing hypoglycemia when exposed to the offending agent. DATA SYNTHESIS: We
      found 448 eligible studies that described 2696 cases of hypoglycemia associated
      with 164 different drugs. The quality of evidence supporting associations between
      drugs and hypoglycemia was mostly very low due to methodological limitations and
      imprecision. The most commonly reported offending drugs were quinolones,
      pentamidine, quinine, beta blockers, angiotensin-converting enzyme agents, and
      IGF. CONCLUSIONS: Very low quality evidence substantiates the association between
      hypoglycemia and the use of numerous nondiabetic drugs.

PMID- 19088167
TI  - Clinical review: Hypoglycemia with intensive insulin therapy: a systematic review
      and meta-analyses of randomized trials of continuous subcutaneous insulin
      infusion versus multiple daily injections.
AB  - CONTEXT: Hypoglycemia limits the efficacy of intensive insulin therapy. The
      extent to which continuous insulin infusion (CSII) overcomes this limitation is
      unclear. OBJECTIVE: The aim was to summarize evidence on the effect of CSII and
      multiple daily injections (MDIs) on glycemic control and hypoglycemia. DATA
      SOURCES: We searched electronic databases between 2002 and March 2008. STUDY
      SELECTION: We selected published randomized trials of CSII vs. MDI. DATA
      EXTRACTION: Reviewers working in duplicate and independently extracted study
      characteristics and quality and differences in glycosylated hemoglobin (HbA1c)
      and hypoglycemic events. DATA SYNTHESIS: We found 15 eligible randomized trials
      of moderate quality, with elevated baseline and end-of-study HbA1c levels.
      Patients with type 1 diabetes using CSII had slightly lower HbA1c [random-effects
      weighted mean difference, -0.2%; 95% confidence interval (CI), -0.3, -0.1,
      compared with MDI], with no significant difference in severe (pooled odds ratio,
      0.48; 95% CI, 0.23, 1.00) or nocturnal hypoglycemia (pooled odds ratio 0.82, 95%
      CI 0.33, 2.03). Adolescents and adults with type 1 diabetes enrolled in crossover
      trials had nonsignificantly fewer minor hypoglycemia episodes per patient per
      week (-0.08; 95% CI, -0.21, 0.06) with CSII than MDI; children enrolled in
      parallel trials had significantly more episodes (0.68; 95% CI, 0.16, 1.20;
      P(interaction) = 0.03). Outcomes were not different in patients with type 2
      diabetes. CONCLUSIONS: Contemporary evidence indicates that compared to MDI, CSII
      slightly reduced HbA1c in adults with type 1 diabetes, with unclear impact on
      hypoglycemia. In type 2 diabetes, CSII and MDI had similar outcomes. The effect
      in patients with hypoglycemia unawareness or recurrent severe hypoglycemia
      remains unclear because of lack of data.

PMID- 19088168
TI  - Dipeptidyl-peptidase-IV inhibition augments postprandial lipid mobilization and
      oxidation in type 2 diabetic patients.
AB  - CONTEXT: Dipeptidyl-peptidase-IV (DPP-4) inhibition increases endogenous GLP-1
      activity, resulting in improved glycemic control in patients with type 2 diabetes
      mellitus. The metabolic response may be explained in part by extrapancreatic
      mechanisms. OBJECTIVE: We tested the hypothesis that DPP-4 inhibition with
      vildagliptin elicits changes in adipose tissue and skeletal muscle metabolism.
      DESIGN AND SETTING: We conducted a randomized, double-blind, crossover study at
      an academic clinical research center. PATIENTS: Twenty patients with type 2
      diabetes, body mass index between 28 and 40 kg/m(2), participated. INTERVENTION:
      INTERVENTION included 7 d treatment with the selective DPP-4 inhibitor
      vildagliptin or placebo and a standardized test meal on d 7. MAIN OUTCOME
      MEASURES: Venous DPP-4 activity, catecholamines, free fatty acids, glycerol,
      glucose, (pro)insulin, dialysate glucose, lactate, pyruvate, glycerol were
      measured. RESULTS: Fasting and postprandial venous insulin, glucose, glycerol,
      triglycerides, and free fatty acid concentrations were not different with
      vildagliptin and with placebo. Vildagliptin augmented the postprandial increase
      in plasma norepinephrine. Furthermore, vildagliptin increased dialysate glycerol
      and lactate concentrations in adipose tissue while suppressing dialysate lactate
      and pyruvate concentration in skeletal muscle. The respiratory quotient increased
      with meal ingestion but was consistently lower with vildagliptin. CONCLUSIONS:
      Our study is the first to suggest that DPP-4 inhibition augments postprandial
      lipid mobilization and oxidation. The response may be explained by sympathetic
      activation rather than a direct effect on metabolic status.

PMID- 19088169
TI  - Neo/adjuvant chemotherapy does not improve outcome in resected primary synovial
      sarcoma: a study of the French Sarcoma Group.
AB  - BACKGROUND: There are only scarce data about the benefit of adjunctive
      chemotherapy in patients with localized synovial sarcoma (SS). PATIENTS AND
      METHODS: Data from 237 SS patients recorded in the database of the French Sarcoma
      Group were retrospectively analyzed. The respective impact of radiotherapy, neo
      adjuvant chemotherapy and adjuvant chemotherapy on overall survival (OS), local
      recurrence-free survival (LRFS) and distant recurrence-free survival (DRFS) were
      assessed after adjustment to prognostic factors. RESULTS: The median follow-up
      was 58 months (range 1-321). Adjuvant, neo-adjuvant chemotherapy and
      postoperative radiotherapy were administered in 112, 45 and 181 cases,
      respectively. In all, 59% of patients treated with chemotherapy received an
      ifosfamide-containing regimen. The 5-year OS, LRFS and DRFS rates were 64.0%, 70%
      and 57%, respectively. On multivariate analysis, age >35 years old, grade 3 and
      not-R0 margins were highly significant independent predictors of worse OS. After
      adjustment to prognostic factors, radiotherapy significantly improved LRFS but
      not DRFS or OS. Neither neo-adjuvant nor adjuvant chemotherapy had significant
      impact on OS, LRFS or DRFS. CONCLUSION: As for other high-grade soft-tissue
      sarcomas, well-planned wide surgical excision with adjuvant radiotherapy remains
      the cornerstone of treatment for SS. Neo-adjuvant or adjuvant chemotherapy should
      not be delivered outside a clinical trial setting.

PMID- 19088171
TI  - An open-label study of vandetanib with pemetrexed in patients with previously
      treated non-small-cell lung cancer.
AB  - BACKGROUND: Vandetanib (ZACTIMA; ZD6474) is a once-daily, oral inhibitor of
      vascular endothelial growth factor receptor and epidermal growth factor receptor
      signaling. The safety and tolerability of vandetanib plus pemetrexed was assessed
      in patients with advanced non-small-cell lung cancer (NSCLC). PATIENTS AND
      METHODS: Patients with previously treated NSCLC (stage IIIB/IV) received once
      daily oral vandetanib (100 or 300 mg) with pemetrexed (500 mg/m(2) i.v. infusion
      every 21 days). RESULTS: Patients received vandetanib 100 mg + pemetrexed (n=10)
      or vandetanib 300 mg + pemetrexed (n=11). The protocol definition of a tolerable
      dose [vandetanib-related dose-limiting toxicity (DLT) in less than 2 patients]
      was met in both dose cohorts, with one DLT reported in each: asymptomatic QTc
      prolongation (>100 ms increase from baseline, but absolute QTc<500 ms) in the 100
      mg cohort and interstitial lung disease, which resolved after steroid therapy, in
      the 300 mg cohort. The most common adverse events were rash, anorexia, fatigue
      and diarrhea (all n=10). CONCLUSION: Vandetanib and pemetrexed in combination
      were generally well tolerated in patients with advanced NSCLC.

PMID- 19088170
TI  - Angiogenesis and antiangiogenic therapy in non-Hodgkin's lymphoma.
AB  - Angiogenesis, the growth of new blood vessels, requires dynamic expansion,
      assembly and stabilization of vascular endothelial cells in response to
      proangiogenic stimuli. Antiangiogenic strategies have become an important
      therapeutic modality for solid tumors. While many aspects of postnatal
      pathological angiogenesis have been extensively studied in the context of
      nonhematopoietic neoplasms, the precise role of these processes in lymphoma
      pathogenesis is under active investigation. Lymphoma growth and progression is
      potentiated by at least two distinct angiogenic mechanisms: autocrine stimulation
      of tumor cells via expression of vascular endothelial growth factor (VEGF) and
      VEGF receptors by lymphoma cells, as well as paracrine influences of
      proangiogenic tumor microenvironment on both local neovascular transformation and
      recruitment of circulating bone marrow-derived progenitors. Lymphoma-associated
      infiltrating host cells including hematopoietic monocytes, T cells and
      mesenchymal pericytes have increasingly been associated with the pathogenesis and
      prognosis of lymphoma, in part providing perivascular guidance and support to
      neoangiogenesis. Collectively, these distinct angiogenic mechanisms appear to be
      important therapeutic targets in selected non-Hodgkin's lymphoma (NHL) subtypes.
      Understanding these pathways has led to the introduction of antiangiogenic
      treatment strategies into the clinic where they are currently under assessment in
      several ongoing studies of NHL patients.

PMID- 19088172
TI  - Comparison of epidermal growth factor receptor mutations between primary and
      corresponding metastatic tumors in tyrosine kinase inhibitor-naive non-small-cell
      lung cancer.
AB  - BACKGROUND: Mutations of the epidermal growth factor receptor (EGFR) gene in non
      small-cell lung cancer (NSCLC) patients predict the patients who will respond to
      EGFR tyrosine kinase inhibitor (TKI) treatment. A recent study has suggested that
      33% of NSCLC showed primary tumor/metastasis discordance of EGFR expression by
      immunohistochemistry analysis. We intended to find out whether the EGFR mutations
      of primary lung cancers are concordant to that of corresponding metastatic
      tumors. MATERIALS AND METHODS: We analyzed EGFR exons 18-21 from paired primary
      and metastatic tumors in 67 lung cancer patients who had not received TKI before
      tissues were sampled. RESULTS: Using the direct sequencing method, 9 of 18 (50%)
      patients with EGFR mutation-positive primary lung tumors had lost the mutations
      in metastases. For 26 patients who were EGFR mutation positive in the metastatic
      tumors, 17 (65%) were negative in the primary tumors. We analyzed these paired
      tissues with discrepant EGFR mutations by the Scorpion Amplified Refractory
      Mutation System assay. Finally, the discordant rate reached 27% (18 of 67 cases).
      CONCLUSION: EGFR mutations in primary lung tumors do not always reflect the same
      situation in metastases. Analysis of EGFR mutations in the primary lung tumor
      would be inadequate for planning the use of TKI for advanced NSCLC.

PMID- 19088173
TI  - The recent decline in mortality from Hodgkin lymphomas in central and eastern
      Europe.
AB  - BACKGROUND: Hodgkin lymphoma (HL) is a largely curable disease and its mortality
      had steadily declined in western Europe since the late 1960s. Only modest
      declines were, however, observed in central/eastern Europe. MATERIALS AND
      METHODS: We updated trends in mortality from HL in various European areas up to
      2004 and analyzed patterns in incidence for selected European countries providing
      national data. RESULTS: In most western European countries, HL mortality
      continued to steadily decline up to the mid 2000s. More recent reductions were
      also observed in eastern European countries. Overall, mortality from HL declined
      from 1.17/100,000 (age-standardized, world population) in 1980-1989 to
      1.42/100,000 in 2000-2004 in men from the 15 member states of the European Union
      (EU) from western and northern Europe. In the EU 10 accession countries of
      central and eastern Europe, male mortality from HL was 1.42/100,000 in 1980-1984,
      1.32 in 1990-1994, and declined to 0.76 in 2000-2004. Similar trends were
      observed in women. No consistent patterns were found for HL incidence.
      CONCLUSIONS: The present work confirms the persistent declines in HL mortality in
      western European countries, and shows favorable patterns over more recent
      calendar years in central/eastern ones, where rates, however, are still at levels
      observed in western Europe in the early 1990s.

PMID- 19088175
TI  - Age-related enlargement of lymphoid tissue and altered leukocyte composition in
      serglycin-deficient mice.
AB  - Serglycin (SG) is a proteoglycan that is located predominantly in the secretory
      granules of hematopoietic cells. Previous studies have established a crucial role
      for SG in promoting the storage of various secretory granule compounds that are
      of importance in the immune defense system. Here, we show that mice lacking SG
      spontaneously develop enlargement of multiple lymphoid organs, including the
      spleen, Peyer's patches (PP), and bronchus-associated lymphoid tissue. In the
      spleen, the lack of SG resulted in a significant decrease in the proportion of
      CD4(+) cells as well as an increase of the CD45RC(+) leukocyte population,
      indicating an expansion of naive lymphocytes. In the PP, the lack of SG resulted
      in a general increase in cellularity, without significant alterations in the
      proportion of individual leukocyte populations. The enlargement of lymphoid
      tissues was not accompanied by increased serum levels of inflammatory cytokines.
      The number of mast cells in the peritoneum was not affected by the lack of SG, as
      judged by surface staining for CD117 (c-kit). However, the intensity of c-kit
      staining was reduced significantly in SG null animals. Moreover, the number of
      peritoneal macrophages, defined by morphological criteria and by CD11b staining,
      was decreased markedly in older, SG-deficient animals. Finally, experiments in
      which airway inflammation was induced by bacterial LPS revealed a more pronounced
      inflammatory response in old, SG-deficient as compared with wild-type mice. Taken
      together, our data show that SG deficiency causes multiple, age-related effects
      on the lymphoid system.

PMID- 19088174
TI  - The role of the membrane cytoskeleton cross-linker ezrin in medulloblastoma
      cells.
AB  - Medulloblastoma is a highly malignant brain tumor that occurs predominantly in
      children. The molecular pathogenesis of medulloblastoma is under investigation.
      Previously, we used complementary DNA microarray analysis to compare patterns of
      gene expression in medulloblastoma samples versus normal cerebellum. The
      cytoskeletal protein ezrin was found to be overexpressed in medulloblastoma
      compared with normal cerebellum, an observation that was further validated by
      immunohistochemistry and real-time PCR analysis. To assess the role of ezrin in
      medulloblastoma, we studied ezrin's role in medulloblastoma migration, invasion,
      and adhesion. Western blotting and immunofluorescence showed high expression of
      ezrin in four medulloblastoma cell lines, and ezrin was primarily localized to
      filopodia. Ezrin-specific small interfering RNA suppressed the formation of
      filopodia and in vitro migration, invasion, and adhesion. We also used a stably
      transfected medulloblastoma cell line to study the effect of ezrin
      overexpression. We showed that high expression of ezrin promotes filopodia
      formation and in vitro invasion. Finally, athymic mice implanted with ezrin
      overexpressing DAOY medullo-blastoma cell clones in the cerebellum showed
      shortened survival compared with controls. These findings suggest that, in
      addition to other cytoskeletal proteins, ezrin plays an important role in
      medulloblastoma adhesion, migration, and invasion.

PMID- 19088176
TI  - Dermatan sulfate proteoglycan biglycan as a potential selectin L/CD44 ligand
      involved in selective recruitment of peripheral blood CD16(-) natural killer
      cells into human endometrium.
AB  - Unique CD16(-) NK cells acutely increase in the human uterine endometrium after
      ovulation. The origin of these NK cells remains unknown, but they may be
      recruited selectively from the circulation. Proteoglycans and their
      glycosaminoglycan side-chains expressed on endometrial microvascular endothelial
      cells play a key role in lymphocyte tethering/rolling, the initial step of
      lymphocyte extravasation. In this study, we sought for the potential
      proteoglycans involved in tethering/rolling of peripheral blood CD16(-) NK cells
      on endometrial microvascular endothelial cells. As compared with CD16(+) NK cells
      and non-NK cells, enriched peripheral blood CD16(-) NK cells bound preferably to
      immobilized glycosaminoglycans except for keratan sulfate. CD16(-) NK cells bound
      maximally to dermatan sulfate (DS), which was diminished by enzymatic
      pretreatment with dermatanase and chondroitinase ABC, but not with chondroitinase
      ACII. The binding capacity of CD16(-) NK cells to DS was attenuated by blocking
      antibodies against selectin L and CD44 or pretreatment of CD16(-) NK cells with
      IL-15. Of three known DS proteoglycans, biglycan and decorin but not epiphycan
      were expressed in the human cycling endometrium. In the endometrial microvessels,
      the immunoreactivity for biglycan was greater in the secretory phase than in the
      proliferative phase, and there was little, if any, immunoreactivity for decorin
      throughout the menstrual cycle. The ovarian steroid progesterone enhanced
      biglycan expression in cultured human uterine microvascular endothelial cells.
      These findings demonstrated that DS proteoglycan biglycan is a potential selectin
      L/CD44 ligand involved in tethering/rolling of peripheral blood CD16(-) NK cells
      on endometrial microvascular endothelial cells.

PMID- 19088178
TI  - Leukocyte trafficking in primary immunodeficiencies.
AB  - Leukocyte recirculation through central and peripheral lymphoid organs and
      peripheral tissues is essential to maintain immune homeostasis. Some of the
      genetically determined, primary immunodeficiencies compromise leukocyte
      trafficking. Here, we review the mechanisms and consequences of impaired
      leukocyte trafficking in leukocyte adhesion-deficiency syndromes, Warts-Hypo
      gamma-globulinemia-Infections-Myelokathexis syndrome and Wiskott-Aldrich
      syndrome.

PMID- 19088177
TI  - Differential lymphopenia-induced homeostatic proliferation for CD4+ and CD8+ T
      cells following septic injury.
AB  - Sepsis is a severe, life-threatening infection and a leading cause of death in
      hospitals. A hallmark of sepsis is the profound apoptosis-induced depletion of
      lymphocytes generating a lymphopenic environment. As lymphopenia can induce
      nonantigen-driven homeostatic proliferation (HP), we examined this process during
      sepsis. CD4(+) and CD8(+) T cells, which were depleted within 24 h of sepsis
      induction, remained at significantly reduced levels until Day 21 when normal
      numbers were detected. When HP was examined, naive CD8(+) T cells proliferated
      between Day 7 and Day 21 post-cecal ligation and puncture, developing into memory
      cells with relatively few cells expressing an activation phenotype. Conversely,
      naive CD4(+) T cells did not undergo HP, but proportionally higher numbers
      expressed activation markers. Adoptive transfer studies revealed that T cells
      from mice that had recovered from sepsis were not protective when transferred to
      naive mice undergoing sepsis. In addition, the TCR repertoire was not skewed
      toward any specific Vbeta type but resembled the repertoire found in normal mice,
      suggesting that T cells were not primed to antigens resulting from the infection.
      Interestingly, depletion of endogenous CD8(+) but not CD4(+) T cells restored the
      ability of naive CD4(+) T cells to undergo HP, increasing the number of CD4(+) T
      cells with memory but not activation markers. We conclude that homeostatic
      control in the postseptic environment permits recovery of the T cell repertoire
      to normal levels without generating antigen-specific memory or aberrant T cell
      specificities. Restoration of homeostatic control mechanisms might be a rational
      therapy for this disorder.

PMID- 19088179
TI  - Neutrophil elastase activity compensates for a genetic lack of matrix
      metalloproteinase-9 (MMP-9) in leukocyte infiltration in a model of experimental
      peritonitis.
AB  - Extracellular proteolysis of basement membranes and matrix is required for
      leukocyte diapedesis and migration to the inflammatory focus. Neutrophil elastase
      (NE) and matrix metalloproteinases (MMPs) are among the enzymes involved in these
      processes, as shown in mice genetically deprived of such enzymes. However,
      studies with MMP-9(-/-) mice revealed that albeit neutrophil influx is impaired
      initially in these animals versus controls, neutrophilia is subsequently
      augmented during later stages of zymosan peritonitis. MMP-9 as a MMP and NE as a
      serine protease belong to different enzyme classes. As MMP-9 and NE are produced
      by neutrophils and have similar biological effects on matrix remodeling, it was
      evaluated whether enhanced NE activity might compensate for the lack of MMP-9. In
      genetically uncompromised mice, two waves of NE expression and activity during
      zymosan peritonitis were observed in inflammatory neutrophils and macrophages at
      the time of influx of the respective cell populations into the peritoneum.
      Additionally, NE expression was associated with the activity of resident
      peritoneal mast cells and macrophages, as their depletion reduced NE activity.
      Most importantly, the NE mRNA and protein expression and activity were enhanced
      significantly in MMP-9(-/-) mice during late stages of zymosan peritonitis. In
      addition, the application of a selective NE inhibitor restrained enhanced
      neutrophil accumulation significantly. In conclusion, during acute peritoneal
      inflammation, NE expression and activity increase gradually, facilitating
      leukocyte influx. Moreover, increased NE activity might compensate for a genetic
      lack of MMP-9 (as detected in MMP-9(-/-) mice), resulting in delayed accumulation
      of neutrophils during late zymosan peritonitis.

PMID- 19088180
TI  - Embryonic caffeine exposure induces adverse effects in adulthood.
AB  - The purpose of this study was to determine both the short-term effects on cardiac
      development and embryo growth and the long-term effects on cardiac function and
      body composition of in utero caffeine exposure. Pregnant mice (C57BL/6) were
      exposed to hypoxia (10% O(2)) or room air from embryonic days (E) 8.5-10.5, and
      treated with caffeine (20 mg/kg, i.p.) or vehicle (normal saline, 0.9% NaCl).
      This caffeine dose results in a circulating level that is equivalent to 2 cups of
      coffee in humans. Hypoxic exposure acutely reduced embryonic growth by 30%.
      Exposure to a single dose of caffeine inhibited cardiac ventricular development
      by 53% in hypoxia and 37% in room air. Caffeine exposure resulted in inhibition
      of hypoxia-induced HIF1alpha protein expression in embryos by 40%. When offspring
      from dams treated with a single dose of caffeine were studied in adulthood, we
      observed that caffeine treatment alone resulted in a decrease in cardiac function
      of 38%, as assessed by echocardiography. We also observed a 20% increase in body
      fat with male mice exposed to caffeine. Caffeine was dissolved in normal saline,
      so it was used as a control. Room air controls were used to compare to the
      hypoxic mice. Exposure to a single dose of caffeine during embryogenesis results
      in both short-term effects on cardiac development and long-term effects on
      cardiac function.

PMID- 19088181
TI  - Macrophage migration inhibitory factor is critical to interleukin-5-driven
      eosinophilopoiesis and tissue eosinophilia triggered by Schistosoma mansoni
      infection.
AB  - Macrophage migration inhibitory factor (MIF) participates in the pathogenesis of
      inflammatory diseases, including asthma, in which it enhances airway
      hypersensitivity and tissue eosinophilia. Herein, we investigated the role of MIF
      in eosinophilopoiesis and tissue eosinophilia using Schistosoma mansoni
      infection. MIF-deficient (Mif(-/-)) mice had similar numbers of adult worms,
      eggs, and granulomas compared to wild-type mice, but the size of granulomas was
      strikingly reduced due to smaller numbers of eosinophils. MIF did not affect the
      acquired response to infection, as Mif(-/-) mice produced normal amounts of Th2
      cytokines and IgE. Nevertheless, recombinant MIF (rMIF) behaved as a
      chemoattractant for eosinophils, what could partially explain the reduced
      eosinophilia in infected Mif(-/-) mice. Moreover, the percentage of eosinophils
      was reduced in bone marrows of Mif(-/-) mice chronically infected with S. mansoni
      compared to wild type. Mif(-/-) had impaired eosinophilopoiesis in response to
      interleukin (IL)-5 and addition of rMIF to bone marrow cultures from IL-5
      transgenic mice enhanced the generation of eosinophils. In the absence of MIF,
      eosinophil precursors were unable to survive the IL-5-supplemented cell culture,
      and were ingested by macrophages. Treatment with pancaspase inhibitor z-VAD or
      rMIF promoted the survival of eosinophil progenitors. Together, these results
      indicate that MIF participates in IL-5-driven maturation of eosinophils and in
      tissue eosinophilia associated with S. mansoni infection.

PMID- 19088182
TI  - Structural and functional characterization of two genetically related meucin
      peptides highlights evolutionary divergence and convergence in antimicrobial
      peptides.
AB  - Both vertebrates and invertebrates employ alpha-helical antimicrobial peptides
      (AMPs) as an essential component of their innate immune system. However,
      evolutionary relation of these immune molecules remains unresolved. Venoms, as
      key weapons of venomous arthropods for prey and defense, receive increasing
      recognition as an emerging source of such peptides. From a cDNA library prepared
      from the venom gland of the scorpion Mesobuthus eupeus, clones encoding
      precursors of two new AMPs, named meucin-13 (IFGAIAGLLKNIF-NH(2)) and meucin-18
      (FFGHLFKLATKIIPSLFQ), have been isolated. The precursor of meucins consists of a
      signal peptide, a mature peptide, and an acidic propeptide, in which dibasic
      residues as the typical processing signal are located between the mature and
      propeptide. Meucin-13 is an ortholog of several previously described AMPs from
      scorpion venom and has also detectable sequence similarity to temporins, a large
      family of AMPs from frog skin, whereas meucin-18 displays some similarity to AMPs
      from diverse origin including arthropod venoms, fish mast cells, and frog skins.
      These two meucin peptides form alpha-helical structure in the presence of 50%
      trifluoroethanol (TFE), a membrane-mimicking environment, as identified by
      circular dichroism (CD) spectroscopy. This finding is further verified by their
      NMR structures that show a typical alpha-helical amphipathic design, a structural
      prerequisite for cytolytic activity. Meucins exhibit extensive cytolytic effects
      on both prokaryotic and eukaryotic cells (gram(+) and gram(-) bacteria, fungi,
      yeasts, rabbit erythrocytes, and rat dorsal root ganglion cells) at micromolar
      concentrations. It is remarkable that muecin-18 was 2- to >14-fold more potent
      than meucin-13 against nearly all the cells tested. Structural differences in
      hydrophilic/hydrophobic balance and cationic amino acid location between two
      meucins could account for their differential potency. Despite these differences,
      commonalities at precursor organization, three-dimensional structure, and
      biological function suggests that meucins are two evolutionarily related AMPs and
      likely originated from a common ancestor by gene duplication. Our work presented
      here also provides new insights into an evolutionary link among AMPs from
      invertebrates and vertebrates and clues for evolutionary convergence between AMPs
      and virus fusion domains.

PMID- 19088183
TI  - Mitochondrial dysfunction in mut methylmalonic acidemia.
AB  - Methylmalonic acidemia is an autosomal recessive inborn error of metabolism
      caused by defective activity of methylmalonyl-CoA mutase (MUT) that exhibits
      multiorgan system pathology. To examine whether mitochondrial dysfunction is a
      feature of this organic acidemia, a background-modified Mut-knockout mouse model
      was constructed and used to examine mitochondrial ultrastructure and respiratory
      chain function in the tissues that manifest pathology in humans. In parallel, the
      liver from a patient with mut methylmalonic acidemia was studied in a similar
      fashion. Megamitochondria formed early in life in the hepatocytes of the Mut(-/-)
      animals and progressively enlarged. Liver extracts prepared from the mutants at
      multiple time points displayed respiratory chain dysfunction, with diminished
      cytochrome c oxidase activity and reduced intracellular glutathione compared to
      control littermates. Over time, the exocrine pancreas and proximal tubules of the
      kidney also exhibited megamitochondria, and older mutant mice eventually
      developed tubulointerstitial renal disease. The patient liver displayed similar
      morphological and enzymatic findings as observed in the murine tissues. These
      murine and human studies establish that megamitochondria formation with
      respiratory chain dysfunction occur in a tissue-specific fashion in methylmalonic
      acidemia and suggest treatment approaches based on improving mitochondrial
      function and ameliorating the effects of oxidative stress.

PMID- 19088184
TI  - The clinical value of [18F]fluoro-dihydroxyphenylalanine positron emission
      tomography in primary diagnosis, staging, and restaging of neuroendocrine tumors.
AB  - The study was set up to determine the clinical value of dihydroxyphenylalanine
      positron emission tomography-computed tomography ([(18)F]DOPA PET-CT) in patients
      with neuroendocrine tumors (NETs). Eighty-two patients with suspected/known NET
      were imaged with PET(-CT) using [(18)F]DOPA. Patients were divided into two
      groups: primary diagnosis/staging and restaging of disease. All patients without
      previous diagnosis of NET had biochemical proof of disease. The diagnostic
      accuracy of PET was assessed by comparing the histopathology and clinical follow
      up. The overall accuracy of [(18)F]DOPA PET was 90%. In patients having PET for
      primary diagnosis/staging (n=32), the accuracy of PET was 88%, and for restaging
      92% (n=61). The mean s.d. sizes of primary and metastatic lesions detected by PET
      were 26+/-11 and 16+/-9 mm respectively. In organ-region-specific analysis, the
      sensitivity and specificity were 100% in the primary diagnosis of
      pheochromocytoma (n=16) and metastases were found in all cases with recurrent
      disease (n=5). The accuracy for NET of gastrointestinal tract was 92% in
      restaging (n=24). For the NETs located in the head-neck-thoracic region (n=19),
      the overall accuracy of PET was 89% including 12 cases of recurrent medullary
      thyroid cancer with a sensitivity of 90%. In analysis of patients with
      biochemical proof of disease combined with negative conventional imaging methods,
      PET had positive and negative predictive value of 92% and 95% respectively.
      [(18)F]DOPA PET-CT provided important additional information in the diagnosis of
      pheochromocytoma and restaging of known NET. Both in primary diagnosis and in
      patients with formerly known NET and increasing tumor markers, [(18)F]DOPA PET-CT
      is a sensitive first-line imaging method.

PMID- 19088185
TI  - Gibraltar data are too sparse to inform on Neanderthal exploitation of coastal
      resources.

PMID- 19088186
TI  - Unrealistic assumptions invalidate extinction estimates.

PMID- 19088187
TI  - Genome-wide analysis of cancer/testis gene expression.
AB  - Cancer/Testis (CT) genes, normally expressed in germ line cells but also
      activated in a wide range of cancer types, often encode antigens that are
      immunogenic in cancer patients, and present potential for use as biomarkers and
      targets for immunotherapy. Using multiple in silico gene expression analysis
      technologies, including twice the number of expressed sequence tags used in
      previous studies, we have performed a comprehensive genome-wide survey of
      expression for a set of 153 previously described CT genes in normal and cancer
      expression libraries. We find that although they are generally highly expressed
      in testis, these genes exhibit heterogeneous gene expression profiles, allowing
      their classification into testis-restricted (39), testis/brain-restricted (14),
      and a testis-selective (85) group of genes that show additional expression in
      somatic tissues. The chromosomal distribution of these genes confirmed the
      previously observed dominance of X chromosome location, with CT-X genes being
      significantly more testis-restricted than non-X CT. Applying this core
      classification in a genome-wide survey we identified >30 CT candidate genes; 3 of
      them, PEPP-2, OTOA, and AKAP4, were confirmed as testis-restricted or testis
      selective using RT-PCR, with variable expression frequencies observed in a panel
      of cancer cell lines. Our classification provides an objective ranking for
      potential CT genes, which is useful in guiding further identification and
      characterization of these potentially important diagnostic and therapeutic
      targets.

PMID- 19088188
TI  - Structural origins for the product specificity of SET domain protein
      methyltransferases.
AB  - SET domain protein lysine methyltransferases (PKMTs) regulate transcription and
      other cellular functions through site-specific methylation of histones and other
      substrates. PKMTs catalyze the formation of monomethylated, dimethylated, or
      trimethylated products, establishing an additional hierarchy with respect to
      methyllysine recognition in signaling. Biochemical studies of PKMTs have
      identified a conserved position within their active sites, the Phe/Tyr switch,
      that governs their respective product specificities. To elucidate the mechanism
      underlying this switch, we have characterized a Phe/Tyr switch mutant of the
      histone H4 Lys-20 (H4K20) methyltransferase SET8, which alters its specificity
      from a monomethyltransferase to a dimethyltransferase. The crystal structures of
      the SET8 Y334F mutant bound to histone H4 peptides bearing unmodified,
      monomethyl, and dimethyl Lys-20 reveal that the phenylalanine substitution
      attenuates hydrogen bonding to a structurally conserved water molecule adjacent
      to the Phe/Tyr switch, facilitating its dissociation. The additional space
      generated by the solvent's dissociation enables the monomethyllysyl side chain to
      adopt a conformation that is catalytically competent for dimethylation and
      furnishes sufficient volume to accommodate the dimethyl epsilon-ammonium product.
      Collectively, these results indicate that the Phe/Tyr switch regulates product
      specificity through altering the affinity of an active-site water molecule whose
      dissociation is required for lysine multiple methylation.

PMID- 19088189
TI  - Regulation of lymphocyte progenitor survival by the proapoptotic activities of
      Bim and Bid.
AB  - On their entry into the thymus, developing lymphocyte progenitors depend on
      signaling from the pre-T cell receptor (pre-TCR), which orchestrates
      differentiation, cell proliferation, and survival. The exact mechanism of pre-TCR
      mediated suppression of T cell death remains unclear and controversial. Here, we
      identify Bim and Bid, 2 members of the BH3-only group of the BCL2 family, as
      important regulators of pre-T cell death. Both factors are highly expressed in
      proapoptotic thymocytes and their expression is suppressed on signaling through
      the pre-TCR. Their expression is directly regulated by the transcription factors
      FoxO3a and p53. Bid expression and p53 activity are related to the ongoing
      rearrangement of the TCR loci and induced DNA damage responses. Bim expression
      and FoxO3a nuclear translocation are directly controlled by the pre-TCR by means
      of its downstream kinase Akt/PKB. Interestingly, deletion of either gene on a pre
      TCR(-/-) background rescues survival, but fails to induce further progenitor
      differentiation uncoupling the 2 processes.

PMID- 19088190
TI  - Visualization of IFNbeta production by plasmacytoid versus conventional dendritic
      cells under specific stimulation conditions in vivo.
AB  - Type I interferons, a protein family of multiple IFNalphas and a single IFNbeta,
      initially identified on the basis of their antiviral activities have recently
      been attributed important roles in bacterial and parasitic infections. To assess
      the cellular sources of IFNbeta, the IFN produced first in most situations, we
      created an IFNbeta reporter-knockin mouse, in which yellow fluorescent protein
      (YFP) is expressed from a bicistronic mRNA linked by an internal ribosomal entry
      site to the endogenous IFNbeta mRNA. This YFP expression allows spatiotemporal
      tracking of the initiation of the type I IFN response on a single-cell level. In
      vitro bone marrow-derived macrophages (BMMPhis) and bone marrow-derived dendritic
      cells (BMDCs) show IFNbeta production from distinct cell subpopulations in
      response to defined pathogen compounds. A subpopulation of GMCSF-derived BMDCs
      produced IFNbeta after poly(I:C), 3'5'-cytidylylguanosine (CpG), or LPS
      treatment, whereas Flt3-L-cultured plasmacytoid DCs (pDCs) responded mainly to
      CpG. After poly(I:C) injection in vivo, IFNbeta-producing cells localize to the
      splenic marginal zone and the lymph node subcapsular sinus. Infection with murine
      cytomegalovirus (MCMV) induces IFNbeta/YFP expression exclusively in few
      activated pDCs at the T cell/B cell interface of the splenic white pulp. This
      IFNbeta/YFP reporter mouse represents a reliable tool for the visualization and
      characterization of IFNbeta-producing cells in vitro and in vivo.

PMID- 19088191
TI  - miR-519 reduces cell proliferation by lowering RNA-binding protein HuR levels.
AB  - Gene expression is potently regulated through the action of RNA-binding proteins
      (RBPs) and microRNAs (miRNAs). Here, we present evidence of a miRNA regulating an
      RBP. The RBP HuR can stabilize and modulate the translation of numerous target
      mRNAs involved in cell proliferation, but little is known about the mechanisms
      that regulate HuR abundance. We identified two putative sites of miR-519
      interaction on the HuR mRNA, one in its coding region (CR), one in its 3'
      untranslated region (UTR). In several human carcinoma cell lines tested, HeLa
      (cervical), HCT116 and RKO (colon), and A2780 (ovarian), overexpression of a miR
      519 precursor [(Pre)miR-519] reduced HuR abundance, while inhibiting miR-519 by
      using an antisense RNA [(AS)miR-519] elevated HuR levels. The influence of miR
      519 was recapitulated using heterologous reporter constructs that revealed a
      greater repressive effect on the HuR CR than the HuR 3'-UTR target sequences. miR
      519 did not alter HuR mRNA abundance, but reduced HuR biosynthesis, as determined
      by measuring nascent HuR translation and HuR mRNA association with polysomes.
      Modulation of miR-519 leading to altered HuR levels in turn affected the levels
      of proteins encoded by HuR target mRNAs. In keeping with HuR's proliferative
      influence, (AS)miR-519 significantly increased cell number and [(3)H]-thymidine
      incorporation, while (Pre)miR-519 reduced these parameters. Importantly, the
      growth-promoting effects of (AS)miR-519 required the presence of HuR, because
      downregulation of HuR by RNAi dramatically suppressed its proliferative action.
      In sum, miR-519 represses HuR translation, in turn reducing HuR-regulated gene
      expression and cell division.

PMID- 19088192
TI  - Growth hormone-releasing hormone as an agonist of the ghrelin receptor GHS-R1a.
AB  - Ghrelin synergizes with growth hormone-releasing hormone (GHRH) to potentiate
      growth hormone (GH) response through a mechanism not yet fully characterized.
      This study was conducted to analyze the role of GHRH as a potential ligand of the
      ghrelin receptor, GHS-R1a. The results show that hGHRH(1-29)NH(2) (GHRH) induces
      a dose-dependent calcium mobilization in HEK 293 cells stably transfected with
      GHS-R1a an effect not observed in wild-type HEK 293 cells. This calcium rise is
      also observed using the GHRH receptor agonists JI-34 and JI-36. Radioligand
      binding and cross-linking studies revealed that calcium response to GHRH is
      mediated by the ghrelin receptor GHS-R1a. GHRH activates the signaling route of
      inositol phosphate and potentiates the maximal response to ghrelin measured in
      inositol phosphate turnover. The presence of GHRH increases the binding capacity
      of (125)I-ghrelin in a dose dependent-fashion showing a positive binding
      cooperativity. In addition, confocal microscopy in CHO cells transfected with GHS
      R1a tagged with enhanced green fluorescent protein shows that GHRH activates the
      GHS-R1a endocytosis. Furthermore, the selective GHRH-R antagonists, JV-1-42 and
      JMR-132, act also as antagonists of the ghrelin receptor GHS-R1a. Our findings
      suggest that GHRH interacts with ghrelin receptor GHS-R1a, and, in consequence,
      modifies the ghrelin-associated intracellular signaling pathway. This interaction
      may represent a form of regulation, which could play a putative role in the
      physiology of GH regulation and appetite control.

PMID- 19088193
TI  - Multilayer three-dimensional super resolution imaging of thick biological
      samples.
AB  - Recent advances in optical microscopy have enabled biological imaging beyond the
      diffraction limit at nanometer resolution. A general feature of most of the
      techniques based on photoactivated localization microscopy (PALM) or stochastic
      optical reconstruction microscopy (STORM) has been the use of thin biological
      samples in combination with total internal reflection, thus limiting the imaging
      depth to a fraction of an optical wavelength. However, to study whole cells or
      organelles that are typically up to 15 microm deep into the cell, the extension
      of these methods to a three-dimensional (3D) super resolution technique is
      required. Here, we report an advance in optical microscopy that enables imaging
      of protein distributions in cells with a lateral localization precision better
      than 50 nm at multiple imaging planes deep in biological samples. The approach is
      based on combining the lateral super resolution provided by PALM with two-photon
      temporal focusing that provides optical sectioning. We have generated super
      resolution images over an axial range of approximately 10 microm in both
      mitochondrially labeled fixed cells, and in the membranes of living S2 Drosophila
      cells.

PMID- 19088194
TI  - Determination of tag density required for digital transcriptome analysis:
      application to an androgen-sensitive prostate cancer model.
AB  - High-throughput sequencing has rapidly gained popularity for transcriptome
      analysis in mammalian cells because of its ability to generate digital and
      quantitative information on annotated genes and to detect transcripts and mRNA
      isoforms. Here, we described a double-random priming method for deep sequencing
      to profile double poly(A)-selected RNA from LNCaP cells before and after androgen
      stimulation. From approximately 20 million sequence tags, we uncovered 71% of
      annotated genes and identified hormone-regulated gene expression events that are
      highly correlated with quantitative real time PCR measurement. A fraction of the
      sequence tags were mapped to constitutive and alternative splicing events to
      detect known and new mRNA isoforms expressed in the cell. Finally, curve fitting
      was used to estimate the number of tags necessary to reach a "saturating"
      discovery rate among individual applications. This study provides a general guide
      for analysis of gene expression and alternative splicing by deep sequencing.

PMID- 19088195
TI  - Antagonism of E2F-1 regulated Bnip3 transcription by NF-kappaB is essential for
      basal cell survival.
AB  - The transcription factor E2F-1 drives proliferation and death, but the mechanisms
      that differentially regulate these divergent actions are poorly understood. The
      hypoxia-inducible death factor Bnip3 is an E2F-1 target gene and integral
      component of the intrinsic mitochondrial death pathway. The mechanisms that
      govern Bnip3 gene activity remain cryptic. Herein we show that the transcription
      factor NF-kappaB provides a molecular switch that determines whether E2F-1
      signals proliferation or death under physiological conditions. We show under
      basal nonapoptotic conditions that NF-kappaB constitutively occupies and
      transcriptionally silences Bnip3 gene transcription by competing with E2F-1 for
      Bnip3 promoter binding. Conversely, in the absence of NF-kappaB, or during
      hypoxia when NF-kappaB abundance is reduced, basal Bnip3 gene transcription is
      activated by the unrestricted binding of E2F-1 to the Bnip3 promoter. Genetic
      knock-down of E2F-1 or retinoblastoma gene product over-expression in cardiac and
      human pancreatic cancer cells deficient for NF-kappaB signaling abrogated basal
      and hypoxia-inducible Bnip3 transcription. The survival kinase PI3K/Akt inhibited
      Bnip3 expression levels in cells in a manner dependent upon NF-kappaB activation.
      Hence, by way of example, we show that the transcriptional inhibition of E2F-1
      dependent Bnip3 expression by NF-kappaB highlights a survival pathway that
      overrides the E2F-1 tumor suppressor program. Our data may explain more
      fundamentally how cells, by selectively inhibiting E2F-1-dependent death gene
      transcription, avert apoptosis down-stream of the retinoblastoma/E2F-1 cell cycle
      pathway.

PMID- 19088196
TI  - DEAD-box proteins can completely separate an RNA duplex using a single ATP.
AB  - DEAD-box proteins are ubiquitous in RNA metabolism and use ATP to mediate RNA
      conformational changes. These proteins have been suggested to use a fundamentally
      different mechanism from the related DNA and RNA helicases, generating local
      strand separation while remaining tethered through additional interactions with
      structured RNAs and RNA-protein (RNP) complexes. Here, we provide a critical test
      of this model by measuring the number of ATP molecules hydrolyzed by DEAD-box
      proteins as they separate short RNA helices characteristic of structured RNAs (6
      11 bp). We show that the DEAD-box protein CYT-19 can achieve complete strand
      separation using a single ATP, and that 2 related proteins, Mss116p and Ded1p,
      display similar behavior. Under some conditions, considerably <1 ATP is
      hydrolyzed per separation event, even though strand separation is strongly
      dependent on ATP and is not supported by the nucleotide analog AMP-PNP. Thus, ATP
      strongly enhances strand separation activity even without being hydrolyzed, most
      likely by eliciting or stabilizing a protein conformation that promotes strand
      separation, and AMP-PNP does not mimic ATP in this regard. Together, our results
      show that DEAD-box proteins can disrupt short duplexes by using a single cycle of
      ATP-dependent conformational changes, strongly supporting and extending models in
      which DEAD-box proteins perform local rearrangements while remaining tethered to
      their target RNAs or RNP complexes. This mechanism may underlie the functions of
      DEAD-box proteins by allowing them to generate local rearrangements without
      disrupting the global structures of their targets.

PMID- 19088197
TI  - The co-chaperone BAG3 regulates Herpes Simplex Virus replication.
AB  - Viruses as obligate intracellular parasites use host cell proteins to ensure
      efficient replication and spread. Cellular proteins are required for several
      stages of a virus life cycle. Here, we identify BAG3, a co-chaperone, as a
      regulator of herpes virus immediate early gene expression. We report that a
      herpes simplex virus lacking the gene encoding a potent transcriptional
      activator, ICP0, is compromised for replication in cells silenced for BAG3 in a
      multiplicity of infection-dependent manner. We also show a requirement for BAG3
      to augment virus gene expression and demonstrate that the co-chaperone acts
      independently of promyelocytic leukemia to increase herpes simplex virus
      replication.

PMID- 19088198
TI  - Oncogenic kinase NPM/ALK induces through STAT3 expression of immunosuppressive
      protein CD274 (PD-L1, B7-H1).
AB  - The mechanisms of malignant cell transformation caused by the oncogenic, chimeric
      nucleophosmin (NPM)/anaplastic lymphoma kinase (ALK) remain only partially
      understood, with most of the previous studies focusing mainly on the impact of
      NPM/ALK on cell survival and proliferation. Here we report that the NPM/ALK
      carrying T cell lymphoma (ALK+TCL) cells strongly express the immunosuppressive
      cell-surface protein CD274 (PD-L1, B7-H1), as determined on the mRNA and protein
      level. The CD274 expression is strictly dependent on the expression and enzymatic
      activity of NPM/ALK, as demonstrated by inhibition of the NPM/ALK function in
      ALK+TCL cells by the small molecule ALK inhibitor CEP-14083 and by documenting
      CD274 expression in IL-3-depleted BaF3 cells transfected with the wild-type
      NPM/ALK, but not the kinase-inactive NPM/ALK K210R mutant or empty vector alone.
      NPM/ALK induces CD274 expression by activating its key signal transmitter,
      transcription factor STAT3. STAT3 binds to the CD274 gene promoter in vitro and
      in vivo, as shown in the gel electromobility shift and chromatin
      immunoprecipitation assays, and is required for the PD-L1 gene expression, as
      demonstrated by siRNA-mediated STAT3 depletion. These findings identify an
      additional cell-transforming property of NPM/ALK and describe a direct link
      between an oncoprotein and an immunosuppressive cell-surface protein. These
      results also provide an additional rationale to therapeutically target NPM/ALK
      and STAT3 in ALK+TCL. Finally, they suggest that future immunotherapeutic
      protocols for this type of lymphoma may need to include the inhibition of NPM/ALK
      and STAT3 to achieve optimal clinical efficacy.

PMID- 19088199
TI  - SOCS3 drives proteasomal degradation of indoleamine 2,3-dioxygenase (IDO) and
      antagonizes IDO-dependent tolerogenesis.
AB  - Despite their common ability to activate intracellular signaling through
      CD80/CD86 molecules, cytotoxic T lymphocyte antigen 4 (CTLA-4)-Ig and CD28-Ig
      bias the downstream response in opposite directions, the latter promoting
      immunity, and CTLA-4-Ig tolerance, in dendritic cells (DCs) with opposite but
      flexible programs of antigen presentation. Nevertheless, in the absence of
      suppressor of cytokine signaling 3 (SOCS3), CD28-Ig-and the associated, dominant
      IL-6 response-become immunosuppressive and mimic the effect of CTLA-4-Ig,
      including a high functional expression of the tolerogenic enzyme indoleamine 2,3
      dioxygenase (IDO). Here we show that forced SOCS3 expression antagonized CTLA-4
      Ig activity in a proteasome-dependent fashion. Unrecognized by previous studies,
      IDO appeared to possess two tyrosine residues within two distinct putative
      immunoreceptor tyrosine-based inhibitory motifs, VPY(115)CEL and LLY(253)EGV. We
      found that SOCS3-known to interact with phosphotyrosine-containing peptides and
      be selectively induced by CD28-Ig/IL-6-would bind IDO and target the IDO/SOCS3
      complex for ubiquitination and subsequent proteasomal degradation. This event
      accounted for the ability of CD28-Ig and IL-6 to convert otherwise tolerogenic,
      IDO-competent DCs into immunogenic cells. Thus onset of immunity in response to
      antigen within an early inflammatory context requires that IDO be degraded in
      tolerogenic DCs. In addition to identifying SOCS3 as a candidate signature for
      mouse DC subsets programmed to direct immunity, this study demonstrates that IDO
      undergoes regulatory proteolysis in response to immunogenic stimuli.

PMID- 19088200
TI  - Maintenance of host variation in tolerance to pathogens and parasites.
AB  - Tolerance and resistance provide hosts with two distinct defense strategies
      against parasitism. In resistance the hosts "fight" the parasite directly,
      whereas in tolerance the hosts fight the disease by ameliorating the damage that
      infection causes. There is increasing recognition that the two mechanisms may
      exhibit very different evolutionary behaviors. Although empirical work has often
      noted considerable variance in tolerance within hosts, theory has predicted the
      fixation of tolerance due to positive frequency dependence through a feedback
      with disease prevalence. Here we reconcile these findings through a series of
      dynamic game theoretical models. We emphasize that there is a crucial distinction
      between tolerance to the effects of disease-induced mortality and tolerance to
      the effect of the disease-induced reductions in fecundity. Only mortality
      tolerance has a positive effect on parasite fitness, whereas sterility tolerance
      is neutral and may therefore result in polymorphisms. The nature of the costs to
      defense and their relationship to trade-offs between resistance and tolerance are
      crucial in determining the likelihood of variation, whereas the co-evolution of
      the parasite will not affect diversity. Our findings stress that it is important
      to measure the effects of different mechanisms on characteristics that affect the
      epidemiology of the parasite to completely understand the evolutionary dynamics
      of defense.

PMID- 19088201
TI  - ATP hydrolysis is required for DEAD-box protein recycling but not for duplex
      unwinding.
AB  - DEAD-box proteins, the largest helicase family, catalyze ATP-dependent remodeling
      of RNA-protein complexes and the unwinding of RNA duplexes. Because DEAD-box
      proteins hydrolyze ATP in an RNA-dependent fashion, the energy provided by ATP
      hydrolysis is commonly assumed to drive the energetically unfavorable duplex
      unwinding. Here, we show efficient unwinding of stable duplexes by several DEAD
      box proteins in the presence of the nonhydrolyzable ATP analog ADP-beryllium
      fluoride. Another ATP analog, ADP-aluminum fluoride, does not promote unwinding.
      The findings show that the energy from ATP hydrolysis is dispensable for strand
      separation. ATP binding, however, appears necessary. ATP hydrolysis is found to
      be required for fast enzyme release from the RNA and multiple substrate turnovers
      and thus for enzyme recycling.

PMID- 19088202
TI  - E3 ligase activity of BRCA1 is not essential for mammalian cell viability or
      homology-directed repair of double-strand DNA breaks.
AB  - Hereditary cases of breast and ovarian cancer are often attributed to germ-line
      mutations of the BRCA1 tumor suppressor gene. Although BRCA1 is involved in
      diverse cellular processes, its role in the maintenance of genomic integrity may
      be a key component of its tumor suppression activity. The protein encoded by
      BRCA1 interacts in vivo with the related BARD1 protein to form a heterodimeric
      complex that acts as a ubiquitin E3 ligase. Because the enzymatic activity of the
      BRCA1/BARD1 heterodimer is conserved over a broad phylogenetic range, it is
      thought to be critical for the central functions of BRCA1. To test this
      hypothesis, we have generated isogenic clones of embryonic stem cells that do or
      do not express an enzymatically proficient Brca1 polypeptide. Surprisingly, cells
      lacking the ubiquitin ligase activity of BRCA1 are viable and do not accumulate
      spontaneous cytogenetic rearrangements. Gene targeting efficiencies are modestly
      reduced in these cells, and chromosomal rearrangements arise at elevated rates in
      response to genotoxic stress. Nonetheless, cells lacking Brca1 enzymatic activity
      are not hypersensitive to the DNA cross-linking agent mitomycin C. They also form
      Rad51 focus in response to ionizing radiation and repair chromosome breaks by
      homologous recombination at wild-type levels. These results indicate that key
      aspects of BRCA1 function in genome maintenance, including its role in homology
      directed repair of double-strand DNA breaks, do not depend on the E3 ligase
      activity of BRCA1.

PMID- 19088203
TI  - IRF4 is essential for IL-21-mediated induction, amplification, and stabilization
      of the Th17 phenotype.
AB  - Differentiation of murine T-helper (Th) 17 cells is induced by antigenic
      stimulation and the sequential action of the cytokines IL-6, IL-21, and IL-23,
      along with TGFbeta. Current dogma proposes that IL-6 induces IL-21, which, in a
      STAT3-dependent manner, amplifies its own transcription, contributes to IL-17
      production, and, moreover, promotes the expression of the IL-23 receptor. This,
      in turn, prepares cells for IL-23-mediated stabilization of the Th17 phenotype.
      Here we demonstrate that these effects of IL-21 on Th17 differentiation are
      completely dependent on IFN regulatory factor 4 (IRF4). After culturing in the
      presence of IL-21 plus TGFbeta, IRF4-deficient (Irf4(-/-)) Th cells showed a
      profound intrinsic defect in IL-17 production and in the autocrine IL-21 loop.
      Likewise, the levels of IL-23 receptor and the lineage-specific orphan nuclear
      receptors RORalpha and RORgammat were diminished, whereas the T regulatory (Treg)
      transcription factor forkhead box P3 (Foxp3) was strongly up-regulated,
      consistent with the reciprocal relationship between Th17 and Treg development.
      Despite this loss of IL-21 functions, IL-21-induced STAT3 activation was
      unimpaired and induced normal Socs3 expression. Forced expression of Foxp3 in WT
      cells inhibited IL-21-mediated IL-17 production, suggesting that the increase in
      Foxp3 contributes to the Irf4(-/-) phenotype. Additionally, the low levels of
      RORalpha and RORgammat are also partially responsible, because simultaneous
      overexpression of both proteins restored IL-17 production in Irf4(-/-) cells to
      some extent. These data highlight IRF4 as a decisive factor during the IL-21
      mediated steps of Th17 development by influencing the balance of Foxp3, RORalpha,
      and RORgammat.

PMID- 19088205
TI  - A two-dimensional computational study on the fluid-structure interaction cause of
      wing pitch changes in dipteran flapping flight.
AB  - In this study, the passive pitching due to wing torsional flexibility and its
      lift generation in dipteran flight were investigated using (a) the non-linear
      finite element method for the fluid-structure interaction, which analyzes the
      precise motions of the passive pitching of the wing interacting with the
      surrounding fluid flow, (b) the fluid-structure interaction similarity law, which
      characterizes insect flight, (c) the lumped torsional flexibility model as a
      simplified dipteran wing, and (d) the analytical wing model, which explains the
      characteristics of the passive pitching motion in the simulation. Given
      sinusoidal flapping with a frequency below the natural frequency of the wing
      torsion, the resulting passive pitching in the steady state, under fluid damping,
      is approximately sinusoidal with the advanced phase shift. We demonstrate that
      the generated lift can support the weight of some Diptera.

PMID- 19088204
TI  - Trop2 identifies a subpopulation of murine and human prostate basal cells with
      stem cell characteristics.
AB  - The epithelium of the adult prostate contains 3 distinct cell types: basal,
      luminal, and neuroendocrine. Tissue-regenerative activity has been identified
      predominantly from the basal cells, isolated by expression of CD49f and stem cell
      antigen-1 (Sca-1). An important question for the field is whether all basal cells
      have stem cell characteristics. Prostate-specific microarray databases were
      interrogated to find candidate surface antigens that could subfractionate the
      basal cell population. Tumor-associated calcium signal transducer 2
      (TACSTD2/Trop2/M1S1/GA733-1) was identified because it was enriched after
      castration, in prostate sphere cells and in the basal fraction. In the murine
      prostate, Trop2 shows progenitor characteristics such as localization to the
      region of the gland proximal to the urethra and enrichment for sphere-forming and
      colony-forming cells. Trop2 subfractionates the basal cells into 2 populations,
      both of which express characteristic basal cell markers by quantitative PCR.
      However, only the basal cells expressing high levels of Trop2 were able to
      efficiently form spheres in vitro. In the human prostate, where Sca-1 is not
      expressed, sphere-forming progenitor cells were also isolated based on high
      expression of Trop2 and CD49f. Trop2-expressing murine basal cells could
      regenerate prostatic tubules in vivo, whereas the remaining basal cells had
      minimal activity. Evidence was found for basal, luminal, and neuroendocrine cells
      in prostatic tubules regenerated from Trop2(hi) basal cells. In summary,
      functionally distinct populations of cells exist within the prostate basal
      compartment and an epithelial progenitor can give rise to neuroendocrine cells in
      vivo.

PMID- 19088206
TI  - Intense echolocation calls from two 'whispering' bats, Artibeus jamaicensis and
      Macrophyllum macrophyllum (Phyllostomidae).
AB  - Bats use echolocation to exploit a variety of habitats and food types. Much
      research has documented how frequency-time features of echolocation calls are
      adapted to acoustic constraints imposed by habitat and prey but emitted sound
      intensities have received little attention. Bats from the family of
      Phyllostomidae have been categorised as low intensity (whispering) gleaners,
      assumed to emit echolocation calls with low source levels (approximately 70 dB
      SPL measured 10 cm from the bat's mouth). We used a multi-microphone array to
      determine intensities emitted from two phyllostomid bats from Panama with
      entirely different foraging strategies. Macrophyllum macrophyllum hunts insects
      on the wing and gaffs them with its tail membrane and feet from or above water
      surfaces whereas Artibeus jamaicensis picks fruit from vegetation with its mouth.
      Recordings were made from bats foraging on the wing in a flight room. Both
      species emitted surprisingly intense signals with maximum source levels of 105 dB
      SPL r.m.s. for M. macrophyllum and 110 dB SPL r.m.s. for A. jamaicensis, hence
      much louder than a ;whisper'. M. macrophyllum was consistently loud (mean source
      level 101 dB SPL) whereas A. jamaicensis showed a much more variable output,
      including many faint calls and a mean source level of 96 dB SPL. Our results
      support increasing evidence that echolocating bats in general are much louder
      than previously thought. We discuss the importance of loud calls and large output
      flexibility for both species in an ecological context.

PMID- 19088207
TI  - Powered ankle exoskeletons reveal the metabolic cost of plantar flexor mechanical
      work during walking with longer steps at constant step frequency.
AB  - We examined the metabolic cost of plantar flexor muscle-tendon mechanical work
      during human walking. Nine healthy subjects walked at constant step frequency on
      a motorized treadmill at speeds corresponding to 80% (1.00 m s(-1)), 100% (1.25 m
      s(-1)), 120% (1.50 m s(-1)) and 140% (1.75 m s(-1)) of their preferred step
      length (L(*)) at 1.25 m s(-1). In each condition subjects donned robotic ankle
      exoskeletons on both legs. The exoskeletons were powered by artificial pneumatic
      muscles and controlled using soleus electromyography (i.e. proportional
      myoelectric control). We measured subjects' metabolic energy expenditure and
      exoskeleton mechanics during both unpowered and powered walking to test the
      hypothesis that ankle plantarflexion requires more net metabolic power (W kg(-1))
      at longer step lengths for a constant step frequency (i.e. preferred at 1.25 m s(
      1)). As step length increased from 0.8 L(*) to 1.4 L(*), exoskeletons delivered
      approximately 25% more average positive mechanical power (P=0.01; +0.20+/-0.02 W
      kg(-1) to +0.25+/-0.02 W kg(-1), respectively). The exoskeletons reduced net
      metabolic power by more at longer step lengths (P=0.002; -0.21+/-0.06 W kg(-1) at
      0.8 L(*) and -0.70+/-0.12 W kg(-1) at 1.4 L(*)). For every 1 J of exoskeleton
      positive mechanical work subjects saved 0.72 J of metabolic energy ('apparent
      efficiency'=1.39) at 0.8 L(*) and 2.6 J of metabolic energy ('apparent
      efficiency'=0.38) at 1.4 L(*). Declining ankle muscle-tendon ;apparent
      efficiency' suggests an increase in ankle plantar flexor muscle work relative to
      Achilles' tendon elastic energy recoil during walking with longer steps. However,
      previously stored elastic energy in Achilles' tendon still probably contributes
      up to 34% of ankle muscle-tendon positive work even at the longest step lengths
      we tested. Across the range of step lengths we studied, the human ankle muscle
      tendon system performed 34-40% of the total lower-limb positive mechanical work
      but accounted for only 7-26% of the net metabolic cost of walking.

PMID- 19088208
TI  - Mechanics and energetics of incline walking with robotic ankle exoskeletons.
AB  - We examined healthy human subjects wearing robotic ankle exoskeletons to study
      the metabolic cost of ankle muscle-tendon work during uphill walking. The
      exoskeletons were powered by artificial pneumatic muscles and controlled by the
      user's soleus electromyography. We hypothesized that as the demand for net
      positive external mechanical work increased with surface gradient, the positive
      work delivered by ankle exoskeletons would produce greater reductions in users'
      metabolic cost. Nine human subjects walked at 1.25 m s(-1) on gradients of 0%,
      5%, 10% and 15%. We compared rates of O(2) consumption and CO(2) production,
      exoskeleton mechanics, joint kinematics, and surface electromyography between
      unpowered and powered exoskeleton conditions. On steeper inclines, ankle
      exoskeletons delivered more average positive mechanical power (P<0.0001; +0.37+/
      0.03 W kg(-1) at 15% grade and +0.23+/-0.02 W kg(-1) at 0% grade) and reduced
      subjects' net metabolic power by more (P<0.0001; -0.98+/-0.12 W kg(-1) at 15%
      grade and -0.45+/-0.07 W kg(-1) at 0% grade). Soleus muscle activity was reduced
      by 16-25% when wearing powered exoskeletons on all surface gradients (P<0.0008).
      The ;apparent efficiency' of ankle muscle-tendon mechanical work decreased from
      0.53 on level ground to 0.38 on 15% grade. This suggests a decreased contribution
      from previously stored Achilles' tendon elastic energy and an increased
      contribution from actively shortening ankle plantar flexor muscle fibers to ankle
      muscle-tendon positive work during walking on steep uphill inclines. Although
      exoskeletons delivered 61% more mechanical work at the ankle up a 15% grade
      compared with level walking, relative reductions in net metabolic power were
      similar across surface gradients (10-13%). These results suggest a shift in the
      relative distribution of mechanical power output to more proximal (knee and hip)
      joints during inclined walking.

PMID- 19088209
TI  - Ligand-specific induction of endocytosis in taste receptor cells.
AB  - We demonstrate a ligand-specific induction of endocytosis in cells of juvenile
      brown trout taste buds. The process is fast, massive and selective, as only a few
      cells in each taste buds are stained by exposure of the oral cavity to the taste
      stimulant l-cysteine together with a dye at 20 degrees C. Low temperature (+2
      degrees C) and disruption of microtubules with nocodazole caused a substantial
      reduction in the number of taste cells stained, indicating endocytic uptake of
      dye and transport towards the cell soma in vesicles. As endocytosis is evoked by
      the presence of ligands, it is most likely that the stained cells are the so
      called receptor cells, which have taste receptors and the molecular machinery for
      downstream processing. The number of stained taste cells and taste buds
      containing stained taste cells increased with the concentration of l-cysteine.
      Control experiments with different dyes revealed great variability in the ability
      to induce staining on their own. In particular, Texas Red dextran was efficient
      and stained many cells within each taste bud. Behavioural experiments
      demonstrated that Texas Red dextran is a deterrent taste substance for brown
      trout. In fish first exposed to the stimulant l-cysteine plus a dye and
      subsequently to a deterrent, either Texas Red, or glycine, the majority of
      stained cells were found in separate taste receptor cells, indicating that the
      majority of taste receptors for stimulants and deterrents are expressed in
      separate taste buds. These results also strengthen the assumption that the
      stained cells take part in the initiation of taste processes that are related to
      perception. The functional implication of the induced endocytosis is discussed.

PMID- 19088210
TI  - Swimming for your life: locomotor effort and oxygen consumption during the green
      turtle (Chelonia mydas) hatchling frenzy.
AB  - Swimming effort and oxygen consumption of newly emerged green turtle Chelonia
      mydas hatchlings was measured simultaneously and continuously for the first 18 h
      of swimming after hatchlings entered the water. Oxygen consumption was tightly
      correlated to swimming effort during the first 12 h of swimming indicating that
      swimming is powered predominantly by aerobic metabolism. The patterns of swimming
      effort and oxygen consumption could be divided into three distinct phases: (1)
      the rapid fatigue phase from 0 to 2 h when the mean swim thrust decreased from 45
      to 30 mN and oxygen consumption decreased from 33 to 18 ml h(-1); (2) the slow
      fatigue phase from 2 to 12 h when the mean swim thrust decreased from 30 to 22 mN
      and oxygen consumption decreased from 18 to 10 ml h(-1); and (3) the sustained
      effort phase from 12 to 18 h when mean swim thrust averaged 22 mN and oxygen
      consumption averaged 10 ml h(-1). The decrease in mean swim thrust was caused by
      a combination of a decrease in front flipper stroke rate during a power stroking
      bout, a decrease in mean maximum thrust during a power stroking bout and a
      decrease in the proportion of time spent power stroking. Hence hatchlings
      maximise their swimming thrust as soon as they enter the water, a time when a
      fast swimming speed will maximise the chance of surviving the gauntlet of
      predators inhabiting the shallow fringing reef before reaching the relative
      safety of deeper water.

PMID- 19088211
TI  - Activity of the pituitary-gonadal axis is increased prior to the onset of
      spawning migration of chum salmon.
AB  - The activity of the pituitary-gonadal axis (PG axis) in pre-migratory and homing
      chum salmon was examined because endocrine mechanisms underlying the onset of
      spawning migration remain unknown. Pre-migratory fish were caught in the central
      Bering Sea in June, July and September 2001, 2002 and 2003, and in the Gulf of
      Alaska in February 2006. They were classified into immature and maturing adults
      on the basis of gonadal development. The maturing adults commenced spawning
      migration to coastal areas by the end of summer, because almost all fish in the
      Bering Sea were immature in September. In the pituitaries of maturing adults, the
      copy numbers of FSHbeta mRNA and the FSH content were 2.5- to 100-fold those of
      the immature fish. Similarly, the amounts of LHbeta mRNA and LH content in the
      maturing adults were 100- to 1000-fold those of immature fish. The plasma levels
      of testosterone, 11-ketotestosterone and estradiol were higher than 10 nmol l(-1)
      in maturing adults, but lower than 1.0 nmol l(-1) in immature fish. The increase
      in the activity of the PG-axis components had already initiated in the maturing
      adults while they were still in the Gulf of Alaska in winter. In the homing
      adults, the pituitary contents and the plasma levels of gonadotropins and plasma
      sex steroid hormones peaked during upstream migration from the coast to the natal
      hatchery. The present results thus indicate that the seasonal increase in the
      activity of the PG axis is an important endocrine event that is inseparable from
      initiation of spawning migration of chum salmon.

PMID- 19088212
TI  - Habitat temperature is an important determinant of cholesterol contents in
      copepods.
AB  - Effects of habitat and acclimation temperature on cholesterol contents were
      examined in oceanic and inshore species of copepods. The cholesterol content of
      five species of thermally acclimated copepods was determined, and nine species
      (representing six families) were sampled to assess the role of habitat
      temperature. The species selected have maximum habitat temperatures (and
      temperature tolerances) that vary at least twofold. Levels of dietary cholesterol
      required to achieve maximum growth were also studied at different acclimation
      temperatures in a eurythermal copepod. Both eggs and copepodites of Calanus
      finmarchicus had higher cholesterol levels at the warm acclimation temperature
      (16 degrees C) than at the cooler temperature (6 degrees C). Neither Acartia
      tonsa, Acartia hudsonica, Temora longicornis nor Eurytemora affinis altered
      cholesterol contents with acclimation temperature. Maximum growth rates were
      achieved at fourfold higher concentrations of dietary cholesterol in warm
      acclimated Eurytemora affinis than in cold-acclimated animals. The most
      consistent trend is the positive relationship between cholesterol content and
      habitat temperature. Species residing in warmer habitats (e.g. Centropages
      typicus, Eurytemora affinis) had approximately twice the cholesterol of species
      living in colder waters (e.g. Calanus glacialis, Euchaeta norvegica). A similar
      pattern was observed for comparisons of species within genera (Calanus, Acartia
      and Centropages), with the species abundant at lower latitudes having more
      cholesterol than the northern congener. These data indicate that habitat
      temperature is an important determinant of cholesterol content, and cholesterol
      endows membranes with the stability required for a range of body temperatures.

PMID- 19088213
TI  - Multiplicity of expression of Na+,K+-ATPase {alpha}-subunit isoforms in the gill
      of Atlantic salmon (Salmo salar): cellular localisation and absolute
      quantification in response to salinity change.
AB  - The ability to reverse the net direction of gill ion transport in response to a
      salinity change is critical for euryhaline teleosts and involves a complex
      cellular and molecular remodelling of the gill epithelium. The present study
      aimed to clarify the cellular localisation and exact quantitative inter
      relationship of Na(+),K(+)-ATPase alpha- and beta-subunit transcripts in Atlantic
      salmon gill during salinity change. The combined expression level of all alpha
      isoforms in the gill increased by 100% after freshwater (FW) to seawater (SW)
      transfer. The alpha(1a) and alpha(1b) isoforms were both in the range 1-6 amol 20
      ng(-1) total RNA; alpha(1a) decreased and alpha(1b) increased after SW-transfer,
      their ratio changing from 5:1 in FW to 0.26:1 in SW. The alpha(1c) and alpha(3)
      levels were 10- and 100-fold lower, respectively. The beta(1)-subunit mRNA level
      was 0.1-0.3 amol 20 ng(-1) total RNA, thus much lower than the sum of alpha
      subunits. Even though increasing 3-fold after SW-transfer, beta-subunit
      availability may still limit functional pump synthesis. The mRNAs of the
      predominant alpha(1a) and alpha(1b) isoforms were localised by in situ
      hybridisation in specific gill cells of both FW and SW salmon. Labelling occurred
      mainly in presumed chloride cells and cells deep in the filament but occasionally
      also on lamellae. Overall, the salinity-induced variation in labelling pattern
      and intensity matched the quantification data. In conclusion, the predominant
      switching of Na(+),K(+)-ATPase alpha-subunit isoform mRNA during salinity
      acclimation reflects a marked remodelling of mitochondrion-rich cells (MRCs) in
      the gill and probably tuning of the pump performance to accomplish a net reversal
      of gill ion transport in hypo- and hypertonic environments.

PMID- 19088214
TI  - Sex-specific effects of prenatal testosterone on nestling plasma antioxidant
      capacity in the zebra finch.
AB  - Trans-generational transfer of non-genetic, maternal resources such as hormones
      can have a substantial influence on offspring phenotype in many vertebrate
      species. In birds, maternal androgens enhance both growth and competitive
      behaviour, but also suppress the immune system. It has been hypothesised that
      high levels of egg androgens could also influence the prooxidant-antioxidant
      balance through their positive effect on growth and metabolism. We tested this
      hypothesis in the zebra finch (Taeniopygia guttata). Eggs were injected with
      testosterone dissolved in sesame oil or sesame oil only (control). We
      subsequently assessed the effect of the egg hormone manipulation on nestling
      growth and nestling plasma total antioxidant capacity (TAC). Growth rates of
      zebra finch nestlings were not significantly affected by egg hormone treatment.
      However, male offspring hatched from eggs with experimentally elevated
      testosterone had reduced plasma TAC at 10 days of age compared with male
      offspring hatching from control eggs. At the age of 34 days, males had similar
      plasma TAC irrespective of egg treatment. No effects of egg testosterone
      manipulation on nestling plasma TAC were found in females. Our results
      demonstrate that embryonic exposure to elevated levels of testosterone modulates
      chick antioxidant status, but this seems to be independent of chick growth. Sex
      specific effects of prenatal testosterone on plasma TAC of zebra finch nestlings
      may have important consequences for sex allocation.

PMID- 19088215
TI  - Influence of flexibility on the aerodynamic performance of a hovering wing.
AB  - In the present study, a computational investigation was carried out to understand
      the influence of flexibility on the aerodynamic performance of a hovering wing. A
      flexible, two-dimensional, two-link model moving within a viscous fluid was
      considered. The Navier-Stokes equations governing the fluid dynamics were solved
      together with the equations governing the structural dynamics by using a strongly
      coupled fluid-structure interaction scheme. Harmonic kinematics was used to
      prescribe the motions of one of the links, thus effectively reducing the wing to
      a single degree-of-freedom oscillator. The wing's flexibility was characterized
      by the ratio of the flapping frequency to the natural frequency of the structure.
      Apart from the rigid case, different values of this frequency ratio (only in the
      range of 1/2 to 1/6) were considered at the Reynolds numbers of 75, 250 and 1000.
      It was found that flexibility can enhance aerodynamic performance and that the
      best performance is realized when the wing is excited by a non-linear resonance
      at 1/3 of the natural frequency. Specifically, at Reynolds numbers of 75, 250 and
      1000, the aerodynamic performance that is characterized by the ratio of lift
      coefficient to drag coefficient is respectively increased by 28%, 23% and 21%
      when compared with the corresponding ratios of a rigid wing driven with the same
      kinematics. For all Reynolds numbers, the lift generated per unit driving power
      is also enhanced in a similar manner. The wake capture mechanism is enhanced, due
      to a stronger flow around the wing at stroke reversal, resulting from a stronger
      end of stroke vortex at the trailing edge. The present study provides some clues
      about how flexibility affects the aerodynamic performance in low Reynolds number
      flapping flight. In addition, it points to the importance of considering non
      linear resonances for enhancing aerodynamic performance.

PMID- 19088216
TI  - Jumping strategies and performance in shore bugs (Hemiptera, Heteroptera,
      Saldidae).
AB  - The jumping movements of the hemipteran shore bug (Saldula saltatoria, sub-order
      Heteroptera, family Saldidae) were analysed from sequences of images captured at
      5000 frames s(-1). Adult Saldula weigh approximately 2.1 mg and are approximately
      3.5 mm long. The hind legs that propel jumping are 180% longer than the front
      legs and 90% of body length, but non-jumping species in the same family have
      longer hind legs relative to the lengths of their bodies. Jumps were powered by
      large trochanteral depressor muscles in the thorax in two different strategies.
      In the first (used in 24% of jumps analysed), a jump was propelled by
      simultaneous extension of the two hind legs powered by rapid depression movements
      about the coxo-trochanteral joints, while both pairs of wings remained closed. In
      the second strategy (74% of jumps), the wings were opened before the hind legs
      began to move. At take-off, the position of the wings was variable and could be 8
      21 ms into either elevation or depression. When the hind legs alone propelled a
      jump, the body was accelerated in 3.97+/-0.111 ms at a take-off angle of 52+/-6.5
      degrees to a take-off velocity of 1.27+/-0.119 m s(-1); when the wings also
      moved, the body was accelerated in 3.86+/-0.055 ms at a take-off angle of 58+/
      1.7 degrees to a take-off velocity of 1.29+/-0.032 m s(-1). These values are not
      different in the two jumping strategies. In its best jumps the take-off velocity
      reached 1.8 m s(-1) so that Saldula experienced an average acceleration of 529 m
      s(-2), equivalent to almost 54 g, expended 3.4 microJ of energy, while exerting a
      force of 1.1 m N. The power requirements for jumping indicate that a catapult
      mechanism must be used in which the trochanteral depressor muscles contract and
      store energy in advance of a jump. These jumps should propel it to a height of
      105 mm or 30 times its body length and distances of 320 mm. The two jumping
      strategies achieve the same jumping performance.

PMID- 19088217
TI  - Kinematics of benthic suction feeding in Callichthyidae and Mochokidae, with
      functional implications for the evolution of food scraping in catfishes.
AB  - Food scraping has independently evolved twice from suction feeding in the
      evolution of catfishes: within neotropical Loricarioidea and paleotropical
      Mochokidae. To gain insight in the evolutionary transitions associated with the
      evolution towards scraping, we analyzed prey capture kinematics in two species of
      benthic suction feeders which belong to taxa that are closely related to the
      scraper lineages (respectively, Corydoras splendens and Synodontis
      multipunctatus), and compared it to prey capture in a more distantly related,
      generalist suction feeder (Clarias gariepinus). Simultaneous ventral and lateral
      view high-speed videos were recorded to quantify the movements of the lower jaw,
      hyoid, pectoral girdle and neurocranium. Additionally, ellipse modeling was
      applied to relate head shape differences to buccal expansion kinematics.
      Similarly to what has been observed in scrapers, rotations of the neurocranium
      are minimal in the benthic suction feeders, and may consequently have facilitated
      the evolution of a scraping feeding mechanism. The hypothesis that fish with a
      more laterally compressed head rely more heavily on lateral expansion of the
      buccal cavity to generate suction, was confirmed in our sample of catfish
      species. Since an important contribution of lateral expansion of the head to
      suction may avoid the need for a strong, ventral depression of the mouth floor
      during feeding, we hypothesized that this may have allowed a closer association
      with the substrate in the ancestors of scrapers. However, our hypothesis was not
      supported by an ancestral state reconstruction, which suggests that scraping
      probably evolved from sub-terminal mouthed ancestors with dorsoventrally
      flattened heads.

PMID- 19088219
TI  - Decreased precision contributes to the hypoxic thermoregulatory response in
      lizards.
AB  - The decrease in body temperature (T(b)) observed in most vertebrate classes in
      response to hypoxia has been attributed to a regulated decrease in set-point,
      protecting organs against tissue death due to oxygen depletion. Hypoxia, however,
      imparts particular challenges to metabolic function which may, in turn, affect
      thermoregulation. In ectotherms, where thermoregulation is mainly behavioural,
      stressors that influence the propensity to move and respond to temperature
      gradients are expected to have an impact on thermoregulatory control. Using low
      oxygen as a potent stressor, we evaluated the variability and level of
      thermoregulation of inland bearded dragons. To examine the source of
      thermoregulatory variability, we studied their behaviour in an electronically
      controlled temperature-choice shuttle box, a constant temperature dual-choice
      shuttle box, and a linear thermal gradient. A significant increase in the size of
      the T(b) range was observed at the lowest oxygen concentration (4% O(2)),
      reflecting a decrease in thermoregulatory precision in the temperature-choice
      shuttle box. This was also accompanied by a drop of approximately 2-4 degrees C
      in T(b), the drop being greatest in situations where T(b) must be actively
      defended. Situations that force the lizards to continually choose temperatures,
      rather than passively remain at a given temperature, lead to an increase in the
      variability in the manifested T(b), which is further exaggerated in hypoxia. This
      study reveals that a decrease in thermoregulatory precision caused by a
      diminished propensity to move or effect appropriate thermoregulatory responses
      may be a contributing component in the lowering of selected body temperatures
      observed in many hypoxic ectotherms.

PMID- 19088218
TI  - Source, topography and excitatory effects of GABAergic innervation in cockroach
      salivary glands.
AB  - Cockroach salivary glands are innervated by dopaminergic and serotonergic
      neurons. Both transmitters elicit saliva secretion. We studied the distribution
      pattern of neurons containing gamma-aminobutyric acid (GABA) and their
      physiological role. Immunofluorescence revealed a GABA-immunoreactive axon that
      originates within the subesophageal ganglion at the salivary neuron 2 (SN2) and
      this extends within the salivary duct nerve towards the salivary gland. GABA
      positive fibers form a network on most acinar lobules and a dense plexus in the
      interior of a minor fraction of acinar lobules. Co-staining with anti-synapsin
      revealed that some putative GABAergic terminals seem to make pre-synaptic
      contacts with GABA-negative release sites. Many putative GABAergic release sites
      are at some distance from other synapses and at distance from the acinar tissue.
      Intracellular recordings from isolated salivary glands have revealed that GABA
      does not affect the basolateral membrane potential of the acinar cells directly.
      When applied during salivary duct nerve stimulation, GABA enhances the electrical
      response of the acinar cells and increases the rates of fluid and protein
      secretion. The effect on electrical cell responses is mimicked by the GABA(B)
      receptor agonists baclofen and SKF97541, and blocked by the GABA(B) receptor
      antagonists CGP52432 and CGP54626. These findings indicate that GABA has a
      modulatory role in the control of salivation, acting presynaptically on
      serotonergic and/or dopaminergic neurotransmission.

PMID- 19088220
TI  - The unequal influences of the left and right vagi on the control of the heart and
      pulmonary artery in the rattlesnake, Crotalus durissus.
AB  - Autonomic control of the cardiovascular system in reptiles includes sympathetic
      components but heart rate (f(H)), pulmonary blood flow (Q(pul)) and cardiac shunt
      patterns are primarily controlled by the parasympathetic nervous system. The
      vagus innervates both the heart and a sphincter on the pulmonary artery. The
      present study reveals that whereas both the left and right vagi influence f(H),
      it is only the left vagus that influences pulmonary vascular resistance. This is
      associated with the fact that rattlesnakes, in common with some other species of
      snakes, have a single functional lung, as the other lung regresses during
      development. Stimulation of the left cervical vagus in anaesthetised snakes
      slowed the heart and markedly reduced blood flow in the pulmonary artery whereas
      stimulation of the right cervical vagus slowed the heart and caused a small
      increase in stroke volume (V(S)) in both the systemic and pulmonary circulations.
      Central stimulation of either vagus caused small (5-10%) reductions in systemic
      blood pressure but did not affect blood flows or f(H). A bilateral
      differentiation between the vagi was confirmed by progressive vagotomy in
      recovered snakes. Transection of the left vagus caused a slight increase in f(H)
      (10%) but a 70% increase in Q(pul), largely due to an increase in pulmonary
      stroke volume (V(S,pul)). Subsequent complete vagotomy caused a 60% increase in
      f(H) accompanied by a slight rise in Q(pul), with no further change in V(S,pul).
      By contrast, transection of the right vagus elicited a slight tachycardia but no
      change in V(S,pul). Subsequent complete vagotomy was accompanied by marked
      increases in f(H), Q(pul) and V(S,pul). These data show that although the heart
      receives bilateral vagal innervation, the sphincter on the pulmonary artery is
      innervated solely by the left vagus. This paves the way for an investigation of
      the role of the cardiac shunt in regulating metabolic rate, as chronic left
      vagotomy will cause a pronounced left-right shunt in recovered animals, whilst
      leaving intact control of the heart, via the right vagus.

PMID- 19088221
TI  - The nearly columnar limbs of elephants are very different from the more flexed,
      spring action limbs of running mammals and birds.

PMID- 19088223
TI  - Effects of an aerobic exercise program on aerobic capacity, spatiotemporal gait
      parameters, and functional capacity in subacute stroke.
AB  - BACKGROUND: and objective. In spite of the challenges, engaging in exercise
      programs very early after stroke may positively influence aerobic capacity and
      stroke-related outcomes, including walking ability. The objective of this study
      was to evaluate the feasibility of adding aerobic cycle ergometer training to
      conventional rehabilitation early after stroke and to determine effects on
      aerobic capacity, walking ability, and health-related quality of life. METHODS: A
      prospective matched control design was used. All participants performed a graded
      maximal exercise test on a semi-recumbent cycle ergometer, spatiotemporal gait
      assessments, 6-Minute Walk Test, and Stroke Impact Scale. The Exercise group
      added 30 minutes of aerobic cycle ergometry to conventional inpatient
      rehabilitation 3 days/week until discharge; the Control group received
      conventional rehabilitation only. RESULTS: All Exercise participants (n = 23)
      completed the training without adverse effects. In the 18 matched pairs, both
      groups demonstrated improvements over time with a trend toward greater aerobic
      benefit in the Exercise group with 13% and 23% increases in peak VO(2) and work
      rate respectively, compared to 8% and 16% in the Control group (group-time
      interaction P = .71 and .62). A similar trend toward improved 6-Minute Walk Test
      distance (Exercise 53% vs Controls 23%, P = .23) was observed. CONCLUSION: Early
      aerobic training can be safely implemented without deleterious effects on stroke
      rehabilitation. A trend toward greater improvement in aerobic capacity and
      walking capacity suggests that such training may have an early beneficial effect
      and should be considered for inclusion in rehabilitation programs.

PMID- 19088224
TI  - Use of an electronic medical record system to support primary care
      recommendations to prevent, identify, and manage childhood obesity.
AB  - Many primary care physicians are not providing care that is consistent with
      recommendations to prevent, to identify, and to manage childhood obesity. This
      report presents modifications made to the electronic medical record system of a
      large pediatric health care system, using a quality improvement approach, to
      support these recommendations and office system changes. Although it is possible
      to make practice changes secondary to electronic medical record system
      enhancements, challenges to development and implementation exist.

PMID- 19088225
TI  - Health information systems and physician quality: role of the American board of
      pediatrics maintenance of certification in improving children's health care.
AB  - A second revolution in quality is occurring in US health care, as profound as the
      Flexner revolution almost 100 years ago. Systems issues are the basis for most of
      the concern, but physician quality and professional development are also
      important. Specialty board certification and maintenance of certification are key
      drivers of professional development and improvement of care. Physicians are now
      required to document that they can assess and improve quality of care. Functional
      health information systems are essential for this process.

PMID- 19088226
TI  - Policy and system strategies in promoting child health information systems,
      including the role of Medicaid, the state children's health insurance program,
      and public financing.
AB  - Government, through its unique roles as regulator, purchaser, provider, and
      facilitator, has an opportunity and an obligation to play a major role in
      accelerating the implementation of electronic health record systems and
      electronic health information exchange. Providers, who are expected to deliver
      appropriate care at designated locations at an appropriate cost, are dependent on
      health information technology for efficient effective health care. As state and
      federal governments move forward with health care purchasing reforms, they must
      take the opportunity to leverage policy and structure and to align incentives
      that enhance the potential for provider engagement in electronic health record
      adoption.

PMID- 19088227
TI  - Health information law in the context of minors.
AB  - This article presents a legal overview of privacy and autonomy considerations
      related to children in the context of health information technology adoption and
      use. All uses of health-related technologies take place within a legal framework
      that guides health care generally; the privacy laws and autonomy principles long
      predate health information technology and can be expected to shape its design and
      use. Furthermore, it is a legal tenet that technology advances shape the law, and
      this can be expected as health information technology use evolves. Most laws
      related to health care, medical practice, and the right to privacy are state
      based and subject to high variability. As the health information revolution
      increasingly eliminates the importance of geographic boundaries to health care,
      interstate tensions can be expected to grow. Health information privacy law is
      even more complex in the case of children, because the relationship between
      privacy law and children is itself complex. The law considers minor children to
      be deserving of special protection against harm and risk exposure, and this
      concern extends to privacy. Regardless of whether minors can shield health
      information from parents, it is clear that parents and children have the power to
      control the flow of information to and among entities. Although information
      protections may pose a higher standard where information about children is
      concerned, this fact should not overshadow the extent to which information can be
      used under existing legal principles. Over time, as the security and safety of
      information sharing are established, the law may yet evolve to permit a freer
      flow of information.

PMID- 19088228
TI  - Advancing patient-centered pediatric care through health information exchange:
      update from the American Health Information Community Personalized Health Care
      Workgroup.
AB  - The Personalized Health Care Workgroup of the American Health Information
      Community was formed to foster a broad, community-based approach to facilitate
      the incorporation of interoperable, clinically useful, genetic/genomic
      information and analytical tools into electronic health records, to support
      clinical decision-making. The Personalized Health Care Workgroup has developed a
      series of use cases that outline the informational needs of multiple stakeholders
      (eg, patients, clinicians, organizations, and systems) and describe the
      information systems necessary to connect these stakeholders at multiple levels.
      These use case scenarios offer a guide for standardized data elements and
      architecture that enable interoperability (content sharing) among different
      formats of patient electronic health records.

PMID- 19088229
TI  - The public role in promoting child health information technology.
AB  - The public sector plays an important role in promoting child health information
      technology. Public sector support is essential in 5 main aspects of child health
      information technology, namely, data standards, pediatric functions in health
      information systems, privacy policies, research and implementation funding, and
      incentives for technology adoption. Some innovations in health information
      technology for adult populations can be transferred to or adapted for children,
      but there also are unique needs in the pediatric population. Development of
      health information technology that addresses children's needs and effective
      adoption of that technology are critical for US children to receive care of the
      highest possible quality in the future.

PMID- 19088230
TI  - It is time! Accelerating the use of child health information systems to improve
      child health.
AB  - Articles in this issue show clearly the enormous impact that the use of health
      information technology can have on the quality of health care for children.
      However, they also point out the challenges that need to be overcome to realize
      fully the potential of health information technology to improve the quality and
      efficiency of health care.

PMID- 19088231
TI  - Alliance for pediatric quality: creating a community of practice to improve
      health care for America's children.
AB  - On any given day, hundreds of physicians, nurses, informaticists, health
      information management directors, and other health care providers are
      collaborating on how to improve health information technology systems for use in
      child health care. Many work in small communities of practice to share ideas, to
      find solutions, and to build innovations that support the goal of making
      electronic health record systems accessible by 2014. Together, they are a
      formidable virtual community aligned around a common strategy, to ensure that
      health information technology works for children. Each member in the community
      represents a children's hospital or pediatric practice affiliated with one of the
      4 major national pediatric organizations that constitute the Alliance for
      Pediatric Quality. The alliance works with the pediatric health information
      technology community to speed the adoption of pediatric data standards and to
      define data collection and reporting systems that would work for both quality
      improvement and electronic health record systems. With this foundation, hospitals
      and physicians should be better positioned to improve the quality of health care
      for US children by implementing technology equipped to care for children,
      actively participating in improvement initiatives, conducting meaningful
      measurement of care, and appropriately reporting for accountability.

PMID- 19088232
TI  - Linking children's health information systems: clinical care, public health,
      emergency medical systems, and schools.
AB  - This article describes health information systems used for children in a variety
      of settings (eg, clinical care, public health, emergency medicine systems, and
      schools) and their current ability to exchange information. The potential
      benefits from linking these systems are considered, as well as the barriers to
      linkage. In addition, an example of efforts linking information systems together
      is summarized, and conclusions are drawn from this example for future efforts.

PMID- 19088233
TI  - Data standards and improvement of quality and safety in child health care.
AB  - Progress in using information technology to achieve the goal of high-quality
      health care is hindered by the lack of coordinated data standards. To accelerate
      quality improvement in pediatrics, child health providers must participate
      actively in the creation of health care data standards. To do so will require far
      greater understanding on the part of pediatricians and other pediatric providers
      regarding the scope and role of data standards in advancing health information
      systems for children, as well as how data standards could improve quality in
      child health, what kinds of data standards hold the most promise for quality
      improvement in child health, and how child health professionals can engage in the
      work of creating data standards. Child health professionals in organized and
      academic medicine should participate in standards development organizations, to
      present the pediatric point of view as data standards emerge. They also should
      support efforts to certify electronic health record systems that include
      pediatric functionality. A major challenge to academic pediatrics is to prove
      that data standards can lead to improved health outcomes for children; this is
      only a compelling conjecture as of this writing.

PMID- 19088234
TI  - Use of health information technology by children's hospitals in the United
      States.
AB  - OBJECTIVE: The purpose of this study was to examine the adoption of health
      information technology by children's hospitals and to document barriers and
      priorities as they relate to health information technology adoption. METHODS:
      Primary data of interest were obtained through the use of a survey instrument
      distributed to the chief information officers of 199 children's hospitals in the
      United States. Data were collected on current and future use of a variety of
      clinical health information technology and telemedicine applications,
      organizational priorities, barriers to use of health information technology, and
      hospital and chief information officer characteristics. RESULTS: Among the 109
      responding hospitals (55%), common clinical applications included clinical
      scheduling (86.2%), transcription (85.3%), and pharmacy (81.9%) and laboratory
      (80.7%) information. Electronic health records (48.6%), computerized order entry
      (40.4%), and clinical decision support systems (35.8%) were less common. The most
      common barriers to health information technology adoption were vendors' inability
      to deliver products or services to satisfaction (85.4%), lack of staffing
      resources (82.3%), and difficulty in achieving end-user acceptance (80.2%). The
      most frequent priority for hospitals was to implement technology to reduce
      medical errors or to promote safety (72.5%). CONCLUSION: This first national look
      at health information technology use by children's hospitals demonstrates the
      progress in health information technology adoption, current barriers, and
      priorities for these institutions. In addition, the findings can serve as
      important benchmarks for future study in this area.

PMID- 19088235
TI  - Electronic results management in pediatric ambulatory care: qualitative
      assessment.
AB  - BACKGROUND: Electronic results management may improve the reliability and
      efficiency of test results management, but few studies have investigated this
      topic in pediatrics. METHODS: We conducted semi-structured, key informant
      interviews before and after implementation of electronic results management at 8
      pediatric ambulatory care practices. We also surveyed all pediatricians at 18
      practices (10 additional practices). All practices were members of Partners
      Healthcare and had been using an electronic health record when they were offered
      electronic results management. We assessed baseline processes for results
      management, barriers to electronic results management adoption, and the perceived
      impact of electronic results management on quality, efficiency, and provider
      satisfaction. RESULTS: From interviews, we found a range of processes in place to
      manage test results, but all practices reported losing some results and no
      practice tracked all test results from the time of ordering to parent/patient
      notification. Practices that fully adopted electronic results management reported
      gains in efficiency, reliability, timeliness, and provider satisfaction, whereas
      some partial adopters reported decreased efficiency and increased risk of lost
      test results. Barriers to electronic results management adoption included lack of
      inclusion of all ordered tests in the electronic results management system, user
      interface design issues, and lack of sufficient pediatric customization. Survey
      results (response rate: 62%) indicated that pediatricians thought electronic
      results management improved the quality and efficiency of care, with 72% of
      pediatricians reporting safer care and 63% reporting more-effective care.
      CONCLUSIONS: We found that pediatric practices have room for improvement in the
      management of test results, and electronic results management may be an effective
      method for improving the efficiency and safety of test results management.
      However, partial adoption of electronic results management may decrease
      efficiency and pose a threat to patient safety.

PMID- 19088236
TI  - Influence of pay-for-performance programs on information technology use among
      child health providers: the devil is in the details.
AB  - OBJECTIVE: Pay-for-performance programs are used to promote improved health care
      quality, often through increased use of health information technology. However,
      little is known about whether pay-for-performance programs influence the adoption
      of health information technology, especially among child health providers. This
      study explored how various pay-for-performance compensation methods are related
      to health information technology use. METHODS: Survey data from 1014 child health
      providers practicing in Florida were analyzed by using univariate and
      multivariate techniques. Questions asked about the adoption of electronic health
      records and personal digital assistants, as well as types of activities that
      affected child health provider compensation or income. RESULTS: The most common
      reported method to affect respondents' compensation was traditional productivity
      or billing (78%). Of the pay-for-performance-related methods of compensation,
      child health providers indicated that measures of clinical care (41%), patient
      surveys and experience (34%), the use of health information technology (29%), and
      quality bonuses or incentives (27%) were a major or minor factor in their
      compensation. In multivariate logistic regression analyses, only pay-for
      performance programs that compensated directly for health information technology
      use were associated with an increased likelihood of electronic health record
      system adoption. Pay-for-performance programs linking measures of clinical
      quality to compensation were positively associated with personal digital
      assistant use among child health providers. CONCLUSIONS: Pay-for-performance
      programs that do not directly emphasize health information technology use do not
      influence the adoption of electronic health records among Florida physicians
      treating children. Understanding how different pay-for-performance compensation
      methods incentivize health information technology adoption is important for
      improving quality.

PMID- 19088237
TI  - Pediatric personal health records: current trends and key challenges.
AB  - Personal health records may enhance pediatric care and outcomes. Few systems have
      been developed or customized for pediatrics, and evaluations are scarce. Special
      considerations in pediatrics include pediatric content such as growth charts,
      complex privacy and confidentiality considerations, and the changing
      developmental needs of children and adolescents.

PMID- 19088239
TI  - Report of colloquium I: the future of pediatric health care delivery and
      education--pondering imponderables to create an ideal residency in a world of
      critical uncertainties.
AB  - Participants of the first colloquium of the Residency Review and Redesign in
      Pediatrics (R(3)P) Project considered possible scenarios affecting pediatric
      practice over the next 15 to 20 years and speculated about the knowledge and
      skills that pediatricians would need to care for children, adolescents, and young
      adults in the future. They concluded that the imponderables and complexity of
      that undertaking fell into the category of a "wicked problem" with no unique
      solutions. The specifics of the future cannot be predicted, but the themes
      important to thinking about the future are clear and must be incorporated into
      thinking about pediatric residency education.

PMID- 19088238
TI  - Linking process to outcome: are we training pediatricians to meet evolving health
      care needs?
AB  - The Residency Review and Redesign in Pediatrics (R(3)P) Project began in 2005 and
      will have been completed in 2009. The purpose was to conduct a comprehensive
      reassessment of general pediatric residency education. The project convened 3
      major colloquia supplemented by numerous meetings of an R(3)P committee and by
      surveys of residents, subspecialty fellows, and generalist and subspecialty
      practitioners. A principal conclusion was that resident learning opportunities
      should be more flexibly directed toward the variety of career choices available
      to pediatricians. Another conclusion was that reasonable expectations for
      residency education are most likely if learning is regarded as an integrated
      continuum, beginning in medical school and continuing throughout a career in
      practice. The R(3)P Committee declined to create a list of recommendations for
      immediate changes in residency education; instead, it recommends that changes be
      based on evidence of education outcomes that are important to improving the
      health of children, adolescents, and young adults.

PMID- 19088240
TI  - Report of colloquium II: the theory and practice of graduate medical education-
      how do we know when we have made a "good doctor"?
AB  - Participants of the second colloquium of the Residency Review and Redesign in
      Pediatrics (R(3)P) Project considered 3 primary questions: What is a "good
      doctor"? How do we make one? and How do we know when we have made one? Experts
      from other countries and other medical specialties helped participants wrestle
      with these most basic questions. Participants emerged with a better feeling of
      the utility of different types of evaluations needed to determine resident
      competence. It was clear that the complexity of the task requires faculty
      education and development. Most important, it requires the ongoing commitment of
      all of pediatrics as we seek to link education directly to better health outcomes
      for children, adolescents, and young adults.

PMID- 19088241
TI  - Report of colloquium III: challenges for pediatric graduate medical education and
      how to meet them--a quality improvement approach to innovation in pediatric
      graduate medical education.
AB  - Participants of the third colloquium of the Residency Review and Redesign in
      Pediatrics (R(3)P) Project concluded that pediatricians who practice ambulatory,
      hospital-based, a combination of ambulatory and hospital-based, and subspecialty
      pediatrics are sufficiently different to justify differences in general pediatric
      residency training. This conclusion along with others of previous colloquia led
      to the creation of a list of goals for innovative change in residency education
      and a draft of a quality improvement process by which they might be achieved.

PMID- 19088242
TI  - General pediatrics resident perspectives on training decisions and career choice.
AB  - OBJECTIVE: Little is known regarding at what point during the training period
      residents in pediatrics make decisions on their future career choices. As part of
      a dedicated process of reexamining the structure of residency training in
      pediatrics, the American Board of Pediatrics sought information to better
      understand the influences, process, and sequencing of both residency program
      selection and career decision-making among residents. METHODS: All pediatrics
      resident physicians in all training programs in the United States and Canada (N =
      8290) received the survey as part of the general pediatrics in-training
      examination. The survey focused on exploring how and when pediatrics residents
      make career choices and assessed perceived flexibility of their individual
      pediatrics residency program. RESULTS: The response rate was 95%. Location was
      the most important factor in selecting a residency program for 42% of all
      residents. Almost half of the pediatrics residents planned to pursue fellowship
      training after residency, a proportion that changed little across the 3 training
      years (level 1: 47%; level 2: 49%; level 3: 47%). Those who planned to pursue a
      general pediatrics career (either with or without inpatient care) were more
      likely than those who intended to pursue fellowship training to report that
      lifestyle was the most important factor in their career choice (63% vs 21%).
      CONCLUSIONS: Not surprisingly, different priorities motivate pediatricians to
      pursue specific programs for training and specific career options. The finding
      that those with the highest priority regarding lifestyle are more likely to
      pursue generalist training has implications for the generalist workforce, because
      those persons may also be more likely to seek part-time employment. Lifestyle
      concerns may need to be addressed in subspecialty training and subsequent
      subspecialty careers to ensure a continued flow of residents into fellowship
      training.

PMID- 19088243
TI  - Pediatric fellows: perspectives on training and future scope of practice.
AB  - OBJECTIVE: Training for pediatric residents who intend to pursue fellowship
      differs little from training for residents who intend to practice general
      pediatrics. It is unknown how well residents who intend to pursue subspecialty
      training believe that residency prepares them for subspecialty fellowships or
      future careers. To characterize the strengths and weaknesses of residency
      training and the factors influencing subspecialty choice from the perspective of
      subspecialty fellows, we conducted a survey of current fellows on these issues.
      METHODS: A random sample of 1000 physicians who were entering their second or
      third year of fellowship in the United States in 2007 received a structured
      questionnaire by mail. The survey focused on decision-making in selection of
      residency and fellowship programs, strength of residency training in preparation
      for fellowship, and plans for future practice. RESULTS: The overall response rate
      was 81%. A majority of the fellows would not have shortened their general
      pediatrics residency before fellowship if given the option (64% [n = 482]).
      However, more than half (52% [n = 390]) of the fellows would have chosen a 2-year
      fellowship without research or scholarly activity over the current 3-year
      structure. Few current fellows believed they could have used any additional
      training in the areas of patient safety, coordination of care for children with
      complex illnesses, or patient communication. CONCLUSIONS: The finding that a
      large proportion of fellows would opt for shortened subspecialty training should
      prompt discussion and debate within the profession regarding the skills necessary
      for a pediatric subspecialist. Patient safety, physician-parent communication,
      and care coordination are emphasized primarily through informal training during
      residency. Although most clinicians believe themselves to be adequately prepared,
      research has identified gaps in clinician skills and understanding of these
      issues of great importance to patients and their families.

PMID- 19088244
TI  - Recently trained general pediatricians: perspectives on residency training and
      scope of practice.
AB  - OBJECTIVE: Because of the increase in both the prevalence and complexity of
      chronic diseases in children, there is heightened awareness of the need for
      general pediatricians to be prepared to comanage their patients with chronic
      disorders with subspecialists. It is not known currently how well prepared
      general pediatricians believe themselves to be for these roles after residency
      training. This study was conducted to determine the perspectives of recently
      trained general pediatricians in practice regarding their decisions on residency
      choice, career choice, and adequacy of training. METHODS: A random sample of 600
      generalists whose initial application for general pediatric certification
      occurred between 2002 and 2003 (4-5 years out of training) and 600 generalists
      who applied for board certification between 2005 and 2006 and who were not
      currently enrolled in or had completed subspecialty training (1-2 years out of
      training) received a structured questionnaire by mail. The survey focused on
      decision-making in selection of residency programs, strength of residency
      training in preparation for clinical care, and scope of practice. RESULTS: The
      overall response rate was 76%. The majority of generalists reported that their
      residency training was adequate in most subspecialty areas. However, a large
      proportion of generalists indicated that they could have used additional training
      in mental health (62% [n = 424]), sports medicine (51% [n = 345]), oral health
      (52% [n = 356]), and developmental/behavioral pediatrics (48% [n = 326]). Most
      generalist respondents reported that they are comfortable comanaging cases
      requiring subspecialty care with a subspecialist. However, generalist respondents
      without local access to subspecialists were more likely to report that they are
      comfortable managing patients who require subspecialty care. CONCLUSIONS: The
      training of general pediatricians, and the needs for their adequate preparation
      to care for patients, should be a dynamic process. As the nature and epidemiology
      of pediatric care change, our educational system must change as well.

PMID- 19088245
TI  - Recently trained pediatric subspecialists: perspectives on training and scope of
      practice.
AB  - OBJECTIVES: Little is known regarding the factors influencing the decision to
      pursue pediatric subspecialty fellowship training and the timing of when such a
      decision is made. In addition, there is no information regarding whether the
      general pediatrics training received in residency is perceived as valuable by
      subspecialists. This study was conducted to characterize the strengths and
      weaknesses of residency and fellowship training from the perspective of recently
      trained pediatric subspecialists and to assess their current and future career
      goals and intended scope of practice. METHODS: A random sample of 550
      subspecialists whose initial application for pediatric subspecialty certification
      occurred between 2002 and 2003 (4-5 years out of training) and 550 subspecialists
      who applied for board certification between 2005 and 2006 (1-2 years out of
      training) received a structured questionnaire by mail. The survey focused on
      decision-making in selection of residency and fellowship programs, strength of
      residency training in preparation for clinical care provision, and scope of
      current practice. RESULTS: The overall response rate was 77%. More than half
      (54%) of the recently trained subspecialists would have shortened either their
      pediatric residency or fellowship training if given the opportunity, and 7% were
      unsure. More than one third of the respondents made the decision to pursue
      subspecialty training before the start of residency (36% [n = 198]), whereas
      approximately half of them made this decision during the first (19% [n = 106]) or
      second (27% [n = 150]) year of residency. CONCLUSIONS: Many subspecialists would
      have been interested in modifications to their pediatric residency and fellowship
      training programs, which may reflect changing patterns of professional activities
      or the preferences of a younger generation of subspecialists. Given that a
      substantial proportion of subspecialists decide to pursue subspecialty training
      before or early in residency, greater flexibility in configuring some residency
      experiences to meet their career goals would be feasible.

PMID- 19088246
TI  - What can data tell us about the quality and relevance of current pediatric
      residency education?
AB  - The Residency Review and Redesign (R(3)P) Project relied on both qualitative and
      quantitative data in developing its recommendations regarding residency
      education. This article reviews quantitative data in the published literature of
      import to the R(3)P Project as well as findings by Freed and colleagues published
      in this supplement to Pediatrics. Primary questions of interest to the R(3)P
      Project included: What factors drive decision-making regarding residency
      selection? Do current training programs have the flexibility to meet the needs of
      residents, no matter what their career choice with pediatrics? What areas need
      greater focus within residency training? Should the length of training remain at
      36 months? Based on the available data, the R(3)P Project concluded that more
      diversity needs to be fostered with training programs. By promoting innovative
      and diverse approaches to improving pediatric residency education, members of the
      R(3)P Project hope to enhance learning, encourage multiple career paths within
      the broad field of pediatrics, and, ultimately, improve patient and family
      outcomes.

PMID- 19088247
TI  - A continuum of competency assessment: the potential for reciprocal use of the
      Accreditation Council for Graduate Medical Education toolbox and the components
      of the American Board of Pediatrics Maintenance-of-Certification Program.
AB  - Reduction of unexplained variation in medical practice and health outcomes is of
      paramount importance, which indicates a need for a continuum of medical learning
      that begins in medical school and continues until the end of a professional
      career. That, in turn, indicates need for continuing assessment of professional
      competence. The American Board of Pediatrics, the American Academy of Pediatrics,
      and the Accreditation Council for Graduate Medical Education are working together
      to develop a common approach to documenting acquisition of competence during
      residency and maintenance of competence thereafter. A common approach will
      eliminate redundancy and make it possible to follow the evolution of professional
      competence over time.

PMID- 19088248
TI  - Looking to the future.
AB  - Participants of the Residency Review and Redesign (R(3)P) Project have created a
      challenging strategic plan for pediatric residency education. In place of a list
      of prescriptions for immediate change, the R(3)P Committee recommends an ongoing
      project of goal-directed change, a quality improvement approach to resident
      education. It argues for changes based on evidence of important education
      outcomes that improve the health of children, adolescents, and young adults.
      Creation and maintenance of a process of ongoing, adaptive change will depend on
      the combined efforts of the Association of Pediatric Program Directors, the
      Association of Medical School Department Chairs, the American Board of
      Pediatrics, the Resident Section of the American Academy of Pediatrics, and the
      Accreditation Council for Graduate Medical Education Review Committee for
      Pediatrics.

PMID- 19088249
TI  - The Residency Review and Redesign in Pediatrics (R3P) Project: roots and
      branches.
AB  - The Residency Review and Redesign in Pediatrics Project was fortunate to be able
      to take advantage of careful thinking by others. In addition to pediatricians, we
      sought advice from medical educators across the spectrum of medicine, especially
      in internal and family medicine. Participants in the project concluded early on
      that top-down "redesign" of pediatric resident education was neither realistic
      nor appropriate. A better and more durable alternative is a formal process by
      which residency education can learn and evolve over time. By committing to that
      model, pediatrics would finally carry out the mandate of the 1978 Task Force on
      Pediatric Education.

PMID- 19088250
TI  - Evaluation of lactation support in the workplace or school environment on 6-month
      breastfeeding outcomes in Yolo County, California.
AB  - Six-month breastfeeding outcomes (almost exclusive breastfeeding, partial
      breastfeeding, and not breastfeeding) were analyzed for 201 infants born to Yolo
      County, California, mothers who returned to work or school. Twenty-two percent of
      workplaces and 17% of schools did not provide a lactation room. Although part- or
      full-time status, knowledge of breastfeeding rules, and support from colleagues
      were independently associated with the outcome, they were not significant in the
      multivariate analysis. In the selected model, maternal age (odds ratio [OR] =
      2.3; 1.3-3.9 for a 10-year difference), college or above versus <or= high school
      education (OR = 9.1; 4.2-19.6), and exclusive breast milk feeding in the hospital
      (OR = 2.1; 1.1-4.0) were associated with better breastfeeding outcomes at 6
      months postpartum. Receipt of discharge gift packs containing formula (OR = 0.5;
      0.3-1.0) was inversely associated with the degree of breastfeeding exclusivity.
      The 2 latter findings underscore the importance of hospitals adhering to specific
      guidelines of the Baby-Friendly Hospital Initiative.

PMID- 19088251
TI  - Adiponectin translation is increased by the PPARgamma agonists pioglitazone and
      omega-3 fatty acids.
AB  - Adiponectin, made exclusively by adipocytes, is a 30-kDa secretory protein
      assembled posttranslationally into low-molecular weight, middle-molecular weight,
      and high-molecular weight homo-oligomers. PPARgamma ligand thiozolidinediones,
      which are widely used in the treatment of type II diabetes, increase adiponectin
      levels. PPARgamma also has several putative ligands that include fatty acid
      derivatives. Overnight treatment of rat adipocytes with pioglitazone,
      docosahexaenoic acid (DHA), or eicosapentaenoic acid (EPA) triggered a twofold
      increase in the synthesis and secretion of HMW adiponectin, and this increase was
      blocked by the addition of PPARgamma inhibitor GW-9662. Inhibition of
      glycosylation using 2,2'-dipyridyl decreased the synthesis of high-molecular
      weight adiponectin by pioglitazone, EPA, and DHA, but there was increased
      secretion of trimeric adiponectin resulting from increased translation. Although
      pioglitazone, DHA, and EPA increased adiponectin synthesis by more than 60%,
      there was no increase in total protein synthesis and no corresponding change in
      adiponectin mRNA expression, indicating the upregulation of translation. We
      examined the possibility of transacting factors in the cytoplasmic extracts from
      adipocytes treated with pioglitazone or DHA. In vitro translation of adiponectin
      mRNA was inhibited by S-100 fraction of control adipocytes and increased by S-100
      extracts from adipocytes treated with pioglitazone or DHA. Consistent with this
      observation, both pioglitazone and DHA treatments increased the association of
      adiponectin mRNA with the heavier polysome fractions. Together, these data
      suggest that pioglitazone and the fish oils DHA or EPA are PPARgamma agonists in
      adipocytes with regard to adiponectin expression, and the predominant mode of
      adiponectin stimulation is via an increase in translation.

PMID- 19088253
TI  - Maternal prenatal undernutrition alters the response of POMC neurons to energy
      status variation in adult male rat offspring.
AB  - Epidemiological studies suggest that maternal undernutrition predisposes the
      offspring to development of energy balance metabolic pathologies in adulthood.
      Using a model of a prenatal maternal 70% food-restricted diet (FR30) in rats, we
      evaluated peripheral parameters involved in nutritional regulation, as well as
      the hypothalamic appetite-regulatory system, in nonfasted and 48-h-fasted adult
      offspring. Despite comparable glycemia in both groups, mild glucose intolerance,
      with a defect in glucose-induced insulin secretion, was observed in FR30 animals.
      They also exhibited hyperleptinemia, despite similar visible fat deposits. Using
      semiquantitative RT-PCR, we observed no basal difference of hypothalamic
      proopiomelanocortin (POMC) and neuropeptide Y (NPY) gene expression, but a
      decrease of the OB-Rb and an increase of insulin receptor mRNA levels, in FR30
      animals. These animals also exhibited basal hypercorticosteronemia and a blunted
      increase of corticosterone in fasted compared with control animals. After
      fasting, FR30 animals showed no marked reduction of POMC mRNA levels or intensity
      of beta-endorphin-immunoreactive fiber projections. By contrast, NPY gene
      expression and immunoreactive fiber intensity increased. FR30 rats also displayed
      subtle alterations of food intake: body weight-related food intake was higher and
      light-dark phase rhythm and refeeding time course were modified after fasting. At
      rest, in the morning, hyperinsulinemia and a striking increase in the number of c
      Fos-containing cells in the arcuate nucleus were observed. About 30% of the c-Fos
      expressing cells were POMC neurons. Our data suggest that maternal undernutrition
      differently programs the long-term appetite-regulatory system of offspring,
      especially the response of POMC neurons to energy status and food intake rhythm.

PMID- 19088252
TI  - Small G proteins as key regulators of pancreatic digestive enzyme secretion.
AB  - Small GTP-binding (G) proteins act as molecular switches to regulate a number of
      cellular processes, including vesicular transport. Emerging evidence indicates
      that small G proteins regulate a number of steps in the secretion of pancreatic
      acinar cells. Diverse small G proteins have been localized at discrete
      compartments along the secretory pathway and particularly on the secretory
      granule. Rab3D, Rab27B, and Rap1 are present on the granule membrane and play a
      role in the steps leading up to exocytosis. Whether the function of these G
      proteins is simply to ensure appropriate targeting or if they are involved as
      regulatory molecules is discussed. Most evidence suggests that Rab3D and Rab27B
      play a role in tethering the secretory granule to its target membrane. Other Rabs
      have been identified on the secretory granule that are associated with different
      steps in the secretory pathway. The Rho family small G proteins RhoA and Rac1
      also regulate secretion through remodeling of the actin cytoskeleton. Possible
      mechanisms for regulation of these G proteins and their effector molecules are
      considered.

PMID- 19088254
TI  - Regulation of human organic anion transporter 1 by ANG II: involvement of protein
      kinase Calpha.
AB  - Human organic anion transporter 1 (hOAT1) belongs to a family of organic anion
      transporters that play critical roles in the body disposition of clinically
      important drugs, including anti-human immunodeficiency virus therapeutics, anti
      tumor drugs, antibiotics, antihypertensives, and anti-inflammatories. hOAT1 is
      abundantly expressed in the kidney. In the current study, we examined the
      regulation of hOAT1 by ANG II in kidney COS-7 cells. ANG II induced a
      concentration- and time-dependent inhibition of hOAT1 transport activity. Such
      inhibition mainly resulted from a decreased cell surface expression without a
      change in total cell expression of the transporter, kinetically revealed as a
      decreased maximal velocity without significant change in Michaelis constant. ANG
      II-induced inhibition of hOAT1 activity could be prevented by treating hOAT1
      expressing cells with staurosporine, a general protein kinase C (PKC) inhibitor.
      To obtain further information on which PKC isoform mediates ANG II regulation of
      hOAT1 activity, cellular distribution of various PKC isoforms was examined in
      cells treated with or without ANG II. We showed that ANG II treatment resulted in
      a significant translocation of PKCalpha from cytosol to membrane, and such
      translocation was blocked by treating hOAT1-expressing cells with Go-6976, a
      PKCalpha-specific inhibitor. We further showed that ANG II-induced inhibition of
      hOAT1 activity and retrieval of hOAT1 from the cell surface could also be
      prevented by treating hOAT1-expressing cells with Go-6976. We concluded that ANG
      II inhibited hOAT1 activity through activation of PKCalpha, which led to the
      redistribution of the transporter from the cell surface to the intracellular
      compartments.

PMID- 19088255
TI  - The role of the G protein-coupled receptor GPR30 in the effects of estrogen in
      ovariectomized mice.
AB  - In vitro studies suggest that the membrane G protein-coupled receptor GPR30 is a
      functional estrogen receptor (ER). The aim of the present study was to determine
      the possible in vivo role of GPR30 as a functional ER primarily for the
      regulation of skeletal parameters, including bone mass and longitudinal bone
      growth, but also for some other well-known estrogen-regulated parameters,
      including uterine weight, thymus weight, and fat mass. Three-month-old
      ovariectomized (OVX) GPR30-deficient mice (GPR30(-/-)) and wild-type (WT) mice
      were treated with either vehicle or increasing doses of estradiol (E(2); 0, 30,
      70, 160, or 830 ng.mouse(-1).day(-1)). Body composition [bone mineral density
      (BMD), fat mass, and lean mass] was analyzed by dual-energy-X ray absorptiometry,
      while the cortical and trabecular bone compartments were analyzed by peripheral
      quantitative computerized tomography. Quantitative histological analyses were
      performed in the distal femur growth plate. Bone marrow cellularity and
      distribution were analyzed using a fluorescence-activated cell sorter. The
      estrogenic responses on most of the investigated parameters, including increase
      in bone mass (total body BMD, spine BMD, trabecular BMD, and cortical bone
      thickness), increase in uterine weight, thymic atrophy, fat mass reduction, and
      increase in bone marrow cellularity, were similar for all of the investigated
      E(2) doses in WT and GPR30(-/-) mice. On the other hand, E(2) treatment reduced
      longitudinal bone growth, reflected by decreased femur length and distal femur
      growth plate height, in the WT mice but not in the GPR30(-/-) mice compared with
      vehicle-treated mice. These in vivo findings demonstrate that GPR30 is not
      required for normal estrogenic responses on several major well-known estrogen
      regulated parameters. In contrast, GPR30 is required for a normal estrogenic
      response in the growth plate.

PMID- 19088256
TI  - Tumor necrosis factor-alpha upregulates 11beta-hydroxysteroid dehydrogenase type
      1 expression by CCAAT/enhancer binding protein-beta in HepG2 cells.
AB  - The enzyme 11beta-hydroxysteroid dehydrogenase type 1 (11beta-HSD1) catalyzes the
      conversion of inactive to active glucocorticoids. 11beta-HSD1 plays a crucial
      role in the pathogenesis of obesity and controls glucocorticoid actions in
      inflammation. Several studies have demonstrated that TNF-alpha increases 11beta
      HSD1 mRNA and activity in various cell models. Here, we demonstrate that mRNA and
      activity of 11beta-HSD1 is increased in liver tissue from transgenic mice
      overexpressing TNF-alpha, indicating that this effect also occurs in vivo. To
      dissect the molecular mechanism of this increase, we investigated basal and TNF
      alpha-induced transcription of the 11beta-HSD1 gene (HSD11B1) in HepG2 cells. We
      found that TNF-alpha acts via p38 MAPK pathway. Transient transfections with
      variable lengths of human HSD11B1 promoter revealed highest activity with or
      without TNF-alpha in the proximal promoter region (-180 to +74). Cotransfection
      with human CCAAT/enhancer binding protein-alpha (C/EBPalpha) and C/EBPbeta-LAP
      expression vectors activated the HSD11B1 promoter with the strongest effect
      within the same region. Gel shift and RNA interference assays revealed the
      involvement of mainly C/EBPalpha, but also C/EBPbeta, in basal and only of
      C/EBPbeta in the TNF-alpha-induced HSD11B1 expression. Chromatin
      immunoprecipitation assay confirmed in vivo the increased abundance of C/EBPbeta
      on the proximal HSD11B1 promoter upon TNF-alpha treatment. In conclusion,
      C/EBPalpha and C/EBPbeta control basal transcription, and TNF-alpha upregulates
      11beta-HSD1, most likely by p38 MAPK-mediated increased binding of C/EBPbeta to
      the human HSD11B1 promoter. To our knowledge, this is the first study showing
      involvement of p38 MAPK in the TNF-alpha-mediated 11beta-HSD1 regulation, and
      that TNF-alpha stimulates enzyme activity in vivo.

PMID- 19088257
TI  - Fenofibrate reduces serum retinol-binding protein-4 by suppressing its expression
      in adipose tissue.
AB  - Fenofibrate is a peroxisome proliferator-activated receptor-alpha (PPARalpha)
      activator that has been clinically used to treat dyslipidemia and insulin
      resistance. To better understand the molecular mechanisms underlying fenofibrate
      action, we investigated whether fenofibrate affects serum levels of retinol
      binding protein-4 (RBP4), an adipocytokine that has recently been shown to link
      obesity and insulin resistance. Fenofibrate treatment significantly decreased
      serum RBP4 levels of dyslipidemic patients, which correlated with reduced body
      weight and increased insulin sensitivity. To elucidate the biochemical mechanisms
      of fenofibrate action, we investigated the effect of fenofibrate on RBP4
      expression in obese rats. Fenofibrate greatly decreased RBP4 mRNA levels in
      adipose tissue but not in the liver, which correlated with decreased serum RBP4
      levels and increased insulin sensitivity in obese rats. Consistent with a direct
      effect on RBP4 expression, fenofibrate treatment significantly reduced the mRNA
      expression levels of RPB4 in 3T3-L1 adipocytes. Together, our results demonstrate
      for the first time that fenofibrate inhibits RPB4 expression in dyslipidemic
      human subjects and suggest that inhibition of RBP4 expression in adipocytes may
      provide a mechanism by which fenofibrate improves insulin sensitivity in
      dyslipidemic patients.

PMID- 19088258
TI  - Just released from the ASAS factory! First steps towards a disease activity score
      for ankylosing spondylitis.

PMID- 19088259
TI  - Abatacept in spondyloarthritis refractory to tumour necrosis factor alpha
      inhibition.

PMID- 19088260
TI  - Subluxing arthropathy: an unusual manifestation of the antisynthetase syndrome.

PMID- 19088261
TI  - Tocilizumab for multirefractory adult-onset Still's disease.

PMID- 19088262
TI  - Lack of association between HLA-G 14 bp insertion/deletion polymorphism and
      response to long-term therapy with methotrexate response in rheumatoid arthritis.

PMID- 19088263
TI  - Comparison of real-time PCR and nested PCR for the detection of Y chromosome
      sequences in the peripheral blood mononuclear cells of patients with systemic
      sclerosis.

PMID- 19088264
TI  - Malignant irreversible intestinal obstruction: the powerful association of
      octreotide to corticosteroids, antiemetics, and analgesics.
AB  - In the case of malignant intestinal obstruction, surgery often carries important
      mortality and morbidity risks, and feasibility is neither realistic nor
      reasonable. A total of 4 clinical cases of intestinal obstruction caused by
      advanced gastrointestinal cancers in their terminal phase are described. The
      association of analgesics, corticosteroids, antiemetics, and octreotide was
      effective to relieve symptoms of intestinal obstruction for the remaining
      lifetime. The insertion of a nasogastric tube was avoided in 3 of 4 cases. Death
      occurred 51, 56, and 64 days after clinical and radiological diagnosis of
      irreversible intestinal obstruction. This combination of drugs appears very
      powerful and well tolerated. The relatively long survival that was observed
      should encourage future studies of longer half-life somatostatin analogues with
      no need of continuous infusion or multiple daily injections.

PMID- 19088266
TI  - Sex-related differences in the expression of mfGSTA2, a novel GST identified in
      cynomolgus monkey (Macaca fascicularis).
AB  - Glutathione S-transferase (GST) is one of the most important phase II drug
      metabolizing enzymes, catalyzing the conjugation of electrophilic substrates to
      glutathione. Unlike in humans, a surprisingly limited number of GST genes have
      been identified in monkeys. The identification of additional GST genes in this
      model system would prove to be advantageous, because monkeys remain an important
      predictor of drug effects and toxicities in humans during preclinical studies. In
      this study, we report the identification and characterization of the following
      six cDNAs in cynomolgus monkeys: mfGSTA1, mfGSTA2, mfGSTM5, mfMGST1, mfGSTO1, and
      mfGSTZ1. These cDNAs encode GSTs highly homologous (approximately 95%) to human
      GST cDNAs. Among these, the mfGSTA1, mfGSTM5, mfMGST1, mfGSTO1, and mfGSTZ1 cDNAs
      correspond to a single human GST counterpart, whereas the mfGSTA2 cDNA is highly
      similar to human GSTA1 and GSTA2 cDNAs. An analysis of tissue samples indicates
      that these GST genes are predominantly expressed in the liver along with some
      extrahepatic expression as determined by real-time reverse transcriptase
      polymerase chain reaction. It is interesting to note that mfGSTA2 is
      significantly differentially expressed between males and females in the jejunum,
      where a striking 8-fold higher expression level is observed in males. These
      results suggest that a potential sex difference in the metabolism of drugs may be
      mediated by mfGSTA2. This also provides a basis for the investigation of sex
      dependent drug metabolism in monkeys.

PMID- 19088265
TI  - Hepatic flavin-containing monooxygenase gene regulation in different mouse
      inflammation models.
AB  - The objective of the study was to investigate the regulation of hepatic flavin
      containing monooxygenases (Fmo) Fmo1, Fmo3, Fmo4, and Fmo5 in three different
      mouse models of inflammation, including treatment with Citrobacter rodentium,
      lipopolysaccharide (LPS), and dextran sulfate sodium (DSS). Quantitative real
      time reverse transcription-polymerase chain reaction (RT-PCR) was used to
      evaluate the steady-state mRNA levels for the various Fmo isoforms in these mouse
      models of inflammation during different treatment time courses. Fmo3 mRNA was
      most significantly down-regulated in C. rodentium-treated female mice. Fmo1,
      Fmo3, and Fmo5 mRNAs were also found to be down-regulated in LPS models of
      inflammation. The significant down-regulation of hepatic FMO3 protein during C.
      rodentium treatment was confirmed with Western blot analysis of liver microsomes
      from treated animals. Toll-like receptor (TLR) 4 is known to be responsible for
      LPS signaling in association with several proteins. To investigate whether TLR4
      was responsible for regulation of Fmo genes in both LPS and C. rodentium animal
      models, Fmo mRNA levels in female wild-type (C3H/HeOuJ) and TLR4 mutant (C3H/HeJ)
      mice were compared in both inflammatory models by real-time RT-PCR. The results
      showed that Fmo3 down-regulation during C. rodentium infection is independent of
      TLR4. Whereas TLR4 is likely to play only a partial role in Fmo1 gene regulation
      in LPS-treated animals, our results show that the down-regulation of Fmo3 and
      Fmo5 in this model is TLR4-dependent. Unlike cytochrome P450 regulation measured
      in the same mouse strains, Fmo3 expression was largely refractory to down
      regulation in the DSS model of inflammatory colitis.

PMID- 19088267
TI  - An inhibitory metabolite leads to dose- and time-dependent pharmacokinetics of
      (R)-N-{1-[3-(4-ethoxy-phenyl)-4-oxo-3,4-dihydro-pyrido[2,3-d]pyrimidin-2-yl]
      ethyl}-N-pyridin-3-yl-methyl-2-(4-trifluoromethoxy-phenyl)-acetamide (AMG 487) in
      human subjects after multiple dosing.
AB  - (R)-N-{1-[3-(4-Ethoxy-phenyl)-4-oxo-3,4-dihydro-pyrido[2,3-d]-pyrimidin-2-yl]
      ethyl}-N-pyridin-3-yl-methyl-2-(4-trifluoromethoxyphenyl)-acetamide (AMG 487) is
      a potent and selective orally bioavailable chemokine (C-X-C motif) receptor 3
      (CXCR3) antagonist that displays dose- and time-dependent pharmacokinetics in
      human subjects after multiple oral dosing. Although AMG 487 exhibited linear
      pharmacokinetics on both days 1 and 7 at the 25-mg dose, dose- and time-dependent
      kinetics were evident at the two higher doses. Nonlinear kinetics were more
      pronounced after multiple dosing. Area under the plasma concentration-time curve
      from 0 to 24 h [AUC((0-24 h))] increased 96-fold with a 10-fold increase in dose
      on day 7 compared with a 28-fold increase in AUC((0-24 h)) on day 1. These
      changes were correlated with time- and dose-dependent decreases in the metabolite
      to parent plasma concentrations, suggesting that these changes result from a
      decrease in the oral clearance (CL) of AMG 487 (e.g., intestinal/hepatic first
      pass metabolism and systemic CL). The biotransformation of AMG 487 is dependent
      on CYP3A and results in the formation of two primary metabolites, a pyridyl N
      oxide AMG 487 (M1) and an O-deethylated AMG 487 (M2). One of these metabolites,
      M2, undergoes further metabolism by CYP3A. M2 has also been demonstrated to
      inhibit CYP3A in a competitive (K(i)=0.75 microM) manner as well as via mechanism
      based inhibition (unbound K(I)=1.4 microM, k(inact)=0.041 min(-1)). Data from
      this study implicate M2-mediated CYP3A mechanism-based inhibition as the proximal
      cause for the time-dependent pharmacokinetics of AMG 487. However, the sequential
      metabolism of M2, nonlinear AMG 487 pharmacokinetics, and the inability to
      accurately determine the role of intestinal AMG 487 metabolism complicates the
      correlation between M2 plasma concentrations and the time-dependent AMG 487
      pharmacokinetic changes.

PMID- 19088268
TI  - Adenoviruses: update on structure and function.
AB  - Adenoviruses have been studied intensively for over 50 years as models of virus
      cell interactions and latterly as gene vectors. With the advent of more
      sophisticated structural analysis techniques the disposition of most of the 13
      structural proteins have been defined to a reasonable level. This review seeks to
      describe the functional properties of these proteins and shows that they all have
      a part to play in deciding the outcome of an infection and act at every level of
      the virus's path through the host cell. They are primarily involved in the
      induction of the different arms of the immune system and a better understanding
      of their overall properties should lead to more effective ways of combating virus
      infections.

PMID- 19088269
TI  - In vivo imaging of murid herpesvirus-4 infection.
AB  - Luciferase-based imaging allows a global view of microbial pathogenesis. We
      applied this technique to gammaherpesvirus infection by inserting a luciferase
      expression cassette into the genome of murine herpesvirus-4 (MuHV-4). The
      recombinant virus strongly expressed luciferase in lytically infected cells
      without significant attenuation. We used it to compare different routes of virus
      inoculation. After intranasal infection of anaesthetized mice, luciferase was
      expressed in the nose and lungs for 7-10 days and in lymphoid tissue, most
      consistently the superficial cervical lymph nodes, for up to 30 days.
      Gastrointestinal infection was not observed. Intraperitoneal infection was very
      different to intranasal, with strong luciferase expression in the liver, kidneys,
      intestines, reproductive tract and spleen, but none in the nose or lungs. The
      nose has not previously been identified as a site of MuHV-4 infection. After
      intranasal infection of non-anaesthetized mice, it was the only site of non
      lymphoid luciferase expression. Nevertheless, lymphoid colonization and
      persistence were still established, even at low inoculation doses. In contrast,
      virus delivered orally was very poorly infectious. Inoculation route therefore
      had a major impact on pathogenesis. Low dose intranasal infection without
      anaesthesia seems most likely to mimic natural transmission, and may therefore be
      particularly informative about normal viral gene functions.

PMID- 19088270
TI  - Murine cytomegalovirus displays selective infection of cells within hours after
      systemic administration.
AB  - A distinctive feature of the cytomegaloviruses is their wide tissue tropism,
      demonstrated by the infection of many organs and cell types in an active
      infection. However, in experimental models of systemic infection, the earliest
      stages of infection are not well characterized, and it is unclear whether only
      certain cells are initially infected. Using a recombinant murine cytomegalovirus
      (MCMV) expressing green fluorescent protein (GFP), we tracked viral infection
      after systemic administration via intraperitoneal injection and showed that
      specific cells are infected within the first hours. We provide evidence that MCMV
      traffics as free virus from the peritoneal cavity into the mediastinal
      lymphatics, providing access to the bloodstream. We demonstrate that MCMV
      productively infected CD169(+) subcapsular sinus macrophages in the mediastinal
      lymph nodes, ER-TR7(+) CD29(+) reticular fibroblasts in the spleen and
      hepatocytes. Infection in the spleen followed a distinctive pattern, beginning in
      the marginal zone at 6 h and spreading into the red pulp by 17 h. By 48 h after
      infection, there was widespread infection in the spleen and liver with
      degeneration of infected cells. In addition, infected dendritic cells appeared in
      the white pulp of the spleen at 48 h post-infection. On the other hand, cowpox
      virus showed a different pattern of infectivity in the spleen and liver. Thus,
      early MCMV infection produces a distinct pattern of infection of selective cells.

PMID- 19088271
TI  - Partial molecular characterization of alphaherpesviruses isolated from tropical
      bats.
AB  - Herpesviruses have previously been isolated from African and South-American bats.
      Recently, herpesviruses detected from European insectivorous bats (family
      Vespertilionidae) were classified molecularly as betaherpesviruses and
      gammaherpesviruses. In the current study, we performed PCR analyses targeting the
      UL30 catalytic subunit region of the DNA polymerase gene of the African and South
      American herpesviruses and new Malagasy and Cambodian herpesviruses isolated from
      bats, especially frugivorous bats from the families Pteropodidae and
      Phyllostomidae. The sequences obtained from the amplified products indicated that
      these isolates belonged to the genus Simplexvirus of the subfamily
      Alphaherpesvirinae. These results extend the taxonomic range of bat herpesviruses
      with the description of four members in the subfamily Alphaherpesvirinae.
      Furthermore, these data confirm and extend the geographical distribution of
      herpesvirus in bats to three more continents (Africa, South America and Asia) and
      indicate the presence of these viruses in frugivorous bats of the families
      Pteropodidae and Phyllostomidae.

PMID- 19088273
TI  - Analysis of the subcellular trafficking properties of murine cytomegalovirus M78,
      a 7 transmembrane receptor homologue.
AB  - Murine cytomegalovirus (MCMV) M78 is a member of the betaherpesvirus 'UL78
      family' of seven transmembrane receptor (7TMR) genes. Previous studies of M78 and
      its counterpart in rat cytomegalovirus (RCMV) have suggested that these genes are
      required for efficient cell-cell spread of their respective viruses in tissue
      culture and demonstrated that gene knockout viruses are significantly attenuated
      for replication in vivo. However, in comparison with other CMV 7TMRs, relatively
      little is known about the basic biochemical properties and subcellular
      trafficking of the UL78 family members. We have characterized MCMV M78 in both
      transiently transfected and MCMV-infected cells to determine whether M78 exhibits
      features in common with cellular 7TMR. We obtained preliminary evidence that M78
      formed dimers, a property that has been reported for several cellular 7TMR. M78
      traffics to the cell surface, but was rapidly and constitutively endocytosed.
      Antibody feeding experiments demonstrated co-localization of M78 with markers for
      both the clathrin-dependent and lipid raft/caveolae-mediated internalization
      pathways. In MCMV-infected cells, the subcellular localization of M78 was
      modified during the course of infection, which may be related to the
      incorporation of M78 into the virion envelope during the course of virion
      maturation.

PMID- 19088272
TI  - CD81 is dispensable for hepatitis C virus cell-to-cell transmission in hepatoma
      cells.
AB  - Hepatitis C virus (HCV) infects cells by the direct uptake of cell-free virus
      following virus engagement with specific cell receptors such as CD81. Recent data
      have shown that HCV is also capable of direct cell-to-cell transmission, although
      the role of CD81 in this process is disputed. Here, we generated cell culture
      infectious strain JFH1 HCV (HCVcc) genomes carrying an alanine substitution of E2
      residues W529 or D535 that are critical for binding to CD81 and infectivity. Co
      cultivation of these cells with naive cells expressing enhanced green fluorescent
      protein (EGFP) resulted in a small number of cells co-expressing both EGFP and
      HCV NS5A, showing that the HCVcc mutants are capable of cell-to-cell spread. In
      contrast, no cell-to-cell transmission from JFH1(DeltaE1E2)-transfected cells
      occurred, indicating that the HCV glycoproteins are essential for this process.
      The frequency of cell-to-cell transmission of JFH1(W529A) was unaffected by the
      presence of neutralizing antibodies that inhibit E2-CD81 interactions. By using
      cell lines that expressed little or no CD81 and that were refractive to infection
      with cell-free virus, we showed that the occurrence of viral cell-to-cell
      transmission is not influenced by the levels of CD81 on either donor or recipient
      cells. Thus, our results show that CD81 plays no role in the cell-to-cell spread
      of HCVcc and that this mode of transmission is shielded from neutralizing
      antibodies. These data suggest that therapeutic interventions targeting the entry
      of cell-free HCV may not be sufficient in controlling an ongoing chronic
      infection, but need to be complemented by additional strategies aimed at
      disrupting direct cell-to-cell viral transmission.

PMID- 19088274
TI  - Upstream-binding factor is sequestered into herpes simplex virus type 1
      replication compartments.
AB  - Previous reports have shown that adenovirus recruits nucleolar protein upstream
      binding factor (UBF) into adenovirus DNA replication centres. Here, we report
      that despite having a different mode of viral DNA replication, herpes simplex
      virus type 1 (HSV-1) also recruits UBF into viral DNA replication centres.
      Moreover, as with adenovirus, enhanced green fluorescent protein-tagged fusion
      proteins of UBF inhibit viral DNA replication. We propose that UBF is recruited
      to the replication compartments to aid replication of HSV-1 DNA. In addition,
      this is a further example of the role of nucleolar components in viral life
      cycles.

PMID- 19088275
TI  - Herpes simplex virus infection is sensed by both Toll-like receptors and retinoic
      acid-inducible gene- like receptors, which synergize to induce type I interferon
      production.
AB  - The innate antiviral response is initiated by pattern recognition receptors,
      which recognize viral pathogen-associated molecular patterns. Here we show that
      retinoic acid-inducible gene (RIG)-I-like receptors (RLRs) in cooperation with
      Toll-like receptor (TLR) 9 is required for expression of type I interferons
      (IFNs) after infection with herpes simplex virus (HSV). Our work also identified
      RNase L as a critical component in IFN induction. Moreover, we found that TLR9
      and RLRs activate distinct, as well as overlapping, intracellular signalling
      pathways. Thus, RLRs are important for recognition of HSV infection, and
      cooperate with the Toll pathway to induce an antiviral response.

PMID- 19088276
TI  - Cytokine production by human herpesvirus 8-infected dendritic cells.
AB  - We have shown previously that human herpesvirus 8 (HHV-8)-infected dendritic
      cells (DCs) undergo incomplete maturation and have a defective antigen-presenting
      function. Here, we examined the effects of HHV-8 infection on cytokine
      production, which is critical to the function of DCs. We detected expression of
      interleukin (IL)-6, tumour necrosis factor (TNF)-alpha, macrophage inflammatory
      protein (MIP)-1alpha, MIP-1beta, RANTES and IL-12p40 from 2 to 6 h post
      infection, and these peaked by 15-24 h. Expression of these factors decreased 24
      48 h post-infection, with the exception of TNF-alpha which remained high
      throughout the entire 72 h. Interestingly, while IL-12p40 expression increased
      post-infection, bioactive IL-12p70 was not detected in the supernatants. These
      results suggest an intentional skewing of cytokine production in HHV-8-infected
      DCs towards induction of a Th2 response.

PMID- 19088277
TI  - Adenovirus DNA polymerase is recognized by human CD8+ T cells.
AB  - Donor lymphocytes have potential as a treatment for adenovirus (Ad) disease in
      haematopoietic stem cell transplant (SCT) recipients, but better understanding of
      Ad-specific T-cell responses is required. Most healthy adults exhibit memory T
      cell responses to hexon, a capsid protein synthesized late after infection.
      However, since the Ad E3-19k downregulates major histocompatibility complex (MHC)
      class I molecules, cytotoxic T cells (CTLs) targeted to early viral proteins may
      be more effective in eliminating Ad-infected cells in vivo. Here we show that Ad
      specific CTLs recognize the early region 2 proteins DNA polymerase (Pol) and DNA
      binding protein (DBP). Firstly, memory Ad-specific CD8(+) T cells were amplified
      from healthy donors by in vitro stimulation with Ad-infected dendritic cells and
      found to exhibit MHC-restricted cytotoxicity to targets expressing Pol and DBP.
      Secondly, gamma interferon responses to HLA A2-binding motif peptides from Pol
      and DBP were directly detected in peripheral blood mononuclear cells (PBMCs) from
      a recently infected normal donor. Peptide-specific CTLs generated to Pol and DBP
      epitopes were confirmed to exhibit HLA A2-restricted killing of targets
      expressing Pol or DBP. Lastly, Pol-epitope-specific T cells were detected at
      similar or higher frequencies than hexon and DBP in three of three SCT recipients
      recovering from invasive Ad disease. Pol epitopes were well conserved among
      different Ad serotypes. Therefore, Pol is a promising target for immunotherapy of
      Ad disease.

PMID- 19088278
TI  - Adenovirus type 5 E4 Orf3 protein targets promyelocytic leukaemia (PML) protein
      nuclear domains for disruption via a sequence in PML isoform II that is predicted
      as a protein interaction site by bioinformatic analysis.
AB  - Human adenovirus type 5 infection causes the disruption of structures in the cell
      nucleus termed promyelocytic leukaemia (PML) protein nuclear domains or ND10,
      which contain the PML protein as a critical component. This disruption is
      achieved through the action of the viral E4 Orf3 protein, which forms track-like
      nuclear structures that associate with the PML protein. This association is
      mediated by a direct interaction of Orf3 with a specific PML isoform, PMLII. We
      show here that the Orf3 interaction properties of PMLII are conferred by a 40 aa
      residue segment of the unique C-terminal domain of the protein. This segment was
      sufficient to confer interaction on a heterologous protein. The analysis was
      informed by prior application of a bioinformatic tool for the prediction of
      potential protein interaction sites within unstructured protein sequences
      (predictors of naturally disordered region analysis; PONDR). This tool predicted
      three potential molecular recognition elements (MoRE) within the C-terminal
      domain of PMLII, one of which was found to form the core of the Orf3 interaction
      site, thus demonstrating the utility of this approach. The sequence of the mapped
      Orf3-binding site on PML protein was found to be relatively poorly conserved
      across other species; however, the overall organization of MoREs within
      unstructured sequence was retained, suggesting the potential for conservation of
      functional interactions.

PMID- 19088279
TI  - Yemen and Vietnam capripoxviruses demonstrate a distinct host preference for
      goats compared with sheep.
AB  - Sheeppox and goatpox are caused by viruses that are members of the genus
      Capripoxvirus, and globally result in significant production losses. To improve
      the understanding of disease pathogenesis and evaluate host species preferences,
      sheep and goats were inoculated either with a capripoxvirus isolate from Yemen or
      from a recent outbreak in Vietnam. Blood, swabs and tissues were collected at
      various time points following experimental challenge and assessed for viral DNA
      content using real-time PCR and infectivity using virus isolation. The Yemen
      isolate was considerably more pathogenic in goats with 100 % mortality and
      morbidity compared with sheep with 0 % mortality and 100 % morbidity. The Vietnam
      isolate was also more pathogenic in goats with 100 % morbidity and an estimated
      33 % mortality rate compared with mild morbidity and a 0 % mortality rate in
      sheep. Higher viral titres were observed in nasal, oral and conjunctival swabs
      from goats inoculated with either the Yemen or Vietnam isolate compared with
      those collected from sheep. Although the highest viral titres were detected in
      primary and secondary skin lesions in sheep and goats, the severity of clinical
      disease observed in each species varied according to the inoculum used. Whereas
      both the Yemen and Vietnam isolates clearly caused more severe disease in goats,
      the Yemen isolate was also moderately pathogenic in sheep. The Vietnam isolate,
      in contrast, caused only very mild disease in sheep. Limited DNA sequencing
      revealed ORF 074 of the Vietnam isolate to be identical to that of several
      goatpox virus isolates from China, suggesting a possible Chinese origin.

PMID- 19088281
TI  - Persistence of the hepatitis B virus covalently closed circular DNA in HepaRG
      human hepatocyte-like cells.
AB  - The recently described hepatic cell line HepaRG is the sole hepatoma cell line
      susceptible to hepatitis B virus (HBV) infection. It provides a unique tool for
      investigating some unresolved issues of the virus' biology, particularly the
      formation of the viral mini-chromosome believed to be responsible for the
      persistence of infection. In this study, we characterized the main features of
      HBV infection: it is restricted to a subpopulation of differentiated hepatocyte
      like cells that express albumin as a functional marker and represents around 10 %
      of all differentiated HepaRG cells. Infection may persist for more than 100 days
      in cells maintained at the differentiated state. Even though infected cells
      continued to produce infectious viral particles, very limited or no spreading of
      infection was observed. Low genetic variation was also observed in the viral DNA
      from viruses found in the supernatant of infected cells, although this cannot
      explain the lack of reinfection. HBV infection of HepaRG cells appears to be a
      very slow process: viral replication starts at around day 8 post-infection and
      reaches a maximum at day 13. Analysis of viral DNA showed slow and inefficient
      conversion of the input relaxed circular DNA into covalently closed circular
      (CCC) DNA, but no further amplification. Continuous lamivudine treatment
      inhibited viral replication, but neither prevented viral infection nor initial
      formation of CCC DNA. In conclusion, HBV infection in differentiated HepaRG cells
      is characterized by long-term persistence without a key feature of
      hepadnaviruses, the so-called 'CCC DNA amplification' described in the duck
      hepatitis B model.

PMID- 19088280
TI  - Hepatitis B virus (HBV)-specific short hairpin RNA is capable of reducing the
      formation of HBV covalently closed circular (CCC) DNA but has no effect on
      established CCC DNA in vitro.
AB  - Hepatitis B virus (HBV) covalently closed circular (CCC) DNA is the source of HBV
      transcripts and persistence in chronically infected patients. The novel aspect of
      this study was to determine the effect of RNA interference (RNAi) on HBV CCC DNA
      when administered prior to establishment of HBV replication or during chronic HBV
      infection. HBV replication was initiated in HepG2 cells by transduction with HBV
      baculovirus. Subculture of HBV-expressing HepG2 cells at 10 days post
      transduction generates a system in which HBV replication is ongoing and HBV is
      expressed largely from CCC DNA, thus simulating chronic HBV infection. HepG2
      cells were transduced with short hairpin RNA (shRNA)-expressing baculovirus prior
      to initiation of HBV replication or during chronic HBV replication, and the
      levels of HBV RNA, HBV surface antigens (HBsAg) and replicative intermediates
      (RI), extracellular (EC) and CCC DNA species were measured. HBsAg, HBV RNA and
      DNA levels were markedly reduced until day 8 whether cells were transduced with
      shRNA prior to or during a chronic infection; however, the CCC DNA species were
      only affected when shRNA was administered prior to initiation of infection. We
      conclude that RNAi may have a therapeutic value for controlling HBV replication
      at the level of RI and EC DNA and for reducing establishment of CCC DNA during
      HBV infection. Our data support previous findings demonstrating the stability of
      HBV CCC DNA following antiviral therapy. This study also reports the development
      of a novel HBV baculovirus subculture system that can be used to evaluate
      antiviral effects on chronic HBV replication.

PMID- 19088282
TI  - Serological relationship between cutaneous human papillomavirus types 5, 8 and
      92.
AB  - Evidence of a possible association of cutaneous human papillomavirus (HPV) types,
      especially members of the genus Betapapillomavirus, and the development of non
      melanoma skin cancer (NMSC) is accumulating. Vaccination with virus-like
      particles (VLPs) consisting of self-assembled L1, the major capsid protein, has
      been introduced to control anogenital HPV infection. This study examined the
      serological relationship between betapapillomavirus (beta-PV) types 5 and 8 and
      the new type HPV-92, which has recently been isolated from a basal cell carcinoma
      containing a high number of viral genomes. Following expression by recombinant
      baculoviruses, the L1 protein of HPV-92 self-assembled into VLPs that elicited
      high-titre antibodies after immunization, similar to VLPs from HPV-5 and -8.
      Haemagglutination inhibition (HAI) assays were used as a surrogate method for the
      detection of virion-neutralizing antibodies, which correlates with protection
      from infection. Antisera raised against HPV-5 and -8 VLPs displayed HAI activity
      not only against the homologous type, but also against heterologous HPV types 5,
      8 and 92, whereas HAI activity of antisera against HPV-92 VLP was restricted to
      the homologous type. The results of neutralization assays using HPV-5
      pseudovirions were consistent with those from HAI assays. Cross-neutralizing
      immune responses by VLP vaccination against heterologous HPV types may provide
      broader protection against the multiplicity of HPV types detected in NMSC. If a
      close link to HPV infection can be conclusively established, these results may
      provide a basis for further evaluation of VLPs of beta-PVs as candidates for a
      prophylactic skin-type HPV vaccine, aimed at reducing the incidence of NMSC.

PMID- 19088283
TI  - Distribution patterns of BK polyomavirus (BKV) subtypes and subgroups in
      American, European and Asian populations suggest co-migration of BKV and the
      human race.
AB  - BK polyomavirus (BKV) is ubiquitous in the human population, infecting children
      asymptomatically and then persisting in the kidney. Based on serological and
      genotyping methods, BKV isolates worldwide are classified into four subtypes (I
      IV), with subtype I prevalent throughout the world, subtype IV prevalent in Asia
      and part of Europe, and subtypes II and III rare throughout the world.
      Phylogenetic analyses of complete genome sequences have identified several
      geographically distinct subgroups of subtypes I and IV. To explain how the
      geographical distribution patterns of BKV subtypes and subgroups were formed,
      this study hypothesized that BKV co-migrated with human populations (the co
      migration hypothesis), and examined this hypothesis by comparing the BKV subtype
      and subgroup profiles among two American populations in North-east USA and
      southern California, two European populations in Finland and Ireland/England, and
      two Asian populations in Japan and China (both American populations were composed
      mainly of European Americans). The frequency of subtype I was always the highest
      throughout the populations, but that of subtype IV was variable among
      populations. A subgroup of subtype I (I/b-2) was detected primarily in all of the
      European and American populations, whereas subgroup I/c was predominant in the
      Asian populations (the observed difference was statistically significant).
      Additionally, all of the five fully sequenced subtype IV isolates from the
      American and European populations belonged to subgroup IV/c-2, whereas all
      subtype IV isolates from the Asian populations belonged to the other subgroups.
      Collectively, the current findings provide support for the co-migration
      hypothesis.

PMID- 19088284
TI  - Variants of open reading frame Bm126 in wild-type Bombyx mori
      nucleopolyhedrovirus isolates exhibit functional differences.
AB  - The open reading frame (ORF) 126 (Bm126) of Bombyx mori nucleopolyhedrovirus
      (BmNPV) is a homologue of Ac150 and belongs to the baculovirus 11K protein
      family. Bm126 was amplified from BmNPVs isolated from five different regions of
      China. Sequence analysis showed that the isolates had two different subtypes of
      Bm126, Bm126-SX and Bm126-GD, and both were different from that of the BmNPV T3
      isolate. All of the BM126 ORFs contained a hydrophobic N terminus and a C6 motif
      at their C terminus, but the sequence between the N terminus and C6 motif varied
      in each isolate. The function of Bm126 was studied using bacmid BmBacJS13 derived
      from a BmNPV containing Bm126-SX. A 3' rapid amplification of cDNA ends showed
      that the transcript of Bm126 was first detected at 6 h post-infection. A Bm126
      knockout bacmid was constructed in which the majority of the coding region of
      Bm126 was deleted. Subsequently, the gene was repaired with Bm126-SX or Bm126-GD
      and tested for infectivity. The deletion of Bm126 had no obvious effect on the
      budded virus growth curve and the mean lethal dose of the occlusion bodies (OBs);
      however, the mean survival time of the larvae infected with Bm126-null virus was
      significantly delayed compared with that of the control virus. The delay was
      rescued by repairing the deletion with Bm126-SX but not with Bm126-GD. In
      addition, the virus repaired with Bm126-GD showed a significant increase in OB
      yield, both in vitro and in vivo.

PMID- 19088285
TI  - Bombyx mori nucleopolyhedrovirus ORF9 is a gene involved in the budded virus
      production and infectivity.
AB  - The ORF9 of Bombyx mori nucleopolyhedrovirus (BmNPV) (Bm9) is conserved in all
      completely sequenced lepidopteran nucleopolyhedroviruses. RT-PCR analysis
      demonstrated that Bm9 is an early and late transcribed gene that is initiated at
      3 h post-infection, and immunofluorescence microscopy showed that Bm9 is
      localized mainly in the cytoplasm of infected cells. To determine the role of Bm9
      during virus infection, Bm9 was knocked out by recombination in a BmNPV genome
      propagated as a bacmid in Escherichia coli. The budded virus (BV) production of
      Bm9-deleted bacmids was reduced more than 10-fold compared with wild-type (wt)
      bacmid; however, the kinetics of viral DNA replication were unaffected. The
      defect in BV production was recovered by the Bm9 rescue bacmid. In addition,
      electron microscope observations revealed that polyhedra formation was not
      affected by the deletion of Bm9. Bioassays showed that the Bm9-deleted bacmid
      took approximately 14-22 h longer to kill fifth instar B. mori larvae than wt
      bacmid, and the LD(50) was about 15 times higher than that of the wt bacmid. In
      conclusion, Bm9 is an important but not essential factor in virus production and
      infectivity in vivo and in vitro.

PMID- 19088286
TI  - N-linked glycans located in the pro-region of Bombyx mori nucleopolyhedrovirus V
      CATH are essential for the proper folding of V-CATH and V-CHIA.
AB  - Post-mortem host degradation by infection of Bombyx mori nucleopolyhedrovirus
      (BmNPV) requires the synergistic activation of two virus-encoded genes, cathepsin
      (v-cath) and chitinase (v-chiA). Previous studies have suggested that V-CHIA is
      essential for the proper folding of the nascent V-CATH polypeptide in the
      endoplasmic reticulum, and that the putative V-CHIA-V-CATH interaction might be
      mediated by N-linked glycans of V-CATH. Sequence analysis shows that BmNPV V-CATH
      includes three consensus N-linked glycosylation sites (asparagine 38, 65 and
      158). To clarify the role of N-linked glycans of V-CATH in its biological
      activity, we generated three recombinant BmNPVs expressing mutant V-CATHs, and
      found that the two residues, asparagine 38 and 65, which are localized in the pro
      region of V-CATH, are the glycosylation sites of BmNPV V-CATH. Western blot
      analysis also showed that removal of N-linked glycans from BmNPV V-CATH resulted
      in production of the insoluble forms of V-CATH and V-CHIA. These results
      demonstrate that N-linked glycans located in the pro-region of BmNPV V-CATH are
      essential for the proper folding of V-CATH and V-CHIA.

PMID- 19088287
TI  - Inhibition of mRNA export and dimerization of interferon regulatory factor 3 by
      Theiler's virus leader protein.
AB  - Theiler's murine encephalomyelitis virus (TMEV or Theiler's virus) is a
      neurotropic picornavirus that can persist lifelong in the central nervous system
      of infected mice, causing a chronic inflammatory demyelinating disease. The
      leader (L) protein of the virus is an important determinant of viral persistence
      and has been shown to inhibit transcription of type I interferon (IFN) genes and
      to cause nucleocytoplasmic redistribution of host proteins. In this study, it was
      shown that expression of the L protein shuts off synthesis of the reporter
      proteins green fluorescent protein and firefly luciferase, suggesting that it
      induces a global shut-off of host protein expression. The L protein did not
      inhibit transcription or translation of the reporter genes, but blocked cellular
      mRNA export from the nucleus. This activity correlated with the phosphorylation
      of nucleoporin 98 (Nup98), an essential component of the nuclear pore complex. In
      contrast, the data confirmed that the L protein inhibited IFN expression at the
      transcriptional level, and showed that transcription of other chemokine or
      cytokine genes was affected by the L protein. This transcriptional inhibition
      correlated with inhibition of interferon regulatory factor 3 (IRF-3)
      dimerization. Whether inhibition of IRF-3 dimerization and dysfunction of the
      nuclear pore complex are related phenomena remains an open question. In vivo, IFN
      antagonism appears to be an important role of the L protein early in infection,
      as a virus bearing a mutation in the zinc finger of the L protein replicated as
      efficiently as the wild-type virus in type I IFN receptor-deficient mice, but had
      impaired fitness in IFN-competent mice.

PMID- 19088288
TI  - Efficient infection of buffalo rat liver-resistant cells by encephalomyocarditis
      virus requires binding to cell surface sialic acids.
AB  - In contrast to the production of virus and cell lysis seen in baby hamster kidney
      cells (BHK-21) infected with the strain 1086C of encephalomyocarditis virus
      (EMCV), in buffalo rat liver cells (BRL) neither virus replication nor cytopathic
      effects were observed. After 29 passages in BRL cells, each alternating with
      boosts of the recovered virus in BHK-21 cells, the virus acquired the ability to
      replicate effectively in BRL cells, attaining virus titres comparable to those in
      BHK-21 cells and producing complete cell destruction. The binding of virus on BRL
      cells was increased after adaptation and was similar to that observed on BHK-21
      cells. Treatment of BRL cells with sialidase resulted in an 87 % reduction in
      virus binding and inhibition of infection. Sequence analyses revealed three
      mutations in the VP1 amino acid sequence of the adapted virus at positions 49
      (Lys-->Glu), 142 (Leu-->Phe) and 180 (Ile-->Ala). The residue 49 is exposed at
      the surface of the capsid and is known to be part of a neutralization epitope.
      These results suggest that the adaptation of EMCV to BRL cells may have occurred
      through a mutation in a neutralizing site that confers to the virus a capacity to
      interact with cell surface sialic acid residues. Taken together, these data
      suggest a link between virus neutralization site, receptor binding and cell
      permissivity to infection.

PMID- 19088289
TI  - Integrin alphaVbeta6 is a high-affinity receptor for coxsackievirus A9.
AB  - Coxsackievirus A9 (CAV9), a member of the genus Enterovirus in the family
      Picornaviridae, possesses an integrin-binding arginine-glycine-aspartic acid
      (RGD) motif in the C terminus of VP1 capsid protein. CAV9 has been shown to
      utilize integrins alphaVbeta3 and alphaVbeta6 as primary receptors for cell
      attachment. While CAV9 RGD-mutants (RGE and RGDdel) are capable of infecting
      rhabdomyosarcoma (RD) cell line, they grow very poorly in an epithelial lung
      carcinoma cell line (A549). In this study, the relationships between CAV9
      infectivity in A549 and RD cells, receptor expression and integrin binding were
      analysed. A549 cells were shown to express both integrins alphaVbeta3 and
      alphaVbeta6, whereas alphaVbeta6 expression was not detected on the RD cells.
      Native CAV9 but not RGE and RGDdel mutants bound efficiently to immobilized
      alphaVbeta3 and alphaVbeta6. Adhesion of CAV9 but not RGE/RGDdel to A549 cells
      was also significantly higher than to RD cells. In contrast, no affinity or
      adhesion of bacterially produced VP1 proteins to the integrins or to the cells
      was detected. Function-blocking antibodies against alphaV-integrins blocked CAV9
      but not CAV9-RGDdel infectivity, indicating that the viruses use different
      internalization routes; this may explain the differential infection kinetics of
      CAV9 and RGDdel. In an affinity assay, soluble alphaVbeta6, but not alphaVbeta3,
      bound to immobilized CAV9. Similarly, only soluble alphaVbeta6 blocked virus
      infectivity. These data suggest that CAV9 binding to alphaVbeta6 is a high
      affinity interaction, which may indicate its importance in clinical infections;
      this remains to be determined.

PMID- 19088290
TI  - A newly recognized hantavirus in the Asian house rat (Rattus tanezumi) in
      Indonesia.
AB  - Hantaviral sequences were recovered from the lung tissue of an Asian house rat
      (Rattus tanezumi) captured in Serang, Indonesia. Phylogenetic analysis of partial
      L, M and S segment sequences showed that they belonged to a novel hantavirus
      provisionally named Serang virus (SERV). Notably, SERV is distinct from the
      hantaviruses associated with rodents of the species Rattus: Seoul virus
      associated with Rattus norvegicus worldwide and Gou virus isolated from Rattus
      rattus in China. Instead SERV appeared more closely related to Thailand virus
      (THAIV) carried by the great bandicoot rat (Bandicota indica). These results
      suggest the possibility that SERV originated via host-switching, with a possible
      scenario of (pre)-THAIV 'jumping' from (pre)bandicoots to rats and colonizing
      this new host species.

PMID- 19088291
TI  - Crimean-Congo hemorrhagic fever virus entry and replication is clathrin-, pH- and
      cholesterol-dependent.
AB  - To date, the entry pathway and replication mechanisms for members of the family
      Bunyaviridae, and especially for Crimean-Congo hemorrhagic fever virus (CCHFV),
      are poorly understood. Considering the severity of disease and the widespread
      geographical occurrence of CCHFV, investigating viral entry is of great value for
      development of antivirals. In this study, we have shown that knockdown of
      clathrin by small interfering RNA significantly reduced CCHFV nucleocapsid
      protein and viral RNA levels, suggesting that CCHFV utilizes clathrin-dependent
      endocytosis. In contrast, caveolin-1, an important constituent of caveolae
      endocytosis, is not important in CCHFV infection. Moreover, treatment with drugs
      that are known to interfere with the formation of clathrin-coated pits (sucrose
      and chlorpromazine) or endosome acidification (bafilomycin A1 and NH(4)Cl) also
      supported a clathrin-dependent pathway in the entry process of CCHFV. Finally, we
      demonstrated that cholesterol depletion in the cell plasma membrane significantly
      inhibited CCHFV infection. In the presence of exogenous cholesterol, this process
      was reversed, suggesting that cholesterol is important in the life cycle of
      CCHFV.

PMID- 19088292
TI  - Indigenous sources of 2007-2008 H5N1 avian influenza outbreaks in Thailand.
AB  - Outbreaks of H5N1 avian influenza show strong seasonality. It is not clear where
      the source of virus originates from in each new outbreak season. This study
      sought to understand the nature of viral resurgence in recent outbreak seasons in
      Thailand, where the epidemic is relatively well controlled. In such a situation,
      indigenous viruses surviving the inter-outbreak season would have to pass through
      a bottleneck. In order to look for evidence of the bottleneck effect, viral
      genome sequences from recent outbreaks in the country were analysed. H5N1 avian
      influenza viruses were isolated from six outbreaks in the rainy season and winter
      of 2007 through to early 2008. Most of the outbreaks were in the Yom-Nan River
      basin in the southern part of the northern region of the country. Sequences of
      these viral isolates were identified as clade 1, genotype Z, similar to viruses
      from previous years in the central region of the country. The sequences clustered
      into two groups, one of which was closely related to viruses isolated from the
      same area in July 2006. These analyses indicated that there was a strong
      bottleneck effect on the virus population and that only a few lineages remained
      in the area. In addition, evidence of reassortment among these viruses was found.
      These indicated re-emergence of viruses from a small pool of indigenous sources
      that had been silently perpetuated over the dry summer months. Therefore, an
      approach to eradicate H5N1 avian influenza from the area by eliminating these
      local reservoirs may be feasible and should be seriously considered.

PMID- 19088293
TI  - Genetic characterization of orthobunyavirus Melao, strains BE AR633512 and BE
      AR8033, and experimental infection in golden hamsters (Mesocricetus auratus).
AB  - Melao virus (MELV) strains BE AR8033 and BE AR633512 were isolated from pools of
      Ochlerotatus scapularis mosquitoes in Belem, Para State (1955), and Alta
      Floresta, Rondonia State (2000), Brazil, respectively. The aim of the present
      study was to molecularly characterize these strains and to describe the
      histopathological, biochemical and immunological changes in golden hamsters
      (Mesocricetus auratus) following intraperitoneal injection of MELV strains.
      Hamsters were susceptible to both of the MELV strains studied. Viraemia was
      observed 3-6 days post-infection (p.i.) for BE AR633512 and only on the second
      day p.i. for BE AR8033. Neutralizing antibodies against both strains were
      detected in blood samples obtained at 5 days p.i. and persisted up to 30 days
      p.i. Aspartate aminotransferase, alanine aminotransferase and blood urea nitrogen
      were significantly altered in animals infected with the two MELV strains, while
      creatinine was only altered in animals inoculated with BE AR633512.
      Histopathological changes were observed in the central nervous system, liver,
      kidney and spleen of hamsters, and infection was confirmed by detection of
      specific MELV antigens by immunohistochemistry. Strain BE AR633512 caused more
      severe tissue damage than strain BE AR8033, showing increased neurovirulence and
      pathogenicity. Genetic analysis based on the full-length sequences of the
      glycoprotein (Gn and Gc) and nucleocapsid protein (N) genes revealed high levels
      of homology between the MELV strains. Interestingly, the greatest genetic
      divergence was found for the Gn gene of strain BE AR633512, in which several
      synonymous and non-synonymous mutations causing changes in RNA secondary
      structure were observed. Further studies will be necessary to investigate the
      role of Gn and Gc mutations in the MELV pathogenicity.

PMID- 19088294
TI  - Cyanovirin-N potently inhibits human immunodeficiency virus type 1 infection in
      cellular and cervical explant models.
AB  - In the absence of a protective vaccine against human immunodeficiency virus
      (HIV), there is an urgent need for the development of effective topical
      microbicides to prevent HIV infection. Candidate vaginal microbicides should
      provide protection against circulating strains, be cheap, stable on storage, safe
      and easy to use. Here we describe a detailed study of the safety and efficacy of
      Cyanovirin-N (CV-N) in vitro, and in an ex vivo model of female genital tissue
      explants. CV-N demonstrated potent activity in the low nanomolar range against
      laboratory and primary isolates. Activity was related to the affinity of CV-N for
      binding to whole virions as determined by acoustic resonance. Potent activity was
      also observed against cell-associated HIV-1, although slightly reduced. CV-N
      activity in the presence of whole semen was reduced by 7-10-fold, although it
      remained in the low nanomolar range and was minimally modified by the presence of
      Candida albicans. Furthermore, CV-N potently inhibited infection of ectocervical
      explants and virus dissemination by tissue-emigrating cells. In peripheral blood
      mononuclear cell (PBMC) assays, CV-N was shown to have some mitogenic activity
      following 3 days exposure to compound, and this was associated with a modest
      increase in expression of gamma interferon, stromal cell-derived factor 1beta and
      interleukin 4. However, 2 h exposure to CV-N had no effect on cytokine expression
      in PBMC or tissue explant culture over a 24 h period, suggesting that the
      potential for inflammation is low. Data presented here indicate that targeting
      HIV envelope glycoproteins may provide an effective strategy to prevent HIV-1
      infection mediated by either cell-free virus or infected cells.

PMID- 19088295
TI  - The acquisition of molecular determinants involved in potato virus Y necrosis
      capacity leads to fitness reduction in tobacco plants.
AB  - The prevalence of necrotic potato virus Y (PVY) in natural populations could
      reflect increased fitness of necrotic isolates. In this paper, the effects of the
      acquisition of molecular determinants (A/G(2213) and A/C(2271)) involved in
      necrosis capacity on both the number of progeny produced and the competitiveness
      of PVY were characterized. The relationship between necrosis and fitness was
      tested using (i) Nicotiana tabacum cv. Xanthi and Nicotiana clevelandii, (ii)
      necrotic PVY(N)-605 and non-necrotic PVY(O)-139 isolates, (iii) single-mutated
      (PVY(KR) and PVY(ED)) and double-mutated (PVY(KRED)) versions of PVY(N)-605 and
      (iv) three quantitative PCR assays specific for nt A(2213), G(2213) and A(2271)
      of the PVY genome. The data demonstrated effects of both the genetic background
      and nt 2213 and 2271 on the fitness of PVY. Quantification of PVY RNA in singly
      infected plants revealed that both the PVY(N)-605 genetic background and the
      acquisition of necrotic capacity resulted in a decrease in the number of progeny
      produced. Competition experiments revealed that the genetic background of PVY(N)
      had a positive impact on competitiveness. In contrast, nucleotides involved in
      necrotic properties were associated with decreased fitness. Finally, in the host
      that did not respond to infection with necrosis, the benefit associated with the
      PVY(N)-605 genetic background was higher than the cost associated with the
      acquisition of molecular determinants involved in necrosis capacity. The opposite
      result was obtained in the host responding to the infection with necrosis. These
      results indicate that the emergence of necrotic isolates from a non-necrotic
      population is unlikely in tobacco.

PMID- 19088296
TI  - Identification of sequence elements regulating promoter activity and replication
      of a monopartite begomovirus-associated DNA beta satellite.
AB  - DNA beta is a circular single-stranded satellite DNA associated with certain
      monopartite begomoviruses (family Geminiviridae) which causes economically
      important diseases such as cotton leaf curl disease. DNA beta contains a single
      gene, betaC1, which encodes a pathogenicity protein responsible for symptom
      production. Transient expression studies in Nicotiana tabacum using the beta
      glucuronidase reporter gene driven by a betaC1 promoter-deletion series of the
      DNA beta associated with cotton leaf curl Multan virus identified a 68 nt region
      (between -139 and -207) which is important for betaC1 transcription. This 68 nt
      region contains a G-box (CACGTG) located 143 nt upstream of the betaC1 start
      codon. Mutation of the G-box resulted in a significant reduction in betaC1
      promoter activity and DNA beta replication efficiency. In addition, the G-box
      motif was found to bind specifically to a protein(s) in nuclear extracts prepared
      from tobacco leaf tissues. Our results indicate that interaction of the G-box
      motif with host nuclear factors is important for efficient gene expression and
      replication of DNA beta.

PMID- 19088297
TI  - Alteration of the biological and biochemical characteristics of bovine spongiform
      encephalopathy prions during interspecies transmission in transgenic mice models.
AB  - In the interspecies transmission of prions, the species barrier influences the
      susceptibility of the host. Bovine spongiform encephalopathy (BSE) prions affect
      a wide range of host species but do not affect hamsters. In order to study this
      species barrier, this study analysed the transmissibility of BSE prions to
      several lines of transgenic (Tg) mice, including those expressing mouse and
      hamster chimeric prion proteins (MH2M and MHM2 mice). BSE prions were transmitted
      to tga20, MHM2 and ICR mice, and the incubation period was approximately 400
      days. Thus, these mice were classified as 'susceptible mice'. However, BSE prions
      were not transmitted to MH2M and TgHaNSE mice, and these mice were classified as
      'resistant mice'. After the BSE prions were passaged once in wild-type mice, they
      could be transmitted to resistant mice. The characteristics of the accumulated
      abnormal isoform of PrP (PrP(Sc)) in susceptible and resistant mice were
      determined using Western blotting. A BSE-like glycoform pattern of PrP(Sc) was
      detected in all of the susceptible mice using two different antibodies that
      recognized either the N- or the C-terminal end of the 27-30 kDa protease
      resistant fragment of PrP (PrP(27-30)) as the epitope. In contrast, proteinase
      digestion followed by deglycosylation analysis showed that, in addition to PrP(27
      30), truncated PrP(Sc) fragments existed in resistant mice. These mixed PrP(Sc)
      fragments may have resulted from the adaptation of resistant mice to BSE prions.

PMID- 19088298
TI  - Microinjection of lentiviral vectors expressing small interfering RNAs directed
      against laminin receptor precursor mRNA prolongs the pre-clinical phase in
      scrapie-infected mice.
AB  - We examined therapeutic in vitro and in vivo approaches using lentivirus-based
      packaging of small interfering RNAs (siRNAs) targeting the non-integrin laminin
      receptor mRNA for treatment and prevention of prion disorders. Transfection of
      N2aSc(+) cells with recombinant plasmids expressing three different siRNAs,
      significantly reduced both the LRP (laminin receptor precursor) and PrP(Sc)
      levels by approximately 40-60 %. Stereotactic intracerebral microinjection of
      recombinant lentiviral vectors LVsiRNA-LRP 7 and 9 into the cortex of C57BL/6
      wild-type mice resulted in a significant reduction of the LR levels in the cortex
      15 days post-injection by 62 and 82 %, respectively. Intracerebral RML
      inoculation of C57BL/6 mice after microinjection with recombinant lentiviral
      vector LVsiRNA-LRP 7 into the hippocampus resulted in a significant reduction of
      both LRP and PrP(Sc) levels by 36 and 41 %, respectively, concomitant with a
      significant prolongation of the pre-clinical phase. Lentiviral vectors expressing
      siRNAs targeting LRP mRNA represent a novel delivery system for the treatment of
      transmissible spongiform encephalopathies.

PMID- 19088299
TI  - Pathogenic prion protein is degraded by a manganese oxide mineral found in soils.
AB  - Prions, the aetiological agents of transmissible spongiform encephalopathies,
      exhibit extreme resistance to degradation. Soil can retain prion infectivity in
      the environment for years. Reactive soil components may, however, contribute to
      the inactivation of prions in soil. Members of the birnessite family of manganese
      oxides (MnO(2)) rank among the strongest natural oxidants in soils. Here, we
      report the abiotic degradation of pathogenic prion protein (PrP(TSE)) by a
      synthetic analogue of naturally occurring birnessite minerals. Aqueous MnO(2)
      suspensions degraded the PrP(TSE) as evidenced by decreased immunoreactivity and
      diminished ability to seed protein misfolding cyclic amplification reactions.
      Birnessite-mediated PrP(TSE) degradation increased as a solution's pH decreased,
      consistent with the pH-dependence of the redox potential of MnO(2). Exposure to
      5.6 mg MnO(2) ml(-1) (PrP(TSE) : MnO(2)=1 : 110) decreased PrP(TSE) levels by >
      or = 4 orders of magnitude. Manganese oxides may contribute to prion degradation
      in soil environments rich in these minerals.

PMID- 19088300
TI  - The behavioral and neurochemical effects of a novel D-amino acid oxidase
      inhibitor compound 8 [4H-thieno [3,2-b]pyrrole-5-carboxylic acid] and D-serine.
AB  - Multiple studies indicate that N-methyl-D-aspartate (NMDA) receptor hypofunction
      underlies some of the deficits associated with schizophrenia. One approach for
      improving NMDA receptor function is to enhance occupancy of the glycine
      modulatory site on the NMDA receptor by increasing the availability of the
      endogenous coagonists D-serine. Here, we characterized a novel D-amino acid
      oxidase (DAAO) inhibitor, compound 8 [4H-thieno [3,2-b]pyrrole-5-carboxylic acid]
      and compared it with D-serine. Compound 8 is a moderately potent inhibitor of
      human (IC(50), 145 nM) and rat (IC(50), 114 nM) DAAO in vitro. In rats, compound
      8 (200 mg/kg) decreased kidney DAAO activity by approximately 96% and brain DAAO
      activity by approximately 80%. This marked decrease in DAAO activity resulted in
      a significant (p < 0.001) elevation in both plasma (220% of control) and
      cerebrospinal fluid (CSF; 175% of control) D-serine concentration. However,
      compound 8 failed to significantly influence amphetamine-induced psychomotor
      activity, nucleus accumbens dopamine release, or an MK-801 (dizocilpine maleate)
      induced deficit in novel object recognition in rats. In contrast, high doses of D
      serine attenuated both amphetamine-induced psychomotor activity and dopamine
      release and also improved performance in novel object recognition. Behaviorally
      efficacious doses of D-serine (1280 mg/kg) increased CSF levels of D-serine 40
      fold above that achieved by the maximal dose of compound 8. These findings
      demonstrate that pharmacological inhibition of DAAO significantly increases D
      serine concentration in the periphery and central nervous system. However, acute
      inhibition of DAAO appears not to be sufficient to increase D-serine to
      concentrations required to produce antipsychotic and cognitive enhancing effects
      similar to those observed after administration of high doses of exogenous D
      serine.

PMID- 19088301
TI  - Nicotinic receptor activation increases [3H]dopamine uptake and cell surface
      expression of dopamine transporters in rat prefrontal cortex.
AB  - Previous research shows that nicotine increases dopamine (DA) clearance in rat
      prefrontal cortex (PFC) and striatum via a nicotinic receptor (nAChR)-mediated
      mechanism. The present study investigated whether activation of nAChRs regulates
      DA transporter (DAT) function through a trafficking-dependent mechanism. After
      nicotine administration (0, 0.3, and 0.8 mg/kg s.c., 15-1440 min after
      injection), DAT function and trafficking in synaptosomes of PFC and striatum were
      determined. nAChR mediation of the effect of nicotine on DAT function and
      trafficking in PFC was determined by pretreatment with mecamylamine, dihydro-beta
      erythroidine, or methyllycaconitine. Nicotine (0.8 mg/kg, 15 and 30 min after
      injection) increased the maximal velocity (V(max)) of [3H]DA uptake in PFC with
      no change in K(m), compared with control. Biotinylation and Western blot assays
      showed that nicotine (0.8 mg/kg; 30 min) increased DAT cell surface expression in
      PFC. In contrast, a lower dose of nicotine (0.3 mg/kg; 30 min) did not alter DAT
      function and trafficking in PFC. Pretreatment with mecamylamine, dihydro-beta
      erythroidine, or methyllycaconitine (1.5, 8.0, and 10.0 mg/kg s.c., respectively)
      completely blocked the nicotine-induced increase in V(max) in PFC. In addition,
      mecamylamine completely blocked the nicotine-induced increase in DAT cell surface
      expression in PFC. Nicotine did not increase DAT function and cell surface
      expression in striatum, indicating that nicotine modulates DAT function in a
      brain region-specific manner. Thus, results from the present study suggest that
      the nicotine-induced increases in DAT function and cell surface expression in PFC
      may mediate some of the behavioral effects of nicotine.

PMID- 19088302
TI  - The effect of a chimeric human/murine anti-cocaine monoclonal antibody on cocaine
      self-administration in rats.
AB  - The predominantly human sequence anti-cocaine monoclonal antibody (mAb), 2E2, has
      high affinity and specificity for cocaine and antagonizes cocaine distribution to
      the brain in mice. To determine whether 2E2 can alter the self-administration of
      cocaine in rats, both cocaine-induced reinstatement (priming) of self
      administration, and the rates of cocaine consumption were assessed during daily
      sessions. After self-administration training, the rats' cocaine priming threshold
      values were stable over a 2-week baseline period. Furthermore, the rates of
      cocaine consumption at unit doses of 0.3 and 3.0 micromol/kg were steady within
      sessions and stable between sessions. Then, 2E2 (120 mg/kg i.v.) or an equivalent
      dose of nonspecific human polyclonal IgG (control) was infused and daily sessions
      continued. 2E2 produced an initial, approximately 3-fold, increase in the cocaine
      priming threshold that declined toward baseline values over the subsequent 3
      weeks, with an effect t((1/2)) of approximately 4 days. In contrast to the
      substantial increase in the cocaine priming threshold, 2E2 produced only modest
      dose-dependent increases (42 and 18%) in the cocaine consumption rates, and these
      also gradually declined toward baseline values. There was no significant effect
      of the control IgG on the priming threshold or rates of consumption of cocaine.
      After infusion, antibody blood concentrations declined over time, and a two
      compartment pharmacokinetic model generated values for the distribution and
      elimination half-lives of 0.5 and 11.6 days for 2E2 and 0.4 and 6.0 days for
      control IgG. 2E2 had a long-lasting effect on cocaine-induced priming, which may
      predict its efficacy as an immunotherapy for cocaine abuse.

PMID- 19088303
TI  - Kinetics of cellular retention during Caco-2 permeation experiments: role of
      lysosomal sequestration and impact on permeability estimates.
AB  - The permeability estimation from cell monolayer permeation data is usually based
      on 100% recovery assumption. However, poor recovery is often seen in such
      experiments in practice but often neglected in data interpretation. In the
      present study, the cellular retention kinetics during Caco-2 permeation
      experiments of three passively transported compounds, weakly basic propranolol
      [(+/-)-1-isopropylamino-3-(1-naphthyloxy)-2-propanol], weakly acidic ibuprofen
      [alpha-methyl-4-(isobutyl)phenylacetic acid], and neutral testosterone (17beta
      hydroxy-4-androsten-3-one), were determined. Furthermore, the effects of cellular
      retention kinetics on apparent permeability were evaluated, and the role of
      lysosomal sequestration in cellular retention of propranolol was explored. The
      cellular retention profiles were observed to be direction and concentration
      dependent, which may cause erroneous directionality and concentration dependence
      in permeability estimates. Furthermore, the lysosomal sequestration was
      demonstrated to contribute to the extent and kinetics of the cellular retention
      of propranolol.

PMID- 19088304
TI  - MicroRNA target prediction by expression analysis of host genes.
AB  - MicroRNAs (miRNAs) are small noncoding RNAs that control gene expression by
      inducing RNA cleavage or translational inhibition. Most human miRNAs are
      intragenic and are transcribed as part of their hosting transcription units. We
      hypothesized that the expression profiles of miRNA host genes and of their
      targets are inversely correlated and devised a novel procedure, HOCTAR (host gene
      oppositely correlated targets), which ranks predicted miRNA target genes based on
      their anti-correlated expression behavior relative to their respective miRNA host
      genes. HOCTAR is the first tool for systematic miRNA target prediction that
      utilizes the same set of microarray experiments to monitor the expression of both
      miRNAs (through their host genes) and candidate targets. We applied the procedure
      to 178 human intragenic miRNAs and found that it performs better than currently
      available prediction softwares in pinpointing previously validated miRNA targets.
      The high-scoring HOCTAR predicted targets were enriched in Gene Ontology
      categories, which were consistent with previously published data, as in the case
      of miR-106b and miR-93. By means of overexpression and loss-of-function assays,
      we also demonstrated that HOCTAR is efficient in predicting novel miRNA targets
      and we identified, by microarray and qRT-PCR procedures, 34 and 28 novel targets
      for miR-26b and miR-98, respectively. Overall, we believe that the use of HOCTAR
      significantly reduces the number of candidate miRNA targets to be tested compared
      to the procedures based solely on target sequence recognition. Finally, our data
      further confirm that miRNAs have a significant impact on the mRNA levels of most
      of their targets.

PMID- 19088305
TI  - A high-density SNP-based linkage map of the chicken genome reveals sequence
      features correlated with recombination rate.
AB  - The resolution of the chicken consensus linkage map has been dramatically
      improved in this study by genotyping 12,945 single nucleotide polymorphisms
      (SNPs) on three existing mapping populations in chicken: the Wageningen (WU),
      East Lansing (EL), and Uppsala (UPP) mapping populations. As many as 8599 SNPs
      could be included, bringing the total number of markers in the current consensus
      linkage map to 9268. The total length of the sex average map is 3228 cM,
      considerably smaller than previous estimates using the WU and EL populations,
      reflecting the higher quality of the new map. The current map consists of 34
      linkage groups and covers at least 29 of the 38 autosomes. Sex-specific analysis
      and comparisons of the maps based on the three individual populations showed
      prominent heterogeneity in recombination rates between populations, but no
      significant heterogeneity between sexes. The recombination rates in the F(1) Red
      Jungle fowl/White Leghorn males and females were significantly lower compared
      with those in the WU broiler population, consistent with a higher recombination
      rate in purebred domestic animals under strong artificial selection. The
      recombination rate varied considerably among chromosomes as well as along
      individual chromosomes. An analysis of the sequence composition at recombination
      hot and cold spots revealed a strong positive correlation between GC-rich
      sequences and high recombination rates. The GC-rich cohesin binding sites in
      particular stood out from other GC-rich sequences with a 3.4-fold higher density
      at recombination hot spots versus cold spots, suggesting a functional
      relationship between recombination frequency and cohesin binding.

PMID- 19088306
TI  - Genome-wide profiling of salt fractions maps physical properties of chromatin.
AB  - We applied genome-wide profiling to successive salt-extracted fractions of
      micrococcal nuclease-treated Drosophila chromatin. Chromatin fractions extracted
      with 80 mM or 150 mM NaCl after digestion contain predominantly mononucleosomes
      and represent classical "active" chromatin. Profiles of these low-salt soluble
      fractions display phased nucleosomes over transcriptionally active genes that are
      locally depleted of histone H3.3 and correspond closely to profiles of histone
      H2Av (H2A.Z) and RNA polymerase II. This correspondence suggests that
      transcription can result in loss of H3.3+H2Av nucleosomes and generate low-salt
      soluble nucleosomes. Nearly quantitative recovery of chromatin is obtained with
      600 mM NaCl; however, the remaining insoluble chromatin is enriched in actively
      transcribed regions. Salt-insoluble chromatin likely represents oligonucleosomes
      that are attached to large protein complexes. Both low-salt extracted and
      insoluble chromatin are rich in sequences that correspond to epigenetic
      regulatory elements genome-wide. The presence of active chromatin at both
      extremes of salt solubility suggests that these salt fractions capture bound and
      unbound intermediates in active processes, thus providing a simple, powerful
      strategy for mapping epigenome dynamics.

PMID- 19088307
TI  - Molecular ecological analysis of fecal bacterial populations from term infants
      fed formula supplemented with selected blends of prebiotics.
AB  - Supplementation of infant formulas with prebiotic ingredients continues the
      effort to mimic functional properties of human milk. In this double-blind,
      controlled, 28-day study, healthy term infants received control formula (control
      group; n = 25) or control formula supplemented with polydextrose (PDX) and
      galactooligosaccharide (GOS) (4 g/liter) (PG4 group; n = 27) or with PDX, GOS,
      and lactulose (LOS) (either 4 g/liter [PGL4 group; n = 27] or 8 g/liter [PGL8
      group; n = 25]). A parallel breast-fed group (BF group) (n = 30) was included.
      Stool characteristics, formula tolerance, and adverse events were monitored.
      Fecal bacterial subpopulations were evaluated by culture-based selective
      enumeration (Enterobacteriaceae), quantitative real-time PCR (Clostridium
      clusters I, XI, and XIV, Lactobacillus, and Bifidobacterium), and fluorescence in
      situ hybridization (FISH) (Bifidobacterium). Fecal bacterial community profiles
      were examined by using 16S rRNA gene PCR-denaturing gradient gel electrophoresis.
      The daily stool consistency was significantly softer or looser in the BF group
      than in all of the groups that received formula. The formulas were well
      tolerated, and the incidences of adverse events did not differ among feeding
      groups. Few significant changes in bacterial subpopulations were observed at any
      time point. The bacterial communities were stable; individual profiles tended to
      cluster by subject rather than by group. Post hoc analysis, however, demonstrated
      that the bacterial community profiles for subjects in the BF, PG4, PGL4, and PGL8
      groups that first received formula at a younger age were less stable than the
      profiles for subjects in the same groups that received formula at an older age,
      but there was no difference for the control group. These data indicate that
      formulas containing PDX, GOS, and LOS blends are more likely to influence gut
      microbes when administration is begun in early infancy and justify further
      investigation of the age-related effects of these blends on fecal microbiota.

PMID- 19088308
TI  - Isolation of bifidobacteria from breast milk and assessment of the
      bifidobacterial population by PCR-denaturing gradient gel electrophoresis and
      quantitative real-time PCR.
AB  - The objective of this work was to elucidate if breast milk contains
      bifidobacteria and whether they can be transmitted to the infant gut through
      breastfeeding. Twenty-three women and their respective infants provided samples
      of breast milk and feces, respectively, at days 4 to 7 after birth. Gram-positive
      and catalase-negative isolates from specific media with typical bifidobacterial
      shapes were identified to the genus level by F6PPK (fructose-6-phosphate
      phosphoketolase) assays and to the species level by 16S rRNA gene sequencing.
      Bifidobacterial communities in breast milk were assessed by PCR-denaturing
      gradient gel electrophoresis (PCR-DGGE), and their levels were estimated by
      quantitative real-time PCR (qRTi-PCR). Bifidobacteria were present in 8 milk
      samples and 21 fecal samples. Bifidobacterium breve, B. adolescentis, and B.
      bifidum were isolated from milk samples, while infant feces also contained B.
      longum and B. pseudocatenulatum. PCR-DGGE revealed the presence of one to four
      dominant bifidobacterial bands in 22 milk samples. Sequences with similarities
      above 98% were identified as Bifidobacterium breve, B. adolescentis, B. longum,
      B. bifidum, and B. dentium. Bifidobacterial DNA was detected by qRTi-PCR in the
      same 22 milk samples at a range between 40 and 10,000 16S rRNA gene copies per
      ml. In conclusion, human milk seems to be a source of living bifidobacteria for
      the infant gut.

PMID- 19088309
TI  - From local surveys to global surveillance: three high-throughput genotyping
      methods for epidemiological monitoring of Xanthomonas citri pv. citri pathotypes.
AB  - Asiatic citrus canker is a major disease worldwide, and its causal agent,
      Xanthomonas citri pv. citri, is listed as a quarantine organism in many
      countries. Analysis of the molecular epidemiology of this bacterium is hindered
      by a lack of molecular typing techniques suitable for surveillance and outbreak
      investigation. We report a comparative evaluation of three typing techniques,
      amplified fragment length polymorphism (AFLP) analysis, insertion sequence
      ligation-mediated PCR (IS-LM-PCR) typing, and multilocus variable-number tandem
      repeat analysis (MLVA), with 234 strains originating from Asia, the likely center
      of origin of the pathogen, and reference strains of pathotypes A, A*, and A(w),
      which differ in host range. The typing techniques were congruent in describing
      the diversity of this strain collection, suggesting that the evolution pattern of
      the bacterium may be clonal. Based on a hierarchical analysis of molecular
      variance, the AFLP method best described the genetic variation found among
      pathotypes whereas MLVA best described the variation found among individual
      strains from the same countries or groups of neighboring countries. IS-LM-PCR
      data suggested that the transposition of insertion sequences in the genome of X.
      citri pv. citri occurs rarely enough not to disturb the phylogenetic signal. This
      technique may be useful for the global surveillance of non-epidemiologically
      related strains. Although pathological characteristics of strains could be most
      often predicted from genotyping data, we report the occurrence in the Indian
      peninsula of strains genetically related to pathotype A* strains but with a host
      range similar to that of pathotype A, which makes the classification of this
      bacterium even more complicated.

PMID- 19088310
TI  - Bile affects the synthesis of exopolysaccharides by Bifidobacterium animalis.
AB  - By using cryo-scanning electron microscopy and quantification with lectin
      conjugated probes, we have detected the production of exopolysaccharides (EPS) in
      Bifidobacterium animalis subsp. lactis in the presence of bile. In addition, the
      expression of gtf01207, which codifies a putative priming glycosyltransferase
      involved in EPS synthesis, was induced by bile.

PMID- 19088311
TI  - Application of denaturing high-performance liquid chromatography in microbial
      ecology: fermentor sludge, compost, and soil community profiling.
AB  - Genetic fingerprinting methods, such as denaturing gradient gel electrophoresis
      (DGGE), are used in microbial ecology for the analysis of mixed microbial
      communities but are associated with various problems. In the present study we
      used a new alternative method: denaturing high-performance liquid chromatography
      (dHPLC). This method was previously shown to work with samples from water and gut
      flora but had not yet been applied to complex environmental samples. In contrast
      to other publications dealing with dHPLC, we used a commonly available HPLC
      system. Samples from different origins (fermentor sludge, compost, and soil), all
      ecologically significant, were tested, and the 16S rRNA gene was amplified via
      PCR. After optimization of the HPLC elution conditions, amplicons of pure
      cultures and mixed microbial populations could be separated successfully.
      Systematic differentiation was carried out by a cloning approach, since fraction
      collection of the peaks did not result in satisfactory fragment separation. dHPLC
      was evaluated as a tool for microbial community analysis on a genetic level and
      demonstrated major improvements compared to gel-based fingerprinting methods,
      such as DGGE, that are commonly used in microbial ecology.

PMID- 19088312
TI  - Linking sequence to function in soil bacteria: sequence-directed isolation of
      novel bacteria contributing to soilborne plant disease suppression.
AB  - Microbial community profiling of samples differing in a specific ecological
      function, i.e., soilborne plant disease suppression, can be used to mark,
      recover, and ultimately identify the bacteria responsible for that specific
      function. Previously, several terminal restriction fragments (TRF) of 16S rRNA
      genes were statistically associated with damping-off disease suppression. This
      work presents the development of sequence-based TRF length polymorphism (T-RFLP)
      derived molecular markers to direct the identification and isolation of novel
      bacteria involved in damping-off pathogen suppression. Multiple sequences
      matching TRF M139 and M141 were cloned and displayed identity to multiple
      database entries in the genera incertae sedis of the Burkholderiales. Sequences
      matching TRF M148, in contrast, displayed greater sequence diversity. A sequence
      directed culturing strategy was developed using M139- and M141-derived markers
      and media reported to be selective for the genera identified within this group.
      Using this approach, we isolated and identified novel Mitsuaria and Burkholderia
      species with high levels of sequence similarity to the targeted M139 and M141
      TRF, respectively. As predicted, these Mitsuaria and Burkholderia isolates
      displayed the targeted function by reducing fungal and oomycete plant pathogen
      growth in vitro and reducing disease severity in infected tomato and soybean
      seedlings. This work represents the first successful example of the use of T-RFLP
      derived markers to direct the isolation of microbes with pathogen-suppressing
      activities, and it establishes the power of low-cost molecular screening to
      identify and direct the recovery of functionally important microbes, such as
      these novel biocontrol strains.

PMID- 19088313
TI  - Identification of freshwater Phycodnaviridae and their potential phytoplankton
      hosts, using DNA pol sequence fragments and a genetic-distance analysis.
AB  - Viruses that infect phytoplankton are an important component of aquatic
      ecosystems, yet in lakes they remain largely unstudied. In order to investigate
      viruses (Phycodnaviridae) infecting eukaryotic phytoplankton in lakes and to
      estimate the number of potential host species, samples were collected from four
      lakes at the Experimental Lakes Area in Ontario, Canada, during the ice-free
      period (mid-May to mid-October) of 2004. From each lake, Phycodnaviridae DNA
      polymerase (pol) gene fragments were amplified using algal-virus-specific primers
      and separated by denaturing gradient gel electrophoresis; 20 bands were extracted
      from the gels and sequenced. Phylogenetic analysis indicated that freshwater
      environmental phycodnavirus sequences belong to distinct phylogenetic groups. An
      analysis of the genetic distances "within" and "between" monophyletic groups of
      phycodnavirus isolates indicated that DNA pol sequences that differed by more
      than 7% at the inferred amino acid level were from viruses that infect different
      host species. Application of this threshold to phylogenies of environmental
      sequences indicated that the DNA pol sequences from these lakes came from viruses
      that infect at least nine different phytoplankton species. A multivariate
      statistical analysis suggested that potential freshwater hosts included
      Mallomonas sp., Monoraphidium sp., and Cyclotella sp. This approach should help
      to unravel the relationships between viruses in the environment and the
      phytoplankton hosts they infect.

PMID- 19088314
TI  - A chromosomally located traHIJKCLMN operon encoding a putative type IV secretion
      system is involved in the virulence of Yersinia ruckeri.
AB  - Nucleotide sequence analysis of the region surrounding the pIVET8 insertion site
      in Yersinia ruckeri 150RiviXII, previously selected by in vivo expression
      technology (IVET), revealed the presence of eight genes (traHIJKCLMN [hereafter
      referred to collectively as the tra operon or tra cluster]), which are similar
      both in sequence and organization to the tra operon cluster found in the
      virulence-related plasmid pADAP from Serratia entomophila. Interestingly, the tra
      cluster of Y. ruckeri is chromosomally encoded, and no similar tra cluster has
      been identified yet in the genomic analysis of human pathogenic yersiniae. A traI
      insertional mutant was obtained by homologous recombination. Coinfection
      experiments with the mutant and the parental strain, as well as 50% lethal dose
      determinations, indicate that this operon is involved in the virulence of this
      bacterium. All of these results suggest the implication of the tra cluster in a
      virulence-related type IV secretion/transfer system. Reverse transcriptase PCR
      studies showed that this cluster is transcribed as an operon from a putative
      promoter located upstream of traH and that the mutation of traI had a polar
      effect. A traI::lacZY transcriptional fusion displayed higher expression levels
      at 18 degrees C, the temperature of occurrence of the disease, and under nutrient
      limiting conditions. PCR detection analysis indicated that the tra cluster is
      present in 15 Y. ruckeri strains from different origins and with different
      plasmid profiles. The results obtained in the present study support the
      conclusion, already suggested by different authors, that Y. ruckeri is a very
      homogeneous species that is quite different from the other members of the genus
      Yersinia.

PMID- 19088316
TI  - Role of germinant receptors in Caco-2 cell-initiated germination of Bacillus
      cereus ATCC 14579 endospores.
AB  - Spores obtained from Bacillus cereus ATCC 14579 and mutant strains lacking each
      of seven germinant receptor operons were exposed to differentiated Caco-2 cells
      and monitored for germination. Spores of the gerI and gerL mutants showed a
      reduced germination response, pointing to a role for these receptors in Caco-2
      induced germination.

PMID- 19088315
TI  - Atypical biosynthetic properties of a Delta 12/nu+3 desaturase from the model
      basidiomycete Phanerochaete chrysosporium.
AB  - The model white-rot basidiomycete Phanerochaete chrysosporium contains a single
      integral membrane Delta(12)-desaturase FAD2 related to the endoplasmic reticular
      plant FAD2 enzymes. The fungal fad2-like gene was cloned and distinguished itself
      from plant homologs by the presence of four introns and a significantly larger
      coding region. The coding sequence exhibits ca. 35% sequence identity to plant
      homologs, with the highest sequence conservation found in the putative catalytic
      and major structural domains. In vivo activity of the heterologously expressed
      enzyme favors C(18) substrates with nu+3 regioselectivity, where the site of
      desaturation is three carbons carboxy-distal to the reference position of a
      preexisting double bond (nu). Linoleate accumulated to levels in excess of 12% of
      the total fatty acids upon heterologous expression of P. chrysosporium FAD2 in
      Saccharomyces cerevisiae. In contrast to the behavior of the plant FAD2 enzymes,
      this oleate desaturase does not 12-hydroxylate lipids and is the first example
      whose activity increases at higher temperatures (30 degrees C versus 15 degrees
      C). Thus, while maintaining the hallmark activity of the fatty acyl Delta(12)
      desaturase family, the basidiomycete fad2 genes appear to have evolved
      substantially from an ancestral desaturase.

PMID- 19088318
TI  - L-valine production during growth of pyruvate dehydrogenase complex-deficient
      Corynebacterium glutamicum in the presence of ethanol or by inactivation of the
      transcriptional regulator SugR.
AB  - Pyruvate dehydrogenase complex-deficient strains of Corynebacterium glutamicum
      produce L-valine from glucose only after depletion of the acetate required for
      growth. Here we show that inactivation of the DeoR-type transcriptional regulator
      SugR or replacement of acetate by ethanol already in course of the growth phase
      results in efficient L-valine production.

PMID- 19088317
TI  - An orphan LuxR homolog of Sinorhizobium meliloti affects stress adaptation and
      competition for nodulation.
AB  - The Sin/ExpR quorum-sensing system of Sinorhizobium meliloti plays an important
      role in the symbiotic association with its host plant, Medicago sativa. The LuxR
      type response regulators of the Sin system include the synthase (SinI)-associated
      SinR and the orphan regulator ExpR. Interestingly, the S. meliloti Rm1021 genome
      codes for four additional putative orphan LuxR homologs whose regulatory roles
      remain to be identified. These response regulators contain the characteristic
      domains of the LuxR family of proteins, which include an N-terminal
      autoinducer/response regulatory domain and a C-terminal helix-turn-helix domain.
      This study elucidates the regulatory role of one of the orphan LuxR-type response
      regulators, NesR. Through expression and phenotypic analyses, nesR was determined
      to affect the active methyl cycle of S. meliloti. Moreover, nesR was shown to
      influence nutritional and stress response activities in S. meliloti. Finally, the
      nesR mutant was deficient in competing with the wild-type strain for plant
      nodulation. Taken together, these results suggest that NesR potentially
      contributes to the adaptability of S. meliloti when it encounters challenges such
      as high osmolarity, nutrient starvation, and/or competition for nodulation, thus
      increasing its chances for survival in the stressful rhizosphere.

PMID- 19088319
TI  - Molecular and biochemical characterization of a beta-fructofuranosidase from
      Xanthophyllomyces dendrorhous.
AB  - An extracellular beta-fructofuranosidase from the yeast Xanthophyllomyces
      dendrorhous was characterized biochemically, molecularly, and phylogenetically.
      This enzyme is a glycoprotein with an estimated molecular mass of 160 kDa, of
      which the N-linked carbohydrate accounts for 60% of the total mass. It displays
      optimum activity at pH 5.0 to 6.5, and its thermophilicity (with maximum activity
      at 65 to 70 degrees C) and thermostability (with a T(50) in the range 66 to 71
      degrees C) is higher than that exhibited by most yeast invertases. The enzyme was
      able to hydrolyze fructosyl-beta-(2-->1)-linked carbohydrates such as sucrose, 1
      kestose, or nystose, although its catalytic efficiency, defined by the
      k(cat)/K(m) ratio, indicates that it hydrolyzes sucrose approximately 4.2 times
      more efficiently than 1-kestose. Unlike other microbial beta-fructofuranosidases,
      the enzyme from X. dendrorhous produces neokestose as the main transglycosylation
      product, a potentially novel bifidogenic trisaccharide. Using a 41% (wt/vol)
      sucrose solution, the maximum fructooligosaccharide concentration reached was
      65.9 g liter(-1). In addition, we isolated and sequenced the X. dendrorhous beta
      fructofuranosidase gene (Xd-INV), showing that it encodes a putative mature
      polypeptide of 595 amino acids and that it shares significant identity with other
      fungal, yeast, and plant beta-fructofuranosidases, all members of family 32 of
      the glycosyl-hydrolases. We demonstrate that the Xd-INV could functionally
      complement the suc2 mutation of Saccharomyces cerevisiae and, finally, a
      structural model of the new enzyme based on the homologous invertase from
      Arabidopsis thaliana has also been obtained.

PMID- 19088320
TI  - Taxonomic structure and monitoring of the dominant population of lactic acid
      bacteria during wheat flour sourdough type I propagation using Lactobacillus
      sanfranciscensis starters.
AB  - The structure and stability of the dominant lactic acid bacterium population were
      assessed during wheat flour sourdough type I propagation by using singly nine
      strains of Lactobacillus sanfranciscensis. Under back-slopping propagation with
      wheat flour type 0 F114, cell numbers of presumptive lactic acid bacteria varied
      slightly between and within starters. As determined by randomly amplified
      polymorphic DNA-PCR and restriction endonuclease analysis-pulsed-field gel
      electrophoresis analyses, only three (LS8, LS14, and LS44) starters dominated
      throughout 10 days of propagation. The others progressively decreased to less
      than 3 log CFU g(-1). Partial sequence analysis of the 16S rRNA and recA genes
      and PCR-denaturating gradient gel electrophoresis analysis using the rpoB gene
      allowed identification of Weissella confusa, Lactobacillus sanfranciscensis,
      Lactobacillus plantarum, Lactobacillus rossiae, Lactobacillus brevis, Lactococcus
      lactis subsp. lactis, Pediococcus pentosaceus, and Lactobacillus spp. as the
      dominant species of the raw wheat flour. At the end of propagation, one
      autochthonous strain of L. sanfranciscensis was found in all the sourdoughs.
      Except for L. brevis, strains of the above species were variously found in the
      mature sourdoughs. Persistent starters were found in association with other
      biotypes of L. sanfranciscensis and with W. confusa or L. plantarum. Sourdoughs
      were characterized for acidification, quotient of fermentation, free amino acids,
      and community-level catabolic profiles by USING Biolog 96-well Eco microplates.
      In particular, catabolic profiles of sourdoughs containing persistent starters
      behaved similarly and were clearly differentiated from the others. The three
      persistent starters were further used for the production of sourdoughs and
      propagated by using another wheat flour whose lactic acid bacterium population in
      part differed from the previous one. Also, in this case all three starter strains
      persisted during propagation.

PMID- 19088321
TI  - Community-level analysis of psbA gene sequences and irgarol tolerance in marine
      periphyton.
AB  - This study analyzes psbA gene sequences, predicted D1 protein sequences, species
      relative abundance, and pollution-induced community tolerance in marine
      periphyton communities exposed to the antifouling compound Irgarol 1051. The
      mechanism of action of Irgarol is the inhibition of photosynthetic electron
      transport at photosystem II by binding to the D1 protein. The metagenome of the
      communities was used to produce clone libraries containing fragments of the psbA
      gene encoding the D1 protein. Community tolerance was quantified with a short
      term test for the inhibition of photosynthesis. The communities were established
      in a continuous flow of natural seawater through microcosms with or without added
      Irgarol. The selection pressure from Irgarol resulted in an altered species
      composition and an inducted community tolerance to Irgarol. Moreover, there was a
      very high diversity in the psbA gene sequences in the periphyton, and the
      composition of psbA and D1 fragments within the communities was dramatically
      altered by increased Irgarol exposure. Even though tolerance to this type of
      compound in land plants often depends on a single amino acid substitution
      (Ser(264)-->Gly) in the D1 protein, this was not the case for marine periphyton
      species. Instead, the tolerance mechanism likely involves increased degradation
      of D1. When we compared sequences from low and high Irgarol exposure, differences
      in nonconserved amino acids were found only in the so-called PEST region of D1,
      which is involved in regulating its degradation. Our results suggest that
      environmental contamination with Irgarol has led to selection for high-turnover
      D1 proteins in marine periphyton communities at the west coast of Sweden.

PMID- 19088322
TI  - MucR, a novel membrane-associated regulator of alginate biosynthesis in
      Pseudomonas aeruginosa.
AB  - Alginate biosynthesis by Pseudomonas aeruginosa was shown to be regulated by the
      intracellular second messenger bis-(3'-5')-cyclic-dimeric-GMP (c-di-GMP), and
      binding of c-di-GMP to the membrane protein Alg44 was required for alginate
      production. In this study, PA1727, a c-di-GMP-synthesizing enzyme was
      functionally analyzed and identified to be involved in regulation of alginate
      production. Deletion of the PA1727 gene in the mucoid alginate-overproducing P.
      aeruginosa strain PDO300 resulted in a nonmucoid phenotype and an about 38-fold
      decrease in alginate production; thus, this gene is designated mucR. The mucoid
      alginate-overproducing phenotype was restored by introducing the mucR gene into
      the isogenic DeltamucR mutant. Moreover, transfer of the MucR-encoding plasmid
      into strain PDO300 led to an about sevenfold increase in alginate production,
      wrinkly colony morphology, increased pellicle formation, auto-aggregation, and
      the formation of highly structured biofilms as well as the inhibition of swarming
      motility. Outer membrane protein profile analysis showed that overproduction of
      MucR mediates a strong reduction in the copy number of FliC (flagellin), required
      for flagellum-mediated motility. Translational reporter enzyme fusions with LacZ
      and PhoA suggested that MucR is located in the cytoplasmic membrane with a
      cytosolic C terminus. Deletion of the proposed C-terminal GGDEF domain abolished
      MucR function. MucR was purified and identified using tryptic peptide
      fingerprinting and matrix-assisted laser desorption ionization-time of flight
      mass spectrometry. Overall, experimental evidence was provided suggesting that
      MucR specifically regulates alginate biosynthesis by activation of alginate
      production through generation of a localized c-di-GMP pool in the vicinity of
      Alg44.

PMID- 19088324
TI  - Clinical development of ixabepilone and other epothilones in patients with
      advanced solid tumors.
AB  - Chemotherapy efficacy in patients with solid tumors is influenced by primary and
      acquired multidrug resistance (MDR). Epothilones represent a novel class of
      microtubule inhibitors with lower susceptibility to drug resistance and efficacy
      in taxane-resistant tumors. While other epothilones are currently under
      investigation, ixabepilone is the first epothilone B analogue approved by the
      U.S. Food and Drug Administration. Ixabepilone has been shown to have preclinical
      activity in chemotherapy-sensitive and chemotherapy-resistant tumor models, and
      synergistic antitumor activity with other chemotherapeutic and targeted agents.
      Single-agent ixabepilone has demonstrated clinical activity in multiple solid
      tumors including advanced breast, lung, prostate, pancreatic, renal cell, and
      ovarian cancers. Most notably, efficacy has been demonstrated in patients with
      metastatic breast cancer (MBC) progressing after treatment with anthracyclines
      and taxanes. A phase III trial in anthracycline- and taxane-resistant MBC showed
      superior disease control with ixabepilone plus capecitabine versus capecitabine
      monotherapy, resulting in its approval. Ixabepilone is also active in
      chemotherapy-naive and taxane-resistant hormone-refractory prostate cancer and
      platinum-resistant non-small cell lung cancer. Neutropenia and peripheral sensory
      neuropathy are the most common adverse events associated with treatment. This
      review discusses the challenges of MDR and the data that support the use of
      epothilones in this setting, focusing on ixabepilone.

PMID- 19088323
TI  - Effect of molecules secreted by Lactobacillus acidophilus strain La-5 on
      Escherichia coli O157:H7 colonization.
AB  - The probiotic bacterium Lactobacillus acidophilus strain La-5 is a gut-colonizing
      microorganism that, when established, becomes an important part of the
      gastrointestinal (GI) tract microbiota. It has been shown to be effective against
      enterohemorrhagic Escherichia coli (EHEC) O157:H7 infection. We have previously
      shown that molecules released by probiotic strain La-5 influence the
      transcription of EHEC genes involved in colonization and quorum sensing. In this
      work, we report on the ability of these molecules to prevent the adherence of
      EHEC to epithelial cells and on its capacity to concentrate F-actin at adhesion
      sites. With a fluorescein-labeled phallotoxin, it was shown that La-5 cell-free
      spent medium (CFSM) fractions remarkably reduced attaching and effacing lesions
      in HeLa cells. We also observed a significant inhibition of bacterial adhesion to
      Hep-2 cells when they were treated with the same La-5 CFSM fractions. In order to
      observe if La-5 CFSM fractions exhibited the same effect in vivo, we studied the
      ability of luminescent EHEC constructs (LEE1::luxCDABE) to adhere to intestinal
      epithelial cells of specific-pathogen-free ICR mice following intragastric
      inoculation. Colonization of the GI tract by luminescent EHEC O157:H7 was
      monitored in real time with a slow-scan charge-coupled device camera. At the same
      time, fecal shedding of EHEC was studied. Following oral gavage of the La-5
      active fraction, we observed a reduced amount of bioluminescence signal along
      with a decrease in fecal shedding by mice, indicating an effect on the ability of
      the organism to colonize the GI tract. Our results confirm past evidence of the
      possibility of blocking or interfering with EHEC's virulence by active molecules
      contained in the probiotic CFSM and identify novel therapeutic alternatives to
      antibiotic treatments in the fight against food-borne pathogens.

PMID- 19088325
TI  - Osteonecrosis of the jaw and the use of antiangiogenic agents: just an
      association?

PMID- 19088327
TI  - Serum adiponectin is associated with family history of diabetes independently of
      obesity and insulin resistance in healthy Korean men and women.
AB  - BACKGROUND: Adiponectin has been reported as a new risk factor for the
      development of diabetes. However, it is not clear whether adiponectin levels are
      associated with family history of diabetes (FHD). OBJECTIVE: The objective of
      this study was to measure the independent association of serum adiponectin with
      FHD in relation to insulin resistance and obesity. METHODS: In 2006, a cross
      sectional study was conducted in which waist circumference (WC), body mass index
      (BMI), and serum adiponectin were measured in 5919 healthy Korean men and women.
      Multiple linear regression models were used to assess the association of serum
      adiponectin levels with FHD. The population was classified into two groups
      according to median values for each of the following variables: WC, BMI, and
      homeostasis model assessment of insulin resistance (HOMA-IR). RESULTS: The
      positive FHD group had higher HOMA-IR and lower adiponectin levels in both men
      and women than those without FHD. Adiponectin levels were significantly
      associated with FHD in men and women respectively, after adjusting for age, BMI,
      and alcohol consumption (P=0.0123 and 0.0004). The relationship between
      adiponectin and FHD was similar between the high and low insulin resistance, BMI,
      and WC groups in male non-smokers and in all Korean women. CONCLUSION: These
      results confirm that adiponectin levels are associated with FHD. These data also
      suggest that the association of serum adiponectin with FHD may be independent of
      obesity and insulin resistance.

PMID- 19088328
TI  - Arabidopsis synaptotagmin1 maintains plasma membrane integrity.

PMID- 19088329
TI  - Arabidopsis synaptotagmin 1 is required for the maintenance of plasma membrane
      integrity and cell viability.
AB  - Plasma membrane repair in animal cells uses synaptotagmin 7, a Ca(2+)-activated
      membrane fusion protein that mediates delivery of intracellular membranes to
      wound sites by a mechanism resembling neuronal Ca(2+)-regulated exocytosis. Here,
      we show that loss of function of the homologous Arabidopsis thaliana
      Synaptotagmin 1 protein (SYT1) reduces the viability of cells as a consequence of
      a decrease in the integrity of the plasma membrane. This reduced integrity is
      enhanced in the syt1-2 null mutant in conditions of osmotic stress likely caused
      by a defective plasma membrane repair. Consistent with a role in plasma membrane
      repair, SYT1 is ubiquitously expressed, is located at the plasma membrane, and
      shares all domains characteristic of animal synaptotagmins (i.e., an N terminus
      transmembrane domain and a cytoplasmic region containing two C2 domains with
      phospholipid binding activities). Our analyses support that membrane trafficking
      mediated by SYT1 is important for plasma membrane integrity and plant fitness.

PMID- 19088330
TI  - Calcium-dependent freezing tolerance in Arabidopsis involves membrane resealing
      via synaptotagmin SYT1.
AB  - Plant freezing tolerance involves the prevention of lethal freeze-induced damage
      to the plasma membrane. We hypothesized that plant freezing tolerance involves
      membrane resealing, which, in animal cells, is accomplished by calcium-dependent
      exocytosis following mechanical disruption of the plasma membrane. In Arabidopsis
      thaliana protoplasts, extracellular calcium enhanced not only freezing tolerance
      but also tolerance to electroporation, which typically punctures the plasma
      membrane. However, calcium did not enhance survival when protoplasts were exposed
      to osmotic stress that mimicked freeze-induced dehydration. Calcium-dependent
      freezing tolerance was also detected with leaf sections in which ice crystals
      intruded into tissues. Interestingly, calcium-dependent freezing tolerance was
      inhibited by extracellular addition of an antibody against the cytosolic region
      of SYT1, a homolog of synaptotagmin known to be a calcium sensor that initiates
      exocytosis. This inhibition indicates that the puncture allowing the antibody to
      flow into the cytoplasm occurs during freeze/thawing. Thus, we propose that
      calcium-dependent freezing tolerance results from resealing of the punctured
      site. Protoplasts or leaf sections isolated from Arabidopsis SYT1-RNA
      interference (RNAi) plants lost calcium-dependent freezing tolerance, and intact
      SYT1-RNAi plants had lower freezing tolerance than control plants. Taken
      together, these findings suggest that calcium-dependent freezing tolerance
      results from membrane resealing and that this mechanism involves SYT1 function.

PMID- 19088331
TI  - ASYMMETRIC LEAVES2-LIKE19/LATERAL ORGAN BOUNDARIES DOMAIN30 and ASL20/LBD18
      regulate tracheary element differentiation in Arabidopsis.
AB  - ASYMMETRIC LEAVES2 (AS2)/LATERAL ORGAN BOUNDARIES DOMAIN (LBD) family proteins
      are plant-specific nuclear proteins, and genes encoding several family members
      have been implicated in plant development. We investigated the function of two
      members of the Arabidopsis thaliana AS2/LBD family, AS2-LIKE19 (ASL19)/LBD30 and
      ASL20/LBD18, which encode homologous proteins. Both ASL19 and ASL20 were
      expressed in immature tracheary elements (TEs), and the expression was dependent
      on VASCULAR-RELATED NAC-DOMAIN PROTEIN6 (VND6) and VND7, which are transcription
      factors required for TE differentiation. Overexpression of ASL19 and ASL20
      induced transdifferentiation of cells from nonvascular tissues into TE-like
      cells, similar to those induced upon VND6/7 overexpression. By contrast, aberrant
      TEs were formed when a cDNA encoding a fusion protein of ASL20 with an artificial
      repressor domain (ASL20-SRDX) was expressed from its native promoter. These
      results provide evidence that ASL proteins positively regulate TE
      differentiation. In transgenic plants overexpressing both ASL19 and ASL20, the
      xylem-deficient phenotype caused by the expression of dominant-negative versions
      of VND6/7 proteins was not rescued. However, ectopic expression of VND7 was
      detected in plants overexpressing ASL20. Moreover, VND genes and their downstream
      targets were downregulated in ASL20-SRDX plants. Therefore, ASL20 appears to be
      involved in a positive feedback loop for VND7 expression that regulates TE
      differentiation-related genes.

PMID- 19088332
TI  - Flavour compounds in tomato fruits: identification of loci and potential pathways
      affecting volatile composition.
AB  - The unique flavour of a tomato fruit is the sum of a complex interaction among
      sugars, acids, and a large set of volatile compounds. While it is generally
      acknowledged that the flavour of commercially produced tomatoes is inferior, the
      biochemical and genetic complexity of the trait has made breeding for improved
      flavour extremely difficult. The volatiles, in particular, present a major
      challenge for flavour improvement, being generated from a diverse set of lipid,
      amino acid, and carotenoid precursors. Very few genes controlling their
      biosynthesis have been identified. New quantitative trait loci (QTLs) that affect
      the volatile emissions of red-ripe fruits are described here. A population of
      introgression lines derived from a cross between the cultivated tomato Solanum
      lycopersicum and its wild relative, S. habrochaites, was characterized over
      multiple seasons and locations. A total of 30 QTLs affecting the emission of one
      or more volatiles were mapped. The data from this mapping project, combined with
      previously collected data on an IL population derived from a cross between S.
      lycopersicum and S. pennellii populations, were used to construct a correlational
      database. A metabolite tree derived from these data provides new insights into
      the pathways for the synthesis of several of these volatiles. One QTL is a novel
      locus affecting fruit carotenoid content on chromosome 2. Volatile emissions from
      this and other lines indicate that the linear and cyclic apocarotenoid volatiles
      are probably derived from separate carotenoid pools.

PMID- 19088333
TI  - Measurements of oxygen permeability coefficients of rice (Oryza sativa L.) roots
      using a new perfusion technique.
AB  - A new approach is described to analyse the barrier properties of the outer part
      of rice (Oryza sativa L.) roots towards oxygen. By using a root-sleeving O(2)
      electrode, radial oxygen loss at different distances from the root apex was
      measured and related to the corresponding root structure. In addition, internal
      oxygen concentrations were precisely adjusted using a newly developed perfusion
      technique. Thus, the oxygen permeability coefficient of the outer part of the
      root (OPR) could be calculated, since both (i) the oxygen flow across the OPR and
      (ii) the oxygen concentration gradient across the OPR from inside to outside were
      known. On the basis of the permeability coefficient, it can be decided whether or
      not different rates of oxygen loss across the OPR are due to changes in the OPR
      structure and/or to changes in the concentration gradient. The technique was
      applied to rice root segments, which enabled rapid perfusion of aerenchyma. In
      the present study, roots of rice grown under aerobic conditions were used which
      should have a higher O(2) permeability compared with that of plants grown in
      deoxygenated solution. Both radial oxygen losses and permeability coefficients
      decreased along the root, reaching the lowest values at the basal positions.
      Values of oxygen permeability coefficients of the OPR were corrected for external
      unstirred layers. They decreased from (2.8+/-0.2)x10(-6) m s(-1) at 30 mm to
      (1.1+/-0.2)x10(-6) m s(-1) at 60 mm from the apex (n=5; +/-SE). They were similar
      to those measured previously for cuticles. Low diffusional oxygen permeability of
      the OPR suggested that the barrier to radial oxygen loss was effective. This may
      help to retain oxygen within the root and enhance diffusion of oxygen towards the
      apex in the presence of a relatively high water permeability. The results are
      discussed in terms of the inter-relationship between the water and oxygen
      permeabilities as roots develop in either aerated or deoxygenated (stagnant)
      media.

PMID- 19088334
TI  - Influence of clavata3-2 mutation on early flower development in Arabidopsis
      thaliana: quantitative analysis of changing geometry.
AB  - Early development of the flower primordium has been studied in Arabidopsis
      thaliana clavata3-2 (clv3-2) plants with the aid of sequential in vivo replicas
      and longitudinal microtome sections. Sequential replicas show that, although
      there is no regular phyllotaxis in the clv3-2 inflorescence shoot apex, the sites
      of new primordium formation are, to a large extent, predictable. The primordium
      always appears in a wedge-like region of the meristem periphery flanked by two
      older primordia. In general, stages of primordium development in clv3-2 are
      similar to the wild type, but quantitative geometry analysis shows that the clv3
      2 primordium shape is affected even before the CLAVATA/WUSCHEL regulatory network
      would start to operate in the wild-type primordium. The shape of the youngest
      primordium in the mutant is more variable than in the wild type. In particular,
      the shape of the adaxial primordium boundary varies and seems to be related to
      the shape of the space available for the given primordium formation, suggesting
      that physical constraints play a significant role in primordium shape
      determination. The role of physical constraints is also manifested in that the
      shape of the primordium in the later stages, as well as the number and position
      of sepals, are adjusted to the available space. Longitudinal sections of clv3-2
      apices show that the shape of surface cells of the meristem and young primordium
      is different from the wild type. Moreover, there is only one tunica layer in both
      the meristem and in the primordium until it becomes a bulge that is distinctly
      separated from the meristem. Starting from this stage, the anticlinal divisions
      predominate in subprotodermal cells, suggesting that the distribution of
      periclinal and anticlinal cell divisions in the early development of the flower
      primordium is not directly affected by the clv3-2 mutation.

PMID- 19088335
TI  - Gating of aquaporins by light and reactive oxygen species in leaf parenchyma
      cells of the midrib of Zea mays.
AB  - Changes of the water permeability aquaporin (AQP) activity of leaf cells were
      investigated in response to different light regimes (low versus high). Using a
      cell pressure probe, hydraulic properties (half-time of water exchange, T(1/2)
      infinity 1/water permeability) of parenchyma cells in the midrib tissue of maize
      (Zea mays L.) leaves have been measured. A new perfusion technique was applied to
      excised leaves to keep turgor constant and to modify the environment around cells
      by perfusing solutions using a pressure chamber. In response to low light (LL) of
      200 micromol m(-2) s(-1), T(1/2) decreased during the perfusion of a control
      solution of 0.5 mM CaCl(2) by a factor of two. This was in line with earlier
      results from leaf cells of intact maize plants at a constant turgor. In contrast,
      high light (HL) at intensities of 800 micromol m(-2) s(-1) and 1800 micromol m(
      2) s(-1) increased the T(1/2) in two-thirds of cells by factors of 14 and 35,
      respectively. The effects of HL on T(1/2) were similar to those caused by
      H(2)O(2) treatment in the presence of Fe(2+), which produced *OH (Fenton
      reaction; reversible oxidative gating of aquaporins). Treatments with 20 mM
      H(2)O(2) following Fe(2+) pre-treatments increased the T(1/2) by a factor of 30.
      Those increased T(1/2) values could be partly recovered, either when the
      perfusion solution was changed back to the control solution or when LL was
      applied. 3mM of the antioxidant glutathione also reversed the effects of HL. The
      data suggest that HL could induce reactive oxygen species (ROS) such as *OH, and
      they affected water relations. The results provide evidence that the varying
      light climate adjusts water flow at the cell level; that is, water flow is
      maximized at a certain light intensity and then reduced again by HL. Light
      effects are discussed in terms of an oxidative gating of aquaporins by ROS.

PMID- 19088336
TI  - Thigmomorphogenesis: a complex plant response to mechano-stimulation.
AB  - In nature, plants are challenged with hurricane winds, monsoon rains, and
      herbivory attacks, in addition to many other harsh mechanical perturbations that
      can threaten plant survival. As a result, over many years of evolution, plants
      have developed very sensitive mechanisms through which they can perceive and
      respond to even subtle stimuli, like touch. Some plants respond behaviourally to
      the touch stimulus within seconds, while others show morphogenetic alterations
      over long periods of time, ranging from days to weeks. Various signalling
      molecules and phytohormones, including intracellular calcium, jasmonates,
      ethylene, abscisic acid, auxin, brassinosteroids, nitric oxide, and reactive
      oxygen species, have been implicated in touch responses. Many genes are induced
      following touch. These genes encode proteins involved in various cellular
      processes including calcium sensing, cell wall modifications, and defence. Twenty
      three per cent of these up-regulated genes contain a recently identified promoter
      element involved in the rapid induction in transcript levels following mechanical
      perturbations. The employment of various genetic, biochemical, and molecular
      tools may enable elucidation of the mechanisms through which plants perceive
      mechano-stimuli and transduce the signals intracellularly to induce appropriate
      responses.

PMID- 19088337
TI  - Molecular responses of Lotus japonicus to parasitism by the compatible species
      Orobanche aegyptiaca and the incompatible species Striga hermonthica.
AB  - Lotus japonicus genes responsive to parasitism by the compatible species
      Orobanche aegyptiaca and the incompatible species Striga hermonthica were
      isolated by using the suppression subtractive hybridization (SSH) strategy. O.
      aegyptiaca and S. hermonthica parasitism specifically induced the expression of
      genes involved in jasmonic acid (JA) biosynthesis and phytoalexin biosynthesis,
      respectively. Nodulation-related genes were almost exclusively found among the
      Orobanche-induced genes. Temporal gene expression analyses revealed that 19 out
      of the 48 Orobanche-induced genes and 5 out of the 48 Striga-induced genes were
      up-regulated at 1 dai. Four genes, including putative trypsin protease inhibitor
      genes, exhibited systemic up-regulation in the host plant parasitized by O.
      aegyptiaca. On the other hand, S. hermonthica attachment did not induce systemic
      gene expression.

PMID- 19088339
TI  - The cover. Winter.

PMID- 19088338
TI  - Specific functions of individual class III peroxidase genes.
AB  - In higher plants, class III peroxidases exist as large multigene families (e.g.
      73 genes in Arabidopsis thaliana). The diversity of processes catalysed by
      peroxidases as well as the large number of their genes suggests the possibility
      of a functional specialization of each isoform. In addition, the fact that
      peroxidase promoter sequences are very divergent and that protein sequences
      contain both highly conserved domains and variable regions supports this
      hypothesis. However, two difficulties are associated with the study of the
      function of specific peroxidase genes: (i) the modification of the expression of
      a single peroxidase gene often results in no visible mutant phenotype, because it
      is compensated by redundant genes; and (ii) peroxidases show low substrate
      specificity in vitro resulting in an unreliable indication of peroxidase specific
      activity unless complementary data are available. The generalization of molecular
      biology approaches such as whole transcriptome analysis and recombinant DNA
      combined with biochemical approaches provide unprecedented tools for overcoming
      these difficulties. This review highlights progress made with these new
      techniques for identifying the specific function of individual class III
      peroxidase genes taking as an example the model plant A. thaliana, as well as
      discussing some other plants.

PMID- 19088340
TI  - A piece of my mind. A testy experience.

PMID- 19088341
TI  - CDC panel recommends vaccine for smokers; reviews HPV safety data.

PMID- 19088342
TI  - Economics may play role in crowding, boarding in emergency departments.

PMID- 19088343
TI  - 1000 Genomes Project promises closer look at variation in human genome.

PMID- 19088344
TI  - Medical student enrollment is up but still falls short of meeting need.

PMID- 19088345
TI  - Tight glucose control in critically ill adults.

PMID- 19088346
TI  - Tight glucose control in critically ill adults.

PMID- 19088347
TI  - Tight glucose control in critically ill adults.

PMID- 19088348
TI  - Tight glucose control in critically ill adults.

PMID- 19088349
TI  - Arsenic exposure and diabetes mellitus in the United States.

PMID- 19088350
TI  - Measuring mental health in child soldiers.

PMID- 19088351
TI  - Effect of evidence-based feeding guidelines on mortality of critically ill
      adults: a cluster randomized controlled trial.
AB  - CONTEXT: Evidence demonstrates that providing nutritional support to intensive
      care unit (ICU) patients within 24 hours of ICU admission reduces mortality.
      However, early feeding is not universally practiced. Changing practice in complex
      multidisciplinary environments is difficult. Evidence supporting whether
      guidelines can improve ICU feeding practices and patient outcomes is
      contradictory. OBJECTIVE: To determine whether evidence-based feeding guidelines,
      implemented using a multifaceted practice change strategy, improve feeding
      practices and reduce mortality in ICU patients. DESIGN, SETTING, AND PATIENTS:
      Cluster randomized trial in ICUs of 27 community and tertiary hospitals in
      Australia and New Zealand. Between November 2003 and May 2004, 1118 critically
      ill adult patients expected to remain in the ICU longer than 2 days were
      enrolled. All participants completed the study. INTERVENTIONS: Intensive care
      units were randomly assigned to guideline or control groups. Guideline ICUs
      developed an evidence-based guideline using Browman's Clinical Practice Guideline
      Development Cycle. A practice-change strategy composed of 18 specific
      interventions, leveraged by educational outreach visits, was implemented in
      guideline ICUs. MAIN OUTCOME MEASURES: Hospital discharge mortality. Secondary
      outcomes included ICU and hospital length of stay, organ dysfunction, and feeding
      process measures. RESULTS: Guideline and control ICUs enrolled 561 and 557
      patients, respectively. Guideline ICUs fed patients earlier (0.75 vs 1.37 mean
      days to enteral nutrition start; difference, -0.62 [95% confidence interval {CI},
      -0.82 to -0.36]; P < .001 and 1.04 vs 1.40 mean days to parenteral nutrition
      start; difference, -0.35 [95% CI, -0.61 to -0.01]; P = .04) and achieved caloric
      goals more often (6.10 vs 5.02 mean days per 10 fed patient-days; difference,
      1.07 [95% CI, 0.12 to 2.22]; P = .03). Guideline and control ICUs did not differ
      with regard to hospital discharge mortality (28.9% vs 27.4%; difference, 1.4%
      [95% CI, -6.3% to 12.0%]; P = .75) or to hospital length of stay (24.2 vs 24.3
      days; difference, -0.08 [95% CI, -3.8 to 4.4]; P = .97) or ICU length of stay
      (9.1 vs 9.9 days; difference, -0.86 [95% CI, -2.6 to 1.3]; P = .42). CONCLUSIONS:
      Using a multifaceted practice change strategy, ICUs successfully developed and
      introduced an evidence-based nutritional support guideline that promoted earlier
      feeding and greater nutritional adequacy. However, use of the guideline did not
      improve clinical outcomes. Trial Registration anzctr.org.au Identifier:
      ACTRN12608000407392.

PMID- 19088352
TI  - Effect of a low-glycemic index or a high-cereal fiber diet on type 2 diabetes: a
      randomized trial.
AB  - CONTEXT: Clinical trials using antihyperglycemic medications to improve glycemic
      control have not demonstrated the anticipated cardiovascular benefits. Low
      glycemic index diets may improve both glycemic control and cardiovascular risk
      factors for patients with type 2 diabetes but debate over their effectiveness
      continues due to trial limitations. OBJECTIVE: To test the effects of low
      glycemic index diets on glycemic control and cardiovascular risk factors in
      patients with type 2 diabetes. DESIGN, SETTING, AND PARTICIPANTS: A randomized,
      parallel study design at a Canadian university hospital research center of 210
      participants with type 2 diabetes treated with antihyperglycemic medications who
      were recruited by newspaper advertisement and randomly assigned to receive 1 of 2
      diet treatments each for 6 months between September 16, 2004, and May 22, 2007.
      INTERVENTION: High-cereal fiber or low-glycemic index dietary advice. MAIN
      OUTCOME MEASURES: Absolute change in glycated hemoglobin A(1c) (HbA(1c)), with
      fasting blood glucose and cardiovascular disease risk factors as secondary
      measures. RESULTS: In the intention-to-treat analysis, HbA(1c) decreased by 
      0.18% absolute HbA(1c) units (95% confidence interval [CI], -0.29% to -0.07%) in
      the high-cereal fiber diet compared with -0.50% absolute HbA(1c) units (95% CI, 
      0.61% to -0.39%) in the low-glycemic index diet (P < .001). There was also an
      increase of high-density lipoprotein cholesterol in the low-glycemic index diet
      by 1.7 mg/dL (95% CI, 0.8-2.6 mg/dL) compared with a decrease of high-density
      lipoprotein cholesterol by -0.2 mg/dL (95% CI, -0.9 to 0.5 mg/dL) in the high
      cereal fiber diet (P = .005). The reduction in dietary glycemic index related
      positively to the reduction in HbA(1c) concentration (r = 0.35, P < .001) and
      negatively to the increase in high-density lipoprotein cholesterol (r = -0.19, P
      = .009). CONCLUSION: In patients with type 2 diabetes, 6-month treatment with a
      low-glycemic index diet resulted in moderately lower HbA(1c) levels compared with
      a high-cereal fiber diet. Trial Registration clinicaltrials.gov identifier:
      NCT00438698.

PMID- 19088354
TI  - Smoking and colorectal cancer: a meta-analysis.
AB  - CONTEXT: Colorectal cancer is the third most common form of cancer and the fourth
      most frequent cause of cancer deaths worldwide. The association between cigarette
      smoking and colorectal cancer has been inconsistent among studies. OBJECTIVE: To
      clarify the association of cigarette smoking and colorectal cancer, we performed
      a comprehensive literature search and a meta-analysis of observational studies
      considering both incidence and mortality. DATA SOURCES: We performed a literature
      search using PubMed, ISI Web of Science (Science Citation Index Expanded), and
      EMBASE to May 2008, with no restrictions. We also reviewed references from all
      retrieved articles. STUDY SELECTION: All articles that were independent and
      contained the minimum information necessary to estimate the colorectal cancer
      risk associated with cigarette smoking and a corresponding measure of
      uncertainty. DATA EXTRACTION: Articles were reviewed and data were extracted and
      cross-checked independently by 3 investigators, and any disagreement was resolved
      by consensus among all 3. RESULTS: One hundred six observational studies were
      included in the analysis of incidence. Twenty-six studies provided adjusted risk
      estimates for ever smokers vs never smokers, leading to a pooled relative risk of
      1.18 (95% confidence interval [CI], 1.11-1.25). Smoking was associated with an
      absolute risk increase of 10.8 cases per 100,000 person-years (95% CI, 7.9-13.6).
      We found a statistically significant dose-relationship with an increasing number
      of pack-years and cigarettes per day. However, the association was statistically
      significant only after 30 years of smoking. Seventeen cohort studies were
      included in the analysis of mortality. The pooled risk estimate for ever vs never
      smokers was 1.25 (95% CI, 1.14-1.37). Smoking was associated with an absolute
      risk increase of 6.0 deaths per 100,000 person-years (95% CI, 4.2-7.6). For both
      incidence and mortality, the association was stronger for cancer of the rectum
      than of the colon. CONCLUSION: Cigarette smoking is significantly associated with
      colorectal cancer incidence and mortality.

PMID- 19088355
TI  - Has this prepubertal girl been sexually abused?
AB  - CONTEXT: The legal and social sequelae of interpreting genital findings as
      indicative of sexual abuse are significant. While the absence of genital trauma
      does not rule out sexual abuse, the physical examination can identify genital
      findings compatible with sexual abuse. OBJECTIVES: To determine the diagnostic
      utility of the genital examination in prepubertal girls for identifying nonacute
      sexual abuse. DATA SOURCES: Published articles (1966-October 2008) that appeared
      in the MEDLINE database and were indexed under the search terms of child abuse,
      sexual or child abuse and either physical examination; genitalia; female,
      diagnosis; or sensitivity and specificity; and bibliographies of retrieved
      articles and textbooks. STUDY SELECTION: Three of the authors independently
      reviewed titles of articles obtained from MEDLINE and selected articles for full
      text review. DATA EXTRACTION: Two authors independently abstracted data to
      calculate sensitivity, specificity, and likelihood ratios for the diagnosis of
      nonacute genital trauma caused by sexual abuse in prepubertal girls. RESULTS:
      Data were not pooled due to study heterogeneity. The presence of vaginal
      discharge (positive likelihood ratio, 2.7; 95% confidence interval, 1.2-6.0)
      indicates an increased likelihood of sexual abuse. In the posterior hymen,
      hymenal transections, deep notches, and perforations prompt concerns for genital
      trauma from sexual abuse, but the sensitivity is unknown. Without a history of
      genital trauma from sexual abuse, the majority of prepubertal girls will not have
      a hymenal transection (specificity close to 100%). CONCLUSIONS: Vaginal discharge
      as well as posterior hymenal transections, deep notches, and perforations raise
      the suspicion for sexual abuse in a prepubertal girl, but the findings do not
      independently confirm the diagnosis. Given the broad 95% confidence intervals
      around the likelihood ratios for the presence of findings along with the low or
      unknown sensitivity of all physical examination findings evaluated, the physical
      examination cannot independently confirm or exclude nonacute sexual abuse as the
      cause of genital trauma in prepubertal girls.

PMID- 19088353
TI  - Long-term all-cause mortality in cancer patients with preexisting diabetes
      mellitus: a systematic review and meta-analysis.
AB  - CONTEXT: Diabetes mellitus appears to be a risk factor for some cancers, but the
      effect of preexisting diabetes on all-cause mortality in newly diagnosed cancer
      patients is less clear. OBJECTIVE: To perform a systematic review and meta
      analysis comparing overall survival in cancer patients with and without
      preexisting diabetes. DATA SOURCES: We searched MEDLINE and EMBASE through May
      15, 2008, including references of qualifying articles. STUDY SELECTION: English
      language, original investigations in humans with at least 3 months of follow-up
      were included. Titles, abstracts, and articles were reviewed by at least 2
      independent readers. Of 7858 titles identified in our original search, 48
      articles met our criteria. DATA EXTRACTION: One reviewer performed a full
      abstraction and other reviewers verified accuracy. We contacted authors and
      obtained additional information for 3 articles with insufficient reported data.
      RESULTS: Studies reporting cumulative survival rates were summarized
      qualitatively. Studies reporting Cox proportional hazard ratios (HRs) or Poisson
      relative risks were combined in a meta-analysis. A random-effects model meta
      analysis of 23 articles showed that diabetes was associated with an increased
      mortality HR of 1.41 (95% confidence interval [CI], 1.28-1.55) compared with
      normoglycemic individuals across all cancer types. Subgroup analyses by type of
      cancer showed increased risk for cancers of the endometrium (HR, 1.76; 95% CI,
      1.34-2.31), breast (HR, 1.61; 95% CI, 1.46-1.78), and colorectum (HR, 1.32; 95%
      CI, 1.24-1.41). CONCLUSIONS: Patients diagnosed with cancer who have preexisting
      diabetes are at increased risk for long-term, all-cause mortality compared with
      those without diabetes.

PMID- 19088356
TI  - Access to experimental drugs for terminally ill patients.

PMID- 19088357
TI  - Medicine discovers child abuse.

PMID- 19088358
TI  - Implementing nutrition guidelines in the critical care setting: a worthwhile and
      achievable goal?

PMID- 19088359
TI  - JAMA patient page. Colon cancer.

PMID- 19088360
TI  - A changing scenario in the clinical use of implantable defibrillators: the need
      for long-term data on lead performance.

PMID- 19088361
TI  - How anatomy can guide ablation in isthmic atrial flutter.

PMID- 19088362
TI  - Optimizing the treatment of atrial fibrillation: contributions by remote
      monitoring.

PMID- 19088363
TI  - Ibutilide revisited: stronger and safer than ever.

PMID- 19088364
TI  - A review of postural orthostatic tachycardia syndrome.
AB  - A 21-year-old female reports an 18-month history of light-headedness on standing.
      This is often associated with palpitations and a feeling of intense anxiety. She
      has had two black-outs in the past 12 months. She is not taking any regular
      medications. Her supine blood pressure was 126/84 mmHg with a heart rate of 76
      bpm, and her upright blood pressure was 122/80 mmHg with a heart rate of 114 bpm.
      A full system examination was otherwise normal. She had a 12-lead
      electrocardiogram performed which was unremarkable. She was referred for head-up
      tilt testing. She was symptomatic during the test and lost consciousness at 16
      min. Figure 1 summarizes her blood pressure and heart rate response to tilting. A
      diagnosis of postural orthostatic tachycardia syndrome with overlapping vasovagal
      syncope was made.

PMID- 19088365
TI  - A novel approach to syncopal patients: association analysis of polymorphisms in G
      protein genes and tilt outcome.
AB  - AIMS: G-proteins signal transduction pathways play a basic role in cardiovascular
      reflexes. We hypothesized that the predisposition to reflex-mediated syncope may
      be associated with genetic variations in G-protein genes. The aim of this study
      was to evaluate the effect of three single-nucleotide polymorphisms in G-protein
      genes on tilting outcome in syncopal patients. METHODS AND RESULTS: A total of
      217 syncopal patients free from any other disease were genotyped and examined
      related to tilting results. Genotyping was performed by polymerase chain reaction
      followed by restriction fragment length polymorphism in gene encoding the Gs
      protein alpha-subunit (polymorphism C393T), the G-protein beta 3 subunit--GNB3
      (polymorphism C825T)--and for the cardiac regulator of G-protein signalling RGS2
      (polymorphism C1114G). In multivariate logistic regression analysis, the
      homozygotes 825TT GNB3 (OR 0.37; 95% CI 0.14-0.97; P < 0.05) and body mass index
      (OR 0.87; 95% CI 0.78-0.97; P = 0.005) were independently associated with a lower
      chance of positive tilting results. No relationship was found between Vasovagal
      Syncope International Study type of syncope and the studied genotypes or the
      carriage of the polymorphic alleles. CONCLUSIONS: An association between tilting
      results and C825T GNB3 polymorphism in syncopal patients was found. The syncopal
      homozygotes 825TT GNB3 had a significantly lower chance of syncope during tilt
      testing.

PMID- 19088367
TI  - Stepping back to look forward.

PMID- 19088368
TI  - A new approach to menopausal therapy: the tissue selective estrogen complex.
AB  - A new approach to menopausal therapy is the tissue selective estrogen complex or
      the pairing of a selective estrogen receptor modulator with estrogens. The
      clinical profile of a tissue selective estrogen complex will result from the
      blended tissue-selective activities of its components. An appropriate tissue
      selective estrogen complex may provide the therapeutic benefits of estrogens and
      selective estrogen receptor modulators with better tolerability and safety than
      either therapy alone. An ideal menopausal therapy would reduce the number and
      severity of hot flashes, effectively treat vulvar-vaginal atrophy and its
      symptoms, prevent and treat menopausal osteoporosis, and have favorable effects
      on lipoprotein profiles, while at the same time would not stimulate the
      endometrium, not cause uterine bleeding, not increase the risk of vascular
      events, not be associated with breast pain or tenderness, and potentially reduce
      breast cancer incidence. Here, we introduce the concept of a tissue selective
      estrogen complex and the rationale for its development as a next generation
      menopausal therapy.

PMID- 19088370
TI  - Arsenic trioxide (As2O3) inhibits expression of estrogen receptor-alpha through
      regulation of the mitogen-activated protein kinase (MAPK) pathway in endometrial
      cancer cells.
AB  - Given that prolonged exposure to unopposed estrogen has been implicated in
      endometrial carcinogenesis, our goal was to evaluate the effect of As(2)O(3) on
      regulation of estrogen receptor-alpha (ERa) expression in endometrial cancer
      cells. As(2)O(3) inhibited ER- mRNA and protein expression in a dose-dependent
      manner in both the Ishikawa and ECC-1 endometrial cancer cell lines. Treatment
      with As(2)O(3) resulted in rapid phosphorylation of the p42/p44 MAPK which could
      be abolished by addition of the MAPK inhibitor, U0126. Although treatment with
      U0126 alone resulted in up-regulation of ER- mRNA and protein, exposure to U0126
      in combination with As(2)O(3) counteracted As(2)O(3)'s inhibitory effect on ER-
      expression. We provide evidence that As(2)O(3) inhibits ER- mRNA and protein
      expression in endometrial cancer cells, potentially through interaction with the
      MAPK pathway. Thus, As(2)O(3) may be valuable for its anti-estrogenic activity in
      combination with its anti-tumorigenic effects and be a novel therapeutic agent
      for endometrial cancer.

PMID- 19088369
TI  - The expression and ovarian steroid regulation of endometrial micro-RNAs.
AB  - MicroRNAs (miRNAs) which regulate gene expression stability displayed an aberrant
      expression profile in ectopic endometrium (ECE) as compared to eutopic (EUE) and
      normal endometrium (NE). We assessed the expression of miR-17-5p, miR-23a, miR
      23b and miR-542-3p, their predicted target genes, steroidogenic acute regulatory
      protein, aromatase and cyclooxygenase-2, and influence of ovarian steroids on
      their expression in endometrial stromal (ESC) and glandular epithelial cells
      (GEC). The results indicated a lower expression of miR-23b and miR-542-3p and
      higher level of miR-17-5p in paired ECE and EUE as compared with NE. These levels
      were elevated and inversely correlated with the level of expression of their
      respective target genes in ECE. The expression of these miRNAs and genes was
      differentially regulated by 17beta- estradiol, medroxyprogesterone acetate, ICI
      182780 and RU-486, or their respective combinations in ESC and GEC. We concluded
      that altered expression of specific miRNAs in ECE, affecting the stability of
      their target genes expression, has direct implications in pathogenesis of
      endometriosis.

PMID- 19088371
TI  - Endoglin (CD105) expression in the human heart throughout gestation: an
      immunohistochemical study.
AB  - Endoglin is an 180 KDa protein which plays an important role in the vascular
      system and cardiac embryogenesis. Indeed, monoallelic mutations in the endoglin
      gene are associated with the development of hereditary hemorrhagic telangiectasia
      type 1; moreover endoglin knockout mice die precociously because of severe
      arteriovenous and cardiac malformations. In this study, endoglin
      immunohistochemical expression was analyzed in the heart of 23 fetuses (9-38
      weeks), 5 of which displayed cardiac malformations, as well as in cardiac samples
      from 4 preterm and 1 term infants. At the ninth week, endoglin expression was
      recorded in the endocardium; it extended into the epicardial and myocardial
      vessels by the 10th week. This pattern was maintained throughout gestation in
      most fetuses, but not in those with cardiac malformations. Endoglin expression up
      to term gestation indicates that its role in human heart development is not
      limited to the early gestation. Endoglin altered expression in association with
      cardiac defects further highlights its importance in normal cardiac embryogenesis
      and morphogenesis.

PMID- 19088372
TI  - Developmental potential of human oocytes after slow freezing or vitrification: a
      randomized in vitro study based on parthenogenesis.
AB  - The aim of the this study was to compare the in vitro developmental competence of
      parthenogenetically activated oocytes cryopreserved with slow-freezing or
      vitrification. Supernumerary metaphase II oocytes obtained during in vitro
      fertilization procedures were randomized to slow freezing or vitrification
      procedure. After thawing or devitrification, oocytes were parthenogenetically
      activated and cultured. Survival, activation, development rate, and cell number
      during culture were compared. The 2 groups showed no significant differences
      between the rates of parthenogenetic activation, development, good quality
      parthenotes and blastomere number on day 2 of culture. However, parthenotes from
      the devitrified oocytes continued cleaving till day 3 in a significantly low
      proportion (27% vs. 42%). On day 3, the mean number of blastomeres was also lower
      in vitrification group compared to slow-freezing (4.8 + 1.9 vs. 5.8 + 1.7). In
      conclusion, parthenogenesis highlights a reduced potential of vitrified oocytes
      to cleave on day 3 compared with oocytes from slow-freezing.

PMID- 19088373
TI  - Altered expression of regulators of caspase activity within trophoblast of normal
      pregnancies and pregnancies complicated by preeclampsia.
AB  - Apoptosis within villous trophoblast is increased in pregnancies complicated by
      pre-eclampsia (PE). Caspase activity is regulated by the balance of inhibitors of
      apoptosis proteins (IAPs). This study investigated the expression and
      localisation of smac, HtrA2/Omi and IAPs in villous trophoblast in normal
      pregnancies and those complicated by PE. smac was significantly elevated in PE
      compared to normal pregnancies and staining was evident in syncytiotrophoblast
      (ST), cytotrophoblast (CT) and endothelial cells. Weak staining for HtrA2/Omi was
      present in ST cytoplasm in both normal and PE pregnancies. XIAP and survivin were
      not altered in PE. XIAP localized to ST cytoplasm, with weak staining in CT.
      Survivin localized to ST and CT cytoplasm, but also CT nuclei. In non-placental
      cells increased smac expression in the presence of normal IAP expression induces
      apoptosis. In conclusion, the increased expression of smac in villous trophoblast
      may have a role in increased apoptosis in PE.

PMID- 19088374
TI  - Unidirectional transport across cultured ovine amniotic epithelial cell
      monolayer.
AB  - OBJECTIVE: To determine whether ovine amniotic cells in monolayer culture exhibit
      unidirectional transport. METHODS: Permeability of (14)C-inulin was measured in
      two directions across ovine amniotic cells grown to confluence on cell culture
      inserts. RESULTS: Permeability was 0.69 + 0.17 (SE) microl/min/cm(2) from the top
      of the insert where the cells were attached to the bottom and 0.11 + 0.02
      microl/min/cm(2) in the reverse direction (P < 0.001). Permeability was similar
      in the two directions for chorionic cells and umbilical vein endothelial cells.
      Addition of vascular endothelial growth factor did not alter permeability.
      CONCLUSIONS: Transcellular transport in ovine amniotic monolayers is
      directionally specific. The transport ratio of 6.2:1 for (14)C-inulin is
      comparable to the in vivo ratio of 4.7:1 for the ovine intramembranous pathway
      and is consistent with passive diffusion in both directions and vesicular
      transport in one direction across the monolayer at 5.2 times the rate of passive
      diffusion.

PMID- 19088375
TI  - Concentrations of receptor for advanced glycation end products, VEGF and CML in
      plasma, follicular fluid, and peritoneal fluid in women with and without
      endometriosis.
AB  - The etiology and pathogenesis of endometriosis is largely unknown. It has been
      reported that advanced glycation end products-receptor for advanced glycation end
      products regulation relates to oxidative stress, inflammatory reaction,
      apoptosis, and angiogenesis through vascular endothelial growth factor
      activation. The purpose of this study was to examine whether advanced glycation
      end products-receptor for advanced glycation end products regulation contributes
      to the pathogenesis of endometriosis. Plasma, follicular, and peritoneal fluid
      samples were collected from women with or without endometriosis, and soluble
      receptor for advanced glycation end products, vascular endothelial growth factor
      and carboxymethyl lysine levels were measured by enzyme-linked immunosorbent
      assay. Vascular endothelial growth factor and soluble receptor for advanced
      glycation end products concentrations were similar in plasma; however, their
      concentrations in follicular fluid were significantly increased in endometriosis
      patients (soluble receptor for advanced glycation end products was 132 + 31 pg/mg
      of protein vs. 105 + 27 pg/mg; vascular endothelial growth factor was 70 + 3
      pg/mg vs. 49 + 18 pg/mg, expressed as the mean + standard deviation). Increased
      soluble receptor for advanced glycation end products and vascular endothelial
      growth factor levels in a local environment suggest that the advanced glycation
      end products-receptor for advanced glycation end products may contribute to the
      pathogenesis of endometriosis.

PMID- 19088376
TI  - Venous thromboembolism in patients with acute leukemia: incidence, risk factors,
      and effect on survival.
AB  - A population-based cohort was used to determine the incidence and risk factors
      associated with development of venous thromboembolism (VTE) among Californians
      diagnosed with acute leukemia between 1993 to 1999. Principal outcomes were deep
      vein thrombosis in both the lower and upper extremities, pulmonary embolism, and
      mortality. Among 5394 cases with acute myelogenous leukemia (AML), the 2-year
      cumulative incidence of VTE was 281 (5.2%). Sixty-four percent of the VTE events
      occurred within 3 months of AML diagnosis. In AML patients, female sex, older
      age, number of chronic comorbidities, and presence of a catheter were significant
      predictors of development of VTE within 1 year. A diagnosis of VTE was not
      associated with reduced survival in AML patients. Among 2482 cases with acute
      lymphoblastic leukemia (ALL), the 2-year incidence of VTE in ALL was 4.5%. Risk
      factors for VTE were presence of a central venous catheter, older age, and number
      of chronic comorbidities. In the patients with ALL, development of VTE was
      associated with a 40% increase in the risk of dying within 1 year. The incidence
      of VTE in acute leukemia is appreciable, and is comparable with the incidence in
      many solid tumors.

PMID- 19088377
TI  - Rac GTPases play critical roles in early T-cell development.
AB  - The Rac1 and Rac2 GTPases play important roles in many processes including
      cytoskeletal reorganization, proliferation, and survival, and are required for B
      cell development. Previous studies had shown that deficiency in Rac2 did not
      affect T-cell development, whereas the function of Rac1 in this process has not
      been investigated. We now show that simultaneous absence of both GTPases resulted
      in a very strong developmental block at the pre-TCR checkpoint and in defective
      positive selection. Unexpectedly, deficiency of Rac1 and Rac2 also resulted in
      the aberrant survival of thymocytes lacking expression of TCR beta, showing
      hallmarks of hyperactive Notch signaling. Furthermore, we found a similar novel
      phenotype in the absence of Vav1, Vav2, and Vav3, which function as guanine
      nucleotide exchange factors for Rac1 and Rac2. These results show that a pathway
      containing Vav and Rac proteins may negatively regulate Notch signaling during
      early thymic development.

PMID- 19088379
TI  - Intracellular cotrafficking of factor VIII and von Willebrand factor type 2N
      variants to storage organelles.
AB  - Weibel-Palade bodies (WPBs) are the endothelial storage organelles that are
      formed upon von Willebrand factor (VWF) expression. Apart from VWF, WPBs contain
      a variety of hemostatic and inflammatory proteins. Some of these are thought to
      be targeted to WPBs by directly interacting with VWF in the secretory pathway.
      Previous studies have demonstrated that coexpression of factor VIII (FVIII) with
      VWF results in costorage of both proteins. However, whether cotrafficking is
      driven by intracellular FVIII-VWF assembly has remained unclear. We now have
      addressed this issue using recombinant VWF type 2N variants that are known to
      display reduced FVIII binding in the circulation. Binding studies using purified
      fluorescent FVIII and VWF type 2N variants revealed FVIII binding defects varying
      from moderate (Arg854Gln, Cys1060Arg) to severe (Arg763Gly, Thr791Met,
      Arg816Trp). Upon expression in HEK293 cells, all VWF variants induced formation
      of WPB-like organelles that were able to recruit P-selectin, as well as FVIII.
      WPBs containing FVIII did not display their typical elongated shape, suggesting
      that FVIII affects the organization of VWF tubules therein. The finding that VWF
      type 2N variants are still capable of cotargeting FVIII to storage granules
      implies that trafficking of WPB cargo proteins does not necessarily require high
      affinity assembly with VWF.

PMID- 19088378
TI  - VEGF-mediated cross-talk within the neonatal murine thymus.
AB  - Although the mechanisms of cross-talk that regulate the hematopoietic and
      epithelial compartments of the thymus are well established, the interactions of
      these compartments with the thymic endothelium have been largely ignored. Current
      understanding of the thymic vasculature is based on studies of adult thymus. We
      show that the neonatal period represents a unique phase of thymic growth and
      differentiation, marked by endothelium that is organized as primitive, dense
      networks of capillaries dependent on vascular endothelial growth factor (VEGF).
      VEGF dependence in neonates is mediated by significantly higher levels of both
      VEGF production and endothelial VEGF receptor 2 (VEGF-R2) expression than in the
      adult thymus. VEGF is expressed locally in the neonatal thymus by immature, CD4(
      )CD8(-) "double negative" (DN) thymocytes and thymic epithelium. Relative to
      adult thymus, the neonatal thymus has greater thymocyte proliferation, and a
      predominance of immature thymocytes and cortical thymic epithelial cells (cTECs).
      Inhibition of VEGF signaling during the neonatal period results in rapid loss of
      the dense capillaries in the thymus and a marked reduction in the number of
      thymocytes. These data demonstrate that, during the early postnatal period, VEGF
      mediates cross-talk between the thymocyte and endothelial compartments of the
      thymus.

PMID- 19088380
TI  - Selection on cis-regulatory variation at B4galnt2 and its influence on von
      Willebrand factor in house mice.
AB  - The RIIIS/J inbred mouse strain is a model for type 1 von Willebrand disease
      (VWD), a common human bleeding disorder. Low von Willebrand factor (VWF) levels
      in RIIIS/J are due to a regulatory mutation, Mvwf1, which directs a tissue
      specific switch in expression of a glycosyltransferase, B4GALNT2, from intestine
      to blood vessel. We recently found that Mvwf1 lies on a founder allele common
      among laboratory mouse strains. To investigate the evolutionary forces operating
      at B4galnt2, we conducted a survey of DNA sequence polymorphism and
      microsatellite variation spanning the B4galnt2 gene region in natural Mus
      musculus domesticus populations. Two divergent haplotypes segregate in these
      natural populations, one of which corresponds to the RIIIS/J sequence. Different
      local populations display dramatic differences in the frequency of these
      haplotypes, and reduced microsatellite variability near B4galnt2 within the
      RIIIS/J haplotype is consistent with the recent action of natural selection. The
      level and pattern of DNA sequence polymorphism in the 5' flanking region of the
      gene significantly deviates from the neutral expectation and suggests that
      variation in B4galnt2 expression may be under balancing selection and/or arose
      from a recently introgressed allele that subsequently increased in frequency due
      to natural selection. However, coalescent simulations indicate that the
      heterogeneity in divergence between haplotypes is greater than expected under an
      introgression model. Analysis of a population where the RIIIS/J haplotype is in
      high frequency reveals an association between this haplotype, the B4galnt2 tissue
      specific switch, and a significant decrease in plasma VWF levels. Given these
      observations, we propose that low VWF levels may represent a fitness cost that is
      offset by a yet unknown benefit of the B4galnt2 tissue-specific switch. Similar
      mechanisms may account for the variability in VWF levels and high prevalence of
      VWD in other mammals, including humans.

PMID- 19088381
TI  - Blocking pore-open mutants of CLC-0 by amphiphilic blockers.
AB  - The blockade of CLC-0 chloride channels by p-chlorophenoxy acetate (CPA) has been
      thought to be state dependent; the conformational change of the channel pore
      during the "fast gating" alters the CPA binding affinity. Here, we examine the
      mechanism of CPA blocking in pore-open mutants of CLC-0 in which the residue E166
      was replaced by various amino acids. We find that the CPA-blocking affinities
      depend upon the volume and the hydrophobicity of the side chain of the introduced
      residue; CPA affinity can vary by three orders of magnitude in these mutants. On
      the other hand, mutations at the intracellular pore entrance, although affecting
      the association and dissociation rates of the CPA block, generate only a modest
      effect on the steady-state blocking affinity. In addition, various amphiphilic
      compounds, including fatty acids and alkyl sulfonates, can also block the pore
      open mutants of CLC-0 through a similar mechanism. The blocking affinity of fatty
      acids and alkyl sulfonates increases with the length of these amphiphilic
      blockers, a phenomenon similar to the block of the Shaker K(+) channel by long
      chain quaternary ammonium (QA) ions. These observations lead us to propose that
      the CPA block of the open pore of CLC-0 is similar to the blockade of voltage
      gated K(+) channels by long-chain QAs or by the inactivation ball peptide: the
      blocker first uses the hydrophilic end to "dock" at the pore entrance, and the
      hydrophobic part of the blocker then enters the pore to interact with a more
      hydrophobic region of the pore. This blocking mechanism appears to be very
      general because the block does not require a precise structural fit between the
      blocker and the pore, and the blocking mechanism applies to the cation and anion
      channels with unrelated pore architectures.

PMID- 19088382
TI  - Amphiphilic blockers punch through a mutant CLC-0 pore.
AB  - Intracellularly applied amphiphilic molecules, such as p-chlorophenoxy acetate
      (CPA) and octanoate, block various pore-open mutants of CLC-0. The voltage
      dependent block of a particular pore-open mutant, E166G, was found to be
      multiphasic. In symmetrical 140 mM Cl(-), the apparent affinity of the blocker in
      this mutant increased with a negative membrane potential but, paradoxically,
      decreased when the negative membrane potential was greater than -80 mV, a
      phenomenon similar to the blocker "punch-through" shown in many blocker studies
      of cation channels. To provide further evidence of the punch-through of CPA and
      octanoate, we studied the dissociation rate of the blocker from the pore by
      measuring the time constant of relief from the block under various voltage and
      ionic conditions. Consistent with the voltage dependence of the effect on the
      steady-state current, the rate of CPA dissociation from the E166G pore reached a
      minimum at -80 mV in symmetrical 140 mM Cl(-), and the direction of current
      recovery suggested that the bound CPA in the pore can dissociate into both
      intracellular and extracellular solutions. Moreover, the CPA dissociation depends
      upon the Cl(-) reversal potential with a minimal dissociation rate at a voltage
      80 mV more negative than the Cl(-) reversal potential. That the shift of the CPA
      dissociation rate follows the Cl(-) gradient across the membrane argues that
      these blockers can indeed punch through the channel pore. Furthermore, a minimal
      CPA-dissociation rate at a voltage 80 mV more negative than the Cl(-) reversal
      potential suggests that the outward blocker movement through the CLC-0 pore is
      more difficult than the inward movement.

PMID- 19088383
TI  - Identification of regulatory phosphorylation sites in a cell volume- and Ste20
      kinase-dependent ClC anion channel.
AB  - Changes in phosphorylation regulate the activity of various ClC anion transport
      proteins. However, the physiological context under which such regulation occurs
      and the signaling cascades that mediate phosphorylation are poorly understood. We
      have exploited the genetic model organism Caenorhabditis elegans to characterize
      ClC regulatory mechanisms and signaling networks. CLH-3b is a ClC anion channel
      that is expressed in the worm oocyte and excretory cell. Channel activation
      occurs in response to oocyte meiotic maturation and swelling via serine/threonine
      dephosphorylation mediated by the type I phosphatases GLC-7alpha and GLC-7beta. A
      Ste20 kinase, germinal center kinase (GCK)-3, binds to the cytoplasmic C terminus
      of CLH-3b and inhibits channel activity in a phosphorylation-dependent manner.
      Analysis of hyperpolarization-induced activation kinetics suggests that
      phosphorylation may inhibit the ClC fast gating mechanism. GCK-3 is an ortholog
      of mammalian SPAK and OSR1, kinases that bind to, phosphorylate, and regulate the
      cell volume-dependent activity of mammalian cation-Cl(-) cotransporters. Using
      mass spectrometry and patch clamp electrophysiology, we demonstrate here that CLH
      3b is a target of regulatory phosphorylation. Concomitant phosphorylation of S742
      and S747, which are located 70 and 75 amino acids downstream from the GCK-3
      binding site, are required for kinase-mediated channel inhibition. In contrast,
      swelling-induced channel activation occurs with dephosphorylation of S747 alone.
      Replacement of both S742 and S747 with glutamate gives rise to kinase- and
      swelling-insensitive channels that exhibit activity and biophysical properties
      similar to those of wild-type CLH-3b inhibited by GCK-3. Our studies provide
      novel insights into ClC regulation and mechanisms of cell volume signaling, and
      provide the foundation for studies aimed at defining how conformational changes
      in the cytoplasmic C terminus alter ClC gating and function in response to
      intracellular signaling events.

PMID- 19088385
TI  - Modelling optical scattering artefacts for varying pathlength in a gel dosimeter
      phantom.
AB  - A gelatin phantom containing an optically scattering funnel-shaped region of
      elevated optical density (OD) was used to examine light-scattering-induced
      artefacts in a cone-beam optical CT scanner used for gel dosimetry. To simulate
      polymer gel dosimeters, the opacity was introduced by adding a colloidal
      scatterer to the gelatin. Scatter results in an underestimate of OD (hence dose).
      In line profiles of OD taken from 3D reconstructions of the funnel, those
      profiles with a long pathlength through high OD regions exhibited a 'dishing' (or
      'cupping') artefact, while those of short pathlength exhibited the opposite
      effect-'doming'. These phenomena are accounted for by a model that includes the
      effect of stray, scattered light.

PMID- 19088384
TI  - Local anesthetics disrupt energetic coupling between the voltage-sensing segments
      of a sodium channel.
AB  - Local anesthetics block sodium channels in a state-dependent fashion, binding
      with higher affinity to open and/or inactivated states. Gating current
      measurements show that local anesthetics immobilize a fraction of the gating
      charge, suggesting that the movement of voltage sensors is modified when a local
      anesthetic binds to the pore of the sodium channel. Here, using voltage clamp
      fluorescence measurements, we provide a quantitative description of the effect of
      local anesthetics on the steady-state behavior of the voltage-sensing segments of
      a sodium channel. Lidocaine and QX-314 shifted the midpoints of the fluorescence
      voltage (F-V) curves of S4 domain III in the hyperpolarizing direction by 57 and
      65 mV, respectively. A single mutation in the S6 of domain IV (F1579A), a site
      critical for local anesthetic block, abolished the effect of QX-314 on the
      voltage sensor of domain III. Both local anesthetics modestly shifted the F-V
      relationships of S4 domain IV toward hyperpolarized potentials. In contrast, the
      F-V curve of the S4 domain I was shifted by 11 mV in the depolarizing direction
      upon QX-314 binding. These antagonistic effects of the local anesthetic indicate
      that the drug modifies the coupling between the voltage-sensing domains of the
      sodium channel. Our findings suggest a novel role of local anesthetics in
      modulating the gating apparatus of the sodium channel.

PMID- 19088386
TI  - The use of CT density changes at internal tissue interfaces to correlate internal
      organ motion with an external surrogate.
AB  - The purpose of this paper is to describe a non-invasive method to monitor the
      motion of internal organs affected by respiration without using external markers
      or spirometry, to test the correlation with external markers, and to calculate
      any time shift between the datasets. Ten lung cancer patients were CT scanned
      with a GE LightSpeed Plus 4-Slice CT scanner operating in a cine mode. We
      retrospectively reconstructed the raw CT data to obtain consecutive 0.5 s
      reconstructions at 0.1 s intervals to increase image sampling. We defined regions
      of interest containing tissue interfaces, including tumour/lung interfaces that
      move due to breathing on multiple axial slices and measured the mean CT number
      versus respiratory phase. Tumour motion was directly correlated with external
      marker motion, acquired simultaneously, using the sample coefficient of
      determination, r(2). Only three of the ten patients showed correlation higher
      than r(2) = 0.80 between tumour motion and external marker position. However,
      after taking into account time shifts (ranging between 0 s and 0.4 s) between the
      two data sets, all ten patients showed correlation better than r(2) = 0.8. This
      non-invasive method for monitoring the motion of internal organs is an effective
      tool that can assess the use of external markers for 4D-CT imaging and
      respiratory-gated radiotherapy on a patient-specific basis.

PMID- 19088387
TI  - Multi-pinhole collimator design for small-object imaging with SiliSPECT: a high
      resolution SPECT.
AB  - We have designed a multi-pinhole collimator for a dual-headed, stationary SPECT
      system that incorporates high-resolution silicon double-sided strip detectors.
      The compact camera design of our system enables imaging at source-collimator
      distances between 20 and 30 mm. Our analytical calculations show that using knife
      edge pinholes with small-opening angles or cylindrically shaped pinholes in a
      focused, multi-pinhole configuration in combination with this camera geometry can
      generate narrow sensitivity profiles across the field of view that can be useful
      for imaging small objects at high sensitivity and resolution. The current
      prototype system uses two collimators each containing 127 cylindrically shaped
      pinholes that are focused toward a target volume. Our goal is imaging objects
      such as a mouse brain, which could find potential applications in molecular
      imaging.

PMID- 19088388
TI  - Predicting the clonogenic survival of A549 cells after modulated x-ray
      irradiation using the linear quadratic model.
AB  - In this study we present two prediction methods, mean dose and summed dose, for
      predicting the number of A549 cells that will survive after modulated x-ray
      irradiation. The prediction methods incorporate the dose profile from the
      modulated x-ray fluence map applied across the cell sample and the linear
      quadratic (LQ) model. We investigated the clonogenic survival of A549 cells when
      irradiated using two different modulated x-ray fluence maps. Differences between
      the measured and predicted surviving fraction were observed for modulated x-ray
      irradiation. When the x-ray fluence map produced a steep dose gradient across the
      sample, fewer cells survived in the unirradiated region than expected. When the x
      ray fluence map produced a less steep dose gradient across the sample, more cells
      survived in the unirradiated region than expected. Regardless of the steepness of
      the dose gradient, more cells survived in the irradiated region than expected for
      the reference dose range of 1-10 Gy. The change in the cell survival for the
      unirradiated regions of the two different dose gradients may be an important
      factor to consider when predicting the number of cells that will survive at the
      edge of modulated x-ray fields. This investigation provides an improved method of
      predicting cell survival for modulated x-ray radiation treatment. It highlights
      the limitations of the LQ model, particularly in its ability to describe the
      biological response of cells irradiated under these conditions.

PMID- 19088389
TI  - Comparison of two dedicated 'in beam' PET systems via simultaneous imaging of
      (12)C-induced beta(+)-activity.
AB  - The selective energy deposition of hadrontherapy has led to a growing interest in
      quality assurance techniques such as 'in-beam' PET. Due to the current lack of
      commercial solutions, dedicated detectors need to be developed. In this paper, we
      compare the performances of two different 'in-beam' PET systems which were
      simultaneously operated during and after low energy carbon ion irradiation of
      PMMA phantoms at GSI Darmstadt. The results highlight advantages and drawbacks of
      a novel in-beam PET prototype against a long-term clinically operated tomograph
      for ion therapy monitoring.

PMID- 19088390
TI  - Variation of the dielectric properties of tissues with age: the effect on the
      values of SAR in children when exposed to walkie-talkie devices.
AB  - In vitro dielectric properties of ageing porcine tissues were measured in the
      frequency range of 50 MHz-20 GHz, and the total combined uncertainties of the
      measurements were assessed. The results show statistically significant reduction
      with age in both permittivity and conductivity of 10 out of 15 measured tissues.
      At microwave frequencies, the observed variations are mainly due to the reduction
      in the water content of tissues as an animal ages. The results obtained were then
      used to calculate the SAR values in children of age 3 and 7 years when they are
      exposed to RF induced by walkie-talkie devices. No significant differences
      between the SAR values for the children of either age or for adults were
      observed.

PMID- 19088391
TI  - Magnetic field effects on the energy deposition spectra of MV photon radiation.
AB  - Several groups worldwide have proposed various concepts for improving megavoltage
      (MV) radiotherapy that involve irradiating patients in the presence of a magnetic
      field-either for image guidance in the case of hybrid radiotherapy-MRI machines
      or for purposes of introducing tighter control over dose distributions. The
      presence of a magnetic field alters the trajectory of charged particles between
      interactions with the medium and thus has the potential to alter energy
      deposition patterns within a sub-cellular target volume. In this work, we use the
      MC radiation transport code PENELOPE with appropriate algorithms invoked to
      incorporate magnetic field deflections to investigate electron energy fluence in
      the presence of a uniform magnetic field and the energy deposition spectra within
      a 10 microm water sphere as a function of magnetic field strength. The
      simulations suggest only very minor changes to the electron fluence even for
      extremely strong magnetic fields. Further, calculations of the dose-averaged
      lineal energy indicate that a magnetic field strength of at least 70 T is
      required before beam quality will change by more than 2%.

PMID- 19088392
TI  - Exploring neuro-vascular and neuro-metabolic coupling in rat somatosensory
      cortex.
AB  - The existence of a coupling between changes in neuronal activity, cerebral blood
      flow and blood oxygenation is well known. The explicit relationship between these
      systems, however, is complex and remains a subject of intense research. Here, we
      use direct electrophysiological recordings to predict blood flow and oxygenation
      changes measured with optical methods during parametric stimulation applied to
      the somatosensory cortex in rat brain. Using a multimodal model of the cerebral
      functional unit, we estimate a neuro-vascular and a neuro-metabolic transfer
      function relating the experimentally measured neural responses with the inputs to
      a vascular model predicting hemodynamic and blood oxygenation changes. We show
      that our model can accurately predict experimentally measured parametric
      hemodynamic evoked responses by using a single linear transfer function
      relationship with a reduced number of state parameters to relate the level of
      neural activity to evoked cerebral blood flow and oxygen metabolism changes. At
      the same time, we characterize the metabolic and vascular neural response
      functions and interpret their physiological significance.

PMID- 19088393
TI  - A pseudo-dynamic sub-optimal filter for elastography under static loading and
      measurements.
AB  - We propose a pseudo-dynamic form of a sub-optimal Kalman filter for elastography
      of plane-strain models of soft tissues under strictly static deformations and
      partial measurements. Since the tissue material is nearly incompressible and is
      thus prone to volumetric locking via standard displacement-based finite element
      formulations, we use a Cosserat point approach for deriving the static
      equilibrium equations. A pseudo-dynamical form of the equilibrium equations, with
      added noise and appropriate augmentation by the discretized shear modulus as
      additional states, is then adopted as the process equation such that its steady
      state solution approaches the static response of the plane-strain model. A
      fictitious noise of small intensity is also added to the measurement equation
      and, following linearization of the process equation, a Kalman filter is applied
      to reconstruct the shear modulus profile. We present several numerical
      experiments, some of which also bring forth the relative advantages of the
      proposed approach over a deterministic reconstruction based on a quasi-Newton
      search.

PMID- 19088394
TI  - Unusual case of left ventricular pseudoaneurysm.
AB  - A 71 year-old man with a history of previous anterior myocardial infarction,
      triple coronary artery bypass graft and left ventricular (LV) aneurysmectomy was
      admitted to the cardiology unit for chest pain. Physical examination showed a
      pulsing mass in the left chest wall. Cardiac multislice computed tomography
      showed a rare case of LV pseudoaneurysm (6.3 x 6 x 10 cm) communicating by a
      fistulous trait (1 cm) with the left anterior chest wall (C7-C8), creating a
      subfascial mass (7.1 x 3.6 cm).

PMID- 19088395
TI  - Successful treatment of cardiogenic shock caused by humoral cardiac allograft
      rejection.
AB  - The progress of immunosuppressive therapy has made heart transplantation the
      standard therapy for end-stage heart failure. However, humoral rejection of the
      cardiac allograft is still a challenging problem associated with high incidence
      of graft loss and patient mortality. The present patient developed profound
      cardiogenic shock requiring extracorporeal life support on the 8th day after
      heart transplantation. Endomyocardial biopsy revealed no cellular rejection, and
      complement component C4d was positively stained on the capillary endothelium. The
      patient was successfully treated with repeated plasmapheresis and administration
      of anti-CD20 monoclonal antibody, rituximab, as well as with steroid pulse and
      increased standard immunosuppressive medication.

PMID- 19088396
TI  - Marked aortic valve stenosis progression after receiving long-term aggressive
      cholesterol-lowering therapy using low-density lipoprotein apheresis in a patient
      with familial hypercholesterolemia.
AB  - In 1982, a 49-year-old Japanese woman had been referred to our hospital for
      further investigation of her hypercholesterolemia. She was diagnosed as
      heterozygous familial hypercholesterolemia, because of Achilles tendon xanthoma
      and a family history of primary hypercholesterolemia. Three years later, she had
      chest pain on effort and angina pectoris was diagnosed by coronary angiography.
      At that time, she underwent coronary artery bypass grafting surgery with 2
      saphenous vein grafts (SVG). Because more aggressive cholesterol-lowering therapy
      was needed for secondary prevention of coronary artery disease (CAD), weekly low
      density lipoprotein (LDL) apheresis was started postoperatively, combined with
      drug therapy. Since 1986, her serum total cholesterol levels before and after LDL
      apheresis remained approximately 200 mg/dl and 90 mg/dl, respectively. Although
      her coronary sclerosis, including the SVG, did not progress appreciably for a
      period of 20 years, stenotic changes of the aortic valve developed rapidly at age
      70, leading to aortic valve replacement surgery in 2005 at age 72. These findings
      suggest that careful attention to the progression of aortic valve stenosis is
      needed for extreme hypercholesterolemic patients even under optimal cholesterol
      lowering therapy for the secondary prevention of CAD.

PMID- 19088397
TI  - Successful combined treatment of primary cardiac malignant lymphoma with urgent
      cardiac operation and chemotherapy.
AB  - A 56-year-old man, suffering from rapidly worsening general fatigue, dyspnea on
      exercise and epigastralgia, was referred for evaluation and treatment of a
      cardiac tumor. Transthoracic echocardiography showed a 6-cm large mass occupying
      both the right ventricle and atrium. Gallium scintigraphy showed high uptake in
      the tumor site. Lymphoma was highly suggested. Urgent operation was performed and
      as much tumor and thrombus were removed as possible. The postoperative course was
      good, with cessation of right heart failure. Pathological examination suggested
      malignant lymphoma, diffuse large B-cell type. The patient was treated with
      rituximab, cyclophosphamide, Adriamycin, vincristine, and prednisone (CHOP-R)
      postoperatively and has survived for 2 years without signs of recurrence.

PMID- 19088398
TI  - Mature adipocyte-derived dedifferentiated fat cells can trans-differentiate into
      osteoblasts in vitro and in vivo only by all-trans retinoic acid.
AB  - We investigated whether de-differentiated fat (DFAT) cells, a mature adipocyte
      derived preadipocyte cell line, can be induced to trans-differentiate into
      osteoblasts in vitro and in vivo. All-trans retinoic acid (RA) induced expression
      of osteoblast-specific mRNAs encoding Cbfa1/Runx2, osterix, alkaline phosphatase,
      osteopontin, parathyroid hormone receptor, and osteocalcin in the DFAT cells, but
      did not induce the expression of adipocyte-specific mRNAs encoding PPARgamma2,
      C/EBPalpha, and GLUT4. Moreover, alkaline phosphatase activity was expressed in
      DFAT cells and the cells underwent mineralization of the bone matrix in vitro.
      Furthermore, when DFAT cells were transplanted subcutaneously into C57BL/6N mice
      in diffusion chambers, these cells formed ectopic osteoid tissue without any host
      cell-invasion of the chambers. These results indicate that DFAT cells derived
      from mature adipocytes can be converted into fully differentiated osteoblasts in
      vitro and in vivo using RA. DFAT cells provide a unique model for studying the
      lineage commitment of the adipocytes and osteoblasts derived from mesenchymal
      stem cells. Identification of the pathways that regulate these processes could
      lead to the development of new therapeutic strategies for control of unwarranted
      growth of bone and adipose tissue.

PMID- 19088399
TI  - Urinary iodine concentrations in urban and rural areas around Chernobyl Nuclear
      Power Plant.
AB  - In 2007, we screened urinary iodine (UI) concentrations in urban (Gomel city) and
      in rural areas (Hoiniki city) of the Gomel Region, Republic of Belarus, which was
      heavily contaminated by the accident at the Chernobyl Nuclear Power Plant, in
      order to evaluate the current state of iodine supplementation in these areas.
      Median levels of UI were 220.5 microg/L (151.5-358.5) microg/L in Gomel city, and
      228.0 microg/L (130.0-337.5) microg/L in Hoiniki city. Urinary concentrations in
      Gomel city were significantly improved, as compared to our previous results in
      2000 (p<0.001). There were no differences of UI concentrations between Gomel city
      and Hoiniki city (p = 0.39), and none of the samples showed moderate (<50
      microg/L) or severe (<20 microg/L) iodine deficiency in either city. These
      results suggest that the state of iodine supplementation has improved in rural
      areas, as well as in urban areas in the Republic of Belarus, probably due to
      appropriate fortification of iodized salt in this region.

PMID- 19088400
TI  - Hormonal alterations in prepubertal children with iron deficiency.

PMID- 19088401
TI  - Successful treatment of anaplastic thyroid carcinoma with a combination of oral
      valproic acid, chemotherapy, radiation and surgery.
AB  - Anaplastic thyroid carcinoma (ATC) is the most aggressive of thyroid cancers
      whose treatment is not yet established and mortality is extremely high. Recent in
      vitro studies have shown that valproic acid (VA), a newly identified histone
      deacetilase (HDAC) inhibitor, induces apoptosis, modulates differentiation gene
      expression of thyroid tumors and enhances the sensitivity of anaplastic cancer
      cell lines to doxorubicin. We report a case of successful treatment of anaplastic
      thyroid carcinoma with a combination of oral valproic acid, chemotherapy
      consisting of cisplatin and doxorubicin, external and intra-operative radiation
      and surgery. Tumor volume decreased by 50.7% under CT measurement and 44.6% under
      sonogram measurement over the course of the treatment. No significant rebound of
      tumor size was observed between each cycle of chemotherapy. Serial cytology
      performed via fine needle aspiration (FNA) presented a rapidly changing profile
      of cell types, starting with anaplastic and proceeding through increasingly well
      differentiated presentations. Only microscopic remnants of ATC cells were found
      in the histological examination of the resected thyroid. Ga scintigraphy and
      whole body PET scan six months after surgery revealed no evidence of recurrence
      or metastasis. As of Nov. 22, 2008, the patient is alive and disease free two
      years after diagnosis.

PMID- 19088403
TI  - Bibliometric research in occupational health.

PMID- 19088402
TI  - A novel mouse model for type 2 diabetes and non-alcoholic fatty liver disease:
      spontaneous amelioration of diabetes by augmented beta cell mass.
AB  - Given the potential for beta-cells to increase their mass, glucose intolerance
      might be ameliorated by a compensatory increase in beta-cell mass. However, it
      remains uncertain whether such amelioration is feasible in vivo. In this study,
      we investigated glucose tolerance, islet morphology, and islet gene expression of
      Fatty Liver Shionogi (FLS) mice, a model for non-alcoholic fatty liver disease
      (NAFLD). Relative to control mice, FLS mice showed an age-dependent increase in
      glucose intolerance up to the age of 24 weeks, leading to the development of
      diabetes. After this time, glucose tolerance ameliorated spontaneously and
      diabetes resolved by 48 week of age, associated with marked hyperinsulinemia.
      Islets of the FLS mice demonstrated a marked increase in beta-cell mass with an
      increase in beta-cell numbers. Islet gene expression analysis in FLS mice
      demonstrated no changes in gene expression of glucokinase or insulin receptor
      substrate 2. These data demonstrated that the 24-week-old FLS mouse is a model
      for type 2 diabetes with NAFLD and that the 48-week-old FLS mouse exhibits
      spontaneous amelioration of type 2 diabetes associated with augmented beta-cell
      number/mass.

PMID- 19088404
TI  - A review of work schedule issues and musculoskeletal disorders with an emphasis
      on the healthcare sector.
AB  - Musculoskeletal disorders (MSDs) are a significant cause of morbidity in
      healthcare workers. The influence of shift work and long work hours on risk for
      MSDs is an area that needs further exploration. The purpose of this report is to
      assess research progress and gaps across studies that examined the relationship
      between demanding work schedules and MSD outcomes. A literature search identified
      23 peer-reviewed publications in the English language that examined MSDs and long
      work hours, shift work, extended work shifts, mandatory overtime, or weekend
      work. Eight studies that examined long work hours and had some controls for
      physical job demands reported a significant increase in one or more measures of
      MSDs. Fourteen studies examining shift work had incomparable methods and types of
      shift work, and therefore, no clear trends in findings were identified. A small
      number of studies examined mandatory overtime, work on weekends and days off, and
      less than 10 h off between shifts. Given the complexity of the work schedule
      research topic, relatively few studies have adequately examined the relationship
      of work schedules and musculoskeletal outcomes. The review discusses research
      gaps including methodological issues and suggests research priorities.

PMID- 19088405
TI  - Asbestos-related occupational lung diseases in NSW, Australia and potential
      exposure of the general population.
AB  - Asbestos is a fibrous silicate which is recognized as causing a variety of lung
      disorders including malignant mesothelioma of the pleura, lung cancer and
      asbestosis. Asbestos use has been banned in most developed countries but exposure
      still occurs under strict regulation in occupational settings and also
      occasionally in domestic settings. Although the hazards of asbestos are well
      known in developed countries, awareness of its adverse health effects is less in
      other parts of the world, particularly when exposure occurs in non-occupational
      settings. Experience of asbestos use and its adverse heath effects in developed
      countries such as Australia have resulted in development of expertise in the
      diagnosis and treatment of asbestos-related diseases as well as in screening and
      this can be used to help developing countries facing the issue of asbestos
      exposure.

PMID- 19088406
TI  - Suicide mortality of young, middle-aged and elderly males and females in Japan
      for the years 1953-96: time series analysis for the effects of unemployment,
      female labour force, young and aged population, primary industry and population
      density.
AB  - Effects of nine social life indicators on age-adjusted and age-specific annual
      suicide mortality of male and female Japanese population in the years 1953-96
      were investigated by multiple regression analysis on time series data.
      Unemployment rate was significantly related to the age-adjusted mortality in both
      males and females. Also, female labour force participation was positively related
      to the male mortality; persons and 65 and above was inversely related to the male
      mortality. Results on the age-specific mortality indicated that: during the 44
      yr, (1) unemployment significantly related with the mortality of young, middle
      aged and elderly males and young females; (2) female labour force participation
      significantly related with the mortality of young and elderly males and young
      females; aged population significantly related with the mortality of middle-aged
      and elderly males; (4) young population significantly related with the mortality
      of young and middle-aged males and females; (5) divorce significantly related
      with the mortality of middle-aged and elderly males and young males and females;
      (6) persons employed in primary industries significantly related with the
      mortality in middle-aged males and young males and females; and (7) population
      density significantly related with the mortality of middle-aged males and young
      females.

PMID- 19088407
TI  - Energy absorption of seated occupants exposed to horizontal vibration and role of
      back support condition.
AB  - Absorbed power characteristics of seated human subjects under fore-aft (x-axis)
      and lateral (y-axis) vibration are investigated through measurements of dynamic
      interactions at the two driving-points formed by the body and the seat pan, and
      upper body and the backrest. The experiments involved: (i) three back support
      conditions (no back support, and back supported against a vertical and an
      inclined backrest); (ii) three seat pan heights (425, 390 and 350 mm); and three
      magnitudes (0.25, 0.5 and 1.0 m/s2 rms acceleration) of band limited random
      excitations in 0.5-10 Hz frequency range, applied independently along the x- and
      y- axes. The force responses, measured at the seat pan and the backrest are
      applied to characterize total energy transfer reflected on the seat pan and the
      backrest. The mean responses suggest strong contributions due to back support,
      and direction and magnitude of vibration. In the absence of a back support, the
      seat pan responses dominated in lower frequency bands centered at 0.63 and 1.25
      Hz under both directions of motion. Most significant interactions of the upper
      body against the back support was observed under fore-aft vibration. The addition
      of back support caused the seat pan response to converge to a single primary peak
      near a higher frequency of 4 Hz under x- axis, with only little effect on the y
      axis responses. The back support serves as an additional source of vibration to
      the occupant and an important constraint to limit the fore-aft movement of the
      upper body and thus relatively higher energy transfer under. The mean responses
      were further explored to examine the Wd frequency-weighting used for assessing
      exposure to horizontal vibration. The results show that the current weighting is
      suited for assessing the vibration exposure of human subjects seated only without
      a back support.

PMID- 19088408
TI  - L-arginine reduces mercury accumulation in thymus of mercury-exposed mice: role
      of nitric oxide synthase activity and metallothioneins.
AB  - Mercury, an occupational and environmental contaminant, is a well-recognized
      health hazard. The thymus is a target for inorganic mercury (Hg2+); thymic
      function is impaired in Hg2+ intoxication and is partially restored by
      simultaneous L-arginine supplementation. The nitric oxide (NO)-nitric oxide
      synthase (NOS) pathway and metallothioneins (MTs) were studied to investigate the
      role of L-arginine in thymic function restoration after mercury exposure. Mice
      received a higher and a lower dose of inorganic mercury, with and without L
      arginine supplementation. Saline-treated mice were used as controls. Thymus
      weight and thymulin were measured as indices of thymic function. Mice treated
      with Hg2+ alone displayed an accumulation of metal in the thymus, reduced NOS
      activity, a lower plasma nitrite plus nitrate concentration and an increased MTs
      expression compared with control mice. L-arginine supplementation was associated
      with lower Hg2+ concentrations in the organ and partial preservation of other
      measures. Reduced accumulation of Hg2+ in mice dosed with L-arginine was probably
      related to greater NO production and NO-MTs interactions.

PMID- 19088409
TI  - A study for safety and health management problem of semiconductor industry in
      Taiwan.
AB  - The main purpose of this study is to discuss and explore the safety and health
      management in semiconductor industry. The researcher practically investigates and
      interviews the input, process and output of the safety and health management of
      semiconductor industry by using the questionnaires and the interview method which
      is developed according to the framework of the OHSAS 18001. The result shows that
      there are six important factors for the safety and health management in Taiwan
      semiconductor industry. 1. The company should make employee clearly understand
      the safety and health laws and standards. 2. The company should make the safety
      and health management policy known to the public. 3. The company should put
      emphasis on the pursuance of the safety and health management laws. 4. The
      company should prevent the accidents. 5. The safety and health message should be
      communicated sufficiently. 6. The company should consider safety and health norm
      completely.

PMID- 19088410
TI  - A simple direct injection method for GC/MS analysis of PAHs in particulate
      matter.
AB  - A simple direct injection method for analysis of polycyclic aromatic hydrocarbons
      (PAHs) or other organic components of particulate matter by gas
      chromatography/mass spectrometry (GC/MS) was developed. This method uses a small
      custom brass capsule to insert a particulate sample deposited on a quartz fiber
      filter or powdery sample directly into a GC injector inlet. This approach was
      applied in the analysis of PAHs in diesel emissions and other particulate
      samples, which are introduced into the GC and analyzed by MS using selected ion
      monitoring mode. Quantitation is based on the concentration of PAHs in a standard
      reference material (SRM), which are certified by US National Institute of
      Standard Technology to avoid matrix effects on extraction efficiency. A standard
      filter is prepared by deposition of small amount of SRM of diesel particulate or
      ambient PM on quartz fiber filter. By this method, the linearity for 12 kinds of
      PAHs (3 to 6 rings) was demonstrated from 0.022 mg to 0.65 mg of SRM 1650. The
      linearity of BaP, for example, was confirmed from 0.028 to 0.845 ng. The
      reproducibility of this method determined by analyzing the standard filter was
      15.4%. By selecting an appropriate SRM as a standard material, this method is
      applicable for analyzing PAHs in fine particulate matter of less than 1 microm
      from various origins. Preliminary results for a series of ambient particulate
      matter, roadside PM, diesel soot and sidestream smoke, are presented. This method
      enables analysis of organic chemical substances, for example PAHs, in PM without
      any pretreatment using organic solvent, and without any expensive modification of
      GC instrument.

PMID- 19088411
TI  - Sleeping and working hours of residents at a national university hospital in
      Japan.
AB  - This study aimed to examine the status of time spent working and sleeping by
      resident doctors before the introduction of the New Training System for Residents
      in Japan. A time-budget survey was conducted over a 4-wk period on 102 residents
      at the Shiga University of Medical Science Hospital, and the response rate among
      residents was 76% of a total of 2,722 person-days. The average number of hours
      spent sleeping was the lowest and spent in the hospital including commuting time
      was the highest in residents of the surgery department, at 4.4 h and 18.9 h,
      respectively. Forty percent of residents reported dozing off at work, with the
      incidence rate being highest in residents of the surgery department (0.7
      times/person-day). Dozing appeared to occur in response to the lack of sleep and
      fatigue, since the same residents slept longer on nights before days they
      reported not dozing off than on nights before days when they did doze off. Strong
      correlations were observed between the number of sleeping and working hours and
      between working hours and the number of patients in a resident's care. In order
      to maintain high standards of training and to get sufficient sleep it is
      therefore necessary for residents to manage their work and the number of patients
      in their care.

PMID- 19088412
TI  - Validation of the Dutch Occupational Impact of Sleep Questionnaire (OISQ).
AB  - Sleep problems are often under-diagnosed, but may have a profound impact on work
      performance. The purpose of this study was to validate the Dutch version of the
      Occupational Impact of Sleep Questionnaire (OISQ). A total of 555 adults with a
      regular daytime job completed the OISQ. In addition, they also completed the
      Pittsburgh Sleep Quality Index (PSQI), Epworth Sleepiness Scale (ESS) and the
      SLEEP-50 questionnaire. 443 surveys were included in the analysis (220 men and
      223 women). The Dutch OISQ had high reliability (Chronbach's alpha=0.96). OISQ
      scores correlated significantly with scores on the SLEEP-50 questionnaire, ESS,
      and PSQI (p<0.0001). Mean score on the OISQ was 14.0. Poor sleepers (OISQ score
      around 20) had approximately double the OISQ score as good sleepers (OISQ score
      around 10), irrespective of this classification was based on self-ratings, PSQI
      scores or SLEEP-50 scores. The Dutch OISQ is a suitable tool to examine the
      occupational impact of sleep.

PMID- 19088413
TI  - Associations between cardiovascular risk factors and carotid atherosclerosis in
      middle-aged Japanese men with multiple risk factors.
AB  - To examine the relationship between cardiovascular risk factors and prevalence of
      carotid atherosclerosis in Japanese middle-aged men with multiple risk factors,
      110 Japanese men aged 36 to 60 yr were recruited based on the presence of all of
      the following factors detected during a screening survey: 1) body mass index
      (BMI) > or = 25 kg/m2; 2) systolic blood pressure (SBP) > or = 140 mmHg and/or
      diastolic blood pressure > or = 90 mmHg; 3) serum levels of triglycerides (TG) >
      or = 150 mg/dl and/or total cholesterol (T-ChoL) levels > or = 220 mg/dl and/or
      high density lipoprotein cholesterol (HDL-C) levels < 40 mg/dl; and 4) fasting
      serum glucose > or = 110 mg/dl and/or hemoglobin A1C > or = 5.6%. After
      adjustment for age and cardiovascular risk factors, the odds ratio (95%
      confidence interval) of carotid atherosclerosis associated with a 1-SD increment
      in HDL-C was 0.4 (95%CI: 0.2 to 0.9). We also detected a borderline association
      for anti-hypertension medication use, an indicator for advanced hypertension,
      with an odds ratio of 2.7 (95%CI: 1.0 to 7.4) after multivariable adjustment. The
      other risk factors, i.e. BMI, SBP, T-ChoL, TG, diabetes, smoking and drinking
      status did not show significant associations with carotid atherosclerosis. In
      conclusion, low HDL-C and advanced hypertension were significant correlates of
      carotid atherosclerosis for middle-aged Japanese men with multiple risk factors.

PMID- 19088414
TI  - Effects of perceived job insecurity on perceived anxiety and depression in
      nurses.
AB  - Dramatic changes in workplace structure and environment have increased the
      importance of psychosocial factors and job insecurity in working life. Job
      insecurity is shown to have a negative impact on mental and physical health.
      Health care transformation in Turkey increases the threat of job insecurity for
      many workers in the health care sector. Therefore the aim of this cross-sectional
      study was to determine the effects of perceived job insecurity on perceived
      depression and anxiety in nurses working in the private health sector in Izmir,
      Turkey. There were 16 private hospitals in Izmir of which 11 accepted to
      participate. Perceived quantitative (5 items) and qualitative (4 items) job
      insecurity were measured by means of structured questionnaires. The hospital
      anxiety and depression scale was used to evaluate subjective anxiety and
      depression. Job strain was assessed by the Demand-Control-Support Questionnaire.
      Chi2 and logistic regression tests were used for analysis. A total number of 462
      nurses were surveyed. Perceived anxiety (OR: 2.2, 95% CI: 1.2-3.9) and depression
      (OR: 2.5, 95% CI: 1.6-4.1) were significantly associated with qualitative job
      insecurity. Similarly quantitative job insecurity was associated with perceived
      anxiety (OR: 3.4, 95% CI: 1.9-6.2) and depression (OR: 2.2, 95% CI: 1.4-5.6) in
      nurses. It has been concluded that qualitative and quantitative job insecurity
      significantly affected perceived anxiety and depression levels in nurses working
      in private hospitals. Prevention oriented research is needed for policy
      development.

PMID- 19088415
TI  - Alleviation of heat strain by cooling different body areas during red pepper
      harvest work at WBGT 33 degrees C.
AB  - The purpose of the present study was to examine the effects of different types of
      personal cooling equipments (PCE) on the alleviation of heat strain during red
      pepper harvest simulated in a climatic chamber. The experiment consisted of eight
      conditions: 1) Control, 2) Neck cooling scarf A with a cooling area of 68 cm2, 3)
      Neck cooling scarf B (cooling area 154 cm2), 4) Brimmed hat with a frozen gel
      pack, 5) Cooling vest (cooling area 606 cm2), 6) Hat+Neck Scarf B, 7) Hat+Vest,
      and 8) Hat+Neck Scarf B+Vest. Twelve subjects worked a red pepper harvest
      simulated in a climatic chamber of WBGT 33 degrees C. The result showed that
      rectal temperature (T(re)) was effectively maintained under 38 degrees C by
      wearing PCE. Mean skin temperature (T(sk)) and heart rate (HR) became more stable
      through wearing PCE. When wearing the 'Hat+Scarf B+Vest', particularly, T(sk) and
      HR quickly decreased to the comfort level during the mid-rest stage. We confirmed
      that the vest with a cooling area of only 3.3% body surface area (BSA) was
      effective in alleviating heat strain in a simulated harvest work. Furthermore,
      the heat strain of farm workers can be considerably eliminated by the combination
      of the cooling vest, a scarf, and a brimmed hat, with the total cooling area of
      4.2% BSA.

PMID- 19088416
TI  - Establishment of one-axis vibration test system for measurement of biodynamic
      response of human hand-arm system.
AB  - Prolonged exposure to hand-arm vibration (HAV) due to use of hand-held power
      tools leads to an increased occurrence of symptoms of disorders in the vascular,
      neurological, and osteo-articular systems of the upper limbs called hand-arm
      vibration syndrome (HAVS). Biodynamic responses of the hand-arm system to
      vibration can be suggestive parameters that give us better assessment of exposure
      to HAV and fundamental data for design of low-vibration-exposure power tools.
      Recently, a single axis hand-arm vibration system has been installed in the Japan
      National Institute of Occupational Safety and Health (NIOSH). The aims of this
      study were to obtain the fundamental dynamic characteristics of an instrumented
      handle and to validate the performance and measurement accuracy of the system
      applied to dynamic response measurement. A pseudo-random vibration signal with a
      frequency range of 5-1,250 Hz and a power spectrum density of 1.0 (m/s2)2/Hz was
      used in this study. First the dynamic response of the instrumented handle without
      any weight was measured. After this measurement, the dynamic response measurement
      of the handle with weights mounted on the handle was performed. The apparent mass
      of a weight itself was obtained by using the mass cancellation method. The mass
      of the measuring cap on the instrumented handle was well compensated by using the
      mass cancellation method. Based on the 10% error tolerance, this handle can
      reliably measure the dynamic response represented by an apparent mass with a
      minimum weight of 2.0 g in a frequency range of 10.0 to 1,000 Hz. A marked
      increase in the AM magnitude of the weights of 15 g and 20 g in frequency ranges
      greater than 800 Hz is attributed not to the fundamental resonance frequency of
      the handle with weights, but to the fixation of the weight to the measuring cap.
      In this aspect, the peak of the AM magnitude can be reduced and hence should not
      be an obstacle to the biodynamic response measurement of the human hand-arm
      system. On the basis of the results obtained in this study, we conclude that this
      hand-arm vibration test system can be used to measure biodynamic response
      parameters of the human hand-arm system.

PMID- 19088417
TI  - Myoclonic encephalopathy after exposure to trichloroethylene.
AB  - Trichloroethylene is a widely-used industrial solvent that is absorbed through
      the digestive or respiratory tracts or cutaneously. It has a selective tropism
      for the cardiovascular and central nervous systems and may cause death due to
      cardiac arrest or neurological sequelae. We present the case of a 25-yr-old women
      who was exposed to trichloroethylene in the workplace for 18 months and who
      developed a disabling myoclonic encephalopathy. Non-toxicological causes were
      excluded. Although the exposure ceased, the disease progressed with thalamic and
      cerebellar involvement. The patient, who had only a partial response to
      symptomatic treatment, suffered severe limitations in the activities of daily
      living and was registered as permanently disabled due to a work-related
      disability.

PMID- 19088418
TI  - Eryptosis, a window to systemic disease.
AB  - Similar to apoptosis of nucleated cells, suicidal erythrocyte death or eryptosis
      is characterized by cell shrinkage, membrane blebbing and membrane phospholipid
      scrambling with phosphatidylserine exposure at the cell surface. Signaling of
      eryptosis involves formation of prostaglandin E(2) with subsequent activation of
      cation channels and Ca(2+)-entry and/or release of platelet activating factor
      (PAF) with subsequent activation of sphingomyelinase and formation of ceramide.
      Ca(2+) and ceramide stimulate cell membrane scrambling. Ca(2+) further activates
      Ca(2+)-sensitive K(+)-channels leading to cellular KCl loss and cell shrinkage
      and stimulates the protease calpain resulting in degradation of the cytoskeleton.
      Injuries triggering eryptosis may similarly compromise survival of nucleated
      cells. The case is made that analysis of enhanced eryptosis may direct to the
      pathophysiology of systemic disease. Examples presented include drug side
      effects, sepsis, haemolytic uremic syndrome, Wilson's disease, phosphate
      depletion and a rare condition caused by a mutation in GLUT1 turning the carrier
      into a cation channel.

PMID- 19088419
TI  - Lipopeptides in the triggering of erythrocyte cell membrane scrambling.
AB  - Sepsis is paralleled by anemia, an effect partially resulting from eryptosis, the
      suicidal death of erythrocytes. Eryptosis is characterized by cell membrane
      scrambling with phosphatidylserine exposure at the erythrocyte surface. Pathogen
      induced eryptosis may partially result from interaction of bacterial cell wall
      components such as lipoproteins with the erythrocyte cell membrane. The present
      study explored, whether the synthetic lipopeptide Pam3CSK4 mimicking the acylated
      amino terminus of bacterial lipoproteins triggers eryptosis. According to annexin
      V-binding in FACS analysis, Pam3CSK4 (1 microg/ml) stimulated phosphatidylserine
      exposure, an effect significantly blunted in the nominal absence of Ca(2+).
      According to Fluo3 fluorescence, Pam3CSK4 increased cytosolic Ca(2+) activity and
      moderately stimulated erythrocytic ceramide formation, both major triggers of
      eryptosis. In conclusion, bacterial lipoproteins participate in the stimulation
      of erythrocyte cell membrane scrambling by bacterial cell wall components. Thus,
      lipoprotein-dependent suicidal erythrocyte death may contribute to the pleotropic
      effects of sepsis.

PMID- 19088420
TI  - Suicidal death of erythrocytes due to selenium-compounds.
AB  - Selenium is an essential element incorporated into selenoproteins. Selenium
      deficiency may predispose to immune deficiency, mood disorders, and cancer. On
      the other hand, excessive environmental exposure to selenite may cause a variety
      of disorders including anemia. At least in theory, the anemia could result from
      accelerated suicidal erythrocyte death or eryptosis, characterized by cell
      shrinkage and phosphatidylserine exposure at the erythrocyte surface. Eryptosis
      is triggered by an increase in the cytosolic Ca(2+) concentration and by
      ceramide. The present experiments explored, whether high concentrations of
      selenite stimulate eryptosis. According to Fluo3 fluorescence, selenite (>or=200
      microg/l sodium selenite) within 48 hours significantly increased the cytosolic
      Ca(2+) concentration in human erythrocytes. According to binding of selective
      fluorescent antibodies, selenite (>or= 200 microg/l) significantly increased
      ceramide formation. Annexin V-binding demonstrated that selenite (>or=200
      microg/l) significantly increased phosphatidylserine exposure of erythrocytes.
      Forward scatter analysis further revealed that selenite (>or=200 microg/l)
      significantly decreased cell volume. In contrast to selenite, selenate failed to
      trigger eryptosis. In conclusion, selenite triggers suicidal erythrocyte death at
      least partially by increasing the cytosolic Ca(2+) concentration and by
      stimulating the formation of ceramide. The present study discloses novel cellular
      effects of this essential nutrient.

PMID- 19088421
TI  - A high specificity and affinity interaction with serum albumin stimulates an
      anion conductance in malaria-infected erythrocytes.
AB  - The intraerythrocytic development of P. falciparum induces New Permeability
      Pathways (NPP) in the membrane of the parasitized erythrocyte which provide the
      parasite with nutrients, adjust the erythrocyte electrolyte composition to the
      needs of the parasite, and dispose of metabolic waste products and osmolytes.
      Patch-clamp recordings identified inwardly and outwardly rectifying (OR) anion
      conductances in the host erythrocyte membrane as electrophysiological correlate
      of the NPP. The OR conductance is regulated by serum. Here we show that serum
      albumin (SA) stimulated OR-generated Cl(-) and lactate outward currents with an
      EC(50) of approximately 100 nM while other proteins such as ovalbumin or casein
      did not. The stimulatory efficacy did not differ between fatty acid free bovine
      SA and recombinant human SA and disruption of the SA tertiary structure abolished
      the effect suggesting that intact SA protein and not other bound factors interact
      with the erythrocyte membrane. Taken together, the data indicate a high affinity
      and specificity interaction of native SA with the parasitized erythrocytes which
      might underlie the observed dependence of P. falciparum growth in vitro on SA.

PMID- 19088422
TI  - Influence of amitriptyline on eryptosis, parasitemia and survival of Plasmodium
      berghei-infected mice.
AB  - Plasmodia express a sphingomyelinase, which is apparently required for their
      development. On the other hand, the sphingomyelinase product ceramide has
      previously been shown to delay parasite development. Moreover, ceramide triggers
      suicidal erythrocyte death or eryptosis, characterized by exposure of
      phosphatidylserine at the erythrocyte surface and cell shrinkage. Accelerated
      eryptosis of infected erythrocytes is considered to clear infected erythrocytes
      from circulating blood and, thus, to favourably influence the clinical course of
      malaria. The present experiments explored whether the sphingomyelinase inhibitor
      amitriptyline or genetic knockout of host acid sphingomyelinase influence in
      vitro parasite growth, eryptosis of Plasmodium falciparum-infected human
      erythrocytes, in vivo parasitemia and survival of P. berghei-infected mice.
      Phosphatidylserine exposure was determined by annexin V-binding and cell volume
      by forward scatter in FACS analysis. In vitro infection of human erythrocytes
      increased annexin- binding, an effect blunted in the presence of amitriptyline
      (>or=50 microM). Amitriptyline did not significantly alter intraerythrocytic
      parasite development but significantly (>or= 1 microM) delayed the increase in
      parasitemia in vitro. Most importantly, amitriptyline treatment (1 mM in drinking
      water) resulted in a significant delay of parasitemia and death of infected mice.
      However, upon infection, ceramide formation was stimulated in both, acid
      sphingomyelinase knockout mice (Smpd1(-/-)) and their wild type littermates
      (Smpd1(+/+)). Parasitemia following P. berghei infection was significantly lower
      in Smpd1(-/-) than in Smpd1(+/+) mice but did not significantly extend the life
      span of infected animals. In conclusion, mammalian and parasite sphingomyelinase
      contribute to ceramide formation during malaria, whereby the parasite
      sphingomyelinase ultimately determines the course of the infection. Amitriptyline
      presumably blocks both sphingomyelinases and, thus, its use might be a novel
      strategy to treat malaria.

PMID- 19088423
TI  - Extracellular calcium-sensing receptor mediated signalling is involved in human
      vascular smooth muscle cell proliferation and apoptosis.
AB  - Calcium-sensing receptor (CaSR) plays key role in vascular calcification in
      patients with chronic kidney disease (CKD). We investigated the role of CaSR in
      regulating smooth muscle cell (SMC) proliferation and apoptosis. Incubation with
      300 microM neomycin (CaSR agonist) resulted in 7.5-fold (p<0.05) increase in
      ERK1,2 phosphorylation. It was reduced (p<0.01) by 10 microM PD98059 (MEK1
      inhibitor), indicating that CaSR agonist-induced effects were mediated via
      MEK1/ERK1,2 pathway. ERK1,2 phosphorylation was abolished by 5 microM U73122 (PLC
      inhibitor), indicating that PLC signalling was crucial for MEK1/ERK1,2
      activation. Confirming PLC activation, inositol triphosphate (IP3) production was
      increased by neomycin/gentamycin (p<0.05) and reduced by U73122. To confirm that
      ERK1,2 and PLC signalling were mediated via CaSR, Human Aortic SMC (HAoSMC) were
      transfected with CaSR siRNA. CaSR knockdown resulted in lower ERK1,2 neomycin
      response and IP3 production (p<0.01). Neomycin increased HAoSMC proliferation >3
      fold, which was reduced in CaSR knockdown cells (p<0.01) and further inhibited by
      PD98059 and U73122 (p<0.05). Apoptosis was not affected by neomycin treatment.
      U73122 produced 3.5-fold increase in HAoSMC apoptosis, which was further
      increased by CaSR knockdown (5-fold, p<0.05). In conclusion, stimulation of CaSR
      leads to activation of MEK1/ERK1,2 and PLC pathways and up-regulation of cell
      proliferation. CaSR-mediated PLC activation is important for SMC survival and
      protection against apoptosis.

PMID- 19088424
TI  - Acute effects of haemodialysis on pro-/anti- apoptotic genes in peripheral blood
      leukocytes.
AB  - Several studies have implicated a remarkable dysfunctional apoptotic state and/or
      response in ESRD patients. Previously published studies are controversial with
      respect to acute effects of haemodialysis (HD) treatment on up- or downregulation
      of apoptotic genes. Twenty-eight chronic HD patients were haemodialysed for 4
      hours with a 4008 dialyser using high-flux membranes. For subgroup analysis,
      patients were separated into a low (up to 0.5 mg/dl) and a high (0.5 to 5.0
      mg/dl) CRP group. Blood was drawn prior to HD and 240 min after initiation of HD.
      Acute changes of transcript levels encoding pro- or anti-apoptotic genes were
      analyzed in RNA immediately isolated from blood leukocytes using quantitative
      real-time PCR. In the present study, we detected a significant elevation of the
      death receptor CD95/Fas (induction factor (IF) 1.55 +/- 0.16), the death receptor
      5 (DR5) (IF 1.17 +/- 0.08), and caspase 8 (IF 1.37 +/- 0.14) gene expression
      during HD. mRNA levels of the respective ligands (CD95L, TRAIL), of the caspase 5
      and anti-apoptotic Bcl-2 family members such as Bcl-2 and Bcl2l2 were slightly,
      but not significantly, increased after HD treatment. An additional anti-apoptotic
      molecule, BAG3, was found to be slightly, but significantly, induced after HD (IF
      1.16 +/- 0.07). In addition to being an activator of immune cells, CD40L has been
      shown to be strongly induced after HD treatment (IF 1.70 +/- 0.20). Subgroup
      analysis revealed no significant differences between low vs. high CRP patient
      groups or diabetic vs. non-diabetic patients. These results indicate a marked
      influence of routine haemodialysis treatment on the transcription of pro- and
      anti-apoptotic molecules and the involvement of the extrinsic pathway for
      apoptosis through the activation of death receptors and the initiator caspase 8.
      Furthermore, following dialysis, lymphocytes seem to be activated by CD40L, which
      represents an early T-cell activation marker.

PMID- 19088425
TI  - Cell growth inhibition, G2/M cell cycle arrest, and apoptosis induced by
      chloroquine in human breast cancer cell line Bcap-37.
AB  - Chloroquine is an antimalarial drug that has been used in the treatment and
      prophylaxis of malaria since the 1950s. The present study was undertaken to
      examine the effects of chloroquine on Bcap-37 human breast cancer cells' growth,
      cell cycle modulation, apoptosis induction, and associated molecular alterations
      in vitro. The chloroquine treatment decreased the viability of Bcap-37 cells in a
      concentration- and time-dependent manner, which correlated with G(2)/M phase cell
      cycle arrest. The chloroquine-mediated cell cycle arrest was associated with a
      decrease in protein levels/activity of polo-like kinase 1 (Plk1), phosphorylated
      cell division cycle 25C (Cdc25C), phosphorylated extracellular signal-regulated
      kinase 1/2 (ERK1/2), phosphorylated Akt. The chloroquine-treated Bcap-37 cells
      exhibited a marked decrease in the level of mitochondrial transmembrane potential
      (DeltaPsim), which was accompanied by the activation of caspase-3 and cleaved
      poly(ADP-ribose) polymerase (PARP). Exposure of Bcap-37 cells to chloroquine also
      resulted in the induction of spindle abnormalities. In conclusion, the findings
      in this study suggested that chloroquine might have potential anticancer
      efficacy, which could be attributed, in part, to its proliferation inhibition and
      apoptosis induction of cancer cells through modulation of apoptosis and cell
      cycle-related proteins expressions, down-regulation of mitochondrial
      transmembrane potential (DeltaPsim), and induction of spindle abnormalities.

PMID- 19088427
TI  - S-CMC-Lys protective effects on human respiratory cells during oxidative stress.
AB  - The mucoactive drug S-carbocysteine lysine salt monohydrate (S-CMC-Lys)
      stimulates glutathione (GSH) efflux from respiratory cells. Since GSH is one of
      the most important redox regulatory mechanisms, the aim of this study was to
      evaluate the S-CMC-Lys effects on GSH efflux and intracellular concentration
      during an oxidative stress induced by the hydroxyl radical (xOH). Experiments
      were performed on cultured human respiratory WI-26VA4 cells by means of patch
      clamp experiments in whole-cell configuration and of fluorimetric analyses at
      confocal microscope. xOH exposure induced an irreversible inhibition of the GSH
      and chloride currents that was prevented if the cells were incubated with S-CMC
      Lys. In this instance, the currents were inhibited by the specific blocker
      CFTR(inh)-172. CFT1-C2 cells, which lack a functional CFTR channel, were not
      responsive to S-CMC-Lys, but the stimulatory effect of the drug was restored in
      LCFSN-infected CFT1 cells, functionally corrected to express CFTR. Fluorimetric
      measurements performed on the S-CMC-Lys-incubated cells revealed a significant
      increase of the GSH concentration that was completely hindered after oxidative
      stress and abolished by CFTR(inh)-172. The cellular content of reactive oxygen
      species was significantly lower in the S-CMC-Lys-treated cells either before or
      after xOH exposure. As a conclusion, S-CMC-Lys could exert a protective function
      during oxidative stress, therefore preventing or reducing the ROS-mediated
      inflammatory response.

PMID- 19088426
TI  - Cell death induced by uridine 5'-triphosphate (UTP) in contrast to adenosine 5'
      triphosphate (ATP) in human epidermoid carcinoma cells (A-431).
AB  - OBJECTIVE: Extracellular ATP has been reported as an important signaling molecule
      mediating quite divergent specific biological effects. Recent clinical trials
      suggest a potential role of ATP in cancer treatment. The aim of our study was to
      analyze the mechanisms of UTP in comparison to ATP-mediated cell death in an
      established cell line model (A-431). METHODS: Cell culture and proliferation
      assays, separation of nucleotides by thin-layer technique, measurement of
      cytosolic free Ca(2+), flow cytometry analysis (annexin V), ultra structure, semi
      quantitative RT-PCR, standard statistics. RESULTS: ATP, when added as a single
      dose between 100 and 500 microM to A-431 cell cultures, showed increasing
      cytotoxicity, mainly as apoptosis, with a paradoxically decreasing effect at
      higher concentrations up to 1500 microM. Doses exceeding 1500 microM again led to
      increasing cytotoxicity. UTP at doses between 500 and 3000 microM resulted in
      increasing cell death following a normal sigmoid dose-response model. ATP and UTP
      were degraded by membrane-bound ectoenzymes. ATP degradation products, e.g.
      adenosine, also induced cell death. Dipyridamole, an adenosine uptake inhibitor,
      was able to abolish ATP toxicity, which was also counteracted by the addition of
      uridine. In addition, we found functional and transcriptional evidence for P2
      receptors on A-431 cells. CONCLUSION: Extracellular ATP seems to act via
      degradation to adenosine and consecutive induction of apoptosis. In contrast, we
      were not able to demonstrate analogous mechanisms for cell death mediated by
      extracellular UTP, but were able to provide some evidence of classical ligand
      receptor action of uncleaved UTP on A-431 cells.

PMID- 19088428
TI  - DOCA and TGF-beta induce early growth response gene-1 (Egr-1) expression.
AB  - Renal fibrosis is characterized by excessive accumulation of extracellular matrix
      proteins. Recent findings show that transforming growth factor-beta (TGF-beta)
      induces a rapid but transient expression of early growth response gene-1 (Egr-1)
      by skin fibroblasts. The present study aims to define the role of Egr-1 in
      mineralocorticoid-induced renal fibrosis. Therefore, we transiently transfected
      immortalized human renal fibroblasts (TK188) with recombinant Egr-1 and analysed
      the transcription of several pro-fibrotic genes (Coll1A1, Coll1A2, osteopontin,
      TIMP-1, and CTGF). We also examined Egr-1 expression and the regulation of pro
      fibrotic genes in DOCA- (deoxycorticosterone acetate) and TGF-beta-treated renal
      fibroblasts. Finally, we compared Egr-1 gene expression in DOCA/high salt-induced
      fibrotic kidneys and untreated mice. Egr-1 transfection of TK188 fibroblasts
      induced the expression of TIMP-1 and osteopontin mRNA. Similar results were
      obtained after DOCA-activation of TK188 cells. Stimulation of TK188 with TGF
      beta, but not with DOCA, resulted in elevated Coll1A1/Coll1A2 and CTGF levels. Co
      stimulation with DOCA and TGF-beta was followed by enhanced Egr-1, Coll1A1, TIMP
      1, and CTGF transcription. In conclusion, both DOCA and TGF-beta alone or in
      combination synergistically induced Egr-1 expression by human renal fibroblasts.
      DOCA induction of TIMP-1/osteopontin is Egr-1 dependent, whereas TGF-beta appears
      to induce Coll1A1 and CTGF by an Egr-1 independent pathway. In vivo analyses
      revealed significantly higher Egr-1 transcript levels in DOCA/high salt-induced
      fibrotic kidneys compared to untreated mice. Thus, we show for the first time
      that Egr-1 might participate in DOCA-induced renal fibrosis.

PMID- 19088429
TI  - Troglitazone induced cytosolic acidification via extracellular signal-response
      kinase activation and mitochondrial depolarization: complex I proton pumping
      regulates ammoniagenesis in proximal tubule-like LLC-PK1 cells.
AB  - PURPOSE: To determined the mechanism(s) through which troglitazone induces
      cytosolic acidification and glutamine-dependent ammoniagenesis in pig kidney
      derived LLC-PK1 cells. EXPERIMENTAL DESIGN: Acute experiments measured acid
      extrusion, acid production and simultaneous Extracellular Signal-Regulated Kinase
      activation. TRO-enhanced acid production was correlated with mitochondrial
      membrane potential and rotenone and 5-(N-ethyl-N-isopropyl) amiloride, were
      employed to test specifically the role of Complex I proton pumping. Chronic
      experiments correlated inhibitors of Complex I with prevention of TRO-increased
      ammoniagenesis and affects on glutamine metabolism. RESULTS: Exposure to TRO
      acutely activated Extracellular Signal-Regulated Kinase in a dose dependent
      manner associated with a fall in spontaneous cytosolic pH. Cytosolic acidosis was
      associated with both an increase in acid production and inhibition of
      sodium/hydrogen ion exchanger -mediated acid extrusion. Preventing TRO-induced
      Extracellular Signal-Regulated Kinase activation with Mitogen Activated Protein
      Kinase Kinase inhibitors blocked the increase in acid production, restored
      sodium/hydrogen ion exchanger-activity and prevented cytosolic acidification.
      Mechanistically, increased acid production was associated with a rapid
      mitochondrial depolarization and Complex I proton pumping. Blocking Extracellular
      Signal-Regulated Kinase activation prevented both the fall in Psim and the
      increased acid production suggesting that the former underlies the accelerated
      mitochondrial 'acid production'. Mitochondrial Complex I inhibitors EIPA and
      rotenone prevented increased acid production despite Extracellular Response
      Kinase activation and reduced sodium/hydrogen ion activity. Inhibition of Complex
      I prevented TRO's effects on glutamine metabolism. CONCLUSION: TRO induces
      cellular acidosis through Extracellular Signal-Regulated Kinase activation
      associated acid production and impaired acid extrusion. Acutely, increased acid
      production reflects mitochondrial Complex I proton pumping into the cytosol while
      chronically Complex I activity appears coupled to mitochondrial glutamate uptake
      and oxidation to ammonium at the expense of cytosolic transamination and alanine
      formation in these proximal tubule-like cells.

PMID- 19088430
TI  - Vasopressin regulates the phosphorylation state of AMP-activated protein kinase
      (AMPK) in MDCK-C7 cells.
AB  - AMP-activated protein kinase (AMPK) is a regulatory kinase coupling cellular
      metabolism with ion transport. Madin-Darby Canine Kidney-Clone 7 (MDCK-C7) cells
      possess characteristics of the renal principal cell type, express the cystic
      fibrosis transmembrane regulator and the epithelial Na(+) channel, and display
      NPPB and amiloride-sensitive transepithelial transport when stimulated with
      [Arg(8)]-vasopressin. [Arg(8)]-vasopressin binding to its receptor on the
      basolateral membrane of MDCK-C7 results in cAMP production, activation of cAMP
      dependent protein kinase A (PKA), and increases in Cl(-) and Na(+) transport.
      Ussing-style electrophysiology showed that the PKA inhibitor, H89, blocked Cl(-)
      and Na(+) transport. Unexpectedly, [Arg(8)]-vasopressin stimulation resulted in
      the dephosphorylation of pAMPK(thr172). H89 did not prevent this, suggesting that
      the dephosphorylation is independent of PKA. 24 hour, but not 15 minute,
      incubation with the AMPK activator, AICAR, also blocked [Arg(8)]-vasopressin
      stimulated currents. Contrary to previous studies, immunoblotting revealed that
      AICAR did not increase abundance of the active, phosphorylated form of AMPK
      (pAMPK(thr172)); although, AICAR treatment significantly blocked [Arg(8)]
      vasopressin -stimulated cAMP production. [Arg(8)]-vasopressin still caused
      pAMPK(thr172) dephosphorylation in the presence of AICAR, suggesting that this
      effect is also independent of cAMP. In summary, these data suggest [Arg(8)]
      vasopressin regulates AMPK phosphorylation and that AICAR inhibits ion transport
      independently of AMPK in MDCK-C7 cells.

PMID- 19088431
TI  - Modulation of Src activity by low molecular weight protein tyrosine phosphatase
      during osteoblast differentiation.
AB  - BACKGROUND: Src kinase plays a critical role in bone metabolism, particularly in
      osteoclasts. However, the ability of Src kinase to modulate the activity of other
      bone cells is less well understood. In this work, we examined the expression and
      activity of Src and low molecular weight protein tyrosine phosphatase (LMWPTP)
      during osteoblast differentiation and assessed the modulation of Src kinase by
      LMWPTP. METHODS: Differentiation of MC3T3-E1 pre-osteoblasts was induced by
      incubation with ascorbic acid and beta-glycerophosphate for up to 28 days. Src
      phosphorylation and LMWPTP expression were analyzed by immunoblotting. Src
      dephosphorylation in vitro was assessed by incubating immunoprecipitated Src with
      LMWPTP followed by assay of the residual Src activity using Sam68 as substrate.
      The importance of LMWPTP in Src dephosphorylation was confirmed by silencing pre
      osteoblasts with siRNA-LMWPTP and then assessing Src phosphorylation. RESULTS:
      Pre-osteoblast differentiation was accompanied by a decrease in phosphorylation
      of the activator site of Src and an increase in phosphorylation of the inhibitory
      site. The expression of total Src was unaltered, indicating that post
      translational modifications play a pivotal role in Src function. LMWPTP
      expression was higher in periods when the activator site of Src was
      dephosphorylated. LMWPTP dephosphorylated pY(527)-Src and pY(416)-Src in vitro,
      with greater specificity for pY(527)Src. Activation of LMWPTP produced strong
      activation of Src mediated by fast dephosphorylation of pY(527)-Src, followed by
      slower deactivation of this kinase via dephosphorylation of pY(416)Src.
      CONCLUSION: These results provide new insight into the mechanisms governing the
      dynamics of Src activity during osteoblast differentiation. A fuller
      understanding of these mechanisms will improve our knowledge of bone metabolism
      and of the regulation of Src in other types of cells.

PMID- 19088432
TI  - An incoherent magnetic field inhibited EGF receptor clustering and
      phosphorylation induced by a 50-Hz magnetic field in cultured FL cells.
AB  - Previously, we found that exposure to a 50-Hz magnetic field (MF) at 0.4 mT could
      induce epidermal growth factor (EGF) receptor clustering in Chinese hamster lung
      (CHL) fibroblast cells and superposition of an incoherent MF with the same
      intensity could inhibit the effect. In the present experiment, we investigated
      the effects of 50-Hz MF exposure at different intensities on EGF receptor
      clustering and phosphorylation in human amniotic cells (FL), and explored the
      interaction effect of an incoherent MF. Clustering and phosphorylation of EGF
      receptors on cellular membrane surface were analyzed using immunofluorescence
      assessed by confocal microscopy and western blot technology, respectively. EGF
      treatment served as a positive control. The results showed that, compared with
      sham exposure, exposure to a 50-Hz MF at 0.1, 0.2 or 0.4 mT for 15 min could
      significantly induce EGF receptor clustering and enhance phosphorylation on
      tyrosine-1173 residue in FL cells, whereas exposure to a 0.05 mT field for 15 min
      did not caused a significant effect. Exposure to an incoherent MF (frequency
      range between 30 to 90 Hz) at 0.2 mT for the same time neither induced EGF
      receptor clustering nor enhanced phosphorylation of EGF receptor in FL cells.
      When superposed, the incoherent MF at 0.2 mT completely inhibited EGF receptor
      clustering and phosphorylation induced by a 50-Hz MF at 0.1 and 0.2 mT. However,
      the incoherent MF could not completely eliminate the effects induced by a 0.4 mT
      50-Hz MF. Based on the results of this experiment, we conclude that membrane
      receptors could be one of the main targets where extremely-low frequency (ELF) MF
      interacts with cells, and the intensity threshold, in the case of EGF receptors,
      is between 0.05 and 0.1 mT. An incoherent MF could completely inhibit the effects
      induced by an ELF-MF of equal or lower intensity.

PMID- 19088433
TI  - Transcriptional regulation of HMG-CoA synthase and HMG-CoA reductase genes by
      human ACBP.
AB  - The acyl-CoA binding protein (ACBP) is an ubiquitary expressed multi-functional
      protein which regulates basic cellular functions such as fatty acid and steroid
      metabolism. Since ACBP is described to interact with the transcription factor
      hepatocyte nuclear factor 4 alpha (HNF-4alpha), we investigated the role of human
      ACBP on transcriptional regulation of the putative HNF-4alpha target gene HMG-CoA
      synthase 1 (HMGCS1). As shown by promoter-reporter assays ACBP represses the HNF
      4alpha-induced activity of a 617bp HMGCS1 promoter fragment by approximately 80%
      in HepG2 cells as well as in non-endodermal HeLa cells devoid of HNF-4alpha.
      Interestingly, reporter assays without co-transfection of HNF-4alpha revealed
      that ACBP reduces the activity of the HMGCS1 promoter by about 60 to 80% in both
      cell lines. Activities of 417bp and 317bp HMGCS1 promoter fragments were 2.5 to 4
      fold decreased by ACBP. Concordantly, the levels of HMGCS1-mRNA and -protein were
      diminished to 60% and 70% in ACBP-expressing HeLa cells, respectively.
      Additionally, ACBP reduces the promoter activity and the mRNA levels of the
      cholesterogenic HMG-CoA reductase (HMGCR). In conclusion, we provide evidence
      that ACBP is a transcriptional regulator of the HMGCS1 and HMGCR genes encoding
      rate-limiting enzymes of cholesterol synthesis pathway.

PMID- 19088434
TI  - Nitric oxide and the release of lipoprotein lipase from white adipose tissue.
AB  - BACKGROUND/AIM: Lipoprotein lipase (LPL) is the main enzyme responsible for the
      distribution of circulating triacylglycerides in tissues. Its regulation via
      release from active sites in the vascular endothelium is poorly understood. In a
      previous study we reported that in response to acute immobilization (IMMO), LPL
      activity rapidly increases in plasma and decreases in white adipose tissue (WAT)
      in rats. In other stress situations IMMO triggers a generalized increase in
      nitric oxide (NO) production. METHODS/RESULTS: Here we demonstrate that in rats:
      1) in vivo acute IMMO rapidly increases NO concentrations in plasma 2) during
      acute IMMO the WAT probably produces NO via the endothelial isoform of nitric
      oxide synthase (eNOS) from vessels, and 3) epididymal WAT perfused in situ with
      an NO donor rapidly releases LPL from the endothelium. CONCLUSION: We propose the
      following chain of events: stress stimulus / rapid increase of NO production in
      WAT (by eNOS) / release of LPL from the endothelium in WAT vessels. This chain of
      events could be a new mechanism that promotes the rapid decrease of WAT LPL
      activity in response to a physiological stimulus.

PMID- 19088435
TI  - Human mesenteric adipose tissue plays unique role versus subcutaneous and omental
      fat in obesity related diabetes.
AB  - BACKGROUND/AIMS: Obesity is a common and rapidly growing health problem today.
      Obesity is characterized by the increase of body fat and an excess of total body
      fat and, in particular, visceral fat accumulation, is considered to be a risk
      factor for type 2 diabetes mellitus. To determine whether the malfunction of the
      mesenteric adipose tissue plays an important role in the diabetic related
      metabolic syndrome, in this study, lipolysis and gene expression in the
      subcutaneous, omental and mesenteric adipose tissue of the diabetic subjects were
      evaluated. METHODS: Lipolysis and real time PCR were utilized to determine
      adipocyte function. RESULTS: Basal adipose tissue glycerol release is higher in
      diabetics than that of the non diabetics in all three fat depots. Isoproterenol
      (ISO) significantly increases glycerol release in subcutaneous, omental and
      mesenteric adipose tissues of non diabetic subjects but it stimulated glycerol
      release was significantly impaired in all three fat depots of the diabetic
      subjects. Gene expression studies indicate that leptin, Peroxisome proliferator
      activated receptor-gamma (PPAR-gamma), Fatty acid translocase (FAT/CD36) and
      11beta-hydroysteroid dehydrogenase (HSD) gene expression were significantly up
      regulated in the mesenteric adipose tissue of the diabetic patients. CONCLUSION:
      Human mesenteric adipose tissue in obese diabetic subjects has high basal
      glycerol release and impaired isoproterenol stimulated glycerol release. The
      obesity-related gene expressions in the mesenteric adipose tissue are up
      regulated, suggesting that the alterations of these genes in mesentery adipose
      depot may play a critical role in insulin resistance of type 2 diabetes and
      metabolic syndrome.

PMID- 19088436
TI  - Gender dimorphism in high-fat-diet-induced insulin resistance in skeletal muscle
      of aged rats.
AB  - Muscle resistance to insulin plays a key role in the metabolic dysregulation
      associated to obesity. A pro-inflammatory and pro-oxidant status has been
      proposed to be the link between dietary obesity and insulin resistance. Given the
      gender differences previously found in mitochondrial function and oxidative
      stress, the aim of the present study was to investigate whether this gender
      dimorphism leads to differences in the development of high-fat-diet-induced
      insulin resistance in rat skeletal muscle. Male and female rats of 15 months of
      age were fed with a high-fat-diet (32% fat) for 14 weeks. Control male rats
      showed a more marked insulin resistance status compared to females, as indicated
      by the glucose tolerance curve profile and the serum insulin, resistin and
      adiponectin levels. High-fat-diet feeding induced an excess of body weight of
      16.2% in males and 38.4% in females, an increase in both muscle mitochondrial
      hydrogen peroxide production and in oxidative damage, together with a decrease in
      the Mn-superoxide dismutase activity in both genders. However, high-fat-diet fed
      female rats showed a less marked insulin resistance profile than males, higher
      mitochondrial oxygen consumption and cytochrome c oxidase activity, and a better
      capacity to counteract the oxidative-stress-dependent insulin resistance through
      an overexpression of both muscle UCP3 and GLUT4 proteins. These results point to
      a gender dimorphism in the insulin resistance status and in the response of
      skeletal muscle to high-fat-diet feeding which could be related to a more
      detrimental effect of age in male rats.

PMID- 19088437
TI  - Role of PPAR-gamma in the modulation of CD36 and FcgammaRII induced by LDL with
      low and high degrees of oxidation during the differentiation of the monocytic THP
      1 cell line.
AB  - Scavenger or Fcgamma receptors are important for capture and clearance of
      modified LDL particles by monocytes/macrophages. Uptake via scavenger receptors
      is not regulated by intracellular levels of cholesterol and in consequence,
      macrophages develop into foam cells in the arterial intima. The levels of
      scavenger receptor CD36 are increased in atherosclerotic lesions and there is
      evidence that some components of oxLDL auto-regulate the expression of this
      receptor. Fcgamma receptor expression is increased in cardiovascular diseases but
      it is not known weather their expression is regulated by oxLDL. The biological
      properties of oxLDLs vary depending on the degree of oxidation. In the present
      study we investigated the effect of LDL particles showing extensive or low
      oxidation (HoxLDL and LoxLDL) on the expression of CD36 and FcgammaRII in a human
      monocytic cell line (THP-1), differentiated or not to macrophage, and the
      involvement of PPARgamma. It was found that both forms of oxLDL are able to
      increase the expression of CD36 and FcgammaRII and that this effect is dependent
      on the degree of oxidation and of the stage of cell differentiation (monocyte or
      macrophage). We also showed that the increased expression of FcgammaRII is
      dependent on PPARgamma whereas that of the CD36 is independent of PPARgamma.

PMID- 19088438
TI  - A role for the extracellular calcium-sensing receptor in cell-cell communication
      in pancreatic islets of langerhans.
AB  - BACKGROUND: The extracellular calcium-sensing receptor (CaR) is expressed in many
      tissues that are not associated with Ca(2+) homeostasis, including the endocrine
      cells in pancreatic islets of Langerhans. We have demonstrated previously that
      pharmacological activation of the CaR stimulates insulin secretion from islet
      beta-cells and insulin-secreting MIN6 cells. METHODS: In the present study we
      have investigated the effects of CaR activation on MIN6 cell proliferation and
      have used shRNA-mediated CaR knockdown to determine whether the CaR is involved
      in the regulation of insulin secretion via cell-cell communication. RESULTS: CaR
      activation caused the phosphorylation and activation of the p42/44 MAPK
      signalling cascade, and this activation was prevented by the shRNA-induced down
      regulation of CaR mRNA expression. CaR activation also resulted in increased
      proliferation of MIN6 cells, consistent with the known role of the p42/44 MAPK
      system in the regulation of beta-cell proliferation. Down-regulation of CaR
      expression had no detectable effects on glucose-induced insulin secretion from
      MIN6 cells maintained as monolayers, but blocked the increases in insulin
      secretion that were observed when the cells were configured as three-dimensional
      islet-like structures (pseudoislets), consistent with a role for the CaR in cell
      cell communication in pseudoislets. CONCLUSION: It is well established that islet
      function is dependent on communication between islet cells and the results of
      this study suggest that the CaR is required for beta-cell to beta-cell
      interactions within islet-like structures.

PMID- 19088439
TI  - Resveratrol inhibits electrical activity and insulin release from insulinoma
      cells by block of voltage-gated Ca+ channels and swelling-dependent Cl- currents.
AB  - The phytostilbene resveratrol (RV) improves the metabolic state in animal models
      by increasing the insulin responsiveness of tissues and there is evidence that RV
      affects insulin secretion from native beta-cells and insulinoma cells. In whole
      cell patch clamp experiments on clonal rat INS-1E cells we used high
      extracellular glucose (20 mM), extracellular hypotonicity (30%) or tolbutamide
      (100 microM) to elicit membrane depolarizations and electrical activity.
      Application of RV (50 microM) repolarized the cells, terminated electrical
      activity and prevented the hypotonicity-induced depolarization. These effects
      were fully reversible and intermittent application of RV restored tolbutamide
      induced electrical activity after desensitization. Glucose-induced depolarization
      was counteracted by RV in presence of iberiotoxin (50 nM), showing that the RV
      effect does not depend on BK(Ca) channel activation. RV dose-dependently
      inhibited K(ATP) currents, L- and T-type Ca(2+) currents and swelling-dependent
      Cl(-) currents evoked by either hypotonicity or high extracellular glucose--ion
      conductances crucially involved in regulating the electrical activity of insulin
      secreting cells. We further show that RV blunts glucose-induced, but not basal
      insulin release. Our results indicate that RV counteracts/prevents stimulus
      induced cell membrane depolarization and electrical activity by blocking voltage
      gated Ca(2+)- and swelling-dependent Cl(-) currents despite the inhibition of
      K(ATP) currents.

PMID- 19088440
TI  - LSm4 associates with the plasma membrane and acts as a co-factor in cell volume
      regulation.
AB  - ICln is a ubiquitous, multifunctional protein with functions in cell volume
      regulation and RNA processing, and is thus part of an intricate protein network
      critically involved in the homoeostasis of cells. To better understand this vital
      protein network in health and disease it is fundamental to characterize the
      interactions between the physiological pathways in which ICln is involved, as
      well as the spatio-temporal regulation of these interactions. In this study, we
      focused on the interaction between the two best studied pathways in which ICln is
      involved--regulatory volume decrease and RNA processing--and asked, whether or
      not the RNA processing factor and ICln interaction partner LSm4 may also have a
      function in cell volume regulation in NIH3T3 fibroblasts or HEK293 Phoenix cells.
      To address this question, we studied in isotonic and hypotonic conditions by
      FRET, biochemistry and electrophysiology, the intracellular distribution of the
      RNA processing factor LSm4, its interaction with ICln, as well as the involvement
      of LSm4 in the activation of the swelling dependent anion and osmolyte channel
      IClswell. In isotonic conditions, LSm4 associates with ICln, and the plasma
      membrane. Hypotonic cell swelling leads to the dissociation of LSm4 from the
      plasma membrane, and from ICln. Over-expression of LSm4 affects the translocation
      of ICln to the cell membrane and markedly inhibits the activation kinetics and
      current density of IClswell. These findings indicate that LSm4 not only acts in
      RNA processing, but also as a co-factor in cell volume regulation.

PMID- 19088441
TI  - Modulation of the voltage-gated potassium channel Kv1.5 by the SGK1 protein
      kinase involves inhibition of channel ubiquitination.
AB  - The serum and glucocorticoid inducible kinase SGK1 is involved in dexamethasone
      induced inhibition of insulin secretion by increasing voltage-gated potassium
      channel (Kv) activity. SGK1 upregulates the Kv1.5 channel but the precise
      mechanism underlying the SGK1 dependent regulation of Kv1.5 has not been defined
      yet. The present study explored the signal transduction processes involved.
      Expression studies in Xenopus oocytes revealed that SGK1 promotes channel
      activity by interfering with the Nedd4-2 ubiquitination pathway, irrespective of
      the presence of putative SGK1 phosphorylation sites on Kv1.5. Expression of the
      ubiquitin ligase Nedd4-2 declined Kv1.5 currents by ubiquitinating and thereby
      reducing Kv1.5 plasma membrane expression. Increasing concentrations of SGK1
      gradually compensated the inhibiting effect of Nedd4-2 on Kv1.5. Enhanced Kv1.5
      surface abundance by SGK1 reflects decreased channel internalization as indicated
      by Brefeldin A experiments. In conclusion, Kv1.5 upregulation by SGK1 involves
      inhibition of channel ubiquitination by Nedd4-2 that leads to Kv1.5 stabilization
      in the plasma membrane. Our results suggest that the kinase might participate in
      the regulation of insulin secretion in part by controlling Kv1.5 surface
      abundance.

PMID- 19088442
TI  - A highly conserved alanine in the S6 domain of the hERG1 K+ channel is required
      for normal gating.
AB  - The central cavity of K(+)-selective ion channels is lined by four S6
      transmembrane alpha-helices. An Ala residue is located near the midpoint of each
      S6 and marks the narrowest point of the central cavity. In hERG1 channels, we
      determined the functional consequences of substituting this conserved Ala
      (Ala653) with other hydrophobic or charged amino acids. Mutant channels were
      expressed in Xenopus oocytes and ionic currents measured by using the two
      microelectrode voltage clamp technique. Substitution of Ala653 with bulkier
      hydrophobic residues (Val, Leu, Ile, Met, Phe, Trp) did not prevent ion
      conduction, but the mutant channels activated at more negative potentials
      compared to wild-type channels. The half-point for voltage dependent activation
      was shifted by -54 mV for the most conservative hydrophobic mutation, A653V.
      Oxidation of A653C hERG1 channels induced a maintained current at negative
      membrane potentials. This effect was not reversible with dithiothreitol,
      indicating that the sulfhydryl side-chains of Cys653 were oxidized to a
      negatively charged sulfinic or sulfonic acid. Substitution of Ala653 with acidic
      (Asp, Glu) or basic (Arg, Lys) residues prevented channel deactivation. Thus, an
      Ala at position 653 in hERG1 is required for normal voltage dependence of channel
      gating and a charged residue in this position prevents channel closure.

PMID- 19088443
TI  - Biophysical characterization of the short QT mutation hERG-N588K reveals a mixed
      gain-and loss-of-function.
AB  - The short QT syndrome is a newly discovered pro-arrhythmic condition, which may
      cause ventricular fibrillation and sudden death. Short QT can originate from the
      apparent gain-of-function mutation N588K in the hERG potassium channel that
      conducts repolarising I(Kr) current. The present study describes a profound
      biophysical characterization of HERG-N588K revealing both loss-of-function and
      gain-of-function properties of the mutant. Experiments were conducted after
      heterologous expression in both Xenopus laevis oocytes and mammalian cells and at
      both room temperature and at 37 degrees C. Also the impact of the beta-subunits
      KCNE2 was investigated. The most prominent loss-of-function property of HERG
      N588K was reduced tail currents but also the activation properties was
      compromised. Based on these biophysical results we suggest that the general view
      of HERG-N588K being a gain-of-function is modified to a mixed gain- and loss-of
      function mutation. This might also have impact on the pathological picture of the
      HERG-N588K channels ability to trigger arrhythmic events.

PMID- 19088444
TI  - Reduced calmodulin expression accelerates transient outward potassium current
      inactivation in diabetic rat heart.
AB  - BACKGROUND/AIMS: In myocytes from diabetic hearts, the reduction in the amplitude
      of the transient outward potassium current (I(to)) and the acceleration of its
      inactivation contribute to the action potential duration lengthening. Whereas the
      reduced amplitude is attributable to a reduced support of trophic factors, the
      mechanism underlying the acceleration of inactivation remains unknown.
      Ca(2+)/Calmodulin-dependent protein kinase II (CaMKII) modifies the inactivation
      kinetics of I(to). In this work we explored the role of CaMKII in the
      acceleration of I(to) current inactivation observed in diabetic myocytes.
      METHODS: We used patch-clamp and immunoblotting techniques in enzymatically
      isolated myocytes from healthy and streptozotocin-induced diabetic rat hearts,
      and in blood samples from diabetic patients. RESULTS: In control myocytes,
      inhibition of either calmodulin or CaMKII accelerated I(to) current inactivation.
      However, in diabetic myocytes I(to) inactivation was already accelerated, and did
      not respond to calmodulin or CaMKII inhibition. Calmodulin protein abundance was
      significantly reduced in diabetic myocytes. Incubation of diabetic myocytes with
      insulin recovered calmodulin expression to normal values. A similar pattern of
      calmodulin expression appears in the blood of diabetic patients. Insulin
      treatment also restored I(to) current inactivation kinetics as well as the
      responsiveness to regulation by calmodulin. CONCLUSION: Diabetes-induced
      acceleration of I(to) current inactivation is due to a reduced effect of CaMKII
      on I(to) channels as a result of a diabetes-induced reduction in calmodulin
      protein expression. A correct follow up of the insulin treatment could prevent
      this alteration.

PMID- 19088445
TI  - Post-conditioning preserves glycolytic ATP during early reperfusion: a survival
      mechanism for the reperfused heart.
AB  - BACKGROUND: Glycolytic activity during the transition period from anaerobic to
      aerobic metabolism has been demonstrated to be critical for heart recovery in
      isolated reperfused hearts. The purpose of this work was to investigate the
      relevance of the glycolytic pathway in preserving the cardiac function of post
      conditioned hearts. METHODS: The activation of the glycolytic pathway in post
      conditioned hearts was evaluated by measuring GLUT-4 insertion, glucose
      consumption and lactate production. Iodoacetic acid and 2-deoxy-D-glucose were
      administrated to the working hearts to evaluate the effect of glycolytic
      inhibition in the post-conditioning protective effect. RESULTS: Post-conditioning
      maneuvers applied to isolated rat hearts, after prolonged ischemia and before
      reperfusion, promoted recovery of cardiac mechanical function with sustained
      increase of GLUT-4 translocation and activation of the glycolytic pathway during
      ischemia and early reperfusion. Iodoacetate inhibited the protective effect of
      post-conditioning, without affecting the mitochondrial oxidative capacity.
      Glycolysis contribution to maintain mechanical function at early reperfusion was
      observed in post-conditioned hearts perfused with 2-deoxy-D-glucose and in hearts
      in which iodoacetate was administered only during reperfusion. CONCLUSION: It is
      concluded that in the post-conditioned heart, a functional compartmentation of
      anaerobic energy metabolism, at early reperfusion, plays a significant role in
      cardiac protection against reperfusion damage.

PMID- 19088446
TI  - The protective effect of Egr-1 antisense oligodeoxyribonucleotide on myocardial
      injury induced by ischemia-reperfusion and hypoxia-reoxygenation.
AB  - AIMS: Our previous studies have shown that myocardial ischemia-reperfusion (I/R)
      injury is related closely with early growth response (Egr)-1 overexpression. The
      present study is to confirm thoroughly the effects of Egr-1 on the occurrance and
      development of myocardial I/R injury. METHODS: The Sprague-Dawley rat myocardial
      I/R model and cultured cardiomyocyte hypoxia-reoxygenation (H/R) model were
      established. The synthesized Egr-1 antisense oligodeoxyribonucleotide (AS-ODN)
      was transfected into myocardial tissues and cells. Hemodynamic parameters,
      myeloperoxidase (MPO), cardiac troponin I (cTnI), tumor necrosis factor-alpha
      (TNF-alpha), morphology, spontaneous beat and cell viability were measured to
      assess the degree of injury and inflammation of myocardial tissues and cells.
      RESULTS: In vivo, Egr-1 AS-ODN significantly attenuated injury and inflammation
      of myocardial tissues caused by I/R evidenced by the amelioration of hemodynamics
      and the reduction in MPO activity. In vitro, Egr-1 AS-ODN significantly relieved
      injury and inflammation of cultured cardiomyocyte caused by H/R evidenced by the
      improvement in morphology, structure and beat as well as the decrease in leakage
      of cTnI and release of TNF-alpha from cultured cardiomyocyte. CONCLUSIONS: These
      data suggest that Egr-1 plays a vital role in the pathogenesis of myocardial I/R
      injury and Egr-1 AS-ODN could protect the myocardium from I/R injury.

PMID- 19088447
TI  - SRIF receptor subtype expression and involvement in positive and negative
      contractile effects of somatostatin-14 (SRIF-14) in ventricular cardiomyocytes.
AB  - BACKGROUND/AIMS: Somatostatin-14 (SRIF-14), a neuropeptide co-stored with
      acetylcholine in the cardiac parasympathetic innervation, exerts both positive
      and negative influences directly on contraction of ventricular cardiomyocytes,
      indicative of involvement of more than one of five known SRIF (SSTR) receptor
      subtypes. The aim was to characterize receptor subtype expression in adult rat
      ventricular cardiomyocytes and to investigate the influence of a series of SRIF
      (SSTR) subtype-selective agonists on contractile parameters. METHODS: mRNA and
      protein expression of each receptor subtype were quantified by RT-PCR and
      immunoblotting respectively; for contraction studies, cells were stimulated at
      0.5 Hz under basal conditions and in the presence of isoprenaline (ISO, 10(-8)M).
      RESULTS: all five SRIF (SSTR) receptor subtypes were expressed in cardiomyocytes
      although SRIF1A (SSTR2) and SRIF2A (SSTR1) were less abundant than the other
      subtypes. L803087 (10(-8)M), a SRIF2B (SSTR4) agonist, attenuated ISO-stimulated
      peak contractile amplitude and prolonged relaxation time (T(50)). L796778 (10(
      7)M), a SRIF1C (SSTR3) agonist, augmented basal and ISO-stimulated peak
      contractile amplitude; L779976 (10(-8)M) and L817818 (10(-9)M), agonists at
      SRIF1A (SSTR2) and SRIF1B (SSTR5) receptors, respectively, also augmented ISO
      stimulated peak amplitude. CONCLUSION: These data support involvement of SRIF2B
      (SSTR4) receptors in the negative contractile effects of SRIF-14, while one or
      more of the three SRIF1 receptor subtypes (SSTR2, 3 or 5) may contribute to the
      positive contractile effects of SRIF-14.

PMID- 19088448
TI  - Entrapment of embryonic stem cells-derived cardiomyocytes in macroporous
      biodegradable microspheres: preparation and characterization.
AB  - Embryonic Stem (ES) cells-derived cardiomyocytes can possibly be applied for cell
      therapy of diseases such as heart failure. Biodegradable scaffolds will
      significantly improve the expansion of sufficient functional ES cell-derived
      cardiomyocytes and may also increase the survival rate of cardiomyocytes after
      their transplantation. In the present study, we cultivated cardiomyocytes
      isolated from a transgenic a-myosin heavy chain (alpha-MHC) ES cell lineage
      expressing both puromycin resistance and enhanced green fluorescent protein
      (EGFP) under the control of the alpha-MHC promoter in macroporous gelatine
      microspheres using small-scale bioreactors and proved that cardiomyocytes
      function after their cultivation in micropsperes. The average number of
      cultivated cells per microsphere was optimised once the most suitable agitation
      conditions and the optimal timeframe of cultivation were identified. Our study
      shows that 72% of CultiSpher-S beads were colonised by cardiomyocytes under
      optimal conditions. Scanning electron microscopy (SEM) and confocal laser
      scanning microscopy (CLSM) showed that colonization of the beads was not limited
      to the surface, but that cells also invaded the inner surfaces of the
      microspheres. Electrophysiological experiments demonstrated that the action
      potentials (APs) of alpha-MHC(+) cardiomyocytes entrapped in microspheres were
      identical to action potentials of control cells. This attractive approach for
      cultivation and expansion of functional cardiomyocytes in biodegradable
      macroporous may offer a perspective for higher transplantation efficiencies of ES
      cell-derived cardiomyocytes.

PMID- 19088449
TI  - Role of interleukin-6 in the control of DNA synthesis of hepatocytes: involvement
      of PKC, p44/42 MAPKs, and PPARdelta.
AB  - Interleukin-6 (IL-6) is a pleiotropic cytokine with a pivotal role in normal
      hepatic growth and liver regeneration. Therefore, in the present study, we
      examined the effect of IL-6 on cell proliferation and the related signaling
      pathways in primary cultured chicken hepatocytes. IL-6 increased the level of
      [(3)H]thymidine incorporation in a time (>or= 6 hr)- and a dose (>or= 0.1 ng/ml)
      dependent manner. Indeed, IL-6 increased the number of BrdU-positive cells and
      the total number of cells. IL-6 (10 ng/ml) increased the level of IL-6Ralpha and
      glycoprotein (gp) 130 (IL-6Rbeta) protein expression, Janus Kinase (JAK) 2,
      signal transducer and activator of transcription (STAT) 3, PKC, p44/42 MAPKs
      phosphorylation, and PPARdelta protein expression. Inhibition of each pathways
      blocked IL-6-induced [(3)H]thymidine incorporation increase. IL-6 increased c
      fos, c-jun, and c-myc proto-oncogene mRNA levels and the percentage of cells in
      the S phase according to fluorescence-activated cell sorter (FACS) analysis. IL-6
      induced G1/S phase progression was inhibited by AG 490 (2x10(-5) M, JAK2
      inhibitor), a STAT3 inhibitor peptide (10(-5) M), bisindolylmaleimide I (10(-6)
      M, PKC inhibitor), PD 98059 (10(-5) M, p44/42 MAPKs blocker), or PPARdelta
      specific small interfering RNAs (siRNAs). In conclusion, IL-6 stimulates the
      proliferation of primary cultured chicken hepatocytes through PKC, p44/42 MAPKs,
      and PPARdelta pathways.

PMID- 19088450
TI  - Activation of the CFTR Cl- channel by trimethoxyflavone in vitro and in vivo.
AB  - The flavone apigenin has been previously selected as a potent pharmacological
      activator of the CFTR Cl(-) channel, however, its utility for the activation of
      CFTR in vivo is expected to be limited because flavonoids are readily
      metabolized. We therefore investigated the poorly metabolizable methylether of
      apigenin, 5,7,4'-trimethoxyflavone (TMF) as a CFTR activator using
      transepithelial short-circuit current measurements, whole cell and single cell
      patch clamp techniques, and nasal potential difference (PD) measurements.
      Transepithelial Cl(-) secretion by Calu-3 epithelia was stimulated by TMF with a
      halfmaximal concentration of 64+/-5 microM to 55+/-15% of maximal currents
      achieved by subsequent addition of cAMP agonist forskolin (10 microM). In
      forskolin-prestimulated tissues, TMF showed small effects and stimulated Cl(-)
      secretion by an additional 6%. Single channel and whole cell patch clamp
      techniques were used to verify these effects and identify CFTR as the target of
      TMF. TMF increased the open probability of silent CFTR (to 0.31+/-0.06) but
      showed small effects once CFTR had been prestimulated with forskolin. In nasal PD
      measurements in humans, perfusion of TMF onto the nasal mucosa activated nasal PD
      by -9.5+/-1.1 mV, which was 69% of the effect of TMF+isoproterenol (-13.8+/-3.9
      mV). These data show that TMF is an activator of CFTR in both in vitro and in
      vivo assays that targets mainly the unstimulated CFTR.

PMID- 19088451
TI  - Elevated intracellular calcium stimulates NHE3 activity by an IKEPP (NHERF4)
      dependent mechanism.
AB  - The ileal brush border (BB) contains four evolutionarily related multi-PDZ domain
      proteins including NHERF1, NHERF2, PDZK1 (NHERF3) and IKEPP (NHERF4). Why
      multiple related PDZ proteins are in a similar location in the same cell is
      unknown. However, some specificity in regulation of NHE3 activity has been
      identified. For example, elevated intracellular Ca(2+) ([Ca(2+)](i)) inhibition
      of NHE3 is reconstituted by NHERF2 but not NHERF1, and involves the formation of
      large NHE3 complexes. To further evaluate the specificity of the NHERF family in
      calcium regulation of NHE3 activity, the current study determined whether the
      four PDZ domain containing protein IKEPP reconstitutes elevated [Ca(2+)](i)
      regulation of NHE3. In vitro, IKEPP bound to the F2 region (aa 590-667) of NHE3
      in overlay assays, which is the same region where NHERF1 and NHERF2 bind. PS120
      cells lack endogenous NHE3 and IKEPP. Treatment of PS120/NHE3/IKEPP cells (stably
      transfected with NHE3 and IKEPP) with the Ca(2+) ionophore, 4-Br-A23187 (0.5
      microM), stimulated NHE3 V(max) activity by approximately 40%. This was
      associated with an increase in plasma membrane expression of NHE3 by a similar
      amount. NHE3 activity and surface expression were unaffected by A23187 in
      PS120/NHE3 cells lacking IKEPP. Based on sucrose density gradient centrifugation,
      IKEPP was also shown to exist in large complexes, some of which overlap in size
      with NHE3, and the size of both NHE3 and IKEPP complexes decreased in parallel
      after [Ca(2+)](i) elevation. FRET experiments on fixed cells demonstrated that
      IKEPP and NHE3 directly associated at an intracellular site. Elevating
      [Ca(2+)](i) decreased this intracellular NHE3 and IKEPP association. In summary:
      (1) In the presence of IKEPP, elevated [Ca(2+)](i) stimulates NHE3 activity. This
      was associated with increased expression of NHE3 in the plasma membrane as well
      as a shift to smaller sizes of NHE3 and IKEPP containing complexes. (2) IKEPP
      directly binds NHE3 at its F2 C-terminal domain and directly associates with NHE3
      in vivo (FRET). (3) Elevated [Ca(2+)](i) decreased the association of IKEPP and
      NHE3 in an intracellular compartment. Based on which NHERF family member is
      expressed in PS120 cells, elevated [Ca(2+)](i) stimulates (IKEPP), inhibits
      (NHERF2) or does not affect (NHERF1) NHE3 activity. This demonstrates that
      regulation of NHE3 depends on the nature of the NHERF family member associating
      with NHE3 and the accompanying NHE3 complexes.

PMID- 19088452
TI  - The peptide transporter PEPT2 is targeted by the protein kinase SGK1 and the
      scaffold protein NHERF2.
AB  - PEPT1 and PEPT2 are members of the family of proton-dependent oligopeptide
      transporters that mediate electrogenic uphill transport of small peptides and
      peptidomimetics into a variety of cells. Kinetic properties and substrate
      recognition sites of those transporters have been well defined previously. Little
      is known, however, about regulation of those transporters. Both PEPT isoforms
      contain putative phosphorylation sites for the serum and glucocorticoid inducible
      kinase SGK1 and a C-terminal PDZ binding motif that might be recognized by PDZ
      domains of the Na(+)/H(+) exchanger regulatory factors NHERF1 and NHERF2. Thus,
      the present study attempted to clarify the role of SGK1 and NHERFs in the
      modulation of PEPT isoforms. Expression studies in Xenopus oocytes with
      subsequent electrophysiology and immunoassays revealed that SGK1 and NHERF2, but
      not the NHERF1 isoform specifically enhance PEPT2 function and surface abundance.
      The kinase is effective through phosphorylation of (185)Ser within the SGK1
      consensus site, since disruption of this site prevented transporter modulation by
      the kinase. NHERF2 failed to regulate the C-terminal deletion mutant
      (PEPT2DeltaC) indicating that the C-terminal PDZ-binding motif in PEPT2 governs
      transport modulation by NHERF2. Coexpression of NHE3 stimulates PEPT2 activity to
      a similar extent as coexpression of NHERF2. Dynasore experiments demonstrated
      that SGK1 and NHERF2 activate PEPT2 by stabilizing the transporter at the cell
      surface. In conclusion, the present results reveal two novel PEPT2
      posttranslational modulators, SGK1 and NHERF2, which might regulate transport of
      oligopeptides and peptidomimetic drugs.

PMID- 19088453
TI  - Lipopolysaccharide induces inhibition of galactose intestinal transport in
      rabbits in vitro.
AB  - BACKGROUND/AIMS: Previous studies from our laboratory have revealed impaired
      intestinal absorption of D-galactose in lipopolysaccharide-treated rabbits. The
      aim of the present work was to examine the effect of LPS on D-galactose
      intestinal absorption in vitro. METHODS: D-galactose intestinal transport was
      assessed employing three techniques: sugar uptake in rings of everted jejunum,
      transepithelial flux in Ussing-type chambers and transport assays in brush border
      membrane vesicles. The level of expression of the Na(+)/D-galactose cotransporter
      (SGLT1) was analyzed by Western blot. RESULTS: LPS decreased the mucosal D
      galactose transport in rabbit jejunum but a preexposition to the endotoxin was
      required. LPS affected the Na(+)-dependent transport system by increasing the
      apparent Km value without affecting the Vmax. It also decreased the Na(+), K(+)
      ATPase activity. However, it did not inhibit neither the uptake of D-galactose by
      brush border membrane vesicles nor modified the SGLT1 protein levels in the brush
      border, suggesting an indirect endotoxin effect. This inhibitory effect, was
      reduced by selective inhibitors of Ca(2+)-calmodulin (W13), protein kinase C (GF
      109203X), p38 mitogen-activated protein kinase (SB 203580), c-Jun N-terminal
      kinase (SP 600125) and mitogen extracellular kinase (U 0126). CONCLUSION: LPS
      inhibits the mucosal Na(+)-dependent D-galactose intestinal absorption and the
      Na(+), K(+)-ATPase activity when it is added to the tissue. Intracellular
      processes related to protein kinases seem to be implicated in the endotoxin
      effect.

PMID- 19088454
TI  - Role of PDK1 in regulation of gastric acid secretion.
AB  - Pharmacological inhibition of phosphoinositide 3-kinase (PI3K) has previously
      been shown to enhance basal gastric acid secretion. Signaling of PI-3-kinase
      includes activation of the phosphoinositide dependent kinase PDK1. We thus
      hypothesized that PDK1 may influence gastric acid secretion. In the present study
      gastric acid secretion in mice expressing n20 % of PDK1 (pdk1(hm)) was compared
      to gastric acid secretion in their wild type littermates (pdk1(wt)). According to
      BCECF-fluorescence cytosolic pH in isolated gastric glands was similar in
      pdk1(hm) and in pdk1(wt) mice. Na(+)-independent pH recovery (DeltapH/min)
      following an ammonium pulse, which reflects K(+)/H(+)-ATPase activity, was
      however, significantly faster in pdk1(hm) than in pdk1(wt) mice. In both
      genotypes, DeltapH/min was abolished in the presence of K(+)/H(+)-ATPase
      inhibitor omeprazole (100 microM). Increase of local K(+)-concentrations to 35 mM
      (replacing Na(+)/NMDG) significantly increased DeltapH/min in both, pdk1(hm) and
      pdk1(wt) mice, and abrogated the differences between genotypes. Similarly,
      treatment with 5 microM forskolin as well as stimulation of protein kinase C with
      phorbolester phorbol 12 myristate 13 acetate (100 nM) enhanced DeltapH/min to
      almost identical values in pdk1(hm) and in pdk1(wt)mice. Protein kinase A
      inhibitor H89 (50 nM) decreased DeltapH/min in pdk1(hm) to values similar to
      those in pdk1(wt). In conclusion, deficient activity of PDK1 leads to a marked
      increase of gastric acid secretion. The present observations thus disclose a
      novel element in the regulation of gastric H(+) secretion.

PMID- 19088455
TI  - Phosphatidylinositide dependent kinase deficiency increases anxiety and decreases
      GABA and serotonin abundance in the amygdala.
AB  - Pathological anxiety is paralleled by deficits in serotonergic and GABAergic
      neurotransmission in the amygdala. Conversely, anxiety disorders and depression
      may be reversed by brain-derived neurotrophic factor (BDNF). BDNF signaling
      involves Phosphatidylinositol 3-Kinase / 3-phosphoinositide-dependent protein
      kinase 1 (PI3K/PDK1). We thus hypothesized that impaired function of PDK1 might
      be associated with increased anxiety and concomitant neurotransmitter changes.
      Here we used the hypomorphic PDK1(hm) mouse to investigate anxiety behavior in
      different settings: PDK1(hm) mice differed from Wt littermates PDK1(WT) in
      several behavioral measures related to anxiety and exploration, namely in the
      open field, dark-light box, O-maze and startle response. Further we analyzed the
      brain substrate underlying this phenotype and found significantly decreased GABA,
      taurine and serotonin concentrations in the amygdala and olfactory bulb of
      PDK1(hm) mice, while BDNF and nerve growth factor (NGF) concentrations were not
      significantly different between PDK1(hm) and PDK1(WT) mice. These results suggest
      that impaired PI3K signaling in the PDK1(hm) mouse reduces concentrations of GABA
      and serotonin in anxiety related brain regions and can serve as a molecular
      substrate for behavior indicative for anxious and depressive-like mood states.

PMID- 19088457
TI  - Differences in mitochondrial function and antioxidant systems between regions of
      human glioma.
AB  - Metabolic features and oxidative stress have been extensively studied in cancer
      cells. However, comparative studies between cancer cell populations that coexist
      in human neoplastic tissue are not frequently available. The aim of the present
      study was to characterize markers of oxidative status and mitochondrial function
      in center vs. periphery of human fresh glioma samples; therefore, antioxidant
      systems, oxidative stress and mitochondrial parameters were assessed in gross
      total resections of gliomas. Mitochondrial protein and mitochondrial DNA content,
      enzymatic activities of mitochondrial oxidative and phosphorylative system,
      antioxidant mechanisms, mitochondrial H(2)O(2) production, oxygen consumption and
      cellular oxidative damage were measured in human gliomas. Concentric regions of
      human glioma tissue showed similar mitochondrial structural markers; conversely,
      the functionality of their isolated mitochondria was significantly different. In
      this way, the tumor periphery exhibited higher respiratory rate and fewer
      antioxidant systems than tumor center. Our results have expanded previous
      investigations, which report the presence of cell populations with different
      oxidative susceptibility in human brain tumor samples. This is, to our knowledge,
      the first study to investigate metabolic differences in concentric regions of
      gross total resections of glioma. Interestingly, the cancer cell population that
      exhibits an increased antioxidant capacity within the tumor mass might be
      responsible for tumor resistance to chemotherapy and radiotherapy.

PMID- 19088456
TI  - Neuroinflammation activates Mdr1b efflux transport through NFkappaB: promoter
      analysis in BBB endothelia.
AB  - BACKGROUND/AIMS: Although it is known that drug delivery across the blood-brain
      barrier (BBB) may be hampered by efflux transport activity of the multidrug
      resistance (mdr) gene product P-glycoprotein, it is not clear how inflammation
      regulates efflux transporters. In rat brain endothelial (RBE4) cells of BBB
      origin, the proinflammatory cytokine TNF mainly induced transcriptional
      upregulation of mdr1b, and to a lesser extent mdr1a, resulting in greater efflux
      of the substrates. This study further determines the mechanisms by which TNF
      activates mdr1b promoter activity. METHODS/RESULTS: Luciferase reporter assays
      and DNA binding studies show that (1) maximal basal promoter activity was
      conferred by a 476 bp sequence upstream to the mdr1b transcriptional initiation
      site; (2) TNF induced upregulation of promoter activity by NFkappaB nuclear
      translocation; and (3) the NFkappaB binding site of the mdr1b promoter was solely
      responsible for basal and TNF-activated gene transcription, whereas the p53
      binding site was not involved. Binding of the p65 subunit of NFkappaB to nuclear
      DNA from RBE4 cells was shown by electrophoretic mobility shift assay and
      chromatin immunoprecipitation assays. CONCLUSION: NFkappaB mediates TNF-induced
      upregulation of mdr1b promoter activity, illustrating how inflammation activates
      BBB efflux transport.

PMID- 19088458
TI  - Alpha--lipoic acid decreases DNA damage and oxidative stress induced by alcohol
      in the developing hippocampus and cerebellum of rat.
AB  - BACKGROUND/AIMS: The present study was initiated in order to investigate the
      protective effects of alpha-lipoic acid upon ethanol-induced DNA damage, lipid
      peroxidation and protein oxidation in the developing rat hippocampus and
      cerebellum. METHODS: Pregnant Wistar rats received ethanol with, or without
      lipoic acid from gestation day (GD) 7 throughout lactation. The changes in DNA
      damage, protein carbonyl, lipid hydroperoxide, catalase and superoxide dismutase
      activities were measured in the hippocampus and cerebellum of male offspring at
      the end of the lactation period. RESULTS: The results indicated that DNA damage,
      lipid peroxidation and protein oxidation in the hippocampus and cerebellum were
      significantly elevated in animals that received alcohol. However, the catalase
      and superoxide dismutase activity results showed patterns that differed from
      those of DNA damage, lipid peroxidation and protein oxidation. Lipoic acid
      treatment significantly decreased DNA damage compared with the group that were
      administered alcohol alone, and restored the elevated protein carbonyl and lipid
      hydroperoxide levels to the levels of the control group. CONCLUSIONS: Our
      findings confirm that oxidative stress and DNA damage occur in the developing
      hippocampus and cerebellum as a result of alcohol administration, and also
      suggest that lipoic acid has protective effects as an antioxidant against alcohol
      induced disorders in the developing hippocampus and cerebellum.

PMID- 19088459
TI  - Effects of various dietary arginine and lysine concentrations on plasma and liver
      cholesterol concentrations in rats.
AB  - BACKGROUND: It has been hypothesized that the arginine:lysine ratio of dietary
      proteins influences cholesterol concentrations in plasma and liver of men and
      animals. This study was performed to test this hypothesis in rats by using diets
      with various concentrations of arginine and lysine, differing in their
      arginine:lysine ratios. METHODS: Two experiments with growing rats were
      performed, some of which received diets containing 4.5, 9 or 18 g arginine/kg and
      9 or 18 g lysine/kg, respectively, for a period of 21 days. In the first
      experiment, a cholesterol-free diet was used; in the second experiment, a diet
      supplemented with cholesterol and sodium cholate as hypercholesterolaemic
      compounds was used. RESULTS: In experiment 1, increasing the arginine
      concentration lowered HDL and plasma cholesterol concentration; however,
      cholesterol concentrations in liver, LDL and VLDL remained unchanged. In
      experiment 2, increasing the arginine concentration lowered HDL cholesterol and
      increased liver cholesterol (p<0.05); cholesterol concentrations in plasma, LDL
      and VLDL remained unchanged. The only effect of the dietary lysine concentration
      concerned the effect on VLDL and liver cholesterol concentration, which were both
      lower in rats fed the diets with 18 g lysine/kg than in those fed the diets with
      9 g lysine/kg (p<0.05). Varying the dietary arginine:lysine ratio between 0.25
      and 2.0 had no influence on cholesterol concentration in LDL and VLDL in both
      experiments; HDL cholesterol concentration was lowered by increasing this ratio
      (p<0.05). CONCLUSION: The present study does not support the hypothesis that an
      increase in the dietary arginine:lysine ratio causes hypocholesterolaemic effects
      in rats.

PMID- 19088460
TI  - Surgical removal of perirenal and epididymal adipose tissue decreases serum
      leptin concentration and increases lipogenic enzyme activities in remnant adipose
      tissue of old rats.
AB  - BACKGROUND: The rate of lipogenesis and gene expression of lipogenic enzymes in
      white adipose tissue (WAT) of rats decreases with age. Previously, we showed the
      inverse relationship between serum leptin concentration and lipogenic enzymes
      activities in WAT of ageing rats. Based on those results, we postulated that
      leptin could play some role in the downregulation of lipogenic enzyme genes
      expression in WAT of old rats. OBJECTIVE: To further test this hypothesis, in the
      present paper we examined the effect of surgical removal of perirenal and
      epididymal WAT on serum leptin concentration and lipogenic enzymes activities in
      remnant adipose tissue of old rats. METHODS: One-year-old rats, which display a
      high serum leptin concentration and low lipogenic enzyme activities in WAT, were
      subjected to surgical removal of the perirenal and epididymal WAT. Two months
      after the surgery, the serum leptin concentration and lipogenic enzyme activities
      in remnant WAT were compared to the serum leptin concentration and lipogenic
      enzyme activities measured in adipose tissue collected during the surgery.
      RESULTS: WAT removal resulted in an approximately 6-fold decrease of serum leptin
      concentration and about a 2-fold increase of lipogenic enzyme activities in
      remnant adipose tissue. CONCLUSIONS: These results indicate that interventions
      designed to reduce abdominal adipose tissue mass can change the lipogenic
      activity of remnant adipose tissue. Additionally, leptin could be one of the
      factors contributing to the downregulation of the genes expression of lipogenic
      enzymes during ageing in rats.

PMID- 19088461
TI  - Clinical and immunological follow-up of pemphigus patients on adjuvant treatment
      with immunoadsorption or rituximab.
AB  - BACKGROUND: Pemphigus vulgaris (PV) is a life-threatening autoimmune blistering
      skin disease which is associated with pathogenic IgG autoantibodies against
      desmogleins (Dsg) 1 and 3. Novel therapeutic strategies such as immunoadsorption
      (IA) or the anti-CD20 antibody rituximab (Rtx) hold promise to be effective in
      severe or recalcitrant PV. PATIENTS AND METHODS: In the present retrospective
      study, 6 patients with extensive cutaneous PV were subjected to adjuvant IA
      treatment while 5 patients with severe mucosal PV received adjuvant Rtx
      treatment. RESULTS: Within 6 months, IA and Rtx induced excellent clinical
      responses which were associated with a significant reduction of prednisolone
      doses and a decrease in anti-Dsg-specific IgG. Over a 12-month period, 3 IA
      treated patients required additional adjuvant drugs while all of the PV patients
      on Rtx had no or only minimal residual symptoms. CONCLUSION: The relative
      therapeutic (long-term) efficacy of IA and Rtx in cutaneous versus mucosal PV
      needs to be evaluated in a prospective study.

PMID- 19088462
TI  - Health-related quality of life in patients with neurofibromatosis type 1. A
      survey of 129 Italian patients.
AB  - BACKGROUND/AIMS: Neurofibromatosis type 1 (NF1), a genetic condition most
      commonly characterized by the presence of dermal neurofibromas and cafe au lait
      macules, has a significant impact upon quality of life (QoL). The study aimed to
      assess the impact of NF1 on QoL. METHODS: A total of 129 patients with NF1
      completed the study questionnaires in an Italian academic dermatological centre
      and a neurofibromatosis clinic at the University of Rome. RESULTS: All domains of
      general-health-related QoL were affected. Patients with serious cosmetic problems
      reported a greater impact on the emotional domain. CONCLUSION: In our study, the
      impact of the cosmetic features on QoL had the greatest importance. This survey
      demonstrates the usefulness of QoL measurements in supplementing clinical
      assessments.

PMID- 19088463
TI  - Systemic lupus erythematosus presenting with Kikuchi-Fujimoto's disease as a long
      term sequela of drug-induced hypersensitivity syndrome. A possible role of
      Epstein-Barr virus reactivation.
AB  - Drug-induced hypersensitivity syndrome (DIHS) is a severe form of drug eruptions
      associated with viral reactivations. Autoimmune diseases have been reported to
      develop several months or years after the resolution of DIHS. We describe a 36
      year-old man with cervical lymphadenopathy and an erythematous eruption affecting
      the face and neck, which evolved into clinically evident systemic lupus
      erythematosus. He had had an episode of DIHS 4 years previously, in which human
      herpesvirus-6 and Epstein-Barr virus (EBV) were reactivated. Expression of EBV
      encoded RNA was detected in the lymph node. On the basis of findings in this
      patient, we suggest that EBV is pathogenically important in the sequence of
      events leading to the onset of systemic lupus erythematosus and that patients
      with a history of DIHS may be at a risk of eventually developing autoimmune
      diseases.

PMID- 19088464
TI  - Accuracy of transcutaneous carbon dioxide tension measurements during
      cardiopulmonary exercise testing.
AB  - BACKGROUND: Measurements of transcutaneous carbon dioxide tension (PtcCO(2)) with
      current devices are proven to provide clinically acceptable agreement with
      measurements of partial arterial carbon dioxide tension (PaCO(2)) in several
      settings but not during cardiopulmonary exercise testing (CPET). OBJECTIVES: The
      primary objective of this study was to investigate the agreement between PaCO(2)
      and PtcCO(2) measurements (using a Tosca 500 with a Tosca sensor 92) during CPET.
      A secondary objective was to investigate the agreement between arterial and
      transcutaneous oxygen saturation (SaO(2), SpO(2)) as measured with this sensor
      during CPET. METHODS: In patients with various pulmonary diseases, PtcCO(2) and
      SpO(2) were continuously measured and compared with arterial blood gas samples
      during CPET. A maximum bias of 0.5 kPa and 95% limits of agreement (LOA) of 1 kPa
      between carbon dioxide pressure (PCO(2)) measurements were determined as
      clinically acceptable. RESULTS: In total 101 'paired' arterial and transcutaneous
      measurements were obtained from 21 patients. Bias between PaCO(2) and PtcCO(2)
      was -0.03 kPa with LOA from -0.78 to 0.71 kPa. Bias between SaO(2) and SpO(2) was
      -1.0% with LOA from -2.83 to 0.83%. CONCLUSIONS: Transcutaneous estimations of
      PCO(2) and SpO(2) are accurate and can be used in CPET, circumvening the need for
      arterial cannulation.

PMID- 19088465
TI  - New components of 'basal laminar deposits' in age-related macular degeneration.
AB  - Two new components of basal laminar deposit (BlamD) occurring in samples of
      submacular neovascular membranes surgically removed from patients with a wet
      (exudative) form of age-related macular degeneration are described. They are: (1)
      minute ribbon-like structures which occur singly and/or in a bunch and extend
      from the inner surface of the BlamD layer into the extracellular matrix (ECM)
      beneath the retinal pigment epithelium (RPE). The ribbons are composed of
      polarized molecules, aggregating in parallel, aligned transversally in register,
      morphologically similar to isolated collagen molecules of the short-chain type.
      Deeper in the BlamD but always close to its inner surface, aspects suggesting a
      transition between ribbons and (2) long-spacing collagen (LSC)-like aggregates
      characterized by periods bordered by a single dense band were observed. This band
      could arise from the globular domains of the polarized monomers, which assemble
      in parallel and display all their terminal extensions at the same end of each
      period resulting in the single dense band. The presence of ribbons and of LSC
      like aggregates in the BlamD layer and the concomitant choroidal
      neovascularization (CNV) suggest that the events might be correlated. The newly
      formed vessels crossing Bruch's membrane and invading the BlamD layer could
      induce physicochemical changes in the ECM of the RPE, providing the required
      environmental conditions for the polymerization of collagen molecules into
      aggregates with the LSC-like pattern. With the deposition of new components, the
      thickness of BlamD increases and further impairs the supply of nutrients and
      oxygen, thus sustaining CNV.

PMID- 19088466
TI  - Osteogenic and adipogenic cell fractions isolated from postnatal mouse calvaria.
AB  - The use of stem/progenitor cells represents a promising approach to treat
      craniofacial bone defects, but successful treatments will rely on the
      availability of cells that can be expanded in vitro and which will differentiate
      appropriately in vivo. The calvaria may represent a source of autologous cells
      for such purposes. We demonstrate expression of stem cell antigen-1 (Sca-1) in
      mouse calvaria. We isolated Sca-1(+) and Sca-1(-) cells at high purity and tested
      the ability of these cells to differentiate into adipose and bone. We show that
      the Sca-1(+) cell fraction has adipogenic differentiation potential and that the
      cell Sca-1(-) fraction has osteogenic differentiation potential. The Sca-1(+)
      cell fraction partially retains its adipogenic differentiation potential and the
      Sca-1(-) cell fraction partially retains its osteogenic differentiation potential
      after in vitro expansion. These data suggest that the calvaria may be used as a
      source of stem/progenitor cells that can be expanded in vitro and transplanted in
      vivo for craniofacial tissue regeneration.

PMID- 19088467
TI  - Route of epoetin administration influences hemoglobin variability in hemodialysis
      patients.
AB  - BACKGROUND: Compared to the intravenous route, subcutaneous administration of
      epoetin requires lower dose and will be an attractive option for cost containment
      when bundling for dialysis is implemented. Hemoglobin variability defined as
      fluctuation of hemoglobin over time has not been well studied with respect to the
      route of administration. METHODS: 157 prevalent-hemodialysis subjects were
      analyzed from an open-label, randomized study that compared the intravenous to
      the subcutaneous route of epoetin with identical weight-based dosing algorithm.
      Hemoglobin variability was defined as the number of weeks hemoglobin is outside
      the target range of 10-11 g/dl. Sensitivity analysis was performed. RESULTS: 78
      subjects in the intravenous and 79 in the subcutaneous group entered the 24-week
      dose maintenance phase. Baseline covariates were similar in both groups except
      for the dose of epoetin (lower in subcutaneous) and dialysis vintage (longer in
      intravenous). Patients on subcutaneous epoetin were outside the target range more
      weeks (p = 0.04) and had higher standard deviation of hemoglobin (p = 0.01)
      compared to the intravenous group. CONCLUSIONS: The subcutaneous route of epoetin
      was associated with modestly higher hemoglobin variability, probably reflecting
      greater sensitivity of the subcutaneous route and/or identical epoetin-dosing
      algorithm employed in both the arms. This study could serve as an important guide
      when bundling for dialysis services is implemented as switching from intravenous
      to subcutaneous administration is likely to occur.

PMID- 19088468
TI  - Clinical results and nutritional consequences of biliopancreatic diversion: three
      years of follow-up.
AB  - BACKGROUND: Bariatric surgery is the most effective long-term treatment for
      morbid obesity, reducing obesity-associated comorbidities. The aim of our work
      was to describe clinical results and nutritional complications in morbidly obese
      patients with biliopancreatic diversion. METHODS: We have analyzed a consecutive
      series of 64 patients who have been followed up for 3 years after undergoing open
      biliopancreatic diversion by the Scopinaro technique. RESULTS: Initial excess
      weight loss was 29.3% at 6 months and 61.5% at 3 years. A significant improvement
      of body mass index, weight, waist circumference, fat mass, glucose level, total
      cholesterol, uric acid and triglycerides levels was detected. Ferritin, vitamin
      A, vitamin D, vitamin B(12), zinc and copper levels showed a low percentage of
      deficiency at basal time, but during the follow-up, the percentage of deficiency
      increased. Vitamin E and K did not show basal deficiency. However, after surgery,
      a moderate deficiency of both vitamins was detected (vitamin E 7.1% and vitamin K
      8.3%). Folic acid deficiency was observed in 54.3% of the subjects at basal time,
      but decreased during the study. CONCLUSION: Biliopancreatic diversion is an
      effective method of sustainable weight loss. However, micronutrient deficiencies
      can occur.

PMID- 19088469
TI  - Urinary D-lactate excretion in infants receiving Lactobacillus johnsonii with
      formula.
AB  - BACKGROUND/AIMS: Supplementation with certain probiotics can improve gut
      microbial flora and immune function but should not have adverse effects. This
      study aimed to assess the risk of D-lactate accumulation and subsequent metabolic
      acidosis in infants fed on formula containing Lactobacillus johnsonii (La1).
      METHODS: In the framework of a double-blind, randomized controlled trial
      enrolling 71 infants aged 4-5 months, morning urine samples were collected before
      and 4 weeks after being fed formulas with or without La1 (1 x 10(8)/g powder) or
      being breastfed. Urinary D- and L-lactate concentrations were assayed by
      enzymatic, fluorimetric methods and excretion was normalized per mol creatinine.
      RESULTS: At baseline, no significant differences in urinary D-/L-lactate
      excretion among the formula-fed and breastfed groups were found. After 4 weeks, D
      lactate excretion did not differ between the two formula groups, but was higher
      in both formula groups than in breastfed infants. In all infants receiving La1,
      urinary D-lactate concentrations remained within the concentration ranges of age
      matched healthy infants which had been determined in an earlier study using the
      same analytical method. Urinary L-lactate also did not vary over time or among
      groups. CONCLUSIONS: Supplementation of La1 to formula did not affect urinary
      lactate excretion and there is no evidence of an increased risk of lactic
      acidosis.

PMID- 19088470
TI  - Developmental species differences in brain cell cycle rates between northern
      bobwhite quail (Colinus virginianus) and parakeets (Melopsittacus undulatus):
      implications for mosaic brain evolution.
AB  - Adult brains differ among species in the proportional sizes of their major
      subdivisions. For example, the telencephalon occupies 71% of the entire brain in
      parakeets (Melopsittacus undulatus) but only 54% in quail (Colinus virginianus).
      In contrast, the tectum is smaller in parakeets than in quail. To determine
      whether these differences in brain region size arise because of species
      differences in cell cycle rates, parakeet and quail embryos were collected at
      various stages of development (HH24-HH37) and stained with antibodies against
      proliferating cell nuclear antigen (PCNA), which labels all dividing cells, and
      phosphorylated histone-3 (pH3), which labels M-phase cells. Analysis of pH3+ cell
      densities and pH3+/PCNA+ cell ratios were used to compare cell cycle rates across
      stages and species. Cumulative labeling with bromodeoxyuridine (BrdU) was also
      used to compare cell cycle rates at stages 24 and 28 in quail. We found that
      telencephalic cell cycle rates lengthen with age in both species, but that they
      lengthen significantly later in parakeets than in quail. This species difference
      in cell cycle rates explains, at least partly, why adult parakeets have a
      proportionately larger telencephalon. Tectal cell cycle rates also remain
      elevated for a prolonged period of time in parakeets compared to quail. This
      seems paradoxical at first, given that the parakeet's adult tectum is relatively
      small. However, the tectum is initially much smaller but then grows more
      extensively in parakeets than in quail. Thus, species differences in adult brain
      proportions can be traced back to species differences in cell cycle kinetics.

PMID- 19088471
TI  - Diabetes as a risk factor for cognitive decline in older patients.
AB  - AIMS: To assess the role of type 2 diabetes as a risk factor for cognitive
      decline among elderly people. METHODS: Analyses were carried out on data from the
      Italian Longitudinal Study on Aging, a study on 5,632 subjects aged 65-84 years,
      with baseline in 1992 and follow-ups in 1996 and 2000. RESULTS: At baseline,
      diabetic women had significantly worse scores on all cognitive tests compared to
      nondiabetic women, but did not show worsening over time, whereas men with
      diabetes did not show worse scores on cognitive tests at baseline compared to
      nondiabetic males; however, diabetes in men was associated with a risk of
      cognitive decline over time, particularly in attention. Higher levels of HbA(1c)
      were associated with poorer performance on memory tests at follow-up in both
      sexes. CONCLUSION: The impact of diabetes on cognitive status might differ in
      older men and women, probably because of a survival effect, with a higher
      mortality at a younger age among diabetic men. The metabolic and cardiovascular
      abnormalities associated with diabetes might be responsible for the cognitive
      decline, at different rates and ages, in men and women. The routine assessment of
      diabetes complications in the elderly should include cognitive evaluation in both
      sexes.

PMID- 19088472
TI  - Functional magnetic resonance imaging of compensatory neural recruitment in aging
      and risk for Alzheimer's disease: review and recommendations.
AB  - There has been a recent proliferation of functional magnetic resonance imaging
      (fMRI) studies that interpret between-group or within-group differences in brain
      response patterns as evidence for compensatory neural recruitment. However, it is
      currently a challenge to determine whether these observed differences are truly
      attributable to compensatory neural recruitment or whether they are indicative of
      some other cognitive or physiological process. Therefore, the need for a
      standardized set of criteria for interpreting whether differences in brain
      response patterns are compensatory in nature is great. Focusing on studies of
      aging and potentially prodromal Alzheimer's disease conditions (genetic risk,
      mild cognitive impairment), we critically review the functional neuroimaging
      literature purporting evidence for compensatory neural recruitment. Finally, we
      end with a comprehensive model set of criteria for ascertaining the degree to
      which a 'compensatory' interpretation may be supported. This proposed model
      addresses significant brain region, activation pattern, and behavioral
      performance considerations, and is therefore termed the Region-Activation
      Performance model (RAP model).

PMID- 19088474
TI  - Associations between patterns of EEG abnormalities and diagnosis in a large
      memory clinic cohort.
AB  - AIM: To describe associations of abnormalities in the electroencephalogram (EEG)
      with the most prevalent diagnoses in a memory clinic cohort. METHODS:
      Associations between visual EEG findings and diagnoses in 1,116 consecutive
      patients [382 Alzheimer's disease (AD), 274 subjective complaints, 190 mild
      cognitive impairment (MCI), 118 psychiatric disorder, 61 frontotemporal lobar
      degeneration, 53 vascular dementia (VaD), 38 dementia with Lewy bodies (DLB)]
      were determined by prevalence ratio (PR). RESULTS: Diagnoses of subjective
      complaints [PR = 1.6; 95% confidence interval (CI) = 1.4-1.9] and psychiatric
      disorder (1.4; 95% CI = 1.1-1.9) were associated with a normal EEG, while
      subjects with both focal and diffuse EEG disturbances were more likely to have
      DLB (3.5; 95% CI = 2.1-5.6), VaD (2.3; 95% CI = 1.4-3.6) or AD (1.5; 95% CI = 1.3
      1.8). Subjects with only diffuse EEG abnormalities were more likely to have AD
      (PR = 1.5; 95% CI = 1.3-1.9). The prevalence of MCI was higher among those with
      only focal EEG abnormalities (PR = 1.3; 95% CI = 1.0-1.7). CONCLUSIONS: A normal
      EEG argues for subjective complaints or psychiatric diagnosis. An EEG with only
      focal abnormalities supports MCI. An EEG with only diffuse abnormalities argues
      for AD. An EEG with both focal and diffuse abnormalities argues for DLB, VaD or
      AD.

PMID- 19088473
TI  - Plasma homocysteine and risk of mild cognitive impairment.
AB  - BACKGROUND AND OBJECTIVE: There are conflicting data relating homocysteine levels
      to the risk of Alzheimer's disease (AD). We sought to explore whether fasting
      plasma homocysteine is associated with the risk of mild cognitive impairment
      (MCI), an intermediate stage to dementia. METHODS: Fasting levels of plasma
      homocysteine were obtained from 678 elderly subjects chosen at random from a
      cohort of Medicare recipients. There were longitudinal data in 516 subjects
      without MCI or dementia at baseline who were followed for 2,705 person-years. The
      relation of plasma homocysteine with prevalent and incident all-cause MCI,
      amnestic MCI and non-amnestic MCI was assessed using logistic and Cox
      proportional hazards regression analyses. RESULTS: There were 162 cases of
      prevalent MCI and 132 cases of incident MCI in 5.2 years of follow-up. There was
      no association between plasma homocysteine and prevalence of MCI or amnestic or
      non-amnestic MCI in the cross-sectional analyses. There was no association
      between higher homocysteine levels and a lower risk of all-cause MCI. Consistent
      with the cross-sectional analyses, there was no specific association with the
      amnestic or non-amnestic subtype of MCI in crude or adjusted models. CONCLUSION:
      Plasma homocysteine levels measured at baseline were not related to MCI or its
      subtypes in an elderly multiethnic cohort.

PMID- 19088475
TI  - Wound healing is not impaired in rats undergoing perioperative treatment with the
      antineoplastic agent taurolidine.
AB  - BACKGROUND/AIM: The aim of this study was to determine whether an intravenous or
      an intraperitoneal application of the antineoplastic agent taurolidine (TRD)
      impairs wound healing in the absence of tumor load in rats. METHODS: Eighty rats
      were randomized into eight groups (n = 10). Median laparotomy was performed in
      all animals. Three groups were treated by intravenous injection and three groups
      by local administration using a central port catheter system. For each group, 1
      ml was applied: isotone sodium chloride solution (control groups), 1% TRD, 2%
      TRD, and 3% TRD. Fascia and skin were closed using a standardized running suture
      technique with 4-0 Vicryl. Wounds were evaluated once a day. Animals were treated
      every 8 h for 7 days (ports were then removed) and wounds were evaluated at day
      28. Macroscopic and histopathologic examinations of scar tissue biopsies
      (hemalaun-eosin stain) were performed at the end of the experiment. RESULTS: No
      animal died. No relevant impairment of wound healing was observed independent of
      the different treatment strategies. CONCLUSION: Our results suggest that wound
      healing does not seem to be impaired by TRD in rats.

PMID- 19088476
TI  - Vascular anatomy of the hamster retractor muscle with regard to its microvascular
      transfer.
AB  - BACKGROUND: The hamster retractor muscle (RET) is used as an in vivo model in
      studies of skeletal muscle ischemia-reperfusion injury. The RET is unique in that
      the muscle can be isolated while preserving the primary vascular supply so that
      its contractile function can be measured simultaneously with local microvascular
      responses to experimental interventions. The goal of this study was to understand
      the anatomical origin of the vascular supply to the RET and determine whether the
      RET can be used as a free flap after surgical isolation of the thoracodorsal
      vessels. METHODS: Microdissection was performed to determine the anatomy of the
      vasculature that supplies and drains the RET. RESULTS: Distinct numbers and
      patterns of feed arteries (2-4) and collecting veins (1-3) were identified (n =
      26 animals). Dye injection (n = 8) of the thoracodorsal artery demonstrated that
      the RET remains perfused following its isolation on the thoracodorsal pedicle.
      Heterotopic allograft transplantation of the RET (n = 2) was performed by
      anastomosing the thoracodorsal vessels to the femoral vessels using the end-to
      side technique. CONCLUSIONS: The anatomical relationships indicate that the RET
      can be used as a free flap model for evaluating the effect of preservation
      strategies and transplantation on skeletal muscle microcirculation and
      contractile function.

PMID- 19088477
TI  - New practical course for laparoscopy training: anatomizing the orange.
AB  - PURPOSE: The aim of this study was to evaluate whether anatomizing the orange
      reliably improves laparoscopic skills and can therefore be used as a course in
      laparoscopic surgical training. MATERIALS AND METHODS: 12 trainees were required
      to practice baseline laparoscopic skills for 10 days and were then randomized
      into groups: 6 people who anatomized the orange for 1 h daily for 5 days and 6 in
      a control group who continued to practice the baseline laparoscopic skills. The
      trainees were tested on completing porcine laparoscopic nephrectomy. Operative
      performance was measured using a global assessment scale of surgical skill.
      RESULTS: The total score of global rating scale was 23.4 +/- 4.1 for the group
      who anatomized the orange and 18.3 +/- 2.7 for the control group (p < 0.05).
      Operative performance significantly improved in the group anatomizing the orange.
      CONCLUSION: Anatomizing the orange resulted in improving laparoscopic skills and
      can be incorporated into the laparoscopic training course. This could be
      beneficial for those who wish to develop the advanced skills required for various
      laparoscopic surgery procedures.

PMID- 19088479
TI  - Serum and tissue LDH levels in patients with breast/gynaecological cancer and
      benign diseases.
AB  - BACKGROUND: Lactate dehydrogenase A (LDHA) is involved in anaerobic glycolysis.
      In cancer patients, serum total lactate dehydrogenase (LDH) levels are often
      increased, and the gene for one of its isoenzymes, LDHA, is up-regulated. These
      features have been linked to poor prognosis in several studies. METHODS: We
      investigated comparatively the total serum LDH activity and tissue isoenzyme LDH5
      and hypoxia-inducible factor 1alpha (HIF1alpha) levels in patients with breast (n
      = 18) and gynaecological (n = 23) malignancies and benign diseases (n =54).
      RESULTS: The serum LDH levels were significantly higher in patients with
      endometrial adenocarcinoma (349 +/- 100 IU/l) and ovarian cystadenocarcinomas
      (383 +/- 116 IU/l) compared to healthy controls (256 +/- 68 IU/l) (p values 0.01
      and 0.006, respectively). This difference did not reach significance in patients
      with breast cancer (328 +/- 169 IU/l; p = 0.17)). Uterine leiomyoma patients
      showed intermediate LDH levels (310 +/- 81 IU/l), while patients with breast
      fibroadenomas and ovarian cystadenomas had LDH serum levels close to carcinomas
      (308 +/- 60 and 348 +/- 135 IU/l, respectively). LDH5 isoenzyme was strongly
      expressed in cancer cells, exhibiting a mixed cytoplasmic/nuclear subcellular
      pattern. Interestingly, a high LDH5 content in tissue sections was not invariably
      accompanied by high LDH serum levels. High HIF1alpha tissue expression was linked
      to high tissue LDH5 expression. CONCLUSION: Serum and tissue LDH is up-regulated
      in gynaecologic and breast malignancies and in a subset of benign conditions such
      as fibro- and cystadenomas. The release of LDH, however, in the bloodstream is
      partly related to the LDHA gene up-regulation.

PMID- 19088478
TI  - Analysis of diadochokinesis in ataxic dysarthria using the motor speech profile
      program.
AB  - AIMS: The Diadochokinetic Rate Analysis (DRA) in the KayPENTAX Motor Speech
      Profile is a computer program for the analysis of diadochokinesis (DDK). The
      objective of this study is to evaluate the suitability, reliability, and
      concurrent validity of the results from the DRA protocol and hand measurement for
      individuals with ataxic dysarthria, which is characteristically associated with
      dysdiadochokinesis. METHODS: Twenty-one participants with ataxic dysarthria were
      recorded as they repeated various syllables as quickly and steadily as possible.
      The DDK samples were executed by the DRA protocol at different thresholds and
      were also hand-measured. Analyses were based on the percentage of nonexecutable
      DDK samples, defined as samples in which the lowest peak intensity during CV
      syllables is lower than the highest peak intensity during intersyllable pauses,
      and the comparisons of the results between repeated analyses at different
      thresholds and between automatic and manual measuring methods. RESULTS: (1) More
      than one third of the DDK samples were nonexecutable; (2) the reliability at
      different thresholds and concurrent validity between different measuring methods
      were both satisfactory, and (3) temporal variation parameters were more
      inconsistent between different measuring methods than intensity variation
      parameters. CONCLUSION: DRA has notable limitations in its clinical application
      but there is a considerable potential for improving its performance.

PMID- 19088480
TI  - Patient satisfaction after laparoscopic total or supracervical hysterectomy.
AB  - BACKGROUND/AIMS: To evaluate patient satisfaction after laparoscopic
      supracervical (LASH) or total hysterectomy (TLH). METHODS: Retrospective study of
      patient satisfaction after LASH or TLH. RESULTS: We studied 40 cases of LASH and
      another 40 of TLH. The age of the patients, marital status, education level and
      employment status between the two groups were comparable. Both LASH and TLH
      results in improvement of general health and symptoms. However, there was no
      significant difference in patient satisfaction with surgery, in general health,
      body and self-images, and sexual satisfaction between the LASH and TLH group.
      Before surgery, patients in the TLH group experienced more pain with a sexual
      relationship than those in the LASH group. The difference became non-significant
      after surgery. There was no difference in urinary or gastrointestinal symptoms
      after either type of hysterectomy. CONCLUSIONS: Both LASH and TLH result in
      improvement of general health and symptoms. Body and self-images, sexual
      function, gastrointestinal and urinary functions after LASH or TLH are
      comparable.

PMID- 19088481
TI  - Positive adnexal or uterine serosal involvement in stage IIIC endometrial cancer
      is an adverse factor for recurrence.
AB  - OBJECTIVES: Clinical and pathological significance of stage IIIC endometrial
      cancer is unclear. Our study was designed to determine the risk of recurrence
      among patients with stage IIIC endometrial cancer according to different
      pathological findings. METHODS: We retrospectively reviewed all patients with
      FIGO IIIC endometrial carcinoma (n = 48) treated in our institution between 1996
      and 2005. Patients without comprehensive surgical staging were excluded. Patients
      were classified into two groups: with adnexae and/or uterine serosal metastasis
      (group A, n = 18) and without metastasis (group B, n = 20). Cox proportional
      hazards model was used for multiple regression analysis. RESULTS: Mean age was 64
      years (range 46-90). Eighteen patients received adjuvant chemotherapy and pelvic
      radiotherapy, 17 received pelvic radiotherapy alone, and 11 received chemotherapy
      or hormonotherapy. At a median follow-up of 26.7 months, 12 had recurrence of the
      disease. Serosal and/or adnexal involvement was a negative independent prognostic
      factor for disease-free survival [relative risk = 3.75 (1.01-13.9); p = 0.04],
      whereas histological type, grade, depth of invasion and age at diagnosis had no
      influence. CONCLUSION: Patients with stage IIIC endometrial cancer and metastasis
      to adnexae and/or serosa have a higher risk of recurrence than those with node
      metastasis alone. Optimal adjuvant therapy for these groups remains unclear.

PMID- 19088482
TI  - Understanding symptoms in patients with advanced chronic kidney disease managed
      without dialysis: use of a short patient-completed assessment tool.
AB  - BACKGROUND: It is often believed that patients with advanced chronic kidney
      disease (CKD) stage 4-5 have few symptoms, and that dying with renal disease is
      relatively symptom-free. But the symptom burden of patients managed
      conservatively (without dialysis), with potentially high levels of comorbidity
      and poor functional status, is unknown. This clinical audit evaluated the
      prevalence and severity of symptoms in conservatively managed CKD stage 4-5
      patients. METHODS: Symptom data was collected from all conservatively managed
      patients from 2 renal units referred to a new renal palliative care service over
      a 10-month period between April 2005 and January 2006. Data on symptom prevalence
      and severity was collected as part of their routine clinical care, using a
      modified version of the Patient Outcome Scale--symptom module (POSs). This
      patient-completed instrument identifies the presence and severity of 17 symptoms.
      Demographic data was also collected, including estimated glomerular filtration
      rate (eGFR) using the MDRD formula, primary renal diagnosis and comorbidity.
      RESULTS: Symptoms were evaluated in 55 patients, with a mean age of 82 years (SD
      5.5, range 66-96). eGFR ranged from 3 to 30 ml/min (median 11, mean 12.75). In
      patients with CKD stage 4-5, managed without dialysis, the symptom burden is
      high. The most prevalent symptoms reported were weakness (75%), poor mobility
      (75%), poor appetite (58%), pain (56%), pruritus (56%) and dyspnoea (49%). The
      total number of symptoms each individual patient experienced ranged from 1 to 14
      (median 7, mean 6.8). Symptoms were frequently reported as moderate, severe, or
      overwhelming; in 54% of patients with poor mobility, 48% with weakness, 30% with
      itching, 31% with anorexia and 27% with pain. No significant association was
      demonstrated between the number of symptoms experienced and either severity of
      renal disease or comorbidity score. CONCLUSIONS: This structured clinical
      evaluation demonstrates the extent and severity of symptom burden in
      conservatively managed patients with CKD stage 4-5, and demonstrates the use of
      an appropriate clinical tool that can be used to assess the efficacy of
      treatment.

PMID- 19088483
TI  - Switching from epoetin alpha to darbepoetin alpha in Japanese hemodialysis
      patients: dose conversion ratio.
AB  - BACKGROUND/AIMS: Darbepoetin alpha is an erythropoietic agent with a 3-fold
      longer elimination half-life than epoetin. The recommended conversion ratio from
      epoetin to darbepoetin alpha is 1:200 (1 microg of darbepoetin alpha = 200 IU of
      epoetin), but several observations have suggested that this ratio overestimates
      the required dose of darbepoetin alpha. This study assessed the actual conversion
      ratio for stable Japanese hemodialysis patients and investigated whether
      darbepoetin alpha promotes uniform erythropoiesis. METHODS: A total of 104
      hemodialysis patients who were stable on epoetin alpha therapy at Hakuai Clinic
      in Japan were switched to intravenous darbepoetin alpha according to the 1:200
      rule. They were followed for 24 weeks to assess changes of hemoglobin and the
      dose of darbepoetin alpha, as well as changes of the reticulocyte count. RESULTS:
      One hundred patients completed the 24-week study and the final conversion ratio
      was 1:350.5. Darbepoetin alpha showed a similar effect in diabetics and
      nondiabetics. Data on the reticulocyte count demonstrated that darbepoetin alpha
      had a sustained effect on erythropoiesis. CONCLUSION: Darbepoetin alpha is
      effective for Japanese dialysis patients at a lower dose than expected.

PMID- 19088484
TI  - A population-based study of the association between Trypanosoma cruzi infection
      and cognitive impairment in old age (the Bambui Study).
AB  - BACKGROUND: Limited clinical data suggest that chronic Trypanosoma cruzi
      infection, which causes Chagas' disease (ChD), is associated with cognitive
      impairment. This study investigated this association in a large population-based
      sample of older adults. METHODS: Participants in this cross-sectional study
      comprised 1,449 persons aged > or = 60 years from a Brazilian endemic area
      (Bambui). Cognitive functioning was ascertained by the Mini-Mental State
      Examination (MMSE), considering its score in percentiles [< or =14 (<5th
      percentile), 15-22 (5th to <25th) and > or =23]. Hypothesized risk factors were
      T. cruzi infection, ChD-related electrocardiographic (ECG) abnormalities and use
      of digoxin medication. Potential confounders included depressive symptoms,
      smoking, stroke, hemoglobin, HDL cholesterol, blood glucose, systolic blood
      pressure, and use of psychoactive medication. RESULTS: The prevalence of T. cruzi
      infection was 37.6%. There was a graded and independent association between
      infection and the MMSE score (adjusted odds ratios estimated by ordinal logistic
      regression = 1.99; 95% CI 1.43-2.76). No significant associations between the
      MMSE score and ECG abnormalities or digoxin medication use were found.
      CONCLUSIONS: This study provides for the first time epidemiological evidence of
      an association between T. cruzi infection and cognitive impairment which was not
      mediated by either ChD-related ECG abnormalities or digoxin medication use.

PMID- 19088485
TI  - Epidemiological survey of epilepsy in the special school population in the city
      of Buenos Aires. A comparison with mainstream schools.
AB  - BACKGROUND: Previous studies in special schools have shown a high prevalence of
      epilepsy, which is strongly associated with cerebral palsy and severe mental
      retardation. The conditions regulating school placement have also been described
      in those studies. In the City of Buenos Aires, information is known only for
      mainstream schools. OBJECTIVE: To determine the prevalence and characteristics of
      epilepsy in special schools and to compare results with common primary education
      settings. DESIGN AND METHODS: A cross-sectional study was carried out in special
      schools in the City of Buenos Aires, by adopting the same definitions, diagnostic
      criteria and questionnaire as those used in a previous study in the common
      primary school population. Responses from 1,682 children, aged 6-16 years,
      residing in the City of Buenos Aires, with mental retardation, visual or hearing
      impairment, psychiatric disorders and motor disabilities were analyzed. RESULTS:
      A total of 121 children with epilepsy were detected. Lifetime prevalence was 71.9
      per thousand and active prevalence was 64.8 per thousand (22-25 times greater
      than rates in mainstream schools). Prevalence was highest in girls and
      generalized seizures prevailed over other seizure types. Ninety-two percent of
      cases received antiepileptic drugs, 57.9% as a single drug treatment and 85.1% in
      adequate doses. Only 56% of the children with a diagnosis of epilepsy proved to
      be true-positive cases, and almost 40% received antiepileptic drugs for
      nonepileptic disorders. Malformations/degenerative disease were the most common
      etiology. CONCLUSIONS: Special schools contain clusters of children with epilepsy
      as a comorbid condition. False high frequency is due to misdiagnoses and
      unnecessary treatments. These schools are an important target for educational
      interventions.

PMID- 19088486
TI  - Clinicoepidemiological profiles and outcomes during first hospital admission of
      head injury patients in Ikeja, Nigeria. A prospective cohort study.
AB  - BACKGROUND: Although head injury (HI) is a major public health problem in Nigeria
      and other low and middle income countries of the world, there is a paucity of
      data from these societies. This is largely due to under-reporting. We carried out
      a prospective study of the clinicoepidemiological profiles and outcomes following
      the first hospitalization of a cohort of head-injured patients in Ikeja, Nigeria,
      a metropolitan African city. METHODS: In an 8-month period from May until
      December 2005, data from all HI cases seen in our neurosurgical unit were
      prospectively recorded for subsequent analysis. These include demographics,
      mechanism of injury, pre-neurosurgical care received, severity of injury using
      the Glasgow Coma Scale, presence of hemodynamic instability, pupillary anomalies
      and associated systemic injuries, cranial computed tomography (CT) findings and
      the number of surgical interventions, as well as outcomes after the first
      hospital admission using the Glasgow Outcome Scale. Determinants of outcome were
      explored using the chi(2) test and the level of significance was put at p = 0.05.
      RESULTS: There were 143 cases of HI, which is about one fifth of our total
      workload, including 122 males and 21 females aged 0.5-85 years (mean age 29.15).
      The majority (88%) were either school children or low income earners. Road
      accidents accounted for 75% of the cases; three quarter of the cases had some
      initial care in other health facilities before the arrival in our unit, at an
      average of 33 h. Mild, moderate and severe HI accounted for 60, 18 and 22%,
      respectively. About a quarter of the patients sustained other systemic injuries.
      Cranial CT scanning was obtainable in 40 patients (28%); 9 of these revealed
      surgical mass lesions, of whom 5 had life-saving operations. Many well-known
      determinants of a poor outcome of HI were prevalent in this study group and found
      to have a significantly adverse effect on patient outcome. CONCLUSIONS: HI is a
      major public health problem in Nigeria, taking up at least one fifth of the
      neurosurgical workload. The prehospital emergency medical service is poorly
      organized. Determinants of a poor outcome of HI are highly prevalent, including
      poor accessibility to cranial CT scanning, absence or inadequacy of logistics for
      neurocritical care and an inadequate number of neurosurgeons.

PMID- 19088487
TI  - Acute treatment costs of stroke in Brazil.
AB  - BACKGROUND AND PURPOSE: Although stroke is the leading cause of death in Brazil,
      little information exist on the acute treatment provided for stroke and its
      associated costs. This study addresses this gap by both clinically and
      economically characterizing the acute treatment of first-ever intracerebral
      hemorrhage (ICH) and ischemic stroke (IS) in Brazil. METHODS: Retrospective
      medical chart review using data from two high-volume stroke centers in Sao Paulo,
      Brazil. Clinical and resource utilization data for all patients admitted to the
      stroke centers with a first-ever stroke between January 1, 2006 and May 31, 2007
      were collected and the mean acute treatment costs per person were calculated by
      assigning appropriate unit cost data to all resource use. Cost estimates in
      Brazilian reals (BRL) were converted to US dollars (USD) using the 2005
      purchasing power parity index. National costs of acute treatment for incident
      strokes were estimated by extrapolation of mean cost estimate per person to
      national incidence data for the two types of stroke. The mean costs of acute
      treatment on a national scale were examined in sensitivity analysis. RESULTS: A
      total of 316 stroke patients were identified and their demographic and clinical
      characteristics, patterns of care, and outcomes were examined. Mean length of
      hospital stay was 12.0 +/- 8.8 days for ICH and 13.3 +/-23.4 days for IS. Ninety
      one percent of the ICH patients and 68% of the IS patients were admitted to an
      intensive care unit (ICU). Mean total costs of initial hospitalization were USD
      4,101 (SD +/-4,254) for ICH and USD 1,902 (SD +/-1,426) for IS. In multivariate
      analysis, hemorrhagic stroke, development of pneumonia, neurosurgical
      intervention, stay in ICU, and physical therapy were all significant independent
      predictors of acute treatment costs. Aggregate national health care expenditures
      for acute treatment of incident ICH were USD 122.4 million (range 30.8-274.2) and
      USD 326.9 million for IS (range 82.4-732.2). CONCLUSION: Acute treatment costs of
      incident ICH and IS in Brazil are substantial and primarily driven by the
      intensity of hospital treatment and in-hospital complications. With the expected
      increase in the incidence of stroke in Brazil over the coming decades, these
      results emphasize the need for effective preventive and acute medical care.

PMID- 19088488
TI  - The epidemiology of Guillain-Barre syndrome worldwide. A systematic literature
      review.
AB  - BACKGROUND: This systematic literature review of the epidemiology of Guillain
      Barre syndrome (GBS) identifies trends in incidence rates by age, study method
      and cause of disease. It is important to have a reliable estimate of incidence to
      determine and investigate any changes: no previous systematic reviews of GBS have
      been found. METHODS: After critical assessment of the reliability of the reported
      data, incidence rates were extracted from all relevant papers published between
      1980 and 2008, identified through searches of Medline, Embase and Science Direct.
      RESULTS: Sixty-three papers were included in this review; these studies were
      prospective, retrospective reviews of medical records or retrospective database
      studies. Ten studies reported on the incidence in children (0-15 years old), and
      found the annual incidence to be between 0.34 and 1.34/100,000. Most studies
      investigated populations in Europe and North America and reported similar annual
      incidence rates, i.e. between 0.84 and 1.91/100,000. A decrease in incidence over
      the time between the 1980s and 1990s was found. Up to 70% of cases of GBS were
      caused by antecedent infections. CONCLUSIONS: Our best estimate of the overall
      incidence of GBS was between 1.1/100,000/year and 1.8/100,000/year. The incidence
      of GBS increased with age after 50 years from 1.7/100,000/year to
      3.3/100,000/year.

PMID- 19088489
TI  - A medical enigma: persons with Down syndrome do not develop medulloblastoma.

PMID- 19088490
TI  - Cognitive performance and grey matter density in psychosis: functional relevance
      of a structural endophenotype.
AB  - BACKGROUND: Structural brain changes and cognitive impairments have been
      identified as indicators of genetic risk for schizophrenia. However, the pattern
      of associations between such structural and functional liability markers has been
      less well investigated. METHODS: Magnetic resonance imaging data and cognitive
      assessments were acquired in 31 patients with psychosis, 32 non-psychotic first
      degree relatives and 28 controls. The relationship between cerebral grey matter
      density and cognitive performance was examined using computational morphometry.
      RESULTS: Two out of 6 cognitive tests revealed significant associations with grey
      matter density in regions of the frontal lobe, basal ganglia, thalamus and
      cerebellum in patients and relatives. In patients, poorer executive functioning
      was associated with cerebellar grey matter density deficits. In relatives, poorer
      executive functioning was associated with increased grey matter density in the
      cerebellum and frontal lobe. In both patients and relatives, strategic retrieval
      from semantic memory was positively associated with grey matter density in basal
      ganglia structures. Some additional negative associations in the patients
      differentiated this group from relatives. CONCLUSIONS: The overlap in structure
      function relationships in individuals with schizophrenia and those with liability
      for the disorder may suggest that regional grey matter density alterations
      functionally alter particular neurocircuits, which could lead to cognitive
      deficits. The non-overlapping structure-function correlations may reflect disease
      related or compensatory mechanisms.

PMID- 19088491
TI  - Differential susceptibility to extinction-induced despair and age-dependent
      alterations in the hypothalamic-pituitary-adrenal axis and neurochemical
      parameters.
AB  - Clinical studies point to structural differences in the neurobiological
      mechanisms underlying early versus late onset of depression. However, studies
      examining the neuropathology of depressive-like behavior induced in the aged
      rodent are sparse. Extinction of learned behavior induces be- havioral 'despair',
      and is held to provide a conceptual and empirical model of human depression
      resulting from the withdrawal of reinforcement. We tested whether the
      neuroendocrinological and chemical concomitants of susceptibility to extinction
      induced despair in aged animals differed from adult ones. Following the
      withholding of reinforcement (extinction of escape from a water maze), a number
      of aged and adult rats are prone to develop depressive-like behavior, i.e.
      immobility. Analysis of hypothalamus-pituitary-adrenal (HPA) axis markers
      revealed an increase in the mineralocorticoid/glucocorticoid receptor (MR/GR)
      mRNA ratio in the CA1 region of the hippocampus in aged and adult despair
      animals; however, in dependence on age, divergent changes contributed to the
      enhanced ratio. While aged despair rats had less GR mRNA, adult despair rats had
      more MR mRNA. Furthermore, age- and despair-related interactions with hippocampal
      and cortical steroid receptor co-activators and neurotransmitter contents in
      diverse brain areas were found. For instance, adult despair rats had an
      increased, and aged despair rats a decreased, DOPAC/dopamine turnover compared to
      the respective non-despair group. These results show that neurobiological
      underpinnings of depression in the aged differ from those of adults, and
      underline the importance of investigating age-related alterations in HPA axis
      dynamics in conjunction with neurotransmitter systems to advance our knowledge
      about neuronal mechanisms of late-life and/or late-onset depression.

PMID- 19088492
TI  - Impact of gene-gender effects of adrenergic polymorphisms on hypothalamic
      pituitary-adrenal axis activity in depressed patients.
AB  - OBJECTIVE: There is overwhelming evidence that activation of the hypothalamic
      pituitary-adrenal (HPA) system plays a major role in depression and
      cardiovascular disease in genetically susceptible individuals. We hypothesized
      that due to the multiple interactions between the sympathetic and the HPA systems
      via adrenoceptors, polymorphisms in these genes could have an impact on HPA axis
      activity in major depression. METHODS: Using the dexamethasone/corticotrophin
      releasing hormone (DEX/CRH) test, we investigated the association of alpha(2)
      adrenoceptor (ADRA2A -1291C-->G) and the beta(2)-adrenoceptor gene (ADRB2
      Arg16Gly) in 189 patients with major depression during the acute state of the
      disease and after remission. RESULTS: Male ADRA2A -1291G allele homozygotes
      showed significant pretreatment HPA axis hyperactivity, with increased
      adrenocorticotropin (ACTH; F = 4.9, d.f. = 2, p = 0.009) and cortisol responses
      (F = 6.4, d.f. = 2, p = 0.003). In contrast, female ADRB2 Arg/Arg homozygotes had
      increased pretreatment ACTH (F = 7.17, d.f. = 2, p = 0.001) and cortisol (F =
      8.95, d.f. = 2, p = 0.000) levels. Interestingly, in the respective genotypes,
      the stress hormones remained elevated in the second DEX/CRH test, despite a
      reduction in depressive symptoms. CONCLUSIONS: This study provides evidence that,
      depending on gender and polymorphisms, there is continuous HPA axis overdrive in
      a proportion of patients irrespective of the status of depression. Considering
      the importance of stress hormones for cardiovascular disorders, our data might
      suggest that these patients are at high risk of comorbidity between depression
      and cardiovascular disorders.

PMID- 19088493
TI  - Meta-analysis of the brain-derived neurotrophic factor gene (BDNF) Val66Met
      polymorphism in anxiety disorders and anxiety-related personality traits.
AB  - OBJECTIVE: Brain-derived neurotrophic factor (BDNF) is potentially involved in
      the pathogenesis of anxiety. We carried out meta-analyses to evaluate the
      relationship between the BDNF Val66Met (valine, methionine) polymorphism and
      anxiety disorders (AD) or anxiety-related personality traits (ARPT). METHODS:
      Medline, Embase and PsycINFO were searched up to December 2007. We investigated 3
      outcomes related to BDNF Val66Met polymorphisms: (1) clinically diagnosed cases
      of AD; (2) ARPT in subjects without psychiatric diagnoses, assessed either by the
      Neuroticism scale of NEO-Personality Inventory forms (NEO-PI, NEO-PI-R, NEO-FFI),
      or by (3) the Harm Avoidance (HA) scale of Tridimensional Personality
      Questionnaire (TPQ) or its extended version Temperament and Character Inventory
      (TCI). RESULTS: Seven case-control studies were selected for AD, including 1,092
      cases and 8,394 controls, while 5 cross-sectional studies for Neuroticism (n =
      1,633) and 4 for HA (n = 607). Both Met/Met and Val/Met individuals, as compared
      to Val/Val, showed a statistically significant lower Neuroticism score [SMD = 
      0.24 (95% CI: -0.44, -0.04), and -0.11 (95% CI: -0.22, -0.01), respectively]. No
      significant association was found between BDNF Val66Met polymorphism and AD [OR =
      1.13 (95% CI: 0.85-1.52) for Met/Met versus Val/Val] or HA [SMD = 0.11 (95% CI: 
      0.19, 0.42) for Met/Met vs. Val/Val]. CONCLUSIONS: The low number of studies on
      this topic and their limited sample size, along with the inner limits in the
      definition of anxiety phenotypes, suggest caution in the interpretation of these
      results. Larger additional studies possibly investigating the interaction with
      other genes and environmental exposures are required to confirm these results.

PMID- 19088494
TI  - Early intravitreal bevacizumab for non-ischaemic branch retinal vein occlusion.
AB  - PURPOSE: To evaluate the effect of early intravitreal bevacizumab application in
      patients with macular oedema due to non-ischaemic branch retinal vein occlusion
      (BRVO). PROCEDURES: The study included 21 patients (21 eyes) with macular oedema
      due to non-ischaemic BRVO. Inclusion criteria were significant macular oedema as
      measured by optical coherence tomography, loss of visual acuity and leakage in
      fluorescence angiography. All patients received 3 intravitreal injections of 1.5
      mg bevacizumab. The mean follow-up was 6.2 +/- 1.2 months (mean +/- standard
      deviation). The mean duration of the BRVO prior to treatment was 9.2 +/- 5.4
      days. RESULTS: The visual acuity improved significantly from baseline 0.81 +/-
      0.53 logMAR to 0.54 +/- 0.47 logMAR (p < 0.001) at 1 month, 0.55 +/- 0.46 (p =
      0.001) at 3 months and to 0.55 +/- 0.49 (p = 0.002) at 6 months after the first
      injection. The mean central retinal thickness decreased significantly (p < 0.001)
      from 492 +/- 113 microm at baseline to 294 +/- 117 microm at 1 month after the
      first injection to 325 +/- 127 microm at 3 months (p < 0.001) and to 316 +/- 117
      microm at 6 months (p < 0.001) after the first injection. The increase in visual
      acuity correlated significantly (p < 0.01) with the decrease in macular
      thickness. CONCLUSIONS: Early intravitreal injection of bevacizumab may decrease
      macular oedema and improve visual acuity in eyes with non-ischaemic BRVO.

PMID- 19088495
TI  - Possibility of topical antioxidant treatment of cataracts: corneal penetration of
      pyruvate in humans.
AB  - AIM: It was our aim to study the penetration of sodium pyruvate into the aqueous
      humor of humans after its topical application as an eye drop. METHODS: Two hours
      prior to surgery, one drop of 5% sodium pyruvate prepared in artificial tears was
      instilled in the eye to be operated upon for cataract extraction. The drops were
      given 4 times at 10-min intervals. Eye drops containing tropicamide,
      phenylephrine, flurbiprofen and tobramycin were also given preoperatively. At the
      start of surgery, an aqueous sample was withdrawn, kept refrigerated and analyzed
      for pyruvate within 2 h. The cataracts were then extracted either by routine
      extracapsular extraction or by phacoemulsification, both followed by intraocular
      lens implantation. The pyruvate level was determined colorimetrically by reacting
      it with 2,4-dinitrophenyl hydrazine. RESULTS: The level of pyruvate in the
      aqueous sample of patients that did not receive pyruvate eye drops was only 0.145
      +/- 0.06 mM. In the group given pyruvate, it increased to approximately 0.35
      0.525 mM. CONCLUSION: The results demonstrate that topical administration of
      pyruvate is effective in elevating its concentration in the aqueous humor to a
      level adequate to offer protection against oxidative stress to the lens and other
      intraocular tissues. Hence, it should be feasible to carry out clinical trials
      with this compound aimed at treating diseases such as cataracts and diabetic
      retinopathy induced by generation of reactive oxygen species and consequent
      oxidative stress.

PMID- 19088496
TI  - Expression pattern of aquaporin 1 in the middle ear of the guinea pig with
      secretory otitis media.
AB  - OBJECTIVE: To explore the pathological change of water homeostasis in the
      secretory otitis media (SOM) middle ear, we observed the expression and
      regulation of aquaporin 1 (AQP1) in the SOM middle ear cavity. METHODS: Reverse
      transcriptase polymerase chain reaction (RT-PCR), Western blotting and
      immunohistochemical staining were used to detect AQP1 in the bullae of SOM models
      and normal animals. The expression patterns of AQP1 in the SOM group were
      compared with those in the normal animal group. RESULTS: RT-PCR and immunoblot
      analyses revealed that mRNAs encoding AQP1 were expressed in the middle ear
      membrane of the guinea pigs of both groups; AQP1 was also detected as 28-kDa
      proteins in both groups. Immunohistochemical analysis showed that AQP1 was
      localized on capillary endothelial cells and fibroblasts in the lamina propria
      mucosae as well as on flat and cubical epithelial cells. Quantitative analysis of
      RT-PCR and Western blotting revealed that AQP1 expression was higher in the SOM
      group than in the control group. The cellular expression of AQP1 was somewhat
      altered in the SOM middle ear. CONCLUSIONS: Our study suggests that AQP1 in the
      middle ear cavity may play a vital role in the accumulation of the effusion. It
      might work on the vessel-caused hydrops in the middle ear cavity.

PMID- 19088497
TI  - Preclinical toxicokinetic evaluation of phortress [2-(4-amino-3-methylphenyl)-5
      fluorobenzothiazole lysylamide dihydrochloride] in two rodent species.
AB  - BACKGROUND AND AIMS: The 2-(4-amino-3-methylphenyl)-5-fluorobenzothiazole prodrug
      Phortress exerts potent and selective antitumour activity in vitro and in vivo.
      Preclinical toxicokinetic studies in 2 rodent species were undertaken to
      determine Phortress' maximum tolerated dose and advise a safe starting dose for
      clinical evaluation. METHODS: Plasma pharmacokinetic parameters were determined
      by high-performance liquid chromatography and fluorescence detection following
      Phortress administration to mice (10 mg/kg, intravenously on days 1 and 8).
      Phortress (20 mg/kg, on days 1 and 8) was administered to CYP1A1/betaGAL reporter
      mice; tissues were examined macro- and microscopically. Toxicological and
      pharmacodynamic endpoints were examined in organs of rodents receiving Phortress
      (10 mg/kg or 20 mg/kg, on days 1 and 8). CYP1A1 expression and Phortress-derived
      DNA adducts were determined in lungs and livers (on days 11 and 36). RESULTS: No
      accumulation of Phortress was detected in murine plasma. beta-Galactosidase
      activity inferred Phortress-derived induction of cyp1a1 transcription in the
      livers of transgenic mice; no total body weight loss was encountered in these
      animals. However, a fall in lung:body weight and kidney:body weight ratios,
      raised serum alkaline phosphatase levels and hepatic histopathological
      disturbances in animals receiving 20 mg/kg Phortress indicate organ sites of
      potential toxicity. CYP1A1 protein was induced transiently in the lungs of both
      species and in the livers of rats. Elimination of hepatic DNA adducts and rat
      pulmonary adducts was evident; however, murine pulmonary adducts persisted.
      CONCLUSION: Rodent preclinical toxicology established that mice represent the
      more sensitive rodent species, resolving a maximum tolerated dose of 10 mg/kg
      Phortress.

PMID- 19088498
TI  - Influence of ethanol on the solubility, ionization and permeation characteristics
      of ibuprofen in silicone and human skin.
AB  - In the context of topical and transdermal delivery, cosolvents may be expected to
      enhance solubility, modify drug partitioning behaviour and alter skin barrier
      properties. In the present study, we have investigated systematically the
      influence of increasing amounts of the cosolvent ethanol on the solubility,
      ionization, and permeability characteristics of ibuprofen in silicone and in
      skin. The possibility of ibuprofen self-association was also examined. As the
      amount of ethanol was raised from 0 to 100%, ibuprofen solubility was enhanced
      5,500-fold relative to its aqueous solubility. Up to 50%, the pK(a) of ibuprofen
      shifted from 4.44 to 5.68. Infrared spectroscopy confirmed the presence of
      ibuprofen in both monomer and dimer forms in vehicles containing 75 and 100%
      ethanol. In silicone membranes, the flux of ibuprofen increased 8-fold over the
      range of ethanol concentrations studied (0-100%) relative to aqueous solutions,
      with the highest flux observed for 100% ethanol. However, in skin, the flux of
      ibuprofen was optimal for 50:50 and 75:25 ethanol-water vehicles (>10-fold flux
      enhancement). The lower ibuprofen flux from pure ethanol may reflect the
      alcohol's ability to dehydrate human skin. In general, the flux data confirm that
      increasing ethanol content enhances the solubility of ibuprofen in silicone and
      human skin as well as in the vehicle itself.

PMID- 19088499
TI  - Short-chain ceramides decrease skin barrier properties.
AB  - Stratum corneum ceramides are major determinants of skin barrier function.
      Although their physiological and pathological role has been widely investigated,
      to date no structure-activity relationships have been established. In this study,
      a series of short-chain ceramide analogues with polar head structure identical to
      ceramide NS, a sphingosine length of 12 carbons and an acyl chain length of 2-12
      carbons was synthesized. Their effect on skin permeability was evaluated using
      porcine skin and two model drugs, theophylline and indomethacin, and compared to
      that of a physiological ceramide NS. The results showed that the ceramide chain
      length was crucial for their barrier properties. Ceramides with a 4- to 8-carbon
      acyl chain were able to increase skin permeability for both drugs up to 10.8
      times with maximum effect at a 6-carbon acyl chain. No increase in permeability
      was found for ceramide analogues with 2- and 12-carbon acyl chains and ceramide
      NS. The same relationships were obtained for skin concentrations of the model
      drugs. The relationship between ceramide acyl chain length and its ability to
      perturb skin barrier showed striking similarity to the behavior of short-chain
      ceramides in sphingomyelin/phospholipid membranes and confirmed that short-chain
      ceramides do not act as natural ceramides and their use as experimental tools
      should be cautious.

PMID- 19088500
TI  - Downmodulatory effects of the antihistaminic drug bepotastine on
      cytokine/chemokine production and CD54 expression in human keratinocytes.
AB  - Bepotastine besilate is an antihistaminic drug of the second generation with
      superior clinical responses. In this study, we investigated whether bepotastine
      modulates the production of cytokines/chemokines and the expression of CD54 in
      human epidermal keratinocytes. The production of IL-1alpha, CXCL10, and CCL17 and
      the expression of CD54 were significantly suppressed by the addition of
      bepotastine. Bepotastine exerts its antiallergic action on keratinocytes by
      suppressing the production of certain proinflammatory cytokines, both Th1 and Th2
      chemokines, and possibly by inhibiting the expression of CD54.

PMID- 19088501
TI  - Indirect estimation of the area density of Atg8 on the phagophore.
AB  - Atg8 is a ubiquitin-like protein that controls the expansion of the phagophore
      during autophagosome formation. It is recruited to the phagophore during the
      expansion stage and released upon the completion of the autophagosome. One
      possible model explaining the function of Atg8 is that it acts as an adaptor of a
      coat complex. Here, we tested the coat-adaptor model by estimating the area
      density of Atg8 molecules on the phagophore. We developed a computational process
      to simulate the random sectioning of vesicles heterogeneous in size. This method
      can be applied to estimate the original sizes of intracellular vesicles from
      sizes of their random sections obtained through transmission electron microscopy.
      Using this method, we found that the estimated area density of Atg8 is comparable
      with that of proteins that form the COPII coat.

PMID- 19088503
TI  - Patient's page. Osteoporosis.

PMID- 19088502
TI  - A putative loop E motif and an H-H kissing loop interaction are conserved and
      functional features in a group C enterovirus RNA that inhibits ribonuclease L.
AB  - A phylogenetically conserved RNA structure within the open reading frame of
      poliovirus and other group C enteroviruses functions as a competitive inhibitor
      of the antiviral endoribonuclease RNase L. Hence, we call this viral RNA the
      RNase L competitive inhibitor RNA (RNase L ciRNA). In this investigation we used
      phylogenetic information, RNA structure prediction software, site-directed
      mutagenesis, and RNase L activity assays to identify functionally important
      sequences and structures of the RNase L ciRNA. A putative loop E motif is
      phylogenetically conserved in the RNA structure and mutations of nucleotides
      within the putative loop E motif destroyed the ability of the RNA molecule to
      inhibit RNase L. A putative H-H kissing loop interaction is phylogenetically
      conserved in the RNA structure and covariant polymorphisms that maintain the
      Watson-Crick complementarity required for the kissing interaction provide
      evidence of its importance. Compensatory mutations that disrupted and then
      restored the putative kissing interaction confirm that it contributes to the
      ability of the viral RNA to inhibit RNase L. RNase L was activated late during
      the course of poliovirus replication in HeLa cells, as virus replication and
      assembly neared completion. We conclude that a putative loop E motif and an H-H
      kissing loop interaction are key features of the group C enterovirus RNA
      associated with the inhibition of RNase L.

PMID- 19088508
TI  - B-type natriuretic peptide in end-stage renal disease: a neurohormone rather than
      a volume status monitor.

PMID- 19088509
TI  - Brain natriuretic peptide (BNP): a new risk marker in hemodialysis patients?

PMID- 19088510
TI  - Pneumonia in the elderly: whose friend is it anyway?

PMID- 19088511
TI  - Pneumonia in the elderly: understanding the characteristics.

PMID- 19088512
TI  - Acute acalculous cholecystitis after trauma: the role of microcirculatory failure
      and cellular hypoxia.

PMID- 19088513
TI  - The Brugada syndrome: an elusive diagnosis.

PMID- 19088514
TI  - Cystic adventitial disease: a cause for intermittent claudication in young ages.

PMID- 19088515
TI  - Drug-induced sexual problems.

PMID- 19088516
TI  - Blood B-type natriuretic peptide and dialysis: present assessment and future
      analyses.
AB  - Brain natriuretic peptide (BNP) is elevated in hemodialysis (HD) patients and
      predicts increased mortality. Intra- and interdialytic changes in BNP have not
      been fully described. End-stage renal disease (ESRD) patients were prospectively
      recruited at three dialysis centers. At five visits, over a 6-week period, pre-
      and postdialysis BNP levels were measured. Pre- and postdialysis weights, blood
      pressure, fluid removed/given and demographic/medical information were recorded.
      Mean pre- and post-HD BNP (log-transformed) was not significantly different and
      did not correlate with fluid removed. Both pre- and post-HD BNP significantly
      decreased across the dialysis week (Pre-HD: intercept = 2.69, slope = -0.097, t =
      -6.7, P < 0.001) and across the five sessions (slope = -0.046, t = -2.47, P =
      0.01). Interdialytic BNP changes are not related to fluid removed. Chronic volume
      overload and increased left ventricular wall tension likely account for the BNP
      decrease across dialysis weeks and may be related to higher death rates among HD
      patients at the beginning of the week.

PMID- 19088517
TI  - Influenza vaccine: awareness and barriers to immunization in families of children
      with chronic medical conditions other than asthma.
AB  - OBJECTIVES: Children with chronic medical conditions (CMCs) are considered to be
      at increased risk for influenza and its related complications. Despite this,
      influenza immunization rates in the United States for children with CMCs in the
      primary care setting remain between 7-10%. This was a survey study looking at the
      barriers to influenza immunization among children with CMCs other than asthma. We
      examined caregiver knowledge and perceptions regarding influenza vaccine in
      addition to assessing other barriers, such as availability and perceived safety
      of the vaccine. METHODS: The study was conducted during the fall-winter influenza
      seasons of 2002-2003 and 2003-2004 at five academic institutions across the
      southeastern US. Convenience samples of 100-150 families attending pediatric
      subspecialty clinics were surveyed. RESULTS: A total of 794 surveys were
      completed. Controlling for disease, failure to recommend vaccination was
      significantly associated with failure to get the vaccine (P < 0.0001). Of the
      children who did not receive the vaccine, 61% of their parents believed that the
      vaccine itself could give influenza, 54% cited other safety concerns, and 30%
      thought it did not work. Among vaccine recipients, 163 (43%) reported that the
      primary care provider had given the vaccine, whereas 171 (45%) reported that the
      vaccine had been given at the subspecialty clinic. CONCLUSION: This study
      highlights the importance of physician recommendation, as well as parental
      education, as some of the key elements crucial to the receipt of influenza
      vaccination in children with CMCs.

PMID- 19088518
TI  - Parental report of medication acceptance among youth: implications for everyday
      practice.
AB  - OBJECTIVE: Evidence-based interventions for pill swallowing training exist but
      are primarily implemented in pediatric specialty hospitals. Given increasing
      interest in the translation of brief and effective interventions to the wider
      population, there is a need to examine medication acceptance in a normative
      sample. METHODS: Participants (N = 304) completed the Medication Acceptance
      Survey, which assessed child/adolescent liquid and pill medication history and
      acceptance as well as parental interest in pill swallowing training. RESULTS:
      Results showed that 30-40% of youth had rejected/refused a pill or liquid
      formulation. Over half were unable to swallow a standard size pill or small
      capsule. Despite these difficulties, most parents did not express interest in an
      empirically supported pill swallowing training intervention. CONCLUSIONS: The
      results provide directions for future research as well as the translation of pill
      swallowing interventions to primary care.

PMID- 19088519
TI  - Abdominal aortic aneurysm and significant coronary artery disease: strategies and
      options.
AB  - OBJECTIVES: The optimal treatment for patients requiring intervention for
      coronary artery disease (CAD) and concomitant large or symptomatic abdominal
      aortic aneurysm (AAA) remains problematic. METHODS: Retrospective analysis was
      performed of 32 patients with symptomatic or large (> cm) AAA along with
      significant CAD treated over the past fifteen years at a university hospital.
      RESULTS: Mean AAA diameter was 6.6 cm. CAD involved 3 or more vessels in all
      patients. Fifteen patients underwent staged coronary artery bypass grafting
      (CABG) followed by open AAA repair, with two (13%) dying as a result of aneurysm
      rupture in the early postoperative period. No major complications were
      encountered among five patients receiving staged coronary angioplasty before open
      AAA repair and two patients undergoing staged CABG followed by endovascular
      aneurysm repair. Ten patients underwent concomitant CABG and AAA repair, with a
      single intraoperative death (10%). No differences in morbidity were observed
      among patients undergoing concomitant procedures as compared with those subjected
      to staged procedures. CONCLUSIONS: Minimally invasive interventions for coronary
      revascularization and aortic aneurysm repair appear to be safe and effective
      options in properly selected high-risk patients. While optimal management must be
      individualized, these data suggest that either staged or concomitant CABG and AAA
      repair may be viable options when minimally invasive interventions are not
      feasible.

PMID- 19088520
TI  - The role of ankle-brachial index as a screening test for coronary artery disease
      in the Hispanic population.
AB  - OBJECTIVES: This study evaluated the role of ankle-brachial index (ABI) as an
      effective screening test of coronary artery disease (CAD) in the Hispanic
      population. METHODS: This was an observational cross-sectional study, based on a
      retrospective review of the medical management of the study patients using
      already available data. The study comprised 155 patients, aged 50 to 70 years
      with metabolic syndrome but no known CAD, presenting in El Paso, Texas between
      February 2004 and November 2006. An ABI test had been performed on all the
      patients in this study. Also, myocardial nuclear perfusion imaging using single
      photon emission computed tomography and electrocardiogram gating tests had been
      performed on these patients, because they all had multiple traditional risk
      factors for CAD. RESULTS: Sensitivity of low ABI in screening for CAD was 82.61%,
      while the specificity was 77.27%. CONCLUSION: ABI is an effective and cost
      efficient screening test for CAD.

PMID- 19088521
TI  - Avian flu: how informed are children in Greece?
AB  - OBJECTIVES: The current cluster of avian influenza outbreaks in birds has
      occurred in areas where humans live in proximity to poultry. Dissemination of
      accurate information may be the cornerstone for proper community preparation. In
      the herein presented study, we attempted to asses the information level among
      Greek children regarding avian flu. METHODS: A descriptive study was carried out
      in 2006 in ten Greek prefectures to determine the information level among
      students about transmission ways, symptoms and prevention measures of avian flu.
      RESULTS: A total of 1400 Greek students participated in the study. Approximately
      75% of the students reported to know what bird flu is and 53% reported to know
      that there has been at least one case of avian flu in Greece. More than half
      (55.6%) reported that an effective vaccine against avian flu does exist; of the
      students asked, 47% reported that avian flu can be transmitted from human to
      human whereas 21.4% believed that humans can suffer from avian flu. Media
      contribution in providing information was very high among students. CONCLUSION:
      The level of information about avian flu among Greek students was found
      inadequate especially in some questions regarding serious aspects of avian flu.
      This study highlights the need for adaptation of health programs in Greek
      schools, which should include the provision of accurate information.

PMID- 19088522
TI  - Prophylactic antibiotics in necrotizing pancreatitis: a meta-analysis.
AB  - PURPOSE: Prophylactic antibiotics have been used in acute necrotizing
      pancreatitis with mixed results. This meta-analysis analyzes the effects of
      prophylactic antibiotics in necrotizing pancreatitis. METHODS: Multiple databases
      and abstracts were searched for randomized trials comparing treatment with
      prophylactic antibiotics to treatment without prophylactic antibiotics in
      necrotizing pancreatitis. Prophylactic antibiotics' effects were analyzed by
      calculating pooled estimates of mortality, infected pancreatic necrosis, length
      of hospital stay, nonpancreatic infections, and surgical intervention. RESULTS:
      Seven studies (n = 429) met the inclusion criteria. Prophylactic antibiotics for
      acute necrotizing pancreatitis significantly decreased the length of hospital
      stay (P = 0.04) and the rate of nonpancreatic infections (P < 0.01). No
      significant differences were noted for mortality (P = 0.22), infected necrosis (P
      = 0.18), and surgical intervention (P = 0.40). CONCLUSIONS: Prophylactic
      antibiotics in necrotizing pancreatitis reduced the length of hospital stay and
      rate of nonpancreatic infections but did not decrease mortality, infected
      necrosis, or surgical intervention.

PMID- 19088524
TI  - Pneumonia in the elderly: a review of severity assessment, prognosis, mortality,
      prevention, and treatment.
AB  - Pneumonia is an increasingly common disease in the elderly due to an aging
      population. This is a comprehensive literature review outlining the severity
      assessment, morbidity, mortality, prevention and treatment options. Several
      models have been postulated to predict severity assessment and prognosis in older
      patients. Mortality increases with age and functional status is also an
      independent predictor for short- and long-term mortality. The effectiveness of
      the pneumococcal vaccine is controversial, whereas the influenza vaccine is
      universally recommended. Treatment involves antibiotics with the type and method
      depending on the severity of the pneumonia. However, treatment of nursing home
      patients is challenging and there are no validated guidelines at present to
      determine when transfer to the hospital is necessary.

PMID- 19088525
TI  - Pneumonia in the elderly: a review of the epidemiology, pathogenesis,
      microbiology, and clinical features.
AB  - Pneumonia is a common and important disease in the elderly. The incidence is
      expected to rise as the population ages, and, therefore, it will become an
      increasingly significant problem in hospitals and the community. A comprehensive
      literature review was performed in order to look at the characteristics of
      pneumonia in the elderly population. In particular, the epidemiology, etiology
      and pathogenesis--including risk factors, microbiology, and clinical features-
      were evaluated. While aging causes physiological changes which make elderly
      patients more susceptible to pneumonia, it was found that comorbidities, rather
      than age, are also an important risk factor. The most common micro-organism
      responsible for pneumonia is Streptococcus pneumoniae, but other organisms need
      to be considered, depending on the environment of presentation. Elderly patients
      are more likely than younger adults to present with an absence of fever and an
      altered mental state. Nursing home residents tend to present with more atypical
      and less characteristic symptoms.

PMID- 19088526
TI  - Acute acalculous cholecystitis complicating major trauma: a report of five cases.
AB  - The purpose of this study was to identify the clinical characteristics of the
      patients in our institution who developed acute acalculous cholecystitis (AAC)
      after major trauma. Data of all trauma patients who developed AAC from January
      2001 through June 2006 were analyzed. Five out of 1386 (0.3%) major trauma
      patients were diagnosed with AAC. One out of five patients had hypotension and
      shock and received vasopressor treatment. Prior to the diagnosis of AAC, all
      patients received ventilatory support, intravenous opioid analgesia, had
      pneumonia, and experienced tachycardia. No specific clinical characteristic was
      identified in patients with AAC; however, prolonged ventilatory support,
      pneumonia, use of opioids, and new onset arrhythmias were seen in the majority of
      patients.

PMID- 19088527
TI  - Woman with Brugada syndrome and epilepsy: a unifying diagnosis?
AB  - A woman with a past medical history of epilepsy was transferred to our hospital
      for episodic changes in mental status, jerking movements, and decreased hearing
      that were thought to represent seizure activity. While in the hospital, she was
      diagnosed with Brugada syndrome. Her antiepileptic medications were adjusted
      while she was monitored on constant electroencephalography, video, and cardiac
      telemetry. It was found that the patient's seizures were not caused by
      hypoperfusion of her brain secondary to cardiac arrhythmia. Instead, we theorize
      that she had an underlying systemic, genetic sodium ion channel dysfunction.

PMID- 19088528
TI  - Popliteal cystic adventitial disease causing intermittent claudication in a young
      athlete: a case report.
AB  - Cystic adventitial disease (CAD) is a rare condition that usually affects the
      popliteal artery and presents with symptoms of intermittent claudication in the
      younger population. Here, we present the case of a young athlete with popliteal
      cystic adventitial disease and discuss available treatment options.

PMID- 19088529
TI  - Peyronie disease in association with carvedilol: a case report.
AB  - Beta blockade is associated with the onset and progression of Peyronie disease
      (PD). To date, there has not been a report of PD occurring with the alpha/beta
      blocker carvedilol. It remains unproven but likely that carvedilol was the cause
      of the PD in the patient described in this case. It is hypothesized that because
      of carvedilol's vasodilating alpha adrenergic receptor stimulation and its anti
      inflammatory effect, PD occurs less frequently with carvedilol than with other
      beta blockers. However, in this case the protective properties of carvedilol,
      like vasodilation and the anti-inflammatory effect, may not be sufficient to
      overcome its vasoconstricting beta adrenergic receptor blockade.

PMID- 19088530
TI  - Esophageal squamous cell carcinoma with a solitary phalangeal metastasis.
AB  - A patient with pathologically proven acrometastasis of his left thumb presented 3
      months after esophagectomy for esophageal squamous cell carcinoma. Interestingly,
      there was indeed a faint uptake in his left thumb that was initially considered
      an artifact in the whole body bone scan taken before esophagectomy. Physicians
      must be aware of the possibility of acrometastasis, even if there is no other
      concomitant metastatic area.

PMID- 19088531
TI  - Systemic lupus erythematosus associated with paclitaxel use in the treatment of
      ovarian cancer.
AB  - Over the last years, scleroderma-like skin changes have been reported with two of
      the taxanes, docetaxel and paclitaxel, but specific antibodies were not found in
      any of those cases. Recently, paclitaxel was linked to cutaneous lupus
      erythematosus in two cancer patients, showing high titers of serum anti-Ro (SS-A)
      antibody. To our knowledge, this is the first known case of a patient with
      serologically confirmed systemic lupus erythematosus secondary to paclitaxel use.

PMID- 19088532
TI  - Cardiac tamponade caused by fracture and migration of inferior vena cava filter.
AB  - A 53-year-old male presented to the emergency room with acute cardiopulmonary
      compromise. Echocardiography revealed cardiac tamponade. The patient was taken
      emergently for surgery and a 28 gauge wire of 1.5 cm was retrieved from his right
      ventricle. A section had fractured from the inferior vena cava (IVC) filter and
      migrated to the right ventricle, causing perforation and tamponade. Very few
      cases of fractured IVC filters that have migrated to the heart, and even fewer
      cases causing cardiac tamponade, have been described. The risk factors that cause
      migration of IVC filters need to be further elucidated.

PMID- 19088533
TI  - Stenting for coronary intervention-related dissection of the left main coronary
      artery with extension to the aortic root: a case report.
AB  - Retrograde aortocoronary dissection is a rare but devastating complication of
      coronary angioplasty. It occurs most frequently in the right coronary artery,
      rarely in the left. This is a case report of an aortic dissection complicated by
      coronary angioplasty of the left circumflex artery. Stenting of the left main
      coronary artery successfully sealed the entry point of dissection.

PMID- 19088534
TI  - Nonpolypoid intestinal mantle cell lymphoma resembling MALT lymphoma with
      successful response to rituximab.
AB  - Two unusual cases of mantle cell lymphoma are reported. They involved the ileum
      and right colon without multiple lymphomatous polyposis and morphologically
      resembled an extranodal marginal zone B-cell lymphoma of mucosa-associated
      lymphoid tissue (MALT) type.

PMID- 19088535
TI  - Gastric carcinoid tumor in association with hepatocellular carcinoma: a case
      report.
AB  - A second primary malignancy (SPM) can occur in patients with gastrointestinal
      carcinoids. A patient underwent endoscopic resection of a gastric carcinoid.
      Repeat gastroscopy revealed recurrence of the lesion and multiple nodular gastric
      lesions, while an abdominal computed tomography scan revealed a small solid
      lesion in the left hepatic lobe. The patient underwent total gastrectomy and
      wedge resection of what proved to be a hepatocellular carcinoma. This case
      illustrates the significance of considering SPM in every patient with
      gastrointestinal carcinoids. SPMs are more aggressive than carcinoids, and
      awareness and early resection of these tumors may improve prognosis.

PMID- 19088536
TI  - Entecavir therapy in a hepatitis B-related decompensated cirrhotic patient.
AB  - A 58-year-old Arab-American male with HBeAg-negative chronic hepatitis B (HBV),
      presented with decompensated cirrhosis and a high HBV DNA level. He responded to
      entecavir with a significant reduction in serum HBV DNA level after 15 weeks of
      therapy with entecavir. However, he developed a progressive rise in prothrombin
      time/international normalized ratio (PT/INR) and bilirubin and underwent liver
      transplantation after receiving 22 weeks of entecavir therapy. Furthermore, with
      the continued use of combination entecavir and hepatitis B immunoglobulins
      (HBIG), he showed improvement in his clinical status with a nondetectable serum
      HBV DNA level 12 weeks after transplantation. He continued to maintain
      nondetectable serum HBV DNA 2 years following transplantation. To the best of our
      knowledge, this is the first reported case of a patient with decompensated
      chronic HBV who responded to entecavir both before and after transplantation
      without showing any evidence of recurrent HBV. Larger clinical trials are
      recommended to compare both short-term and long-term efficacy using entecavir
      among nucleoside-naive decompensated chronic HBV patients before and after liver
      transplantation.

PMID- 19088537
TI  - Right atrial intramural hematoma associated with aortic dissection.
AB  - A 75-year-old male presented with shortness of breath and abdominal pain; he had
      undergone coronary artery bypass graft surgery three months ago and had a history
      of coronary artery disease, hypertension, and end-stage renal disease.
      Transthoracic echocardiogram showed a right atrial mass. A computed axial
      tomography scan showed an atrial mass and type A aortic dissection. The patient
      sustained cardiorespiratory arrest and died. An autopsy showed an 8 cm atrial
      intramural hematoma originating from a dissecting aneurysm. This is the first
      case of right atrial intramural hematoma associated with aortic dissection
      exhibiting high mortality. Early diagnosis using multiple imaging modalities
      including magnetic resonance imaging and timely surgical intervention may improve
      survival. Intramural hematomas should be considered in patients presenting with
      right-sided cardiac lesions.

PMID- 19088538
TI  - Multiple painful cutaneous facial papules.
AB  - A 21-year-old female with linear, flesh-colored papules on her face was diagnosed
      with cutaneous piloleiomyoma. Important associations for physicians to be aware
      of include uterine leiomyomas, leiomyosarcomas, and renal cell carcinoma.
      Mutations for this syndrome have been mapped to the fumarate hydratase gene.

PMID- 19088539
TI  - Single metastasis in the gallbladder arising from adenocarcinoma of the rectum.

PMID- 19088540
TI  - Brugada syndrome, epilepsy and pemphigus vulgaris.

PMID- 19088541
TI  - Aortic dissection presenting with new onset atrial fibrillation: a very unusual
      presentation.

PMID- 19088542
TI  - Anal pap smear in high-risk patients: a poor screening tool.

PMID- 19088543
TI  - Myocarditis due to Bartonella henselae.

PMID- 19088544
TI  - Secondary psoas abscess.

PMID- 19088545
TI  - Outcome predictors of chronic renal disease patients with parapneumonic empyemas.

PMID- 19088546
TI  - Niemann-Pick disease type B presenting with hepatosplenomegaly and
      thrombocytopenia.

PMID- 19088548
TI  - Aortoiliac reconstruction for abdominal aortic rupture after blunt trauma.

PMID- 19088549
TI  - Clavicular nonunion associated with thoracic outlet syndrome treated with Knowles
      pin fixation, autogenous bone marrow graft, and autologous fibrin clots.

PMID- 19088550
TI  - Outcome after injury: memories, health-related quality of life, anxiety, and
      symptoms of depression after intensive care.
AB  - BACKGROUND: To examine the relationship between delusional memories from the
      Intensive Care Unit (ICU) stay, health related quality of life (HRQoL), anxiety,
      and symptoms of depression in patients with physical trauma, 6 months to 18
      months after their ICU stay. METHODS: Multicenter study in five combined medical
      and surgical ICUs (n = 239). A questionnaire comprising the Medical outcome Short
      Form 36, the Hospital Anxiety and Depression scale, and the Intensive Care Unit
      Memory tool was sent to the patients with trauma 6 months to 18 months after
      their discharge from the ICU. Clinical data were drawn from patient records in
      retrospect. A matched reference sample (n = 159) was randomly drawn from the
      Swedish Short Form 36 norm database (n = 8,930). RESULTS: Patients with trauma
      had significantly lower HRQoL than the reference sample. One or more delusional
      memories such as hallucinations, nightmares, dreams, or sensations of people
      trying to hurt them in the ICU were experienced by 26%. These patients were
      significantly younger, had a longer ICU stay, relied more on mechanical
      ventilation, and had higher Injury Severity Score and Sequential Organ Failure
      Assessment scores. They also reported a significantly poorer HRQoL and a higher
      probability of experiencing anxiety (51% vs. 29%) and symptoms of depression (48%
      vs. 26%) compared with patients without such memories. CONCLUSIONS: Our results
      highlight the importance of treating the delusional memories experienced by ICU
      patients with a trauma diagnosis as a postinjury factor with a potential to
      create anxiety and symptoms of depression and which may affect HRQoL after
      discharge.

PMID- 19088551
TI  - The relationship between remoteness and trauma deaths in Western Australia.
AB  - BACKGROUND: Mortality from trauma in rural areas is increased compared with the
      urban environment. We aimed to describe the relationship between trauma deaths
      and various categories of remoteness in rural areas, in Western Australia (WA).
      METHODS: We used Death Registry data from July 1, 1997 to June 30, 2006. Deaths
      were allocated to one of the five Remoteness Areas classified by the
      Accessibility/ Remoteness Index of Australia: Major Cities, Inner Regional, Outer
      Regional, Remote, and Very Remote. Population data were obtained from the
      Australian Bureau of Statistics 2001 census. RESULTS: There were 4,937 deaths
      (3,543, 71.8% men; mean age 43.4 years +/- 24.3 years). The least number of
      deaths occurred in Remote WA, and the age at which death occurred decreased as
      remoteness increased. Falls occur predominantly in the elderly in the major city.
      Transport injuries are the leading cause of death (43.3%) outside the major city,
      where self harm is the leading cause of death (31.2%). The relative risk for
      death in very remote WA compared with the major city is 4.28 (95% CI 3.93-4.68).
      The standardized age-specific death rates ranged from 24.09 per 100,000 person
      years in the major city, to 103.30 per 100,000 person-years in very remote WA.
      CONCLUSIONS: We have quantified the direct relationship between remoteness and
      trauma deaths. In particular, the death rate in very remote areas is over four
      times the rate in major cities. Such data should be useful for the planning of
      trauma systems in these areas.

PMID- 19088552
TI  - Treatment of infection of the ankle joint after subtotal talectomy using the free
      gracilis muscle: a case report from Hanoi, Vietnam.

PMID- 19088553
TI  - Adolescent lumbar chance lesion: recurrent instability after hardware removal.

PMID- 19088554
TI  - Decompressive laparotomy to treat intractable cerebral hypoxia.

PMID- 19088555
TI  - Revival from deep hypothermia after 4 hours of cardiac arrest without the use of
      extracorporeal circulation.

PMID- 19088556
TI  - An unusual presentation of a thoracic vertebral body fracture in a patient with
      diffuse idiopathic skeletal hyperostosis.

PMID- 19088557
TI  - Intracerebral hemorrhage following electrical head injury.

PMID- 19088558
TI  - Images of trauma: Multiple self-inflicted injuries in an incarcerated man.

PMID- 19088559
TI  - Angular shortening and delayed gradual distraction for the treatment of
      asymmetrical bone and soft tissue defects of tibia: a case series.
AB  - BACKGROUND: Acute shortening is reported to be an effective method for the
      treatment of open fractures with bone and soft tissue defects. Little is known
      about primary skin closure with angulation to the side of the defect and
      distraction at the fracture site. METHODS: We present a series of three cases
      treated for defective fractures of tibia by angular shortening and delayed
      gradual distraction with hinged circular external fixator. Two cases were type
      IIIB open fractures and one case was an infected nonunion. Bone and soft tissue
      defects were managed by adaptation of edges and primary skin closure with
      angulation to the side of the defect. Axial alignment was restored by gradual
      distraction after a 2 to 3 weeks interval. Residual limb length discrepancy was
      lengthened through a separate corticotomy in two cases. RESULTS: Bone formation
      at both the fracture and corticotomy sites were sufficient to achieve union in
      all patients. Fixation time averaged 261 (182-392) days and average bone healing
      index was 42 days/cm. No further surgical intervention was necessary for soft
      tissue reconstruction after primary skin closure. Infection was eradicated in the
      case of infected nonunion. CONCLUSIONS: Angular compression to the side of the
      defect is a safe and reliable method of treatment for asymmetrical bone or soft
      tissue defects of tibia. It eliminates the need for complex soft tissue
      reconstruction procedures. Unnecessary debridement of bone is prevented by
      angular adaptation of edges. Definitive treatment of complex injuries is possible
      with a circular external fixator.

PMID- 19088560
TI  - Simultaneous craniotomy and caesarean section for trauma.

PMID- 19088561
TI  - Extracorporeal life support as a treatment for neurogenic pulmonary edema and
      cardiac failure secondary to intractable intracranial hypertension: a case report
      and review of the literature.

PMID- 19088562
TI  - Mandibular fractures in severely developmentally disabled persons.

PMID- 19088563
TI  - Traumatic Rupture of an Augmented Bladder: Computed Tomography Appearances.

PMID- 19088564
TI  - The future's here. We are it.

PMID- 19088565
TI  - A letter from the president of the society for medical simulation.

PMID- 19088566
TI  - A model for educational simulation of neonatal cardiovascular pathophysiology.
AB  - Full-body patient simulators provide a technological basis for clinical education
      without risk to real patients. In a previous study, we described a model for
      educational simulation of infant cardiovascular physiology. Using essentially the
      same methodology, we derive a mathematical model for the cardiovascular system of
      a healthy 1-week-old neonate. Computer simulations of this model result in vital
      signs that are close to target hemodynamic variables. Simulated systemic arterial
      pressure waveform and left ventricular pressure-volume loop are realistic, and
      the system reacts appropriately to blood loss. We also adapt the model structure
      and change its parameters to reflect the congenital heart defects: patent ductus
      arteriosus, tetralogy of Fallot, complex coarctation of the aorta with patent
      foramen ovale, and transposition of the great arteries. Simulated vital signs are
      again close to target hemodynamic variables. The resulting model for neonatal
      cardiovascular pathophysiology is an essential step in attaining a full-body,
      model-driven neonatal acute care simulator.

PMID- 19088567
TI  - Can a simulated critical care encounter accelerate basic science learning among
      preclinical medical students? A pilot study.
AB  - PURPOSE: To explore whether a simulated critical care encounter can accelerate
      basic science learning among preclinical medical students. METHOD: Using a high
      fidelity patient simulator, we "brought to life" a paper case of a myocardial
      infarction among a convenience sample of first-year medical students (n=22
      [intervention]). Students discussed the case as part of a routine tutorial
      session, and then managed the case in the simulator laboratory. Using an
      identical six-item test of cardiac physiology, students were evaluated
      immediately after the simulator session and at 1 year (n=15). Performance was
      compared with controls (case discussion but no simulator session) at both
      baseline (n=37) and 1 year (n=48). RESULTS: Performance among simulator-exposed
      students was significantly enhanced on immediate testing (mean score 4.0
      [control], 4.7 [intervention], P = .005). Gains among the simulator cohort were
      maintained at 1 year (mean score 4.1 [control], 4.7 [intervention], P = .045).
      Multivariable analysis confirmed that the intervention was a significant
      determinant of performance across time (P = .001). CONCLUSION: Compared with
      controls in this pilot study, an additional simulation exercise improved
      immediate performance on a short written test of cardiovascular physiology.
      Enhanced performance was again seen at 1 year, raising the possibility that the
      extra teaching session produced accelerated and sustained learning compared with
      the routine teaching method. Given the preliminary nature of this investigation,
      further study is required to distinguish transient from lasting effects of
      simulation versus alternative teaching approaches in the basic medical sciences.

PMID- 19088568
TI  - The status of human simulation training in emergency medicine residency programs.
AB  - INTRODUCTION: : The objective of this study was to describe the availability and
      current use of high-fidelity mannequin-based simulation (HFMB) in emergency
      medicine (EM) training programs. METHODS: : A 12-item survey instrument was used
      to collect data on the status of human simulation training at the 126 approved EM
      residencies and the 30 accredited osteopathic EM residencies. RESULTS: : In all,
      114 out of 156 programs completed the survey for a response rate of 73%. There
      are 54 (47%) EM training programs with HFMB simulators at their institution, 38
      (33%) EM training programs with access to these HFMB simulators, and 33 (29%) EM
      training programs that have EM residents use HFMB simulators. The Department of
      Anesthesia manages the HFMB simulator at 19 (17%) institutions. EM manages the
      HFMB simulator at nine (8%) institutions. EM residents are using HFMB simulation
      every 1-2 weeks at three (8%) programs, every 1-4 months at 16 (42%) programs,
      yearly at nine (24%) programs, and not regularly at 10 (26%) programs. The
      simulation curriculum is described as "no formal curriculum" or "initial
      development" in 60% of programs. CONCLUSION: : HFMB simulation technology has not
      been completely adopted by EM training programs even when it is available. Most
      EM training programs are using HFMB simulation less often than every month and
      curriculum development in EM training is still in the early phases.

PMID- 19088569
TI  - So many roads: facilitated debriefing in healthcare.

PMID- 19088570
TI  - Clinicians' recognition of the Ohmeda Modulus II plus and Ohmeda Excel 210 SE
      anesthesia machine system mode and function.
AB  - INTRODUCTION: : Anesthesiologists' cognitive resources such as their attention,
      knowledge, and strategies play an important role in the prevention and correction
      of critical events. In this paper, we examined anesthesiologists' responses to
      the anesthesia machine (AM) in the "off" position during a simulated emergent
      cesarean section scenario. METHODS: : All simulations were videotaped which
      allowed for offline review. At the beginning of the scenario, the AM system
      switch was purposefully turned to the off/standby position. The responses of 14
      anesthesia residents at the Veterans Affairs Palo Alto Health Care System and
      Stanford University Simulation Center for Crisis Management Training in Health
      Care (VASC) and 11 anesthesia residents at the Boston Center for Medical
      Simulation (CMS) were analyzed. RESULTS: : Nine subjects at VASC restored the AM
      system switch to the "on" position on their own, whereas five subjects required
      help from another clinician. The median response time (RT) for all 14 subjects
      was 149.5 seconds. At CMS, five subjects restored the AM system switch to the
      "on" position on their own (median RT = 207 seconds), whereas two subjects
      received help from another anesthesia resident. There were four cases where the
      AM system switch problem was not corrected. CONCLUSIONS: : Factors that could
      have contributed to subjects' difficulty in detecting and correcting the AM
      system switch included the unusual nature of the problem, the human factors
      design of the AM front panel and system switch, and inadequate training by the
      subjects. Improving the appearance of the AM's system switch and training of
      clinicians to recognize the location and functionality of the AM system switch
      could be useful in correcting such an event in a timely manner and reducing
      patient risk.

PMID- 19088571
TI  - Additional training with an obstetric simulator improves medical student comfort
      with basic procedures.
AB  - OBJECTIVE: To determine if an obstetric birthing simulator can improve medical
      student understanding of and comfort with basic obstetric procedures. STUDY
      DESIGN: Medical students were surveyed at the end of their obstetrics rotation
      regarding their knowledge and comfort with basic obstetric procedures. A group of
      students was trained on basic procedures utilizing an obstetric simulator. Survey
      results were compiled and analyzed with the Mann-Whitney U test. RESULTS: In all,
      60 untrained students and 18 simulator trained students completed surveys.
      Trained students were significantly more comfortable with fundal height
      measurements (P = 0.003), Leopold maneuvers (P < 0.001), fetal scalp electrode
      placement (P < 0.001), intrauterine pressure catheter placement (P < 0.001), and
      artificial rupture of membranes (P = 0.001) and reported better understanding of
      the indications for placement of a fetal scalp electrode (P = 0.01) and
      intrauterine pressure catheter (P = 0.03). CONCLUSIONS: Additional training with
      an obstetric simulator improved medical student self-reported comfort with and
      understanding of basic procedures compared with standard resident and staff
      directed instruction.

PMID- 19088572
TI  - Development of a sympathetic response to laryngoscopy and endotracheal tube
      placement in a patient simulator.
AB  - Anesthesiologists have long recognized that there is a sympathetic response to
      stimulation of the larynx, even in sedated patients. This response creates a
      rapid increase in blood pressure and heart rate in these patients. For the last
      40 years, various simulation systems have been used to train anesthesiologists in
      the skills to be successful practitioners, simulating various disease states and
      crisis conditions. However, these systems do not contain this well-recognized
      sympathetic response to laryngoscopy and intubation. Using several experienced
      anesthesiologists as subject matter experts, we have developed a scenario that
      mimics this response for several types of patients. This scenario runs on the
      Medical Education Technologies, Inc. (METI) patient simulators; however, the
      methodology used to develop this scenario applies to other patient simulator
      systems.

PMID- 19088573
TI  - Using a mannequin-based simulator for anesthesia resident training in cardiac
      anesthesia.
AB  - Simulators are used for training medical personnel. This report details the use
      of a human patient simulator for initial clinical experience of anesthesia
      housestaff with cardiopulmonary bypass.

PMID- 19088574
TI  - There's no such thing as "nonjudgmental" debriefing: a theory and method for
      debriefing with good judgment.
AB  - We report on our experience with an approach to debriefing that emphasizes
      disclosing instructors' judgments and eliciting trainees' assumptions about the
      situation and their reasons for acting as they did. To highlight the importance
      of instructors disclosing their judgment skillfully, we call the approach
      "debriefing with good judgment." The approach draws on theory and empirical
      findings from a 35-year research program in the behavioral sciences on how to
      improve professional effectiveness through "reflective practice." This approach
      specifies a rigorous self-reflection process that helps trainees recognize and
      resolve pressing clinical and behavioral dilemmas raised by the simulation and
      the judgment of the instructor. The "debriefing with good judgment" approach is
      comprised of three elements. The first element is a conceptual model drawn from
      cognitive science. It stipulates that the trainees' "frames"--comprised of such
      things as knowledge, assumptions, and feelings--drive their actions. The actions,
      in turn, produce clinical results in a scenario. By uncovering the trainee's
      internal frame, the instructor can help the learner reframe internal assumptions
      and feelings and take action to achieve better results in the future. The second
      element is a stance of genuine curiosity about the trainee's frames. Presuming
      that the trainee's actions are an inevitable result of their frames, the
      instructor's job is that of a "cognitive detective" who tries to discover,
      through inquiry, what those frames are. The instructor establishes a "stance of
      curiosity" in which the trainees' mistakes are puzzles to be solved rather than
      simply erroneous. Finally, the approach includes a conversational technique
      designed to bring the judgment of the instructor and the frames of the trainee to
      light. The technique pairs advocacy and inquiry. Advocacy is a type of speech
      that includes an objective observation about and subjective judgment of the
      trainees' actions. Inquiry is a genuinely curious question that attempts to
      illuminate the trainee's frame in relation to the action described in the
      instructor's advocacy. We find that the approach helps instructors manage the
      apparent tension between sharing critical, evaluative judgments while maintaining
      a trusting relationship with trainees.

PMID- 19088575
TI  - The Oregon simulation experience: a statewide simulation network and alliance.

PMID- 19088576
TI  - GE Healthcare comments on clinicians' recognition of the Ohmeda Modulus II plus
      and Ohmeda Excel 210 SE anesthesia machine system mode and function.

PMID- 19088577
TI  - A new name.

PMID- 19088578
TI  - What's in a name? A mannequin by any other name would work as well.

PMID- 19088579
TI  - Evaluation of a framework for case development and simulated patient training for
      complex procedures.
AB  - BACKGROUND: Simulation for training and assessing clinicians is increasing but
      often overlooks the patient's perspective. In this paper, actors are trained to
      portray patients undergoing operations under local anesthetic within a high
      fidelity simulated operating theater (SOT). There are few published accounts of
      approaches to case development and simulated patient (SP) training. We assess the
      feasibility of SPs playing complex surgical roles and evaluate a three-phased
      framework for case development and SP training. METHODS: We developed two patient
      roles for carotid endarterectomy (CEA) under local anesthesia. In all cases, the
      conscious patient interacted with the surgical team throughout the procedure. SPs
      were trained to simulate routine and crisis situations, using our framework.
      After consulting with each SP, surgeons "performed" a CEA upon a model attached
      to the SP. Evaluation of the framework used interviews, observations, and written
      evaluations with SPs, surgeons, and the project team. Descriptive statistics
      summarize surgeons' ratings of realism and qualitative data are analyzed
      thematically. RESULTS: In all, 46 simulations were conducted with 23 surgeons and
      three SPs. Real patient interview transcripts provided SPs with authentic
      information. The SP framework was easy to use, SP training was successful and
      surgeons' rated SP realism very highly. SPs valued guidance from the SOT control
      room using an audiolink. CONCLUSIONS: Actors can be trained to portray patients
      undergoing complex procedures. Our framework for case development and SP training
      was effective in creating realistic roles. Future studies could evaluate this
      framework for additional procedures.

PMID- 19088580
TI  - Multipatient disaster scenario design using mixed modality medical simulation for
      the evaluation of civilian prehospital medical response: a "dirty bomb" case
      study.

PMID- 19088581
TI  - Integrating echocardiography into human patient simulator training of
      anesthesiology residents using a severe pulmonary embolism scenario.
AB  - INTRODUCTION: Echocardiographic images were integrated into patient simulation
      (PS)-based resident training with a goal of highlighting the applicability and
      limitations of pure pressure-based measurements in the management of different
      disease states. METHODS: Relevant echocardiographic images were selected,
      categorized, and sequenced to best represent specific hemodynamic changes and
      incorporated into a Powerpoint slideshow. Appropriate PS scenarios were then
      created to represent the hemodynamic changes seen with the selected
      pathophysiologic states. Instructors then displayed the visual images along with
      PS scenarios during lecture and testing sessions at the PS bedside during
      standard didactic sessions with small groups of anesthesiology residents and
      informal resident testing sessions. CONCLUSIONS: The use of echo images to
      demonstrate, in real time, the hemodynamic consequences of changes in myocardial
      contractility, cardiac chamber volume, and valvular function is possible during
      PS in anesthesiology residency training. Echo imaging as a teaching tool during
      anesthesiology residency may yield a greater understanding of the pathophysiology
      of certain disease states, ultimately leading to faster diagnosis and more
      appropriate intervention by anesthesiologists.

PMID- 19088582
TI  - A little bit farther than we've gone before.

PMID- 19088583
TI  - Face and content validation of virtual reality simulation for carotid
      angiography: results from the first 100 physicians attending the Emory
      NeuroAnatomy Carotid Training (ENACT) program.
AB  - BACKGROUND: Increasing time and resource constraints, and the potential for
      patient complications, has led to an emphasis on finding innovative ways to teach
      catheter-based procedures outside of the laboratory. Virtual reality (VR)
      simulator training has been proposed as a potential training solution. We report
      on the initial validation of a full procedural VR simulator for carotid
      angiography (CA) using the Vascular Interventional System Trainer (VIST).
      METHODS: In all, 100 experienced physicians, currently performing endovascular
      procedures (71 cardiologists, 29 surgeons, and one radiologist), underwent
      simulator based training in CA. Each operator completed three VR simulated CAs,
      and assessed the VIST VR simulator for both its face and content validity.
      RESULTS: Assessment involved how the carotid procedure simulation looked and felt
      as well as how catheters behaved during the completion of the CA. Assessment was
      rated on a five-point Likert scale. Anatomically, physicians reported that the
      aortic arch and carotid vasculature were well simulated (mean = 4.4). However,
      the bony structures and intra-cranial vasculature correlated poorly with actual
      anatomic structures (means = 2.3 and 1.1, respectively). One-to-one haptic
      correspondence of catheters during psychomotor movements were felt to be strongly
      representative of live procedures. The simulated sequence of using guidewires and
      catheters was rated to be nearly identical to actual CA (means = 4.8).
      CONCLUSIONS: VIST represents one of the most sophisticated VR simulators in
      medicine. Physicians reported that it looked, felt, and behaved similar to
      working on an actual patient. Future work is required to validate whether this
      simulator will improve catheter performance on actual patients.

PMID- 19088584
TI  - Asthma management simulation for children: translating theory, methods, and
      strategies to effect behavior change.
AB  - Translating behavioral theories, models, and strategies to guide the development
      and structure of computer-based health applications is well recognized, although
      a continued challenge for program developers. A stepped approach to translate
      behavioral theory in the design of simulations to teach chronic disease
      management to children is described. This includes the translation steps to: 1)
      define target behaviors and their determinants, 2) identify theoretical methods
      to optimize behavioral change, and 3) choose educational strategies to
      effectively apply these methods and combine these into a cohesive computer-based
      simulation for health education. Asthma is used to exemplify a chronic health
      management problem and a computer-based asthma management simulation (Watch,
      Discover, Think and Act) that has been evaluated and shown to effect asthma self
      management in children is used to exemplify the application of theory to
      practice. Impact and outcome evaluation studies have indicated the effectiveness
      of these steps in providing increased rigor and accountability, suggesting their
      utility for educators and developers seeking to apply simulations to enhance self
      management behaviors in patients.

PMID- 19088585
TI  - Crossing the line: simulation and boundary areas.

PMID- 19088586
TI  - Patient safety, competency, and the future of surgical simulation.
AB  - Despite its relatively short track record, simulation has been successfully
      introduced into the surgical arena in an effort to augment training. Initially a
      fringe endeavor at isolated centers, simulation has now become a mainstream
      component of surgical education. The surgical community is now aware that the old
      adage, "see one, do one, and teach one" is no longer acceptable from the ethical
      standpoint of practicing procedures on patients. Moreover, financial and time
      constraints have made teaching outside of the operating room an attractive
      proposition. Coupled with the growing body of validation, new procedures can now
      be practiced and proficiency can be acquired on a multitude of simulation
      platforms. Importantly, simulation standards are being established and there is
      an unprecedented national acceptance and endorsement of simulation as an
      invaluable educational tool; in fact, simulation is being mandated for surgical
      residency programs. Team training will likely expand the impact of surgical
      simulation considerably and help assure multidimensional competency verification.
      For both surgery residents and surgeons in practice, simulation holds great
      promise as a safe, effective, and efficient means of acquiring new skills.

PMID- 19088587
TI  - Consensus guidelines for validation of virtual reality surgical simulators.
AB  - The Work Group for Evaluation and Implementation of Simulators and Skills
      Training Programmes is a newly formed subgroup of the European Association of
      Endoscopic Surgeons (EAES). This work group undertook a review of validation
      evidence for surgical simulators and the resulting consensus is presented in this
      article. Using clinical guidelines criteria, the evidence for validation for 6
      different simulators was rated and subsequently translated to a level of
      recommendation for each system. The simulators could be divided into 2 basic
      types; systems for laparoscopic general surgery and flexible gastrointestinal
      endoscopy. Selection of simulators for inclusion in this consensus was based on
      their availability and relatively widespread usage as of July 2004. While level 2
      recommendations were achieved for a few systems, it was clear that there was an
      overall lack of published validation studies with rigorous experimental
      methodology. Since the consensus meeting, there have been a number of new
      articles, system upgrades and new devices available. The work group intends to
      update these consensus guidelines on a regular basis, with the resulting article
      available on the EAES website (http://www.eaes-eur.org).

PMID- 19088588
TI  - Comparision and Contrast between Police and Medical Simulation.

PMID- 19088589
TI  - An Introduction of Teaching Theory to HFPS Literature.

PMID- 19088590
TI  - The scope of simulation-based healthcare education.

PMID- 19088591
TI  - Effective management of anaesthetic crises: development and evaluation of a
      college-accredited simulation-based course for anaesthesia education in Australia
      and New Zealand.
AB  - The Effective Management of Anesthetic Crises (EMAC) course is a joint initiative
      between the Australian and New Zealand College of Anesthetists (ANZCA) and
      simulation centers. This standardized 2.5-day course has become an integral
      component of training for Fellowship of ANZCA and as such is an innovative
      development on the global anesthesia scene.Since its inception in 2002, over 600
      anesthetists, with equal numbers of specialists and trainees, have attended EMAC
      throughout Australia, New Zealand, and Hong Kong. Course evaluations from 499
      anesthetists and a follow-up survey showed strong support for the course and its
      relevance to clinical practice. The course is perceived by participants as
      changing their practice and improving their management of anesthetic
      crises.Exposure to the concepts of effective crisis management is now widespread
      in the anesthetic community in the region and should contribute to improved
      patient safety.

PMID- 19088592
TI  - How do clinical clerkship students experience simulator-based teaching? A
      qualitative analysis.
AB  - OBJECTIVES: To critically analyze the experience of clinical clerkship students
      exposed to simulator-based teaching, in order to better understand student
      perspectives on its utility. METHODS: A convenience sample of clinical students
      (n = 95) rotating through an emergency medicine, surgery, or longitudinal patient
      doctor clerkship voluntarily participated in a 2-hour simulator-based teaching
      session. Groups of 3-5 students managed acute scenarios including respiratory
      failure, myocardial infarction, or multisystem trauma. After the session,
      students completed a brief written evaluation asking for free text commentary on
      the strengths and weaknesses of the experience; they also provided simple
      satisfaction ratings. Using a qualitative research approach, the textual
      commentary was transcribed and parsed into fragments, coded for emergent themes,
      and tested for inter-rater agreement. RESULTS: Six major thematic categories
      emerged from the qualitative analysis: The "Knowledge & Curriculum" domain was
      described by 35% of respondents, who commented on the opportunity for self
      assessment, recall and memory, basic and clinical science learning, and
      motivation. "Applied Cognition and Critical Thought" was highlighted by 53% of
      respondents, who commented on the value of decision-making, active thought,
      clinical integration, and the uniqueness of learning-by-doing. "Teamwork and
      Communication" and "Procedural/Hands-On Skills" were each mentioned by 12% of
      subjects. Observations on the "Teaching/Learning Environment" were offered by 80%
      of students, who commented on the realism, interactivity, safety, and
      emotionality of the experience; here they also offered feedback on format,
      logistics, and instructors. Finally, "Suggestions for Use/Place in Undergraduate
      Medical Education" were provided by 22% of subjects, who primarily recommended
      more exposure. On a simple rating scale, 94% of students rated the quality of the
      simulator session as "excellent," whereas 91% felt the exercises should be
      "mandatory." CONCLUSION: Full-body simulation promises to address a wide range of
      pedagogical objectives using a unified educational platform. Students value
      experiential "practice without risk" and want more exposure to simulation. In
      this study, students thought that that an integrated simulation exercise could
      help solidify knowledge across domains, foster critical thought and action,
      enhance technical-procedural skills, and promote effective teamwork and
      communication.

PMID- 19088593
TI  - Simulating extracorporeal membrane oxygenation emergencies to improve human
      performance. Part I: methodologic and technologic innovations.
AB  - BACKGROUND: Extracorporeal membrane oxygenation (ECMO) is a form of long-term
      cardiopulmonary bypass used to treat infants, children, and adults with
      respiratory and/or cardiac failure despite maximal medical therapy. Mechanical
      emergencies on extracorporeal membrane oxygenation (ECMO) have an associated
      mortality of 25%. Thus, acquiring and maintaining the technical, behavioral, and
      critical thinking skills necessary to manage ECMO emergencies is essential to
      patient survival. Traditional training in ECMO management is primarily didactic
      in nature and usually complemented with varying degrees of hands-on training
      using a water-filled ECMO circuit. These traditional training methods do not
      provide an opportunity for trainees to recognize and interpret real-time clinical
      cues generated by human patients and their monitoring equipment. Adult learners
      are most likely to acquire such skills in an active learning environment. To
      provide authentic, intensive, interactive ECMO training without risk to real
      patients, we used methodologies pioneered by the aerospace industry and our
      experience developing a simulation-based training program in neonatal
      resuscitation to develop a similar simulation-based training program in ECMO
      crisis management, ECMO Sim. METHODS: A survey was conducted at the 19th Annual
      Children's National Medical Center ECMO Symposium to determine current methods
      for ECMO training. Using commercially available technology, we linked a neonatal
      manikin with a standard neonatal ECMO circuit primed with artificial blood. Both
      the manikin and circuit were placed in a simulated neonatal intensive care unit
      environment equipped with remotely controlled monitors, real medical equipment
      and human colleagues. Twenty-five healthcare professionals, all of whom care for
      patients on ECMO and who underwent traditional ECMO training in the prior year,
      participated in a series of simulated ECMO emergencies. At the conclusion of the
      program, subjects completed a questionnaire qualitatively comparing ECMO Sim with
      their previous traditional ECMO training experience. The amount of time spent
      engaged in active and passive activities during both ECMO Sim and traditional
      ECMO training was quantified by review of videotape of each program. RESULTS:
      Hospitals currently use lectures, multiple-choice exams, water drills, and animal
      laboratory testing for their ECMO training. Modification of the circuit allowed
      for physiologically appropriate circuit pressures (both pre- and postoxygenator)
      to be achieved while circulating artificial blood continuously through the
      circuit and manikin. Realistic changes in vital signs on the bedside monitor and
      fluctuations in the mixed venous oxygen saturation monitor were also effectively
      achieved remotely. All subjects rated the realism of the scenarios as good or
      excellent and described ECMO Sim as more effective than traditional ECMO
      training. They reported that ECMO Sim engaged their intellect to a greater degree
      and better developed their technical, behavioral, and critical thinking skills.
      Active learning (eg, hands-on activities) comprised 78% of the total ECMO Sim
      program compared with 14% for traditional ECMO training (P < 0.001). Instructor
      led lectures predominated in traditional ECMO training. CONCLUSION: Traditional
      ECMO training programs have yet to incorporate simulation-based methodology.
      Using current technology it is possible to realistically simulate in real-time
      the clinical cues (visual, auditory, and tactile) generated by a patient on ECMO.
      ECMO Sim as a training program provides more opportunities for active learning
      than traditional training programs in ECMO management and is overwhelmingly
      preferred by the experienced healthcare professionals serving as subjects in this
      study. Subjects also indicated that they felt that the acquisition of key
      cognitive, technical, and behavioral skills and transfer of those skills to the
      real medical domain was better achieved during simulation-based training.

PMID- 19088594
TI  - Simulating extracorporeal membrane oxygenation emergencies to improve human
      performance. Part II: assessment of technical and behavioral skills.
AB  - BACKGROUND: Healthcare professionals are expected to make rapid, correct
      decisions in critical situations despite what may be a lack of real practical
      experience in a particular crisis situation. Successful resolution of a medical
      crisis depends upon demonstration not only of appropriate technical skills but
      also of key behavioral skills (eg, leadership, communication, and teamwork). We
      have developed a hands-on, high fidelity, simulation-based training program (ECMO
      Sim) to provide healthcare professionals with the opportunity to learn and
      practice the technical and behavioral skills necessary to manage ECMO
      emergencies. METHODS: Nine ECMO nurse specialists participated in two sequential
      randomly assigned simulated ECMO emergencies. The simulated emergencies were
      captured on videotape and reviewed with the subjects during facilitated
      debriefings that occurred immediately following each scenario. All videotapes
      were scored for key technical and behavioral skills by reviewers blinded to the
      sequence of the scenarios. The ratings of the subjects' technical and behavioral
      skills in each scenario were compared. RESULTS: Subjects performed key technical
      skills correctly more often in the second simulated ECMO emergency. In addition,
      their response times for three out of five specific technical tasks improved from
      the first to the second simulated emergency by an average of 27 seconds.
      Subjects' behavioral skills were rated more highly by masked reviewers in the
      second simulated ECMO emergency. The improvement in comprehensive behavioral
      scores from the first to the second scenario reached statistical significance in
      eight of nine subjects. CONCLUSION: After exposure to high-fidelity simulated
      ECMO emergencies, subjects demonstrated significant improvements in their
      technical and behavioral skills. ECMO Sim creates a learning environment that
      readily supports the acquisition of the technical and behavioral skills that are
      important in solving clinically significant, potentially life-threatening
      problems that can occur when patients are on ECMO.

PMID- 19088596
TI  - Democratization of medical knowledge and technology: brief commentary on
      implications for medical education.
AB  - Today's movement towards the democratization of knowledge and dissemination of
      technology creates an opportunity for health care providers to reform medical
      education, bridge disciplines, and contribute to the correction of social
      inequalities. The question is whether this generation of physicians will have the
      courage to bring down the barriers that have deprived the majority of humanity
      from the medical knowledge, technology, and healthcare that rightfully belongs to
      all.

PMID- 19088595
TI  - Michael S. Gordon, MD, PhD and the University of Miami Center for Research in
      Medical Education.

PMID- 19088597
TI  - Trauma and awareness.

PMID- 19088599
TI  - Simulation-based medical education: an ethical imperative.
AB  - Medical training must at some point use live patients to hone the skills of
      health professionals. But there is also an obligation to provide optimal
      treatment and to ensure patients' safety and well-being. Balancing these 2 needs
      represents a fundamental ethical tension in medical education. Simulation-based
      learning can help mitigate this tension by developing health professionals'
      knowledge, skills, and attitudes while protecting patients from unnecessary risk.
      Simulation-based training has been institutionalized in other high-hazard
      professions, such as aviation, nuclear power, and the military, to maximize
      training safety and minimize risk. Health care has lagged behind in simulation
      applications for a number of reasons, including cost, lack of rigorous proof of
      effect, and resistance to change. Recently, the international patient safety
      movement and the U.S. federal policy agenda have created a receptive atmosphere
      for expanding the use of simulators in medical training, stressing the ethical
      imperative to "first do no harm" in the face of validated, large epidemiological
      studies describing unacceptable preventable injuries to patients as a result of
      medical management. Four themes provide a framework for an ethical analysis of
      simulation-based medical education: best standards of care and training, error
      management and patient safety, patient autonomy, and social justice and resource
      allocation. These themes are examined from the perspectives of patients,
      learners, educators, and society. The use of simulation wherever feasible conveys
      a critical educational and ethical message to all: patients are to be protected
      whenever possible and they are not commodities to be used as conveniences of
      training.

PMID- 19088598
TI  - Venous air embolism during sitting craniotomy.

PMID- 19088600
TI  - Using clinical outcomes data to reform medical education.

PMID- 19088601
TI  - The tide is turning: organizational structures to embed simulation in the fabric
      of healthcare.

PMID- 19088602
TI  - The mayo high performance teamwork scale: reliability and validity for evaluating
      key crew resource management skills.
AB  - PURPOSE: To develop and evaluate a participant rating scale for assessing high
      performance teamwork skills in simulation medicine settings. METHODS: In all, 107
      participants in crisis resource management (CRM) training in a multidisciplinary
      medical simulation center generated 273 ratings of key CRM skills after
      participating in two or three simulation exercises. These data were analyzed
      using Rasch and traditional psychometric approaches to develop the 16-item Mayo
      High Performance Teamwork Scale (MHPTS). Sensitivity to change as a result CRM
      training was also evaluated. RESULTS: The MHPTS showed satisfactory internal
      consistency and construct validity by Rasch (person reliability = 0.77; person
      separation = 1.85; item reliability = 0.96; item separation = 5.04) and
      traditional psychometric (Cronbach's alpha = 0.85) indicators. The scale
      demonstrated sensitivity to change as a result of CRM training (pretraining mean
      = 21.44 versus first posttraining rating mean = 24.37; paired t = -4.15, P <
      0.0001; first posttraining mean = 24.63 versus second posttraining mean = 26.83;
      paired t = -4.31 P < 0.0001). CONCLUSIONS: The MHPTS provides a brief, reliable,
      practical measure of CRM skills that can be used by participants in CRM training
      to reflect on and evaluate their performance as a team. Further evaluation of
      validity and appropriateness in other simulation and medical settings is
      desirable.

PMID- 19088603
TI  - A simulation course on lifesaving techniques for third-year medical students.
AB  - BACKGROUND: The University of Virginia School of Medicine discontinued animal
      vivisection in February 2004 for teaching lifesaving procedures to third-year
      medical students. Consequently, a 1-day course using simulation technology was
      developed to meet objectives previously covered in the animal laboratory. The
      authors sought to evaluate the course and hypothesized that the students'
      confidence in lifesaving procedures as well as their acceptance of simulation
      technology as a teaching tool would increase. METHODS: The course was designed in
      a two-session format. The first session (first half of the day) concentrated on
      individual procedure skills, utilizing part-task trainers. The second session
      (second half of the day) used a Medical Education Technologies Inc. (METI)
      Emergency Care Simulator (ECS) full-body patient simulator to present a major
      trauma scenario. The study design was a prospective, pretest-posttest study
      without a control group. A 10-question pre and post survey used a Likert scale to
      explore students' confidence in their skills as well as their acceptance of
      simulation technology. A course evaluation used a similar Likert scale for
      evaluation of the course substations, the trauma scenario, and students' self
      assessment of their skill levels as well as a 100% point scale for an overall
      rating of the course. RESULTS: A total of eight 1-day courses were successfully
      held over 2 years with a total enrollment of 240 students utilizing 20
      instructors inclusive of faculty, residents, and other emergency medicine health
      care providers. For the pre and post survey results, there was a significant
      increase in students' confidence in performing lifesaving procedures as well as
      their acceptance of simulation as a teaching tool (P < 0.05 for each question
      with pre n = 222 and post n = 226). For the course evaluation results (n = 190),
      all of the course substations were rated in the good to excellent range and the
      course received an overall score of 97.55 +/- 7.23% out of 100%. Furthermore,
      students reported a significant increase in their skill level (P < 0.05).
      CONCLUSION: This lifesaving techniques course utilizing simulation technology
      successfully covered objectives previously taught with animal vivisection,
      increased students' confidence levels in performing lifesaving procedures and was
      highly accepted by the medical students.

PMID- 19088604
TI  - Enhancing graduate nurses' health assessment knowledge and skills using low
      fidelity adult human simulation.
AB  - PURPOSE: Although simulation technology in nursing education is becoming
      increasingly commonplace, a review of the literature reveals a paucity of
      rigorous, high-level research comparing the effectiveness of simulation with
      other traditional education methods in the acquisition of clinical knowledge and
      skills. This research aimed to investigate the impact of three learning
      interventions on graduate nurse health assessment knowledge and skills. It was
      hypothesized that the patient assessment skills of graduate nurses who completed
      a simulation learning activity would be superior to those who completed
      traditional education activities. METHODS: Graduate nurses (n = 74) were randomly
      allocated to three groups (1: self-directed learning package [SDLP] only; 2: SDLP
      plus two scenario-based PowerPoint workshops; and 3: SDLP plus two simulation
      education sessions using a manikin with low-fidelity capabilities. Following the
      education activities, graduates completed an individual test involving a
      systematic patient assessment upon a manikin. They were scored using a checklist
      of relevant responses. RESULTS: Analysis of variance results suggest that the
      mean test score for nurses in the simulation group (mean = 135.52, SD = 26.63)
      was significantly higher (P < 0.001) than those in the learning package group
      (mean = 107.42, SD = 29.82) and the PowerPoint group (mean = 102.77, SD = 31.68).
      CONCLUSIONS: Simulation appears to be an effective educational tool for teaching
      patient assessment knowledge and skills to graduate nurses. Incorporation of such
      technology into graduate nurse education may decrease the time required to become
      clinically proficient, resulting in more confident and work-ready practitioners.

PMID- 19088605
TI  - An innovative and inexpensive model for teaching cricothyrotomy.
AB  - Cricothyrotomy is considered an integral procedure in the practice of emergency
      medicine. The Accreditation Council for Graduate Medical Education requires
      residents in emergency medicine to demonstrate proficiency in this skill, but
      because cricothyrotomy is rarely encountered in the clinical setting, alternative
      methods to teach this high-stakes procedure become an important curricular
      component in residency training. We present an innovative and inexpensive method
      for teaching cricothyrotomy using animal trachea and synthetic skin.

PMID- 19088606
TI  - The complementary roles of the advanced initiative in medical simulation and the
      society for simulation in healthcare.

PMID- 19088607
TI  - 2006 simulation summit.
AB  - In November 2006, a Simulation Summit was convened in Chicago, IL by the Society
      for Simulation in Healthcare. The purpose of this gathering was to bring together
      stakeholders from the widest possible range of societies, organizations, and
      regulatory agencies with an interest in healthcare simulation. Thirty-three
      organizations were represented by over 50 participants. Through structured small
      and large group discussions, eight major themes emerged for the advancement of
      simulation into the mainstream of healthcare education. Four of these were
      unanimously agreed upon, and four were widely accepted by the group. This paper
      summarizes the results of this Summit including future plans to advance the
      integration of simulation into the mainstream of healthcare.

PMID- 19088608
TI  - Intraoperative apnea: medication error with disclosure (simulation case
      scenario).

PMID- 19088609
TI  - Stanford university medical media and information technologies hosts open source
      surgical simulation workshop.
AB  - Stanford University Medical Media and Information Technologies's technical
      workshop "Prototyping of Surgical Simulators using Open Source Simulation
      Software" was held in August 2006 at Stanford University. The objectives,
      program, and topics covered are presented in this short report.

PMID- 19088611
TI  - When the editor is an author.

PMID- 19088610
TI  - Simulation: an agenda for the 21st century.

PMID- 19088612
TI  - Millennium conference 2005 on medical simulation: a summary report.
AB  - INTRODUCTION: Medical simulation takes advantage of contextual and experiential
      learning by allowing trainees to practice in realistic environments prior to
      actual patient care. Although proponents argue that patient simulation can
      fundamentally enhance both medical education and patient safety, large-scale
      experience with advanced simulation technologies is limited. To explore expert
      opinion on the topic, we convened a conference of educational leaders and
      simulation experts to provide recommendations for how this field should be
      directed on a broad scale to improve the training of future health professionals.
      This document summarizes the proceedings of that conference. METHODS: We issued a
      request for applications to all U.S. and Canadian medical schools within the
      Association of American Medical Colleges (AAMC), seeking a diverse group of
      institutional teams committed to an in-depth exploration of the topic. Of 33
      applications, nine medical schools were selected to participate. Once on site,
      eight working groups were formed, each comprised of representatives across sites
      and roles, including deans, clerkship and program directors, content experts, and
      trainees. We addressed four key topics, which are subsequently summarized for
      presentation in this report: 1) education (How can medical simulation contribute
      to the education of trainees?), 2) assessment (What is the role of simulation in
      evaluating trainees in the context of general competencies?), 3) research (How
      should we develop a research agenda to evaluate simulation?), and 4)
      implementation (How should simulation technologies be developed and managed
      within and across institutions?). RESULTS: Participants in the conference
      generally agreed that simulation offers a conducive environment for focused
      reflection and critical thought. Although there was consensus that medical
      simulation can provide a robust platform for performance assessment, most
      participants thought that the research basis for high-stakes assessment was still
      too immature for widespread implementation. Participants generally agreed that
      sufficiently powered research will require interinstitutional collaboration on
      uniform curricula and meaningful outcome tools, and that both biomedical and
      social science research paradigms will need to be applied to the questions at
      hand. Common barriers to medical simulation include both real and perceived lack
      of resources, poor understanding among faculty regarding the nature of the tools
      and techniques, and the inherent complexity of multidisciplinary collaboration.
      CONCLUSIONS: Medical simulation can and should be used to complement current
      methods of medical education. Educators should make thoughtful choices among
      simulation modalities to help trainees most effectively achieve learning
      objectives. Simulation researchers should prioritize the development and
      validation of clinical performance tools and other defined outcome measures on
      which meaningful large-scale research can be anchored. Finally, national
      collaboration should be encouraged and fostered by institutions and funding
      agencies.

PMID- 19088613
TI  - Crisis resource management: evaluating outcomes of a multidisciplinary team.
AB  - Crisis resource management (CRM) is a team-training program that teaches
      nontechnical skills such as: collaboration, communication, task management,
      teamwork, and leadership. The purpose of this study was to evaluate improvement
      in the nontechnical skills of a multidisciplinary team of pediatric residents,
      anesthesiology residents and pediatric nurses following participation in the CRM
      educational program. Self-efficacy theory guided the teaching method used in the
      CRM program. The Collaboration and Satisfaction about Care Decisions instrument
      and the Anesthetists' Nontechnical Skills System served as outcome measures.
      Seven multidisciplinary groups were studied with a total of 40 subjects. A
      significant increase was found in posttest scores for perceived collaboration and
      satisfaction with care and in numerical ratings of observed team skills following
      the CRM program. The results suggest multidisciplinary team participation in the
      CRM program increased perceived team collaboration, satisfaction with care, and
      observed teamwork skills.

PMID- 19088614
TI  - A method for designing symmetrical simulation scenarios for evaluation of
      behavioral skills.

PMID- 19088615
TI  - The effects of human patient simulators on basic knowledge in critical care
      nursing with undergraduate senior baccalaureate nursing students.
AB  - BACKGROUND: The nursing literature to date has offered many descriptive accounts
      utilizing human simulation in undergraduate and graduate nursing curricula.
      However, the nursing literature remains sparse in the area of studies that
      evaluate the effectiveness of simulation on knowledge attainment in critical care
      using standardized assessment tools. The primary aim of this paper is to report
      on a study that investigates whether participation in instruction involving human
      patient simulators, in conjunction with a traditional clinical experience,
      improves professional competence in senior-level undergraduate nursing students
      related to basic knowledge of critical care nursing. METHODS: This study (n=29)
      used a pre- and posttest repeated-measure design. Senior baccalaureate nursing
      students enrolled in an advanced medical-surgical nursing course participated.
      Students were assigned to groups and completed 7 weeks of traditional clinical
      experience (45 hours total) and 7 weeks of high-fidelity human simulation (45
      hours total). Students completed the Basic Knowledge Assessment Tool-6 (BKAT-6)
      prior to traditional clinical and on the last day of human simulation experience.
      RESULTS: Results showed a significant improvement on the BKAT-6 overall and a
      significant improvement in 6 subscales of the BKAT-6. CONCLUSION: Instruction
      involving high-fidelity human simulation is a viable teaching strategy to improve
      basic knowledge acquisition as one essential attribute needed for professional
      competence.

PMID- 19088616
TI  - The role of debriefing in simulation-based learning.

PMID- 19088617
TI  - The future vision of simulation in healthcare.
AB  - Simulation is a technique-not a technology-to replace or amplify real experiences
      with guided experiences that evoke or replicate substantial aspects of the real
      world in a fully interactive manner. The diverse applications of simulation in
      healthcare can be categorized by 11 dimensions: aims and purposes of the
      simulation activity; unit of participation; experience level of participants;
      healthcare domain; professional discipline of participants; type of knowledge,
      skill, attitudes, or behaviors addressed; the simulated patient's age; technology
      applicable or required; site of simulation; extent of direct participation; and
      method of feedback used. Using simulation to improve safety will require full
      integration of its applications into the routine structures and practices of
      healthcare. The costs and benefits of simulation are difficult to determine,
      especially for the most challenging applications, where long-term use may be
      required. Various driving forces and implementation mechanisms can be expected to
      propel simulation forward, including professional societies, liability insurers,
      healthcare payers, and ultimately the public. The future of simulation in
      healthcare depends on the commitment and ingenuity of the healthcare simulation
      community to see that improved patient safety using this tool becomes a reality.

PMID- 19088618
TI  - Which reality matters? Questions on the path to high engagement in healthcare
      simulation.

PMID- 19088620
TI  - Comparison of self-directed learning versus instructor-modeled learning during a
      simulated clinical experience.
AB  - BACKGROUND: There are no reports in the literature that compare instructor
      modeled learning to self-directed learning when simulation is used. Therefore, no
      evidence exists to know which approach is superior. This study aims to test the
      hypothesis that instructor-modeled learning is more effective compared with self
      directed learning during a simulated clinical experience. METHODS: This is a
      descriptive pilot study to compare instructor-modeled learning with self-directed
      learning during a clinical simulated experience. Four evaluation tools were used
      at three time points to evaluate knowledge, self-efficacy (self confidence), and
      behaviors. RESULTS: Sixteen students participated. There were no statistically
      significant differences between the groups on the Knowledge Assessment Test.
      There were significant differences between the groups in the Self-Efficacy Tool
      (SET) at three times (time 1: P = 0.006, time 2: P = 0.008, time 3: P = 0.012).
      The only significance between the groups on the Technical Evaluation Tool was
      time to start Albuterol. The Behavioral Assessment Tool (BAT) showed significant
      differences between the groups in 8 out of 10 components of the tool. A strong
      correlation was observed between the overall score of the BAT and the SET Score.
      CONCLUSION: Although the small sample size prohibits definitive conclusions, the
      data suggest that instructor-modeled learning may be more effective than self
      directed learning for some aspects of learning during a clinical simulated
      experience.

PMID- 19088619
TI  - A randomized trial of simulation-based versus conventional training of dental
      student skill at interpreting spatial information in radiographs.
AB  - INTRODUCTION: A radiology simulator has been developed. We tested the simulator
      with students in an oral radiology program for training interpretation of spatial
      relations in radiographs utilizing parallax. The aim of the study was to compare
      learning outcome regarding interpretative skill after training in the simulator
      vs. after conventional training. METHODS: Fifty-seven dental students voluntarily
      participated in a randomized experimental study. The participants' proficiency in
      interpretation of spatial information in radiographs and their visual-spatial
      ability was assessed. Proficiency was assessed by a test instrument designed by
      the authors and visual-spatial ability with the Mental Rotations Test, version A
      (MRT-A). Randomization to training group was based on pre-training proficiency
      test results. The experimental group trained in the simulator and the control
      group received conventional training. Training lasted for 90 minutes for both
      groups. Immediately after training a second proficiency test was performed.
      RESULTS: The proficiency test results were significantly higher after training
      for the experimental group (P < or = 0.01), but not for the control group.
      Univariate variance analysis of difference in proficiency test score revealed a
      significant interaction effect (P = 0.03) between training group and MRT-A
      category; in the experimental group there was a stronger training effect among
      students with low level of MRT-A. CONCLUSIONS: Training in the simulator improved
      skill in interpreting spatial information in radiographs when evaluated
      immediately after training. For individuals with low visual-spatial ability
      simulator based training seems to be more beneficial than conventional training.

PMID- 19088621
TI  - Construct validation of a laparoscopic surgical simulator.
AB  - BACKGROUND: Laparoscopic simulators are increasingly used to train and evaluate
      surgical skill, and validating laparoscopic simulators for these purposes is
      paramount. Our goal was to determine if the SurgicalSIM laparoscopic surgical
      simulator can discriminate between novices and experts and to assess learning
      curves among novices. METHODS: Twenty novices and five experts performed five
      repetitions on the following modules: place arrow, retract, dissect, and traverse
      tube. For each module, median baseline performance was calculated. Novices
      performed 35 additional repetitions to assess learning with practice. RESULTS:
      Experts outperformed novices at baseline for time to completion on the dissect,
      place arrow, and traverse tube modules, as well as for error frequency on the
      traverse tube and retract modules. Novices' performance improved significantly
      with practice, approaching the experts' baseline in all modules. CONCLUSION: The
      SurgicalSIM laparoscopic simulator exhibits construct validity on three of four
      basic-skills modules when considering completion time and on two modules when
      considering error frequency. Among novices, learning occurred with additional
      repetitions. Whether acquired skills transfer to the actual surgical environment
      has yet to be determined.

PMID- 19088622
TI  - Deepening the theoretical foundations of patient simulation as social practice.
AB  - Simulation is a complex social endeavor, in which human beings interact with each
      other, a simulator, and other technical devices. The goal-oriented use for
      education, training, and research depends on an improved conceptual clarity about
      simulation realism and related terms. The article introduces concepts into
      medical simulation that help to clarify potential problems during simulation and
      foster its goal-oriented use. The three modes of thinking about reality by Uwe
      Laucken help in differentiating different aspects of simulation realism
      (physical, semantical, phenomenal). Erving Goffman's concepts of primary frames
      and modulations allow for analyzing relationships between clinical cases and
      simulation scenarios. The as-if concept by Hans Vaihinger further qualifies the
      differences between both clinical and simulators settings and what is important
      when helping participants engage in simulation. These concepts help to take the
      social character of simulation into account when designing and conducting
      scenarios. The concepts allow for improved matching of simulation realism with
      desired outcomes. It is not uniformly the case that more (physical) realism means
      better attainment of educational goals. Although the article concentrates on
      mannequin-based simulations that try to recreate clinical cases to address issues
      of crisis resource management, the concepts also apply or can be adapted to other
      forms of immersive or simulation techniques.

PMID- 19088623
TI  - Scenario and checklist for airway rescue during pediatric sedation.

PMID- 19088624
TI  - Out of this nettle, danger, we pluck this flower, safety: healthcare vs. aviation
      and other high-hazard industries.

PMID- 19088625
TI  - Mannequin-based simulation to reinforce pharmacology concepts.
AB  - Simulation education provides many new learning opportunities to healthcare
      training. This article delineates a method that utilizes a variety of teaching
      methods that include structured lecture-based education, active simulation-based
      education, and reflective inquiry. A course in pharmacology is used as an example
      to show how these different methods can be employed to offer students an
      immersive experience that reinforces traditional lecture-based learning. The
      paper is presented in such a way that it is easily applied to multiple situations
      and includes schematics, evaluation data, and equipment lists. Evaluation data
      strongly supported the continued use of this methodology.

PMID- 19088626
TI  - High fidelity, high performance?
AB  - Developers of medical simulators and instructors who use them often have
      questions about the level of fidelity needed in a simulation. In this article, we
      address the nature of fidelity with respect to virtual reality training systems.
      We argue that high-fidelity simulators do not always lead to better performance,
      and in some instances, can interfere with performance. The primary reason for
      these seemingly counterintuitive findings lies with a fundamental understanding
      of how humans perceive and process sensory information. Consequently, simulation
      based training systems should be developed to maximize their effectiveness, not
      their fidelity.

PMID- 19088627
TI  - Endotracheal intubation: application of virtual reality to emergency medical
      services education.
AB  - Virtual reality simulation has been identified as an emerging educational tool
      with significant potential to enhance teaching of residents and students in
      emergency clinical encounters and procedures. Endotracheal intubation represents
      a critical procedure for emergency care providers. Current methods of training
      include working with cadavers and mannequins, which have limitations in their
      representation of reality, ethical concerns, and overall availability with
      access, cost, and location of models. This paper will present a human airway
      simulation model designed for tracheal intubation and discuss the aspects that
      lend itself to use as an educational tool. This realistic and dynamic model is
      used to teach routine intubations, while future models will include more
      difficult airway management scenarios. This work provides a solid foundation for
      future versions of the intubation simulator, which will incorporate two haptic
      devices to allow for simultaneous control of the laryngoscope blade and
      endotracheal tube.

PMID- 19088628
TI  - Shock in a pediatric patient: an electrical diagnosis.

PMID- 19088629
TI  - Keep it flowing: a simulation involving defective anesthetic gas delivery
      equipment.

PMID- 19088630
TI  - Designing case-based learning for virtual worlds.

PMID- 19088631
TI  - Abstracts of the 7th Annual International Meeting on Simulation in Healthcare.
      January 14-17,2007. Lake Buena Vista, Florida, USA.

PMID- 19088635
TI  - Team performance assessment in healthcare: facing the challenge.

PMID- 19088636
TI  - Recognition and treatment of unstable supraventricular tachycardia by pediatric
      residents in a simulation scenario.
AB  - INTRODUCTION: Supraventricular tachycardia (SVT) is the most frequent
      tachydysrhythmia in children. SVT with hemodynamic compromise should be
      terminated by immediate electrical cardioversion. Study objectives were to: (1)
      establish time to recognition and cardioversion of simulated unstable SVT; and
      (2) document delays and mistakes made during cardioversion. METHODS: Ten teams of
      pediatric residents were presented with an unresponsive "patient" (Laerdal
      SimMan) in unstable SVT. Actions of team members and simulator timestamps of key
      events were recorded. A retrospective review of events and time logs was
      performed with primary outcome measure of time to successful cardioversion.
      RESULTS: Median time to cardioversion was 8.9 minutes (range, 5.3 minutes to
      unsuccessful scenario terminated at 15 minutes). In 20% of scenarios, the patient
      was never cardioverted. Ninety percent of teams administered adenosine, but 44%
      of attempts demonstrated incorrect administration technique. Other maneuvers
      before cardioversion: 70% administered fluid, 60% attempted vagal maneuvers, 30%
      requested electrocardiogram, 30% requested antiarrhythmics. In 20% of scenarios,
      the rhythm was misidentified. When cardioversion was performed, 25% failed to use
      gel, 37.5% failed to synchronize, 25% used inappropriate energy doses. In 60% of
      scenarios, no oxygen was administered. In 90% there was no assignment of Glasgow
      Coma Scale, and no assessment of mental status in 30%. In 60% perfusion was not
      assessed. CONCLUSIONS: Median time to cardioversion of 8.9 minutes is
      inconsistent with AHA recommendations for treatment of unstable SVT with
      "immediate cardioversion." Delays were secondary to lack of recognition of
      "unstable" SVT, due to failure to assess perfusion and mental status. Errors
      encountered during simulation identify curriculum reform targets.

PMID- 19088638
TI  - LapMentor metrics possess limited construct validity.
AB  - BACKGROUND: Many surgical training programs are introducing virtual-reality
      laparoscopic simulators into their curriculum. If a surgical simulator will be
      used to determine when a trainee has reached an "expert" level of performance,
      its evaluation metrics must accurately reflect varying levels of skill. The
      ability of a metric to differentiate novice from expert performance is referred
      to as construct validity. The present study was undertaken to determine whether
      the LapMentor's metrics demonstrate construct validity. METHODS: Medical
      students, residents and faculty laparoscopic surgeons (n = 5-14 per group)
      performed 5 consecutive repetitions of 6 laparoscopic skills tasks: 30 degrees
      Camera Manipulation, Eye-Hand Coordination, Clipping/Grasping, Cutting,
      Electrocautery, and Translocation of Objects. The LapMentor measured performance
      in 4 to 12 parameters per task. Mean performance for each parameter was compared
      between subject groups for the first and fifth repetitions. Pairwise comparisons
      among the 3 groups were made by post hoc t-tests with Bonferroni technique.
      Significance was set at P < 0.05. RESULTS: Of the 6 tasks evaluated, only the Eye
      Hand Coordination task (3/12 parameters) and the Clipping and Grasping (1/7
      parameters) had expert-level discrimination when performance was compared after
      completion of 1 repetition. Comparison of the fifth repetition performance
      (representing the plateau of the learning curves), demonstrated that the
      parameters Time and Score had expert level discrimination on the Eye-Hand
      Coordination task, and Time on the Cutting task. The remaining LapMentor tasks
      evaluated did not exhibit the ability to differentiate level of expertise based
      on the built-in metrics on either repetition 1 or 5. CONCLUSIONS: The majority of
      the LapMentor tasks' metrics were unable to differentiate between laparoscopic
      experts and less skilled subjects. Therefore, performance on those tasks may not
      accurately reflect a subject's true level of ability. Feedback to the
      manufacturer about these findings may encourage the development of evaluation
      parameters with greater sensitivity.

PMID- 19088637
TI  - Medical students learn over distance using virtual reality simulation.
AB  - INTRODUCTION: This article presents the results of a demonstration project that
      was designed with the goal to determine the feasibility and acceptability of
      medical students in using distance technology and virtual reality (VR) simulation
      within a problem-based learning (PBL). METHODS: This pilot project involved
      students from the Universities of New Mexico and Hawaii and compared (1) control
      groups consisting of medical students in a tutor-guided PBL session using a text
      based case, (2) distance groups using the same text-based case but interacting
      over distance from multiple sites, (3) groups using a VR simulation scenario
      integrated into the case without interaction over distance, and (4) combination
      groups interacting over distance from multiple sites with integration of a VR
      simulation scenario. RESULTS: The study results suggest that it is possible to
      successfully conduct a PBL tutorial with medical students from two institutions
      with the integration VR and distributed distance interaction in combination or
      independently. The addition of these modalities did not interfere with learning
      dynamics when compared with traditional tutorial sessions. CONCLUSIONS: These
      findings suggest the feasibility and acceptability by students in the use of VR
      simulation integrated into a PBL learning session, as well as multipoint distance
      technologies that allowed interaction between students and tutors in different
      locations. The authors believe that these modalities can be applied where
      students and tutors from different institutions are in separate locations and can
      be used to support interactive experiential learning in a distributed network or
      on site and suggest areas for additional research.

PMID- 19088639
TI  - Understanding of anesthesia machine function is enhanced with a transparent
      reality simulation.
AB  - INTRODUCTION: Photorealistic simulations may provide efficient transfer of
      certain skills to the real system, but by being opaque may fail to encourage
      deeper learning of the structure and function of the system. Schematic
      simulations that are more abstract, with less visual fidelity but make system
      structure and function transparent, may enhance deeper learning and optimize
      retention and transfer of learning. We compared learning effectiveness of these 2
      modes of externalizing the output of a common simulation engine (the Virtual
      Anesthesia Machine, VAM) that models machine function and dynamics and responds
      in real time to user interventions such as changes in gas flow or ventilation.
      METHODS: Undergraduate students (n = 39) and medical students (n = 35) were given
      a single, 1-hour guided learning session with either a Transparent or an Opaque
      version of the VAM simulation. The following day, the learners' knowledge of
      machine components, function, and dynamics was tested. RESULTS: The Transparent
      VAM groups scored higher than the Opaque-VAM groups on a set of multiple-choice
      questions concerning conceptual knowledge about anesthesia machines (P = 0.009),
      provided better and more complete explanations of component function (P = 0.003),
      and were more accurate in remembering and inferring cause-and-effect dynamics of
      the machine and relations among components (P = 0.003). Although the medical
      students outperformed undergraduates on all measures, a similar pattern of
      benefits for the Transparent VAM was observed for these 2 groups. CONCLUSIONS:
      Schematic simulations that transparently allow learners to visualize, and
      explore, underlying system dynamics and relations among components may provide a
      more effective mental model for certain systems. This may lead to a deeper
      understanding of how the system works, and therefore, we believe, how to detect
      and respond to potentially adverse situations.

PMID- 19088640
TI  - Measuring team performance in simulation-based training: adopting best practices
      for healthcare.
AB  - Team performance measurement is a critical and frequently overlooked component of
      an effective simulation-based training system designed to build teamwork
      competencies. Quality team performance measurement is essential for
      systematically diagnosing team performance and subsequently making decisions
      concerning feedback and remediation. However, the complexities of team
      performance pose a challenge to effectively measuring team performance. This
      article synthesizes the scientific literature on this topic and provides a set of
      best practices for designing and implementing team performance measurement
      systems in simulation-based training.

PMID- 19088641
TI  - Development and use of mechanical devices for simulation of seizure and
      hemorrhage in obstetrical team training.
AB  - INTRODUCTION: The leading causes of pregnancy-related death are embolism (20%),
      hemorrhage (17%), and pregnancy-induced hypertension (16%).The Obstetric and
      Mechanical Engineering Departments at Stanford University worked together to
      create inexpensive devices that were used in high fidelity simulations to
      replicate 2 of the leading causes of maternal mortality: hemorrhage and eclampsia
      (seizure). METHODS: The mechanisms were designed to behave as similarly as
      possible to a human patient. The engineering team designed the eclampsia
      mechanism to jostle the mannequin's head at a frequency and randomness that
      matched those observed in human generalized seizures. The hemorrhage mechanism
      was designed to give visual and tactile cues similar to the actual physiology of
      a pregnant uterus. Both devices were remote controlled. RESULTS: The hemorrhage
      mechanism was used in a scenario of an amniotic fluid embolism with severe
      postpartum hemorrhage. The final flow rate was adjustable between 525 and 600
      mL/min. The trainees' rapid response and control of the postpartum hemorrhage was
      deemed to be a vital part of a successful maternal resuscitation. The seizure
      mechanism was used in a simulation of a pregnant woman in labor with evidence of
      severe preeclampsia. If the trainees did not recognize the need for treatment of
      the preeclampsia, the patient simulator had a 45- to 60-second seizure. If
      corrective actions were not taken, another seizure occurred. CONCLUSIONS: The use
      of remote controlled mechanical devices designed to accurately replicate the
      visual, auditory, and tactile cues of hemorrhage and eclampsia enhanced high
      fidelity simulation training in obstetrical emergencies.

PMID- 19088642
TI  - The patient simulator for training of anesthesia residents in the management of
      one lung ventilation.
AB  - Simulators are used extensively for the training of medical personnel. All
      anesthesia providers should be prepared and trained in the management of one lung
      ventilation for pulmonary surgery, yet familiarization with one lung ventilation
      may not be possible on a routine basis in the operating room. Therefore, this
      reports details the first use of the patient simulator (PS) to enhance the
      training of anesthesia residents in the management of one lung ventilation. A
      detailed report of our computer program for simulating one lung ventilation is
      included.

PMID- 19088643
TI  - Integrating simulation into a pediatric nursing curriculum: a 25% solution?

PMID- 19088644
TI  - Challenges and opportunities in simulation and assessment.

PMID- 19088645
TI  - Setting performance standards for mannequin-based acute-care scenarios: an
      examinee-centered approach.
AB  - BACKGROUND: In medicine, standard setting methodologies have been developed for
      both selected-response and performance-based assessments. For simulation-based
      tasks, research efforts have been directed primarily at assessments that
      incorporate standardized patients. Mannequin-based evaluations often demand
      complex, time-sensitive, hierarchically ordered, sequential actions that are
      difficult to evaluate and score. Moreover, collecting reliable proficiency
      judgments, necessary to estimate meaningful cut points, can be challenging. The
      purpose of this investigation was to explore whether expert judgments obtained
      using an examinee-centered standard setting method that was previously validated
      for standardized patient-based assessments could be used to set defensible
      standards for acute-care, mannequin-based scenarios. METHODS: Nineteen physicians
      were recruited to serve as panelists. For each of 12 simulation scenarios,
      between 8 and 10 performance samples (audio-video recordings), covering the
      expected ability continuum, were chosen for review. The performance samples were
      selected from a previously administered evaluation of postgraduate trainees.
      Based on a consensus definition of readiness to enter unsupervised practice, the
      panelists made independent judgments of each performance. For each scenario, the
      association between the panelists' judgments and the assessment scores was
      summarized and used to estimate a scenario-specific cut score. RESULTS: For 9 of
      the scenarios, there was at least a moderately strong relationship between the
      aggregate panelists' rating and the performance scores, thus allowing for
      estimation of meaningful numeric standards. For the other 3 scenarios, the
      aggregate decision rules used by the panelists did not correspond with the
      achievement measures. For scenarios independently rated by split panels, the
      estimated cut scores were similar. CONCLUSIONS: An examinee-centered approach,
      using aggregate expert judgments of audio-video performances, was suitable for
      setting standards on most acute-care, mannequin-based scenarios. It is necessary,
      however, to have valid scores for the chosen scenarios and to sample performances
      across the ability spectrum.

PMID- 19088646
TI  - OB/GYN boot cAMP using high-fidelity human simulators: enhancing residents'
      perceived competency, confidence in taking a leadership role, and stress
      hardiness.
AB  - OBJECTIVES: To evaluate the effectiveness of an obstetrical and gynecologic
      (Ob/Gyn) Boot Camp simulation training on perceived technical competency,
      confidence in a leadership role, and stress hardiness of resident training.
      METHODS: We conducted a prospective pilot study on the effectiveness of an Ob/Gyn
      Boot Camp on resident training. Residents participated in an intensive immersion
      in clinical simulation of common obstetrical emergencies including shoulder
      dystocia, neonatal resuscitation, postpartum hemorrhage, and ruptured ectopic
      pregnancy. After the training, residents completed a Web-based survey on their
      perceptions of how the Ob/Gyn Boot Camp affected their 1) technical competency in
      the assessment and management of their patients, 2) confidence in taking a
      leadership role, and 3) stress hardiness. Residents rated their perceptions on a
      Likert scale of 1 to 5, 1 = poor to 5 = excellent. RESULTS: Twenty-three (14
      Ob/Gyn and 9 family medicine) residents participated in this pilot study.
      Eighteen (78%) residents completed the online survey; 4 Ob/Gyn and 1 family
      medicine resident did not complete the survey. The residents reported that the
      simulation training stimulated an interest in learning key skills for obstetrical
      and gynecologic emergencies. Ob/Gyn residents reported significant improvement in
      their perceived technical competence and stress hardiness after the Boot Camp.
      However both Ob/Gyn and family medicine residents reported no significant
      improvement of confidence in their leadership abilities during obstetrical
      emergencies after the Boot Camp. CONCLUSION: Boot Camp simulation training early
      in the curriculum has the potential for enhancing residents' self-assessments of
      confidence, competency, and stress hardiness in managing obstetrical emergencies.

PMID- 19088647
TI  - Factors influencing nurses' attitudes toward simulation-based education.
AB  - OBJECTIVE: To identify barriers to nurses' participation in simulation, and to
      determine whether prior simulation exposure, professional experience, and
      practice location influence their tendency to perceive specific issues as
      barriers. We also sought to identify nurses' educational priorities, and to
      determine whether these were influenced by years of experience or practice
      location. METHODS: We surveyed full-time and part-time nurses in a university
      affiliated children's hospital to gather data on professional demographics,
      simulation exposure, perceived barriers to participation in simulation, and
      training priorities. RESULTS: A total of 523 of 936 (56%) eligible nurses
      completed the survey. Binary logistic regression analysis revealed that
      "simulation is 'not the real thing'" was selected as a barrier more often by
      nurses with prior simulation experience (P = 0.02), fewer years in practice (P =
      0.02), and employment in non-acute care areas of the hospital (P = 0.03).
      "Unfamiliarity with equipment" was reported more often by nurses with less
      experience (P = 0.01). "Stressful or intimidating environment" was selected more
      often by those who work in non-acute care areas (P < 0.01). "Providing
      opportunities to manage rare events" was suggested as a training priority by
      nurses with less experience (P = 0.08) and by those practicing in acute care
      areas (P = 0.03). CONCLUSIONS: We identified several barriers to nurses'
      participation in simulation training. Nurses' tendency to name specific issues as
      barriers is related to prior simulation exposure, years of experience, and area
      of hospital practice. Rehearsing rare event management is a priority for less
      experienced nurses and those in acute care areas.

PMID- 19088648
TI  - ProMIS augmented reality training of laparoscopic procedures face validity.
AB  - BACKGROUND: Conventional video trainers lack the ability to assess the trainee
      objectively, but offer modalities that are often missing in virtual reality
      simulation, such as realistic haptic feedback. The ProMIS augmented reality
      laparoscopic simulator retains the benefit of a traditional box trainer, by using
      original laparoscopic instruments and tactile tasks, but additionally generates
      objective measures of performance. METHODS: Fifty-five participants performed a
      "basic skills" and "suturing and knot-tying" task on ProMIS, after which they
      filled out a questionnaire regarding realism, haptics, and didactic value of the
      simulator, on a 5-point-Likert scale. The participants were allotted to 2
      experience groups: "experienced" (>50 procedures and >5 sutures; N = 27), and
      "moderately experienced" (<50 procedures and <5 sutures; N = 28). RESULTS:
      General consensus among all participants, particularly the experienced, was that
      ProMIS is a useful tool for training (mean: 4.67, SD: 0.48). It was considered
      very realistic (mean: 4.44, SD: 0.66), with good haptics (mean: 4.10, SD: 0.97)
      and didactic value (mean 4.10, SD: 0.65). CONCLUSIONS: This study established the
      face validity of the ProMIS augmented reality simulator for "basic skills" and
      "suturing and knot-tying" tasks. ProMIS was considered a good tool for training
      in laparoscopic skills for surgical residents and surgeons.

PMID- 19088649
TI  - Generating classes of 3D virtual mandibles for AR-based medical simulation.
AB  - INTRODUCTION: Simulation and modeling represent promising tools for several
      application domains from engineering to forensic science and medicine. Advances
      in 3D imaging technology convey paradigms such as augmented reality (AR) and
      mixed reality inside promising simulation tools for the training industry.
      METHODS: Motivated by the requirement for superimposing anatomically correct 3D
      models on a human patient simulator (HPS) and visualizing them in an AR
      environment, the purpose of this research effort was to develop and validate a
      method for scaling a source human mandible to a target human mandible within a 2
      mm root mean square (RMS) error. RESULTS: Results show that, given a distance
      between 2 same landmarks on 2 different mandibles, a relative scaling factor may
      be computed. Using this scaling factor, results show that a 3D virtual mandible
      model can be made morphometrically equivalent to a real target-specific mandible
      within a 1.30 mm RMS error. CONCLUSION: The virtual mandible may be further used
      as a reference target for registering other anatomic models, such as the lungs,
      on the HPS. Such registration will be made possible by physical constraints among
      the mandible and the spinal column in the horizontal normal rest position.

PMID- 19088650
TI  - Evaluation of a documentation system for airway management training.
AB  - INTRODUCTION: Resuscitation science is a dynamic part of healthcare training,
      with an expanding role for simulation. Historically, performance measurement and
      documentation relied upon the presence of an instructor, an expensive and
      potentially inaccurate assessment tradition that tied performance testing to a
      fixed facility. We hypothesize that an automated system might be developed and
      validated to document performance in airway management for self assessment in the
      absence of a human trainer. The system would also store and transmit data to a
      central registry to document skill acquisition and maintenance. METHODS: Multiple
      video and pressure inputs captured and documented resuscitation task performance
      on a readily available standard practice manikin. Bag-valve-mask ventilation
      (BVM), endotracheal intubation, and ventilation via endotracheal tube (ETT) were
      studied for accuracy, adequacy, and time. The 12 participants performed each task
      for 5 repetitions, resulting in 60 total attempts for each skill. RESULTS: Twelve
      untrained participants performed 3 critical tasks in airway management. Review
      with the system informed the participant of his/her performance and desired
      outcome. The system also documented skill performance objectively relative to a
      standard, recording both successes and failures. Compressed and abstracted
      performance records populated an average 14-megabyte file size (excluding full
      motion video). DISCUSSION: This system was successfully used to document student
      performance of BVM, orotracheal intubation, and ventilation via ETT. The system
      easily integrates documentation, including text reports, airway pressure
      readings, still images and videos of task performance. Such digital documentation
      could guide skill acquisition and quantitatively certify performance with minimal
      reliance upon an instructor and evaluator.

PMID- 19088651
TI  - Effective management of sarin exposure: simulation case scenario.
AB  - Biological and chemical warfare training is often overlooked in residency
      programs, but is nonetheless an extremely important part of the curriculum and
      should be implemented before allowing residents to graduate. The purpose of this
      case is twofold: (1) explore the diagnosis and treatment of Sarin exposure, (2)
      discuss the methods of protecting against contamination with toxic agents.

PMID- 19088652
TI  - Obstetric simulation as a risk control strategy: course design and evaluation.
AB  - INTRODUCTION: Patient safety initiatives aimed at reducing medical errors and
      adverse events are being implemented in Obstetrics. The Controlled Risk Insurance
      Company (CRICO), Risk Management Foundation (RMF) of the Harvard Medical
      Institutions pursued simulation as an anesthesia risk control strategy.
      Encouraged by their success, CRICO/RMF promoted simulation-based team training as
      a risk control strategy for obstetrical providers. We describe the development,
      implementation, and evaluation of an obstetric simulation-based team training
      course grounded in crisis resource management (CRM) principles. METHODS: We
      pursued systematic design of course development, implementation, and evaluation
      in 3 phases, including a 1-year or more posttraining follow-up with self
      assessment questionnaires. RESULTS: The course was highly rated overall by
      participants immediately after the course and 1-year or more after the course.
      Most survey responders reported having experienced a critical clinical event
      since the course and that various aspects of their teamwork had significantly or
      somewhat improved as a result of the course. Most (86%) reported CRM principles
      as useful for obstetric faculty and most (59%) recommended repeating the
      simulation course every 2 years. CONCLUSIONS: A simulation-based team-training
      course for obstetric clinicians was developed and is a central component of
      CRICO/RMF's obstetric risk management incentive program that provides a 10%
      reduction in annual obstetrical malpractice premiums. The course was highly
      regarded immediately and 1 year or more after completing the course. Most survey
      responders reported improved teamwork and communication in managing a critical
      obstetric event in the interval since taking the course. Simulation-based CRM
      training can serve as a strategy for mitigating adverse perinatal events.

PMID- 19088653
TI  - How to create a clinical data station for use in a high fidelity medical
      simulation lab.
AB  - INTRODUCTION: Many advances have been made in the capabilities of high-fidelity
      medical simulators such that they have become increasingly more life-like. To
      create a more life-like experience, it is important to incorporate into the
      simulation environment as many features found in the real life setting as
      possible. One of these features is the delivery of diagnostic information.
      METHODS: We have assembled a very cost-effective data station that allows for the
      real-time delivery of laboratory values, electrocardiograms, and radiologic
      studies in a manner which is most similar to that which exists in real Emergency
      Departments. RESULTS: This data station allows for a more realistic simulated
      patient encounter. It helps participants hone skills involved in radiographic
      interpretation using an interface found in the hospital. It also facilitates
      smooth flow of events by streamlining the delivery of laboratory and
      electrocardiographic data. CONCLUSIONS: Utilizing this data station has allowed
      us to increase the efficiency of our scenarios, improve participant satisfaction,
      and offer some additional practice at interpreting data as it would be viewed in
      the hospital.

PMID- 19088654
TI  - Moulage in high-fidelity simulation-a chest wall burn escharotomy model for
      visual realism and as an educational tool.
AB  - INTRODUCTION: There is a paucity of literature pertaining to the role and
      techniques of moulage for creating high-fidelity medical simulations. As part of
      an Intensive Care Crisis Event Management Course, simulation of an extensive
      torso burn was desired. The aim of the moulage was to enhance the realism of the
      scenario but additionally to enable a chest wall escharotomy to be performed.
      METHODS: A simple step-wise technique for preparing a chest wall burn moulage
      that may be fitted to mannequins of all sizes and shapes is described. RESULTS:
      Utilization of the chest wall moulage as part of an overall strategy to prepare
      mannequins' for a severe burns scenario is detailed. CONCLUSIONS: In the case of
      the chest wall burn model, moulage was used as more than a visual realism
      enhancing strategy-it served as an educational tool in its own right, permitting
      demonstration of a procedure performed infrequently outside the walls of major
      burns centers.

PMID- 19088655
TI  - Being smarter about SMARTER: A commentary on "a measurement tool for simulation
      based training in emergency medicine: the simulation module for assessment of
      resident targeted event responses approach".

PMID- 19088656
TI  - Absolute and relative value of patient simulator features as perceived by medical
      undergraduates.
AB  - BACKGROUND: Patient simulators incorporate a range of technical features. An
      understanding of which features are most valuable and which may be less so is
      important for simulator design and utilization. In this study, we attempted to
      answer the question of whether or not certain simulator features are perceived by
      learners as more useful than others in achieving specified educational
      objectives. METHODS: The subjects were third and fourth year medical students
      participating in an Emergency Medicine Simulation Workshop (n = 97). Following
      the Workshop, subjects rated each of 13 simulator features on a 5-point scale
      from distracting to extremely useful in achieving specified educational
      objectives; and then identified the most and least useful features. RESULTS:
      There were significant differences between the scores of the most highly rated
      features (vital sign display, interactive voice, chest rise, and palpable pulse),
      and those of the features with the lowest ratings (abnormal breath sounds,
      prerecorded voice, IV arm, and heart tones) (4.75 vs. 3.93, P < 0.0001). Three
      features (heart tones, abnormal breath sounds, and prerecorded voice) were rated
      by more than one third of the students as distracting, not useful, or uncertain
      if useful. On the ranking scale, highly rated features tended to be identified as
      most useful, and those with the lowest ratings were more often ranked as least
      useful. There was a statistically significant (P < 0.0001) correlation between
      rating and rankings. CONCLUSIONS: There are significant differences in the
      perceived usefulness of patient simulator features. This has implications both
      for simulator design and for simulator-based education.

PMID- 19088657
TI  - The use of cognitive AIDS during simulated pediatric cardiopulmonary arrests.
AB  - BACKGROUND: Management of pediatric cardiopulmonary arrest (CPA) is challenging
      because of the low volume of experience of most pediatric health care providers.
      Use of cognitive aids may assist in making rapid decisions in these crises;
      however, there are no known published reports on whether these aids are actually
      used during arrest management and whether they impact quality of care. METHODS:
      Sixty pediatric residents participated in individual simulated CPA scenarios,
      which involved pulseless ventricular tachycardia and pulseless electrical
      activity. Our primary outcome measure was the proportion of pediatric residents
      who used cognitive aids during simulated CPAs. Secondary outcome measures were to
      quantify 1) type of aids used, 2) category of use, and 3) human errors made
      during resuscitation efforts. RESULTS: Eighty-five percent of residents
      voluntarily used a cognitive aid to assist in managing simulated pediatric CPAs.
      The most commonly used aids were an American Heart Association Pediatric Advanced
      Life Support aid and an institutionally created aid. Forty-three of 51 (84.3%)
      and 23 of 46 (60.5%) residents used these aids for assistance with the pulseless
      ventricular tachycardia and pulseless electrical activity algorithm,
      respectively. Unfortunately, 13 of 51 (25.5%) residents chose the incorrect
      treatment algorithm, resulting in inappropriate management. CONCLUSION AND
      APPLICATION: Although the majority of residents chose to use cognitive aids for
      assistance, errors in management were common. Further study is required to
      determine whether these errors are associated with cognitive aid design flaws and
      whether improving their design through human factors research can help minimize
      errors in Basic and Advanced Life Support, ultimately improving patient outcomes.

PMID- 19088658
TI  - Design, development, and evaluation of an online virtual emergency department for
      training trauma teams.
AB  - BACKGROUND: Training interdisciplinary trauma teams to work effectively together
      using simulation technology has led to a reduction in medical errors in emergency
      department, operating room, and delivery room contexts. High-fidelity patient
      simulators (PSs)-the predominant method for training healthcare teams-are
      expensive to develop and implement and require that trainees be present in the
      same place at the same time. In contrast, online computer-based simulators are
      more cost effective and allow simultaneous participation by students in different
      locations and time zones. In this pilot study, the researchers created an online
      virtual emergency department (Virtual ED) for team training in crisis management,
      and compared the effectiveness of the Virtual ED with the PS. We hypothesized
      that there would be no difference in learning outcomes for graduating medical
      students trained with each method. METHODS: In this pilot study, we used a
      pretest-posttest control group, experimental design in which 30 subjects were
      randomly assigned to either the Virtual ED or the PS system. In the Virtual ED
      each subject logged into the online environment and took the role of a team
      member. Four-person teams worked together in the Virtual ED, communicating in
      real time with live voice over Internet protocol, to manage computer-controlled
      patients who exhibited signs and symptoms of physical trauma. Each subject had
      the opportunity to be the team leader. The subjects' leadership behavior as
      demonstrated in both a pretest case and a posttest case was assessed by 3 raters,
      using a behaviorally anchored scale. In the PS environment, 4-person teams
      followed the same research protocol, using the same clinical scenarios in a
      Simulation Center. Guided by the Emergency Medicine Crisis Resource Management
      curriculum, both the Virtual ED and the PS groups applied the basic principles of
      team leadership and trauma management (Advanced Trauma Life Support) to manage 6
      trauma cases-a pretest case, 4 training cases, and a posttest case. The subjects
      in each group were assessed individually with the same simulation method that
      they used for the training cases. RESULTS: Subjects who used either the Virtual
      ED or the PS showed significant improvement in performance between pretest and
      posttest cases (P < 0.05). In addition, there was no significant difference in
      subjects' performance between the 2 types of simulation, suggesting that the
      online Virtual ED may be as effective for learning team skills as the PS, the
      method widely used in Simulation Centers. Data on usability and attitudes toward
      both simulation methods as learning tools were equally positive. DISCUSSION: This
      study shows the potential value of using virtual learning environments for
      developing medical students' and resident physicians' team leadership and crisis
      management skills.

PMID- 19088659
TI  - Use of simulation based team training for obstetric crises in resident education.
AB  - BACKGROUND: Obstetric crises are unexpected and random. Traditionally, medical
      training for these acute events has included lectures combined with arbitrary
      clinical experiences. This educational paradigm has inherent limitations. During
      actual crises insufficient time exists for discussion and analysis of patient
      care. Our objective was to create a simulation program to fill this experiential
      gap. METHODS: Ten L&D teams participated in high fidelity simulation training. A
      team consisted of two or three nurses, one anesthesia resident and one or two
      obstetric residents. Each team participated in two scenarios; epidural-induced
      hypotension followed by an amniotic fluid embolism. Each simulation was followed
      by a facilitated debriefing. All simulations were videotaped. Clinical
      performances of the obstetric residents were graded by two reviewers using the
      videotapes and a faculty-developed checklist. Recurrent errors were analyzed and
      graded using Health Failure Modes Effects Analysis. All team members completed a
      course evaluation. RESULTS: Performance deficiencies of the obstetric residents
      were identified by an expert team of reviewers. From this list of errors, the
      "most valuable lessons" requiring further focused teaching were identified and
      included 1) Poor communication with the pediatric team, 2) Not assuming a
      leadership role during the code, 3) Poor distribution of workload, and 4) Lack of
      proper use of low/outlet forceps. Participants reported the simulation course
      allowed them to learn new skills needed by teams during a crisis. CONCLUSION:
      Simulated obstetric crises training offers the opportunity for educators to
      identify specific performance deficits of their residents and the subsequent
      development of teaching modules to address these weaknesses.

PMID- 19088660
TI  - Strengths and weaknesses of simulated and real patients in the teaching of skills
      to medical students: a review.
AB  - The aim of this review was to identify the strengths and weaknesses of the roles
      of real and simulated patients in undergraduate medical education. The literature
      was reviewed in relation to four patient roles: real patients as educational
      "resource" (passive role), real patients as teachers (active role), and simulated
      patients as educational resource and teachers. Each of the four patient roles was
      found to have specific advantages and disadvantages from the perspectives of
      teachers, students, and patients. For example, advantages of real patients as
      educational resource were patient-centered learning and high patient
      satisfaction. Disadvantages were their limited availability and the variability
      in learning experiences among students. Despite the considerable amount of
      literature we found, many gaps in knowledge about patient roles in medical
      education remain and should be addressed by future studies.

PMID- 19088661
TI  - A measurement tool for simulation-based training in emergency medicine: the
      simulation module for assessment of resident targeted event responses (SMARTER)
      approach.
AB  - The use of simulation in graduate medical education affords unique opportunities
      for increasing the quality of a resident's educational experiences. Additionally,
      simulation poses a set of challenges that must be met to realize the full
      potential on learning and assessment practices. This article presents a
      methodology for creating simulation scenarios and accompanying measurement tools
      that are systematically linked in a direct and explicit manner to the
      Accreditation Council for Graduate Medical Education (ACGME) core competencies.
      This method, the Simulation Module for Assessment of Resident's Targeted Event
      Responses (SMARTER), is an 8 step process that addresses the critical challenges
      of performance measurement in simulations and the need to document Accreditation
      Council for Graduate Medical Education core competency based learning outcomes.
      The SMARTER methodology is discussed in detail and 3 examples of scenario content
      and measurement tools generated with the SMARTER approach are provided.
      Additionally, results from an initial evaluation of the practicability and
      utility of the SMARTER measurement tools are discussed.

PMID- 19088662
TI  - Inconspicuous portable audio/visual recording: transforming an IV pole into a
      mobile video capture stand.
AB  - INTRODUCTION: Although a traditional simulation laboratory may have excellent
      installed audio/visual capabilities, often large classes overwhelm the limited
      space in the laboratory. With minimal monetary investment, it is possible to
      create a portable audio/visual stand from an old IV pole. METHODS: An IV pole was
      transformed into an audio/visual stand to overcome the burden of transporting
      individual electronic components during a patient safety research project
      conducted in an empty patient room with a standardized patient. The materials and
      methods for making the modified IV pole are outlined in this article. RESULTS:
      The limiting factor of production is access to an old IV pole; otherwise a few
      purchases from an electronics store complete the audio/visual IV pole.
      CONCLUSIONS: The modified IV pole is a cost-effective and portable solution to
      limited space or the need for audio/visual capabilities outside of a simulation
      laboratory. The familiarity of an IV pole in a clinical setting reduces the
      visual disturbance of relocated audio/visual equipment in a room previously void
      of such instrumentation.

PMID- 19088663
TI  - 2007 simulation education summit.
AB  - The Society for Simulation in Healthcare convened the second Simulation Education
      Summit meeting in October 2007 in Chicago, Illinois. The purpose of the Summit
      was to bring together leaders of public, private, and government organizations,
      associations, and agencies involved in healthcare education for a focused
      discussion of standards for simulation-based applications. Sixty-eight
      participants representing 36 organizations discussed in structured small and
      large groups the criteria needed for various training and assessment applications
      using simulation. Although consensus was reached for many topics, there were also
      areas that required further thought and dialogue. This article is a summary of
      the results of these discussions along with a preliminary draft of a guideline
      for simulation-based education.

PMID- 19088664
TI  - Effective management of sarin exposure: simulation case scenario.

PMID- 19088665
TI  - Using simulation to orient code blue teams to a new hospital facility.
AB  - OBJECTIVES: Prompt and successful cardiopulmonary resuscitation during a sudden
      cardiac arrest can be hindered by multiple variables, ie, ineffective
      communication, stress, lack of training, and an unfamiliar environment, such as a
      new hospital facility. The main objective of the study was to use high-fidelity
      simulations to orient Code Blue Teams (CBTs) to critical events in a new hospital
      facility. A secondary objective was to elucidate factors that may have
      contributed to responses by debriefing teams. METHODS: Mock Code Blue exercises
      using high-fidelity simulation were implemented in real workplace settings to
      orient CBTs to critical events. We measured arrival time of first responder,
      crash cart to code site, first six CBT responders, first chest compression, and
      first electrical shock. After each mock code, participants were debriefed to
      assess any barriers to effective response and decision making. RESULTS: Twelve
      mock codes were conducted at different locations of the new facility. Sixty-nine
      percent of the participants reported that the training was beneficial. The median
      time of arrival of the first responders was 42 seconds and the first CBT member
      was 66 seconds. The median time to initiation of chest compressions was 80
      seconds, crash cart arrival was 68 seconds, and first electrical shock was 341
      seconds. An additional outcome of the study was the identification of facility
      and systems issues that had the potential to impact patient safety. CONCLUSIONS:
      Clinical simulation can be effectively used to orient CBTs and identify critical
      safety issues in a newly constructed healthcare facility.

PMID- 19088666
TI  - Validation of a tool to measure and promote clinical teamwork.
AB  - OBJECTIVE: Human factors and teamwork are major contributors to sentinel events.
      A major limitation to improving human factors and teamwork is the paucity of
      objective validated measurement tools. Our goal was to develop a brief tool that
      could be used to objectively evaluate teamwork in the field during short clinical
      team simulations and in everyday clinical care. STUDY DESIGN: A pilot validation
      study. Standardized videos were created demonstrating poor, average, and
      excellent teamwork among an obstetric team in a common clinical scenario
      (shoulder dystocia). Three evaluators all trained in Crew Resource Management,
      and unaware of assigned teamwork level, independently reviewed videos and
      evaluated teamwork using the Clinical Teamwork Scale (CTS). Statistical analysis
      included calculation of the Kappa statistic and Kendall coefficient to evaluate
      agreement and score concordance among raters, and Interclass Correlation
      Coefficient (ICC) to evaluate interrater reliability. The reliability of the tool
      was further evaluated by estimating the variance of each component of the tool
      based on generalizability theory. RESULTS: There was substantial agreement (Kappa
      0.78) and score concordance (Kendall coefficient 0.95) among raters, and
      excellent interrater reliability (interclass correlation coefficient 0.98). The
      highest percentage of variance in scores among raters was because of rater/item
      interaction. CONCLUSION: The CTS was developed to efficiently measure key
      clinical teamwork skills during simulation exercises and in everyday clinical
      care. It contains 15 questions in 5 clinical teamwork domains (communication,
      situational awareness, decision-making, role responsibility, and patient
      friendliness). It is easy to use and has construct validity with median ratings
      consistently corresponding with the intended teamwork level. The CTS is a brief,
      straightforward, valid, reliable, and easy-to-use tool to measure key factors in
      teamwork in simulated and clinical settings.

PMID- 19088667
TI  - Professionalism and communication in the intensive care unit: reliability and
      validity of a simulated family conference.
AB  - OBJECTIVE: An Objective Structured Clinical Exam was designed to assess
      physician's ability to discuss end-of-life (EOL) and disclose iatrogenic
      complications (DOC) with family members of intensive care unit patients. The
      study explores reliability and validity based on scores from contrasting rater
      groups (clinicians, SPs, and examinees). METHODS: Two 20-minute stations were
      administered to 17 surgical residents and 2 critical fellows at a university
      based training program. The exam was conducted, videotaped, and scored in a
      standardized setting by 8 clinical raters (MD and RN) and 8 standardized families
      using separate rating tools (EOL and DOC). Examinees assessed themselves using
      the same tools. We analyzed the internal consistency, inter-rater agreement, and
      discriminant validity of both cases using data from each rater group. Cross-rater
      group comparisons were also made. RESULTS: The internal consistency reliability
      correlations were above 0.90 regardless of case or rater group. Within rater
      groups, raters were within 1 point of agreement (5-pt and 6-pt scales) on 81% of
      the DOC and between 74% and 79% of the EOL items. Family raters were more
      favorable than clinical raters in scoring DOC, but not EOL cases. Large raw
      differences in performance by training level favored more experienced trainees
      (3rd year residents and fellows). These differences were statistically
      significant when based on residents own self-ratings, but not when they were
      based on clinical or family ratings. DISCUSSION: The Family Conference Objective
      Structured Clinical Exam is a reliable exam with high content validity. It seems
      unique in the literature for assessing surgical trainees' ability to discuss "bad
      news" with family members in intensive care.

PMID- 19088668
TI  - Epistaxis simulator: an innovative design.
AB  - INTRODUCTION: This article provides directions for creating a cost-effective
      epistaxis simulator using an existing CPR Trainer and expired medical supplies.
      METHODS: An epistaxis simulator was created and presented to attending Emergency
      Medicine physician-educators at Evanston Northwestern Healthcare as an adjunct
      for procedural training. The materials and methods for making the nosebleed
      simulator are outlined in this article. RESULTS: We created an epistaxis model
      utilizing an older CPR Trainer, i.v. tubing, and a bag of normal saline. The
      model provided realistic epistaxis. This simulator is able to simulate a
      nosebleed's response to proper positioning of nasal packing by creating
      hemostasis. CONCLUSIONS: Existing task trainers can be modified to provide
      learners with novel features that can expand the number of simulated clinical
      conditions.

PMID- 19088669
TI  - High degree of realism in teaching percutaneous coronary interventions by
      combining a virtual reality trainer with a full scale patient simulator.
AB  - The virtual reality coronary angiography simulator "CATHI" (Catheter Instruction
      System, Mannheim, Germany) simulates coronary arteries with implemented vessel
      lesions in virtual patients. Like similar systems the software model runs on
      common PC systems, which are linked to the mechanical device for manual training.
      We combined the advantages of this skill trainer with the near to reality
      assembly of a cardiac catheterization laboratory (Cath-lab) by connecting it to a
      full scale simulator (HPS, METI, Sarasota, FL). We present two methods of
      synchronizing the heartbeat between both simulation devices. Method A-the
      hardware solution-uses the electrocardiogram-synchronization signal of the HPS as
      a pacemaker for CATHI's heartbeat. Method B, a more sophisticated software
      solution, uses a communication protocol between the HPS software and the CATHI
      system to realize bi-directional data exchange. In 14 identical courses we
      performed four different scenarios using the above described setup, all of which
      had to be undergone by the 143 participants (including nursing staff, experienced
      and inexperienced cardiologists). The synchronization of the two systems
      contributed to a close to reality situation. Scenario control was accomplished
      via commercially available HPS-software. Tachycardic and bradycardic arrhythmias
      were predetermined by predefined scenarios of the HPS-software, the trainee's
      intervention resulting in realistic treatment outcomes. Using either method, the
      transmitted signals resulted in the same heartbeat in the CATHI-system, making
      the cardiologic interventions more difficult but more realistic.

PMID- 19088673
TI  - Abstracts of the 8th International Meeting on Simulation in Healthcare. January
      13-16, 2008. San Diego, California, USA.

PMID- 19088689
TI  - The evolution in the use of MIBG in more than 25 years of experimental and
      clinical applications.
AB  - Radioiodinated metaiodobenzylguanidine (MIBG), or Iobenguane, was developed in
      the late 1970s at the Michigan University Medical Center for imaging the adrenal
      medulla and its diseases, and was rapidly extended to depict a wide range of
      tumors of neural crest origin. Because of its high and selective uptake and
      retention by these tumors, careful consideration was also given to the
      therapeutic potential of [(131)I]MIBG. Beside imaging and therapy of
      neuroendocrine tumors, the possibility of in vivo assessment of cardiac
      sympathetic neuronal activity led recently to a renewed interest for MIBG
      scintigraphy and this application is still expanding. In this paper, we review
      the evolution in the use of MIBG in more than 25 years of experimental and
      clinical applications, with attention also to the developments in radiochemistry
      and instrumentation. A literature search in PubMed based on
      ''metaiodobenzylguanidine or MIBG'' was conducted; from this analysis, it appears
      that the use of MIBG evolved from nearly exclusively oncology (both for diagnosis
      and therapy) to new applications mainly aimed to study the sympathetic neuronal
      integrity of the heart. Those currently exceed those about imaging of tumor
      diseases. We also report the geographic distribution of published papers.

PMID- 19088690
TI  - Meta-iodobenzylguanidine and analogues: chemistry and biology.
AB  - Meta-iodobenzylguanidine (MIBG) is a structural analogue of the neurotransmitter
      norepinephrine (NE) and is taken up by cells rich in sympathetic neurons by an
      active uptake process mediated by the NE transporter, which is referred to as
      uptake-1. It is a valuable agent in the diagnosis of myocardial abnormalities as
      well as that of several neuroendocrine tumors such as neuroblastoma,
      pheochromocytoma and carcinoid tumors. MIBG labeled with (131)I also is used
      extensively in the therapy of several neuroendocrine tumors. Over the years, a
      substantial amount of work has been undertaken to improve its clinical utility.
      Currently, radio-iodinated MIBG used in the clinic is prepared by an exchange
      radio-iodination method and, thus, is of low specific activity. For possible
      better targeting and to ward off pharmacological effects, its preparation at a no
      carrier-added level both by solution-phase and solid-phase synthesis has been
      developed. For potential use in the treatment of micrometastatic diseases,
      synthesis of an analogue labeled with the a emitter (211)At was devised.
      Development of analogues labeled with positron emitting radionuclides such as
      (124)I, (18)F, and (76)Br has been reported. Further, efforts have been put in to
      improve its pharmacokinetic properties by structural modifications. Various
      aspects of these developments are reviewed herein.

PMID- 19088691
TI  - Cardiac 123I-MIBG scintigraphy in heart failure.
AB  - This review focuses on myocardial [(123)I]mIBG imaging in patients with
      cardiomyopathy and heart failure (HF). In particular, the potential role of
      myocardial (123)I-mIBG scintigraphy in the prediction of potentially fatal
      arrhythmic events is described. A growing body of evidence supports the use of
      cardiac sympathetic innervation imaging, specifically using (123)I-mIBG, to risk
      stratify patients with HF. Cardiac sympathetic imaging can help to improve
      understanding of the mechanisms responsible for increased sympathetic activity in
      HF, and how sympathetic over-activity exerts its deleterious actions. Eventually,
      this may result in more effective therapies and, thereby, better outcome for
      these patients. Assessment of cardiac sympathetic activity could also contribute
      to a more appropriate selection of individual patients for implantable
      cardioverter-defibrillators (ICD).

PMID- 19088692
TI  - Iodine-123-MIBG sympathetic imaging in Lewy-body diseases and related movement
      disorders.
AB  - Iodine-123-labeled metaiodobenzylguanidine (MIBG) has a history of over 20 years
      as a marker of myocardial sympathetic activity in Japan and has been used for
      various cardiac diseases. Aside from conventional utilities in patients with
      cardiac diseases, including ischemic heart diseases, cardiomyopathy, heart
      failure and diabetes, neurological disorders have recently been drawing special
      attention. The [(123)I]MIBG study showed markedly decreased myocardial uptake in
      Parkinson's disease, dementia with Lewy bodies and pure autonomic failure, which
      is a common feature of Lewy-body diseases. The MIBG study can be used for
      differentiating patients with extrapyramidal signs and dementia. The unique
      application of MIBG in movement disorders and related neurological diseases is
      one of its most common uses in Japan, and further studies are expected worldwide.

PMID- 19088693
TI  - MIBG scintigraphy for the diagnosis and follow-up of children with neuroblastoma.
AB  - Neuroblastoma (NBL) is the commonest extra-cranial solid tumor in children and
      the leading cause of cancer related deaths in childhood between the age of 1 to 4
      years. NBL may behave in very different ways, from the less aggressive stage 4S
      NBL or congenital forms that may resolve without treatment in up to 90% of the
      children, to the high-risk disseminated stage 4 disease in older children with a
      cure rate of 35 to 40%. Initial staging is crucial for effective management and
      radiolabeled metaiodobenzylguanidine (MIBG) with iodine-123 is a powerful tool
      with a sensitivity around 90% and a specificity close to 100% for the diagnosis
      of NBL. MIBG scintigraphy is used routinely and is mandatory in most
      investigational clinical trials both for the initial staging of the disease, the
      evaluation of the response to treatment, as well as for the detection of
      recurrence during follow-up. With respect to outcome of children presenting
      disseminated stage 4 NBL, the role of post-therapeutic [(123)I]MIBG scan has been
      investigated by several groups but so far there is no consensus whereas a
      complete or very good partial response as assessed by MIBG may be of prognostic
      value. NBL needs a multimodality approach at diagnosis and during follow-up and
      MIBG scintigraphy keeps its pivotal role, in particular with respect to bone
      marrow involvement and/or cortical bone metastases.

PMID- 19088695
TI  - Detection and treatment of pheochromocytomas and paragangliomas: current standing
      of MIBG scintigraphy and future role of PET imaging.
AB  - Pheochromocytomas are rare tumors arising from chromaffin cells of adrenal
      medullary or extra-adrenal paraganglionic tissue. These tumors are characterized
      by synthesis, storage, metabolism and secretion of catecholamines. Similar to the
      sympathetic nervous system, pheochromocytomas express cellular norepinephrine
      transporters (NET) through which catecholamines can enter pheochromocytoma cells
      to be stored in vesicles. Metaiodobenzylguanidine (MIBG) resemblance to
      norepinephrine and its good affinity and uptake by NET resulted in its use in
      pheochromocytoma diagnosis from 1981. Both [(123)I]MIBG and [(131)I]MIBG (lower
      sensitivity) scintigraphy are used for localization of these tumors. Recent
      discoveries of different hereditary syndromes associated with pheochromocytomas
      led to the identification of several and new distinct genotype-phenotype
      associations. Importantly, with this distinction of clinical phenotypes, MIBG was
      found to have a different performance in subsets of pheochromocytoma patients.
      Reduced sensitivity of MIBG scintigraphy in some familial paraganglioma
      syndromes, malignant disease and extra-adrenal paragangliomas has been found.
      Therefore, newer compounds, especially for positron emission tomography (PET),
      such as [(11)C]hydroxyephedrine ([(11)C]HED), [(18)F]fluoro-2-deoxy-D-glucose
      ([(18)F]FDG), [(18)F]fluoro-dihydroxyphenylalanine ([(18)F] FDOPA) and
      [(18)F]fluorodopamine ([(18)F]FDA) have emerged and were found to be superior to
      MIBG in the localization of certain types of pheochromocytoma and paragangliomas.
      Finally, using [(131)I]MIBG represents an important treatment option in patients
      with malignant pheochromocytoma, but the development of newer treatment
      modalities is expected. In this review, we provide the reader with an overview of
      the current standing of [(123)I]- and [(131)I]MIBG in diagnosis and treatment of
      pheochromocytoma amongst the newer PET imaging agents.

PMID- 19088694
TI  - Radiolabeled metaiodobenzylguanidine for imaging and therapy of neuroblastoma.
AB  - Neuroblastoma is an embryonic tumor of the peripheral sympathetic nervous system,
      and is able to take up, store and secrete catecholamine metabolites. Neuro
      blastoma is metastatic or otherwise high risk for relapse in nearly 50% of cases,
      with a long-term survival of <40%, necessitating new approaches to therapy. The
      tumor cells express the norepinephrine transporter, which makes
      metaiodobenzylguanidine (MIBG), an analogue of norepinephrine, an ideal tumor
      specific agent for imaging and therapy, when labeled with (123)I or (131)I. This
      article will briefly review the use of [(123)I]MIBG imaging for monitoring
      therapy in neuroblastoma, and concentrate on the past, current and planned
      clinical trials using [(131)I]MIBG as targeted radiotherapy. The administration
      guidelines, toxicity, response and survival are discussed. Various therapeutic
      approaches include MIBG monotherapy, sequential infusion, and combination
      therapy. Treatment with MIBG has been tested as induction therapy, part of
      consolidation, and as treatment for relapse. The high response rates of 30-40%
      using MIBG monotherapy in relapsed neuroblastoma, and the low non-hematologic
      toxicity make this an ideal agent for incorporation into standard therapy of high
      risk neuroblastoma.

PMID- 19088696
TI  - MIBG for diagnosis and therapy of medullary thyroid carcinoma: is there still a
      role?
AB  - Medullary thyroid carcinoma (MTC) is a relatively rare neuroendocrine tumour
      originating from the parafollicular C cells and releases calcitonin (hCt),
      carcinoembryonic antigen (CEA) and occasionally other substances. In 20-30% of
      cases MTC presents a germline mutation of the RET proto-oncogene and occurs in 3
      different hereditary forms: familial MTC, multiple endocrine neoplasia (MEN) 2A
      and MEN 2B syndrome. Prognosis of MTC is largely related to tumour extension at
      disease onset. Surgery remains the most effective therapy for potential cure.
      Overall survival is strictly linked to the occurrence of relapse. After surgery,
      serum hCt remains the most sensitive test for occult disease. Diagnostic imaging
      work-up includes ultrasound, computed tomography (CT), magnetic resonance imaging
      (MRI), bone scintigraphy, as the more frequent sites of recurrence or metastases
      are cervical and mediastinal lymph nodes, lungs, liver and bone. Nuclear medicine
      procedures include (111)In-labelled somatostatin analogs, radioiodinated
      metaiodobenzylguanidine (MIBG), and several PET radiopharmaceuticals. Experience
      with radionuclide therapy in MTC is restricted to few patients treated with
      (131)I-MIBG or (90)Y-DOTATOC. Since 1987, 1 027 diagnostic MIBG scans were
      performed in the Department Department of Diagnostic Imaging and Therapy of the
      Istituto Nazionale Tumori IRCCS Foundation (Milan, Italy), 85 of which for MTC,
      with a sensitivity of 38.7% in patients with evidence of disease and 30.7 % if
      all patients were considered. Since 1994, 13 MTC patients were treated with MIBG
      with 4 partial responses and 4 stable diseases. Patients with liver or bone
      involvement responded to therapy and showed long-term partial remission of
      disease, others showed stability of disease, which was apparently unrelated to
      therapy. Improvement of efficacy can be achieved through dosimetric calculation
      of administered activity.

PMID- 19088697
TI  - Radioiodinated metaiodobenzylguanidine in the diagnosis and therapy of carcinoid
      tumors.
AB  - Carcinoid tumors account for less than 1% of all malignancies and the majority
      arises in the gastrointestinal system. These tumors are slow-growing compared
      with adenocarcinomas and they differ from the other neuroendocrine malignancies
      by their protean clinical presentation. Carcinoid tumors were previously
      considered indolent, but they can manifest malignant characteristics with
      metastatic spread which often results in a poor prognosis. Although there have
      been advances in diagnostic and treatment modalities, carcinoid tumors are still
      frequently diagnosed late, often when the tumor has metastasized and patients
      have developed carcinoid syndrome. Diagnosis, prognosis and treatment options are
      based on biochemical markers and imaging investigations. High concentration of
      urinary 5-HIAA, elevated plasma serotonin and chromogranin A levels help to
      establish the initial diagnosis of carcinoid tumors. In addition to the computed
      tomography and magnetic resonance imaging, molecular imaging modalities such as
      OctreoScan, metaiodobenzylguanidine (MIBG) imaging and more recently PET imaging
      are used in detecting the primary malignancy and metastatic involvement. Surgery
      is the mainstay of treatment of non-metastatic carcinoid tumors. Cytotoxic
      chemotherapy has limited role because of the chemoresistant nature of these
      tumors. Because carcinoid tumors express somatostatin receptors, somatostatin
      analogues, which inhibit release of serotonin and other neuroendocrine peptides,
      are often used, but their use is limited to symptom control. Treatment using high
      doses of radionuclides, such as radiolabeled somatostatin analogues and MIBG, is
      a more recent option, which offers a definite advantage in management. In this
      article, we review the current state of the art in the diagnosis and treatment of
      carcinoid tumors as well as the role of MIBG in their diagnosis and management.

PMID- 19088698
TI  - Bispectral index-guided intraoperative sedation with dexmedetomidine and
      midazolam infusion in outpatient cataract surgery.
AB  - BACKGROUND: This study aimed to evaluate the role of alfa-2 agonist infusion,
      with dexmedetomidine or midazolam, on hemodynamic and respiratory parameters
      while titrating the sedation level with the bispectral index (BIS) during
      cataract surgery. METHODS: Ninety consenting ASA class I-III patients who were
      electively undergoing cataract surgery were enrolled in the double blind study. A
      random infusion of 0.25 microg kg(-1) hr(-1) Dexmedetomidine (Group D), 25 microg
      kg(-1) hr(-1) midazolam (Group M), or saline for controls (Group C) was
      administered after mounting a BIS monitor and routine anesthetic care. The target
      BIS level was >85. An additional bolus dose in 1 mL increments of the study drug
      or cessation of the infusion was adjusted according to the BIS level. Changes in
      respiratory and vital parameters were noted and, in case of mild pain, 25 microg
      fentanyl was administered as a bolus. Pain and sedation were evaluated in the
      early postoperative period using visual analogue and four rating sedation scales.
      RESULTS: In Group D, heart rate decreased in the later periods of surgery (35-50
      min) and in the early postoperative period (5(th) and 15(th) min). Dose
      adjustments were required in six and ten patients in Groups D and M,
      respectively. Pain scores were lower with dexmedetomidine infusion. CONCLUSIONS:
      Dexmedetomidine infusion mildly decreased heart rate in the later periods of
      surgery with better pain scores in the postoperative period. Dexmedetomidine
      should be an alternative for intraoperative sedation in outpatient cataract
      surgery.

PMID- 19088699
TI  - Therapeutic hypothermia in Italian intensive care units: a national survey.
AB  - BACKGROUND: The aim of this study was to investigate the use of therapeutic
      hypothermia (TH) in Italian Intensive Care Units (ICUs). METHODS:  DESIGN AND
      SETTINGS: After being contacted by phone, a structured questionnaire to evaluate
      the use of TH was sent to all Italian ICUs. The questionnaire was aimed at
      determining the extent of TH use (indications, methods employed, target
      temperature, side effects) as well as the reasons why some ICUs did not make use
      of TH for the treatment of cardiac arrest patients. RESULTS: Out of the 448 ICUs
      contacted, 90% (n=404) returned the questionnaire completely filled in. Sixty-six
      responders (16%) made use of TH for post-resuscitation care, and 4% used TH for
      other clinical scenarios (10 ICUs for traumatic brain injury; 5 ICUs for other
      reasons). More than half used TH not only for cardiac arrest subsequent to
      ventricular fibrillation (VF), but also for non-VF cardiac arrest with the
      duration of TH treatment being within the time suggested by advanced cardiac life
      support guidelines. On the other hand, 80% of questionnaire responders did not
      use TH, mainly because they felt they did not have enough data/experience (45%),
      or simply because they had never thought about it (18%). CONCLUSIONS: Despite
      authoritative data supporting its effectiveness and safety, use of TH as part of
      the therapy in a post-resuscitation period in Italian ICUs remains low. The
      reasons for not using it are not completely justified and suggest that an
      educational program is advisable in order to boost the utilization of TH in
      Italy.

PMID- 19088700
TI  - Processing a manuscript submitted to a medical journal.
AB  - Peer review is the process by which manuscripts submitted to medical journals are
      evaluated for scientific soundness and priority, and potentially improved in
      terms of clarity. Constructive interaction between editors, reviewers, and
      authors is critical for the effectiveness of the entire process. Although
      empirical evidence is still limited and is not completely conclusive, it is
      generally accepted that peer review is of the utmost importance for scientific
      progress.

PMID- 19088701
TI  - Stem cells, melanoma and cancer stem cells: the good, the bad and the evil?
AB  - Most cancers contain morphologically heterogeneous populations of cells. While
      this observation may partly be explained by the coexistence of multiple genetic
      sub-clones arising through independent somatic mutations and/or as a result of
      differentiation processes in the tumor microenvironment, it also implies that the
      tumor may be formed from undifferentiated ''stem cell-like'' cells called
      ''cancer stem cells'' or ''cancer-initiating cells''. These cells are thought to
      constitute one or several rare subpopulations in a given tumor and would be
      strongly responsible for initiation of tumor development and growth as well as
      for metastasis and recurrence after cytoreductive therapy. However, while the
      concept of cancer stem cells has been first established for human myeloid
      leukemia in the 1960s, it has only much later been extended to other solid tumors
      such as breast or brain cancers and most recently to melanoma. Thus, it is
      presently unclear which role a sufficiently characterized population of melanoma
      stem cells plays in cancer promotion and progression. Here, we review the
      emerging melanoma stem cell model and discuss the biological and therapeutic
      implications of the model.

PMID- 19088702
TI  - [How the managing role of the coordinator of nuclear medicine changes due to the
      new rules on: "Good preparation of the radiodrugs in nuclear medicine"].

PMID- 19088703
TI  - Efficient intrathymic gene transfer following in situ administration of a rAAV
      serotype 8 vector in mice and nonhuman primates.
AB  - The thymus is the primary site of T-cell development and plays a key role in the
      induction of self-tolerance. We previously showed that the intrathymic (i.t.)
      injection of a transgene-expressing lentiviral vector (LV) in mice can result in
      the correction of a T cell-specific genetic defect. Nevertheless, the efficiency
      of thymocyte transduction did not exceed 0.1-0.3% and we were unable to detect
      any thymus transduction in macaques. As such, we initiated studies to assess the
      capacity of recombinant adeno-associated virus (rAAV) vectors to transduce murine
      and primate thymic cells. In vivo administration of AAV serotype 2-derived single
      stranded AAV (ssAAV) and self-complementary AAV (scAAV) vectors pseudotyped with
      capsid proteins of serotypes 1, 2, 4, 5, and 8 demonstrated that murine thymus
      transduction was significantly enhanced by scAAV2/8. Transgene expression was
      detected in 5% of thymocytes and, notably, transduced cells represented 1% of
      peripheral T lymphocytes. Moreover, i.t. administration of scAAV2/8 particles in
      macaques, by endoscopic-mediated guidance, resulted in significant gene transfer.
      Thus, in healthy animals, where thymic gene transfer does not provide a selective
      advantage, scAAV2/8 is a unique tool promoting the in situ transduction of
      thymocytes with the subsequent export of gene-modified lymphocytes to the
      periphery.

PMID- 19088704
TI  - Rational design leads to more potent RNA interference against hepatitis B virus:
      factors effecting silencing efficiency.
AB  - RNA interference (RNAi) can be an effective antiviral agent; however,
      overexpression of RNAi can be toxic through competition with the endogenous
      microRNA (miRNA) machinery. We used rational design to identify highly potent
      RNAi that is effective at nontoxic doses. A statistical analysis was conducted to
      pinpoint thermodynamic characteristics correlated with activity. Sequences were
      selected that conformed to a consensus internal stability profile (ISP)
      associated with active RNAi, and RNAi triggers were expressed in the context of
      an endogenous miRNA. These approaches yielded highly active hepatitis B virus
      (HBV) RNAi. A statistical analysis found a correlation between activity and
      nucleation by binding within the seed sequence to accessible regions in the
      target RNA. Guide strands were selected for favorable strand biasing, but
      increased strand biasing did not correlate with potency, suggesting a threshold
      effect. Exogenous short hairpin RNAs (shRNAs), but not miRNAs were previously
      reported to compete with miRNAs for the miRNA/RNAi machinery. In contrast, we
      show that exogenous Polymerase III- but not Polymerase II-driven miRNAs compete
      with exogenous miRNAs, at multiple steps in the miRNA pathway. Exogenous miRNAs
      also compete with endogenous miR-21. Thus, competition with endogenous miRNAs
      should be monitored even when using miRNA-based therapeutics. However, potent
      silencing was achieved at doses where competition was not observed.

PMID- 19088707
TI  - New in 2009.

PMID- 19088705
TI  - Mesenchymal stromal cells engineered to express erythropoietin induce anti
      erythropoietin antibodies and anemia in allorecipients.
AB  - Autologous bone marrow mesenchymal stromal cells (MSCs) have been successfully
      used for the delivery of erythropoietin (EPO) in murine models of anemia and
      myocardial infarction. For clinical applications where a transient effect would
      be adequate, such as myocardial infarction, the use of EPO-engineered universal
      donor allogeneic MSCs would be a substantial convenience. We thus investigated
      whether MSCs from C57BL/6 mice would permit robust transient EPO delivery in
      normal BALB/c allorecipients. Implantation of MSCs overexpressing murine EPO led
      to increases in hematocrit in syngeneic and allogeneic mice, but the latter
      eventually developed severe anemia due to acquired neutralizing anti-EPO
      antibodies. As MSCs constitutively produce the CCL2 chemokine which may behave as
      an adjuvant to the anti-EPO immune response, experiments were performed using EPO
      engineered MSCs derived from CCL2(-/-) mice and similar results were obtained. In
      conclusion, MHC-mismatched MSCs can break the tolerance to autoantigens and lead
      to the development of pathogenic autoantibodies.

PMID- 19088708
TI  - Monell chemical senses center.

PMID- 19088709
TI  - The proteasome makes sense of mixed signals.

PMID- 19088710
TI  - Metabolomics cuts to the chase to chase the cuts.

PMID- 19088711
TI  - Engineering fluorination.

PMID- 19088712
TI  - Decoding endocannabinoid signaling.

PMID- 19088713
TI  - A road map of cellular protein homeostasis.

PMID- 19088715
TI  - Amyloid formation by globular proteins under native conditions.
AB  - The conversion of proteins from their soluble states into well-organized
      fibrillar aggregates is associated with a wide range of pathological conditions,
      including neurodegenerative diseases and systemic amyloidoses. In this review, we
      discuss the mechanism of aggregation of globular proteins under conditions in
      which they are initially folded. Although a conformational change of the native
      state is generally necessary to initiate aggregation, we show that a transition
      across the major energy barrier for unfolding is not essential and that
      aggregation may well be initiated from locally unfolded states that become
      accessible, for example, via thermal fluctuations occurring under physiological
      conditions. We review recent evidence on this topic and discuss its significance
      for understanding the onset and potential inhibition of protein aggregation in
      the context of diseases.

PMID- 19088716
TI  - Folate and colorectal cancer prevention.
AB  - Anti-folate chemotherapy agents such as methotrexate and fluorouracil reduce
      proliferation of neoplastic cells by inhibiting DNA synthesis. Paradoxically
      epidemiological data suggests an inverse relationship between dietary folate
      intake and incidence of colorectal cancer (CRC). On the basis of this and other
      putative health benefits around 35% of the North American population take folic
      acid supplements, in addition to natural food folates and fortified flour and
      cereal grains. Recently, randomised controlled trials investigating folic acid as
      a secondary preventative agent in colorectal neoplasia have shed further light on
      the relationship between folate and colorectal carcinogenesis, corroborating data
      from animal models indicating opposing effects dependent on the timing of
      exposure in relation to the development of neoplastic foci. A 'dual-modulator'
      role for folate in colorectal carcinogenesis has been proposed in which moderate
      dietary increases initiated before the establishment of neoplastic foci have a
      protective influence, whereas excessive intake or increased intake once early
      lesions are established increases tumorigenesis. Functional polymorphic variants
      in genes encoding key enzymes in the folate metabolic pathway add a further layer
      of complexity to the relationship between folate and CRC risk. Here, we review
      the evidence concerning the efficacy and safety of folate as a potential CRC
      chemopreventive agent.

PMID- 19088717
TI  - Irinotecan plus carboplatin for patients with carcinoma of unknown primary site.
AB  - Carcinoma of unknown primary site (CUP) is rarely encountered in clinical
      practice and optimal chemotherapy has not yet been established. This phase II
      study was conducted to evaluate the efficacy and toxicity of combined
      irinotecan+carboplatin therapy in chemotherapy-naive patients with CUP.
      Irinotecan was administered at 60 mg m(-2) as a 90-min intravenous infusion on
      days 1, 8 and 15. Carboplatin was administered at an area-under-the curve of 5 mg
      ml(-1) min as a 60-min intravenous infusion on day 1. This cycle was repeated
      every 28 days for up to six cycles. Forty-five patients were enrolled in the
      study. An intent-to-treat analysis revealed an objective response rate to the
      treatment of 41.9% (95% confidence interval, 27.0-57.9%). The median time to
      progression was 4.8 months and the median survival was 12.2 months. The 1- and 2
      year survival rates were 44 and 27%, respectively. The most frequent grade 3 or
      more severe adverse events were leukopaenia (21%), neutropaenia (33%), anaemia
      (25%) and thrombocytopaenia (20%). Thus, the combination of irinotecan plus
      carboplatin was found to be active in patients with CUP. Therefore, the regimen
      may be one of the potentially available chemotherapeutic options for community
      standard of care in patients with a good performance status.

PMID- 19088718
TI  - HER2 gene amplification and EGFR expression in a large cohort of surgically
      staged patients with nonendometrioid (type II) endometrial cancer.
AB  - Type II endometrial cancers (uterine serous papillary and clear cell histologies)
      represent rare but highly aggressive variants of endometrial cancer (EC). HER2
      and EGFR may be differentially expressed in type II EC. Here, we evaluate the
      clinical role of HER2 and EGFR in a large cohort of surgically staged patients
      with type II (nonendometrioid) EC and compare the findings with those seen in a
      representative cohort of type I (endometrioid) EC. In this study HER2 gene
      amplification was studied by fluorescence in situ hybridisation (FISH) and EGFR
      expression by immunohistochemistry. Tissue microarrays were constructed from 279
      patients with EC (145 patients with type I and 134 patients with type II EC). All
      patients were completely surgically staged and long-term clinical follow up was
      available for 258 patients. The rate of HER2 gene amplification was significantly
      higher in type II EC compared with type I EC (17 vs 1%, P<0.001). HER2 gene
      amplification was detected in 17 and 16% of the cases with uterine serous
      papillary and clear cell type histology, respectively. In contrast, EGFR
      expression was significantly lower in type II compared with type I EC (34 vs 46%,
      P=0.041). EGFR expression but not HER2 gene amplification was significantly
      associated with poor overall survival in patients with type II EC, (EGFR, median
      survival 20 vs 33 months, P=0.028; HER2, median survival 18 vs 29 months,
      P=0.113) and EGFR expression retained prognostic independence when adjusting for
      histology, stage, grade, and age (EGFR, P=0.0197; HER2, P=0.7855). We conclude
      that assessment of HER2 gene amplification and/or EGFR expression may help to
      select type II EC patients who could benefit from therapeutic strategies
      targeting both HER2 and EGFR.

PMID- 19088719
TI  - Human xenograft models as useful tools to assess the potential of novel
      therapeutics in prostate cancer.
AB  - With docetaxel as effective chemotherapy for hormone refractory prostate cancer
      (HRPC), the number of new treatment combinations for HRPC is expanding demanding
      a fast-track screening system. This review elaborates on the use of xenograft
      models to select the most promising combination therapies for entering into phase
      II clinical trials.

PMID- 19088720
TI  - A prospective study of peri-diagnostic and surgical wait times for patients with
      presumptive colorectal, lung, or prostate cancer.
AB  - The objective of this study was to prospectively measure peri-diagnostic and
      surgical time intervals for patients with suspected colorectal, lung, or prostate
      cancer. Prospective eligible patients were referred to a regional hospital in
      Ottawa, Canada between February 2004 and February 2005 for diagnostic assessment
      of presumptive colorectal, lung, or prostate cancer. Chart abstractions were used
      to measure nine time intervals; the primary interval was the date of referral for
      diagnostic assessment to the date the patient was informed of the diagnosis.
      Health-related quality-of-life (HRQL) was assessed 5 days following the patient
      being informed of their diagnosis. The median (IQR) time for the primary interval
      was 71 (30-110), 37 (29-49), and 81 (56-100) days for colorectal, lung, and
      prostate patients, respectively (Kruskal-Wallis P=0.0001). This interval was
      significantly less for colorectal patients diagnosed with cancer than for those
      without cancer (median difference=59.0 days; Wilcoxon P=0.003). No differences in
      HRQL existed for patients with cancer and those without. Colorectal and prostate
      patients wait longer between referral for suspected cancer and being informed of
      their diagnosis than current recommendations. The shorter diagnostic intervals
      for colorectal patients with cancer suggest clinicians have an effective process
      for triaging patients referred for diagnostic assessment.

PMID- 19088721
TI  - Incidence and mortality of incidental prostate cancer: a Swedish register-based
      study.
AB  - In a national register-based study of incidence trends and mortality of
      incidental prostate cancer in Sweden, we found that a significant proportion
      (26.6%) of affected men diagnosed died of their disease, which challenges earlier
      descriptions of incidental prostate cancer as a non-lethal disease.

PMID- 19088722
TI  - Breast cancer risks in women with a family history of breast or ovarian cancer
      who have tested negative for a BRCA1 or BRCA2 mutation.
AB  - Genetic testing for mutations in BRCA1 and BRCA2 is available in Canada for women
      with a significant family history of breast cancer. For the majority of tested
      women, a BRCA1 or BRCA2 mutation is not found, and counselling regarding breast
      cancer risk is based on the review of the pedigree. In this prospective study, we
      estimate breast cancer risks in women with a family history of breast cancer and
      for whom the proband tested negative for a mutation in BRCA1 or BRCA2. Families
      with two or more breast cancers under the age of 50 years, or with three cases of
      breast cancer at any age, and who tested negative for a BRCA1 or BRCA2 mutation
      were identified. Follow-up information on cancer status was collected on all
      first-degree relatives of breast cancer cases. The standardised incidence ratios
      (SIRs) for breast cancer were calculated by dividing the observed numbers of
      breast cancer by the expected numbers of breast cancers, based on the rates in
      the provincial cancer registries. A total of 1492 women from 365 families were
      included in the analyses. The 1492 first-degree relatives of breast cancer cases
      contributed 9109 person-years of follow-up. Sixty-five women developed breast
      cancer, compared to 15.2 expected number (SIR=4.3). The SIR was highest for women
      under the age of 40 (SIR=14.9) years and decreased with increasing age. However,
      the absolute risk was higher for women between the age of 50 and 70 (1% per year)
      years than for women between 30 and 50 (0.4% per year) years of age. There was no
      elevated risk for ovarian, colon or any other form of cancer. Women with a
      significant family history of breast cancer (ie, two or more breast cancers under
      the age of 50 years, or three or more breast cancers at any age), but who test
      negative for BRCA mutations have approximately a four-fold risk of breast cancer.
      Women in these families may be candidates for tamoxifen chemoprevention and/or
      intensified breast screening with an MRI.

PMID- 19088723
TI  - Cross talk of signals between EGFR and IL-6R through JAK2/STAT3 mediate
      epithelial-mesenchymal transition in ovarian carcinomas.
AB  - Epidermal growth factor receptor (EGFR) is overexpressed in ovarian carcinomas,
      with direct or indirect activation of EGFR able to trigger tumour growth. We
      demonstrate significant activation of both signal transducer and activator of
      transcription (STAT)3 and its upstream activator Janus kinase (JAK)2, in high
      grade ovarian carcinomas compared with normal ovaries and benign tumours. The
      association between STAT3 activation and migratory phenotype of ovarian cancer
      cells was investigated by EGF-induced epithelial-mesenchymal transition (EMT) in
      OVCA 433 and SKOV3 ovarian cancer cell lines. Ligand activation of EGFR induced a
      fibroblast-like morphology and migratory phenotype, consistent with the
      upregulation of mesenchyme-associated N-cadherin, vimentin and nuclear
      translocation of beta-catenin. This occurred concomitantly with activation of the
      downstream JAK2/STAT3 pathway. Both cell lines expressed interleukin-6 receptor
      (IL-6R), and treatment with EGF within 1 h resulted in a several-fold enhancement
      of mRNA expression of IL-6. Consistent with that, EGF treatment of both OVCA 433
      and SKOV3 cell lines resulted in enhanced IL-6 production in the serum-free
      medium. Exogenous addition of IL-6 to OVCA 433 cells stimulated STAT3 activation
      and enhanced migration. Blocking antibodies against IL-6R inhibited IL-6
      production and EGF- and IL-6-induced migration. Specific inhibition of STAT3
      activation by JAK2-specific inhibitor AG490 blocked STAT3 phosphorylation, cell
      motility, induction of N-cadherin and vimentin expression and IL6 production.
      These data suggest that the activated status of STAT3 in high-grade ovarian
      carcinomas may occur directly through activation of EGFR or IL-6R or indirectly
      through induction of IL-6R signalling. Such activation of STAT3 suggests a
      rationale for a combination of anti-STAT3 and EGFR/IL-6R therapy to suppress the
      peritoneal spread of ovarian cancer.

PMID- 19088724
TI  - A phase I trial of Capecitabine+Gemcitabine with radical radiation for locally
      advanced pancreatic cancer.
AB  - Standard chemoradiotherapy with infusional 5FU for locally advanced pancreatic
      cancer (LAPC) has limited efficacy in this disease. The combination of
      Capecitabine (Cap) and Gemcitabine (Gem) are synergistic and are potent
      radiosensitisers. The aim of this phase I trial was thus to determine the highest
      administered dose of the Cap plus Gem combination with radical radiotherapy (RT)
      for LAPC. Patients had LAPC, adequate organ function, ECOG PS 0-1. During RT, Gem
      was escalated from 20-50 mg m(-2) day(-1) (twice per week), and Cap 800-2000 mg
      m(-2) day(-1) (b.i.d, days 1-5 of each week). Radiotherapy 50.4 Gy/28
      fractions/5.5 weeks, using 3D-conformal techniques. Three patients were entered
      to each dose level (DL). Dose-limiting toxicity(s) (DLTs) were based on treatment
      related toxicities. Twenty patients were accrued. Dose level (DL) 1: Cap/Gem;
      800/20 mg m(-2) day(-1) (3 patients), DL2: 1000/20 (12 patients), DL3: 1300/30 (5
      patients). Dose-limiting toxicities were observed in DL3; grade 3 dehydration (1
      patient) and grade 3 diarrhoea and dehydration (1 patient). Dose level 2 was the
      recommend phase 2 dose. Disease control rate was 75%: PR=15%, SD=60%. Median
      overall survival was 11.2 months. The addition of Cap and Gem to radical RT was
      feasible and active and achieved at relatively low doses.

PMID- 19088725
TI  - Reversibility of apoptosis in cancer cells.
AB  - Apoptosis is a cell suicide programme characterised by unique cellular events
      such as mitochondrial fragmentation and dysfunction, nuclear condensation,
      cytoplasmic shrinkage and activation of apoptotic protease caspases, and these
      serve as the noticeable apoptotic markers for the commitment of cell demise.
      Here, we show that, however, the characterised apoptotic dying cancer cells can
      regain their normal morphology and proliferate after removal of apoptotic
      inducers. In addition, we demonstrate that reversibility of apoptosis occurs in
      various cancer cell lines, and in different apoptotic stimuli. Our findings show
      that cancer cells can survive after initiation of apoptosis, thereby revealing an
      unexpected potential escape mechanism of cancer cells from chemotherapy.

PMID- 19088728
TI  - Diabetes and aspirin: beware of underpowered negative trials.

PMID- 19088729
TI  - A case of coronary artery fistula visualized by 64-slice multidetector CT.
AB  - BACKGROUND: A 27-year-old woman was admitted to hospital with a 1-year history of
      mild dyspnea. INVESTIGATIONS: Physical examination, chest radiography,
      electrocardiography, transthoracic echocardiography, 64-slice multidetector CT
      and coronary angiography. DIAGNOSIS: Fistula originating from the left anterior
      coronary artery and draining into the right ventricle, in conjunction with an
      aneurysm of the left anterior descending artery. MANAGEMENT: Surgical closure of
      the fistula using normothermic cardiopulmonary bypass.

PMID- 19088730
TI  - New challenges for a new leader.

PMID- 19088731
TI  - Signaling to gene expression: calcium, calcineurin and NFAT.

PMID- 19088733
TI  - Spotlight on IL-22-producing NK cell receptor-expressing mucosal lymphocytes.
AB  - New findings show that a subpopulation of mucosal ROR gammat+ cells expresses
      natural killer cell receptors and produces interleukin 22. These innate immune
      cells may be pivotal in maintaining mucosal homeostasis.

PMID- 19088734
TI  - From immunity to tolerance through HDAC.
AB  - Regulation of expression of the gene encoding interleukin 10 by the histone
      deacetylase HDAC11 emphasizes the ability of an antigen-presenting cell to induce
      immunity or tolerance in CD4+ T cells.

PMID- 19088735
TI  - Rules to 'prime' by.
AB  - A systems biology approach provides correlates of successful vaccination, which
      allows a new method for measuring early vaccine efficiency and suggests
      hypotheses for the mechanisms that underlie immunogenicity.

PMID- 19088736
TI  - A new function for the RNA-editing enzyme ADAR1.
AB  - ADAR1 catalyzes the deamination of adenosine to inosine in double-stranded RNA.
      This RNA-editing enzyme is now shown to be involved in hematopoiesis, where it
      acts to suppress interferon signaling and to block premature apoptosis.

PMID- 19088738
TI  - Calcium signaling in immune cells.
AB  - Calcium acts as a second messenger in many cell types, including lymphocytes.
      Resting lymphocytes maintain a low concentration of Ca2+. However, engagement of
      antigen receptors induces calcium influx from the extracellular space by several
      routes. A chief mechanism of Ca2+ entry in lymphocytes is through store-operated
      calcium (SOC) channels. The identification of two important molecular components
      of SOC channels, CRACM1 (the pore-forming subunit) and STIM1 (the sensor of
      stored calcium), has allowed genetic and molecular manipulation of the SOC entry
      pathway. In this review, we highlight advances in the understanding of Ca2+
      signaling in lymphocytes with special emphasis on SOC entry. We also discuss
      outstanding questions and probable future directions of the field.

PMID- 19088739
TI  - Two variants in Ankyrin 3 (ANK3) are independent genetic risk factors for bipolar
      disorder.
AB  - Two recent reports have highlighted ANK3 as a susceptibility gene for bipolar
      disorder (BD). We first reported association between BD and the ANK3 marker
      rs9804190 in a genome-wide association study (GWAS) of two independent samples
      (Baum et al., 2008). Subsequently, a meta-analysis of GWAS data based on samples
      from the US and the UK reported association with a different ANK3 marker,
      rs10994336 (Ferreira et al., 2008). The markers lie about 340 kb apart in the
      gene. Here, we test both markers in additional samples and characterize the
      contribution of each marker to BD risk. Our previously reported findings at
      rs9804190, which had been based on DNA pooling, were confirmed by individual
      genotyping in the National Institute of Mental Health (NIMH) waves 1-4 (P=0.05;
      odds ratio (OR)=1.24) and German (P=0.0006; OR=1.34) samples. This association
      was replicated in an independent US sample known as NIMH wave 5 (466 cases, 212
      controls; P=0.017; OR=1.38). A random-effects meta-analysis of all three samples
      was significant (P=3 x 10(-6); OR=1.32), with no heterogeneity. Individual
      genotyping of rs10994336 revealed a significant association in the German sample
      (P=0.0001; OR=1.70), and similar ORs in the NIMH 1-4 and NIMH 5 samples that were
      not significant at the P<0.05 level. Meta-analysis of all three samples supported
      an association with rs10994336 (P=1.7 x 10(-5); OR=1.54), again with no
      heterogeneity. There was little linkage disequilibrium between the two markers.
      Further analysis suggested that each marker contributed independently to BD, with
      no significant marker x marker interaction. Our findings strongly support ANK3 as
      a BD susceptibility gene and suggest true allelic heterogeneity.

PMID- 19088740
TI  - An analysis of regional microvascular loss and recovery following two grades of
      fluid percussion trauma: a role for hypoxia-inducible factors in traumatic brain
      injury.
AB  - Secondary hypoxic/ischemic injuries, stemming from reductions in cerebral blood
      flow are important contributing factors in progressive neuronal dysfunction after
      brain trauma. A greater preclinical understanding of how brain trauma leads to
      secondary hypoxia/ischemia is necessary in the development of posttraumatic brain
      injury (TBI) therapeutics. To this end, we examined the density of microvascular
      coverage in the injured and contralateral cortical hemispheres using two
      intensities of fluid percussion trauma in rats. A silicone microangiography
      technique showed a significant loss in microvascular density in 2 atmosphere
      (atm) (16.9+/-3.8%) and 3 atm (15.7+/-1.3%) injured animals relative to sham
      animals (29.9+/-2.5%; P<0.01). RECA-1 immunohistochemistry indicated that
      capillary changes involved a reduction in capillary number and diameter.
      Reduction in microvascular density was shown to be a diffuse phenomenon occurring
      up to 4 mm rostral and caudal to the injury epicenter. Recovery of
      microvasculature occurred by 2 weeks after injury only in the 2 atm injury group.
      Expression of HIF1alpha and increased vascular endothelial growth factor
      expression were observed in the ipsilateral hippocampus suggesting sufficiently
      impaired microcirculation resulting in the expression of hypoxic-response
      proteins. Collectively, the results indicate diffuse and heterogeneous
      microvascular alterations as well as endogenous expression of neuroprotective and
      neovascularization pathways after TBI.

PMID- 19088741
TI  - Dopamine release in the human striatum: motor and cognitive tasks revisited.
AB  - Striatal dopamine (DA) release has been shown during behavioural tasks, but the
      relative contribution of motor, reward, and cognitive components is unclear.
      Dopamine release was quantified using [(11)C]-raclopride in two studies using a
      triple-scan approach, comprising active task, motor control, and rest. In the
      first, bolus radiotracer was delivered during a sequential motor learning
      paradigm; in the second, a spatial planning task, bolus plus constant infusion
      was applied. [(11)C]-raclopride binding potentials (BP(ND)s) in striatal
      functional subdivisions were compared across conditions. [(11)C]-raclopride
      BP(ND) was significantly reduced in active task compared with rest in both the
      sensorimotor and associative striatum in both studies, because of differences
      between rest and motor control conditions. In both regions, the motor control
      BP(ND) fell between the rest and active task in the planning study, but the
      difference between motor control and active task conditions was not significant.
      No such changes were observed in the limbic striatum. Using rigorous methodology,
      this study validates earlier evidence that striatal DA release occurs during
      behavioural challenges. Increased DA release during movement was reliably
      detected in the sensorimotor and associative striatum, supporting use of the
      functional subdivision model in humans. No additional DA release was observed
      specific to the cognitive component of either task.

PMID- 19088742
TI  - Reperfusion-induced temporary appearance of therapeutic window in penumbra after
      2 h of photothrombotic middle cerebral artery occlusion in rats.
AB  - To explore the effects of reperfusion on evolution of focal ischemic injury,
      spontaneously hypertensive male rats were subjected to photothrombotic distal
      middle cerebral artery occlusion (MCAO) with or without YAG laser-induced
      reperfusion. The volume of fodrin breakdown zone, water content, and brain tissue
      levels of sodium (Na(+)) and potassium (K(+)) were measured in the ischemic core
      and penumbra. Reperfusion attenuated fodrin breakdown, and the volume containing
      fodrin breakdown product at 3 h after reperfusion (5 h after MCAO) (30+/-7 mm(3))
      was significantly smaller than the 42+/-3 mm(3) of the permanent occlusion group.
      After 3 to 6 h of ischemia, Na(+) increased, and K(+) decreased in the ischemic
      core. Reperfusion after 2 h of MCA occlusion did not mitigate the ischemia
      induced changes in brain tissue electrolytes and water content at 3 to 6 h of
      ischemia. Even in reperfusion after comparatively long periods of occlusion where
      brain infarction size, assessed 3 days after MCAO, was not significantly reduced
      by reperfusion, and the precipitating indicators of the ischemic core (Na(+),
      K(+), water content) did not improve, temporary improvement or a delay in
      progression of ischemic injury was discernible in the penumbra. These results
      indicate the possibility that treatment with reperfusion is permissive to the
      effects of neuroprotection.

PMID- 19088743
TI  - Genetics of speciation.

PMID- 19088744
TI  - [Apoptosis induced by granzyme B].
AB  - Results of biochemical studies of apoptosis reactions induced by granzyme B are
      considered and summarized. Special attention is paid to the reactions of
      procaspase activation and limited proteolysis of apoptotic targets. Found values
      of kinetic constants of granzyme B-mediated enzymatic reactions are listed.

PMID- 19088745
TI  - [Neuro- and psychotropic activity of N-uronoylamino acids and N-uronoylpeptides].
AB  - Peculiarities of rat behavior were studied on a series of experimental stress
      models after systemic administration of new N-uronoyl derivatives of amino acids.
      The psychotropic effect was shown to be determined by the nature of the amino
      acid fragment. N-(l,2:3,4-di-O-isopropylidene-alpha-D-galactopyranuronoyl)
      glycylglycine exhibited a more pronounced anxiolytic effect than pyracetam,
      whereas N-(l,2:3,4-di-O-isopropylidene-alpha-D-galactopyranuronoyl)
      glycylglutamic acid is a stronger antidepressant than amitriptyline. Mechanisms
      of the psychotropic effects of the examined derivatives are discussed.

PMID- 19088746
TI  - [Selective inhibitors of plasmepsin II from Plasmodium falciparum based on
      pepstatin].
AB  - A number of new inhibitors of plasmepsin II (PlmII) from Plasmodium falciparum,
      one of the key factors of malarial parasite survival, were synthesized. The
      inhibitors are analogues of pepstatin with various variants of Ala residue
      substitutions. Effects of the inhibitors on human PlmII and cathepsin D were
      studied. Inhibition of PlmII by the substrate was found, which required the use
      of the modified Henderson method for the determination of inhibition constants.
      Two synthesized inhibitors were shown to exhibit a pronounced selectivity to
      PlmII (K(i) = 5.5 and 5 nM) in comparison with cathepsin D (K(i) = 230 and 3000
      nM, respectively).

PMID- 19088747
TI  - [Identification of proteins in complexes with alpha-latrotoxin receptors].
AB  - A thorough analysis of proteins capable of interacting with presynaptic receptors
      of alpha-latrotoxin was carried out. The protein components of receptor complexes
      were isolated from rat brain membranes by affinity chromatography on immobilized
      alpha-latrotoxin and antibodies to the cytoplasmic moiety of the calcium
      independent receptor of alpha-latrotoxin (CIRL) followed by analysis by mass
      spectrometry. Several proteins were identified, with structural proteins,
      intracellular signal proteins, and proteins involved in the endocytosis and
      transport of synaptic vesicles being among them.

PMID- 19088748
TI  - [Production of monoclonal antibodies to the prion protein and their
      characterization].
AB  - Antibodies to the prion protein (PrP), particularly, monoclonal antibodies, are
      necessary tools in the diagnostics and study of prion diseases and potential
      means of their immunotherapy. For the production of monoclonal antibodies, BALB/c
      mice were immunized by a recombinant bovine PrP. Three stable hybridomas
      producing antibodies of IgM class were prepared. The antibodies were bound to PrP
      in a solid-phase enzyme immunoassay and immunoblotting. The epitope mapping
      accomplished with the use of synthetic peptides showed that an epitope located in
      region 25-36 of PrP corresponds to one antibody, and epitopes located in region
      222-229, to the other two. The antibodies to fragment 222-229 purified by
      affinity chromatography recognized with a high specificity conglomerates of a
      pathogenic prion in the brain tissue of cows suffering from spongiform
      encephalopathy. Thus, in nontransgenic mice, PrP-specific monoclonal antibodies
      were produced, useful in studies and diagnostics of prion diseases.

PMID- 19088749
TI  - [Carbon dioxide of air inhibits the formation of silver nanoparticles initiated
      by proteins in polyacrylamide gel and in solution].
AB  - It was shown that the detection of proteins in polyacrylamide gel by silver is
      inhibited by contact with air of the ammonia complex with silver ions used at the
      first stage of detection. It was proved by experiments on the reduction of silver
      by ethanolamine from a complex with ethanolamine and by formaldehyde from a
      complex with ammonia that the formation of silver nanoparticles initiated by
      proteins is inhibited by air carbon dioxide. The participation of carbon dioxide
      in this process is discussed. It was found that even the breathing of an
      experimenter can induce variations in carbon dioxide concentration sufficient to
      adversely affect the reproducibility of the silver staining techniques. It was
      concluded that, for stable staining of proteins by silver in polyacrylamide gel,
      it is necessary to maintain a low concentration of carbon dioxide in air over the
      detection solutions.

PMID- 19088751
TI  - [7-aminoactinomycin as a fluorescent probe for DNA unwinding and denaturation].
AB  - A fluorescent analogue of the antibiotic actinomycin D, 7-aminoactinomycin D
      (7AAMD), which is widely used in molecular biology, was shown by steady-state,
      polarization, and phase fluorescent spectroscopy to bind primarily in unwound
      regions of DNA with a concomitant increase in its emission intensity. The maximum
      emission intensity of 7AAMD is observed for denatured DNA. Thus, 7AAMD may serve
      as a good indicator of DNA unwinding, denaturation, and fragmentation.

PMID- 19088750
TI  - [Protein S3 fragments neighboring mRNA during elongation and translation
      termination on the human ribosome].
AB  - Protein S3 fragments were determined that crosslink to modified mRNA analogues in
      positions +5 to +12 relative to the first nucleotide in the P-site binding codon
      in model complexes mimicking states of ribosomes at the elongation and
      translation termination steps. The mRNA analogues contained a Phe codon UUU/UUC
      at the 5'-termini that could predetermine the position of the tRNA(Phe) on the
      ribosome by the location of P-site binding and perfluorophenylazidobenzoyl group
      at a nucleotide in various positions 3' of the UUU/UUC codon. The crosslinked S3
      protein was isolated from 80S ribosomal complexes irradiated with mild UV light
      and subjected to cyanogen bromide-induced cleavage at methionine residues with
      subsequent identification of the crosslinked oligopeptides. An analysis of the
      positions of modified oligopeptides resulting from the cleavage showed that, in
      dependence on the positions of modified nucleotides in the mRNA analogue, the
      crosslinking sites were found in the N-terminal half of the protein (fragment 2
      127) and/or in the C-terminal fragment 190-236; the latter reflects a new
      peculiarity in the structure of the mRNA binding center in the ribosome, unknown
      to date. The results of crosslinking did not depend on the type of A-site codon
      or on the presence of translation termination factor eRF1.

PMID- 19088752
TI  - [Effect of a modification of the processing site of Bacillus intermedius glutamyl
      endopeptidase on the production of active enzyme by Bacillus subtilis cells].
AB  - A site-directed modification in position P1 of the processing site of Bacillus
      intermedius glutamyl endopeptidase was carried out. Variants of the protease gene
      were obtained that correspond to the protein with an Ala, Asn, Ser, or Glu
      residue in this position substituted for the Lys residue. The residue in the P1
      position of the processing site was shown to affect substantially the production
      of the active enzyme; however, none of the mutations leads to the complete
      termination of active protein production by cells.

PMID- 19088753
TI  - [A highly sensitive and rapid method for the detection of DNA fragments using the
      photoprotein obelin as a reporter].
AB  - The recombinant Ca2+-activated photoprotein obelin was used as a reporter protein
      in a solid-phase bioluminescent hybridization DNA assay. Oligonucleotide probes
      were immobilized on the surface of a fine-grained polymer or microbiological
      plates of different types. A 30-mer oligonucleotide or its derivative with a
      biotin residue on the 3'-terminus, as well as a denatured double-stranded PCR
      fragment of the hepatitis C virus with the sequence of the 30-mer
      oligonucleotide, was used as a DNA template. The probe in the hybridization
      complex was labeled by elongation of the chain using Taq DNA polymerase in the
      presence of biotinylated deoxyuridine triphosphate. The results of the
      bioluminescent assay were compared with the results of colorimetric analysis
      obtained with alkaline phosphatase as a reporter protein. It was shown that the
      use of the bioluminescent obelin label substantially accelerates the DNA
      detection procedure, ensures a high sensitivity of the assay (no less than 10(
      15) mol of DNA template), and enables quantitative determination of the amount of
      DNA template in the tested sample.

PMID- 19088754
TI  - [FLASH-PCR diagnostics of toxigenic fungi of the genus Fusarium].
AB  - A test system for the diagnostics and identification of seven toxigenic fungi
      causing fusarioses of cereals (Fusarium graminearum, F. culmorum, F. poae, F.
      sporotrichioides, F. langsethiae, F. avenaceum, and F. tricinctum) was developed
      using PCR. The identification of pathogen is based on the specific amplification
      of a DNA fragment of the gene of translation elongation factor 1 alpha (tef
      1alpha) and subsequent detection of the results by the fluorescent amplification
      based specific hybridization method. The system was tested on 38 isolates of
      different fungi of the genus Fusarium.

PMID- 19088755
TI  - [Structures of O-polysaccharides from two Shigella dysenteriae type 8 strains].
AB  - The structure of the O-polysaccharide (O-antigen) from Shigella dysenteriae type
      8 bacteria (strain 599) was corrected using modern NMR techniques (structure 1).
      The revisions concerned the position of the Glc residue (in the main, but not the
      side, chain), the site of its substitution, and the configuration of the O
      glycoside linkage of the GlcNAc residue. The S. dysenteriae type 8 bacterium
      (strain G1221), the second investigated representative, was found to produce
      another structural variant of the O-polysaccharide. It contains GlcNAc instead of
      the Glc residue in the main chain (structure 2). This data may lead to approval
      of division of S. dysenteriae type 8 into two subtypes: [Formula: see text].

PMID- 19088756
TI  - [Synthesis of heteroaromatic N-beta-glycosides of N-acetylglucosamine under phase
      transfer conditions: II].
AB  - Regioselective N-beta-glucosamination of various unsubstituted or C4-, C5-, or C6
      monosubstituted indolin-2-ones under phase transfer conditions was studied. The
      regioselectivity was unambiguously proved by (1)H NMR spectroscopy and X-ray
      analysis. The presence of a substituent at C7 of the aromatic ring leads to the
      formation of either a mixture of isomeric N-beta- and O-beta-D-glucosaminides or
      only oxazoline and/or 2-acetamidoglycal irrespective of the reaction conditions.

PMID- 19088757
TI  - [Synthesis of acetal and phosphocyclic methriolipids].
AB  - The first representatives of acetal and phosphocyclic lipids based on methriol (2
      hydroxymethyl-2-methyl-1,3-propanediol) were synthesized. The interaction of the
      starting triol with higher aldehydes gave the corresponding alkylidene compounds,
      which were subsequently phosphorylated by derivatives of phosphorous acid. The
      intermediate amidophosphites were treated without isolation with iodobenzene,
      sulfur, or selenium to give phosphoacetals and their thio- and selenoanalogues,
      which are acetal phospholipids. Methriol bicyclophosphite was also used in the
      lipid synthesis. It was acylated with palmitoyl chloride at one of the bicyclic
      oxygen atoms. Alcoholysis of acyl polyol chlorophosphite resulted in a
      phospholipid, which was oxidized with sulfur to give thionphosphate.

PMID- 19088758
TI  - [Synthesis and cytotoxicity of novel phosphorusless analogues of edelfosine].
AB  - Modified series of phosphorusless edelfosine analogues bearing the polar heads of
      aliphatic bases, N,N-dimethylethanolamine and N,N,N(1),N(1)
      tetramethylethylenediamine, were synthesized, with the length of the spacer
      varying from three to four methylene units. The cytotoxic characteristics of the
      compounds synthesized were studied.

PMID- 19088759
TI  - [New derivatives of eremomycin containing (15)n or f atoms for NMR study].
AB  - New semisynthetic derivatives of eremomycin containing (15)N or F atom were
      obtained for studying the antibiotic-target interaction in intact cells of Gram
      positive bacteria by REDOR NMR method. Interaction of the terminal carboxyl group
      of amino acid 7 (AA7) of eremomycin with amines in the presence of PyBOP and TBTU
      reagents resulted in the corresponding [(15)N]-amide, p-fluorobenzylamide, p
      fluorophenylpiperazide, and 6-N-(p-fluorobenzyl)aminohexylamide. A selective
      method of [(15)N]-amidation of carboxyl group of amino acid 3 (AA3) of
      carboxyeremomycin was developed, and the amide of eremomycin containing [(15)N]
      in AA3 amide group near the antibiotic binding pocket was obtained.
      Carboxyeremomycin bisamides substituted at AA3 and AA7 and containing two atoms
      of [(15)N] or F were obtained from carboxyeremomycin and [(15)N]NH4Cl or the
      corresponding p-fluorobenzylamine hydrochloride in the presence of PyBOP at pH
      ~8. The Edman degradation of eremomycin p-fluorobenzylamide gave de-(D-MeLeu)
      eremomycin p-fluorobenzylamide, a hexapeptide derivative incapable of the
      antibiotic binding with -D-Ala-D-Ala fragment of growing cell wall peptidoglycan.
      Among the compounds studied, carboxyeremomycin bis-p-fluorobenzylamide showed the
      best activity against both the glycopeptides-sensitive and glycopeptides
      resistant strains of staphylococci and enterococci.

PMID- 19088760
TI  - [(22R,23R)-3beta-Hydroxy-22,23-epoxy-5alpha-ergost-8(14)-en-15-one: improved
      synthesis and toxicity to MCF-7 cells].
AB  - The chemical synthesis of (22R,23R)-3beta-hydroxy-22,23-epoxy-5alpha-ergost-8(14)
      en-15-one from (22E)-3beta-acetoxy-5alpha-ergosta-7,14,22-triene was improved.
      The stages of obtaining and isomerizing (22E)-3beta-acetoxy-14alpha,15alpha-epoxy
      5alpha-ergosta-7,22-diene were optimized. The introduction of the (22R,23R)
      epoxide cycle was carried out by a basic treatment of intermediate (22S,23R)
      3beta,23-diacetoxy-22-iodo-5alpha-ergost-8(14)-en-15-one. In cells of human
      mammary gland carcinoma MCF-7 (22R,23R)-3beta-hydroxy-22,23-epoxy-5alpha-ergost
      8(14)-en-15-one showed a high toxicity (TC(50) = 0.4 +/- 0.1 microM for 48-h
      incubation in serum-free medium).

PMID- 19088761
TI  - [Synthesis of tetrasubstituted porphyrins by interaction of 5-aryldipyrromethanes
      with 4-substituted benzaldehydes].
AB  - Synthesis of tetraphenyl-substituted porphyrins with tret-butyl and
      methoxycarbonyl groups in meso-aryl radicals is described. It is shown that,
      during the condensation of dipyrromethanes with substituted benzaldehydes, a
      rearrangement occurs with the formation of a mixture of isomeric porphyrins. The
      character of these rearrangements depends on the position of substituents in the
      starting compounds.

PMID- 19088762
TI  - [A new mutation c.422C>G (p.S141C) in homo- and heterozygous forms of the human
      leptin gene].
AB  - Mutation g.15409C>G, c.422C>G (p.S141C) in homo- and heterozygous forms of the
      human LEP gene was identified among some patients of the high mountain village of
      Karaul, Ashkhabad oblast, Turkmenistan, some of which suffer from adiposity. It
      causes the substitution S120C in the secreted leptin. The mature leptin molecule
      (146 aa) has only two Cys residues (C96 and C146) forming an S-S bridge, which is
      important for the hormone function. A third mutation, C120, in the molecule might
      disturb the correct formation of the S-S bond and could alter the leptin
      activity.

PMID- 19088763
TI  - Plasma deuterium oxide accumulation following ingestion of different carbohydrate
      beverages.
AB  - Optimal fluid delivery from carbohydrate solutions such as oral rehydration
      solutions or sports drinks is essential. The aim of the study was to investigate
      whether a beverage containing glucose and fructose would result in greater fluid
      delivery than a beverage containing glucose alone. Six male subjects were
      recruited (average age (+/-SD): 22 +/- 2 y). Subjects entered the laboratory
      between 0700 h and 0900 h after an overnight fast. A 600 mL bolus of 1 of the 3
      experimental beverages was then given. The experimental beverages were water (W),
      75 g glucose (G), or 50 g glucose and 25 g fructose (GF); each beverage also
      contained 3.00 g of D2O. Following administration of the experimental beverage
      subjects remained in a seated position for 180 min. Blood and saliva samples were
      then taken every 5 min in the first hour and every 15 min thereafter. Plasma and
      saliva samples were analyzed for deuterium enrichment by isotope ratio mass
      spectrometry. Deuterium oxide enrichments were compared using a 2-way repeated
      measures analysis of variance. The water trial (33 +/- 3 min) showed a
      significantly shorter time to peak than either G (82 +/- 40 min) or GF (59 +/- 25
      min), but the difference between G and GF did not reach statistical significance.
      There was a significantly greater AUC for GF (55 673 +/- 10 020 delta per
      thousand vs. Vienna Standard Mean Ocean Water (VSMOW).180 min) and W (60 497 +/-
      9864 delta per thousand vs. VSMOW.180 min) compared with G (46 290 +/- 9622 delta
      per thousand vs. VSMOW.180 min); W and GF were not significantly different from
      each other. These data suggest that a 12.5% carbohydrate beverage containing
      glucose and fructose results in more rapid fluid delivery in the first 75 min
      than a beverage containing glucose alone.

PMID- 19088764
TI  - Endothelial cell-derived nitric oxide mobilization is attenuated in copper
      deficient rats.
AB  - The attenuation of endothelium-dependent nitric oxide (NO) mediated vasodilation
      is a consistent finding in both conduit and resistance vessels during dietary
      copper (Cu) deficiency. Although the effect is well established, evidence for the
      mechanism remains circumstantial. This study was designed to determine the
      relative amount of NO produced in and released from the vascular endothelium.
      Using the fluorescent NO indicator, 4-amino-5-methylamino-2',7'
      difluorofluorescein (DAF-FM), we now demonstrate the effect of a Cu-deficient
      diet on the production of NO from the endothelium of resistance arterioles. In
      one group of experiments, control and Cu-chelated lung microvascular endothelial
      cells (ECs) were used to assay NO production and fluorescence was observed by
      confocal microscopy. Weanling Sprague-Dawley rats were fed purified diets that
      were either Cu adequate (6.3 micrograms Cu per gram of food) or Cu deficient (0.3
      micrograms Cu per gram of food) for 4 weeks. In the second series of experiments,
      first-order arterioles were microsurgically isolated from the rat cremaster
      muscle, cannulated, and pressurized with (3[N-morpholino]propanesulfonic acid)
      physiologic salt solution (MOPS-PSS). DAF-FM (5 micromol.L-1) was added in the
      lumen of the vessel to measure NO release. Baseline DAF-FM fluorescence was
      significantly lower in Cu-chelated ECs than in controls. In response to 10-6
      mol.L-1 acetylcholine, fluorescent intensity was significantly less in chelated
      ECs and in the lumen of Cu-deficient arterioles. The results suggest that
      production and release of NO by the vascular endothelium is inhibited by a
      restriction of Cu. This inhibition may account for the attenuated vasodilation
      previously reported in Cu-deficient rats.

PMID- 19088765
TI  - Caffeine and carbohydrate supplementation during exercise when in negative energy
      balance: effects on performance, metabolism, and salivary cortisol.
AB  - The ingestion of carbohydrate (+CHO) and caffeine (+CAF) during exercise is a
      commonly used ergogenic practice. Investigations are typically conducted with
      subjects who are in a rested state after an overnight fast. However, this state
      of positive energy balance is not achieved during many work and exercise
      circumstances. The aim of this study was to evaluate the substrate use and
      performance effects of caffeine and carbohydrate consumed alone and in
      combination while participants were in negative energy balance. Male participants
      (n = 9; 23 +/- 3 years; 74.1 +/- 10.6 kg) completed 4 trials in random order: 
      CAF/-CHO, -CAF/+CHO, +CAF/-CHO, and +CAF/+CHO. Diet and exercise were prescribed
      for 2 days before each trial to ensure negative energy balance. For each trial,
      before and after 2 h of cycling at 50% of maximal watts, a saliva sample and a
      muscle biopsy (vastus lateralis) were obtained. A simulated 20 km time trial was
      then performed. The respiratory exchange ratio was higher (p < 0.05) in +CHO
      trials and lower (p < 0.05) in the +CAF/+CHO trial than in the -CAF/+CHO trial.
      Salivary cortisol response was higher (p < 0.05) in the +CAF/-CHO trial than in
      any of the other trials. Muscle glycogen and heart rates were similar in all
      trials. Performance in the 20 km time trial was better in the -CAF/+CHO trial
      than in the -CAF/-CHO trial (p < 0.05), but the +CAF/+CHO trial was no better
      than the +CAF/-CHO trial (p > 0.05), or any of the other trials. When co-ingested
      with carbohydrate, caffeine increased fat use and decreased nonmuscle glycogen
      carbohydrate use over carbohydrate alone when participants are in negative energy
      balance; however, caffeine had no effect on the 20 km cycling time trial
      performance.

PMID- 19088766
TI  - Vastus lateralis surface and single motor unit EMG following submaximal
      shortening and lengthening contractions.
AB  - A single shortening contraction reduces the force capacity of muscle fibers,
      whereas force capacity is enhanced following lengthening. However, how motor unit
      recruitment and discharge rate (muscle activation) are adapted to such changes in
      force capacity during submaximal contractions remains unknown. Additionally,
      there is limited evidence for force enhancement in larger muscles. We therefore
      investigated lengthening- and shortening-induced changes in activation of the
      knee extensors. We hypothesized that when the same submaximal torque had to be
      generated following shortening, muscle activation had to be increased, whereas a
      lower activation would suffice to produce the same torque following lengthening.
      Muscle activation following shortening and lengthening (20 degrees at 10 degrees
      /s) was determined using rectified surface electromyography (rsEMG) in a 1st
      session (at 10% and 50% maximal voluntary contraction (MVC)) and additionally
      with EMG of 42 vastus lateralis motor units recorded in a 2nd session (at 4%
      47%MVC). rsEMG and motor unit discharge rates following shortening and
      lengthening were normalized to isometric reference contractions. As expected,
      normalized rsEMG (1.15 +/- 0.19) and discharge rate (1.11 +/- 0.09) were higher
      following shortening (p < 0.05). Following lengthening, normalized rsEMG (0.91 +/
      0.10) was, as expected, lower than 1.0 (p < 0.05), but normalized discharge rate
      (0.99 +/- 0.08) was not (p > 0.05). Thus, muscle activation was increased to
      compensate for a reduced force capacity following shortening by increasing the
      discharge rate of the active motor units (rate coding). In contrast, following
      lengthening, rsEMG decreased while the discharge rates of active motor units
      remained similar, suggesting that derecruitment of units might have occurred.

PMID- 19088767
TI  - Conjugated linoleic acid prevents growth attenuation induced by corticosteroid
      administration and increases bone mineral content in young rats.
AB  - Corticosteroids are a common therapy in many disease states, despite frequent and
      potentially serious side effects. Nutritional supplementation with conjugated
      linoleic acid (CLA) has been shown to increase fat-free mass, whereas
      supplementation with n-3 and n-6 fatty acids has been shown to increase bone
      mineral density (BMD). To determine whether CLA can attenuate the side effects of
      8 weeks of corticosteroid administration, we randomized twenty-four 5-week-old
      male Sprague-Dawley rats into 1 of 4 groups: control; control +
      methylprednisolone (7 mg.kg-1.week-1); CLA diet (1% CLA w/w); or CLA plus
      methylprednisolone. Body composition, bone mineral content (BMC), and BMD were
      assessed with dual-energy X-ray absorptiometry at the onset and at the end of the
      8-week intervention. The mechanical properties of bone were determined using 3
      point femur bending at the end of the intervention. Methylprednisolone resulted
      in an attenuation of the increase in body mass and lean mass over the 8 weeks (p
      < 0.05). CLA prevented the methylprednisolone-induced attenuation of body mass
      and lean mass accumulation. CLA also resulted in a greater increase in BMC (p <
      0.05) in the lumbar spine. The energy at failure of the isolated femurs was
      increased with CLA (p < 0.05). Dietary CLA prevents many of the growth- and bone
      related side effects arising from 8 weeks of corticosteroid administration,
      results in greater increases in BMC and BMD, and can contribute to an improvement
      in some of the mechanical properties of bone.

PMID- 19088768
TI  - Critical power in adolescent boys and girls--an exploratory study.
AB  - The purpose of the study was to identify critical power (CP) in boys and girls
      and to examine the physiological responses to exercise at and 10% above CP
      (CP+10%) in a sub-group of boys. Nine boys and 9 girls (mean age 12.3 (0.5) y
      performed 3 constant-load tests to derive CP. Eight of the boys then exercised,
      in random order, at CP and CP+10% until volitional exhaustion. CP was 123 (28)
      and 91 (26) W for boys and girls, respectively (p < 0.02), which was equivalent
      to 75 (6) and 72 (10) % of peak oxygen uptake, respectively (p > 0.47). Boys'
      time to exhaustion at CP was 18 min 37 s (4 min 13 s), which was significantly
      longer (p < 0.007) than that at CP+10% (9 min 42 s (2 min 31 s)). End-exercise
      values for blood lactate concentration (B[La]) and maximal oxygen uptake were
      higher in the CP+10% trial (5.0 (2.4) mmol.L-1 and 2.15 (0.4) L.min-1,
      respectively) than in the CP trial, (B[La], 4.7 (2.1) mmol.L-1; maximal oxygen
      uptake, 2.05 (0.35) L.min-1; p > 0.13). Peak oxygen uptake (expressed as a
      percentage of the peak value) was not attained at the end of the trials (94 (12)
      and 98 (14) % for CP and CP+10%, respectively). These results provide information
      about the boundary between the heavy and severe exercise intensity domains in
      children, and have demonstrated that CP in a group of boys does not represent a
      sustainable steady-state intensity of exercise.

PMID- 19088769
TI  - High-intensity aerobic interval training increases fat and carbohydrate metabolic
      capacities in human skeletal muscle.
AB  - High-intensity aerobic interval training (HIIT) is a compromise between time
      consuming moderate-intensity training and sprint-interval training requiring all
      out efforts. However, there are few data regarding the ability of HIIT to
      increase the capacities of fat and carbohydrate oxidation in skeletal muscle.
      Using untrained recreationally active individuals, we investigated skeletal
      muscle and whole-body metabolic adaptations that occurred following 6 weeks of
      HIIT (~1 h of 10 x 4 min intervals at ~90% of peak oxygen consumption (VO2 peak),
      separated by 2 min rest, 3 d.week-1). A VO2 peak test, a test to exhaustion (TE)
      at 90% of pre-training VO2 peak, and a 1 h cycle at 60% of pre-training VO2 peak
      were performed pre- and post-HIIT. Muscle biopsies were sampled during the TE at
      rest, after 5 min, and at exhaustion. Training power output increased by 21%, and
      VO2 peak increased by 9% following HIIT. Muscle adaptations at rest included the
      following: (i) increased cytochrome c oxidase IV content (18%) and maximal
      activities of the mitochondrial enzymes citrate synthase (26%), beta-hydroxyacyl
      CoA dehydrogenase (29%), aspartate-amino transferase (26%), and pyruvate
      dehydrogenase (PDH; 21%); (ii) increased FAT/CD36, FABPpm, GLUT 4, and MCT 1 and
      4 transport proteins (14%-30%); and (iii) increased glycogen content (59%). Major
      adaptations during exercise included the following: (i) reduced glycogenolysis,
      lactate accumulation, and substrate phosphorylation (0-5 min of TE); (ii)
      unchanged PDH activation (carbohydrate oxidation; 0-5 min of TE); (iii) ~2-fold
      greater time during the TE; and (iv) increased fat oxidation at 60% of pre
      training VO2 peak. This study demonstrated that 18 h of repeated high-intensity
      exercise sessions over 6 weeks (3 d.week-1) is a powerful method to increase
      whole-body and skeletal muscle capacities to oxidize fat and carbohydrate in
      previously untrained individuals.

PMID- 19088770
TI  - Short-term high-intensity interval training improves phosphocreatine recovery
      kinetics following moderate-intensity exercise in humans.
AB  - Previous studies have shown that high-intensity training improves biochemical
      markers of oxidative potential in skeletal muscle within a 2-week period. The
      purpose of this study was to examine the effect of short-term high-intensity
      interval training on the time constant () of phosphocreatine (PCr) recovery
      following moderate-intensity exercise, an in vivo measure of functional oxidative
      capacity. Seven healthy active subjects (age, 21 +/- 4 years; body mass, 69 +/-
      11 kg) performed 6 sessions of 4-6 maximal-effort 30 s cycling intervals within a
      2-week period, and 7 subjects (age, 24 +/- 5 years; body mass, 80 +/- 15 kg)
      served as controls. Prior to and following training, phosphorous-31 magnetic
      resonance spectroscopy (31P-MRS; GE 3T Excite System) was used to measure
      relative changes in high-energy phosphates and intracellular pH of the quadriceps
      muscles during gated dynamic leg-extension exercise (3 cycles of 90 s exercise
      and 5 min of rest). A monoexponential model was used to estimate the of PCr
      recovery. The of PCr recovery after leg-extension exercise was reduced by 14%
      with high-intensity interval training (pretraining, 43 +/- 14 s vs. post
      training, 37 +/- 15 s; p < 0.05) with no change in the control group (44 +/- 12 s
      vs. 43 +/- 12 s, respectively; p > 0.05). These findings demonstrate that short
      term high-intensity interval training is an effective means of increasing
      functional oxidative capacity in skeletal muscle.

PMID- 19088771
TI  - Greater bilateral deficit in leg press than in handgrip exercise might be linked
      to differences in postural stability requirements.
AB  - Bilateral deficit is defined as the difference in the summed force between
      contracting muscles alone and contracting contralateral homologous muscles in
      combination. The purpose of the study was to investigate how postural stability
      influences bilateral deficit by comparing an exercise requiring more postural
      stability (the leg press) with an exercise requiring less postural stability (the
      handgrip). Eight participants volunteered for the study (3 males, 5 females).
      Maximal strength was determined by a 1-repetition maximum for the leg press
      (weight machine) and handgrip (dynamometer) exercises. Electromyography was used
      to measure activation of the effectors (flexor carpi ulnaris for the handgrip and
      vastus lateralis for the leg press) and the core muscles (rectus abdominis and
      external obliques). Bilateral deficit was greater in the leg press (-12.08 +/-
      10.22%) than the handgrip (-0.677 +/- 5.00%; p < 0.05). Muscle activation of the
      effectors and core muscles was not significantly different between unilateral and
      bilateral conditions for either exercise. However, core muscle activation was
      significantly greater during the leg press (48.30 +/- 19.60 microV) than during
      the handgrip (16.50 +/- 8.10 microV; p < 0.05) exercise. These results support
      the hypothesis that an exercise requiring more postural stability (e.g., the leg
      press) will have a larger deficit and greater activation of core muscles than an
      exercise requiring less postural stability (e.g., the handgrip). Since the
      bilateral deficit was only apparent for the leg press exercise, we conclude that
      postural stability requirements might influence the magnitude of bilateral
      deficit.

PMID- 19088772
TI  - Effects of xanthine oxidase inhibition on oxidative stress and swimming
      performance in rats.
AB  - The aim of this study was to examine the effect of allopurinol, a xanthine
      oxidase inhibitor, on oxidative stress and physical performance after swimming
      until exhaustion in rats. Blood and gastrocnemius muscle samples were collected
      before, immediately after, and 5 h after exercise and the respective timepoints
      after allopurinol administration. Xanthine oxidase and total antioxidant capacity
      (TAC) were determined in plasma and muscle, whereas catalase activity and reduced
      (GSH) and oxidized (GSSG) glutathione were measured in erythrocytes and muscle.
      Thiobarbituric acid-reactive substances (TBARS) and protein carbonyls (PC) were
      determined in plasma, erythrocytes, and muscle. As expected, allopurinol
      inhibited xanthine oxidase activity. Compared with their nonallopurinol-treated
      counterparts, rats treated with allopurinol showed a 35% decrease in physical
      performance, as indicated by the shorter swimming time to exhaustion. Exercise
      alone increased PC and TBARS concentration in plasma, erythrocytes, and
      gastrocnemius muscle. Similarly, allopurinol alone increased PC and TBARS
      concentration in erythrocytes and gastrocnemius muscle, decreased TAC in plasma
      and gastrocnemius muscle, and decreased the GSH:GSSG ratio in erythrocytes. Our
      data illustrate that, in general, exercise and allopurinol alone increased the
      levels of most of the oxidative stress markers measured in plasma, erythrocytes,
      and gastrocnemius muscle. Xanthine oxidase inhibition provoked a marked reduction
      in physical performance.

PMID- 19088773
TI  - Validation of the Kenz Lifecorder EX and ActiGraph GT1M accelerometers for
      walking and running in adults.
AB  - Accelerometer-based activity monitors are commonly used by researchers and
      clinicians to assess physical activity. Recently, the Kenz Lifecorder EX (KL) and
      ActiGraph GT1M (AG) accelerometers have been made commercially available, but
      there is limited research on the validity of these devices. Therefore, we sought
      to validate step count, activity energy expenditure (EE), and total EE output
      from the KL and AG during treadmill walking and running. Ten male and 10 female
      participants performed 10 min treadmill walking and running trials, at speeds of
      54, 80, 107, 134, 161, and 188 m.min-1. Step counts were hand tallied by 2
      observers, and indirect calorimetry was used to validate the accelerometers'
      estimates of EE. AG total EE was calculated using the Freedson equation. Analysis
      of variance (ANOVA) and Pearson's correlations were used to analyze the data. At
      the slowest walking speed, the AG and KL counted 64% +/- 15% and 92% +/- 6% of
      the observed steps, respectively. At all other treadmill speeds, both activity
      monitors undercounted, compared with observed steps, by < or =3%. The KL
      underestimated activity EE at faster running speeds (p < 0.01), overestimated
      total EE at some walking speeds, and underestimated total EE at some running
      speeds (p < 0.01). The Freedson equation inaccurately measured total EE at most
      walking and running speeds. The KL and the AG are moderately priced
      accelerometers that provide researchers and clinicians with accurate estimates of
      step counts and activity EE at most walking and running speeds.

PMID- 19088774
TI  - Sport-specific assessment of lactate threshold and aerobic capacity throughout a
      collegiate hockey season.
AB  - The purpose of this study was to examine lactate threshold (LT) and maximal
      aerobic capacity with a sport-specific skating protocol throughout a competitive
      season in collegiate hockey players. We hypothesized that maximal aerobic
      capacity and skating velocity at LT would increase as the season progressed.
      Sixteen Division I college hockey players performed a graded exercise skating
      protocol to fatigue at 3 different times (pre-, mid-, and postseason). Subjects
      skated for 80 s during each stage, followed by 40 s of rest to allow for blood
      lactate sampling. Velocity at LT was similar during preseason (4.44 +/- 0.08 m.s
      1) and postseason (4.52 +/- 0.05 m.s-1) testing, but was significantly elevated
      at midseason (4.70 +/- 0.08 m.s-1; p < 0.01), compared with preseason. In
      contrast, LT as a percentage of maximal heart rate (HRmax) was unchanged
      throughout the season. HRmax remained constant throughout the season, at
      approximately 190 beats.min-1. Preseason maximal aerobic capacity (48.7 +/- 0.8
      mL.kg-1.min-1) was significantly higher than that at postseason (45.0 +/- 1.1
      mL.kg-1.min-1; p < 0.01). In conclusion, skating velocity at LT improved from pre
      to midseason, but this adaptation was not maintained at postseason.
      Additionally, maximal aerobic capacity was reduced from pre- to postseason. These
      findings suggest a need for aerobic training throughout the college hockey
      season.

PMID- 19088775
TI  - Differences in left ventricular mass between overweight and normal-weight
      preadolescent children.
AB  - This study examined cardiac and arterial differences between overweight and
      normal-weight preadolescent children. Twenty children (10.2 +/- 0.4 years of age)
      classified as overweight, on the basis of age-appropriate body mass index (BMI)
      cutoffs, were compared with 43 normal-weight controls. Height, mass, and body
      surface area were measured. Relative body fat and lean body mass were estimated
      from skinfold thickness. Each child's weekly physical activity metabolic
      equivalent (PAME) was calculated using a standardized questionnaire, and his or
      her sexual maturation was self-assessed using the Tanner scale. Peak aerobic
      power was assessed using a cycle ergometer and normalized to lean body mass. Mean
      arterial pressure was calculated from systolic and diastolic blood pressure (DBP)
      measurements taken with a Finapres. Cardiac dimensions were measured, using Mu
      mode 2-dimensional echocardiography, and normalized to body surface area and
      height2.7. Left carotid artery pulse pressure (CaPP) was assessed with
      applanation tomometry. Overweight boys and girls had a higher left ventricular
      mass (LVM) and LVMHT2.7 than normal-weight boys and girls. CaPP was signficantly
      lower in the overweight than in the normal-weight groups, whereas PAME and
      relative peak aerobic power were significantly higher in the boys than the girls.
      Although overweight children had significantly higher stroke volumes and cardiac
      outputs than normal-weight children, ejection fraction was similar in the weight
      groups. Adjusted LVMHT2.7 was associated with cardiac volume measurements, BMI,
      and DBP in normal-weight children, whereas in the overweight children LVMHT2.7
      did not significantly correlate with any variable. In conclusion, we found that
      cardiovascular adaptations can be seen in prepubescent overweight children as
      young as 10 years of age.

PMID- 19088776
TI  - Adaptive stretch-shortening contractions: diminished regenerative capacity with
      aging.
AB  - This study determined the age-related changes in acute events responsible for
      initiating skeletal muscle remodeling and (or) regeneration in the tibialis
      anterior muscle following a bout of stretch-shortening contractions (SSCs).
      Changes in muscle performance and morphology were quantified in young and old
      rats, following an acute exposure to adaptive SSCs at 6, 24, 48, 72, and 120 h
      postexposure (n = 6 for each age at each recovery period). Following SSC
      exposure, all performance measures were decreased in old rats throughout the 120
      h acute phase. Estimates of edema were increased in the old vs. young exposed
      muscle at 120 h recovery. Both young and old rats displayed an increase in
      developmental myosin heavy chain (MHCdev+) labeling in the exposed muscle,
      indicating muscle regeneration. However, old rats displayed diminished MHCdev+
      labeling, compared with young rats, suggesting limited remodeling and (or)
      regenerative capacity. Based on these data, diminished local muscle remodeling
      and (or) regeneration with aging may limit skeletal muscle adaptation following
      mechanical loading.

PMID- 19088777
TI  - Effects of aerobic training on the exercise-induced decline in short-passing
      ability in junior soccer players.
AB  - To examine the effects of aerobic interval training on the decline in short
      passing ability caused by a short bout of high-intensity intermittent activities.
      For this randomized controlled trial, 26 junior soccer players (mean age, 17.8 +/
      0.6 years; mean height, 178 +/- 5 cm; mean body mass, 74.5 +/- 6.9 kg) were
      recruited. After baseline measurements, subjects were randomly allocated to 1 of
      2 groups: the control group (CG) or the aerobic interval training group (ITG).
      The ITG completed 4 weeks of high-intensity aerobic training, consisting of 4
      bouts of running for 4 min at 90%-95% of maximal heart rate, with 3 min of active
      recovery between sets, in addition to normal training. Maximum oxygen uptake, Yo
      Yo Intermittent Recovery Test level 1 (YYIRT), and short-passing ability
      (measured using the Loughborough Soccer Passing Test (LSPT)) were measured before
      and after a 5 min high-intensity simulation (HIS), reproducing the most intense
      phase of a match. The ITG (n = 11), but not the CG (n = 10), showed a significant
      12% and 4% increase in YYIRT and maximal oxygen consumption after training,
      respectively, and reduced the worsening in LSPT penalty time after the HIS (p <
      0.05). The relative exercise intensity during HIS decreased in the ITG only (p <
      0.01). Our results demonstrated that junior soccer players may benefit from
      aerobic training to attenuate the decline in short-passing ability caused by a
      short bout of intermittent activities completed at the same pretraining workload.

PMID- 19088778
TI  - Between-day variability of net and gross oxygen uptake during graded treadmill
      walking: effects of different walking intensities on the reliability of
      locomotion economy.
AB  - There have been few studies of clinical relevance conducted on the reliability of
      walking economy. This study was designed to determine if walking economy
      reproducibility increases as a function of walking intensity, and if there is any
      advantage in expressing walking economy as net oxygen uptake (VO2) rather than
      gross VO2 for reproducibility purposes. Sixteen participants (9 males, 7 females;
      mean age, 22.3 +/- 4.3 years) performed resting, submaximal, and maximal
      protocols on 2 different days, under identical circumstances, within a 7 day
      period. The submaximal protocol consisted of five 5 min walks (4 km.h-1) at
      treadmill grades of 0%, 2.5%, 5.0%, 7.5%, and 10%. Findings indicate that
      increments of 2.5% in treadmill grade effectively increased gross and net VO2
      during walks. The reliability of net and gross measures increased as a function
      of walking relative intensity, reporting intraclass correlation coefficients
      ranging from 0.89-0.94 and 0.87-0.91, respectively, and mean coefficients of
      variation (CV) from 7.3%-3.6% and 8.8%-4.4%, respectively. There were no
      significant differences between the CV for gross and for net VO2 across the
      spectrum of walking relative intensities. In conclusion, there is no advantage of
      expressing walking economy as net VO2 instead of gross VO2 for reproducibility
      purposes, and a single treadmill testing session at a constant speed of 4 km.h-1
      is reliable for estimating group and individual walking economy, particularly at
      higher percent grades.

PMID- 19088779
TI  - Progesterone and estrogen influence postexercise leukocyte infiltration in
      overiectomized female rats.
AB  - Limited research has been conducted on the effects of progesterone alone, or in
      combination with estrogen, on leukocyte infiltration in skeletal muscle following
      exercise. To investigate the effects of these female sex hormones, ovariectomized
      female rats were divided into 4 exercise and 4 control groups: sham, estrogen,
      progesterone, and a combination of estrogen plus progesterone. Following 8 days
      of hormone replacement and 24 h postexercise, soleus (red) and superficial
      (white) vastus muscles were removed and immunostained for His48 (neutrophil)- and
      ED1 (macrophage)-positive cells. The postexercise increase in leukocyte
      infiltration was completely (p < 0.05) attenuated with estrogen supplementation
      alone in both muscle types, relative to sham. Progesterone treatment alone also
      resulted in a smaller (20%-30%) but significant (p < 0.05) attenuation of
      postexercise muscle leukocyte infiltration. The combination of estrogen and
      progesterone treatment did not significantly alter the attenuation seen with
      estrogen supplementation alone. Hence, progesterone can independently attenuate
      postexercise muscle leukocyte infiltration, albeit to a lesser degree than
      estrogen, and it will not negate or accentuate the effect of estrogen.

PMID- 19088780
TI  - Improved estimation of energy expenditure by artificial neural network modeling.
AB  - Estimation of energy expenditure in daily living conditions can be a tool for
      clinical assessment of health status, as well as a self-measure of lifestyle and
      general activity levels. Criterion measures are either prohibitively expensive or
      restricted to laboratory settings. Portable devices (heart rate monitors,
      pedometers) have gained recent popularity, but accuracy of the prediction
      equations remains questionable. This study applied an artificial neural network
      modeling approach to the problem of estimating energy expenditure with different
      dynamic inputs (accelerometry, heart rate above resting (HRar), and
      electromyography (EMG)). Nine feed-forward back-propagation models were trained,
      with the goal of minimizing the mean squared error (MSE) of the training
      datasets. Model 1 (accelerometry only) and model 2 (HRar only) performed poorly
      and had significantly greater MSE than all other models (p < 0.001). Model 3
      (combined accelerometry and HRar) had overall performance similar to EMG models.
      Validation of all models was performed by simulating untrained datasets. MSE of
      all models increased when tested with validation data. While models 1 and 2 again
      performed poorly, model 3 MSE was lower than all but 2 EMG models. Squared
      correlation coefficients of measured and predicted energy expenditure for models
      3 to 9 ranged from 0.745 to 0.817. Analysis of mean error within specific
      movement categories indicates that EMG models may be better at predicting higher
      intensity energy expenditure, but combined accelerometry and HRar provides an
      economical solution, with sufficient accuracy.

PMID- 19088781
TI  - Structural alterations of erythrocyte membrane components induced by exhaustive
      exercise.
AB  - Physical exercise was used as a model of the physiological modulator of free
      radical production to examine the effects of exercise-induced oxidative
      modifications on the physico-biochemical properties of erythrocyte membrane. The
      aim of our work was to investigate conformational changes of erythrocyte membrane
      proteins, membrane fluidity, and membrane susceptibility to disintegration.
      Venous blood was taken before, immediately after, and 1 h after an exhaustive
      incremental cycling test (30 W.min-1 ramp), performed by 11 healthy untrained
      males on balanced diets (mean age, 22 +/- 2 years; mean body mass index, 25 +/-
      4.5 kg.m-2). In response to this exercise, individual maximum heart rate was 195
      +/- 12 beats.min-1 and maximum wattage was 292 +/- 27 W. Electron paramagnetic
      resonance spectroscopy was used to investigate alterations in membrane proteins
      and membrane dynamics, and to measure production of radical species. The reducing
      potential of plasma (RPP) was measured using the reduction of 1,1-diphenyl-2
      picrylhydrazyl (DPPH) and the ferric-reducing ability of plasma. Exercise induced
      decreases in erythrocyte membrane fluidity in the polar region (p < 0.0001) and
      alterations in the conformational state of membrane proteins (p < 0.05). An
      increase in RPP was observed immediately after exercise (p < 0.001), with a
      further increase 1 h postexercise (p < 0.0001). Supporting measurements of lipid
      peroxidation showed an increase in thiobarbituric acid reactive substances
      immediately after exercise (p < 0.05) and at 1 h of recovery (p < 0.001);
      however, free radicals were not detected. Results indicate the existence of early
      postexercise mild oxidative stress after single-exercise performance, which
      induced structural changes in erythrocyte membrane components (protein
      aggregation) and in the membrane organization (lipids rigidization) that followed
      lipid peroxidation but did not lead to cellular hemolysis.

PMID- 19088782
TI  - Precision and reliability of strength (Jamar vs. Biodex handgrip) and body
      composition (dual-energy X-ray absorptiometry vs. bioimpedance analysis)
      measurements in advanced cancer patients.
AB  - Important deteriorations in body composition and strength occur and need to be
      accurately measured in advanced cancer patients (ACPs). The aim of this study was
      to establish the relationship between a single-frequency bioimpedance analyzer
      (BIA) and the dual-energy X-ray absorptiometer (DXA), as well as the Jamar
      handgrip dynometer and the Biodex handgrip attachment, and to determine the
      precision of each of these instruments in ACPs. Eighty-one ACPs with non-small
      cell lung cancer and gastrointestinal cancer were recruited from the McGill
      University Health Centre (Montreal, Que.). Consecutive paired measurements, with
      repositioning between measurements, were obtained for total-body DXA, BIA, Biodex
      handgrip, and BIA plus Jamar handgrip. The total-body percent coefficient of
      variation (%CV) for the BIA and DXA were 1.34 and 1.56 for fat mass (FM),
      respectively, and 0.42 and 0.72 for fat free mass (FFM), respectively. The %CV
      for the Jamar and Biodex handgrips were 6.3 and 16.7, respectively. Bland-Altman
      plots were used to characterize the limits of agreement between DXA and BIA for
      FM (4.60 +/- 7.80 (-3.19 to 12.39) kg) and FFM (-1.87 +/- 7.16 (-9.03 to 5.29)
      kg). Both DXA and BIA demonstrate good short-term precision in ACPs. However,
      given its poor accuracy, it remains to be determined if BIA can be used to
      monitor ACPs for changes in total-body tissue composition as a function of time,
      whether for observation or response to treatment. Furthermore, because of wide
      limits of agreement, the DXA and BIA cannot be used interchangeably in research
      or clinical settings. The Jamar handgrip dynamometer shows more consistency than
      the Biodex handgrip attachment in ACPs, and should therefore be the preferred
      measure of changes in strength over time.

PMID- 19088783
TI  - Skeletal muscle capillarization and oxidative metabolism in healthy smokers.
AB  - We investigated whether the lower fatigue resistance in smokers than in
      nonsmokers is caused by a compromised muscle oxidative metabolism. Using
      calibrated histochemistry, we found no differences in succinate dehydrogenase
      (SDH) activity, myoglobin concentration, or capillarization in sections of the
      vastus lateralis muscle between smokers and nonsmokers. The relationship between
      fatigue resistance and SDH activity in nonsmokers (r = 0.93; p = 0.02) is absent
      in smokers. This indicates that the lower muscle fatigue resistance of smokers
      can likely be attributed to causes other than differences in oxidative metabolism
      and capillarization.

PMID- 19088784
TI  - Time course alterations of plasma obestatin and growth hormone levels in response
      to short-term anaerobic exercise training in college women.
AB  - Obestatin is a 23-amino-acid peptide encoded by the same gene as ghrelin. Because
      there is a paucity of data concerning the effects of exercise on obestatin, this
      study investigated the effect of anaerobic exercise training-detraining on
      obestatin and growth hormone (GH) plasma levels. Ten young female volunteers
      participated. Blood was collected 24 h before, and 24 h, 48 h and 7 days after
      the training. The data indicate that anaerobic training caused a significant
      reduction in GH levels but had no effect on plasma obestatin concentrations.

PMID- 19088785
TI  - Following 2 diet-restricted male outdoor rock climbers: impact on oxidative
      stress and improvements in markers of cardiovascular risk.
AB  - Lower body fat percentage is positively associated with climbing performance.
      This may lead climbers to practice unhealthy diet restriction when no sport
      specific nutrition information exists. This study examined whether prolonged diet
      restriction affects body composition, oxidative stress, or other potential health
      risks in outdoor rock climbers. Two healthy male climbers conducted a 5 week rock
      climbing trip with a limited food budget ($1 each per day). Subjects underwent an
      energy restriction of approximately 40%. Loss of body weight and fat mass at week
      5 were 5.8% and 16.1%, respectively, and were accompanied by significant
      subcutaneous fat loss in the iliac crest and abdomen. Triacylglycerols (TG), free
      fatty acids and C-reactive protein (CRP) dramatically decreased from baseline to
      week 2, and then maintained the lower level until week 5. Plasma vitamin C was
      below the normal range, and F2-isoprostanes, a marker of oxidative stress,
      continuously increased to week 5. Superoxide dismutase and glutathione peroxidase
      increased to week 2, but had returned to baseline levels at week 5. These results
      indicate that prolonged reduced energy intake while climbing may have an impact
      on weight loss and fat mass loss, which may contribute to low circulating TG and
      CRP, indicating improvements in markers of cardiovascular risk, and may lead to
      increased oxidative stress and reduced circulating antioxidants. Further studies
      are warranted to determine whether antioxidant supplementation or increased
      energy intake reduce oxidative stress.

PMID- 19088789
TI  - Coffee consumption and risk of type 2 diabetes, cardiovascular diseases, and
      cancer.
AB  - Numerous epidemiological studies have evaluated the association between coffee
      consumption and risk of type 2 diabetes, coronary heart disease, and various
      cancers. This paper briefly reviews the evidence for a relation between coffee
      consumption and these conditions, with particular attention to methodological
      issues. Several early studies suggested that coffee consumption could result in a
      marked increase in risk of coronary heart disease and several types of cancer.
      However, more recent prospective cohort studies that are less prone to selection
      and information bias have not confirmed these findings. High consumption of
      unfiltered types of coffee, such as French press and boiled coffee, has been
      shown to increase low-density-lipoprotein-cholesterol concentrations. In
      addition, limiting caffeinated coffee intake during pregnancy seems a prudent
      choice. However, evidence has been accumulating that frequent consumption of
      coffee may reduce risk of type 2 diabetes and liver cancer. Further experimental
      studies are warranted to elucidate the underlying mechanisms and possibly
      identify the components in coffee that are responsible for these putative
      effects. In sum, the currently available evidence on coffee and risk of
      cardiovascular diseases and cancer is largely reassuring, and suggests that, for
      the general population, addressing other health-related behaviors has priority
      for the prevention of chronic diseases.

PMID- 19088790
TI  - Effect of caffeine on the neuromuscular system--potential as an ergogenic aid.
AB  - The ergogenic effect of caffeine on endurance exercise performance is
      multifactorial; however, there is evidence for an effect on both the central
      nervous system and the excitation-contraction coupling of skeletal muscle. The
      increase in exercise performance seen following intracerebroventrical caffeine
      injection in rats provides strong evidence for a central ergogenic effect. The
      central ergogenic effect is not likely related to the ability of caffeine to
      promote wakefulness, but could be due to an increase in the pain and effort
      perception threshold. There is no evidence that caffeine alters peripheral nerve
      conduction velocity or neuromuscular transmission, and 1 study showed that motor
      unit synchronization was not altered by caffeine. Studies have also shown that
      caffeine can have a direct effect on skeletal muscle that could be ergogenic. For
      example, patients with high cervical spinal cord lesions showed improvements in
      stimulated contractile force during cycling, in spite of the fact that they have
      no peripheral pain input and no sympathetic nervous system response. Two studies
      have found a potentiation of force production during submaximal stimulation
      intensities, and 1 found that the M-wave amplitude was not altered by caffeine.
      Together, these studies suggest that caffeine can enhance contractile force
      during submaximal contractions by potentiating calcium release from the ryanodine
      receptor, not by altering sarcoplasmic excitability. Furthermore, the
      potentiation of force during submaximal electrical stimulation is identical in
      habitual and nonhabitual caffeine consumers. In summary, the ergogenic effects of
      caffeine during endurance activity are mediated partly by enhanced contractile
      force and partly by a reduction in perceived exertion, possibly though a blunting
      of effort and (or) pain.

PMID- 19088791
TI  - Coffee, glucose homeostasis, and insulin resistance: physiological mechanisms and
      mediators.
AB  - Epidemiological studies show coffee consumption to be correlated to large risk
      reductions in the prevalence of type 2 diabetes (T2D). Such correlations are seen
      with decaffeinated and caffeinated coffee, and occur regardless of gender, method
      of brewing, or geography. They also exist despite clear evidence showing that
      caffeine causes acute postprandial hyperglycemia and lower whole-body insulin
      sensitivity. As the beneficial effects of coffee consumption exist for both
      decaffeinated and caffeinated coffee, a component of coffee other than caffeine
      must be responsible. This review examines the specific coffee compounds
      responsible for coffee's effects on T2D, and their potential physiological
      mechanisms of action. Being plant-derived, coffee contains many beneficial
      compounds found in fruits and vegetables, including antioxidants. In fact, coffee
      is the largest source of dietary antioxidants in industrialized nations. When
      green coffee is roasted at high temperatures, Maillard reactions create a number
      of unique compounds. Roasting causes a portion of the antioxidant, chlorogenic
      acid, to be transformed into quinides, compounds known to alter blood glucose
      levels. Coffee consumption may also mediate levels of gut peptides (glucose
      dependent insulinotropic polypeptide and glucagon-like peptide-1), hormones
      intimately involved in the regulation of satiety and insulin secretion. Finally,
      coffee may have prebiotic-like properties, altering gut flora and ultimately
      digestion. In summary, it is evident that a better understanding of the role of
      coffee in the development and prevention of T2D has the potential to uncover
      novel therapeutic targets and nutraceutical formulations for the disease.

PMID- 19088792
TI  - Consumption of dietary caffeine and coffee in physically active populations:
      physiological interactions.
AB  - Caffeine is a proven ergogenic aid, increasing athletic performance, endurance,
      and mental chronometry at doses as low as 1-3 mg.kg-1. As coffee is a readily
      available and commonly ingested form of caffeine, the two are often equated.
      However, coffee also contains hundreds of other biologically active compounds,
      many of which are metabolically distinct from caffeine. The purpose of this
      review was to examine the prevalence of coffee and (or) caffeine consumption
      among elite Canadian athletes, and to delineate the effects of coffee and
      caffeine on physical activity, weight maintenance, performance, and metabolism. A
      total of 270 self-reported 3-day food records were examined for caffeine intake
      from athletes registered with Canadian Sport Centres in 2005 and 2006. Athletes
      ranged in age from 16-45 years, and competed in 38 different sports. Results
      showed that 30% of athletes ingested >1 mg.kg-1.day-1 from a variety of sources.
      Average daily intake was 0.85 +/- 13 mg.kg-1. Caffeine intake was not correlated
      with any 1 sport; the 10 highest caffeine users were athletes from 9 different
      sports, including skill, endurance, and power sports. No differences were noted
      for average caffeine ingestion between summer and winter sports. High caffeine
      intakes corresponded to coffee ingestion, with the 25 highest individual intakes
      (193-895 mg.day-1) from coffee drinkers. In summary, it can be concluded that the
      majority of high-level Canadian athletes consume dietary caffeine primarily in
      the form of coffee. However, levels consumed are insufficient to elicit
      performance enhancement. Potential detrimental effects of caffeine consumption on
      exercise performance include gastric upset, withdrawal, sleep disturbance, and
      interactions with other dietary supplements.

PMID- 19088793
TI  - Does caffeine alter muscle carbohydrate and fat metabolism during exercise?
AB  - Caffeine, an adenosine receptor antagonist, has been studied for decades as a
      putative ergogenic aid. In the past 2 decades, the information has overwhelmingly
      demonstrated that it indeed is a powerful ergogenic aid, and frequently theories
      have been proposed that this is due to alterations in fat and carbohydrate
      metabolism. While caffeine certainly mobilizes fatty acids from adipose tissue,
      rarely have measures of the respiratory exchange ratio indicated an increase in
      fat oxidation. However, this is a difficult measure to perform accurately during
      exercise, and small changes could be physiologically important. The few studies
      examining human muscle metabolism directly have also supported the fact that
      there is no change in fat or carbohydrate metabolism, but these usually have had
      a small sample size. We combined the data from muscle biopsy analyses of several
      similar studies to generate a sample size of 16-44, depending on the measure. We
      examined muscle glycogen, citrate, acetyl-CoA, glucose-6-phosphate, and cyclic
      adenosine monophosphate (cAMP) in resting samples and in those obtained after 10
      15 min of exercise at 70%-85% maximal oxygen consumption. Exercise decreased (p <
      0.05) glycogen and increased (p < 0.05) citrate, acetyl-CoA, and glucose-6
      phosphate. The only effects of caffeine were to increase (p < 0.05) citrate in
      resting muscle and cAMP in exercise. There is very little evidence to support the
      hypothesis that caffeine has ergogenic effects as a result of enhanced fat
      oxidation. Individuals may, however, respond differently to the effects of
      caffeine, and there is growing evidence that this could be explained by common
      genetic variations.

PMID- 19088794
TI  - Caffeine and sports performance.
AB  - Athletes are among the groups of people who are interested in the effects of
      caffeine on endurance and exercise capacity. Although many studies have
      investigated the effect of caffeine ingestion on exercise, not all are suited to
      draw conclusions regarding caffeine and sports performance. Characteristics of
      studies that can better explore the issues of athletes include the use of well
      trained subjects, conditions that reflect actual practices in sport, and exercise
      protocols that simulate real-life events. There is a scarcity of field-based
      studies and investigations involving elite performers. Researchers are encouraged
      to use statistical analyses that consider the magnitude of changes, and to
      establish whether these are meaningful to the outcome of sport. The available
      literature that follows such guidelines suggests that performance benefits can be
      seen with moderate amounts (~3 mg.kg-1 body mass) of caffeine. Furthermore, these
      benefits are likely to occur across a range of sports, including endurance
      events, stop-and-go events (e.g., team and racquet sports), and sports involving
      sustained high-intensity activity lasting from 1-60 min (e.g., swimming, rowing,
      and middle and distance running races). The direct effects on single events
      involving strength and power, such as lifts, throws, and sprints, are unclear.
      Further studies are needed to better elucidate the range of protocols (timing and
      amount of doses) that produce benefits and the range of sports to which these may
      apply. Individual responses, the politics of sport, and the effects of caffeine
      on other goals, such as sleep, hydration, and refuelling, also need to be
      considered.

PMID- 19088795
TI  - Encapsulation of glutamine synthetase in mouse erythrocytes: a new procedure for
      ammonia detoxification.
AB  - There are a number of pathological situations in which ammonia levels increase
      leading to hyperammonemia, which may cause neurological alterations and can lead
      to coma and death. Currently, there are no efficient treatments allowing rapid
      and sustained decrease of ammonia levels in these situations. A way to increase
      ammonia detoxification would be to increase its incorporation in glutamine by
      glutamine synthetase. The aim of this work was to develop a procedure to
      encapsulate glutamine synthetase in mouse erythrocytes and to assess whether
      administration of these erythrocytes containing glutamine synthetase (GS) reduce
      ammonia levels in hyperammonemic mice. The procedure developed allowed the
      encapsulation of 3 +/- 0.25 IU of GS / mL of erythrocytes with a 70% cell
      recovery. Most metabolites, including ATP, remained unaltered in glutamine
      synthetase-loaded erythrocytes (named ammocytes by us) compared with native
      erythrocytes. The glutamine synthetase-loaded ammocytes injected in mice survived
      and retained essentially all of their glutamine synthetase activity for at least
      48 h in vivo. Injection of these ammocytes into hyperammonemic mice reduced
      ammonia levels in the blood by about 50%. The results reported indicate that
      ammocytes are able to keep their integrity, normal energy metabolism, the
      inserted glutamine synthetase activity, and can be useful to reduce ammonia
      levels in hyperammonemic situations.

PMID- 19088796
TI  - Effect of oxidative stress on the expression of t-PA, u-PA, u-PAR, and PAI-1 in
      endothelial cells.
AB  - In this study we examined the effects of exogenous nitric oxide (sodium
      nitroprusside, SNP) and hydrogen peroxide (H2O2) on the expression level of
      tissue-type plasminogen activator (t-PA), urokinase-type plasminogen activator (u
      PA), urokinase-type plasminogen activator receptor (u-PAR), and plasminogen
      activator inhibitor type 1 (PAI-1) in human umbilical vein endothelial cells
      (HUVEC). The expression of selected genes involved in fibrynolysis under the
      influence of oxidative stress was analyzed at the levels of mRNA, protein, and
      promoter activity. The results of the conducted studies revealed that oxidative
      stress in endothelial cells causes a significant increase in PAI-1 and u-PAR
      expression and a moderate increase in t-PA and u-PA expression at all of the
      investigated levels. We attempted to elucidate the molecular signaling mechanisms
      by which SNP and H2O2 regulate expression of the respective fibrinolytic factors.
      Therefore, we tested the protein levels of AP-1, NF-kappaB, and HIF-1 and their
      DNA-binding activity in endothelial cells subjected to oxidative stress. We found
      strong correlation between AP-1, NF-kappaB, and HIF-1 in the contribution of
      regulation of selected genes. In addition, we also found that the inhibition of
      PAI-1 synthesis by antisense oligonucleotide to PAI-1 mRNA results in markedly
      increased u-PAR expression and that NF-kappaB and AP-1 are involved in this
      regulation.

PMID- 19088797
TI  - Recombinant mouse SPARC promotes parietal endoderm differentiation and
      cardiomyogenesis in embryoid bodies.
AB  - In the absence of leukemia inhibitory factor, murine embryonic stem cells
      cultured in vitro spontaneously aggregate to from three-dimensional embryoid
      bodies that differentiate to produce hematopoietic, endothelial, muscle, and
      neuronal cell lineages in a manner recapitulating the events of early
      embryogenesis. Cardiomyogenesis in embryoid bodies was recently demonstrated to
      be promoted by PYS-2-derived native SPARC (secreted protein, acidic and rich in
      cysteine), whose expression is upregulated in parietal endoderm at the onset of
      the epithelial to mesenchymal transition. Here, we confirm the stimulatory
      effects of mouse SPARC on cardiomyogenesis using a recombinant baculovirus
      produced protein (rmSPARC). Embryoid bodies cultured in the presence of
      glycosylated rmSPARC, or an unglycosylated peptide spanning the C-terminal EF
      hand domain, developed greater numbers of beating cardiomyocytes than did time
      matched controls, with enhanced expression of cardiac marker genes including
      Nkx2.5, Troponin, BMP-2, and MHCalpha. Histochemical analysis revealed an
      expansion of the peripheral endoderm, with thicker layers of extracellular matrix
      (ECM) material observed atop underlying cells. Embryoid bodies treated with SPARC
      also displayed increased adherence to polystyrene culture dishes, with enhanced
      expression of ECM mRNAs including collagen IValpha3, collagen IValpha5, and
      laminin alpha1. These results indicate that, in addition to the promotion of
      cardiomyogenesis, SPARC may also help regulate the molecular composition and
      organization of ECM secreted by the mesenchymal parietal endoderm.

PMID- 19088798
TI  - Amyloid peptide inhibits ATP release from human erythrocytes.
AB  - The oxygen required to meet metabolic needs of all tissues is delivered by the
      erythrocyte, a small, flexible cell, which, in mammals, is devoid of a nucleus
      and mitochondria. Despite its simple appearance, this cell has an important role
      in its own distribution, enabling the delivery of oxygen to precisely meet
      localized metabolic need. When an erythrocyte enters in a hypoxic area, a
      signalling pathway is activated within the cell resulting in the release of ATP
      in amounts adequate to activate purinergic receptors on vascular endothelium,
      which trigger secretion of nitric oxide and other factors resulting in
      vasodilatation. Among other mechanisms, binding of deoxyhemoglobin to the
      cytoplasmic domain of the anion-exchange protein band 3 is probably involved in
      this pathway. The present study investigates the effect of amyloid beta peptide
      exposure on this molecular mechanism. We report that deoxygenated human
      erythrocytes fail to release ATP following 24 h exposure to amyloid beta peptide.
      Concurrently, amyloid beta peptide induces caspase 3 activation. Preincubation of
      amyloid beta peptide treated erythrocytes with a specific inhibitor of caspase 3
      prevents amyloid-induced caspase 3 activation and restores the erythrocyte's
      ability to release ATP under deoxygenated conditions. Since the activity of red
      cell phosphofructokinase, a key step in glycolytic flux, is not modified within
      the red cell following amyloid peptide exposure, it is likely that ATP release
      reduction is not dependent on glycolytic flux alterations. It has also been
      suggested that the heterotrimeric G protein, Gi, and adenylyl cyclase are
      downstream critical components of the pathway responsible for ATP release. We
      show that cAMP synthesis and ATP release are not failed in amyloid-peptide
      treated erythrocytes in response to incubation with mastoparan 7 or forskolin
      plus 3-isobutyl-1-methyl xanthine, agents that stimulate cAMP synthesis. In
      conclusion, these results indicate that amyloid beta peptide inhibits ATP release
      from deoxygenated erythrocytes by activating red cell caspase 3, suggesting a
      pathophysiologic role for vascular amyloid peptide in Alzheimer's disease.

PMID- 19088799
TI  - Involvement of myosin VI immunoanalog in pinocytosis and phagocytosis in Amoeba
      proteus.
AB  - Recently, we found a 130-kDa myosin VI immunoanalog in amoeba, which bound to
      actin in an ATP-sensitive manner and in migrating amoebae colocalized to
      filamentous actin and dynamin II-containing vesicular structures. To further
      characterize this protein, we assessed its involvement in amoeba pinocytosis and
      phagocytosis. Confocal immunofluorescence microscopy and electron microscopy of
      immunogold-stained cells revealed that, in pinocytotic and phagocytotic amoebae,
      the myosin VI immunoanalog was visible throughout the cells, including
      pinocytotic channels and pinocytotic vesicles as well as phagosomes and emerging
      phagocytic cups. Blocking endogenous protein with anti-porcine myosin VI antibody
      (introduced into cells by means of microinjection) caused severe defects in
      pinocytosis and phagocytosis. In comparison with control cells, the treated
      amoebae formed ~75% less pinocytotic channels and phagocytosed ~65% less
      Tetrahymena cells. These data indicate that the myosin VI immunoanalog has an
      important role in pinocytosis and phagocytosis in Amoeba proteus (Pal.).

PMID- 19088800
TI  - Thermotolerance induced at a fever temperature of 40 degrees C protects cells
      against hyperthermia-induced apoptosis mediated by death receptor signalling.
AB  - Mild temperatures such as 40 degrees C are physiological and occur during fevers.
      This study determines whether mild thermotolerance induced at 40 degrees C can
      protect HeLa cells against activation of the death receptor pathway of apoptosis
      by lethal hyperthermia (42-45 degrees C). Protein expression of heat shock
      proteins (Hsps) 27, 32, 60, 72, 90, and 110 was increased in thermotolerant cells
      (3 h, 40 degrees C). Lethal hyperthermia (42-43 degrees C) caused cell death by
      apoptosis, but at 45 degrees C there was a switch to necrosis. Mild
      thermotolerance protected cells against heat-induced apoptosis (Annexin V
      labelling). Hyperthermia induced apoptosis through generation of reactive oxygen
      species (ROS) and death receptor signalling. The antioxidant polyethylene glycol
      catalase abrogated increased expression of Fas death ligand and caspase-8
      activation in response to lethal hyperthermia (42-43 degrees C). Mild
      thermotolerance attenuated the heat induction of ROS and FasL, which were
      initiating events in death receptor activation and signalling. Mild
      thermotolerance inhibited early events in hyperthermia-induced death receptor
      apoptosis such as Fas-associated death domain (FADD) translocation to membranes,
      caspase-8 activation, and tBid translocation to mitochondria. Downstream events
      in apoptosis such as caspase-3 activation, cleavage of PARP and ICAD, and
      chromatin condensation were also diminished in thermotolerant cells. It is
      important to improve knowledge about adaptive responses induced by exposure to
      mild stresses, such as fever temperatures, which can protect cells against
      subsequent exposure to lethal stress.

PMID- 19088801
TI  - The influence of sterols on the conformation of recombinant mitochondrial porin
      in detergent.
AB  - Mitochondrial porins (voltage-dependent anion-selective channels, VDAC) are key
      contributors to cellular metabolism. When isolated from mitochondria porins
      copurify with sterols, and some isolated forms of the protein require sterol for
      insertion into artificial membranes. Nonetheless, the contributions of sterols to
      the folded state of mitochondrial porin are not understood. Recently, with the
      goal of high-resolution structural studies, several laboratories have developed
      methods for folding recombinant porins at high concentration in detergent. In the
      present study, recombinant Neurospora crassa porin solubilized in detergent
      sterol mixtures was examined. Sterols do not significantly alter the secondary
      structure of porin in lauryl dimethylamine oxide, nor in a mixture of sodium
      dodecylsulfate and dodecylmaltopyranoside. However, as detected by near-UV
      circular dichroism spectropolarimetry and fluorescence spectroscopy, the
      environments surrounding the aromatic amino acids in the detergent-sterol
      solubilized protein are measurably different from those in detergent alone.
      Furthermore, the effects are different in the presence of ergosterol, the native
      sterol in fungal mitochondria, and cholesterol. While these influences on the
      tertiary arrangement of detergent-solubilized porin are subtle, they may
      contribute to the generation of a form of the protein competent for insertion
      into the artificial bilayers used for electrophysiological analyses, and should
      be considered in future structural studies of porin.

PMID- 19088802
TI  - Beneficial effect of 3,4,5,6-tetrahydroxyxanthone on dyslipidemia in
      apolipoprotein E-deficient mice.
AB  - Previous investigations have shown that decreased expression of angiopoietin-like
      protein 3 (Angptl3) is protective against dyslipidemia in atherosclerosis. The
      present study was conducted to test the effect of 3,4,5,6-tetrahydroxyxanthone, a
      xanthone compound, on dyslipidemia in apolipoprotein E-deficient (ApoE-/-) mice.
      Forty mice were randomly divided into 4 groups (n = 10): control group (C57BL/6J
      mice), ApoE-/-mice group, and two groups of ApoE-/- mice treated with 3,4,5,6
      tetrahydroxyxanthone (10 or 30 mg/kg per day). Eight weeks after treatment, lipid
      levels in the blood and liver, expression of hepatic Angptl3, and adipose tissue
      lipoprotein lipase (LPL) were determined. Treatment with 3,4,5,6
      tetrahydroxyxanthone (10 or 30 mg/kg) significantly decreased plasma and hepatic
      total cholesterol and triglyceride concentrations, increased plasma high-density
      lipoprotein cholesterol, and significantly downregulated expression of Angptl3
      mRNA and protein concomitantly with upregulated expression of LPL mRNA. In
      addition, T0901317 (a liver X receptor ligand) caused elevated expression of
      hepatic Angptl3 mRNA and protein, and the effect of T0901317 was also abrogated
      by 3,4,5,6-tetrahydroxyxanthone in vivo and in vitro. The present results suggest
      that the beneficial effect of 3,4,5,6-tetrahydroxyxanthone on dyslipidemia may be
      related to reduced expression of Angptl3.

PMID- 19088803
TI  - Myocardial protection with enalaprilat in patients unresponsive to ischemic
      preconditioning during percutaneous coronary intervention.
AB  - Cardioprotection due to angiotensin enzyme inhibitors is attributed, at least in
      part, to the inhibition of bradykinin breakdown and the preconditioning effect of
      the elevated endogenous bradykinin level. We have previously shown that in
      patients undergoing percutaneous coronary intervention, one 120-second balloon
      inflation is insufficient to precondition the heart. The objective of the present
      study was to examine whether the administration of enalaprilat to these patients
      results in protection. Twenty patients underwent two 120-second coronary artery
      occlusions separated by a reperfusion interval of 10 min. Ten patients were given
      50 microg x min-1 enalaprilat in an intracoronary infusion between the balloon
      inflations, whereas the others received an infusion of saline. In the latter
      control patients, there were no significant differences in ST-segment elevation
      between the consecutive occlusions (peak ST: 1.61 +/- 0.17 vs. 1.61 +/- 0.16 mV;
      time to reach 0.5 mV ST elevation: 16 +/- 4 vs. 22 +/- 7 s; mean ST: 1.03 +/-
      0.12 vs. 1.02 +/- 0.11 mV). In the patients who received enalaprilat before the
      second balloon inflation, the ST-segment elevation was significantly less
      pronounced and slower during the second inflation than during the first (peak ST:
      1.80 +/- 0.18 vs. 1.41 +/- 0.19 mV; time to reach 0.5 mV ST elevation: 18 +/- 4
      vs. 30 +/- 4 s; mean ST: 1.04 +/- 0.11 vs. 0.85 +/- 0.14 mV). We conclude that
      enalaprilat administered during percutaneous coronary intervention provides
      protection to patients who do not have a protective response to the initial
      balloon inflation.

PMID- 19088804
TI  - Detrimental effects of nicotine on the acute gastric mucosal injury induced by
      ethanol: role of asymmetric dimethylarginine.
AB  - The aim of this study was to determine whether asymmetric dimethylarginine
      (ADMA), an endogenous inhibitor of nitric oxide synthase (NOS), is responsible
      for the detrimental effects of nicotine on ethanol-induced gastric mucosal injury
      and its underlying mechanisms. Gastric mucosal injury was induced by an injection
      of ethanol in the stomach in rats. Animals were pretreated with nicotine for 28
      days before ethanol injection. The gastric mucosal ulcer index (UI) and the
      levels of ADMA and NO in gastric juice were determined. In vitro, the cultured
      mucosal epithelial cells were treated with nicotine in the presence or absence of
      ethanol. The concentration of ADMA in the culture medium and the ratio of cell
      apoptosis were measured, and the effect of nicotine or ADMA alone on cell
      apoptosis was also examined. In rats treated with ethanol, the UI and ADMA levels
      were increased and the NO level was decreased, and these effects of ethanol were
      augmented by pretreatment with nicotine. Administration of nicotine alone did not
      show significant impact on UI, ADMA level, or NO level. In vitro, incubation of
      human epithelial cells with ethanol induced cell injury accompanied by increased
      ADMA levels in the culture medium, an effect which was amplified in the presence
      of nicotine. Similarly, ethanol was able to induce epithelial cell apoptosis that
      was exacerbated by nicotine. Incubation of epithelial cells with nicotine alone
      did not induce cell apoptosis, but administration of ADMA alone did induce cell
      apoptosis. The results suggest that the gastric mucosal injury induced by ethanol
      is augmented by nicotine, which is related to the increased ADMA level.

PMID- 19088805
TI  - Therapeutic effect and mechanism of proanthocyanidins from grape seeds in rats
      with TNBS-induced ulcerative colitis.
AB  - The aim of the study was to investigate the therapeutic effect and mechanism of
      proanthocyanidins from grape seeds (GSPE) in the treatment of ulcerative colitis
      (UC). Rats were intragastrically administered different doses of GSPE (100, 200,
      and 400 mg/kg) per day for 7 days after UC was twice-induced by intracolonic
      injection of 2,4,6-trinitrobenzene sulfonic acid (TNBS)dissolved in 50% ethanol.
      Sulfasalazine (SASP) at 200 mg/kg was used as a positive control drug.
      Macroscopic and microscopic damage scores and changes in weight/length ratio
      (mg/mm) of colon segments were analyzed. The levels of malonyldialdehyde (MDA),
      interleukin (IL)-1beta, IL-2, IL-4, and myeloperoxidase (MPO) activity in the
      colon tissues and MPO activity in the serum were all measured by biochemical
      methods or double antibody sandwich ELISA methods. Compared with the TNBS control
      group, GSPE treatment facilitated recovery of pathologic changes in the colon
      after insult with TNBS, as demonstrated by increased body weight (p < 0.01) and
      decreased colonic weight/length ratio (p < 0.01); GSPE also notably reduced the
      colonic macroscopic and microscopic damage scores (p < 0.01). The MPO activity in
      colon tissues and serum of rats treated with GSPE was significantly lower than
      that in the TNBS control group. The MDA and IL-1beta levels of colon tissues were
      also decreased in GSPE groups. The intestinal antiinflammatory effect of GSPE was
      accompanied by a significant improvement of IL-2 and IL-4 levels in the colon
      tissues of rats in the high-dose GSPE group (p < 0.05). Compared with the SASP
      group, GSPE groups had no significant difference in the therapeutic effect (p >
      0.05). GSPE exerts a beneficial antiinflammatory effect in the acute phase of
      TNBS-induced colitis in rats by downregulating some of the mediators involved in
      the intestinal inflammatory response, inhibiting inflammatory cell infiltration
      and antioxidation damage, promoting damaged tissue repair to improve colonic
      oxidative stress, decreasing production of proinflammatory cytokines IL-1beta,
      and increasing production of antiinflammatory cytokines IL-2 and IL-4.

PMID- 19088806
TI  - Diastolic calcium is elevated in metabolic recovery of cardiomyocytes expressing
      elevated levels of the Na+/H+ exchanger.
AB  - In the myocardium, the Na+/H+ exchanger isoform 1 (NHE1) plays a pivotal role in
      mediating ischemia-reperfusion (I/R) injury by causing intracellular Na+
      accumulation that results in a subsequent increase in intracellular calcium (Ca2+
      overload). One of the major clinical correlates of I/R injury is contractile
      dysfunction, in which Ca2+ overload via increased Na+/Ca2+ exchange is a major
      contributor. To better understand the cellular role of NHE1 during I/R injury,
      contractile function and calcium transients were measured during metabolic
      inhibition and recovery in single ventricular myocytes from transgenic mice with
      elevated NHE1 expression. During normoxic conditions, no differences were seen
      between NHE1-overexpressing cardiomyocytes and wild-type (WT) cardiomyocytes with
      respect to fractional cell shortening (FCS), rate of shortening (+dL/dt), and
      rate of relaxation (-dL/dt). When metabolic recovery followed metabolic
      inhibition, NHE1-overexpressing ventricular myocytes exhibited a significant
      increase in FCS (130.2% +/- 11.77% baseline) and +/-dL/dt (146.93% +/- 12.27%
      baseline). This correlated with a significant increase in the concentration of
      diastolic intracellular calcium, which was attenuated by the NHE1 inhibitor
      HOE694. These results indicate that in normoxic conditions, elevated NHE1
      expression does not alter contractile function. During metabolic recovery,
      however, elevated NHE1 expression increased diastolic Ca2+ loading that led to
      augmented cell contractility.

PMID- 19088807
TI  - Choline produces antiarrhythmic actions in animal models by cardiac M3 receptors:
      improvement of intracellular Ca2+ handling as a common mechanism.
AB  - It is well known that choline has protective effects on ischemic arrhythmias. We
      designed the present study to evaluate the antiarrhythmic effects of choline and
      to detect its related mechanisms in aconitine-induced rat and ouabain-induced
      guinea pig models of arrhythmia. Laser scanning confocal microscopy and patch
      clamp technique were utilized to study the action of choline on intracellular
      calcium concentration and L-type calcium current (ICa-L) of cardiac myocytes. M3
      receptor antagonist 4-DAMP (4-diphenylacetoxy-N-methylpiperidine-methiodide) was
      applied preliminarily to evaluate the role of the M3 receptor. Choline
      significantly increased the survival time of arrhythmic rats and guinea pigs,
      delayed the onset of arrhythmias and ventricular tachycardia, and decreased the
      arrhythmia score. The overload of intracellular Ca2+ induced by aconitine or
      ouabain was reduced in isolated myocytes pretreated with choline. Choline reduced
      the increased density of ICa-L induced by aconitine or ouabain. Moreover, the
      beneficial effects of choline were reversed by 4-DAMP. Choline produced
      antiarrhythmic actions on arrhythmia models by stimulating the cardiac M3
      receptor. The mechanism may be related to the improvement of Ca2+ handling.

PMID- 19088808
TI  - Energetics of Ca2+ homeostasis during ischemia-reperfusion on neonatal rat hearts
      under high-[K+] cardioplegia.
AB  - The mechanocalorimetric consequences and mechanisms involved in Ca2+ homeostasis
      during ischemia-reperfusion (I/R) as well as the protective role of cardioplegic
      pretreatment with high [K+] (25 mmol/L) and low or near-normal [Ca2+] (0.5 or 2
      mmol/L) were evaluated in a model of neonatal rat heart. Beating hearts from 10
      12-day-old rats were perfused with Krebs solution (2 mmol/L Ca2+) under both
      isotonic and isometric conditions. During pretreatment, hearts were exposed for
      20 min to either Krebs (control) or cardioplegia (CPG) before 15 min ischemia and
      45 min reperfusion while being continuously measured for either contractility or
      total heat rate (Ht) in a flow calorimeter. Contractile recovery after
      reperfusion in hearts exposed to ischemia only (control) was higher in the
      isometric hearts under optimal length (87.9% +/- 8.1%) than in the isotonic
      hearts (57.3% +/- 10.6%). This same behavior was found in hearts pretreated with
      CPG-0.5 mmol/L Ca2+. Ht in controls was reduced from 11.5 +/- 0.8 mW/g in the
      initial beating condition to 1.11 +/- 0.33 mW/g during ischemia and was increased
      to 13.02 +/- 0.93 mW/g (113.8% +/- 5.0% of preischemic) after reperfusion. Hearts
      pretreated with CPG-0.5 mmol/L Ca2+ showed the same behavior. However, when
      extracellular calcium ([Ca]o) was increased to 2 mmol/L under CPG, isotonic
      hearts, but not isometric hearts, significantly increased the contractile
      recovery to a maximum of 88.7% +/- 10.8% of preischemic levels. Ht was recovered
      to 92.1% +/- 4.3% of preischemic, suggesting that contractile recovery was less
      energetically expensive after CPG-2 mmol/L Ca2+ than it was in postischemic
      hearts exposed to control or CPG-0.5 mmol/L Ca2+. The role of the sarcoplasmic
      reticulum store was evaluated by pretreating hearts with 10 mmol/L caffeine,
      which reduced contractile recovery only under isometric conditions or after
      increasing [Ca]o in CPG under isotonic conditions, suggesting that the
      contribution of the sarcoplasmic reticulum was dependent on the fibre length or
      the [Ca]o. The inhibition of the reverse mode of the sarcolemmal Na/Ca exchanger
      (NCX) and the mitochondrial Ca uniporter (CaU) by KB-R7943 (KBR) at 5 micromol/L
      in CPG-0.5 mmol/L Ca2+ improved contractile recovery of isotonic hearts, whereas
      it decreased Ht at the start of reperfusion, suggesting that mitochondria could
      uptake Ca2+ via the mitochondrial CaU. Neither the positive inotropism nor Ht
      were changed by inhibiting the mitochondrial NCX with 10 micromol/L clonazepam in
      CPG-0.5 mmol/L Ca2+ + 5 micromol/L KBR, which suggests that the mitochondrial NCX
      does not have a role. Finally, the role of the forward mode of the sarcolemmal
      NCX was evidenced by the fall in contractile recovery with increased Ht when KBR
      was increased to 20 micromol/L and added to CPG-2 mmol/L Ca2+ + 10 mmol/L
      caffeine before I/R. Thus the sarcolemmal NCX was essential for removing the
      diastolic Ca2+ during the periods of CPG and I/R. In summary, Ca2+ homeostasis
      during I/R of neonatal rat hearts is different from that of adult rats. High-[K+]
      CPG protected neonatal hearts only under isotonic conditions, at a near-normal
      [Ca]o, or by exposure to KBR. Mitochondria were able to uptake Ca2+ via the
      mitochondrial CaU and reduce the Ca2+ available for contractile recovery.
      Nevertheless, after increasing [Ca]o in CPG, the sarcoplasmic reticulum had a
      main role in restoring contractility during reperfusion, as it does in adults.
      Thus, the degree of maturation of the heart must be taken into account to
      evaluate the effects of CPG and drugs on I/R.

PMID- 19088809
TI  - Meal-induced insulin sensitization and its parasympathetic regulation in humans.
AB  - In animal studies, the whole-body glucose disposal effect of insulin is low in
      the fasted state or after atropine infusion, but doubles after a meal, consistent
      with the hepatic insulin-sensitizing substance (HISS) hypothesis. We tested how a
      standardized test meal and atropine affected the dynamic response to insulin in
      humans. Insulin sensitivity was assessed in healthy male subjects (aged 28.9 +/-
      1.9 years, body mass index 23.3 +/- 0.8 kg.m-2) by using the rapid insulin
      sensitivity test (RIST), which is a transient euglycemic clamp. After a 24-hour
      fasting period, dynamic insulin sensitivity was assessed and then repeated 100
      min after the test meal. In a second protocol, the volunteers were fed the
      standardized test meal and intravenous atropine (0.5 mg) or saline (control
      group) was administered 50 min before insulin sensitivity assessment. Insulin
      sensitivity increased in the fed state (232.1% +/- 46.3%, n = 7) in comparison
      with the 24-hour fasted state. In the atropine protocol, the drug partially
      blocked (56.5% +/- 11.6%, n = 6) insulin sensitivity. In humans, feeding resulted
      in increased insulin sensitivity. The low dose of atropine in humans lead to a
      partial HISS-dependent decrease in insulin sensitivity. Meal-induced insulin
      sensitization occured in humans by a similar mechanism as that reported in other
      species. The sensitization process was regulated by a cholinergic 'feeding
      signal.'

PMID- 19088810
TI  - The Bo1-specific PCR marker AWW5L7 is predictive of boron tolerance status in a
      range of exotic durum and bread wheats.
AB  - High soil boron (B) constitutes a major soil problem in many parts of the world,
      particularly in low-rainfall areas and land under irrigation. Low accumulation of
      B in the shoot or grain of cereal crops is correlated with the maintenance of
      biomass production and grain yield under high B conditions, suggesting that this
      trait is an important component of field tolerance. A novel screening protocol to
      measure B accumulation in aerated and supported hydroponics was validated using a
      set of known and exotic bread wheat (Triticum aestivum L.) and durum wheat
      (Triticum turgidum L. subsp. durum (Desf.) Husn.) accessions. Furthermore, B
      accumulation in two Triticum urartu Tumanian ex Gandilyan and 54 Triticum
      monococcum L. accessions was measured and showed considerable phenotypic
      variation. However, B accumulation in these lines was higher than that observed
      in the most tolerant durum or bread wheats. Mapping of high B tolerance in the
      durum population AUS14010/Yallaroi revealed a locus possibly allelic to Bo1, a
      major source of B toxicity tolerance previously identified in bread wheat. Here,
      we show that the Bo1-specific codominant PCR marker AWW5L7 is predictive of B
      tolerance status among exotic durum and bread wheat accessions. All tolerant
      durum accessions assayed carried very similar AWW5L7 marker fragments, indicating
      wide distribution of this allele among tolerant durum wheats. Three bread wheat
      accessions had tolerance that was independent of Bo1 and is probably located on
      chromosome 4A. These lines represent a valuable genetic resource for B toxicity
      tolerance breeding in wheat.

PMID- 19088811
TI  - Cytotaxonomy of Simulium siamense Takaoka and Suzuki (Diptera: Simuliidae) in
      Thailand.
AB  - Larval polytene chromosomes of 1824 individuals of Simulium siamense Takaoka and
      Suzuki from 32 locations in northern, northeastern, eastern, and central Thailand
      were examined. Differences in sex chromosomes, fixed inversions, and the kind and
      frequency of floating inversions revealed five cytoforms (A, B, C, D, and E). In
      contrast to most Simulium species, females of S. siamense are the heterogametic
      sex (ZW) and males are the homogametic sex (ZZ). Cytoform A differs from the
      others by having 23 floating inversions and undifferentiated sex chromosomes (W0
      was undifferentiated from Z0). Cytoforms B, C, and D differ from each other by
      having different W chromosomes (W1, W2, and W3) in females. Cytoform E is
      characterized by having two fixed inversions, IS-1 and IIIS-2. Cytoform A is
      widely distributed throughout the geographic ranges of the species in northern,
      northeastern, eastern, and central Thailand, whereas cytoforms B, C, and D are
      restricted to a few locations in central Thailand. Although the larvae of the
      five cytoforms are morphologically similar, they seem to occupy different
      ecological habitats, which should be further investigated. At present, no
      definite conclusion can be drawn as to the taxonomic status of the cytoforms of
      S. siamense. However, this study indicates that S. siamense is represented by at
      least five cytoforms, of which cytoform B is the most distinct by having complete
      sex linkage and no floating inversions.

PMID- 19088812
TI  - The effect of transposon Pokey insertions on sequence variation in the 28S rRNA
      gene of Daphnia pulex.
AB  - The goal of this study was to determine the impact of breeding system and the
      presence of the transposon Pokey on intraindividual variation in 28S rRNA genes.
      We PCR-amplified, cloned, and sequenced 1000 nucleotides downstream of the Pokey
      insertion site in genes with and without insertions from 10 obligately and 10
      cyclically parthenogenetic isolates of Daphnia pulex. Variation among genes with
      Pokey insertions was higher than variation among genes without insertions in both
      cyclic and obligate isolates. Although the differences were not quite significant
      (p = 0.06 in both cases), the results suggest that Pokey insertions are likely to
      inhibit the homogenization of their host genes to some extent. We also observed
      that the complement of 28S rRNA alleles differed between genes with and without
      inserts in some isolates, suggesting that a particular inserted gene can persist
      for substantial periods of time and even spread within the rDNA array, despite
      the fact that insertions are deleterious. This apparently contradictory pattern
      can be explained if homogenization of rRNA genes occurs primarily by gene
      conversion, but copies with Pokey inserts can occasionally increase in frequency
      within arrays owing to unequal crossing over events that do not originate in the
      inserted genes themselves.

PMID- 19088813
TI  - Development and characterization of microsatellite markers for analysis of
      population differentiation in the tree legume Acacia koa (Fabaceae: Mimosoideae)
      in the Hawaiian Islands.
AB  - The aim of this research was to develop and use microsatellite markers to
      characterize the high-value timber tree Acacia koa (koa), which is endemic to the
      Hawaiian Islands. Genomic DNA fragments of 300-1000 bp were cloned and sequenced
      following enrichment for microsatellite motifs by PCR using 7 oligonucleotide
      repeat primers in separate reactions. Among 96 sequences analyzed, 63 contained
      unique microsatellite motifs flanked by variable sequences. A dual PCR method
      involving a primer walking step was used to develop 15 primer pairs. Another 16
      primer pairs were developed directly from the variable sequences on both sides of
      the microsatellite motifs. These 31 primer pairs were tested on 172 koa plants
      representing 11 populations collected from 4 of the major Hawaiian Islands. Nine
      of the primers that identified polymorphic microsatellite loci and 3 that
      detected unique alleles exclusively in some populations were used for genetic
      diversity studies of koa. Cluster analysis and multidimensional scaling of the
      allelic phenotype data revealed that koa from Kauai formed a distinct group
      separate from koa of the neighboring islands of Oahu, Maui, and Hawaii. The
      oldest of the four islands, Kauai, also had the most diverse populations of koa.

PMID- 19088814
TI  - Association mapping of yellow pigment in an elite collection of durum wheat
      cultivars and breeding lines.
AB  - Association mapping (AM) is an alternative or complementary strategy to QTL
      mapping for describing associations between genotype and phenotype based on
      linkage disequilibrium (LD). Yellow pigment (YP), an important end-use quality
      trait in durum wheat (Triticum turgidum L. var. durum), was evaluated to
      determine the ability of AM to identify previously published QTL and to identify
      genomic regions for further genetic dissection. The YP concentration was
      determined for 93 durum wheat accessions sampled from a variety of geographic
      origins. Analysis of population structure using distance- and model-based
      estimates indicated the presence of five subpopulations. Using subpopulation
      assignments as covariates, significant (P < 0.05) marker-trait associations for
      YP were detected on all chromosomes of the durum genome. Using AM, genomic
      regions housing known YP QTL were confirmed, most notably the group 7
      chromosomes. In addition, several markers on the group 1, 2, and 3 chromosomes
      were identified where QTL have yet to be reported. A phytoene synthase gene, Psy1
      B1, a potential candidate gene for YP, was significantly associated with YP and
      was in strong LD with microsatellite markers on the distal end of 7BL. Our
      results demonstrated that AM complemented traditional QTL mapping techniques and
      identified novel QTL that should be the target of further genetic dissection.

PMID- 19088815
TI  - A new gene for resistance to Dysaphis pyri in pear and identification of flanking
      microsatellite markers.
AB  - Dysaphis pyri is an important aphid pest of European pear (Pyrus communis)
      cultivars, none of which are currently reported to be resistant. In this study,
      we produced a progeny of the European pear Comice crossed with an accession of
      snow pear (Pyrus nivalis) that segregated for resistance to D. pyri in a
      Mendelian fashion, indicating the presence of a major gene, Dp-1. Following
      screening of the parents and seedlings with microsatellite markers, cosegregation
      analysis indicated that Dp-1 is flanked by NH006b and NH014a on linkage group 17,
      2.3 and 3.6 cM away, respectively. Evidence is also presented for the duplication
      of linkage groups 9 and 17, which is a consequence of the allopolyploid origin of
      pear.

PMID- 19088816
TI  - Integrative genomic and gene expression analysis of chromosome 7 identified novel
      oncogene loci in non-small cell lung cancer.
AB  - Lung cancer accounts for over a quarter of cancer deaths, with non-small cell
      lung cancer (NSCLC) accounting for approximately 80% of cases. Several genome
      studies have been undertaken in both cell models of NSCLC and clinical samples to
      identify alterations underlying disease behaviour, and many have identified
      recurring aberrations of chromosome 7. The presence of recurring chromosome 7
      alterations that do not span the well-studied oncogenes EGFR (at 7p11.2) and MET
      (at 7q31.2) has raised the hypothesis of additional genes on this chromosome that
      contribute to tumourigenesis. In this study, we demonstrated that multiple loci
      on chromosome 7 are indeed amplified in NSCLC, and through integrative analysis
      of gene dosage alterations and parallel gene expression changes, we identified
      new lung cancer oncogene candidates, including FTSJ2, NUDT1, TAF6, and POLR2J.
      Activation of these key genes was confirmed in panels of clinical lung tumour
      tissue as compared with matched normal lung tissue. The detection of gene
      activation in multiple cohorts of samples strongly supports the presence of key
      genes involved in lung cancer that are distinct from the EGFR and MET loci on
      chromosome 7.

PMID- 19088817
TI  - Pink1 suppresses alpha-synuclein-induced phenotypes in a Drosophila model of
      Parkinson's disease.
AB  - Parkinson's disease (PD) is the most prevalent human neurodegenerative movement
      disorder and is characterized by a selective and progressive loss of the
      dopaminergic neurons. Mutations in the genes parkin and PTEN-induced putative
      kinase 1 (PINK1) result in autosomal recessive forms of PD. It has been suggested
      that parkin and Pink1 function in the same pathway in Drosophila, with Pink1
      acting upstream of parkin. Previous work in our laboratory has shown the ability
      of parkin to rescue an alpha-synuclein-induced PD-like phenotype in Drosophila.
      To investigate the ability of Pink1 to protect against alpha-synuclein-induced
      toxicity, we have performed longevity, mobility, and histological studies to
      determine whether Drosophila Pink1 can rescue the alpha-synuclein phenotypes. We
      have found that overexpression of Pink1 results in the rescue of the alpha
      synuclein-induced phenotype of premature loss of climbing ability, suppression of
      degeneration of the ommatidial array, and the suppression of alpha-synuclein
      induced developmental defects in the Drosophila eye. These results mark the first
      demonstration of Pink1 counteracting PD phenotypes in a protein toxicity animal
      model, and they show that Pink1 is able to impart protection against potentially
      harmful proteins such as alpha-synuclein that would otherwise result in cellular
      stress.

PMID- 19088818
TI  - Phylogenetic relationships between annual and perennial species of Helianthus:
      evolution of a tandem repeated DNA sequence and cytological hybridization
      experiments.
AB  - The amplification and chromosomal localization of tandem repeated DNA sequences
      from Helianthus annuus (clone HAG004N15) and the physical organization of
      ribosomal DNA were studied in annual and perennial species of Helianthus.
      HAG004N15-related sequences, which did not show amplification in other Asteraceae
      except for Viguiera multiflora, were redundant in all the Helianthus species
      tested, but their frequency was significantly higher in perennials than in
      annuals. These sequences were located at the ends and intercalary regions of all
      chromosome pairs of annual species. A similar pattern was found in the
      perennials, but a metacentric pair in their complement was not labelled.
      Ribosomal cistrons were carried on two chromosome pairs in perennials and on
      three pairs in annuals except for H. annuus, where rDNA loci were on four pairs.
      No difference was observed between cultivated H. annuus and its wild accessions
      in the hybridization pattern of the HAG004N15 and ribosomal probes. These
      findings support the hypothesis that the separation between annual and perennial
      Helianthus species occurred through interspecific hybridization involving at
      least one different parent. However, GISH in H. annuus using genomic DNA from the
      perennial Helianthus giganteus as blocking DNA failed to reveal different genomic
      assets in annual and perennial species.

PMID- 19088819
TI  - A note on the bias of genetic distances in linkage maps based on small samples
      for backcrosses and intercrosses with complete dominance.
AB  - This paper investigates the bias (the difference between the expectation (mean)
      of an estimator and its true value) of genetic distances for small samples. Exact
      results on this bias have not received much attention in genetic mapping
      literature. We show that bias drops quickly with increasing sample size for both
      a backcross population and an F2 in coupling. By contrast, bias may be
      substantial even for larger sample size for an F2 when markers are in repulsion.
      It is concluded that Karlin's map function should be used with care when mapping
      is done using an F2 population. The same note of caution applies to other map
      functions such as Haldane's and Kosambi's. Finite-sample bias of these latter
      functions cannot be assessed because of the nonexistence of an expected value,
      but their median bias is similar to that of Karlin's function.

PMID- 19088820
TI  - Comment on "Comparative genomic analysis of the whale (Pseudorca crassidens) PRNP
      locus".
AB  - A reminder that another paper on the cetacean PRNP locus has been published
      before Kim et al.'s paper (2008. Genome, 51: 452-464) is presented along with a
      consideration of the related results.

PMID- 19088821
TI  - Hendrik Peter Bernelot Moens (1931-2008).
AB  - The synaptonemal complex (SC) is a proteinaceous structure that physically holds
      the two homologous chromosomes together during meiotic prophase. First observed
      in 1956 by Montrose J. Moses (Duke University, Durham, North Carolina) in meiotic
      prophase spermatocytes of crayfish, the SC was found in many other species.
      Initially, the research into the SC focused on its structural characteristics,
      but with the availability of antibodies, the focus shifted to the protein
      components of the complex, and later, attention was diverted to the proteins
      associated with this structure at different time points during meiotic prophase.
      Various possible roles of this meiotic-specific structure have been debated since
      the discovery of the SC structure but consensus has yet to be reached. Dr. Peter
      Moens has been an internationally recognized expert on the SC, being involved in
      all of the steps and characterizing many of the structural and functional
      components of the complex mainly in mice but also in other species.

PMID- 19088822
TI  - [Cloning deletion of mouse medullary CD4SP thymocyte subgroups induced by
      superantigen staphylococcal enterotoxin B].
AB  - OBJECTIVE: To investigate the clonal deletion of medullary CD4SP thymocyte
      subgroups induced by superantigen SEB, and to understand the stage specificity of
      thymic negative selection based on the developmental pathway of medullary CD4SP
      thymocytes we established previously. METHODS: SEB was intravenously injected
      into C57BL/6 mice, and then the expression of surface molecules and apoptosis of
      thymocytes were detected by FACS. The reduction of each subgroup of medullary
      CD4SP thymocytes was analyzed by FACS assay and cell counting. RESULTS: The
      percentage of apoptotic CD4SP thymocytes significantly increased after the
      intravenous injection of SEB. The cell number of CD4SP decreased about 43.8%.
      Among TCR Vbeta8(+)CD4SP thymocytes, the percentage of 6C10(+)CD69(+)Qa-2(
      )thymocytes(SP1) was reduced by two thirds and the percentage of Qa-2(+)
      thymocytes(SP4) was comparatively increased, while the cell numbers of SP1 to SP3
      decreased over 80% and that of SP4 decreased about 50%. CONCLUSION: Thymic
      negative selection occurs during the stage of SP and goes through the whole
      developmental progress from SP1 to SP4.The thymocytes in the stage of SP1 to SP3
      are more sensitive to apoptosis than those in the stage of SP4.

PMID- 19088824
TI  - [Overexpression of programmed cell death 5 factor enhances triptolides-induced
      fibroblast-like synoviocytes apoptosis in rheumatoid arthritis].
AB  - OBJECTIVE: To explore the effect of programmed cell death 5(PDCD5) on apoptosis
      of rheumatoid arthritis fibroblast-like synoviocytes(RA FLS) induced by
      triptolide. METHODS: Cultured synovial cells in vitro from RA patients were
      transfected with Ad-PDCD5.At protein level, expression of PDCD5 in RA FLS
      infected with Ad-PDCD5 was detected by Western blot.RA FLS infected with Ad-PDCD5
      were cultured in presence or absence of triptolide and apoptosis of RA FLS was
      determined by flow cytometry. RESULTS: Infection of RA FLS with increasing
      concentrations of Ad-PDCD5(50-300 MOI) resulted in a does-dependent increase in
      the production of PDCD5. Apoptotic cells percentage for noinfection group, Ad
      null group and Ad-PDCD5 group were(22.41 +/- 3.87)%, (28.77 +/- 12.97)% and
      (48.87 +/- 12.69)%, respectively. Alternatively, infection without addition of
      triptolide stimuli had no effect. The data showed that gene transfection of PDCD5
      alone without addition of triptolide was not sufficient to activate RA FLS
      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- 19088823
TI  - [Mucosal administration of altered CII263-272 peptide inhibits collagen-induced
      arthritis].
AB  - OBJECTIVE: To evaluate the effect of mucosal administration of altered collagen
      II(CII)263-272 peptide (267Q-->A, 270K-->A and 271G-->A) on collagen induced
      arthritis (CIA), and to explore the mechanism of the inhibitory effect of the
      altered CII263-272 peptide on CIA. METHODS: CIA was induced in Lewis rats by
      immunization with bovine CII. Altered CII263-272 peptide was given intranasally
      beginning from the onset of arthritis (100 microg/dose, daily for 5 doses and
      continuing every other day for other 7 doses). Wild CII263-272 peptide (100
      microg/dose) or PBS was administered as controls with the same procedure.
      Therapeutic effects were evaluated by arthritis scores, body weight change, and
      joint pathologic scores. The anti-CII antibody and its subtypes were measured
      with ELISA. The cytokines of IFN-gamma and IL-10 were measured with ELISA. The
      induction of regulatory T cells was assessed by FACS analysis of percentage of
      peripheral CD4(+)CD25(+) T cells, and by real-time PCR analysis of the expression
      of Foxp3 and TGF-beta mRNA. RESULTS: (1) Following treatment with the altered
      CII263-272 peptide, arthritis scores were reduced and body weight was increased.
      The mean arthritis scores of rats treated with altered peptide, wild peptide and
      PBS were 2.50 +/- 2.43, 4.50 +/- 2.23 and 6.33 +/- 2.73, respectively. The
      altered peptide could retard the histologic lesion of the joints. (2) The titers
      of anti-CII antibodies IgG and IgG1 in the three groups were similar, but the
      IgG2a in altered peptide-treated rats decreased markedly as compared with PBS
      treated rats (0.56 +/- 0.19 vs 0.95 +/- 0.29, P<0.05). The serum IFN-gamma in
      rats treated with altered peptide, wild peptide and PBS were (185.33 +/- 29.77),
      (231.62 +/- 41.82) and (220.64 +/- 83.61) ng/L, respectively (P<0.05). No
      difference was found in the levels of serum IL-10 among the three groups. (3)
      There was no significant difference in the percentage of peripheral CD4(+)CD25(+)
      T cells and the expression level of Foxp3 and TGF-beta mRNA. CONCLUSION: Mucosal
      administration of altered CII263-272 peptide could effectively inhibit the
      progression of CIA. It can decrease the IgG2a subtype of anti-CII antibodies and
      IFN-gamma, and inhibit Th1 response in vivo. Altered C II263-272 peptide may be
      therapeutic for RA.

PMID- 19088825
TI  - [Both PIK3IP1 and its novel found splicing isoform, PIK3IP1-v1, are located on
      cell membrane and induce cell apoptosis].
AB  - OBJECTIVE: To find novel isoform of PIK3IP1 and analyze their effects on cell
      viability, subcellular localization, and expression profile in cell lines.
      METHODS: RT-PCR was used to clone PIK3IP1 and its novel splicing isoform PIK3IP1
      v1 from multi-tissue cDNA pool. By cell-based assays, we studied how PIK3IP1 and
      PIK3IP1-v1 affected the activity of Renila luciferase and morphological change in
      the HEK 293T cells. Furthermore, flow cytometry experiment was used to validate
      that overexpression of both splicing isoforms could induce cell apoptosis.
      Bioinformatics analysis was used to identify structural characteristics of these
      two splicing isoforms. By fluorescence microscopy assay, we identified their
      subcellular localization. RT-PCR was used to detect the expression of PIK3IP1 in
      the cell lines. RESULTS: PIK3IP1 and its novel splicing isoform PIK3IP1-v1 were
      cloned and constructed into the pcDNA-and pEGFP-expression plasmids. They both
      had signal peptide and transmembrane domain. Nevertheless, PIK3IP1-v1 was in
      absence of an extracellular Kringle domain. They could inhibit the activity of
      Renila luciferase and induce cell apoptosis. Simultaneously, both splicing
      isoforms are validated with subcellular localization on cell membrane and lowly
      expressed in many cell lines. CONCLUSION: PIK3IP1-v1 is a novel splicing isoform
      of PIK3IP1. Both of them are located on cell membrane and can induce cell
      apoptosis.

PMID- 19088826
TI  - [Tumor necrosis factor-alpha upregulates the protein levels of adipose
      differentiation-related protein in rat differentiated adipocytes].
AB  - OBJECTIVE: To investigate the effect and basis of tumor necrosis factor-alpha
      (TNF-alpha) on the lipid droplet associating protein adipose differentiation
      related protein(ADRP) in rat differentiated adipocytes. METHODS: Differentiated
      rat adipocytes derived from epididymal fat pads of Sprague-Dawley rats were
      incubated in the presence or absence of TNF-alpha (25 microg/L). Glycerol level
      released in the culture medium was determined by a colorimetric assay and served
      as an index of lipolysis. The protein levels of two lipid droplet associating
      proteins, perilipin and adipose differentiation-related protein, were examined by
      immunoblotting analysis. The intracellular lipid droplets were stained by nile
      red and the localizations of perilipin and ADRP on the lipid droplets were
      determined by immunostaining. RESULTS: On day 5 or day 8 after the
      differentiation of adipocytes, TNF-alpha significantly stimulated lipolysis. The
      lipolysis response to TNF-alpha occurred apparently at hour 8 and remained high
      48 h after the stimulation. TNF-alpha increased the protein levels of ADRP,
      downregulated perilipin proteins but promoted its phosphorylation level. TNF
      alpha caused the lipid droplet dispersion, whereas ADRP and perilipin proteins
      were remained to associate with the surface of the dispersed lipid droplets.
      CONCLUSION: Chronic stimulation of lipolysis by TNF-alpha resulted in the
      dispersion of the lipid droplets and therefore upregulated the levels of ADRP
      proteins.

PMID- 19088827
TI  - [Expression of MMP-2 and its clinical significance in cervical squamous
      carcinoma].
AB  - OBJECTIVE: To investigate the relationship of the expression of matrix
      metalloproteinase-2 (MMP-2) with tumorigenesis, development and metastasis of
      cervical squamous carcinoma. METHODS: The expression and distribution of MMP-2
      protein were detected by using immunohistochemical SP method. The active protein
      and mRNA of MMP-2 were determined by using gelatin Zymography and RT-PCR,
      respectively. The relationships between those indexes and the factors related to
      clinical pathology of cervical carcinoma were analyzed statistically. RESULTS:
      Immunohistochemical studies demonstrated that MMP-2 was expressed in 81.13% of
      squamous cell carcinomas (SCC), but was less frequently expressed in high-grade
      squamous intraepithelial lesions (HSIL, 47.62%, 10/21) and low-grade squamous
      intraepithelial lesions (LSIL, 10.00%, 1/10, P<0.01). In SCC, MMP-2 protein was
      expressed in 91.30%(21/23) of patients, which positively correlated with lymph
      node metastasis significantly (P<0.05). And the expression of MMP-2 was not
      significantly related to the pathological grade, or stage status. By direct
      analysis of enzyme activities we found that the gelatinolytic activity of MMP-2
      was significantly higher in SCC [(5.81 +/- 2.17)x10(4)] than in HSIL [(2.28 +/-
      0.83) x10(4), P<0.01] and LSIL [(1.94 +/- 0.71)x10(4), P<0.01]. Expression of MMP
      2 mRNA was significantly higher in carcinoma(0.87 +/- 0.44) than in HSIL(0.46 +/-
      0.22, P<0.01) and in LSIL(0.37 +/- 0.20, P<0.01). CONCLUSION: The positive
      expression of MMP-2 can be used to estimate the metastatic potentiality and help
      the adjuvant treatment. MMP-2 is related well with the occurrence, invasion and
      metastasis of cervical squamous carcinoma.

PMID- 19088828
TI  - [Establishment of a podocyte cell injury model induced by puromycin
      aminonucleoside].
AB  - OBJECTIVE: To establish a podocyte cell injury model induced by puromycin
      aminonucleoside (PAN), an in vitro model for studying the role of podocytes,
      especial the slit diaphragm molecules in proteinuria at the cellular and
      molecular levels. METHODS: MPC5 were treated for 24 and 48 hours by 15, 45 and 75
      mg/L PAN, respectively. The podocyte molecular behavior during podocyte injury
      was evaluated: the apoptotic podocyte cells were revealed with FITC-Annexin V and
      Propidium Iodide (PI) assay and the proliferative podocyte cells detected with
      MTT assay after PAN treatment. The distribution of Nephrin and Podocin was
      revealed with indirect-immunofluorescent staining under confocal microscope. The
      distribution of F-actin was revealed with direct-immunofluorescent staining under
      microscope. RESULTS: The percentage of apoptotic podocyte cells was increased in
      a dose- and time-dependent manner after PAN treatment. In PAN-treated group, the
      apoptosis was obviously increased at hour 48, the PAN-45 treated group was 33.48%
      +/- 14.55% and PAN-75 treated group 38.01% +/- 12.13% vs the control group 6.38%
      +/- 0.50% (P<0.01). CONCLUSION: We set up an in vitro podocyte injury model
      treated with PAN for the first time. This reliable cell model is a good basis for
      further studies on podocyte injury.

PMID- 19088829
TI  - [Study on the mechanism of insulin resistance in rats born with intrauterine
      growth retardation].
AB  - OBJECTIVE: To investigate the expressions of the insulin receptor (IR), insulin
      receptor substrate-1 (IRS-1), insulin receptor substrate-2 (IRS-2), phosphatidyl
      inositol 3-kinase (PI3K) and insulin-like growth factor-1 (IGF-1) of the livers
      of the male adult rats born with intrauterine growth retardation (IUGR),and to
      find out the relationship between IUGR and insulin resistance in their adult
      life. METHODS: The foods were available ad libitum throughout the pregnancy to
      the control group and the rats in the experimental group were fed 50% of the
      control group to build the IUGR animal model. Liver samples were collected when
      the male offspring grew up to 12 weeks old. The mRNA expressions of hepatic IR,
      IRS-1, IRS-2, PI3K, and IGF-1 were detected by RT-PCR. The protein expressions of
      hepatic IR, IRS-1, and IRS-2 were analyzed by immunohistochemistry. RESULTS: The
      mRNA expressions of hepatic IR in the adult male rats with IUGR were
      significantly lower than control group [(0.41+/-0.06) vs (0.62+/-0.11), P<0.05].
      But the expressions of hepatic IR protein were similar [(6.21+/-0.57) vs (6.69+/
      0.47), P>0.05] in both groups. The mRNA and protein expressions of the hepatic
      IRS-1 [mRNA: (0.77+/-0.20) vs (1.32+/-0.42), P<0.05; protein: (2.15+/-0.23) vs
      (5.96+/-0.38), P<0.05] and IRS-2 [mRNA: (1.05+/-0.28) vs (1.48+/-0.40), P<0.05;
      protein: (4.33+/-0.29) vs (7.08+/-0.35), P<0.05] of the IUGR rats were reduced;
      there were no differences between the hepatic PI3K mRNA expressions in the 2
      groups [(1.12+/-0.19) vs (1.18+/-0.24), P>0.05]. The expressions of hepatic IGF-1
      mRNA of the rats with IUGR were significantly lower than those in control group
      [(0.55+/-0.12) vs (1.22+/-0.34), P<0.05]. There was close relation between the
      reduction of the expression of hepatic IGF-1 mRNA and the expression of IRS-1
      mRNA (r=0.821, P<0.05) and IRS-2 mRNA(r=0.643, P<0.05) in the adult male rats
      with IUGR. CONCLUSION: The reduced expressions of IRS-1 and IRS-2 caused the
      lower expression of hepatic IGF-1 in the adult male rats with IUGR, which was
      related to the stunted growth and the insulin resistance. There were no relation
      of the expressions of hepatic IR and PI3K and the insulin resistance in adult
      male rats with IUGR.

PMID- 19088830
TI  - [Idiopathic pulmonary hemosiderosis in adults: report of two cases and literature
      review].
AB  - OBJECTIVE: To describe the clinical, radiological and pathological
      characteristics of idiopathic pulmonary haemosiderosis (IPH) in adults and to
      evaluate the methods of diagnosis and treatment. METHODS: Two patients were
      successfully diagnosed and treated in our hospital and the literature on the
      subject was reviewed. RESULTS: Two adult patients (19 and 34 years old) diagnosed
      in our hospital had 5 and 10 years of history of hemoptysis respectively, and
      chest CT showed bilateral diffuse alveolar opacities over mid and lower zones.
      Tests of antinuclear antibodies (ANAs), rheumatoid factor (RF), antineutrophilic
      cytopasmic antibodies (ANCA) and Anti-glomerular basement membrane (anti-GBM)
      antibody were negative. Haemosiderin-laden macrophages were found in
      bronchoalveolar lavage fluid (BALF) whose color was yellow. Microscopic
      examination of the lung tissue specimens obtained by transbronchial lung biopsy
      (TBLB) revealed hemorrhage and numerous hemosiderin-laden macrophages in the
      alveoli and no vasculitis or capillaritis were seen. These findings were
      consistent with a diagnosis of IPH. Steroid therapy had good effects. CONCLUSION:
      IPH is a diagnosis of exclusion of other causes of diffuse alveolar hemorrhage
      (DAH). IPH adults have relatively good drug responses and relatively good
      prognoses.

PMID- 19088831
TI  - [Medical thoracoscopic talc pleurodesis for malignant pleural effusion: an
      analysis of 27 cases].
AB  - OBJECTIVE: To evaluate the efficacy and safety of talc poudrage pleurodesis via
      semi-rigid medical thoracoscopy in the treatment of malignant pleural effusions,
      as well as the factors that may influence the outcomes. METHODS: A series of 27
      patients with malignant pleural effusion underwent medical thoracoscopic talc
      poudrage pleurodesis between July 2005 and September 2007 in Peking University
      First Hospital. RESULTS: There were 16 male and 11 female patients in the series,
      the average age being 65.2 years. All the patients had documented malignant
      pleural effusions, including 16 cases of adenocarcinoma, 6 of malignant
      mesothelioma, 2 of squamous cell carcinoma, 1 of lymphoepithelioma-like
      carcinoma, 1 of small cell carcinoma and 1 of undifferentiated lung cancer.
      Thirty days after the procedures, complete successful pleurodesis was achieved in
      22 cases, and partial successful in 4 cases. Pleurodesis was not successful in
      one case. Overall successful rate was 96.3% (26/27). The average duration of
      thoracic tubing was 6.85 days. Chest pain, fever and an increase in peripheral
      WBC after the procedure occurred in 19(70.4%, 19/27), 21(77.8%, 21/27), and
      12(44.4%, 12/27) cases respectively. No respiratory failure occurred. CONCLUSION:
      Medical thoracoscopic talc poudrage pleurodesis is a safe and effective method
      for the treatment of malignant pleural effusion.

PMID- 19088832
TI  - [Meta-analysis of beta-adrenoceptor blockers for the treatment of vasovagal
      syncope].
AB  - OBJECTIVE: To summarize present randomized controlled trials and assess the
      effect of beta-adrenoceptor blockers on vasovagal syncope using meta-analysis
      method. METHODS: According to inclusion and exclusion criteria, articles were
      selected from medical electronic databases searching, including PubMed (1968
      2007), EMBASE (1991-2007), Elsevier (1990-2007) and CNKI (1990-2007). Randomized
      controlled trials (RCTs) were assessed based on the Juni assessment. Meta
      analysis was completed using software Review Manager 4.2. Indication for
      evaluating effect was recurrence of syncope during follow-up or response in head
      up tilt test (HUT). The results were stated as relative risk (RR) or odd ratio
      (OR) and their 95% confidence interval (CI), and P<0.05 showed significant
      differences. RESULTS: Thirteen RCTs were selected finally. Funnle polt analysis
      showed publication bias might exist. Meta-analysis of 11 RCTs, including totally
      460 patients in treatment group and 371 patients in control group, indicated
      patients in treatment group had lower rate of syncope recurrence as compared with
      control group (RR=0.61, 95%CI: 0.39-0.96, P=0.03). From 7 RCTs, including 166
      patients in treatment group and 163 in control group, meta-analysis explored that
      patients in treatment group had higher rate of negative response in HUT at the
      end-point of follow-up as compared with control group (OR=9.15, 95%CI: 3.75
      22.31, P<0.01). CONCLUSION: The currently published RCTs support that beta
      adrenoceptor blockers can be effective treatment of vasovagal syncope though the
      medicine was supposed to be not useful according to some well controlled studies.
      So, further large-scale multicentre and better designed study were still expected
      to give more convincing evidence.

PMID- 19088833
TI  - [Influence of disulfiram on the expression of transforming growth factor-beta2 in
      form-deprived eyes in chicks].
AB  - OBJECTIVE: To explore the temporal expression of retinal-choroidal transforming
      growth factor-beta2 (TGF-beta2) in form-deprived myopia (FDM) chick eyes and
      study the effect of an inhibitor (disulfiram, DSF) of retinoid acid (RA)
      synthesis on refractive development and the expression of TGF-beta2. METHODS:
      Ninety new hatched white leghorn chicks were divided randomly and equally into 3
      groups: unilateral occluded with frosted goggles (Group A); unilateral
      intravitreal injection of 4 mmol of the non-specific aldehydedehydrogenase
      inhibitor disulfiram with further treatment with goggles (Group B); unilateral
      intravitreal injections of 4 mmol of disulfiram without further treatment with
      goggles (Group C). Refraction and axial length were measured on 1, 7 and 14 days
      after treatment. Expression levels of TGF-beta2 and TGF-beta2 mRNA in the retinal
      choroid layer were analyzed by immunohistochemistry and real-time RT-PCR.
      RESULTS: In Group A, the form-deprived eyes made by goggles developed myopia
      (P<0.05 on day 1, P<0.01 on days 7 and 14, compared with the contralateral eyes)
      with a lengthening of the axial length (P<0.01 on days 7 and 14, compared with
      the contralateral eyes), as well as a lower level of TGF-beta2 expression (P<0.01
      on days 7 and 14, compared with the contralateral eyes). In Groups B and C, there
      was no statistically significant difference in refraction and axial length
      between treated and contralateral eyes (P>0.05) with TGF-beta2 mRNA level growing
      on day 7 and decreased on day 14 in group B and decreased on day 1, increased on
      days 7 and 14 in Group C (P<0.01, compared with the contralateral eyes).
      Immunohistochemistry showed that the expression of TGF-beta2 was mainly changed
      in the outer part of photoreceptor layer and retinal pigment epithelium (RPE)
      layer. CONCLUSION: TGF-beta2 mRNA level decreased in FDM eyes. Disulfiram can up
      regulate the level of TGF-beta2 mRNA expression in the posterior retinal-choroid,
      and inhibit the elongation of axial length and refractive error made by frosted
      goggles as well. Disulfiram which inhibits the synthesis of retinoid acid may
      suppress deprivation myopia by up-regulating the expression level of TGF-beta2
      mRNA.

PMID- 19088834
TI  - [Expression of genes related to Sonic Hedgehog signaling in human hepatocellular
      carcinomas].
AB  - OBJECTIVE: To investigate the expression status of Sonic Hedgehog signaling genes
      and molecules in human hepatocellular carcinomas(HCC), and to explore the
      relationship between these genes and clinical prognosis. METHODS: HCC tissue and
      adjacent normal tissue from 29 HCC patients were assayed for the expression of
      hedgehog signaling genes by reverse transcription-polymerase chain reaction chain
      reaction (RT-PCR) techniques and for the expression of hedgehog signaling
      molecules by immunohistochemistry. The expressions of Shh, Ptch, Smoh, Gli-1 mRNA
      were assayed as well as Shh, Ptch proteins in 29 cases of HCC and in 29 liver
      tissues adjacent to the tumor. RESULTS: Expression of Shh mRNA was detectable in
      about 51% of HCCs examined. Consistent with this, hedgehog target genes Ptch,
      Smoh and Gli-1 mRNA were expressed in over 68%, 48% and 62% of the tumors,
      respectively, and the expressions of Shh and Ptch proteins in HCC tumor tissues
      correlated with those of Shh and Ptch mRNA in tumor tissues (P=0.041 and
      P=0.035). This suggested that the hedgehog pathway was frequently activated in
      HCCs. The simultaneous expression of Gli-1 in HCC and liver tissues adjacent to
      the tumor had significantly relationship with poor prognosis. CONCLUSION:
      Hedgehog signaling activation is an important event for development of human
      HCCs. It also suggests that markers for hedgehog signaling activation may be
      useful for the determination of prognosis.

PMID- 19088835
TI  - [Study on human neural stem cells differentiation in vitro and transplantation in
      nude mice].
AB  - OBJECTIVE: To investigate the differentiation of human neural stem cells (hNSCs)
      in vitro and to assess the potential of hNSCs transplanted into the pylorus of
      nude mice. METHODS: Central nervous system-derived hNSCs (CNS-hNSCs) were
      obtained from the subventricular zone of aborted fetus brain (10 weeks),
      suspension cultured, passaged and induced to differentiate in vitro. Stem cell
      marker neuroepithelial stem cell protein (nestin), enteric neuronal marker
      protein gene production 9.5 (PGP9.5) and glial cell marker glial fibrillary
      acidic protein (GFAP) were detected by immunofluorescence method. CNS-hNSCs
      (cultured for 3 months) were transplanted into the pylorus of nude mice and
      followed by immunofluorescence method. RESULTS: Using the immunofluorescence
      method, nestin could be identified and the induced cells expressed PGP9.5 and
      GFAP. After being transplanted into the pylorus of nude mice, CNS-hNSC could be
      detected to survive at least for 6 weeks. CONCLUSION: CNS-hNSCs could be
      cultured, passaged and induced in vitro successfully; transplantation of CNS
      hNSCs into gastrointestinal tract could be a potential cellular replacement
      strategy for gastrointestinal motility disorders.

PMID- 19088836
TI  - [Progression rate of MUNE at diagnosis: a prognostic factor of survival in
      patients with amyotrophic lateral sclerosis].
AB  - OBJECTIVE: To identify the correlation between the progression rate of motor unit
      number estimate (MUNE) at diagnosis and survival. METHODS: We included 129
      patents with amyotrophic lateral sclerosis (ALS) enrolled in our hospital from
      January 2002 to December 2005. We recorded clinical features, ALS functional
      rating scale (ALSFRS), forced vital capacity (FVC) and electrophysiological data
      at diagnosis. The patients were monitored every 3 months from visit to death or
      tracheotomy. RESULTS: Mean age at onset was (52.19+/-11.00) years. The median
      survival time from symptom onset was 45.71 months (95% CI=35 to 51). In
      univariate analysis of Kaplan-Meier method, outcome was significantly related to
      progression rate of MUNE (P<0.05). In the Cox multivariate model, progression
      rate of MUNE was a significant prognostic factor of survival (P<0.01). Using
      2.9/month as cutoff point, the value beyond this point at diagnosis tended to
      have a shorter survival (P<0.05). A 1-unit decrease in the progression rate of
      MUNE was associated with a 34.2% decrease risk of death. CONCLUSION: Progression
      rate of MUNE at diagnosis can provide the information of disease progression at
      one particular point, which may help to stratify patients and affect survival. It
      is the strongest prognostic factor of survival in patients with ALS compared with
      age, onset site and time from onset to diagnosis.

PMID- 19088837
TI  - [Long-term changes of hard-tissue in borderline cases with extraction vs. non
      extraction treatment].
AB  - OBJECTIVE: To investigate hard-tissue changes in borderline cases with extraction
      and non-extraction during treatment and follow-up stages. METHODS: Five associate
      professors, who were from Peking University School and Hospital of Stomatology,
      were asked to make judgment on the cases with full pre-treatment records for
      discriminating the borderline cases from extraction and non-extraction cases.
      Fifty-four borderline cases with full treatment records which had been out of
      treatment for at least 2 years were followed. Twenty-one cases with follow-up
      records were collected including 8 extraction cases and 13 non-extraction cases.
      Cephalometric measurements were preceded in IDAS (Image and Database Analysis
      System) software program. RESULTS: In extraction group, significant changes of
      SNB, SNPg in A-P direction and that of ArGo/ANSMe, MP/SN in vertical direction
      were present during the follow-up stage, while the overjet was stable. In non
      extraction group, only decrease of proclination of lower incisor and increase of
      overjet were present without any skeletal changes during the follow-up stage. In
      comparison of the two groups, no skeletal and dental changes showed statistically
      significant difference except for MP/SN and ArGoGn in pre-treatment stage, while
      dental characteristics in relation to upper and lower incisor (L1/NB, L1-NB, L1
      AP, U1-AP, U1/L1) showed statistically significant difference between the two
      groups after treatment. But in follow-up stage, the skeletal and dental pattern
      tended to be similar for both groups only except for the proclination of lower
      incisor. CONCLUSION: The similarities of skeletal and dental pattern are
      demonstrated in extraction and non-extraction group before treatment. Dental
      changes are the major post-treatment changes in the two groups. In follow-up
      stage, counter-clockwise rotation of mandible is unique in extraction group,
      which is likely a helpful factor for stability of overjet, while lingual tipping
      of lower incisor in non-extraction group without skeletal changes may contribute
      to overjet relapse.

PMID- 19088838
TI  - [Evaluation of diagnostic sensitivity of electroneurography for facial
      neurotmesis].
AB  - OBJECTIVE: To evaluate diagnostic sensitivity of electroneurography (ENoG) for
      facial neurotmesis. METHODS: The data of 24 patients suffering from facial
      neurotmesis on one side, having non-emergency operation, and having preoperative
      records of ENoG were collected. Among the patients, 18 were men and 6 were women,
      aged from 3 to 55 years (median 28). The duration of injury before ENoG
      examination was from 1 to 56 days (mean 23.6 days) for them. The
      electroneurographic examination was carried out for facial nerves on both sides
      preoperatively. Percentages of evoked potential amplitude reduction on affected
      sides were calculated according to the value of normal side. The 90% reduction of
      amplitude was used as a cutting point. The facial neurotmesis was observed during
      operation. The sensitivity and false negative proportions of ENoG were analyzed.
      RESULTS: Among the 24 patients with facial neurotmesis, 22 had ENoG amplitude
      reduction over 90%, and 2 having this reduction less than 90%. The sensitivity
      and false negative proportions of ENoG in patients with facial neurotmesis were
      91.7% and 8.3% respectively. CONCLUSION: The preoperative ENoG examination is
      high sensitivity for facial neurotmesis. The patients whose ENoG reduction over
      90% should be advised to have a facial neurorrhaphy as soon as possible.

PMID- 19088839
TI  - [Intravenous leiomyomatosis with intracardiac extension: a case report].
AB  - Intravenous leiomyomatosis is characterized by a proliferation of benign smooth
      muscular tissue growing into uterine with malignant appearance. On extremely rare
      occasions, the tumor may grow out of the pelvis and extend into the inferior vena
      cava and the right atrium. We report a case of intravenous leiomyomatosis
      extending into the right atrium. A 41-year-old woman complained of 20 days of
      intermittent abdominal pain and lower limbs swell. Medical history of the patient
      revealed a previous hysterectomy operation 3 years ago due to uterine leiomyoma.
      Echocardiography showed a homogenous mass extending from the inferior vena cava
      to the right atrium, without evidence of adherence to the right atrial wall, the
      left ventricular ejection fraction was only 60%. Computer tomography showed that
      a large mass arising from the left internal iliac vein and extending into the
      right chambers. Pelvic vascular ultrasound revealed the thrombotic material in
      the inferior vena cava and the left common iliac vein, and confirmed the presence
      of a complex mass in the left annex region. Based on the findings, the initial
      diagnosis was intracardiac and intravenous tumor. An operation was performed
      through a sternotomy and laparotomy to remove the whole tumor from the left
      common iliac vein to the right atrium, ligate left internal iliac vein mean-wile.
      No hormonal therapy was administrated after the operation. Immunohistochemical
      studies revealed that the tumor cells were fusiform shape, there was no
      karyokinesis and necrosis, and the tumor cells were positive for smooth muscle
      antigen and desmin, as well as estrogen receptor and progesterone receptor. Six
      months postoperation follow-up revealed no signs of recurrence. The differential
      diagnosis of the disease compared with primary cardiovascular sarcomas and
      thrombus was difficult. The final diagnosis relied on immunohistochemical
      analysis, however, the short-term result of operation was acceptable.

PMID- 19088840
TI  - [Congenital bilateral perisylvian syndrome: a case report].
AB  - Congenital bilateral perisylvian syndrome (CBPS) is rare in literature,
      especially in China. In this article, we report the clinical and treatment of a
      patient with CBPS and discuss its mechanism, clinical features and therapy. This
      patient was a 28-year-old man. His main clinical features were pseudobulbar
      palsy, cognitive deficits and intractable epilepsy. MRI shows bilateral
      thickening of the cortex around the sylvian fissures which were deeper than
      normal and polymicrogyria. The electroencephalogram demonstrated slow spike in
      right temporal lobe and left frontal lobe. Rhythmal 4 Hz theta waves exist in
      left frontal and parietal lobe. As the epilepsy was poorly controlled by
      antiepileptic, section of the corpus callosum was carried out. After callosotomy,
      there was pronounced seizure reduction and intelligence development improvement.
      CBPS is characterized by pseudobulbar palsy, cognitive deficits, and bilateral
      perisylvian abnormalities in imaging studies. If intractable epilepsy is
      combined, callosotomy may be effective.

PMID- 19088841
TI  - [Muscle atrophy of hand as an initial sign in a patient with protoplasmic
      astrocytoma: a case report and literature review].
AB  - We reported a rare case of protoplasmic astrocytoma presenting small muscle
      atrophy of the right hand as an initial sign. A 39-year-old male was admitted to
      hospital complaining of chronic muscle atrophy and subtle headache.
      Electromyography (EMG) showed brief small denervation and no signs of sensory
      motor conduction impairment. CT and MRI revealed multiply expansive intracranial
      lesion in left hemisphere, which was highly suspected of cerebral echinococcus or
      Balo disease. The patient underwent surgical excision and pathological report was
      protoplasmic astrocytoma, with glial fibrillary acidic protein (GFAP, +++) of
      immunohistochemical method. We reviewed clinical features, radiological
      manifestations and pathology of protoplasmic astrocytoma with medical literature
      documents.

PMID- 19088842
TI  - [One case report of SAPHO syndrome and literature review].
AB  - To study the clinical features and diagnosis of synovitis, acne, pustulosis,
      hyperostosis, osteitis syndrome (SAPHO) syndrome. One case of SAPHO syndrome was
      reported and the related data of SAPHO syndrome were reviewed. The main clinical
      features of the patient were articulatio carpi synovitis, acne, cervical rib
      hyperostosis, articulatio sternoclavicularis and osteitis, So the diagnosis of
      SAPHO syndrome was made. Though SAPHO syndrome is rare with yet unknown
      prevalence, it still can be seen in clinical practice, and can be diagnosed by
      careful examination.

PMID- 19088843
TI  - [Research progress of dental machinable materials].
AB  - The concept of computer-aided design/computer aided manufacturing (CAD/CAM) was
      first mentioned decades ago in the field of dentistry. The technology to make
      dental restorations has found wide application recently and developed rapidly in
      prosthodontics and oral implantology, for it could save patients' time and
      manpower, have precision on prostheses' edging, etc. Until now there are several
      commercial CAD/CAM systems on market. With the use of CAD/CAM technology in
      dentistry, it has broken the traditional pattern of making dentures manually.
      Meanwhile, it brings opportunity for material science. The machinable/milled
      materials in dentistry should have not only excellent biocompatibility, but also
      machining and physical properties. Both of them are important. Nowadays, a great
      number of blocks are made from feldspar ceramics, glass-ceramics, alumina oxide,
      zirconium oxide, titanium, composite materials, wax and so on. Lots of
      researchers have had their focus on metal-free materials, because it can make the
      restorations look more natural and not show the inside metal color. However,
      strength like feldspar ceramics has its own disadvantages. It has strict
      indications, otherwise the restoration may fail. The technique called In-Ceram
      has been used long time ago. It also has long clinical experience and excellent
      long-term prognosis. People have explored this technique in CAD/CAM restorations.
      Studies have manifested that it can be utilized this way. At first, alumina was
      milled with pores; then, glass was infiltrated to the milled material. After
      zirconia had its success used in orthopedics, it became more and more popular to
      investigate whether this stuff was suitable in dentistry or not. Luckily, it has
      been proved adaptable for making single crown in posterior area, fixed partial
      dentures, in particular, and milling it using CAM equipment, due to the partially
      sintered block's hardness like chalk. Several milled polymer materials are made
      for temporary crowns or bridges. In recent years, because of the phenomenon about
      microleakage of the direct filling composite resin intraoral, indirect filling
      method, inlay, by the adhesive agent has bonded the tooth tissue and the material
      to eliminate the microleakage. It is the chemical bonding. As a result of this,
      maybe composite material made inlay will be prospective. As the aging phenomenon
      of the polymers are inevitable, and the resin matrix are polymers, it is not
      suitable for cosmetic restorations. Metal materials for CAD/CAM have some
      commercial products. But few scholars do the studies about it. In this article
      you will find that many investigators abroad do the research about the commercial
      blocks on their physical and clinical study. On the other hand, domestic scholars
      pay attention to the basis of the material research. It provides the overview of
      the materials for CAD/CAM in dentistry.

PMID- 19088844
TI  - Size variation in small-bodied humans from palau, micronesia.
AB  - BACKGROUND: Recent discoveries on Palau are claimed to represent the remains of
      small-bodied humans that may display evidence insular size reduction. This claim
      has yet to be statistically validated METHODOLOGY/PRINCIPAL FINDINGS: Published
      postcranial specimens (n = 16) from Palau were assessed relative to recent small
      bodied comparative samples. Resampling statistical approaches were employed to
      test specific hypotheses relating to body size in the Palau sample. Results
      confirm that the Palau postcranial sample is indisputably small-bodied.
      CONCLUSIONS/SIGNIFICANCE: A single, homogenous body size morph is represented in
      early prehistoric postcrania from Palau. Small body size in early Palauans is an
      ancestral characteristic and was likely not a consequence of in-situ size
      reduction. Specimens from Palau have little bearing upon hypothesised insular
      size reduction in the ancestral lineage of Homo floresiensis.

PMID- 19088845
TI  - Essential role of TGF-beta/Smad pathway on statin dependent vascular smooth
      muscle cell regulation.
AB  - BACKGROUND: The 3-hydroxy-3-methylglutaryl CoA reductase inhibitors (also called
      statins) exert proven beneficial effects on cardiovascular diseases. Recent data
      suggest a protective role for Transforming Growth Factor-beta (TGF-beta) in
      atherosclerosis by regulating the balance between inflammation and extracellular
      matrix accumulation. However, there are no studies about the effect of statins on
      TGF-beta/Smad pathway in atherosclerosis and vascular cells. METHODOLOGY: In
      cultured vascular smooth muscle cells (VSMCs) statins enhanced Smad pathway
      activation caused by TGF-beta. In addition, statins upregulated TGF-beta receptor
      type II (TRII), and increased TGF-beta synthesis and TGF-beta/Smad-dependent
      actions. In this sense, statins, through Smad activation, render VSMCs more
      susceptible to TGF-beta induced apoptosis and increased TGF-beta-mediated ECM
      production. It is well documented that high doses of statins induce apoptosis in
      cultured VSMC in the presence of serum; however the precise mechanism of this
      effect remains to be elucidated. We have found that statins-induced apoptosis was
      mediated by TGF-beta/Smad pathway. Finally, we have described that RhoA
      inhibition is a common intracellular mechanisms involved in statins effects. The
      in vivo relevance of these findings was assessed in an experimental model of
      atherosclerosis in apolipoprotein E deficient mice: Treatment with Atorvastatin
      increased Smad3 phosphorylation and TRII overexpression, associated to elevated
      ECM deposition in the VSMCs within atheroma plaques, while apoptosis was not
      detected. CONCLUSIONS: Statins enhance TGF-beta/Smad pathway, regulating ligand
      levels, receptor, main signaling pathway and cellular responses of VSMC,
      including apoptosis and ECM accumulation. Our findings show that TGF-beta/Smad
      pathway is essential for statins-dependent actions in VSMCs.

PMID- 19088846
TI  - Analysis of STAT1 activation by six FGFR3 mutants associated with skeletal
      dysplasia undermines dominant role of STAT1 in FGFR3 signaling in cartilage.
AB  - Activating mutations in FGFR3 tyrosine kinase cause several forms of human
      skeletal dysplasia. Although the mechanisms of FGFR3 action in cartilage are not
      completely understood, it is believed that the STAT1 transcription factor plays a
      central role in pathogenic FGFR3 signaling. Here, we analyzed STAT1 activation by
      the N540K, G380R, R248C, Y373C, K650M and K650E-FGFR3 mutants associated with
      skeletal dysplasias. In a cell-free kinase assay, only K650M and K650E-FGFR3
      caused activatory STAT1(Y701) phosphorylation. Similarly, in RCS chondrocytes,
      HeLa, and 293T cellular environments, only K650M and K650E-FGFR3 caused strong
      STAT1 activation. Other FGFR3 mutants caused weak (HeLa) or no activation (293T
      and RCS). This contrasted with ERK MAP kinase activation, which was strongly
      induced by all six mutants and correlated with the inhibition of proliferation in
      RCS chondrocytes. Thus the ability to activate STAT1 appears restricted to the
      K650M and K650E-FGFR3 mutants, which however account for only a small minority of
      the FGFR3-related skeletal dysplasia cases. Other pathways such as ERK should
      therefore be considered as central to pathological FGFR3 signaling in cartilage.

PMID- 19088847
TI  - Express attentional re-engagement but delayed entry into consciousness following
      invalid spatial cues in visual search.
AB  - BACKGROUND: In predictive spatial cueing studies, reaction times (RT) are shorter
      for targets appearing at cued locations (valid trials) than at other locations
      (invalid trials). An increase in the amplitude of early P1 and/or N1 event
      related potential (ERP) components is also present for items appearing at cued
      locations, reflecting early attentional sensory gain control mechanisms. However,
      it is still unknown at which stage in the processing stream these early amplitude
      effects are translated into latency effects. METHODOLOGY/PRINCIPAL FINDINGS:
      Here, we measured the latency of two ERP components, the N2pc and the sustained
      posterior contralateral negativity (SPCN), to evaluate whether visual selection
      (as indexed by the N2pc) and visual-short term memory processes (as indexed by
      the SPCN) are delayed in invalid trials compared to valid trials. The P1 was
      larger contralateral to the cued side, indicating that attention was deployed to
      the cued location prior to the target onset. Despite these early amplitude
      effects, the N2pc onset latency was unaffected by cue validity, indicating an
      express, quasi-instantaneous re-engagement of attention in invalid trials. In
      contrast, latency effects were observed for the SPCN, and these were correlated
      to the RT effect. CONCLUSIONS/SIGNIFICANCE: Results show that latency differences
      that could explain the RT cueing effects must occur after visual selection
      processes giving rise to the N2pc, but at or before transfer in visual short-term
      memory, as reflected by the SPCN, at least in discrimination tasks in which the
      target is presented concurrently with at least one distractor. Given that the
      SPCN was previously associated to conscious report, these results further show
      that entry into consciousness is delayed following invalid cues.

PMID- 19088848
TI  - The Toll-->NFkappaB signaling pathway mediates the neuropathological effects of
      the human Alzheimer's Abeta42 polypeptide in Drosophila.
AB  - Alzheimer's (AD) is a progressive neurodegenerative disease that afflicts a
      significant fraction of older individuals. Although a proteolytic product of the
      Amyloid precursor protein, the Alphabeta42 polypeptide, has been directly
      implicated in the disease, the genes and biological pathways that are deployed
      during the process of Alphabeta42 induced neurodegeneration are not well
      understood and remain controversial. To identify genes and pathways that mediated
      Alphabeta42 induced neurodegeneration we took advantage of a Drosophila model for
      AD disease in which ectopically expressed human Alphabeta42 polypeptide induces
      cell death and tissue degeneration in the compound eye. One of the genes
      identified in our genetic screen is Toll (Tl). It encodes the receptor for the
      highly conserved Tl-->NFkB innate immunity/inflammatory pathway and is a fly
      homolog of the mammalian Interleukin-1 (Ilk-1) receptor. We found that Tl loss-of
      function mutations dominantly suppress the neuropathological effects of the
      Alphabeta42 polypeptide while gain-of-function mutations that increase receptor
      activity dominantly enhance them. Furthermore, we present evidence demonstrating
      that Tl and key downstream components of the innate immunity/inflammatory pathway
      play a central role in mediating the neuropathological activities of Alphabeta42.
      We show that the deleterious effects of Alphabeta42 can be suppressed by genetic
      manipulations of the Tl-->NFkB pathway that downregulate signal transduction.
      Conversely, manipulations that upregulate signal transduction exacerbate the
      deleterious effects of Abeta42. Since postmortem studies have shown that the Ilk
      1-->NFkB innate immunity pathway is substantially upregulated in the brains of AD
      patients, the demonstration that the Tl-->NFkB signaling actively promotes the
      process of Alphabeta42 induced cell death and tissue degeneration in flies points
      to possible therapeutic targets and strategies.

PMID- 19088849
TI  - BRED: a simple and powerful tool for constructing mutant and recombinant
      bacteriophage genomes.
AB  - Advances in DNA sequencing technology have facilitated the determination of
      hundreds of complete genome sequences both for bacteria and their bacteriophages.
      Some of these bacteria have well-developed and facile genetic systems for
      constructing mutants to determine gene function, and recombineering is a
      particularly effective tool. However, generally applicable methods for
      constructing defined mutants of bacteriophages are poorly developed, in part
      because of the inability to use selectable markers such as drug resistance genes
      during viral lytic growth. Here we describe a method for simple and effective
      directed mutagenesis of bacteriophage genomes using Bacteriophage Recombineering
      of Electroporated DNA (BRED), in which a highly efficient recombineering system
      is utilized directly on electroporated phage DNA; no selection is required and
      mutants can be readily detected by PCR. We describe the use of BRED to construct
      unmarked gene deletions, in-frame internal deletions, base substitutions, precise
      gene replacements, and the addition of gene tags.

PMID- 19088850
TI  - Polymorphisms within the novel type 2 diabetes risk locus MTNR1B determine beta
      cell function.
AB  - BACKGROUND: Very recently, a novel type 2 diabetes risk gene, i.e., MTNR1B, was
      identified and reported to affect fasting glycemia. Using our thoroughly
      phenotyped cohort of subjects at an increased risk for type 2 diabetes, we
      assessed the association of common genetic variation within the MTNR1B locus with
      obesity and prediabetes traits, namely impaired insulin secretion and insulin
      resistance. METHODOLOGY/PRINCIPAL FINDINGS: We genotyped 1,578 non-diabetic
      subjects, metabolically characterized by oral glucose tolerance test, for five
      tagging single nucleotide polymorphisms (SNPs) covering 100% of common genetic
      variation (minor allele frequency > 0.05) within the MTNR1B locus (rs10830962,
      rs4753426, rs12804291, rs10830963, rs3781638). In a subgroup (N = 513), insulin
      sensitivity was assessed by hyperinsulinemic-euglycemic clamp, and in a further
      subgroup (N = 301), glucose-stimulated insulin secretion was determined by
      intravenous glucose tolerance test. After appropriate adjustment for confounding
      variables and Bonferroni correction for multiple comparisons, none of the tagging
      SNPs was reliably associated with measures of adiposity. SNPs rs10830962,
      rs4753426, and rs10830963 were significantly associated with higher fasting
      plasma glucose concentrations (p < 0.0001) and reduced OGTT- and IVGTT-induced
      insulin release (p < or = 0.0007 and p < or = 0.01, respectively). By contrast,
      SNP rs3781638 displayed significant association with lower fasting plasma glucose
      levels and increased OGTT-induced insulin release (p<0.0001 and p < or = 0.0002,
      respectively). Moreover, SNP rs3781638 revealed significant association with
      elevated fasting- and OGTT-derived insulin sensitivity (p < or = 0.0021). None of
      the MTNR1B tagging SNPs altered proinsulin-to-insulin conversion.
      CONCLUSIONS/SIGNIFICANCE: In conclusion, common genetic variation within MTNR1B
      determines glucose-stimulated insulin secretion and plasma glucose
      concentrations. Their impact on beta-cell function might represent the prevailing
      pathomechanism how MTNR1B variants increase the type 2 diabetes risk.

PMID- 19088851
TI  - Distinct determinants in HIV-1 Vif and human APOBEC3 proteins are required for
      the suppression of diverse host anti-viral proteins.
AB  - BACKGROUND: APOBEC3G (A3G) and related cytidine deaminases of the APOBEC3 family
      of proteins are potent inhibitors of many retroviruses, including HIV-1.
      Formation of infectious HIV-1 requires the suppression of multiple cytidine
      deaminases by Vif. HIV-1 Vif suppresses various APOBEC3 proteins through the
      common mechanism of recruiting the Cullin5-ElonginB-ElonginC E3 ubiquitin ligase
      to induce target protein polyubiquitination and proteasome-mediated degradation.
      The domains in Vif and various APOBEC3 proteins required for APOBEC3 recognition
      and degradation have not been fully characterized. METHODS AND FINDINGS: In the
      present study, we have demonstrated that the regions of APOBEC3F (A3F) that are
      required for its HIV-1-mediated binding and degradation are distinct from those
      reported for A3G. We found that the C-terminal cytidine deaminase domain (C-CDD)
      of A3F alone is sufficient for its interaction with HIV-1 Vif and its Vif
      mediated degradation. We also observed that the domains of HIV-1 Vif that are
      uniquely required for its functional interaction with full-length A3F are also
      required for the degradation of the C-CDD of A3F; in contrast, those Vif domains
      that are uniquely required for functional interaction with A3G are not required
      for the degradation of the C-CDD of A3F. Interestingly, the HIV-1 Vif domains
      required for the degradation of A3F are also required for the degradation of A3C
      and A3DE. On the other hand, the Vif domains uniquely required for the
      degradation of A3G are dispensable for the degradation of cytidine deaminases A3C
      and A3DE. CONCLUSIONS: Our data suggest that distinct regions of A3F and A3G are
      targeted by HIV-1 Vif molecules. However, HIV-1 Vif suppresses A3F, A3C, and A3DE
      through similar recognition determinants, which are conserved among Vif molecules
      from diverse HIV-1 strains. Mapping these determinants may be useful for the
      design of novel anti-HIV inhibitors.

PMID- 19088852
TI  - The cerebral microvasculature in schizophrenia: a laser capture microdissection
      study.
AB  - BACKGROUND: Previous studies of brain and peripheral tissues in schizophrenia
      patients have indicated impaired energy supply to the brain. A number of studies
      have also demonstrated dysfunction of the microvasculature in schizophrenia
      patients. Together these findings are consistent with a hypothesis of blood-brain
      barrier dysfunction in schizophrenia. In this study, we have investigated the
      cerebral vascular endothelium of schizophrenia patients at the level of
      transcriptomics. METHODOLOGY/PRINCIPAL FINDINGS: We used laser capture
      microdissection to isolate both microvascular endothelial cells and neurons from
      post mortem brain tissue from schizophrenia patients and healthy controls. RNA
      was isolated from these cell populations, amplified, and analysed using two
      independent microarray platforms, Affymetrix HG133plus2.0 GeneChips and CodeLink
      Whole Human Genome arrays. In the first instance, we used the dataset to compare
      the neuronal and endothelial data, in order to demonstrate that the predicted
      differences between cell types could be detected using this methodology. We then
      compared neuronal and endothelial data separately between schizophrenic subjects
      and controls. Analysis of the endothelial samples showed differences in gene
      expression between schizophrenics and controls which were reproducible in a
      second microarray platform. Functional profiling revealed that these changes were
      primarily found in genes relating to inflammatory processes.
      CONCLUSIONS/SIGNIFICANCE: This study provides preliminary evidence of molecular
      alterations of the cerebral microvasculature in schizophrenia patients,
      suggestive of a hypo-inflammatory state in this tissue type. Further
      investigation of the blood-brain barrier in schizophrenia is warranted.

PMID- 19088853
TI  - Chemoenzymatic synthesis of 4-diphosphocytidyl-2-C-methyl-D-erythritol: A
      substrate for IspE.
AB  - Enantiomerically pure 2-C-methyl-D-erythritol 4-phosphate 1 (MEP) is synthesized
      from 1,2-O-isopropylidene-alpha-D-xylofuranose via facile benzylation in good
      yield. Subsequently, 1 is used for enzymatic synthesis of 4-diphosphocytidyl-2-C
      methyl-D-erythritol 2 (CDP-ME) using 4-diphosphocytidyl-2-C-methyl-D-erythritol
      synthase (IspD). The chemoenzymatically synthesized 2 can be used as substrate
      for assay of IspE and for high throughput screening to identify IspE inhibitors.

PMID- 19088854
TI  - New Insight in Loss of Gut Barrier during Major Non-Abdominal Surgery.
AB  - BACKGROUND: Gut barrier loss has been implicated as a critical event in the
      occurrence of postoperative complications. We aimed to study the development of
      gut barrier loss in patients undergoing major non-abdominal surgery.
      METHODOLOGY/PRINCIPAL FINDINGS: Twenty consecutive children undergoing spinal
      fusion surgery were included. This kind of surgery is characterized by long
      operation time, significant blood loss, prolonged systemic hypotension, without
      directly leading to compromise of the intestines by intestinal manipulation or
      use of extracorporeal circulation. Blood was collected preoperatively, every two
      hours during surgery and 2, 4, 15 and 24 hours postoperatively. Gut mucosal
      barrier was assessed by plasma markers for enterocyte damage (I-FABP, I-BABP) and
      urinary presence of tight junction protein claudin-3. Intestinal mucosal
      perfusion was measured by gastric tonometry (P(r)CO2, P(r-a)CO2-gap). Plasma
      concentration of I-FABP, I-BABP and urinary expression of claudin-3 increased
      rapidly and significantly after the onset of surgery in most children.
      Postoperatively, all markers decreased promptly towards baseline values together
      with normalisation of MAP. Plasma levels of I-FABP, I-BABP were significantly
      negatively correlated with MAP at (1/2) hour before blood sampling (-0.726
      (p<0.001), -0.483 (P<0.001), respectively). Furthermore, circulating I-FABP
      correlated with gastric mucosal P(r)CO2, P(r-a)CO2-gap measured at the same time
      points (0.553 (p = 0.040), 0.585 (p = 0.028), respectively).
      CONCLUSIONS/SIGNIFICANCE: This study shows the development of gut barrier loss in
      children undergoing major non-abdominal surgery, which is related to preceding
      hypotension and mesenterial hypoperfusion. These data shed new light on the
      potential role of peroperative circulatory perturbation and intestinal barrier
      loss.

PMID- 19088855
TI  - An examination of morphometric variations in a neotropical toad population
      (Proceratophrys cristiceps, Amphibia, Anura, Cycloramphidae).
AB  - The species Proceratophrys cristiceps belongs to the genus Proceratophrys within
      the family Cycloramphidae. These amphibians are found exclusively in South
      America in the morphoclimatic domain of the semi-arid depression zones in
      northeastern Brazil known as the Caatinga. We examined intrapopulational
      variation using univariate and multivariate statistics with traditional and
      geometric morphometrics, which supported the existence of two morphotypes of this
      species. Our results indicated significant degrees of variation in skeletal
      characteristics between some natural populations of this species. Careful
      analyses of variability levels are fundamental to avoid taxonomic errors,
      principally in populations that demonstrate characteristics intimately associated
      with their area of occurrence, as is the case of Proceratophrys cristiceps.

PMID- 19088856
TI  - Mucin dynamics in intestinal bacterial infection.
AB  - BACKGROUND: Bacterial gastroenteritis causes morbidity and mortality in humans
      worldwide. Murine Citrobacter rodentium infection is a model for gastroenteritis
      caused by the human pathogens enteropathogenic Escherichia coli and
      enterohaemorrhagic E. coli. Mucin glycoproteins are the main component of the
      first barrier that bacteria encounter in the intestinal tract.
      METHODOLOGY/PRINCIPAL FINDINGS: Using Immunohistochemistry, we investigated
      intestinal expression of mucins (Alcian blue/PAS, Muc1, Muc2, Muc4, Muc5AC, Muc13
      and Muc3/17) in healthy and C. rodentium infected mice. The majority of the C.
      rodentium infected mice developed systemic infection and colitis in the mid and
      distal colon by day 12. C. rodentium bound to the major secreted mucin, Muc2, in
      vitro, and high numbers of bacteria were found in secreted MUC2 in infected
      animals in vivo, indicating that mucins may limit bacterial access to the
      epithelial surface. In the small intestine, caecum and proximal colon, the mucin
      expression was similar in infected and non-infected animals. In the distal
      colonic epithelium, all secreted and cell surface mucins decreased with the
      exception of the Muc1 cell surface mucin which increased after infection
      (p<0.05). Similarly, during human infection Salmonella St Paul, Campylobacter
      jejuni and Clostridium difficile induced MUC1 in the colon. CONCLUSION: Major
      changes in both the cell-surface and secreted mucins occur in response to
      intestinal infection.

PMID- 19088857
TI  - Clarifying the role of personality dispositions in risk for increased gambling
      behavior.
AB  - The current study clarifies the role of personality for increased gambling
      behaviors. The authors compared five traits, each involving a different
      disposition to rash action, predicting increased gambling behavior across the
      transition into college life. The authors sampled 418 college students (75%
      female; median age 18.0 years) across their freshman year. Participants completed
      the UPPS-P scale and measures to assess gambling and risky behavior
      participation. SEM analyses showed that although the disposition to engage in
      rash action when in an unusually positive mood (positive urgency), lack of
      planning, and sensation seeking all related to both gambling behavior and general
      risky behavior (e.g., mountain climbing) cross-sectionally, only positive urgency
      predicted longitudinal increases in gambling behavior and only sensation seeking
      predicted longitudinal increases in general risky behaviors. Beginning college
      students high in positive urgency are at increased risk to increase their
      gambling behavior in college.

PMID- 19088859
TI  - Interventions and Patterns of Risk in Adolescent HIV/AIDS Prevention.
AB  - Mid-way through the third decade of experience in preventing HIV/AIDS among
      adolescents, behavioral interventions and outcomes for high risk subgroups have
      generated evidence extremely instructive for navigating future priorities in
      reducing transmission risk behavior. Youth who abuse alcohol or drugs, who are
      detained or incarcerated, or have mental health co-morbidity such as
      externalizing disorders, represent the most significant challenge to current and
      future efforts to control the epidemic among the adolescent population. Although
      there is no unambiguous, standard intervention approach with adolescents,
      patterns of risks and outcomes with these subgroups are instructive in the
      critical priority of creating more sustainable gains with our HIV prevention
      resources. This article provides a synthesis of the evidence with these
      subgroups, discusses important limitations and difficulties in the current
      intervention science and highlights promising directions for the next generation
      of effort in reducing adolescent HIV-related sexual risk behavior. Because
      individual-level interventions have had only modest effects, a key current
      emphasis within the field is to develop multilevel interventions with a more
      ecological or contextual focus. We review various pragmatic responses that
      acknowledge this priority and the debt owed to individual-level intervention work
      with adolescents.

PMID- 19088860
TI  - Integrated Bioinformatics for Radiation-Induced Pathway Analysis from Proteomics
      and Microarray Data.
AB  - Functional analysis and interpretation of large-scale proteomics and gene
      expression data require effective use of bioinformatics tools and public
      knowledge resources coupled with expert-guided examination. An integrated
      bioinformatics approach was used to analyze cellular pathways in response to
      ionizing radiation. ATM, or ataxia-telangiectasia mutated , a serine-threonine
      protein kinase, plays critical roles in radiation responses, including cell cycle
      arrest and DNA repair. We analyzed radiation responsive pathways based on 2D
      gel/MS proteomics and microarray gene expression data from fibroblasts expressing
      wild type or mutant ATM gene. The analysis showed that metabolism was
      significantly affected by radiation in an ATM dependent manner. In particular,
      purine metabolic pathways were differentially changed in the two cell lines. The
      expression of ribonucleoside-diphosphate reductase subunit M2 (RRM2) was
      increased in ATM-wild type cells at both mRNA and protein levels, but no changes
      were detected in ATM-mutated cells. Increased expression of p53 was observed
      30min after irradiation of the ATM-wild type cells. These results suggest that
      RRM2 is a downstream target of the ATM-p53 pathway that mediates radiation
      induced DNA repair. We demonstrated that the integrated bioinformatics approach
      facilitated pathway analysis, hypothesis generation and target gene/protein
      identification.

PMID- 19088861
TI  - Electrostatics of DNA-DNA juxtapositions: consequences for type II topoisomerase
      function.
AB  - Type II topoisomerases resolve problematic DNA topologies such as knots,
      catenanes, and supercoils that arise as a consequence of DNA replication and
      recombination. Failure to remove problematic DNA topologies prohibits cell
      division and can result in cell death or genetic mutation. Such catastrophic
      consequences make topoisomerases an effective target for antibiotics and
      anticancer agents. Despite their biological and clinical importance, little is
      understood about how a topoisomerase differentiates DNA topologies in a molecule
      that is significantly larger than the topoisomerase itself. It has been proposed
      that type II topoisomerases recognize angle and curvature between two DNA helices
      characteristic of knotted and catenated DNA to account for the enzyme's
      preference to unlink instead of link DNA. Here we consider the electrostatic
      potential of DNA juxtapositions to determine the possibility of juxtapositions
      occurring through Brownian diffusion. We found that despite the large negative
      electrostatic potential formed between two juxtaposed DNA helices, a bulk
      counterion concentration as small as 50 mM provides sufficient electrostatic
      screening to prohibit significant interaction beyond an interhelical separation
      of 3 nm in both hooked and free juxtapositions. This suggests that instead of
      electrostatics, mechanical forces such as those occurring in anaphase, knots,
      catenanes, or the writhe of supercoiled DNA may be responsible for the formation
      of DNA juxtapositions.

PMID- 19088863
TI  - Potential benefits of non-pharmacological therapies in fibromyalgia.
AB  - Fibromyalgia (FM) is an incurable common syndrome of non-articular origin, and
      with no effective treatment by now. A great deal of research has sought to assess
      the efficacy of different therapies, especially non-pharmacological and low-cost
      ones, in the reduction of the intensity of symptoms. Despite the availability of
      a wide range of alternative therapies nowadays, there is little scientific
      evidence of the potential benefits of most of them, with results being
      contradictories. The purpose of this paper is to review some of the less well
      known alternative therapies in FM treatment, to describe the more relevant
      clinical studies published in this matter, and to analyze the potential effects
      of the main alternative therapies, in order to verify their efficacy.

PMID- 19088864
TI  - Improving the postmarket surveillance of total joint arthroplasty devices.
AB  - OBJECTIVE: To evaluate the FDA's approval process and postmarket surveillance
      strategies for THR devices. DESIGN: The FDA Center for Devices and Radiological
      Health (CDRH) 510k releasable database was used to document approved THR devices.
      The CDRH Medical Device Reporting data files were used to study the efficiency of
      the FDA's post-market surveillance system. Manufacturers were contacted to supply
      information regarding their implants. Medline was searched between 1966-1996 to
      determine the percentage of THR devices with published data on clinical outcomes.
      RESULTS: Between 1976 and 1996, 701 new THR devices were approved by the
      Substantial Equivalent (SE) route and 34 were approved on the basis of Premarket
      Approval PMA. The number of approvals doubled between 1991-1995 compared to 1976
      1990. Seventy-four different manufacturers obtained approval to market THR
      devices. Only four manufacturers obtained approval via the PMA application. Under
      Mandatory Device Reporting all revision arthroplasties should be reported. Using
      data from 2 independent services for which we had US hospital discharge data in
      1993 we estimate that only 3% of all revision THR were reported to the FDA.
      Manufacturers of hip implants failed to provide useful information. Medline
      search revealed only 15% of the approved THR devices had published data on
      outcomes. CONCLUSION: Current FDA premarket approval and postmarket surveillance
      strategies fail to provide information for evidence-based selection of THR
      devices. Recommendations are made to avert problems with device failures.

PMID- 19088865
TI  - Relationship between capillaroscopic alterations and bone ultrasound parameters
      in patients with raynaud phenomenon.
AB  - The aim of this study was to evaluate phalangeal bone quantitative ultrasound
      (QUS) parameters in patients with Raynaud phenomenon (RP) and relate it with
      nailfold capillaroscopy findings. Patients referring to our Rheumatology Unit
      with RP were enrolled and studied for capillaroscopy alterations; bone quality
      profile was measured by QUS of the phalanxes: AD-SoS (Amplitude Dependent Speed
      of Sound) UBPI (Ultrasound Bone Profile Index), UBI (ultrasound Bone Index), Z
      score and T score were collected. One hundred thirty six females with RP had
      investigated for age, height, weight, Body Mass Index, previous diseases and
      therapies, menopausal age were enrolled. Nailfold capillaroscopy revealed minor
      alterations (borderline capillary dilatation, no capillary loss) in 36.8% (Group
      I), major alterations (capillaries definitely dilated, avascular areas,
      microbleeding) in 37.5% (Group II) and no significative alterations in 25.7% of
      patients (Group 0). A higher frequency of low QUS parameters in phalanxes was
      observed in group II when compared to group I or 0 (72.5% vs 54% vs 18%; p<0.01).
      With an ANOVA analysis we found a significant difference between the three groups
      in terms of Ad-SOS (Group II 1750+/-140; Group I 1890+/-132; Group 0 1990+/-167,
      p<0.001), UBPI (Group II 0.21+/-0.17; Group I 0.36+/-0.21; Group 0 0.51+/-0.24,
      p<0.001), UBI (Group II 1.2+/-0.43; Group I 1.4+/-0.32; Group 0 1.5+/-0.41,
      p<0.001), Z-scores (Group II -2.8+/-1.45; Group I -1.85+/-1.27; Group 0 -1.1+/
      1.39, p<0.001) and T-scores (Group II -4.8+/-2.1; Group I -3.2+/-1.8; Group 0 
      1.8+/-2.4, p<0.001). A standard linear regression analysis revealed an
      association between the capillaroscopy findings and QUS (R 0.47+/-0.8, p<0.01).
      In our study patients with capillaroscopy alterations showed reduced phalangeal
      quantitative ultrasound parameters, more markedly in patients with scleroderma
      pattern or other major capillaroscopy alterations, independently from confounding
      variables.

PMID- 19088866
TI  - Human skin culture as an ex vivo model for assessing the fibrotic effects of
      insulin-like growth factor binding proteins.
AB  - Systemic sclerosis (SSc) is a connective tissue disease of unknown etiology. A
      hallmark of SSc is fibrosis of the skin and internal organs. We recently
      demonstrated increased expression of IGFBP-3 and IGFBP-5 in primary cultures of
      fibroblasts from the skin of patients with SSc. In vitro, IGFBP-3 and IGFBP-5
      induced a fibrotic phenotype and IGFBP-5 triggered dermal fibrosis in mice. To
      assess the ability of IGFBPs to trigger fibrosis, we used an ex vivo human skin
      organ culture model. Our findings demonstrate that IGFBP-3 and IGFBP-5, but not
      IGFBP-4, increase dermal and collagen bundle thickness in human skin explants,
      resulting in substantial dermal fibrosis and thickening. These fibrotic effects
      were sustained for at least two weeks. Our findings demonstrate that human skin
      ex vivo is an appropriate model to assess the effects of fibrosis-inducing
      factors such as IGFBPs, and for evaluating the efficacy of inhibitors/therapies
      to halt the progression of fibrosis and potentially reverse it.

PMID- 19088867
TI  - The ANKH DeltaE490Mutation in Calcium Pyrophosphate Dihydrate Crystal Deposition
      Disease (CPPDD) affects tissue non-specific Alkaline Phosphatase (TNAP)
      activities.
AB  - ANKH (human homolog of progressive ankylosis) regulates inorganic pyrophosphate
      (PPi) transport. Dominant ANKH mutations were detected in at least five multiplex
      families with calcium pyrophosphate dihydrate crystal deposition disease (CPPPD).
      The objective of this study is to assess the functional consequences of one CPPDD
      associated ANKH mutation (DeltaE490) in chondrogenic ATDC5 cells. Stable ATDC5
      transfectants bearing myc-tagged constructs of wild-type ANKH, mutant ANKH
      (DeltaE490) and neo controls were generated. Upon ITS (insulin, transferrin and
      selenium) induction, expression of chondrocyte markers including alkaline
      phosphatase activity in the various transfectants was assessed. The ANKH
      DeltaE490- transfectants had low alkaline phosphatase activities throughout ITS
      treatment due to lower TNAP protein expression and the presence of intracellular
      low-molecular-weight inhibitors. Our results suggest that the interplay of ANKH
      and TNAP activities is tightly regulated.

PMID- 19088868
TI  - Successful treatment of frozen hip with manipulation and pressure dilatation.
AB  - A 44-year old man with prolonged frozen hip was treated with manipulation under
      anesthesia and pressure dilatation of the left hip joint. The treatment was
      successful and after one year the hip was symptomless.

PMID- 19088869
TI  - Cigarette smoking, birthweight and osteoporosis in adulthood: results from the
      hertfordshire cohort study.
AB  - We looked for interaction between early environment and adult lifestyle in
      determination of bone mineral content (BMC) and bone mineral density (BMD) among
      498 men and 468 women for whom birth records were available. Participants
      completed a health questionnaire, and bone densitometry (DXA) of the lumbar spine
      and femoral neck performed.We found no relationships between cigarette and
      alcohol consumption, physical activity and either BMC or BMD after adjustment for
      age, body mass index, dietary calcium, social class, HRT use and years since
      menopause. However, male current smokers in the lowest third of birth weight had
      lower femoral neck BMD than ex- or never smokers from the lowest birth weight
      third (p value for interaction term = 0.04). Similar trends were seen with
      femoral neck BMC and lumber spine BMC.Individuals of lower birth weight may be
      particularly vulnerable to the effects of bone noxious stimuli such as cigarette
      smoking.

PMID- 19088870
TI  - Resistance to rituximab therapy and local BAFF overexpression in Sjogren's
      syndrome-related myoepithelial sialadenitis and low-grade parotid B-cell
      lymphoma.
AB  - OBJECTIVE: B-cell expansion is a key feature of Sjogren's syndrome (SS).
      Accordingly, several studies have reported the benefits of B-cell depletion with
      anti-CD20 monoclonal antibody (Rituximab) in the treatment of glandular and
      extraglandular manifestations of SS. Patients with SS are at increased risk of
      lymphoma development. B-lymphocyte stimulator (BAFF) is an essential cytokine for
      the control of B-cell maturation and survival, and high levels of BAFF were
      described in the serum and salivary glands of SS patients, strongly suggesting a
      crucial role in the proliferation of B cells in SS. PATIENT AND METHODS: We
      describe the treatments employed, with particular regards to rituximab therapy,
      and the histopathologic and biologic studies, in particular BAFF levels in serum
      and in pathologic tissues before and after B-cell depletion therapy, and the
      characterization of the cultured epithelial cells obtained by the parotid gland
      MALT-lymphoma, in a case of a 51-year old woman with primary SS and mixed
      cryoglobulinaemia type II with features of systemic vasculitis, who developed a
      bilateral parotid MALT-type lymphoma. Rheumatoid factor (RF), cryoglobulins, BAFF
      levels were assessed monthly up to month +6, then at the end of follow-up (month
      +12), as well as peripheral blood CD19-positive B-cell level RESULTS: A
      significant systemic effect of rituximab on B-cell biomarkers was documented,
      however, the cryoglobulinemic syndrome did not improve and the parotid
      enlargement did not decrease confirming the failure of B-cell depletion to affect
      the parotid lymphoma. BAFF levels decreased only under B-cell depletion
      associated with high-dose steroids. Tissue studies further documented the
      persistent overexpression of BAFF in the salivary gland pathologic tissue during
      the disease course. CONCLUSION: Tissue and systemic overexpression of BAFF may
      have contributed to resistance to rituximab therapy, in MALT lymphoproliferation
      associated with SS. Thus, alternative treatment strategies should be then
      considered, possibly including BAFF-targeted approaches.

PMID- 19088871
TI  - Work disability in scleroderma is greater than in rheumatoid arthritis and is
      predicted by high HAQ scores.
AB  - OBJECTIVES: To estimate the frequency of work disability (WD) in a cohort of
      patients with Systemic Sclerosis (SSc) vs an internal control group of patients
      with rheumatoid arthritis (RA) with a known high frequency of WD; and to
      investigate the association between WD and other factors including Health
      Assessment Questionnaire Disability Index (HAQ-DI) scores, HAQ pain, age, sex,
      disease duration and education level. METHODS: Cross-sectional data on WD status
      were obtained from a questionnaire sent to all SSc (n = 35 limited [lcSSc], 26
      diffuse [dcSSc]) and a subset of RA patients (n=104) from a rheumatology
      practice. WD data, HAQ-DI scores, and demographic/clinical features (age, sex,
      high school education, disease duration and SSc disease subtype [dcSSc vs lcSSc])
      were recorded. RESULTS: The proportion with WD was 0.56 in SSc (95% CI: 0.43
      0.68) vs 0.35 in RA (95% CI: 0.25-0.44), p= 0.009. HAQ-DI scores were
      significantly higher in work-disabled SSc and RA patients vs those who were
      employed (p=0.0001, and p <0.0001). Multivariate logistic regression analysis
      demonstrated that higher HAQ-DI scores (beta=1.78, p <0.001), disease type
      (dcSSc, lcSSc, RA) (beta=1.32 for dcSSc, p=0.032), and self-reported disease
      duration (beta=0.04, p=0.042) were significantly associated with WD (R(2)=0.311).
      Adding a work-related factor (self-reported physically demanding work) improved
      the regression model (R(2)=0.346) and strengthened the HAQ-DI (beta=1.86, p
      <0.001) and lcSSc (beta=1.24, p=0.024) coefficients. CONCLUSION: The frequency of
      WD in SSc was high and was greater than in RA. SSc (and dcSSc) had significantly
      more WD than RA. The HAQ-DI was strongly associated with WD in SSc.

PMID- 19088872
TI  - The changing face of spondyloarthropathies under TNF alpha blockade.
AB  - OBJECTIVES: Tumor necrosis factor alpha (TNF-alpha ) therapy has been implicated
      in the development of autoimmune diseases. Our aim was to describe three patients
      with spondyloarthropathies who responded to infliximab, a chimeric monoclonal
      antibody specific for TNF-alpha but developed new symptoms of
      spondyloarthropathies. In parallel, a review of the literature on psoriasis
      induced by TNF-alpha blockers was undertaken. RESULTS: The first patient had been
      suffering from ankylosing spondylitis (AS) for more than 12 years. Infliximab
      induced a remission of AS, but he developed overt Crohn's disease two years after
      starting treatment. The second patient had AS for more than 20 years. Infliximab
      had an excellent effect on his AS, but he developed palmo-plantar psoriasis a few
      months after initiating therapy with the drug. The third patient, whose long-term
      and severe psoriasis had responded to infliximab developed peripheral arthritis.
      A review of the literature revealed 63 cases of psoriasis induced by TNF-alpha
      blockers (33 on Infliximab, 16 on Etanercept and 14 on Adalimumab). The
      underlying diseases were variable, including all the spectrum of conditions for
      which TNF-alpha blockers are indicated. Patients developed psoriasis after a mean
      duration of treatment of 11 months. Interstingly, a substantial proportion of
      patients continued treatment with TNF alpha blockers, the psoriasis improving in
      a majorityof cases under topical treatment only. CONCLUSION: While Infliximab may
      change the course of spondyloarthropathy, depressing the original symptoms it may
      uncover other occult aspects of these diseases.

PMID- 19088873
TI  - Risk factors for osteoporosis and fractures in postmenopausal women between 50
      and 65 years of age in a primary care setting in Spain: a questionnaire.
AB  - INTRODUCTION: Osteoporosis (OP) is a major, highly prevalent health problem and
      osteoporosis-related fractures account for high morbidity and mortality.
      Therefore, prevention and early detection of osteoporosis should strive to
      substantially reduce this risk of fracture. OBJECTIVE: The present observational,
      descriptive, cross-sectional study sought to assess the prevalence of risk
      factors for osteoporosis and fractures in a large sample of postmenopausal women
      aged 50 to 65 years attending Primary Care facilities in Spain. METHODS: We
      recruited 4,960 women, at 96 Primary Care centers. Demographic and
      anthropometrical data, as well as information regarding risk factors for OP were
      collected using a questionnaire. RESULTS: the prevalence rates for the major
      osteoporosis risk factors in our population were: low calcium intake, 43%;
      benzodiazepine use, 35.1%, and height loss, 30.1%. Other relatively prevalent
      factors include: having suffered at least one fall during the preceding year;
      positive family history of falls (particularly on the mother's side), smoking,
      kyphosis, presence of any disease affecting bone metabolism, personal history of
      falls, and inability to rise from a chair without using one's arms. The least
      frequent factors were weight loss of greater than 10% over the preceding 10 years
      and problems in sensory perception that affect patient's ability to walk.
      CONCLUSIONS: The main risk factors for osteoporosis in women 50-65 years of age
      are low calcium intake, use of benzodiazepines, and observed loss of height. Our
      results may help physicians to identify groups at risk for OP and fractures at
      early stages and consequently, optimize prevention and early diagnosis of
      osteoporosis in postmenopausal women.

PMID- 19088874
TI  - Determining a relationship between applied occlusal load and articulating paper
      mark area.
AB  - Articulating paper mark size has been widely accepted in the dental community to
      be descriptive of occlusal load. The objective of this study is to determine if
      any direct relationship exists between articulating paper mark area and applied
      occlusal load. A uniaxial testing machine repeatedly applied a compressive load,
      beginning at 25N and incrementally continuing up to 450N, to a pair of epoxy
      dental casts with articulating paper interposed. The resultant paper markings (n
      = 600) were photographed, and analyzed the mark area using a photographic image
      analysis and sketching program. A two-tailed Student's t-test for unequal
      variances compared the measured size of the mark area between twelve different
      teeth (p < 0.05). Graphical interpretation of the data indicated that the mark
      area increased non-linearly with increasing load. When the data was grouped to
      compare consistency of the mark area between teeth, a high variability of mark
      area was observed between different teeth at the same applied load. The Student's
      t-test found significant differences in the size of the mark area approximately
      80% of the time. No direct relationship between paper mark area and applied load
      could be found, although the trend showed increasing mark area with elevating
      load. When selecting teeth to adjust, an operator should not assume the size of
      paper markings, accurately describing the markings' occlusal contact force
      content.

PMID- 19088875
TI  - Whole Saliva has a Dual Role on the Adherence of Candida albicans to
      Polymethylmetacrylate.
AB  - Adhesion of Candida albicans to acrylic of dental prostheses or to salivary
      macromolecules adsorbed on their surface is believed to be a critical event in
      the development of denture stomatitis. In previous studies our group has shown
      that adhesion of C. albicans germ tubes to polystyrene is decreased by saliva
      whereas C. albicans yeast cells adhesion to the same material is enhanced. The
      results presented in this study confirm this dual role played by whole saliva,
      since it decreased the adhesion of germ tubes but increased the adhesion of yeast
      cells to polymethylmetacrylate (PMMA). These effects mediated by whole saliva do
      not seem to be related to an inhibition of the germination of C. albicans, since
      similar levels of filamentation were observed in presence and absence of saliva.
      These results may give new insights into the conflicting role of saliva in the
      adhesion of C. albicans to acrylic resins of dental prostheses.

PMID- 19088876
TI  - A role for non-antimicrobial actions of tetracyclines in combating oxidative
      stress in periodontal and metabolic diseases: a literature review.
AB  - This review addresses the role of adjunctive tetracycline therapy in the
      management of periodontal diseases and its efficacy in reducing inflammatory
      burden, oxidative stress and its sequelae in patients with coexisting features of
      metabolic syndrome. Removal of the dimethylamine group at C4 of the tetracycline
      molecule reduces its antibiotic properties, enhancing its non-antimicrobial
      actions; this strategy has aided the development of several chemically modified
      tetracyclines such as minocycline and doxycycline, by altering different regions
      of the molecule for focused action on biological targets. Tetracyclines are
      effective in reducing inflammation by inhibiting matrix metalloproteinases,
      preventing excessive angiogenesis, inhibiting apoptosis and stimulating bone
      formation. There are important applications for tetracyclines in the management
      of diabetic, dyslipidaemic periodontal patients who smoke. The diverse mechanisms
      of action of tetracyclines in overcoming oxidative stress and enhancing matrix
      synthesis are discussed in this review.

PMID- 19088877
TI  - Effect of the simulated disinfection by microwave energy on the impact strength
      of the tooth/acrylic resin adhesion.
AB  - The objective of this study was to determine the effect of simulated microwave
      disinfection on the tooth/acrylic resin impact strength. Acrylic molar teeth with
      a wax stick attached to the ridge lap were included in brass flasks. Specimens
      were made with Classico thermopolymerized acrylic resin, according to the groups:
      1 and 5 - tooth with no treatment (control); 2 and 6 - tooth bur abrasion; 3 and
      7 - tooth bur retention; and 4 and 8 - tooth monomer etch. Eighty specimens
      (n=10) were polymerized in bath cycle at 74( masculine)C for 9 hours and
      deflasked after flask cooling. Specimen from groups 2, 4, 6 and 8 was submitted
      to simulated microwave disinfection in a microwave oven at 650W for 3 minutes.
      Impact strength test was performed with an Otto Wolpert-Werke machine (Charpy
      system) with an impact load of 40 kpcm. Fracture load value was transformed into
      impact strength as a function of the bond area (kfg/cm(2)). Collected data were
      submitted to ANOVA and Tukey's test (alpha=.05) and results indicate that the
      simulated microwave disinfection decreased the impact strength in all treatments.

PMID- 19088878
TI  - The Antimicrobial Effect of Silver Ion Impregnation into Endodontic Sealer
      against Streptococcus mutans.
AB  - Pulpal and periradicular diseases are primarily caused by bacterial invasion of
      the root canal system as a result of caries progression. The presence of residual
      bacteria at the time of root canal completion (obturation) is associated with
      significantly higher rate of treatment failure. Re-infection of obturated root
      canals can be potentially prevented by enhancing the antibacterial activities of
      root canal obturation materials. We evaluated, in an in vitro model, the
      antimicrobial efficacy of silver ions added to a common endodontic sealer. For
      that purpose we performed growth inhibition studies and bacterial viability
      tests. We measured the zone of inhibition, optical density and performed confocal
      laser scanning microscopy. Our results show that the silver ions enhance the
      antimicrobial activity of the root canal sealer against Streptococcus mutans.
      This study approach may hold promise for studying other biologically based
      therapies and therefore increasing the success rate of routine orthograde root
      canal treatment.

PMID- 19088879
TI  - Predictive Role of p53 Protein as a Single Marker or Associated to Ki67 Antigen
      in Oral Carcinogenesis.
AB  - p53 over-expression has been proposed as a reliable marker associated to oral
      carcinogenesis, although only about 50% of oral carcinomas (OSCC) are associated
      with p53 over-expression and even p53-negative lesions can progress to OSCC. The
      aim of the study was to determine whether the combination of p53 over-expression
      and p53 low-expression associated with Ki67 over-expression (high Ki67/p53 ratio)
      could lead to a more sensitive parameter. Immunohistochemical expression of Ki67
      and p53 was measured in 54 specimens from OSCC; 27 specimens from moderate/severe
      epithelial dysplasia; 32 specimens from oral leukoplakias without epithelial
      dysplasia, and 13 specimens with normal epithelium. p53 over-expression was found
      in 31 (53%) samples from OSCC, in 10 (37%) samples from severe dysplasias, and in
      5 (15%) samples from non-dysplastic lesions, while the combination of high p53
      values with high Ki67/p53 ratio was observed in 93% of OSCC, in 81% of dysplastic
      lesions, and in 50% of non-dysplastic lesions. This parameter may have a clinical
      implication to detect early lesions with an impairment of p53 pathway, and
      probably at risk of progress to OSCC.

PMID- 19088880
TI  - Assessing double Acid-etched implants submitted to orthodontic forces and used as
      prosthetic anchorages in partially edentulous patients.
AB  - The use of implants as anchorage for orthodontic forces seems to be a good
      alternative in partially edentulous patients needing orthodontic treatment. This
      study is aimed at assessing the performance and behavior of microtextured surface
      endosseous implants obtained by means of a double acid etching against
      orthodontic forces, as well as their adequacy to be used first as anchorage and
      later as fixtures for the definitive prosthesis. MATERIALS AND METHODS: A total
      of 93 double acid-etched surface parallel wall implants (Osseotite(R) Implants,
      Implant Innovations Inc., Palm Beach, Florida, USA) were inserted in 38 partially
      edentulous patients prior to orthodontic treatment This was carried out by
      following two-stage surgery protocols in the maxilla as well as in the mandible.
      After a healing period of six months for the maxilla and four months for the
      mandible, the implants were used as anchorage for sliding, compression and
      traction orthodontic forces between 100 to 200 g by means of Ni-TI springs. Bone
      level and Resonance Frequency Analysis (RFA) were measured before and after the
      introduction of the orthodontics forces. RESULTS: After removal of the
      orthodontics appliances, all the implants remained stabile and served as support
      for prosthetic replacement of missing teeth. The bone level showed no
      variationeven when a positive difference 0.02 +/- 0.38mm was noticed. The RFA
      scored a significant difference (p</= 0.03) between the initial Implant Stability
      Quotient (ISQ) values (66) and the final ones (68). CONCLUSIONS: These findings
      showed that Osseotite implants were able to support the orthodontic forces
      applied during this investigation, maintaining osseointegration without
      significant variation in bone level. Therefore, they can be used to support
      dental prosthesis once they have been used as orthodontic anchorage under the
      cited conditions.

PMID- 19088881
TI  - Treatment in Borderline Class III Malocclusion: Orthodontic Camouflage
      (Extraction) Versus Orthognathic Surgery.
AB  - AIMS: To investigate the differences in morphological characteristics of
      borderline class III patients who had undergone camouflage orthodontic treatment
      or orthognathic surgery, and to compare the treatment effects between these two
      modalities. MATERIALS AND METHODS: Cephalograms of 25 patients (13 orthodontic,
      12 surgical) with class III malocclusion were analyzed. All had a pretreatment
      ANB angle greater than -5 masculine. RESULTS: Using discriminant analysis, only
      Holdaway angle was selected to differentiate patients in the pretreatment stage.
      Seventy-two per cent patients were correctly classified. In the orthodontic
      group, reverse overjet was corrected by retraction of the lower incisors and
      downward and backward rotation of the mandible. The surgical group was corrected
      by setback of the lower anterior dentoalveolus and uprighting of the lower
      incisors. No difference was found in posttreatment soft tissue measurements
      between the two groups. CONCLUSIONS: Twelve degree for the Holdaway angle can be
      a guideline in determining the treatment modalities for borderline class III
      patients, but the preferences of operators and patients are also important. (2)
      Both therapeutic options should highlight changes in the lower dentoalveolus and
      lower incisors. (3) Both treatment modalities can achieve satisfactory
      improvements to the people.

PMID- 19088883
TI  - Influence of finishing/polishing procedures on the surface texture of two resin
      composites.
AB  - This study compared surface roughness and gloss produced by different
      finishing/polishing procedures for two resin composites, Clearfil AP-X (AP-X) and
      Estelite Sigma (ES). A total of 70 composite discs (n=35 for each resin
      composite) were prepared and divided at random into seven finishing/polishing
      groups (n=5): glass-pressed control; using a super-fine-grit diamond bur (SF);
      using CompoMaster (CM) after SF-finishing (SF+CM); using White Point (WP) after
      SF-finishing (SF+WP); using CM after SF+WP-finishing (SF+WP+CM); using
      Stainbuster (SB) after SF-finishing (SF+SB); and using CM after SF+SB-finishing
      (SF+SB+CM). After the finishing/polishing procedures, average surface roughness
      (R(a)) and surface gloss (Gs(60( degrees ))) of all specimens were assessed with
      a surface profilometer and specimen gloss meter, respectively. Glass-pressed
      controls for both AP-X and ES composites showed the best surface finish in terms
      of both R(a) and Gs(60( degrees )). SF-finishing produced the roughest surface
      and led to almost complete loss of gloss. While additional polishing with CM
      reduced R(a) and increased Gs(60( degrees )), the additional finishing effect of
      WP or SB between SF-finishing and CM-polishing was not found for either AP-X or
      ES.

PMID- 19088882
TI  - Optimizing qPCR for the Quantification of Periodontal Pathogens in a Complex
      Plaque Biofilm.
AB  - Quantitative PCR (qPCR) has recently been used to quantify microorganisms in
      complex communities, including dental plaque biofilms. However, there is
      variability in the qPCR protocols being used. This study was designed to evaluate
      the validity of two of these variables with the intent of developing a more
      standardized qPCR protocol. The two variables evaluated were (1) the use of DNA
      content versus actual cell counts to estimate bacterial numbers in mixed plaque
      samples and (2) the effectiveness of three different universal primers versus
      species specific primers in amplifying specific target pathogens in these
      samples. Results lead to the development of a standardized protocol that was
      shown to be highly reproducible as demonstrated by low coefficients of variation.
      The results also confirmed that this standardized qPCR protocol can be used as a
      sensitive method for quantifying specific bacterial species in human plaque
      samples.

PMID- 19088884
TI  - Effect of repeated simulated disinfections by microwave energy on the complete
      denture base adaptation.
AB  - This study evaluated the effect of repeated microwave disinfections on the
      adaptation of the maxillar denture base using 2 different flask closure methods.
      Twenty stone cast-wax base sets were prepared for flasking by traditional cramp
      or RS system methods. Five bases for each method were submitted to 5 repeated
      simulated disinfections in a microwave oven with 650W for 3 minutes. Control
      bases were not disinfected. Three transverse cuts were made through each stone
      cast-resin base set, corresponding to canine, first molar, and posterior region.
      Measurements were made using an optical micrometer at 5 points for each cut to
      determine base adaptation: left and right marginal limits of the flanges, left
      and right ridge crests, and midline. Results for base adaptation performed by the
      flask closure methods were: traditional cramp (non-disinfected = 0.21 +/- 0.05mm
      and disinfected = 0.22 +/- 0.05mm), and RS system (non-disinfected = 0.16 +/-
      0.05 and disinfected = 0.17 +/- 0.04mm). Collected data were submitted to ANOVA
      and Tukey test (alpha=.05). Repeated simulated disinfections by microwave energy
      did not cause deleterious effect on the base adaptation, when the traditional
      cramp and RS system flask closure methods were compared.

PMID- 19088885
TI  - An In vivo Model for Short-Term Evaluation of the Implantation Effects of
      Biomolecules or Stem Cells in the Dental Pulp.
AB  - The continuously growing rodent incisor is a widely used model to investigate
      odontogenesis and mineralized tissue formation. This study focused on evaluating
      the mouse mandibular incisor as an experimental biological tool for analyzing in
      vivo the capacity of odontoblast-like progenitors or bioactive molecules to
      contribute to reparative dentinogenesis. We describe here a surgical procedure
      allowing direct access to the forming part of the incisor dental pulp Amelogenin
      peptide A+4 adsorbed on agarose beads, or dental pulp progenitor cells were
      implanted in the pulp following this procedure. After 10 days A+4 induced the
      formation of an osteodentin occluding almost the totality of the pulp
      compartment. Implantation of progenitor cells leads to formation of islets of
      osteodentin-like structures located centrally in the pulp. These pilot studies
      validate the incisor as an experimental model to test the capacity of progenitor
      cells or bioactive molecules to induce the formation of reparative dentin.

PMID- 19088887
TI  - Carbonyl Reductase 3 (CBR3) Mediates 9-cis-Retinoic Acid-Induced Cytostatis and
      is a Potential Prognostic Marker for Oral Malignancy.
AB  - The molecular mechanisms of growth suppression by retinoic acid (RA) were
      examined. Our results suggest that the cytostatic effects of RA could be mediated
      by the activation of endogenous CBR3 gene in oral squamous cell carcinomas
      (OSCCs), and the expression is a potential marker for oral malignancy.

PMID- 19088886
TI  - Clinical Practice: Giant Cell Tumour of the Jaw Mimicking Bone Malignancy on
      Three-Dimensional Computed Tomography (3D CT) Reconstruction.
AB  - A wide range of diseases may present with radiographic features of osteolysis.
      Periapical inflammation, cysts and benign tumours, bone malignancies, all of
      these conditions may show bone resorption on radiograph. Features of the
      surrounding bone, margins of the lesion, and biological behaviour including
      tendency to infiltration and root resorption, may represent important criteria
      for distinguishing benign tumours from their malign counterpart, although the
      radiographic aspect of the lesion is not always predictive. Therefore a critical
      differential diagnosis has to be reached to choose the best management. Here, we
      report a case of giant cell tumour (GCT) whose radiological features by computed
      tomography (CT) suggested the presence of bone malignancy, whereas the evaluation
      of a routine OPT scan comforted us about the benign nature of the lesion. A brief
      review of the literature on such a benign but locally aggressive neoplasm is also
      provided.

PMID- 19088888
TI  - Effect of age on flow-rate, protein and electrolyte composition of stimulated
      whole saliva in healthy, non-smoking women.
AB  - As relatively little is known about the effect of age on salivary electrolytes we
      studied the composition of saliva as function of age to provide reference values
      for healthy non-smoking women. All non-medicated and non-smoking 30-59-year-old
      subjects (n=255) selected from among 1030 women participating in a screening
      program formed the material of the present study. Salivary calcium, inorganic
      phosphate, magnesium, sodium, potassium, protein and flow-rate of stimulated
      whole saliva were measured. We found age-related changes in salivary calcium and
      phosphate concentrations (p=0.001 and p=0.004, respectively, one-way ANOVA). Peak
      values occurred at around 50-54 years of age. Age had no effect on flow-rate,
      magnesium, sodium, potassium or proteins. The concentration of sodium correlated
      positively, while phosphate, potassium, magnesium and protein correlated
      negatively with the salivary flow-rate. Calcium was the only electrolyte which
      had no association with flow-rate. Our study provides reference values for
      salivary electrolytes of 30-59-year-old women.

PMID- 19088889
TI  - Direct restorative treatment of missing maxillary laterals with composite
      laminate veneer: a case report.
AB  - This clinical report describes a direct composite laminate veneer restoration of
      the maxillary anterior teeth in one chair time to produce a better esthetic
      appearance in a patient with diastemata and missing laterals.

PMID- 19088891
TI  - Effect of bilateral mandibular osteodistration on the condylar cartilage: an
      experimental study on rabbits.
AB  - Although various aspects of bone formation during distraction osteogenesis have
      been studied extensively, there are only limited experimental data concerning the
      influence of hyper-physiologic mandibular distraction rate on structural
      alterations in the temporomandibular joint (TMJ) condylar cartilage. The purpose
      of this study was to evaluate the effect of bilateral distraction osteogenesis of
      the mandibular body, at a hyper-physiologic rate and length, on the integrity of
      the condylar cartilage in rabbits. MATERIALS AND METHODS: Eighteen healthy adult
      male rabbits weighing 2 to 3 kg were assigned to 1 of 2 groups: the control group
      (n = 2 rabbits, 4 joints) or the study group (n = 16 rabbits, 32 joints) four
      rabbits (8 joints) in each subgroup according to the post-distraction period
      (1,2,3 or 4 weeks). In the control group, rabbits received sham surgery
      (Osteotomy without distraction) and then left to live for 4 weeks under the same
      condition of the study group then euthanized using intravenous overdose of
      pentobarbital sodium. In the study group, an extra oral custom-made distracter
      was employed to achieve bilateral mandibular hyper physiologic distraction (1.5
      mm twice daily for 5 days) distraction. All animals were evaluated clinically and
      histomorphometrically and results analyzed by MINITABE 13.1 statistical package
      using ANOVA test. RESULTS: Animals underwent distraction showed obvious changes
      in condylar surface contour related to length of the follow up period, compared
      to the control; these changes seemed to be partly reversible. The most pronounced
      observation was the irregularities and resorption in the anterior part of the
      condylar cartilage and the subcondylar bone. Moreover, at the first two weeks,
      the area of resorption was invaded by large number of osteoclasts and chronic
      inflammatory cells which declined later in the 3rd and 4th weeks and replaced
      with osteoblastic activities. CONCLUSION: These experimental data showed that
      distraction rate of 3 mm per day may lead to degenerative or even early arthritic
      changes in the TMJ condylar cartilage in the 1st and 2nd post-distraction weeks.
      However, all condyles showed adaptive and remodeling sings in the following 3rd
      and 4th weeks.

PMID- 19088890
TI  - Proteolytic Activities of Oral Bacteria on ProMMP-9 and the Effect of Synthetic
      Proteinase Inhibitors.
AB  - Tissue reactions to bacteria lead to proinflammatory reactions involving matrix
      metalloproteinases (MMPs). Synthetic protease inhibitors may offer new
      possibilities to regulate bacterial proteases. We investigated proteolytic
      activities of certain periodontal bacteria, their effects on the latent proMMP-9,
      and the effects of synthetic MMP inhibitors and a serine protease inhibitor
      Pefabloc. The strains studied were Porphyromonas gingivalis, Prevotella
      intermedia, Peptostreptoccus micros, Prevotella nigrescens, Fusobacterium
      nucleatum, and 5 Aggregatibacter actinomycetemcomitans serotypes. Their
      gelatinolytic activities and the effects of certain synthetic MMP inhibitors and
      Pefabloc were analyzed by zymography. Bacterial effects on proMMP-9 conversion
      were investigated by Western immunoblot. All investigated periodontal bacteria
      produced gelatinolytic cell-bound and extracellular proteinases which could
      fragment latent proMMP-9, suggesting co-operative processing cascades in oral
      tissue remodeling. A. actinomycetemcomitans produced the weakest gelatinolytic
      activity. Synthetic proteinase inhibitors exhibited slight but clear reductive
      effects on the bacterial proteolytic activities. We conclude that targeted anti
      proteolytic treatment modalities against bacterial-host proteolytic cascades can
      be developed.

PMID- 19088892
TI  - Bond strength of gold alloys laser welded to cobalt-chromium alloy.
AB  - The objective of this study was to investigate the joint properties between cast
      gold alloys and Co-Cr alloy laser-welded by Nd:YAG laser. Cast plates were
      fabricated from three types of gold alloys (Type IV, Type II and low-gold) and a
      Co-Cr alloy. Each gold alloy was laser-welded to Co-Cr using a dental laser
      welding machine. Homogeneously-welded and non-welded control specimens were also
      prepared. Tensile testing was conducted and data were statistically analyzed
      using ANOVA. The homogeneously-welded groups showed inferior fracture load
      compared to corresponding control groups, except for Co-Cr. In the specimens
      welded heterogeneously to Co-Cr, Type IV was the greatest, followed by low-gold
      and Type II. There was no statistical difference (P<0.05) in fracture load
      between Type II control and that welded to Co-Cr. Higher elongations were
      obtained for Type II in all conditions, whereas the lowest elongation occurred
      for low-gold welded to Co-Cr. This study indicated that, of the three gold alloys
      tested, the Type IV gold alloy was the most suitable alloy for laser-welding to
      Co-Cr.

PMID- 19088893
TI  - Rituximab for refractory rheumatoid arthritis: a 24-week open-label prospective
      study.
AB  - OBJECTIVES: To study the efficacy of rituximab in active rheumatoid arthritis
      (RA) patients refractory to disease modifying anti-rheumatic drugs (DMARDs)
      including the tumor necrosis factor (TNF)-alpha antagonists. METHODS: Adult
      patients with active RA despite adequate therapies with conventional DMARDs or
      anti-TNFalpha agents for at least 3 months were recruited. Inclusion criteria
      were: (1) Positive RF / anti-CCP; (2) >/= 6 swollen joints and >/= 8 tender
      joints; (3) ESR >/= 28 mm/hr or CRP >/= 10 mg/L. Eligible patients were given
      intravenous rituximab infusions at a dose of 1000 mg on days 1 and 15. Assessment
      was performed 4-weekly thereafter and included tender joint counts (TJC), swollen
      joint counts (SJC), physician's and patient's global assessment, patient's pain
      assessment (VAS 0-100 mm), disability index (HAQ-DI), quality of life (SF36),
      fatigue score (FACIT-F), ESR and CRP. The DAS28, EULAR and ACR responses at week
      24 were evaluated. RESULTS: 10 patients (8 women and 2 men) were studied (mean
      age: 49 years; mean RA duration 7.4 years). Baseline TJC and SJC were 25.1 +/-
      13.2 and 12.8 +/- 5.4 respectively. The mean DAS28 score was 7.1 +/- 0.7, and the
      mean CRP and ESR levels were 52.3 +/- 60 mg/L and 95.8 +/- 32 mm/hr,
      respectively. The median number of failed DMARDs was 4 and two patients had
      failed anti-TNFalpha treatment. At week 24, there was a significant drop in TJC,
      SJC, ESR and CRP. The HAQ-DI score also decreased from 2.1 to 1.7 (p=0.04) while
      the total SF-36 score improved from 24.8 to 38.3 (p=0.008). Sixty percent of
      patients achieved EULAR moderate-to-good response. Half of the patients achieved
      ACR20 and two achieved ACR50 / 70 response. Only one patient experienced a minor
      infusion reaction. CONCLUSIONS: Rituximab is effective and well tolerated in
      patients with refractory RA.

PMID- 19088894
TI  - Complementary and alternative medicine use in musculoskeletal disorders: does
      medical skepticism matter?
AB  - Medical skepticism is the reservation about the ability of conventional medical
      care to significantly improve health. Individuals with musculoskeletal disorders
      seeing specialists usually experience higher levels of disability; therefore it
      is expected they might be more skeptical of current treatment and thus more
      likely to try Complementary and Alternative Medicine (CAM). The goal of this
      study was to define these relationships. These data were drawn from a cross
      sectional survey from two cohorts: those seeing specialists (n=1,344) and non
      specialists (n=724). Site-level fixed effects logistic regression models were
      used to test associations between medical skepticism and 10 CAM use categories.
      Some form of CAM was used by 88% of the sample. Increased skepticism was
      associated with one CAM category for the non-specialist group and six categories
      for the specialist group. Increased medical skepticism is associated with CAM
      use, but medical skepticism is more often associated with CAM use for those
      seeing specialists.

PMID- 19088895
TI  - Infections are not increased in scleroderma compared to non-inflammatory
      musculoskeletal disorders prior to disease onset.
AB  - The etiology of scleroderma (SSc) is unknown; immunogenic stimuli such as
      infections and vaccinations could theoretically be risk factors for scleroderma.
      Our objective was to assess the relationship between viral and bacterial
      infections, and vaccinations, prior to diagnosis of SSc compared to non
      inflammatory controls. METHODS: A questionnaire was sent to individuals with SSc
      (n =83) and controls (n=351) with non-inflammatory musculoskeletal (MSK)
      disorders (osteoarthritis, n = 204; tendonitis, n = 58; fibromyalgia, n= 89) from
      a rheumatology practice. Questions ascertained past infections, exposure to
      infectious agents and vaccination history. RESULTS: The response rate was 78%
      (SSc) and 56% (MSK controls). The mean age was 56 +/- 1.6 (SSc) and 58 +/- 0.9
      (MSK); 88% (SSc) and 82% (MSK) were female. No association between prior
      infections and SSc was observed. In fact, controls were more likely than SSc
      subjects to report any infection within 1-year prior to disease diagnosis (35%
      vs. 16%, p<0.006), or to have suffered a trauma to affected joints prior to
      diagnosis (44% vs. 19%, p<0.0002). Within the 1-year prior to disease diagnosis,
      controls reported slightly more streptococcal infections (p<0.2), infections with
      diarrhea and vomiting (p<0.3), and antibiotic use (p<0.09), although none of
      these results were statistically significant. Histories of any hepatitis,
      rubella, any bacterial infection, and having had a previous positive tuberculosis
      skin test were not significantly different between groups and were actually more
      often reported by the control subjects. SSc reported slightly more hepatitis B
      (p<0.08), more rheumatic fever (p<0.8) in past, and herpes zoster (p<0.4),
      although no differences reached significance. CONCLUSION: This study does not
      support that self-report of symptomatic infections are more likely to occur ever
      (prior to diagnosis) or within 1-year prior to symptom onset of SSc, or that
      vaccinations in adulthood trigger SSc.

PMID- 19088896
TI  - Incidence of Rheumatoid Arthritis in the Southern part of Denmark from 1995 to
      2001.
AB  - We estimated the incidence of rheumatoid arthritis in the southern part of
      Denmark from 1995 to 2001. At a rheumatology hospital serving a population of
      about 200 000 people over the age of 15, medical records were scrutinized. As
      case definition we used the tree and list format of 1987 American College of
      Rheumatology criteria for rheumatoid arthritis. The mean annual incidence rate
      per 100 000 person years was 40 in females, 21 in males, and 31 in females and
      males combined. The incidence of rheumatoid arthritis in Denmark is in accordance
      with recent studies from North America, the UK, and Northern European countries.
      The aetiology of rheumatoid arthritis is unknown but this study indicates that in
      these populations the exposure to non-genetic host and environmental aetiological
      factors is similar.

PMID- 19088897
TI  - Macrophage Tropism and Cytopathicity of HIV-1 Variants Isolated Sequentially from
      a Long-Term Survivor Infected with nef-Deleted Virus.
AB  - Long-term survival of human immunodeficiency virus type 1 (HIV-1) infection has
      been noted in rare cohorts of individuals infected with nef-deleted virus.
      Enhanced macrophage tropism and cytopathicity contribute to pathogenicity of wild
      type HIV-1. To better understand the pathogenesis of nef-deleted HIV-1, we
      analyzed the replication capacity and macrophage cytopathicity of nef-deleted HIV
      1 isolated sequentially from a long-term survivor during progression to AIDS (n=6
      isolates). Compared with controls, all nef-deleted viruses replicated to low
      levels in peripheral blood mononu-clear cells and monocyte-derived macrophages
      (MDM). One nef-deleted virus that was isolated on the development of AIDS caused
      high levels of syncytia in MDM similar to control viruses, but five viruses
      isolated from earlier times prior to AIDS onset caused only minimal
      cytopathicity. Together, these results suggest that enhanced cytopathicity of nef
      deleted HIV-1 for MDM can occur independently of replication capacity, and may
      contribute to the pathogenesis of nef-deleted HIV-1 infection.

PMID- 19088898
TI  - Molecular Epidemiology of Pseudomonas aeruginosa in the Intensive Care Units - A
      Review.
AB  - Pseudomonas aeruginosa is one of the leading nosocomial pathogens in intensive
      care units (ICU). This opportunist pathogen is commonly recovered from moist
      environments, and is also found colonizing 2.6 to 24% of hospitalized patients.
      We reviewed the recent literature that used highly discriminatory typing methods
      to precisely identify the reservoirs and modes of transmission of this
      microorganism in the ICU setting. In most ICUs, the endogenous flora was
      suspected to be the main source of infection compared to exogenous sources (other
      patients, the contaminated environment such as sinks or taps). However, the
      percentage of endogenous versus exogenous sources might vary considerably from
      one setting to another. Reasons for this include the compliance of health care
      workers to infection control measures, the contamination of the environment, and
      probably also the biology of the pathogen (intrinsic fitness factors). As P.
      aerugi-nosa is ubiquitous in the environment and colonizes up to 15% of
      hospitalized patients, eradication of the reservoir is difficult, if not
      impossible. Therefore, efforts should primarily focus on reinforcement of
      infection control measures to limit its transmission.

PMID- 19088899
TI  - Modeling of respiratory system dysfunction among nuclear workers: a preliminary
      study.
AB  - Numerous studies have reported on cancers among Mayak Production Association (PA)
      nuclear workers. Other studies have reported on serious deterministic effects of
      large radiation doses for the same population. This study relates to
      deterministic effects (respiratory system dysfunction) in Mayak workers after
      relatively small chronic radiation doses (alpha plus gamma). Because cigarette
      smoke is a confounding factor, we also account for smoking effects. Here we
      present a new empirical mathematical model that was introduced for simultaneous
      assessment of radiation and cigarette-smoking-related damage to the respiratory
      system. The model incorporates absolute thresholds for smoking- and radiation
      induced respiratory system dysfunction. As the alpha radiation dose to the lung
      increased from 0 to 4.36 Gy, respiratory function indices studied decreased,
      although remaining in the normal range. The data were consistent with the view
      that alpha radiation doses to the lung above a relatively small threshold (0.15
      to 0.39 Gy) cause some respiratory system dysfunction. Respiratory function
      indices were not found to be influenced by total-body gamma radiation doses in
      the range 0-3.8 Gy when delivered at low rates over years. However, significant
      decreases in airway conductance were found to be associated with cigarette
      smoking. Whether the indicated cigarette smoking and alpha radiation associated
      dysfunction is debilitating is unclear.

PMID- 19088901
TI  - Summary of dose-response modeling for developmental toxicity studies.
AB  - Developmental toxicity studies are an important area in the field of toxicology.
      Endpoints measured on fetuses include weight and indicators of death and
      malformation. Binary indicator measures are typically summed over the litter and
      a discrete distribution is assumed to model the number of adversely affected
      fetuses. Additionally, there is noticeable variation in the litter responses
      within dose groups that should be taken into account when modeling. Finally, the
      dose-response pattern in these studies exhibits a threshold effect. The threshold
      dose-response model is the default model for non-carcinogenic risk assessment,
      according to the USEPA, and is encouraged by the agency for the use in the risk
      assessment process. Two statistical models are proposed to estimate dose-response
      pattern of data from the developmental toxicity study: the threshold model and
      the spline model. The models were applied to two data sets. The advantages and
      disadvantages of these models, potential other models, and future research
      possibilities will be summarized.

PMID- 19088900
TI  - It's time for a new low-dose-radiation risk assessment paradigm--one that
      acknowledges hormesis.
AB  - The current system of radiation protection for humans is based on the linear-no
      threshold (LNT) risk-assessment paradigm. Perceived harm to irradiated nuclear
      workers and the public is mainly reflected through calculated hypothetical
      increased cancers. The LNT-based system of protection employs easy-to-implement
      measures of radiation exposure. Such measures include the equivalent dose (a
      biological-damage-potential-weighted measure) and the effective dose (equivalent
      dose multiplied by a tissue-specific relative sensitivity factor for stochastic
      effects). These weighted doses have special units such as the sievert (Sv) and
      millisievert (mSv, one thousandth of a sievert). Radiation-induced harm is
      controlled via enforcing exposure limits expressed as effective dose. Expected
      cancer cases can be easily computed based on the summed effective dose (person
      sievert) for an irradiated group or population. Yet the current system of
      radiation protection needs revision because radiation-induced natural protection
      (hormesis) has been neglected. A novel, nonlinear, hormetic relative risk model
      for radiation-induced cancers is discussed in the context of establishing new
      radiation exposure limits for nuclear workers and the public.

PMID- 19088902
TI  - Atomic bomb health benefits.
AB  - Media reports of deaths and devastation produced by atomic bombs convinced people
      around the world that all ionizing radiation is harmful. This concentrated
      attention on fear of miniscule doses of radiation. Soon the linear no threshold
      (LNT) paradigm was converted into laws. Scientifically valid information about
      the health benefits from low dose irradiation was ignored. Here are studies which
      show increased health in Japanese survivors of atomic bombs. Parameters include
      decreased mutation, leukemia and solid tissue cancer mortality rates, and
      increased average lifespan. Each study exhibits a threshold that repudiates the
      LNT dogma. The average threshold for acute exposures to atomic bombs is about 100
      cSv. Conclusions from these studies of atomic bomb survivors are: One burst of
      low dose irradiation elicits a lifetime of improved health.Improved health from
      low dose irradiation negates the LNT paradigm.Effective triage should include
      radiation hormesis for survivor treatment.

PMID- 19088903
TI  - Complex mixture-associated hormesis and toxicity: the case of leather tanning
      industry.
AB  - A series of studies investigated the toxicities of tannery-derived complex
      mixtures, i.e. vegetable tannin (VT) from Acacia sp. or phenol-based synthetic
      tannin (ST), and waste-water from tannin-based vs. chromium-based tanneries.
      Toxicity was evaluated by multiple bioassays including developmental defects and
      loss of fertilization rate in sea urchin embryos and sperm (Paracentrotus lividus
      and Sphaerechinus granularis), and algal growth inhibition (Dunaliella
      tertiolecta and Selenastrum capricornutum). Both VT and ST water extracts
      resulted in hormetic effects at concentrations ranging 0.1 to 0.3%, and toxicity
      at levels > or =1%, both in sea urchin embryo and sperm, and in algal growth
      bioassays. When comparing tannin-based tannery wastewater (TTW) vs. chromium
      based tannery effluent (CTE), a hormesis to toxicity trend was observed for TTW
      both in terms of developmental and fertilization toxicity in sea urchins, and in
      algal growth inhibition, with hormetic effects at 0.1 to 0.2% TTW, and toxicity
      at TTW levels > or =1%. Unlike TTW, CTE showed a monotonic toxicity increase from
      the lowest tested level (0.1%) and CTE toxicity at higher levels was
      significantly more severe than TTW-induced toxicity. The results support the view
      that leather production utilizing tannins might be regarded as a more
      environmentally friendly procedure than chromium-based tanning process.

PMID- 19088904
TI  - Isolation of the Bacteriophage DinoHI from Dichelobacter nodosus and its
      Interactions with other Integrated Genetic Elements.
AB  - The Gram-negative anaerobic pathogen Dichelobacter nodosus carries several
      genetic elements that integrate into the chromosome. These include the intA,
      intB, intC and intD elements, which integrate adjacent to csrA and pnpA, two
      putative global regulators of virulence and the virulence-related locus, vrl,
      which integrates into ssrA. Treatment of D. nodosus strains with ultraviolet
      light resulted in the isolation of DinoHI, a member of the Siphoviridae and the
      first bacteriophage to be identified in D. nodosus. Part of the DinoHI genome
      containing the packaging site is found in all D. nodosus strains tested and is
      located at the end of the vrl, suggesting a role for DinoHI in the transfer of
      the vrl by transduction. Like the intB element, the DinoHI genome contains a copy
      of regA which has similarity to the repressors of lambdoid bacteriophages,
      suggesting that the maintenance of DinoHI and the intB element may be co
      ordinately controlled.

PMID- 19088905
TI  - A novel and simple method for laboratory diagnosis of relapsing Fever
      borreliosis.
AB  - Relapsing fever caused by Borrelia bacteria is often obscured by malaria and
      incorrectly treated. Here a novel method for diagnosis is presented. The method
      is cheap, simple and requires minimal laboratory material. Despite its
      simplicity, the method shows surprisingly high sensitivity, detecting
      concentrations less than 10 bacteria/ml blood.

PMID- 19088906
TI  - Cloning, Purification, and Partial Characterization of the Halobacterium sp. NRC
      1 Minichromosome Maintenance (MCM) Helicase.
AB  - The MCM gene from the archaeon Halobacterium, with and without its intein, was
      cloned into an Escherichia coli expression vector, overexpressed and the protein
      was purified and antibodies were generated. The antibodies were used to
      demonstrate that in vivo only the processed enzyme, without the intein, could be
      detected.

PMID- 19088907
TI  - Biochemical and Genetic Characterization of PspE and GlpE, Two Single-domain
      Sulfurtransferases of Escherichia coli.
AB  - The pspE and glpE genes of Escherichia coli encode periplasmic and cytoplasmic
      single-domain rhodaneses, respectively, that catalyzes sulfur transfer from
      thiosulfate to thiophilic acceptors. Strains deficient in either or both genes
      were constructed. Comparison of rhodanese activity in these strains revealed that
      PspE provides 85% of total rhodanese activity, with GlpE contributing most of the
      remainder. PspE activity was four times higher during growth on glycerol versus
      glucose, and was not induced by conditions that induce expression of the psp
      regulon. The glpE/pspE mutants displayed no apparent growth phenotypes,
      indicating that neither gene is required for biosynthesis of essential sulfur
      containing molecules. PspE was purified by using cation exchange chromatography.
      Two distinct active peaks were eluted and differed in the degree of stable
      covalent modification, as assessed by mass spectrometry. The peak eluting
      earliest contained the equivalent mass of two additional sulfur atoms, whereas
      the second peak contained mainly one additional sulfur. Kinetic properties of
      purified PspE were consistent with catalysis occurring via a double-displacement
      mechanism via an enzyme-sulfur intermediate involving the active site cysteine.
      K(m)s for SSO(3) (2-) and CN(-) were 2.7 mM and 32 mM, respectively, and k(cat)
      was 64(s-1). The enzyme also catalyzed transfer of sulfur from thiosulfate to
      dithiothreitol, ultimately releasing sulfide.

PMID- 19088908
TI  - A Case of Helicobacter cinaedi Bacteraemia in a Previously Healthy Person with
      Cellulitis.
AB  - Helicobacter cinaedi is an infrequent, but well recognized cause of
      gastroenteritis in immunosuppressed patients. Here we report a case of an extra
      intestinal infection in a previous healthy 61-year old heterosexual male. Focus
      for the infection was most likely cellulitis on the lower right leg. The
      bacterium was cultured from blood twice within one week. Electron microscopy of
      the isolate visualized bipolar flagella. Partial DNA sequencing of the 16S rRNA
      gene and phenotypic characterization of the isolate established the species
      diagnosis. The patient was treated with rifampicin. After end of treatment blood
      cultures were negative and the cellulitis had disappeared.

PMID- 19088909
TI  - Alteration of Membrane Permeability of Bacteria and Yeast by High Frequency
      Alternating Current (HFAC).
AB  - AIMS: Endox((R)) Endodontic System (Endox) is used for endodontic treatment by a
      high frequency alternating current (HFAC). This device damaged the envelopes of
      spores and vegetative organisms. If the integrity of the envelope is compromised,
      the transit of compounds in the two directions is possible. This latter aspect
      was investigated here. METHODS: The instrument delivered a 60ms pulse at a
      frequency 300 kHz, and power 800 KV/m. DNA transfer was verified using
      Escherichia coli K-12 strain carrying a non conjugative plasmid pBP517 (gyrA(+))
      as donor and a rifampicin and nalidixic acid resistant recipient. 0.2 ml of
      mixture of donor and recipient strains in saline was exposed to HFAC and plated
      on selective media. Uptake of antimicrobials and a delay in re-growth was
      assessed exposing the strains to HFAC. RESULTS: Plasmid transfer was detected
      under different experimental conditions. From 9 to 27 recombinants were found.
      Representative recombinants cured from plasmid showed the original phenotype.
      HFAC promoted the uptake of ineffective antibiotics, and induces a 1 h of delay
      in re-growth on the strains. CONCLUSIONS: Endox exhibited an effect on
      microrganisms which is reminiscent with that occuring in electroporation, but
      with a mode of action that saved materials and time.

PMID- 19088912
TI  - Bacterial Concentration and Diversity within Repetitive Aliquots Collected from
      Replicate Continuous-Flow Bioreactor Cultures.
AB  - The aim of this study was to determine the reproducibility of small volume repeat
      sampling from replicate bioreactors with stabilized continuous-flow chicken cecal
      bacterial communities. Bacterial concentration and diversity were analyzed by
      phenotypic, biochemical and ribotype analysis. Significant differences in
      concentrations and variations in diversity were found in replicate bioreactors.

PMID- 19088910
TI  - Ecology of lactobacilli in the oral cavity: a review of literature.
AB  - Lactobacilli appear in the oral cavity during the first years of a child's life.
      Their presence depends on numerous factors such as the presence of ecological
      niches e.g. natural anfractuosities of the teeth.A strong correlation has been
      established between the saliva Lactobacillus count and dental caries, the higher
      the DMF index, the higher the number of children harbouring a high Lactobacillus
      count.Among children, the presence of lactobacilli in coronal caries is
      incontestable. Among adults, lactobacilli are found in root caries. Since 1999,
      taxonomical revisions make it difficult to interpret the results obtained in the
      numerous previous studies carried out on the identification of oral lactobacilli,
      but whatever the sampling method or the identification technique, the carious
      site or the age of sampled subjects, most species belong to the Lactobacillus
      casei group.This is important because if a specific correlation can be found
      between few species of lactobacilli and caries a better understanding of their
      properties could allow the development of new tools for prevention.

PMID- 19088911
TI  - Toll-like receptors and viruses: induction of innate antiviral immune responses.
AB  - Induction of antiviral innate immune responses depends on a family of innate
      immune receptors, the Toll-like receptors (TLR). TLR mediate the antiviral immune
      responses by recognizing virus infection, activating signaling pathways and
      inducing the production of antiviral cytokines and chemokines. ssRNA and dsRNA
      viruses can be recognized by TLR7/8 and TLR3, respectively. TLR receptors are
      also involved in the recognition of viruses containing genomes rich in CpG DNA
      motifs as well as envelope glycoproteins. Cytoplasmic recognition of dsRNA by RNA
      helicases such as RIG-I and MDA5 provides another means of recognizing viral
      nucleic acid. In order to counteract the innate host immune system viruses
      evolved mechanisms that block recognition and signaling through pattern
      recognition receptors, such as TLRs and RNA helicases. Recently, TLR agonists
      represent a promising approach for the treatment of infectious diseases. This
      review will focus on the current knowledge of TLR-mediated immune responses to
      several viral infections.

PMID- 19088913
TI  - The Susceptibility of Candida albicans to Gamma-Radiations and Ketoco-nazole
      Depends on Transitional Filamentation.
AB  - The virulence of C. albicans is associated with the transitional evolution from
      yeast to filamentous forms. We were interested in the effects amphotericin B
      (AMB), ketoconazole (KTC) and gamma-radiations might have on these broadly
      defined phenotypes as determined by the CFU procedure. By using collagen gel as
      the 3-dimensional support of cell culture, diverse experimental conditions were
      contemplated in order to modulate the differentiation of Candida during sessile
      and planktonic growth. These conditions included the co-culture with human
      epithelial and endothelial cells and treatment with farnesol, tyrosol and
      conditioned medium from P. aeruginosa. The overall results were as follows: 1)
      The survival of Candida was inhibited by the exposure to gamma-radiations, but
      only after the organism was induced to progress into excess filamentation, while
      in normal growth conditions it proved to be radioresistant; 2) AMB inhibited the
      growth of yeast forms, while KTC was specifically toxic to filamentous forms and
      3) the combined treatment of filamentous Candida with KTC and gamma-radiations
      resulted in the synergistic inhibition of the organism. These findings indicate
      that both the radiosensitivity of C. albicans and its response to the synergistic
      effects of gamma-radiations and KTC are filamentation-dependent pharmacological
      processes.

PMID- 19088914
TI  - Influence of Nitrogen Source on 2,4-diacetylphloroglucinol Production by the
      Biocontrol Strain Pf-5.
AB  - The production of 2,4-diacetylphloroglucinol (DAPG) by the biocontrol agent
      Pseudomonas fluorescens Pf-5 was studied in nutrient-solution based media with
      varying nitrogen content. No production of DAPG was observed when organic
      nitrogen was omitted from the media, regardless of the inorganic nitrogen source
      used. Furthermore, a micromolar concentration range of organic nitrogen was
      insufficient to sustain production. When a millimolar concentration range of
      organic nitrogen was used, DAPG production was observed in the medium with
      ammonium as the inorganic nitrogen source. No production was observed in the
      treatments with ammonium and nitrate or nitrate only, despite growth of the
      bacterial strain being the same for all treatments. These results suggest that it
      is possible to manipulate the nutrient solution to increase the reliability and
      efficacy of biological control agents.

PMID- 19088915
TI  - In vitro Antimicrobial Activity of Ampicillin-Ceftriaxone and Ampicillin
      Ertapenem Combinations Against Clinical Isolates of Enterococcus faecalis with
      High Levels of Aminoglycoside Resistance.
AB  - This paper reports on the in vitro antimicrobial activity of ampicillin
      ceftriaxone and ampicillin-ertapenem combinations against five strains of E.
      faecalis with high-level aminoglycoside resistance recovered from blood of
      septicemic patients. Double disk diffusion test and time killing curves were
      used. A bacteriostatic synergistic effect between ampicillin and ceftriaxone was
      detected using the disk diffusion assay for three of the five enterococcal
      strains studied. With the same three isolates enhanced bactericidal activity was
      also observed using time killing experiments. Overall, for these three strains,
      after 24 hr of contact, a decrease >/= 2 log(10) from the initial bacterial
      inoculum was registered with most ampicillin-ceftriaxone combinations, reaching
      with some of them a colony reduction >/= 3 log(10). This bactericidal interaction
      was negatively influenced increasing the bacterial inoculum. In all five isolates
      neither a bacteriostatic nor a bactericidal cooperation was observed for
      ampicillin combined with 2 mg/l of ertapenem.This investigation broadened the
      evidence of antimicrobial synergism in vitro between ampicillin and ceftriaxone
      in selected strains of Enterococcus faecalis with high-level aminoglycoside
      resistance.

PMID- 19088916
TI  - Infective Arthritis: Bacterial 23S rRNA Gene Sequencing as a Supplementary
      Diagnostic Method.
AB  - Consecutively collected synovial fluids were examined for presence of bacterial
      DNA (a 700-bp fragment of the bacterial 23S rRNA gene) followed by DNA sequencing
      of amplicons, and by conventional bacteriological methods. One or more
      microorganisms were identified in 22 of the 227 synovial fluids (9,7%)
      originating from 17 patients. Sixteen of the patients had clinical signs of
      arthritis. For 11 patients molecular and conventional bacterial examinations were
      in agreement. Staphylococcus aureus, Streptococcus dysgalactiae subspecies
      equisimilis and Streptococcus pneumoniae, were detected in synovial fluids from
      6, 2 and 2 patients, respectively. In 3 patients only 23S rRNA analysis was
      positive; 2 synovial fluids contained S. dysgalactiae subspecies equisimilis and
      1 S. pneumoniae). The present study indicates a significant contribution by PCR
      with subsequent DNA sequencing of the 23S rRNA gene analysis in recognizing and
      identification of microorganisms from synovial fluids.

PMID- 19088918
TI  - Identification of a Novel Regulator for the Escherichia coli fit Iron Transport
      System.
AB  - The Escherichia coli fit iron transport system consists of 6 genes, fitA, B, C,
      D, E and fitR. Based on in silico analysis, FitA-E composes a typical bacterial
      iron transporter, while FitR was deduced to be a regulator. In this paper the
      regulation of fit expression by FitR was studied using a quantitative RT-PCR
      technique and a lacZ reporter assay. It was found that fit expression was
      repressed when FitR was over-expressed and de-repressed when fitR was knocked out
      by mutation. When the mutation in fitR was complemented in trans- with the wild
      type fitR gene, repression of fit expression by FitR was restored. Finally,
      recombinant FitR was found to bind to the fit promoter DNA when employed in an
      electrophoretic mobility-shift assay. These results demonstrated that fitR
      encodes an auto-repressor for the E. colifit system.

PMID- 19088917
TI  - The Two-Component Regulatory System VicRK is Important to Virulence of
      Streptococcus equi Subspecies equi.
AB  - This study aims at evaluating the importance of the two-component regulatory
      system VicRK to virulence of the horse pathogen Streptococcus equi subspecies
      equi and the potential of a vicK mutant as a live vaccine candidate using mouse
      infection models. The vicK gene was deleted by gene replacement. The DeltavicK
      mutant is attenuated in virulence in both subcutaneous and intranasal infections
      in mice. DeltavicK grows less slowly than the parent strain but retains the
      ability of S. equi to resist to phagocytosis by polymorphoneuclear leukocytes,
      suggesting that the vicK deletion causes growth defect. DeltavicK infection
      protects mice against reinfection with a wild-type S. equi strain. Intranasal
      DeltavicK infection induces production of anti-SeM mucosal IgA and systemic IgG.
      These results indicate that VicRK is important to S. equi growth and virulence
      and suggest that DeltavicK has the potential to be developed as a live S. equi
      vaccine.

PMID- 19088919
TI  - The Catalytic Product of Pentachlorophenol 4-Monooxygenase is Tetra
      chlorohydroquinone rather than Tetrachlorobenzoquinone.
AB  - Pentachlorophenol 4-monooxygenase (PcpB) catalyzes the hydroxylation of
      pentachlorophenol in the pentachlorophenol biodegradation pathway in Sphingobium
      chlorophenolicum. Previous studies from two different research groups proposed
      oppositely that the catalytic product of PcpB was tetrachlorohydroquinone (TCHQ)
      and tetrachlorobenzoquinone (TCBQ). We re-examined the identity of the catalytic
      product of PcpB, because TCHQ and TCBQ are present in a redox-equilibrium in
      aqueous solutions and the chemical reagents NADPH, ethyl acetate and glutathione
      used for the product detection in the previous studies may shift the redox
      equilibrium. In this study, we investigated the effects of NADPH, ethyl acetate
      and glutathione on the redox-equilibrium and product distribution. Under newly
      designed experimental conditions, we confirmed unambiguously that the catalytic
      product of PcpB is TCHQ instead of TCBQ. We also propose that TCBQ may be
      produced non-specifically by peroxidases within the bacterial cells and that TCBQ
      reductase (PcpD) might act as a self-protective rather than a PCP-degradation
      enzyme.

PMID- 19088921
TI  - Organoleptic Analysis of Doughs Fermented with Yeasts From A Nigerian Palm Wine
      (Elaeis guineensis) and Certain Commercial Yeasts.
AB  - Yeasts isolated from a freshly tapped palm wine obtained from Akure, Nigeria were
      identified as Schizosaccharomyces pombe, Saccharomyces cerevisiae, Debaryomyces
      hansenii, Geotrichum lactis and Zygosaccharomyces rouxii. Each of the isolates
      was used to ferment wheat flour dough and baked. Sensory analysis of the doughs
      was carried out using leavening, texture, aroma, taste and appearance.
      Saccharomyces cerevisiae performed best in leavening the dough while Debaryomyces
      hansenii produced doughs with the best taste and aroma. Appearances of the doughs
      made with all the isolated yeasts did not differ significantly (P>0.05) from that
      of the dough that lacked yeast.

PMID- 19088920
TI  - The Inactivation of a New Peptidoglycan Hydrolase Pmp23 Leads to Abnormal Septum
      Formation in Streptococcus pneumoniae.
AB  - The bacterial peptidoglycan is the major component of the cell wall which
      integrity is essential to cell survival. In a previous work, we identified, in
      the positive-Gram pathogen Streptococcus pneumoniae , a unique protein containing
      a new putative peptidoglycan hydrolytic domain named PECACE (PEptidoglycan
      CArbohydrate Cleavage Enzyme). In this study, we characterise the physiological
      function of this protein called Pmp23 (Pneumococcal Membrane Protein of 23 kDa).
      A cell wall hydrolytic activity is observed with the recombinant protein.
      Inactivation of the pmp23 gene in the pneumococcus led to a decreased
      flocculation, an increased sensitivity to beta-lactam antibiotics and
      morphological alterations affecting the formation and localisation of the
      division septa. Taken together these observations indicate that Pmp23 is a
      hydrolase whose function is linked to peptidoglycan metabolism at the septum
      site.

PMID- 19088923
TI  - Adjuvant lipiodol I-131 after curative resection/ablation of hepatocellular
      carcinoma.
AB  - AIM: A total of 329 patients with hepatocellular carcinoma have been treated at
      our unit since 1990. Following the randomized controlled trial in Hong Kong by
      Lau et al. in 1999, patients have been offered adjuvant lipiodol I-131. The aim
      of this study was to determine the effectiveness of adjuvant lipiodol I-131,
      following potentially curative surgery with resection and/or ablation, on overall
      and disease-free survival rates. MATERIAL AND METHODS: The prospectively updated
      hepatocellular carcinoma database was analysed retrospectively. A total of 34
      patients were identified to have received adjuvant lipiodol I-131 post-curative
      treatment with surgical resection and/or ablation. Patient demographics,
      clinical, surgical, pathology, and survival data were collected and analysed.
      RESULTS: Three patients received ablation alone, 24 resection, and 7 resection
      and ablation. Of the 34 patients treated, there were 2 possible cases of
      treatment-related fatality (pneumonitis and liver failure). Potential prognostic
      factors studied for effect on survival included age, gender, serum AFP
      concentration, Child-Pugh score, cirrhosis, tumor size, portal vein tumor
      thrombus, tumor rupture, and vascular and margin involvement. The median follow
      up duration was 23.3 months. The overall median survival was 40.1 months, while
      the overall survival rates at 1, 2, 3, and 4 years were 87.1%, 71.7%, 60.7%, and
      49.6%, respectively. Median duration to recurrence was 22.3 months. CONCLUSION:
      Administration of adjuvant lipiodol I-131 is associated with good overall
      survival.

PMID- 19088924
TI  - Treatment response to transcatheter arterial embolization and chemoembolization
      in primary and metastatic tumors of the liver.
AB  - INTRODUCTION: Transcatheter arterial embolization (TAE) and chemoembolization
      (TACE) are increasingly used to treat unresectable primary and metastatic liver
      tumors. The purpose of this study was to determine the objective response to TAE
      and TACE in unresectable hepatic malignancies and to identify clinicopathologic
      predictors of response. MATERIALS AND METHODS: Seventy-nine consecutive patients
      who underwent 119 TAE/TACE procedures between 1998 and 2006 were reviewed. The
      change in maximal diameter of 121 evaluable lesions in 56 patients was calculated
      from pre and post-procedure imaging. Response rates were determined using
      Response Evaluation Criteria in Solid Tumors (RECIST) guidelines. The Kaplan
      Meier method was used to compare survival in responders vs. non-responders and in
      primary vs. metastatic histologies. RESULTS: TAE and TACE resulted in a mean
      decrease in lesion size of 10.3%+/-1.9% (p<0.001). TACE (vs. TAE) and carcinoid
      tumors were associated with a greater response (p<0.05). Lesion response was not
      predicted by pre-treatment size, vascularity, or histology. The RECIST partial
      response (PR) rate was 12.3% and all partial responders were in the TACE group.
      Neuroendocrine tumors, and specifically carcinoid lesions, had a significantly
      greater PR rate (p<0.05). Overall survival, however, was not associated with
      histology or radiologic response. DISCUSSION: TAE and TACE produce a significant
      objective treatment response by RECIST criteria. Response is greatest in
      neuroendocrine tumors and is independent of vascularity and lesion size. TACE
      appears to be superior to TAE. Although an association of response with improved
      survival was not demonstrated, large cohort studies are necessary to further
      define this relationship.

PMID- 19088925
TI  - Implementation of a multidisciplinary treatment team for hepatocellular cancer at
      a Veterans Affairs Medical Center improves survival.
AB  - Several methods of treatment for hepatocellular carcinoma (HCC) are often used in
      combination for either palliation or cure. We established a multidisciplinary
      treatment team (MDTT) at the San Francisco Veterans Affairs Medical Center in
      November 2003 and assessed whether aggressive multimodality treatment strategies
      may affect survival. A prospective database was established and follow-up
      information from patients with presumed HCC was collected up to November 2006.
      Information from the American College of Surgeons (ACS) cancer registry from
      January 2000 to November 2003 identified patients with HCC that were evaluated at
      the same institution prior to the establishment of the MDTT. The establishment of
      a MDTT resulted in the doubling of patient referrals for treatment. Significantly
      more patients were evaluated at earlier stages of disease and received either
      palliative or curative therapies. The overall survival (p<0.0001) and length of
      follow-up (p<0.05) were significantly improved after the establishment of the
      MDTT. Stage-by-stage comparisons indicate that aggressive multimodality therapy
      conferred significant survival advantage to patients with American Joint
      Commission on Cancer (AJCC) stage II HCC (odds ratio 15.50, p<0.001).
      Multidisciplinary collaboration and multimodality treatment approaches are
      important in the management of hepatocellular carcinoma and improves patient
      survival.

PMID- 19088926
TI  - Intention to treat survival following liver transplantation for hepatocellular
      carcinoma within a donor service area.
AB  - BACKGROUND: This study aimed to assess the impact of wait times on patient
      survival following liver transplantation for hepatocellular carcinoma (HCC) in a
      single donor service area. PATIENTS AND METHODS: Patients listed in the New
      England Organ Bank (NEOB) from 1996 to 2005 for liver transplantation with a
      diagnosis of HCC were identified from the United Network for Organ Sharing
      database. The following data were extracted: date of listing, date removed from
      the wait list, indication for wait list removal, patient death and date of last
      known follow-up. Kaplan-Meier survival estimates were calculated from the time of
      listing for transplant (intention to treat liver transplant survival, ITT OLT)
      and compared to those calculated from the date of transplant (liver transplant,
      OLT). RESULTS: There were 63 new registrations to the transplant list during the
      study period. Sixty-one patients were removed from the waiting list: transplanted
      41 (65%), death seven (11%), candidate condition deteriorated/too sick to
      transplant eight (13%), medically unsuitable one (2%), other one (2%),
      transferred to another center two (3%), and transplanted at another center one
      (2%). Three-year survival following liver transplantation for primary liver
      cancer was 85%. When the results were analyzed using an intention to treat
      analysis there was a 10-20% decrease in survival rate at every time point due to
      wait list drop-out. CONCLUSION: Wait list drop-out adversely affects liver
      transplant survival in transplant centers served by the NEOB. These data should
      be considered when recommending transplant versus resection as first line therapy
      for stage I or II HCC in our region.

PMID- 19088927
TI  - Iatrogenic bile duct injury--a cost analysis.
AB  - INTRODUCTION: Iatrogenic bile duct lesions following cholecystectomy represent a
      feared complication occurring in up to 0.9%. The aim of the present study was to
      estimate the total cost associated with both minor and major bile duct injuries.
      MATERIAL AND METHODS: Detailed information on 24 consecutive patients, out of
      which 14 were considered to have minor and 10 patients considered as having major
      bile duct injury, provided the underlying information that rendered calculations
      on average individual costs for both groups of injuries. RESULTS AND DISCUSSION:
      Calculating individual costs for minor and major bile duct injuries with actual
      incidences of cholecystectomies performed and the incidence of iatrogenic bile
      duct injury demonstrated that the total costs, including in-hospital cost, sick
      leave and loss of production, were substantial. For the management of minor bile
      duct injuries costs were within the range of 136,787-159,585 EUR and for the
      management of major bile duct injuries from 336,903-449,204 EUR per million
      inhabitants and year. The total costs for the management of all types of bile
      duct injuries were thus within the range of 473,690-608,789 EUR per million
      inhabitants annually for the society.

PMID- 19088928
TI  - The impact of tumor extent (T stage) and lymph node involvement (N stage) on
      survival after surgical resection for gallbladder adenocarcinoma.
AB  - INTRODUCTION: Tumor extent (T stage) and lymph node involvement (N stage) have a
      known combined negative effect on survival in patients with gallbladder
      adenocarcinoma, but the independent effects of these factors have been less well
      described. We investigated whether T stage and N stage independently predict
      survival after surgery for gallbladder adenocarcinoma. METHODS: We queried the
      Surveillance, Epidemiology and End Results database for patients treated with
      surgical resection for gallbladder adenocarcinoma between 1988 and 2004. Cases
      were stratified by disease severity based on tumor extent and nodal involvement.
      Kaplan-Meier and Cox regression methods were used to test the effect of disease
      severity and to develop multivariate models of the effects of demographic and
      clinical covariates on survival. Univariate and multivariate models were tested
      in the entire cohort and in a subsample with pathologically confirmed lymph node
      status. RESULTS: Four thousand and forty-eight patients who survived the
      immediate perioperative period comprised the full cohort. The subsample with
      pathologically confirmed lymph node status included 1298 patients. Age, gender,
      radiation treatment, tumor grade, tumor extent and lymph node status had
      statistically significant independent effects on survival in both models (all
      p<0.03). After accounting for T by N stage interactions, both tumor extent (1.21
      < or = HR < or = 3.81, all p < or = 0.005) and lymph node involvement (1.80 < or
      = HR < or = 2.84, p<0.001) had independent effects on survival. CONCLUSIONS:
      Tumor extent and lymph node metastases are independent predictors of survival
      after surgical resection for gallbladder adenocarcinoma. Tumor penetration of the
      gallbladder wall and pathologically confirmed lymph node involvement each carry
      poor prognosis.

PMID- 19088929
TI  - Management of benign biliary strictures by percutaneous interventional radiologic
      techniques (PIRT).
AB  - INTRODUCTION: Some biliary strictures may be manageable by percutaneous
      interventional radiologic techniques (PIRT), but long-term efficacy of this
      approach is scarce. METHODS: We reviewed retrospectively all patients with
      biliary strictures secondary to traumatic bile duct injury or strictured
      bilioenteric anastomoses. Patients in whom the initial management was by PIRT
      from 1998 through 2003 were selected. Subjects with sclerosing cholangitis,
      hepatic transplantation, or malignant strictures were excluded. Data were
      obtained from medical records and/or direct patient contact. Comparisons were
      made by Fisher's exact test and Wilcoxon rank-sum test. RESULTS: Twenty-seven
      patients with biliary strictures were treated by PIRT. Mean age was 54 years
      (range 11-86). Most frequent etiology was laparoscopic cholecystectomy injury in
      11 patients (41%). Eight patients (29%) had undergone biliary resection for
      malignancy, seven (26%) a pancreatoduodenectomy, and one for presumed ischemic
      cholangiopathy; no strictures were secondary to neoplastic recurrence. PIRT was
      successful in 10 of 11 patients (91%) with short, isolated bile duct strictures
      secondary to laparoscopic cholecystectomy and in seven of 15 patients (41%) with
      strictured bilioenteric anastomosis, but not in the patient with ischemic
      cholangiopathy. Twenty patients (74%) were stent-free at follow-up. Anastomotic
      biliary strictures were more likely to fail PIRT than isolated strictures
      secondary to laparoscopic cholecystectomy injury (p=0.02). CONCLUSION:
      Percutaneous balloon dilatation and stenting can be an effective strategy for
      patients with bile duct strictures, especially short bile duct strictures after
      laparoscopic cholecystectomy. Anastomotic strictures are associated with less
      good results when managed by PIRT but are successful in up to 40% of patients.

PMID- 19088930
TI  - An audit of ambulatory laparoscopic cholecystectomy in a Singapore institution:
      are we ready for day-case laparoscopic cholecystectomy?
AB  - BACKGROUND: Day-Case laparoscopic cholecystectomy (LC) is practiced in many
      countries. However, this has yet to be widely accepted in Singapore. This study
      aims to determine the potential success rate of day-case LC in our institution.
      PATIENT AND METHODS: We retrospectively assessed the proportion of our Ambulatory
      Surgery 23 hour (AS23) LC patients that met discharge criteria. Our proposed same
      day discharge criteria include minimal pain, ability to tolerate feeds, ambulate
      independently and void spontaneously after 6-8 hours of monitoring. RESULTS: From
      January 2005 to December 2006, of 405 patients listed for elective LC, 84% of
      patients were admitted to our AS23 ward. Patients with previous biliary sepsis or
      pancreatitis or who need laparoscopic common bile duct exploration (LCBDE) were
      included. The other 66 were admitted as inpatient. Forty-one of them were
      admitted due to conversion. A history of cholecystitis or cholangitis was a
      significant predictor of conversion to open surgery (OR=5.73 and 5.74
      respectively, p<0.001). Of the 339 patients, 66% of them fulfilled all four
      criteria within eight hours of monitoring. Therefore, based on an intention-to
      treat analysis, 51.2% fulfilled all four criteria and could potentially be
      discharged the same day. No predictor for failure was identified, including
      presence of co-morbidities, duration of operation, surgeon's grade and additional
      procedures like LCBDE. CONCLUSION: Using our current inclusion criteria, we
      projected a success rate of at least 50% with the implementation of day-case LC.
      With the attendant advantages of cost savings and reduced resource utilization,
      it is therefore worthwhile to start it in Singapore.

PMID- 19088931
TI  - Does PET-CT scan have a role prior to radical re-resection for incidental
      gallbladder cancer?
AB  - BACKGROUND: Radical re-resection is offered to patients with non-metastatic,
      invasive, incidental gallbladder cancer. Data evaluating (18)F-fluorodeoxyglucose
      positron emission tomography-computed tomography ((18)F-FDG PET-CT) in patients
      with incidental gallbladder cancer is sparse. AIM: To evaluate the efficacy of
      integrated (18)F-FDG PET-CT in determining occult metastatic or residual local
      regional disease in patients with incidental gallbladder cancer. METHODS:
      Patients referred with incidental gallbladder cancer for radical re-resection
      were evaluated using multidetector computed tomography (MDCT) and PET-CT. Based
      on preoperative imaging, 24 out of 92 patients were found suitable for surgery.
      The two imaging modalities were evaluated with respect to residual and resectable
      disease. RESULTS: In determining residual disease, MDCT had a sensitivity and
      positive predictive value (PPV) of 42.8%, each, while PET-CT had a sensitivity
      and PPV of 28.5 and 20%, respectively. In determining resectability, MDCT had a
      sensitivity, PPV, and accuracy of 100, 87.5, and 87.5%, respectively, as compared
      to PET-CT (sensitivity=100%, PPV=91.3%, accuracy=91.6%). CONCLUSIONS: From our
      study, it appears that in patients with incidental gall bladder cancer without
      metastatic disease, PET-CT and MDCT seem to have roles complementing each other.
      PET-CT was able to detect occult metastatic or residual local-regional disease in
      some of these patients, and seems to be useful in the preoperative diagnostic
      algorithm of patients whose MDCT is normal or indicates locally advanced disease.

PMID- 19088932
TI  - Ten-year experience in the management of gallbladder cancer from a single
      hepatobiliary and pancreatic centre with review of the literature.
AB  - BACKGROUND: There is no consensus regarding the optimum surgical approach to
      gallbladder cancer. This study reviews the management of gallbladder cancer in a
      single unit. METHODS: Retrospective study of 73 consecutive patients diagnosed
      with gallbladder cancer. Twenty-three patients underwent surgery with curative
      intent (surgical group), 28 patients underwent exploratory surgery but had
      inoperable disease (surgically inoperable group) and 22 patients had inoperable
      disease radiologically (radiologically inoperable group). Within the surgical
      group, nine patients (cholecystectomy group) were diagnosed with gallbladder
      cancer after routine cholecystectomy. RESULTS: The inoperable groups had
      significantly higher bilirubin and alkaline phosphatase (ALP) than the surgical
      group (p=0.02 and p<0.01, respectively). Age>68, white cell count (WCC)>7.6 x
      109/L, platelet>345 x 109/L, bilirubin>16 mol/L, ALP >124 iu/L and sodium < or =
      137 mmol/L were markers of inoperability. Age, haemoglobin and
      neutrophil:lymphocyte ratio (NLR) were predictors for survival following surgery
      (p=0.04, p=0.01 and p<0.01, respectively). The surgical and cholecystectomy
      groups had significantly higher median survivals than the surgically and
      radiologically inoperable groups (18.97 and 26.17 months versus 5.03 and 12.20
      months, p=0.04). CONCLUSION: Curative surgical resection of gallbladder cancer
      improved survival. Exploratory laparotomy which revealed inoperable disease
      reduced survival. Preoperative WCC, platelet, bilirubin and ALP may be used as
      additional discriminators during the investigation and work up prior to surgery.

PMID- 19088933
TI  - Use of activated protein C has no avail in the early phase of acute pancreatitis.
AB  - OBJECTIVES: Sepsis and acute pancreatitis have similar pathogenetic mechanisms
      that have been implicated in the progression of multiple organ failure.
      Drotrecogin alfa, an analogue of endogenous protein C, reduces mortality in
      clinical sepsis. Our objective was to evaluate the early therapeutic effects of
      activated protein C (APC) in a rat model of acute necrotizing pancreatitis.
      SUBJECTS AND METHOD: Acute necrotizing pancreatitis was induced by intraductal
      injection of 5% Na taurocholate. Hourly bolus injections of saline or recombinant
      human APC (drotrecogin alfa) was commenced via femoral venous catheter four hours
      after the induction of acute pancreatitis. The experiment was terminated nine
      hours after pancreatitis induction. Animals in group one (n=20) had a sham
      operation while animals in group two (n=20) received saline and animals in group
      three (n=20) received drotrecogin alfa boluses after acute pancreatitis
      induction. Pancreatic tissue for histopathologic scores and myeloperoxidase,
      glutathione reductase, glutathione peroxidase, and catalase activities were
      collected, and blood for serum amylase, urea, creatinine, and interleukin-6
      measurements was withdrawn. RESULTS: Serum amylase activity was significantly
      lower in the APC treated group than the untreated group (17,435+/-432 U/L vs.
      27,426+/-118 U/L, respectively). While the serum interleukin-6 concentration in
      the APC untreated group was significantly lower than the treated group (970+/-323
      pg/mL vs. 330+/-368 pg/mL, respectively). CONCLUSION: In the early phase of acute
      pancreatitis, drotrecogin alfa treatment did not result in a significant
      improvement in oxidative and inflammatory parameters or renal functions.

PMID- 19088934
TI  - Striving for a better operative outcome: 101 pancreaticoduodenectomies.
AB  - Pancreaticoduodenectomy (PD), once carried high morbidity and mortality, is now a
      routine operation performed for lesions arising from the pancreatico-duodenal
      complex. This study reviews the outcome of 101 pancreaticoduodenectomies
      performed after formalization of HepatoPancreatoBiliary (HPB) unit in the
      Department of Surgery. A prospective database comprising of patients who
      underwent PD was set up in 1999. Retrospective data for patients operated between
      1996 and 1999 was included. One hundred and one cases accrued over 10 years from
      1996 to 2006 were analysed using SPSS (Version 12.0). The mean age of our cohort
      of patients was 61+/-12 years with male to female ratio of 2:1. The commonest
      clinical presentations were obstructive jaundice (64%) and abdominal pain (47%).
      Majority had malignant lesions (86%) with invasive adenocarcinoma of the head of
      pancreas being the predominant histopathology (41%). Median operative time was
      315 (180-945) minutes. Two-third of our patients had pancreaticojejunostomy (PJ)
      while the rest had pancreaticogastrostomy (PG). There were five patients with
      pancreatico-enteric anastomotic leak (5%), three of whom (3%) were from PJ
      anastomosis. Overall, in-hospital and 30-day mortality were both 3%. The median
      post-operative length of stay (LOS) was 15 days. Using logistic regressions, the
      post-operative morbidity predicts LOS following operation (p<0.005). The strategy
      in improving the morbidity and mortality rates of pancreaticoduodenectomies lies
      in the subspecialization of surgical services with regionalization of such
      complex surgeries to high volume centers. The key success lies in the dedication
      of staffs who continues to refine the clinical care pathway and standardize
      management protocol.

PMID- 19088935
TI  - Antecolic gastrointestinal reconstruction with pylorus dilatation. Does it
      improve delayed gastric emptying after pylorus-preserving
      pancreaticoduodenectomy?
AB  - OBJECTIVE: The aim of our study focuses upon prevention of delayed gastric
      emptying (DGE) after pancreaticoduodenectomy using a alternative reconstruction
      procedure. METHOD: Forty consecutive patients underwent a typical pylorus
      preserving pancreaticoduodenectomy (PPPD) with antecolic reconstruction in a two
      year period (January 2002 until January 2004), while a similar group of 40
      consecutive patients underwent PPPD with application of pyloric dilatation
      between January 2004 and January 2006. Early and late complications were compared
      between the two groups. RESULTS: DGE occurred significantly more often in the
      group of patients treated by the classical PPPD technique (nine patients -22%)
      compared with those operated on with the addition of pyloric dilatation technique
      (two patients -5%) (p<0.05). The incidence of other complications did not differ
      significantly between the two groups. CONCLUSIONS: The application of dilatation
      may decrease the incidence of DGE after PPPD and facilitates earlier hospital
      discharge.

PMID- 19088936
TI  - Factors affecting outcome after Frey procedure for chronic pancreatitis.
AB  - BACKGROUND: Debilitating abdominal pain remains the most common presentation of
      chronic pancreatitis and the treatment remains challenging. OBJECTIVE: This
      prospective study analyzed the outcome of Frey's procedure in patients with
      inflammatory head mass. METHODS: For the period between 2002 and 2007, 77
      patients with chronic pancreatitis underwent Frey procedure for intractable
      abdominal pain. The mean follow-up was 14 months. For the purpose of analysis of
      the outcome, patients were grouped as poor pain control (19%) and good pain
      control groups (81%) based on the pain scores during follow-up. RESULTS: There
      was no 30-day mortality. The logistic regression analysis showed that decreased
      volume percentage (48%) of head mass resected (p=0.003) and small diameter of the
      pancreatic duct (p=0.05) were associated with poor pain outcome. Subgroup
      analysis revealed that patients with small duct disease were associated with
      increased operative time (p=0.001), poor pain scores (p=0.001), and increased
      weight loss (p=0.003) during follow-up. CONCLUSIONS: Frey procedure can be
      performed with zero mortality and low morbidity in a high-volume center. It
      provides good pain relief in majority of the patients. Volume of the head mass
      cored affects pain outcome. Correlation between poor results in terms of pain
      relief and weight loss following Frey's procedure, and small duct disease
      supports the view that duct diameter is an important predictor of pain relief.

PMID- 19088937
TI  - Accuracy of CT in predicting malignant potential of cystic pancreatic neoplasms.
AB  - BACKGROUND: Cystic lesions of the pancreas are being identified more frequently.
      Deciding which asymptomatic lesions can be safely followed with serial imaging
      and which require resection due to malignant potential is an increasingly common
      question. Current clinical practice is to rely on characteristics of the lesions
      on CT scan, and additional information from endoscopic ultrasound with fine
      needle aspiration (EUS-FNA) and cyst fluid analysis or endoscopic retrograde
      pancreatography (ERCP) to assess malignant potential. HYPOTHESIS: The malignant
      potential of pancreatic cystic lesions cannot be accurately predicted by CT scan.
      METHODS: CT scans from 48 patients with cystic lesions of the pancreas were
      stripped of patient identifiers and retrospectively presented to two expert
      radiologists. The radiologists recorded specific characteristics of the lesions
      thought to be important in the differential diagnosis and their opinion of the
      likely diagnosis. Diagnostic accuracy was assessed by comparing the radiologists'
      diagnoses to the final pathologic diagnosis after resection. To determine if
      clinical history, EUS-FNA or ERCP findings improved diagnostic accuracy, medical
      records were retrospectively reviewed and scored as either supporting or not
      supporting malignant potential of the lesion. RESULTS: Specific diagnoses based
      on CT findings alone were correct in an average of 39% of the cases. Even when
      diagnoses were dichotomized as benign (43%) or potentially malignant (57%,
      papillary mucinous neoplasms, mucinous cystic neoplasms, cancer), determinations
      based on CT alone were accurate in an average of 61% of cases. Accuracy rates
      were 60.4 and 62.5% for the two radiologists, although there was only fair
      agreement between them (Kappa=0.28, 95% CI=(0.01-0.55), p=0.05). When all
      clinical information available was considered together as a single dichotomous
      indicator of malignant potential, the indicator was accurate in 90% of the cases
      (Kappa=0.73, 95% CI=(0.51-0.95, p<0.0001)). CONCLUSION: Specific preoperative
      diagnosis of pancreatic cystic neoplasms by CT alone is substantially inaccurate.
      Complementary tests such as EUS-FNA with fluid analysis and ERCP should be
      recommended to improve diagnosis especially if nonoperative treatment is planned.

PMID- 19088938
TI  - Middle segment pancreatectomy can be safely incorporated into a pancreatic
      surgeon's clinical practice.
AB  - Middle segment pancreatectomy (MSP) is a new operation where the advantages of
      parenchymal preservation are counterbalanced by a high postoperative complication
      rate and unease among surgeons with adopting a new technique. This study reviews
      our experience incorporating MSP into our clinical practice focusing on the
      initial 34 consecutive patients operated on by one surgeon at a single
      institution between 1998 and 2007. Patients were divided into early (initial 17
      operations) and late (subsequent 17 operations) groups for analysis. Thirty-one
      reconstructions were by Roux-en-y pancreaticojejunostomy and three were by
      pancreaticogastrostomy. Using multiple linear regression and logistic regression,
      we found no significant differences in performance outcomes (operative time,
      blood loss, tumor size, margin negative resection rate, pancreatic fistula rate,
      hospital length of stay, postoperative complications, and hospital readmission
      rate) between our early and late experience even after adjusting for potential
      confounding variables (patient demographics, co-morbidities, neoplasm,
      pancreatitis). The pancreatic fistula rate in this series was 29.4% (10/34) and
      they were all International Study Group on Pancreatic Fistula (ISGPF) Grade A
      (60%) or B (40%). In summary, MSP is an operation with a flat learning curve and
      acceptable morbidity rate that can be safely incorporated as a parenchymal
      preserving option by pancreatic surgeons in their clinical practice.

PMID- 19088939
TI  - Surgery for secondary tumors of the pancreas.
AB  - BACKGROUND: The majority of pancreatic tumors are primary. The pancreas can
      however be the site of metastasis from renal cell cancer, lung, colon and breast
      cancers. The value of surgical treatment is unclear in such situations. The aim
      of this study was to evaluate the outcome of surgical therapy in patients with
      isolated metastases to the pancreas. METHODS: All patients who underwent
      pancreatic surgery for malignant disease from 1999 to 2005 (n=338) at the
      department of hepatobiliary and pancreatic surgery, the Royal London Hospital,
      London, were evaluated from a retrospective pancreatic database. Five patients
      had metastatic pancreatic cancer. Surgical outcome and survival were examined in
      this subset of patients. RESULTS: The primary cancer was renal cell carcinoma
      (n=2), breast (n=1), colon (n=1) and ovarian (n=1). The two patients with renal
      cell carcinoma developed pancreatic metastases years from the primary diagnosis.
      Both patients are alive 56 and 36 months post surgery. Two patients with breast
      and ovarian primary presented years after diagnosis of the primary but had
      advanced unresectable disease. There was one patient with colonic primary and
      synchronous pancreatic metastasis, and had a colectomy and Whipple's operation,
      and is alive 64 months postoperatively. CONCLUSION: The pancreas is an uncommon
      site for metastasis. Patients can present years after the treatment of primary.
      Long-term survival can be achieved with pancreatic resection in a highly selected
      subset of patients, and patients with primary renal cell carcinoma seem to have a
      favorable prognosis.

PMID- 19088940
TI  - Validation of a prognostic nomogram in patients undergoing resection for
      pancreatic ductal adenocarcinoma in a UK tertiary referral centre.
AB  - INTRODUCTION: Survival following resection for pancreatic ductal adenocarcinoma
      (PDAC) remains poor. The aim of this study was to validate a survival nomogram
      designed at the Memorial Sloan-Kettering Cancer Centre (MSKCC) in a UK tertiary
      referral centre. METHODS: Patients who underwent resection for PDAC between 1995
      and 2005 were analysed retrospectively. Standard prognostic factors and nomogram
      specific data were collected. Continuous data are presented as median (inter
      quartile range). RESULTS: Sixty-three patients were analysed. The median survival
      was 326 (209-680) days. On univariate analysis lymph node status (node +ve 297
      (194-471) days versus node -ve 367 (308-1060) days, p=0.005) and posterior margin
      involvement (margin +ve 210 (146-443) days versus margin -ve 355 (265-835) days,
      p=0.024) were predictors of a poor survival. Only lymph node positivity was
      significant on multivariate analysis (p=0.006). The median nomogram score was 217
      (198-236). A nomogram score of 113-217 predicted a median survival of 367 (295
      847) days compared to 265 (157-443) days for a score of 218-269, p=0.012.
      CONCLUSION: Increasing nomogram score was associated with poorer survival.
      However the accuracy demonstrated by MSKCC could not be replicated in the current
      cohort of patients and may reflect differences in patient demographics, accuracy
      of pathological staging and differences in treatment regimens between the two
      centres.

PMID- 19088941
TI  - Centralization of surgery: is it applicable to less populous nations?
AB  - The practice of surgery has witnessed substantial evolution over the recent
      years, especially with significant advancements in the field of medical
      diagnostics and surgical therapies. Establishment of specialized and super
      specialized surgical centers has resulted in concentrated distribution of patient
      caseload. There is an immense thrust towards the centralization of surgery
      particularly for complex high-risk procedures in the Western World. However, such
      concepts may not apply to less populous nations, and the adoption of healthcare
      delivery system of specialized centers by low-volume hospitals may produce
      overall better outcomes.

PMID- 19088943
TI  - Automated measurement of intestinal mucosa electrical parameters using a new
      digital clamp.
AB  - Electrophysiological studies that include measurements of the electrical
      parameters of the epithelium offer insight into the cell's ability to react to
      different biological effectors and their functional viability. These parameters
      are commonly measured using a Ussing permeation chamber; however, most Ussing
      permeation chambers currently available must follow a strict operational
      protocol, and the type of electrodes used has to be taken into special
      consideration. The purpose of this study was to develop a new Ussing permeation
      chamber device with an automatic digital clamp which uses a microcontroller.
      Conventional electrodes, such as platinum or Ag/AgCl electrodes, are replaced by
      stainless steel 316L working electrodes. The electrode-electrolyte interface
      (inox-Ringer's) study was performed by impedance spectroscopy in the range of 1
      10 kHz. The determination of Warburg's model electrical parameters was inferred
      from the Nyquist diagram. The model validation of the new digital clamp was
      performed experimentally on isolated segments of mouse jejunum. Two main study
      results should be mentioned. One is that impedance spectroscopy on stainless
      steel electrodes has provided Warburg's parameters, allowing the development of a
      transfer function model. The other is that the new digital clamp can
      simultaneously measure or calculate conductance, potential difference and short
      circuit current. These results have also confirmed the great importance of
      Warburg's model for determining the electrical parameters of the electrode
      electrolyte interface, and have shown that the measurement of intestinal mucosa
      electrical parameters can be achieved with a digital correction. Finally, the
      results suggest that stainless steel electrodes can be used successfully in a
      Ussing permeation chamber as working electrodes.

PMID- 19088944
TI  - Protective effect of different parts of Cassia fistula on human umbilical vein
      endothelial cells against glycated protein-induced toxicity in vitro.
AB  - The protective effect of methanol extracts of Cassia fistula (flowers, leaves and
      bark) was examined in vitro in human umbilical vein endothelial cells (HUVEC)
      against toxicity induced by glycated protein (GFBS) in vitro. The experiments
      consisted of eight groups of HUVEC with five flasks in each group. Group I was
      treated with 15% FBS, group II with GFBS (70 microM) alone, and the other six
      groups were treated with GFBS plus 25 and 50 microg of each of the three types of
      C. fistula extracts. After 72 h of incubation, cells were collected and tested
      for lipid peroxidation, antioxidant enzyme activities and glutathione S
      transferase (GST). The protective effect of C. fistula extracts against GFBS
      induced cytotoxicity was examined in HUVEC by using trypan blue exclusion and MTT
      assays. Results showed that HUVEC incubated with GFBS alone showed a significant
      (P < 0.001) elevation of lipid peroxidation accompanied by depletion of
      superoxide dismutase (SOD), catalase, glutathione peroxidase (GPx) and
      glutathione reductase (GR), in addition to decreased cytosolic GST. Treatment of
      HUVEC with C. fistula extracts at a concentration of 25 and 50 microg
      significantly decreased lipid peroxidation and normalized the activities of the
      antioxidant enzymes and GST levels in a concentration-dependent manner.
      Morphological changes of HUVEC were compared with respective controls; in
      addition, the C. fistula extracts increased the viability of HUVEC damaged by
      GFBS. A protective effect of C. fistula extracts on HUVEC against GFBS-induced
      toxicity suggested a potential beneficial effect of the extract in preventing
      diabetic angiopathies.

PMID- 19088945
TI  - Behavioral pharmacological properties after recovery from the loss of righting
      reflex induced by benzodiazepine receptor agonists in mice.
AB  - In this study we examined the behavioral pharmacological side effects after
      recovery from the loss of righting reflex induced by three benzodiazepine
      receptor agonists - zolpidem, brotizolam and flunitrazepam - in ddY mice. All
      agents caused marked motor incoordination in the rotarod test and muscle
      flaccidity in the traction test until 15 min after recovery of righting reflex.
      Thereafter, the short-acting hypnotics zolpidem and brotizolam showed a faster
      recovery than the long-acting benzodiazepine flunitrazepam. However, head twitch
      responses were observed in the mice treated with flunitrazepam, but zolpidem and
      brotizolam had no such effect. The flunitrazepam-induced head twitch response was
      antagonized by ketanserin, a 5- HT(2A) receptor antagonist. These results
      indicate that flunitrazepam, a long-acting benzodiazepine that is nonselective
      for type I and II benzodiazepine receptors, induces head twitch responses with
      muscle flaccidity after recovery from the loss of righting reflex caused by these
      drugs. In addition, these findings suggest the involvement of a 5-HT(2A)-GABA(A)
      receptor/benzodiazepine interaction in this phenomenon.

PMID- 19088946
TI  - Regulation of retinal morphology and posterior segment amino acids by 8
      isoprostaglandin E2 in bovine eyes ex vivo.
AB  - There is evidence that isoprostanes (IsoPs) can regulate exogenously applied
      excitatory amino acid neurotransmitters in bovine retina in vitro. However, the
      regulation of retinal morphology and endogenous neurotransmitter levels by IsoPs
      is unknown. We examined the effects of intravitreally injected 8-iso-PGE(2) on
      retinal tissue integrity and viability and amino acid neurotransmitters in bovine
      eye organ culture ex vivo. Exposure of bovine eyeballs to simulated experimental
      conditions revealed no retinal apoptosis and necrosis in TUNEL and DAPI staining
      and hematoxylin and eosin staining assays, respectively, and no changes in basal
      levels of amino acids in retina and vitreous humor. Furthermore, intravitreal
      injection of 8-iso-PGE(2) into bovine eyeballs had no effect on retinal apoptosis
      and integrity. Interestingly, 8-iso-PGE(2) caused a concentration-dependent
      attenuation of retinal glutamate and its metabolite glutamine and glycine levels,
      while GABA was unaffected. 8-Iso-PGE(2) (1 and 100 microM) significantly (P <
      0.001) attenuated glutamate levels by 33.9% and 48.0%, respectively. 8-Iso-PGE(2)
      (100 microM) inhibited (P < 0.01) retinal glutamine and glycine levels by 37.7%
      and 35.5%, respectively. The IsoP exhibited no effect on vitreous humor glutamine
      and glycine levels, while glutamate and GABA were not detected. Thus, 8-iso
      PGE(2) can regulate retinal amino acids without inducing cell death in bovine
      retina ex vivo.

PMID- 19088947
TI  - The role of the antioxidants lycopene and vitamin E in the prevention of
      halothane-induced hepatotoxicity.
AB  - The aim of this study was to examine the effects of lycopene and vitamin E on
      halothane-induced hepatotoxicity. Thirty-five male albino Wistar rats were
      studied. The control group (group C) did not receive any treatment. Rats in group
      H were exposed to 1.5% halothane (in 50% oxygen/50% air) for 2 h on days 10 and
      13. Group L received 25 mg/kg/day lycopene, group E received 100 IU/kg/day
      vitamin E and group LE received lycopene and vitamin E for 13 days. Similar to
      group H, groups L, E and LE were exposed to halothane. Total antioxidant capacity
      (TAC), total oxidant level (TOL) and sulfhydryl=thiol groups (SH) were measured.
      Histopathological examinations were carried out using light microscopy, and
      histopathological findings were graded on a scale of 0-6. There were no
      significant differences among the groups in TAC, TOL and SH values (P > 0.05).
      Liver injury was observed in the four treatment groups; the mean degree of damage
      was more severe in group H compared to groups E, L and LE: 2.14 +/- 0.37, 1.50 +/
      0.54, 0.85 +/- 0.69 and 0.83 +/- 0.75, respectively. This study found that both
      lycopene and vitamin E reduce halothane-induced hepatotoxicity, although the
      effect of vitamin E was not statistically significant.

PMID- 19088948
TI  - Ivabradine: pharmacodynamic aspects of its clinical use.
AB  - Ivabradine has been approved as a heart rate-lowering agent for use in the
      treatment of chronic stable angina pectoris in case of contraindication or
      intolerance to beta-blockers. This drug effectively lowers the heart rate by
      inhibiting the pacemaker current I(f) in the sinoatrial node. It appears to
      induce fewer adverse reactions than other drugs used for reducing the heart rate,
      such as calcium channel blockers or beta-blockers. Because of this favorable
      profile, ivabradine could become the first-choice drug when pure heart rate
      lowering is the therapeutic goal. This review evaluates experimental and
      preclinical data to investigate the possibilities, as well as the limitations, of
      the clinical use of ivabradine. In experimental studies, it has been shown that
      ivabradine does have some unfavorable pharmacodynamic properties, such as the
      block of all four hyperpolarization-activated cyclic nucleotide-gated channels
      and block of other ion channels at high concentrations. Clinical studies,
      however, indicate that those properties do not result in clinical consequences as
      long as ivabradine is given at the recommended dose and contraindications are
      strictly observed.

PMID- 19088949
TI  - Gateways to clinical trials.
AB  - Gateways to clinical trials is a guide to the most recent trials in current
      literature and congresses. The data in the following tables has been retrieved
      from the Clinical Trials Knowledge Area of Prous Science Integrity(R), the drug
      discovery and development portal, http://integrity.prous.com. This issue focuses
      on the following selection of drugs: (+)-Dapoxetine hydrochloride, (S)
      Tenatoprazole sodium salt monohydrate 19-28z, Acotiamide hydrochloride hydrate,
      ADV-TK, AE-37, Aflibercept, Albinterferon alfa-2b, Aliskiren fumarate, Asenapine
      maleate, Axitinib; Bavituximab, Becatecarin, beta-1,3/1,6-Glucan, Bevacizumab,
      Bremelanotide; Calcipotriol/betamethasone dipropionate, Casopitant mesylate,
      Catumaxomab, CDX-110, Cediranib, CMD-193, Cositecan; Darinaparsin, Denosumab, DP
      b99, Duloxetine hydrochloride; E75, Ecogramostim, Elacytarabine, EMD-273063,
      EndoTAG-1, Enzastaurin hydrochloride, Eplerenone, Eribulin mesilate, Esomeprazole
      magnesium, Etravirine, Everolimus, Ezetimibe; Faropenem daloxate, Febuxostat,
      Fenretinide; Ghrelin (human); I-131 ch-TNT-1/B, I-131-3F8, Iclaprim, Iguratimod,
      Iloperidone, Imatinib mesylate, Inalimarev/Falimarev, Indacaterol, Ipilimumab,
      Iratumumab, Ispinesib mesylate, Ixabepilone; Lapatinib ditosylate, Laquinimod
      sodium, Larotaxel dehydrate, Linezolid, LOR-2040; Mapatumumab, MKC-1, Motesanib
      diphosphate, Mycophenolic acid sodium salt; NK-012; Olanzapine pamoate, Oncolytic
      HSV, Ortataxel; Paclitaxel nanoparticles, Paclitaxel poliglumex, Paliperidone
      palmitate, Panitumumab, Patupilone, PCV-9, Pegfilgrastim, Peginterferon alfa-2a,
      Peginterferon alfa-2b, Pertuzumab, Picoplatin, Pimavanserin tartrate,
      Pimecrolimus, Plerixafor hydrochloride, PM-02734, Poly I:CLC, PR1, Prasugrel,
      Pregabalin, Progesterone caproate, Prucalopride, Pumosetrag hydrochloride; RAV
      12, RB-006, RB-007, Recombinant human erythropoietin alfa, Rimonabant,
      Romidepsin; SAR-109659, Satraplatin, Sodium butyrate; Tadalafil, Talampanel,
      Tanespimycin, Tarenflurbil, Tariquidar, Taurine, Tecovirimat, Telatinib,
      Telavancin hydrochloride, Telcagepant, Terameprocol, Tesofensine, Tetrodotoxin,
      Tezampanel, Tipifarnib, TPI-287, Tremelimumab; Valspodar, Vatalanib succinate,
      VCL-CB01, vCP1452, Vorinostat; XL-228; Ziprasidone hydrochloride.

PMID- 19088950
TI  - The dentist in society part 1: who are we?

PMID- 19088951
TI  - Orthodontic extrusion with magnets: a case report.
AB  - Subgingival crown-root fractures often present clinical problems when a
      restorative coverage of the fracture line conflicts with the biological width.
      Accepted treatment options include the extrusion of the remaining root with a
      conventional orthodontic appliance, surgical crown lengthening of the root, or
      root extraction with prosthetic tooth replacement. After considering esthetics
      and function, orthodontic extrusion with magnets might also be a viable
      alternative. In this report, a simplified method of orthodontic extrusion with
      magnets is presented.

PMID- 19088952
TI  - Gingival crevicular fluid levels of aspartate aminotransferase and alpha2
      macroglobulin before and after topical application of metronidazole or scaling
      and root planing.
AB  - OBJECTIVE: The aim of this study was to compare the influence of topical
      metronidazole gel application and scaling and root planing on gingival crevicular
      fluid variables. METHOD AND MATERIALS: In a split-mouth study, 39 volunteers with
      chronic periodontitis were treated by metronidazole gel or scaling and root
      planing. Clinical attachment level and probing depth were recorded, and aspartate
      aminotransferase (AST) and total/transformed Alpha2-macroglobulin were determined
      in the gingival crevicular fluid at baseline, as well as after 3 and 6 months.
      RESULTS: Both treatment procedures resulted in a gain of clinical attachment-0.67
      mm for metronidazole and 0.50 mm for scaling and root planing (P< .001)-at the
      end of the study. The median probing depth was significantly reduced by 0.66 mm
      for metronidazole and 1.00 mm for scaling and root planing (P< .001) after 6
      months. No change of AST was found. Alpha2-macroglobulin was significantly
      reduced for scaling and root planing and metronidazole after 3 and 6 months (P<
      .001). No significant difference was found between the 2 procedures at any
      variable. CONCLUSIONS: These data suggest that Alpha2-macroglobulin reflects
      clinical changes better than AST and that metronidazole and scaling and root
      planing have the same influence on clinical outcome and biochemical variables in
      the gingival crevicular fluid.

PMID- 19088953
TI  - A randomized CIE L*a*b* evaluation of external bleaching therapy effects on
      fluorotic enamel stains.
AB  - OBJECTIVE: To evaluate the effect of external bleaching on the color and
      luminosity of fluorotic stains and adjacent, normally mineralized enamel areas by
      means of CIE L*a*b* colorimetry. METHOD AND MATERIALS: Eighteen adolescents with
      mild to moderate fluorotic stains were randomly assigned to either bleaching
      group A (n = 9) or control group B. Eligibility criteria were fluorotic stained
      maxillary incisors or canines and the informed consent of the participants and
      their guardians. Using a colorimeter, CIE L*a*b* values of maxillary incisors and
      canines were assessed at baseline (T1) in the center of the fluorotic stained
      area (F1) and at adjacent, normally mineralized enamel areas (F2). Then, external
      bleaching with Illumine office (30% hydrogen peroxide, Dentsply DeTrey) was
      performed for 60 minutes, followed by color reassessment (T2). After 14 days
      (T3), a 2-week home bleaching period with a daily bleaching time of 1 hour with
      Illumine home (15% carbamide peroxide, Dentsply DeTrey) was conducted with
      subsequent color determination (T4). RESULTS: After completion of bleaching
      therapy, 96.0% of all fluorotic areas (F1) and 100% of normal enamel areas (F2)
      showed a significant change within group A, compared to 29.4% in control group B.
      Comparing the collective DeltaE (L*, a*, b*) of F1 and F2, 60.0% of all areas
      showed significant differences after completion of bleaching therapy, compared to
      88.0% initially. Of group B sites, 82.4% showed color differences in the
      beginning (T1) and 88.2% at the end (T4). CONCLUSION: Whereas a single 1-hour
      session of in-office bleaching with 30% hydrogen peroxide does not significantly
      affect the color and luminosity of fluorotic teeth, a 14-day period of home
      bleaching leads to an assimilation of the color of the fluorotic stain with the
      color of surrounding enamel areas due to different responses of sound and
      fluorotic enamel to the bleaching regime.

PMID- 19088954
TI  - Chronic sinusitis associated with the use of unrecognized bone substitute: a case
      report.
AB  - Bone grafts are used for bone augmentation to ensure optimal implant placement.
      However, this procedure may sometimes cause sinusitis. The case of a 44-year-old
      woman with the diagnosis of recurrent and chronic sinusitis of her right
      maxillary sinus with a history of dental implant surgery is presented. After
      several attempts with normal standard sinusitis therapy, unrecognized bone
      substitute was removed from the sinus cavity, which finally led to resolution of
      the sinusitis. This case reiterates the importance of a careful examination,
      consultation, and second opinion for the selection of optimal treatment.

PMID- 19088955
TI  - Six-year clinical evaluation of ceramic inlays and onlays.
AB  - OBJECTIVE: The clinical performance of IPS Empress (Ivoclar Vivadent) inlays and
      onlays was evaluated at 6 years. METHOD AND MATERIALS: Sixty-four porcelain
      inlays and onlays were placed in 29 patients, aged 21 to 70 years, by a single
      operator using the same clinical procedure. The restorations were examined for
      fracture rate; esthetics; patient acceptance; and marginal integrity, including
      caries, marginal discoloration, and gingival tolerance. All restorations were
      evaluated at the time of placement and at 1, 2, 4, and 6 years after placement.
      RESULTS: At 6 years, 93.7% of the restorations were judged clinically acceptable.
      The fracture rate was very low (3.1%), patient satisfaction was encouraging, and
      the maintenance of esthetics was superior. However, marginal discoloration and
      integrity appeared to deteriorate with time, because of loss of marginal seal and
      dissolution of the luting agent. CONCLUSION: IPS Empress ceramic inlays and
      onlays are clinically acceptable. However, a disadvantage is the dissolution of
      the resin matrix of composite resins in oral fluids.

PMID- 19088956
TI  - Marginal adaptation of Class 2 adhesive restorations.
AB  - OBJECTIVE: Control of microleakage represents a challenge for posterior composite
      restorations. The technique for composite placement may reduce microleakage. The
      null hypothesis of this in vitro study was that centripetal incremental insertion
      of composite resin would result in less microleakage than that obtained with the
      oblique incremental technique or bulk technique. METHOD AND MATERIALS:
      Standardized Class 2 preparations were made in 60 caries-free extracted third
      molars and randomly assigned to 3 groups (n = 20): (1) oblique incremental
      insertion technique (control), (2) centripetal incremental insertion technique,
      and (3) bulk insertion. The teeth were restored with a total-etch adhesive and
      microhybrid composite resin. The specimens were isolated with nail varnish except
      for a 2-mm-wide area around the restoration and then thermocycled (1,000 thermal
      cycles, 5 degrees C/55 degrees C; 30-second dwell time). The specimens were
      immersed in an aqueous solution of 50% silver nitrate for 24 hours, followed by 8
      hours of immersion in a photo-developing solution and subsequently evaluated for
      leakage. The microleakage scores (0 to 4) obtained from the occlusal and cervical
      walls were analyzed with median nonparametric tests (P < .05). RESULTS: The null
      hypothesis was rejected. All techniques attained statistically similar dentin
      microleakage scores (P = .15). The centripetal insertion technique displayed
      significantly less microleakage than the oblique technique at the enamel margins
      (P = .04). CONCLUSION: None of the techniques eliminated marginal microleakage in
      Class 2 preparations. However, in occlusal areas, the centripetal technique
      performed significantly better than the other techniques.

PMID- 19088957
TI  - Rehabilitation of an edentulous mandible with an implant-supported fixed
      prosthesis using an all-ceramic framework: a case report.
AB  - This clinical report describes the rehabilitation of an edentulous mandible with
      an implant-supported fixed prosthesis using an all-ceramic framework fabricated
      from zirconium oxide. Four interforaminal implants were inserted and allowed to
      heal submerged. The implant-supported fixed prosthesis was then fabricated using
      CAD/CAM and electroforming technology. No clinical complications were observed at
      the 6-month follow-up examination, and the patient was highly satisfied with
      function and esthetics. All-ceramic frameworks provide a high standard of
      esthetics; reduce the number of metals used in the oral cavity; and have a lower
      density compared to metals, which reduces weight in the case of large frameworks.

PMID- 19088958
TI  - Resin-dentin interfacial morphology and shear bond strengths to primary dentin
      after long-term water storage: an in vitro study.
AB  - OBJECTIVE: To evaluate the resin-dentin interfacial morphology and shear bond
      strength of several new dentin bonding systems on deep dentin of primary teeth
      after a 1-year storage period. METHOD AND MATERIALS: Test specimens were prepared
      using 5 adhesive systems (Syntac Single-Component [Ivoclar Vivadent], Prime And
      Bond NT [Dentsply DeTrey], Adper Prompt L-Pop [3M ESPE], Gluma One Bond [Heraeus
      Kulzer], and iBond [Heraeus Kulzer]) on primary deep dentin. The shear bond
      strength data were evaluated with Kruskal-Wallis and Mann-Whitney U tests.
      Debonding surfaces were examined with stereo-microscope and scanning electron
      microscopy (SEM). RESULTS: The 1-day shear bond strength test values were,
      respectively, Adper Prompt L-Pop > iBond > Prime And Bond NT > Gluma One Bond >
      Syntac Single-Component, with the differences between Prompt L-Pop and Syntac (U
      = 10, P = .006), Prompt L-Pop and Gluma (U = 7, P = .002), and Adper Prompt L-Pop
      and iBond (U = 16, P = .03) being statistically significant. The 365-day shear
      bond strength values were, respectively, Adper Prompt L-Pop > Prime And Bond NT >
      iBond > Syntac Single-Component > Gluma One Bond, with the differences between
      Adper Prompt L-Pop and Syntac (U = 0, P = .000), Adper Prompt L-Pop and Gluma (U
      = 1, P = .000), and Adper Prompt L-Pop and iBond (U = 13, P = .01) being
      statistically significant. The differences between the 1-day and 365-day subgroup
      values of Syntac (U = 18; P = .05) and Gluma (U = 1, P = .000) were statistically
      significant. Almost all specimens showed adhesive failure at stereoptical
      examination (P > .05), with the presence of resin remnants and tags on dentin and
      dentinlike remnants on resin surfaces at SEM. CONCLUSION: Syntac and Gluma group
      values decreased with aging. The best values were obtained with both Adper Prompt
      L-Pop groups.

PMID- 19088959
TI  - Osteosarcoma as a second neoplasm after chemotherapeutic treatment of hereditary
      retinoblastoma: a case report.
AB  - Osteosarcoma is the most common second neoplasm in patients with retinoblastoma.
      The risk of occurrence of second neoplasm after retinoblastoma increases after
      radiotherapy and chemotherapy. A case is presented of an 11-year-old girl who had
      painless swelling on the left side of her face for 8 days. The patient was
      asymptomatic before the onset of the swelling. Biopsy of the lesion revealed
      tumor cells forming trabeculae of osteoid and woven bone interspersed with myxoid
      and cartilaginous areas. The tumor cells showed pleomorphism and hyperchromatism
      with increased and abnormal mitotic figures consistent with the diagnosis of
      osteosarcoma. Further investigations revealed no history of retinoblastoma in the
      family. (This case was considered hereditary, however, because of the occurrence
      of the second neoplasm.) To the best of our knowledge, this is the first case of
      mandibular osteosarcoma occurring after unilateral retinoblastoma treated with
      chemotherapy.

PMID- 19088960
TI  - Living healthy on a dying planet.

PMID- 19088961
TI  - Single nanowire photovoltaics.
AB  - This tutorial review focuses on recent work addressing the properties and
      potential of semiconductor nanowires as building blocks for photovoltaic devices
      based on investigations at the single nanowire level. Two central nanowire motifs
      involving p-i-n dopant modulation in axial and coaxial geometries serve as
      platforms for fundamental studies. Research illustrating the synthesis of these
      structural motifs will be reviewed first, followed by an examination of recent
      studies of single axial and coaxial p-i-n silicon nanowire solar cells. Finally,
      challenges and opportunities for improving efficiency enabled by controlled
      synthesis of more complex nanowire structures will be discussed, as will their
      potential applications as power sources for emerging nanoelectronic devices.

PMID- 19088962
TI  - Biology and technology for photochemical fuel production.
AB  - Sunlight is the ultimate energy source for the vast majority of life on Earth,
      and organisms have evolved elegant machinery for energy capture and utilization.
      Solar energy, whether converted to wind, rain, biomass or fossil fuels, is also
      the primary energy source for human-engineered energy transduction systems. This
      tutorial review draws parallels between biological and technological energy
      systems. Aspects of biology that might be advantageously incorporated into
      emerging technologies are highlighted, as well as ways in which technology might
      improve upon the principles found in biological systems. Emphasis is placed upon
      artificial photosynthesis, as well as the use of protonmotive force in biology.

PMID- 19088963
TI  - Dynamic electrochemical investigations of hydrogen oxidation and production by
      enzymes and implications for future technology.
AB  - This tutorial review describes studies of hydrogen production and oxidation by
      biological catalysts--metalloenzymes known as hydrogenases--attached to
      electrodes. It explains how the electrocatalytic properties of hydrogenases are
      studied using specialised electrochemical techniques and how the data are
      interpreted to allow assessments of catalytic rates and performance under
      different conditions, including the presence of O2, CO and H2S. It concludes by
      drawing some comparisons between the enzyme active sites and platinum catalysts
      and describing some novel proof-of-concept applications that demonstrate the high
      activities and selectivities of these 'alternative' catalysts for promoting H2 as
      a fuel.

PMID- 19088965
TI  - The roles of the first and second coordination spheres in the design of molecular
      catalysts for H2 production and oxidation.
AB  - This tutorial review describes the development of discrete transition metal
      complexes as electrocatalysts for H2 formation and oxidation. The approach
      involves the study of thermodynamic properties of metal hydride intermediates and
      the design of ligands that incorporate proton relays. The work is inspired by
      structural features of the H2ase enzymes and should be of interest to researchers
      in the areas of biomimetic chemistry as well as catalyst design and hydrogen
      utilization.

PMID- 19088964
TI  - Photobiological hydrogen-producing systems.
AB  - Hydrogen photoproduction by micro-organisms combines the photosynthetic
      properties of oxygenic and non-oxygenic microbes with the activity of H2
      producing enzymes in nature: hydrogenases and nitrogenases. The overall
      efficiency of the process depends on the separate efficiencies of photosynthesis
      and enzymatic catalysis. This tutorial review discusses the biochemical pathways
      for H2 production in different organisms, barriers to be overcome, and possible
      suggestions for integrating photobiological H2 production with fermentative,
      anaerobic systems for a potentially more efficient process.

PMID- 19088966
TI  - New approaches to hydrogen storage.
AB  - The emergence of a Hydrogen Economy will require the development of new media
      capable of safely storing hydrogen in a compact and light weight package. Metal
      hydrides and complex hydrides, where hydrogen is chemically bonded to the metal
      atoms in the bulk, offer some hope of overcoming the challenges associated with
      hydrogen storage. The objective is to find a material with a high volumetric and
      gravimetric hydrogen density that can also meet the unique demands of a low
      temperature automotive fuel cell. Currently, there is considerable effort to
      develop new materials with tunable thermodynamic and kinetic properties. This
      tutorial review provides an overview of the different types of metal hydrides and
      complex hydrides being investigated for on-board (reversible) and off-board (non
      reversible) hydrogen storage along with a few new approaches to improving the
      hydrogenation-dehydrogenation properties.

PMID- 19088967
TI  - Oxidative addition of water to transition metal complexes.
AB  - Possible modes of reactivity of water with transition metal complexes are
      analysed and examples of oxidative addition of water are discussed in this
      tutorial review.

PMID- 19088968
TI  - Electrocatalytic and homogeneous approaches to conversion of CO2 to liquid fuels.
AB  - Research in the field of catalytic reduction of carbon dioxide to liquid fuels
      has grown rapidly in the past few decades. This is due to the increasing amount
      of carbon dioxide in the atmosphere and a steady climb in global fuel demand.
      This tutorial review will present much of the significant work that has been done
      in the field of electrocatalytic and homogeneous reduction of carbon dioxide over
      the past three decades. It will then extend the discussion to the important
      conclusions from previous work and recommendations for future directions to
      develop a catalytic system that will convert carbon dioxide to liquid fuels with
      high efficiencies.

PMID- 19088970
TI  - Cobalt-phosphate oxygen-evolving compound.
AB  - The utilization of solar energy on a large scale requires efficient storage.
      Solar-to-fuels has the capacity to meet large scale storage needs as demonstrated
      by natural photosynthesis. This process uses sunlight to rearrange the bonds of
      water to furnish O2 and an H2-equivalent. We present a tutorial review of our
      efforts to develop an amorphous cobalt-phosphate catalyst that oxidizes water to
      O2. The use of earth-abundant materials, operation in water at neutral pH, and
      the formation of the catalyst in situ captures functional elements of the oxygen
      evolving complex of Photosystem II.

PMID- 19088969
TI  - Small molecule mimics of hydrogenases: hydrides and redox.
AB  - This tutorial review is aimed at chemical scientists interested in understanding
      and exploiting the remarkable catalytic behavior of the hydrogenases. The key
      structural features are analyzed for the active sites of the two most important
      hydrogenases. Reactivity is emphasized, focusing on mechanism and catalysis.
      Through this analysis, gaps are identified in the synthesis of functional
      replicas of these fascinating and potentially useful enzymes.

PMID- 19088971
TI  - Photodriven heterogeneous charge transfer with transition-metal compounds
      anchored to TiO2 semiconductor surfaces.
AB  - A critical review of light-driven interfacial charge-transfer reactions of
      transition-metal compounds anchored to mesoporous, nanocrystalline TiO2 (anatase)
      thin films is described. The review highlights molecular insights into metal-to
      ligand charge transfer (MLCT) excited states, mechanisms of interfacial charge
      separation, inter- and intra-molecular electron transfer, and interfacial charge
      recombination processes that have been garnered through various spectroscopic and
      electrochemical techniques. The relevance of these processes to optimization of
      solar-energy-conversion efficiencies is discussed (483 references).

PMID- 19088972
TI  - Carbon nanotubes--electronic/electrochemical properties and application for
      nanoelectronics and photonics.
AB  - The fundamental chemical, redox, electrochemical, photoelectrochemical, optical
      and optoelectronic features of carbon nanotubes are surveyed with particular
      emphasis on the most relevant applications as electron donor/electron acceptor or
      as electron conductor/hole conductor materials, in solutions and in the solid
      state. Methods that aim at p- and n-doping as a means to favor hole or electron
      injection/transport are covered as well (critical review, 208 references).

PMID- 19088973
TI  - Photosynthetic energy conversion: natural and artificial.
AB  - Photosystem II (PSII) is the water splitting enzyme of photosynthesis. Its
      appearance during evolution dramatically changed the chemical composition of our
      planet and set in motion an unprecedented explosion in biological activity.
      Powered by sunlight, PSII supplies biology with the 'hydrogen' needed to convert
      carbon dioxide into organic molecules. The questions now are can we continue to
      exploit this photosynthetic process through increased use of biomass as an energy
      source and, more importantly, can we address the energy/CO2 problem by developing
      new photochemical technologies which mimic the natural system? (Critical review,
      82 references).

PMID- 19088974
TI  - Combinatorial approaches for the identification and optimization of oxide
      semiconductors for efficient solar photoelectrolysis.
AB  - The cost effective generation of hydrogen with sunlight via water
      photoelectrolysis is the critical breakthrough needed to transition the world to
      a renewable energy based hydrogen economy. A semiconductor based
      photoelectrolysis system may have cost advantages over using either a
      photovoltaic cell coupled to an electrolyzer or solar thermochemical cycles for
      water splitting. Unfortunately there is no known semiconducting material or
      combination of materials with the electronic properties and stability needed to
      efficiently photoelectrolyze water. Semiconducting oxides can have the required
      stability but present theoretical methods are insufficient to a priori identify
      materials with the required properties. Most likely, the discovered material will
      be a complex oxide containing many elements whereby each contributes to the
      required material properties such as light absorption across the solar spectrum,
      stability and electrocatalytic activity. The large number of possible
      multicomponent metal oxides, even if only ternary or quaternary materials are
      considered, points to the use of high-throughput combinatorial methods to
      discover and optimize candidate materials. In this critical review, we will cover
      some techniques for the combinatorial production and screening of metal oxides
      for their ability to efficiently split water with sunlight (88 references).

PMID- 19088975
TI  - Density functional theory simulations of complex hydride and carbon-based
      hydrogen storage materials.
AB  - This critical review covers the mechanisms underlying density functional theory
      (DFT) simulations and their relevance in evaluating, developing and discovering
      new materials. It is intended to be of interest for both experimentalists and
      theorists in the expanding field of hydrogen storage. We focus on the most
      studied classes of materials, metal-hydride, -amide, and -borohydride mixtures,
      and bare and transition metal-doped carbon systems and the utility of DFT
      simulations for the pre-screening of thermally destabilised reaction paths (170
      references).

PMID- 19088976
TI  - Multifunctional 3D nanoarchitectures for energy storage and conversion.
AB  - The design and fabrication of three-dimensional multifunctional architectures
      from the appropriate nanoscale building blocks, including the strategic use of
      void space and deliberate disorder as design components, permits a re-examination
      of devices that produce or store energy as discussed in this critical review. The
      appropriate electronic, ionic, and electrochemical requirements for such devices
      may now be assembled into nanoarchitectures on the bench-top through the
      synthesis of low density, ultraporous nanoarchitectures that meld high surface
      area for heterogeneous reactions with a continuous, porous network for rapid
      molecular flux. Such nanoarchitectures amplify the nature of electrified
      interfaces and challenge the standard ways in which electrochemically active
      materials are both understood and used for energy storage. An architectural
      viewpoint provides a powerful metaphor to guide chemists and materials scientists
      in the design of energy-storing nanoarchitectures that depart from the hegemony
      of periodicity and order with the promise--and demonstration--of even higher
      performance (265 references).

PMID- 19088977
TI  - Heterogeneous photocatalyst materials for water splitting.
AB  - This critical review shows the basis of photocatalytic water splitting and
      experimental points, and surveys heterogeneous photocatalyst materials for water
      splitting into H2 and O2, and H2 or O2 evolution from an aqueous solution
      containing a sacrificial reagent. Many oxides consisting of metal cations with d0
      and d10 configurations, metal (oxy)sulfide and metal (oxy)nitride photocatalysts
      have been reported, especially during the latest decade. The fruitful
      photocatalyst library gives important information on factors affecting
      photocatalytic performances and design of new materials. Photocatalytic water
      splitting and H2 evolution using abundant compounds as electron donors are
      expected to contribute to construction of a clean and simple system for solar
      hydrogen production, and a solution of global energy and environmental issues in
      the future (361 references).

PMID- 19088978
TI  - B-N compounds for chemical hydrogen storage.
AB  - Hydrogen storage for transportation applications requires high volumetric and
      gravimetric storage capacity. B-N compounds are well suited as storage materials
      due to their light weight and propensity for bearing multiple protic (N-H) and
      hydridic (B-H) hydrogens. This critical review briefly covers the various methods
      of hydrogen storage, and then concentrates on chemical hydrogen storage using B-N
      compounds. The simplest B-N compound, ammonia borane (H3NBH3), which has a
      potential 19.6 wt% hydrogen storage capacity, will be emphasised (127
      references).

PMID- 19088979
TI  - Electron spin resonance spectroscopy in drug delivery.
AB  - The finding of non-viral carriers for the delivery and release of pharmaceutical
      and biological compounds to ill organs and tissues is one of the most widely
      investigated topic in medicinal and biological chemistry in the last decades.
      Prior to being used as drug vehicles in the living organisms, all of the new
      carriers are required to be fully characterized from a physico-chemical point of
      view, with respect to stability, charge, size, mobility, etc. To this aim,
      several molecular and bulky techniques have been employed for characterization.
      This review considers the results obtained with a molecularly oriented
      spectroscopic method, i.e. electron spin resonance (ESR). The application of this
      technique in its various forms derived from continuous-wave (cw-ESR) and pulsed
      wave (pw-ESR) modes are reviewed. In particular, carriers such as liposomes
      (intended for gene therapy, boron neutron capture therapy, oxymetry, and others),
      micelles, hydrogels, nanoparticles, dendrimers, cyclodextrins and
      cucurbit[n]urils are considered.

PMID- 19088980
TI  - Improved hydrogen storage properties of a V decorated Mg nanoblade array.
AB  - An ultra-thin layer of V has been coated onto the surface of individual Mg
      nanoblades by dynamic shadowing growth. This 2.25 at% V decorated Mg nanoblade
      array can absorb and desorb hydrogen rapidly at temperatures T>or= 500 K after
      activation by one hydrogen cycle, with a low hydrogen absorption activation
      energy of 35.0+/-1.2 kJ per mol H(2) and a desorption activation energy of 65.0+/
      0.3 kJ per mol H(2). The improved hydrogen sorption kinetics is attributed to
      both the catalytic effect of the V coating and the unique nanoblade morphology
      with a large surface area and small hydrogen diffusion length.

PMID- 19088981
TI  - Stepwise walden inversion in nucleophilic substitution at phosphorus.
AB  - We have studied the mechanism of S(N)2@P reactions in the model systems X(-) +
      PMe(2)Y and X(-) + POR(2)Y (with R=Me, OH, OMe; and X, Y=Cl, OH, MeO) using
      density functional theory at OLYP/TZ2P. Our main purpose is to analyze the nature
      of the Walden inversion in our model nucleophilic substitution reactions. Walden
      inversion is well-known to proceed, in general, as a concerted umbrella motion of
      the substituents at the central atom. Interestingly, we find here that, in
      certain model reactions, Walden inversion can also proceed in a stepwise fashion
      in which the individual substituents of the umbrella flip, consecutively, from
      the educt to the product conformation via separate barriers on the reaction
      profile. We also examine how variation in nucleophile and leaving group may tune
      the pentavalent transition structure between labile transition state (TS) and
      stable transition complex (TC). Furthermore, we explore the various competing
      multistep pathways in the symmetric (X=Y) and asymmetric (X not equal Y)
      substitution reactions in our model reaction systems.

PMID- 19088982
TI  - Viscoelastic characterization of benzo-crown ether functionalized electroactive
      films.
AB  - Electrochemical, acoustic wave and imaging (AFM) methods were used to
      characterize electroactive poly[Ni(3-Mesalophen-b15-c5)] films. The distinct
      physical principles of these techniques generate different responses to film
      characteristics, such that their simplistic correlation in the context of a
      single uniform film model does not adequately describe the data. Film behaviour
      can only be rationalised using a two layer model comprising a dense (poorly
      solvated) inner layer and an outer layer comprising islands of diffuse (highly
      solvated) polymer. The two layers can be observed directly by AFM imaging. The
      balance of their contributions shifts with polymer coverage: the inner layer
      dominates thin films and the outer layer dominates thick films. The inner layer
      is acoustically more rigid and, even if ion transport is slow, is sufficiently
      thin as to pose no major barrier to electrochemical communication with the
      underlying electrode. For very thin films, gravimetric interpretation of the
      acoustic wave response correlates simply with coulometric data; thicker films
      require viscoelastic phenomena to be considered. The low polymer segment density
      of the outer layer facilitates ion transport but results in weak acoustic
      coupling, such that the acoustic and coulometric assays differ. By combining the
      AFM, acoustic wave and electrochemical responses one can establish a quantitative
      picture of component layer populations and characteristics.

PMID- 19088983
TI  - Protonation of guanine quartets and quartet stacks: insights from DFT studies.
AB  - Density functional theory methods have been used to investigate the effects of
      adding one to four protons to a one-plane guanine quartet (G4) and a two-plane
      guanine quartet stack (2G4). The singly protonated G4 complex prefers protonation
      at the Watson-Crick face of the O6 moiety. However, all multi-protonated G4
      complexes favour protonation at the Hoogsteen face of the O6 centres. The proton
      affinities have also been calculated for the addition of one, two, three and four
      protons to the central oxygens of G4 and have been compared with those of
      monomeric guanine and other biochemically appropriate bases. These results
      suggest that a G4 might reasonably readily accept two protons. For the singly to
      quadruply protonated 2G4's, the added protons prefer to distribute over both
      planes with maximally two per plane. Furthermore, unlike the (G4-nH+) n>or= 2
      complexes, protonation at the Watson-Crick faces of the O6 moieties is found to
      be preferred for all protonation states. In addition, (2G4-nH+) n=1-4 complexes
      were also obtained in which inter-plane hydrogen bonds were formed, effectively
      enabling the protons to 'sit between' planes.

PMID- 19088984
TI  - A structural and spectroscopic investigation of the hydrochlorination of 4
      benzylaniline: the interaction of anhydrous hydrogen chloride with chlorobenzene.
AB  - The hydrochlorination of 4-benzylaniline in chlorobenzene to produce 4
      benzylaniline hydrochloride has been examined. This has required spectroscopic
      and computational analysis of the solvation of gaseous HCl in the process
      solvent. The characterisation of the reagent and product of the hydrochlorination
      reaction by various techniques, including FTIR and (1)H NMR spectroscopy and X
      ray diffraction, is described. The infrared spectrum of the hydrochloride salt
      contains a strong Fermi resonance interaction, readily distinguishing it from
      that of the starting material. Using the structural results as a basis, the
      lattice energies of reagent and product have been evaluated by the recently
      developed PIXEL method. This method allows the contributions of specific
      intermolecular interactions to the total lattice energy to be assessed and, in
      this case, tentatively correlated with solubility measurements.

PMID- 19088985
TI  - Sorption induced relaxations during water diffusion in S-PEEK.
AB  - This paper presents an analysis of the sorption kinetics of water vapor and
      liquid water in the glassy polymer sulfonated poly(ether ether ketone) (S-PEEK).
      Sorption isotherms are determined experimentally using a gravimetric sorption
      balance, and the relative contributions of Fickian diffusion and relaxational
      phenomena are quantified as a function of the water concentration in the polymer
      using the model of Hopfenberg and Berens.Analysis of the sorption isotherms and
      determination of the sorption kinetics prove the occurrence of both Fickian
      sorption behavior and relaxational phenomena already at very low water
      concentrations in the polymer. With increasing water concentration, the relative
      importance of relaxation phenomena increases, whereas the relative contribution
      of Fickian diffusion decreases.Based on the water vapor sorption kinetics only,
      the Fickian diffusion coefficient increases over two orders of magnitude with
      increasing water vapor concentration. Taking also the diffusion kinetics from
      liquid water sorption experiments into account reveals a change of even three
      orders of magnitude of the Fickian diffusion coefficient when the water
      concentration in the polymer increases.

PMID- 19088986
TI  - Testing a modified model of the Poisson-Boltzmann theory that includes ion size
      effects through Monte Carlo simulations.
AB  - In this work we test the validity of a recent modified Poisson-Boltzmann (MPB)
      theory that includes ion size effects through a Langmuir-type correction. In
      particular, we will focus on an analytic charge-potential relationship accounting
      for such effects. Previous electric double layer (EDL) surveys have demonstrated
      that the inclusion of ions size in classical EDL theories, based on the Poisson
      Boltzmann (PB) equation, can yield considerable improvements. In this sense, the
      theory we analyze assumes that, as a result of the excluded volume, the ion
      concentration close to the charged surface cannot exceed a fixed value determined
      by the close packing fraction. This leads to predictions of counterion
      concentrations (in this region) smaller than the corresponding PB values. In our
      opinion, it is worthwhile to test the validity of this novel theory. To this end,
      computer simulations appear as a useful tool for this kind of task. Our results
      prove that the above-mentioned analytical expression works fairly well for 1 : 1
      electrolytes and large ions, and its predictions can be considerably improved
      with certain corrections in the estimation of some key parameters. However, it
      fails for multivalent electrolytes.

PMID- 19088987
TI  - Ultrafast intramolecular electronic energy transfer in rigidly linked
      aminopyrenyl-aminobenzanthronyl dyads--a femtosecond study.
AB  - Ultrafast electronic excitation transfer (EET) followed by structural and
      vibrational relaxation (VER) of the acceptor have been characterised using
      transient absorption and transient lens techniques.

PMID- 19088988
TI  - Counter-ion modulation of long-distance pi-bonding of the open-shell p
      benzoquinone anions.
AB  - X-Ray crystallography of dichlorodicyano- or tetrachloro-p-benzoquinone salts
      with polyether-ligated alkali metals reveals discrete supramolecular complexes:
      [{M(L)A}(2)]. They show pairs of co-facial p-benzoquinone anions (A(-)) arranged
      at close interplanar separation: r(pi) approximately 2.9 A characteristic of ion
      radical pi-dimers. Moreover, these pi-bonded anions are tethered by couples of
      alkali-metal cations (M(+)) nested in the crown-ether (L) cavities. The
      structures of such assemblies are compared to the non-tethered pi-dimers (with
      1:1 cation/anion coordination), as well as to the separated dianionic [A(2)](2-)
      and monoanionic [A(2)](-)* pi-dyads. Such a comparison reveals that, contrary to
      electrostatic implications, counter-ion coordination (or monomer charge decrease)
      is accompanied by increase of the interplanar separations (r(pi)) between pi
      bonded p-benzoquinones. In addition, counter-ion bridges switch the lateral
      monomer offset from longitudinal in the separated pi-dimers to transversal in the
      tethered assemblies. In dichloromethane, equilibrium constants of pi-dimers
      formation are higher for the ion-paired salts as compared to those of the
      separated analogues, but the enthalpies of pi-dimerization (DeltaH(D)) are
      essentially independent of counter-ions. Thus, structural (r(pi)) and
      thermodynamic (DeltaH(D)) features of the anionic p-benzoquinone pi-dimers
      suggest a superior compensation of coulombic interactions and relatively minor
      role of counter-ions in the long-distance ion-radicals pi-bonding.

PMID- 19088989
TI  - Strengthening intersubunit hydrogen bonds for enhanced stability of recombinant
      urate oxidase from Aspergillus flavus: molecular simulations and experimental
      validation.
AB  - The aim of this study was to obtain molecular insight into the deactivation of
      recombinant urate oxidase (uricase, UOX, EC 1.7.3.3) (rUOX) from Aspergillus
      flavus. The enzyme is a tunnel-shaped homotetramer and has important clinical
      applications. By means of molecular dynamics simulations, multidimensional
      structural characterization and enzyme activity assays, we concluded that the
      thermal deactivation of UOX at neutral pH was associated with the loss of
      intersubunit hydrogen (H) bonds. This mechanism could also explain the
      deactivation of dilute aqueous UOX. Thermal deactivation of aqueous UOX due to
      dissociation of its subunits was ruled out. Displacement of H(2)O from the
      surface of UOX by less polar solvents such as methanol and dimethyl sulfoxide
      (DMSO) was proposed as an approach for strengthening intersubunit H bonds and
      consequently UOX stability. The effectiveness of this method was validated by
      both in silico and in vitro experiments. The results mentioned above provide
      insights for improving the stability of UOX and extending its applications. They
      may also be helpful for understanding the properties of other multimeric
      proteins.

PMID- 19088990
TI  - Quantum mechanical study and vibrational spectra of indazolium-3-carboxylate and
      its decarboxylation product, the N-heterocyclic carbene indazol-3-ylidene.
AB  - Indazolium-3-carboxylate is a molecule that can be found as the nucleus of
      several pseudo-cross-conjugated mesomeric betaines, such as the alkaloid
      nigellicine. From a chemical point of view, one of the more interesting
      properties of this class of molecules is the possibility of forming an N
      heterocyclic carbene by thermal decarboxylation. In this paper we have studied
      the carbene generation by decarboxylation of 1,2-dimethyl indazolium-3
      carboxylate, using vibrational (infrared and Raman) spectroscopy and quantum
      chemistry calculations. Normal mode analysis allowed us to analyse the changes in
      the stretching force constants upon decarboxylation and to establish
      spectroscopic-structure relationships. We also investigate the effect of 5
      halogen (fluoro, chloro) substitution on the carbene generation. Decarboxylation
      energy profiles of the three derivatives were calculated. Crossing of the energy
      paths when going from the transition state to the final product were obtained.
      The theoretical tendency found for the activation energies agrees with that
      observed for the decarboxylation temperatures and for the calculated NICS values
      of the benzene moieties.

PMID- 19088991
TI  - Ultrafast electronic excitations of small sodium clusters and the onset of
      electron thermalization.
AB  - In this paper we report simulations of the ultrafast laser excitation and
      relaxation of the correlated valence electrons of a Na(8) cluster. The aim is
      twofold: first, while the total energy stays constant when the exciting laser
      pulse is over, we observe that the entropy computed from the reduced one electron
      density matrix rises on a much longer time scale. We discuss whether this can be
      understood as the onset of the thermalization of a finite system. Second, we
      describe this process with eight different methods of wavefunction-based
      electronic structure theory, which have been adapted for an explicitly time
      dependent description. Their respective advantages and limitations for the
      simulation of the excitation and subsequent relaxation are explained.

PMID- 19088992
TI  - Dielectric saturation of water in a membrane protein channel.
AB  - Water molecules in confined geometries like nanopores and biological ion channels
      exhibit structural and dynamical properties very different from those found in
      free solution. Protein channels that open aqueous pores through biological
      membranes provide a complex spatial and electrostatic environment that decreases
      the translational and rotational mobility of water molecules, thus altering the
      effective dielectric constant of the pore water. By using the Booth equation, we
      study the effect of the large electric field created by ionizable residues of an
      hour-glass shaped channel, the bacterial porin OmpF, on the pore water dielectric
      constant, epsilon(w). We find a space-dependent significant reduction (down to
      20) of epsilon(w) that may explain some ad hoc assumptions about the dielectric
      constant of the protein and the water pore made to reconcile model calculations
      with measurements of permeation properties and pK(a)'s of protein residues. The
      electric potential calculations based on the OmpF protein atomic structure and
      the Booth field-dependent dielectric constant show that protein dielectric
      constants ca. 10 yield good agreement with molecular dynamics simulations as well
      as permeation experiments.

PMID- 19088993
TI  - The monohydrate and dihydrate of acetic acid: a high-resolution microwave
      spectroscopic study.
AB  - High-resolution microwave spectra of the monohydrate and dihydrate of acetic acid
      were recorded using a pulsed nozzle Fourier transform microwave spectrometer. The
      rotational and centrifugal distortion constants of these species were determined,
      which confirms the structures predicted by ab initio calculations that the H(2)O
      molecules bind to the carboxylic group to form hydrogen-bonded ring complexes.
      The dependence of the intensity of the rotational transitions on the power of the
      microwave pulses suggests that both hydrates have small a-and b-dipole moments of
      less than 0.3 Debye. All rotational transitions were split into two by internal
      rotation of the methyl group. Analysis of the splitting using both the PAM and
      the CAM methods allows the orientation and the height of the three-fold barrier
      to internal rotation (V(3)) of the methyl group to be determined accurately. A
      consistently declining trend of V(3) from the acid monomer [168.16 cm(-1), B. P.
      van Eijck, J. van Opheusden, M. M. M. van Schaik and E. van Zoeren, J. Mol.
      Spectrosc., 1981, 86, 465] through the monohydrate (138.396 cm(-1)) and the
      dihydrate (118.482 cm(-1)) was observed, which suggests that the amount of
      decrease of V(3) may be correlated with the strength of hydrogen bonding in these
      complexes.

PMID- 19088994
TI  - Metal-histidine-glutamate as a regulator of enzymatic cycles: a case study of
      carbonic anhydrase.
AB  - Histidine is a very common metal ligand in metalloenzymes. Besides being an
      efficient Lewis base, its electronic properties are essential to shape the metal
      ability to catalyze the reaction. Here we show that histidine's properties can be
      tuned, in turn, by an easy proton transfer to a nearby glutamate. We study this
      situation in Human Carbonic Anhydrase II (HCA II) in which one of the three
      histidines bound to zinc (His119) interacts also with a glutamate residue
      (Glu117). Proton transfer from His119 to Glu117 has been hypothesized in the
      past, however realistic modeling is performed here for the first time. We show
      that the carboxylate group of Glu117 behaves only as a hydrogen bond acceptor in
      the hydroxy form of HCA II. On the other hand, our results suggest that Glu117
      could exist either as a hydrogen bond acceptor or as a proton acceptor in the
      aqua form of HCA II, the two isomers having almost the same thermodynamic
      stability. We propose that this proton shift may be used by the enzyme to
      facilitate the final displacement of bicarbonate by water.

PMID- 19088995
TI  - Kinetic, mechanistic and temperature dependence study of Cl reactions with
      CH3OC(O)H and CH3CH2OC(O)H. Atmospheric implications.
AB  - Reactions of Cl atoms with CH(3)OC(O)H (1) and CH(3)CH(2)OC(O)H (2) have been
      studied using the Discharge Flow-Mass Spectrometric (DF-MS) method. The study has
      been carried out at 1 Torr total pressure under pseudo-first-order conditions in
      the temperature range 253 K to 333 K to approach the tropospheric temperature
      profile. The measured room temperature rate coefficients are k(1)=(1.01+/-0.15) x
      10(-12) cm(3) molecule(-1) s(-1) and k(2)=(8.78+/-1.22) x 10(-12) cm(3) molecule(
      1) s(-1) (errors are 2sigma) and the fitted Arrhenius expressions, k(1)=(1.7+/
      1.4) x 10(-11) exp -(810+/-250)/T cm(3) molecule(-1) s(-1) and k(2)=(5.5+/-4.8) x
      10(-11) exp -(556+/-268)/T cm(3) molecule(-1) s(-1) (errors are 2sigma). The
      reactions proceed through the abstraction of an H atom to form HCl and the
      corresponding radical. At 298 K and 1 Torr, yields on HCl of 0.95+/-0.09 (error
      is 2sigma) for reaction (1) and 0.96+/-0.11 (error is 2sigma) for reaction (2)
      have been measured. The tropospheric lifetimes are calculated and discussed.

PMID- 19088996
TI  - Thermoelectric behavior of a mixed ionic electronic conductor, Ce(1-x)GdxO(2-x/2
      delta).
AB  - The thermoelectric power of a mixed ionic electronic conductor oxide Ce(1
      x)Gd(x)O(2-x/2-delta) (x=0.1) was measured as a function of oxygen activity in
      the range of -20 <or= log a(O(2)) <or= 0 at different temperatures in the range
      of 800-1100 degrees C, supposedly in two different states of the oxide with
      respect to the oxygen nonstoichiometry (delta) distribution: nabladelta=0 and
      nabladelta not equal 0. The two sets of thermopower, corresponding to these two
      different nonstoichiometry distributions, generally change their sign from
      negative to positive, as the electrical conductivity changes from ionic to
      electronic with decreasing oxygen partial pressure from 1 atm, indicating a
      change in carrier types from positive to negative carriers. The two, however,
      exhibit a significant difference in magnitude (normally up to 400 microV K(-1))
      particularly in the transition region from ionic to electronic conduction. The
      thermopower in the two different states has been described thermodynamically as a
      function of oxygen partial pressure or the electronic to ionic conductivity
      ratio. It has been found that the kinetic term A(n) of the electronic thermopower
      [as in theta(n)=(k/e)(ln N(c)/n + A(n))] takes a numerical value 2 as the
      electronic transference number approaches 1, quite contrary to the theoretically
      predicted value 0 for a small polaron conduction mechanism.

PMID- 19088997
TI  - Large static first and second hyperpolarizabilities dominated by excess electron
      transition for radical ion pair salts M2*+TCNQ*- (M=Li, Na, K).
AB  - The interesting radical ion pair salts M(2)*(+)TCNQ*(-) (M=Li, Na, K) are a
      particular class of charge transfer complexes with excess electron. The ground
      states of these complexes are triplet. The C(2v) symmetry geometrical structures
      of the M(2)*(+)TCNQ*(-) (M=Li, Na, K) with all-real frequencies are obtained at
      the density functional theory (DFT) B3LYP/6-31+G(d) level. All calculations of
      electric properties in this paper have been carried out at the restricted open
      shell second order Moller-Plesset perturbation theory (ROMP2) level. Owing to
      existing excess electron (from the polarized alkali metal atoms) these charge
      transfer complexes exhibit large nonlinear optical (NLO) responses dominated by
      excess electron transitions.For these radical ion pair salts M(2)*(+)TCNQ*(-),
      the static first hyperpolarizabilities (beta(0)) are large. The order of beta(0)
      values is 19 203 (M=Li)<24 140 (M=Na) < 29 065 a.u. (M=K). Specially, the second
      hyperpolarizability (gamma(0)) of the complexes with excess electron is obtained
      for the first time. These static second hyperpolarizabilities are also large. The
      order of gamma(0) values is 2,213,006 (M=Li)<3,136,754 (M=Na)<7,905,623 a.u. (M =
      K). Among the three structures, K(2)*(+)TCNQ*(-) has the largest gamma(0) value
      to be 7.9 x 10(6) a.u. (3982 x 10(-36) esu), which is about 9 times larger than
      that of the intramolecular charge transfer complex sigma-arylvinylidene trans
      [Ru(4-C[double bond, length as m-dash]CHC(6)H(4)C[triple bond, length as m
      dash]CC(6)H(4)NO(2))Cl(dppm)(2)]PF(6) [Hurst et al., Organometallics, 2001, 20,
      4664]. The present investigation provides a new kind of candidates for the high
      performance NLO materials.

PMID- 19088998
TI  - Kinetics of hydrogen-bond rearrangements in bulk water.
AB  - Molecular dynamics simulations are used to investigate the kinetics of hydrogen
      bond rearrangements in bulk water at ambient temperatures. Configurational
      analyses reveal three distinct bond-breaking processes, two of which constitute
      rearrangements in the hydrogen-bond network. The kinetic analyses demonstrate the
      applicability of simple first-order kinetics and reveal a large breadth of time
      scales. In agreement with experiments we find that transitions between stable
      hydrogen-bonded configurations are characterised by an unstable, transient, non
      bonded configuration. The overall rate of hydrogen-bond rearrangements is
      determined as 0.89 ps(-1) (1.12 ps), in very good agreement with experimental
      estimates.

PMID- 19088999
TI  - Formic acid electrooxidation on Bi-modified polyoriented and preferential (111)
      Pt nanoparticles.
AB  - Formic acid electrooxidation was studied on Bi modified polyoriented and
      preferential (111) Pt nanoparticles. For both types of nanoparticles, Bi coverage
      was progressively increased and its effect on formic acid electrooxidation was
      evaluated using cyclic voltammetry and chronoamperometric measurements. In both
      experiments, significant and progressive enhancements on the electrooxidation
      current densities were obtained in comparison to the bare Pt nanoparticles. In
      voltammetry, at maximum Bi coverage, higher current densities at peak potential
      were obtained with the preferential (111) Pt nanoparticles (approximately 42 mA
      cm(-2)) as compared to the polyoriented Pt nanoparticles (approximately 32 mA cm(
      2)) in agreement with previous single crystal studies. Nevertheless, this
      tendency was not observed in chronoamperometry at 0.4 V where currents obtained
      at maximum Bi coverage were similar. On the other hand, CO poison formation was
      also evaluated at open circuit potential. The resulting electrochemical activity
      has been rationalized using different parameters, such as surface structure, size
      domains, particle size and Bi coverage.

PMID- 19089000
TI  - Energetics of linear carbon chains in one-dimensional restricted environment.
AB  - The energetics of even and odd linear C(n) carbon chain clusters are investigated
      by hybrid density functional theory (DFT) calculations. These molecular species
      are especially interesting due to their recent observation inside carbon
      nanotubes by polarized resonant Raman spectroscopy and high-resolution
      transmission electron microscopy (HRTEM) by different research groups. Neutral,
      anionic and dianionic carbon chains were studied with sizes up to n=75, although
      most presented calculations are limited to n<or= 24. Aggregation into longer
      chains is favored for neutral and anionic chains of any size. The barrier to
      aggregation of 2C(n)<-->C(2n) is of the order of 40-20 kcal mol(-1), which
      gradually decreases with increasing chain size, n. These barriers can be overcome
      during the high temperature synthesis or annealing conditions, but not when
      cooled down for the HRTEM and Raman experiments. Therefore, in addition to the
      already observed long chains also shorter chains should be observable under
      appropriate conditions inside carbon nanotubes.

PMID- 19089002
TI  - Recent developments in the coordination chemistry of bis(imino)acenaphthene
      (BIAN) ligands with s- and p-block elements.
AB  - Bis(imino)acenaphthenes (BIAN) have been known for many years. However, it is
      only since the 1990s that such compounds have been recognized as robust ligands
      for the support of catalytically active transition metal centers. More recently,
      the unique stereoelectronic properties of the BIAN ligand class are beginning to
      be appreciated and exploited for some fascinating new developments in synthetic,
      structural and catalytic s- and p-block chemistry.

PMID- 19089001
TI  - DNA hydrolytic cleavage catalyzed by synthetic multinuclear metallonucleases.
AB  - Much effort has been directed at understanding the roles of metal ions in
      catalyzing the hydrolysis of phosphodiester bonds of nucleic acids. Nucleases are
      metalloenzymes that have a wide variety of active site motifs and that contain a
      variety of different metal ions. This property has made it difficult to propose a
      simple mechanism for these enzymes. Therefore, design and synthesis of metal
      complexes, which can mediate phosphodiester bond cleavage via hydrolytic
      pathways, are of important significance in elucidation of the catalytic
      mechanisms for the natural nucleases and in development of the biomacromolecule
      targeted drugs. Recent progress has extended to the design of synthetic
      multinuclear metallonucleases containing two or more Fe(III), Zn(II), Cu(II),
      Co(II/III), or Ln(III/IV) ions. The ligands in these complexes include natural
      and nonnatural organic molecules, i.e., mainly benzimidazolyl- and pyridyl-based
      organic molecules, azamacrocyclic and aminocarboxylic derivatives, and their
      conjugates to polypeptides or oligonucleotides. The purpose of this perspective
      is to highlight: (1) the differences in structure and composition between natural
      and synthetic multinuclear metallonucleases; (2) the design strategies of
      synthetic multinuclear metallonucleases; (3) the relationship between the
      structures and nucleolytic activities of synthetic multinuclear metallonucleases;
      and (4) the cooperativities between metal sites, and between metal sites and
      ligands in the courses of phospodiester linkage hydrolysis. A comparison
      illustrates unifying themes in the catalysis of phosphodiester linkage hydrolysis
      by natural and synthetic multinuclear metallonucleases. Indeed, there are
      features that converge about the chemistry that provides insight into how changes
      in metal ions and ligands of both natural and synthetic metallonucleases may lead
      to the same overall outcome of phosphodiester backbone cleavage. In addition, we
      will also discuss the solvation effect of synthetic multinuclear metallonucleases
      and the challenges that should be faced toward the development of synthetic
      multinuclear metallonucleases with DNA sequence or structure selectivity by
      applying the principles of coordination and enzymatic chemistry.

PMID- 19089003
TI  - An enantiopure N,N,S scorpionate ligand derived from (+)-camphor.
AB  - Reductive S-S bond cleavage of a disulfide precursor obtained from a pyridine
      catalyzed Peterson-type reaction starting from camphorpyrazole , thionyl chloride
      and 2-methyl-2-(methyldithio)propionaldehyde yields 2,2'-bis(camphorpyrazol-1-yl)
      2-methylpropane-2-thiol (HSiprbpm3cam, ); the first zinc complexes bearing this
      ligand exhibit kappa3 coordination of the ligand.

PMID- 19089004
TI  - Dissymmetry of an exogenous bridging ligand facilitates the assembly of a
      ferromagnetic and chiral [CuIINiII] complex.
AB  - A dissymmetric exogenous bridging ligand provides access to a heterometallic
      [NiIICuII] complex held together by a symmetric compartmental ligand; the complex
      is chiral and, as a result of ferromagnetic coupling, it exhibits an S=3/2 spin
      ground state, the EPR of which has been simulated.

PMID- 19089005
TI  - Relationship between metal-metal bond length and internal rotation in diruthenium
      tetracarboxylate paddlewheel complexes.
AB  - The Ru-Ru bond length for Ru2II,III and Ru2II,II paddlewheel complexes containing
      the bulky carboxylate ligand 2,4,6-triisopropylbenzoate was found to decrease
      despite a reduction in Ru-Ru bond order, due to increased internal rotation.

PMID- 19089006
TI  - Potential new inorganic antitumour agents from combining the anticancer
      traditional Chinese medicine (TCM) liriodenine with metal ions, and DNA binding
      studies.
AB  - Liriodenine (), an active component of the anticancer traditional Chinese
      medicine (TCM), was isolated from Zanthoxylum nitidum. Its reactions with Pt(II)
      and Ru(II) afforded three metal complexes: cis-[PtCl2(L)] (), cis
      [PtCl2(L)(DMSO)] (), and cis-[RuCl2(L)(DMSO)2].1.5H2O (), the crystal structures
      of , and were determined by single-crystal X-ray diffraction methods. These
      complexes were fully characterized by elemental analysis, IR spectrophotometry,
      1H and 13C NMR spectroscopies, and ES mass spectrometry. The in vitro
      cytotoxicity of and complexes against 11 human tumour cell lines was assayed. The
      metal-based compounds exhibit enhanced cytotoxicity vs. free , suggesting that
      these compounds display synergy in the combination of metal ions and liriodenine.
      The binding properties of and its complexes to ct-DNA were investigated through
      UV-vis, fluorescence, CD spectra, viscosity and agarose gels electrophoretic
      measurements.

PMID- 19089007
TI  - Co(II), Ni(II), Cu(II) and Zn(II) complexes of tetraphenylazadipyrromethene.
AB  - The synthesis, crystallographic and spectroscopic properties of four divalent
      isomorphous metal complexes of tetraphenylazadipyrromethene are described.

PMID- 19089008
TI  - Reversible light-induced magnetization change in an azobenzene-attached
      pyridylbenzimidazole complex of iron(II) at room temperature.
AB  - Reversible photomagnetic effects were demonstrated at room temperature by the use
      of a new iron(II) complex t100c0-[Fe()3](BF4)(2).3H2O ( =phenyl(2-pyridin-2-yl-3H
      benzoimidazol-5-yl)diazene), based on the strategy of the so-called "ligand
      driven light-induced spin change" (LD-LISC) effect. The complex showed thermal
      spin crossover in both solid and solution states, showing a transition
      temperature T1/2=279(16) K in acetone. trans-cis Photoisomerization of azobenzene
      moieties using different energy lights afforded reversible photomagnetic effects,
      which were directly determined using the Evans 1H NMR method.

PMID- 19089009
TI  - Addition of ethynylferrocene to transition-metal complexes containing a chelating
      1,2-dicarba-closo-dodecaborane-1,2-dichalcogenolate ligand--in vitro
      cooperativity of a ruthenium compound on cellular uptake of an anticancer drug.
AB  - The addition reactions of the 16e half-sandwich complexes (p-cymene)M(S2C2B10H10)
      (, M=Ru; , M=Os) and Cp*Ir(E2C2B10H10) (, E=S; , E=Se) with ethynylferrocene lead
      selectively to the 18e complexes (p-cymene)Ru(S2C2B10H9)(H2CCFc) (Fc=ferrocenyl)
      (), (p-cymene)Os(S2C2B10H9)(H2CCFc) (), Cp*Ir(S2C2B10H9)(H2CCFc) () and
      Cp*Ir(Se2C2B10H9)(H2CCFc) (), in which the alkyne is regio- and stereoselectively
      inserted into one of the M-E bonds that may further lead to metal-induced B-H
      activation, hydrogen atom transfer from the carborane via the metal center to the
      inserted alkyne, and the generation of a M-B bond. In all complexes the S-eta2
      (Fc)C-C and C-B(M) moieties occupy a cisoid position. The four new complexes are
      characterized by IR, MS, NMR spectroscopy and microanalysis, and the X-ray
      structural analysis of is performed. was observed to promote the uptake of
      anticancer drug daunorubicin in drug-resistant leukemia K562 cells.

PMID- 19089010
TI  - Theoretical study of N-dealkylation of N-cyclopropyl-N-methylaniline catalyzed by
      cytochrome P450: insight into the origin of the regioselectivity.
AB  - The mechanism of N-dealkylation of N-cyclopropyl-N-methylaniline () catalyzed by
      cytochrome P450 (P450) was investigated using density functional theory. This
      reaction involves two steps. The first one is a Calpha-H hydroxylation on the N
      substituent to form a carbinolaniline complex, and the second is a decomposition
      of the carbinolaniline to yield cyclopropanone (or formaldehyde) and N
      methylaniline (or N-cyclopropylaniline). Our calculations demonstrate that the
      first step proceeds in a spin-selective mechanism (SSM), mostly on the low-spin
      (LS) doublet state. The rate-limiting Calpha-H activation is an isotope-sensitive
      hydrogen atom transfer (HAT) step. The environmental effect switches the
      regioselectivity of this reaction from a competition between N-decyclopropylation
      and N-demethylation to a clear preference for N-demethylation. This preference is
      consistent with former experimental studies. However, it is not in accord with
      the normal DeltaE-BDE correlation since the BDE of Calpha-H on the methyl group
      is higher than that on the cyclopropyl group. Insight into the origin of the
      preference for N-demethylation reveals that tertiary amine is different from
      normal hydrocarbons, possessing a unique piPh-piC-N conjugated system. The
      electron delocalization effect of the piPh-piC-N conjugated system in makes the
      transition state pose a polar character, and the bulk polarity and hydrogen
      bonding capability of the protein pocket can exert a remarkable effect on the
      regioselectivity of N-dealkylation of . Decomposition of carbinolaniline is a
      water-assisted proton-transfer process in the nonenzymatic environment. The ring
      intact cyclopropanone formed in the reaction sheds some light on the inability of
      to inactivate P450 during its N-decyclopropylation.

PMID- 19089011
TI  - Lanthanide-doped luminescent ionogels.
AB  - Ionogels are solid oxide host networks confining at a meso-scale ionic liquids,
      and retaining their liquid nature. Ionogels were obtained by dissolving
      lanthanide(III) complexes in the ionic liquid 1-hexyl-3-methylimidazolium
      bis(trifluoromethylsulfonyl)imide, [C6mim][Tf2N], followed by confinement of the
      lanthanide-doped ionic liquid mixtures in the pores of a nano-porous silica
      network. [C6mim][Ln(tta)4], where tta is 2-thenoyltrifluoroacetonate and Ln=Nd,
      Sm, Eu, Ho, Er, Yb, and [choline]3[Tb(dpa)3], where dpa=pyridine-2,6
      dicarboxylate (dipicolinate), were chosen as the lanthanide complexes. The
      ionogels are luminescent, ion-conductive inorganic-organic hybrid materials.
      Depending on the lanthanide(III) ion, emission in the visible or the near
      infrared regions of the electromagnetic spectrum was observed. The work presented
      herein highlights that the confinement did not disturb the first coordination
      sphere of the lanthanide ions and also showed the excellent luminescence
      performance of the lanthanide tetrakis beta-diketonate complexes. The crystal
      structures of the complexes [C6mim][Yb(tta)4] and [choline]3[Tb(dpa)3] are
      reported.

PMID- 19089012
TI  - A MnII4 cubane and a novel MnII10MnIII4 cluster from the use of di-2-pyridyl
      ketone in manganese acetate chemistry.
AB  - The employment of di-2-pyridyl ketone, (py)2CO, in manganese(II) acetate
      chemistry is reported. The syntheses, crystal structures and magnetochemical
      characterisation are described for [MnII4(O2CMe)4{(py)2C(OH)O}4] () and
      [MnII10MnIII4O4(O2CMe)20{(py)2C(OH)O}4] (), where (py)2C(OH)O- is the monoanion
      of the gem-diol form of the ligand. The reaction of Mn(O2CMe)(2).4H2O with one
      equivalent of (py)2CO in Me2CO gives . Complex was obtained from the 1:1
      reaction, in EtOH, between Mn(O2CMe)(2).4H2O and (py)2CO in the presence of NEt3.
      The tetranuclear molecule has a cubane topology with the MnII and the
      deprotonated oxygen atoms from the eta1:eta3:eta1:micro3 ligands occupying
      alternate vertices of the cube. The core of consists of two mixed valence cubane
      {MnII2MnIII2(micro3-O)2(micro3-OR'')2}4+ subunits that are linked through an
      unusual {MnII6(eta1:eta2:micro-O2CMe)6(eta2:eta2:micro3-O2CMe)2}4+ moiety via
      twelve eta1:eta1:micro MeCO2- groups. Some suggestions have been made concerning
      the possible assembly of from . The magnetic properties of in the 300-5 K range
      have been modelled with two J values, which reveal weak antiferromagnetic
      interactions within the molecule. Complex has a low spin ground state. This work
      demonstrates the flexibility, versatility and synthetic potential of combining
      (py)2CO with carboxylate ligands.

PMID- 19089013
TI  - Two-electron oxidation of N,N,N',N'-tetramethylphenylenediamine with a
      chromium(v) salen complex.
AB  - The oxidation of tetramethylphenylenediamine (TMPD) with (salen)CrVO+ generates
      initially the 2-electron product TMPD2+, followed by the reaction with excess
      TMPD to yield the radical cation, TMPD+. The kinetics of both TMPD/(salen)CrVO+
      and TMPD/TMPD2+ reactions are acid-dependent, with TMPD being the most reactive
      form, and the doubly protonated TMPDH2(2+) exhibiting no discernible reactivity
      toward either (salen)CrVO+ or TMPD2+. The specific rate constants for the
      individual reactions are: TMPD/(salen)CrVO+, k=(6.28+/-0.50)x10(9) M(-1) s(-1),
      TMPDH+/(salen)CrVO+, (3.89+/-0.31)x10(5), TMPD/TMPD2+, (7.61+/-0.42)x10(8), and
      TMPDH+/TMPD2+, (3.46+/-0.22)x10(4).

PMID- 19089014
TI  - Synthesis and structure of electron rich ruthenium polyhydride complexes and
      clusters containing AlCp* and GaCp*.
AB  - The reactions of the ruthenium hydride complexes [{Ru(COD)(H)(NH2NMe2)3}{BArF}]
      (BArF=B{C6H3(CF3)2}4), [{Cp*Ru}2(micro-H)4] and [{Cp*Ru}3(micro-H)3(micro3-H)2]
      with GaCp* and AlCp* are investigated. The reaction of
      [{Ru(COD)(H)(NH2NMe2)3}{BArF}] with GaCp* leads to substitution of the hydrazine
      ligands by GaCp* and the formation of [{Ru(COD)(H)(GaCp*)3}{BArF}] (), while the
      reactions of [{Cp*Ru}2(micro-H)4] and [{Cp*Ru}3(micro-H)3(micro3-H)2] with ECp*
      (E=Al, Ga) results in the formation of the polyhydride clusters [{Cp*Ru(micro
      H)(H)(micro-ECp*)}2] (, E=Ga; , E=Al) and [{Cp*Ru}3(micro-H)5(micro3-ECp*)] (,
      E=Al; , E=Ga). All Ru complexes react upon coordination of the group 13 ligand
      without loss of H2 or reductive elimination of Cp*H and without insertion into
      the Ru-H bonds; some of the products, however, showing Ru-H-E bridging motifs.
      All compounds were characterized by NMR spectroscopy, elemental analysis and
      single crystal X-ray diffraction studies.

PMID- 19089015
TI  - Monitoring the carburization of molybdenum bimetallic nitrides and oxynitrides
      with CH4/H2/Ar mixtures: identification of a new carbonitride.
AB  - A new carbonitride Ni2Mo3(CxNy) has been synthesized by temperature-programmed
      carburization of the Ni2Mo3N precursor with a CH4/H2/Ar gas mixture at 923 K.
      This compound has been characterized by X-ray diffraction, elemental analysis,
      Auger electron spectroscopy, laser Raman spectroscopy, thermogravimetric analysis
      and field-emission scanning electron microscopy. Ni2Mo3(CxNy) crystallizes in the
      cubic space group P4(1)32, with a lattice parameter of a=6.64575(3) A,
      corresponding to the unusual filled beta-Mn structure. Its formation occurs by
      partial substitution of N by C via a topotactic and pseudomorphic reaction and
      its stability in air is higher that of Ni2Mo3N. A two-phase mixture with a cubic
      structure has always been obtained by the same synthetic method applied to the
      V2Mo(OxNy) precursor. One of these would be of carbidic nature formed at 1153 K
      following a reaction similar to that proposed for Ni2Mo3(CxNy).

PMID- 19089016
TI  - Dinuclear gold(I) and gold(III) complexes of bridging functionalized bis(N
      heterocyclic carbene) ligands: synthesis, structural, spectroscopic and
      electrochemical characterizations.
AB  - We report the synthesis of Au(I) and Au(III) complexes, involving alcohol
      functionalized bis(N-heterocyclic carbene) ligands. Two short reaction pathways
      lead to the diimidazolium precursors, namely 1,1'-(2,6-pyridinediyl)bis[3-(2
      hydroxyethyl)-1H-imidazol-3-ium]diiodide (), 3,3'(methanediyl)bis[1-(2-hydroxy-2
      methylpropyl)-1H-imidazol-3-ium]dibromide () and 3,3'-(1,3-propanediyl)bis[1-(2
      hydroxy-2-methylpropyl)-1H-imidazol-3-ium]bis(4-methylbenzenesulfonate) (), in
      which the two azolium rings are bridged by a rigid pyridine unit or an aliphatic
      chain (C1 or C3). The Au(I) complexes [AuI(Lpy)]2(2+)[PF6-]2 () and
      [AuI(LC1)]2(2+)[PF6-]2 () were obtained by direct metallation of the salts and ,
      respectively, in the presence of sodium acetate with Au(SMe(2))Cl, followed by an
      anionic metathesis in the presence of KPF6. The trimethylene compound
      [AuI(LC3)]2(2+)[PF6-]2 () was prepared by transmetallation between the related
      precursor [AgI(LC3)]2(2+)[PF6-]2 () and Au(SMe2)Cl. The Au(III) complexes,
      [AuIII(Lpy)Br2]2(2+)[PF6-]2 (), [AuIII(LC1)Br2]2(2+)[PF6-]2 () and
      [AuIII(LC3)Br2]2(2+)[PF6-]2 () were generated by oxidation of the corresponding
      Au(I) species with an excess of elemental bromine. Complexes , [AuI(LC1)]2(2+)[Br
      ]2 () and have been characterized by single-crystal X-ray diffraction analyses.
      The electrochemical and luminescence properties of the Au(I) and Au(III)
      compounds have been studied.

PMID- 19089017
TI  - Synthesis and structures of halides and pseudohalides of bis[2,6
      bis(dimethylamino)phenyl]tin(IV).
AB  - Oxidative addition reactions of Sn{C6H3(NMe2)(2)-2,6}2 [ identical with
      Sn(ArN2)2] () with XeF2, HgCl2 or TeCl4, dabco.2Br2, I2, or SiMe3N3 afforded
      [Sn(ArN2)2F2] (), [Sn(ArN2)2Cl2] (), [Sn(ArN2)2Br2] (), [Sn(ArN2)2I2] (), or
      [Sn(ArN2)2{N(SiMe3)2}N3] (), respectively. Compound was also obtained from and
      aqueous KF. Treatment of , under phase transfer conditions using [NBnEt3]Cl in
      H2O, with NaN3, KOCN, or KSCN yielded [Sn(ArN2)2(N3)2] (), [Sn(ArN2)2(NCO)2] (),
      or [Sn(ArN2)2(NCS)2] (), respectively. Alternative pathways to are suggested.
      Excellent (, and ) and satisfactory () yields were recorded; each compound was
      characterised by C, H, N microanalysis, mass spectra and multinuclear NMR
      solution spectra at ambient temperature, which invariably showed equivalent
      NMe2(1)H and 13C signals for the two NMe2 groups. The X-ray structures of
      crystalline [Sn(ArN2)Cl] (), , , , and showed that only one of the 2- and 6-Me2N
      substituents of an (ArN2) group was in a close SnN contact. Reaction of with
      Li[AlMe4] or LiMe gave [Sn(ArN2)(micro-Me)2AlMe2] () or c-(SnMe2)6, respectively.

PMID- 19089018
TI  - Distortional isomerism with copper(I) complexes of 3,7-diazabicyclo[3.3.1]nonane
      derivatives.
AB  - Two structural forms of the tetradentate bispidine ligand (3,7
      diazabicyclo[3.3.1]nonane, pyridine-substituted at C2 and C4), coordinated to
      CuI, are known: a pentacoordinate square pyramidal structure with an acetonitrile
      completing the coordination sphere, and a tetracoordinate distorted tetrahedral
      structure, where one of the pyridine groups is dissociated. Similar structures
      are observed in crystals of the CuI complexes of another tetradentate and two
      pentadentate bispidine ligands. The structural dynamics in the CuI coordination
      sphere of the four ligands are probed by 1H-NMR spectroscopy, supported by
      approximate density functional theory (DFT) calculations. DFT and NMR
      spectroscopy indicate that there is an additional isomeric form, and experimental
      as well as computational data lead to the conclusion that the potential energy
      surfaces are very flat with various shallow minima.

PMID- 19089019
TI  - Synthesis and coordination chemistry of TpC*MI complexes where M=Mg, Ca, Sr, Ba
      and Zn and TpC*=tris[3-(2-methoxy-1,1-dimethyl)pyrazolyl]hydroborate.
AB  - Reactions involving MI2 where M=Mg, Ca, Sr, Ba or Zn and M'TpC* where M'=Na or Tl
      and TpC*=tris[3-methoxy-1,1-dimethyl)pyrazolyl]hydroborate in tetrahydrofuran are
      described leading to the isolation and characterization of the complexes TpC*MgI,
      , TpC*CaI, , TpC*SrI, , TpC*SrI(THF), , TpC*BaI, , TpC*BaI(pz*H), , where pz*H=3
      (2-methoxyl-1,1-dimethyl)pyrazole, TpC*BaI.1/2toluene, and TpC*ZnI, . The
      compounds , , , , and have been characterized by single-crystal X-ray
      crystallography. Compounds and are isostructural and are salt-like containing
      kappa6-TpM+ cations and I- anions. In all other structures, the iodide is bound
      to the metal and TpC* is kappa6 bonded to the group 2 M(2+) ions. Reactions
      involving TpC*CaI, , and sodium or lithium alkoxides or amides failed to yield
      the amide or alkoxide calcium TpC* derivative, though related reactions involving
      TpC*ZnI, , and KOSiMe3 proceeded quantitatively to yield kappa3TpC*ZnOSiMe3, ,
      which was also structurally characterized and shown to have the kappa3-TpC* bound
      ligand.

PMID- 19089020
TI  - Synthesis of new copper(I) complexes with tris(2-pyridyl) ligands. Applications
      to carbene and nitrene transfer reactions.
AB  - New copper(I) complexes with tris(2-pyridyl)methane (TPC), tris(2
      pyridyl)methoxymethane (TPM) and tris(2-pyridyl)amine (TPN) ligands have been
      synthesized and characterized, including structural determinations by X-ray
      diffraction of some examples. Their activity as catalysts in carbene and nitrene
      transfer reactions was studied.

PMID- 19089021
TI  - Effectiveness of NaOCl alone or in combination with EDTA on the diffusion of
      hydroxyl ions released by calcium hydroxide paste.
AB  - AIM: To evaluate the effect of different irrigant solutions employed during
      removal and replacement of calcium hydroxide paste on the diffusion of hydroxyl
      ions through root canal dentine in vitro. METHODOLOGY: Thirty-five maxillary and
      mandibular human canines with straight and fully developed roots were used. After
      mechanical preparation up to 1mm short of tooth length, 30 canals were filled
      with calcium hydroxide paste and 5 canals were left empty; all teeth had their
      coronal accesses properly sealed. Teeth were placed in plastic containers with
      distilled water, and pH was read after 30 days when the paste from 20 teeth was
      renewed. After removal of the paste by endodontic instrumentation and irrigation
      with distilled water, canals were replenished with newly mixed paste in Group 1
      and 2. In these groups, final irrigation was conducted with 5 mL of EDTA followed
      by 5 mL of NaOCl in specimens in Group 1, and 5 mL of NaOCl only in specimens in
      Group 2. In 10 teeth the paste was not replenished at 30 days (Group 3). All
      specimens were returned to the containers with fresh distilled water, and the pH
      was recorded after another 30 days. The differences between the first (30d) and
      second (60d) pH readings were calculated and submitted to analysis of variance
      and individual comparisons using the Scheffee's test. RESULTS: Results of mean
      analysis on differences of pH readings showed that greater diffusion had occurred
      on specimens in Group 3. Individual comparisons using Scheffee's test showed
      statistical significance between Groups 2 and 3, and equivalence between all
      other groups. CONCLUSION: It was concluded that the use of EDTA did not enhance
      diffusion of hydroxyl ions through root canal dentine.

PMID- 19089022
TI  - Comparison of the cleaning efficacy of the FKG race system and hand instrument in
      molar root canal.
AB  - INTRODUCTION AND OBJECTIVE: The aim of this study was to evaluate the ability of
      root canal cleaning of the RaCe rotary instrumentation system (FKG Dentaire - La
      Cheaux-de Fonds - Switzerland), compared to manual filing with Stainless Steel K
      files (Maillefer Instruments - Ballaigues - Switzerland). MATERIAL AND METHOD:
      Twenty extracted human teeth (maxillary molars) were selected and their pulp
      tissue was removed after coronal access. The root canals were filled with a dye
      (India ink) and allowed to dry for 48 hours, followed by establishment of the
      working length of the mesiobuccal root; then, half of the specimens were
      instrumented by the modified Oregon technique and the other half were
      instrumented by crown-down sequence of the RaCe system. After preparation, the
      teeth were longitudinally sectioned and evaluated according to the amount of
      remaining dye. RESULTS: Data obtained were registered as numerical scores, and
      the arithmetic means were compared between groups using the Mann Whitney test.
      Both techniques were unable to completely clean the interior of the root canals,
      with a better performance of the manual technique only at the middle third.
      CONCLUSION: It could be concluded that the RaCe system was able to provide
      satisfactory cleaning, similar to that obtained by the manual instrumentation
      technique.

PMID- 19089023
TI  - Influence of light curing source on microhardness of composite resins of
      different shades.
AB  - INTRODUCTION: The evolution of light curing units can be noticed by the different
      systems recently introduced. The technology of LED units promises longer
      lifetime, without heating and with production of specific light for activation of
      camphorquinone. However, further studies are still required to check the real
      curing effectiveness of these units. PURPOSE: This study evaluated the
      microhardness of 4 shades (B-0.5, B-1, B-2 and B-3) of composite resin Filtek Z
      250 (3M ESPE) after light curing with 4 light sources, being one halogen
      (Ultralux - Dabi Atlante) and three LED (Ultraled - Dabi Atlante, Ultrablue - DMC
      and Elipar Freelight - 3M ESPE). METHODS: 192 specimens were distributed into 16
      groups, and materials were inserted in a single increment in cylindrical
      templates measuring 4mm x 4mm and light cured as recommended by the manufacturer.
      Then, they were submitted to microhardness test on the top and bottom aspects of
      the cylinders. RESULTS: The hardness values achieved were submitted to analysis
      of variance and to Tukey test at 5% confidence level. It was observed that
      microhardness of specimens varied according to the shade of the material and
      light sources employed. The LED appliance emitting greater light intensity
      provided the highest hardness values with shade B-0.5, allowing the best curing.
      On the other hand, appliances with low light intensity were the least effective.
      It was also observed that the bottom of specimens was more sensitive to changes
      in shade. CONCLUSION: Light intensity of LED light curing units is fundamental
      for their good functioning, especially when applied in resins with darker shades.

PMID- 19089024
TI  - Digital radiographic evaluation of optical density of porcelains used for
      fabrication of inlay/onlay prosthesis.
AB  - The purpose of this article was to compare the mean value of optical density of
      four porcelains commonly used for fabrication of inlay/onlay prostheses using
      direct digital radiograph. The sample consisted of 20 2-mm thick porcelain
      specimens (measured by digital pachymeter): Empress (Ivoclair), Simbios
      (Degussa), Vita Omega 900 and Vitadur Alpha (Vita Zahnfabrik). The values of
      optical density of the specimens were expressed in millimeters aluminum
      equivalent (mm eq Al). The samples were X-rayed using two charge coupled devices
      (CCD) - RVG (Trophy) - Visualix (Gendex) and a phosphor plate system - Digora
      (Soredex). The optical density reading was performed with Image Tool 1.28 in a
      total of 110 measurements. Statistical analysis showed that there were
      statistically significant differences in all materials studied (p < 0.05)
      regardless of the radiographic system used. The highest optical density value was
      found for Omega 900 (1.8988 mmeqAl - Visualix - Gendex) and the lowest for
      Vitadur Alpha (0.8647 - Visualix - Gendex). Thus, the material presenting the
      highest degree of optical density was Omega 900, Empress and Simbios presented
      intermediate optical density values, Vitadur Alpha presented the lowest value,
      and the optical density of porcelains was not influenced by the digital
      radiography systems.

PMID- 19089025
TI  - Massage therapy in the management of myogenic TMD: a pilot study.
AB  - INTRODUCTION: The Temporomandibular disorder (TMD) is greatly prevalent in the
      population and can be associated with bruxism. This disorder produces several
      signs and symptoms. Among them, pain is one of the most important because it
      reduces life quality and productivity of people who have such disorder. The aim
      of this research was to study if massage causes pain relief and/or
      electromyographic (EMG) changes. MATERIALS AND METHODS: The subjects were chosen
      by a questionnaire and divided into 2 different groups. Their ages varied from 19
      to 22 years. The experimental group consisted of 6 TMD patients, who were
      submitted to the massage treatment and 4 EMG-sessions (the 1st EMG-session
      occurred before the treatment and the others in the 1st, 15th and 30th days after
      the treatment). The control group consisted of 6 TMD patients, who were submitted
      to the same 4 EMG-sessions. While EMG activity was recorded, subjects were asked
      to keep mandibular rest position (MRP) and to perform maximal voluntary clenching
      (MVC). The treatment consisted of 15 massage-sessions on face and neck and in
      application of Visual Analogue Scale (VAS) for measuring pain level. The massage
      sessions had 30 minutes of duration and were performed daily. The EMG data were
      processed to obtain the Root Mean Square (RMS), which were normalized by MVC.
      RESULTS: It was demonstrated that (1) RMS-MRP of the right masseter in
      experimental group at the 1st EMG-session was higher than at the 2nd EMG-session
      and (2) statistically significant reduction was found for VAS values after
      massage session. CONCLUSION: Unfortunately the sample is insufficient to draw any
      conclusions, therefore, more studies regarding the use of massage in the
      management of myogenic TMD are necessary.

PMID- 19089026
TI  - Longitudinal photographic observation of the occurrence of bubbles in pit and
      fissure sealants.
AB  - The purpose of this study was to employ photographic evaluation to observe the
      presence or absence of bubbles in pit and fissure sealants Concise and Prisma
      Shield, at 7 days, 18 months, 36 months and 11 years after accomplishment of
      treatment. METHODS: A hematoxylin-based staining solution was applied to the
      occlusal surface at the study periods, which allowed assessment of the sealing
      material on the surface. All occlusal surfaces were photographed and the
      photographs corresponding to each period were subjected to photographic
      evaluation. RESULTS: There was statistically significant difference only at 18
      months, with a significantly higher number of specimens with bubbles for the
      Prisma Shield sealant compared to the Concise, whereas the groups were similar at
      all other study periods. On the other hand, separate analysis of subsequent
      periods of the sealants did not reveal any significant difference. CONCLUSIONS:
      According to the results of the present longitudinal investigation, it may be
      concluded that the sealing materials showed that bubbles came into and went out
      with time. However, this fact did not interfere with its clinical purpose,
      provided the remaining material covers the expected region of pits and fissures.

PMID- 19089027
TI  - Influence of iodoform on antimicrobial potential of calcium hydroxide.
AB  - The purpose of this research was to verify the influence of Iodoform on
      antimicrobial potential of calcium hydroxide. S. aureus, E. faecalis, P.
      aeruginosa, B. subtilis, C. albicans were the biological indicators. The
      substances tested were: calcium hydroxide + saline; calcium hydroxide + Iodoform
      + saline; Iodoform + saline. For the agar diffusion test, 18 Petri plates with 20
      ml of BHI agar were inoculated with the microbial suspensions. Fifty-four
      cavities were made and filled with the substances tested. The diameters of
      microbial inhibition were then measured. In direct exposure test, 162 #50 sterile
      absorbent paper points were immersed in the experimental suspensions for 5 min,
      and covered with the pastes. At intervals of 24, 48 and 72 hours, the paper
      points were immersed in 10 ml of Letheen Broth, followed by incubation at 37
      degrees C for 48h. Microbial growth was evaluated by turbidity of the culture
      medium. A 0.1 ml inoculum obtained from the Letheen Broth was transferred to 7 ml
      of BHI, and incubated at 37 degrees C for 48h. Bacterial growth was again
      evaluated by turbidity of the culture medium. The calcium hydroxide associated
      with the saline or the iodoform plus saline showed antimicrobial effectiveness in
      both experimental methods. The iodoform paste presented antimicrobial
      ineffectiveness for the agar diffusion test on all biological microorganisms and
      for the direct exposure test on B. subtilis and on the mixture.

PMID- 19089028
TI  - Fluoride content of UHT milks commercially available in Bauru, Brazil.
AB  - OBJECTIVES: The aims of the present study were to evaluate the fluoride (F)
      concentrations in whole, defatted and chocolate milks commercially available in
      Brazil and to estimate the daily F intake from these sources. MATERIAL AND
      METHODS: F concentrations were determined for 23 brands of milks, after HMDS
      facilitated diffusion, using a F ion-specific electrode. Possible F ingestion per
      kg body weight was estimated, based on suggested volumes of formula consumption,
      for infants aging 1 to 12 months. RESULTS: F concentrations ranged from 0.02 to
      1.6 microg/mL F for all brands analyzed. Whole and defatted milks had the lowest
      F concentrations, ranging from 0.02 to 0.07 microg/mL. With respect to chocolate
      milks, three brands had F concentrations above 0.5 microg/mL. Some brands of
      chocolate milks exceeded the dose regarded as the threshold level for the
      development of dental fluorosis, without taking into account other sources of
      fluoride intake. CONCLUSION: The high fluoride concentrations found in some
      brands of chocolate milks in the present study indicate that many products may be
      important contributors to the total fluoride intake, reinforcing the need of
      assaying fluoride content of foods and beverages consumed by small children.

PMID- 19089029
TI  - In vivo evaluation of the sealing ability of two endodontic sealers in root
      canals exposed to the oral environment for 45 and 90 days.
AB  - This in vivo study evaluated the sealing ability of a resin-based sealer (AH
      Plus) and a zinc oxide-eugenol sealer (Endofill) in dogs' teeth, exposed to the
      oral environment for 45 and 90 days. Forty eight lower incisors from 8 dogs were
      endodonticaly treated. A stratified randomization determined the sealer use in
      each root canal. All canals were filled using the lateral condensation technique.
      The excess filling material at the cervical portion of the root canal was
      sectioned, leaving a 10-mm obturation length inside the canal. Teeth were
      provisionally sealed with glass ionomer cement for 24 h and the canals were
      exposed to the oral environment for either 45 or 90 days. Therefore, the
      experimental groups were as follows: A45- AH Plus for 45 days; A90- AH Plus for
      90 days; E45- Endofill for 45 days; and E90- Endofill for 90 days (n=12). After
      the experimental period, the dogs were killed and the lower jaw was removed. The
      incisors were extracted and the roots were covered with two coats of nail
      varnish. The teeth were immersed in India ink for 96 h and submitted to
      diaphanization. Dye leakage (in mm) was measured using stereomicroscopy (10x
      magnification). The results were statistically analyzed using two-way ANOVA and
      Tukey test for multiple comparisons (a = 0.05). Group E90 (2.03+/-0.94) showed
      significantly higher mean leakage value than all other groups (p<0.001). None of
      the sealers, in both study conditions, were able to prevent dye leakage.

PMID- 19089030
TI  - In vitro evaluation of apical microleakage using different root-end filling
      materials.
AB  - The objective of this study was to evaluate the apical leakage of retrograde
      cavities filled with Portland Cement (Concrebras S/A-MG-Brazil), ProRoot MTA
      (Dentsply International, Johnson City, TN, USA) and Sealapex (Kerr Corporation,
      Orange, California, USA) with addition of zinc oxide (Odahcam Herpo Produtos
      Dentarios Ltda, Rio de Janeiro, RJ, Brazil). Forty-two extracted single-rooted
      human teeth were decoronated and used for this study. The root canals were
      instrumented at 1.0mm short of the apical foramen using the step-back technique
      to an apical ISO size 60. The roots were obturated with gutta-percha points and
      sealer Sealapex (Kerr Corporation-USA) and then 3mm of each root apex was
      sectioned at a 90 degrees angle. Ultrasonic retrograde preparation was performed
      with a diamond tip to 3mm depth and the roots were randomly divided into 3 groups
      according to the filling material: G1-Portland, G2-ProRoot MTA, G3- Sealapex zinc
      oxide-added cement. The root surfaces were covered with nail varnish up to 2mm
      from the apical foramen, immersed in simulated tissue fluid for 30 days, and then
      immersed in 0.2% Rhodamine B solution for 24 hours for evaluation of marginal
      leakage. The results showed mean leakage of 0.75, 0.35 and 0.35 for groups 1, 2
      and 3, respectively; however, Kruskal-Wallis test revealed that there was no
      statistically significant difference among the results (p>0.05).

PMID- 19089031
TI  - Dental caries in children that participated in a dental program providing mother
      and child care.
AB  - The main goal of this study was to evaluate the prevalence of caries in children
      that participate in a dental program attending mothers and children in Teresina,
      Piaui, Brazil. A selection was made of 343 children of both genders, from 3 to 6
      years of age. The mothers answered questionnaires and children were examined at
      the Infant Dental Clinic of the Federal University of Piaui. The epidemiological
      index dmft was applied and active white spot lesions were included. The SPSS for
      Windows program, version 11.1 was used and non-parametric tests carried out
      (Friedman and Kruskal-Wallis). An alpha error of 5% (0.05) was considered for the
      null hypothesis of false rejection, with a confidence interval of 95%. The
      results showed that 57.5% (197) of the children were breast-fed for a period
      longer than 12 months. The mean dmft index and percentages of caries-free
      children at the age of 3 was 1.86 (58.82%); at 4 years of age 1.94 (57.60%); at 5
      years of age 1.98 (56.86%) and at 6 years of age 2.42 (42.55%). The decay
      component (d) was prevalent at all ages. When active white spot lesions were
      added to the dmft index, there was an increase of 7.2% for children who had
      caries activity and/or previous caries experience and 2.61% for those with dmft
      equal to zero. The daily consumption of fermentable carbohydrates and free demand
      breast-feeding were factors increasing caries activity. Dental follow-up after
      the program and the number of daily brushings were shown to be factors providing
      protection against caries. Based on the results, the authors were able to
      conclude that the program caused a positive impact on caries disease control, as
      the number of dental appointments kept influenced the dmft index values in a
      statistically significant manner.

PMID- 19089032
TI  - Evaluation of microcurrent electrical nerve stimulation (MENS) effectiveness on
      muscle pain in temporomandibular disorders patients.
AB  - The effect of Microcurrent Electrical Nerve Stimulation (MENS) was evaluated and
      compared with occlusal splint therapy in temporomandibular disorders (TMD)
      patients with muscle pain. Twenty TMD patients were divided into four groups. One
      received occlusal splint therapy and MENS (I); other received splints and placebo
      MENS (II); the third, only MENS (III) and the last group, placebo MENS (IV).
      Sensitivity derived from muscle palpation was evaluated using a visual analogue
      scale. Results were submitted to analysis of variance (p<0.05). There was
      reduction of pain level in all groups: group I (occlusal splint and MENS) had a
      47.7% reduction rate; group II (occlusal splint and placebo MENS), 66.7%; group
      III (MENS), 49.7% and group IV (placebo MENS), 16.5%. In spite of that, there was
      no statistical difference (analysis of variance / p<0.05) between MENS and
      occlusal splint therapy regarding muscle pain reduction in TMD patients after
      four weeks.

PMID- 19089033
TI  - Biocompatibility of acellular dermal matrix graft evaluated in culture of murine
      macrophages.
AB  - The acellular dermal matrix allograft has been used as an alternative to
      autogenous palatal mucosal graft. The aim of this study was the evaluation of the
      biocompatibility of an acellular dermal matrix (AlloDerm) in culture of
      macrophages. For hydrogen peroxidase determination we used the method of Pick &
      Kesari, and the Griess method for nitric oxide determination. Statistical
      analysis showed no significant difference (p <or= 0,05) in the release of nitric
      oxide and hydrogen peroxide by the macrophages exposed to acellular dermal matrix
      and the negative control. The results suggest that acellular dermal matrix did
      not activate the cell inflammatory response.

PMID- 19089034
TI  - Depth of cure of dental composites submitted to different light-curing modes.
AB  - OBJECTIVE: This study evaluated the depth of cure of five dental composites
      submitted to different light-curing modes. MATERIAL AND METHODS: Canal-shaped
      cavities with 5mm of length were prepared on the buccal surfaces of extracted
      third molars, and restored using P-60, A-110, Admira, Z-250 and Supreme resin
      composites. Materials were light-cured from the top, according to three modes
      (Group 1- Conventional (C): 500 mW/cm(2) / 40 s; Group 2 - Soft-Start (SS): 250
      mW/cm(2)/ 20 s + 500 mW/cm(2)/ 20 s + 500 mW/cm(2)/ 10 s and Group 3 - LED: 250
      mW/cm(2)/ 40 s). After that, cavity longitudinal surfaces were polished and
      marked with a millimeter scale of 4mm of length. Depth of cure was evaluated by
      means of Knoop hardness number (KHN), so that five indentations were performed at
      each millimeter. Original data were submitted to three-way ANOVA and Fisher's LSD
      test (alpha = 0.01). RESULTS: All materials presented a significant reduction on
      KHN from first to third millimeter. Regarding depth of cure, the results obtained
      for Conventional and Soft-Start modes were similar, but statistically superiors
      to those found for group 3 (LED). CONCLUSION: This performance may be related to
      the differences among energy densities obtained with different light-curing
      modes.

PMID- 19089035
TI  - The influence of screw type, alloy and cylinder position on the marginal fit of
      implant frameworks before and after laser welding.
AB  - Misfit at the abutment-prosthetic cylinder interface can cause loss of preload,
      leading to loosening or fracture of gold and titanium screws. OBJECTIVES: To
      evaluate the influence of screw type, alloy, and cylinder position on marginal
      fit of implant frameworks before and after laser welding. METHODS: After
      Estheticone-like abutments were screwed to the implants, thirty plastic
      prosthetic cylinders were mounted and waxed-up to fifteen cylindrical bars. Each
      specimen had three interconnected prosthetic components. Five specimens were one
      piece cast in titanium and five in cobalt-chromium alloy. On each specimen, tests
      were conducted with hexagonal titanium and slotted gold screws separately,
      performing a total of thirty tested screws. Measurements at the interfaces were
      performed using an optical microscope with 5mm accuracy. After sectioning,
      specimens were laser welded and new measurements were obtained. Data were
      submitted to a four-way ANOVA and Tukey's multiple comparisons test (alpha=0.05).
      RESULTS: Slotted and hexagonal screws did not present significant differences
      regarding to the fit of cylinders cast in titanium, either in one-piece casting
      framework or after laser welding. When slotted and hexagonal screws were tested
      on the cobalt-chromium specimens, statistically significant differences were
      found for the one-piece casting condition, with the slotted screws presenting
      better fit (24.13 microm) than the hexagonal screws (27.93 microm). Besides, no
      statistically significant differences were found after laser welding.
      CONCLUSIONS: 1) The use of different metal alloys do exert influence on the
      marginal fit, 2) The slotted and hexagonal screws play the exclusive role of
      fixing the prosthesis, and did not improve the fit of cylinders, and 3) cylinder
      position did not affect marginal fit values.

PMID- 19089036
TI  - Effect of carbamide peroxide-based bleaching agents containing fluoride or
      calcium on tensile strength of human enamel.
AB  - OBJECTIVE: The aim of this study was to evaluate the effects of carbamide
      peroxide-based bleaching agents (CPG) containing fluoride (CF) or calcium (CCa)
      on the ultimate tensile strength of enamel (UTS). METHOD: A "cube-like" resin
      composite structure was built-up on the occlusal surface of twenty-two sound
      third molars to facilitate specimen preparation for the micro-tensile test. The
      restored teeth were serially sectioned in buccal-lingual direction in slices with
      approximate 0.7 mm thickness. Each slice was trimmed with a fine diamond bur to
      reduce the buccal, internal slope enamel of the cusps to a dumb-bell shape with a
      cross-sectional area at the "neck" of less than 0.5 mm(2). The samples were
      randomly divided into 12 groups (n=11). The control groups were not submitted to
      the bleaching regimen. Specimens were treated with 10% CPG gel or with 10% CPG
      formulations containing CF (0.2% and 0.5%) or CCa (0.05% and 0.2%). Bleached
      groups received the application of the 10% CPGs for 6 hours/day at 37 degrees C,
      during 14 consecutive days and were stored in artificial saliva (AS) or 100%
      relative humidity (RH) among each application. After bleaching, specimens were
      tested with the microtensile method at 0.5 mm/min. Data were analyzed by two-way
      ANOVA and Tukey test (5%). RESULTS: No significant difference was observed
      between groups stored in AS or RH. Specimens treated with CF or CCa presented
      similar UTS as unbleached control groups. CONCLUSION: Either 10% CPG formulations
      containing CF or CCa can preserve the UTS after bleaching regimen.

PMID- 19089037
TI  - Effect of fluoridated varnish and silver diamine fluoride solution on enamel
      demineralization: pH-cycling study.
AB  - OBJECTIVE: In the present investigation, the anticariogenic effect of fluoride
      released by two products commonly applied in infants was evaluated. METHODS:
      Bovine sound enamel blocks were randomly allocated to each one of the treatment
      groups: control (C), varnish (V) and diamine silver fluoride solution (D). The
      blocks were submitted to pH cycles in an oven at 37 degrees C. Next, surface and
      cross-sectional microhardness were assessed to calculate the percentage loss of
      surface microhardness (%SML) and the mineral loss (deltaZ). The fluoride present
      in enamel was also determined. RESULTS: F/Px10(-3) (ANOVA, p<0.05) in the 1st
      layer of enamel before pH-cycling were (C, V and D): 1.61; 21.59 and 3.98. The
      %SMH (Kruskal-Wallis, p<0.05) were: -64.0, -45.2 and -53.1. %deltaZ values
      (ANOVA, p<0.05) were: -18.7 feminine, -7.7 and -17.3 feminine. CONCLUSION: The
      data suggested that the fluoride released by varnish showed greater interaction
      with sound enamel and provided less mineral loss when compared with silver
      diamine solution.

PMID- 19089038
TI  - Delayed tooth replantation after root surface treatment with sodium hypochlorite
      and sodium fluoride: histomorphometric analysis in rats.
AB  - In cases of delayed tooth replantation, non-vital periodontal ligament remnants
      have been removed with sodium hypochlorite in an attempt to control root
      resorption. Nevertheless, reports of its irritating potential in contact with the
      alveolar connective tissue have been described. Therefore, this study evaluated
      the healing process on delayed replantation of rat teeth, after periodontal
      ligament removal by different treatment modalities. Twenty-four rats, assigned to
      3 groups (n=8), had their upper right incisor extracted and left on the workbench
      for desiccation during 60 min. Afterwards, the teeth in group I were immersed in
      saline for 2 min. In group II, root surfaces were scrubbed with gauze soaked in
      saline for 2 min; and in group III, scrubbing was done with gauze soaked in 1%
      sodium hypochlorite solution. Thereafter, root surfaces were etched with 37%
      phosphoric acid and immersed in 2% acidulate-phosphate sodium fluoride solution,
      at pH 5.5. Root canals were filled with a calcium hydroxide-based paste and the
      teeth were replanted. The animals were sacrificed 60 days postoperatively and the
      pieces containing the replanted teeth were processed and paraffin- embedded. Semi
      serial transversally sections were obtained from the middle third of the root and
      stained with hematoxylin and eosin for histomorphometric analysis. Data were
      analyzed statistically using Kruskal-Wallis and Dunn's tests. The results showed
      that root structure and cementum extension were more affected by resorption in
      group III (p<0.05). All groups were affected by root resorption but the treatment
      performed in group III was the least effective for its control. The treatment
      accomplished in groups I and II yielded similar results to each other.

PMID- 19089039
TI  - Fiber-reinforced fixed partial dentures: a preliminary retrospective clinical
      study.
AB  - The aim of this study was to evaluate the clinical performance (retention rate)
      of fiber-reinforced composite fixed partial dentures (FPDs). Polyethylene fiber
      (Ribbond) was used combined with restorative composite during FPDs fabrication.
      FPDs were placed in thirteen patients in a private clinic. Nineteen FPDs were
      evaluated. The prosthetic space was filled with only one pontic using extracted
      teeth (2 cases), acrylic resin teeth (11 cases), or with composite resin (6
      cases), combined with Polyethylene fiber. The clinical criterion used was based
      on retention rate of FPDs. If FPDs were in function in the mouth at the time of
      examination without previous repair they were classified as Complete Survival
      (CS) restorations. A classification of Survival with Rebonding (SR) was assigned
      in the event of an adhesive failure, but after rebonding the FPD still remained
      under evaluation. Treatment was classified as a Failure (F) if the FPD
      restoration was lost. The time of evaluation was 41.15 months (+/-15.13). The
      FPDs evaluated were retained (CS=94.75%), and no failure was found except for in
      one situation which required rebonding (SR=5.25%). According to the survival
      estimation method of Kaplan-Meyer the mean survival time was 42.3 months. At the
      time of evaluation investigated, polyethylene-reinforced FPDs showed a favorable
      retention rate in preliminary data.

PMID- 19089040
TI  - In vivo microbiological evaluation of the effect of biomechanical preparation of
      root canals using different irrigating solutions.
AB  - The aim of this study was to evaluate the antimicrobial effect of biomechanical
      preparation using different irrigating solutions. Seventy-eight root canals from
      premolars of four dogs were used. After experimental induction of periapical
      lesions, the root canals were prepared using the following solutions for
      irrigation: Group 1) 2.5% sodium hypochlorite (NaOCl); Group 2) 2% chlorhexidine
      (CHX); Group 3) saline solution and Group 4) control group with no biomechanical
      preparation. The microbiological evaluation of the root canals was performed by
      counting the colony forming units (CFUs) using different culture mediums. Two
      absorbent paper cones were used in each root canal in order to collect the
      microbiological samples before, and thirty days after the biomechanical
      preparation. The culture plates were incubated in aerobic, anaerobic and
      microaerophilic environment. Statistical evaluation was carried out using
      analysis of variance, Tukey and Student tests. The results demonstrated that
      there was reduction in the number of microorganisms in the NaOCl and CHX groups
      (p<0.05). There was greater effectiveness in the chlorhexidine group. The group
      that used saline solution and the control group presented an increased number of
      microorganisms. It can be concluded that the use of antimicrobial irrigating
      solutions during biomechanical preparation promotes the reduction of endodontic
      microbiota. However, a considerable number of microorganisms were still observed.

PMID- 19089041
TI  - Functional evaluation of oral rehabilitation with removable partial dentures
      after five years.
AB  - Most removable partial denture (RPD) wearers are satisfied with their prostheses,
      but the factors that influence satisfaction and acceptance are still not
      determined. OBJECTIVE: This study explored technical, biological, and
      satisfaction variables for the functioning of RPDs after five years, and compared
      the evaluation by the patient and by the clinician. MATERIAL AND METHODS: Fifty
      adults (39 females, 11 males) were re-examined after five years of RPD service.
      Data were collected through clinical examination and a structured questionnaire
      to record the conditions of supporting soft tissues, prosthesis acceptance and
      technical characteristics, mastication, esthetics, comfort, hygiene, and need for
      professional intervention. Data were analyzed by descriptive statistics and
      Spearman correlation. RESULTS: More than 50% of patients classified their RPDs as
      excellent regarding retention, mastication, esthetics, comfort, and hygiene. In
      the professional evaluation, retention and stability were considered excellent in
      more than 66% of cases, and hygiene of teeth and prostheses was considered good
      in 52% and 46%, respectively. The metallic framework and acrylic base were
      considered adapted in 92% of cases. Prosthesis acceptance was associated with
      retention, mastication, esthetics, hygiene, and comfort evaluated by the patient,
      and with retention, stability, and condition of the framework evaluated by the
      clinician. Retention and mastication/comfort evaluated by the patient had
      moderate positive correlation with retention and stability measured by the
      clinician. There was no association of hygiene evaluation by the patient and by
      the clinician. CONCLUSIONS: After five years, the oral rehabilitation with RPDs
      was satisfactory for most cases. There was correspondence between
      retention/retention and mastication-comfort/stability variables evaluated by the
      patient and by the clinician. Oral and prosthesis hygiene were not related.

PMID- 19089042
TI  - Effect of different prophylaxis methods on sound and demineralized enamel.
AB  - Considering the importance of professional plaque control for caries prevention,
      this study comprised an in vitro evaluation of wear by two prophylaxis methods
      (sodium bicarbonate jet - Profident and pumice and brush) on sound bovine enamel
      and with artificial carious lesions. Sixty enamel fragments were employed
      (4x4mm), which were divided into 4 groups: GI - 15 sound blocks treated with
      pumice and brush; GII - 15 sound blocks treated with Profident; GIII - 15
      demineralized blocks treated with pumice and brush, and GIV - 15 demineralized
      blocks treated with Profident. In the fragments of Groups III and IV, artificial
      carious lesions were simulated by immersion in 0.05M acetic acid solution 50%
      saturated with bovine enamel powder at 37 degrees C for 16h. The specimens were
      submitted to the prophylactic treatments for 10 seconds. Wear analysis was
      performed by profilometer and revealed the following results: 0.91microm - GI;
      0.42microm - GII; 1.6microm - GIII, and 0.94microm - GIV. The two-way ANOVA and
      Tukey's test (p<0.05) revealed significant difference between all groups.
      Scanning electron microscopy images were employed to illustrate the wear pattern,
      with observation of larger alteration on the demineralized enamel surface (GIII;
      GIV), round-shaped wear on GI and GIII and blasted aspect on GII and GIV. The
      study indicated that the demineralized enamel presented more wear than the sound
      enamel, and the brush led to larger wear when compared to Profident.

PMID- 19089043
TI  - Comparative in vitro study of root roughness after instrumentation with
      ultrasonic and diamond tip sonic scaler.
AB  - OBJECTIVE: The purpose of this study was to evaluate the root surface roughness
      after instrumentation with hand curette and diamond-coated sonic and universal
      ultrasonic tips. MATERIALS AND METHODS: Forty root surfaces of human teeth were
      randomly assigned to four treatment groups: control group (without
      instrumentation), curette instrumentation, ultrasonic instrumentation with
      universal tip and sonic instrumentation with diamond-coated tip. Each sample was
      instrumented with fifteen strokes. Before and after instrumentation, surface
      roughness was measured. In addition, the root surface topography was examined
      after treatment under the scanning electron microscope. RESULTS: Significant
      statistical differences (p <0.05) were observed when comparing the control group
      (0.48+/-0.07mm) to the treated groups (hand - 1.246+/-0.279mm, ultrasonic -
      1.468+/-0.177mm and sonic instrumentation - 1.576+/-0.20mm). The highest
      roughness was produced by diamond-coated sonic tip and by ultrasonic universal
      tip (p >0.05). CONCLUSION: The diamond-coated tip with sonic scaler
      instrumentation and ultrasonic instrumentation produce similar root surface
      roughness, higher than curette instrumentation.

PMID- 19089044
TI  - TENS and low-level laser therapy in the management of temporomandibular
      disorders.
AB  - Pain relief and reestablishment of normal jaw function are the main goals of
      conservative management of Temporomandibular Disorders (TMD). Transcutaneous
      electrical nerve stimulation (TENS) and laser therapy are part of these
      modalities, although little is known about their real efficacy in controlled
      studies. This research compared these two treatments in a sample of 18 patients
      with chronic TMD of muscular origin, divided into two groups (LASER and TENS).
      Treatment consisted of ten sessions, in a period of 30 days. Active range of
      motion (AROM), visual analogue scale (VAS) of pain and muscle (masseter and
      anterior temporalis) palpation were used for follow-up analysis. Data were
      analyzed by Friedman test and ANOVA for repeated measurements. Results showed
      decrease in pain and increase in AROM for both groups (p<0.05), and improvement
      in muscle tenderness for the LASER group. Authors concluded that both therapies
      are effective as part of TMD management and a cumulative effect may be
      responsible for the improvement. Caution is suggested when analyzing these
      results because of the self-limiting feature of musculoskeletal conditions like
      TMD.

PMID- 19089045
TI  - Fluoridation of the public water supply and prevalence of dental fluorosis in a
      peripheral district of the municipality of Bauru, SP.
AB  - OBJECTIVES: The objectives of this study were to assess the fluoride
      concentration in the public water supply and the prevalence of dental fluorosis
      in schoolchildren between 7 and 15 years old, living in a peripheral district of
      the municipality of Bauru. MATERIAL AND METHODS: For this, fifty two water
      samples were collected on three different days of one week. These samples were
      analyzed for fluoride by means of the ion-sensitive electrode method (Orion 9609)
      coupled to a potentiometer (Procyon, model 720). In this method, 1.0 mL of TISAB
      II (Orion) was added to 1.0 mL of the sample. For the epidemiological survey of
      fluorosis, 52 schoolchildren of both genders, aged between 7 and 15 were
      assessed, with prior authorization from their caretakers. Only one person
      examined the children, after supervised toothbrushing and drying with cotton wool
      rolls. The TF index was used. RESULTS: The fluoride concentrations in the water
      samples ranged from 0.62 to 1.20 mg/L, with a mean of 0.9 mg/L. The prevalence of
      dental fluorosis was 33%, with severity ranging from TF1 to TF4 (Kappa of 0.73
      and concordance of 83.33%). CONCLUSIONS: The results from the analysis of water
      samples indicated a fluoride concentration greater than recommended for Bauru.
      The fluorosis levels found were higher than expected for a peripheral district,
      in which water is one of the few sources of fluoride.

PMID- 19089046
TI  - Comparison of TW2 and TW3 skeletal age differences in a Brazilian population.
AB  - OBJECTIVE: The aim of this study was to determine the differences between the
      skeletal ages estimated by TW2 and TW3 methods through their RUS and Carpal
      systems. MATERIAL AND METHODS: A sample of two hundred and forty hand and wrist
      radiographs of male and female Brazilian children aged 84-199 months was
      evaluated by five observers. The Dunnet test was performed for statistical
      analysis. RESULTS: Results showed higher skeletal ages estimated by TW2RUS than
      TW3RUS and Carpal for both genders. For girls a statistically significant
      difference (p<0.05) was observed between TW2RUS and TW3RUS over the entire age
      range. For boys this difference was observed from 108 months onwards. In general
      RUS skeletal ages were higher than the chronological age and Carpal skeletal ages
      for both genders. The overestimation of chronological age was smaller for TW3RUS
      than for TW2RUS, and this last system showed a statistically significant
      difference regarding chronological age over the entire age range for girls,
      whereas for boys this difference was seen from 132 months onwards. For girls TW3
      RUS and Carpal showed a significant difference regarding chronological age in the
      oldest age groups; in boys TW3RUS did not show a significant difference regarding
      chronological age. For Carpal, these results were more variable. CONCLUSION: It
      seems reasonable to recommend the use of the TW3 system for the studied Brazilian
      population.

PMID- 19089047
TI  - Radiopacity of restorative materials using digital images.
AB  - The radiopacity of esthetic restorative materials has been established as an
      important requirement, improving the radiographic diagnosis. The aim of this
      study was to evaluate the radiopacity of six restorative materials using a direct
      digital image system, comparing them to the dental tissues (enamel-dentin),
      expressed as equivalent thickness of aluminum (millimeters of aluminum). Five
      specimens of each material were made. Three 2-mm thick longitudinal sections were
      cut from an intact extracted permanent molar tooth (including enamel and dentin).
      An aluminum step wedge with 9 steps was used. The samples of different materials
      were placed on a phosphor plate together with a tooth section, aluminum step
      wedge and metal code letter, and were exposed using a dental x-ray unit. Five
      measurements of radiographic density were obtained from each image of each item
      assessed (restorative material, enamel, dentin, each step of the aluminum step
      wedge) and the mean of these values was calculated. Radiopacity values were
      subsequently calculated as equivalents of aluminum thickness. Analysis of
      variance (ANOVA) indicated significant differences in radiopacity values among
      the materials (P<0.0001). The radiopacity values of the restorative materials
      evaluated were, in decreasing order: TPH, F2000, Synergy, Prisma Flow, Degufill,
      Luxat. Only Luxat had significantly lower radiopacity values than dentin. One
      material (Degufill) had similar radiopacity values to enamel and four (TPH,
      F2000, Synergy and Prisma Flow) had significantly higher radiopacity values than
      enamel. In conclusion, to assess the adequacy of posterior composite restorations
      it is important that the restorative material to be used has enough radiopacity,
      in order to be easily distinguished from the tooth structure in the radiographic
      image. Knowledge on the radiopacity of different materials helps professionals to
      select the most suitable material, along with other properties such as
      biocompatibility, adhesion and esthetic.

PMID- 19089048
TI  - Editorial.

PMID- 19089049
TI  - Healing of root perforations treated with Mineral Trioxide Aggregate (MTA) and
      Portland cement.
AB  - Fourteen root perforations were performed for microscopic evaluation of the
      repair of interradicular tissue in dogs' teeth. These perforations were
      accomplished at low-speed with a STP 58 bur at the cervical third of the mesial
      root toward the furcation under irrigation with saline solution, followed by
      immediate sealing with ProRoot MTA, MTA-Angelus and white Portland cement. The
      dogs were killed after 90 days, revealing good results. The Kruskal-Wallis test
      did not demonstrate any statistically significant difference. It was concluded
      that the three materials showed good sealing in mineralized tissue, with complete
      closure, and they were free of inflammation in most teeth.

PMID- 19089050
TI  - Performance of Brazilian and imported glass ionomer cements used in Atraumatic
      Restorative Treatment (ART) regarding microleakage in primary molars.
AB  - With the aim of assessing the performance of Brazilian and imported glass ionomer
      cements (GIC) with regard to microleakage, 40 primary molars received two
      standard class II cavity preparations with margins in enamel. Twenty cavities
      were filled with Brazilian materials (Vidrion R and Vidrion R(Caps)) and the
      other 20 cavities were filled with imported materials (Fuji IX and Fuji
      IX(GPFast) capsule). All fillings were performed by a single operator according
      to the manufacturer's instructions. Teeth were immersed in 0.5% methylene blue
      and half-sectioned. Three independent calibrated examiners assessed microleakage
      using scores (0-3). Data were submitted to the Kruskal-Wallis statistical test
      and Wilcoxon analysis. High microleakage indexes were verified for all ionomer
      cements: 59.5% of the samples restored with Vidrion R or Vidrion R(Caps) and
      83.4% of the samples restored with Fuji IX or Fuji IX(GPFast) capsule obtained
      the maximum score (3). The Brazilian ionomer cements presented less microleakage
      than imported cements, although this difference was only significant (p=0.003)
      among the encapsulated materials.

PMID- 19089051
TI  - Effect of betamethasone and diclofenac sodium on serum and tissue concentration
      of amoxicillin. In vivo study in rats.
AB  - OBJECTIVE: Antimicrobial agents in combination with anti-inflammatory drugs have
      been usually prescribed in both Medicine and Dentistry. However, few scientific
      reports support this clinical practice. The aim of this study was to evaluate the
      effect of betamethasone and diclofenac sodium on serum and tissue concentration
      of amoxicillin in rats. METHODS: Four polyurethane sponges were implanted in the
      back skin of 48 rats. After seven days the animals were divided into 6 groups
      (n=8). Group 1: amoxicillin (25 mg/kg); G2: diclofenac sodium (2.5 mg/kg); G3:
      betamethasone (0.1 mg/kg); G4: diclofenac sodium and amoxicillin; G5:
      betamethasone and amoxicillin; and G6: 0.9% sodium chloride solution (1.0 mL -
      control group). All drugs were administered in a single dose. After 90 minutes,
      the granulomatous tissues of each animal were surgically removed and weighed.
      Blood was collected from cervical plexus, centrifuged and 10microL of serum was
      placed on paper discs. In order to estimate amoxicillin concentration, serum and
      granulomatous tissues were separately submitted to microbiological assay, which
      used 10(8)cfu/mL of Staphylococcus aureus ATCC 25923 (penicillin-susceptible
      strain). After incubation (18 hours, 37 degrees C) the inhibition zones were
      measured and compared to a regression curve. RESULTS: No inhibition zones were
      observed for groups 2, 3 and 6. Tissue and serum concentrations of both G1
      (4.14microg/g and 2.06microg/mL, respectively) and G5 (3.87microg/g and
      1.70microg/mL, respectively) showed statistically significant differences
      (Kruskal-Wallis, p<0.05) in comparison to G4 (1.45microg/g and 0.41microg/mL,
      respectively). G1 and G5 did not differ significantly (p>0.05). CONCLUSION:
      Considering single doses, betamethasone did not interfere with amoxicillin levels
      but diclofenac sodium reduced both tissue and serum levels of amoxicillin in
      rats.

PMID- 19089052
TI  - Retrospective analysis of orthodontic treatment outcomes and its relation to
      postretention stability.
AB  - OBJECTIVE: The present study was designed to retrospectively evaluate Class I
      malocclusion cases treated with extraction of the four first premolars, aiming to
      establish the relationship between the quality of orthodontic treatment outcomes
      and the long-term occlusal stability. MATERIAL AND METHODS: The sample comprised
      94 patients of both genders, presenting Class I malocclusion, treated with
      extractions of the four first premolars and Edgewise mechanics. All the patients
      selected were whites, being 50 males and 44 females. The mean pretreatment age
      was 13.46 years (s.d. 1.8). The mean treatment time was 2.09 years (s.d. 0.58),
      the mean retention time was 1.63 years (s.d. 0.73) and the mean time of
      postretention evaluation was 5.31 years (s.d. 1.61). The dental casts were
      measured at pretreatment (T1), posttreatment (T2) and postretention (T3), by the
      PAR index and by the Little irregularity index, and the correction due to
      treatment (T1-2) and the change at the postretention period (T3-2) were
      calculated. The descriptive statistics was performed and the Pearson correlation
      coefficient was applied for the PAR and the Little indices in the total sample,
      among the times evaluated. RESULTS: The mean PAR reduction due to treatment was
      78.54%, and 66.6%, at the postretention stage related to pretreatment stage.
      Significant correlations were found for the PAR index at the times evaluated,
      except between T1 and T2 and between T1-2 and T3. In other words, the higher the
      treatment correction (T1-2), the lower the posttreatment PAR index (PAR T2) will
      be, and the higher will be the PAR change at the postretention period (PAR T3-2).
      Also, the higher the posttreatment PAR score (PAR T2), the higher will be the
      postretention PAR score (PAR T3). CONCLUSION: It was concluded that the quality
      of orthodontic treatment outcomes is not related to the long-term occlusal
      stability.

PMID- 19089053
TI  - Comparative evaluation of antimicrobial action of MTA, calcium hydroxide and
      Portland cement.
AB  - The present study aimed to evaluate and compare the antimicrobial effect of MTA
      Dentsply, MTA Angelus, Calcium Hydroxide and Portland cement. Four reference
      bacterial strains were used: Pseudomonas aeruginosa, Escherichia coli,
      Bacteroides fragilis, and Enterococcus faecalis. Plates containing Mueller-Hinton
      agar supplemented with 5% sheep blood, hemin, and menadione were inoculated with
      the bacterial suspensions. Subsequently, wells were prepared and immediately
      filled with materials and incubated at 37 degrees C for 48 hours under anaerobic
      conditions, except P. aeruginosa. The diameters of inhibition zones were
      measured, and data analyzed using ANOVA and the Tukey test with 1% level of
      significance. MTA Dentsply, MTA Angelus and Portland cement inhibited the growth
      of P. aeruginosa. Calcium Hydroxide was effective against P. aeruginosa and B.
      fragillis. Under anaerobic conditions, which may hamper the formation of reactive
      oxygen species, the materials failed to inhibit E. faecalis, and E. coli.

PMID- 19089054
TI  - Association of calcium hydroxide and metronidazole in the treatment of dog's
      teeth with chronic periapical lesion.
AB  - One of the primary objectives of endodontic treatment of teeth with pulp necrosis
      is the elimination of microorganisms from the root canal system, as effectively
      as possible, especially in cases with chronic periapical lesions. AIM: The
      purpose of this study was to analyze the response of the periapical tissue of
      dogs' teeth with chronic periapical lesions to endodontic treatment performed
      with utilization of metronidazole, calcium hydroxide, and an association of both
      as root canal dressings. METHODOLOGY: Forty root canals were submitted to
      pulpectomy and the root canals were kept exposed to the oral environment for 6
      months. Then, they were submitted to biomechanical preparation and divided into 4
      study groups with 10 specimens: group I - no root canal dressing; group II -
      calcium hydroxide; group III - metronidazole; group IV - calcium hydroxide
      associated to metronidazole. After 15 days, the root canals were filled with Fill
      Canal sealer. After 90 days, the animals were killed and the specimens processed
      for histological analysis. RESULTS: Calcium hydroxide dressing provided a
      significantly better outcome compared to other experimental groups (alpha =
      0.01). Also, the results of the association of metronidazole and calcium
      hydroxide were similar to those observed for the metronidazole group. The worst
      results were obtained by the no root canal dressing group. CONCLUSION: The use of
      metronidazole alone or associated with Calcium hydroxide, did not improve
      periapical healing when compared to Calcium hydroxide dressing.

PMID- 19089055
TI  - Evaluation of apical microleakage of teeth sealed with four different root canal
      sealers.
AB  - OBJECTIVES: To compare the apical sealing ability of four root canal sealers.
      MATERIAL AND METHODS: Forty extracted human maxillary canines were instrumented 1
      mm short of the anatomical apex and randomly assigned to four groups (n=10),
      according to the root canal sealer used for obturation: Endofill, AH Plus,
      EndoREZ and Epiphany. Root canals were obturated with gutta-percha points, except
      for the Epiphany group, in which resin points (Resilon) were used. The teeth were
      immersed in India ink for seven days and clarified using methyl salicylate. The
      extent of apical dye penetration was measured with a measuroscope in all aspects
      of the canal. RESULTS: AH Plus (0.02 mm +/- 0.07), Epiphany (0.00 mm +/- 0.00)
      and EndoREZ (0.32 mm +/- 0.62) did not differ statistically to each other
      (p>0.01). EndoFill presented the highest dye penetration mean (0.83 mm +/- 0.73)
      and was statistically different from the other sealers (p<0.01). CONCLUSION: The
      resin-based root canal sealers presented lesser apical microleakage than the zinc
      oxide and eugenol based sealer. No statistical differences were observed among
      resin based sealers.

PMID- 19089056
TI  - Fluoride level in public water supplies of cities from the northwest region of
      Sao Paulo State, Brazil.
AB  - It may be difficult for small and medium cities to obtain information about the
      fluoride content of public water, because of the lack of equipments and
      technicians. This study aimed to analyze the fluoride levels of the water
      supplied by the public treatment stations of 40 cities situated in the northwest
      region of Sao Paulo State, during a period of 6 months, to verify if fluoridation
      occurs in a continuous manner and if the fluoride levels are within the
      recommended. Maps of the water distribution system were obtained from the water
      treatment companies and utilized to randomize the addresses of the collection
      sites, so that they included all regions with treated water sources. One water
      sample by month was collected and analyzed in duplicate using an ion-specific
      electrode. Samples with 0.6 to 0.8 mgF/L were considered acceptable. In the 38
      cities that regularly provided the samples in the 6 months of the study, water
      from 144 collection sites was collected and a total of 864 samples were analyzed,
      of which 61.81 percent were classified as unacceptable. It was observed that 33
      cities performed fluoridation but in 78.79 percent of these cities there were
      variations in the fluoride level among the sites and in the same site during the
      period of study. One can conclude that most of these cities do not control the
      fluoride levels in the public water, since fluoridation occurs in a discontinuous
      manner and in most of the situations not within the recommended concentrations.

PMID- 19089057
TI  - Influence of different methods of cervical flaring on establishment of working
      length.
AB  - OBJECTIVE: To investigate the influence of three different rotary systems for
      cervical flaring on establishment of the real working length. MATERIAL AND
      METHODS: Thirty mandibular first molars were submitted to conventional endodontic
      access and initial working length measurement, followed by irrigation/suction of
      the pulp chamber with 5% sodium hypochlorite. Teeth were randomly divided into 3
      groups (n=10) and cervical flaring of the mesiobuccal canals were performed using
      one of the following instrument systems: Group 1 - Gates-Glidden burs; Group 2 -
      Orifice Openers; Group 3 - La Axxess system. Two subsequent numbers of
      instruments of each rotary system were used and the final working length was
      recorded. A digital calyper was used to record the working length, in
      millimeters, to investigate a possible discrepancy between initial and final
      measurements. RESULTS: Analysis of variance (Anova) na Tukey test revealed
      statistical difference between Group 1 and Groups 2 and 3 (p pound 0.05).
      CONCLUSIONS: All groups presented shorter working length after cervical flaring;
      groups prepared with instruments La Axxes and Orifice Opener presented the best
      results among the systems studied.

PMID- 19089058
TI  - Histomicrobiologic aspects of the root canal system and periapical lesions in
      dogs' teeth after rotary instrumentation and intracanal dressing with Ca(OH)2
      pastes.
AB  - OBJECTIVE: The purpose of this study was to evaluate the distribution of
      microorganisms in the root canal system (RCS) and periapical lesions of dogs'
      teeth after rotary instrumentation and placement of different calcium hydroxide
      [Ca(OH)2]-based intracanal dressings. MATERIALS AND METHODS: Chronic periapical
      lesions were experimentally induced in 80 premolar roots of four dogs.
      Instrumentation was undertaken using the ProFile rotary system and irrigation
      with 5.25% sodium hypochlorite. The following Ca(OH)2-based pastes were applied
      for 21 days: group 1 - Calen (n=18); group 2 - Calen+CPMC (n=20); group 3 -
      Ca(OH)2 p.a. + anaesthetic solution (n=16) and group 4 - Ca(OH)2 p.a.+ 2%
      chlorhexidine digluconate (n=18). Eight root canals without endodontic treatment
      constituted the control group. Histological sections were obtained and stained
      with Brown & Brenn staining technique to evaluate the presence of microorganisms
      in the main root canal, ramifications of the apical delta and secondary canals,
      apical cementoplasts, dentinal tubules, areas of cemental resorption and
      periapical lesions. The results were analyzed statistically by the Mann-Whitney U
      test (p<0.05). RESULTS: The control group showed the highest prevalence of
      microorganisms in all sites evaluated. Gram-positive cocci, bacilli and filaments
      were the most frequent morphotypes. Similar microbial distribution patterns in
      the RCS and areas of cementum resorption were observed in all groups (p>0.05).
      The percentage of RCS sites containing microorganisms in groups 1, 2, 3, 4 and
      control were: 67.6%, 62.5%, 78.2%, 62.0% and 87.6%, respectively. CONCLUSION: In
      conclusion, the histomicrobiological analysis showed that the rotary
      instrumentation and the different calcium hydroxide pastes employed did not
      effectively eliminate the infection from the RCS and periapical lesions. However,
      several bacteria seen in the histological sections were probably dead or were
      inactivated by the biomechanical preparation and calcium hydroxide-based
      intracanal dressing.

PMID- 19089059
TI  - Fluoride concentration in water at the area supplied by the Water Treatment
      Station of Bauru, SP.
AB  - OBJECTIVE: To analyze the fluoride concentration in the public water supply at
      the area supplied by the Water Treatment Station of Bauru and classify the
      samples as acceptable or unacceptable according to the fluoride concentration.
      MATERIAL AND METHODS: Samples were collected from 30 areas at two periods,
      October 2002 and March 2003. The fluoride concentration in the samples was
      determined in duplicate, using an ion sensitive electrode (Orion 9609) connected
      to a potentiometer (Procyon, model 720). Samples with fluoride concentration
      ranging from 0.55 to 0.84 mg F/L were considered acceptable, and those whose
      concentration was outside this range as unacceptable. Data were analyzed by
      descriptive statistics. RESULTS: The fluoride concentration of the water samples
      varied between 0.31 and 2.01 mg F/L. Nearly 56% of the samples were classified as
      acceptable. CONCLUSION: The variations in fluoride concentration at the area
      supplied by the Water Treatment Station reinforce the need of constant monitoring
      for maintenance of adequate fluoride levels in the public water supply.

PMID- 19089060
TI  - Development of periradicular lesions in normal and diabetic rats.
AB  - Evidence suggests that diabetic patients are more significantly affected by
      problems of endodontic origin. This study sought to radiographically and
      histologically examine the development of periradicular inflammation in control
      and in diabetic rats after induction of pulpal infection. The pulps of the
      mandibular first molars of normal and streptozotocin-induced diabetic rats were
      exposed and left in contact with their oral cavities for 21 and 40 days.
      Afterwards, the animals were sacrificed, the mandibles were surgically removed,
      fixed in formalin and then radiographed in a standardized position. The
      radiographic images of the periradicular lesions were scanned and computerized
      images were evaluated for the total area of the lesions using a specific
      software. Representative specimens were also prepared for histopathological
      analysis. Radiographic analysis revealed that diabetic rats presented
      significantly larger periradicular lesions when compared with control rats,
      regardless of the experimental period (p<0.05). Histopathological examination of
      representative specimens revealed larger periradicular lesions and more severe
      inflammatory exudate in the group of diabetic rats when compared with the control
      group. Data from the present study indicated that diabetic rats can be more prone
      to develop large periradicular lesions, possibly due to reduction in the defense
      ability against microbial pathogens.

PMID- 19089061
TI  - Histological analysis of the biocompatibility of three different calcium
      hydroxide-based root canal sealers.
AB  - OBJECTIVE: To histologically evaluate the behavior of the subcutaneous tissue of
      rats after placement of polyethylene tubes filled with calcium hydroxide-based
      root canal sealers (Sealapex, Apexit e Sealer 26). STUDY DESIGN: The study
      employed 60 rats, which were divided into eight groups, being four experimental
      groups with 10 rats each, and four control groups with five rats. Analysis was
      conducted at 48 hours, 7, 21 and 60 days. RESULTS: Histological analysis revealed
      that all sealers were irritant; however, the intensity varied between each sealer
      and as a function of time. At the initial periods (48 hours and seven days), all
      materials demonstrated similar outcomes, with inflammatory reaction from severe
      to moderate, respectively. At the final periods (21 and 60 days), the tissue
      reactions to the implants containing Sealapex displayed an active status yet with
      regression, compared to the Apexit and Sealer 26. The control groups exhibited
      less inflammatory cells than the experimental groups, keeping a reaction status
      with regression. CONCLUSIONS: The results achieved in this study revealed that
      the Sealapex sealer was the most compatible, followed by Apexit and Sealer 26.

PMID- 19089062
TI  - Fluoride intake from drinking water and dentifrice by children living in a
      tropical area of Brazil.
AB  - OBJECTIVE: To assess fluoride (F-) intake from water and toothpaste by children
      aged 18 to 36 months and to monitor the F- concentrations in the drinking water
      system in a tropical city of Brazil. METHODS: Children (n=58) aged 18-36 months,
      all lifetime residents of Penedo, state of Alagoas, Brazil, participated in this
      study. Water F- analyses were carried out in 7 different occasions at least a
      week apart. For 2 days all the water drunk by each child was accounted for.
      Fluoride intake from water for each child was estimated using the mean F-
      concentration of water in 7 different occasions. Fluoride intake from toothpaste
      was estimated by subtracting the recovered post-brushing F- from the original
      amount placed in the toothbrush. The F- intake from water and toothpaste was
      estimated by dividing the total amount of F- ingested by the weight of each
      child. RESULTS: The mean F- concentration in the drinking water was 0.94 ppm
      (mean range 0.78-1.1 ppm), which is above the 0.7 ppm recommended for this area
      of Brazil. Mean total F- intake from water and toothpaste was 0.128 mg F-/Kg Body
      Weight/day. The daily means of F- intake from water and toothpaste were 0.021 and
      0.107 mg F-/Kg Body Weight, respectively. Ninety six percent of children showed F
      intake above 0.07 mg F-/Kg Body Weight/day. CONCLUSIONS: Children in Penedo are
      at risk for developing dental fluorosis due to high F- intake from fluoridated
      toothpastes. Water fluoridation showed low contribution to the total F- intake.
      However, high water F- concentrations in the water indicate the need of
      surveillance of the artificial water fluoridation system.

PMID- 19089063
TI  - Pain characteristics of temporomandibular disorder: a pilot study in patients
      with cervical spine dysfunction.
AB  - OBJECTIVE: The purpose of the present pilot study was to describe pain complaints
      of TMD patients and cervical spine dysfunction. METHODS: Fourteen women with
      myogenous TMD, cervical motion limitation and rotation of at least one of the
      three first cervical vertebrae evidenced by radiographic examination participated
      in this study. The multidimensional pain evaluation was accomplished by a
      Brazilian version of the McGill Pain Questionnaire. RESULTS: The results showed
      that the most painful body site mentioned was cervical spine, followed by
      scapular region and temporomandibular joint. More than half of the volunteers
      reported temporal pain pattern as rhythmic, periodic and, or still, intermittent.
      The majority of the patients classified the pain intensity assessed at the moment
      of the evaluation as mild to discomforting. Absolute agreement was not observed
      among volunteers regarding word dimensions used to describe their pain, although
      a great number of patients chose the descriptor related to tension as the better
      expression to describe their painful complaint. CONCLUSION: Pain characteristics
      of TMD patients with cervical spine dysfunction showed cervical spine as a common
      painful region reported and words related to affective and emotional dimensions
      of pain perception can be used by these patients to qualify their pain complain.

PMID- 19089064
TI  - Occurrence of Actinobacillus actinomycetemcomitans in patients with chronic
      periodontitis, aggressive periodontitis, healthy subjects and children with
      gingivitis in two cities of the state of Sao Paulo, Brazil.
AB  - The aim of this study was to determine the frequency of isolation of
      Actinobacillus actinomycetemcomitans (Aa) in 100 patients with chronic
      periodontitis, 14 patients with aggressive periodontitis, 142 pre-school children
      with gingivitis and 134 periodontally healthy subjects. Samples of subgingival
      plaque were taken using sterilized paper points introduced into periodontal
      pockets or gingival crevice for 60 seconds and inoculated on TSBV agar, which was
      incubated under anaerobiosis at 37 degrees C, for 4 days. Microbial
      identification was performed through biochemical methods and morphocellular and
      morphocolonial analysis. Aa was detected in 40.3% of healthy subjects, 68% of
      patients with chronic periodontitis, 92.86% of patients with aggressive
      periodontitis and 40.14% of children with gingivitis. The rate of recovery of Aa
      in the tested human groups proved to be higher than previously reported and in
      agreement with participation of this facultative anaerobe as a member of native
      microbiota of the periodontium and its relation with aggressive and chronic
      periodontitis in Brazil.

PMID- 19089065
TI  - Pattern of disocclusion in patients with complete cleft lip and palate.
AB  - OBJECTIVE: To analyze the pattern of disocclusion during excursive mandibular
      movements and presence or absence of occlusal interferences and occlusal
      pathologies (gingival recession and abfraction). METHOD: Examination of 120
      individuals divided into two groups, as follows: Group 1 - 90 patients with
      complete cleft lip and palate (study group), subdivided into 30 patients with
      complete left unilateral cleft lip and palate, 30 patients with complete right
      unilateral cleft lip and palate and 30 patients with complete bilateral cleft lip
      and palate; Group 2 - 30 individuals without clefts (control group). RESULTS:
      58.8% of patients in Group 1 presented unilateral or bilateral canine guidance,
      26.6% presented unilateral or bilateral group function and 54.4% presented
      lateral movements through the posterior teeth. Regarding protrusive movements,
      80% presented anterior guidance and 20% presented posterior guidance. In Group 2,
      69.6% of individuals presented unilateral or bilateral canine guidance, 43.2%
      presented unilateral or bilateral group function and only 13.3% presented lateral
      movements through the posterior teeth; 3.4% presented protrusion through the
      posterior teeth. CONCLUSIONS: There was no difference in the pattern of
      disocclusion between subgroups of patients with clefts. Group 2 presented
      predominance of bilateral group function, whereas Group 1 presented a higher
      prevalence of posterior guidance during lateral movements. Protrusion occurred
      primarily through anterior guidance in Group 2 and through the posterior teeth in
      Group 1. There was high prevalence of occlusal interferences at the molar area
      for both groups, yet with no correlation with occlusal pathologies (recession and
      abfraction).

PMID- 19089066
TI  - Antiplaque and antigingivitis effects of a gel containing Punica granatum Linn
      extract: a double-blind clinical study in humans.
AB  - OBJECTIVES: The antiplaque and antigingivitis effects of a gel containing 10%
      Punica granatum Linn extract were evaluated using a 21-day partial-mouth
      experimental model of gingivitis. METHODS: 23 volunteers participated in this
      cross-over, double-blind study, carried out in 2 phases of 21 days each. For each
      period of the experiment, an acrylic toothshield was made for each volunteer to
      carry the test or placebo gel as well as to avoid brushing of the 4 experimental
      teeth (posterior teeth in the lower left quadrant). The subjects were randomly
      assigned to use either the placebo gel (control group) or the test gel
      (experimental group) and were instructed to brush the remaining teeth normally 3
      times a day. On days 0 and 21, the visible plaque index (VPI) and gingival
      bleeding index (GBI) were recorded. RESULTS: The results did not show
      statistically significant difference between control and experimental groups for
      either of the indices (VPI and GBI). CONCLUSION: The gel containing 10% Punica
      granatum Linn extract was not efficient in preventing supragingival dental plaque
      formation and gingivitis.

PMID- 19089067
TI  - Impact of the bitewing radiography exam inclusion on the prevalence of dental
      caries in 12-year-old students in the city of Franca, Sao Paulo, Brazil.
AB  - INTRODUCTION: The pattern of development of carious lesions has changed. The
      carious lesion has been progressive and reaches the dentin without showing
      alterations in the clinical aspects. OBJECTIVES: To determine the prevalence of
      caries in 12-year-old students in the city of Franca - Sao Paulo, Brazil, during
      the year of 2003, and to evaluate the additional value of bitewing radiograph to
      detect hidden carious lesions in permanent molar dentin. MATERIALS AND METHODS: A
      probabilistic sample composed of two hundred and fifty six (256) students, from
      public and private schools, was submitted to a cross-sectional study through
      examination by a calibrated examiner, in order to detect the caries prevalence,
      using the methodology recommended by the World Health Organization (WHO). For 66%
      of the sample, bitewing radiographs of the permanent molar region were obtained.
      The images were analyzed by a calibrated examiner, who established the presence
      of hidden caries in teeth with radiolucency in dentin, yet considered healthy in
      the epidemiological survey. RESULTS: The prevalence of dental caries in
      epidemiological exam without (WHO) and with (WHO/R) the inclusion of hidden
      caries lesion was 54% and 64%, and the DMFT index was 1.73 and 1.92 respectively.
      CONCLUSION: Utilization of the method of bitewing radiographic diagnosis
      significantly increased (p<0.001) the prevalence of caries in the studied
      population.

PMID- 19089068
TI  - Elimination of intracanal infection in dogs' teeth with induced periapical
      lesions after rotary instrumentation: influence of different calcium hydroxide
      pastes.
AB  - The aim of this study was to evaluate the antiseptic efficacy of rotary
      instrumentation associated with calcium hydroxide-based pastes prepared with
      different vehicles and antiseptics. Chronic periapical lesions were
      experimentally induced in 72 premolar root canals of four dogs. Under controlled
      asepsis, after initial microbiological sampling (A1), the root canals were
      instrumented using the ProFile system in conjunction with 5.25% sodium
      hypochlorite and the intracanal medication was placed. Four experimental groups
      were formed according to the pastes used: group 1- Calen (n=18), group 2-
      Calen+CPMC (n=20), group 3- Ca(OH)(2) p.a.+ anaesthetic solution (n=16) and group
      4- Ca(OH)(2) p.a.+ 2% chlorhexidine digluconate (n=18). After 21 days, the pastes
      were removed; the canals were emptied and 96 hours later a second microbiological
      sample was obtained (A2). The incidence of positive microbiological cultures and
      the number of cfus in stages A1 and A2 were compared statistically by the
      Wilcoxon test while the influence of the different treatments in intracanal
      infection was evaluated by Kruskal-Wallis test at 5% significance level (p<0.05).
      Large numbers of strict and facultative anaerobes, and viridans group
      streptococci were found in 100% of root canals of A1 samples. Among A2 samples,
      all treatments showed significant reduction of cfus and positive cultures
      (p<0.05), but only groups 3 and 4 showed 100% of root canals free of
      microorganisms. Rotary instrumentation plus NaOCl 5.25% associated with
      intracanal medication produced a drastic reduction or elimination of intracanal
      microbiota, whose performance was not influenced by the nature of the vehicle or
      the antiseptic added to the Ca(OH)(2) p.a.

PMID- 19089069
TI  - Morphologic and morphometric analysis of the root canal apical third cleaning
      after biomechanical preparation using 3.3% Ricinus communis detergent and 1%
      NaOCl as irrigating solutions.
AB  - This study evaluated, by morphologic and morphometric analyses, the cleaning of
      apical third of root canals instrumented with nickel-titanium rotary files using
      different irrigating solutions. Twenty-seven single-rooted mandibular premolars
      were assigned to three groups (n=9), according to the irrigating solution used:
      Group I, distilled and deionized water; Group II, 1% NaOCl; and Group III, 3.3%
      Ricinus communis detergent. Biomechanical preparation was performed with Protaper
      Plusa nickel-titanium files as follows: S1, SX and S2 at the cervical and middle
      thirds, and 25/02, 25/04, 25/06, 30/02, 30/04 and 30/06 to complete the
      instrumentation, operating at 1 mm from the root apex. Irrigation was done at
      each file change with 2 mL of irrigating solution, totalizing 20 mL for each
      tooth. After biomechanical preparation, the apical thirds were serially sectioned
      and histologically processed. The cross-sections were examined by an optical
      microscope (X40) connected to a computer. The images were captured and analyzed
      using a computer software and submitted to morphometric analysis with aid of a
      grid. The percentage of debris remaining at the apical third was calculated. Data
      were submitted to statistical analysis by ANOVA and Tukey test. The results
      showed no statistically significant difference (p>0.01) between the groups
      irrigated with 1% NaOCl and 3.3% Ricinus communis detergent, which presented the
      lowest percentage of debris at the apical third, 8.49% and 10.11%, respectively.
      The group irrigated with distilled and deionized water had the highest percentage
      of debris (15.58%) and was statistically different from the other groups
      (p<0.01). It may be concluded that 3.3% Ricinus communis detergent and 1% NaOCl
      had similar cleaning effectiveness on removal of debris from root canals.

PMID- 19089070
TI  - Radiographic study of the prevalence of apical periodontitis and endodontic
      treatment in the adult population of Sao Luis, MA, Brazil.
AB  - This study investigated the prevalence of apical periodontitis (AP) and its
      association with endodontically treated teeth in residents of Sao Luis, MA,
      Brazil. Two-hundred complete series of periapical radiographs taken over a 10
      year period (1993-2003) were retrieved from the files of four prosthesists and
      five periodontists. The Periapical Index (PAI) was used and the age range, sex,
      tooth groups, location and association with endodontic treatment (ET) were also
      analyzed. The Cohen Kappa and Chi-square tests were used for statistical
      analysis. Out of 200 patients, 135 presented at least one case of AP, which
      corresponds to a prevalence of 67.5%. Of the 5008 teeth examined, 296 had AP and
      553 had ET. Therefore, considering the total number of teeth, AP and ET
      prevalences were 5.9% and 11%, respectively. Of the 553 endodontically treated
      teeth, 235 (42.5%) were associated with AP. Chi-square test showed a strong
      correlation between AP and ET (p<0.05). The 40-year-old age group was
      significantly the most prevalent (p<0.05). There was no association between AP
      and patient's sex (p>0.05). The maxillary incisors were the most affected group
      of teeth (p<0.05). AP had predilection for the maxilla and was strongly
      associated with endodontically treated teeth (p<0.05). The prevalence of apical
      periodontitis and endodontically treated teeth with AP was high and similar to
      the results of studies performed in other countries.

PMID- 19089071
TI  - Evaluation of the surface hardness of composite resins before and after polishing
      at different times.
AB  - PURPOSE: The aim of this study was to evaluate the surface hardness of six
      composite resins: Revolution, Natural Flow, Fill Magic Flow, Flow-it!
      (flowables), Silux Plus (microfilled) and Z100 (minifilled) before and after
      polishing at different times. MATERIALS AND METHODS: For this purpose, 240
      specimens (5mm diameter, 1.4mm high) were prepared. Vickers hardness was
      determined before and after polishing at different times: immediately, 24h, 7 and
      21 days after preparation of the samples. Statistical analysis was performed by
      ANOVA and Tukey test. RESULTS: There was no difference in the hardness of
      flowable resins, which had lower hardness than the minifilled resin. The
      minifilled resin showed the highest surface hardness as compared to the other
      materials (p<0.01). All materials exhibited higher hardness after polishing,
      being more evident after 7 days. CONCLUSION: It may be concluded that, regardless
      of the composite resin, surface hardness was considerably increased when
      polishing was delayed and performed 1 week after preparation of the samples.

PMID- 19089072
TI  - Airpolishing effect on bovine enamel and the posterior remineralizing effect of
      saliva. An in vitro study.
AB  - PURPOSE: The aim of the present study was to evaluate the alterations of surface
      microhardness and wear caused by the sodium bicarbonate jet on bovine enamel and
      the further remineralizing effect of artificial saliva. METHODS: Fifteen enamel
      samples (4,0mm x 4,0mm) were used, which constituted the groups: no treatment
      (MI); treatment with sodium bicarbonate jet (MII and DI); treatment with sodium
      bicarbonate jet and immersion in saliva for one hour (MIII and DII), 24 hours
      (MIV and DIII) and 7 days (MV and DIV). Microhardness tests were carried out
      using a microdurometer in groups M and wear tests by a rugosimeter in groups D.
      The data were assessed by the one criterion variance analysis and Tukey test.
      RESULTS: The mean value of microhardness, in KHN, in groups MI, MII, MIII, MIV
      and MV were 359,80; 335,46; 369,20; 377,73 and 341,86, respectively, whereas the
      mean values in microm, of wear for group DI, DII, DIII and DIV were 0,564; 0,519;
      0,441 and 0,428, respectively. CONCLUSIONS: The sodium bicarbonate jet caused a
      wear and a reduction in microhardness on the enamel surface; saliva promoted the
      recovery of initial condition surface microhardness and reduced the wear; the
      repairing effect of saliva on the surface microhardness alterations occurred
      within one hour of treatment, having no significant statistical difference from
      the effect obtained in 24 hours; the best saliva repairing effect on the wear
      occurred with treatment of 24 hours.

PMID- 19089073
TI  - Tenascin and fibronectin in pleomorphic adenoma of the salivary gland.
AB  - OBJECTIVES: To analyze the expression and distribution pattern of extracellular
      matrix components in pleomorphic adenomas of the major and minor salivary glands
      and to compare the morphological findings of these tumors with the
      immunohistochemical expression, considering the different types of stroma
      predominating in each case. METHODS AND RESULTS: The expression of tenascin (TN)
      and fibronectin (FN) was analyzed in 23 cases of pleomorphic adenomas, 11 major
      and 12 minor salivary gland tumors, by the streptavidin-biotin method using anti
      tenascin and anti-fibronectin antibodies. In addition, the immunohistochemical
      results were correlated with the morphological findings of the lesions. All cases
      analyzed were immunoreactive for the antibodies used. Fibronectin showed strong
      labeling in fibrous and chondroid stroma, while labeling was weak in hyaline and
      myxoid stroma. Tenascin expression was more intense in fibrous and chondroid
      stroma and moderate in hyaline and myxoid stroma. CONCLUSIONS: No difference in
      the expression of these proteins was observed between major and minor salivary
      gland tumors.

PMID- 19089074
TI  - Effect of post-polymerization heat treatments on the cytotoxicity of two denture
      base acrylic resins.
AB  - INTRODUCTION: Most denture base acrylic resins have polymethylmethacrylate in
      their composition. Several authors have discussed the polymerization process
      involved in converting monomer into polymer because adequate polymerization is a
      crucial factor in optimizing the physical properties and biocompatibility of
      denture base acrylic resins. To ensure the safety of these materials, in vitro
      cytotoxicity assays have been developed as preliminary screening tests to
      evaluate material biocompatibility. (3)H-thymidine incorporation test, which
      measures the number of cells synthesizing DNA, is one of the biological assays
      suggested for cytotoxicity testing. AIM: The purpose of this study was to
      investigate, using (3)H-thymidine incorporation test, the effect of microwave and
      water-bath post-polymerization heat treatments on the cytotoxicity of two denture
      base acrylic resins. MATERIALS AND METHODS: Nine disc-shaped specimens (10 x 1
      mm) of each denture base resin (Lucitone 550 and QC 20) were prepared according
      to the manufacturers' recommendations and stored in distilled water at 37 degrees
      C for 48 h. The specimens were assigned to 3 groups: 1) post-polymerization in a
      microwave oven for 3 min at 500 W; 2) post-polymerization in water-bath at 55
      degrees C for 60 min; and 3) without post-polymerization. For preparation of
      eluates, 3 discs were placed into a sterile glass vial with 9 mL of Eagle's
      medium and incubated at 37 degrees C for 24 h. The cytotoxic effect of the
      eluates was evaluated by (3)H-thymidine incorporation. RESULTS: The results
      showed that the components leached from the resins were cytotoxic to L929 cells,
      except for the specimens heat treated in water bath (p<0.05). Compared to the
      group with no heat treatment, water-bath decreased the cytotoxicity of the
      denture base acrylic resins. CONCLUSION: The in vitro cytotoxicity of the tested
      denture base materials was not influenced by microwave post-polymerization heat
      treatment.

PMID- 19089075
TI  - Influence of a cobalt-chromium metal framework on surface roughness and Knoop
      hardness of visible light-polymerized acrylic resins.
AB  - Although visible light-polymerized acrylic resins have been used in removable
      partial dentures, it is not clear whether the presence of a metal framework could
      interfere with their polymerization, by possibly reflecting the light and
      affecting important properties, such as roughness and hardness, which would
      consequently increase biofilm accumulation. The aim of this study was to compare
      the roughness and Knoop hardness of a visible light-polymerized acrylic resin and
      to compare these values to those of water-bath- and microwave-polymerized resins,
      in the presence of a metal framework. Thirty-six specimens measuring 30.0 x 4.0
      +/- 0.5 mm of a microwave- (Onda Cryl), a visible light- (Triad) and a water-bath
      polymerized (Classico) (control) acrylic resins containing a cobalt-chromium
      metal bar were prepared. After processing, specimens were ground with 360 to 1000
      grit abrasive papers in a polishing machine, followed by polishing with cloths
      and 1-microm diamond particle suspension. Roughness was evaluated using a
      profilometer (Surfcorder SE 1700) and Knoop hardness (Kg/mm(2)) was assayed using
      a microhardness tester (Shimadzu HMV 2000) at distances of 50, 100, 200, 400 and
      800 microm from the metal bar. Roughness and Knoop hardness means were submitted
      to two-way ANOVA and compared by Tukey and Kruskal Wallis tests at a 5%
      significance level Statistically significant differences were found (p<0.05) for
      roughness and Knoop hardness, with light-polymerized resin presenting the highest
      values (Ra = 0.11 microm and hardness between 20.2 and 21.4 Kg/mm(2)). Knoop
      values at different distances from the metal bar did not differ statistically
      (p>0.05). Within the limitations of this in vitro study, it was concluded that
      the presence of metal did not influence roughness and hardness values of any of
      the tested acrylic resins.

PMID- 19089076
TI  - Histomorphometric analysis of pure titanium implants with porous surface versus
      rough surface.
AB  - The purpose of this study was to analyze the bone repair around commercially pure
      titanium implants with rough and porous surface, fabricated using powder
      metallurgy technique, after their insertion in tibiae of rabbits. Seven male
      rabbits were used. Each animal received 3 porous-surface implants in the left
      tibia and 3 rough-surface implants in the right tibia. The rabbits were
      sacrificed 4 weeks after surgery and fragments of the tibiae containing the
      implants were submitted to histological and histomorphometric analyses to
      evaluate new bone formation at the implant-bone interface. Means (%) of bone
      neoformation obtained in the histomorphometric analysis were compared by
      Student's t-test for paired samples at 5% significance level.. The results of the
      histological analysis showed that osseointegration occurred for both types of
      implants with similar quality of bone tissue. The histomorphometric analysis
      revealed means of new bone formation at implant-bone interface of 79.69 +/- 1.00%
      and 65.05 +/- 1.23% for the porous- and rough-surface implants, respectively.
      Statistically significant difference was observed between the two types of
      implants with respect to the amount new bone formation (p<0.05). In conclusion,
      the porous-surface implants contributed to the osseointegration because they
      provide a larger contact area at implant-bone interface.

PMID- 19089077
TI  - Influence of calcium hydroxide points on the quality of intracanal dressing
      filling.
AB  - PURPOSE: The aim of this study was to evaluate, in vitro, the quality of calcium
      hydroxide [Ca(OH)(2)] paste filling (Ultracal, Ultradent) associated or not with
      Ca(OH)(2)-containing gutta-percha points (Calcium Hydroxide Plus Points, Roeko)
      in curved root canals. MATERIAL AND METHODS: One hundred and twenty roots of
      extracted human teeth, randomly divided into three curvature ranges (mild - 0 to
      14 degrees; moderate - 15 degrees to 29 degrees; severe - >30 degrees) were used.
      After chemomechanical preparation, the roots were assigned to 4 groups (n=30),
      according to the technique of intracanal dressing placement: group 1 - Ca(OH)(2)
      paste was applied with a lentulo spiral; group 2 - Ca(OH)(2) paste was applied
      with a lentulo spiral and a Ca(OH)(2) point was inserted into the canal; group 3 
      Ca(OH)(2) paste was applied with a Navitip tip (supplied with Ultracal system);
      group 4 - Ca(OH)(2) paste was applied with a Navitip tip and a Ca(OH)(2) point
      was inserted into the canal. The roots were cleared and the quality of apical
      third filling was assessed by a calibrated experienced examiner. The specimens
      were examined under stereomicroscopy and scored 1 to 4 (i.e., from inadequate to
      complete root canal filling). The results were analyzed statistically by ANOVA
      and Duncan's post hoc test at 5% significance level. RESULTS: There were no
      statistically significant differences (p>0.05) among the curvature degrees in
      groups 1, 3 and 4. Severely curved roots in group 2 presented bordering
      significance (p=0.05). The groups that associated the use of Ca(OH)(2) paste and
      points (2 and 4) showed better apical filling than the other groups, but this
      difference was statistically significant (p<0.001) only for roots with severe
      curvature. CONCLUSION: According to the results of this study, the curvature
      degree did not influence the quality of filling. The techniques that used
      Ca(OH)(2)-containing gutta-percha points yielded better filling of the apical
      third in roots with severe curvature.

PMID- 19089078
TI  - International symposium of Atraumatic Restorative Treatment: proceedings of the
      symposium held on 4-5 June 2004 at Bauru Dental School, Bauru, Sao Paulo, Brazil.

PMID- 19089079
TI  - Advances in glass-ionomer cements.
AB  - This article describes the properties, advances and shortcomings of glass-ionomer
      cement as a restorative material. The adhesion of glass-ionomer to tooth
      structure is less technique sensitive than composite resins and its quality
      increases with time. Therefore glass-ionomer might turn out to the more reliable
      restorative material in minimal invasive dentistry based on adhesive techniques.

PMID- 19089080
TI  - Clinical evaluation of glass-ionomer cement restorations.
AB  - This article mentions the general structure, properties and clinical performance
      of conventional and resin-modified glass-ionomer cements, focusing on adhesion,
      caries inhibition effect and recommendations of their use.

PMID- 19089081
TI  - Clinical trials with Atraumatic Restorative Treatment (ART) in deciduos and
      permanent teeth.
AB  - This paper presents a review of the literature on clinical trials with Atraumatic
      Restorative Treatment. The available scientific literature is encouraging in
      terms of management of dental caries by this approach, especially for one-surface
      lesions. The steps of ART are described and the crucial points highlighted. The
      incorporation of ART into primary health care services, as Family Health Program 
      PSF, was considered.

PMID- 19089082
TI  - Research proposal: quantitative and qualitative evaluation of the ART in infants.
AB  - The accomplishment of the Atraumatic Restorative Treatment (ART) approach during
      the early childhood may represent a remarkably less traumatic and less expensive
      therapeutic choice. The purpose of this study is to investigate the mothers'
      perceptions about the ART technique in the oral health/disease process of their
      children diagnosed with Early Childhood Caries (ECC), and to evaluate the
      clinical performance of the atraumatic restorations placed in these children at
      six-, twelve- and twenty-four-month intervals.

PMID- 19089083
TI  - Research proposal: evaluation of ART in adult patients.
AB  - The primary objective of the Atraumatic Restorative Treatment (ART) is to reduce
      the indication of tooth extraction by means of a low-cost technique. Considering
      the difficulties of Brazilian public services to meet the demand of care of the
      low-income population, with lack of care to the adult population, which usually
      receives only emergency care, the aim of this study is to assess the performance
      of high-viscosity glass ionomer cements accomplished by the modified atraumatic
      restorative treatment in one- and multiple-surface cavities, compared to the
      conventional restorative approach. It will be analyzed the clinical performance
      of the materials; cost (material and human resources); patient satisfaction with
      the treatment received; and preventive effect of treatment.

PMID- 19089084
TI  - Research proposal: evaluation of the ART approach in elderly patients.
AB  - With the increase of life expectancy in the world's population, oral health care
      of elderly people has attracted considerably more attention over the last years.
      Many elderly may benefit from oral health promotion measures that involve the
      Atraumatic Restorative Treatment (ART) approach. The purpose of this study will
      be to evaluate, over 3 years of follow-up, the clinical behavior of atraumatic
      restorations placed in elderly patients. The study will comprise a structured
      interview, intraoral clinical examination, oral hygiene instructions and the
      atraumatic restorative treatment. Intraoral examination will be carried out as
      recommended by the World Health Organization (WHO). Small to medium size class I,
      II or V cavities without pulp involvement and spontaneous painful symptomatology
      will be selected to undergo the atraumatic restorative treatment. The
      restorations will be evaluated by direct observation at baseline and after 6, 12,
      24 and 36 months, using modified USPHS criteria. Two dentists with training and
      expertise in the ART approach, but who will not participate in the ART
      procedures, will evaluate the restorations.

PMID- 19089085
TI  - Atraumatic Restorative Treatment (ART): factors affecting success.
AB  - The success of tooth restorations rendered according to principles of the
      Atraumatic Restorative Treatment (ART) approach is dependant on various clinical
      factors. The most common failures, due to these factors, are partial material
      loss; complete material loss; caries related to restoration margin and material
      wear > 0.5mm. The main reason for clinical ART failures are related to operator
      skills and performance. The prevention and management of ART failures includes
      emphasis on correct clinical indication and the repair of failed restorations. A
      new caries classification may provide guidance for clinical indication. The
      classification combines site and size of a lesion, which is reflected in a dual
      coding system. In addition, ART training and diligence during ART application are
      important for clinical success.

PMID- 19089090
TI  - Editorial.

PMID- 19089091
TI  - Factors inhibiting the implementation of the Atraumatic Restorative Treatment
      approach in public oral health services in Gauteng Province, South Africa.
AB  - OBJECTIVE: To investigate potential barriers to the utilisation of the ART
      approach in a South African public oral health service. METHOD: 7 barriers were
      identified: patient load/work load, operator opinion, patient opinion, service
      management, material supply, clinical ART skill, chair-side assistance. Operators
      were asked to answer a questionnaire one year after completing the ART training.
      Responses ranged from 1 = no barrier to 5 = highest barrier. Treatment data per
      operator were collected during 1 year after training, for both dentitions,
      including: number of extracted teeth, placed traditional restorations, ART
      restorations. The restoration/extraction (REX) ratio and the proportion of ART
      restorations (ART%) of the total number of restorations were calculated and
      correlated with the barrier variables. Pearson correlation, ANOVA and 2-tailed t
      tests were used in the statistical analyses. RESULTS: Patient load/work load
      (mean = 2.80: SE = 0.16) was the strongest barrier (p<0.001) and clinical ART
      skill was the weakest barrier (p<0.001). A significant correlation between
      material supply and mean REX score was observed in both dentitions. In primary
      teeth, the ART% correlated significantly with clinical ART skill (r= -0.63;
      p<0.01). In permanent teeth, statistically significant correlations were observed
      between ART% and patient load/work load (r = -0.54; p<0.05), patient opinion (r =
      -0.76; p<0.01), operator opinion (r = -0.53; p<0.05), chair-side assistance (r = 
      0.57; p<0.05), oral health service management (r = -0.46; p<0.05). CONCLUSIONS: 1
      year after ART training completion high patient load/work load, followed by
      insufficient provision of materials/instruments, were the two most inhibiting
      barriers to the use of ART in the public oral health services. Dentists'
      perceptions of low clinical skill levels in performing ART confidently inhibited
      the use of ART in primary teeth in children.

PMID- 19089092
TI  - Assessment of the prevalence index on signs of combination syndrome in patients
      treated at Bauru School of Dentistry, University of Sao Paulo.
AB  - A group of destructive changes occurring in jaws in patients with maxillary
      complete dentures and mandibular removable partial dentures (bilaterally) has
      been described in the literature as the combination syndrome. However, this
      condition is not clinically observed in all patients. The aim of this study was
      to establish the prevalence index on signs of combination syndrome and to verify
      whether these changes also occurred in patients rehabilitated with a mandibular
      removable partial denture (unilaterally). Sample was composed of 44 patients,
      completely edentulous in the maxilla. Thirty-two patients had a Kennedy Class I
      removable partial denture and 12 a Kennedy Class II. Three major alterations were
      observed in 20.5% of the studied population. Nevertheless, these changes were
      present only in 25% of patients with Kennedy Class I removable partial denture.
      Based on the findings of this study, it can be concluded that patients with
      Kennedy Class II removable partial denture do not have similar signs that lead to
      the combination syndrome's condition.

PMID- 19089093
TI  - Digitizing radiographic films: a simple way to evaluate indirect digital images.
AB  - OBJECTIVES: This study applied a simple method to evaluate the performance of
      three digital devices (two scanners and one digital camera) using the
      reproducibility of pixel values attributed to the same radiographic image.
      METHODS: Using the same capture parameters, a radiographic image was repeatedly
      digitized in order to determine the variability of pixel values given to the
      image throughout the digitization process. One coefficient value was obtained and
      was called pixel value reproducibility. RESULTS: A significant difference in
      pixel values was observed among the three devices for the digitized images
      (ANOVA, p<0.00001). There was significant pixel value variability at the same
      digitization conditions for one scanner and the digital camera. CONCLUSIONS:
      Digital devices may assign pixel values differently in consecutive digitization
      depending on the optical density of the radiographic image and the equipment. The
      pixel value reproducibility was not satisfactory as tested for two devices. It is
      maybe advisable knowing the digitization variations regarding pixel values
      whenever using digital radiography images in longitudinal clinical examinations.

PMID- 19089094
TI  - Effect of thermocycling on the tensile and shear bond strengths of three soft
      liners to a denture base resin.
AB  - STATEMENT OF PROBLEM: In clinical practice, loss of adhesion between the silicone
      based denture liner and the denture base resin is always an undesirable event
      that might cause loss of material softness, water sorption, bacterial
      colonization and functional failure of the prosthesis. PURPOSE: This study
      evaluated the effect of thermocycling on tensile and shear bond strengths of
      three soft liner materials to a denture base acrylic resin. MATERIAL AND METHODS:
      Three resilient liners (Mucopren-Soft, Mollosil-Plus and Dentusil) and a heat
      polymerized acrylic resin (QC-20) were processed according to manufacturers'
      directions. Sixty specimens (14 x 14 mm cross-sectional area) per bond strength
      test (20 for each liner) were fabricated and either stored in water at 37 degrees
      C for 24 hours (control groups; n=10) or thermocycled 3,000 times in water
      between 5 degrees C and 55 degrees C (test groups; n=10). The specimens were
      tested in tensile and shear strength in a universal testing machine until
      fracture. Bond strength means were compared between water-stored and thermocycled
      groups for each material, as well as among materials for each treatment (water
      storage or thermocycling). Failure mode (adhesive, cohesive and mixed) after
      debonding was assessed. Data were analyzed statistically by paired Student's t
      test and ANOVA at 5% significance level. RESULTS: The water-stored groups had
      statistically significant higher bond strengths than the thermocycled groups
      (p<0.05). Without thermocycling, Mucopren-Soft (2.83 +/- 0.48 MPa) had higher
      bond strength than Mollosil-Plus (1.04 +/- 0.26 MPa) and Dentusil (1.14 +/- 0.51
      MPa). After thermocycling, Mucopren-Soft (1.63 +/- 0.48 MPa) had the highest bond
      strength (p<0.05). CONCLUSION: The bond strength of the three soft denture liners
      tested in this study changed with their chemical composition and all of them
      exhibited higher bond strengths than those usually reported as clinically
      acceptable. CLINICAL IMPLICATIONS: All soft lining materials tested in this study
      showed a significant decrease in the bond strength to an acrylic denture base
      resin after thermocycling. In spite of thermocycling, though, the silicone-based
      liners had satisfactory bond strengths for clinical application.

PMID- 19089095
TI  - Oral myofunctional and electromyographic evaluation of the anterior suprahyoid
      muscles and tongue thrust in patients with Class II/1 malocclusion submitted to
      first premolar extraction.
AB  - OBJECTIVE: The aim of this study was to assess the existence of myofunctional
      alterations before and after first premolar extraction in Class II/1 malocclusion
      patients that could endanger the long-term dental arch stability. MATERIAL AND
      METHODS: The study was performed by means of morphological, functional and
      electromyographic analyses in 17 Class II/1 malocclusion patients (group T) and
      17 Class I malocclusion patients (group C), both groups with 12-30-year age range
      (mean age: 20.93 +/- 4.94 years). RESULTS: Data analyzed statistically by
      Student's t-test showed a significant decrease in the maxillary and mandibular
      dental arch perimeters after orthodontic treatment (p<0.05). The Kruskal-Wallis
      test analyzed data from tongue posture at rest and during swallowing, not showing
      significant differences after treatment (groups Tb and Ta) (p>0.05). However,
      group T differed significantly from group C (p<0.05). The electromyographic data
      showed that the anterior right and left suprahyoid muscles acted synergistically
      in both groups, while having a lower myoelectric activity in group T during
      swallowing. CONCLUSIONS: Myofunctional alterations observed after the orthodontic
      treatment in Class II/1 malocclusion seemed to jeopardize the long-term
      orthodontic stability, making recurrence possible. Further research should be
      conducted to compare electromyographic data before and after orthodontic
      treatment in order to corroborate the results of the present investigation.

PMID- 19089097
TI  - Evaluation of ocular prosthesis biofilm and anophthalmic cavity contamination
      after use of three cleansing solutions.
AB  - In addition to an initial socket discomfort, ocular prosthesis (OP) installation
      may allow the adherence of fungi and/or bacteria due to the superficial
      characteristics of the prosthesis' material, use of inadequate cleansing
      solutions and methods, or because the void located between the internal portion
      of the prosthesis and the anophthalmic cavity (AC) mucosa. OBJECTIVE: The aim of
      this study was to evaluate OP biofilm formation and the level of contamination of
      the internal portion of the OP and the AC in 24 patients. MATERIAL AND METHODS:
      Material was collected from the AC at the beginning of the study and 15 days
      after cleansing of the OP with 3 cleansing solutions: a neutral liquid soap, a
      multiuse solution for contact lens (Complete) and 0.12% chlorhexidine
      (Periogard). The collected materials were sowed in Petri dishes containing
      selective media for aerobic and facultative microorganisms, specifically
      staphylococci (Hipersalt agar with egg yolk), aerobic microorganisms (Brain Heart
      Infusion Blood Agar), streptococci (Mitis salivarius Agar), gram-negative bacilli
      (MacConkey Agar) and yeasts (Chromagar Candida), incubated at 35 degrees C or 37
      degrees C and the number of colony forming units were counted. Data were analyzed
      statistically by ANOVA, Friedman's test and Spearman's correlation. RESULTS:
      Aerobic microorganisms, gram-negative bacilli and S. aureus were found in the OP
      biofilm and in the AC. There was statistically significant difference (p<0.05)
      between the number of microorganisms before and after the use of the cleansing
      solutions. CONCLUSION: There was positive correlation with respect to the
      microorganisms present in the OP biofilm and AC for the 4 proposed treatments,
      indicating that the decrease of OP contamination leads to AC contamination as
      well.

PMID- 19089096
TI  - Comparison of the fracture resistance of endodontically treated teeth restored
      with prefabricated posts and composite resin cores with different post lengths.
AB  - OBJECTIVE: This study evaluated the fracture strengths of endodontically treated
      teeth restored with prefabricated posts with different post lengths. MATERIAL AND
      METHODS: Thirty freshly extracted canines were endodontically treated. They were
      randomly divided into groups of 10 teeth and prepared according to 3 experimental
      protocols, as follows; Group 1/3 PP: teeth restored with prefabricated post and
      composite resin core (Z250) with post length of 5.0mm; Group 1/2 PP and Group 2/3
      PP: teeth restored with prefabricated post and composite resin core (Z250) with
      different combinations of post length of 7.5mm and 10mm, respectively. All teeth
      were restored with full metal crowns. The fracture resistance (N) was measured in
      a universal testing machine (crosshead speed 0.5mm/min) at 45 degrees to the
      tooth long axis until failure. Data were analyzed by one-way analysis of variance
      (alpha=.05). RESULTS: The one-way analysis of variance demonstrated no
      significant difference among the different post lengths (P>.05) (Groups 1/3 PP =
      405.4 N, 1/2 PP = 395.6 N, 2/3 PP = 393.8 N). Failures occurred mainly due to
      core fracture. CONCLUSIONS: The results of this study showed that an increased
      post length in teeth restored with prefabricated posts did not significantly
      increase the fracture resistance of endodontically treated teeth.

PMID- 19089098
TI  - Efficacy of three denture brushes on biofilm removal from complete dentures.
AB  - The aim of this study was to compare the efficacy of three denture brushes
      (Bitufo-B; Medic Denture-MD; Colgate-C) on biofilm removal from upper and lower
      dentures using a specific dentifrice (Corega Brite). The correlation between
      biofilm levels on the internal and external surfaces of the upper and lower
      dentures was also evaluated. A microbiological assay was performed to assess the
      growth of colony-formed units (cfu) of Candida yeasts on denture surface. Thirty
      three patients were enrolled in a 10-week trial divided in two stages: 1
      (control) - three daily water rinses within 1 week; 2 - three daily brushings
      within 3 weeks per tested brush. Internal (tissue) and external (right buccal
      flange) surfaces of the complete dentures were disclosed (neutral red 1%) and
      photographed. Total denture areas and disclosed biofilm areas were measured using
      Image Tool 3.00 software for biofilm quantification. Dentures were boxed with #7
      wax and culture medium (CHROMagar Candida) was poured to reproduce the internal
      surface. Statistical analysis by Friedman's test showed significant difference
      (p<0.01) between control and brushing stages. No difference was found among the
      brushes with respect to their efficacy on biofilm removal (p>0.01). Analysis by
      the Correlation test showed higher r values (B=0.78; MD=0.8341, C=0.7362) for the
      lower dentures comparing the surfaces (internal and external) and higher r values
      (B=0.7861, MD=0.7955, C=0.8298) for the external surface comparing the dentures
      (upper and lower). The results of the microbiological showed no significant
      difference (p>0.01) between the brushes with respect to the frequency of the
      species of yeasts (chi-square test). In conclusion, all denture brushes evaluated
      in this study were effective in the removal of biofilm. There was better
      correlation of biofilm levels between the surfaces for the lower dentures, and
      between the dentures for the external surface. There was no significant
      difference among the brushes regarding the frequency of yeasts.

PMID- 19089099
TI  - Influence of the final temperature of investment healting on the tensile strength
      and Vickers hardness of CP Ti and Ti-6Al-4V alloy.
AB  - The aim of the work was to evaluate the influence of the temperature of
      investment healting on the tensile strength and Vickers hardness of CP Ti and Ti
      6Al-4V alloy casting. Were obtained for the tensile strength test dumbbell rods
      that were invested in the Rematitan Plus investment and casting in the Discovery
      machine cast. Thirty specimens were obtained, fifteen to the CP Titanium and
      fifteen to the Ti-6Al-4V alloy, five samples to each an of the three temperatures
      of investment: 430 degrees C (control group), 480 degrees C and 530 degrees C.
      The tensile test was measured by means of a universal testing machine, MTS model
      810, at a strain of 1.0 mm/min. After the tensile strength test the specimens
      were sectioned, embedded and polished to hardness measurements, using a Vickers
      tester, Micromet 2100. The means values to tensile tests to the temperatures 430
      degrees C, 480 and 530: CP Ti (486.1 - 501.16 - 498.14 -mean 495.30 MPa) and Ti
      6Al-4V alloy (961.33 - 958.26 - 1005.80 - mean 975.13 MPa) while for the Vickers
      hardness the values were (198.06, 197.85, 202.58 - mean 199.50) and (352.95,
      339.36, 344.76 - mean 345.69), respectively. The values were submitted to
      Analysis of Variance (ANOVA) and Tukey Test that indicate differences significant
      only between the materials, but not between the temperature, for both the
      materials. It was concluded that increase of the temperature of investment its
      not chance the tensile strength and the Vickers hardness of the CP Titanium and
      Ti-6Al-4V alloy.

PMID- 19089100
TI  - Evaluation of internal adaptation of Class V resin composite restorations using
      three techniques of polymerization.
AB  - OBJECTIVE: The purpose of this in vitro study was to evaluate the internal
      adaptation of Class V composite restorations to the cavity walls using three
      different techniques of polymerization. METHODS: Standard cavities were prepared
      on the buccal and lingual surfaces of 24 extracted human third molars with
      margins located above and below the cementoenamel junction. Restorations were
      placed in one increment using two restorative systems: 3M Filtek A110/ Single
      Bond (M) and 3M Filtek Z250/ Single Bond (H) in the same tooth, randomly in the
      buccal and lingual surfaces. Resin composites were polymerized using three
      techniques: Group 1 - Conventional (60 s - 600 mW/cm(2)); Group 2 - Soft-start
      (20 s - 200 mW/cm(2) , 40 s - 600 mW/cm(2)); Group 3 - Pulse Activation (3 s -
      200 mW/cm(2), 3-min hiatus, 57 s - 600 mW/cm(2)). Buccolingual sections were
      polished, impressions taken and replicated. Specimens were assessed under
      scanning electron microscopy up to X1000 magnification. Scores were given for
      presence or absence of gaps (0 - no gap; 1 - gap in one wall; 2 - gap in two
      walls; 3 - gap in three walls). RESULTS: The mean scores of the groups were (+/
      SD) were: G1M-3.0 (+/- 0.0); G2M-2.43 (+/- 0.8); G3M- 1.71 (+/- 0.9); G1H- 2.14
      (+/- 1.2); G2H- 2.00 (+/- 0.8); G3H- 1.67 (+/- 1.1). Data were analyzed using
      Kruskal-Wallis and Dunnet's tests. No statistically significant difference
      (p>0.05) was found among groups. Gaps were observed in all groups. CONCLUSIONS:
      The photocuring technique and the type of resin composite had no influence on the
      internal adaptation of the material to the cavity walls. A positive effect was
      observed when the slow polymerization techniques were used.

PMID- 19089101
TI  - Mastication and swallowing: influence of fluid addition to foods.
AB  - INTRODUCTION: The production of sufficient saliva is indispensable for good
      chewing. Recent research has demonstrated that salivary flow rate has little
      influence on the swallowing threshold. OBJECTIVES: The hypothesis examined in the
      present study was that adding fluids to foods will influence chewing physiology.
      MATERIALS AND METHODS: Twenty subjects chewed on melba toast, cake, carrot,
      peanut and Gouda cheese. They also chewed on these foods after addition of
      different volumes of water or alpha-amylase solution. Jaw muscle activity, number
      of chewing cycles until swallowing and chewing cycle duration were measured.
      Repeated measures analysis of variance was applied to test the null hypothesis
      that there would be no statistically significant difference among the results
      obtained for the various food types and fluids. Subsequently, contrasts were
      determined to study the levels of intra-subjects factors (food type and fluid
      volume). Linear regression was used to determine the changes in muscle activity
      and cycle duration as a function of the chewing cycles. RESULTS: Fluid addition
      significantly decreased muscle activity and swallowing threshold for melba, cake
      and peanut (p<0.05). The effect of alpha-amylase in the solutions was similar to
      that of water (p>0.05). Doubling the volume of tap water had a greater effect.
      CONCLUSIONS: Fluid addition facilitated chewing of dry foods (melba, cake), but
      did not influence the chewing of fatty (cheese) and wet products (carrot). This
      study is relevant to improve patients' life quality and the management of chewing
      and feeding disorders caused by hyposalivation.

PMID- 19089102
TI  - Effect of iron supplementation on the erosive potential of carbonated or
      decarbonated beverage.
AB  - This study evaluated, in vitro, the effect of iron (previously exposed with
      enamel powder or added directly to the beverage) on the erosive potential of
      carbonated or decarbonated beverage. Four sets of experiments were done. For
      groups E1 and E3, a solution containing 30 mmol/L FeSO4 was added to bovine
      enamel powder (particles between 75-106 mm) before exposure to the carbonated or
      decarbonated beverage (Sprite Zero(R)), respectively. For groups E2 and E4, 15
      mmol/L FeSO4 was added directly to the carbonated or decarbonated beverage,
      respectively. Control groups were included for comparison. In controls C1 and C3,
      the experiments E1 and E3 were repeated, but the iron solution was replaced by
      deionized water. For controls C2 and C4, the carbonated and decarbonated
      beverage, respectively, was used, without addition of iron. After addition of the
      beverage to the powdered enamel (40 mg enamel powder/400 mL of final volume), the
      sample was vortexed for 30 s and immediately centrifuged for 30 s (11,000 rpm).
      The supernatant was removed after 1 min 40 s. This procedure was repeated in
      quintuplicate and the phosphate released was analyzed spectrophotometrically. The
      results were analyzed by Student's t-test (p<0.05). E2 presented the best results
      with a significant inhibition (around 36%) of phosphate released. For E3 and E4 a
      non-significant inhibition (around 4 and 12%, respectively), was observed. For E1
      an increase in phosphate loss was detected. Thus, the protective effect of iron
      seems to be better when this ion is directly added to the carbonated beverage.

PMID- 19089103
TI  - In vitro evaluation of root canal preparation using oscillatory and rotary
      systems in flattened root canals.
AB  - OBJECTIVE: The aim of this study was to evaluate the biomechanical preparation of
      flattened root canals using the following systems: Endo-Eze AET stainless steel
      oscillatory instruments (Ultradent) and RaCe rotary NiTi instruments (FKG
      Dentaire). MATERIAL AND METHODS: Twenty extracted human mandibular incisors were
      randomly assigned to two groups: Group 1 - Instrumentation with oscillatory Endo
      Eze AET files (oscillatory technique); Group 2 - Instrumentation with rotary NiTi
      RaCe files (rotary technique). The teeth were decoronated, had their apices and
      coronal openings sealed with sticky wax and were embedded in crystal-clear
      orthophtalic polyester resin. The roots were sectioned transversally with diamond
      discs at 10 mm (middle third) and 5 mm (apical third) from the apex and the
      segments were reassembled for instrumentation. The sections were photographed
      before and after root canal instrumentation and evaluated with respect to whether
      the original root canal shape was modified by instrumentation. To evaluate the
      differences in the root canal shape before and after biomechanical preparation,
      scores were given regarding the instruments touch on the intracanal walls.
      RESULTS: In middle third of the root canals instrumented with the rotary system,
      there was a change in the original canal anatomy (p<0.05), with formation of a
      protuberance in the mesiodistal direction. This protuberance did not occur when
      the oscillatory instrumentation was used. The oscillatory system had better
      results in the middle and apical thirds as evaluated by Dunn's multiple
      comparison test (p>0.05). CONCLUSION: Under the tested conditions, Endo-Eze
      oscillatory system yielded the instrumentation of all flattened root canal walls,
      maintaining the canal original shape throughout the biomechanical preparation,
      and was more effective than RaCe rotary system.

PMID- 19089104
TI  - Determination of tangential and normal components of oral forces.
AB  - Oral forces applied to human teeth during biting and mastication are normally
      described in the literature only in terms of their axial components. The purpose
      of this study was to fully determine the spatial characteristics of the oral
      resultant force - its normal and tangential components - for a given individual.
      A load cell was especially manufactured to measure oral force and was temporarily
      implanted as a prosthetic device in the dental arch of a volunteer, replacing his
      missing upper first molar. The mastication and occlusion tests were carried out
      in such a way the cell should withstand the loads applied to the molar, and its
      state of strain was recorded by strain gauges attached to it. Based on the
      results of these tests and using balance equations, normal and tangential
      components of the resultant oral force were determined. For direct occlusion,
      without interposition any obstacle between cusps, a peak normal force of 135 N
      was recorded simultaneously to a tangential force of 44 N. For mastication of
      biscuits, a peak normal force of 133 N and a tangential force of 39 N were
      obtained.

PMID- 19089105
TI  - Examination of temporomandibular disorders in the orthodontic patient: a clinical
      guide.
AB  - The possible association between orthodontic treatment and temporomandibular
      disorders (TMD) is a topic of great interest in the current literature. The true
      role of orthodontic therapy on the etiology of TMD, however, is still uncertain.
      From the clinical prospective, a thorough examination of the stomatognathic
      system is always necessary in order to detect possible TMD signs and symptoms
      prior to the beginning of the orthodontic therapy. Caution should be exercised
      when planning, performing and finalizing orthodontics, especially in patients who
      with history of signs and symptoms of TMD. The clinician must always eliminate
      patient's pain and dysfunction before initiating any type of orthodontic
      mechanics. Muscle incoordination, unstable disc-condyle relationship and bone
      alterations are usual TMD conditions that can interfere with the presenting
      occlusal relationship. This article reviews these aspects and presents a detailed
      clinical guide for the examination of the orthodontic patient, considering
      aspects related to facial pain and dysfunction.

PMID- 19089106
TI  - Current pattern of antibiotics prescription to prevent surgical site infection
      after lower third molar removal.

PMID- 19089107
TI  - Sugar-free chewing gum and dental caries: a systematic review.
AB  - OBJECTIVE: To appraise existing evidence for a therapeutic / anti-cariogenic
      effect of sugar-free chewing gum for patients. METHOD: 9 English and 2 Portuguese
      databases were searched using English and Portuguese keywords. Relevant articles
      in English, German, Portuguese and Spanish were included for review. Trials were
      excluded on lack of randomisation, control group, blinding and baseline data,
      drop out rate > 33%, no statistical adjustment of baseline differences and no
      assessment of clinically important outcomes. Reviews were excluded on lack of
      information, article selection criteria, search strategy followed, search
      keywords, searched databases or lack of study-by-study critique tables. In cases
      of multiple reports from the same study, the report covering the longest period
      was included. Two reviewers independently reviewed and assessed the quality of
      accepted articles. RESULTS: Thirty-nine articles were included for review. Thirty
      were excluded and 9 accepted. Of the 9 accepted, 2 trials of reasonable and good
      evidence value did not demonstrate any anti-cariogenic effect of sugar-free
      chewing gum. However, 7 articles, with 1 of strong, and 6 of good evidence value,
      demonstrated anti-cariogenic effects of chewing Sorbitol, Xylitol or
      Sorbitol/Xylitol gum. This effect can be ascribed to saliva stimulation through
      the chewing process, particularly when gum is used immediately after meals; the
      lack of sucrose and the inability of bacteria to metabolize polyols into acids.
      CONCLUSION: The evidence suggests that sugar-free chewing gum has a caries
      reducing effect. Further well-designed randomised trials are needed to confirm
      these findings.

PMID- 19089108
TI  - A quantitative analysis of rotary, ultrasonic and manual techniques to treat
      proximally flattened root canals.
AB  - OBJECTIVE: The efficiency of rotary, manual and ultrasonic root canal
      instrumentation techniques was investigated in proximally flattened root canals.
      MATERIAL AND METHODS: Forty human mandibular left and right central incisors,
      lateral incisors and premolars were used. The pulp tissue was removed and the
      root canals were filled with red die. Teeth were instrumented using three
      techniques: (i) K3 and ProTaper rotary systems; (ii) ultrasonic crown-down
      technique; and (iii) progressive manual technique. Roots were bisected
      longitudinally in a buccolingual direction. The instrumented canal walls were
      digitally captured and the images obtained were analyzed using the Sigma Scan
      software. Canal walls were evaluated for total canal wall area versus non
      instrumented area on which dye remained. RESULTS: No statistically significant
      difference was found between the instrumentation techniques studied (p<0.05).
      CONCLUSION: The findings of this study showed that no instrumentation technique
      was 100% efficient to remove the dye.

PMID- 19089109
TI  - Effect of a bonding resin layer associated with a self-etching adhesive system on
      the bond strength of indirect restorations.
AB  - The aim of this study was to evaluate the influence of a low-viscosity bonding
      resin applied over a self-etching adhesive system on the microtensile bond
      strength (microTBS) of indirect restorations. Comparisons were made using One Up
      Bond F (OB) self-etching adhesive system, Single Bond (SB) one-bottle adhesive
      system and Scotchbond Multi Purpose Plus (SMP) bonding component. Thirty bovine
      incisors were extracted and decoronated at the cementoenamel junction. The labial
      surfaces were ground so that superficial dentin and deep dentin were exposed. The
      specimens were randomized to three groups (n=10): G1- OB; G2- OB + SMP; G3- SB.
      In G2, a layer of the SMP bonding was applied over the OB adhesive system.
      Indirect composite restorations were bonded using dual-cure cement under 500 g
      load for 5 min. The specimens were serially sectioned with a bonding area of +/-
      1.0 mm(2) in 3 regions: enamel (E), superficial dentin (SD) and deep dentin (DD).
      The sticks were fixed with cyanoacrylate adhesive and submitted to microTBS test
      at a crosshead speed of 0.5 mm/min in a mechanical testing machine (EMIC DL
      2000). The fractured specimens were examined under scanning electron microscopy
      to determine the failure mode. Data were analyzed by one-way ANOVA followed by
      Tukey's test (p<0.05). microTBS means (in MPa) were: G1/E: 15.5 +/- 3.5b; G1/SD:
      22.7 +/- 7.6a; G1/DD: 19.4 +/- 9.4a; G2/E: 15.9 +/- 5.8b; G2/SD: 19.9 +/- 6.9a;
      G2/DD: 15.3 +/- 4.9a; G3/E: 23.2 +/- 7.3a; G3/SD: 20.4 +/- 8.2a; G3/DD: 19.1 +/-
      8.7a. The results showed that the use of a low viscosity bonding resin did not
      affect the microTBS means when associated with a self-etching adhesive system.
      The self-etching adhesive system was significantly more efficient in dentin than
      in enamel, while the one-bottle system was significantly more efficient in enamel
      when compared to the self-etching adhesive system.

PMID- 19089110
TI  - Dental maturity as an indicator of chronological age: radiographic assessment of
      dental age in a Brazilian population.
AB  - OBJECTIVE: The purpose of this investigation was to evaluate the applicability of
      the methods proposed by Nolla and by Nicodemo and colleagues for assessing dental
      age and its correlation to chronological age. METHODS: Panoramic radiographs of
      360 patients from the city of Fortaleza (CE, Brazil) aged 7-15 years were used to
      assess the associations between dental and chronological age. Data were submitted
      to statistical analysis using the BioEstat 2.0 (2000) software. Student-Neuman
      Keuls test was performed and Pearson's correlation coefficients were calculated
      at 5% significance level. RESULTS: When the Nolla method was applied, the mean
      difference between true and estimated age for males and females was
      underestimated. The use of the method proposed by Nicodemo and colleagues also
      resulted in underestimation, although it was more evident in male subjects. The
      correlation coefficients between chronological age and estimated dental age were
      high, with mean values ranging between 0.87 and 0.91 for males and between 0.84
      and 0.93 for females. CONCLUSION: Although both methods proved to be reliable in
      estimating age, the use of correction factors is recommended.

PMID- 19089111
TI  - Effect of light curing modes and ethanol immersion media on the susceptibility of
      a microhybrid composite resin to staining.
AB  - The aim of this in vitro study was to evaluate the susceptibility of a hybrid
      composite resin (Filtek Z250 - 3M ESPE) to staining, when light cured in four
      different modes and immersed in two different media. Composite resin specimens
      were randomly prepared and polymerized according to the experimental groups
      (conventional -50 mW/cm(2) / 30 seconds; soft start -300 mW/cm(2) / 10 seconds +
      550 mW/cm(2) / 20 seconds; high intensity -1060 mW/cm(2)--10 seconds; pulse delay
      -550 mW/cm(2)--1 seconds + 60 seconds of waiting time + 550 mW/cm(2)--20 seconds)
      and immersed in one of two media (distilled water or absolute ethanol) for 24 h.
      Next, the specimens were immersed in a 2% methylene blue solution for 12 hours.
      Afterwards, the specimens were washed and prepared for the spectrophotometric
      analysis. For statistical analysis, two-way ANOVA (4X2) and Tukey's test were
      performed on the data at 0.05 confidence level. Soft start showed the least
      staining, and was statistically different from the high intensity and pulse delay
      light curing modes (p<0.05). Conventional light curing unit did not show
      statistically significant differences from any other groups (p>0.05). There were
      no significant differences between the two immersion media (p>0.05). The soft
      start polymerization mode showed lower susceptibility of the composite resin to
      staining than high intensity and pulse delay, irrespective of the immersion
      medium.

PMID- 19089112
TI  - Assessment of temporomandibular disorder and occlusion in treated class III
      malocclusion patients.
AB  - OBJECTIVE: The aims of this study were to compare the prevalence of
      temporomandibular disorders (TMD) in individuals submitted to either orthodontic
      or ortho-surgical Class III malocclusion treatment and to assess the influence of
      occlusal aspects on TMD severity. MATERIAL AND METHODS: The sample consisted of
      50 individuals divided into two groups, according to the type of treatment
      (orthodontic or orthodontic with orthognathic surgery). The presence of signs and
      symptoms of TMD was evaluated by an anamnestic questionnaire and a clinical
      examination, including TMJ and muscle palpation, active mandibular range of
      motion, joint noises and occlusal examination. RESULTS: Based on the anamnestic
      questionnaire, 48% had no TMD, 42% had mild TMD and 10% had moderate TMD. The
      presence and severity of TMD did not show any relationship with the type of
      orthodontic treatment (p>0.05). The chi-square test showed a positive association
      (p<0.05) between TMD and non-working side occlusal interferences. CONCLUSION:
      Based on the methodology used and the results obtained, it may be concluded that
      Class III orthodontic treatment was not associated with the presence of TMD signs
      and symptoms and the non-working side contacts can be occlusal factors of risk.
      There was no significant difference in TMD prevalence between the studied groups
      (orthodontically treated patients and patients treated with orthodontics followed
      by orthognathic surgery).

PMID- 19089113
TI  - Relationship between cranial and mandibular growth and the stages of maturation
      of the cervical vertebrae.
AB  - Quantification of the expectation of craniofacial growth during the pubertal
      growth spurt (PGS) is helpful in orthodontic diagnosis and treatment planning.
      Thus, this study investigated whether the stages of the vertebral maturation
      index (VMI) would be valid for estimating cranial and mandibular growth during
      the initial stages of PGS, testing the null hypothesis that these structures do
      not demonstrate differential growth dependent on the maturation stage. A study
      population of 45 patients of both genders with 2 lateral cephalometric
      radiographs, taken at a 12-month interval, was selected from files. All patients
      should not have been previously submitted to orthodontic treatment and should be
      before or during the peak stage of PGS. The S-N and Co-Gn cephalometric
      measurements were traced on both radiographs of each patient, by computed
      cephalometric tracings, for evaluation of skull and mandible, respectively. The
      growth of these structures was established by the difference between the
      measurements obtained on both tracings. The VMI stage was also estimated on the
      radiographs, determining the position of patients on the PGS curve at two
      periods, baseline and after 12 months. Cephalometric tracings and VMI estimates
      were performed by two calibrated examiners. Descriptive statistics revealed that
      both cephalometric measurements increased during the study period, especially Co
      Gn, which demonstrated (ANOVA and Tukey's test; 5% significance level), a
      statistically significant peak of development (p = 0.001), when the patient was
      in the VMI stage representing the PGS peak. It was concluded that the VMI stages
      were valid for the analysis of cranial growth and especially of mandibular growth
      at the initial stages of PGS, thus rejecting the null hypothesis.

PMID- 19089114
TI  - Desensitizing bioactive agents improves bond strength of indirect resin-cemented
      restorations: preliminary results.
AB  - OBJECTIVE: The aim of this study was to assess the bond strength of indirect
      composite restorations cemented with a resin-based cement associated with etch
      and-rinse and self-etching primer adhesive systems to dentin treated or not with
      a bioactive material. MATERIALS AND METHOD: Twenty bovine incisor crowns had the
      buccal enamel removed and the dentin ground flat. The teeth were assigned to 4
      groups (n=5): Group I: acid etching + Prime & Bond NT (Dentsply); Group II:
      application of a bioactive glass (Biosilicato) + acid etching + Prime & Bond NT;
      Group III: One-up Bond F (J Morita); Group IV: Biosilicato + One-up Bond F.
      Indirect composite resin (Artglass, Kulzer) cylinders (6 x 10 mm) were fabricated
      and cemented to the teeth with a dual-cure resin-based cement (Enforce,
      Dentsply). After cementation, the specimens were stored in artificial saliva at
      37 degrees C for 30 days and thereafter tested in tensile strength in a universal
      testing machine (EMIC) with 50 kgf load cell at a crosshead speed of 1 mm/min.
      Failure modes were assessed under scanning electron microscopy. Data were
      analyzed statistically by ANOVA and Tukey's test (95% level of confidence).
      RESULTS: Groups I, II and III had statistically similar results (p>0.05). Group
      IV had statistically significant higher bond strength means (p<0.05) than the
      other groups. The analysis of the debonded surfaces showed a predominance of
      adhesive failure mode for Group III and mixed failure mode for the other groups.
      CONCLUSION: The use of desensitizing agent did not affect negatively the bonding
      of the indirect composite restorations to dentin, independently of the tested
      adhesive systems.

PMID- 19089115
TI  - Shear bond strength of orthodontic brackets to enamel under different surface
      treatment conditions.
AB  - The purpose of the present study was to evaluate the shear bond strength to
      enamel and the adhesive remnant index (ARI) of both metallic and polycarbonate
      brackets bonded under different conditions. Ninety bovine permanent mandibular
      incisors were embedded in acrylic resin using PVC rings as molds and assigned to
      6 groups (n=15). In Groups 1 (control) and 3, metallic and polycarbonate
      orthodontic brackets were, respectively, bonded to the enamel surfaces using
      Transbond XT composite according to the manufacturer's recommendations. In Groups
      2 and 4, both types of brackets were bonded to enamel with Transbond XT
      composite, but XT primer was replaced by the OrthoPrimer agent. In Groups 5 and
      6, the polycarbonate bracket bases were sandblasted with 50-microm aluminum-oxide
      particle stream and bonded to the enamel surfaces prepared under the same
      conditions described in Groups 3 and 4, respectively. After bonding, the
      specimens were stored in distilled water at 37 degrees C for 24 hours and then
      submitted to shear bond strength test at a crosshead speed of 0.5 mm/min. The
      results (MPa) showed no statistically significant difference between Groups 4 and
      6 (p>0.05). Likewise, no statistically significant differences (p>0.05) were
      found among Groups 1, 2, and 5, although their results were significantly lower
      than those of Groups 4 and 6 (p<0.05). Group 3 had statistically significant
      lower bond strength than Groups 2, 4, and 6, but no statistically significant
      differences were found on comparison to Groups 1 and 5. A larger number of
      fractures at the bracket/composite interface were evidenced by the ARI scores.
      OrthoPrimer bonding agent yielded higher bond strength in the groups using either
      conventional or sandblasted polycarbonate brackets, which was not observed in the
      groups using metallic brackets.

PMID- 19089116
TI  - Evaluation of the thermoplasticity of different gutta-percha cones and the TC
      system.
AB  - OBJECTIVE: The aim of this study was to evaluate the thermoplasticity of three
      commercial brands of gutta-percha (Tanari, Dentsply 0.06, and Roeko), and of the
      TC system. MATERIALS AND METHODS: Standardized specimens were fabricated from the
      materials to be evaluated. Specimens were placed in water at 70 degrees C for 60
      seconds. Following that, they were positioned between two glass slabs and each
      set was compressed by a 5 kg weight. Images of the specimens before and after
      compression were digitized and analyzed by the Image Tool software. The flow
      capacity of each material was confirmed by the difference between the initial and
      final areas of each sample. RESULTS: The resulting data were analyzed by ANOVA.
      The TC system presented the greatest thermoplasticity values (p<0.05). Among the
      gutta-percha cones, the Roeko brand showed higher thermoplasticity than the
      others (p<0.05). CONCLUSION: The gutta-percha from TC system present good
      thermoplasticity capacity.

PMID- 19089117
TI  - Computed tomography imaging strategies and perspectives in orbital fractures.
AB  - OBJECTIVE: The objective of this study was to demonstrate the sensitivity and
      specificity of multislice computed tomography (CT) for diagnosis of orbital
      fractures following different protocols, using an independent workstation.
      MATERIALS AND METHODS: CT images of 36 patients with maxillofacial fractures
      (symptomatic to orbit region) who were submitted to multislice CT scanning were
      analyzed, retrospectively. The images were interpreted based on 5 protocols,
      using an independent workstation: 1) axial (original images); 2) multiplanar
      reconstruction (MPR); 3) 3D images; 4) association of axial/MPR/3D images and 5)
      coronal images. The evaluated anatomical sites were divided according to the
      orbital walls: lateral (with or without zygomatic frontal process fracture);
      medial; superior (roof) and inferior (anterior, medial). The collected data were
      analyzed statistically using a validity test (Youden's J index; p<0.05). The
      clinical and/or surgical findings (medical records) were considered as the gold
      standard to corroborate the diagnosis of the anatomical localization of the
      orbital fracture. RESULTS: 3D-CT scanning presented sensitivity of 78.9%, which
      was not superior to that of MPR (84.0%), axial/MPR/3D (90.5%) and coronal images
      (86.1%). On the other hand, the diagnostic value of axial images was considered
      limited for orbital fractures region, with sensitivity of 44.2%. CONCLUSIONS:
      Except for the axial images, which presented a low sensitivity, all methods
      evaluated in this study showed high specificity and sensitivity for the diagnosis
      of orbital fractures according to the proposed methodology. This protocol can add
      valuable information to the diagnosis of fractures using the association of
      axial/MPR/3D with multislice CT.

PMID- 19089118
TI  - Prevalence of dental fluorosis in Bauru, Sao Paulo, Brazil.
AB  - OBJECTIVE: To evaluate the prevalence of dental fluorosis in scholars aging 12 to
      15 years old, residents in the city of Bauru, State of Sao Paulo, Brazil.
      METHODS: 1318 volunteers were enrolled in this study and examined in 18 public
      schools of the State of Sao Paulo. The examinations were performed in the
      schools' court by three dentists (with a Master's degree in Public Health), after
      toothbrushing supervised by another dentist. The teeth were dried with cotton
      pellets and examined under natural light by visual inspection, using an explorer
      as recommended by the WHO, a plane mirror and a tongue depressor. The Thylstrup
      Fejerskov (TF) index was used for rating fluorosis. Intra and inter-examiner
      reproducibility was calculated and data were submitted to descriptive analysis.
      RESULTS: Approximately 36% of the children presented dental fluorosis, of which
      28% was diagnosed as TF1 while the remaining received scores between TF2 and TF4.
      CONCLUSION: The prevalence of dental fluorosis in Bauru is within the expected
      range, based on previous studies. Although fluoride is an important resource for
      caries control, its use must be adequate to the needs of each specific
      population.

PMID- 19089119
TI  - Use of cervical vertebral dimensions for assessment of children growth.
AB  - OBJECTIVE: The purpose of this study was to investigate whether skeletal
      maturation using cephalometric radiographs could be used in a Brazilian
      population. MATERIAL AND METHODS: The study population was selected from the
      files of the Oral Radiological Clinic of the Dental School of Piracicaba, Brazil
      and consisted of 128 girls and 110 boys (7.0 to 15.9 years old) who had
      cephalometric and hand-wrist radiographs taken on the same day. Cervical
      vertebral bone age was evaluated using the method described by Mito and
      colleagues in 2002. Bone age was assessed by the Tanner-Whitehouse (TW3) method
      and was used as a gold standard to determine the reliability of cervical
      vertebral bone age. An analysis of variance and Tukey's post-hoc test were used
      to compare cervical vertebral bone age, bone age and chronological age at 5%
      significance level. RESULTS: The analysis of the Brazilian female children data
      showed that there was a statistically significant difference (p<0.05) between
      cervical vertebral bone age and chronological age and between bone age and
      chronological age. However no statistically significant difference (p>0.05) was
      found between cervical vertebral bone age and bone age. Differently, the analysis
      of the male children data revealed a statistically significant difference
      (p<0.05) between cervical vertebral bone age and bone age and between cervical
      vertebral bone age and chronological age (p<0.05). CONCLUSIONS: The findings of
      the present study suggest that the method for objectively evaluating skeletal
      maturation on cephalometric radiographs by determination of vertebral bone age
      can be applied to Brazilian females only. The development of a new method to
      objectively evaluate cervical vertebral bone age in males is needed.

PMID- 19089120
TI  - Fracture of abutment screw supporting a cemented implant-retained prosthesis with
      external hexagon connection: a case report with sem evaluation.
AB  - One of the causes of implant failures in cemented implant-retained prostheses is
      the fracture of abutment screw or UCLA abutment. This article reports a case of
      simultaneous fracture of two UCLA abutments screws occurring in an implant
      supported prosthesis placed in the mandibular molar region. The fractured
      structures were examined under scanning electron microscopy to investigate the
      probable causes of the failure, which were not related to failures on materials
      or fabrication of the screws, but rather were due to shear forces. The misfit in
      cemented prostheses may be the most likely cause of shear force generation.

PMID- 19089122
TI  - Antibiotic prophylaxis guidelines for infective endocarditis.

PMID- 19089121
TI  - Electromyographic activity assessment of individuals with and without
      temporomandibular disorder symptoms.
AB  - INTRODUCTION: Temporomandibular disorders (TMD) present several signs and
      symptoms that hinder their correct diagnosis, which is imperative on the
      elaboration of a treatment plan. Over the past years, several studies have been
      conducted to characterize and classify TMD to better understand these disorders.
      Therefore, the purpose of this study was to assess the electromyographic behavior
      of the masseter and temporal muscles in individuals with and without myogenic,
      arthrogenic and mixed TMD. METHOD: Forty volunteers of both genders responded to
      the Research Diagnostic Criteria for Temporomandibular Disorders (RDC-TMD)
      Questionnaire, were submitted to clinical exam and underwent bilateral
      electromyographic exam of the masseter and temporal muscles. RESULTS: No
      statistically significant difference (p>0.05) was observed during the assessment
      of isotonic contraction. Regarding isometric contraction, pairing between the
      mixed TMD group and the asymptomatic subjects did not present significant
      difference (p>0.05). Comparison between the myogenic and arthrogenic TMD groups
      and the asymptomatic group showed statistically significant difference (p<0.05).
      The findings of the present study demonstrated alteration on the muscle
      contraction pattern of TMD individuals compared to that of asymptomatic patients.

PMID- 19089123
TI  - Use of DNA technology in forensic dentistry.
AB  - The established importance of Forensic Dentistry for human identification, mainly
      when there is little remaining material to perform such identification (e.g., in
      fires, explosions, decomposing bodies or skeletonized bodies), has led dentists
      working with forensic investigation to become more familiar with the new
      molecular biology techniques. The currently available DNA tests have high
      reliability and are accepted as legal proofs in courts. This article presents a
      literature review referring to the main studies on Forensic Dentistry that
      involve the use of DNA for human identification, and makes an overview of the
      evolution of this technology in the last years, highlighting the importance of
      molecular biology in forensic sciences.

PMID- 19089124
TI  - Ultrastructural evaluation of the radioprotective effect of sodium selenite on
      submandibular glands in rats.
AB  - The aim of this study was to evaluate the radioprotector effect of sodium
      selenite on the ultrastructure of submandibular glands in rats. Fifty-seven male
      albino Wistar rats were randomized to 4 groups: control, irradiated, sodium
      selenite and irradiated/sodium selenite. The animals in the sodium selenite and
      irradiated/sodium selenite groups received intraperitoneal injections of sodium
      selenite (0.5 mg/kg body weight) 24 h before irradiation. The animals belonging
      to the irradiated and irradiated/sodium selenite groups were submitted to 15 Gy
      of gamma radiation in the head and neck region. The submandibular glands were
      removed at 4, 8, 12, 24, 48 and 72 h after irradiation. The ionizing radiation
      induced damage to the secretory cells, especially the serous cells, right from
      the first period. Vacuolization, lysis of cytoplasmic inclusions and nuclear
      alterations occurred. The sodium selenite group also presented cellular
      alterations in the study periods, but with less damage compared to that caused by
      radiation. There was greater similarity between the irradiated/sodium selenite
      group and the control group than with the other groups treated in all study
      periods. Despite the alterations observed in the sodium selenite group, sodium
      selenite presented a radioprotective action on the secretory cells of
      submandibular glands.

PMID- 19089125
TI  - Effect of cast rectifiers on the marginal fit of UCLA abutments.
AB  - OBJECTIVES: This study assessed the effect of cast rectifiers on the marginal
      misfit of cast UCLA abutments compared to premachined UCLA abutments. The
      influence of casting and porcelain baking on the marginal misfit of these
      components was also investigated. METHODS: Two groups were analyzed: test group -
      10 cast UCLA abutments, finished with cast rectifier and submitted to ceramic
      application; control group - 10 premachined UCLA abutments, cast with noble metal
      alloy and submitted to ceramic application. Vertical misfit measurements were
      performed under light microscopy. In the test group, measurements were performed
      before and after the use of cast rectifiers, and after ceramic application. In
      the control group, measurements were performed before and after casting, and
      after ceramic application. Data were submitted to statistical analysis by ANOVA
      and Tukey's test (a= 5%). RESULTS: The use of cast rectifiers significantly
      reduced the marginal misfit of cast UCLA abutments (from 25.68mm to 14.83mm;
      p<0.05). After ceramic application, the rectified cylinders presented misfit
      values (16.18mm) similar to those of premachined components (14.3 mm). Casting of
      the premachined UCLA abutments altered the marginal misfit of these components
      (from 9.63 mm to 14.6 mm; p<0.05). There were no significant changes after
      porcelain baking, in both groups. CONCLUSION: The use of cast rectifiers reduced
      the vertical misfit of cast UCLA abutments. Even with carefully performed
      laboratory steps, changes at the implant interface of premachined UCLA abutments
      occurred. Ceramic application did not alter the marginal misfit values of UCLA
      abutments.

PMID- 19089127
TI  - In vitro sealing ability of white and gray mineral trioxide aggregate (MTA) and
      white Portland cement used as apical plugs.
AB  - This study evaluated the sealing ability of apical plugs made of white and gray
      MTA-Angelus and white Portland cement placed via the root canal and having
      different thicknesses (2, 5 and 7 mm). Ninety extracted human single-rooted teeth
      were instrumented using a size 40 K-file to standardize the foraminal opening by
      the stepback technique. The teeth were assigned to 3 groups (n=30), according to
      the material used for fabrication of the apical plugs: A = gray MTA; B = white
      MTA; C = white Portland cement. The groups were subdivided into groups of 10
      teeth each according to the apical plug thickness (2, 5 and 7 mm). Marginal
      apical dye leakage was assessed using 0.2% Rhodamine B solution in which the
      specimens were immersed for 72 hours at 37 degrees C. The roots were sectioned
      longitudinally in a buccolingual direction for apical plug exposure, and digital
      photographs were taken and analyzed by Image Tool image-analysis software. Data
      were analyzed statistically by Kruskal-Wallis and Dunn's tests. Significance
      level was set at 5%. The least percent leakage was observed for 5- and 7-mm-thick
      plugs (p<0.05). No significant difference (p>0.05) was found between gray MTA and
      white Portland cement. Among the three materials analyzed, white MTA presented
      the highest marginal leakage (p<0.05). The findings of the present study showed
      that gray MTA and Portland cement had better sealing ability than white MTA when
      used as apical plugs. Dye leakage was smaller for 5- and 7-mm-thick plugs
      compared to 2-mm-thick plugs.

PMID- 19089126
TI  - Effect of a novel essential oil mouthrinse without alcohol on gingivitis: a
      double-blinded randomized controlled trial.
AB  - Several different plant extracts have been evaluated with respect to their
      antimicrobial effects against oral pathogens and for reduction of gingivitis.
      Given that a large number of these substances have been associated with
      significant side effects that contraindicate their long-term use, new compounds
      need to be tested. The aim of this study was to assess the short-term safety and
      efficacy of a Lippia sidoides ("alecrim pimenta")-based essential oil mouthrinse
      on gingival inflammation and bacterial plaque. Fifty-five patients were enrolled
      into a pilot, double-blinded, randomized, parallel-armed study. Patients were
      randomly assigned to undergo a 7-day treatment regimen with either the L.
      sidoides-based mouthrinse or 0.12% chlorhexidine mouthrinse. The results
      demonstrated decreased plaque index, gingival index and gingival bleeding index
      scores at 7 days, as compared to baseline. There was no statistically
      significance difference (p>0.05) between test and control groups for any of the
      clinical parameters assessed throughout the study. Adverse events were mild and
      transient. The findings of this study demonstrated that the L. sidoides-based
      mouthrinse was safe and efficacious in reducing bacterial plaque and gingival
      inflammation.

PMID- 19089128
TI  - Evaluation of the biocompatibility of root canal sealers using subcutaneous
      implants.
AB  - The purpose of this study was to evaluate in vivo the biocompatibility of
      Endomethasone, Pulp Canal Sealer EWT and AH-Plus root canal sealers after
      implantation in rat connective tissue. Twenty-four Wistar-Furth rats were used.
      Polyethylene tubes were filled with the sealers and implanted into specific
      dorsal subdermal tissue sites of the rats. Implants were removed after 3, 7 and
      30 days, fixed and processed for glycol methacrylate-embedding technique to be
      examined microscopically. On the 3rd day, there was a mild inflammatory reaction
      to Pulp Canal Sealer EWT implants, but a severe response to the other sealers
      with presence of acute inflammatory cells. On the 7th day, tissue organization
      was more evident with attenuation of the inflammatory reaction, especially for
      the AH-Plus implants. On the 30th day, connective tissue with few inflammatory
      cells was observed in contact with all sealer implants. In this time interval,
      the tissue in contact with Pulp Canal Sealer EWT implants was more organized,
      while the tissue close to Endomethasone and AH-Plus implants showed a mild
      persistent inflammatory reaction and had similar results to each other. In
      conclusion, the sealers had a similar pattern of irritation, which was more
      severe in the beginning and milder with time, in such a way that all sealers
      showed a persistent mild reaction. Pulp Canal Sealer EWT yielded better tissue
      organization than Endomethasone and AH-Plus, which, in turn, showed similar
      results to each other.

PMID- 19089129
TI  - Effect of storage period on the accuracy of elastomeric impressions.
AB  - AIMS: To investigate the effect of the storage period on the accuracy of recently
      developed elastomeric materials. METHODS: Simultaneous impressions of a steel die
      were taken using a polyether (I: Impregum Soft Heavy and Light body, 3M ESPE) and
      vinyl polysiloxane (P: Perfectim Blue Velvet and Flexi-Velvet, J.Morita). The
      trays were loaded with the heavy-bodied impression materials while the light
      bodied impression materials were simultaneously spread on the steel die. The
      impressions were poured after 2 hours, 24 hours, and 7 days. Impressions were
      stored at approximately 55% relative humidity and room temperature. Ten replicas
      were produced for each experimental condition (n=60). Accuracy of the stone dies
      was assessed with a depth-measuring microscope. The difference in height between
      the surface of the stone die and a standard metallic ring was recorded in
      micrometers at four demarcated points, by two independent examiners. Data were
      submitted to two-way ANOVA and Tukey test (a = 0.05). RESULTS: Significant
      differences were found among the groups. Smaller discrepancies were observed when
      pouring was performed up to 24 hours (I-2h= 65.0 +/- 15.68 microm; I-24h= 81.6 +/
      11.13 microm) for the polyether, and up to 7 days for the vinyl polysiloxane (P
      2h= 79.1 +/- 13.82 microm; P-24h= 96.8 +/- 6.02 microm; P-7d= 81.4 +/- 4.3
      microm). Significant dimensional discrepancies, however, were observed when
      polyether was stored for 7 days (I-7d= 295.3 +/- 17.4 microm). CONCLUSION:
      Storage may significantly affect the dimensional accuracy of impressions and,
      thus, a maximum period and storage condition should be specified for the recently
      developed materials.

PMID- 19089130
TI  - Influence of isolated cleft palate and palatoplasty on the face.
AB  - INTRODUCTION: The literature has demonstrated that alterations in craniofacial
      morphology characterizing individuals with cleft palate are observed in both
      operated and unoperated patients. OBJECTIVE: This study evaluated the influence
      of isolated cleft palate and palatoplasty on the face, based on facial analysis.
      MATERIAL AND METHODS: Lateral facial photographs of the right side of 85 young
      adult patients with cleft palate were analyzed, of whom 50 were operated on and
      35 had never received any previous surgical treatment. The nasolabial angle and
      zygomatic projection were used to define the maxillary position in the face.
      Mandibular positioning was classified as Pattern I, II and III. RESULTS: Patients
      were distributed into 54.12% as Pattern I, 32.94% Pattern II and 12.94% Pattern
      III. Distribution of facial patterns did not show statistically significant
      differences between groups (p>0.05). Although palatoplasty did not influence the
      facial pattern, the zygomatic projection was vulnerable to plastic surgeries.
      Twenty-eight percent of the patients in the operated group showed zygomatic
      deficiency, compared to only 8.5% in the unoperated group. CONCLUSIONS: In
      patients with isolated cleft palate, palatoplasty may influence negatively the
      sagittal behavior of the maxilla, according to the zygomatic projection of the
      face, though without compromising the facial pattern.

PMID- 19089131
TI  - Fluoride concentrations in industrialized beverages consumed by children in the
      city of Bauru, Brazil.
AB  - The increasing consumption of juices, soft drinks and teas among children has
      increased significantly fluoride ingestion at the age range of risk for
      development of dental fluorosis. OBJECTIVE: The purpose of this study was to
      evaluate fluoride concentrations in some brands of industrialized beverages
      consumed by children in the city of Bauru, SP, Brazil. MATERIAL AND METHODS: 98
      brands of beverages were analyzed, divided into 3 lots, comprising 36, 32 and 30
      brands, respectively, for the first, second and third lots. Fluoride
      concentrations were determined by HMDS-facilitated diffusion, using a fluoride
      ion-specific electrode (Orion 9409). RESULTS: Fluoride concentrations ranged
      between 0.04 and 1.76 microg F/mL. It was observed a wide variation in fluoride
      concentrations among the different brands, as well as the different lots of the
      same brand. There was no information on fluoride concentrations on the labels of
      any product. CONCLUSIONS: Some of the products analyzed could contribute
      significantly to the total fluoride intake and, thus, be important risk factors
      for development of dental fluorosis, which indicates the need of controlling the
      production of these beverages with respect to fluoride concentration.

PMID- 19089132
TI  - Humoral immune response to antigens of Porphyromonas gingivalis ATCC 33277 in
      chronic periodontitis.
AB  - INTRODUCTION: Periodontitis is a chronic disease that results from an interaction
      of a mixed bacterial challenge and the host response. OBJECTIVE: The purposes of
      this study were to evaluate the IgG serum levels to Porphyromonas gingivalis
      antigens by ELISA in individuals with different periodontal conditions correlated
      with clinical parameters, and to analyze the immunoreactivity profiles by Western
      blotting. METHODS: Serum IgG levels against the cell sonicate antigen from P.
      gingivalis ATCC 33277 of 28 patients with chronic periodontitis (CP), 10 patients
      with gingivitis (G) and 21 periodontally healthy individuals (H) were measured by
      ELISA and Western immunoblotting. RESULTS: In the CP group, sera reactivity by
      ELISA was significantly higher than in the G and H groups (Kruskal-Wallis
      p<0.001; Dunnet t3 p= 0.001 and Dunnet t3 p= 0.0001). There was no statistically
      significant difference between G and HP reactivity (Dunnett t3 p=0.617). Among
      individuals with chronic periodontitis, the IgG-anti-P. gingivalis serum levels
      were positively correlated with percentage of clinical attachment level =5mm (r s
      = + 0.375, p<0.05) and a negative correlation was found between IgG-anti-P.
      gingivalis levels and percentage of probing pocket depth 0-3mm (r s = - 0. 411,
      p< 0.05). The analysis of sera immunoreactivity profiles to sonicate antigen by
      Western blotting showed differences between the sera of CP, G and H group
      individuals. The serum from CP frequently reacted with high molecular weight (103
      kDa, 86 kDa, 72 kDa, 60 kDa, 58 kDa, 52 kDa) protein fractions. CONCLUSIONS:
      Serum levels of IgG anti-P. gingivalis distinguished individuals with chronic
      periodontitis, gingivitis and healthy periodontium. There was a correlation
      between clinical parameters and serum IgG levels against P. gingivalis. There was
      a difference in the recognition profile of protein fractions among the studied
      groups and some bands were more specific.

PMID- 19089133
TI  - Comparative study of single and multislice computed tomography for assessment of
      the mandibular canal.
AB  - OBJECTIVE: The purpose of this study was to evaluate the accuracy of relative
      measurements from the roof of the mandibular canal to the alveolar crest in
      multislice (multidetector) computed tomography (MDCT) and single-slice computed
      tomography (SSCT). MATERIAL AND METHODS: The sample consisted of 26 printed CT
      films (7 SSCT and 19 MDCT) from the files of the LABI-3D (3D Imaging Laboratory)
      of the School of Dentistry of the University of Sao Paulo (FOUSP), which had been
      acquired using different protocols. Two observers analyzed in a randomized and
      independent order a series of 22 oblique CT reconstructions of each patient. Each
      observer analyzed the CT scans twice. The length of the mandibular canal and the
      distance between the mandibular canal roof and the crest of the alveolar ridge
      were obtained. Dahlberg test was used for statistical analysis. RESULTS: The mean
      error found for the mandibular canal length measurements obtained from SSCT was
      0.53 mm in the interobserver analysis, and 0.38 mm for both observers. On MDCT
      images, the mean error was 0.0 mm in the interobserver analysis, and 0.0 and 0.23
      mm in the intraobserver analysis. Regarding the distance between the mandibular
      canal roof and the alveolar bone crest, the SSCT images showed a mean error of
      1.16 mm in the interobserver analysis and 0.66 and 0.59 mm in the intraobserver
      analysis. In the MDCT images, the mean error was 0.72 mm in the interobserver
      analysis and 0.50 and 0.54 mm in the intraobserver analysis. CONCLUSION:
      Multislice CT was demonstrated a more accurate method and demonstrated high
      reproducibility in the analysis of important anatomical landmarks for planning of
      mandibular dental implants, namely the mandibular canal pathway and alveolar
      crest height.

PMID- 19089134
TI  - Association between intra-radicular posts and periapical lesions in
      endodontically treated teeth.
AB  - INTRODUCTION: A significant number of endodontically treated teeth restored with
      posts have associated periapical lesions, and several authors have discussed the
      probable causes of the development of these. Attention has been focused on
      restorative procedures performed after endodontic treatment and their association
      with the prognosis of endodontic therapy because a number of root-filled teeth
      will require post- and core-retained restorations. PURPOSE: The purpose of this
      study was to evaluate, by examination of periapical radiographs, whether the
      placement of intra-radicular posts in endodontically treated teeth may act as a
      risk factor for development of periapical lesions. MATERIAL AND METHODS: This
      case-control study analyzed periapical radiographs of 72 endodontically treated
      teeth with coronal restorations. All radiographs were obtained from a single
      private practice. Specimens were assigned to 2 groups: Group 1 (control) was
      composed of teeth without periapical lesions and Group 2 (case) was composed of
      teeth with periapical lesions. The number of teeth with and without posts in each
      group was recorded. Three calibrated examiners analyzed the radiographs visually
      under X4 magnification. RESULTS: In Group 1, 28 (65.1%) out of 43 teeth were
      restored with posts. In Group 2, 24 (82.8%) out of 29 teeth had intra-radicular
      posts. The interpretation of chi-square test showed that these percentages were
      not significantly different (x(2)=2.687; p=0.101). Odds ratio was 2.571 (0.815
      8.118), which indicates that there was no statistically significant association
      between periapical lesions and posts. CONCLUSION: Intra-radicular posts placed in
      endodontically treated teeth were not a significant risk factor for development
      of periapical lesions in the practice where the cohort of patients was treated.

PMID- 19089135
TI  - Effect of acid etching of glass ionomer cement surface on the microleakage of
      sandwich restorations.
AB  - The purposes of this study were to evaluate the sealing ability of different
      glass ionomer cements (GICs) used for sandwich restorations and to assess the
      effect of acid etching of GIC on microleakage at GIC-resin composite interface.
      Forty cavities were prepared on the proximal surfaces of 20 permanent human
      premolars (2 cavities per tooth), assigned to 4 groups (n=10) and restored as
      follows: Group CIE - conventional GIC (CI) was applied onto the axial and
      cervical cavity walls, allowed setting for 5 min and acid etched (E) along the
      cavity margins with 35% phosphoric acid for 15 s, washed for 30 s and water was
      blotted; the adhesive system was applied and light cured for 10 s, completing the
      restoration with composite resin light cured for 40 s; Group CIN - same as Group
      CIE, except for acid etching of the CI surface; Group RME - same as CIE, but
      using a resin modified GIC (RMGIC); Group RMN - same as Group RME, except for
      acid etching of the RMGIC surface. Specimens were soaked in 1% methylene blue dye
      solution at 24 degrees C for 24 h, rinsed under running water for 1 h, bisected
      longitudinally and dye penetration was measured following the ISO/TS 11405-2003
      standard. Results were statistically analyzed by Kruskal-Wallis and chi-square
      tests (a=0.05). Dye penetration scores were as follow: CIE - 2.5; CIN - 2.5; RME 
      0.9; and RMN - 0.6. The results suggest that phosphoric acid etching of GIC
      prior to the placement of composite resin does not improve the sealing ability of
      sandwich restorations. The RMGIC was more effective in preventing dye penetration
      at the GIC-resin composite-dentin interfaces than CI.

PMID- 19089136
TI  - Perceived dental anxiety among schoolchildren treated through three caries
      removal approaches.
AB  - OBJECTIVES: The aim of the investigation was to test the differences in the
      perceived level of dental anxiety among children treated restoratively using the
      Atraumatic Restorative Treatment (ART) approach, the traditional restorative
      (TRA) approach and ART aided with a chemomechanical caries removal gel (ART
      plus). METHODS: The study subjects were 6-7-year-old children. TRA was compared
      to ART in a clinical setting after children had seen a dentist twice (Group A),
      ART was compared to 'ART plus' in a clinical setting after children had seen a
      dentist once (Group B) and ART was applied outside the clinic on school premises
      (Group C). The treatments were carried out in Class II cavitated dentine lesion
      in primary molars. Dental anxiety was measured using the Venham Picture Test
      (VPT). Three-way analysis of variances and interaction was applied to test for
      treatment approach, gender and operator effects on the mean VPT scores. RESULTS:
      There was no statistically significant difference (p=0.80) observed between the
      mean VPT scores for the traditional approach and those for the ART approach and
      between ART with and without a chemomechanical caries removal gel (p=0.07).
      Children in Group A had lower mean VPT scores than children in Group B (p=0.02)
      and Group C (p<0.00001) when treated using the ART approach by the same two
      operators. CONCLUSIONS: The level of dental anxiety was low. There was no
      difference in level of dental anxiety observed in children treated with ART in
      comparison to the traditional restorative approach, and between children treated
      with ART with and without a chemomechanical caries removal gel. The treatment
      environment and prepatory visits may be factors determining the level of dental
      anxiety in children treated through the ART approach only.

PMID- 19089137
TI  - In vitro evaluation of the precision of working casts for implant-supported
      restoration with multiple abutments.
AB  - OBJECTIVE: The purpose of this study was to compare the accuracy of two working
      cast fabrication techniques using strain-gauge analysis. METHODS: Two working
      cast fabrication methods were evaluated. Based on a master model, 20 working
      casts were fabricated by means of an indirect impression technique using
      polyether after splinting the square transfer copings with acrylic resin.
      Specimens were assigned to 2 groups (n=10): Group A (GA): type IV dental stone
      was poured around the abutment analogs in the conventional way; Group B (GB), the
      dental stone was poured in two stages. Spacers were used over the abutment
      analogs (rubber tubes) and type IV dental stone was poured around the abutment
      analogs in the conventional way. After the stone had hardened completely, the
      spacers were removed and more stone was inserted in the spaces created. Six
      strain-gauges (Excel Ltd.), positioned in a cast bar, which was dimensionally
      accurate (perfect fit) to the master model, recorded the microstrains generated
      by each specimen. Data were analyzed statistically by the variance analysis
      (ANOVA) and Tukey's test (I+/-= 5%). RESULTS: The microstrain values
      (microepsilon) were (mean+/-SD): GA: 263.7+/-109.07microepsilon, and GB: 193.73+/
      78.83microepsilon. CONCLUSION: There was no statistical difference between the
      two methods studied.

PMID- 19089138
TI  - Editorial.

PMID- 19089139
TI  - Internal adaptation of cast titanium crowns.
AB  - As the adaptation of titanium crowns obtained by Rematitan Plus investment,
      specific for titanium, is not recognized to be suitable, this study evaluated the
      effect of the concentration of the specific liquid and the temperature of the
      mold of investments on the internal misfit of crowns cast on commercially pure
      titanium. Individual dies of epoxy resin were obtained, representing teeth
      prepared for full-crown restoration with a 6-degree axial surface convergence
      angle and shoulder (1.0 mm). For the waxing of each crown, a ring-shaped
      stainless steel matrix (8.0mm internal diameter; 7.5 mm height) was adapted above
      the individual dies of epoxy resin. The Rematian Plus investment was mixed
      according to the manufacturer's instructions using two different concentrations
      of the specific liquid: 100%, 75%. Casting was performed in a Discovery Plasma Ar
      arc vacuum-pressure casting machine with molds at temperatures of 430 degrees C,
      515 degrees C and 600 degrees C. The crowns were cleaned individually in a
      solution (1% HF + 13% HNO3) for 10 min using a ultrasonic cleaner, with no
      internal adaptations, and luted with zinc phosphate cement under a 5 kg static
      load. The crown and die assemblies were embedded in resin and sectioned
      longitudinally. The area occupied by cement was observed using stereoscopic lens
      (10X) and measured by the Leica Qwin image analysis system (mm(2)). The data for
      each experimental condition (n=8) were analyzed by Kruskal-Wallis non-parametric
      test (a=0.05). The results showed that liquid dilution and the increase in mold
      temperature did not significantly influence the levels of internal fit of the
      cast titanium crowns. The lowest means (+/-SD) of internal misfit were obtained
      for the 430 degrees C/100%: (7.25 mm(2) +/-1.59) and 600 degrees C/100% (8.8
      mm(2) +/-2.25) groups, which presented statistically similar levels of internal
      misfit.

PMID- 19089140
TI  - Polarization of dental caries among individuals aged 15 to 18 years.
AB  - OBJECTIVE: To evaluate the role of socioeconomic variables and self-perceived
      oral health in the polarization of caries among adolescents in Santa Barbara
      D'Oeste, Brazil. MATERIAL AND METHODS: Cross-sectional study. Sampling was
      randomized and sample size was defined according to WHO criteria. Two hundred and
      seventy seven adolescents (15 to 18 year-old) were examined by five trained
      examiners that assessed DMFT index according to WHO criteria. Self-perceived oral
      health, access to dental services and socio-demographic variables were self
      reported. Student's t tests, chi-square tests, and multivariate logistic
      regression (with significant caries index (SiC) as the outcome), were performed.
      RESULTS: Mean DMFT was 5.48 (+/-4.22) and the proportion of "caries free"
      subjects was 15.5%. Mean DMFT (9.71+/-2.85) and mean D (1.67+/-2.18) of SiC
      positive subjects were significantly higher than mean DMFT (2.88+/-2.17) and mean
      D (0.45+/-0.87) of SiC negative subjects (p<0.0001). Mean D of white (0.76+/
      1.51) was significantly smaller than mean D of non-white subjects (1.32+/-2.01).
      The only variable independently associated with the "SiC positive" outcome was
      "report of toothache within six months prior to the study" [OR=1.83 (95%CI 1.08
      to 3.12)], p<0.001. CONCLUSION: SiC was associated with "report of toothache" but
      not with socio-demographic variables in the studied population.

PMID- 19089141
TI  - Cervical spine signs and symptoms: perpetuating rather than predisposing factors
      for temporomandibular disorders in women.
AB  - AIM: The purpose of this study was to assess in a sample of female community
      cases the relationship between the increase of percentage of cervical signs and
      symptoms and the severity of temporomandibular disorders (TMD) and vice-versa.
      MATERIAL AND METHODS: One hundred women (aged 18-26 years) clinically diagnosed
      with TMD signs and symptoms and cervical spine disorders were randomly selected
      from a sample of college students. RESULTS: 43% of the volunteers demonstrated
      the same severity for TMD and cervical spine disorders (CSD). The increase in TMD
      signs and symptoms was accompanied by increase in CSD severity, except for pain
      during palpation of posterior temporal muscle, more frequently observed in the
      severe CSD group. However, increase in pain during cervical extension, sounds
      during cervical lateral flexion, and tenderness to palpation of upper fibers of
      trapezius and suboccipital muscles were observed in association with the
      progression of TMD severity. CONCLUSION: The increase in cervical symptomatology
      seems to accompany TMD severity; nonetheless, the inverse was not verified. Such
      results suggest that cervical spine signs and symptoms could be better recognized
      as perpetuating rather than predisposing factors for TMD.

PMID- 19089142
TI  - Adhesives with different pHs: effect on the MTBS of chemically activated and
      light-activated composites to human dentin.
AB  - PURPOSE: To evaluate the bond strength between human dentin and composites, using
      two light-activated single-bottle total-etch adhesive systems with different pHs
      combined with chemically activated and light-activated-composites. The tested
      hypothesis was that the dentin bond strength is not influenced by an adhesive
      system of low pH, combined with chemically activated or light-activated
      composites. MATERIAL AND METHOD: Flat dentin surfaces of twenty-eight human third
      molars were allocated in 4 groups (n=7), depending on the adhesive system: (One
      Step Plus-OS and Prime & Bond NT-PB) and composite (light-activated Filtek Z-100
      [Z100] and chemically activated Bisfil 2B [B2B]). Each adhesive system was
      applied on acid-etched dentin and then one of the composites was added to form a
      5 mm-high resin block. The specimens were stored in tap water (37 degrees C/24 h)
      and sectioned into two axes, x and y. This was done with a diamond disk under
      coolant irrigation to obtain beams with a cross-section area of approximately 0.8
      mm(2). Each specimen was then attached to a custom-made device and submitted to
      the microtensile test (1 mm*min-1). Data were analyzed using two-way ANOVA and
      Tukey's tests (p<0.05). RESULTS: The anticipated hypothesis was not confirmed
      (p<0.0001). The bond strengths (MPa) were not statistically different between the
      two adhesive systems when light-activated composite was used (OS+Z100 = 24.7+/
      7.1 feminine; PB+Z100 = 23.8+/-5.7 feminine). However, with use of the chemically
      activated composite (B2B), PB (7.8+/-3.6b MPa) showed significantly lower dentin
      bond strengths than OS (32.2+/-7.6 feminine). CONCLUSION: The low pH of the
      adhesive system can affect the bond of chemically activated composite to dentin.
      On the other hand, under the present conditions, the low pH did not seem to
      affect the bond of light-activated composites to dentin significantly.

PMID- 19089143
TI  - Analysis of gap formation at tooth-composite resin interface: effect of C-factor
      and light-curing protocol.
AB  - OBJECTIVE: The aim of this study was to evaluate the effect of C-factor and light
      curing protocol on gap formation in composite resin restorations. MATERIAL AND
      METHODS: Cylindrical cavities with 5.0 mm diameter and three different depths
      (A=1.0, B=2.0 and C=3.0 mm) were prepared on the occlusal surface of 30 human
      molars and restored in a single increment with P 60. The composite resin was
      light-cured according to two protocols: standard - 850 mW/cm(2) / 20 s and
      gradual - 100 up to 1000 mW/cm(2) / 10 s + 1000 mW/cm(2) / 10 s. After storage in
      distilled water (37 degrees C/7 days), the restorations were cut into three
      slices in a buccolingual direction and the gap widths were analyzed using a 3D
      scanning system. The data were submitted to ANOVA and Student-Newman-Keuls test
      (alpha=0.05). RESULTS: ANOVA detected a significant influence for the C-factor
      and light-curing protocol as independent factors, and for the double interaction
      C-factor vs. light-curing protocol. Cavities with higher C-factor presented the
      highest gap formation. The gradual light-curing protocol led to smaller gap
      formation at cavity interfaces. CONCLUSIONS: The findings of this study suggest
      that the C-factor played an essential role in gap formation. The gradual light
      curing protocol may allow relaxation of composite resin restoration during
      polymerization reaction.

PMID- 19089144
TI  - Evaluation of the reproducibility of two techniques used to determine and record
      centric relation in angle's class I patients.
AB  - The centric relation is a mandibular position that determines a balance relation
      among the temporomandibular joints, the chew muscles and the occlusion. This
      position makes possible to the dentist to plan and to execute oral rehabilitation
      respecting the physiological principles of the stomatognathic system. The aim of
      this study was to investigate the reproducibility of centric relation records
      obtained using two techniques: Dawson's Bilateral Manipulation and Gysi's Gothic
      Arch Tracing. Twenty volunteers (14 females and 6 males) with no dental loss,
      presenting occlusal contacts according to those described in Angle's I
      classification and without signs and symptoms of temporomandibular disorders were
      selected. All volunteers were submitted five times with a 1-week interval, always
      in the same schedule, to the Dawson's Bilateral Manipulation and to the Gysi's
      Gothic Arch Tracing with aid of an intraoral apparatus. The average standard
      error of each technique was calculated (Bilateral Manipulation 0.94 and Gothic
      Arch Tracing 0.27). Shapiro-Wilk test was applied and the results allowed
      application of Student's t-test (sampling error of 5%). The techniques showed
      different degrees of variability. The Gysi's Gothic Arch Tracing was found to be
      more accurate than the Bilateral Manipulation in reproducing the centric relation
      records.

PMID- 19089145
TI  - Surgical crown lengthening: a 12-month study - radiographic results.
AB  - OBJECTIVE: The purpose of this study was to perform a radiographic follow-up
      evaluation after a 12-month healing period, following crown lengthening surgery.
      MATERIAL AND METHODS: Twenty-three periodontally healthy subjects (mean age 32.5
      years) that required crown lengthening surgery in premolars were recruited. In a
      total of 30 premolars, full thickness flaps, osseous resection, and flap suturing
      were performed. The restorative margin was defined in the pre-surgical phase and
      maintained unaltered during the healing period, serving as a reference point.
      Standardized bitewing radiographs were taken before and after osseous reduction,
      and at 2, 3, 6, and 12-month healing periods. RESULTS: Intact lamina dura was
      observed at both mesial and distal alveolar crests only from the 3rd month. At 12
      months, all alveolar crests presented lamina dura. The overall mean distance from
      the restorative margin to the alveolar crest achieved after osseous resection was
      3.28+/-0.87 mm at mesial and 2.81+/-0.51 mm at distal sites. No significant
      radiographic changes in the bone crest were observed during a 12-month healing
      period. CONCLUSION: The findings of this study suggest that the radiographic
      proximal bone level observed on bitewing radiographs following crown lengthening
      surgery can be used as a reference to predict the future level of the healed
      alveolar crest.

PMID- 19089146
TI  - Nanoleakage phenomenon on deproteinized human dentin.
AB  - OBJECTIVE: The purpose of this study was to evaluate the influence of dentin
      deproteinization on the nanoleakage phenomenon. MATERIAL AND METHODS: Class V
      cavities were prepared in 12 human molars with cervical margins located in
      dentin. The cavities were assigned to 2 groups (n=6) according to dentin
      treatment: Group I - dentin treated in accordance with the manufacturer's
      instructions and Group II - dentin treated following the manufacturer's
      instructions + 10% NaOCl. Each group was sub-divided into three groups, according
      to the DBS (dentin bonding system) used: Scotchbond Multi Purpose (SBMP), Prime &
      Bond NT (PB) and Clearfil SE Bond (SE), which were applied according to
      manufacturer's instructions. The cavities were restored with composite resin, and
      the specimens were immersed in a tracer agent (AgNO3 50%) for 24 h. The teeth
      were sectioned buccolingually through the center of the restorations, and
      nanoleakage pattern was evaluated by scanning electron microscopy (SEM) using the
      backscattered electron image mode. RESULTS: SEM analysis showed different
      nanoleakage patterns for each DBS. Irrespective of dentin treatments, all SBMP
      specimens showed nanoleakage. SE did not show any nanoleakage with both dentin
      treatments used. PB showed nanoleakage within the hybrid layer only in Group I.
      CONCLUSIONS: The influence of dentin deproteinization on the nanoleakage
      phenomenon was dependent on dentin bonding system formulation and bonding
      strategies.

PMID- 19089147
TI  - Ultrastructural and immunohistochemical study of the influence of fluoride excess
      on the development of rat incisor tooth buds.
AB  - Little information is available on the pathogenesis of fluorosis during the fetal
      and initial postnatal period. In the present study, female rats received 0
      (control), 7 or 100 ppm of sodium fluoride in drinking water, one week before
      breeding and throughout gestation and nursing periods. The hemimandibles of the
      offspring were collected at 0, 7 and 14 days of postnatal life (n = 5) and
      processed for morphological analyses by light and electron microscopy,
      immunohistochemical analysis for amelogenin and morphometric study of enamel
      matrix and ameloblasts of incisors. The results showed a decrease in matrix
      production at the secretory phase at all study periods for the 100 ppm group. In
      this same group, the secretory ameloblasts showed reduction of enamel matrix
      secretion, disorganization of mitochondrial crests, large vacuoles at the apical
      portion of the cytoplasm, retention of intracisternal material and dilatation of
      some cisterns in the rough endoplasmic reticulum. In the groups of animals aged 7
      and 14 days, analysis of variance showed significant reduction (p<0.05) in
      cytoplasmic volume of 23.80% and 24.75%, respectively, in relation to the control
      group. The smooth-ended maturation ameloblasts exhibited a large number of
      vacuoles with electron-dense endocytic matrix, suggesting a delay in the
      resorption process. Immunohistochemical analysis showed no difference in the
      intensity and labeling pattern of the enamel matrix in any study group.
      Interestingly, in offspring at the age of 14 days for the 7 ppm group, there was
      an increase in the matrix length at the secretory phase. Therefore, part of the
      excessive dose of sodium fluoride given to the mother in drinking water can reach
      the offspring through the placenta and mother's milk, causing morphological
      changes in ameloblasts and suggesting a reduction in secretion and a delay in
      matrix resorption.

PMID- 19089148
TI  - Compressive fatigue in titanium dental implants submitted to fluoride ions
      action.
AB  - The aim of this study was to assess the influence of a fluoridated medium on the
      mechanical properties of an internal hexagon implant-abutment set, by means of
      compression, mechanical cycling and metallographic characterization by scanning
      electronic microscopy. Five years of regular use of oral hygiene with a sodium
      fluoride solution content of 1500 ppm were simulated, immersing the samples in
      this medium for 184 hours, with the solutions being changed every 12 hours. Data
      were analyzed at a 95% confidence level with Fisher's exact test. After the
      action of fluoride ions, a negative influence occurred in the mechanical cycling
      test performed in a servohydraulic machine (Material Test System-810) set to a
      frequency of 15 Hz with 100,000 cycles and programmed to 60% of the maximum
      resistance of static compression test. The sets tended to fracture by compression
      on the screw, characterized by mixed ruptures with predominance of fragile
      fracture, as observed by microscopy. An evidence of corrosion by pitting on
      sample surfaces was found after the fluoride ions action. It may be concluded
      that prolonged contact with fluoride ions is harmful to the mechanical properties
      of commercially pure titanium structures.

PMID- 19089149
TI  - Microhardness of composite resins at different depths varying the post
      irradiation time.
AB  - OBJECTIVE: The purpose of this study was to assess the microhardness of posterior
      composite resins at different depths varying the post-irradiation time. MATERIALS
      AND METHODS: For each composite resin [Solitaire 2 (SO) - Heraus Kulzer, P60 (P) 
      3M, Prodigy Condesable (PC) - Kerr, Surefil (S) - Dentsply and Alert (A) -
      Pentron], 6 specimens (3 mm in diameter; 4 mm high) were prepared using a black
      polyurethane cylindrical matrix. The resins were inserted in a bulk increment and
      light cured for 40 seconds. Microhardness was analyzed at different depths (top,
      0.4 mm, 1.0 mm, 2.0 mm, 3.0 mm and 4.0 mm) and at two moments (20 minutes and 24
      hours after light-curing). Data were analyzed by ANOVA and Tukey's test (p<0.05).
      RESULTS: Overall, microhardness means decreased significantly with the increase
      of depth, being lower in the first moment tested. P, S and PC showed the highest
      microhardness means. CONCLUSION: It may be concluded that the tested composite
      resins presented a gradual decrease of microhardness as depth increased and this
      drop was more accentuated for depths beyond 2 mm. For all materials, higher
      microhardness means were recorded 24 hours after light activation. P60 yielded
      the best results at the different depths evaluated.

PMID- 19089150
TI  - Central giant cell granuloma of the jaws and giant cell tumor of long bones: an
      immunohistochemical comparative study.
AB  - OBJECTIVE: This study investigated whether some components of the extracellular
      matrix and CD68 expression may drive the differences between the central giant
      cell granuloma (CGCG) of the jaws and giant cell tumor (GCT) of long bones, which
      present distinct evolution and clinical behavior. MATERIAL AND METHODS: Eight
      cases of CGCG and 7 cases of GCT were selected and immunohistochemically analyzed
      to verify the pattern of expression of CD68, tenascin (Tn) and fibronectin (Fn).
      RESULTS: A large number of the mononuclear cells and multinucleated giant cells
      CD68+ was observed in both of the studied lesions, indicating histiocyte/
      macrophage origin. Seven cases of CGCG of the jaws showed intense staining of Fn,
      with uniform distribution predominantly. In all 7 cases of GCT of long bones the
      Fn displayed intense expression, with distribution pattern varying from uniform
      to reticulate/fibrillar. Six cases of CGCG were intensively stained by Tn,
      presenting focal expression in half of specimens, and reticulate/ fibrillar
      pattern of expression in 4 cases. All cases of GCT of the long bones presented
      intense expression of Tn, uniform distribution, and reticulate/fibrillar pattern
      of expression in four cases. CONCLUSIONS: The immunoexpression of CD68 in
      mononuclear cells and multinucleated giant cells and staining patterns of Fn and
      Tn were similar in both entities. These findings indicate that these proteins
      could not be used to explain the differences between the CGCG of the jaws and GCT
      of the long bones.

PMID- 19089151
TI  - Lysanda paste: a new option for root-end filling.
AB  - This study aimed to compare the apical sealing of root-end fillings performed
      with Lysanda (zinc oxide-eugenol paste) with radiopacifiers (iodoform or zinc
      oxide) and calcium hydroxide. Root-end cavities were prepared and filled with
      different materials, as follows: Group I - Lysanda paste with iodoform; Group II 
      Lysanda paste with iodoform and calcium hydroxide; Group III - Lysanda paste
      with iodoform and zinc oxide; Group IV - Lysanda paste with zinc oxide; Group V -
      mineral trioxide aggregate (MTA). After filling, the teeth were immersed in 2%
      methylene blue for analysis of marginal leakage. It was observed that marginal
      leakage occurred in all groups. Lysanda paste with iodoform showed the lowest
      leakage, with no statistically significant difference compared to the other
      groups. All materials can be considered as good options for root-end filling.

PMID- 19089152
TI  - Localized mechanics of dentin self-etching adhesive system.
AB  - The bond strength of composite resins (CRs) to dentin is influenced by the
      interfacial microstructure of the hybrid layer (HL) and the resin tags (TAG). The
      contemporary self-etching primer adhesive systems overcame the inconvenient of
      the etch-and-rinse protocol. Studies, however, have demonstrated that HL
      thickness and TAG length vary according to the wetting time and additional use of
      acid-etching prior to self-etching primers. This study investigated the localized
      stress distribution in the HL and the dentin/adhesive interface. Two HL
      thicknesses (3 or 6 microm), two TAG lengths (13 or 17 microm) and two loading
      conditions (perpendicular and oblique-25 degrees) were investigated by the finite
      element (FE) analysis. Five two-dimensional FE models (M) of a dentin specimen
      restored with CR (38 x 64 microm) were constructed: M1 - no HL and no TAG; M2 - 3
      microm of HL and 13 microm of TAG; M3 - 3 microm of HL and 17 microm of TAG; M4 -
      6 microm of HL and 13 microm of TAG; and M5 - 6 microm of HL and 17 microm of
      TAG. Two distributed loadings (L) (20N) were applied on CR surface: L1 -
      perpendicular, and L2 - oblique (25 masculine). Fixed interfacial conditions were
      assigned on the border of the dentin specimen. Ansys 10.0 (Ansys, Houston, PA,
      USA) software was used to calculate the stress fields. The peak of von Mises
      (sigma(vM)) and maximum principal stress (sigma(max)) was higher in L2 than in
      L1. Microstructures (HL and TAG) had no effect on local stresses for L1.
      Decreasing HL decreased sigma(vM) and sigma(max) in all structures for L2, but
      the TAG length had influence only on the peributular dentin. The thickness of HL
      had more influence on the sigma(vM) and sigma(max) than TAG length. The
      peritubular dentin and its adjacent structures showed the highest sigma(vM) and
      sigma(max), mainly in the oblique loading.

PMID- 19089153
TI  - Dental wear caused by association between bruxism and gastroesophageal reflux
      disease: a rehabilitation report.
AB  - Bruxism is a pathological activity of the stomatognathic system that involves
      tooth grinding and clenching during parafunctional jaw movements. Clinical signs
      of bruxism are mostly related to dental wear and muscular and joint discomforts,
      but a large number of etiological factors can be listed, as local, systemic,
      psychological and hereditary factors. The association between bruxism, feeding
      and smoking habits and digestive disorders may lead to serious consequences to
      dental and related structures, involving dental alterations (wear, fractures and
      cracks), periodontal signs (gingival recession and tooth mobility) and muscle
      joint sensitivity, demanding a multidisciplinary treatment plan. This paper
      presents a case report in which bruxism associated with acid feeding, smoking
      habit and episodes of gastric reflow caused severe tooth wear and great muscular
      discomfort with daily headache episodes. From the diagnosis, a multidisciplinary
      treatment plan was established. The initial treatment approach consisted of
      medical follow up with counseling on diet and smoking habits and management of
      the gastric disorders. This was followed by the installation of an interocclusal
      acrylic device in centric relation of occlusion (CRO) for reestablishment of the
      occlusal stability, vertical dimension of occlusion, anterior guides and return
      to normal muscle activity (90-day use approximately). After remission of initial
      symptoms, oral rehabilitation was implemented in CRO by means of full resin
      composite restorations and new interocclusal device for protection of
      restorations. Satisfactory esthetics, improved function and occlusal stability
      were obtained after oral rehabilitation. The patient has attended annual follow
      ups for the past 2 years. The multidisciplinary treatment seems to be the key for
      a successful rehabilitation of severe cases of dental wear involving the
      association of different health disorders.

PMID- 19089164
TI  - Editorial.

PMID- 19089165
TI  - Association between polymorphism in the promoter region (G/C-915) of PAX9 gene
      and third molar agenesis.
AB  - PURPOSE: Hypodontia is the congenital absence of one or more (up to six)
      permanent and/or deciduous teeth, being one of the most common alterations of the
      human dentition. Genetic polymorphisms are variations of DNA sequences occurring
      in a population. This study investigated whether G-915C single nucleotide
      polymorphism (SNPs) in the PAX9 gene promoter is associated with hypodontia in
      humans. MATERIAL AND METHODS: The polymorphism in region G/C-915 of PAX9 gene
      (NCBI ref SNP ID: rs 2073247) of 240 patients was analyzed, being 110 controls
      and 130 individuals with third molar agenesis. After DNA extraction, the region
      of interest was amplified by PCR technique using two different primers. The
      significance of the differences in observed frequencies of polymorphisms in both
      groups was assessed by odds-ratio and chi-squared test with 95% confidence
      interval. RESULTS: Genotype CC was more frequent in patients with agenesis
      (11.5%) compared to the control (1.8%), while GG was more prevalent in the
      control group (39.1%) compared to the individuals with agenesis (26.2%).
      CONCLUSION: These data showed that the allele C could be associated with the
      third molar agenesis.

PMID- 19089166
TI  - Cleaning ability of chlorhexidine gel and sodium hypochlorite associated or not
      with EDTA as root canal irrigants: a scanning electron microscopy study.
AB  - The aim of this study was to evaluate the cleaning efficacy of 2% chlorhexidine
      gluconate gel (CHX) compared to 2.5% sodium hypochlorite solution (NaOCl)
      associated or not with 17% EDTA used as irrigants during the biomechanical
      preparation. Fifty freshly extracted single-rooted human teeth with complete apex
      formation were randomly divided into five groups: G1 - sterile saline, G2 - 2.5%
      NaOCl, G3 - 2% CHX, G4 - 2.5% NaOCl + EDTA and G5 - 2% CHX + EDTA. The specimens
      of G1 were subdivided into two control groups. The teeth were decoronated and the
      coronal and middle root thirds were prepared with Gates-Glidden burs, and the
      apical third was reserved to manual instrumentation. All procedures were
      performed by a single operator. In all groups, 2 mL of irrigant was delivered
      between each file change. The teeth were sectioned and prepared for analyses
      under scanning electron microscopy (SEM). SEM micrographs were graded according
      to a score scale by two examiners. Data were analyzed statistically by Kruskal
      Wallis and Dunn tests at 1% significance level. The best results were obtained in
      the groups in which the irrigant was used followed by the chelating agent. No
      statistically significant difference was observed among G4, G5 and the positive
      control group (p<0.01). The groups G2 and G3 were significantly different from
      the others, presenting the worst cleaning capacity. In conclusion, the use of the
      chelating agent is necessary to obtain clean canal walls, with open tubules and
      no heavy debris. The use of 2% chlorhexidine gluconate gel alone is not able to
      remove the smear layer.

PMID- 19089167
TI  - In vitro induction of enamel subsurface demineralization for evaluation of
      diagnostic imaging methods.
AB  - The aim of this study was to investigate a model of inducing enamel subsurface
      demineralization for evaluating diagnostic imaging methods. Fifty sound teeth had
      their crowns coated with acid-resistant varnish, leaving a 7 mm(2) circular
      window of exposed enamel in one of the proximal surfaces. The specimens were
      assigned to 5 groups (4 experimental and the control) and were kept immersed in a
      buffer solution at pH 4.8, 50% saturated in relation to enamel, for 60, 75, 90
      and 120 days, or were not exposed to the solution. Digital radiographs were
      taken, prior to and after each immersion period, and interpreted by a
      radiologist. For validation, the enamel was submitted to microhardness profiling.
      In addition, the solutions were analyzed for phosphorus (Pi) and calcium (Ca)
      concentrations. Microhardness data were evaluated using two-way ANOVA (p<0.05)
      and Tukey's test. Pi and Ca concentrations were compared using one-way ANOVA
      (alpha = 0.05). The performance of radiography was assessed by ROC analysis. The
      microhardness values for the control group ranged from 405 to 432 KHN. Of the 4
      experimental groups, the 60-day group demonstrated the highest values (179-379
      KHN) and the 120-day group, the lowest values (103-277 KHN). The lowest total
      concentrations of Pi and Ca (1.74 mM and 2.63 mM, respectively) were found in the
      solutions of the 60-day group, indicating the lowest rate of mineral loss,
      however, there was no significant difference among the other experimental groups.
      The performance for detecting images consistent with caries lesions was high (Az
      = 0.89). Therefore, this in vitro model of inducing demineralization may be
      considered suitable for research intended to evaluate imaging methods for the
      diagnosis of proximal caries lesions.

PMID- 19089168
TI  - All-ceramic and porcelain-fused-to-metal fixed partial dentures: a comparative
      study by 2D finite element analyses.
AB  - All-ceramic fixed partial dentures (FPDs) have an esthetic approach for oral
      rehabilitation. However, metal-ceramic FPDs are best indicated in the posterior
      area where the follow-up studies found a lower failure rate. This 2D finite
      element study compared the stress distribution on 3-unit all-ceramic and metal
      ceramic FPDs and identified the areas of major risk of failure. Three FPD models
      were designed: (1) metal-ceramic FPD; (2) All-ceramic FPD with the veneering
      porcelain on the occlusal and cervical surface of the abutment tooth; (3) All
      ceramic FPD with the veneering porcelain only on the occlusal surface. A 100 N
      load was applied in an area of 0.5 mm(2) on the working cusps, following these
      simulations: (1) on the abutment teeth and the pontic; (2) only on the abutment
      teeth; and (3) only on the pontic. Relative to the maximum stress values found
      for the physiological load, all-ceramic FPD with only occlusal veneering
      porcelain produced the lowest stress value (220 MPa), followed by all-ceramic FPD
      with cervical veneering porcelain (322 MPa) and metal-ceramic FPD (387 MPa). The
      stress distribution of the load applied on the abutments was significantly better
      compared to the other two load simulations. The highest principal stress values
      were low and limited in a small area for the three types of models under this
      load. When the load was applied on the pontic, the highest stress values appeared
      on the connector areas between the abutments and pontic. In conclusion, the best
      stress values and distribution were found for the all-ceramic FPD with the
      veneering porcelain only on the occlusal surface. However, in under clinical
      conditions, fatigue conditions and restoration defects must be considered.

PMID- 19089170
TI  - Shear bond strength of metallic brackets photo-activated with light-emitting
      diode (LED) at different exposure times.
AB  - The purpose of this study was to compare the shear bond strength of orthodontic
      metallic brackets photo-activated with two different light-curing sources at
      different exposure times: halogen light (XL 1500, 3M ESPE) and LED light
      (Ortholux, 3M Unitek). Sixty bovine permanent lower incisors were inserted into
      PVC tubes containing plaster. The buccal surfaces were cleaned with pumice and
      water, and then etched with 37% phosphoric acid gel. The XT Primer bonding agent
      (3M Unitek) was applied to the enamel surfaces and the metallic pre-coated
      brackets (Transbond APC II system, 3M Unitek) were attached to upper central
      incisors. The teeth were randomly divided into four groups (n=15). In Group I
      (Control), halogen light was used for 40 seconds, while in Groups II, III, and IV
      were light-cured with LED light unit for 40, 10, and 5 seconds, respectively. The
      teeth were stored in distilled water at 37 degrees C for 24 hours. The brackets
      were submitted to shear bond strength test in universal testing machine (Instron)
      at a crosshead speed of 0.5 mm/minute. Shear bond strength means (MPa) were 4.87
      for Group I; 5.89 for Group II; 4.83 for Group III, and 4.39 for Group IV.
      Tukey's test detected no statistically significant differences among the groups
      regarding the shear bond strength (p>0.05). Neither of the types of light-curing
      sources or exposure times influenced the shear bond strength of metallic
      brackets.

PMID- 19089169
TI  - Fluoride release of six restorative materials in water and pH-cycling solutions.
AB  - The fluoride release of restorative materials in deionized water has been the
      subject of many studies, but the behavior of these materials under conditions of
      acid challenge that simulates the oral cavity, needs to be further explored.
      Therefore, the aim of this study was to evaluate the fluoride release of
      restorative materials in two storage protocols: deionized water and pH-cycling
      system (demineralizing solution-pH 4.3 and remineralizing solution-pH 7.0) for 15
      days. Eight disks of each material (Vitremer-positive control, Dyract AP, Ariston
      pHc, Definite, TetricCeram and Z100-negative control) were prepared (11.0 mm x
      1.5 mm) and suspended individually in 4.0 mL of each solution, which were daily
      changed. Daily fluoride release was analyzed with an ion specific electrode
      (Orion 9609) by the direct method or after HMDS-facilitated diffusion, following
      1, 7 and 15 days. The values obtained were converted into microgF/mm(2) and the
      data analyzed by ANOVA and Tukey's test (p< 0.05). The results showed that all
      materials released more fluoride in the pH-cycling system, except for Ariston pHc
      which maintained a constant release during the experiment. The highest fluoride
      release was presented by the positive control, Vitremer in pH-cycling and by
      Ariston pHc, in deionized water. The negative control Z100 and the resins
      Definite and TetricCeram did not present statistically significant differences.

PMID- 19089171
TI  - Evaluation of surgical cavities filled with three types of calcium sulfate.
AB  - The aim of this study was to evaluate histologically, three types of calcium
      sulfate - Merck (Brazil), Surgiplaster (Italy) and Capset (USA) - in surgically
      created defects on rabbit femurs. Twenty male New Zealand rabbits were used. Two
      surgical bone defects (5 mm diameter x 8 mm depth) were created on each distal
      epiphysis using a #3 Dentoflex trephine bur. Defects were filled with: group 1 -
      di-hydrated calcium sulfate (Merck); group 2 - Capset (Lifecore-USA); group 3 -
      Surgiplaster (Classimport-Italy); group 4 - control (blood clot). The animals
      were sacrificed 30, 60, 90 and 180 days postoperatively. Semi-serial 6-mm-thick
      sections were obtained, stained with hematoxylin and eosin and examined under
      light microscopy. Bone defects treated with calcium sulfate exhibited new bone
      formation regardless of the product trademark.

PMID- 19089172
TI  - Effect of a propolis extract on Streptococcus mutans counts in vivo.
AB  - OBJECTIVE: To evaluate the antibacterial action of an extract of geopropolis
      produced by the bee Melipona compressipes fasciculata on the concentration of
      Streptococcus mutans colonizing the oral cavity of young patients. Forty-one
      young volunteers performed 21 mouth rinses divided into three rinses per day for
      7 days, with no other changes in their oral hygiene and dietary habits. Saliva
      was collected at three time points: before the first rinse, and one hour and 7
      days after the first rinse. A reduction in the concentration of S. mutans was
      observed in 49% of all samples collected after use of the extract, 26% showed no
      alterations, and an increasing in S. mutans was observed in 25%. Was performed
      with the Statistica for Windows 5.9 program using the Kruskal-Wallis test for
      analysis of variance and the Mann-Whitney U test, with the level of significance
      set at 5%. The propolis extract possesses in vivo antimicrobial activity against
      S. mutans present in the oral cavity and might be used as an alternative measure
      to prevent dental caries.

PMID- 19089173
TI  - Flexural strength of acrylic resins polymerized by different cycles.
AB  - Despite the large number of studies addressing the effect of microwave
      polymerization on the properties of acrylic resin, this method has received
      limited clinical acceptance. This study evaluated the influence of microwave
      polymerization on the flexural strength of a denture base resin. A conventional
      heat-polymerized (Classico), a microwave-polymerized (Onda-Cryl) and a
      autopolymerizing acrylic (Jet) resins were used. Five groups were established,
      according to polymerization cycles: A, B and C (Onda-Cryl, short cycle - 500W/3
      min, long - 90W/13 min + 500W/90 sec, and manufacturing microwave cycle - 320W/3
      min + 0W/3 min + 720W/3 min); T (Classico, water bath cycle - 74 degrees C/9h)
      and Q (Jet, press chamber cycle - 50 degrees C/15 min at 2 bar). Ten specimens
      (65 x 10 x 3.3mm) were prepared for each cycle. The flexural strength of the five
      groups was measured using a three-point bending test at a cross-head speed of 5
      mm/min. Flexural strength values were analyzed by one-way ANOVA and the Tukey's
      test was performed to identify the groups that were significantly different at 5%
      level. The microwave-polymerized groups showed the highest means (p<0.05) for
      flexural strength (MPa) (A = 106.97 +/- 5.31; B = 107.57 +/- 3.99; C = 109.63 +/-
      5.19), and there were no significant differences among them. The heat-polymerized
      group (T) showed the lowest flexural strength means (84.40 +/- 1.68), and differ
      significantly from all groups. The specimens of a microwavable denture base resin
      could be polymerized by different microwave cycles without risk of decreasing the
      flexural strength.

PMID- 19089174
TI  - Microbial leakage and apical inflammatory response in dog's teeth after root
      canal filling with different sealers, post space preparation and exposure to the
      oral environment.
AB  - Coronal leakage is an important factor affecting the outcome of endodontic
      therapy. This study evaluated the microbial leakage (ML) and the apical
      inflammatory response (AIR) in dog's teeth after root canal filling with three
      endodontic sealers, post preparation and exposure to the oral environment,
      testing the hypothesis that there is a positive correlation between these two
      histological parameters (ML and AIR). Sixty-four root canals of 8 mongrel dogs
      were cleaned, shaped and randomly distributed into groups according to the sealer
      to be used: Sealer 26 (n=18); AH Plus (n=18); RoekoSeal (n=19); no sealer -
      control group (n=9). Root canals were filled by the lateral condensation
      technique. Post space preparation left 4 mm of filling material in the apical
      root third, and specimens were exposed to the oral environment for 90 days. The
      dogs were killed and jaw blocks were histologically processed using Brown & Brenn
      and HE staining techniques. ML and AIR were scored from 1 to 4. Results were
      analyzed statistically using ANOVA, Duncan's post-hoc test and Spearman's
      correlation. ML and AIR score means were: Sealer 26 - 2.44+/-0.98 and 2.50+/
      0.70; AH Plus - 2.50+/-0.78 and 2.22+/-0.54; RoekoSeal - 1.84+/-0.95 and 2.63+/
      0.83; Control - 2.56+/-1.23 and 3.11+/-0.60. Statistically significant
      differences in AIR scores were found between the AH Plus and control groups
      (p<0.05). Although RoekoSeal had the lowest ML means, and AH Plus, the lowest AIR
      means after 90-day exposure to the oral environment, no statistically significant
      differences were found between the three sealers under study, and no correlation
      was found between ML and AIR.

PMID- 19089175
TI  - Criteria adopted by dentists to indicate the extraction of periodontally involved
      teeth.
AB  - When dealing with patients with periodontal disease of variable severities,
      dentists must often choose between treating and restoring the involved tooth or
      indicating its extraction. Different criteria have been adopted in this decision
      making process. The purpose of this study was to evaluate the criteria adopted by
      dentists to indicate the extraction of teeth with periodontitis. Dentists were
      interviewed at their private practices in three cities of the state of Rio Grande
      do Sul, Brazil. The evaluated criteria included severity of attachment loss,
      tooth mobility, furcation involvement, prosthetic planning, periodontal
      endodontic lesion, possible systemic involvement due to the presence of
      periodontitis, referral to a periodontist for evaluation, radiographic bone loss
      greater than 50%, presence of extensive caries, socio-economic and cultural
      status of the patient, among others. The most often adopted criteria to indicate
      the extraction of periodontally affected teeth were the presence of mobility
      (37.5%), severity of attachment loss (24.3%) and radiographic bone loss greater
      than 50% (21.2%). The results of the present study demonstrated the difficulties
      faced by dentists to indicate the extraction of teeth with severe attachment
      loss, in addition to the establishment of an adequate prognosis. Aspects
      associated with the past disease were still the most often reported to indicate
      the extraction of teeth for periodontal reasons.

PMID- 19089176
TI  - Characterization of bone cells obtained from the calvaria of neonatal rats (osteo
      1) after serial subculture.
AB  - The objective of the present study was to characterize bone cells grown in two
      culture media, and to determine the effective concentration of OP-1 on the growth
      of osteo-1 cells. Subcultured rat bone cells (osteo-1) were grown in alpha
      modified Eagle's minimal essential medium (alpha-MEM) and Dulbecco's modified
      Eagle's medium (DMEM) and total protein content, alkaline phosphatase activity
      and the formation of mineralized nodules were evaluated after 7, 14 and 21 days.
      Cells were exposed to different concentrations of rhOP-1 for 1, 3, 5 and 7 days
      and compared with an untreated control. Osteo-1 cells presented a significant
      increase in alkaline phosphatase activity and calcium deposits were observed at
      21 days. Cells treated with 10 and 20 ng/mL rhOP-1 for 24 h showed a significant
      increase in cell viability when compared to control. Osteo-1 cells cultured on
      DMEM demonstrated an osteoblastic phenotype as indicated by high alkaline
      phosphatase activity and the presence of calcified nodules. The results suggest
      that low concentrations of OP-1 may promote an osteogenic effect on osteo-1
      cells.

PMID- 19089177
TI  - Volumetric polymerization shrinkage of contemporary composite resins.
AB  - The polymerization shrinkage of composite resins may affect negatively the
      clinical outcome of the restoration. Extensive research has been carried out to
      develop new formulations of composite resins in order to provide good handling
      characteristics and some dimensional stability during polymerization. The purpose
      of this study was to analyze, in vitro, the magnitude of the volumetric
      polymerization shrinkage of 7 contemporary composite resins (Definite, Suprafill,
      SureFil, Filtek Z250, Fill Magic, Alert, and Solitaire) to determine whether
      there are differences among these materials. The tests were conducted with
      precision of 0.1 mg. The volumetric shrinkage was measured by hydrostatic
      weighing before and after polymerization and calculated by known mathematical
      equations. One-way ANOVA (a = 0.05) was used to determine statistically
      significant differences in volumetric shrinkage among the tested composite
      resins. Suprafill (1.87+/-0.01) and Definite (1.89+/-0.01) shrank significantly
      less than the other composite resins. SureFil (2.01+/-0.06), Filtek Z250 (1.99+/
      0.03), and Fill Magic (2.02+/-0.02) presented intermediate levels of
      polymerization shrinkage. Alert and Solitaire presented the highest degree of
      polymerization shrinkage. Knowing the polymerization shrinkage rates of the
      commercially available composite resins, the dentist would be able to choose
      between using composite resins with lower polymerization shrinkage rates or
      adopting technical or operational procedures to minimize the adverse effects
      deriving from resin contraction during light-activation.

PMID- 19089178
TI  - Antimicrobial effect of intracanal substances.
AB  - In some situations, endodontic infections do not respond to therapeutic protocol.
      In these cases, it is suggested the administration of an alternative intracanal
      medication that presents a wide spectrum of action and has an in-depth effect on
      the root canal system. The purpose of this study was to assess the antimicrobial
      action of ciprofloxacin, metronidazole and polyethylene glycol and natrosol
      vehicles with different associations and concentrations. The minimum inhibitory
      concentration (MIC) was determined by using the agar dilution method. The culture
      media (Muller-Hinton agar) were prepared containing antimicrobial agents at
      multiple two-fold dilutions of 0.25 to 16 microg/mL, and with the vehicles at the
      concentrations of 50, 45, 40, 35, 30 and 25%. Twenty-three microbial strains were
      selected for the study. Metronidazole was not capable of eliminating any of the
      tested microorganisms. The association of ciprofloxacin with metronidazole
      resulted in a reduction of the MIC. The vehicle polyethylene glycol inhibited the
      growth of 100% of the tested strains, while natrosol inhibited 18% of the
      strains. Ciprofloxacin formulations with polyethylene glycol presented better
      effects than those of formulations to which metronidazole was added. It was
      possible to conclude that ciprofloxacin presented antimicrobial action against
      all tested bacterial strains, and its association with metronidazole was
      synergic. The vehicle polyethylene glycol showed antimicrobial effect and the
      ciprofloxacin/polyethylene glycol association was the most effective combination
      for reducing the tested bacteria and yeasts.

PMID- 19089179
TI  - Bond strength of resin modified glass ionomer cement to primary dentin after
      cutting with different bur types and dentin conditioning.
AB  - The aim of this in vitro study was to evaluate the effect of different bur types
      and acid etching protocols on the shear bond strength (SBS) of a resin modified
      glass ionomer cement (RM-GIC) to primary dentin. Forty-eight clinically sound
      human primary molars were selected and randomly assigned to four groups (n=12).
      In G1, the lingual surface of the teeth was cut with a carbide bur until a 2.0-mm
      diameter dentin area was exposed, followed by the application of RM-GIC (Vitremer
      - 3M/ESPE) prepared according to the manufacturer's instructions. The specimens
      of G2, received the same treatment of G1, however the dentin was conditioned with
      phosphoric acid. In groups G3 and G4 the same procedures of G1 and G2 were
      conducted respectively, nevertheless dentin cutting was made with a diamond bur.
      The specimens were stored in distilled water at 37 degrees C for 24h, and then
      tested in a universal testing machine. SBS data were submitted to 2-way ANOVA (=
      5%) and indicated that SBS values of RM-GIC bonded to primary dentin cut with
      different burs were not statistically different, but the specimens that were
      conditioned with phosphoric acid presented SBS values significantly higher that
      those without conditioning. To observe micromorphologic characteristics of the
      effects of dentin surface cut by diamond or carbide rotary instruments and
      conditioners treatment, some specimens were examined by scanning electron
      microscopy. Smear layer was present in all specimens regardless of the type of
      rotary instrument used for dentin cutting, and specimens etched with phosphoric
      acid presented more effective removal of smear layer. It was concluded that SBS
      of a RM-GIC to primary dentin was affected by the acid conditioning but the bur
      type had no influence.

PMID- 19089180
TI  - The perfect time to say "thank you".

PMID- 19089181
TI  - Regional odontodysplasia: case report.
AB  - Regional odontodysplasia (RO) is a rare developmental anomaly involving both
      mesodermal and ectodermal dental components in a group of contiguous teeth. It
      affects the primary and permanent dentitions in the maxilla and mandible or both
      jaws. Generally it is localized in only one arch. The etiology of this dental
      anomaly is uncertain. Clinically, affected teeth have an abnormal morphology, are
      soft on probing and typically discolored, yellow or yellowish-brown.
      Radiographically, the affected teeth show a "ghostlike" appearance. This paper
      reports the case of a 5-year-old girl presenting this rare anomaly on the left
      side of the maxillary arch, which crossed the midline. The primary maxillary left
      teeth (except for the canine) and the primary maxillary right central incisor
      were missing due to previous extractions. The permanent teeth had a "ghostlike"
      appearance radiographically. The treatment performed was rehabilitation with
      temporary partial acrylic denture and periodic controls. In the future, the
      extraction of affected permanent teeth and rehabilitation with dental implants
      will be evaluated. The presentation of this case adds valuable information to
      pediatric dentists to review special clinical and radiographic features of RO,
      which will facilitate the diagnosis and treatment of patients with this
      condition.

PMID- 19089182
TI  - The effect of different light-curing units on tensile strength and microhardness
      of a composite resin.
AB  - The aim of this study was to evaluate the influence of different light-curing
      units on the tensile bond strength and microhardness of a composite resin (Filtek
      Z250 - 3M/ESPE). Conventional halogen (Curing Light 2500 - 3M/ESPE; CL) and two
      blue light emitting diode curing units (Ultraled - Dabi/Atlante; UL; Ultrablue IS
      - DMC; UB3 and UB6) were selected for this study. Different light intensities
      (670, 130, 300, and 600 mW/cm(2), respectively) and different curing times (20s,
      40s and 60s) were evaluated. Knoop microhardness test was performed in the area
      corresponding to the fractured region of the specimen. A total of 12 groups
      (n=10) were established and the specimens were prepared using a stainless steel
      mold composed by two similar parts that contained a cone-shaped hole with two
      diameters (8.0 mm and 5.0 mm) and thickness of 1.0 mm. Next, the specimens were
      loaded in tensile strength until fracture in a universal testing machine at a
      crosshead speed of 0.5 mm/min and a 50 kg load cell. For the microhardness test,
      the same matrix was used to fabricate the specimens (12 groups; n=5).
      Microhardness was determined on the surfaces that were not exposed to the light
      source, using a Shimadzu HMV-2 Microhardness Tester at a static load of 50 g for
      30 seconds. Data were analyzed statistically by two-way ANOVA and Tukey's test
      (p<0.05). Regarding the individual performance of the light-curing units, there
      was similarity in tensile strength with 20-s and 40-s exposure times and higher
      tensile strength when a 60-s light-activation time was used. Regarding
      microhardness, the halogen lamp had higher results when compared to the LED
      units. For all light-curing units, the variation of light-exposure time did not
      affect composite microhardness. However, lower irradiances needed longer light
      activation times to produce similar effect as that obtained with high-irradiance
      light-curing sources.

PMID- 19089183
TI  - Long-term bond strength of adhesive systems applied to etched and deproteinized
      dentin.
AB  - The aim of this study was to evaluate the early and 12-month bond strength of two
      adhesive systems (Single Bond-SB and One Step-OS) applied to demineralized dentin
      (WH) and demineralized/NaOCl-treated dentin (H). Twenty flat dentin surfaces were
      exposed, etched, rinsed and slightly dried. For the H groups, a solution of 10%
      NaOCl was applied for 60 s, rinsed (15 s) and slightly dried. The adhesives were
      applied according to the manufacturer's instructions and composite resin crowns
      were incrementally constructed. After 24 h (water-37 degrees C), the specimens
      was sectioned in order to obtain resin-dentin sticks (0.8 mm(2)). The specimens
      were tested in microtensile (0.5 mm/min) immediately (IM) or after 12 months of
      water storage (12M). The data (MPa) were subjected to ANOVA and Tukey's test
      (a=0.05). Only the main factors adhesive and time were significant (p=0.004 and
      p=0.003, respectively). SB (42.3+/-9.1) showed higher bond strengths than OS
      (33.6+/-11.6). The mean bond strength for IM-group (42.5+/-8.7) was statistically
      superior to 12M (33.3+/-11.8). The use of 10% NaOCl, after acid etching, did not
      improve the immediate and the long-term resin-dentin bond strength.

PMID- 19089184
TI  - A new approach for interexaminer reliability data analysis on dental caries
      calibration.
AB  - OBJECTIVES: a) to evaluate the interexaminer reliability in caries detection
      considering different diagnostic thresholds and b) to indicate, by using Kappa
      statistics, the best way of measuring interexaminer agreement during the
      calibration process in dental caries surveys. METHODS: Eleven dentists
      participated in the initial training, which was divided into theoretical
      discussions and practical activities, and calibration exercises, performed at
      baseline, 3 and 6 months after the initial training. For the examinations of 6-7
      year-old schoolchildren, the World Health Organization (WHO) recommendations were
      followed and different diagnostic thresholds were used: WHO
      (decayed/missing/filled teeth - DMFT index) and WHO + IL (initial lesion)
      diagnostic thresholds. The interexaminer reliability was calculated by Kappa
      statistics, according to WHO and WHO+IL thresholds considering: a) the entire
      dentition; b) upper/lower jaws; c) sextants; d) each tooth individually. RESULTS:
      Interexaminer reliability was high for both diagnostic thresholds; nevertheless,
      it decreased in all calibration sections when considering teeth individually.
      CONCLUSION: The interexaminer reliability was possible during the period of 6
      months, under both caries diagnosis thresholds. However, great disagreement was
      observed for posterior teeth, especially using the WHO+IL criteria. Analysis
      considering dental elements individually was the best way of detecting
      interexaminer disagreement during the calibration sections.

PMID- 19089185
TI  - Influence of the distance of the curing light source and composite shade on
      hardness of two composites.
AB  - This study evaluated the influence of curing tip distance, shade and filler
      particle size on Vickers microhardness (VHN) of composite resins. Two composites
      were tested: Filtek Z250 microhybrid (3M ESPE; shades A1 and A3.5) and Filtek
      Supreme nanofilled (3M ESPE; shades A1B and A3.5B). For each resin, 42 specimens
      (5 mm in diameter and 2 mm height) were prepared being 21 for each shade. The
      specimens were exposed using a 20-second exposure to a quartz-tungsten-halogen
      light source with an irradiance of approximately 560 mW/cm(2), at the following
      distances: 0 mm (surface contact), 6 mm and 12 mm from composite surface.
      Effectiveness of cure of different resins, shades and curing distances was
      determined by measuring the top and bottom hardness (VHN) of specimens using a
      digital microhardness tester (load: 50 g; dwell time: 45 seconds) 24 hours
      following curing. The hardness ratio was calculated by dividing VHN of the bottom
      surface by VHN of top surface. Three-way ANOVA and Tukey's post-hoc test (p<0.05)
      revealed statistically significant differences for all analyzed factors. As for
      top hardness, as microhardness ratio (bottom/top), the factors shade, distance
      and composite filler particle size exerted influence on resin curing. Lighter
      shade composites (A1 and A1B) showed higher hardness values. At 6 and 12 mm
      curing tip distances, hardness was lower when compared to 0 mm. The microhybrid
      composite resin presented higher hardness, being its microhardness ratio
      satisfactory only at 0 mm for both shades and at 6 mm for the lighter shade. The
      nanofilled composite resin did not present satisfactory microhardness at the
      bottom while the microhybrid composite resin had higher hardness than the
      nanofilled. Composite's curing tip distance and shade can influence hardness.

PMID- 19089186
TI  - Comparison between inverted and unprocessed digitized radiographic imaging in
      periodontal bone loss measurements.
AB  - The advances in digital imaging technology in dentistry have provided an
      alternative to film-based radiography and have given new options to detect
      periodontal bone loss. The purpose of this study was to compare inverted and
      unprocessed digitized radiographic imaging in periodontal bone loss measurements.
      Thirty-five film-based periapical radiographs of patients suffering from moderate
      to advanced untreated periodontal bone loss associated to lower premolar and
      molars was selected from the department files, with 40 bone loss areas. The film
      based radiographs were digitized with a flatbed scanner with a transparency and
      radiograph adapter used for transilluminating the radiograph imaging.
      Digitization was performed at 600 dpi and in gray scale. The images were
      digitized using Image Tool software by applying image inversion, that is,
      transformation of radiopaque structures into radiolucent structures and vice
      versa. The digital data were saved as JPEG files. The images were displayed on a
      15-inch and 24-bit video monitor under reduced room lighting. One calibrated
      examiner performed all radiographic measurements, three times, from the
      cementoenamel junction to the most apical extension of the bone loss, in both
      types of image (inverted and unprocessed). Brightness and contrast were adjusted
      according to the examiner's individual demand. Intraclass correlation coefficient
      was used to compare the measurements from both types of images. The means of
      radiographic measurements, in mm, for inverted and unprocessed digitized imaging
      were 6.4485 and 6.3790, respectively. The intraclass correlation coefficient was
      significant (0.99) The inverted and unprocessed digitized radiographic images
      were reliable and there was no difference in the diagnostic accuracy between
      these images regarding periodontal bone loss measurements.

PMID- 19089187
TI  - Transmission of composite polymerization contraction force through a flowable
      composite and a resin-modified glass ionomer cement.
AB  - The purpose of this study was to evaluate the individual contraction force during
      polymerization of a composite resin (Z-250), a flowable composite (Filtek Flow,
      FF) and a resin-modified glass ionomer cement (Vitrebond, VB), and the
      transmission of Z-250 composite resin polymerization contraction force through
      different thicknesses of FF and VB. The experiment setup consisted of two
      identical parallel steel plates connected to a universal testing machine. One was
      fixed to a transversal base and the other to the equipment's cross head. The
      evaluated materials were inserted into a 1-mm space between the steel plates or
      between the inferior steel plate and a previously polymerized layer of an
      intermediate material (either FF or VB) adhered to the upper steel plate. The
      composite resin was light-cured with a halogen lamp with light intensity of 500
      mW/cm(2) for 60 s. A force/time graph was obtained for each sample for up to 120
      s. Seven groups of 10 specimens each were evaluated: G1: Z-250; G2: FF; G3: VB;
      G4: Z-250 through a 0.5-mm layer of FF; G5: Z-250 through a 1-mm layer of FF; G6:
      Z-250 through a 0.5-mm of VB; G7: Z-250 through a 1-mm layer of VB. They were
      averaged and compared using one-way ANOVA and Tukey test at a = 0.05. The
      obtained contraction forces were: G1: 6.3N + 0.2N; G2: 9.8 + 0.2N; G3: 1.8 +
      0.2N; G4: 6.8N + 0.2N; G5: 6.9N + 0.3N; G6: 4.0N + 0.4N and G7: 2.8N + 0.4N. The
      use of VB as an intermediate layer promoted a significant decrease in
      polymerization contraction force values of the restorative system, regardless of
      material thickness. The use of FF as an intermediate layer promoted an increase
      in polymerization contraction force values with both material thicknesses.

PMID- 19089188
TI  - Bond strength of resin-resin interfaces contaminated with saliva and submitted to
      different surface treatments.
AB  - The purpose of this study was to investigate the effect of different surface
      treatments on shear bond strength of saliva-contaminated resin-resin interfaces.
      Flat resin surfaces were fabricated. In the control group, no contamination or
      surface treatment was performed. The resin surfaces of the experimental groups
      were contaminated with saliva and air-dried, and then submitted to: (G1) rinsing
      with water and drying; (G2) application of an adhesive system; (G3) rinsing and
      drying, abrasion with finishing disks, etching and application of adhesive
      system; (G4) rinsing and drying, etching, application of silane and adhesive
      system. Resin cylinders were placed over the treated surfaces. The specimens were
      stored in water or ethanol. Shear bond strength tests were performed and the mode
      of failure was evaluated. Data were submitted to two-way ANOVA and Dunnett T3
      test. Contamination of resin-resin interfaces with saliva significantly reduced
      shear strength, especially after prolonged storage (p<0.05). Similar values to
      the original bond strength were obtained after abrasion and application of
      adhesive (G3) or etching and application of silane and adhesive (G4). If
      contamination occurs, a surface treatment is required to guarantee an adequate
      interaction between the resin increments.

PMID- 19089189
TI  - Effect of a post-polymerization treatments on the flexural strength and Vickers
      hardness of reline and acrylic denture base resins.
AB  - This study evaluated the effect of water-bath and microwave post-polymerization
      treatments on the flexural strength and Vickers hardness of four autopolymerizing
      reline resins (Duraliner II-D, Kooliner-K, Tokuso Rebase Fast-TR and Ufi Gel Hard
      C-UGH) and one heat-polymerized acrylic resin (Lucitone 550-L), processed using
      two polymerization cycles (short cycle - 90 minutes at 73 degrees C and 100
      degrees C for 30 minutes; and long cycle - 9 hours at 71 degrees C). For each
      material, thirty specimens (64 x 10 x 3.3 mm) were made and divided into 3 groups
      (n=10). Specimens were tested after: processing (control group); water-bath at 55
      degrees C for 10 minutes (reline materials) or 60 minutes (L); and microwave
      irradiation. Flexural strength tests were performed at a crosshead speed of 5
      mm/min using a three-point bending device with a span of 50 mm. The flexural
      strengths values were calculated in MPa. One fragment of each specimen was
      submitted to Vickers hardness test. Data were analyzed by 2-way ANOVA followed by
      Tukey's HSD test (alpha=0.05). L microwaved specimens (short cycle) exhibited
      significantly higher flexural strength means than its respective control group
      (p<0.05). Water-bath promoted a significant increase (p<0.05) in flexural
      strength of K and L (long cycle). The hardness of the tested materials was not
      influenced by the post-polymerization treatments. Post-polymerization treatments
      could be used to improve the flexural strength of some materials tested.

PMID- 19089190
TI  - Evaluation of clinical periodontal conditions in smokers and non-smokers.
AB  - Given that tobacco smoking habit is a risk factor for periodontal diseases, the
      aim of this study was to compare clinical periodontal aspects between smokers and
      non-smokers. The clinical status were assessed in 55 patients, 29 smokers and 26
      non-smokers, aged 30 to 50 years, with mean age of 40. The clinical parameters
      used were: probing depth (PD), plaque index (PI), gingival index (GI), clinical
      attachment level (CAL), gingival recession (GR) and gingival bleeding index (GBI)
      for arches (upper and lower) and teeth (anterior and posterior). Tooth loss was
      also evaluated in both groups. Multiple regression analysis showed: tendency of
      greater probing depth and clinical attachment level means for smokers; greater
      amount of plaque in smokers in all regions; greater gingival index means for non
      smokers with clinical significance (p<0.05) in all regions. Although, without
      statistical significance, the analysis showed greater gingival bleeding index
      means almost always for non-smokers; similar gingival recession means in both
      groups and tendency of upper tooth loss in smokers and lower tooth loss in non
      smokers. The findings of this study showed that clinical periodontal parameters
      may be different in smokers when compared to non-smokers and that masking of some
      periodontal signs can be a result of nicotine's vasoconstrictor effect.

PMID- 19089191
TI  - Prenatal and neonatal variables associated with enamel hypoplasia in deciduous
      teeth in low birth weight preterm infants.
AB  - This study investigated possible prenatal and neonatal variables that may
      influence the prevalence of tooth enamel hypoplasia in preterm and low birth
      weight children (LBW) and a matched control group of term children with normal
      birth weight (NBW). The study sample consisted of 61 children born preterm and
      with LBW examined at 18-34 months of age. The control group was formed by 61
      infants born full term and with NBW examined at 31-35 months of age. All children
      were born at the Center of Integrated Attention of Women's Health (CAISM
      UNICAMP). FDI criteria were followed for dental examination. Medical data was
      collected retrospectively from hospital records. Among preterms, 57.4% had some
      type of developmental defects of enamel (DDE), 52.5 % had opacities and 21.3 %
      presented hypoplasia. Among full-term children, 24.6% presented DDE, 24.6% had
      opacities and 3.3% had hypoplasia. LBW preterm infants presented a higher
      prevalence of hypoplasia than NBW controls. The deciduous teeth most affected by
      hypoplasia were maxillary incisors. There was no significant association with
      prenatal variables; among neonatal variables there was a significant association
      with respiratory distress syndrome and neurological examination at discharge with
      an altered result.

PMID- 19089192
TI  - Radiographic study of dental anomalies in Brazilian patients with
      neuropsychomotor disorders.
AB  - The purposes of this study were to investigate radiographically the dental and
      maxillomandibular in patients with neuropsychomotor disorders and determine the
      role of panoramic radiographs for quantitative and qualitative analyses of dental
      alterations. A total of 322 panoramic radiographs from 190 males and 132 females
      aged 4 to 57 years were obtained from the files of the Center for Care to
      Patients with Special Needs (CAPE; Dental School, University of Sao Paulo) and
      subdivided into syndromes, special needs, neurological, neuromuscular or cerebral
      disorders, and sequels of diseases. 32% of dental alterations were in tooth
      position, with 69% of this group associated with tooth rotation. The mandible
      accounted for 54.62% of alterations. The male gender (55.85%) and the permanent
      dentition (78.7%) were most affected. Panoramic radiographs were proved to be
      well suited for quantitative evaluation of dental anomalies of epidemiological
      nature. Panoramic radiographs are important diagnostic resources when applied to
      patients with special needs because of the difficulty to place intraoral films
      and held them correctly positioned during the radiographic technique.

PMID- 19089193
TI  - Elastomeric impression as a diagnostic method of cavitation in proximal dentin
      caries in primary molars.
AB  - The purpose of this study was to validate the elastomeric impression after
      temporary tooth separation as a method of cavitation detection in proximal caries
      lesions in primary molars with outer half dentin radiolucency. Fifty-one children
      (4-10 years old), presenting radiolucency in the outer half of the dentin at the
      proximal surfaces of primary molars and proximal anatomic contact with the
      adjacent tooth (without restoration/cavitated caries lesion) were enrolled in the
      study. Temporary tooth separation was performed with an orthodontic rubber ring
      placed around the contact point during 2-3 days. Thereafter, impression of the
      proximal surfaces was made. The elastomeric impressions were classified as "non
      cavitated" or "cavitated" surfaces. Visual inspection after tooth separation was
      considered as the gold standard. Examiner reliability of visual inspection after
      tooth separation was determined (kappa 0.92). Impression examination was repeated
      every 5 participants to evaluate the reproducibility of the method. The frequency
      of cavitated lesions was 65%, and 67% of those were inactive. Sensitivity,
      specificity, positive and negative predictive values were 0.88% (95%CI 0.73
      0.95), 0.89% (95%CI 0.67-0.97), 0.94% (95%CI 0.79-0.98) and 0.80% (95%CI 0.58
      0.92), respectively. Impression examination showed total agreement regarding
      cavitation. The evaluation of elastomeric impression after tooth separation is a
      useful clinical resource in cavitation detection for clinicians and researchers
      when visual inspection is doubtful.

PMID- 19089194
TI  - Avulsion of permanent teeth: analysis of the efficacy of na informative campaign
      for professionals from elementary schools.
AB  - Tooth avulsion is a very common event in children and emergency care procedures
      are crucial for case prognosis. As anyone at the moment of accident can provide
      first-aid measures, knowledge of school professionals dealing with children is of
      paramount importance. An informative campaign about dental trauma was performed
      in urban schools in the city of Adamantina, Sao Paulo state, Brazil, in an
      attempt to educate school professionals about emergency procedures in cases of
      tooth avulsion. A questionnaire arguing on personal information, tooth avulsion
      knowledge and personal impressions of the campaign was handed out for evaluation
      of the informative campaign. Eighty school professionals participated in the
      survey. Most participants were females (93.75%) aged 41-60 years old (53.75%)
      with a college degree (77.5%). Time at work ranged from 1-5 years (22.5%). The
      efficacy of the campaign was considered positive, as 100% of the interviewees
      replied to the importance of emergency procedures in case of tooth avulsion. In
      addition, 81.25% of the respondents answered that they would store the avulsed
      tooth in some storage medium, of which milk was the most frequently mentioned
      (84.61%). The participants considered the campaign as satisfactory and a region
      wide campaign will be accomplished at other schools.

PMID- 19089195
TI  - Susceptibility of strict and facultative anaerobes Isolated from endodontic
      infections to metronidazole and beta-lactams.
AB  - Endodontic infections are mixed aerobic-anaerobic infections and several
      microbial groups associated to these pathologies are also involved in orofacial
      infections. The goal of this study was to evaluate the susceptibility of
      microorganisms isolated from endodontic infections to beta-lactams and
      metronidazole and verify the production of beta-lactamases. Clinical specimens
      were collected from 58 endodontic infections of 52 patients. The microorganisms
      were isolated in selective and non-selective culture media, under anaerobiosis
      and aerobiosis, and identified using biochemical methods. In the susceptibility
      tests, it was used an agar dilution method, and Wilkins-Chalgren agar enriched
      with blood, hemin and menadione for the anaerobes, while Mueller-Hinton agar was
      employed for the facultative anaerobes. The production of beta-lactamases was
      evaluated through the biological and chromogenic cephalosporin methods. All
      tested isolates were sensitive to imipenem and 99.3% to amoxicillin/clavulanate
      association, while 16.1% showed resistance to amoxicillin and penicillin G, and
      4.89% to cefoxitin. Resistance to metronidazole was just found in facultative
      anaerobes. Production of beta-lactamases was detected in 18.2% of the isolates
      and presented a correlation with resistance to beta-lactams.

PMID- 19089198
TI  - Intrapupal temperature variation during Er,Cr: YSGG enamel irradiation on carries
      prevention.
AB  - Studies have shown the cariostatic effect of Er,Cr:YSGG (2.78 mm) laser
      irradiation on human enamel and have suggested its use on caries prevention.
      However there are still no reports on the intrapulpal temperature increase during
      enamel irradiation using parameters for caries prevention. The aim of this in
      vitro study was to evaluate the temperature variation in the pulp chamber during
      human enamel irradiation with Er,Cr:YSGG laser at different energy densities.
      Fifteen enamel blocks obtained from third molars (3 x 3 x 3 mm) were randomly
      assigned to 3 groups (n=5): G1--Er,Cr:YSGG laser 0.25 W, 20 Hz, 2.84 J/cm(2), G2-
      Er,Cr:YSGG laser 0.50 W, 20 Hz, 5.68 J/cm(2), G3--Er,Cr:YSGG laser 0.75 W, 20 Hz,
      8.52 J/cm(2). During enamel irradiation, two thermocouples were fixed in the
      inner surface of the specimens and a thermal conducting paste was used. One-way
      ANOVA did not show statistically significant difference among the experimental
      groups (alpha=0.05). There was intrapulpal temperature variation < or = 0.1
      degrees C for all irradiation parameters. In conclusion, under the tested
      conditions, the use of Er,Cr:YSGG laser with parameters set for caries prevention
      lead to an acceptable temperature increase in the pulp chamber.

PMID- 19089197
TI  - Development of Candida-associated denture stomatitis: new insights.
AB  - Despite therapeutic progress, opportunistic oral fungal infectious diseases have
      increased in prevalence, especially in denture wearers. The combination of
      entrapment of yeast cells in irregularities in denture-base and denture-relining
      materials, poor oral hygiene and several systemic factors is the most probable
      cause for the onset of this infectious disease. Hence colonization and growth on
      prostheses by Candida species are of clinical importance. The purpose of this
      review is to critically discuss several key factors controlling the adhesion of
      Candida species which are relevant to denture-associated stomatitis. Although
      there is some consensus on the role of surface properties, studies on several
      other factors, as the use of denture liners, salivary properties and yeast
      bacterial interactions, have shown contradictory findings. A comprehensive
      fundamental understanding is hampered by conflicting findings due to the large
      variations in experimental protocols, while other factors have never been
      thoroughly studied. Surface free energy and surface roughness control the initial
      adherence, but temporal changes have not been reported. Neither have in vivo
      studies shown if the substratum type is critical in dictating biofilm
      accumulation during longer periods in the oral environment. The contribution of
      saliva is unclear due to factors like variations in its collection and handling.
      Initial findings have disclosed that also bacteria are crucial for the successful
      establishment of Candida in biofilms, but the clinical significance of this
      observation is yet to be confirmed. In conclusion, there is a need to standardize
      experimental procedures, to bridge the gap between laboratory and in vivo
      methodologies and findings and--in general--to thoroughly investigate the factors
      that modulate the initial attachment and subsequent colonization of denture-base
      materials and the oral mucosa of patients subjected to Candida infections.
      Information on how these factors can be controlled is required and this may help
      to prevent the disease. The societal impact of such information is significant
      given the magnitude of the candidosis problem worldwide.

PMID- 19089199
TI  - Comparative scanning electron microscopic study of the effect of different dental
      conditioners on dentin micromorphology.
AB  - This study evaluated comparatively by scanning electron microscopy (SEM) the
      effect of different dental conditioners on dentin micromorphology, when used
      according to the same protocol. Forty dentin sticks were obtained from 20 caries
      free third human molars and were assigned to 4 groups corresponding to 3
      conditioners (phosphoric acid 37%, Clearfil SE Bond and iBond) and an untreated
      control group. After application of the conditioners, the specimens were immersed
      in 50% ethanol solution during 10 s, chemically fixed and dehydrated to prepare
      them to SEM analysis. In the control group, dentin surface was completely covered
      by smear layer and all dentinal tubules were occluded. In the phosphoric acid
      etched group, dentin surface was completely clean and presented exposed dentinal
      tubule openings; this was the only group in which the tubules exhibited the
      funnel-shaped aspect. In the groups conditioned with Clearfil SE Bond primer and
      iBond, which are less acidic than phosphoric acid, tubule openings were occluded
      or partially occluded, though smear layer removal was observed. SE Bond was more
      efficient in removing the smear layer than iBond. In the Clearfil SE Bond group,
      the cuff-like aspect of peritubular dentin was more evident. It may be concluded
      all tested conditioners were able to change dentin morphology. However, it cannot
      be stated that the agent aggressiveness was the only cause of the
      micromorphological alterations because a single morphological pattern was not
      established for each group, but rather an association of different aspects,
      according to the aggressiveness of the tested conditioner.

PMID- 19089200
TI  - Influence of thermal stress on marginal integrity of restorative materials.
AB  - The aim of this study was to evaluate the influence of thermal stress on the
      marginal integrity of restorative materials with different adhesive and thermal
      properties. Three hundred and sixty Class V cavities were prepared in buccal and
      lingual surfaces of 180 bovine incisors. Cervical and incisal walls were located
      in dentin and enamel, respectively. Specimens were restored with resin composite
      (RC); glass ionomer (GI) or amalgam (AM), and randomly assigned to 18 groups
      (n=20) according to the material, number of cycles (500 or 1,000 cycles) and
      dwell time (30 s or 60 s). Dry and wet specimens served as controls Specimens
      were immersed in 1% basic fuchsine solution (24 h), sectioned, and microleakage
      was evaluated under x40 magnification. Data were analyzed by Kruskal-Wallis and
      Mann-Whitney tests: thermal cycling regimens increased leakage in all AM
      restorations (p<0.05) and its effect on RC and GI restorations was only
      significant when a 60-s dwell time was used (p<0.05). Marginal integrity was more
      affected in AM restorations under thermal cycling stress, whereas RC and GI
      ionomer restoration margins were only significantly affected only under longer
      dwell times.

PMID- 19089201
TI  - Influence of different cantilever extensions and glass or polyaramide
      reinforcement fibers on fracture strength of implant-supported temporary.
AB  - In long-term oral rehabilitation treatments, resistance of provisional crowns is
      a very important factor, especially in cases of an extensive edentulous distal
      space. The aim of this laboratorial study was to evaluate an acrylic resin
      cantilever-type prosthesis regarding the flexural strength of its in-balance
      portion as a function of its extension variation and reinforcement by two types
      of fibers (glass and polyaramid), considering that literature is not conclusive
      on this subject. Each specimen was composed by 3 total crowns at its mesial
      portion, each one attached to an implant component (abutment), while the distal
      portion (cantilever) had two crowns. Each specimen was constructed by injecting
      acrylic resin into a two-part silicone matrix placed on a metallic base. In each
      specimen, the crowns were fabricated with either acrylic resin (control group) or
      acrylic resin reinforced by glass (Fibrante, Angelus) or polyaramide (Kevlar 49,
      Du Pont) fibers. Compression load was applied on the cantilever, in a point
      located 7, 14 or 21 mm from the distal surface of the nearest crown with
      abutment, to simulate different extensions. The specimen was fixed on the
      metallic base and the force was applied until fracture in a universal test
      machine. Each one of the 9 sub-groups was composed by 10 specimens. Flexural
      strength means (in kgf) for the distances of 7, 14 and 21 mm were, respectively,
      28.07, 8.27 and 6.39 for control group, 31.89, 9.18 and 5.16 for Kevlar 49 and
      30.90, 9.31 and 6.86 for Fibrante. Data analysis ANOVA showed statistically
      significant difference (p<0.05) only regarding cantilever extension. Tukey's test
      detected significantly higher flexural strength for the 7 mm-distance, followed
      by 14 and 21 mm. Fracture was complete only on specimens of non-reinforced
      groups.

PMID- 19089202
TI  - Electromyographic evaluation of mastication and swallowing in elderly individuals
      with mandibular fixed implant-supported prostheses.
AB  - This study evaluated the effect of implant-supported oral rehabilitation in the
      mandible on the electromyographic activity during mastication and swallowing in
      edentulous elderly individuals. Fifteen patients aged more than 60 years were
      evaluated, being 10 females and 5 males. All patients were edentulous, wore
      removable complete dentures on both dental arches, and had the mandibular
      dentures replaced by implant-supported prostheses. All patients were submitted to
      electromyographic evaluation of the masseter, superior orbicularis oris muscles,
      and the submental muscles, before surgery and 3, 6 and 18 months postoperatively,
      using foods of different textures. The results obtained at the different periods
      were analyzed statistically by Kruskal-Wallis non-parametric test. Statistical
      analysis showed that only the masseter muscle had a significant loss in
      electromyographic activity (p<0.001), with a tendency of similar response for the
      submental muscles. Moreover, there was an increase in the activity of the
      orbicularis oris muscle during rubber chewing after treatment, yet without
      statistically significant difference. Mandibular fixed implant-supported
      prostheses in elderly individuals revealed a decrease in electromyographic
      amplitude for the masseter muscles during swallowing, which may indicate
      adaptation to new conditions of stability provided by fixation of the complete
      denture in the mandibular arch.

PMID- 19089204
TI  - Immediate and delayed solubility of mineral trioxide aggregate and Portland
      cement.
AB  - This study investigated the solubility of mineral trioxide aggregate (MTA) and
      Portland cement since its mixture until 672 hours, by means of two complimentary
      methods. Metal ring molds filled with the cements were covered with distilled
      water and, at each experimental time (3, 24, 72, 168, 336 and 672 hours), were
      weighed as soon as the plates in which the samples have been placed. Empty rings
      served as the control group (n=8). Mean weight gain and loss was determined and
      analyzed statistically by two-way ANOVA and Tukey's test for all pairwise
      comparisons. Only Portland cement showed less than 3% weight loss through 24
      hours. Detached MTA residues were heavier than those of Portland cement over the
      3 to 168 hours. The weight of MTA rings increased more than that of Portland
      rings within 672 hours (p=0.05). The findings of the present study indicate that,
      in an aqueous environment MTA is more soluble than Portland cement and exceeds
      the maximum weight loss considered acceptable by ISO 6876 standard (2001).

PMID- 19089203
TI  - Bone regeneration after demineralized bone matrix and castor oil (Ricinus
      communis) polyurethane implantation.
AB  - Innocuous biocompatible materials have been searched to repair or reconstruct
      bone defects. Their goal is to restore the function of live or dead tissues. This
      study compared connective tissue and bone reaction when exposed to demineralized
      bovine bone matrix and a polyurethane resin derived from castor bean (Ricinus
      communis). Forty-five rats were assigned to 3 groups of 15 animals (control,
      bovine bone and polyurethane). A cylindrical defect was created on mandible base
      and filled with bovine bone matrix and the polyurethane. Control group received
      no treatment. Analyses were performed after 15, 45 and 60 days (5 animals each).
      Histological analysis revealed connective tissue tolerance to bovine bone with
      local inflammatory response similar to that of the control group. After 15 days,
      all groups demonstrated similar outcomes, with mild inflammatory reaction,
      probably due to the surgical procedure rather than to the material. In the
      polymer group, after 60 days, scarce multinucleated cells could still be
      observed. In general, all groups showed good stability and osteogenic connective
      tissue with blood vessels into the surgical area. The results suggest
      biocompatibility of both materials, seen by their integration into rat mandible.
      Moreover, the polyurethane seems to be an alternative in bone reconstruction and
      it is an inexhaustible source of biomaterial.

PMID- 19089205
TI  - Optical density and chemical composition of microfilled and microhybrid composite
      resins.
AB  - This study evaluated the optical density of two microfilled and two microhybrid
      resins, as well as the composition of these materials with regard to their
      optical density. Cavities prepared in 12 2-mm- or 4-mm-thick acrylic plastic
      plates were filled with Z250 (3M-ESPE), A110 (3M-ESPE), Charisma (Heraeus-Kulzer)
      and DurafillVS (Heraeus-Kulzer). The resin increments (2-mm-thick) were light
      cured for 40 s. Three 0.12-s radiographic exposures were made of each #2 acrylic
      plastic plate. DenOptix system optical plates were used to obtain the digital
      images. Three readings of the composite resin surface were made in each
      radiograph, totalizing 216 readings. The mean of highest and lowest grey-scale
      values was obtained. Two specimens of each composite resin were prepared for SEM
      analysis of the chemical elements related to optical density, using energy
      dispersive x-ray analysis (EDX). The results were subjected to Shapiro-Wilk's
      test, ANOVA, Tukey's test at 1% level of significance and Pearson's correlation.
      The mean grey-scale values at 2 mm and 4 mm were: Z250 = 154.27a and 185.33w;
      A110 = 46.77b and 63.05y; Charisma = 163.40c and 200.46z; DurafillVS = 43.92b and
      58.99x, respectively. Pearson's test did not show any positive correlation
      between optical density and percentage weight of optical density chemical
      elements. It was concluded that the microhybrid resins had higher optical density
      means than the microfilled resins; among the evaluated resins, Charisma had the
      highest optical density means.

PMID- 19089206
TI  - Comparison of the biocompatibility of different root canal irrigants.
AB  - The purpose of this study was to compare the reaction of rat subcutaneous
      connective tissue to 0.9% sterile saline, 2.5% sodium hypochlorite (NaOCl), 5.25%
      NaOCl and 2% chlorhexidine gluconate solution or gel. Six circles were demarcated
      on the dorsal skin of 24 male Wistar rats, leaving 2 cm between each circle.
      Using a syringe, 0.1 mL of each root canal irrigant was injected subcutaneously
      into 5 circles. In the 6th circle, the needle of an empty syringe was introduced
      into the skin, but no irrigant was injected (control group). Evaluations were
      undertaken at 2 h, 48 h, 14 days and 30 days post-procedure. Tissue samples were
      excised, embedded in paraffin blocks and 3-microm-thick sections were obtained
      and stained with hematoxylin and eosin. The areas of inflammatory reaction were
      evaluated and analyzed statistically by ANOVA and Tukey's test. The control group
      showed few or no inflammatory reaction areas in the subcutaneous tissue. 0.9%
      saline solution, 2.0% chlorhexidine solution and 2.5% NaOCl showed a good
      biocompatibility, as very mild inflammatory reaction was detected at 14 days and
      tissue repair occurred at 30 days. 5.25% NaOCl was the most toxic irrigant, as
      the number of inflammatory cells remained elevated at 14 and 30 days. The group
      treated with 2.0% chlorhexidine gluconate gel presented a moderate inflammatory
      response at 14 days, which decreased at 30 days, being considered similar to that
      of the control group, 0.9% saline solution, 2.0% chlorhexidine solution and 2.5%
      NaOCl at this experimental period.

PMID- 19089207
TI  - Infrared spectroscopy: a tool for determination of the degree of conversion in
      dental composites.
AB  - Infrared spectroscopy is one of the most widely used techniques for measurement
      of conversion degree in dental composites. However, to obtain good quality
      spectra and quantitative analysis from spectral data, appropriate expertise and
      knowledge of the technique are mandatory. This paper presents important details
      to use infrared spectroscopy for determination of the conversion degree.

PMID- 19089208
TI  - Knowledge and attitude of parents or caretakers regarding transmissibility of
      caries disease.
AB  - Dental caries is a transmissible infectious disease in which mutans streptococci
      are generally considered to be the main etiological agents. Although the
      transmissibility of dental caries is relatively well established in the
      literature, little is known whether information regarding this issue is correctly
      provided to the population. The present study aimed at evaluating, by means of a
      questionnaire, the knowledge and usual attitude of 640 parents and caretakers
      regarding the transmissibility of caries disease. Most interviewed adults did not
      know the concept of dental caries being an infectious and transmissible disease,
      and reported the habit of blowing and tasting food, sharing utensils and kissing
      the children on their mouth. 372 (58.1%) adults reported that their children had
      already been seen by a dentist, 264 (41.3%) answered that their children had
      never gone to a dentist, and 4 (0.6%) did not know. When the adults were asked
      whether their children had already had dental caries, 107 (16.7%) answered yes,
      489 (76.4%) answered no, and 44 (6.9%) did not know. Taken together, these data
      reinforce the need to provide the population with some important information
      regarding the transmission of dental caries in order to facilitate a more
      comprehensive approach towards the prevention of the disease.

PMID- 19089209
TI  - Comparison of two minimally invasive methods on the longevity of glass ionomer
      cement restorations: short-term results of a pilot study.
AB  - The purpose of this study was to evaluate the clinical performance of glass
      ionomer cement (GIC) restorations comparing two minimally invasive methods in
      permanent teeth after 12 months. Fifty pregnant women (second trimester of
      pregnancy), mean age 22 +/- 5.30 years, were treated by two previously trained
      operators. The treatment approaches tested were: chemomechanical method
      (Carisolv; MediTeam) and atraumatic restorative treatment (ART). A split-mouth
      study design was used in which the two treatments were randomly placed in 50
      matched pairs of permanent teeth. The chemomechanical method (CM) was the test
      group and the ART was the control group. The treatments were performed in Public
      Health Centers. The tested restorative material was a high-strength GIC (Ketac
      Molar; 3M/ESPE). The restorations were placed according to the ART guidelines.
      Two calibrated independent examiners evaluated the restorations in accordance
      with ART criteria. The inter-examiner kappa was 0.97. Data were analyzed using
      95% confidence interval on the binomial distribution and Fisher's exact test at
      5% significance level. In a 12-month follow-up, 86% of the restorations were
      evaluated. In the test group (CM), 100% (CI=93.3-100%) of the restorations were
      considered successful. In the control group (ART) 97.6% (CI=87.4-99.9%) of the
      restorations were considered successful and 2.4% unsuccessful (marginal defect
      >0.5 mm). There was no statistically significant difference between the 12-month
      success rate for both groups (Fisher's exact test: P=0.49) and between the two
      operators (Fisher's exact test: P=1.00). Both minimally invasive methods,
      chemomechanical method and ART, showed a similar clinical performance after 12
      months of follow up.

PMID- 19089210
TI  - Relationship between the degree of conversion, solubility and salivary sorption
      of a hybrid and a nanofilled resin composite.
AB  - This study analyzed the relationship between the degree of conversion (DC),
      solubility, and salivary sorption of a hybrid (Filtek P 60) and a nanofilled
      resin composite (Filtek Supreme), and evaluated the influence of the light
      activation mode on these properties. Two light-activation modes were used:
      Conventional (C; 850 mW/cm(2) for 20 s) and Soft-start (SS; 100-1,000 mW/cm(2)
      for 10 s + 1,000 mW/cm(2) for 10 s). The DC (%) was evaluated by FT-Raman
      spectroscopy. The solubility and salivary sorption were measured after immersion
      in artificial saliva for 7 days. Data were analyzed by ANOVA and Student-Newman
      Keuls' test and linear regression analysis (a = 0.05). The DC varied from 50.52%
      (nanofilled composite) to 57.15% (hybrid composite), and was influenced by the
      light-activation mode: C > SS. The solubility (0.45 microg/mm(3)) and salivary
      sorption (8.04 microg/mm(3)) of the nanofilled composite were greater than those
      of the hybrid composite (0.40 microg/mm(3) / 6.87 microg/mm(3)), and were
      influenced by the light-activation mode: SS > C. Correlation was found between DC
      and solubility (r = - 0.89, p<0.05), as well as between solubility and salivary
      sorption (r = 0.95). These findings suggest that nanofilled composites may
      present higher degradation in the oral environment than hybrid ones. Soft-start
      light-activation mode may increase the solubility of resin composites.

PMID- 19089211
TI  - Comparison of radiographic measurements obtained with conventional and indirect
      digital imaging during endodontic treatment.
AB  - The aims of this study were to evaluate the quality of indirect digitized
      radiographic images taken during endodontic procedures and to compare the
      measurements recorded with this technique to those obtained from conventional
      radiographs. Two-hundred conventional periapical radiographs taken at the
      undergraduate Endodontics Clinic of the Dental School of Bauru were digitized.
      The conventional and indirect digitized images were compared by three examiners
      as to the quality and accuracy of the measurements recorded during endodontic
      treatment, in canal length determination, gutta-percha adaptation, lateral
      condensation and final obturation. The conventional radiographs were observed on
      a film viewer, surrounded by a dark card, and measured with magnifying glass and
      a millimeter ruler; the indirect digitized images were evaluated on the Digora
      for Windows software, with free utilization of the bright/contrast tool. Unlike
      the conventional radiographic images, all indirect digitized images were
      considered as having a high quality. The distance between the filling material
      and the root apex was 0.117 mm larger, on average, for the Digora system
      (p<0.01). The measurements achieved by the investigated radiographic methods were
      clinically similar and they are thus equivalent. Changes in brightness and
      contrast of the images using Digora software improved the diagnosis.

PMID- 19089212
TI  - The Cochrane Collaboration and Oral Health: a Brazilian experience.

PMID- 19089214
TI  - In vitro wear resistance of three types of polymethyl methacrylate denture teeth.
AB  - The wear resistance of denture teeth is important to the longevity of removable
      prostheses of edentulous patients. The ability of denture teeth to maintain a
      stable occlusal relationship over time may be influenced by this property. The
      purpose of this in vitro study was to evaluate the wear resistance of polymethyl
      methacrylate (PMMA) denture teeth based on their chemical composition when
      opposed by a ceramic antagonist. The maxillary canines (n=10) of 3 PMMA denture
      teeth (Trubyte Biotone, cross-linked PMMA; Trilux, highly cross-linked IPN
      (interpenetrating polymer network)-PMMA; and Vivodent, highly cross-linked PMMA)
      were secured in an in vitro 2-body wear-testing apparatus that produced sliding
      contact of the specimens (4.5 cycles/s, sliding distance of 20 mm, under 37
      degrees C running water) against glazed or airborne particle abraded ceramic.
      Wear resistance was measured as height loss (mm) under 300 g (sliding force)
      after 100,000 cycles, using a digital measuring microscope. Mean values were
      analyzed by 2-way ANOVA and Tukey's test (a=0.05). The wear of Trubyte Biotone
      (0.93 +/- 0.14 mm) was significantly higher than that of both other types of
      teeth tested against abraded ceramic (p<0.05). The Vivodent tooth (0.64 +/- 0.17
      mm) exhibited the best wear resistance among the denture teeth tested against
      airborne particle abraded ceramic. There were no statistically significant
      differences (p>0.05) in wear among the 3 denture teeth evaluated against glazed
      ceramic. Trilux and Vivodent teeth tested against either glazed or airborne
      particle abraded ceramic did not differ significantly from each other (p<0.05).
      All teeth showed significantly more wear against airborne particle abraded
      ceramic than against glazed ceramic (p<0.05). In conclusion, the three types of
      PMMA denture teeth presented significantly different wear resistance against the
      abraded ceramic. The high-strength PMMA denture teeth were more wear-resistant
      than the conventional PMMA denture tooth.

PMID- 19089213
TI  - Dealing with dental implant failures.
AB  - An implant-supported restoration offers a predictable treatment for tooth
      replacement. Reported success rates for dental implants are high. Nevertheless,
      failures that mandate immediate implant removal do occur. The consequences of
      implant removal jeopardize the clinician's efforts to accomplish satisfactory
      function and esthetics. For the patient, this usually involves further cost and
      additional procedures. The aim of this paper is to describe different methods and
      treatment modalities to deal with dental implant failure. The main topics for
      discussion include identifying the failing implant, implants replacing failed
      implants at the exact site, and the use of other restorative options.When an
      implant fails, a tailor made treatment plan should be provided to each patient
      according to all relevant variables. Patients should be informed regarding all
      possible treatment modalities following implant failure and give their consent to
      the most appropriate treatment option for them.

PMID- 19089215
TI  - Nasoendoscopy of velopharynx before and during diagnostic therapy.
AB  - Nasoendoscopy is an important tool for assessing velopharyngeal function. The
      purpose of this study was to analyze velar and pharyngeal wall movement and
      velopharyngeal gap during nasoendoscopic evaluation of the velopharynx before and
      during diagnostic therapy. Nasoendoscopic recordings of 10 children with operated
      cleft lip and palate were analyzed according to the International Working Group
      Guidelines. Ratings of movement of velum and pharyngeal walls, and size, location
      and shape of gaps were analyzed by 3 speech-language pathologists (SLPs). Imaging
      was obtained during repetitions of the syllable /pa/ during a single
      nasoendoscopic evaluation: (a) before diagnostic therapy, and (b) after the
      children were instructed to impound and increase intraoral air pressure
      (diagnostic therapy). Once the patients impounded and directed air pressure
      orally, the displacement of the velum, right, left and posterior pharyngeal walls
      increased 40, 70, 80, and 10%, respectively. Statistical significance for
      displacement was found only for right and left lateral pharyngeal walls.
      Reduction in gap size was observed for 30% of the patients and other 40% of the
      gaps disappeared. Changes in gap size were found to be statistically significant
      between the two conditions. In nasoendoscopic assessment, the full potential of
      velopharyngeal displacement may not be completely elicited when the patient is
      asked only to repeat a speech stimulus. Optimization of information can be done
      with the use of diagnostic therapy's strategies to manipulate VP function.
      Assuring the participation of the SLP to conduct diagnostic therapy is essential
      for management of velopharyngeal dysfunction.

PMID- 19089216
TI  - Influence of energy density of different light sources on Knoop hardness of a
      dual-cured resin cement.
AB  - The purpose of this study was to evaluate the Knoop hardness of a dual-cured
      resin-based luting cement irradiated with different light sources as well energy
      density through a ceramic sample. Three light-curing unit (LCUs) were tested:
      tungsten halogen light (HAL), light-emitting diode (LED) and xenon plasma-arc
      (PAC) lamp. Disc-shaped specimens were fabricated from a resin-based cement
      (Enforce). Three energy doses were used by modifying the irradiance (I) of each
      LCU and the irradiation time (T): 24 Jcm(-2) (I/2x2T), 24 Jcm(-2) (IxT) and 48
      Jcm(-2) (Ix2T). Energy doses were applied through a 2.0-mm-thick ceramic sample
      (Duceram Plus). Three groups underwent direct irradiation over the resin cement
      with the different LCUs and a chemically-activated group served as a control.
      Thirteen groups were tested (n=10). Knoop hardness number (KHN) means were
      obtained from cross-sectional areas. Two-way ANOVA and the Holm-Sidak method were
      used for statistical comparisons of activation mode and energy doses (alpha=5%).
      Application of 48 J.cm(-2) energy dose through the ceramic using LED (50.5+/-2.8)
      and HAL (50.9+/-3.7) produced significantly higher KHN means (p<0.05) than the
      control (44.7+/-3.8). LED showed statistically similar performance to HAL. Only
      HAL showed a relationship between the increase of LCU energy dose and hardness
      increase.

PMID- 19089217
TI  - Prenatal dental care: evaluation of professional knowledge of obstetricians and
      dentists in the cities of Londrina/PR and Bauru/SP, Brazil, 2004.
AB  - The purpose of this study was to assess the current knowledge and recommendations
      of obstetricians and dentists as to the dental care to pregnant patients in the
      cities of Londrina/PR and Bauru/SP, Brazil. Questionnaires were distributed to
      professionals of both cities, arguing on the following issues: oral health during
      pregnancy; contact between prenatal care and dental care providers; prenatal
      fluoride supplementation; selection of therapeutic agents for local anesthesia,
      pain control and treatment of infection; and dental procedures that can be
      performed during each trimester. Data were analyzed by frequency of responses and
      statistical analyses were carried out using X(2) (type of workplace/service) and
      t test (time since graduation), significant if p<0.05. Seventy-nine obstetricians
      and 37 dentists responded the questionnaires. Most physicians referred the
      patient to dental care only when a source of dental problem was mentioned,
      limiting the adoption of a preventive approach. Forty-three percent of dentists
      and 34% of obstetricians did not know the potential contribution of periodontal
      infection as a risk factor for preterm low birth-weight babies. There was
      divergence from scientific literature as to the recommendation of local
      anesthetics (dentists and obstetricians), prenatal fluoride supplementation
      (obstetricians) and dental radiographs (dentists). The findings of this survey
      with dentists and obstetricians showed that dental management during pregnancy
      still presents some deviations from scientific literature recommendations,
      indicating the need to update these health care professionals in order to
      establish guidelines for prenatal dental care.

PMID- 19089219
TI  - Presence of bacteria in dentinal tubules.
AB  - This study demonstrated that a significant number of bacteria is present in the
      radicular dentinal tubules of periodontally diseased human teeth. Ten
      periodontally diseased teeth were prepared and stained by Brown and Brenn
      technique for histological examination. Bacteria were detected in all teeth. It
      is suggested that bacteria may invade dentinal tubules exposed to periodontal
      pocket and are very hard to be eliminated by conventional mechanical and chemical
      periodontal therapy. Contaminated dentinal tubules of periodontally diseased
      teeth can thus act as active bacterial reservoirs to promote recolonization of
      mechanically treated root surfaces, which could interfere with the periodontal
      healing and progression of the disease.

PMID- 19089218
TI  - Enamel susceptibility to red wine staining after 35% hydrogen peroxide bleaching.
AB  - Concern has been expressed regarding the staining of enamel surface by different
      beverages after bleaching. This study investigated the influence of 35% hydrogen
      peroxide bleaching agents on enamel surface stained with wine after whitening
      treatments. Flat and polished bovine enamel surfaces were submitted to two
      commercially available 35% hydrogen peroxide bleaching agents or kept in 100%
      humidity, as a control group (n = 10). Specimens of all groups were immersed in
      red wine for 48 h at 37 degrees C, immediately, 24 h or 1 week after treatments.
      All specimens were ground into powder and prepared for the spectrophotometric
      analysis. Data were subjected to two-way analysis of variance and Fisher's PLSD
      test at 5% significance level. The amount of wine pigments uptake by enamel
      submitted to bleaching treatments was statistically higher than that of control
      group, independently of the evaluation time. Results suggested that wine staining
      susceptibility was increased by bleaching treatments.

PMID- 19089220
TI  - Pulpal temperature increase with high-speed handpiece, Er:YAG laser and
      ultrasound tips.
AB  - The aim of this study was to compare intrapulpal temperature increase produced by
      high-speed handpiece, Er:YAG laser and CVDentus ultrasound tips during cavity
      preparation. Thirty bovine mandibular incisors with an enamel/dentin thickness of
      4 mm at buccal surface had their roots amputated and were allocated to the
      following groups (n=10): Group I- high-speed handpiece; Group II- noncontact
      Er:YAG laser (250 mJ/4 Hz); and Group III- CVDentus ultrasouns tips. All devices
      were used with water cooling. Class V cavities were prepared to a depth of 3.5
      mm, measured with a periodontal probe. A type T thermocouple was placed inside
      the pulp chamber to determine the temperature increase (degrees C), which was
      recorded by a data acquisition system ADS 2000 IP (Lynx Technology) linked to a
      notebook computer. Data were analyzed statistically by one-way ANOVA and Tukey's
      test (p=0.05). The mean temperature rises were: 1.10 degrees C (+/-0.56) for
      Group I, 0.84 degrees C (+/-0.55) for Group II, and 3.00 degrees C (+/- 1.34) for
      Group III. There were no statistically significant differences (p>0.05) between
      Groups I and II, but both of them differed significantly from Group III (p<0.05).
      In conclusion, the use of Er:YAG laser and high-speed handpiece for cavity
      preparation resulted in similar temperature increase. Although ultrasound tips
      generated significantly higher intrapulpal temperature increase, it remained
      below the critical value of 5.5 degrees C and may be considered safe for use.

PMID- 19089221
TI  - Influence of application site of provisional cement on the marginal adaptation of
      provisional crowns.
AB  - INTRODUCTION: Marginal discrepancies may lead to cement washout and marginal
      leakage, damaging periodontal and pulp tissues or causing premature loss of the
      restoration. PURPOSE: This study evaluated the influence of application site of
      provisional cement on the marginal adaptation of provisional crowns. MATERIAL AND
      METHODS: Four different application sites of provisional cement (Temp Bond NE,
      Kerr Corporation) were used for cementation of provisional crowns on phantom
      teeth prepared for full crown restorations, performing 4 experimental groups
      (n=10): cement applied to all internal surfaces of the crown (CAO); cement
      applied to all internal surfaces of the crown, except for the occlusal surface
      (CA); cement applied to the cervical crown margin (CM); and cement applied to the
      cervical tooth margin (TM). A comparison microscope (Mitutoyo America
      Corporation) was used to measure the distances between the internal tangents of
      two circular marks, one made on the provisional crown and one made apical to the
      tooth preparation margin, in areas corresponding to buccal, lingual, mesial and
      distal surfaces. Marginal adaptation was determined before and after cementation,
      with 0.0001-mm accuracy. Data were analyzed statistically by ANOVA and Tukey's
      test at 5% significance level. RESULTS: Mean values of marginal opening obtained
      for each group were: CAO: 145 microm; CA: 67 microm; CM: 46 microm; TM: 34
      microm. CA, CM and TM presented significantly lower marginal openings than CAO
      (p<0.05). CONCLUSION: complete filling of the crown with provisional cement,
      including the occlusal surface, provided greater marginal discrepancies when
      compared to the other methods evaluated.

PMID- 19089222
TI  - Evaluation of tissue response to periodontal dressings: histological study in
      tooth sockets of rats.
AB  - Although the use of periodontal dressings is currently limited, there are some
      indications for their use. Selection of any material that will have direct
      contact with live tissues, such as periodontal dressings, should be careful in
      order to allow surgical wound healing. The aim of this study was to evaluate the
      intensity of inflammatory response and bone formation in tooth sockets of rats
      after implantation of three periodontal dressings. After removal of the right
      maxillary incisors of 84 male rats, each tooth socket received implantation of a
      polyethylene tube, 63 of which were filled with non-eugenol periodontal dressing
      and the remaining 21 tubes remained empty (control group). Histological
      evaluation assessed the intensity of inflammatory response and presence and
      location of bone tissue formation at postoperative periods of 7, 14 and 28 days.
      Statistical analysis was performed by the Kruskal-Wallis test at 5% significance
      level. Regarding the inflammatory infiltrate, at 28 days, there was statistically
      significant difference between one of periodontal dressings and control group
      (p<0.05). Analysis of postoperative periods, showed that the control group
      presented statistically significant reduction in the inflammatory infiltrate
      comparing the 14- and 28-day periods (p<0.05). Regarding bone tissue formation,
      there was difference in control group between the 7- and 28-day periods (p<0.05).
      Within the experimental conditions, it may be concluded that no differences were
      found in the inflammatory response among the groups at 7 and 14 days and that
      Voco pac dressing induced a more intensive inflammatory reaction at 28 days.

PMID- 19089223
TI  - Oral myofunctional and electromyographic evaluation of the orbicularis oris and
      mentalis muscles in patients with class II/1 malocclusion submitted to first
      premolar extraction.
AB  - OBJECTIVE: The aim of this study was to assess the presence of oral myofunctional
      alterations before and after first premolar extraction in Class II/1 malocclusion
      patients that could endanger the long-term dental arch stability. MATERIAL AND
      METHODS: The study was performed by means of morphological, functional and
      electromyographic analyses in 17 Class II/1 malocclusion patients (group T) and
      17 Class I malocclusion patients (group C -control), both groups with 12-30-year
      age range (mean age: 20.93 +/- 4.94 years). RESULTS: Data analyzed statistically
      by Student's t-test showed a significant decrease (p<0.05) in the maxillary and
      mandibular dental arch perimeters after orthodontic treatment, but lip posture at
      rest did not present statistically significant differences after treatment
      (p>0.05). The Kruskal-Wallis test analyzed data from lip posture (orbicularis
      oris muscle) at rest and during swallowing, as well as the mentalis muscle
      behavior during the above-mentioned function, not showing statistically
      significant differences (p>0.05) after treatment (groups T1 and T2). However,
      group T differed significantly from group C (p<0.05). Lip posture during
      swallowing showed statistically significant differences (p<0.05) for subjects
      submitted to orthodontic therapy when compared to data acquired before the
      treatment. The electromyographic analysis confirmed these data. CONCLUSIONS:
      Found myofunctional alterations observed after the orthodontic treatment in Class
      II/1 malocclusion seemed to jeopardize the long-term orthodontic stability,
      making recurrence possible.

PMID- 19089225
TI  - Journal of Applied Oral Science. Editorial.

PMID- 19089224
TI  - Influence of different adhesive systems on the pull-out bond strength of glass
      fiber posts.
AB  - This in vitro study evaluated the tensile bond strength of glass fiber posts
      (Reforpost - Angelus-Brazil) cemented to root dentin with a resin cement (RelyX
      ARC - 3M/ESPE) associated with two different adhesive systems (Adper Single Bond 
      3M/ESPE and Adper Scotchbond Multi Purpose (MP) Plus - 3M/ESPE), using the pull
      out test. Twenty single-rooted human teeth with standardized root canals were
      randomly assigned to 2 groups (n=10): G1- etching with 37% phosphoric acid gel
      (3M/ESPE) + Adper Single Bond + #1 post (Reforpost - Angelus) + four #1 accessory
      posts (Reforpin - Angelus) + resin cement; G2- etching with 37% phosphoric acid
      gel + Adper Scotchbond MP Plus + #1 post + four #1 accessory posts + resin
      cement. The specimens were stored in distilled water at 37 degrees C for 7 days
      and submitted to the pull-out test in a universal testing machine (EMIC) at a
      crosshead speed of 0.5 mm/min. The mean values of bond strength (kgf) and
      standard deviation were: G1- 29.163 +/- 7.123; G2- 37.752 +/-13.054. Statistical
      analysis (Student's t-test; a=0.05 showed no statistically significant difference
      (p<0.05) between the groups. Adhesive bonding failures between resin cement and
      root canal dentin surface were observed in both groups, with non-polymerized
      resin cement in the apical portion of the post space when Single Bond was used
      (G1). The type of adhesive system employed on the fiber post cementation did not
      influence the pull-out bond strength.

PMID- 19089226
TI  - Fibrin adhesive derived from snake venom in periodontal surgery: histological
      analysis.
AB  - BACKGROUND: A new fibrin adhesive made of buffalo plasma-derived fibrinogen and a
      thrombin-like snake venom enzyme, has been successfully used to immobilize free
      gingival grafts. This case series histologically compared sutured grafts (control
      group) with others immobilized by using the fibrin adhesive (experimental group).
      CASE DESCRIPTION: The grafts were placed in the contralateral mandibular
      bicuspids of 15 patients, so that each subject received one treatment of each
      type. Five biopsies of each group were collected at 7, 14 and 45 days of healing,
      which were histologically and morphometrically analyzed as regards the relative
      volume density of the different connective tissue components. RESULTS: The sites
      in the control group presented a higher inflammatory cell density at 7 days and a
      tendency towards a lower collagen density. In the experimental group, the grafts
      had an appearance of more advanced healing. Tissue maturity characteristics
      progressed until 14 and 45 days, but no difference between groups could be noted
      at these times. CONCLUSIONS: Within the limits of the present study, it may be
      suggested that the alternative fibrin adhesive tested could represent an
      alternative to sutures in gingival grafts procedures.

PMID- 19089227
TI  - Repair process of surgical defects filled with autogenous bone grafts in tibiae
      of diabetic rats.
AB  - From a biological standpoint, the best material for reconstruction of bone
      defects is the autogenous bone graft. However, as tissue healing is affected
      under diabetic conditions, major changes might take place in the
      revascularization, incorporation, replacement and remodeling phases of the
      grafted area. The purpose of this study was to assess the bone healing process in
      surgical wounds prepared in tibiae of diabetic rats and filled with autogenous
      bone. Forty male rats (Rattus norvegicus albinus, Wistar) were randomly assigned
      to receive an endovenous injection (penile vein) of either citrate buffer
      solution (Group 1 - control; n=20) or streptozotocin dissolved in citrate buffer
      solution (35 mg/kg) to induce diabetes (Group 2 - diabetic; n=20). After
      determination of glycemia, the animals were anesthetized and the anterolateral
      regions of the tibiae of both limbs were shaved, antisepsis was performed and
      longitudinal incisions were made in each limb. The tibiae were exposed and two
      2mm-diameter surgical cavities were prepared: one in the right limb, filled with
      particulate autogenous bone and the other in the left limb, filled with blood
      clot. The animals were euthanized at 10 and 30 postoperative days. The anatomic
      pieces were obtained, submitted to laboratory processing and sections were
      stained by hematoxylin and eosin and Masson's Trichrome for histomorphologic and
      histometric analyses. In both groups, the wounds filled with autogenous bone
      graft showed better results than those filled with blood clot. The control group
      showed higher new bone formation in wounds filled with autogenous bone graft at
      30 days than the diabetic group, but without statistical significance. It may be
      concluded that, in general, the new bone formation occurred with autogenous graft
      was quantitatively similar between control and diabetic groups and qualitatively
      better in the control group.

PMID- 19089228
TI  - A computational method for recording and analysis of mandibular movements.
AB  - This study proposed the development of a new clinical tool capable of quantifying
      the movements of opening-closing, protrusion and laterotrusion of the mandible.
      These movements are important for the clinical evaluation of the
      temporomandibular function and muscles involved in mastication. Unlike current
      commercial systems, the proposed system employs a low-cost video camera and a
      computer program that is used for reconstructing the trajectory of a reflective
      marker that is fixed on the mandible. In order to illustrate the clinical
      application of this tool, a clinical experiment consisting on the evaluation of
      the mandibular movements of 12 subjects was conducted. The results of this study
      were compatible with those found in the literature with the advantage of using a
      low cost, simple, non-invasive, and flexible tool customized for the needs of the
      practical clinic.

PMID- 19089229
TI  - Fracture strength of different soldered and welded orthodontic joining
      configurations with and without filling material.
AB  - The aim of this study was to compare the mechanical strength of different joints
      made by conventional brazing, TIG and laser welding with and without filling
      material. Five standardized joining configurations of orthodontic wire in spring
      hard quality were used: round, cross, 3 mm length, 9 mm length and 7 mm to
      orthodontic band. The joints were made by five different methods: brazing,
      tungsten inert gas (TIG) and laser welding with and without filling material. For
      the original orthodontic wire and for each kind of joint configuration or
      connecting method 10 specimens were carefully produced, totalizing 240. The
      fracture strengths were measured with a universal testing machine (Zwick 005).
      Data were analyzed by ANOVA (p=0.05) and Bonferroni post hoc test (p=0.05). In
      all cases, brazing joints were ruptured on a low level of fracture strength (186
      407 N). Significant differences between brazing and TIG or laser welding (p<0.05,
      Bonferroni post hoc test) were found in each joint configuration. The highest
      fracture strength means were observed for laser welding with filling material and
      3 mm joint length (998 N). Using filling materials, there was a clear tendency to
      higher mean values of fracture strength in TIG and laser welding. However,
      statistically significant differences were found only in the 9-mm long joints
      (p<0.05, Bonferroni post hoc test). In conclusion, the fracture strength of
      welded joints was positively influenced by the additional use of filling
      material. TIG welding was comparable to laser welding except for the
      impossibility of joining orthodontic wire with orthodontic band.

PMID- 19089230
TI  - Maximum inhibitory dilution of mouthwashes containing chlorhexidine and
      polyhexamethylene biguanide against salivary Staphylococcus aureus.
AB  - OBJECTIVE: The aim of the present study was to determine the in vitro maximum
      inhibitory dilution (MID) of two chlorhexidinebased oral mouthwashes (CHX):
      Noplak, Periogard, and one polyhexamethylene biguanide-based mouthwash (PHMB):
      Sanifill Premium against 28 field Staphylococcus aureus strains using the agar
      dilution method. MATERIALS AND METHODS: For each product, decimal dilutions
      ranging from 1/10 to 1/655,360 were prepared in distilled water and added to
      Mueller Hinton Agar culture medium. After homogenization, the culture medium was
      poured onto Petri dishes. Strains were inoculated using a Steers multipoint
      inoculator and dishes were incubated at 37 degrees C for 24 hours. For reading,
      MID was considered as the maximum dilution of the mouthwash still capable of
      inhibiting microbial growth. RESULTS: Sanifill Premium inhibited the growth of
      all strains at 1/40 dilution and of 1 strain at 1/80 dilution. Noplak inhibited
      the growth of 23 strains at 1/640 dilution and of all 28 strains at 1/320
      dilution. Periogard showed inhibited growth of 7 strains at 1/640 dilution and of
      all 28 strains at 1/320 dilution. Data were submitted to Kruskal-Wallis
      statistical test, showing significant differences between the mouthwashes
      evaluated (p<0.05). No significant difference was found between Noplak and
      Periogard (p>0.05). Sanifill Premium was the least effective (p<0.05).
      CONCLUSION: It was concluded that CHX-based mouthwashes present better
      antimicrobial activity against S. Aureus than the PHMB-based mouthwash.

PMID- 19089231
TI  - Detection of HPV DNA and immunohistochemical expression of cell cycle proteins in
      oral carcinoma in a population of Brazilian patients.
AB  - This study investigated the presence of human papillomavirus (HPV) DNA and viral
      types in 33 cases of oral squamous cells carcinoma (OSCC) and compared the
      immunohistochemical expression of the cell-cycle markers p21 and pRb between
      cases of the disease with and without HPV. DNA was extracted from paraffin
      embedded tissue and amplified by PCR for the detection of HPV DNA. Viral typing
      was performed by dot blot hybridization. Immunohistochemistry was performed by
      the streptavidinbiotin technique. HPV DNA was detected in 11 (33.33%) of the 33
      cases. The prevalent viral type was HPV 18 (81.81%). A significant association
      was observed between the presence of HPV and immunohistochemical expression of
      pRb, but not between p21 expression and the presence of the virus. The low
      frequency of detection of HPV DNA in OSCC suggests a possible participation of
      the virus in the development and progression of only a subgroup of these tumors.

PMID- 19089232
TI  - Evaluation of the apical infiltration after root canal disruption and obturation.
AB  - The aim of this study was to evaluate two root canal filling techniques used in
      teeth that had their apical foramen disrupted and compare the apical infiltration
      with an ideal clinical situation. Twenty-seven freshly extracted single-rooted
      teeth were selected and radiographed to confirm the existence of a single and
      straight root canal. The crowns were removed at a mean distance of 11 mm from the
      apex. The teeth had the root canals instrumented and were randomly assigned to 3
      groups (n=9): ND group - root canals were filled using the lateral compaction
      technique and no disruption was performed; DRF group - the apical constriction
      was disrupted by advancing a #40 K-file 1 mm beyond the original working length,
      the canals were reinstrumented to create an apical ledge at 1 mm from the apical
      foramen and were obturated with a master gutta-percha cone with same size as the
      last file used for reinstrumentation; DF group - the teeth had the apical
      constriction disrupted and the canals were obturated with a master gutta-percha
      cone that fit at 1 mm from the apex. The teeth were submitted to dye leakage test
      with Rhodamine B for 7 days, using vaccum on the initial 5 min. The teeth were
      sectioned longitudinally and the leakage was measured in a linear fashion from
      apex to crown. There was no statistically significant difference (p>0.05) between
      the groups that had the apical foramen disrupted (DF, DRF), but significant
      difference was found between the disrupted groups and the non-disrupted one
      (p<0.01). In conclusion, none of the evaluated techniques was able to prevent
      apical infiltration, so working length so the working length determination has to
      be established and maintained carefully.

PMID- 19089233
TI  - Evaluation of the effects of processing delays and protective plastic cases on
      image quality of a photostimulable phosphor plate system.
AB  - This ex vivo study evaluated the quality of digital radiographic images obtained
      with the photostimulable phosphor plate system (Digora) according to the
      processing delay and maintenance of optical plates in either opaque (supplied
      with the system) or transparent protective plastic cases during this period. Five
      radiographs were obtained from the mandibular molar region of a dry human
      mandible using optical plates. These plates were placed in the protective plastic
      cases before obtaining the radiographs and were processed immediately or after
      processing delays of 5, 60 and 120 min, when the case was removed. The results
      revealed a reduction in image quality when processing was delay 120 min compared
      to the other times. The opaque case provided better protection to the sensor than
      the transparent case. In conclusion, a 120-min processing delay for the Digora
      system caused a reduction in image quality, yet without interfering with the
      quality of diagnosis. The opaque case supplied by the system's manufacturer
      provided better protection to the optical plate than the transparent case.

PMID- 19089234
TI  - In vitro study of the pulp chamber temperature rise during light-activated
      bleaching.
AB  - This study evaluated in vitro the pulp chamber temperature rise induced by the
      light-activated dental bleaching technique using different light sources. The
      root portions of 78 extracted sound human mandibular incisors were sectioned
      approximately 2 mm below the cementoenamel junction. The root cavities of the
      crowns were enlarged to facilitate the correct placing of the sensor into the
      pulp chamber. Half of specimens (n=39) was assigned to receive a 35% hydrogen
      peroxide gel on the buccal surface and the other halt (n=39) not to receive the
      bleaching agent. Three groups (n=13) were formed for each condition (bleach or no
      bleach) according to the use of 3 light sources recommended for dental bleaching:
      a light-emitting diode (LED)laser system, a LED unit and a conventional halogen
      light. The light sources were positioned perpendicular to the buccal surface at a
      distance of 5 mm and activated during 30 s. The differences between the initial
      and the highest temperature readings for each specimen were obtained, and, from
      the temperature changes, the means for each specimen and each group were
      calculated. The values of temperature rise were compared using Kruskal-Wallis
      test at 1% significance level. Temperature rise varied significantly depending on
      the light-curing unit, with statistically significant differences (p<0.01) among
      the groups. When the bleaching agent was not applied, the halogen light induced
      the highest temperature rise (2.38+/-0.66 degrees C). The LED unit produced the
      lowest temperature increase (0.29+/-0.13 degrees C); but there was no significant
      difference between LED unit and LED-laser system (0.35+/-0.15 degrees C)
      (p>0.01). When the bleaching agent was applied, there were significant
      differences among groups (p<0.01): halogen light induced the highest temperature
      rise (1.41+/-0.64 degrees C), and LED-laser system the lowest (0.33+/-0.12
      degrees C); however, there was no difference between LED-laser system and LED
      unit (0.44+/-0.11 degrees C). LED and LED-laser system did not differ
      significantly from each other regardless the temperature rise occurred with or
      without bleaching agent application. It may be concluded that during light
      activated tooth bleaching, with or without the bleaching agent, halogen light
      promoted higher pulp chamber temperature rise than LED unit and LED-laser system.
      The tested light-curing units provided increases in the pulp chamber temperature
      that were compatible with pulpal health.

PMID- 19089236
TI  - Editorial.

PMID- 19089235
TI  - Transmigration of mandibular second premolar in a patient with cleft lip and
      palate--case report.
AB  - Disturbances involving abnormalities in tooth eruption are named ectopia.
      Transmigration is the name assigned to ectopia in the presence of teeth in areas
      distant from the alveolar process. Initial angulation of the tooth bud of the
      second premolar and premature loss of permanent mandibular 1st molars can
      influence the distal migration of the second premolar. Some studies have observed
      that ectopic teeth can be found in a variety of places around the oral cavity and
      also in other areas of the human body. There are records of teeth in the
      maxillary sinus, mandibular condyle, coronoid process, mandibular angle, orbit,
      palate, mentum and also the skin. The prevalence of tooth abnormalities is higher
      in children with cleft lip and palate compared to children without clefts. This
      paper presents a case report of migration of the mandibular left second premolar
      in a patient attending the Hospital for Rehabilitation of Craniofacial Anomalies
      of the University of Sao Paulo (HRAC/USP), Brazil. Migration of the mandibular
      left 2nd premolar was confirmed by 8 panoramic and 1 periapical radiographs
      obtained during patient's treatment between 1978 and 2002, which were available
      in the files of the Department of Dental Radiology of HRAC/USP. It can be assumed
      that distal migration of the mandibular left 2nd premolar is not associated with
      presence of cleft lip and palate; observation of these two events in a same
      patient is rare, since no similar reported cases were found in the literature.

PMID- 19089237
TI  - Effect of surface treatments on the spreading velocity of simplified adhesive
      systems.
AB  - OBJECTIVES: To determine the roughness of glass surfaces submitted to different
      treatments and to correlate it with the spreading velocity of two adhesive
      systems. MATERIALS AND METHODS: Glass slides were used as substrates to evaluate
      the spreading velocity of Single Bond and Prime & Bond NT adhesive systems. Six
      different surface treatments were compared: 1) no treatment; 2) silanization
      (SL); 3) sandblasting (SB); 4) SB + SL; 5) 10% hydrofluoric acid treatment (HF);
      6) HF + SL. Before and after treatments, surface roughness was measured by a
      profilometer (Ra, microm). Drop volumes (10 microl) of the adhesive systems were
      deposited onto substrates with a micropipette to observe materials spreading
      during 30s. Data were expressed in mm/s as spreading velocity. Statistical
      significances among groups were analyzed using one-way and two-way-ANOVA designs
      and the SNK test. RESULTS: Significant differences in spreading velocity were
      found between materials (p < 0.001) and among treatments (p < 0.001).
      Silanization decreased the spreading velocity for both adhesives in comparison to
      groups where it was not performed (p < 0.05). Differences in roughness were found
      only for SB surfaces that were rougher than the others (p < 0.05). Silanization
      decreased the roughness of SB surfaces (p < 0.05). Linear regression did not
      indicate any correlation between spreading velocity and roughness (R = 0.173).
      CONCLUSION: Although surface treatments yielded different roughness, they did not
      provide differences in the spreading velocity of the simplified bonding systems
      studied. Silanization decreased bonding systems' spreading velocities.

PMID- 19089238
TI  - Effect of 2% iodine disinfecting solution on bond strength to dentin.
AB  - INTRODUCTION: Disinfection of dentin surfaces is desirable so long as it does not
      interfere with subsequent bonding of adhesive resins. OBJECTIVE: To test the null
      hypothesis that bond strengths to dentin are not affected by previous application
      of an iodine disinfecting solution. MATERIALS AND METHODS: Twenty-four extracted
      non-carious molars were selected. Occlusal enamel was removed producing a flat
      dentin substrate. Test teeth were all treated with 2% Iodine
      disclosing/disinfecting solution (I(2)DDS) for 20 sec and rinsed for 20 sec
      followed by the application of self- or total- etching bonding systems,
      generating five adhesive groups (n=3): Single Bond; Prime & Bond NT; Clearfil SE
      Bond; Opti-Bond Plus. The control groups (n=3 per adhesive) had no
      disclosing/disinfectant application prior to adhesive application. A 4-mm thick
      resin restoration was built up on each tooth for microtensile testing.
      Statistical analyses between experimental and control groups were performed by
      student's t-test (alpha= 0.05). RESULTS: In general, experimental groups
      (previously treated with I(2)DDS) showed significantly lower bond strength values
      when compared with their respective controls (p<0.05), except for group Prime &
      Bond I(2) that did not significantly differ from its control (p>0.05).
      CONCLUSION: Acetone-base adhesive systems seem not to be affected by the
      application of I(2)DDS prior to etching and bonding procedures.

PMID- 19089239
TI  - Morphometric and microscopic evaluation of the effect of gallium nitrate as a
      root canal dressing in rat teeth submitted to late replantation.
AB  - The purpose of this study was to test a gallium nitrate solution, a resorption
      inhibitor, employed as a root canal dressing in teeth submitted to late
      replantation. Thirty maxillary right central incisors of rats were avulsed and
      kept dry for thirty minutes. The teeth were instrumented and the root surfaces
      were treated with 1% hypochlorite solution followed by application of 2% sodium
      fluoride. Thereafter, the teeth were divided into two groups according to the
      root canal dressing: Group I, solution of gallium nitrate; and Group II, calcium
      hydroxide paste. The teeth were then replanted in their respective sockets. The
      animals were killed at 15, 30 and 60 days after replantation and the samples were
      processed for morphometric and microscopic analysis. The results demonstrated
      that the gallium nitrate solution and the calcium hydroxide paste limited the
      root resorption, yet they did not impair its occurrence. It may be concluded that
      gallium nitrate solution and calcium hydroxide paste demonstrated similar
      performance.

PMID- 19089240
TI  - Evaluating noise in digitized radiographic images by means of histogram.
AB  - To evaluate the performance of three digital devices regarding the noise added to
      digital radiographic images containing different optical densities. METHODS: A
      radiographic image was digitized repeatedly ten times using two scanners (HP 4c/T
      and HP 5370C) and a digital camera (Nikon 990). A histogram tool measured a mean
      pixel value and the standard deviation of the region of interest in each image.
      Both values were used to calculate the image noise at the different optical
      densities. RESULTS: The noise values found were different for all devices and
      optical densities. There was a statistically significant difference (p<0.05)
      between the scanner HP 4c/T and the digital camera regarding the noise values.
      There was a significant correlation (p<0.05) between the noise values found for
      the HP 4c/T scanner and the digital camera and between both scanners (p<0.01).
      CONCLUSION: The noise added to the image was higher for scanner HP 4c/T and less
      for the digital camera. The noise was higher at the lower optical densities for
      the scanners. It seems that depending on the equipment and the optical density, a
      variable amount of noise can be incorporated to the images.

PMID- 19089241
TI  - Influence of image filters on the reproducibility measurements of alveolar bone
      loss.
AB  - The reproducibility of measurements of alveolar bone loss on radiographs may be a
      problem on epidemiologic studies, as they are based on comparisons of the
      diagnosis of various examiners. The aim of the present research paper was to
      assess the inter- and intra-examiner reproducibility of measurements of the
      interproximal alveolar bone loss on non-manipulated digital radiographs and after
      the application of image filters. Five Oral Radiologists measured the distance
      between the cementoenamel junction (CEJ) to the alveolar crest or to the deepest
      point of the bony defect on 12 interproximal digital radiographs of molars and
      bicuspids of a dry human skull. The digital manipulation and the linear
      measurements were obtained with the Trophy Windows software (Throphy). For each
      image, six different versions were created: 1) non-manipulated; 2) bright
      contrast adjustment; 3) negative; 4) negative with brightness-contrast
      adjustment; 5) pseudo-colored; 6) pseudo-colored with brightness-contrast
      adjustment. In order to prevent interpretation bias because of the repetition of
      measurements, the examiners measured the radiographs in a random sequence. The
      two-way ANOVA test at 5% level of significance to compare the means of readings
      of the same operator with each filter indicated p<0.05 for the majority of
      operators, while the comparison between the mean values of operators using the
      same filter indicated p>0.05 for all filters. Based on the results, we concluded
      that linear measurements of interproximal alveolar bone loss on digital
      radiographs are highly reproducible among examiners. Nevertheless, the
      application of image filters significantly influenced the degree of intra
      examiner reproducibility. Some filters even reduced the reproducibility of intra
      examiner readings.

PMID- 19089242
TI  - Speech evaluation with and without palatal obturator in patients submitted to
      maxillectomy.
AB  - Most patients who have undergone resection of the maxillae due to benign or
      malignant tumors in the palatomaxillary region present with speech and swallowing
      disorders. Coupling of the oral and nasal cavities increases nasal resonance,
      resulting in hypernasality and unintelligible speech. Prosthodontic
      rehabilitation of maxillary resections with effective separation of the oral and
      nasal cavities can improve speech and esthetics, and assist the psychosocial
      adjustment of the patient as well. The objective of this study was to evaluate
      the efficacy of the palatal obturator prosthesis on speech intelligibility and
      resonance of 23 patients with age ranging from 18 to 83 years (Mean = 49.5
      years), who had undergone inframedial-structural maxillectomy. The patients were
      requested to count from 1 to 20, to repeat 21 words and to spontaneously speak
      for 15 seconds, once with and again without the prosthesis, for tape recording
      purposes. The resonance and speech intelligibility were judged by 5 speech
      language pathologists from the tape recordings samples. The results have shown
      that the majority of patients (82.6%) significantly improved their speech
      intelligibility, and 16 patients (69.9%) exhibited a significant hypernasality
      reduction with the obturator in place. The results of this study indicated that
      maxillary obturator prosthesis was efficient to improve the speech
      intelligibility and resonance in patients who had undergone maxillectomy.

PMID- 19089243
TI  - SEM analysis of the acid-etched enamel patterns promoted by acidic monomers and
      phosphoric acids.
AB  - OBJECTIVE: Although self-etching bonding systems (SES) are indicated to prepare
      dental enamel for bonding, concerns have been expressed regarding their
      effectiveness. The aim of this study was to analyze the etching pattern (EP) of
      nine SES in comparison with 35% and 34% phosphoric acid etchants (FA) on intact
      (IN) and ground (GR) enamel surface. MATERIALS AND METHODS: Twenty-two human
      third molars were sectioned in mesial-distal and buccal-lingual directions, and
      four dental fragments were obtained from each tooth. Half of the fragments were
      ground using 600-grit SiC paper and the other half remained intact. The fragments
      were randomly assigned into 22 groups, according to the texture of enamel surface
      (IN and GR) and the technique to etch the enamel (34% FA, 35% FA, AdheSE primer;
      Brush & Bond; Clearfil Protect Bond primer; iBond; One-up Bond F; OptiBond Solo
      Plus primer; Tyrian SPE primer; Unifil Bond primer and Xeno III). Conditioners
      were applied to IN and GR enamel surfaces, according to the manufacturer's
      instructions. Specimens etched with phosphoric acids were washed with water,
      while the surfaces treated with SES were submitted to alternate rinsing with
      alcohol and acetone. The specimens were dried, sputter-coated and examined under
      a scanning electron microscope. RESULTS: For both IN and GR enamel surfaces, the
      EP of 34 and 35% FA was deeper and more homogeneous in comparison to EP of SES,
      except for Tyrian SPE. The acidic monomer action of self-etching systems was more
      effective on GR enamel. CONCLUSION: Most of the SES are less aggressive than
      phosphoric acid etchants and their etching effects were reduced on intact enamel
      surfaces.

PMID- 19089244
TI  - Bond strength of hard chairside reline resins to a rapid polymerizing denture
      base resin before and after thermal cycling.
AB  - PURPOSE: This study assessed the shear bond strength of 4 hard chairside reline
      resins (Kooliner, Tokuso Rebase Fast, Duraliner II, Ufi Gel Hard) to a rapid
      polymerizing denture base resin (QC-20) processed using 2 polymerization cycles
      (A or B), before and after thermal cycling. MATERIALS AND METHODS: Cylinders (3.5
      mm x 5.0 mm) of the reline resins were bonded to cylinders of QC-20 polymerized
      using cycle A (boiling water-20 minutes) or B (boiling water; remove heat-20
      minutes; boiling water-20 minutes). For each reline resin/polymerization cycle
      combination, 10 specimens (groups CAt e CBt) were thermally cycled (5 and 55
      degrees C; dwell time 30 seconds; 2,000 cycles); the other 10 were tested without
      thermal cycling (groups CAwt ad CBwt). Shear bond tests (0.5 mm/min) were
      performed on the specimens and the failure mode was assessed. Data were analyzed
      by 3-way ANOVA and Newman-Keuls post-hoc test (alpha=.05). RESULTS: QC-20 resin
      demonstrated the lowest bond strengths among the reline materials (P<.05) and
      mainly failed cohesively. Overall, the bond strength of the hard chairside reline
      resins were similar (10.09+/-1.40 to 15.17+/-1.73 MPa) and most of the failures
      were adhesive/cohesive (mixed mode). However, Ufi Gel Hard bonded to QC-20
      polymerized using cycle A and not thermally cycled showed the highest bond
      strength (P<.001). When Tokuso Rebase Fast and Duraliner II were bonded to QC-20
      resin polymerized using cycle A, the bond strength was increased (P=.043) after
      thermal cycling. CONCLUSIONS: QC-20 displayed the lowest bond strength values in
      all groups. In general, the bond strengths of the hard chairside reline resins
      were comparable and not affected by polymerization cycle of QC-20 resin and
      thermal cycling.

PMID- 19089245
TI  - The effect of alcohol consumption on periodontal bone support in experimental
      periodontitis in rats.
AB  - OBJECTIVE: The aim of this study was to evaluate the effect of the alcohol
      consumption on the periodontal bone support (PBS) in experimental periodontitis
      in rats. MATERIALS AND METHODS: Sixty-three male rats were divided into seven
      groups: G1 (control); G2 (10% ethanol); G3 (nutritional control of G2); G4 (20%
      ethanol); G5 (nutritional control of G4); G6 (30% ethanol) and G7 (nutritional
      control of G6). The groups G3, G5 and G7 received controlled diets with
      equivalent caloric amounts to those consumed in G2, G4 and G6 respectively, with
      the ethanol replaced by sucrose. After anesthesia, ligatures were installed
      around the mandibular first molar, leaving the contralateral teeth unligated.
      After 8 weeks, the rats were killed and their mandibles were radiographed to
      measure the percentage of PBS on the distal aspect. RESULTS: The intragroup
      analyses showed that presence of ligatures induced periodontitis (p<0.05).
      Unligated groups did not show significant differences among the percentages of
      PBS (p=0.1969). However, in ligated groups the rats that received alcohol
      (G2:48.71%+/-3.88; G4:47.66%+/-2.54; G6:47.32%+/-3.24) and the nutritional
      control group associated with a high concentration of ethanol (G7:47.40%+/-3.24)
      presented a significantly lower percentage of PBS than the other groups
      (G1:52.40%+/-2.75; G3:52.83%+/-2.41; G5:50.85%+/-4.14). CONCLUSIONS: These
      results demonstrated that alcohol consumption in rats may result in a direct
      effect on alveolar bone loss and increased development of periodontitis. In
      addition, they suggest that heavy caloric consumption of ethanol may also present
      an indirect effect on periodontal tissue as a consequence of malnutrition.

PMID- 19089246
TI  - The influence of gender and bruxism on the human maximum bite force.
AB  - The objective of this research was to evaluate the influence of gender and
      bruxism on the maximum bite force. The concordance for the physical examination
      of bruxism between examiners was also evaluated. One hundred and eighteen
      individuals, from both genders, bruxists and non-bruxists, with an average age of
      24 years, were selected for this purpose. For group establishment, every
      individual was submitted to a specific physical examination for bruxism
      (performed by three different examiners). Subjects were then divided into four
      groups according to gender and the presence of bruxism. The maximum bite force
      was measured using a gnathodynamometer at the first molar area, three times on
      each side, performed twice. The two measurements were made with a 10-day
      interval. The highest value was recorded. The mean maximum bite force was
      statistically higher for males (587.2 N) when compared to females (424.9 N)
      (p<0.05), regardless of the presence of bruxism. The presence of bruxism did not
      influence the bite force (mean maximum bite force value for bruxists: 490.1 N,
      and for non bruxists: 522.1 N) (p>0.05). The concordance between examiners for
      physical examination of bruxism was considered optimal.

PMID- 19089247
TI  - Efficacy of biofilm disclosing agent and of three brushes in the control of
      complete denture cleansing.
AB  - OBJECTIVE: This report evaluated the efficacy of three brushes and one biofilm
      disclosing agent in complete denture cleansing. METHODS: Twenty-seven wearers of
      maxillary dentures were distributed into three groups and received different
      brushes: Oral B40, conventional toothbrush (Oral B); Denture, denture-specific
      brush (Condor); Johnson & Johnson, denture-specific brush (Johnson & Johnson).
      The 60-day experimental period was divided into two techniques: I - brushing
      (brush associated with a paste - Dentu Creme, Dentco) three times a day; II -
      brushing and daily application of 1% neutral red on the denture internal surface.
      Biofilm quantification was carried out weekly and the areas with dye biofilm were
      obtained by means of Image Tool 2.02 software. RESULTS: Biofilm removal was more
      effective during Technique II (Wilcoxon test: p=0.01) for the three groups of
      brushes. When the brushes were compared in Technique I, the Kruskal Wallis test
      indicated statistical difference between Denture X Johnson & Johnson and Denture
      X Oral B40, in which the Denture was more efficient. For Technique II, there was
      no statistical difference between brushes (p>0.05). CONCLUSION: The disclosed
      application promoted more efficacy on biofilm removal, regardless of the brush
      used. Denture (Condor) was more efficient than the other brushes during Technique
      I.

PMID- 19089248
TI  - Evaluation of apical deviation in root canals instrumented with K3 and ProTaper
      systems.
AB  - OBJECTIVES: This study evaluated the apical deviation of curved root canals
      instrumented with K3 and ProTaper systems. MATERIAL AND METHODS: Twenty root
      canals of human maxillary and mandibular first molars were employed, which were
      divided into 2 groups: group A (10 teeth) was instrumented with the K3 system,
      and group B (10 teeth) with the ProTaper system. Evaluation of deviation was
      performed by double radiographic exposure. Radiographs were achieved before and
      after instrumentation, with 0.3-second, thus allowing superimposition of images.
      Three-dimensional computerized tomograph was performed in 3 specimens in each
      group, as an additional means to evaluate the apical deviation. RESULTS: Were
      evaluated by the parametric test Student-Newman-Keuls at 5%, which did not reveal
      significance between groups concerning the apical deviation. The results of
      computerized tomograph images demonstrated that the larger deviation of the root
      canal occurred at the distolingual area for both systems. CONCLUSIONS: Both
      techniques produced a mild apical deviation. Computerized microtomography was
      shown to be accurate for experimental endodontics studies.

PMID- 19089249
TI  - Oral findings in patients with Apert syndrome.
AB  - INTRODUCTION: The Apert syndrome is a rare disorder of autosomal dominant
      inheritance caused by mutations in the FGFR2 gene at locus 10q26; patients with
      this syndrome present severe syndactyly, exophthalmia, ocular hypertelorism and
      hypoplastic midface with Class III malocclusion, besides systemic alterations.
      Most investigations available on the Apert syndrome address the genetic aspect or
      surgical management, with little emphasis on the oral aspects. OBJECTIVE: To
      investigate the oral findings, including dental anomalies, ectopic eruption of
      the maxillary permanent first molars and soft tissue alterations, in subjects
      with Apert syndrome. MATERIALS AND METHODS: Clinical and radiographic examination
      of nine patients with Apert syndrome, aged 6 to 15 years, not previously
      submitted to orthodontic or orthognathic treatment. RESULTS: Dental anomalies
      were present in all patients, with one to eight anomalies per individual. The
      most frequent anomalies were tooth agenesis, mainly affecting maxillary canines,
      and enamel opacities (44.4% for both). Ectopic eruption of maxillary first molars
      was found in 33.3% of patients; lateral palatal swellings were observed in 88.8%
      of patients. CONCLUSIONS: The occurrence of typical lateral palatal swellings
      agrees with the literature. The high prevalence of dental anomalies and ectopic
      eruption may suggest a possible etiologic relationship with the syndrome.

PMID- 19089250
TI  - Long-term stability of an anterior open-bite malocclusion treated in the mixed
      dentition: a case report.
AB  - A clinical case with anterior open-bite, treated in the mixed dentition, is
      presented. This approach demonstrates one of the possible approaches of
      treatment, which is capable of interfering with growth and redirecting its
      vectors. Orthodontic and orthopedic methods were used, consisting of slow
      maxillary expansion, through a fixed palatal crib soldered in a bi-helix
      appliance, and high-pull traction on the mandible for 16 hours a day. After eight
      years of follow-up, stable outcomes were accomplished. These results may be
      explained by the fact that treatments were performed at the appropriate period of
      development, thus establishing perioral muscular equilibrium, matching the final
      period of facial growth. The combination of orthodontic and orthopedic treatments
      was necessary to prevent the need of further orthognathic surgery treatment.

PMID- 19089251
TI  - Vestibular schwannoma (acoustic neuroma) mimicking temporomandibular disorders: a
      case report.
AB  - Approximately 6 to 16% of patients with trigeminal neuralgia symptoms present
      intracranial tumors, the most common being the vestibular schwannoma (acoustic
      neuroma). Some symptoms reported by patients include hearing loss, tinnitus,
      headaches, vertigo and trigeminal disturbances. An increased muscle response in
      the surrounding head and neck musculature may also be observed, which mimics
      signs and symptoms of temporomandibular disorders. In these cases, magnetic
      resonance imaging (MRI) has proved to be a useful tool in tumor diagnosis. The
      differential diagnosis between myofascial and neuralgic pain is important, as
      both may present similar characteristics, while being of different origin, and
      demanding special treatment approaches. The purpose of this paper is to
      demonstrate the relationship among trigeminal neuralgia symptoms, intracranial
      tumors and temporomandibular dysfunction by presenting a clinical case.

PMID- 19089253
TI  - Letter to editor.

PMID- 19089255
TI  - Incidence and anatomic localization of oral candidiasis in patients with AIDS
      hospitalized in a public hospital in Belo Horizonte, MG, Brazil.
AB  - The objective of this study was to evaluate the incidence, anatomic localization
      and yeast species isolated from each clinical type of oral candidiasis. The
      clinical samples were obtained from 67 patients with AIDS with CD4 cell counts
      below 200 cells/mm(3) and hospitalized in a public hospital (Eduardo de Menezes
      Hospital) in the city of Belo Horizonte, MG, Brazil. Yeasts were isolated using
      Chromagar Candida. The results show that 50.7% of these patients had oral
      candidiasis. The pseudomembranous form was the most frequent clinical
      manifestation of oral candidiasis, followed by the erythematous and angular
      cheilite forms. The most common site of these clinical forms of oral candidiasis
      was the tongue. Candida albicans was the most common yeast species isolated from
      the lesions. However, other species were also found to be associated with these
      forms of oral candidiasis.

PMID- 19089254
TI  - Slow-release fluoride devices: a literature review.
AB  - Although the prevalence of caries has decreased dramatically over the past
      decades, it has become a polarised disease, with most of subjects presenting low
      caries levels and few individuals accounting for most of the caries affected
      surfaces. Thus it become evident for the need of clinical approaches directed at
      these high-risk patients, in order to overcome problems related to compliance and
      low attendance at dental care centres. Slow-release fluoride devices were
      developed based on the inverse relationship existing between intra-oral fluoride
      levels and dental caries experience. The two main types of slow-release devices -
      copolymer membrane type and glass bead - are addressed in the present review. A
      substantial number of studies have demonstrated that these devices are effective
      in raising intra-oral F concentrations at levels able to reduce enamel
      solubility, resulting in a caries-protective effect. Studies in animals and
      humans demonstrated that the use of these devices was able to also protect the
      occlusal surfaces, not normally protected by conventional fluoride regimens.
      However, retention rates have been shown to be the main problem related to these
      devices and still requires further improvements. Although the results of these
      studies are very promising, further randomised clinical trials are needed in
      order to validate the use of these devices in clinical practice. The concept of
      continuously providing low levels of intra-oral fluoride has great potential for
      caries prevention in high caries-risk groups.

PMID- 19089256
TI  - Histometric analysis of ligature-induced periodontitis in rats: a comparison of
      histological section planes.
AB  - The purpose of this study was to analyze the histometry of ligature-induced
      periodontitis in rats at different histological section depths. Sixteen male
      adult Wistar rats were randomly assigned to two groups: ligature and control. In
      the ligature group, rats received a sterile 4/0 silk ligature around the
      maxillary right 2nd molar. Thirty serial sections containing the 1st and 2nd
      molars, in which the coronal and root pulp, cementoenamel junction (CEJ) in the
      mesial side of the 2nd molar, interproximal alveolar bone and connective fiber
      attachment were clearly visible, were selected for histometric analysis. The
      histological sections were clustered in groups of 10 sections corresponding the
      buccal (B), central (C) and lingual (L) regions of the of periodontal tissue
      samples. The distance between the CEJ in the mesial side of the 2nd molar and the
      attached periodontal ligament fibers (CEJ-PL) as well as the distance between the
      CEJ and the alveolar bone crest (CEJ-BC) were determined. From CEJ-PL and CEJ-BC
      distances measured for each specimen, the measurements obtained in the B, L and C
      regions were recorded individually and together. Data were submitted to
      statistical analysis. Significant differences (p<0.001) were observed between the
      control and ligature groups regarding CEJ-PL (0.05 mm and 0.26 mm, respectively)
      and CEJ-BC (0.47 mm and 0.77 mm, respectively) measurements. Regarding the depth
      of the buccal, central and lingual planes, the means of CEJ-PL and CEJ-BC of both
      groups showed no statistically significant differences (p>0.05). In conclusion,
      the selection of 10 serial sections of the central region of periodontal tissue
      samples at any depth can be considered as representative for the evaluation of
      periodontal ligament fiber attachment and bone loss in ligature-induced
      periodontitis in rats.

PMID- 19089257
TI  - Surface degradation of composite resins by acidic medicines and pH-cycling.
AB  - This study evaluated the effects of acidic medicines (Dimetapp and Claritin),
      under pH-cycling conditions, on the surface degradation of four composite resins
      (microhybrid: TPH, Concept, Opallis and Nanofilled: Supreme). Thirty disc-shaped
      specimens ([symbol: see text] = 5.0 mm/thickness = 2.0 mm) of each composite were
      randomly assigned to 3 groups (n = 10): a control and two experimental groups,
      according to the acidic medicines evaluated. The specimens were finished and
      polished with aluminum oxide discs, and the surface roughness was measured by
      using a profilometer. After the specimens were submitted to a pH-cycling regimen
      and immersion in acidic medicines for 12 days, the surface roughness was measured
      again. Two specimens for each material and group were analyzed by scanning
      electron microscopy (SEM) before and after pH-cycling. Data were analyzed by the
      Student's-t test, ANOVA, Duncan's multiple range test and paired t-test
      (alpha=0.05). Significant increase in roughness was found only for TPH in the
      control group and TPH and Supreme immersed in Claritin (p<0.05). SEM analyses
      showed that the 4 composite resins underwent erosion and surface degradation
      after being subjected to the experimental conditions. In conclusion, although the
      roughness was slightly affected, the pH-cycling and acidic medicines caused
      surface degradation of the composite resins evaluated. Titratable acidity seemed
      to play a more crucial role on surface degradation of composite resins than pH.

PMID- 19089258
TI  - Influence of the curing method on the post-polymerization shrinkage stress of a
      composite resin.
AB  - The aim of this study was to evaluate the effect of different curing methods on
      the stress generated by the polymerization shrinkage of a restorative composite
      in two moments: immediately after light exposure and after 5 min. Photoactivation
      was performed using two different light sources: (1) xenon plasma arc (PAC) light
      (1,500 mW/cm2 - 3s) and (2) a quartz-tungsten-halogen (QTH) light with three
      light-curing regimens: continuous exposure (40 s at 800 mW/cm2 - CL); soft-start
      (10 s at 150 mW/cm2 and 30 s at 800 mW/cm2 - SS) and intermittent light [cycles
      of 4 s (2 s with light on at 600 mW/cm2 and 2 s of light off), for 80s - IL]. The
      composite resin was applied between two 5-mm diameter metallic rods, mounted in a
      servohydraulic machine. The maximum stress was recorded immediately after light
      exposure (FF) and after 5 min (5F). The results were submitted to ANOVA and
      Tukey's test (5%). For each method, the results obtained in FF and 5F were,
      respectively: CL (3.58 and 4.46 MPa); SS (2.99 and 4.36 MPa); IL (3.11 and 4.32
      MPa) and PAC (0.72 and 3.27 MPa). The stress generated by the polymerization
      shrinkage during light exposure can be associated with the photoactivation method
      used. A significant increase in the stress level was observed during the post
      curing period up to 5 min, for all evaluated methods.

PMID- 19089259
TI  - Effectiveness of a new toothbrush design versus a conventional tongue scraper in
      improving breath odor and reducing tongue microbiota.
AB  - For centuries, specific instruments or regular toothbrushes have routinely been
      used to remove tongue biofilm and improve breath odor. Toothbrushes with a tongue
      scraper on the back of their head have recently been introduced to the market.
      The present study compared the effectiveness of a manual toothbrush with this new
      design, i.e., possessing a tongue scraper, and a commercial tongue scraper in
      improving breath odor and reducing the aerobic and anaerobic microbiota of tongue
      surface. The evaluations occurred at 4 moments, when the participants (n=30) had
      their halitosis quantified with a halimeter and scored according to a 4-point
      scoring system corresponding to different levels of intensity. Saliva was
      collected for counts of aerobic and anaerobic microorganisms. Data were analyzed
      statistically by Friedman's test (p<0.05). When differences were detected, the
      Wilcoxon test adjusted for Bonferroni correction was used for multiple
      comparisons (group to group). The results confirmed the importance of mechanical
      cleaning of the tongue, since this procedure provided an improvement in halitosis
      and reduction of aerobe and anaerobe counts. Regarding the evaluated methods, the
      toothbrush's tongue scraper and conventional tongue scraper had a similar
      performance in terms of breath improvement and reduction of tongue microbiota,
      and may be indicated as effective methods for tongue cleaning.

PMID- 19089260
TI  - Determination of the maximum inhibitory dilution of cetylpyridinium chloride
      based mouthwashes against Staphylococcus aureus: an in vitro study.
AB  - The aim of this in vitro study was to determine the maximum inhibitory dilution
      (MID) of four cetylpyridinium chloride (CPC)-based mouthwashes: CPC+Propolis,
      CPC+Malva, CPC+Eucaliptol+Jua+Roma+Propolis (Natural Honey) and CPC (Cepacol),
      against 28 Staphylococcus aureus field strains, using the agar dilution method.
      Decimal dilutions ranging from 1/10 to 1/655,360 were prepared and added to
      Mueller Hinton Agar. Strains were inoculated using Steers multipoint inoculator.
      The inocula were seeded onto the surface of the culture medium in Petri dishes
      containing different dilutions of the mouthwashes. The dishes were incubated at
      37 degrees C for 24 h. For readings, the MID was considered as the maximum
      dilution of mouthwash still capable of inhibiting microbial growth. The obtained
      data showed that CPC+Propolis had antimicrobial activity against 27 strains at
      1/320 dilution and against all 28 strains at 1/160 dilution, CPC+Malva inhibited
      the growth of all 28 strains at 1/320 dilution, CPC+Eucaliptol+Jua+Roma+Propolis
      inhibited the growth of 2 strains at 1/640 dilution and all 28 strains at 1/320
      dilution, and Cepacol showed antimicrobial activity against 3 strains at 1/320
      dilution and against all 28 strains at 1/160 dilution. Data were submitted to
      Kruskal-Wallis test, showing that the MID of Cepacol was lower than that
      determined for the other products (p<0.05). In conclusion, CPC-mouthwashes showed
      antimicrobial activity against S. aureus and the addition of other substances to
      CPC improved its antimicrobial effect.

PMID- 19089261
TI  - Effect of conventional and experimental gingival retraction solutions on the
      tensile strength and inhibition of polymerization of four types of impression
      materials.
AB  - In the present study, two types of tests (tensile strength test and
      polymerization inhibition test) were performed to evaluate the physical and
      chemical properties of four impression materials [a polysulfide (Permlastic), a
      polyether (Impregum), a condensation silicone (Xantopren) and a polyvinylsiloxane
      (Aquasil)] when polymerized in contact with of one conventional (Hemostop) and
      two experimental (Vislin and Afrin) gingival retraction solutions. For the
      tensile strength test, the impression materials were mixed and packed into a
      steel plate with perforations that had residues of the gingival retraction
      solutions. After polymerization, the specimens were tested in tensile strength in
      a universal testing machine. For the polymerization inhibition test, specimens
      were obtained after taking impressions from a matrix with perforations that
      contained 1 drop of the gingival retraction solutions. Two independent examiners
      decided on whether or not impression material remnants remained unpolymerized,
      indicating interference of the chemical solutions. Based on the analysis of the
      results of both tests, the following conclusions were reached: 1. The tensile
      strength of the polysulfide decreased after contact with Hemostop and Afrin. 2.
      None of the chemical solutions inhibited the polymerization of the polysulfide;
      3. The polyether presented lower tensile strength after polymerization in contact
      with the three gingival retraction agents; 4. The polyether had its
      polymerization inhibited only by Hemostop; 5. None of the chemical solutions
      affected the tensile strength of the condensation silicone; 6. Only Hemostop
      inhibited the polymerization of the condensation silicone; 7. The
      polyvinylsiloxane specimens polymerized in contact with Hemostop had
      significantly lower tensile strength; 8. Neither of the chemical solutions (Afrin
      and Vislin) affected the tensile strength of the polyvinylsiloxane and the
      condensation silicone; 9. Results of the tensile strength and polymerization
      inhibition tests suggest that Vislin can be used as substance of gingival
      retraction without affecting the tested properties of four impression materials.

PMID- 19089262
TI  - Dental caries experience in 12-year-old schoolchildren in southeastern Brazil.
AB  - The aim of this study was to evaluate the prevalence of caries-free children
      using DMFT and significant caries (SiC) indexes in different caries prevalence
      groups in cities of the region of Campinas, Sao Paulo State, Brazil. The
      methodology proposed by the World Health Organization (1997) was used for caries
      diagnosis in 2,378 individuals. According to the DMFT index obtained in each
      evaluated city, 3 prevalence groups with representative samples were formed,
      being classified as low, moderate and high. SiC index was used to classify the
      one third of the population with the highest caries prevalence. In the low
      prevalence group, 32.4% of the children were caries free (DMFT=0), with mean DMFT
      of 2.29 and SiC index of 4.93. In the moderate prevalence group, 21.8% of the
      children were caries free, with mean DMFT of 3.36 and SiC of 6.74. Only 6.9% of
      the children in the high prevalence group were caries free and the mean DMFT was
      5.54 (SiC=9.62). There was a great heterogeneity in dental caries distribution
      within the studied population, as well as a high caries prevalence considering
      the 3 classifications. Other indexes besides DMFT could be used to improve oral
      health assessment during establishment of the treatment plan and intervention.

PMID- 19089263
TI  - Effect of a dentifrice containing Aloe vera on plaque and gingivitis control. A
      double-blind clinical study in humans.
AB  - The effect of Aloe vera on the reduction of plaque and gingivitis was evaluated
      in a randomized, parallel and double-blind clinical trial. Subjects were randomly
      allocated to the test group (n=15) - dentifrice containing Aloe vera - or the
      control group (n=15) - fluoridated dentifrice. Plaque index (PI) and gingival
      bleeding index (GBI) were assessed at days 0 and 30. Subjects were asked to brush
      their teeth with the control or test dentifrice, three times a day, during a 30
      day period. There was a significant reduction on plaque and gingivitis in both
      groups, but no statistically significant difference was observed among them
      (p>0.01). The dentifrice containing Aloe vera did not show any additional effect
      on plaque and gingivitis control compared to the fluoridated dentifrice.

PMID- 19089265
TI  - Segmental LeFort I osteotomy for treatment of a Class III malocclusion with
      temporomandibular disorder.
AB  - This article reports the case of a 19-year-old young man with Class III
      malocclusion and posterior crossbite with concerns about temporomandibular
      disorder (TMD), esthetics and functional problems. Surgical-orthodontic treatment
      was carried out by decompensation of the mandibular incisors and segmentation of
      the maxilla in 4 pieces, which allowed expansion and advancement. Remission of
      the signs and symptoms occurred after surgical-orthodontic intervention. The
      maxillary dental arch presented normal transverse dimension. Satisfactory static
      and functional occlusion and esthetic results were achieved and remained stable.
      Three years after the surgical-orthodontic treatment, no TMD sign or symptom was
      observed and the occlusal results had not changed. When vertical or horizontal
      movements of the maxilla in the presence of moderate maxillary constriction are
      necessary, segmental LeFort I osteotomy can be an important part of treatment
      planning.

PMID- 19089264
TI  - Toxicity testing of restorative dental materials using brine shrimp larvae
      (Artemia salina).
AB  - This study investigated the effect of extracts of different composites, glass
      ionomer cement (GIC)s and compomers on the viability of brine shrimp larvae.
      Ethanolic extracts of four dental composites (Z-100; Solitaire 2; Filtek P60 and
      Synergy), a conventional GIC (Ketac-Fil), a resin-modified glass ionomer cement
      (Vitremer), two compomers (F2000; Dyract AP), and a flowable compomer (Dyract
      Flow) were prepared from each material. Following evaporation of the ethanol, the
      extracts were resuspended in distilled water, which was then used to test the
      effects on the viability of brine shrimp larvae. For the composites, the extract
      of Synergy was the least toxic (88% viability) followed by the extracts of
      Solitaire 2, Z100 and P60 (75%, 67.5% and 50% viability, respectively). One-way
      ANOVA revealed highly significant differences between the resin composite
      materials (p<0.001). Follow-up comparison between the composite groups by Tukey's
      pairwise multiple-comparison test (alpha =0.05) showed that the extract of
      Synergy was significantly less toxic than the extracts of all the other materials
      except that of Solitaire 2. The compomers showed 100% lethality, while the
      percentage of viable larvae for the extracts of Ketac-Fil, and Vitremer were
      32.3%, and 37.0%, respectively. One-way ANOVA revealed highly significant
      differences between the groups of materials (p<0.001). Follow-up comparison
      between the groups by Tukey's test (alpha = 0.05) showed that the toxic effect of
      the extracts of the compomers were significantly greater than that of Ketac-Fil,
      and Vitremer. The differences in the toxic effects of Vitremer and Ketac-Fil were
      not statistically significant. In conclusion, the toxicity of composite materials
      varied according to their chemical composition. Compomers were the most lethal
      materials to brine shrimp larvae followed by GICs and then composites.

PMID- 19089266
TI  - Sealing ability of cements in root canals prepared for intraradicular posts.
AB  - This research evaluated the sealer ability of 2 temporary filling materials
      (white Cimpat and IRM) and 1 restorative cement (glass ionomer), in canals
      prepared for root posts. Sixty human palatal roots of maxillary first molars were
      used. They were divided into 3 groups, according to the cements used: Group I
      (Cimpat), Group II (IRM) and Group III (glass ionomer). The roots were rendered
      impermeable, filled with the respective cements and soon after immersed into 0.2%
      Rhodamine B dye and maintained for 72 hours in an oven for 37 degrees C.
      Microleakage was measured with a light microscope, cutting the roots
      longitudinally in buccolingual direction. The results showed that Group I
      presented significantly more leakage than Groups II and III, which were not
      significantly different from each other.

PMID- 19089267
TI  - The influence of gestational age and birth weight of the newborn on tooth
      eruption.
AB  - OBJECTIVE: The aim of the present study was to compare the beginning of eruption
      of the first deciduous tooth in preterm infants (<38 weeks) with full-term
      infants (38 and 42 weeks) of normal birth weight ((3)2.500g), low birth weight (<
      2.500g) and very low birth weight (<1.500g), in order to evaluate if premature
      birth and low birth weight would affect tooth eruption. METHODS: The neonatal
      records and the moment of eruption of the first deciduous tooth of 146 infants -
      77 preterm infants and 69 full-term infants, ranging from 5 to 36 months old, of
      both genders - were recorded. All of them were under care at the Pediatric
      Ambulatory of Hospital Universitario Evangelico at Curitiba - Parana. Data were
      analyzed considering biological age and post-conception, or corrected, age -
      which is the gestational age plus the infant's chronological age at the month of
      eruption of the first deciduous tooth. RESULTS: Results showed that when
      chronological age is considered, tooth eruption in preterm and very low birth
      weight infants is importantly delayed. However, when corrected age is considered,
      no statistically significant differences were found among groups. CONCLUSION: The
      delayed eruption may be related to the premature birth and not to a delay in
      dental development.

PMID- 19089268
TI  - Anticariogenic potencial of acidulate solutions with low fluoride concentration.
AB  - OBJECTIVES: The aim of this study was to verify the anticariogenic effect of
      acidulate solutions with low NaF concentration, using pH-cycling model and bovine
      enamel. MATERIAL AND METHODS: Enamel blocks were submitted to the surface
      microhardness (SMH) test and randomly divided in 12 experimental and one placebo
      groups. The blocks were submitted to pH cycling for 7 days, with daily
      applications once/day of 0.05% NaF and 0.1% NaF and twice/day of 0.02% NaF
      solutions. Four different pH: 4.0, 5.0, 6.0 and 7.0 were used. Next, SMH test was
      again used to determine the surface microhardness percentage change (%SMH). Data
      obtained for %SMH were homogeneous and passed through variance analyses and
      Tukey's test (5%) as far as fluoride concentrations and pH. RESULTS: The results
      showed that pH influenced %SMH in 0.02% NaF and 0.05% NaF solutions with pH 4.0,
      which had less mineral loss compared to pH 7.0 (p<0.05). The 0.02% NaF - pH 4.0,
      and 0.05% NaF - pH 7.0 groups showed similar results (p>0.05). A dose-response
      relationship was observed among the tested solutions, with better anticariogenic
      effect for the 0.1% NaF solution. CONCLUSION: The results suggest that the
      addition of citric acid to acidulate mouth rinses reduce mineral loss.

PMID- 19089269
TI  - Plasma as an indicator of bone fluoride levels in rats chronically exposed to
      fluoride.
AB  - OBJECTIVE: This study evaluated the use of plasma, bone surface (periosteal) and
      whole bone as biomarkers of chronic fluoride (F) exposure. METHODS: Forty male
      Wistar rats were assigned to 4 groups (n=10/gr) that differed according to the F
      concentration they received in the drinking water. Groups 1, 2, 3 and 4 received
      water containing 0 (control), 5, 15, and 50 mg F/L, respectively. The rats were
      killed at 120 days of age. Plasma and femur were collected and analyzed for
      fluoride with the ion specific electrode by the direct method or after
      hexamethyldisiloxane-facilitated diffusion. Data were tested for statistically
      significant differences by ANOVA and linear regression (p<0.05). RESULTS: Mean
      (+/- SE) plasma F concentrations ranged from 0.030 +/- 0.002 to 0.187 +/- 0.013
      (mg/mL). The concentrations in surface and whole bone ranged from 610 +/- 32 to
      4,693 222; and 647 +/- 22 to 3,439 +/- 134 microg/g, respectively. The
      surface/whole F concentration ratios were 0.941, 1.414, 1.173 and 1.377, for
      groups 1, 2, 3 and 4 respectively. For plasma and whole bone, the difference
      among all groups was statistically significant, except for group 2 compared to
      group 1. For bone surface, all groups differed from each other except for group 2
      compared to group 3. A significant positive correlation was found between bone
      surface and whole bone F (r(2)=0.94), as well as between plasma and bone surface
      (r(2)=0.71) and plasma and whole bone (r(2)=0.74). CONCLUSIONS: Data suggest that
      both bone surface and whole bone are suitable biomarkers of chronic F exposure in
      rats and plasma may be used as indicator of bone fluoride levels.

PMID- 19089270
TI  - Weight loss of five commercially available denture teeth after toothbrushing with
      three different dentifrices.
AB  - Brushing is the most common cleansing method employed on complete dentures and it
      may damage the integrity of acrylic resin, the main component of this type of
      prosthesis. This study evaluated the abrasion resistance of artificial teeth with
      different number of acrylic layers, and the abrasiveness of specific and non
      specific dentifrices for denture cleaning. The abrasion test was conducted by a
      tooth brushing device, using soft toothbrushes under load (200g). Sixty
      artificial teeth specimens were manufactured, 12 from each brand: Vipi-Dent Plus
      (Dental Vipi), Trubyte Biotone (Dentsply), Trilux (Ruthinium), Ivostar (Ivoclar)
      and SR Vivodent PE (Ivoclar). Three brands of dentifrices were selected: Colgate
      (Colgate-Palmolive), Bonyplus (Bonyf AG) and Dentu-Creme (Dentco). Distilled
      water was used as control. The brushing time was 100 minutes, at 356
      strokes/minute. The specimens were weighed on an analytical balance before and
      after the abrasion test. Analysis of dentifrices' abrasive particles was made by
      scanning electron microscopy (SEM). Two-way ANOVA and Tukey tests were employed
      (alpha=0.05). The general mean of weight loss values were obtained: 6.1 mg
      (Ivostar); 6.0 mg (Trilux); 5.9 mg (Trubyte); 5.8 mg (Vipi); 5.3 mg (Vivodent).
      The abrasiveness difference among teeth brands was not statistically significant.
      The Colgate dentifrice produced the greatest weight reduction (10.1 mg), followed
      by Dentu-Creme (7.6 mg). Bonyplus was the least abrasive (2.4 mg), similar to the
      distilled water used as control group (3.1 mg) (p=0.05). It was concluded that
      all acrylic teeth presented similar abrasion resistance. Specific dentifrices for
      dentures tend to cause less damage to acrylic resin.

PMID- 19089271
TI  - Fracture resistance and failure pattern of teeth submitted to internal bleaching
      with 37% carbamide peroxide, with application of different restorative
      procedures.
AB  - OBJECTIVE: This study investigated the compressive fracture strength and failure
      pattern in premolars submitted to endodontic treatment and internal bleaching
      with 37% carbamide peroxide for 21 days, with application of different
      restorative procedures. MATERIAL AND METHODS: Six groups were employed (n = 10):
      1) non-bleached teeth and pulp chamber sealed with IRM; 2) bleached teeth and
      pulp chamber sealed with IRM; 3) bleached teeth and pulp chamber filled with
      light cured composite resin; 4) bleached teeth, root canals prepared at 10mm,
      filling of the root canal and pulp chamber with IRM; 5) bleached teeth, root
      canals prepared at 10mm, luting of prefabricated metallic post with zinc
      phosphate and pulp chamber sealed with composite resin; 6) bleached teeth, root
      canals prepared at 10mm, luting of glass fiber post with resin cement and pulp
      chamber sealed with composite resin. After 24-hour storage in distilled water,
      the specimens were submitted to compressive fracture strength testing in a
      universal testing machine. RESULTS: The following values were found: Group 1 -
      56.23kgf; Group 2 - 48.96kgf; Group 3 - 53.99kgf; Group 4 - 45.72kgf; Group 5 -
      54.22kgf; Group 6 - 60.12kgf. The analysis of variance did not reveal
      statistically significant difference between groups (p<0.05), suggesting that
      internal bleaching with 37% carbamide peroxide did not weaken the dental tissues.
      The largest number of unfavorable fractures was observed for Groups 2 (50%), 4
      (40%), and 5 (30%). Group 6 exhibited the most favorable failure pattern.
      CONCLUSIONS: The results suggest that internal bleaching with 37% carbamide
      peroxide did not significantly weaken the teeth. Among the bleached teeth, those
      with temporary IRM restorations or metallic posts demonstrated the most
      unfavorable fracture pattern, whereas the most favorable fracture pattern
      occurred in teeth restored with composite resin and glass fiber posts.

PMID- 19089272
TI  - Dental mineralization and salivary activity are reduced in offspring of
      spontaneously hypertensive rats (SHR).
AB  - Several pathologies have been diagnosed in children of hypertensive mothers;
      however, some studies that evaluated the alterations in their oral health are not
      conclusive. This study analyzed the salivary gland activity and dental
      mineralization of offsprings of spontaneously hypertensive rats (SHR). Thirty-day
      old SHR males and Wistar rats were studied. The salivary flow was evaluated by
      injection of pilocarpine, the protein concentration and salivary amylase
      activity, by the Lowry method and kinetic method at 405 nm, respectively. Enamel
      and dentin mineralization of the mandibular incisors was quantified with aid of
      the microhardness meter. The results were analyzed by the ANOVA or Student's t
      test (p<0.05). It was noticed that the salivary flow rate (0.026 mL/min/100 g +/-
      0.002) and salivary protein concentration (2.26 mg/mL +/- 0.14) of SHR offspring
      were reduced compared to Wistar normotensive offspring (0.036 mL/min/100 g +/-
      0.003 and 2.91 mg/mL +/- 0.27, respectively), yet there was no alteration in
      amylase activity (SHR: 242.4 U/mL +/- 36.9; Wistar: 163.8 U/mL +/- 14.1).
      Microhardness was lower both in enamel (255.8 KHN +/- 2.6) and dentin (59.9 KHN
      +/- 0.8) for the SHR teeth compared to the Wistar teeth (enamel: 328.7 KHN +/-
      3.3 and dentin: 67.1 KHN +/- 1.0). These results suggest that the SHR offspring
      are more susceptible to development of pathologies impairing oral health, once
      they presented lesser flow and salivary protein concentration and lower dental
      mineralization.

PMID- 19089273
TI  - In vitro study of the effect of Er:YAG laser irradiation on the apical sealing of
      different root canal sealers.
AB  - OBJECTIVES: The aim of this study was to determine the effect of Er:YAG laser
      irradiation used to clean dentinal walls on the apical sealing of root canals
      filled with different types of sealers. BACKGROUND DATA: Laser application to the
      dentinal walls removed debris, rendering the root canals free of smear layers and
      leaving the dentinal canaliculi open. METHODS: Sixty-four maxillary canines
      obtained from laboratory files were instrumented with K-files (Dentsply,
      Maillefer, Ballaigues, Switzerland) using the crown-down technique, and irrigated
      with a 0.5% sodium hypochlorite solution. The specimens were divided into two
      groups of 32 teeth each. In group I, the teeth were instrumented and irrigated
      with sodium hypochlorite solution, and divided into four subgroups to be sealed
      with the different materials (Endofill, N-Rickert, Sealapex and Sealer 26). In
      group II, the root canals were subjected to Er:YAG laser irradiation (200 mJ, 7
      Hz and 60 J total energy), followed by root canal sealing as in group I. RESULTS:
      The data showed lower levels of apical microleakage in the teeth filled with N
      Rickert, Sealapex and Sealer 26 cements than in those sealed with Endofill (p <
      0.01). No significant difference in microleakage was observed between teeth
      irrigated only with 0.5% sodium hypochlorite and those submitted to Er:YAG laser
      application (p > 0.05). CONCLUSIONS: The Er:YAG laser irradiation applied to the
      root canal walls was not able to prevent apical microleakage.

PMID- 19089274
TI  - Mouth floor enlargements related to the sublingual glands in edentulous or
      partially edentulous patients: a microscopic study.
AB  - Mouth floor enlargements (MFE) are observed in edentulous and partially
      edentulous patients, impairing denture fitting, and have recently been described
      in the literature as hyperplasias of the sublingual glands. OBJECTIVE: This study
      aims at describing the microscopic aspects of MFE that contribute to their final
      diagnosis. METHODS: Twenty-four specimens were surgically removed from the
      enlarged mouth floor of 19 patients (15 females and 4 males). Patient age ranged
      from 48 to 74 years, with a mean of 57 years. The main surgical indication was to
      permit or improve the fitting of dentures. Six patients were completely
      edentulous and 13 were partially edentulous. The material was processed for
      microscopic examination and stained with hematoxylin-eosin, Mallory's trichrome
      and periodic-acid Schiff (PAS). RESULTS AND CONCLUSIONS: The epithelium of the
      mouth floor was normal in 17 cases, hyperplastic in 4 and atrophic in 3. Six of
      the 24 sublingual glands removed were microscopically normal, while the other
      specimens presented acinar atrophy with hyperplasia of duct-like structures.
      Interstitial fibrosis was observed in 18 cases and was accompanied by adipose
      tissue infiltration in 15. Decreased lymphoid tissue was observed in 16 samples
      and oncocytosis was present in 5 cases. We suggest that MFE in edentulous or
      partially edentulous patients should be considered as an entity for the text
      books.

PMID- 19089275
TI  - Evaluation of glass ionomer sealants placed according to the ART approach in a
      community with high caries experience: 1-year follow-up.
AB  - The aim of this study was to investigate the retention rates and effect on
      occlusal caries incidence of two glass ionomers used as sealants, placed
      according to the Atraumatic Restorative Treatment (ART) approach, in a high
      caries-risk community. A total of 150 newly erupted first molars of 42
      schoolchildren, between 6-8 years of age were selected. The teeth were divided
      into two groups: experimental and control groups. In the experimental group, 76
      teeth were sealed using Vidrion R-SS White (conventional GIC) and in the control
      group, 74 teeth were sealed using ChemFlex-Dentsply (high-viscosity conventional
      GIC). The sealants were applied by one operator following the "press finger
      technique", described in the ART-WHO manual. Two calibrated independent examiners
      carried out the evaluation according to the ART criteria. The intra and inter
      examiner agreements were 0.84 and 0.81, respectively. Data were submitted to Mann
      Whitney and Chi-square tests (p<0.05). At the 1-year follow-up, 136 (90.7%)
      sealants were evaluated. In the control group: 28 (41.8%) of the sealants were
      partially or completely retained, 38 (56.7%) completely lost, and 1 (1.5%) was
      replaced by another treatment. In the experimental group, 30 (43.5%) of the
      sealants were partially or completely retained, 38 (55.1%) were clinically scored
      as complete loss and 1 (1.4%) were replaced by another treatment. Seven sealants
      in both groups were not evaluated. Secondary caries was not observed in both
      groups. There was no statistically significant difference between the retention
      (p=0.49) and effect on caries incidence rates for both groups (p=0.84). The
      clinical performance of the glass ionomer sealants of both groups was considered
      satisfactory with a high success rate (98.5%). Although the sealants placed
      according to the ART approach showed retention rates lower than 50% after 1 year
      in newly erupted first molars, this approach seems to be appropriate for
      communities with high caries experience.

PMID- 19089276
TI  - PCNA and p53 expression in oral leukoplakia with different degrees of
      keratinization.
AB  - Leukoplakias are oral lesions that may have many clinical and histological
      aspects and they are usually associated with malignancy when dysplastic
      alterations are shown. However, these transformations may occur in non-dysplastic
      lesions that show harmless clinical aspect. For this reason, the proposal was to
      study the p53 and PCNA immunohistochemical expression in non-dysplastic
      leukoplakias, trying to correlate the results only with the epithelial
      keratinization degree. For this, 24 leukoplakias degrees I, II and III of
      Grinspan were used, all of them located in oral mucosa. Most of the leukoplakias
      showed p53 and PCNA expression in their different keratinization degrees. The p53
      marking was confined to the basal and parabasal layers, while the PCNA marking
      occurred in practically all epithelial layers. The expression pattern of these
      markers was histologically and statistically similar between the lesions with
      these keratinization variations. It was evident that non-dysplastic epithelium of
      leukoplakias showed submicroscopical signs of alterations that lead to malignant
      transformation, and that the keratinization degree did not correlate to a greater
      risk of this event.

PMID- 19089277
TI  - Evaluation of the need to distinguish between white and black patients in
      predicting the combined mesiodistal crown width of canines and premolars.
AB  - The aim of the present study was to evaluate the need to distinguish between
      white and black patients when predicting the combined mesiodistal crown width of
      canines and premolars in Recife. A sample of 120 dental casts (60 from black and
      60 from white patients) was selected from the archives of dental clinics in
      Recife. The mesiodistal crown width of the maxillary and mandibular canines and
      premolars and of the mandibular incisors was measured in these casts using a
      caliper with an accuracy of 0.02mm. The combined mesiodistal crown width of these
      teeth in the black patients was compared with that found in the white patients,
      and also with the estimated values obtained by regression equations based on the
      sample of white patients and on a large sample of a population from the same
      city. The study demonstrated that there were no significant differences between
      whites and blacks in the combined mesiodistal crown width of any of the three
      analyzed teeth groups and also revealed that such equations were statistically
      accurate in estimating the mesiodistal crown width of canines and premolars in
      blacks. It was concluded that there is no need for specific tables or equations
      regarding the patient's race in the analysis of mixed dentition in Recife.

PMID- 19089278
TI  - The compatibility of denture cleansers and resilient liners.
AB  - PURPOSE: Difficulty in cleaning resilient denture liners remains a material
      disadvantage. The purpose of the present study was to evaluate the effect of
      denture cleansers on hardness of resilient liner materials. MATERIALS AND
      METHODS: Three resilient liners, Luci Sof (Dentsply), Molloplast-B (Dentax), and
      Sofreliner (Tokuyama), and two denture cleansers, Efferdent (Warner-Lamber), and
      0.5% alkaline hypochlorite preparation were used. Twenty specimens of each
      material were prepared, measuring 25X15X3mm. Two denture cleansing approaches
      were used: 1) alkaline hypochlorite, for 20 minutes; 2) alkaline peroxide, for 30
      minutes. This procedure was repeated 8 times a day, during 90 days. The specimens
      were evaluated before and after 360 and 720 cycles, to simulate 1 and 2 years of
      clinical cleaning procedures, respectively. The Shore A hardness was evaluated in
      a durometer (Teclock GS-709A), with a penetrating load of 10N for 1 second. Any
      macroscopic changes, such as loss of color or alteration in surface texture were
      recorded by one observer. All numeric data were subject to ANOVA with repeated
      measures followed by Tukey's test (alpha= 0.05). RESULTS: All materials were
      significantly different, independently to time and treatment. Initially, Luci Sof
      and Sofreliner immersed in either hypochlorite or peroxide increased the hardness
      mean values significantly. These hardness mean values decreased significantly
      after 720 cycles. Molloplast-B showed no significant difference after the
      treatments, in any time. CONCLUSIONS: Denture cleansers had no effect on hardness
      of the resilient denture liners evaluated after 2 years of in vivo simulated
      conditions of hygiene. Sofreliner was the smoothest material before and after all
      treatments.

PMID- 19089279
TI  - Self-perception of side effects by adolescents in a chlorhexidine-fluoride-based
      preventive oral health program.
AB  - OBJECTIVE: The objective of this study was to evaluate the incidence of adverse
      effects reported by adolescents following 14 days of use of a mouthrinse
      containing 0.05% NaF+0.12% chlorhexidine. METHODS: This double-blind study was
      developed as part of a randomized clinical trial. The adolescents enrolled to the
      study were randomly divided into two groups to use either: 0.05% NaF+0.12%
      chlorhexidine (G1, n=85) or 0.05% NaF (G2, n=85). Both groups used a 10mL
      solution of the mouthwash during 1 minute daily for 2 weeks under supervision.
      After that period, the subject's acceptance of taste was measured using a verbal
      descriptive scale (Labeled Magnitude Scale - LMS). Participants were also
      interviewed regarding the occurrence of possible adverse effects during treatment
      (temporary palate disorders, tooth staining or unpleasant taste). The
      proportional differences between the groups were tested using the chi-square
      test. RESULTS: Palate changes were reported by 26% of participants of each group;
      17.7% of G1 and 32% of G2 reported an unpleasant taste (p = 0.062), while
      staining was reported by 55% of G1 and 68.9% of G2 (p = 0.117). Absenteeism rates
      were similar in both groups (G1= 2.58 +/- 2.69; G2=2.81 +/- 2.39), p=0.362.
      CONCLUSION: Adherence was high in both groups and side effects reported by
      subjects were not perceived by them as being important. Since subjects'
      acceptance and compliance is fundamental to the success of an oral health
      program, chlorhexidine-fluoride could be a useful resource in a program of plaque
      control.

PMID- 19089280
TI  - Effect of cyclic loading on fracture strength of endodontically treated teeth
      restored with conventional and esthetic posts.
AB  - INTRODUCTION: Esthetic post and core systems were recently introduced. There are
      few reports regarding their behavior under cyclic loading. OBJECTIVES: This study
      compared the effect of cyclic loading on survival rate, residual strength and
      mode of fracture of endodontically treated teeth restored with esthetic and
      direct metallic post systems subjected to mechanical cyclic loading. MATERIALS
      AND METHODS: Thirty canines were endodontically treated, decoronated and prepared
      for metal free ceramic crowns, leaving 1.5 mm of dentin for ferrule effect. They
      were distributed in 3 groups and restored as follows: group 1 with zirconia posts
      (Cosmopost) and glass-ceramic cores (IPS Empress Cosmopost); group 2 with fiber
      reinforced composite posts (FibreKor) and group 3 with titanium posts (AZthec
      Anchor). Direct resin composite (Build It FR Resin Composite) was used as core in
      groups 2 and 3. All specimens were restored with all ceramic crowns (IPS Empress
      2). A resin cement/adhesive system (Cement It/Bond It Primer A+B) was used to
      lute the posts to root canals and metal free porcelain crowns to the teeth
      preparation. Specimens were subjected to mechanical load of 250 N for 500,000x at
      a frequency of 1.7 Hz and then to static load until failure in a universal
      testing machine. Data were analyzed using One-way ANOVA and Fischer Exact tests
      alpha=0.05. RESULTS: All groups had 100% survival rate after cyclic loading;
      fracture strength values (SD) in N were: group 1 = 886.5(170.6), group 2 =
      762.2(113.6) and group 3 = 768.9(72.9); there was no difference among groups
      (p=0.08); the percentage of mode of favorable fracture found was: group 1 = 60%,
      group 2 = 90% and group 3 = 50%; there was no correlation between the mode of
      failure and post and core system used (P=0.142). CONCLUSIONS: Esthetic post and
      core systems showed statistically equivalent fracture strength values, mode of
      failure and survival rate compared to conventional direct metallic post and resin
      composite core system after cyclic loading.

PMID- 19089281
TI  - Marginal adaptation and performance of bioactive dental restorative materials in
      deciduous and young permanent teeth.
AB  - OBJECTIVE: The aim of this study was to investigate the adaptation of different
      types of restorations towards deciduous and young permanent teeth. MATERIAL AND
      METHODS: Class V cavities were prepared in deciduous and young permanent teeth
      and filled with different materials (a conventional glass-ionomer, a resin
      modified glass-ionomer, a poly-acid-modified composite resin and a conventional
      composite resin). Specimens were aged in artificial saliva for 1, 6, 12 and 18
      months, then examined by SEM. RESULTS: The composite resin and the polyacid
      modified composite had better marginal adaptation than the glass-ionomers, though
      microcracks developed in the enamel of the tooth. The glass-ionomers showed
      inferior marginal quality and durability, but no microcracking of the enamel. The
      margins of the resin-modified glass-ionomer were slightly superior to the
      conventional glass-ionomer. Conditioning improved the adaptation of the composite
      resin, but the type of tooth made little or no difference to the performance of
      the restorative material. All materials were associated with the formation of
      crystals in the gaps between the filling and the tooth; the quantity and shape of
      these crystals varied with the material. CONCLUSIONS: Resin-based materials are
      generally better at forming sound, durable margins in deciduous and young
      permanent teeth than cements, but are associated with microcracks in the enamel.
      All fluoride-releasing materials give rise to crystalline deposits.

PMID- 19089282
TI  - Effect of cervical relining of acrylic resin copings on the accuracy of stone
      dies obtained using a polyether impression material.
AB  - The purpose of this study was to evaluate the accuracy of the respective dies
      after polyether elastomeric procedure in the presence or absence of cervical
      contact of the acrylic resin shell with the cervical region, establishing a
      comparison to dies obtained with stock trays. This study consisted of three
      groups with 10 specimens each: 1) acrylic copings without cervical contact, (cn);
      2) acrylic copings with cervical contact (cc); 3) perforated stock tray, (st).
      The accuracy of the resulting dies was verified with the aid of a master crown,
      precisely fit to the master steel die. ANOVA test found statistically significant
      differences among groups (p<0.001). Tukey's test found that the smallest
      discrepancy occurred in group cn, followed by cc, while the st group presented
      the highest difference (cc x cn: p=0.007; st x cn: p<0.001; st x cc: p<0.001).

PMID- 19089283
TI  - Biocompatibility of different intracanal medications in rat bucal submucosa
      tissue.
AB  - The aim of this study was to analyze the buccal tissue responses of Wistar rats
      to 2% chlorhexidine solution, calcium hydroxide and the association of both
      products. For this purpose, 30 specimens were randomly implanted in the filtrum
      of the four upper and lower hemiarches with a polyethylene tube containing one of
      the following substances: 2% chlorhexidine solution, calcium hydroxide and 2%
      chlorhexidine solution (test groups); calcium hydroxide and distilled water and
      distilled water (control groups). Ten rats each were distributed according to
      time interval of evaluation at 7, 15 and 30 days. The histological sections were
      stained with Harris hematoxylin and eosin. Analysis was performed with an optical
      microscope at x100, x200 and x400 magnifications by an expert examiner blinded to
      the materials. The sections were classified by scores attributed to inflammatory
      events and by a ranking determined according to the severity of the inflammation.
      The results of the inflammatory events and severity ranking were submitted to the
      Kruskal-Wallis test at a 0.05 level of significance. No statistically significant
      difference occurred among the tested materials; however, all materials showed a
      decreased of severity with respect to longer time intervals.

PMID- 19089284
TI  - Use of Diagnodent for diagnosis of non-cavitated occlusal dentin caries.
AB  - The purpose of this study was to evaluate the use of a laser fluorescence device
      for detection of occlusal caries in permanent teeth. One hundred and ninety-nine
      non-cavitated teeth from 26 patients aged 10 to 13 years were selected. After
      dental prophylaxis, two previously calibrated dentists examined the teeth. Visual
      inspection, radiographic examination and laser measurements were performed under
      standardized conditions. The validation method was cavity preparation with a
      small cone-shaped diamond bur, when the two examiners agreed about the presence
      of dentin caries. It was found that the laser detection method produced high
      values of sensitivity (0.93) and specificity (0.75) and a moderate positive
      predictive value (0.63). The laser device showed the lowest value of likelihood
      ratio (3.68). Kappa coefficient showed good repeatability for all methods.
      Although the laser device had an acceptable performance, this equipment should be
      used as an adjunct method to visual inspection to avoid false positive results.

PMID- 19089285
TI  - Comparative SEM evaluation of three solvents used in endodontic retreatment: an
      ex vivo study.
AB  - This study compared, by scanning electron microscopy (SEM), the efficacy of three
      solvents on the removal of filling materials from dentinal tubules during
      endodontic retreatment. Forty human maxillary canines with straight canals were
      prepared according to a crown-down technique and enlarged to a#30 apical file
      size, before obturation with gutta-percha and a zinc-oxide-eugenol based sealer.
      The samples were stored for 3 months before being randomly assigned to four
      groups: chloroform (n=10), orange oil (n=10), eucalyptol (n=10) and control
      (n=10). Solvents were applied to a reservoir created on the coronal root third
      using Gates Glidden drills. The total time for retreatment using the solvents was
      5 minutes per tooth. Following retreatment the roots were split longitudinally
      for SEM evaluation. SEM images were digitized, analyzed using Image ProPlus 4.5
      software, and the number of dentinal tubules free of filling material from the
      middle and apical thirds was recorded. No significant difference was found among
      the solvent groups regarding the number of dentinal tubules free of root filling
      remnants in the middle and apical root thirds (p>0.05). However, the control
      group had fewer dentinal tubules free of filling material (p<0.05). Under the
      tested conditions, it may be concluded that there was no significant difference
      among the solvents used to obtain dentinal tubules free of filling material
      remnants.

PMID- 19089286
TI  - Comparative analysis of the shrinkage stress of composite resins.
AB  - The aim of this study was to compare the shrinkage stress of composite resins by
      three methods. In the first method, composites were inserted between two
      stainless steel plates. One of the plates was connected to a 20 kgf load cell of
      a universal testing machine (EMIC-DL-500). In the second method, disk-shaped
      cavities were prepared in 2-mm-thick Teflon molds and filled with the different
      composites. Gaps between the composites and molds formed after polymerization
      were evaluated microscopically. In the third method, the wall-to-wall shrinkage
      stress of the resins that were placed in bovine dentin cavities was evaluated.
      The gaps were measured microscopically. Data were analyzed by one-way ANOVA and
      Tukey's test (alpha=0.05). The obtained contraction forces were: Grandio = 12.18
      +/- 0.428N; Filtek Z 250 = 11.80 +/- 0.760N; Filtek Supreme = 11.80 +/- 0.707 N;
      and Admira = 11.89 +/- 0.647 N. The gaps obtained between composites and Teflon
      molds were: Filtek Z 250 = 0.51 +/- 0.0357%; Filtek Supreme = 0.36 +/- 0.0438%;
      Admira = 0.25 +/- 0.0346% and Grandio = 0.16 +/- 0.008%. The gaps obtained in
      wall-to-wall contraction were: Filtek Z 250 = 11.33 +/- 2.160 microm; Filtek
      Supreme = 10.66 +/- 1.211 microm; Admira = 11.16 +/- 2.041 microm and Grandio =
      10.50 +/- 1.224 microm. There were no significant differences among the composite
      resins obtained with the first (shrinkage stress generated during polymerization)
      and third method (wall-to-wall shrinkage). The composite resins obtained with the
      second method (Teflon method) differed significantly regarding gap formation.

PMID- 19089287
TI  - Effect of light-curing units and activation mode on polymerization shrinkage and
      shrinkage stress of composite resins.
AB  - The aim of this study was to evaluate the polymerization shrinkage and shrinkage
      stress of composites polymerized with a LED and a quartz tungsten halogen (QTH)
      light sources. The LED was used in a conventional mode (CM) and the QTH was used
      in both conventional and pulse-delay modes (PD). The composite resins used were
      Z100, A110, SureFil and Bisfil 2B (chemical-cured). Composite deformation upon
      polymerization was measured by the strain gauge method. The shrinkage stress was
      measured by photoelastic analysis. The polymerization shrinkage data were
      analyzed statistically using two-way ANOVA and Tukey test (p < or = 0.05), and
      the stress data were analyzed by one-way ANOVA and Tukey's test (p < or = 0.05).
      Shrinkage and stress means of Bisfil 2B were statistically significant lower than
      those of Z100, A110 and SureFil. In general, the PD mode reduced the contraction
      and the stress values when compared to CM. LED generated the same stress as QTH
      in conventional mode. Regardless of the activation mode, SureFil produced lower
      contraction and stress values than the other light-cured resins. Conversely, Z100
      and A110 produced the greatest contraction and stress values. As expected, the
      chemically cured resin generated lower shrinkage and stress than the light-cured
      resins. In conclusion, The PD mode effectively decreased contraction stress for
      Z100 and A110. Development of stress in light-cured resins depended on the
      shrinkage value.

PMID- 19089288
TI  - Critical analysis of artificial teeth for endodontic teaching.
AB  - The purpose of this study was to evaluate the use of artificial teeth for
      endodontic teaching. A questionnaire was prepared and submitted to 18 professors
      of Endodontics from different Brazilian universities to evaluate the following
      features of five cloudy resin artificial teeth: internal and external anatomy;
      coronal chambers regarding their size, shape and canal path; root canal regarding
      their size, shape and position; fulfillment of the pulp chamber and root canals
      by considering the texture, quantity, color, and ease of handling; resin hardness
      and visualization of the radiographic image. The results presented favorable
      opinions, in terms of internal and external anatomy, coronal pulp chambers and
      root canal and handling and radiographic imaging. The contents of the pulp space
      and hardness of the teeth were considered satisfactory. The average grade
      assigned to the artificial tooth quality was 8.4, in a 0-10 scale. In conclusion,
      the artificial teeth have potential to replace the natural teeth in endodontic
      teaching; however, improvements are still necessary to reach a better quality
      model.

PMID- 19089289
TI  - Sealing ability of grar MTA AngelusTM, CPM TM and MBPc used as apical plugs.
AB  - This study evaluated the sealing ability of apical plugs fabricated with gray MTA
      Angelus sealer, CPM TM sealer and MBPc sealer. The root canals of 98 extracted
      single-rooted human teeth were instrumented with #5 to #1 Gates Glidden drills
      according to the crown-down technique until the #1 drill could pass through the
      apical foramen. The specimens were then prepared with K-files, starting with an
      ISO 50 until an ISO 90 could be visualized 1 mm beyond the apex. After root canal
      preparation, the external surface of each root was rendered impermeable and roots
      were assigned to 3 experimental groups (n = 30), which received a 5-mm thick
      apical plug of gray MTA Angelus, CPM and MBPc, and two control groups (n=4). The
      remaining portion of the canal in the experimental groups was filled by the
      lateral condensation technique. The teeth of each group, properly identified,
      were fixed on utility wax by their crowns and were placed in plastic flasks,
      leaving the apex free and facing upward. The flasks were filled with 0.2%
      Rhodamine B solution, pH 7.0, so as to completely cover the root apex of all
      teeth. The sealing ability was analyzed by measuring 0.2% Rhodamine B leakage
      after all groups had been maintained in this solution for 48 hours. Data were
      analyzed statistically by Kruskal-Wallis test and Dunn test with a=5%. The
      results showed that, among the tested materials used for fabrication of apical
      plugs, MBPc sealer had the least amount of leakage with statistically significant
      difference (p<0.05).

PMID- 19089290
TI  - Preload and torque removal evaluation of three different abutment screws for
      single standing implant restorations.
AB  - Several authors still consider the mechanical problems of fracture and component
      loosening as the main causes of failure of implant-supported restorations. The
      purpose of this in vitro study was to compare the preload of three types of screw
      for transmucosal abutment attachment used in single implant-supported prosthesis
      through strain gauge and removal torque measurements. Three external hex fixtures
      were used, and each received a transmucosal abutment (Cera One), which was fixed
      to the implant with its respective screw: Group A- gold screw, Group B- titanium
      screw and Group C- surface-treated titanium screw (Ti-Tite). Ten screws of each
      type were attached applying a 30.07+/-0.28 Ncm torque force and maintained in
      position for 5 minutes. After this, the preload values were measured using strain
      gauges and a measurement cell. Gold screws presented higher preload values
      (131.72+/-8.98 N), followed by surface-treated titanium screws (97.78+/-4.68 N)
      and titanium screws (37.03+/-5.69 N). ANOVA (p<0.05) and Tukey's test (p<0.05)
      were applied. Statistically significant differences were found among the groups
      for both preload and removal torque values. In conclusion, gold screws may be
      indicated to achieve superior longevity of the abutment-implant connection and,
      consequently, prosthetic restoration due to greater preload values yielded.

PMID- 19089291
TI  - Response of the periapical tissue of dogs' teeth to the action of citric acid and
      EDTA.
AB  - The purpose of this study was to analyze the inflammatory response of dog's
      periapical tissues to 17% trisodium EDTA salt (pH 8.0) and 1% citric acid (pH
      2.0). Saline was used as a control. Six adult dogs were used as the biological
      model of the study. The experimental units comprised 56 roots of mandibular
      molars (first and second) and premolars (first, second and third). After coronal
      opening, pulpectomy and root canal instrumentation were performed using the above
      mentioned irrigating solutions. After 24 and 48 hours, the animals were
      euthanized and the teeth and their supporting tissues were removed and
      histologically processed. The sections were stained with hematoxylin and eosin
      and analyzed histopathologically with a light microscope at x100 magnification.
      The histological analysis focused on the occurrence of acute inflammatory
      response. The presence of swelling, vasodilatation and inflammatory cells were
      evaluated and the degree of inflammation was determined for each case. Data were
      analyzed by Fisher's exact test using the SPSS software with a confidence
      interval of 95% (p<0.05). 17% EDTA and 1% citric acid caused inflammatory
      responses in dog's periapical tissues with no significant differences to each
      other or to saline (control) at either the 24-hour (p=0.482) or 48-hour (p=0.377)
      periods. It may be concluded that the inflammatory response was of mild intensity
      for the tested substances.

PMID- 19089293
TI  - Root caries in areas with and without fluoridated water at the Southeast region
      of Sao Paulo State, Brazil.
AB  - This study aimed to investigate root caries prevalence in areas with and without
      water fluoridation at the Southeast region of Sao Paulo State, in the adult
      population, employees of public and private schools, and elderly population.
      Epidemiological surveys were conducted according to the World Health Organization
      guidelines (1997), including 1,475 dentate individuals aged 35 to 44 years and 65
      to 74 years, living in cities representing the southeast of Sao Paulo State, with
      (n=872) or without (n=603) fluoridated water supply. Statistical analysis was
      performed by Mann-Whitney and Chi-square tests at a significance level of 5%. The
      prevalence of root caries was 15.6% for the 35-44-year-old age group and 31.8%
      for the 65-74-year-old age group . There were no statistically significant
      differences (p>0.05) in the occurrence of root caries according to water
      fluoridation, although individuals living at non-fluoridated areas presented
      higher percentage of missing teeth; also, there was higher mean number of intact
      roots at fluoridated areas (p<0.05). Most individuals with gingival recession,
      both adults and elderly, did not have root caries experience. In this study, root
      caries prevalence was lower in areas with fluoridated water. Due to the reduced
      prevalence of edentulism and increased number of people keeping their natural
      teeth for a longer period, a future increase in root caries is expected,
      highlighting the importance of studies related to water fluoridation and its
      relationship with the oral health of adults and elderly, especially referring to
      tooth root.

PMID- 19089292
TI  - Correlation between margin fit and microleakage in complete crowns cemented with
      three luting agents.
AB  - Microleakage can be related to margin misfit. Also, traditional microleakage
      techniques are time-consuming. This study evaluated the existence of correlation
      between in vitro margin fit and a new microleakage technique for complete crowns
      cemented with 3 different luting agents. Thirty human premolars were prepared for
      full-coverage crowns with a convergence angle of 6 degrees, chamfer margin of 1.2
      mm circumferentially, and occlusal reduction of 1.5 mm. Ni-Cr cast crowns were
      cemented with either zinc phosphate (ZP) (S.S. White), resin-modified glass
      ionomer (RMGI) (Rely X Luting Cement) or a resin-based luting agent (RC)
      (Enforce). Margin fit (seating discrepancy and margin gap) was evaluated
      according to criteria in the literature under microscope with 0.001 mm accuracy.
      After thermal cycling, crowns were longitudinally sectioned and microleakage
      scores at tooth-cement interface were obtained and recorded at x100
      magnification. Margin fit parameters were compared with the one-way ANOVA test
      and microleakage scores with Kruskal-Wallis and Dunn's tests (alpha=0.05).
      Correlation between margin fit and microleakage was analyzed with the Spearman's
      test (alpha=0.05). Seating discrepancy and marginal gap values ranged from 81.82
      microm to 137.22 microm (p=0.117), and from 75.42 microm to 78.49 microm
      (p=0.940), respectively. Marginal microleakage scores were ZP=3.02, RMGI=0.35 and
      RC=0.12 (p<0.001), with no differences between RMGI and RC scores. The
      correlation coefficient values ranged from -0.27 to 0.30 (p>0.05). CONCLUSION:
      Margin fit parameters and microleakage showed no strong correlations; cast crowns
      cemented with RMGI and RC had lower microleakage scores than ZP cement.

PMID- 19089294
TI  - Analysis of the ethical aspects of professional confidentiality in dental
      practice.
AB  - From the point of view of deontological ethics, privacy is a moral right that
      patients are entitled to and it is bound to professional confidentiality.
      Otherwise, the information given by patients to health professionals would not be
      reliable and a trustable relationship could not be established. The aim of the
      present study was to assess, by means of questionnaires with open and closed
      questions, the awareness and attitudes of 100 dentists working in the city of
      Andradina, Sao Paulo State, Brazil, with respect to professional confidentiality
      in dental practice. Most dentists (91.43%) reported to have instructed their
      assistants on professional confidentiality. However, 44.29% of the interviewees
      showed to act contradictorily as reported talking about the clinical cases of
      their patients to their friends or spouses. The great majority of professionals
      (98.57%) believed that it is important to have classes on Ethics and Bioethics
      during graduation and, when asked about their knowledge of the penalties imposed
      for breach of professional confidentiality, only 48.57% of them declared to be
      aware of it. Only 28.57% of the interviewees affirmed to have exclusive access to
      the files; 67.14% reported that that files were also accessed by their secretary;
      1.43% answered that their spouses also had access, and 2.86% did not answer. From
      the results of the present survey, it could be observed that, although dentists
      affirmed to be aware of professional confidentiality, their attitudes did not
      adhere to ethical and legal requirements. This stand of health professionals has
      contributed to violate professional ethics and the law itself, bringing problems
      both to the professional and to the patient.

PMID- 19089295
TI  - Clinical management for epidermolysis bullosa dystrophica.
AB  - Epidermolysis bullosa (EB) consists of a group of genetic hereditary disorders in
      which patients frequently present fragile skin and mucosa that form blisters
      following minor trauma. More than 20 subtypes of EB have been recognized in the
      literature. Specific genetic mutations are well characterized for most the
      different EB subtypes and variants. The most common oral manifestations of EB are
      painful blisters affecting all the oral surfaces. Dental treatment for patients
      with EB consists of palliative therapy for its oral manifestations along with
      typical restorative and periodontal procedures. The aim of this article is to
      describe two dental clinical treatments of recessive dystrophic EB cases and
      their specific clinical manifestations. The psychological intervention required
      during the dental treatment of these patients is also presented.

PMID- 19089296
TI  - Comparative proteomics analysis of cytokeratin and involucrin expression in
      lesions from patients with systemic lupus erythematosus.
AB  - To get a better understanding of the abnormal differentiation or maturation of
      keratinocytes, we studied the expression and distribution of cytokeratin and
      involucrin in lesions from systemic lupus erythematosus patients. Two groups of
      10 specimens each from systemic lupus erythematosus and normal controls were
      analyzed by two-dimensional gel electrophoresis, mass spectrometric protein
      identification, Western blotting and immunohistochemistry. Our results showed
      that keratin 1 (K1)/K10 together with the new synthesis of K6/K16 were down
      regulated and that K5/K14, K2e and involucrin were up-regulated. We found that
      involucrin was strongly stained in lower epidermal cell layers while K1/10 was
      weakly stained, particularly when compared with staining in normal epidermis.
      Additionally, we found that the expression of involucrin was increased. These
      results imply an aberrant early and terminal differentiation stage in the
      epidermis of systemic lupus erythematosus, which may be associated with
      inflammatory cytokines released during the wound healing response of lesion.

PMID- 19089297
TI  - Enhancement of cytotoxic T lymphocyte activity by dendritic cells loaded with Tat
      protein transduction domain-fused hepatitis B virus core antigen.
AB  - The protein transduction domain (PTD) of human immunodeficiency virus-1-Tat
      protein has a unique potency to penetrate the cellular membranes. To synthesize
      the sequence of Tat-PTD47-57 and hepatitis B virus core antigen (HBcAg), we
      spliced these sequences and linked a fusion gene into the pMAL-c2x vector. The
      fusion proteins were purified by affinity chromatography and pulsed with bone
      marrow-derived dendritic cells (DCs), and the transduction of recombinant protein
      was detected by immunofluorescence antibody assay. Results showed that
      recombinant PTD-HBcAg could penetrate into DC cytoplasm while recombinant HBcAg
      was detected on the surface of cells. The percentage of DC surface molecules,
      such as CD80, CD86 and major histocompatibility complex II, and production of
      cytokine (IL-12p70) induced by recombinant PTD-HBcAg were significantly higher
      than those induced by recombinant HBcAg or tumor necrosis factor-alpha. DCs
      treated with PTD-HBcAg induced T cells to differentiate into specific cytotoxic T
      lymphocytes (CTLs) and enhanced the CTL killing response. In conclusion, the
      expressed and purified PTD-HBcAg fusion protein could penetrate into cells
      through the plasma membrane, promote DC maturation, and enhance T cells response
      to generate HBcAg-specific CTLs efficiently.

PMID- 19089298
TI  - Expression analysis of a novel pyridoxal kinase messenger RNA splice variant,
      PKL, in oil rape suffering abiotic stress and phytohormones.
AB  - Pyridoxal kinase is key enzyme for the biosynthesis of pyridoxal 5'-phosphate,
      the biologically active form of vitamin B6, in the salvage pathway. A pyridoxal
      kinase gene, BnPKL (GenBank accession No. DQ463962), was isolated from oilseed
      rape (Brassica napus L.) following water stress through rapid amplification of
      complementary DNA (cDNA) ends. The results showed that the gene had two splice
      variants: PKL and PKL2. PKL, the long cDNA, encodes a 334 amino acid protein with
      a complete ATP-binding site, pyridoxal kinase-binding site and dimer interface
      site of a pyridoxal kinase, while PKL2, the short cDNA, lacked a partial domain.
      Southern blot showed that there were two copies in Brassica napus. The expression
      of BnPKL cDNA could rescue the mutant phenotype of Escherichia coli defective in
      pyridoxal kinase. Real-time reverse transcription-polymerase chain reaction
      revealed that the relative abundance of two transcripts are modulated by
      development and environmental stresses. Abscisic acid and NaCl were inclined to
      decrease PKL expression, but H2O2 and cold temperatures induced the PKL
      expression. In addition, the PKL expression could be transiently induced by
      jasmonate acid at an early stage, abscisic acid, salicylic acid and jasmonate
      acid enhanced the PKL expression in roots. Our results demonstrated that BnPKL
      was a pyridoxal kinase involved in responses to biotic and abiotic stresses.

PMID- 19089299
TI  - Intein-mediated rapid purification of recombinant maxadilan and M65 and their
      acute effects on plasma glucose.
AB  - Maxadilan is a potent vasodilatory peptide present in the salivary glands of the
      sand fly. Maxadilan and M65, a deletion variation of maxadilan, are agonist- and
      antagonist-specific for the PAC1 receptor. In order to obtain the recombinant
      maxadilan and M65 efficiently by intein-mediated single column purification, the
      genes encoding maxadilan and M65 were designed, synthesized and cloned into
      Escherichia coli expression vector pKYB. The recombinant maxadilan and M65 with
      homogeneity over 95% were released from the chitin-bound intein tag by beta
      mercaptoethanol. Intraperitoneal injection of the recombinant maxadilan caused an
      acute elevation of plasma glucose, imitating pituitary adenylate cyclase
      activating polypeptide (PACAP) 27, in NIH mice, while the VPAC1-agonist and VPAC2
      agonist had no significant effects on the levels of plasma glucose. M65 alone had
      no effect on the plasma glucose, but blocked the glucose excursion caused by
      maxadilan by 12.7% and blocked the glucose excursion caused by the PACAP 27 by
      11.6%. The acute effects of the recombinant maxadilan and M65 on the plasma
      glucose indicated that they had the characteristics as the agonist and antagonist
      for PAC1.

PMID- 19089300
TI  - Inhibition of Lux quorum-sensing system by synthetic N-acyl-L-homoserine lactone
      analogous.
AB  - In the present study, we investigated the inhibition of the Lux quorum-sensing
      system by N-acyl cyclopentylamine (Cn-CPA). The Lux quorum-sensing system
      regulates luminescence gene expression in Vibrio fischeri. We have already
      reported on the synthesis of Cn-CPA and their abilities as inhibitors of the
      quorum-sensing systems in Pseudomonas aeruginosa and Serratia marcescens. In the
      case of Pseudomonas aeruginosa (Las and Rhl quorum-sensing system) and Serratia
      marcescens (Spn quorum-sensing system), specific Cn-CPA with a particular acyl
      chain length showed the strongest inhibitory effect. In the case of the Lux
      quorum-sensing system, it was found that several kinds of Cn-CPA with a range
      from C5 to C10 showed similar strong inhibitory effects. Moreover, the inhibitory
      effect of Cn-CPA on the Lux quorum-sensing system was stronger than that of
      halogenated furanone, a natural quorum-sensing inhibitor.

PMID- 19089301
TI  - Purification of melibiose-binding lectins from two cultivars of Chinese black
      soybeans.
AB  - A dimeric 50 kDa melibiose-binding lectin was isolated from the seeds of the
      cultivar of soybean (Glycine max), called the small glossy black soybean. The
      isolation procedure comprised ion exchange chromatography on Q Sepharose, SP
      Sepharose and Mono Q followed by gel filtration on Superdex 75. The lectin was
      adsorbed on all three ion exchangers, and it exhibited an N-terminal sequence
      identical to that of soybean lectin. Of all the sugars tested, melibiose most
      potently inhibited the hemagglutinating activity of the lectin, which was stable
      between pH 3-12 and 0-70 degrees C. The lectin evoked maximal mitogenic response
      at about the same molar concentration as Con A. However, the response was much
      weaker. The soybean lectin inhibited the activity of HIV-1 reverse transcriptase
      as well as the proliferation of breast cancer MCF7 cells and hepatoma HepG2 cells
      with an IC50 of 2.82 microM, 2.6 microM and 4.1 microM, respectively. There was
      no antifungal activity. Another lectin was isolated from a different cultivar of
      soybean called little black soybean. The lectin was essentially similar to small
      glossy black soybean lectin except for a larger subunit molecular mass (31 kDa),
      a more potent mitogenic activity and lower thermostability. The results indicate
      that different cultivars of soybean produce lectins that are not identical in
      every aspect.

PMID- 19089302
TI  - Casein kinase II interacts with prion protein in vitro and forms complex with
      native prion protein in vivo.
AB  - The most essential and crucial step during the pathogenesis of transmissible
      spongiform encephalopathy is the conformational change of cellular prion protein
      to pathologic isoform. Casein kinase II (CK2) is a ubiquitously expressed and
      evolutionarily conserved pleiotropic protein kinase that is essential for
      viability. To explore the possible molecular interaction between CK2 and prion
      protein (PrP), the full-length sequences of human CK2alpha and CK2beta
      complementary DNA were amplified with reverse transcription-polymerase chain
      reaction using the total messenger RNA from cell line SH-SY5Y as the template;
      then, the fusion proteins histidine-CK2alpha and glutathione S-transferase
      histidine-CK2beta were expressed in Escherichia coli. The interaction between CK2
      and PrP was evaluated with co-immunoprecipitation and pull-down assays. The
      results demonstrated that recombinant PrP bound specifically with CK2alpha, but
      not with CK2beta. The native CK2 and PrP in hamster brains interacted with each
      other, forming protein complexes. Three different glycosylated forms of PrP
      (diglycosylated, monoglycosylated and unglycosylated PrP) from normal brains
      interacted with the CK2alpha subunit, though the unglycosylated PrP seemed to
      have a stronger binding ability with CK2alpha subunit. The domain responsible for
      interacting with CK2alpha was located at the C-terminal segment of PrP (residues
      91-231). This study proposed reliable experimental data for the molecular
      interaction between PrP and CK2alpha (both in recombinant and native categories),
      scientific clues for further assessing the potential biological significance of
      the PrP-CK2 interaction, and the possible role of CK2 in the pathogenesis of
      prion diseases.

PMID- 19089303
TI  - DNA microarray analysis of fluconazole resistance in a laboratory Candida
      albicans strain.
AB  - Several mechanisms are responsible for the acquired fluconazole (FLC) resistance
      in Candida albicans. In this study, we developed a FLC-resistant C. albicans
      strain through serial cultures of a FLC-susceptible C. albicans strain with
      inhibitory concentrations of FLC. Complimentary DNA microarray analysis and real
      time reverse transcription-polymerase chain reaction were used to investigate
      gene expression changes during the acquisition of azole resistance in the
      susceptible parental strain and the resistant daughter strain. The differentially
      expressed genes represented functions as diverse as transporters (e.g. CDR1,
      PDR17), ergosterol biosynthesis (e.g. ERG2, ERG9), sterol metabolism (e.g. ARE2,
      IPF6464), energy metabolism (e.g. ADH3, AOX2) and transcription factors (e.g.
      FCR1, ECM22). Functional analysis revealed that energy-dependent efflux activity
      of membrane transporters increased and that ergosterol content decreased with the
      accumulation of sterol intermediates in the resistant strain as compared with the
      susceptible strain. We found that a point mutation (N977K) in transcription
      factor TAC1 that resulted in hyperactivity of Tac1 could be the reason for
      overexpression of CDR1, CDR2, and PDR17 in the resistant strain. Furthermore, a
      single amino acid difference (D19E) in ERG3 that led to the inactivation of Erg3
      could account for both sterol precursor accumulation and the changes in the
      expression of ergosterol biosynthesis genes in this resistant strain. These
      findings expand the understanding of potential novel molecular targets of FLC
      resistance in clinical C. albicans isolates.

PMID- 19089304
TI  - Identification and characterization of the minimal androgen-regulated kidney
      specific kidney androgen-regulated protein gene promoter.
AB  - The kidney androgen-regulated protein (Kap) gene is tissue specific and regulated
      by androgen in mouse kidney proximal tubule cells (PTCs). In the present study,
      we aimed to identify the minimal PTC-specific androgen-regulated Kap promoter and
      analyze its androgen response elements (AREs). A deletion series of the Kap1542
      promoter/luciferase constructs were assayed in opossum kidney (OK) PTCs in the
      presence or absence of 15 nM dihydrotestosterone (DHT). Kap1542 and Kap637 had
      low activity and no androgen induction; Kap224 had a basal activity that was 4-
      to 5-fold higher than that of Kap1542, but was only slightly induced by DHT.
      Kap147 had a basal activity that was 2- to 3-fold higher than that of Kap1542 and
      was induced by DHT 4- to 6-fold. Kap77 abolished basal promoter activity but was
      still induced by DHT. Results showed that, in vitro, Kap147 was a minimal
      androgen-regulated promoter. Transient transfection in different cells
      demonstrated that Kap147 specifically initiated reporter gene expression in PTCs.
      Sequence analysis revealed two potential AREs located at positions -124 and -39
      of Kap147. Mutational assays showed that only the ARE at -124 was involved in
      androgen response in OK cells. Electrophoretic mobility shift assay also verified
      -124 ARE bound specifically to androgen receptor. In conclusion, we defined the
      minimal Kap147 promoter that may be a good model for the study of kidney PTC
      specific expression and molecular mechanisms that lead to an androgen-specific
      responsiveness in vivo.

PMID- 19089305
TI  - Transvaginal pelvic organ prolapse repair of anterior enterocele following
      cystectomy in females.
AB  - This study aims to highlight pelvic organ prolapse (POP) in females following
      radical cystectomy and to describe our experiences with their management. This is
      a retrospective case series of five women who had symptomatic POP following
      radical cystectomy and ileal conduit urinary diversion. All patients presented
      with a midline anterior enterocele with atrophic ulcerated vaginal skin. One
      patient presented with small bowel evisceration and required an emergency
      surgical repair. The average time for presentation was 10.6 +/- 6.5 months after
      cystectomy. In all cases, repair was done via a transvaginal approach. Three
      patients underwent fascial repair, one colpocleisis, and one bilateral
      iliococcygeal repair. In three cases, we had to use mesh for reinforcement. Two
      patients underwent ancillary procedures because of POP recurrence. Surgical
      repair of POP in women following radical cystectomy is challenging especially if
      vaginal length is to be maintained. Transvaginal repair is feasible and using
      synthetic mesh may be necessary.

PMID- 19089306
TI  - Female sexual function following surgery for stress urinary incontinence: tension
      free vaginal versus transobturator tape procedure.
AB  - The aim of this study was to compare sexual function outcome following tension
      free vaginal (TVT) versus transobturator tape (TOT) for stress urinary
      incontinence (SUI). All women who underwent TVT or TOT procedures for SUI with no
      concomitant prolapse repair between January 2002 and July 2007 were sent a
      retrospective pre-post questionnaire. Eighty-one and 64 women were sexually
      active before and after TVT and TOT procedures, respectively. Sexual function
      outcome did not differ pre- and postoperatively for the TVT and TOT groups, and
      postoperatively between the two groups. Responders reported an improvement of
      intercourse satisfaction in 23 (29.5%) and 21 (32.9%) cases, whereas 14 (17.3%)
      and eight (12.5%) complained of sexual function deterioration after TVT and TOT
      procedure, respectively (p = 0.43). This study suggests that anti-incontinence
      surgery can have a positive and negative outcome on sexual function, with no
      significant differences between the TVT and TOT procedures.

PMID- 19089307
TI  - Short homologous sequences are strongly associated with the generation of
      chimeric RNAs in eukaryotes.
AB  - Chimeric RNAs have been reported in varieties of organisms and are conventionally
      thought to be produced by trans-splicing of two or more distinct transcripts.
      Here, we conducted a large-scale search for chimeric RNAs in the budding yeast,
      fruit fly, mouse, and human. Thousands of chimeric transcripts were identified in
      these organisms except in yeast, in which five chimeric RNAs were observed. RT
      PCR experiments for a sample of yeast and fly chimeric transcripts using specific
      primers show that about one-third of these chimeric RNAs can be reproduced. The
      results suggest that at least a considerable amount of chimeric RNAs is unlikely
      from aberrant transcription or splicing, and thus formation of chimeric RNAs is
      probably a widespread process and can greatly contribute to the complexity of the
      transcriptome and proteome of organisms. However, only a small fraction (<20%) of
      these chimeric RNAs has GU-AG at the junction sequences which fits the classical
      trans-splicing model. In contrast, we observed that about half of the chimeric
      RNAs have short homologous sequences (SHSs) at the junction sites of the source
      sequences. Our sequence mutation experiments in yeast showed that disruption of
      SHSs resulted in the disappearance of the corresponding chimeric RNAs, suggesting
      that SHSs are essential for generating this kind of chimeric RNA. In addition to
      the classical trans-splicing model, we propose a new model, the transcriptional
      slippage model, to explain the generation of those chimeric RNAs synthesized from
      templates with SHSs.

PMID- 19089308
TI  - Truncus arteriosus with an unusual ventricular septal defect.

PMID- 19089309
TI  - Pediatric giant cell myocarditis and orbital myositis.
AB  - Giant cell myocarditis is a rare but often fatal form of myocarditis that often
      requires cardiac transplantation and has been associated with autoimmune
      diseases. We describe a 14-year-old female who developed painful proptosis and
      was diagnosed clinically and histologically with orbital myositis that improved
      with corticosteroid therapy. Approximately 2 months later, she developed
      abdominal pain, vomiting, weight gain, and fatigue. She was diagnosed with
      congestive heart failure and cardiomyopathy, and endomyocardial biopsy revealed
      giant cell myocarditis. She was treated with immunosuppressive agents and has
      responded well, without the need for cardiac transplantation. Three previous case
      reports have described an association between giant cell myocarditis and orbital
      myositis, but we present the first pediatric case report. We conclude that if
      orbital myositis is diagnosed in a patient, regardless of age, cardiac function
      should be closely monitored to detect myocarditis, which may affect the overall
      outcome.

PMID- 19089310
TI  - Postnatal changes in the styloid process, vagina processus styloidei, and
      stylomastoid foramen in relation to the function of muscles originating from the
      styloid process.
AB  - We investigated age-related changes in the styloid process in 88 skulls, aged
      from 5 months to 85 years of age. The osseous styloid process was not well
      developed in children. Its length increased significantly with age (from 2.3 mm
      in 11-20 age group to 16.3 mm in 61-85 group). In adolescent specimens (11-20
      years of age), the median distance from the styloid process to the stylomastoid
      foramen was 0.7-0.8 mm, whereas in adult and old age specimens the two structures
      were completely adjacent or very close, usually less than 0.2 mm. The process was
      missing in 5% of the adult specimens. There was a statistically significant
      positive association between the length of the styloid process with age (r =
      0.3210, 95% CI 0.0817-0.5254; P = 0.0097), whereas the distance from the styloid
      process to the stylomastoid foramen significantly decreased with age (r = 
      0.4518, 95% CI -0.6167 to -0.2490; P = 0.0001). Changes in the length and shape
      of the styloid process reflected altered function of the three muscles
      originating from the styloid process-m. stylopharyngeus, m. stylohyoideus and m.
      styloglossus. They have a common function of lifting the aerodigestive elements
      upward and backward, after the descent of the aerodigestive tract and final
      morphological differentiation of the vocal system during puberty. Relationship
      between altered muscle function and the morphology of the styloid process are
      important for understanding the clinical syndromes related to the styloid
      process, such as Eagle's syndrome.

PMID- 19089312
TI  - Resection of the intrapancreatic bile duct preserving the pancreas.
AB  - Benign neoplasms of the distal bile duct are rare, but pose a therapeutic
      challenge. Usually, these lesions are resected by means of ampullectomy if
      located in close proximity to the ampulla of Vateri or by partial
      pancreaticoduodenectomy if located intrapancreatic and distant from the ampulla.
      Here, we present a case of an intrapancreatic benign neuroendocrine tumor that
      was resected by performing a pancreas-preserving distal bile duct resection.
      First, a duodenotomy was carried out and a probe was inserted into the pancreatic
      duct to avoid inadvertent injury. Subsequently, the bile duct was divided
      proximal the lesion and dissected towards the ampulla. Pancreatic parenchyma was
      dissected dorsally and closed using absorbable interrupted sutures. The duodenal
      incision was closed, and reconstruction was performed by an end-to-side
      hepaticojejunostomy and a Roux-Y jejunojejunostomy. The postoperative course of
      the patient was uneventful. In conclusion, pancreas-preserving distal bile duct
      resection might be an option for intrapancreatic benign lesions of the distal
      bile duct that would otherwise require a partial pancreaticoduodenectomy.

PMID- 19089311
TI  - Cholecystocolonic fistula: facts and myths. A review of the 231 published cases.
AB  - BACKGROUND: Cholecystocolonic fistula (CCF) is the second most common
      cholecystoenteric fistula and is often discovered intraoperatively, resulting in
      a challenging situation for the surgeon, who is forced to switch to a complex
      procedure, often in old, unfit patients. Management of this uncommon but possible
      finding is still ill defined. METHODS: An extensive review of 160 articles
      published from 1950 to 2006 concerning 231 cases of CCF was performed. RESULTS:
      CCF is mostly an affliction of women in their sixth to seventh decades and is
      rarely diagnosed preoperatively. Chronic diarrhea is the key symptom in
      nonemergency patients, but, in one-fourth of cases, CCF presents with an acute
      onset, mostly biliary ileus. In one-fourth of patients, a second hepatobiliary
      abnormality is present, including gallbladder cancer in 2% of cases. In
      uncomplicated cases, diverting colostomy is not performed anymore, and
      laparoscopy treatment has been described in specialized centers. Symptomatic
      treatment of concomitant biliary ileus (without treating CCF) is a feasible
      option. Resolution of colonic biliary ileus by interventional endoscopy is
      reported. CONCLUSION: CCF should be considered in differential diagnosis of
      diarrhea, especially in old, female patients. A possible second hepatobiliary
      abnormality should be always investigated. Extemporaneous frozen section should
      be performed if gallbladder cancer is suspected. Depending on clinical
      presentation, different treatments for CCF are indicated, ranging from minimally
      invasive procedures to extensive resection.

PMID- 19089313
TI  - Cholecystectomy by a combined transgastric and transparietal approach using two
      flexible endoscopes.
AB  - OBJECTIVE: This experimental study was designed to assess the technical
      feasibility and benefits of our novel approach for transgastric NOTES (natural
      orifice translumenal endoscopic surgery) cholecystectomy. METHODS: Four pigs were
      subjected to NOTES cholecystectomy by the combined transgastric and transparietal
      approach using two flexible endoscopes. Under the guidance of a transparietal
      endoscope inserted through a trocar placed in the right upper abdomen, a
      gastrotomy was constructed, and a peroral endoscope was advanced into the
      peritoneal cavity through the gastrotomy and moved on retroflexion toward the
      gallbladder. Gallbladder excision with ligation of the cystic artery and duct
      using endoclips was performed using the peroral endoscope. After gastrotomy
      closure with endoclips inside the stomach, intraperitoneal lavage were carried
      out using the transparietal endoscope. RESULTS: A complete gallbladder excision
      was carried out without major adverse events in all cases. The gastrotomies were
      successfully closed using endoclips (n = 3) or by the omentum-plug method (n =
      1). CONCLUSION: This approach is technically feasible and makes transgastric
      NOTES cholecystectomy easier and safer.

PMID- 19089314
TI  - Dopamine transporter immunoreactivity in peripheral blood lymphocytes in multiple
      system atrophy.
AB  - Previous studies showed the reduction of dopamine transporter immunoreactivity
      (DAT-IR) in peripheral blood lymphocytes (PBL) in Parkinson's disease. Here we
      report the reduction of DAT-IR in PBL in the extrapyramidal variant of multiple
      system atrophy. These results suggest the reduction of DAT-IR in PBL in a variety
      of neurodegenerative disorders, provided the presence of damage of the central
      dopaminergic systems. The reduction of DAT-IR in PBL in these disorders may
      represent a compensatory phenomenon aimed at reducing intracellular dopamine
      influx and, consequently, dopamine-mediated aggravation of oxidative stress in
      these cells.

PMID- 19089315
TI  - Metabolism of galactose in the brain and liver of rats and its conversion into
      glutamate and other amino acids.
AB  - Time- and dose-dependent measurements of metabolites of galactose (with glucose
      as control) in various organs of rats are discussed. Not only the liver but
      especially the brain and to a lesser extent the muscles also have the capacity to
      take up and metabolize galactose. Primarily, the concentrations of UDP-galactose,
      a pivotal compound in the metabolism of galactose, and UDP-glucose are measured.
      An important feature lies in the demonstration that galactose and glucose are
      metabolized to amino acids and that the only increases observed in the brain
      appear in the concentrations of glutamate, glutamine, GABA measured after acute
      galactose loads. In addition the increase in the amino acid concentrations after
      galactose has been administered persists for longer periods of time than after
      glucose administration. This conversion of hexoses, especially galactose, to
      amino acids requires the consumption of ammonia equivalents in the brain; this
      finding might stimulate the use of galactose as a new means of removal of this
      neurotoxic compound from the brain in patients suffering from hepatic
      encephalopathy or Alzheimer's disease.

PMID- 19089316
TI  - Time course analysis of gene expression over 24 hours in Fe-deficient barley
      roots.
AB  - Typical for a graminaceous plant, barley secretes mugineic acid-family
      phytosiderophores (MAs) to acquire iron (Fe). Under Fe-deficient conditions, MAs
      secretion from barley roots increases markedly. Secretion shows a diurnal
      pattern, with a clear peak 2-3 h after sunrise and cessation within a few hours.
      Microarray analyses were performed to profile the Fe deficiency-inducible genes
      in barley roots and diurnal changes in the expression of these genes. Genes
      encoding enzymes involved in MAs biosynthesis, the methionine cycle, and
      methionine biosynthesis were highly induced by Fe deficiency. The expression of
      sulfate transporters was also upregulated by Fe deficiency. Therefore, all of the
      genes participating in the MAs pathway from sulfur uptake and assimilation to the
      biosynthesis of MAs were upregulated in Fe-deficient barley roots. In contrast to
      MAs secretion, the transcript levels of these genes did not show diurnal changes.
      The amount of endogenous MAs gradually increased during the day after MAs
      secretion ceased, and was highest before secretion began. These results show that
      MAs biosynthesis, including the supply of the substrate methionine, occurs
      throughout the day, and biosynthesized MAs likely accumulate in barley roots
      until their secretion into the rhizosphere. In contrast, the levels of
      transcripts encoding an Fe(III)-MAs complex transporter, two putative metal-MAs
      complex transporters, and HvYS1 were also increased in Fe-deficient barley roots,
      and the levels of two of these transcripts showed diurnal rhythms. The Fe(III)
      MAs complex transporters may absorb Fe(III)-MAs diurnally, synchronous with the
      diurnal secretion of MAs.

PMID- 19089317
TI  - Rice phot1a mutation reduces plant growth by affecting photosynthetic responses
      to light during early seedling growth.
AB  - The aim of this work was to characterize the phot1 mutant of rice during early
      seedling growth in various light conditions. We isolated the rice T-DNA insertion
      mutant phot1a-1 and compared it to the Tos17 insertion mutant phot1a-2. When
      phot1a mutants were grown under WL (100) and BL (40 miccromol m(-2) s(-1)), they
      demonstrated a considerable reduction in photosynthetic capacity, which included
      decreased leaf CO(2) uptake and plant growth. Pigment analysis showed no
      significant difference between wild-type and mutants in the Chl a:b ratios,
      whereas in the latter, total concentration was reduced (a 2-fold decrease).
      Carotenoid contents of the mutants were also decreased considerably, implying the
      involvement of phot1a in pigment degradation. Deletion of phot1a showed higher
      contents of H(2)O(2) in leaves. Chloroplastic APX and SOD activities were lower
      in the mutants whereas the activities of cytosolic enzymes were increased.
      Immunoblotting indicated reduced accumulation of photosystem proteins (D1, D2,
      CP43, Lhca2, and PsaC) relative to the other light-harvesting complexes in the
      mutant. We conclude that the defect of Os Phot1a affects degradation of
      chlorophylls and carotenoids, and under photosynthetically active photon fluxes,
      mutation of phot1a results in loss of photosynthetic capacity owing to the damage
      of photosystems caused by elevated H(2)O(2) accumulation, leading to a reduction
      in plant growth.

PMID- 19089318
TI  - Proteome alteration of U251 human astrocytoma cell after inhibiting retinoic acid
      synthesis.
AB  - Retinoic acid (Ra) is crucial for the patterning and neuronal differentiation in
      the central nervous system (CNS). Ra deficiency in animals disrupts the motor
      activities and memory abilities. The molecular mechanisms underlying these
      behavior abnormalities remain largely unknown. In the current study, we treated
      the astrocytoma cells with citral, an inhibitor of Ra synthesis. We analyzed the
      differences in the protein concentrations between the treated and untreated
      astrocytoma cells by two-dimensional gel electrophoresis (2-DE), Imagemaster
      software, and matrix-assisted laser desorption/ionization time-of-flight mass
      spectrometry (MALDI-TOF MS). In total, 39 of 46 altered protein spots with
      significant mascot scores were identified representing 36 proteins, that were
      involved in significantly altered glutamate metabolism, lipid metabolism,
      mitochondrial function, and oxidative stress response by Ingenuity Pathway
      Analysis (IPA). Altered 3-phosphoglycerate dehydrogenase (PHGDH) was also
      observed in western blot. These data provide some clues for explaining the
      behavioral changes caused by Ra deficiency, and support the hypothesis that Ra
      signaling is associated with some symptoms of neurodegenerative disorders and
      schizophrenia.

PMID- 19089319
TI  - Serial follow-up study on renal handling of calcium and phosphorus after soil
      replacement in Cd-polluted rice paddies estimated using a general linear mixed
      model.
AB  - A 10-year follow-up study was conducted to investigate the effects of renal
      handling of calcium (Ca) and phosphorus (P) after the removal of cadmium-polluted
      soil in rice paddies and replacing it with nonpolluted soil. Using a general
      linear mixed model, serial changes of Ca and P concentrations in urine and serum
      (Ca-U/S, P-U/S), fractional excretion of Ca (FECa), and percent tubular
      reabsorption of P (%TRP) were determined in 37 persons requiring observation in
      the Cd-polluted Kakehashi River Basin, Japan. Ca-U and Ca-S remained within the
      normal range in both sexes. FECa in men returned to the normal level within 3.3
      years from the completion of soil replacement. Overall, it is suggested that the
      renal handling of Ca showed no or only a slight change throughout the observation
      period in both sexes. P-U decreased gradually. P-S showed lower than normal
      values in the men and values at the lower end of the normal range in women,
      although the values recovered gradually to normal. %TRP values remained low
      throughout the observation period and the values did not recover in either sex.
      However, the results of P-U and P-S suggested that the renal handling of P may
      recover after the completion of soil replacement.

PMID- 19089320
TI  - Thyroid storm with atypical neurological signs: an unusual clinical emergence of
      a life-threatening event.

PMID- 19089321
TI  - Effects of loratadine/montelukast on vigilance and alertness task performance in
      a simulated cabin environment.
AB  - INTRODUCTION: Sedating effects of some medications used to treat allergic
      rhinitis (AR) symptoms can impair an individual's ability to function optimally.
      The objective of this study was to characterize the effects of a single dose of
      loratadine/montelukast (L/M) versus placebo and diphenhydramine on daytime
      somnolence and psychomotor performance in healthy volunteers. METHODS: In this
      single-center, randomized, double-blind, placebo- and active-controlled,three-way
      crossover study, healthy volunteers received single doses of placebo, L/M 10
      mg/10 mg, and diphenhydramine 50 mg. Subjects (n=23) were evaluated under
      simulated cabin pressure using the following tools: Vigilance and Tracking Task
      (VigTrack), measuring vigilance and tracking performance; the Multi-Attribute
      Task Battery (MAT), measuring ability to perform multiple tasks simultaneously;
      and the Stanford Sleepiness Scale (SSS), measuring sedative effects of
      medication, at baseline and each hour from 1 to 6 hours postdose. Safety was
      monitored via adverse events and vital signs. RESULTS: Performances on VigTrack
      and MAT from 1 to 6 hours after dosing were not significantly different between
      L/M and placebo groups; in contrast, diphenhydramine resulted in significant
      impairment of tracking for up to 5 hours (P< or =0.01) and vigilance performance
      for up to 3 hours (P< or =0.05) on VigTrack versus placebo. Scores of subjective
      sleepiness as measured by SSS were similar for patients treated with L/M versus
      placebo, whereas significant increases in sleepiness occurred between 1-5 hours
      posttreatment in diphenhydramine-treated patients versus placebo-treated patients
      (P< or =0.05). CONCLUSIONS: L/M is similar to placebo in effects on daytime
      somnolence and psychomotor performance. L/M treatment resulted in significantly
      less sleepiness and impairment of vigilance and tracking than diphenhydramine.

PMID- 19089323
TI  - Biochemistry of soluble guanylate cyclase.
AB  - Nitric oxide (NO) functions in biology as both a critical cytotoxic agent and an
      essential signaling molecule. The toxicity of the diatomic gas has long been
      accepted; however, it was not known to be a signaling molecule until it was
      identified as the endothelium-derived relaxing factor (EDRF). Since this
      discovery, the physiological signaling pathways that are regulated by NO have
      been the focus of numerous studies. Many of the cellular responses that NO
      modulates are mediated by the heme protein soluble guanylate cyclase (sGC). NO
      binds to sGC at a diffusion controlled rate, and leads to a several 100-fold
      increase in the synthesis of the second messenger cGMP from GTP. Other diatomic
      gases either do not bind (dioxygen), or do not significantly activate (carbon
      monoxide) sGC. This provides selectivity and efficiency for NO even in an aerobic
      environment, which is critical due to the high reactivity of NO. Several
      biochemical studies have focused on elucidating the mechanism of NO activation
      and O(2) discrimination. Significant advances in our understanding of these
      topics have occurred with the identification and characterization of the sGC-like
      homologues termed Heme-Nitric oxide and OXygen binding (H-NOX) proteins.

PMID- 19089324
TI  - Genetic mouse models of the NO receptor 'soluble' guanylyl cyclases.
AB  - The NO/cGMP signalling cascade has an important role in smooth muscle relaxation,
      inhibition of platelet aggregation and neuronal transmission. Although the
      function of the main NO receptor GC (NO-GC) is well established, the particular
      tasks of the NO receptor isoforms (NO-GC1 and NO-GC2) are unclear and NO targets
      other than NO-GC have been postulated. Mice deficient in either NO receptor
      isoform or with a complete lack of NO-GC are now available and allow new insights
      in NO/cGMP signalling. The first reports about the KO strains show that, outside
      the neuronal system, the NO-GC isoforms can substitute for each other, and that
      amazingly low cGMP increases are sufficient to induce smooth muscle relaxation.
      In the neuronal system, however, the NO-GC isoforms obviously serve distinct
      functions as both isoforms are required for long term potentiation. Analysis of
      the complete NO-GC KO provides evidence that the vasorelaxing and platelet
      inhibiting effects of NO are solely mediated by NO-GC. Thus, NO-GC appears to be
      the only NO receptor in these two systems.

PMID- 19089322
TI  - A short history of cGMP, guanylyl cyclases, and cGMP-dependent protein kinases.
AB  - Here, we review the early studies on cGMP, guanylyl cyclases, and cGMP-dependent
      protein kinases to facilitate understanding of development of this exciting but
      complex field of research encompassing pharmacology, biochemistry, physiology,
      and molecular biology of these important regulatory molecules.

PMID- 19089325
TI  - Function and dysfunction of mammalian membrane guanylyl cyclase receptors:
      lessons from genetic mouse models and implications for human diseases.
AB  - Besides soluble guanylyl cyclase (GC), the receptor for NO, there are seven
      plasma membrane forms of guanylyl cyclase (GC) receptors, enzymes that synthesize
      the second-messenger cyclic GMP (cGMP). All membrane GCs (GC-A to GC-G) share a
      basic topology, which consists of an extracellular ligand binding domain, a short
      transmembrane region, and an intracellular domain that contains the catalytic
      (GC) region. Although the presence of the extracellular domain suggests that all
      these enzymes function as receptors, specific ligands have been identified for
      only four of them (GC-A through GC-D). GC-A mediates the endocrine effects of
      atrial and B-type natriuretic peptides regulating arterial blood pressure and
      volume homeostasis and also local antihypertrophic and antifibrotic actions in
      the heart. GC-B, the specific receptor for C-type natriuretic peptide, has a
      critical role in endochondral ossification. GC-C mediates the effects of guanylin
      and uroguanylin on intestinal electrolyte and water transport and epithelial cell
      growth and differentiation. GC-E and GC-F are colocalized within the same
      photoreceptor cells of the retina and have an important role in
      phototransduction. Finally, GC-D and GC-G appear to be pseudogenes in the human.
      In rodents, GC-D is exclusively expressed in the olfactory neuroepithelium, with
      chemosensory functions. GC-G is the last member of the membrane GC form to be
      identified. No other mammalian transmembrane GCs are predicted on the basis of
      gene sequence repositories. In contrast to the other orphan receptor GCs, GC-G
      has a broad tissue distribution in rodents, including the lung, intestine,
      kidney, skeletal muscle, and sperm, raising the possibility that there is another
      yet to be discovered family of cGMP-generating ligands. This chapter reviews the
      structure and functions of membrane GCs, with special focus on the insights
      gained to date from genetically modified mice and the role of alterations of
      these ligand/receptor systems in human diseases.

PMID- 19089326
TI  - Phosphodiesterases in the central nervous system.
AB  - Phosphodiesterases (PDEs) represent important cornerstones of cGMP signaling in
      various tissues. Since the discovery of PDE activity in 1962, it has become clear
      that the functional characteristics of PDEs and their role in cyclic nucleotide
      signaling are fairly complex. On the one hand, members of the PDE family
      responsible for the hydrolysis of cGMP affect cellular responses by shaping cGMP
      signals derived from the activation of soluble cytosolic and/or membrane bound
      particulate guanylyl cyclases. Conversely, PDEs may function as downstream
      effectors in the cGMP signaling cascade. To make things even more sophisticated,
      cGMP modulates the activity of several PDEs either directly, by binding to a
      regulatory domain, or indirectly, through phosphorylation, and the result can be
      either inhibition or stimulation of the enzyme, depending on the subtype.
      Furthermore, cross-talk between cGMP and cAMP signaling is achieved by cGMP
      dependent modulation of PDEs hydrolyzing cAMP and vice versa. Mammals possess at
      least 21 PDE genes and often express a set of PDEs in a tissue- and
      differentiation-dependent manner. Given these premises, it is still a challenging
      task to elucidate the physiological function(s) of individual PDE genes. The
      present chapter focuses on the role of PDEs as regulators of neuronal functions.
      Useful information regarding this topic has been gained by studying (1) the
      expression pattern of PDEs in the CNS, (2) the association of PDEs with specific
      macromolecular signaling complexes and (3) the phenotypes associated with
      mutations or ablation of PDE genes in man, mice and fruit flies, respectively.
      PDEs degrading cGMP and/or being regulated by cGMP have been implicated in
      cognition and learning, Parkinson's disease, attention deficit hyperactivity
      disorder, psychosis and depression. Correspondingly, modulators of PDEs have
      become attractive tools for treatment of these disorders of CNS function.

PMID- 19089327
TI  - Structural and biochemical aspects of tandem GAF domains.
AB  - The GAF domain is a small-molecule-binding-domain (SMBD) identified in >7400
      proteins. However, mostly the ligands are unknown. Here we mainly deal with
      regulatory N-terminal tandem GAF domains, GAF-A and GAF-B, of four mammalian
      phosphodiesterases (PDEs) and of two cyanobacterial adenylyl cyclases (ACs) which
      bind cyclic nucleotides. These tandem GAFs are preceded by N-terminal sequences
      of variable lengths and a function of their own. In mammals, GAF domains are
      found only in cyclic nucleotide PDEs 2, 5, 6, 10, and 11. cAMP is the ligand for
      phosphodiesterase 10, cGMP for the others. Two cyanobacterial ACs, CyaB1 and 2,
      carry regulatory cAMP-binding tandem GAF domains which are similar in sequence to
      the mammalian ones. These tandem GAF domains have a prominent NKFDE motif which
      contributes to ligand binding in an as yet unknown manner. Contradicting
      structures (parallel vs. antiparallel) are available for the tandem GAF domains
      of PDE 2 and AC CyaB2. In addition, the structures of phosphodiesterase 5 and 10
      GAF monomers with bound ligands have been solved. In all instances, cyclic
      nucleotide binding involves specific protein-ligand interactions within a tightly
      closed binding pocket and minimal solvent exposure of the ligand. The PDE tandem
      GAF domains can functionally substitute for the tandem of the cyanobacterial AC
      CyaB1; e.g. cGMP-regulation is grafted onto the AC using tandem GAFs from PDEs 2,
      5 and 11. Studies of GAF domain-regulated PDEs are hampered by the identities of
      regulator and substrate molecules. Using AC CyaB1 as a reporter which uses ATP as
      a substrate solves this issue and makes the tandem GAF domains of mammalian PDEs
      available for detailed kinetic and mechanistic studies. In addition, drugs which
      potentially act on PDE regulatory domains may be assayed with such a novel test
      system.

PMID- 19089328
TI  - Cyclic nucleotide-gated channels.
AB  - Cyclic nucleotide-gated (CNG) channels are ion channels which are activated by
      the binding of cGMP or cAMP. The channels are important cellular switches which
      transduce changes in intracellular concentrations of cyclic nucleotides into
      changes of the membrane potential and the Ca2+ concentration. CNG channels play a
      central role in the signal transduction pathways of vision and olfaction.
      Structurally, the channels belong to the superfamily of pore-loop cation
      channels. They share a common domain structure with hyperpolarization-activated
      cyclic nucleotide-gated (HCN) channels and Eag-like K+ channels. In this chapter,
      we give an overview on the molecular properties of CNG channels and describe the
      signal transduction pathways these channels are involved in. We will also
      summarize recent insights into the physiological and pathophysiological role of
      CNG channel proteins that have emerged from the analysis of CNG channel-deficient
      mouse models and human channelopathies.

PMID- 19089329
TI  - cGMP regulated protein kinases (cGK).
AB  - cGMP-dependent protein kinases (cGK) are serine/threonine kinases that are widely
      distributed in eukaryotes. Two genes--prkg1 and prkg2--code for cGKs, namely cGKI
      and cGKII. In mammals, two isozymes, cGKIalpha and cGKIbeta, are generated from
      the prkg1 gene. The cGKI isozymes are prominent in all types of smooth muscle,
      platelets, and specific neuronal areas such as cerebellar Purkinje cells,
      hippocampal neurons, and the lateral amygdala. The cGKII prevails in the
      secretory epithelium of the small intestine, the juxta-glomerular cells, the
      adrenal cortex, the chondrocytes, and in the nucleus suprachiasmaticus. Both cGKs
      are major downstream effectors of many, but not all signalling events of the
      NO/cGMP and the ANP/cGMP pathways. cGKI relaxes smooth muscle tone and prevents
      platelet aggregation, whereas cGKII inhibits renin secretion, chloride/water
      secretion in the small intestine, the resetting of the clock during early night,
      and endochondreal bone growth. cGKs are also modulators of cell growth and many
      other functions.

PMID- 19089330
TI  - cGK substrates.
AB  - Signalling of cGK (cGMP-dependent protein kinases) are mediated through
      phosphorylation of specific substrates. Several substrates of cGKI and cGKII were
      identified meanwhile. Some cGKI substrates are specifically regulated by the
      cGKIalpha or the cGKIbeta isozyme. In various cells and tissues, different cGK
      substrates exist that are essential for the regulation of diverse functions
      comprising tissue contractility, cell motility, cell contact, cellular secretion,
      cell proliferation, and cell differentiation. On the molecular level, cGKI
      substrates fulfill various cellular functions regulating e.g. the intracellular
      calcium and potassium concentration, the calcium sensitivity, and the
      organisation of the intracellular cytoskeleton. cGKII substrates are involved
      e.g. in chloride transport, sodium/proton transport and transcriptional
      regulation. The understanding of cGK signalling and function depends strongly on
      the identification of further specific substrates. In the last years, diverse
      approaches ranging from biochemistry to genetic deletion lead to the
      identification and establishment of several substrates, which raised new insights
      in the molecular mechanisms of cGK functions and elucidated new cellular cGK
      functions. However, the analysis of the dynamic signalling of cGK in tissues and
      cells will be necessary to discover new signalling pathways and substrates.

PMID- 19089331
TI  - Biochemical Detection of cGMP From Past to Present: An Overview.
AB  - Cyclic guanosine monophosphate (cGMP), generated via the guanylate cyclase (GC)
      catalyzed conversion from GTP, is unequivocally recognized as crucial second
      messenger, intimately involved in the regulation of a broad range of
      physiological processes such as long term potentiation, blood pressure
      regulation, or platelet aggregation (for review: Hobbs 2000). Since its first
      identification in rat urine by Ashman and co-workers (1963), various approaches
      have been conceived and established to quantify cGMP in biological samples, or to
      detect cGMP as the reaction product of enzymatic assays, allowing the
      determination of kinetic parameters. These approaches have evolved from laborious
      handling of small numbers of samples with average sensitivity to highly developed
      biochemical detection assays allowing the processing of very large numbers of
      samples. The present article focuses upon the history of biochemical cGMP
      detection from the pioneering work of the early years to the actual state-of-the
      art approaches for the detection of this important biological messenger.

PMID- 19089332
TI  - Novel techniques for real-time monitoring of cGMP in living cells.
AB  - Recent developments of biophysical and electrophysiological techniques have
      enabled researchers to monitor levels of free intracellular cGMP in real-time and
      in intact living cells. These techniques are based on the use of cGMP sensors,
      which respond to cGMP with changes in transmembrane ion current or changes in
      fluorescence. Here, we describe the principles of these techniques, compare them
      in terms of sensitivity and discuss possible application for current cell biology
      and physiology.

PMID- 19089333
TI  - NO and sGC-stimulating NO donors.
AB  - Our knowledge of nitric oxide (NO) as a crucial endogenous signalling molecule
      continues to expand. Many, but not all, of the actions of NO are mediated by
      activation of soluble guanylyl cyclase (sGC) in target tissues. The aim of this
      chapter is to encapsulate the functions of NO in mammalian biology, tied to the
      chemistry of this unusual signalling entity. The experimental usefulness and
      therapeutic potential of the most widely utilised NO donor drugs is reviewed,
      with special consideration given to the importance of choosing the correct NO
      donor for any given experiment, in vitro, in vivo or in clinical studies.

PMID- 19089334
TI  - NO-independent, haem-dependent soluble guanylate cyclase stimulators.
AB  - The nitric oxide (NO) signalling pathway is altered in cardiovascular diseases,
      including systemic and pulmonary hypertension, stroke, and atherosclerosis. The
      vasodilatory properties of NO have been exploited for over a century in
      cardiovascular disease, but NO donor drugs and inhaled NO are associated with
      significant shortcomings, including resistance to NO in some disease states, the
      development of tolerance during long-term treatment, and non-specific effects
      such as post-translational modification of proteins. The development of
      pharmacological agents capable of directly stimulating the NO receptor, soluble
      guanylate cyclase (sGC), is therefore highly desirable. The benzylindazole
      compound YC-1 was the first sGC stimulator to be identified; this compound formed
      a lead structure for the development of optimized sGC stimulators with improved
      potency and specificity for sGC, including CFM-1571, BAY 41-2272, BAY 41-8543,
      and BAY 63-2521. In contrast to the NO- and haem-independent sGC activators such
      as BAY 58-2667, these compounds stimulate sGC activity independent of NO and also
      act in synergy with NO to produce anti-aggregatory, anti-proliferative, and
      vasodilatory effects. Recently, aryl-acrylamide compounds were identified
      independent of YC-1 as sGC stimulators; although structurally dissimilar to YC-1,
      they have a similar mode of action and promote smooth muscle relaxation.
      Pharmacological stimulators of sGC may be beneficial in the treatment of a range
      of diseases, including systemic and pulmonary hypertension, heart failure,
      atherosclerosis, erectile dysfunction, and renal fibrosis. An sGC stimulator, BAY
      63-2521, is currently in clinical development as an oral therapy for patients
      with pulmonary hypertension. It has demonstrated efficacy in a proof-of-concept
      study, reducing pulmonary vascular resistance and increasing cardiac output from
      baseline. A full, phase 2 trial of BAY 63-2521 in pulmonary hypertension is
      underway.

PMID- 19089335
TI  - NO- and haem-independent soluble guanylate cyclase activators.
AB  - Oxidative stress, a risk factor for several cardiovascular disorders, interferes
      with the NO/sGC/cGMP signalling pathway through scavenging of NO and formation of
      the strong intermediate oxidant, peroxynitrite. Under these conditions,
      endothelial and vascular dysfunction develops, culminating in different cardio
      renal and pulmonary-vascular diseases. Substituting NO with organic nitrates that
      release NO (NO donors) has been an important principle in cardiovascular therapy
      for more than a century. However, the development of nitrate tolerance limits
      their continuous clinical application and, under oxidative stress and increased
      formation of peroxynitrite foils the desired therapeutic effect. To overcome
      these obstacles of nitrate therapy, direct NO- and haem-independent sGC
      activators have been developed, such as BAY 58-2667 (cinaciguat) and HMR1766
      (ataciguat), showing unique biochemical and pharmacological properties. Both
      compounds are capable of selectively activating the oxidized/haem-free enzyme via
      binding to the enzyme's haem pocket, causing pronounced vasodilatation. The
      potential importance of these new drugs resides in the fact that they selectively
      target a modified state of sGC that is prevalent under disease conditions as
      shown in several animal models and human disease. Activators of sGC may be
      beneficial in the treatment of a range of diseases including systemic and
      pulmonary hypertension (PH), heart failure, atherosclerosis, peripheral arterial
      occlusive disease (PAOD), thrombosis and renal fibrosis. The sGC activator
      HMR1766 is currently in clinical development as an oral therapy for patients with
      PAOD. The sGC activator BAY 58-2667 has demonstrated efficacy in a proof-of
      concept study in patients with acute decompensated heart failure (ADHF), reducing
      pre- and afterload and increasing cardiac output from baseline. A phase IIb
      clinical study for the indication of ADHF is currently underway.

PMID- 19089337
TI  - Cyclic GMP-hydrolyzing phosphodiesterases.

PMID- 19089338
TI  - cGMP-dependent protein kinase modulators.
AB  - The first cGMP-dependent protein kinase (PKG) modulators were described nearly 30
      years ago and since then more than 200 compounds have been synthesized and
      tested, but only a small subset of these compounds has found widespread
      application. The aim of this review is to suggest a framework for evaluating and
      using PKG activators and inhibitors and to explore and interpret PKG signal
      transduction in cell culture-based model systems. Therefore, cross-reactivity of
      cGMP-analogs with other classes of cyclic nucleotide binding proteins, as well as
      the advantages and problems of newly designed PKG inhibitors, are discussed.
      Additional information and a search option are available at www.cyclic
      nucleotides.org

PMID- 19089336
TI  - Natriuretic peptides: their structures, receptors, physiologic functions and
      therapeutic applications.
AB  - Natriuretic peptides are a family of three structurally related hormone/
      paracrine factors. Atrial natriuretic peptide (ANP) and B-type natriuretic
      peptide (BNP) are secreted from the cardiac atria and ventricles, respectively.
      ANP signals in an endocrine and paracrine manner to decrease blood pressure and
      cardiac hypertrophy. BNP acts locally to reduce ventricular fibrosis. C-type
      natriuretic peptide (CNP) primarily stimulates long bone growth but likely serves
      unappreciated functions as well. ANP and BNP activate the transmembrane guanylyl
      cyclase, natriuretic peptide receptor-A (NPR-A). CNP activates a related cyclase,
      natriuretic peptide receptor-B (NPR-B). Both receptors catalyze the synthesis of
      cGMP, which mediates most known effects of natriuretic peptides. A third
      natriuretic peptide receptor, natriuretic peptide receptor-C (NPR-C), clears
      natriuretic peptides from the circulation through receptor-mediated
      internalization and degradation. However, a signaling function for the receptor
      has been suggested as well. Targeted disruptions of the genes encoding all
      natriuretic peptides and their receptors have been generated in mice, which
      display unique physiologies. A few mutations in these proteins have been reported
      in humans. Synthetic analogs of ANP (anaritide and carperitide) and BNP
      (nesiritide) have been investigated as potential therapies for the treatment of
      decompensated heart failure and other diseases. Anaritide and nesiritide are
      approved for use in acute decompensated heart failure, but recent studies have
      cast doubt on their safety and effectiveness. New clinical trials are examining
      the effect of nesiritide and novel peptides, like CD-NP, on these critical
      parameters. In this review, the history, structure, function, and clinical
      applications of natriuretic peptides and their receptors are discussed.

PMID- 19089339
TI  - cGMP-dependent protein kinase as a modifier of behaviour.
AB  - The importance of cGMP-dependent protein kinase (PKG) to the modulation of
      behavioural phenotypes has become increasingly clear in recent decades. The
      effects of PKG on behaviour have been studied in diverse taxa from perspectives
      as varied as ethology, evolution, genetics and neuropharmacology. The genetic
      variation of the Drosophila melanogaster gene, foraging (for), has provided a
      fertile model for examining natural variation in a single major gene influencing
      behaviour. Concurrent studies in other invertebrates and mammals suggest that PKG
      is an important signalling molecule with varied influences on behaviour and a
      large degree of pleiotropy and plasticity. Comparing these cross-taxa effects
      suggests that there are several potentially overlapping behavioural modalities in
      which PKG signalling acts to influence behaviours which include feeding,
      learning, stress and biological rhythms. More in-depth comparative analyses
      across taxa of the similarities and differences of the influence of PKG on
      behaviour may provide powerful mechanistic explications of the evolution of
      behaviour.

PMID- 19089340
TI  - cGMP in the vasculature.
AB  - Cyclic guanosine 3', 5'-monophosphate (cGMP) plays an integral role in the
      control of vascular function. Generated from guanylate cyclases in response to
      the endogenous ligands, nitric oxide (NO) and natriuretic peptides (NPs), cGMP
      influences a number of vascular cell types and regulates vasomotor tone,
      endothelial permeability, cell growth and differentiation, as well as platelet
      and blood cell interactions. Reciprocal regulation of the NO-cGMP and NP-cGMP
      pathways is evident in the vasculature such that one cGMP generating system may
      compensate for the dysfunction of the other. Indeed, aberrant cGMP production
      and/or signalling accompanies many vascular disorders such as hypertension,
      atherosclerosis, coronary artery disease and diabetic complications. This chapter
      highlights the main vascular functions of cGMP, its role in disease and the
      resulting current and potential therapeutic applications. With respect to
      pulmonary hypertension, heart failure and erectile dysfunction, as well as cGMP
      signal transduction, the reader is specifically referred to other dedicated
      chapters.

PMID- 19089341
TI  - Modulating cGMP to treat lung diseases.
AB  - BACKGROUND: Nitric oxide (NO) is constitutively produced in the lung by NO
      synthases. The main cellular sources of lung NO production are the vascular
      endothelium and the airway epithelia (Bohle et al. 2000; German et al. 2000; Ide
      et al. 1999). Local NO production contributes to regulation of pulmonary
      perfusion depending on alveolar ventilation to assure optimized
      ventilation/perfusion distribution (Grimminger et al. 1995). NO-synthase activity
      is regulated on transcriptional and post-translational redox-based modulation
      level. The common signaling pathway of endogenous vasodilators, such as nitric
      oxide, prostaglandins, and natriuretic peptides, engage cyclic nucleotides (cAMP
      and cGMP). These second messengers are mainly produced by activation of adenylate
      and guanylate-cyclases, both membrane-bound and soluble (Beavo 1995).
      Phosphodiesterases (PDEs) represent a superfamily of enzymes, with PDE1 through
      PDE11 being currently known, that inactivate cyclic AMP and cyclic GMP, with
      different tissue distribution and substrate specificities (Ahn et al. 1991; Von
      Euler and Liljestrand. 1946). Because of stabilization of these second
      messengers, PDE inhibitors differentially regulate levels of cAMP and/or cGMP,
      depending on their selectivity profile. Recently, direct activators and
      stimulators of the sGC have been suggested as new therapeutic tools for the
      treatment of lung vascular disorders that might have even higher potency than PDE
      inhibitors or exogenously applied NO.

PMID- 19089343
TI  - Erectile dysfunction and lower urinary tract.
AB  - During the last decades it turned out that the NO/cGMP signaling cascade is one
      of the most prominent regulators of a variety of physiological and
      pathophysiological processes in a broad range of mammalian tissues. Thus cGMP is
      a key second messenger and targeting this pathway by increasing intracellular
      cGMP levels is a very successful approach in pharmacology as shown for nitrates,
      PDE5 inhibitors and more recently for stimulators of the guanylate cyclase.
      Besides the beneficial effects of cGMP elevation in cardiac, vascular, pulmonary,
      renal or liver disorders the launch of PDE5 inhibitors for the treatment of
      erectile dysfunction 10 years ago, has directed a lot of attention to the NO/cGMP
      signaling in the lower urinary tract. Triggered by the use of PDE5 inhibitors in
      ED it turned out that cGMP is a common regulatory mechanism for lower urinary
      tract function also beyond ED. In recent years intense research and development
      efforts were undertaken to elucidate the role of the NO/cGMP and to fully exploit
      the therapeutic implications of cGMP elevation in urological disorders in ED and
      beyond. Therefore we have summarized the effects of cGMP elevation for treatment
      of erectile dysfunction in males and in females. We have also reviewed the recent
      pre-clinical and clinical lines of evidence for treatment options of benign
      prostatic hyperplasia and lower urinary tract symptoms in male patients and
      overactive bladder and urinary incontinence in female patients. In addition we
      also touch more speculative concepts using cGMP elevating drugs for the treatment
      of premature ejaculation, peyornies disease and stone disease.

PMID- 19089342
TI  - Modulation of cGMP in heart failure: a new therapeutic paradigm.
AB  - Heart failure (HF) is a common disease that continues to be associated with high
      morbidity and mortality warranting novel therapeutic strategies. Cyclic guanosine
      monophosphate (cGMP) is the second messenger of several important signaling
      pathways based on distinct guanylate cyclases (GCs) in the cardiovascular system.
      Both the nitric oxide/soluble GC (NO/sGC) as well as the natriuretic peptide/GC-A
      (NP/GC-A) systems are disordered in HF, providing a rationale for their
      therapeutic augmentation. Soluble GC activation with conventional
      nitrovasodilators has been used for more than a century but is associated with
      cGMP-independent actions and the development of tolerance, actions which novel NO
      independent sGC activators now in clinical development lack. Activation of GC-A
      by administration of naturally occurring or designer natriuretic peptides is an
      emerging field, as is the inhibition of enzymes that degrade endogenous NPs.
      Finally, inhibition of cGMP-degrading phosphodiesterases, particularly
      phosphodiesterase 5 provides an additional strategy to augment cGMP-signaling.

PMID- 19089344
TI  - cGMP and cGMP-dependent protein kinase in platelets and blood cells.
AB  - Platelets are specialized adhesive cells that play a key role in normal and
      pathological hemostasis through their ability to rapidly adhere to subendothelial
      matrix proteins (platelet adhesion) and to other activated platelets (platelet
      aggregation). NO plays a crucial role in preventing platelet adhesion and
      aggregation. In platelets, cGMP synthesis is catalyzed by sGC, whereas PDE2, PDE3
      and PDE5 are responsible for cGMP degradation. Stimulation of cGK by cGMP leads
      to phosphorylation of multiple target substrates. These substrates inhibit
      elevation of intracellular calcium, integrin activation, cytoskeletal
      reorganization, and platelet granule secretion, events normally associated with
      platelet activation. The NO/cGMP pathway also plays a significant role in many
      other blood cell types in addition to platelets. In leukocytes, depending on the
      specific cell type, cGMP signaling regulates gene expression, differentiation,
      migration, cytokine production, and apoptosis.

PMID- 19089345
TI  - cGMP signalling in the mammalian brain: role in synaptic plasticity and
      behaviour.
AB  - The second messenger cyclic guanosine 3',5'-monophosphate (cGMP) plays a crucial
      role in the control of cardiovascular and gastrointestinal homeostastis, but its
      effects on neuronal functions are less established. This review summarizes recent
      biochemical and functional data on the role of the cGMP signalling pathway in the
      mammalian brain, with a focus on the regulation of synaptic plasticity, learning,
      and other complex behaviours. Expression profiling, along with pharmacological
      and genetic manipulations, indicates important functions of nitric oxide (NO)
      sensitive soluble guanylyl cyclases (sGCs), cGMP-dependent protein kinases
      (cGKs), and cGMP-regulated phosphodiesterases (PDEs) as generators, effectors,
      and modulators of cGMP signals in the brain, respectively. In addition, neuronal
      cGMP signalling can be transmitted through cyclic nucleotide-gated (CNG) or
      hyperpolarization-activated cyclic nucleotide-gated (HCN) ion channels. The
      canonical NO/sGC/cGMP/cGK pathway modulates long-term changes of synaptic
      activity in the hippocampus, amygdala, cerebellum, and other brain regions, and
      contributes to distinct forms of learning and memory, such as fear conditioning,
      motor adaptation, and object recognition. Behavioural studies indicate that cGMP
      signalling is also involved in anxiety, addiction, and the pathogenesis of
      depression and schizophrenia. At the molecular level, different cGK isoforms
      appear to mediate effects of cGMP on presynaptic transmitter release and
      postsynaptic functions. The cGKs have been suggested to modulate cytoskeletal
      organization, vesicle and AMPA receptor trafficking, and gene expression via
      phosphorylation of various substrates including VASP, RhoA, RGS2, hSERT, GluR1, G
      substrate, and DARPP-32. These and other components of the cGMP signalling
      cascade may be attractive new targets for the treatment of cognitive impairment,
      drug abuse, and psychiatric disorders.

PMID- 19089346
TI  - Derivation and manipulation of murine embryonic stem cells.
AB  - Pluripotent embryonic stem (ES) cell lines were first isolated over 25 years ago
      and remain an essential tool in molecular and developmental biology to this day.
      In particular, the use of homologous recombination and subsequent generation of
      ES-derived mice has greatly facilitated research across all fields. Moreover, ES
      cells represent an extremely attractive model to study events in early
      development. In this chapter, we will describe the derivation and propagation of
      murine ES cells. This is followed by a description of targeting ES cells and a
      protocol for the generation of mice by diploid and tetraploid blastocyst
      injections.

PMID- 19089347
TI  - Patterning mouse and human embryonic stem cells using micro-contact printing.
AB  - Local micro-environmental cues consisting of soluble cytokines, extra-cellular
      matrix (ECM), and cell-cell contacts are determining factors in stem cell fate.
      These extrinsic cues form a 'niche' that governs a stem cell's decision to either
      self-renew or differentiate into one or more cell types. Recently, it has been
      shown that micro-patterning stem cells in two- and three-dimensions can provide
      direct control over several parameters of the local micro-environment, including
      colony size, distance between colonies, ECM substrate, and homotypic or
      heterotypic cell-cell contact. The protocol described here uses micro-contact
      printing to pattern ECM onto tissue culture substrates. Cells are seeded onto the
      patterned substrates in serum-free media and are confined to the patterned
      features. After patterning, stem cell phenotype is analyzed using quantitative
      immunocytochemistry and immunohistochemistry.

PMID- 19089348
TI  - Efficient gene knockdowns in human embryonic stem cells using lentiviral-based
      RNAi.
AB  - Human embryonic stem cells (hESCs) represent a powerful platform to study human
      development and its dysfunction in human disease. However, certain biological
      properties have hampered the application of standard gain of function and loss of
      function tools to these cells. For example, while traditional gene knockouts by
      homologous recombination (HR) have been reported, the low cloning efficiency of
      hESCs has made HR a lengthy and laborious undertaking. An alternative method of
      achieving loss of function is the use of small interfering RNAs (siRNAs) that can
      be introduced either as pre-synthesized duplexed oligonucleotides or via
      lentiviral vector. The use of a lentiviral vector to deliver siRNAs has proven to
      be a rapid and specific way to achieve highly efficient and persistent gene
      knockdowns in hESCs. In this chapter, we will summarize the key requirements for
      the successful application of lentiviral RNAi in hESCs.

PMID- 19089349
TI  - Measurement of cell-penetrating peptide-mediated transduction of adult
      hematopoietic stem cells.
AB  - The ability of cell-penetrating peptides (CPPs) to cross cell membranes and
      transport cargo into cells makes them an attractive tool for the molecular
      engineering of stem cells. Even though the exact mechanism of transduction
      remains unclear, their potential has been demonstrated for diverse applications,
      including hematopoietic stem cell expansion and the generation of islets cells
      from embryonic stem cells. Several parameters can affect the intracellular
      delivery of CPP-based constructs. Those include the type of cells targeted, the
      type of CPP used, and the properties of the cargo. For this reason, it is
      important to have a means to quantitatively assess the transduction efficiency of
      specific constructs in the cell type of interest in order to select the best
      vector for a specific application. In this chapter, we describe a method to
      measure the uptake of HIV transactivator of transcription (TAT) and the homeobox
      protein Antennapedia (Antp) constructs in primary hematopoietic progenitor cells
      and hematopoietic cell lines. This method is useful to compare, select, and
      optimize different strategies to deliver CPP-based constructs into a given cell
      type.

PMID- 19089350
TI  - Stem cell sources for regenerative medicine.
AB  - Tissue-resident stem cells or primitive progenitors play an integral role in
      homeostasis of most organ systems. Recent developments in methodologies to
      isolate and culture embryonic and somatic stem cells have many new applications
      poised for clinical and preclinical trials, which will enable the potential of
      regenerative medicine to be realized. Here, we overview the current progress in
      therapeutic applications of various stem cells and discuss technical and social
      hurdles that must be overcome for their potential to be realized.

PMID- 19089351
TI  - Investigating the interactions between haemopoietic stem cells and their niche:
      methods for the analysis of stem cell homing and distribution within the marrow
      following transplantation.
AB  - Interactions between haemopoietic stem cells (HSC) and their microenvironment
      serve multiple functions including the attraction to and retention and regulation
      in the bone marrow HSC niche. However, the cell adhesion molecules involved,
      their HSC receptors and the mechanisms underpinning these processes remain poorly
      understood. An ability to thoroughly investigate the roles of specific molecules
      in this process relies on a variety of in vitro and in vivo assays including the
      assessment of a HSC ability to home to the bone marrow and analysis of its
      lodgement within the bone marrow.

PMID- 19089352
TI  - Ex vivo megakaryocyte expansion and platelet production from human cord blood
      stem cells.
AB  - The identification and cloning of thrombopoietin was certainly a defining moment
      for the study of megakaryopoiesis and thrombopoiesis ex vivo. This and other
      progresses made in the development of culture processes for hematopoietic stem
      cells have paved the way for ongoing clinical trials and, in the future, for the
      potential therapeutic use of ex vivo produced blood substitutes such as
      platelets. This chapter describes a 14-day culture protocol for the production of
      megakaryocytes (MK) and platelets from human cord blood stem cells. The CD34+
      cells are grown in a serum-free medium supplemented with a newly developed
      cytokine cocktail optimizing MK differentiation, expansion, and maturation. A
      detailed methodology for flow cytometry analysis of the cells and platelets is
      also presented together with supporting figures. A brief review on megakaryocytic
      differentiation and ex vivo MK cultures is first presented.

PMID- 19089353
TI  - Ex vivo generation of human red blood cells: a new advance in stem cell
      engineering.
AB  - We describe a technological approach permitting the massive expansion of CD34(+)
      stem cells and their 100% conversion ex vivo into mature red blood cells (RBC).
      The protocol comprises three steps: a first step consisting of cell proliferation
      and induction of erythroid differentiation in a liquid medium without serum in
      the presence of growth factors (GF), a second based on a model reconstitution of
      the medullar microenvironment (ME) (human MSC or murine stromal cells) in the
      presence of GF, and a third in the presence of the ME alone, without any GF. This
      work highlights the impact of the ex vivo microenvironment on the terminal
      maturation of erythroid cells. A critical point is that the RBC generated in
      vitro have all the characteristics of functional native adult RBC. Moreover, this
      new concept of 'cultured RBC' (cRBC) is important for basic research into
      terminal erythropoiesis and has major clinical implications, especially in
      transfusion medicine. The three-step protocol can be adapted to use hematopoietic
      stem cells (HSC) from diverse sources: peripheral blood, bone marrow or cord
      blood.

PMID- 19089354
TI  - Isolation and manipulation of mammalian neural stem cells in vitro.
AB  - Neural stem cells are potentially a source of cells not only for replacement
      therapy but also as drug vectors, bringing bioactive molecules into the brain.
      Stem cell-like cells can be isolated readily from the human brain, thus, it is
      important to find culture systems that enable expansion in a multipotent state to
      generate cells that are of potential use for therapy. Currently, two systems have
      been described for the maintenance and expansion of multipotent progenitors, an
      adhesive substrate bound and the neurosphere culture. Both systems have pros and
      cons, but the neurosphere may be able to simulate the three-dimensional
      environment of the niche in which the cells reside in vivo. Thus, the
      neurosphere, when used and cultured appropriately, can expand and provide
      important information about the mechanisms that potentially control neural stem
      cells in vivo.

PMID- 19089355
TI  - Isolation, expansion, and differentiation of mouse skin-derived precursors.
AB  - The isolation and experimental manipulation of multipotent precursors is of
      increasing therapeutic relevance. We recently reported the generation of cultures
      of Skin-derived Precursors ('SKPs'), multipotent cells that can be isolated from
      the dermis of embryonic, neonatal, and adult rodent skin (1), and from adult
      human skin (2) SKPs have similarities to stem cells of the embryonic neural crest
      (3), and differentiate into a variety of neural and mesodermal cell phenotypes,
      including peripheral neurons and glial cells, smooth muscle cells, bone,
      cartilage, and adipocytes (3-5). Here, we detail the establishment, propagation,
      neural differentiation, and immunocytochemical analysis of SKP cultures.

PMID- 19089356
TI  - Xenotransplantation of embryonic stem cell-derived motor neurons into the
      developing chick spinal cord.
AB  - A growing number of specific cell types have been successfully derived from
      embryonic stem cells (ES cells), including a variety of neural cells. In vitro
      generated cells need to be extensively characterized to establish functional
      equivalency with their in vivo counterparts. The ultimate test for the ability of
      ES cell-derived neurons to functionally integrate into neural networks is
      transplantation into the developing central nervous system, a challenging
      technique limited by the poor accessibility of mammalian embryos. Here we
      describe xenotransplantation of mouse embryonic stem cell-derived motor neurons
      into the developing chick neural tube as an alternative for testing the ability
      of in vitro generated neurons to survive, integrate, extend axons, and form
      appropriate synaptic contacts with functionally relevant targets in vivo. Similar
      methods can be adapted to study functionality of other mammalian cells, including
      derivatives of human ES cells.

PMID- 19089357
TI  - Transplantation of neural stem/progenitor cells into developing and adult CNS.
AB  - Neural transplantation has been a long-standing goal for the treatment of
      neurological injury and disease. The recent discovery of persistent pools of
      neural stem cells within the adult mammalian brain has re-ignited interest in
      transplant therapeutics. Since neural stem cells are self-renewing, it may be
      possible to culture and expand neural stem cells and their progenitor cell
      progeny to sufficient numbers for use in autologous, self-repair strategies. Such
      approaches will require optimized cultivation protocols, as well as extensive
      testing of candidate donor cells to assess their capacity for engraftment,
      survival, and integration. In this chapter, we describe the transplantation of
      neural stem/progenitor cells-cultivated as either neurospheres or neurogenic
      astrocyte monolayers-into the persistently neurogenic olfactory bulb system of
      the adult mouse forebrain, and into the cerebellum of neonatal mutant mice.

PMID- 19089358
TI  - Transplantation of embryonic stem cell-derived dopaminergic neurons in MPTP
      treated monkeys.
AB  - One of the target diseases of cell-replacement therapy is Parkinson's disease.
      Clinical experiences with fetal dopaminergic cell graft have shown that the
      therapy is effective, but limited and accompanied by side effects, such as
      dyskinesia. So, the therapy needs to be further improved and sophisticated.
      Embryonic stem (ES) cells are expected to be another donor cell for the
      treatment, because of its proliferative and differentiation capacities. For
      clinical application, experiments using non-human primates are important, because
      size, anatomy, and biological characteristics of the brain are different between
      rodents and primates. Here, we would like to discuss induction of dopaminergic
      neurons from monkey ES cells and cell transplantation into the brain of monkey
      Parkinson's disease model.

PMID- 19089359
TI  - Isolation and culture of epithelial stem cells.
AB  - In the skin, epithelial stem cells in the hair follicle contribute not only to
      the generation of a new hair follicle with each hair cycle, but also to the
      repair of the epidermis during wound healing. When these stem cells are isolated
      and expanded in culture, they can give rise to hair follicles, sebaceous glands,
      and epidermis when combined with dermis and grafted back onto Nude mice. In this
      chapter, we provide a method for isolating hair follicle epithelial stem cells
      from the skin of adult mice using immunofluorescent labeling to allow for the
      specific purification of epithelial stem cells by fluorescence-activated cell
      sorting (FACS). Notably, this method relies exclusively on cell surface markers,
      making it suitable for use with any strain of mouse and at various stages of the
      hair cycle. We also provide a detailed protocol for culturing epithelial stem
      cells isolated by FACS, allowing for analysis using a wide variety of culture
      assays. Additionally, we provide notes on using cultured cells for specific
      applications, such as viral manipulation and grafting. These techniques should be
      useful for directly evaluating stem cell function in normal mice and in mice with
      skin defects.

PMID- 19089360
TI  - Regeneration of skin and cornea by tissue engineering.
AB  - Progress in tissue engineering has led to the development of technologies
      allowing the reconstruction of autologous tissues from the patient's own cells.
      Thus, tissue-engineered epithelial substitutes produced from cultured skin
      epithelial cells undergo long-term regeneration after grafting, indicating that
      functional stem cells were preserved during culture and following grafting.
      However, these cultured epithelial sheets reconstruct only the upper layer of the
      skin and lack the mechanical properties associated to the connective tissue of
      the dermis. We have designed a reconstructed skin entirely made from human
      cutaneous cells comprising both the dermis and the epidermis, as well as a well
      organized basement membrane by a method named the self-assembly approach. In this
      chapter, protocols to generate reconstructed skin and corneal epithelium suitable
      for grafting are described in details. The methods include extraction and culture
      of human skin keratinocytes, human skin fibroblasts as well as rabbit and human
      corneal epithelial cells, and a complete description of the skin reconstructed by
      the self-assembly approach and of corneal epithelium reconstructed over a fibrin
      gel.

PMID- 19089361
TI  - Prospective isolation of mesenchymal stem cells from mouse compact bone.
AB  - Bone marrow from numerous species, including rodents and man, has been shown to
      contain a rare population of cells known as marrow stromal cells or mesenchymal
      stem cells (MSC). Given the innate ability of these cells to give rise to
      multiple tissue types including bone, fat and cartilage, there is considerable
      interest in utilizing MSC in a broad repertoire of cell-based therapies for the
      treatment of human disease. In order for such therapies to be realized, a
      preclinical animal model in which to refine strategies utilizing MSC is
      required.We have described methodology allowing for the prospective isolation by
      fluorescence activated cell sorting (FACS) of a highly purified population of MSC
      from murine compact bone (CB). These cells are multipotent and capable of
      extensive proliferation in vitro and thus represent an ideal source of cells with
      which to explore both the fundamental biology of MSC and their efficacy in a
      variety of cellular therapies.

PMID- 19089362
TI  - Isolation, propagation, and characterization of human umbilical cord perivascular
      cells (HUCPVCs).
AB  - Current sources of mesenchymal cells, including bone marrow, fat and muscle, all
      require invasive procurement procedures, and provide relatively low frequencies
      of progenitors. Here, we describe the non-invasive isolation, and
      characterization, of a rich source of mesenchymal progenitor cells, which we call
      human umbilical cord perivascular cells (HUCPVCs). HUCPVCs show a similar
      immunological phenotype to bone marrow-derived mesenchymal stromal cells (BM
      MSCs), since they are non-alloreactive, exhibit immunosuppression, and
      significantly reduce lymphocyte activation, in vitro. They present a non
      hematopoietic myofibroblastic mesenchymal phenotype (CD45-, CD34-, CD105+, CD73+,
      CD90+, CD44+, CD106+, 3G5+, CD146+); with a 1:300 frequency at harvest, a short
      doubling time, and a clonogenic frequency of >1:3 in culture. Furthermore, in
      addition to robust quinti-potential differentiation capacity in vitro, HUCPVCs
      have been shown to contribute to both musculo-skeletal and dermal wound healing
      in vivo.

PMID- 19089363
TI  - Bone marrow-derived mesenchymal stem cells: isolation, expansion,
      characterization, viral transduction, and production of conditioned medium.
AB  - Mesenchymal stem cells (MSCs) are defined as self-renewing and multipotent cells
      capable of differentiating into multiple cell types, including osteocytes,
      chondrocytes, adipocytes, hepatocytes, myocytes, neurons, and cardiomyocytes.
      MSCs were originally isolated from the bone marrow stroma but they have recently
      been identified also in other tissues, such as fat, epidermis, and cord blood.
      Several methods have been used for MSC isolation. The most common method is based
      on the ability of the MSCs to selectively adhere to plastic surfaces. Phenotypic
      characterization of MSCs is usually carried out using immunocytochemical
      detection or fluorescence-activated cell sorting (FACS) analysis of cell surface
      molecule expression. However, the lack of specific markers renders the
      characterization of MSCs difficult and sometimes ambiguous. MSCs posses
      remarkable expansion potential in culture and are highly amenable to genetic
      modification with various viral vectors rendering them optimal vehicles for cell
      based gene therapy. Most importantly, MSC plasticity and the possibility to use
      them as autologous cells render MSCs suitable for cell therapy and tissue
      engineering. Furthermore, it is known that MSCs produce and secrete a great
      variety of cytokines and chemokines that play beneficial paracrine actions when
      MSCs are used for tissue repair. In this chapter, we describe methods for
      isolation, ex vivo expansion, phenotypic characterization, and viral infection of
      MSCs from mouse bone marrow. We also describe a method for preparation of
      conditioned and concentrated conditioned medium from MSCs. The conditioned medium
      can be easily tested both in vitro and in vivo when a particular paracrine effect
      (i.e., cytoprotection) is hypothesized to be an important mechanism of action of
      the MSCs and/or screened to identify a target paracrine/autocrine mediator.

PMID- 19089364
TI  - Template DNA-strand co-segregation and asymmetric cell division in skeletal
      muscle stem cells.
AB  - Stem cells are present in all tissues and organs, and are crucial for normal
      regulated growth. How the pool size of stem cells and their progeny is regulated
      to establish the tissue prenatally, then maintain it throughout life, is a key
      question in biology and medicine. The ability to precisely locate stem and
      progenitors requires defining lineage progression from stem to differentiated
      cells, assessing the mode of cell expansion and self-renewal and identifying
      markers to assess the different cell states within the lineage. We have shown
      that during lineage progression from a quiescent adult muscle satellite cell to a
      differentiated myofibre, both symmetric and asymmetric divisions take place.
      Furthermore, we provide evidence that a sub-population of label retaining
      satellite cells co-segregate template DNA strands to one daughter cell. These
      findings provide a means of identifying presumed stem and progenitor cells within
      the lineage. In addition, asymmetric segregation of template DNA and the
      cytoplasmic protein Numb provides a landmark to define cell behaviour as self
      renewal and differentiation decisions are being executed.

PMID- 19089365
TI  - Isolation and grafting of single muscle fibres.
AB  - Satellite cells are mononucleate muscle precursor cells resident beneath the
      basal lamina, which surrounds each skeletal muscle fibre. Normally quiescent in
      adult muscle, in response to muscle damage satellite cells are activated and
      proliferate to generate a pool of muscle precursor cells, which subsequently
      differentiate and fuse together to repair and replace terminally differentiated
      muscle fibre syncytia. Cells prepared by enzymatic digestion of whole muscle
      tissue are likely to contain myogenic cells derived both from the satellite cell
      niche and from other populations in the muscle interstitium and vasculature.
      Single muscle fibre preparations, in which satellite cells retain their normal
      anatomical position beneath the basal lamina, are free of interstitial and
      vascular tissue and can therefore be used to investigate satellite cell behaviour
      in the absence of other myogenic cell types. Here, we describe methods for the
      isolation of viable muscle fibres and for grafting of muscle fibres and their
      associated satellite cells into mouse muscles to assess the contribution of
      satellite cells to muscle regeneration.

PMID- 19089366
TI  - Differentiation and dynamic analysis of primitive vessels from embryonic stem
      cells.
AB  - Embryonic stem (ES) cells, which are derived from developing mouse blastocysts,
      have the ability to differentiate into various cell types in vitro. When placed
      in basal medium with added serum, mouse ES cells undergo a programmed
      differentiation favoring formation of cell types that are found in the embryonic
      yolk sac, including vascular endothelial cells. These in vitro differentiated
      endothelial cells form primitive blood vessels, analogous to the first vessels
      that form in the embryo and the yolk sac. This differentiation model is ideal for
      both genetic and pharmacological manipulation of early vascular development. We
      have made mouse ES cell lines that express endothelial-specific GFP or H2B-GFP
      and used these lines to study the processes of mammalian vessel development by
      real-time imaging. Here we describe protocols for making transgenic ES cells and
      imaging the processes of blood vessel development. We also provide methods for ES
      cell maintenance and differentiation, and methods for analysis of vascular marker
      expression.

PMID- 19089367
TI  - Derivation of contractile smooth muscle cells from embryonic stem cells.
AB  - Smooth muscle cells (SMCs) play a key role in vascular physiology and pathology.
      An appreciation of normal SMCs developmental mechanisms will likely lead to a
      better understanding of disease processes and potentially to novel treatment
      strategies. We present a method for generating relatively pure populations of
      SMCs from embryonic stem cells (ESC) which display appropriate excitation and
      contractile responses to vasoactive agonists. We also present protocols for
      assessment of SMCs purity and identity by immunofluorescence, quantitative RT
      PCR, and FACS. This ESC-based system has tremendous potential for studying
      developmental regulation of SMC lineage, as well as for possible SMC tissue
      engineering.

PMID- 19089368
TI  - Islet-derived progenitors as a source of in vitro islet regeneration.
AB  - Current therapies do not prevent the complications of diabetes. Furthermore,
      these therapies do not address the underlying pathology; the lack of functional
      beta-cell mass that occurs in both types 1 and 2 diabetes. While pancreas and
      islet transplantation do serve to increase beta-cell mass, a lack of donor organs
      limits the therapeutic potential of these treatments. As such, expansion of beta
      cell mass from endogenous sources, either in vivo or in vitro, represents an area
      of increasing interest. One potential source of islet progenitors is the islet
      proper, via the dedifferentiation, proliferation, and redifferentiation of
      facultative progenitors residing within the islet. We have developed a tissue
      culture platform whereby isolated adult human pancreatic islets form
      proliferative duct-like structures expressing ductal and progenitor markers.
      Short-term treatment with a peptide fragment of islet neogenesis-associated
      protein (INGAP) induces these structures to reform islet-like structures that
      resemble freshly isolated islets with respect to the frequency and distribution
      of the four endocrine cell types, islet gene expression and hormone production,
      insulin content, and glucose-responsive insulin secretion. As such, the
      plasticity of adult human islets has significant implications for islet
      regeneration.

PMID- 19089370
TI  - Reprogramming of liver to pancreas.
AB  - Islet grafts have demonstrated that patients with diabetes would benefit greatly
      by beta-cell therapy. However, the paucity of available islets for
      transplantation as well as the immunological barriers faced in allogeneic
      transplantation represent a tremendous barrier to regenerative approaches to the
      treatment of diabetes. Here, we present a strategy and protocols to
      transdifferentiate developmentally related hepatocytes into beta-cells by the
      ectopic expression of critical beta-cell transcription factors.

PMID- 19089369
TI  - Isolation and characterization of hepatic stem cells, or "oval cells," from rat
      livers.
AB  - The pace of research on the potential therapeutic uses of liver stem cells or
      "oval cells" has accelerated significantly in recent years. Concurrent
      advancements in techniques for the isolation and characterization of these cells
      have helped fuel this research. Several models now exist for the induction of
      oval cell proliferation in rodents. Protocols for the isolation and culture of
      these cells have evolved to the point that they may be set up in any laboratory
      equipped for cell culture. The advent of magnetic cell sorting has eliminated
      reliance on expensive flow cytometric sorting equipment to generate highly
      enriched populations of oval cells. Our laboratory has had much success in using
      the oval cell surface marker Thy-1 in combination with magnetic sorting to
      produce material suitable for testing the influence of a myriad of chemical
      signaling molecules on the oval cell phenotype. This chapter will describe our
      basic strategy for oval cell induction and isolation. Additionally, two in vitro
      procedures are described which the reader may find useful in the early stages of
      developing an oval cell research project.

PMID- 19089371
TI  - Introduction: bacterial pathogens.

PMID- 19089372
TI  - Transcriptome analyses in the interaction of Neisseria meningitidis with
      mammalian host cells.
AB  - As in many other areas of basic and applied biology, research in infectious
      diseases has been revolutionized by two recent developments in the field of
      genome biology: first, the sequencing of the human genome as well as that of many
      pathogen genomes; and second, the development of high-throughput technologies
      such as microarray technology, proteomics, and metabolomics. Microarray studies
      enable a deeper understanding of genetic evolution of pathogens and investigation
      of determinants of pathogenicity on a whole-genome scale. Host studies in turn
      permit an unprecedented holistic appreciation of the complexities of the host
      cell responses at the molecular level. In combination, host-pathogen studies
      allow global analysis of gene expression in the infecting bacterium as well as in
      the infected host cell during pathogenesis providing a comprehensive picture of
      the intricacies of pathogen-host interactions. This chapter briefly explains the
      principles underlying DNA microarrays including major points to consider when
      planning and analyzing microarray experiments and highlights in detail their
      practical application using the interaction of Neisseria meningitidis with
      endothelial cells as an example.

PMID- 19089373
TI  - Surface-exposed adherence molecules of Streptococcus pneumoniae.
AB  - Surface-exposed proteins of pathogenic bacteria are considered as potential
      virulence factors through their direct contribution to host-pathogen
      interactions. The specific interaction of bacterial proteins with host proteins
      often subverts the physiologic function of host-derived proteins, and therefore
      the bacterial proteins are considered as key players in the infectious process.
      The direct binding of host proteins is exploited by the pathogens for
      colonization, host tissue invasion, or immune evasion. Strikingly, surface
      proteins such as ABC transporters are also implicated in bacterial pathogenesis
      through their role in maintenance of bacterial fitness. Here, we are interested
      in surface-exposed proteins of Streptococcus pneumoniae, which interact with host
      proteins including proteins of the extracellular matrix, serum proteins, or
      ectodomains of cellular host receptors. These bacterial proteins are termed
      collectively adhesins or MSCRAMMs (microbial surface components recognizing
      adhesive matrix molecules). We have shown that choline-binding proteins and
      proteins that lack classic features of surface proteins such as a signal peptide
      that is required for protein secretion or a membrane anchor motif represent a
      major class of adhesins produced by S. pneumoniae.

PMID- 19089374
TI  - Screening of virulence traits in Legionella pneumophila and analysis of the host
      susceptibility to infection by using the Dictyostelium host model system.
AB  - The social soil amoeba Dictyostelium discoideum has been established as a host
      model for several human pathogens including Legionella pneumophila. The complete
      genome sequence, the genetic tractability, and the phagocytic characteristics of
      Dictyostelium generate many opportunities for the study of host-pathogen
      interactions. Important applications of this haploid model organism are (i) the
      use of Dictyostelium cells as a screening system for bacterial virulence, (ii)
      the use of Dictyostelium mutant cells to identify genetic host determinants of
      susceptibility and resistance to infection, and (iii) experiments that allow the
      dissection of the complex cross-talk with infectious agents. Accordingly, this
      chapter describes a plaque assay to identify attenuated pathogens, an infection
      assay for the analysis of host cell mutants and pathogens, and a screening method
      for the isolation of Legionella mutants that are defective in the reprogramming
      of the phagolysosomal maturation of the host.

PMID- 19089375
TI  - Characterizing host receptor recognition by individual bacterial pathogens.
AB  - A critical determinant of host range and specificity relies on the ability of
      pathogenic bacteria to recognize eukaryotic cell surface molecules via
      specialized adhesins. The specific adhesin-receptor interaction allows pathogens
      to tightly bind to their target cells, thereby facilitating the colonization of
      host tissues. Therefore, the identification and characterization of bacterial
      adhesins is a major topic in infection biology. This chapter focuses on a rapid
      and simple method for the analysis of adhesin-receptor interactions that permits
      the characterization of receptor binding properties at the level of single
      bacteria. Accordingly, this methodological approach is ideally suited for the
      analysis of adhesins expressed in a phase-variable manner and for the study of
      heterogeneous bacterial populations. Besides focusing on the receptor-binding
      assay, this chapter describes the production of fluorescence-tagged soluble host
      receptor domains required for conducting this assay.

PMID- 19089376
TI  - Introduction: fungal pathogens.

PMID- 19089378
TI  - A method for examining glycans surface expression of yeasts by flow cytometry.
AB  - Recognition of pathogenic yeasts by host cells is based on components of the
      yeast cell wall, which are considered part of its virulence attributes. Cell wall
      glycans play an important role in the continuous interchange that regulates the
      balance between saprophytism and parasitism and between resistance and infection.
      Flow cytometry is a useful method for probing surface yeast glycans in order to
      compare their expression depending on strains and growth conditions. By using
      different monoclonal or polyclonal antibodies, levels of beta- and alpha-linked
      mannosides as well as beta-glucans can be successfully evaluated by flow
      cytometry methods. The cytometric method we describe here represents a useful
      tool to investigate to what extent yeasts are able to regulate their glycan
      surface expression and therefore modify their virulence properties.

PMID- 19089377
TI  - Isolation and purification of antigenic components of Cryptococcus.
AB  - The encapsulated fungal pathogens Cryptococcus neoformans and Cryptococcus gattii
      are significant agents of life-threatening infections, particularly in persons
      with suppressed cell-mediated immunity. This chapter provides detailed
      methodology for the purification of two of the major antigen fractions of C.
      neoformans: glucuronoxylomannan (GXM) and mannoprotein (MP). GXM is the primary
      component of the polysaccharide capsule, which is the major cryptococcal
      virulence factor. In contrast, MPs have been identified as key antigens that
      stimulate T-cell responses. Purification of GXM and MP should assist
      investigators studying the antigenic, biochemical, and virulence properties of
      Cryptococcus species.

PMID- 19089379
TI  - Human epithelial model systems for the study of Candida infections in vitro: part
      I. Adhesion to epithelial models.
AB  - Adhesion to host tissue represents one of the first steps during the early phase
      of fungal infections. In order to mediate pathogenesis in the infected host, this
      process is crucial for colonization and subsequent penetration of the respective
      tissue. In vivo analyses of the adhesion process in whole organisms are limited
      because of difficulties in providing reproducible and comparable conditions in
      the host environment. Therefore, in vitro assays provide the opportunity to study
      such processes under more defined conditions thus allowing for the analysis of
      events that are involved in more detail. Here we describe an in vitro adhesion
      assay making use of human epithelial cell lines to study fungal associations with
      host epithelia. This assay not only is suited to determine the rate of adhesion
      in a time-dependent manner but also facilitates global transcriptional profiling
      in order to determine the fungal response during adhesion at the molecular level.

PMID- 19089380
TI  - Human epithelial model systems for the study of Candida infections in vitro: part
      II. Histologic methods for studying fungal invasion.
AB  - Although the role of invasion in the virulence of Candida albicans has been
      demonstrated, the mechanism that governs fungal invasion is not fully understood.
      Among the tools that exist to fill these gaps in knowledge, in vitro tissue
      models based on reconstituted human epithelia (RHE) have already been developed.
      Such models are designed to study more reproducably the fungus-host relationship,
      as they eliminate the complexity and variability found in vivo. Herein we
      describe the preparation of these RHE and their application in study of the
      invasion properties of C. albicans by further histologic processing and
      microscopic observation. For this purpose, different epithelial cell lines are
      grown on a collagen gel to build up models of intestinal (Caco-2 cell line),
      vaginal (A431 cell line), and oral (TR146 cell line) mucosa. The use of these in
      vitro models applied to test the invasiveness of C. albicans strains (clinical
      isolates or gene deleted mutants) and to identify changes in gene expression
      during the invasion of the RHE will help to advance our knowledge of pathogenesis
      and to study specific mechanisms used by C. albicans to adapt to changing
      environments present in different epithelia. Furthermore, because these models
      are useful to study the host response during the challenge with the pathogen,
      they will also offer important new insights into host cell biology and identify
      new targets for treatment.

PMID- 19089381
TI  - In vitro systems for studying the interaction of fungal pathogens with primary
      cells from the mammalian innate immune system.
AB  - The incidence of invasive fungal diseases has increased over the past decades,
      particularly in relation with the increase of immunocompromised patient cohorts
      (e.g., HIV-infected patients, transplant recipients, immunosuppressed patients
      with cancer). Opportunistic fungal pathogens such as Candida spp. are most often
      associated with serious systemic infections. Currently available antifungal drugs
      are rather unspecific, often with severe side effects. In some cases, their
      prophylactic use has favored emergence of resistant fungal strains. Major
      antifungal drugs target the biosynthesis of lipid components of the fungal plasma
      membrane or the assembly of the cell wall. For a more specific and efficient
      treatment and prevention of fungal infection, new therapeutic strategies are
      needed, including strengthening or stimulation of the residual host immune
      response. Achieving such a goal requires a better understanding of factors
      important for the defense and the survival of the host combating Candida spp.
      Where possible, primary cultures of mammalian immune cells of the innate immune
      system constitute a better suited model than transformed cell lines to study host
      pathogen response and virulence. Hence, in vitro primary cell culture systems are
      a good strategy for a first screening of mutant strains of Candida spp. to
      identify virulence traits with regard to host cell response and pathogen
      invasion.

PMID- 19089382
TI  - Experimental infection of rodent mammals for fungal virulence testing.
AB  - Invasive fungal infections comprise a group of serious and life-threatening
      diseases affecting immunocompromised patients. Molecular analysis of fungal
      virulence involves the deletion of genes that are suspected for contributing to
      fungal pathogenesis. Phenotypic analysis of the generated mutants includes in
      vivo infection experiments in order to assign a function during fungal disease to
      a gene of interest.

PMID- 19089383
TI  - Real-time and semiquantitative RT-PCR methods to analyze gene expression patterns
      during Aspergillus-host interactions.
AB  - Aspergillus species are infamous for causing several plant and animal diseases
      that directly (e.g., invasive aspergillosis) or indirectly (e.g., consumption of
      toxic food supplies) can lead to high rates of morbidity in humans and animals
      worldwide. Despite progress in molecular information and manipulation of
      Aspergillus spp., including genome sequence availability and suitable
      transformation methodologies, efforts to control Aspergillus diseases are still
      far from satisfactory, due in part to lack of knowledge of fungal virulence
      attributes. In order to obtain meaningful insights on the disease mechanism(s),
      it is essential to detect virulence gene expression during host invasion. Here,
      we describe two PCR-based detection methods of Aspergillus gene expression in
      both plant and mammalian tissues. Moreover, these techniques can be employed for
      routine screening of large numbers of aspergilli to improve diagnosis, disease
      monitoring, and therapy of fungal disease.

PMID- 19089384
TI  - Antibody-based strategy to identify Candida albicans genes expressed during
      infections.
AB  - Investigators have long used antibody-based screening strategies to identify
      Candida albicans immunogenic proteins and the genes that encode them during
      infections. With the recent availability of the C. albicans genome sequence and
      the development of genomic and proteomic technologies, it is now possible to
      efficiently conduct large-scale screening in standard research labs. C. albicans
      proteins and genes identified with a variety of screening methods have been
      implicated as important determinants of candidal virulence and exploited as
      vaccine and therapeutic targets. In this chapter, we describe methods used in our
      lab, in which sera recovered from patients with candidiasis are used to screen a
      C. albicans genomic DNA expression library. Immunoreactive colonies are detected
      by reaction with anti-human immunoglobulin, and the corresponding open reading
      frames are identified using the genome sequence database. The methods are also
      suitable for use with cDNA expression libraries, and they are complementary to
      proteomic screening strategies described elsewhere in this volume.

PMID- 19089385
TI  - Identification of the Candida albicans immunome during systemic infection by mass
      spectrometry.
AB  - Over the past two decades, mass spectrometry (MS) has ceased to be a fairly
      exotic technique banished from the protein scientists' mind to become a seminal
      tool for deciphering the information encoded in the genomes of many biological
      species. Clues to this shift in the modus operandi for characterizing their
      proteomes stem from the progressive availability of full genome sequences and
      well-annotated protein databases of many model (micro)organisms, the development
      both of soft ionization methods for large biomolecules (peptides and proteins)
      and of innovative instrumentation designs, and the introduction of sophisticated
      search algorithms able to correlate MS information with sequence databases, to
      name but a few. Here we integrate the typical MS-based strategy for identifying
      proteins of Candida albicans, an opportunistic fungal pathogen of humans, which
      have proved to be present during systemic infection and targeted by the immune
      system as a consequence of its interaction with the host (i.e., the C. albicans
      immunome).

PMID- 19089386
TI  - Introduction: parasites.

PMID- 19089387
TI  - Axenic in vitro cultivation of Echinococcus multilocularis metacestode vesicles
      and the generation of primary cell cultures.
AB  - Parasitic helminths are a major cause of disease worldwide, yet the molecular
      mechanisms of host-helminth interaction and parasite development are only
      rudimentarily studied. A main reasons for this lack of knowledge are the
      tremendous experimental difficulties in cultivating parasitic helminths under
      defined laboratory conditions and obtaining sufficient amounts of parasite
      material for molecular analyses. For one member of this neglected group of
      pathogens, the fox-tapeworm Echinococcus multilocularis, we have established and
      optimized in vitro cultivation systems by which the major part of the parasite's
      life cycle, leading from early metacestode vesicles to the production of
      protoscoleces, can be mimicked under laboratory conditions. The methodology
      comprises co-cultivation systems for host cells and parasite larvae by which
      large amounts of parasite vesicles can be generated. Furthermore, we have
      established an axenic (host cell-free) cultivation system that allows studies on
      the influence of defined host factors on parasite growth and development. On the
      basis of this system, the isolation and maintenance of primary Echinococcus cells
      that are devoid of overgrowing host cells is now possible. The availability of
      the primary cell culture system constitutes a first step toward the establishment
      of genetic manipulation methods for the parasite that will be of great interest
      for further research on infection strategies and development of Echinococcus and
      other cestodes.

PMID- 19089388
TI  - Culture of exoerythrocytic stages of the malaria parasites Plasmodium falciparum
      and Plasmodium vivax.
AB  - The two most prevalent human malaria parasites, Plasmodium falciparum and
      Plasmodium vivax, cause the majority of malaria-related morbidity and mortality.
      Compared with our knowledge about the erythrocytic stages, we understand little
      about the liver exoerythrocytic (EE) stages of the human malaria parasites. Our
      recent development of a hepatocyte line from normal human liver tissue is crucial
      for successful culturing of the liver stages of both P. falciparum and P. vivax.
      This technical advancement should be an important tool for directly studying
      developmental biology of the EE stages of the human malaria parasites and
      developing drugs against parasite liver stages.

PMID- 19089389
TI  - Modulation of caspase activation by Toxoplasma gondii.
AB  - Apoptosis plays crucial roles for the outcome of infection with various
      infectious agents. The host's apoptotic program may be modulated after infection
      in order to combat the pathogen or to restrict the immune response. In addition,
      distinct microorganisms alter the apoptotic program of the host in order to meet
      the requirements for their further distribution. The activation of caspases
      (i.e., cysteine proteases with specificity for aspartic acid residues) preludes
      the disassembly of the cell in response to apoptosis-inducing stimuli. This
      depends on the proteolytic cleavage of inactive proforms into catalytically
      active subunits. Analyses of the proteolysis and the enzymatic activity of
      caspases therefore represent valuable tools to study apoptotic programs during
      infection. The apicomplexan parasite Toxoplasma gondii interferes with the
      caspase cascade of its host cell in order to facilitate intracellular survival.
      The modulation of caspase activation by T. gondii is determined by SDS-PAGE and
      immunoblotting with caspase-specific antibodies. Furthermore, the impact of the
      parasite on caspase activity is fluorimetrically determined by measuring the
      cleavage of caspase-specific substrate analogues.

PMID- 19089390
TI  - Introduction: host responses.

PMID- 19089391
TI  - Fungal and bacterial killing by neutrophils.
AB  - Neutrophils are professional phagocytes of the innate immune system that are
      essential to control bacterial and fungal infections. These cells engulf and kill
      invading microbes. Additionally, activated neutrophils are able to release
      neutrophil extracellular traps (NETs). These fibers consist of chromatin
      decorated with antimicrobial proteins to trap and kill microbes. Appropriate
      quantitative methods are required to understand the nature of interactions of
      neutrophils with pathogens. Here we present assays to measure killing mediated by
      phagocytosis, by NETs, by a combination of both, and by granular extract. As
      examples, we use Candida albicans for fungal and Shigella flexneri for bacterial
      pathogens.

PMID- 19089392
TI  - Endothelial cell stimulation by Candida albicans.
AB  - The opportunistic fungal pathogen Candida albicans enters the bloodstream and
      causes hematogenously disseminated infection in hospitalized patients. During the
      initiation of a hematogenously disseminated infection, endothelial cells are one
      of the first host cells to come in contact with C. albicans. Endothelial cells
      can significantly influence the local host response to C. albicans by expressing
      leukocyte adhesion molecules and proinflammatory cytokines. Thus, it is of
      interest to investigate the response of endothelial cells to C. albicans in
      vitro. We describe the use of real-time PCR and enzyme immunoassays to measure
      the effects of C. albicans on the endothelial cell production of E-selectin and
      tumor necrosis factor alpha in vitro.

PMID- 19089393
TI  - Models of oral and vaginal candidiasis based on in vitro reconstituted human
      epithelia for the study of host-pathogen interactions.
AB  - This protocol describes the setup, maintenance, and characteristics of models of
      oral and vaginal candidiasis based on well-established three-dimensional
      organotypic tissues of human oral and vaginal mucosa. Infection experiments are
      highly reproducible and can be used for the direct analysis of
      pathogen/epithelial cell interactions. Using the models, the several stages of
      infection by wild-type Candida albicans strains, the consequence of gene
      disruption of putative virulence factors in mutant cells, and the evaluation of
      the host immune response can be evaluated by histologic, biochemical, and
      molecular methods. As such, the models provide clear answers regarding protein
      and gene expression that are not complicated by nonepithelial factors. To study
      the impact of several host components, the mucosal infection models can be
      supplemented with immune cells, saliva, and probiotic bacteria, which might be
      relevant for host defense. It requires at least 3 days to be established and can
      be maintained thereafter for 2 to 4 days.

PMID- 19089394
TI  - Phagocytosis of Candida albicans by RNAi-treated Drosophila S2 cells.
AB  - Phagocytosis is a highly conserved aspect of innate immunity. Drosophila
      melanogaster has an innate immune system with many similarities to that of
      mammals and has been used to successfully model many aspects of innate immunity.
      The recent availability of Ribo Nucleic Acid interference (RNAi) libraries for
      Drosophila has made it possible to efficiently screen for genes important in
      aspects of innate immunity. We have screened an RNAi library representing 7216
      fly genes conserved among metazoans to identify proteins required for the
      phagocytosis of the human fungal pathogen Candida albicans.

PMID- 19089395
TI  - Oral mucosal cell response to Candida albicans in transgenic mice expressing HIV
      1.
AB  - Controlled studies on the immunopathogenesis of mucosal candidiasis in HIV
      infection have been hampered by the lack of a relevant animal model. We have
      previously reported that oral Candida infection in CD4C/HIV transgenic mice
      expressing gene products of HIV-1 in immune cells and developing an AIDS-like
      disease closely mimics oropharyngeal candidiasis in human HIV infection. The role
      of defective dendritic cells and CD4+ T cells in impaired induction of protective
      immunity and in the phenotype of chronic oral carriage of C. albicans can now be
      investigated under controlled conditions in these transgenic mice.

PMID- 19089396
TI  - Proteomic profiling of serologic response to Candida albicans during host
      commensal and host-pathogen interactions.
AB  - Candida albicans is a commensal inhabitant of the normal human microflora that
      can become pathogenic and invade almost all body sites and organs in response to
      both host-mediated and fungus-mediated mechanisms. Serologic responses to C.
      albicans that underlie its dichotomist relationship with the host (host-commensal
      and host-pathogen interactions) display a high degree of heterogeneity, resulting
      in distinct serum anti-Candida antibody signatures (molecular fingerprints of
      anti-Candida antibodies in serum) that can be used to discriminate commensal
      colonization from invasive disease. We describe the typical proteomic strategy to
      globally and integratively profile these host antibody responses and determine
      serum antibody signatures. This approach is based on the combination of classic
      immunoproteomics or serologic proteome analysis (two-dimensional electrophoresis
      followed by quantitative Western blotting and mass spectrometry) with data mining
      procedures. This global proteomic stratagem is a useful tool not only for
      obtaining an overview of different anti-Candida antibodies that are being
      elicited during the host-fungus interaction and, consequently, of the complex C.
      albicans immunome (the subset of the C. albicans proteome targeted by the immune
      system), but also for evaluating how this pathogen organism interacts with its
      host to trigger infection. In contrast with genomics and transcriptomics, this
      proteomic technology has the potential to detect antigenicity associated with
      posttranslational modification, subcellular localization, and other functional
      aspects that can be relevant in the host immune response. Furthermore, this
      strategy to define molecular fingerprints of serum anti-Candida antibodies may
      hopefully bring to light potential candidates for diagnosis, prognosis, risk
      stratification, clinical follow-up, therapeutic monitoring, and/or immunotherapy
      of candidiasis, especially of its life-threatening systemic forms.

PMID- 19089397
TI  - Toll-like receptors, wound healing, and carcinogenesis.
AB  - Following acute injury, the concerted action of resident and nonresident cell
      populations evokes wound healing responses that entail a temporary increase in
      inflammation, extracellular matrix production, and proliferation to ultimately
      restore normal organ architecture. However, chronic injury evokes a perpetuating
      wound healing response promoting the development of fibrosis, organ failure, and
      cancer. Recent evidence points toward toll-like receptors (TLRs) as important
      regulators of inflammatory signals in wound healing. Here, we will review the
      activation of TLRs by different endogenous and bacterial TLR ligands during wound
      healing, and the contribution of TLR-induced signals to injury, fibrogenesis,
      regeneration, and carcinogenesis. We will discuss the hypothesis that TLRs act as
      sensors of danger signals in injured tissue to switch the wound healing response
      toward fibrogenesis and regeneration as a protective response to imminent danger
      at the cost of an increased long-term risk of developing scars and cancer.

PMID- 19089398
TI  - The last polar dinosaurs: high diversity of latest Cretaceous arctic dinosaurs in
      Russia.
AB  - A latest Cretaceous (68 to 65 million years ago) vertebrate microfossil
      assemblage discovered at Kakanaut in northeastern Russia reveals that dinosaurs
      were still highly diversified in Arctic regions just before the Cretaceous
      Tertiary mass extinction event. Dinosaur eggshell fragments, belonging to
      hadrosaurids and non-avian theropods, indicate that at least several latest
      Cretaceous dinosaur taxa could reproduce in polar region and were probably year
      round residents of high latitudes. Palaeobotanical data suggest that these polar
      dinosaurs lived in a temperate climate (mean annual temperature about 10 degrees
      C), but the climate was apparently too cold for amphibians and ectothermic
      reptiles. The high diversity of Late Maastrichtian dinosaurs in high latitudes,
      where ectotherms are absent, strongly questions hypotheses according to which
      dinosaur extinction was a result of temperature decline, caused or not by the
      Chicxulub impact.

PMID- 19089399
TI  - Frequent summer nuptial flights of ants provide a primary food source for bats.
AB  - In many ant species, nuptial flight tends to be short in time and assumed to be
      synchronous across a large area. Here, we report that, in the upper Jordan
      Valley, northern Israel, massive nuptial flights of Carpenter ants (Camponotus
      sp.) occur frequently throughout the summer, and their alates form up to 90% of
      the diet of the greater mouse-tailed bat (Rhinopoma microphyllum) during this
      period. This fat and protein-rich diet enables female bats to lactate during
      summer, and the large amount of fat that both sexes accumulate may serve as an
      energy source for their following winter hibernation and posthibernation mating
      in early spring (March-April). We suggest that the annual movement of these bats
      to the Mediterranean region of Israel may have evolved in order to enable them to
      exploit the extremely nutritious forms of ant alates when the bats' energetic
      demands are highest.

PMID- 19089400
TI  - Reproductive disturbance of Japanese bumblebees by the introduced European
      bumblebee Bombus terrestris.
AB  - The European bumblebee, Bombus terrestris, is an invasive eusocial species whose
      distribution is expanding greatly beyond its native range because numerous
      colonies are imported to or locally produced in non-native countries for
      pollination of agricultural crops. Closely related species exist in Japan where
      the unrestricted import and use of B. terrestris has resulted in the
      establishment of wild colonies. Laboratory studies previously showed that B.
      terrestris and Japanese native species can copulate and produce fertilized eggs.
      Although these eggs do not hatch, the interspecific mating can cause a serious
      reproductive disturbance to native bumblebees. In this study, we determined the
      frequencies of interspecies mating between B. terrestris males and native
      bumblebee queens in the wild on the islands of Hokkaido and Honshu by analyzing
      the DNA sequences of spermatozoa stored in spermathecae of native queens. We
      found that 20.2% of B. hypocrita hypocrita queens and 30.2% of B. hypocrita
      sapporoensis queens had spermatozoa of B. terrestris males in their spermathecae.
      Given that a Bombus queen generally mates only once in her life, such high
      frequencies of interspecific mating with B. terrestris pose serious threats to
      the populations of native bumblebees in Japan.

PMID- 19089401
TI  - Discrimination of flicker frequency rates in the reptile tuatara (Sphenodon ).
AB  - By investigating the mechanisms that underlie the perception of environmental
      cues, we may begin to understand how the sensory system governs behavioral
      responses. This is the first empirical study to examine learning and visual
      sensitivity in a reptile species, the tuatara (Sphenodon punctatus). We
      established a non-intrusive psychophysical method by employing an instrumental
      paradigm in order to examine discrimination learning and the ability to
      distinguish different flicker frequencies in the tuatara. Seventeen tuatara were
      trained under an operant conditioning task to respond to various discriminative
      stimuli flickering between 2.65 and 65.09 Hz. Tuatara were able to learn the
      operant task and discriminate between a constant light and flicker frequency
      rates between 2.65 and 45.61 Hz, but not at 65.09 Hz. We demonstrated a reliable
      psychophysical method where these reptiles could learn a basic operant task and
      discriminate visual stimuli in the form of flicker frequency rates. The tuatara's
      ability to perceive flickering light is comparable to that of avian, mammalian,
      and other reptilian species. This method is thus suitable for more comprehensive
      examinations of vision and additional sensory abilities in other reptiles.

PMID- 19089402
TI  - [Role of lymph node dissection in prostate cancer].
AB  - We present a comprehensive literature review and critical discussion of the
      diagnostic and therapeutic value of lymph node dissection in prostate cancer.
      Lymph node dissection is currently the most reliable staging procedure for
      detecting lymph node metastases in prostate cancer. Accuracy increases with the
      extent of the procedure. Overall, in patients with positive lymph nodes after
      radical prostatectomy and lymph node dissection, a favorable long-time cancer
      specific survival can be observed. These data seem to be independent of the
      extent of the lymph node dissection and also independent of the administration of
      adjuvant therapy. It can be suspected that patients with lymph node metastases
      present different prognostic groups based on the extent of lymph node
      involvement. However, these risk groups might reflect only a lead-time bias, so
      the therapeutic value of lymph node dissection remains unclear. In conclusion,
      the therapeutic value of lymph node dissection in prostate cancer must be
      sufficiently evaluated in prospective clinical trials. Each patient should be
      individually counseled regarding his individual tumor features and the use of
      statistical prognostic tools such as nomograms.

PMID- 19089403
TI  - Cannabinoid type 1 receptors in human skeletal muscle cells participate in the
      negative crosstalk between fat and muscle.
AB  - AIMS/HYPOTHESIS: Cannabinoid type 1 receptor (CB1R) antagonists such as
      rimonabant (Rim) represent a novel approach to treat obesity and related
      metabolic disorders. Recent data suggest that endocannabinoids are also produced
      by human adipocytes. Here we studied the potential involvement of
      endocannabinoids in the negative crosstalk between fat and muscle. METHODS: The
      protein level of CB1R in human skeletal muscle cells (SkM) during differentiation
      was analysed using western blotting. SkM were treated with adipocyte-conditioned
      medium (CM) or anandamide (AEA) in combination with the CB1R antagonists Rim or
      AM251, and insulin-stimulated Akt phosphorylation and glucose uptake were
      determined. Furthermore, signalling pathways of CB1R were investigated. RESULTS:
      We revealed an increase of CB1R protein in SkM during differentiation. Twenty
      four hour incubation of SkM with CM or AEA impaired insulin-stimulated
      Akt(Ser473) phosphorylation by 60% and up to 40%, respectively. Pretreatment of
      cells with Rim or AM251 reduced the effect of CM by about one-half, while the
      effect of AEA could be prevented completely. The reduction of insulin-stimulated
      glucose uptake by CM was completely prevented by Rim. Short-time incubation with
      AEA activated extracellular regulated kinase 1/2 and p38 mitogen-activated
      protein kinase, and impaired insulin-stimulated Akt(Ser473) phosphorylation, but
      had no effect on Akt(Thr308) and glycogen synthase kinase 3alpha/beta
      phosphorylation. In addition, enhanced IRS-1 (Ser307) phosphorylation was
      observed. CONCLUSIONS/INTERPRETATION: Our results show that the CB1R system may
      play a role in the development of insulin resistance in human SkM. The results
      obtained with CM support the notion that adipocytes may secrete factors which are
      able to activate the CB1R. Furthermore, we identified two stress kinases in the
      signalling pathway of AEA and enhanced IRS-1(Ser307) phosphorylation, potentially
      underlying the development of insulin resistance.

PMID- 19089405
TI  - [Immobilization by external rotation after primary traumatic shoulder
      dislocation].
AB  - Immobilization of the shoulder following dislocation and reduction is
      traditionally carried out using internal rotation braces. However, high
      recurrence rates of up to 96% may result depending on several concomitant
      intrinsic and extrinsic prognostic factors, such as age and level of physical
      activity. Recently, different cadaveric and radiologic studies have suggested an
      improved tissue apposition of the affected labroligamentous structures in a
      better anatomic position during external rotation of the humeral head. Recent
      clinical outcome studies have supported the hypothetical benefit of this
      immobilization technique. Significantly lower recurrent dislocation rates and a
      better anatomic positioning of the affected structures were observed after
      immobilization in external rotation compared to immobilization in internal
      rotation.However, the number of available studies in this respect is still
      limited. Further prospective evidence is therefore desirable to evaluate the
      contribution of exact positioning of the immobilization, influence of hemarthros
      and specific capsulolabral lesions to the long-term clinical and radiological
      outcome of this new concept of immobilization.

PMID- 19089406
TI  - [Rehabilitation following total hip and knee replacement].
AB  - For the more than 330.000 patients/year with primary total hip replacement (THR)
      or total knee replacement (TKR) in Germany alone, postoperative rehabilitation
      either on an inpatient or follow-up outpatient basis is largely accepted as
      standard, despite limited financial resources. The present article discusses the
      necessary diagnostic and therapeutic measures in the immediate postoperative
      phase in the hospital or clinic, the so-called post-inpatient phase in a
      rehabilitation clinic or centre, as well as the subsequent outpatient phase with
      consistent and regular specialist follow-up.

PMID- 19089407
TI  - Arthroscopic excision of sternoclavicular joint.
AB  - We report an unusual case of chronic inflammatory arthropathy involving the
      sternoclavicular joint. Arthroscopic debridement of the sternoclavicular joint
      cavity was accompanied with the arthroscopic excision of the medial end of
      clavicle. Twelve months post-surgery the patient is asymptomatic with no signs of
      recurrence and a full pain free range of movement.

PMID- 19089408
TI  - Intercondylar roof impingement pressure after anterior cruciate ligament
      reconstruction in a porcine model.
AB  - Anterior cruciate ligament (ACL) graft impingement against the intercondylar roof
      has been postulated, but not thoroughly investigated. The roof impingement
      pressure changes with different tibial and femoral tunnel positions in ACL
      reconstruction. Anterior tibial translation is also affected by the tunnel
      positions of ACL reconstruction. The study design included a controlled
      laboratory study. In 15 pig knees, the impingement pressure between ACL and
      intercondylar roof was measured using pressure sensitive film before and after
      ACL single bundle reconstruction. ACL reconstructions were performed in each knee
      with two different tibial and femoral tunnel position combinations: (1) tibial
      antero-medial (AM) tunnel to femoral AM tunnel (AM to AM) and (2) tibial postero
      lateral (PL) tunnel to femoral High-AM tunnel (PL to High-AM). Anterior tibial
      translation (ATT) was evaluated after each ACL reconstruction using
      robotic/universal force-moment sensor testing system. Neither the AM to AM nor
      the PL to High-AM ACL reconstruction groups showed significant difference when
      compared with intact ACL in roof impingement pressure. The AM to AM group had a
      significantly higher failure load than PL to High-AM group. This study showed how
      different tunnel placements affect the ACL-roof impingement pressure and anterior
      posterior laxity in ACL reconstruction. Anatomical ACL reconstruction does not
      cause roof impingement and it has a biomechanical advantage in ATT when compared
      with non-anatomical ACL reconstructions in the pig knee. There is no
      intercondylar roof impingement after anatomical single bundle ACL reconstruction.

PMID- 19089409
TI  - Mucoid degeneration of the anterior cruciate ligament.
AB  - Mucoid degeneration of the anterior cruciate ligament (ACL) is a rare cause of
      knee pain. We report a case of a patient with mucoid degeneration of the ACL,
      presenting with posterior knee pain and no history of a major knee trauma. On
      clinical examination, the active range of motion showed a flexion deficit. The
      posterior knee pain was induced by passive hyperflexion of the knee. There was no
      evidence of ligamentary instability. MRI showed a diffuse thickening of the ACL
      with a nodular mass on the femoral insertion occupying the intercondylar notch,
      with increased signal intensity on both T1- and T2-weighted images. Arthroscopic
      evaluation showed a diffuse hypertrophy of the ACL, throughout the entire length
      of the posterolateral bundle (PLB). A yellowish homogenous mass on the femoral
      insertion of the ACL impinged on the posterior cruciate ligament (PCL) in flexion
      and occupied the entire intercondylar notch. We performed an arthroscopic
      debridement of the hypertrophied tissues as precisely as possible. This resulted
      in a nearly complete removal of the PLB and immediate relief of symptoms.
      Examination of knee stability after debridement showed a stable ACL. Arthroscopic
      debridement of the mucoid degeneration of the ACL proved to be a safe and
      effective method, without causing ligamentary instability in daily activities.

PMID- 19089411
TI  - Effects of C-terminal amino acids truncation on enzyme properties of Aeromonas
      caviae D1 chitinase.
AB  - C-terminal truncation mutagenesis was used to explore the functional and
      structural significance of the C-terminal region of Aeromonas caviae D1 chitinase
      (AcD1ChiA). Comparative studies between the engineered full-length AcD1ChiA and
      the truncated mutant (AcD1ChiAK606) included initial rate kinetics, fluorescence
      and circular dichroism (CD) spectrometric properties, and substrate binding and
      hydrolysis abilities. The overall catalytic efficiency, k(cat)/K(M), of
      AcD1ChiAK606 with the 4MU-(GlcNAc)(2) and the 4MU-(GlcNAc)(3) chitin substrates
      was 15-26% decreased. When compared with AcD1ChiA, the truncated mutant
      AcD1ChiAK606 maintained 80% relative substrate-binding ability and about 76% of
      the hydrolyzing efficiency against the insoluble alpha-chitin substrate. Both
      fluorescence and CD spectroscopy indicated that AcD1ChiAK606 retained the same
      conformation as AcD1ChiA. These results indicated that removal of the C-terminal
      259 amino acid residues, including the putative chitin-binding motif and the A
      region (a motif of unknown function) of AcD1ChiA, did not seriously affect the
      enzyme structure integrity as well as activity. The present study provided
      evidences illustrating that the binding and hydrolyzing of insoluble chitin
      substrates by AcD1ChiA were not absolutely dependent on the putative C-terminal
      chitin-binding domain and the function-unknown A region.

PMID- 19089410
TI  - A soluble factor (EMMPRIN) in exudate influences knee motion after total
      arthroplasty.
AB  - Few studies have been conducted to investigate biological factors that affect
      postoperative knee motion after total knee arthroplasty (TKA). The purpose of
      this study is to test the hypothesis that range of knee motion (ROM) at 4 weeks
      after TKA is correlated with the concentration of extracellular matrix
      metalloproteinase inducer (EMMPRIN) and transforming growth factor (TGF)-beta1 in
      the exudative fluid harvested from the joint after surgery. A prospective
      measurement study was conducted with 20 osteoarthritis patients who underwent
      TKA. At 48 h after surgery, the exudate was harvested from a closed drainage
      system. Enzyme-linked immunosorbent assay was performed to measure the
      concentration of TGF-beta1, EMMPRIN, MMP-1, 2, 9, tissue inhibitor of
      metalloproteinase-1, and Hyalunonan. Knee flexion angle was measured before and
      at 4 weeks after surgery. There was a significant correlation between the EMMPRIN
      levels and knee flexion angle (r = 0.557, p = 0.0148). Western blot analysis of
      the exudate showed a prominent band for EMMPRIN at 27 kDa. On the other hand,
      there was no correlation between the TGF-beta1 levels and the knee flexion angle.
      This study showed that EMMPRIN levels after TKA affect the postoperative ROM. As
      to clinical relevance, EMMPRIN in the exudate after TKA is a promising biological
      indicator to predict difficulty in restoring postoperative ROM.

PMID- 19089412
TI  - Hormetic acute response and chronic effect of ethanol on adenine nucleotide
      hydrolysis in rat platelets.
AB  - The objective of this study was to verify the acute and chronic effects of
      ethanol on platelet NTPDase and 5'-nucleotidase activities. These enzymes
      modulate platelet function by regulating adenine nucleotide bioavailability and
      adenosine production. In the acute treatment, doses of 0.8, 2.0, 4.0, 6.0 and 8.0
      g/kg ethanol were administered via orogastric tube, and induced a biphasic or
      hormetic effect on ATP, ADP and AMP platelet hydrolysis. Ethanol at a dose of 0.8
      and 2.0 g/kg increased NTPDase activity (44 and 35%, P < 0.0001) with ATP as
      substrate, whereas when ADP was used there was only a tendency for NTPDase
      activity to increase. ATP and ADP hydrolysis decreased by 31-77% (P < 0.0001) in
      4.0, 6.0 and 8.0 g/kg of ethanol compared to the control. AMP hydrolysis showed a
      tendency to increase at ethanol doses of 0.8 and 2.0 g/kg, but was inhibited by
      45-100% (P < 0.0001) at the higher doses. Chronic treatment consisted of the oral
      administration of 20% ethanol solution during 31 weeks as the only source of
      liquid and inhibited NTPDase activity (15 and 20%, P < 0.05) with ATP and ADP as
      substrate, respectively. However, AMP hydrolysis by 5'-nucleotidase increased by
      40% (P < 0.05). Thus, we speculate that the effects of ethanol on NTPDase and 5'
      nucleotidase activities could be related with the platelets alterations commonly
      observed in alcohol users.

PMID- 19089413
TI  - Control of ionic transport through gated single conical nanopores.
AB  - Control of ionic transport through nanoporous systems is a topic of scientific
      interest for the ability to create new devices that are applicable for ions and
      molecules in water solutions. We show the preparation of an ionic transistor
      based on single conical nanopores in polymer films with an insulated gold thin
      film "gate." By changing the electric potential applied to the "gate," the
      current through the device can be changed from the rectifying behavior of a
      typical conical nanopore to the almost linear behavior seen in cylindrical
      nanopores. The mechanism for this change in transport behavior is thought to be
      the enhancement of concentration polarization induced by the gate.

PMID- 19089415
TI  - Particle stability in polymer-assisted reverse colorimetric DNA assays.
AB  - "Reverse" colorimetric DNA detection by the formation of core-shell particles
      upon DNA hybridization is described. Specifically, the assay is based on a
      strategy to covalently link polymer reaction initiators to suspended
      nanoparticles upon DNA hybridization. These initiators then prompt polymer chain
      growth to form a thick polymer shell outside of particles, acting as the physical
      barrier to keep Au particles apart. Particles without DNA hybridization
      aggregate, accompanied by a pronounced solution color change from red to blue.
      The focus of this report is to address reaction kinetics of two co-occurring
      processes: polymer growth and particle aggregation during the reverse
      colorimetric DNA assay. The results show that Cu ions used as the polymerization
      catalyst bind strongly to the bases in DNA molecules, resulting in crosslinking
      of DNA-attached gold nanoparticles and their subsequent precipitation. Both Cu
      ion-assisted particle aggregation and polymer growth are found to depend strongly
      on Cu ion concentration, salt concentration, and reaction temperature. Under the
      optimized conditions, faster polymer chain growth on the surface overcomes
      particle aggregation and preserves particle stability via steric stabilization.

PMID- 19089416
TI  - Interventional radiology for paediatric trauma.
AB  - Paediatric interventional radiology plays a cornerstone role in the management of
      paediatric trauma. In the acute setting, interventional radiology techniques
      allow minimally invasive control of haemorrhage or re-establishment of blood
      flow. Percutaneous stenting and drainage can allow disruptions in urinary or
      biliary systems to heal without the need for further surgery. Interventional
      radiology techniques also have a significant role in treating delayed
      complications of trauma, including embolization of arterial pseudoaneurysms and
      pulmonary embolism prophylaxis in individuals immobilized due to the trauma or
      its operative treatment.

PMID- 19089417
TI  - Xanthogranulomatous adrenalitis in a neonate: CT and US findings.
AB  - We report a 46-day-old female infant with xanthogranulomatous adrenalitis.
      Ultrasonography showed a complex, solid-cystic right suprarenal mass with poorly
      defined margins. Colour flow Doppler revealed the solid portion of the mass to be
      vascular. CT demonstrated a heterogeneous cystic and solid mass with some
      contrast enhancement in the inferior part of the lesion. There was compression of
      the adjacent upper pole of the right kidney and the lateral aspect of the
      inferior vena cava. The mass was completely removed; histological examination
      revealed xanthogranulomatous adrenalitis. At the time of this report she remained
      well 3 years following surgery.

PMID- 19089418
TI  - Autosomal recessive polycystic kidney disease and congenital hepatic fibrosis
      (ARPKD/CHF).
AB  - ARPKD/CHF is an inherited disease characterized by non-obstructive fusiform
      dilatation of the renal collecting ducts leading to enlarged spongiform kidneys
      and ductal plate malformation of the liver resulting in congenital hepatic
      fibrosis. ARPKD/CHF has a broad spectrum of clinical presentations involving the
      kidney and liver. Imaging plays an important role in the diagnosis and follow-up
      of ARPKD/CHF. Combined use of conventional and high-resolution US with MR
      cholangiography in ARPKD/CHF patients allows detailed definition of the extent of
      kidney and hepatobiliary manifestations without requiring ionizing radiation and
      contrast agents.

PMID- 19089420
TI  - (18)F-FDG PET analysis of schwannoma: increase of SUVmax in the delayed scan is
      correlated with elevated VEGF/VPF expression in the tumors.
AB  - OBJECTIVE: In order to clarify the increased 2-deoxy-2-fluoro-(18)F-D: 
      glucopyranose ((18)F-FDG) accumulation in schwannoma by positron emission
      tomography (PET) analysis, immunohistochemical analysis for the factors involved
      in glucose transportation and vascular formation was performed. MATERIALS AND
      METHODS: Twenty-six patients with schwannoma (13 men and 13 women) with ages
      ranging from 27 to 75 years, who received whole body (18)F-FDG PET scan, were
      enrolled for the present study. The retention index (RI) was calculated by
      dividing the increase in the standardized uptake value (SUVmax) at the delayed
      scan by the SUVmax in the early scan. SUVmax and RI were compared with the
      histologic variables, including the expression of glucose transporters 1 and 3,
      hexokinase II, vascular endothelial growth factor/vascular permeability factor
      (VEGF/VPF), and microvascular density shown by CD31 immunohistochemistry.
      RESULTS: Mean SUVmax values in the early and delayed scans were 2.64 +/- 1.47 and
      2.71 +/- 1.57 (mean +/- SD), respectively. RI was -2.5 +/- 21 (percentage).
      SUVmax showed a positive correlation with the tumor size (tumor size <5 cm, 2.06
      +/- 0.72; >5 cm, 3.95 +/- 1.89; p < 0.05) and the microvascular density (negative
      density, 2.16 +/- 1.12; positive density, 3.56 +/- 1.67; p < 0.05). RI correlated
      with VEGF/VPF expression in the tumors (negative expression, -11 +/- 6.1;
      positive expression, 13 +/- 8.1; p < 0.05). Other factors showed no correlation
      with SUVmax or RI. CONCLUSIONS: Microvascular density and vascular permeability
      of the tumor are suggested to affect the enhanced (18)F-FDG accumulation in
      schwannoma.

PMID- 19089419
TI  - Can T2 relaxation values and color maps be used to detect chondral damage
      utilizing subchondral bone marrow edema as a marker?
AB  - OBJECTIVE: This study aimed to investigate whether a commercially available time
      efficient T2 mapping sequence will demonstrate findings of articular cartilage
      degeneration based on T2 relaxation values (RV) and color maps, using subchondral
      bone marrow edema (BME) as a marker for chondral damage. MATERIALS AND METHODS:
      The patient group consisted of 88 subjects who underwent knee magnetic resonance
      imaging at 1.5 T who had subchondral BME evident on fat-suppressed T2-weighted
      sequences. The control group was comprised of 60 subjects with no evidence of
      subchondral BME. A commercially available eight echo T2 relaxation sequence
      (acquisition time 8:36 min) was used to construct a T2 color map and to determine
      T2 RVs. T2 RVs were determined on cartilage overlying subchondral BME in patients
      and in eight pre-determined anatomical regions in controls. T2 color maps in the
      patient and control groups were analyzed for degree of color stratification
      (presence = two or more colors) at the same anatomic site as that used for T2 RV
      determination. RESULTS: T2 RVs were significantly increased in patients compared
      to controls for the medial femoral condyle (MF; p < 0.01), medial patellar facet
      (MP; p < 0.01), lateral patellar facet (LP; p < 0.01), lateral femoral condyle
      (LF; p < 0.01) and lateral tibial plateau (LT; p < 0.01). Loss of color
      stratification was noted in patients compared to controls in the medial tibial
      plateau (MT; p = 0.01), LF (p < 0.01), and LT (p < 0.01). In the patient group,
      increase in T2 RVs was associated with corresponding decrease in color
      stratification in MF (p < 0.01), MT (p < 0.01), MP (p < 0.01), medial femoral
      trochlear groove (p = 0.02), and lateral femoral trochlear groove (p < 0.01).
      CONCLUSION: Subchondral BME was associated with an increase in adjacent articular
      cartilage T2 RVs at some sites. Also, elevated T2 RVs were associated with loss
      of color stratification.

PMID- 19089422
TI  - False-negative thyroglobulin measurement in recurrent/metastatic thyroid
      carcinomas.

PMID- 19089424
TI  - TNK cells (NKG2D+ CD8+ or CD4+ T lymphocytes) in the control of human tumors.
AB  - Innate and adaptive immune responses have many interactions that are regulated by
      the balance of signals initiated by a variety of activatory and inhibitory
      receptors. Among these, the NKG2D molecule was identified as expressed by T
      lymphocytes, including most CD8+ cells and a minority of CD4+ cells, designated
      TNK cells in this paper. Tumor cells may overexpress the stress-inducible NKG2D
      ligands (NKG2DLs: MICA/B, ULBPs) and the NKG2D signaling has been shown to be
      involved in lymphocyte-mediated anti-tumor activity. Aberrant expression of
      NKG2DLs by cancer cells, such as the release of soluble form of NKG2DLs, can lead
      to the impairment of these immune responses. Here, we discuss the significance of
      NKG2D in TNK-mediated anti-tumor activity. Our studies demonstrate that NKG2D+ T
      cells (TNK) are commonly recruited at the tumor site in melanoma patients where
      they may exert anti-tumor activity by engaging both TCR and NKG2D. Moreover,
      NKG2D and TCR triggering was also observed by peripheral blood derived T
      lymphocyte- or T cell clone-mediated tumor recognition, both in melanoma and
      colorectal cancer (CRC) patients. Notably, heterogeneous expression of NKG2DLs
      was found in melanoma and CRC cells, with a decrease of these molecules along
      with tumor progression. Therefore, through the mechanisms that govern NKG2D
      engagement in anti-tumor activity and the expression of NKG2DLs by tumor cells
      that still need to be dissected, we showed that NKG2D expressing TNK cells are a
      relevant T cell subtype for immunosurveillance of tumors and we propose that new
      immunotherapeutic interventions for cancer patients should be aimed also at
      enhancing NKG2DLs expression by tumor cells.

PMID- 19089425
TI  - Comparison of a new minimum contact locking plate and the limited contact dynamic
      compression plate in an osteoporotic fracture model.
AB  - The purpose of this study was to investigate the biomechanical properties of a
      new minimum contact locking plate (MC-LP) compared with the limited contact
      dynamic compression plate (LC-DCP). Eighteen pairs of fresh human osteoporotic
      cadaver radii were equally divided into three groups. Each specimen was tested in
      each of the following force applications: anteroposterior (AP) four point
      bending, mediolateral (ML) four point bending, and torsion. A 10-mm gap osteotomy
      model was used to simulate a comminuted diaphyseal radial fracture. For each
      pair, one radius received a limited contact dynamic compression plate (LC-DCP)
      and the contralateral radius was fixed with a minimum contact locking plate (MC
      LP). Specimens were tested in nondestructive four point bending and torsion on an
      electronic universal material testing system. The results indicate that the MC-LP
      system is significantly more stable than the LC-DCP system when tested in four
      point bending and torsion in an osteoporotic comminuted radial diaphyseal
      fracture model.

PMID- 19089423
TI  - A cell-based high-throughput screen to identify synergistic TRAIL sensitizers.
AB  - We have developed a high-throughput screen (HTS) to search for novel molecules
      that can synergize with TRAIL, thus promoting apoptosis of ACHN renal tumor cells
      in a combinatorial fashion. The HTS detects synthetic compounds and pure natural
      products that can pre-sensitize the cancer cells to TRAIL-mediated apoptosis, yet
      have limited toxicity on their own. We have taken into account the individual
      effects of the single agents, versus the combination, and have identified hits
      that are synergistic, synergistic-toxic, or additive when combined with TRAIL in
      promoting tumor cell death. Preliminary mechanistic studies indicate that a
      subset of the synergistic TRAIL sensitizers act very rapidly to promote cleavage
      and activation of caspase-8 following TRAIL binding. Caspase-8 is an apical
      enzyme that initiates programmed cell death via the extrinsic apoptotic pathway.
      Thus, these TRAIL sensitizers may potentially reduce resistance of tumor cells to
      TRAIL-mediated apoptosis. Two representative sensitizers were found to increase
      levels of p53 but did not inhibit the proteasome, suggesting that early DNA
      damage-sensing pathways may be involved in their mechanisms of action.

PMID- 19089426
TI  - Evaluation of blood loss during limb salvage surgery for pelvic tumours.
AB  - As a large amount of blood loss is sometimes encountered in limb salvage
      procedures for pelvic tumours, it is essential to identify risk factors
      predicting the possibility of extensive haemorrhage. We retrospectively reviewed
      137 patients who underwent pelvic tumour resections. Patients with an estimated
      blood loss greater than 3,000 ml were classified as having a large amount of
      blood loss. Sixty-one (44.53%) patients had blood loss greater than 3,000 ml.
      Tumours involving the acetabulum or sacrum, tumour volume greater than 400 cm(3),
      aorta occlusion, resection method, reconstruction and operative time were all
      associated with a large amount of blood loss. Pelvic tumours involving the
      acetabulum or sacrum (odds ratio: 4.837), tumour volume greater than 400 cm(3)
      (odds ratio: 3.005) and planned operation time of more than 200 min (odds ratio:
      3.784) independently predicted a large amount of blood loss. Pelvic tumours with
      these characteristics were likely to have a large amount of blood loss during
      surgery.

PMID- 19089427
TI  - [Tumor profiling of renal cell tumors: relevance for diagnostics and therapy].
AB  - Molecular biological tumor markers and prognostic parameters are necessary for
      differential diagnosis, individual prognosis, and therapy in patients with renal
      cell tumors. By using high throughput technologies, it is possible to
      characterize tumor samples comprehensively. Based on specific genetic
      alterations, histopathological subtypes were defined as independent tumor
      entities. Genetic characteristics can be used for diagnosis of primary tumor
      samples and also of biopsies. Furthermore, specific molecular patterns of
      metastatic tumors are known, allowing the determination of the primary tumor's
      metastatic potential. The specific protein patterns of serum samples of tumor
      patients were analyzed, and several candidate proteins have been identified. One
      of these is SAA-1, which is elevated in patients with clear cell renal cell
      carcinomas (RCC). New therapeutic options are now available for patients with
      metastatic RCC. Therefore, it is necessary to select the best therapy for each
      patient and to detect therapy resistance very early. Biomarkers in tumor tissue
      and serum were found to correlate with therapy response.

PMID- 19089428
TI  - Dermatomyositis with hemorrhagic myositis.
AB  - A 64-year-old Japanese female, diagnosed as dermatomyositis with acute
      interstitial pneumonia, complained of acute abdominal pain. Computed tomography
      of the abdomen showed hematoma in the right retroperitoneum and left rectus
      sheath. Angiogram showed multiple small aneurysms on left iliolumbar artery and a
      horizontal linear flush, suggesting active bleeding foci in the muscles. Although
      arterial embolization therapy was effective for hemostatic treatment, she died of
      thrombotic thrombocytopenic purpura and multiple organ failure without
      respiratory insufficiency. Other causes of microaneurysm, such as systemic
      vasculitides or infectious diseases, were excluded. We considered that this is
      the first case report of dermatomyositis with hemorrhagic myositis associated
      with small aneurysms.

PMID- 19089429
TI  - Overexpression of lipid transfer protein (LTP) genes enhances resistance to plant
      pathogens and LTP functions in long-distance systemic signaling in tobacco.
AB  - The lipid signal is essential for the activation of plant defense responses, but
      downstream components of the signaling pathway are still poorly defined. To
      investigate the biological functions of pepper lipid transfer protein (LTP), we
      carried out virus-induced gene silencing (VIGS) in pepper, constitutive
      expression of CALTPs and grafting experiments in the tobacco plant. Suppression
      of endogenous CALTPI and CALTPII by VIGS, respectively, resulted in enhanced
      susceptibility to Xanthomonas campestris pv. vescatoria and pepper mosaic mottle
      virus in pepper. On the other hand, the constitutive expression of CALTPI and
      CALTPII genes in tobacco plants showed enhanced resistance to oomycete pathogen,
      Phytophthora nicotianae and bacterial pathogen, Pseudomonas syringae pv. tabaci.
      Enhanced resistance is found to be associated with the enhanced CALTP transcript
      levels in the independent transgenic CALTPI or II tobacco lines. Induced
      resistance responses in grafted scion leaves revealed that LTP plays a role in
      long-distance systemic signaling in plants.

PMID- 19089430
TI  - Italian multicenter, prospective study to evaluate the negative predictive value
      of 16- and 64-slice MDCT imaging in patients scheduled for coronary angiography
      (NIMISCAD-Non Invasive Multicenter Italian Study for Coronary Artery Disease).
AB  - This was a prospective, multicenter study designed to evaluate the utility of
      MDCT in the diagnosis of coronary artery disease (CAD) in patients scheduled for
      elective coronary angiography (CA) using different MDCT systems from different
      manufacturers. Twenty national sites prospectively enrolled 367 patients between
      July 2004 and June 2006. Computed tomography (CT) was performed using a
      standardized/optimized scan protocol for each type of MDCT system (> or =16
      slices) and compared with quantitative CA performed within 2 weeks of MDCT. A
      total of 284 patients (81%) were studied by 16-slice MDCT systems, while 66
      patients (19%) by 64-slice MDCT scanners. The primary analysis was on-site/off
      site evaluation of the negative predictive value (NPV) on a per-patient basis.
      Secondary analyses included on-site evaluation on a per-artery and per-segment
      basis. On-site evaluation included 327 patients (CAD prevalence 58%). NPV,
      positive predictive value (PPV), sensitivity, specificity, and diagnostic
      accuracy (DA) were 0.91 (95% CI 0.85-0.95), 0.91 (95% CI 0.86-0.95), 0.94 (95% CI
      0.89-0.97), 0.88 (95% CI 0.81-0.93), and 0.91 (95% CI 0.88-0.94), respectively.
      Off-site analysis included 295 patients (CAD prevalence 56%). NPV, PPV,
      sensitivity, specificity, and DA were 0.73 (95% CI 0.65-0.79), 0.93 (95% CI 0.87
      0.97), 0.73 (95% CI 0.65-0.79), 0.93 (95% CI 0.87-0.97), and 0.82 (95% CI 0.77
      0.86), respectively. The results of this study demonstrate the utility of MDCT in
      excluding significant CAD even when conducted by centers with varying degrees of
      expertise and using different MDCT machines.

PMID- 19089431
TI  - Dismembered pyeloplasty using double 'J' stent in infants and children.
AB  - PURPOSE: The purpose of the present study was to comprehensively assess the
      results of dismembered pyeloplasty in pelvi-ureteric junction obstruction (PUJO)
      using double 'J' ureteric stent. MATERIALS AND METHODS: Records of 61 dismembered
      pyeloplasties in 60 consecutive patients with PUJO who underwent pyeloplasty in a
      5-year period were reviewed retrospectively. In 58 cases, a double 'J' stent was
      passed in an antegrade fashion during the operation. No other mode of drainage
      was used. Stent was not placed on three occasions. Records were reviewed for age
      at diagnosis, age at surgery, post-operative complication, post-operative
      drainage and length of hospital stay. RESULTS: There were no episodes of urinary
      leak or re-obstruction in the stented group. Median post-operative stay in
      stented patients was 2 days. The use of this stent was associated with no serious
      complications. There were no episodes of post-operative urinary tract infection
      or stent displacement. CONCLUSIONS: We recommend double 'J' stent as the safest
      mode of drainage in pyeloplasty in infants and children. Keeping a double-J stent
      across the anastomosis reduces the complications and the hospital stay in these
      patients.

PMID- 19089432
TI  - Immunological investigation of the hepatic tissue from infants with biliary
      atresia.
AB  - PURPOSE: Matrix metalloproteinases (MMPs) and their endogenous tissue inhibitors
      [tissue inhibitors of metalloproteinases (TIMPs)] have been implicated in tissue
      injury and remodeling in many organs. The objective of this study was to evaluate
      the expression of MMP-3 and -9, and TIMP-1, -2, and -3 and their relationship to
      liver fibrosis in infants with biliary atresia. METHODS: The expression of MMP-3
      and-9 and TIMP-1, -2 and -3 was investigated in liver tissue samples of nine
      patients with biliary atresia. In addition, the expression of CCR-4 and CCR-5 was
      analyzed to investigate the activation of Th1 and Th2 cells. The mRNA levels were
      measured by semiquantitative reverse transcriptase polymerase chain reaction.
      RESULTS: The expression of MMP-3 was higher than that of MMP-9 in all samples (P
      < 0.01). The expression of TIMP-1 was higher than that of TIMP-2 and -3 in all
      samples (P < 0.01). The expression of CCR-5 was higher than that of CCR-4 (P <
      0.05), which implied higher activation of Th1 cells relative to Th2 cells.
      CONCLUSION: Our findings suggest that MMP-3, possibly induced by Th1 cytokines,
      and its balance with TIMP-1, may be one of the factors involved in the
      pathogenesis of biliary atresia.

PMID- 19089434
TI  - Colouterine fistula complicating diverticulitis in elderly women.

PMID- 19089433
TI  - Liver abscess in neonates.
AB  - INTRODUCTION: Liver abscesses are rare in neonates with the majority resulting
      from an ascending infection via the umbilical and portal veins, haematogenous
      spread, or via the biliary tree, or via direct contiguous spread from
      neighbouring structures. They may present in unusual ways often presenting with
      ongoing sepsis and resulting in diagnostic difficulties. We present the clinical
      and radiological findings on six neonates with hepatic abscesses and underline
      the association with misplacement of umbilical line, association with hypertonic
      glucose infusions and TPN. METHODS: A retrospective chart review made of six
      patients diagnosed with hepatic abscesses between 2000 and 2006. Methods included
      clinical and radiological review as well as evaluation of potential risk factors.
      RESULTS: Five of the six patients with neonatal liver abscess were of low birth
      weight and low gestational age (range 30-34 weeks), but one was post mature (42
      weeks). Sex distribution was equal and two were HIV exposed (mother positive),
      two HIV negative with two having an unknown HIV status. Clinical signs included
      raised infective markers (CRP) (6) and non-specific signs of septicaemia (4), but
      a tender hepatomegaly (1) and abdominal distension with ileus (1) were also
      noted. Five were right-sided abscesses (2 associated with malposition of
      umbilical line) and one central in position. Predisposing factors included
      association with a misplaced umbilical line with high concentration glucose
      infusions (2) and tuberculosis was later diagnosed in one. Infective markers
      (CRP) remained high with positive blood cultures persisting in all. Causative
      organisms included Klebsiella (3) Staphylococcus (3) [one a multi-resistant
      staphylococcus (MRSA)], Gonococcus (1) and Enterobacter (1). Abdominal X-ray
      demonstrated a mal-positioned umbilical line in three patients (50%). Ultrasound
      (US) proved a reliable method of diagnosis although some difficulty was
      encountered in interpreting resolving abscesses and trans-diaphragmatic spread
      occurred in one. Three patients (50%) responded to antibiotic therapy alone, but
      interventional drainage was required in the remainder. Needle aspiration was
      successful in two of these, but one further patient had a radiologically placed
      pigtail drainage, but later required open drainage. This patient then developed
      trans-diaphragmatic spread and empyema requiring thoracoscopic decortication.
      CONCLUSION: Neonatal hepatic abscesses are rare but should enter the differential
      diagnosis of a neonate with ongoing sepsis. This study serves to draw attention
      to their association with misplaced central (umbilical) catheters. Failure to
      respond to antibiotic therapy necessitates interventional drainage.

PMID- 19089435
TI  - Cytotoxic T lymphocyte antigen-4 promoter -658CT gene polymorphism is associated
      with ulcerative colitis in Chinese patients.
AB  - BACKGROUND AND AIM: Cytotoxic T lymphocyte antigen-4 (CTLA-4) plays a role in the
      downregulation of T cell activation. The present study aimed to examine an
      association between the CTLA-4 gene polymorphisms and ulcerative colitis (UC) in
      the Han Chinese in central China. MATERIALS AND METHODS: One hundred seventeen
      patients with UC and 246 healthy controls were genotyped for CTLA-4 gene -658CT
      in the promoter and CT61 at the 3' untranslated region using a method of
      polymerase chain reaction-based restriction fragment length polymorphism and
      single-strand conformation polymorphism, respectively. The distributions of the
      genotypes and the allele frequencies of the CTLA-4 gene in UC patients and
      healthy controls were compared by chi-square test. RESULTS: The frequency of the
      T/T+C/T genotype at the CTLA-4 gene -658CT in the promoter was significantly
      higher in UC patients than in healthy controls (26.5% vs 15.4%, chi (2) = 6.287,
      P = 0.015, OR = 1.973, 95%CI = 1.153-3.375). The frequency of the T allele at the
      CTLA-4 -658CT was also significantly higher in UC patients than in the controls
      (13.2% vs 8.1%, chi (2) = 4.707, P = 0.033, OR = 1.726, 95%CI = 1.049-2.838). The
      frequency of the T/T genotype at the -658 locus was highly associated with
      extensive colitis in UC patients (P = 0.037, OR = 3.955, 95%CI = 1.068-14.647).
      The frequency of the T allele at the -658 locus was highly associated with
      extensive colitis in UC patients (P = 0.0067, OR = 3.05, 95%CI = 1.320-7.048).
      CONCLUSION: The T allele of CTLA-4 -658 polymorphism in the promoter of CTLA-4
      gene was highly associated with UC in the Han Chinese in central China.

PMID- 19089437
TI  - Snapping elbow caused by hypertrophic synovial plica in the radiohumeral joint: a
      report of three cases and review of literature.
AB  - The snapping elbow caused by hypertrophic synovial radiohumeral plica is a rare
      form of lateral elbow impingement. In this article we report on hypertrophic
      radiohumeral synovial folds in three male patients, aged 54, 65 and 27 years. All
      three patients suffered isolated lateral elbow pain, painful snapping and
      unsuccessful conservative treatment over at least 5 months (range 5-9 months,
      mean 7.7 months) prior to surgical treatment. None of the patients had lateral
      epicondylitis, instability, osteochondrosis dissecans, loose bodies, arthritis or
      neurological disorders. Upon clinical examination the range of motion in the
      respective painful elbows was found to be normal in all three cases, but a
      painful snapping occurred between 80 degrees and 100 degrees of flexion with the
      forearm in pronation. While there were no pathologic findings in standard
      radiographs, magnetic resonance imaging (MRI) revealed hypertrophic synovial
      plicae in the radiohumeral joints associated with effusion in each of the
      diseased elbows. Arthroscopic examinations confirmed the presence of a
      hypertrophic synovial plica in all three radiocapitellar joints, and revealed a
      transient interposition and compression of the folds in the articulation from
      extension until 90 degrees -100 degrees elbow flexion, with replacement beyond 90
      degrees elbow flexion with a visible jump. Surgical management in all three cases
      comprised arthroscopic diagnosis confirmation and removal of the synovial plicae,
      leading to excellent outcomes at 6-12 months follow-up.

PMID- 19089438
TI  - The effects of betamethasone treatment on clinical and laboratory features of
      pregnant women with HELLP syndrome.
AB  - AIM: The present study aims to investigate the effects of betamethasone treatment
      on clinical outcome and laboratory data of pregnant women diagnosed with HELLP
      (hemolysis, elevated liver enzymes, and low platelet count) syndrome. METHODS: A
      prospective, randomized and placebo-controlled clinical trial was undertaken in a
      total of 60 pregnant women with HELLP syndrome who were treated at the
      perinatology department of the study center between January 2005 and February
      2008. Betamethasone treatment (intramuscular injection of 12 mg in every 24 h)
      was given to 30 subjects while remaining 30 subjects received placebo. The
      treatment and control groups were compared in the aspects of clinical outcome and
      laboratory data. RESULTS: The alterations in platelet counts, alanine
      aminotransferase, aspartate aminotransferase and lactate dehydrogenase levels of
      women treated with betamethasone were statistically similar to those of the
      placebo group. Although there was a significant decrease in diastolic blood
      pressure values of control group (P = 0.04), alterations in systolic blood
      pressure values were statistically indifferent in both study groups.
      Hematological and metabolic complications occurred significantly less in women
      treated with betamethasone (P < 0.05). Interestingly, the percentage of women who
      received platelet transfusion was significantly higher in the control group (P <
      0.005). No case of maternal mortality occurred. CONCLUSIONS: The betamethasone
      treatment has ended up with insignificant alterations in clinical outcomes and
      laboratory data of women with HELLP syndrome except beneficial effects on
      metabolic complications and need for platelet transfusion. Further investigation
      is required to assess the efficiency of betamethasone in management of HELLP
      syndrome.

PMID- 19089439
TI  - "GenderPlex" a PCR multiplex for reliable gender determination of degraded human
      DNA samples and complex gender constellations.
AB  - The amelogenin test integrated in most commercial polymerase chain reaction (PCR)
      multiplex kits is routinely used in the forensic field for gender determination
      of DNA samples. It has been demonstrated that this test is not entirely reliable.
      Males with deletions in the homologous amelogenin part on the Y chromosome
      (AMELY) were erroneously typed as females due to lack of Y-specific amelogenin
      amplification. Also, primer binding site mutations that result in a failure to
      amplify the AMELY or the X-chromosomal part (AMELX) have been observed. For
      clarification of such phenomena, a new PCR multiplex (GenderPlex) is presented,
      co-amplifying two different regions of the amelogenin gene (55/58 and 106/112 bp
      for the AMELX and AMELY alleles, respectively), a 93-bp sequence stretch of the
      SRY gene and four mini-X-STR loci DXS7424, DXS8378, DXS6803 and GATA172D05
      (maximum product size less than 140 bp). This strategy helps with the evaluation
      of samples for the presence of amelogenin-based primer site mutations and
      confirms a male genotype by the absence of heterozygote X-STR alleles and the
      presence of an SRY-related peak. The short amplicon sizes of all involved loci
      proved to be beneficial in a study on artificially degraded DNA. Furthermore, we
      demonstrate by means of sensitivity, human specificity and mixture studies that
      the multiplex is suitable for investigations in the forensic scene. Finally, the
      performance of the GenderPlex was evaluated on a west Eurasian population sample
      from Austria comprising 166 male and 104 female individuals.

PMID- 19089440
TI  - Distance doubling visual acuity test: a reliable test for nonorganic visual loss.
AB  - BACKGROUND: To determine the value of the distance doubling visual acuity test in
      the diagnosis of nonorganic visual loss in a comparative observational case
      series. METHODS: Twenty-one consecutive patients with nonorganic visual acuity
      loss and 21 subjects with organic visual loss as controls were included. Best
      corrected visual acuity was tested at the normal distance of 5 meters using
      Landolt Cs. The patient was then repositioned and best corrected visual acuity
      was tested with the previous optotypes at double the distance via a mirror.
      RESULTS: Nonorganic visual acuity loss was identified in 21 of 21 patients.
      Sensitivity and specificity of distance-doubling visual acuity test in functional
      visual loss were found to be 100% (CI; 83%-100%) and 100% (CI; 82%-100%),
      respectively. CONCLUSION: Distance doubling visual acuity test is widely used to
      detect nonorganic visual loss. Our results show that this test has a high
      specificity and sensitivity to detect nonorganic visual impairment.

PMID- 19089441
TI  - Analysis of the vitreous membrane in a case of type 1 Stickler syndrome.
AB  - BACKGROUND: Stickler syndrome causes ocular abnormalities, including retinal
      detachment and vitreoretinal degeneration, and systemic anomalies such as
      arthritis and deafness. Although retinal detachment is characteristic of this
      syndrome, the pathogenesis is unknown. CASE REPORT: A 10-year-old boy reported
      decreased vision and presented 5 days after visual loss. RESULTS: Ophthalmoscopy
      showed a retinal detachment with a giant tear in the right eye, and a
      nonpigmented epithelial detachment with pars plicata breaks in the left eye.
      Bilateral findings included an empty vitreous and a vitreous membrane at the
      equator. The systemic abnormalities included short stature and joint
      hypermobility. The diagnosis was type 1 Stickler syndrome, and the eyes were
      treated surgically. Immunohistochemistry showed that the vitreous membrane
      resected intraoperatively was comprised primarily of Muller cells. Electron
      microscopy showed dense collagen fibers around the cells in the membrane that
      were identical to the vitreous collagen inserted into the basement membrane of
      the cells, which was similar to the ultrastructure of the vitreous base.
      CONCLUSION: Muller cells might be primary components of the vitreous membrane in
      type 1 Stickler syndrome. The vitreoretinal interface, which resembled the
      ectopic vitreous base, in the vitreous membrane may be related to the
      pathogenesis of the retinal detachment.

PMID- 19089442
TI  - Indocyanine green enhanced subthreshold diode-laser micropulse photocoagulation
      treatment of chronic central serous chorioretinopathy.
AB  - PURPOSE: To assess the efficacy and safety of indocyanine green (ICG) dye
      enhanced subthreshold diode-laser micropulse (SDM) photocoagulation in patients
      with chronic central serous chorioretinopathy (CCSC) with no spontaneous
      resolution 6 months after the onset of the disease. STUDY DESIGN: Interventional
      prospective non-comparative case series of seven patients presenting with CCSC
      with well-defined active leaking sites (ALS) suitable for laser treatment and
      with serous neuroepithelial detachment persisting for 6 or more months. METHODS:
      SDM treatment was performed 15 minutes after the injection of 25 mg of ICG in 2
      cc of 5% glucose solution. ALS were treated with a series of 50 500-ms exposures
      separated by 500-ms pauses. Each 500-ms exposure delivered a train of 250
      micropulses at 10% duty cycle and 500 mW power. ICG angiographic images were
      taken after the treatment without new ICG injection, to check for the presence of
      laser-induced spots of background hypofluorescence at the treated leakage sites.
      RESULTS: Within 7-14 days after treatment, all the patients showed improved
      visual acuity and reduction of serous neuroepithelial detachment on OCT. No signs
      of laser lesions were visible at fundus examination and on fluorescein
      angiography. In a period ranging from 4 to 8 weeks, the neuroepithelial
      detachment was completely resolved in five patients and reduced in two patients.
      At the 12-month follow-up visits, no recurrence had occurred in the patients,
      with resolution of the serous neuro-epithelial detachment, and no worsening of
      the serous detachment or of VA was noted in the patients with incomplete
      recovery. CONCLUSIONS: These preliminary results suggest that ICG dye-enhanced
      SMD photocoagulation appears to be an effective treatment, and can represent a
      viable approach for the management of CSCC with persistent serous neuroepithelial
      detachment. Post-treatment ICG angiography, without new ICG dye injection, can be
      used to verify the placement of the SDM laser applications.

PMID- 19089443
TI  - An early "reopening" case of idiopathic macular hole; supportive usefulness of
      fundus autofluorescence.
AB  - BACKGROUND: Anatomical closure of macular holes (MH) is now largely confirmed by
      optical coherence tomography (OCT). Fundus autofluorescence (FAF) is also helpful
      in diagnosis and anatomical estimation of MH. We report a case of early reopening
      of anatomically closed MH, 2 days after release from face-down positioning where
      FAF abnormalities proceeded OCT findings. METHODS: A case report. A 67-year-old
      woman underwent vitrectomy with brilliant blue G-assisted ILM peeling for the
      treatment of full-thickness stage 4 MH (diameter 578 microm). FAF and OCT were
      used to evaluate the patient. RESULTS: On post operative day 3, OCT showed
      anatomical closure of MH, but FAF persistently demonstrated hyperfluorescence in
      the fovea. On post operative day 5, 2 days after termination of positioning, OCT
      showed reopening of the MH. Intra-vitreous injection of 50 % sulfur hexafluoride
      (SF(6)) gas was performed followed by face-down positioning again. Fourteen days
      after surgery, we confirmed the findings of both the anatomical closure in OCT
      and hypofluorescence on FAF. Two months later, MH remained closed. CONCLUSIONS:
      FAF might be a useful measure as a supportive method to guide release from
      posture restriction.

PMID- 19089444
TI  - Exercise modality and physical fitness in perimenopausal women.
AB  - The effect of exercise modalities on determinants of sarcopenia, specifically,
      lean tissue mass, maximal voluntary isometric contraction (MVIC), muscle quality
      (MQ), and cardiorespiratory fitness (VO(2)peak) over 12 weeks were studied in 42
      (45-55 years, 60 days of amenorrhea, with </=1 h/week physical activity)
      perimenopausal females. Subjects were assigned to strength training (super-slow,
      20 s tension, ST(ss) = 7; hypertrophy, 2-4 s tension, ST(ht) = 8), endurance
      training (intermittent, >/=48 h rest, ET(i) = 7; consecutive, 24 h, ET(c) = 9)
      and autogenic training group (AT = 11). ST and ET met 60 min day(-1), 3 days
      week(-1) and AT 1 day week(-1). Leg extension, incremental cycling with gas
      exchange, dual-energy X-ray absorptiometry, and blood analysis were tested. The
      MANOVA revealed that ST(ss) improved MVIC (P < 0.01) and MQ (P </= 0.01). The
      VO(2)peak also increased significantly in ET group by 28% (ET(i): P = 0.02,
      ET(c): P = 0.01). A modality-specific effect on strength, MQ, and VO(2)peak in
      perimenopausal females was duly noted.

PMID- 19089445
TI  - Computational object recognition: a biologically motivated approach.
AB  - We propose a conceptual framework for artificial object recognition systems based
      on findings from neurophysiological and neuropsychological research on the visual
      system in primate cortex. We identify some essential questions, which have to be
      addressed in the course of designing object recognition systems. As answers, we
      review some major aspects of biological object recognition, which are then
      translated into the technical field of computer vision. The key suggestions are
      the use of incremental and view-based approaches together with the ability of
      online feature selection and the interconnection of object-views to form an
      overall object representation. The effectiveness of the computational approach is
      estimated by testing a possible realization in various tasks and conditions
      explicitly designed to allow for a direct comparison with the biological
      counterpart. The results exhibit excellent performance with regard to recognition
      accuracy, the creation of sparse models and the selection of appropriate
      features.

PMID- 19089446
TI  - Portal vein stenting the first day after orthotopic liver transplantation for
      residual postthrombotic stenosis compromising portal flow.
AB  - BACKGROUND: Early portal vein impairment or thrombosis after liver
      transplantation is a significant risk factor for graft failure. CASE: Here, we
      describe a case of severe portal hypoperfusion after thrombectomy during liver
      transplantation that was treated with percutaneous stenting on the first
      postoperative day. Stenting was combined with embolization of varices and
      normalized portal inflow. RESULT: Liver function and portal flow were normal
      after 1 year of follow-up. CONCLUSION: This case demonstrates that percutaneous
      stenting is a safe and feasible therapeutic option even in the initial days after
      liver transplantation.

PMID- 19089447
TI  - Evolutionary origin and phylogenetic analysis of the novel oocyte-specific
      eukaryotic translation initiation factor 4E in Tetrapoda.
AB  - The transcriptionally active, growing oocyte accumulates mRNAs essential for
      early stages of development, the oocyte-to-embryo transition, in a stable,
      dormant form. Translational repression of mRNAs in eggs of various species is
      conferred by interactions, either direct or via intermediate proteins, of
      repressive factors bound to the 3'-untranslated regions with the proteins of the
      eukaryotic translation initiation factor 4E (eIF4E) family bound to the 5'-cap of
      the transcripts. Recently, a novel oocyte-specific eIF4E encoded by the Eif41b
      gene in mammals has been identified by our group. To further investigate this
      gene, the available cDNA libraries, as well as genome assemblies of nonmammalian
      vertebrates, were surveyed. This analysis revealed that the Eif4e1b gene arose in
      Tetrapoda as a result of the ancestral Eif4e locus duplication. Unlike other
      known proteins of three subfamilies comprising eIF4E family (eIF4E1, eIF4E2, and
      eIF4E3), cDNA library evidence suggests that Eif41b locus has an oocyte
      restricted expression across all classes of Tetrapoda. To further understand the
      role of eIF4E1B during oocyte maturation, injections of antisense morpholino
      nucleotides in the X. tropicalis fully-grown stage VI oocytes were performed. The
      resulted ablation of eIF4E1B protein led to significant acceleration of oocyte
      maturation after progesterone induction; morpholino-injected oocytes formed the
      metaphase plate 30 min faster than the control groups. These results suggest that
      eIF4E1B protein acts as a repressor in translational regulation of maternal mRNAs
      activated during, and required for, oocyte maturation.

PMID- 19089448
TI  - Family-based group treatment versus individual treatment in the management of
      childhood obesity: randomized, prospective clinical trial.
AB  - INTRODUCTION: This study assessed the short- and long-term effects of a 3-month
      family-based group treatment in the management of childhood obesity versus
      individual treatment. MATERIALS AND METHODS: Eighty obese children, aged between
      6 and 14 years, and their parents were included in this prospective controlled
      clinical study. Forty participants were randomly assigned for group treatment and
      the other 40 for individual treatment. A 3-month intervention program was focused
      on implementing healthy eating behaviors. The weight and height of the children
      were measured initially and at each treatment session and at follow-up visits.
      Body mass index was calculated and expressed as standard deviation score. RESULTS
      AND DISCUSSION: At the end of 3-month treatment program, there was a significant
      decline in BMI SDS in both groups (p < 0.001). After 1 year of follow-up period,
      there was still a significant decrease in BMI SDS in the study group (p < 0.001),
      whereas the decrease in BMI SDS was not maintained over the follow-up period in
      the standard group. There was a significantly increased consumption of vegetable
      and fruit and reduced consumption of carbonated drinks and fruit juice in both
      groups (p < 0.001). CONCLUSION: These findings demonstrate that the group
      treatment is more successful than the individual treatment in the management of
      childhood obesity.

PMID- 19089449
TI  - Prevalence of congenital heart defects in neuroblastoma patients: a cohort study
      and systematic review of literature.
AB  - Data on the prevalence of congenital heart defects (CHD) in neuroblastoma
      patients are inconsistent. If CHD are more common in neuroblastoma patients than
      in the general population, cardiac screening might be warranted. In this study we
      used echocardiography to determine the prevalence of CHD in a single centre
      cohort of surviving neuroblastoma patients. In addition, we performed a
      systematic review of the literature. Echocardiography was performed in 119 of 133
      patients (89.5%). Only two patients (1.7%) had CHD. The prevalence of CHD was not
      significantly different from a previously published control group of 192
      leukaemia patients examined by echocardiography (P = 0.49). Literature search
      revealed 17 studies, showing prevalence rates of CHD in neuroblastoma patients
      ranging from 0 to 20%. Prevalence was less than 3.6% in the majority of studies.
      Most studies lacked information on validity. We conclude that current evidence
      does not support standard cardiac screening in all patients with neuroblastoma.

PMID- 19089450
TI  - A simple method for long-term storage of Acanthamoeba species.
AB  - We present a novel and simple technique for storing live Acanthamoeba for long
      periods of time. The amoebae are maintained at refrigerator temperatures in a
      peptone-yeast extract-glucose (PYG) medium normally used for cultivation. Using
      this method, we obtained survival rates of at least 4 years for Acanthamoeba
      polyphaga and 3 years for Acanthamoeba castellanii and Acanthamoeba rhysodes.
      Advantages of this storage method are: (1) it is quick and simple, (2)
      inexpensive, (3) does not require encystment before storage, (4) resuscitation of
      cysts can be achieved within a week of culture in PYG medium at 27 degrees C, and
      does not require co-culture with bacteria or any special equipment.

PMID- 19089451
TI  - Eimeria tenella microneme protein EtMIC4: capture of the full-length transcribed
      sequence and comparison with other microneme proteins.
AB  - EtMIC4 is a microneme protein of Eimeria tenella, an intracellular apicomplexan
      protozoan that can cause severe enteritis in chickens. The EtMIC4 gene has been
      partially characterised, and in this study, we used a combined strategy of rapid
      amplification of cDNA ends (5'RACE) and reverse transcription-polymerase chain
      reaction to identify the authentic 5' end of the transcribed sequence (accession
      number AJ306453.2). Comparison of the predicted EtMIC4 transcription start site
      with predicted start sites for EtMIC1, 2 and 3 genes identified comparable
      initiator regions that each conform to the consensus sequence for a
      transcriptional initiator element. The EtMIC4 gene is organised over 11 exons and
      analysis of the full-length predicted protein identified a new N-terminal region
      that comprises a hydrophobic signal peptide followed by four thrombospondin-type
      1 modules that are similar to those previously described further downstream in
      the protein. Best-fit analysis shows that EtMIC4 shares high homology with the
      Eimeria maxima protein EmTFP250 and with TgMIC12, a predicted Toxoplasma gondii
      microneme protein. EtMIC4 and EmTFP250 share 70% amino acid identity and all
      predicted structural domains are conserved between the two. EtMIC4 and TgMIC12
      share 48% identity and they have very similar domain organisation and
      conservation of intron/exon boundaries.

PMID- 19089453
TI  - A comprehensive evaluation of SNP genotype imputation.
AB  - Genome-wide association studies have contributed significantly to the genetic
      dissection of complex diseases. In order to increase the power of existing marker
      sets even further, methods have been proposed to predict individual genotypes at
      un-typed loci from other marker sets by imputation, usually employing HapMap data
      as a reference. Although various imputation algorithms have been used in practice
      already, a comprehensive evaluation and comparison of these approaches, using
      genome-wide SNP data from one and the same population is still lacking. We
      therefore investigated four publicly available programs for genotype imputation
      (BEAGLE, IMPUTE, MACH, and PLINK) using data from 449 German individuals
      genotyped in our laboratory for three genome-wide SNP sets [Affymetrix 5.0 (500
      k), Affymetrix 6.0 (1,000 k), and Illumina 550 k]. We observed that HapMap-based
      imputation in a northern European population is powerful and reliable, even in
      highly variable genomic regions such as the extended MHC on chromosome 6p21.
      However, while genotype predictions were found to be highly accurate with all
      four programs, the number of SNPs for which imputation was actually carried out
      ('imputation efficacy') varied substantially. BEAGLE, IMPUTE, and MACH yielded
      nearly identical trade-offs between imputation accuracy and efficacy whereas
      PLINK performed consistently poorer. We nevertheless recommend either MACH or
      BEAGLE for practical use because these two programs are more user-friendly and
      generally require less memory than IMPUTE.

PMID- 19089452
TI  - Identification of genomic regions contributing to etoposide-induced cytotoxicity.
AB  - Etoposide is routinely used in combination-based chemotherapy for testicular
      cancer and small-cell lung cancer; however, myelosuppression, therapy-related
      leukemia and neurotoxicity limit its utility. To determine the genetic
      contribution to cellular sensitivity to etoposide, we evaluated cell growth
      inhibition in Centre d' Etude du Polymorphisme Humain lymphoblastoid cell lines
      from 24 multi-generational pedigrees (321 samples) following treatment with 0.02
      2.5 microM etoposide for 72 h. Heritability analysis showed that genetic
      variation contributes significantly to the cytotoxic phenotypes (h (2) = 0.17
      0.25, P = 4.9 x 10(-5)-7.3 x 10(-3)). Whole genome linkage scans uncovered 8
      regions with peak LOD scores ranging from 1.57 to 2.55, with the most significant
      signals being found on chromosome 5 (LOD = 2.55) and chromosome 6 (LOD = 2.52).
      Linkage-directed association was performed on a subset of HapMap samples within
      the pedigrees to find 22 SNPs significantly associated with etoposide
      cytotoxicity at one or more treatment concentrations. UVRAG, a DNA repair gene,
      SEMA5A, SLC7A6 and PRMT7 are implicated from these unbiased studies. Our findings
      suggest that susceptibility to etoposide-induced cytotoxicity is heritable and
      using an integrated genomics approach we identified both genomic regions and SNPs
      associated with the cytotoxic phenotypes.

PMID- 19089454
TI  - Chondrocyte apoptosis enhanced at the growth plate: a physeal response to a
      diaphyseal fracture.
AB  - Post-traumatic overgrowth of growing long bones is a common clinical phenomenon
      in paediatric traumatology and is the result of an enhanced stimulation of the
      nearby growth plate after fracture. To date, the exact post-fractural reactions
      of the growth plate are poorly understood. The aim of this study has been to
      determine the impact of fracture on the frequency of chondrocyte apoptosis of the
      growth plate. Rats sustained a mid-diaphyseal closed fracture of the left tibia
      or were left untreated. All animals were killed 3, 10, 14 or 29 days after
      trauma. The left and right tibiae were harvested and apoptotic chondrocytes of
      the proximal tibial growth plate were detected by TUNEL staining. The apoptosis
      percentage of physeal chondrocytes was statistically compared among fractured
      bones, intact contra-lateral bones and control bones. The physeal apoptosis rate
      of the fractured bone was significantly higher than that of the contra-lateral
      intact bone (valid for all evaluated days) and the control bone (valid from day
      10 onwards). Contra-lateral intact tibiae never showed significantly higher
      apoptosis rates compared with control tibiae. Thus, mid-diaphyseal fracture
      influences the nearby growth plate by stimulating chondrocyte programmed cell
      death, which is associated with cartilage resorption and bone replacement. The
      lack of a significant difference between the intact contra-lateral and the intact
      control bone suggests that fracture only has a local effect that contributes to
      the greater apoptosis rate of the adjacent physis.

PMID- 19089455
TI  - In vitro decidualization of rat endometrial stromal cells.
AB  - The induction of the decidualization of endometrial stromal cells is possible in
      an in vitro cell culture system. However, thus far, methods differ according to
      species or cell type, and a more stable or universal system has not yet been
      developed. The purpose of the present study has been to establish an in vitro
      decidualization system in primary cultured rat endometrial stromal cells (RES).
      The RES were treated with medroxyprogesterone acetate and dibutyryl-cyclic
      adenosine monophosphate (MPA treatment), estradiol and progesterone, or
      arachidonic acid. After 24 h of treatment, cells responded to all of the
      stimulations by expressing desmin mRNA. However, decidual/trophoblast prolactin
      related protein (dPRP) mRNA was only expressed in the MPA-treated cells. Desmin
      and dPRP mRNA were not expressed after MPA treatment of the RES derived from
      immature rat uteri. However, mRNA from both desmin and dPRP were expressed in RES
      derived from gonadotrophin-injected immature rats. The expression of matrix
      metalloproteinase-2 (MMP-2) and MMP-9 mRNA did not change after the decidual
      treatment of RES examined by real-time polymerase chain reaction. However, the
      results of gelatin zymography showed that the active forms of MMP-2 and MMP-9
      significantly increased after in vitro decidualization (P < 0.05). We conclude
      that MPA treatment is the most effective method for stimulating decidualization
      in RES. Use of this system has revealed that sexual maturation and gonadotrophins
      are important for RES with regard to decidualization. Furthermore, the activity
      of MMP-2 and MMP-9 might increase during decidualization without a corresponding
      increase of the expression of these genes.

PMID- 19089456
TI  - Gene and microRNA expression signatures of human mesenchymal stromal cells in
      comparison to fibroblasts.
AB  - Human mesenchymal stromal cells (MSCs) offer great hope for the treatment of
      tissue degenerative and immune diseases, but their phenotypic similarity to
      dermal fibroblasts may hinder robust cell identification and isolation from
      diverse tissue harvests. To identify genetic elements that can reliably
      discriminate MSCs from fibroblasts, we performed comparative gene and microRNA
      expression profiling analyses with genome-wide oligonucleotide microarrays. When
      taken globally, both gene and microRNA expression profiles of MSCs were highly
      similar to those of fibroblasts, accounting well for their extensive phenotypic
      and functional overlaps. Scattered expression differences were pooled to yield an
      MSC-specific molecular signature, consisting of 64 genes and 21 microRNAs whose
      expressions were at least 10-fold and two-fold higher, respectively, in MSCs
      compared with fibroblasts. Genes either encoding transmembrane proteins or
      associated with tumors were relatively abundant in this signature. These data
      should provide the molecular basis not only for the discovery of novel diagnostic
      markers discriminating MSCs from fibroblasts, but also for further studies on MSC
      specific signaling mechanisms.

PMID- 19089457
TI  - Maternal and individual effects in selection of bed sites and their consequences
      for fawn survival at different spatial scales.
AB  - We examined the relationship between survival of roe deer (Capreolus capreolus)
      fawns at Trois Fontaines, Champagne-Ardennes, France, and factors related to bed
      site selection (predator avoidance and thermoregulation) and maternal food
      resources (forage availability in the maternal home range). Previous studies have
      demonstrated that at small scales, the young of large herbivores select bed sites
      independently from their mothers, although this selection takes place within the
      limits of their mother's home range. Fawn survival was influenced largely by the
      availability of good bed sites within the maternal home range, not by the fawn's
      selection of bed sites; however, selection for thermal cover when selecting bed
      sites positively influenced survival of young fawns. Typical features of a good
      home range included close proximity to habitat edges, which is related to forage
      accessibility for roe deer. The availability of bed sites changed as fawns aged,
      probably due to an increased mobility of the fawn or a different use of the home
      range by the mother; sites offering high concealment and thermal protection
      became less available in favor of areas with higher forage accessibility. Despite
      the minor influence of bed-site selection on survival, roe deer fawns strongly
      selected their bed sites according to several environmental factors linked to
      predator avoidance and thermoregulation. Fawns selected for sites providing
      concealment, light penetration, and avoided signs of wild boar (Sus scrofa)
      activity. Avoidance of sites with high light penetration by young fawns
      positively affected their survival, confirming a negative effect on
      thermoregulation due to reduced thermal cover. Selection for light penetration by
      older fawns was less clear. We discuss these results in the context of cross
      generational effects in habitat selection across multiple scales, and the
      potential influence of the 'ghost of predation past'.

PMID- 19089458
TI  - Renal manifestations in toddlers with Takayasu's arteritis and malignant
      hypertension.
AB  - Three children under the age of 3 years presented with malignant hypertension,
      proteinuria, and acute kidney injury. Takayasu's arteritis was diagnosed on the
      basis of clinical symptoms of weight loss and low grade fever in conjunction with
      elevated sedimentation rate and radiographic evidence of aortic and renal artery
      stenosis. One patient had a renal biopsy which showed arteriolar sclerosis and
      focal glomerulosclerosis. All three patients required multiple antihypertensive
      agents, ultimately including angiotensin receptor blockers and/or angiotensin
      converting enzyme inhibitors. The vasculitis was treated with pulse
      corticosteroids followed by cyclophosphamide in one patient and mycophenolate
      mofetil as maintenance therapy in all. Follow-up has ranged from 2 to 8 years.
      Although global renal function has normalized in each patient, two have
      unilateral non-function of one kidney. The last patient has persistent aortic and
      renal artery stenosis with complex collateralization requiring ongoing medical
      and anticipated surgical management.

PMID- 19089459
TI  - The Medical Care Continuity (MCC) project. A pilot study of video-assisted home
      care within the eTEN European Community program. The Italian experience.
AB  - GOALS OF WORK: This study aimed to use an integrated system (Medical Care
      Continuity (MCC) system) consisting of computer, video telephone, and a high
      definition camera to monitor at home chemotherapy side effects in cancer
      outpatients. PATIENTS AND METHODS: The system allowed 24 h/day video consultation
      with an intermediate medical call center with possible connection to a
      specialized hospital if necessary. All patients were provided with
      internationally validated and project-oriented questionnaires exploring patients'
      health status and opinions on usefulness and complexity of study devices. The
      content of each call was recorded on a computer database. An approximate estimate
      of avoided hospital admissions was calculated. MAIN RESULTS: Median duration of
      experimentation and frequency of patient/doctor contacts were 2.1 months and 4.2
      contact per week, respectively. Overall, a 98% positive opinions on the
      experimental system was reported at the end of the study by all participants,
      with a 21% conversion rate with respect to the opinions gathered at study entry.
      Changes in patient management after a medical call were made in 32% of cases. It
      was calculated that approximately 2.2 per month unnecessary hospital admissions
      were avoided. CONCLUSIONS: The MCC system was well managed by both patients and
      caregivers. These results show that it has the potential to improve medical
      assistance by virtue of a constant access to medical advice and reduce
      unnecessary hospital admissions.

PMID- 19089460
TI  - Transforming the experience of cancer care: a qualitative study of a hospital
      based volunteer psychosocial support service.
AB  - PURPOSE: As volunteer support services for cancer patients evolve and seek to
      gain credibility and acceptance, it is important that these services be carefully
      evaluated. This paper describes findings from a research study conducted by the
      Healing Beyond the Body (HBB) program, a hospital-based volunteer psychosocial
      support service in a comprehensive cancer center in Toronto, Canada. The goal of
      this study was to gain insight into the experience of patients who have
      interacted with HBB volunteers and to evaluate the benefits and risks of this
      program for these patients. MATERIALS AND METHODS: A qualitative research method,
      based on semi-structured interviews with 15 patients recruited in the
      Chemotherapy Daycare Unit, was used. The interviews were transcribed and
      thematically analyzed. RESULTS: Findings suggest that volunteers can effectively
      serve an enhanced supportive role in a hospital setting without adverse effects,
      and that their services are positively received by patients. The following themes
      were identified in relation to perceived benefits of the HBB volunteer support
      service: (1) a sense of humanization and normalization; (2) a sense of security;
      (3) support for non-medical needs; and (4) support for unaccompanied patients.
      While no negative experiences with the HBB volunteers were reported, the
      following themes were identified in relation to potential weaknesses of the HBB
      volunteer service: (1) a limited awareness by patients of the HBB volunteers'
      roles and responsibilities; and (2) the lack of a structured role definition for
      the HBB volunteers at the pre-treatment phase. CONCLUSION: Our findings add to
      the literature on the contribution of volunteer support services and may serve
      decision-makers concerned with best practices in utilizing volunteer resources
      within a cancer hospital structure.

PMID- 19089461
TI  - Resounding attachment: cancer inpatients' song lyrics for their children in music
      therapy.
AB  - GOALS OF WORK: Scant attention focuses on supporting parent-child communication
      during the parents' cancer hospitalizations. Parents may struggle to remain
      emotionally available. Caregiver absences may threaten secure attachment
      relationships with infants and elicit problems amongst older children. Music
      therapists help many parents with cancer to compose songs for their children.
      Their lyric analysis may provide insight into song writing's communicative and
      therapeutic potential. MATERIALS AND METHODS: Two song lyric groups were
      comparatively analyzed (based on grounded theory). One group included 19 songs
      written by 12 patients with the first author. Another included 16 songs written
      by 15 patients with three music therapists (including two authors), which were
      previously published or recorded for the public. Songs were composed by 20
      mothers and seven fathers for at least 46 offspring. All parents had
      hematological or metastatic diseases. Qualitative inter-rater reliability was
      integrated. MAIN RESULTS: Comparable lyrical ideas in the two parent song groups
      included: love; memories; yearning for children; metaphysical presence (now and
      afterlife); loss and grief; the meaning and helpfulness of the children in their
      lives; hopes for and compliments about their children; encouragement; requests;
      personal reflections; existential beliefs; and suggestions about to whom the
      children can turn. CONCLUSIONS: Parents' song lyric messages may support their
      children during the parents' illnesses and through the children's developmental
      transitions and possible bereavement. Some parents use song writing for catharsis
      and to encourage their children's continuing attachment with them after death.
      Through promoting parent-child connectedness and emotional expression,
      therapeutic song writing can be a valuable oncologic supportive care modality.

PMID- 19089462
TI  - Risk of renal impairment after treatment with ibandronate versus zoledronic acid:
      a retrospective medical records review.
AB  - PURPOSE: This retrospective study compared renal impairment rates in breast
      cancer, multiple myeloma, prostate cancer and non-small cell lung cancer patients
      treated with ibandronate or zoledronic acid. STUDY DESIGN: Medical records in two
      German oncology clinics from May 2001 to March 2006 were retrospectively
      reviewed. Creatinine measurements were analyzed from baseline (before
      bisphosphonate treatment) to last available measurement for each patient. The Cox
      proportional hazards model and the Andersen-Gill extension of the Cox model for
      multiple events analysis were used for multivariate analysis, which controlled
      for age, clinic site, primary cancer type, baseline SCr or GFR value, prior
      bisphosphonate use, concomitant use of drugs associated with acute renal failure,
      and renal-related comorbidities. RESULTS: Of 333 patients, 109 received
      ibandronate and 256 received zoledronic acid (32 patients had both drugs).
      Compared with ibandronate, the zoledronic acid group had a significantly better
      baseline renal function and fewer patients had a history of renal disease.
      Zoledronic acid treatment increased the relative risk (RR) and the incidence rate
      (IR) of renal impairment by approximately 1.5-fold in all assessed patients (all
      tumors) compared with ibandronate. Multivariate analysis found significantly
      higher hazards ratios for zoledronic acid over ibandronate (two to sixfold),
      after adjusting for differences in characteristics between the two treatment
      groups. CONCLUSIONS: In this retrospective review, patients were significantly
      more likely to experience renal impairment with zoledronic acid than with
      ibandronate.

PMID- 19089463
TI  - Prospective assessment of chemotherapy-induced peripheral neuropathy due to
      weekly paclitaxel in patients with advanced or metastatic breast cancer (CSP-HOR
      02 study).
AB  - GOALS OF WORK: The aim of this study was to prospectively evaluate chemotherapy
      induced peripheral neuropathy (CIPN) using a patient-based instrument, the
      Patient Neurotoxicity Questionnaire (PNQ) and a physician-based instrument, the
      National Cancer Institute-Common Toxicity Criteria (NCI-CTC) in patients with
      advanced or metastatic breast cancer who were treated with weekly paclitaxel.
      MATERIALS AND METHODS: CIPN symptoms were prospectively assessed in 35 patients
      using the PNQ, NCI-CTC, and the Functional Assessment of Cancer Therapy (FACT)
      Taxane including neurotoxicity component (Ntx) at the baseline, and 8 and 16
      weeks after starting chemotherapy. RESULTS: For sensory neuropathy symptoms, the
      reported incidence of CIPN was significantly increased during active treatment in
      terms of both the PNQ and NCI-CTC assessments. In contrast, there was a notable
      increase of patient motor neuropathy symptoms that were elucidated only by the
      PNQ. The PNQ grades of CIPN were widely distributed in the patient population as
      compared with the NCI-CTC grades for both sensory and motor neuropathy. The
      sensory PNQ grade was correlated with sensory NCI-CTC grade (r = 0.58) and Ntx (r
      = 0.51), and the motor PNQ grade was correlated with Ntx (r = 0.57). CONCLUSIONS:
      The PNQ appears to be more sensitive and responsive than the NCI-CTC for CIPN;
      the PNQ appears to have diagnostic validity for evaluating CIPN in patients who
      are receiving neurotoxic chemotherapy.

PMID- 19089464
TI  - Lumbar lordosis in osteoporosis and in osteoarthritis.
AB  - The curvature of the lumbar spine and the risk of developing either osteoporosis
      (OP) or osteoarthritis (OA) are influenced by many common factors. The aim of
      this study is to determine whether lumbar lordosis is different between patients
      with either disease and healthy persons. A cross-sectional, blinded, controlled
      design was implemented. One hundred and twelve postmenopausal women were
      evaluated for bone mineral density as well as undergoing spinal radiography.
      Lordosis measurement was performed with Cobb's method. The sample was divided in
      four groups: patients with OP (n = 34, L1-L5 = 40.7 degrees, L1-S1 = 54.1
      degrees), patients with OA (n = 29, L1-L5 = 38 degrees, L1-S1 = 52.3 degrees),
      patients with both diseases (n = 20, L1-L5 = 41.8 degrees, L1-S1 = 52.3 degrees)
      and controls (n = 29, L1-L5 = 38.6 degrees, L1-S1 = 51.8 degrees). For all
      participants age, height, weight, body mass index, physical activity level and
      basal metabolic rate were measured and recorded. The results revealed that
      although the four groups have significant constitutional differences, lumbar
      lordosis was comparable between them. The reasons for the lack of association are
      discussed.

PMID- 19089465
TI  - Postoperative aseptic osteonecrosis in a case of kyphoplasty.
AB  - Aseptic osteonecrosis appears to be an infrequent adverse event after kyphoplasty
      which has not previously been reported. In the following, we present the case of
      a 73-year-old female who sustained a compression fracture of the first lumbar
      vertebra (L1) in a motor vehicle accident. The fracture was treated by
      kyphoplasty using PMMA cement. Three weeks after hospital discharge the patient
      was presented with increasing back pain. In imaging, dislocation of the PMMA
      cement could be shown combined with a total collapse of the L1 vertebra. The
      resulting significant kyphosis was first reduced by dorsal transpedicular (Th12
      L2) internal fixation and stabilized by an anterior cage after total removal of
      the cement plomb and some remaining bone of the L1 vertebra. Bacterial as well as
      histological examination of the cement and bone led to the diagnosis of aseptic
      osteonecrosis. Different underlying events could be discussed. We think it most
      likely that the osteoporotic bone was unable to interface sufficiently with the
      PMMA cement and, therefore, disintegrated under loading. Furthermore, the volume
      of injected cement could have significantly compromised the blood supply within
      the bone.

PMID- 19089466
TI  - Efficacy and safety of posteromedial translation for correction of thoracic
      curves in adolescent idiopathic scoliosis using a new connection to the spine:
      the Universal Clamp.
AB  - Correction of adolescent idiopathic scoliosis (AIS) has been reported with
      various systems. All-screw constructs are currently the most popular, but they
      have been associated with a significant decrease in thoracic kyphosis, with a
      potential risk of junctional kyphosis, not observed with hybrid constructs in the
      literature. In addition, it is important to weigh potential advantages of pedicle
      screw fixation against risks specific to its use. Because hybrid constructs are
      associated with a lower risk of complications and better sagittal correction than
      all-screw constructs, at present we use lumbar pedicle screws combined with a new
      sublaminar connection to the spine (Universal Clamps) at thoracic levels. The
      purpose of this study was to determine the efficacy and safety of the Universal
      Clamp (UC) posteromedial translation technique for correction of AIS. Seventy
      five consecutive patients underwent posterior spinal fusion and hybrid
      instrumentation for progressive AIS. Correction was performed at the thoracic
      level using posteromedial translation. At the lumbar level, correction was
      performed using in situ contouring and compression/distractions maneuvers. A
      minimum 2-year follow-up was required. Medical data and radiographs were
      prospectively analyzed and compared using a paired t test. The average age at
      surgery was 15 years and 4 months (+/-19 months). The average number of levels
      fused was 12+/-1.6. The mean follow-up was 30+/-5 months. The average
      preoperative Cobb angle of the major curve was 60 degrees+/-20 degrees. The
      immediate postoperative major curve correction averaged 66+/-13%. The average
      loss of correction of the major curve between the early postoperative assessment
      and latest follow-up was 3.5 degrees+/-1.4 degrees . The mean Cincinnati
      correction index was 1.7+/-0.8 postoperatively, and 1.57+/-1 at last follow up.
      The mean rotation of the apical vertebra was corrected from 23.3 degrees+/-9
      degrees preoperatively to 7.3 degrees+/-5 degrees at last follow up (69%
      improvement, P<0.0001). In the sagittal plane, the mean thoracic kyphosis
      improved from 23.8 degrees+/-14.2 degrees preoperatively to 32.3 degrees+/-7.3
      degrees at last follow up. For the 68 patients who had a normokyphotic or a
      hypokyphotic sagittal modifier, thoracic kyphosis increased from 20.5 degrees+/
      9.9 degrees to 31.8 degrees+/-7.4 degrees, corresponding to a mean kyphosis
      correction of 55% at last follow up. No intraoperative complication occurred and
      none of the patients developed proximal junctional kyphosis during the follow up.
      The principal limitation of the UC technique was the rate of proximal posterior
      prominence (14.6%), leading us to recommend the use of conventional claws at the
      upper extremity of the construct. The technique was safe, and reduced operative
      time, radiation exposure, and blood loss. While achieving correction of deformity
      in the coronal and axial planes equivalent to the best reported results of all
      screw or previous hybrid constructs, the UC hybrid technique appears to provide
      superior correction in the sagittal plane. The excellent outcome in all three
      planes was maintained at 2 year follow up.

PMID- 19089468
TI  - Accurate micro- and macro- gas phase basicities of hydroxyl-radical-modified
      pyrimidines estimated by advanced quantum chemistry methods.
AB  - The gas phase basicities (GPB) of 16 hydroxyl-radical-derived analogues of model
      pyrimidine nucleosides were analysed at B3LYP/aug-cc-pVDZ and G3MP2B3 levels of
      theory. All possible tautomeric equilibriums of neutral and protonated forms of
      pyrimidine analogues were taken into account. The oxidation of pyrimidines
      usually reduces the GPB values with respect to canonical values. The only
      exception was observed in the case of 5,6-dihydroxycytidine, which is more basic
      than model cytidine if both macro- and micro-scopic measures of basicities are
      used for comparison. In addition, 6-hydroxycytidine is characterised more by the
      basic character of the O2 atom compared to the more basic centre of cytidine,
      despite the fact that the GPB values of both these compounds are almost
      identical. Although the B3LYP/aug-cc-pVDZ approach seems to be an accurate and
      robust method for GPB estimation, the microscopic protonation properties are much
      more sensitive to this method since the difference in energy between some
      tautomers is often less than 1 kcal/mol with method-dependent succession. In such
      cases, G3MP2B3 is recommended.

PMID- 19089467
TI  - Smoking increases salivary arginase activity in patients with dental implants.
AB  - It is believed that an increased arginase activity may lead to less nitric oxide
      production, which consequently increases the susceptibility to bacterial
      infection. Considering the hypothesis that smoking may alter the arginase
      activity and that smoking is considered a risk factor to dental implant survival,
      the present study aimed at evaluating the effect of smoking on the salivary
      arginase activity of patients with dental implants. Salivary samples of 41
      subjects were collected: ten non-smoking and with no dental implants (group A),
      ten non-smoking subjects with dental implants (group B), ten smoking subjects
      with implants (group C), and 11 smoking subjects with no dental implants (group
      D). The levels of salivary arginase activity were determined by the measurement
      of L-ornithine and expressed as mIU/mg of protein. A significant increase in the
      salivary arginase activity was verified in groups C (64.26 +/- 16.95) and D
      (49.55 +/- 10.01) compared to groups A (10.04 +/- 1.95, p = 0.00001 and p =
      0.0110, groups C and D, respectively) and B (11.77 +/- 1.45, p = 0.00001 and p =
      0.0147, groups C and D, respectively). No significant difference was found
      between groups C and D (p = 0.32). Within the limits of the present study, it can
      be concluded that salivary arginase activity is increased in smoking subjects
      with dental implants in contrast to non-smoking subjects with dental implants,
      therefore suggesting a possible mechanism by which cigarette smoking may lead to
      implant failure. The analysis of salivary arginase activity may represent an
      important tool to prevent implant failure in the near future.

PMID- 19089469
TI  - A theoretical study on unusual intermolecular T-shaped X-H...pi interactions
      between the singlet state HB=BH and HF, HCl, HCN or H2C2.
AB  - The unusual T-shaped X-H...pi hydrogen bonds are found between the B=B double
      bond of the singlet state HB=BH and the acid hydrogen of HF, HCl, HCN and H2C2
      using MP2 and B3LYP methods at 6-311++G(2df,2p) and aug-cc-pVTZ levels. The
      binding energies follow the order of
      HB=BH...HF>HB=BH...HCl>HB=BH...HCN>HB=BH...H2C2. The hydrogen-bonded interactions
      in HB=BH...HX are found to be stronger than those in H2C=CH2...HX and OCB
      identical withBCO...HX. The analyses of natural bond orbital (NBO) and the
      electron density shifts reveal that the nature of the T-shaped X-H...pi hydrogen
      bonded interaction is that much of the lost density from the pi-orbital of B=B
      bond is shifted toward the hydrogen atom of the proton donor, leading to the
      electron density accumulation and the formation of the hydrogen bond. The atoms
      in molecules (AIM) theory have also been applied to characterize bond critical
      points and confirm that the B=B double bond can be a potential proton acceptor.

PMID- 19089470
TI  - Properties and applications of the average interparticle distance.
AB  - The first and second moment operators are used to define the origin invariant
      shape and size of a molecule or functional group, as well as expressions for the
      distance between two electrons and the distance between an electron and a
      nucleus. The measure of molecular size correlates quite well with an existing
      theoretical measure of molecular volume calculated from isodensity contours.
      Also, the measure of size is effective in predicting steric effects of
      substituents which have been measured experimentally. The electron-electron and
      electron-nuclear distances are related to components of the Hartree-Fock energy.
      The average distance between two-electrons can model the Coulomb energy quite
      well, especially in the case of localized molecular orbitals. The average
      distance between an electron and a nucleus is closely related to the electron
      nuclear attraction energy of a molecule.

PMID- 19089471
TI  - Density functional and Moller-Plesset studies of cyclobutanone[...]HF and
      [...]HCl complexes.
AB  - The molecular structure (hydrogen bonding, bond distances and angles), dipole
      moment and vibrational spectroscopic data [vibrational frequencies, IR and
      vibrational circular dichroism (VCD)] of cyclobutanonecdots, three dots,
      centeredHX (X = F, Cl) complexes were calculated using density functional theory
      (DFT) and second order Moller-Plesset perturbation theory (MP2) with basis sets
      ranging from 6-311G, 6-311G(**), 6-311 + + G(**). The theoretical results are
      discussed mainly in terms of comparisons with available experimental data. For
      geometric data, good agreement between theory and experiment is obtained for the
      MP2 and B3LYP levels with basis sets including diffuse functions. Surface
      potential energy calculations were carried out with scanning HCl and HF near the
      oxygen atom. The nonlinear hydrogen bonds of 1.81 A and 175 degrees for HCl and
      1.71 A and 161 degrees for HF were calculated. In these complexes the C=O and H-X
      bonds participating in the hydrogen bond are elongated, while others bonds are
      compressed. The calculated vibrational spectra were interpreted and the band
      assignments reported are in excellent agreement with experimental IR spectra. The
      C=O stretching vibrational frequencies of the complexes show red shifts with
      respect to cyclobutanone.

PMID- 19089472
TI  - Mitochondrial complex I deficiency in GDAP1-related autosomal dominant Charcot
      Marie-Tooth disease (CMT2K).
AB  - Mutations in GDAP1, an outer mitochondrial membrane protein responsible for
      recessive Charcot-Marie-Tooth disease (CMT4A), have also been associated with
      CMT2K, a dominant form of the disease. The three CMT2K patients we studied
      carried a novel dominant GDAP1 mutation, C240Y (c.719G > A). Mitochondrial
      respiratory chain complex I activity in fibroblasts from CMT2K patients was 40%
      lower than in controls, whereas the tubular mitochondria were 33% larger in
      diameter and the mitochondrial mass was 20% greater. Thus, besides the regulatory
      role GDAP1 plays in mitochondrial network dynamics, it may also be involved in
      energy production and in the control of mitochondrial volume.

PMID- 19089473
TI  - Humoral immunodeficiency in congenital insensitivity to pain with anhidrosis.
AB  - Congenital insensitivity to pain with anhidrosis (CIPA) is an autosomal recessive
      disorder caused by mutations in the neurotrophic tyrosine receptor kinase 1
      (NTRK1) gene, which encodes the receptor for nerve growth factor. We report the
      clinical course of a 7-year-old girl with CIPA and proven NTRK1 mutation. In
      addition to recurrent dislocation of the left hip joint and avascular necrosis of
      the left talus, the patient also presented with recurrent infections secondary to
      hypogammaglobulinemia, a feature not previously known to be associated with CIPA.
      The patient was treated with regular administration of intravenous
      immunoglobulins. Conservative treatment of the recurrent left hip dislocation by
      cast immobilization and bracing was implemented to stabilize the joint. The
      implication of the immune system of the reported patient broadens the clinical
      phenotype associated with NTRK1 mutations.

PMID- 19089474
TI  - Familial risks for amyotrophic lateral sclerosis and autoimmune diseases.
AB  - Population-level familial risks are not available for amyotrophic lateral
      sclerosis (ALS), and a few studies have analyzed familial association of ALS with
      other diseases. We used the Swedish Multigeneration Register to identify family
      members and link them to the Hospital Discharge Register to calculate
      standardized incidence ratios (SIRs) for familial association in ALS and 33
      autoimmune diseases. Among 4,970 ALS patients, familial SIR for offspring of
      affected parents was 4.71, for singleton siblings, it was 29.83, and for members
      of multiplex families, it was 1,100; 1.1% of the offspring had an affected
      parent, and 2.2% an affected sibling. The high risks among siblings without
      affected parents may suggest recessive inheritance. The SIR for spouse
      correlation for ALS was 2.35 which may imply the influence of yet unknown
      environmental factors in ALS susceptibility. ALS associated with Behcet disease,
      multiple sclerosis, ulcerative colitis, and Wegener granulomatosis; however,
      chance associations cannot be excluded. In this first population level family
      study on ALS and 33 autoimmune and related conditions, we found high familial
      risks depending on the proband. These findings should guide future genomic
      studies. The high spouse correlation will be a challenge to environmental
      epidemiology of ALS.

PMID- 19089475
TI  - Grimontia hollisae, a potential agent of gastroenteritis and bacteraemia in the
      Mediterranean area.
AB  - Vibrio hollisae was first described in 1982 as an agent of diarrhoea and was
      reclassified in 2003 into a novel genus as Grimontia hollisae. We report the
      first case of G. hollisae bacteraemia in the Mediterranean area, in an 81-year
      old man with a severe gastroenteritis and hepatitis following the consumption of
      raw oysters. The incidence of this micro-organism as an agent of gastroenteritis
      may be underestimated because it may not be detected using routine culture
      conditions.

PMID- 19089476
TI  - Isolation of Corynebacterium ureicelerivorans from normally sterile sites in
      humans.
AB  - Fifteen Corynebacterium ureicelerivorans isolates were recovered in pure culture
      from six patients during a five-year period. Five patients had bacteremia and the
      other was an infection of ascitic fluid. The API Coryne numerical profile
      obtained corresponds to the profile for C. bovis, while Biolog GP2 identified
      four out of the six isolates as C. jeikeium. The organisms were molecular
      identified by 16S rDNA and rpoB. The present report also includes information on
      new phenotypic tests and, for the first time, antimicrobial susceptibility data
      of C. ureicelerivorans and their rpoB sequences. All macrolide-resistant isolates
      presented a constitutive MLS phenotype. This organism must be differentiated from
      other slow-growing, lipophilic, and urea-splitting corynebacteria.

PMID- 19089478
TI  - Novel macroarray-based method of Corynebacterium diphtheriae genotyping:
      evaluation in a field study in Belarus.
AB  - In this study, we evaluated a novel macroarray-based spoligotyping method for
      Corynebacterium diphtheriae strain typing. A total of 20 C. diphtheriae biotype
      gravis toxigenic isolates collected in Belarus from suspected foci of diphtheria
      infection (diphtheria cases, carriers, or contacts) were subjected to DNA
      fingerprinting. All strains had an identical ribotyping profile that was
      identified as ribotype 'Rossija' by comparison with the international ribotype
      database at the Institut Pasteur of Paris. A spoligotyping method based on
      simultaneous reverse-hybridization analysis of two CRISPR (clustered, regularly
      interspaced short palindromic repeats) loci differentiated these strains into
      three spoligotypes. Comparison of the spoligotyping results with the
      epidemiological linkage network helped us to resolve suspected links in the
      chains of transmission. To conclude, the C. diphtheriae spoligotyping method
      demonstrated its utility in the field study, in particular, underlining the
      importance of the use of both CRISPR loci. The generated discrete data can be
      presented in digital binary format and be easily exchanged between laboratories
      and stored in local and global databases.

PMID- 19089479
TI  - Internal hernia complications of gastric bypass surgery in the acute setting:
      spectrum of imaging findings.
AB  - Bariatric surgery is increasingly becoming an option for the treatment of morbid
      obesity. Patients who have undergone gastric bypass surgery have varied post
      surgical complications which present acutely in the emergency medical setting,
      particularly internal hernias. It may be difficult to identify an internal hernia
      in the absence of intestinal obstruction. This article will review the various
      types of imaging presentations to highlight the complexity of making a
      radiographic diagnosis. Recognition of internal hernia as the cause of
      intermittent or acute abdominal pain symptoms in these patients in the emergency
      setting can prompt immediate surgical intervention, thus avoiding life
      threatening outcomes.

PMID- 19089477
TI  - Influence of Helicobacter pylori infection on the expression of MLH1 and MGMT in
      patients with chronic gastritis and gastric cancer.
AB  - The aim of the present study was to evaluate the influence of Helicobacter pylori
      on MLH1 and MGMT mRNA levels in patients with chronic gastritis and gastric
      cancer. The study included 217 patients, of which 26 were uninfected, 127 had
      chronic gastritis and were H. pylori-positive, and 64 had gastric cancer.
      Bacterial genotypes were evaluated by polymerase chain reaction (PCR), and the
      expression levels of MLH1 and MGMT were determined by quantitative real-time PCR
      and immunohistochemistry. There was an association between infection with cagA,
      vacA s1m1 strains and gastric cancer development. When the gastric epithelium and
      associated inflammation were examined for expression of MLH1 and MGMT, an overall
      increase in expression was observed. On the other hand, these levels decrease
      significantly among gastric cancer patients. The loss of MLH1 and MGMT expression
      in gastric cancer patients suggests that it is not an early event in H. pylori
      associated gastric carcinogenesis.

PMID- 19089480
TI  - Nano-meter-sized domain formation in lipid membranes observed by small angle
      neutron scattering.
AB  - Using a contrast matching technique of small angle neutron scattering (SANS), we
      have investigated a phase separation to liquid-disordered and liquid-ordered
      phases on ternary small unilamellar vesicles (SUVs) composed of deuterated
      saturated, hydrogenated-unsaturated phosphatidylcholine lipids and cholesterol,
      where the equilibrium size of these domains is constrained to less than 10nm by
      the system size. Below a miscibility temperature, we observed characteristic
      scattering profiles with a maximum, indicating the formation of nano-meter-sized
      domains on the SUVs. The observed profiles can be described by a multi-domain
      model rather than a mono-domain model. The nano-meter-sized domain is agitated by
      thermal fluctuations and eventually ruptured, which may result in the multi
      domain state. The kinetically trapped nano-meter-sized domains grow to a mono
      domain state by decreasing temperature. Furthermore, between the miscibility and
      disorder-order transition temperature of saturated lipid, the integrated SANS
      intensity increased slightly, indicating the formation of nano-meter-sized
      heterogeneity prior to the domain nucleation.

PMID- 19089481
TI  - Activation of T-lymphocytes by LDL-cholesterol.
AB  - Native LDL-cholesterol can be mechanically stressed by strong vortexing.
      According to one hypothesis, mechanical shear stress within the vessel can lead
      to an aggregation of LDL-cholesterol and subsequently to activation of CD4 and
      CD8 T-lymphocytes. The goal of this study was to determine the proportion of
      activated CD4 and CD8 T-lymphocytes that is induced by adding unstressed and
      mechanically stressed LDL-cholesterol to whole blood samples. Whole blood was
      taken from 12 healthy subjects. All probands fasted for at least 12 h before
      blood withdrawal. In each case, 1 ml of whole blood from each subject was
      incubated for 16 h at 32 degrees C (89.3 degrees F) with concanavalin A (A),
      without additive (B), with mechanically stressed LDL-cholesterol (C) or with
      native LDL-cholesterol (D). Subsequently, the samples were measured by four-color
      flow cytometry. CD3, CD4, CD8, and CD69 were measured as activity markers. CD69
      was plotted against CD4 and CD8, and the proportions of activated CD4 and CD8 T
      lymphocytes were determined. Native and vortexed LDL-cholesterol elicited
      significantly different types of T-cell activation. While native LDL activated
      CD4 T-cells to only a small extent, mechanically stressed (vortexed) LDL potently
      activated CD8 T-cells. Purely mechanically-induced changes in LDL-cholesterol may
      be one mechanism that contributes to the activation of CD8 cells and, as a
      consequence, the emergence of arteriosclerosis.

PMID- 19089482
TI  - Preparative separation of cis- and trans-isomers of unsaturated fatty acid methyl
      esters contained in edible oils by reversed-phase high-performance liquid
      chromatography.
AB  - In order to measure exactly the trans-fatty acids content in food materials, a
      preparative group separation of cis- and trans-isomers of unsaturated fatty acid
      methyl esters (FAMEs) was achieved by an isocratic reversed-phase HPLC (RP-HPLC)
      method. The trans-isomers of 16:1, 18:1, 18:2, 18:3, 20:1 and 22:1 FAMEs were
      readily separated from the corresponding cis-isomers by a COSMOSIL Cholester C18
      column (4.6 mm I.D. x 250 mm, Nacalai Tesque) or a TSKgel ODS-100Z column (4.6 mm
      I.D. x 250 mm, TOSOH), using acetonitrile as the mobile phase. This method was
      applied for determining the trans-18:1 fatty acid content in partially
      hydrogenated rapeseed oil. The methyl esters of cis- and trans-18:1 isomers of
      the oil were collected as two separate fractions by the developed RP-HPLC method.
      Each fraction was analyzed by gas chromatography (GC) for both qualitative and
      quantitative information on its positional isomers. By a combination of RP-HPLC
      and GC methods, a nearly complete separation of cis- and trans-18:1 positional
      isomers was achieved and the trans-18:1 fatty acid content was able to be
      evaluated more precisely than is possible by the direct GC method. The
      reproducibility of cis- and trans-18:1 isomers fractionated by the RP-HPLC method
      was better than 98%. These results suggested that the preparative RP-HPLC method
      developed in this study could be a powerful tool for trans-fatty acid analysis in
      edible oils and food products as an alternative to silver-ion chromatography.

PMID- 19089483
TI  - [Nobel Prize in Medicine 2008: The discovery of HIV and cancer-causing human
      papillomaviruses].

PMID- 19089486
TI  - Oxidative stress in fibromyalgia and its relationship to symptoms.
AB  - Oxidative stress is thought to play a role in the pathogenesis of fibromyalgia.
      We examined the hypothesis that oxidative stress was increased in patients with
      fibromyalgia and related to the severity of symptoms. Urinary F(2)-isoprostane
      excretion was measured in 48 patients with fibromyalgia and compared to those of
      96 control subjects. In patients, we examined the association between oxidative
      stress and symptoms. Patients with fibromyalgia were significantly more
      symptomatic than control subjects, but urinary F(2)-isoprostane excretion did not
      differ significantly (2.3+/-1.9 vs. 2.8+/-2.2 ng/mg creatinine, p=0.16). In
      patients with fibromyalgia, F(2)-isoprostane excretion was associated with
      fatigue visual analog scale (rho=0.30, p=0.04) but not with pain, quality of
      life, functional capacity, depression, number of tender points, or overall impact
      of fibromyalgia. Oxidative stress is not increased in patients with fibromyalgia,
      but as was previously found in patients with systemic lupus erythematosus,
      oxidative stress was associated with fatigue.

PMID- 19089487
TI  - The coexistence of ankylosing spondylitis and diffuse idiopathic skeletal
      hyperostosis--a postmortem diagnosis.
AB  - A 72-year-old male was diagnosed as having ankylosing spondylitis, mainly
      according to radiological findings, confirmed as HLA-B27-negative. Postmortem
      examination of the skeleton raised doubts on the initial diagnosis, since spinal
      findings pointed out also to diffuse idiopathic skeletal hyperostosis. The
      authors discuss the differential diagnosis and enhance the postmortem findings
      which allowed the diagnosis of the two clinical entities in the same patient.

PMID- 19089489
TI  - The effect of mild whole-body hyperthermia on systemic levels of TNF-alpha, IL
      1beta, and IL-6 in patients with ankylosing spondylitis.
AB  - Serial mild whole-body hyperthermia is a widely used balneotherapy modality for
      clinically inactive ankylosing spondylitis (AS) in rehabilitative medicine. Thus
      far, the mechanisms of its favorable influence on the symptoms of AS are not
      completely understood. We therefore analyzed the effect of mild whole-body
      hyperthermia on the systemic levels of pivotal proinflammatory cytokines. Twelve
      male subjects with AS and 12 healthy control subjects received nine cycles of
      whole-body hyperthermia (target body core temperature, 38.5 degrees C; duration,
      50 min). Serum samples were taken at the beginning of the last cycle and at 1, 6,
      and 24 h for measurement of tumor necrosis factor alpha, interleukin 1beta and
      interleukin 6. Significant differences of cytokine levels were found between both
      groups. In AS patients, hyperthermia caused a significant reduction of all
      cytokines by 40-50%. Thus, serial mild whole-body hyperthermia in AS results in
      heat-induced changes of the proinflammatory cytokine network.

PMID- 19089488
TI  - Cost-effectiveness modeling of abatacept versus other biologic agents in DMARDS
      and anti-TNF inadequate responders for the management of moderate to severe
      rheumatoid arthritis.
AB  - To assess the cost-effectiveness of abatacept compared to different biologic
      treatment strategies for moderate to severe rheumatoid arthritis based on current
      medical practices in Canada. A model was constructed to assess the cost
      effectiveness of various biologic treatments over a 2-year time horizon, using
      two effectiveness endpoints: "low disease activity state" (LDAS) and "remission".
      Abatacept, as first biologic agent after an inadequate response to DMARDs,
      provides greater treatment success rate for achieving LDAS (29.4% versus 15.6%)
      and remission (14.8% versus 5.2%), and appears significantly more cost-effective
      compared to the sequential use of anti-TNF agents (p<0.001). Abatacept, as second
      biologic agent after an inadequate response to one anti-TNF agent, provides
      greater treatment success rate for achieving LDAS (17.1% versus 10.2%) and
      remission (7.4% versus 3.9%) and appears significantly more cost-effective
      compared to the sequential use of anti-TNF agents (p<0.001). Abatacept is a cost
      effective strategy in patients with an inadequate response to DMARDs or to one
      anti-TNF agent.

PMID- 19089490
TI  - Comparison of polyp distance on CT colonography between supine and prone scans
      using an automated path-distance measurement tool: correlation with colonoscopy.
AB  - OBJECTIVE: To investigate the proximity of polyp distance on CT colonography
      (CTC) between supine and prone scans using an automated path-distance measurement
      tool and to correlate the path distance of polyps with that of colonoscopy.
      METHODS: Of 196 polyps in 85 patients, 98 polyps (25 <6 mm, 42 6-9.9 mm, 31 > or
      =10 mm) detected on supine and prone positions in 72 patients, were included. The
      location of each polyp, which was expressed as the distance from the tip of the
      rectum, was measured using an automated path-distance measurement tool and was
      compared between the two positions. The effect of colonic collapse on the
      proximity of polyp distance between the two scans was analyzed. The automated
      path distance of 50 polyps in the rectosigmoid colon was correlated with that of
      colonoscopy. RESULTS: Mean difference of the automated path distances of polyps
      between the two positions was 2.6 cm and was not significantly different between
      the two positions (P > 0.05). Correlation coefficient (gamma) between the two
      positions was 0.9977. The difference of the distance of polyps between the groups
      with or without colonic collapse was not significant (P > 0.05). Automated path
      distance of 50 polyps in the sigmoid colon or rectum was generally well
      correlated with that on colonoscopy (gamma = 0.8005, P < 0.0001) and the mean
      difference was 5.1 cm. The mean difference increased as the polyp distance from
      the point of reference became further located, and reached significance when the
      distance was further than 30 cm from the tip of the rectum (P = 0.002).
      CONCLUSION: Automated path distance of polyps matches closely between the two
      positions and is not influenced by the presence of collapsed segments. Polyps
      located 30 cm or further from the tip of the rectum on CTC do not match closely
      with that on colonoscopy.

PMID- 19089491
TI  - Percutaneous renal tumor ablation.
AB  - Recent increase in utilization of cross-sectional imaging has resulted in
      increased detection of early renal cancer. Percutaneous ablation is a relatively
      new technique for the treatment of renal cancer. This article provides an
      overview of clinical indications, technique, and results of percutaneous ablation
      of renal cancer.

PMID- 19089492
TI  - Use of tissue sealants in face-lifts: a metaanalysis.
AB  - BACKGROUND: This review sought to determine the efficacy of tissue sealants such
      as fibrin tissue adhesives and platelet-rich plasma in reducing postoperative
      drainage, ecchymosis, and edema after face-lift surgery. METHODS: The electronic
      databases MEDLINE (1966-May 2007) and EMBASE (1974-May 2007) and the Cochrane
      Central Register of Controlled Trials (CENTRAL) were searched for human studies,
      randomized controlled trials, controlled clinical trials, metaanalyses, and
      reviews of randomized controlled trials using the key words "fibrin tissue
      adhesive," "tissue sealant," "platelet-rich plasma," "face-lift,"
      "rhytidoplasty," "rhytidectomy," and "facial plastic surgery." The search yielded
      10 articles, only 3 of which met our inclusion criteria. The three studies were
      within-patient comparisons (patients acted as their own controls). RESULTS:
      Although not statistically significant, the pooled results showed a strong trend
      toward reduction in postoperative drainage at 24 h and ecchymosis with the use of
      tissue sealants compared with the control arm of the study. No difference in
      outcomes was observed between the tissue sealant and control arms of the study in
      terms of postoperative edema measurement. CONCLUSION: There was no statistically
      significant benefit from the use of tissue sealants in face-lift surgery.
      However, tissue sealants may be useful for patients at a high risk for hematoma
      and ecchymosis formation.

PMID- 19089493
TI  - Photographic facial soft tissue analysis of healthy Turkish young adults:
      anthropometric measurements.
AB  - BACKGROUND: The purpose of this study was to establish facial soft tissue norms
      for Turkish young adults. METHODS: Anthropometric measurements of the facial soft
      tissue were taken from 281 female and 149 male Turkish adults aged between 18 and
      24 years. The soft tissue facial profiles were digitally analyzed using linear
      (17 vertical and 10 horizontal) measurements made with standardized photographic
      records, taken in a natural head position, to determine the average soft tissue
      facial profile for males and females. RESULTS: A statistically significant
      difference was found between males and females in 20 of 27 measurements taken (p
      < 0.001). The most prominent differences between the sexes were observed in the
      measurements taken from the face region. Results were compared with other ethnic
      groups.

PMID- 19089494
TI  - Temporary closure of the open abdomen: a systematic review on delayed primary
      fascial closure in patients with an open abdomen.
AB  - BACKGROUND: This study was designed to systematically review the literature to
      assess which temporary abdominal closure (TAC) technique is associated with the
      highest delayed primary fascial closure (FC) rate. In some cases of abdominal
      trauma or infection, edema or packing precludes fascial closure after laparotomy.
      This "open abdomen" must then be temporarily closed. However, the FC rate varies
      between techniques. METHODS: The Cochrane Register of Controlled Trials, MEDLINE,
      and EMBASE databases were searched until December 2007. References were checked
      for additional studies. Search criteria included (synonyms of) "open abdomen,"
      "fascial closure," "vacuum," "reapproximation," and "ventral hernia." Open
      abdomen was defined as "the inability to close the abdominal fascia after
      laparotomy." Two reviewers independently extracted data from original articles by
      using a predefined checklist. RESULTS: The search identified 154 abstracts of
      which 96 were considered relevant. No comparative studies were identified. After
      reading them, 51 articles, including 57 case series were included. The techniques
      described were vacuum-assisted closure (VAC; 8 series), vacuum pack (15 series),
      artificial burr (4 series), Mesh/sheet (16 series), zipper (7 series), silo (3
      series), skin closure (2 series), dynamic retention sutures (DRS), and loose
      packing (1 series each). The highest FC rates were seen in the artificial burr
      (90%), DRS (85%), and VAC (60%). The lowest mortality rates were seen in the
      artificial burr (17%), VAC (18%), and DRS (23%). CONCLUSIONS: These results
      suggest that the artificial burr and the VAC are associated with the highest FC
      rates and the lowest mortality rates.

PMID- 19089495
TI  - Responses to diotic, dichotic, and alternating phase harmonic stimuli in the
      inferior colliculus of guinea pigs.
AB  - Humans perceive a harmonic series as a single auditory object with a pitch
      equivalent to the fundamental frequency (F0) of the series. When harmonics are
      presented to alternate ears, the repetition rate of the waveform at each ear
      doubles. If the harmonics are resolved, then the pitch perceived is still
      equivalent to F0, suggesting the stimulus is binaurally integrated before pitch
      is processed. However, unresolved harmonics give rise to the doubling of pitch
      which would be expected from monaural processing (Bernstein and Oxenham, J.
      Acoust. Soc. Am., 113:3323-3334, 2003). We used similar stimuli to record
      responses of multi-unit clusters in the central nucleus of the inferior
      colliculus (IC) of anesthetized guinea pigs (urethane supplemented by
      fentanyl/fluanisone) to determine the nature of the representation of harmonic
      stimuli and to what extent there was binaural integration. We examined both the
      temporal and rate-tuning of IC clusters and found no evidence for binaural
      integration. Stimuli comprised all harmonics below 10 kHz with fundamental
      frequencies (F0) from 50 to 400 Hz in half-octave steps. In diotic conditions,
      all the harmonics were presented to both ears. In dichotic conditions, odd
      harmonics were presented to one ear and even harmonics to the other. Neural
      characteristic frequencies (CF, n = 85) were from 0.2 to 14.7 kHz; 29 had CFs
      below 1 kHz. The majority of clusters responded predominantly to the
      contralateral ear, with the dominance of the contralateral ear increasing with
      CF. With diotic stimuli, over half of the clusters (58%) had peaked firing rate
      vs. F0 functions. The most common peak F0 was 141 Hz. Almost all (98%) clusters
      phase locked diotically to an F0 of 50 Hz, and approximately 40% of clusters
      still phase locked significantly (Rayleigh coefficient >13.8) at the highest F0
      tested (400 Hz). These results are consistent with the previous reports of
      responses to amplitude-modulated stimuli. Clusters phase locked significantly at
      a frequency equal to F0 for contralateral and diotic stimuli but at 2F0 for
      dichotic stimuli. We interpret these data as responses following the envelope
      periodicity in monaural channels rather than as a binaurally integrated
      representation.

PMID- 19089496
TI  - Sciatic nerve injury associated with acetabular fractures.
AB  - Sciatic nerve injuries associated with acetabular fractures may be a result of
      the initial trauma or injury at the time of surgical reconstruction. Patients may
      present with a broad range of symptoms ranging from radiculopathy to foot drop.
      There are several posttraumatic, perioperative, and postoperative causes for
      sciatic nerve palsy including fracture-dislocation of the hip joint, excessive
      tension or inappropriate placement of retractors, instrument- or implant-related
      complications, heterotopic ossification, hematoma, and scarring. Natural history
      studies suggest that nerve recovery depends on several factors. Prevention
      requires attention to intraoperative limb positioning, retractor placement, and
      instrumentation. Somatosensory evoked potentials and spontaneous electromyography
      may help minimize iatrogenic nerve injury. Heterotopic ossification prophylaxis
      can help reduce delayed sciatic nerve entrapment. Reports on sciatic nerve
      decompression are not uniformly consistent but appear to have better outcomes for
      sensory than motor neuropathy.

PMID- 19089497
TI  - Flexor tenorrhaphy tensile strength: reduction by cyclic loading: in vitro and ex
      vivo porcine study.
AB  - The integrity of the repair is critical to maintain coaptation of the severed
      flexor tendon end until healing has advanced sufficiently. In our hospital, we
      use a modified Savage repair (four-strand Adelaide technique) using 3-0 Ethibond
      (Ethicon, Somerville, NJ, USA) for acute flexor tenorrhaphy and an active
      postrepair mobilization protocol. To explain the apparent differences between the
      theoretical and actual repair strength of a multistrand repair in a single
      tension test and the reduced strength of a repair subjected to cyclic loading, we
      compared single and cyclical tensile loading with different suture in vitro
      configurations of 3-0 Ethibond (Ethicon, Somerville, NJ, USA; one, two, and four
      strands) and an ex vivo four-strand repair of freshly divided porcine tendon to
      calculate the ultimate tensile strength (UTS). Mechanical testing was repeated 15
      times with both single tensile and cyclical loading for each suture configuration
      and porcine repair. In the in vitro model, the presence of a knot in a single
      strand reduced the UTS by 50%. The stiffness of a knotted strand was
      substantially less than the unknotted strand but became identical after cyclical
      loading. There was no statistical significance of the UTS between single and
      cyclical loading with different numbers of strands in this model. In the ex vivo
      four-strand porcine repair model, there was a significant reduction in UTS with
      cyclical loading, which equated to the number of strands times the strength of
      the knotted strand. This discrepancy can be explained by the change in stiffness
      of the knotted strand after cyclical loading and has important implications for
      previous studies of suture tendon repair using single tensile loading where the
      UTS may have been overestimated. We believe that cyclical loading is more
      representative of physiological loading after acute flexor tendon repair and
      should be the testing model of choice in suture tenorrhaphy studies.

PMID- 19089498
TI  - Cardiovascular risk factors and knowledge of symptoms among Vietnamese Americans.
AB  - BACKGROUND: There are few population-based studies of cardiovascular risk
      factors, knowledge, and related behaviors among Vietnamese Americans. OBJECTIVE:
      To describe cardiovascular risk factors, knowledge, and related behaviors among
      Vietnamese Americans and compare the results to non-Hispanic whites. DESIGN:
      Comparison of data from two population-based, cross-sectional telephone surveys.
      PARTICIPANTS: Vietnamese Americans in Santa Clara County, California, and non
      Hispanic whites in California, aged 18 and older. MEASUREMENTS: Survey measures
      included sociodemographics, diagnoses, body mass index, fruit and vegetable
      intake, exercise, and tobacco use. Knowledge of symptoms of heart attack and
      stroke was collected for Vietnamese Americans. MAIN RESULTS: Compared to non
      Hispanic whites (n = 19,324), Vietnamese Americans (n = 4,254) reported lower
      prevalences of obesity, diabetes mellitus, coronary heart disease, and
      hypertension, and similar prevalences of stroke and hypercholesterolemia. Fewer
      Vietnamese Americans consumed fruits and vegetables five or more times daily
      (27.8% vs 16.3%, p < 0.05), and more reported no moderate or vigorous physical
      activity (12.1% vs 40.1%, p < 0.05). More Vietnamese men than non-Hispanic White
      men were current smokers (29.8% vs 19.0%, p < 0.05). Vietnamese Americans who
      spoke Vietnamese were more likely than those who spoke English to eat fruits and
      vegetables less frequently, engage in no moderate or vigorous physical activity,
      and, among men, be current smokers. Only 59% of Vietnamese Americans knew that
      chest pain was a symptom of heart attack. CONCLUSIONS: There are significant
      disparities in risk factors and knowledge of symptoms of cardiovascular diseases
      among Vietnamese Americans. Culturally appropriate studies and interventions are
      needed to understand and to reduce these disparities.

PMID- 19089499
TI  - Incorporating disparity reduction into pay-for-performance.

PMID- 19089500
TI  - Integrating buprenorphine treatment into office-based practice: a qualitative
      study.
AB  - BACKGROUND: Despite the availability and demonstrated effectiveness of office
      based buprenorphine maintenance treatment (BMT), the systematic examination of
      physicians' attitudes towards this new medical practice has been largely
      neglected. OBJECTIVE: To identify facilitators and barriers to the potential or
      actual implementation of BMT by office-based medical providers. DESIGN:
      Qualitative study using individual and group semi-structured interviews.
      PARTICIPANTS: Twenty-three practicing office-based physicians in New England.
      APPROACH: Interviews were audiotaped, transcribed, and entered into a qualitative
      software program. The transcripts were thematically coded using the constant
      comparative method by a multidisciplinary team. RESULTS: Eighty percent of the
      physicians were white; 55% were women. The mean number of years since graduating
      medical school was 14 (SD = 10). The primary areas of clinical specialization
      were internal medicine (50%), infectious disease (20%), and addiction medicine
      (15%). Physicians identified physician, patient, and logistical factors that
      would either facilitate or serve as a barrier to their integration of BMT into
      clinical practice. Physician facilitators included promoting continuity of
      patient care, positive perceptions of BMT, and viewing BMT as a positive
      alternative to methadone maintenance. Physician barriers included competing
      activities, lack of interest, and lack of expertise in addiction treatment.
      Physicians' perceptions of patient-related barriers included concerns about
      confidentiality and cost, and low motivation for treatment. Perceived logistical
      barriers included lack of remuneration for BMT, limited ancillary support for
      physicians, not enough time, and a perceived low prevalence of opioid dependence
      in physicians' practices. CONCLUSIONS: Addressing physicians' perceptions of
      facilitators and barriers to BMT is crucial to supporting the further expansion
      of BMT into primary care and office-based practices.

PMID- 19089501
TI  - Perceived helpfulness of physicians' communication behavior and breast cancer
      patients' level of trust over time.
AB  - OBJECTIVE: We evaluated the association between physicians' communication
      behavior and breast cancer patients' trust in their physicians. DESIGN:
      Longitudinal survey conducted at baseline, 2-month, and 5-month follow-up during
      first year of diagnosis. PARTICIPANTS: Newly diagnosed breast cancer patients (N
      = 246). MEASUREMENTS: We collected data on patient perceptions of the helpfulness
      of informational, emotional, and decision-making support provided by physicians
      and patients' trust. Linear regression models evaluated the association of
      concurrent and prior levels of physician support with patients' trust. RESULTS:
      At baseline, patients who received helpful informational, emotional, and decision
      making support from physicians reported greater trust (p < 0.05, p < 0.001, and p
      < 0.01, respectively). At the 2-month assessment, baseline informational support
      and informational and emotional support at 2-months were associated with greater
      trust (p < 0.05, p < 0.01, and p < 0.05, respectively). At the 5-month
      assessment, only helpful emotional support from physicians at 5 months was
      associated with greater trust (p < 0.01). Interestingly, while perceived
      helpfulness of all three types of physician support decreased significantly over
      time, patient trust remained high and unchanged. CONCLUSIONS: Findings suggest
      that while informational and decision-making support may be more important to
      patient trust early in the course of treatment, emotional support from physicians
      may be important to maintain trust throughout the initial year of diagnosis.

PMID- 19089502
TI  - Gabapentin versus tricyclic antidepressants for diabetic neuropathy and post
      herpetic neuralgia: discrepancies between direct and indirect meta-analyses of
      randomized controlled trials.
AB  - BACKGROUND: Previous systematic reviews concluded that tricyclics antidepressants
      are superior to gabapentin for neuropathic pain, but were based on indirect
      comparisons from placebo-controlled trials. PURPOSE: To evaluate gabapentin
      versus tricyclic antidepressants for diabetic neuropathy and post-herpetic
      neuralgia, using direct and indirect comparisons. DATA SOURCES: MEDLINE (1966 to
      March Week 4 2008), the Cochrane central register of controlled trials (1st
      quarter 2008), and reference lists. STUDY SELECTION: We selected randomized
      trials directly comparing gabapentin versus tricyclic antidepressants or
      comparing either of these medications versus placebo. DATA EXTRACTION: Studies
      were reviewed, abstracted, and quality-rated by two independent investigators
      using predefined criteria. DATA SYNTHESIS: We performed a meta-analysis of head
      to-head trials using a random effects model and compared the results to an
      adjusted indirect analysis of placebo-controlled trials. RESULTS: In three head
      to-head trials, there was no difference between gabapentin and tricyclic
      antidepressants for achieving pain relief (RR 0.99, 95% CI 0.76 to 1.29). In
      adjusted indirect analyses, gabapentin was worse than tricyclic antidepressants
      for achieving pain relief (RR = 0.41, 95% CI 0.23 to 0.74). The discrepancy
      between direct and indirect analyses was statistically significant (p = 0.008).
      Placebo-controlled tricyclic trials were conducted earlier than the gabapentin
      trials, reported lower placebo response rates, had more methodological
      shortcomings, and were associated with funnel plot asymmetry. CONCLUSIONS: Though
      direct evidence is limited, we found no difference in likelihood of achieving
      pain relief between gabapentin and tricyclic antidepressants for diabetic
      neuropathy and post-herpetic neuralgia. Indirect analyses that combine data from
      sets of trials conducted in different eras can be unreliable.

PMID- 19089503
TI  - Getting by: underuse of interpreters by resident physicians.
AB  - BACKGROUND: Language barriers complicate physician-patient communication and
      adversely affect healthcare quality. Research suggests that physicians underuse
      interpreters despite evidence of benefits and even when services are readily
      available. The reasons underlying the underuse of interpreters are poorly
      understood. OBJECTIVE: To understand the decision-making process of resident
      physicians when communicating with patients with limited English proficiency
      (LEP). DESIGN: Qualitative study using in-depth interviews. PARTICIPANTS:
      Internal medicine resident physicians (n = 20) from two urban teaching hospitals
      with excellent interpreter services. APPROACH: An interview guide was used to
      explore decision making about interpreter use. RESULTS: Four recurrent themes
      emerged: 1) Resident physicians recognized that they underused professional
      interpreters, and described this phenomenon as "getting by;" 2) Resident
      physicians made decisions about interpreter use by weighing the perceived value
      of communication in clinical decision making against their own time constraints;
      3) The decision to call an interpreter could be preempted by the convenience of
      using family members or the resident physician's use of his/her own second
      language skills; 4) Resident physicians normalized the underuse of professional
      interpreters, despite recognition that patients with LEP are not receiving equal
      care. CONCLUSIONS: Although previous research has identified time constraints and
      lack of availability of interpreters as reasons for their underuse, our data
      suggest that the reasons are far more complex. Residents at the study
      institutions with interpreters readily available found it easier to "get by"
      without an interpreter, despite misgivings about negative implications for
      quality of care. Findings suggest that increasing interpreter use will require
      interventions targeted at both individual physicians and the practice
      environment.

PMID- 19089507
TI  - "What is found there": qualitative analysis of physician-nurse collaboration
      stories.
AB  - BACKGROUND: Effective physician-nurse collaboration is an important, but
      incompletely understood determinant of patient and nurse satisfaction, and
      patient safety. Its impact on physicians has not been described. This study was
      undertaken to develop a fuller understanding of the collaboration experience and
      its outcomes. METHODS: Twenty-five medical residents, 32 staff nurses, 5
      physician and 5 nurse faculty wrote narratives about successful collaboration;
      the narratives were then qualitatively analyzed. Narrative analysis was the
      initial qualitative method iteratively employed to identify themes. A
      phenomenological approach was subsequently used to develop a framework for
      collaborative competence. RESULTS: Collaboration triggers, facilitative
      behaviors, outcomes and collaborative competence were the themes identified.
      Affect was identified in the triggers leading to collaboration and in its
      outcomes. Practioners typically entered a care episode feeling worried, uncertain
      or inadequate and finished the interaction feeling satisfied, understood and
      grateful to their colleagues. The frequency of affective experience was not
      altered by gender, profession, or ethnicity. These experiences were particularly
      powerful for novice practioners of both disciplines and appear to have both
      formative and transformative potential. Collaborative competence was
      characterized by a series of graduated skills in clinical and relational domains.
      Many stories took place in the ICU and afterhours settings. CONCLUSIONS: Despite
      the prevailing wisdom that nursing and medicine are qualitatively different, the
      stories from this study illuminate surprising commonalities in the collaboration
      experience, regardless of gender, age, experience, or profession. Collaborative
      competence can be defined and its component skills identified. Contexts of care
      can be identified that offer particularly rich opportunities to foster
      interprofessional collaboration.

PMID- 19089505
TI  - What do patients choose to tell their doctors? Qualitative analysis of potential
      barriers to reattributing medically unexplained symptoms.
AB  - BACKGROUND: Despite both parties often expressing dissatisfaction with
      consultations, patients with medically unexplained symptoms (MUS) prefer to
      consult their general practitioners (GPs) rather than any other health
      professional. Training GPs to explain how symptoms can relate to psychosocial
      problems (reattribution) improves the quality of doctor-patient communication,
      though not necessarily patient health. OBJECTIVE: To examine patient experiences
      of GPs' attempts to reattribute MUS in order to identify potential barriers to
      primary care management of MUS and improvement in outcome. DESIGN: Qualitative
      study. PARTICIPANTS: Patients consulting with MUS whose GPs had been trained in
      reattribution. A secondary sample of patients of control GPs was also interviewed
      to ascertain if barriers identified were specific to reattribution or common to
      consultations about MUS in general. APPROACH: Thematic analysis of in-depth
      interviews. RESULTS: Potential barriers include the complexity of patients'
      problems and patients' judgements about how to manage their presentation of this
      complexity. Many did not trust doctors with discussion of emotional aspects of
      their problems and chose not to present them. The same barriers were seen amongst
      patients whose GPs were not trained, suggesting the barriers are not particular
      to reattribution. CONCLUSIONS: Improving GP explanation of unexplained symptoms
      is insufficient to reduce patients' concerns. GPs need to (1) help patients to
      make sense of the complex nature of their presenting problems, (2) communicate
      that attention to psychosocial factors will not preclude vigilance to physical
      disease and (3) ensure a quality of doctor-patient relationship in which patients
      can perceive psychosocial enquiry as appropriate.

PMID- 19089509
TI  - Age bias and individual variability in stress cardiomyopathy syndromes: mere
      observations or answers?

PMID- 19089508
TI  - Home buprenorphine/naloxone induction in primary care.
AB  - BACKGROUND: Buprenorphine can be used for the treatment of opioid dependence in
      primary care settings. National guidelines recommend directly observed initial
      dosing followed by multiple in-clinic visits during the induction week. We
      offered buprenorphine treatment at a public hospital primary care clinic using a
      home, unobserved induction protocol. METHODS: Participants were opioid-dependent
      adults eligible for office-based buprenorphine treatment. The initial physician
      visit included assessment, education, induction telephone support instructions,
      an illustrated home induction pamphlet, and a 1-week buprenorphine/naloxone
      prescription. Patients initiated dosing off-site at a later time. Follow-up with
      urine toxicology testing occurred at day 7 and thereafter at varying intervals.
      Primary outcomes were treatment status at week 1 and induction-related events:
      severe precipitated withdrawal, other buprenorphine-prompted withdrawal symptoms,
      prolonged unrelieved withdrawal, and serious adverse events (SAEs). RESULTS:
      Patients (N = 103) were predominantly heroin users (68%), but also prescription
      opioid misusers (18%) and methadone maintenance patients (14%). At the end of
      week 1, 73% were retained, 17% provided induction data but did not return to the
      clinic, and 11% were lost to follow-up with no induction data available. No cases
      of severe precipitated withdrawal and no SAEs were observed. Five cases (5%) of
      mild-to-moderate buprenorphine-prompted withdrawal and eight cases of prolonged
      unrelieved withdrawal symptoms (8% overall, 21% of methadone-to-buprenorphine
      inductions) were reported. Buprenorphine-prompted withdrawal and prolonged
      unrelieved withdrawal symptoms were not associated with treatment status at week
      1. CONCLUSIONS: Home buprenorphine induction was feasible and appeared safe.
      Induction complications occurred at expected rates and were not associated with
      short-term treatment drop-out.

PMID- 19089510
TI  - Identifying key components for an effective case report poster: an observational
      study.
AB  - BACKGROUND: Residents demonstrate scholarly activity by presenting posters at
      academic meetings. Although recommendations from national organizations are
      available, evidence identifying which components are most important is not.
      OBJECTIVE: To develop and test an evaluation tool to measure the quality of case
      report posters and identify the specific components most in need of improvement.
      DESIGN: Faculty evaluators reviewed case report posters and provided on-site
      feedback to presenters at poster sessions of four annual academic general
      internal medicine meetings. A newly developed ten-item evaluation form measured
      poster quality for specific components of content, discussion, and format (5
      point Likert scale, 1 = lowest, 5 = highest). MAIN OUTCOME MEASURE(S): Evaluation
      tool performance, including Cronbach alpha and inter-rater reliability, overall
      poster scores, differences across meetings and evaluators and specific components
      of the posters most in need of improvement. RESULTS: Forty-five evaluators from
      20 medical institutions reviewed 347 posters. Cronbach's alpha of the evaluation
      form was 0.84 and inter-rater reliability, Spearman's rho 0.49 (p < 0.001). The
      median score was 4.1 (Q1 -Q3, 3.7-4.6)(Q1 = 25th, Q3 = 75th percentile). The
      national meeting median score was higher than the regional meetings (4.4 vs, 4.0,
      P < 0.001). We found no difference in faculty scores. The following areas were
      identified as most needing improvement: clearly state learning objectives, tie
      conclusions to learning objectives, and use appropriate amount of words.
      CONCLUSIONS: Our evaluation tool provides empirical data to guide trainees as
      they prepare posters for presentation which may improve poster quality and
      enhance their scholarly productivity.

PMID- 19089512
TI  - Hepatocellular carcinoma: resection or transplantation.
AB  - Management of hepatocellular carcinoma in the early cirrhotic remains
      controversial. The exact role of liver transplantation versus resection remains
      to be determined. The following short review attempts to present the evidence for
      the respective roles of liver transplantation versus liver resection in early
      stage HCC.

PMID- 19089511
TI  - Prevalence and trends of receipt of cancer screenings among US women with
      diagnosed diabetes.
AB  - BACKGROUND: Diabetes increases the risk of breast and colorectal cancers and has
      an undetermined relationship to cervical cancer. Improved screenings for these
      cancers are effective in reducing cancer mortality. OBJECTIVES: To examine the
      prevalence of receiving recommended screenings for these cancers and to assess
      the trends in the screening rates over time among US women with diagnosed
      diabetes in comparison with women without diabetes. DESIGN: Cross-sectional.
      PARTICIPANTS: A total of 63,650 to 182,168 adult women participated in the 1996
      2006 (biennially) Behavioral Risk Factor Surveillance System. METHODS: The
      prevalence of receiving cancer screenings was age-standardized to the 2000 US
      population. The adjusted prevalence and adjusted odds ratios (AORs) with 95%
      confidence intervals (CIs) were estimated using logistic regression analyses. The
      linear trends in the screening rates were tested using orthogonal polynomial
      contrasts. RESULTS: In 2006, women with diabetes had a lower adjusted prevalence
      (74% versus 79%, P < 0.05) and the AOR (0.73, 95% CI: 0.66-0.81) for receiving
      cervical cancer screenings, but had a higher adjusted prevalence (63% versus 60%,
      P < 0.05) and the AOR (1.14, 95% CI: 1.04-1.24) for receiving colorectal cancer
      screenings compared to those without. In both women with diabetes and those
      without, the screening rate for colorectal cancer increased linearly during 2002
      2006, whereas the screening rates for breast and cervical cancers changed little
      during 1996-2006. CONCLUSION: Women with diabetes were equally likely to be
      screened for breast cancer, less likely to be screened for cervical cancer, but
      more likely to be screened for colorectal cancer compared to those without.
      Overall, the screening rates in both groups remain below the recommended levels.

PMID- 19089513
TI  - Novel presentation of a familial pancreatic cancer syndrome.
AB  - INTRODUCTION: Earlier detection of pancreatic cancer may help identify patients
      for whom surgical intervention could provide cure or prolong life. In this
      article, we report the occurrence of breast cancer, melanoma, squamous cell
      carcinoma of the alveolar ridge, colon cancer, a desmoid tumor of the abdominal
      wall, and pancreatic adenocarcinoma in a 65-year-old woman. She was identified as
      having the familial atypical multiple mole melanoma-pancreatic cancer syndrome
      (FAMMM-PC) with a germline p16 mutation at amino acid position 15. DISCUSSION:
      Patients with this syndrome traditionally present with multiple nevi and
      melanoma, and a subset also present with other cancers, including pancreatic
      cancer; however, no FAMMM-PC patient has yet been described with this
      constellation of cancers, including squamous cell carcinoma of the alveolar ridge
      and a desmoid tumor. Recognition of the tumors this population of patients is
      susceptible to developing and their genetic associations can help guide the
      surgeon in screening, surveillance, and eventually prevention of many of these
      cancers.

PMID- 19089514
TI  - Validation of an English version of the Padova quality of life instrument to
      assess quality of life following ileal pouch anal anastomosis.
AB  - OBJECTIVE: Ileal pouch anal anastomosis (IPAA) is the procedure of choice for
      most patients requiring surgery for ulcerative colitis and familial adenomatous
      polyposis because of its perceived improvement in health-related quality of life
      (HRQL). The aims of this cross-sectional study were to validate an English
      version of the Padova Inflammatory Bowel Disease Quality of Life questionnaire
      (PIBDQL) in patients undergoing IPAA and to investigate the pre- and
      postoperative predictors of long-term HRQL. MATERIALS AND METHODS: In May 2005,
      the English version of the PIBDQL, Short Inflammatory Bowel Disease
      Questionnaire, and the SF-36 were mailed to 1,379 patients who underwent IPAA at
      the Mount Sinai Hospital between 1982 and 2004. The test-retest reliability,
      internal consistency, construct validity, and discriminative ability of the
      English version of the PIBDQL were assessed. RESULTS: Nine hundred fifty-five
      patients (69%) (475 female, 480 male; mean, age 43 years) returned the
      questionnaires. The mean PIBDQL score was 21.1 (3.4), suggesting good quality of
      life. Test-retest reliability [intraclass correlation coefficient (ICC) = 0.784]
      and internal consistency (Cronbach's alpha = 0.83) were good. Construct validity
      and discriminative ability of the English version of PIBDQL were adequate.
      Multivariate analysis revealed that women (p < 0.01) and Crohn's disease patients
      (p < 0.01) had significantly worse PIBDQL scores. CONCLUSIONS: The English
      version PIBDQL is a reliable and valid disease-specific instrument for assessing
      quality of life in patients with IPAA. In this series, female gender and CD were
      significant predictors of worse HRQL.

PMID- 19089515
TI  - Adenocarcinoma of the appendix is rarely detected by colonoscopy.
AB  - INTRODUCTION: Appendiceal tumors represent a subset of colonic neoplasms that
      frequently defy early diagnosis only to present at advanced stage with peritoneal
      metastasis. Data on early detection by colonoscopy is limited to case reports or
      series. The aim of this study is to determine the diagnostic yield of colonoscopy
      in detecting appendiceal lesions in patients with appendiceal adenocarcinoma and
      pseudomyxoma peritonei. METHODS: We reviewed clinicopathologic data on 121
      consecutive patients with histologically confirmed appendiceal adenocarcinoma
      with pseudomyxoma peritonei presenting to our institution for intraperitoneal
      hyperthermic chemotherapy (IPHC) and cytoreductive surgery between February, 1993
      and August, 2007, focusing on the colonoscopy findings. RESULTS: Preoperative
      colonoscopic data were available on 64 patients (average age = 51; 52 for IPHC
      patients). Abnormal findings included seven patients with appendiceal lesions
      (11%), 12 patients with cecal abnormalities (19%), and 28 patients with polyps
      (44%). Twenty-three patients (36%) had a normal colonoscopy. Malignancy was
      documented in two of the 64 (3.1%) patients on preoperative colonoscopy biopsies.
      CONCLUSIONS: Appendiceal abnormalities are infrequently seen on colonoscopy and
      rarely yield a diagnostic biopsy in patients with appendiceal carcinoma. We found
      that nearly 42% of patients with carcinoma of the appendix have synchronous
      colonic polyps, a much higher prevalence than would be expected, supporting a
      role for a perioperative colonoscopy.

PMID- 19089516
TI  - Increased fat content and body shape have little effect on the accuracy of lymph
      node retrieval and blood loss in laparoscopic distal gastrectomy for gastric
      cancer.
AB  - BACKGROUND: Fat volume and large abdominal shape are known to disrupt the
      procedures of lymph node retrieval used in gastric cancer surgery. The present
      study examined the effect of increasing fat content on surgical outcomes,
      including estimated blood loss and the number of lymph nodes retrieved during
      gastrectomy. METHODS: Of 154 patients, 50 underwent the conventional open
      procedure (OPEN) and 104 underwent laparoscopy-assisted distal gastrectomy
      (LADG). The BMI-related factors of total fat, subcutaneous fat, and visceral fat
      area, as well as the peritoneum-celiac axis distance were calculated by computed
      tomography. Regression analysis was used to determine the effects of BMI-related
      factors that obstruct the surgical procedures on the specific outcomes of
      estimated blood loss and the number of lymph nodes retrieved. RESULTS: In the
      OPEN, but not in the LADG, increases in all BMI-related factors were related to
      increases in estimated blood loss. The increases in BMI, subcutaneous fat, and
      the peritoneum-celiac axis distances were related to decreased numbers of
      retrieved lymph nodes only in the OPEN. Only the factor of visceral fat at the
      celiac level was modestly associated with a decreased number of dissected lymph
      node in both groups. CONCLUSIONS: The present study demonstrated that increased
      fat content and large body shape have little effect on the number of lymph nodes
      retrieved and blood loss in LADG. However, for patients undergoing conventional
      open distal gastrectomy, increased fat content and large body shape do impact on
      the amount of blood lost and the number of lymph nodes retrieved.

PMID- 19089517
TI  - Determining pattern of recurrence following pancreaticoduodenectomy and adjuvant
      5-flurouracil-based chemoradiation therapy: effect of number of metastatic lymph
      nodes and lymph node ratio.
AB  - BACKGROUND: There are limited data on patterns of recurrence and factors
      associated with local recurrence following pancreaticoduodenectomy for pancreatic
      adenocarcinoma and adjuvant 5-flurouracil-based chemoradiation therapy. METHODS
      AND MATERIALS: Between 1995 and 2005, 905 patients underwent
      pancreaticoduodenectomy for pancreatic adenocarcinoma; 154 patients had complete
      pattern of recurrence data available. RESULTS: At median follow-up of 20.2
      months, 103 (66.9%) patients recurred with median time to recurrence of 16.2
      months. Most patients recurred with distant disease only (68.9%), while 21.4%
      patients recurred with local disease only; ten (9.7%) patients recurred with
      local and distant disease. Several factors were associated with local recurrence:
      poor tumor differentiation (hazards ration [HR] 2.39) and presence of metastatic
      lymph nodes (HR 1.89, both p < 0.05). Among N1 patients, poor tumor
      differentiation (HR 3.92), >5 metastatic LN (HR 3.75), and lymph node ratio (LNR)
      >0.4 (HR 2.96) had the highest risk of local recurrence (all p < 0.05).
      Increasing LNR was associated with an incremental increased risk of local
      recurrence (LNR <0.2, 21.3% versus LNR >or=0.2 to 0.4, 25.2% versus LNR >0.4,
      40.4%; p < 0.05). CONCLUSIONS: Although most patients who receive standard 5
      flurouracil-based chemoradiation therapy will ultimately succumb to distant
      disease, about 30% recur locally. Poor tumor differentiation, a high number of
      metastatic LN (>5), and LNR >0.4 are associated with the highest risk of local
      failure. In these patients, radiation dose escalation and/or a combination of
      radiation with novel chemotherapeutic agents may be necessary to improve
      outcomes.

PMID- 19089518
TI  - Succinylcholine: a useful drug in bariatric surgery.

PMID- 19089519
TI  - Gastric emptying is not affected by sleeve gastrectomy--scintigraphic evaluation
      of gastric emptying after sleeve gastrectomy without removal of the gastric
      antrum.
AB  - BACKGROUND: The aim of this study is to clarify whether laparoscopic sleeve
      gastrectomy (LSG) to treat morbid obesity causes changes in gastric emptying.
      METHODS: Gastric emptying scintigraphy was performed before and 3 months after
      LSG, in 21 consecutive morbidly obese patients. After an overnight fast, subjects
      consumed a standard semi-solid meal, to which 0.5 mCi Tc99-labeled sulfur colloid
      had been added. The meal was consumed within 10 min. Scintigraphic imaging was
      performed with a gamma camera immediately after the completion of the meal as
      well as after 30, 60, 120, 180, and 240 min. Quantitative and qualitative
      analysis was performed by drawing a region of interest (ROI) enclosing the
      stomach on the anterior and the posterior images. Time 0 was considered the time
      of meal completion (all the ingested activity) and was defined as 100% retention.
      The same ROI was used on all consecutive images of the same projection for the
      same patient. The geometric mean of the anterior and the posterior counts for
      each time point is calculated and corrected for Tc(99m) decay. Gastric emptying
      curves were constructed. T 1/2 is the time interval between completion of the
      meal and the point at which half of the meal (by radioactivity counts) has left
      the stomach. Retention is expressed as the percent remaining in the stomach at
      each time point (half, 1, 2, 3, 4 h). RESULTS: The mean T 1/2 raw data was
      62.39+/-19.83 and 56.79+/-18.72 min (p=0.36, t=-0.92, NS) before and 3 months
      after LSG, respectively. The T 1/2 linear was 103.64+/-9.82 and 106.92+/-14.55,
      (p=0.43, t=-0.43, NS), and the linear fit slope 0.48+/-0.04 and 0.47+/-0.05
      (p=0.48, t=0.7, NS). CONCLUSIONS: LSG with antrum preservation as performed in
      this series has no effect on gastric emptying.

PMID- 19089520
TI  - A rare complication after laparoscopic gastric banding: connecting-tube
      penetration into the hilus of the kidney.
AB  - Laparoscopic adjustable gastric banding is a common operation for morbid obesity.
      Late complications mainly originate from either the injection port (dislocation,
      infection, leakage) or the gastric band (pouch dilatation, slippage, leakage,
      gastric erosion). Complications from the tube, connecting the port with the band,
      are rarely described. We report the penetration of a loose connecting tube into
      the kidney 8 months after removal of an infected injection port.

PMID- 19089521
TI  - The classic: Treatment of malum coxae senilis, old slipped upper femoral
      epiphysis, intrapelvic protrusion of the acetabulum, and coxa plana by means of
      acetabuloplasty. 1936.

PMID- 19089522
TI  - Correcting residual deformity following clubfoot releases.
AB  - There are many possible pitfalls of clubfoot releases and it is important to
      recognize the problems and provide proper timely treatment. Late residual
      deformity following clubfoot releases include: dynamic or stiff supination and
      forefoot adduction deformities, intoeing gait, overcorrection, rotatory dorsal
      subluxation of the navicular, vascular insult to the talus with collapse, and
      dorsal bunion. We reviewed 134 clubfeet in 95 children who had primary clubfoot
      releases between 1988 and 1991. In general, the patients who underwent surgery
      before 6 months of age had poorer results compared with older children. Twenty
      one feet (15.7%) underwent additional procedures. The most common additional
      procedure was split anterior tibial tendon transfer. Not all patients with
      residual deformities underwent additional procedures. In treating recurrent and
      residual deformity following a clubfoot surgery, it is most important to keep
      function in mind. From this series of patients treated with comprehensive
      clubfoot release, we have identified the most common residual deformities
      encountered after the initial release and effective surgical treatment when
      necessary. LEVEL OF EVIDENCE: Level IV, therapeutic study. See the Guidelines for
      Authors for a complete description of levels of evidence.

PMID- 19089523
TI  - Bone scintigraphy in femoroacetabular impingement: a preliminary report.
AB  - Femoroacetabular impingement (FAI) has recently been recognized as a cause of hip
      pain, labral tears, and cartilage damage in young adults. We determined the
      sensitivity and specificity of bone scans in diagnosing FAI and describe its
      findings on nuclear imaging. We prospectively followed 25 patients with hip pain
      (four bilateral) of greater than 6 months' duration and a positive impingement
      sign (IS). All patients had plain radiographs and a three-phase bone scan
      followed by single-photon emission computed topographic (SPECT) images of both
      hips. We presumed patients had FAI if they had all three of the following
      findings: hip pain, positive IS, and diagnostic radiographs. Forty-six of the 50
      hips had bony abnormalities on radiographs and 26 hips were diagnosed with FAI
      according to our criteria. Twenty-two of these 26 hips showed an increased uptake
      on SPECT representing true-positives. There were four false-positives, nine false
      negatives, and 15 true-negatives. Sensitivity of bone SPECT was 84.7%,
      specificity 62.5%, positive predictive value 71%, and negative predictive value
      78.9%. Focal uptake was localized to the superolateral acetabular rim and/or
      anterolateral femoral head-neck junction consistent with the reported intra
      articular cartilage hip damage seen in FAI.

PMID- 19089524
TI  - Femoroacetabular impingement treatment using arthroscopy and anterior approach.
AB  - Femoroacetabular impingement (FAI) has been identified as a common cause of hip
      pain in young adults. However, treatment is not well standardized. We
      retrospectively reviewed 97 patients (100 hips) who underwent osteochondroplasty
      of the femoral head-neck for FAI using a mini-open anterior Hueter approach with
      arthroscopic assistance. The mean age of the patients was 33.4 years. The labrum
      was refixed in 40 hips, partially excised in 39 cases, completely excised in 14
      cases, and left intact in seven. Six patients were lost to followup, leaving 91
      (94 hips) with a minimum followup of 28.6 months (mean, 58.3 months; range, 28.6
      104.4 months). We assessed patients clinically using the nonarthritic hip score
      (NAHS). One patient had a femoral neck fracture 3 weeks postoperatively. At the
      last followup, the mean NAHS score increased by 29.1 points (54.8 +/- 12
      preoperatively to 83.9 +/- 16 points at last followup). Eleven hips developed
      osteoarthritis and subsequently had total hip arthroplasty. The best results were
      obtained in patients younger than 40 years old with a 0 Tonnis grade. Refixation
      of the labrum did not correlate with a higher NAHS score (87 +/- 11 with
      refixation versus 82 +/- 19 points without) at the last followup. The technique
      for FAI treatment allowed direct visualization of the anterior femoral head-neck
      junction while avoiding surgical dislocation, had a low complication rate, and
      improved functional scores.

PMID- 19089525
TI  - Spinocerebellar ataxia type 23: a genetic update.
AB  - The spinocerebellar ataxia type 23 locus was identified in 2004 based on linkage
      analysis in a large, two-generation Dutch family. The age of onset ranged 43-56
      years and the phenotype was characterized by a slowly progressive, isolated
      ataxia. Neuropathological examination revealed neuronal loss in the Purkinje cell
      layer, dentate nuclei, and inferior olives. Ubiquitin-positive intranuclear
      inclusions were found in nigral neurons, but were considered to be Marinesco
      bodies. The disease locus on chromosome 20p13-12.3 was found to span a region of
      approximately 6 Mb of genomic DNA, containing 97 known or predicted genes. To
      date, no other families have been described that also map to this SCA locus.
      Direct sequencing of the coding regions of 21 prioritized candidate genes did not
      reveal any disease-causing mutation. Apparently, the SCA23 gene is a disease gene
      with a different function than the genes that have been associated with other
      known SCA types. Work to elucidate the chromosomal organization of the SCA23
      locus will eventually discover the responsible disease gene.

PMID- 19089526
TI  - The use of sterilised polyester mosquito net mesh for inguinal hernia repair in
      Ghana.
AB  - BACKGROUND: The use of alloplastic mesh is now commonplace in hernia repair.
      However, in developing countries, cheaper alternatives to commercial mesh are
      required due to the high associated cost. Whilst nylon mosquito net mesh has been
      trialled previously, this study aimed to assess the use of polyester mosquito net
      mesh in tension-free inguinal hernia repair in Ghana. METHODS: All patients
      undergoing inguinal hernia repair during the 5-day 'Operation Hernia' mission in
      2007 were eligible for the study. A piece of sterilised 10 x 15-cm 100% polyester
      mosquito net mesh, manufactured and donated by Scotmas Limited, was implanted for
      all tension-free hernia repairs. The surgeons' ease of handling and incidence of
      complications at 6 weeks and 6 months were assessed. RESULTS: Ninety-five
      patients underwent inguinal hernia repair using a total of 106 polyester mosquito
      net meshes. The mean (range) age of patients was 44.3 (15-78) years. Seventy-two
      (76%) were repaired using local anaesthesia. At 6 weeks and 6 months, a total of
      seven (7%) patients suffered wound complications (five haematomas, two wound
      infections). Ease of practical handling improved after the first 2-5 cases. The
      cost of an individual 10 x 15-cm mesh was estimated at US$0.0072-0.014, and the
      cost of sterilisation and packaging was US$1.46 per mesh. CONCLUSIONS: Polyester
      mosquito net mesh represents a cost-effective alternative to commercial meshes in
      developing countries, with a relatively low rate of early complications and
      similar short-term recurrence rates. The use of local anaesthesia may enhance
      this further.

PMID- 19089527
TI  - Post hemipelvectomy incisional hernia.
AB  - Incisional hernia is a very rare complication after hemipelvectomy. Very few
      references are reported in the literature. A rare case of post hemipelvectomy
      incisional hernia is presented with a unique method of reconstruction using a
      combination of monofilament polypropylene mesh and a de-epithelialized skin flap
      in such a way that it provided double breasting of dermal flaps.

PMID- 19089528
TI  - TrgI, toluene repressed gene I, a novel gene involved in toluene-tolerance in
      Pseudomonas putida S12.
AB  - Pseudomonas putida S12 is well known for its remarkable solvent tolerance.
      Transcriptomics analysis of this bacterium grown in toluene-containing chemostats
      revealed the differential expression of 253 genes. As expected, the genes
      encoding one of the major solvent tolerance mechanisms, the solvent efflux pump
      SrpABC and its regulatory genes srpRS were heavily up-regulated. The increased
      energy demand brought about by toluene stress was also reflected in
      transcriptional changes: genes involved in sugar storage were down-regulated
      whereas genes involved in energy generation such as isocitrate dehydrogenase and
      NADH dehydrogenases, were up-regulated in the presence of toluene. Several
      flagella-related genes were up-regulated and a large group of transport genes
      were down-regulated. In addition, a novel Pseudomonas-specific gene was
      identified to be involved in toluene tolerance of P. putida S12. This toluene
      repressed gene, trgI, was heavily down-regulated immediately upon toluene
      exposure in batch cultures. The relationship of trgI with solvent tolerance was
      confirmed by the increased resistance to toluene shock and toluene induced lysis
      of trgI knock-out mutants. We propose that down-regulation of trgI plays a role
      in the first line of defence against solvents.

PMID- 19089529
TI  - Temperature downshift induces antioxidant response in fungi isolated from
      Antarctica.
AB  - Although investigators have been studying the cold-shock response in a variety of
      organisms for the last two decades or more, comparatively little is known about
      the difference between antioxidant cell response to cold stress in Antarctic and
      temperate microorganisms. The change of environmental temperature, which is one
      of the most common stresses, could be crucial for their use in the
      biotechnological industry and in ecological research. We compared the effect of
      short-term temperature downshift on antioxidant cell response in Antarctic and
      temperate fungi belonging to the genus Penicillium. Our study showed that
      downshift from an optimal temperature to 15 degrees or 6 degrees C led to a cell
      response typical of oxidative stress: significant reduction of biomass
      production; increase in the levels of oxidative damaged proteins and accumulation
      of storage carbohydrates (glycogen and trehalose) in comparison to growth at
      optimal temperature. Cell response against cold stress includes also increase in
      the activities of SOD and CAT, which are key enzymes for directly scavenging
      reactive oxygen species. This response is more species-dependent than dependent
      on the degree of cold-shock. Antarctic psychrotolerant strain Penicillium olsonii
      p14 that is adapted to life in extremely cold conditions demonstrated enhanced
      tolerance to temperature downshift in comparison with both mesophilic strains
      (Antarctic Penicillium waksmanii m12 and temperate Penicillium sp. t35).

PMID- 19089530
TI  - Archaeal and bacterial communities of heavy metal contaminated acidic waters from
      zinc mine residues in Sepetiba Bay.
AB  - Mining of metallic sulfide ore produces acidic water with high metal
      concentrations that have harmful consequences for aquatic life. To understand the
      composition and structure of microbial communities in acid mine drainage (AMD)
      waters associated with Zn mine tailings, molecular diversity of 16S genes was
      examined using a PCR, cloning, and sequencing approach. A total of 78 operational
      taxonomic units (OTUs) were obtained from samples collected at five different
      sites in and around mining residues in Sepetiba Bay, Brazil. We analyzed metal
      concentration, physical, chemical, and microbiological parameters related to
      prokaryotic diversity in low metal impacted compared to highly polluted
      environments with Zn at level of gram per liter and Cd-Pb at level of microgram
      per liter. Application of molecular methods for community structure analyses
      showed that Archaea and Bacteria groups present a phylogenetic relationship with
      uncultured environmental organisms. Phylogenetic analysis revealed that bacteria
      present at the five sites fell into seven known divisions, alpha-Proteobacteria
      (13.4%), beta-Proteobacteria (16.3%), gamma-Proteobacteria (4.3%),
      Sphingobacteriales (4.3%), Actinobacteria (3.2%) Acidobacteria (2.1%),
      Cyanobacteria (11.9%), and unclassified bacteria (44.5%). Almost all archaeal
      clones were related to uncultivated Crenarchaeota species, which were shared
      between high impacted and low impacted waters. Rarefaction curves showed that
      bacterial groups are more diverse than archaeal groups while the overall
      prokaryotic biodiversity is lower in high metal impacted environments than in
      less polluted habitats. Knowledge of this microbial community structure will help
      in understanding prokaryotic diversity, biogeography, and the role of
      microorganisms in zinc smelting AMD generation and perhaps it may be exploited
      for environmental remediation procedures in this area.

PMID- 19089531
TI  - Non-convulsive status epilepticus following antibiotic therapy as a cause of
      unexplained loss of consciousness in patients with renal failure.
AB  - BACKGROUND: Non-convulsive status epilepticus (NCSE): a condition that may be
      associated with different levels of altered consciousness without any apparent
      motor signs. There are published reports that it may be associated with
      antibiotic use patients with renal failure. METHOD: This is a retrospective
      analysis of our 12 NCSE (2 men, 10 women, a mean age: 58.4 +/- 17.5 range of 29
      85 years) patients with renal failure who have used antibiotics. RESULTS: Twelve
      patients were receiving a total of 19 antibiotics including mainly beta-lactams.
      The mean duration of time between start of antibiotic treatment and NCSE was 8.0
      (3-21) days. In all of the patients, neurological symptoms were slowly
      progressive and consisted of depression of consciousness and/or disorientation.
      Diazepam administration resulted in marked reduction or completely disappears of
      epileptic activity. Four of 12 patients (33%) died, but none of were associated
      with NCSE but primarily associated with infection developed secondary to the
      preexisting disease and with congestive heart failure which patients already had.
      CONCLUSION: Antibiotics, especially beta-lactams could be neurotoxic and may
      cause of NCSE. NCSE should be considered in patients with unexplained loss of
      consciousness; EEG must be a part of investigations in patients with uraemia
      receiving antibiotics.

PMID- 19089532
TI  - Efficacy and safety of rebamipide for the treatment of dry mouth symptoms in
      patients with Sjogren's syndrome: a double-blind placebo-controlled multicenter
      trial.
AB  - The effects of rebamipide on dry mouth and salivary secretion in Sjogren's
      syndrome patients were investigated in a double-blind placebo-controlled study.
      Rebamipide (100 mg TID) or placebo was administered for eight weeks and patient
      assessed improvement of dry mouth and increase in salivary secretion measured by
      the Saxon test were evaluated. At two, four, and eight weeks, dry mouth
      improvement rates were, respectively, 26.0, 44.0, and 46.9% for rebamipide and
      20.0, 27.1, and 39.1% for placebo, and mean increases in salivary secretion were,
      respectively, 0.14, 0.24, and 0.35 g for rebamipide and 0.03, 0.09, and 0.17 g
      for placebo, indicating higher values in the rebamipide group for both parameters
      at all timepoints but no significant differences between the two groups. Analysis
      by baseline characteristics suggested a statistically significant salivary
      secretion increasing effect of rebamipide in cases of primary Sjogren's syndrome.
      No difference in the incidence of adverse events was seen between the two groups,
      confirming the safety of rebamipide. As a salivary secretion increasing effect
      was strongly suggested in cases of primary Sjogren's syndrome, further study on
      the administration of rebamipide for the treatment of dry mouth in patients with
      Sjogren's syndrome is required.

PMID- 19089533
TI  - Clinical and histopathological features of myopathies in Japanese patients with
      anti-SRP autoantibodies.
AB  - To elucidate the clinical and histopathological features associated with
      autoantibodies to the signal recognition particle (SRP), we have studied 23
      Japanese patients with this specificity among 3,500 patients with
      polymyositis/dermatomyositis and other connective tissue diseases. Anti-SRP
      antibodies were determined based on analysis of RNA and protein components by
      immunoprecipitation assays. The pathological analysis was performed by using
      special stainings including alkaline phosphatase, myosin ATPase, and modified
      Gomori trichrome stainings. Twenty-one (92%) of these 23 patients had myositis, 8
      of whom (38%) required cytotoxic agents or intravenous immunoglobulin therapy in
      addition to corticosteroid therapy. Four patients (16%) had rheumatoid arthritis,
      two of whom had no features of myositis. Muscle biopsy specimens of 11 patients
      were examined histologically in detail. All 11 had muscle fiber necrosis and/or
      regeneration, but only one had infiltration of inflammatory cells. Six of the 11
      (55%) patients showed type I fiber predominance by ATPase staining, while eight
      control myositis patients without anti-SRP antibodies did not. There was no
      correlation of other neurogenic features in histology with the presence of anti
      SRP antibodies. These studies suggest that anti-SRP autoantibodies are most
      likely to be related to myopathies that are resistant to corticosteroid therapy
      and without inflammation histopathologically.

PMID- 19089534
TI  - Two subtypes of radiographic osteoarthritis in the distal interphalangeal joint
      of the hand.
AB  - BACKGROUND: The etiology and pathogenesis of hand osteoarthritis (OA) are not
      completely clarified, and several factors may cooperate in a multifactorial
      fashion in its development. The purpose of this study was to clarify the effects
      of the dominant hand that contribute to the development of distal interphalangeal
      (DIP) joint OA using epidemiological analyses. METHODS: A total of 518 subjects
      (156 men, 362 women) in a rural community were analyzed. Their mean age was 63.8
      years for men and 60.7 years for women. Anteroposterior (AP) standing radiographs
      of bilateral knees, lateral views of the lumbar spine, and AP views of bilateral
      hands were obtained. Furthermore, a survey of their life patterns was conducted
      using self-administered questionnaires. Radiographic osteoarthritis was defined
      as Kellgren and Lawrence grade 2 or higher. Hand OA was limited to Heberden's
      nodes. Generalized OA (GOA) was defined as bilateral knee OA plus lumbar spine
      OA. RESULTS: GOA was observed in 13.0% of the subjects. The incidence of DIP
      joint OA was significantly higher in the GOA group than that in the non-GOA
      group. In the GOA group, the incidence of right-hand DIP joint OA in right-handed
      and left-handed subjects was 37.5% and 40.0%, respectively, without a significant
      difference. In the non-GOA group, however, the incidence of right-hand DIP joint
      OA in right-handed and left-handed subjects was 16.4% and 3.2%, respectively,
      with a significant difference. With a multiple logistic regression model, the P
      value of the handedness was marginal (0.060), but a clear tendency of increase in
      the odds ratio (7.129) was observed in the dominant hand for the non- GOA group.
      In contrast, there was no effect of the handedness on right-hand DIP joint OA in
      the GOA group. CONCLUSIONS: There are two subtypes of hand DIP joint OA in terms
      of the etiology. One is environmental, and the other is genetic.

PMID- 19089535
TI  - Diagram specific to sacroiliac joint pain site indicated by one-finger test.
AB  - BACKGROUND: The sacroiliac joint (SIJ) can be a source of low back and lower limb
      pain. The SIJ pain can originate not only from the joint space but also from the
      ligaments supporting the joint. Its diagnosis has been difficult because the
      physical and radiological examinations have proved less than satisfactory. Thus,
      to know the specific sites of SIJ pain, if these exist, could be very useful for
      making the diagnosis. The purpose of the present study was to identify the main
      site of SIJ pain according to the patient's pointing with one finger and to
      confirm the site by a pain-provocation test and periarticular lidocaine
      injection. METHODS: Forty-six of 247 consecutive patients with low back pain at
      our outpatient clinic, who could indicate with one finger the main site of the
      pain, which presented at only one site and was reproducible, were the subjects of
      this study. The main site of pain was anatomically confirmed by fluoroscopy.
      Then, a periarticular SIJ injection was performed. The patients were blindly
      assessed and a diagram of the main site of the SIJ pain was made. RESULTS: There
      were 19 males and 27 females and the age averaged 50 years. Eight patients showed
      a positive placebo response and were excluded from this study. Twenty-five of the
      remaining 38 patients indicated the main site of pain at the posterior-superior
      iliac spine (PSIS) or within 2 cm of the PSIS, and 18 of these patients showed a
      positive effect with periarticular SIJ block. The other 13 patients, including 2
      patients with a positive response to the periarticular block, did not show the
      PSIS as the main site of pain. CONCLUSIONS: Our study clearly indicated that when
      patients point to the PSIS or within 2 cm of it as the main site of low back
      pain, using one finger, the SIJ should be considered as the origin of their low
      back pain.

PMID- 19089536
TI  - Midterm results of the Synergy cementless tapered stem: stress shielding and bone
      quality.
AB  - BACKGROUND: Tapered femoral stems have been shown to produce less thigh pain and
      stress shielding than other cement-less stem designs. The purpose of this study
      was to examine the performance of this type of femoral stem in Japanese patients.
      METHODS: A series of 40 total hip arthroplasties with a Synergy tapered femoral
      component were performed in 33 patients between March 1999 and February 2001 at
      our institution. Three hips (in three patients) were lost to follow-up, so 37
      hips in 30 patients were followed for an average of 70 months. The patients'
      average age at the time of surgery was 59 years (range 43-80 years). Clinical
      evaluation included the Japanese Orthopaedic Association (JOA) Hip Score and the
      incidence of thigh pain. Preoperative radiographic examination included the
      cortical index and Dorr's bone type. Postoperative radiographic examination
      included evaluation of biological fixation, spot welds, cortical hypertrophy, and
      stress shielding. RESULTS: The average JOA Hip Score improved significantly from
      35 preoperatively to 91 postoperatively. No patient suffered thigh pain. All
      femoral components were classified as bony stable. Spot welds and cortical
      hypertrophy were commonly found in the middle to the distal portion of the
      component. Severe (third and fourth degree) stress shielding was observed in
      24.3% of the cases. A low cortical index, a Dorr type C femur, and a large stem
      size were associated with severe stress shielding. CONCLUSIONS: The midterm
      clinical results with the Synergy femoral component were satisfactory for
      Japanese patients. Although severe stress shielding was frequently observed in
      patients with poor bone quality, stem stability was not affected. Extent of grit
      blasting and stem length may be factors causing severe stress shielding in
      Japanese patients with poor bone quality. In conclusion, poor bone quality is a
      less favorable indication for the cementless tapered stem.

PMID- 19089537
TI  - Evaluation of joint laxity against distal traction force upon flexion in cruciate
      retaining and posterior-stabilized total knee arthroplasty.
AB  - BACKGROUND: Several studies have reported varus-valgus stability in the extension
      position after total knee arthroplasty (TKA). However, few studies have evaluated
      joint laxity in the flexion position postoperatively. The purpose of the study
      was to evaluate joint laxity against distal traction force on flexion after
      cruciate-retaining and posterior-stabilized total knee arthroplasties. METHODS: A
      total of 44 knees (22 knees cruciate-retaining, 22 knees posterior-stabilized) in
      40 patients with osteoarthritis were tested in this study. The subjects were
      seated at a table and their knee joints were fixed at 80 degrees of flexion to
      avoid overlapping images of condyles and the femoral shaft. Tibial shafts were
      adjusted to be parallel to the radiographic films, and posteroanterior
      radiographs were obtained. Flexion stress tests were performed with a distal
      traction of 100 N at a neutral foot position. Radiographs were obtained at
      neutral and traction positions. The distance from the perpendicular line of the
      top of the polyethylene insert to the midpoint on the tangential line of the
      femoral condyle was measured (joint space distance) at each side. RESULTS: In the
      flexion-neutral position, average joint space distances were 0.1 +/- 0.2 mm in
      cruciate-retaining (CR) TKA knees and 0.2 +/- 0.3 mm in posterior-stabilized (PS)
      TKA knees. With flexion-traction stress tests, the average joint space distances
      were 0.5 +/- 0. 5 mm in CR TKA knees 2.4 +/- 1.2 mm in PS TKA knees. Average
      changes of joint space distances between the two positions were 0.3 +/- 0.4 mm
      (CR TKA) and 2.2 +/- 1.5 mm (PS TKA). The changes in joint space distances
      between neutral and traction positions of PS TKA knees were significantly larger
      than those of CR TKA knees in flexion stress tests (P < 0.01). CONCLUSION: The
      posterior cruciate ligament acted as a stabilizer against distal traction force
      in the CR-TKA knees. However, the laxity of PS-TKA knees against distal force
      differed among individual cases.

PMID- 19089538
TI  - Three-dimensional ultrasonography of shoulders with rotator cuff tears.
AB  - BACKGROUND: It is possible to evaluate the size of rotator cuff tears by
      ultrasonography (US) or magnetic resonance imaging. However, there are only a few
      reports on the imaging assessment of the configuration of cuff tears, which could
      provide important preoperative information that assists performing an optimal
      anatomical repair. The purpose of this study was to determine quantitatively the
      reproducibility of three-dimensional US in the assessment of rotator cuff tear
      configuration. METHODS: Ten embalmed cadaveric shoulders with rotator cuff tears
      were examined. After resecting the proximal humerus with the rotator cuff, we put
      it in water and scanned it using high-resolution US with a three-dimensional
      linear probe. Actual tear lengths and widths were compared with sonographic
      measurements (Pearson correlation coefficient). By superimposing the real
      photographic image on the reconstructed three-dimensional image, we calculated
      the concordance rate (ratio of the concordance area to the tear area). RESULTS:
      The actual tear length (16.6 +/- 7.1 mm; mean +/- SD) and width (8.4 +/- 4.4 mm)
      were correlated with the tear length (16.4 +/- 7.5 mm) and width (8.2 +/- 4.4 mm)
      measured from reconstructed three-dimensional ultrasonograms (r = 0.998 and
      0.994, respectively). The mean concordance rate was 91.4%, indicating that almost
      exactly the same configuration was reconstructed by US. CONCLUSIONS: Three
      dimensional US is useful for evaluating the configuration of rotator cuff tears.
      This is the first report to quantify the similarity between the configuration
      evaluated by US and the actual configuration. Using this method, we can visualize
      the configuration of rotator cuff tears preoperatively, facilitating optimal
      repair design.

PMID- 19089539
TI  - Changes in gait after bilateral meniscectomy in sheep: effect of two hyaluronan
      preparations.
AB  - BACKGROUND: This study examined the effect of bilateral meniscectomy on ground
      reaction forces (GRFs) in sheep, and the therapeutic effect of two hyaluronan
      (HA) preparations. METHODS: Eighteen sheep were subjected to bilateral lateral
      meniscectomy and were treated from 16 to 20 weeks postoperatively with
      intraarticular Hyalgan (Fidia Farmaceutici), HYADD4-G (a novel amide derivative;
      Fidia Farmaceutici), or saline placebo (n = 6 per group). GRFs were assessed at
      baseline and 6, 12, 16, 22, and 26 weeks postoperatively. Rheological parameters
      and HA content of synovial fluid samples were assessed using micro-Fourier
      rheometry. RESULTS: Meniscectomy significantly reduced GRF and abolished the
      normal two-peak vector. GRF deficits were partially ameliorated by both HA
      preparations: Hyalgan increased peak vertical forces at 6 weeks post-treatment
      (week 22), while HYADD4-G increased vertical impulse post-treatment. Both HA
      treatments, but not saline placebo, restored a twopeak composite force vector at
      6 weeks post-treatment. Neither HA preparation significantly modulated
      osteoarthritis (OA) severity, or synovial fluid parameters. CONCLUSIONS: This
      study showed that GRF responses to bilateral meniscectomy in sheep mimic
      available data for human meniscectomy and OA patients. However, this time course
      suggests that gait deficits are temporally unrelated to observed cartilage or
      synovial fluid changes. The bilateral ovine meniscectomy model demonstrates
      modest but quantifiable changes in GRF that mimic human OA and are amenable to
      modification by known OA therapies such as HA.

PMID- 19089540
TI  - RGD peptide-induced cell death of chondrocytes and synovial cells.
AB  - BACKGROUND: Small peptides including the Arg-Gly-Asp (RGD) motif have been used
      in studies on cell-extracellular matrix (ECM) attachment due to their ability to
      disturb integrin-mediated attachment on the cell surface. As another biological
      action of RGD peptides, several reports have shown that RGD peptides are
      incorporated into cytoplasm and induce apoptosis by direct activation of caspase
      3. This study evaluated the effect of RGD peptides on chondrocytes and synovial
      cells and studied the involvement of caspases. METHODS: Chondrocytes and synovial
      cells were isolated and cultured from the knee joints of New Zealand White
      rabbits. Cells were incubated in serum-free medium with peptides (RGD, RGDS,
      GRGDSP, GRGDNP, RGES), and the survival rates were evaluated. The rate of
      apoptotic cells was measured by flow cytometry in cells treated with RGDS,
      GRGDSP, and RGES. Caspase-3, -8 and -9 activity was measured in cells treated
      with RGDS and GRGDSP. Osteochondral explants harvested from rabbits were also
      incubated with RGD peptides (RGDS, GRGDSP, and GRGDNP), and the survival rate of
      chondrocytes was evaluated. RESULTS: The survival rate of cultured chondrocytes
      was significantly decreased in the GRGDSP- and GRGDNP-treated groups. The
      survival rate of synovial cells was significantly decreased with four of the RGD
      peptides (RGD, RGDS, GRGDSP, and GRGDNP) at 5 mM, and in the RGDS- and GRGDSP
      treated groups at 1 mM. Flow cytometric assay revealed increases of apoptotic
      chondrocytes with GRGDSP and increases of apoptotic synovial cells with RGDS and
      GRGDSP. Caspase-3 was activated in chondrocytes treated with GRGDSP and it was
      also activated in synovial cells treated with RGDS and GRGDSP. Caspases-8 and -9
      were not activated in chondrocytes or in synovial cells. The survival rate of
      chondrocytes in explants decreased in the superficial layer with all three RGD
      peptides (RGDS, GRGDSP, and GRGDNP) and in the middle layer with GRGDSP.
      CONCLUSIONS: RGD peptides induced apoptosis in cultured chondrocytes as well as
      in cells in cartilage explants and synovial cells, presumably through direct
      activation of caspase-3.

PMID- 19089541
TI  - Intermittent administration of human parathyroid hormone (1-34) increases new
      bone formation on the interface of hydroxyapatitecoated titanium rods implanted
      into ovariectomized rat femora.
AB  - BACKGROUND: As hydroxyapatite (HA) has good osteoconductive properties, HA is
      used as coating material for the implants in cementless arthroplasty. However,
      its effect is not sufficient for osteoporotic bone. Parathyroid hormone (PTH) is
      known to have anabolic effects on bone formation. Intermittent administration of
      PTH increases both cancellous and cortical bone mass. The aim of this study was
      to confirm the effect of the fixation strength of HA-coated implants in the
      osteoporotic condition with a mechanical test and a bone histomorphometric
      method. METHODS: Female Sprague-Dawley rats were used for this study. Four weeks
      after ovariectomy (OVX) or sham surgery, HA-coated titanium rods were inserted
      into the distal femoral canal (Sham+HA group and OVX+HA group). PTH was
      administered immediately after the implantation of the HAcoated rods (OVX+HA+P
      group). We measured the shear strength at the bone-implant interface by a push
      out test and the newly formed bone volume on the implant (BV.Im) by bone
      histomorphometry at 2 and 4 weeks after implantation. RESULTS: The bone-implant
      shear strength in the OVX+HA group was significantly lower than that in the
      Sham+HA group at 2 weeks after implantation of the rods. In the OVX+HA+P group,
      the strength was significantly higher than that in the other groups. Similarly,
      at 4 weeks, statistically significant differences were confirmed in the bone
      implant shear strength among the Sham+HA group, the OVX+HA group, and the
      OVX+HA+P group. BV.Im in the OVX+HA group was significantly lower than that in
      the Sham+HA group at 2 weeks after implantation. BV.Im was significantly higher
      in the OVX+HA+P group than that in the OVX+HA group. However, there was no
      difference in BV.Im between the Sham+HA group and the OVX+HA+P group. At 4 weeks
      after implantation, BV.Im was significantly lower in the OVX+HA group than that
      in the other groups, but no difference was found between the Sham+HA group and
      the OVX+HA+P group. CONCLUSIONS: Intermittent administration of PTH has an effect
      to increase new bone formation on the surface of HA-coated implants in the
      osteoporotic condition. This finding suggests that PTH administration is useful
      to improve the initial fixation of HA-coated implants even in osteoporotic
      patients.

PMID- 19089542
TI  - Kinematic analysis of mobile-bearing total knee arthroplasty using a 6-DOF knee
      simulator.
AB  - BACKGROUND: The purpose of this study was to investigate the kinematics of the
      polyethylene insert in two designs of mobilebearing total knee arthroplasty,
      using a six-degrees-of-freedom knee simulator. It was consequently not clear
      whether the motion of the polyethylene bearing in mobile-bearing total knee
      arthroplasty could be demonstrated during the gait cycle or more rapid movement.
      METHODS: A mobile-bearing knee (Zimmer) and a low contact stress rotating
      platform design (Depuy) were mounted on a simulator which was regulated by the
      kinematic data of gait. The simulating test was conducted under a static
      condition as well as under dynamic conditions of 0.5 Hz and 1.0 Hz. We recorded
      the motions of the implants with two charge-coupled device (CCD) cameras, and the
      positions of the insert were calculated. RESULTS: In spite of the same relative
      motion between the femoral component and the tibial tray, the polyethylene insert
      showed unique relative motion according to the given condition. The motion of the
      insert during the dynamic conditions was considerably decreased in comparison to
      the static condition in both mobile-bearing designs. In addition, the insert
      showed a smaller amplitude and frequency of rotations under increasing speed in
      the low contact stress rotating-platform design. The low contact stress rotating
      platform design showed a larger amplitude and frequency of rotations than the
      mobilebearing knee. CONCLUSIONS: Despite the mobility of the insert in the
      mobilebearing total knee arthroplasty, the motion of the insert was decreased
      during dynamic conditions because of the disruption of full contact between the
      femoral component and the polyethylene insert. Differences in the rotation
      between the mobile-bearing knee and the low contact stress rotatingplatform
      design were due to the fixed axis of the internalexternal rotation in the low
      contact stress rotating-platform design. The theoretical advantages for the
      mobile-bearing design over the fixed-bearing design were not demonstrated in this
      study.

PMID- 19089543
TI  - Electron microscopic study on bone formation and bioresorption after implantation
      of beta-tricalcium phosphate in rabbit models.
AB  - BACKGROUND: The role of bone formation and bioresorption in an early stage after
      implantation of beta-tricalcium phosphate (beta-TCP) was investigated using
      scanning and transmission electron microscopy (SEM, TEM). METHODS: The ceramic
      beta-TCP cylinders were implanted into cavities drilled in the femoral condyles
      of eight NZW rabbits. Four of the rabbits were sacrificed at 2 weeks and four at
      4 weeks after implantation, respectively. The femoral condyles were excised to
      prepare the specimens for SEM and TEM. RESULTS: SEM showed giant cells of more
      than 20 mum in diameter were observed on the surface of beta-TCP at 2 weeks after
      implantation. TEM demonstrated that collagen fibrils secreted from the monocytic
      cells invaded beta-TCP micropores at 2 weeks. Multinucleated giant cells (MNGCs)
      were in contact with the surface of beta-TCP at 2 weeks. Some of them had a
      ruffled border (RB) at the cell-substrate interface, characteristic of
      osteoclasts. CONCLUSIONS: These findings suggest that cell-mediated
      disintegration by osteoclasts played a role in the bioresorption of beta-TCP at
      an early stage after implantation. In addition, the micropores of beta-TCP
      ceramic may provide an environment for collagen formation, leading to the
      deposition of apatite crystals. Therefore, the micropores facilitate bone
      ingrowth as well as ceramic resorption.

PMID- 19089544
TI  - Chondrosarcoma of the patella.

PMID- 19089545
TI  - Rapidly destructive arthrosis of the hip joint after insufficiency fracture of
      the acetabulum.

PMID- 19089546
TI  - Myxoinflammatory fibroblastic sarcoma.

PMID- 19089547
TI  - Unilateral stress fracture of the femoral shaft combined with contralateral
      insufficiency fracture of the femoral shaft after bilateral total knee
      arthroplasty.

PMID- 19089549
TI  - Notice of retraction. J Orthop Sci (2008) 13:187-91.

PMID- 19089548
TI  - Iatrogenic calcinosis cutis following extravasation of calcium gluconate.

PMID- 19089550
TI  - Protection against systemic fatal pneumococcal infection by maternal intranasal
      immunization with pneumococcal surface protein A (PspA).
AB  - Streptococcus pneumoniae is a leading causative pathogen responsible for various
      types of bacterial infectious diseases in children. The aim of this study was to
      evaluate the protection conferred against fatal pneumococcal infections during
      infancy by maternal intranasal immunization with pneumococcal surface protein A
      (PspA). Four-week-old female BALB/c mice were immunized with PspA mixed with, or
      without, cholera toxin B (CTB) intranasally twice a week for 3 weeks. After the
      final immunization, they were mated with male mice to obtain offspring. Offspring
      at 10 days old were intraperitoneally inoculated with a pneumococcus strain,
      TIGR4, serotype 4. After the infections their survival periods were monitored.
      Anti-PspA-specific IgG antibody was induced in sera and breast milk at birth and
      maintained for 14 days during nursing periods in the PspA-immunized mother mice.
      At birth, offspring delivered from PspA-immunized mother mice had levels of anti
      PspA-specific IgG antibody in sera same to those in their mothers on the day of
      birth. The survival times to death of offspring delivered from PspA-immunized
      mother mice after systemic fatal pneumococcal infections were significantly
      extended compared to those of controls. These findings suggest that maternal
      intranasal immunization with PspA could be an attractive procedure to employ
      against pneumococcal infections in early childhood.

PMID- 19089551
TI  - Risk factors for central venous catheter-related bloodstream infection: a 1073
      patient study.
AB  - We intended to evaluate the risk factors for catheter-related bloodstream
      infection (CR-BSI) with central venous (CV) catheters. For the hub of the CV
      line, we used three-way stopcocks in the first year of the study and closed
      needleless connectors (NCs) in the second year. Background factors included the
      age and sex of patients; the ward; the specialty service; the CV catheter and its
      days of placement; and the staff compounding the intravenous infusion, i.e.,
      either nurses, who disinfect hands-free, or pharmacists using clean benches.
      Outcome factors included positive culture from the blood-related samples and the
      body temperature estimate. Of a total of 29 221 device-days in 1073 patients,
      positive cultures showed an overall incidence of 2.26 per 1000 device-days.
      Multivariate analysis showed a higher odds ratio of positive cultures for the ICU
      (odds ratio [OR], 4.415; 95% confidence interval [CI], 2.054-9.490]) and for CV
      catheter placement for more than 30 days (OR, 7.529; 95% CI, 4.279-13.247), but
      no significance for male sex (OR, 1.752; 95% CI, 0.984-3.119) or for pharmacists'
      compounding (OR, 2.150; 95% CI, 0.974-4.749). Univariate analysis showed no
      significance for the following factors: age more than 70 years (OR, 0.968; 95% CI
      0.561-1.641), the surgery service (OR, 1.029; 95% CI, 0.582-1.818), double-lumen
      CV catheters (OR, 0.841; 95% CI, 0.465-1.521), or the NC (1.107; 95% CI, 0.673
      1.821). We conclude that the theoretical benefit of the NC, the abolished dead
      space in the hub, contributed little to the outcomes of blood-related culture.
      The hands-free disinfection may have resulted in comparable odds ratios for the
      nurses and the pharmacists compounding the infusions.

PMID- 19089552
TI  - Dissemination of extended-spectrum beta-lactamase-producing Klebsiella pneumoniae
      and Escherichia coli in Thai hospitals.
AB  - Fifty clinical isolates of Klebsiella pneumoniae and Escherichia coli with
      reduced susceptibility to third-generation cephalosporins, collected from 11
      hospitals in Thailand, were studied. All isolates were found to produce extended
      spectrum beta-lactamase (ESBL), as judged by double-disk synergy and combination
      disk methods. Most ESBL-producing K. pneumoniae isolates were resistant to
      ceftazidime (94%) and aztreonam (90%). In contrast, most ESBL-producing E. coli
      isolates were resistant to ceftriaxone (95%) and cefotaxime (74%). Plasmid DNA
      was isolated and beta-lactamase genes were identified by PCR and sequencing. We
      found that SHV-12 and CTX-M-14 were the main ESBLs responsible for resistance in
      K. pneumoniae and E. coli, respectively. SHV-27, SHV-28, and CTX-M-14 were
      detected in three, two, and four K. pneumoniae isolates, respectively. A high
      genetic diversity among ESBL-producing K. pneumoniae and E. coli isolates was
      observed. In addition, the finding of a few isolates that produced identical
      restriction patterns on pulsed field gel electrophoresis (PFGE) suggests the
      clonal spread of resistant bacteria within the hospital.

PMID- 19089553
TI  - Clinical efficacy of azithromycin for male nongonococcal urethritis.
AB  - The aim of this study was to confirm the clinical efficacy of a single-dose
      azithromycin (AZM) regimen (1000 mg) for patients with nongonococcal urethritis
      in real-life practice. The study finally evaluated 55 patients, 42 who were
      symptomatic and 13 who were asymptomatic, after excluding 40 who visited clinics
      only once. Sixteen of the symptomatic patients were diagnosed as having
      nongonococcal chlamydial urethritis, 7 as having nongonococcal nonchlamydial
      urethritis, and 19 as having urethritis without any microbial detection.
      Chlamydia trachomatis was detected in 11 asymptomatic patients, Mycoplasma
      genitalium in 1, and Ureaplasma urealyticum in 1. Of the patients who were
      microbiologically evaluated before and after single-dose AZM, microbiological
      cure was achieved in 87% (20/23) of those with symptomatic nongonococcal
      urethritis and in 100% (13/13) of those with asymptomatic nongonococcal
      urethritis. The clinical cure rate was 86% for the 42 symptomatic patients with
      detectable and undetectable pathogens. There were adverse events in 5 (9%)
      patients but they were commonly mild and self-limited. In conclusion, the single
      dose AZM regimen was well tolerated and eradicated the estimated and potential
      pathogens of nongonococcal urethritis.

PMID- 19089554
TI  - Bacteremia caused by VanC-type enterococci in a university hospital in Japan: a 6
      year survey.
AB  - We retrospectively examined the clinical and microbiological characteristics of
      bacteremia caused by intrinsically vancomycin-resistant (VanC-type) enterococci
      in a university hospital in Japan. Five cases of Enterococcus gallinarum and four
      of Enterococcus casseliflavus bacteremia were identified during the 6 years of
      the survey. Of the nine cases, five were related to neutropenic states with
      hematologic diseases and four were related to biliary tract infection with
      hepatobiliary or pancreatic diseases. VanC-type enterococci were associated with
      12% of all the enterococcal bacteremias, indicating that these species cause
      bacteremia more frequently in Japan than in previously reported areas.

PMID- 19089555
TI  - An outbreak of Pseudomonas aeruginosa infections following thoracic surgeries
      occurring via the contamination of bronchoscopes and an automatic endoscope
      reprocessor.
AB  - An outbreak of Pseudomonas aeruginosa infections occurred after thoracic
      surgeries performed between May and June 2003. Clinical data of seven patients
      were reviewed and the fact was revealed that bronchoscopes were used during
      endotracheal intubation for one-lung ventilation in most patients. P. aeruginosa
      was recovered from the sputum of these patients at a very early stage post
      operation. Environmental samples from bronchoscopes and an automated endoscope
      reprocessor (AER) were cultured and P. aeruginosa strains were recovered from all
      of them. All of these strains were confirmed to be identical by pulsed-field gel
      electrophoresis (PFGE). Inspection of the sterilization cycles of bronchoscopes
      revealed inappropriate management of bronchoscopes and a flaw in the AER; once
      its detergent tank was contaminated, it was not possible to disinfect it. After
      all the bronchoscopes had been disinfected, and the washing machine had been
      remodeled, with the washing process confirmed to be appropriate, the outbreak
      finally ended. This outbreak had two causes, a flaw in the AER and inappropriate
      disinfection procedures. Outbreaks associated with bronchoscopic examinations
      have been reported elsewhere. Bronchoscopes are widely used to facilitate
      endotracheal intubation, especially for one-lung anesthesia. Although they are
      used for only a short time during anesthetic procedures, we should handle them
      more carefully.

PMID- 19089556
TI  - Comprehensive detection of causative pathogens using real-time PCR to diagnose
      pediatric community-acquired pneumonia.
AB  - We have developed a real-time reverse transcription-PCR (RT-PCR) method to detect
      13 respiratory viruses: influenza virus A and B; respiratory syncytial virus
      (RSV) subgroup A and B; parainfluenza virus (PIV) 1, 2, and 3; adenovirus;
      rhinovirus (RV); enterovirus; coronavirus (OC43); human metapneumovirus (hMPV);
      and human bocavirus (HBoV). The new method for detection of these viruses was
      applied simultaneously with real-time PCR for the detection of six bacterial
      pathogens in clinical samples from 1700 pediatric patients with community
      acquired pneumonia (CAP). Of all the patients, 32.5% were suspected to have
      single bacterial infections; 1.9%, multiple bacterial infections; 15.2%,
      coinfections of bacteria and viruses; 25.8%, single viral infections; and 2.1%,
      multiple viral infections. In the remaining 22.6%, the etiology was unknown. The
      breakdown of suspected causative pathogens was as follows: 24.4% were
      Streptococcus pneumoniae, 14.8% were Mycoplasma pneumoniae, 11.3% were
      Haemophilus influenzae, and 1.4% were Chlamydophila pneumoniae. The breakdown of
      viruses was as follows: 14.5% were RV, 9.4% were RSV, 7.4% were hMPV, 7.2% were
      PIV, and 2.9% were HBoV. The new method will contribute to advances in the
      accuracy of diagnosis and should also result in the appropriate use of
      antimicrobials.

PMID- 19089557
TI  - A 12-year-old boy with acute gastroenteritis caused by Edwardsiella tarda O4:H4.
AB  - A 12-year-old boy was brought to the hospital with a 3-week history of watery
      diarrhea mixed with mucus and colicky abdominal pain. Stool culture identified
      Edwardsiella tarda O4: H4, and no other pathogenic bacteria were detected. Acute
      gastroenteritis caused by Edwardsiella tarda O4: H4 was diagnosed. This bacterium
      was shown to be sensitive to ampicillin hydrate. When this antibiotic was
      administered, the condition of the patient improved within a week. The patient
      had a history of eating raw shrimp and fish while traveling with his parents.

PMID- 19089558
TI  - Septic pulmonary embolism caused by Candida albicans after treatment for urinary
      multidrug-resistant Pseudomonas aeruginosa.
AB  - After treatment with antimicrobial chemotherapy for the elimination of urinary
      multidrug-resistant Pseudomonas aeruginosa (MDRP), a 48-year-old man with
      recurrence of bladder cancer complained of acute onset of dyspnea, and computed
      tomography revealed multiple nodular lesions in the lung. Candida albicans was
      isolated from both urinary and blood samples. He was diagnosed as having a septic
      pulmonary embolism caused by C. albicans. Fungal septic pulmonary embolism is a
      rare condition; however, we must be cautious about superinfection as a
      consequence of strong antimicrobial chemotherapy, and understand that the
      treatment for urinary MDRP is likely to be difficult.

PMID- 19089559
TI  - Emergence of the community-acquired methicillin-resistant Staphylococcus aureus
      USA300 clone in Japan.
AB  - We isolated methicillin-resistant Staphylococcus aureus (MRSA) from a 3-month-old
      Indian girl who was born in the United States, moved to Japan, and suffered from
      subcutaneous abscesses in 2007. The MRSA (strain NN36) belonged to multilocus
      sequence type (ST) 8, exhibited agr1, staphylococcal cassette chromosome mec
      (SCCmec) type IVa, and coagulase type III, and was positive for Panton-Valentine
      leukocidin (PVL) and the arginine catabolic mobile element (ACME), just like the
      USA300 clone, which is the predominant community-acquired MRSA (CA-MRSA) in the
      United States. Strain NN36 shared an identical pulsed-field gel electrophoresis
      (PFGE) pattern with the USA300 clone. Although the USA300 clone is of spa1,
      strain NN36 possessed spa985. Strain NN36 was resistant to erythromycin and
      kanamycin, in addition to beta-lactam agents (e.g., oxacillin). The data suggest
      that the USA300 clone has emerged in Japan. Because the USA300 clone has recently
      spread to European countries, surveillance of the USA300 clone should be actively
      performed in Japan.

PMID- 19089560
TI  - Pharyngeal Neisseria gonorrhoeae detection in oral-throat wash specimens of male
      patients with urethritis.
AB  - Detection of Neisseria gonorrhoeae and Chlamydia trachomatis in the pharynx has
      been highlighted in the prevention of the unexpected spread of sexually
      transmitted diseases. We tried to clarify the detection rate of Neisseria
      gonorrhoeae in the pharynx and the clinical relevance of oral-throat wash
      specimens to detect the organism in heterosexual men with gonococcal and
      nongonococcal urethritis. In our cohort of 79 male patients with urethritis, oral
      throat wash specimens were collected after they had gargled with normal saline
      for approximately 30 to 60 s. Positive pharyngeal N. gonorrhoeae was defined as a
      positive result on the strand displacement amplification test for the specimen
      from the oral-throat wash. N. gonorrhoeae was detected in the oral-throat wash
      specimens of 13 (31.7%) of the 41 male patients with gonococcal urethritis. Oral
      throat wash with a nucleic acid amplification test can detect pharyngeal N.
      gonorrhoeae easily and efficiently.

PMID- 19089561
TI  - Comment on "Antimicrobial susceptibility and molecular epidemiological analysis
      of clinical strains of Pseudomonas aeruginosa".

PMID- 19089562
TI  - Current status of anti-vascular endothelial growth factor therapy in Europe.
AB  - Vascular endothelial growth factor (VEGF) is an important modulator of
      angiogenesis, and has been implicated in the pathology of a number of conditions,
      including age-related macular degeneration (AMD), diabetic retinopathy, and
      cancer. AMD is a progressive disease of the macula and the third major cause of
      blindness worldwide. If not treated appropriately, AMD can progress rapidly,
      causing legal blindness within months of the second eye becoming affected. Until
      recently, the treatment options for AMD have been limited, with photodynamic
      therapy (PDT) the mainstay treatment. Although PDT is effective at slowing
      disease progression, it rarely results in improved vision. Pegaptanib and
      ranibizumab are both anti-VEGF therapies licensed for the treatment of
      neovascular AMD in Europe; however, these drugs are not yet available in Japan.
      This article reviews the available clinical data on anti-VEGF therapies for the
      treatment of neovascular AMD in Europe, and considers the future of this exciting
      therapy.

PMID- 19089563
TI  - Two cases of methicillin-resistant Staphylococcus aureus keratitis after Epi
      LASIK.
AB  - BACKGROUND: We describe two severe cases of methicillin-resistant Staphylococcus
      aureus (MRSA) keratitis following Epi-LASIK surgery. CASES: One patient was a 23
      year-old man who underwent Epi-LASIK surgery in both eyes. He developed an
      infectious corneal ulcer in one eye 2 days after surgery and was referred to us 7
      days post-surgery with corneal perforation, for which we performed therapeutic
      penetrating keratoplasty. The other patient was a 32-year-old man who developed
      infectious keratitis in one eye 4 days after bilateral Epi-LASIK and was referred
      to us 2 days later. OBSERVATIONS: Microbial testing revealed MRSA infection as
      the cause of the keratitis in both patients which was successfully treated with
      vancomycin eyedrops. CONCLUSION: Infectious keratitis after refractive surgery is
      uncommon; it is important to diagnose this condition, identify the causative
      agent, and initiate treatment with appropriate antibiotics as soon as possible.

PMID- 19089564
TI  - Ballooning canaliculoplasty after lacrimal trephination in monocanalicular and
      common canalicular obstruction.
AB  - PURPOSE: To evaluate the clinical effect of balloon canaliculoplasty with
      LacriCATH after lacrimal trephination in monocanalicular and common canalicular
      obstruction. METHODS: Silicone intubation following ballooning dilation with a 2
      mm-diameter catheter after lacrimal trephination was attempted in 66 eyes of 62
      patients (10 men, 52 women; mean age, 67.3 years; age range, 34-77 years) with
      epiphora due to monocanalicular or common canalicular obstruction between January
      2003 and February 2005. A total of 56 of the 66 eyes had common canalicular
      obstruction, and ten had monocanalicular obstruction. RESULTS: The cause of
      obstruction in 54 (81.8%) eyes was idiopathic. Overall initial technical
      improvement was achieved in 64 (97.0%) eyes (common canalicular obstruction,
      56/56, 100%; monocanalicular obstruction, 8/10, 80.0%) Immediate clinical
      improvement was achieved in 54 eyes (81.8%). The cumulative patency rates at the
      last clinic visit were 53.6% in cases of common canalicular obstruction and 25.0%
      in cases of monocanalicular obstruction. Causes of failure were combined
      nasolacrimal duct obstruction, recurrent monocanalicular obstruction, and acute
      canaliculitis. CONCLUSIONS: Balloon canaliculoplasty after lacrimal trephination
      is a simple and safe method that may be a good alternative treatment for common
      canalicular and distal canalicular obstructions, before resorting to
      conjunctivodacryorhinostomy with Jones tube insertion.

PMID- 19089565
TI  - Normative database of retinal nerve fiber layer and macular retinal thickness in
      a Thai population.
AB  - PURPOSE: To investigate the distribution of retinal nerve fiber layer (RNFL) and
      macular retinal thickness measured by optical coherence tomography (OCT) in a
      Thai population. METHODS: We studied one eye each of 250 healthy subjects [age >
      or = 18 years; spherical refractive error within +/-6 diopters (D); astigmatism <
      or =3 D; no ocular pathology]. A complete eye examination, standard automated
      perimetry, and fast RNFL and macular thickness measurement by OCT were performed,
      and a disc photograph was taken. The distributions of both thicknesses, including
      their relationship with demographic data, were analyzed. RESULTS: The mean +/- SD
      age of the study population was 44.7 +/- 12.2 years. The mean +/- SD RNFL
      thickness was 109.3 +/- 10.5 m, which was 10% thicker than that in the OCT
      normative database. RNFL decreased 2.3 m per decade (P < 0.001). Sex and
      spherical equivalent were not associated with RNFL thinning. The mean +/- SD
      central foveal thickness was 183.2 +/- 1.3 m. The macular thickness in the outer
      area was significantly thinner than that in the inner area (P < 0.001). The
      temporal regions were the thinnest among the four quadrants (P < 0.001). Thinning
      of all macular areas, except the center, was found to be associated with
      advancing age (P < 0.05). CONCLUSIONS: RNFL thickness in the measured Thai
      population was about 10% thicker than that in the original normative database.
      Macular thickness and RNFL thickness in the superior and inferior quadrants
      decreased with advancing age.

PMID- 19089566
TI  - Recurrence of polypoidal choroidal vasculopathy after photodynamic therapy.
AB  - PURPOSE: To evaluate the recurrence of polypoidal lesions after photodynamic
      therapy (PDT) for polypoidal choroidal vasculopathy (PCV). METHODS: This is a
      retrospective review of data on 28 patients with PCV treated with PDT. The
      recurrent polypoidal lesions were observed with fluorescein and indocyanine green
      angiography. RESULTS: In 26 of the 28 eyes the PCV remained inactive for more
      than 12 months after one to three treatments with PDT. Recurrence of the
      polypoidal lesions after more than a 12-month inactive period was reported in
      eight eyes: three at 15 months, two at 18 months, and three at 21 months. Kaplan
      Meier estimates of recurrence were 11.5% at 15 months, 20.4% at 18 months, and
      38.8% at 21 months, with no subsequent recurrence until passage of 36 months of
      inactivity after the last PDT. Additional PDT after recurrence improved or
      preserved visual acuity in 80% of those treated compared to the visual acuity
      before the first PDT. CONCLUSIONS: Recurrence of PCV occurs in about 40% of eyes
      treated for PCV even after a long period of inactivity, so careful follow-up is
      needed.

PMID- 19089567
TI  - Quantitative PCR for the detection of genomic DNA of Epstein-Barr virus in ocular
      fluids of patients with uveitis.
AB  - PURPOSE: To measure the genomic DNA from Epstein-Barr virus (EBV) in ocular
      fluids and to analyze the clinical relevance of EBV in uveitis. METHODS:
      Intraocular fluids (30 aqueous humor and 30 vitreous fluid samples) were taken
      from 55 patients with uveitis after informed consent was obtained. Samples were
      assayed for EBV DNA using qualitative multiplex polymerase chain reaction (PCR)
      and quantitative real-time PCR. Antibodies to EBV were examined using a
      complement fixation test. RESULTS: EBV DNA was detected in 17 of 60 samples (28%)
      and 16 of 55 patients (29%) using multiplex PCR. However, only three of the 17
      samples showed significantly high copy numbers of EBV DNA with real-time PCR. EBV
      DNA was not detected in the serum of all patients. EBV-specific antibodies were
      positive in the serum of all patients, but not in the vitreous fluid. Vitreous
      anti-EBV antibodies were positive only in patients displaying genomic DNA of EBV
      in the vitreous samples. CONCLUSIONS: EBV DNA was detected by qualitative PCR in
      ocular fluids of many uveitis patients, but only a small proportion of patients
      showed high viral loads on quantitative real-time PCR, indicating that
      replication of the virus takes place only in a few patients.

PMID- 19089568
TI  - Superior segmental optic nerve hypoplasia in youth.
AB  - PURPOSE: The clinical characteristics of superior segmental optic nerve
      hypoplasia (SSOH) in youth were investigated to help establish diagnostic
      criteria. METHODS: Eleven eyes of seven young patients (male/female ratio, 3/4;
      age, 15.1 +/- 3.4 years) who had good visual acuity and inferior visual field
      defects (VFDs) were evaluated. Goldmann and Humphrey perimetries and optic disc
      morphology were analyzed, and the patients were prospectively followed for a long
      period. RESULTS: Visual field defects were wedge shaped and oriented to the blind
      spot, but discontinuous in mild cases. Nerve fiber layer defects (NFLDs) were
      consistent with the VFDs. The optic disc appearance was variable, with double
      ring signs in seven eyes, small discs in three eyes, and an incomplete topless
      disc in one eye. The mothers of none of the patients had gestational diabetes.
      Visual field defects did not progress during the prospective 8.3 +/- 1.3 years
      follow-up. CONCLUSIONS: Characteristic VFD patterns on Goldmann perimetry and
      corresponding NFLDs are important in the diagnosis of SSOH, but not optic disc
      morphology.

PMID- 19089569
TI  - Using frequency-doubling perimetry to detect optic neuropathy in patients with
      Graves' orbitopathy.
AB  - PURPOSE: to test the ability of frequency-doubling technology (FDT) perimetry to
      detect dysthyroid optic neuropathy (DON). METHODS: Fifteen eyes of 15 patients
      with DON and 15 healthy control eyes were studied. Eligible eyes had a diagnosis
      of DON based on visual field abnormalities on standard automated perimetry and
      had visual acuity better than 20/30. FDT testing was performed using both the C
      20-5 screening test and the C-20 full-threshold test. Normal and DON eyes were
      compared with regard to FDT mean sensitivity. RESULTS: Sensitivity ranges were
      40.0%-86.7% for the screening test, and 53.3%-100.0% (total deviation) and 20.0
      93.3 (pattern deviation) for the C-20 threshold test. The corresponding
      specificity ranges were 86.7-100.0, 33.3-93.3, and 26.7-100.0, respectively. The
      best sensitivity/specificity ratios were for one abnormal point depressed <5% in
      the screening test (86.7%/86.7%), one point depressed <1% in the total deviation
      analysis (80.0%/86.7%), and one point depressed <2% in the pattern deviation
      analysis (80.0%/86.7%). DON eyes presented significantly lower than normal
      average sensitivity in the central, pericentral, and peripheral areas.
      CONCLUSIONS: FDT perimetry is a useful screening tool for DON in eyes with normal
      or only slightly reduced visual acuity.

PMID- 19089570
TI  - Color Doppler imaging of the superior ophthalmic vein in different clinical forms
      of Graves' orbitopathy.
AB  - PURPOSE: To compare color Doppler imaging (CDI) parameters of the superior
      ophthalmic vein (SOV) in patients with Graves' orbitopathy (GO) and in normal
      controls. METHODS: Forty-three GO patients and 14 normal controls underwent CDI
      of the SOV. Patients had either fibrotic (lipogenic or myogenic) or congestive
      orbitopathy. The findings for each group were compared. RESULTS: Fifty-eight
      orbits with fibrotic orbitopathy, 28 with congestive orbitopathy, and 28 from
      controls, were studied. In the congestive group, SOV flow was detected in 13,
      undetectable in 11, and reversed in four orbits; in the fibrotic group, it was
      present in 41 and undetectable in 17 orbits. In normal controls, SOV flow was
      detected in 25 and undetectable in three orbits. The differences among the three
      groups were significant. There was also a significant difference between controls
      and the congestive GO orbits but not between the fibrotic group and the other two
      groups. Fibrotic myogenic orbitopathy patients displayed a significantly smaller
      SOV flow than patients with lipogenic orbitopathy. CONCLUSIONS: SOV was
      significantly reduced in orbits with congestive GO or with myogenic fibrotic GO,
      but not in orbits with fibrotic lipogenic orbitopathy. SOV congestion may be a
      contributing pathogenic factor in both congestive and fibrotic myogenic Graves'
      orbitopathy.

PMID- 19089572
TI  - In vivo confocal microscopy of human cornea covered with human amniotic membrane.
AB  - PURPOSE: Amniotic membrane transplantation has been widely performed to
      reconstruct the surface of the eye and treat chemical burns or epithelial
      defects. However, we have difficulty observing the cornea through the opaque
      transplanted amniotic membrane by slit-lamp biomicroscopy. We investigated the
      use of confocal microscopy for observation of human corneas covered with amniotic
      membrane. METHODS: Human amniotic membrane was placed onto the normal corneas of
      five volunteers aged 22-24 years. Then, all layers of the covered corneas were
      observed by in vivo confocal microscopy. RESULTS: Confocal microscopy displayed
      the epithelium, basement membrane, and stroma of the amniotic membrane. It also
      displayed the corneal epithelium. Furthermore, corneal stromal keratocytes and
      the corneal endothelium were clearly observed through the amniotic membrane by
      confocal microscopy. CONCLUSIONS: We demonstrated that in vivo confocal
      microscopy enabled us to observe all layers of corneas covered with amniotic
      membrane in normal human eyes. Our findings suggest that confocal microscopy may
      have advantages for clinical examination of the ocular surface, including all
      layers of the cornea.

PMID- 19089571
TI  - Pharmacokinetic behavior of intravitreal triamcinolone acetonide prepared by a
      hospital pharmacy.
AB  - PURPOSE: We developed a new hospital pharmaceutical preparation of triamcinolone
      acetonide (TA) for intravitreal injections using sodium hyaluronate as the
      vehicle. The purpose of this study was to compare the pharmacokinetic behavior of
      this hospital pharmacy preparation of TA (HPP-TA) to that of a commercial
      preparation of TA (CP-TA) in rats. METHODS: We injected the two preparations of
      TA into the vitreous humor of male Wistar rats. The rats were killed between days
      1 and 21, and the concentration of TA in the vitreous was measured by high
      performance liquid chromatography to determine the pharmacokinetic parameters. We
      also examined the microscopic appearance of the TA particles in these
      preparations. RESULTS: The elimination half-life was 6.08 days for the CP-TA and
      5.78 days for the HPP-TA. A two-compartment model was suitable to approximate the
      pharmacokinetic behavior of HPP-TA in the vitreous body, but this model was not
      suitable for CP-TA, because its pharmacokinetic behavior was not sufficiently
      stable. The particle size of CP-TA was largest, followed by TA powder and HPP-TA.
      Many particles were agglutinated in the CP-TA preparation, whereas the TA
      particles were fine and dispersed in the HPP-TA medium. CONCLUSIONS: The TA
      particle size and the suspension medium are likely important factors in the
      preparation of a safe and stable suspension of TA. HPP-TA satisfied these
      requirements and should be suitable for clinical use.

PMID- 19089574
TI  - Assessing intraocular pressure by rebound tonometer in rats with an air-filled
      anterior chamber.
AB  - PURPOSE: To compare rebound tonometer and cannulation as methods for measuring
      intraocular pressure (IOP) in rats. METHODS: The accuracy of the TonoLab rebound
      tonometer was determined in eight cannulated rat eyes. IOP was manipulated by
      changing air pressure from 20 to 100 mmHg at 10-mmHg intervals, and the IOP was
      measured with the rebound tonometer at each level. The average value of three
      repeated pressure readings was recorded. Correlation analysis and comparison with
      the Bland and Altman method were performed. The intraclass correlation
      coefficient was calculated to assess intraoperator variability. RESULTS: The IOP
      values measured with the TonoLab rebound tonometer were well correlated with the
      actual IOP (r (2) = 0.963, P = 0.01). The mean of the difference between the
      rebound tonometer and actual (cannulation) IOP was 7.41 +/- 7.87%. The intraclass
      correlation coefficient was 0.9, indicating low intraoperator variability.
      CONCLUSIONS: The rebound tonometer showed high accuracy and reliability for IOP
      measurement in rat eyes.

PMID- 19089573
TI  - Correlation of the recurrent FBN1 mutation (c.364C>T) with a unique phenotype in
      a Chinese patient with Marfan syndrome.
AB  - PURPOSE: To describe a Chinese patient with Marfan syndrome who had a unique
      phenotype and a recurrent mutation in the fibrillin-1 (FBN1) gene. CASE AND
      METHODS: A 31-year-old man who had a spontaneous bilateral lens dislocation into
      the vitreous cavity in childhood was found to have retinal and choroidal
      detachments in both eyes. A congenital atrial septal defect was detected. Pars
      plana vitrectomy, lensectomy, and silicone oil tamponade were performed on his
      right eye. Genomic DNA was extracted from leukocytes of peripheral blood, and the
      65 exons and flanking intronic sequences of the FBN1 gene were amplified by
      polymerase chain reaction for mutational screening. RESULTS: A recurrent
      mutation, c.364C>T was detected in exon 4 that resulted in p.Arg122Cys. The
      visual acuity of the right eye improved to 6/60 one year after the surgeries.
      CONCLUSION: DNA screening helps in the diagnosis of Marfan syndrome with unique
      phenotypes. The mutation c.364C>T can be considered to be a hotspot for Marfan
      patients with predominant ectopia lentis.

PMID- 19089575
TI  - Pupillary block in Peters' anomaly.

PMID- 19089576
TI  - Evaluating corneal flap thickness following laser in situ keratomileusis with the
      Moria M2 90-microm single-use-head microkeratome.

PMID- 19089577
TI  - Penicillium endophthalmitis in necrotizing scleritis treated with topical
      corticosteroid and cyclosporin A.

PMID- 19089578
TI  - Early-onset endophthalmitis caused by methicillin-resistant Staphylococcus
      epidermidis after 25-gauge transconjunctival sutureless vitrectomy.

PMID- 19089579
TI  - Severe retinal atrophy due to retinal and choroidal vascular occlusion following
      triamcinolone injection into the nasal mucosa.

PMID- 19089580
TI  - Central retinal vein occlusion in hypertensive patients with chronic hepatitis C
      treated with interferon alpha and ribavirin.

PMID- 19089581
TI  - Optical coherence tomography features of sub-internal limiting membrane
      hemorrhage and temporary premacular cavity following Nd-YAG laser membranotomy in
      Valsalva retinopathy.

PMID- 19089583
TI  - Transient serous retinal detachment after photodynamic therapy for polypoidal
      choroidal vasculopathy.

PMID- 19089582
TI  - Choroidal neovascularization in a patient with ulcerative colitis.

PMID- 19089584
TI  - Patient with Parry-Romberg syndrome complicated by Coats' syndrome.

PMID- 19089585
TI  - Novel virus discovery in field-collected mosquito larvae using an improved system
      for rapid determination of viral RNA sequences (RDV ver4.0).
AB  - In this study, we improved a method for rapid determination of viral RNA
      sequences (RDV) to overcome the limitations of previous versions. The RDV ver4.0
      method can detect RNA sequences with at least 1,000 copies as starting material.
      A novel virus, which was isolated from field-collected Aedes aegypti larvae in
      the Phasi Charoen district of Thailand using C6/36 cells, was identified using
      the RDV ver4.0 protocol. The virus was named Phasi Charoen virus (PhaV). We used
      a high-throughput pyrosequencing approach to obtain more information about the
      genome sequence of PhaV. Analysis of a phylogenic tree based on amino acid
      sequences strongly suggested that PhaV belongs to the family Bunyaviridae.

PMID- 19089586
TI  - Complete nucleotide sequence of the duck plague virus gE gene.

PMID- 19089587
TI  - Mating positions and the evolution of asymmetric insect genitalia.
AB  - Genital asymmetry is a recurring phenomenon in insect morphology and current data
      suggest that it has arisen multiple times independently in several neopteran
      orders. Various explanations have been proposed, including space constraints,
      ecological constraints, sexual selection via antagonistic coevolution, and sexual
      selection via changed mating positions. Each of these hypotheses may best explain
      individual cases, but only the last seems to account for the large majority of
      insect genital asymmetries. Here I summarize the basic assumptions and
      evolutionary steps implied in this model and review the evidence for each of
      them. Several components of this scenario can be easily tested, for example by
      including genital asymmetries and mating positions in phylogenetic analyses.
      Others require in-depth analyses of the function of asymmetric genital
      structures, targeted comparative analyses (e.g., of taxa with sex-role reversal,
      taxa with reversal to symmetry, etc.), and of female genital neuroanatomy.

PMID- 19089588
TI  - Anaerobic degradation of citrate under sulfate reducing and methanogenic
      conditions.
AB  - Citrate is an important component of metal processing effluents such as chemical
      mechanical planarization wastewaters of the semiconductor industry. Citrate can
      serve as an electron donor for sulfate reduction applied to promote the removal
      of metals, and it can also potentially be used by methanogens that coexist in
      anaerobic biofilms. The objective of this study was to evaluate the degradation
      of citrate with sulfate-reducing and methanogenic biofilms. During batch
      bioassays, the citrate, acetate, methane and sulfide concentrations were
      monitored. The results indicate that independent of the biofilm or incubation
      conditions used, citrate was rapidly fermented with specific rates ranging from
      566 to 720 mg chemical oxygen demand (COD) consumed per gram volatile suspended
      solids per day. Acetate was found to be the main fermentation product of citrate
      degradation, which was later degraded completely under either methanogenic or
      sulfate reducing conditions. However, if either sulfate reduction or
      methanogenesis was infeasible due to specific inhibitors (2-bromoethane
      sulfonate), absence of sulfate or lack of adequate microorganisms in the biofilm,
      acetate accumulated to levels accounting for 90-100% of the citrate-COD consumed.
      Based on carbon balances measured in phosphate buffered bioassays, acetate, CO(2)
      and hydrogen are the main products of citrate fermentation, with a molar ratio of
      2:2:1 per mol of citrate, respectively. In bicarbonate buffered bioassays,
      acetogenesis of H(2) and CO(2) increased the yield of acetate. The results taken
      as a whole suggest that in anaerobic biofilm systems, citrate is metabolized via
      the formation of acetate as the main metabolic intermediate prior to
      methanogenesis or sulfate reduction. Sulfate reducing consortia must be enriched
      to utilize acetate as an electron donor in order to utilize the majority of the
      electron-equivalents in citrate.

PMID- 19089589
TI  - Incidence, admission and case-fatality of acute myocardial infarction: weekend
      versus weekday in a Japanese population: 16-year results from Takashima AMI
      Registry (1988-2003).
AB  - For acute myocardial infarction (AMI), "weekend" has been associated with higher
      incidence, admission, and fatality. But, very few studies in this regard are
      available in Japan. Day of the week variation in AMI was examined using an entire
      community covering 16-year AMI registration data from Japan. Data were obtained
      from the Takashima AMI Registry, which covers a stable population of
      approximately 55,000 in central Japan. There were 379 registered first ever AMI
      cases with 121 fatal events within 28 days of onset during 1988-2003. We divided
      the days into two groups: 'Weekend' (Saturday and Sunday) and 'Weekdays' (Monday
      to Friday). The incidence rate (per 100,000 person-year), admission rate (per
      1,000 days) and 28-day case-fatality rates (per 100 events) as well as
      corresponding rate ratios were calculated with 95% confidence intervals. The
      distribution of the day of the week for onset, admission and fatality for all
      subjects was fairly random in our study population; incidence (chi (2) test, P =
      0.8), admission (chi (2) test, P = 0.9) and case-fatality (chi (2) test, P =
      0.8). The incidence, admission, and case-fatality rates were similar for the 2
      day-groups. The incidence rate ratio 1.06 (95% CI: 0.9-1.3), admission ratio 1.03
      (95% CI: 0.8-1.3), and case-fatality ratio 1.18 (95% CI: 0.7-1.9) showed no
      significant risk difference between weekend and weekday. After various
      adjustments, hazard ratio for weekend AMI in reference to weekday AMI was 1.07
      (95% CI: 0.5-2.1). There were no obvious differences in occurrence, hospital
      admission and acute outcome for AMI patients in the weekday or weekend.

PMID- 19089590
TI  - Variation in chemical composition and acaricidal activity against Dermanyssus
      gallinae of four eucalyptus essential oils.
AB  - The results of this study suggest that certain eucalyptus essential oils may be
      of use as an alternative to synthetic acaricides in the management of the poultry
      red mite, Dermanyssus gallinae. At a level of 0.21 mg/cm(2), the essential oil
      from Eucalyptus citriodora achieved 85% mortality in D. gallinae over a 24 h
      exposure period in contact toxicity tests. A further two essential oils from
      different eucalyptus species, namely E. globulus and E. radiata, provided
      significantly (P < 0.05) lower mite mortality (11 and 19%, respectively). Notable
      differences were found between the eucalyptus essential oils regarding their
      chemical compositions. There appeared to be a trend whereby the essential oils
      that were composed of the fewer chemical components were the least lethal to D.
      gallinae. It may therefore be the case that the complexity of an essential oil's
      chemical make up plays an important role in dictating the toxicity of that oil to
      pests such as D. gallinae.

PMID- 19089591
TI  - Evaluation of the poultry red mite, Dermanyssus gallinae (Acari: Dermanyssidae)
      susceptibility to some acaricides in field populations from Italy.
AB  - Red mite field populations from seven naturally infested Italian caged laying
      poultry farms were investigated for their susceptibility to acaricide
      formulations available on the market, containing amitraz, carbaryl and
      permethrin. A minimum of 3,000 mites of all stages were collected from each farm
      and were tested with five acaricide concentrations (5, 10, 20, 50, 100%) plus an
      untreated control (0%). Field red mite populations were found to be tolerant even
      with the highest concentrations with carbaryl and permethrin for six (86%) and
      three (42%) of the investigated farms, respectively (P < 0.05). Furthermore, six
      (86%) of the investigated farms showed a red mite population susceptible to
      amitraz at any concentration. Out of the seven field populations tested with
      amitraz, one population is becoming less tolerant whereas another was the most
      tolerant to carbaryl and permethrin at any concentration. Data show that the lack
      of effectiveness of some acaricides is spreading in Europe and call for the
      adoption of alternative management strategies to avoid development of resistance.

PMID- 19089592
TI  - With those pressures, there have been more cases of plagiarism, scientific fraud
      and misconduct.

PMID- 19089594
TI  - Exploring the relationship between vegetation spectra and eco-geo-environmental
      conditions in karst region, Southwest China.
AB  - Remote sensing of local environmental conditions is not accessible if substrates
      are covered with vegetation. This study explored the relationship between
      vegetation spectra and karst eco-geo-environmental conditions. Hyperspectral
      remote sensing techniques showed that there were significant differences between
      spectral features of vegetation mainly distributed in karst and non-karst
      regions, and combination of 1,300- to 2,500-nm reflectance and 400- to 680-nm
      first-derivative spectra could delineate karst and non-karst vegetation groups.
      Canonical correspondence analysis (CCA) successfully assessed to what extent the
      variation of vegetation spectral features can be explained by associated eco-geo
      environmental variables, and it was found that soil moisture and calcium
      carbonate contents had the most significant effects on vegetation spectral
      features in karst region. Our study indicates that vegetation spectra is tightly
      linked to eco-geo-environmental conditions and CCA is an effective means of
      studying the relationship between vegetation spectral features and eco-geo
      environmental variables. Employing a combination of spectral and spatial
      analysis, it is anticipated that hyperspectral imagery can be used in
      interpreting or mapping eco-geo-environmental conditions covered with vegetation
      in karst region.

PMID- 19089593
TI  - Assessment of pesticide residues in freshwater areas affected by rice paddy
      effluents in Southern Japan.
AB  - Pesticide residues in five freshwater areas that are directly affected by rice
      paddy effluents in southern Japan were measured to determine their maximum
      concentrations and temporal variations. Water samples were collected every week
      during the 2005 rice planting season in Kagoshima Prefecture and stations were
      established in Amori River, Sudo River, Nagaida River (that drains into the
      bigger Kotsuki River), rice paddy drainage canal, and wastewater reservoir (that
      collects effluents from rice paddy fields). Of the 14 target pesticides examined,
      a total of 11 were detected in all stations. Mefenacet, fenobucarb, and
      flutolanil were the three pesticides with the highest maximum concentrations and
      were also detected frequently. Analysis of temporal variations of pesticides
      showed that herbicides had relatively higher concentrations in the earlier stages
      of the rice planting season, while insecticides and fungicides had relatively
      higher concentrations at the later stages. There was no significant difference
      among stations with regards to the temporal patterns of the top three pesticides.
      The calculated toxic units were less than 1 in all stations, implying low or
      negligible environmental risk of pesticides detected to freshwater organisms.

PMID- 19089595
TI  - Analysis of heavy metals in marine fish from Mumbai Docks.
AB  - Seafood containing heavy metals as a result of environmental contamination causes
      toxicity in human beings. To evaluate such kind of contamination, our study
      targeted the analysis of metals such as lead, copper, cadmium, mercury, and
      arsenic in muscle tissue of the fish. The fish commonly consumed such as Brama
      brama (Pomfret), Rachycentron canadus (Surmai/King Fish), Rastrelliger kanagurta
      (Mackerel), Eleutheronema tetradactylum (Ravas/Indian salmon), and Metapenaeus
      monoceros (Brown Prawn) were collected from four different docks in the city. The
      heavy metals in tissue samples of fish were estimated using voltammeter and cold
      vapor atomic absorption spectrophotometer. Heavy metal concentration in the
      tissues varied significantly depending upon the locations from where the fish
      were collected. Although the concentration of arsenic, copper, cadmium, and lead
      were in normal range, the concentration of mercury was found to exceed the daily
      permissible levels (1 microg/g) as a food source for human consumption. We have
      analyzed heavy metals from different locations in Mumbai-Versova dock, Sassoon
      dock, Navi Mumbai dock, and Mazgaon dock.

PMID- 19089596
TI  - Assessment of groundwater quality and hydrogeochemistry of Manimuktha River
      basin, Tamil Nadu, India.
AB  - Groundwater quality assessment study was carried out around Manimuktha river
      basin, Tamil Nadu, India. Twenty six bore well samples were analyzed for
      geochemical variations and quality of groundwater. Four major hydrochemical
      facies (Ca-HCO(3), Na-Cl, Mixed CaNaHCO(3), and mixed CaMgCl) were identified
      using a Piper trilinear diagram. Comparison of geochemical results with World
      Health Organization, United States Environmental Protection Agency, and Indian
      Standard Institution drinking water standards shows that all groundwater samples
      except few are suitable for drinking and irrigation purposes. The major
      groundwater pollutions are nitrate and phosphate ions due to sewage effluents and
      fertilizer applications. The study reveals that the groundwater quality changed
      due to anthropogenic and natural influence such as agricultural, natural
      weathering process.

PMID- 19089597
TI  - Essential fatty acid profiling for routine nutritional assessment unmasks
      adrenoleukodystrophy in an infant with isovaleric acidaemia.
AB  - We report a 16-month-old asymptomatic male with enzyme confirmed isovaleric
      acidaemia (IVA; isovaleryl-CoA dehydrogenase deficiency; OMIM 243500) who, upon
      routine nutritional follow-up, presented evidence of peroxisomal dysfunction. The
      newborn screen (2 days of life) revealed elevated C(5)-carnitine (2.95 MUmol/L;
      cutoff <0.09 MUmol/L) and IVA was subsequently confirmed by metabolic profiling
      and in vitro enzymology. Plasma essential fatty acid (EFA) analysis, assessed to
      evaluate nutritional status during protein restriction and L: -carnitine
      supplementation, revealed elevated C(26:0) (5.0 MUmol/L; normal <1.3).
      Subsequently, metabolic profiling and molecular genetic analysis confirmed X
      linked adrenoleukodystrophy (XALD). Identification of co-inherited XALD with IVA
      in this currently asymptomatic patient holds significant treatment ramifications
      for the proband prior to the onset of neurological sequelae, and critically
      important counselling implications for this family.

PMID- 19089598
TI  - Hsp70 translocates to the nuclei and nucleoli, binds to XRCC1 and PARP-1, and
      protects HeLa cells from single-strand DNA breaks.
AB  - For many years, there has been uncertainty concerning the reason for Hsp70
      translocation to the nucleus and nucleolus. Herein, we propose that Hsp70
      translocates to the nucleus and nucleoli in order to participate in pathways
      related to the protection of the nucleoplasmic DNA or ribosomal DNA from single
      strand breaks. The absence of Hsp70 in HeLa cells, via Hsp70 gene silencing
      (knockdown), indicated the essential role of Hsp70 in DNA integrity. Therefore,
      HeLa Hsp70 depleted cells were very sensitive in heat treatment and their DNA
      breaks were multiple compared to that of control HeLa cells. The molecular
      mechanism with which Hsp70 performs its role at the level of nucleus and
      nucleolus during stress was examined. Hsp70 co-localizes with PARP1 in the
      nucleus/nucleoli as was observed in confocal studies and binds to the BCRT domain
      of PARP1 as was revealed with protein-protein interaction assays. It was also
      found that Hsp70 binds simultaneously to XRCC1 and PARP-1, indicating that Hsp70
      function takes place at the level of DNA repair and possibly at the base excision
      repair system. Making a hypothetical model, we have suggested that Hsp70 is the
      molecule that binds and interrelates with PARP1 creating the repair proteins
      simultaneously, such as XRCC1, at the single-strand DNA breaks. Our data
      partially clarify a previously unrecognized cellular response to heat stress.
      Finally, we can speculate that Hsp70 plays a role in the quality and integrity of
      DNA.

PMID- 19089599
TI  - Silicon-hydroxyapatite bioactive coatings (Si-HA) from diatomaceous earth and
      silica. Study of adhesion and proliferation of osteoblast-like cells.
AB  - The aim of this study consisted on investigating the influence of silicon
      substituted hydroxyapatite (Si-HA) coatings over the human osteoblast-like cell
      line (SaOS-2) behaviour. Diatomaceous earth and silica, together with commercial
      hydroxyapatite were respectively the silicon and HA sources used to produce the
      Si-HA coatings. HA coatings with 0 wt% of silicon were used as control of the
      experiment. Pulsed laser deposition (PLD) was the selected technique to deposit
      the coatings. The Si-HA thin films were characterized by Fourier Transformed
      Infrared Spectroscopy (FTIR) demonstrating the efficient transfer of Si to the HA
      structure. The in vitro cell culture was established to assess the cell
      attachment, proliferation and osteoblastic activity respectively by, Scanning
      Electron Microscopy (SEM), DNA and alkaline phosphatase (ALP) quantification. The
      SEM analysis demonstrated a similar adhesion behaviour of the cells on the tested
      materials and the maintenance of the typical osteoblastic morphology along the
      time of culture. The Si-HA coatings did not evidence any type of cytotoxic
      behaviour when compared with HA coatings. Moreover, both the proliferation rate
      and osteoblastic activity results showed a slightly better performance on the Si
      HA coatings from diatoms than on the Si-HA from silica.

PMID- 19089600
TI  - Investigations on the in vitro bioactivity of swift heavy oxygen ion irradiated
      hydroxyapatite.
AB  - The effect of swift heavy oxygen ion irradiation of hydroxyapatite on its in
      vitro bioactivity was studied. The irradiation experiment was performed using
      oxygen ions at energy of 100 MeV with 1 x 10(12) and 1 x 10(13) ions/cm2 fluence
      range. The irradiated samples were characterized by glancing angle X-ray
      diffraction (GXRD), photoluminescence spectroscopy (PL) and scanning electron
      microscopy (SEM). GXRD showed that irradiated samples exhibited better
      crystallinity. The irradiated samples revealed an increase in PL intensity. In
      addition, the irradiated hydroxyapatite was found to have enhanced bioactivity.

PMID- 19089601
TI  - PEG hydrogels for the controlled release of biomolecules in regenerative
      medicine.
AB  - Polyethylene glycol (PEG) hydrogels are widely used in a variety of biomedical
      applications, including matrices for controlled release of biomolecules and
      scaffolds for regenerative medicine. The design, fabrication, and
      characterization of PEG hydrogels rely on the understanding of fundamental
      gelation kinetics as well as the purpose of the application. This review article
      will focus on different polymerization mechanisms of PEG-based hydrogels and the
      importance of these biocompatible hydrogels in regenerative medicine
      applications. Furthermore, the design criteria that are important in maintaining
      the availability and stability of the biomolecules as well as the mechanisms for
      loading of biomolecules within PEG hydrogels will also be discussed. Finally, we
      overview and provide a perspective on some of the emerging novel design and
      applications of PEG hydrogel systems, including the spatiotemporal-controlled
      delivery of biomolecules, hybrid hydrogels, and PEG hydrogels designed for
      controlled stem cell differentiation.

PMID- 19089602
TI  - Simultaneous determination of glucose and choline based on the intrinsic
      fluorescence of the enzymes.
AB  - It has been possible to perform the simultaneous determination of choline and
      glucose using the intrinsic fluorescence of the corresponding enzyme as an
      analytical signal. This can be done in two ways. First, for low glucose and
      choline concentrations (about 0.55 mM and 0.75 microM respectively) two
      differentiated signals, without mutual interference, are obtained for both
      analytes in the same measurement. Second, when glucose and choline concentrations
      are higher, a new model has been designed which permits the concentrations to be
      accurately determined in samples containing from 0.55 mM to 3.75 mM glucose and
      from 0.75 microM to 11.0 microM choline; the method has been applied to
      simultaneous glucose and choline determinations in serum samples with good
      results. This method gives a better performance than multivariate calibration
      based on Partial Least Squares Regression. The methodology here shown could be
      also used for the simultaneous determination of other pairs of analytes.

PMID- 19089603
TI  - The quality of life of children and adolescents with X-linked agammaglobulinemia.
AB  - INTRODUCTION: The health-related quality of life in X-linked agammaglobulinemia
      was investigated in 25 children and adolescents patients through the Italian
      version of Pediatric Quality of Life Inventory 4.0 Generic Core Scale for
      patients aged less then 18 years, comparing child perception to that of the
      parents and the physician's evaluation. The data were compared with the ones of
      80 healthy controls and the literature data of a group of patients with rheumatic
      diseases. DISCUSSION: The agammaglobulinemia subjects perceived a lower global
      quality of life than the healthy subjects, but significantly higher than the
      rheumatic diseases controls. The clinical relevance of health-related quality of
      life assessment in X-linked agammaglobulinemia pediatric patients is discussed.

PMID- 19089605
TI  - Race, racism and health: disparities, mechanisms, and interventions.
AB  - The goals of this special section are to examine the state-of-the-science
      regarding race/ethnicity and racism as they contribute to health disparities and
      to articulate a research agenda to guide future research. In the first paper,
      Myers presents an integrative theoretical framework for understanding how racism,
      poverty, and other major stressors relate to health through inter-related
      psychosocial and bio-behavioral pathways. Williams and Mohammed review the
      evidence concerning associations between racism and health, addressing the
      multiple levels at which racism can operate and commenting on important
      methodological issues. Klonoff provides a review and update of the literature
      concerning ethnicity-related disparities in healthcare, and addresses factors
      that may contribute to these disparities. Brondolo and colleagues consider racism
      from a stress and coping perspective, and review the literature concerning racial
      identity, anger coping, and social support as potential moderators of the racism
      health association. Finally, Castro and colleagues describe an ecodevelopmental
      model that can serve as an integrative framework to examine multi-level social
      cultural influences on health and health behavior. In aggregate, the special
      section papers address theoretical and methodological issues central to
      understanding the determinants of health disparities, with the aim of providing
      direction for future research critical to developing effective interventions to
      reduce these disparities.

PMID- 19089604
TI  - Immunologic analysis of HIV-uninfected Taiwanese children with BCG-induced
      disease.
AB  - OBJECTIVES: The aim of this study was to evaluate immunity in HIV-uninfected
      children with bacille Calmette-Guerin-induced disease (BCG-ID) over an 8-year
      period, with particular emphasis on underlying diseases. METHODS: Patient
      afflicted with BCG-ID proven by clinical courses, dermatologic features,
      pathology, specific polymerase chain reaction, and/or spoligotyping were enrolled
      between 2000 and 2007. Lymphocyte proliferation, polymorphonuclear function,
      interleukin (IL)-12/23-interferons (IFN)-gamma circuit, and Toll-like receptor 2
      associated signaling were investigated. RESULTS: Of the 271,618 total live births
      who received the BCG vaccine, eight patients (seven males) with BCG-ID were
      enrolled during an 8-year period and presented as three disseminated, two
      distant, and three regional BCG-ID. Their age at onset ranged from 1 to 28
      months. All had a vaccine-injection scar except for one with lower CD3 and
      natural killer cells, compatible with severe combined immunodeficiency (SCID)
      identified by IL-2 receptor common gamma chain (IL2RG) mutation (Arg226Lys). The
      other SCID patient with de novo IL2RG mutation (Trp74Gly) had more recurrent
      infections. The third patient with primary autoimmune neutropenia had
      disseminated BCG-ID extending to abdominal wall. The fourth patient with chronic
      mucocutaneous candidiasis had regional BCG-ID and impaired lymphocyte
      proliferation to Candida and BCG antigens. No defective evidence of
      polymorphonuclear functions, IL-12/23-IFN-gamma circuit, and Toll-like receptor 2
      associated signaling was detected in the remaining four patients. CONCLUSION:
      Immunologic analysis in HIV-uninfected patients with BCG-ID reveals primary
      immunodeficiency diseases, especially in those with deficiencies in T-cell and
      neutrophil functions observed in our cohort, including primary autoimmune
      neutropenia and chronic mucocutaneous candidiasis.

PMID- 19089606
TI  - The interaction of locus of control, self-efficacy, and outcome expectancy in
      relation to HbA1c in medically underserved individuals with type 2 diabetes.
AB  - A common thread among health behavior theories is the importance of perceived
      control, often defined within the health psychology literature as locus of
      control. Inconsistencies have been found regarding the role of locus of control
      in predicting health behaviors. These inconsistencies may be resolved by
      exploring interactions between internal locus of control and other perceived
      control constructs such as self-efficacy and outcome expectancy. The present
      study tested the interaction of internal locus of control, self-efficacy and
      outcome expectancy in relation to HbA1c in patients with Type 2 diabetes. One
      hundred and nine medical patients who were diagnosed with Type 2 diabetes,
      predominantly from an African American as well as disadvantaged background,
      participated in the study. HbA1c was used to indicate gradations of medical
      regimen adherence. A three way interaction among the perceived control measures
      was related to HbA1c. Patients who reported low self-efficacy and low outcome
      expectancy tended to benefit the most from high internal locus of control.
      However, for patients with low self-efficacy and high outcome expectancy, higher
      scores on internal locus of control were related to poorer HbA1c levels. Future
      research examining perceived control constructs may benefit from investigating
      the interacting effects of such variables when evaluating health behaviors.

PMID- 19089607
TI  - Measurement of HIV prevention indicators: a comparison of the PLACE method and a
      household survey in Zambia.
AB  - Reaching populations at greatest risk for acquiring HIV is essential for efforts
      to combat the epidemic. This paper presents, the Priorities for Local AIDS
      Control Efforts (PLACE) method which focuses on understanding the venues where
      people are meeting new sexual partners and behaviors which put people at risk. A
      comparison of data from two PLACE studies in Zambia with a national household
      survey, the Zambia Sexual Behavior Survey 2005, indicated that the PLACE
      population was at greater risk of acquiring HIV. Respondents in the two PLACE
      studies were significantly more likely to report 1+ new partners in the past 4
      weeks, 2+ partners in the past 12 months, 1+ new partner in the past 12 months
      and transactional sex. Data from the PLACE method is important for targeting
      interventions for those most likely to acquire and transmit HIV.

PMID- 19089608
TI  - Lack of association between retrospectively collected pharmacy refill data and
      electronic drug monitoring of antiretroviral adherence.
AB  - Antiretroviral medication refill adherence has not been compared directly to
      electronic drug monitoring (EDM) in any identifiable published study. We
      retrospectively studied adults with undetectable HIV titers on highly active
      antiretroviral therapy. We used Pearson correlation coefficients and receiver
      operating characteristic curves to relate the two adherence measures, and we used
      the Wilcoxon rank-sum test to assess the relation between adherence and viral
      load. In sixty-five subjects, the majority of whom were African American and male
      with median age of 44 years, pharmacy refill adherence was difficult to collect
      retrospectively, was not significantly correlated with EDM adherence, and was not
      significantly related to viral load. Ninety-day supply pharmacy refill adherence
      correctly classified 95% EDM adherence maximally at 94 days between refills, and
      the measure was most sensitive for non-adherence at <90 days. Reassessment of the
      relation between pharmacy refill data and EDM would be warranted when pharmacy
      refill data is collected as soon as feasible from sources with complete data
      capture.

PMID- 19089609
TI  - The presence of bacteria species in semen and sperm quality.
AB  - PURPOSE: To verify the prevalence of semen bacterial contamination and whether
      the contamination could decrease sperm quality. METHODS: Spermiogram, semen
      culture, and sperm transmission electron microscopy (TEM) analysis were
      performed. TEM data were elaborated using a mathematical formula that calculates
      a fertility index (FI)--able to define patients as fertile or infertile--and the
      percentage of sperm apoptosis, immaturity and necrosis. We aligned the amino acid
      sequence of beta-tubulin with protein of the most frequent species isolated from
      semen. RESULTS: Patients were divided according to the contaminating species; in
      each group, we observed fertile individuals, in whom the semen quality was
      similar to that of controls and infertile men whose sperm quality was
      significantly decreased, in terms of motility, FI, apoptosis and necrosis.
      Partial homology between beta-tubulin and bacterial proteins was observed.
      CONCLUSION: Sperm bacterial contamination is quite frequent and could contribute
      to the deterioration of the sperm quality of infertile men.

PMID- 19089610
TI  - Developmental links between trajectories of physical violence, vandalism, theft,
      and alcohol-drug use from childhood to adolescence.
AB  - Differences in developmental trajectories of physical violence, vandalism, theft,
      and alcohol-drug use from ages 10 to 15 were studied. For females and for males,
      three trajectories of theft and of alcohol-drug use increased from 10 years to 15
      years, while only the high trajectory of vandalism increased from ten to 14. All
      trajectories of physical violence decreased. Children who engaged in the high
      trajectories of vandalism, theft, and alcohol-drug use had a high probability of
      also being high in physical violence. Compared to males, females were less likely
      to be on the high trajectory of physical violence, and their trajectories of
      other antisocial behaviors were less strongly associated with high levels of
      physical violence. The results suggest that physical violence during pre
      adolescence and adolescence has a different developmental pattern than other
      forms of antisocial behavior, and that its relation to these other forms of
      antisocial behavior differs by sex.

PMID- 19089611
TI  - Expression and changes of hyperoxidized peroxiredoxins in non-pyramidal and
      polymorphic cells in the gerbil hippocampus during normal aging.
AB  - Oxidative stress is one of predisposing factors to age-related neurodegeneration
      in the brain. In particular, thiol-containing groups are susceptible to oxidative
      stress, which induces the formation of the disulfide bond and/or hyperoxidized
      form of thiol-containing proteins. We observed the protein thiol levels in the
      hippocampal homogenates and also investigated changes in hyperoxidized form of
      peroxiredoxin (Prx-SO(3)) immunoreactivity and proteins levels in the gerbil
      hippocampal subregions during normal aging. Levels of total thiol, non-protein
      thiol, and protein thiol were decreased in the hippocampal homogenates with age.
      At post-natal month 1 (PM 1), pyramidal and non-pyramidal cells in the
      hippocampal CA1 region (CA1) showed Prx-SO(3) immunoreactivity. Prx-SO(3)
      immunoreactivity in the cells was decreased by PM 12, thereafter, Prx-SO(3)
      immunoreactivity in the cells increased again with age. In the CA2/3, Prx-SO(3)
      immunoreactivity in pyramidal cells was not significantly changed; however, the
      immunoreactivity in pyramidal cells was very low at PM 12. Prx-SO(3)
      immunoreactivity in the dentate gyrus (DG) was distinctly changed during aging.
      At PM 1, Prx-SO(3) immunoreactivity in granule and polymorphic cells was weak and
      strong, respectively. The immunoreactivity in the neurons was decreased with age,
      not shown in any neurons at PM 12. Thereafter, Prx-SO(3) immunoreactivity
      increased again with age. In addition, Prx-SO(3) protein level in the hippocampus
      was lowest at PM 12. These results suggest that thiol-containing proteins are
      changed during aging and Prx-SO(3) immunoreactivity was different according to
      cells in the hippocampal subregion during aging.

PMID- 19089612
TI  - The N-glycolyl form of mouse sialyl Lewis X is recognized by selectins but not by
      HECA-452 and FH6 antibodies that were raised against human cells.
AB  - E-, P- and L-selectins critically function in lymphocyte recirculation and
      recruiting leukocytes to inflammatory sites. MECA-79 antibody inhibits L-selectin
      mediated lymphocyte adhesion in several species and does not require sialic acid
      in its epitope. Many other antibodies, however, recognize human selectin ligands
      expressing N-acetylneuraminic acid but not mouse selectin ligands expressing N
      glycolylneuraminic acid, suggesting that difference in sialic acid in sialyl
      Lewis X leads to differential reactivity. We found that HECA-452 and FH6
      monoclonal antibodies bind Chinese hamster ovary (CHO) cells expressing N
      acetylneuraminyl Lewis X oligosaccharide but not its N-glycolyl form. Moreover,
      synthetic N-acetylneuraminyl Lewis X oligosaccharide but not its N-glycolyl
      oligosaccharide inhibited HECA-452 and FH6 binding. By contrast, E-, P- and L
      selectin bound to CHO cells regardless of whether they express N-acetyl or N
      glycolyl form of sialyl Lewis X, showing that selectins have a broader
      recognition capacity than HECA-452 and FH-6 anti-sialyl Lewis x antibodies.

PMID- 19089614
TI  - Special issue in honor of Dr. George H. DeVries.

PMID- 19089613
TI  - From simple toxicological models to prediction of toxic effects in time.
AB  - The ability to predict the effects of toxicants in organisms with reasonable
      accuracy depends to a great extent on the toxico-kinetic models used to describe
      such effects. Toxic effects of organic chemicals and heavy metals have been
      described adequately using a hyperbolic model that considers the concentration of
      the toxicant and the time of exposure only. Such a model relies on the median
      time to effect (ET(50)) of a chemical to estimate effects at any exposure time,
      but cannot make predictions for concentrations other than those tested
      experimentally. A complementary log-to-log model can calculate all ET(50) values
      for a toxicant, thus enabling the hyperbolic model to predict any level of effect
      for any combination of concentrations and times of exposure. The parameter values
      used in both models are obtained from experimental bioassays where the time-to
      effect of a toxicant is recorded regularly in addition to standard acute or
      chronic toxicity data. These models will facilitate the risk assessment of
      chemicals by (1) predicting effects under any combination of time and
      concentrations, and (2) reducing to a minimum the experimental efforts required
      to obtain comprehensive ecotoxicity data.

PMID- 19089615
TI  - Endoscopic findings and clinicopathologic characteristics of ischemic colitis: a
      report of 85 cases.
AB  - Ischemic colitis is the most common type of intestinal ischemia and has a
      clinical spectrum of injury that ranges from mild and transient ischemia to acute
      fulminant colitis. The aim of this study was to explore endoscopic findings and
      clinicopathologic characteristics of ischemic colitis and be accurate enough to
      avoid missed diagnosis or misdiagnosis. A retrospective analysis was undertaken
      of endoscopy findings and clinicopathologic characteristics of 85 cases of
      ischemic colitis from March 2005 to April 2008 in the endoscopy center of our
      hospital. All cases underwent colonoscopy with biopsy within 2 weeks of the onset
      of symptoms, and all specimens with forceps were stained with hematoxylin-eosin
      and observed under light microscopy. Of the 85 cases of ischemic colitis (24 men
      and 61 women, average age 61.36 +/- 14.49 years old, range 29-84), 71 were over
      50 years of age. These cases were associated with the basal diseases such as
      hypertension, cardiovascular disorders, diabetes, and hematological diseases as
      well as a history of abdominal operation. The clinical features usually presented
      with sudden onset of abdominal pain, diarrhea, and hematochezia. Ischemic lesions
      were located mainly in the left colon with segmental form (only descending colon
      affected 16%, only splenic flexure 14%, and only sigmoid colon 23%). The 85
      patients consisted of the non-gangrenous type (82), which were composed of
      reversible IC (76) and chronic IC (6), and the gangrenous type (3). Endoscopic
      appearance of the transient ischemic colitis consisted of petechial hemorrhages,
      edematous and fragile mucosa, segmental erythema, scattered erosion, longitudinal
      ulcerations, and sharply defined segment of involvement. Ischemic colitis of
      stricture was characterized by full-thickness mucosa, lumens stricture, and
      diseased haustrations. The mucosa of gangrenous colitis with cyanotic and
      pseudopolyps was endoscopically observed as well. Clinicopathologic
      characteristics showed mucosal inflammation accompanied by erosion, granulation
      tissue hyperplasia and gland atrophy, lamina propria hemorrhage, and macrophages
      with hemosiderin pigmentation in submucosa in particular. Although endoscopy
      findings and clinicopathologic characteristics of ischemic colitis are
      nonspecific, colonoscopy with biopsy plays a vital role in the early diagnosis of
      ischemic colitis.

PMID- 19089616
TI  - Comparative effects of a high-amylose starch and a fructooligosaccharide on fecal
      bifidobacteria numbers and short-chain fatty acids in pigs fed Bifidobacterium
      animalis.
AB  - Pigs were fed a freeze-dried probiotic (Bifidobacterium animalis CSCC 1941) plus
      a high-amylose maize starch (HAMS) and a fructooligosaccharide (FOS) separately
      or together. Fecal output and total and individual major short-chain fatty acid
      (SCFA) concentrations and excretion were higher and pH was lower with HAMS than
      with FOS relative to when they were fed a low-amylose maize starch (LAMS;
      control). Fecal bifidobacteria numbers and total excretion were equally higher
      during feeding of FOS or HAMS and highest with HAMS + FOS. When probiotic
      supplementation was stopped, bifidobacteria numbers declined rapidly when they
      were fed LAMS, more slowly with FOS or HAMS, and were maintained with HAMS + FOS.
      The data confirm that both HAMS and FOS are prebiotics and suggest that they act
      through different mechanisms and that they are most effective in combination.
      However only HAMS raises fecal SCFA.

PMID- 19089617
TI  - Clinical issues in caring for former chattel slaves.
AB  - Over the centuries, slavery has become embedded into the social fabric of
      Mauritania with generations of abid and bizan (Mauritanian slaves and slave
      masters, respectively) born and raised knowing nothing but the institution of
      chattel slavery. Abid fleeing their station in Mauritania come to the USA with
      unique psychological needs that will affect all of their interactions with the
      medical community. This paper aims to assist health professionals and others
      concerned with the welfare of former chattel slaves in competently serving this
      vulnerable population. Discussion includes an overview of Mauritanian chattel
      slavery, deduced sequelae of chattel slavery, preliminary recommendations for
      mental health and medical treatment protocols, and suggestions for future
      research. A confidential Institutional Review Board (IRB)-approved case report
      will be used to illustrate these objectives.

PMID- 19089618
TI  - CitySongs: primary prevention in the field.
AB  - This case study describes CitySongs, a primary prevention, out-of-school program
      in the inner city that promotes social justice through integrated activities
      aimed at healthy youth development, arts achievement, and community vitality
      through diversity. Key ideas from social science and human service disciplines
      that inform the design and implementation of the program are summarized. The
      authors describe elements of the program's structure and process, as these
      elements enact primary prevention and promote social justice. Finally, program
      impact is discussed as reflected in ongoing staff case notes and in de-identified
      reflective comments from participants, parents, and audience members.

PMID- 19089619
TI  - HTLV-1 Tax protein cooperates with Ras in protecting cells from apoptosis.
AB  - Tax protein of the human T-cell leukemia virus type 1 (HTLV-1) plays a critical
      role in HTLV-I-correlated diseases through its ability to deregulate the
      expression of a vast array of cellular genes. We have previously shown that Tax
      counteracts apoptosis induced by stimuli triggering mitochondria apoptotic
      pathway, most likely by activating CREB-mediated transcription and affecting the
      phosphorylation levels of CREB at Ser-133. Here, we report data that indicate the
      oncoprotein Ras as a possible mediator of Tax-induced apoptosis protection and
      suggest a possible role of Tax in Ras activation. In addition, using inhibitors
      of down stream effectors of Ras, we found that ERK signaling is the most relevant
      for Tax-mediated apoptosis protection. As a whole, our findings provide
      intriguing evidence of a possible link between Ras signaling and Tax capability
      to counteract apoptosis and to enhance P-CREB levels, and implicates a potential
      role for Ras in HTLV-1-induced diseases.

PMID- 19089620
TI  - Cytoskeletal role in differential adhesion patterns of normal fibroblasts and
      breast cancer cells inside silicon microenvironments.
AB  - In this paper we studied differential adhesion of normal human fibroblast cells
      and human breast cancer cells to three dimensional (3-D) isotropic silicon
      microstructures and investigated whether cell cytoskeleton in healthy and
      diseased state results in differential adhesion. The 3-D silicon microstructures
      were formed by a single-mask single-isotropic-etch process. The interaction of
      these two cell lines with the presented microstructures was studied under static
      cell culture conditions. The results show that there is not a significant
      elongation of both cell types attached inside etched microstructures compared to
      flat surfaces. With respect to adhesion, the cancer cells adopt the curved shape
      of 3-D microenvironments while fibroblasts stretch to avoid the curved sidewalls.
      Treatment of fibroblast cells with cytochalasin D changed their adhesion,
      spreading and morphology and caused them act similar to cancer cells inside the 3
      D microstructures. Statistical analysis confirmed that there is a significant
      alteration (P < 0.001) in fibroblast cell morphology and adhesion property after
      adding cytochalasin D. Adding cytochalasin D to cancer cells made these cells
      more rounded while there was not a significant alteration in their adhesion
      properties. The distinct geometry-dependent cell-surface interactions of
      fibroblasts and breast cancer cells are attributed to their different
      cytoskeletal structure; fibroblasts have an organized cytoskeletal structure and
      less deformable while cancer cells deform easily due to their impaired
      cytoskeleton. These 3-D silicon microstructures can be used as a tool to
      investigate cellular activities in a 3-D architecture and compare cytoskeletal
      properties of various cell lines.

PMID- 19089621
TI  - Local drug delivery with a self-contained, programmable, microfluidic system.
AB  - The development and optimization of many new drug therapies requires long-term
      local delivery with controlled, but variable dosage. Current methods for chronic
      drug delivery have limited utility because they either cannot deliver drugs
      locally to a specific organ or tissue, do not permit changes in delivery rate in
      situ, or cannot be used in clinical trials in an untethered, wearable
      configuration. Here, we describe a small, self-contained system for liquid-phase
      drug delivery. This system enables studies lasting several months and infusion
      rates can be programmed and modified remotely. A commercial miniature pump is
      integrated with microfabricated components to generate ultralow flow rates and
      stroke volumes. Solutions are delivered in pulses as small as 370 nL, with pulses
      delivered at any interval of 1 min or longer. A unique feature of the system is
      the ability to infuse and immediately withdraw liquid, resulting in zero net
      volume transfer while compounds are exchanged by mixing and diffusion with
      endogenous fluid. We present in vitro results demonstrating repeatability of the
      delivered pulse volume for nearly 3 months. Furthermore, we present in vivo
      results in an otology application, infusing into the cochlea of a guinea pig a
      glutamate receptor antagonist, which causes localized and reversible changes in
      auditory sensitivity.

PMID- 19089622
TI  - Growth hormone receptor polymorphism and the effects of pegvisomant in
      acromegaly.
AB  - BACKGROUND: Sensitivity to pegvisomant therapy is highly variable in patients
      with acromegaly but determinants of this variability are still unknown. Lack of
      exon 3 (d3-) of the growth hormone (GH) receptor (GHR) has been associated with
      increased biological activity of GH. OBJECTIVE: To assess whether the presence of
      d3-GHR haplotype may have a role in predicting dose regimen and response to
      pegvisomant in acromegaly. DESIGN: Case series. Setting Institutional referral
      center at a tertiary care hospital. Patients Nineteen acromegalic patients with
      active disease after unsuccessful neurosurgery and somatostatin analog therapy.
      MEASUREMENTS: Before and 1, 3, 6 and 12 months after treatment with pegvisomant,
      IGF-I; GH receptor genotype, determined from peripheral blood by polymerase chain
      reaction. All patients started treatment with pegvisomant at 10 mg/daily and then
      increased the dose, according to a fixed schedule, during a 12-month follow-up
      until normalization of IGF-I levels. RESULTS: d3-GHR patients required a
      significant lower dose of pegvisomant and shorter treatment time to normalize IGF
      I. CONCLUSION: The GHR genotype could be useful in predicting dose and individual
      response to pegvisomant in acromegaly.

PMID- 19089623
TI  - State of the cervical section of the spinal cord in patients with remitting
      multiple sclerosis during immunomodulatory treatment.
AB  - MRI scans were obtained of the cervical section of the spinal cords of 30
      patients with remitting multiple sclerosis. During the study period, patients
      received immunomodulatory agents (seven received interferon beta-1a, 13 received
      interferon beta-1b, and 10 received glatiramer acetate). Total focus volume in
      brain matter was assessed before and after treatment, along with the linear size
      of the spinal cord on sagittal sections at the level of the inferior margin of
      the body of C2. There was a significant (p = 0.002) reduction in focus volume in
      the group overall, from 10993 mm(3) (8098-13888 mm(3), p < 0.05; Me = 9336) to
      5630 mm(3) (7400-3860 mm(3), p < 0.05, Me = 4180). There were also significant
      decreases in focus volume on the background of treatment with interferon beta-1b
      and glatiramer acetate (p = 0.026 and 0.027, respectively). Significant
      differences between groups were found in the magnitudes of increases in spinal
      cord atrophy: H (2, n = 30) = 8.06; p = 0.0178. Patients given glatiramer acetate
      showed a significantly smaller increase in atrophy as compared with those treated
      with interferon beta (p < 0.02).

PMID- 19089624
TI  - Pathophysiological aspects of the formation of neurological deficit in multiple
      sclerosis.
AB  - The results of complex studies were used to formulate a concept of the
      development of neurological impairments in multiple sclerosis (MS). Acutely
      developing impairments to spike propagation, reaching the level of conduction
      blockade, due to the active pathological process with demyelinating and axonal
      damage to the CNS lead to the formation of neurological impairments in
      exacerbations of MS, while complete or partial reversion (regression) of these
      symptoms in the stage of remission results from compensatory changes in the
      nature of conduction, which were not, however, accompanied by recovery of
      electrophysiological measures. The development of stable neurological deficit in
      secondary-progressive MS is determined by impairments to spike conduction
      processes associated with significant levels of demyelination and atrophic
      changes in the CNS, with myelin loss and axon death. Finally, the severity of
      cognitive changes is determined by differences in the severities of both the
      focal demyelinating process and diffuse damage to brain substance in MS,
      including the neurodegenerative component. The main factor in transient increases
      in symptoms is the universal lability of electrophysiological parameters,
      including those developing on the background of ion and neurotransmitter
      imbalance.

PMID- 19089625
TI  - The characteristics of motor activity in ISIAH rats in an open field test are
      controlled by genes on chromosomes 2 and 16.
AB  - Quantitative Trait Locus (QTL) analysis was used to identify the loci of
      polygenic characteristics in a study of the genetic determination of the behavior
      of rats with inherited stress-induced arterial hypertension (ISIAH rats).
      Analysis was performed using males of two populations of F2 hybrids (ISIAH x WAG)
      of different ages: 3-4 (n = 106) and six months (n = 130). Chromosomes 2 and 16
      in the young population of F2 rats showed significant associations between two
      characteristics of behavior in ISIAH rats and genetic loci: a) the rats' motor
      activity at the periphery of the open field area with loci in the regions of
      markers D2Rat157-D2Rat88 (LOD score 4.83; p = 0.000058) and D16Rat32 (LOD score
      3.71; p = 0.00023). Together, these two loci accounted for 42.9% of the trait
      variability; b) the rats' motor activity during the first minute of the open
      field test and loci in the region of the marker D16Rat58 (LOD score 3.78; p =
      0.00028). Results obtained by QTL analysis demonstrated a relationship between
      the genetic control of these traits and the animals' age.

PMID- 19089626
TI  - Use of Coaxil (tianeptine) in elderly patients with combined mild cognitive and
      depressive-anxiety disorders.
AB  - The studies reported here addressed 20 patients aged 60-69 years whose clinical
      picture combined the manifestations of mild dementia with those of mild
      depression and anxiety. Patients were treated with Coaxil (tianeptine) for 60
      days at a dose of 37.5 mg/day. Patients were assessed by clinical-psychological
      investigations with addition of the Hamilton scales and neuropsychological
      testing by the Luriya method. Coaxil was found to be highly effective in relation
      to all psychopathological components. Recommendations for the use of Coaxil in
      elderly patients with cognitive and depressive-anxiety disorders are formulated.

PMID- 19089627
TI  - Heterosynaptic potentiation of cholinergic excitatory postsynaptic responses of
      command neurons in the common snail.
AB  - Short-term heterosynaptic potentiation of cholinergic excitatory postsynaptic
      currents and potentials in defensive behavior command neurons was found to be
      evoked by stimulation of the visceral sac in the common snail. It is suggested
      that a mechanism increasing the choline resistance of the postsynaptic zones of
      command neuron membranes is involved in potentiating the excitatory postsynaptic
      responses to sensory stimulation.

PMID- 19089629
TI  - Properties of spreading depression identified by EEG spectral analysis in
      conscious rabbits.
AB  - Reflection of cortical waves of spreading depression in changes in high-frequency
      gamma activity was shown to improve significantly in conditions of bipolar
      recording of brain electrical activity. Intense suppression of the EEG gamma
      range (37-47 Hz) was seen in all cortical areas studied at the moment of onset of
      waves of spreading depression. The drop in the power of EEG gamma activity had
      clear leading and trailing fronts, allowing the passage time of the wave to be
      evaluated in each cortical area, as well as the sequence of propagation. Waves of
      spreading depression were characterized by normal, i.e., sequential movements
      across the cortex, only in the first 3-4 experiments. When experiments were
      continued, there were changes in the latent period and distortions of the
      propagation sequence. In some cases, waves of spreading depression responded to
      standard injections of KCl by developing rapidly (0.5-2 min) over the whole of
      the dorsal surface of the neocortex. More frequently, the wave was delayed (to 6
      9 min) was completely blocked in some areas of the cortex. Different types of
      mild convulsive activity could accompany both the rapid propagation of waves
      across the cortex and inhibition of wave development. In most cases, there were
      no electrophysiological signs of changes in neocortical excitability. However,
      alterations to the spatial characteristics of waves of spreading depression and
      the spontaneous appearance of repeated waves provided evidence of changes in the
      functional state of the brain. Overall, EEG spectral analysis in conscious
      rabbits allowed analysis of spreading depression both in cases of sequential
      propagation across the cortex and in cases of atypical modes of development of
      this phenomenon.

PMID- 19089628
TI  - Natural activation of caspase-3 is required for the development of operant
      behavior in postnatal ontogenesis.
AB  - We have previously demonstrated transient increases in caspase-3 activity in the
      hippocampus of rat pups from age 17 days. We report here our studies on the
      effects of inhibition of caspase-3 during this period on the acquisition of a two
      way avoidance reaction. Rat pups received intracerebroventricular doses of the
      caspase-3 inhibitor Z-DEVD-FMK On postnatal day 18. Control animals of the same
      age received the inactive peptide Z-FA-FMK or isotonic saline solution.
      Inhibition of caspase-3 during the period of its natural activation in the
      hippocampus during early ontogenesis was found to impair the development of
      operant behavior in rats. This was apparent as a reduction in the efficiency of
      learning during acquisition of active avoidance reactions and decreases in the
      numbers of intersignal reactions. Administration of the inhibitor had no specific
      action on the types of conditioned reflex activity less associated with operant
      learning. Thus, there were no differences between the experimental and control
      groups in the numbers of emotional reactions to the conditioned stimulus. The
      number of orientational-investigative conditioned reactions also showed no change
      after administration of Z-DEVD-FMK. On the background of the reduction in the
      efficiency of the acquisition of the conditioned active avoidance reflex, the
      number of incomplete acts, in contrast to other types of conditioned reactions,
      increased significantly after administration of Z-DEVD-FMK, which is evidence for
      the persistence of the ability to form associative connections between activation
      of the conditioned signal and the need to move to the other sector. The
      difficulty in these animals arose at the decision-taking stage on choosing the
      appropriate form of behavior. Changes in orientational-investigative behavior
      were not associated with inhibition of caspase-3 during the critical period of
      development, as the effects of Z-DEVD-FMK and Z-FA-FMK were similar.

PMID- 19089630
TI  - Genotype-dependent characteristics of behavior in mice in cognitive tests. The
      effects of Noopept.
AB  - Male C57BL/6J, BALB/c, and DBA/2J mice showed differences in their abilities to
      perform two cognitive tests. C57BL/6J mice had good learning ability and memory
      trace retention (at 10 days) in a simplified Morris maze, while BALB/c mice had
      low levels of memory trace retention and DBA/2J mice had low learning ability in
      this test. I.p. administration of the nootropic agent Noopept (GVS-111, N
      phenylacetyl-L-prolylglycine ethyl ester) at a dose of 0.5 mg/kg 15 min before
      the start of the test induced significant improvements in long-term memory in
      this test in BALB/c mice but no further improvement in C57BL/6J mice, and had no
      effect in DBA/2J mice. On testing the ability to extrapolate the direction of
      movement of a stimulus, administration of Noopept increased the proportion of
      correct responses in C57BL/6J and BALB/c mice, but had no effect in DBA/2J mice.

PMID- 19089631
TI  - Prestimulus EEG gamma frequencies during formation of a cognitive set to facial
      expressions.
AB  - The power spectra of baseline (prestimulus) EEG recordings from various parts of
      the cortex in the band 1-60 Hz were studied in adult subjects during the stage of
      formation of a cognitive set to facial expressions. Individual variability in the
      power spectra of the baseline EEG, particularly in the gamma range (41-60 Hz)
      made it impossible to average spectra from different subjects. This is the first
      study demonstrating that the EEG at 41-60 Hz was more informative during the
      prestimulus period than recordings at 1-20 Hz and 21-40 Hz. High levels of gamma
      frequency power were found to be dominant in the frontal areas of the right
      hemisphere in groups of subjects with plastic sets; the group of subjects with a
      rigid set showed dominance of gamma-frequency power in the posterior temporal and
      occipital areas of the left hemisphere.

PMID- 19089632
TI  - Behavior-related neuron reactions and the dynamics of neuronal activity.
AB  - The spike activity of neurons with associative functions, studied as a neural
      correlate of behavior, constitutes an efferent spike flow which operates
      continuously throughout each of an animal's actions. However, research practice
      is dominated by methods based on the "stimulus-response" principle. Analysis from
      other points of view, directed to investigating the dynamics of neuron activity
      in monkeys during performance of a multistep behavioral program showed that
      differences in neuron activity of neurons during performance of different
      behavioral actions are not so much in terms of the numbers of cells responding or
      the activation of neurons specialized for the action concerned as in terms of
      changes in the composition of active neurons, with the formation of different
      combinations. As each combination of active neurons determines the distribution
      of efferent signals characteristic of this combination, these data suggest the
      existence of an addressing mechanism encoding efferent signals.

PMID- 19089633
TI  - Morphological changes and manganese content in the brains of rat pups subjected
      to subchronic poisoning with manganese chloride.
AB  - Morphological changes in neurons and the distributions of nerve and glial cells
      were studied, the glial index was calculated, and manganese (Mn) contents were
      determined in the caudate nucleus, the nucleus accumbens, the dorsal and ventral
      septal nuclei, and the frontoparietal areas of the cerebral cortex in the 40-day
      old offspring of rats given different doses (10 and 20 mg/kg) of manganese
      chloride (MnCl2.4H2O) 15-20 days before pregnancy, during pregnancy, and for one
      month after parturition with the first portion of food. Mn poisoning increased Mn
      contents in the brains of rat pups, damaged a small proportion of neurons, and
      produced marked gliosis. These changes are believed to underlie previously
      described impairments to learning processes and emotional state in rat pups.

PMID- 19089634
TI  - Thioredoxin-1 expression levels in rat hippocampal neurons in moderate hypobaric
      hypoxia.
AB  - Previous studies have demonstrated that preconditioning (PC) with three sessions
      of moderate hypoxia significantly increases the expression of the antioxidant
      protein thioredoxin-1 (Trx-1) in the rat hippocampus by 3 h after subsequent
      acute severe hypoxia as compared with non-preconditioned animals. However, it
      remained unclear whether this increase in Trx-1 accumulation during PC is induced
      before severe hypoxia or is a modification of the response to severe hypoxia.
      This question was addressed in the present investigation using experiments on 12
      adult male Wistar rats with studies of Trx-1 expression after PC without
      subsequent severe hypoxia. Immunocytochemical studies were performed 3 and 24 h
      after three episodes of moderate hypobaric hypoxia (three sessions of 2 h at 360
      mmHg with 24-h intervals). Immunoreactivity to Trx-1 24 h after the last session
      was significantly decreased in neurons in all the areas of the hippocampus
      studied (CA1, CA2, CA3, and the dentate gyrus). Immunoreactivity in CA3 was also
      decreased 3 h after hypoxia. These results provide evidence that moderate
      preconditioning hypoxia itself not only does not increase, but even significantly
      decreases Trx-1 expression. Thus, increases in Trx-1 contents in the hippocampus
      of preconditioned animals after severe hypoxia are not associated with the
      accumulation of this protein during PC, but with a PC-induced modification of the
      reaction to severe hypoxia.

PMID- 19089635
TI  - Long-term disorders of behavior in rats induced by administration of tumor
      necrosis factor during early postnatal ontogenesis.
AB  - The proinflammatory cytokine tumor necrosis factor alpha (TNFalpha) is one of the
      main mediators of neuroimmune interactions. Increased production of TNFalpha in
      nerve and immune system cells occurs in infectious diseases, traumas, ischemia,
      and hypoxia. The present study addressed the role of TNFalpha in the formation of
      behavior during early postnatal ontogenesis. TNFalpha was given to rats during
      the third week of life and behavior was tested at ages 1.5 and 3 months using the
      open field test and the elevated plus maze test. Experimental rats differed from
      controls in terms of changes in orientational behavior on testing at 1.5 months
      and an increase in anxiety on testing at 1.5 and 3 months. The different roles of
      proinflammatory cytokines in the brain at the early stages of ontogenesis are
      discussed.

PMID- 19089636
TI  - Caspase-3 activity in hippocampal slices reflects changes in synaptic plasticity.
AB  - Electrophysiological measures of the functional activity of neurons in field CA1
      in conditions of paired-pulse stimulation of Schaffer collaterals were performed
      in relation to the involvement of caspase-3 in mediating neuroplasticity; the
      relationship between functional activity and caspase-3 activity in hippocampal
      slices from Wistar rats was addressed. Enzyme activity was assessed in each
      individual slice at the end of the electrophysiological experiment. The results
      obtained here showed that the highest level of enzyme activity was seen when the
      efficiency of interneuronal interactions decreased. Nerve cell excitability
      showed no changes; interactions increasing synaptic efficiency, particularly in
      paired-pulse stimulation, produced normal response amplitudes. Further
      deterioration of the functional state of slices and impairments in spike
      generation were accompanied by increases in caspase-3 activity to the normal
      level. Increases in the activity of another proteinase, cathepsin B, were
      generally seen in any deviation from normal functioning, though there was no
      correlation with any of the electrophysiological parameters. It is suggested that
      high caspase-3 activity in slices is linked with neuroplastic processes in
      synapses and has no direct relationship to nerve cell apoptosis.

PMID- 19089637
TI  - The role of axonopathy in the mechanisms of development of demyelination
      processes in the central and peripheral nervous system.
AB  - The role of axonopathy in the development of demyelinating processes in the CNS
      and peripheral nervous system was addressed in studies of 43 patients with
      multiple sclerosis (MS) and 144 patients with chronic inflammatory demyelinating
      polyneuropathy (CIDPN). Patients with MS were found to have foci of reduced MRI
      intensity in the T1 regime ("black holes," present in 28%) and regional atrophy
      of the cerebral cortex (in 46%), which showed a significant association with the
      degree of invalidity on the EDSS (Kendall tau = 0.38 and 0.43; p = 0.038 and
      0.021, respectively). The mean fatigue score on the FSS was 4.9 (3.6; 5.4). A
      significant increase in the central conduction time on the background of fatigue
      (p = 0.016), along with an absence of signs of impaired reliability of
      neuromuscular transmission and an absence of past-activation phenomena, suggested
      that central mechanisms were predominant in the formation of fatigue phenomena in
      MS. In addition, 34.9% of patients with MS showed signs of peripheral nervous
      system involvement, while the clinical-electrophysiological pattern in 12.5% of
      patients with CIDPN showed signs of CNS involvement. These data widen existing
      concepts of the mechanisms of formation of axonopathy in the CNS, based on
      evidence for the development of axon-demyelinating processes in CIDPN, which is
      the most accessible model of demyelination for study using contemporary
      neurophysiological methods.

PMID- 19089638
TI  - The influences of cytokines as a possible substrate for the psychological effects
      of immunomodulation therapy in multiple sclerosis.
AB  - Changes in the emotional background make significant contributions to the
      clinical picture of multiple sclerosis (MS), seriously reducing patients' quality
      of life and hindering adaptation during the process of rehabilitation. The
      relationship between mental state and disease activity has been discussed in the
      world literature in recent years and the opinion that mental disorders in MS are
      pathogenetically based is increasingly widespread. The present article discusses
      the potential role of substances mediating immune responses-cytokines-in the
      effects of changes in the functional activity of the nervous system and
      psychoemotional status. The question of their likely involvement in the
      pathogenesis of the side effects of immunomodulatory therapy of MS with beta
      interferons and glatiramer acetate is discussed.

PMID- 19089639
TI  - Characteristics of neurological and cognitive status in patients with multiple
      sclerosis in relation to the location and volumes of demyelination foci and the
      severity of brain atrophy.
AB  - A total of 65 patients with clinically significant diagnoses of remitting
      multiple sclerosis in the stage of remission were studied. Neurological status
      was investigated with assessment on the FS and EDSS scales, with
      neuropsychological testing, and MRI scans (1.5 T). The severity of brain atrophy
      (in terms of the parenchyma volume) and the total volume of foci on T2 images
      were assessed as proportions of intracerebral volume. The severity of
      neurological deficit depended on the volume of intratentorial focal lesions and
      the level of brain atrophy. Cognitive disorders were identified in 89% of
      patients, and the severity of these was associated with the level of atrophy and
      the volume of foci on T2 images in the dominant hemisphere.

PMID- 19089640
TI  - Factors associated with extended length of stay for patients presenting to an
      urban psychiatric emergency service: a case-control study.
AB  - This study assessed factors associated with extended length of stay (ELOS) for
      patients presenting to a psychiatric emergency service (PES). Two hundred six
      subjects with a length of stay of 24 h or longer were compared with time-matched
      controls (patients that presented directly after the ELOS patient). Binary
      logistic regression was used to identify risk factors for ELOS. ELOS was
      associated with suicidal ideation, disposition to an inpatient unit, homicidal
      ideation, lack of insurance, homelessness, male gender, past history of
      psychiatric hospitalization, diagnosis of substance abuse, significant
      psychiatric co-morbidity (represented by three or more Axis I diagnoses), and
      diagnosis of a psychotic disorder. Lack of insurance, suicidal ideation,
      disposition to inpatient unit, and homicidal ideation all made nonredundant
      contributions to predicting stays of 24 h or longer.

PMID- 19089642
TI  - Recovery orientation in hospital and community settings.
AB  - There has been an increasing emphasis on community integration, consumer
      involvement, and recovery-focused treatment; but the extent to which these
      recovery-oriented principles have been adopted in state hospitals is unknown.
      This study surveyed 1,150 staff at three state hospitals and 230 staff at four
      community mental health centers on personal optimism, consumer optimism, and
      agency recovery orientation. Responses were obtained from 729 (63.4%) hospital
      staff and 181 (78.7%) community staff. Staff at state hospitals scored
      significantly lower on all three recovery measures even after controlling for
      background differences. Treatment setting may be an important factor in the
      dissemination of recovery-oriented care principles.

PMID- 19089641
TI  - Substance use, mental illness and violence: the co-occurrence of problem
      behaviors among young adults.
AB  - A paucity of research exists in which the co-occurrence of substance use, mental
      illness, and violence in young adults is examined. Concurrently, there is also a
      lack of research explicating the contribution of theoretically based risk factors
      for these problematic outcomes in this population. This lack of both outcome and
      explanatory research equally affects the utility of theories and interventions
      for this population. This article utilizes a sample of N = 633 21-year-olds to
      examine the prevalence of (1) violence and substance use, (2) mental illness
      (i.e., mood and anxiety disorders) and substance use, and (3) the use of multiple
      substances and investigates the relationship between various social determinants
      and said outcomes. Overall, the prevalence rates for the comorbid conditions were
      low; although on average males had higher rates than did females. Individual
      attitudes, perceived opportunities, and recent stressful life events were
      associated with the co-occurrence of outcomes. Implications for behavioral health
      are explored.

PMID- 19089643
TI  - Release mechanisms behind polysaccharides-based famotidine controlled release
      matrix tablets.
AB  - Polysaccharides, which have been explored to possess gelling properties and a
      wide margin of safety, were used to formulate single-unit floating matrix tablets
      by a direct compression technique. This work has the aim to allow continuous slow
      release of famotidine above its site of absorption. The floating approach was
      achieved by the use of the low density polypropylene foam powder. Polysaccharides
      (kappa-carrageenan, gellan gum, xyloglucan, and pectin) and blends of
      polysaccharides (kappa-carrageenan and gellan gum) and cellulose ethers
      (hydroxypropylmethyl cellulose, hydroxypropylcellulose, sodium carboxymethyl
      cellulose) were tried to modulate the release characteristics. The prepared
      floating tablets were evaluated for their floating behavior, matrix integrity,
      swelling studies, in vitro drug release studies, and kinetic analysis of the
      release data. The differential scanning calorimetry and Fourier transform
      infrared spectroscopy studies revealed that changing the polymer matrix system by
      formulation of polymers blends resulted in formation of molecular interactions
      which may have implications on drug release characteristics. This was obvious
      from the retardation in drug release and change in its mechanistics.

PMID- 19089645
TI  - Analysis of relationship between microbial and methanogenic biomass in methane
      fermentation.
AB  - To analyze the relationship between biomass of microorganisms and methane
      production, the total biomass of bacteria and archaea (BA) during methane
      fermentation was analyzed by the environmental DNA analysis method. In the case
      of using methanogenic sludge as a seed which is generally used for methane
      fermentation, the total BA biomass reached to 1.5 x 10(8) to 3.6 x 10(8) cells/ml
      when methane was produced. On the other hand, soil suspension was used as a seed;
      methane was not produced for 14-day cultivation. However, the total BA biomass
      reached to above 1.5 x 10(8) cells/ml. The methanogen biomass was counted by
      using a fluorescence microscope (coenzyme F420), and the methanogen biomass and
      the ratio of methanogens in the total of BA were analyzed during methane
      fermentation. At the methane-producing phase, the methanogen biomass reached to
      1.3 x 10(8) cells/ml, and the ratio of methanogens was above 70% of the total BA.
      When the ratio of methanogens in a seed was changed, the methane-producing phase
      was moved. However, the relationship between methanogens and other microorganisms
      at the methane-producing phase was almost similar.

PMID- 19089644
TI  - Characterization of cyclodextrin inclusion complexes of the anti-HIV non
      nucleoside reverse transcriptase inhibitor UC781.
AB  - The highly potent anti-HIV agent UC781 is being evaluated for use in topical
      microbicides to prevent HIV transmission. However, UC781 is extremely hydrophobic
      with poor water solubility, a property that may complicate appropriate
      formulation of the drug. In this study, we examined the ability of several
      cyclodextrins, beta-cyclodextrin (beta CD), methyl-beta-cyclodextrin (M beta CD),
      and 2-hydroxylpropyl-beta-cyclodextrin (HP beta CD), to enhance the aqueous
      solubility of UC781. Each of the cyclodextrins provided dramatic increases in
      UC781 aqueous solubility, the order being M beta CD>HP beta CD>beta CD. The
      complexation constants (K (1:1)) of the inclusion complexes were determined via a
      phase solubility technique using high-performance liquid chromatography and
      showed that UC781 solubility increased linearly as a function of cyclodextrin
      concentration. Ultraviolet spectroscopy, Fourier transform infrared spectroscopy,
      differential scanning calorimetry, and 2D (1)H ROESY NMR spectroscopy were used
      to further characterize these UC781/cyclodextrin complexes. The inhibitory
      potency of UC781 and its HP beta CD inclusion complex were evaluated using an in
      vitro HIV-1 reverse transcriptase inhibition assay The inhibitory potency of the
      UC781/HP beta CD complex was 30-fold greater than that of UC781 alone, showing
      that the complexed drug is able to provide substantial inhibition of its target.
      The enhancement of UC781 aqueous solubility is essential for the development of a
      useful vaginal microbicide dosage form, and our data suggest that
      UC781/cyclodextrin inclusion complexes may be useful in this context.

PMID- 19089647
TI  - Biotreatment on cellulose fluff pulp: quaternary ammonium salts finish and
      grafting with beta-cyclodextrin.
AB  - For its potential performances to be expanded, cellulose needs to be processed in
      different ways. Therefore, an object of the present work was to provide a
      chemical modification of cellulose through: a specific finish with two quaternary
      ammonium salts (namely Aliquat 336 and Aliquat 1529, respectively). Chemical
      grafting of beta-cyclodextrin derivative (beta-CD) onto fibers followed by the
      inclusion of benzoic acid in the grafted CD cavities as a probe chemical.
      Physicochemical properties and performances of the untreated and treated fibers
      have been determined with infrared spectra, microscopy, swelling measurements,
      antimicrobial finishing tests, and dye adsorption. Our results show that
      cellulose fibers can be efficiently modified with no significant changes in its
      structural and surface properties; the treated fibers show an attractive behavior
      in swelling, dye adsorption and antibacterial activity.

PMID- 19089646
TI  - Ethanol production from starch hydrolyzates using Zymomonas mobilis and
      glucoamylase entrapped in polyvinylalcohol hydrogel.
AB  - The glucoamylase from Aspergillus niger, immobilized into poly(vinylalcohol)
      hydrogel lens-shaped capsules LentiKats, was used for simultaneous
      saccharification and fermentation (SSF) with Zymomonas mobilis in free form. This
      system was stable in both the repeated batch and continuous mode of SSF. The
      microorganism was found to adsorb on the capsules with immobilized enzyme. This
      increased the ethanol productivity of the repeated batch system with 5% w/v of
      immobilized glucoamylase almost 2.1 times (7.2 g l(-1) h(-1)) compared to free
      enzyme-free microorganism system (3.5 g l(-1) h(-1)). The continuous SSF with the
      immobilized glucoamylase (11.5% w/v) tested for 15 days had productivity 10 g l(
      1) h(-1), which is comparable to continuous experiments on semi-defined glucose
      medium (10 g l(-1) h(-1)). These two systems were stable in both glucoamylase
      activity and microorganism productivity.

PMID- 19089648
TI  - Purification and characterization of pectin lyase produced by Aspergillus
      terricola and its application in retting of natural fibers.
AB  - An indigenously isolated fungal strain identified as Aspergillus terricola with
      assigned fungal strain number MTCC 7588 has been used as source for pectin lyase
      production. The extracellular pectin lyase was purified to homogeneity from the
      culture filtrate of A. terricola by ion exchange and gel filtration
      chromatography. The determined molecular weight was 35 +/- 01 kDa. The K(m) and
      k(cat) (turnover) values of the purified enzyme at 37 degrees C using citrus
      pectin as the substrate were found to be 1.0 mg/ml and 110.0 s(-1), respectively.
      The pH and temperature optima of the enzyme were 8.0 and 50 degrees C,
      respectively. The retting ability of the purified pectin lyase for natural fibers
      viz. Cannabis sativa and Linum usitatissimum has been demonstrated for the first
      time.

PMID- 19089649
TI  - Fifty-gigahertz microwave exposure effect of radiations on rat brain.
AB  - The object of this study is to investigate the effects of 50-GHz microwave
      radiation on the brain of Wistar rats. Male rats of the Wistar strain were used
      in the study. Animals of 60-day age were divided into two groups-group 1, sham
      exposed, and group 2, experimental (microwave-exposed). The rats were housed in a
      temperature-controlled room (25 degrees C) with constant humidity (40-50%) and
      received food and water ad libitum. During exposure, rats were placed in
      Plexiglas cages with drilled ventilation holes and kept in an anechoic chamber.
      The animals were exposed for 2 h a day for 45 days continuously at a power level
      of 0.86 microW/cm(2) with nominal specific absorption rate 8.0 x 10(-4) w/kg.
      After the exposure period, the rats were killed and homogenized, and protein
      kinase C (PKC), DNA double-strand break, and antioxidant enzyme activity
      [superoxides dismutase (SOD), catalase, and glutathione peroxidase (GPx)] were
      estimated in the whole brain. Result shows that the chronic exposure to these
      radiations causes DNA double-strand break (head and tail length, intensity and
      tail migration) and a significant decrease in GPx and SOD activity (p = or<0.05)
      in brain cells, whereas catalase activity shows significant increase in the
      exposed group of brain samples as compared with control (p = or<0.001). In
      addition to these, PKC decreased significantly in whole brain and hippocampus (p
      < 0.05). All data are expressed as mean +/- standard deviation. We conclude that
      these radiations can have a significant effect on the whole brain.

PMID- 19089650
TI  - Optimization of biodiesel production from castor oil using response surface
      methodology.
AB  - The short supply of edible vegetable oils is the limiting factor in the
      progression of biodiesel technology; thus, in this study, we applied response
      surface methodology in order to optimize the reaction factors for biodiesel
      synthesis from inedible castor oil. Specifically, we evaluated the effects of
      multiple parameters and their reciprocal interactions using a five-level three
      factor design. In a total of 20 individual experiments, we optimized the reaction
      temperature, oil-to-methanol molar ratio, and quantity of catalyst. Our model
      equation predicted that the following conditions would generate the maximum
      quantity of castor biodiesel (92 wt.%): a 40-min reaction at 35.5 degrees C, with
      an oil-to-methanol molar ratio of 1:8.24, and a catalyst concentration of 1.45%
      of KOH by weight of castor oil. Subsequent empirical analyses of the biodiesel
      generated under the predicted conditions showed that the model equation
      accurately predicted castor biodiesel yields within the tested ranges. The
      biodiesel produced from castor oil satisfied the relevant quality standards
      without regard to viscosity and cold filter plugging point.

PMID- 19089651
TI  - Application of quartz crystal nanobalance for simultaneous determination of
      vanillylmandelic and homovanillic acids by a net analyte signal-based method.
AB  - Homovanillic acid (HVA) and vanillylmandelic acid (VMA) were selectively
      determined by quartz crystal nanobalance sensor in conjunction with net analyte
      signal (NAS)-based method called HLA/GO. An orthogonal design was applied for the
      formation of calibration and prediction sets including HVA, VMA, and some common
      and structurally similar urine compounds. The selection of the optimal time range
      involved the calculation of the NAS regression plot in any considered time window
      for each test sample. The searching of a region with maximum linearity of NAS
      regression plot (minimum error indicator) and minimum of predicted error sum of
      squares value was carried out by applying a moving window strategy. Based on the
      obtained results, the differences on the adsorption profiles in the time range
      between 1 and 300 s were used to determine mixtures of compounds by HLA/GO
      method. Several figures of merit like selectivity, sensitivity, analytical
      sensitivity, and limit of detection were calculated for both compounds. The
      results showed that the method was successfully applied for the determination of
      VMA and HVA.

PMID- 19089652
TI  - Butanol tolerance in a selection of microorganisms.
AB  - Butanol tolerance is a critical factor affecting the ability of microorganisms to
      generate economically viable quantities of butanol. Current Clostridium strains
      are unable to tolerate greater than 2% 1-butanol thus membrane or gas stripping
      technologies to actively remove butanol during fermentation are advantageous. To
      evaluate the potential of alternative hosts for butanol production, we screened
      24 different microorganisms for their tolerance to butanol. We found that in
      general, a barrier to growth exists between 1% and 2% butanol and few
      microorganisms can tolerate 2% butanol. Strains of Escherichia coli, Zymomonas
      mobilis, and non-Saccharomyces yeasts were unable to surmount the 2% butanol
      growth barrier. Several strains of Saccharomyces cerevisiae exhibit limited
      growth in 2% butanol, while two strains of Lactobacillus were able to tolerate
      and grow in up to 3% butanol.

PMID- 19089653
TI  - Banana as adjunct in beer production: applicability and performance of
      fermentative parameters.
AB  - Traditionally, the raw materials for beer production are barley, hops, water, and
      yeast, but most brewers use also different adjuncts. During the alcoholic
      fermentation, the contribution of aroma compounds from other ingredients to the
      final beer flavor depends on the wort composition, on the yeast strain, and
      mainly on the process conditions. In this context, banana can also be a raw
      material favorable to alcoholic fermentation being rich in carbohydrates and
      minerals and providing low acidity. In this work, the objective was to evaluate
      the performance of wort adjusted with banana juice in different concentrations.
      For this, static fermentations were conducted at 15 degrees C at pilot scale (140
      L of medium). The addition of banana that changed the concentration of all-malt
      wort from 10 degrees P to 12 and 15 degrees P were evaluated ( degrees P is the
      weight of the extract or the sugar equivalent in 100 g solution, at 20 degrees
      C). The results showed an increase in ethanol production, with approximately 0.4
      g/g ethanol yield and 0.6 g/L h volumetric productivity after 84 h of processing
      when concentrated wort was used. Thus, it was concluded that banana can be used
      as an adjunct in brewing methods, helping in the development of new products as
      well as in obtaining concentrated worts.

PMID- 19089654
TI  - Polyethylenimine-based transfection method as a simple and effective way to
      produce recombinant lentiviral vectors.
AB  - HIV-1-derived lentiviral vectors (LvV) are within the most attractive gene
      delivery vehicles in the context of both dividing and quiescent cells. LvV is
      currently produced by the conventional calcium phosphate precipitation method.
      Nevertheless, this procedure is highly susceptible to variations in pH and
      impurities, which lead to inconsistencies in LvV production. Here, we present a
      simple and robust procedure for LvV production using branched 25 kDa
      polyethylenimine, with a transfection efficiency of over 90% and viral titer
      yields of about 1 x 10(7) infective lentiviral particles per milliliter. The
      procedure outlined is simple, consistent, and as inexpensive as the CaPO(4)-based
      method.

PMID- 19089655
TI  - Pituitary adenoma with peliosis: a report of two cases.
AB  - Peliosis is characterised by multiple blood-filled lakes or cavities within
      parenchymatous organs. Typically found in the liver, spleen, bone marrow and
      lymph nodes, it has also been described in other organs such as lungs, kidneys,
      parathyroids and pancreas. The mechanism responsible for the development of
      peliosis remains unknown. (1) A 69 year-old man with a 6-year history of
      acromegaly underwent transsphenoidal surgery for pituitary adenoma. Morphologic
      findings demonstrated a plurimorphous plurihormonal pituitary adenoma consisting
      of somatotrophs, lactotrophs and mammosomatotrophs. The tumor contained several
      blood-filled cavities characteristic of peliosis. (2) A 61-year-old man with a
      prolactin-producing pituitary adenoma who underwent transsphenoidal surgery. In
      the tumor, peliosis was noted. Peliosis in a pituitary adenoma is an intriguing
      finding. The question arises whether it represents vasculogenic mimicry.

PMID- 19089657
TI  - Revisiting Libman-Sacks endocarditis: a historical review and update.
AB  - Libman-Sacks (LS) endocarditis was first described by Libman and Sacks in 1924,
      and is characterized by sterile, verrucous valvular lesions with a predisposition
      for the mitral and aortic valves. It is now regarded as both a cardiac
      manifestation of systemic lupus erythematosus and, in recent years, of the
      antiphospholipid syndrome (APS). Though typically mild and asymptomatic, LS
      endocarditis can lead to significant complications, including severe valvular
      insufficiency requiring surgery, infective endocarditis, and thromboembolic
      events, such as stroke and transient ischemic events. Improvements in imaging
      modalities, particularly in echocardiography, have allowed better estimation of
      the prevalence of the disease, but further investigation is still needed into its
      pathogenesis, treatment, and association with APS.

PMID- 19089656
TI  - A diagnostic approach to adrenal cortical lesions.
AB  - The adrenal gland is not a common specimen in surgical pathology practice as,
      until recently, adrenal tumors were recognized in life only if associated with
      hypersecretion of hormones or evidence of malignancy. However, adrenal nodules
      are not uncommon at autopsy, and the number of these found in life is now
      increasing as they are identified when the abdomen is scanned for the
      investigation of other diseases using computed tomography or magnetic resonance
      imaging. It is therefore becoming increasingly important for the surgical
      pathologist to be aware of the range of pathology in the gland and to understand
      how to approach the specimens. This short review will deal with lesions of the
      adrenal cortex.

PMID- 19089660
TI  - Secretory expression and purification of recombinant Escherichia coli heat-labile
      enterotoxin B subunit and its applications on intranasal vaccination of
      hantavirus.
AB  - In order to further study the B subunit of the Escherichia coli heat-labile
      enterotoxin (LTB), we obtained the LTB gene from pathogenic E. coli, cloned it
      into the pET22b (+) prokaryotic expression vector, and expressed it as a fusion
      protein with His tag in E. coli BL21 (DE3). The recombinant LTB was expressed and
      purified by Ni2+ affinity chromatography. The biological activity of the purified
      recombinant LTB was assayed in a series of monosialotetrahexosylganglioside (GM1)
      ELISA experiments. The recombinant LTB (rLTB) was efficiently expressed under the
      induction of 10 g/l lactose at 37 degrees C for 6 h and yielded up to 31% of the
      total bacterial protein. Fused with pelB signal peptide, rLTB was successfully
      localized to the periplasmic space. GM1-ELISA experiments showed that the rLTB
      obtained retains strong GM1 ganglioside-binding activity. The ELISA result of
      hantavirus nucleoprotein-specific secretory immunoglobulin A (sIgA) and IgG
      showed that intranasal administration of inactivated hantavirus with rLTB
      significantly increased the levels of hantavirus-specific sIgA (P<0.01) and IgG
      (P<0.01) in comparison with inactivated hatavirus alone. In summary, we have
      developed a method for the efficient secretory expression and purification of
      rLTB, and the inactivated hantavirus co-administered intranasally with rLTB could
      effectively induce both mucosal and humoral immune responses specific to
      hantavirus.

PMID- 19089659
TI  - Infections and the antiphospholipid syndrome.
AB  - Currently, the origin of autoimmune diseases is considered to be multifactorial.
      Genetic predisposition, immune system malfunction or even backfire, hormonal
      regulation, and environmental factors, i.e. infections, all play important roles
      in the pathogenesis of autoimmune diseases such as the antiphospholipid syndrome
      (APS). New drugs and strategies aimed at preventing infections could further
      improve the outcome of APS and other autoimmune diseases.

PMID- 19089661
TI  - Outcome of rectal cancer surgery after the introduction of preoperative
      radiotherapy in a low-volume hospital.
AB  - BACKGROUND: The improvement in local control by preoperative radiotherapy for
      rectal cancer can be at the cost of substantial morbidity. AIM OF THE STUDY: The
      aim of this study was to determine the impact of short-course preoperative
      radiotherapy on morbidity and mortality after total mesorectal excision in a low
      volume hospital. METHODS: From 2000 to 2007, 104 patients underwent rectal
      resection for a proven malignancy. Outcome parameters including anastomotic
      leakage rate, duration of hospital stay, and survival were retrospectively
      compared between patients who received radiotherapy followed by resection and
      patients who underwent resection alone. RESULTS: Anastomotic leakage occurred in
      11 of 28 patients (39%) who underwent radiotherapy and in 10 of 54 patients (19%)
      in the surgery-alone group (P = 0.04). The length of hospital stay was
      significantly longer in the radiotherapy group in comparison with the surgery
      alone group (median 22 vs. 12 days; P = 0.002). Independent predictors of
      decreased overall survival were high American Society of Anesthesiologists
      classification, application of preoperative radiotherapy, necessity of Intensive
      Care Unit admission, and advanced pathological stage. CONCLUSIONS: A negative
      impact of preoperative radiotherapy on morbidity and mortality after rectal
      cancer surgery with an annual caseload of 16 was observed. Auditing of local
      practices is essential for quality control and potential improvement of clinical
      outcome.

PMID- 19089662
TI  - CA 19-9 and survival in advanced and unresectable pancreatic adenocarcinoma and
      cholangiocarcinoma.
AB  - BACKGROUND: The CA 19-9 tumour marker is increasingly used to monitor response to
      therapy in patients with pancreatic adenocarcinoma. Serum CA 19-9 levels have
      also been shown to correlate with survival. However, their role in
      cholangiocarcinoma is less clear. AIM OF STUDY: To assess the utility of CA 19-9
      levels in the management of patients with advanced pancreatic adenocarcinoma or
      cholangiocarcinoma in routine clinical practice is the aim of the study. METHODS:
      A retrospective analysis of CA 19-9 values and survival was performed in 26
      patients with pancreatic adenocarcinoma receiving gemcitabine and in 18 patients
      with cholangiocarcinoma. RESULTS: Patients with advanced pancreatic
      adenocarcinoma receiving gemcitabine who experienced a decrease of > or = 20% in
      CA 19-9 concentration had a median survival of 13.9+ months (range 4.2-23.5)
      compared to 7.6+ months (range 4.0-14.7) in those without such a change (p =
      0.0109). In patients with advanced cholangiocarcinoma, the median survival was
      longest in those with a baseline CA 19-9 level of less than 1,000 U/ml; 11.8
      months (range 1.0-41.4) vs 6.2 months (range 3.1-9.4; p = 0.0075). CONCLUSIONS:
      The CA 19-9 concentration has a valuable role in predicting outcome in patients
      with pancreatic adenocarcinoma and cholangiocarcinoma. It is helpful in guiding
      therapy and should be used accordingly in oncology practice.

PMID- 19089663
TI  - Inflammatory myofibroblastic tumor of mesentery: a case report.
AB  - INTRODUCTION: Inflammatory myofibroblastic tumor occurring at intra-abdominal
      sites in children has rarely been described. In the abdomen, mesentery is a rare
      location for an inflammatory myofibroblastic tumor. CASE REPORT: A case report of
      inflammatory myofibroblastic tumor of mesentery presenting as painless abdominal
      swelling is presented. Histopathological study of specimen documented the
      diagnosis. Complete resection of tumor was done with no recurrence seen in follow
      up.

PMID- 19089664
TI  - Risk of other cancers in individuals with a family history of pancreas cancer.
AB  - BACKGROUND: Inherited predisposition to pancreas cancer accounts for
      approximately 10% of cases. Familial aggregation may be influenced by shared
      environmental factors and shared genes. We evaluate whether a family history of
      pancreas cancer is a risk factor for ten specified cancers in first-degree
      relatives: bladder, breast, colon, head and neck, lung, lymphoma, melanoma,
      ovary, pancreas, and prostate. METHODS: Risk factor data and cancer family
      history were obtained for 1,816 first-degree relatives of pancreas cancer case
      probands (n = 247) and 3,157 first-degree relatives of control probands (n =
      420). Unconditional logistic regression models using generalized estimating
      equations were used to estimate odds ratios (ORs), and 95% confidence intervals
      of having a first-degree relative a specified cancer. RESULTS: A family history
      of pancreas cancer was associated with a doubled risk of lymphoma (OR = 2.83, 95%
      CI = 1.02-7.86) and ovarian cancer (OR = 2.25, 95% CI = 0.77-6.60) among
      relatives after adjustment. Relatives with a family history of early-onset
      pancreas cancer in a proband had a sevenfold increased risk of lymphoma (OR =
      7.31, 95% CI = 1.45 to 36.7). Relatives who ever smoked and had a family history
      of pancreas cancer had a fivefold increased risk of ovarian cancer (OR = 4.89,
      95% CI = 1.16-20.6). CONCLUSION: Family history assessment of cancer risk should
      include all cancers. Assessment of other known and suspected risk factors in
      relatives will improve risk evaluation. As screening and surveillance methods are
      developed, identifying those at highest risk is crucial for a successful
      screening program.

PMID- 19089665
TI  - Mucinous cystadenoma arising in an isolated ileal duplication cyst.
AB  - INTRODUCTION: A 64-year-old woman with a 2-year history of bilateral breast
      carcinoma with axillary node metastasis and chemotherapy was admitted to our
      hospital due to tumor attached to the ileum, discovered during the routine
      control examination. DISCUSSION: Computerized axial tomography showed oval cystic
      tumor in terminal ileum that measured 7 cm in the largest diameter and shared
      peritoneal coat with small intestine and was filled with dense fluid. Tumor
      abutted intestine but did not communicate with intestinal lumen. The surgical
      procedure was simple because cyst was attached to the antimesenteric side of the
      terminal ileum and did not communicate with the adjacent intestine.
      Pathohistological examination showed mucinous cystadenoma with high-grade
      epithelial dysplasia in the isolated ileal duplication cyst. The presence of
      epithelial dysplasia found in duplication cyst suggested potential to undergo
      malignant transformation. CONCLUSION: In conclusion, we report a unique case of
      mucinous cystadenoma arising in isolated ileal duplication cyst. This case report
      expands the potential range of clinical variability of alimentary tract
      duplications. Surgical removal of alimentary tract duplication in patients
      without symptoms is also recommended because many potential complications or even
      malignant transformation may result from these anomalies.

PMID- 19089666
TI  - Umbilical metastasis or Sister Mary Joseph's nodule as a very early sign of an
      occult cecal adenocarcinoma.
AB  - Umbilical metastasis (Sister Mary Joseph's nodule) is a rare occurrence and
      indicates, in most of the patients, an advanced intraabdominal malignancy. It may
      be the first sign of an underlying adenocarcinoma, originating mainly from the
      gastrointestinal or genitourinary tract. An extremely rare case of a Sister Mary
      Joseph's nodule is described herein, where the metastatic umbilical nodule was
      the first sign of a cecal adenocarcinoma and became evident 8 months before the
      onset of the disease. Diagnostic evaluation and surgical management are discussed
      along with a review of the literature. This case is presented in order to
      emphasize the need for thorough investigation of any umbilical lesion especially
      in elderly patients.

PMID- 19089667
TI  - Putative auto-infarct of a pancreatic gastrinoma: a case report.

PMID- 19089668
TI  - Carney's triad: case report and review.
AB  - INTRODUCTION: Carney's triad is a rare pathogenic entity which consists of the
      association in young women of multiple condromatosis in the lung, gastric
      leiomyosarcoma, and extradrenal paraganglioma; although the presence of three at
      the same time is not required for its diagnosis. CASE REPORT: We present the case
      of a 27-year-old woman who was diagnosed of pulmonary multiple hamartomatosis and
      gastric stromal tumor. DISCUSSION: A review of the literature shows the most
      important prognosis factors and therapeutic options. Surgery for gastrointestinal
      stromal tumors and extradrenal paraganglioma seems to be the best treatment up to
      date.

PMID- 19089669
TI  - Appendiceal mucocele. a retrospective analysis of 19 cases.
AB  - BACKGROUND: Appendiceal mucocele is an infrequent well-recognized entity that can
      present in a variety of clinical syndromes or can be asymptomatic and discovered
      incidentally. PATIENTS AND METHODS: Nineteen patients with a diagnosis of primary
      appendiceal mucocele treated in our institution between January 1, 1987 and
      December 31, 2006 were included in this retrospective analysis. RESULTS: The
      histological examination of the specimens revealed simple and hyperplastic
      appendiceal mucocele in nine cases (47%), mucinous appendiceal cystadenoma in
      eight cases (42%), and mucinous appendiceal cystadenocarcinoma in two cases
      (11%). Thirteen patients (68%) underwent appendectomy, five patients (26%) right
      colectomy, and two patients (6%) underwent right colectomy for invasive
      appendiceal cystadenocarcinoma and at the same time right nephrectomy and
      sigmoidectomy, respectively, for concomitant malignancy. CONCLUSION: Mucocele of
      the appendix may be related to a benign or malignant appendiceal process, leading
      to individualized diagnosis and treatment.

PMID- 19089670
TI  - Relative rates of missed diagnosis for colonoscopy, barium enema, and flexible
      sigmoidoscopy in 379 patients with colorectal cancer.
AB  - BACKGROUND: Failures of diagnosis of colorectal cancer by colonoscopy, barium
      enema, and flexible sigmoidoscopy have been demonstrated using various
      techniques. A relative assessment of these diagnostic tests for patients with
      colorectal cancer has not been reported. This study was designed to determine
      relative rates of failures for these tests when applied to diagnosis of
      colorectal cancer. METHODS: We created a database of patients with colorectal
      cancer diagnosed between 2000 and 2005. Records were reviewed for the results of
      colonoscopy, barium enema, and flexible sigmoidoscopy in the 3 years prior to
      diagnosis. An examination that was negative for cancer with no immediate follow
      up was defined as a failure of diagnosis, either from inaccurate observation,
      failure to examine the entire colon, or failure of timely follow-up. The failure
      rates were compared. RESULTS: Three hundred seventy-nine patients, who had 421
      examinations, were analyzed. The diagnosis of colorectal cancer failed in 60 of
      379 patients (16%). These 60 patients had 71 examinations that failed to make the
      diagnosis: 25 of 282 colonoscopies (9%), 16 of 79 barium enemas (20%), and 30 of
      60 flexible sigmoidoscopies (50%). These differences were statistically
      significant. CONCLUSIONS: Failure rates for colonoscopy, barium enema, and
      flexible sigmoidoscopy were 9%, 20%, and 50%.

PMID- 19089671
TI  - Effective palliation of advanced cholangiocarcinoma with sorafenib: a two-patient
      case report.
AB  - BACKGROUND: Cholangiocarcinoma is a relatively rare invasive carcinoma that
      arises from the lining of the gallbladder and bile ducts and carries a very poor
      prognosis (Chabner BA et al. Harrison's manual of oncology. New York: McGraw
      Hill; 2008). Its incidence in the US is on average one case per 100,000 persons
      per year and may be increasing in frequency (Darwin PE. Cholangiocarcinoma [Web
      page]. emedicine from WebMD, http://www.emedicine.com/med/TOPIC343.HTM , accessed
      July 22, 2008). Currently, the only treatment option that offers a potential for
      cure is radical surgical resection. Typically, only 30% of patients qualify for
      this, while, for the remainder, treatment is only palliative (Chabner BA et al.
      Harrison's manual of oncology. New York: McGraw-Hill; 2008). Sorafenib is an oral
      targeted agent that acts as a multikinase inhibitor and competitively inhibits
      the Raf, vascular endothelial growth factor receptor 2 (VEGFR2), VEGFR3, platelet
      derived growth factor receptor beta, Flt3, and C-KIT receptors (Chabner BA et al.
      Harrison's manual of oncology. New York: McGraw-Hill; 2008). It has demonstrated
      effective clinical antitumor activity in both renal cell and inoperable
      hepatocellular carcinoma gaining Food and Drug Administration approval for the
      latter carcinoma in November 2007. Its role in advanced cholangiocarcinoma is yet
      to be defined. METHODS: Two female patients with biopsy-proven multifocal
      moderately differentiated cholangiocarcinoma received single-agent sorafenib at
      standard doses. RESULTS: Both patients derived benefit in the form of disease
      stabilization with negligible cancer-related side effects lasting 4+ months.
      Sorafenib side effects were relatively modest aside for rash in one patient.
      CONCLUSIONS: Sorafenib use resulted in effective palliation in two patients with
      advanced cholangiocarcinoma. Larger phase 2 trials, will be necessary to confirm
      this initial observation.

PMID- 19089672
TI  - A rare cause of distal bile duct stenosis.
AB  - INTRODUCTION: In a patient with a distal bile duct stenosis a definite diagnosis
      could not be made preoperatively. DISCUSSION: The histologic evaluation of the
      surgical resection specimen revealed infiltration of the pancreatic head and the
      distal bile duct by breast tumor cells. CONCLUSION: The metastasis was the only
      tumor manifestation after mastectomy 12 years ago.

PMID- 19089673
TI  - Symptomatic therapies in multiple sclerosis. Introduction.

PMID- 19089674
TI  - Vesicourethral dysfunction in multiple sclerosis. Initial assessment based on
      lower urinary tract symptoms and their pathophysiology.
AB  - The most common lower urinary tract symptoms (LUTS) in multiple sclerosis (MS)
      are irritative, obstructive or mixed (association of irritative and obstructive
      LUTS). Generally irritative LUTS are typical in patients with cortical, brainstem
      or mild spinal cord lesions; obstructive symptoms are frequent in patients with
      spinal cord lesions (below the pontine micturition centre) or at the level of the
      sacral micturition centre. Irritative LUTS are often associated with detrusor
      overactivity, whereas obstructive LUTS are associated with detrusor sphincter
      dyssynergia or detrusor areflexia/hypocontractility. Proper management of these
      LUTS often could be planned without specialised assessment, in accordance with
      the algorithms proposed by International Consultation on Incontinence.

PMID- 19089675
TI  - Diagnosis and therapy for neurogenic bladder dysfunctions in multiple sclerosis
      patients.
AB  - Neurogenic lower urinary tract dysfunctions are common in patients with multiple
      sclerosis and for most of them urinary dysfunction has the most negative impact
      on their social life. No correlation exists between clinical urinary symptoms and
      urodynamic patterns. Abnormal urodynamic patterns may be present in asymptomatic
      patients. Both clinical and urodynamic findings may change during the course of
      the illness. Early diagnostic approach and scheduled follow-ups are mandatory in
      order to prevent upper urinary tract complications and improve quality of life
      (QoL).

PMID- 19089676
TI  - Management of bladder dysfunction in multiple sclerosis patients: the nurse's
      point of view.
AB  - It is estimated that as many as 90% of people with multiple sclerosis (MS)
      experience some type of urinary disturbance over the course of the disease. The
      importance of an interdisciplinary approach is crucial in the management of a
      symptom requiring the involvement of different professionals, with specific
      expertise in evaluation and treatment. The MS nurse is perhaps the professional
      most likely to be in a position to initiate the process of identifying urological
      dysfunction. The evaluation can be started by reviewing symptoms recorded in the
      patient's medical records over time. Along with the use of a urinary diary and a
      check of the patient's post-void residual at the time of each visit, this can aid
      the MS nurse in recognising which urinary dysfunction could be affecting the
      patient. The MS nurse can also have an important role in teaching the patient
      behaviour strategies that aid in both evaluating and treating urinary
      dysfunction. Finally, the MS nurse can be the primary instructor of techniques
      related to intermittent catheterisation procedures. A new topic highlighting the
      ever-developing role of the MS nurse is in the field of rehabilitation. This
      article highlights urinary symptoms experienced by people with MS and strategies
      used for treating them. The role of the MS nurse in managing urinary dysfunction
      is also discussed.

PMID- 19089677
TI  - Dysphagia in multiple sclerosis: from pathogenesis to diagnosis.
AB  - Abnormalities of swallowing are commonly encountered in Multiple Sclerosis (MS),
      especially in the most disabled patients. The disturbances usually involve oral
      and pharyngeal phases of swallowing, although upper oesophageal sphincter
      dysfunction has also been detected. MS patients need to be effectively evaluated
      and managed in order to recognize dysphagia before any medical complications such
      as aspiration pneumonia appear. An integrated approach is proposed to define the
      severity of dysphagia and to devise the most appropriate
      therapeutic/rehabilitative methodology.

PMID- 19089678
TI  - Management of dysphagia in patients affected by multiple sclerosis: state of the
      art.
AB  - Dysphagia in multiple sclerosis (MS) has been found to be far more frequent than
      expected, and should be considered a dangerous condition from its onset because
      of its potentially serious complications. Among the several classification
      scales, we use the "O'Neil severity graduation scale" for its correlation between
      investigation imaging and patients' symptoms. In this paper we describe our
      treatment plans of mild, moderate and severe dysphagia following a preliminary
      assessment of symptoms carried out according to the O'Neil dysphagia graduation
      scale.

PMID- 19089679
TI  - Nutritional assessment and malnutrition in multiple sclerosis.
AB  - Malnutrition is often identified in patients in chronic diseases and dysphagia is
      the major contributing factor. The evaluation of the nutritional status included
      assessment of the swallowing abilities, food intake and lifestyle. Weight is the
      first parameter for suspecting a malnutrition, it is considered significant when
      weight loss major that 10% of normal weight occurs over a period of six months.
      The objective of evaluating the nutritional status of the patient is to identify
      metabolic alteration that may influence nutritional status. Hematological
      parameters and the assessment of type and quantities of food consumed are the
      first step of clinical approach. A number of questionnaires, such as Subjective
      Global assessment, Mini nutritional assessment or Malnutritional Universal
      screening tool, have been developed in order to score the level of malnutrition.
      Caloric needs can be easily calculated using formula for catabolism or protein
      and water needs and intake. Finally is crucial to underline the importance of
      multidisciplinary assessment.

PMID- 19089680
TI  - Age-related changes in the use of study context to increase recollection.
AB  - We examined how context presented at study affects recollection of words in
      younger and older adults. In Experiment 1, participants studied words presented
      with a picture of a face (context-rich condition) or a rectangle (context-weak
      condition), and subsequently made 'Remember', 'Know', or 'New' judgments to words
      presented alone. Younger, but not older, adults showed higher Remember accuracy
      following rich- than weak-context trials. In Experiment 2, we manipulated the
      type of processing engaged during the encoding of context-word pairs. Younger and
      older adults studied words presented with a picture of a face under a surface
      feature (gender) or binding feature (match) instruction condition. Both age
      groups showed higher Remember accuracy in the binding than surface instruction
      condition. Results suggest that providing rich contextual detail at encoding
      boosts later item recollection in younger adults. Older adults, however, do not
      spontaneously engage in the processes required to boost recollection, though
      instructional manipulation during encoding lessens this deficit.

PMID- 19089681
TI  - Neuropsychological deficits in relation to symptoms of ADHD: independent
      contributions and interactions.
AB  - The aim of the present study was to investigate possible independent and combined
      effects of inhibitory control, delay aversion, and RT variability in relation to
      symptoms of hyperactivity/impulsivity and inattention. A community-based sample
      of school children (N = 111) completed neuropsychological tasks designed to
      measure inhibitory control, delay aversion, and RT variability. Behavioral
      symptoms were measured through parental and teacher ratings of the DSM-IV
      criteria for ADHD and ODD. The results showed that inhibitory control and RT
      variability were primarily related to symptoms of inattention rather than
      hyperactivity/impulsivity. Further, out of the three neuropsychological factors
      studied, only inhibitory control contributed uniquely to the variance of ADHD
      symptoms. However, significant interaction effects of delay aversion and RT
      variability on symptoms of both hyperactivity/impulsivity and inattention were
      found. This study shows the importance of searching for possible combined effects
      of neuropsychological factors to learn more about the different pathways that
      lead to ADHD symptoms in children.

PMID- 19089682
TI  - Myocardial material parameter estimation: a comparison of invariant based
      orthotropic constitutive equations.
AB  - This study investigated a number of invariant based orthotropic and transversely
      isotropic constitutive equations for their suitability to fit three-dimensional
      simple shear mechanics data of passive myocardial tissue. A number of orthotropic
      laws based on Green strain components and one microstructurally based law have
      previously been investigated to fit experimental measurements of stress-strain
      behaviour. Here we extend this investigation to include several recently proposed
      functional forms, i.e. invariant based orthotropic and transversely isotropic
      constitutive relations. These laws were compared on the basis of (i) 'goodness of
      fit': how well they fit a set of six shear deformation tests, (ii) 'variability':
      how well determined the material parameters are over the range of experiments.
      These criteria were utilised to discuss the advantages and disadvantages of the
      constitutive laws. It was found that a specific form of the polyconvex type as
      well as the exponential Fung-type law from the previous study were most suitable
      for modelling the orthotropic behaviour of myocardium under simple shear.

PMID- 19089683
TI  - Biomechanical evaluation of porous biodegradable scaffolds for revision knee
      arthroplasty.
AB  - Tibial bone defect is a critical problem for revision knee arthroplasty. Instead
      of using metallic spacer or cement, biodegradable scaffolds could be an
      alternative solution. A numerical model of a revision knee arthroplasty was thus
      developed to estimate the mechanical resistance of the scaffold in this demanding
      situation. The tibia, scaffold, and prosthesis were represented by simplified
      parameterised geometries. The maximal gait cycle force was applied asymmetrically
      to simulate a critical loading. Several parameters were analysed: 1) inter
      individual variability, 2) cortical bone stiffness, 3) cortical bone thickness,
      4) prosthesis fixation quality, and 5) scaffold thickness. The calculated
      scaffold strain was compared to its experimental ultimate strain. Among the
      tested parameters, failure was only predicted with scaffold thickness below 5 mm.
      This study suggests that biodegradable bone scaffolds could be used to fill bone
      defects in revision knee arthroplasty, but scaffold size seems to be the limiting
      factor.

PMID- 19089685
TI  - How do mesenchymal stromal cells exert their therapeutic benefit?
AB  - In recent years mesenchymal stromal cells (MSC) have emerged as a major new form
      of cell therapy. While the original perception was that MSC were stem/progenitor
      cells with the potential to contribute to the regeneration of tissue, more recent
      data suggest that the principal mechanism of MSC activity is through the release
      of soluble mediators that elicit the observed biologic response. Future studies
      are needed to identify more completely the spectrum of therapeutic applications
      and delineate better the associated molecular and cellular mechanisms.

PMID- 19089686
TI  - Natural killer cell immunotherapy for cancer: a new hope.
AB  - Recently there has been a substantial gain in our understanding of the role NK
      cells play in mediating innate host immune responses. Although NK cells have long
      been known to mediate antigen independent tumor cytotoxicity, the therapeutic
      potential of NK cell-based immunotherapy has yet to be realized. Manipulating the
      balance between inhibitory and activating NK receptor signals, sensitization of
      tumor target cells to NK cell-mediated apoptosis, and recent discoveries in NK
      cell receptor biology have fueled translational research that has led to clinical
      trials investigating a number of novel methods to potentiate NK cytotoxicity
      against human malignancies.

PMID- 19089684
TI  - RNA under attack: cellular handling of RNA damage.
AB  - Damage to RNA from ultraviolet light, oxidation, chlorination, nitration, and
      akylation can include chemical modifications to nucleobases as well as RNA-RNA
      and RNA-protein crosslinking. In vitro studies have described a range of possible
      damage products, some of which are supported as physiologically relevant by in
      vivo observations in normal growth, stress conditions, or disease states. Damage
      to both messenger RNA and noncoding RNA may have functional consequences, and
      work has begun to elucidate the role of RNA turnover pathways and specific damage
      recognition pathways in clearing cells of these damaged RNAs.

PMID- 19089687
TI  - Slow release of growth factors and thrombospondin-1 in Choukroun's platelet-rich
      fibrin (PRF): a gold standard to achieve for all surgical platelet concentrates
      technologies.
AB  - Platelet concentrates for surgical topical applications are nowadays often used,
      but quantification of the long-term growth factor release from these preparations
      in most cases is impossible. Indeed, in most protocols, platelets are massively
      activated and there is no significant fibrin matrix to support growth factor
      release and cell migration. Choukroun's platelet-rich fibrin (PRF), a second
      generation platelet concentrate, is a leucocyte- and platelet-rich fibrin
      biomaterial. Here, we show that this dense fibrin membrane releases high
      quantities of three main growth factors (Transforming Growth Factor b-1 (TGFbeta
      1), platelet derived growth factor AB, PDGF-AB; vascular endothelial growth
      factor, VEGF) and an important coagulation matricellular glycoprotein
      (thrombospondin-1, TSP-1) during 7 days. Moreover, the comparison between the
      final released amounts and the initial content of the membrane (after forcible
      extraction) allows us to consider that the leucocytes trapped in the fibrin
      matrix continue to produce high quantities of TGFbeta-1 and VEGF during the whole
      experimental time.

PMID- 19089688
TI  - Delivery of testosterone to the brain by intranasal administration: comparison to
      intravenous testosterone.
AB  - Intranasal (i.n.) administration has emerged as a strategy to deliver
      therapeutics to the brain. Here, we compared i.n. and intravenous (i.v.)
      administration for testosterone. About 75% of the i.n. administered testosterone
      entered the blood. However, whole brain levels of testosterone were about twice
      as high after i.n. administration as after i.v. administration. About two-thirds
      of the testosterone entering the brain after i.n. administration did so by direct
      entry by nasal routes and the remainder indirectly by first entering the blood
      and then crossing the blood-brain barrier. All brain regions except the frontal
      cortex had higher levels of testosterone after i.n. administration than after
      i.v. administration, although the differences among brain regions varied much
      more for the i.n. route. The olfactory bulb, hypothalamus, striatum, and
      hippocampus had the highest levels after i.n. administration. The brain uptake
      pattern suggested a variety of distribution routes likely involving the
      cerebrospinal fluid, diffusion through brain tissue, and transport through nerve
      projections. Regional distribution patterns were similar after either i.n. or
      i.v. administration, suggesting that the dominant factor determining
      distribution/retention was the same for either route of administration. We
      conclude that the i.n. administration route delivers testosterone systemically
      and can target the brain, especially the olfactory bulb, hypothalamus, striatum,
      and hippocampus.

PMID- 19089689
TI  - A two-component drug delivery system using Her-2-targeting thermosensitive
      liposomes.
AB  - We report on a new method for enhancing the specificity of drug delivery for
      tumor cells, using thermosensitive immunoliposomes. The liposomes are conjugated
      to the antibody trastuzumab (Herceptin), which targets the human epidermal growth
      factor receptor 2 (Her-2), a cell membrane receptor overexpressed in many human
      cancers. Being thermosensitive, the liposomes only release their contents when
      heated slightly above body temperature, allowing for the possibility of tissue
      targeting through localized hyperthermia. Using self-quenching calcein, we
      demonstrate the release of liposome contents into cell endosomes after brief
      heating to 42 degrees C. To further increase targeting specificity, we
      incorporate the concept of a two-component delivery system that requires the
      interaction of two different liposomes within the same endosome for cytoplasmic
      delivery. Experimental evaluation of the technique using fluorescently labeled
      liposomes shows that a two-component delivery system, combined with intracellular
      disruption of liposomes by hyperthermia, significantly increases specificity for
      Her-2-overexpressing tumor cells.

PMID- 19089690
TI  - Inhibitory effect of small interfering RNA specific for a novel candidate target
      in PB1 gene of influenza A virus.
AB  - Influenza, mainly caused by influenza virus, is becoming one of the major
      concerns in the world. Limitation in vaccines necessitates the urgent development
      of new therapeutic options against this virus. In the present study, we designed
      small interfering RNA (siRNA) targeting overlapping gene of PB1 and PB1-F2 gene
      of the influenza A virus and investigated its effect against influenza A virus
      infection. A reduction in virus-associated cell apoptosis was observed in A549
      cells treated with this siRNA. Furthermore, its antiviral effect was confirmed by
      different methods. Also, a marked decrease of virus titer in chicken embryos
      treated with the siRNA was observed. The findings of this work highlight the
      potential of this shared region to be an additional therapeutic target for the
      treatment of influenza virus infection.

PMID- 19089691
TI  - Antileishmanial activity, pharmacokinetics and tissue distribution studies of
      mannose-grafted amphotericin B lipid nanospheres.
AB  - Leishmania parasite resides mainly in the liver and the spleen and multiplies.
      Effective therapy of leishmaniasis could be achieved by delivering
      antileishmanial drugs to these sites. Present investigations were aimed at
      developing lipid nanospheres of amphotericin B (LN-A) anchored with mannose to
      achieve targeted delivery to the liver. Mannose is specifically involved in the
      recognition of parasite or appropriate ligands on the macrophage surface LN-A,
      and mannose-anchored lipid nanospheres (LN-A-MAN) were prepared by homogenization
      followed by ultrasonication method. Particle size and zeta potential were
      measured using Malvern Zetasizer. The average particle size after sterilization
      of LN-A and LN-A-MAN ranged from 193.4 +/- 1.1 to 775.8 +/- 9.1. Leishmaniasis
      was induced in BALB/c mice by injecting Leishmania donovani parasites
      intravenously. Infected mice were administered with a single dose (5 mg/kg body
      weight) of LN-A, LN-A-MAN, and Fungizone (marketed product).The efficacy of the
      formulations was evaluated by measuring the reduction in parasite burden.
      Fungizone reduced 82 and 69%, LN-A reduced 90 and 85%, LN-A-MAN reduced 95 and
      94% of parasite burden in the liver and the spleen, respectively. LN-A and LN-A
      MAN-treated mice did not show any elevation in serum glutamate pyruvate
      transaminase (SGPT), alkaline phosphatase (ALP), urea, and creatinine levels as
      compared with Fungizone. Pharmacokinetic parameters were estimated and the
      concentration of amphotericin B (AmB) in mice plasma declined biexponentially and
      AmB concentrations were significantly higher for LN-A- and LN-A-MAN than
      Fungizone-treated mice (P < 0.05). Tissue distribution patterns were studied in
      different tissues such as the liver, the spleen, the kidney, and the brain of
      BALB/c mice. LN-A-MAN was found to distribute more rapidly to the liver and the
      spleen explaining the reason for higher antileishmanial activity.

PMID- 19089692
TI  - Fluorodeoxyglucose positron emission tomography (FDG-PET) and PET/computed
      tomography imaging characteristics of thyroid lymphoma and their potential
      clinical utility.
AB  - BACKGROUND: A relative paucity of data exists in the literature with regard to
      the utility of fluorodeoxyglucose positron emission tomography (FDG-PET) imaging
      in the clinical management of patients with primary lymphoma of the thyroid gland
      (PTL). PURPOSE: To explore the FDG-PET imaging characteristics and their
      potential role in PTL, and to compare the results with anatomical imaging
      modalities. MATERIAL AND METHODS: Patients with thyroid lymphoma who had
      undergone whole-body FDG-PET or PET/computed tomography (CT) during their course
      of the disease were identified by examination of case records. PET scans were
      reevaluated, and maximum standardized uptake value (SUV(max)) was calculated and
      used as the semiquantitative measure of FDG uptake for this analysis. CT and/or
      magnetic resonance imaging (MRI) studies carried out within 1 week of FDG-PET
      scan and without any therapeutic intervention between the two studies were
      considered for the purpose of comparison. A total of six patients with 20 studies
      (14 FDG-PET and six PET/CT examinations) were identified following the criteria.
      All patients were female (age 16-83 years). Among these, five were proven to have
      PTL. Two patients had localized PTL (stage IE), two patients had associated
      regional nodal involvement (IIE), and one patient had associated nodal
      involvement on both sides of the diaphragm (IIIE) at presentation. Except for one
      patient with follicular B-cell lymphoma, all others were diffuse large-B-cell
      lymphoma (DLBCL) subtype. RESULTS: Avid FDG uptake was observed in both cases of
      untreated PTL, with SUV(max) of 23 and 7.6, respectively. One patient showed
      focal FDG uptake (SUV(max) 6.7) in the thyroid in the setting of a responding
      abdominal non-Hodgkin lymphoma (NHL) and was subsequently proven as adenomatous
      nodule with Hurthle cell changes. Following successful therapy, SUV(max) declined
      consistently with improvement in disease status. In one patient, complete
      response was noted earlier by FDG-PET compared to CT. Disease recurrence was
      detected earlier by FDG-PET compared to CT in two patients with increased FDG
      activity in both thyroid lobes without any corresponding CT abnormality.
      CONCLUSION: FDG-PET is a useful and sensitive modality for assessing disease
      activity in thyroid lymphoma. Its ability to detect disease recurrence was found
      to be superior compared to CT in two patients.

PMID- 19089693
TI  - Atherosclerotic plaque development and instability: a dual role for VEGF.
AB  - Vascular endothelial growth factor (VEGF), a potent growth factor for endothelial
      cells and inducer of angiogenesis, is important for endothelial integrity and
      thus for vascular function. On the other hand, VEGF may enhance the
      pathophysiologic mechanism of plaque formation and plaque destabilization. In
      this review we discuss the data available so far for VEGF as angiogenic and/or
      inflammatory cytokine in the vulnerable atherosclerotic plaque.

PMID- 19089694
TI  - Tissue distribution of haemolytic Gallibacterium anatis isolates in laying birds
      with reproductive disorders.
AB  - Gallibacterium anatis biovar haemolytica has been suggested to have a causal role
      in peritonitis and salpingitis in chickens. Therefore, the aim of this study was
      to investigate the occurrence of G. anatis biovar haemolytica in chickens with
      reproductive disorders. One hundred and forty one birds from 31 layer flocks were
      submitted for necropsy and the following organs were examined for bacteria:
      choana, trachea, lung, heart, liver, spleen, ovary, oviduct, duodenum and cloaca.
      Examination for Escherichia coli was included as it can induce reproductive
      disorders. G. anatis was isolated in pure culture from the reproductive tract of
      affected birds in six of the 31 flocks while E. coli was obtained in pure culture
      from 10 of them. Both G. anatis and E. coli were isolated from the reproductive
      tract of 14 of the 31 flocks. The genetic diversity of the Gallibacterium
      isolates was assessed by amplified fragment length polymorphism on a subset of 83
      isolates. Generally, each flock was infected with a single clone, which could be
      isolated from various sites in the birds. However, in two flocks, the majority of
      birds yielded positive samples from the internal organs, indicating that these
      particular clones may be more invasive. The findings support previous suggestions
      that G. anatis biovar haemolytica is associated with infection of the
      reproductive tract of chickens, making it a likely cause of lowered productivity
      and an animal welfare concern.

PMID- 19089695
TI  - Executive functioning in children and adolescents with Major Depressive Disorder.
AB  - The present investigation examined neurocognitive functioning, focusing on
      executive functioning (EF), in 39 children and adolescents with Major Depressive
      Disorder (MDD) and 24 healthy control subjects all ages 8 to 17 years. The
      Wechsler Intelligence Scale for Children-Third Edition along with several
      measures of executive functioning including the Wisconsin Card Sorting Task,
      Trail Making Test, Controlled Oral Word Association Test, and the Stroop Color
      Word Test were administered. The neurocognitive profiles for the group of
      depressed children and adolescents were grossly intact as most scores on
      intellectual and EF measures fell within the average range and did not differ
      from the comparison group. Mental processing speed was decreased in the MDD
      versus normal control group and 27% of the depressed group performed below
      average on the Trail Making Test. This investigation provided a good base from
      which to compare future literature on EF in outpatients with early-onset MDD.

PMID- 19089697
TI  - Antidepressant direct-to-consumer advertising and social perception of the
      prevalence of depression: application of the availability heuristic.
AB  - This study examined the effect of antidepressant direct-to-consumer advertising
      (DTCA) on perceived prevalence of depression. A survey of Midwestern residents
      showed that those with high recall for antidepressant DTCA tended to estimate the
      prevalence of depression higher than those with low ad recall. However, with a
      source-priming cue before their estimation, the significant association was
      eliminated. Results indicate that people use antidepressant DTCA as a basis for
      their judgment of the prevalence of depression in normal situations where the
      veracity of information is not highlighted.

PMID- 19089699
TI  - Evaluating the educational potential of health PSAs with preschoolers.
AB  - Children learn from a variety of televised programs, including the short public
      service announcements (PSAs) that air between children's programs. PSAs are
      designed to repetitively expose children to important content ranging from the
      benefits of reading to health-related messages. The purpose of this study was to
      evaluate 5 PSAs containing health messages for preschoolers (i.e., nutrition,
      physical activity, and hand washing). Using an experimental framework, we
      examined children's ability to learn the messages and transfer that knowledge and
      apply it in novel situations. Child PSA viewers were able to recall more of the
      educational content, apply this knowledge to specific choices contained in each
      message, and transfer this knowledge to novel situations compared with their
      nonviewing counterparts. Implications are discussed.

PMID- 19089698
TI  - Models of health and models of interaction in the practitioner-client
      relationship in acupuncture.
AB  - The doctor-patient relationship has been widely studied in biomedicine. However,
      little research has focused on similar provider-client relationships in holistic
      healthcare forms. Based on ethnographic research with acupuncture clients and
      practitioners, the authors found that participants used specific models of health
      to understand and develop subsequent models of interaction, and in doing so,
      provided a clear critique of biomedicine. This article offers a brief overview of
      major models of healthcare, including biomedical, biopsychosocial, and holistic.
      The authors present current models of interaction that have been used to
      understand the biomedical doctor-patient relationship, and discuss the utility of
      both sets of models as they relate to the ethnographic observations. Although a
      particular model of health (biomedical or holistic) does not necessitate a
      particular model of health interaction (paternalism, consumerism, or
      collaboration), participants' attempts to tie these 2 realms together are
      important to understanding practitioner-patient relationships in all healthcare
      situations.

PMID- 19089700
TI  - Moderating roles of primary social influences in the relationship between
      adolescent self-reported exposure to antismoking messages and smoking intention.
AB  - This study explores moderating roles of primary social influences in the
      relationship between adolescent triers' and experimenters' self-reported exposure
      to antismoking messages and their smoking intentions. The theoretical arguments
      are drawn from primary socialization theory, group socialization theory, and the
      social development model, and the data are from the 2004 National Youth Tobacco
      Survey. The tobit regression models demonstrate that, as a primary social
      influence, peer smoking seems to be a strong risk factor for all of the
      adolescent segments' smoking intentions, whereas parental monitoring can be a
      significant counter-risk factor for middle-schoolers' smoking intentions. In
      addition, school intervention programs and parental monitoring against smoking
      appear to play a moderating role in the relationship between high-school triers'
      self-reported exposure to antismoking messages and their smoking intentions. The
      findings seem to suggest that campaigners should make more efforts to incorporate
      primary social influences to prevent adolescent smoking. The findings also
      suggest that campaigners should tailor antismoking programs to fit specific
      target audiences. In particular, middle-school experimenters deserve more
      attention from antismoking campaigners because they seem most vulnerable to
      future smoking.

PMID- 19089701
TI  - Patients' reasons for refraining from discussing internet health information with
      their healthcare providers.
AB  - This exploratory study examined factors that constrain patients from discussing
      Internet health information with their healthcare providers. Participants (N =
      714) were asked to list reasons why they have not talked with their providers
      about Internet health information they had found. Factors (N = 767) included
      patient attributions about the information, systems or circumstances, fear of
      treading on the provider's turf, face-saving concerns, and patient perceptions of
      provider attributions about the information. Comparisons between those who had
      and those who had not talked to their healthcare providers about their Internet
      research revealed significant differences in types of constraining factors
      indicated. Issues concerning an increasingly Internet-savvy public and provider
      patient relationships are considered in the discussion within the framework of
      the goals, planning, action theory. Continued efforts in provider and patient
      education can help to overcome barriers that restrict communication concerning
      Internet health research.

PMID- 19089702
TI  - Locating relationship and communication issues among stressors associated with
      breast cancer.
AB  - This article clarifies how the social contexts in which breast cancer survivors
      live can contribute to the stress they experience because of the disease. Guided
      by Solomon and Knobloch's (2004) relational turbulence model and Petronio's
      (2002) communication privacy management theory, this study explores personal
      relationship and communication boundary issues within stressors that are
      associated with the diagnosis, treatment, and early survivorship of breast
      cancer. A qualitative analysis of discourse posted on breast cancer discussion
      boards and weblogs using the constant comparative method and open-coding
      techniques revealed 12 sources of stress. Using axial coding methods and probing
      these topics for underlying relationship and communication issues yielded 5
      themes. The discussion highlights the implications of the findings for the
      theories that guided this investigation and for breast cancer survivorship more
      generally.

PMID- 19089703
TI  - Meanings of health: interrogating structure and culture.
AB  - Based on the argument that context ought to be centralized in discourses of
      health communication, this article applies the culture-centered approach to
      engage in dialogue about issues of health with 18 men in rural West Bengal. The
      culture-centered approach is based on dialogue between the researcher and the
      community members, with the goals of listening to the voices of cultural members
      in suggesting culture-based health solutions. In this project, our discursive
      engagement with the participants suggests that health is primarily constructed as
      an absence, framed in the realm of minimal access to healthcare resources. In a
      situation where the resources are limited, the participants discussed the
      importance of trust in their relationship with the local provider. Health was
      also seen as a collective resource that was both an asset of the collective and a
      responsibility of the collective. Finally, the participants also pointed out the
      ways in which corruption in the structure introduced a paradox in policy
      discourse and the material conditions of the participants.

PMID- 19089704
TI  - Food advertising during children's television programming on broadcast and cable
      channels.
AB  - The rise in the number of overweight and obese children in the United States is
      recognized as a serious health threat. Among the factors contributing to this
      increase is the preponderance of food marketing on television targeted at
      children. Previous content analysis studies have identified patterns of food
      product types that are commonly associated with unhealthy diets, but few have
      attempted to independently evaluate the nutritional quality of advertised foods.
      This study identifies the nature and extent of food marketing messages presented
      during children's television programs, while also classifying the products
      advertised using a U.S. Department of Health and Human Services consumer food
      rating scheme. The findings indicate that food advertising accounts for nearly
      half of all commercial messages on children's programs. An average hour includes
      11 food ads that account for 4:25 of total ad time. Broadcast channels deliver
      more food advertising than cable channels, although the types of food products
      marketed on both channels are highly similar. The overwhelming majority of foods
      ads directed to children are for high-calorie, low nutrient food products that
      should not be part of a regular diet. These data provide a baseline for
      evaluating anticipated future industry efforts at reform, such as attempts to
      comply with a recent Institute of Medicine (2006) policy recommendation that food
      marketing to children should be balanced between more healthy and less healthy
      food products within two years time.

PMID- 19089707
TI  - Increased obesity in children living in rural communities of Louisiana.
AB  - OBJECTIVE: Rates of obesity among children have been rising in recent years.
      Information on the prevalence of obesity in children living in rural communities
      is needed. We report the prevalence of overweight and obesity in children
      enrolled in grades 4 to 6 who live in rural areas of Louisiana, USA. METHODS AND
      PROCEDURES: These data were collected as baseline assessment for the Louisiana
      (LA) Health project. Height, weight, and estimates of body fat (using body
      impedance analysis) were collected on 2 709 children. Average age was 10.5 years
      and the sample composition was 57.3% girls, 61.7% African-American, 36.0%
      Caucasian, and 2.3% other minority. A majority of children (77%) met the
      criterion for poverty status. RESULTS: The distribution of body mass index (BMI)
      percentile was highly skewed toward obesity. The most frequent BMI percentile
      scores were 98(th) and 99(th) percentile. Using Centers for Disease Control and
      Prevention (CDC) norms, the overall prevalence of obesity was 27.4%, and for
      overweight was 45.1%, of which 17.7% were between the 85(th) and 95(th)
      percentile. The prevalence of childhood overweight and obesity were much higher
      than the national norm and this increased prevalence was observed in both genders
      and in Caucasian and African-American children. DISCUSSION: The prevalence of
      childhood overweight and obesity was found to be much higher in rural and
      primarily poor (77%) children living in Louisiana when compared with national
      norms. This observation suggests that rural children from Louisiana may be
      experiencing an epidemic of obesity that exceeds national prevalence estimates.

PMID- 19089708
TI  - Level and fate of chlorpropham in potatoes during storage and processing.
AB  - Chlorpropham (isopropyl 3-chlorocarbanilate) is a pesticide used to control
      sprouting of potatoes during long-term storage. The objective of the present
      study was to establish the total chlorpropham residue balance (residues in
      unwashed and washed whole tubers, peeled tubers, peels, boiled and pureed tubers,
      and washing and cooking waters) for two potato varieties after uniform
      application as a function of storage time under different typical storage
      conditions (in a basement, storehouse, and refrigerator) in Lithuania.
      Chlorpropham concentration on washed and unwashed tubers decreased from
      approximately 15 mg kg(- 1) after storage for 28 d to approximately 9 mg kg(- 1)
      after storage for 85 d. Peel concentrations decreased from approximately 50 mg
      kg(- 1) at 5 d after treatment to approximately 20 mg kg(- 1) at 85 d after
      treatment. The average concentration in the two varieties of peeled tubers in the
      three storage facilities was 1 mg kg(- 1). Chlorpropham concentrations in the
      wash water decreased from 3.5 to 1.0 mg L(- 1) when the storage time increased
      from 28 to 85 d. The cooking water concentration similarly decreased, from > 0.2
      mg L(- 1) at 28 d after treatment to > 0.1 mg L(- 1) at 85 d after treatment. The
      results of this study show that chlorpropham concentrations in tubers under these
      typical conditions were below the recently revised levels that are acceptable for
      residues in whole potatoes (30 mg kg(- 1)) and peels (40 mg kg(- 1)). Also,
      despite fluctuating conditions during storage, chlorpropham treated tubers did
      not sprout, as compared to untreated tubers, which sprouted.

PMID- 19089709
TI  - Sorption and photodegradation of chlorpyrifos on riparian and aquatic
      macrophytes.
AB  - Surface water bodies may become contaminated via spray drift following pesticide
      application. In this investigation, the photodegradation and sorption of
      chlorpyrifos was studied in four riparian macrophytes representative of
      Mediterranean flora (Phragmites australis, Iris pseudacorus, Equisetum pratense
      and Typha latifolia). The results of experiments with both the active ingredient
      and the formulation DURSBAN 48 EC confirm the ability of these species to
      interact with chemicals such as chlorpyrifos. The maximum sorption of
      chlorpyrifos at equilibrium was observed in Phragmites australis (22%). And, the
      maximum instantaneous sorption of chlorpyrifos was observed in the dried biomass
      of Phragmites australis (49%). The epicuticular waxes present on leaves influence
      photodegradation processes, resulting in a decrease in chlorpyrifos persistence
      depending on the nature of the extract. The half-life of chlorpyrifos residues in
      leaf waxes decreased from 34 to 99 minutes when irradiated.

PMID- 19089710
TI  - Effect of insecticide fenamiphos on soil microbial activities in Australian and
      Ecuadorean soils.
AB  - The effect of fenamiphos, a widely used organophosphorus pesticide, on important
      soil microbial activities such as dehydrogenase, urease and potential
      nitrification in four soils from Australia and Ecuador were studied. The results
      showed fenamiphos in general was not toxic to dehydrogenase and urease up to 100
      mg/Kg soil. However potential nitrification was found to be highly sensitive to
      fenamiphos with a significant inhibition recorded even at 10 mg/Kg soil. In
      general, the nitrification activity in soils was decreased with an increase in
      fenamiphos concentration. The calculated EC(50) values for nitrification in all
      the tested soils ranged between 19 and 56 mg fenamiphos/kg dry soil. This study
      suggests that fenamiphos is likely to be detrimental to nitrification at field
      application rates.

PMID- 19089711
TI  - Biodegradation of mixed pesticides by mixed pesticide enriched cultures.
AB  - This paper discusses the degradation kinetics of mixed (lindane, methyl parathion
      and carbofuran) pesticides by mixed pesticide enriched cultures (MEC) under
      various environmental conditions. The bacterial strains isolated from the mixed
      microbial consortium were identified as Pseudomonas aeruginosa (MTCC 9236),
      Bacillus sp. (MTCC 9235) and Chryseobacterium joostei (MTCC 9237). Batch studies
      were conducted to estimate the biokinetic parameters like the maximum specific
      growth rate (mu(max)), Yield Coefficient (Y(T)), half saturation concentration
      (K(s)) and inhibition concentration (Ki) for individual and mixed pesticide
      enriched cultures. The cultures enriched in a particular pollutant always showed
      high growth rate and low inhibition in that particular pollutant compared to MEC.
      After seven weeks of incubation, mixed pesticide enriched cultures were able to
      degrade 72% lindane, 95% carbofuran and 100% of methyl parathion in facultative
      co-metabolic conditions. In aerobic systems, degradation efficiencies of lindane
      methyl parathion and carbofuran were increased by the addition of 2g L(- 1) of
      dextrose. Though many metabolic compounds of mixed pesticides were observed at
      different time intervals, none of the metabolites were persistent. Based on the
      observed metabolites, a degradation pathway was postulated for different
      pesticides under various environmental conditions.

PMID- 19089712
TI  - Leaching of Diuron, Linuron and their main metabolites in undisturbed field
      lysimeters.
AB  - The increasing use of pesticides in Morocco raises the potential risk of
      groundwater contamination, notably in the Gharb area, which has a shallow
      groundwater table. Thus, the leaching of two phenyl-ureas, diuron and linuron and
      their metabolites through undisturbed soil columns was studied under outdoor
      conditions. The soil chosen is a loamy clay soil, representative of the Gharb
      agricultural area. After four irrigation events were applied from 31/03/2005 to
      15/05/2005, leachates contained higher amounts of linuron (from 0.08% to 6.96% of
      applied linuron) than diuron (from 0% to 0.27%). The greater mobility of linuron
      might be related to its higher water solubility (64 mg x L(- 1) compared with 42
      mg x L(- 1) for diuron) and smaller adsorption coefficient (K(oc) of 400 L x kg(-
      1), compared with 480 L x kg(- 1) for diuron). Concerning their metabolites,
      greater amounts of, N'-(3,4-dichlorophenyl)-N, (DCPMU) than N'-3,4
      dichlorophenylurea (DCPU) were detected N-dimethylurea in the percolates, from 0%
      to 0.046% and from 0% to 0.008%, respectively. At the end of the monitoring
      period, more linuron residues than diuron residues were recovered in the soil
      profiles, 25.02% and 16.41%, respectively. The diuron residues were found mainly
      in the 0-20 cm soil layer, whereas linuron residues reached the 20-40 cm soil
      layer. Under such experimental conditions, linuron leaching, and thus its
      potential to contaminate groundwater, is greater than that of diuron.

PMID- 19089714
TI  - Oxidative stress and structure-activity relationship in the zebrafish (Danio
      rerio) under exposure to paclobutrazol.
AB  - The acute toxicity and changes in the activity of antioxidant enzymes including
      superoxide dismutase (SOD) and catalase (CAT) in the zebrafish Danio rerio were
      measured when the fish was exposed to paclobutrazol (PBZ) under laboratory
      conditions. The median lethal concentration value at 96 h post-exposure (LC(50)
      (96 h)) was determined to be 20.55 mg/L. In addition, the SOD activities in D.
      rerio were significantly higher at 96 h post-exposure among the various
      concentrations of the pollutant tested. The change of CAT activity could be
      considered as a sensitive biomarker of the oxidative stress induced by PBZ. The
      structure-activity relationship (SAR) analysis identified the potential active
      points for the pollutant and that the cavum may be the site of interaction with
      the receptor.

PMID- 19089713
TI  - Acute and chronic toxicity of organophosphate monocrotophos to Daphnia magna.
AB  - The acute and chronic toxicity of monocrotophos (MCP), the binary joint toxicity
      of MCP and bifenthrin (BF), and sodium dodecyl benzene sulfonate (SDBS) to
      Daphnia magna (D. magna) was evaluated. The 24 h-median effective concentration
      (24 h-EC(50)) and 48 h-median lethal concentration (48 h-LC(50)) of MCP towards
      D. magna were 161 and 388 micro g/L, respectively. In addition, the lowest
      observed effective concentration (LOEC) and non-observed effective concentration
      (NOEC) of MCP to D. magna were 10 and 5 micro g/L, respectively. Furthermore, the
      chronic value (ChV) of MCP against D. magna was 7 micro g/L and the acute chronic
      ratio (ACR) was 55. The number of offspring per female and the intrinsic rate of
      natural increase (r) were identified as the parameters that were most sensitive
      to MCP. In addition, toxic unit (TU) analysis was employed to evaluate the joint
      toxicities. The calculated TU(mix) values of binary equitoxic mixtures of MCP +
      BF and MCP + SDBS were 1.47 and 1.63, respectively, which suggests that both
      equitoxic mixtures exert a limited antagonistic effect. The results of this study
      revealed that the toxic threshold of MCP towards D. magna is higher than its
      reported highest residue (4 micro g/L) in the ordinary aquatic environment, and
      that concurrent exposure to BF or SDBS may exert a slight antagonistic effect.

PMID- 19089715
TI  - Evaluation of the fate of the active ingredients of insecticide sprays used
      indoors.
AB  - The fate of the active ingredients of insecticide sprays after use in indoor
      environments was investigated. Indoor air sampling was performed through two
      types of adsorbents, namely, TENAX TA and XAD-2 (10 L). After sampling, both
      adsorbents were ultrasonically extracted and analyzed by Gas Chromatography
      coupled to Mass Spectroscopy. The separation and analysis of the selected
      compounds were satisfactory and fast (duration of the chromatographic run: 40
      min). The method was linear for all examined chemicals over the tested range (2
      to 50 ng of absolute compound); limits of detection ranged from 0.42 to 1.32 ng
      of absolute compound. The method was then applied in the determination of the
      active ingredients of three commercially available insecticide sprays that were
      separately used in a full-scale environmental chamber (30 m(3)). After spraying,
      the fate of the active ingredients [propoxur, piperonyl butoxide (PBO) and
      pyrethrin insecticides] was monitored over 40 minutes, with and without
      ventilation. Both adsorbent materials were proven to be efficient and the
      differences in the concentrations deriving from sampling with both materials were
      in almost all cases less than 10%. All chemicals were removed in rates that
      exceeded 80%, after the 40 minutes of monitoring, exhibiting different decay
      rates. The removal of insecticides was not significantly affected by the
      ventilation of the chamber. The correlation analysis of propoxur, PBO and
      pyrethrins with the aerosols of various sizes (15 fractions, from 0.3 to > 20
      microm) showed that propoxur and PBO mainly associated with the medium size
      aerosols (3-7.5 microm) while pyrethrins seem to link more with heavier particles
      (> 10 microm).

PMID- 19089716
TI  - Multiresidue method for high-performance liquid chromatography determination of
      carbamate pesticides residues in tea samples.
AB  - A multiresidue method was developed to determine 19 carbamate pesticides in tea
      samples. Optimizations of different parameters, such as the type of extraction
      solvents, clean-up cartridges, and elution solvents were carried out. The
      developed method used acetonitrile as extraction solvent, amino cartridge for
      adsorbents and acetone-n-hexane as the eluting solution. Nineteen carbamate
      residues were then analyzed by high-pressure liquid chromatography (HPLC) with
      fluorescence detector. The present results showed good linearity by correlation
      coefficients of more than 0.9999 for all analyses. Limits of detection and
      quantification varied from 0.0005-0.023 mg L(- 1), 0.008-0.077 mg L(- 1),
      respectively. Recoveries of sixteen carbamate pesticides ranged from 65% to 135%
      at the spiked level of 0.5, 1.0 and 2.0 mg L(- 1). The relative standard
      deviations were lower than 20% and coefficient of variations were lower than 15%.
      The results indicate that the proposed method provides an effective multi and
      trace level screening determination of carbamate pesticides residues for tea
      samples.

PMID- 19089717
TI  - Comparative study of accessibility of distinctive pesticides.
AB  - Interactions of micro-contaminants with soil may play a crucial role in their
      environmental fate and possible harmful effects. Major goals of our
      investigations were to model the availability of widely used pesticides and
      characterize adsorption capabilities of distinctive soil types by the
      accomplishment of extensive comparative studies and application of several
      extraction methods. Environmental and biological relevance of these examinations
      is enhanced by the fact that intrinsic features and specific details of pesticide
      accessibility have not been revealed so far by a comparative approach. Five
      different experimental methods were assessed for modelling accessibility of five
      selected pesticides. The applied models for regaining the pesticides showed
      diverse efficiency in extraction capability in cases of the different soil types
      (sandy, brown forest and alluvial soils). The amounts of the obtained pesticides
      were determined by using gas-chromatography coupled to mass spectrometry (GC-MS)
      and high pressure liquid chromatography coupled to mass spectrometry (HPLC-MS).
      Accessibility of pesticides was also compared in cases of sterilized and real
      soil samples in order to estimate the extent of the influence of microflora.
      Aqueous extraction solvents proved to be suitable for accurate assessment of the
      accessible amounts of pesticides, as their effectivity was at least as high as
      that of the applied organic solvents. In our studies pesticide-soil interactions
      have comprehensively been characterized, and possible influences of environmental
      factors on the accessibility have also been revealed. Our study might be regarded
      as a tentative approach to model some significant circumstances playing key roles
      in pesticides' possible bioavailability.

PMID- 19089719
TI  - Combined effects of exposure time and copper toxicity on the demography of Moina
      macrocopa (Crustacea: Cladocera).
AB  - Cohort life table experiments were conducted on M. macrocopa using copper at
      three nominal concentrations (as CuSO(4), 0.1, 0.2 and 0.4 mg L(- 1), in addition
      to controls) for different periods of exposure (3 to 24 h). Age-specific
      survivorship of M. macrocopa decreased in relation to age of the cohort,
      concentration and duration of exposure to copper. Age-specific life expectancy
      curves also decreased with increasing age of the cohort. However, at low copper
      levels and shorter exposure time, there was an increase in life expectancy when
      the cohort was about 10 day old. Fecundity (m(x)) was nearly regular in controls;
      however, at higher copper levels and longer duration of exposure, the offspring
      production was more oscillating. The offspring production completely ceased when
      continuously exposed to CuSO(4) at 0.4 mg L(- 1). Most of the measured demography
      variables significantly decreased with increasing concentration of Cu in the
      medium. The average lifespan and life expectancy at birth varied 2.9 to 9.6 and
      2.4 to 9.1 days, respectively. Gross reproductive rate (GRR) varied from 31 to 89
      offspring female(- 1) lifespan(- 1), while the survival-weighted net reproductive
      rates were nearly one-third of the GRR. Generation time of M. macrocopa varied
      from 5 to 7 days while the rate of population increase ranged from 0.36 to 0.84
      per day. The results are discussed in relation to the sensitivity of M. macrocopa
      to copper toxicity and the necessity of amending the national water quality
      criteria in Mexico.

PMID- 19089718
TI  - Manure placement depth impacts on crop yields and N retained in soil.
AB  - The objective of this study was to determine the impact of manure placement depth
      on crop yield and N retention in soil. Experimental treatments were deep manure
      injection (45 cm), shallow manure injection (15 cm), and conventional fertilizer
      based management with at least three replications per site. Water infiltration,
      and changes in soil N and P amounts were measured for up to 30 months and crop
      yield monitored for three seasons following initial treatment. Deep and shallow
      manure injections differed in soil inorganic N distributions. For example, in the
      manure slot the spring following application, NO(3)-N in the surface 60 cm was
      higher (p < .01) when injected 15 cm (21.4 micro g/g) into the soil than 45 cm
      (11.7 micro g/g), whereas NH(4)-N had opposite results with shallow injection
      having less (p = 0.045) NH(4)-N (102 micro g/g) than deep (133 micro g/g)
      injection. In the fall one year after the manure was applied, NO(3)-N and NH(4)-N
      were lower (p = 0.001) in the shallow injection than the deep injection. The net
      impact of manure placement on total N was that deep injection had 31, 59, and 44
      more kg N ha(- 1) than the shallow injection treatment 12, 18, and 30 months
      after application, respectively. Deep manure injection did not impact soybean
      (Glycine max L.) yield, however corn (Zea mays L.) yield increased if N was
      limiting. The higher corn yield in the deep injected treatment was attributed to
      increased N use efficiency. Higher inorganic N amounts in the deep injection
      treatment were attributed to reduced N losses through ammonia volatilization,
      leaching, or denitrification. Results suggest that deep manure placement in
      glacial till soil may be considered a technique to increase energy, N use
      efficiency, and maintain surface and ground water quality. However, this
      technique may not work in glacial outwash soils due to the inability to inject
      into a rocky subsurface.

PMID- 19089721
TI  - Evaluating the effectiveness of curriculum change. Is there a difference between
      graduating student outcomes from two different curricula?
AB  - BACKGROUND: Changing a curriculum raises the question whether the results, new
      curriculum student outcomes, are different from old curriculum student outcomes.
      AIMS: To see whether different curricula produce different outcomes, we compared
      test and questionnaire results of two cohorts. We wanted to know if there is a
      difference on knowledge and skills test results, and on the number of times
      students practiced their skills during their final internships. METHOD: We used
      two validated test instruments: the Dutch Progress Test (PT) and the Objective
      Structured Clinical Examination (OSCE). For reporting their skills practice, we
      asked students of both cohorts to fill out a basic skills questionnaire. RESULTS:
      We found no significant difference between both cohorts on the results of their
      knowledge test and their report on skills practice. On the OSCE, students from
      the new curriculum cohort scored significantly higher than old curriculum
      students. CONCLUSION: Curriculum change can lead to improvements in graduating
      students' outcome results.

PMID- 19089722
TI  - Creating a culture of thoughtful prescribing.
AB  - BACKGROUND: In the Netherlands 170,000 patients yearly fall victim to poor
      communication between health care professionals,with 44% of patients receiving
      inappropriate therapy as a result. Evidence indicates that this problem may be
      due to physicians learning to communicate therapeutic content by unstructured
      means during training. AIM: To introduce a structured format for creating and
      communicating therapeutic plans; to provide for students opportunities to
      practice and feedback on their abilities. METHODS: We developed the
      Individualized Therapy Evaluation and Plan (ITEP) for therapeutic decision-making
      and communication based on the subjective objective assessment and plan note. The
      therapeutic plans from students of the 2003 cohort were assessed with one simple
      and one complex case using a 15-point criteria form. Over the next 3 years
      students were given more practice using the ITEP and the average score on the
      complex case was tracked and compared to the 2003 cohort. RESULTS: In cohort
      2003, 82% of the students satisfactorily completed the simple case, while only
      32% did so with the complex case. In subsequent years, the average scores on the
      complex case significantly improved from 3.8 to 6.8 with increasing practice.
      CONCLUSIONS: Students can select a simple drug regimen, but without practice
      using the ITEP will not help to deal with multiple disease states.

PMID- 19089723
TI  - Assessing postgraduate trainees in Canada: are we achieving diversity in methods?
AB  - BACKGROUND: Resident evaluation is a complex and challenging task, and little is
      known about what assessment methods, predominate within or across specialties.
      AIMS: To determine the methods program directors in Canada use to assess
      residents and their perceptions of how evaluation could be improved. METHODS: We
      conducted a web-based survey of program directors from The Royal College of
      Physicians and Surgeons of Canada (RCPSC)-accredited training programs, to
      examine the use of the In-Training Evaluation Report (ITER), the use of non-ITER
      tools and program directors' perceived needs for improvement in evaluation
      methods. RESULTS: One hundred forty-nine of the eligible 280 program directors
      participated in the survey. ITERs were used by all but one program. Of the non
      ITER tools, multiple choice questions (71.8%) and oral examinations (85.9%) were
      most utilized, whereas essays (11.4%) and simulations (28.2%) were least used
      across all specialties. Surgical specialties had significantly higher multiple
      choice questions and logbook utilization, whereas medical specialties were
      significantly more likely to include Objective Stuctured Clinical Examinations
      (OSCEs). Program directors expressed a strong need for national collaboration
      between programs within a specialty to improve the resident evaluation processes.
      CONCLUSIONS: Program directors use a variety of methods to assess trainees. They
      continue to rely heavily on the ITER, but are using other tools.

PMID- 19089724
TI  - Physiotherapy students' and clinical teachers' perceptions of clinical learning
      opportunities: a case study.
AB  - BACKGROUND: The attainment of clinical competence is a key outcome of
      physiotherapy programmes worldwide. Clinical education forms a core component of
      the training of physiotherapy students. AIMS: The study on which this article is
      based aimed to investigate what physiotherapy students and clinical teachers at
      one physiotherapy training institution perceive as effective opportunities to
      facilitate learning in a clinical context. METHODS: A survey of staff and
      students at the physiotherapy division at Stellenbosch University was undertaken
      as one element of a situational case study. All enrolled physiotherapy students
      with clinical education experience and all clinical teachers involved in the
      clinical education of these students were invited to participate. A purpose-built
      questionnaire was developed and validated before being administered. RESULTS: The
      response rate was 80%. The clinical teaching and learning opportunities deemed
      most valuable for learning by students and teachers were demonstrations of
      patient management, feedback, discussions and assessment. Teachers and students
      varied in their perceptions of the learning value of peer assessment, self
      assessment and reflection. CONCLUSIONS: The study provided indications for
      teachers on the valuable learning opportunities as perceived by students and
      teachers in a physiotherapy clinical setting. The activities perceived as most
      effective in facilitating learning in the clinical milieu were demonstrations of
      patient management, discussion, feedback and assessment. Participants indicated
      that they valued individual contact with teachers and that they learnt
      productively from discussions with the teachers. It was reported that immediate
      and verbal feedback improved the learning experience. Both formative assessment
      in the form of a mock assessment and summative assessment in the form of an end
      of-block test were identified as important in facilitating learning. Further
      research is required on peer assessment, self-assessment and reflection to
      establish the role of these aspects of learning.

PMID- 19089726
TI  - Educating capable doctors--a portfolio approach. Linking learning and assessment.
AB  - BACKGROUND: Teachers want students to focus on their learning to become capable
      doctors; yet, students primarily want to focus on passing their exams. How much
      of this paradox is explained by learning and assessment being seen as two
      different entities rather than as the continuum of one and the same process? How
      may the two areas be more closely and effectively linked? AIM: This article
      describes and illustrates a conceptual framework for an approach termed
      capability-based portfolio assessment. RESULTS AND CONCLUSIONS: Thinking about
      capability, i.e. the ability to perform in the real world, is needed for a
      contemporary curriculum and assessment design. A capability-focus will help
      students to integrate the foundations of medical practice with learning how to
      become a capable, reflective and life-long learner. A well-structured capability
      portfolio, regularly presented and reviewed, will be a useful tool to guide the
      journey, and should have the potential to help drive deep learning and allow the
      assessment of capabilities that are hard to assess using conventional approaches.
      Assessment based on portfolio approaches should not equate to increasing the
      overall assessment burden as it will reduce the need for more traditional
      assessment methods.

PMID- 19089725
TI  - Comparison of the self-reported training level between Mexican and Western Europe
      residents in urology: results of an international survey.
AB  - OBJECTIVE: To find out how Mexican residents in urology perceive their own level
      of training in comparison with how residents in Europe perceive theirs. METHODS:
      A questionnaire of self-assessment was distributed to 104 European and 24 Mexican
      urologists-in-training. We assessed the perception of residents about their level
      of training and factors associated with self-perceived performance. RESULTS: Mean
      age of 128 residents was 32.69 +/- 3.33 years. Mexican residents spent
      significantly more time in urological departments than European residents. The
      weekly amount of hours spent at work was higher in Europe; while the number of
      residents per hospital was higher in Mexico. Mexican residents reported more
      reliable support from a supervising senior. European residents perceived they had
      a superior level regarding transplantation in female urology and urinary
      lithiasis, whereas Mexican residents felt more confident regarding urological
      infections and paediatric urology. Factors associated with better self-perceived
      performance were the number of months in urology, the number of non-urologic
      rotations and a supervising senior. CONCLUSION: Mexican residents in urology
      perceive that their own level of training is similar to that of European
      residents. The number of months of training in urology, the number of non
      urologic rotations and a supporting senior are associated with a better self
      perceived performance.

PMID- 19089727
TI  - The role of living models in the teaching of surface anatomy: some experiences
      from a UK Medical School.
AB  - BACKGROUND: Despite recommendations stemming from the 1930s espousing the value
      of a living anatomy component in undergraduate medical education, living anatomy
      remains relatively under described. AIM: In this article, we explore the role of
      the living anatomy model in living anatomy teaching. METHOD: Our report is based
      on a larger ethnographic study of living anatomy classes, undertaken at Peninsula
      Medical School between 2002 and 2004. A Research Fellow participated as an
      observer in 24 Year One and Year Two anatomy classes in which living anatomy
      models were employed. The findings are based on field notes and conversations
      with models, students and tutors. RESULTS AND CONCLUSIONS: Within the supervised
      context of the anatomy class the living models assisted students in the learning
      of structure, function, surface anatomy and body variation. Far from being
      'passive sites' for the students to practice their anatomical knowledge, the
      living models were active participants in class, assisting students with their
      communication skills, sharing anatomical knowledge, offering guidance to staff
      and sharing their past medical history and experiences. Living anatomy models can
      foster an additional dimension of humanitarian thinking within the anatomy class;
      however, further research needs to focus on the power messages implicit in the
      organization of sessions.

PMID- 19089728
TI  - Necessary steps in factor analysis: enhancing validation studies of educational
      instruments. The PHEEM applied to clerks as an example.
AB  - BACKGROUND: The validation of educational instruments, in particular the
      employment of factor analysis, can be improved in many instances. AIMS: To
      demonstrate the superiority of a sophisticated method of factor analysis,
      implying an integration of recommendations described in the factor analysis
      literature, over often employed limited applications of factor analysis. We
      demonstrate the essential steps, focusing on the Postgraduate Hospital
      Educational Environment Measure (PHEEM). METHOD: The PHEEM was completed by 279
      clerks. We performed Principal Component Analysis (PCA) with varimax rotation. A
      combination of three psychometric criteria was applied: scree plot, eigenvalues
      >1.5 and a minimum percentage of additionally explained variance of approximately
      5%. Furthermore, four interpretability criteria were used. Confirmatory factor
      analysis was performed to verify the original scale structure. RESULTS: Our
      method yielded three interpretable and practically useful dimensions: learning
      content and coaching, beneficial affective climate and external regulation.
      Additionally, combining several criteria reduced the risk of overfactoring and
      underfactoring. Furthermore, the resulting dimensions corresponded with three
      learning functions essential to high-quality learning, thus strengthening our
      findings. Confirmatory factor analysis disproved the original scale structure.
      CONCLUSIONS: Our sophisticated approach yielded several advantages over methods
      applied in previous validation studies. Therefore, we recommend this method in
      validation studies to achieve best practice.

PMID- 19089729
TI  - Exploring temperament and character traits in medical students; a new approach to
      increase the rural workforce.
AB  - BACKGROUND: This study explored temperament and character traits in medical
      students to identify the possible predictive value of these traits to students
      with varying levels of intention to pursue rural medicine. This work is the
      precursor to a better understanding of personality traits associated with medical
      disciplines within specific environments such as rural medicine. AIMS: The long
      term aim is to increase the recruitment of students who are best suited, and
      choose to practice in rural locations. METHODS: Medical students (272) completed
      a demographic survey and the Temperament and Character Inventory (TCI-R 140) to
      identify levels of the seven basic dimensions of temperament and character.
      Multivariate statistics explored differences between students' TCI levels based
      on gender, rural origin and level of intention to pursue rural medicine. RESULTS:
      Analysis showed only main effects and confirmed significant differences in
      certain TCI dimensions between students with a high compared to a low or medium
      intention to practice rural medicine and between males and females. CONCLUSIONS:
      Preliminary findings suggest that certain temperament and character traits may be
      related to interest in rural medicine however the efficacy of assessing
      personality traits as an adjunct to medical school training and career
      counselling remains uncertain.

PMID- 19089730
TI  - A programme of accelerated medical education in Taiwan.
AB  - BACKGROUND: Graduates of the 7-year undergraduate medical curriculum in Taiwan
      are often deficient in clinical skills. AIMS: To implement and assess a programme
      of accelerated clinical education. METHOD: The Department of Primary Care
      Medicine at the National Taiwan University College of Medicine implemented a
      programme shortening the undergraduate clinical curriculum from 3 to 2 years and
      giving students more clinical responsibility. Students were prepared for clinical
      rotations with a 1-month clinical skills course. Core clinical rotations were
      redesigned to be more participatory. The programme included 1 year of a
      postgraduate, rotating residency. Self-selected students with adequate grades,
      recommendations and performance on an interview participated in the programme.
      None of them dropped out. RESULTS: Compared with their traditionally instructed
      cohorts, graduates of the accelerated programme ( approximately 10% of each
      class) were more likely to pass national boards (100% versus 80-97%) and were
      rated as more proficient on 9 of the 10 different clinical performance parameters
      (p < 0.01 by sign test). Sixty-nine percent reported being satisfied or very
      satisfied with the programme. CONCLUSION: A pilot programme of accelerated
      medical education at National Taiwan University that included clinical skills
      instruction, mentor-style classes and active learning techniques resulted in
      satisfactory outcomes for the students selected for the programme.

PMID- 19089731
TI  - Faculty physicians and new physicians disagree about which procedures are
      essential to learn in medical school.
AB  - BACKGROUND: Clinical procedures taught in the undergraduate medical curriculum
      are important for subsequent residency training and clinical practice. Published
      reports suggest that medical schools may not be adequately teaching procedures.
      This study identifies procedures considered essential by residents completing
      internship and by medical school faculty, and determines agreement on their
      importance for medical student education. METHODS: Two hundred and thirty-five
      physicians (184 new physicians who recently completed internship and 51 medical
      school teaching faculty) categorized 31 clinical procedures based on the
      importance for internship. New physicians who had completed internship reported
      the level of training received in medical school for each procedure. RESULTS:
      Survey responses were 76% (faculty) and 70% (new physicians who had completed
      internship). The faculty majority identified 14 procedures as 'Must Know.' New
      physicians disagreed on 8 of these and categorized an additional 5 as essential.
      There was 32% concordance for the 19 procedures identified by either group. New
      physicians reported 'Limited Hands-On Training' for all 19 procedures but
      'Comprehensive Hands-On Training' for only two. CONCLUSIONS: New physicians who
      have completed internship and medical school faculty do not agree on procedures
      essential for internship. A core educational list of 19 procedures was identified
      using the responses from these two groups.

PMID- 19089732
TI  - All health care providers must learn how to work efficiently with interpreters
      and respect patients' values and preferences.

PMID- 19089733
TI  - Evaluating training for a simulated team in complex whole procedure simulations
      in the endovascular suite.
AB  - INTRODUCTION: Simulators supporting the development of technical skills for
      complex procedures are gaining prominence. Safe performance of complex procedures
      requires effective team interactions. Our research group creates 'whole'
      procedure simulations to produce the psychological fidelity of clinical settings.
      Recruitment of real interventional team (IT) members has proved challenging.
      Actors as a simulated team are expensive. We hypothesised that medical students
      and trainees in a vascular unit could authentically portray members of the
      endovascular suite for carotid stenting. METHODS: This paper describes the
      evaluation of a training programme for a simulated IT. Participants rated the
      extent to which programmes objectives were met and realism of simulations.
      Researchers' field notes provided insight into strengths and weaknesses of the
      programme. RESULTS: Seven members from the vascular unit undertook training.
      Learning objectives were largely met. Nineteen simulations with 13
      interventionalists were performed. Realism levels were at least moderate.
      Simulated IT members reported increased understanding of teamwork and roles in
      the endovascular suite. DISCUSSION: A simulated IT proved feasible. Authentic
      psychological fidelity complemented the physical fidelity of the simulated suite.
      Although there were areas for development in training, this approach might
      contribute considerably to interventionalist training and increase knowledge and
      skills of vascular trainees and medical students.

PMID- 19089734
TI  - Special theme issue: breast pathology.

PMID- 19089735
TI  - Pre-operative diagnosis of breast cancer in screening: problems and pitfalls.
AB  - The widespread use of mammographic breast screening and the introduction of even
      more sensitive radiological techniques have placed increasing demands upon the
      pathologist for the accurate diagnosis and histological categorisation of screen
      detected lesions. Subsequent management algorithms rely on correct pathological
      classification. Needle core biopsy (NCB) has become the mainstay of non-operative
      diagnosis in many Breast Units. However, despite good specificity and
      sensitivity, there remain lesions that are particularly challenging on NCB. This
      may be because they can mimic invasive carcinoma or because there is a risk of
      associated carcinoma. Particular areas of difficulty arise as a result of the
      focal nature of sampling inherent with biopsy specimens. Troublesome lesions
      include atypical epithelial proliferations, sclerosing lesions and radial scars,
      papillary, columnar cell and apocrine lesions and lobular in situ neoplasia.
      Immunohistochemistry can be helpful in clarifying the nature of some of these
      lesions in NCB material but subsequent management nevertheless often remains
      controversial. Finally, special type invasive carcinomas such as lobular and
      metaplastic cancers and non-primary malignancies such as lymphoma and metastasis
      can be misdiagnosed in the limited material of a NCB, particularly if not
      considered in the differential diagnosis. Good communication between clinician,
      radiologist and pathologist is especially important in the breast screening
      setting, in order to avoid misdiagnosis, ensure correct categorisation of NCB
      samples and to ensure optimum patient care.

PMID- 19089736
TI  - Columnar cell lesions of the breast: an update and significance on core biopsy.
AB  - Columnar cell lesions of the breast refer to the morphological spectrum of
      alterations of the epithelial lining of variably dilated acini of the terminal
      duct lobular unit (TDLU), often related to secretions and calcifications. After
      decades of varied terminologies, the term of 'flat epithelial atypia' by the
      World Health Organization (WHO) consensus group encompasses the part of the
      spectrum where columnar cell change or columnar cell hyperplasia acquires low
      grade cytological atypia, merging with atypical ductal hyperplasia and low grade
      ductal carcinoma in situ. Its association with low grade invasive carcinoma and
      lobular neoplasia, whether by proximity to these lesions, or by similar molecular
      expressions, has prompted greater scrutiny into its clinical significance.
      Although recent literature attempts to refine the term 'flat epithelial atypia',
      the applicability of its morphological criteria in routine diagnostic practice
      remains to be seen, and interobserver variability is highly possible. This poses
      even greater challenges especially in limited samples of breast tissue, such as
      in core biopsies, for pre-operative decision-making. The purpose of this review
      is to elucidate evolving clinical and diagnostically relevant principles that
      surround and influence the significance of this still controversial entity,
      especially when discovered on core biopsy in the initial phase of breast
      diagnosis and management.

PMID- 19089737
TI  - Lobular neoplasia of the breast: 68 years on.
AB  - Lobular neoplasia, which encompasses both atypical lobular hyperplasia and
      lobular carcinoma in situ, is traditionally considered a risk lesion that
      indicates an increased relative risk of the affected woman for subsequent breast
      cancer development. Recent molecular genetic information on this entity, however,
      has provided additional insights into the biology of this incompletely understood
      disease. Recognition of variants of lobular carcinoma in situ has also led to
      dilemmas in optimal management, and the advent of pre-operative core biopsies for
      radiologically detected lesions has created uncertainties regarding how best to
      handle incidentally discovered lobular neoplasia on these biopsy cores. This
      article provides an overview of existing concepts, diagnostic pitfalls,
      pathobiology and current management approaches for this enigmatic lesion.

PMID- 19089738
TI  - Update on atypical epithelial hyperplasia and ductal carcinoma in situ.
AB  - Atypical ductal hyperplasia (ADH) as an indicator of increased risk for
      developing breast cancer is well established. Refinement in its molecular
      characterisation, especially as it relates to risk, continues to be challenging,
      largely because of its small and very focal nature. Also a challenge is
      appropriate management of ADH when present on core biopsy. Additional support for
      ductal carcinoma in situ (DCIS) as a precursor to invasive cancer, as well as
      recent molecular characterisation of DCIS are presented. The importance of margin
      assessment in cases of DCIS and the limited role for sentinel lymph node biopsy
      in this setting are reviewed.

PMID- 19089739
TI  - Triple-negative/basal-like breast cancer: review.
AB  - Breast cancer comprises a heterogeneous group of diseases that vary in
      morphology, biology, behaviour and response to therapy. Triple-negative (TN)
      breast cancer is a subtype of tumours with aggressive clinical behaviour which
      currently lacks effective targeted therapies. The majority of TN breast cancers
      possess a basal phenotype and show varying degrees of basal marker expression
      (basal-like tumours). The importance of recognising these tumours came to light
      largely as the result of global gene expression profiling studies that
      categorised breast cancer into distinct molecular classes. These studies showed
      that basal-like tumours are molecularly different from hormone receptors and HER2
      positive tumours. Although both TN and basal-like tumours share many molecular
      and morphological features, equating both tumour classes may be misleading. A
      better understanding of the molecular and histopathological features of TN and
      basal-like cancers is of paramount importance, in particular for unravelling the
      heterogeneous nature of these tumour subgroups and for the identification of
      prognostic biomarkers, ideal systemic therapy regimens and novel therapeutic
      targets for these aggressive tumours. In this review, we discuss the difference
      between TN and basal-like tumours, pathological and clinical features of basal
      like cancer and hence explore the criteria that can be used to identify these
      tumours in routine practice.

PMID- 19089740
TI  - Rare (new) entities of the breast and medullary carcinoma.
AB  - Rare tumours are a heterogeneous group of conditions that encompass benign to
      malignant lesions both of stromal and epithelial origin. Here some of these
      tumours are described, in which the authors have most familiarity. An outline of
      medullary carcinoma is also presented.

PMID- 19089741
TI  - Synchronous multiple ipsilateral breast cancers: implications for patient
      management.
AB  - Interest in the presence and management of synchronous multiple ipsilateral
      breast cancer has been reported since the early 1920s. The demonstration of
      multiple foci of breast cancer has been reported in 9-75% of breast cancer
      related specimens. The large difference in reported incidence is multifactorial
      and related to the definitions applied, mode of detection and pathological
      assessment. However, randomised clinical trials comparing total mastectomy and
      segmental mastectomy with or without radiation over many years have shown no
      difference in distant disease-free survival or overall survival in patients with
      synchronous multiple ipsilateral breast cancer compared with unifocal breast
      cancer. This review examines the current definitions, incidence, pathological
      assessment, staging and surgical options of synchronous multiple ipsilateral
      breast cancer.

PMID- 19089742
TI  - The role of immunohistochemistry in the differential diagnosis of breast lesions.
AB  - Immunohistochemistry may be helpful in the diagnosis of various breast lesions.
      It can be used to assist in distinguishing benign and malignant conditions, or to
      clarify the histological subtype of invasive carcinomas. There are several
      markers relatively frequently utilised. Myoepithelial markers (p63, alpha-SMA,
      smooth muscle myosin heavy chain, and others) are useful to highlight
      myoepithelial cells. They are employed to verify myoepithelial cell lining in
      intraductal papillary lesions, or to recognise peripheral myoepithelial cells for
      non-invasive carcinoma, although their staining results are not always excellent.
      High molecular weight cytokeratins (CK5/6, CK14, 34betaE12) typically show a
      mosaic-like pattern of expression in benign papillary/hyperplastic lesions, and
      are mostly negative in ductal in situ carcinoma, but some exceptions exist.
      Neuroendocrine differentiation (confirmed by anti-chromogranin A or
      synaptophysin) suggests malignancy in solid and papillary intraductal epithelial
      proliferations. The significance of immunohistochemical evaluation of apocrine
      lesions is still controversial. Negative E-cadherin staining is used for making
      confirmative diagnosis of lobular carcinoma, with a specificity and sensitivity
      of approximately 90%. Cytokeratins, especially the antibody 34betaE12, are of
      value to differentiate spindle cell carcinoma from phyllodes tumour. There are
      some other useful markers for characterising certain histological subtypes.
      Nevertheless, for accurate diagnosis, it is essential to correlate the
      immmunohistochemical staining results with the histological findings.

PMID- 19089743
TI  - The role of molecular analysis in breast cancer.
AB  - Breast cancer is a heterogeneous disease, encompassing a wide variety of
      histological types and clinical behaviours. Current histopathological
      classification systems for breast cancer are based on descriptive entities that
      are of prognostic significance. Few predictive biomarkers are currently
      available. High throughput molecular technologies are reshaping our understanding
      of breast cancer and a molecular taxonomy that has stronger predictive power is
      slowly emerging. Novel therapeutic targets and prognostic/predictive gene
      signatures have been identified. This review will address the contribution of
      molecular methods to our understanding of breast cancer and its precursors, their
      use in breast cancer translational research and their impact on diagnostic breast
      cancer histopathology.

PMID- 19089744
TI  - Current and future approach to the pathologist's assessment for targeted therapy
      in breast cancer.
AB  - Breast cancer is a common disease in the population. Contrary to public
      perception, it is a heterogeneous disease with varying morphology, prognosis and
      response to therapy. The pathological analysis is at the heart of information
      provided to surgeons and oncologists to plan further management. The pathologist
      is increasingly asked to test for biomarkers that provide prognostic and
      predictive information to direct treatment. Staining cancers for ER, PgR and HER2
      has become routine and it is likely that addition of other biomarkers including
      'basal markers', VEGF and growth factor receptors such as HER1 (EGFR) will soon
      follow. Microarray based genomic, transcription and proteomic methods are
      changing our classification systems and identifying novel targets for the
      development of new therapeutics. It is important for pathologists to appreciate
      and embrace the new developments as they will impact on daily clinical practice
      and require accurate assessment of biomarkers to determine treatment options as
      part of multidisciplinary teams.

PMID- 19089745
TI  - Homocyst(e)ine, folate, and vitamin B12 status in a cohort of Welsh young people
      aged 12-13 years old.
AB  - The aim of this unique study was to consider the relationship between folate and
      vitamin B(12) on homocyst(e)ine (Hcy) concentration in an apparently healthy
      cohort of Welsh young people. A cohort of 179, 12-13 year olds (88 boys and 91
      girls) were measured for Hcy, folate, vitamin B(12), adiposity, and dietary
      habits. Boys had significantly higher waist circumference and folate
      concentration than girls. Folate was negatively associated with Hcy in both
      sexes, whereas vitamin B(12) was negatively associated with Hcy in boys only.
      Adiposity was not associated with Hcy. Folate was an independent predictor of Hcy
      in both sexes, whilst vitamin B(12) was an independent determinant of Hcy in boys
      only. Familial history of cardiovascular disease (CVD) risk factors was
      identified in 69% of the children with elevated Hcy (> or = 8.5 mumol.L(-1)).
      Young people might be encouraged to increase their folate intake through diet,
      particularly by increasing their consumption of leafy vegetables and fruit.
      Further research is necessary to determine the exact contribution of genetics and
      diet on Hcy levels in young people, and whether Hcy levels during childhood and
      adolescence might influence future CVD risk.

PMID- 19089746
TI  - Neuromuscular recovery of the biceps brachii muscle after resistance exercise.
AB  - The aim of this study was to determine the time to restore the biceps brachii
      (BB) electromyographic (EMG) activity after the biceps curl (BC) exercise, at
      different intensities. Ten males performed initially maximal voluntary isometric
      contractions (MVC) of the elbow flexors, followed by one isometric submaximal
      contraction at 50% MVC (reference contraction). After this, four bouts of the BC
      at 25%, 30%, 35%, and 40% 1 RM during 1 minute (randomly assigned, with 10
      minutes rest between them) were performed. During the rest intervals at
      preestablished moments (15 seconds, 1, 3, 5, and 10 min), isometric 50% MVC were
      performed. The EMG variables (root mean square [RMS], zero crossings [ZC], median
      frequency, [MF] and peak power [PP]) at rest were compared with reference values.
      Immediately after the exercise, RMS and PP increased, while ZC and MF decreased,
      indicating fatigue. After 1 minute most of the variables were similar to the
      reference. Different load levels did not affect the EMG recovery. In conclusion,
      the EMG variables recovered after 1 minute rest, indicating the optimal muscular
      condition for subsequent bouts.

PMID- 19089747
TI  - Use of antipronation taping to determine foot orthoses prescription: a case
      series.
AB  - In order to determine if the use of antipronation taping could be used to direct
      foot orthoses prescription, seven high school athletes with lower extremity or
      foot pain caused by overuse stress were taped for 3 days during practice
      sessions. A visual pain scale and the Foot and Ankle Ability Measure sports
      subscale were used to monitor pain and function improvement caused by taping. If
      the taping was effective, foot orthotics were fabricated and posted according to
      the change in foot posture created by the tape. After wearing the foot orthotics
      for 4 weeks, all athletes reported a substantial short-term (4-week) reduction in
      pain and an increase in function. The results of this case series indicate that
      changes in foot posture created by taping can be used to guide foot orthosis
      prescription.

PMID- 19089748
TI  - Blood parameters in adults with intellectual disability at rest and after
      endurance exercise.
AB  - Clinically, adult with intellectual disability (ID) appear less physically fit
      than people without ID, yet formal endurance evaluation has not been reported
      previously. We hypothesized that the immune system in adults people with ID can
      be influenced positively from 4 weeks of endurance training. Healthy subjects
      with ID ages from 43 to 55 years were included in the study. The subjects (n =
      22) exercised on a treadmill for 30-40 min/d for 4 day/wk/4 wks. Blood samples
      were drawn at rest and immediately after the last exercise training. Plasma
      concentration of creatine kinase (CK), myoglobin (Mb), glutamine, and uric acid
      (UA) as biomarkers of muscle stress were measured. The results indicate that
      following the exercise program, the plasma glutamine and UA increased
      significantly (p < 0.05) from pre-to post-training levels, whereas CK isoenzyme
      and Mb levels showed no changes. In conclusion, 4 weeks of endurance training
      increased concentration of plasma glutamine and UA, which might be useful in the
      monitoring of training responses in adults with ID.

PMID- 19089749
TI  - The effects of a 4-week coffeeberry supplementation on antioxidant status,
      endurance, and anaerobic performance in college athletes.
AB  - The main aim of this investigation was to evaluate the changes in total
      antioxidant capacity (TAC) and aerobic and anaerobic performance induced by
      supplementation of coffeeberry (CB) formulation for 4 weeks in college athletes.
      Twenty college athletes (14 males and 6 females) were allocated to two randomly
      assigned trials. Subjects in the CB group orally ingested capsules that contained
      CB formulation at a dose of 800 mg per day in two equal doses for 28 days, while
      subjects in the placebo (P) group ingested an equal number of identical-looking
      caps that contained cellulose. There were no changes in glucose, cholesterol, and
      lipoproteins within or between trials (p > 0.05). Total antioxidant capacity
      (TAC) was significantly higher in the CB versus P trial at the post-
      supplementation trial (1.66 +/- 0.16 vs. 1.51 +/- 0.05 mmol/L; p < 0.05). There
      were no statistically significant changes in average anaerobic power, index of
      anaerobic fatigue, maximal heart rate, blood lactate, and maximal oxygen uptake
      within or between trials (p > 0.05). Heart rate recovery (HRR) index increased
      significantly in CB group as compared with baseline level (38 +/- 4 vs. 32 +/- 5
      beats/min; p < 0.05). Blood lactate after 10 min of recovery (Lact(rec))
      significantly decreased in the CB group after supplementation protocol as
      compared with initial results (7.6 +/- 4.2 vs. 5.5 +/- 2.6 mmol/L; p < 0.05). No
      subject reported any side effects from CB or P. The results of the present study
      indicate that supplementation with a CB formulation slightly increased
      antioxidant capacity, but there were minimal effects on recovery parameters after
      exercise in college athletes.

PMID- 19089750
TI  - Club-based and non-club-based physiotherapists' views on the psychological
      content of their practice when treating sports injuries.
AB  - The aim of the present study was to explore whether there were any differences in
      the psychological content of practice between club-contracted and non-club
      contracted physiotherapists when treating sports injuries. Eighty-seven certified
      physiotherapists (non-club contracted N = 42, club contracted N = 45) from the
      United Kingdom completed a modified version of the Athletic Training and Sport
      Psychology Questionnaire (ATSPQ). Results revealed significant between-group
      differences in psychological skills use and the importance of psychological
      skills knowledge. Non-club-contracted physiotherapists reported a higher use of
      improving social support and higher-order psychological skills (e.g., reducing
      depression, stress, and anxiety) and rated knowledge of these psychological
      skills to be more important whilst club-contracted physiotherapists reported a
      higher use of short-term goal settings. These findings suggest that non-club
      based physiotherapists may approach the treatment of injured athletes in a
      different way to their club-based counterparts. Results suggest athletes treated
      outside of the club system may experience a different recovery process.

PMID- 19089751
TI  - Does physical inactivity in children transcend educational background and
      physical ability?

PMID- 19089752
TI  - Temporary circulatory support with extra corporeal membrane oxygenation in adults
      with refractory cardiogenic shock.
AB  - OBJECTIVE: Early and long-term survival in patients suffering from cardiogenic
      shock is poor. Treatment with mechanical assist devices is complicated and
      expensive but claim to improve survival. We reviewed our experience of
      venoarterial extracorporeal membrane oxygenation (ECMO) in patients with acute
      cardiogenic shock. DESIGN: ECMO was used in 52 patients with cardiogenic shock.
      They were divided into those not operated upon previously (n=19) and those having
      had cardiac surgery prior to circulatory collapse (n=33). RESULTS: Twenty-six
      patients were weaned from ECMO. Early mortality for all patients was 48%.
      Mortality beyond 30 days was 5.8%, with no mortality in the non-cardiotomy group.
      Long-term survival for patients in the non-cardiotomy group was 63%, as compared
      to 33% in post-cardiotomy patients (p=0.07). Age over 55 years, female gender or
      cannulation site did not appear to influence survival. CONCLUSION: Mortality for
      patients in cardiogenic shock is very high. Treatment with ECMO in patients with
      refractory cardiogenic shock can be performed with good survival especially in
      non-surgical patients.

PMID- 19089753
TI  - Variation in the vascular endothelial growth factor gene, carotid intima-media
      thickness and the risk of acute myocardial infarction.
AB  - BACKGROUND: Vascular endothelial growth factor (VEGF) is a potent angiogenic
      growth factor, but its role in atherogenesis is still unclear. Our goal was to
      study whether three variants of the VEGF gene, previously associated with VEGF
      production, are linked to atherosclerosis defined as carotid intima-media
      thickness (IMT) and as the risk of acute myocardial infarction (AMI). MATERIAL
      AND METHODS: Three VEGF gene single nucleotide polymorphisms (SNPs) (-2578A>C
      rs699947, -634C>G rs2010963 and +936C>T rs3025039) were genotyped in 516 control
      subjects of the OPERA (Oulu Project Elucidating Risk of Atherosclerosis) cohort
      and in 251 survivors of AMI. In the OPERA cohort, the genotyped SNPs were
      analysed for their association with IMT. The SNPs were also analysed for their
      association with the risk of AMI, a complication of advanced atherosclerosis. In
      addition, haplotype frequencies and their associated effects on IMT and on the
      risk of AMI were estimated. RESULTS: None of the single genotyped polymorphisms
      was significantly associated with overall IMT or with the risk of AMI. However,
      the haplotype CCC was associated with higher overall IMT without plaques in women
      (p = 0.01, haplotypic effect +0.03 mm), the haplotype CCT with higher IMT without
      plaques in the internal carotid artery in men (p = 0.001, +0.11), while the
      haplotype AGT was associated with reduced AMI risk (p = 0.015, OR = 0.46).
      CONCLUSIONS: Variation in the VEGF gene is weakly associated with IMT and the
      risk of AMI, but the effect can only be observed when the information of the SNPs
      is combined by constructing haplotypes.

PMID- 19089754
TI  - Low gastric acid and high plasma gastrin in high-anxiety Wistar Kyoto rats.
AB  - OBJECTIVE: Wistar Kyoto (WKY) rats are more susceptible to stress-evoked
      ulcerations than Sprague-Dawley (SPD) rats. We have already demonstrated that
      gastrin cells are more active and ghrelin cells less active in WKY rats than in
      SPD rats. The purpose of this study was to compare endocrine cell activity and
      gastric acid output in WKY and SPD rats. MATERIAL AND METHODS: Gastric acid
      output was determined in conscious rats with gastric fistula. Plasma gastrin and
      ghrelin levels were measured after an overnight fast. Acid secretagogues
      (gastrin, histamine and carbachol) were given by continuous subcutaneous
      infusion. RESULTS: The volume of gastric juice, and the acidity and acid output
      were all significantly lower (p <0.05) in fasted WKY rats than in fasted SPD
      rats. Gastrin evoked a 4-fold (p <0.01) and 3-fold (p <0.05) increase in gastric
      acid output in SPD rats and WKY rats, respectively. Histamine raised the acid
      output 1.6-fold in SPD rats (p=0.06) and 3-fold in WKY rats (p <0.05), while
      carbachol failed to affect the acid output (weak increase, p >0.05). Fasting
      plasma ghrelin levels were 2-fold higher in SPD rats than in WKY rats (p <0.01)
      while fasting gastrin levels were 10-fold higher in WKY rats than in SPD rats (p
      <0.05). Neither the parietal-cell density nor the oxyntic mucosal thickness
      differed between the two strains. CONCLUSIONS: The results of the present study
      suggest that a high gastrin cell activity in WKY rats is secondary to a low
      gastric acidity. Whether the high gastrin cell activity is linked to
      susceptibility to stress ulcer in WKY rats warrants further investigation.

PMID- 19089756
TI  - Esotropias that totally resolve under general anesthesia treated exclusively with
      bilateral fadenoperation.
AB  - PURPOSE: Fadenoperation has been proven to be an efficient method to treat
      convergence excess because it treats medial rectus (MR) overaction. We wanted to
      evaluate its efficiency in esotropias that totally disappear under anesthesia,
      regardless of the amount of deviation in waking hours. METHODS: Included were 122
      successive cases of children of ages 3 to 16 years with esotropia that completely
      disappears under general anesthesia (GA), representing 26.25% of all patients
      with esotropia that had surgery between August 2002 and July 2004. They all
      received a fadenoperation (retroequatorial strapping) of both MR without
      recession with a 5/0 nylon suture. RESULTS: Patients were evaluated between 27
      and 51 months postoperatively. Mean initial deviation was 21 prism dioptres (PD)
      at distance and 31 PD at near fixation. Of the 122 cases, 102 (83.6%) showed
      stable postoperative deviation between +8 and -8 PD, 7 showed exotropias (< 20
      PD), and 13 showed esotropias (< 20 PD). These results were found without
      correlation to preoperative angle of deviation, ametropia, age at surgery, or
      association with vertical surgery. CONCLUSION: Our results suggest that
      fadenoperation of MR is an option to treat esotropias that disappear under
      anesthesia. The retroequatorial strapping we use seems safer than classical
      fadenoperation. We believe that the position of the eyes under GA should be
      considered for the surgical approach of esotropias.

PMID- 19089757
TI  - Quantifying vertical angle kappa after macular translocation surgery: a new use
      for the synoptophore.
AB  - PURPOSE: To report the measurement of vertical angle kappa and its application in
      patients after full macular translocation (MT360) and extraocular muscle surgery
      (to correct the resultant large angle torsion), in a prospective study. METHODS:
      A custom slide was designed to quantify vertical angle kappa using the
      synoptophore. The measurement of the vertical angle kappa was performed in the
      eye that had the MT360, after the macular translocation surgery, extraocular
      muscle surgery (to correct torsion), and silicone oil removal, all in the same
      translocated eye. Information gathered included demographic, visual acuity,
      ocular motility, torsion, past ocular history, and synoptophore examination.
      RESULTS: Fifty-three subjects met the inclusion criteria (patients who underwent
      upward MT360, with silicone oil tamponade and extraocular muscle surgery from
      3/1999 to 6/2003, and who had visual acuity better than 20/200). Twenty-nine of
      these subjects were able to complete angle kappa measurement. The mean vertical
      angle kappa was 4.6 +/- 1.4 degrees (n = 29) measured after MT360 and extraocular
      muscle surgery. The magnitude of vertical angle kappa did not correlate with
      either the amount of torsion after MT360, or the limitation of eye movement after
      both MT360 and extraocular muscle surgery. CONCLUSIONS: Vertical angle kappa can
      be measured using the synoptophore, and is increased above normal in eyes after
      MT360 and extraocular muscle surgery.

PMID- 19089759
TI  - Intermittent esotropia.
AB  - Not even half the number of the patients included in this study (N = 46) had been
      noticed as intermittent. Diplopia (N = 5) is not a reliable criterium. They need
      surgery with comparatively large amounts, on which behalf we prefer bi-medial
      rectus recessions. The prevailing result is "subnormal binocular vision," not to
      be confused with microtropia. Only four patients reached a cure, which means that
      they could not be differentiated from unaffected individuals any more.

PMID- 19089760
TI  - Long-term application of computer-based pleoptics in home therapy: selected
      results of a prospective multicenter study.
AB  - INTRODUCTION: The paper presents selected results of a prospective multicenter
      study. The reported study was aimed at the evaluation of a software-based
      stimulation method of computer training applied in addition to occlusion as a
      complementary treatment for therapy-resistant cases of amblyopia. The stimulus
      was a drifting sinusoidal grating of a spatial frequency of 0.3 cyc/deg and a
      temporal frequency of 1 cyc/sec, reciprocally coordinated with each other to a
      drift of 0.33 deg/sec. This pattern was implemented as a background stimulus into
      simple computer games to bind attention by sensory-motor coordination tasks.
      According to an earlier proposed hypothesis, the stimulation aims at the
      provocation of stimulus-induced phase-coupling in order to contribute to the
      refreshment of synchronization and coordination processes in the visual
      transmission channels. MATERIALS AND METHODS: To assess the outcome of the
      therapy, we studied the development of the visual acuity during a period of 6
      months. Our cooperating partners of this prospective multicenter study were
      strabologic departments in ophthalmic clinics and private practices as well. For
      the issue of therapy control, a partial sample of 55 patients from an overall
      sample of 198 patients was selected, according to the criterion of strong therapy
      resistance. RESULTS: The visual acuity was increased about two logarithmic steps
      by an occlusion combined with computer training in addition to the earlier
      obtained gain of the same amount by occlusion alone. Recalculated relatively to
      the duration of the therapy periods, the computer training combined with
      occlusion was found to be about twice as effective as the preceding occlusion
      alone. DISCUSSION: The results of combined computer training and occlusion show
      an additional increase of the same amount as the preceding occlusion alone, which
      yielded at its end no further advantage to the development of visual acuity in
      the selected sample of our 55 therapy-resistant patients. In a concluding
      theoretical note, a preliminary hypothesis about the neuronal mechanisms of the
      stimulus-induced treatment effect is discussed.

PMID- 19089761
TI  - Ocular prevalence: difference between crossed and uncrossed disparities of stereo
      objects.
AB  - BACKGROUND: Many observers perceive a horizontal offset between a
      stereoscopically viewed object and a reference object in the fixation plane,
      although both objects are presented along a single line that projects through the
      midpoint between both eyes. These observers weigh one eye more than the other
      when determining the visual directions of stereo objects. This unequal weighting
      has been called ocular prevalence. We considered that ocular prevalence might be
      asymmetric, that is, different for crossed and uncrossed stereo disparities.
      METHODS: We examined 11 subjects with normal eyes and a stereo resolution of less
      than 100 sec arc. A vertical line was dichoptically presented for 100 ms at
      crossed or uncrossed stereo disparities of 1, 2, 3, 4, 5, 6, or 7 min arc; this
      stereo object was judged in relation to a reference line in the fixation plane.
      RESULTS: Ten of the 11 subjects had ocular prevalence, but only 3 of the 10
      showed a significant difference between crossed and uncrossed disparities.
      CONCLUSIONS: Ocular prevalence occurs frequently among observers with normal
      binocular vision, but only a minority of these observers show a difference
      between crossed and uncrossed disparities of the stereo object. It is unclear
      whether this difference bears clinical importance.

PMID- 19089762
TI  - Computer-based simulation of the Bielschowsky head-tilt test using the SEE++
      software system.
AB  - INTRODUCTION: Latest measurements of the vestibulo-ocular reflex (VOR) allowed
      the integration of the simulation of the Bielschowsky head-tilt test (BHTT) into
      the SEE++ software system. SEE++ realizes a biomechanical model of the human eye
      in order to simulate eye motility disorders and strabismus surgeries. With the
      addition of the BHTT it can now also be used for differential-diagnostic
      simulations of complex disorders (e.g., superior oblique palsies). METHODS: In
      order to simulate the BHTT in SEE++, the user can freely choose the desired head
      tilt angle from -45 degrees to +45 degrees. The chosen angle is shown in the 3D
      view with a human body model and is also used in the calculation of the Hess
      Lancaster test. RESULTS: The integration of the BHTT offers an additional
      improvement of the possibilities for simulating eye motility disorders. Moreover,
      SEE++ allows the creation of a video of the "virtual patient" while tilting the
      head from one side to the other, which shows dynamic changes in the simulated
      Hess-diagrams. DISCUSSION: Comparisons of simulation results with patient
      measured data showed a good correlation between the simulated and the measured
      data. Further comparisons with patient data are planned.

PMID- 19089763
TI  - The origins and insertions of rectus muscles: Paul J. Tillaux and Charles B.
      Lockwood.

PMID- 19089764
TI  - P. J. Tillaux: of the way the muscles insert onto the sclera. 1877.

PMID- 19089765
TI  - C.B. Lockwood. The anatomy of the muscles, ligaments, and fasciae of the orbit,
      including an account of the capsule of Tenon, the check ligaments of the recti,
      and of the suspensory ligament of the eye. Journal of Anatomy and Physiology
      1885;20:1-25.

PMID- 19089768
TI  - Safety signals of 17-OHP-C use in pregnancy and efficacy in the prevention of
      preterm birth.

PMID- 19089769
TI  - Water aspiration syndrome at birth - report of two cases.
AB  - Under-water birth has been considered as a safe method of delivery for healthy
      women with uncomplicated pregnancies after appropriate selection of women and
      respect of hygiene rules. However, perinatal morbidity after under-water births
      is not as rare as it has been considered initially. We present the cases of two
      neonates, who were transferred to our neonatal unit during the last 12-month
      period with water aspiration after their uneventful under-water birth.

PMID- 19089770
TI  - Practice patterns in the management of isolated oligohydramnios: a survey of
      perinatologists.
AB  - OBJECTIVE: Optimal management of isolated oligohydramnios (IO) remains debatable.
      We surveyed Society for Maternal-Fetal Medicine (SMFM) members regarding their
      opinions and practice patterns. STUDY DESIGN: Questionnaires were mailed to
      perinatologists across the US. IO was defined as sonographic low fluid (per the
      practitioner's definition) in the absence of intrauterine growth restriction,
      fetal anomaly or significant maternal comorbidity. RESULTS: The overall response
      rate was 35% (n = 632). Ninety-two percent of respondents consider IO to be a
      risk factor for various adverse outcomes. With a favourable cervix, 34% and 82%
      would consider inducing labour without documented lung maturity prior to 37 and
      39 weeks, respectively. When asked whether induction of labour in cases of IO
      reduces perinatal morbidity, 45% were unsure and 21.4% thought it would not. Only
      33% believe induction could decrease adverse outcomes. Newer members of SMFM (<10
      years) and those of private practice were more likely to believe that induction
      is efficacious in decreasing morbidity. CONCLUSION: There is significant
      divergence regarding the management of IO. Despite being unsure of its benefit,
      most practitioners lean towards intervention. The available literature is
      insufficient to make firm recommendations supporting intervention for IO.

PMID- 19089771
TI  - Lysophosphatidylcholine induces endothelial cell injury by nitric oxide
      production through oxidative stress.
AB  - OBJECTIVE: To determine whether lysophosphatidylcholine (LPC) induces endothelial
      cell injury by altering the production of nitric oxide (NO) and thereby
      increasing reactive oxygen species (ROS). METHODS: Human umbilical vein
      endothelial cells (HUVECs) were cultured and exposed to LPC, LPC with N(G)-nitro
      l-arginine methyl ester (L-NAME), LPC with antioxidants. LPC-induced cell injury
      and viability were determined using LDH and Resazurin assays. The Mann-Whitney U
      test was used for statistical analysis. RESULTS: LPC induced HUVEC injury in a
      concentration-dependent manner. LPC induced the overproduction of NO and ROS in
      HUVECs and LPC-induced HUVEC injury is significantly inhibited by the eNOS
      inhibitor (L-NAME) and the antioxidants (p < 0.05). CONCLUSIONS: These findings
      suggest that LPC induces the overproduction of NO, which may increase the
      oxidative stress on endothelial cells and lead to endothelial cell injury.

PMID- 19089773
TI  - Impact of timing of antenatal corticosteroid exposure on neonatal outcomes.
AB  - OBJECTIVE: To evaluate morbidities among neonates with a history of remote
      antenatal corticosteroid (ACS) exposure compared to those with recent exposure.
      STUDY DESIGN: This is a retrospective-cohort study of neonates born at 30-33 6/7
      weeks gestational age. The primary outcome was newborn respiratory distress
      syndrome (RDS) defined by the persistent need for oxygen at 24 h of life.
      Maternal chart review established timing of ACS exposure. Data were stratified by
      the time interval of ACS administration to delivery: none or <48 h
      (Incomplete/Unexposed), 48 h to 7 days (Recent) and >7 days (Remote). Perinatal
      outcomes were compared between groups. RESULTS: Five hundred and twenty-four
      infants were included: 273 Incomplete/Unexposed, 120 Recent and 131 with Remote
      ACS exposure. RDS was significantly less frequent with Recent vs. Remote exposure
      (RR: 1.73 [1.01-3.02]p = 0.04). This finding persisted in a logistic regression
      model. CONCLUSIONS: Infants delivering more than 1 week after ACS exposure have a
      higher frequency of RDS than those who deliver within 1 week.

PMID- 19089772
TI  - Reference charts for weight gain and body mass index during pregnancy obtained
      from a healthy cohort.
AB  - OBJECTIVE: To create reference charts for weight gain and body mass index (BMI)
      in pregnancy derived from longitudinal data obtained in a representative sample
      of the Argentinean population. METHODS: A prospective cohort of 1439 healthy
      pregnant women was selected from antenatal clinics in seven different urban
      regions in Argentina. Serial anthropometric measurements were made at weeks 12,
      16, 20, 24, 28, 32, 36 and in the last pre-natal control. Centile curves of body
      weight and BMI by gestational age were developed using the LMS method. RESULTS:
      Mean weight gain at 38 weeks of gestation was 11.9 +/- 4.4 kg. There were no
      differences in total weight gain between women who enter pregnancy with low,
      normal or overweight; only those women with a pre-pregnancy BMI in the range of
      obesity showed a significantly lower weight gain (10.2 +/- 4.8 kg). At 12 weeks
      of pregnancy, BMI values of the 10th, 50th and 90th centiles were 19.3, 22.8 and
      29.0, and at 38 weeks these values were 23.3, 27.4 and 33.8, respectively.
      CONCLUSION: This BMI for gestational age chart, based on women who delivered
      normal birth weight infants and processed with modern statistical methods,
      represents an improvement in pre-natal care monitoring.

PMID- 19089774
TI  - Lipid peroxidation in nuchal cord cases: implication for fetal distress.
AB  - OBJECTIVE: To examine whether nuchal cord affects fetal lipid peroxidation and
      cord arterial blood gases, and thus to determine whether lipid peroxidation can
      show intrapartum distress. METHODS: Pregnant women giving birth to a baby with
      nuchal cord (n = 32) formed the study group and others without this condition
      made up the control group (n = 36). The maternal malondialdehyde levels (MDA)
      before and after delivery as well as fetal umbilical cord MDA and arterial blood
      gases were measured in both the groups. RESULTS: Mean cord MDA level was higher
      in the study group (p < 0.02) and was significantly higher than maternal MDA
      level after birth within the same group (p = 0.007). Cord blood gases as well as
      neonatal and labour characteristics showed no difference, except for variable
      decelerations, which were 2.2 times more common in the study group. Correlations
      between maternal MDA levels before and after delivery, umbilical cord MDA and
      arterial blood gases were non-significant in the nuchal cord group. CONCLUSIONS:
      During delivery, nuchal cord increases lipid peroxidation without causing
      significant fetal acidemia. Level of lipid peroxidation may be a more sensitive
      indicator of intrapartum distress than results of acid-base studies.

PMID- 19089775
TI  - The correlation in birth timing between singleton and twin gestations in the same
      mother.
AB  - OBJECTIVE: To test the hypothesis that the timing of twin births is correlated to
      that of their singleton siblings. METHODS: Using the Missouri Department of
      Health's birth certificate database we performed a retrospective population-based
      cohort study of 2222 women who had at least one singleton and one twin birth
      (1989-1997). Pearson correlation analysis was conducted to examine the
      relationship in gestational age between singleton and twin births occurring in
      the same mother. RESULTS: Among 2222 mothers who had both a singleton and twin
      pregnancy during the study period, the mean difference in birth timing between
      singleton and twin siblings was 3.05 weeks (+/-2.9 weeks). The correlation
      between singleton and twin birth timing was statistically significant (r = 0.28,
      p < 0.001), and remained significant even after controlling for potential
      confounders (beta = 0.459, p < 0.001). CONCLUSIONS: We identified a significant
      correlation in the timing of birth between singleton and twin pregnancies in the
      same mother, which could be due to shared genetic, environmental, medical, social
      and other influences. This finding could be useful to help predict birth timing
      in mothers at especially high risk of preterm birth, those with a twin gestation.

PMID- 19089776
TI  - Use of diazepam for hyperemesis gravidarum.
AB  - OBJECTIVE: To evaluate the efficacy and safety of intravenous (IV) fluid and
      diazepam therapy compared with the IV-fluid only therapy for the resistant
      hyperemesis gravidarum (HG) cases. METHODS: Medical records of 74 HG cases who
      were refractory to standard management were reviewed. All patients hospitalised
      were administered IV fluid and multivitamin combination as the first-step
      therapy. Patients who were refractory to first-step therapy were given IV fluid
      (Group 1, n = 43) or IV fluid and diazepam (Group 2, n = 31) depending on the
      patients' desire. Groups were matched for demographic characteristics,
      rehospitalisation requirement, patient satisfaction and neonatal outcomes.
      RESULTS: Thirteen of the 74 patients were excluded from the study because of
      unknown maternal and fetal outcome. The mean gestational age was 10.4 +/- 2.4
      year. Age, parity, body mass index and educational level were similar between the
      two groups. Mean diazepam dose was 62.8 +/- 24.5 mg (range 40-160) in Group 2 (n
      = 31). The number of hospitalisation was significantly lower, and patient
      satisfaction was significantly higher in Group 2. There were no differences for
      the obstetrics outcomes between the groups. CONCLUSIONS: The addition of diazepam
      to IV fluids was associated with less hospitalisation in women with hyperemesis
      gravidarum. Safety of diazepam therapy in early pregnancy deserves further study.

PMID- 19089777
TI  - Side effects of oral misoprostol for the prevention of postpartum hemorrhage:
      results of a community-based randomised controlled trial in rural India.
AB  - OBJECTIVE: To investigate the side effects of 600 microg oral misoprostol given
      for the mother and the newborn to prevent postpartum hemorrhage (PPH). METHODS:
      One thousand six hundred twenty women delivering at home or subcentres in rural
      India were randomised to receive misoprostol or placebo in the third stage of
      labour. Women were evaluated for shivering, fever, nausea, vomiting and diarrhea
      at 2 and 24 h postpartum. Newborns were evaluated within 24 h for diarrhea,
      vomiting and fever. Symptoms were graded as absent, mild-to-moderate or severe.
      RESULTS: Women who received misoprostol had a significantly greater incidence of
      shivering (52%vs. 17%, p < 0.001) and fever (4.2%vs. 1.1%, p < 0.001) at 2 h
      postpartum compared with women who received placebo. At 24 h, women in the
      misoprostol group experienced significantly more shivering (4.6%vs. 1.4%, p <
      0.001) and fever (1.4%vs. 0.4%, p < 0.03). There were no differences in nausea,
      vomiting or diarrhea between the two groups. There were no differences in the
      incidence of vomiting, diarrhea or fever for newborns. CONCLUSIONS: Misoprostol
      is associated with a significant increase in postpartum maternal shivering and
      fever with no side effects for the newborn. Given its proven efficacy for the
      prevention of PPH, the benefits of misoprostol are greater than the associated
      risks.

PMID- 19089778
TI  - Pregnancy-associated colon and rectal cancer: perinatal and cancer outcomes.
AB  - OBJECTIVE: Assess the impact of colorectal cancer on maternal and neonatal
      outcomes. METHODS: Cases were identified using several computer-generated linkage
      analyses. Maternal and newborn hospital discharges in California were linked to
      birth and if applicable infant death certificate records. This database was then
      linked to the California Cancer Registry, to create a cohort of women with
      pregnancy-associated colon and rectal cancer. This cohort was compared to
      pregnant women in California without colorectal cancer. Our secondary comparison
      was to non-pregnant, Californian women with colorectal cancer who could be aged
      matched. RESULTS: Women with pregnancy-associated colorectal cancer were more
      likely to undergo cesarean section (OR: 1.9) and to develop puerperal infections
      (OR: 2.8). In addition, higher rates of preterm delivery were found both
      secondary to scheduled deliveries and preterm labor (OR for preterm labor, 2.8).
      Neonatal outcomes were fairly similar between the two groups. Pregnancy was not
      found to have a significant effect on survival (HR: 0.73). CONCLUSIONS: We found
      that women with pregnancy-associated colorectal cancer had excellent maternal and
      neonatal outcomes. This is likely secondary to the fact that most women are
      diagnosed after delivery. In addition, survival is similar between pregnancy
      associated and non-pregnancy associated cases.

PMID- 19089780
TI  - A new device (cicogna) for transferring the neonate in the delivery room setting:
      a randomised, controlled trial.
AB  - OBJECTIVE: We developed a new system ('cicogna') for transferring the neonates
      into the delivery room setting. Our aim was to compare the 'cicogna' system and
      the conventional method (plastic basin) with regard to the time needed to
      transfer the neonate from the operating table to the radiant warmer; and to
      evaluate the degree of approval for the 'cicogna' expressed by the midwives.
      STUDY DESIGN: In a prospective, randomised, controlled trial including 100
      infants (gestational age > or =34 weeks), we measured the time elapsed from the
      umbilical cord clamping to the positioning of the neonate under the radiant
      warmer using the 'cicogna' system or the conventional method. Midwives involved
      in the study were asked to fill out a final, written evaluation regarding the
      feasibility and the safety of the devices. RESULTS: The time elapsed from the
      cord clamping to the positioning of the infant under the radiant warmer was
      significantly shorter for infants who were managed with the 'cicogna' system
      compared with infants who received standard care: 18.7 +/- 5.6 s vs. 24.5 +/- 9.0
      s (p < 0.001). In the evaluation forms, 19 out of 20 midwives (95%) evaluated the
      'cicogna' as good or excellent. CONCLUSIONS: In comparison with the conventional
      method, 'cicogna' decreased the time needed to transfer the neonate into delivery
      room setting and received a high degree of approval by personnel involved in
      neonatal care. It appears to be a feasible and safe method for transferring the
      neonate in the setting of the delivery room.

PMID- 19089779
TI  - Stillbirth in developing countries: a review of causes, risk factors and
      prevention strategies.
AB  - OBJECTIVE: To understand the rates, causes and risk factors for stillbirth in
      developing countries as well as the strategies that have been evaluated to reduce
      stillbirth. METHODS: We searched the English literature for 2003-2008 for all
      articles related to stillbirth and perinatal mortality in developing countries
      and reviewed all related publications. RESULTS: Despite the large number of
      stillbirths worldwide, the topic of stillbirths in developing countries has
      received very little research, programmatic or policy attention. In many
      developing countries, almost half of the deliveries occur at home, and under
      reporting of stillbirths is a significant problem. Reliable data about rates and
      causes are unavailable in many areas of the world. Nevertheless, of the estimated
      3.2 million stillbirths that occur yearly world-wide, the vast majority occur in
      developing countries. Rates in many developing countries are 10-fold greater or
      more than in developed countries. There is not a standard international
      classification system that defines cause of death, nor is there agreement about
      the lower limits of birthweight or gestational age that define stillbirth, making
      comparisons of causes of stillbirth or rates over time or between sites
      problematic. From available data, prolonged and obstructed labour, pre-eclampsia
      and various infections, all without adequate treatment, appear to account for the
      majority of stillbirths in developing countries. Identification and treatment of
      maternal syphilis has been effective in reducing stillbirth risk, as has
      improvements in access to emergency obstetrical services and particularly
      caesarean section. CONCLUSIONS: Further research is needed to understand the
      causes and the best preventive strategies for stillbirth specific to geographic
      areas. However, based on current data, better access to appropriate obstetric
      care, particularly during labour and delivery and better screening and treatment
      of syphilis should reduce developing country stillbirth rates dramatically.

PMID- 19089781
TI  - Uterine necrosis following selective embolization for postpartum hemorrhage using
      absorbable material.
AB  - Embolization of the uterine arteries with resorbable material is an effective
      treatment for postpartum hemorrhage. Cases of uterine necrosis were already
      described but with non-resorbables particles. We report two exceptional cases of
      uterine necrosis with failure of conservative treatment following selective
      embolization with gelatine.

PMID- 19089782
TI  - Pregnancy outcome after ovulation induction with aromatase inhibitors or
      clomiphene citrate in unexplained infertility.
AB  - OBJECTIVE: To evaluate the pregnancy outcome after ovulation induction with
      aromatase inhibitors or clomiphene citrate (CC). DESIGN: A prospective,
      randomized, controlled trial. SETTING: A university hospital center and a private
      practice setting. POPULATION: The study comprised a total of 796 infertile women
      (1,100 cycles) and 200 spontaneously pregnant women (298 cycles) as a control
      group. METHODS: Patients were allocated treatment either with 100 mg of CC daily
      (420 patients, 634 cycles), 5 mg of letrozole daily (269 patients, 323 cycles) or
      1 mg of anastrozole daily (107 patients, 143 cycles) for 5 days starting on day 3
      of menses. MAIN OUTCOME MEASURES: The occurrence of pregnancy, miscarriage and
      neonatal condition. RESULTS: Pregnancy occurred in 167/1,398 cycles (11.9%) in
      total without significant differences between groups. The total miscarriage rate
      was 16.1% (varied between 14.2% in CC group and 19.9% in anastrozole group)
      without difference between spontaneous and stimulated pregnancies. There were 129
      deliveries in all groups. There were no significant differences between the
      stimulated and spontaneous pregnancies as regards mean gestational age, premature
      deliveries, birth weight, SGA<10th percentile or five minutes Apgar score. There
      was one case of complete cleft palate and one case of major congenital heart
      problem in the letrozole group. There were two cases of talipus equinovarus in
      the CC and spontaneous pregnancy group. CONCLUSION: Aromatase inhibitors and CC
      resulted in favorable pregnancy outcomes and average miscarriage rates. Safety of
      the drugs for both the mother and fetuses was documented.

PMID- 19089783
TI  - Relation between vaginal birth and pelvic organ prolapse.
AB  - OBJECTIVE: To evaluate the relation between vaginal birth and pelvic organ
      prolapse quantification (POPQ) stages III and IV prolapse and whether each
      additional vaginal birth is associated with an increase in pelvic support
      defects. DESIGN: Prospective cross-sectional study. SETTING: Gynecology clinic in
      a University Hospital. POPULATION: Four hundred and fifty-eight nulliparas and
      892 multiparas, including 272 with one, 299 with two and 321 with at least three
      term vaginal deliveries. METHODS: In a Human Investigation Committee approved
      study, the pelvic support of nulliparas and multiparas who only had term vaginal
      deliveries was evaluated for prolapse using the POPQ system. MAIN OUTCOME
      MEASURE: 1. Difference in POPQ stages III and IV prolapse between nulliparas and
      multiparas. 2. Difference in POPQ stage distribution among nulliparas and
      multiparas who had one, two, and at least three term vaginal deliveries. RESULTS:
      Compared with nulliparas, the odds ratios of having POPQ stage II defect and
      stage III or IV prolapse associated with multiparas was 2.95 (95% CI: 2.06-4.24)
      and 1.01 (95% CI: 0.40-2.79), respectively. The prevalence of POPQ stage II
      defect among nulliparas and multiparas that had one, two, and at least three term
      vaginal deliveries was 25% (119/458), 50% (137/272), 66% (198/299), and 69%
      (220/321), respectively (p<0.001), while 1% (6/458), 1% (4/272), 2% (7/299), and
      2% (8/321), respectively, had POPQ stage III or IV prolapse (p=0.618).
      CONCLUSIONS: Vaginal birth is not associated with POPQ stages III and IV
      prolapse, but it is associated with an increase in POPQ stage II defect.

PMID- 19089785
TI  - Improving the damage accumulation in a biomechanical bone remodelling model.
AB  - We extend, reformulate and analyse a phenomenological model for bone remodelling.
      The original macrobiomechanical model (MBM), proposed by Hazelwood et al. [J
      Biomech 2001; 34:299-308], couples a population equation for the cellular
      activities of the basic multicellular units (BMUs) in the bone and a rate
      equation to account for microdamage and repair. We propose to account for bone
      failure under severe overstressing by incorporating a Paris-like power-law damage
      accumulation term. The extended model agrees with the Hazelwood et al.
      predictions when the bone is under-stressed, and allows for suitably loaded bones
      to fail, in agreement with other MBM and experimental data regarding damage by
      fatigue. We numerically solve the extended model using a convergent algorithm and
      show that for unchanging loads, the stationary solution captures fully the model
      behaviour. We compute and analyse the stationary solutions. Our analysis helps
      guide additional extensions to this and other BMU activity based models.

PMID- 19089787
TI  - Drosophila mutants in phospholipid signaling have reduced olfactory responses as
      adults and larvae.
AB  - In this paper, we show that mutants in the gene stambhA (stmA), which encodes a
      putative phosphatidylinositol 4,5 bisphosphate-diacylglycerol lipase, exhibit a
      significant reduction in the amplitudes of odor-evoked responses recorded from
      the antennal surface of adult Drosophila. This lends support to previously
      published findings that olfactory transduction in Drosophila requires a
      phospholipid intermediate. Mutations in stmA also affect the olfactory behavior
      response of larvae. Moreover, there is a requirement for G(q)alpha and
      phospholipase Cbeta function in larval olfaction. The results suggest that larval
      olfactory transduction, like that of the adult, utilizes a phospholipid second
      messenger, generated by the activation of G(q)alpha and Plcbeta21c, and modulated
      by the stmA gene product.

PMID- 19089788
TI  - Central nervous system complications following Hanta virus cardiopulmonary
      syndrome.

PMID- 19089789
TI  - Interactions between gastric acid secretagogues and the localization of the
      gastrin receptor.

PMID- 19089790
TI  - Association of polymorphism of the p22PHOX component of NADPH oxidase in
      gastroduodenal diseases in Japan.
AB  - OBJECTIVE: Superoxide has been implicated in the pathogenesis of Helicobacter
      pylori-related diseases through inflammation. NADPH oxidase, a major source of
      superoxide generation, plays a critical role in H. pylori-related gastric
      inflammation. The aim of this study was to clarify the effect of the p22PHOX
      C242T polymorphism, an essential component of NADPH oxidase in the risk of
      gastroduodenal diseases, on the severity of H. pylori-induced gastritis in a
      Japanese population. MATERIAL AND METHODS: The study comprised 436 patients
      attending the Endoscopy Center of Fujita Health University Hospital. The p22PHOX
      C242T polymorphism was determined by polymerase chain reaction-restriction
      fragment length polymorphism (PCR-RFLP). Gastritis scores of antral gastric
      mucosa were assessed according to the updated Sydney system. RESULTS: The 436
      patients represented 106 gastric ulcers (24.3%), 48 duodenal ulcers (11.0%), and
      282 non-ulcer subjects (64.7%). No association was found between p22PHOX
      polymorphism and the risk of ulcer diseases compared to non-ulcer subjects.
      However, among H. pylori-positive subjects, the degree of intestinal metaplasia
      tended to be lower in 242T carriers aged more than 60 years (p=0.0488). The same
      allele also decreased the risk of developing a more severe intestinal metaplasia
      in H. pylori-positive female subjects (p=0.0441). CONCLUSIONS: Our data suggest
      that the p22PHOX 242T allele is associated with a reduced risk of developing a
      more severe intestinal metaplasia in subjects older than 60 years of age and in
      female subjects with H. pylori infection.

PMID- 19089792
TI  - [Responsibility for timely assessment of findings (OLG Zweibrucken, Urteil v. 24.
      4. 2007, Az. 5 U 2/06)--compensation for delayed report of findings].

PMID- 19089793
TI  - Sleep disorders in dialysis patients.
AB  - Poor sleep and sleep-related breathing disorders are common in patients with end
      stage renal disease (ESRD) but are often unrecognized and undertreated. Sleep
      disorders are known negative prognostic factors for morbidity and mortality. The
      most frequent sleep disorders seen in patients with ESRD are conditioned
      insomnia, excessive daytime sleepiness, obstructive or central sleep apnea (SA),
      as well as restless legs syndrome (RLS) and periodic limb movement disorder
      (PLMD). Several uremic and nonuremic factors are thought to participate in the
      pathogenesis of sleep disorders in patients with ESRD. The therapy of sleeping
      disorders includes nonpharmacological and pharmacological measures that can
      improve the functionality and quality of life in patients with ESRD.

PMID- 19089794
TI  - Optimized convective transport with automated pressure control in on-line
      postdilution hemodiafiltration.
AB  - PURPOSE: In a stable patient population we evaluated on-line postdilution
      hemodiafiltration (HDF) on the incremental improvement in blood purification
      versus high-flux HD, using the same dialyzer and blood flow rate. For HDF we used
      a new way of controlling HDF treatments based on the concept of constant pressure
      control where the trans-membrane pressure is automatically set by the machine
      using a feedback loop on the achieved filtration (HDF UC). METHODS: We enrolled
      20 patients on on-line HDF treatment and during a 4-week study period recorded
      key treatment parameters in HDF UC. For one mid-week study treatment performed in
      HD and one midweek HDF UC treatment we sampled blood and spent dialysate to
      evaluate the removal of small- and middle-sized solutes. RESULTS: We achieved
      18+/-3 liters of ultrafiltration in four-hour HDF UC treatments, corresponding to
      27+/-3% of the treated blood volume. That percentage varied by patient hematocrit
      level. The ultrafiltration amounted to 49+/-4% of the estimated plasma water
      volume treated. We noted few machine alarms. For beta2m and factor D the
      effective reduction in plasma level by HDF (76+/-6% and 43+/-9%, respectively)
      was significantly greater than in HD, and a similar relation was seen in mass
      recovered in spent dialysate. Small solute removal was similar in HDF and HD.
      Albumin loss was low. CONCLUSION: The additional convective transport provided by
      on-line HDF significantly improved the removal of middle molecules when all other
      treatment settings were equal. Using the automated pressure control mode in HDF,
      the convective volume depended on the blood volume processed and the patient
      hematocrit level.

PMID- 19089795
TI  - Continuous veno-venous hemofiltration with regional citrate anticoagulation: a
      four-year single-center experience.
AB  - BACKGROUND: Hemofiltration protocols using a citrate-buffered replacement
      solution offer the advantage of regional anticoagulation and a buffer effect. The
      role played by such fluids in clinical practice is not yet well established. The
      risk of electrolytic disorders, acid-base imbalance, or citrate accumulation
      should be clarified. We report on a renal therapy protocol based on a citrate
      isonatremic replacement solution. METHOD: We considered all patients needing
      renal replacement therapy admitted to our cardiovascular intensive care unit
      between January 2003 and June 2007. A citrate-buffered fluid was delivered in
      predilution mode to a post-filter ionized calcium target < or = 0.25 mmol/L.
      Extracorporeal blood flow was set at a constant of 140+/-10 ml/min. Blood
      calcemia was maintained by a 5% calcium-chloride solution infused into the
      patient. We recorded the patients' acid-base variables, ionized calcium, daily
      electrolytes, albumin, urea and filter life-span. RESULTS: We observed 101
      consecutive patients out of 2,523; incidence 4%, overall mortality was 57% at ICU
      discharge. Mean replacement rate was 2,554+/-475 ml/h corresponding to 34+/-5
      ml/kg/h. Mean patient ionized calcium level was 1.07+/-0.04 mmo/L, maintained by
      13+/-2 ml/h of infused calcium-chloride. All other electrolytes remained in the
      normal range. The Stewart biophysical approach confirmed a strong anion gap of
      3.1+/- 3 meq/L. Acid-base balance showed a buffer effect. Mean filter life-span
      was 52+/-11 h. CONCLUSION: Renal replacement therapy based on citrate-buffered
      fluid may be useful in clinical practice. This methodology presented an adequate
      metabolic control and allowed regional anticoagulation. A sufficient calcium
      supply was mandatory to avoid hypocalcemia. The small strong ion gap suggested a
      modest citrate accumulation.

PMID- 19089796
TI  - Effect of fiber structure on dialysate flow profile and hollow-fiber hemodialyzer
      reliability: CT perfusion study.
AB  - BACKGROUND: Uniform dialysate distributions in hollow-fiber hemodialyzers
      facilitate effective solute removal, and the fiber structure inside hemodialyzers
      plays a significant role in determining dialysate flow distribution and dialysis
      efficiency. The authors analyzed the effects of undulated fibers on dialysate
      flow profiles and hemodialyzer reliability using a perfusion CT technique.
      METHOD: Using a multi-detector row CT unit, perfusion studies were performed on
      two different types of hemodialyzers: (A) straight fiber configuration; (B)
      undulated fiber configuration (wavy-shaped fibers). Deconvolution theory was used
      for image processing to derive dialysate flows, dialysate volumes, and mean
      transit time distributions. Three-dimensional perfusion maps for the two types of
      hemodialyzers were reconstructed using high resolution images and these
      parameters were compared at hemodialyzer midsections. RESULTS: Dialysate
      maldistributions were observed in both types of hemodialyzer. However, dialysate
      flow distributions were more uniform in the undulated-fiber hemodialyzer, whereas
      more complex flow distributions developed in straight-fiber hemodialyzer.
      Reliability as determined using intraclass correlation coefficients was markedly
      higher for the hemodialyzer containing undulated fiber (0.968 vs. 0.496 for type
      A and type B, respectively). CONCLUSIONS: The undulated-fiber type was found to
      have more uniform, consistent dialysate flow profiles. It is believed that this
      type of hemodialyzer will be found helpful for measurement and prescription of
      the delivered hemodialysis dose due to its better consistency.

PMID- 19089797
TI  - TGFbeta-1 and epithelial-mesenchymal interactions promote smooth muscle gene
      expression in bone marrow stromal cells: possible application in therapies for
      urological defects.
AB  - PURPOSE: For regenerative and cellular therapies of the urinary tract system,
      autologous bladder smooth muscle cells (SMCs) have several limitations, including
      constricted in vitro proliferation capacity and, more importantly, inability to
      be used in malignant conditions. The use of in vitro (pre-)differentiated
      multipotential adult progenitor cells may help to overcome the shortcomings
      associated with primary cells. METHODS: By mimicking environmental conditions of
      the bladder wall, we investigated in vitro effects of growth factor applications
      and epithelial-mesenchymal interactions on smooth muscle gene expression and on
      the morphological appearance of adherent bone marrow stromal cells (BMSCs).
      RESULTS: Transcription growth factor beta-1 (TGFbeta-1) upregulated the
      transcription of myogenic gene desmin and smooth muscle actin-gamma2 in cultured
      BMSCs. Stimulatory effects were significantly increased by coculture with
      urothelial cells. Prolonged stimulation times and epigenetic modifications
      further enhanced transcription levels, indicating a dose-response relationship.
      Immunocytochemical staining of in vitro-differentiated BMSCs revealed expression
      of myogenic protein alpha-smooth muscle actin and desmin, and changes in
      morphological appearance from a fusiform convex shape to a laminar flattened
      shape with filamentous inclusions similar to the appearance of bladder SMCs. In
      contrast to the TGFbeta-1 action, application of vascular endothelial growth
      factor (VEGF) did not affect the cells. CONCLUSIONS: The combined application of
      TGFbeta-1 and epithelial-mesenchymal interactions promoted in vitro outgrowth of
      cells with a smooth muscle-like phenotype from a selected adherent murine bone
      marrow-derived cell population.

PMID- 19089798
TI  - Recombinant human type II collagen as a material for cartilage tissue
      engineering.
AB  - PURPOSE: Collagen type II is the major component of cartilage and would be an
      optimal scaffold material for reconstruction of injured cartilage tissue. In this
      study, the feasibility of recombinant human type II collagen gel as a 3
      dimensional culture system for bovine chondrocytes was evaluated in vitro.
      METHODS: Bovine chondrocytes (4x106 cells) were seeded within collagen gels and
      cultivated for up to 4 weeks. The gels were investigated with confocal
      microscopy, histology, and biochemical assays. RESULTS: Confocal microscopy
      revealed that the cells maintained their viability during the entire cultivation
      period. The chondrocytes were evenly distributed inside the gels, and the number
      of cells and the amount of the extracellular matrix increased during cultivation.
      The chondrocytes maintained their round phenotype during the 4-week cultivation
      period. The glycosaminoglycan levels of the tissue increased during the
      experiment. The relative levels of aggrecan and type II collagen mRNA measured
      with realtime polymerase chain reaction (PCR) showed an increase at 1 week.
      CONCLUSION: Our results imply that recombinant human type II collagen is a
      promising biomaterial for cartilage tissue engineering, allowing homogeneous
      distribution in the gel and biosynthesis of extracellular matrix components.

PMID- 19089799
TI  - Mechanical axial flow blood pump to support cavopulmonary circulation.
AB  - We are developing a collapsible, percutaneously inserted, axial flow blood pump
      to support the cavopulmonary circulation in infants with a failing single
      ventricle physiology. An initial design of the impeller for this axial flow blood
      pump was performed using computational fluid dynamics analysis, including
      pressure-flow characteristics, scalar stress estimations, blood damage indices,
      and fluid force predictions. A plastic prototype was constructed for hydraulic
      performance testing, and these experimental results were compared with the
      numerical predictions. The numerical predictions and experimental findings of the
      pump performance demonstrated a pressure generation of 2-16 mm Hg for 50-750
      ml/min over 5,500-7,500 RPM with deviation found at lower rotational speeds. The
      axial fluid forces remained below 0.1 N, and the radial fluid forces were
      determined to be virtually zero due to the centered impeller case. The scalar
      stress levels remained below 250 Pa for all operating conditions. Blood damage
      analysis yielded a mean residence time of the released particles, which was found
      to be less than 0.4 seconds for both flow rates that were examined, and a maximum
      residence time was determined to be less than 0.8 seconds. We are in the process
      of designing a cage with hydrodynamically shaped filament blades to act as a
      diffuser and optimizing the impeller blade shape to reduce the flow vorticity at
      the pump outlet. This blood pump will improve the clinical treatment of patients
      with failing Fontan physiology and provide a unique catheter-based therapeutic
      approach as a bridge to recovery or transplantation.

PMID- 19089800
TI  - Design and performance testing of an axial-flow ventricular assist device
      developed at the Fu Wai Hospital in Beijing.
AB  - PURPOSE: Various ventricular assist devices (VADs) have been developed for
      clinical use in recent years. The aim of a multidisciplinary research team at the
      Fuwai Hospital of the Peking Union Medical College is to design and develop an
      axial flow left ventricular assist device (LVAD) for adults. METHODS: Using
      Computational Fluid Dynamics (CFD), the inflow characteristics of the axial flow
      pump were analyzed. After CFD analysis, the axial pump was fabricated using a 5
      axis, computer numerical control (CNC) milling machine. Performances of the pump
      both in vitro and in vivo were tested. RESULTS: This VAD, which was developed
      after numerous CFD analyses for the flow characteristics of the pump, is 58.5 mm
      long, 30 mm wide and weighs 120 g. The pump can deliver 5 lpm for pressures of
      100 mmHg over 8500 rpm. The NIH value was 0.01 g/100 L. The hemolysis, which was
      evaluated in an in vivo test, was a bit higher than the normal value, but
      remained within an acceptable range. CONCLUSIONS: Performance of the pump in
      vitro and in vivo was considered sufficient for an LVAD. Further design
      improvements are being undertaken in terms of hemolysis and thrombosis to improve
      the biocompatibility of the pump.

PMID- 19089801
TI  - Assessment of the efficacy and safety of low frequency, low intensity magnetic
      fields in patients after knee endoprosthesis plasty. Part 2: a clinical study.
AB  - The purpose of this clinical study was to assess low frequency, low intensity
      magnetic fields in the enhancement of the physical rehabilitation of patients
      after knee endoprosthesis surgery. The study included 62 patients who underwent
      total knee arthroplasty. Group A consisted of 32 patients who were physically
      rehabilitated. Group B consisted of 30 patients who were physically rehabilitated
      and treated additionally with pulsing magnetic fields (5 mT, 30 Hz, 20 min once a
      day, 5 days weekly). Therapy lasted 3 weeks for both groups. The rehabilitation
      process was evaluated using a goniometer, tensometer, goniometric pendulum test,
      Lysholm scale for knee function, and a visual analogue scale (VAS) questionnaire
      for pain and activity. The changes of measured rates were comparable in both
      groups. Low frequency and low intensity magnetic fields of examined parameters
      were not demonstrated to effectively improve the rehabilitation of patients after
      knee endoprosthesis surgery.

PMID- 19089802
TI  - Comment: Did undetected AC components affect a DC magnetic field experiment?
      (Vashisth A, Nagarajan S. 2008. Bioelectromagnetics 29:571-578).

PMID- 19089803
TI  - A room temperature ionic liquid as convenient solvent for the oxidative folding
      of conopeptides.
AB  - We report the first example of conopeptide oxidation performed in a biocompatible
      ionic liquid, 1-ethyl-3-methylimidazolium acetate ([C(2)mim][OAc]), which enables
      the efficient formation of both hydrophilic and poorly water-soluble conotoxins
      compared with conventional methods. Moreover, the method features a high
      concentration approach ultimately leading to higher yields at reduced separation
      effort.

PMID- 19089804
TI  - Synthesis, conformational analysis and immunological activity of beta3Phe
      substituted Cyclolinopeptide A analogues.
AB  - CLA, a natural, highly hydrophobic cyclic nonapeptide with sequence c(Pro(1)
      Pro(2)-Phe(3)-Phe(4)-Leu(5)-Ile(6)-Ile(7)-Leu(8)-Val(9)-), isolated from linseed
      oil, was found to possess a strong immunosuppressive activity comparable, in low
      doses, with that of CsA, with a mechanism that depends on the inhibition of the
      interleukin-1 and interleukin-2 action. Structural analysis of CLA and its
      related compounds has underlined that the presence of the tetrapeptide Pro-Pro
      Phe-Phe sequence, the Pro-Pro cis amide bond, and the 'edge-to-face' interaction
      are possible important features for the immunosuppressive activity of CLA. To
      evaluate the role and significance of 'edge-to-face' interaction in the process
      of molecular recognition by receptors, we have synthesised three linear
      precursors and three cyclic analogues of CLA, in which one or both Phe residues
      have been replaced by beta(3)Phe residues. A conformational analysis by NMR in
      CD(3)CN/H(2)O mixture has been carried out on the CLA analogue, in which Phe(3)
      has been replaced by a betaPhe, to study the influence of the mutation on the
      three-dimensional structure. All linear and cyclic CLA analogues containing
      betaPhe have been tested in the humoral and cellular immune response in vivo
      assays in mice. The peptide activities have been compared with CsA, as a
      reference drug.

PMID- 19089806
TI  - The relationship between socio-sexual behavior and salivary cortisol in bonobos:
      tests of the tension regulation hypothesis.
AB  - Bonobos are known for their pacifistic behavior and their large repertoire of
      behaviors that are thought to serve conflict resolution. One is an unusual form
      of ventro-ventral mounting that facilitates genital contacts (GC). Various
      hypotheses have been proposed to explain its function. In this study we tested
      predictions of the tension regulation hypothesis using salivary cortisol as a
      marker for social stress. The results indicate a temporal relationship between GC
      and cortisol levels. Compared with baseline data and matched samples of
      unrestricted food access, rates of GC increased when access to food sources was
      restricted. Cortisol levels were highest when access to food was constrained.
      However, because the behavioral and hormonal responses occurred when viewing the
      stimulus at a distance and preceded the physical presence of the stimulus, we
      conclude that the anticipation of a competitive situation was sufficient to
      induce social stress. Contrary to our prediction, targets of aggression did not
      have higher rates of GC nor did they solicit GC more often than others.
      Furthermore, higher GC rates did not correlate with a more pronounced decrease in
      cortisol levels. Not all results obtained in this study supported the predictions
      concerning the regulatory function of GC on social tension and further research
      is needed to explore this question. However, the results indicate that the
      anticipation of competition may be sufficient to induce a costly physiological
      response, and that high levels of resource competition may have lasting effects
      on physical stress and stress management.

PMID- 19089805
TI  - MAP dendrimer elicits antibodies for detecting rat and mouse GH-binding proteins.
AB  - The membrane-bound rat GH-R and an alternatively spliced isoform, the soluble rat
      GH-BP, are comprised of identical N-terminal GH-binding domains; however, their C
      terminal sequences differ. Immunological reagents are needed to distinguish
      between the two isoforms in order to understand their respective roles in
      mediating the actions of GH. Accordingly, a tetravalent MAP dendrimer with four
      identical branches of a C-terminal peptide sequence of the rat GH-BP (GH-BP(263
      279)) was synthesized and used as an immunogen in rabbits. Solid-phase peptide
      synthesis of four GH-BP(263-279) segments onto a tetravalent Lys(2)-Lys-beta-Ala
      OH core peptide was carried out using Fmoc chemistry. The mass of the RP-HPLC
      purified synthetic product, 8398 Da, determined by ESI-MS, was identical to
      expected mass. Three anti-rat GH-BP(263-279) MAP antisera, BETO-8039, BETO-8040,
      and BETO-8041, at dilutions of 10(-3), recognized both the rat GH-BP(263-279) MAP
      and recombinant mouse GH-BP with ED(50)s within a range of 5-10 fmol, but did not
      cross-react with BSA in dot blot analyses. BETO-8041 antisera (10(-3) dilution)
      recognized GH-BPs of rat serum and liver having M(r)s ranging from 35 to 130 kDa,
      but did not recognize full-length rat GH-Rs. The antisera also detected
      recombinant mouse GH-BPs. In summary, the tetravalent rat GH-BP(263-279) MAP
      dendrimer served as an effective immunogenic antigen in eliciting high titer
      antisera specific for the C-termini of both rat and mouse GH-BPs. The antisera
      will facilitate studies aimed at improving our understanding of the biology of GH
      BPs.

PMID- 19089807
TI  - Mutation screen and association analysis of the glucocorticoid receptor gene
      (NR3C1) in childhood-onset mood disorders (COMD).
AB  - Depressive disorders are highly heterogeneous psychiatric disorders involving
      deficits to cognitive, psychomotor, and emotional processing. Considerable
      evidence links disruption to the hypothalamic-pituitary-adrenal (HPA) axis to the
      etiology of depression, with specific deficits reported in glucocorticoid
      receptor (GR)-mediated negative feedback. Given the role of GR-mediated negative
      feedback in mediating response to stress, and the clear link between stress and
      depression, it is plausible that polymorphisms in the GR gene (NR3C1) act to
      increase susceptibility. Maternal behavior in rats epigenetically alters a NGF1-A
      transcription factor binding-site in the promoter region of the GR gene,
      providing a mechanism by which environmental cues can regulate GR expression and
      thus response to stress. The analogous region of the human GR gene (NR3C1) has
      not been studied, but it is possible that polymorphisms in this region may alter
      the binding of transcription factors known to regulate GR expression. In this
      study, we have performed bioinformatic analyses on the promoter region of NR3C1
      to identify conserved promoter sequences and predicted transcription factor
      binding sites. These regions were screened with denaturing high-performance
      liquid chromatography (DHPLC) and direct re-sequencing, and several novel
      polymorphic variants were identified. We genotyped nine polymorphisms across
      NR3C1 in a large sample of Hungarian nuclear families ascertained through
      affected probands with a diagnosis of childhood-onset mood disorders (COMD).
      Single-marker analysis provided little evidence for an association of this gene
      with COMD, but multi-marker analysis across a region of high linkage
      disequilibrium revealed modest evidence for the biased transmission of several
      haplotypes.

PMID- 19089808
TI  - Association of the dystrobrevin binding protein 1 gene (DTNBP1) in a bipolar case
      control study (BACCS).
AB  - Recent studies suggest a degree of overlap in genetic susceptibility across the
      traditional categories of schizophrenia and bipolar disorder. There is some
      evidence for an association of the dystrobrevin binding protein 1 gene (DTNBP1)
      with schizophrenia, and, thus, this gene has also become a focus of further
      investigation in bipolar disorder (BD). The aim of our study is to explore the
      association of DTNBP1 with BD and with a sub phenotype, presence/absence of
      psychotic symptoms, in a sample of 515 patients with BD (ICD10/DSMIV) and 1,316
      ethnically matched control subjects recruited from the UK. Seven DTNBP1 SNPs:
      rs2743852 (SNP C), rs760761 (P1320), rs1011313 (P1325), rs3213207 (P1635),
      rs2619539 (P1655), rs16876571 and rs17470454 were investigated using the SNPlex
      genotyping system and 1 SNP (rs2619522) genotypes were imputed. Association
      analyses were conducted in a sample of 452 cases and 956 controls. We found
      significant differences in genotypic and allelic frequencies of rs3213207 and
      rs760761 of DTNBP1 between bipolar patients and controls. We also showed a global
      haplotypic association and an association of a particular haplotype with BD. Our
      results are consistent with previous studies in term of a general association
      between DTNBP1 and bipolar disorder and provide additional evidence that a
      portion of the genotypic overlap between schizophrenia and bipolar affective
      disorder is attributable to this gene.

PMID- 19089809
TI  - Antigen-loaded ER microsomes from APC induce potent immune responses against
      viral infection.
AB  - Although matured DC are capable of inducing effective primary and secondary
      immune responses in vivo, it is difficult to control the maturation and antigen
      loading in vitro. In this study, we show that ER-enriched microsomal membranes
      (microsomes) isolated from DC contain more peptide-receptive MHC I and II
      molecules than, and a similar level of costimulatory molecules to, their parental
      DC. After loading with defined antigenic peptides, the microsomes deliver
      antigenic peptide-MHC complexes (pMHC) to both CD4 and CD8 T cells effectively in
      vivo. The peptide-loaded microsomes accumulate in peripheral lymphoid organs and
      induce stronger immune responses than peptide-pulsed DC. The microsomal vaccines
      protect against acute viral infection. Our data demonstrate that peptide-MHC
      complexes armed microsomes from DC can be an important alternative to DC-based
      vaccines for protection from viral infection.

PMID- 19089810
TI  - IFN-alpha-mediated increase in cytolytic activity of maturing NK cell upon
      exposure to HSV-infected myelomonocytes.
AB  - Impaired control of chronic pathogen replication may be associated to alterations
      of NK-cell function. Whether mechanisms underlying this dysfunction involve
      perturbations of differentiating NK cells is still unknown. We studied an "in
      vitro" model of differentiation from CD34(+)Lin(-) precursors growing only
      myelomonocytes and maturing NK cells and where myelomonocytes could be suitably
      infected with HSV, HIV, or vaccinia. Cultures were evaluated by cytofluorometry
      and cytotoxicity assays for perturbations in differentiating NK cells. Increased
      expression of natural cytotoxicity receptors on maturing NK cells with increased
      cytolytic activity was observed with HSV-1 infection, and with vaccinia while no
      modulation of NK-cell phenotype nor cytotoxic activity were evident with an ssRNA
      lentivirus (HIV-1). In the presence of constant IL-12 and IL-15 concentrations,
      the observed effect did not require cell contact, involved IFN-alpha and was not
      reproduced by the addition of TLR9 agonist, nor blocked by TLR9 antagonists.
      Virus replication at sites of NK-cell precursor development may have different
      outcomes depending on the interaction between invading viruses and maturing NK
      cells. Thus, NK-cell precursors may be involved in the immune response to dsDNA
      viruses and possibly contribute to efficient control of virus infection.

PMID- 19089812
TI  - High frequency and proliferation of CD4+ FOXP3+ Treg in HIV-1-infected patients
      with low CD4 counts.
AB  - The frequency of Treg is reported to be higher in patients with chronic HIV type
      1 (HIV-1) infection and CD45RA(+) Treg exist in normal adults. In this study, we
      found a lower absolute number (15 cells/microL) but a higher proportion (16.2%)
      of FOXP3(+) cells (Treg) in the CD4(+) population in treatment-naive HIV-1
      patients with low CD4 (<200 cells/microL) counts than in those with high CD4
      counts (34 cells/microL and 9.3%) or healthy adults (48 cells/microL and 7.5%).
      In HIV-1 patients, CD45RA(+)CCR7(+), CD45RA(-)CCR7(+), and CD45RA(-)CCR7(-)
      subsets were identified in the Treg population, and the proportion of CD45RA(
      )CCR7(-) Treg was higher (57.9%) in patients with low CD4 than high CD4 counts
      (38.3%). Treg were in a high proliferation state especially in patients with low
      CD4 counts. HIV viral load correlated positively with the Treg proliferation rate
      and the proportion of CD45RA(-)CCR7(-) Treg. Furthermore, the proliferation of
      Treg correlated positively with the CD45RA(-)CCR7(-) Treg proportion but
      negatively with Treg numbers. Successful antiretroviral therapy resulted in a
      limited increase in Treg numbers, but their frequency was reduced in 1-2 months
      due to a rapid rebound of FOXP3(-) CD4(+)cells. Our results suggest that HIV
      activating Treg may be a reason for the high frequencies of Treg and CD45RA(
      )CCR7(-) Treg in the peripheral blood of late-stage HIV-1-infected patients.

PMID- 19089811
TI  - Safety and efficacy of neonatal vaccination.
AB  - Newborns have an immature immune system that renders them at high risk for
      infection while simultaneously reducing responses to most vaccines, thereby
      posing challenges in protecting this vulnerable population. Nevertheless, certain
      vaccines, such as BCG and Hepatitis B vaccine, do demonstrate safety and some
      efficacy at birth, providing proof of principal that certain antigen-adjuvant
      combinations are able to elicit protective neonatal responses. Moreover, birth is
      a major point of healthcare contact globally meaning that effective neonatal
      vaccines achieve high population penetration. Given the potentially significant
      benefit of vaccinating at birth, availability of a broader range of more
      effective neonatal vaccines is an unmet medical need and a public health
      priority. This review focuses on safety and efficacy of neonatal vaccination in
      humans as well as recent research employing novel approaches to enhance the
      efficacy of neonatal vaccination.

PMID- 19089813
TI  - Transplantation of embryonic spleen tissue reveals a role for adult non-lymphoid
      cells in initiating lymphoid tissue organization.
AB  - In this report we describe a transplantation system where embryonic spleens are
      grafted into adult hosts. This model can be used to analyze the cellular and
      molecular requirements for the development and organization of splenic
      microenvironments. Whole embryonic day 15 (ED15) spleens, grafted under the
      kidney capsule of adult mice, were colonized by host-derived lymphocytes and DC
      and developed normal splenic architecture. Grafts were also able to form germinal
      centers in response to T-dependent antigen. Using this system we demonstrated
      that adult host-derived lymphotoxin (LT) alpha was sufficient for the development
      of ED15 LT alpha(-/-) grafts. Grafting of ED15 LT alpha(-/-) spleens into RAG(-/
      ) hosts followed by transfer of LT alpha(-/-) splenocytes revealed no requirement
      for lymphocyte-derived LT alpha in the induction of CCL21 or the development of T
      zone stroma. These data suggest that interactions between adult lymphoid-tissue
      inducer-like cells and embryonic stromal cells initiated T-zone development.
      Furthermore, adult lymphoid tissue inducer-like cells were shown to develop from
      bone marrow-derived progenitors. The model described here demonstrates a method
      of transferring whole splenic microenvironments and dissecting the stromal and
      hematopoietic signals involved in spleen development and organization.

PMID- 19089814
TI  - Early recruitment of natural CD4+ Foxp3+ Treg cells by infective larvae
      determines the outcome of filarial infection.
AB  - Human helminth infections are synonymous with impaired immune responsiveness
      indicating suppression of host immunity. Using a permissive murine model of
      filariasis, Litomosoides sigmodontis infection of inbred mice, we demonstrate
      rapid recruitment and increased in vivo proliferation of CD4(+)Foxp3(+) Treg
      cells upon exposure to infective L3 larvae. Within 7 days post-infection this
      resulted in an increased percentage of CD4(+)T cells at the infection site
      expressing Foxp3. Antibody-mediated depletion of CD25(+) cells prior to infection
      to remove pre-existing 'natural' CD4(+)CD25(+)Foxp3(+) Treg cells, while not
      affecting initial larval establishment, significantly reduced the number of adult
      parasites recovered 60 days post-infection. Anti-CD25 pre-treatment also impaired
      the fecundity of the surviving female parasites, which had reduced numbers of
      healthy eggs and microfilaria within their uteri, translating to a reduced level
      of blood microfilaraemia. Enhanced parasite killing was associated with augmented
      in vitro production of antigen-specific IL-4, IL-5, IL-13 and IL-10. Thus, upon
      infection filarial larvae rapidly provoke a CD4(+)Foxp3(+) Treg-cell response,
      biasing the initial CD4(+) T-cell response towards a regulatory phenotype. These
      CD4(+)Foxp3(+) Treg cells are predominantly recruited from the 'natural'
      regulatory pool and act to inhibit protective immunity over the full course of
      infection.

PMID- 19089815
TI  - Lipid-mediated presentation of MHC class II molecules guides thymocytes to the
      CD4 lineage.
AB  - Previous studies on the MHC class-specific differentiation of CD4(+)CD8(+)
      thymocytes into CD4(+) and CD8(+) T cells have focused on the role of coreceptor
      molecules. However, CD4 and CD8 T cells develop according to their MHC class
      specificities even in these mice lacking coreceptors. This study investigated the
      possibility that lineage is determined not only by coreceptors, but is also
      guided by the way how MHC molecules are presented. MHC class II molecules possess
      a highly conserved Cys in their transmembrane domain, which is palmitoylated and
      thereby associates with lipid rafts, whereas neither palmitoylation nor raft
      association was observed with MHC class I molecules. The generation of CD4 T
      cells was impaired and that of CD8 T cells was augmented when the rafts on the
      thymic epithelial cells were disrupted. This was due to the conversion of MHC
      class II-specific thymocytes from the CD4 lineage to CD8. The ability of I-A(d)
      molecule to associate with rafts was lost when its transmembrane Cys was
      replaced. The development of DO11.10 thymocytes recognizing this mutant I-A(dm)
      was converted from CD4 to CD8. These results suggest that the CD4 lineage
      commitment is directed by the raft-associated presentation of MHC class II
      molecules.

PMID- 19089816
TI  - Tetraspanins CD37 and CD151 differentially regulate Ag presentation and T-cell co
      stimulation by DC.
AB  - A major question in immunology is how DC can display limited amounts of
      individual peptide-MHC complexes and still induce cross-linking of T-cell
      receptors to initiate cellular responses. One suggested mechanism is that MHC
      exists at the cell surface in high avidity multimers, and tetraspanin proteins,
      known to laterally associate with both MHC classes I and II, promote MHC
      multimerisation. To validate this theory, we tested the ability of DC deficient
      in either one of two typical tetraspanin molecules: CD37 or CD151 to present
      peptide to Ag-specific T cells. Surprisingly, although they exhibited no
      developmental or maturation defects, DC lacking either CD37 or CD151 expression
      were hyper-stimulatory to T cells. We demonstrate that CD37 and CD151 control DC
      mediated T-cell activation by two different mechanisms: CD151 regulates co
      stimulation whereas CD37 regulates peptide/MHC presentation. The implications of
      these results on the model suggesting that tetraspanins promote MHC
      multimerisation are discussed.

PMID- 19089817
TI  - Tumor progression inhibits the induction of multifunctionality in adoptively
      transferred tumor-specific CD8+ T cells.
AB  - It is becoming increasingly evident that the multifunctionality of effector cells
      at the single-cell level is an important factor to predict the quality of T-cell
      response in immunological protection. The significance of the multifunctionality
      of T cells in anti-tumor immunity, however, remains unclear. Here, we assessed
      the IFN-gamma and TNF-alpha production and CD107a mobilization in adoptively
      transferred tumor-antigen-specific CD8(+) T cells at the single-cell level. Tumor
      growth of the murine fibrosarcoma CMS5 was found to limit the induction of
      multifunctionality in the transferred cells. These cells exhibited insufficient
      acquisition of the CD25(high)GITR(high)CD62L(low) phenotype and reduced
      infiltration in tumor. Depletion of Treg facilitated the induction of high
      multifunctionality of the transferred cells even in the hosts with progressing
      tumor, leading to enhanced tumor regression. The multifunctionality of the
      transferred cells correlated with in vivo CTL activity, and T cells with high
      multifunctionality harvested from hosts with successful therapy induced tumor
      regression when re-transferred into the tumor-bearing hosts. These data suggest
      that the appearance of multifunctional CD8(+) effector T cells in vivo is a
      critical determinant of the success of anti-tumor immunotherapy and Treg play an
      important role in the mechanism inhibiting the induction of multifunctionality in
      effector cells.

PMID- 19089818
TI  - The biochemistry of drug metabolism--an introduction: part 6. Inter-individual
      factors affecting drug metabolism.
AB  - This review is part of a series of review articles on the metabolism of drugs and
      other xenobiotics published in Chemistry & Biodiversity. After a thorough
      discussion of metabolic reactions and their enzymes, this article focuses on
      genetically determined differences in drug and xenobiotic metabolism. After a
      short introduction on the causes for genetic differences, the first focus is on
      species differences in drug and xenobiotic metabolism. A major chapter is then
      dedicated to clinically relevant genetic polymorphisms in human drug metabolism
      and resultant ethnic differences. The last two chapters deal with sex-dependent
      differences in drug metabolism and personalized pharmacotherapy related to inter
      individual differences in drug metabolism.

PMID- 19089819
TI  - Chemical constituents of the plants of the genus Calophyllum.

PMID- 19089820
TI  - Application of molecular connectivity and electro-topological indices in
      quantitative structure-activity analysis of pyrazole derivatives as inhibitors of
      factor Xa and thrombin.
AB  - Factor Xa and thrombin, two critical pro-coagulant enzymes of the clotting
      cascade, are the primary target of current anticoagulation research that aims to
      develop potent, orally bioavailable, synthetic small-molecule inhibitors. To
      determine structural features that might play important roles in factor Xa and
      thrombin recognition and oral bioavailability, quantitative structure-activity
      and structure-property analyses were performed on the factor Xa and thrombin
      inhibition data and Caco-2 cell-permeability data of 3-substituted pyrazole-5
      carboxamides reported by Pinto et al. (J. Med. Chem. 2001, 44, 566). The factor
      Xa and thrombin inhibition potencies, and Caco-2 cell permeability of the 3
      substituted pyrazole-5-carboxamides could be quantitatively described through
      molecular connectivity and atom level E-state indices. Different quantitative
      structure-activity and structure-property models were derived for each of the
      three biological properties. The models are statistically relevant with
      correlation coefficients of at least 0.9, and contain only two or three molecular
      descriptor variables. The study demonstrates the use of molecular connectivity
      and E-state indices in understanding factor Xa and thrombin inhibition. In
      addition, the models may be useful for predictive purposes in generating
      molecules with better potency, specificity, and oral bioavailability.

PMID- 19089821
TI  - Controlled release of volatile secondary and tertiary alcohols by neighboring
      group participation: stepwise cyclization and re-opening of 2,2'
      bis(carbamoyl)dibenzoates at neutral pH.
AB  - Bioactive, volatile, secondary and tertiary fragrance alcohols are efficiently
      released by intramolecular neighboring-group-assisted hydrolysis of 2,2'
      bis(carbamoyl)dibenzoates at neutral pH. The stepwise cyclization of 2,2'
      [(methylimino)bis(propane-3,1-diylcarbamoyl)]dibenzoates is followed by the re
      opening of the intermediately formed diphthalimide and proceeds in an overall
      four-step consecutive reaction sequence. Kinetic rate constants for all four
      reaction steps could be determined pairwise by reversed-phase HPLC. At neutral
      pH, secondary alcohols were released by one order of magnitude faster than the
      tertiary alcohols, and the rate constants for the re-opening of the
      diphthalimides were found to be in the same order of magnitude as the release of
      the tertiary alcohols. Dynamic headspace analysis on a dry cotton surface finally
      confirmed the efficient release of tertiary alcohols under mild reaction
      conditions generally encountered for applications in functional perfumery.

PMID- 19089822
TI  - Characterization of the posttranscriptional modifications in Legionella
      pneumophila small-subunit ribosomal RNA.
AB  - It is generally accepted that posttranscriptional modifications in RNA play a
      role in the fine-tuning of RNA function and the maintenance of RNA structure.
      This article describes the characterization of the posttranscriptional
      modifications in Legionella pneumophila 16S rRNA by mass spectrometry and reverse
      transcriptase assays. Eight modified nucleotides were identified and mapped in
      the 16S rRNA sequence. Situation of these data in relation to general 16S rRNA
      modification patterns shows that L. pneumophila is relatively less modified, and
      that the majority of the L. pneumophila 16S rRNA modifications are conserved
      among the bacteria characterized so far (Escherichia coli, Clostridium
      acetobutylicum, Thermus thermophilus, and Thermotoga maritima).

PMID- 19089823
TI  - Intraspecific variation of the cephalic labial gland secretions in Bombus
      terrestris (L.) (Hymenoptera: Apidae).
AB  - Variations of secretions of the cephalic part of the labial glands from four
      different subspecies of Bombus terrestris, B. t. terrestris, B. t. lusitanicus,
      B. t. sassaricus, and B. t. dalmatinus, were investigated. 95 compounds were
      detected in the whole data set: 54 in B. t. terrestris, 54 in B. t. lusitanicus,
      48 in B. t. sassaricus, and 44 in B. t. dalmatinus. The (E)-2,3-dihydrofarnesol
      is the main compound in B. t. dalmatinus and B. t. sassaricus, while it is
      dihydrofarnesyl dodecanoate in B. t. terrestris and B. t. lusitanicus. A
      principal component analysis produced a pattern showing three well distinct
      groups corresponding to dalmatinus, sassaricus, and terrestris + lusitanicus.

PMID- 19089824
TI  - Host and non-host plant response to bacterial wilt in potato: role of the
      lipopolysaccharide isolated from Ralstonia solanacearum and molecular analysis of
      plant-pathogen interaction.
AB  - Ralstonia solanacearum is one of the most devastating phytopathogenic bacteria,
      in particular its race 3. This microorganism is the causal agent of destructive
      diseases of different crops including tomato and potato. An important aspect of
      the interaction between this pathogen, and the host and non-host plants was its
      biochemical and molecular basis. Thus, the lipopolysaccharides (LPS) were
      extracted from the R. solanacearum cell wall, purified, and the O-specific
      polysaccharide (OPS) was isolated and chemically characterized by compositional
      analyses and NMR spectroscopy. The OPS was constituted of two linear polymers of
      an approximate ratio of 3 : 1, both of which were built up from three rhamnose
      and one N-acetylglucosamine residues and differed only in the substitution of one
      rhamnose residue. The LPS inhibited the hypersensitivity reaction (HR) in non
      host tobacco plants and induced localized resistance in host potato plants, both
      of which were pre-treated with the LPS before being inoculated with the pathogen.
      A cDNA-AFLP approach was used to study transcriptome variation during the
      resistant and susceptible interactions. This revealed the presence of metabolites
      specifically expressed in the S. commersonii-resistant genotypes, which could be
      involved in the plant-pathogen incompatible reaction. Furthermore, a specific EST
      collection of the Ralstonia-potato interaction has been built up.

PMID- 19089825
TI  - Two new antioxidant phenylpropanoids from Lindelofia stylosa.
AB  - Two new phenylpropanoids were isolated from Lindelofia stylosa (Kar. and Kir.)
      and characterized as 4-hydroxy-N-{4-[(E)-3-(4-hydroxy-3-methoxyphenyl)prop-2
      enamido]butyl}benzamide (1) and 2-[3-hydroxy-4-(4-hydroxyphenoxy)phenyl]-1
      (methoxycarbonyl)ethyl (E)-3-(3,4-dihydroxyphenyl)prop-2-enoate (2). Four known
      compounds, i.e. two phenylpropanoids, p-coumaric acid (=(E)-3-(4
      hydroxyphenyl)prop-2-enoic acid; 3) and ferulic acid (=(E)-3-(4-hydroxy-3
      methoxyphenyl)prop-2-enoic acid; 4), and two naphthalene glycosides, 8-O-beta-D
      glucopyranosyltorachrysone (5) and 8-O-beta-D-glucopyranosyl-6
      demethoxytorachrysone (6), were also isolated for the first time from the plant.
      Compounds 1-6 were subjected to various antioxidant assays, including DPPH
      radical- and superoxide anion-scavenging, and Fe(2+)-chelation assays. Compound 2
      was found to be most active in all assays with potency nearly similar to that of
      propyl gallate. Besides 2, compounds 1 and 5 were also found to be active in DPPH
      radical-scavenging standard assay.

PMID- 19089826
TI  - Microcalorimetric investigation on effects of La(III) on metabolic activity of
      mitochondria isolated from hybrid rice.
AB  - Rare earth elements (REEs) have beneficial influence on plant growth and are
      widely used in agriculture practice, but little is known about the behavior of
      the REEs in mitochondria of plant cell. Thermogenic metabolic curves were
      determined by the ampoule method at 303 K using a TAM air isothermal
      microcalorimeter in mitochondria isolated from hybrid rice Liangyoupeijiu (Oryza
      sativa L.), and the effect of La(III) on its mitochondrial metabolism was
      investigated. From the obtained heat flux curves, the crucial parameters
      including as activity recovery rate constant (k) and maximum heat power (P(max))
      were determined. Application of La(3+) in concentrations ranging from 0 to 120
      microg/ml significantly increased k and P(max) values with the high point
      reaching 346 and 222% of the control, respectively. Concentrations from 140-150
      microg/ml had the opposite effect. These results were consistent with previous
      reports on the effects of REEs on plant growth. It was concluded that the La
      induced change of mitochondrial metabolic activity is a possible mechanism by
      which La(III) ions influences hybrid rice growth.

PMID- 19089827
TI  - Antimycobacterial butanolides from the root of Lindera akoensis.
AB  - Three racemic butanolides, majorenolide (1), majorynolide (2), and majoranolide
      (3), with 18 known compounds, including ten butanolides, i.e., litsenolide A(2)
      (4), litsenolide B(2) (5), litsenolide C(1) (6), litsenolide C(2) (7),
      hamabiwalactone A (8), hamabiwalactone B (9), litseakolide A (10), litseakolide B
      (11), isoobtusilactone (12), and obtusilactone (13); one lignan, i.e., (+/-)
      syringaresinol (14), two flavans, i.e., (+)-catechin (15), and (-)-epicatechin
      (16), one coumarin, i.e., scopoletin (17), and four steroids, i.e., a mixture of
      beta-sitosterol (18) and stigmasterol (19), and a mixture of beta-sitosteryl-3-O
      beta-D-glucoside (20) and stigmasteryl-3-O-beta-D-glucoside (21) were isolated
      from the root of Lindera akoensis. The structures of the isolates were elucidated
      by in-depth spectroscopic analysis. Compounds 1-3 were previously assigned a
      delta-lactone structure, which was then revised to a gamma-lactone structure,
      based on 1D-NMR data. The cigar-HMBC technique was used to confirm the accuracy
      of the gamma-lactone structure, and the zero [alpha] (20)_D value of compounds 1
      3 suggested that they were considerably racemized. Nine butanolides 1-3, 4-8, and
      10 showed antimycobacterial activities against M. tuberculosis H(37)Rv, with MIC
      values of 15-50 microg/ml.

PMID- 19089828
TI  - Immunosuppressive activity of the ethanol extract of Sedum sarmentosum and its
      fractions on specific antibody and cellular responses to ovalbumin in mice.
AB  - The immunosuppressive activity of the ethanol extract of Sedum sarmentosum (EESS)
      and its fractions was studied with respect to specific antibody and cellular
      response to ovalbumin (OVA) in mice. ICR Mice were immunized subcutaneously with
      OVA on days 0 and 14. Beginning on the day of immunization, the mice were
      administered intraperitoneally (ip) with EESS and it fractions at a single dose
      of 0.25, 0.5, and 1.0 mg, and cyclosporin A at a single dose of 0.1 mg at
      intervals of 7 days. On day 28, splenocyte proliferation and specific antibody
      level in serum were measured. EESS significantly suppressed concanavalin A (Con
      A)-, lipopolysaccharide (LPS)-, and OVA-induced splenocyte proliferation in the
      immunized mice in a dose-dependent manner. The OVA-specific serum IgG, IgG1, and
      IgG2b levels in the immunized mice were also markedly reduced by EESS. Among four
      fractions of EESS, the BuOH fraction consisting mainly of flavonoid glycosides
      showed the highest suppressive activity. The results suggest that EESS could
      suppress the cellular and humoral immune response in mice, and deserve further
      research to be developed as immunosuppressant.

PMID- 19089829
TI  - Polyprenylated xanthones from Garcinia lancilimba showing apoptotic effects
      against HeLa-C3 cells.
AB  - Three new prenylated xanthones, 1-3, along with ten known compounds, were
      isolated from the stem bark of Garcinia lancilimba. Their structures were
      elucidated by extensive spectroscopic analysis, including 1D- and 2D-NMR spectra,
      as well as HR-MS experiments. Some of these compounds showed apoptotic effects or
      growth-inhibition effects against HeLa cells expressing a caspase sensor protein.

PMID- 19089830
TI  - Effects of compounds isolated from the fruits of Rumex japonicus on the protein
      glycation.
AB  - An anthraquinone, emodin (1), and five flavonoids, kaempferol-3-O-beta-D
      glucoside (2), quercetin (3), quercitrin (4), isoquercitrin (5), and (+)-catechin
      (6), were isolated from an AcOEt-soluble extract of the fruits of Rumex
      japonicus. Their structures were determined by spectroscopic data interpretation.
      All the isolates were evaluated for their potential to inhibit AGEs (advanced
      glycation end products) formation and AGEs cross-linking, and to break already
      formed AGEs cross-links.

PMID- 19089831
TI  - Larvicidal and nematicidal activities of the leaf essential oil of Croton
      regelianus.
AB  - The chemical composition of the leaf essential oil of Croton regelianus collected
      from wild plants growing in two different sites at Ceara State (Brazil) was
      analyzed by GC/MS and GC-FID. Twenty monoterpenoids, representing more than 96%
      of the chemical composition of the oils, were identified and quantified. The oils
      showed similar chemical composition but considerable variation in the levels of
      each constituent. Ascaridole (33.9-17.0%), p-cymene (22.3-21.6%), and camphor
      (13.0-3.1%) were the predominant constituents. The monoterpene ascaridole was
      isolated and characterized by spectroscopic data. The essential oils and the
      isolated compounds were tested against Aedes aegypti and Artemia sp. larvae, and
      the root knot nematode Meloidogyne incognita. The bioassay results show that the
      essential oil of C. regelianus and ascaridole were moderately active against the
      M. incognita, but strongly effective against both A. aegypti and Artemia sp.
      larvae.

PMID- 19089832
TI  - Synthesis of polycyclic aromatic hydrocarbons and acetylene polymers in ice: a
      prebiotic scenario.
AB  - The recent evidences of presence of subsurface oceans of liquid water and ice on
      Saturn's moons, and the possible presence and astrobiological importance of
      polycyclic aromatic hydrocarbons (PAHs) in these environments, provide strong
      motivation for the exploration of the prebiotic chemistry in ice and to test if
      PAHs could be experimentally synthesized in ice surfaces under atmospheres
      containing methane as carbon source. In this work, we present a new design for
      prebiotic-chemistry experiments in ice matrix. Using this design, a mixture of
      products including PAHs, polar aromatic compounds, and hydrophilic acetylene
      based polymers was obtained. We propose that acetylene generation in a
      methane/nitrogen atmosphere and subsequent polymerization to PAHs and polyynes
      could be a favored pathway in the presence of water freeze-melt cycles. These
      results shed light on the processes involved in PAH synthesis in icy environments
      and on the physical factors that drive the different competing pathways in
      methane/nitrogen atmospheres.

PMID- 19089835
TI  - G72/G30 (DAOA) and juvenile-onset mood disorders.
AB  - The chromosome 13q region has been linked to bipolar disorder in a number of
      genome scans as well as focused linkage studies. Previously we identified linkage
      to the 13q32 region in a genome scan of 146 affected sibling pair families from
      Hungary with juvenile-onset mood disorders. Within this region are the
      overlapping genes G72/G30, with G72 now officially named as D-amino-acid oxidase
      activator (DAOA). This locus has been associated with panic disorder,
      schizophrenia, and bipolar disorder. In this study, we tested for association to
      11 markers in these genes and mood disorders in a sample of 646 nuclear families
      identified with a proband with onset of a mood disorder before 14.9 years of age.
      We identified evidence for association to three markers within the gene
      (rs2391191, rs3918341, rs1935062), two of which had been associated with bipolar
      disorder in previous studies. When corrected for the number of markers tested,
      the results were no longer significant, however the prior evidence for
      association of this gene in multiple studies points to this gene as a potential
      contributor to juvenile-onset mood disorders.

PMID- 19089836
TI  - Hearing loss among Ohio farm youth: a comparison to a national sample.
AB  - BACKGROUND: Hearing loss is prevalent among adults in the farming community, with
      some evidence it begins in childhood. Our objective was to compare hearing
      thresholds of Ohio farm youth to published data on national norms. METHODS:
      Baseline data were collected on youth (n = 212) in 1994-1996 with follow-up (n =
      132) in 2003-2004 including pure-tone air conduction thresholds at 0.5, 1, 2, 3,
      4, 6, and 8 kHz. RESULTS: When compared to nationally-representative data, study
      youth had a higher prevalence of hearing loss. The high-frequency range was most
      affected, particularly at 6 kHz where nearly 50% of the farm youth exhibited some
      degree of hearing loss at baseline testing. The prevalence of noise-induced
      threshold shifts, characterized by an audiometric notch, was nearly twice that of
      the national sample. CONCLUSIONS: These data suggest that hearing loss, which is
      common among adult farmers, may be problematic for farm youth as well.

PMID- 19089837
TI  - Inhibition of tumor-cell invasion with chlorotoxin-bound superparamagnetic
      nanoparticles.
AB  - Nanoparticles have been investigated as drug delivery vehicles, contrast agents,
      and multifunctional devices for patient care. Current nanoparticle-based
      therapeutic strategies for cancer treatment are mainly based on delivery of
      chemotherapeutic agents to induce apoptosis or DNA/siRNA to regulate oncogene
      expression. Here, a nanoparticle system that demonstrates an alternative approach
      to the treatment of cancers through the inhibition of cell invasion, while
      serving as a magnetic resonance and optical imaging contrast agent, is presented.
      The nanoparticle comprises an iron oxide nanoparticle core conjugated with an
      amine-functionalized poly(ethylene glycol) silane and a small peptide,
      chlorotoxin (CTX), which enables the tumor cell-specific binding of the
      nanoparticle. It is shown that the nanoparticle exhibits substantially enhanced
      cellular uptake and an invasion inhibition rate of approximately 98% compared to
      unbound CTX ( approximately 45%). Significantly, the investigation from flow
      cytometry analysis, transmission electron microscopy, and fluorescent imaging
      reveals that the CTX-enabled nanoparticles deactivated the membrane-bound matrix
      metalloproteinase 2 (MMP-2) and induced increased internalization of lipid rafts
      that contain surface-expressed MMP-2 and volume-regulating ion channels through
      receptor-mediated endocytosis, leading to enhanced prohibitory effects. Since
      upregulation and activity of MMP-2 have been observed in tumors of
      neuroectodermal origin, and in cancers of the breast, colon, skin, lung,
      prostate, ovaries, and a host of others, this nanoparticle system can be
      potentially used for non-invasive diagnosis and treatment of a variety of cancer
      types.

PMID- 19089838
TI  - Single chain epidermal growth factor receptor antibody conjugated nanoparticles
      for in vivo tumor targeting and imaging.
AB  - Epidermal growth factor receptor (EGFR) targeted nanoparticle are developed by
      conjugating a single-chain anti-EGFR antibody (ScFvEGFR) to surface
      functionalized quantum dots (QDs) or magnetic iron oxide (IO) nanoparticles. The
      results show that ScFvEGFR can be successfully conjugated to the nanoparticles,
      resulting in compact ScFvEGFR nanoparticles that specifically bind to and are
      internalized by EGFR-expressing cancer cells, thereby producing a fluorescent
      signal or magnetic resonance imaging (MRI) contrast. In vivo tumor targeting and
      uptake of the nanoparticles in human cancer cells is demonstrated after systemic
      delivery of ScFvEGFR-QDs or ScFvEGFR-IO nanoparticles into an orthotopic
      pancreatic cancer model. Therefore, ScFvEGFR nanoparticles have potential to be
      used as a molecular-targeted in vivo tumor imaging agent. Efficient
      internalization of ScFvEGFR nanoparticles into tumor cells after systemic
      delivery suggests that the EGFR-targeted nanoparticles can also be used for the
      targeted delivery of therapeutic agents.

PMID- 19089839
TI  - Direct magnetic patterning due to the generation of ferromagnetism by selective
      ion irradiation of paramagnetic FeAl alloys.
AB  - Sub-100-nm magnetic dots embedded in a non-magnetic matrix are controllably
      generated by selective ion irradiation of paramagnetic Fe(60)Al(40) (atomic %)
      alloys, taking advantage of the disorder-induced magnetism in this material. The
      process is demonstrated by sequential focused ion beam irradiation and by in
      parallel broad-beam ion irradiation through lithographed masks. Due to the low
      fluences used, this method results in practically no alteration of the surface
      roughness. The dots exhibit a range of magnetic properties depending on the size
      and shape of the structures, with the smallest dots (<100 nm) having square
      hysteresis loops with coercivities in excess of micro(0)H(C) = 50 mT.
      Importantly, the patterning can be fully removed by annealing. The combination of
      properties induced by the direct magnetic patterning is appealing for a wide
      range of applications, such as patterned media, magnetic separators, or sensors.

PMID- 19089840
TI  - Strain-driven self-assembled network of antidots in complex oxide thin films.
AB  - Structural strain due to lattice mismatch is used to promote the formation of a
      self-assembled network of antidots in highly epitaxial La(2/3)Sr(1/3)MnO(3) thin
      films grown on (001) oriented SrTiO(3) substrates by radiofrequency magnetron
      sputtering. Size, depth, and separation between antidots can be controlled by
      changing deposition parameters and the miscut angle of the substrate. This
      morphology exhibits a remarkable magnetic anisotropy and offers unique
      opportunities for versatile nanostencils for the preparation of nano-object
      networks that can be of major relevance for the fabrication of oxide-based
      magnetic and magnetoelectronic devices.

PMID- 19089841
TI  - Cancer-cell-phenotype-dependent differential intracellular trafficking of
      unconjugated quantum dots.
AB  - A diverse array of nanoparticles, including quantum dots (QDs), metals, polymers,
      liposomes, and dendrimers, are being investigated as therapeutics and imaging
      agents in cancer diseases. However, the role of the cancer-cell phenotype on the
      uptake and intracellular fate of nanoparticles in cancer cells remains poorly
      understood. Reported here is that differences in cancer-cell phenotypes can lead
      to significant differences in intracellular sorting, trafficking, and
      localization of nanoparticles. Unconjugated anionic QDs demonstrate dramatically
      different intracellular profiles in three closely related human-prostate-cancer
      cells used in the investigation: PC3, PC3-flu, and PC3-PSMA. QDs demonstrate
      punctated intracellular localization throughout the cytoplasm in PC3 cells. In
      contrast, the nanoparticles localize mainly at a single juxtanuclear location
      ("dot-of-dots") inside the perinuclear recycling compartment in PC3-PSMA cells,
      where they co-localize with transferrin and the prostate-specific membrane
      antigen. The results indicate that nanoparticle sorting and transport is
      influenced by changes in cancer-cell phenotype and can have significant
      implications in the design and engineering of nanoscale drug delivery and imaging
      systems for advanced tumors.

PMID- 19089842
TI  - Fabrication of MnxFe1-xO colloidal solid solution as a dual magnetic-resonance
      contrast agent.

PMID- 19089843
TI  - Effects of litter-overlapping on emotionality, stress response, and reproductive
      functions in male and female rats.
AB  - In rats, mating at postpartum estrus and delayed dispersal of the young would
      result in the overlapping of two different-age litters. As a consequence, newborn
      pups' early experience will include not only that acquired during the interaction
      with the mother and age-matched littermates, but also with older siblings. As
      early-life experience modulates rodents' brain function, behavior and
      reproduction, we aimed to assess how changes in the early environment provoked by
      the overlapping of litters would affect emotionality, stress response and
      reproductive functions of male and female pups during adulthood. Results showed
      that both male and female overlapped reared pups exhibited a reduced behavioral
      inhibition in the open field test during adulthood. In addition, overlapped
      reared adult females, but not males, showed a blunted corticosterone response to
      an acute stressor during diestrus and a reduction in sexual behavior. In summary,
      natural changes in early experience provoked by the overlapping of litters, long
      term modulate affective and reproductive behaviors, and the endocrine stress
      response in a sex dimorphic manner.

PMID- 19089844
TI  - PEL: an unbiased method for estimating age-dependent genetic disease risk from
      pedigree data unselected for family history.
AB  - Providing valid risk estimates of a genetic disease with variable age of onset is
      a major challenge for prevention strategies. When data are obtained from
      pedigrees ascertained through affected individuals, an adjustment for
      ascertainment bias is necessary. This article focuses on ascertainment through at
      least one affected and presents an estimation method based on maximum likelihood,
      called the Proband's phenotype exclusion likelihood or PEL for estimating age
      dependent penetrance using disease status and genotypic information of family
      members in pedigrees unselected for family history. We studied the properties of
      the PEL and compared with another method, the prospective likelihood, in terms of
      bias and efficiency in risk estimate. For that purpose, family samples were
      simulated under various disease risk models and under various ascertainment
      patterns. We showed that, whatever the genetic model and the ascertainment
      scheme, the PEL provided unbiased estimates, whereas the prospective likelihood
      exhibited some bias in a number of situations. As an illustration, we estimated
      the disease risk for transthyretin amyloid neuropathy from a French sample and a
      Portuguese sample and for BRCA1/2 associated breast cancer from a sample
      ascertained on early-onset breast cancer cases.

PMID- 19089845
TI  - Trends and changes in the clinical use of lamotrigine.
AB  - PURPOSE: To investigate long-term trends and changes in the pattern of use of
      lamotrigine (LTG). METHODS: Retrospective survey of a large, routine therapeutic
      drug monitoring database. RESULTS: Twelve thousand one hundred and seven samples
      from 4123 subjects were analysed from October 1999 to May 2007. Within this
      period, the mean daily dose rose from 183 to 253 mg, whereas the median dose
      remained unchanged at 200 mg. Females became the majority of LTG users, and they
      had a higher proportion of psychiatric diagnoses than male patients. The mean
      patient age increased from 34 to 41 years. The proportion of samples from
      psychiatric patients became larger than that of neurologic patients. A total of
      130 different diagnoses were stated, most of them psychiatric off-label. The mean
      serum concentration was 3.8 mg/L and it remained quite stable during the whole
      observation period. Neurologic patients had a higher mean serum concentration
      than psychiatric patients. 30% of the neurologic and 41% of the psychiatric
      patients had serum concentrations below the reference range. Sixty-eight per cent
      of the patients used additional drugs. Females used a higher number of additional
      medications than males. The 10 most frequent co-medications consisted of seven
      psychotropic drugs, two anticonvulsants, and thyroxine. CONCLUSIONS: Significant
      changes in the pattern of use of LTG have taken place during the observation
      period and some significant trends could be identified.

PMID- 19089846
TI  - Somatic and non-affective symptoms of old age depression: ethnic differences
      among Chinese, Indians and Malays.
AB  - BACKGROUND: Somatic and other non-affective symptomatology characterizes late
      life depression and contributes to its under-diagnosis, especially in some ethnic
      groups. OBJECTIVES: We examined variations in non-affective presentation and its
      health and functional significance across different ethnic groups of Chinese,
      Malays and Indians. METHOD: We analyzed data from the National Mental Health
      Survey for Elderly, a population-based cross-sectional study of older adults aged
      60 and above (N = 1092). RESULTS: Compared to the depressed Chinese as the
      reference group, depressed Malays were more likely to endorse symptoms of
      appetite decrease (OR = 5.19), sleep disturbances (OR = 2.93), disabling pain (OR
      = 3.12), psychomotor slowing (OR = 2.73) and anergia (OR = 3.70), while
      concurrently reporting poorer general health status and greater role limitations
      resulting from their mental and emotional problems (OR from 2.13 to 3.31). These
      differences were not influenced by anxiety, dementia or physical comorbidity.
      CONCLUSION: We revealed striking differences in the somatic and non-affective
      symptomatology of geriatric depression among different Asian ethnic groups. Non
      affective symptoms in depression have large health and functional significance
      and important implications for the diagnosis and management of depression among
      elderly in primary care.

PMID- 19089847
TI  - Dementia: an anthropological perspective.

PMID- 19089848
TI  - A new approach to aid the characterisation and identification of metabolites of a
      model drug; partial isotope enrichment combined with novel formula elucidation
      software.
AB  - This work describes the identification of 'isotopically enriched' metabolites of
      4-cyanoaniline using the unique features of the software package 'Spectral
      Simplicity'. The software is capable of creating the theoretical mass spectra for
      partially isotope-enriched compounds, and subsequently performing an elemental
      composition analysis to give the elemental formula for the 'isotopically
      enriched' metabolite. A novel mass spectral correlation method, called
      'FuzzyFit', was employed. 'FuzzyFit' utilises the expected experimental
      distribution of errors in both mass accuracy and isotope pattern and enables
      discrimination between statistically probable and improbable candidate formulae.
      The software correctly determined the molecular formulae of ten previously
      described metabolites of 4-cyanoaniline confirming the technique of partial
      isotope enrichment can produce results analogous to standard methodologies. Six
      previously unknown species were also identified, based on the presence of the
      unique 'designer' isotope ratio. Three of the unknowns were tentatively
      identified as N-acetylglutamine, O-methyl-N acetylglucuronide and a putative
      fatty acid conjugate. The discovery of a significant number of unknown species of
      a model drug with a comprehensive history of investigation highlights the
      potential for enhancement to the analytical process by the use of 'designer'
      isotope ratio compounds. The 'FuzzyFit' methodology significantly aided the
      elucidation of candidate formulae, by provision of a vastly simplified candidate
      formula data set.

PMID- 19089849
TI  - Thymoquinone protects dopaminergic neurons against MPP+ and rotenone.
AB  - Thymoquinone is the main active constituent of Nigella sativa seeds with
      antioxidant and antiinflammatory properties. In the present study, primary
      dopaminergic cultures from mouse mesencephala were used to investigate the
      neuroprotective effects of thymoquinone against MPP(+) and rotenone toxicities.
      MPP(+) (10 microm on day 10 in vitro (i.v.) for 48 h) significantly decreased the
      number of THir by 40% compared with untreated control cultures. Rotenone at both
      short (20 nm on day 10 i.v. for 48 h) and long-term (1 nm on day 6 i.v. for 6
      consecutive days) toxicities reduced the number of THir neurons by 33% and 24%,
      respectively. Treatment of cultures with thymoquinone (0.01, 0.1, 1, 10 microm on
      day 8 i.v. for 4 days) rescued about 25% of THir neurons at concentrations of 0.1
      microm and 1 microm against MPP(+)-induced cell death. Against rotenone,
      thymoquinone afforded significant protection in both short- and long-term models.
      In short-term rotenone toxicity, thymoquinone (from days 8-12 i.v.) saved about
      65%, 74% and 79% of THir neurons at concentrations of 0.01, 0.1 and 1 microm,
      respectively, compared with cell loss induced by rotenone. In long-term rotenone
      toxicity, concomitant treatment of cultures with thymoquinone significantly
      rescued about 83-100% of THir neurons compared with rotenone-treated cultures. In
      conclusion, the current study presents for the first time the potential of
      thymoquinone to protect primary dopaminergic neurons against MPP(+) and rotenone
      relevant to Parkinson's disease.

PMID- 19089850
TI  - An integrated proteomics approach for studying the molecular pathogenesis of
      Dupuytren's disease.
AB  - Dupuytren's disease (DD) is a fibromatosis characterized by non-malignant
      transformation of palmar fascia leading to permanent contraction of one or more
      fingers. Despite the extensive knowledge of its clinical pathogenesis, the
      aetiology of this disease remains obscure. In the present paper, we report for
      the first time on the proteomic profiling of diseased versus unaffected patient
      matched palmar fasciae tissues from DD patients using two-dimensional gel
      electrophoresis coupled with mass spectrometry analysis. The herein identified
      proteins were then used to create the protein-protein interaction network
      (interactome). Such an integrated approach revealed the involvement of several
      different molecular processes related to DD progression, including extra- and
      intra-cellular signalling, oxidative stress, cytoskeletal changes, and
      alterations in cellular metabolism. In particular, autocrine regulation through
      ERBB-2 and IGF-1R receptors and the Akt signalling pathway have emerged as novel
      components of pro-survival signalling in Dupuytren's fibroblasts and thus might
      provide a basis for a new therapeutic strategy in Dupuytren's disease.

PMID- 19089851
TI  - Green peach aphid, Myzus persicae (Hemiptera: Aphididae), reproduction during
      exposure to sublethal concentrations of imidacloprid and azadirachtin.
AB  - BACKGROUND: Resurgence of insect pests following insecticide applications is
      often attributed to natural enemy disturbance, but hormesis could be an
      alternative or additional mechanism. Green peach aphid, Myzus persicae (Sulzer),
      is an important insect pest of many crops worldwide that may be exposed to
      sublethal insecticide concentrations over time. Here, the hypothesis that
      exposure to low concentrations of imidacloprid and azadirachtin can induce
      hormetic responses in M. persicae is tested in the laboratory. RESULTS: When
      insects were exposed to potato leaf discs dipped in sublethal concentrations of
      insecticide, almost all measured endpoints-adult longevity, F1 production, F1
      survival and F2 production-were affected, and a statistically significant (P <
      0.05) stimulatory response was recorded for F2 production following exposure to
      imidacloprid. No other measures for hormesis were statistically significant, but
      other trends of hormetic response were consistently observed. CONCLUSIONS: Given
      that variable distribution and degradation of insecticides in the field would
      result in a wide range of concentrations over time and space, these laboratory
      experiments suggest that exposure to sublethal concentrations of imidacloprid and
      azadirachtin could stimulate reproduction in M. persicae.

PMID- 19089852
TI  - Risk assessment of thiacloprid and its chemical decontamination on eggplant,
      Solanum melongena L.
AB  - BACKGROUND: Thiacloprid [(Z)-3-(6-chloro-3-pyridylmethyl)-1,3-thiazolidin-2
      ylidenecyanamide; Calypso] is a systemic insecticide having persistence in the
      plant system. It was chosen for the management of the eggplant shoot and fruit
      borer, Leucinodes orbonalis Guen. Management of this insect pest is difficult
      because it harbours inside the shoot and fruit portions of eggplant. The
      persistence of thiacloprid on eggplant has not been studied in India. The Food
      and Agriculture Organisation (FAO) has proposed its maximum residue limit (MRL)
      on eggplant as 0.7 mg kg(-1), and there is a need to validate this value. Since
      residues were found to be above this level, five different decontamination agents
      were tested for the decontamination of thiacloprid from eggplant. RESULTS: The
      half-life of thiacloprid was 11.1 and 11.6 days from trials in 2 years. Safety
      factors such as theoretical maximum daily intake (TMDI) and maximum permissible
      intake (MPI) were used to arrive at a risk assessment to human health from the
      analytical data obtained from the field trials. Thiacloprid at the doses tested
      (30 and 60 g AI ha(-1)) was not effective in managing eggplant fruit borer. A
      waiting period of 3 days before harvest of the fruits after insecticide
      application and a processing factor (PF) could not ensure a sufficient margin of
      safety (MOS). Subjecting the data to a processing factor of 60% could not bring
      the residues below the proposed MRL. CONCLUSION: Thiacloprid is not found to be
      an appropriate and effective agent for application to eggplant. Either the
      proposed MRL needs to be revised or good agricultural practice involving
      thiacloprid for plant protection in eggplant cultivation is required.

PMID- 19089853
TI  - Extracting metabolite ions out of a matrix background by combined mass defect,
      neutral loss and isotope filtration.
AB  - Mass defect, neutral loss and isotope filtration techniques were applied to
      electrospray ionization mass spectrometry (ESI-MS) data obtained for in vivo and
      in vitro samples of drug metabolism studies. A combination of these post
      acquisition processing techniques was shown to be more powerful than the use of
      one of these tools alone for the detection in complex matrices of metabolites of
      candidate drugs with a characteristic isotope pattern (e.g. containing bromine,
      chlorine, or a high proportion of radiolabeled drug ((12)C/(14)C)) or
      characteristic neutral losses. In combination with 'all-in-one' data acquisition
      this methodology is able to perform software-driven constant neutral loss
      scanning for an unlimited number of mass differences at any time after analysis.
      Highly selective MS chromatograms were obtained with excellent correlation with
      their corresponding radiochromatograms.

PMID- 19089854
TI  - Acute toxicity of parabens and their chlorinated by-products with Daphnia magna
      and Vibrio fischeri bioassays.
AB  - The acute toxicity of 21 parabens and their chlorinated derivatives was
      investigated by means of two toxicity bioassays: Daphnia magna immobilization
      test and the inhibition of bioluminescence of Vibrio fischeri. The median
      effective concentration (EC(50)) values of the tested parabens ranged from 2.2 to
      62 mg l(-1) in the D. magna test and from 0.0038 to 5.9 mg l(-1) in the V.
      fischeri test at 15 min after exposure. The toxicity of dichlorinated methyl- and
      n-propylparaben, the most commonly used preservatives in cosmetics, toward D.
      magna was 3.9- and 2.8-fold that of their corresponding parent compounds.
      Toxicity toward D. magna showed a linear relationship with log P, indicating that
      toxicity increases with increasing hydrophobicity. On the other hand, the
      correlations of toxicity toward V. fischeri with hydrophobicity and with the
      degree of chlorination were poor. In addition, the results of the present study
      indicated that the V. fischeri test was more sensitive than the D. magna test for
      the determination of the acute toxicity of parabens. A complete assessment of the
      ecological and toxicological risks of parabens may require the examination of
      chlorinated parabens as well as the parent pollutants, as described in the
      present study.

PMID- 19089855
TI  - Metabolic turnover rates of carbon and nitrogen stable isotopes in captive
      juvenile snakes.
AB  - Metabolic turnover rates (m) of delta(15)N and delta(13)C were assessed in
      different tissues of newly hatched captive-raised corn snakes (Elaphe guttata
      guttata) fed maintenance diets consisting of earthworms (Eisenia foetida) that
      varied substantially in delta(15)N (by 644 per thousand) and delta(13)C (by 5.0
      per thousand). Three treatments were used during this 144 day experiment that
      consisted of the same diet throughout (control), shifting from a depleted to an
      enriched stable isotope signature diet (uptake), and shifting from an enriched to
      depleted stable isotope signature diet (elimination). Values of delta(13)C in the
      liver, blood, and muscle of the control snakes reached equilibrium with and were,
      respectively, 1.73, 2.25 and 2.29 greater than in their diet, this increase is
      called an isotopic discrimination factor (Deltadelta(13)C = delta(13)C(snake) -
      delta(13)C(food)). Values of delta(15)N in snake tissues did not achieve
      equilibrium with the diets in any of the exposures and thus Delta(15)N could not
      be estimated. Values of metabolic turnover rates (m) for delta(13)C and
      delta(15)N were greater in liver than in muscle and blood, which were similar,
      and relative results remained the same if the fraction of (15)N and (13)C were
      modeled. Although caution is warranted because equilibrium values of stable
      isotopes in the snakes were not achieved, values of m were greater for delta(13)C
      than delta(15)N, resulting in shorter times to dietary equilibrium for delta(13)C
      upon a diet shift, and for both stable isotopes in all tissues, greater during an
      elimination than in an uptake shift in diet stable isotope signature. Multiple
      explanations for the observed differences between uptake and elimination shifts
      raise new questions about the relationship between animal and diet stable isotope
      concentrations. Based on this study, interpretation of feeding ecology using
      stable isotopes is highly dependent on the kind of stable isotope, tissue,
      direction of diet switch (uptake versus elimination), and the growth rate of the
      animal.

PMID- 19089856
TI  - Determination of delta(18)O in soils: measuring conditions and a potential
      application.
AB  - The stable oxygen isotope signature (delta(18)O) of soil is expected to be the
      result of a mixture of components within the soil with varying delta(18)O
      signatures. Thus, the delta(18)O of soils should provide information about the
      soil's substrate, especially about the relative contribution of organic matter
      versus minerals. As there is no standard method available for measuring soil
      delta(18)O, the method for the measurement of single components using a high
      temperature conversion elemental analyser (TC/EA) was adapted. We measured
      delta(18)O in standard materials (IAEA 601, IAEA 602, Merck cellulose) and soils
      (organic and mineral soils) in order to determine a suitable pyrolysis
      temperature for soil analysis. We consider a pyrolysis temperature suitable when
      the yield of signal intensity (intensity of mass 28 per 100 microg) is at a
      maximum and the acquired raw delta(18)O signature is constant for the standard
      materials used and when the quartz signal from the soil is still negligible.
      After testing several substances within the temperature range of 1075 to 1375
      degrees C we decided to use a pyrolysis temperature of 1325 degrees C for further
      measurements. For the Urseren Valley we have found a sequence of increasing
      delta(18)O signatures from phyllosilicates to upland soils, wetland soils and
      vegetation. Our measurements show that the delta(18)O values of upland soil
      samples differ significantly from wetland soil samples. The latter can be related
      to the changing mixing ratio of the mineral and organic constituents of the soil.
      For wetlands affected by soil erosion, we have found intermediate delta(18)O
      signatures which lie between typical signatures for upland and wetland sites and
      give evidence for the input of upland soil material through erosion.

PMID- 19089857
TI  - Including prenatal diagnoses in birth defects monitoring: Experience of the
      Metropolitan Atlanta Congenital Defects Program.
AB  - BACKGROUND: Advances in prenatal diagnosis have led to changes in the management
      of pregnancies affected with birth defects. These changes pose unique challenges
      for birth defects monitoring programs which use hospital-based sources. METHODS:
      In 1994, Metropolitan Atlanta Congenital Defects Program (MACDP) abstractors
      began to visit area perinatologists' offices to identify pregnancies diagnosed
      prenatally with fetal defects. These pregnancies were then linked with existing
      MACDP cases and the hospital deliveries abstracted. Those without a hospital
      delivery were included as having unknown outcomes. Prenatally diagnosed defects
      were classified as definite or possible based on the certainty of the prenatal
      description. For 1995-2004, we calculated minimum and maximum adjusted defect
      prevalences by adding definite prenatal defects, and definite plus possible
      prenatal defects, to the hospital-based cases. RESULTS: We identified 1009
      pregnancies with a prenatally diagnosed defect not ascertained from MACDP
      hospital sources. Including these increased the total defect prevalence from 28
      per 1000 live births to a minimum of 29.94 (6.9% increase) and maximum of 30.14
      (7.7% increase) per 1000. The minimum increase was greater than 50% for conjoined
      twins, triploidy, craniorachischisis, cystic hygroma, Klinefelter syndrome,
      anencephaly, Turner syndrome, and trisomies 13, 18 and 21 among mothers >or=35.
      CONCLUSIONS: These data reflect the variety of congenital abnormalities that can
      be detected prenatally and the importance of including prenatal diagnoses in
      birth defects monitoring data. Birth defects monitoring programs should assess
      individually the extent to which prenatal diagnosis can affect the accuracy and
      completeness of their data. Birth Defects Research (Part A), 2009. Published 2008
      Wiley-Liss, Inc.

PMID- 19089858
TI  - A review of Donnai-Barrow and facio-oculo-acoustico-renal (DB/FOAR) syndrome:
      clinical features and differential diagnosis.
AB  - Mutations in the gene LRP2 have recently been identified as the cause of Donnai
      Barrow and Facio-oculo-acoustico-renal (DB/FOAR) syndrome. More than two dozen
      cases, the first reported more than 30 years ago by Holmes, have been published.
      Summarizing available information, we highlight the cardinal features of the
      disorder found in >or=90% of published cases. These features include: agenesis of
      the corpus callosum, developmental delay, enlarged anterior fontanelle, high
      myopia, hypertelorism, proteinuria, and sensorineural hearing loss. Congenital
      diaphragmatic hernia and omphalocele are reported in only half of the patients.
      There is no evidence for genotype-phenotype correlation, though the sample size
      is too small to preclude this with certainty. Although several conditions to
      consider in the differential diagnosis are highlighted, the diagnosis of DB/FOAR
      syndrome should not be difficult to establish as its constellation of findings is
      strikingly characteristic.

PMID- 19089859
TI  - Gas-phase fragmentation study of a novel series of synthetic 2-oxo-2H
      benzopyrano[2,3-d]pyrimidine derivatives using electrospray ionization tandem
      mass spectroscopy measured with a quadrupole orthogonal time-of-flight hybrid
      instrument.
AB  - The fragmentation patterns of a series of six novel synthesized
      benzopyranopyrimidine derivatives 1-6, possessing the same 2-oxo-2H
      benzopyrano[2,3-d]pyrimidine backbone structure, were investigated by
      electrospray ionization mass spectrometry (ESI-MS) and tandem mass spectrometry
      (MS/MS) techniques using a quadrupole orthogonal time-of-flight (QqToF)-hybrid
      instrument. The series of six pure benzopyranopyrimidine compounds contained
      three constitutional isobaric isomers (compounds 4-6). A simple methodology,
      based on the use of ESI (positive ion mode) and increasing the declustering
      potential in the atmospheric pressure/vacuum interface resulting in collision
      induced dissociation (CID), was used to enhance the formation of the product
      ions. In general, the novel synthetic benzopyranopyrimidine derivatives 1-6
      afforded exact accurate masses for the protonated molecules. This led to the
      confirmation of both molecular masses and chemical structures of the studied
      compounds. The breakdown routes of the protonated molecules were rationalized by
      conducting low-energy CID-MS/MS analyses. It was shown that the MS/MS
      fragmentation routes for the protonated molecules 1 and 2 were similar, and that
      the MS/MS fragmentations of the constitutional isobaric protonated molecules 5
      and 6 were identical. It was also shown that the gas-phase CID fragmentations of
      5 and 6 were different from that of their constitutional isomer 4. Finally, the
      ESI-MS and CID-MS/MS analyses of the protonated molecules that were obtained from
      the monodeuterated benzopyranopyrimidine derivatives 1-6 confirmed the values
      obtained for the exact masses, the precise structural assignments of all product
      ions and all the pathways described in the proposed CID fragmentations.

PMID- 19089860
TI  - Derivatization of sialic acids for stabilization in matrix-assisted laser
      desorption/ionization mass spectrometry and concomitant differentiation of
      alpha(2 --> 3)- and alpha(2 --> 6)-isomers.
AB  - Sialylated carbohydrates usually decompose by loss of sialic acid when ionized by
      matrix-assisted laser desorption/ionization (MALDI) as the result of the labile
      carboxylic proton. Stabilization has previously been achieved by forming methyl
      esters with methyl iodide, a procedure that eliminates the labile proton. In this
      paper, we describe an alternative procedure for methyl ester formation that
      provides information on the sialic acid linkage directly from the MALDI spectrum.
      The sugars were desalted, dissolved in methanol, and treated with 4-(4,6
      dimethoxy-1,3,5-triazin-2-yl)-4-methylmorpholinium chloride (DMT-MM). After
      removal of the solvent, the products were transferred directly to the MALDI
      target and examined from 2,5-dihydroxybenzoic acid. Small amounts of N-glycans
      derived from biological sources benefited from an additional clean-up stage
      involving Nafion 117. alpha(2 --> 6)-Linked sialic acid produced only methyl
      esters whereas alpha(2 --> 3)-linked sialic acids were converted into their
      lactones providing a 32 Da difference in mass. Negative ion collision-induced
      decomposition (CID) mass spectra of these neutralized glycans provided
      information, in many cases, on the antenna of N-linked glycans to which the
      variously linked sialic acids were attached. The method was applied to N-linked
      glycans released from bovine fetuin and porcine thyroglobulin.

PMID- 19089861
TI  - Hybrid numerical techniques for the modelling of radiofrequency coils in MRI.
AB  - Radiofrequency (RF) coils for use in MRI can have a significant effect on both
      the signal-to-noise-ratio of MR images and the specific absorption rate inside
      the biological sample. In the past, prototypes were constructed and tested to
      investigate the performance of the RF coils and often required several iterations
      to achieve an acceptable result. However, with the advancement in computational
      electromagnetic techniques, RF coil modelling has now become the modus operandi
      of coil design because it can produce accurate numerical results, thus reducing
      the time and effort spent in designing and prototyping RF coils. Two hybrid
      methods -method of moments (MoM)/finite difference time domain (FDTD) and
      MoM/finite element method (FEM) - for RF coil modelling are presented herein. The
      paper provides a brief overview of FDTD, FEM and MoM. It discusses the
      hybridisation of these methods and how they are integrated to form versatile
      techniques. The numerical results obtained from these hybrid methods are compared
      with experimental results from prototype coils over a range of operating
      frequencies. The methods are then applied to the design of a new type of phased
      array coil - the rotary phased array. From these comparisons, it can be seen that
      the numerical methods provide a useful aid for the design and optimisation of RF
      coils for use in MRI.

PMID- 19089862
TI  - Electrospray ionization tandem mass spectrometry fragmentation of protonated
      flavone and flavonol aglycones: a re-examination.
AB  - Flavonoids are important phytochemicals which have been intensively studied in
      the last decades in view of their antioxidant activity, which is of particular
      importance in the case of flavones and flavonols, that differ in a single 3-OH
      group. Mass spectrometry has been used to elucidate the structures of many types
      of flavonoids and their metabolites. The work we present here is focused on the
      electrospray ionization tandem mass spectrometry (ESI-MS/MS) analysis of flavone
      and flavonols aglycones. Their fragmentation mechanisms in the positive ion mode
      are described and compared with previously reported mechanisms. We analyzed
      flavonoid derivatives produced by reaction of the flavonoids with chemically
      synthesized hypohalous acids (HOCl, HOBr and HOI) and peroxynitrite, reactive
      species involved in the inflammatory response. All the proposed pathways have
      been analyzed using computational chemistry methods in order to seek for possible
      variations and establish the most plausible ones. We observed that the losses of
      one and two CO molecules can be useful in terms of antioxidant activity
      prediction. Losses of one and two C(2)H(2)O groups are also informative in terms
      of structure and activity predictions. The retro-Diels-Alder fragmentations, and
      subsequent neutral losses, were reviewed and, according to our calculations, the
      most plausible structures for the product ions were established. These
      fingerprints will be of great value for differentiating flavonoids from other
      compounds in complex biological mixtures and for a thorough structural
      identification of flavonoid aglycones and their in vivo metabolites.

PMID- 19089863
TI  - Metabolism of androsta-1,4,6-triene-3,17-dione and detection by gas
      chromatography/mass spectrometry in doping control.
AB  - The urinary metabolism of the irreversible aromatase inhibitor androsta-1,4,6
      triene-3,17-dione was investigated. It is mainly excreted unchanged and as its
      17beta-hydroxy analogue. For confirmation, 17beta-hydroxyandrosta-1,4,6-trien-3
      one was synthesized and characterized by nuclear magnetic resonance (NMR) in
      addition to the parent compound. In addition, several reduced metabolites were
      detected in the post-administration urines, namely 17beta-hydroxyandrosta-1,4
      dien-3-one (boldenone), 17beta-hydroxy-5beta-androst-1-en-3-one (boldenone
      metabolite), 17beta-hydroxyandrosta-4,6-dien-3-one, and androsta-4,6-diene-3,17
      dione. The identification was performed by comparison of the metabolites with
      reference material utilizing gas chromatography/mass spectrometry (GC/MS) of the
      underivatized compounds and GC/MS and GC/tandem mass spectrometry (MS/MS) of
      their trimethylsilyl (TMS) derivatives. Alterations in the steroid profile were
      also observed, most obviously in the androsterone/testosterone ratio. Even if not
      explicitly listed, androsta-1,4,6-triene-3,17-dione is classified as a prohibited
      substance in sports by the World Anti-Doping Agency (WADA) due to its aromatase
      inhibiting properties. In 2006 three samples from human routine sports doping
      control tested positive for metabolites of androsta-1,4,6-triene-3,17-dione. The
      samples were initially found suspicious for the boldenone metabolite 17beta
      hydroxy-5beta-androst-1-en-3-one. Since metabolites of androst-4-ene-3,6,17
      trione were also present in the urine samples, it is presumed that these findings
      were due to the administration of a product like 'Novedex Xtreme', which could be
      easily obtained from the sport supplement market.

PMID- 19089864
TI  - Retracted: Genetic diversity in hepatitis C virus (HCV): A brief review.
AB  - The following article from Reviews in Medical Virology, Genetic diversity in
      hepatitis C virus (HCV) a brief review, by M Irshad, published online on December
      16 2008 in Wiley InterScience (www.interscience.wiley.com) has been retracted by
      agreement between the author, the journal Editor in Chief, P.D. Griffiths, and
      the publisher Wiley Blackwell. The retraction has been agreed due to overlap with
      the following article by P Simmonds, Genetic diversity and evolution of hepatitis
      C virus fifteen years on, published in Journal of General Virology, 2004, 85,
      3173-3178.

PMID- 19089866
TI  - Phenolic hydroxy groups incorporated for the peroxidase-catalyzed gelation of a
      carboxymethylcellulose support: cellular adhesion and proliferation.
AB  - The effect of Ph-OH group content on gelation time, mechanical properties,
      hydrophobicity, and cellular adhesiveness of hydrogels produced from
      carboxymethylcellulose derivatives is investigated. A higher Ph-OH group content
      induces faster gelation and yields more brittle and hydrophobic gels. After 4 h
      of seeding, a larger number of L929 fibroblasts adhere to the hydrogel of the CMC
      Ph that contains 15.4 Ph-OH groups per 100 repeat units of uronic acid (97%
      adhesion rate) than to the gel of CMC-Ph with only 8.4 Ph-OH groups (62% adhesion
      rate). The results demonstrate that controlling the Ph-OH group content is an
      effective and useful way to control cellular adhesion and proliferation on the
      hydrogels, as well as gelation time and mechanical properties of the gels.

PMID- 19089865
TI  - Cellulose derivatives carrying triphenylamine (TPA) moieties: synthesis and
      electro-optical properties.
AB  - A novel ethyl cellulose derivative [poly(1)] that carries triphenylamine moieties
      is synthesized with a moderate number-average molecular weight up to 78,200 in
      85% yield by the reaction of 4-(diphenylamino)benzoic acid with the residual
      hydroxy group of ethyl cellulose. Poly(1) is soluble in common organic solvents
      including toluene, CHCl3, CH2Cl2, and tetrahydrofuran while insoluble in hexane,
      diethyl ether, and methanol. The polymer emits blue-green fluorescence with
      quantum yields up to 65% in CHCl3 and displays unique solvatochromism. The cyclic
      voltammograms of poly(1) indicate that the polymer carrying TPA moieties is
      electrochemically redox active. The onset temperature of weight loss of the
      poly(1) is about 177 degrees C according to thermogravimetric analysis in air.

PMID- 19089868
TI  - Higher and higher!

PMID- 19089867
TI  - Amphiphilic multi-arm block copolymer based on hyperbranched polyester, poly(L
      lactide) and poly(ethylene glycol) as a drug delivery carrier.
AB  - A novel type of biodegradable/biocompatible amphiphilic hyperbranched copolymer
      (H40-PLA-b-MPEG) was synthesized. Its micellar properties were studied by DLS,
      fluorescence spectroscopy and TEM. The drug release profile showed that the H40
      PLA-b-MPEG micelles provide an initial burst release, followed by a sustained
      release of the entrapped hydrophobic model drug over a period of 4 to 58 h. The
      copolymer degraded hydrolytically within 6 weeks under physiological conditions.
      The MTT assay showed no obvious cytotoxicity against a human endothelial cell
      line at a concentration range of 0-400 microg x mL(-1). These results indicate
      that the H40-PLA-b-MPEG micelles have great potential as hydrophobic drug
      delivery carriers.

PMID- 19089869
TI  - Core crosslinking of biodegradable block copolymer micelles based on poly(ester
      carbonate).
AB  - A biodegradable amphiphilic block copolymer, PEG-b-P(LA-co-MAC), was used to
      prepare spherical micelles consisting of a hydrophobic P(LA-co-MAC) core and a
      hydrophilic PEG shell. To improve their stability, the micelles were crosslinked
      by radical polymerization of the double bonds in the hydrophobic blocks. The
      crosslinked micelles had similar sizes and a narrow size distribution compared to
      their uncrosslinked precursor. The improved stability of the crosslinked micelles
      was confirmed by measurements of the CMC and a thermodynamic investigation. These
      micelles can internalize into Hela cells in vitro as demonstrated by inverted
      fluorescence microscopy and CLSM. These stabilized nanoscale micelles have
      potential use in biomedical applications such as drug delivery and disease
      diagnosis.

PMID- 19089870
TI  - Functional PLGA scaffolds for chondrogenesis of bone-marrow-derived mesenchymal
      stem cells.
AB  - Two chondrogenic factors, Dex and TGF-beta1, were incorporated into PLGA
      scaffolds and their chondrogenic potential was evaluated. The Dex-loaded PLGA
      scaffold was grafted with AA and heparin, the heparin-immobilized one was then
      reacted with TGF-beta1, yielding a PLGA/Dex-TGF (PLGA/D/T) scaffold. The
      scaffolds were seeded with rabbit MSCs and cultured for 4 weeks. The results show
      that the scaffolds including chondrogenic factors strongly upregulated the
      expression of cartilage-specific genes and clearly displayed type-II collagen
      immunofluorescence. The functionalized PLGA scaffolds could provide an
      appropriate niche for chondrogenic differentiation of MSC without a constant
      medium supply of Dex and TGF-beta1.

PMID- 19089871
TI  - Polyelectrolyte coated PLGA nanoparticles: templation and release behavior.
AB  - Poly[(D,L-lactide)-co-glycolide] nanoparticles coated with polyethyleneimine on
      their surface were prepared by an emulsification-solvent evaporation method and
      subsequently surface modified by LBL assembly. The assembly of poly(acrylic acid)
      and polyethyleneimine on a planar substrate and on the PLGA nanoparticles was
      monitored by QCM-D, zeta-potential, flow cytometry and TEM. Carboxylic and amino
      groups in the multilayers were crosslinked by carbodiimide condensation, which
      was also later used to graft poly(ethylene glycol) (PEG). Rhodamine 6G, 5(6)
      carboxyfluorescein and fluorescein were incorporated into the nanoparticles and
      their release profiles were recorded at 60 degrees C and at 37 degrees C for
      rhodamine 6G, for nanoparticles with a multilayer coating, and those that were
      crosslinked and grafted with PEG.

PMID- 19089872
TI  - Biodegradable multiblock copolymers based on oligodepsipeptides with shape-memory
      properties.
AB  - Thermoplastic phase-segregated multiblock copolymers with polydepsipeptides and
      PCL segments were prepared via coupling of diol and PCL-diol using an aliphatic
      diisocyanate. The obtained multiblock copolymers showed good elastic properties
      and a shape memory. Almost complete fixation of the mechanical deformation,
      resulting in quantitative recovery of the permanent shape with a switching
      temperature around body temperature, was observed. In hydrolytic degradation
      experiments, a quick decrease of the molecular weight without induction period
      was observed, and the material changed from elastic to brittle in 21 d. These
      materials promise a high potential for biomedical applications such as smart
      implants or medical devices.

PMID- 19089874
TI  - Assessment of the extent of starch dissolution in dimethyl sulfoxide by 1H NMR
      spectroscopy.
AB  - Complete dissolution is needed for the separation, characterization, or
      homogeneous labeling of whole starch molecules. A method is presented to quantify
      the extent of starch dissolution in DMSO for the first time; it is validated on a
      commercial rice starch. It is used directly on starch dispersions containing
      possible undissolved or co-dissolved species. High-amylose maize starches, known
      to be digested slowly in vivo, only quantitatively dissolve in the presence of
      high concentrations of an H-bond disrupter, LiBr, although they form clear
      dispersions at low LiBr concentrations. Starch quantitatively dissolves from waxy
      rice flours; non-starch components partially co-dissolve but do not interfere
      with the dissolution quantification.

PMID- 19089873
TI  - Hybrid microgels with antibacterial properties.
AB  - In the present work, we have used aqueous microgels as containers for the
      deposition of silver nanoparticles (AgNPs). It has been shown that AgNPs can be
      effectively incorporated in the microgel interior during the in situ reduction of
      silver ions. Obtained hybrid microgels with variable AgNPs loading (from 1 to 12
      wt.-%) have been used as antibacterial agents for two bacteria types. The
      experimental results indicate that porous microgel structure allows the release
      of the silver ions from the AgNPs surface into an aqueous phase. This ensures
      effective reduction in the number of bacterial colonies in test plates and
      complete bacteria killing. The antibacterial efficiency of the microgel particles
      increases with AgNPs loading.

PMID- 19089875
TI  - Evaluation of a home-based exercise program in the treatment of Alzheimer's
      disease: the Maximizing Independence in Dementia (MIND) study.
AB  - OBJECTIVE: To determine the feasibility and efficacy of a home-based exercise
      intervention program to improve the functional performance of patients with
      Alzheimer's Disease (AD). METHODS: Twenty-seven home-dwelling patients with AD
      were randomized to either an exercise intervention program delivered by their
      caregivers or a home safety assessment control. Measures of functional
      performance (primary), cognition, neuropsychiatric symptoms, quality of life and
      caregiver burden (secondary) were obtained at baseline and at 6 and 12 weeks
      following randomization. For each outcome measure, intent-to-treat analyses using
      linear random effects models were performed. Feasibility and adverse events were
      also assessed. RESULTS: Adherence to the exercise program was good. On the
      primary outcomes (functional performance) patients in the exercise group
      demonstrated a trend for improved performance on measures of hand function and
      lower extremity strength. On secondary outcome measures, trends toward worse
      depression and lower quality of life ratings were noted. CONCLUSIONS: The
      physical exercise intervention developed for the study, delivered by caregivers
      to home-dwelling patients with AD, was feasible and was associated with a trend
      for improved functional performance in this group of frail patients. Given the
      limited efficacy to date of pharmacotherapies for AD, further study of exercise
      intervention, in a variety of care setting, is warranted.

PMID- 19089877
TI  - Exploring the structural complexities of metal-metalloid nanoparticles: the case
      of Ni.B as catalyst.
AB  - Understanding of the structural complexities of metal-metalloid nanoparticles is
      at the heart of several proposals for investigating the physical properties and
      practical applications of these bi-elemental nanomaterials. To date, the most
      widely studied metal-metalloid is the nickel-boron (Ni.B) system; however, the
      exact nature of the structure of the material itself has remained unclear. Herein
      we show our systematic investigations of the material in an attempt to reveal its
      fascinating nanostructure. The relation between its high catalytic activity and
      the ultrafine structure is explored, and the work has been further extended to
      the formation of colloidal Ni.B nanoparticles. The results presented in this work
      may represent a substantial progress toward a full understanding of the nickel
      boron chemistry.

PMID- 19089876
TI  - Screening for dyslexia, dyspraxia and Meares-Irlen syndrome in higher education.
AB  - This study reports a comparison of screening tests for dyslexia, dyspraxia and
      Meares-Irlen (M-I) syndrome in a Higher Education setting, the University of
      Worcester. Using a sample of 74 volunteer students, we compared the current tutor
      delivered battery of 15 subtests with a computerized test, the Lucid Adult
      Dyslexia Screening test (LADS), and both of these with data on assessment
      outcomes. The sensitivity of this tutor battery was higher than LADS in
      predicting dyslexia, dyspraxia or M-I syndrome (91% compared with 66%) and its
      specificity was lower (79% compared with 90%). Stepwise logistic regression on
      these tests was used to identify a better performing subset of tests, when
      combined with a change in practice for M-I syndrome screening. This syndrome
      itself proved to be a powerful discriminator for dyslexia and/or dyspraxia, and
      we therefore recommend it as the first stage in a two-stage screening process.
      The specificity and sensitivity of the new battery, the second part of which
      comprises LADS plus four of the original tutor delivered subtests, provided the
      best overall performance: 94% sensitivity and 92% specificity. We anticipate that
      the new two-part screening process would not take longer to complete.

PMID- 19089878
TI  - Phase behavior in blends of ethylene oxide-propylene oxide copolymer and
      poly(ether sulfone) studied by modulated-temperature DSC and NMR relaxometry.
AB  - The state diagram of a blend consisting of a copolymer containing ethylene oxide
      and propylene oxide, P(EO-ran-PO), and poly(ether sulfone), PES, is constructed
      by using modulated-temperature differential scanning calorimetry (MTDSC), T(2)
      NMR relaxometry, and light scattering. The apparent heat capacity signal in MTDSC
      is used for the characterization of polymer miscibility and morphology
      development. T(2) NMR relaxometry is used to detect the onset of phase
      separation, which is in good agreement with the onset of phase separation in the
      apparent heat capacity from MTDSC and the cloud-point temperature as determined
      from light scattering. The coexistence curve can be constructed from T(2) values
      at various temperatures by using a few blends with well-chosen compositions.
      These T(2) values also allow the detection of the boundary between the demixing
      zones with and without interference of partial vitrification and are in good
      agreement with stepwise quasi-isothermal MTDSC heat capacity measurements.
      Important interphases are detected in the heterogeneous P(EO-ran-PO)/PES blends.

PMID- 19089879
TI  - trans-cis photoisomerization of azobenzene-conjugated dithiolato-bipyridine
      platinum(II) complexes: extension of photoresponse to longer wavelengths and
      photocontrollable tristability.
AB  - Azobenzene derivatives modified with dithiolato-bipyridine platinum(II) complexes
      were synthesized, revealing their highly extended photoresponses to the long
      wavelength region as well as unique photocontrollable tristability. The
      absorptions of trans-1 and trans-2 with one azobenzene group on the dithiolene
      and bipyridine ligands, respectively, cover the range from 300 to 700 nm. These
      absorptions are ascribed, by means of time-dependent (TD)DFT calculations, to
      transitions from dithiolene(pi) to bipyridine(pi*), namely, interligand charge
      transfer (CT), pi-pi*, and n-pi* transitions of the azobenzene unit, and pi-pi*
      transitions of the bipyridine ligand. In addition, only trans-1 shows distinctive
      electronic bands, assignable to transitions from the dithiolene(pi) to
      azobenzene(pi*), defined as intraligand CT. Complex 1 shows photoisomerization
      behavior opposite to that of azobenzene: trans-to-cis and cis-to-trans
      conversions proceed with 405 and 312 nm irradiation, which correspond to
      excitation with the intraligand CT, and pi-pi* bands of the azobenzene and
      bipyridine units, respectively. In contrast, complex 2 shows photoisomerization
      similar to that of azobenzene: trans-to-cis and cis-to-trans transformations
      occur with 365 and 405 nm irradiation, respectively. Irradiation at 578 nm,
      corresponding to excitation of the interligand CT transitions, results in cis-to
      trans conversion of both 1 and 2, which is the longest wavelength ever reported
      to effect the photoisomerization of the azobenzene group. The absorption and
      photochromism of 4, which has azobenzene groups on both the dithiolato and
      bipyridine ligands, have characteristics quite similar to those of 1 and 2, which
      furnishes 4 with photocontrollable tristability in a single molecule using light
      at 365, 405, and 578 nm. We also clarified that 1 and 2 have high
      photoisomerization efficiencies, and good thermal stability of the cis forms.
      Complexes 3 and 5 have almost the identical photoresponse to those of their
      positional isomers, complexes 2 and 4.

PMID- 19089880
TI  - Spin crossover in a family of iron(II) complexes with hexadentate ligands: ligand
      strain as a factor determining the transition temperature.
AB  - This paper reports the synthesis of a family of mononuclear complexes [Fe(L)]X(2)
      (X=BF(4), PF(6), ClO(4)) with hexadentate ligands L=Hpy-DAPP ({bis[N-(2
      pyridylmethyl)-3-aminopropyl](2-pyridylmethyl)amine}), Hpy-EPPA ({[N-(2
      pyridylmethyl)-3-aminopropyl][N-(2-pyridylmethyl)-2-aminoethyl](2
      pyridylmethyl)amine}) and Hpy-DEPA ({bis[N-(2-pyridylmethyl)-2-aminoethyl](2
      pyridylmethyl)amine}). The systematic change of the length of amino-aliphatic
      chains in these ligands results in chelate rings of different size: two six
      membered rings for Hpy-DAPP, one five- and one six-membered rings for Hpy-EPPA,
      and two five-membered rings for Hpy-DEPA. The X-ray analysis of three low-spin
      complexes [Fe(L)](BF(4))(2) revealed similarities in their molecular and crystal
      structures. The magnetic measurements have shown that all synthesized complexes
      display spin-crossover behavior. The spin-transition temperature increases upon
      the change from six-membered to five-membered chelate rings, clearly
      demonstrating the role of the ligand strain. This effect does not depend on the
      nature of the counter ion. We discuss the structural features accountable for the
      strain effect on the spin-transition temperature.

PMID- 19089881
TI  - The metallothionein/thionein system: an oxidoreductive metabolic zinc link.
AB  - Metallothioneins (MTs) were discovered more than 50 years ago and identified as
      low-molecular weight, sulfhydryl-rich proteins that were subsequently found to
      bind zinc predominantly. The binding of seemingly redox inactive zinc ions allows
      MT to play a central role in oxidoreductive cellular metabolism, cellular zinc
      distribution and homeostasis. In this interpretive study, we discuss the
      interaction of MT with physiologically relevant molecules and its effect on zinc
      thiolate bonds. These interactions are linked to recent progress in the
      functional role of MT in cellular zinc transport, energy production, and
      protection of the organism against oxidative stress and neurodegenerative
      diseases.

PMID- 19089882
TI  - Biological implications of the ribosome's stunning stereochemistry.
AB  - The ribosome's striking architecture is ingeniously designed for its efficient
      polymerase activity in the biosynthesis of proteins, which is a prerequisite for
      cell vitality. This elaborate architecture is comprised of a universal
      symmetrical region that connects all of the ribosomal functional centers involved
      in protein biosynthesis. Assisted by the mobility of selected ribosomal
      nucleotides, the symmetrical region provides the structural tools that are
      required not only for peptide bond formation, but also for fast and smooth
      successive elongation of nascent proteins. It confines the path along which the A
      tRNA 3'-end is rotated into the P-site in concert with the overall tRNA/mRNA
      sideways movement, thus providing the required stereochemistry for peptide bond
      formation and substrate-mediated catalysis. The extreme flexibility of the
      nucleotides that facilitate peptide bond formation is being exploited to promote
      antibiotic selectivity and synergism, as well as to combat antibiotic resistance.

PMID- 19089883
TI  - NMR spectroscopic characterization of inclusion complexes comprising
      cyclodextrins and gallated catechins in aqueous solution: cavity size dependency.
AB  - The structure of inclusion complexes of gamma-cyclodextrin (gamma-CD), (-)
      gallocatechin gallate (GCg), and (-)-epigallocatechin gallate (EGCg) in D(2)O was
      investigated using several NMR techniques. GCg formed a 1:1 inclusion complex
      with gamma-CD in which the A and C rings of GCg were inserted deep at the head of
      the A ring into the gamma-CD cavity from the wide secondary hydroxyl group side.
      In the 1:1 inclusion complex with GCg and gamma-CD, the GCg moiety maintained a
      conformation in which the B and B' rings of GCg took both pseudoequatorial
      positions with respect to the C ring. The structure of the inclusion complex of
      GCg and gamma-CD obtained from NMR experiments supported well that determined
      from PM6 semiempirical SCF MO calculations. However, (1)H NMR experiments
      suggested that EGCg did not form any inclusion complex with gamma-CD in D(2)O.
      The marked difference between GCg and EGCg in inclusion behavior toward gamma-CD
      may be explained in terms of the stabilization energy calculated with the PM6
      method. .

PMID- 19089884
TI  - Mathematics anxiety in secondary students in England.
AB  - Whatever the changes that are made to the mathematics curriculum in England,
      there will always remain a problem with mathematics anxiety. Maths anxiety is
      rarely facilitative. This study examined aspects of mathematics in secondary
      schools and how students rated them as sources of anxiety. Over 2000 students in
      independent and mainstream schools in England completed a 20-item questionnaire
      designed to investigate maths anxiety levels. The same questionnaire was given to
      over 440 dyslexic males in specialist schools within the same age range. The
      results showed that examinations and tests create high levels of anxiety in
      approximately 4% of students. The results suggest that certain aspects and topics
      in the maths curriculum, such as long division, cause similar levels of anxiety
      for students in all year groups in secondary schools.

PMID- 19089885
TI  - (1)H and (13)C NMR assignments for two new steroids from the coral Chromonephthea
      sp.
AB  - Two new steroids isolated from EtOH extracts of the South China Sea soft coral
      Chromonephthea sp. were identified. One-dimensional (1D) and two-dimensional (2D)
      NMR experiments including COSY, HSQC, HMBC and NOESY were used for the
      determination of their structure.

PMID- 19089886
TI  - A bagging-based correction for the mixture model estimator of population size.
AB  - Estimation of a population size by means of capture-recapture techniques is an
      important problem occurring in many areas of life and social sciences. We
      consider the frequencies of frequencies situation, where a count variable is used
      to summarize how often a unit has been identified in the target population of
      interest. The distribution of this count variable is zero-truncated since zero
      identifications do not occur in the sample. As an application we consider the
      surveillance of scrapie in Great Britain. In this case study holdings with
      scrapie that are not identified (zero counts) do not enter the surveillance
      database. The count variable of interest is the number of scrapie cases per
      holding. For count distributions a common model is the Poisson distribution and,
      to adjust for potential heterogeneity, a discrete mixture of Poisson
      distributions is used. Mixtures of Poissons usually provide an excellent fit as
      will be demonstrated in the application of interest. However, as it has been
      recently demonstrated, mixtures also suffer under the so-called boundary problem,
      resulting in overestimation of population size. It is suggested here to select
      the mixture model on the basis of the Bayesian Information Criterion. This
      strategy is further refined by employing a bagging procedure leading to a series
      of estimates of population size. Using the median of this series, highly
      influential size estimates are avoided. In limited simulation studies it is shown
      that the procedure leads to estimates with remarkable small bias.

PMID- 19089887
TI  - Expression of orexin A and its receptor 1 in the vestibular glands of the cattle
      genital tract.
AB  - The hypothalamic peptide orexin A (oxA) binds specifically the G-protein-coupled
      orexin receptor 1 (ox1R). It is involved in many physiological functions
      including the regulation of food intake, sleep-wake cycle, arterial blood
      pressure, heart rate, and sexual behavior. The localization of oxA in adrenal
      glands, stomach, bowel, pancreas, and testis has recently been assessed. Here, we
      provide the first evidence for the expression of oxA and ox1R in the vestibular
      glands of mammalian genital tract.

PMID- 19089888
TI  - Embryonic staging system for the Black Mastiff Bat, Molossus rufus (Molossidae),
      correlated with structure-function relationships in the adult.
AB  - An embryonic staging system for Molossus rufus (also widely known as Molossus
      ater) was devised using 17 reference specimens obtained during the
      postimplantation period of pregnancy from wild-caught, captive-bred females. This
      was done in part by comparing the embryos to a developmental staging system that
      had been created for another, relatively unrelated bat, Carollia perspicillata
      (family Phyllostomidae). Particular attention was paid to the development of
      species-specific features, such as wing and ear morphology, and these are
      discussed in light of the adaptive significance of these structures in the adult.
      M. rufus can be maintained and bred in captivity and is relatively abundant in
      the wild. This embryonic staging system will facilitate further developmental
      studies of M. rufus, a model species for one of the largest and most successful
      chiropteran families, the Molossidae.

PMID- 19089889
TI  - Von Economo neurons in the elephant brain.
AB  - Von Economo neurons (VENs), previously found in humans, all of the great ape
      species, and four cetacean species, are also present in African and Indian
      elephants. The VENs in the elephant are primarily found in similar locations to
      those in the other species. They are most abundant in the frontoinsular cortex
      (area FI) and are also present at lower density in the anterior cingulate cortex.
      Additionally, they are found in a dorsolateral prefrontal area and less
      abundantly in the region of the frontal pole. The VEN morphology appears to have
      arisen independently in hominids, cetaceans, and elephants, and may reflect a
      specialization for the rapid transmission of crucial social information in very
      large brains.

PMID- 19089890
TI  - Randomized comparison of tolterodine with vaginal estrogen cream versus
      tolterodine alone for the treatment of postmenopausal women with overactive
      bladder syndrome.
AB  - AIMS: To investigate whether vaginal estrogen cream combined with tolterodine is
      more effective than tolterodine alone in the treatment of postmenopausal women
      with overactive bladder (OAB). MATERIALS AND METHODS: This is an unblinded study
      without placebo. A preliminary study consisted of tolterodine 2 mg twice per day
      for 3 months had been conducted for 25 postmenopausal women with OAB. Over a
      period of 11 months, 80 postmenopausal women with OAB underwent a prospective
      randomized trial. These patients were equally randomized into two groups. The
      interventions for the 12-week treatment period included 2 mg tolterodine twice
      per day for the group A and 2 mg tolterodine twice per day/vaginal conjugated
      equine estrogen 0.625 mg twice a week for the group B. Identical pre- and post
      treatment assessments included bladder diary, Urogenital Distress Inventory-6
      (UDI-6), and Incontinence Impact Questionnaire-7 (IIQ-7). RESULTS: All 80 women
      (65.2 years, range 58-73) completed this study. The between groups comparison
      showed that the group B had significant improvements in mean daytime frequency
      and voided volume after treatment (14.8-5.8 vs. 14.1-6.4, P = 0.001 and 115.8
      141.9 vs. 108.5-134.5, P = 0.007, respectively). Additionally, a comparison of
      the final total scores of UDI-6 and IIQ-7 between the two groups revealed that
      the group B had a statistically significant improvement in quality of life than
      that in the group A (8.6-6.9 vs. 9.5-7.2, P < 0.001 and 9.4-6.1 vs. 10.2-6.5, P <
      0.001, respectively). Changes in the other symptoms, including nocturia, urgency
      and urge incontinence, were not statistically significant but actually achieved
      improved in both groups. CONCLUSIONS: A combination of vaginal estrogen cream and
      tolterodine is a potential therapy for postmenopausal women with OAB.

PMID- 19089891
TI  - Urinary nerve growth factor levels are elevated in patients with overactive
      bladder and do not significantly increase with bladder distention.
AB  - AIMS: Urinary nerve growth factor (NGF) levels have been found to be higher in
      patients with overactive bladder (OAB) compared to normal controls. This study
      investigated the effect of bladder volume on urinary NGF production in normal
      controls and patients with OAB. METHODS: Urinary NGF levels were measured in 39
      patients with OAB and in 35 control subjects without lower urinary tract symptoms
      (LUTS). Urine samples were collected at the first sensation of bladder filling
      (FSF) and at urge sensation (US), respectively, in both groups. Measurement of
      urinary NGF levels was performed by ELISA method and normalized by urinary
      creatinine concentration (NGF/Cr). The correlation between NGF/Cr level and
      increased bladder volume was analyzed. RESULTS: Urinary NGF/Cr levels in normal
      controls were very low at FSF (mean +/- standard error, 0.011 +/- 0.008) and were
      significantly higher at US (0.086 +/- 0.022, P = 0.005). Patients with OAB had
      significantly higher urinary NGF/Cr levels both at FSF (0.45 +/- 0.13, P = 0.001)
      and US (1.00 +/- 0.32, P = 0.004) compared to controls. The difference in urinary
      NGF/Cr levels between FSF and US in OAB patients, however, was not significant (P
      = 0.064). CONCLUSIONS: Urinary NGF/Cr level was well correlated with bladder
      volume at US in the controls but not significant associated with bladder volume
      increase in patients with OAB. The results of this study suggest urinary NGF
      increases physiologically in normal subjects at urge to void but is
      pathologically elevated in OAB patients at small bladder volume and does not
      significantly increase at urgency sensation.

PMID- 19089892
TI  - Lower urinary tract dysfunction in familial amyloidotic polyneuropathy,
      Portuguese type.
AB  - AIM: Study lower urinary dysfunction in familial amyloidotic polyneuropathy
      (FAP). METHODS: Fifty-four FAP patients were studied. Clinical examination,
      urodynamics and ultrasound of the urinary tract were performed. RESULTS: Urinary
      symptoms appeared during the first three years of the disease in 50% of the
      patients. The initial urinary symptom was dysuria in 39% and incontinence in 24%
      of the patients, sensitivity and contractility disturbances of the detrusor were
      found at the initial stages. Non-relaxing urethral sphincter was found in 51,7%
      and dyssynergia in 37,5% of the cases. Ultrasound revealed thickening of the
      vesical wall in 42,5% of the patients, more common in males (M:16; F:7). Opening
      of the vesical neck was found in 56% of the cases (M:19; F:11) with paradoxical
      closure during the attempt to void. Fluctuations in the opening of the vesical
      neck were found in eight patients, also more frequently in males (M:6; F:2).
      CONCLUSIONS: In addition to reduced sensation, underactive detrusor, opening of
      the vesical neck and external sphincter deficit, we found data suggesting failure
      of relaxation of the internal and external sphincter. The overdistention
      associated with an open vesical neck and external sphincter deficit justifies
      incontinence in those patients. The retention is due to inadequate contraction of
      the detrusor, probably associated with non-relaxing of the internal and external
      sphincter. These dysfunctions derive from deposition of amyloid substance in the
      detrusor, but overdistention is likely to play a role. Early therapeutic
      intervention in these patients is vital to avoid secondary injuries.

PMID- 19089893
TI  - Tectotectal neurons and projections: a proposal to establish a consistent
      nomenclature.

PMID- 19089894
TI  - Goal achievement provides new insights into interstitial cystitis/painful bladder
      syndrome symptoms and outcomes.
AB  - AIMS: Goal Assessment Scaling (GAS), wherein patients specify goals then evaluate
      treatments with regard to goal achievement, has proven utility in assessing
      treatment of complex conditions such as chronic pain, rheumatoid arthritis, and
      incontinence. We used surveys and focus groups to characterize the goals of
      patients with interstitial cystitis/painful bladder syndrome (IC/PBS) in order to
      create a pilot GAS. METHODS: 37 patients with IC/PBS recorded and ranked their
      treatment goals which were pooled and analyzed for emergent domains and priority
      rankings. 15 patients participated in 3 separate focus groups. Focus group
      audiotapes were transcribed and reviewed to identify major themes and goals
      domains. RESULTS: 140 separate goals were collected. Mean number of goals 4+/
      2.73% had pain goals and 56% had frequency and/or nocturia goals. Focus groups
      revealed that urgency is a separate entity from pain or frequency and any of
      these may take priority. The groups defined urgency for IC/PBS patient as "the
      need to urinate due to an unpleasant sensation that prevents attention to any
      other task." Additional goal domains of control, predictability, and information
      were explored. Unsatisfactory aspects of common urological surveys were discussed
      as well as positive and negative aspects of GAS. CONCLUSIONS: Patients have
      individualized treatment goals. GAS holds promise for addressing individuality in
      a standardized format. A new instrument developed from this work is being piloted
      in a multicenter RCT. We also suggest that questionnaires investigating urgency
      in IC/PBS clarify the definition in a way more applicable to the specific
      condition.

PMID- 19089895
TI  - What's hot from the ICS annual meeting 2008.

PMID- 19089896
TI  - Pigmentation in anuran testes: anatomical pattern and variation.
AB  - In amphibians, pigmented cells are present in several organs, composing an
      extracutaneous pigmentary system. Seventeen species from two families were
      studied to develop a protocol for pigmentary classification. The amount and
      distribution of these cells are variable, allowing the establishment of
      anatomical patterns for visceral pigmentation in anuran testes.

PMID- 19089897
TI  - Modulation of diabetes-induced palate defects by maternal immune stimulation.
AB  - Maternal diabetes can induce a number of developmental abnormalities in both
      laboratory animals and humans, including deformities of the face and palate. The
      incidence of birth defects in newborns of women with diabetes is approximately 3
      to 5 times higher than among nondiabetics. In mice, nonspecific activation of the
      maternal immune system can reduce fetal abnormalities caused by various
      etiologies including hyperglycemia. This study was conducted to determine whether
      nonspecific maternal immune stimulation could reduce diabetes-induced palate
      defects and orofacial clefts. Female ICR mice were immune stimulated before
      induction of hyperglycemia with Freund's complete adjuvant (FCA), granulocyte
      macrophage colony-stimulating factor (GM-CSF), or interferon-gamma (IFNgamma).
      Streptozocin was used to induce hyperglycemia (26-35 mmol blood glucose) in
      females before breeding. Fetuses from 12 to 18 litters per treatment group were
      collected on Day 17 of gestation. Palate width and length were measured, and the
      incidence of orofacial clefts was determined. Palate length and width were both
      decreased by maternal hyperglycemia. Maternal immune stimulation with GM-CSF or
      FCA limited the degree of palate shortening from the hyperglycemia. Each of the
      three immune stimulants attenuated significant narrowing of the palate. Rates of
      orofacial clefts were not significantly different between treatment groups.
      Palatogenesis is a complex process driven by cellular signals, which regulate
      cell growth and apoptosis. Dysregulation of cellular signals by maternal
      hyperglycemia can result in fetal malformations. Maternal immune stimulation may
      prevent dysregulation of these signaling pathways thus reducing fetal
      malformations and normalizing palate growth.

PMID- 19089898
TI  - Pre-operative opening detrusor pressure is predictive of detrusor overactivity
      following TVT in patients with pre-operative mixed urinary incontinence.
AB  - AIMS: To determine if specific pre-operative urodynamic parameters could predict
      detrusor overactivity following TVT in patients with urodynamic mixed
      incontinence. METHODS: Notes of women with detrusor overactivity (DO) and
      urodynamic stress incontinence (USI) before undergoing tension-free vaginal tape
      (TVT) surgery were retrospectively reviewed. Patients underwent clinical
      evaluation pre-operatively including history, examination, and conventional
      urodynamic studies and were treated with pelvic floor exercises and anti
      cholinergic medication. Those with persistent stress urinary incontinence (SUI)
      underwent TVT. Patients were re-assessed after at least 6 months post
      operatively. Pre- and post-operative opening and closing detrusor pressure, and
      detrusor pressure at maximum flow were recorded retrospectively from pre
      operative urodynamics traces by two clinicians independently and compared to the
      patients' post-operative symptoms and urodynamic diagnosis. RESULTS: Fifty-one
      women were reviewed. Forty-six of the 51 attended follow-up and 35/51 agreed to
      conventional urodynamic studies. Seventeen of the 35 reported OAB symptoms, and
      18/35 were asymptomatic. Nineteen of the 35 women had DO and 16/35 had normal
      urodynamic studies (NUDS). The median pre-operative opening detrusor pressure was
      higher in women with overactive bladder symptoms post-operatively. The median pre
      operative opening detrusor pressure in women with DO post-operatively was 33.0
      cmH(2)O and the median pre-operative opening detrusor pressure in those with NUDS
      post-operatively was 16 cmH(2)O (15.0-23.0 cmH(2)O) (P < 0.05 Mann-Whitney U
      test). CONCLUSIONS: Higher numbers of patients are required to demonstrate the
      value of opening detrusor pressure in predicting post-operative overactive
      bladder symptoms. Opening detrusor pressure is predictive of post-operative DO
      after TVT.

PMID- 19089899
TI  - Re: Laparoscopic versus colposuspension for urodynamic stress incontinence by Tan
      et al. Vol. 26(2) March 2007.

PMID- 19089901
TI  - The stem cell niche.
AB  - Virtually every tissue of the adult organism maintains a population of putatively
      slowly-cycling stem cells that maintain homeostasis of the tissue and respond to
      injury when challenged. These cells are regulated and supported by the
      surrounding microenvironment, referred to as the stem cell 'niche'. The niche
      includes all cellular and non-cellular components that interact in order to
      control the adult stem cell, and these interactions can often be broken down into
      one of two major mechanistic categories--physical contact and diffusible factors.
      The niche has been studied directly and indirectly in a number of adult stem cell
      systems. Herein, we will first focus on the most well-understood niches
      supporting the germline stem cells in the lower organisms Caenorhabditis elegans
      and Drosophila melanogaster before concentrating on the more complex, less well
      understood mammalian niches supporting the neural, epidermal, haematopoietic and
      intestinal stem cells.

PMID- 19089902
TI  - Aquaporin-4 overexpression in rat ALS model.
AB  - Onset of motoneuron death characterizing amyotrophic lateral sclerosis (ALS) is
      closely linked to modified astrocytic and glial environments. Here, we show that
      in the spinal cord from transgenic rat overexpressing mutated human SOD1,
      aquaporin-4 mRNA and protein are specifically overexpressed in the gray matter at
      end stage of disease. Immunohistochemistry and double immunofluorescence allowed
      to detect, in the spinal cord gray matter of the ALS rat, increased aquaporin-4
      surrounding both vessel and motoneuron perikarya. The use of pre-embedding
      immunohistochemistry at electron microscopic level confirmed such localization
      associated with swollen astrocytic processes surrounding the vessels. The AQP4
      immunohistochemical labeling surrounding several motoneuron perikarya was only
      seen in ALS rats. Identification of this AQP4-positive cellular type remains
      unclear.

PMID- 19089903
TI  - New insights into the neuromuscular anatomy of the ileocecal valve.
AB  - The neuroanatomy of the ileocecal valve (ICV) is poorly understood. A better
      understanding of this important functional component of the gastrointestinal
      tract would enable surgeons to reconstruct an effective valve following surgical
      resection of the ICV. ICVs were examined in young pigs (N = 5) using frontal and
      transverse paraffin embedded and frozen sections. Hematoxylin+Eosin (H+E)
      staining, acetylcholinesterase (AchE), and NADPH-diaphorase (NADPH-d)
      histochemistry and protein gene product 9.5 (PGP 9.5) and C-kit
      immunohistochemistry were performed. The H+E staining revealed that the ICV
      consists of three muscle layers: an external circular muscle layer continuous
      with that of the ileal circular muscle layer, an inner circular muscle layer
      continuous with that of the cecal circular muscle layer, and a single
      longitudinal muscle layer, which appears to be secondary to a fusion of the ileal
      and cecal longitudinal muscle layers. The AchE, NADPH-d, and PGP 9.5 staining
      revealed two distinct coaxial myenteric plexuses, together with superficial and
      deep submucosal plexuses. The C-kit immunostaining showed a continuous myenteric
      ICC network within the ICV. The structure of the neuromuscular components within
      the ICV suggests that the valve is a result of a simple intussusception of the
      terminal ileum into the cecum. This knowledge may help surgeons in their future
      attempts at reconstructing more anatomically and functionally suitable ICVs
      following surgical resection of native ICVs.

PMID- 19089904
TI  - Phenotypic plasticity and function of the hard palate in growing rabbits.
AB  - Morphological variation related to differential loading is well known for many
      craniomandibular elements. Yet, the function of the hard palate, and in
      particular the manner in which cortical and trabecular bone of the palate respond
      to masticatory loads, remains more ambiguous. Here, experimental data are
      presented that address the naturalistic influence of biomechanical loading on the
      postweaning development and structure of the hard palate. A rabbit model was used
      to test the hypothesis that variation in the morphology of the hard palate is
      linked to variation in masticatory stresses. Rabbit siblings were divided as
      weanlings into soft and hard/tough dietary treatment groups of 10 subjects each
      and were raised for 15 weeks until subadulthood. MicroCT analyses indicate that
      rabbits subjected to elevated masticatory loading developed hard palates with
      significantly greater bone area, greater cortical bone thickness along the oral
      lamina, and thicker anterior palates. Such diet-induced levels of palatal
      plasticity are comparable to those for other masticatory elements, which likely
      reflect osteogenic responses for maintaining the functional integrity of the
      palate vis-a-vis elevated stresses during unilateral mastication. These data
      support a role for mechanical loading in the determination of palatal morphology,
      especially its internal structure, in living and fossil mammals such as the
      hominin Paranthropus. Furthermore, these findings have potential implications for
      the evolution of the mammalian secondary hard palate as well as for clinical
      considerations of human oral pathologies.

PMID- 19089905
TI  - Ultrastructural morphology and morphometry of phrenic nerve in rats.
AB  - Despite numerous literature reports on the morphometry of the myelinated fibers
      of phrenic nerves in rats, a systematic study of the longitudinal and lateral
      symmetry of the unmyelinated fibers morphometry is not available. In this study,
      we have undertaken ultrastructural and morphometric studies of the phrenic nerve
      in adult rats, assessing two different levels (proximal and distal) from both
      right and left sides. Phrenic nerves of adult male Wistar rats were prepared for
      epoxy resin embedding and transmission electron microscopy. Morphometric analysis
      was performed with the aid of computer software, which took into consideration
      the unmyelinated fiber number, density, area, and diameter, as well as ratio
      between myelinated and unmyelinated fibers, and the percentage of the fascicular
      area occupied by the myelinated and unmyelinated fibers. Comparison of data from
      proximal and distal segments on the same side and from the same levels between
      sides was performed. Differences were considered significant when P < 0.05. The
      most important finding is that morphometric parameters of the phrenic nerve
      unmyelinated fibers in adult rats are both longitudinally and laterally
      symmetric. This study adds important morphometric information about the
      unmyelinated fibers of the phrenic nerves in adult rats for proximal and distal
      levels on both sides of the animal.

PMID- 19089906
TI  - Assessment of axonal growth into collagen nerve guides containing VEGF
      transfected stem cells in matrigel.
AB  - The early events associated with axonal growth into 10-mm nerve gaps were studied
      histologically in the rat sciatic nerve model to determine if the outgrowth of
      blood vessels, Schwann cells, and axons could be enhanced. In the first two
      experimental groups, collagen nerve guides were filled with either saline or
      Matrigel. Marrow-derived mesenchymal stem cells (MSCs) were added to Matrigel in
      two other groups, one of which contained cells transfected with VEGF (MSC/VEGF).
      After 21 days, the injury site was exposed, fixed, sectioned, and volume
      fractions of the conduit contents were determined by point counting. The
      bioresorbable collagen conduits appropriately guided the axons and vessels in a
      longitudinal direction. The volume fraction of axons was significantly greater in
      the group with saline when compared with all three groups with Matrigel. This
      measure had a significant positive correlation with actual counts of myelinated
      axons. The blood vessel volume fraction in the Matrigel group decreased compared
      with the saline group, but was restored in the MSC/VEGF group. All Matrigel
      groups had comparable cellularity and showed a distribution of residual Matrigel
      in acellular zones. The saline group, by contrast, sustained a network of
      delicate fibroblastic processes that compartmentalized the nerve and its natural
      matrix as it became infiltrated by axons as minifascicles. In conclusion, the
      reduction of axonal outgrowth in the Matrigel groups, when compared with the
      saline group, suggests that Matrigel may impede the early regenerative process
      even when enriched by the addition of MSCs or VEGF-transfected cells.

PMID- 19089908
TI  - Stem cells in pathobiology and regenerative medicine.
AB  - This issue of the Journal of Pathology contains 16 articles largely dealing with
      the role of tissue-specific adult stem cells in the pathogenesis of disease,
      notably cancer. These authoritative reviews begin by describing the current
      knowledge regarding the identity and molecular regulation of normal tissue
      specific stem cells, before itemizing their role in the aetiology and progression
      of disease. Fundamental concepts regarding the stem cell niche have been gleaned
      from studies of germ line stem cells in Drosophila and Caenorhabditis elegans,
      and these are described in detail in this issue. Somatic cell reprogramming, a
      process underlying not only therapeutic cloning but also the production of
      induced pluripotent stem (iPS) cells, is further discussed. Much attention is
      given to embryonic stem (ES) and iPS cells within the scientific community; this
      issue of the Journal of Pathology redresses this imbalance by illustrating the
      pivotal role of adult stem cells in much of human disease.

PMID- 19089910
TI  - Loss of EphA2 receptor tyrosine kinase reduces ApcMin/+ tumorigenesis.
AB  - The Eph receptor A2 (EphA2) is overexpressed in a range of human epithelial
      cancers, a phenotype that is associated with cancer cell proliferation,
      progression and angiogenesis. Mouse models of mammary neoplasia have confirmed
      the role of EphA2 as mice carrying a knockout allele of EphA2 were resistant to
      breast cancer, a phenotype that was associated with interactions between EphA2
      and ErbB2. We investigated in vivo the role of EphA2 in GI cancer. To determine
      whether EphA2 influences intestinal tumorigenesis, we used qRT-PCR to examine the
      mRNA expression levels of EphA2 in tumors from the small intestine and colon of
      Apc(Min/+) mice. We found that EphA2 was significantly up-regulated in tumors
      from both regions when compared with normal control tissues. We then evaluated
      the spatial expression patterns of EphA2 protein using immunohistochemistry in
      both the small intestine and colon and found that in normal tissues EphA2 was
      robustly expressed in highly differentiated cells, such as cells of the villi,
      but that EphA2 expression was largely absent from the stem cell niche and
      proliferative zones of intestinal crypts. In contrast, in tumors EphA2 was
      broadly expressed. Finally, we created a strain of Apc(Min/+) mice carrying a
      genetic knockout of the EphA2 gene. These mice developed significantly fewer and
      smaller tumors in both the small and large intestine. Overall, our results
      indicate that EphA2 plays an oncogenic role in the mammalian intestine suggesting
      that strategies to target EphA2 activity may offer new therapeutic modalities for
      colorectal cancer.

PMID- 19089909
TI  - HINT1 inhibits beta-catenin/TCF4, USF2 and NFkappaB activity in human hepatoma
      cells.
AB  - In this study we explored the relevance of Hint, a novel tumor suppressor gene,
      to human hepatoma. The human hepatoma cell lines Hep3B and HepG2 express very low
      levels of the HINT1 protein but the Huh7 cells express a relatively high level.
      In Hep3B and HepG2 cells, but not in Huh7 cells, the promoter region of Hint1 is
      partially methylated and treatment with 5-azadcdeoxycytidine increased expression
      of the HINT1 protein and Hint1 mRNA in Hep3B and HepG2 cells. Increased
      expression of HINT1 in HepG2 cells markedly inhibited their growth. It also
      inhibited the transcriptional activities of beta-catenin/TCF4, and USF2, and
      inhibited the expression of endogenous cyclin D1 and TGFbeta2. Furthermore, HINT1
      co-immunoprecipitated with USF2 in extracts of Hep2 cells. HINT1 also inhibited
      NFkappaB transcription factor reporter activity and inhibited translocation of
      the endogenous p65 protein to the nucleus of HepG2 cells. Therefore, decreased
      expression of the Hint1 gene through epigenetic silencing may play a role in
      enhancing the growth of a subset of human hepatoma by increasing the expression
      of genes controlled by the transcription factors beta-catenin, USF2, and
      NFkappaB.

PMID- 19089911
TI  - Inhibition of accelerated tumor growth by blocking the recruitment of mobilized
      endothelial progenitor cells after chemotherapy.
AB  - It has been suggested that immature progenitor cells mobilize from bone marrow
      into the peripheral blood in response to the chemotherapy-induced
      myelosuppression. We investigated how the mobilization of immature progenitor
      cells affects tumor growth after chemotherapy. We found significantly increased
      numbers of CD34(+)/Flk-1(+) endothelial progenitor cells in the peripheral blood
      of mice 1 week after the administration of 100 mg/kg cyclophosphamide vs. a
      saline injection (0.39 +/- 0.09% vs. 0.20 +/- 0.10%, respectively; p < 0.05).
      Tumor growth in the mice given chemotherapy was almost 1.3-fold faster than that
      in the mice given saline (268 +/- 66 mg vs. 210 +/- 3 5 mg, respectively; p <
      0.05). Histological examination of tumor tissue revealed significantly higher
      microvessel density and more Ki67-positive cells, but significantly fewer
      apoptotic cells, in the mice given chemotherapy than in those given saline (p <
      0.05). Furthermore, we detected significantly more bone marrow-derived cells,
      some of which stained positively for CD34 and were localized in the vessels, in
      tumor tissue from the mice given chemotherapy than in that from the mice given
      saline. However, the transient disruption of the SDF-1/CXCR4 axis by the antibody
      neutralization of CXCR4, which occurred over 1 week, blocked the recruitment of
      bone marrow-derived cells into the tumor tissue, and resulted in complete
      inhibition of accelerated tumor growth after chemotherapy. Our results show that
      chemotherapy induced the mobilization of endothelial progenitor cells and
      accelerated tumor growth, but that transient disruption of the SDF-1/CXCR4 axis
      could prevent accelerated tumor growth by blocking the recruitment of mobilized
      endothelial progenitor cells after chemotherapy.

PMID- 19089912
TI  - Activator protein 2 alpha (AP2alpha) suppresses 42 kDa C/CAAT enhancer binding
      protein alpha (p42(C/EBPalpha)) in head and neck squamous cell carcinoma.
AB  - The tumor suppressor C/CAAT enhancer binding protein alpha (C/EBPalpha) is a
      transcription factor involved in cell cycle control and cellular differentiation.
      A recent study showed that C/EBPalpha is frequently downregulated in head and
      neck squamous cell carcinoma (HNSCC) by DNA methylation in an upstream regulatory
      region. Here, we investigated how DNA methylation in the upstream regulatory
      region disrupts the transcriptional regulation of C/EBPalpha in HNSCC. The
      results reveal that aberrant methylation correlates with methyl binding domain
      protein binding and repressive histone modifications. This methylated region
      contains previously uninvestigated AP2alpha binding sites. AP2alpha suppresses
      C/EBPalpha promoter activity and protein expression. Interestingly, silencing
      AP2alpha by shRNA increases the antiproliferative isoform of C/EBPalpha
      (p42(C/EBPalpha)). Furthermore, growth analysis revealed that these 2 isoforms
      yield very different proliferative properties in HNSCC.

PMID- 19089914
TI  - Interferon-gamma down-regulates NKG2D ligand expression and impairs the NKG2D
      mediated cytolysis of MHC class I-deficient melanoma by natural killer cells.
AB  - NKG2D operates as an activating receptor on natural killer (NK) cells and
      costimulates the effector function of alphabeta CD8(+) T cells. Ligands of NKG2D,
      the MHC class I chain-related (MIC) and UL16 binding protein (ULBP) molecules,
      are expressed on a variety of human tumors, including melanoma. Recent studies in
      mice demonstrated that NKG2D mediates tumor immune surveillance, suggesting that
      antitumor immunity in humans could be enhanced by therapeutic manipulation of
      NKG2D ligand (NKG2DL) expression. However, signals and mechanisms regulating
      NKG2DL expression still need to be elucidated. Here, we asked whether the
      proinflammatory cytokine Interferon-gamma (IFN-gamma) affects NKG2DL expression
      in melanoma. Cell lines, established from MHC class I-negative and -positive
      melanoma metastases, predominantly expressed MICA and ULBP2 molecules on their
      surface. Upon IFN-gamma treatment, expression of MICA, in some cases, also of
      ULBP2 decreased. Besides melanoma, this observation was made also for glioma
      cells. Down-regulation of NKG2DL surface expression was dependent on the cytokine
      dose and the duration of treatment, but was neither due to an intracellular
      retention of the molecules nor to an increased shedding of ligands from the tumor
      cell surface. Instead, quantitative RT-PCR revealed a decrease of MICA-specific
      mRNA levels upon IFN-gamma treatment and siRNA experiments pointed to an
      involvement of STAT-1 in this process. Importantly, IFN-gamma-treated MHC class I
      negative melanoma cells were less susceptible to NKG2D-mediated NK cell
      cytotoxicity. Our study suggests that IFN-gamma, by down-regulating ligand
      expression, might facilitate escape of MHC class I-negative melanoma cells from
      NKG2D-mediated killing by NK cells.

PMID- 19089913
TI  - Circumcision and sexual behavior: factors independently associated with human
      papillomavirus detection among men in the HIM study.
AB  - There is growing interest in understanding human papillomavirus (HPV) infection
      and related disease among men. To date there have been numerous studies reporting
      HPV DNA prevalence among men from several different countries, however, few have
      incorporated multivariable analyses to determine factors independently associated
      with male HPV detection. The purpose of this study was to assess the factors
      independently associated with HPV detection in men ages 18-70 years residing in
      Brazil (n = 343), Mexico (n = 312), and the United States (US) (n = 333). In
      samples combined from the coronal sulcus, glans penis, shaft, and scrotum, we
      evaluated factors associated with any, oncogenic, and nononcogenic HPV
      infections. In multivariable analyses, detection of any HPV infection was
      significantly associated with reported race of Asian/Pacific Islander, lifetime
      and recent number of sexual partners, and having sex in the past 3 months.
      Oncogenic HPV detection was independently associated with lifetime and recent
      number of sexual partners, and having sex in the past 3 months. NonOncogenic HPV
      infection was independently associated with lifetime number of sexual partners.
      Circumcision, assessed by clinical examination, was associated with reduced risk
      of HPV detection across all categories of HPV evaluated. HPV detection in men in
      the current study was strongly related to sexual behavior and circumcision
      status. Interventions such as circumcision may provide a low-cost method to
      reduce HPV infection.

PMID- 19089915
TI  - Methionine depletion with recombinant methioninase: in vitro and in vivo efficacy
      against neuroblastoma and its synergism with chemotherapeutic drugs.
AB  - Methionine starvation can modulate gene methylation, cell cycle transition and
      pathways related to survival following DNA damage. Methionine depletion by
      recombinant methioninase (rMETase) may have in vitro and in vivo efficacy against
      neuroblastoma (NB), especially when combined with chemotherapeutic drugs. rMETase
      from Pseudomonas putida was produced in Escherichia coli and purified by ion
      exchange chromatography. rMETase alone inhibited the proliferation of 15/15 NB
      cell lines in vitro. Among these 15 cell lines, only 66N demonstrated rMETase
      induced apoptosis. rMETase alone suppressed LAN-1 and NMB-7 xenografts (p < 0.01)
      and no toxicities were noted other than reversible weight loss. In vitro efficacy
      experiments combining rMETase and chemotherapeutic agents were carried out using
      SK-N-LD and SK-N-BE (1)N established at diagnosis, as well as LAN-1, SK-N-BE (2)C
      and NMB-7 established at relapse. Microtubule depolymerization agents including
      vincristine, vinorelbine, vinblatine and mebendazole showed synergism when tested
      in combination with rMETase in all 5 cell lines. Among DNA damaging agents,
      synergy with rMETase was observed only in cell lines established at diagnosis and
      not at relapse. Cell cycle analysis showed that rMETase arrested G2 phase and not
      M phase. In vivo efficacy experiments using LAN-1 and NMB-7 xenografts showed
      that rMETase rendered vincristine more effective than vincristine alone in tumor
      growth suppression (p < 0.001). In conclusion, methionine depletion inhibited NB
      proliferation and arrested tumor cells at G2 phase. rMETase synergized with
      microtubule depolymerization agents. Moreover, synergism between rMETase and DNA
      damaging agents was dependent on whether cell lines were established at diagnosis
      or at relapse.

PMID- 19089917
TI  - Tumor-specific cytotoxic T cell generation and dendritic cell function are
      differentially regulated by interleukin 27 during development of anti-tumor
      immunity.
AB  - Interleukin (IL-) 27 is a member of IL-12 cytokine family with Th1-promoting and
      anti-inflammatory effects. IL-27 has been shown to facilitate tumor-specific
      cytotoxic T lymphocyte (CTL) induction against various tumors. However, IL-27
      suppresses cytokine production of lymphocytes and antigen-presenting function of
      dendritic cells (DCs). To examine the in vivo role of IL-27 in generation of anti
      tumor immunity, we examined IL-27-mediated antitumor-effects using WSX-1 (IL-27
      receptor alpha chain)-deficient (WSX-1(-/-)) mice. In WSX-1(-/-) mice inoculated
      with B16 melanoma cells, tumor growth was higher than in wild-type (WT) mice.
      Accordingly, tumor-specific CTL generation was lower in WSX-1(-/-) mice than in
      WT mice. CTL induction in WSX-1(-/-) mice was not restored by transfer of WT DCs
      pulsed with TRP2 peptide, indicating that IL-27 is directly required for
      generation of tumor-specific CTLs. However, when transferred into tumor-bearing
      mice, WSX-1(-/-) DCs pulsed with TRP2 peptide was more potent than WT DCs in
      tumor growth inhibition and generation of CTLs, indicating suppressive effects of
      IL-27 on DC function. Finally, the combination of WT CD8(+) T cells and KO DCs is
      more potent in generation of antigen-specific CTLs than any other combinations.
      Expression of perforin gene and percentages of tumor-specific CD8(+) T cells were
      also the highest in the combination of WT CD8+ T cells and WSX-1(-/-) DCs. It was
      thus revealed that IL-27 promotes CTL generation while suppressing DC function
      during generation of tumor immunity. The combination of WT T cells and IL-27
      signal-defective DCs may have therapeutic potential against tumors.

PMID- 19089916
TI  - Telomere length, oxidative damage, antioxidants and breast cancer risk.
AB  - Telomeres play a critical role in maintaining the integrity and stability of the
      genome, and are susceptible to oxidative damage after telomere shortening to a
      critical length. In the present study, we explored the role of white blood cell
      DNA telomere length on breast cancer risk, and examined whether urinary 15-F(2)
      isoprostanes (15-F(2t)-IsoP) and 8-oxo-7,8-dihydrodeoxyguanosine (8-oxodG) or
      dietary antioxidant intake modified the relationship between telomere length and
      breast cancer risk. A population-based case-control study-the Long Island Breast
      Cancer Study Project-was conducted among 1,067 cases and 1,110 controls. Telomere
      length was assessed by quantitative PCR. Overall, the mean levels of telomere
      length (T/S ratio), 15-F(2t)-IsoP and 8-oxodG were not significantly different
      between cases and controls. Among premenopausal women only, carrying shorter
      telomeres (Q3 and Q4), as compared with the longest (Q1), was associated with
      significantly increased breast cancer risk. Age-adjusted OR and 95% CI were 1.71
      (1.10-2.67) and 1.61 (1.05-2.45). The 5-F(2t)-IsoP and 8-oxodG biomarkers did not
      modify the telomere-breast cancer association. A moderate increase in breast
      cancer risk was observed among women with the shortest telomeres (Q4) and lower
      dietary and supplemental intake of beta-carotene, vitamin C or E intake [OR (95%
      CI) = 1.48 (1.08-2.03), 1.39 (1.01-1.92) and 1.57 (1.14-2.18), respectively],
      although the trend test exhibited statistical significance only within the lower
      vitamin E intake subgroup (p(trend) = 0.01). These results provided the strongest
      evidence to date that breast cancer risk may be affected by telomere length among
      premenopausal women or women with low dietary intake of antioxidants or
      antioxidant supplements.

PMID- 19089918
TI  - Serum YKL-40 and bone marrow angiogenesis in multiple myeloma.

PMID- 19089919
TI  - Mechanism of metabolic activation and DNA adduct formation by the human
      carcinogen diethylstilbestrol: the defining link to natural estrogens.
AB  - Diethylstilbestrol (DES) is a human carcinogen, based on sufficient
      epidemiological evidence. DES is mainly metabolized to its catechol, 3'
      hydroxyDES (3'-OH-DES), which can further oxidize to DES-3',4'-quinone (DES-3',4'
      Q). Similarly to estradiol-3,4-quinone, the reaction of DES-3',4'-Q with DNA
      would form the depurinating 3'-OH-DES-6'-N3Ade and 3'-OH-DES-6'-N7Gua adducts. To
      prove this hypothesis, synthesis of DES-3',4'-Q by oxidation of 3'-OH-DES with
      Ag(2)O was tried; this failed due to instantaneous formation of a spiro-quinone.
      Oxidation of 3'-OH-DES by lactoperoxidase or tyrosinase in the presence of DNA
      led to the formation of 3'-OH-DES-6'-N3Ade and 3'-OH-DES-6'-N7Gua adducts. These
      adducts were tentatively identified by LC-MS/MS as 3'-OH-DES-6'-N3Ade, m/z = 418
      [M+H](+), and 3'-OH-DES-6'-N7Gua, m/z = 434 [M+H](+). Demonstration of their
      structures derived from their oxidation by MnO(2) to the DES quinone adducts and
      subsequent tautomerization to the dienestrol (DIES) catechol adducts, which are
      identical to the standard 3'-OH-DIES-6'-N3Ade, m/z = 416 [M+H](+), and 3'-OH-DIES
      6'-N7Gua, m/z = 432 [M+H](+), adducts. The reaction of DIES-3',4'-Q or
      lactoperoxidase-activated 3'-OH-DIES with DNA did not produce any depurinating
      adducts, due to the dienic chain being perpendicular to the phenyl planes, which
      impedes the intercalation of DIES into the DNA. Enzymic oxidation of 3'-OH-DES
      suggests that the catechol of DES intercalates into DNA and is then oxidized to
      its quinone to yield N3Ade and N7Gua adducts. These results suggest that the
      common denominator of tumor initiation by the synthetic estrogen DES and the
      natural estrogen estradiol is formation of their catechol quinones, which react
      with DNA to afford the depurinating N3Ade and N7Gua adducts.

PMID- 19089920
TI  - Diminished IFN-gamma and IL-10 and elevated Foxp3 mRNA expression in the cervix
      are associated with CIN 2 or 3.
AB  - Cervical mucosal expression of cytokines involved in mediating cellular immunity
      is believed to influence the persistence of human papillomavirus (HPV) infection,
      a necessary prerequisite for the development of cervical intraepithelial
      neoplasia (CIN). Additionally, regulatory T (Treg) cells are increasingly
      understood to be important modulators of cellular immunity. Using quantitative RT
      PCR, we measured, in cross-sectional design, the cervical mRNA expression of IFN
      gamma, IL-10, and IL-12, as well as the Treg transcription factor Forkhead box P3
      (Foxp3), in a cohort of young women representing CIN 1, 2, and 3, as well as
      benign histology. Higher levels of IFN-gamma and IL-10 were significantly (p <or=
      0.05) associated with decreased odds of having high-grade cervical disease (CIN 2
      or 3) in multivariate logistic regression models. In contrast, higher levels of
      mucosal Foxp3 expression were associated with increased odds of having CIN 2 or 3
      (p = 0.004). In a multivariate model including cervical infection with HPV16
      and/or another high-risk HPV type, Foxp3 remained higher in the CIN 2/3 group,
      but the difference was notably less significant (p = 0.05). These findings
      support a model in which diminished cellular immunity in the cervical mucosa and
      mucosal enrichment of Treg cells both contribute to the development of high-grade
      lesions.

PMID- 19089921
TI  - Downregulation of vascular endothelial growth factor and induction of tumor
      dormancy by 15-lipoxygenase-2 in prostate cancer.
AB  - The enzyme 15-lipoxygenase-2 (15-LOX-2) utilizes arachidonic acid, a
      polyunsaturated fatty acid, to synthesize 15(S)-hydroxyeicosatetraenoic acid.
      Abundantly expressed in normal prostate epithelium but frequently suppressed in
      the cancerous tissues, 15-LOX-2 has been suggested as a functional suppressor of
      prostate cancer, but the mechanism(s) involved remains unknown. To study the
      functional role of 15-LOX-2 in prostate cancer, we expressed 15-LOX-2 as a fusion
      protein with GFP in DU145 and PC-3 cells and found that 15-LOX-2 increased cell
      cycle arrest at G0/G1 phase. When injected into athymic nu/nu mice, prostate
      cancer cells with 15-LOX-2 expression could still form palpable tumors without
      significant changes in tumorigenicity. But, the tumors with 15-LOX-2 expression
      grew significantly slower than those derived from vector controls and were kept
      dormant for a long period of time. Histological evaluation revealed an increase
      in cell death in tumors derived from prostate cancer cells with 15-LOX-2
      expression, while in vitro cell culture conditions, no such increase in apoptosis
      was observed. Further studies found that the expression of vascular endothelial
      growth factor A (VEGF-A) was significantly reduced in prostate cancer cells with
      15-LOX-2 expression restored. Our studies suggest that 15-LOX-2 suppresses VEGF
      gene expression and sustains tumor dormancy in prostate cancer. Loss of 15-LOX-2
      functionalities, therefore, represents a key step for prostate cancer cells to
      exit from dormancy and embark on malignant progression in vivo.

PMID- 19089923
TI  - Integrating tumor-initiating cells into the paradigm for melanoma targeted
      therapy.
AB  - There is growing evidence to suggest that not all cancer cells have similar
      levels of malignant potential and that tumor progression may be driven by
      specialized sub-sets of "tumor initiating" cells. It is likely that as tumor
      initiating cells have lower proliferation rates and enhanced survival mechanisms
      they may also drive drug resistance. Melanoma is known to be an exceptionally
      therapy resistant tumor, with no treatment yet identified to alter the natural
      progression of the disseminated disease. In the current review, we discuss
      evidence for the existence of melanoma initiating cells and described possible
      therapeutic strategies to eradicate this population via the targeting of specific
      cell-surface markers or through the disruption of the interaction of the melanoma
      initiating cells with their local microenvironment. It is hoped that the
      targeting of melanoma initiating cells may be one approach to overcome the
      incredible therapy resistance of this tumor.

PMID- 19089924
TI  - Autoimmunity and lymphomagenesis.
AB  - For more than 50 years, links between autoimmunity and lymphomas have been
      described based on human and animal studies. Over the last 3 decades, many
      studies have addressed specific hypotheses about these associations using
      population level data. This has been accomplished by assessing previous
      autoimmune history in case-control studies of patients with lymphoma (mainly non
      Hodgkin lymphoma) and myeloma, and by following cohorts of patients with various
      autoimmune diseases for subsequent development of lymphoma and multiple myeloma.
      In this article, we review our recently published series of association studies
      based on data from Scandinavia and from US Veterans and other relevant findings.
      We also discuss what these associations have revealed about the mechanisms and
      pathways underlying both autoimmunity and lymphoma. Finally, we discuss the
      future directions involving a combination of population and molecular studies
      that are needed to better define underlying biological mechanisms.

PMID- 19089922
TI  - Isoflavone consumption and subsequent risk of hepatocellular carcinoma in a
      population-based prospective cohort of Japanese men and women.
AB  - The incidence of hepatocellular carcinoma (HCC) is much higher in men than in
      women. Several experiment and epidemiological studies have suggested that
      estrogen might play an inhibitory role in the development of HCC. Because
      isoflavones have a similar structure as 17beta-estradiol and appear to have an
      anti-estrogenic effect in women and estrogenic effect in men, we hypothesized
      that the effect of isoflavones on HCC differs by sex. We investigated the
      association between isoflavones (genistein and daidzein) and soy products and HCC
      in Japan in a population-based prospective study in 19,998 Japanese (7,215 men
      and 12,783 women) aged 40-69 years. During 11.8 years of follow-up, 101 subjects
      (69 men and 32 women) were newly diagnosed with HCC. Case patients were grouped
      according to consumption of isoflavones and soy products and stratified by
      hepatitis virus infection. Hazard ratios (HRs) and 95% confidence intervals (CIs)
      for HCC were calculated by Cox proportional-hazards modeling. In women, genistein
      and daidzein were dose-dependently associated with an increased risk of HCC, with
      multivariable HRs for the highest versus lowest tertile of 3.19 (95%CI = 1.13
      9.00, p(trend) = 0.03) and 3.90 (95% CI = 1.30-11.69, p(trend) = 0.01),
      respectively. No association between isoflavones and HCC was observed in men.
      These results persisted when analysis was restricted to subjects positive for
      either or both hepatitis C and B virus. In conclusion, isoflavone consumption may
      be associated with an increased risk of HCC in women. Women with hepatitis virus
      infection may be advised to abstain from isoflavone consumption. Further studies
      are warranted to confirm these findings.

PMID- 19089925
TI  - Genetic variation in SIPA1 in relation to breast cancer risk and survival after
      breast cancer diagnosis.
AB  - Genetic variation in SIPA1, signal-induced proliferation-associated gene 1, has
      been proposed to be associated with aggressive breast tumor characteristics
      related to metastasis and worse prognosis in humans and rodents. To test this
      hypothesis, we genotyped 3 single nucleotide polymorphisms (SNP) located at -3092
      (A<G, rs931127), exon 3-135 (C>T, rs3741378), and exon 14 + 14 (C>T, rs746429),
      and examined them in relation to breast cancer risk and overall survival,
      stratified by tumor characteristics in 2 independent case-control studies
      conducted in Poland (1,995 cases, 2,296 controls) and in Britain (2,142 cases,
      2,257 controls). Vital status (n = 396 deaths) was available for 911 Polish and
      1,919 British breast cancer cases with an average follow-up time of 5.5 years.
      Overall, we found no significant associations between genetic variants of SIPA1
      SNPs and breast cancer risk (per allele odds ratios, 95% confidence intervals
      (CI): rs931127-0.99, 0.93-1.06; rs3741378-1.03, 0.94-1.13; and, rs74642-0.98,
      0.92-1.04). In both studies, SIPA1 polymorphisms were not related to overall
      mortality (per allele hazard ratios, 95% CI: 1.02, 0.88-1.17; 0.90, 0.72-1.11;
      1.04, 0.90-1.21, respectively). Our results do not support a relationship between
      SIPA1 polymorphisms and breast cancer risk or subsequent survival.

PMID- 19089926
TI  - Induction of the lysosomal apoptosis pathway by inhibitors of the ubiquitin
      proteasome system.
AB  - The lysosomal apoptosis pathway is a potentially interesting therapeutic target.
      Since apoptosis involving the lysosomal pathway has been described to involve
      cathepsins, we screened a drug library for agents that induce cathepsin-dependent
      apoptosis. Using pharmacological inhibitors and siRNA, we identified 2
      structurally related agents (NSC687852 and NSC638646) that induced cathepsin D
      dependent caspase-cleavage activity in human breast cancer cells. Both agents
      were found to induce the mitochondrial apoptosis pathway. NSC687852 and NSC638646
      were found to inhibit the activity of ubiquitin isopeptidases and to induce the
      accumulation of high-molecular-mass ubiquitins in cells. We show that 3 other
      inhibitors of the proteasome degradation pathway induce lysosomal membrane
      permeabilization (LMP) and that cathepsin-D siRNA inhibits apoptosis induced by
      these agents. We conclude that a screen for cathepsin-dependent apoptosis
      inducing agents resulted in the identification of ubiquitin isopeptidase
      inhibitors and that proteasome inhibitors with different mechanisms of action
      induce LMP and cathepsin D-dependent apoptosis.

PMID- 19089928
TI  - Promoter hypermethylation of the ADAM23 gene in colorectal cancer cell lines and
      cancer tissues.
AB  - Promoter hypermethylation of the ADAM23 gene, which is normally involved in cell
      to-cell and cell-to matrix adhesion, has been reported in pancreatic, breast and
      brain cancer, and recently the role of this gene was examined in gastric cancer.
      In this study, we analyzed ADAM23 expression in colorectal cancer cell lines and
      examined its methylation by methylation-specific PCR (MSP) and bisulfate-modified
      DNA sequencing analysis. Methylated cells were treated with 5-aza-2'
      deoxycytidine to restore the ADAM23 expression. We then examined ADAM23
      methylation status in colorectal cancer tissues and their corresponding normal
      tissues. We found that ADAM23 was aberrantly silenced or expressed at very low
      levels in 28 of the 32 (88%) colorectal cancer cell lines. MSP analysis showed
      that ADAM23 was methylated in 29 of 32 (91%) colorectal cancer cell lines and
      attenuated expression of ADAM23 was found to be related to hypermethylation in
      its promoter region. Moreover, the CpG dinucleotide methylation threshold of 70
      90% was found to be required for complete silencing. In addition, when some cell
      lines without ADAM23 expression were treated with 5-aza-2'-deoxycytidine, ADAM23
      was reexpressed. In colorectal cancer tissues, the promoter region of ADAM23 was
      hypermethylated in 36 of 76 (47%). These results demonstrated that ADAM23 may be
      down-regulated by aberrant promoter hypermethylation during the progression of
      colorectal cancer.

PMID- 19089927
TI  - Children with endemic Burkitt lymphoma are deficient in EBNA1-specific IFN-gamma
      T cell responses.
AB  - Endemic Burkitt lymphoma (eBL) is the most common childhood cancer in equatorial
      Africa and is linked to Epstein-Barr virus (EBV) and Plasmodium falciparum
      coinfections early in life. Epstein-Barr nuclear antigen 1 (EBNA1) is the sole
      viral latent antigen expressed in BL tumors. Loss of EBNA1-specific immune
      surveillance could allow eBL emergence. Therefore, EBNA1-specific T cell
      responses were analyzed by IFN-gamma ELISPOT in Kenyan children with eBL and
      compared to healthy children with divergent malaria exposure. Significantly fewer
      children with eBL, 16% (7/44) had EBNA1-specific IFN-gamma responses in contrast
      to healthy children living in a malaria holoendemic area or in an area with
      sporadic malaria transmission, 67% (40/60) and 72% (43/60) responders,
      respectively (p < 0.003). Children with eBL maintained IgG(1) dominated antibody
      responses to EBNA1 similar to healthy children suggesting a selective loss of IFN
      gamma secreting EBNA1-specific T cells in the presence of intact humoral
      immunity. CD8(+) T cell responses to EBV lytic and latent antigens not expressed
      in the tumors were similarly robust in eBL patients compared to healthy children.
      In addition, CD4(+) T cell responses to a malaria protein, merozoite surface
      protein 1, were present in lymphoma patients. This study demonstrates a selective
      loss of EBNA1-specific T cell responses in children with eBL and suggests a
      potential immunotherapeutic target for this EBV-associated lymphoma.

PMID- 19089929
TI  - Antiplatelet drug response variability and the role of platelet function testing:
      a practical guide for interventional cardiologists.
AB  - Antiplatelet therapy is the cornerstone of treatment for patients with acute
      coronary syndrome and is also of particular importance in those who undergo
      percutaneous coronary intervention with stent implantation. Dual antiplatelet
      therapy with aspirin and clopidogrel is associated with improvement in long-term
      clinical outcomes in such patients and is presently the antiplatelet therapy of
      choice for secondary prevention of thrombotic events. However, a significant
      number of patients experience recurrent events despite antiplatelet therapy.
      Although poor patient compliance can account for some of these events,
      particularly in those patients who receive a drug-eluting stent, increasing
      evidence indicates that there is variability in response to antiplatelet therapy
      and patients who have higher levels of platelet reactivity are at increased risk
      for recurrent ischemic events. However, the lack of a consistent definition of
      inadequate platelet response, as well as the lack of a standardized measurement
      technique, has made it difficult to define how to treat these patients. To
      translate findings associated with variability in platelet response into improved
      patient care, it is necessary to gain a better understanding of what variable
      platelet response is, how it is measured, who it should be measured in, and what
      its clinical relevance is. The objective of this review is to evaluate the data
      regarding interindividual response variability to antiplatelet therapy with the
      aim of providing practical considerations and where possible, recommendations,
      regarding this topic for interventional cardiologists.

PMID- 19089930
TI  - Multicenter international registry of unprotected left main coronary artery
      percutaneous coronary intervention with drug-eluting stents in patients with
      myocardial infarction.
AB  - BACKGROUND: Patients who present with myocardial infarction (MI) and unprotected
      left main coronary artery (ULMCA) disease represent an extremely high-risk subset
      of patients. ULMCA percutaneous coronary intervention (PCI) with drug-eluting
      stents (DES) in MI patients has not been extensively studied. METHODS: In this
      retrospective multicenter international registry, we evaluated the clinical
      outcomes of 62 consecutive patients with MI who underwent ULMCA PCI with DES (23
      ST-elevation MI [STEMI] and 39 non-ST-elevation MI [NSTEMI]) from 2002 to 2006.
      RESULTS: The mean age was 70 +/- 12 years. Cardiogenic shock was present in 24%.
      The mean EuroSCORE was 10 +/- 8. Angiographic success was achieved in all
      patients. Overall in-hospital major adverse cardiac event (MACE) rate was 10%,
      mortality was 8%, all due to cardiac deaths from cardiogenic shock, and one
      patient suffered a periprocedural MI. At 586 +/- 431 days, 18 patients (29%)
      experienced MACE, 12 patients (19%) died (the mortality rate was 47% in patients
      with cardiogenic shock), and target vessel revascularization was performed in
      four patients, all of whom had distal bifurcation involvement (two patients
      underwent repeat PCI and two patients underwent bypass surgery). There was no
      additional MI. Two patients had probable stent thrombosis and one had possible
      stent thrombosis. Diabetes [hazard ratio (HR) 4.22, 95% confidence interval (CI)
      (1.07-17.36), P = 0.04), left ventricular ejection fraction [HR 0.94, 95% CI
      (0.90-0.98), P = 0.005), and intubation [HR 7.00, 95% CI (1.62-30.21), P = 0.009)
      were significantly associated with increased mortality. CONCLUSIONS: Patients
      with MI and ULMCA disease represent a very high-risk subgroup of patients who are
      critically ill. PCI with DES appears to be technically feasible, associated with
      acceptable long-term outcomes, and a reasonable alternative to surgical
      revascularization for MI patients with ULMCA disease. Randomized trials are
      needed to determine the ideal revascularization strategy for these patients.

PMID- 19089931
TI  - Percutaneous revascularization of the "unprotected" left main during acute
      myocardial infarction: "Dare to struggle! Dare to win!".

PMID- 19089932
TI  - Early and long-term results of percutaneous coronary intervention for unprotected
      left main trifurcation disease.
AB  - OBJECTIVES: We aimed to conduct a retrospective cohort study focusing on our 5
      year experience in the percutaneous treatment of unprotected left main (ULM)
      trifurcation disease. BACKGROUND: Percutaneous treatment of ULM trifurcation
      remains a challenging and rare procedure for most interventional cardiologists.
      Moreover, data on long-term outcomes are lacking. METHODS: We retrieved all
      patients with ULM trifurcation disease treated percutaneously at our Institution
      since 2002, and adjudicated baseline, procedural, and outcome data. The primary
      end point was the long-term rate of major adverse cardiovascular events (MACE,
      i.e., cardiac death, myocardial infarction, bypass surgery, or target vessel
      revascularization). RESULTS: A total of 27 patients underwent percutaneous
      coronary intervention with stent implantation for ULM trifurcation disease, with
      14 (52%) cases of true trifurcations, i.e., with concomitant significant stenoses
      of the distal ULM/ostial left anterior descending plus ostial ramus intermedius
      and ostial circumflex. Bare-metal stents were implanted in 8 (29%) patients and
      drug-eluting stents (DES) in 26 (96%), with a main branch stent only strategy in
      11 (40%), T stenting in 9 (33%), and V stenting in 6 (27%). Procedural and
      clinical success occurred in 26 (96%), with one postprocedural death.
      Angiographic follow-up was obtained in 22 patients (81%), and clinical follow-up
      was completed in all subjects after a median of 28 +/- 17 months, showing overall
      MACE in 9 (33%), with cardiac death in 4 (15%), myocardial infarction in 1 (4%),
      coronary artery bypass grafting (CABG) in 4 (15%), and percutaneous target vessel
      revascularization in 5 (19%). Definite stent thrombosis was adjudicated in 1 (3%)
      patient. Treatment of a true trifurcation lesion and recurrence of angina during
      follow-up were significantly associated with an increased risk of MACE (P = 0.029
      and P = 0.050, respectively). CONCLUSIONS: Percutaneous treatment of ULM
      trifurcation disease is feasible, associated with favorable mid-term results, and
      may be considered given its low invasiveness in patients at high surgical risk or
      with multiple comorbidities.

PMID- 19089933
TI  - Trifurcation left main coronary artery percutaneous revascularization--pushing
      catheters and envelopes.

PMID- 19089934
TI  - Analysis of left main coronary artery bifurcation lesions treated with biolimus
      eluting DEVAX AXXESS plus nitinol self-expanding stent: intravascular ultrasound
      results of the AXXENT trial.
AB  - OBJECTIVE: To assess the efficacy of the AXXESS stent on the treatment of left
      main coronary artery (LMCA) bifurcation lesions using IVUS. BACKGROUND: The
      treatment of LMCA bifurcation lesions remains challenging even with the use of
      drug-eluting stents. The AXXESS system is a biolimus A9-eluting self-expanding
      stent, dedicated to the treatment of bifurcation lesions. METHODS: Data were
      obtained from the AXXENT trial, a prospective, single-arm, multicenter study
      designed to evaluate the efficacy of the AXXESS stent on the treatment of LMCA
      bifurcation lesions. IVUS was available in 26 cases at 6-months follow-up.
      Volumetric and cross-sectional analyses within the AXXESS stent, and cross
      sectional analyses at the ostia of left anterior descending (LAD) and left
      circumflex coronary arteries (LCX) were performed. RESULTS: Within the AXXESS
      stent, percent neointimal volume obstruction was (3.0 +/- 4.1)% with a minimal
      lumen area of 10.3 +/- 2.6 mm(2). AXXESS stent volume showed an 12.4% increase at
      follow-up compared with postprocedure (P = 0.04). Lumen area was significantly
      smaller in the LCX ostium compared with the LAD ostium at follow-up (3.6 +/- 1.3
      mm(2) vs. 5.5 +/- 2.0 mm(2), P = 0.0112). There was greater neointimal formation
      in the LCX ostium compared with the LAD ostium (1.37 +/- 1.20 mm(2) vs. 0.30 +/-
      0.36 mm(2), P = 0.0003). CONCLUSIONS: The AXXESS stent in the LMCA showed
      enlargement through 6-months follow-up and significant neointimal suppression.
      Greater neointimal formation and relatively inadequate stent expansion may
      contribute to luminal narrowing in the LCX ostium.

PMID- 19089935
TI  - Treating the left main bifurcation lesion: the "three stent solution".

PMID- 19089936
TI  - Percutaneous coronary intervention in anticoagulated patients via radial artery
      access.
AB  - OBJECTIVES: To assess safety and feasibility of using radial artery access for
      percutaneous coronary intervention (PCI) in patients on oral anticoagulation
      without interrupting therapy. BACKGROUND: The radial artery approach for PCI is
      intuitively attractive for patients receiving chronic oral anticoagulation with
      vitamin K antagonists (VKAs) but little data exist concerning feasibility or
      safety of this approach in this population. The main advantage of this strategy
      would be to avoid bridging therapy with heparin that increases risk of thrombotic
      and bleeding events. METHODS: In this prospective observational study, 50
      consecutive patients referred for coronary angiography underwent PCI without
      interrupting oral anticoagulant therapy. The main outcome measures were bleeding
      and thrombotic complications. RESULTS: The indications for permanent oral
      anticoagulation were as follows: atrial fibrillation in 62%, mechanical
      prosthesis in 24%, and venous thromboembolism in 14%. Seventy-two percent were
      elective cases and 28% presented with acute coronary syndromes. PCI was performed
      with an INR range of 1.4-3.4 with mean of 2.2 +/- 0.6. Seventy-six percent of the
      patients were on dual antiplatelet therapy before the procedure. No thrombotic
      events or excess bleeding were observed at 1 month. Only one patient had a minor
      hemorrhage 8 days after procedure. CONCLUSIONS: This series suggests that for
      patients treated with VKAs, the use of radial artery access is feasible and safe
      for PCI on dual antiplatelet therapy without interrupting oral anticoagulant
      treatment.

PMID- 19089937
TI  - Hazard--the anticoagulation bridge or just go transradial.

PMID- 19089938
TI  - PCI versus CABG for multivessel coronary disease in diabetics.
AB  - OBJECTIVES: To explore the clinical performance of a strategy of
      revascularization by percutaneous coronary intervention (PCI) with drug-eluting
      stent (DES) in diabetic patients with multivessel disease (MVD) compared with
      coronary artery bypass graft (CABG), when it is based on clinical judgment.
      BACKGROUND: Diabetes mellitus (DM) is a major risk factor for poor outcome after
      PCI. However, PCI may result in better outcome if the choice of revascularization
      (PCI versus CABG) is based on the physician decision, rather than randomization.
      Limited experiences have compared revascularization by DES-PCI versus CABG in DM
      patients with MVD. METHODS: From August 2004 to August 2005, 220 consecutive DM
      patients with MVD underwent DES-PCI (93) or CABG (127) at our Institution. The
      type of revascularization was dependent on patient and/or physician choice. Major
      adverse cardiac and cerebrovascular events (MACCE) included death, myocardial
      infarction, repeat coronary revascularization, and stroke. RESULTS: Compared with
      PCI patients, CABG patients had higher prevalence of 3-vessel disease (P <
      0.001), significant LAD involvement (P < 0.001), presence of total occlusions (P
      = 0.04), collateral circulation (P < 0.001). At 2-year follow-up, MACCE were not
      different between CABG group and DES-PCI group (OR 1.2; P = 0.6) and, only when
      the clinical judgment on the revascularization choice was excluded at propensity
      analysis, DES-PCI increased the risk of 24-month MACCE in total population (OR
      1.8; P = 0.04). CONCLUSIONS: For patients with DM and MVD, a clinical judgment
      based revascularization by DES-PCI is not associated with worse 2-year outcome
      compared with CABG.

PMID- 19089939
TI  - CABG versus DES PCI in diabetics with multivessel disease: back to the BARI
      registry.

PMID- 19089940
TI  - Successful percutaneous coronary intervention after implantation of a CoreValve
      percutaneous aortic valve.
AB  - BACKGROUND: The association between aortic valve disease and coronary
      atherosclerosis is common. In the recent era of percutaneous aortic valve
      replacement (PAVR), there is little experience with coronary artery intervention
      after valve implantation. CASE REPORT: To our knowledge, this is the first case
      of successful percutaneous coronary intervention after implantation of a
      CoreValve percutaneous aortic valve. We report a case of a 79-year-old female
      patient who underwent successful coronary artery intervention few months after a
      CoreValve's percutaneous implantation for severe aortic valve stenosis. Verifying
      the position of the used wires (crossing from inside the self expanding frame) is
      of utmost importance before proceeding to coronary intervention. In this case,
      crossing the aortic valve, coronary angiography, and multivessel stenting were
      successfully performed. CONCLUSION: Percutaneous coronary intervention in
      patients with previous CoreValve is feasible and safe.

PMID- 19089941
TI  - All-atom chain-building by optimizing MODELLER energy function using
      conformational space annealing.
AB  - We have investigated the effect of rigorous optimization of the MODELLER energy
      function for possible improvement in protein all-atom chain-building. For this we
      applied the global optimization method called conformational space annealing
      (CSA) to the standard MODELLER procedure to achieve better energy optimization
      than what MODELLER provides. The method, which we call MODELLERCSA, is tested on
      two benchmark sets. The first is the 298 proteins taken from the HOMSTRAD
      multiple alignment set. By simply optimizing the MODELLER energy function, we
      observe significant improvement in side-chain modeling, where MODELLERCSA
      provides about 10.7% (14.5%) improvement for chi(1) (chi(1) + chi(2)) accuracy
      compared to the standard MODELLER modeling. The improvement of backbone accuracy
      by MODELLERCSA is shown to be less prominent, and a similar improvement can be
      achieved by simply generating many standard MODELLER models and selecting lowest
      energy models. However, the level of side-chain modeling accuracy by MODELLERCSA
      could not be matched either by extensive MODELLER strategies, side-chain
      remodeling by SCWRL3, or copying unmutated rotamers. The identical procedure was
      successfully applied to 100 CASP7 template base modeling domains during the
      prediction season in a blind fashion, and the results are included here for
      comparison. From this study, we observe a good correlation between the MODELLER
      energy and the side-chain accuracy. Our findings indicate that, when a good
      alignment between a target protein and its templates is provided, thorough
      optimization of the MODELLER energy function leads to accurate all-atom models.

PMID- 19089942
TI  - The actin-binding domain of cortactin is dynamic and unstructured and affects
      lateral and longitudinal contacts in F-actin.
AB  - Cortactin is an F-actin- and Arp2/3 complex-binding protein, implicated in the
      regulation of cytoskeleton dynamics and cortical actin-assembly. The actin
      binding domain of cortactin consists of a 6.5 tandem repeat of a 37-amino acid
      sequence known as the cortactin repeat (residues 80-325). Using a combination of
      structure prediction, circular dichroism, and cysteine crosslinking, we tested a
      recently published three-dimensional model of the cortactin molecule in which the
      cortactin repeat is folded as a globular helical domain [Zhang et al., 2007, Mol
      Cell 27:197-213]. We show that the cortactin repeat is unstructured in solution.
      Thus, wild type and mutant constructs of the cortactin repeat, containing pairs
      of cysteines at positions 112 and 246, 83 and 112, 83 and 246, and 83 and 306,
      could be readily crosslinked with reagents of varying lengths (0-9.6 A). Using
      yeast actin cysteine mutants, we also show that cortactin inhibits disulfide and
      dibromobimane crosslinking across the lateral and longitudinal interfaces of
      actin subunits in the filament, suggesting a weakening of intersubunits contacts.
      Our results are in disagreement with the proposed model of the cortactin molecule
      and have important implications for our understanding of cortactin regulation of
      cytoskeleton dynamics.

PMID- 19089943
TI  - Functional implications of membrane modification with semenogelins for inhibition
      of sperm motility in humans.
AB  - Semenogelin I and II (Sgs) are the major component of human semen coagulum. The
      protein is rapidly cleaved after ejaculation by a prostate-specific antigen,
      resulting in liquefaction of the semen coagulum and the progressive release of
      motile spermatozoa. Sgs inhibit human sperm motility; however, there is currently
      no information on its effect on the sperm membrane. This study investigated the
      role of Sgs on human sperm motility through regulation of membrane potential and
      membrane permeability. Fresh semen samples were obtained from normozoospermic
      volunteers, and studies were conducted using motile cells selected using the swim
      up method. Sgs changed the characteristics of sperm motion from circular to
      straightforward as evaluated by a computer-assisted motility analyzer, and all
      parameters were decreased more than 2.5 mg/mL. The results demonstrate that Sgs
      treatment immediately hyperpolarized the membrane potential of swim-up-selected
      sperm, changed the membrane structure, and time-dependently increased membrane
      permeability, as determined through flow cytometric analysis. The biphasic
      effects of Sgs were time- and dose-dependent and partially reversible. In
      addition, a monoclonal antibody against Sgs showed positive binding to cell
      membrane proteins in fixed cells, observed with confocal fluorescence microscopy.
      These results demonstrate that Sgs modifies the membrane structure, indirectly
      inhibiting motility, and provides suggestions for a therapy for male infertility
      through selection of a functional sperm population using Sgs.

PMID- 19089944
TI  - "How deficient can the IVC rim be?".

PMID- 19089945
TI  - High pressure reveals structural determinants for globin hexacoordination:
      neuroglobin and myoglobin cases.
AB  - The influence of pressure on the equilibrium between five-(5c) and six
      coordination (6c) forms in neuroglobin (Ngb) and myoglobin (Mb) has been examined
      by means of molecular dynamics (MD) simulations at normal and high pressure. The
      results show that the main effect of high pressure is to reduce the protein
      mobility without altering the structure in a significant manner. Moreover, our
      data suggest that the equilibrium between 5c and 6c states in globins is largely
      controlled by the structure and dynamics of the C-D region. Finally, in agreement
      with the available experimental data, the free energy profiles obtained from
      steered MD for both proteins indicate that high pressure enhances
      hexacoordination. In Ngb, the shift in equilibrium is mainly related to an
      increase in the 6c-->5c transition barrier, whereas in Mb such a shift is
      primarily due to a destabilization of the 5c state.

PMID- 19089946
TI  - Multiple stent fractures at the site of coronary artery bypass insertion.
AB  - Drug eluting stents have led to a substantial reduction of in-stent restenosis.
      Stent fracture (SF) is an important cause for the cases of restenosis which still
      occur. Sites of increased vessel movement, long stents, and overlapping stents
      have been observed to be more prone to fracture. We report the case of a patient
      with multiple drug eluting SFs at the site of coronary artery bypass insertion.
      The decision to implant stents at the site of bypass insertion should be made
      carefully. SF should be considered when gaps between previously implanted stents
      are observed.

PMID- 19089948
TI  - Coronary stent fracture: the hidden truth of a problem more common than stent
      thrombosis.

PMID- 19089947
TI  - Natural history of the E1-like superfamily: implication for adenylation, sulfur
      transfer, and ubiquitin conjugation.
AB  - The E1-like superfamily is central to ubiquitin (Ub) conjugation, biosynthesis of
      cysteine, thiamine, and MoCo, and several secondary metabolites. Yet, its
      functional diversity and evolutionary history is not well understood. We develop
      a natural classification of this superfamily and use it to decipher the major
      adaptive trends occurring in the evolution of the E1-like superfamily. Within the
      Rossmann fold, E1-like proteins are closest to NAD(P)/FAD-dependent
      dehydrogenases and S-AdoMet-dependent methyltransferases. Hence, their
      phosphotransfer activity is an independent catalytic "invention" with respect to
      such activities seen in other Rossmannoid folds. Sequence and structure analysis
      reveals a striking diversity of residues and structures involved in adenylation,
      sulfotransfer, and substrate binding between different E1-like families, allowing
      us to predict previously uncharacterized functional adaptations. E1-like proteins
      are fused to several previously undetected domains, such as a predicted sulfur
      transfer domain containing a novel superfamily of the TATA-binding protein fold,
      different types of catalytic domains, a novel winged helix-turn-helix domain and
      potential adaptor domains related to Ub conjugation. On the basis of these
      fusions, we develop a generalized model for the linking of E1 catalyzed
      adenylation/thiolation with further downstream reactions. This is likely to
      involve a dynamic interplay between the E1 active sites and diverse fused C
      terminal domains. We also predict participation of E1-like domains in previously
      uncharacterized bacterial secondary metabolism pathways, new cysteine
      biosynthesis systems, such as those associated with archaeal O-phosphoseryl tRNA,
      metal-sulfur cluster assembly (e.g., in nitrogen fixation) and Ub-conjugation.
      Evolutionary reconstructions suggest that the last universal common ancestor
      contained a single E1-like domain possessing both phosphotransfer and thiolating
      activities and participating in multiple sulfotransfer reactions. The E1-like
      superfamily subsequently expanded to include 26 families clustering into three
      major radiations. These are broadly involved in Ub activation, cofactor and
      cysteine biosynthesis, and biosynthesis of secondary metabolites. In light of
      this, we present evidence that in eukaryotes other E1-like enzymes such as Urm1
      were independently recruited for Ubl conjugation, probably functioning without
      conventional E2-like enzymes.

PMID- 19089949
TI  - An intact SAM-dependent methyltransferase fold is encoded by the human endothelin
      converting enzyme-2 gene.

PMID- 19089950
TI  - C-terminal tail derived from the neighboring subunit is critical for the activity
      of Thermoplasma acidophilum D-aldohexose dehydrogenase.
AB  - The D-aldohexose dehydrogenase from the thermoacidophilic archaeon Thermoplasma
      acidophilum (AldT) is a homotetrameric enzyme that catalyzes the oxidation of
      several D-aldohexoses, especially D-mannose. AldT comprises a unique C-terminal
      tail motif (residues 247-255) that shuts the active-site pocket of the
      neighboring subunit. The functional role of the C-terminal tail of AldT has been
      investigated using mutational and crystallographic analyses. A total of four C
      terminal deletion mutants (Delta254, Delta253, Delta252, and Delta249) and two
      site-specific mutants (Y86G and P254G) were expressed by Escherichia coli and
      purified. Enzymatic characterization of these mutants revealed that the C
      terminal tail is a requisite and that the interaction between Tyr86 and Pro254 is
      critical for enzyme activity. The crystal structure of the Delta249 mutant was
      also determined. The structure showed that the active-site loops undergo a
      significant conformational change, which leads to the structural deformation of
      the substrate-binding pocket.

PMID- 19089951
TI  - Effect of pressure on helix-coil transition of an alanine-based peptide: an FTIR
      study.
AB  - Effects of pressure and temperature on the helix-coil transition of an alanine
      based peptide (Ac- AA(AAKAA)(3)AAY-NH(2)) have been investigated using CD and
      FTIR spectroscopy. From the correlation between CD and FTIR data, we showed that
      the change in infrared intensity of the amide I' band at 1633 cm(-1) is almost
      identical to the change in the helical content calculated from the CD result.
      Thus, we monitored the amide I' band intensity at 1633 cm(-1) to determine the
      helical content at high pressures. We determined free energy, enthalpy, and
      volume changes upon unfolding of the alpha-helix. The obtained volume change
      (0.98 +/- 0.04 cm(3) mol(-1) res(-1) at 25.4 degrees C) is not consistent with a
      recent molecular dynamics simulation study by Pascheck et al. who used
      temperature-pressure replica exchange methods (Paschek, Gnanakaran, and Garcia,
      Proc Natl Acad Sci USA 2005;102:6765-6770). They reported a small negative volume
      change upon unfolding of the alpha-helix, indicating that pressure induced the
      peptide to unfold. Pressure dependence of the band-width of the amide I' band
      also supported the present experimental results in which pressure induces the
      peptide to fold, which is also apparently inconsistent with the pressure-induced
      protein unfolding that is generally observed. We propose a hypothesis to unravel
      the paradox of pressure-induced peptide folding and protein unfolding.

PMID- 19089952
TI  - G protein inactive and active forms investigated by simulation methods.
AB  - Molecular dynamics and computational alanine scanning techniques have been used
      to investigate G proteins in their inactive state (the Galpha(i1)beta(1)gamma(2)
      heterotrimer) as well as in their empty and monomeric active states (Galpha(i1)
      subunit). We find that: (i) the residue Q204 of Galpha(i1) plays a key role for
      binding Gbeta(1)gamma(2) and is classified among the most relevant in the
      interaction with a key cellular partner, the so-called regulator of G protein
      signaling protein. The mutation of this residue to L, which is observed in a
      variety of diseases, provides still fair stability to the inactive state because
      of the formation of van der Waals interactions. (ii) The empty state turns out to
      adopt some structural features of the active one, including a previously
      unrecognized rearrangement of a key residue (K46). (iii) The so-called Switch IV
      region increases its mobility on passing from the empty to the active state, and,
      even more, to the inactive state. Such change in mobility could be important for
      its several structural and functional roles. (iv) A large scale motion of the
      helical domain in the inactive state might be important for GDP release upon
      activation by GPCR, consistently with experimental data.

PMID- 19089953
TI  - Spontaneous beta-helical fold in prion protein: the case of PrP(82-146).
AB  - The presence of amyloid is a hallmark of Gerstmann-Straussler-Scheinker (GSS)
      disease, which is a prion disease caused by germ line mutations in the PRNP gene.
      The major component of amyloid is a fragment spanning residues from 81-82 to 144
      153, part of the minimal sequence thought to play a crucial role in the
      conversion reaction and to sustain prion replication. We present here a molecular
      dynamics study on the 82-146 peptide from the human prion protein. The aim is to
      identify its aggregation-prone folds. The 82-146 prion sequence corresponds to a
      naturally occurring prion peptide able to form fibrils rich in parallel beta
      sheets. A spontaneous right-handed beta-helical arrangement with 13 residues per
      turn can be observed in the 103-135 segment of the 82-146 peptide. The observed
      fold is in accordance with the evidence of a parallel beta-sheet organization in
      amyloid and with experiments on 82-146 discussed in the literature. To elucidate
      the conformational properties that trigger this peptide's aggregation propensity,
      the conformational behavior of peptides of different length (106-126 and 113-120
      prion segments) was also investigated. Simulation analysis has led to some
      interesting considerations on sequence specific flexibility and the effects of
      growth. Comparing peptides of different length allows the localization of the
      origin of the beta-helix conformational propensity in the 106-126 segment, though
      longer sequences appear necessary for a clear beta-helical arrangement.
      Structural features of the observed 82-146 beta-helical fold are compatible with
      the "dock and lock" mechanism proposed to interpret peptide aggregation kinetics.

PMID- 19089954
TI  - Thermodynamics and dynamics of amyloid peptide oligomerization are sequence
      dependent.
AB  - Aggregation of the full-length amyloid-beta (Abeta) and beta2-microglobulin
      (beta2m) proteins is associated with Alzheimer's disease and dialysis-related
      amyloidosis, respectively. This assembly process is not restricted to full-length
      proteins, however, many short peptides also assemble into amyloid fibrils in
      vitro. Remarkably, the kinetics of amyloid-fibril formation of all these
      molecules is generally described by a nucleation-polymerization process
      characterized by a lag phase associated with the formation of a nucleus, after
      which fibril elongation occurs rapidly. In this study, we report using long
      molecular dynamics simulations with the OPEP coarse-grained force field, the
      thermodynamics and dynamics of the octamerization for two amyloid 7-residue
      peptides: the beta2m83-89 NHVTLSQ and Abeta16-22 KLVFFAE fragments. Based on
      multiple trajectories run at 310 K, totaling 2.2 mus (beta2m83-89) and 4.8 mus
      (Abeta16-22) and starting from random configurations and orientations of the
      chains, we find that the two peptides not only share common but also very
      different aggregation properties. Notably, an increase in the hydrophobic
      character of the peptide, as observed in Abeta16-22 with respect to beta2m83-89
      impacts the thermodynamics by reducing the population of bilayer beta-sheet
      assemblies. Higher hydrophobicity is also found to slow down the dynamics of beta
      sheet formation by enhancing the averaged lifetime of all configuration types
      (CT) and by reducing the complexity of the CT transition probability matrix.
      Proteins 2009. (c) 2008 Wiley-Liss, Inc.

PMID- 19089956
TI  - Investigating the binding of beta-1,4-galactan to Bacillus licheniformis beta-1,4
      galactanase by crystallography and computational modeling.
AB  - Microbial beta-1,4-galactanases are glycoside hydrolases belonging to family 53,
      which degrade galactan and arabinogalactan side chains in the hairy regions of
      pectin, a major plant cell wall component. They belong to the larger clan GH-A of
      glycoside hydrolases, which cover many different poly- and oligosaccharidase
      specificities. Crystallographic complexes of Bacillus licheniformis beta-1,4
      galactanase and its inactive nucleophile mutant have been obtained with methyl
      beta(1-->4)-galactotetraoside, providing, for the first time, information on
      substrate binding to the aglycone side of the beta-1,4-galactanase substrate
      binding groove. Using the experimentally determined subsites as a starting point,
      a beta(1-->4)-galactononaose was built into the structure and subjected to
      molecular dynamics simulations giving further insight into the residues involved
      in the binding of the polysaccharide from subsite -4 to +5. In particular, this
      analysis newly identified a conserved beta-turn, which contributes to subsites -2
      to +3. This beta-turn is unique to family 53 beta-1,4-galactanases among all clan
      GH-A families that have been structurally characterized and thus might be a
      structural signature for endo-beta-1,4-galactanase specificity.

PMID- 19089955
TI  - Mechanism of formation of the C-terminal beta-hairpin of the B3 domain of the
      immunoglobulin binding protein G from Streptococcus. I. Importance of hydrophobic
      interactions in stabilization of beta-hairpin structure.
AB  - We previously studied a 16-amino acid-residue fragment of the C-terminal beta
      hairpin of the B3 domain (residues 46-61), [IG(46-61)] of the immunoglobulin
      binding protein G from Streptoccocus, and found that hydrophobic interactions and
      the turn region play an important role in stabilizing the structure. Based on
      these results, we carried out systematic structural studies of peptides derived
      from the sequence of IG (46-61) by systematically shortening the peptide by one
      residue at a time from both the C- and the N-terminus. To determine the structure
      and stability of two resulting 12- and 14-amino acid-residue peptides, IG(48-59)
      and IG(47-60), respectively, we carried out circular dichroism, NMR, and
      calorimetric studies of these peptides in pure water. Our results show that IG(48
      59) possesses organized three-dimensional structure stabilized by hydrophobic
      interactions (Tyr50-Phe57 and Trp48-Val59) at T = 283 and 305 K. At T = 313 K,
      the structure breaks down because of increased chain entropy, but the turn region
      is preserved in the same position observed for the structure of the whole
      protein. The breakdown of structure occurs near the melting temperature of this
      peptide (T(m) = 310 K) measured by differential scanning calorimetry (DSC). The
      melting temperature of IG(47-60) determined by DSC is T(m) = 330 K and its
      structure is similar to that of the native beta-hairpin at all (lower)
      temperatures examined (283-313 K). Both of these truncated sequences are
      conserved in all known amino acid sequences of the B domains of the
      immunoglobulin binding protein G from bacteria. Thus, this study contributes to
      an understanding of the mechanism of folding of this whole family of proteins,
      and provides information about the mechanism of formation and stabilization of a
      beta-hairpin structural element.

PMID- 19089957
TI  - Mechanical unfolding pathway and origin of mechanical stability of proteins of
      ubiquitin family: an investigation by steered molecular dynamics simulation.
AB  - Like the muscle protein Titin, proteins of the ubiquitin family exhibit a
      parallel strand arrangement, but otherwise having a distinctly different fold and
      not involved in an obvious load-bearing function, exhibit high resistance to
      mechanical unfolding. We have applied all-atom molecular dynamics simulation
      technique in implicit solvent to present a deep insight into the force-induced
      unfolding pathway of three proteins--ubiquitin, NEDD8, and SUMO-2--all having
      almost similar structural features. Two intermediates evolve in the unfolding
      pathway of each of the three proteins. The first intermediate, which has already
      been identified in case of ubiquitin by earlier simulation results, is similar
      for ubiquitin and NEDD8, but different in SUMO-2. We have found a new
      intermediate with beta3-beta4 hairpin and some residual alpha-helical character;
      and this intermediate is common for all the three proteins. Thus, proteins of the
      ubiquitin family pass through a well-defined conformation in their force-induced
      unfolding pathway. Reason behind the higher mechanical stability of the proteins
      with parallel strand structures like Titin has also been identified.

PMID- 19089958
TI  - Crystal structure of Npun_R1517, a putative negative regulator of heterocyst
      differentiation from Nostoc punctiforme PCC 73102.

PMID- 19089959
TI  - Catheter closure of atrial septal defects with deficient inferior vena cava rim
      under transesophageal echo guidance.
AB  - OBJECTIVES: To describe the case selection, imaging considerations, technique,
      and results of catheter closure of atrial septal defects (ASD) with deficient
      inferior vena cava (IVC) rim. BACKGROUND: Transcatheter closure with Amplatzer
      septal occluder (ASO) has become standard treatment for most secundum ASDs.
      Defects with deficient IVC rim continue to be challenging to image and close in
      the catheterization laboratory. METHODS: Records of 12 patients with deficient
      IVC rim (<5 mm), who underwent catheter closure (April 2007 to June 2008) were
      reviewed. General anesthesia and transesophageal echo (TEE) guidance was used in
      all. The IVC rim was imaged at 70 degrees-90 degrees with retroflexion of the TEE
      probe, in addition to the conventional views. Devices 1-4 mm > maximal ASD size
      were selected. Deployment was accomplished either from the left atrium, left
      upper or from the right pulmonary veins. RESULTS: The median age was 5.5 (2.5-27)
      years and median weight was 19.5 (9-65) kg. The defects measured 16-32 mm and 18
      36 mm septal occluders were used. The median fluoroscopic time was 13.1 (4.2
      32.7) min. Initial device selection was revised in four patients. Two patients
      had residual flows at IVC margin. The device embolized to right ventricular
      outflow tract in one patient. This was retrieved, and a larger device was
      deployed. No other complications were observed immediately or on follow-up
      (median 6; range 1-14 months). CONCLUSIONS: Transcatheter closure of ASDs with
      deficient IVC rim is feasible under TEE guidance. The modified retroflexed view
      allows adequate imaging of IVC rim through TEE.

PMID- 19089961
TI  - Strategies in the management of coronary artery disease and transcatheter aortic
      valve implantation.

PMID- 19089962
TI  - Assessment with optical coherence tomography of a new strategy for bifurcational
      lesion treatment: the Tryton Side-Branch Stent.
AB  - The Tryton-Side Branch Stent (Tryton Medical, Inc., Newton, MA, USA) is a
      dedicated stent designed to provide complete carinal coverage of bifurcational
      lesions. After implantation of a 18 mm cobalt chromium Tryton stent from the left
      circumflex into the obtuse marginal branch, recrossing with an everolimus eluting
      Promus stent and final kissing balloon dilatation, optical coherence tomography
      (OCT) (LightLab Imaging Inc., Westford, MA, USA) was performed with a non
      occlusive technique with motorized pullback (3 mm/s) during continuous pump
      injection of iso-osmolar contrast, in both LCx and OM1. OCT imaging showed good
      strut apposition at the level of the carina, with full coverage and no stent
      protrusion at the ostium of the side branch. Few malapposed struts were present
      in the proximal main vessel in the segment of stent superimposition, with a
      maximal separation from to the vessel wall of 160 microm. The implantation of the
      Tryton-Side Branch Stent allowed full coverage of the side branch ostium with
      uniform apposition of the stent struts at the level of the carina assessed by
      OCT.

PMID- 19089963
TI  - The practicality of optical coherent tomography for coronary imaging.

PMID- 19089964
TI  - Coronary stent infections: a case series.
AB  - Stent infection is a rare sequela of coronary stent implantation first reported
      fifteen years ago. Since that time, much has been learned about this dramatic
      disease entity by way of case report and review. Nevertheless, clinical
      experience with regard to the diagnosis and management of coronary artery stent
      infection remains limited. Here, we report 3 cases of coronary stent infections;
      2 with mycotic aneurysms (seen on coronary angiography) that ruptured into an
      adjacent cardiac chamber, and one with purulent pericarditis. The microbiology as
      well as the possible mechanisms and risk factors for these infections are
      discussed.

PMID- 19089965
TI  - Intracoronary stent infection ... Beware the bugs.

PMID- 19089966
TI  - Step-by-step StentBoost-guided small vessel stenting using the self-expandable
      Sparrow stent-in-wire.
AB  - A 56 year-old woman underwent percutaneous coronary intervention for a lesion in
      a small mid-left anterior descending coronary artery (reference vessel diameter
      by quantitative coronary angiography: 2.11 mm) with a novel drug-eluting stent
      specifically designed for small vessels, the CardioMind Sparrow stent delivery
      system. This is a self-expandable sirolimus-eluting nitinol stent directly
      mounted into a 0.014-inch coronary guidewire. The stent has a very thin strut
      thickness (67 micron), limiting its radiopacity. A specific X-ray stent-enhancing
      visualization technique, "StentBoost", allowed clear visualization and
      understanding of the steps needed for an appropriate release and deployment of
      the aforementioned stent.

PMID- 19089967
TI  - Aerosolized iloprost for pulmonary vasoreactivity testing in children with long
      standing pulmonary hypertension related to congenital heart disease.
AB  - BACKGROUND: In congenital heart disease with increased pulmonary blood flow and
      pressure, progressive changes in the vascular structure can lead to irreversible
      pulmonary hypertension (PH). Pulmonary hemodynamic parameters are used to
      determine whether surgical correction is no longer indicated. In this study,
      aerosolized iloprost was used to assess pulmonary vasoreactivity in children with
      long-standing PH related to congenital heart disease. METHODS: Children with long
      standing and severe PH secondary to congenital heart disease were included in
      this study. Various hemodynamic parameters were measured before and after
      iloprost inhalation (0.5 microg/kg), and vascular resistance was determined.
      Responders to the iloprost test were defined as those with a decrease in both
      pulmonary vascular resistance (PVR) and pulmonary-to-systemic vascular resistance
      ratio (R(p)/R(s)) of >10%. RESULTS: Eighteen children aged between 7 months and
      13 years with long-standing and severe PH secondary to congenital heart disease
      were studied. Thirteen children had a positive response, resulting in a mean (+/-
      SD) decrease of PVR from 9.3 +/- 4.6 to 4.6 +/- 2.7 Wood U x m(2) (P < 0.001),
      and a mean decrease of R(p)/R(s) from 0.54 +/- 0.37 to 0.24 +/- 0.14 (P = 0.005).
      CONCLUSIONS: Iloprost-induced pulmonary vasodilator responses vary among children
      with PH related to congenital heart disease. The use of inhaled iloprost in the
      cardiac catheterization laboratory results in pulmonary vasoreactivity for some
      of these children particularly a reduction in PVR and the pulmonary-to-systemic
      vascular resistance ratio.

PMID- 19089968
TI  - Amplatzer occlusion of accessory ventriculopulmonary connections.
AB  - BACKGROUND: Children with complex congenital heart disease often require staged
      palliation to regulate systemic and pulmonary blood flow. Accessory sources of
      pulmonary blood flow including aortopulmonary collaterals, aortopulmonary shunts,
      and ventriculopulmonary connections following Glenn or Fontan palliation can be
      associated with elevated central venous pressures and persistent pleural
      drainage. Occlusion of accessory ventriculopulmonary connections in this setting
      has traditionally been accomplished surgically. OBJECTIVE: To review the efficacy
      of Amplatzer devices in transcatheter occlusion of accessory ventriculopulmonary
      connections in children with complex congenital heart disease. METHODS: Patients
      were identified and their records retrospectively reviewed for indication,
      procedural details, and clinical efficacy and outcome. RESULTS: Between December
      2004 and March 2008, seven patients underwent occlusion of accessory
      ventriculopulmonary connections using an Amplatzer Septal Occluder (3), an
      Amplatzer Duct Occluder (3), or an Amplatzer Vascular Plug (1). Underlying single
      ventricle physiology was present in six of these patients. The site of occlusion
      was the right ventricle to pulmonary artery (Sano) conduit in two patients, the
      native main pulmonary artery in three patients, the pulmonary valve in one
      patient, and a left ventricle to pulmonary artery homograft in one patient with
      biventricular physiology. There were no complications associated with these
      procedures. CONCLUSIONS: Amplatzer occlusion devices provide a safe and effective
      means of eliminating accessory ventriculopulmonary connections in children who
      have undergone surgical palliation of congenital heart disease.

PMID- 19089969
TI  - Stenting of a stenosed major aortopulmonary collateral artery in a baby with
      pulmonary atresia and a ventricular septal defect: rescue from critical hypoxia
      in the immediate postoperative stage of unifocalization supported by
      extracorporeal membrane oxygenation.
AB  - A 4-month baby with pulmonary atresia, ventricular septal defect, major
      aortopulmonary collateral arteries (MAPCAs) and an extremely hypoplastic central
      pulmonary artery developed critical hypoxia following right unifocalization
      combined with a right Blalock-Taussig shunt. To increase pulmonary blood flow we
      stented the left lower MAPCA during extracorporeal membrane oxygenation (ECMO)
      support. He was successfully weaned from ECMO 2 days after stenting. Percutaneous
      intervention for a stenosed MAPCA is an effective means of increasing pulmonary
      blood flow in critically hypoxic patients following unilateral unifocalization,
      even in the immediate postoperative stage.

PMID- 19089970
TI  - Electrosurgical energy in combination with a transseptal needle: a novel method
      for the creation of an atrial communication in hypoplastic left heart syndrome
      with intact atrial septum.
AB  - Neonates with hypoplastic left heart syndrome (HLHS) and intact atrial septum
      (IAS) usually present with severe acidosis and hypoxemia that necessitate
      immediate intervention to create an atrial septal defect (ASD). Transcatheter
      creation of an ASD in these patients requires transseptal puncture of a thickened
      atrial septum in the setting of a very small left atrium. We report on a novel
      method of perforating the atrial septum using radio-frequency energy in
      combination with a transseptal needle to facilitate transseptal puncture and
      subsequent stent placement in a very thick atrial septum of a newborn with
      HLHS/IAS and a small left atrium.

PMID- 19089971
TI  - Percutaneous management of acutely thrombosed hemodialysis grafts: the double
      balloon occlusion technique.
AB  - OBJECTIVES: The aim of this article is to introduce a new technique, named the
      "double balloon occlusion technique" (DBOT), for the salvage of acutely
      thrombosed grafts and to demonstrate its safety and efficacy. BACKGROUND: Acute
      thrombosis is recognized as the most common factor of acute graft failures. A
      suitably percutaneous technique should be devised to remove thrombi safely and
      effectively. Care should also be taken to prevent possible thromboembolic
      complications during procedures. Mainly composed of two balloons, the
      percutaneous DBOT has been developed to meet the clinical needs. METHODS: Thirty
      two patients with graft failures undergoing the DBOT were recruited between May
      2007 and May 2008. The DBOT is itemized in the text and a practical case
      undergoing successful DBOT is also demonstrated. RESULTS: Of the 32 DBOT
      treatments, the procedural success rate was 100% (32/32). The clinical success
      rate was 94% (30/32). One complicated case with severe hematoma resulting from a
      balloon-induced graft rupture received surgery, although the graft outflow
      restored. The mean procedure time was 92 minutes. Three patients died and two
      patients were lost within the 3-month follow-up. The 3-month graft patency rate
      was 70% (19/27). CONCLUSION: The DBOT has the potential to be operated safely and
      effectively. Preliminary results had high success rates and patency rates. With
      basic devices, it may serve as an option to rescue thrombosed grafts. More data
      are needed to identify its clinical role.

PMID- 19089972
TI  - Transient contrast encephalopathy after carotid artery stenting mimicking diffuse
      subarachnoid hemorrhage: a case report.
AB  - Several types of brain injury incurred during carotid artery stenting (CAS), such
      as embolic injury, hemodynamic events, and hemorrhage. Rapid differential
      diagnosis is important for decision making, and may help to avoid subsequent
      complications. Here, we describe a case with severe triple vessel coronary artery
      disease, who underwent right coronary artery (RCA) stenting and ad hoc left CAS.
      Patient developed neurological deficit two hours after the procedure. Brain
      computed tomography (CT) revealed diffuse cortical enhancement similar to
      subarachnoid hemorrhage (SAH). Patient recovered dramatically with complete
      resolution of contrast enhancement after four days of conservative treatment,
      final diagnosis was a rare reported case of transient contrast encephalopathy.

PMID- 19089973
TI  - Conserved amino acid networks involved in antibody variable domain interactions.
AB  - Engineered antibodies are a large and growing class of protein therapeutics
      comprising both marketed products and many molecules in clinical trials in
      various disease indications. We investigated naturally conserved networks of
      amino acids that support antibody V(H) and V(L) function, with the goal of
      generating information to assist in the engineering of robust antibody or
      antibody-like therapeutics. We generated a large and diverse sequence alignment
      of V-class Ig-folds, of which V(H) and V(L) domains are family members. To
      identify conserved amino acid networks, covariations between residues at all
      possible position pairs were quantified as correlation coefficients (phi-values).
      We provide rosters of the key conserved amino acid pairs in antibody V(H) and
      V(L) domains, for reference and use by the antibody research community. The
      majority of the most strongly conserved amino acid pairs in V(H) and V(L) are at
      or adjacent to the V(H)-V(L) interface suggesting that the ability to
      heterodimerize is a constraining feature of antibody evolution. For the V(H)
      domain, but not the V(L) domain, residue pairs at the variable-constant domain
      interface (V(H)-C(H)1 interface) are also strongly conserved. The same network of
      conserved V(H) positions involved in interactions with both the V(L) and C(H)1
      domains is found in camelid V(HH) domains, which have evolved to lack
      interactions with V(L) and C(H)1 domains in their mature structures; however, the
      amino acids at these positions are different, reflecting their different
      function. Overall, the data describe naturally occurring amino acid networks in
      antibody Fv regions that can be referenced when designing antibodies or antibody
      like fragments with the goal of improving their biophysical properties.

PMID- 19089974
TI  - Structural and functional analysis of a novel hormone-sensitive lipase from a
      metagenome library.

PMID- 19089975
TI  - Domain motions of hyaluronan lyase underlying processive hyaluronan
      translocation.
AB  - Hyaluronan lyase (Hyal) is a surface enzyme occurring in many bacterial organisms
      including members of Streptococcus species. Streptococcal Hyal primarily degrades
      hyaluronan-substrate (HA) of the extracellular matrix. This degradation appears
      to facilitate the spread of this bacterium throughout host tissues. Unlike purely
      endolytic degradation of its other substrates, unsulfated chondroitin or some
      chondroitin sulfates, the degradation of HA by Hyal proceeds by processive
      exolytic cleavage of one disaccharide at a time following an initial endolytic
      cut. Molecular dynamics (MD) studies of Hyal from Streptococcus pneumoniae are
      presented that address the enzyme's molecular mechanism of action and the role of
      domain motions for processive functionality. The analysis of extensive sub
      microsecond MD simulations of this enzyme action on HA-substrates of different
      lengths and the connection between the domain dynamics of Hyal and the
      translocation of the HA-substrate reveals that opening/closing and twisting
      domain motions of the Hyal are intimately linked to processive HA degradation.
      Enforced simulations confirmed this finding as the domain motions in SpnHyal were
      found to be induced by enforced substrate translocation. These results establish
      the dynamic interplay between Hyal flexibility and substrate translocation and
      provide insight into the processive mechanism of Hyal.

PMID- 19089977
TI  - Another look at the conditions for the extraction of protein knowledge-based
      potentials.
AB  - Protein knowledge-based potentials are effective free energies obtained from
      databases of known protein structures. They are used to parameterize coarse
      grained protein models in many folding simulation and structure prediction
      methods. Two common approaches are used in the derivation of knowledge-based
      potentials. One assumes that the energy parameters optimize the native structure
      stability. The other assumes that interaction events are related to their
      energies according to the Boltzmann distribution, and that they are distributed
      independently of other events, that is, the quasi-chemical approximation. Here,
      these assumptions are systematically tested by extracting contact energies from
      artificial databases of lattice proteins with predefined pairwise contact
      energies. Databases of protein sequences are designed to either satisfy the
      Boltzmann distribution at high or low temperatures, or to simultaneously optimize
      the native stability and folding kinetics. It is found that the quasi-chemical
      approximation, with the ideal reference state, accurately reproduce the true
      energies for high temperature Boltzmann distributed sequences (weakly interacting
      residues), but less accurately at low temperatures, where the sequences
      correspond to energy minima and the residues are strongly interacting. To
      overcome this problem, an iterative procedure for Boltzmann distributed sequences
      is introduced, which accounts for interacting residue correlations and eliminates
      the need for the quasi-chemical approximation. In this case, the energies are
      accurately reproduced at any ensemble temperature. However, when the database of
      sequences designed for optimal stability and kinetics is used, the energy
      correlation is less than optimal using either method, exhibiting random and
      systematic deviations from linearity. Therefore, the assumption that native
      structures are maximally stable or that sequences are determined according to the
      Boltzmann distribution seems to be inadequate for obtaining accurate energies.
      The limited number of sequences in the database and the inhomogeneous
      concentration of amino acids from one structure to another do not seem to be
      major obstacles for improving the quality of the extracted pairwise energies,
      with the exception of repulsive interactions.

PMID- 19089976
TI  - Combined QM/MM mechanistic study of the acylation process in furin complexed with
      the H5N1 avian influenza virus hemagglutinin's cleavage site.
AB  - Combined quantum mechanical/molecular mechanical (QM/MM) techniques have been
      applied to investigate the detailed reaction mechanism of the first step of the
      acylation process by furin in which the cleavage site of the highly pathogenic
      avian influenza virus subtype H5N1 (HPH5) acts as its substrate. The energy
      profile shows a simultaneous mechanism, known as a concerted reaction, of the two
      subprocesses: the proton transfer from Ser368 to His194 and the nucleophilic
      attack on the carbonyl carbon of the scissile peptide of the HPH5 cleavage site
      with a formation of tetrahedral intermediate (INT). The calculated energy barrier
      for this reaction is 16.2 kcal.mol(-1) at QM/MM B3LYP/6-31+G*//PM3-CHARMM22 level
      of theory. Once the reaction proceeds, the ordering of the electrostatic
      stabilization by protein environment is of the enzyme-substrate < transition
      state < INT complexes. Asp153 was found to play the most important role in the
      enzymatic reaction by providing the highest degree of intermediate complex
      stabilization. In addition, the negatively charged carbonyl oxygen of INT is well
      stabilized by the oxyanion hole constructed by Asn295's carboxamide and Ser368's
      backbone.

PMID- 19089978
TI  - Molecular dynamics studies on structure and dynamics of phospholamban monomer and
      pentamer in membranes.
AB  - Phospholamban (PLB) is an integral membrane protein of 52 residues that regulates
      the activity of the sarcoplasmic reticulum calcium pump in cardiac muscle cells
      through reversible phosphorylation of Ser16. To explore its possible
      conformations and dynamics in a monomeric state, we have performed comparative
      molecular dynamics simulations of unphosphorylated and phosphorylated PLB (pPLB)
      with various orientations in POPC membranes. The simulations indicate that
      dynamics of the cytoplasmic domain is highly dependent on its interactions with
      membranes, that is, large conformational changes in the absence of membrane
      interactions, but very restricted dynamics in their presence. pPLB shows more
      structural flexibility in its cytoplasmic domain, which is consistent with
      experimental observations. We have also performed a simulation of a PLB
      pentameric structure (the so-called bellflower model), recently determined in
      micelles, to investigate its behaviors in a POPC membrane. The cytoplasmic domain
      in each monomer shows uncorrelated dynamics and undergoes large conformational
      changes toward the membrane surface during the simulation, which supports the so
      called pinwheel model of the PLB pentamer structure. The hydrophobic nature of
      the pentameric pore excludes water molecules in the pore region, which
      illustrates that the pore appears to be an energetic barrier for ion and water
      translocation.

PMID- 19089979
TI  - Intrinsic structural disorder of mouse proNGF.
AB  - The unprocessed precursor of the Nerve Growth Factor (NGF), proNGF, has
      additional functions, besides its initially described role as a chaperone for NGF
      folding. The precursor protein endows apoptotic and/or neurotrophic properties,
      in contrast to the mature part. The structural and molecular basis for such
      distinct activities are presently unknown. Aiming to gain insights into the
      specific molecular interactions that govern rm-proNGF biological activities
      versus those of its mature counterpart, a structural study by synchrotron small
      angle X-ray scattering (SAXS) in solution was carried out. The different binding
      properties of the two proteins were investigated by surface plasmon resonance
      (SPR) using, as structural probes, a panel of anti-NGF antibodies and the soluble
      forms of TrkA and p75(NTR) receptors. SAXS measurements revealed the rm-proNGF to
      be dimeric and anisometric, with the propeptide domain being intrinsically
      unstructured. Ab initio reconstructions assuming twofold symmetry generated two
      types of structural models, a globular "crab-like" and an elongated shape that
      resulted in equally good fits of the scattering data. A novel method accounting
      for possible coexistence of different conformations contributing to the
      experimental scattering pattern, with no symmetry constraints, suggests the "crab
      like" to be a more likely proNGF conformation. To exploit the potential of
      chemical stabilizers affecting the existing conformational protein populations,
      SAXS data were also collected in the presence of ammonium sulphate. An increase
      of the proNGF compactness was observed. SPR data pinpoints that the propeptide of
      proNGF may act as an intrinsically unstructured protein domain, characterized by
      a molecular promiscuity in the interaction/binding to multiple partners (TrkA and
      p75(NTR) receptors and a panel of neutralizing anti-NGF antibodies) depending on
      the physiological conditions of the cell. These data provide a first insight into
      the structural basis for the selectivity of mouse short proNGF, versus NGF,
      towards its binding partners.

PMID- 19089980
TI  - A unified hydrophobicity scale for multispan membrane proteins.
AB  - The concept of hydrophobicity is critical to our understanding of the principles
      of membrane protein (MP) folding, structure, and function. In the last decades,
      several groups have derived hydrophobicity scales using both experimental and
      statistical methods that are optimized to mimic certain natural phenomena as
      closely as possible. The present work adds to this toolset the first knowledge
      based scale that unifies the characteristics of both alpha-helical and beta
      barrel multispan MPs. This unified hydrophobicity scale (UHS) distinguishes
      between amino acid preference for solution, transition, and trans-membrane
      states. The scale represents average hydrophobicity values of amino acids in
      folded proteins, irrespective of their secondary structure type. We furthermore
      present the first knowledge-based hydrophobicity scale for mammalian alpha
      helical MPs (mammalian hydrophobicity scale--MHS). Both scales are particularly
      useful for computational protein structure elucidation, for example as input for
      machine learning techniques, such as secondary structure or trans-membrane span
      prediction, or as reference energies for protein structure prediction or protein
      design. The knowledge-based UHS shows a striking similarity to a recent
      experimental hydrophobicity scale introduced by Hessa and coworkers (Hessa T et
      al., Nature 2007;450:U1026-U1032). Convergence of two very different approaches
      onto similar hydrophobicity values consolidates the major differences between
      experimental and knowledge-based scales observed in earlier studies. Moreover,
      the UHS scale represents an accurate absolute free energy measure for folded,
      multispan MPs--a feature that is absent from many existing scales. The utility of
      the UHS was demonstrated by analyzing a series of diverse MPs. It is further
      shown that the UHS outperforms nine established hydrophobicity scales in
      predicting trans-membrane spans along the protein sequence. The accuracy of the
      present hydrophobicity scale profits from the doubling of the number of integral
      MPs in the PDB over the past four years. The UHS paves the way for an increased
      accuracy in the prediction of trans-membrane spans.

PMID- 19089982
TI  - Defining and characterizing protein surface using alpha shapes.
AB  - The alpha shape of a molecule is a geometrical representation that provides a
      unique surface decomposition and a means to filter atomic contacts. We used it to
      revisit and unify the definition and computation of surface residues, contiguous
      patches, and curvature. These descriptors are evaluated and compared with former
      approaches on 85 proteins for which both bound and unbound forms are available.
      Based on the local density of interactions, the detection of surface residues
      shows a sensibility of 98%, whereas preserving a well-formed protein core. A
      novel conception of surface patch is defined by traveling along the surface from
      a central residue or atom. By construction, all surface patches are contiguous
      and, therefore, allows to cope with common problems of wrong and nonselection of
      neighbors. In the case of protein-binding site prediction, this new definition
      has improved the signal-to-noise ratio by 2.6 times compared with a widely used
      approach. With most common approaches, the computation of surface curvature can
      be locally biased by the presence of subsurface cavities and local variations of
      atomic densities. A novel notion of surface curvature is specifically developed
      to avoid such bias and is parametrizable to emphasize either local or global
      features. It defines a molecular landscape composed on average of 38% knobs and
      62% clefts where interacting residues (IR) are 30% more frequent in knobs. A
      statistical analysis shows that residues in knobs are more charged, less
      hydrophobic and less aromatic than residues in clefts. IR in knobs are, however,
      much more hydrophobic and aromatic and less charged than noninteracting residues
      (non-IR) in knobs. Furthermore, IR are shown to be more accessible than non-IR
      both in clefts and knobs. The use of the alpha shape as a unifying framework
      allows for formal definitions, and fast and robust computations desirable in
      large-scale projects. This swiftness is not achieved to the detriment of quality,
      as proven by valid improvements compared with former approaches. In addition, our
      approach is general enough to be applied on nucleic acids and any other
      biomolecules.

PMID- 19089981
TI  - Crystal structure of a novel archaeal AAA+ ATPase SSO1545 from Sulfolobus
      solfataricus.

PMID- 19089985
TI  - Enhanced protein fold recognition using a structural alphabet.
AB  - Fold recognition from sequence can be an important step in protein structure and
      function prediction. Many methods have tackled this goal. Most of them, based on
      sequence alignment, fail for sequences of low similarity. Alignment-free
      approaches can provide an efficient alternative. For such approaches, the
      identification of efficient fold discriminatory features is critical. We propose
      a new fold recognition approach that relies on the encoding of the local
      structure of proteins using a Hidden Markov Model Structural Alphabet. This
      encoding provides a 1D description of the conformation of complete proteins
      structures, including loops. At the fold level, compared with the classical
      secondary structure helix, strand, and coil states, such encoding is expected to
      provide the means of a better discrimination between loop conformations, hence
      providing better fold identification. Compared with previous related approaches,
      this supplement of information results in significant improvement. When combining
      this information with supplementary information of secondary structure and
      residue burial, we obtain a fold recognition accuracy of 78% for 27 protein
      families, that is, 8% higher than the best available method so far, and of 68%
      for 60 families. Corresponding scores at the class level are of 92% and 90%
      indicating that mispredictions are mostly within structural classes.

PMID- 19089986
TI  - Inclusion of ionization states of ligands in affinity calculations.
AB  - When estimating binding affinities of a ligand, which can exists in multiple
      forms, for a target molecule, one must consider all possible competing
      equilibria. Here, a method is presented that estimates the contribution of the
      protonation equilibria of a ligand in solution to the measured or calculated
      binding affinity. The method yields a correction to binding constants that are
      based on the total concentration of inhibitor (the sum of all ionized forms of
      the inhibitor in solution) to account for the complexed form of the inhibitor
      only. The method is applied to the calculation of the difference in binding
      affinity of two inhibitors, 2-phosphoglycolate (PGA) and its phoshonate analog 3
      phosphonopropionate (3PP), for the glycolytic enzyme triosephosphate isomerase.
      Both inhibitors have three titrating sites and exist in solution as a mixture of
      different forms. In this case the form that actually binds to the enzyme is
      present at relative low concentrations. The contributions of the alternative
      forms to the difference in binding energies is estimated by means of molecular
      dynamics simulations and corrections. The inhibitors undergo a pK(a) shift upon
      binding that is estimated by ab initio calculations. An interesting finding is
      that the affinity difference of the two inhibitors is not due to different
      interactions in the active site of the enzyme, but rather due to the difference
      in the solvation properties of the inhibitors.

PMID- 19089983
TI  - Energetics of calmodulin domain interactions with the calmodulin binding domain
      of CaMKII.
AB  - Calmodulin (CaM) is an essential eukaryotic calcium receptor that regulates many
      kinases, including CaMKII. Calcium-depleted CaM does not bind to CaMKII under
      physiological conditions. However, binding of (Ca(2+))(4)-CaM to a basic
      amphipathic helix in CaMKII releases auto-inhibition of the kinase. The crystal
      structure of CaM bound to CaMKIIp, a peptide representing the CaM-binding domain
      (CaMBD) of CaMKII, shows an antiparallel interface: the C-domain of CaM primarily
      contacts the N-terminal half of the CaMBD. The two domains of calcium-saturated
      CaM are believed to play distinct roles in releasing auto-inhibition. To
      investigate the underlying mechanism of activation, calcium-dependent titrations
      of isolated domains of CaM binding to CaMKIIp were monitored using fluorescence
      anisotropy. The binding affinity of CaMKIIp for the domains of CaM increased upon
      saturation with calcium, with the C-domain having a 35-fold greater affinity than
      the N-domain. Because the interdomain linker of CaM regulates calcium-binding
      affinity and contribute to conformational change, the role of each CaM domain was
      explored further by investigating effects of CaMKIIp on site-knockout mutants
      affecting the calcium-binding sites of a single domain. Investigation of the
      thermodynamic linkage between saturation of individual calcium-binding sites and
      CaM-domain binding to CaMKIIp showed that calcium binding to Sites III and IV was
      sufficient to recapitulate the behavior of (Ca(2+))(4)-CaM. The magnitude of
      favorable interdomain cooperativity varied depending on which of the four calcium
      binding sites were mutated, emphasizing differential regulatory roles for the
      domains of CaM, despite the high degree of homology among the four EF-hands of
      CaM.

PMID- 19089987
TI  - Geometric characteristics of hydrogen bonds involving sulfur atoms in proteins.
AB  - Sulfur atoms have been known to participate in hydrogen bonds (H-bonds) and these
      sulfur-containing H-bonds (SCHBs) are suggested to play important roles in
      certain biological processes. This study aims to comprehensively characterize all
      the SCHBs in 500 high-resolution protein structures (< or =1.8 A). We categorized
      SCHBs into six types according to donor/acceptor behaviors and used explicit
      hydrogen approach to distinguish SCHBs from those of nonhydrogen bonding
      interactions. It is revealed that sulfur atom is a very poor H-bond acceptor, but
      a moderately good H-bond donor. In alpha-helix, considerable SCHBs were found
      between the sulphydryl group of cysteine residue i and the carbonyl oxygen of
      residue i-4, and these SCHBs exert effects in stabilizing helices. Although for
      other SCHBs, they possess no specific secondary structural preference, their
      geometric characteristics in proteins and in free small compounds are
      significantly distinct, indicating the protein SCHBs are geometrically distorted.
      Interestingly, sulfur atom in the disulfide bond tends to form bifurcated H-bond
      whereas in cysteine-cysteine pairs prefer to form dual H-bond. These special H
      bonds remarkably boost the interaction between H-bond donor and acceptor. By
      oxidation/reduction manner, the mutual transformation between the dual H-bonds
      and disulfide bonds for cysteine-cysteine pairs can accurately adjust the
      structural stability and biological function of proteins in different
      environments. Furthermore, few loose H-bonds were observed to form between the
      sulphydryl groups and aromatic rings, and in these cases the donor H is almost
      over against the rim rather than the center of the aromatic ring.

PMID- 19089988
TI  - Anatomical considerations of the deep peroneal nerve for biopsy of the proximal
      fibula in Thais.
AB  - The present research aims to study the anatomical relationship between the deep
      peroneal nerve and the neighboring structures in the proximal fibula of Thais,
      with special regard to define the boundaries of a "safe" area when performing a
      biopsy of the proximal fibula. The proximal parts of 118 legs of 59 formalin
      embalmed adult cadavers (31 males, 28 females) were investigated. The distance
      from the apex of the fibular head to the point of origin of the deep peroneal
      nerve, the distance from the most lateral prominence of the fibular head to the
      anterior intermuscular septum, and the angle between the deep peroneal nerve and
      the fibula axis were measured. The results showed that the mean distances from
      the apex of the fibular head to the point of origin of the deep peroneal nerve
      was 28.4 +/- 4.8 mm and from the most lateral prominence of the fibular head to
      the anterior intermuscular septum was 14.9 +/- 2.0 mm. The mean angle between the
      deep peroneal nerve and the fibular axis was 28.1 degrees +/- 7.2 degrees . In
      conclusion, these findings suggest that a "safe" area for bone biopsy in the
      proximal fibula of Thais is palpable anterior to the fibular head and downward
      laterally, not lower than 28 mm or 8% of the fibular length and from the most
      lateral prominence transverse medially not further than 14 mm. The inferior
      boundary of this area is an oblique line of the deep peroneal nerve about 28
      degrees from the fibular axis.

PMID- 19089989
TI  - The applied anatomy of anterior approach for minimally invasive hip joint
      surgery.
AB  - The anterior approach for minimally invasive hip joint surgery is one of the
      common approaches utilized in hip joint surgery. Here, we report the results of
      dissections in 60 sides of human adult cadavers. We observed and measured the
      branches of the superficial circumflex iliac artery, the lateral femoral
      cutaneous nerves, the lateral circumflex femoral artery, and the superior gluteal
      nerves in the experiment via the anterior approach for minimally invasive hip
      joint surgery. The relationship between these structures and the anterior
      approach was studied. The present study provides important data demonstrating the
      location, path of dominant structures that might be encountered during the
      surgery and their relationships with the surgical incision. These data may allow
      surgeons performing the anterior approach for hip joint surgery to minimize the
      risk of neurovascular injury.

PMID- 19089990
TI  - The tympanic segment of the facial nerve: anatomical study.
AB  - There is a conroversy in the literature about the length of the proximal tympanic
      segment of the facial nerve (PTSFN). The objective of the current study is to
      measure the length of the tympanic segment of the facial nerve (TSFN) and of its
      proximal (PTSFN) and distal (DTSFN) segments, in normal human temporal bones.
      Moreover, we will explore if these lengths are correlated. If a form of a
      functional relationship can be established, it could offer insights in partially
      predicting or estimating the length of the TSFN as well as of its proximal and
      distal portions. Direct measurements were obtained in 40 normal human temporal
      bones, which were examined by surgical dissection. Relationships between these
      measurements were established using Pearson's correlation method (two-tailed).
      The length of the TSFN was on average 10.97 mm. The length of the PTSFN was on
      average 5.25 mm and of the DTSFN was 5.72 mm. No significant statistical
      differences according to gender or side (right or left) were detected. It was
      determined that the length of the TSFN was in linear correlation with positive
      direction with its proximal (PTSFN) and distal (DTSFN) segments. Also the PTSFN
      length was in linear correlation with positive direction with the DTSFN length.
      The length of the PTSFN comprises about one-half of the TSFN length. The
      existence of a definite correlation between the lengths of the TSFN, PTSFN, and
      DTSFN implies the existence of a form of functional interrelationship. This could
      facilitate prediction and identification of the TSFN and PTSFN lengths from the
      easily identifiable DTSFN length during surgery.

PMID- 19089991
TI  - On medical research and human dignity.

PMID- 19089992
TI  - Expression of proinflammatory cytokines by human mesenchymal stem cells in
      response to cyclic tensile strain.
AB  - Mesenchymal stem cells produce proinflammatory cytokines during their normal
      growth. Direct or indirect regulation of bone resorption by these cytokines has
      been reported. However, the effects of osteogenic conditions-chemical and/or
      mechanical-utilized during in vitro bone tissue engineering on expression of
      cytokines by hMSCs have not been studied. In this study, we investigated the
      effects of cyclic tensile strain, culture medium (with and without
      dexamethasone), and culture duration on the expression of tumor necrosis factor
      alpha (TNF-alpha), interleukin-1 beta (IL-1 beta), interleukin-6 (IL-6), and
      interleukin-8 (IL-8) by bone marrow derived human mesenchymal stem cells (hMSCs).
      Human MSCs seeded in three-dimensional Type I collagen matrices were subjected to
      0%, 10%, and 12% uniaxial cyclic tensile strains at 1 Hz for 4 h/day for 7 and 14
      days in complete growth or dexamethasone-containing osteogenic medium. Viability
      of hMSCs was maintained irrespective of strain level and media conditions.
      Expression of either TNF-alpha or IL-1 beta was not observed in hMSCs under any
      of the conditions investigated in this study. Expression of IL-6 was dependent on
      culture medium. An increase in IL-6 expression was caused by both 10% and 12%
      strain levels. Both 10% and 12% strain levels caused an increase in IL-8
      production by hMSCs that was dependent on the presence of dexamethasone. IL-6 and
      IL-8 expressions by hMSCs were induced by cyclic tensile strain and osteogenic
      differentiating media, indicating that IL-6 and IL-8 may be functioning as
      autocrine signals during osteogenic differentiation of hMSCs.

PMID- 19089993
TI  - A novel role of ERK5 in integrin-mediated cell adhesion and motility in cancer
      cells via Fak signaling.
AB  - In metastatic cancer, high expression levels of vitronectin (VN) receptors
      (integrins), FAK, and ERK5 are reported. We hypothesized that integrin-mediated
      ERK5 activation via FAK may play a pivotal role in cell adhesion, motility, and
      metastasis. ERK5 and FAK phosphorylation when metastatic MDA-MB-231 and PC-3
      cells were plated on VN was enhanced. Further experiments showed co
      immunoprecipitation of integrins beta1, alpha V beta 3, or alpha V beta 5 with
      ERK5 and FAK. To gain better insight into the mechanism of ERK5, FAK, and VN
      receptors in cell adhesion and motility, we performed loss-of-function
      experiments using integrin blocking antibodies, and specific mutants of FAK and
      ERK5. Ectopic expression of dominant negative ERK5/AEF decreased ERK5 and FAK
      (Y397) phosphorylation, cell adhesion, and haptotactic motility (micromotion) on
      VN. Additionally, DN FAK expression attenuated ERK5 phosphorylation, cell
      adhesion, and motility. This study documents the novel finding that in breast and
      prostate cancer cells, ERK5 is a critical target of FAK in cell adhesion
      signaling. Using different cancer cells, our experiments unveil a novel mechanism
      by which VN receptors and FAK could promote cancer metastasis via ERK5
      activation.

PMID- 19089994
TI  - Overexpression of delta Np63 in a human nasopharyngeal carcinoma cell line
      downregulates CKIs and enhances cell proliferation.
AB  - p63 belongs to a member of the tumor suppressor protein p53 family. Due to
      alternative promoter usage, two types of p63 proteins are produced. The DeltaNp63
      isoform lacks the N-terminal transactivation domain and is thought to antagonize
      TAp63 and p53 in target gene regulation. DeltaNp63 has been found to be
      overexpressed in numerous human squamous cell carcinomas, including
      nasopharyngeal carcinoma (NPC). However, the role of DeltaNp63 overexpression in
      NPC pathogenesis has not been clear. In this study, we use a DeltaNp63
      overexpressing human NPC cell line (NPC-076) to explore the possible roles of
      DeltaNp63 in cell proliferation and cell-cycle regulation. We found that the
      proliferation of NPC-076 cell is greatly suppressed when the overexpressed
      DeltaNp63 is silenced by specific DeltaNp63 siRNA. Further studies show that
      DeltaNp63 silencing results in the upregulation of CKIs, including p27(kip1) and
      p57(kip2) in both mRNA and protein levels. Cell-cycle analysis shows that
      DeltaNp63 silencing also results in an increased G1 phase cell and apoptotic cell
      population. Our findings indicate that DeltaNp63 plays important roles in the
      regulation of NPC-076 cell-cycle progression, and may play a role in the
      maintenance of NPC-076 tumor cell phenotype.

PMID- 19089995
TI  - Where new approaches can stem from: focus on stem cell identification.

PMID- 19089996
TI  - An anatomical study with clinical application of one branch of the
      supraclavicular artery.
AB  - The supraclavicular flap is an important method for the reconstruction of the
      neck. In this study, the authors attempted to clarify the mechanism of blood flow
      into the supraclavicular flap based on the thoracic branch of the supraclavicular
      artery. Additionally, the authors discuss the clinical application of such
      anatomy. Thirty fresh cadavers and 13 preserved cadavers were dissected to
      observe the anatomic features of the pectorally extended supraclavicular flap.
      Additionally, 46 clinical cases were treated with such a flap. We identified two
      branches of the supraclavicular artery. A deltoid branch that extended to the
      acromial region and a thoracic branch that traveled to the anterior thoracic
      region. Using these data, all such flaps operated by us have to date, survived
      with satisfactory results. The pectorally extended supraclavicular flap could be
      used to repair defects on the ipsilateral or contralateral face, neck, and
      anterior thorax.

PMID- 19089997
TI  - Radiographic evaluation of frontal talar edge configuration for osteochondral
      plug transplantation.
AB  - For successful reconstruction of osteochondral lesions of the talus, the anatomic
      configuration of the talar edge must be respected. This study evaluated the
      radiographic configuration of the talar edge in the anterior-posterior (AP) view
      by analyzing medial and lateral talar edge angles and radii in 81 patients with a
      true AP view and without ankle pathology. The mean lateral talar edge angle was
      91.8 degrees , and the mean medial talar edge angle was 110.0 degrees . The
      medial frontal talar edge radius was 4.8 mm and the lateral 3.5 mm, respectively.
      No correlation between angle and radius was found. These results revealed a
      significant difference between the medial and the lateral talar edge
      configuration. This may be due to the three-dimensional function of the human
      ankle joint. No study so far has addressed these differences radiologically.
      These differences should be addressed in the reconstruction of osteochondral
      lesions and be included in the preoperative planning.

PMID- 19089998
TI  - The marginal mandibular branch of the facial nerve in Koreans.
AB  - The marginal mandibular branch (MMB) has a particular risk of injury during
      surgical procedures in the submandibular region, especially over the lower border
      of the mandible. The facial nerve has been described in many studies, but the MMB
      is dealt with generally as a branch of the facial nerve. The purpose of this
      study was to document the anatomy of the MMB by correlation with anatomical
      landmarks. Eighty-five facial halves were examined for this study. The MMB was
      classified according to the number of branches and their connections with other
      branches, and by its relationship with landmarks of the gonion, facial artery,
      and retromandibular vein. The MMB showed one (28%), two (52%), three (18%), or
      four branches (2%) where it exited the parotid gland. Classification was based on
      connection with other branches. Type I (60%) did not communicate with other
      branches. Type II (40%) communicated with the buccal or cervical branches, or
      with another branch of the MMB. The cervicofacial division coursed along the
      lateral aspect of the retromandibular vein in 83% of specimens. The MMB passed
      the facial artery superficially (42%), passed it deeply in 4%, and ran on both
      sides of it in 54% of the facial halves. The distribution of the MMB formed a
      quadrilateral with angles +19.8 mm, -8.1 mm, +30.0 mm, and -15.3 mm measured from
      two sides on the inferior border of the mandible. These topographical data should
      help to decrease the incidence of injuries during surgery on the submandibular
      regions in Koreans.

PMID- 19089999
TI  - Colosigmoid junction: morphohistologic, morphometric, and endoscopic study with
      identification of colosigmoid canal with sphincter.
AB  - To study the anatomical structure of the colosigmoid junction, 15 cadaveric
      specimens were studied morphologically, another 15 histologically, and a
      morphometric study was done in 10 specimens. Specimens consisted of the
      descending colon, sigmoid colon, and the colosigmoid junction. Histologic
      specimens were stained with hematoxylin and eosin and Masson's trichrome stain.
      Morphometric studies used an image analysis system. The colosigmoid junction was
      investigated endoscopically in 18 healthy volunteers. A narrow segment having a
      mean length of 5.2 +/- 1.1 cm was identified both externally and internally
      between the descending and sigmoid colon. We called this segment the colosigmoid
      canal. Mucosal folds were found crowded in the colosigmoid canal, the lower end
      of which formed a nipple and was surrounded by a fornix. Histologically, the
      colosigmoid canal mucosa showed multiple folds. Its circular muscle was thicker
      than that of the descending or the sigmoid colon and confirmed morphometrically.
      The longitudinal muscle was thicker in only 4 of 10 specimens. Both the narrowing
      and the mucosal crowding were verified endoscopically. The colosigmoid junction
      is the narrow segment between the descending and the sigmoid colon. Histologic,
      morphometric and endoscopic studies indicated the presence of a sphincter in the
      colosigmoid canal. A colosigmoid sphincter is suggested to control the passage of
      colonic contents from the descending colon to the colosigmoid canal as well as to
      prevent reflux of sigmoid contents into the descending colon.

PMID- 19090000
TI  - Do the vastus medialis obliquus and vastus medialis longus really exist? A
      systematic review.
AB  - There remains controversy over whether the vastus medialis (VM) is a single
      anatomical structure or whether it is composed of two separate portions, the
      vastus medialis longus (VML) proximally and the vastus medialis obliquus (VMO)
      distally. The objective of this study was to assess the evidence base of
      investigations into muscle fiber orientation, presence of a fibrofascial plane,
      and the innervation of the VM in human cadaver specimens and subjects. In
      addition to a hand search of specialist journals, an electronic search of AMED,
      British Nursing Index, CINAHL, the Cochrane database, EMBASE, ovid Medline,
      Pubmed, and Zetoc were performed from their inception to September 2008. All
      human subject papers assessing VM fiber orientation, presence of a fibrofascial
      plane, and the innervation of the VM where reviewed. Twenty-six papers, assessing
      699 healthy knees, and 591 specimens with patellofemoral dysfunction were
      reviewed. The majority of nonpathological and pathological cases presented with a
      substantial alteration in fiber alignment seen between proximal and distal muscle
      portions of VM. Both cohorts presented with either one or two nerve branches to
      the VM. A fibrofascial plane dividing these two muscles was seen in a small
      proportion of both pathological and nonpathological knees. There was, however,
      insufficient good quality evidence to state whether the VM is composed of two
      separate components, the proximal VML and the distal VMO. Further study is
      recommended to evaluate the pathophysiological implications of such findings and
      to assess whether these correlate to functional electromyographic findings
      between the VML and VMO muscles.

PMID- 19090001
TI  - Reverse total shoulder arthroplasty.
AB  - Reverse total shoulder arthroplasty designs have gained popularity over the last
      few years due to their satisfactory functional results in patients with cuff-tear
      arthropathy and other difficult reconstructive shoulder problems. These
      semiconstrained prostheses improve stability and active elevation in the absence
      of a functional rotator cuff by coupling a spherical glenoid component with a
      concave humeral component and increasing deltoid tension. Understanding the
      anatomy of the shoulder is critical in order to ensure secure fixation of the
      glenoid component, explore uncemented options for humeral component fixation, and
      determine the ideal soft-tissue tension to provide the best functional outcome
      without increasing the risk of complications. Key anatomic elements to be
      considered for the successful implantation of a reverse prosthesis include the
      orientation and size of the glenoid vault, the scapular regions with better bone
      stock (coracoid, spine of the scapula), the internal geometry of the humeral
      medullary canal, and the effects of reverse arthroplasty on the deltoid and
      brachial plexus.

PMID- 19090002
TI  - The course and variations of the branches of the musculocutaneous nerve in human
      fetuses.
AB  - The course and branches of the musculocutaneous nerve (MCN) were dissected in 140
      human fetal arms. The MCN entered the superior, middle, and inferior part of
      coracobrachialis in 43%, 37%, and 17% of arms, respectively, and the remaining 3%
      did not pierce coracobrachialis. The motor branches to biceps were classified as
      follows: Type 1 (83.6%): a single branch that bifurcated to supply the two heads
      of biceps; Type 2 (14.3%): two separate branches each innervating one head of
      biceps; Type 3 (2.1%): a single branch that bifurcated to supply each head of
      biceps plus an additional branch that innervated the distal part of biceps. The
      motor branches to brachialis were classified as follows: Type 1 (93.6%): a single
      branch to brachialis; Type 2 (6.4%): a single branch that bifurcated into two
      branches both supplying brachialis. Communications between the MCN and the median
      nerve (MN) were observed in 10% of specimens, of which three types (A, B, C)
      could be identified depending on their origin and union. In the most frequently
      observed type (B, 50% of cases) the communicating branch arose from the proximal
      part of the MCN and joined the MN in the middle or distal part of arm. The data
      presented here will be of use to surgeons, especially pediatric surgeons who
      undertake surgical procedures in the axilla and arm.

PMID- 19090003
TI  - Herpes simplex virus lower respiratory tract infection in patients with solid
      tumors.
AB  - BACKGROUND: The clinical significance of herpes simplex virus (HSV) isolated in
      lower respiratory tract specimens (LRTS) of patients with solid tumors (ST) is
      unknown. In the current study, the authors attempted to determine the clinical
      relevance of this finding among ST patients. METHODS: The authors reviewed
      records of ST patients admitted to the study institution between April 2000 and
      April 2004 with clinical and radiologic evidence of pneumonia, and HSV identified
      in LRTS by culture alone or culture and cytology. Patients were categorized as
      having proven (HSV identified by culture and cytology from the LRTS), probable
      (HSV as the sole pathogen by culture alone), and possible (HSV along with
      copathogens identified by culture) HSV pneumonia. RESULTS: Forty-five ST patients
      with either proven (6 patients), probable (25 patients), or possible (14
      patients) HSV pneumonia were identified. When compared with patients with
      probable or possible HSV pneumonia, more patients with proven infection were on
      mechanical ventilation (40% vs 50% vs 100%, respectively; P=.03), and had longer
      length of stay in the intensive care unit (12 days vs 13 days vs 26 days,
      respectively; P=.05). The overall mortality rate was 22% (10 patients). Four of
      25 (16%) patients who received HSV-directed antiviral therapy died during their
      hospital stay versus 6 of 20 (30%) who were not treated (P=.3). None of the 6
      patients with proven HSV pneumonia who were treated with acyclovir died. On
      univariate analysis, risk factors for mortality included underlying breast
      cancer, an Acute Physiology and Chronic Health Evaluation (APACHE) II score>15,
      admission to the intensive care unit, and use of mechanical ventilation and
      vasopressors (all P<or=.05), with underlying breast cancer and APACHE II score>15
      being found to be independent predictors of death by multiple logistic regression
      analysis (all P<or=.05). CONCLUSIONS: Having a proven HSV pneumonia appears to be
      associated with high morbidity and with no increase in mortality in ST patients.
      This subset of patients appears to benefit from acyclovir therapy.

PMID- 19090004
TI  - Acyclovir to prevent reactivation of varicella zoster virus (herpes zoster) in
      multiple myeloma patients receiving bortezomib therapy.
AB  - BACKGROUND: Humoral-mediated as well as cell-mediated immunity is compromised in
      myeloma patients receiving treatment. Immunocompromised patients are at risk of
      developing herpes zoster. There is evidence from clinical trials that bortezomib
      therapy is associated with a significant risk of herpes zoster. It is the
      authors' clinical policy to administer long-term acyclovir prophylactically to
      all symptomatic myeloma patients. METHODS: A retrospective review of the records
      of 125 myeloma patients who were treated with bortezomib and who also received
      routine acyclovir prophylaxis at the dose of 400 mg daily in >80% of patients was
      undertaken. Alternatives, used in <20% of patients, were 200 mg of acyclovir,
      250/500 mg of valacyclovir, or 500 mg of famciclovir administered daily. This was
      accompanied by patient education regarding the importance of compliance with
      these prophylactic medications. RESULTS: The duration of bortezomib therapy was 1
      to 164 weeks (median, 16 weeks). The total duration of exposure to bortezomib was
      4150 weeks (80 patient-years). Except for the occasional missed dose, the self
      reported compliance with antiviral prophylaxis was 100%. Not a single episode of
      herpes zoster was reported during this period. No adverse effects were noted that
      could be definitely attributed to acyclovir, valacyclovir, or famciclovir.
      CONCLUSIONS: Daily acyclovir (or a suitable alternative) appears to be effective
      at preventing herpes zoster virus in patients with myeloma who are receiving
      bortezomib, with or without corticosteroids.

PMID- 19090005
TI  - Therapy-related acute myelogenous leukemia and myelodysplastic syndrome in
      patients with acute lymphoblastic leukemia treated with the hyperfractionated
      cyclophosphamide, vincristine, doxorubicin, and dexamethasone regimens.
AB  - BACKGROUND: Secondary malignancies including myeloid neoplasms occur infrequently
      in acute lymphoblastic leukemia (ALL) and to the authors' knowledge have not been
      as well documented in adults as in children. METHODS: A total of 641 patients
      with de novo ALL who were treated with the hyper-CVAD (hyperfractionated
      cyclophosphamide, vincristine, doxorubicin, and dexamethasone) regimen or its
      variants were analyzed. RESULTS: Sixteen patients (2.49%) developed secondary
      acute myelogenous leukemia (AML) (6 patients) or myelodysplastic syndrome (MDS)
      (10 patients). At the time of ALL diagnosis, the median age was 53 years;
      cytogenetics were normal in 11 patients, pseudo-diploidy with del(2) in 1
      patient, t(9;22) in 1 patient, and unavailable in 3 patients. Frontline therapy
      included hyper-CVAD in 7 patients, hyper-CVAD with rituximab in 8 patients, and
      hyper-CVAD with imatinib in 1 patient. Karyotype at time of AML/MDS diagnosis was
      -5, -7 in 9 patients, normal in 1 patient, complex in 1 patient, inv(11) in 1
      patient, t(4;11) in 1 patient, del(20) in 1 patient, and unavailable in 2
      patients. Secondary AML/MDS developed at a median of 32 months after ALL
      diagnosis. Cytarabine plus anthracycline-based treatment was given to 12 patients
      with AML and high-risk MDS. One patient with MDS received arsenic trioxide, 1
      received clofarabine, and 2 received decitabine. Response to treatment was
      complete remission in 3 patients, partial remission in 6 patients, and no
      response in 6 patients; 1 patient was untreated. Eight patients (1 with AML and 7
      with MDS) underwent allogeneic stem cell transplantation, and all but 2 died at a
      median of 3 months (range, 0.5-11 months) after transplantation. The median
      overall survival after a diagnosis of secondary AML and MDS was 9.25 months
      (range, 1+ to 26+ months). CONCLUSIONS: Secondary AML and MDS occur infrequently
      in adult patients with de novo ALL treated with the hyper-CVAD regimens, and
      response to therapy is poor.

PMID- 19090006
TI  - Critical and diverse involvement of Akt/mammalian target of rapamycin signaling
      in human lung carcinomas.
AB  - BACKGROUND: Aberrant signaling cascades emanating from epidermal growth factor
      receptor (EGFR) are involved in the complex network of oncogenic signaling in
      lung carcinomas. One representative cascade is the phosphatidylinositol 3
      kinase/Akt/mammalian target of rapamycin (mTOR) pathway. METHODS: The authors
      investigated the involvement of mTOR in the pathobiologic profiles of 150
      specimens of lung carcinoma by immunohistochemistry and immunoblotting in
      correlation with the upstream and downstream proteins Akt and p70S6-kinase (S6K),
      respectively. RESULTS: Immunohistochemistry revealed Akt activation in 44% of
      tumors and mTOR expression in 68.7% of tumors, and the preponderance of
      activation was observed in adenocarcinoma (AC) (100%). Phosphorylated mTOR (p
      mTOR) was observed in 53.3% of tumors and had the highest frequency in AC
      (89.7%). In AC, the frequency of p-mTOR staining was higher in the well
      differentiated subtype, in particular, in the acinar structure. However, little
      correlation was observed between the activation of mTOR and Akt, except in the 5
      AC specimens that harbored an EGFR gene mutation, which exhibited constitutive
      activation of both Akt and mTOR. Conversely, in squamous cell carcinomas, mTOR
      activation was associated with a significantly higher frequency of lymph node
      metastasis. CONCLUSIONS: The results of this study suggested the dual functions
      of mTOR. First, mTOR may function not only in the proliferation of tumor cells as
      an effector molecule downstream of EGFR but also possibly in the morphogenesis of
      AC. Second, the activation of mTOR may play a key role in metastasis in squamous
      cell carcinoma. Overall, the current results demonstrated the potential for the
      application of rapamycin, an mTOR inhibitor, as an additional novel component of
      chemotherapy for a defined subset of patients with lung carcinoma.

PMID- 19090007
TI  - Tumor vasculature-targeted delivery of tumor necrosis factor-alpha.
AB  - BACKGROUND: Recently, considerable efforts have been directed toward antivascular
      therapy as a new modality to treat human cancers. However, targeting a
      therapeutic gene of interest to the tumor vasculature with minimal toxicity to
      other tissues remains the objective of antivascular gene therapy. Tumor necrosis
      factor-alpha (TNF-alpha) is a potent antivascular agent but has limited clinical
      utility because of significant systemic toxicity. At the maximum tolerated doses
      of systemic TNF-alpha, there is no meaningful antitumor activity. Hence, the
      objective of this study was to deliver TNF-alpha targeted to tumor vasculature by
      systemic delivery to examine its antitumor activity. METHODS: A hybrid adeno
      associated virus phage vector (AAVP) was used that targets tumor endothelium to
      express TNF-alpha (AAVP-TNF-alpha). The activity of AAVP-TNF-alpha was analyzed
      in various in vitro and in vivo settings using a human melanoma tumor model.
      RESULTS: In vitro, AAVP-TNF-alpha infection of human melanoma cells resulted in
      high levels of TNF-alpha expression. Systemic administration of targeted AAVP-TNF
      alpha to melanoma xenografts in mice produced the specific delivery of virus to
      tumor vasculature. In contrast, the nontargeted vector did not target to tumor
      vasculature. Targeted AAVP delivery resulted in expression of TNF-alpha,
      induction of apoptosis in tumor vessels, and significant inhibition of tumor
      growth. No systemic toxicity to normal organs was observed. CONCLUSIONS: Targeted
      AAVP vectors can be used to deliver TNF-alpha specifically to tumor vasculature,
      potentially reducing its systemic toxicity. Because TNF-alpha is a promising
      antivascular agent that currently is limited by its toxicity, the current results
      suggest the potential for clinical translation of this strategy.

PMID- 19090008
TI  - Validation of a new prognostic index for patients with chronic lymphocytic
      leukemia.
AB  - BACKGROUND: The clinical course of chronic lymphocytic leukemia (CLL) is highly
      variable. A prognostic index based on widely available clinical and laboratory
      features was recently developed to predict survival among patients with
      previously untreated CLL. This index requires validation in an independent series
      of patients before widespread use can be recommended. METHODS: The Mayo Clinic
      CLL database was used to evaluate the validity and reproducibility of the new
      prognostic index. RESULTS: A total of 440 patients with newly diagnosed CLL who
      were seen at the Mayo Clinic within 12 months of diagnosis and for whom data were
      available with which to calculate index score were identified. Patients were
      classified as low, intermediate, or high risk using the prognostic index. The
      estimated median survival times were: not reached for low risk, 10.1 years for
      intermediate risk, and 7.2 years for high risk. The estimated median and 5-year
      survival by prognostic index risk category were similar to those originally
      reported. The prognostic index risk category added predictive value beyond that
      of Rai risk alone (P=.004). The prognostic index risk category remained a
      predictor of survival when analysis was limited to Rai stage 0 (P=.03) and
      nonreferred patients (P<.0001) and also predicted time to treatment (P<.0001).
      CONCLUSIONS: The results of the current study confirm the ability of a newly
      developed prognostic index to predict survival among patients with previously
      untreated CLL. The study also extended the utility of the index by demonstrating
      that it is useful at diagnosis, retains prognostic value when applied exclusively
      to Rai stage 0 patients, is effective in nonreferred patients, and predicts time
      to treatment.

PMID- 19090009
TI  - Phase 2 trial of carboplatin, weekly paclitaxel, and biweekly bevacizumab in
      patients with unresectable stage IV melanoma: a North Central Cancer Treatment
      Group study, N047A.
AB  - BACKGROUND: Vascular endothelial growth factor (VEGF) plays an important role in
      the growth and metastatic progression of melanoma. Exposure of melanoma cells to
      chemotherapy induces VEGF overproduction, which in turn may allow melanoma cells
      to evade cell death and become chemotherapy resistant. Therefore, in patients
      with metastatic melanoma, the combination of chemotherapy with an agent that
      specifically targets VEGF might be able to control tumor growth and progression
      more effectively than chemotherapy alone. METHODS: A 2-stage phase 2 clinical
      trial was conducted in patients with unresectable stage IV (metastatic) melanoma
      to assess antitumor activity and the toxicity profile of the combination of
      carboplatin (area under the curve 6 iv on Day 1 of a 28-day cycle), paclitaxel
      (80 mg/m2 iv on Days 1, 8, and 15), and bevacizumab (10 mg/kg iv on Days 1 and
      15). Treatment was continued until progression or intolerable toxicity. RESULTS:
      Fifty-three patients (62.3% male) were enrolled. Nine (17%) patients achieved
      partial remission, and another 30 (57%) achieved stable disease for at least 8
      weeks. Median progression-free survival and median overall survival were 6 months
      and 12 months, respectively. One patient died after 8 treatment cycles from
      intracranial hemorrhage into undiagnosed brain metastases. The most common severe
      (grade>or=3) toxicities were neutropenia (53%), thrombocytopenia (11%),
      hypertension (9%), and anemia (8%). CONCLUSIONS: This combination of carboplatin,
      paclitaxel, and bevacizumab appears to be moderately well tolerated and
      clinically beneficial in patients with metastatic melanoma. Further study of this
      combination is warranted.

PMID- 19090010
TI  - Influence of compartmental involvement on the patterns of morbidity in soft
      tissue sarcoma of the thigh.
AB  - BACKGROUND: The authors sought to determine whether differences existed in
      patterns of outcome and morbidity between the 3 thigh compartments after limb
      sparing surgery and postoperative radiation therapy (RT). METHODS: A total of 255
      patients with primary soft tissue sarcoma (STS) of the thigh were identified in
      our sarcoma database (1982-2002). More than 80% of tumors were >5 cm, high grade,
      and deep; 33% had close or positive microscopic resection margins. Adjuvant RT
      consisted of brachytherapy alone (BRT; 63%), external beam RT alone (EBRT; 31%),
      or a combination of brachytherapy and EBRT (6%). There were 125 anterior, 58
      medial, and 72 posterior lesions. The 3 compartments were balanced as to tumor
      grade, size, depth, margin status, and RT type. RESULTS: Overall local control
      (LC) was 89%, distant metastases-free survival (DMFS) was 61%, and overall
      survival (OS) was 66% at 5 years (median follow-up, 71 months). Overall rates for
      complications at 5 years were wound reoperation (10%), edema (13%), joint
      stiffness (12%), nerve damage (8%), and bone fractures (7%). Wound reoperation
      and edema were significantly higher for medial-compartment tumors (P=.01 and
      .005, respectively), whereas nerve damage occurred more frequently in posterior
      compartment tumors (P<.001). There were no differences among bone fracture, joint
      stiffness, DMFS, or OS rates between compartments. CONCLUSIONS: Although tumor
      control was similar for all 3 compartments, more wound reoperation and edema were
      observed in the medial compartment, and more nerve damage was noted in the
      posterior compartment. These results may help guide decisions concerning current
      patients and improve the design of future treatments tailored to compartments.

PMID- 19090011
TI  - Method of oocyte activation affects cloning efficiency in pigs.
AB  - The following experiments compared the efficiency of three fusion/activation
      protocols following somatic cell nuclear transfer (SCNT) with porcine somatic
      cells transfected with enhanced green fluorescent protein driven by the chicken
      beta-actin/rabbit beta-globin hybrid promoter (pCAGG-EGFP). The three protocols
      included electrical fusion/activation (NT1), electrical fusion/activation
      followed by treatment with a reversible proteasomal inhibitor MG132 (NT2) and
      electrical fusion in low Ca(2+) followed by chemical activation with
      thimerosal/dithiothreitol (NT3). Data were collected at Days 6, 12, 14, 30, and
      114 of gestation. Fusion rates, blastocyst-stage mean cell numbers, recovery
      rates, and pregnancy rates were calculated and compared between protocols. Fusion
      rates were significantly higher for NT1 and NT2 compared to NT3 (P < 0.05). There
      was no significant difference in mean nuclear number. Pregnancy rate for NT2 was
      100% (n = 19) at all stages collected and was significantly higher than NT1
      (71.4%, n = 28; P < 0.05), but was not significantly higher than NT3 (82.6%, n =
      23; P < 0.15). Recovery rates were calculated based on the number of embryos,
      conceptuses, fetuses, or piglets present at the time of collection, divided by
      the number of embryos transferred to the recipient gilts. Recovery rates between
      the three groups were not significantly different at any of the stages collected
      (P > 0.05). All fusion/activation treatments produced live, pCAGG-EGFP positive
      piglets from SCNT. Treatment with MG132 after fusion/activation of reconstructed
      porcine embryos was the most effective method when comparing the overall
      pregnancy rates. The beneficial effect of NT2 protocol may be due to the
      stimulation of proteasomes that infiltrate donor cell nucleus shortly after
      nuclear transfer.

PMID- 19090012
TI  - Phase 1 and pharmacokinetic study of concurrent carboplatin and irinotecan in
      subjects aged 1 to 21 years with refractory solid tumors.
AB  - BACKGROUND: Preclinical testing suggests the combination of carboplatin and
      irinotecan has at least additive antitumor activity. The primary objectives of
      the current study were to determine the maximum tolerated doses (MTDs) and
      recommended phase 2 doses of carboplatin administered with irinotecan to
      pediatric patients with refractory solid tumors. METHODS: This was a multicenter,
      open-label, single-arm dose escalation study in which subjects with refractory
      solid tumors received 21-day treatment cycles of intravenous carboplatin on Day 1
      followed by intravenous irinotecan administered daily for 10 days within 2
      consecutive weeks. The plasma pharmacokinetics of ultrafiltrable platinum,
      irinotecan, and 2 irinotecan metabolites were determined during Cycle 1. The
      interpatient plan for dose escalation at study initiation was to increase
      irinotecan first followed by increases in carboplatin. RESULTS: Twenty-eight
      patients with a median age of 8.5 years (range, 1-21 years) were enrolled with a
      variety of solid tumors. Two of 6 subjects at the first dose level (carboplatin
      target area under the curve [AUC], 4.0 mg/mL*min; irinotecan, 18 mg/m2/dose)
      experienced dose-limiting gastrointestinal toxicities requiring a dose de
      escalation scheme (carboplatin AUC, 4.0 mg/mL*min; irinotecan, 15 mg/m2/dose).
      Three of 6 subjects at the second dose level experienced dose-limiting
      gastrointestinal complications and bone marrow suppression. A further dose de
      escalation to carboplatin AUC of 4.0 mg/mL*min and irinotecan of 12 mg/m2/dose
      resulted in dose-limiting bone marrow suppression in 1 of 13 patients treated at
      that dose, and therefore was determined to be the MTD. One complete response (in
      a patient with medulloblastoma) and 3 partial responses (in patients with
      neuroblastoma, medulloblastoma, and lymphoendothelial carcinoma, respectively)
      were observed. CONCLUSIONS: The recommended phase 2 dose in heavily pretreated
      pediatric patients is carboplatin (AUC, 4 mg/mL*min on Day 1) and irinotecan (12
      mg/m2/dayx10 days) given every 21 days.

PMID- 19090013
TI  - Timing of consent for the research use of surgically removed tissue: is
      postoperative consenting acceptable?

PMID- 19090014
TI  - Sex and race in bladder cancer: what we have learned and future directions.

PMID- 19090015
TI  - Mammary serine protease inhibitor inhibits epithelial growth factor-induced
      epithelial-mesenchymal transition of esophageal carcinoma cells.
AB  - BACKGROUND: By using proteomic technology, the authors previously observed the
      substantial down-regulation of mammary serine protease inhibitor (maspin) in
      esophageal squamous cell carcinoma and metastases. In the current study, they
      examined the effects of maspin re-expression in a maspin-null esophageal cancer
      cell line EC109 and also investigated the underlying mechanism. METHODS: A cell
      line with stable maspin expression was established. An epithelial growth factor
      (EGF)-induced epithelial-mesenchymal transition (EMT) model was used to mimic
      some aspects of the metastatic process in vitro. The effects of maspin
      reintroduction on EGF-induced EMT and cell growth characteristics were evaluated.
      Comparative proteomic analysis of transfected cells versus parental cells was
      then performed to explore the potential mechanism. RESULTS: The introduction of
      maspin into EC109 cells was able to inhibit EGF-induced EMT and altered cell
      growth characteristics, including the serum dependence, proliferative response to
      EGF stimulation, and colony formation ability in soft agar, indicating a
      conversion from a malignant phenotype to a benign phenotype. Proteomic analysis
      revealed a significant down-regulation of a group of glycolytic enzymes in maspin
      transfected cells. In addition, maspin-transfected cells expressed much lower
      levels of hypoxia-inducible factor 1alpha than parental cells or empty vector
      transfected cells. CONCLUSIONS: Maspin exhibited a metastasis-suppressive effect,
      which may be a consequence of the reversal of the malignant phenotype of EC109
      cells. The switch of cellular metabolic phenotype to low glycolysis by the gain
      of maspin function may play a key role in the process. This finding provides
      additional evidence of the tumor metastasis-suppressive activity of maspin and
      may indicate a new direction for future studies of the mechanism of maspin.

PMID- 19090016
TI  - Fibril aggregation inhibitory activity of the beta-sheet breaker peptides: a
      molecular docking approach.
AB  - In the present study, we used a molecular docking as a rapid, interactive method
      to study the inhibition of fibrillogenesis process by beta-sheet breaker peptide
      (BSB) (Ac-L(1)-V(2)-(NMet)F(3)-F(4)-A(5)-NH(2)). Our aim was to find the complex
      (Abeta:BSB) that blocks the aggregation of the fibrils, and to identify the
      binding sequences for the small peptides on Abeta(1-42). An NMR structure solved
      by Luhrs et al. in 2005 was used to study the interaction of BSB with the amyloid
      aggregated forms. From our preliminary step-by-step docking studies, the L(17)
      D(23) sequence seems to be one of the most common active sites of Abeta(1-42),
      and critical in amyloid fibril formation. We note that a single molecule of BSB
      does not influence the interaction between the two fibrils, while a little excess
      of BSB (two molecules) with respect to the amyloid does not completely block but
      undoubtedly obstructs the aggregation process.

PMID- 19090017
TI  - A linear-time algorithm for predicting functional annotations from PPI networks.
AB  - Recent proteome-wide screening efforts have made available genome-wide, high
      throughput protein-protein interaction (PPI) maps for several model organisms.
      This has enabled the systematic analysis of PPI networks, which has become one of
      the primary challenges for the systems biology community. Here, we address the
      problem of predicting the functional classes of proteins (i.e. GO annotations)
      based solely on the structure of the PPI network. We present a maximum likelihood
      formulation of the problem and the corresponding learning and inference
      algorithms. The time complexity of both algorithms is linear in the size of the
      PPI network, and our experimental results show that their accuracy in functional
      prediction outperforms current existing methods.

PMID- 19090018
TI  - Mining overrepresented 3D patterns of secondary structures in proteins.
AB  - We consider the problem of finding overrepresented arrangements of secondary
      structure elements (SSEs) in a given dataset of representative protein
      structures. While most papers in the literature study the distribution of
      geometrical properties, in particular angles and distances, between pairs of
      interacting SSEs, in this paper we focus on the distribution of angles of all
      quartets of SSEs and on the extraction of overrepresented angular patterns. We
      propose a variant of the Apriori method that obtains overrepresented arrangements
      of quartets of SSEs by combining arrangements of triplets of SSEs. This specific
      case will pose the basis for a natural extension of the problem to any given
      number of SSEs. We analyze the results of our method on a dataset of 300
      nonredundant proteins. Supplementary material is available at
      (http://www.dei.unipd.it/nciompin/papers/CGZ-jbcb-suppl.pdf/).

PMID- 19090019
TI  - Visualizing microarray data for biomarker discovery by matrix reordering and
      replicator dynamics.
AB  - In most microarray data sets, there are often multiple sample classes, which are
      categorized into the normal or diseased type. Traditional feature selection
      methods consider multiple classes equally without paying attention to the
      upregulation/downregulation across the normal and diseased classes; while the
      specific gene selection methods for biomarker discovery particularly consider
      differential gene expressions across the normal and diseased classes, but ignore
      the existence of multiple classes. More importantly, there are few visualization
      algorithms to assist biomarker discovery from microarray data. In this paper, to
      help users visually analyze microarray data and improve biomarker discovery, we
      propose to employ matrix reordering techniques that have been developed and used
      in matrix computation. In particular, we generalized a well-known population
      genetic algorithm, namely, replicator dynamics, to reorder a microarray data
      matrix with multiple classes. The new algorithm simultaneously takes into account
      the global between-class data pattern and local within-class data pattern. Our
      results showed that our matrix reordering algorithm not only provides a
      visualization method to effectively analyze microarray data on both genes and
      samples, but also improves the accuracy of classifying the samples.

PMID- 19090020
TI  - An integrative domain-based approach to predicting protein-protein interactions.
AB  - Protein-protein interactions (PPIs) are intrinsic to almost all cellular
      processes. Different computational methods offer new chances to study PPIs. To
      predict PPIs, while the integrative methods use multiple data sources instead of
      a single source, the domain-based methods often use only protein domain features.
      Integration of both protein domain features and genomic/proteomic features from
      multiple databases can more effectively predict PPIs. Moreover, it allows
      discovering the reciprocal relationships between PPIs and biological features of
      their interacting partners. We developed a novel integrative domain-based method
      for predicting PPIs using inductive logic programming (ILP). Two principal domain
      features used were domain fusions and domain-domain interactions (DDIs). Various
      relevant features of proteins were exploited from five popular genomic and
      proteomic databases. By integrating these features, we constructed biologically
      significant ILP background knowledge of more than 278,000 ground facts. The
      experimental results through multiple 10-fold cross-validations demonstrated that
      our method predicts PPIs better than other computational methods in terms of
      typical performance measures. The proposed ILP framework can be applied to
      predict DDIs with high sensitivity and specificity. The induced ILP rules gave us
      many interesting, biologically reciprocal relationships among PPIs, protein
      domains, and PPI-related genomic/proteomic features. Supplementary material is
      available at (http://www.jaist.ac.jp/~s0560205/PPIandDDI/).

PMID- 19090021
TI  - Development of an affinity evaluation and prediction system by using the shape
      complementarity characteristic between proteins.
AB  - A system was developed to evaluate and predict the interaction between protein
      pairs by using the widely used shape complementarity search method as the
      algorithm for docking simulations between the proteins. This system, which we
      call the affinity evaluation and prediction (AEP) system, was used to evaluate
      the interaction between 20 protein pairs. The system first executes a "round
      robin" shape complementarity search of the target protein group, and evaluates
      the interaction of the complex structures obtained by shape complementarity
      search. These complex structures are selected by using a statistical procedure
      that we developed called "grouping". At a low prevalence of 5.0%, our AEP system
      predicted protein-protein interaction with 65.0% recall, 15.1% precision, 80.0%
      accuracy, and had an area under the curve (AUC) of 0.74. By optimizing the
      grouping process, our AEP system successfully predicted 13 protein pairs (among
      20 pairs) that were biologically significant combinations. Our ultimate goal is
      to construct an affinity database that will provide crucial information obtained
      using our AEP system to cell biologists and drug designers.

PMID- 19090022
TI  - Duplicated RNA genes in teleost fish genomes.
AB  - Teleost fishes share a duplication of their entire genomes. We report here on a
      computational survey of structured non-coding RNAs (ncRNAs) in teleost genomes,
      focusing on the fate of fish-specific duplicates. As in other metazoan groups, we
      find evidence of a large number (11,543) of structured RNAs, most of which (~86%)
      are clade-specific or evolve so fast that their tetrapod homologs cannot be
      detected. In surprising contrast to protein-coding genes, the fish-specific
      genome duplication did not lead to a large number of paralogous ncRNAs: only 188
      candidates, mostly microRNAs, appear in a larger copy number in teleosts than in
      tetrapods, suggesting that large-scale gene duplications do not play a major role
      in the expansion of the vertebrate ncRNA inventory.

PMID- 19090023
TI  - Haplotype inference and block partitioning in mixed population samples.
AB  - Multi-population haplotype inference and block partitioning is a difficult task
      when dealing with mixed genotype samples. A number of studies have shown that the
      haplotype block structures, as well as the collections of common haplotypes and
      their frequencies, vary significantly among world populations. These differences
      are more extreme when the geographical locations for the populations are more
      distant. Some of the previous studies performed haplotype inference in multi
      population samples with known population assignment. Others developed algorithms
      for clustering of the mixed haplotype or genotype samples with different block
      structures or genetic marker profiles. We present a new algorithm that performs
      haplotype inference and block partitioning in a mixed sample of genotypes from
      two populations when the population assignments are not known. Given a mixed
      genotype sample, the proposed algorithm (HAPLOCLUST) extracts two clusters of
      genotypes with different block structures in addition to performing haplotype
      inference on each of these clusters. When tested on a set of unrelated
      individuals, our algorithm provides correct assignments comparable to those of
      two state-of-the-art algorithms for population stratification. The contribution
      of HAPLOCLUST consists of performing haplotype/block-based population
      stratification and simultaneously finding the haplotype resolution and block
      partitioning for the extracted clusters.

PMID- 19090024
TI  - EnGenIUS -- Environmental Genome Informational Utility System.
AB  - Short-insert shotgun sequencing approaches have been applied in recent years to
      environmental genomic libraries. In the case of complex multispecies microbial
      communities, there can be many sequence reads that are not incorporated into
      assemblies, and thus need to be annotated and accessible as single reads. Most
      existing annotation systems and genome databases accommodate assembled genomes
      containing contiguous gene-encoding sequences. Thus, a solution is required that
      can work effectively with environmental genomic annotation information to
      facilitate data analysis. The Environmental Genome Informational Utility System
      (EnGenIUS) is a comprehensive environmental genome (metagenome) research toolset
      that was specifically designed to accommodate the needs of large (> 250 K
      sequence reads) environmental genome sequencing efforts. The core EnGenIUS
      modules consist of a set of UNIX scripts and PHP programs used for data
      preprocessing, an annotation pipeline with accompanying analysis tools, two
      entity relational databases, and a graphical user interface. The annotation
      pipeline has a modular structure and can be customized to best fit input data set
      properties. The integrated entity relational databases store raw data and
      annotation analysis results. Access to the underlying databases and services is
      facilitated through a web-based graphical user interface. Users have the ability
      to browse, upload, download, and analyze preprocessed data, based on diverse
      search criteria. The EnGenIUS toolset was successfully tested using the Alvinella
      pompejana epibiont environmental genome data set, which comprises more than 300 K
      sequence reads. A fully browsable EnGenIUS portal is available at
      (http://ocean.dbi.udel.edu/) (access code: "guest"). The scope of this paper
      covers the implementation details and technical aspects of the EnGenIUS toolset.

PMID- 19090025
TI  - Children's expressed emotions when disclosing maltreatment.
AB  - OBJECTIVE: Our goal was to examine children's expressed emotions when they
      disclose maltreatment. Little scientific research exists on this topic, and yet
      children's emotional expressions at disclosure may inform psychological theory
      and play a crucial role in legal determinations. METHOD: One hundred and twenty
      four videotaped forensic interviews were coded for children's emotional displays.
      In addition, children's trauma-related symptoms (depression, dissociation, and
      PTSD) and global adaptive functioning were assessed, and abuse type and frequency
      were documented. RESULTS: Most children in the sample evinced neutral emotion
      during disclosure. However, stronger negative reactions were linked to indices of
      psychopathology. Number of abuse experiences was inversely related to negative
      emotional displays. CONCLUSION: Fact finders may profit from knowing that
      maltreated children do not necessarily cry or display strong emotion when
      disclosing maltreatment experiences. Nevertheless, predictors of greater negative
      affect at disclosure can be identified: fewer abuse experiences; higher global
      adaptive functioning; and for sexually abused children, greater dissociative
      tendencies. PRACTICE IMPLICATIONS: Although further research is needed,
      practitioners should consider that children who disclose abuse may display
      relatively neutral affect despite having experienced maltreatment.

PMID- 19090026
TI  - De-novo 2.15 Mb terminal Xq duplication involving MECP2 but not L1CAM gene in a
      male patient with mental retardation.
AB  - Distal Xq disomy in males results in characteristic phenotypes that typically
      include mental retardation, microcephaly, prominent hypotonia and hypogonadism.
      The 8-year-old male patient reported here presented with mental retardation,
      prominent ears, abnormally wide and unstable gait and flat occiput. He did not
      have microcephaly or hypogonadism. Subtelomeric multi-fluorescence in-situ
      hybridization analysis identified a duplicated terminal portion of chromosome
      Xq/Yq located distally on Yp. Further analysis of the duplicated region using
      additional FISH probes, specific for the distal Xq and Yp chromosomal regions,
      and array comparative genomic hybridization analysis using the 244 K oligo-array
      of Agilent, showed that it spans approximately 2.15 Mb of the terminal Xq region
      and includes MECP2 but not L1CAM gene. This is the smallest well-characterized
      terminal Xq duplication reported to date. Genes proximal to MECP2 that are not
      duplicated in our patient are likely responsible for additional clinical
      manifestations including characteristic facial dysmorphic features, microcephaly,
      hypogonadism and more severe hypotonia, as noted in patients with larger distal
      Xq duplications. Our patient's features are similar to previously reported MECP2
      gene duplication cases, thus suggesting minor or no contribution of duplicated
      genes distal of MECP2 to the reported phenotype.

PMID- 19090027
TI  - The Democratic Republic of the Congo in crisis.

PMID- 19090028
TI  - Naming the problem: disorders and their meanings.

PMID- 19090029
TI  - Five-year risk of colorectal neoplasia after negative colonoscopy.

PMID- 19090030
TI  - Five-year risk of colorectal neoplasia after negative colonoscopy.

PMID- 19090031
TI  - Bortezomib plus melphalan and prednisone for multiple myeloma.

PMID- 19090032
TI  - Bortezomib plus melphalan and prednisone for multiple myeloma.

PMID- 19090033
TI  - [Influenza vaccination coverage in asthmatic children in  France in 2006-2007].
AB  - In France, an annual seasonal influenza vaccination has been recommended since
      2000 for patients suffering from chronic respiratory diseases, including asthma.
      Each year, a free influenza vaccination voucher is sent by the French Public
      Health Insurance authorities to patients with chronic respiratory disease,
      including severe asthma. In November 2006, this measure was extended to all
      asthmatic patients, irrespective of asthma severity. The present paper examines
      the 2006-2007 influenza vaccination coverage rate in 433 asthmatic children aged
      six to 17 years (mean age: 9.5 years; male: 61%) who consulted a pediatric
      pulmonologist between March and September 2007 in eight hospitals throughout
      France. The influenza vaccination coverage rate was 15.7% for the 2006-2007
      season (13.9% for the 2005-2006 season and 10.9% for the 2004-2005 season).
      General practitioners vaccinated 72.1% of the children. Lack of information (42%)
      was the most frequently reported reason for non-vaccination. Free vouchers
      (received by 39.6% of the children) significantly increased the vaccination
      coverage rate (31% versus 5.9%; p < 0.001). In France, in 2006-2007, the
      influenza vaccination coverage rate in asthmatic children was far below the
      national public health objective to achieve for the year 2008 (at least 75%).
      Concerted action is needed to improve the influenza vaccination coverage rate in
      asthmatic children.

PMID- 19090034
TI  - NHERF1 mutations and responsiveness of renal parathyroid hormone.

PMID- 19090035
TI  - Treatment-resistant depression.

PMID- 19090036
TI  - Review: vasomotor symptoms peak at 1 year after final menstrual period and may
      persist for many years.

PMID- 19090037
TI  - Acute cervical pain syndrome resulting from suppressed sneezing.

PMID- 19090038
TI  - Afcwh41 is required for cell wall synthesis, conidiation, and polarity in
      Aspergillus fumigatus.
AB  - alpha-Glucosidase I regulates trimming of the terminal alpha-1,2-glucose residue
      in the N-glycan-processing pathway, which plays an important role in the quality
      control system in mammalian cells. However, the consequence of glucose trimming
      of the N-glycan in filamentous fungi is unclear. We identified the gene encoding
      alpha-glucosidase I in the human opportunistic fungal pathogen Aspergillus
      fumigatus, namely Afcwh41. Deletion of the Afcwh41 gene resulted in a defective N
      glycan processing of the proteins secreted by A. fumigatus. Although the Afcwh41
      was not essential for hyphal growth and virulence, a severe reduction in conidia
      formation and a temperature-sensitive deficiency of cell wall integrity (CWI)
      were observed. Also, abnormalities of polar growth and septation were observed
      during conidial germination and hyphal elongation of the mutant. Our results
      suggest that Afcwh41 was involved in CWI, polarity, septation, and conidiation in
      A. fumigatus, probably by affecting the proper function of the proteins that are
      required for cell wall synthesis.

PMID- 19090039
TI  - Resistant hypertension needs special attention.  Changing medication, extra tests
      sometimes needed to control blood pressure.

PMID- 19090040
TI  - Wrist artery a safe approach to the heart.  Angioplasty via the radial artery in
      the arm is a good alternative to the approach via the groin.

PMID- 19090041
TI  - Beats per minute a signal of heart health.  Slowing your heart rate with exercise
      and stress reduction may help you enjoy more beats.

PMID- 19090043
TI  - Pre-dental antibiotics for few, not many.

PMID- 19090042
TI  - Folic acid: too much of a good thing?  As is true for many supplements, this
      vitamin may be a double-edged sword.

PMID- 19090044
TI  - New COPD medications seem okay for the heart.

PMID- 19090045
TI  - Ask the doctor.  A test showed that I have calcium in my aorta.  My doctor said
      it isn't serious, and that, as a 79-year-old, I will have to "live with it."  Can
      you tell me more about this condition?

PMID- 19090046
TI  - Rising rates of chronic health conditions: what can be done?
AB  - The growing prevalence of chronic health conditions--about 60 percent of the
      adult U.S. population had at least one chronic condition in 2005--has added costs
      to the U.S. health care system. Prevention and better management of chronic
      conditions are often cited as ways to improve health outcomes and slow U.S.
      health care spending growth--or at least generate better value for the $2.1
      trillion spent annually on health care in the United States. Yet, the health care
      system remains largely focused on acute, episodic care, according to experts at a
      Center for Studying Health System Change (HSC) conference titled, Rising Rates of
      Chronic Health Conditions: What Can Be Done? Panelists explored the role of
      obesity in rising rates of chronic conditions, the need for better information on
      how to treat patients with multiple chronic conditions, how to help patients
      improve self-management skills and how difficult changing unhealthy behaviors can
      be.

PMID- 19090047
TI  - Using private demand studies to calculate socially optimal vaccine subsidies in
      developing countries.
AB  - Although it is well known that vaccines against many infectious diseases confer
      positive economic externalities via indirect protection, analysts have typically
      ignored possible herd protection effects in policy analyses of vaccination
      programs. Despite a growing literature on the economic theory of vaccine
      externalities and several innovative mathematical modeling approaches, there have
      been almost no empirical applications. The first objective of the paper is to
      develop a transparent, accessible economic framework for assessing the private
      and social economic benefits of vaccination. We also describe how stated
      preference studies (for example, contingent valuation and choice modeling) can be
      useful sources of economic data for this analytic framework. We demonstrate
      socially optimal policies using a graphical approach, starting with a standard
      textbook depiction of Pigouvian subsidies applied to herd protection from
      vaccination programs. We also describe nonstandard depictions that highlight some
      counterintuitive implications of herd protection that we feel are not commonly
      understood in the applied policy literature. We illustrate the approach using
      economic and epidemiological data from two neighborhoods in Kolkata, India. We
      use recently published epidemiological data on the indirect effects of cholera
      vaccination in Matlab, Bangladesh (Ali et al., 2005) for fitting a simple
      mathematical model of how protection changes with vaccine coverage. We use new
      data on costs and private demand for cholera vaccines in Kolkata, India, and
      approximate the optimal Pigouvian subsidy. We find that if the optimal subsidy is
      unknown, selling vaccines at full marginal cost may, under some circumstances, be
      a preferable second-best option to providing them for free.

PMID- 19090048
TI  - Parental leave policies and parents' employment and leave-taking.
AB  - We describe trends in maternal employment and leave-taking after birth of a
      newborn and analyze the extent to which these behaviors are influenced by
      parental leave policies. Data are from the June Current Population Survey (CPS)
      Fertility Supplements, merged with other months of the CPS, and cover the period
      1987 to 1994. This time span is one during which parental leave legislation
      expanded at both the state and federal level. We also provide the first
      comprehensive examination of employment and leave-taking by fathers of infants.
      Our main finding is that leave expansions are associated with increased leave
      taking by both mothers and fathers. The magnitudes of the changes are small in
      absolute terms but large relative to the baseline for men and much greater for
      college-educated or married mothers than for their less-educated or single
      counterparts.

PMID- 19090049
TI  - The theory and practice of colour management: a guide for photographers, stoke-on
      trent, 9 July 2008.

PMID- 19090050
TI  - "Who is the captain of all these men of death?" the social structure of a
      tuberculosis sanatorium in postwar Germany.

PMID- 19090052
TI  - Sex and war in ancient Polynesia.

PMID- 19090053
TI  - From state-directed non-development and organized gender violence to transition
      in Vojvodina and Serbia.

PMID- 19090054
TI  - "Civilization" and its insecurities: traveling scientists, global science, and
      national progress in the Novosibirsk Akademgorodok.

PMID- 19090055
TI  - Cultural liminality and hybridity: the Romanian "transition.".

PMID- 19090056
TI  - Japanese women in science and technology.

PMID- 19090057
TI  - [The opposition between society and the state during the 1939-41 supply crisis].

PMID- 19090058
TI  - [From "hashish connoisseur" to drug addict: continuity and change in the
      sociology of drug users, 1916-39].

PMID- 19090061
TI  - On the front line: nurses urged to get influenza vaccination.

PMID- 19090062
TI  - Summary of violent deaths in Oklahoma.

PMID- 19090064
TI  - Understand your rights when a complaint is filed against your nursing license.

PMID- 19090063
TI  - The environment within us.

PMID- 19090065
TI  - Pay for performance: a nursing perspective.

PMID- 19090066
TI  - Should I stay or do I go now: eight ways to increase loyalty and retention.

PMID- 19090067
TI  - Physical activity guidelines for Americans.

PMID- 19090068
TI  - Full circle.

PMID- 19090069
TI  - The single-tooth dental implant restoration.

PMID- 19090070
TI  - Treatment planning for the single-tooth implant restoration--general
      considerations and the pretreatment evaluation.
AB  - This article reviews relevant clinical and radiographic information necessary to
      formulate an appropriate treatment plan for a patient requiring a single-tooth
      implant restoration. A step-by-step approach to collecting and analyzing this
      information a the pretreatment evaluation is presented. General considerations
      affecting implant treatment planning are discussed as are the parameters
      dictating ideal implant position and angulation.

PMID- 19090071
TI  - A multidisciplinary approach to treatment planning the single-implant
      restoration: interdisciplinary coordination.
AB  - The purpose of this article is to delineate the sequential thought process
      involved in a multidisciplinary approach to treatment planning the single-implant
      restoration. The pertinent issues involving orthodontic, surgical and restorative
      processes will be discussed comprehensively, with an emphasis on how
      communication and coordination among specialists influence the manner in which
      treatment is rendered.

PMID- 19090072
TI  - The peri-implant papilla: realities on papilla preservation and reformation.
AB  - The purpose of this article is to provide clinicians with an understanding of the
      biologic parameters influencing peri-implant papilla preservation and
      reformation. The article reviews peri-implant papilla reconstruction techniques
      with emphasis on presurgical bone and soft tissue biotype assessment. Hard tissue
      management via surgical and orthodontic procedures is also summarized. Finally,
      the article discusses important implant selection and positioning
      characteristics, soft tissue augmentation, and emergence profile considerations
      in the esthetic peri-implant zone.

PMID- 19090073
TI  - The single-tooth dental implant: practical guidelines for hard tissue
      augmentation.
AB  - With the increased popularity of implants and focus on .. esthetics, there is
      great emphasis on idealized bone foundation and soft tissue contours. The goal of
      reconstructive procedures is to provide peri-implant bone that support and
      maintain gingival contours. This article reviews ridge deficiency diagnosis and
      predicts the need for bone augmentation before tooth extraction. It also presents
      early intervention to minimize bone loss, various bone reconstruction techniques,
      and suggests predictable methods for different clinical scenarios.

PMID- 19090074
TI  - Stroke of luck.

PMID- 19090076
TI  - What has your facility done to prevent violence against nurses?

PMID- 19090075
TI  - Speaking out against workplace violence.

PMID- 19090077
TI  - Sell or design healthcare products.

PMID- 19090078
TI  - Teaching i.v. therapy to pediatric nurses. Specialized training programs
      alleviate pain for both patients and practitioners.

PMID- 19090079
TI  - ECT: a method to lift depression. controlled seizures refocus brain waves in
      severe depression.

PMID- 19090080
TI  - eICU: Big brother, great friend. Remote monitoring of patients is a boon for
      nurses, patients, and families.

PMID- 19090082
TI  - The many faces and many places of nursing.

PMID- 19090081
TI  - Strength training; not just for the young.

PMID- 19090083
TI  - A backpack and a mission: the journey of a missionary nurse.
AB  - A medical mission to a small village in Fiji brought improved health care to a
      community and an indelible change in a nurse's heart.

PMID- 19090084
TI  - Reflections on effective nursing partnerships addressing mental health in the
      Latino community.
AB  - An academic/community collaboration assesses attitudes about and knowledge of
      resources for mental health care in the Latino community and develops
      interventions and education/outreach models as well as ongoing partnerships.

PMID- 19090085
TI  - Out of the ordinary: nursing in Peru.
AB  - A high school friendship inspired a love of other cultures and a desire to pursue
      missionary nursing in South America. As a parish nurse in a remote village in
      Peru, the author trained village health workers in the basics of hygiene, first
      aid, and disease prevention.

PMID- 19090086
TI  - Nursing school: the extended version.
AB  - A nursing education is interrupted, reinforced, enhanced, and completed by
      service in the Minnesota Army National Guard.

PMID- 19090087
TI  - The clinical examiner role: an out-of-the-ordinary opportunity to help make a
      nurse.
AB  - A distinctive role in a pioneering nursing education model helps students fulfill
      in a nontraditional way their dreams of becoming registered nurses.

PMID- 19090088
TI  - Changing American nurses' perspectives of Turkish culture through travel and
      dialog.
AB  - A group of registered nurses in the graduate nursing program at Lubbock Christian
      University and their instructor traveled to Turkey in 2008 and, through personal
      contact and dialog, changed their perspectives about the country and its people.

PMID- 19090089
TI  - A sex offender therapist's story.
AB  - A therapist who works with sex offenders explains how she got involved in this
      work, what the treatment program entails, and the difficult homework the
      offenders must complete to graduate. She also describes the remodeling process
      offenders experience as they progress through treatment. Most of the offenders
      she has worked with are remorseful, have been victims themselves, work very hard
      in treatment, and make remarkable changes to become safe, productive members of
      society. That is why she has found this work to be some of the most challenging
      and rewarding work of her life.

PMID- 19090090
TI  - "The nurse in me" makes me a better lawyer.
AB  - An attorney who specializes in elder law discusses the value of her education as
      a nurse in providing legal services to her clients.

PMID- 19090091
TI  - Training traditional birth attendants in southern Sudan.
AB  - Traditional birth attendants are currently the principal service providers to
      pregnant women in southern Sudan. A training program provides education to
      promote maternal and newborn health as well as birth preparedness and establishes
      mechanisms for supportive supervision.

PMID- 19090092
TI  - CenteringPregnancy: group prenatal care.
AB  - A group model for providing prenatal care offers enhanced opportunities for
      patient education and interpersonal support. Research points to improved clinical
      outcomes as well as increased patient satisfaction.

PMID- 19090093
TI  - A call for change: perspectives on nurses' role in health care reform.
AB  - A new generation of nurse activists must follow in the footsteps of nursing
      pioneers such as Florence Nightingale and Lillian Wald to facilitate health care
      systems that promote healthy populations.

PMID- 19090095
TI  - Minnesota state senator Kathy Sheran, BSN, RN, MS.

PMID- 19090094
TI  - Defining nursing: a linguistic view.
AB  - A nurse who has practiced in different countries reflects on the words used in
      various languages to name our profession, and what those words have to say about
      the deeper meaning of nursing.

PMID- 19090096
TI  - Biological control of Faba bean pathogenic fungi by three cyanobacterial
      filtrates.
AB  - The aim of the present study is to evaluate the biological control aptitude of
      the cyanobacteria, Anabaena subcylindrica, Nostoc muscorum and Oscillatoria
      angusta filtrates on the growth of the isolated pathogenic fungi from the
      different organs of Faba bean. Three caynobacterial (Anabaena subcylindrica,
      Nostoc muscorum and Oscillatoria angusta) filtrates were prepared in different
      concentrations and their effects on the isolated pathogenic fungi from leaves,
      stems and roots of Faba bean were studied. The study revealed high efficiency of
      the three algal filtrates on the control of the isolated pathogenic fungi from
      the three organs of Faba bean plants. The reduction in fungal mat growth diameter
      was greater than in that of the fungal dry weight showing inhibited fungal spread
      by greater rate. The reduction in the fungal dry weight was mostly linear and
      significantly correlated with the algal filtrate concentrations. The Efficient
      Algal Filtrate Concentration (EAFC) ranged between 104 and 461% for the three
      algal filtrates on the studied fungi dry weight. Complete control of the isolated
      fungi could be achieved by of a mixture of two algal filtrates in their EAFC and
      that of Nostoc muscorum + Oscillatoria angusta filtrates with an EAFC 368 and
      194% were the best and economic mixture.

PMID- 19090097
TI  - Evaluation of operation of submerged aerated filters in wastewater treatment and
      excess sludge production.
AB  - The aims of this study were to evaluate the SCOD removal efficiency in submerged
      biological aerated filters (BAFs) and subsequently to assess the relationship
      between the specific surface area (Ss) and Excess Sludge Production (ESP) rate in
      such filters. Accordingly, four filters with different porosity and specific
      surface (647, 295, 175 and 136 m2 m(-3)) have been loaded with synthetic
      wastewater based on low fat dry milk powder with COD of 1500 mg L(-1) in
      different hydraulic retention time (8, 4, 2, 1 and 0.5 h). In this study, it was
      shown that specific surface increase of the filters initially increases the
      efficiency of the filters and after a certain value, the filter efficiency
      remains uncharged or decreases, as in HRT of 8 h the SCOD removal efficiency of
      filters 1 and 2 (Ss = 647 m2 m(-3) and Ss = 295 m2 m(-3)) were 89.8 and 91% at
      VOL of 3.195 and 3.727 kg COD m(-3) d(-1), respectively. Also, the results showed
      that in all the filters, the production rate of suspended sludge increases
      inversely with the hydraulic retention time and the media with higher porosity
      (90.5%) produced less suspended sludge (8-57 g m(-3)) despite having lower
      efficiency in the SCOD removal.

PMID- 19090098
TI  - Contribution to the geochemistry of trace elements in the sediments of the Noun
      River and tributaries, western Cameroon.
AB  - This study reports on the distribution of trace elements in the sediments of the
      Noun River valley. Two groups of trace elements have emerged based on their
      distribution and geochemical behaviour. The first group shows lower values
      whereas the second group aligns higher values. Elements like Al and Sr in one
      side and Zn, Zr in the other present concentrations statistically different from
      those of the rocks compared to other elements in trace analyzed (Cr, Ni, Ba, Co,
      Cu, Fe, Mn, V, As and Pb). The trace elements Al, Sr, Zr, Zn and Pb in the
      sediments of the Noun River show concentrations rather lower than those of the
      world. The average concentrations in elements C (3.72%), N (0.27%), S (0.05%) and
      of the ratios C/N (13.77) and N/S (5.29) reflect those resulting from the
      decomposition of the organic matter which derives from soils with very small
      concentrations in S. The Noun valley sediments are mostly of primary (quartz,
      microcline, plagioclase, orthoclase, ilmenite, anatase) and newly formed or
      secondary (kaolinite, gibbsite, hematite, goethite) minerals. This mineralogy and
      the overall low concentration of the studied trace elements, with Al, Fe, Ti and
      Mn as most abundant elements, is consistent with the local geology made up of the
      basic rocks (basalts, volcanic ash) and of the acid rocks (granites, gneiss).
      Overall the trace elements concentration and distribution suggest their geogene
      origin. Yet, this study is a first contribution of its kind towards the
      development of a baseline geochemical database essential for a sustainable and
      healthier Noun valley ecosystem.

PMID- 19090099
TI  - Characteristics and chemical composition of maleo-pimaric and fumaro-pimaric
      rosins made of Indonesian Pinus merkusii rosin.
AB  - This study was directed to look at the chemical composition of maleo-pimaric and
      fumaro-pimaric rosins made of unmodified rosin with maleic anhydride (MA) or
      fumaric acid (FA). The results showed that one peak of a maleopimaric acid (MPA)
      adduct on the chromatogram was obtained when a sample of this reaction product
      was injected into a Gas liquid chromatography (GLC) or Gas chromatograph-Mass
      spectrometer (GC-MS) system. Identification of this adduct using a GC-MS showed
      that a reaction product of rosin and MA produced endo-maleopimaric acid methyl
      ester. This peak of the adduct had a similar profile as in a previous study with
      a base peak at m/z =146 and prominent ions at m/z = 386, m/z = 187 and at m/z =
      121. In the making of MPA and fumaropimaric acid (FPA) adducts, the increase in
      molar ratio for both reaction temperatures of 125 and 2000C and all rosin samples
      used in the reaction process gave a higher yield of endo maleopimaric acid. The
      largest amount of this product was obtained at a molar ratio of 1:10 with the
      reaction at 200 degrees C. Among the origin of the rosin used in this experiment,
      rosin from Central Java produced the highest MPA, while the highest FPA was
      achieved by using rosin from North Sumatra. The relationship between the molar
      ratio and the concentration of MPA or FPA could be expressed as a quadratic
      equation. From the equation, one could predict the best molar ratio to produce
      the highest MPA or FPA adducts at a suitable molar ratio. Using the equation Y = 
      0.8475 X2 + 10.448X - 9.7125, at the reaction temperature 200 degrees C, the
      highest MPA (around 22.50%) could be achieved by using a molar ratio of rosin and
      MA of 1:6.2.

PMID- 19090100
TI  - Salicylic acid alleviates the cadmium toxicity in Chinese cabbages (Brassica
      chinensis).
AB  - To test the effects of Salicylic Acid (SA) on physiological changes of plants
      under cadmium stress one cultivar of Chinese cabbage (Brassica chinensis) cadmium
      resistance, Changkenxiaobaicai (tolerance) were studied with pots cultures. Like
      other organisms Plants have adaptatives mechanisms whereby they are able to
      respond to both nutrient deficiency and toxicities. Plants materials were
      originated from the vegetable market in Wuhan, Hubei China. The seeds were tested
      on the pot cultures in the green house. The results of our experiments were quite
      different between the treatments. The combined treatment Cd 5 ppm + SA 500 mmol
      L(-1) during our experiment showed that the activity of peroxidase and
      superoxidase dismutase in the cabbages were induced, the total chlorophyll
      content increased significally by 25.38%, chl a/b about 43.01% and total biomass
      about 41.67%, both in comparison with the control. The soluble sugar content
      increased significantly to about 25.47% in comparison with the control. The
      electrolyte leakages were less affected. Under SA treatment only, the chlorophyll
      content, chl a/b content increased to about 18.85%, in comparison with the
      control. Plant biomass increased about 18.90% with the addition of SA in the
      culture. SA treatment can increase or decrease the Chinese cabbages metabolism.
      Plants were exposed to 5 ppm CdCl2 for 5 days under natural light. Then they were
      cultivated with Hoagland nutrient solution, which served as control, nutrient
      solution supplemented with 5 ppm CdCl2. Five days after Cd treatment, seedlings
      were harvested. The experiment was performed in triplicate.

PMID- 19090102
TI  - Detection of cloned strR, an antibiotic regulatory gene, using RFLP and nested
      PCR.
AB  - The genetics of streptomycin production is well characterized in Streptomyces
      griseus. More than 25 clustered genes encode proteins involved in biosynthesis,
      regulation and transport functions. StrR, the pathway specific transcriptional
      activator or regulator that located in this cluster, then induces transcription
      of other streptomycin production genes by binding multiple sites in the gene
      cluster. We aim to put strR gene in to different multicopy and integrated
      expression vector specifically designed for Streptomyces. To start with, the
      isolated strR gene was ligated into pBluescript (pBs) vector and transformed into
      different strains of Escherichia coli. The correct structure of the recombinant
      plasmid, isolated from transformed E. coli, was confirmed using gel
      electrophoresis, PCR and double digested with restriction enzymes BamHI and
      EcoRI. Finally the plasmid map, named pFDstrR. This unique vector has a much
      expanded Multiple Cloning Site (MCS), which makes it suitable for different
      purposes of gene cloning and also site directed mutagenesis or gene targeting.
      This gene will be lifted up and transfer into different varieties of Streptomyces
      specific vectors in order to make different transgenic or genetically manipulated
      Streptomyces.

PMID- 19090101
TI  - An analysis on DNA fingerprints of thirty papaya cultivars (Carica papaya L.),
      grown in Thailand with the use of amplified fragment length polymorphisms
      technique.
AB  - The experiment was carried out at the Department of Horticulture, Ubon
      Ratchathani University, Ubon Ratchathani province, Northeast Thailand during June
      2002 to May 2003 aims to identify DNA fingerprints of thirty papaya cultivars
      with the use of Amplified Fragment Length Polymorphisms (AFLP) technique. Papaya
      cultivars were collected from six different research centers in Thailand. Papaya
      plants of each cultivar were grown under field conditions up to four months then
      leaf numbers 2 and 3 of each cultivar (counted from top) were chosen for DNA
      extraction and the samples were used for AFLP analysis. Out of 64 random primers
      being used, 55 pairs gave an increase in DNA bands but only 12 pairs of random
      primers were randomly chosen for the final analysis of the experiment. The
      results showed that AFLP markers gave Polymorphic Information Contents (PIC) of
      three ranges i.e., AFLP markers of 235 lied on a PIC range of 0.003-0.05, 47 for
      a PIC range of 0.15-0.20 and 12 for a PIC range of 0.35-0.40. The results on
      dendrogram cluster analysis revealed that the thirty papaya cultivars were
      classified into six groups i.e., (1) Kaeg Dum and Malador (2) Kaeg Nuan (3)
      Pakchong and Solo (4) Taiwan (5) Co Coa Hai Nan and (6) Sitong. Nevertheless, in
      spite of the six papaya groups all papaya cultivars were genetically related to
      each other where diversity among the cultivars was not significantly found.

PMID- 19090103
TI  - Effect of soil moisture stress on growth and yield of cassava in Nigeria.
AB  - Nine cassava genotypes were evaluated for their growth responses and adaptability
      to soil moisture stress on the field and in the screenhouse in Nigeria. Genotypes
      were evaluated in three savanna agroecologies in a randomized complete block
      design with three replicates. Screenhouse evaluation was conducted using three
      moisture regimes of 75, 50 and 25% Field Capacity (FC) in a two-factor factorial
      experiment in CRD with three replicates. Morphological and yield data were
      collected on the field and in the screenhouse. Results showed significant (p <
      0.05) difference among genotypes on the field and in the screenhouse. Field
      moisture stress led to a decline in plant height by 47%, stem girth by 15%,
      number of tubers by 95% and tuber yield by 87%. Screenhouse moisture condition of
      25% FC led to a reduction in plant height by 12.6 and 21.2%, stem girth by 16.3
      and 21.7%, number of roots by 94.5 and 88.7% and root weight by 93.3 and 94.9%,
      respectively at 16 and 30 WAP. Moisture stress therefore resulted into
      considerable reduction in both vegetative growth and yield of cassava genotypes.
      Therefore, a concerted effort in breeding cassava for drought tolerance is needed
      as cassava cultivation is expanding into nontraditional semiarid regions of sub
      Saharan Africa. Germplasm introduced from Latin America (especially north-eastern
      Brazil) is providing a unique source of variability to further broaden the
      genetic base for drought tolerance in cassava.

PMID- 19090104
TI  - Clinical and radiological findings following continent urinary diversion with
      colonic segment in dog.
AB  - In order to assess clinico-radiological findings of urinary diversion, five adult
      healthy mongrel dogs of both sexes weighing between 25-40 kg and average age of
      1.5 years, underwent continent urinary diversion surgery. In this approach
      fifteen centimeters of the descending colon with preservation of its mesenteric
      vessels was resected and this segment longitudinally was opened and flushed with
      an aqueous solution of povidin iodine 0.1% and the remaining colon re-anastomosed
      by seromuscular sutures. Then two ends of transected ureters were drawn into the
      resected colon by mosquito hemostatic forceps and simple interrupted sutures were
      placed between the ureter and the colonic mucosa for uretero-colonic anastomosis.
      The uretero-colonic part in a cap form transplanted to partially cystectomized
      bladder with one layer of cushing pattern suture. All animals survived after the
      operation. Clinically, all dogs were dull and depressed and passed blood tinged
      urine for first few postoperative days. There was pollakiuria in all of animals
      distinctly, but urinary incontinence was not observed. At the first few
      postoperative days, anorexia, nausea and vomiting were seen in three dogs. In all
      animals, polydipsia were seen and continued until the end of study. Intravenous
      urograms showed hydronephrosis and upper urinary tracts dilatation in all animals
      at 25th day but there were signs of improvement at 45th day distinctly.
      Unilateral ureteral obstruction was observed in two dogs. In regards to clinico
      radiological findings can be concluded that this operation has some distinct
      sequela that some of them may be seen in radiographic assessments.

PMID- 19090105
TI  - Surveying on the biologic behaviors of Hemiscorpius lepturus Peters 1861,
      scorpion in laboratory (Khuzestan, Iran) (Scorpions: Hemiscorpiidae).
AB  - This descriptive research was conducted so as to find and distinguish the sex of
      H. lepturus based on 107 dead specimens in the 70% ethyl alcohol and exact
      decision on their species using a criterion considering all morphological
      parameters and by the use of stereo microscope. Their biologic behaviors, 50 H.
      lepturus specimens which were fed and kept alive in capped bottles were studies
      while their way of shedding and number of newly-born young were also investigated
      under laboratory conditions in the process. The research revealed that in 107 H.
      lepturus specimens, 27 specimens (23%) were male and 80 ones (77%) were female.
      The results gained from 50 scorpions kept in the laboratory showed that only 10
      cases (20%) had shed. Duration of emergence varies in each young from 10-20 min
      and delivery lasts approximately for 4-6 h. The average number of the young born
      was 24.3 in each delivery. It was concluded that the time of delivery and
      shedding in H lepturus is definitely fixed during the year and the number
      ofpectine denticles and length of the tail can be used to differentiate male and
      female H. lepturus.

PMID- 19090106
TI  - The effects of three diets on some growth performance of whitefish (Coregonus
      lavaretus) fry.
AB  - In a 3 months experiment, the effects of three different kinds of food rations
      including culture rotifers, commercial food and the equal amount mixture of these
      two foods were studied on some growth specifications and survival of the
      whitefish (Coregonus lavaretus) fry. The initial average weight and length of the
      fry were 0.009 g and 4 mm, respectively. The period of experiment was among April
      to July 2003. The assessed characteristics variance analysis showed that the
      different food treatments caused very significant differences among the all
      averages (p < 0.01). Comparing the characteristics averages showed that during
      the first month of experiment, the best results of weight (0.029 g), total length
      (8.78 mm), specific growth rate (5.36%) and food efficiency (63.48%) were
      obtained in live food treatment, whereas the weakest averages of referred
      characteristics were observed in commercial food treatment. During the last month
      of experiment, some of the above results reversed so that the best averages of
      specific growth rate (3.73%) and food efficiency (44.3%) were observed in
      commercial food treatment. The results of this study showed that the use of
      rotifer as live food for fry has provided better survival rate than the other two
      treatments. However, this food could not provide the best results for the all
      measured characteristics in all of the experiment period, for the reason that
      during the third month of experiment period, using commercial food treatment
      which consist of more miscellaneous nutrient components, created better results
      for some fry's characteristics than the live food.

PMID- 19090107
TI  - Vitellogenin assay by enzyme-linked immunosorbant assay as a biomarker of
      endocrine disruptor chemicals pollution.
AB  - Research is ongoing to develop screening and testing programmes for endocrine
      disrupting effects of new chemicals and in the focus of this development are the
      fish test species common carp (Cyprinus carpio). In this study we have developed
      quantitative enzyme linked immunosorbent assays (ELISA) for VTS in common carp.
      The working range of the ELISA was 11.25 to 2000 ng mL(-1) (75-25% specific
      binding/maximum antibody binding [B/B0]) with a 50% B/B0 intra- and interassay
      variation of 3.9% (n=10) and 12.5% (n=30), respectively. This ELISA is capable of
      detecting VTG as low as 6 ng mL(-1) and can accurately detect VTG in even 10
      microL of plasma. The ELISA was applied to measurement of VTG production by male
      carp (Cyprinous carpio, Cyprinidae) fish exposure to ethynylestradiol. The
      results showed that the amount of VTG produced in plasma of exposed fish
      increased in logaritmic order comparing to the control group and the ELISA
      described here could be used as an indicator of water pollution to estrogenic
      pollutants.

PMID- 19090108
TI  - Effect of thymoquinone on malformations and oxidative stress-induced diabetic
      mice.
AB  - The present study was undertaken to investigate the effect of thymoquinone (THQ),
      an antioxidant and an active ingredient of Nigella sativa L. on embryonic
      development in streptozotocin (STZ)-induced diabetic mice. Female mice were
      divided into four groups, 10 each, as follows: (i) control group, (ii) mice
      treated with THQ alone (10 mg kg(-1) day(-1)), (iii) mice treated with STZ alone
      (45 mg kg(-1)), (iv) mice treated with STZ and THQ. Animals of all groups were
      killed by carbon dioxide inhalation, on day 19 of pregnancy. The fetuses were
      analyzed for their weight and malformations while malondialdehyde (MDA) and
      glutathione (GSH) concentrations were estimated in the maternal liver. The
      percentages of malformations and resorptions of fetuses in mice treated with STZ
      alone were 26.4 and 27.9%, respectively as compared to 1.8 and 2.5% observed in
      the control group. Mice receiving both STZ and THQ showed malformations and
      resorptions at 16.37 and 18.39%, respectively. The estimation of MDA and GSH were
      significantly decreased (p < 0.01) and increased (p < 0.05), respectively in the
      STZ and THQ group. The data of the present study demonstrate that the treatment
      of THQ during pregnancy of diabetic mice inhibits the rate of embryo
      malformations by reducing the free radicals, in addition to increasing the size
      and maturation of embryos. The results of the present investigation might suggest
      that the use of THQ is useful in pregnancy of diabetic females.

PMID- 19090109
TI  - Common forms of atresia in the ovary of some Red Sea fishes during reproductive
      cycle.
AB  - Four economic fish species were collected monthly from commercial catch land at
      El-Attaka fish landing (Saurida undosquamis, Rhabdosargus haffara,
      Nemipterusjaponicus and Liza carinata). Histoligical examination of ovaries of
      these species indicated the presence of atretic oocytes (oocyte retention) as a
      natural phenomenon in fishes. Depending on the histological descriptions atretic
      oocytes may be classified into two main types: a, bursting b, non bursting. In
      the present study, frequency of degenerating oocytes were affected by the gonad
      maturation. In the early stages, the frequency is very low. It increased
      gradually reaching its maximum in spent stage about 50%. There is a significant
      difference between the atretic oocytes and gonad maturation (p < 0.05). Atresia
      is also affected by the length of the spawning season (Long or short). All
      examined ovaries of multiple spawners (S. undosquamis) should atretic oocytes.
      But in (N. japonicus, R. haffara and L. carinata) about 30 to 35% of the ova show
      atresia. These species have limited spawning season.

PMID- 19090110
TI  - Effect of Azotobacter chroococcum application on quantity and quality forage of
      rapeseed cultivars.
AB  - The study was conducted to determine the effect of Azotobacter chroococcum
      (Azotobacter) application on quality and quantity forage of the rapeseed
      cultivars (RGS 003, Hyolla 401 and Hyolla 330) and the possibility of cultivation
      the rapeseed forage in summer. The experimental design was spilt plot laid out in
      randomized complete block with three replications. Different levels of
      Azotobacter (zero and one kg hal) and cultivars were randomized to main plot and
      sub plot units, respectively. Results showed that Azotobacter significantly
      affected on all quantity traits except plant height. There were significant
      differences among cultivars for dry matter, biomass, sub branch number, plant
      height and forage glucosinolate concentration. Therefore Azotobacter can be
      considered as growth promoting for rapeseed in the future studies. Also, RGS003
      cultivar was better than other cultivars when Azotobacter was applied.

PMID- 19090111
TI  - Inhibitory effect of koji Aspergillus terreus on alpha-glucosidase activity and
      postprandial hyperglycemia.
AB  - The compounds that could inhibit the activity of a-glucosidase are potentially
      used for antidiabetic by suppressing postprandial hyperglycemia. This research
      aimed to investigate the hypoglycemic activity in A. terreus koji extracted by
      ethyl acetate. The extracts was dissolved in methanol: water (1:4), followed by
      fractionations with n-hexane, methylene chloride and ethyl acetate. Each fraction
      was assayed for its activity against a-glucosidase. The active fraction was
      purified by column chromatography using silica gel and resin as adsorbent. The
      kopi extract showed potential as alpha-glucosidase inhibition with IC50 <10
      microg mL(-1) and showed combination of non-competitive and uncompetitive
      inhibition mode against a-glucosidase. Ethyl acetate fraction showed potential as
      inhibitor alpha-glucosidase with IC50 = 8.6 microg mL(-1). In animal experiment,
      active fraction (F10-4) of ethyl acetate fraction suppressed the increase of
      postprandial blood glucosidase level compare to the control. Thus it showed
      potential as alpha-glucosidase inhibitor and demonstrated depressed postprandial
      blood glucose level and may have potential use in the management of type 2
      diabetes.

PMID- 19090112
TI  - Effects of probiotics supplementation in daily milk intake of newborn calves on
      body weight gain, body height, diarrhea occurrence and health condition.
AB  - The effects of probiotic administration were studied in an experiment, using 120
      newborn calves. Calves were randomly assigned to two experimental groups (sixty
      calves for each group) and probiotic (0.25 g h(-1) day(-1)) was added in their
      daily milk intake until 90 days of age. After the first week, all calves
      (including control group) received starter ration containing 21.0% crude protein
      and 3.0% crude fat. Body weight gain, body height and general health condition of
      all calves were observed at day 30, 60 and 90. Also condition of feces was
      examined daily and the occurrence of diarrhea was recorded throughout the
      experiment. Mean values of weight gain during three successive months for
      treatment and control groups were 57.52 and 50.58 kg, respectively. Body weight
      gained was not significantly different for first and second mo between treatment
      and control groups (16.9 and 33.87 vs. 14.49 and 33.07 for fist and second months
      in treatment and control groups, respectively). However, these values were
      significantly different (p < 0.001) between treatment (57.52) and control (50.58)
      groups third months of age. Diarrhea was observed in 35 calves of control group,
      which was higher than 11 cases in calves treated with probiotic (p < 0.001). The
      body height values of control and treatment groups in three successive months
      were 5.49, 10.82 and 15.00 cm for control and 5.44, 9.25 and 15.75 cm for
      treatment groups in first, second and third mo, respectively, which showed no
      significant difference between two groups during this study. The results of this
      study indicated that present probiotic compound have beneficial effects,
      especially on the third month of age in rearing calves.

PMID- 19090113
TI  - Effect of integrated bombardment and Agrobacterium transformation system on
      transient GUS expression in hypocotyls of rapeseed (Brassica napus L. cv. PF704)
      microspore-derived embryos.
AB  - A new method for transformation of rapeseed microspore-derived embryos (MDEs),
      based on microwounding of MDEs by particle bombardment prior to inoculation with
      an Agrobacterium suspension was reported. In this study, effects of two
      transformation systems (integrated bombardment and Agrobacterium transformation
      system and the singular bombardment) on transient GUS expression in hypocotyls of
      rapeseed (Brassica napus L. cv. PF704) MDEs were studied. Bombardment parameters
      were: helium pressure, 1350 psi; distance between stopping screen and target
      tissue, 9 cm, gold particles size of 1.0 microm and chamber vacuum pressure, 24
      in Hg. In integrated system A. tumefaciens strain AGL1 carrying the binary vector
      pCAMBIA3301 was used. Bombarded hypocotyls of MDEs were inoculated with
      Agrobacteria at OD600 = 1.0 for 10 min or OD600 = 0.25 for 24 h. Integrated
      transformation system increased the mean number of blue spots about 2-2.5 fold
      compared to singular bombardment and inoculated hypocotyls with OD600 = 1.0 for
      10 min produced the highest number of blue spots per bombardment (743 +/- 23.67).

PMID- 19090115
TI  - Current distribution and status of Himalayan ibex in upper Neelum Valley,
      District Neelum Azad Jammu and Kashmir, Pakistan.
AB  - Nine months field survey was conducted from July 2004 to August 2005 to take the
      data on the distribution and population status of Himalayan ibex (Capra ibex
      sibirica) in the upper Neelum valley of Azad Kashmir. Survey was carried out
      using direct (senses) as well as indirect (sampling) methods. 122 animals of
      different categories were recorded in the study area. Total average population
      was composed of 31.79% male, 32.79% female, 25.41% young and 9.84% yearling
      animals. Various threats to the population of ibex in the area were also studied.

PMID- 19090114
TI  - Alkaline phosphatase and CD34 reaction of deciduous teeth pulp stem cells.
AB  - Endothelial progenitor cells from the pulp of milk teeth were isolated for use in
      clinical applications and tissue engineering. Normal deciduous teeth from
      children of 7 to 8 years of age, which more than half the tooth root was
      extracted, were selected from the dental centre. Cells from enzyme treated pulps
      were cultured and cells resulting from the fifth and eight subculture were
      combined for cell surface marker determination experiments. Cells were positive
      for CD34 marker with a total of 99/45%, determined by flowcytometry. Cells also
      demonstrated alkaline phosphatase (ALP) activity. From the developmental point of
      view, stem cells from the dental pulp seem to have derived from the neural crest,
      which our findings technically support this theory. In essence mobile progenitor
      cells from bone marrow of endothelial origin could also play a significant role
      in the derivation of dental pulp stem cells.

PMID- 19090116
TI  - Denaturation of Bacillus amyloliquefaciens alpha-amylase with urea.
AB  - The urea induced denaturation of the Bacillus amyoliqefaciens alpha-amylase (E.C.
      3.2.1.1) was studied by absorption measurements in the near ultra-violet region
      and specific activity measurements. Spectral measurements were made at pH 6.9 and
      over the temperature range 20-80 degrees C. It has been observed that urea
      induced a cooperative transition. In the absence of denaturant, the Gibs energy
      changes were in the range of 8-15 kcal mol(-1). alpha-amylase lost 80% of its
      activity in the concentrated solution of urea. alpha-amylase was more
      thermostable than other mesophilic enzymes.

PMID- 19090117
TI  - Reproductive toxic effects of Artemisia herba alba ingestion in female Spague
      Dawley rats.
AB  - The objectives of this study is to investigate the toxic effects of Artemisia
      herba Alba (300 mg/kg/ body wight) on the reproductive system after
      administration to female Sprague-Dawley rats weighting 250-300 g for two time
      periods 4 and 12 weeks. Twenty adult female rats were divided into two groups and
      exposed to Topiramate diet at a concentration of 300 mg/kg/body weight for two
      periods of time. First group containing 10 rats received treatment for 4 weeks
      and a second group of 10 rats received the same dose of treatment for a period of
      12 weeks and compared with twenty non-exposed female rats received vehicle
      treatment. Female rats were allowed mating with males after 10 days prior to the
      last administration dose. Animals were autopsied under light anesthesia after
      mating and several parameters were determined including: Number of pregnant rats,
      body and reproductive organ weight, number of implantation sites, viable fetuses
      and resorption sites. Assessment of pregnancies in females was measured and the
      significance of these results was calculated using student's t and Chi-square
      tests. The effect of Artemisia herba alba exposure on fertility was assessed in
      terms of pregnant rats number, implantation sites, viable fetuses and resorption
      sites. Exposure to Artemisia herba alba for 4 weeks did not have much effect on
      fertility. Significant decrease in the relative ovarian weights and embryo
      weights in rats exposed to Artemisia herba alba were observed. Exposure to
      Artemisia herba alba for a 12 weeks resulted in a reduction in the percentage of
      pregnancies and in the number of implantation sites when compared with controls
      in both treatment periods. Rats receiving 12 weeks treatment showed an increase
      in ovarian weights and a decrease in viable fetus's number. These results
      indicate that long-term exposure of female rats to Artemisia herba Alba causes
      adverse effects on the reproductive system and fertility. The results of the
      current study suggest that ingestion of Artemisia herba alba by adult female rats
      causes adverse effects on fertility and reproduction.

PMID- 19090118
TI  - The effect of different concentrations of salicylic acid on protective enzyme
      activities of pepper (Capsicum annuum L.) plants.
AB  - The objective of this study was to investigate the effects of different
      concentration (0, 0.1, 0.7, 1.5, 3, 6 and 9 mM) of SA on antioxidant enzymes in
      Capsicum annuum L. plants. Enzyme activities of peroxidase, polyphenol oxidase,
      ascorbate peroxidase, catalase and glutathione reductase were measured. The
      plants were grown in pots vermiculite. Before applying the salicylic acid
      treatments, plants filled with were irrigated with based nutrient solution
      (Hoagland solution) for 5 weeks. After 5 weeks, plants were sprayed with
      different concentrations (0, 0.1, 1.5, 3, 6 and 9 mM) of salicylic acid. Data
      were analyzed using SPSS software and means were compared by Duncan test. In each
      experiment 4 replicats were used. Concentrations of 1.5, 3, 6 and 9 mM of SA
      caused significant increase in polyphenol oxidase and peroxidase enzyme
      activities in treated leaves. Concentrations of 0.7, 1.5 ad 3 mM of SA decreased
      in (catalase, ascorbate peroxidase and glutathione reductase) activities, but
      concentrations of 6 and 9 Mm of SA increased enzyme activities. Different
      concentrations of salicylic acid had different effects on enzyme activities in
      Capsicum annuum L.

PMID- 19090119
TI  - Description of Selenoportax vexillarius molars from Dhok Pathan Village (Middle
      Siwaliks), Pakistan.
AB  - Four molars of Selenoportax vexillarius are collected from village Dhok Pathan of
      the Middle Siwaliks. Out of four, two belong to upper dentition and the rest of
      two belong to lower dentition. The enamel plications vary owing to the ecological
      conditions and this feature can not be used for the comparison. The median basal
      pillars and median ribs are well developed in the molars and the comparative
      study is made with the type specimens of the species. The third molar of the
      species is broken anteriorly.

PMID- 19090120
TI  - Physicochemical studies on Uburu Salt Lake Ebonyi State-Nigeria.
AB  - Physicochemical properties of soil (sediment) and water from Uburu salt lake were
      evaluated and compared with control soil and surface water from the same
      community. Results showed significant (p < 0.05) higher values for the heavy
      metals cadmium, chromium, copper, lead and zinc in the lake water relative to the
      control. The values of these metals in the lake soil (sediments) however, were
      significantly (p < 0.05) lower than the control soil. Similar significant (p <
      0.05) elevations were observed in the lake water temperature, salinity, pH,
      calcium, magnesium, sodium, potassium, nitrate, carbonate, sulphate and phosphate
      levels compared to the control. Significant (p < 0.05) changes were also noted in
      the lake soil's pH, exchangeable acidity, nitrogen, organic carbon, calcium and
      magnesium levels. Also the soil texture was affected relative to the control. In
      a number of cases, the values of the studied parameters were higher than the
      permissible WHO standards. In view of these findings, cautious use of the salt
      lake soil and water is advocated.

PMID- 19090121
TI  - Endocrine disrupting chemicals in pesticides and herbicide in Fars Province,
      Iran.
AB  - Recent studies have shown that certain man-made compounds (including some
      pesticides and herbicide) through interfering with endocrine system, have the
      capability to induce developmental and reproductive abnormalities in humans and
      animals. Pesticides are currently being used in large scales in many developed
      and developing countries (including Iran), so this study has been conducted to
      determine the percentage of endocrine disruptor agents in pesticides used in Fars
      province. The results showed that more than 1,581,690 L of pesticides, in 86
      different brands, have been used in Fars province during year 1380 and 25.93% (34
      types) of them had at least one carcinogenic agents. At least 30 pesticides
      (711720 L, 44.99%) had one endocrine disruptor agent and therefore can be
      classified as environmental hormones or endocrine disrupting chemicals. The
      percentage of pesticides whom interfering with normal endocrine system activity
      were, 7.82% (66572 L), 4.54% (39975 L), 22.02% (348400 L), 5.12% (81000 L) and
      21.18% (34500 L) of pesticides were antiestrogenic, antiandorgenic, antityroidic,
      antigonadotropin and anitestroid hormones, respectively. The results showed that
      about 50% of pesticides which currently being used in Fars province should be
      banned.

PMID- 19090122
TI  - Some biological features of cotton whitefly, Bemisia tabaci (Homoptera:
      Aleyrodidae) on various host plants.
AB  - Development and reproduction of the cotton whitefly, Bemisia tabaci (Gennadius)
      were studied on aubergine, tomato and potato under laboratory conditions (30
      degrees C and 55% RH). Total life cycle from egg to adult was 14.9, 20.0 and 14.2
      days on aubergine, tomato and potato, respectively. Immature mortality were 12.9,
      18.1 and 12.3% at the same three host plants. Females of B. tabaci oviposited
      means of 51.8, 60.1 and 67.5 eggs on aubergine, tomato and potato, respectively
      and had a mean longevity of 8, 14 and 12.9 days on the same three host plants.
      The net reproductive rate was 18.12, 15.06 and 27.63 and the daily intrinsic rate
      of increase was 0.141, 0.092 and 0.165 on aubergine, tomato and potato,
      respectively.

PMID- 19090123
TI  - Population growth of the Venerid bivalve Circenita callipyga in the Hendijan
      Coast, Persian Gulf.
AB  - Length-frequency and growth of dominant species, Circenita callipyga (Bivalve,
      Veneridae) in the Hendijan coast, Khuzestan province (Persian Gulf) were studied
      from summer 2005 to spring 2006. Sampling was done seasonally with vanveen grab
      from 5 stations. Stations were located 0.5 mile apart and samples were collected
      from approximately 8 m depth. The population structure presented a size range
      between 0.5 and 9.5 mm length, being mainly formed by individuals from 3 to 4 mm,
      that were dominant in autumn. Recruitment rate was low and the major contribution
      of recruits was found in winter to spring. Growth parameters of the Von
      Bertalanffy growth function were estimated to be Linfinity = 25.06 mm, k = 0.180
      year(-1), t0 = 0.11 year.

PMID- 19090124
TI  - 6-aminopenicillanic acid production by intact cells of E. coli containing
      penicillin G acylase (PGA).
AB  - The aim of present study was to optimize conditions for conversion of penicillin
      G into 6-APA using intact crude cells of locally collected PGA producing
      bacterial strains as biocatalyst. Corn steep liquor medium supplemented with
      phenylacetic acid was used for PGA production. For enzymatic conversion of
      penicillin G into 6-APA by PGA impregnated bacterial cells, a maximum reaction
      time of 4 h was found adequate. The procedure for extraction and crystallization
      of 6-APA from the enzyme reaction mixture was standardized. Isolation process was
      carried out under controlled pH conditions and 6-APA crystals were recovered from
      the reaction mixture via filtration, concentration and drying. The maximum PGA
      activity was observed in Escherichia coli strain BDCS-N-FMu12 (6.4 mg 6-APA h(-1)
      mg(-1) wet cells) whereas Bacillus megaterium (ATCC 14945 used as check)
      exhibited only 2.4 mg 6-APA h(-1) mg(-1) wet cells. The overall yield of 6-APA
      crystals obtained after enzymatic conversion of penicillin G ranged between 37-55
      and 47-68% in foreign and local strains, respectively. BDCS-N-FMu12 was
      identified as the best PGA producer with 68% 6-APA conversion whereas ATCC 14945
      showed the lowest conversion (37%). The recovery of 6-APA (68%) obtained by using
      crude intact cells as cheap biocatalyst appeared promising. The process of enzyme
      fermentation and 6-APA crystallization optimized during this study seems cost
      effective and environment-friendly. However, further studies are required to
      scale up the 6-APA biosynthesis reaction for achieving 80-90% conversion of
      penicillin G into 6-APA by PGA hyper-producing locally collected strains of E.
      coli.

PMID- 19090125
TI  - Study on variation of potato varieties using electrophoretic tuber storage
      proteins.
AB  - Storage protein banding patterns of 13 varieties of potato (Solanum tuberosum L.)
      were compared by sodium dodecylsulfate polyacrylamide gel electrophoresis (SDS
      PAGE). Certain bands could be easily used by researchers to identify varieties
      under study or their hybrids. Tuber of potatoes that formed in farm were used as
      the source of plant materials. SDS-PAGE gave 30 protein bands in the 6.5-205 kDa
      molecular weight range, including 4 major bands (A, B, C, D), 11 prominent bands
      and 15 minor bands. Three major bands B, C and D at 23 to 25 kDa positions could
      be probably the isomers of the storage proteins, sporamin. Another thick band (A)
      at 40 kDa position was identified as patatin. Both sporamin and patatin appeared
      to be useful indicators of the percentage of protein present in a cultivar.
      Protein profiles were used to estimate the genetic distance among the varieties.
      They were clustered together between around 0.16 to 0.52 level of distance, with
      a mean value of 0.34, showing that the genetic dissimilarity between potato
      varieties is smaller than their similarity (1-0.34 = 0.66). Cluster analysis
      differentiated 13 varieties in 4 groups: (1) Fina (2) Bolesta, Marifona, Diamant
      and Bright (3) Agria, Cosmos, Herta, Romano Kondor and Ditta (4) Santi and
      Picasso. Romano and Kondor varieties were the most similar but the most
      dissimilar one was Finna.

PMID- 19090126
TI  - Effects of tiamulin, neomycin, tetracycline, fluorophenicol, penicillin G, Linco
      Spectin, erythromycin and oxytetracycline on controlling bacterial contaminations
      of the river buffalo (Buballus bubalis) semen.
AB  - In order to investigate the effects of tiamulin, neomycin, tetracycline,
      fluorophenicol, penicillin G, Linco-Spectin (0.15 mg mL(-1) lincomycin + 0.3 mg
      mL(-1) spectinomycin), erythromycin and oxytetracycline on controlling bacterial
      contaminations of the river buffalo semen, 120 mL diluted buffalo bull semen
      (diluted by tris-egg yolk extender) was divided into 5 mL tubes after initial
      evaluation and before (control sample) and at 0, 2, 6, 12 and 24 h after adding
      each of the above antibiotics at the recommended dose (D) and twice the
      recommended dose (Dx2) to the semen samples, each sample was cultured 4 times on
      Muller-Hinton agar medium and the results were recorded after 18 h incubation at
      37 degrees C. Tiamulin, tetracycline, neomycin and fluorophenicol were
      ineffective. Oxytetracycline was effective in both D and Dx2 (p < 0.001).
      Penicillin G in both D and Dx2 was effective (p < 0.001). Linco-Spectin was
      effective, though not significant, in D at 2 h and in Dx2 at 0 h only.
      Erythromycin in D was not significantly effective, but, in Dx2 was effective (p <
      0.001). Duration of the antibiotic exposure had no significant effect on the
      antibiotic potentials except for Linco-Spectin at 2 h (p < 0.014). The
      biochemical tests identified the contaminant bacteria as being a member of
      Arcanobacter (Corynebacterium) sp. In the next step, the semen sample of the same
      bull was taken, semen quality tests were carried out and the semen was diluted
      with the same extender (tris-egg yolk) + 7% glycerol, containing a double dose
      (Dx2) of these antibiotics and semen quality tests were carried out immediately
      after dilution, 18 h after storage at 4 degrees C and after the semen was packed
      in the straws, frozen in liquid nitrogen (-196 degrees C) and later thawed in 37
      degrees C water bath to investigate whether these antibiotics have any adverse
      effect on the spermatozoa during the process of freezing and thawing. The
      comparison of the results with those of the control group (the sample undergone
      the same process without adding antibiotics) indicated that oxytetracycline
      adversely affected sperm motility at 0 and 18 h, all the antibiotics had a lower
      percentage of sperm abnormal morphology than the control at 0 and 18 h, except
      for Linco-Spectin at 18 h and after freezing-thawing and tetracycline after
      freezing and thawing the sample which were the same as the control. Sperm
      viability was not affected by antibiotics before and after freezing. It was
      concluded that oxytetracycline and penicillin G in both D and Dx2 were effective
      in controlling seminal bacterial contaminations and because of the adverse effect
      of oxytetracycline on the sperm motility and morphology, it proved not to be
      suitable for this purpose but penicillin G could be recommended as an additive to
      the semen extenders.

PMID- 19090127
TI  - Effect of planting density on agronomical characteristics of rice (Oryza sativa
      L.) varieties in north of Iran.
AB  - In order to study the effects of plant density on agronomical characteristics of
      rice varieties a field experiment was carried out in field of Ghaemshahr Azad
      University in 2006. This experiment was laid out in split plot in basis of
      Randomized Completely Block Design with three replications. Main factor was rice
      variety in three levels (Hashemi Tarom, Fajr, Neda) and minor factor was planting
      density (Including 10 x 8.3, 10 x 10, 12.5 x 10, 16.6 x 10, 16.6 x 15 and 25 x 20
      cm or 120, 100, 80, 60, 40 and 20 plant m(-2), respectively). Results showed that
      planting density had significant effect on plant height, total spikelets, total
      tillers, fertile tillers, panicle per m2, grain yield and harvest index. Days
      number till to 50% flowering stage and growth period length were maximum in Neda
      variety. Also these characteristics were not influenced by different planting
      densities. Maximum plant height and maximum panicle length were obtained in
      Hashemi Tarom variety and minimum of these characteristics were produced in Neda
      variety. Plant height was decreased significantly with increase of planting
      density.

PMID- 19090128
TI  - Preliminary survey of edaphic algae in Al-Hasa region, Saudi Arabia.
AB  - Five soil samples were taken from different cultivated sites from the North
      Villages of Al-Hasa. Three algal groups were recorded throughout this study,
      Bacillariophyta, Cyanophyta and Chlorophyta. Fifty-two genera of algae were
      identified in all the soils sampled during this investigation. Out of these, 11
      genera belonged to the Chlorophyta; 16 genera belong to Bacillariophyta and 25
      genera to Cyanophyta. Penniate Bacillariophyta (Nitzschia, Gyrosigma),
      oscillatorid Cyanophyta (Osillatoria, Phormidium, Nostoc and Anabaena) and
      coccoid Chlorophyta (Ankistrodesmus falacatus, Chlorella ellipsoidea, Chlorella
      vulgaris, Gleocystis bcillus, Scenedesmus acuminatus, Scenedesmus arvensis and
      Scenedesmus bijuga) were the predominant in all investigated sites.

PMID- 19090129
TI  - Genetic trend in economic traits in Iranian native fowl.
AB  - Genetic parameters were estimated in base population of a closed experimental
      strain fowl, from data issued from 13 successive generations of selection. This
      population had been selected for body weight at 12 weeks of age (BW12) and egg
      number during the first 12 weeks of laying period (EN), mean egg weight at 28th,
      30th, 32nd weeks and Age at Sexual Maturity (ASM). Data were obtained on 35461
      Iranian native hens belonging to breeding center for Fars province in Iran. The
      method of multi-traits restricted maximum likelihood with an animal model was
      used to estimate genetic parameters. Resulting heritabilities for BW12, EN, EW
      and ASM were 0.58, 0.34, 0.62 and 0.49, respectively. Genetic correlations
      between BW12 and EN, EW and ASM were -0.06, 0.49 and 0.02, respectively. Genetic
      correlations between EN and EW and ASM were -0.26 and-0.77, respectively, while
      between EW and ASM, it was 0.20. The overall predicted genetic gains, after 13
      generations of selection, estimated by the regression coefficients of the
      breeding value on generation number were equal to 9.55, 0.99, 0.05 and -1.66, for
      BW12, EN, EW and ASM, respectively.

PMID- 19090130
TI  - Developmental time and fecundity of white peach scale, Pseudaulacaspis pentagona
      (Targioni-Tozzetti) (Homoptera: Diaspididae), on potato, kiwi and mulberry hosts
      in Iran.
AB  - The white peach scale (WPS), Pseudaulacaspis pentagona (Targioni-Tozzetti)
      (Homoptera: Diaspididae), is a world wide polyphagous scale insect. It is widely
      distributed in north of Iran, near the Caspian Sea areas, where it is the main
      pest of mulberry and kiwi trees. The development and fecundity of P. pentagona
      were examined at different temperatures and on different hosts in the laboratory.
      The longevity of WPS decreased with a rise in temperature. At 25 degrees C the
      largest number of crawlers (76.1 crawlers/female) was observed. The development
      time of WPS was generally longer on kiwi than mulberry or potato; fecundity was
      higher on potato than on other hosts, potato tubers and kiwi trees.

PMID- 19090131
TI  - A study of tannic acid degradation by soil bacteria.
AB  - A tannin-degrading strain of Bacillus sp. AB1 was isolated from a garden soil by
      enrichment. This organism was able to utilize 1% (w/v) tannic acid-a gallotannin
      at 30 degrees C and pH below 4.5 in a defined mineral medium where the acid was
      the sole source of carbon and energy under 96 h. Growth resulted in increase in
      OD concomitant with gradual decrease in pH of the culture medium. Analysis of the
      culture fluid by paper chromatography revealed glucose and gallic acid as major
      metabolites of tannic acid degradative pathway. Mineralization of tannic acid was
      informed when none of the metabolites was recovered after 96 h of incubation. The
      degradation potential of this isolate could be exploited for the production of
      tannase, improvement of livestock production and also detoxification of tannery
      effluents at extreme acidic conditions.

PMID- 19090132
TI  - Seroprevalence of antibodies to Toxoplasma gondii in sheep in center of Iran.
AB  - To provide an epidemiologic investigation of the seroprevalence of antibodies to
      Toxoplasma gondii in sheep population in Chaharmhal and Bakhtiari province (Iran)
      this study was conducted, the province containing five townships, (Shahrekord,
      Borujen, Farsan, Ardal and Lordegan). One thousands serum samples (600 female and
      400 male) were examined to detect antibodies to T. gondii by Indirect Fluorescent
      Antibody Test (IFAT). Serological results showed that the seroprevalence of
      antibodies to T. gondii was 29.1%. The seroprevalence in the townships were 38,
      22.5, 32, 35 and 18%, respectively. The results of titration of positive samples
      showed the following titers: 11% with 1/20, 9.3% with 1/40, 15.1% with 1/80,
      28.9% with 1/160 and 35.7% with/320 or more. There was no significant difference
      between the two sexes, while there was a significant difference between the
      townships located in east and west of the province.

PMID- 19090133
TI  - Effects of the extracts of Pycanthus angolensis against chemically induced acute
      hepatotoxicity.
AB  - The efficacy of the extract of Pycnanthus Angolensis (PA) against Carbon Tetra
      chloride (CCl4) induced hepatotoxicity was studied in rat. The study highlights
      information on the protective effect of PA extract as ethnomedical treatment of
      induced hepatotoxic injury. The dried powder of PA extract was administered
      orally at a dose of 300 mg/3 mL solution while liver injury was induced by carbon
      tetrachloride administered intraperitoneally at a dose of 0.67 mg kg(-1).
      Estimating the protein concentrations, saponins, alkaloid, glutathione and
      cholesterol levels monitored the hepato-protective activity. The result shows
      evidence of non-toxic response of PA extract against chemically induced hepatic
      damage. The antioxidant activities in the extract indicated its ability to
      protect against CCl4 induced hepatic injury in rat. The saponins and bile acids
      may have interacted with cholesterol in the liver to form unabsorbed complexes,
      which are excreted via faeces resulting in decrease level of cholesterol in the
      experimental animals.

PMID- 19090134
TI  - The effect of different sowing times on development and efficiency of some
      broccoli varieties grown in Corlu conditions.
AB  - This research has been conducted in Corlu which has a harder climate than its
      Province, Tekirdag where a similar research had done before, in order to study
      the effect of different sowing times on development and efficiency of some
      broccoli varieties. In the study realized in 2000: 4 varieties V1 (Shogun F1), V2
      (Pirate F1), V3 (Sultan F1) and V4 (Marathon F1) and 3 sowing times as July,
      August and September were used. While plant varieties and properties were not
      being effective, the sowing times were effective in the research. The average
      primary shoot weights of the varieties changed between 68.21-526.11 g; the
      average secondary shoot weights were between 8.90-30.82 g and the average
      secondary shoot was between 2.65-35.50 unit plant(-1). The average total plant
      values of the varieties per plant were determined as; with 68.34-550.17 g of
      efficiency values V3 (Sultan F1), V1 (Shogun F1), V4 (Marathon F1) and V2 (Pirate
      F1) are the most convenient varieties for Corlu Region respectively and
      relatively July, August and September are the most appropriate sowing times.

PMID- 19090135
TI  - RAPD markers associated with drought tolerance in bread wheat (Triticum aestivum
      L.).
AB  - Randomly Amplified Polymorphic DNAs (RAPDs) were used to search genetic diversity
      and markers associated with drought tolerance in 20 bread wheat cultivars. These
      cultivars are extensively being used by farmers in Iran, 6 of them are known as
      drought tolerant. Initial screens involved growing 10 cultivars at seedling stage
      under drought conditions (-5 and -8 bar) exerted by PEG 6000 in a hydroponic
      experiment. These tests confirmed the tolerance of the 6 above mentioned
      cultivars. Thirty 10-mer RAPD primers were used for fingerprinting of the
      cultivars of which primers P6 (TCGGCGGTTC) and P7 (CTGCATCGTG) produced
      respectively a 920 and a 750 bp band present in drought tolerant (absent in
      others) cultivars. These bands may be associated with drought tolerance in bread
      wheat.

PMID- 19090136
TI  - Effects of the fruit of Telfairia occidentalis on some biomolecules in rat.
AB  - The effects of the ethanolic fruit extract of T. occidentalis on some enzymes and
      biochemical parameters were evaluated in rats. 100, 500 and 1000 mg kg(-1) of the
      extract were administered orally and once daily to three different groups of
      rats, respectively, for 28 days. The fourth group which served as control
      received distilled water only. On the 29th day, the rats which had been fasted
      overnight were dissected under chloroform anaesthesia and blood was collected
      directly from their hearts. The blood was allowed to clot and centrifuged to
      obtain the serum which was kept in a refrigerator at -4 degrees C until used for
      analysis. Appropriate Commercial kits (Randox Laboratories, U.K.) were used to
      evaluate the serum activity or concentration of the following parameters:alanine
      and aspartate transaminases, alkaline phosphatase, cholesterol, triglycerides,
      creatinine, high density lipoproteins, total and conjugated bilirubin and total
      proteins. The fruit extract of the plant significantly elevated the serum
      concentrations of cholesterol, triglycerides, total proteins, at the three dose
      levels. The 500 and 1000 mg kg(-1) doses increased the concentrations of HDL and
      conjugated bilirubin. While only 100 and 500 mg kg(-1) doses of the extract
      reduced the level of total bilirubin. The hypercholesterolemic, hyperproteinemic,
      hypertriglyceridemic and hyper conjugated bilirubinemic effect of this extract
      coupled with the increased activity of alkaline phosphatase suggest that the
      fruit of Telfaira occidentalis may not be safe for consumption. This is quite
      contrary to the nutritional usage of the leaf and seed of this plant.

PMID- 19090137
TI  - New Bromus (Poaceae) record for the flora of Iran.
AB  - Bromus danthoniae var. uniaristata Melderis (Poaceae) is recorded for the first
      time for the flora of Iran.

PMID- 19090138
TI  - Bioaccumulation of lead nitrate in freshwater crayfish (Astacus leptodactylus)
      tissues under aquaculture conditions.
AB  - The aim of this research was to evaluate the amount of lead in the tissue of
      Astacus leptodactylus especially in their muscle which the consumed part of their
      body. In this study the crayfish was exposed to intermediate concentration of
      lead nitrate (500 microg L(-1)) for periods up to 3 weeks. In the first, second
      and third weeks bioaccumulation in various tissues was under investigation. The
      data of toxicological analysis obtained by the method of atomic absorption
      revealed that the levels of bioaccumulation of metal are different in various
      tissues of this crayfish. The accumulation of the lead in gills was the highest
      and in muscles was lowest degree. The amount of heavy metals in the tissues of
      crayfish was as follow. Gills>exoskeleton>hepatopancreas (digestive
      glands)>digestive tract>green gland>testis and ovary>muscles.

PMID- 19090139
TI  - Extruded leftover food as animal feed: I. Effect of extruded feed on growth and
      feed utilization of tilapia (Oreochromis niloticus) in Saudi Arabia.
AB  - A Laboratory experiment was used to evaluate the effect of extruded leftover food
      as an alternate source of fish diet to Nile tilapia (Oreochromis niloticus, 76.75
      +/- 1.27 g). Three experimental diets were used. Two extruded leftover food types
      [with minerals and vitamins (type-1) and without (type-2) were used to prepare
      two experimental treatments in duplicate as compared to a commercial tilapia diet
      (ARASCO) as a control. The final body weight and Specific Growth Rate (SGR) were
      not affected by different types of leftover feed. Whereas, the Feed Conversion
      Ratio (FCR) and the Protein Efficiency Ratio (PER) were significantly affected by
      the different feeds. The highest significant values of FCR was shown for fish fed
      with extruded leftover feed without premix, while Nile tilapia fed with control
      diet recorded the highest values of PER. The present study showed that the
      extruded leftover food could be used to prepare least cost diet for Nile tilapia.

PMID- 19090140
TI  - Ecological study in forest reserve of Ghasemloo (Shohada) valley and it's
      adjacent areas, Urmia-Iran.
AB  - Forest reserve of Ghasemloo valley (Shohada) and it's adjacent areas with 577
      hectare surface area has located in south of Urmia and is known as an important
      natural plant station of Urmia. It is studied with respect the important factors
      which influencing vegetation cover in whole, particularly, with refer to
      composition and Formation of plant communities. To study the area, Brown
      Blanquet's method was used. Plant samples were collected from 77 sample plots.
      The study resulted in recognition of four herbaceous types and seven shrub
      communities in study area. In addition, the investigation led to the fact that
      the most important factors which influencing the vegetation cover, are:
      geographical orientation, altitude, gradient and soil texture. More over, the
      study also resulted to preparation ofa colour vegetation map with 1/20000 scale.

PMID- 19090141
TI  - Genetic properties of milk thistle ecotypes from Iran for morphological and
      flavonolignans characters.
AB  - The aim of present study was to investigate the genetic variation within and
      between 32 milk thistle ecotypes collected from northern (23 accessions) and
      southern (9 accessions) regions of Iran along with two introduced varieties, CN
      seeds and Budakalaszi, for morphological and flavonolignans properties. The two
      collections were assessed at separate field experiments. MANOVA for all the
      morphological traits showed significant difference between ecotypes. Univariate
      ANOVA verified these differences for most of the traits in the northern ecotypes
      (first collection) while for southern ecotypes no significant differences were
      obtained for the studied traits except seed yield. Among and within ecotypes
      genotypic coefficient of variation indicated higher level of variation among
      ecotypes than within ecotypes. In both of the experiments, there was a large
      genetic variation for silybin and silymarin quality and quantity. Cluster
      analysis of 34 accessions was performed for morphological traits and silymarin
      and silybin characteristics, separately. The resulting dendrogram based on
      silybin and silymarin characteristics revealed that the native accessions such as
      Dezfoul, Fereydounkenar and Nour, had highest flavonolignans and they were better
      than the foreign varieties. Also, there was no clear relationship between
      clustering based on morphological traits and flavonolignan compounds.

PMID- 19090142
TI  - A phytosociological research on the vegetation of Ahirdagi (Afyonkarahisar).
AB  - This phytosociological study was carried out to determine the vegetation of
      Ahirdagi. The study distinguished four plant communities distributed among three
      different types of vegetation. The vegetation tables are included. Relevant types
      and associated syntaxa are as follows: Forest and shrub vegetation [Quercetea
      pubescentis (Oberd, 1948) Doing Kraft, 1955; Querco-Cedretalia libani Barbero,
      Loisel et Quezel, 1974; Carpino-Acerion Quezel, Barbero and Akman, 1978; 1-
      Ferulagini macrosciadiae-Pinetum caramanicae ass. Kargioglu; 2- Quercetum
      vulcanicae-cerridis ass. Kargioglu; 3- Stachyo tmoleae-Cistetum laurifolii ass.
      Kargioglu) and Thorn-cushion vegetation (Astragalo-Brometea Quezel, 1973;
      Onobrychido-Thymetalia leucostomi Akman, Ketenoglu, Quezel et Demirors, 1985;
      Phlomido armeniacae-Astragalion microcephali Akman et al., 1984; 4-Euphorbio
      seguierianae-Astragaletum microcephali ass. Kargioglu].

PMID- 19090143
TI  - Biology and population dynamics of the goby Pseudapocryptes elongatus in the
      coastal mud flat areas of the Mekong Delta, Vietnam.
AB  - This study describe the reproductive biological characteristics and population
      parameters of the goby, Pseudapocryptes elongatus (Cuvier, 1816), in the coastal
      mud flat areas of the Mekong Delta, Vietnam. A total of 1058 specimens was
      collected from January 2004 to June 2005 and results showed that the breeding
      season occurred with two spawning peaks in July and October. Length at first
      maturity (L(m)) was 15.4 and 16.3 cm for females and males, respectively. The
      batch fecundity estimates ranged from 2,652 to 29,406 hydrated oocytes per ovary
      in the fish ranging from 12.8 to 22.4 cm TL. Length frequency data of the goby
      ranging from 9.0 to 24.0 cm TL were analyzed using the FiSAT II software. The von
      Bertalanffy growth parameters were determined as L8 = 25.9 cm, K = 0.66 year(-1)
      and t(o) = - 0.26 year(-1). The longevity (t(max)) of the goby was estimated to
      be 4.55 years. There were two recruitment peaks with very different magnitudes
      and the means of these two peaks were separated by an interval of 5 months.
      Length at first capture (L(c)) was 10.05 cm, the instantaneous fishing mortality
      rate (F = 1.38 year(-1)) and natural mortality rate (M = 1.46 year(-1)) accounted
      for 49 and 51% of the total mortality (Z = 2.84 year(-1)), respectively. Relative
      yield-per-recruit and biomass-per-recruit analyses gave E(max) = 0.65, E0.1 =
      0.55 and E0.5 = 0.33. Results show that the fish stock is subjected to growth
      overexploitation.

PMID- 19090144
TI  - Inhibitory effect of Egyptian propolis on Fasciola gigantica eggs with reference
      to its effect on Clostridium oedematiens and correlation to chemical composition.
AB  - The chemical composition of the propolis samples was investigated by GC/MS and
      HPLC. 91 compounds have been identified, 26 compounds are being new to propolis.
      Siwa oasis propolis was characterized by the presence of diprenyl-dihydrocoumaric
      acids (4.15%), coumarate esters (10.93%), benzofuran lignans (13.47%) and valeric
      acids derivatives (11.42%). Matrooh sample was characterized by the presence of
      new ferulate esters, hydroxy acetophenones and furanon derivatives, furofuran
      lignans and sterol from pregnane type. Dakahlia propolis was a typical poplar
      propolis. The present study proved evidence of inhibitory activity of propolis on
      the vitality and hatchability of immature F. gigantica eggs, where three
      different localities in Egypt were tested for this purpose. The Siwa propolis
      showed the highest inhibitory effect than the other sources. The complete failure
      of development and death of all immature eggs were recorded at concentration of
      200 microg mL(-1) of Siwa, 400 microg mL(-1) of Matrooh and 800 microg mL(-1) of
      Dakahlia propolis. The exposed F. gigantica egg shell revealed the same features
      as the non exposed egg shell when scanning with the electron microscopy. The
      three propolis samples showed inhibition in the growth of associated bacterium
      Clostridium oedematiens (Clostridium novyi) type B to fascioliasis. The
      inhibition varied according to the propolis origin.

PMID- 19090145
TI  - Designation of an in-house ELISA for detection of VZV IgG and determination of
      antibody avidity by use of diethylamine.
AB  - Herpesviruses are ubiquitous in nature and both humans and animals harbour
      different species of this diverse family. However, only 8 species have been so
      far recovered from human beings. Different techniques (molecular and non
      molecular) have been employed for rapid and efficient diagnosis of herpesviruses
      especially in case ofimmunocompromised hosts who are considered as high risk
      individuals. An indirect in-house ELISA was standardized to measure IgG antibody
      against Varicella-Zoster Virus (VZV) in sera from different groups of
      individuals. In the process of optimization of in-house ELISA, optimal dilutions
      of antigen, serum, conjugate and monoclonal IgG antibody along with selection of
      efficient blocking buffer and washing steps of microtitre plates were studied by
      the help of checkerboarding. The results were calculated according to Specific
      Binding Ratio (SBR) and cut-off procedures. The efficiency of newly developed
      indirect in-house ELISA was attempted and results were compared with data
      previously obtained by the agency of commercial kits or other serological
      techniques. The latter helped to investigate different technical aspects of in
      house ELISA. When accuracy of ELISA was confirmed the protocol was applied in
      screening of the sera from immunocompetent and immunocompromised hosts that
      facilitated examination of the clinical aspects of the hosts. Diethylamine (DEA)
      in 20, 35 and 70 mM concentrations were used in order to assay IgG antibody
      avidity. The IgG avidity index was calculated by dividing OD of each sera
      obtained with denaturant to OD of the same specimen without application of
      denaturants. Avidity indices proved to be an important tool to differentiate
      between primary and recurrent infections and between seropositivity and
      seronegativity.

PMID- 19090146
TI  - Identification of two types of Iranian alfalfa gene pool-based on agro
      morphological traits.
AB  - There are two types of alfalfa landraces in Iran. The first is temperate
      landraces such as Hamedani, Gharah Younjeh and the second is sub-tropical
      landraces such as Bami, Nikshahri and Yazdi. Do they have different gene pools
      and could they be identified using agro-morphological traits. A total of 332
      landraces which had been collected from different parts of Iran were planted in
      the experimental field. During 1998-2002, agro-morphological traits were
      evaluated according to IPGRI descriptors. One way ANOVA analysis showed that the
      variance among accessions within provinces is not significant for mostly of
      traits, whereas it was significant among provinces. Cluster analysis revealed
      that there are five clusters which are grouped in two main clusters. The first
      main cluster consisted of landraces of central to Northern provinces. The other
      main cluster consisted of landraces of central to Southern provinces. The results
      of t-test among quantitative traits in two main clusters and distribution of
      collected accessions of each province in the produced plot based on two first
      factor of factor analysis, confirmed the cluster analysis results. Therefore
      these results revealed that those accessions which were collected from Northern
      parts of the country were genetically different from Southern accessions. As a
      result, there are two types of gene pools for alfalfa landraces in Iran. Also
      this study showed that using agro-morphological traits could be used for
      distinguishing between two types of gene pools of alfalfa landraces in Iran.

PMID- 19090148
TI  - Consequence of dam genotypes on productive and reproductive performance of dairy
      cows under the rural condition in Bangladesh.
AB  - The main objective of the present study was to evaluate the consequence of dam
      genotypes on productive and reproductive performance of different cross-bred
      dairy cows under field condition. A total of 313 dairy cow's information were
      collected from 33 Artificial Insemination (AI) Sub-centers/Points from the
      District AI center of greater Rajshahi district for a period from 1993 to 2002.
      The information of the productive and reproductive parameters were analyzed from
      questionnaires answered by 33 field assistant (artificial inseminator) and
      owner's of cow in respective of AI Sub-Center/Points as well as from reading the
      AI and 100% progeny collection Registers. In general, the mean birth weight, age
      at puberty, age at first fertile service, age at first calving, gestation length,
      post-partum heat period, days open, wastage day, service per conception, milk
      production per day, peak milk production per day, lactation length, lactation
      yield, dry period, weaning period and calving intervals were 18.8 kg, 27.9 month,
      29.2 month, 38.7 months, 278.7 days, 139 days, 160 days, 20.3 days, 1.62, 5.13 L,
      10.45 L, 282 days, 1445 L, 146 days, 10.65 months and 438 days, respectively. Dam
      genotype of dairy cows were divided into 5 groups according to their genetic
      composition. LxF, SxSL, L, LxSLxF and LxSxSL of dam genotype had significant
      effect on all the productive and reproductive performances of the dairy cows
      except on age at first calving, gestation length and weaning period. The
      genotypes of dam's of cows like LxF and LxSL showed a better performance under
      field condition at greater Rajshahi district and poor performance were recorded
      in L and LxSxSL of dam genotype. The experiment reflects that the LxF and LxSL
      genotypes of dam showed the better productive and reproductive performances of
      dairy cows under rural condition in Bangladesh.

PMID- 19090147
TI  - Optimization of composition of media for the production of extracellular
      glucoamylase by Candida guilliermendii.
AB  - The combined effects of macronutrients of media on glucoamylase production by
      Candida guilliermendii were studied using Design Of Experiment (DOE). A 2(P-k)
      factorial design was chosen to explain fifteen medium constituents: pH, Starch,
      Sucrose, Yeast extract, Peptone, NH4Cl (NH4)2HPO4, NH4NO3, CH4NO2 (NH4)2SO4,
      CaCl2, MnCl2, FeCl2, ZnCl2 and MgCl2 and analyse the results. This procedure
      limited the number of actual experiments performed while allowing for possible
      interactions between components. The p-value of the coefficient for quadratic
      effect of pH, starch and yeast extract concentration was < 0.001, suggesting that
      they were the main experimental variables having the highest effect on the
      production of glucoamylase. It was found that yeast extract had a great effect on
      glucoamylase production. The optimal combinations of media constituents for
      maximum which were chosen for further studies on production of glucoamylase were
      determined as 10 g L(-1) starch, 0.45 g L(-1) urea, 0.61 g L(-1) NH4NO3, 3 g L(
      1) Yeast extract and 0.1 g L(-1) Mg SO4.

PMID- 19090149
TI  - Association between p53 expression and Bcl-2, P-glycoprotein, topoisomerase II
      alpha, thymidylate synthase and thymidine phosphorylase as potential therapeutic
      targets in colorectal cancer patients.
AB  - We evaluated the expression of molecular markers in colorectal adenocarcinoma in
      relation to p53 protein expression. Tissue samples of 54 patients with colorectal
      adenocarcinoma were obtained at surgery at university hospitals in the years 2000
      2003. These were analyzed by immunohistochemical techniques using primary
      antibodies for p53, Bcl-2, P-gp, topoisomerase II alpha and Thymidylate Synthase
      (TS), thymidine phosphorylase/PD- ECGF (TP) and LSAB detection kit. The highest
      prevalence of expression among six analyzed markers were P-gp and p53 with 77%
      expression and the lowest one was Topo II with 35% expression. No
      clinicopathological significance was recorded in colorectal cancer patients.
      Several immunophenotypes were observed between p53 and other molecular markers.
      Additionally the prevalence of lack of expression of Bcl-2, Topo II and TS was
      higher in p53+ tumors than in p53-tumors. A significant association (p = 0.021)
      existed between p53/Bcl-2 coexpression and mean age of patients (63.5 [10.1]y vs.
      52.3 [15.2] y) and between p53/TP coexpression and sex (66.7% male; (p = 0.022).
      Overexpression of mutated p53 seen in tumor samples may alter the expression
      pattern of other molecular markers that are predictors of tumor response to
      chemotherapy regimens. Age and sex of patients could also affect the p53 related
      proteins such as Bcl-2 and TP, which can affect therapeutic outcome and disease
      prognosis. These findings emphasize the importance of tumor immunophenotypes as
      valuable prognostic or predictive markers in clinical settings.

PMID- 19090150
TI  - High frequency shoot regeneration from petal explants of Chrysanthemum morifolium
      Ramat. in vitro.
AB  - An efficient and novel method was developed to initiate multiple shoots from the
      petal which is indispensable for normal and transgenic plant of Chrysanthemum
      morifolium. The study indicates that high frequency of plant regeneration that
      would be crucial for the application of genetic transformation methods. The 7 mm
      petal explants were cultured on a Murashige and Skoog's (MS) basal nutrient
      medium containing plant growth regulators (cytokinin or auxin-cytokinin) with
      various combinations and concentrations for the study of callus formation and
      shoot induction. The highest callus formation (96%) in 4037 genotype cultured in
      MS medium supplemented with 2 mg L(-1) BA and 0.1 mg L(-1) NAA. The highest
      number of shoots was obtained from genotype 89 and 4037 in MS medium supplemented
      with 2 mg L(-1) BA and 0.1 mg L(-1) kinetin, 1 mg L(-1) kinetin and 0.1 mg L(-1)
      NAA, respectively. A significant difference in regeneration capacity was observed
      among five genotypes. Genotypes x growth regulators interaction caused
      considerable variation in the expression of regeneration responses, suggesting
      that determination of specific level of growth regulator concentration in the
      medium is necessary for a particular genotype to obtain optimum response. Strong
      seasonal variation in plantlet regeneration frequency was observed for every
      genotype. The elongated shoots were multiplied on a multiplication medium, rooted
      and acclimatized in a green house.

PMID- 19090151
TI  - Systematic study of weedy species of Setaria (L.) P. Beauv. (Poaceae) in Iran.
AB  - Weedy species of Setaria (L.) P. Beauv. (Poaceae, Panicoiodeae and Paniceae)
      compose one of the worst weed groups interfering with world agriculture and in
      other disturbed and managed habitats. These weed species (S. glauca, S. viridis
      and S. verticillata) form the foxtail species-group in Iran. In this study 30
      populations from different part of Iran were collected. Morphological traits were
      studied. Some morphological characters as texture of upper lemma, awn color and
      ligule shape are used to differentiate Setaria species group in Iran. It is
      believed that these morphological traits have a lot of overlapping. Morphological
      variations were evaluated by multivariate statistical methods. This study shows
      the systematic value of different quantitative and qualitative characters in
      weedy Setaria species native to Iran. An identification key based on studied
      characters is provided.

PMID- 19090152
TI  - Genetic polymorphism at the candidate gene in Iranian Sistani cattle (Bos
      indicus).
AB  - The genotypes for Leptin, Kappa-Casein, Calpastatin and BoLA-DRB3 loci were
      determined by polymerase chain reaction and restriction enzyme digestion method
      in native Iranian breed cattle, Sistani. Blood samples were collected from
      Sistani Breeding Station located in Zehak, Zabol in Iran. The extraction of
      genomic DNA was based on Guanidin Thiocyanate-Silica gel method. After PCR
      reaction, amplicons were digested with appropriate restriction enzymes. The
      Calpastatin locus had 3 genotypes with frequencies of 0.62, 0.29 and 0.09 for MM,
      MN and NN, respectively; kappa-Casein and Leptin had 3 genotypes with frequencies
      of 0.27, 0.57 and 0.16 for kappa-Casein, 0.77, 0.22 and 0.01 for Leptin for AA,
      AB and BB genotypes, respectively. For BoLA-DRB3 we identified 19 alleles, that
      DRB3. 2*8 had the highest allelic frequency (22.4%) and DRB3. 2*3, *29, *37 and
      *51 had the lowest allelic frequency (1%). One of the 19 alleles had a new
      pattern. Average heterozygosity values for all loci were low. Chi2-test did not
      confirm the Hardy-Weinberg equilibrium for Leptin and Calpastatin in this
      population. These data provide evidence that Iranian's Sistani breed have a good
      genetic variability, which opens interesting prospects for future selection
      programs, especially marker-assistant selection.

PMID- 19090153
TI  - Molecular detection of Streptomyces griseus isolated from Isfahan soil.
AB  - The aim of the present study was to detect Streptomyces griseus from Isfahan soil
      using biochemical, morphological and molecular techniques. Soil samples were
      collected from different regions (compost, 50 year old garden, river bed, clove,
      wheat farms and domestic yards) of Isfahan in two different seasons. One gram of
      each sample was serially diluted and cultivated in a primary isolation medium.
      Morphological shapes of colonies and vegetative hyphae were initially used to
      separate the grown bacteria of the samples. Various biochemical tests based on
      Bergey's manual of systemic bacteriology were performed to separate the
      Streptomyces from other related Genera. In order to further separate Streptomyces
      grisesus, Polymerase Chain Reaction (PCR) was used to detect the presence of aphE
      and strA genes in isolated colonies. Biochemical and morphological results,
      showed the presence of several species of Streptomyces in the collected samples.
      The expected band of 924 bp belonging to strA gene was observed in the positive
      control bacterial DNA (PTCC 1125). Several other bands were also observed in the
      positive control sample. From the total of 10 colonies that undergone molecular
      detection for the presents of strA gene, 6 colonies (W1, W3, W5, F4, F5, F26)
      showed only one band at 750 bp and four (W1, W3, F5, F26) showed an extra band of
      approximately 924 bp band as well. The expected band of 671 bp belonging to aphE
      gene was detected in positive control bacterial DNA (PTCC 1125). None of the soil
      samples, however, showed the presence of the aphE gene (data not shown).

PMID- 19090154
TI  - Assaying the presence of histone-like protein HU in Halobacillus karajensis.
AB  - Histone-Like Proteins (HLPs) in bacteria are small basic proteins that contribute
      to the control of gene expression, recombination, DNA replication and compressing
      the bacterial DNA in the nucleoid. Among the HLPs, HU protein as a dimer plays an
      important role in binding to DNA and bending it. In this study, we showed that a
      9.5-10 kDa protein with the same electrophoretic mobility as HU exists in
      Halobacillus karajensis which is a novel gram positive moderate halophile
      bacterium that was recently isolated from surface saline soil of the Karaj
      Region, Iran. The genes encoding HU protein were also assayed during this study
      by Polymerase Chain Reaction.

PMID- 19090155
TI  - Anatomical observations on nutlets of some Salvia species (Lamiaceae) from West
      Azarbaijan in Iran.
AB  - Present survey was performed on thirteen species of Salvia from West Azarbaijan
      in Iran with the aim of illustrating species interrelationships. It includes
      comparative anatomy of the species based on nutlets transverse sections. These
      sections were examined using light microscope and detailed description of nutlet
      anatomical feature for all examined taxa is provided. In this study its found
      that the nutlets showed a considerable uniformity from anatomical point of view.
      However these species can be differentiated based on thickness of pericarp layer
      and parenchymatous layers colour.

PMID- 19090156
TI  - Incorporation of plant growth regulators into the priming solution improves sugar
      beet germination, emergence and seedling growth at low-temperature.
AB  - In a series of experiments, impact of inclusion of plant growth regulators into
      the KNO3 priming solution on low temperature seed germination, emergence
      percentage and seedling growth of sugar beet was investigated. Seeds were primed
      in 3% KNO3 solution for 6 days at 25 degrees C in darkness containing one of the
      following: 0, 0.05, 0.1, 0.5, or 1 mM acetyl salicylic acid (ASA) or 1, 3, 5 or
      10 microM methyl jasmonated (MeJA). A non-primed treatment was also included in
      the experiment. Priming seeds in the presence or absence of plant growth
      regulators in general improved final germination percentage (FGP), germination
      rate (G50) and germination synchrony (G10-90) at 15 degrees C compared with non
      primed seeds which had an FGP of 42%, G50 of 11.3 days and G10-90 of 11.7 days.
      Priming seeds in KNO3 solution containing 0.05 mM of ASA resulted in the highest
      germination percentage (89%), fastest germination rate (G50 = 5.3 days) and the
      most synchronous germination (G10-90 = 10.7 days). Emergence percentages were the
      highest for the seeds primed in the presence of 0.05 mM ASA (83%) and 3 microM
      MeJA (81%) while non-primed seeds had an emergence percentage of 40%. Fastest
      emergence rate (E50) were also obtained from seeds primed in KNO3 supplemented
      with 3 microM MeJA (E50 = 14.4 days) and 0.05 mM ASA (E50 = 14.4 days). Shoot
      fresh and dry weight of seedlings were significantly affected by treatments and
      priming in the presence of 0.05 mM ASA resulted in highest seedling shoot fresh
      and dry weight. These results indicate that priming seeds in 0.05 mM of ASA or 3
      microM MeJA incorporated into the KNO3 solution can be more effective than KNO3
      alone to improve low temperature germination performance of seeds and subsequent
      seedling growth.

PMID- 19090157
TI  - Growth optimization of Zataria multiflora Boiss. tissue cultures and rosmarinic
      acid production improvement.
AB  - In order to improve the growth of Zataria multiflora tissues in vitro experiments
      in different hormonal treatments and culture media were carried out. Shoot
      cultures, established from plantlets shoot apex, were treated by different levels
      of 6-benzylaminopurine and 1-naphtalen acetic acid added to Murashige and Skoog
      medium with two conditions of active charcoal. The highest proliferation rate was
      obtained with 1 mg L(-1) 6-benzylaminopurine, without charcoal. Callus cultures
      of Zataria multiflora were established from plantlets shoot nodes on MS
      supplemented with 1 mg L(-1) kinetin and 0.5 mg L(-1) 2, 4-dichlorophenoxyacetic
      acid. Callus growth rate on three different media (MS salts and vitamins, MS
      salts with Gamborg vitamins and Gamborg salts and vitamins) was evaluated. The
      best growth was recorded on Gamborg medium (salts and vitamins) with 0.75 mg L(
      1) 6-benzylaminopurine and this medium was retained for rosmarinic acid
      production optimization experimentation. Sucrose and glucose were tested at
      different doses to compare the effect of carbohydrates on the growing rate and
      the production ofrosmarinic acid in shoot cultures and callus cultures.
      Experiments also were done at two light exposures (total obscurity or 16 h
      light/8 h dark). Very high level of rosmarinic acid was detected in callus
      tissues (158.26 mg g(-1) dry weight) as compared with propagated shoots (12.28 mg
      g(-1) dry weight). The dose of carbohydrate had a direct effect on the production
      of rosmarinic acid dependent of the type of tissues. The best ratio
      production/growth was obtained in callus cultures treated with glucose 75 g L(-1)
      under light exposure. These results indicate that, in Zataria multiflora, the
      undifferentiated state of tissues appears particularly more efficient for
      metabolic production in vitro, such as rosmarinic acid, in comparison to
      differentiated shoots.

PMID- 19090158
TI  - Spinal tuberculosis: a major public health hazard in Isfahan.
AB  - The purpose of this study is to review of spinal tuberculosis in three hospitals
      in Isfahan of Iran. We carried out a cross sectional study of 630 patients with
      tuberculosis and identified 100 patients with spinal involvement in the three
      hospitals. Tuberculosis was diagnosed based on one of a compatible clinical
      picture. A radiographic study of the spine with suspicious signs and skin tested
      were performed for each patient. Demographic data, sign, symptoms and site of
      spinal involvement were recorded. In all patients, a chest X ray and sputum smear
      and culture was performed for rouling out of pulmonary tuberculosis. Out of the
      100 patients with spinal tuberculosis, 58% were male and 42% were female. Main
      symptoms were spinal deformity, local tenderness and neurologic deficits. Fever
      and constitutional symptoms were in 80% of cases. Only 68% had a positive
      tuberculin skin test. Three percent involvement were the upper thoracic spine,
      23% the lower thoracic spine, 69% also the lower thoracic, T12 and upper lumbar
      spines, (thoracolumbar) and 5% the cervical spine. 40 cases underwent bone biopsy
      that 25% had a positive smear, whereas 62.5% had a positive culture. Histologic
      findings suggestive of tuberculosis involvement of the bone were found in 37 of
      the 40 biopsies. The most common age for spinal involvement were 20-40 years (p <
      0.05). Spinal tuberculosis may be missed in patients with no evidence of
      pulmonary. No pathognomonic imaging signs allow tuberculosis to be readily
      distinguished from other conditions. In this here, we discuss about clinical and
      histopathological findings in patients with spinal tuberculosis.

PMID- 19090159
TI  - Interpretation of fission product effects on human body.
AB  - The behaviors of fission products is studied in this study with the principal
      objective of making a comparison between Deep Atomic Binding (DAB) Approach and
      other models used to interpret the health effects of fission products on human
      body. Large numbers of fatalities, malignancies, thyroid cancer, born (genic)
      defects were predicted as health effects of fission products on human body.
      Nevertheless, the facts after real releases of fission products were not
      consistent with what was predicted. DAB Approach interprets these facts and
      reduces radiophobia as well as radiation protection expenses.

PMID- 19090160
TI  - Effects of grilling on luteolin (3',4',5,7-tetrahydroxyflavone) content in sweet
      green bell pepper (Capsicum annuum).
AB  - The content of luteloin in green bell pepper (Capsicum annuum) produced in Turkey
      were determined by RP-HPLC with DAD detection. The luteloin (3',4',5,7
      Tetrahydroxyflavone) content of green pepper samples were 46.00 +/- 0.76 mg kg(
      1) f.w. (average). The alterations of luteloin concentrations with heating
      process (grilling, kozleme) and the loss of luteloin amount were also determined.
      Luteolin contents of grilled peppers were found as 29.96 +/- 0.96 mg kg(-1) f.w.
      The method was objective and reproducible for accurate detection of luteloin in
      green pepper and other pepper varieties.

PMID- 19090161
TI  - Effects of aqueous eucalyptus extracts on seed germination, seedling growth and
      activities of peroxidase and polyphenoloxidase in three wheat cultivar seedlings
      (Triticum aestivum L.).
AB  - Evaluation of allelopathic effects of this plant on other near cultivations
      especially wheat is the aim of this study. Effects of water extracts of
      eucalyptus leaves examined on germination and growth of three wheat cultivar
      seeds and seedlings. Results showed that: germination percentage strongly
      decreased, leaf and root lengths also affected and dry and wet weights of both
      roots and shoots showed similar change patterns. Activities of peroxidase and
      polyphenoloxidase as antioxidant enzymes in roots and shoots measured. Activity
      of peroxidases increased in stress conditions and roots showed more increased
      enzyme activity than leaves. Activity of polyphenoloxidases increased only in one
      of three cultivars and again roots showed more activity of this enzyme in
      response to eucalyptus extract. Suggest that detoxification process were
      conducted mainly in roots of seedlings.

PMID- 19090162
TI  - Monthly variation of plasma concentrations of testosterone and thyroid hormones
      and reproductive characteristics in three breeds of Iranian fat-tailed rams
      throughout one year.
AB  - Nine sexually mature rams, three Shall, three Afshari and three Zandi were used
      in this study. Semen of rams was collected twice per month during the four
      seasons of the year and blood samples were obtained via jugular vein. Seminal
      characteristics, scrotal dimension and blood parameters were measured at 2 week
      intervals. Time of the year significantly (p < 0.05) affected the volume of
      semen, sperm concentration, percentage live sperm, percentage abnormal sperm,
      sperm mass motility, total sperm number, scrotal circumference, relative testis
      volume and serum levels of testosterone, triiodothyronine and thyroxine. All of
      semen characteristics, except sperm abnormality, were high in summer months than
      at other months of the year (p < 0.05). Sperm abnormality was higher in autumn
      months (p < 0.05). Relative testis volume and testicular circumference were
      higher in autumn and summer months than at other mouth of the year, respectively
      (p < 0.05). Scrotal circumference were not significant between Shall and Afshari
      breeds but comparison with Zandi breed, Scrotal circumference was bigger (p <
      0.05). The largest values for thyroid hormones synchronized with low reproductive
      performance of rams, but testosterone was highest levels at this time (p < 0.05).
      TimexBreed interaction effect was significant for sperm concentration, total
      sperm number, semen volume, testis circumference, relative testis volume, thyroid
      hormones and testosterone (p < 0.05).

PMID- 19090163
TI  - Study the effect of nitrogen fertilizer management on dry matter remobilization
      of three cultivars of rice (Oryza sativa L.).
AB  - In order to study the effect of nitrogen fertilizer management on dry matter
      remobilization among three rice cultivars, a field experiment was carried out at
      the Rice Research Institute of Iran-Deputy of Mazandaran (Amol). In 2005, a split
      split experiment in the basis of randomized complete block design with 3
      replications and 3 factors were used in which fertilizer rate (100, 150 and 200
      kg ha(-1) from urea source), fertilizer split application (3 levels in variable
      ratios in transplanting, tillering and heading stages and cultivars (Tarom,
      Shafagh and Bahar1) were the treatments. Results showed that nitrogen fertilizer
      rates and split application had significant effect on dry matter remobilization
      amount in total shoot, stem and leaves (except flag leaf) in which among
      cultivars, Shafagh had the highest amount in terms of stem and total shoot dry
      matter remobilization. This amount was obtained at the 100 kg ha(-1) nitrogen
      fertilizer and the first split application treatment. The highest rate of dry
      matter remobilization in leaves (except flag leaf) related to Bahar1 that
      obtained in 200 kg ha(-1) nitrogen fertilizer level. Also, flag leaf of Bahar1
      had the highest dry matter remobilization amount, although was not affected by
      nitrogen fertilizer rates and split application. Thus, it seams that this part
      has important role in current photosynthesis at post anthesis stage compared with
      dry matter remobilization. According to our findings, flag leaf in Tarom cultivar
      not only has no significant role in dry matter remobilization, but also act as a
      powerful sink for photosynthetic assimilates.

PMID- 19090164
TI  - The prevalence of cardiac dysrhthmias in Khozestan-Arab horses.
AB  - An observational field study was performed on a well-know purebred horses in Iran
      (Khozestan-Arab horse). The study was conducted on 105 apparently healthy horses.
      To find the prevalence of cardiac dysrhythmias in different sexes and ages, the
      horses were divided into 2 sexes (63 females and 42 males) and three age groups
      (0-4, 4-8, > 8 years old). After taking the history and performing clinical
      examination, ECG was obtained on a base apex lead system with the paper speed of
      25 mm sec(-1) and sensitivity of 10 or 5 mm mv(-1) at rest. The
      electrocardiograms were evaluated according to the criteria of normal cardiac
      rate and rhythm. Analysis variance, tuckey test, independent samples t-test and
      chi-square were used for Statistical analysis. The results showed that, 36.2% of
      the horses were affected with some types of dysrhythmias. The most frequent
      dysrhythmias were sinus tachycardia, sinus arrhythmia and heart blocks
      respectively. After exercise, many cardiac dysrhythmias were disappeared
      (physiologic dysrhythmias). Although the prevalence of cardiac dysrhythmias in
      mares and 4 to 8 years old horses were more than stallions and other age groups,
      respectively, but the differences were not significant (p > 0.05). There were
      significant differences between the heart rate of 2 sexes and one age group (less
      than 1.5 years old) with other groups (p < 0.05).

PMID- 19090165
TI  - Cryptosporidium oocysts and Balantidium coli cysts in pigs reared semi
      intensively in Zuru, Nigeria.
AB  - A cross-sectional study was conducted on the presence of Cryptosporidium oocysts
      and Balantidium coli cysts in fecal samples from semi-intensively managed pigs in
      Zuru Local Government Area of Kebbi State, Nigeria between November 2005 and
      July, 2006. A total of 632 households with human population of 5905 were
      identified in seven pig- rearing locations in the study area while 105 (16.6%) of
      these households with human population of 1105 (18.7%) reared a total number of
      3895 pigs. Physical randomization was used to select 50% representative samples
      of pig-rearing households and pigs for this study. Out of the 402 pigs from 55
      households, 207 (51.5%) pigs were positive for Balantidium coli cysts, 56 (13.9%)
      for Cryptosporidium oocysts while mixed infection was observed in 29 (7.2%).
      There is significance difference in the distribution of the two parasites in the
      pigs surveyed (p < 0.05). Young pigs were most affected with infection rates of
      33 (58.9%) Cryptosporidium oocysts, 113 (54.6%) Balantidium coli cysts and
      17(58.6%) mix infection. Human fecal samples collected from 53 individuals
      revealed 3 (5.7%) positive cases of Cryptosporidium oocysts all in young ones
      while a positive case of Balantidium coli cyst infection was found in an adult
      female. Water and soil samples from two areas were also found to contain both
      organisms. The semi-intensive system of pig rearing which allowed pigs to
      scavenge and defecate about, defective personal and environmental hygiene couple
      with the usage of untreated pig feaces as manure on vegetable farms in the study
      area can enhance the spread of these zoonotic diseases in human population.

PMID- 19090166
TI  - Assessment of wheat breeding lines for slow yellow rusting (Puccinia striiformis
      West. tritici).
AB  - A preliminary infection experiment was carried out during 2005-06 to identify
      slow yellow rusting sources of resistance in 20 NIA-wheat breeding lines along
      with Morocco as susceptible check at Nuclear Institute for Food and Agriculture,
      Peshawar. It was revealed that the current pathotypes of Puccinia striiformis
      West. tritici (Pst) were found virulent on all tested genotypes except NIA-6 and
      NIA-14. Host-pathogen compatibility in remaining lines facilitated the assessment
      of slow rusting trait and it was assessed through the epidemiological parameters
      viz., Final Rust Severity (FRS), Area Under Rust Progress Curve (AURPC) and
      Infection Rate (IR). Maximum FRS of 70% was rated in five lines while in the
      remaining 13 lines it ranged between 10 to 60%. Relative AURPC values up to 30%
      of the susceptible check were recorded for 10 lines while up to 70% for eight
      lines, showing desirable and good slow rusting behavior, respectively. Relative
      infection rate values ranged from 0 for NIA-7 to 1100-1300, recorded for eight
      lines. NIA-7 has a constant severity of 10% over assessment dates with lower
      AURPC value and was considered as better slow rusting line. Among various
      epidemiological parameters used for assessment of slow rusting trait, AURC was
      found to be a reliable parameter. Infection rate, on the other hand did not
      reveal the actual slow rusting behavior of the tested lines. Based on slow
      rusting trait, the tested lines may probably have genes for varying degrees of
      slow yellow rusting and can be used for further manipulation in wheat improvement
      program after confirmatory studies.

PMID- 19090167
TI  - A new nematode Spirocotyle otolithi n. gen, n.sp, (Camallanidae Railliet and
      Henry, 1915) from the fish Otolithus rubber (Schneider) of Karachi coast.
AB  - A new genus and species of camallanid nematode Spirocotyle otolithi is described
      here from the fish Otolithus rubber (Schneider) of Karachi coast. This is a
      medium sized nematode, pointed to its posterior extremity in male and blunt in
      female, with a buccal capsule oval in shape in both the sexes and having a sucker
      like structure in its anterior extremity. The wall of the buccal capsule is
      provided with fifteen spiral thicknings. Two unequal spicules are present in
      male. Ten pairs of caudal papillae are present, including five pairs preanal,
      four pairs postanal and one adanal. Valva in female is prominent, post equatorial

PMID- 19090168
TI  - Anti-plasminogen monoclonal antibody (MC2B8) inhibites angiogenesis.
AB  - Angiogenesis is a complex process during which of new blood vessels are produced
      from the preexisting blood vessels. Formation and growth of new vessels play an
      important role in the physiologic process (embryonic growth, tissue repair) and
      pathologic process (tumor growth, inflammation) for surviving of the tissues. In
      fact, the development of tumors is depended upon new vessel formation through
      which the tumor is provided with nutrient and oxygen. In this research, the role
      ofplasminogen conformation with MC2B8 mAb (an antibody directed against C
      terminal part of plasminogen) in clot lysis and angiogenesis is observed. In
      experimental model of angiogenesis, beads, covered with endothelial cells of bone
      marrow capillaries, are the source of endothelial cells. It coated in three
      dimensional structure to be provided through fibrin gel. Different titers of
      monoclonal antibody (30-480 microg mL(-1)) MC2B8 were added in fibrin gel. 3-5
      days after culturing of endothelial cells, growth and migration was seen as the
      result of capillary formation MC2B8 mAb delayed clot lysis and inhibited
      angiogenesis at the concentration of 240 microg mL(-1). Present findings suggest
      that these effects on capillary tube formation and clot lysis caused blockage or
      conformational changes in plasminogen epitopes involved in angiogenesis and
      fibrinolysis.

PMID- 19090169
TI  - Ex vitro survival and early growth of Alpinia purpurata plantlets inoculated with
      Azotobacter and Azospirillum .
AB  - The survival rate, shoot and root dry mass, shout number, plant growth, stem
      height and diameter, number of leaves and root length were measured in
      micropropagated plantlets of Alpinia purpurata (Red ginger) inoculated with
      Azospirillum sp. 11B and Azotobacter sp. Pachaz 008 at 10(7), 10(8) and 10(9)
      cells cm(-3) using a complete randomized experimental design. Inoculation ofA.
      purpurata plantlets with the Azospirillum sp. 11B or Azotobacter sp. PACHAZ 008
      strains induced larger stem diameter, root dry mass, number of shoots and
      increased their survival rate from 77 to 100% compared to plantlets without
      inoculation, while other plant characteristics were not affected.

PMID- 19090170
TI  - Effect of substrate quantity and shelf position on yield of oyster mushroom
      (Pleurotus sajor caju).
AB  - An experiment was conducted in Harare (Zimbabwe) in 2004 to investigate the
      effect of substrate (wheat straw) quantity and shelf position on yield of oyster
      mushroom (Pleurotus sajor-caju) using plastic tray culture. The experiment was
      laid out as a 2-way factorial in a randomized block design with five substrate
      quantities (2, 4, 6, 8 and 10 kg of wheat straw per tray) and two shelf positions
      (0.5 and 1.2 m above ground). Mushroom yield increased with an increased
      substrate quantity of up to 6 kg and thereafter remained constant. Shelf position
      had no significant effect (p > 0.05) on mushroom yield and there was no
      interaction (p > 0.05) between substrate quantity and shelf position on yield.
      Biological efficiency decreased with an increase in substrate quantity per tray.
      It was concluded that 6 kg of substrate per tray (50x35 and 20 cm deep) would
      result in optimal yields. The height above the ground at which trays are placed
      in the growing room does not affect mushroom yields.

PMID- 19090171
TI  - Effect of sugar beet root aphid, Pemphigus fuscicornis (Homoptera: Pemphigidae),
      on sugar beet yield and quality in Iran.
AB  - Pemphigus fuscicornis (Koch) is a pest of sugar beet root in warm and dry regions
      of Iran. This belongs to the Middle East and south east of Asia fauna. Nymphs
      establish colonies in root sutures and feed heavily which cause wilting and
      yellowing in beet near harvest. This study was conducted to determine infestation
      indices, damage occurrence and the necessity for control measures of this pest.
      Nymph colonies were monitored in different experimental fields that were planted
      with commonly used monogerm variety Afshari and then five infested places were
      selected. Damaged root specimens were sampled from five foci and ranked for
      infestation, yield and sugar concentration. Results indicated that there were no
      significant differences in weight, sugar concentration and impurities between
      indices 1, 2, 3 and none infested beets. Only the sugar concentration of indices
      4 showed significant differences with zero infested beets. In the other hand, no
      specimens were found with the highest population density index (indices 5).
      Therefore, the sugar beet root aphid populations did not reach to the level of
      economic damage in these experimental fields. Thus, the control measures such as
      chemical application and use of resistant varieties may be used when the colonies
      density increases to the indices four and five throughout the foci in such
      fields.

PMID- 19090172
TI  - Molecular G typing of bovine rotaviruses in Iran.
AB  - Fifty rotavirus-positive feacal samples, selected from 500 ELISA tested diarrheic
      specimens were used in this study. Viral RNA was extracted from each sample and
      reveres transcribed to cDNA. The cDNA was then amplified by oligonucleotide
      primers specific for RNA segment 9, coding for VP7. After the first
      amplification, PCR products were subjected to a multiplex semi-nested PCR to
      investigate the presence of bovine rotavirus serotypes: G6, G8 and G10. The
      results indicated prevalence of 48 and 26% for G6 and G10 serotypes,
      respectively. Twenty four percent of the samples showed a mix infection by G6 and
      G10 serotypes and no sample was found positive for the type G8. With the best of
      our knowledge this is the first report of molecular typing of bovine rotaviruses
      in Iran.

PMID- 19090173
TI  - Assessment of cervical erosion in Hamedan city, Iran.
AB  - The purpose of this study was to determine the role of socio-economic factors and
      cytology in cervical erosion. A cross-sectional study involving 410 females in
      the reproductive age group was conducted in urban health centers in Hamedan city,
      Iran. Data were collected through interviews with women, gynecological
      examination in the clinics in the health centers and laboratory tests. Cervical
      erosion was detected in 68 (16.6%) females. Out of these mild dysplasia was seen
      in (8.8%) females. High percentages of inflammatory smears (58.8%) were obtained
      in women with cervical erosion. Cervical erosion was more common in illiterate
      and women with low literacy status as compared to women with higher education.
      Majority of cases of cervical erosion were detected in women with high parity. A
      statistically significant relationship was found between lower socio-economic
      status and cervical erosion (p < 0.05). Regular cytological screening by Pap
      smear will help in early detection of carcinoma cervix.

PMID- 19090174
TI  - Pediculus capitis infestation according to sex and social factors in Hamedan
      Iran.
AB  - To determine the intensity of Pediculus capitis infestation (abundance) among
      school children, children's sex and social factors were analyzed as modifiers of
      the general prevalence of parasitism. The study included 847 school children (407
      girls, 440 boys) between 6 and 12 years, from 12 in public rural primary schools
      of Hamedan, Province of Hamedan, Iran. Classic prevalence was obtained as the
      percentage of children with nits and/or lice. The general prevalence was 6.85%
      (girls: 13.5%; boys: 0.7%, p < 0.001), head lice were much more commonly detected
      in girls than in boys. The obtained results showed that there was significant
      variations between head lice infestation and the factors such as parents'
      literacy, type of hair, previous infestation, sharing of bed and comb and care
      centers, while there was no significant variation between school grade, parents'
      job, members of family and pediculosis in the studied areas (p > 0.05). Sex and
      social factor are important modifiers of P. capitis general prevalence and degree
      of infestation. The classification of children by intensity of infestation
      allowed a more precise delimitation of this condition, which is especially
      important for disease surveillance and application of control measures.

PMID- 19090175
TI  - Effect of different sources and levels of zinc on egg quality and laying hen
      performance.
AB  - Eighty layer hens were assigned in a completely randomized design to four dietary
      treatments containing zinc sulphate or organic zinc as Albino-Zn in two levels of
      25 or 50 ppm. Feed intake was expressed on a per hen basis. Daily egg collection
      was expressed on a hen-day basis. Eggs were weighed to calculate egg mass. Feed
      conversion ratio was calculated as feed consumed per egg mass. Also all eggs
      produced on days 14, 28 and 42 were collected and used for egg quality
      parameters. Albumen height was measured and HU was calculated. The yolk and dried
      shell were weighed then albumen weight was calculated. There was no effect of
      zinc source or zinc level on egg production, egg weight or feed conversion ratio.
      However, feed intake was lower in the group receiving 50 mg kg(-1) organic zinc.
      There were no significant treatment differences for weight of egg components or
      shell thickness, but albumen height and HU were higher in the second fortnight
      for the groups receiving organic zinc at 25 or 50 mg kg(-1) than in the un
      supplemented group.

PMID- 19090176
TI  - Comparative histomorphological study of uterus between laying hen and duck.
AB  - The present investigation was carried out on oviductal duck and laying hen to
      comparing of histomorphological structures of them. For this purpose, a total of
      forty adult healthy ducks and hens (each of them twenty), aged 1-1.5 years, were
      used. After dissecting them, some morphological parameters such as: total weight
      and length of oviduct were measured and then in each of specimen some
      morphological parameters such as; length, width and thickness of uterus were
      measured. For histological studies, after tissue preparation and staining with H
      and E, histological layers of uterus were recognized and the size of them with
      micrometry method were determined. By using t-test and analyzing factors between
      duck and hen we concluded that total weight and length of oviduct in hen was
      greater than duck and the difference was significant (p < 0.05). By comparing of
      dimensions and weight of uterus between duck and hen revealed that, in hen the
      mean of uteral weight (14.98 +/- 2.58 g) and uteral width (5.00 +/- 0.91 cm) were
      greater than duck. It was observed in duck (9.27 +/- 2.04 g) and (3.19 +/- 0.58
      cm), respectively. In histometrical studies, the length of tunica mucosa, primary
      fold and muscularis mucosa width in duck were greater than hen. There was a
      significant difference in length of secondary fold and in hen (164.47 +/- 34.16
      microm) was greater than duck (119.80 +/- 27.89 microm).

PMID- 19090177
TI  - Studies on antimicrobial activity of Perionyx excavatus.
AB  - The antimicrobial activity of vermiextract was assessed against four human
      pathogenic microorganisms. Especially strains of Proteus species are a prominent
      cause of urinary tract infection in children. The present investigation deals
      with particular urinary tract pathogenic organisms like E. coli, Proteus,
      Providencia, Morganella species. Screening was performed by disc diffusion
      method. The zone of inhibition range from 17 to 19 mm against 1.0x10(8) cells of
      each culture at 1 mg concentration of vermiextract. Vermiextract was most
      effective against Proteus species. The MIC (Minimum Inhibitory Concentration) was
      estimated by microdilution method.

PMID- 19090178
TI  - Essential oil compositions of Cymbopogon parkeri STAPF from Iran.
AB  - Aerial parts of aromatic grass, Cymbopogon parkeri STAPF, were collected at
      flowering stage from Kerman province of Iran. The essential oil of air dried
      samples obtained by hydro-distillation method. The compositions of the essential
      oil were determined by the use of GC and GC-MS. Nineteen (98.7%) constituents
      were identified. The main constituents were piperitone (80.8%), germacrene-D
      (5.1%), santolinyl acetate (2.1%) and alpha-eudesmol (2.1%).

PMID- 19090179
TI  - On the track of mesothelial progenitor cells from the peritoneal cavity
      transplanted to immunodeficient mice.
AB  - Mesothelial progenitor cells have been reported to reside in either the monolayer
      of mesothelium, submesothelium or within the peritoneal cavity as free floating
      cells. As a putative plasticity has been reported for the mesothelial progenitor
      cells and considering the potential implications of the establishment of a novel
      resource of stem/progenitor cells in gene and cell therapeutics and tissue
      engineering, we conducted an in vivo tracking of transplanted mesothelial cells.
      In order to induce immunodeficiency, the recipient mice were treated with 32 mg
      kg(-1) of daily Cyclosporine. On days 14, 30 and 60 post transplantation, brain,
      heart, skeletal muscle and lung tissues were screened by a modified FISH method
      directed to the Y chromosome of donor cells. Fluorescence harboring cells were
      analyzed by flow cytometry and fluorescent microscopy. The data confirmed by PCR,
      demonstrated the existence morphology alteration of the donor cells in various
      organs of the recipient mice, notably in the skeletal muscle and lung and less in
      the heart and brain. Immunostaining of recovered cells from the nervous recipient
      tissues suggests differentiation of mesothelial cells in the new
      microenvironment.

PMID- 19090180
TI  - The impact of atmosphere circular system on coupling features of spring net
      primary productivity with precipitation in East Asia.
AB  - In many East Asia regions, spring (from March to May) precipitation is an
      important restricting factor to vegetation growth. By analyzing the coupling
      features of spring NPP with precipitation, the result was found that the response
      features of NPP to precipitation were mainly embodied within the leading six NPP
      precipitation paired-modes. The explanation rates of the leading six paired-modes
      to the covariance of NPP-precipitation were 42.91, 23.29, 9.96, 5.60, 5.04 and
      3.95%, respectively and total to 90.75%. The temporal correlation coefficients of
      the leading six paired-modes were 0.830, 0.889, 0.841, 0.747, 0.912 and 0.923,
      respectively and all the correlations were significant at the level of 0.001. In
      some high altitude regions, there was no obviously corresponding relationship
      between NPP and precipitation in the leading two paired-modes and the reason of
      it may be that spring temperature was the main restricting factor to NPP. In
      middle and low altitude regions, the effect of precipitation on NPP was
      relatively more notable. Nine atmospheric circulation factors in spring affected
      the patterns of NPP and precipitation greatly and the affected regions with
      explanation rate to precipitation and NPP changes over 50% shared 65.58 and
      60.41% to the whole study area, respectively.

PMID- 19090182
TI  - Immune response to measles vaccine in primary school students.
AB  - This cross sectional study was performed to estimate the prevalence of
      serological evidence of immunity to Measles in primary school students (age 6-12)
      that have a history of twice vaccination against measles, on 9 and 15 month old
      and determining the appropriate age to re-vaccination. Multistage sampling was
      used to select students to participate in the present study. Immunization status
      and documentary evidence of immunization was recorded from the Personal Health
      Record. Measles antibodies were measured using enzyme-linked immunosorbent assay
      (ELISA). Sufficient blood for antibody testing was obtained from 1665 children,
      975 (57%) were girls and 720 (43%) were boys, respectively and mean age was 9.17
      +/- 1.53 years. On the whole, 1198 subjects (72%) were seropositive and 467 (28%)
      were seronegative at all. Among girls and boys, 72 and 71%, were seropositive
      respectively. These differences were not statistically significant between the
      two sexes (p = 0.404). Antimeasles antibody titer decreased with increasing age
      from 6 to 10 years old, (76.5% in 6 years old group vs. 71% in 10 years old
      group) and then rise to 78% in 11-12 years old group. These differences were not
      statistically significant between age groups (p = 0.775). the immunity produced
      by the measles vaccine is not enough. Decrease of protective effect of measles
      vaccine, suggests the necessary of preschool revaccination.

PMID- 19090181
TI  - Protective effect of Nigella sativa seeds against lead-induced hepatorenal damage
      in male rats.
AB  - Heavy metals are widely distributed in the environment and some of them occur in
      food, water, air and tissues even in the absence of occupational exposure. Among
      of these lead, (Pb) is a hazardous substance to human and animals. The present
      study was carried out to investigate the possible protective effect of co
      administered Nigella sativa seeds on lead acetate-induced rats' toxicity in
      particularly on liver and kidney. Thirty-six male rats were divided into six
      groups, 6 rats each. The first group was served as a control, while the second
      group was fed on the basal diet with Nigella sativa addition, whereas the other
      groups contained lead acetate (10 and 20% of LD50) with and without Nigella
      sativa supplementation for six weeks. At the end of the feeding period, rats were
      fasted over night and anesthetized and blood and tissue samples were taken for
      biochemical and histopathological studies. The results of this study revealed
      that lead acetate caused significant elevations in AST, urea, creatinine, total
      cholesterol and triglycerides in serum. Lead treatment also produced significant
      decrease in serum total protein and albumin. Histopathological observations
      showed severe damage in the liver and kidneys. Its damaged areas were measured
      using Image analyzer. Combined treatment of lead-exposed animals with Nigella
      sativa showed marked improvement in both biochemical and histopathological
      findings as well as reduction in the damaged areas. These experimental results
      strongly indicate the protective effect of Nigella sativa against toxic effect of
      lead on liver and kidney tissues.

PMID- 19090183
TI  - Salt tolerance of wheat according to soil and drainage water salinity.
AB  - To determine salt tolerance of spring wheat genotype (On_Farm 9) to soil salinity
      (ECe) and drainage water salinity (ECd), a pot experiment containing three
      irrigation water salinities of 4, 9 and 12 dS m(-1) and four leaching levels of
      3, 20, 29 and 37% was conducted in a completely randomized design arranged as
      factorial with 7 replications on a silty clay loam soil during 2005. The results
      showed that decrease of leaching water quality and quantity significantly
      increased soil and drainage water salinity and decreased crop yield and
      evapotranspiration. Application of leaching water fraction in the range of 20-29%
      were highly significant in decreasing soil salinity, drainage water salinity and
      increasing grain yield, while the most increase in crop evapotranspiration
      occurred in the range of 29-37%. This study shows that the effects of increase of
      soil salinity on grain relative yield are more significant than effects of
      increase of salinity of drainage water and wheat has greater threshold value in
      drainage water salinity than soil salinity method. The correlation of relative
      grain yield (Ry) with ECe and ECd indicated that ECd could estimate Ry as well as
      ECe.

PMID- 19090184
TI  - Prevalence of human herpes virus-8 and hepatitis B virus among HIV seropositive
      pregnant women enrolled in the Mother-to-Child HIV Transmission Prevention
      Program at Saint Camille Medical Centre in Burkina Faso.
AB  - The aims of this research are: i) to evaluate the prevalence of HHV-8, HBV and
      HIV among pregnant women, ii) to determine the percentage of these co-infections
      and iii) to estimate the frequency of the mother-to-child transmission of HIV
      among HBV and HHV-8 positive mothers. Thus, 379 pregnant women attending ante
      natal consultation in Saint Camille Medical Centre were subject to HIV, HHV-8
      antibodies and the viral marker Hepatitis B Surface Antigen (HBsAg) detection. We
      observed 48/379 (12.66%) HIV seropositive subjects. Among them, HIV-1 type
      infection was predominant (95.83%), only 2/48 (4.17%) subjects had a dual HIV-1
      type and HIV-2 type infection, no single HIV-2 type infection was detected.
      38/379 (10.02%) subjects were infected by HHV-8 and 30/379 (7.91%) were HBsAg
      positive. HHV-8 and HIV Co-infections rates were high within HBV positive
      patients and we had respectively 20.00 and 16.67%. 10.42% HIV positive women were
      coinfected by HBV while 12.50% were infected by HHV-8. Then, 15.79% subjects HHV
      8 positive were co-infected by HBV or HIV. In spite of the PMTCT protocol
      application, five (10.42%) HIV positive women transmitted the virus to their
      children. Two HIV positive mothers were co-infected by HHV-8 and one by HBV.
      Among the 5 HIV infected, one mother (20.0%) was HBV positive and two (40.0%) HHV
      8 positive. Although we did not have a large sample which would show large
      prelalences of the infections, we could put forward that the Co-infection of the
      HIV with one of these viruses (HBV or HHV-8) could favorite the mother-to-child
      transmission.

PMID- 19090185
TI  - Morpho-physical variation of fruits and impact on almond production of djansang
      (Ricinodendron heudelotii Baill.) in west and centre of Cameroon.
AB  - The aim of this study were to describe different forms of fruits and the
      establishment of correlation between the different morpho-physical parameters in
      view of evaluating their incidence on production of almonds in Ricinodendron
      heudolotii in three localities (Balamba, Mbalmayo, Santchou) in Cameroon.
      Tropical forest trees belonging to the Euphorbiaceae family, R. heudelotii is
      used by the local population in traditional medicine and as lipidic source.
      Fruits randomly harvested in these three localities have revealed six types
      namely: one new type constitute of four seeded fruit with four lobes and five
      previous type constitute of single seeded fruit with one lobe; single seeded
      fruit with one aborted lobe; two seeded fruit with two lobes; two seeded fruit
      with unequally developed lobes; three seeded fruit with three lobes. This
      variability is expressed by differences at the level of morphological parameters
      (mass of fruit and seed) and physical parameters (thickness of shell, ratio of
      longitudinal diameter and cross diameter section of seeds, capacity to liberate
      almonds). Analyses of variance, correlation and principal component have showed
      that, seeds extracted from fruits of Mbalmayo have shell thicker whereby those of
      Santchou liberate much shell. In the same way, accession of Mbalmayo has a total
      mass for 1500 fruits estimated 1.5 times superior to those of Balamba and 1.19
      time superior to those of Santchou. In fact, study of morpho-physical parameter
      shows that to choose the fruits having a high capacity to liberate almond,
      ellipsoid-oblate form of the seeds and thickness of shell are good indicators and
      for this effect, accession of Santchou is recommended. Accessions of Balamba and
      Santchou having less rate of seed abortion are more productive.

PMID- 19090186
TI  - The influence of continuous rice cultivation and different waterlogging periods
      on morphology, clay mineralogy, Eh, pH and K in paddy soils.
AB  - The effect of different rice cultivation periods on the properties of selected
      soils in alluvial plain were studied in Mazandaran province (north of Iran) in
      2004. Soils were sampled form 0, 6, 16, 26 and over 40 years rice cultivation
      fields. In each treatment three soil profiles and six nearby auger holes were
      studied. The present study results indicated that continuous rice cultivation
      have changed soil moisture regime from xeric to aquic, soil color from brown to
      grayish, surface horizons from mollic to ochric epipedon and soil structure
      changed from granular or blocky to massive. Therefore, the soil order has changed
      from Mollisols to Inceptisols. No illuviation and eluviation of clay minerals
      occurred as a consequence of rice cultivation. X-ray diffraction analysis showed
      that clay minerals in non-rice cultivated field were illite, vermiculite,
      montmorillonite, kaolinite and chlorite, but in rice field were illite,
      montmorillonite, kaolinite and chlorite, respectively. In contrast of
      montmorillonite, the amount of illite and vermiculite have been decreased by
      increasing periods of rice cultivation. The pH values of the saturated soil
      surface in six weeks past plantation have shifted toward neutrality. While Eh
      value of non-paddy soils were about +90 mv, surface horizons of paddy soils at
      field conditions had Eh value about +40, -12, -84, -122 mv, respectively. The
      amounts of organic matter and available Fe, Mn, Zn and Cu were increased whereas
      available K was decreased in paddy soils.

PMID- 19090187
TI  - Effect of plant growth regulators on in vitro biological control of Fusarium
      oxysporum by Trichoderma harzianum (T8).
AB  - In this study the effect of two plant growth regulators (indolacetic acid, IAA
      and gibberellic acid, GA3) and also Trichoderma harzianum (T8) on the
      phytopathogen fungus Fusarium oxysporium (F15) was investigated. IAA and GA3 with
      15 and 30 ppm concentration have no significant effect on T. harzianum (T8)
      growth. The biocontrol activity of T. harzianum on F. oxysporum was slightly
      decreased by the presence of IAA and/or GA3. Addition of 40 ppm of GA3 to the
      culture medium of F. oxsporum increased polygalacturonase activity about 100%. A
      strong increasing effect on chitinase activity (60%) by T. harzianum (T8) was
      observed in the presence of phytopathogenic fungus F. oxysporum, but 40 ppm IAA
      and/or GA3 decreased about 47% of chitinase activity of T. harzianum.

PMID- 19090188
TI  - Effect of elicitors and a biogenetic precursor on paclitaxel production in cell
      suspension cultures of Taxus cuspidata var. nana.
AB  - To stimulate the production of taxol (paclitaxel) by cell suspension cultures of
      Taxus cuspidata var. nana, two kinds of elicitors and a biogenetic precursor were
      used in F4G4 culture medium. Paclitaxel production was enhanced by each elicitor
      as well as by the biogenetic precursor and by a combination of the two elicitors
      or one elicitor and the biogenetic precursor. The amount ofpaclitaxel produced
      (16.6 mg L(-1)) was greatest when the cell suspension cultures were conducted in
      F4G4 medium containing chito-heptaose (8 mg L(-1)) and jasmonic acid (21 mg L(
      1)). The productivity was enhanced 4.1 fold compared to the control. The amount
      of paclitaxel produced was increased by supplying air to the cultures, though the
      productivity depended on the amount of air supplied. However, no enhancement of
      production was observed when a combination of air and chito-heptaose was provided
      to the cell suspension cultures.

PMID- 19090189
TI  - Effects of in vivo and in vitro zinc and cadmium treatment on sperm
      steroidogenesis of the African catfish Clarias gairepinus.
AB  - The aim of present research to study the effects of in vitro and in vivo exposure
      of catfish to heavy metals to determine whether the steroidogenic activity in
      sperm would be affected by two heavy metals contaminants, zinc and cadmium. Three
      groups of six male African catfish were fed from the sexually immature juvenile
      stage, with diet containing 1000 ppm zinc, cadmium or zinc + cadmium for 110 days
      and 20alphaHSD activity in milt of these fish were compared with six other
      control fish fed with normal diet. The 20alphaHSD enzyme activity was also
      measured in in vitro incubation of milt from six control fish with different
      concentrations (0, 0.1, 1,3, 10, 30, 100, 1000 and 3000 ppm) of zinc, cadmium or
      zinc + cadmium. A very high 20alphahydroxy steroid dehydrogenase enzyme activity
      was found in all sperm incubations of African catfish. This enzyme converts 17
      hydroxy progesterone (17P) substrate to 17,20alpha-dihydroxy progesterone (17,
      20alphaP) product and the rate of enzyme activity is related to substrate (17P)
      concentrations. Significant differences (p < 0.05) in enzyme activity in
      converting 17P to 17,20alphaP were found between in vitro incubations of sperm
      with different concentrations of zinc, cadmium or zinc + cadmium and control
      group (0 ppm). Significant differences (p < 0.05) in enzyme activity and
      17,20alphaP production were found between fish fed with diet containing 1000 ppm
      zinc or cadmium and the group fed with diet containing 1000 ppm zinc + cadmium
      and control groups. The results showed that 20alphaHSD enzyme activities in fish
      sperm may be used as indicator of water contamination with heavy metals and their
      bioaccumulations in testis of aquatic animals.

PMID- 19090190
TI  - Genetic variation of jointed goatgrass (Aegilops cylindrica Host.) from Iran
      using RAPD-PCR and SDS-PAGE of seed proteins.
AB  - Genetic variation of 28 populations of jointed goatgrass (Aegilops cylindrica
      Host.), collected from different parts of Iran, were evaluated using both RAPD
      PCR and SDS-PAGE of seed proteins. The diversity within and between populations
      for the three-band High Molecular Weight (HMW) subunits of glutenin pattern were
      extremely low. Out of 15 screened primers of RAPD, 14 primers generated 133
      reproducible fragments which among them 92 fragments were polymorphic (69%).
      Genetic similarity calculated from the RAPD data ranged from 0.64 to 0.98. A
      dendrogram was prepared on the basis of a similarity matrix using the UPGMA
      algorithm and separated the 28 populations into two groups. Confusion can happen
      between populations with the same origin as well as between populations of very
      diverse geographical origins. Our results show that compare to seed storage
      protein, RAPD is suitable for genetic diversity assessment in Ae. cylindrica
      populations.

PMID- 19090191
TI  - Kid's growth and dairy performances of pure breeds and crossed caprine genotypes
      in the coastal oases of southern Tunisia.
AB  - A data issued from 16 years performances schedule of local goat, Alpine,
      Damascus, Murciana and crossed groups was used to study the genotypes productive
      behaviour under Tunisian oases conditions. The aim is to evaluate the
      possibilities of local goat productivity improvement by cross breeding in
      intensive mode and also, to choose the better improving breed and the propice
      crossing level. So, data of periodic individual weighing was used to estimates
      kid's weight at some standard ages and dairy performances such as, daily milk
      average, total production by lactation and milking period of studied genetic
      goats groups. Statistical analysis of about 1928 kid's weights and 1923
      individual goat milking shows that, the cross breeding allows to improve the
      growth performances since the first generation with respect to local population
      production. ANOVA test shows an important effect of genotypes and environment
      upon kid's weights (p < 0.01). The kid's weight average at birth and at 120 days
      age was about 3.49 and 15.78 kg, respectively. The cross breeding second
      generation allows the better improvement of local goat potentialities kid's
      weight at 120 days reaches 16.19 kg for Damascus x local genotype. The dairy
      production with this generation is, about 248 kg for the Alpine one, of 181 kg
      for Damascus and 190 kg for Murciana, is only 137 kg by lactation for the local
      breed.

PMID- 19090192
TI  - Investigation of seed vigor and germination of canola cultivars under less
      irrigation in padding stage and after it.
AB  - The laboratory experiment was a factorial based on a Completely Randomized Design
      with four replications during 2005. Factors included two irrigation levels
      (normal irrigation (irrigation after 60 mm evaporation from class a pan) and less
      irrigation in padding stage and after it) and six winter cultivars (Licord,
      Okapi, Orient, SLMO64, Zarfam and Opera). The seeds used in this experiment
      produced under less irrigation (moderate drought stress) and they were three
      months in storage. The seed vigor was tested in laboratory experiment by three
      vigor tests, including Standard Germination test, cold test, Accelerated Ageing
      Test. Result showed that the accelerated aging test had significant differences
      on all of character in this study. Mean Comparing, showed canola cultivars had
      significant effect on Root/ Shoot ratio, abnormal seedling, hard seed, seedling
      fresh weight, MTG and FGP. Less irrigation levels had significant effect on total
      and shoot length, ratio root/shoot length and MTG.

PMID- 19090193
TI  - Are natural killer cells distributed in relationship to nerve fibers in the
      pregnant mouse uterus?
AB  - Specialized lymphocytes, called uterine Natural Killer (uNK) cells, appear in
      human and rodent uteri and become abundant at implantation sites during
      decidualization and early pregnancy. The hallmark of human uNK cells is intense
      expression of CD56, a neural cell adhesion glycoprotein (NCAM-1) while mature
      (granulated) mouse uNK cells express asialoGM1, a brain ganglioside. Murine uNK
      cells initiate the normal structural changes induced in maternal spiral arteries
      by pregnancy but regulation of their recruitment, localization and activation is
      incompletely understood. To address whether uNK cell distribution is co-localized
      with nerve fiber distribution, sections of gestation day (gd) 6-12 implantation
      sites from C57BL/6 (B6) mice were studied. Nerve fibers reactive with antibodies
      to pan neurofilament 150 kD or with tyrosine hydroxylase, an enzyme restricted to
      sympathetic fibers, were present the walls of branches from the uterine artery in
      the mesentery. Reactivity was lost as the vessels crossed the myometrium and
      entered endometrium/decidua. Periodic Acid Schiffs reactive uNK cells were absent
      from the mesentery and enriched in decidua basalis where they transcribed NCAM-1
      and associated with non-innervated segments of the uterine arteries, including
      spiral arteries. These data suggest that the localization and activation of
      mature uNK cells are unlikely to be neurotransmitter regulated.

PMID- 19090194
TI  - Electrophoretic analysis of total protein profiles of some Lathyrus L. (Sect.
      Cicercula) grown in Turkey.
AB  - In this study, total 8 species (Section Cicercula) belong to 14 different
      geographic distributions collected from Turkey have been studied for the analysis
      of seed storage protein profiles to examine their relationship by Sodium Dodecyl
      Sulphate Polyacrilamide Gel Electrophoresis (SDS-PAGE) technique. Hierarchical
      cluster analysis and Euclidean distance were used for comparison between species
      and calculating the genetic resemblance respectively. Dendogram was formed using
      average linkage. Electrophoretic protein profiles of seed cotyledons were showed
      that all species formed two clusters. The first one consisted of the L.
      stenophyllus, L. hirsutus, L. chloranthus, L. cicera and L. sativus second one by
      three species (L. annuus, L. cassius and L. phaselitanus). In addition, very
      little differences were observed in total protein profiles of the examined sample
      species (L. cicera, L. hirsutus and L. chloranthus) from nine geographical
      regions belong to section Cicercula. Protein amount was found to be highest in L.
      hirsutus and lowest in L. cicera.

PMID- 19090195
TI  - Influence of phenological stages and method of distillation on Iranian cultivated
      Bay leaves volatile oil.
AB  - Leaves of Bay (Laurus nobilis L.) were collected in different phonological stages
      and air-dried. Volatile oil of the leaves were obtained using hydro- and steam
      distillation and the chemical composition were analyzed by GC and GC/Mass and
      identified in comparison with authentic compounds. The yield of essential oil
      were 0.8 to 1.5 v/w% and the major compounds were; 1,8 Cineol, alpha-terpinyl
      acetate and Sabinene. Because of the interesting yield of the oil and presence of
      1,8-Cineol as the major compounds, the bearing ripe fruit stage in the mid of
      September is the best time for harvesting the Bay leaves in Iran.

PMID- 19090196
TI  - Determination of organophosphorus insecticides (malathion and diazinon) residue
      in the drinking water.
AB  - In this study, the amount and origin of the pollution of Karaj river and Amir
      Kabir dam, which is the most important supply of Tehrans (capital of Iran)
      drinking water with malathion and diazinon, have been assessed by High
      Performance Thin Layer Chromatography (HPTLC) technique. This is a descriptive
      and cross-sectional study. After initial assessments, four stations were selected
      for water sampling. In all stations, sampling was done in one day, one week, two
      weeks, one month, two months and three months after insecticide spraying.
      Extraction and separating of organophosphorus insecticides from water samples was
      done by acetone and methylen chloride solvents, using decanter. Then, the residue
      of malathion and diazinon insecticides was determined using HPTLC technique. The
      residue of malathion and diazinon in water decreases with increasing the distance
      and time of spraying. The residues of malathion and diazinon insecticides at
      station 1 and 2, which were close to spraying places, 1-2 months after spraying
      was more than allowed limits. But at the ending stations (3 and 4), malathion and
      diazinon were detectable just in the 1 day and 1 month after spraying,
      respectively. It is unlikely that Tehran's drinking water be polluted with these
      two insecticides and the most adverse effect can be seen in the area of spraying.
      Therefore not only the environment, but also the people in area of Karaj river
      are at risk of chronic toxicity with malathion and diazinon through consuming
      polluted water and agriculture products.

PMID- 19090197
TI  - The treatment of wastewater containing crude oil with aerated submerged fixed
      film reactor.
AB  - An aerated submerged fixed-film (ASFF) bioreactor was developed to treat an
      artificial wastewater based on crude oil. Bee-Cell 2000 was used as support media
      having porosity of 87% and a specific surface area of 650 m2 m(-3). The system
      was able to achieve 70.87-93.12% removal efficiencies of Chemical Oxygen Demand
      (COD) in the organic loading rate range of 1.310 to 15.797 g COD m(-2) day(-1).
      Data gained exhibited that the effluent COD concentration ranged between 68.68
      and 292.60 mg L(-1) at organic loadings experienced. Therefore, an ASFF process
      showed that it was feasible to treat high oily wastewater in order to meet the
      discharge standards.

PMID- 19090198
TI  - Study of sugar beet cyst nematode life cycle using plant tissue culture method.
AB  - After optimization of sterilizing of cyst and larva second stage of Heterodera
      schachtii, possibility of using nematode on seedlings of sugar beet (Beta
      vulgaris L.) in in vitro conditions were studied using sterilized larvae of beet
      cyst nematode. For this purpose, non sterile cysts were extracted from infected
      soil and hatched into zinc chloride solution with concentration of 0.5 g L(-1).
      Then, for preparation of sterile second stage larvae, several sterilizing
      treatments were used. Mean comparisons were performed between sterilized live
      larvae number by Duncan's method. Results showed that 70% ethanol for 1 min
      followed by 2.5% hypochlorite sodium for 5 minutes and 0.1% hypochlorite sodium
      for 20 min were best treatments for disinfecting cysts and larvae, respectively.
      In parallel, two nematode susceptible sugar beet varieties were applied to
      produce seedlings in in vitro culture. PG(oB) medium containing different
      hormonal compositions was used for producing of hairy roots and inoculation of
      seedling with sterilized larvae. After nematode inoculation tests, daily
      observations were done by counting cysts and stained roots and larvae under
      stereomicroscope. Between 5-12 cysts formed on the roots of each seedling from
      two varieties 40 days after inoculation. As a result, it seems that this
      technique can be used for sugar beet germplasm evaluation to screen nematode
      resistant genotypes in in vitro controlled condition.

PMID- 19090199
TI  - Investigation of diarrhea agents less than 5 years of age in summer in
      Gaziantep/Turkey.
AB  - Pathogens causing summer diarrhea examined to detect among children less than 5
      years of age in Gaziantep. We conducted among 100 children with diarrhea during
      summer at the pediatric hospital of Gaziantep. In stool samples from children,
      Rotavirus with Rotatect kit (Dade Behring, Germany), Entamoeba spp. with direct
      microscopy and bacterial pathogens with cultural techniques investigated. Cystic
      form of Entamoeba spp. was determined in 61 (61%) and Rotavirus antigen in 25
      positive samples (25%). A predominant bacterium was determined in total 87 stool
      samples (87%). Despite of only cystic form of Entamoeba spp. was determined in
      seven, only bacteria in 22 and only Rotavirus in one; two of them were determined
      in 67 out of stool samples. According to comparison with stool samples belong to
      various months we have found that, Rotavirus and E. coli are the most pathogenic
      agents in August more than June and July.

PMID- 19090200
TI  - Abscission of pistachio flowers and fruits as affected by different pollinators.
AB  - This study was conducted in Ceylanpinar State Farm to determine influence of
      pollens of 9 different pollinators on the flower and fruit abscission of the
      pistachio. Comparison of pollinator effect on the abscission of flowers and
      fruits of 3 pistachio cultivars showed that pollens of Pistacia vera L. may
      increase or reduce flower and fruit abscission. Flower and fruit abscission
      occurred primarily during the flowering and small-fruit period, that the June and
      pre-harvest abscissions were low. Data collected for 3 consecutive years revealed
      that 83.4 to 88.2% of the flowers and fruits of Kirmizi pistachio cultivar
      abscised mainly during an initial 50 days after Full Blooming (FB). Siirt
      cultivar abscised during an initial 35 days after FB with a rate of 82.1 to
      90.9%. Abscission rate of Ohadi cultivar were 84.5 to 88.6% that occurred during
      an initial 50 days after FB period. Males noted as 12 and 13 resulted the highest
      abscission in Siirt cultivar. Results demonstrated that pollinators affect flower
      and fruit abscission in pistachio.

PMID- 19090201
TI  - Physiological responses of broiler chicks fed various level of dopamine and zinc.
AB  - The influences of dopamine (DA) and zinc (Zn) on some physiological parameters of
      plasma such as growth hormone, cholesterol, 3-glyceride and growth rate, feed
      conversion ratio and abdominal fat of broilers between the ages of 21 to 42 day
      were investigated. The experiment was designed on a total of 180 commercial meat
      type chicks as a randomized complete block with a 3x2x2 factorial arrangement of
      treatments with three levels of DA (0, 50 and 100 mg kg(-1)) and two levels of Zn
      (0 and 40 mg kg(-1)) in each sex. At the first day of trial, chicks were randomly
      distributed in 36 boxes at the same condition until day 15. Then, the treatments
      were administered in a low dosage for acclimating of chicks to them. From day of
      21, the main dose of treatments was used. The effects of DA and Zn and
      interaction between them on cholesterol concentration of plasma were significant
      (p < 0.05). But the effects on concentration of growth hormone (GH) and 3
      glyceride of plasma were not significant. The maximum concentration ofcholesterol
      in plasma was observed in male chicks administered 40 mg kg(-1) of Zn and the
      minimum concentration was related to female chicks administered 50 mg kg(-1) of
      DA. In this period, the main and interaction effects of all treatments on weight
      gain mean of chicks were significant. Also, Zn and DA and interaction of DA x sex
      improved feed conversion ratio (p < 0.05). The results of this experiment
      confirmed the lipolytic effect of DA on plasma cholesterol and abdominal fat and
      also showed that consumption of 100 mg kg(-1) of DA plus 40 mg kg(-1) of Zn cause
      to improve growth performance of male chicks.

PMID- 19090202
TI  - Effects of acetylsalicylic acid on germination, growth and chlorophyll amounts of
      cucumber (Cucumis sativus L.) seeds.
AB  - Germination activities, various growth parameters (primary root length, hypocotyl
      length, primary leaf length, plant length and increase in fresh weight) and
      chlorophyll (a+b) amounts of cucumber seeds exposed to 0, 10(-5), 10(-4), 10(-3)
      and 0.5x 10(-2) M aqueous solutions of acetylsalicylic acid (ASA) for 48 h were
      established. While 0.5x 10(-2) M ASA significantly prevented germination activity
      of the seeds, other concentrations did not produce any effect, either positive or
      negative. Meanwhile, 0.5x 10(-2) M ASA inhibited radicle growth of the germinated
      seeds, while 10(-5) M ASA increased radicle growth. Other concentrations of ASA
      did not affect radicle growth. The following findings were obtained from the one
      week seedlings exposed to ASA for 48 h: 0.5x10(-2) M ASA prevented growth
      (lengthening) of root, hypocotyl, leaf and plant and increased chlorophyll (a+b)
      amount with an increase in fresh weight. Contrary to 0.5x 10(-2) M ASA
      application, these features of the seedlings (except for the leaf length) were
      encouraged by 10(-5) M ASA. 10(-3)) M ASA only prevented root growth and reduced
      chlorophyll (a+b) amount. Other concentrations of ASA did not bring about any
      positive or negative effect on the features studied.

PMID- 19090203
TI  - Response of rice advance line PB-95 to potassium application in saline-sodic
      soil.
AB  - A field experiment was conducted to evaluate the response of rice crop to
      potassium fertilization in saline-sodic soil during 2005. Soil samples were
      collected before transplanting of rice crop and analysed for physical and
      chemical properties of the soil. In this experiment five rates of K2O (0, 25, 50,
      75 and 100 kg ha(-1)) were applied in the presence of basal doses of N and P2O5
      i.e., 110 and 90 kg ha(-1), respectively. Whole of P, K and 1/2 of N were applied
      at the time of rice transplanting. Twelve and halfkg ha(-1) ZnSO4 was also
      applied 15 days after rice transplanting. The remaining half of N was applied 30
      days after rice transplanting. The system of layout was Randomized Complete Block
      Design with four replications. The net plot size was 6x4 m. Fertilizer sources of
      NPK were urea, TSP and SOP, respectively. Rice salt tolerant line PB-95 was used
      as test crops. The data of growth parameters and yield was recorded and samples
      of paddy and straw were collected treatment-wise and analysed for N, P and K
      contents. Soil samples after harvesting the crop were also collected, processed
      and analysed for the changes in the extractable soil K. The results showed that
      increasing rates of potassium fertilizer increased the number of tillers m(-2),
      plant height (cm), 1000-paddy weight and paddy as well as straw yield
      significantly. Maximum paddy (3.24 t ha(-1)) and straw (3.92 t ha(-1)) yields
      were obtained in T5 (100 kg K2O ha(-1)) which was at par with T4 (75 kg K2O ha(
      1)). With increasing rates of potassium fertilizer, concentration of potassium in
      paddy and straw increased significantly. After harvesting the crop, the
      extractable potassium contents of soil increased from that of the original soil.
      It was concluded from the results that there was an increase of 30.65% in paddy
      over control by applying potassium (100 kg K2O ha(-1)) in saline-sodic soil.

PMID- 19090204
TI  - Hepatic triacylglycerols and plasma non-esterified fatty acids and albumin levels
      in cross breed cows in Ahvaz city of Khuzestan Province of Iran: an abattoir
      study.
AB  - The aim of the present study was to compare the hepatic triacylglycerols (TAG)
      and total lipid and plasma Non-Esterified Fatty Acids (NEFA) and albumin in cows
      in different stages of productivity slaughtered at Ahvaz abattoir. So, a total of
      203 blood and liver samples were collected from the indigenous hybrid cows
      immediately after being slaughtered at the abattoir. The cows were divided into 4
      groups according to their pregnancy statuses: 1-8 months pregnant, 8-9 months
      pregnant, less and more than 1 month of parturition. Percentage of TAG and Total
      Lipids (TL) were measured in the liver and NEFA and albumin were measured in the
      blood circulation. All the liver samples in this study showed some degrees of
      fatty infiltration. The accumulation of fat in the liver rose significantly (p <
      0.001) during the first month after parturition and returned to the same level of
      pregnancy after one month. We also noticed that plasma NEFA concentration was
      significantly higher (p < 0.05) during the first month of parturition and serum
      albumin level relegated to its lowest level (p < 0.05) in the last month of
      pregnancy. These results reveal that fatty liver is quite common in all the
      animals in the region especially in their early lactation. These findings
      indicate the necessity of reconsideration in the animal's food policies in the
      area and some especial approaches during the early phase of lactation.

PMID- 19090205
TI  - Ovicidal activity of acrolein vapors to Indian meal moth eggs of various ages.
AB  - The effect of acrolein vapors against carefully aged eggs of Indian meal moth at
      27 +/- 1 and 17 +/- 1 degrees C at different dosage levels of acrolein over
      various exposure times was determined. Considerable variation in the
      susceptibility of different age groups of eggs was apparent in the fiducial
      limits of the LD50 values. At both temperatures and 24 h exposure period, eggs
      aged 1-2 day-old were more tolerant to acrolein than other age groups. In all
      bioassays, eggs exposed to higher dosages of acrolein developed at smaller rate.
      This was significant for the eggs, which were exposed to the highest dosage for
      24 h. Increasing the temperature from 17 +/- 1 to 27 +/- 1 degrees C greatly
      increased the efficacy of acrolein. Overall, at 27 +/- 1 degrees C eggs of P.
      interpunctella were killed by less than one-fourth of the dosage required for
      control at 17 +/- 1 degrees C. Acrolein achieved 50% mortality with a dosage of
      3.80 mg L(-1) in 1-2 day-old eggs at 27 +/- 1 degrees C. At this temperature
      hatching was retarded and greatly reduced when eggs aged 1-2 day-old were exposed
      to 32 mg L(-1) of acrolein for the 24 h exposure period. There was no evidence of
      a hatch delay longer than the time spent under vapors for eggs exposed at 17 +/-
      1 or 27 +/- 1 degrees C, indicating that some development must have occurred
      under fumigation.

PMID- 19090206
TI  - Susceptibility status of different life stages of Tribolium castaneum Herbst
      (Col: Tenebrionidae) to spinosad.
AB  - Red flour beetle, Tribolium castaneum, is one the most important and worldwide
      pest of stored-products. To evaluate the susceptibility of different life stages
      of this pest we used a commercial formulation of biorational insecticide,
      Spinosad, Tracer against adults, young and old larvae and pupae using topical
      application bioassay method. Mortality was recorded after exclusion of pupae and
      24, 48 and 72 h posttreatment for the other life stages. Spinosad did not cause
      pupal mortality. Comparison of LD50 values of different life stages of T.
      castaneum at 48 h exposure-time revealed that, young larvae and adults were more
      susceptible to spinosad than the old larvae. Overlapping of 95% CL revealed
      similarity of susceptibility of young larvae and adult insects to spinosad. Due
      to compatibility of spinosad with environment, this compound could be considered
      as a useful tool in the control of the pest in question.

PMID- 19090207
TI  - Genetic relationships among six Iranian goat populations based on random
      amplified polymorphic DNA markers.
AB  - The objectives of this study were to assess the genetic variability among six
      Iranian goat breeds including: Markhoz (MR), Korki of South Khorasan (KK), Black
      Lori (BL), Najdi (NJ), Korki of Raeini (KR), Tali (TL) and to evaluate the
      genetic relationships between populations using RAPD markers. The genetic
      characterization of these genetic resources is essential to conservation and
      breeding programs. Blood sample (50 individuals per breeds) were collected from
      spreading location of these breeds. DNA extraction was carried out by Salting-Out
      method. Initially, a total of 16 ten and eleven-nucleotide arbitrary primers were
      used but 10 of 16 primers revealed a pattern with scorable amplified bands. From
      a total number of 115 scored bands 62 (53.9%) and 53 (46.1%) were described as
      polymorphic and monomorphic, respectively. The average number of bands per primer
      11/5 and with sizes varying from 220 to 2310 bp in length. Nei's genetic
      distances varied between 0.081 and 0.227 in the populations. The phylogenetic
      tree was reconstructed on Neighbor-Joining method and showed two main separated
      groups. One includes KK, TL, KR in a branch and then NJ. Another consists BL and
      MR. This research was showed that RAPD technique is an useful tool for evaluation
      of genetic variation among of domesticated animals.

PMID- 19090208
TI  - Effects of supplemental dietary biotin on performance of Holstein dairy cows.
AB  - An experiment was conducted to evaluate the effect of different levels of biotin
      on productive performance of Holstein dairy cow. In this experiment a change-over
      design with twelve multiparous cows, three rations and three periods was
      employed. Ingredients of the basal diet were alfalfa hay (24%) corn silage (16%)
      and concentrate (60%) on dry matter basis. The experimental diets 1 to 3
      contained 0, 10 and 20 mg of biotin per day, respectively. The rations were fed
      to cows as Total Mixed Rations (TMR), but biotin was top-dressed on the a.m.
      allotment of ration. The cows were individually ad libitum and milked three times
      per day. Daily milk yielded was recorded and samples of the milk were taken once
      per week for determination of milk composition. Blood were taken in end of each
      period. Dry Matter Intake (DMI) and milk yield of cows were not affected by
      biotin. Also milk compositions were not affected by biotin. The average of Fat
      Corrected Milk (FCM) yield for 4% fat for rations contain 0, 10 and 20 mg day(-1)
      biotin, respectively 25.45, 26.2 and 25.9 kg day(-1) were calculated. Blood
      concentration of were unaffected by different levels of biotin. The differences
      between averages of the milk cows were not significant.

PMID- 19090209
TI  - Protective effects of selenium and zinc on changes in catecholamine levels of
      brain regions in lead intoxified rat.
AB  - Lead is a common environmental toxic element for almost all biological systems.
      The nervous system is the primary target for the lead exposure. In the past few
      years, increasing considerations have been given to investigate the interaction
      occurring between toxic metals and some essential metals including Se and Zn with
      Pb. It has been shown that some trace elements could reverse the toxicity of lead
      on tissue functions. In this study the protective effects of Zn and Se on lead
      toxicity were investigated. Results of short time study showed that,
      intrapritoneal administration of Pb (13.5 mg kg(-1)) daily for 2 weeks reduced
      the catecholamine levels of cortex by 25, mid-Brain by 21 and cerebellum by
      25.6%, respectively. Administration of the same amount of lead in combination
      with either Zn (0.5 mg kg(-1)) or Se (0.4 mg kg(-1)) reduced catecholamine levels
      of cortex by 8.3 and 18.3, mid-brain by 6, 10.9 and cerebellum 23, 6%
      respectively. Daily administration of lead alone (4 mg kg(-1)) for 60 days
      reduced catecholamine level of cortex by 27.4 and mid-Brain by 47.8 and
      cerebellum by 39%, respectively. When the same amount of lead in combination with
      Zinc (0.5 mg kg(-1)) and/or Se (0.4 mg kg(-1)) was administration daily for 60
      days, results showed that catecholamine level of cortex was reduced by 9, 20 and
      mid-brain by 22.6, 29 and cerebellum 25, 16%, respectively. It is concluded that
      lead reduced catecholamine levels in different brain regions and Zn or Se might
      be able to reverse this reduction and protect brain function to some extent from
      lead toxicity.

PMID- 19090210
TI  - The effect of ginger extract on blood urea nitrogen and creatinine in mice.
AB  - The present study is going to determine whether ginger has positive or negative
      effects of kidney. A hydro alcoholic extract of ginger was administered
      intraperitoneally (IP) every 48 h to male mice for a period of 20 days. Control
      group received saline containing equal volume of ethanol. Blood Urea Nitrogen
      (BUN) and creatinine were measured spectrophotometrically. Administration of
      ginger extract markedly decreased the BUN concentrations in experimental mice in
      a non linear fashion with regard to the administrated dosages. However, little
      changes were observed in the levels of creatinine in these animals as compared
      with control group. It is concluded that ginger may have a beneficial effect for
      removal of urea from plasma and it may be considered as a therapeutic herb to
      manage renal function in patient with uremia.

PMID- 19090211
TI  - Study of genetic diversity in some olive (Olea europaea L.) cultivars by using
      RAPD markers.
AB  - RAPD markers variations were studied in eleven olive cultivars. Seventeen RAPD
      primers out of 27 produced 610 bands in total. Four hundred forty four bands were
      polymorphic bands (72.70 %) and 166 bands were monomorphic (27.20 %). Primer C05
      produced the highest number of bands (56), while primer C03 produced the lowest
      number of bands (7). Specific bands were observed in some of the cultivars, which
      may be used in the cultivars discrimination. Different similarity coefficients
      determined among the cultivars studied, showed the highest value of similarity
      between cultivars Kroneiki and Manzanila. Different clustering methods showed
      distinctness of the olive cultivars studied. The grouping of the cultivars did
      not correlate completely with their place of origin or fruit characteristics.

PMID- 19090212
TI  - Effects of age and temperature on calling behavior of carob moth, Ectomyelois
      ceratoniae, zell. (Lepidoptera: Pyralidae) under laboratory conditions.
AB  - The sexual calling behaviour of Ectomyelois ceratoniae, (zell.) was observed in
      the laboratory under 16L: 8D photoperiodic regime and three different constant
      temperatures, 20, 25 and 30 degrees C. E. ceratoniae, females showed a broad late
      scotophase peak of calling activity without any calling throughout the
      photophase. Most females started calling during the eclosion day on, regardless
      of the temperature. With increasing age, moths initiated calling significantly
      earlier at night and the mean time spent calling increased significantly on
      successive days of calling. There was an inverse relationship between mean time
      spent calling and mean onset time of calling (r = -0.8079, p < 0.0001) and these
      parameters significantly affected by age and square of temperature.

PMID- 19090213
TI  - The effect of animal manures on susceptibility of cowpea Var. moussa local to
      infection by root-knot nematode; Meloidogyne javanica Treub.
AB  - The effect of three different types of animal manures namely; poultry, goat and
      cow dung on the susceptibility of cowpea (Vigna unguiculata (L.) Walp) Var moussa
      local to root-knot nematode infection caused by Meloidogyne javanica was tested
      in a replicated pot experiment. Manured plants were inoculated with 2000 eggs of
      M. javanica while uninoculated manured plants served as control for each manure
      type and unmanured but inoculated plants as general control. The result showed
      that unmanured and inoculated plants were susceptible to M. javanica to varying
      degrees. Plants applied with poultry manure were more resistant to root-knot
      nematode infection followed by those applied with cow dung and goat dropping in
      that order. The most susceptible plants were those inoculated but not applied
      with manure. Gall index and resistance rating showed that plants fertilized with
      poultry manure, cow dung and goat droppings were resistant, moderately resistant
      and susceptible, respectively.

PMID- 19090215
TI  - The histological examination of Mus musculus' stomach which was exposed to hunger
      and thirst stress: a study with light microscope.
AB  - In this study, the histological changes observed in Mus musculus' stomach mucosa
      which was exposed to hunger and thirst were examined. Pieces from chest and
      stomach cavities were taken in the 1st, 2nd, 3rd, 4th and 5th days following last
      feeding. These tissue specimens were fixed by using 10% neutral formalin which
      was compressed. After routine tissue checks, the tissue pieces were sunk into
      paraffin and some blocs were prepared. With the aim to examine histological
      structures of the pieces taken, they were colored with Hematoxylin and Eosin (H
      and E). An increase in the number of blood cells taken part in stomach tissue was
      observed in the first twenty four hours. A widening in glandular epithelium lumen
      was seen after two days. A tendency to slim was observed in mucosa layer of the
      surface and glandular lumen during hunger. In the stomach mucosa, structural
      changes were caused by hunger and thirst. It was found that these changes were in
      direct proportion with hunger and thirst duration.

PMID- 19090214
TI  - Antimicrobial resistance among Escherichia coli strains isolated from healthy and
      septicemic chickens.
AB  - There is a clear association between heavy antimicrobial consumption in poultry
      industry and the recovery of resistant bacteria. This was a case-control study of
      396 E. coli strains isolated from clinically affected broiler chickens and 132
      strains from healthy controls to compare the antimicrobial resistance rates.
      Antimicrobial resistance testing of 525 avian E. coli strains isolated in Kashan
      Iran showed very high levels of resistance to 11 antimicrobials tested,
      especially to trimethoprim-sulfamethoxazole (98.7%) and to ciprofloxacin (69.7%).
      The prevalence rate of resistant E. coli to ciprofloxacin and erythromycin in the
      samples isolated from chickens with colibacillosis was significantly higher than
      healthy controls. In addition, to prevent the emergence of cross-resistance with
      human enteric pathogens, controlled use of these antimicrobial agents in
      veterinary practice is recommended.

PMID- 19090216
TI  - Productivity potentials and nutritional values of semi-arid zone earthworm
      (Hyperiodrilus euryaulos; Clausen, 1967) cultured in organic wastes as fish meal
      supplement.
AB  - In the present study 60 Adult Earthworms (H. euryaulos) of weight and length
      range 1.7-3.0 g (mean-2.34 +/- 0.91 g) and 13.0-28.0 cm (mean-21.5 +/- 5.8 cm),
      respectively were cultured for 12 weeks. The productivity potential and nutrient
      composition of earthworm (H. euryaulos) cultured in two rearing substrata
      (Cellulose Substrate (Control)--Coded Hs1 and Dry Neem and leaves and soil
      Substrate--Coded Hs2) were assessed using six wooden boxes stocked in triplicates
      at the rate of 92.7 g earthworms per box. The higher total final weight, weekly
      weight gain, relative growth rate, specific growth rate and survival of 400.6 g
      kg(-1) of substrate, 25.7 g/week/substrate, 332.5, 0.76/day and 99.0% while the
      lower of 367.5 g kg(-1) of substrate, 22.9 g/week, 296.4, 0.71/day and 98.0% were
      recorded in earthworm cultured in cellulose substrate and the soil substrate
      respectively. The proximate analyses, mineral compositions and amino acids
      indices were comparable to those of conventional fish meal. Based on the results
      of this study, the utilization of cellulose substrate is recommended for the
      culture of earthworm and the inclusion of the earthworm meal is guarantee as a
      reliable and nutritional dependable fish meal supplement.

PMID- 19090217
TI  - Lichen flora of Pamukkale (Hierapolis), Turkey.
AB  - A list of 82 lichen taxa is reported from Pamukkale (Hierapolis) in the province
      of Denizli. Sixty four taxa from the study area are new records for the province.
      Four taxa are new to Turkey: Lecania sylvestris, Lecanora sambuci, Opegrapha
      herbarum, Peltula patellata.

PMID- 19090218
TI  - The effects of salt and storage temperature on microbiological changes in hot
      smoked mirror carp (Cyprinus carpio L.).
AB  - In this study, microbiological changes during processing and preservation of
      smoked mirror carp (Cyprinus carpio L.) fillets were examined. In the processing
      phase the brining in two different salt concentration and smoke were used. The
      conservation is realized in two different ambient temperatures. Starting from raw
      material, a(w) and pH levels as well as mesophilic, psychrophilic, staphylococcus
      micrococcus, coliform, the yeast and mould counts were determined at every stage.
      In conclusion, the period preservation of smoked mirror carp fillets was
      dependent on salt concentration and preservation temperature.

PMID- 19090219
TI  - The Pleurotus eryngii species-complex in Kurdistan region of Iran.
AB  - Pleurotus eryngii species-complex are known to be well distributed in Kurdistan
      region of Iran. During a survey in 2003-2005 fourteen wild populations of the
      Pleurotus eryngii species-complex were collected from Sanandaj, Hane Gelan and
      Saral areas. Echomorphological studies and pairing tests showed that all isolates
      were belong to P. eryngii and located into two groups associated with three
      Umbelliferous host plants including isolates associated with Prangos and
      Pimpinella with smaller spores and Ferula haussknechtii with larger spores. In
      this study we introduce Ferula haussknechtii as a new host species of P. eryngii
      in the world.

PMID- 19090220
TI  - Xanthan production by a native strain of X. campestris and evaluation of
      application in EOR.
AB  - In this study, we used a native strain of X. campestris for xanthan production in
      lab-scale fermentor and the product was recovered with organic solvents and
      dried. Then we studied the potential usage of our products in different harsh
      conditions, including heat, pH and salinity treatments. Furthermore, we used 2D
      micromodel for microbial oil recovery investigations. According to present
      experiments, temperature and salt contents did not have a significant influence
      on rheological behavior of xanthan solutions and these aqueous solutions
      maintained at least 80% of their primary viscosity. In addition, these solutions
      were resistant to a broad range of pH variations. Viscosity of the xanthan
      solution was increased as it was heated over 120 degrees C. Micro-model
      experiments showed that the most efficient concentration of xanthan for Enhanced
      Oil Recovery (EOR) is 1000 mg L(-1) and 53% of original oil in place was
      recovered, which showed remarkable increase comparing to original oil in place
      that was recovered (31%) from sole water flooding. The same or even better
      results were obtained from native xanthan, when its properties were compared to
      those of a commercial sample which was gifted by NIOC.

PMID- 19090221
TI  - Antimicrobial susceptibility of environmental bovine mastitis pathogens in west
      central Iran.
AB  - The purpose of this study was to describe antimicrobial susceptibility of
      environmental mastitis pathogens isolated from dairy herds of Chahar Mahal
      province in west central Iran. Out of the 620 milk samples collected from the
      four districts, 180 were CMT (California mastitis test) positive that cultured
      and yield, 7 (3.88%) coagulase negative Staphylococci (CNS), 15 (8.33%)
      Streptococci other than agalactiae and 17 (9.44%) E. coli. CNS resistance to
      penicillin was 14.28% but for streptomycin, Oxytetracycline and Colistin, were
      28.57%. Non agalactiae Streptococci resistance to Oxytetracycline and Kanamycin
      were 20 and 13.33%, respectively. E. coli resistance to penicillin,
      oxytetracycline, streptomycin, erythromycin and Colistin were 88.23, 82.35,
      76.47, 76.47 and 52.94%, respectively.

PMID- 19090222
TI  - Intracellular localization of glutamine synthetase in a nitrogen-fixing
      cyanobacterium Anabaena cylindrical.
AB  - The major route of ammonia assimilation is the reaction which is catalyzed by
      glutamine synthetase to give ammonia. Cell-free extracts and purified thylakoid
      membranes using differential centrifugation and density gradient techniques were
      assayed for the percentage activity of the enzyme. Glutamine synthetase was
      detected in all cell-free extracts. Seventy six percent of the enzyme activity
      was found associated with the thylakoid membranes. Using antiserum raised to the
      thylakoids, 78.5% inhibition of the enzyme activity was obtained.

PMID- 19090223
TI  - Isolation of clinical strains of Pseudomonas aeruginosa harboring different
      plasmids.
AB  - Aim of this study was to investigate the presence of plasmids among the strains
      of P. aeruginosa isolated from clinically diagnosed cases in Tehran in 2006. A
      total of 38 strains of P. aeruginosa were isolated. With the exception of one
      isolate, all P. aeruginosa strains harbored at least one plasmid band. The
      electrophoretic analysis of plasmid DNAs showed different number of plasmid bands
      among the strains tested. The DNA band of 1.4 kbp was evident in 84.2% of the
      strains. Approximately 71 and 21% of the isolates harbored concomitantly two and
      three plasmids, respectively. Isolation of strains with diverse types of plasmids
      suggests the different cluster of P. aeruginosa might be disseminated during the
      current study period.

PMID- 19090224
TI  - Potential for improving crop yields through better water management in rainfed
      regions.
AB  - This study was conducted to determine the effect of water supply at critical
      growth stage of sorghum in Arid Zone Research Institute, D.I. Khan. The results
      indicated that the yield components and grain yield were significantly affected
      by water supply. Irrigation applied at heading stage of the crop significantly
      increased plant height, maturity period, fresh and dry weight of heads plot(-1),
      1000 grain weight and grain yield of sorghum irrespective to cultivars. Maximum
      grain yield of 3319 kg ha(-1) was obtained with irrigation as against 2206 kg ha(
      1) obtained from un-irrigated treatments. The plant height, fresh and dry weight
      of heads plot(-1), 1000 grain weight and grain yield of different cultivars were
      also different significantly irrespective to irrigation. Maximum grain yield of
      2976 kg ha(-1) was produced by the cultivar DS-2000 compared to 2550 kg ha(-1) by
      DS-97 Yarik. The interaction between irrigation and cultivar as regards yield and
      yield components of sorghum was non significant. The findings of this study
      suggested that the grain yield of sorghum can be increased by 50% with irrigation
      applied at the heading of sorghum.

PMID- 19090225
TI  - Frequency of different types of ovarian cancer in Vali-e-Asr Hospital (Tehran
      University of Medical Sciences) 2001-2003.
AB  - Purpose of this study was to report histology specific age adjusted ovarian
      cancer incidence rates from 2001-2003 in Tehran University Hospital (valie-Asr
      hospital). This was a case series study including all microscopically confirmed
      cases of ovarian malignancies from 2001-2003. There were 152 cases of ovarian
      cancer, 102 (67.1%) epithelial type, 26 (17.1%) germ cell tumors, 14 (9.2%) sex
      cord stromal and 10 (6.6%) metastatic ovarian tumors. Present results were
      compatible with results from nonwestern countries. Epithelial type tumors and sex
      cord-stromal tumors were more prevalent after the age 50 (40 and 44.4%
      consequently). Germ cell tumors were more prevalent before 20(16 cases, 61.5%)
      (chi2 = 42.54, p-value = 0.000). Stage of disease in epithelial type tumors was
      advanced in most of patients but most germ cell tumors and sexcord-stromal tumors
      were stage I (chi2 = 19.6, p-value = 0.000). Present study showed that epithelial
      ovarian tumors in comparison to western countries are less frequent in Iran but
      still this histologic type is the most prevalent type of ovarian malignancy in
      this area of the world. Of course in younger patients we can predict more
      probability of germ cell tumors with more localized disease and better prognosis.

PMID- 19090226
TI  - Effect of varying dietary protein sources on growth and spawning performance and
      gonad maturation of red tilapia reard in sea water.
AB  - Four-week-old Red tilapia fry with an average weight of 1.9 g were reared in
      saline water (36%) for 190 days on 6 formulated iscaloric diet of protein level
      (28%). The experiment was conducted in glass aquaria. Six diets were formulated
      including a control diet based on fish meal (diet 1) and fish silage (diet 2) and
      soybean (diet 3). The other 3 based diets supplemented with 35% fish meal and 60%
      fish silage (diet 4), 35% fish meal +65% soybean diet (5) and 50% fish silage
      +50% soybean (diet 6). There were six treatments in duplicates. The results
      indicate that supplementation with 65% fish silage let to a significant (p<0.05)
      growth performance (final weight gain 152.2 +/- 1.1 g, SGR 1.08 and daily gain
      0.80 +/- 0.06 g day(-1)) and efficient feed utilization (FCR 1.9, PER 2)
      comparable to other diets. Complete replacement with soybean resulted a
      significant (p>0.05) low growth performance (weight gain 2.43 +/- 0.06 g, SGR
      0.65 and 0.41 +/- 0.01 g daily weight gain) and less efficient in feed
      utilization (FCR 2.9 and PER 1.2). The present study also investigated the
      reproductive performance of red tilapia in sea water. The six diets were fed to
      red tilapia fries. The first spawning of the brood stock of fish groups occurred
      at almost the same age. There was a significant (p<0.05) difference in the
      absolute fecundity fertilization and hatching rate of fertilized eggs among fish
      fed soybean and the other diets. While no significant difference in the spawning
      intervals, gonad maturation, egg size, were resulted.

PMID- 19090227
TI  - Evaluation of different empirical models of crop/weed competition to estimate
      yield and LAI losses from common lambsquarters (Chenopodium album L.) in maize
      (Zea mays L.).
AB  - Usefulness and validity of different empirical yield loss models at describing
      the effect of common lambsquarters competition in maize were evaluated in a two
      year experiment in Karaj during 2001 and 2002 growing seasons. Experimental
      factors were density (1st year: 2, 5, 10 and 15 plants m(-2); 2nd year: 6.6, 13.3
      and 20 plants m(-2)) and the relative emergence time (1st year: simultaneous to,
      at 2-3 and 4-5 leaf stages of maize; 2nd year: simultaneous to, at 2-3 and 5-6
      leaf stages of maize) of common lambsquarters. Results indicated that the highest
      maize yield and LAI losses were observed at simultaneous emergence of weed and
      maize resulted in 85 and 92% yield loss and 73 and 53% LAI loss in the first and
      second years of experiments, respectively. Also, delaying common lambsquarters
      emergence reduced its competitive ability against maize. Comparison of different
      empirical models revealed that the empirical yield loss models based on density
      and the relative time of weed emergence and the weed relative leaf area, also the
      rectangular hyperbolic yield loss model based on weed density were more reliable
      at predicting maize yield and LAI losses according to their high coefficient of
      determination (R2). Also, results indicated that the negative effect of the
      relative time of common lambsquarters emergence on maize yield loss was more than
      weed density, so that the rectangular hyperbolic yield loss model based on weed
      density was more capable at predicting yield loss at each of weed emergence time.

PMID- 19090228
TI  - Sensitivity of two wheat species's seeds (Triticum durum, variety Karim and
      Triticum aestivum, variety Salambo) to heat constraint during germination.
AB  - The aim of this study is determine the effect of different temperature regimes on
      germination of wheat seeds and early germination events. Germination is very
      sensitive to environment conditions, particularly the temperature. Physiological
      and biochemical responses of wheat seed germination during time at various
      temperatures (5, 15, 25, 35 and 45 degrees C) have shown that optimal temperature
      (25 degrees C) favorites a good aptitude to germinate, whereas low (5 degrees C)
      and high temperature (45 degrees C) were extend the delay of germination.
      Residuary dry matter's mass of germinating, both Karim and Salambo wheat species,
      Seeds at 5 and 45 degrees C decreased lightly. This show a less mobilization of
      reserves to embryo. The activity of totals solubles peroxidases changes with
      temperature of wheat seed germination. At low (5 degrees C) and high (45 degrees
      C) temperatures, for both two cultivars, peroxidase activity decreases during
      germination. With exception, during imbibition (2 h), only 45 degrees C involves
      a high stimulation of this activity for Karim cultivar. This increase is
      considered as a biochemical response to high temperature. In control temperature
      (25 degrees C), we have obtained a light increase in peroxidase activity in
      comparison with that of dry seeds for both these two wheat species. At the end of
      this study, we have studied the effect of heat stress on totals proteins content.
      Nevertheless, both for these two wheat cultivars, at 5 degrees C there is no a
      markedly change in proteins amount during germination. In control condition (25
      degrees C) of germination, there is a slight decrease in this content.
      Germination under high temperature, for Karim variety, induces a rapid synthesis
      of Heat Shock Proteins (HSPs) and concomitantly a weak degradation of normal
      proteins. The opposite phenomenon was observed for Salambo variety (weak
      synthesis of HSPs and important degradation of normal proteins).

PMID- 19090229
TI  - Use of mycobacterial interspersed repetitive unit-variable-number tandem repeat
      typing to study Mycobacterium tuberculosis isolates from East Azarbaijan province
      of Iran.
AB  - The aim of present study was to determine the genotypes of isolates from East
      Azarbaijan province by this method. We performed (MIRU-VNTR) analysis of strains,
      isolated from 127 patients during a period of September 2002 to March 2003 in
      tuberculosis centers of the province. Among 127 isolates, we found 93 distinct
      MIRU-VNTR patterns, including in 21 clustered patterns and 72 unique patterns
      from isolated strains. The discriminatory power of MIRU-VNTR typing in present
      study was high (HGDI = 0.9932) for isolates. In clusters similar patterns of
      Nakhichevanees patients and Iranian patients was revealed in three clusters which
      showed Nakhichevanees patients referred to tuberculosis centers of province could
      be a source for transmission of tuberculosis. Tuberculosis in this province is
      relatively in good condition. The allelic diversity of our samples was lower than
      previous studies. These results indicate that MIRU-VNTR can be a useful and first
      line tool for studying genetic diversity of M. tuberculosis isolates in regional
      setting such as East Azarbaijan province of Iran.

PMID- 19090230
TI  - Foliar nutrient dynamics and foliar resorption in Quercus brantii lindley along
      an elevational gradient.
AB  - Foliar mass per area (mg dm(-2)) -based nitrogen and phosphorus concentrations,
      specific leaf mass (mg dm(-2)) and absolute and proportional resorption in
      Quercus brantii was investigated along a topographic gradient from 450 to 850 m
      altitude. Foliar N and P concentrations in Q. brantii exhibited significant
      differences with respect to topographic position and sampling dates in all of the
      studied parameters. A sharp decrease was observed from April to September in
      terms of Specific Leaf Mass (SLM) values. However, mass per area-based absolute
      and proportional N resorption was lowest at 450 m, while absolute and
      proportional P resorption was lowest at 850 m. Significant correlations were
      found between mass per area-based leaf nutrient concentration and foliar
      resorption except for the correlations between absolute P resorption and foliar P
      concentrations at 450, 650 and 750 m during full-leaf expansion and 850 m during
      senescence, respectively.

PMID- 19090231
TI  - Determination of the anastomosis grouping and virulence of Rhizoctonia spp.
      associated with potato tubers grown in Lincoln, New Zealand.
AB  - A total of 58 isolates of Rhizoctonia spp. (46 R. solani and 12 binucleate
      Rhizoctonia) were recovered from potato tubers showing black scurf disease
      symptom during the 2004 growing season in Lincoln, New Zealand. The isolates were
      assigned to 5 Anastomosis Groups (AG) ofR. solani AG-3 (54.34%), AG-5 (28.26%),
      AG-8 (8.69%), AG-4 (6.52%) and AG-2-2 IIIB (2.17%) and six anastomosis groups
      ofbinucleate Rhizoctonia, AG-K (25%), AG-Bi (25%), AG-Ba (8.33%), AG-C (8.33%),
      AG-D (8.33%) and AG-E (8.33%). Two isolates of BNR did not anastomose with any of
      the tester strains and remain unidentified. In pathogenicity tests that were
      carried out on radish, carrot, lettuce, onion, tomato and hemp, it was found that
      all the isolates of both R. solani and binucleate Rhizoctonia to be virulent at
      varying degrees to these 6 plants species from different families. In these
      tests, isolates of AG-3 and AG-8 from R. solani population caused the highest and
      lowest disease severity on all 6 plant species, respectively. In population of
      binucleate Rhizoctonia, on the other hand, the highest and lowest disease
      severities were caused by the isolates of AG-D and AG-Ba on all test plants,
      respectively. When the results of the pathogenicity tests were examined in terms
      of the susceptibility levels of the plants, the most resistant plant was tomato
      against different AGs of R. solani and BNR. On the other hand, radish was the
      most susceptible plant species tested in this study against both R. solani and
      BNR isolates.

PMID- 19090232
TI  - Effects of timing and defoliation intensity on growth, yield and gas exchange
      rate of wheat grown under well-watered and drought conditions.
AB  - The aim of this research was to determine the effects of timing and intensity of
      source reduction on grain yield of wheat under well-watered and drought stress
      conditions. A field experiment was conducted at the research farm of the
      Agriculture College, University of Tehran, Karaj, in 2003-2004. Drought stress
      was imposed when plants were at the second node stage by withholding watering and
      plants were re-irrigated when they showed signs of wilting or leaf rolling,
      particularly during the morning. Various intensities of leaf defoliation were
      performed at three growth stages: booting, anthesis and 20 days after anthesis.
      Flag leaf gas exchange parameters as well as chlorophyll content measurements
      were made 20 days after defoliation at each growth stage. Generally leaf removal
      appeared to stimulate an increase of net photosynthesis rate (p(n)) and stomatal
      conductance (g(s)) of the remaining flag leaf. With leaf removal, stability of
      the flag leaf chlorophyll content tended to increase. Neither grain yield, nor
      protein content were affected by defoliation. Interestingly, even removal of all
      leaves at anthesis stage did not reduce grain yield and grain protein
      significantly. Increased remobilization of stored photoassimilate, decreased
      maintenance respiration by source reduction and therefore enhanced
      photoassimilate partitioning toward grain and spike photosynthesis might be
      responsible for sustain grain growth in this condition.

PMID- 19090233
TI  - Effects of breed and progestin source on estrus synchronization and rates of
      fertility and fecundity in Iranian Sanjabi and Lori ewes.
AB  - A trial was conducted to evaluate the effects of FGA (Fluorogestone acetate) and
      CIDR (Controlled internal drug release) on the induction of estrus and pregnancy
      and fecundity rates of the Sanjabi and Lori sheep. A total of 360 Sanjabi and
      Lori sheep were randomly grouped into two treatments with intravaginal devices
      inserted for 13 days: Group FGA (40 mg FGA, n = 180) and Group CIDR (n = 180).
      All ewes received an i.m. injection of 400 IU eCG (equine chorionic
      gonadotrophin) at devices removal. Estrous was assessed by exposing all ewes to
      vasectomized rams at 12 h intervals. Cervical artificial insemination was
      performed 12 h after estrus onset. The overall estrus response was 72.5%. The
      source of progestin did not influence the efficiency of estrus response but a
      significant difference (p<0.05) was found between the breed groups (Lori: 88.6%,
      Sanjabi: 58.3%). Among the sheep that received either CIDR or FGA, estrus
      response was significantly (p<0.05) higher in the Lori (CIDR: 82.2%, FGA: 91.1%)
      than in the Sanjabi (CIDR: 64.4%, FGA: 52.2%) breed. The lambing and fecundity
      rates for all groups were 60.2% and 1.2 +/- 0.03, respectively. No significant
      differences in term of the lambing and fecundity rates were recorded between CIDR
      and FGA groups and among Lori and Sanjabi breed. The results of this study
      indicate the source of progestin or sheep breed did not influence the pregnancy
      and fecundity rates. The sheep breed influences the estrous response rate while
      the source of progestin did not affect the estrous response.

PMID- 19090234
TI  - An analysis of inputs cost for carp farming sector in 2001 in Iran.
AB  - Carp is widely sold and used in its fresh in Iran, however, recently a range of
      value additions may also be observed. It is essential to the sustainable
      development of a carp farm to know the production costs and their contribution.
      Warm-water fish farming is mainly based on common, silver, grass and bighead carp
      and the common carp and the three Chinese species are often reared in poly
      culture in Iran. Since, the 1970s carp farming has spread around the Caspian
      coast and farmed production reached a peak in 2006 with production of more than
      73,400 tons. A study of production, costs and profitability of carp farming
      sector was carried out to help clarify carp production costs and their difference
      with location in 2001. A total of 101 farms from the three main carp farming
      provinces, Guilan, Mazandaran and Khuzestan were randomly selected, classified
      and studied. The results of the survey showed that the various producer provinces
      have different cost structures. Overall, feed and fertilizer with the highest
      level of variation accounted for 23% of total costs, followed by seed and labor
      and salary with 23 and 17%, respectively. On average, benefit-cost ratio and the
      rate of farm income were closely related to location. This result suggests that
      farmers practice more efficiently and have better conditions in Mazandaran,
      followed by Guilan province.

PMID- 19090235
TI  - Phytochemical and toxicological studies of aqueous leaves extracts of
      Erythrophleum africanum.
AB  - The leaves of Erythrophleum africanum is known in the arid land of tropical
      Africa to posses toxicological properties. Phytochemical, acute and sub-acute
      evaluation of the possible toxicity risk of E. africanum aqueous leaves extracts
      were investigated in this study. Phytochemical constituents detected in the
      leaves extracts were saponins (1.16% w/v), cardiac glycosides, tannins (0.17 true
      tannins and 0.23% w/v pseudotannins), flavonoid glycosides, free flavonoids and
      alkaloids (4.34% w/v). The Lethal Dose (LD50) of the aqueous leaves extracts was
      greater than 3000 mg kg(-1) per os (orally) in albino rats. Sub-acute
      administration of the extract for 28 days resulted in significant (p<0.05)
      changes in some renal and liver indices at 3000 and 2000-3000 mg kg(-1) body
      weight, respectively. Histopathological lesions of the kidney and liver in form
      of moderate and marked infiltration with necrosis and perivascular lymphocytic
      cuff were observed. The observed lesions could be due to roles played by liver
      and kidneys in metabolism of xenobiotics and their elimination from the body.
      These investigations thus seem to indicate the toxic effects of the aqueous
      leaves extracts of E. africanum at 2000-3000 mg kg(-1). These could be attributed
      to the combined toxicity of the phytochemical constituents such as tannins,
      saponins, glycosides and alkaloids.

PMID- 19090236
TI  - Purification of a natural insecticidal substance from Cestrum parqui
      (Solanaceae).
AB  - Cestrum parqui is a shrub originating from Chile used in Tunisia as an ornamental
      plant. The toxicity of this plant was observed for the first time on the Desert
      Locust Schistocerca gregaria. It was shown that the toxicity of the plant is
      concentrated in the Crude Saponic Extract (CSE). In the present research we try
      to study chemically this fraction to isolate the active substances. The CSE was
      separated by column chromatography and the obtained fractions were biologically
      tested on Schistocerca larvae. We observed that only the fraction F9 was active,
      the separation of this fraction on preparative plates permits to isolate the
      active compound called S1. The tentative of structure elucidation of the natural
      substance S1 using 1H and 13C NMR shows that S1 is an heterosidic saponin.
      Structural modification of S1 structure provoke its activity lose.

PMID- 19090237
TI  - Variations in phytosterol composition during the ripening of Tunisian safflower
      (Carthamus tinctorius L.) seeds.
AB  - Phytosterols are bioactive components of all vegetable foods. Their most studied
      and outstanding properties being their cholesterol-lowering activity. This
      property has led to the development of functional foods enriched with plant
      sterols. In the present study, total and conjugated sterols of Tunisian safflower
      seeds were investigated and their kinetic of accumulation was surveyed during the
      ripening stages. The results obtained revealed that total and individual
      phytosterols were actively accumulated during the first stages of seed
      development then their levels decreased until full maturity. In the other hand,
      the sterol profile was marked by the predominance of beta-sitosterol during all
      ripening stages. As for Free Sterols (FS) and Esterified Sterols (ES), they were
      the major components and were actively accumulated from the beginning of seed
      development. Nevertheless, their amounts decreased at the end of maturity while
      Steryl Glycosides (SG) and acylated sterylglycosides (ASG) were practically
      stable during the ripening of seeds.

PMID- 19090239
TI  - Efficacy of Silicosec, a diatomaceous earth formulation against Tribolium
      castaneum (Herbst) (Coleoptera: Tenebrionidae).
AB  - Laboratory bioassays were carried out to evaluate the insecticidal efficacy of
      SilicoSec against 7- 14-days-old adults of Tribolium castaneum; old and young
      larvae with the mean weight of 3.4 +/- 0.1 and 0.6 +/- 0.1 mg, respectively at 27
      degrees C and 55 +/- 5% r.h in the dark. Wheat treated with four dose rates of
      SilicoSec with three replications. Adult's mortality was measured after 2, 7 and
      14 days of exposure. After 14 days mortality count, all adults were removed and
      samples retained under the same conditions for a further 60 days to assess
      progeny production. In the case of larvae, mortality was counted after 1, 2 and 7
      days. After 2 days of exposure no concentration achieved 11% mortality for
      adults, however; adult's mortality exceeds 89.65% when exposed for 7 days to
      SilicoSec. Mortality of old and young larvae at 0.6 g kg(-1) after 2 days were
      28.88 and 22.22%, respectively and exceed to 60.71 and 69.04% at longer exposure
      of 7 days. Results indicated that mortality of T. castaneum was influenced by
      interval exposed to wheat treated with SilicoSec and over this exposure; the
      increases in application rate of SilicoSec had significant effect on the
      mortality. Young larvae of red flour beetle were more sensitive to SilicoSec than
      old larvae and adults were more tolerant. Reproductive potential of adults in the
      treated wheat was suppressed when compared with untreated wheat. The high
      retention level of SilicoSec (78.62%) was noted in wheat kernels.

PMID- 19090238
TI  - Effects of drought stress on protective enzyme activities and lipid peroxidation
      in two maize cultivars.
AB  - Response of antioxidative defense system to drought stress was studied in two
      cultivars of maize differing in sensitivity to drought. The six-days-old
      seedlings were transferred in to different concentrations of polyethyleneglycol
      (PEG) 6000 as drought stress treatment. After 24 h treatment with PEG 6000 an
      increase was observed in protective enzymes, MDA content and electrolyte leakage.
      Under drought stress the activities of protective enzymes in roots and shoots
      increased sharply. This increase in 704 variety was higher than 301 variety. The
      protective enzyme activities in roots were lower than those in shoots. The
      content of malondialdehyde (MDA) increased according to severity of water stress.
      The content of MDA in roots was lower than in shoots. The electrolyte leakage
      increased greatly in drought stress, too. Increase of MDA content and electrolyte
      leakage in 704 variety were higher than 301 variety.

PMID- 19090240
TI  - Phytotoxicity of methyl tert-butyl ether to common bean (Phaseolus vulgaris L.)
      plants.
AB  - The current investigation was conducted to report on the phytotoxicity of methyl
      tert-butyl ether (MTBE) to common bean (Phaseolus vulgaris L. cv. Nebraska)
      plants. The two-week-old potted plants were subjected to four weekly soil
      applications of aqueous MTBE concentrations (0, 1, 10, 25 and 50 ml L(-1)). The
      root growth, flower and pod development were more sensitive to MTBE treatments;
      while, stem growth and photosynthetic pigments were more persistent to the
      toxicity of MTBE. The total number of protein bands/lane in SDS-PAGE protein
      profile was reduced by MTBE treatments. Two proteins of molecular weight 53.83
      and 30.96 kDa were newly synthesized at the highest concentrations (25 and 50 ml
      L(-1)) of MTBE; while the syntheses of other proteins were completely inhibited
      with varying sensitivity to MTBE concentrations. The toxicity of MTBE
      concentrations caused progressive collapsing of epidermal and cortical tissues of
      the plant roots. MTBE is quite toxic to crop plants in contaminated soils of
      agricultural systems.

PMID- 19090241
TI  - Effects of aspirin and celecoxib on rigidity in a rat model of Parkinson's
      disease.
AB  - Parkinson's disease (PD) is a degenerative neurodopaminergic disease in
      nigrostriatum pathway of human and is responsible for most of the movement
      disorders. Increasing evidence suggests that an inflammatory reaction accompanies
      the pathological processes caused by Cyclooxygenase (COX) seen in many
      neurodegenerative disorders, including PD and according to the recent researches
      chronic use of Non-Steroidal Anti-Inflammatory Drugs (NSAIDs) decreases the risk
      of PD in human. In the study the rat left Substantia Nigra Pars Compacta (SNc)
      have been destroyed using electrical lesion (1 mA; DC; 8 Sec) to induce PD model.
      Then aspirin (30, 60 mg kg(-1)) and celecoxib (4, 8 mg kg(-1)) have been
      administrated orally to parkinsonian rats. When the animals were suffered to PD
      Murprogo's Method evaluated the rigidity ofparkinsonian rats. Both selective COX
      2 inhibitor (celecoxib) and non-selective COX-2 inhibitor (aspirin) decreased the
      rigidity of parkinsonian rats p<0.05 but rigidity recovery after administration
      the selective COX-2 inhibitor was more than non-selective COX-2 inhibitor. These
      findings are additional pharmacological information which has suggested the use
      of NSAIDs as alternative way to treat the rigidity of PD.

PMID- 19090242
TI  - Study of some physiological changes in sugar beet cv. 7233 in the presence of
      sugar beet cyst nematode, Heterodera schachtii and an antagonistic sterile fungus
      StFCh1-1 in the rhizosphere condition.
AB  - In this study, several physiological parameters of inoculated sugar beet plants,
      with the beet cyst nematode, Heterodera schachtii, were evaluated in the presence
      of an antagonistic sterile fungus StFCh1-1 in the rhizosphere condition. The
      sugar beet plant used in this bioassay was a multigerm cultivar, 7233, which is
      sensitive to the beet cyst nematode and has been adapted to cultivate in
      temperate and cool regions of the sugar beet production areas of Iran. In this
      regard a potent bioassay was conducted in the sterile glass tubes (20 x 3 cm phi
      ) containing 30 g autoclaved soil and planted with a sterile germinated seed of
      sugar beet, totally in 24 tubes. The seedling of sugar beet plant at four leaves
      stages in two treatments (nematode and nematode + fungus) was inoculated with 50
      disinfected beet cyst nematodes. As a standard procedure the bioassay composed of
      four treatments including: fungus, nematode, nematode + fungus and untreated
      control. Two months after nematodes' inoculation some physiological parameters of
      plants were measured including: total chlorophyll, potassium and biomass. The two
      treated plants with nematode and nematode plus fungus showed significant decrease
      in biomass and chlorophyll contents but treatment with fungus alone showed no
      significant differences in the biomass and chlorophyll content of plants in
      comparison with the control. The potassium content of shoots in the invaded sugar
      beet plants was lowest, but it was highest in the roots. These changes might be
      indication of adaptive osmoregulation or acclimation responses in plants due to
      the nematodes as bio-stressors through the increase of metabolites and solutes.
      Also, these results confirmed that in plants inoculated with nematode plus
      fungus, a few number of female of nematodes were developed due to the
      antagonistic effects of sterile fungus StFCh1-1. Meanwhile, the fungus didn't
      have any detrimental effect on biomass, chlorophyll content and potassium in
      leaves of sugar beet cv. 2733 and it is safe to use as a biocontrol agent against
      Heterodera schachtii.

PMID- 19090243
TI  - Effect of variable rates of gypsum application on wheat yield under rice-wheat
      system.
AB  - A field experiment was initiated during 2005-2006 to study the effect of gypsum
      application on rice and subsequent wheat crop. The direct, residual and
      cumulative effects of gypsum were also noticed under rice-wheat system. The
      gypsum was applied as 0, 1 and 2 t ha(-1) with the basal dose of N, P2O5, K2O as
      120, 90 and 60 kg ha(-1) to both crops. Rice variety IRRI6 and wheat variety
      Naseer 2000 were planted in Randomized Complete Block Design with three
      replications in a permanent layout. The soil samples were collected from both
      crops before earing to study P and K concentrations. The rice yield was
      significantly affected by gypsum application that ranged from 4807-5472 kg ha(
      1). The highest rice yield was recorded by the application of 2.0 t gypsum ha(-1)
      with an increase of 13.8% over control. Similarly all the yield components like
      number of panicles m(-2), panicle length, plant height and 1000 grain weight were
      also significantly affected by gypsum application. The wheat grain yield ranged
      from 2598 to 4304 kg ha(-1). The cumulative application of 1 and 2 t gypsum ha(
      1) increased the wheat yield by 25.25 and 65.66% over check, respectively. The
      direct and residual application of 2 t gypsum ha(-1) gave an increase of 46.80
      and 15.05% over the check, respectively. The application of gypsum significantly
      affected the P and K that ranged from 4.50-7.50 and 4.70-9.32 mg kg(-1) P while
      70-110 and 78-112 mg kg(-1) K in rice and wheat, respectively.

PMID- 19090244
TI  - Cigarette smoking and the risk of male infertility.
AB  - In this research we investigated the effect of cigarette smoking on sperm
      parameters both before and after swim-up. Semen sample provided from fertile
      smoker (n = 25), fertile nonsmoker (n = 21), infertile smoker (n = 23) and
      infertile nonsmoker men (n = 32). Semen analysis was performed manually according
      to the World Health Organization (WHO) standards guidelines. Present research
      showed that sperm parameters quality in smoker men was approximately lower than
      nonsmoker men. As well as present research showed that cigarette smoking has dose
      dependent effect on sperm parameters, but this effect was not significant.
      Therefore, it appears that cigarette smoking is associated with reduced sperm
      quality and the risk of idiopathic male infertility in smoker men.

PMID- 19090245
TI  - Effect of Urtica dioica on morphometric indices of kidney in streptozotocin
      diabetic rats--a stereological study.
AB  - The aim of the present study was to investigate the effect of Urtica dioica on
      Morphometric indices of kidney in diabetic rats. Thirty male adult albino wistar
      rats of 125-175 g divided into control, diabetic and Urtica dioica treatment
      groups. In treatment Group, diabetic rats received 100 mg kg(-1) daily
      hydroalcoholic extract of U. dioica intraperitoneally for 4 weeks. After the
      animals had been sacrified, the kidneys were removed and fixed by formaldehyde,
      cut horizontally into 1 mm slices and processed, Stained with H and E.
      Stereological study performed using light microscope and the image projected on a
      table of olysa software. Cavalieri principle was used to estimate the volume of
      cortex, medulla and whole kidney. All the grouped data statistically evaluated
      using Student's t-test, expressed as the Mean +/- SE. Ration of kidney
      weight/body weight in diabetes (0.51) and diabetes-extract group (0.67) were
      higher then control group (0.42). Ratio of kidney volume/body weight in diabetes
      (350) and diabetes-extract group (348) were higher then control group (323).
      Volume Ratio of cortex/medulla in diabetes-extract group (1.65) was higher then
      control (1.34) and diabetes group (1.33). Glomerular area and diameter and
      proximal tubule diameter in diabetes-Extract group was higher than control and
      diabetes groups. This study revealed that Urtica dioica has no effect on renal
      morphometric indices in induced diabetic rats.

PMID- 19090246
TI  - Effect of sodium chloride on establishment of callus and organogenesis in
      Brassica napus L.
AB  - In order to produce salt tolerant canola (Brassica napus L.) plants hypocotyl
      segments of its that were excised from 7-days-old-seedlings cultured in MS medium
      with various concentrations of PGRs (NAA, IBA, 2, 4-D, KN and BA) and sodium
      chloride. The best media for induction and growth of callus (6 mg L(-1) 2, 4-D
      and 2 mg L(-1) BA), production of adventitious shoots (1 mg L(-1) IBA and 1 mg L(
      1) BA) and roots (1 mg L(-1) NAA and 0.5 mg L(-1) KN) were determined. Then
      explants cultured in these media plus 0-273.53 mM L(-1) sodium chloride. Explants
      in these media established and in some of concentrations of sodium chloride
      (68.37-102.56 mM L(-1)) produced calli and adventitious shoots and roots better
      than the same media but free from sodium chloride. This finding suggests that
      somaclonal variation can yield stable-tolerant canola plants.

PMID- 19090247
TI  - Effect of aqueous extract of Azadirachta indica (Neem) leaves on germination and
      seedling growth of Vigna radiata (L.).
AB  - This research was carried out to evaluate the allelopathic effect of leaves
      aqueous extract of Azadirachta indica on germination and seedling growth of Vigna
      radiata. Different methods were used to preparing leaves aqueous extract.
      Germination percentage and seedling growth of V. radiata significantly decreased
      gradually as the concentration of the aqueous leaves extracts of A. indica
      increased in comparison with water control. Severe toxicity was observed at high
      concentrations and moderate toxicity at low concentrations in comparison with
      water control. Aqueous leaves extract significantly inhibited root length more
      than shoot. These results indicated that some kind of inhibitor(s) was the
      responsible agent for the phytotoxic effect of A. indica on germination and
      seedling growth of V. radiata.

PMID- 19090248
TI  - The prevalence of asymptomatic bacteriuria in long term care facility residents
      in Shiraz, Southwest Iran: a cross-sectional study.
AB  - This study detected the prevalence of Asymptomatic Bacteriuria (ABU) in residents
      of long term care facilities in Shiraz, Southwest Iran. From 100 residents aged
      between 55- 95-years-old, aseptically collected mid-stream urine samples
      underwent culture and antimicrobial sensitivity analysis. The prevalence rate of
      ABU was 53% with 95% CI 43.2 to 62.8% which was higher than that for elsewhere.
      ABU was observed more frequently in the females (57.7%), elderly (89%) and
      diabetic elderly subjects (72.3%). ABU in the diabetic elderly was also more than
      that for non-diabetic elderly subjects (p<0.05). E. coli was the most common
      bacteria isolated. Resistance rate of gram positive bacteria to penicillin and
      cefazolin were 100% and those for tetracycline and vancomycin were 72.2 and
      66.7%, respectively. The most gram negative bacteria were sensitive to
      aminoglycosides. Present results showed a higher prevalence of unknown ABU in the
      residents of nursing homes in Shiraz, Iran as compared to other countries in the
      world. It might be due to lack of efficient institutional care and uncontrolled
      diabetes mellitus or other factors influencing immunity.

PMID- 19090249
TI  - Comparison of antioxidant and free radical scavenging activities of the essential
      oils from flowers and fruits of Otostegia persica Boiss.
AB  - The aerial parts of the endemic plant of Otostegia persica Boiss. in two
      different stages of flowering and fruiting were hydro-distilled to extract oils
      in the yields of 0.3 and 0.15% (v/w), respectively. The oils were analyzed by GC
      and GC/MS. Twenty-eight and thirty-one components were identified, representing
      97.59 and 94.61% of the oils, respectively. The main compounds of the essential
      oil flowers (EOFL) were alpha-pinene (17.21%), 1-octen,3-ol (13.44%) and cubenol
      (7.27%), whereas diisooctyl phthalate (45%) and hexadecanoic acid (11.07%) were
      the major constituents of the essential oil of the fruits (EOFR). The oils were
      screened for their possible antioxidant activities by two complementary test
      systems, namely DPPH free radical-scavenging and ammonium thiocyanate. In both
      tested systems, EOFL exerted greater antioxidant and radical scavenging activity.
      In the first case, EOFL exerted antioxidant activity with an IC50 19.8 +/- 1.8
      microg mL(-1) almost similar to BHA and ascorbic acid (15.2 +/- 1.1 and 17.4 +/-
      1.3), respectively. In the ammonium thiocyanate system, the inhibition rate of
      oxidation of linoleic acid for EOFL was estimated 93.5 +/- 2.8. The higher
      activity of this oil in comparison to EOFR may be attributed to its high content
      of monoterpenes, especially oxygenated ones in the oil of the flowers.

PMID- 19090251
TI  - Evaluation of maize yield in an on-farm maize-soybean and maize-Lablab crop
      rotation systems in the Northern Guinea Savanna of Nigeria.
AB  - An attempt was made to solving the problem of shortfall of fertilizer to maize
      production in the Northern Guinea Savanna (NGS) of Nigeria by harnessing the
      potentials of legume/cereal crop rotation in on-farm trials. The yield of maize
      that succeeded two soybean varieties and Lablab in a two-cycle of soybean/maize
      and Lablab/maize crop rotation in NGS Nigeria was assessed in researcher-managed
      and farmer-managed plots. Though maize that followed the soybean received between
      5 kg N ha(-1) from improved soybean variety (TGx 1448-2E) and 17 kg N ha(-1) from
      farmer soybean variety (Samsoy-2) as N balance, this did not significantly (p =
      0.05) affect the maize yields. The soybean shed 90-100% of its leaves at
      physiological maturity which resulted in about 110 kg N ha(-1) N uptake. This
      source of N might be one of the factors responsible for the increase in maize
      yield that followed soybean (20 to 24%) compared with continuous maize yield
      plot. Maize yield in previous Lablab plot was significantly (p = 0.05) higher
      than in all other treatments. Maize yield in farmer-managed plot ranged between
      0.13 and 4.53 t ha(-1), maize yield in researcher-managed plot was over 200%
      higher than maize yield in farmer-managed plot because of poor crop management on
      the part of the farmer.

PMID- 19090250
TI  - Influence of auxins combinations on accumulation of reserpine in the callus of
      Rauvolfia tetraphylla L.
AB  - Reserpine is a monoterpene indole alkaloid used to treat hypertension because of
      its hypotensive property and psychiatric disorders because of its tranquilizing
      effect. Protocol has been standardized to enhance the synthesis of reserpine in
      leaf derived calli of Rauvolfia tetraphylla L. by adjusting the auxins
      combinations in the medium consisting of MS nutrient salts and B5 vitamins.
      Auxins such as naphthalene acetic acid (NAA), indole-3-acetic acid (IAA) and
      indole-3-butyric acid (IBA) were used in 1-5 microM concentration along with 9
      microM concentration of 2,4 dichlorophenoxy acetic acid (2,4-D), which was found
      suitable for callus induction. The combination of (2,4-D) with NAA had been
      proved to accumulate maximum amount of reserpine followed by 2,4-D with IBA. The
      IAA with 2,4-D combination yielded very less amount of reserpine than the other
      combinations and 9 microM 2,4-D alone. The results suggest that there may be
      synergetic effect of NAA with 2,4-D and IBA with 2,4-D for increase in the
      biomass and reserpine accumulation and antagonistic effect of IAA with 2,4-D for
      the above said factors in the callus.

PMID- 19090252
TI  - Study on the role of common weeds in survival of Verticillium dahliae the causal
      agent of cotton wilt disease.
AB  - This study was carried out to investigate the roles of common weeds in the
      survival of Verticillium dahliae and the incidence of cotton wilt disease in
      Moghan and Neishabour area of Iran during 2003-2005 cropping seasons. The design
      of the experiment was Randomized Complete Blocks (RCB) with ten treatments (No.
      of weeds) and four replications (No. of cotton fields). Populations of V. dahliae
      in the roots of weeds and their surrounding soil was determined every year and
      were compared in different treatments. The cotton wilt disease index was also
      evaluated in different fields in each experimental site. Results indicated that
      the fungal population was variable depending on weed species, experimental site
      and the year of study. In general, Pigweed (Amaranthus retroflexus), Nightshde
      (Solanum nigrum), Spiny cockleburr (Xanthium spinosum) and common purslane
      (Portulaca oleraceea) showed the highest fungal populations in their roots and
      surrounding soil. Disease index in Moghan cotton fields in different years varied
      and were higher than Neishabour fields.

PMID- 19090253
TI  - Comparison of plasma cardiac Troponin I and cardiac enzymes in haemodialysis
      patients of Gorgan (south east of Iran).
AB  - The objectives of this study were to evaluate the effect of haemodialysis on
      plasma Cardiac Troponin I and cardiac enzymes before and after the dialysis
      process. Twenty two patients with Chronic Renal Failure (CRF) disease who were
      haemodialyzed at 5th Azar hospital of Gorgan Dialysis Center were recruited for
      this study (2005). The patients do not have coronary heart disease. Plasma
      cardiac enzymes showed no significant difference in the post dialysis group when
      compared with predialysis. Plasma levels of Cardiac Troponin I in 12
      haemodialyzed patients were significantly increased in the postdialysis group
      when compared with predialysis, whereas plasma level of Cardiac Troponin I in 10
      haemodialyzed patients were undetectable (less than 0.1 microg L(-1)). The
      observation of meaningful increasing level of plasma Cardiac Troponin I in the
      haemodialyzed patients after the process of dialysis shows that Cardiac Troponin
      I is highly specific marker for Acute Myocardial Infarction (AMI) when compared
      with other cardiac enzymes and is particularly useful for detecting AMI in
      chronic renal failure and haemodialysis patients which can prevent sudden
      cardiovascular abnormality and sudden silent myocardial infarction in these
      patients.

PMID- 19090254
TI  - Biosorption of copper, cobalt and nickel by marine brown alga Sargassum sp. in
      fixed-bed column.
AB  - The biosorption of copper, cobalt and nickel by marine brown alga Sargassum sp.
      were investigated in a fixed-bed column (temperature = 30 degrees C; different
      pH). Langmuir and Freundlich sorption models were used to represent the
      equilibrium data. The maximum Cu2+ uptake was obtained at pH 4 and the optimum
      Co2+ and Ni2+ uptake were at pH 7. Different dosage of biosorbent did not have an
      effect on the results, but the 3.5 and 5 g of biosorbent were shown higher
      uptake. The metal removal rates were rapid, with about 80% of the total
      adsorption tacking place within 40 min.

PMID- 19090255
TI  - Antibacterial activity and chemical constitutions of essential oils of Thymus
      persicus and Thymus eriocalyx from west of Iran.
AB  - The essential oils of Thymus persicus and Thymus eriocalyx were collected in
      Lorestan province, west of Iran and were examined by GC/MS and bacteriological
      tests. Twenty seven compounds representing 92.095% of T. persicus and 99.77% of
      Thymus eriocalyx essential oils were identified. The major constituents of T.
      persicus were thymol (10.71%), carvacrol (25.71%), gamma-terpinene (5.63%), alpha
      pinene (1.14%), beta-pinene (1.02%), limonene (11.65%) trans-sabinene hydrate
      (7.78%) and 1-borneol (4.07%) and the major compounds of T. eriocalyx. were 1, 8
      cinole (3.07%), L-linalool (1.01%), thymol (66.34%), caryophyllene oxide (2.96%)
      and carvacrol (7.5%). The oils also were examined for antibacterial activities
      against 6 standard bacteria by the broth microdilution and disc diffusion
      methods. They exhibited significant antibacterial activities against
      Staphylococcus aureus (MIC =1 : 235, MBC =1:20), Escherichia coli (MIC = 1:320,
      MBC =1:80) and Pseudomonas aeroginosa (MIC = MBC = 1:1280). The results were
      compared with control antibiotics.

PMID- 19090257
TI  - Comparative production of 6-aminopenicillanic acid by different E. coli strains
      and their acridine orange (AO) induced mutants.
AB  - The present study was conducted to see the difference in production of 6-APA I)
      between wild strains of E. coli collected from local environment and their
      acridine orange (AO) induced mutants and ii) between mutants and E. coli strains
      (ATCC 11105 and ATCC 9637) of American Type Culture Collection (ATCC) used
      commercially for enzymatic production of 6-APA. The optimum conditions for
      bioconversion were standardized and 6-APA was obtained in crystalline form.
      Relative PGA activity of local and foreign E. coli strains varied significantly
      with the highest being 12.7 in mutant strain (BDCS-N-M36) and the lowest 4.3 mg 6
      APA h(-1) mg(-1) wet cells in foreign strain (ATCC 11105). The enzyme activity
      exhibited by mutant strain (BDCS-N-M36) was also two folds higher compared to
      that in wild parent BDCS-N-W50 (6.3 mg 6-APA h(-1) mg(-1) wet cells). The overall
      production of 6-APA and conversion ratios ranged between 0.25-0.41 g of 6-APA per
      0.5 g of penicillin G and 51-83%, respectively. Maximum conversion ratio (83%)
      was achieved by using crude cells of mutant strain (BDCS-N-M36) which is the
      highest value ever reported by crude cells on a shake-flask scale whereas
      reported 6-APA production by immobilized cells is 60-90% in batch and continuous
      systems. Results are being discussed with reference to importance of local
      bacterial strains and their significance for industrially important enzymes.

PMID- 19090256
TI  - Effects of different concentrations of 2,4-D and BAP on somatic embryogenesis
      induction in saffron (Crocus sativus L.).
AB  - To optimize an in vitro protocol for propagation of saffron through somatic
      embryogenesis, effects of various concentrations of 2,4-D ( 0, 0.25, 0.5, 1, 2, 4
      and 8 mg L(-1)) in combination with BAP (0, 0.25, 0.5, 1, 2, 4 and 8 mg L(-1))
      were studied. Surface-sterilized corms were cut transversally into equal portions
      and the upper or lower parts were used separately as explants. All treatments
      were maintained in the darkness at 24 +/- 2 degrees C. After 70 days, the first
      globular embryos were observed and the number of embryos on each explant reached
      to its maximum 3 months after culture. Statistical analysis showed that there
      were significant differences between treatments regarding the number of embryos
      induced on each explant. The most effective treatment was 2.0 mg L(-1) 2,4-D +
      1.0 mg L(-1) BAP for both types of explant (inducing 6.5 +/- 1.3 and 35.95 +/-
      4.9 embryos on each explant for the upper and lower parts, respectively). The
      average percentages of explants showing embryogenic response were 33.3 and 93.3%
      for the upper and the lower part of corm tissue respectively in this treatment.
      Complementary studies are in progress to optimize maturation and germination
      stages of these somatic embryos.

PMID- 19090258
TI  - Bovine epididymal sperm morphology obtained from caput, corpus and cauda
      epididymides.
AB  - To investigate the proportion of normal sperm cells in bovine epididymis, bovine
      testicles (n = 50), obtained from a local slaughterhouses, epididymides were
      incised and sperm cells were transferred into slide glasses where eosin nigrosin
      stain was applied either in the place or in laboratory. When sperm were stained
      in slaughterhouse, 88% of caput epididymal sperm were alive; 9% without
      protoplasmic droplet (NPD), 10.2 and 68.8% had distal (DD) and Proximal Droplets
      (PD), respectively. Of dead sperm, 10.4% were NPD and 0.33 and 1.27% had DD and
      PD, respectively. Of corpus epididymal sperm, 77.2% were alive of which 14.7%
      were NPD, 58.3 and 4.2% had DD and PD, respectively. Of dead sperm, 20.4% were
      NPD and 2.2 and 0.2% had DD and PD, respectively. When spermatozoa were stained
      in laboratory, 71.7% were alive of which 17.4% were NPD, 49.7 and 4.6% had DD and
      PD, respectively. Of dead sperm, 23.1% had no droplet and 4.21 and 0.99% were DD
      and PD, respectively. The proportion of live spermatozoa from caudal epididymis
      was 86.1%, of which 9.9% were NPD, 68.3 and 7.9% had DD and PD, respectively. Of
      dead spermatozoa, 10.1% had no droplet and 3.3 and 0.5% had DD and PD,
      respectively. No significant difference observed between different parts of
      epididymis and also between slaughter house staining and laboratory staining of
      sperm cells. Data showed that approximately all parts of epididymis contained
      similar status of live sperm cells and the sperm cells containing protoplasmic
      droplets.

PMID- 19090259
TI  - A survey of seasonal infestation with Przhevalskiana larvae in slaughtered goats
      and sheep in South-Western Iran.
AB  - In this research slaughtered sheep and goats were investigated during August 2003
      July 2004 at a slaughterhouse in Masjed-Soleyman, South-Western Iran. The number
      of infested animals with Przhevalskiana larvae and their age and sex was
      recorded. Collected larvae from infested animals were stored in Alcohol-Glycerin
      solution and were studied to determine their morphological properties and
      species. The data was analyzed by the chi-square test. Rate of infestation was
      0.2 and 5.3% in sheep and goats, respectively. Infestation rate in male and
      female goats and sheep was significantly different (p<0.05). Prevalence of
      hypodermosis in sheep was significantly different in spring and winter, while
      infestation prevalence in goats was significantly different in four seasons of
      the year. Myiasis was seen more frequent in 2-3 and 1-2-year-old age groups of
      sheep and goats, respectively. The causative agents of goat and sheep
      hypodermosis were Przhevalskiana aegagri and Przhevalskiana crossii. The onset of
      fly activity was from late June to mid July.

PMID- 19090260
TI  - Combined compost and vermicomposting process in the treatment and bioconversion
      of sludge.
AB  - Traditional thermophillic composting is commonly for treatment of sludge. A
      related technique as vermicomposting process, using earthworms to breakdown
      sludge, is also becoming popular. These two techniques have their inherent
      advantages and disadvantages. The combined approach suggested in this study to
      enhance the overall process and improve the products qualities. Two systems,
      vermicomposting and combined compost-vermicomposting processes, have been
      investigated in this study. The sludge used in this study was obtained from the
      drying beds of South Isfahan wastewater treatment plant. The sludge mixed with
      sawdust to provide C/N ratio of 25/1. Eisenia fetida was the species of
      earthworms used in the vermicomposting processes. The results obtained indicate
      reduction in the amount of volatile solids, total carbon and C/N ratio with the
      vermicompost age, which indicates the reduction in the biodegradable organic
      content and mineralization of sludge. Also increase in phosphorus concentration
      by the end process because of mineralization of organic matter. The results
      indicate that, a system that combines the two mentioned processes not only
      shortens stabilization time, but also improves the products quality. Combining
      the two systems resulted in a product that was more stable and homogenous; the
      product could meet the pathogen reduction requirements.

PMID- 19090261
TI  - Comparison of egg production between two quail strains and their reciprocal
      crosses.
AB  - Hen Day (H-D) and Hen-Housed (H-H) egg production for 135 day period compared in
      two quail strains and their reciprocal crosses in two separate trails. At the
      first trail in two hatches 180 Japanese quail (Coturnix japanese) and 180 Range
      quail (Coturnix ypisilophorus) were reared in two different spaces [litter with
      sawdust (250 x 200 x 230 cm) and one-tier cage (50 x 50 x 70 cm)]. The 130-day
      period production was measured from date of first egg for each female. Strain
      difference were not significant for H-D (p>0.05), but there were significant
      difference for H-H (p<0.01). Also H-D and H-H were significantly different by
      space of variations (p<0.01). Japanese quails with H-H 72.42 +/- 0.65% were
      significantly higher than Range quail with 62.68 +/- 1.07. At the second trail in
      two hatches 800 quails include four groups: 1--Japanese quails, 2--Range quails,
      3--Hybrid 1 (R male x C female). 4--Hybrid 2 (C male x R female) were reared in
      four-tier cage from 28 days of age to experiment end. H-D and H-H of four groups
      were significantly different (p<0.01). Japanese quails with H-D 77.39 +/- 1.23%
      were the highest in four groups, but H-D between Japanese quail and H2 was not
      significantly different (p>0.05). H-D were not affected by hatch effects
      (p>0.05), but H-H at second hatch was significantly higher than first hatch. Egg
      weights were obtained with sample 35 eggs which randomly were selected at 70th,
      115th and 175th days of age production for Japanese quails, hybrid 1, hybrid 2
      and Range quails 11.16 +/- 0.16, 10.92 +/- 0.17, 10.61 +/- 0.11 and 11.06 +/-
      0.12 g, respectively.

PMID- 19090262
TI  - Household waste management in Mashad: characteristics and factors influencing on
      demand for collecting services.
AB  - In order to characterize household waste management system in Mashad (Northeast
      of Iran) and evaluate factors which affect on demand for waste collecting
      services, a field survey was conducted. One hundred ninty eight families were
      selected according to classified randomized sampling system and data on their
      socio-economic characters including home area, type (apartment versus other
      types) and tenure (private versus rental), education, separating solid and
      organic wastes, family size and income were gathered using questionnaires and
      direct interview. Results showed that three variables including staying at home
      during day, home type and family size explained 21% of variations of demand for
      waste collecting services. The study emphasized on components of pricing and
      economic motivations as well as education and socio-economic factors for
      decreasing of household waste production. Suggestions have been presented for
      improving the efficiency of waste management system in Mashad.

PMID- 19090263
TI  - Concentration of heavy metals in different tissues of Astacus leptodactylus from
      Aras dam of Iran.
AB  - Due to different human activities in the vicinities of Aras dam, various
      pollutants such as heavy metals are entered into the reservoir and thus polluting
      the aquatic ecosystem. As a result, this heavy metal is accumulated in the
      tissues of Astacus leptodoctylus, which is considered as one the abundant species
      of crayfish that has got important food values and is of economic importance due
      to its export to other countries. In this research, the bioaccumulation of heavy
      metals in different tissues of this animal is taken into consideration. The
      concentration of Fe, Cu, Zn, Mn, Pb, Ni, Co and Cr among the tissues of female
      and male Astacus leptodactylus has been determined. The highest concentration of
      Cu and Fe was found in the gills and the highest level of Zn was found in
      hepatopancreas. Besides, the highest Mn concentration was recognized in
      exoskeleton. Furthermore, no significant difference was found between the male
      and female crayfish in the concentration of the heavy metals in their tissues,
      except for the concentration of some of the metals such as Fe in some of the
      tissues such as hepatopancreas.

PMID- 19090264
TI  - Detection of Ureaplasma urealyticum in semen of infertile men by PCR.
AB  - Ureaplasma urealyticum is a causative agent ofnon-gonococcal urethritis,
      prostatitis, epididymitis and infertility. The organism is more common in
      partners of infertile than fertile marriages. U. urealyticum infections not only
      jeopardize fertility but also pose a risk for infertility treatment and resulting
      pregnancies. The purpose of this study was to determine the prevalence of U.
      urealyticum in semen of infertile and healthy men by Polymerase Chain Reaction
      (PCR). Semen samples were obtained from infertile patients and healthy control
      and were subjected to the routine andrological analysis and PCR. DNA was
      extracted by Cadieux method and analyzed by PCR protocol with species-specific
      primers for U. urealyticum (urease gene). U. urealyticum was detected
      significantly by PCR in 12 of 100 (12%) semen specimens from infertile patients
      and in 3 of 100 (3%) healthy men. The volume of semen fluid, concentration of
      sperm cells and sperm cell with normal morphology were significantly decreased in
      infertile men. In the group of infertile patients with PCR positive for U.
      urealyticum the volume, count and morphology of semen samples were lower than in
      the infertile patients with PCR negative results.

PMID- 19090265
TI  - The astrocytes number in different subfield of rat's hippocampus in reference
      memory learning method.
AB  - In this study with usage of morris water maze and reference memory technique, we
      used 10 male albino wistar rats. Five rats in control group and 5 rats in
      Reference memory group. After histological preparation, the slides were stained
      with PTAH staining for showing the Astrocytes. Present results showed significant
      difference in astrocytes number in CA1, CA2 and CA3 area of hippocampus between
      control and reference memory group. The number of astrocytes is increased in
      reference memory group. Then we divided the hippocampus to three parts: Anterior,
      middle and posterior and with compare of different area (CA1, CA2 and CA3) of
      hippocampus, we found that the increase of astrocytes number in posterior two
      third of CA2 and CA3 is more than of it's number in the anterior one-third.

PMID- 19090266
TI  - Prevalence of pediculosis and scabies in the prisoners of Bandar Abbas, Hormozgan
      province, Iran.
AB  - The increasing prevalence of active pediculosis and scabies among prisoners
      prompted us to conduct a head louse and scabies prevalence survey among prisoners
      in the Bandar Abbas, Hormozgan province, Iran. During the study, 67 patients with
      skin disorders were found. Among the doubtful patients who were considered 38
      patients (57%) indicated Sarcoptes scabiei, 6 patients (9%) were indicated lice
      and 23 patients (33%) were set aside for more studying and specialized tests.
      Contamination rates were 18.4, 10.5 and 10.5% in the youths, drug abusers and
      kitchen units, respectively. Adults, foreigners and quarantine units were
      contaminated 7.9, 5.3 and 5.3%, respectively. In cheque and military units, no
      contamination was observed because of the higher hygienic status. Morbidity rate
      in the individual and technical units was 2.5%. The highest and the least
      morbidity rates were observed among 20-29 year age group (55.2%) and over 50 year
      age group (2.6%). The average and the mean ages of the 38 patients that
      contaminated to Sarcoptes scabiei was 29 +/- 8 and 28 years, respectively. The
      least and the highest contamination ages were 18 and 59 years, respectively. The
      affirmative Sarcoptes scabiei cases in the different units indicated that the
      general units had the most morbidity percentage because there were many prisoners
      with different cultural backgrounds (26.3%).

PMID- 19090267
TI  - Antibody titers against canine distemper virus in unvaccinated rural dogs from
      Ahvaz, Iran.
AB  - The purpose of this study was to evaluate the prevalence of antibodies to Canine
      Distemper Virus (CDV) in unvaccinated rural dogs without known immunization
      status and to assess risk factors for infection by means of indirect
      immunofluorescent assay (IFA), in Ahvaz district, southwest of Iran. Serum
      samples were randomly collected from 97 healthy dogs 6 months and older from
      villages around Ahvaz city between 2004 and 2005. Dogs were grouped by age and
      sex to determine whether these factors were associated with antibody titers,
      using Fisher's exact test. Seroprevalence to CDV antibodies in these dogs were
      17.52% indicating that this virus is present in the ecosystem. Also there is
      evidence of previous natural exposure to CDV. Prevalence of antibodies to CDV did
      not differ between sexes or ages. Rural dogs are abundant in the ecosystem of
      area and interact with other species of wild carnivores and domestic animals in
      ways that could encourage disease transmission. Therefore the role of rural dogs
      in the epizootiology of CDV in both urban dogs and wildlife needs to be further
      explored.

PMID- 19090268
TI  - Study the effect of hexavalent chromium on some biochemical, citotoxicological
      and histopathological aspects of the Orechromis spp. fish.
AB  - In nature chromium occurs in divalent, trivalent and hexavalent forms. Hexavalent
      chromium predominates over the trivalent form in natural waters. Knowledge of
      acute toxicity of a xenobiotic often can be very helpful in predicting and
      preventing acute damage to aquatic life in receiving waters as well as in
      regulating toxic waste discharges. The 96 h LC50 tests can be used to obtain
      toxicity data as rapidly and inexpensively as possible. In the present study,
      results showed a significant decrease in total glycogen, total lipids and total
      protein of liver, muscles and gills after 24 and 96 h of exposure to 96 h LC50 of
      hexavalent chromium (43.7 mg L(-1)). Cytotoxicity of metals is important because
      some metals are potential mutagens able to induce tumors in humans and
      experimental animals, the treatment of(Cr VI) at 43.7 mg L(-1) was for 24 and 96
      h, respectively. DNA was extracted after treatment from brain and liver of the
      tested fish. Our results showed appearance of polymorphic bands at the long
      treatment interval (96 h) ofhexavalent chromium. However, these bands were not
      appeared when the fish were exposed to the (Cr VI) for the short treatment
      interval (24 h). Histopathological changes were seen in liver, muscle and gills
      sections of chromium-exposed fishes. The obtained results were discussed in the
      study research.

PMID- 19090269
TI  - A review on the collection, preservation and systematic techniques in
      Phlebotominae.
AB  - The aim of present study is to discuss the taxonomic and biological history and
      significance of Phlebotominae sand flies giving emphasis on their collection,
      preservation and identification of new species as well as differentiation of male
      and female. Several species of Phlebotominae sand flies are known throughout the
      world including India. These Phlebotominae sand flies are economically important
      natural enemies of human beings and cause Kala-azar and visceral leishmaniasis.
      This causes a lot of deaths. Taxonomy plays an important role in identifying
      these tiny insects accurately. The accurate identification is important to apply
      relevant control measures. A wrong identification may lead to misleading results
      and may upset the entire control strategy. From the start of sand fly research
      various methods for collection and identification were used. In the early
      twentieth century, the use of internal structures particularly, cibarium, pharynx
      and spermathecae was introduced as taxonomic characters. The identification of
      female sand flies was always found to be difficult and hence scanty work on
      females are available. Recently female external as well as internal genital
      structures are used for their identification. Another important character is the
      genital filament/spermathecal duct ratio which could be a good point for
      taxonomic differentiation of male and female Phlebotominae sand flies. The
      detailed study of some biologically important structures of sand flies e.g.,
      mouthparts and reproductive organs both internal as well as external have led to
      the introduction of few new taxonomic characters.

PMID- 19090270
TI  - Standardization of mass production in three isolates of nucleopolyhedrovirus of
      Helicoverpa armigera (Hubner).
AB  - The effect of four major parameters, viz., larval age and weight, inoculation
      dose, incubation temperature and time of harvesting the larvae, on the production
      of three isolates of nucleopolyhedrovirus of Helicoverpa armigera (HaNPV), viz.,
      Ooty (OTY), Coimbatore (CMB) and Negamum (NGM) were evaluated. Early 5th instar
      larvae recorded the maximum yield of virus per larva when inoculated with a dose
      of 5x10(5) POB larva(-1) and incubated at a temperature of 25 degrees C. Also,
      highest POB yield was recorded when virosed larvae were harvested as cadavers.
      However, among the isolates tested in this study, CMB isolate collected from
      Tamil Nadu, India, showed the highest yield per larva in all of the conditions.

PMID- 19090271
TI  - Integrating GIS and fuzzy logic for urban solid waste management (a case study of
      Sanandaj city, Iran).
AB  - The city of Sanandaj with population of 340000 in 2003 produces 714 tons of solid
      waste per day. Waste dumping is the main method of solid waste disposal during
      the thirty past years. The conditions show that the present site is quite
      unsuitable because many principles and criteria for site selection are not
      considered. So in the near future, the severe environmental impacts will threats
      the health of Sanandaj's inhabitants. The research attempts to integrate fuzzy
      logic and GIS with the help of Remote Sensing in selecting the most suitable area
      for the waste disposal. In this study we georeferenced many data which ranges
      from physical to socio-economic to monitor the impacts of all different factors.
      Some of these factors are; distance from the legal limits of the city, distance
      from main road, airport, main urban utilities, other human settlements, surface
      water resources, wind direction, population density, gradient, fault line,
      vegetation cover and geology. The data and information has been integrated and
      then by using satellite images, three areas in the 20 km of north east of
      Sanandaj city were identified for the solid waste disposal.

PMID- 19090272
TI  - Phosphorus and nitrate removal by selected wastewater protozoa isolates.
AB  - In the present study, the efficiency often selected wastewater protozoa in the
      removal of phosphorus and nitrogen and their effects on other physico-chemical
      parameters was investigated. Protozoa were isolated from the aerobic zone of
      Daasport wastewater treatment plant, in Pretoria, South Africa, using the
      modified Chalkey's medium. The isolates were screened for nutrient removal
      ability in shake flasks, at laboratory temperatures for 96 h. During each
      sampling, aliquot samples were collected for the analysis of phosphorus, nitrate
      nitrogen, Chemical Oxygen Demand (COD), Dissolved Oxygen (DO), pH, of the mixed
      liquor including the growth rate of the isolates using standard methods. The
      results indicated a steady increase in growth rate of the isolates and all the
      isolates used in this study showed some measure of phosphorus and nitrate removal
      ability. In the presence of the test protozoa isolates, an increase in COD and a
      decrease in DO were noted in the mixed liquor inoculated with the organisms,
      while the pH only increases slightly. This study revealed a significant
      correlation between growth rate and nutrient removal (R = -0.806, p < 0.001 for
      phosphorus; R = -0.799, p < 0.01 for nitrate). The present study has been able to
      show that certain protozoa isolates have the ability to biologically remove
      phosphorus and nitrate from effluent. Consequently, it would be necessary to
      identify what strains of protozoa are capable of excess phosphorus and nitrogen
      uptake for the treatment of wastewater.

PMID- 19090273
TI  - Detection of Legionella pneumophila by PCR-ELISA method in industrial cooling
      tower water.
AB  - Water supply and Cooling Tower Water (CTW) are among the most common sources of
      Legionella pneumophila (LP) contamination. A nonradio active method is described
      to detect LP in industrial CTW samples. DNA was purified and amplified by nested 
      PCR with amplimers specific for the 16s rRNA gene of LP. The 5' end biotinylated
      oligomer probe was immobilized on sterptavidin B coated microtiter plates. The
      nested-PCR product was labeled with digoxigenin and then hybridized with 5'
      biotinylated probes. The amplification products were detected by using proxidase
      labled anti dioxygenin antibody in a colorimetric reaction. The assay detected LP
      present in 1 L of 5 CTW samples examined. All of the samples were Legionella
      positive in both culture and PCR-ELISA methods. The PCR-ELISA assay appears to
      exhibit high specificity and is a more rapid technique in comparison with
      bacterial culture method. Thus could prove suitable for use in the routine
      examination of industrial CTW contamination.

PMID- 19090274
TI  - Effects of water stress on respiration, photosynthetic pigments and water content
      in two maize cultivars.
AB  - Water stress is one of the most important environmental factors that reduce
      growth, development and production of plants. Stress was applied with
      polyethyleneglycol (PEG) 6000 and water potentials were: zero (control), -0.15
      (PEG 10%), -0.49 (PEG 20%), -1.03 (PEG 30%) and -1.76 (PEG 40%) MPa. The roots
      and leaves respiration of two maize (Zea mays L.) cultivars -704 and 301- were
      determined in various concentrations of PEG 6000. Oxygen uptake declined in
      leaves and roots with increasing PEG concentrations. Decrease of oxygen uptake in
      roots and leaves of 704 variety were higher than 301 variety. Chlorophyll a, b
      and total chlorophyll content were significantly decreased (p < 0.05), but
      carotenoids content increased (p < 0.05) under water stress. Decrease of
      chlorophyll content in 704 var. was higher than 301 var., but carotenoids content
      in 301 var. was higher than 704 var. Relative Water Content (RWC) was used to
      indicate the degree of stress. RWC decreased with increasing PEG concentrations.
      Lowering of RWC reduced growth and increased shoot/root ratio. Decrease of water
      content in 704 plants was higher than 301 plants. Shoot/root ratio in 704 var.
      was higher than 301 var.

PMID- 19090275
TI  - The food habit of Epinephelus coioides (Hamilton, 1822) in Khuzestan coastal
      waters (Persian Gulf).
AB  - During January 2000 to March 2001, a large number of Epinephelus coioides species
      was captured in main fishing areas of Khuzestan province namely, Busafe-Liphe and
      Bahrakan, North of Persian Gulf. The stomach contents of 394 individuals were
      analysed, in which 226 individuals had contained (trace-full) stomachs while 168
      individuals had empty stomachs. The percentages of CV in males were more than in
      females. Seventy three percent of stomachs contained fish 11% crab; 8.8% shrimp;
      3.9% squid; 1.7% gastropod and 0.4% bivalves. The intensity of feeding in monthly
      sampling periods and length groups did not show a clear trend. The results of Fp
      index showed 73% for fish; crab 11%; shrimp 8.8%; squid 3.9%; gastropod 1.7 and
      0.4% for bivalvia. Similar pattern of feeding was observed using CN index. The
      main food items for E. coioides were fish followed by crabs and accidental food
      items were shrimp, squid, gastropods and bivalvia.

PMID- 19090276
TI  - Spasmolytic effect of Petroselinum crispum (Parsley) on rat's ileum at different
      calcium chloride concentrations.
AB  - Traditional herbal medicines such as Petroselinum crispum (Parsley) have been
      used for treatment of intestinal disorders in Iran. To date no pharmacological
      evidence for their effectiveness has been reported. The aim of this study was to
      examine the relaxant effect of hydroalcoholic extract of Petroselinum crispum on
      isolated adult male Wistar rat's ileum contraction by KCl 60 (mM). The extract
      was prepared from parsley seed with 80% ethanol. A portion of ileum was removed
      and placed in an organ bath containing Tyrode solution (37 degrees C, pH = 7.4)
      bubbled with air. From a resting tension of 1 g, isotonic Transducer and Harvard
      Universal Oscillograph were used for recording contraction of ileum after
      administration of 60 mM KCl. Various concentration of extract were added to the
      bath. This experiment showed that, the extract in a dose-dependent manner
      decreased the induced-KCl ileums contraction (n = 7, p < 0.001). Also adding
      extract before influence of KCl, cause reduced effect of KCl (n = 7, p < 0.001).
      In addition, the Tyrode solution without CaCl2 and high concentration of K+,
      various concentration of extract significantly (n = 7, p < 0.001) decreased the
      CaCl2-induced contraction. Therefore, it seems that the relaxation effect of
      extract alcoholic parsley seed on the contraction of ileum is performed by
      blocking of voltage-gated calcium channels.

PMID- 19090277
TI  - Influence of osmo and hydropriming on seed germination and seedling growth in
      wheat (Triticum aestivum L.) cultivars under different moisture and temperature
      conditions.
AB  - Insufficient seedling stand establishment is one of the major obstacles to
      achievement of winter wheat (Triticum aestivum) potential yield. In the present
      study, seeds of eleven wheat cultivars differing in drought resistance were
      subjected to hydropriming with distilled water and osmopriming with PEG 6000 for
      12 h. Speed of emergence, vigor index and seedling dry weight were studied under
      two temperature conditions at 11 and 18 degrees C in plant growth incubators.
      Water stress started 15 Days After Sowing (DAS). As compared with osmopriming,
      hydropriming clearly improved speed of emergence, vigor index and seedling dry
      weight. The results were more evident at 11 degrees C indicating that
      hydropriming is more efficient for cold rather than temperate area. At both
      temperatures, PEG treatment severely diminished above mentioned traits. At 11
      degrees C, drought resistant cultivars i.e., Sardari, Agosta-Sefid, Azar 2 and
      Sabalan had higher seedlings dry weight as compared with susceptible ones.
      Therefore, it is proposed that measurement of seedling dry weight may be a proper
      approach for early screening of wheat drought resistant genotypes.

PMID- 19090278
TI  - Evaluation of a new tillage tool; considering soil physical property, energy
      requirement and potato yield.
AB  - Two series of field experiments were conducted for this comparison study, one in
      the UK and the second in Iran. First, the effects of each implement on the soil
      structure were investigated. Then these implements were used in the preparation
      of a potato seedbed for a final evaluation. Soil physical changes were measured
      including soil aggregate size analysis, cone penetrometer resistance, bulk
      density, surface relief and soil moisture content before and after cultivation.
      The field experiments concluded that an overall improvement of about 40% in
      output (ha h(-1)) could be obtained when using the new plow (combination of disk
      and chisel) compared with a conventional plow. The aggregate analysis of the
      cultivated layer revealed that the performance of the two machines was largely
      similar and no significant differences were seen in potato production rates
      during two years of field experiments, indicating no disadvantage from using an
      alternative to the moldboard plow.

PMID- 19090279
TI  - Thermal effect on the biology and life tables of Bemisia tabaci Gennadius
      (Homoptera: Aleyrodidae).
AB  - The life history and life table of Bemisia tabaci Gennadius on cucumber was
      studied under laboratory conditions at 20, 25 and 30 degrees C. The overall
      developmental time varied from 34.8 days at 20 degrees C to 14.1 days at 30
      degrees C. Immature mortality decreased from 45.8 to 17.3% with increasing
      temperature. The threshold temperatures of egg, 1st, 2nd, 3rd and 4th nymphal
      stage and a generation were 14.72, 14.36, 10.18, 11.40, 14.36 and 13.07 degrees C
      whereas the degree-day requirement at each stage was 64.44, 42.39, 49.19, 33.19,
      35.46 and 229.52 DD, respectively. Female longevity ranged from 16.8-34.1 days.
      Mean total fecundity ranged from 150-263 eggs/female. Mean daily fecundity ranged
      from 4.2-12.7 eggs/female, increasing with increasing temperature. Values for
      r(m) varied from 0.066 to 0.191 being least at 20 degrees C and greatest at 30
      degrees C. Generation times decreased from 43 to 19 days with increasing
      temperature. The results indicate that B. tabaci is well adapted to high
      temperatures and may extend its distribution if mean world temperatures increase
      as a result of global warming.

PMID- 19090280
TI  - Ecological studies on Al-Khadoud Spring, Al-Hassa, Saudi Arabia.
AB  - Al-Khadoud spring is one of the most important water resources in Al-Hassa
      Governorate, Saudi Arabia. However, much of its biotic information is still
      unknown. This study presented preliminary ecological information of this aquatic
      body. Regarding to macrophytes, a total of eight species were observed along the
      study sites. These species include two submerged aquatic plants (Potamogeton
      pectinatus L. and Ceratophyllum demersum L.). The common distributed species are
      Phragmites australis (Cav.) Trimex Steud and Cyperus rotundus (L.). On the other
      hand, a total of 20 algal genera were recorded with 7 genera of Chlorophyceae, 8
      of Bacillariophyceae, 4 of Cyanophyceae and one of Euglenophyceae. The common
      phytoplankton occurred in all three investigated sites were Chlorella vulgaris,
      Mougeotia sp., Oscillatoria sp. and Actinastrum sp. Regarding to the biotic
      fauna, different forms of unicellular zooplankton such as Paramecium and Amoeba
      were recorded. Invertebrates such as freshwater insects and some freshwater
      snails were documented in the study sites including Melanodies tuberculata,
      Melanopsis praemorsa and Lymnaea auricularia. As regard to vertebrates, one
      species of fish, Aphanius dispar, dominate the spring basin and its extended
      channels.

PMID- 19090281
TI  - Effect of sowing distances on edible pod yields and yield components of three
      vegetable cowpea cultivars (Vigna unguiculata L. Walp.) Sesquipedalis subspecies,
      grown in Northeast Thailand.
AB  - This experiment was conducted at the Experimental Farm, Mahasarakham University,
      Mahasarakham 44000, Northeast Thailand in the 2006 (August to October) to
      investigate effect of sowing distances on edible pod yields and yield components
      of three vegetable cowpea cultivars (Vigna unguiculata L. Walp.) Sesquipedalis
      subspecies. The experiment was laid in a split plot arranged in a Randomize
      Complete Block Design with four replications. Five sowing distances were used as
      main plots (50x10, 50x20, 50x30, 50x40 and 50x50 cm between rows and within rows,
      respectively) and three cowpea cultivars were used as subplots (MSU 1, KKU 40 and
      SNU 1). The results showed that there were no statistical differences due to
      cultivars on total dry weight ha(-1), number of branches plant(-1), marketable
      pods ha(-1), 100-seed weight and total fresh weight of pods ha(-1) where in most
      cases genetic potential of the three cultivars were similar. Number of off
      standard pods was significantly highest with KKU 40 (6.13 pods plant(-1)), whilst
      MSU 1 and SNU 1 cultivars gave smaller values but both were similar (4.80 and
      4.53 pods plant(-1), respectively). The closest sowing distances (T1) gave
      significantly higher total dry weight ha(-1) and number of off standard pods
      plant(-1) than other treatments (T2-T5). An increase in sowing distances
      significantly increased number of branches plant(-1) up to T2 but T2 was similar
      to other higher sowing distances (T3-T5). Total marketable pods (12,196.50 kg ha(
      1)) and total fresh weight of edible pods (12,588.88 kg ha(-1)) were
      significantly highest with T3 where T3 was the most suitable sowing distances for
      either of the three cowpea cultivars (50x30 cm between rows and within rows,
      respectively).

PMID- 19090282
TI  - Restriction fragment length and single strand conformational polymorphisms in
      chicken mitochondrial phosphoenol-pyruate carboxykinase gene and its association
      with egg production.
AB  - This study analysed mitochondrial phosphoenol-pyruate carboxykinase (PEPCK-M)
      gene as a candidate QTL for egg production traits in chickens. Single Strand
      Conformational Polymorphism (SSCP) of a 300 bp DNA fragment, from exon 9 of
      samples from an egg laying North American commercial White Leghorn stock,
      revealed a total of 6 different single strand conformers, indicative of 3
      alleles. Subsequent DNA sequencing found a total of 4 base changes in this
      fragment between these alleles (called A1, A2 and A3) when compared to the
      reference sequence published online. The A1 allele had one transition mutation of
      T to C at position 1700. The A2 allele had accumulated three transition
      mutations: T to C at position 1578, A to G at position 1647 and T to C at
      position 1650. Transition mutation of T to C at position 1578 of the A2 allele
      results in the loss of an AccI site, hence, producing a de novo RFLP. Analysis of
      358 female individuals from this strain showed that the population is highly
      polymorphic at this site. The effect of PEPCK-M genotypes at this site, namely
      AccI -/-, AccI +/- and AccI +/+, was tested on three traits, age at first egg,
      egg production rate and egg number. Least square analysis showed that exon 9 RFLP
      significantly affects age at first egg (p < 0.05). Egg production rate and egg
      number traits were not affected by different genotypes at this position. The data
      also indicates an over-dominance effect for the associated trait.

PMID- 19090283
TI  - Sodium and proline accumulation as osmoregulators in tolerance of sugar beet
      genotypes to salinity.
AB  - Twenty eight sugar beet genotypes were analysed for their tolerance at 3 NaCl
      levels (0, 3000 and 6000 mg NaCl kg(-1) soil) and Na+, K+, Na+/K+ and free
      proline were measured from the leaf samples. Results showed that increasing
      salinity level caused an increase in Na+, Na+/K+ and proline, but a decrease in
      K+ content of leaf samples (p < or = 0.01). As compared to non-tolerant
      genotypes, tolerant ones accumulated more Na+ and Na+/K+ and proline and less K+.
      It seems that Na+ and proline accumulation in shoots are effective mechanisms for
      osmotic pressure adjustment and plant tolerance to salinity, a mechanism commonly
      seen in sugar beet ancestors.

PMID- 19090284
TI  - Macrofungi of Tavas (Denizli) district in Turkey.
AB  - Macrofungi samples have been collected during the field trips carried out in
      Tavas (Denizli) between in 1999-2001. As a result of field and Laboratory studies
      totally 45 taxa belong to 19 families were identified. Nine of these belong to
      Ascomycetes and 36 to Basidiomycetes. Seventeen species are edible and four taxa
      are poisonous.

PMID- 19090285
TI  - Physiological effects of copper on some biochemical parameters in Zea mays L.
      seedlings.
AB  - Growth parameters and biochemical changes were studied in roots and leaves of 15
      day old maize grown in a nutrient solution containing various copper
      concentrations (0, 25, 50, 75 and 100 microM). An accumulation of H2O2 was
      observed in roots and shoots. The leaf chlorophyll a, b and carotenoid contents
      decreased with increasing Cu concentration. The results demonstrated adverse
      effects of Cu on N metabolism and plant growth. Cu exposure elevated Cu
      concentration and decreased Nitrate Reductase (NR) activity in the roots and
      shoots. However, Cu exposure increased total free amino acid content in the
      leaves.

PMID- 19090286
TI  - Evaluation of apoptosis induction using PARP cleavage on gastric adenocarcinoma
      and fibroblast cell lines by different strains of Helicobacter pylori.
AB  - Helicobacter pylori is one of the most common pathogens affecting humans and is
      the major environmental factor in the development of gastric cancer increasing
      from 4 to 6 folds the risk of its development. Variations in cancer risk among H.
      pylori infected individuals may correlate to difference in H. pylori strains,
      variable host characteristics and specific interactions between host and
      microbial determinants. To determine the effect of different strains of H. pylori
      on cellular apoptosis this study was designed an in vitro model using AGS and HEF
      cell lines. After specified time intervals total cell proteins was extracted and
      subjected to SDS-PAGE and immunoblotting using anti poly ADP-ribose polymerase
      (PARP) antibody. Decrease in densitometric value of PARP was indicative of higher
      level of apoptosis. The ability of apoptosis induction in AGS and HEF cell lines
      by wild type (cagA+/vacA+), cagA-/vacA+, vacA-/cagA+ and double negative (cagA
      /vacA-) strains were significantly different. The assessed apoptosis in AGS cell
      line co-cultured with wild type strain was 3.22 +/- 0.2 in 24 h, 2.8 +/- 0.1 in
      48 and 2.1 +/- 0.09 in 72 h of incubation time. Similar assessment with cagA
      /vacA+ strains in AGS cells was 4.17 +/- 1.49 in 24 h, 3.32 +/- 0.45 in 48 h and
      2.32 +/- 0.61 in 72 h incubation. A variation in apoptotic potential between the
      H. pylori strains on two cells (AGS and HEF) was observed. Based on present
      results, it is concluded that H. pylori strains as well as target cell types are
      important in pathogenesis and induction of apoptosis during a specified time
      interval.

PMID- 19090287
TI  - Detection of aflatoxin M1 in raw and commercial pasteurized milk in Urmia, Iran.
AB  - During the years 2005 and 2006, samples of raw and of pasteurized milk (72
      samples each) were collected randomly from various parts of Urmia city in Iran
      for the detection of aflatoxin M1. Aflatoxin M1 levels were assessed by Enzyme
      Linked Immuno Sorbent Assay (ELISA). There was a high incidence of AFM1 (100%),
      in both raw and pasteurized milk samples. The AFM1 levels in 6.25% of samples
      were higher than the maximum tolerance limit accepted by European Union (50 ng L(
      1)), while the observed mean ofAFM1 was lower than those proposed for European
      diets. Maximum level ofAFM1 in raw and pasteurized samples were 91.8 and 28.5 ng
      L(-1), while minimum levels were 4.3 and 5.1 ng L(-1), respectively. The levels
      ofAFM1 in total samples indicated that feeds for cows in this region were
      contaminated with AFB1 in such a level that appears to be a serious public health
      problem at the moment. Therefore, there is a need to limit exposure to aflatoxins
      by imposing regulatory limits.

PMID- 19090288
TI  - Proteomic analysis in human fibroblasts by continuous exposure to extremely low
      frequency electromagnetic fields.
AB  - Most people are Exposed to Extremely Low-Frequency Electromagnetic Fields (ELF
      EMF). A number of studies have indicated association between exposure to
      extremely low frequency electromagnetic fields and a variety of cancers. Recently
      some therapeutic techniques such as repetitive Transcranial Magnetic Stimulation
      (rTMS) have been used to study localization of brain function, connectively of
      brain regions and pathophysiology of neuropsychiatric disorders (rTMS utilize low
      frequency-electromagnetic field). Here, the effect of continuous ELF
      electromagnetic fields (3 Hz, sinusoidal, 3 h and 4 mT) on the protein expression
      of human fibroblast cells is investigated via proteomics. The comparison of the 2
      DE separated proteins from the exposed and sham (control) cells showed that some
      protein expressions are affected by radiation. The two proteins that their
      expression are reduced about 50% are determined as alpha 1 antitrypsin (A1AT) and
      Transthyretin (TTR). As it is reported that the amounts of these proteins reduced
      in the pathological conditions it can be concluded that application of ELF-EMF in
      therapeutic aspects may be to accompanying with their side effects.

PMID- 19090289
TI  - Plantlet regeneration potential from seedling explants of vitegnus (Vitex agnus
      castus).
AB  - In this research a simple and repeatable method for regeneration of a important
      medicinal plant (Vitex agnus castus) described. Different seedling explants such
      as hypocotyl, cotyledon, root and apical meristem were cultured in MS basal media
      with different kinds and concentrations of PGRs. Root and apical meristem
      explants were the only explants that have regeneration whole plantlets potential.
      It was interesting that regeneration whole plantlets from root and apical
      meristem explants have different developmental pathways. Whole plantlets from
      apical meristem explants regenerated by passing phase callusing whereas
      regeneration whole plantlets from root was direct and without phase callusing.
      This subject implies that we can have many manipulation possibilities in order to
      different objects of tissue culture by selecting different explants in vitegnus.

PMID- 19090290
TI  - In vitro plant regeneration from direct and indirect organogenesis of Memordica
      charantia.
AB  - The study was conducted to analyze the effect of plant growth regulators on
      callogenesis and direct and indirect organogenesis of Memordica charantia. Callus
      cultures were induced from leaf, stem and cotyledonary explants of Momordica
      charantia, at different auxin and cytokinin concentrations either in single or in
      combination in MS medium. The best callogenic response was observed from all
      three explants (leaf, stem and cotyledon) on MS medium supplemented with 1.0 and
      1.5 mg L(-1) BAP with 1.5 mg L(-1) NAA and 1.0 mg L(-1) 2,4-D, respectively. The
      callus produced was hard, green and compact. These totipotent cells were failed
      to give rise shooting response when transferred to same or different growth
      regulator containing medium as second subculture. Indirect organogenesis response
      was very low or absent due to hardening of callus and habitutation. Best shooting
      was observed at 1.0 mg L(-1) BAP + 0.1 TDZ and 1.5 mg L(-1) BAP + 0.2 mg L(-1)
      NAA from shoot tip and cotyledonary node explants. While root formation was
      achieved when generated shoots were transferred to MS medium both full and half
      strength supplemented with different auxin concentrations.

PMID- 19090291
TI  - Prevalence of Porphyromonas gingivalis and Bacteroides forsythus in chronic
      periodontitis by multiplex PCR.
AB  - The present research decided to study prevalence of Porphyromonas gingivalis and
      Bacteroides forsythus in chronic periodontitis patient by use of Multiplex PCR.
      The subgingival plaque samples from 61 patients suffering from chronic
      periodontitis with probing depth PD > or = 6 and 40 healthy controls were
      collected by sterile curette. In this study we used two species-specific Forward
      primers in combination with a single Reverse primer. These primers target
      variable and conserved region of 16S rRNA gene, respectively. The study included
      61 patients (34 women, 27 men; 24-69 years of age; mean 43) and 40 periodontally
      healthy controls (22 Women, 18 men, 21-69 years in age; mean 41.35%).
      Porphyromonas gingivalis was detected in 51 samples (83.61%) and 16 samples (40%)
      of chronic periodontitis patients and healthy subjects, respectively and
      Bacteroides forsythus was detected in 32 samples (52.50%) of chronic
      periodontitis patients and was not detected in any sample from healthy persons.
      We set up Multiplex PCR in order to detect P. gingivalis and B. forsythus
      simultaneously. The present data suggest that P. gingivalis is a more important
      cofactor in etiology of chronic periodontitis. Further studies are needed to
      determine spectrum of pathogenicity of the disease and effective management of
      diagnosis and treatment in order to decrease the risk of periodontic complicates
      such as systemic infection.

PMID- 19090292
TI  - The effects of weed-crop competition on nutrient uptake as affected by crop
      rotation and fertilizers.
AB  - A field study at the Agricultural University of Timiriazev, Moscow, was conducted
      to determine the effect of crop rotation and Long-term fertilizer application on
      differences in the competitive ability of spring barley and weeds to nutrient
      uptake in 2004 and 2005. Spring barley was cultivated in continuous and in crop
      rotation with winter rye, potato, clover, flax and fallow, with and without NPK
      application since 1912. Spring barley, especially in no fertilizer plots grown in
      crop rotation has greater dry mass than spring barley grown in continuous. While
      dry weed mass markedly decreased in crop rotation. Decrease dry weeds mass was
      greater when NPK had applied. The statistical analyses show that when spring
      barley grew in competition with weeds in the no fertilizer plots, crop rotation
      significantly increased nutrient content in spring barley, but when fertilizer
      applied the content of N, P2O5 and K2O in barley did not change. Lowest weeds
      nutrient content observed where soil fertility was increased by crop rotation and
      NPK application. Crop rotation significantly increased total nutrient uptake of
      soils by spring barley, but decreased total nutrient uptake by weeds.

PMID- 19090294
TI  - Some neuropharamacological effects of the crude extract of Conus parvatus in
      mice.
AB  - The present study was aimed to characterize the type of conotoxin present in
      Conus parvatus. (CP) belongs to family conidae, through neuro-pharmacological
      activities of the crude venom extract on some of the CNS animal experiment using
      mice as animal model. The effects of CP on CNS were studied, by using spontaneous
      motor activity, gross behavior, rota-rod performance, analgesic activity and
      potentiation of pentobarbitone sleeping time in mice. Preliminary evaluation of
      acute toxicity was also carried out; The LD50 value was found to be 425.20 mcg
      kg(-1) by i.p. route. The extract (200 mcg kg(-1) i.p.) was found to produce,
      reduction in spontaneous motor activity, potent analgesic activity, reduction in
      motor coordination and prolonged pentobarbitone-sleeping time. From the above all
      pharmacological activities, it may concluded that, the conotoxin present in CP is
      most likely to be a alpha-conotoxin and also it will be more suitable to continue
      the studies in the areas of analgesic and other CNS depressant therapeutic areas
      after isolation of the pure cono-peptide from CP.

PMID- 19090293
TI  - The efficacy of ethanolic extract of Lemon verbena on the skin infection due to
      Staphylococcus aureus in an animal model.
AB  - Daily increasing of Staphylococcus aureus resistance to various antibiotics in
      particular penicillin and Methecilin has led the scientist to look fore new
      medicines in this area. In an in vitro laboratory studies, it has been
      demonstrated that ethanolic extract of Lemon verbena can prevent the growth of
      Staphylococcus aureus. In this study the efficacy of ethanolic extract of Lemon
      verbena against Staphylococcus aureus skin infection were assessed in an in vivo,
      in animal model. 200lambda of Staphylococcus aureus suspension, were inoculated
      intradermally on the shoulder of 63 laboratory 20-30 g mice. the mice were
      divided in to 4 groups, 2 control groups: Negative (without treatment) and
      positive (treated with Mupirucin) and 2 test groups that treated for 7 days by
      ointment prepared from ethanolic extract of Lemon verbena (group 3), or injection
      of Lemon verbena solution (group 4). The status of wounds, the rate of recovery
      was studied and the presence of local pus after dissection of mice on day 8
      recorded and compared with each other. The wound appearance in the second day, on
      the injection site of S. aureus, in Group 1, 4, 3 and 2 were 84.2, 66.7, 46.2 and
      23.1%, respectively. In the final day, the lesion still was remained in 78.9,
      23.1, 92.3 and 77.7% in groups 1 -4, respectively. The necrotic and wide wounds
      were more observed in groups 1 and 3 vs two other groups. The results from this
      investigation indicate that the ointment prepared from ethanolic extract of Lemon
      verbena is a proper medication to prevent the skin infection by Staphylococcus
      aureus in early phase.

PMID- 19090295
TI  - Effect of different growing media on the growth and development of Dahlia (Dahlia
      pinnata) under the agro-climatic condition of Dera Ismail Khan.
AB  - An experiment was conducted to investigate the effect of different growing media
      on the growth and development of Dahlia (Dahlia pinnata). Seven different growing
      media including sand, silt, leaf mold, sand + silt, sand + leaf mold, silt + leaf
      mold and sand + silt + leaf mold, were used to check the growth and development
      of dahlia in pots. The over all best performance was recorded in media sand +
      silt + leaf mold for almost all the parameters; plant height (42.08 cm), stem
      thickness (1.93 cm), number of branches per plant (3.6), minimum days to
      flowering (91.66), number of flowers per plant (10.6), number of petals per
      flower (13), diameter of flower (8.8 cm) and vase life of flower (5 days). The
      media leaf mold alone also performed significantly well for all the parameters
      including the maximum 42.55 leaves per plant. Sand, when used alone as a growing
      medium showed the least response and provided unsatisfactory results for all the
      parameters.

PMID- 19090296
TI  - Antigen-specific lymphocyte proliferation assay and virus neutralization test for
      measurement of measles-specific immunity in 15-19 years old high school students
      in Tehran, Iran.
AB  - Limited information is available concerning the role of measles-specific cell
      mediated immunity as a correlate of long-term protection from measles infection.
      Although serological responses are determined in epidemiological studies and high
      antibody titer is a good indicator of protection, the role of Cell-Mediated
      Immunity (CMI) has to be defined more clearly. In this study, Lymphocyte
      Proliferation (LP) and Viral Neutralization Test (VNT) were used in order to
      measure measles-specific cellular and humoral immune responses of 100 high school
      students in Tehran. From total number of subjects studied, 33 were girls and 67
      were boys and all were in good health. Of these, 77 had protective neutralizing
      measles antibody titers and 23 did not have such titer. The results of LP showed
      that 89 subjects had protective cellular immune responses and 11 did not. A
      quantitative relationship between humoral and cellular immune responses was not
      observed. These findings suggest that measles-specific protective CMI is
      measurable for longer time in comparison to humoral immunity. These data suggest
      that LP responses may be better sustained than antibody titers in some children.

PMID- 19090297
TI  - Effect of marble industry effluent on seed germination, post germinative growth
      and productivity of Zea mays L.
AB  - A green house study was conducted at the University of Malakand, NWFP, Pakistan
      to evaluate the effect of marble industry effluent on soil pH, germination, post
      germinative growth and productivity of maize. The experiment was conducted in
      triplicate form for each treatment and tape water was used as control (T0).
      Effluents were diluted with tap water at concentration of 20% (T1), 40% (T2), 60%
      (T3), 80% (T4) and also used 100% (T5) concentration in 4 kg soil pot(-1) and
      plants were grown for 90 days. Results showed that there was a linear increase in
      pH of soil with increase in effluent concentration while germination, root length
      and stem girth was enhanced and found maximum at 40% concentration of effluent
      applied. The shoot length and root dry biomass was depressed as compared to
      control. It is concluded from the present study that marble industry effluent can
      be used as a fertilizer in low concentration especially for highly acidic soil
      but there is still need to carry out series of greenhouse and field trials to
      ascertain the fertilizer potentials of this effluent for maize crop.

PMID- 19090298
TI  - Life cycle and mating behavior of Zygotylenchus guevarai (Nematoda:
      Pratylenchidae) on excised Petroselinum crispum roots.
AB  - The life cycle and mating behavior of Zygotylenchus guevarai were observed in
      vitro on excised roots of Petroselinum crispum in gnotobiotic culture. Eggs
      hatched into juveniles whose appearance and structure were similar to those of
      the adults. Juveniles grew in size and each juvenile stage was terminated by a
      molt. Z. guevarai had four juvenile stages with the first molt occurred outside
      the egg shortly after hatching. After the final molt the juveniles differentiated
      into adult males and females. Mating was required for reproduction. After mating,
      fertilized females began to lay eggs. The life cycle from second stage juvenile
      to second stage juvenile was completed in 43 days.

PMID- 19090299
TI  - Evaluation of selective and nonselective media for isolation of Helicobacter
      pylori from gastric biopsy specimens.
AB  - The aim of the present study was to compare six media, three selective and three
      nonselective media, to determine the best combination of media for the primary
      isolation of Helicobacter pylori. Over a period of 8 months, mucosal antral
      biopsy specimens were obtained from 97 dyspeptic patients undergoing endoscopy.
      Biopsy samples were plated in parallel on all six media. Egg yolk emulsion agar
      (EYE), Skirrow's medium and modified Thayer-Martin medium were used as selective
      media; modified chocolate agar (MCHOC), Triptycase Soy Agar (TSA) and brain heart
      infusion agar were used as nonselective media. Overall, by using these six media,
      H. pylori were recovered from biopsy specimens from 48 of 97 patients, yielding
      an isolation rate of 49%. Comparison of all possible combinations of the six
      media showed that the highest rate of isolation of H. pylori was 100% (48 of 48)
      with EYE-MCHOC, followed by 97% (47 of 48) when EYE-SK was used. Conversely, it
      was found that none of the media used alone yielded a 100% rate of recovery (the
      maximum recovery rate was 92%, which was achieved with EYE). These results
      indicate that the association of EYE and MCHOC yielded the maximum recovery of H.
      pylori from gastric biopsy specimens. Therefore, the use of selective and
      nonselective media in parallel offers optimal recovery rates with only a slight
      increase in costs.

PMID- 19090300
TI  - Karyotype and C-banding patterns of mitotic chromosomes in Heteranthelium
      piliferum.
AB  - The C-banded karyotype of Heteranthelium piliferum species was studied in a
      natural population from northwest of Iran using aceto-iron-hematoxilin staining
      and C-banding technique. Chromosome measurements including long arm, short arm
      and chromosome lengths, arm ratio index, relative chromosome length,
      heterochromatin percent per chromosome and per chromosome set were made. It was
      revealed that the karyotype of this species is symmetric and consists of 7 pairs
      of metacentric chromosomes. Arm ratio index values ranged from 1.01 in chromosome
      G to 1.44 in chromosome D. One of the chromosomes had a satellite located on the
      end of its long arm (chromosome G). The Q genome of this species like A, B, D, S,
      M and M, genomes in diploid species of Aegilops-Trticum group, H genome in
      Hordeum, E genome in Agropyron and R genome in Secale has metacentric or sub
      metacentric chromosomes.

PMID- 19090301
TI  - Effect of different levels of feed added black seed (Nigella sativa L.) on the
      performance of broiler chicks.
AB  - The study was conducted to investigate the effect of different levels of feed
      added black seed (Nigella sativa L.) on the overall performance and immunity of
      broiler chicks at NWFP Agricultural University, Peshawar in May 2005. Four
      experimental rations designated as A, B, C and D having black seed at the rate of
      0, 20, 30 and 40 g kg(-1) feed were fed to 160 broiler chicks, randomly
      distributed into 16 replicates, so as to have 4 replicates per group and 10
      chicks per replicate. The experiment was lasted for 35 days. Average weight gain,
      feed consumption, feed efficiency, dressing percentage, weight of different body
      organs (breast, thigh, intestine), giblets (liver, gizzard), abdominal fat
      weight, antibody titer against ND, IB and IBD were used as criteria of response.
      Economics for each group was calculated at the end of experimental period. It was
      found that group D receiving 40 g kg(-1) of black seed in the feed had a
      significant (p < 0.05) effect on mean body weight gain, feed intake, feed
      conversion ratio, dressing percentage and weight of different body organs (breast
      and thigh). Non significant (p > 0.05) effect was observed in gizzard, intestine,
      weight of abdominal fat and feed cost. Antibody titer against ND and IBD were
      higher in group D, however high antibody titer against IB was recorded in group
      C. Return per unit of feed cost and gross return were significantly (p < 0.05)
      effected by group D.

PMID- 19090302
TI  - Pharmacokinetic of sulfisoxazole in aqueous humor after topical and
      subconjunctival application in dogs.
AB  - This study was undertaken to evaluate the ocular pharmacokinetic of
      sulfisoxazole. Male, 2-3 years old 10 mix breed dogs weighing 12-15 kg were used.
      A 2 mg dose/eye of sulfisoxazole was administrated to the animals by either
      subconjunctivally or by topically. Samples of aqueous humor were collected after
      0.083, 0.25, 0.5, 1, 2, 4, 6, 24 and 72 h and level of sulfisoxazole was
      determined. Pharmacokinetic parameters including absorption rate constant (k(a)),
      slope factor (beta), absorption half-life (t1/2a), half-life of elimination in
      aqueous humor (t1/2beta), maximal concentration in aqueous humor (C(max)), time
      to reach C(max) (t(max)), mean residence time in aqueous humor (MRT) and area
      under the concentration time curve from zero up to infinity (AUC(0-infinity))
      were calculated. Compared to topical application, value of k(a) in
      subconjunctival application increased while values of t1/2a and t(max) decreased
      and the value of t1/2beta prolonged (p < 0.05). There was no significant
      difference between groups regarding other parameters (p > 0.05). These results
      indicate that sulfisoxazole may not be potent enough to treat intraocular
      infections caused by bacteria when applied either subconjunctivally or topically
      at a dose of 2 mg/eye. Furthermore, subconjunctival application of sulfisoxazole
      could be more efficient for treatment of intraocular infections due to higher
      absorption of drug and longer remaining time in the eye compared to topical
      application.

PMID- 19090303
TI  - Separation of active and toxic portions in Sambucus ebulus.
AB  - Methanol extract of fruits, leaves and roots of Sambucus ebulus were investigated
      for antiinflammatory activity in rats (successively, after hexane and ethyl
      acetate extractions). Nearly all extracts produced statistically significant
      inhibition of edema induced by carrageenan at all doses when compared to the
      control groups. Anti-inflammatory effect was generally dose-dependent. The
      highest activity showed in fruits and leaves that at 600 mg kg(-1) i.p. inhibited
      86 and 71% inflammation respectively (76% for diclofenac at 100 mg kg(-1) i.p.).
      No extracts exhibit any toxicity up to 2 g kg(-1) body weights intraperitoneally
      in mice. Ethyl acetate extract were withdrawn because of severe nociceptive
      response in rats. This extract showed severe toxicity (in particular, severe
      liver abscess) in all mice at all tested doses (125-1500 mg kg(-1) i.p.).

PMID- 19090304
TI  - Isolation of stigmasterol and beta-sitosterol from methanolic extract of root
      bark of Calotropis gigantea (Linn).
AB  - Aim of this study is to identify and characterize the bioactive principles from
      the root bark of Calotropis gigantea. It has wide folk medicinal use. For
      isolation of the compounds, the dried root bark's powder of Calotropis gigantea
      were subjected to hot extraction and then the crude methanol (MeOH) extract was
      fractionated with petroleum ether, chloroform and ethyl acetate. Two compounds
      were isolated and purified from petroleum ether fraction of crude methanol
      extract and the structures were determined as stigmasterol and beta-sitosterol by
      analysis of physical, chemical and spectral characteristics (1D NMR and mass
      spectrometry).

PMID- 19090305
TI  - Chemical composition and antibacterial activity of Cochlospermum planchoni
      Hook.f. ex Planch essential oil from Burkina Faso.
AB  - The water distilled oil obtained from rhizomes of Cochlospermum planchonii
      Hook.f.ex Planch (Apocynaceae) from Burkina Faso was examined by GC and GC/MS.
      Cochlospermum planchonii oil presents a particular chemical composition with a
      high rate of oxygenated components with predominance of ketones and esters
      (86.4%). The essential oil was tested against twelve strains of bacteria using a
      broth microdilution method. The results suggest that Cochlospermum planchonii
      essential oil has significant bactericidal activity.

PMID- 19090306
TI  - Determination of carbon/nitrogen ratio and heavy metals in bulking agents used
      for sewage composting.
AB  - Improving the soil quality with organic matter and N, P and K contents are some
      of sewage sludge benefits. Adjusting carbonaceous materials such as plant wastes
      to dewatered sludge compost results in increasing the moisture content and
      improving C/N ratio. This study was conduced for three months in 2005, in
      Laboratory of Chemistry of Water and Wastewater in the School of Public Health of
      Isfahan University of Medical Science, to determine the C/N ratio and heavy
      metals concentration of bulking agents in sawdust, leaves, rice hulls and
      dewatered sewage sludge. Dewatered sludge was collected from Isfahan sewage
      treatment plant. Sawdust was collected from sawmills. Leaves were collected from
      municipality of Isfahan and rice hull from rice mills, then in samples determined
      C/N ratio and heavy metal according to standard methods. The results showed that
      concentrations of chromium and cadmium in the mixture of dewatered sewage sludge
      and bulking agents were lower them those of the standard level. Means of cobalt
      (115.44 mg kg(-1)), nickel (57.44 mg kg(-1)) and zinc (273.48 mg kg(-1))
      concentrations were maximum in dewatered sludge but mean concentration of cobalt
      (25.66 mg kg(-1)) in rice hull samples and mean zinc (8.99 mg kg(-1)) and nickel
      (5.106 mg kg(-1)) concentrations in sawdust samples were minimum. The optimal
      conditions sewage sludge composting, each kilogram of sludge needs 350 g of saw
      dust, 470 g of leaves and 388 g of rice hull. Amount of heavy metals present in
      the bulking agents is lower than the amount mentioned for the compost.

PMID- 19090307
TI  - Severe bradycardia after propofol induction.

PMID- 19090308
TI  - The medical-legal quandary of healthcare in capital punishment: an ethical
      dilemma for the anesthesia provider.
AB  - The case of Brase v Rees was presented before the US Supreme Court to consider
      the constitutionality of death by lethal injection as practiced in the state of
      Kentucky. The 3-drug combination of sodium thiopental, pancuronium bromide, and
      potassium chloride is a key aspect in question. Capital punishment conflicts with
      medical and nursing code of ethics preventing providers who are skilled at
      difficult intravenous (IV) access, assessment of appropriate sedation, and
      involvement without fear of disciplinary action. Therefore, untrained or
      undertrained personnel from the prison have been delegated these duties. Cases in
      which failure to establish or maintain IV access has led to executions lasting up
      to 90 minutes before the execution was complete. Participation by skilled medical
      personnel has been a debate between the medical and legal communities since the
      inception of lethal injection. Healthcare should reevaluate the ethical and moral
      principle of beneficence as the legal system attempts to evaluate the
      constitutionality of lethal injection. Can a nurse or doctor step out of the role
      of medical professional, use knowledge and skill to make death by lethal
      injection more humane, and not violate the ethical principle of "do no harm"?

PMID- 19090309
TI  - Cultural competency training in nurse anesthesia education.

PMID- 19090310
TI  - Comparison of 2 laryngeal tracheal anesthesia techniques in reducing emergence
      phenomena.
AB  - Endotracheal intubation (ETT) can cause emergence phenomena (EP) including
      coughing, sore throat, and dysphonia. Two methods used to prevent EP are the
      administration of local anesthetics directly onto airway structures using a
      specialized laryngotracheal instillation of topical anesthesia (LITA) tube
      (Sheridan Catheter Corporation, Argyle, New York) or the placement of a local
      anesthetic into the ETT cuff. The purpose of this study was to determine which
      method was better at preventing ERl In this prospective, randomized, comparative
      analysis, a sample of 160 ASA class I through III patients were randomly assigned
      to receive their EP prophylaxes either by placement of alkalinized lidocaine
      directly into the ETT cuff at intubation or by injection into a specialized port
      on the LITA tube approximately 30 minutes before extubation. Variables measured
      included the incidence and severity of sore throat, coughing, and dysphonia for
      the first 24 hours following surgery. The incidence of cough and sore throat was
      higher in the LITA group, achieving significance in the postanesthesia care unit
      and after discharge to home. No difference in any of the other variables was
      noted between groups. Our study demonstrated greater efficacy in decreasing the
      incidence and severity of EP by placing an alkalinized solution of lidocaine into
      the ETT cuff on intubation.

PMID- 19090311
TI  - Anesthesia in a child with pyruvate dehydrogenase deficiency: a case report.
AB  - We report a case in a pediatric patient with pyruvate dehydrogenase deficiency
      who presented for a left foot tendon transfer with an Achilles tendon lengthening
      secondary to left ankle equinus. The pathophysiology of pyruvate dehydrogenase
      deficiency is discussed as well as anesthetic management in patients with
      pyruvate dehydrogenase deficiency.

PMID- 19090312
TI  - Anesthesia for cesarean delivery in an achondroplastic dwarf: a case report.
AB  - There are more than 100 different types of dwarfism. Achondroplasia is the most
      common form of this rare condition. The incidence of achondroplasia in the United
      States is about 15 per 1 million births. Although inherited as an autosomal
      dominant condition, 80% of cases result from spontaneous mutation.
      Underdevelopment and premature ossification of bones result in characteristic
      craniofacial and spinal abnormalities. Limited neck extension, foramen magnum
      stenosis, a large tongue, large mandible, and atlanto-axial instability can lead
      to increased difficulty of airway management. Severe kyphosis, scoliosis, spinal
      stenosis, and unpredictable spread of local anesthetics in the epidural space and
      subarachnoid space lead to reluctance to apply regional anesthesia in this
      patient group. In addition, pregnancy in a person with achondroplasis poses more
      problems for anesthetic selection. These problems include potential hypoxia,
      severely decreased functional residual capacity, risk of gastric aspiration, and
      supine hypotension. In this case report, we describe the anesthetic management of
      an achondroplastic dwarf who underwent cesarean delivery.

PMID- 19090313
TI  - A successful partnership to help reduce health disparities: the Institute for
      Culturally Competent Care and the Kaiser Permanente School of
      Anesthesia/California State University Fullerton.
AB  - An innovative partnership with Kaiser Permanente's Institute for Culturally
      Competent Care (ICCC) enabled the Kaiser Permanente School of
      Anesthesia/California State University Fullerton (KPSA) to present a formal, 4
      module cultural competency certification program within the nurse anesthesia
      curriculum. The goals of developing the cultural competency curriculum were to
      increase students' awareness of cultural differences and to enhance students'
      communication skills with an increasingly diverse patient population. The
      cultural competency courses are integrated throughout the nurse anesthesia
      curriculum. During their clinical education, nurse anesthesia students travel to
      numerous urban and rural areas to serve diverse patient populations. The
      collaboration between the ICCC and KPSA represents a unique opportunity for the
      organization and for KPSA to have an impact on patient care. This article
      describes the genesis and evolution of the collaboration as well as the impact of
      this ongoing educational effort.

PMID- 19090314
TI  - Multidisciplinary management of peripartum cardiomyopathy during repeat cesarean
      delivery: a case report.
AB  - Peripartum cardiomyopathy is a potentially fatal form of heart failure associated
      with pregnancy. A 29-year-old African American woman, gravida 3, para 2, at 36
      weeks' gestation had a history of cardiomyopathy, morbid obesity (body mass index
      > 70 kg/m2), uncontrolled hypertension, obstructive sleep apnea, and required a
      repeat cesarean delivery. The patient was admitted to the hospital several times
      throughout her pregnancy for congestive heart failure, pulmonary edema, and
      headaches. Two years previously the patient received a diagnosis of peripartum
      cardiomyopathy 3 weeks after the delivery of her second child. This case report
      illustrates the recognition of peripartum cardiomyopathy and the risks early in
      pregnancy. It also describes the appropriate medical management, including
      transesophageal echocardiography and the need for collaboration of multiple
      medical specialists before and during delivery to provide the best possible
      outcome for both mother and infant.

PMID- 19090315
TI  - Implications of immune function to anesthesia care.
AB  - Multiple aspects of perianesthesia care and the perioperative environment can
      influence the functions of the immune system. This course reviews basic immune
      system functions and potential sources of immune system-altering perioperative
      stress. The effects of commonly used anesthesia drugs, opioids, and adjunct drugs
      on immune function are discussed. Patient populations at risk for increased
      morbidity due to perioperative immune depression are identified, along with
      patient-specific measures nurse anesthetists can take to reduce postoperative
      immune dysfunction.

PMID- 19090316
TI  - Gaps that wake you up.

PMID- 19090317
TI  - Subclinical REM sleep behavior disorder and its clinical and research
      implications.

PMID- 19090319
TI  - Night shift performance is improved by a compromise circadian phase position:
      study 3. Circadian phase after 7 night shifts with an intervening weekend off.
AB  - STUDY OBJECTIVE: To produce a compromise circadian phase position for permanent
      night shift work in which the sleepiest circadian time is delayed out of the
      night work period and into the first half of the day sleep period. This is
      predicted to improve night shift alertness and performance while permitting
      adequate late night sleep on days off. DESIGN: Between-subjects. SETTING: Home
      and laboratory. PARTICIPANTS: 24 healthy subjects. INTERVENTIONS: Subjects
      underwent 3 simulated night shifts, 2 days off, and 4 more night shifts.
      Experimental subjects received five, 15 minute bright light pulses from light
      boxes during night shifts, wore dark sunglasses when outside, slept in dark
      bedrooms at scheduled times after night shifts and on days off, and received
      outdoor afternoon light exposure (the "light brake"). Control subjects remained
      in normal room light during night shifts, wore lighter sunglasses, and had
      unrestricted sleep and outdoor light exposure. MEASUREMENTS AND RESULTS: The
      final dim light melatonin onset (DLMO) of the experimental group was
      approximately approximately 04:30, close to our target compromise phase position,
      and significantly later than the control group at approximately 00:30.
      Experimental subjects performed better than controls, and slept for nearly all of
      the allotted time in bed. By the last night shift, they performed almost as well
      during the night as during daytime baseline. Controls demonstrated pronounced
      performance impairments late in the night shifts, and exhibited large individual
      differences in sleep duration. CONCLUSIONS: Relatively inexpensive and feasible
      interventions can produce adaptation to night shift work while still allowing
      adequate nighttime sleep on days off.

PMID- 19090318
TI  - Morphine increases acetylcholine release in the trigeminal nuclear complex.
AB  - STUDY OBJECTIVES: The trigeminal nuclear complex (V) contains cholinergic neurons
      and includes the principal sensory trigeminal nucleus (PSTN) which receives
      sensory input from the face and jaw, and the trigeminal motor nucleus (MoV) which
      innervates the muscles of mastication. Pain associated with pathologies of V is
      often managed with opioids but no studies have characterized the effect of
      opioids on acetylcholine (ACh) release in PSTN and MoV. Opioids can increase or
      decrease ACh release in brainstem nuclei. Therefore, the present experiments
      tested the 2-tailed hypothesis that microdialysis delivery of opioids to the PSTN
      and MoV significantly alters ACh release. DESIGN: Using a within-subjects design
      and isoflurane-anesthetized Wistar rats (n=53), ACh release in PSTN during
      microdialysis with Ringer's solution (control) was compared to ACh release during
      dialysis delivery of the sodium channel blocker tetrodotoxin, muscarinic agonist
      bethanechol, opioid agonist morphine, mu opioid agonist DAMGO, antagonists for mu
      (naloxone) and kappa (nor-binaltorphimine; nor-BNI) opioid receptors, and GABAA
      antagonist bicuculline. MEASUREMENTS AND RESULTS: Tetrodotoxin decreased ACh,
      confirming action potential-dependent ACh release. Bethanechol and morphine
      caused a concentration-dependent increase in PSTN ACh release. The morphine
      induced increase in ACh release was blocked by nor-BNI but not by naloxone.
      Bicuculline delivered to the PSTN also increased ACh release. ACh release in the
      MoV was increased by morphine, and this increase was not blocked by naloxone or
      nor-BNI. CONCLUSIONS: These data comprise the first direct measures of ACh
      release in PSTN and MoV and suggest synaptic disinhibition as one possible
      mechanism by which morphine increases ACh release in the trigeminal nuclei.

PMID- 19090320
TI  - Modafinil increases arousal determined by P13 potential amplitude: an effect
      blocked by gap junction antagonists.
AB  - STUDY OBJECTIVES: We recorded the effects of administration of the stimulant
      modafinil on the amplitude of the sleep state-dependent auditory P13 evoked
      potential in freely moving rats, a measure of arousal thought to be generated by
      the cholinergic arm of the reticular activating system, specifically the
      pedunculopontine nucleus (PPN). DESIGN: Groups of rats were implanted for
      recording auditory evoked responses and the effects on P13 potential amplitude of
      intracranial injections into the PPN of neuroactive agents determined.
      MEASUREMENTS AND RESULTS: The effects of intracranial injections into the PPN of
      modafinil showed that P13 potential amplitude increased in a dose-dependent
      manner at doses of 100, 200, and 300 microM. The effect was blocked by
      pretreatment with either of the gap junction antagonists carbenoxolone (300
      microM) or mefloquine (25 microM), which by themselves slightly decreased P13
      potential amplitude. CONCLUSIONS: These results suggest that modafinil increases
      arousal levels as determined by the amplitude of the P13 potential, an effect
      blocked by gap junction antagonists, suggesting that one mechanism by which
      modafinil increases arousal may be by increasing electrical coupling.

PMID- 19090321
TI  - The prevalence of insomnia, its sociodemographic and clinical correlates, and
      treatment in rural and urban regions of Beijing, China: a general population
      based survey.
AB  - STUDY OBJECTIVES: To determine the prevalence of insomnia, its sociodemographic
      and clinical correlates, and treatment patterns in Chinese people. DESIGN: A
      total of 5,926 subjects were randomly selected in the urban and rural areas of
      Beijing and interviewed using standardized assessment tools. Basic
      sociodemographic and clinical data were also collected. SETTING: Urban and rural
      regions of Beijing municipality, China. Patients or Participants Adult residents
      older than 15 years. Interventions N/A. MEASUREMENTS AND RESULTS: The prevalence
      of at least one type of insomnia was 9.2%; the rates of difficulty initiating
      sleep (DIS), difficulty maintaining sleep (DMS), and early morning awakening
      (EMA) were 7.0%, 8.0%, and 4.9%, respectively. Increased age (age >44 and 24
      years in the urban and rural samples, respectively), female sex, married,
      divorced, separated, or widowed marital status; having a major medical condition;
      and suffering from a psychiatric disorder were risk factors for all types of
      insomnia in both the urban and rural samples. A low level of education (primary
      school or illiteracy) was significantly associated with a higher likelihood of
      all types of insomnia in the urban sample. Current smokers and current drinkers
      were less likely to report any type of insomnia in the rural sample. Unemployment
      was associated with DMS in the urban sample, while it was associated with DIS and
      DMS in the rural sample. Only 5.4% of the participants with any type of insomnia
      reported their symptoms to medical practitioners. In contrast, nearly one-third
      of the subjects with insomnia reported taking benzodiazepines as sleep-enhancing
      drugs. CONCLUSIONS: Nationwide epidemiologic surveys are needed to further
      explore the prevalence of insomnia in China. The low percentage of subjects
      treated for insomnia indicates a major public health problem that should be
      addressed. Strict controls on use of benzodiazepines are warranted.

PMID- 19090322
TI  - APD125, a selective serotonin 5-HT(2A) receptor inverse agonist, significantly
      improves sleep maintenance in primary insomnia.
AB  - INTRODUCTION: Insomnia is a condition affecting 10% to 15% of the adult
      population and is characterized by difficulty falling asleep, difficulty staying
      asleep, or nonrestorative sleep, accompanied by daytime impairment or distress.
      This study evaluates APD125, a selective inverse agonist of the 5-HT(2A)
      receptor, for treatment of chronic insomnia, with particular emphasis on sleep
      maintenance. In phase 1 studies, APD125 improved sleep maintenance and was well
      tolerated. METHODOLOGY: Adult subjects (n=173) with DSM-IV defined primary
      insomnia were randomized into a multicenter, double-blind, placebo-controlled, 3
      way crossover study to compare 2 doses of APD125 (10 mg and 40 mg) with placebo.
      Each treatment period was 7 days with a 7- to 9-day washout period between
      treatments. Polysomnographic recordings were performed at the initial 2 screening
      nights and at nights (N) 1/2 and N 6/7 of each treatment period. RESULTS: APD125
      was associated with significant improvements in key sleep maintenance parameters
      measured by PSG. Wake time after sleep onset decreased (SEM) by 52.5 (3.2) min
      (10 mg) and 53.5 (3.5) min (40 mg) from baseline to N 1/2 vs. 37.8 (3.4) min for
      placebo, (P < 0.0001 for both doses vs. placebo), and by 51.7 (3.4) min (P =
      0.01) and 48.0 (3.6) min (P = 0.2) at N 6/7 vs. 44.0 (3.8) min for placebo.
      Significant APD125 effects on wake time during sleep were also seen (P < 0.0001 N
      1/2, P < 0.001 N 6/7). The number of arousals and number of awakenings decreased
      significantly with APD125 treatment compared to placebo. Slow wave sleep showed a
      statistically significant dose-dependent increase. There was no significant
      decrease in latency to persistent sleep. No serious adverse events were reported,
      and no meaningful differences in adverse event profiles were observed between
      either dose of APD125 and placebo. APD125 was not associated with next-day
      psychomotor impairment as measured by Digit Span, Digit Symbol Copy, and Digit
      Symbol Coding Tests. CONCLUSIONS: APD125 produced statistically significant
      improvements in objective parameters of sleep maintenance and sleep consolidation
      and was well tolerated in adults with primary chronic insomnia.

PMID- 19090323
TI  - EEG spectral analysis in primary insomnia: NREM period effects and sex
      differences.
AB  - STUDY OBJECTIVES: To compare NREM EEG power in primary insomnia (PI) and good
      sleeper controls (GSC), examining both sex and NREM period effects; to examine
      relationships between EEG power, clinical characteristics, and self-reports of
      sleep. DESIGN: Overnight polysomnographic study. SETTING: Sleep laboratory.
      PARTICIPANTS: PI (n=48; 29 women) and GSC (n=25; 15 women). INTERVENTIONS: None.
      MEASUREMENTS: EEG power from 1-50 Hz was computed for artifact-free sleep epochs
      across four NREM periods. Repeated measures mixed effect models contrasted
      differences between groups, EEG frequency bands, and NREM periods. EEG power
      frequency curves were modeled using regressions with fixed knot splines. RESULTS:
      Mixed models showed no significant group (PI vs. GSC) differences; marginal sex
      differences (delta and theta bands); significant differences across NREM periods;
      and group*sex and group*NREM period interactions, particularly in beta and gamma
      bands. Modeled power-frequency curves showed no group difference in whole-night
      NREM, but PI had higher power than GSC from 18-40 Hz in the first NREM period.
      Among women, PI had higher 16 to 44-Hz power than GSC in the first 3 NREM
      periods, and higher 3 to 5-Hz power across all NREM periods. PI and GSC men
      showed no consistent differences in EEG power. High-frequency EEG power was not
      related to clinical or subjective sleep ratings in PI. CONCLUSIONS: Women with
      PI, but not men, showed increased high-frequency and low-frequency EEG activity
      during NREM sleep compared to GSC, particularly in early NREM periods. Sex and
      NREM period may moderate quantitative EEG differences between PI and GSC.

PMID- 19090324
TI  - The influence of in utero exposure to smoking on sleep patterns in preterm
      neonates.
AB  - BACKGROUND: In utero exposure to smoking is known to adversely affect brain
      regions involved in behavioral state organization and could therefore interact
      with the neurophysiological development of neonates. STUDY OBJECTIVES: The
      present study investigated the effects of prenatal smoking exposure on sleep
      patterns in the preterm neonate. DESIGN: Overnight sleep patterns were
      polysomnographically assessed at thermoneutrality. Sleep continuity and structure
      were scored for the respective frequencies, durations and percentages of active,
      quiet, and indeterminate sleep and wakefulness after sleep onset. The number and
      duration of body movements were also analyzed. SETTING: The neonatal intensive
      care unit at Amiens University Medical Center (France). PARTICIPANTS: Healthy
      preterm neonates (postconceptional age: 33.9 +/- 6.0 weeks) were enrolled
      according to whether their mothers had not smoked at all during pregnancy
      (control group, n=19), smoked less during pregnancy (low-smoking group, Slow,
      n=10), or smoked more (heavy-smoking group, Sheavy n=10) than 10 cigarettes per
      day throughout pregnancy. MEASUREMENTS AND RESULTS: Neonates born to heavy
      smoking mothers had a significantly lower mean birth weight than controls (-21%)
      and displayed disrupted sleep structure and continuity: they slept less overall
      (with a higher proportion of active sleep and a lower proportion of quiet sleep)
      and had more wakefulness after sleep onset. Compared with controls, neonates from
      both smoking groups displayed more body movements and, as a result, more
      disturbed sleep. CONCLUSIONS: High prenatal smoking exposure modifies sleep
      patterns in preterm neonates by disrupting sleep organization and increasing
      nocturnal body movements. These findings raise the question of the repercussions
      of these sleep disturbances (at what is a critical stage in brain development) on
      the child's physiological and neurobehavioral outcomes.

PMID- 19090325
TI  - QT interval prolongation in future SIDS victims: a polysomnographic study.
AB  - OBJECTIVE: Previous data have suggested that a prolonged QTc interval during the
      first days of life can be associated with some cases of sudden infant death
      syndrome (SIDS). Analysis of heart rate variability during sleep in future SIDS
      victims has shown findings compatible with an imbalance in autonomic tone. We
      hypothesized that some future SIDS infants could have longer QTc intervals during
      sleep, compared with healthy control infants, and that this difference would
      correlate with the autonomic imbalance already found in these infants. METHODS:
      QTc intervals and a heart rate autoregressive power spectral analysis were
      calculated during the same periods in the polysomnographic sleep recordings of 18
      infants who eventually died of SIDS and of 18 control infants. The control
      infants were matched for sex, gestational age, postnatal age, birth weight, and
      sleep position. The median postnatal age was 8 weeks. RESULTS: Compared with
      control infants, future SIDS victims were characterized by having longer QTc
      intervals during total sleep (P = 0.019), rapid eye movement sleep (P = 0.045)
      and non-rapid eye movement sleep (P = 0.029). When the night was divided into 3
      equal parts, this difference was always present but was most marked during the
      last part of the night. There was, respectively, a negative and a positive
      correlation between parasympathetic activity and sympathovagal balance and median
      and maximum QTc interval values. CONCLUSION: Compared with QTc intervals in
      matched control infants, QTc intervals were increased in future SIDS victims.
      Such a prolongation could be related to the autonomic dysfunction already
      reported in these patients.

PMID- 19090327
TI  - Respiratory cycle-related EEG changes during sleep reflect esophageal pressures.
AB  - STUDY OBJECTIVES: Respiratory cycle-related EEG changes (RCREC) have been
      demonstrated during sleep by digital analysis and hypothesized to represent
      subtle inspiratory microarousals that may help to explain daytime sleepiness in
      patients with sleep-disordered breathing. We therefore examined for the first
      time associations between RCREC and esophageal pressure swings (deltaPes) that
      reflect work of breathing. DESIGN: Retrospective analysis. SETTING: Academic
      sleep laboratory. PATIENTS: Forty adults referred for suspected sleep disordered
      breathing. INTERVENTIONS: Polysomnography with esophageal pressure monitoring and
      automatic computation of deltaPes using a novel algorithm. RESULTS: Computed
      deltaPes for nearly all respiratory cycles during sleep correlated well with
      visual scoring of selected respiratory cycle samples (Spearman rho = 0.86, P <
      0.0001). The RCREC within the sigma EEG range (12.5-15.5 Hz) rather than that
      within other frequency ranges most often showed significant within-subject
      inverse correlations with deltaPes. In contrast, in between-subject comparisons,
      beta (15.5-30.5 Hz) and to a lesser extent theta (4.5-7.5 Hz) RCREC, rather than
      sigma RCREC, showed significant inverse associations with mean APes. CONCLUSIONS:
      Variation within subjects of sigma RCREC with APes supports previous evidence
      that RCREC within this range may reflect microarousals exacerbated by increased
      work of breathing. Correlation of beta and theta, but not sigma RCREC with
      deltaPes in between-subject comparisons is more difficult to explain but suggests
      that ranges other than sigma also deserve further investigation for clinical
      utility.

PMID- 19090326
TI  - Blood pressure and heart rate during continuous experimental sleep fragmentation
      in healthy adults.
AB  - STUDY OBJECTIVES: This paper aims to determine whether experimental arousals from
      sleep delay the sleep related fall in cardiovascular activity in healthy adults.
      DESIGN: We report the results of 2 studies. The first experiment manipulated
      arousals from sleep in young adults. The second compared the effect of frequent
      arousals on young and middle-aged adults. The influence of arousals were assessed
      in 2 ways; (1) the fall in cardiovascular activity over sleep onset and the early
      sleep period, and (2) the underlying sleep levels during the sleep periods in
      between arousals. SETTING: Both experiments were conducted in the sleep
      laboratory of the Department of Psychology, The University of Melbourne,
      Australia. PARTICIPANTS: There were 5 male and 5 female healthy individuals in
      each experiment between the ages of 18-25 years (Experiment 1) and 38-55 years
      (Experiment 2). INTERVENTIONS: Participants in Experiment 1 were aroused by
      auditory stimuli every (i) 2 min, (ii) 1 min, and (iii) 30 sec of sleep for 90
      min after the first indication of sleep. In a control condition, participants
      slept undisturbed for one NREM sleep cycle. Experiment 2 compared the control
      with the 30-sec condition in the young adults and in an additional group of
      middle-aged adults. MEASUREMENTS AND RESULTS: The dependent variables were blood
      pressure (BP) and heart rate (HR). In Experiment 1, sleep fragmentation at higher
      frequencies retarded the fall in BP over sleep onset but did not affect the
      underlying sleep levels. Experiment 2 showed that there were no age differences
      on the effect of arousals on changes in BP and HR during sleep. CONCLUSIONS: This
      paper supports the hypothesis that repetitive arousals from sleep independently
      contribute to elevations in BP at night.

PMID- 19090329
TI  - Sympathetic withdrawal augments cerebral blood flow during acute hypercapnia in
      sleeping lambs.
AB  - STUDY OBJECTIVES: Cerebral sympathetic activity constricts cerebral vessels and
      limits increases in cerebral blood flow (CBF), particularly in conditions such as
      hypercapnia which powerfully dilate cerebral vessels. As hypercapnia is common in
      sleep, especially in sleep disordered breathing, we tested the hypothesis that
      sympathetic innervation to the cerebral circulation attenuates the CBF increase
      that accompanies increases in PaCO2 in sleep, particularly in REM sleep when CBF
      is high. DESIGN: Newborn lambs (n = 5) were instrumented to record CBF, arterial
      pressure (AP) intracranial pressure (ICP), and sleep-wake state (quiet
      wakefulness (QW), NREM, and REM sleep). Cerebral vascular resistance was
      calculated as CVR = [AP-ICP]/CBF. Lambs were subjected to 60-sec tests of
      hypercapnia (FICO2 = 0.08) during spontaneous sleep-wake states before (intact)
      and after sympathectomy (bilateral superior cervical ganglionectomy). RESULTS:
      During hypercapnia in intact animals, CBF increased and CVR decreased in all
      sleep-wake states, with the greatest changes occurring in REM (CBF 39.3% +/-
      6.1%, CVR -26.9% +/- 3.6%, P < 0.05). After sympathectomy, CBF increases (26.5%
      +/- 3.6%) and CVR decreases (-21.8% +/- 2.1%) during REM were less (P < 0.05).
      However the maximal CBF (27.8 +/- 4.2 mL/min) and minimum CVR (1.8 +/- 0.3 mm Hg/
      min/mL) reached during hypercapnia were similar to intact values. CONCLUSION:
      Hypercapnia increases CBF in sleep and wakefulness, with the increase being
      greatest in REM. Sympathectomy increases baseline CBF, but decreases the response
      to hypercapnia. These findings suggest that cerebral sympathetic nerve activity
      is normally withdrawn during hypercapnia in REM sleep, augmenting the CBF
      response.

PMID- 19090328
TI  - Hypoadiponectinemia is related to sympathetic activation and severity of
      obstructive sleep apnea.
AB  - STUDY OBJECTIVES: Hypoadiponectinemia is associated with cardiovascular morbidity
      and diabetes mellitus. We hypothesize that adiponectin may be downregulated in
      sleep apnea through various mechanisms, contributing to cardiometabolic risks.
      This study investigated the relationship between serum adiponectin and sleep
      disordered breathing and its potential determinants. DESIGN: Cross-sectional
      study. SUBJECTS AND SETTING: Adult men without prevailing medical comorbidity
      from the sleep clinic in a teaching hospital. MEASUREMENTS & RESULTS: One hundred
      thirty-four men underwent polysomnography, with mean age of 43.9 (9.8) years, and
      median apnea-hypopnea index (AHI) of 17.1 (5.7, 46.6). Overnight urine samples
      for catecholamines and blood samples for analyses of insulin, glucose and
      adiponectin levels from fasting subjects were taken. Insulin resistance was
      estimated by homeostasis model assessment (HOMA-IR). Magnetic resonance imaging
      was performed to quantify the amount of abdominal visceral fat. Serum adiponectin
      level, adjusted for age, body mass index, and visceral fat volume, was
      significantly lower in subjects with severe obstructive sleep apnea (AHI > or
      =30) compared with those with an AHI of less than 30: 4.0 (3.1, 5.4) versus 5.4
      (3.6, 7.9) microg/mL, P = 0.039. After we adjusted for adiposity, adiponectin
      levels remained negatively correlated with AHI (P = 0.037), arousal index (P =
      0.022), HOMA-IR/fasting insulin (P < 0.001), and urinary norepinephrine and
      normetanephrine (P < 0.008). In a multiple stepwise regression model, the
      independent determinants of adiponectin after adjustment for adiposity were HOMA
      IR (P < 0.001) and urinary norepinephrine and normetanephrine (P = 0.037).
      CONCLUSIONS: Adiponectin was suppressed in subjects with severe obstructive sleep
      apnea, independent of obesity. Adiponectin levels were determined by insulin
      resistance and sympathetic activation, factors that may be totally or partially
      attributed to sleep disordered breathing.

PMID- 19090330
TI  - Polysomnographic values in children undergoing puberty: pediatric vs. adult
      respiratory rules in adolescents.
AB  - STUDY OBJECTIVES: Polysomnographic respiratory events in children should be
      scored using pediatric respiratory rules. However, due to a lack of data on
      adolescents, recently revised rules allow children aged 13-18 years to be scored
      by adult or pediatric criteria. To clarify which criteria to use, we describe the
      evolution of respiratory events with Tanner stage, and we compare events in
      children aged 13-18 years with the new American Academy of Sleep Medicine adult
      and pediatric respiratory rules. DESIGN: Cross-sectional SETTING: Academic
      hospital PARTICIPANTS: Healthy subjects aged 8-18 years recruited for research
      purposes. INTERVENTIONS: Physical examination to determine Tanner stage,
      overnight polysomnogram, and determination of sex hormones. RESULTS: Sixty-eight
      subjects (Tanner 1-5) were studied, mean age [SD] = 13 +/- 3 years, median apnea
      hypopnea index (AHI)= 0.1 (range: 0-1.2)/h. The median percentages of total sleep
      time (TST) with SpO2 < 92% were 0.1 (0-4.2)%, and with end-tidal CO2 > 50 torr
      was 0.1 (0-88.6)%. Thirty-two subjects were aged 13-18 years, (Tanner 3-5). The
      difference between AHI scored by pediatric (median = 0 [0-0.9]/h) and adult
      (median = 0 [0 - 0.5]/h) criteria was statistically significant (P = 0.043), but
      not clinically relevant. CONCLUSIONS: Respiratory events in normal children aged
      8-18 years are rare and unrelated to Tanner stage. Adult or pediatric respiratory
      rules can be used for scoring polysomnograms in asymptomatic subjects approaching
      adulthood. Further studies are needed in symptomatic children within this age
      group.

PMID- 19090331
TI  - Presleep arousal and sleep disturbances in children.
AB  - STUDY OBJECTIVES: To determine if associations between presleep arousal and sleep
      disturbance reported in adults are also characteristic of children. DESIGN:
      Linear regression analyses examined whether somatic and cognitive presleep
      arousal predicted sleep disturbances. SETTING: Two inner city schools, London,
      U.K. PARTICIPANTS: One hundred twenty-three children aged 8 to 10 years, 49%
      boys, from ethnically diverse backgrounds. INTERVENTIONS: N/A. MEASUREMENTS AND
      RESULTS: Children completed the Sleep Self-Report and the Pre-sleep Arousal Scale
      (comprising somatic and cognitive subscales). Parents completed the Child Sleep
      Habits Questionnaire. In separate models, both somatic (beta = 0.44, P < 0.001,
      R2 = 0.19) and cognitive (beta = 0.48, P < 0.001, R2 = 0.23) presleep arousal
      predicted the Sleep Self-Report total score. Somatic (beta = 0.28, P <.01, R2 =
      0.08) and cognitive (beta = 0.37, P < 0.001, R2 = 0.14) arousal also predicted
      Sleep Self-Report insomnia items in separate models. These results were partially
      replicated when using the parent report of the Child Sleep Habits Questionnaire.
      When somatic and cognitive items were included in the same models, cognitive but
      not somatic arousal significantly predicted (most definitions of) sleep
      disturbance. CONCLUSIONS: Cognitive, and to a lesser extent somatic, presleep
      arousal appears to be associated with sleep disturbances in children. This
      suggests that further research into cognitive aspects of sleep disturbance in
      children is warranted-as incorporating this information into treatments may
      eventually prove fruitful.

PMID- 19090332
TI  - Perils of youth.

PMID- 19090333
TI  - A diagnostic pearl in allergic contact dermatitis to fragrances: the atomizer
      sign.
AB  - Allergic contact dermatitis (ACD) reactions to fragrances may present in a
      variety of ways because of exposure to these allergens from a wide range of
      sources. We describe a diagnostic pearl for this common ACD, primarily seen
      overlying the prominentia laryngea (Adam's apple) both in women and girls, which
      we have called the atomizer sign.

PMID- 19090334
TI  - Acute hemorrhagic edema of infancy: case reports and a review of the literature.
AB  - Acute hemorrhagic edema of infancy (AHEI) is an unusual form of leukocytoclastic
      vasculitis that affects children younger than 2 years and frequently is preceded
      by drug intake, vaccination, or a variety of infections. It is characterized by
      an abrupt onset of fever, purpuric lesions, and peripheral edema on the face and
      extremities that may be confused with other dermatoses. The course is benign with
      spontaneous resolution. We present 2 infants with AHEI and review the clinical
      manifestations, histology, and differential diagnosis.

PMID- 19090335
TI  - What is your diagnosis? Dermatofibrosarcoma protuberans.

PMID- 19090336
TI  - Harpist's finger: case report of a trauma-induced blister in a beginner harpist
      and review of string instrument-associated skin problems in musicians.
AB  - Musicians may develop skin problems resulting from playing their instruments.
      Dermatologic conditions in string players usually are secondary to allergic
      contact dermatitis (allergens include chromium, nickel, colophony,
      paraphenylenediamine, propolis, and exotic woods) and physical trauma (between
      either the fingers and the strings or the body and the instrument). A beginner
      harpist who developed harpist's finger--blister and subsequent callus of her left
      index finger from repeated trauma between the digit and the harp strings--is
      described, and string instrument-associated skin problems in musicians are
      reviewed.

PMID- 19090337
TI  - Benzoyl peroxide cleansers for the treatment of acne vulgaris: status report on
      available data.
AB  - Benzoyl peroxide (BPO) cleansers are commonly prescribed for treatment of acne
      vulgaris. In fact, they represent approximately half of all BPO prescriptions
      from dermatology practices. Data are limited on the ability of BPO cleansers to
      reduce counts of Propionibacterium acnes, impact on reduction and emergence of
      antibiotic-resistant P acnes strains, and efficacy for facial and truncal acne
      vulgaris. This article discusses available data on BPO cleanser formulations.

PMID- 19090338
TI  - Brooke-Spiegler syndrome with associated pegged teeth.
AB  - The occurrence of cylindromas, trichoepitheliomas, and spiradenomas completes the
      triad for Brooke-Spiegler syndrome (BSS). This combination represents a rare
      genetic syndrome with tumors expressing adnexal differentiation. Malignant
      transformation is rare but reported, and surgical excision is warranted to
      prevent turban tumor formation of the scalp. Genetic testing is encouraged, with
      mutations present on the cylindromatosis gene, CYLD, locus. The occurrence of
      pegged teeth in our patient was most interesting, as it has not been reported in
      the literature in patients with BSS.

PMID- 19090339
TI  - Bullous scabies: a diagnostic challenge.
AB  - Scabies, a contagious infestation associated with the human mite Sarcoptes
      scabiei var hominis, occasionally displays a spectrum of atypical cutaneous
      manifestations and associated symptoms. We describe an unusual case of scabies
      with bullae formation that mimicked bullous pemphigoid in clinical and
      histopathologic examination but not direct and indirect immunofluorescence
      examination.

PMID- 19090340
TI  - Lichen planus arising in radiation therapy treatment sites.
AB  - A 59-year-old woman with a history of metastatic breast cancer presented for
      evaluation of hyperpigmented, reticulated, pruritic plaques on her left arm and
      left thigh after undergoing localized radiation therapy to the left breast and
      left thigh. These painful plaques with surrounding erythema appeared to follow
      Blaschko lines and punch biopsy results were histologically consistent with
      lichen planus. Herein we report a case of radiation-induced lichen planus.

PMID- 19090341
TI  - Safety of a novel gel formulation of clindamycin phosphate 1.2%-tretinoin 0.025%:
      results from a 52-week open-label study.
AB  - Acne affects as many as 50 million individuals in the United States. Topical
      therapy combining a retinoid and an antibiotic is recommended as a first-line
      therapeutic option for mild to moderately severe acne. Although treatment for
      extended durations may be required, little long-term safety data on these
      combination therapies are available. This report summarizes the long-term safety
      and tolerability of a novel combination product for the treatment of acne
      vulgaris in participants 12 years and older. The combination treatment is a gel
      formulation containing a crystalline suspension of clindamycin phosphate 1.2%
      tretinoin 0.025% (CLIN/RA). Two cohorts participated in a long-term (up to 52
      weeks), multicenter, open-label, safety evaluation of CLIN/RA. Treatment duration
      was 6 months for the first cohort (N = 442) and 12 months for the second cohort
      (N = 213). Overall, the CLIN/RA gel was well-tolerated; 92%, 91%, and 94% of
      participants reported no itching, burning, or stinging, respectively. The most
      frequent adverse events were acne (29/442; 7% [usually a flare]), sunburn
      (12/442; 3%), hypersensitivity (7/442; 2%), contact dermatitis (5/442; 1%), and
      application-site desquamation (3/442; 1%). These results confirm the safety of
      CLIN/RA gel for mild to moderately severe acne. The CLIN/RA gel fixed-dose
      combination provided minimal adverse events and a favorable safety profile for 2
      agents with established efficacy for the treatment of acne vulgaris.

PMID- 19090342
TI  - Decisions in choosing a career in academic dermatology.

PMID- 19090343
TI  - Successful treatment of moderate to severe melasma with triple-combination cream
      and glycolic acid peels: a pilot study.
AB  - Triple-combination (TC) cream is a stable combination of fluocinolone acetonide
      0.01%, hydroquinone 4%, and tretinoin 0.05%, and currently is the only US Food
      and Drug Administration-approved drug for the topical treatment of melasma.
      Furthermore, it is the only US Food and Drug Administration-approved product
      containing hydroquinone. Anecdotal evidence suggests that improvements in melasma
      can be achieved with a multifactor approach involving TC cream with a variety of
      procedures. A pilot study was designed to evaluate the efficacy and safety of
      sequential treatment with TC cream and a series of glycolic acid (GA) peels in
      participants with moderate to severe melasma. Participants were treated with TC
      cream for 2 weeks before the alternating sequential treatment cycles with TC
      cream and GA peels began. A total of six 2-week cycles of TC cream and 5 GA peels
      were used. Efficacy and safety evaluations were conducted at weeks 6 and 12.
      Investigator global assessment (IGA) ratings indicated that 1 of 20 participants
      (5%) had achieved treatment success (clear/almost clear) as early as week 6 and
      most participants had achieved treatment success by week 12 (65% [13/20]; P <
      .001 vs baseline). Objective absorption spectrometry measurements of the
      difference in melanin for involved versus uninvolved skin confirmed that
      hyperpigmentation was significantly reduced in participants at weeks 6 and 12
      compared with baseline (P < .001 for both). Investigator and participant
      evaluations revealed that most participants (> or = 90%) showed improvement
      (excellent improvement, much improved, improved) by week 12 with alternating
      sequential treatment with TC cream and GA peels. Furthermore, the results of this
      study indicated that sequential treatment with TC cream and GA peels was well
      tolerated.

PMID- 19090344
TI  - Oral contraceptive-induced high blood pressure is prevented by renin-angiotensin
      suppression in female rats but not by sympathetic nervous system blockade.
AB  - The use of oral contraceptive (OC) steroids is associated with high blood
      pressure, although mechanisms responsible are still unclear. This study sought to
      investigate the possible roles that renin-angiotensin system (RAS) and
      sympathetic nervous system (SNS) may play in the development of OC-induced
      hypertension. Administration of OC led to significant increases in blood
      pressure, heart weight and significant decrease in urinary output in OC-treated
      and OC+clonidine-treated groups but not in OC+captopril-treated group. The
      pressor response to angiostensin II was significantly greater in the OC-treated
      rats than in the control rats. However, the pressor responses induced by
      norepinephrine were not significantly affected by OC administration. The results
      of the present study demonstrate that OC-induced high blood pressure is
      associated with cardiac hypertrophy, enhanced pressor response to angiotensin II
      and preserved pressor response to sympathetic activation. The study also suggests
      that the development of the OC-induced hypertension and cardiac hypertrophy is
      mediated by RAS, but not by SNS.

PMID- 19090345
TI  - Vasosensory responses elicited by Indian red scorpion venom last longer than
      capsaicin-induced responses.
AB  - The present study was conducted to compare the time-related cardiorespiratory
      changes occurring after the injection of Mesobuthus tamulus (BT; 1 mg/kg) venom
      and capsaicin (1.2 ng/kg) in the peripheral end of femoral artery in urethane
      anaesthetised rats. Blood pressure (BP), electrocardiogram (for heart rate; HR)
      and respiratory movements were recorded for 60 min after venom/capsaicin intra
      arterially. Minute ventilation (MV) was computed by using appropriate
      calibrations. After intraarterial injection of BT venom, there was immediate
      (within 2 sec) increase in respiratory rate (RR) and MV which reached to 40%
      within 30 sec, followed by a 40% decrease in RR without any change in MV.
      Further, there was sustained increase in RR (50%) and MV (65%) up to 60 min. The
      BP began to increase at 40 sec, peaking at 5 min (50%) and remained above the
      initial level up to 60 min. The bradycardiac response began after 5 min which
      peaked (50% of the initial) at 25 min and remained at that level up to 60 min. In
      capsaicin treated group, there was immediate hyperventilatory (increase in RR and
      MV) changes within 2 sec which returned to the initial level within 2 min and
      remained at that level up to 60 min. The capsaicin-induced hypotensive response
      began within 5 sec which returned to the initial level by 5 min and remained at
      that level throughout. Capsaicin did not produce any change in HR. These
      observations suggest that intraarterial injection of BT venom produces prolonged
      cardiorespiratory alterations as compared to the capsaicin-induced responses.

PMID- 19090346
TI  - Processing of multimer FMD virus VP1-2A protein expressed in E. coli into
      monomers.
AB  - Expressions of several genes in bacteria were carried out by independent
      promoter. However, in case of eukaryotes ribosome skipping and introduction of
      IRES are employed as alternative to multiple translation initiation. Foot and
      mouth disease virus (FMDV) 2A peptide has been widely used for co-expression of
      multiple genes in eukaryotic, plant and mammalian systems. The 18 amino acid 2A
      peptide of FMDV facilitates efficient co-translational dissociation of the
      polyprotein into discrete protein products. To study the role of 2A in multimeric
      protein production a construct consisting of tandem repeat of 4 units of C-
      terminal VP1 linked through 2A sequence was made and expressed in E. coli. Along
      with tetramer protein, trimer, dimer and monomer proteins were produced.
      Stability studies showed that the tetramer protein was cleaved to smaller monomer
      on storage. The results provide scope for using FMDV 2A for expressing multiple
      genes under a single promoter in prokaryotes.

PMID- 19090347
TI  - In vitro brain tyrosine hydroxylase activation in catfish Heteropneustes fossilis
      (Bloch): seasonal changes in involvement of cAMP-dependent protein kinase A and
      Ca2+ -dependent protein kinase C.
AB  - In the present in vitro study, the involvement of cAMP dependent-protein kinase A
      (PKA) and calcium-dependent protein kinase C (PKC) in the regulation of forebrain
      (telencephalon and hypothalamus) tyrosine hydroxylase (TH) activity was
      demonstrated during the reproductive seasons of the female catfish H. fossilis.
      In the concentration studies conducted in prespawning phase, cAMP (0.05 nM, 0.5
      nM, 1 mM and 2.0 mM) or the phosphodiesterase inhibitor isobutylmethylxanthine
      (IBMX-0.5-2.0 mM) stimulated enzyme activity. Likewise, the incubation of the
      enzyme preparations with the cAMP dependent-protein kinase A inhibitor H-89 (1
      and 10 microM) and PKC inhibitor calphostin C (cal C; 1 and 10 microM) inhibited
      enzyme activity in a concentration-dependent manner. In seasonal studies, the
      incubation of the enzyme preparations with cAMP (1 mM), IBMX (1 mM), H-89 (10
      microM) and cal-C (10 microM) produced season-dependent effects on enzyme
      activity. The stimulatory effect of cAMP and IBMX and the inhibitory effect of H
      89 and cal C were greater in the resting and spawning phases. The results suggest
      the involvement of both signal transduction pathways in TH activation vis-a-vis
      catecholaminergic activity with a more dominant role by the cAMP-PKA pathway.

PMID- 19090348
TI  - Possible role of citalopram and desipramine against sleep deprivation-induced
      anxiety like-behavior alterations and oxidative damage in mice.
AB  - Sleep is an essential physiological process for maintaining physical, mental, and
      emotional health. Sleep deprivation and associated disorders like depression and
      anxiety are one of the major problems now-days. The present study was designed to
      explore the neuroprotecitve effect of citalopram and desipramine on 72 hr sleep
      deprivation-induced behavioral alterations and oxidative damage in mice. Various
      behavioral tests (plus maze, zero maze, mirror chamber, actophotometer), body
      weight followed by oxidative parameters (malondialdehyde level, glutathione,
      catalase, nitrite and protein) were assessed. Treatment with citalopram (5 and 10
      mg/kg, ip) and desipramine (10 and 20 mg/kg, ip) for 5 days significantly
      improved locomotor activity, anti-anxiety like behavior in all paradigms tasks
      (mirror chamber, plus maze, zero maze) as compared to control (72 hr sleep
      deprived). Biochemically, citalopram and desipramine treatment significantly
      restored depleted reduced glutathione, catalase activity, attenuated raised lipid
      peroxidation and nitrite level as compared to control (72 hr sleep-deprived)
      animals. Results of present study suggest that citalopram (5 and 10mg/kg, ip) and
      desipramine (10 and 20 mg/kg, ip) have neuroprotective effect against sleep
      deprivation-induced behavior alteration and oxidative damage in mice.

PMID- 19090349
TI  - Wound healing activity of Sesamum indicum L seed and oil in rats.
AB  - The seeds of S. indicum L (Pedaliaceae) are used traditionally in the folklore
      for the treatment of various kinds of wounds. The present study was undertaken to
      verify the effect of S. indicum seeds and its oil on experimentally induced
      excision wound, incision wound, burn wound and dead space wound models in rats.
      Aloe vera was used as standard wound healing agent. A formulation of seeds and
      oil was prepared in carbopol at 2.5% and 5% concentrations and applied to the
      wounds. In the excision and burn wound models, the so treated animals showed
      significant reduction in period of epithelization and wound contraction (50%). In
      the incision wound model a significant increase in the breaking strength was
      observed. Seeds and oil treatment (250 mg and 500 mg/kg; po) in dead space wound
      model, produced a significant increase in the breaking strength, dry weight and
      hydroxyproline content of the granulation tissue. The results suggest that S.
      indicum seeds and oil applied topically or administered orally possesses wound
      healing activity.

PMID- 19090350
TI  - Screening of natural phenolic compounds for potential to inhibit bacterial cell
      division protein FtsZ.
AB  - FtsZ plays an important role in bacterial cell division by polymerizing to form
      the Z ring at the site of cytokinesis. Phytochemicals are known to disrupt
      bacterial cell division through inhibition of FtsZ assembly. In the present study
      phytochemicals like eugenol, trans-cinnamic acid, 4-formyl cinnamic acid,
      naringenin and caffeic acid were were tested for their potential to inhibit cell
      division. Effect of these antimicrobial compounds on the growth of E. coli was
      determined and the inhibition of FtsZ assembly in vitro was investigated. The
      present study revealed trans-cinnamic acid as the most potent inhibitor of FtsZ
      assembly.

PMID- 19090351
TI  - Efficacy of 4-methyl-7-hydroxy coumarin derivatives against vectors Aedes aegypti
      and Culex quinquefasciatus.
AB  - 4-Methyl-7-hydroxy coumarin is considered as a lead molecule as a biopesticide.
      Its mono bromo and tribromo derivatives were synthesized. Two more derivatives
      were synthesized by acylation. Compound 1 (3,6,8-tribromo-7-hydroxy-4-methyl
      chromen-2-one) was found to be the most potent against IVth instar larvae of C.
      quinquefasciatus and A. aegypti the LC50 being 1.49 and 2.23 ppm respectively. It
      showed 100% larval mortality at 25 ppm against A. aegypti and at 10 ppm against
      C. quinquefasciatus. Compounds 1 and 2 (3,6,8-tribromo-7-hydroxy-4-methyl-chromen
      2'-oxo-2H-chromen-7-yl acetate) showed remarkable ovicidal activity. Significant
      reduction of 80-85% hatching of eggs of both mosquito species was observed at the
      highest dose of 100 ppm. The hatched larvae showed 100% mortality in the
      successive instars. Compounds 3 and 4 (3-bromo-7-hydroxy-4-methyl-chromen-2-one
      and 3-bromo-4-methyl-2'-oxo-2H-chromen-7-yl acetate) showed moderate activity
      against both mosquito species.

PMID- 19090352
TI  - Assembly of recombinant coat protein of sugarcane streak mosaic virus into
      potyvirus-like particles.
AB  - Coat protein (CP) gene of sugarcane streak mosaic virus-AP isolate (SCSMV-AP) was
      expressed in E. coli and recombinant CP (SCSMV-AP rCP) was purified by linear
      sucrose density gradient centrifugation. Observation of purified SCSMV-AP rCP
      under electron microscope revealed the presence of potyvirus-like particles
      (PVLPs). The assembled particles were shown to encapsidate CP gene transcripts by
      slot-blot hybridization.

PMID- 19090353
TI  - Nurses told to radically expand HIV test levels.

PMID- 19090354
TI  - Coming clean on infection control.

PMID- 19090355
TI  - Until safety alerts are acted on, patients will still be put in unnecessary
      danger.

PMID- 19090356
TI  - 'People who are obese need our help and support'.

PMID- 19090357
TI  - 'Drunken teenagers need to respect one another'.

PMID- 19090359
TI  - Guidelines focus on improving patient safety in mental health.

PMID- 19090358
TI  - Safety alerts failing to reach the frontline.

PMID- 19090360
TI  - Exploring the anatomy and physiology of ageing. Part 10--muscles and bone.

PMID- 19090362
TI  - Using poster presentations in nursing education.
AB  - This article outlines how student nurses evaluated the introduction of a poster
      presentation within a module. It highlights how such a strategy can: make
      learning more enjoyable; disseminate information to peers and practice staff; and
      be used as a teaching aid for patients.

PMID- 19090361
TI  - Nutrition for people with stomas 1: overview of issues.
AB  - This is the first in a two-part unit examining nutrition for people with stomas.
      It outlines the three main types of stomas--colostomy, ileostomy and urostomy-
      and the principles of a healthy diet in general.

PMID- 19090363
TI  - Implementing a school-based HPV vaccination programme.
AB  - BACKGROUND: The Department of Health launched a national human papillomavirus
      immunisation programme for girls aged 12-13 years in September 2008. AIM: To
      assess the feasibility and acceptability of implementing a school-based
      programme. METHOD: HPV vaccination was offered over one academic year by two PCTs
      in 36 schools to 12-13-year-old girls, using different implementation plans.
      RESULTS: At parent information evenings, the questions most often raised related
      to vaccine safety. In PCT 2, first-dose vaccine uptake was 78.7% (1,292), higher
      than the 59.8% (706) achieved in PCT 1. Using a late recall system and accepting
      late consenters in PCT 2 was associated with higher uptake, but led to one in
      five girls being outside the school schedule. CONCLUSION: This study suggests
      uptake can be improved by achieving a high initial consent rate, accepting late
      consenters and adopting a flexible policy to maintain high coverage across all
      three doses.

PMID- 19090364
TI  - Road safety is no accident.

PMID- 19090365
TI  - Angioplasty to replace thrombolysis as first-line treatment for heart attack.

PMID- 19090366
TI  - Targeting the drinking culture.

PMID- 19090367
TI  - Treating patients who self-harm.

PMID- 19090368
TI  - Changes and challenges ahead for emergency nurses.

PMID- 19090369
TI  - A global perspective.

PMID- 19090370
TI  - Services for people who self-harm.

PMID- 19090371
TI  - A forum for improvement.

PMID- 19090372
TI  - The ABC of mental health.

PMID- 19090373
TI  - Practice makes perfect. Monteggia's fracture.

PMID- 19090374
TI  - Knife crime education.

PMID- 19090375
TI  - Improving end-of-life care in emergency departments.

PMID- 19090376
TI  - Board's eye view.

PMID- 19090377
TI  - Training for war: teaching and skill-retention for the deployed surgical team.

PMID- 19090378
TI  - Pre-hospital antibiotic administration.

PMID- 19090379
TI  - Use of nasogastric tubes in trauma patients--a review.
AB  - Traditionally, suspected basal skull fractures have been considered a relative
      contra-indication to inserting a nasogastric tube (NGT). In patients with basal
      skull fractures the Advanced Trauma Life Support protocol recommends that an
      orogastric tube (OGT) be inserted rather than a nasogastric tube (NGT). This
      article reviews the available literature. We conclude that in patients with
      suspected or confirmed basal skull fractures numerous case reports confirm that
      nasogastric tube insertion may lead to intracranial placement which, although the
      causal relationship is unclear, is associated with patient death.

PMID- 19090380
TI  - Forward trauma surgery in Afghanistan: lessons learnt on the modern asymmetric
      battlefield.
AB  - The deployment of 16 Air Assault Brigade to Helmand Province, Afghanistan in
      April-October 2006 was supported by a two -surgeon Field Surgical Team (FST)
      embedded within a 25 bed medical facility. We report the summative operative
      experience of the FST in order to analyse workload, case-mix and outline future
      training requirements. Within this period, 138 patients underwent 255 theatre
      episodes and 322 surgical procedures. 106 of the 138 patients requiring surgery
      were battle-injured. Surgical procedures undertaken involved wound excision (95),
      major amputation (9), laparotomy (9), application of external-fixation/skeletal
      traction (6), thoracotomy (4), plaster application (6), dural repair (2), and one
      tracheostomy with 13 other procedures. Procedures undertaken at subsequent
      surgery included delayed primary closure (65), split skin graft (7), wound
      excision (5), tendon repair (3) and 32 others. Complications included two
      patients with delayed reactionary haemorrhage/ post-surgical bleeding requiring
      re-operation. There was one in-hospital death. Thirty-two patients underwent
      surgery to treat disease or non-battle injury (DNBI), including 9 patients with
      major burns who required 26 procedures for burn excision and primary skin
      grafting. Many of the operations required the deployed team to operate outside of
      their normal NHS comfort zone. The experiences and lessons learnt and re-learnt
      by this surgical team should be part of our institutional memory.

PMID- 19090381
TI  - A treatment algorithm for mass heat casualties.
AB  - Although thankfully rare,heat related illness has significant implications for
      the effective fighting force available to commanders. This is especially
      pertinent in the current theatres of operations, as previously soldiers have not
      routinely been subjected to the rigors of operating in hot climates. In addition
      to Iraq and Afghanistan, various training exercises are undertaken throughout the
      world where extreme temperatures may be encountered. Individual medical officers
      may be faced with heat casualties remote from all but the most basic facilities
      or the number of heat casualties may overwhelm limited resources. We present a
      simple treatment algorithm that has been used successfully in the treatment of
      mass heat casualties.

PMID- 19090382
TI  - Airway management at floor level: a comparison of tracheal intubation using the
      Macintosh and Airtraq laryngoscopes.
AB  - Practitioners providing pre-hospital care during civilian practice and on
      military operations may be required to perform airway management and tracheal
      intubation at floor level. It has been shown that intubation using the Airtraq
      laryngoscope is easier to learn than standard Macintosh laryngoscopy. We
      hypothesised that the Airtraq would be easier to use and have shorter intubation
      times than Macintosh intubation. Sixty volunteers attending a medical conference
      with no prior Airtraq experience, who were skilled in pre-hospital Macintosh
      intubation, were recruited. Each was required to intubate an anatomically correct
      manikin at floor level using a Macintosh and Airtraq laryngoscope. The Airtraq
      was found to be superior in ease of use (VAS 30 mm, P < 0.001), had a shorter
      total intubation time (19.4seconds) and a higher intubation success rate (P =
      0.012) than the Macintosh laryngoscope (VAS 50 mm, 20.4 seconds). Rotating the
      tracheal tube 90 degrees anticlockwise during loading into the guiding channel,
      made the Airtraq intubation easier (VAS 30 mm, P = 0.001) and faster (19.4
      seconds, P < 0.001) than with standard orientation of the tube (VAS 40 mm, 25.3
      seconds). Airtraq intubation may prove to be easier than Macintosh intubation,
      when utilised in the clinical pre-hospital setting, though randomised controlled
      clinical trials are required to confirm this.

PMID- 19090383
TI  - Why military personnel fail to keep medical appointments.
AB  - OBJECTIVES: Failure to keep medical appointments, commonly referred to as 'Did
      Not Attend' (DNA), is a frequent problem in both primary and secondary health
      care and leads to a waste of valuable resources. Although the reasons for DNA
      within the general population are well documented, little is known about this
      behaviour amongst people serving in the armed forces. In this paper we report the
      findings of a questionnaire-based study investigating the reasons why military
      personnel fail to keep hospital appointments. METHOD: A postal questionnaire
      asking questions about the reasons for not attending the appointment and how they
      perceived the condition for which treatment had been sought, were sent to 167
      military patients known to have missed appointments in either a hospital
      outpatient department or regional rehabilitation unit. 162 controls, who attended
      appointments, were also sent a questionnaire asking them about factors leading to
      their appointment and how they perceived the condition that they attended the
      appointment for. Illness perception was measured using a previously validated
      Illness perception Questionnaire (IPQ-R). The controls were matched by rank,
      gender and corps. RESULTS: The overall response rate was 51.5%, with 46% response
      in the DNA group and 55% in the controls. A previous history of hospital DNA
      (though not DNA in primary care) and attempting to change the appointment date
      were associated with DNA (p = 0.01). Those who received a reminder about the
      appointment were less likely to DNA (p < or = 0.001). Although patients who
      perceived their condition to be less important were more likely to fail to attend
      their appointment (p = 0.01), illness perception as measured on the IPQ-R, was
      not associated with appointment attendance. The most frequent reasons cited for
      missed appointments were due to administrative problems, with many (38%)
      respondents being simply unaware that they had an appointment at all or believing
      that they had cancelled it (14%). Forgetting the appointment (8%) or mixing up
      the date (21%) were also cited by respondents as reasons for not attending. Only
      11% of respondents gave reasons that were specific to a military population, most
      frequently being on exercise at the time of their appointment. Demographic
      differences such as age and gender, and practical factors such as appointment
      day, distance travelled, method of appointment notification, or type of hospital
      were not found to be associated with attendance. CONCLUSION: The most common
      reasons for not attending appointments were due to administrative error and an
      inability amongst patients to recall the correct date of the appointment. Whilst
      efforts to improve attendance through various reminder systems have been found to
      be effective in the short term at least, improvements in the efficiency of
      appointment administration is likely to generate a reduction in DNA and in turn
      will reduce the wastage of resources.

PMID- 19090384
TI  - Using body weight as a pre-hospital fluid infusion device: the relationship
      between under-body position and flow rate.
AB  - This study was designed to identify the most effective underbody position when
      using the patient's own body weight as an infusion device. Twenty volunteers had
      an air-less 500 ml bag of saline located at various under-body positions. Mean
      pressures and flow rates through a 14G cannula were measured in vitro at room
      temperature. Locating the fluid bag at the buttock cleft delivered the highest
      mean flow rate at 135 ml/min. This underbody position may provide flow rates
      sufficient to achieve the clinical aim of fluid resuscitation in the military pre
      hospital environment.

PMID- 19090385
TI  - BATLS/BARTS/BBTLS training for Swedish Armed Forces medical personnel--a ten year
      retrospective study.
AB  - OBJECTIVE: The British BATLS/BARTS concept was introduced in Sweden in 1998.
      Perceived changes within the student group, regarding purposes for taking the
      course and previous trauma training were the subject of the study. METHODS:
      Records from all Swedish courses during 1998-2007 were examined and analyzed.
      RESULTS: In all, 61 courses with a total of 1254 students were conducted. Among
      the participants were 295 doctors, 764 nurses, 176 medical orderlies and 19
      belonging to other categories. The course has by time become a pre-mission
      course. Also, a large number of the students now have previous (often civilian)
      trauma life support training. CONCLUSION: When the British BATLS/BARTS concept
      was introduced in Sweden ten years ago, the general level of trauma training
      among medical personnel was inadequate for the wartime needs of the Armed Forces.
      Today, the majority of individuals selected for international service already
      have previous trauma life support training. This has led to the courses now being
      aimed mainly at improving their knowledge of the tactical medical skills
      particular to the environment in which they will serve.

PMID- 19090386
TI  - Management of shoulder instability in a military population.
AB  - OBJECTIVES: Recurrent instability is common after shoulder dislocation in the
      young, particularly those engaged in physical jobs or sport. The management of
      recurrent traumatic shoulder instability is predominantly operative. However, the
      best method of surgery i.e. open or arthroscopic is still a matter of debate. We
      have developed an algorithm to decide on the choice of surgery and the aim of
      this study is to report this and compare the two different groups of military
      patients. METHODS: A retrospective review of all shoulder stabilisations
      performed on military personnel, by a single surgeon, between August 2004 and
      August 2005 at a district general hospital serving both military and civilian
      population was undertaken. The presentation, clinical and operative findings were
      noted and compared in the groups treated by arthroscopic or open stabilisation.
      RESULTS: Using our protocol 39 shoulder stabilisations were performed in military
      personnel. Of the shoulders, 25 (64%) underwent arthroscopic and 14 (36%)
      underwent open stabilisation. The indication for surgery was more than 2 episodes
      of shoulder dislocation. Open surgery was found to be more common in those who
      had their first dislocation at a younger age. Bilateral shoulder laxity was the
      most common indication to choose the open method. Both open and arthroscopic
      stabilisation gave good results in the high demand military population. Only one
      patient had recurrent instability after arthroscopic procedure. However, this was
      not statistically significant when compared with open stabilisation.

PMID- 19090387
TI  - Getting the best of both worlds--clinical excellence at a peripheral unit.
AB  - Audit of hospital practice in remote areas and military practice indicates that
      it is possible to provide a high degree of patient safety with the advantages of
      care close to home in a small hospital with less than 100 beds. However such an
      approach requires strict attention to training and retraining, good clinical
      networking, attention to quality control and a well defined system for
      identifying those patients who need to be transferred to a specialist centre.

PMID- 19090388
TI  - Femoral neck stress fractures in military personnel--a case series.
AB  - Femoral neck stress fractures (FNSF) are uncommon, representing 5% of all stress
      fractures. In military personnel, FNSF represents one of the more severe
      complications of training, which can result in medical discharge. Clinical
      examination findings are often non-specific and plain radiography may be
      inconclusive--leading to missed or late diagnosis of FNSF This paper highlights
      the significance of FNSFs in military personnel and alerts physicians to the
      potential diagnosis. We identified all military recruits, aged 17 to 26, who
      attended the Infantry Training Centre (Catterick, U.K.), over a four-year period
      from the 1st July 2002 to 30th June 2006, who had suffered a FNSF. The medical
      records, plain radiographs, bone scans and MRIs of the recruits were
      retrospectively reviewed. Of 250 stress fractures 20 were of the femoral neck;
      representing 8% of all stress fractures and an overall FNSF rate of 12 in 10,000
      military recruits. FNSFs were most prevalent amongst Parachute Regiment recruits
      (1 in 250, p < 0.05). Onset of symptoms was most commonly between weeks 13-16 of
      training. The majority (17/20, 85%) of FNSFs were undisplaced, these were all
      treated conservatively. Three FNSFs were displaced on presentation and were
      treated surgically. Overall, the medical discharge rate was 40% (8/20). FNSFs are
      uncommon and the diagnosis remains a challenge to clinicians and requires a high
      index of suspicion in these young athletic individuals. In such individuals early
      referral for MRI is recommended, to aid prompt diagnosis and treatment and to
      prevent more serious sequelae.

PMID- 19090389
TI  - D-day on board a tank landing ship: meat, cheese and blood transfusion.
AB  - Tank Landing Ships were used as evacuation station hospitals during D-Day of
      World War Two. This historical vignette describes how difficulties were overcome
      in blood transfusion and trauma surgery aboard these ships. Their place in the
      evacuation chain is discussed in relation to previous experiences in military
      medicine.

PMID- 19090390
TI  - An unusual case of sinusitis.
AB  - BACKGROUND: Common Variable Immunodeficiency (CVID) is the commonest form of
      severe antibody deficiency. It is characterized by reduced levels of IgG (<400
      mg/dL) and low IgA and/or IgM levels, recurrent bacterial infections, impaired
      antibody responses despite the presence of B Cells and normal or near normal T
      immunity in 60% of patients. There is a high mortality from infections without
      treatment. The main stay treatment is to replace the immunoglobulins. CASE
      PRESENTATION: We describe a British soldier with a 10 year history of recurrent
      chest infections, sinusitis and otitis media. He repeatedly presented 2 to 3
      times a year complaining of either a green nasal discharge or a cough productive
      of yellow/green sputum. He presented three years ago with severe sinusitis which
      resulted in investigations highlighting hypogammaglobulinaemia. Subsequently he
      was started on immunoglobulin therapy with Flebogamma 40 g three weekly.
      RECOMMENDATIONS: Despite being a relatively rare condition, CVID when diagnosed,
      can be easily treated and improve patients' prognosis. Medical Officers should be
      aware of the condition as a differential diagnosis for individuals presenting
      with recurrent infections.

PMID- 19090391
TI  - Pleomorphic adenoma arising from accessory parotid tissue presenting as
      dysphonia.
AB  - This article describes an unusual presentation of pleomorphic adenoma arising
      from accessory parotid tissue. A patient who had recently been diagnosed with
      Parkinson's disease, presented with worsening dysphonia. Magnetic resonance
      imaging and ultrasound guided core biopsies confirmed the diagnosis and the mass
      was removed by extra capsular dissection through a lip split mandibulotomy
      approach. This case confirms the need for careful examination of the oropharynx
      in patients with preexisting neurological conditions that develop speech
      disturbance. It also demonstrates the importance of these imaging techniques in
      the diagnosis of parapharyngeal lesions.

PMID- 19090392
TI  - A case of external ophthalmomyiasis in a deployed U.K. soldier.
AB  - Infestation of the eye by larval fly forms (ophthalmomyiasis) is rarely seen in
      the Western world. We present the case of a 21 year old British soldier who
      developed external ophthalmomyiasis during an operational tour of southern
      Afghanistan. This case report and discussion illustrates the potential for
      ophthalmomyiasis in personnel deployed to this theatre; the possibility of
      infestation without an identifiable episode of exposure; the importance of proper
      assessment and follow-up in order to identify sight-threatening complications;
      and the balance between optimal patient care and the risks inherent to casualty
      evacuation demanded by modern day stability operations.

PMID- 19090393
TI  - Anaesthesia.

PMID- 19090394
TI  - Heat stroke and its allied conditions. 1939.

PMID- 19090395
TI  - Sir Frederick Treves.

PMID- 19090396
TI  - Methoxyflurane.

PMID- 19090397
TI  - Hospex--a valuable training and educational opportunity.

PMID- 19090398
TI  - The youngest Victoria Cross: the award of the Victoria Cross to Andrew
      Fitzgibbon.

PMID- 19090399
TI  - Spinal anaesthetic with patient wearing enhanced combat body armour.

PMID- 19090400
TI  - Orofacial pain and motor control: the history of 3 giants in orofacial
      neuroscience--Sessle, Lund, and Hannam.

PMID- 19090401
TI  - From pain to movement: a tribute to professor Barry J. Sessle.
AB  - This tribute article to Professor Barry J. Sessle summarizes the 6 presentations
      delivered at the July 1, 2008 symposium at the University of Toronto. The
      symposium honored 3 "giants" in orofacial neuroscience, Professors B. J. Sessle,
      J. P. Lund, and A. G. Hannam. The 6 presentations paying tribute to Sessle
      spanned the period from the early phase of his career up to some of his most
      recent studies with colleagues in Asia, Europe, and Australia as well as Canada.
      The studies have included those providing an improved understanding of the
      cortical control of sensory inputs in pain perception (presented by R. Dubner)
      and in the control of mastication and swallowing, as well as brainstem mechanisms
      of orofacial pain (K. Iwata, G. Murray). His current activities in his laboratory
      and in Denmark are also highlighted (L. Avivi-Arber, P. Svensson). The potential
      transfer of basic research discoveries toward drug development in pain control
      that stem from some of his research is also described (B. Cairns). The final
      section of the paper includes a commentary from Professor Sessle.

PMID- 19090402
TI  - From movement to pain: a tribute to professor James P. Lund.
AB  - This tribute article to Professor James P. Lund stems from 6 of the presentations
      delivered at the July 1, 2008, symposium that honored 3 "giants" in orofacial
      neuroscience: B. J. Sessle, A. G. Hannam, and J. P. Lund. It was noted that soon
      after his training as a dentist in Australia, Jim Lund became interested in
      research. At the time he decided to do a PhD, there was a lot of discussion about
      how rhythmic movements were programmed. The early belief, based on Sherrington's
      studies of motor systems, was that these movements were simply an alternating
      series of reflexes. In the late 1960s and early 1970s, some still shared this
      belief, whereas others favored Graham Brown's hypothesis that repetitive
      movements were centrally programmed and did not depend on reflexes triggered by
      sensory inputs. There was no strong evidence then for either scenario except for
      the rhythmic movements of respiration. Lund's pioneering work during his PhD
      proved the existence of a central pattern generator (CPG) for mastication in the
      brainstem. Since then he has been interested in understanding how CPGs function
      and how sensory feedback works to adjust the motor patterns that they produce.
      Sections in this tribute article to Lund are written by some of his close
      collaborators and reflect the evolution of his work throughout the years. The
      first 4 presentations in this article (by K.-G. Westberg, D. McFarland, A. Kolta,
      and C. Stohler) highlight various aspects of these interests, and the final 2
      presentations (by J. Feine and A. Woda) focus especially on clinical aspects of
      Lund's interests. The last section of this article is a final commentary from
      Professor Lund.

PMID- 19090403
TI  - From movement to models: a tribute to professor Alan G. Hannam.
AB  - This tribute article to Professor Alan G. Hannam is based on 7 presentations for
      him at the July 1, 2008 symposium honoring 3 "giants" in orofacial neuroscience:
      Professors B. J. Sessle, J. P. Lund, and A. G. Hannam. This tribute to Hannam's
      outstanding career draws examples from his 40-year academic career and spans
      topics from human evolution to complex modeling of the craniomandibular system.
      The first presentation by W. Hylander provides a plausible answer to the
      functional and evolutionary significance of canine reduction in hominins. The
      second presentation, by A. McMillan, describes research activities in the field
      of healthy aging, including findings that intensity-modulated radiotherapy
      improves the health condition and quality of life of people with nasopharyngeal
      carcinoma in comparison to conventional radiotherapy. The developments in dental
      imaging are summarized in the third paper by E. Lam, and an overview of the bite
      force magnitude and direction while clenching is described in the fourth paper by
      M. Watanabe. The last 3 contributions by G. Langenbach, I. Staveness, and C. Peck
      deal with the topic of bone remodeling as well as masticatory system modeling,
      which was Hannam's main research interest in recent years. These contributions
      show the considerable advancements that have been made in the last decade under
      Hannam's drive, in particular the development of an interactive model comprising,
      in addition to the masticatory system, also the upper airways. The final section
      of the article includes a final commentary from Professor Hannam.

PMID- 19090404
TI  - Temporomandibular joint and muscle disorder-type pain in U.S. adults: the
      National Health Interview Survey.
AB  - AIMS: To compare prevalences of self-reported temporomandibular joint and muscle
      disorders (TMJMD)-type pain in the 2002 U.S. National Health Interview Survey
      (NHIS) by age and gender for non-Hispanic whites (Caucasians) and non-Hispanic
      blacks (African Americans). METHODS: Data from the 2002 NHIS included information
      on gender, age, race, ethnicity, education, and TMJMD-type pain. Rao-Scott survey
      chi-square and survey logistic regression analyses using sampling weights and
      accounting for the complex design were used to analyze variables relating to
      prevalences. RESULTS: A total of 30,978 people, 17,498 females and 13,480 males,
      20,389 non-Hispanic whites and 4179 non-Hispanic blacks, were included. The
      overall prevalence of TMJMD-type pain was 4.6%, with 6.3% for women and 2.8% for
      men. However, based on age, a significant but modest racial/ethnic difference
      emerged after adjusting for socioeconomic status. For non-Hispanic white women up
      to age 50, the prevalence was approximately 7% to 8%, but it decreased after age
      55. Non-Hispanic black women had much lower prevalence at younger ages
      (approximately 4% at 25 to 34 years), which increased thereafter up to 55 to 64
      years of age. A similar racial pattern seemed to emerge for non-Hispanic black
      men, with the lowest prevalence at ages 25 to 34 years, while non-Hispanic white
      men had higher prevalences. Overall, however, age seemed to play more of a role
      in women than men. CONCLUSION: This is the first report of findings from a
      nationally representative US sample for TMJMD-type pain by age and
      race/ethnicity. TMJMD-type pain differed significantly by race, age, and gender
      after adjusting for socioeconomic status.

PMID- 19090405
TI  - Chronic orofacial pain in southern Chinese people: experience, associated
      disability, and help-seeking response.
AB  - AIMS: To investigate chronic orofacial pain experience, psychosocial impact, and
      help-seeking response in adult Chinese people in Hong Kong. METHODS: A cross
      sectional population-based telephone interview survey identified 1352 randomly
      selected people aged > or =18 years. Standard questions were asked about current
      or episodic and prior (> or = 6 months) experience of 7 orofacial pain symptoms.
      Pain intensity and psychosocial impact were assessed through the Graded Chronic
      Pain Scale, and the help-seeking response was assessed using the 4-item Level of
      Expressed Need (LEN) measure. RESULTS: Current or episodic symptoms of orofacial
      pain were reported by 57.0% of respondents, and 13.2% of this group reported
      symptoms that had lasted for a 6 months (chronic subgroup). In the chronic
      subgroup, toothache was the most common symptom (42.2%) and oral sores the least
      common (7.8%). The mean pain intensity in the chronic pain subgroup was 46.6 (SD
      21.7) with no age or gender differences (P > .05); 88.2% had low disability
      levels and 11.8% had high levels. 81.4% had low LEN scores and 18.6% had high
      scores, with no age/gender differences (P > .05). CONCLUSION: The prevalence of
      current/episodic orofacial pain was relatively high, whereas chronic orofacial
      pain was much less common. Although the intensity of chronic orofacial pain was
      significant, associated psychosocial disability was low, as was the level of
      perceived need for treatment. These findings may be related to more effective
      pain-coping strategies and greater acceptance of pain in this ethnic group
      compared to other ethnic groups.

PMID- 19090406
TI  - Extraction of RDC/TMD subscales from the symptom check list-90: does context
      alter respondent behavior?
AB  - AIMS: To test whether extraction of the 2 subscales in the Research Diagnostic
      Criteria for Temporomandibular Disorders (RDC/TMD) affected the subscale score
      reliability and whether scores from the RDC/TMD subscales are comparable to the
      same scales when the whole Symptom Check List-90 (SCL-90R) is administered.
      METHODS: The full SCL90-R and a modified version containing only the depression
      and somatization scales were administered in counterbalanced order to 103
      subjects. As another test of context, a subset of participants completed the
      modified and full versions as part of a larger battery of instruments relevant to
      facial pain. Statistical analyses included internal reliability for item analysis
      and intraclass correlation (ICC) and Lin's concordance correlation coefficient
      (CCC) for total scale score reliability. RESULTS: Internal reliability was
      approximately 0.95 for depression and 0.87 for somatization, independent of test
      form. Total scale scores were reliable across test versions, with both ICC and
      CCC approximately 0.95 for depression and 0.91 for somatization. Permutation
      tests using the CCC indicated a mild influence on the somatization score but not
      the depression score due to order effects, but these effects were not significant
      when considering the 95% CIs based on resampling methods. CONCLUSION: Whether
      items from other subscales are present or not does not affect the internal
      reliability or parallel forms reliability of the total scores from either
      depression or somatization. Context of administration, via order of forms
      completion, does not alter total score or reliability of depressive items but may
      alter total scores for somatization.

PMID- 19090407
TI  - Nerve growth factor-evoked masseter muscle sensitization and perturbation of jaw
      motor function in healthy women.
AB  - AIM: To replicate and extend previous findings of nerve growth factor (NGF)
      induced mechanical sensitization in healthy young men to women and test for
      associations between mechanical sensitization and oral motor function. Combined
      these data would indicate if injection of NGF into the masseter muscle is a valid
      model of muscle pain related to temporomandibular disorders (TMD). METHODS: A
      double-blind, placebo-controlled study was conducted on 14 healthy women. Each
      subject received an injection of NGF (5 microg in 0.2 mL) into 1 masseter muscle
      and buffered isotonic saline (control, 0.2 mL) into the other. Pressure pain
      thresholds (PPT) and pressure pain tolerance (PPTOL) as well as self-assessed
      pain intensity (numeric rating scale of 1 to 10) with the jaw at rest and in
      relation to various motor activities (chewing, yawning, talking, swallowing,
      drinking, and smiling) were recorded prior to and 3 hours, 1 day, 7 days, 14
      days, and 21 days postinjection. ANOVAs were used to test data. RESULTS: It was
      found that NGF significantly reduced PPT and PPTOL 3 hours, 1 and 7 days
      postinjection (P < .001). Numerical rating scale (NRS) scores during chewing and
      yawning were significantly increased 3 hours and 1 day following NGF injection (P
      < .001). After 3 hours, there were significant correlations between relative
      changes in PPTs and NRS scores during chewing (r = -0.556; P = .037), between
      relative changes in PPTOL and NRS scores during yawning (r = -0.607; P = .020),
      and between relative changes in PPTOL and maximum unassisted jaw-opening capacity
      (r = 0.868; P < .001). CONCLUSION: This study shows that injection of NGF into
      the masseter muscle of women causes local signs of mechanical allodynia and
      hyperalgesia that persist for at least 7 days as well as pain during strenuous
      jaw movement. Taking the authors' previous results on NGF effects in men into
      consideration, these findings lend additional support to the suggestion that this
      model may serve as a proxy of some of the clinical features of TMD-related muscle
      pain.

PMID- 19090408
TI  - Nonspecific chronic orofacial pain: studying patient experiences and perspectives
      with a qualitative approach.
AB  - AIMS: To analyze the nonspecific chronic orofacial pain patient's experience of
      the pain condition and to gain knowledge on the complexity of the problem.
      METHODS: Fourteen patients (11 female, 3 male) aged 21 to 77 years were selected
      among those referred to a specialist clinic. All selected patients agreed to
      participate. Data were obtained through thematic in-depth interviews that exposed
      the context of the orofacial pain condition. The 2 interviews with each patient
      were audiotaped and transcribed verbatim. The text material was analyzed using a
      qualitative research strategy based on phenomenology. RESULTS: The essence of the
      chronic orofacial pain was expressed by the patients as something that eludes
      perception and comprehension. The pain was difficult to grasp and to communicate.
      The consequence of the pain was experienced by the patients as to be stricken by
      the pain and was expressed as living a life permeated by hopelessness,
      resignation, and a lack of faith. CONCLUSION: The patients in this study
      experienced their chronic orofacial pain to have no limits and to repressively
      permeate all aspects of their existence: social, practical, and emotional.

PMID- 19090409
TI  - Reeves decision changes expert witness qualifications.

PMID- 19090410
TI  - [Doctors and medical practice in France: 1967-1977-2007].
AB  - On the basis of 3 surveys conducted among French physicians in 1967, 1977 and
      2007, the study aims at identifying the current state and the developments during
      the recent decades of certain aspects related to medical practice: distribution
      of physicians according to the place of work, their weekly working time, the time
      they devote to medical readings, the means they utilize for continuing education.
      In 2007, out of 100 active physicians, 60 are in private practice, 19 work in
      university hospitals, 23 in other hospitals, 19 in health centers, 6 in the
      expertise societies or the control departments of sickness insurance funds, 17 in
      other medical activities and 11 carry out non-medical activities. Each of these
      figures includes the professionals having other activities elsewhere. These
      physicians in poly-practice are 47 percent of the medical profession nowadays,
      they were 58 percent 3 decades earlier. In other words, mono-practice, or
      exclusive practice, is fastly expanding. The weekly working time of medical
      doctors in 2007 is 47.9 hours, as compared to 37.9 hours in the whole active
      population in France. The working time of female doctors (42.4 hours) is much
      shorter than that of their male colleagues (52.3 hours). However, during the
      period 1977-2007, the salient feature was that physicians reduced sharply their
      time of work, from 52.9 hours to 47.9 hours. The decrease was an affair of men,
      as female doctors have not shortened their own time. Similarly, time shortening
      was mostly an affair of young and middle-aged physicians, whereas their senior
      colleagues have performed only a slight reduction. As a result, in 2007, the
      physicians aged 55 years and over have the longest working time (48.7 hours) as
      compared to the work week of 46 hours of physicians aged under 40. During the
      last 3 decades, the time devoted to medical readings has also decreased: 4.3
      hours a week in 1977, and only 2.9 hours in 2007, a rhythm 3 times faster than
      the reduction of the working time. The time devoted to medical readings was
      equivalent to 8 percent of the working time in 1977 but the ratio decreased to 6
      percent nowadays. However, surprisingly, the medical journals and textbooks
      remain today among the most popular tools quoted by French physicians among the
      means they utilize for their continuing education. The fact does not hide the
      spectacular expansion of the medical congresses which were less frequently quoted
      in the past, and the brutal emergence of internet on the stage of medical
      continuing education.

PMID- 19090411
TI  - The impact of aging on human sexual activity and sexual desire.
AB  - This article empirically studies how much aging modifies human sexual activity
      and sexual desire, and what the most important determinants in this change are.
      The analyses are based on 2 representative national sex surveys conducted in
      Finland in the 1990s. As a result of female widowhood, aging men had a higher
      incidence of sexual intercourse compared with aging women; and in relationships,
      women were more likely than men to report lack of sexual desire. In regression
      analysis, age was a predictor of sexual activity but not of sexual desire, when
      controlling for the impact of other factors. Relationship duration did not play
      an important role in sexual activity or sexual desire when controlling for a
      number of other variables. Sexual desire, valuing sexuality, and a healthy
      partner were important to female sexual activity; and high sexual self-esteem,
      good health, and active sexual history were important to male sexual activity. To
      keep up their sexual desire, both men and women needed good health, good sexual
      functioning, positive sexual self-esteem, and a sexually skilful partner.

PMID- 19090412
TI  - Perceptions of service user and carer involvement in healthcare education and
      impact on students' knowledge and practice: a literature review.
AB  - BACKGROUND: The involvement of service users in healthcare education has followed
      an increasing focus on patient-centred services. CETL4HealthNE, regional
      healthcare education collaboration, undertook a literature review to inform
      involvement strategies. OBJECTIVES: To identify--approaches used to involve
      service users in healthcare education curricula; perceptions of key stakeholders;
      impact of involvement on students' knowledge and skills, and the quality of care
      delivered. METHOD: A structured search of the literature on service user
      involvement in Higher Education healthcare curricular activity was undertaken
      (July 2006-February 2007). Papers were screened and data extracted and
      synthesized according to the aspect of the curriculum enhanced by involvement and
      level of impact evaluation. RESULTS: Thirty papers addressed interventions in pre
      and 11 in post-registration education. Thirty studies reported on evaluation.
      Students and service users both benefited from service user involvement in health
      care programmes. There was limited evidence that involvement changed behaviour in
      practice or significantly benefited the recipient of care. CONCLUSIONS: Service
      user involvement in curricular developments for healthcare professionals is a
      policy imperative aimed at improving their experience of services. Despite a
      limited and weak traditional evidence base for impact on students' knowledge and
      practice, both students and service users identify benefits from engagement.
      Further development of evaluation methodologies is required.

PMID- 19090413
TI  - Psychiatric symptoms in a patient with Wolfram syndrome caused by a combination
      of thalamic deficit and endocrinological pathologies.
AB  - DIDMOAD or Wolfram syndrome is a hereditary disorder characterized by early onset
      diabetes and optic atrophy. Besides these features, a variety of other symptoms
      have been described including psychiatrical abnormalities leading to
      hospitalization in about 25% of all patients. To our knowledge, until now, a
      detailed characterization of these psychiatric symptoms does not exist. Here we
      describe a 21-year-old male patient with deficits of frontal lobe function, such
      as impaired impulse control and learning deficits. Magnetic resonance imaging
      (MRI) of the brain showed a bilateral optic atrophy, but no signs of frontal
      brain atrophy. Neuropsychological tests revealed performance deficits in complex
      planning (e.g., Tower of London). Also his capacities in memorizing logically
      connected information after a short and delayed period of time were significantly
      reduced. Since histopathological studies did not reveal frontal brain
      abnormalities, but did show thalamic neuronal loss and gliosis, we interpret our
      findings as representative of thalamic dysfunction. In addition, hypoglycaemia
      seemed to trigger rapid mood swings. As soon as blood glucose levels improved,
      the patient stabilized emotionally and assaultive behaviour disappeared while the
      cognitive deficits remained unchanged.

PMID- 19090414
TI  - A case study of long-term cognitive and social functioning following a right
      temporal lobectomy in infancy.
AB  - We present the rare case of an adult patient, FS, who had a right anterior
      temporal lobe resection during infancy to treat intractable epilepsy, and
      underwent a cognitive evaluation 19 years later. Given the paucity of literature
      on long-term outcomes for infants who receive neurosurgery for epilepsy, this
      case provides valuable information for both clinicians and patients. What little
      literature exists on infant and child surgical outcomes for epilepsy suggests a
      variable course, with several areas of possible cognitive and social difficulty.
      FS's assessment at the age of 21 revealed only mild difficulties with memory,
      sequencing, and visual imagery, and spared intellectual functioning, working
      memory, problem-solving and social cognition, along with a high level of
      socioeconomic functioning. Thus, the case of FS suggests that neurosurgery during
      infancy is not necessarily associated with large-scale cognitive impairment, and
      furthermore, that high levels of functioning both educationally and vocationally
      are possible after surgical treatment of epilepsy in infancy.

PMID- 19090416
TI  - H2O2 determination by a biosensor based on hemoglobin.
AB  - The detection of hydrogen peroxide, H2O2, plays an important role in many fields
      including industry, environmental protection, and clinical control. Hydrogen
      peroxide can be toxic if ingested, inhaled, or by contact with the skin or eyes.
      Hemoglobin is a molecule with four electroactive iron hemes which can be used as
      an ideal model molecule for the study of electron transfer reactions of heme
      proteins and also for biosensing and electrocatalysis. The present study
      describes the immobilization of hemoglobin on a Clark electrode surface to
      develop a novel electrochemical biosensor for the detection of hydrogen peroxide.
      The principle of the measurements was based on the electrocatalytic activity of
      the immobilized hemoglobin to the reduction of hydrogen peroxide. Hemoglobin was
      crosslinked with gelatine using glutaraldehyde and fixed on a pretreated teflon
      membrane. The optimum conditions for the biosensor were established. The most
      suitable hemoglobin and gelatin amounts and glutaraldehyde ratio were determined.
      Characterization studies of the biosensor, such as optimum pH and optimum
      temperature, were carried out. The repeatability experiments were done and the
      average value (x), standard deviation (S.D.), and variation coefficient (C.V.)
      were calculated. After the optimization and characterization studies the proposed
      biosensor was applied to determination of H2O2 in real samples.

PMID- 19090415
TI  - Impairment of recollection but not familiarity in a case of developmental
      amnesia.
AB  - In a re-examination of the recognition memory of Jon, a young adult with
      developmental amnesia due to perinatal hippocampal damage, we used a test
      procedure that provides estimates of the separate contributions to recognition of
      recollection and familiarity. Comparison between Jon and his controls revealed
      that, whereas he was unimpaired in the familiarity process, he showed abnormally
      low levels of recollection, supporting the view that the hippocampus mediates the
      latter process selectively.

PMID- 19090417
TI  - Pseudomonas putida based amperometric biosensors for 2,4-D detection.
AB  - Amperometric biosensors using Pseudomonas putida cells as a bioelement were
      developed for 2,4-dichloro phenoxy acetic acid (2,4-D). After the adaptation
      process of Pseudomonas putida to 2,4-D, cells were immobilized onto the screen
      printed graphite electrodes (SPG) as well as Clark oxygen probe by gelatin and
      glutaraldehyde. Optimum pH, temperature, and stability of the biosensor were
      investigated. Substrate specificities for various phenolic compounds were also
      searched. In repeatability studies, variation coefficients and standard
      deviations for both type of systems were calculated; SPG and Clark electrodes
      were calculated and results are given as a comparison of two systems. Finally,
      the biosensors were applied to 2,4-D determination in a real herbicide sample.

PMID- 19090418
TI  - Iron oxide nanoparticle assisted purification and mass spectrometry based
      proteolytic mapping of intact CD4+ T cells from human blood.
AB  - Iron oxide nanoparticles have been used for many years as clinical applications.
      We have developed a rapid immunoaffinity isolation method of CD4+T cells from a
      mixed cell population of human blood using iron oxide nanoparticles. Anti CD4
      antibody has been attached to iron oxide nanoparticles after its surface
      modification. The antibody tagged iron oxide nanoparticle beads are simply
      incubated with the mixed cell population of human blood and CD4+T cells are
      purified using an external magnetic field. The purification level was checked by
      fluorescence microscopy and flow cytometry. The purified CD4+T cells were
      digested with trypsin with different time periods and the products were analyzed
      by MALDI-TOF mass spectrometry, without further fractionation or purification, to
      obtain its proteome pattern. A database search showed a number of peptide masses
      matched specific to T-cell peptide masses. These results indicate that iron oxide
      nanoparticles are useful for CD4+T cell purification, and mass spectrometry based
      proteolytic fingerprint is simple and swift for identifying putative surface
      biomarkers from the whole cell surfaces.

PMID- 19090419
TI  - Pyranose 2-oxidase (P2O): production from trametes versicolor in stirred tank
      reactor and its partial characterization.
AB  - Optimization of pyranose-2-oxidase (P2O) production conditions from Trametes
      versicolor was carried out in shaking cultures containing glucose, malt, and
      yeast extracts; the optimum concentration values were found to be 1.5% glucose,
      1.0% yeast extract, and 1.0% malt extract, pH 5.0, temperature, 26 degrees C, and
      agitation rate 150 rpm. For the first time, P2O production was also carried out
      in a stirred tank reactor (STR) with 2.2 L working volume in the optimized medium
      composition, and biomass, P2O activity, protein, nitrogen and glucose
      concentrations were also monitored besides pH and dissolved oxygen (DO). In the
      STR, P2O activity peaked on day 9. Partial enzyme characterization occurred and
      optimum pH and temperature were detected as 7.0 and 37 degrees C, respectively.
      K(m) value was found to be 1.009 mM.

PMID- 19090420
TI  - Isolation and identification of alpha,alpha-trehalose and glycerol from an arctic
      psychrotolerant Streptomyces sp. SB9 and their possible role in the strain's
      survival.
AB  - Streptomyces sp. strain SB9 was isolated from perm frost soil samples in
      Spitsbergen, Arctic Ocean; it grows in a temperature range between 4 degrees C
      and 28 degrees C. During the survey of biologically active metabolites
      biosynthesized by this strain, significant amounts of alpha,alpha-trehalose (1)
      and glycerol (2) were detected. The compounds were isolated from the mycelium,
      were chromatographically separated, and the structures were elucidated on the
      basis of MS and NMR measurements. A possible role of trehalose in cold adaptation
      of the strain was examined. It was determined that the mycelium of the strain
      cultivated at 4 degrees C accumulated 5-fold higher amounts of trehalose in
      comparison with the cells cultivated at 28 degrees C. The mesofilic reference
      strains, Streptomyces spectabilis NRRL 2494 and Streptomyces lividans TK64,
      accumulated 100-fold less trahalose than the psychrotolerant Streptomyces sp.
      SB9. High amounts of trehalose in the cells could be a reason for adaptation of
      the strain to life at Arctic conditions.

PMID- 19090421
TI  - Purification and characterization of a new dimeric mannose/glucose-binding
      isolectin from Vicia tetrasperma (L.) Schreber.
AB  - A new mannose/glucose specific isolectin VTL-II has been purified to
      electrophoretic homogeneity from the seeds of Vicia tetrasperma (L.) Schreber
      through successive steps of (i) lectin extraction, (ii) ammonium sulfate
      fractionation (30-50%), and (iii) affinity chromatography on a column of Sephadex
      G-50 covalently coupled with D-mannose. The isolectin was found to be a dimeric
      protein of molecular weight 62 kDa made up of apparently chemically identical
      subunits unlike the tetrameric isolectins reported earlier from the same plant
      source. It was found to exhibit (i) 8-16 times higher specificity for rabbit RBC
      than human RBC, though it showed unspecificity with respect to the different
      human blood groups, (ii) non-dependence on divalent metal ion for its
      hemagglutinating activity, (iii) relatively broad pH optimum ranging from pH 7.0
      to 8.0, and (iv) thermal inactivation behavior characterized by t(1/2) of 50
      degrees C.

PMID- 19090422
TI  - DNA isolation and amplification from formaldehyde-fixed animal tissues rich in
      mucopolysaccharides, pigments, and chitin.
AB  - Formaldehyde, once the fixative of choice, is a known obstacle to DNA extraction
      and amplification. However, when fixed tissues contain other problematic
      compounds such as pigments, mucopolysaccharides, and chitin, and when only small
      amounts of archival tissues are available, obtaining amplifiable DNA can become
      extremely challenging. Here, I present a procedure that has enabled me to extract
      amplifiable DNA from minute specimens of polychaetes successfully; like many
      other invertebrates, these worms are rich in pigments, mucopolysaccharides, and
      chitin. This inexpensive procedure can be used to obtain and amplify DNA from
      miniscule amounts of other similarly-problematic formaldehyde-fixed tissues as
      well.

PMID- 19090423
TI  - Evaluation of the potential cytotoxicity of metals associated with implanted
      biomaterials (I).
AB  - The present assessments of potential toxicity of metal ions (Al, Ni, Cr, V, and
      Ag) that construct the metallic biomaterials were carried out in vitro. By
      measurements of cell alkaline phosphatase (ALP) activity and reduction ability of
      cell methyl tetrazolium (MTT), the cytotoxicity of prevalence metallic
      biomaterials has been investigated. Furthermore, the poison and erosion of metal
      ions and atoms on human tissue are discussed. Research results indicated that
      trace Cr(VI) showed serious cytotoxicity and Ni as well as V are cytotoxic if the
      ion concentration in culture medium is over 100 micromol x L(-1) and 1 micromol x
      L(-1), respectively. A strange phenomenon is that Ag also is cytotoxic if the ion
      concentration is higher than 500 micromol x L(-1). Al ion is biphasic in
      cytotoxicity. At low ion concentration (< 10 micromol x L(-1)), Al ions can
      stimulate cell proliferation, whereas at concentrations over 1,000 micromol x L(
      1), cytotoxicity increases.

PMID- 19090425
TI  - [Pediatric surgery in a general hospital--pros and cons].

PMID- 19090426
TI  - [The future of children's hospitals--demographic trends of children aged 0 to 15
      in Germany up to 2050].
AB  - The 11th coordinated population forecast of the German Federal Statistical Office
      shows that the number of children in the age group 0-15 is going to decrease
      considerably up to 2050. Depending on the assumptions, the number of children
      will decrease to 50-80% of today's level. There are only small regional
      differences in this development, i. e., all regions will be equally affected by
      the population decline. However, large cities and surrounding areas will face
      smaller reductions than other community types. The timing of the decline differs
      somewhat between the regions. An exception is the age group 10-15 in East
      Germany. After a strong reduction of births in the years after the reunification,
      birth rates have been rising since 1998, which will lead to a relative increase
      of that age group in the coming years. However, also in this age group, the
      number of children is going to decrease to 85% of today's level up to 2050. In
      parallel to the reductions in the young population, there will be a reduction in
      the frequency of diagnoses, whereby in a simplified "status quo" model, the
      amount of diagnoses will decrease in proportion to the number of the 0-15-year
      olds.

PMID- 19090427
TI  - [Inguinal hernia, and hydrocele--special features in infants and children].
AB  - Inguinal hernia, undescended testicle and hydrocele are typical and frequent
      diseases in infants and children. The paediatric inguinal hernia is a congenital
      defect and the hernial sac usually passes the inguinal canal. In order to
      diagnose the inguinal hernia in infants the physician is frequently dependent on
      the accurate observation of the parents. Although laparoscopic herniotomia is
      increasingly being discussed, it cannot be recommended yet as a standard
      operation because of a recurrence rate of 4%. Undescended testicle is classified
      into several subtypes with specific diagnostics and therapies. The role of
      hormonal therapy is currently controversial again, but the literature seems to
      point to a positive role for fertility in adulthood. The appropriate therapy
      should be performed by the end of the first year of life. A hydrocele is no acute
      reason for operative therapy; normally one can wait until the 2nd-4th year of
      life for spontaneous regression except for very large forms.

PMID- 19090428
TI  - [Minimally invasive paediatric surgery in other than paediatric surgical
      departments].
AB  - Minimally invasive techniques are well established in numerous paediatric
      surgical departments. They are safely applied to children of all age groups.
      Numerous types of procedures have been established specifically for children and,
      therefore, the necessary expertise cannot be derived from general surgical
      experience. Advantages in postoperative symptoms, convalescence and cosmesis have
      been confirmed. However, data or recommendations concerning the use outside of
      centres of paediatric surgery are lacking. In the opinion of the authors,
      minimally invasive paediatric surgery should only be considered for departments
      with a volume of paediatric specialty operations similar to that of paediatric
      surgical centres. In addition, an adequate number of operations, specific
      expertise of the surgeons in minimally invasive paediatric surgery, and specific
      expertise of anaesthesiologists is mandatory. Today, these prerequisites can only
      be assumed for non-paediatric specialty operations, such as laparoscopic
      appendectomy. In conclusion, before recommendations can be made for minimally
      invasive techniques in specialty paediatric operations outside of paediatric
      surgical centres, the feasibility and safety under these conditions has to be
      investigated.

PMID- 19090429
TI  - [Anaesthesiological aspects of paediatric medical care in "non-specialised
      departments"].
AB  - Paediatric perioperative care represents specific challenges related to the
      distinct developmental, anatomic and physiological characteristics of children,
      requiring specialised expertise, including pharmacology. A specially trained
      anaesthesia team, an appropriate environment and appropriate paediatric-sized
      equipment (endotracheal tubes, cannulas) represent key factors in determining the
      perioperative outcome for this population. Other important equipment that must be
      adapted to the paediatric population include: Non-invasive anaesthesia monitoring
      equipment (ECG, blood pressure cuff, pulse oximetry, capnography, oxygen monitor,
      volatile gas concentration monitor, peripheral nerve stimulator and temperature
      probe); as well as specialised ventilators that allow pressure- and volume
      controlled ventilation with volumes as low as 20 ml, variable high frequency
      ventilation up to 60 breaths per minute and paediatric ventilator hose systems
      with automatic correction for compliance. Perioperative pain management is
      important in the paediatric population, with regional anaesthesia techniques
      (usually done under general anaesthesia) being increasingly accepted in all age
      groups. These techniques, however, should be performed by experienced
      anaesthesologists and surgeons only. If these conditions are not met, surgical
      procedures should not be performed except in the case of an emergency when
      transportation to a specialised paediatric facility cannot be done safely. This
      is particularly critical for premature babies, newborns, and infants up to 3
      years of age.

PMID- 19090430
TI  - [Special features and possible pitfalls in paediatric trauma care].
AB  - Paediatric trauma care represents treatment of a dynamic and growing system.
      Following evaluation of fracture stability, the individual spontaneous correction
      can be included. Possible pitfalls can occur with diagnosis, indication, choice
      of the treatment modality, surgical technique and follow-up. Treatment in a
      specialised paediatric trauma centre is not always possible and is not necessary
      in all childhood injuries. But the paediatric trauma centres have to set
      standards, to show problems, to investigate alternatives, to present solutions
      and to secure a child-appropriate treatment by competence, communication and
      cooperation with all other care takers.

PMID- 19090431
TI  - [Which paediatric urological procedures can be performed in a general hospital?].
AB  - Principally, surgical procedures in children should be performed in specialized
      pediatric centers. Some minor procedures on older children could eventually take
      place in general hospitals, provided that pediatric medical and nursing
      competence is available. Adequate infrastructure and an environment appropriate
      for children are required as well. The comfort of therapy in an adjacent general
      hospital should not lead to an increased risk for the child. Principles of
      clinical diagnosis and treatment strategies of frequent pediatric urological
      entities are described and discussed in this article.

PMID- 19090432
TI  - [Distinctive features of appendicitis in childhood].
AB  - INTRODUCTION: This article describes the specific features of the diagnostics and
      therapy for acute appendicitis in childhood. As a result of the rapid progression
      of appendicitis in children, in spite of extensive diagnostic possibilities, we
      still see significant rates of perforation or vice versa of the so-called
      negative appendectomies. PATIENTS AND METHODS: Our own results (1,247
      appendectomies) of 20 years (1987-2006) were retrospectively analysed. The
      patients had an average age of 10.3 years (range: 3 months-18 years). RESULTS:
      The perforation rate was approximately 8.5%, the non-positive appendectomy rate
      15.5%. The laparoscopic approach amounted constantly to 20% in the last 5 years.
      The median length of hospitalisation was reduced from 9.1 (1987-1991) to nearly 5
      days (2002-2006). The relevance of active observation by experienced surgeons in
      addition to ultrasonographic examinations of the abdomen is stressed. CONCLUSION:
      The appendectomy in children can be performed either by an open or a laparoscopic
      approach. The expected advantage of the endoscopic procedure (due to the smaller
      trauma of access) could not be proven in our own patients, as well as in various
      prospective studies. The early diagnosis and therapy are still today a challenge
      for the attending doctors.

PMID- 19090433
TI  - [Cooperation model between an university clinic and a peripheral paediatric
      surgical department].
AB  - INTRODUCTION: The lack of young physicians in Germany, who are willing to train
      in surgery, is caused by several factors. Due to the demographic development and
      the specialisation in paediatric surgery in university institutions, attracting
      trained paediatric surgeons became difficult for non-specialised rural paediatric
      surgical departments, which is often also complicated by economic pressures.
      Strategies, such as cooperation between hospitals or departments, are required.
      We present a mid-term analysis of the first paediatric surgical cooperation
      between a university clinic and a rural paediatric surgical department in Lower
      Saxony. METHODS: The Department of Pediatric Surgery, Hannover Medical School
      (MHH), is a university centre with a case load of about 1,700 surgical procedures
      per year with a case mix index (CMI) of 1.3. The Department of Paediatric
      Surgery, St. Bernward Hospital Hildesheim (BK), is a peripheral institution with
      about 1,200 surgical procedures per year and a CMI of 0.5. A cooperation project
      was inaugurated in October, 2004, between the two departments. The aim of the
      cooperation was to support the head of the paediatric surgical department at the
      BK by rotating trained paediatric surgeons from the MHH. Simultaneously, it was
      planned to offer attractive conditions for research at MHH for participating
      surgeons. The cooperation further included sufficient economic cover of 1.5 posts
      for rotating medical staff by the BK. RESULTS: Three trained paediatric surgeons
      have so far been included in the rotation programme between the two cooperating
      paediatric surgical departments. The rotating medical staff costs were covered by
      the BK. Over a period of 2.5 years, MHH surgeons performed about 50 % of all
      surgical procedures at BK, while undertaking two-thirds of on-call duties there.
      Analysis of academic research revealed 3 accomplished experimental and 4 clinical
      studies, as well as 10 published articles. CONCLUSIONS: The paediatric surgical
      cooperation was rated as a success by the rotating trained paediatric surgeons,
      the heads of both departments and the hospital administrations. The academic link
      to a university clinic also increased the attractiveness to work in a paediatric
      surgical department at a rural hospital.

PMID- 19090434
TI  - [The legal bearings of the case medical specialist standard of pediatric surgery
      in the general hospital].

PMID- 19090435
TI  - [Rectal melanoma: the value of modern treatment].
AB  - Rectal melanoma is a rare disease. There is much controversy concerning cause,
      incidence and treatment of the disease and the spreading of recurrence. In this
      article, we discuss actual aspects of diagnostic, therapy and prognosis on the
      basis of our series of seven patients as well as a literature review. The
      surgical therapy in the form of local tumour excision with a disease-free margin
      of up to 1-2 cm is the initial therapeutic modality of choice. Large tumours that
      obviously could not be removed in sano should be treated with a multimodal
      concept. Such tumours should be treated by a combination of neoadjuvant radiation
      and chemotherapy for down-staging with subsequent local excision (LE) or abdomino
      perineal rectum extirpation (APR). An inguinal lymphadenectomy should only be
      performed if the lymph nodes are enlarged on clinical or radiological
      examination. The prognosis of rectal melanoma is markedly poor and is primarily
      related with the stage of disease. The 5-year survival rate is estimated at about
      24% for patients with stage I tumours. Patients with stage II and III tumours
      have appreciably shorter survival times of 12 months on the average.

PMID- 19090436
TI  - [The preoperative multislice spiral CT in the surgical management of pulmonary
      metastases].
AB  - INTRODUCTION: Inspection and palpation of the ventilated and exhausted lung
      reflect the guideline-compliant surgery of pulmonary metastases. Because a huge
      number of pulmonary nodules are missed on preoperative CT, metastases must be
      diagnosed by the surgeon's examination of the lung under exclusion of the video
      assisted approach. The purpose of our study was to assess whether a special
      multislice (MS) spiral CT may close this diagnostic gap and change the management
      of pulmonary surgery. PATIENTS AND METHODS: We performed a prospective study to
      address this question. Operative and histological results of 60 patients with
      pulmonary nodules (7/2002 and 12/2004) were compared with the preoperative
      predictions of MS-CT. RESULTS: In 81 operations, 166 pulmonary metastases were
      confirmed histologically. The MS-CT predicted 229 suspicious metastases; 38%
      could not be confirmed histologically. However, in 14% of surgically confirmed
      metastases the radiological correlate was absent. 44% of these metastases were
      <or=2 mm, 30%<or=4 mm, and 26%>4 mm; and were from the following primary
      entities: 48% hypernephroma, 30% sarcoma, 17% colorectal carcinoma and 4% breast
      cancer. The radiological prediction of 1 to 3 vs. 5 to 11 metastases implied 30%
      vs. 70% additional filiae, whereas radiologically non-described metastases were
      found in 12% of all operations. In contrast, the group with radiopaque material
      showed only 5% of metastases without a radiological correlate or 8% of non
      described metastases. The overall sensitivity of MS-CT was 86%, whereas the group
      with radiopaque material had a sensitivity of 95%. CONCLUSION: The preoperative
      MS-CT does not resolve the problem of overlooked metastases and has no influence
      on the management of pulmonary surgery.

PMID- 19090437
TI  - [Minimal invasive transvaginal right hemicolectomy: report of the first complex
      NOS (natural orifice surgery) bowels operation using a hybrid approach].
AB  - BACKGROUND: Laparoscopic surgery has dramatically changed abdominal surgery by
      reducing the risk of wound infections, incisional hernias and adhesions. The
      surgical concept using natural orifices (NOS) may be even less traumatic and so
      less invasive. PATIENT AND METHODS: This operation was performed in a 66-year-old
      woman with an adenoma in the ascending colon. Through a 5 mm incision at the
      umbilicus a pneumoperitoneum was created and a trocar inserted. For the operation
      a 12 mm trocar and a curved grasper have been inserted in the posterior fornix of
      the vagina. Because of adhesions an additional 5 mm trocar was necessary. Through
      this incision the laparoscopic right hemicolectomy with an intracorporal
      anastomosis was performed. RESULTS: The histology showed an adenoma with 21 lymph
      nodes. The removal of the specimen through the vagina was without any
      difficulties. The postoperative course was regular. CONCLUSIONS: This operation
      is to our knowledge the first right hemicolectomy as a NOS/NOTES-operation in a
      human patient. It shows that with rigid instruments even complex procedures
      through natural orifices are feasible.

PMID- 19090438
TI  - [Filling of metaphyseal defects with nanocrystalline hydroxyapatite (Ostim) for
      fractures of the radius].
AB  - AIM OF THE STUDY: In this study, innovative bone replacement material was tested
      after complicated metaphyseal radius fractures with the affected joints. MATERIAL
      AND METHODS: In all, 11 C 2, 11 C 3 and 3 A 3 radius fractures were treated by
      surgery combining an angularly stable palmar plate osteosynthesis with defect
      filling using nanocrystalline hydroxyapatite. Examinations were conducted
      preoperatively and postoperatively after 4 weeks, 12 weeks and 9-12 months.
      RESULTS: After 10.5+/-1.4 months, inclination angles of 8.7+/-1.8 degrees
      (dorsopalmar) and 18.8+/-2.9 degrees (radioulnar) were measured at the treated
      fractures, the ulnar drift was 0.6+/-1.8 mm. According to the Gartland/Werley
      scale, 10 therapeutic results were considered "excellent", 12 "good" and 3
      "fair". CONCLUSION: An angularly stable plate osteosynthesis with metaphyseal
      defect filling using nanocrystalline hydroxyapatite for the treatment of A 3, C 2
      and C 3 radius fractures showed satisfactory radiological and clinical results.

PMID- 19090439
TI  - [Elective lymph node dissections--still a standard in cancer surgery?].
AB  - PURPOSE: Since more than a century elective radical dissection of regional lymph
      nodes is a standard procedure in tumour surgery. We discuss whether or not this
      standard is still up to date. METHODS: The discussion was based on evaluations
      from well known clinical trials and cohort studies as well as from the results of
      the Munich Cancer Registry (MCR). RESULTS: Distant metastases develop
      extravasally from disseminated tumour cells that originate from the primary
      tumour. Therefore, three categories of metastases can be described: First,
      regional lymph node metastases treated by surgical and/or adjuvant therapy or by
      watchful waiting. Although the number of positive lymph nodes is one of the most
      important prognostic factor in all cancer sites, treatment of lymph nodes does
      not affect long-term survival. The number of positive lymph nodes is therefore
      simply a marker, but not a cause, of distant metastases. This seems to be
      generally valid. Also, the major part of local recurrences can be seen as "local
      metastases". The frequency of local relapse can be influenced by surgery,
      adjuvant treatment or radiotherapy only with a small impact on survival. Distant
      metastases normally determine the course of disease. Whether metastases can be a
      source of new clinically relevant metastases that influence the prognosis has to
      be questioned by the presented analyses of tumour growth times. CONCLUSIONS: The
      gene-based control of metastases implies a principal process of metastatic spread
      for solid tumours. The hypothesis "metastases do not metastasise" has a high
      plausibility. Reduction of lymph node dissection and its performance only in
      those cases where it is necessary for treatment decisions seems to be (bio)
      logically consequent.

PMID- 19090440
TI  - [Implantation of bipolar prosthesis for treatment of medial femoral neck
      fractures in the elderly--clinical and radiographic outcome].
AB  - In our study, we retrospectively evaluated 203 patients with medial or lateral
      femoral neck fractures who received 210 bipolar prosthesis (7 bilateral
      implantations) at our institution. 204 patients underwent cemented bipolar
      hemiarthroplasty. These included 149 females and 54 males with a median age of 82
      (46-97) years. At the time of surgery 144 patients (71%) suffered from more than
      3 medical conditions. We conducted our follow-up examination at a median of 27.9
      months after the operation, at which time 97 patients (48%) had already died. On
      examination, 17% of our 76 patients had a Harris hip score between 90 and 100 and
      20% between 80 and 89 or 70 and 79, respectively. 43% had a score of less than
      70. In 20 patients (57%) we found radiographic evidence of periarticular
      ossification. Signs of loosening according to Gruen were found in 7 out of 35
      patients, with no apparent clinical correlation. Surgery-related complications
      were noted in 15% of our 203 patients--mostly, with 10 cases each, wound
      infections and postoperative haematomas. In 3 cases of deep wound infection, a
      removal of the prosthesis was necessary, leading to a Girdlestone hip in one
      case. Postoperative hip dislocations occurred in 3.4% and intraoperative femur
      fissures were encountered in 1% of our patients. There were no cases of nerve
      damage or protrusion of the acetabulum reported. 43% of our patients developed a
      general complication--mainly cardiological or vascular problems, nephrological or
      urinary tract diseases, pulmonary or neurological complications. Hip arthroplasty
      is predominantly applied in older patients, most of them suffering from at least
      one medical condition at the time of surgery that influences their hospital
      course. This is why especially the overall physical condition of elderly patients
      has to be taken seriously into account when planning surgical treatment of
      femoral neck fractures. In our retrospective study, we have shown that
      implantation of a bipolar hip prosthesis constitutes an adequate treatment for
      these patients.

PMID- 19090441
TI  - [Clinical accuracy of fluoroscopic navigation at the thoracic and lumbar spine].
AB  - The aim of the present study was the verification of the accuracy of 2D
      fluoroscopy-based navigated pedicle screw placements at the thoracic and lumbar
      spine in a case series of traumatised patients. Within 36 months 111 pedicle
      screws were instrumented using C-arm based navigation in 29 patients, 60 at the
      thoracic and 51 at the lumbar spine. All screw positions were evaluated
      postoperatively by a routine thin-slice CT scan using multiplanar reconstruction.
      The position of a screw in relation of its pedicle was classified as: a) screw
      completely intraosseous, b) screw perforated less than thread level and c) screw
      perforated over thread level. In 34 thoracic (56.7%) and 32 lumbar (62.7%) screws
      complete intraosseous placement was observed, 14 thoracic screws (23.3%) and 14
      lumbar screws (27.5%) perforated less than thread level. Perforations over thread
      level were found in 12 thoracic (20%) and 5 lumbar (9.8%) screws. Only medial and
      lateral perforations of the pedicle were documented (without neurological signs),
      cranial or caudal perforations did not occur. Segmentation of the C-arm
      navigation into two comparable treatment periods showed a learning curve with a
      reduction of perforations in the second sequence (after 57 pedicle
      instrumentations) of about 15%, this was not found to be statistically
      significant. The fluoroscopic navigation of pedicle screws is a safe procedure at
      the lumbar spine with equal accuracy compared to the non-navigated conventional
      instrumentation. Application of C-arm navigation at the thoracic spine showed
      more inaccuracies, so that 3D-based navigation seems to be more advantageous in
      this region.

PMID- 19090442
TI  - [No influence of physiotherapy on outcome after open repair of achilles tendon
      ruptures?].
AB  - AIM: Many studies have been performed to analyse the influence of surgical
      techniques and the postoperative aftercare after Achilles tendon ruptures on the
      outcome. However, there is no study investigating the influence of physiotherapy
      on outcome after surgical repair and standardised early functional rehabilitation
      of Achilles tendon rupture, so that this was the objective of the present study.
      PATIENTS AND METHODS: In this retrospective study, 104 patients with Achilles
      tendon ruptures, all treated by open repair followed by a standardised early
      rehabilitation, were evaluated by the Thermann score. The average age was 42
      years. We could identify 3 patient groups. Group I (n=23) did not receive any
      physiotherapy. Group II (n=41) received physiotherapy for 3-6 weeks, and group
      III (n=40) received more than 6 weeks of physiotherapy. Physiotherapy consisted
      of 3 units per week. Each unit lasted for 30 min. All groups were compared
      statistically via variance analysis. RESULTS: Group I scored on average 88.8
      points, group II 88.6 and group III 87.0 points. There were no statistically
      significant differences between the three groups (p=0.50). The age of patients
      had also no relevant influence on the outcome (p=0.48). CONCLUSIONS:
      Physiotherapy and age of the patients involved were not found to influence the
      outcome after open augmented repair of Achilles tendon ruptures followed by a
      standardised early rehabilitation. These results should be confirmed by a
      prospective randomised trial. Also elderly patients participating in demanding
      sport activities should receive a surgical repair.

PMID- 19090443
TI  - [PCO syndrome--is it an indication for bariatric surgery?].
AB  - BACKGROUND: The polycystic ovary syndrome (PCOS) is the most frequent cause of
      female infertility with an estimated prevalence of 6-10% in premenopausal women.
      Due to its long-term metabolic and cardiovascular consequences, it poses a severe
      health problem. Visceral obesity and subsequent insulin resistance represent the
      core pathophysiology of PCOS, clearly suggesting that measures to reduce
      abdominal obesity should be pursued. METHODS: Between February 1995 and October
      2006, 204 patients underwent bariatric surgery in the SRH Hospital of Gera. 75%
      of the patients were female and three of them were suffering preoperatively from
      polycystic ovary syndrome and metabolic syndrome. RESULTS: 104 months after
      laparoscopic adjustable gastric banding, the excess body weight loss (EBWL) was
      49, 67 and 41% in these three patients, respectively. Glucose levels normalised
      completely. One patient became pregnant after weight reduction. CONCLUSIONS: In
      PCOS with metabolic syndrome, bariatric surgery is an option to reduce weight and
      to treat associated metabolic disorders. Surgery should be performed based on the
      body mass index, the metabolic disorders, and the wish of the patient to become
      pregnant.

PMID- 19090444
TI  - [The tumor stem cell and the carcinogenesis].

PMID- 19090446
TI  - [Selective primary obesity prevention in children].
AB  - BACKGROUND AND OBJECTIVE: Obesity in children is characterized by a rapid gain of
      weight starting at an age of 4 to 5 years. We investigated whether low threshold
      prevention prevented a further increase of the Standard-Deviation-Score of the
      BMI (BMI SDS) in children with impending obesity. PATIENTS AND METHODS: The
      network CrescNet collected data from more than 300,000 children. We selected 365
      children with impending obesity (age 4 to 7 years). After randomisation the study
      population was divided into an intervention group (180 children) and a control
      group (185 not informed children). The paediatrician carried out a low threshold
      intervention consisted of an age-adapted nutrition and exercise program to
      inspire the awareness of the adequate nourishment and motion. RESULTS: 59
      children of the intervention group opted for a participation and 49 of them took
      part to the end of the study. This study population stabilized their BMI SDS (p <
      0.025). The children randomised in the intervention group who were not interested
      to participate, and the children of the control group increased their BMI SDS
      within the observation period of one year (p < 0.001, p = 0.002). According to
      nutrition diaries a decrease energy intake of the participants of the
      intervention group was detected. The percentage of protein intake was
      particularly remarkable, amounting to 363 % fulfillment of demand at the
      beginning of the study and 274 % at the end. A regression analysis suggests that
      an intervention and also the approval to take part in the study had a significant
      influence on changes in BMI SDS. CONCLUSION: A low threshold intervention in
      early childhood could successfully prevent an increase of obesity.

PMID- 19090447
TI  - [Rare neuroendocrine carcinoma of the gall bladder. Coincidental occurrence of an
      endometrioid ovarian adenocarcinoma].
AB  - HISTORY AND CLINICAL FINDINGS: The histological investigation of a surgical
      specimen (after cholecystectomy) from a 73-year-old woman revealed a poorly
      differentiated carcinoma with glandular structures and a lymph node metastasis.
      INVESTIGATIONS: Comparative immunochemistry, done to exclude metastatic growth of
      the previously demonstrated endometrioid ovarian carcinoma, was (1) negative for
      CK7 and CA125, positive for CK20, chromogranin A and synaptophysin (gall bladder
      and lymph node metastasis); (2) positive for CK7 and CA125, negative for CK20,
      chromogranin A and synaptophysin (ovary). DIAGNOSIS: The tumor lesion within the
      gall bladder and lymph node was classified as a neuroendocrine carcinoma, not a
      metastasis of the ovarian carcinoma. TREATMENT AND CLINICAL COURSE: The patient
      underwent another laparotomy with resection of the stump of the cystic duct and
      the liver parenchyma surrounding the former gall bladder, including dissection of
      the lymph nodes within the hepatoduodenal ligament. After 14 months another
      metastasis of the neuroendocrine carcinoma of the gall bladder was found. But for
      eight years there has been no recurrence of the endometrioid adenocarcinoma of
      the left ovary. CONCLUSION: Because of the increasing incidence of malignant
      diseases and second neoplasms there is a growing need for such diagnostic tests
      as histological and immunohistochemical analysis. This is the first case,
      according to the available literature, of an endometrioid adenocarcinoma of the
      ovary concomitant with a neuroendocrine carcinoma of the gall bladder.

PMID- 19090448
TI  - [Reversible complete heart block by re-infection with Borrelia burgdorferi with
      negative IgM-antibodies].
AB  - PAST HISTORY AND PHYSICAL EXAMINATION: A 38-year-old farmer presented at his
      general practitioner with dizziness. Physical examination was notable for a heart
      rate of 35 beats/min. The electrocardiogram (ECG) showed a complete (third
      degree) heart block with a bradycardic ventricular escape rhythm. The patient
      reported having had an rash on his right lower leg six weeks previously. After
      spreading centrifugally it had turned pale in its centre, then regressed and
      finally disappeared. After having been supplied with a temporary pacemaker in a
      county hospital the patient was transferred to our hospital. ADMISSION FINDINGS:
      The ECG showed pacemaker stimulation of the ventricle at about 60 beats/min.
      Without this stimulation the complete atrioventricular block persisted. Coronary
      heart disease was excluded by angiography and levocardiography revealed normal
      systolic left ventricular function. Serological findings were a positive titre of
      IgG-antibodies against Borrelia while the IgM titre was negative. THERAPY AND
      COURSE: The heart block disappeared under antibiotic therapy with ceftriaxon
      within eight days, after first changing to transitory second and first-degree
      atrioventricular block, and the pacemaker was removed. The patient did not
      develop any neurological symptoms. CONCLUSION: Cardiac involvement in Lyme
      disease can be the only manifestation of borreliosis. Possible reversibility
      under antibiotic therapy is an important aspect of diagnosis. In spite of
      atypical serology the combination of history, symptoms and serological findings
      will lead to the diagnosis Lyme disease.

PMID- 19090449
TI  - [26-year-old woman with strong, partly crampy pains in upper abdomen].

PMID- 19090450
TI  - [Monitoring of basic functions in intensive care: benefits and risks].

PMID- 19090451
TI  - [Cathelicidins: multifunctional defense molecules of the skin].
AB  - The human skin is constantly exposed to microbial pathogens but infections only
      rarely occur. Innate cutaneous immunity is a primary system for protection
      against infection, and antimicrobial peptides (AMPs) expressed in skin are
      essential defence molecules. The AMPs include molecules such as the defensins
      that were first characterized for their antimicrobial properties as well as other
      peptides and proteins first known for their activity as chemokines, enzymes,
      enzyme inhibitors and neuropeptides. Cathelicidins are unique AMPs that act as
      defensive and signalling molecules. Two different pathways are involved in this
      function: cathelicidins have direct antimicrobial activity and they also initiate
      a host of cellular responses in cytokine release, inflammation and angiogenesis.
      Several skin diseases are associated with cathelicidin dysfunction. In atopic
      eczema, for example, cathelicidin expression is suppressed, whereas in rosacea
      cathelicidin peptides are abnormally processed to forms that induce cutaneous
      inflammation and a vascular response. In psoriasis cathelicidin peptide converts
      self-DNA to a potent stimulus in an autoinflammatory cascade. Current studies
      have unexpectedly identified vitamin D3 as a major factor for the regulation of
      cathelicidin expression. This finding may provide new strategies in the
      management of infectious and inflammatory diseases of the skin by targeting
      control of the expression and function of cathelicidin and other AMPs.

PMID- 19090452
TI  - [MCI-plus: mild cognitive impairment with rapid progression. Part I: prevention
      and therapy].
AB  - Mild Cognitive Impairment (MCI) is a prevalent problem in the elderly and many
      patients show predictors of rapid cognitive decline ("MCI-plus"). MCI-plus
      represents a syndrome with growing importance in an ageing society, which will
      increasingly affect primary medicine and most other clinical specialties. We will
      have to face the dilemma of fast progress in the field of neurodiagnostics with
      innovative therapeutic strategies lagging behind. Psychological and medical co
      morbidity in MCI-plus will therefore offer important opportunities to delay and
      to avoid the manifestation of dementia. We will review and discuss current
      training and treatment options including symptomatic and causal interventions.

PMID- 19090455
TI  - Vasodilator and antioxidant effect of xanthones isolated from Brazilian medicinal
      plants.
AB  - Vasorelaxant and antioxidant activities are important in the therapy for
      cardiovascular diseases. We aimed at investigating the vasorelaxant and
      antioxidant activities of six xanthones isolated from Brazilian medicinal plants.
      Xanthone ( 1), 1-hydroxyxanthone ( 2), 4-hydroxyxanthone ( 3), 1-hydroxy-8
      methoxyxanthone ( 4), 1,3-dihydroxy-7-methoxyxanthone ( 5) and 2,6,8-trihydroxy-1
      methoxyxanthone ( 6) induced concentration-dependent vasorelaxant effects in
      endothelium-intact mice aortic rings. The presence of a hydroxy group in position
      1 seemed to decrease the vasodilator effect while a hydroxy in position 4 and an
      increased number of hydroxy groups improved the vasorelaxatory potential of
      xanthones. All xanthones showed antioxidant activity but their potencies did not
      correlate with the vasodilator effect. Our results suggest that the tested
      xanthones are potentially vasorelaxant and antioxidant compounds but the two
      activities are not interrelated.

PMID- 19090456
TI  - Lobulated colonic lipoma mimicking carcinoma with intermittent intussusception.

PMID- 19090453
TI  - Predischarge morbidities in extremely and very low-birth-weight infants in
      Spanish neonatal units.
AB  - We sought to describe neonatal morbidities and therapeutic interventions in very
      low-birth-weight (VLBW) and extremely low-birth-weight (ELBW) infants cared for
      in Spanish hospitals. We preformed a prospective collection of data covering the
      perinatal period until discharge by the SEN1500 network. This network, set up by
      the Spanish Society of Neonatology, targets VLBW and ELBW infants (400 to 1500 g)
      admitted to neonatal units in Spanish hospitals. Data were recorded in electronic
      form and controlled for possible errors or inconsistencies before analysis. We
      report data for 8836 neonates admitted to 48 neonatal units from January 2002 to
      December 2005. Prenatal steroids were given to significantly more newborns in
      2003 to 2005 (79.4%) than in 2002 (73.4%), although the remaining perinatal data
      examined failed to significantly vary. Delivery was by cesarean section in 69.8%
      of cases but significantly lower (35.9%) for infants under a postmenstrual age of
      26 weeks. Hyaline membrane disease was diagnosed in 53.9% of the newborns and
      bronchopulmonary dysplasia (BPD) in 10.46%. Mechanical ventilation was employed
      in 69.1%, surfactant in 50.3%, and steroids for BPD in 5.3%. Intraventricular
      hemorrhage grades 3 to 4 (8.1%) and cystic leukomalacia (2.6%) were the most
      relevant brain ultrasonography findings. Rates of early- and late-onset
      septicemia were 5% and 29.4%, respectively. Further diagnoses were necrotizing
      enterocolitis (NEC; 6.9%) and persistent ductus arteriosus (PDA; 24.2%); 40.6% of
      the cases of NEC and 15.3% of those of PDA required surgery. In addition, 26.6%
      of the newborns required supplementary oxygen at 28 days of life. The number of
      newborns who had not recovered their birth weight at this age fell from 3.1% in
      2002 to 1.5% in 2005. Rates of prenatal steroid use, cesarean delivery, and main
      morbidities were comparable to figures cited for other patient series, although
      our BPD rate was among the lowest reported and nosocomial sepsis rate among the
      highest.

PMID- 19090454
TI  - New furanoditerpenoids from Croton jatrophoides.
AB  - Four furanoditerpenoids were isolated from roots of Croton jatrophoides
      (Euphorbiaceae) collected in Tanzania. In addition to the known compounds
      penduliflaworosin and teucvin (mallotucin A), a new teucvin isomer, which was
      named isoteucvin, and a furanoditerpenoid with a new skeleton, for which the name
      jatrophoidin was adopted, were isolated. Their structures were elucidated by
      spectroscopic methods such as ESI-MS and NMR, including (1)H-, (13)C-, and two
      dimensional NMR. The crystal structures of isoteucvin and jatrophoidin were
      solved using single-crystal X-ray diffraction, by which we also established the
      absolute configuration of jatrophoidin. The refined crystal structure of
      isoteucvin has the same (absolute) configuration as jatrophoidin, although the X
      ray diffraction data of isoteucvin were not conclusive with respect to the
      absolute configuration.

PMID- 19090457
TI  - Treatment of a pancreatic endocrine tumor by ethanol injection guided by
      endoscopic ultrasound.

PMID- 19090458
TI  - Severe high grade stenosing hyperkeratosis of the esophagus after ingestion of
      alkali: successful treatment by argon plasma coagulation.

PMID- 19090459
TI  - Ankaferd Blood Stopper as an effective adjunctive hemostatic agent for the
      management of life-threatening arterial bleeding of the digestive tract.

PMID- 19090460
TI  - Minimally invasive treatment of benign complete stenosis of colorectal
      anastomosis.

PMID- 19090461
TI  - Obstructive jaundice caused by hemobilia after liver biopsy.

PMID- 19090462
TI  - Gastrointestinal lymphoid pseudotumoral hyperplasia: report of four pediatric
      cases.

PMID- 19090463
TI  - A novel method for endoscopic removal of a fractured hydrophilic guide wire from
      an intrahepatic bile duct.

PMID- 19090464
TI  - Treatment of radiation-induced distal rectal lesions with argon plasma
      coagulation: use of a transparent cap.

PMID- 19090467
TI  - [Deployment advanced surgical education curriculum for the German military
      medical service].

PMID- 19090465
TI  - [Nobel Prize 2008: Viruses are more than infectious agents].

PMID- 19090468
TI  - [The future of conservative orthopedics in continuing education (interview by Dr.
      Rita Engelhardt)].

PMID- 19090475
TI  - [Knee prosthesis implantation--quantifying joint function].

PMID- 19090481
TI  - The use of complementary and alternative medicine (CAM) by Canadian occupational
      therapists.
AB  - The purpose of this study was to describe the proportion of occupational
      therapists currently using complementary and alternative medicine (CAM), or
      providing referrals to CAM practitioners, as well as the purposes of use/referral
      in one Canadian region. A questionnaire survey on CAM was sent through e-mail and
      post to 1123 Canadian occupational therapists. Content, construct and face
      validity, as well as response, desirability/social, and instrument bias were
      considered and controlled through study design. A response rate of 17.1% was
      achieved. Overall, 31.2% of respondents have used at least one form of CAM, with
      5.5% using > 1 form of CAM. Purposes for use focused on the treatment of
      symptoms. Reasons preventing CAM's use included lack of training (82.4%),
      interest (23%) and/or supporting evidence (22.3%). Considerations of
      incorporating CAM into occupational therapy focused on a client-centred and
      holistic approach to treatment (43-63.3%), ranking above legal/employer-related
      aspects (43-43.6%). Elaborations of negative responses indicated that further
      supporting evidence on forms of CAM and related research may result in changes of
      opinion. Therefore, further research on the use of CAM is needed, allowing for
      evidence-based decisions to be made.

PMID- 19090482
TI  - Ionic liquid-mediated selective extraction of lignin from wood leading to
      enhanced enzymatic cellulose hydrolysis.
AB  - Lignocellulose represents a key sustainable source of biomass for transformation
      into biofuels and bio-based products. Unfortunately, lignocellulosic biomass is
      highly recalcitrant to biotransformation, both microbial and enzymatic, which
      limits its use and prevents economically viable conversion into value-added
      products. As a result, effective pretreatment strategies are necessary, which
      invariably involves high energy processing or results in the degradation of key
      components of lignocellulose. In this work, the ionic liquid, 1-ethyl-3
      methylimidazolium acetate ([Emim][CH3COO]), was used as a pretreatment solvent to
      extract lignin from wood flour. The cellulose in the pretreated wood flour
      becomes far less crystalline without undergoing solubilization. When 40% of the
      lignin was removed, the cellulose crystallinity index dropped below 45, resulting
      in > 90% of the cellulose in wood flour to be hydrolyzed by Trichoderma viride
      cellulase. [Emim] [CH3COO] was easily reused, thereby resulting in a highly
      concentrated solution of chemically unmodified lignin, which may serve as a
      valuable source of a polyaromatic material as a value-added product.

PMID- 19090483
TI  - A stoichiometric model of Acidithiobacillus ferrooxidans ATCC 23270 for metabolic
      flux analysis.
AB  - A stoichiometric model of Acidithiobacillus ferrooxidans based on the sequenced
      genome from strain ATCC 23270 is derived and parameterized using genome/pathway
      databases. The model describes the main aspects of catabolism and anabolism. By
      the construction and utilization of the mathematical determination of the
      network, metabolic flux analysis is performed for such a bacterium for the first
      time and results are successfully verified by comparison to literature values.
      This first metabolic model of A. ferrooxidans is able to simulate the main
      aspects of metabolism and will be useful for further investigation and
      improvement of bioleaching procedures.

PMID- 19090484
TI  - Biocompatibility analysis of magnetic hydrogel nanocomposites based on poly(N
      isopropylacrylamide) and iron oxide.
AB  - With the growing interest in nanocomposites and their applications in biology and
      medicine, studies examining the biocompatibility of those materials are critical.
      Magnetic hydrogel nanocomposites based on poly(N-isopropylacrylamide) and iron
      oxide nanoparticles were fabricated via UV-polymerization with tetra(ethylene
      glycol) dimethacrylate acting as the crosslinking agent. In vitro
      biocompatibility analysis via NIH 3T3 murine fibroblast cytotoxicity was
      investigated. The fibroblasts in both direct and indirect contact with the
      hydrogels exhibited favorable cell viability indicating minimal cytotoxicity of
      the systems. In addition, swelling studies indicated that hydrogels with lower
      crosslink densities yield higher swelling ratios and that the presence of
      magnetic nanoparticle did not affect the swelling response of the hydrogel
      systems. Upon exposure to an alternating magnetic field, the hydrogel
      nanocomposites with iron oxide nanoparticles showed the capability for remote
      heating. This evaluation shows that these hydrogels have the potential to be used
      in biomedical applications such as drug delivery and hyperthermia for cancer
      treatment.

PMID- 19090485
TI  - Regulation of cathepsin X overexpression in H. pylori-infected gastric epithelial
      cells and macrophages.
AB  - Cathepsin X (CTSX) is strongly up-regulated in Helicobacter pylori-infected
      gastric mucosa and intestinal-type gastric cancer. The overexpression of CTSX is
      mediated predominantly by associated macrophages; depends on a functional type IV
      secretion system; and leads to increased migration of gastric epithelial cells.
      In the present study, we analysed the role of CagA in CTSX overexpression and
      identified H. pylori-induced inflammatory factors and signalling pathways
      required for stimulating CTSX expression by H. pylori. Gastric epithelial cells
      were co-cultured with macrophages in Transwell chambers of 0.4 microm pore size,
      enabling exchange of fluids but retracting H. pylori. N87 gastric epithelial
      cells were infected with H. pylori P1 wild-type strain in the presence of
      inhibitors for p38, JNK, and ERK1/2 signal transduction pathways. Furthermore,
      cytokines and growth factors were tested for their regulatory function using
      inhibitory antibodies, and their gene expression was studied by quantitative RT
      PCRs and western blots. CTSX is strongly up-regulated at both the mRNA and the
      protein levels by TNF-alpha, IL-1beta, IL-6, and IL-8, depending on cell type.
      All these cytokines were found to be increased by five- to ten-fold in
      macrophages by H. pylori infection of co-cultured N87 gastric epithelial cells.
      In macrophages, H. pylori up-regulated CTSX via ERK1/2 signalling pathways, and
      in N87 cells via JNK irrespective of p38 signalling. Our results suggest that H.
      pylori induced overexpression of CTSX in macrophages and epithelium through
      specific cytokines that are initiated by CagA-dependent pathways in a cell type
      dependent manner.

PMID- 19090487
TI  - Prenatal clinical characteristics of Casamassima-Morton-Nance syndrome.

PMID- 19090486
TI  - Hepatocyte-specific activation of NF-kappaB does not aggravate chemical
      hepatocarcinogenesis in transgenic mice.
AB  - The NF-kappaB signalling pathway plays important roles in liver organogenesis and
      carcinogenesis. Mouse embryos deficient in IKKbeta die in mid-gestation, due to
      excessive apoptosis of hepatoblasts. Although activation of the NF-kappaB
      signalling pathway has been demonstrated in human hepatocellular carcinoma, the
      role of NF-kappaB is controversial. Here, we have generated transgenic mice in
      which a constitutively active form of IKKbeta was expressed in a hepatocyte
      specific manner. Using electrophoretic mobility shift assay, we documented
      increased NF-kappaB activities and up-regulated levels of NF-kappaB downstream
      target genes, Bcl-xL and STAT5, in the transgenic mouse livers. These results
      confirmed that the NF-kappaB pathway was activated in the livers of the
      transgenic mice. However, there was no significant difference in tumour formation
      between transgenic and wild-type mice up to an age of 50 weeks. When we treated
      the transgenic mice with the chemical carcinogen diethylnitrosamine (DEN), we
      observed no significant differences in the incidence and size of liver tumours
      formed in these mice with and without DEN treatment at 35 weeks of age,
      suggesting that the activated NF-kappaB pathway in the livers of the transgenic
      mice did not enhance hepatocarcinogenesis. Interestingly, some of the transient
      transgenic embryos (E12.5) had abnormal excessive accumulation of nucleated red
      blood cells in their developing livers. In summary, NF-kappaB activation in
      hepatocytes did not significantly affect chemical hepatocarcinogenesis. In
      addition, the TTR/IKKCA transgenic mice may serve as a useful model for studying
      the role of NF-kappaB activation in hepatocarcinogenesis as well as inflammatory
      and metabolic diseases.

PMID- 19090488
TI  - Positive maternal anti-SSA/SSB antibody-related fetal right ventricular
      endocardial fibroelastosis without atrioventricular block, reversal of
      endocardial fibroelastosis.

PMID- 19090490
TI  - Intermittent watt-level ultrasonication facilitates vancomycin release from
      therapeutic acrylic bone cement.
AB  - Ultrasound holds promise for enhancing the vancomycin release from cement though
      the length of time when local drug level exceeded the minimum inhibitory
      concentration (T(>MIC)) was not prolonged by the previous protocol of milliwatt
      level ultrasonication. Here vancomycin-loaded cements were subjected to
      continuous watt-level ultrasonication (CUG), intermittent watt-level
      ultrasonication (IUG) or no ultrasonication (NUG) for 14 d during immersion in 40
      ml phosphate buffered saline (PBS) for 28 d. The T(>MIC) for IUG was more than
      three times that for NUG. In contrast, T(>MIC) for CUG was slightly shortened.
      The subtherapeutic release of vancomycin between 15 d and 28 d for IUG was one
      ninth that for NUG. The fitting equations indicated a significant enhancement on
      the burst release and the slow release for IUG; however, the continuous
      ultrasonication hampered the slow release. SEM images exhibited denser craters
      and pores with larger diameters and less residual drug in specimens from IUG
      relative to those from both CUG and NUG. Intermittent watt-level ultrasonication
      improved the ultrasound-enhanced vancomycin release from cement in view of the
      prolonged T(>MIC) and the inhibited subtherapeutic release compared with
      continuous ultrasonication. The mechanisms may be associated with the distinctive
      effects of detaching forces and pushing forces by acoustic microstreams.

PMID- 19090489
TI  - Elution kinetics, antimicrobial efficacy, and degradation and microvasculature of
      a new gentamicin-loaded collagen fleece.
AB  - Management of bone and soft tissue infections generally includes surgical
      procedures as well as attendant treatment and prevention with gentamicin-loaded
      fleeces. Conventional gentamicin-containing collagen fleeces currently in use are
      strongly acidic and exhibit limited biocompatibility thereby adversely affecting
      wound healing. To improve the antibiotic delivery system, a new phosphate
      buffered, gentamicin-loaded fleece with pH-neutral properties has been developed
      (Jason G). This study aimed at comparing the elution kinetics of gentamicin
      release and the antimicrobial efficacy of conventional fleeces with the newly
      developed fleece in vitro. In addition, degradation and microvasculature of
      implanted fleeces were examined in a rat model and assessed using histology, as
      well as detection of ED-1 and PECAM-expression using immunohistochemistry. We
      show that the phosphate-buffered fleeces have reduced release (p < 0.05) of the
      integrated gentamicin. However, all of the fleeces tested had a significant
      antimicrobial effect on the growth of Staphylococcus aureus, Escherichia coli,
      and Pseudomonas aeruginosa strains (p < 0.01). Among the fleeces tested, the new
      Jason G fleece had the weakest but nevertheless sufficient antimicrobial
      effectiveness. Evaluation of the antibiotic effect in the prevention of an
      infection showed no differences between the applied fleeces. Following surgical
      implantation of fleece in the backs of Wistar rats we observed, on day 5 after
      implantation, an increase in cell infiltration and microvascularization with the
      phosphate-buffered fleece as compared with conventional fleeces, which show
      necrotic cells on their surface. Unlike the acidic fleeces, on day 15 after
      implantation the pH-neutral fleece was resorbed widely. Here, we show that the
      new, pH-neutral, gentamicin-containing fleece Jason G exhibits good overall
      antimicrobial effectiveness against both gram-positive and gram-negative bacteria
      in vitro with improved degradation properties and microvasculature formation in
      vivo.

PMID- 19090491
TI  - Two-photon laser confocal microscopy of micropermeability of resin-dentin bonds
      made with water or ethanol wet bonding.
AB  - This study evaluated the micropermeability of six etch-and-rinse adhesives bonded
      to dentin. There were two principal groups: wet bonding with water or wet bonding
      with absolute ethyl alcohol. After bonding and the creation of composite build
      ups, the pulp chambers were filled with 0.1% lucifer yellow. The contents of the
      pulp chamber were kept under 20 cm H(2)O pressure to simulate pulpal pressure for
      3 h. The specimens were vertically sectioned into multiple 0.5-mm thick slabs
      that were polished and then examined using a two-photon confocal laser scanning
      microscope (TPCLSM). The results showed that specimens bonded with adhesives
      using the water wet-bonding condition all showed tracer taken up uniformly by the
      hybrid layer. This uptake of fluorescent tracer into the hybrid layer was
      quantified by computer software. The most hydrophobic experimental resins showed
      the highest fluorescent tracer uptake (ca. 1800 +/- 160 arbitrary fluorescent
      units/std. surface area). The most hydrophilic experimental resins showed the
      lowest tracer uptake into water-saturated hybrid layers. When ethanol wet-bonding
      was used, significantly less fluorescent tracer was seen in hybrid layers. The
      most hydrophilic experimental resins and Single Bond Plus showed little
      micropermeability. Clearly, ethanol wet-bonding seals dentin significantly better
      than water-wet dentin regardless of the adhesive in etch-and-rinse systems.

PMID- 19090492
TI  - Surface properties and blood compatibility of commercially available diamond-like
      carbon coatings for cardiovascular devices.
AB  - The aim of this study was to determine the relationships between the surface
      properties and blood compatibility of in-use diamond-like carbon (DLC) coatings
      for cardiovascular components. Commercially available DLC films were
      characterized with respect to surface topography and wettability, protein
      adsorption from human plasma, and platelets adhesion/activation. Fibrinogen (Fng)
      and human serum albumin (HSA) adsorbed onto the sample surfaces were in
      particular quantified as two of the main proteins involved in blood
      compatibility. A low tendency of platelets to spread and form aggregates onto the
      DLC-coated surfaces has been described and related to a low Fng-to-HSA adsorption
      ratio. This study provides evidence that the rapid and tenacious binding of
      albumin molecules to DLC materials tends to passivate the surfaces and to inhibit
      Fng adsorption, thus imparting thromboresistance to the carbon coatings by
      rendering the surfaces less adhesive and activating for platelets. Albumin
      preferential adsorption was ascribed to high chemical heterogeneity of the DLC
      sample surfaces. The DLC films tested present a favorable behavior as regards
      blood compatibility with respect to platelet thrombus formation by reason of
      their surface properties.

PMID- 19090494
TI  - Mechanically enhanced microcapsules for cellular gene therapy.
AB  - Microcapsules bearing a covalently cross-linked coating have been developed for
      cellular gene therapy as an improvement on alginate-poly(L-lysine)-alginate (APA)
      microcapsules that only have ionic cross-linking. In this study, two mutually
      reactive polyelectrolytes, a polycation (designated C70), poly([2
      (methacryloyloxy)ethyl]trimethylammonium chloride-co-2-aminoethyl methacrylate
      hydrochloride) and a polyanion (designated A70), poly(sodium methacrylate-co-2
      (methacryloyloxy)ethyl acetoacetate), were used during the microcapsule
      fabrication. Ca-alginate beads were sequentially laminated with C70, A70, poly(L
      lysine) (PLL), and alginate. The A70 reacts with both C70 and PLL to form a
      approximately 30 microm thick covalently cross-linked interpenetrating polymer
      network on the surface of the capsules. Confocal images confirmed the location of
      the C70/A70/PLL network and the stability of the network after 4 weeks
      implantation in mice. The mechanical and chemical resistance of the capsules was
      tested with a "stress test" where microcapsules were gently shaken in 0.003% EDTA
      for 15 min. APA capsules disappeared during this treatment, whereas the modified
      capsules, even those that had been retrieved from mice after 4-weeks
      implantation, remained intact. Analysis of solutions passing through model flat
      membranes showed that the molecular weight cut-off of alginate-C70-A70-PLL
      alginate is similar to that of alginate-PLL-alginate. Recombinant cells
      encapsulated in APA and modified capsules were able to secrete luciferase into
      culture media. The modified capsules were found to capture some components of
      regular culture media used during preparation, causing an immune reaction in
      implanted mice, but use of UltraCulture serum-free medium was found to prevent
      this immune reaction. In vivo biocompatibility of the new capsules was similar to
      the APA capsules, with no sign of clinical toxicity on complete blood counts and
      liver function tests. The increased stability of the covalently modified
      microcapsules coupled with the acceptable biocompatibility and permeability
      demonstrated their potential for use as immunoisolation devices in gene therapy.

PMID- 19090493
TI  - Host-derived loss of dentin matrix stiffness associated with solubilization of
      collagen.
AB  - Matrix metalloproteinases (MMPs) bound to dentin matrices are activated during
      adhesive bonding procedures and are thought to contribute to the progressive
      degradation of resin-dentin bonds over time. The purpose of this study was to
      evaluate the changes in mechanical, biochemical, and structural properties of
      demineralized dentin treated with or without chlorhexidine (CHX), a known MMP
      inhibitor. After demineralizing dentin beams in EDTA or phosphoric acid (PA), the
      baseline modulus of elasticity (E) of each beam was measured by three-point
      flexure. Specimens were pretreated with water (control) or with 2% CHX
      (experimental) and then incubated in artificial saliva (AS) at 37 degrees C for 4
      weeks. The E of each specimen was remeasured weekly and, the media was analyzed
      for solubilized dentin collagen at first and fourth week of incubation. Some
      specimens were processed for electron microscopy (TEM) immediately after
      demineralization and after 4 weeks of incubation. In EDTA and PA-demineralized
      specimens, the E of the control specimens fell (p < 0.05) after incubation in AS,
      whereas there were no changes in E of the CHX-pretreated specimens over time.
      More collagen was solubilized from PA-demineralized controls (p < 0.05) than from
      EDTA-demineralized matrices after 1 or 4 weeks. Less collagen (p < 0.05) was
      solubilized from CHX-pretreated specimens demineralized in EDTA compared with PA.
      TEM examination of control beams revealed that prolonged demineralization of
      dentin in 10% PA (12 h) did not denature the collagen fibrils.

PMID- 19090495
TI  - Analysis of bone mineral density and bone turnover in the presence of
      polymethylmethacrylate particles.
AB  - Polymethylmethacrylate (PMMA) particles generated from joint arthroplasties
      appear to contribute to aseptic implant loosening through inflammation-induced
      periprosthetic osteolysis. However, osteolysis appears to be multifactorial;
      whether a direct link exists between PMMA particles and osteolysis in vivo is
      unproven. With the aim to define the relationship between PMMA particles and
      osteolysis, the authors analyzed the bone mineral density, using microCT scans
      preoperatively, the first day postoperatively and then every 7-10 days for 32
      days, and bone turnover, using (18)F-fluoride positron emission tomography
      scanner (PET scan) at 8 weeks in four groups of mice that had undergone
      intramedullary femoral injection. The experimental group of five mice was
      injected with PMMA particles, and compared with two negative control groups (no
      injection and injection with the carrier, phosphate-buffered saline) and one
      positive control group (injection of PMMA particles contaminated with endotoxin).
      There was no significant change in bone mineral density with addition of PMMA
      particles, and no evidence of osteolysis. However, bone turnover was increased in
      the presence of PMMA particles. Even though a direct link between PMMA particles
      and osteolysis was not found in the short term, PMMA particles appear to
      influence the regenerative capacity of bone.

PMID- 19090496
TI  - On the (4)J(HH) long-range coupling in 2-bromocyclohexanone: conformational
      insights.
AB  - 2-Bromocyclohexanone is a model compound in which a 4JH2, H6 coupling constant is
      observed, whereas the corresponding 4JH2,H4 is absent. The observed long-range
      coupling is not only a result of the known W-type coupling, in the axial
      conformation, but also because of the less usual diaxial spin-spin coupling in
      the equatorial conformer. The carbonyl group plays a determining role in
      describing the coupling pathway, as concluded by natural bond orbital (NBO)
      analysis; although the sigma C2-H2-->sigma*C1(O)-C6 and sigma C6-H6 -
      >sigma*C1(O)-C2 interactions in the axial conformer contribute for transmitting
      the spin information associated with the W-type coupling, the strong sigma C2-H2-
      >pi*C=O and sigma C6-H6-->pi*C=O hyperconjugations in the equatorial conformer
      define an enhanced coupling pathway for 4JH2,H6,despite the inhibition of this
      coupling because of nO-->sigma*C(O)-C interaction and the large carbonyl angle.
      These findings provide the experimental evidence that orbital interactions
      contribute for the conformational isomerism of 2-bromocyclohexanone.

PMID- 19090498
TI  - Volunteerism and its role on International cancer control.

PMID- 19090497
TI  - Adaptation process and psychosocial resources of Chinese colorectal cancer
      patients undergoing adjuvant treatment: a qualitative analysis.
AB  - OBJECTIVES: To examine how Chinese patients with colorectal cancer (CRC)
      dynamically adapt to diagnosis and treatment and explore how patients evolve and
      deploy different resources throughout the illness trajectory. METHODS: Semi
      structured interviews were conducted on a purposive sample of 16 histologically
      diagnosed Chinese CRC patients about to complete or who had very recently
      completed all treatment without recurrence. Recorded interviews were transcribed
      verbatim and analyzed by using grounded theory techniques. RESULTS: Three major
      adaptation-related themes were identified: (1) utilization of medical resources,
      (2) transition of resource utilization, and (3) continuous resistance to demands.
      Initial prevailing fatalistic views of diagnosis associated predominantly with
      frequent medical surveillance and with respondents' weighting of treatment and
      expertise of medical professionals. As treatment progressed, there was a shift
      toward reliance on personal and social resources to field cancer-related demands
      concurrent with a gradual distancing from medical care. Upon treatment
      completion, fatalism re-emerged regarding disease recurrence, which, like
      diagnosis, was seen as not amenable to individual control, even with close
      adherence to medical follow-ups and dietary adjustment. Maintaining positive
      states of mind and good relationships with family and friends were cores
      strategies respondents adopted to preserve psychological well-being. CONCLUSIONS:
      Maintenance and enhancement of personal and social resources throughout the CRC
      trajectory may have considerably more utility than traditional descriptive
      studies hitherto suggested. Considering personal and social resources within
      dynamic rather than static models could avoid the pitfall of attributing
      maladaptive responses to initial dispositions and socioeconomic conditions that
      are seemingly unalterable and enduring over time.

PMID- 19090499
TI  - First-trimester maternal serum pregnancy-associated plasma protein-A and pre
      eclampsia.
AB  - OBJECTIVES: To examine the relationship between low maternal serum pregnancy
      associated plasma protein-A (PAPP-A) and uterine artery pulsatility index (UtA
      PI) at 11+0 to 13+6 weeks with subsequent development of pre-eclampsia (PE).
      METHODS: UtA-PI and serum PAPP-A were measured in women attending for routine
      care at 11+0 to 13+6 weeks of gestation. In the population, 156 (1.9%) women
      developed PE, including 32 (0.4%) in whom delivery was before 34 weeks (early PE)
      and 124 (1.5%) with delivery at 34 weeks or more (late PE); 7895 (98.1%) women
      had no PE. Regression analysis was used to examine which of the factors amongst
      maternal characteristics, log PAPP-A multiples of the median (MoM) and log UtA-PI
      MoM contributed to the prediction of PE. RESULTS: The median PAPP-A MoM was 1.002
      (interquartile range (IQR), 0.685-1.411) in the unaffected group, 0.555 (IQR,
      0.463-0.922) in early PE and 0.911 (IQR, 0.580-1.247) in late PE. Serum PAPP-A
      was below the 5th centile in 21.9% of early PE and 6.5% of late PE cases. The
      PAPP-A-related patient-specific risk for PE was strongly influenced by maternal
      characteristics. There was a significant association between log UtA-PI MoM and
      log PAPP-A MoM (P=0.001), and the detection rate of screening for PE by maternal
      variables and UtA-PI was not improved by inclusion of PAPP-A. Regression analysis
      was used to establish tables that allow modification of the maternal history and
      PAPP-A-related patient-specific risk for PE by the measurement of UtA-PI.
      CONCLUSIONS: Low PAPP-A is a marker for subsequent development of PE. The PAPP-A
      related patient-specific risk for PE can be modified by the measurement of UtA
      PI.

PMID- 19090500
TI  - Measurement of nuchal volume in the first trimester Down screening using three
      dimensional ultrasound.
AB  - OBJECTIVES: Screening of fetuses at 11 to 14 weeks of gestation for Down syndrome
      using stored volumes acquired by a three-dimensional (3D) scanner. METHOD: Thirty
      four healthy singleton fetuses were recruited consecutively and prospectively
      during routine first trimester scans in our unit. Two-dimensional (2D) images of
      nuchal translucency (NT), crown-rump length (CRL), and biparietal diameter (BPD)
      were obtained by following a standard protocol. The volume of the nuchal area
      (NV) was obtained by a 3D scanning machine. RESULTS: The mean time to perform a
      2D first trimester scan was 15.3 min, while the mean time to obtain and examine
      the stored volumes was 11.1 min (p<0.001) in a 3D scan. There were no significant
      differences in NT, CRL, and BPD between the two groups. Two cases with an NT
      thickness>2.5 mm also revealed increased volume data in the nuchal area. The
      Pearson's correlations between NT and CRL, BPD and CRL, NT and NV, and NV and CRL
      were moderate-to-high positive. CONCLUSION: The nuchal volume data and the
      standard curve in the first trimester may be possible markers for Down syndrome
      screening. 3D scans can also minimize the scanning time, providing views not
      easily following strict NT guidelines.

PMID- 19090501
TI  - A scoring system to differentiate malignant from benign masses in specific
      ultrasound-based subgroups of adnexal tumors.
AB  - OBJECTIVE: To investigate if the prediction of malignant adnexal masses can be
      improved by considering different ultrasound-based subgroups of tumors and
      constructing a scoring system for each subgroup instead of using a risk
      estimation model applicable to all tumors. METHODS: We used a multicenter
      database of 1573 patients with at least one persistent adnexal mass. The masses
      were categorized into four subgroups based on their ultrasound appearance: (1)
      unilocular cyst; (2) multilocular cyst; (3) presence of a solid component but no
      papillation; and (4) presence of papillation. For each of the four subgroups a
      scoring system to predict malignancy was developed in a development set
      consisting of 754 patients in total (respective numbers of patients: (1) 228; (2)
      143; (3) 183; and (4) 200). The subgroup scoring system was then tested in 312
      patients and prospectively validated in 507 patients. The sensitivity and
      specificity, with regard to the prediction of malignancy, of the scoring system
      were compared with that of the subjective evaluation of ultrasound images by an
      experienced examiner (pattern recognition) and with that of a published logistic
      regression (LR) model for the calculation of risk of malignancy in adnexal
      masses. The gold standard was the pathological classification of the mass as
      benign or malignant (borderline, primary invasive, or metastatic). RESULTS: In
      the prospective validation set, the sensitivity of pattern recognition, the LR
      model and the subgroup scoring system was 90% (129/143), 95% (136/143) and 88%
      (126/143), respectively, and the specificity was 93% (338/364), 74% (270/364) and
      90% (329/364), respectively. CONCLUSIONS: In the hands of experienced ultrasound
      examiners, the subgroup scoring system for diagnosing malignancy has a
      performance that is similar to that of pattern recognition, the latter method
      being the best diagnostic method currently available. The scoring system is less
      sensitive but more specific than the LR model.

PMID- 19090502
TI  - Validating a method that deals with missing drug information in the Saskatchewan
      Drug Plan database.
AB  - INTRODUCTION: An important limitation of Saskatchewan Drug Plan is the incomplete
      prescription data during an 18-month period (1987-1988), referred to here as the
      "black-hole". OBJECTIVE: To assess the impact of assuming drug non-exposure
      during the "black-hole" on measures of effect. METHODS: We used data from a
      matched case-control study carried out to assess the association between warfarin
      use and risk of prostate cancer. All subjects diagnosed with prostate cancer
      between 1981 and 2002 were matched to six controls. In order to avoid the "black
      hole", we included subjects whose cancer was diagnosed after 1994. Conditional
      logistic regression was used to calculate adjusted incidence rates and 95%
      confidence intervals (CIs) of prostate cancer in relation to warfarin. Two
      analyses were carried out: (a) without a "black-hole" and (b) with a random
      "black-hole" of 18 months imposed in the drug history, during which time subjects
      were assumed to be unexposed. RESULTS: Compared to non-use, the OR of prostate
      cancer for ever-use of warfarin in the preceding 5 years was 0.91 (95%CI: 0.81
      1.02) (without "black-hole") and 0.89 (95%CI: 0.79-1.01) (with "black-hole").
      Compared to non-use, cumulative use of 1, 2, 3, and 4 years were associated with
      ORs of 1.02, 0.94, 0.77, and 0.76, respectively in the analyses without a "black
      hole", and 1.02, 0.88, 0.75, and 0.76, respectively in the analyses with a "black
      hole" imposed. CONCLUSION: When using Saskatchewan Drug Plan data, assuming non
      exposure to warfarin during the "black-hole" has a minor effect on the measures
      of association.

PMID- 19090503
TI  - Effects of long-term exposure to ramelteon, a melatonin receptor agonist, on
      endocrine function in adults with chronic insomnia.
AB  - OBJECTIVE: To evaluate the effects of ramelteon, an MT(1)/MT(2) melatonin
      receptor agonist used to treat insomnia, on endocrine function in adults with
      chronic insomnia. METHODS: This was a double-blind, placebo-controlled, trial of
      adults (18-45 years) with chronic insomnia. Subjects received either ramelteon 16
      mg or placebo nightly for 6 months. Hormonal measures of the thyroid,
      reproductive, and adrenal axes were analyzed monthly and compared with baseline
      and placebo values. RESULTS: While isolated changes were detected at some time
      points, there were no consistent statistically significant differences between
      treatments on measures of thyroid function (total T4, free T4, TSH, and total
      T3), adrenal function (AM cortisol, and ACTH), or on most reproductive endocrine
      measures [LH, FSH, estradiol (women), total, and free testosterone (men)].
      Prolactin concentrations were increased overall in women in the ramelteon group
      compared with placebo (p = 0.003). No clinical effects of elevated prolactin were
      reported; average menstrual cycle length, duration of menses, and ovulation
      probability did not differ between groups. CONCLUSIONS: Long-term exposure to
      ramelteon 16 mg, a potent melatonin receptor agonist, resulted in mild, transient
      increase in prolactin, in women only, that were not associated with measurable
      reproductive effects. There were no consistent changes in other endocrine
      measures.

PMID- 19090504
TI  - Sexual health issues in Sudanese women before and during hormonal treatment for
      breast cancer.
AB  - OBJECTIVE: Recent Sudanese studies have focused on depression and anxiety in
      women treated for breast cancer (BrCa). Less is known about whether such women
      suffer from sexual disturbances due to different cancer treatments. This study
      compares BrCa patients with a healthy control group and assessed the impact of
      cancer treatment types. METHODS: The BrCa group included women treated for BrCa
      with mastectomies, chemotherapy and radiotherapy (N=100). Some received hormonal
      therapy (N=60) and others had not yet received it (N=40). The control group
      comprised women who had never had BrCa, non-BrCa (N=100). Outcomes were assessed
      using the Watts Sexual Function Questionnaire. RESULTS: It was found that many
      women treated for BrCa suffered from sexual disturbances before hormonal
      treatment while some regained sexual activity during hormonal treatment.
      Demographic data show negative correlation (P=0.03) between sexual function and
      age of the patients, positive correlation (P=0.002) between sexual function and
      educational level and positive correlation (P=0.031) as well between sexual
      function and the patient's length of marriage. CONCLUSION: This study helps to
      fill the gap in the literature about Sudanese women's sexuality, as many studies
      indicate the effect of some psychological disturbance (depression and anxiety)
      and ignoring the effect of sexual function in enhancing patient's quality of
      life.

PMID- 19090505
TI  - St. John's wort and Kava in treating major depressive disorder with comorbid
      anxiety: a randomised double-blind placebo-controlled pilot trial.
AB  - OBJECTIVE: We report the first randomised controlled trial (RCT) using a
      combination of St. John's wort (SJW) and Kava for the treatment of major
      depressive disorder (MDD) with comorbid anxiety. METHODS: Twenty-eight adults
      with MDD and co-occurring anxiety were recruited for a double-blind RCT. After a
      placebo run-in of 2 weeks, the trial had a crossover design testing SJW and Kava
      against placebo over two controlled phases, each of 4 weeks. The primary analyses
      used intention-to-treat and completer analyses. RESULTS: On both intention-to
      treat (p = 0.047) and completer analyses (p = 0.003), SJW and Kava gave a
      significantly greater reduction in self-reported depression on the Beck
      Depression Inventory (BDI-II) over placebo in the first controlled phase.
      However, in the crossover phase, a replication of those effects in the delayed
      medication group did not occur. Nor were there significant effects on anxiety or
      quality of life. CONCLUSION: There was some evidence of antidepressant effects
      using SJW and Kava in a small sample with comorbid anxiety. Possible explanations
      for the absence of anxiolysis may include a potential interaction with SJW, the
      presence of depression, or an inadequate dose of Kava.

PMID- 19090506
TI  - Stability of cognitive impairment in chronic schizophrenia over brief and
      intermediate re-test intervals.
AB  - OBJECTIVE: This study examined between- and within-subject stability of cognitive
      performance in individuals with chronic schizophrenia. METHODS: Thirty
      individuals with schizophrenia and 20 healthy controls matched by age, sex,
      education, and estimated IQ underwent repeated cognitive assessments at baseline
      and 30 days using computerized tests of psychomotor function, visual
      attention/information processing, non-verbal learning, and executive function.
      RESULTS: Compared to healthy controls, individuals with schizophrenia scored
      lower on all cognitive measures and demonstrated greater variability in cognitive
      performance. Within-subject variability in cognitive performance in both the
      schizophrenia and healthy control groups remained stable at brief (i.e., hours)
      and intermediate (i.e., one month) assessments. CONCLUSIONS: These results
      demonstrate the stability of between- and within-subject variability in cognitive
      performance in schizophrenia, and suggest that variability in cognitive
      performance may reflect an inherent characteristic of the disorder, rather than
      differences in test-retest reliability/error of cognitive measures.

PMID- 19090508
TI  - Improvement of peptide vectors for gene delivery with active targeting profiles
      for phosphatidylserine.
AB  - A cationic peptide, Td3701, which was derived from factor VIII that has affinity
      with phosphatidylserine (PS), showed efficient transfection ability for cells
      that express PS on the cell surface. PS is exposed on tumor cell surfaces
      therefore we have focused on PS as the target molecule for tumor specific gene
      delivery. In this article, to improve transfection efficiency and specificity in
      targeting tumor cells, some amino acid residues of Td3701 were replaced. The
      resulting peptide, Td3717, shows higher transfection efficiency (more than 30
      times that of Td3701). The transfection efficiency was dependent on the amount of
      PS on the cell surface, suggesting that Td3717 bound with plasmid DNA could
      recognize PS on the cell surface. Td3717 is expected to be useful as an efficient
      gene carrier molecule specific to PS-presenting tumor cells.

PMID- 19090509
TI  - Dyslexia, not disorder.

PMID- 19090507
TI  - The influence of acculturation and breast cancer-specific distress on perceived
      barriers to genetic testing for breast cancer among women of African descent.
AB  - OBJECTIVE: Rising health disparities are increasingly evident in relation to use
      of genetic services (including genetic counseling and testing) for breast cancer
      risk, with women of African descent less likely to use genetic services compared
      with Whites. Meanwhile, little is known regarding potential within-group
      acculturation and psychological differences underlying perceived barriers to
      genetic testing among women of African descent. METHODS: Hypothesized
      contributions of acculturation factors and breast cancer-specific distress to
      perceived barriers to genetic testing were examined with a statistical analysis
      of baseline data from 146 women of African descent (56% US born and 44% foreign
      born) meeting genetic breast cancer risk criteria and participating in a larger
      longitudinal study that included the opportunity for free genetic counseling and
      testing. Perceived barriers assessed included: (1) anticipation of negative
      emotional reactions, (2) stigma, (3) confidentiality concerns, (4) family-related
      worry, and (5) family-related guilt associated with genetic testing. RESULTS: In
      multivariate analyses, being foreign born was a significant predictor of
      anticipated negative emotional reactions about genetic testing (beta=0.26;
      SE=0.11; p=0.01). Breast cancer-specific distress scores (avoidance symptoms)
      were positively related to anticipated negative emotional reactions (beta=0.02;
      SE=0.005; p=<0.0001), confidentiality concerns (beta=0.02; SE=0.01; p=0.02), and
      family-related guilt (beta=0.02; SE=0.01; p=0.0009) associated with genetic
      testing. CONCLUSIONS: Results suggest an influence of acculturation and breast
      cancer-specific distress on perceived barriers to genetic testing among women of
      African descent. The potential utility of culturally tailored genetic counseling
      services taking into account such influences and addressing emotional and
      psychological concerns of women considering genetic testing for breast cancer
      should be investigated.

PMID- 19090511
TI  - Electrochemical study of dialcarb "distillable" room-temperature ionic liquids.
AB  - Electrode-dependent potential windows (see picture, GC=glassy carbon) are
      determined for five dialkylammonium carbamate (dialcarb) room-temperature ionic
      liquids in a systematic study of their physical and electrochemical properties.
      The viscosity and conductivity of the dialcarb ionic liquids, which are
      "distillable" at low temperature, are comparable to those of some conventional
      room-temperature ionic liquids. The physical and electrochemical properties of
      five "distillable" room-temperature ionic liquids from the dialcarb family
      (dialkylammonium carbamates formed from CO(2) and dialkyl amines) are
      systematically investigated. In particular dimethyl (DIMCARB), diethyl (DIECARB),
      dipropyl (DIPCARB), methylethyl (MEETCARB), and methylpropyl (MEPRCARB) carbamate
      ionic liquids are studied. The temperature dependence of the viscosity and
      conductivity of MEETCARB exhibit an Arrhenius-type relationship. Except for
      DIPCARB, which has too high a resistance, a reference potential scale is
      available by using the IUPAC recommended redox system, that is the
      cobalticenium/cobaltocene (Cc(+)/Cc) process, which exhibits an ideal reversible
      voltammetric response. Oxidation of decamethylferrocene, but not ferrocene, also
      is ideal in DIMCARB, DIECARB, MEETCARB, and MEPRCARB. The magnitudes of the
      potential windows of the electrochemically viable dialcarbs are investigated and
      follow the order of glassy carbon>Au>Pt>Hg. Diffusion coefficients of Cc(+),
      DmFc, and double-layer capacitance values are compared in each dialcarb. Despite
      the considerable viscosity of the dialcarbs, steady-state voltammetric behavior
      is achieved at a rotating disk electrode for rotation rates of 1000 rpm or
      higher.

PMID- 19090510
TI  - Evidence that thienamycin biosynthesis proceeds via C-5 epimerization: ThnE
      catalyzes the formation of (2S,5S)-trans-carboxymethylproline.

PMID- 19090513
TI  - Enantioselective induction of helical chirality in cyclooctapyrroles by metal
      complex formation.

PMID- 19090512
TI  - Coiled-coil lipopeptides mimicking the prehairpin intermediate of glycoprotein
      gp41.

PMID- 19090514
TI  - The ammosamides: structures of cell cycle modulators from a marine-derived
      Streptomyces species.

PMID- 19090516
TI  - Asymmetric alkaloid synthesis: a one-pot organocatalytic reaction to
      quinolizidine derivatives.

PMID- 19090515
TI  - A rationally designed aldolase foldamer.

PMID- 19090517
TI  - Biosynthesis and stability of coiled-coil peptides containing (2S,4R)-5,5,5
      trifluoroleucine and (2S,4S)-5,5,5-trifluoroleucine.

PMID- 19090518
TI  - New pacidamycin antibiotics through precursor-directed biosynthesis.
AB  - Pacidamycins, mureidomycins and napsamycins are structurally related uridyl
      peptide antibiotics that inhibit translocase I, an as yet clinically unexploited
      target. This potentially important bioactivity coupled to the biosynthetically
      intriguing structure of pacidamycin make this natural product a fascinating
      subject for study. A precursor-directed biosynthesis approach was employed in
      order to access new pacidamycin derivatives. Strikingly, the biosynthetic
      machinery exhibited highly relaxed substrate specificity with the majority of the
      tryptophan analogues that were administered; this resulted in the production of
      new pacidamycin derivatives. Remarkably, 2-methyl-, 7-methyl-, 7-chloro- and 7
      bromotryptophans produced their corresponding pacidamycin analogues in larger
      amounts than the natural pacidamycin. Low levels or no incorporation was observed
      for tryptophans substituted at positions 4, 5 and 6. The ability to generate
      bromo- and chloropacidamycins opens up the possibility of further functionalising
      these compounds through chemical cross-coupling in order to access a much larger
      family of derivatives.

PMID- 19090519
TI  - Identification of a toxic peptide through bidirectional expression of small RNAs.

PMID- 19090520
TI  - Design of cell-surface-retained polymers for artificial ligand display.

PMID- 19090521
TI  - Limiting current in a flowing-electrolyte-type droplet cell.
AB  - To the limit: Electrolyte flow accelerates the mass-transfer process in a droplet
      cell (see picture). The limiting current in the cell is expressed as a sum of
      hydrodynamic and stagnant terms. The current derived from the latter term
      indicates that convective mass transfer in the cell would be changed dramatically
      at a significantly small volumetric flow rate. Convective mass transfer in a
      flowing-electrolyte-type droplet cell (f-DC) is investigated for quantitative
      analysis of an electrode process and precise electrofabrication of
      microstructures using this device. The limiting current in the f-DC was expressed
      theoretically and its practical equation is investigated experimentally by cyclic
      voltammetry in solutions containing a redox mediator. The limiting-current
      equation in the f-DC derived experimentally could be expressed as a sum of
      hydrodynamic and stagnant terms. The current derived from the latter term of the
      f-DC is ten times larger than that in a conventional stagnant cell, thus
      indicating that the convective mass transfer in the cell would be changed
      dramatically at a small volumetric flow rate.

PMID- 19090522
TI  - A QM/MM investigation of thymine dimer radical anion splitting catalyzed by DNA
      photolyase.
AB  - On the mend: The repair reaction of the thymine dimer by DNA photolyase (see
      picture) is studied by hybrid quantum mechanical/molecular mechanical dynamics
      simulations based on the X-ray structure of the enzyme-DNA complex. The dynamics
      of splitting of the thymine dimer radical anion within the DNA photolyase active
      site is characterized. The model includes the protein environment. DNA photolyase
      is a highly efficient light-driven enzyme that repairs the UV-induced cyclobutane
      pyrimidine dimer in damaged DNA. Herein, we investigate the repair reaction of
      the thymine dimer by means of hybrid quantum mechanical/molecular mechanical
      (QM/MM) dynamics simulations based on the X-ray structure of an enzyme-DNA
      complex. In analogy to the self-repair reaction, we find that the splitting
      mechanism of the cyclobutane ring is asynchronously concerted and is complete
      within a few picoseconds upon electron uptake. A few distinct processes
      characterize the dynamics of splitting of the thymine dimer radical anion within
      the DNA photolyase active site: continuous solvation reordering of the catalytic
      region, proton transfer from Glu283 to the dimer, as well as tight interactions
      of the cationic side chains of Arg232 and Arg350 with the thymine dimer. This
      points to the important role of the active-site hydrogen bond and salt-bridge
      patterns in stabilizing the thymine dimer anion and slowing down the electron
      back-transfer process. Comparison of the repair efficiency with respect to the
      self-repair reaction is also discussed.

PMID- 19090523
TI  - Laser microbeams and optical tweezers in ageing research.
AB  - We show how a technique developed within the framework of physics and physical
      chemistry-in a true interdisciplinary approach-can answer questions in life
      sciences that are not solvable by using other techniques. Herein, we focus on
      blood-pressure regulation and DNA repair in ageing studies. Laser microbeams and
      optical tweezers are now established tools in many fields of science,
      particularly in the life sciences. A short glimpse is given on the wide field of
      non-age-research applications in life sciences. Then, optical tweezers are used
      to show that exerting a vertical pressure on cells representing the inner lining
      of blood vessels results in bursts of NO liberation concomitant with large
      changes in cell morphology. Repeated treatment of such human umbilical vein
      endothelial cells (HUVEC) results in stiffening, a hallmark of manifest high
      blood pressure, a disease primarily of the elderly. As a second application in
      ageing research, a laser microbeam is used to induce, with high spatial and
      temporal resolution, DNA damages in the nuclei of U2OS human osteosarcoma cells.
      A pairwise study of the recruitment kinetics of different DNA repair proteins
      reveals that DNA repair starts with non-homologous end joining (NHEJ), a repair
      pathway, and may only after several minutes switch to the error-free homologous
      recombination repair (HRR) pathway. Since DNA damages-when incorrectly repaired
      accumulate with time, laser microbeams are becoming well-used tools in ageing
      research.

PMID- 19090524
TI  - Pyridylalanine-containing hydroxamic acids as selective HDAC6 inhibitors.
AB  - We synthesized hydroxamic acids with a pyridylalanine substructure and identified
      them as selective inhibitors of human recombinant HDAC6. The in vitro selectivity
      was up to 25-fold for HDAC6 over HDAC1 and was confirmed by Western blotting to
      assess tubulin versus histone acetylation in cancer cells. Docking studies with
      an HDAC6 homology model suggested that the hydrophobic cap group of the
      inhibitors interacts with aromatic residues that form a sub-pocket near the
      entrance of the substrate binding channel. The HDAC6-selective compounds have
      less cytotoxicity toward cancer cells than do pan-HDAC inhibitors. The
      synergistic antiproliferative activity we showed with the proteasome inhibitor
      bortezomib suggests the potential for combination anticancer therapy with less
      general toxicity.

PMID- 19090525
TI  - Structural modifications of DAPY analogues with potent anti-HIV-1 activity.
AB  - A novel series of diarylpyrimidine analogues (DAPYs) featuring a naphthyl moiety
      at the C4 position were designed, with all compounds exhibiting strong activity
      against wild-type HIV-1.A novel series of diarylpyrimidine analogues (DAPYs)
      featuring a naphthyl moiety at the C4 position were synthesized and evaluated for
      their in vitro activity against HIV in MT-4 cells. All compounds exhibited strong
      activity against wild-type HIV-1. The most active compound showed activity
      against wild-type HIV-1 with an EC(50) value of 2.35 nM and against the double
      mutant strain (K103N+Y181C) with an EC(50) value of 6.6 microM, with a
      selectivity index greater than 60 000 against wild-type HIV-1. Additionally, some
      compounds also showed activity against HIV-2 (EC(50)=5.82 microM).

PMID- 19090526
TI  - pH-controllable supramolecular systems.
AB  - This Focus Review surveys representative examples of pH-controllable
      supramolecular systems with interesting features and state-of-the-art
      applications such as 1) conformational changes within individual molecules; 2)
      folding/unfolding of polymers; 3) simultaneous binding of cations and anions; 4)
      logic function; 5) ON-OFF switchable colorimetric sensing; 6) translocation of
      macrocycle-in-rotaxane molecules; 7) large-scale movement within molecules; and
      8) regulation of the substrate flow in nanocontainers. In particular, systems
      will be discussed that involve: pH-induced conformational changes of a
      resorcinarene cavitand and a bis(iron porphyrin) complex; pH control in assembly
      and disassembly of supramolecular systems stabilized with different major
      noncovalent interactions; pH-driven movements of interlocked molecules involving
      rotaxanes, molecular elevators, and molecular muscles; and, finally,
      multicomponent supramolecular systems immobilized on solid supports as pH
      responsive nanovalves for the controlled release of specific substrates. Recent
      advances in the understanding of pH-controllable supramolecular systems have led
      to the construction of meaningful molecular machines for electronic and
      biological applications that are amenable to control by simple perturbation with
      acids and bases.

PMID- 19090527
TI  - Unsynchronized diameter changes of double-wall carbon nanotubes during chemical
      vapour deposition growth.
AB  - Novel structural changes of double-wall carbon nanotubes (DWNTs) triggered by
      sudden swings of reaction condition have been elucidated. A quick temperature
      decrease or increase would lead to a decrease or increase, respectively, in the
      CH(4) decomposition rate and to reformation of catalyst metal particles. In
      particular, unsynchronized diameter changes of the inner and the outer tubes are
      observed in the DWNTs prepared by CoMo/MgO catalysts. We have found that the
      difference of the growth surroundings for the inner and outer tubes of DWNTs can
      consistently explain the observed unsynchronized diameter changes.

PMID- 19090528
TI  - Measuring social relational quality in colorectal cancer: the Social Relational
      Quality Scale (SRQS).
AB  - OBJECTIVES: Social relationships are central in Asian communities. Despite
      colorectal cancer (CRC) incidence increasing in Asian populations the roles of
      social activity in facilitating adjustment and optimizing coping resources in
      Asian peoples remains largely unknown. We derived and validated among Chinese CRC
      patients, an instrument assessing social relational quality to enable study of
      these social processes. METHODS: Qualitative interviews (n=16) generated 22-items
      subsequently administered to 166 Chinese CRC survivors. Principal components
      analyses identified underlying constructs. The draft instrument, plus measures of
      optimism, affect, physical symptoms, and perceived social support were
      administered to a second cohort of 234 newly diagnosed Chinese CRC patients.
      RESULTS: Three factors were extracted (54.44% of the total variance): Family
      Intimacy(7 items, 33.08%), Family Commitment (5 items, 14.17%), and Friendships
      (5 items, 7.19%). All subscales were internally consistent (alpha=0.75-0.82),
      exhibiting concurrent validity in negative correlations with anxiety and
      depression and positive correlations with physical and psychological well-being.
      Convergent validity was indicated by significant positive correlations with
      optimism, and divergent validity by insignificant inverse correlations with
      physical symptoms and moderate correlations with perceived social support.
      Hierarchical regressions revealed positive correlations of the three subscales
      with psychological well-being, controlling for perceived social support
      (beta=0.13-0.28). Good criterion validity was indicated. CONCLUSION: The Social
      Relational Quality Scale is a psychometrically sound self-report measure of
      social relational quality among Chinese CRC patients and needs further validation
      among other Asian groups.

PMID- 19090529
TI  - Building blocks for the synthesis of post-translationally modified glycated
      peptides and proteins.
AB  - Growing interest in synthetic peptides carrying post-traslational modifications,
      in general, and the Amadori modification in particular, raises the need for
      specific building blocks that can be used in stepwise peptide synthesis. Herein,
      we report the synthesis of N(alpha)-Fmoc-Lys-OH derivatives containing N(epsilon)
      1-deoxyfructopyranosyl moiety.

PMID- 19090531
TI  - Behavioral therapy intervention trial to improve sleep quality and cancer-related
      fatigue.
AB  - BACKGROUND: To determine whether sleep quality and fatigue associated with breast
      cancer adjuvant chemotherapy treatments can be improved with behavioral therapy
      (BT) [Individualized Sleep Promotion Plan (ISPP)] including modified stimulus
      control, modified sleep restriction, relaxation therapy, and sleep hygiene.
      METHODS: Randomized-controlled trial based on Piper Integrated Fatigue Model, 219
      stages I-IIIA breast cancer patients. Prior to the initial chemotherapy
      treatment, BT participants developed an ISPP plan that was regularly reinforced
      and revised. Controls received healthy eating information and attention.
      Pittsburgh Sleep Quality Index (PSQI), daily diary, actigraph, and Piper Fatigue
      Scale (PFS) data were collected 2 days prior, during the 7 days after each
      treatment, and 30 days after the last treatment. Repeated measures analysis of
      variance was used. RESULTS: Prior to chemotherapy, participants reported mild
      fatigue and fairly poor sleep quality. All variables changed over time. A group
      by time interaction was found for sleep quality (PSQI) improving in the BT group.
      Diary revealed group differences on number of awakenings, minutes awake after
      sleep onset, and sleep efficiency. Fatigue (PFS) was similar between groups.
      CONCLUSIONS: The BT group showed improved sleep quality over time and better
      sleep (diary). Perceptions of improved sleep quality over time are not
      consistently associated with diary or actigraph, or result in lower fatigue.

PMID- 19090532
TI  - Interplaying factors for the formation of photoswitchable beta-hairpins: the
      advantage of a flexible switch.
AB  - A series of peptidomimetics intended to promote the beta-hairpin motif have been
      studied. Structural variations include a turn region with and without a
      photoswitchable chromophore, and strands with amino acid side chains supporting
      various degrees of interstrand interactions for hairpin stabilisation. The
      propensity of the compounds to form beta-hairpins was evaluated experimentally by
      NMR spectroscopy, translational self-diffusion studies and CD spectroscopy. In
      the presence of hairpin stabilising interstrand interactions, the structurally
      flexible stilbene chromophore appeared to be well compatible with the imposed
      secondary structure.

PMID- 19090533
TI  - Psychotherapy with religious and spiritual clients: an introduction.
AB  - This invited issue of the Journal of Clinical Psychology: In Session is devoted
      to psychotherapy with religious and spiritual clients. After offering definitions
      of religion and spirituality, noting areas of potential convergence and
      differentiating nuances, the authors highlight the prevalence and types of
      spirituality among both clients and mental health professionals. They describe
      the historical and current context for examining approaches to psychotherapy with
      clients who endorse religion, experience spirituality within their religion, or
      define themselves as spiritual even if not religious. They then summarize the
      subsequent articles in this issue, which offer practical guidance for
      practitioners.

PMID- 19090535
TI  - Identification of the limitations on recombinant gene expression in CHO cell
      lines with varying luciferase production rates.
AB  - Mammalian cell lines are currently employed as one of the main cellular factories
      for the expression of recombinant protein-based drugs. The establishment of high
      producing cell lines typically begins with a heterogeneous starter population of
      cells, from which the highest producing cells are selected via empirical
      approaches. This approach is time consuming, and is likely to encounter natural
      upper limits imposed by the inherent biology of the cell lines in question. In an
      attempt to understand both the nature of the variability in populations of cells
      transfected with recombinant protein encoding DNA and the natural mechanisms of
      productivity limitation, we developed protocols for the detailed investigation of
      gene expression pathways in such cell lines. This novel approach was then applied
      to a set of clonal CHOK1 cell lines producing recombinant luciferase with varying
      productivities. Our results show that the initial limitation in these cell lines
      is at the transcriptional level, however in the highest producing cell line post
      translational mechanisms affecting both protein turnover and protein folding
      become severely limiting. The implications for the development of strategies to
      engineer cells for enhanced recombinant protein production levels are discussed.

PMID- 19090534
TI  - Reduction of Egf signaling decides transition from crown to root in the
      development of mouse molars.
AB  - Mouse, rat, and human molars begin to form their roots after the completion of
      crown morphogenesis. Though several signaling pathways and transcription factors
      have been implicated in the regulation of molar crown development, relatively
      little is known about the regulatory mechanisms involved in the transition from
      crown to root development. Tooth root formation is initiated by the development
      of Hertwig's epithelial root sheath (HERS) from the cervical loop in the enamel
      organ. In this study we examined the change in epidermal growth factor (Egf)
      signaling during this transition process. Immunohistochemical studies showed that
      the expression of Egf receptors in the enamel organ disappear gradually in the
      process and are not observed in HERS. Here, to examine the effect of Egf on the
      transition, we used the organ culture method to examine the root development. In
      the presence of Egf, stellate reticulum (SR) cells between the inner and outer
      epithelial layers in the enamel organ actively proliferated and maintained the
      enamel organ, and the formation of HERS was not observed. On the other hand, in
      either the absence of Egf or the presence of the inhibitor of Egf receptors, the
      SR cells disappeared and HERS formation started. Subsequently, root formation
      proceeded in the culture period. Therefore, disappearance of SR area may be a key
      event that controls the timing of onset of HERS formation, and Egf may be one of
      regulatory factors involved in the change from cervical loop epithelium to HERS
      during root development.

PMID- 19090536
TI  - Disposable bioprocessing: the future has arrived.
AB  - Increasing cost pressures are driving the rapid adoption of disposables in
      bioprocessing. While well ensconced in lab-scale operations, the lower operating/
      validation costs at larger scale and relative ease of use are leading to these
      systems entering all stages and operations of a typical biopharmaceutical
      manufacturing process. Here, we focus on progress made in the incorporation of
      disposable equipment with sensor technology in bioprocessing throughout the
      development cycle. We note that sensor patch technology is mostly being adapted
      to disposable cell culture devices, but future adaptation to downstream steps is
      conceivable. Lastly, regulatory requirements are also briefly assessed in the
      context of disposables and the Process Analytical Technologies (PAT) and Quality
      by Design (QbD) initiatives.

PMID- 19090541
TI  - Bilateral primary renal lymphoma with orbital metastasis in a child.
AB  - Primary renal lymphoma (PRL) is a rare condition and bilateral PRL even rarer.
      Most of these bilateral PRL have been reported in adults. We describe a 3-year
      old male with bilateral primary renal B cell lymphoma with orbital metastases. We
      discuss the difficulties in diagnosis and management of this rare presentation of
      lymphoma.

PMID- 19090542
TI  - Bioengineering Report. Fouling biofilm development: a process analysis.
      Biotechnol Bioeng., Vol. XXIII, Pp. 1923-60 (1981).

PMID- 19090543
TI  - Apoptosis-inducing activity of Helleborus niger in ALL and AML.
AB  - BACKGROUND: Helleborus niger is used in the adjuvant treatment of different
      tumors in anthroposophical medicine. Indications include various types of brain
      tumors in children, as well as prostate cancer, leukemia and lymphoma. Our aim
      was to investigate the therapeutic effects of these extracts apart from the
      traditional use. PROCEDURES: : We used an aqueous whole plant extract of H. niger
      in different cancer and leukemia cell lines and primary cells of patients with
      childhood ALL and AML and identified the main mechanisms of action. RESULTS: A
      strong inhibition of proliferation is caused by specific apoptosis induction,
      which is executed via the mitochondrial pathway and caspase-3 processing.
      Apoptosis could be detected in lymphoma (BJAB), leukemia (Reh, Nalm6, Sup-B15)
      and melanoma (Mel-HO) cells and overcomes a Bcl-2-mediated block of apoptosis. In
      primary cells of patients with childhood ALL and AML, which were partly poor
      responding to doxorubicin and daunorubicin, a strong apoptosis induction was
      determined. In combination with the vinca alkaloid vincristine, strong
      synergistic effects were detected in BJAB cells. CONCLUSION: We demonstrate in
      vitro efficacy of H. niger extract in cells of hematological malignancies; these
      studies should encourage in vivo experiments.

PMID- 19090544
TI  - A novel method for extracting DNA from chorionic villus samples for use in CVS
      PCR, which ensures complete villus dissociation.
AB  - OBJECTIVE: To demonstrate that glass disruption beads dissociate chorionic villus
      samples releasing DNA from mesenchymal and cytotrophoblast cells that is suitable
      for processing by CVS-PCR (rapid molecular aneuploidy testing). This method is
      quicker than conventional methods and may limit discrepancies between PCR and
      karyotype in certain types of placental mosaicism. METHOD: DNA was extracted from
      villus samples by mechanical disruption of the cells using glass beads. This
      method was compared to collagenase incubation followed by chelex extraction of
      the digested villus. PCR data generated were compared using standard criteria.
      RESULTS: DNA extracted by glass bead disruption generated data of equivalent
      quality to that obtained from DNA extracted using conventional collagenase and
      chelex-based extraction method. The case study demonstrates probable
      cytotrophoblast enrichment of a sample when processed by collagenase digestion
      and chelex incubation. Re-extraction of the digested sample by glass bead
      disruption resulted in cytotrophoblast and mesenchyme cells contributing to the
      supernatant. CONCLUSION: Glass bead disruption of chorionic villus samples is an
      effective, inexpensive and rapid DNA extraction method that dissociates villus
      ensuring that DNA from both cytotrophoblast and mesenchyme cells is represented
      in the supernatant. Extracted DNA produced is suitable for CVS-PCR and can be
      stored stably at - 20 degrees C.

PMID- 19090545
TI  - Prevention of homozygous beta thalassemia by premarital screening and prenatal
      diagnosis in India.
AB  - AIM: To determine the feasibility and acceptability of premarital screening for
      beta thalassemia/related hemoglobinopathies followed by prenatal diagnosis in
      India. MATERIALS AND METHODS: Premarital testing for thalassemia carrier state
      was carried out in (1) extended family members (EFM) of diagnosed cases of
      thalassemia/hemoglobinopathies, (2) unmarried adult cases of anemia attending the
      hospitals' outpatient department (OPD) and (3) adult college students (CG).
      Hemoglobin, red cell indices were measured by a cell counter and hemoglobin
      fractionation was carried out by high performance liquid chromatography (HPLC).
      In cases with HbA2>3.5%, or with variant hemoglobin, mutation screen was done by
      amplification refractory mutation system polymerase chain reaction (ARMS-PCR). In
      high-risk prospective couples, premarital genetic counseling was done and
      prenatal diagnosis possibilities were explained. RESULTS: The yield of carriers
      from EFM, OPD and CG groups was 78.17% (308/394), 19.51% (263/1348) and 4.04%
      (38/939), respectively. The number of prospective high-risk couples detected were
      154, 48 and 2 from EFM, OPD and CG, respectively. As much as 99% of prospective
      carrier couples married even after knowing their high-risk status and opted for
      prenatal diagnosis. The program averted the birth of 33 thalassemic children; 28
      in EFM group (by screening of 394 individuals), 4 in the OPD group (by screening
      1348 anemic patients), and 1 in CG group (by screening of 939 students).
      CONCLUSION: Premarital screening in extended family members, followed by prenatal
      diagnosis is acceptable and the most effective strategy for control of
      thalassemia in developing countries like India.

PMID- 19090546
TI  - Pseudohypopyon: Extramedullary relapse of acute myelogenous leukemia with poor
      prognosis.
AB  - An 11-month-old female presented to the emergency department with a 2-week
      history of fever, increasing fussiness, emesis, and decreased urine output. She
      was diagnosed with acute myelogenous leukemia. Systemic chemotherapy with
      intensified intrathecal cytarabine was started, and the patient achieved a
      clinical remission after the first course of induction. Towards the end of her
      second course of induction she developed pseudohypopyon in each eye on
      consecutive days, heralding a central nervous system relapse.

PMID- 19090547
TI  - Therapy and outcome of orbital primitive neuroectodermal tumor.
AB  - Primary orbital primitive neuroectodermal tumor (PNET) is rare with no reported
      series. We report six cases of orbital PNET treated at a tertiary care oncology
      center in northern India from 2003 to 2008. None of them had distant metastases.
      All were treated with neoadjuvant chemotherapy followed by exenteration in two,
      radiotherapy and adjuvant chemotherapy in five cases. Three out of six achieved
      complete remission at end of therapy with globe salvage in three and vision in
      two cases. Chemoradiotherapy may help us to avoid mutilating surgery in large or
      locally advanced tumors, allowing preservation of vision or the globe.

PMID- 19090548
TI  - Tracing survivors of childhood cancer in Australia.
AB  - BACKGROUND: A major challenge when establishing a retrospective cohort of
      childhood cancer survivors is maximizing the enrolment of individuals treated as
      children. In Australia, several public databases can facilitate tracing of
      childhood cancer survivors; these include the Births, Deaths and Marriage
      Registers (BDMR), the telephone white pages (EWP), and the Australian Electoral
      Roll (AER). The aim of this study was to evaluate the characteristics of
      survivors traced for a cohort study examining the late effects of childhood
      cancer. PROCEDURE: Eligible participants included 1,198 individuals treated for
      cancer during childhood at Sydney Children's Hospital. Of these, 1,156
      individuals were confirmed alive and subsequently traced by cross matching
      against the AER, BDMR, WP, and clinical records. Characteristics influencing the
      likelihood of tracing were evaluated using logistic regression analyses. RESULTS:
      Current addresses were obtained for 810 (70.1%) survivors. Overall, those
      diagnosed within the last decade were more easily traced than those diagnosed in
      an earlier decade (Test for trend, P < 0.01). In addition, older age at diagnosis
      and diagnosis of a sympathetic nervous system or renal malignancy were associated
      with a decreased likelihood of tracing in survivors, aged >/=18 years (P < 0.05).
      In survivors aged <18 years, age at diagnosis, sex, and cancer diagnosis were not
      associated with the likelihood of tracing (P > 0.05). CONCLUSIONS: Our findings
      show that cancer type and year of diagnosis are independent factors influencing
      the ability to trace survivors of childhood cancer. Linkage to public databases
      provides a unique opportunity to recruit a representative hospital-based cohort
      of childhood cancer survivors in Australia.

PMID- 19090549
TI  - The use of a protein and energy dense eicosapentaenoic acid containing supplement
      for malignancy-related weight loss in children.
AB  - BACKGROUND: The aim of nutritional therapy in cancer patients is to prevent
      weight loss and to improve functional capacity and quality of life. Clinical
      studies however, have continued to demonstrate that a reduction in body weight
      loss is difficult to achieve in cancer cachexia. Several studies have shown that
      supplementation with eicosapentaenoic acid (EPA), an omega-3 fatty acid, has anti
      cachectic effects in adult cancer patients. This study evaluated the clinical
      effects of a protein and energy dense EPA containing nutritional supplement in a
      group of pediatric cancer patients receiving active chemotherapy treatment.
      METHODS: The study was a prospective, randomized, single center, open-label
      design. Fifty-two patients diagnosed with pediatric malignant disease and
      receiving intensive chemotherapy were included. Thirty-three patients received a
      nutritional supplement containing EPA in addition to their regular food intake.
      Nineteen control patients did not receive supplementation. Patients were examined
      and their data (body weight, body mass index, and weight percentile) were
      recorded regularly once a month for 3 months. A subgroup of patients was
      evaluated for 6 months. RESULTS: At 3 months, there were significantly fewer
      patients in the treatment group as compared to controls that showed losses in
      body weight (P = 0.001), BMI (P = 0.002), and a negative deviation in weight
      percentile (P = 0.021). In addition, remission rate was significantly (P = 0.036)
      higher in the treatment group as compared to controls. CONCLUSIONS: This study
      demonstrates a decrease in cancer-induced weight loss in pediatric patients fed a
      protein and energy dense nutrition supplement containing EPA.

PMID- 19090550
TI  - TINF2 mutations in children with severe aplastic anemia.

PMID- 19090551
TI  - A question of quality in sickle cell disease.

PMID- 19090552
TI  - Pediatric Hodgkin lymphoma survivors at negligible risk for significant bone
      mineral density deficits.
AB  - BACKGROUND: We hypothesized that pediatric Hodgkin lymphoma (HL) survivors would
      have bone mineral density (BMD) deficits compared to their peers because of
      osteotoxic chemotherapy during the time of greatest BMD accretion. METHODS: We
      retrospectively reviewed records of HL survivors returning for follow-up between
      1990 and 2002. Of the 133 eligible survivors, 109 who underwent quantitative
      computed tomography (QCT) comprised the study group. QCT-determined BMD Z-scores
      were correlated with patient characteristics and therapeutic exposures by
      Wilcoxon rank sum or Chi-square tests. Logistic regression models were used to
      explore risk factors for diminished BMD. RESULTS: The study cohort was half male
      (50.5%) and 85.3% reported their race as white. Participants were representative
      of all survivors potentially eligible for study, except that more study
      participants were female, had hypothyroidism, and had received cyclophosphamide.
      Median age at diagnosis was 15.1 years (range, 3.1-20.7 years); median time
      between diagnosis and QCT was 7.5 years (range, 5.0-12.4 years). The proportion
      of HL survivors with BMD below the mean did not significantly differ from the
      general population (P = 0.503). However, those with BMD -1.5 SD and BMD -2.0 SD
      or lower (14.7% and 7.3%, respectively) exceeded that in the general population
      (6.7% and 2.3%, respectively; P < 0.001 for both degrees of severity). Males,
      diagnosed at 14 years or older, were at 6.5 times higher risk than females (OR
      95% CI: 1.24-34.14; P = 0.027) for BMD deficits. CONCLUSIONS: Overall, pediatric
      HL survivors had negligible BMD deficits. Male gender was associated with an
      increased risk of developing BMD deficits.

PMID- 19090554
TI  - Production and perception of sex differences in vocalizations of Wied's black
      tufted-ear marmosets (Callithrix kuhlii).
AB  - Males and females from many species produce distinct acoustic variations of
      functionally identical call types. Social behavior may be primed by sex-specific
      variation in acoustic features of calls. We present a series of acoustic analyses
      and playback experiments as methods for investigating this subject. Acoustic
      parameters of phee calls produced by Wied's black-tufted-ear marmosets
      (Callithrix kuhlii) were analyzed for sex differences. Discriminant function
      analyses showed that calls contained sufficient acoustic variation to predict the
      sex of the caller. Several frequency variables differed significantly between the
      sexes. Natural and synthesized calls were presented to male-female pairs. Calls
      elicited differential behavioral responses based on the sex of the caller.
      Marmosets became significantly more vigilant following the playback of male phee
      calls (both natural and synthetic) than following female phee calls. In a second
      playback experiment, synthesized calls were modified by independently
      manipulating three parameters that were known to differ between the sexes (low-,
      peak-, and end-frequency). When end-frequency-modified calls were presented,
      responsiveness was differentiable by sex of caller but did not differ from
      responses to natural calls. This suggests that marmosets did not use end
      frequency to determine the sex of the caller. Manipulation of peak-and low
      frequency parameters eliminated the discrete behavioral responses to male and
      female calls. Together, these parameters may be important features that encode
      for the sex-specific signal. Recognition of sex by acoustic cues seems to be a
      multivariate process that depends on the congruency of acoustic features.

PMID- 19090555
TI  - Reduction of appeasement-related affect as a concomitant of diazepam-induced
      aggression: evidence for a link between aggression and the expression of self
      conscious emotions.
AB  - Aggressive responding following benzodiazepine ingestion has been recorded in
      both experimental and client populations, however, the mechanism responsible for
      this outcome is unclear. The goal of this study was to identify an affective
      concomitant linked to diazepam-induced aggression that might be responsible for
      this relationship. Thirty males (15 diazepam and 15 placebo) participated in the
      Taylor Aggression Paradigm while covertly being videotaped. The videotapes were
      analyzed using the Facial Action Coding System with the goal of identifying
      facial expression differences between the two groups. Relative to placebo
      participants, diazepam participants selected significantly higher shock settings
      for their opponents, consistent with past findings using this paradigm. Diazepam
      participants also engaged in significantly fewer appeasement expressions
      (associated with the self-conscious emotions) during the task, although there
      were no group differences for other emotion expressions or for movements in
      general.

PMID- 19090556
TI  - Psychosocial interventions and quality of life in gynaecological cancer patients:
      a systematic review.
AB  - OBJECTIVE: Women with gynaecological cancer are at risk of poor quality of life
      outcomes. Although various psychosocial interventions have been developed to
      address these concerns, such interventions have not yet been systematically
      evaluated in this population. The current review provides an up-to-date and
      comprehensive summary of the evidence regarding the effectiveness of psychosocial
      interventions in women with gynaecological cancers. METHODS: Relevant studies
      were identified via Medline, CINAHL, and PsycINFO databases (1980 to June 2008),
      reference lists of articles and reviews, grey literature databases, and
      consultations with physicians and other experts in the field. Only controlled
      trials comparing a psychosocial intervention with a control group in a
      gynaecological cancer population, with at least one quality of life variable as a
      main outcome, were included in the review. Two authors independently assessed
      trial quality and extracted data. RESULTS: Twenty-two studies involving 1926
      participants were included. There was substantial variability in study quality
      and results. Evidence was mixed regarding intervention effects on social and
      sexual functioning, distress, depression, anxiety, attitude to medical care, self
      esteem and body image. Interventions generally did not improve physical or
      vocational outcomes. CONCLUSIONS: There was limited evidence in support of
      healing touch, whereas information-based interventions seemed largely unable to
      provide meaningful benefits. Cognitive-behavioural interventions had some
      positive effects. Counselling appeared to be the most promising intervention
      strategy for addressing quality of life concerns for women with gynaecological
      cancers.

PMID- 19090557
TI  - Successful use of adalimumab in treating cutaneous metastatic Crohn's disease:
      report of a case.

PMID- 19090558
TI  - Positron emission tomography (PET) used to image subclinical inflammation
      associated with ulcerative colitis (UC) in remission.
AB  - BACKGROUND: Positron emission tomography (PET) using 18-fluorodeoxyglucose (18
      FDG) is a noninvasive, functional imaging modality most often used to assess
      cancer. The aim of this study was to perform PET/computed tomography (CT) on
      patients with quiescent ulcerative colitis (UC) to understand the limits of this
      technology for assessing inflammatory activity. METHODS: We identified patients
      diagnosed with UC in a strictly defined remission state. PET/CT was performed in
      standard fashion, using approximately 10 mCi of 18-FDG with a 60-minute uptake
      delay. Uptake in each of 4 colonic segments (recto-sigmoid [r-s], descending,
      transverse, and ascending), and distal small bowel were scored on a 3-point scale
      (0 = no uptake or uptake <or=liver; 1 = uptake somewhat >liver; 2 = uptake much
      greater than liver). RESULTS: Ten patients participated in this study, 6 male.
      Eight had pancolitis, 1 had extensive colitis, and 1 had procto-sigmoiditis, with
      a median disease duration was 32 years. A PET scan was performed mean 37 days
      after endoscopy. Six patients had no increased 18-FDG uptake, 3 had increased
      uptake in the r-s region, 1 patient with r-s uptake also had ascending colon
      uptake, and 1 had ileal uptake with no colonic signal. CONCLUSIONS: In this
      study, PET demonstrated inflammatory activity in the colon despite negative
      endoscopic, histologic, and symptom assessment. This has important implications
      in the understanding of UC disease quiescence. Further exploration of this highly
      sensitive modality should be performed.

PMID- 19090560
TI  - Plasma chromogranin a in patients with inflammatory bowel disease.
AB  - BACKGROUND: Circulating chromogranin A (CgA) levels, a marker for neuroendocrine
      tumors including carcinoids, have recently been found elevated in some patients
      with inflammatory bowel disease (IBD), although their significance is unclear.
      Therefore, we aimed to evaluate CgA levels and their possible relationship with
      clinical and biochemical disease activity indexes in 119 IBD patients. METHODS:
      The study groups comprised 75 patients with ulcerative colitis, 44 with Crohn's
      disease, in both active and quiescent phases, and 85 controls. RESULTS: Mean CgA
      levels were significantly higher in IBD patients than in controls (20.4 +/- 14.0
      [SD] versus 11.3 +/- 4.3 U/L, P < 0.001), without any statistical significant
      difference among the IBD subgroups. However, CgA levels were above the normal
      range (20 U/L) in 25/45 patients with active IBD (55%; 95% confidence interval
      [CI]: 40%-70%) and in 18/74 patients with remission IBD (24%; 95% CI: 15%-36%) (P
      < 0.001, Fisher's test). Among biochemical parameters, CgA correlated with serum
      TNF-alpha levels (r(s) = 0.398, P < 0.001). CONCLUSIONS: High CgA levels can
      occur in IBD. The disease activity and TNF-alpha levels seem to influence the CgA
      pattern, which could reflect the neuroendocrine system activation in response to
      inflammation. From a clinical point of view, the possibility of high CgA levels
      in IBD should be taken into consideration when a carcinoid is suspected in such
      patients, since this event seems to be more frequent than previously considered.
      Indeed, revision of our 83 patients with gastrointestinal carcinoids, studied
      between 1997 and 2006, showed that 4 patients had IBD, with a prevalence of 4.8%,
      which is markedly higher than that of the general population.

PMID- 19090562
TI  - Inhibition of intestinal absorption of cholesterol by surface-modified
      nanostructured aluminosilicate compounds.
AB  - The aim of this work was to assess the ability of aqueous suspensions of surface
      modified nanostructured aluminosilicate (NSAS) compounds to reduce the intestinal
      absorption of cholesterol in a rat model. The rats were divided into 10 treatment
      groups which included several NSAS compounds at various doses, ezetimibe at 10
      mg/kg, stigmastanol at 50 mg/kg, and normal saline. All compounds and controls
      were independently administered by oral gavage and then a mixture of
      [(3)H]cholesterol and cold cholesterol in 10% Intralipid(R) was immediately
      administered orally to the animals. Systemic blood was sampled and the
      concentration of cholesterol in plasma was determined by means of radioactivity.
      Protonation of NSAS using an ion-exchange column resulted in significant
      inhibition of cholesterol absorption relative to the control group (31.5% and
      38.6% reduction in absorption of cholesterol for 50 and 100 mg/kg doses,
      respectively). Other surface-ion modifications of NSAS compounds did not show
      significant effect on intestinal cholesterol absorption. The inhibition of
      cholesterol absorption by ezetimibe was superior and by stigmastanol was equal to
      the effect of protonated NSAS in the doses investigated in this study. In
      conclusion, protonated NSAS material seems to inhibit significantly the
      intestinal absorption of dietary cholesterol in a rat model.

PMID- 19090563
TI  - Molecular dynamics simulations of fluid methane properties using ab initio
      intermolecular interaction potentials.
AB  - Intermolecular interaction energy data for the methane dimer have been calculated
      at a spectroscopic accuracy and employed to construct an ab initio potential
      energy surface (PES) for molecular dynamics (MD) simulations of fluid methane
      properties. The full potential curves of the methane dimer at 12 symmetric
      conformations were calculated by the supermolecule counterpoise-corrected second
      order Moller-Plesset (MP2) perturbation theory. Single-point coupled cluster with
      single and double and perturbative triple excitations [CCSD(T)] calculations were
      also carried out to calibrate the MP2 potentials. We employed Pople's medium size
      basis sets [up to 6-311++G(3df, 3pd)] and Dunning's correlation consistent basis
      sets (cc-pVXZ and aug-cc-pVXZ, X = D, T, Q). For each conformer, the
      intermolecular carbon-carbon separation was sampled in a step 0.1 A for a range
      of 3-9 A, resulting in a total of 732 configuration points calculated. The MP2
      binding curves display significant anisotropy with respect to the relative
      orientations of the dimer. The potential curves at the complete basis set (CBS)
      limit were estimated using well-established analytical extrapolation schemes. A 4
      site potential model with sites located at the hydrogen atoms was used to fit the
      ab initio potential data. This model stems from a hydrogen-hydrogen repulsion
      mechanism to explain the stability of the dimer structure. MD simulations using
      the ab initio PES show quantitative agreements on both the atom-wise radial
      distribution functions and the self-diffusion coefficients over a wide range of
      experimental conditions.

PMID- 19090561
TI  - Molecular genetics of ameloblast cell lineage.
AB  - Late tooth morphogenesis is characterized by a series of events that determine
      crown morphogenesis and the histodifferentiation of epithelial cells into enamel
      secreting ameloblasts and of mesenchymal cells into dentin-secreting
      odontoblasts. Functional ameloblasts are tall, columnar, polarized cells that
      synthesize and secrete a number of enamel-specific proteins. After depositing the
      full thickness of enamel matrix, ameloblasts shrink in size and regulate enamel
      maturation. Amelogenesis imperfecta (AI) is a heterogeneous group of inherited
      defects in enamel formation. Clinically, AI presents as a spectrum of enamel
      malformations that are categorized as hypoplastic, hypocalcified, or
      hypomaturation types, based upon the thickness and hardness of the enamel. The
      different types of AI are inherited, either as X-linked, autosomal-dominant, or
      autosomal-recessive traits. Recently, several gene mutations have been identified
      to cause the subtypes of AI. How these genes, however, coordinate their function
      to control amelogenesis is not understood. In this review, we discuss the role of
      genes that play definitive role on the determination of ameloblast cell fate and
      life cycle based on studies in transgenic animals.

PMID- 19090565
TI  - Extensive theoretical studies of a new energetic material: tetrazino-tetrazine
      tetraoxide (TTTO).
AB  - [1,2,3,4]Tetrazino-[5,6-e]-[1,2,3,4]tetrazine-[1,3,5,7]tetraoxide (TTTO, C2N8O4)
      was suggested to be a possible candidate of high energy density materials (HEDM).
      The most stable conformation of TTTO is a planar structure with C2h symmetry.
      Using various high-level ab initio methods including Gaussian-n, Complete Basis
      Set, Full Coupled Cluster, and W1U models of chemistry together with density
      functional theory based models, the enthalpies of formation of TTTO at 0 K and
      standard state were calculated precisely. Moreover, the rovibrational and nuclear
      magnetic resonance properties were predicted as well. The solid state TTTO was
      studied using the crystal packing models with the Dreiding force-filed and the
      plane-wave periodic local-density approximation density functional theory. Three
      stable polymorphous cells of TTTO have been found with either P212121 or P21/C
      symmetry. The high heat of formation (>200 kcal/mol), the high density (>2.0
      g/cm3), the planar nonpolar electronic structure, and the perfect oxygen balance
      lead TTTO be a very promising HEDM with exceptional performance. This work
      provides the first theoretical support for further experimental synthesis and
      testing.

PMID- 19090564
TI  - Polarizable empirical force field for nitrogen-containing heteroaromatic
      compounds based on the classical Drude oscillator.
AB  - The polarizable empirical CHARMM force field based on the classical Drude
      oscillator has been extended to the nitrogen-containing heteroaromatic compounds
      pyridine, pyrimidine, pyrrole, imidazole, indole, and purine. Initial parameters
      for the six-membered rings were based on benzene with nonbond parameter
      optimization focused on the nitrogen atoms and adjacent carbons and attached
      hydrogens. In the case of five-member rings, parameters were first developed for
      imidazole and transferred to pyrrole. Optimization of all parameters was
      performed against an extensive set of quantum mechanical and experimental data.
      Ab initio data were used for the determination of initial electrostatic
      parameters, the vibrational analysis, and in the optimization of the relative
      magnitudes of the Lennard-Jones (LJ) parameters, through computations of the
      interactions of dimers of model compounds, model compound-water interactions, and
      interactions of rare gases with model compounds. The absolute values of the LJ
      parameters were determined targeting experimental heats of vaporization,
      molecular volumes, heats of sublimation, crystal lattice parameters, and free
      energies of hydration. Final scaling of the polarizabilities from the gas-phase
      values by 0.85 was determined by reproduction of the dielectric constants of
      pyridine and pyrrole. The developed parameter set was extensively validated
      against additional experimental data such as diffusion constants, heat
      capacities, and isothermal compressibilities, including data as a function of
      temperature.

PMID- 19090566
TI  - Numerical examination of the extended phase-space volume-preserving integrator by
      the Nose-Hoover molecular dynamics equations.
AB  - This article illustrates practical applications to molecular dynamics simulations
      of the recently developed numerical integrators [Phys Rev E 2006, 73, 026703] for
      ordinary differential equations. This method consists of extending any set of
      ordinary differential equations in order to define a time invariant function, and
      then use the techniques of divergence-free solvable decomposition and symmetric
      composition to obtain volume-preserving integrators in the extended phase space.
      Here, we have developed the technique by constructing multiple extended-variable
      formalism in order to enhance the handling in actual simulation, and by
      constituting higher order integrators to obtain further accuracies. Using these
      integrators, we perform constant temperature molecular dynamics simulations of
      liquid water, liquid argon and peptide in liquid water droplet. The temperature
      control is obtained through an extended version of the Nose-Hoover equations.
      Analyzing the effects of the simulation conditions including time step length,
      initial values, boundary conditions, and equation parameters, we investigate
      local accuracy, global accuracy, computational cost, and sensitivity along with
      the sampling validity. According to the results of these simulations, we show
      that the volume-preserving integrators developed by the current method are more
      effective than traditional integrators that lack the volume-preserving property.

PMID- 19090567
TI  - First-principles calculations of the stability and electronic properties of the
      PbTiO3 (110) polar surface.
AB  - The structural and electronic properties of five terminations of cubic lead
      titanate (PbTiO3) (110) polar surface were investigated by first-principles total
      energy calculations using a periodic slab model. On the PbTiO termination, an
      anomalous filling of conduction band was observed, whereas on the O2 termination,
      two surface oxygen atoms formed a peroxo group, demonstrating that the electronic
      structures of the two stoichiometric terminations undergo significant changes
      with respect to bulk materials. However, for the three nonstoichiometric TiO-, Pb
      , and O-terminated surfaces, their electronic structures are very similar to
      bulk. Charge redistribution results for the five terminations confirmed that
      electronic structure and surface composition changes are responsible for their
      polarity compensation. However, which mechanism actually dominates the
      stabilization process depends upon energetic considerations. A thermodynamic
      stability diagram suggested that the two stoichiometric terminations are
      unstable; however, the three nonstoichiometric terminations can be stabilized in
      some given regions. Furthermore, this study indicates that the very different
      stabilities and surface states filling behaviors of the PbTiO3 (110) polar
      surface with respect to SrTiO3 and BaTiO3 ones seem to originate from the
      partially covalent characteristics of Pb-O pairs.

PMID- 19090568
TI  - Interactions of the "piano-stool" [ruthenium(II) (eta6-arene)(en)CL]+ complexes
      with water and nucleobases; ab initio and DFT study.
AB  - Piano stool ruthenium complexes of the composition [Ru(II)(eta6
      arene)(en)Cl](+/2+) (en = ethylenediamine) represent an emerging class of
      cisplatin-analogue anticancer drug candidates. In this study, we use
      computational quantum chemistry to characterize the structure, stability and
      reactivity of these compounds. All these structures were optimized at
      DFT(B3LYP)/6-31G(d) level and their single point properties were determined by
      the MP2/6-31++G(2df,2pd) method. Thermodynamic parameters and rate constants were
      determined for the aquation process, as a replacement of the initial chloro
      ligand by water and subsequent exchange reaction of aqua ligand by nucleobases.
      The computations were carried out at several levels of DFT and ab initio theories
      (B3LYP, MP2 and CCSD) utilizing a range of bases sets (from 6-31G(d) to aug-cc
      pVQZ). Excellent agreement with experimental results for aquation process was
      obtained at the CCSD level and reasonable match was achieved also with the
      B3LYP/6-31++G(2df,2pd) method. This level was used also for nucleobase-water
      exchange reaction where a smaller rate constant for guanine exchange was found in
      comparison with adenine. Although adenine follows a simple replacement mechanism,
      guanine complex passes by a two-step mechanism. At first, Ru-O6(G) adduct is
      formed, which is transformed through a chelate TS2 to the Ru-N7(G) final complex.
      In case of guanine, the exchange reaction is more favorable thermodynamically
      (releasing in total by about 8 kcal/mol) but according to our results, the rate
      constant for guanine substitution is slightly smaller than the analogous constant
      in adenine case when reaction course from local minimum is considered.

PMID- 19090569
TI  - Conceptual DFT properties-based 3D QSAR: analysis of inhibitors of the nicotine
      metabolizing CYP2A6 enzyme.
AB  - Structure-activity relationships of 46 P450 2A6 inhibitors were analyzed using
      the 3D-QSAR methodology. The analysis was carried out to confront the use of
      traditional steric and electrostatic fields with that of a number of fields
      reflecting conceptual DFT properties: electron density, HOMO, LUMO, and Fukui f-
      function as 3D fields. The most predictive models were obtained by combining the
      information of the electron density with the Fukui f- function (r2 = 0.82, q2 =
      0.72), yielding a statistically significant and predictive model. The generated
      model was able to predict the inhibition potencies of an external test set of
      five chemicals. The result of the analysis indicates that conceptual DFT-based
      molecular fields can be useful as 3D QSAR molecular interaction fields.

PMID- 19090570
TI  - The fate of free radicals in a cellulose based hydrogel: detection by electron
      paramagnetic resonance spectroscopy.
AB  - Cellulose derivatives are commonly used as gelling agents in topical and
      ophthalmic drug formulations. During the course of manufacturing, cellulose
      derivatives are believed to generate free radicals. These free radicals may
      degrade the gelling agent, leading to lower viscosity. Free radicals also may
      react with the active ingredient in the product. The formation of radicals in a
      3% hydrogel of hypromellose (hydroxypropyl methylcellulose) was monitored by
      electron paramagnetic resonance (EPR) spectroscopy and spin trapping techniques.
      Radicals were trapped with 5,5-dimethyl-1-pyrroline-N-oxide (DMPO) and
      quantitated by comparing the EPR intensity with 4-hydroxy-2,2,6,6
      tetramethylpiperidinyloxy (TEMPOL), a stable free radical. Typically, the
      hydrogels showed an initial increase in the radical concentration within 2 days
      after autoclaving, followed by a drop in radical concentration in 7 days. EDTA
      prevented the formation of free radicals in the hypromellose (HPMC) hydrogel,
      suggesting the involvement of metal ions in the generation of free radicals. The
      oxidizing potential of the hydrogel was estimated by measuring the rate at which
      methionine (a model for the protein active pharmaceutical ingredient) was
      degraded, and was consistent with the amount of radicals present in the gel. This
      study is the first report investigating the application of EPR spectroscopy in
      detecting and estimating free radical concentration in cellulose based hydrogels.

PMID- 19090571
TI  - Influence of ionization on the conformational preferences of peptide models.
      Ramachandran surfaces of N-formyl-glycine amide and N-formyl-alanine amide
      radical cations.
AB  - Ramachandran maps of neutral and ionized HCO-Gly-NH2 and HCO-Ala-NH2 peptide
      models have been built at the B3LYP/6-31++G(d,p) level of calculation. Direct
      optimizations using B3LYP and the recently developed MPWB1K functional have also
      been carried out, as well as single-point calculations at the CCSD(T) level of
      theory with the 6-311++G(2df,2p) basis set. Results indicate that for both
      peptide models ionization can cause drastic changes in the shape of the PES in
      such a way that highly disallowed regions in neutral PES become low-energy
      regions in the radical cation surface. The structures localized in such regions,
      epsilonL+* and epsilonD+* are highly stabilized due to the formation of 2-centre
      3-electron interactions between the two carbonyl oxygens. Inclusion of solvent
      effects by the conductor-like polarizable continuum model (CPCM) shows that the
      solute-solvent interaction energy plays an important role in determining the
      stability order.

PMID- 19090572
TI  - Chemical bonding in view of electron charge density and kinetic energy density
      descriptors.
AB  - Stalke's dilemma, stating that different chemical interpretations are obtained
      when one and the same density is interpreted either by means of natural bond
      orbital (NBO) and subsequent natural resonance theory (NRT) application or by the
      quantum theory of atoms in molecules (QTAIM), is reinvestigated. It is shown that
      within the framework of QTAIM, the question as to whether for a given molecule
      two atoms are bonded or not is only meaningful in the context of a well-defined
      reference geometry. The localized-orbital-locator (LOL) is applied to map out
      patterns in covalent bonding interaction, and produces results that are
      consistent for a variety of reference geometries. Furthermore, LOL
      interpretations are in accord with NBO/NRT, and assist in an interpretation in
      terms of covalent bonding.

PMID- 19090573
TI  - Multiple Markov transition matrix method: obtaining the stationary probability
      distribution from multiple simulations.
AB  - We herein propose the multiple Markov transition matrix method (MMMM), an
      algorithm by which to estimate the stationary probability distribution from
      independent multiple molecular dynamics simulations with different Hamiltonians.
      Applications to the potential of mean force calculation in combination with the
      umbrella sampling method are presented. First, the performance of the MMMM is
      examined in the case of butane. Compared with the weighted histogram analysis
      method (WHAM), the MMMM has an advantage with respect to the reasonable
      evaluation of the stationary probability distribution even from nonequilibrium
      trajectories. This method is then applied to Met-enkephalin nonequilibrium
      simulation.

PMID- 19090576
TI  - Microbial electrode BOD sensors. Biotechnol Bioeng. Vol. XIX, Pgs. 1535-47
      (1977).

PMID- 19090577
TI  - Reaction mechanism of palladium-catalyzed silastannation of allenes by density
      functional theory.
AB  - The reaction mechanism of Pd(0)-catalyzed allenes silastannation reaction is
      investigated by the density functional method B3LYP. The overall reaction
      mechanism is examined. For the allene insertion step, the Pd-Si bond is preferred
      over the Pd-Sn bond. The electronic mechanism of the allene insertion into Pd-Si
      bond to form sigma-vinylpalladium (terminal-insertion) and sigma-allylpalladium
      (internal-insertion) insertion products is discussed in terms of the electron
      donation and back-donation. It is found that the electron back-donation is
      significant for both terminal- and internal-insertion. During allene insertion
      into Pd-Si bond, internal-insertion is preferred over terminal-insertion. By
      using methylallene, the regio-selectivity for the monosubstituted allene
      insertion into Pd-Si and Pd-Sn bond is analyzed.

PMID- 19090578
TI  - The use of oxygen uptake rate to monitor discovery of microbial and enzymatic
      biocatalysts.
AB  - Arising from the requirement for discovery of novel biocatalysts with unusual
      properties, a process was developed which uniquely combines aspects of continuous
      culture with the measurement of oxygen uptake. This adaptation of the chemostat
      can be used to facilitate the isolation of a number of microorganisms with
      desirable properties, particularly those with useful metabolic capabilities
      and/or enzymes. The technique was also used to provide feedback on the metabolic
      status of a microbial population and increase the feed flow rate (i.e., dilution
      rate) thereby enabling the isolation of microorganisms with enhanced 1,3
      propanediol dehydrogenase activity. The use of oxygen uptake as an indicator of
      cellular activity enables indirect measurement of substrate utilization and
      provides a real-time online assessment of the status of microbial enrichment or
      evolutionary processes and provides an opportunity, through the use of feedback
      systems, to control these processes. To demonstrate the utility of the technique,
      oxygen uptake rate (OUR) was compared with a range of conventional analytical
      techniques that are typically used to monitor enrichment/evolutionary processes
      and showed good correlation. Further validation was demonstrated by monitoring a
      characterizable microbial population shift using OUR. The population change was
      confirmed using off-line analytical techniques that are traditionally used to
      determine microbial activity. OUR was then used to monitor the enrichment of
      microorganisms capable of using a solvent (1-methyl-2-pyrrolidinone) as the sole
      source of carbon for energy and biomass formation from a heterogeneous microbial
      population. After purification the microorganisms taken from the enrichment
      process were able to completely utilize 1 g L(-1) 1-methyl-2-pyrrolidinone within
      24 h demonstrating that the technique had correctly indicated the enriched
      population was capable of growth on 1-methyl-2-pyrrolidinone. The technique
      improves on conventional microbial enrichment that utilizes continuous culture by
      providing a real-time assessment of the enrichment process and the opportunity to
      use the OUR output for automated control and variation of one or more growth
      parameters.

PMID- 19090581
TI  - Post-last glacial maximum expansion from Iberia to North Africa revealed by fine
      characterization of mtDNA H haplogroup in Tunisia.
AB  - The first large-scale fine characterization of Tunisian H lineages clarifies that
      the post-Last glacial maximum expansion originating in Iberia not only led to the
      resettlement of Europe but also of North Africa. We found that 46% of 81 Tunisian
      H lineages subscreened for 1,580 bp in mtDNA coding region were affiliated with
      H1 and H3 subhaplogroups, which are known to have originated in Iberia. Although
      no signs of local expansion were detected, which would allow a clear dating of
      their introduction, the younger and less diverse Tunisian H1 and H3 lineages
      indicate Iberia as the radiating centre. Major contributions from historical
      migrations to this Iberian genetic imprint in Tunisia were ruled out by the mtDNA
      gene pool similarity between Berber/Arab/cosmopolitan samples and some
      "Andalusian" communities, settled by the descendents of the "Moors" who once
      lived in Iberia for 10 centuries (between 8th and 17th centuries), before being
      expelled to Tunisia.

PMID- 19090582
TI  - GridMAT-MD: a grid-based membrane analysis tool for use with molecular dynamics.
AB  - GridMAT-MD is a new program developed to aid in the analysis of lipid bilayers
      from molecular dynamics simulations. It reads a GROMACS coordinate file and
      generates two types of data: a two-dimensional contour plot depicting membrane
      thickness, and a polygon-based tessellation of the individual lipid headgroups.
      GridMAT-MD can also account for proteins or small molecules within the headgroups
      of the lipids, closely approximating their occupied lateral area. The program
      requires no installation, is fast, and is freely available.

PMID- 19090583
TI  - Face validity and reliability of the first digital assessment scheme of pelvic
      floor muscle function conform the new standardized terminology of the
      International Continence Society.
AB  - AIMS: To test the face validity and reliability of a new digital pelvic floor
      muscle function (PFMF) assessment scheme that was designed on the basis of the
      recently standardized terminology of the International Continence Society.
      METHODS: Study participants comprised 41 women, age 18-85 years. Data on age and
      parity were obtained. Face validity of the new assessment scheme was tested by
      three senior and one junior pelvic physiotherapists, using the Delphi technique.
      PFMF of each woman was assessed four times by three specially trained pelvic
      physiotherapists. Examiners were blinded to parity and other findings. To test
      reliability, Kappa (K) was used for the dichotomous variables and Weighted Kappa
      (K(w)) for the items with more than two categories. RESULTS: Mean age of the
      women was 41 years (SD 10.5); 14 were nulliparous (34.1%), 6 primiparous (14.6%),
      and 21 multiparous (51.2%). The new assessment scheme showed satisfactory face
      validity and intra-observer reliability but low inter-observer reliability.
      CONCLUSIONS: The new assessment scheme based on the terminology of the ICS showed
      satisfactory face validity and intra-observer reliability. It can therefore be
      considered suitable for use in clinical practice. More detailed redefinition of
      the described outcome measures is necessary to improve the inter-observer
      reliability.

PMID- 19090584
TI  - Predictive value of the penilo-cavernosus reflex.
AB  - AIMS: To determine the predictive values and specificity of clinical and
      neurophysiologic testing of the penilo-cavernosus reflex. METHODS: A group of 22
      control men and a group of 53 men with chronic cauda equina lesions (patients)
      were studied. The penilo-cavernosus reflex was elicited clinically and measured
      neurophysiologically using single and double electrical stimulation. The sensory
      threshold, reflex threshold and stimulation strength in all controls, and latency
      of the response in all subjects, were compared to reference intervals.
      Sensitivity, specificity, positive and negative predictive values, and likelihood
      ratios of the penilo-cavernosus reflex testing were calculated. RESULTS:
      Sensitivity of the penilo-cavernosus reflex was 72-83% and 81-83%, specificity 52
      57% and 90-91%, positive predictive value 83-97% and 95-96%, negative predictive
      value 52-57% and 66-68%, and likelihood ratios 1.9-2.8 and 8.3-9.0 for clinical
      (circumcised subjects: included/excluded; reflex pathologic when diminished/non
      elicitable) and neurophysiologic testing (using three stimulation modalities),
      respectively. Specificities of the sensory threshold, reflex threshold and
      stimulation strength were approximately 90% or higher. CONCLUSIONS: The present
      study demonstrated higher specificity, predictive values and likelihood ratios of
      neurophysiologic testing of the penilo-cavernosus reflex compared to clinical
      testing. The results support the use of clinical penilo-cavernosus reflex testing
      as an addition to bladder emptying difficulties and saddle sensory loss as
      criteria for patient referral for uro-neurophysiologic examination, and
      measurement of the reflex as a valuable part of such testing. Neurourol.
      Urodynam. 28:390-394, 2009. (c) 2008 Wiley-Liss, Inc.

PMID- 19090585
TI  - Urinary incontinence among institutionalized oldest old Chinese men in Taiwan.
AB  - AIMS: To explore prevalence and related factors for urinary incontinence (UI)
      among the oldest old institutionalized Chinese men in Taiwan. METHODS: All
      residents living in Banciao Veterans Care Home were invited for study. UI was
      defined as urinary leakage at least once weekly. Additional data items from the
      Minimum Data Set (MDS Nursing Home Chinese Version 2.1) were used to explore
      impact associated with physical function, cognitive status and quality of life
      (social engagement, SocE). Depressive symptoms were screened by the Short Form
      Geriatric Depression Scale. RESULTS: Data from 594 male residents (mean age: 80.9
      +/- 5.3 years) were analyzed. Among all study subjects, 92.8% were functionally
      independent, 20.4% had certain cognitive impairment and 8.2% had depressive
      symptoms. The prevalence of UI in the Banciao Veterans Care Home was 10.1%.
      Compared with residents without UI, subjects with UI had poorer physical
      function, cognitive status, and more depressive symptoms. The mean SocE score was
      1.5 +/- 1.3, and was similar between UI (+) and UI (-) subjects (1.4 +/- 1.2 vs.
      1.6 +/- 1.3, P = 0.411). By multivariate logistic regression, poorer physical
      functional status, cognitive impairment and depressive symptoms were independent
      risk factors for UI (P < 0.05). CONCLUSIONS: Poorer physical function, poorer
      cognitive status and depressive symptoms were all statistically significant
      independent risk factors for UI. However, SocE score (proxy indicator of quality
      of life) did not differ between subjects with and without UI. Further
      investigations are needed to evaluate the impact of UI on quality of life among
      oldest old institutionalized Chinese men in Taiwan.

PMID- 19090586
TI  - Urodynamic findings and functional or anatomical obstructions in children who
      developed bladder diverticula after reimplantation of the ureter.
AB  - OBJECTIVE: To study the clinical and urodynamic parameters of children who
      developed bladder diverticula (BD) after ureteral reimplantation. MATERIALS AND
      METHODS: We have reviewed records of 15 children who underwent ureteric
      reimplantation, possibly with diverticulectomy between January 1998 and October
      2004, who postoperatively developed BD and compared the results with 25 patients,
      surgically treated for primary vesicoureteric reflux (VUR) without BD development
      after reimplantation. A total of 737 reimplantations was performed in 492
      patients. Of the 15 patients and 25 controls we reviewed voiding history and free
      uroflowmetry, urodynamic parameters, findings on urethrocystoscopy, VCUG and
      signs of dysfunctional or anatomical obstruction. RESULTS: Of the fifteen
      patients with a postoperative diverticulum, one patient (7%) had an infravesical
      obstruction in combination with a normal voiding pattern, nine patients (60%) had
      severe dysfunctional voiding and two patients (13%) had both. Three patients had
      no infravesical obstruction nor dysfunctional voiding. Urodynamically the mean
      Pmax postoperatively was 96.8 (cm-H(2)O) in the obstructed patients (BD-group)
      (in controls 50.0 cm-H(2)O) and 95.6 (cm-H(2)O) for the dysfunctional voiders (in
      controls 61.8 cm-H(2)O). The difference between the Pmax values of BD-group and
      controls was significant on the 95% C.I. (P < 0.01). CONCLUSION: Dysfunctional
      voiding and infravesical obstruction in children appear to be important risk
      factors for acquired BD. Voiding pressures are significantly higher in patients
      that developed BD. Cognitive bladder training to normalize voiding pressures
      should be done before surgery if feasible. Special attention should be paid to
      the persistence of an infravesical obstruction.

PMID- 19090587
TI  - Can the use of different parameters and waveforms improve the results of
      intravesical electrical stimulation: a pilot study in the rat.
AB  - AIM: Intravesical electrical stimulation (IVES) with square wave pulses, low
      frequencies and short pulse durations has been used for decades in diagnosis and
      treatment of lower urinary tract dysfunction. The results are not always
      satisfying. Several parameters have been studied before but not the use of other
      waveforms and the effect of electrical charge. This study compares the effect of
      changing waveforms, frequencies, pulse durations, amplitudes and derived
      parameters in IVES. METHODS: IVES, performed in seven female Sprague-Dawley rats,
      was given for 10 sec with constant current unipolar square or sawtooth pulses
      with different pulse durations (10, 20, or 100 msec), frequencies (5, 20, or 10
      Hz) and amplitudes (2, 4, 6, and 8mA). Bladder pressure was recorded. Electrical
      charge and power were calculated. RESULTS: Stimulation with the same frequency,
      same pulse duration and same amplitude showed significantly higher maximal
      pressure rises (max DeltaP) for square wave (all P < 0.05). Stimulation with the
      same frequency, same pulse duration and same electrical charge, gave no different
      max DeltaP for both waveforms (all P > 0.05). The charge and power could be
      reduced without changing max DeltaP, by lowering frequencies and/or shortening
      pulse durations. CONCLUSIONS: Sawtooth pulses are equally effective as square
      pulses for inducing detrusor contraction during IVES with the same electric
      charge. Frequency and pulse duration had, in this study, a minor influence on the
      efficacy of IVES. Lower frequency and/or shorter pulse duration results in lower
      charge and power without changing stimulation efficacy. This finding can be
      important for the battery life of implanted stimulators and for patient's
      comfort.

PMID- 19090588
TI  - Percutaneous tibial nerve stimulation produces effects on brain activity: study
      on the modifications of the long latency somatosensory evoked potentials.
AB  - OBJECTIVE: Long-latency somatosensory evoked potentials (LL-SEP) provide
      information on the function of somatosensory cortical structures. Percutaneous
      tibial nerve stimulation (PTNS) is indicated in the treatment of lower urinary
      tract dysfunction. Aim of this study was to evaluate LL-SEP in patients with
      overactive bladder syndrome (OAB) treated by means of PTNS. METHODS: Sixteen
      female patients with a diagnosis of pharmacoresistant OAB underwent PTNS while
      eight female patients with the same diagnosis underwent sham stimulation. LL-SEP
      were performed at baseline and at the end of PTNS or sham stimulation. Peak
      latency and peak to peak amplitude of P80, P100, and P200 waves were measured.
      RESULTS: Mean latency of P80, P100, and P200 and mean amplitude of P200 did not
      show any significant change after both stimulation. Mean amplitude of P80 and
      P100 waves increased significantly after PTNS while it did not vary after sham
      stimulation. CONCLUSION: The P80 and P100 amplitude increase might reflect long
      term modifications in synaptic efficiency through the somatosensory pathway. The
      plastic reorganization of cortical network triggered by peripheral
      neuromodulation can be hypothesized as a mechanism of action of PTNS. Further
      studies are needed to correlate LL-SEP modifications after PTNS with the success
      of the treatment.

PMID- 19090589
TI  - Impact of urinary incontinence on the psychological burden of family caregivers.
AB  - AIMS: The present study was conducted to assess the impact of urinary
      incontinence on the psychological burden of family caregivers providing care to
      disabled family members with urinary incontinence. MATERIALS AND METHODS: This
      survey was conducted using an Internet panel for family caregivers in Japan,
      consisting of 7,316 members. We requested the members to respond to an online
      questionnaire to assess the impact of urinary incontinence on the burden of
      caregivers. The questionnaire included basic characteristics, and the Japanese
      version of the Zarit Caregiver Burden Interview (ZBI) comprising 22 questions
      related to the impact of the patient's disabilities on the burden of their
      caregivers. Additionally, the participants were asked to include the level of
      care need, ranging from 0 to 5 according to the grade of disability of the cared
      individuals. RESULTS: Relevant data obtained from 757 caregivers were analyzed.
      Of these caregivers, 452 provided care to family members with urinary
      incontinence (group 1), and 305 provided care to those without urinary
      incontinence (group 2). The mean total ZBI score was significantly higher in
      group 1 than in group 2 (mean, 40.7 vs. 34.7, P < 0.001). The difference in the
      scores for each item was also significant in 20 of the 22 items. With regard to
      the level of care need, irrespective of the level, the ZBI scores in group 1
      tended to be higher than those in group 2. CONCLUSIONS: The present survey
      demonstrated a negative impact of urinary incontinence on the psychological
      burden of family caregivers.

PMID- 19090590
TI  - Partial bladder outlet obstruction reduces the tissue antioxidant capacity and
      muscle nerve density of the guinea pig bladder.
AB  - AIMS: Reactive nitrogen and oxygen species (RNOS) likely play a role in the
      development of bladder dysfunction related to bladder outlet obstruction.
      Antioxidants protect against these free radicals. The aim of our study was to
      investigate the effect of bladder outlet obstruction on the endogenous
      antioxidant status of the bladder and to correlate this to bladder structure and
      function. METHODS: In 16 guinea pigs either a partial outlet obstruction or a
      sham operation was induced. The contractile responses of detrusor strips to
      electrical field stimulation (EFS), acetylcholine, potassium, and ATP were
      monitored 4 weeks after the operation. The nerve density in bladder tissue was
      determined by using the non-specific nerve marker PGP 9.5. Separate antioxidants
      and the total antioxidant status were assessed using the trolox equivalent
      antioxidant capacity (TEAC) test. RESULTS: Contractile responses of detrusor
      strips to EFS were for the greater part based on neurogenic stimulation. The
      nerve-mediated responses in strips from obstructed bladders were lower compared
      to the sham group. Obstructed bladders showed a patchy denervation and the nerve
      density was significantly lower compared to the sham group. The total antioxidant
      capacity, the glutathione and the glutathione reductase (GR) levels significantly
      decreased in obstructed bladders compared to the sham group. CONCLUSION: This
      study demonstrates that the antioxidant status of guinea pig bladders exposed to
      outlet obstruction decreased which might be associated with the observed
      reduction in nerve density. The results strengthen the hypothesis that oxidative
      stress is involved in the pathophysiology of bladder dysfunction related to
      obstructed bladders. Neurourol. Urodynam. 28:461-467, 2009. (c) 2008 Wiley-Liss,
      Inc.

PMID- 19090591
TI  - The number of voiding radiographs during cystourethrography in women with stress
      incontinence or prolapse can be reduced to enhance safety without compromising
      study interpretation.
AB  - AIM: Based on a prior study, over 60% of the average radiation dose per
      cystourethrography (CU) originated from lateral radiograph images (RI). This
      analysis focuses on the feasibility of decreasing the number of RI without
      compromising study interpretation. METHODS:  MATERIAL AND METHOD: Following IRB
      approval, all RIs from the initial study in women with incontinence and/or
      bladder prolapse were assessed at random for reading consistency (inter-rater
      reliability (IRR)) and reliability (intra-rater reliability (IaRR)) by four
      independent reviewers. Interpretation guidelines on urethral readability were
      established and 15 repeated RIs tested for IaRR. Two months later, the reviewers
      selected the best two RIs for each CU with the RI presented in a random order.
      RESULTS: From 88 CU exams providing 304 RIs, good IRRs for readability
      (kappa=0.82, ICC=0.80) and interpretation (kappa=0.60, ICC=0.57) were found
      between reviewers. Mean IaRR for readable versus unreadable categories was 87%
      and among readable images was 95% for interpretation. The RIs judged best had a
      high IRR (kappa=0.83, ICC=0.83) and were predominantly from the early and middle
      phases of the void. CONCLUSION: A high level of agreement was found for urethral
      readability and interpretation between reviewers of varying experience using pre
      established guidelines. No more than 3 RIs were required for study interpretation
      and those views were from the early to middle phase of voiding, thus allowing a
      radiation dose reduction without compromising the quality of the CU exam.
      Neurourol. Urodynam. 28:385-389, 2009. (c) 2008 Wiley-Liss, Inc.

PMID- 19090592
TI  - Quality control in urodynamics: Analysis of an international multi-center study.
AB  - AIMS: To review the quality of urodynamic traces collected as part of a multi
      center Phase II drug trial of a medication for overactive bladder (OAB), in order
      to assess adherence to the Good Urodynamic Practice (GUP) guidelines. To assess
      inter-rater reliability (IRR) for the numerical cystometrogram variables, and for
      the diagnosis of detrusor overactivity (DO). METHODS: Two central reviewers
      assessed 50 cystometrograms, recording the presence or absence of DO and
      assessing compliance with GUP guidelines. Three central reviewers independently
      assessed 20% of cystometrograms submitted, for numerical variables. IRR of
      central and peripheral assessments were compared with intra-class correlation
      (ICC) and Cohen's unweighted kappa statistics. RESULTS: There was inconsistent
      adherence to GUP guidelines, because of differences in urodynamic equipment and
      practice. ICC between numerical variables assessed by the three central reviewers
      were excellent ranging between 0.830 and 0.997 (P all < or =0.001). ICC between
      numerical variables assessed by peripheral and central reviewers were good to
      excellent, ranging between 0.624 and 0.994 (P all < or =0.05). Central reviewers
      showed excellent agreement in the assessment of DO (kappa = 0.83). However
      central and peripheral reviewers showed poor agreement in the assessment of DO
      (kappa = 0.24). CONCLUSION: Without standardization of equipment and training,
      adherence to GUP guidelines is problematic. Cystometric pressure and volume
      variables can however be reliably assessed in multi-center studies. DO cannot be
      reliably observed by interpreting the cystometrogram trace in isolation.
      Objective assessment of DO may therefore be unsuitable for multi-center studies
      reliant on central reporting of traces. Neurourol. Urodynam. 28:380-384, 2009.
      (c) 2008 Wiley-Liss, Inc.

PMID- 19090593
TI  - Observations relating to urinary sensation during detrusor overactivity.
AB  - AIMS: To describe the temporal relationship between increases in lower urinary
      tract (LUT) sensation and changes in detrusor and/or urethral pressures measured
      in real time. METHODS: We reviewed 33 multichannel urodynamic tracings that
      included a continuous recording of LUT sensation and that demonstrated detrusor
      overactivity incontinence (DOI) or detrusor overactivity (DO). Four physicians
      reviewed each urodynamic tracing and reached agreement about the temporal
      relationship between LUT sensation and detrusor contraction. RESULTS: Median age
      was 60 (36-82) years. Fourteen (42%) had urodynamic diagnoses of mixed
      incontinence, 18 (55%) had DOI, and 1 (3%) had DO without DOI. We reviewed 119
      episodes of detrusor overactivity from the 33 recordings. We found no difference
      in change in sensation level when comparing DO episodes with DOI episodes or
      between different urodynamic diagnoses (P > 0.5). There was no dominant temporal
      pattern seen for the whole group (P = 0.84), that is, there was no evidence that
      the change in sensation level was more likely to occur before, during, or after
      DO/DOI episodes. When evaluating the changes in the urethral pressure, the most
      common pattern seen was an increase in sensation level after a fall in urethral
      pressure, but no dominant pattern was seen. CONCLUSIONS: Our findings suggest
      that increased LUT sensation during DO/DOI is not reliably caused by measurable
      alterations in bladder or urethral pressure.

PMID- 19090594
TI  - The efficacy of a wetting alarm diaper for toilet training of young healthy
      children in a day-care center: a randomized control trial.
AB  - AIMS: To evaluate, in a randomized controlled way, the use of a daytime wetting
      alarm in a day-care center during three consecutive weeks in healthy children.
      METHODS: Thirty-nine healthy young children, between 18 and 30 months old, were
      selected at random for a wetting alarm diaper training (n = 27) or control
      wearing a placebo alarm (n = 12). Toilet behavior was observed during a period of
      10 hr by independent observers before, at the end of, and 2 weeks after training.
      Children were defined as completing daytime toilet training when the child wore
      undergarments, showed awareness of a need to void, initiated the toileting
      without prompts or reminder from the trainer and had maximum one leakage accident
      per day. RESULTS: Children in the wetting alarm diaper training group achieved
      independent bladder control in 51.9% and did significantly better than in the
      control group (8.3%) (P = 0.013). The results were sustained during the following
      14 days (P = 0.013). CONCLUSION: The wetting alarm diaper training is an
      effective option for toilet training young healthy children in a day-care center.
      It offers day-care providers clear guidelines and limits the time to complete
      toilet training in many children without putting too much burden on the child and
      the day-care center activities.

PMID- 19090595
TI  - "Society as an organism": metaphor as departure point of Andrija Stampar's health
      ideology.

PMID- 19090596
TI  - Setting priorities in global child health research investments: guidelines for
      implementation of CHNRI method.
AB  - This article provides detailed guidelines for the implementation of systematic
      method for setting priorities in health research investments that was recently
      developed by Child Health and Nutrition Research Initiative (CHNRI). The target
      audience for the proposed method are international agencies, large research
      funding donors, and national governments and policy-makers. The process has the
      following steps: (i) selecting the managers of the process; (ii) specifying the
      context and risk management preferences; (iii) discussing criteria for setting
      health research priorities; (iv) choosing a limited set of the most useful and
      important criteria; (v) developing means to assess the likelihood that proposed
      health research options will satisfy the selected criteria; (vi) systematic
      listing of a large number of proposed health research options; (vii) pre-scoring
      check of all competing health research options; (viii) scoring of health research
      options using the chosen set of criteria; (ix) calculating intermediate scores
      for each health research option; (x) obtaining further input from the
      stakeholders; (xi) adjusting intermediate scores taking into account the values
      of stakeholders; (xii) calculating overall priority scores and assigning ranks;
      (xiii) performing an analysis of agreement between the scorers; (xiv) linking
      computed research priority scores with investment decisions; (xv) feedback and
      revision. The CHNRI method is a flexible process that enables prioritizing health
      research investments at any level: institutional, regional, national,
      international, or global.

PMID- 19090597
TI  - Factors associated with fatal traffic accidents in Tirana, Albania: cross
      sectional study.
AB  - AIM: To assess the prevalence of fatal road traffic accidents in Tirana, Albania,
      and describe their determinants. METHODS: This cross-sectional study included all
      road traffic accidents recorded by the Traffic Police Department of Tirana
      district for the period 2000-2005. A structured questionnaire included
      information about the type of traffic accident (fatal vs non-fatal event), year
      of event, age and sex of the responsible party, reason of accident, location and
      time of event, and the type of vehicle involved. Multivariable-adjusted binary
      logistic regression analysis was used to assess the predictors of fatal road
      traffic accidents. RESULTS: Overall, there were 1578 recorded road traffic
      accidents in Tirana district during 2000-2005. Of these, 272 (17%) were fatal.
      Multivariable-adjusted models showed that younger age (OR, 3.97; 95% CI, 2.28
      6.91), high speed (OR, 2.54; 95% CI, 1.62-3.98), and especially alcohol
      consumption (OR, 6.15; 95% CI, 3.54-10.66) were strong and significant predictors
      of fatal accidents. Fatal accidents were more prevalent on intercity roads (OR,
      4.25; 95% CI, 3.11-5.82) and involved especially vans and trucks (OR, 4.12; 95%
      CI, 2.34-7.24). CONCLUSION: Young age, high speed, and alcohol are predictors of
      fatal road traffic accidents in Tirana district. These findings can serve as a
      basis for health care professionals and policymakers to create preventive
      measures for traffic accidents.

PMID- 19090598
TI  - Prevalence and correlates of asthma among children in central St. Petersburg,
      Russia: cross-sectional study.
AB  - AIM: To estimate the prevalence of asthma among children in central St.
      Petersburg and to evaluate associations between asthma and socio-demographic,
      biological, and environmental factors. METHODS: A cross-sectional study included
      1464 children aged 0-18 years from two central districts of St. Petersburg.
      Parents filled out a questionnaire on children's respiratory health,
      characteristics at birth, socio-demographic data, housing situation, and their
      own history of asthma and allergies. The diagnosis of asthma was based on the
      results of spirometry in children aged > or =5 years and on questionnaire data as
      reported by parents of younger children. Independent effects of the investigated
      factors on asthma were assessed by multiple logistic regression analysis. Crude
      and adjusted odds ratios (OR) with 95% confidence intervals (CI) were calculated.
      RESULTS: The estimated prevalence of asthma was 7.4% (95% CI, 6.2-8.8). A history
      of allergies (OR, 1.6; 95% CI, 1.0-2.6), bronchitis, bronchiolitis, or pneumonia
      in infancy (OR, 12.2; 95% CI, 7.3-20.5), and self-reported parental allergies
      (OR, 3.6; 95% CI, 2.2-5.8 for one parent and OR, 7.1; 95% CI, 3.0-17.0 for both
      parents) were associated with childhood asthma. Children whose mothers were out
      of work also had higher prevalence of asthma than the reference group (OR, 3.4;
      95% CI, 1.1-10.4). CONCLUSION: The prevalence of asthma is several times higher
      than what is officially reported for St. Petersburg's inner city children
      population. Early life events and socio-demographic and biologic factors were
      associated with asthma in children.

PMID- 19090599
TI  - Partner's smoking status and acute coronary syndrome: population-based case
      control study in Tirana, Albania.
AB  - AIM: To assess the association between partners' smoking status and acute
      coronary syndrome in never smokers in Albania. METHODS: This population-based
      case-control study was conducted in Tirana in the period 2003-2006. It involved
      467 consecutive patients with non-fatal acute coronary syndrome and 737 controls.
      Only married never-smokers (169 patients with acute coronary syndrome and 323
      controls) were included in the analysis. Information on socioeconomic status,
      coronary risk factors, and partners' current smoking status was obtained by a
      structured questionnaire. Multivariate logistic regression was used to assess the
      association between partner's smoking status and acute coronary syndrome.
      RESULTS: Among patients with acute coronary syndrome, 49% of women and 25% of men
      had a partner who was a current smoker, as opposed to 44% of women and 16% of men
      in the control group. In age-adjusted models, non-smoking men with smoking
      partners had a greater acute coronary syndrome risk (odds ratio [OR], 1.76; 95%
      confidence interval [CI], 0.98-3.18), while no association was found in women
      with smoking partners (OR, 1.05; 95% CI, 0.48-2.30). After adjustment for
      socioeconomic characteristics, coronary risk factors, and psychosocial factors,
      the acute coronary syndrome risk in men was somewhat lower (1.68; 95% CI, 0.81
      3.47), while for women it was somewhat greater but still non-significant (1.19;
      95% CI, 0.25-5.64). Sex-pooled estimate of the risk was OR 1.64 (95% CI, 0.96
      2.83). CONCLUSION: Partner's current smoking status was positively associated
      with a greater acute coronary syndrome risk in men but not in women, both before
      and after adjustment for socioeconomic characteristics and coronary risk factors.
      Programs aimed at reducing the exposure to passive smoking are need in countries
      with high prevalence of active smoking.

PMID- 19090600
TI  - Medical audit of diabetes mellitus in primary care setting in Bosnia and
      Herzegovina.
AB  - AIM: To assess the quality of diabetes care provided by family medicine teams in
      primary health centers in Bosnia and Herzegovina (BH) through a medical audit,
      addressing the extent to which clinical practice complied with pre-determined
      explicit criteria of long-term management. METHOD: Retrospective analysis
      included randomly selected medical records of patients with type 1 or 2 diabetes
      mellitus treated by 18 family medicine teams at 5 locations in BH, included in
      the Canadian International Development Agency/World Health Organization project
      "Strengthening health care systems in BH with focus on primary health care/family
      medicine model." Audit record form contained 24 questions on sex, age, diabetes
      type, body mass index (BMI), hypertension, family anamnesis, annual examinations
      (HbA1C, BMI, lipid profile or total cholesterol, blood creatinine, neurological
      examination, urinalysis for albuminuria, foot care, and examination of ocular
      fundus), smoking habits, alcohol consumption, patient education, prescribed
      insulin and other drugs, and patient's health care-seeking behavior. Standardized
      and record forms were returned anonymously with 99.3% response rate. RESULTS:
      Records of 536 patients with diabetes were analyzed (64% women and 87% patients
      with diabetes mellitus type 2). Family medicine teams showed poor compliance with
      established criteria for diabetes control. Metabolic control (69.5%) was
      acceptable, but the level of monitoring complications of diabetes (foot and
      ocular fundus examined in 53.4% and 53% of patients, respectively) was low. There
      were also considerable variations in diabetes management between different
      centers as well as between the teams in the same center. CONCLUSION: The audit
      revealed deficiencies in the quality of diabetes care and variations in care
      provision between primary care teams. Clinical guidelines and continuing
      education about acceptable diabetes care should be developed and implemented in
      BH.

PMID- 19090601
TI  - Long-term abstinence and well-being of alcohol-dependent patients after intensive
      treatment and aftercare telephone contacts.
AB  - AIM: To identify whether intensive treatment and aftercare telephone contacts
      influence long-term abstinence and well-being of patients with alcohol
      dependency. METHODS: Six hundred and twenty two patients were evaluated at the
      beginning and end of intensive in-patient treatment. At the end of the treatment,
      the patients were divided into two recruitment cohorts--telephone contact group
      (n=347), in whom basic outcome criteria (abstinence, marital and employment
      status, self-evaluation of well-being) were evaluated 3, 6, 12, and 24 months
      after intensive treatment, and no contact group (n=275) in whom the basic outcome
      criteria were checked only at 24 months after the intensive treatment. At 24
      months, response rate was 33.4% in telephone contact group (n=116) and 30.5%
      (n=84) in no contact group. RESULTS: Positive indicators of therapy success
      (abstinence or decrease in drinking, stabile social relations, and more positive
      self-evaluation of well-being) were found in 53.0% of patients at 3 months, 44.3%
      at 6 months, and 30.6% at 12 months in telephone contact group. Overall
      abstinence 24 months after the end of intensive treatment was reported in 25.7%
      of all patients, including non-respondents. Both groups achieved significant
      improvement in subjective well-being during intensive treatment. At 24 months, 3
      attributes of subjective well-being (subjective psychological health, evaluation
      of financial status, general quality of life) were significantly higher in
      telephone contact group. However, groups did not significantly differ in the
      abstinence level (telephone contact group=27.7%, no contact group=24.4%).
      CONCLUSION: Significant differences in well-being variables between telephone
      contact group and no contact group at 24 months after the end of intensive
      treatment are at least partially due to phone contact/informative checking 3, 6,
      and 12 months after the end of intensive therapy. Telephone or any short and easy
      accessible communication checking is a promising as supportive and research tool
      in aftercare alcohol addiction treatment, especially because of its cost-benefit
      advantages.

PMID- 19090603
TI  - Cardiovascular risk assessment of Bulgarian urban population: cross-sectional
      study.
AB  - AIM: To assess the total cardiovascular risk of the Bulgarian urban population.
      METHODS: A representative sample of Bulgarian urban population (n=3810, response
      rate 68.3%) from five Bulgarian cities was included in a cross-sectional
      observation study performed in the period 2005-2007. A detailed cardiovascular
      risk assessment was performed by general practitioners and a total 10-year risk
      of a fatal cardiovascular event was estimated according to the European
      Systematic Coronary Risk Evaluation (SCORE, HeartScore. RESULTS: There were 48.7%
      of participants in the high risk group (SCORE > or =5%), 24.3% aged 45-54 and
      more than half aged 55-64 years. Nearly a quarter of the sample had a total
      cardiovascular risk of over 10% (SCORE > or =10%), whereas 10.1% of the sample
      had excessively high cardiovascular risk (SCORE > or =15%). In the 65-75 age
      group, the prevalence of men with excessively high risk was 46.6%, compared with
      6.0% in women (P<0.001). Most of the main cardiovascular risk factors were
      slightly increased or borderline in comparison with clinical thresholds.
      CONCLUSIONS: Cardiovascular risk is high in a large proportion of Bulgarian urban
      population, especially in men aged over 65. These findings indicate that a
      comprehensive national strategy and program for management of cardiovascular
      diseases is urgently needed. The SCORE method can be well implemented if a higher
      threshold for a high risk group is defined and smaller target population is
      planned for extensive and expensive high risk preventive measures.

PMID- 19090602
TI  - Comparable postprandial glucose reductions with viscous fiber blend enriched
      biscuits in healthy subjects and patients with diabetes mellitus: acute
      randomized controlled clinical trial.
AB  - AIM: To compare the blood glucose-lowering effect of a highly viscous fiber blend
      (VFB) added to a starchy snack on postprandial glycemia between healthy
      participants and participants with diabetes mellitus. METHODS: Ten healthy
      participants (4 men and 6 women, aged 28+/-2.6 years, body mass index [BMI],
      24.3+/-0.8 kg/m(2)) and 9 participants with diabetes mellitus type 2 (3 men and 6
      women, aged 68+/-3.8 years, BMI 28.8+/-1.2 kg/m(2)) on four separate occasions
      took either 50 g available carbohydrates as control biscuits, biscuits with 10 g
      of highly viscous fiber blend, white bread with 12 g of margarine, or white bread
      alone. Postprandial blood glucose response, glycemic index (GI), and palatability
      were determined. RESULTS: Mean (95% confidence interval) GI values of the viscous
      fiber blend biscuits were 26 (16-36) and 37 (27-47) GI units for healthy
      participants and participants with diabetes mellitus, respectively. These values
      were significantly lower than those of white bread, white bread with 12 g of
      margarine, and control biscuits (P<0.001, paired t test) both in healthy
      participants (GI 100, 108 [57-159], and 101 [44-158], respectively) and
      participants with diabetes mellitus (GI 100, 103 [79-127], and 94 [78-110],
      respectively). Viscous fiber blend significantly reduced the glycemic index by
      74% (7.4 GI units/g of fiber) in healthy participants and by 63% (6.3 GI units/g
      of fiber) in participants with diabetes. The GI did not differ between control
      meals in both healthy participants and participants with diabetes. There were no
      significant differences in palatability among the types of meals, although
      participants with diabetes found the viscous fiber blend biscuits more palatable
      (P=0.002, t test). CONCLUSION: Viscous fiber blend is a very potent and palatable
      soluble fiber addition to a starchy snack, which is able to reduce the glycemic
      response to a similar extent in both healthy participants and individuals with
      diabetes mellitus. Biscuits with low GI, and possibly other viscous fiber blend
      fortified starchy foods, may potentially be a useful replacement of high GI snack
      foods in the diet.

PMID- 19090604
TI  - Cancer mortality among men in Central Serbia: 1985-2006 survey study.
AB  - AIM: To analyze cancer mortality trends in men in Central Serbia during 1985-2006
      period. METHODS: Mortality rates and trends for the most frequent cancers in men
      (lung, stomach, colorectal, pancreatic, and prostate cancer) were calculated.
      Mortality rates for all cancers were adjusted by direct standardization.
      Percentage changes of the rates were calculated as the percentage difference
      between the rates of two successive years and then as a mean of these changes for
      the entire observed period. Trend lines were estimated using linear regression.
      RESULTS: Total cancer mortality in men increased, with mean percentage of annual
      changes being 1.53% (95% confidence interval [CI], -0.09-3.16). Lung, stomach,
      colorectal, pancreatic, and prostate cancers represented 58.1% and 61.6% of total
      cancer deaths in 1985 and 2006, respectively. Increasing trends were observed for
      all investigated cancers: mean annual percentage change for lung cancer was
      2.31%(95% CI, 1.03-3.59), for colorectal cancer 2.23% (95% CI, -0.18-4.65), for
      prostate cancer 3.06% (95% CI, -2.07-8.18), and for pancreatic cancer 1.58% (95%
      CI, -2.17-5.32). Stomach cancer mortality significantly decreased in age groups
      40-49 and 50-59 years. CONCLUSION: The most frequent cancers in men in Central
      Serbia, i.e., lung, colorectal, prostate, and pancreatic cancer, showed an
      increasing trend. Only stomach cancer mortality decreased over time.

PMID- 19090605
TI  - Perceived difficulties in managing ethical problems in family practice in
      Slovenia: cross-sectional study.
AB  - AIM: To determine the prevalence of difficulties in managing ethical dilemmas in
      family practice. METHODS: The study included a random sample of 259 family
      medicine physicians, representing 30% of the population of family physicians in
      Slovenia. Participants were given a self-administered questionnaire on perceived
      ethical dilemmas in their practice, with responses on a 5-point scale and a
      maximum score of 100. The main outcome measure was the percentage of family
      physicians reporting difficulties in solving perceived ethical dilemmas. RESULTS:
      The response rate was 55%. Physicians reported having difficulties in solving
      ethical dilemmas often or very often (mean score+/-standard deviation, 56.1+/
      12.1). The most difficult ethical issue included abandoned and unattended
      patients and patients with insufficient means of support (48.6%), followed by
      suspicion of physical abuse, sexual abuse, or other criminal behavior (40.9%),
      and use of limited health care resources (21.1%). Female physicians reported
      greater difficulties in solving ethical dilemmas than male physicians (57.7+/
      10.6 vs 53.0+/-14.1, P=0.036, t test). Older physicians solved ethical issues
      more easily than younger ones (53.9+/-12.6 vs 58.2+/-11.2, P=0.043, t test).
      Specialists and residents in family medicine considered solving ethical dilemmas
      to be more difficult than general practitioners without specialization (57.3+/
      11.6 vs 47.1+/-11.8, P=0.001, t test). Multivariate regression analysis of
      physician and practice characteristics did not yield any significant model to
      explain the differences in the perceived level of difficulties in solving ethical
      dilemmas. CONCLUSION: Although managing ethical dilemmas is an important part of
      daily work of family physicians in Slovenia, it is perceived as a considerable
      burden in their work. Family physicians need more training in addressing and
      managing ethical issues.

PMID- 19090606
TI  - Tuberculosis incidence in elderly in Serbia: key trends in socioeconomic
      transition.
AB  - AIM: To examine tuberculosis incidence rates among the elderly in Central Serbia
      in 1992-2006 period, which was characterized by socioeconomic crisis and
      migration of population. METHODS: We analyzed all reported active tuberculosis
      cases in a 15-year period, especially among patients aged > or =65, according to
      the Annual Reports of the Institute of Lung Diseases and Tuberculosis in Belgrade
      and Central Tuberculosis Register. Population estimates with extrapolations were
      based on 1991 and 2002 census data. RESULTS: Total tuberculosis incidence rates
      showed a slight but non-significant decreasing trend (P=0.535), and no
      significant increase was found in patients aged > or =65 years (P=0.064), with an
      average age-specific incidence rate for the elderly of 64.0 (95% confidence
      interval, 60.7-67.4). The increase was significant in patients aged > or =70
      years (y=49.3549+2.1186x; P=0.001), both in men (y=62.8666+2.3977x; P=0.005) and
      even more prominently in women (y=39.8240+1.9150x; P<0.001). The proportion of
      tuberculosis cases in the elderly peaked in 2005, with 35% of all tuberculosis
      cases. CONCLUSION: High incidence rates and increasing time trend of tuberculosis
      in the elderly in Central Serbia is a serious problem, especially among those
      aged 70 years and over, who might present a target group for active case-finding
      of the disease.

PMID- 19090607
TI  - Patient, physician, and practice characteristics related to patient enablement in
      general practice in Croatia: cross-sectional survey study.
AB  - AIM: To investigate the quality of general practice care in Croatia by using
      patient enablement as a consultation outcome measure and its association with
      patient, physician, and practice characteristics. METHODS: A cross-sectional
      questionnaire-based study performed from November 2003 to March 2004 included a
      national stratified random sample of 350 general practitioners, who were asked to
      collect data on 50 consecutive consultations with their patients aged > or =18
      years. Patients provided data on patient enablement (Patient Enablement
      Instrument, score range 0-12), consultation length, sociodemographic data, how
      well they knew the physician, health self-assessment, quality of life, and reason
      for the visit. Physicians provided data on age, sex, vocational training, working
      experience, educational work, average number of patients per day, and type of
      practice. RESULTS: In 5527 patients, the mean score (+/-standard deviation) for
      enablement at consultation was 6.6+/-3.3 and the mean consultation length was
      11.5+/-5.5 minutes. Logistic regression analysis showed that lack of continuity
      of care (men: OR, 0.56; 95% CI, 0.47-0.67; women: OR, 0.52; 95% CI, 0.45-0.61),
      poor self-perceived health (men: OR, 1.76; 95% CI, 1.49-2.07; women: OR, 1.77;
      95% CI, 1.53-2.04), low educational level, low quality of life for both sexes and
      older age in male patients predicted low enablement (P<0.05 for each). Physician
      age, sex, and average number of patients per day were significantly correlated
      with enablement for male patients and physician working experience with
      enablement for female patients (P<0.05 for each). CONCLUSION: Patient enablement
      score in Croatia is high in comparison with countries such as the UK and Poland.
      Enablement at consultations was related to the continuity of care and patient
      health status, and other patient, physician, and practice characteristics,
      suggesting that these parameters should be considered when assessing quality of
      care in general practice.

PMID- 19090608
TI  - Association of socioeconomic status measured by education and risk factors for
      carotid atherosclerosis: cross-sectional study.
AB  - AIM: To investigate the association between socioeconomic status and metabolic
      syndrome, lifestyle, clinical and biochemical characteristics, and inflammatory
      markers as risk factors for carotid atherosclerotic disease. METHODS: This cross
      sectional study, involving 657 consecutive patients with verified carotid
      atherosclerotic disease, was performed in Belgrade, Serbia, during the period
      2006-2007. Formal education level was used as a proxy for socioeconomic status.
      Anthropometric parameters and data on cardiovascular risk factors were analyzed
      in participants with different levels of education--low (< or = primary school),
      medium (secondary school), and high (university education). In the analysis,
      univariate and multivariate logistic regressions were used. RESULTS: Multivariate
      analysis showed that low education was significantly positively associated with
      female sex (odds ratio [OR], 2.38; 95% confidence interval [CI], 1.45-3.81),
      increased triglycerides (OR, 1.79; 95% CI, 1.12-2.78), increased high-sensitivity
      C-reactive protein (hsCRP) (OR, 3.53; 95% CI, 2.17-5.88), and physical inactivity
      (OR, 4.24; 95% CI, 1.82-9.86) and negatively associated with former smoking (OR,
      0.42; 95% CI, 0.23-0.75). Medium education was significantly positively
      associated with increased triglycerides (OR, 1.73; 95% CI, 1.14-2.62) and
      increased hsCRP (OR, 2.17; 95% CI, 1.37-3.41), and negatively with age (OR, 0.97;
      95% CI, 0.94-0.99). CONCLUSION: Increased triglycerides and hsCRP in people with
      low and medium education, and high prevalence of metabolic syndrome, its
      components and inflammatory markers in all study participants, suggest that
      regular health check-up, especially for those with lower education, may be useful
      in early detection and treatment of any abnormality that can be associated with
      cardiovascular disease.

PMID- 19090609
TI  - Prevalence of chronic diseases according to socioeconomic status measured by
      wealth index: health survey in Serbia.
AB  - AIM: To examine socioeconomic inequalities in the prevalence of chronic diseases
      in Serbia, using the data from 2006 national health survey. METHOD: A stratified
      sample of 7673 households was selected and 14522 household members older than 20
      years were interviewed (response rate 80.5%). Wealth index was used as a measure
      of socioeconomic status. Standardized morbidity prevalence ratios were computed
      using the poorest category as reference. Odds ratios for the prevalence of the
      selected chronic diseases and their 95% confidence intervals were calculated by
      multivariate logistic analysis adjusted for age, education, smoking status, and
      body mass index. RESULTS: Hypertension was the most prevalent disease in all
      socioeconomic categories; standardized morbidity prevalence ratios were higher in
      richer men (151.3 in the richest) and lower in richer women (86.1 in the
      richest). Rheumatism/arthritis was the second most prevalent disease in both
      sexes, with the highest prevalence in the poorest group; the pattern remained the
      same after standardization (standardized morbidity prevalence ratio in the
      richest: 86.4 in men and 74.0 in women). The prevalence of hyperlipidemia was
      associated with wealth index in both men and women and was highest in the richest
      group; the pattern remained the same after standardization (standardized
      morbidity prevalence ratio in the richest: 275.9 in men and 138.4 in women).
      Logistic regression models showed that higher wealth index was associated with
      higher prevalence of hypertension, hyperlipidemia, and allergy, while lower
      wealth index was associated with higher prevalence of rheumatism/arthritis.
      CONCLUSION: There were considerable socioeconomic inequalities in the prevalence
      of chronic diseases in Serbia. These results indicate an opportunity to reduce
      inequalities and show a need for further investigation on the determinants of
      chronic diseases.

PMID- 19090611
TI  - Language as vehicle for spread and prevention of HIV in Malawi.

PMID- 19090610
TI  - Ability to work and employability of patients in opioid substitution treatment
      programs in Slovenia.
AB  - AIM: To assess the ability to work and employability of individuals taking part
      in opioid substitution treatment programs (OSTP). METHODS: The study was composed
      of two surveys. In the first survey, 237 of 480 patients enrolled in OSTP
      responded to the questionnaire about their employment status, opinion about
      employment, and perception of assignments before and during OSTP. In the second
      survey, 66 of 100 employers responded to the questionnaire on the occurrence,
      perception, and management of addiction problems in their companies. RESULTS:
      Unemployment rate in individuals enrolled in OSTP was 43.5% and decreased during
      OSTP by 10.5% (P=0.027). Irregular use of OSTP medications was the most important
      factor for unemployment (odds ratio, 2.44; P=0.016). OSTP was highly effective in
      achieving a positive change in patients' perception of different kinds of
      assignments previously perceived as beyond their abilities. Thus, perception of
      mentally demanding assignments (P<0.001), working at unfavorable hours (P<0.001),
      and forced work pace (P<0.001) represented much lower burden after entering OSTP.
      Only 6.6% of employers reported illicit drugs as being a problem at their
      companies and 79.1% believed they would not recognize a person under the
      influence of illicit drugs. In 93.0% of the cases, applicants for a job would
      have had lower chances if they had been drug users; the percentage was slightly
      higher for those taking part in OSTP (94.7%). CONCLUSION: OSTP in Slovenia was
      effective in increasing both employability and OSTP patients' ability to work. To
      facilitate complete rehabilitation, particularly in obtaining employment for the
      patients, the process must involve the society as a whole.

PMID- 19090612
TI  - Public health or pubic health: is there a difference?

PMID- 19090613
TI  - Take a look inside your eye.

PMID- 19090614
TI  - A case-control study to assess the relationship between poverty and visual
      impairment from cataract in Kenya, the Philippines, and Bangladesh.
AB  - BACKGROUND: The link between poverty and health is central to the Millennium
      Development Goals (MDGs). Poverty can be both a cause and consequence of poor
      health, but there are few epidemiological studies exploring this complex
      relationship. The aim of this study was to examine the association between visual
      impairment from cataract and poverty in adults in Kenya, Bangladesh, and the
      Philippines. METHODS AND FINDINGS: A population-based case-control study was
      conducted in three countries during 2005-2006. Cases were persons aged 50 y or
      older and visually impaired due to cataract (visual acuity < 6/24 in the better
      eye). Controls were persons age- and sex-matched to the case participants with
      normal vision selected from the same cluster. Household expenditure was assessed
      through the collection of detailed consumption data, and asset ownership and self
      rated wealth were also measured. In total, 596 cases and 535 controls were
      included in these analyses (Kenya 142 cases, 75 controls; Bangladesh 216 cases,
      279 controls; Philippines 238 cases, 180 controls). Case participants were more
      likely to be in the lowest quartile of per capita expenditure (PCE) compared to
      controls in Kenya (odds ratio = 2.3, 95% confidence interval 0.9-5.5), Bangladesh
      (1.9, 1.1-3.2), and the Philippines (3.1, 1.7-5.7), and there was significant
      dose-response relationship across quartiles of PCE. These associations persisted
      after adjustment for self-rated health and social support indicators. A similar
      pattern was observed for the relationship between cataract visual impairment with
      asset ownership and self-rated wealth. There was no consistent pattern of
      association between PCE and level of visual impairment due to cataract, sex, or
      age among the three countries. CONCLUSIONS: Our data show that people with visual
      impairment due to cataract were poorer than those with normal sight in all three
      low-income countries studied. The MDGs are committed to the eradication of
      extreme poverty and provision of health care to poor people, and this study
      highlights the need for increased provision of cataract surgery to poor people,
      as they are particularly vulnerable to visual impairment from cataract.

PMID- 19090615
TI  - Poverty and cataract--a deeper look at a complex issue.

PMID- 19090616
TI  - The dirty war index: statistical issues, feasibility, and interpretation.

PMID- 19090617
TI  - A new tool for measuring the brutality of war.

PMID- 19090618
TI  - Root system architecture from coupling cell shape to auxin transport.
AB  - Lateral organ position along roots and shoots largely determines plant
      architecture, and depends on auxin distribution patterns. Determination of the
      underlying patterning mechanisms has hitherto been complicated because they
      operate during growth and division. Here, we show by experiments and
      computational modeling that curvature of the Arabidopsis root influences cell
      sizes, which, together with tissue properties that determine auxin transport,
      induces higher auxin levels in the pericycle cells on the outside of the curve.
      The abundance and position of the auxin transporters restricts this response to
      the zone competent for lateral root formation. The auxin import facilitator,
      AUX1, is up-regulated by auxin, resulting in additional local auxin import, thus
      creating a new auxin maximum that triggers organ formation. Longitudinal spacing
      of lateral roots is modulated by PIN proteins that promote auxin efflux, and
      pin2,3,7 triple mutants show impaired lateral inhibition. Thus, lateral root
      patterning combines a trigger, such as cell size difference due to bending, with
      a self-organizing system that mediates alterations in auxin transport.

PMID- 19090619
TI  - SUMO-specific protease 2 is essential for modulating p53-Mdm2 in development of
      trophoblast stem cell niches and lineages.
AB  - SUMO-specific protease 2 (SENP2) modifies proteins by removing SUMO from its
      substrates. Although SUMO-specific proteases are known to reverse sumoylation in
      many defined systems, their importance in mammalian development and pathogenesis
      remains largely elusive. Here we report that SENP2 is highly expressed in
      trophoblast cells that are required for placentation. Targeted disruption of
      SENP2 in mice reveals its essential role in development of all three trophoblast
      layers. The mutation causes a deficiency in cell cycle progression. SENP2 has a
      specific role in the G-S transition, which is required for mitotic and
      endoreduplication cell cycles in trophoblast proliferation and differentiation,
      respectively. SENP2 ablation disturbs the p53-Mdm2 pathway, affecting the
      expansion of trophoblast progenitors and their maturation. Reintroducing SENP2
      into the mutants can reduce the sumoylation of Mdm2, diminish the p53 level and
      promote trophoblast development. Furthermore, downregulation of p53 alleviates
      the SENP2-null phenotypes and stimulation of p53 causes abnormalities in
      trophoblast proliferation and differentiation, resembling those of the SENP2
      mutants. Our data reveal a key genetic pathway, SENP2-Mdm2-p53, underlying
      trophoblast lineage development, suggesting its pivotal role in cell cycle
      progression of mitosis and endoreduplication.

PMID- 19090620
TI  - High functional diversity in Mycobacterium tuberculosis driven by genetic drift
      and human demography.
AB  - Mycobacterium tuberculosis infects one third of the human world population and
      kills someone every 15 seconds. For more than a century, scientists and
      clinicians have been distinguishing between the human- and animal-adapted members
      of the M. tuberculosis complex (MTBC). However, all human-adapted strains of MTBC
      have traditionally been considered to be essentially identical. We surveyed
      sequence diversity within a global collection of strains belonging to MTBC using
      seven megabase pairs of DNA sequence data. We show that the members of MTBC
      affecting humans are more genetically diverse than generally assumed, and that
      this diversity can be linked to human demographic and migratory events. We
      further demonstrate that these organisms are under extremely reduced purifying
      selection and that, as a result of increased genetic drift, much of this genetic
      diversity is likely to have functional consequences. Our findings suggest that
      the current increases in human population, urbanization, and global travel,
      combined with the population genetic characteristics of M. tuberculosis described
      here, could contribute to the emergence and spread of drug-resistant
      tuberculosis.

PMID- 19090621
TI  - Twist-2 controls myeloid lineage development and function.
AB  - Basic helix-loop-helix (bHLH) transcription factors play critical roles in
      lymphoid and erythroid development; however, little is known about their role in
      myeloid lineage development. In this study, we identify the bHLH transcription
      factor Twist-2 as a key negative regulator of myeloid lineage development, as
      manifested by marked increases in mature myeloid populations of macrophages,
      neutrophils, and basophils in Twist-2-deficient mice. Mechanistic studies
      demonstrate that Twist-2 inhibits the proliferation as well as differentiation of
      granulocyte macrophage progenitors (GMP) by interacting with and inhibiting the
      transcription factors Runx1 and C/EBPalpha. Moreover, Twist-2 was found to have a
      contrasting effect on cytokine production: inhibiting the production of
      proinflammatory cytokines such as interleukin-12 (IL-12) and interferon-gamma
      (IFNgamma) while promoting the regulatory cytokine IL-10 by myeloid cells. The
      data from further analyses suggest that Twist-2 activates the transcription
      factor c-Maf, leading to IL-10 expression. In addition, Twist-2 was found to be
      essential for endotoxin tolerance. Thus, this study reveals the critical role of
      Twist-2 in regulating the development of myeloid lineages, as well as the
      function and inflammatory responses of mature myeloid cells.

PMID- 19090622
TI  - The communication factor EDF and the toxin-antitoxin module mazEF determine the
      mode of action of antibiotics.
AB  - It was recently reported that the production of Reactive Oxygen Species (ROS) is
      a common mechanism of cell death induced by bactericidal antibiotics. Here we
      show that triggering the Escherichia coli chromosomal toxin-antitoxin system
      mazEF is an additional determinant in the mode of action of some antibiotics. We
      treated E. coli cultures by antibiotics belonging to one of two groups: (i)
      Inhibitors of transcription and/or translation, and (ii) DNA damaging. We found
      that antibiotics of both groups caused: (i) mazEF-mediated cell death, and (ii)
      the production of ROS through MazF action. However, only antibiotics of the first
      group caused mazEF-mediated cell death that is ROS-dependent, whereas those of
      the second group caused mazEF-mediated cell death by an ROS-independent pathway.
      Furthermore, our results showed that the mode of action of antibiotics was
      determined by the ability of E. coli cells to communicate through the signaling
      molecule Extracellular Death Factor (EDF) participating in mazEF induction.

PMID- 19090623
TI  - The role of auxin transport in plant patterning mechanisms.

PMID- 19090624
TI  - Timing precision in population coding of natural scenes in the early visual
      system.
AB  - The timing of spiking activity across neurons is a fundamental aspect of the
      neural population code. Individual neurons in the retina, thalamus, and cortex
      can have very precise and repeatable responses but exhibit degraded temporal
      precision in response to suboptimal stimuli. To investigate the functional
      implications for neural populations in natural conditions, we recorded in vivo
      the simultaneous responses, to movies of natural scenes, of multiple thalamic
      neurons likely converging to a common neuronal target in primary visual cortex.
      We show that the response of individual neurons is less precise at lower
      contrast, but that spike timing precision across neurons is relatively
      insensitive to global changes in visual contrast. Overall, spike timing precision
      within and across cells is on the order of 10 ms. Since closely timed spikes are
      more efficient in inducing a spike in downstream cortical neurons, and since fine
      temporal precision is necessary to represent the more slowly varying natural
      environment, we argue that preserving relative spike timing at a approximately 10
      ms resolution is a crucial property of the neural code entering cortex.

PMID- 19090625
TI  - Endoluminal stent-graft placement for repair of abdominal aortic aneurysms in the
      community setting.
AB  - PURPOSE: To demonstrate that results similar to high-volume academic centers can
      be achieved in the community setting when treating abdominal aortic aneurysm
      (AAA) using endovascular techniques, given appropriate volume and skill sets.
      METHODS: A retrospective review was conducted of 342 consecutive patients who
      underwent endovascular aneurysm repair (EVAR) by surgeons in a community hospital
      group from October 1999 through September 2005. In this population, 245 (71.6%)
      patients were treated with EVAR and 97 (28.4%) with open surgical repair. Of the
      245 EVAR patients (203 men; mean age 73.4+/-9.2 years), 218 AneuRx, 19 Ancure, 6
      Excluder, and 2 Zenith stent-grafts were implanted by 2 vascular surgeons to
      exclude AAAs with a mean diameter of 54+/-11 mm. Patients were followed
      postoperatively with office visits and computed tomography at 1, 6, and 12 months
      and annually thereafter. RESULTS: Technical success was achieved in 99.6%
      (244/245) with 1 intraoperative conversion. Mean operative time was 131+/-57
      minutes, with a mean contrast load of 161.6+/-65.5 mL. Thirty-five (14.3%)
      patients required intraoperative blood transfusion. Length of stay was 2.3+/-4.5
      days. Thirty-day mortality was 0.8% (2/245). Secondary procedures were required
      in 15 (6.1%) patients. Kaplan-Meier estimates of freedom from secondary
      interventions were 98%, 98%, 95%, and 90% at 12, 24, 36, and 48 months,
      respectively. At the same time points, freedom from surgical conversion was 99%,
      99%, 97%, and 96%, and freedom from aneurysm-related death was 97%, 96%, 96%, and
      96%. CONCLUSION: Endovascular AAA repair provides a less invasive method of
      managing aortic disease with resultant low perioperative mortality. Results in
      our community hospital demonstrate that this technology can be applied outside an
      academic environment in nearly three quarters of the population with excellent
      short and long-term results.

PMID- 19090626
TI  - Symptomatic aneurysm rupture without bleeding secondary to endotension 4 years
      after endovascular repair of an abdominal aortic aneurysm.
AB  - PURPOSE: To demonstrate the absence of bleeding from a ruptured abdominal aortic
      aneurysm (AAA) without evidence of endoleak following endovascular aneurysm
      repair (EVAR). CASE REPORT: A 72-year-old woman developed aneurysm enlargement 4
      years after EVAR of an infrarenal AAA. During surgical exploration for abdominal
      pain and presumed aneurysm rupture, the ruptured aneurysm sac was found to be
      filled with gelatinous material without evidence of thrombus or active bleeding.
      CONCLUSION: This case provides insight into the natural history of endotension
      and indicates that conservative management even in the face of an expanding
      aneurysm is a valid management option for selected patients.

PMID- 19090627
TI  - Cutting balloon angioplasty in percutaneous carotid interventions.
AB  - PURPOSE: To report a prospective feasibility study of cutting balloon angioplasty
      (CBA) applied in the predilation phase of carotid artery stenting (CAS) in highly
      calcified lesions. METHODS: From January 2003 to February 2007, 178 consecutive
      patients (109 men; mean age 73.1+/-7.3 years) with highly calcified carotid
      lesions underwent CAS with CBA applied as a pre-specified strategy in the
      predilation phase of the procedure. All steps in the procedure were performed
      under cerebral filter protection. The cutting balloon ranged in diameter from 3
      to 4 mm and was inflated at nominal pressures in the target lesion. Pre-CBA
      dilation with a low-profile coronary balloon was performed only when the cutting
      balloon was not able to cross the lesion. Selection of the filters and stents was
      at the operator's discretion. Primary endpoints were the all stroke and death
      rates at 30 days and 6 months. Secondary endpoints included cutting balloon
      success (positioning and full balloon inflation), CAS technical success (residual
      angiographic stenosis <30%), CAS procedural success (technical success and no
      complications), and in-hospital major complications. RESULTS: Cutting balloon
      success was achieved in all 178 patients. In 32 (18.0%), pre-CBA dilation was
      necessary due to inability to cross the lesion with the cutting balloon
      initially. CAS technical success was achieved in all patients. One (0.6%) patient
      suffered transient neurological intolerance due to flow cessation from massive
      debris in the distal filter; this event was completely resolved after the filter
      was removed (CAS procedural success 99.4%). One patient suffered a major stroke
      at day 15 (0.6% 30-day all stroke and death rate). At the 6-month follow-up, 174
      (97.7%) patients were evaluated; 1 patient died from myocardial infarction at day
      35, and 2 patients died from non-neurological or cardiac causes at days 103 and
      158. The cumulative all stroke and death rate was 2.2%. CONCLUSION: These data
      suggest that CBA performed during the predilation phase of CAS in highly
      calcified lesion is a safe and useful method to prepare this lesion subset for
      stenting.

PMID- 19090628
TI  - Effects of stent design and atherosclerotic plaque composition on arterial wall
      biomechanics.
AB  - PURPOSE: To examine the solid mechanical effects of varying stent design and
      atherosclerotic plaque stiffness on the biomechanical environment induced in a
      diseased artery wall model. METHODS: Computational modeling techniques were
      employed to investigate the final radius of the lumen and artery wall stresses
      after stent implantation. Two stent designs were studied (one stiff and one less
      stiff). The stenotic artery was modeled as an axisymmetrical diseased vessel with
      a 20% stenosis by diameter. The material properties of the diseased tissue in the
      artery models varied. Atherosclerotic plaques half as stiff (0.5x), of equal
      stiffness (1.0x), or twice as stiff (2.0x) as the artery wall were investigated.
      RESULTS: Final lumen radius was dependent on stent design, and the stiffer stent
      deformed the artery to an approximately 10% greater radius than the more
      compliant design. Alternatively, circumferential stress levels were dependent on
      both stent design and plaque material properties. Overall, the stiffer stent
      subjected the artery wall to much higher stress values than the more compliant
      design, with differences in peak values of 0.50, 0.31, and 0.09 MPa for the 2.0x,
      1.0x, and 0.5x stiff plaques, respectively. CONCLUSION: Evidence suggests that a
      judicious choice of stent design can minimize stress while maintaining a patent
      lumen in stenotic arteries. If confronted with a rigid, calcified plaque, stent
      design is more important, as design differences can impose dramatically different
      stress fields, while still providing arterial patency. Alternatively, stent
      design is not as much of an issue when treating a soft, lipid-laden plaque, as
      stress fields do not vary significantly among stent designs.

PMID- 19090629
TI  - Limb ischemia after EVAR: an effect of the obstructing introducer?
AB  - PURPOSE: To evaluate the splanchnic and limb metabolic effects of open repair
      (OR) of abdominal aortic aneurysms (AAA) versus endovascular aneurysm repair
      (EVAR) in a pilot study utilizing microdialysis. METHODS: Nine AAA patients (8
      men; mean age 74 years, range 61-85) were treated with EVAR and 9 had an OR (5
      men; mean age 70 years, range 55-85). In the EVAR cases, which were performed
      percutaneously, the external iliac artery was obstructed by the introducer to a
      mean functional stenosis of 70% (52%-100%). Catheters for microdialysis were
      placed subcutaneously above the ankle of the right leg and freely in the
      abdominal cavity to measure the levels of lactate and pyruvate. The
      lactate/pyruvate ratio was calculated as a measure of ischemia. Measurements
      started at the end of surgery and continued for 2 days. Mean values were compared
      using the Mann-Whitney U test. RESULTS: The mean value of intraperitoneal lactate
      during the first day after EVAR was 1.5+/-0.7 mM versus 2.6+/-0.8 mM after OR (p
      = 0.019). The lactate/pyruvate ratio was 10.2+/-2.2 after EVAR and 12.3+/-2.6
      after OR (p = 0.113). Leg lactate mean values were 4.2+/-2.0 mM after EVAR versus
      1.8+/-0.6 mM after OR (p<0.001). The lactate/pyruvate ratio was 20.1+/-8.3 for
      EVAR and 13.7+/-3.3 for OR (p = 0.040). These differences between EVAR and OR
      continued for the second day. CONCLUSION: Intraperitoneally, metabolism was
      slightly increased after OR; however, it was not suggestive of splanchnic
      ischemia. Leg findings reflected a more extensive ischemia after EVAR over 48
      hours, which was a somewhat unexpected finding that may be related to the
      introducer's impact on blood flow to the limb during the intervention. Although
      no clinical consequences were recorded, the finding suggests some benefit of
      minimizing as much as possible the time of reduced perfusion to the limb.

PMID- 19090630
TI  - Ionizing radiation in endovascular interventions.
AB  - Ionizing radiation exposure is an inherent component of endovascular surgery. As
      procedures become more complex, greater radiation exposure is incurred by both
      staff and patient. Radiation doses during endovascular aneurysm repair are
      similar to those recorded during percutaneous coronary interventions. Ionizing
      radiation may cause skin injury, as well as increase the long-term risk of
      malignancy. Endovascular surgeons need to be aware of radiation hazards and take
      all reasonable steps to minimize the risks to both patients and staff.

PMID- 19090631
TI  - Effect of carotid angioplasty and stenting on duplex velocity measurements in a
      porcine model.
AB  - PURPOSE: To evaluate if there are any differences in duplex ultrasound velocity
      measurements between native and stented carotid arteries using duplex ultrasound
      in an animal model. METHODS: The common carotid artery of 5 pigs was exposed
      bilaterally (10 arteries). Diameters and velocities were measured by ultrasound
      in the proximal, mid, and distal native artery at the intended site of stent
      implantation. Measurements were repeated after bilateral stent placement
      (Wallstent versus Precise) under angiographic control. Outcomes of native versus
      stented arteries and Wallstent versus Precise were statistically compared.
      RESULTS: Angiographic measurements matched well with duplex-measured diameters.
      The mean proximal stent diameter (3.5+/-0.5 mm) was significantly smaller than
      the native proximal artery diameter (4.2+/-0.4 mm, p = 0.004), mostly due to
      narrowing of the Wallstent diameter to 3.2+/-0.5 mm (p = 0.009). Proximal, mid,
      and distal segments of the Wallstents were narrower than those of the Precise
      stent, and associated peak systolic velocities (PSV) were higher at the 3
      locations versus the Precise stent, although the differences were not
      statistically significant. Wallstent PSVs were higher than in the native artery
      at the proximal, mid, and distal segments, respectively; again, the differences
      were not statistically significant. CONCLUSION: Stent placement caused anatomical
      and hemodynamic alterations. Narrowings and associated increased velocities were
      noted. Such alterations, however, were stent-type dependent and did not justify a
      general approach to new velocity criteria indiscriminately applied to all stents.

PMID- 19090632
TI  - Bailout percutaneous external shunt to restore carotid flow in a patient with
      acute type A aortic dissection and carotid occlusion.
AB  - PURPOSE: To report the use of an external common femoral to carotid artery shunt
      in the setting of acute type A aortic dissection associated with carotid
      occlusion and stroke. TECHNIQUE: The procedure is illustrated in a 52-year-old
      man who presented with a type A dissection extending into the innominate trunk,
      with associated occlusion of the right common carotid artery (CCA). Angiography
      showed no collateral circulation to the right cerebral hemisphere. To re
      establish brain perfusion in this setting, a percutaneous external shunt was
      installed from the common femoral artery to the right CCA. The 5-F femoral sheath
      used during diagnostic angiography was replaced by an 8-F femoral introducer
      securely fixed to the skin with silk sutures. Ultrasound-guided percutaneous CCA
      access was obtained using an 18-G needle and a 6-F introducer, also sutured to
      the skin. The ICA and intracranial branches showed no evidence of thrombosis at
      this level. A plastic tube was used to connect the femoral and carotid sheath
      side arms to restore ICA flow. Transcranial Doppler showed normal flow at the
      right middle cerebral artery after shunt placement. The patient was immediately
      transferred to the operating room for aortic surgery, during which an
      intrapericardially ruptured aorta was found. The ascending aorta and proximal
      arch were replaced under cardiopulmonary bypass and circulatory arrest, but the
      patient died during the procedure due to uncontrolled bleeding. CONCLUSION: A
      temporary percutaneous external femoral-carotid shunt can restore blood flow to
      the brain whenever the carotid artery is occluded by the dissection flap and
      adequate collateral flow is absent.

PMID- 19090633
TI  - Biomechanical response of stented carotid arteries to swallowing and neck motion.
AB  - PURPOSE: To examine the effects of swallowing and side-to-side head turning on
      stents in the internal carotid artery. METHODS: Seven patients (4 men; mean age
      76.9 years) who underwent carotid artery stenting for the treatment of
      atherosclerotic cervical carotid artery disease were examined with cine
      fluoroscopy. Geometric processing techniques were used to quantify carotid stent
      deformations due to head turning and swallowing forces. The variables measured
      included radial, axial, and crush deformations, as well as radii of stent
      curvatures during tested maneuvers. RESULTS: Radial deformations of the stented
      vessels were significantly less than axial and crush deformations, ranging from 
      10.2% to 15.5%. Axial deformations in response to both swallowing and head
      turning were positive (average 4.5%, range -14.5% to 14.1%), indicating a general
      lengthening of the stented vessel due to biomechanical motions. Crush strains
      exhibited the largest range of all of the deformation modes during both
      swallowing and head turning. Strain values ranged from -18.7% to 25.9% in the
      anteroposterior direction and from -25.6% to 21.9% in the lateral direction. Head
      turning produced fairly symmetrical crushing of the stent. Conversely, swallowing
      resulted in a preferential medial crush of the stented artery due to contraction
      of the pharyngeal constrictor muscles. Curvature measurements revealed a tightest
      radius of curvature of approximately 1.5 cm during ipsilateral head turning, with
      average values during both swallowing and head turning of approximately 10 cm.
      CONCLUSION: In general, head turning toward the stented artery produced greater
      deformation in the vessels than swallowing. Since patients are expected to
      undergo far more swallowing cycles than head turns, however, the accumulated
      deformations from swallowing may be more significant and should be considered in
      the design of fatigue resistant stents for carotid arteries.

PMID- 19090634
TI  - Endoleaks following endovascular repair of thoracic aortic aneurysm: etiology and
      outcomes.
AB  - PURPOSE: To evaluate the incidence and natural history of endoleaks following
      thoracic endovascular aortic repair (TEVAR) of thoracic aortic aneurysm (TAA).
      METHODS: A retrospective review was conducted on 200 TAA patients (122 men; mean
      age 69+/-12 years) who underwent elective TEVAR in the descending thoracic aorta
      between January 2001 and December 2006. The mean aneurysm diameter was 66 mm
      (range 50-124), and most (75%) of the aneurysms were atherosclerotic in origin.
      Medical records and multidetector computed tomography studies were evaluated on a
      3-dimensional workstation to categorize endoleak, establish morphological
      characteristics, and assess outcomes. The outcomes following any secondary
      interventions were noted in the context of endoleak etiology and the magnitude of
      the intervention. RESULTS: Over a mean follow-up of 30 months (range 12-73), 39
      (19.5%) patients developed an endoleak (33 primary and 8 secondary); 3 people had
      2 distinct types of endoleaks. Endoleaks were associated with the presence of a
      carotid-subclavian bypass (p = 0.0001) and lengthy aortic coverage by the stent
      graft (p = 0.005). The proportion of the 170 patients with a Zenith stent-graft
      who had an endoleak (17%, n = 39) was significantly lower (p<0.01) than the
      proportion of endoleaks (34%, n = 10) in the 30 patients with Gore or Talent
      devices. Secondary interventions for endoleak were performed in 79% of type I,
      24% of type II, and 57% of type III endoleaks. CONCLUSION: In this study, 1 in 5
      TAA patients with TEVAR had endoleak. Most type I and III endoleaks required
      secondary intervention, while conservative treatment was most frequent for type
      II. Characterization of endoleak type was not always precise, and routine
      surveillance of all patients with endoleak is recommended.

PMID- 19090635
TI  - Re: "midterm results of a sirolimus-eluting stent implanted for recurrent carotid
      in-stent restenosis".

PMID- 19090636
TI  - Nutrition education and support program for community-dwelling adults with
      intellectual disabilities.
AB  - To test the efficacy, acceptability, and appropriateness of a nutrition education
      and support program, 4 community-based group homes for adults with intellectual
      or developmental disabilities participated in a pilot intervention with extended
      baseline period and pre-post-test design. Adults (N = 32) with intellectual or
      developmental disabilities, 20 direct service staff, 4 managers of group homes,
      and 2 health specialists at private service providers participated in the
      intervention, consisting of a system of nutrition supports in nutrition education
      and guidelines, menu and meal planning, grocery shopping, and cooking designed
      for the special needs of this population. Positive impacts were found using the
      program, including fidelity measures, food systems changes and acceptability to
      users, planned and served foods, and cost changes associated with implementation.

PMID- 19090637
TI  - Embedded, constant time delay instruction by peers without disabilities in
      general education classrooms.
AB  - This study investigated the effects of a training package (written manual,
      individual training session, and ongoing verbal feedback) on middle school peer
      tutors' use of embedded, constant time delay procedures and on the learning
      outcomes for students with significant cognitive disabilities in general
      education settings. The study data showed that peer tutors could be trained
      quickly and efficiently to accurately use constant time delay and embedded
      instructional techniques in general education settings. The data also showed that
      peer tutors delivering embedded, constant time delay instruction in general
      education settings resulted in skill acquisition for students with significant
      cognitive disabilities. In addition, teacher and peer tutor measures were
      positive about the social validity of the procedures and outcomes of the peer
      delivered embedded instructional package.

PMID- 19090638
TI  - "I like others to not try to fix me": agency, independence, and autism.
AB  - This article is based on an interpretevist, qualitative research project
      conducted with individuals labeled with autism who type to communicate.
      Researchers engaged in participant observation and conducted open-ended
      interviews with 9 participants who were working to develop independent typing
      skills. Three findings emerged from this research. First, participants shaped a
      notion of independence that included dependence on various supports. Second,
      researchers recognized the concept of agency in the interactions between
      participants and their communication facilitators. Third, participants exercised
      control of their lives through these expressions of agency.

PMID- 19090639
TI  - Using a speech-generating device to enhance communicative abilities for an adult
      with moderate intellectual disability.
AB  - For adults with disabilities who are unable to speak, the literature recommends
      that intervention include augmentative and alternative communication (AAC) to
      improve communication and interactions with others. Some adults with moderate
      intellectual disabilities who exhibit limited functional speech are often
      overlooked as candidates for AAC interventions because they have some speech
      abilities. The perception is that they are too old to improve their language and
      communication skills. This article presents a case report of a 30-year-old woman
      with a moderate intellectual disability and a severe expressive language disorder
      who uses a speech-generating device as a compensatory strategy to facilitate her
      communicative abilities, independence, and self-determination.

PMID- 19090640
TI  - Response to Bellini's (2007) commentary on Lichten and Simon's (2007) "defining
      mental retardation: a matter of life or death".

PMID- 19090641
TI  - A model intervention to improve primary health care for adults with developmental
      disabilities.

PMID- 19090642
TI  - Leadership in the field of intellectual and developmental disabilities.

PMID- 19090643
TI  - Affordability of family care for an individual with intellectual and
      developmental disabilities.

PMID- 19090644
TI  - The 40th anniversary of deinstitutionalization in the United States: decreasing
      state institutional populations, 1967-2007.

PMID- 19090647
TI  - A new anoplocephalid (Cestoda: Cyclophyllidea) from Gallotia atlantica (Reptilia,
      Lacertidae) in the Canary Islands, Spain.
AB  - A new species of anoplocephalid cestode is described from Gallotia atlantica
      (Reptilia, Lacertidae) on the Canary Islands, Spain. Oochoristica feliui n. sp.
      belongs to the group of Oochoristica spp. having circular suckers and fewer than
      25 testes in a single cluster: O. lygosomae Burt, 1933; O. lygosomatis Skinker,
      1935; O. elongata Dupouy et Kechemir, 1973; O. jonnesi Bursey, McAllister and
      Freed, 1997; O. junkea Johri, 1950; O. macallisteri Bursey and Goldberg, 1996; O.
      novaezelandae Schmidt and Allison, 1985; O. parvogenitalis Dupouy and Kechemir,
      1973; and O. sobolevi (Spasskii, 1948) Spaskii, 1951. Oochoristica feliui n. sp.
      differs from these species in a variety of characters such as the number of
      proglottids, size of the scolex and suckers, presence of a neck, size and shape
      of the ovary (divided into 5-6 lobules), ovoid shape of the vitelline gland, a
      spined cirrus, size of eggs, oncosphere and oncosphere hooks, and the presence of
      2 osmoregulatory canals. Gallotia spp. are endemic to the Canary Islands. This is
      the first report of an adult cestode species in this lizard.

PMID- 19090648
TI  - A novel Taenia solium protein that resembles troponin T proteins.
AB  - Taenia solium Linnaeus, 1758 is responsible for taeniasis and cysticercosis,
      which are 2 serious health problems, particularly in developing countries. The
      attempt to identify a 22.5kD possible protective oncospheral antigen by 2
      dimensional gel-electrophoresis, micro-sequencing, and cDNA library screening
      produced a protein of 42kD that possesses a conserved domain similar to that of
      troponin T. Five variants that showed differences at the 5' end were observed at
      the cDNA level. Hyper-immune rabbit sera developed against recombinant GST fused
      protein identified the protein exclusively on activated oncospheres. The 42kD
      protein was tested in an enzyme-linked immunoassay (ELISA) alone and then
      together with the Tso31 protein for the diagnosis of human cysticercosis. When
      both antigens were combined, the test was found to be 85% sensitive and 65%
      specific. The 42kD is a novel T. solium protein that is present exclusively on
      activated oncospheres of this parasite, with poor diagnostic activity against
      taeniasis or human cysticercosis.

PMID- 19090650
TI  - Chemokinetic effect of interleukin-1 beta on cultured Biomphalaria glabrata
      embryonic cells.
AB  - Previous studies have indicated that a molecule with cytokine activity, possibly
      an interleukin-1-like (IL-1) molecule, plays a role in the killing of larval
      stages of the blood fluke Schistosoma mansoni in the snail host Biomphalaria
      glabrata. The purpose of the present experiment was to test the effects of
      recombinant-human IL-1beta (rhIL-1beta) on embryonic B. glabrata (Bge) cell
      motility to determine whether the cells respond to the cytokine. Response was
      measured using a variation of a chemokinetic assay in which cells in culture were
      separated from variable concentrations of rhIL-1beta by a semi-permeable membrane
      containing pores to allow migration. A double staining technique was developed to
      ascertain cell movement across the membrane. The number of cells moving across
      the membrane significantly increased in a concentration-dependent manner relative
      to the presence of increasing amounts of rhIL-1beta below the membrane. The
      number of cells that moved across the membrane increased until a threshold was
      reached, after which migration decreased. Further, the rhIL-1beta-mediated
      increase in Bge cell migration across the membrane was abrogated by the addition
      of IL-1 receptor antagonist protein. These data indicate that Bge cells respond
      specifically to rhIL-1beta. As such, these data also indicate that Bge cells may
      serve as a useful model for elucidation of the role of cytokines or cytokine-like
      molecules in the snail/schistosome relationship.

PMID- 19090651
TI  - PCR assays for detection of Baylisascaris procyonis eggs and larvae.
AB  - The objective of this study was to develop polymerase chain reaction (PCR) assays
      for detection of Baylisascaris procyonis eggs and larvae in fecal, environmental,
      and tissue samples. We have optimized conventional and real-time PCR assays for
      B. procyonis using the mitochondrial cytochrome oxidase 2 gene as the target for
      amplification. The lower limit of detection of the parasite genomic DNA was 10 pg
      in the conventional PCR and 100 fg in the real-time PCR. In both PCR assays,
      specific amplification of a 146 bp product was achieved with DNA extracted from a
      single in vitro hatched B. procyonis larva and also from canine fecal samples
      spiked with as few as 20 unembryonated B. procyonis eggs per gram of feces. The
      PCR assays were successfully used for detection of B. procyonis eggs and larvae
      in fecal, environmental, and tissue samples. No DNA amplification was seen when
      the genomic DNA of related ascarids (including B. transfuga) and a hookworm was
      used as template in the PCR; however, amplification was seen with the very
      closely related B. columnaris.

PMID- 19090652
TI  - Distinct differences in self-assembly of aromatic linear dicarboxylic acids.
AB  - Self-assembly into two-dimensionally ordered supramolecular structures of three
      aromatic dicarboxylic acids-2,6-naphthalenedicarboxylic acid (NDA), 4,4'
      biphenyldicarboxylic acid (BPDA), and 4,4'-stilbenedicarboxylic acid (SDA)-is
      studied at the liquid-solid interface by scanning tunneling microscopy. All
      compounds possess structural similarities, namely, two interconnected aromatic
      moieties and functionalization through two carboxylic groups in linear
      configuration. For all molecules, ordered monolayers were observed on a graphite
      substrate, and the resulting structures can be described as a dense packing of
      one-dimensionally hydrogen-bonded rows. However, concerning the stability of the
      adsorbate layers, the average domain size, and the degree of order, distinct
      differences were noticed. Supported by density functional theory (DFT)
      calculations, these differences are analyzed and explained as a consequence of
      molecular structure, adsorption geometry, and adsorption energy.

PMID- 19090653
TI  - Driving forces underlying the formation of chiral domains of fluorinated diacids
      on graphite.
AB  - The role of intermolecular interactions, molecule-substrate interactions, and
      molecular chirality in the construction of 2-D surface architectures is the
      subject of much current interest. A racemic mixture of long chain hydrocarbons
      was synthesized with terminal carboxylic acid functionalities at each end and two
      amide linkages in the central region of the molecule on either side of two F
      containing chiral centers. Using scanning tunnelling microscopy (STM), we have
      examined how the functionality of these molecules influences their self-assembly
      on a highly oriented pyrolytic graphite (HOPG) surface. The key factors
      determining the nature of ordered domains have been identified.

PMID- 19090654
TI  - Comparative proteomics study of salt tolerance between a nonsequenced extremely
      halotolerant cyanobacterium and its mildly halotolerant relative using in vivo
      metabolic labeling and in vitro isobaric labeling.
AB  - Euhalothece sp. BAA001 is an extremely halotolerant cyanobacterium, and recent
      proteomic investigations have revealed many shared survival strategies with its
      well-studied and moderately halotolerant relative Synechocystis sp. PCC6803. We
      exploit the shared tryptic peptides between these organisms and directly compare
      the relative protein abundance in cells grown in the exact same salt conditions.
      This comparison is made with added salt (NaCl) concentrations of 0, 3, and 6%
      (w/v), where significant abundance differences are explained in terms of
      prioritization of essential cellular processes in relation to salinity tolerance.
      Implementation of (15)N in vivo metabolic labeling in conjunction with
      conventional search software, Mascot, and quantification software MSQUANT allowed
      243 unique proteins to be quantified. The characteristic "stress" response that
      Euhalothece displays in 0% salt is observed through higher abundance of stress
      associated proteins, including a putative DNA binding stress protein and
      antioxidative enzymes. In contrast, Synechocystis expresses a greater number of
      "stress" proteins in 3% and 6% salt. In addition to in vivo metabolic labeling,
      an experiment using in vitro isobaric labeling (iTRAQ) was also carried out,
      which successfully demonstrated its applicability in cross-species proteomics.

PMID- 19090655
TI  - Bulk and surface assembly of branched amphiphilic polyhedral oligomer
      silsesquioxane compounds.
AB  - This study probes the behavior of two series of organic-functionalized core-shell
      silsesquioxane (POSS-M)p-(x/y) derivatives with various hydrophobic-hydrophilic
      terminal group compositions in the bulk state and within mono- and multilayered
      films at the air-water interface and on solid surface. POSS-M refers to mixed
      silsesquioxane cores, in contrast to the geometrically specific POSS compounds.
      It is composed of polyhedra, incompletely condensed polyhedra, ladder-type
      structures, linear structures, and all the possible combinations thereof and
      attracts great interest because of its facile preparation, low polydispersity,
      high yield, and low cost. The two series of (POSS-M)p-(x/y) molecules are
      different in hydrophobic-hydrophilic balance of their terminal groups, with x and
      y respectively referring to the molar percent of -OCONH-C(18)H(37) tails and -OH
      for p = 1 and the percent of -OCONH-C(18)H(37) tails and -OCO-C(6)H(4)COOH
      terminal groups for p = 2. In the bulk state, the presence of aromatic rings in
      (POSS-M)2-(x/y) series resulted in a lower symmetry crystal structure than the
      (POSS-M)1-(x/y) series. Moreover, the (POSS-M)p-(x/y) molecules that contain a
      sufficient amount of -OCONH-C(18)H(37) tails exhibit double endothermic
      transition, which attributed to the melting of alkyl chains followed by the
      melting of the unit cells of (POSS-M) cores. The surface morphologies for the
      various hydrophobic-hydrophilic combinations at surface pressure p = 0.5 mN/m are
      similar to that observed for the classical amphiphilic star polymers. However, at
      higher surface pressure (p > or = 5 mN/m), the POSS-M compounds with lower
      content of hydrophilic groups form a uniform monolayer.

PMID- 19090656
TI  - Naphthalenedicarboximide- vs perylenedicarboximide-based copolymers. Synthesis
      and semiconducting properties in bottom-gate N-channel organic transistors.
AB  - Two new n-channel polymeric semiconductors for organic thin-film transistors
      (TFTs) based on electron-depleted perylene- (PDI) and naphthalene-dicarboxyimide
      (NDI) polymerized with dithiophene are reported: poly{[N,N'-bis(2-octyldodecyl)
      1,4,5,8-naphthalene dicarboximide-2,6-diyl]-alt-5,5'-(2,2'-bithiophene)},
      P(NDI2OD-T2), and poly{[N,N'-bis(2-octyldodecyl)-3,4,9,10-perylenedicarboximide
      (1,7&1,6)-diyl]-alt-5,5'-(2,2'-bithiophene)}, P(PDI2OD-T2). Polymer
      regioregularity and electronic structure strongly depend on the rylene co
      monomer. The use of NDI enables a regioregular and high-molecular-weight polymer
      with greatly stabilized electron transport in ambient. Unoptimized P(NDI2OD-T2)
      based TFTs exhibit good electron mobilities [mu(e) approximately 0.04 (0.01)
      cm(2)/V.s in vacuum (ambient after 16 weeks) vs mu(e) approximately 0.003 (2 x
      10(-4)) cm(2)/V.s in vacuum (ambient after 1.5 week) for P(PDI2OD-T2)] and on-off
      current modulation [I(on):I(off) > 10(6)].

PMID- 19090657
TI  - In situ growing and patterning of aligned organic nanowire arrays via dip
      coating.
AB  - Aligned organic nanowire arrays are grown in situ and patterned via dip coating.
      By optimizing the stick-slip motion, the solvent evaporation conditions, and the
      solution concentration, parallel organic nanowire arrays with tunable length and
      desirable density and periodicity are directly grown and aligned on the
      substrate. Organic FETs based on the organic nanowire array have been
      successfully fabricated with a mobility of 1 x 10(-4) cm(2) .V(-1).s(-1).

PMID- 19090658
TI  - Strong second harmonic generation from the tantalum thioarsenates A3Ta2AsS11 (A =
      K and Rb).
AB  - The strongly anisotropic thioarsenates A(3)Ta(2)AsS(11) are stabilized in a
      polysulfide flux. All compounds contain the same parallel
      (1)/(infinity)[Ta(2)AsS(11)(3-)] polymeric anionic chains, but the size of the
      alkali-metals has a profound effect on the packing of the chains. The K(+) or
      Rb(+) favor noncentrosymmetric packing of the chains, whereas the larger Cs(+)
      favors the centrosymmetric packing. The chains feature the combination of two
      asymmetric units [Ta(2)S(11)] and [AsS(3)] and exhibit strong nonlinear optical
      (NLO) second harmonic generation (SHG) response. Polycrystalline samples exhibit
      is up to approximately 15 times stronger SHG than that of commercially used
      AgGaSe(2).

PMID- 19090659
TI  - Four-dimensional docking: a fast and accurate account of discrete receptor
      flexibility in ligand docking.
AB  - Many available methods aimed at incorporating the receptor flexibility in ligand
      docking are computationally expensive, require a high level of user intervention,
      and were tested only on benchmarks of limited size and diversity. Here we
      describe the four-dimensional (4D) docking approach that allows seamless
      incorporation of receptor conformational ensembles in a single docking simulation
      and reduces the sampling time while preserving the accuracy of traditional
      ensemble docking. The approach was tested on a benchmark of 99 therapeutically
      relevant proteins and 300 diverse ligands (half of them experimental or marketed
      drugs). The conformational variability of the binding pockets was represented by
      the available crystallographic data, with the total of 1113 receptor structures.
      The 4D docking method reproduced the correct ligand binding geometry in 77.3% of
      the benchmark cases, matching the success rate of the traditional approach but
      employed on average only one-fourth of the time during the ligand sampling phase.

PMID- 19090660
TI  - Beneficial effect of young oocytes for rabbit somatic cell nuclear transfer.
AB  - This study was designed to examine the effect of the age of rabbit oocytes on the
      developmental potential of cloned embryos. The metaphase II oocytes used for
      nuclear transfer (NT) were collected at 10, 12, 14, and 16 h post-hCG injection
      (hpi). The total number of oocytes collected per donor (21.4-23.7) at 12 to 16
      hpi was similar, but significantly higher than that collected at 10 hpi (16.2).
      Additionally, a significant improvement in blastocyst development was achieved
      with embryos generated by electrically mediated cell fusion (56.0%), compared to
      those from nuclear injection (13.1 %) (Experiment 1). Markedly higher blastocyst
      development (45.8-54.5%) was also achieved with oocytes collected at 10-12 hpi
      than from those collected 14-16 hpi (8.3-14.3%) (Experiment 2). In Experiment 3,
      the blastocyst rates of NT embryos derived from oocytes harvested 12 hpi (39.2
      42.8 %) were significantly higher than from those collected at 16 hpi (6.8-8.4 %)
      (p < 0.05), regardless of the donor cell age. Kinase activity assays showed
      variable changes of activity in rabbit oocytes over the period of 10-16 hpi;
      however, there was no correlation with preimplantational development (blastocyst
      rate vs. MPF, R = 0.326; blastocyst rate vs. MAPK, R = -0.131). Embryo transfer
      of NT embryos utilizing 12 hpi oocytes resulted in one full-term but stillborn,
      and one live cloned rabbit; thus, an efficiency of 1.7 % (n = 117) (Experiment
      4). These results demonstrated that NT utilizing relatively young rabbit oocytes,
      harvested at 10-12 h after hCG injection, was beneficial for the development of
      NT embryos.

PMID- 19090661
TI  - Human embryonic stem cells with maintenance under a feeder-free and recombinant
      cytokine-free condition.
AB  - We previously reported that cynomolgus monkey embryonic stem (ES) cells could be
      maintained under a feeder-free condition without using recombinant cytokines if
      sizes and numbers of ES colonies were kept within an appropriate range. Here we
      show that this finding is also true with human ES cells (hESCs). The two lines of
      hESCs, khES-1 and khES-3, were appropriately maintained in the absence of feeder
      layers or exogenous cytokines such as fibroblast growth factors, Noggin,
      transforming growth factor beta, and Activin by closely controlling the size and
      number of hESC colonies. High-level expressions of immature markers including
      SSEA-4, Oct-4, and Nanog were detected in feeder-free and cytokine-free hESCs,
      and they formed teratomas when implanted into severe combined immunedeficiency
      (SCID) mice. No chromosomal abnormalities were observed over 20 passages, ruling
      out the possibility that special clones with growth advantages had been selected.
      Global protein expression profiles were quite similar among the hESCs maintained
      by our feeder- and cytokine-free method, by coculture with mouse embryonic
      fibroblasts (MEFs) and by a feeder-free method using conditioned media of MEFs.
      However, the activation level of Akt, an important player for the maintenance of
      ES cells, was highest and the activation level of extracellular signal-regulated
      kinase, a critical player for differentiation of ES cells, was lowest in the
      hESCs maintained by our cytokine-free method. Our results not only show a
      technical improvement for the maintenance of hESCs but also open a new avenue for
      the understanding of autocrine signaling networks of hESCs.

PMID- 19090662
TI  - Relationship between oxygen defects and the photocatalytic property of ZnO
      nanocrystals in Nafion membranes.
AB  - ZnO nanocrystals with different oxygen defects (type and concentration) are
      successfully prepared via the templating method in Nafion membranes.
      Photoluminescence and infrared characterizations reveal that the concentration of
      oxygen defects (oxygen vacancy and interstitial oxygen) is quite different for
      the samples prepared via different synthesis processes. Photocatalytic activity
      measurements show that the sample with a higher amount of oxygen defects exhibits
      excellent activity toward the degradation of rhodamine B. Compared with bulk ZnO,
      ZnO nanocrystals embedded in Nafion membranes have an antiphotocorrosion
      property. The possible photocatalytic mechanism is discussed in detail, and the
      oxygen defects are proposed to be the active sites of the ZnO photocatalyst.

PMID- 19090664
TI  - Biodefense research: a win-win challenge.

PMID- 19090663
TI  - Comparative positron-emission tomography (PET) imaging and phototherapeutic
      potential of 124I- labeled methyl- 3-(1'-iodobenzyloxyethyl)pyropheophorbide-a vs
      the corresponding glucose and galactose conjugates.
AB  - In our present study, 3-(1(')-m-iodobenzyloxyethyl)pyropheophorbide-a methyl
      ester 1, 3-(1'-m-iodobenzyloxyethyl)-17(2)-{(2-deoxy)glucose}pyropheophorbide-a
      2, and 3-(1'-m-iodobenzyloxyethyl)-17(2)-{(1-deoxy)galactose}pyropheophorbide-a 3
      were synthesized and converted into the corresponding (124)I-labeled analogues by
      reacting the intermediate trimethyltin analogues with Na(124)I. Photosensitizers
      1-3 were evaluated for the PDT efficacy in C3H mice bearing RIF tumors at
      variable doses and showed a significant long-term tumor cure. Among the compounds
      investigated, the non-carbohydrate analogue 1 was most effective. These results
      were in contrast to the in vitro data, where compared to the parent analogue the
      corresponding galactose and glucose derivatives showed enhanced cell kill. Among
      the corresponding (124)I-labeled analogues, excellent tumor images were obtained
      from compound 1 in both tumor models (RIF and Colon-26) and the best tumor
      contrast was observed at 72 h after injection. Conjugating a glucose moiety to
      photosensitizer 1 initially diminished its tumor uptake, whereas with time the
      corresponding galactose analogue showed improved tumor contrast.

PMID- 19090665
TI  - [Ru(dpp)(3)][(4-Clph)(4)B](2) nanoislands directly assembled on an ITO electrode
      surface and its electrogenerated chemiluminescence.
AB  - In this work, solid-state tris(4,7-diphenyl-1,10-phenanthroline) ruthenium(II)
      ditetrakis(4-chlorophenyl)borate ([Ru(dpp)(3)][(4-Clph)(4)B](2)) nanoislands are
      assembled spontaneously and simultaneously on an indium-doped tin oxide (ITO)
      glass electrode surface via a facile dewetting procedure. The fabrication process
      is very simple and also amenable to mass production. The as-prepared ruthenium
      complex nanoislands exhibit useful properties. The electrode is more
      electrochemically active and can produce strong, stable, reproducible solid-state
      electrochemiluminescence (ECL) signals using oxalate as the coreactant. The self
      assembled nanoislands exhibit semiconductor-like broad, red-shift ECL spectrum.
      More importantly, they extend the application of the ruthenium complex ECL system
      from the usual alkaline to acidic conditions. The pH turn-off behavior of the ECL
      is observed for the first time and can serve as an ultrasensitive pH sensor
      around physiological pH 7.0. The solid-state [Ru(dpp)(3)][(4-Clph)(4)B](2) ECL
      signal is efficiently inhibited by phenol even at a very low concentration (i.e.,
      20 nM), thus providing the potential for the determination of phenolic compounds
      in practical applications.

PMID- 19090666
TI  - Enhanced optical responses of Au@Pd core/shell nanobars.
AB  - A Pd nanoshell was epitaxially grown on a Au nanorod (NR) via simple seed
      mediated growth. Compared with the cylindrical shape of the Au NR, the Au core/Pd
      shell (Au@Pd) nanorods change to a rectangular shape due to the disappearance of
      {110} facets. The Au NRs exhibit a strong longitudinal surface plasmon resonance
      (LSPR). As Pd is deposited, damping and broadening occur to the LSPR band.
      Interestingly, the LSPR band maximum first shows a small red-shift (ca. 40 nm)
      which then is followed by a blue-shift as the amount of Pd is increased. A
      thickness-dependent LSPR feature of the Pd shell is believed to contribute to the
      shift. At a thinner Pd thickness, the Au@Pd nanobars exhibit a well-defined LSPR
      band in the visible and near-infrared region, which demonstrates a higher
      dielectric sensitivity than that of the corresponding Au NRs. It thus opens up
      the potential of Pd nanostructures for SPR-based sensing. Investigations on the
      surface-enhanced Raman scattering (SERS) indicate that the SERS activities of the
      Au@Pd nanobars at thicknesses smaller than 2.5 nm mainly originate from the Au
      cores; thus, the SERS activities can be improved by tuning the aspect ratio of
      the Au core and/or the Pd shell thickness.

PMID- 19090667
TI  - Proton gradients produced by glucose oxidase microcapsules containing motor F0F1
      ATPase for continuous ATP biosynthesis.
AB  - Glucose oxidase (GOD) microcapsules held together by cross-linker, glutaraldehyde
      (GA), are fabricated by the layer-by-layer (LbL) assembly technique. The lipid
      bilayer containing CF(0)F(1)-ATPase was coated on the outer shell of GOD
      microcapsules. Driven under the proton gradients produced by catalysis of GOD
      microcapsules for glucose, ATP is synthesized from ADP and inorganic phosphate
      catalyzed by the ATPase rotary catalysis. The results show here that ATPase
      reconstituted on the GOD microcapsules retains its catalytic activity.

PMID- 19090668
TI  - Discovery of human macrophage migration inhibitory factor (MIF)-CD74 antagonists
      via virtual screening.
AB  - Macrophage migration inhibitory factor (MIF) is a cytokine that is involved in
      the regulation of inflammation as well as cell proliferation and differentiation.
      Deactivation of MIF by antibodies or inhibition of MIF binding to its receptor,
      CD74, attenuates tumor growth and angiogenesis. To discover small-molecule
      inhibitors of MIF's biological activity, virtual screening was performed by
      docking 2.1 million compounds into the MIF tautomerase active site. After visual
      inspection of 1200 top-ranked MIF-ligand complexes, 26 possible inhibitors were
      selected and purchased and 23 of them were assayed. The in vitro binding assay
      for MIF with CD74 revealed that 11 of the compounds have inhibitory activity in
      the micromolar regime, including four compounds with IC(50) values below 5
      microM. Inhibition of MIF tautomerase activity was also established for many of
      the compounds with IC(50) values as low as 0.5 microM; Michaelis-Menten analysis
      was performed for two cases and confirmed the competitive inhibition.

PMID- 19090669
TI  - A novel isotherm, modeling self-assembled monolayer adsorption and structural
      changes.
AB  - Self-assembled monolayers (SAMs) have numerous applications, for example, engine
      wear inhibitors, surface profiling signal enhancement, nanostructure production,
      sensor production, and catalysis. The adsorbed SAM structure has a major impact
      on the properties of the outer monolayer surface which dictates the performance
      and viability of the SAM for individual applications. Substrate growth phases of
      SAMs have been extensively studied, and two structures have been identified.
      Initially, a lying down SAM structure is formed that evolves into a standing up
      structure. It is often critical to know how both structures form as a function of
      substrate immersion time to be able to design the properties of this structure.
      The formation of mercaptopropionic acid (MPA) SAMs on gold has been studied.
      Electrochemical impedance spectroscopy (EIS) was used to measure the adsorption
      isotherms at five temperatures in the range 4-40 degrees C. Infrared reflectance
      absorption spectroscopy (IRRAS) was also used, and the results show close
      agreement. A new monolayer adsorption isotherm is proposed which models SAM
      structure formation as a function of immersion time, representing all phases of
      SAM adsorption. This model represents a significant improvement on previous
      models based on Langmuir and Kisliuk adsorption isotherms that only model the
      fractional coverage of a surface with a SAM. The new model predicts the optimum
      immersion time taken for an MPA monolayer on gold to attain a surface saturated
      with MPA. It accounts for temperature effects on the rate of formation and the
      degree of monolayer disorder. It has potential for use in other SAM systems and
      may become the method of choice for modeling many instances of sequential
      substrate adsorption of two different structures, each of which exhibits
      different properties, as a function of immersion time.

PMID- 19090670
TI  - Hofmeister effect on the interfacial free energy of aliphatic and aromatic
      surfaces studied by chemical force microscopy.
AB  - This work describes chemical force microscopy (CFM) studies of specific-ion
      effects on the aqueous interfacial free energy of hydrophobic monolayers. CFM
      measurements allow for the characterization of interfacial properties on length
      scales below 100 nm. The ions chosen span the range of the Hofmeister series,
      from the kosmotropic Na(2)SO(4) to the chaotropic NaSCN. The salt concentrations
      used are typical of many laboratory processes such as protein crystallization, 2
      3 M. Both aliphatic (terminal methyl) and aromatic (terminal phenyl) monolayers
      were examined, and rather pronounced differences were observed between the two
      cases. The specific-ion dependence of the aliphatic monolayer closely follows the
      Hofmeister series, namely the chaotropic ions lowered the interfacial free energy
      and the kosmotropic ions increased the interfacial free energy. However, the
      aromatic monolayer had significant deviations from the Hofmeister series.
      Possible origins for this difference are discussed.

PMID- 19090671
TI  - New carbazole-based fluorophores: synthesis, characterization, and aggregation
      induced emission enhancement.
AB  - A series of new carbazole-based luminophores (1-12) were synthesized and well
      characterized, which demonstrated aggregation-induced emission enhancement (AIEE)
      properties. The obtained experimental results demonstrated that the attachment of
      aromatic rotors to luminophore moieties would lead to the decreased quantum
      yields (measured in diluted solutions); the more rotors attached, the smaller the
      quantum yields tested. This further confirmed that the AIEE phenomena were caused
      by the restriction of the intramolecular vibrational and rotational motions in an
      indirect manner.

PMID- 19090672
TI  - Rhodopsin activity varies in proteoliposomes prepared by different techniques.
AB  - A variety of techniques are currently in use for preparing protein-containing
      lipid vesicles known as proteoliposomes. However, the functionality of membrane
      protein in proteoliposomes prepared by various techniques has rarely been
      evaluated directly. We prepared rhodopsin-containing proteoliposomes consisting
      of asolectin or native retinal rod outer segment disk lipids using n-octyl beta-d
      glucopyranoside and the detergent dialysis (DD) and rapid dilution (RD)
      techniques and measured the activity of rhodopsin using equilibrium UV/vis and
      flash photolysis spectroscopy. A significant difference in rhodopsin activity was
      observed in proteoliposomes prepared by these techniques. The equilibrium
      constant of metarhodopsin I-metarhodopsin II is 30-45% higher, and the apparent
      rate constant of MII formation is up to 3-fold faster in proteoliposomes prepared
      by RD vs DD. The DD technique produced larger yet more heterogeneous vesicles,
      while the RD technique yielded smaller and more homogeneous vesicles, as
      determined by electron microscopy and isopicnic centrifugation. Both
      proteoliposomes and empty lipid vesicles lacking rhodopsin were formed in the DD
      preparation, while only proteoliposomes were formed in the RD preparation. Under
      identical conditions, proteoliposomes prepared by RD have a higher L/P ratio,
      which is consistent with the higher level of rhodopsin activity in RD
      proteoliposomes. Overall, the results presented here suggest that the RD
      technique has an advantage over the DD technique in terms of preserving optimal
      rhodopsin activity and controlling the lipid to protein ratio in the final
      proteoliposomes.

PMID- 19090673
TI  - Involvement of Bcl-2 family in apoptosis and signal pathways induced by cigarette
      smoke extract in the human airway smooth muscle cells.
AB  - Chronic obstructive pulmonary disease (COPD) is a highly prevalent airway disease
      characterized by an abnormal inflammatory response of the lungs to noxious
      particles and gases. Cigarette smoking remains a major risk factor for COPD
      development; however, little is known about its effect on human airway smooth
      muscle cells (HASMCs). The aim of this study is to examine whether apoptosis is
      involved in cigarette smoke extract (CSE)-induced HASMC death and the molecular
      mechanisms underlying it. Our studies have shown that CSE increased the level of
      reactive oxygen species (ROS) and cell apoptosis of HASMCs in a dose- and time
      dependent manner, and the ROS scavenger N-acetyl-cysteine abrogated the effect of
      ROS level and apoptosis on HASMCs. Further, the expression of Bax, Bad, and Fas
      was increased but Bcl-2 and nuclear factor-kappaB (NF-kappaB) was decreased in a
      dose- and time-dependent fashion in CSE-induced apoptosis in HASMCs. Taken
      together, CSE could inhibit the cell growth and induce apoptosis of HASMCs
      through both the mitochondrial pathway and death receptor pathway. Oxidative
      stress and inhibition of NF-kappaB expression caused by CSE may play important
      roles in apoptosis and inhibition of cell growth in HASMCs.

PMID- 19090674
TI  - Implications of HIV-1 M group polymorphisms on integrase inhibitor efficacy and
      resistance: genetic and structural in silico analyses.
AB  - The extensive polymorphisms among HIV-1 subtypes have been implicated in drug
      resistance development. Integrase inhibitors represent the latest addition to the
      treatment of HIV-1, and their efficacy and resistance patterns among M group
      strains are currently under investigation. This study analyzed the intersubtype
      variation within 108 integrase sequences from seven subtypes. The residues
      associated with catalytic activity and primary resistance to raltegravir were
      highly conserved among all strains. Variations were observed in residues
      associated with secondary resistance. Molecular modeling studies indicated a two
      way binding mode of raltegravir that explains the resistance pathways and the
      implication of nonconservative mutations in integrase-raltegravir interactions.

PMID- 19090675
TI  - ERdj3, a luminal ER DnaJ homologue, binds directly to unfolded proteins in the
      mammalian ER: identification of critical residues.
AB  - ERdj3 was identified as a soluble, lumenal DnaJ family member that binds to
      unassembled immunoglobulin heavy chains along with the BiP chaperone complex in
      the endoplasmic reticulum of mammalian cells. Here we demonstrated that ERdj3
      binds directly to unfolded substrates. Secondary structure predictions suggested
      that the substrate binding domain of ERdj3 was likely to closely resemble Ydj1, a
      yeast cytosolic DnaJ family member, which was previously crystallized with a
      peptide bound to the C-terminal fragment composed of domains I, II, and III.
      Mutation of conserved residues in domain I, which formed the peptide binding site
      in Ydj1, affected ERdj3's substrate binding ability in mammalian cells and in
      vitro binding studies. Somewhat unexpectedly, we found that domain II, which is
      highly conserved among ERdj3 homologues, but very different from domain II of
      Ydj1, was also critical for substrate binding. In addition, we demonstrated that
      ERdj3 forms multimers in cells and found that the conserved carboxy-terminal
      residue phenylalanine 326 played a critical role in self-assembly. In vitro
      binding assays revealed that mutation of this residue to alanine diminished
      ERdj3's substrate binding ability, arguing that multimerization is important for
      substrate binding. Together, these studies demonstrate that the Ydj1 structure is
      conserved in another family member and reveal that among this group of DnaJ
      proteins domain II, which is not present in the closely related type II family
      members, also plays an essential role in substrate binding.

PMID- 19090676
TI  - Spectroscopic definition of the biferrous and biferric sites in de novo designed
      four-helix bundle DFsc peptides: implications for O2 reactivity of binuclear non
      heme iron enzymes.
AB  - DFsc is a single chain de novo designed four-helix bundle peptide that mimics the
      core protein fold and primary ligand set of various binuclear non-heme iron
      enzymes. DFsc and the E11D, Y51L, and Y18F single amino acid variants have been
      studied using a combination of near-IR circular dichroism (CD), magnetic circular
      dichroism (MCD), variable temperature variable field MCD (VTVH MCD), and X-ray
      absorption (XAS) spectroscopies. The biferrous sites are all weakly
      antiferromagnetically coupled with mu-1,3 carboxylate bridges and one 4
      coordinate and one 5-coordinate Fe, very similar to the active site of class I
      ribonucleotide reductase (R2) providing open coordination positions on both irons
      for dioxygen to bridge. From perturbations of the MCD and VTVH MCD the iron
      proximal to Y51 can be assigned as the 4-coordinate center, and XAS results show
      that Y51 is not bound to this iron in the reduced state. The two open
      coordination positions on one iron in the biferrous state would become occupied
      by dioxygen and Y51 along the O(2) reaction coordinate. Subsequent binding of Y51
      functions as an internal spectral probe of the O(2) reaction and as a proton
      source that would promote loss of H(2)O(2). Coordination by a ligand that
      functions as a proton source could be a structural mechanism used by natural
      binuclear iron enzymes to drive their reactions past peroxo biferric level
      intermediates.

PMID- 19090677
TI  - Structural and kinetic analyses of macrophage migration inhibitory factor active
      site interactions.
AB  - Macrophage migration inhibitory factor (MIF) is a secreted protein expressed in
      numerous cell types that counters the antiinflammatory effects of glucocorticoids
      and has been implicated in sepsis, cancer, and certain autoimmune diseases.
      Interestingly, the structure of MIF contains a catalytic site resembling the
      tautomerase/isomerase sites of microbial enzymes. While bona fide physiological
      substrates remain unknown, model substrates have been identified. Selected
      compounds that bind in the tautomerase active site also inhibit biological
      functions of MIF. It had previously been shown that the acetaminophen metabolite,
      N-acetyl-p-benzoquinone imine (NAPQI), covalently binds to the active site of
      MIF. In this study, kinetic data indicate that NAPQI inhibits MIF both covalently
      and noncovalently. The structure of MIF cocrystallized with NAPQI reveals that
      the NAPQI has undergone a chemical alteration forming an acetaminophen dimer (bi
      APAP) and binds noncovalently to MIF at the mouth of the active site. We also
      find that the commonly used protease inhibitor, phenylmethylsulfonyl fluoride
      (PMSF), forms a covalent complex with MIF and inhibits the tautomerase activity.
      Crystallographic analysis reveals the formation of a stable, novel covalent bond
      for PMSF between the catalytic nitrogen of the N-terminal proline and the sulfur
      of PMSF with complete, well-defined electron density in all three active sites of
      the MIF homotrimer. Conclusions are drawn from the structures of these two MIF
      inhibitor complexes regarding the design of novel compounds that may provide more
      potent reversible and irreversible inhibition of MIF.

PMID- 19090678
TI  - Effects of basis set superposition error on optimized geometries and complexation
      energies of organo-alkali metal cation complexes.
AB  - Theoretical studies were performed to study the binding of alkali metal cations,
      X(+) (X = Li, Na, K), to poly(ethylene oxide) (PEO, I), poly(ethylene amine)
      (PEA, II), and poly(ethylene N-methylamine) (PEMA, III) by the Hartree-Fock (HF)
      and B3LYP methods using the 6-31G(d) and 6-311+G(d,p) basis sets. Two types of
      complex were considered in this study: a singly coordinated system (SCS) and a
      doubly coordinated system (DCS). Complexation energies were calculated both
      without and with basis set superposition error (BSSE). Because of the strong
      charge-dipole interactions, the complexation energies were largely negative and
      decreased in the order Li(+) > Na(+) > K(+). Three possible counterpoise (CP)
      approaches were examined in detail. In the case of the function CP (fCP)
      correction, the complexation energies exhibited an unusual trend because of the
      deformation of the subunits. This problem was solved by including geometry
      relaxation in the CP-corrected (GCP) interaction energies. The effects on the
      structures and vibrational frequencies were small when the complexes were
      reoptimized on the CP-corrected potential energy surface (PES).

PMID- 19090679
TI  - Rate constant rules for the automated generation of gas-phase reaction
      mechanisms.
AB  - The capability of kinetic models to predict complex chemical systems has
      enormously improved in the last decades, making them an increasingly important
      tool for process development and optimization. Extension of these approaches to
      even more complex systems is hindered not only by the geometrically increasing
      number of reactions and species to be considered but also by the necessity of
      assigning accurate rate constants to all of the reactions. The recent
      developments in automated mechanism generators can address the tedious
      bookkeeping issues. The requirement for development of accurate rate constant
      estimates remains the job of the kineticist. This task has been aided
      immeasurably by the combined advances in electronic structure methods and
      computer performance. This article describes two areas of rate estimation. First,
      we discuss the development of H abstraction rate estimates from C-H bonds in
      alkanes, cycloalkanes, and allylic systems by H atoms and point to a surprising
      result found for cyclopentane. Second, we briefly review our investigation of the
      ethyl + O(2) reaction and demonstrate the suitability of the QRRK/MSC approach
      for automated mechanism generation. We conclude with some suggestions for future
      work in this area.

PMID- 19090681
TI  - Conformational relaxation paths in tryptamine.
AB  - The relative fluorescence intensities of three conformers of tryptamine have been
      determined as a function of stagnation pressure and nozzle temperature in a
      supersonic expansion. The relative intensities of the conformers that are
      connected by different direct and indirect interconversion paths on the potential
      energy hypersurface differ considerably depending on the experimental conditions.
      The energies of the local minima and some transition states interconnecting them
      are studied on the ab initio level of theory. From the energies of the barriers
      and vibrational frequencies at the stationary points, conformer interconversion
      rates k(T) and k(E) have been obtained using statistical theories. In the cases
      experimentally observed here, vibrational cooling rates and interconversion rates
      must be of the same order of magnitude, while RRKM theory considerably
      overestimates k(E) values, most probably due to an insufficient consideration of
      anharmonic coupling of the vibrational modes in tryptamine.

PMID- 19090682
TI  - Pillared porphyrin homologous series: intergrowth in metal-organic frameworks.
AB  - We report three new porphyrin-based, pillared paddle-wheel homologous series:
      porphyrin paddle-wheel frameworks PPF-3, -4, and -5. These compounds are
      assembled from free base or palladium tetrakis(4-carboxyphenyl)porphine,
      M(NO(3))(2) (M = Co and Zn), and 4,4'-bipyridine via solvothermal reactions. The
      resulting solids exhibit 3D metal-organic frameworks, where 2D layers are
      pillared by bipyridine with three different packing arrangements.

PMID- 19090683
TI  - Small-angle neutron scattering and volumetric studies of dilute solutions of N,N'
      dimethylpropyleneurea in heavy water.
AB  - Small-angle neutron scattering experiments and density measurements were
      performed on dilute solutions of N,N'-dimethylpropyleneurea (DMPU) in heavy water
      in the mole fraction range 0.005(0.0025)-0.05 at 288.15, 298.15 and 313.15 K.
      From the experimental results values of the radius of gyration, second osmotic as
      well as second and third molal volume virial coefficients, and Kirkwood-Buff
      integrals were calculated. The results led to the conclusions that DMPU has a
      structure-making effect on water and the pairwise solute-solute interactions
      exhibit no temperature dependence and are less attractive in DMPU solutions than
      in N,N'-dimethylethyleneurea and tetramethylurea solutions.

PMID- 19090684
TI  - Photodynamics in complex environments: ab initio multiple spawning quantum
      mechanical/molecular mechanical dynamics.
AB  - Our picture of reactions on electronically excited states has evolved
      considerably in recent years, due to advances in our understanding of points of
      degeneracy between different electronic states, termed "conical intersections"
      (CIs). CIs serve as funnels for population transfer between different electronic
      states, and play a central role in ultrafast photochemistry. Because most
      practical photochemistry occurs in solution and protein environments, it is
      important to understand the role complex environments play in directing excited
      state dynamics generally, as well as specific environmental effects on CI
      geometries and energies. In order to model such effects, we employ the full
      multiple spawning (FMS) method for multistate quantum dynamics, together with
      hybrid quantum mechanical/molecular mechanical (QM/MM) potential energy surfaces
      using both semiempirical and ab initio QM methods. In this article, we present an
      overview of these methods, and a comparison of the excited-state dynamics of
      several biological chromophores in solvent and protein environments. Aqueous
      solvation increases the rate of quenching to the ground state for both the
      photoactive yellow protein (PYP) and green fluorescent protein (GFP)
      chromophores, apparently by energetic stabilization of their respective CIs. In
      contrast, solvation in methanol retards the quenching process of the retinal
      protonated Schiff base (RPSB), the rhodopsin chromophore. Protein environments
      serve to direct the excited-state dynamics, leading to higher quantum yields and
      enhanced reaction selectivity.

PMID- 19090685
TI  - Imaging molecular orbitals by scanning tunneling microscopy on a passivated
      semiconductor.
AB  - Decoupling the electronic properties of a molecule from a substrate is of crucial
      importance for the development of single-molecule electronics. This is achieved
      here by adsorbing pentacene molecules at low temperature on a hydrogenated
      Si(100) surface (12 K). The low temperature (5 K) scanning tunneling microscope
      (STM) topography of the single pentacene molecule at the energy of the highest
      occupied molecular orbital (HOMO) tunnel resonance clearly resembles the native
      HOMO of the free molecule. The negligible electronic coupling between the
      molecule and the substrate is confirmed by theoretical STM topography and
      diffusion barrier energy calculations.

PMID- 19090687
TI  - Enhanced cyclic performance and lithium storage capacity of SnO2/graphene
      nanoporous electrodes with three-dimensionally delaminated flexible structure.
AB  - To fabricate nanoporous electrode materials with delaminated structure, the
      graphene nanosheets (GNS) in the ethylene glycol solution were reassembled in the
      presence of rutile SnO(2) nanoparticles. According to the TEM analysis, the
      graphene nanosheets are homogeneously distributed between the loosely packed
      SnO(2) nanoparticles in such a way that the nanoporous structure with a large
      amount of void spaces could be prepared. The obtained SnO(2)/GNS exhibits a
      reversible capacity of 810 mAh/g; furthermore, its cycling performance is
      drastically enhanced in comparison with that of the bare SnO(2) nanoparticle.
      After 30 cycles, the charge capacity of SnO(2)/GNS still remained 570 mAh/g, that
      is, about 70% retention of the reversible capacity, while the specific capacity
      of the bare SnO(2) nanoparticle on the first charge was 550 mAh/g, dropping
      rapidly to 60 mAh/g only after 15 cycles. The dimensional confinement of tin
      oxide nanoparticles by the surrounding GNS limits the volume expansion upon
      lithium insertion, and the developed pores between SnO(2) and GNS could be used
      as buffered spaces during charge/discharge, resulting in the superior cyclic
      performances.

PMID- 19090686
TI  - Pyridine-N-oxide analogues of DOTA and their gadolinium(III) complexes endowed
      with a fast water exchange on the square-antiprismatic isomer.
AB  - Two macrocyclic ligands derived from H4dota containing three acetate pendant arms
      and one 2-methylpyridine-N-oxide coordinating unit were synthesized. The ligand
      H3do3apy(NO) (H3L1, 10-[(1-oxidopyridin-2-yl)methyl]-1,4,7,10
      tetraazacyclododecane-1,4,7-triacetic acid) contains an unsubstituted pyridine-N
      oxide ring; the ligand H4do3apy(NO-C) (H4L2, 10-[(4-carboxy-1-oxidopyridin-2
      yl)methyl]-1,4,7,10-tetraazacyclododecane-1,4,7-triacetic acid) is functionalized
      with a carboxylic group in the 4 position of the pyridine ring to allow
      attachment to other molecules. The ligands form octadentate (N4O4 environment)
      Ln(III) complexes, with one water molecule completing the coordination sphere in
      a capping position. The complexes are present in solution exclusively as square
      antiprismatic isomers over the whole lanthanide series. The introduction of the
      carboxylic group to the pyridine-N-oxide unit in H4L2 has no significant effect
      on the hydration number (q = 1) and the water exchange rate of the [Gd(H2O)(L2)]-
      complex compared to the parent [Gd(H2O)(L1)] complex (water residence times: tauM
      = 39 ns for [Gd(H2O)(L1)] and tauM = 34 ns for [Gd(H2O)(L2)]- at 298 K).

PMID- 19090688
TI  - On the use of plasmonic nanoparticle pairs as a plasmon ruler: the dependence of
      the near-field dipole plasmon coupling on nanoparticle size and shape.
AB  - The localized surface plasmon resonance (LSPR) spectral band of a gold or silver
      nanoparticle is observed to shift as a result of the near-field plasmonic field
      of another nanoparticle. The dependence of the observed shift on the
      interparticle distance is used as a ruler in biological systems and gave rise to
      a plasmonic ruler equation in which the fractional shift in the dipole resonance
      is found to decrease near exponentially with the interparticle separation in
      units of the particle size. The exponential decay length constant was observed to
      be consistent among a small range of nanoparticle sizes, shapes, and types of
      metal. The equation was derived from the observed results on disks and spherical
      nanoparticles and confirmed using results on a DNA conjugated nanosphere system.
      The aim of the present paper is to use electron beam lithography and DDA
      calculations to examine the constancy of the exponential decay length value in
      the plasmonic ruler equation on particle size and shape of a number of particles
      including nanoparticles of different symmetry and orientations. The results
      suggest that the exponent is almost independent of the size of the nanoparticle
      but very sensitive to the shape. A discussion of the nanoparticles most suitable
      for different applications in biological systems and a comparison of the
      plasmonic ruler with Forster resonance energy transfer (FRET) is mentioned.

PMID- 19090689
TI  - Expression of human peroxisome proliferator-activated receptors ligand binding
      domain-maltose binding protein fusion protein in Escherichia coli: a convenient
      and reliable method for preparing receptor for screening ligands.
AB  - Human peroxisome proliferator-activated receptors (hPPARs) are ligand-activated
      transcription factors and are the target for the treatment of many diseases.
      Screening of their ligands is mainly based on assays of ligand binding to the
      ligand binding domain (LBD) of hPPARs.However, such assays are difficult because
      of the preparation of hPPARs LBD. In order to yield functional hPPARs LBD for
      screening ligands, hPPARs LBD was fused with maltose-binding protein(MBP) using
      the pMAL-p2x expression system through the gene engineering technique. The
      radioligand binding assay showed that MBP did not affect ligand binding with
      hPPARs LBD in the fusion proteins, which means that MBP-hPPARs LBD can be used
      instead of hPPARs LBD in ligand screening work. The results show that the new
      strategy using MBP as a fusion tag for preparing hPPARs LBD for screening ligands
      is a convenient and reliable method. It may be used to easily obtain the other
      nuclear receptors.

PMID- 19090690
TI  - Development of an aequorin luminescence calcium assay for high-throughput
      screening using a plate reader, the LumiLux.
AB  - A luminescence assay using a new plate reader, the LumiLux (PerkinElmer, Waltham,
      MA), has been validated for high-throughput screening (HTS). In this study, we
      compared the aequorin luminescence-based calcium mobilization assay to the
      fluorescence-based calcium assay. A cell line stably co-expressing apo-aequorin,
      a chimeric G-protein, and a G-protein-coupled dopamine receptor was used to
      screen a collection of 8,106 compounds using the Hamamatsu Photonics
      (Bridgewater, NJ) FDSS6000 and LumiLux as the plate readers. The assay parameters
      evaluated included hit rate correlation, signal-to-noise ratio, and overall assay
      performance calculated by Z and standard deviation. The average Z values and hit
      rates were comparable between assay platforms;however, the standard deviation for
      the agonist aequorin assay was significantly smaller. There was also a
      significant decrease in the number of false-positives with the aequorin assay.
      These results suggest that the aequorin assay in combination with the new plate
      reader, LumiLux, provides a simple, cost-effective, robust, and sensitive assay
      for HTS

PMID- 19090691
TI  - An ion channel library for drug discovery and safety screening on automated
      platforms.
AB  - Ion channels represent the third largest class of targets in drug discovery after
      G-protein coupled receptors and kinases. In spite of this ranking, ion channels
      continue to be under exploited as drug targets compared with the other two groups
      for several reasons. First, with 400 ion channel genes and an even greater number
      of functional channels due to mixing and matching of individual subunits, a
      systematic collection of ion channel-expressing cell lines for drug discovery and
      safety screening has not been available. Second, the lack of high-throughput
      functional assays for ion channels has limited their use as drug targets. Now
      that automated electrophysiology has come of age and provided the technology to
      assay ion channels at medium to high throughput, we have addressed the need for a
      library of ion channel cell lines by constructing the Ion Channel Panel (ChanTest
      Corp., Cleveland, OH). From 400 ion channel genes, a collection of 82 of the most
      relevant human ion channels for drug discovery, safety, and human disease has
      been assembled.Each channel has been stably overexpressed in human embryonic
      kidney 293 or Chinese hamster ovary cells. Cell lines have been selected and
      validated on automated electrophysiology systems to facilitate cost-effective
      screening for safe and selective compounds at earlier stages in the drug
      development process. The screening and validation processes as well as the
      relative advantages of different screening platforms are discussed.

PMID- 19090692
TI  - A high-throughput functional assay for characterization of gamma-aminobutyric
      acid(A) channel modulators using cryopreserved transiently transfected cells.
AB  - The ionotropic -aminobutyric acid (GABA)A receptors are an important family of
      drug targets for a variety of neurological and psychiatric disorders. Selective
      modulation of certain subtypes of the receptor could lead to novel or improved
      therapies. However, the discovery of subtype-selective compounds has been
      hampered by the lack of a high-throughput functional assay and the difficulty in
      establishing stable cell lines expressing GABAA receptor in a proper subunit
      composition. To meet drug discovery need we developed a fluorescent imaging plate
      reader(FLIPR)-based membrane potential assay with sufficient robustness and
      reproducibility for use in a high-throughput format. Two major subtypes of GABAA
      receptor were used: GABAA1 and GABAA2, which are composed of
      (alpha1)2(beta2)2gama2 and (alpha1)2(beta3)2gama2, respectively. We expressed the
      receptors by transiently co-transfecting cells with the three subunit DNAs in
      separate constructs, and by controlling the ratio of the DNA amount for each
      subunit transfected we forced the cells to express GABAA receptors in a
      pharmacologically relevant form. A large batch of transfected human embryonic
      kidney 293 cells were cryopreserved and used to screen and evaluate GABAA
      modulators.In these cells, agonist activation of GABAA receptor resulted in Cl-
      efflux and membrane depolarization, which was detected by FLIPR as an increase in
      fluorescence signal. Based on our characterization of several known GABAA
      modulators and a test set of compounds known to bind to the GABAA benzodiazepine
      site, we have demonstrated the validity and utility of this assay for discovery
      of novel pharmacological agents acting at GABAA receptors.

PMID- 19090693
TI  - Noncovalent immobilization of enantioselective catalysts.

PMID- 19090694
TI  - Hope for the mammoth?

PMID- 19090695
TI  - Synergistic effects of mutations and nanoparticle templating in the self-assembly
      of cowpea chlorotic mottle virus capsids.
AB  - A study of the in vitro nanoparticle-templated assembly of a mutant of cowpea
      chlorotic mottle virus lacking most of the N-terminal domain (residues 4-37),
      NDelta34, is presented. Mutant empty proteins assemble into empty capsids with a
      much broader distribution of sizes than the wild-type virus. This increased
      flexibility in the assembly outcomes is known to be detrimental for the assembly
      process in the presence of molecular polyanions. However, when rigid polyanionic
      cores are used, such as nanoparticles, the assembly process is restored and virus
      like particles form. Moreover, the breadth of the nanoparticle-templated capsid
      size distribution becomes comparable with the wild-type virus size distribution.

PMID- 19090696
TI  - Tunable graphene dc superconducting quantum interference device.
AB  - Graphene exhibits unique electrical properties on account of its reduced
      dimensionality and "relativistic" band structure. When contacted with two
      superconducting electrodes, graphene can support Cooper pair transport, resulting
      in the well-known Josephson effect. We report here the fabrication and operation
      of a two junction dc superconducting quantum interference device (SQUID) formed
      by a single graphene sheet contacted with aluminum/palladium electrodes in the
      geometry of a loop. The supercurrent in this device can be modulated not only via
      an electrostatic gate but also by an applied magnetic fielda potentially powerful
      probe of electronic transport in graphene and an ultrasensitive platform for
      nanomagnetometry.

PMID- 19090698
TI  - Flinderoles A-C: antimalarial bis-indole alkaloids from Flindersia species.
AB  - With the aim of finding new natural product antimalarials, the novel indole
      alkaloids flinderole A-C were found to have selective antimalarial activities
      with IC(50) values between 0.15-1.42 microM. Flinderole A was isolated from the
      Australian plant Flindersia acuminata and flinderoles B and C from the Papua New
      Guinean plant F. amboinensis. Flinderoles A-C contain an unprecedented rearranged
      skeleton compared to their related isomers of the borreverine class of compounds.

PMID- 19090697
TI  - Photoluminescence, thermal transport, and breakdown in joule-heated GaN
      nanowires.
AB  - Thermal transport and breakdown in Joule-heated GaN nanowires is investigated
      using a combination of microphotoluminescence and in situ TEM characterization.
      The thermal conductivity of the nanowires is estimated to be <80 W/m.K, which is
      substantially below the bulk GaN value. Catastrophic breakdown in individual
      nanowires is observed to occur at a maximum temperature of approximately 1000 K,
      and nanowire morphology near the breakdown region indicates that failure occurs
      via thermal decomposition, a conclusion that is validated by in situ TEM images
      obtained during the failure process.

PMID- 19090699
TI  - Direct preparation of unsymmetrical difunctionalized cyclen derivatives by an Ugi
      multicomponent reaction.
AB  - A new and efficient synthetic protocol for the preparation of unsymmetrical
      difunctionalized cyclen and its close derivatives using a modified Ugi reaction
      (N-split Ugi) is described. The scope of this methodology is further extended by
      the successful use of various isocyanides, highly functionalized carboxylic
      acids, and aldehydes.

PMID- 19090701
TI  - Design, synthesis, and evaluation of biotinylated opioid derivatives as novel
      probes to study opioid pharmacology.
AB  - A generally applicable strategy of chemically labeling (-)-morphine (1) is
      described. The synthesis starts from commercially available starting materials
      and can be completed in two steps with an overall yield of 23%. In silico
      simulation and NMR results show that the binding of (-)-morphine to one of its
      molecular targets, toll-like receptor 4 (TLR4), was not affected by the
      modification. Secreted embryonic alkaline phosphatase (SEAP) reporter assay
      results demonstrate that C(3) biotinylated and unmodified (-)-morphine show
      similar biological activities in live cells. To our knowledge, these studies
      provide the first practical and concise method to label various opioid
      derivatives, a group of important therapeutics in pain management, for
      biochemical/pharmacological studies.

PMID- 19090703
TI  - 2008 American Society of Naturalists Awards: Sewall Wright Award - Spencer
      Barrett.

PMID- 19090700
TI  - Amine-reactive fluorene probes: synthesis, optical characterization,
      bioconjugation, and two-photon fluorescence imaging.
AB  - With the increasing demand for confocal and two-photon fluorescence imaging, the
      availability of reactive probes that possess high two-photon absorptivity, high
      fluorescence quantum yield, and high photostability is of paramount importance.
      To address the demand for better-performing probes, we prepared two-photon
      absorbing amine-reactive fluorenyl-based probes 2-(9,9-bis(2-(2
      methoxyethoxy)ethyl)-2-isothiocyanato-9H-fluoren-7-yl)benzothiazole (1) and 2-(4
      (2-(9,9-bis(2-(2-ethoxyethoxy)ethyl)-2-isothiocyanato-9H-fluoren-7
      yl)vinyl)phenyl)benzothiazole (2), incorporating the isothiocyanate as a reactive
      linker. Probe design was augmented by integrating high optical nonlinearities,
      increased hydrophilicity, and coupling with reactive functional groups for
      specific targeting of biomolecules, assuring a better impact on two-photon
      fluorescence microscopy (2PFM) imaging. The isothiocyanate (NCS) derivatives were
      conjugated with cyclic peptide RGDfK and Reelin protein. The study of the
      chemical and photophysical properties of the new labeling reagents, as well as
      the conjugates, is described. The conjugates displayed high chemical stability
      and photostability. The NCS derivatives had low fluorescence quantum yields,
      while their bioconjugates exhibited high fluorescence quantum yields, essentially
      "lighting up" after conjugation. Conventional and 2PFM imaging and fluorescence
      lifetime imaging (FLIM) of HeLa, NT2, and H1299 cells, incubated with two-photon
      absorbing amine-reactive probe (1), RGDfK-dye conjugate (7), and Reelin-dye
      conjugate (6), was demonstrated.

PMID- 19090704
TI  - 2008 American Society of Naturalists Awards: E. O. Wilson Award - Ulrich G.
      Mueller.

PMID- 19090706
TI  - Effects of survival on the attractiveness of cues to natal dispersers.
AB  - Habitat selection by natal dispersers is one of several contexts in which
      preexisting biases interact with experience to affect the attractiveness of cues
      from biologically significant items. Here we use a Bayesian approach to explore
      the conditions that favor this phenomenon. We demonstrate that the simplest
      possible type of natal experience--namely, survival to the age/stage of dispersal
      -can increase the attractiveness of cues from an individual's natal habitat
      relative to the attractiveness of those same cues to naive individuals. The
      effects of survivorship on cue attractiveness are strongest when the quality of
      the habitat that produces that cue varies widely across large spatial or temporal
      scales, when that type of habitat is rarely of high quality, and when offspring
      survivorship provides a reliable indication of the quality of that type of
      habitat at the current time and locality. More generally, the framework outlined
      here may also apply to other situations in which extended exposure to cues early
      in life increases the attractiveness of those cues later in life.

PMID- 19090707
TI  - Coordination and synchronization of vigilance in groups of prey: the role of
      collective detection and predators' preference for stragglers.
AB  - Prey living in groups often partly rely on companions to detect predators.
      Accordingly, individuals having vigilant neighbors could decrease their own
      vigilance, engendering a certain level of vigilance coordination in the group.
      However, when a predator attacks, individuals that spot it react quicker than
      individuals that follow them and have less chance of being targeted. Individuals
      with vigilant neighbors may then be particularly exposed, since they risk lagging
      behind their companions in an attack. Here, we incorporate this effect in a
      spatially explicit model of vigilance. A first version of the model derives the
      evolutionarily stable proportion of time allocated to vigilance for each position
      in the group. A second version considers the real alternation of feeding and
      vigilance and allows individuals to respond immediately when their neighbors
      raise their head or resume feeding. The model confirms then that the collective
      detection effect tends to coordinate vigilance. However, when predators display
      marked preferences for stragglers, adaptive response by prey generates waves of
      collective vigilance that may spread and circulate over the group. The overall
      level of vigilance in the group strongly oscillates, sometimes far away from the
      evolutionarily stable values, and the stabilizing effect of vigilance
      coordination is thwarted. These results illustrate real patterns of vigilance, in
      particular, the fact that group members often synchronize their vigilance.

PMID- 19090708
TI  - Enantioselective analysis of 2- and 3-hydroxy fatty acids in food samples.
AB  - 2-Hydroxy fatty acids (2-OH-FAs) and 3-hydroxy fatty acids (3-OH-FAs) were
      recently identified at trace levels in dairy products and other food samples
      (vegetable oils and animal brains). Due to the asymmetric carbon bearing the
      hydroxy group, they are chiral. This study focused on the enantioselective
      determination of 2- and 3-OH-FAs in food. For this purpose, extracted
      saponifiable lipids were converted into methyl esters, and the resulting fatty
      acid methyl esters (FAMEs) were separated into OH-FAMEs (minor fraction) and non
      OH-FAMEs (bulk fraction). OH-FAMEs were then derivatized with (R)-(-)-alpha
      methoxy-alpha-trifluoromethylphenylacetyl chloride [(R)-(-)-MTPA-Cl, Mosher's
      reagent] to produce the corresponding MTPA-O-FAMEs. MTPA-O-FAME diastereomers
      were then analyzed by gas chromatography with electron capture negative-ion mass
      spectrometry (GC/ECNI-MS) in the selected ion monitoring (SIM) mode. In the food
      samples, both (S)- and (R)-enantiomers of 2- and 3-OH-FAs were detected, with the
      (R)-enantiomer being enantiopure or predominant with one exception. Especially 2-
      and 3-OH-16:0 were found to contain relevant proportions of the (S)-enantiomer.
      The differences in enantiomeric composition of 2- and 3-OH-16:0 detected for
      cheese samples were proposed as markers for authenticity controls.

PMID- 19090709
TI  - Development of a rapid and confirmatory procedure to detect 17beta-estradiol 3
      benzoate treatments in bovine hair.
AB  - A high-performance liquid chromatography-tandem mass spectrometry method (LC
      MS/MS) was developed for efficient and confirmatory surveillance of illegal use
      of estradiol benzoate, even when this substance is used in reproductive control.
      After cryogenic grinding, estradiol benzoate was extracted from hair with
      acetonitrile for 24 h on a rocking table. The validation of the method was based
      on Commission Decision 2002/657/EC using the deuterated analogue of estradiol
      benzoate as internal standard. Decision limit (0.81 ng/g), detection capability
      (1.38 ng/g), repeatability CV% (13.7), within in laboratory reproducibility CV%
      (15.6%), and trueness (99.3%) were calculated. Using the proposed methodology the
      presence of estradiol benzoate in samples obtained from animals treated to
      synchronize their estrous cycles can be confirmed.

PMID- 19090710
TI  - Human colon and liver cancer cell proliferation inhibition by peptide
      hydrolysates derived from heat-stabilized defatted rice bran.
AB  - Rice bran, an economical, underutilized coproduct of rough rice milling, was used
      to produce peptide hydrolysates, which were investigated for anticancer activity.
      Protein hydrolysates prepared by Alcalase hydrolysis under optimized conditions
      were treated further to obtain gastrointestinal (GI)-resistant peptide
      hydrolysates. They were fractionated into >50, 10-50, 5-10, and <5 kDa sizes and
      evaluated for inhibitory activity on proliferation of human colon (Caco-2) and
      liver (HepG2) cancer cell lines by Trypan blue dye exclusion assay. GI-resistant
      <5 and 5-10 kDa sized peptide fractions inhibited growth of Caco-2 cells by 80%,
      and the <5 kDa fraction inhibited growth of HepG2 cells by approximately 50%
      compared to controls and nonresistant fractions. An MTS cell titer assay
      confirmed antiproliferative effects of the peptide fractions. The results
      demonstrated that 5-10 and <5 kDa sized GI-resistant fractions promoted
      significant (p < 0.05) inhibitory activities on both cancer cell lines compared
      to controls. More investigations are needed to show such value-added effects on
      the technofunctional and sensorial properties of the food protein and peptide
      matrices.

PMID- 19090711
TI  - Effect of different packaging films on postharvest quality and selected enzyme
      activities of Hypsizygus marmoreus mushrooms.
AB  - Freshly harvested Hypsizygus marmoreus mushrooms were packaged using different
      packaging films, and physiological changes associated with postharvest
      deterioration, together with the activities of selected enzymes thought to play a
      role in senescence, were monitored during subsequent storage for 16-24 days at 4
      degrees C and 65-70% relative humidity. A biaxially oriented polypropylene film
      (BOPP) maintained the postharvest appearance of the mushrooms most effectively by
      significantly reducing the incidence of unsightly aerial hyphae on the pileal
      surface and restricting mushroom softening. These samples also exhibited smaller
      initial decreases in soluble protein, smaller increases in reducing sugar
      content, and lower levels of malondialdehyde accumulation during early storage.
      Smallest increases in proteinase activity were recorded in samples wrapped with
      BOPP and polyoletin packaging, and superoxide dismutase and polyphenol oxidase
      levels were significantly higher and lower, respectively, in the former. Choice
      of packaging can significantly affect postharvest quality loss in H. marmoreus
      and improve mushroom shelf life.

PMID- 19090712
TI  - Distribution of bound hydroxycinnamic acids and their glycosyl esters in barley
      (Hordeum vulgare L.) air-classified flour: comparative study between reversed
      phase-high performance chromatography-mass spectrometry (RP-HPLC/MS) and
      spectrophotometric analysis.
AB  - The level of bound hydroxycinnamic acid was determined by spectrophotometry (as
      total hydroxycinnamic compounds and free-radical-scavenging activity) and
      reversed-phase high-performance chromatography (RP-HPLC) coupled to mass
      spectrometry (MS) in barley flours (whole meals and air-classified fractions:
      coarse fraction and fine fraction). Hydroxycinnamic acids and their derivatives
      were the main bound phenols in barley flours. A total of 12 different
      hydroxycinnamic acids were identified and quantified by HPLC/diode array detector
      (DAD)-MS within 90 min. Ferulic acid (as a simple and glycosylated derivative)
      was the main phenolic acid in barley flours, representing 89-93% of total
      hydroxycinnamic acids. The amount of total hydroxycinnamic acid in air-classified
      coarse fraction was 2 and 3 times higher than those of whole meal and the air
      classified fine fraction, respectively. Similarly, the coarse fraction showed
      higher antioxidant activity (650.03 micromol of TEAC/100 g of flour) compared to
      whole meal and the fine fraction (388.78 and 320.27 micromol of TEAC/100 g of
      flour, respectively).

PMID- 19090713
TI  - Comparison of 2-acetylfuran formation between ribose and glucose in the Maillard
      reaction.
AB  - Sugar type is a major factor regulating the reaction rates and pathways in
      Maillard reaction. Ribose and glucose were used to compare their reactivities and
      pathways of 2-acetylfuran formation. A stable isotope labeling method was used to
      study their reactivity. A 1:1 mixture of [(13)C(6)]glucose and unlabeled ribose
      (or other unlabeled sugar) was reacted with proline at 145 degrees C for 40 min.
      The reactivity of each sugar was revealed by the ratio of isotopomers. The
      reactivity of sugars in 2-acetylfuran formation decreased in the order ribose,
      fructose, glucose, rhamnose, and sucrose. This method simplified the reaction
      system and the calculation process and gave a direct comparison of reactivity as
      seen via mass spectrum. The difference between glucose and ribose in 2
      acetylfuran formation was that glucose could form 2-acetylfuran directly from
      cyclization of its intact carbon skeleton, whereas ribose first underwent
      degradation into fragments before forming a six-carbon unit leading to 2
      acetylfuran. In the presence of cysteine, ribose could not generate 2-acetylfuran
      at a detectable level. When ribose was reacted with glycine, formaldehyde
      generated from glycine combined with ribose to form 2-acetylfuran. In other amino
      acids, a symmetric structure of the ribose intermediate was formed, making
      fragmentation more complicated.

PMID- 19090714
TI  - Study of the lipidic and proteic composition of an industrial filmogenic yeast
      with applications as a nutritional supplement.
AB  - The lipid and protein contents of yeast strains that form "flor velum" during the
      aging of sherry wines have been studied during their fermentation and "velum"
      phases. The same analyses were carried out on two other strains that do not form
      velum (fermentative strains). The results show a high lipid content in velum
      yeast during its two phases. This strain changes its lipidic components while
      passing from the fermentative to the velum phase, with palmitic, palmitoleic, and
      stearic acid concentrations decreasing, while the oleic, behenic, and lignoceric
      acid concentrations increase. Furthermore, a higher proteic content can be seen
      during the filmogenic stage of velum yeast as compared to the fermentative stage
      of this strain. A well-balanced distribution of amino acids is observed, which
      includes all essential amino acids. The sulfurated amino acids are shown to be
      the most limited, and a high quantity of lysine has been detected. Finally, the
      values of PDCAAS (Protein Digestibility Corrected Amino Acid Score) and MEAA
      (Modified Index of Essential Amino Acids) of this strain make it recommendable
      for dietary uses.

PMID- 19090715
TI  - Exploring the pathogenesis of renal cell carcinoma: pathway and bioinformatics
      analysis of dysregulated genes and proteins.
AB  - We recently identified a group of proteins which are dysregulated in renal cell
      carcinoma (RCC). In this study, we performed bioinformatics and pathway analysis
      of these proteins. Proteins were mapped to gene ontology biological processes.
      The upregulated proteins tend to cluster in processes, such as cancer initiation
      and progression. In addition, we identified a number of pathways that are
      significantly enriched in RCC. Some of these are 'common' pathways which are
      dysregulated in many cancers, but we also identified a number of pathways which
      were not previously linked to RCC. In addition to their potential prognostic
      values, many of these pathways have a potential as therapeutic targets for RCC.
      To verify our findings, we compared our proteins to a pool of datasets from
      published reports. Although there were only a minimal number of common proteins,
      there was a significant overlap between the identified pathways in the two
      groups. Moreover, out of 16 individually discovered genes identified by a
      literature search, 10 were found to be related to our dysregulated pathways. We
      also verified the upregulation of the mammalian target of rapamycin signaling
      pathway in RCC by immunohistochemistry. Finally, we highlight the potential
      clinical applications of pathway analysis in kidney cancer.

PMID- 19090716
TI  - The influence of linoleic and linolenic acid on the activity and intracellular
      localisation of phospholipase D in COS-1 cells.
AB  - Phospholipase D (PLD) is a receptor-regulated signalling enzyme involved in
      biological functions, such as exocytosis, phagocytosis, actin dynamics, membrane
      trafficking, and is considered to be essential for stimulated degranulation of
      cells. The purpose of our investigation was to examine how the fatty acid pattern
      of cellular membranes influences the activities and cellular distribution of the
      PLD1 and PLD2 isoforms. Expression of GFP-tagged PLD1 and PLD2 in COS-1 cells
      that were stimulated with mastoparan after cultivation in 20 micromol linoleic
      (C18:2n6) or linolenic (C18:3n3) acid for 4 d demonstrated that PLD1 dramatically
      alters its cellular distribution and is redistributed from intracellular vesicles
      to the cell surface. PLD2, on the other hand, maintains its localisation at the
      plasma membrane. The activity of PLD, which corresponds to PLD1 and PLD2,
      significantly increased two- to three-fold in the presence of the fatty acids. We
      conclude that linoleic acid and linolenic acid supplementation affect the
      intracellular trafficking of the PLD1 isoform and the activity of PLD most likely
      due to alterations in the membrane lipid environment conferred by the fatty
      acids.

PMID- 19090717
TI  - Role of catalytic and non-catalytic subsite residues in ribonuclease activity of
      human eosinophil-derived neurotoxin.
AB  - Human eosinophil-derived neurotoxin (EDN), a secretory protein from eosinophils,
      is a member of the RNase A superfamily. The ribonucleolytic activity of EDN is
      central to its biological activities. EDN binds RNA in a cationic cleft, and the
      interaction between EDN and RNA substrate extends beyond the scissile bond. Based
      on its homology with RNase A, putative substrate binding subsites have been
      identified in EDN. The B1 and B2 subsites interact specifically with bases,
      whereas P0, P1, and P2 subsites interact with phosphoryl groups. In this study,
      we evaluated the role of putative residues of these subsites in the
      ribonucleolytic activity of EDN. We demonstrate that of the two base binding
      subsites, B1 is critical for the catalytic activity of EDN, as the substrate
      cleavage was dramatically reduced upon substitution of B1 subsite residues. Among
      the phosphate-binding subsites, P1 is the most crucial as mutations of its
      constituting residues totally abolished the catalytic activity of EDN. Mutation
      of P0 and P2 subsite residues only affected the catalytic activity on the
      homopolymer Poly(U). Our study demonstrates that P1 and B1 subsites of EDN are
      critical for its catalytic activity and that the other phosphate-binding subsites
      are involved in the activity on long homopolymeric substrates.

PMID- 19090718
TI  - A completed KLK activome profile: investigation of activation profiles of KLK9,
      10, and 15.
AB  - We previously reported the activation profiles of the human kallikrein-related
      peptidases (KLKs) as determined from a KLK pro-peptide fusion-protein system.
      That report described the activity profiles of 12 of the 15 mature KLKs versus
      the 15 different pro-KLK sequences. The missing profiles in the prior report,
      involving KLK9, 10, and 15, are now described. Sodium dodecyl sulfate
      polyacrylamide gel electrophoresis, mass spectrometry, and N-terminal sequence
      analyses show that KLK9 and 10 exhibit low hydrolytic activities towards all of
      the 15 pro-KLK sequences, while KLK15 exhibits significant activity towards both
      Arg- and Lys-containing KLK pro-sequences. The ability of KLK15 to activate pro
      KLK8, 12, and 14 is confirmed using recombinant pro-KLK proteins, and shown to be
      significant for activation of pro-KLK8 and 14, but not 12. These additional data
      for KLK9, 10, and 15 now permit a completed KLK activome profile, using a KLK pro
      peptide fusion-protein system, to be described. The results suggest that KLK15,
      once activated, can potentially feed back into additional pro-KLK activation
      pathways. Conversely, KLK9 and 10, once activated, are unlikely to participate in
      further pro-KLK activation pathways, although similar to KLK1 they may activate
      other bioactive peptides.

PMID- 19090719
TI  - Determination of three amino acids causing alteration of proteolytic activities
      of staphylococcal glutamyl endopeptidases.
AB  - Staphylococcus aureus, Staphylococcus epidermidis, and Staphylococcus warneri
      secrete glutamyl endopeptidases, designated GluV8, GluSE, and GluSW,
      respectively. The order of their protease activities is GluSE < GluSW << GluV8.
      In the present study, we investigated the mechanism that causes these
      differences. Expression of chimeric proteins between GluV8 and GluSE revealed
      that the difference is primarily attributed to amino acid residues 170-195, which
      define the intrinsic protease activity, and additionally to residues 119-169,
      which affect the proteolytic sensitivity. Among nine substitutions present in
      residues 170-195 of the three proteases, the substitutions at positions 185, 188,
      and 189 were responsible for the changes in their activities, and the combination
      of W185, V188, and P189, which naturally occurs in GluV8, exerts the highest
      protease activity. W185 and P189 were indispensable for full activity, but V188
      could be replaced by hydrophobic amino acids. These three amino acid residues
      appear to create a substrate-binding pocket together with the catalytic triad and
      the N-terminal V1, and therefore define the K(m) values of the proteases. We also
      describe a method to produce a chimeric form of GluSE and GluV8 that is resistant
      to proteolysis, and therefore possesses 4-fold higher activity than the wild-type
      recombinant GluV8.

PMID- 19090720
TI  - Genetic characterization of antibiotic resistance genes linked to class 1 and
      class 2 integrons in commensal strains of Escherichia coli isolated from poultry
      and swine.
AB  - The aim of this research was to identify the presence of integrons among
      Escherichia coli strains isolated from poultry and swine and to characterize the
      topological association of these integrons with resistance genes and assess their
      potential ability to transfer these elements by conjugation. One hundred and
      seventy-two strains of E. coli were isolated. Their resistance to tetracycline,
      streptomycin, sulfamethoxazole-trimethoprim, ciprofloxacin, and enrofloxacin was
      studied by plate dilution. In resistant strains the presence of integrons and
      resistance genes was assessed by PCR. In the variable region, genes aadA1, dfrA1,
      and qnr were analyzed. Also, presence of tetA, tetB, and sul1 was assessed.
      Transference of these genes and integrons in vitro was evaluated by conjugation
      assays, using E. coli J53 Az(r) as recipient strain. Seventy-eight percent and
      83% of the poultry and swine strains, respectively, were resistant to at least
      one of the studied antimicrobials. Of the isolated strains 91 presented
      integrons. Resistance genes detected within the integrons were aadA1, dfrA1, and
      sat1. Gene qnr was not detected. Genes tet and sul1 were identified in 105 and 53
      strains, respectively. Seven strains transferred their resistance determinants by
      conjugation. The results verify the high percentage of antibiotic resistance in
      the E. coli strains isolated, and these represent a reservoir of resistance genes
      and integrons.

PMID- 19090721
TI  - Molecular analysis of isoniazid resistance in different genotypes of
      Mycobacterium tuberculosis isolates from Iran.
AB  - Considering the significant increase of isoniazid (INH) resistance in Iranian
      Mycobacterium tuberculosis isolates in the last few years and to investigate the
      prevalence and diagnostic potential of the most commonly reported mutations
      associated with INH resistance in Iran, we analyzed parts of the katG gene and
      fabG1-inhA and oxyR-ahpC regulatory regions in a sample of 48 INH-resistant and
      25 INH-sensitive isolates. Mutations in the katG 315, fabG1-inhA, and oxyR-ahpC
      regulatory regions were detected in 58.3%, 18.7%, and 39.6% of isolates,
      respectively. The R463L polymorphism in the katG gene and the ahpC46A were
      detected with high frequency in both INH-resistant and -sensitive isolates.
      Spoligotyping and IS6110-based restriction fragment length polymorphism patterns
      revealed that most of the isolates containing ahpC46A and katG 463Leu
      polymorphism belonged to the Central Asian (CAS) super family. The tight
      relationship between ahpC46A and katG 463Leu polymorphisms and the CAS super
      family highlights the importance of the CAS super family in INH resistance in
      Iran. In conclusion, mutations at katG codon 315 or the fabG1-inhA regulatory
      region were identified in 77.0% of the INH-resistant isolates and in none of the
      INH-sensitive strains, and are highly predictive of isonizid resistance in
      Iranian isolates.

PMID- 19090723
TI  - Antimicrobial susceptibility pattern of Edwardsiella ictaluri isolates from
      natural outbreaks of bacillary necrosis of Pangasianodon hypophthalmus in
      Vietnam.
AB  - The purpose of this study was to assess the in vitro susceptibility of 64
      Vietnamese isolates of Edwardsiella ictaluri, the causal agent of the infectious
      disease Bacillus Necrosis Pangasius in Pangasianodon hypophthalmus, using the
      agar dilution technique. All isolates originated from different farms and were
      collected between 2002 and 2005. None of the isolates displayed acquired
      resistance to amoxicillin, amoxicillin-clavulanic acid, chloramphenicol,
      florfenicol, gentamicin, kanamycin, neomycin, and nitrofurantoin. Acquired
      resistance to streptomycin was detected in 83%, to oxytetracycline in 81%, and to
      trimethoprim in 71% of the isolates, as indicated by a bimodal distribution of
      the minimal inhibitory concentrations (MICs) of these antimicrobials. The MICs of
      enrofloxacin displayed a monomodal distribution with tailing toward the higher
      MIC values, possibly indicating reduced susceptibility of a minority of isolates
      (3 out of the 64). For the quinolone antimicrobial agents flumequin and oxolinic
      acid, acquired resistance was encountered in 8% and 6% of the strains,
      respectively. All strains were intrinsically resistant to the polypeptide
      antimicrobial agent colistin. Seventy-three percent of the isolates were shown to
      have acquired resistance to at least three antimicrobial agents. The results of
      this study emphasize the strict need to control both the prophylactic and
      curative use of antimicrobial agents in Vietnamese aquaculture.

PMID- 19090722
TI  - Genotype and antibiotic susceptibility patterns of drug-resistant Pseudomonas
      aeruginosa and Acinetobacter baumannii isolates in Taiwan.
AB  - Rapid and accurate identification of the drug susceptibility profile of clinical
      strains is very important for controlling bacterial infections and determining
      the antibiotic therapy. The objective of this study was to investigate the
      spectrum of the correlation between phenotypic and genetic characters of the drug
      resistant clinical isolates. A total of 133 clinical isolates, including 76
      Acinetobacter baumannii and 57 Pseudomonas aeruginosa, were examined for their
      antibiotic susceptibility by the method of disc diffusion. Among them, most of
      the isolates were multiresistant, and 80% of the strains showed phenotypic
      resistance to beta-lactam antibiotics. Using PCR analysis, among the several
      types of beta-lactamases, TEM was the most prevalent, and OXA was the second most
      prevalent. The integron harbored was identified by conserved segment PCR, and 50%
      of the test isolates carried integrons with various gene cassette sizes inserted.
      The results obtained from this study reveal that the majority of these isolates
      displayed multiple drug resistance phenotypes that were associated with their
      mutational gene profiles.

PMID- 19090725
TI  - Regulation of phosphoenolpyruvate carboxylase in PVY(NTN)-infected tobacco
      plants.
AB  - The effect of viral infection on the regulation of phosphoenolpyruvate
      carboxylase (PEPC, EC 4.1.1.31) in Nicotiana tabacum L. leaves was studied. PEPC
      activity was 3 times higher in infected plant leaves compared to healthy plants.
      Activity of plant PEPC can be regulated, e.g., by de novo synthesis or reversible
      phosphorylation. The reason for the increase of PEPC activity as a consequence of
      PVY(NTN) infection was studied. The amount of PEPC determined by Western blot
      analysis or by relative estimation of PEPC mRNA by real-time PCR did not differ
      in control and PVY(NTN)-infected plants. Changes in posttranslational
      modification of PEPC by phosphorylation were evaluated by comparing activity of
      the native and the dephosphorylated enzyme. The infected plants were
      characterized by a higher decrease of the enzyme activity after its
      dephosphorylation, which indicated a higher phosphorylation level. Immunochemical
      detection of phosphoproteins by Western blot analysis showed a more intensive
      band corresponding to PEPC from the infected material. This strengthens the
      hypothesis of an infection-related phosphorylation, which could be part of the
      plant's response to pathogen attack. The physiological implications of the
      increase in PEPC activity during PVY(NTN) infection are discussed.

PMID- 19090724
TI  - Interaction of the porcine reproductive and respiratory syndrome virus
      nucleocapsid protein with the inhibitor of MyoD family-a domain-containing
      protein.
AB  - Porcine reproductive and respiratory syndrome (PRRS) virus is an RNA virus that
      replicates in the cytoplasm, but the viral nucleocapsid (N) protein localizes
      specifically in the nucleus and nucleolus of virus-infected cells. Nuclear
      localization of N is non-essential for PRRSV replication in cultured cells but
      has been shown to modulate the pathogenesis of virus in pigs, suggesting that N
      plays an accessory role in the nucleus during infection. We identified by yeast
      two-hybrid screening the inhibitor of MyoD family-a (I-mfa) domain-containing
      protein (HIC) as a cellular partner for PRRS virus (PRRSV) N protein. This
      protein is a homolog of human HIC, a recently identified cellular transcription
      factor. The specific interaction of PRRSV N with HIC was confirmed in cells by
      mammalian two-hybrid assay and co-immunoprecipitation and in vitro by GST pull
      down assay. HIC is a zinc-binding protein and confocal microscopy demonstrated co
      localization of N with the HIC-p40 isomer in the nucleus and nucleolus, and in
      the cytoplasm with HIC-p32, which is the N-terminal truncation of HIC-p40. The
      porcine homolog of HIC is universally expressed in pig tissues including alveolar
      macrophages. The interaction of viral capsid with the cellular transcription
      factor implicates a possible regulation of host cell gene expression by the N
      protein during PRRSV infection.

PMID- 19090726
TI  - Human CYP4Z1 catalyzes the in-chain hydroxylation of lauric acid and myristic
      acid.
AB  - Overexpression of human CYP4Z1, a cytochrome P450 enzyme, has been correlated
      with poor prognosis in human cancer. However, its catalytic properties are not
      yet known. We expressed this P450 in Schizosaccharomyces pombe and demonstrate by
      whole-cell biotransformation assays CYP4Z1-dependent in-chain hydroxylation of
      lauric and myristic acid, which in both cases leads to the formation of four
      different monohydroxylated products at positions omega-2, omega-3, omega-4, and
      omega-5, respectively. The CYP4Z1-expressing fission yeast should be a new
      valuable tool for testing cancer drugs or for the development of new prodrug
      strategies.

PMID- 19090727
TI  - Expression and localization of atypical PKC isoforms in liver parenchymal cells.
AB  - Members of all three classes of the protein kinase C (PKC) family including
      atypical PKCzeta (PKCzeta) are involved in central functions of liver parenchymal
      cells. However, expression and localization of PKCiota (PKCiota), the highly
      homologous atypical PKC (aPKC) isoform, in hepatocytes is unknown to date.
      PKCzeta and PKCiota were cloned from human and rat liver and fused to fluorescent
      protein tags (YFP). The sequence of full-length rat PKCiota is not yet known and
      was cloned from cDNA of hepatocytes by the use of degenerated primers. PKCzeta
      YFP and PKCiota-YFP (human and rat) were expressed in HeLa or HEK293 cells and
      used to test the specificity of seven aPKC antibodies. Two antibodies were
      PKCiota-specific and two were specific for PKCzeta in immunofluorescence and
      Western blot analysis. Subcellular localization was analyzed by
      immunofluorescence in isolated rat and human hepatocytes and liver sections. Low
      immunoreactivity for aPKCs was found at the sinusoidal membrane and in the
      cytosol. The highest density of PKCiota as well as PKCzeta was found at the
      canalicular membrane in co-localization with ABC-transporters, such as bile salt
      export pump or multidrug resistance-associated protein 2. This topology suggests
      a specific function of aPKCs at the canalicular membrane in addition to their
      known role in cell polarity of epithelial cells.

PMID- 19090728
TI  - The assembly and activation of kinin-forming systems on the surface of human U
      937 macrophage-like cells.
AB  - A complex of three plasma proteins, including the high molecular mass kininogen
      (HK), prekallikrein (PK), and factor XII (FXII), is known to assemble on cell
      surfaces to release bradykinin-related proinflammatory peptides (kinins). Only
      recently, the binding of HK to human macrophages was described in the U-937 cell
      line model. In the present study, the adsorption of the other components of
      plasma kinin-generating system to these cells was characterized. FXII was found
      to tightly bind to U-937 cells and was also shown to partially compete with HK
      for the same binding sites on the macrophage surface. The Mac-1 and gClqR
      proteins were found to be receptors for FXII on the cell surface. PK indirectly
      docked to the macrophages via the cell-bound HK and FXII. Within the complex of
      these proteins assembled on the macrophage, PK could be activated by FXII/FXIIa
      or independently of this factor, and the active PK effectively released kinins
      from HK. The cell surface-bound HK could also be the substrate for tissue
      kallikrein approaching the cell from the bulk fluid. The kinins released at the
      surface are suggested to induce secondary responses in the macrophages, leading
      to further propagation of the inflammatory state.

PMID- 19090731
TI  - Using genetic information for the identification, classification and treatment of
      Crohn's disease: are we there yet?

PMID- 19090733
TI  - Lubiprostone for constipation and irritable bowel syndrome with constipation.
AB  - Chronic constipation and irritable bowel syndrome are heterogeneous disorders
      characterized by altered bowel habits, abdominal discomfort and/or difficult
      defecation. These conditions have a significant impact on patients' quality of
      life, as well as on the US economy, both in terms of healthcare costs and lost
      productivity. Treatment typically begins with lifestyle changes, increased fiber
      intake and osmotic and stimulant laxative intake. However, treatments for
      constipation vary in terms of their efficacy and safety. Furthermore, surveys of
      physicians and patients have revealed a strong desire for improved therapeutic
      options. Lubiprostone is a synthetic bicyclic fatty acid that is gut selective
      and stimulates type 2 chloride channels, resulting in increased chloride, sodium
      and water secretion into the lumen. The increased fluid secretion causes luminal
      distension, secondary peristalsis and laxation. Randomized Phase III trials have
      shown that lubiprostone is efficacious in the treatment of chronic idiopathic
      constipation and irritable bowel syndrome with constipation. The US FDA has
      approved lubiprostone at a dose of 24 microg twice daily for the treatment of
      chronic idiopathic constipation in adults, and at a dose of 8 microg twice daily
      for irritable bowel syndrome with constipation in adult women. Nausea, diarrhea
      and headaches are the most commonly reported side effects. In long-term studies,
      lubiprostone appears to be safe.

PMID- 19090734
TI  - Antiflagellin antibodies suggest infective participation in irritable bowel
      syndrome pathogenesis.
AB  - Irritable bowel syndrome (IBS) is a functional disorder of multifactorial origin.
      Recent attention has been paid to the potential role of immune activation in
      intestinal sensorimotor dysfunction and symptom generation in patients with IBS.
      The link between immune activation and IBS is further supported by the evidence
      that IBS may develop after an acute episode of infectious gastroenteritis, IBS
      like symptoms may precede the diagnosis or accompany a period of remission of
      inflammatory bowel disease (IBD), and quantitative histopathologic data
      demonstrate the presence of low-grade mucosal immune infiltration in a large
      subset of patients with IBS. These data also suggest some areas of potential
      overlap between IBS and IBD. The present study explored the possibility that,
      similarly to IBD patients, IBS patients have antibodies directed against certain
      components of indigenous flora, such as flagellin (the primary structural
      component of bacterial flagella). The authors demonstrated that, compared with
      healthy controls, antibodies against flagellin were recognized more frequently in
      patients with IBS. Furthermore, these antibodies were found more frequently in
      postinfectious compared with unspecific IBS. In patients with Crohn's disease,
      antiflagellin antibodies were detected with an increased frequency and at higher
      concentrations than in patients with IBS. All together, these results indicated
      the presence of a systemic immune activation in IBS patients, characterized by
      specific antibodies directed against luminal bacterial antigens. Furthermore,
      these results support the hypothesis that a subset of IBS presents an immune
      activation with pathogenic features common with IBD.

PMID- 19090736
TI  - New concepts in the pathogenesis of alcoholic liver disease.
AB  - Alcoholic liver disease still represents an important cause for death and
      disability in most well-developed countries and is becoming a leading cause of
      disease in developing countries. It is now increasingly clear that, besides the
      formation of acetaldehyde, alcohol effects on the liver include oxidative stress,
      disturbances in methionine metabolism, endoplasmic reticulum stress,
      inflammatory/immune responses and adipokine imbalances. This article will discuss
      the most recent findings on the mechanisms by which alcohol abuse causes hepatic
      steatosis and steatohepatitis, and now it contributes to the progression of
      fibrosis. Although still incomplete, these data shed new light on the
      multifactorial pathogenesis of alcoholic liver disease and open new possibilities
      in the understanding of how gender and genetic factors can influence disease
      progression.

PMID- 19090735
TI  - Immune modulation in gastrointestinal disorders: new opportunities for
      therapeutic peptides?
AB  - Inflammation is the response of vascularized tissues to injury, irritation and
      infection. Nearly always, the inflammatory response is successfully resolved and,
      when necessary, a process of wound healing is initiated. Nowhere in the body is
      this homeostatic process more challenging than in the gastrointestinal (GI)
      tract, where the microbial flora sits in very close proximity to the mucosal
      immune system, separated only by an epithelial cell barrier. Delicate regulatory
      systems of the mucosal immune system determine mucosal permeability and response
      to bacterial flora, and aberrations in this system result in acute or chronic
      inflammatory conditions. Examples of such are two commonly occurring inflammatory
      GI disorders: inflammatory bowel disease and postoperative ileus. Inflammatory
      bowel disease is the result of a chronic and excessive mucosal immune response,
      whereas postoperative ileus represents a transient condition of GI tract
      paralysis that is the result of an inflammatory response to abdominal surgery.
      The clinical management of both conditions is very challenging and depends
      heavily on the possibility of modulating the host immune response. In this brief
      report, we highlight the role of neuropeptides in GI physiology and immune
      regulation, discuss a recently discovered endogenous anti-inflammatory pathway
      mediated by the ChemR23 receptor and speculate on the therapeutic potential of
      peptides that bind G-protein-coupled receptors in the management of inflammation
      in the GI tract.

PMID- 19090737
TI  - Evidence-based diagnosis and locoregional therapy for hepatocellular carcinoma.
AB  - Early identification of hepatocellular carcinoma (HCC) is crucial to improving
      the results of therapy and for patients to be eligible for liver transplantation.
      Recent advances in noninvasive imaging technology include various techniques of
      harmonic ultrasound, new ultrasound contrast agents, multislice helical computed
      tomography and rapid high-quality magnetic resonance. The imaging diagnosis
      relies on the hallmark of arterial hypervascularity with portal venous washout.
      Since the use of better radiological techniques has improved the accuracy of
      noninvasive diagnosis, the role of liver biopsy in the diagnosis of HCC has
      declined. With recent advances in genomics and proteomics, a great number of
      potential markers have been identified and developed as new candidate markers for
      HCC. Locoregional therapies currently constitute the best options for early
      nonsurgical treatment of HCC. Percutaneous ethanol injection shows similar
      results to resection surgery for single tumors less than 3 cm in diameter.
      Radiofrequency ablation is superior to percutaneous ethanol injection in terms of
      local recurrence. Transarterial chemoembolization is currently the most common
      approach for the management of HCC without curative options since it improves
      patient survival, but the optimal embolizing agent, length of interval between
      sessions and whether the chemotherapeutic agent has any effect have not yet been
      determined. Combining transarterial chemoembolization with antiangiogenic agents,
      as well as with other techniques, such as radiofrequency ablation, may improve
      the results. Injection of radioisotopes such as yttrium-90, via the hepatic
      artery, may be particularly useful in patients with portal vein thrombosis.
      Comparisons with other transarterial techniques are needed.

PMID- 19090738
TI  - Management options for minimal hepatic encephalopathy.
AB  - Minimal hepatic encephalopathy (MHE) is a neurocognitive dysfunction that is
      present in the majority of patients with cirrhosis. MHE has a characteristic
      cognitive profile that cannot be diagnosed clinically. This cognitive dysfunction
      is independent of sleep dysfunction or problems with overall intelligence. MHE
      has a significant impact on quality of life, the ability to function in daily
      life and progression to overt hepatic encephalopathy. Driving ability can be
      impaired in MHE and this may be a significant factor behind motor vehicle
      accidents. A crucial aspect of the clinical care of MHE patients is their driving
      history, which is often ignored during routine care and can add a vital dimension
      to the overall disease assessment. Driving history should be an integral part of
      the care of patients with MHE. The preserved communication skills and lack of
      specific signs and insight make MHE difficult to diagnose. The predominant
      strategies for MHE diagnosis are psychometric or neurophysiological testing.
      These are usually limited by financial, normative or time constraints. Studies
      into inhibitory control, cognitive drug research and critical flicker frequency
      tests are encouraging. These tests do not require a psychologist for
      administration and interpretation. Lactulose and probiotics have been studied for
      their potential use as therapies for MHE, but these are not standard-of-care
      practices at this time. Therapy can improve the quality of life in MHE patients
      but the natural history, specific diagnostic strategies and treatment options are
      still being investigated.

PMID- 19090739
TI  - Selective or targeted gene/drug delivery for liver tumors: advantages and current
      status of local delivery.
AB  - There are various disorders involving the liver. They include metabolic diseases,
      hepatitis, liver cirrhosis and cancer, the latter of which may be the most
      serious. Delivery of therapeutic genes or drugs should be targeted to either one
      of the following cells in the liver: hepatocytes, Kupffer cells and tumor
      endothelial cells, or to the tumor cells themselves. To maximize the therapeutic
      effect and minimize systemic toxicity or nontarget injuries, the sufficient
      amount or dose of genes or drugs should be specifically delivered to a target,
      with minimal exposure in their active forms to nontarget cells. There are diverse
      strategies to improve selective delivery or targeting efficiency. In this
      article, we present potential new therapeutic strategies and clinical
      developments for liver cancer, with a focus on the progress in the localized
      delivery of therapeutic agents using image-guided procedures.

PMID- 19090741
TI  - Colon cancer surveillance in inflammatory bowel disease patients: current and
      emerging practices.
AB  - Colorectal cancer (CRC) is a feared complication of inflammatory bowel disease
      (IBD). The cumulative probability of developing this malignancy is significantly
      higher than in the general population, making IBD the third highest risk
      condition for CRC. Since CRC is such a concerning complication, it should be no
      surprise that patients and physicians want to know what the most important risk
      factors are for its development, as well as potential strategies for reducing
      these risks. This article reviews the current practice and emerging technologies
      for detecting and preventing colon cancer in patients with IBD.

PMID- 19090743
TI  - Desorption electrospray ionization mass spectrometry for trace analysis of
      agrochemicals in food.
AB  - Desorption electrospray ionization (DESI) is applied to the rapid, in situ,
      direct qualitative and quantitative (ultra)trace analysis of agrochemicals in
      foodstuffs. To evaluate the potential of DESI mass spectrometry (MS) in toxic
      residue testing in food, 16 representative multiclass agricultural chemicals
      (pesticides, insecticides, herbicides, and fungicides) were selected (namely,
      ametryn, amitraz, azoxystrobin, bitertanol, buprofezin, imazalil, imazalil
      metabolite, isofenphos-methyl, malathion, nitenpyram, prochloraz, spinosad,
      terbuthylazine, thiabendazole, and thiacloprid). The DESI-MS experiments were
      performed using 3 microL of solution spotted onto conventional smooth
      poly(tetrafluoroethylene) (PTFE) surfaces, with examination by MS and tandem mass
      spectrometry (MS/MS) using an ion trap mass spectrometer. Optimization of the
      spray solvent led to the use of acetonitrile/water (80:20) (v/v), with 1% formic
      acid. Most of the compounds tested showed remarkable sensitivity in the positive
      ion mode, approaching that attainable with conventional direct infusion
      electrospray mass spectrometry. To evaluate the potential of the proposed
      approach in real samples, different experiments were performed including the
      direct DESI-MS/MS analysis of fruit peels and also of fruit/vegetable extracts.
      The results proved that DESI allows the detection and confirmation of traces of
      agrochemicals in actual market-purchased samples. In addition, MS/MS confirmation
      of selected pesticides in spiked vegetable extracts was obtained at absolute
      levels as low as 1 pg for ametryn. Quantitation of imazalil residues was also
      undertaken using an isotopically labeled standard. The data obtained were in
      agreement with those from the liquid chromatography mass spectrometry (LC-MS)
      reference method, with relative standard deviation (RSD) values consistently
      below 15%. The results obtained demonstrate the sensitivity of DESI as they meet
      the stringent European Union pesticide regulation requirements (maximum residue
      levels) for a large percentage of the studied compounds.

PMID- 19090745
TI  - Synthesis, molecular, and electronic structure of (eta(8)-C8H8)Ln(scorpionate)
      half-sandwich complexes: an experimental key to a better understanding of f
      element-cyclooctatetraenyl bonding.
AB  - Synthetic routes leading to two series of (eta(8)
      cyclooctatetraenyl)lanthanide(III) scorpionate "mixed sandwich" complexes are
      reported. The early lanthanide derivatives (COT)Ln(Tp) (Ln = Ce (1), Pr (2), Nd
      (3), Sm (4)) and (COT)Ln(Tp(Me2)) (Ln = Ce (5), Pr (6), Nd (7), Sm (8)) (COT =
      eta(8)-cyclooctatetraenyl, Tp = hydrotris(pyrazolyl)borate, Tp(Me2) =
      hydrotris(3,5-dimethylpyrazolyl)borate) were obtained by reacting the dimeric
      halide precursors [(COT)Ln(mu-Cl)(THF)]2 with K[Tp] or K[Tp(Me2)], respectively
      For the late lanthanide elements a different synthetic route was developed. The
      complexes (COT)Ln(Tp) (Ln = Er (9), Lu (10)) were made by the reaction of
      (Tp)LnCl2(THF)1.5 with equivalent amounts of K2C8H8. All new compounds were
      isolated as intensely colored crystalline materials and fully characterized by
      elemental analyses and spectroscopic methods. The molecular structures of 4, 5,
      and 8 were elucidated by X-ray diffraction. The optical spectra of compounds 2
      and 4-8 were run at room and low temperatures. From the spectra obtained, the
      underlying crystal field splitting patterns of complexes 2, 4, 6, and 7 were
      derived and simulated by fitting the free parameters of a phenomenological
      Hamiltonian. The parameters used allow the estimation of the crystal field
      strengths experienced by the Ln3+ central ions and the insertion of complexes 2,
      4, 6, and 7 into empiric nephelauxetic and relativistic nephelauxetic series.
      Besides, the experimentally oriented non-relativistic and relativistic molecular
      orbital schemes of compound 6 were set up and compared with the results of
      previous model calculations on [Ln(COT)2]-, Pa(COT)2, and U(COT)2.

PMID- 19090740
TI  - Advances in antifibrotic therapy.
AB  - Sustained progress in defining the molecular pathophysiology of hepatic fibrosis
      has led to a comprehensive framework for developing antifibrotic therapies.
      Indeed, the single greatest limitation in bringing new drugs to the clinical
      setting is a lack of clarity regarding clinical trial and treatment end points,
      not a lack of promising agents. A range of treatments, including those developed
      for other indications, as well as those specifically developed for hepatic
      fibrosis, are nearing or in clinical trials. Most are focused on attacking
      features of either hepatic injury and/or activated stellate cells and
      myofibroblasts, which are the primary sources of extracellular matrix (scar)
      proteins. Thus, features of injury and stellate cell activation provide a useful
      template for classifying these emerging agents and point to a new class of
      therapies for patients with fibrosing liver disease.

PMID- 19090744
TI  - Multichannel monolithic quartz crystal microbalance gas sensor array.
AB  - Multichannel Monolithic Quartz Crystal Microbalance (MQCM), in which an array of
      electrodes is fabricated on a monolithic quartz wafer, is a very attractive
      approach for miniaturization using Micro-Electro-Mechanical Systems(MEMS)
      technology for high throughput chemical or biological sensor systems. In this
      paper, we demonstrate and validate a monolithic QCM sensor array for gas
      detections. The monolithic QCM sensor array chip was fabricated using a simple,
      straightforward method. Four pairs QCM electrodes on a single AT-cut 10 MHz
      quartz plate were fabricated in both symmetric and asymmetric designs. Their
      resonance and sensing properties were thoroughly characterized and compared with
      a single regular QCM under the same conditions by using parallel multichannel QCM
      instruments. It is confirmed that each QCM in the MQCM behaves like an
      independent oscillator that responds to mass and/or viscosity change. Various
      factors that may affect the MQCM performance, such as the fabrication design, the
      numbers of oscillated electrodes in one MQCM, and the concentration of target
      analytes, were studied. Finally, the MQCM electrodes were selectively coated with
      an assortment of sensing films (ionic liquids (BMICS, BMIBF(4)) and conductive
      polymer poly(vinyl ferrocene) (PVF)). Their applications capabilities for
      classification and detection of Volatile Organic Compounds (VOCs, i.e., ethanol,
      CH(2)Cl(2), hexane) and water were studied. Our results show that the single
      chip, multichannel QCM is a feasible and promising technology for a miniaturized,
      highly sensitive multianalysis system that can lead to substantial reductions in
      cost, analysis time, and sample volume.

PMID- 19090746
TI  - Flash pyrolysis of ethyl, n-propyl, and isopropyl iodides as monitored by
      supersonic expansion vacuum ultraviolet photoionization time-of-flight mass
      spectrometry.
AB  - The thermal decomposition of ethyl and propyl iodides, along with select
      isotopomers, up to 1300 K was performed by flash pyrolysis with a 20-100 mus time
      scale. The pyrolysis was followed by supersonic expansion to isolate the reactive
      intermediates and initial products, and detection was accomplished by vacuum
      ultraviolet single photon ionization time-of-flight mass spectrometry (VUV-SPI
      TOFMS). The products monitored, such as CH(3), CH(3)I, C(2)H(5), C(2)H(4), HI, I,
      C(3)H(7), C(3)H(6), and I(2), provide for the simultaneous and direct observation
      of molecular elimination and bond fission pathways in ethyl and propyl iodides.
      In the pyrolysis of ethyl iodide, both C-I bond fission and HI molecular
      elimination pathways are competitive at the elevated temperatures, with C-I bond
      fission being preferred; at temperatures >or=1000 K, the ethyl radical products
      further dissociate to ethene + H atoms. In the pyrolysis of isopropyl iodide,
      both HI molecular elimination and C-I bond fission are observed and the molecular
      elimination channel is more important at all the elevated temperatures; the
      isopropyl radicals produced in the C-I fission channel undergo further
      decomposition to propene + H at temperatures >or=850 K. In contrast, bond fission
      is found to dominate the n-propyl iodide pyrolysis; at temperatures >or=950 K the
      n-propyl radicals produced decompose into methyl radical + ethene and propene + H
      atom. Isotopomer experiments characterize the extent of surface reactions and
      verify that the HI molecular eliminations in ethyl and propyl iodides proceed by
      a C1, C2 elimination mechanism (the 1,2 intramolecular elimination).

PMID- 19090747
TI  - First-principles calculation of the isotope effect on boron nitride nanotube
      thermal conductivity.
AB  - Isotopic composition can dramatically affect thermal transport in nanoscale heat
      conduits such as nanotubes and nanowires. A 50% increase in thermal conductivity
      for isotopically pure boron ((11)B) nitride nanotubes was recently measured, but
      the reason for this enhancement remains unclear. To address this issue, we
      examine thermal transport through boron nitride nanotubes using an atomistic
      Green's function transport formalism coupled with phonon properties calculated
      from density functional theory. We develop an independent scatterer model for
      (10)B defects to account for phonon isotope scattering found in natural boron
      nitride nanotubes. Phonon scattering from (10)B dramatically reduces phonon
      transport at higher frequencies and our model accounts for the experimentally
      observed enhancement in thermal conductivity.

PMID- 19090749
TI  - Palladium-catalyzed gamma-selective and stereospecific allyl-aryl coupling
      between allylic acetates and arylboronic acids.
AB  - Allyl-aryl coupling between allylic acetates and arylboronic acids took place in
      the presence of catalytic amounts of Pd(OAc)(2), 1,10-phenanthroline, and
      AgSbF(6) with high gamma-selectivity and E/Z-selectivity. The reaction of an
      optically active allylic acetates with an alpha-stereogenic center proceeded with
      excellent alpha-to-gamma chirality transfer with syn-selectivity and gave the
      corresponding optically active allyl-aryl coupling products with a stereogenic
      center at the benzylic position.

PMID- 19090748
TI  - Characterizing antibody specificity to different protein morphologies by AFM.
AB  - Protein misfolding and aggregation can lead to several neurodegenerative diseases
      including Alzheimer's Disease (AD), Parkinson's Disease (PD) and Huntington's
      Disease (HD). While the respective proteins involved in each disease differ in
      their pathological effects and amino acid sequences, the aggregated forms all
      share a common cross beta-sheet conformation. Substantial controversy exists over
      the roles of the different aggregate morphologies in disease onset and
      progression, and analytical tools such as morphology specific antibodies are
      needed to distinguish between the different protein morphologies in situ. Here we
      utilize atomic force microscopy (AFM) to characterize the binding of three single
      chain antibody fragments (scFvs) to different morphologies of alpha-synuclein
      (alphaS). From the topographic images generated using the AFM, we were able to
      show that one scFv bound all morphologies of alphaS, a second bound only
      oligomeric alphaS, and a third bound only fibrillar alphaS by comparing the
      height distribution of the different alphaS morphologies with and without
      addition of the different scFvs. These results demonstrate the versatility of the
      AFM-based technique as an easy tool to characterize specific antigen-antibody
      binding and the potential applications of scFvs as promising immunodiagnostics
      for protein misfolding diseases.

PMID- 19090750
TI  - Structures of beta-amino ester enolates: new strategies using the method of
      continuous variation.
AB  - The solution structures of four enolates derived from beta-amino esters are
      investigated using (6)Li NMR spectroscopy in conjunction with the method of
      continuous variation (method of Job). Ensembles of homo- and heteroaggregated
      enolates are generated by mixing enantiomers of a single enolate (R/S mixtures),
      opposite antipodes of two different enolates (R/S' mixtures), and the same
      antipodes of two different enolates (R/R' mixtures). The numbers of observable
      aggregates and their dependence on the mole fraction of the two enolates confirm
      the hexamer assignments. Inherent symmetries observable in the (6)Li NMR spectra
      show the stereochemistry of chelation about the hexagonal drum.

PMID- 19090753
TI  - Evidence that graft-site candidiasis after kidney transplantation is acquired
      during organ recovery: a multicenter study in France.
AB  - BACKGROUND: Infections of renal grafts with Candida species can induce life
      threatening complications in the recipient. METHODS: A 9-year retrospective study
      involving all of the transplant centers in France was designed to determine the
      incidence, origin, characteristics, and outcome of graft-site candidiasis that
      occurred after kidney transplantation. Yeasts cultured from preservation or
      drainage solutions and graft specimens were recorded. RESULTS: Among 18,617
      kidney grafts, 18 recipients corresponding to 12 donors developed culture
      confirmed graft-site candidiasis (incidence, 1 case per 1000 grafts) a median of
      25 days after the graft procedure. Clinical presentations included 14 cases of
      renal arteritis (13 were complicated by aneurysm), 1 urinoma, 2 graft site
      abscesses, and 1 surgical site infection. Candida albicans was involved in 13
      cases. A unique C. albicans genotype or a single rare Candida species was
      involved in each episode. Together with the clinical history, these findings
      demonstrate that organ contamination followed by transmission to the recipient
      occurred during recovery. Therapeutic management varied from simple monitoring in
      1 case to a combination of surgery (nephrectomy in 9 cases and arterial bypass in
      9 cases) and antifungal therapy (14 cases). Overall, 3 of 18 kidney transplant
      recipients died, and 9 had their graft surgically removed. CONCLUSION: Graft
      transmitted candidiasis that ends most often in fungal arteritis is associated
      with high morbidity and mortality after kidney transplantation and is related to
      organ contamination during recovery in the donor.

PMID- 19090754
TI  - Water and salt distribution in Atlantic salmon (Salmo salar) studied by low-field
      1H NMR, 1H and 23Na MRI and light microscopy: effects of raw material quality and
      brine salting.
AB  - The effect of different Atlantic salmon raw materials (prerigor, postrigor and
      frozen/thawed) on water mobility and salt uptake after brine salting was
      investigated by using LF 1H NMR T2 relaxation,1H and 23Na MRI and light
      microscopy. Distributed exponential analysis of the T2 relaxation data revealed
      two main water pools in all raw materials, T21 and T22, with relaxation times in
      the range of 20-100 ms and 100-300 ms, respectively. Raw material differences
      were reflected in the T2 relaxation data. Light microscopy demonstrated
      structural differences between unsalted and salted raw materials. For prerigor
      fillets, salting induced a decrease in T21 population coupled with a more open
      microstructure compared to unsalted fillets, whereas for frozen/thawed fillets,
      an increase in T21 population coupled with salt-induced swelling of myofibers was
      observed. The result implies that the T21 population was directly affected by the
      density of the muscle myofiber lattice. MR imaging revealed significant
      differences in salt uptake between raw materials, prerigor salted fillets gained
      least salt (1.3-1.6% NaCl), whereas the frozen/thawed fillets gained most salt
      (2.7-2.9% NaCl), and obtained the most even salt distribution due to the more
      open microstructure. This study demonstrates the advantage of LF NMR T2
      relaxation and 1H and 23Na MRI as effective tools for understanding of the
      relationship between the microstructure of fish muscle, its water mobility and
      its salt uptake.

PMID- 19090755
TI  - Metabolism and pharmacokinetics of 3,3',4',7-tetrahydroxyflavone (fisetin), 5
      hydroxyflavone, and 7-hydroxyflavone and antihemolysis effects of fisetin and its
      serum metabolites.
AB  - 3,3',4',7-Tetrahydroxyflavone (fisetin) has shown various beneficial
      bioactivities. This study investigated the metabolism and pharmacokinetics of
      fisetin, 5-hydroxyflavone (5-OH-flavone), and 7-hydroxyflavone (7-OH-flavone) in
      male Sprague-Dawley rats. Blood was withdrawn via cardiopuncture and assayed by
      HPLC before and after hydrolysis with sulfatase and beta-glucuronidase. The
      results indicated that after intravenous administration of fisetin (10 mg/kg of
      bw), fisetin declined rapidly and fisetin sulfates/glucuronides emerged
      instantaneously. When fisetin (50 mg/kg of bw) was given orally, fisetin parent
      form was transiently present in serum only during the absorption phase, whereas
      fisetin sulfates/glucuronides predominated. The serum metabolites of fisetin
      showed less potent inhibition on 2,2'-azobis(2-amidinopropane hydrochloride)
      (AAPH)-induced hemolysis than fisetin. Following oral administrations of 40 mg/kg
      of bw of 5-OH-flavone and 7-OH-flavone, the glucuronide of 5-OH-flavone and the
      sulfate/glucuronide of 7-OH-flavone were found in serum, whereas no traces of
      parent forms were detected. In conclusion, fisetin and 7-OH-flavone were rapidly
      and extensively biotransformed into their sulfate/glucuronide, whereas 5-OH
      flavone was exclusively metabolized to glucuronide.

PMID- 19090756
TI  - Gas phase reactions of CH(3)(+) with a series of homo- and heterocyclic
      molecules.
AB  - In gas phase ion chemistry, the growth of larger molecules is known to occur
      through association of ions and neutrals. Where the ion attaches to the neutral
      is important because it can influence the possibility of additional associations,
      effectively enabling or terminating further molecular growth. This was
      investigated by using a Selected Ion Flow Tube (SIFT) at 300 K to study the
      reactions of CH(3)(+) with the following series of single-ring homocyclic and
      heterocyclic molecules: benzene (C(6)H(6)), cyclohexane (C(6)H(12)), pyridine
      (C(5)H(5)N), pyrimidine (C(4)H(4)N(2)), piperidine (C(5)H(11)N), 1,4-dioxane
      (C(4)H(8)O(2)), furan (C(4)H(4)O), pyrrole (C(4)H(5)N), and pyrrolidine
      (C(4)H(9)N). Most of the reactions, except for 1,4-dioxane, pyrrole, and
      pyrrolidine, proceed at the gas kinetic rate. In the ion product distributions,
      charge transfer, hydride ion abstraction, proton transfer, fragmentation, and
      association were observed. In particular, proton transfer is seen to be small in
      all cases even though these channels are energetically favorable. Association is
      appreciable when the molecules are aromatic (except for furan) and nonexistent
      when there are no pi electrons in the ring. CH(3)(+) ions are an important
      intermediate in molecular synthesis in interstellar clouds and in the Titan
      ionosphere and ring molecules have also been detected in these media. The
      significance of the studied reactions to these media is discussed.

PMID- 19090757
TI  - Beach dune sand hydrophobicity due to the presence of beach vitex ( Vitex
      rotundifolia L. f.).
AB  - Conservation and preservation concerns have led to efforts to understand
      mechanisms of invasiveness and the effects these mechanisms have on the
      environment. Vitex rotundifolia L. f. [beach vitex (BV)] was introduced as a salt
      tolerant woody ground cover, but it has since become invasive on primary and
      secondary dunes in coastal areas of the southeastern United States. Much of its
      invasive potential may be the result of intense substrate hydrophobicity
      underneath established stands, which is believed to prohibit seedling
      establishment by other plants including native plant species. This research was
      conducted to better understand BV-induced sand hydrophobicity by carrying out
      dune surveys of BV-infested areas of the South Carolina coast, identifying the
      compounds responsible for this activity via chemical analysis, and quantifying
      hydrophobicity persistence by resampling sites following removal of above-ground
      BV. The findings indicated that sand under BV cover was significantly
      hydrophobic, that cuticular alkanes from leaves and fruits were responsible for
      this hydrophobicity, and that extreme substrate hydrophobicity persisted for >3
      years following BV removal.

PMID- 19090758
TI  - Screening and identification of precursor compounds of dimethyl trisulfide (DMTS)
      in Japanese sake.
AB  - Dimethyl trisulfide (DMTS) is involved in the unpalatable aroma of stale sake,
      called "hineka"; however, the mechanism underlying the formation of DMTS during
      the storage of sake has not been elucidated. This paper investigates the
      precursors of DMTS in sake. An experiment using [methyl-d(3)]-methionine showed
      that Strecker degradation of methionine plays a minor role in the formation of
      DMTS. Separation of components in sake by cation exchange resin revealed that
      DMTS precursors are present in the acidic/neutral fraction rather than in the
      basic one. Purification of the DMTS precursor compounds was carried out through
      several chromatographic steps, measuring DMTS-producing potential as an index.
      High-resolution ESI-MS and 1D/2D NMR experiments enabled the identification of
      one of the precursor compounds as 1,2-dihydroxy-5-(methylsulfinyl)pentan-3-one.

PMID- 19090759
TI  - Time-course study and effects of drying method on concentrations of gamma
      aminobutyric acid, flavonoids, anthocyanin, and 2''-hydroxynicotianamine in
      leaves of buckwheats.
AB  - Concentrations of gamma-aminobutyric acid (GABA), rutin, minor flavonoids (such
      as orientin), anthocyanin, and 2''-hydroxynicotianamine (2HN) were quantified in
      the leaves of common and tartary buckwheat (Fagopyrum esculentum Moench and
      Fagopyrum tataricum Gaertn., respectively), at 14, 28, and 42 days after sowing
      (DAS). GABA and rutin concentrations peaked at 42 DAS, whereas anthocyain, 2HN,
      and minor flavonoid concentrations declined with the age of the plants. However,
      at 42 DAS, anthocyanin concentrations in the leaves of tartary buckwheat Hokkai
      T10 leaves were at least 10-fold greater than in the other buckwheats tested. In
      addition, the effects on target compound concentrations and 1,1-diphenyl-2
      picrylhydrazyl radical scavenging activity of three different drying methods (20
      h at 40 degrees C, 7 h at 70 degrees C, or lyophilization) were investigated. In
      general, the drying method had no significant effect on the parameters tested.
      These results indicate that, in terms of GABA, rutin, and anthocyanin
      concentrations, leaf powder from 42 day old Hokkai T10 has the potential to be a
      useful food ingredient, such as Ao-jiru juice.

PMID- 19090760
TI  - Organizational behavior: linking individuals and groups to organizational
      contexts.

PMID- 19090761
TI  - Organizational behavior: where we've been, where we're going.

PMID- 19090762
TI  - Practical model for imperfect conductometric molecular wire sensors.
AB  - We present a theoretical model for description of real polyreceptor molecular
      wire sensors (MWS), whose conductance signal may dramatically reduce upon analyte
      binding to one of the receptors coupled to the molecular wire but may not vanish
      as completely as assumed in the ideal MWS model. For the present nonideal MWS
      model, we establish the exact relationship between analyte concentration and the
      sensory signal intensity. It turns out that, whereas the Stern-Volmer curve of
      the ideal MWS always has a positive curvature, the Stern-Volmer curve of the
      imperfect MWS can have a negative curvature, consistent with experimental data.
      We find that the MWS still performs better than the corresponding ideal
      monoreceptor sensor, unless the nonideality of the imperfect MWS is egregiously
      large. We establish the conditions for the imperfect polyreceptor MWS to have a
      sensitivity and detection limit superior to the traditional monoreceptor sensor.

PMID- 19090763
TI  - Probing the magnetic exchange forces of iron on the atomic scale.
AB  - Applying magnetic exchange force microscopy with an Fe-coated tip, we
      experimentally resolve the atomic-scale antiferromagnetic structure of the Fe
      monolayer on W(001). On the basis of first-principles calculations, using an Fe
      nanocluster as a tip, we determine the distance dependence of the magnetic
      exchange forces. Significant relaxation of tip and sample atoms occurs, which
      depend sensitively on the local magnetic configuration. This shifts the onset of
      magnetic interactions toward larger separations and facilitates their
      observation. Implementing a multiatom tip in the calculations and accounting for
      relaxation effects are crucial to obtain the correct sign and distance dependence
      of the magnetic exchange interaction. By comparison with our calculations, we
      show that the experimentally observed contrast is due to a competition between
      chemical and magnetic forces.

PMID- 19090764
TI  - Peach ( Prunus persica L. Batsch) allergen-encoding genes are developmentally
      regulated and affected by fruit load and light radiation.
AB  - The fruits of Rosaceae species may frequently induce allergic reactions in both
      adults and children, especially in the Mediterranean area. In peach, true
      allergens and cross-reactive proteins may cause hypersensitive reactions
      involving a wide diversity of symptoms. Three known classes of allergenic
      proteins, namely, Pru p 1, Pru p 3, and Pru p 4, have been reported to be mostly
      involved, but an exhaustive survey of the proteins determining the overall
      allergenic potential, their biological functions, and the factors affecting the
      expression of the related genes is still missing. In the present study, the
      expression profiles of some selected genes encoding peach allergen isoforms were
      studied during fruit growth and development and upon different fruit load and
      light radiation regimens. The results indicate that the majority of allergen
      encoding genes are expressed at their maximum during the ripening stage,
      therefore representing a potential risk for peach consumers. Nevertheless,
      enhancing the light radiation and decreasing the fruit load achieved a reduction
      of the transcription rate of most genes and a possible decrease of the overall
      allergenic potential at harvest. According to these data, new growing practices
      could be set up to obtain hypoallergenic peach fruits and eventually combined
      with the cultivation of hypoallergenic genotypes to obtain a significant
      reduction of the allergenic potential.

PMID- 19090765
TI  - Effects of black carbon on pyrethroid availability in sediment.
AB  - Pyrethroids are widely used synthetic insecticides with the characteristics of
      high hydrophobicity and broad-spectrum aquatic toxicity. Many studies indicate
      that black carbon (BC) plays an important role in the bioavailability of
      hydrophobic compounds such as polycyclic aromatic hydrocarbons and
      polychlorinated biphenyls in soils and sediments. However, the effect of BC on
      bioavailability of other compounds such as pyrethroids in sediments is less
      known. In this study, we simultaneously measured pyrethroid uptake into
      polydimethylsiloxane (PDMS) fibers and 24 h bioaccumulation in Chironomus tentans
      in a sediment amended with a charcoal at different rates. There were significant
      negative correlations between the accumulation of pyrethroids in PDMS fibers
      (C(PDMS)) and the charcoal level in sediment. When the charcoal content was
      increased from 0 to 1.0%, C(PDMS) decreased by 5.7-9.1%. Amendment of 1.5%
      charcoal to the original sediment decreased biota sediment accumulation factor
      (BSAF) of (14)C-permethrin in C. tentans from 2.8 to 1.7. The effect of charcoal
      was further found to be similar for the different subcellular fractions of C.
      tentans, including cell debris, organelles and proteins, and granules. The
      overall effect of charcoal on pyrethroid availability, however, was modest, and
      adsorption of pyrethroids on pure charcoal was found to be similar to that on
      sediment organic carbon. The relatively weak sorption on charcoal was likely due
      to the large molecular weight and sizes of pyrethroids, which might hinder their
      diffusion into charcoal nanopores.

PMID- 19090766
TI  - Iron chelators of the dipyridylketone thiosemicarbazone class: precomplexation
      and transmetalation effects on anticancer activity.
AB  - We previously reported a series of di-2-pyridylketone thiosemicarbazone (HDpT)
      chelators that showed marked and selective antitumor activity (Whitnall, M.; et
      al. Proc. Natl. Acad. Sci. U.S.A. 2006, 103, 14901-14906). To further understand
      their biological efficacy, we report the characterization and activity of their
      Mn(II), Co(III), Ni(II), Cu(II), and Zn(II) complexes. The X-ray crystal
      structures of four divalent (Mn, Ni, Cu, and Zn) and one trivalent (Fe) complexes
      are reported. Electrochemistry shows the Fe(III/II) and Cu(II/I) potentials of
      the complexes may be redox-active within cells. Stability constants were also
      determined for the Mn(II), Ni(II), Cu(II), and Zn(II) complexes. All divalent
      complexes underwent transmetalation upon encountering Fe(II), to form low spin
      ferrous complexes. Importantly, the divalent Mn(II), Ni(II), Cu(II), and Zn(II)
      complexes of the HDpT analogues are equally active in preventing proliferation as
      their ligands, suggesting the complexes act as lipophilic vehicles facilitating
      intracellular delivery of the free ligand upon metal dissociation.

PMID- 19090767
TI  - Berberine analogues as a novel class of the low-density-lipoprotein receptor up
      regulators: synthesis, structure-activity relationships, and cholesterol-lowering
      efficacy.
AB  - Twenty-nine derivatives of berberine (1) or pseudoberberine (2) were designed,
      semisynthesized, and evaluated for their up-regulatory activity on the low
      density-lipoprotein receptor (LDLR) expression. SAR analysis revealed that (i)
      the methylenedioxy group at the 2- and 3-position is an essential element to keep
      the activity, (ii) the 7-position quaternary ammonium and planar structure of the
      compound are activity-required, and (iii) addition of electron-donating groups at
      the 7- or 13-position reduced the activity. Of the compound 1 analogues, compound
      2 exhibited an increased activity on LDLR expression compared to 1. In the
      hyperlipidemic rats, compound 2 (100 (mg/kg)/day) reduced blood CHO and LDL-c by
      42.6% and 49.4%, respectively, more efficient than 1 did (p < 0.01 for both). The
      results were confirmed in the hyperlipidemic mice. LD(50) of 2 in mice was over
      5000 mg/kg (oral). We consider compound 2 a promising cholesterol-lowering drug
      candidate.

PMID- 19090768
TI  - Nosocomial outbreak of Clostridium difficile-associated disease in a pediatric
      intensive care unit in Madrid.

PMID- 19090769
TI  - Lost in translation? Reliability of assessing inpatient antimicrobial
      appropriateness with use of computerized case vignettes.
AB  - OBJECTIVE: To describe and measure reliability of a computer-assisted method of
      case vignette assembly and expert review to assess the appropriateness of
      antimicrobial therapy for hospitalized adults. DESIGN: Feasibility and
      reliability analysis of computer-assisted tool used to compare the effects of
      antimicrobial stewardship interventions. SETTING: Public teaching hospital.
      PATIENTS: Randomly selected adult antimicrobial recipients admitted to inpatient
      medicine services. METHODS: Clinical data abstracted from 504 paper medical
      records were merged with computerized laboratory and pharmacy data to assemble
      case vignettes that underwent expert review for appropriateness. We performed 3
      validations, as follows: data for 35 vignettes abstracted independently by 2
      research assistants were assessed for interrater agreement, expert review of 24
      vignettes was compared with review of the corresponding paper medical records,
      and interrater reliability of antimicrobial appropriateness assessments by 2
      experts was determined for 70 case vignettes. RESULTS: Vignette assembly and
      expert review each required 10-12 minutes per case. Potentially important
      discrepancies occurred in 0%-32% of clinical findings abstracted independently by
      2 research assistants. Expert review of 24 vignettes and the corresponding full
      paper medical records yielded fair agreement (kappa, 0.30). The 2 experts
      identified inappropriate initial antimicrobial therapy in 67% and 61% of case
      vignettes reviewed independently; interrater agreement was improved after
      sequential case discussion and stringent application of appropriateness criteria
      (kappa, 0.72). CONCLUSIONS: Our case vignette assembly and expert review method
      is efficient, but improvements in both technical and human performance are needed
      to be able to yield valid estimates of the prevalence of inappropriate
      antimicrobial use. Assessments of antimicrobial appropriateness require
      validation.

PMID- 19090770
TI  - Determination of the efficacy of sterile barrier systems against microbial
      challenges during transport and storage.
AB  - OBJECTIVE: The sterility assurance level of 10(-6) is an established standard
      that defines the quality of sterile products. The aim of the present study was to
      develop a method that correlated the results from microbial-barrier testing of
      flexible sterile barrier systems with the estimated microbial challenge that the
      package encounters during storage and transport. METHODS: The effectiveness of
      microbial-barrier packaging was determined by the use of an exposure chamber test
      with 20 periodic atmospheric pressure changes of 50 and 70 hPa. Flexible peel
      pouches were used as sterile barrier systems. The logarithmic reduction value of
      a sterile barrier system was calculated on the basis of the experimental results
      and compared with the logarithmic reduction value required for the microbial
      challenges to maintain sterility during transport and storage. RESULTS: For
      pouches made of paper and plastic-film material, a logarithmic reduction value of
      5.4 was obtained on the basis of 30 of 99 plates becoming nonsterile after being
      exposed to a 50 hPa difference in periodic atmospheric pressure changes. For
      pouches made of paper and plastic-film material, a logarithmic reduction value of
      5.2 was obtained on the basis of 48 of 100 plates becoming nonsterile after being
      exposed to a 70 hPa difference in atmospheric pressure. For pouches made of
      nonwoven and plastic-film material, logarithmic reduction values of 6.38 (ie, 3
      of 99 plates became nonsterile after being exposed to a 50 hPa pressure
      difference) and 6.07 (ie, 3 of the 99 plates became nonsterile after being
      exposed to a 70 hPa pressure difference) were obtained. Calculating an expected
      microbial challenge during transport and storage that requires barrier properties
      corresponding to a logarithmic reduction value of 5.83 and taking the sterility
      assurance level into account, we found that only the nonwoven pouches fulfilled
      the European standard EN 556-1. CONCLUSIONS: Using the data obtained in a
      microbial exposure test with a specified flow rate of a bacterial aerosol, we
      found that the effectiveness of the sterile barrier system against the actual
      microbial challenge can be examined and evaluated at the sterility assurance
      level of 10(-6).

PMID- 19090771
TI  - Efficacy of combination of N-acetylcysteine, gentamicin, and amphotericin B for
      prevention of microbial colonization of ventricular assist devices.
AB  - We assessed the in vitro antimicrobial activity and the in vivo efficacy of
      dipping ventricular assist devices in a combination of N-acetylcysteine,
      gentamicin, and amphotericin B (NAC/G/A). Ventricular assist devices dipped in
      NAC/G/A exhibited broad-spectrum antimicrobial activity in vitro and were less
      likely than undipped devices to become colonized with Staphylococcus aureus in a
      rabbit model.

PMID- 19090772
TI  - How many species have mass M?
AB  - Within large taxonomic assemblages, the number of species with adult body mass M
      is characterized by a broad but asymmetric distribution, with the largest mass
      being orders of magnitude larger than the typical mass. This canonical shape can
      be explained by cladogenetic diffusion that is bounded below by a hard limit on
      viable species mass and above by extinction risks that increase weakly with mass.
      Here we introduce and analytically solve a simplified cladogenetic diffusion
      model. When appropriately parameterized, the diffusion-reaction equation predicts
      mass distributions that are in good agreement with data on 4,002 terrestrial
      mammals from the late Quaternary and 8,617 extant bird species. Under this model,
      we show that a specific trade-off between the strength of within-lineage drift
      toward larger masses (Cope's rule) and the increased risk of extinction from
      increased mass is necessary to produce realistic mass distributions for both
      taxa. We then make several predictions about the evolution of avian species
      masses.

PMID- 19090773
TI  - CD3zeta down-modulation may explain Vgamma9Vdelta2 T lymphocyte anergy in HIV
      infected patients.
AB  - The aim of the present study was to explain the observed anergy of Vgamma9Vdelta2
      T cells from human immunodeficiency virus (HIV)-positive patients. CD3zeta
      expression and interferon (IFN)-gamma production by Vgamma9Vdelta2 T cells from
      HIV-positive and HIV-negative subjects were analyzed. We demonstrated that
      Vgamma9Vdelta2 T cells from HIV-infected patients expressed a lower level of
      CD3zeta than did Vgamma9Vdelta2 T cells from healthy donors. A direct correlation
      was found between CD3zeta expression and IFN-gamma production capability by
      Vgamma9Vdelta2 T cells. However, activation of protein kinase C by phorbol
      myristate acetate is able to restore CD3zeta expression and IFN-gamma production.
      Our findings may contribute to clarification of the molecular mechanisms of
      Vgamma9Vdelta2 T cell anergy found in HIV-positive patients.

PMID- 19090774
TI  - Transmission of imported vaccine-derived poliovirus in an undervaccinated
      community in Minnesota.
AB  - BACKGROUND: Oral poliovirus vaccine (OPV) has not been used in the United States
      since 2000. Type 1 vaccine-derived poliovirus (VDPV) was identified in September
      2005, from an unvaccinated Amish infant hospitalized in Minnesota with severe
      combined immunodeficiency. An investigation was conducted to determine the source
      of the virus and its means of transmission. METHODS: The infant was tested
      serially for poliovirus excretion. Investigations were conducted to detect
      poliovirus infections or paralytic poliomyelitis in Amish communities in
      Minnesota, neighboring states, and Ontario, Canada. Genomic sequences of
      poliovirus isolates were determined for phylogenetic analysis. RESULTS: No source
      for the VDPV could be identified. In the index community, 8 (35%) of 23 children
      tested, including the infant, had evidence of type 1 poliovirus or VDPV
      infection. Phylogenetic analysis suggested that the VDPV circulated in the
      community for approximately 2 months before the infant's infection was detected
      and that the initiating OPV dose had been given before her birth. No paralytic
      disease was found in the community, and no poliovirus infections were found in
      other Amish communities investigated. CONCLUSIONS: This is the first demonstrated
      transmission of VDPV in an undervaccinated community in a developed country.
      Continued vigilance is needed in all countries to identify poliovirus infections
      in communities at high risk of poliovirus transmission.

PMID- 19090776
TI  - Unmasked tuberculosis and tuberculosis immune reconstitution inflammatory
      disease: a disease spectrum after initiation of antiretroviral therapy.
AB  - Antiretroviral therapy (ART) has beneficial effects on mortality and lowers the
      incidence of diseases caused by opportunistic infections, such as tuberculosis
      (TB). Although ART has sustained long-term benefits, the risk of TB is high
      during the first 3 months after ART initiation. Among cases of ART-associated TB,
      we define "unmasked TB" as that which occurs in patients with reactivation
      disease who develop clinically recognizable TB after ART with the restoration of
      previously acquired TB antigen-specific functional immune responses. TB cases
      with clinical evidence of an inflammatory syndrome are a subset of these unmasked
      cases, which we define as "unmasked TB-immune reconstitution inflammatory
      syndrome." With more widespread use of ART in areas with a high prevalence of TB,
      unmasked TB will likely become more common. TB diagnostics with improved
      sensitivity and specificity are urgently needed to detect subclinical TB before
      it is unmasked.

PMID- 19090775
TI  - Risk factors for early and late transmission of HIV via breast-feeding among
      infants born to HIV-infected women in a randomized clinical trial in Botswana.
AB  - Risk factors for mother-to-child transmission (MTCT) of human immunodeficiency
      virus (HIV) via breast-feeding were evaluated in a randomized trial. HIV-infected
      women and their infants received zidovudine as well as single-dose nevirapine or
      placebo. Infants were randomized to formula-feed (FF) or breast-feed (BF) in
      combination with zidovudine prophylaxis. Of 1116 at-risk infants, 6 (1.1%) in the
      FF group and 7 (1.3%) in the BF group were infected between birth and 1 month
      (P=.99). Maternal receipt of nevirapine did not predict early MTCT in the BF
      group (P=.45). Of 547 infants in the BF group at risk for late MTCT, 24 (4.4%)
      were infected. Maternal HIV-1 RNA levels in plasma (P<.001) and breast milk
      (P<.001) predicted late MTCT. These findings support the safety of 1 month of
      breast-feeding in combination with maternal and infant antiretroviral
      prophylaxis. Trial registration. ClinicalTrials.gov identifiers: NCT00197691 and
      NCT00197652.

PMID- 19090777
TI  - High deformability of Plasmodium vivax-infected red blood cells under
      microfluidic conditions.
AB  - Maturation of Plasmodium falciparum decreases the deformability of infected red
      blood cells (RBCs), increasing their clearance as they attempt to pass through
      endothelial slits of the splenic sinus. Previous studies of Plasmodium vivax
      infected RBCs led to opposite conclusions with respect to cellular deformability.
      To resolve this controversy, P. vivax-infected RBCs were passed through a 2
      microm microfluidic channel. In contrast to P. falciparum-infected RBCs, mature
      P. vivax-infected RBCs readily became deformed through 2-microm constrictions.
      After this extreme deformation, 67% of P. vivax-infected RBCs recovered a normal
      appearance; however, 15% of uninfected RBCs were destroyed. Results suggest
      mechanisms for both avoidance of splenic clearance and anemia in vivax malaria.

PMID- 19090778
TI  - Reactivation and mutation of newly discovered WU, KI, and Merkel cell carcinoma
      polyomaviruses in immunosuppressed individuals.
AB  - BACKGROUND: Infection with the human polyomaviruses BK (BKV) and JC (JCV) is
      almost ubiquitous, asymptomatic, and lifelong. However, reactivation during
      immunosuppression, associated with mutations in the transcriptional control
      region (TCR) that up-regulates viral replication, can cause life-threatening
      disease. In this study, we investigated whether the recently discovered WU and KI
      polyomaviruses (WUPyV and KIPyV) and Merkel cell polyomavirus (MCPyV) could, like
      BKV and JCV, persist, mutate, and reactivate in immunodeficient subjects.
      METHODS: Autopsy samples of lymphoid tissue from 42 AIDS-immunosuppressed
      subjects and 55 control samples were screened by polymerase chain reaction for
      all 5 polyomaviruses. TCR sequences from KIPyV and WUPyV recovered from both
      immunosuppressed and nonimmunosuppressed subjects were compared. RESULTS:
      Combined polyomavirus detection frequencies were much higher for the
      immunosuppressed group, compared with the nonimmunosuppressed group (35.7% vs.
      3.6%), with viral loads in lymphoid tissues ranging from < or = 8.4 x 10(5) to >
      1.5 x 10(5) viral genome copies per 10(6) cells. MCPyV was recovered from only 1
      HIV-negative study subject. TCR sequences from reactivated WUPyV and KIPyV
      variants showed a number of point mutations and insertions that were absent in
      viruses recovered from respiratory tract specimens obtained from
      nonimmunosuppressed subjects. CONCLUSIONS: KIPyV and WUPyV show reactivation
      frequencies comparable to those of BKV and JCV during immunosuppression. TCR
      changes that potentially lead to transcriptional dysregulation may have
      pathogenic consequences equivalent in severity to those observed for JCV and BKV.

PMID- 19090779
TI  - Discovery of multitarget inhibitors by combining molecular docking with common
      pharmacophore matching.
AB  - Multitarget drugs have been to be found effective in controlling complex
      diseases. However, how to design multitarget drugs presents a great challenge. We
      have developed a computer-assisted strategy to screen for multitarget inhibitors
      using a combination of molecular docking and common pharmacophore matching. This
      strategy was successfully applied to screen for dual-target inhibitors against
      both the human leukotriene A(4) hydrolase (LTA4H-h) and the human nonpancreatic
      secretory phospholipase A2 (hnps-PLA2). Three compounds screened from the
      chemical database MDL Available Chemical Directory were found to inhibit these
      two enzymes at the 10 microM level. Moreover, one synthetic compound matching the
      common pharmacophores inhibits LTA4H-h and hnps-PLA2 with IC(50) values of 35 nM
      and 7.3 microM, respectively. The common pharmacophore model can also be used to
      search small molecule databases or collections of existing inhibitors, as well as
      to guide combinatorial library design to search for ideal multitarget inhibitors.

PMID- 19090780
TI  - The protein tyrosine phosphatase non-receptor type 22 C1858T polymorphism is a
      joint susceptibility locus for immunthyroiditis and autoimmune diabetes.
AB  - BACKGROUND: The lymphoid tyrosine phosphatase (LYP) encoded by the protein
      tyrosine phosphatase non-receptor type 22 (PTPN22) gene is a strong inhibitor of
      T cells. The single nucleotide polymorphism (SNP) C1858T within the PTPN22 gene
      was recently associated with autoimmune thyroid disease (AITD) and type I
      diabetes (T1D). The purpose of this study was to examine the joint association of
      this polymorphism with the co-occurrence of AITD and T1D. METHODS: In this
      association study, 310 white subjects were genotyped for the C1858T polymorphism.
      The study population included 70 patients with both AITD and T1D (AITD+T1D), 70
      patients with AITD only, 70 patients with T1D only, and 100 healthy controls.
      Patients with both AITD and T1D, and controls were also typed for HLA-DRB1.
      PTPN22 C1858T genotyping was performed by minisequencing. For HLA-DRB1 typing,
      polymerase chain reaction (PCR) sequence-specific oligonucleotide probes were
      used. RESULTS: The PTPN22 1858 minor T-allele frequency was strongly increased in
      patients with AITD+T1D (23.6%) compared with controls (8.0%, pc<0.001), with
      patients with AITD only (8.6%, pc=0.006), or with T1D only (10.7%, pc=0.028). T
      allele carriers were also more frequently present in the group with AITD+T1D
      versus controls (41.4% vs. 14.0%, OR=4.35, 95% CI=2.08-9.09), AITD (17.1%,
      OR=3.42, 95% CI=1.56-7.48), and T1D (21.4%, OR=2.59, 95% CI=1.23-5.45).
      Especially in subjects with Hashimoto's thyroiditis (HT)+T1D, T-allele carriers
      were mostly frequent (50% vs. 14%, OR=6.14, 95% CI=2.62-14.38, pc<0.001).
      Considering all included patients with AITD, T-allele carriers were 29.3% vs.
      14.0% in controls (p=0.008, OR=2.54, 95% CI=1.30-4.98). Patients carrying the
      PTPN22 1858 T allele had a twofold increased frequency of the HLA-DRB1*03 allele
      (64.7% vs. 37.3%, pc=0.034). CONCLUSION: The PTPN22 gene is a joint
      susceptibility locus for AITD (especially HT) and T1D.

PMID- 19090781
TI  - Systematic research of peptide spacers controlling drug release from
      macromolecular prodrug system, carboxymethyldextran polyalcohol-peptide-drug
      conjugates.
AB  - The primary purpose of this study was to comprehensively delineate specificity of
      the peptide spacer sequence to tumor-expressed proteases for the design of
      macromolecular carrier-peptide spacer-drug conjugate system. 225 conjugates of
      carboxymethyldextran polyalcohol (CM-Dex-PA) as water-soluble carrier and a
      dansyl derivative (N-(4-aminobutyl)-5-(dimethylamino)-1-naphthalenesulfonamide,
      DNS) as the model drug linked with different tetrapeptide spacers (Gly-Gly-P(2)
      P(1), P(2), P(1): Ala, Asn, Gly, Cit, Gln, Ile, Leu, Met, Phe, Pro, Ser, Thr,
      Trp, Tyr, and Val) were combinatorially synthesized. First, the drug release
      assay of all of the fluorogenic model conjugates was performed in murine Meth A
      solid tumor homogenates. The drug release rate was higher with conjugates having
      hydrophobic amino acids at P(2). It was also found that conjugates with Asn
      release the drug rapidly and, in contrast, those with Pro does not. Second, we
      selected three peptide spacers (Gly-Gly-Phe-Gly, Gly-Gly-Ile-Gly, Gly-Gly-Pro
      Leu), which release only DNS at different rates, and applied them to doxorubicin
      (DXR) conjugates. These three DXR conjugates were used for investigating
      relationships with drug release, pharmacokinetics, and antitumor activity against
      Meth A bearing mice of these conjugates. The release of DXR from the conjugates
      corresponded well with that of DNS conjugates in tumor homogenates. CM-Dex-PA-Gly
      Gly-Phe-Gly-DXR and CM-Dex-PA-Gly-Gly-Ile-Gly-DXR indicated strong antitumor
      activity, with the comparable pharmacokinetic profile of released DXR in tumor.
      Taken with the fact that the drug release rate in tumor homogenates was
      approximately 10-fold different between these two DXR conjugates, it is likely
      that cellular uptake of the conjugate would be rate-limiting, rather than the
      drug release process under the in vivo situation. However, much weaker antitumor
      activity was observed with CM-Dex-PA-Gly-Gly-Pro-Leu-DXR, of which the drug
      release was extremely slow.

PMID- 19090782
TI  - Fumaric acid monoethyl ester-functionalized poly(D,L-lactide)/N-vinyl-2
      pyrrolidone resins for the preparation of tissue engineering scaffolds by
      stereolithography.
AB  - Polymer networks were prepared by photocross-linking fumaric acid monoethyl ester
      (FAME) functionalized, three-armed poly(D,L-lactide) oligomers using N-vinyl-2
      pyrrolidone (NVP) as diluent and comonomer. The use of NVP together with FAME
      functionalized oligomers resulted in copolymerization at high rates, and networks
      with gel contents in excess of 90% were obtained. The hydrophilicity of the
      poly(D,L-lactide) networks increases with increasing amounts of NVP, networks
      containing 50 wt % of NVP absorbed 40% of water. As the amount of NVP was
      increased from 30 to 50 wt %, the Young's modulus after equilibration in water
      decreased from 0.8 to 0.2 GPa, as opposed to an increase from 1.5 to 2.1 GPa in
      the dry state. Mouse preosteoblasts readily adhered and spread onto all prepared
      networks. Using stereolithography, porous structures with a well-defined gyroid
      architecture were prepared from these novel materials. This allows the
      preparation of tissue engineering scaffolds with optimized pore architecture and
      tunable material properties.

PMID- 19090783
TI  - Suppression of protein adsorption on a charged phospholipid polymer interface.
AB  - High capability of a charged interface to suppress adsorption of both anionic and
      cationic proteins was reported. The interface was covalently constructed on
      quartz by modifying with an anionic phospholipid copolymer, poly(2
      methacryloyloxyethyl phosphorylcholine (MPC)-co-n-butyl methacrylate (BMA)-co
      potassium 3-methacryloyloxypropyl sulfonate (PMPS)-co-3-methacryloxypropyl
      trimethoxysilane (MPTMSi)) (PMBSSi). The PMBSSi interfaces were very hydrophilic
      and homogeneous and could function effectively for a long time even under long
      term fluidic working conditions. The PMBSSi density on the interface, which was
      controllable by adjusting the PMBSSi concentration of the modification solution,
      affected the surface properties, including the surface contact angle, the surface
      roughness, and the surface zeta-potential. When a PMBSSi modification was
      applied, the adsorption of various proteins (isoelectric point varying from 1.0
      to 11.0) on quartz was reduced to at least 87% in amount, despite the various
      electrical natures these proteins have. The protein adsorption behavior on the
      PMBSSi interface depended more on the PMBSSi density than on the surface charge.
      The PMBSSi modification had a stable impact on the surface, not only at the
      physiologic ionic strength, but also over a range of the ionic strength,
      suggesting that electrostatic interactions do not dominate the behavior of
      protein adsorption to the PMBSSi surface.

PMID- 19090784
TI  - Role of the N-terminal tail of metal-transporting P(1B)-type ATPases from genome
      wide analysis and molecular dynamics simulations.
AB  - Copper is an essential trace metal but can be potentially toxic in vivo.
      Consequently, its intracellular concentration and distribution is tightly
      controlled. A widespread system involved in maintaining copper homeostasis in a
      variety of prokaryotic and eukaryotic organisms involves a P-type ATPase, which
      pumps the metal ion from the cytosol at the expense of ATP hydrolysis. Copper
      transporting ATPases of this kind are often associated with a small soluble metal
      transporter (metallochaperone). In this work, we investigated the occurrence and
      properties of the ATPases and, partly, of their partner metallochaperones. We
      found that the latter proteins are typically encoded in organisms containing also
      ATPases of the subtypes 1B-1 or 1B-2. These subtypes have a characteristically
      extended N-terminal cytoplasmic tail that contains multiple metal-binding domains
      (MBDs), which can receive the metal ion from the metallochaperone. We observed a
      significant variability in the number and spacing in sequence of the MBDs. On the
      basis of molecular dynamics simulations, we proposed that the MBDs could be quite
      free to reorient with respect to one another. The relative conformational freedom
      increased rapidly with the length of the linker between the MBDs. Also based on
      available experimental studies, these data suggested that the reciprocal mobility
      of the MBDs is instrumental to permit the tuning of the selectivity and/or
      affinity of the ATPase for the substrate as well as to modulate the enzymatic
      activity of the system. We additionally detected a small but significant number
      of instances in which a metallochaperone is likely to interact directly with the
      transmembrane domain of P-type ATPases lacking cytoplasmic MBDs.

PMID- 19090785
TI  - Reaction-MQL: line notation for functional transformation.
AB  - Representation of chemical reactions is pivotal for different purposes in
      cheminformatics. We present an extension of the molecular query language (MQL),
      which combines readable style with meaningful rules for string representation of
      reactions and unambiguous product formation. The concept of functional groups is
      used to describe the transformations. Functional groups are defined in terms of
      substructure queries and are processed by graph transformations. Molecular educt
      graphs are transformed by application of beginning-, end-, and reaction-matrices
      to obtain the product graph without consideration of stereochemistry. Both
      directions of a transformation are possible. We implemented the concept of
      Reaction-MQL in Java employing the Chemistry Development Kit.

PMID- 19090786
TI  - NAADP-mediated channel 'chatter' in neurons of the rat medulla oblongata.
AB  - NAADP (nicotinic acid-adenine dinucleotide phosphate) is a potent Ca(2+)
      mobilizing messenger that stimulates Ca(2+) release in a variety of cells. NAADP
      sensitive Ca(2+) channels are thought to reside on acidic Ca(2+) stores and to be
      functionally coupled to IP(3) (inositol 1,4,5-trisphosphate) and/or ryanodine
      receptors located on the endoplasmic reticulum. Whether NAADP-sensitive Ca(2+)
      channels 'chatter' to other channels, however, is not clear. In the present
      study, we have used a cell-permeant NAADP analogue to probe NAADP-mediated
      responses in rat medulla oblongata neurons. NAADP-AM (NAADP-acetoxymethyl ester)
      evoked global cytosolic Ca(2+) signals in isolated neurons that were reduced in
      amplitude by removal of external Ca(2+), abolished by disruption of acidic
      compartments and substantially inhibited by blockade of ryanodine receptors. In
      rat medullary slices, NAADP-AM depolarized neurons from the nucleus ambiguus in
      the presence of intracellular EGTA, but not of the faster Ca(2+) chelator BAPTA
      [1,2-bis-(o-aminophenoxy)ethane-N,N,N',N'-tetra-acetic acid]. Depolarization was
      also dependent upon extracellular Ca(2+), acidic stores and ryanodine receptors.
      In voltage-clamp mode, NAADP-AM induced an inward current with a reversal
      potential of approx. 0 mV. The results of the present study reveal the presence
      of acidic NAADP-sensitive Ca(2+) stores in medulla neurons, the mobilization of
      which results not only in global Ca(2+) signals but also in local signals that
      activate non-selective cation channels on the cell surface resulting in
      depolarization. Thus NAADP is capable of co-ordinating channels both within the
      cell interior and at the cell membrane representing a novel mechanism for
      excitation of central neurons.

PMID- 19090787
TI  - Variant c-type cytochromes as probes of the substrate specificity of the E. coli
      cytochrome c maturation (Ccm) apparatus.
AB  - c-type cytochromes are normally characterized by covalent attachment of the iron
      cofactor haem to protein through two thioether bonds between the vinyl groups of
      the haem and the thiol groups of a CXXCH (Cys-Xaa-Xaa-Cys-His) motif. In cells,
      the haem attachment is an enzyme-catalysed post-translational modification. We
      have previously shown that co-expression of a variant of Escherichia coli
      cytochrome b(562) containing a CXXCH haem-binding motif with the E. coli Ccm
      (cytochrome c maturation) proteins resulted in homogeneous maturation of a
      correctly formed c-type cytochrome. In contrast, in the absence of the Ccm
      apparatus, the product holocytochrome was heterogeneous, the main species having
      haem inverted and attached through only one thioether bond. In the present study
      we use further variants of cytochrome b(562) to investigate the substrate
      specificity of the E. coli Ccm apparatus. The system can mature c-type
      cytochromes with CCXXCH, CCXCH, CXCCH and CXXCHC motifs, even though these are
      not found naturally and the extra cysteine residue might, in principle, disrupt
      the biogenesis proteins which must interact intricately with disulfide-bond
      oxidizing and reducing proteins in the E. coli periplasm. The Ccm proteins can
      also attach haem to motifs of the type CX(n)CH where n ranges from 2 to 6. For
      n=3 and 4, the haem attachment was correct and homogeneous, but for higher values
      of n the holocytochromes displayed oxidative addition of sulfur and/or oxygen
      atoms associated with the covalent haem-attachment process. The implications of
      our observations for the haem-attachment reaction, for genome analyses and for
      the substrate specificity of the Ccm system, are discussed.

PMID- 19090788
TI  - Effect of intensive lipid-lowering therapy on telomere erosion in endothelial
      progenitor cells obtained from patients with coronary artery disease.
AB  - Telomere erosion of EPCs (endothelial progenitor cells) may be a key factor in
      endothelial cell senescence and is highly dependent on cellular oxidative damage.
      The aim of the present study was to investigate whether LLT (lipid-lowering
      therapy) with statins could attenuate EPC telomere erosion in patients with CAD
      (coronary artery disease). The study included 100 patients with stable CAD and 25
      subjects without CAD as controls. CAD patients were randomized to 12 months of
      intensive LLT with atorvastatin or moderate LLT with pravastatin. EPCs were
      obtained from peripheral blood at baseline and after 12 months of statin therapy.
      Telomere length in EPCs was measured by FISH (fluorescence in situ hybridization)
      and oxidative DNA damage by flow cytometry of oxidized DNA bases. EPC telomere
      length was shorter in the CAD group than in the controls, and oxidative DNA
      damage to EPCs was higher in the CAD group compared with controls. After 12
      months of therapy, changes in lipid profiles were greater in the intensive LLT
      group than in the moderate LLT group. Intensive LLT markedly increased EPC number
      and decreased oxidative DNA damage in EPCs (both P<0.05), with no change in
      telomere length. In contrast, moderate LLT did not change EPC counts or oxidative
      DNA damage, but showed telomere shortening (P<0.05). There was a weak negative
      correlation between changes in EPC number and LDL (low-density lipoprotein)
      cholesterol levels after intensive LLT, whereas there was no correlation between
      them after moderate LLT. With in vitro culturing of EPCs subjected to oxidative
      stress, atorvastatin led to the prevention of EPC telomere shortening compared
      with pravastatin. In conclusion, the present study has demonstrated that
      intensive LLT may prevent EPC telomere erosion in patients with CAD, possibly
      contributing to the beneficial effects of intensive LLT in this disorder.

PMID- 19090789
TI  - Palmitoylation of the TRAIL receptor DR4 confers an efficient TRAIL-induced cell
      death signalling.
AB  - S-palmitoylation is a lipid modification that regulates membrane-protein
      association and influences protein trafficking, stability or aggregation, thus
      playing an important role in protein signalling. We previously demonstrated that
      the palmitoylation of Fas, one of the DD (death domain)-containing members of the
      TNFR [TNF (tumour necrosis factor) receptor] superfamily, is essential for the
      redistribution of this receptor into lipid rafts, an obligatory step for the
      death signal transmission. Here we investigate the requirement of protein
      palmitoylation in the activities of other DD-containing death receptors. We show
      that DR4 is palmitoylated, whereas DR5 and TNFR1 are not. Furthermore, DR4
      palmitoylation is required for its raft localization and its ability to
      oligomerize, two essential features in TRAIL (TNF-related apoptosis-inducing
      ligand)-induced death signal transmission.

PMID- 19090791
TI  - Impact factors and the Journal of Travel Medicine.

PMID- 19090790
TI  - A region N-terminal to the tandem SH3 domain of p47phox plays a crucial role in
      the activation of the phagocyte NADPH oxidase.
AB  - The superoxide-producing NADPH oxidase in phagocytes is crucial for host defence;
      its catalytic core is the membrane-integrated protein gp91phox [also known as
      Nox2 (NADPH oxidase 2)], which forms a stable heterodimer with p22phox.
      Activation of the oxidase requires membrane translocation of the three cytosolic
      proteins p47phox, p67phox and the small GTPase Rac. At the membrane, these
      proteins assemble with the gp91phox-p22phox heterodimer and induce a
      conformational change of gp91phox, leading to superoxide production. p47phox
      translocates to membranes using its two tandemly arranged SH3 domains, which
      directly interact with p22phox, whereas p67phox is recruited in a p47phox
      dependent manner. In the present study, we show that a short region N-terminal to
      the bis-SH3 domain is required for activation of the phagocyte NADPH oxidase.
      Alanine substitution for Ile152 in this region, a residue that is completely
      conserved during evolution, results in a loss of the ability to activate the
      oxidase; and the replacement of Thr153 also prevents oxidase activation, but to a
      lesser extent. In addition, the corresponding isoleucine residue (Ile155) of the
      p47phox homologue Noxo1 (Nox organizer 1) participates in the activation of non
      phagocytic oxidases, such as Nox1 and Nox3. The I152A substitution in p47phox,
      however, does not affect its interaction with p22phox or with p67phox. Consistent
      with this, a mutant p47phox (I152A), as well as the wild-type protein, is
      targeted upon cell stimulation to membranes, and membrane recruitment of p67phox
      and Rac normally occurs in p47phox (I152A)-expressing cells. Thus the Ile152
      containing region of p47phox plays a crucial role in oxidase activation, probably
      by functioning at a process after oxidase assembly.

PMID- 19090792
TI  - Clinic in the air? A retrospective study of medical emergency calls from a major
      international airline.
AB  - BACKGROUND: There is a high likelihood of a medical professional being onboard
      the aircraft at the time of emergency. Therefore, a health-care professional
      should be familiar with in-flight medical events and how to deal with them.
      METHODS: I present a 12-month retrospective study of medical distress calls from
      a major Asian international airline for which International SOS provided in
      flight telemedical assistance. All the calls from the airplane to our center were
      analyzed from January 1, 2006, to January 1, 2007. The number of recommended
      diversions, availability of a medical professional, the range of medical
      problems, and used medications were considered. RESULTS: Overall, there were 191
      in-flight air-to-ground consultations. Twenty-three (12.04%) calls were made for
      pediatric problems, with the youngest patient being 9 months old.
      Gastrointestinal complaints and simple faints comprised 50.2% of all calls. Most
      of the in-flight problems were successfully treated symptomatically with the
      initial recommendation to lie the patient down and administer oxygen.
      Metoclopramide, stemetil, loperamide, and buscopan were the most often
      administered drugs. A doctor was onboard in 45.5% of all calls. A recommendation
      to divert the aircraft was made in six (3.1%) cases. CONCLUSIONS: Although
      developments in telemedical assistance and the content of a medical kit make the
      management of potential in-flight medical emergency much easier, they will never
      turn a commercial aircraft into a flying clinic. Preflight check-in screening by
      airlines and encouraging future air travelers with health concerns to seek
      medical help before flying should be recommended.

PMID- 19090793
TI  - Monitoring injury in the New Zealand adventure tourism sector: an operator
      survey.
AB  - BACKGROUND: Client safety is a major risk management concern for the commercial
      adventure tourism sector in New Zealand. This study built on previous exploratory
      analyses of New Zealand adventure tourism safety, including industry surveys
      conducted by these authors in 1999 and 2003. The aims of the study were to
      provide a continuation of injury monitoring across the sector through data
      collected from self-reported injury incidence by industry operators and to
      compare findings with those from other primary and secondary research studies
      conducted by the authors. METHODS: A postal questionnaire was used to survey all
      identifiable New Zealand adventure tourism operators during 2006. The
      questionnaire asked respondents about their recorded client injury experience,
      perceptions of client injury risk factors, and safety management practices.
      RESULTS: Some 21 adventure tourism activities were represented among the
      responding sample (n = 127), with most operations being very small in terms of
      staff numbers, although responding operators catered to nearly 1 million clients
      in total annually. Highest ranked risk factors for client injury included clients
      not following instructions; level of client skill, ability, and fitness; and
      changeable/unpredictable weather conditions. Highest client injury was reported
      for horse riding, ecotourism, and white water rafting sectors, although serious
      underreporting of minor injuries was evidenced across the sector. Slips, trips,
      and falls were the most frequently reported injury mechanism, while safety
      management measures were inconsistently applied across the sector. CONCLUSIONS:
      The industry should address reporting culture issues and safety management
      practices generally. Specifically, the industry should consider risk management
      that focuses on minor (eg, falls) as well as catastrophic events.

PMID- 19090794
TI  - Recreational travel fatalities in US national parks.
AB  - BACKGROUND: Injuries are a public health problem affecting traveling populations
      such as tourists visiting National Parks. This study investigates the
      distribution of visitor fatalities in US National Park Service (NPS) units and
      identifies the predeath activities and contributing factors associated with them.
      METHODS: A retrospective study was conducted of visitor fatalities from all NPS
      units during 2003 and 2004. RESULTS: There were 356 reported fatalities during
      2003 and 2004. Fatalities were most common during the summer months and on
      weekends. Males accounted for 75% of the reported fatalities, and visitors aged
      20 to 29 and 50 to 59 years accounted for 51% of all deaths. Only 99 of 388 (26%)
      NPS units reported at least 1 fatality, and only 10 units reported 10 or more
      fatalities. However, these 10 units were responsible for 36% of all fatalities.
      Lake Mead National Recreation Area, Blue Ridge Parkway, Grand Canyon National
      Park, Great Smoky Mountains National Park, and Yosemite National Park reported
      the highest number of fatalities. Domestic visitors accounted for 73% of the
      fatalities, and European visitors accounted for 13%. Transportation and water
      based activities recorded the highest number of fatalities. Motor vehicle crashes
      accounted for 20% of fatalities and was followed by suicide (17%), swimming
      (11%), hiking (10%), plane crashes (9%), climbing (6%), and boating (5%)
      incidents. CONCLUSIONS: Fatalities in NPS units are not widespread and are
      related to more common events such as motor vehicle crashes, suicide, swimming,
      and hiking rather than exotic causes such as bears or other wildlife. It is
      recommended that preventive techniques first be developed in the 10 NPS units
      responsible for 36% of the total NPS-wide fatalities.

PMID- 19090795
TI  - Enterotoxigenic Escherichia coli and diffusely adherent E. coli as likely causes
      of a proportion of pathogen-negative travelers' diarrhea--a PCR-based study.
AB  - BACKGROUND: Enteropathogens cannot be identified in 40% to 50% of subjects with
      travelers' diarrhea (TD). METHODS: We used polymerase chain reaction (PCR)
      methods to look for the presence of two bacterial causes of diarrhea in a large
      group of international travelers after failing to detect a pathogen by
      conventional tests. DNA was isolated from the diarrheal stool and subjected to
      PCR from 162 subjects from whom we earlier failed to identify a pathogen in a
      previous study and included 54 from Antigua, Guatemala, 39 from Guadalajara,
      Mexico, 29 from Kolkata, India, and 40 from Goa, India. Gene products for
      enterotoxigenic Escherichia coli (ETEC)--LT (heat-labile enterotoxin) and ST
      (heat-stable enterotoxin)--and diffusely adherent E. coli (DAEC), afa/dr (Afa
      fimbrial and Dr nonfimbrial family of adhesins), were used. RESULTS: At least one
      gene product was identified in diarrhea stool samples of 47 of 162 (29%)
      subjects. ETEC virulence genes (LT, ST) were found in 34 (21%) samples studied,
      with rates of occurrence ranging from 8% in Goa to 39% for the samples from
      Guatemala (p = 0.0006). A large number of ST-only strains explained the high ETEC
      rate in Guatemala. DAEC afa/dr family of adhesions was identified in between 8
      and 14% of the samples. CONCLUSIONS: ETEC and DAEC were implicated in nearly one
      third of the subjects initially diagnosed as pathogen negative. Direct PCR
      results from stools are consistent with the previous assumption that most
      undiagnosed TD is bacterial in nature and also highlights the potential value
      that PCR can add to studies designed to evaluate treatment and preventive
      interventions for TD, including vaccines.

PMID- 19090796
TI  - Trends of norfloxacin and erythromycin resistance of Campylobacter
      jejuni/Campylobacter coli isolates recovered from international travelers, 1994
      to 2006.
AB  - BACKGROUND: Campylobacter sp. is a major cause of bacterial enterocolitis and
      travelers' diarrhea. Empiric treatment regimens include fluoroquinolones and
      macrolides. METHODS: Over the period 1994 to 2006, 724 Campylobacter
      jejuni/Campylobacter coli isolates recovered from international travelers at the
      outpatient clinic of the Institute of Tropical Medicine, Antwerp, Belgium, were
      reviewed for their susceptibility to norfloxacin and erythromycin. RESULTS:
      Norfloxacin resistance increased significantly over time in isolates from
      travelers returning from Asia, Africa, and Latin America. For the years 2001 to
      2006, norfloxacin resistance rates were 67 (70.5%) of 95 for Asia, 20 (60.6%) of
      33 for Latin America, and 36 (30.6%) of 114 for Africa. The sharpest increase was
      noted for India, with no resistance in 1994, but 41 (78.8%) of 52 resistant
      isolates found during 2001 to 2006. Erythromycin resistance was demonstrated in
      20 (2.7%) isolates, with a mean annual resistance of 3.1% +/- 2.8%; resistance
      increased over time, with up to 3(7.5%) of 40 and 3 (8.6%) of 35 resistant
      isolates in 2004 and 2006, respectively (p < 0.05); there was no apparent
      geographic association. Combined resistance to norfloxacin and erythromycin was
      observed in five isolates. CONCLUSIONS: The high resistance rates to
      fluoroquinolones warrant reconsideration of their use as drugs of choice in
      patients with severe gastroenteritis when Campylobacter is the presumed cause.
      Continued monitoring of the incidence and the spread of resistant Campylobacter
      isolates is warranted.

PMID- 19090797
TI  - Validity of malaria diagnosis in nonimmune travelers in endemic areas.
AB  - BACKGROUND: Malaria has to be considered in all febrile travelers during or after
      a stay in endemic areas. However, malaria diagnosis in endemic countries may be
      inaccurate due to limited capacity and lack of resources of local health
      services. To assess the validity of malaria diagnosis in travelers in endemic
      areas, we investigated the retrospective confirmation of malaria by detection of
      specific antibodies. METHODS: Sera of 105 nonimmune travelers who presented
      between 2003 and 2005 with a history of diagnosis and treatment of malaria during
      a stay in malaria-endemic countries within the previous 6 months were analyzed
      for antibodies against Plasmodium falciparum and Plasmodium vivax blood forms by
      an indirect immunofluorescence test. About 241 follow-up sera from 176 nonimmune
      patients with microscopically confirmed malaria served as a control group.
      RESULTS: Antibodies against plasmodia were detectable within 180 days after
      reported date of diagnosis and treatment in 16 of 105 travelers (15.2%) only. In
      the control group, 71.6% of analyzed sera (151 of 211) showed positive results
      within this interval. Within 8 to 60 days after diagnosis of malaria, the
      seropositivity rates were 17.9% for travelers (n = 56) and 92.4% for controls (n
      = 92). CONCLUSIONS: Although the sensitivity of malaria serology for
      retrospective confirmation of malaria is limited, the results of this analysis
      strongly suggest that the majority of travelers with a recent history of malaria
      diagnosed and treated in endemic countries did not have malaria and that
      diagnosis of malaria during travel in endemic areas is frequently incorrect.

PMID- 19090798
TI  - Trends in imported malaria to Basel, Switzerland.
AB  - BACKGROUND: Due to persistent international travel and immigration trends,
      imported malaria remains to be of clinical and public health importance in
      nonendemic countries. The aim of this study was to investigate trends in imported
      malaria over a period of more than three decades. METHODS: We assessed travel
      history, demographic characteristics, and clinical course with special regard to
      malaria diagnosis and intensive care unit (ICU) admission of patients diagnosed
      with malaria. The sample comprised 109 patients with the diagnosis of malaria
      according to the International Statistical Classification of Diseases and Related
      Health Problems (ICD)-coding system (versions 9 and 10) at the University
      Hospital and at a teaching hospital in Basel between January 1994 and June 2004.
      Changes in clinical management and outcomes were compared with previous studies
      at the same institutions dating back to the 1970s. RESULTS: The most common
      reason for travel was to visit friends and relatives in the country of origin
      (37%), and most infections were acquired in Africa (82%), with Plasmodium
      falciparum malaria the most frequently found parasite (84%). The mean time
      between first symptoms and the diagnosis of malaria was 4 days (range 0.5-31 d).
      Delay in diagnosis occurred in 14% of cases, and 37% of hospitalized patients
      were referred to the ICU. In 22% of referred cases, high parasitemia (>2%)
      according to internal criteria was a reason for referral. The course of disease
      remained mild in the great majority (90%) of patients, and none of the patients
      died. CONCLUSIONS: Prompt and specific diagnosis of malaria could be improved.
      Malaria-associated mortality was reduced over time. As ICU referral showed to be
      inappropriately high in relation to a moderate clinical course of several
      admitted patients, criteria for ICU admission should be reevaluated. The trend
      toward malaria in patients originating from endemic areas suggests that
      preventive travel advice should specifically address these patients.

PMID- 19090799
TI  - Pretravel consultation: rapid dipstick test as a decision guidance for the
      application of tetanus booster vaccinations.
AB  - BACKGROUND: When deciding whether to administer a tetanus vaccination--for
      international travel or injury--a subject's vaccination certificate should be
      investigated. As many people lack valid vaccination cards and are unable to
      recall their vaccination history, the Tetanos Quick Stick (TQS) test rapidly
      detects protective tetanus immunoglobulin IgG antibodies in whole blood, serum,
      or plasma. This immunochromatographic dipstick test yields a positive or negative
      result. METHODS: Our study evaluates the effectiveness of the TQS test by
      comparing the binary TQS test results of 100 sera with the tetanus antibody
      levels as measured by the standardized enzyme-linked immunosorbent assay (ELISA)
      method. We used the TQS test to determine whether a person needed a tetanus
      booster vaccination. If the test showed a clearly visible line that was similar
      to the control line, the result was determined to be positive. RESULTS: All
      positive TQS test results had a concentration of IgG antibodies above 0.5 IU/mL
      as measured by ELISA, indicating that no booster vaccination was required.
      Similarly, in all cases with an antibody level below 0.1 IU/mL, where a
      vaccination would have been recommended based on the ELISA test result, the TQS
      test yielded a negative result. The positive predictive value and the specificity
      for the dipstick test were therefore 100%. CONCLUSIONS: The TQS test is a
      reliable, fast, and cost-effective means of identifying subjects with a
      preexisiting level of tetanus IgG antibodies above approximately 0.5 IU/mL. This
      can help to avoid unnecessary tetanus vaccinations in travel clinics, emergency
      departments, and practices of family doctors.

PMID- 19090801
TI  - Travel-acquired leptospirosis.

PMID- 19090800
TI  - Should health-care providers in the United States have access to influenza
      vaccines formulated for the southern hemisphere?
AB  - BACKGROUND: Influenza is the most common vaccine-preventable disease in
      travelers. It circulates year-round in the tropics, November to March in the
      northern hemisphere (NH), and April to October in the southern hemisphere (SH).
      In 2005, approximately 8.5 million US adults aged 18 years and older traveled to
      the Caribbean. A similar number traveled to the tropics and the SH. SH
      formulation of influenza vaccine is not available in the United States. We
      surveyed International Society of Travel Medicine (ISTM) members to ask if they
      would use SH influenza vaccine if available. METHODS: We electronically mailed a
      survey in December 2006 to 1,251 ISTM members in the United States. We asked if
      respondents would use SH vaccine for patients traveling to the SH or tropics, how
      many such patients per week they see, and their practice location. RESULTS: We
      received 157 responses for a response rate of 12.5%. Of these, 129 (82%) stated
      that they would be interested in having SH influenza vaccine available. Of those
      indicating interest, 73 (60%) reported seeing >10 patients traveling to the SH or
      tropics each week. Respondents reported practice settings in 34 states and the
      District of Columbia. Respondents requested more information about the likely
      cost of SH influenza vaccine, ordering conditions, vaccine use guidelines,
      comparability with NH vaccine, and approval of SH vaccine by the Food and Drug
      Administration. CONCLUSIONS: Many travelers to the SH are at risk for influenza
      infection. Although only a limited number of ISTM members responded, respondents
      indicated considerable interest in availability of SH influenza vaccine for their
      patients. More data from travel medicine and other practitioners are needed on
      this topic. Inquiries are being made of influenza vaccine manufacturers about
      licensing SH influenza vaccines in the United States. Adding SH influenza vaccine
      to the vaccines available to NH clinicians could help mitigate the morbidity of
      influenza in travelers.

PMID- 19090802
TI  - Frequent international travel by men who have sex with men recently diagnosed
      with HIV-1: potential for transmission of primary HIV-1 drug resistance.
AB  - We assessed the potential for international transmission of primary drug
      resistance among men who have sex with men newly diagnosed with human
      immunodeficiency virus (HIV) (n = 64) during the period in which they were
      unaware of their infection. During their exposure period, 55% of participants
      lived or traveled outside of the United States, and 59% had foreign-born sexual
      partners. Eighteen participants (28%) were classified as recently infected with
      HIV. Primary HIV-1 drug resistance was detected in eight participants (13%), four
      of whom were recently infected. Given the high frequency of international travel
      and prevalence of primary HIV-1 drug resistance among study participants,
      prevention strategies should incorporate specific counseling on risk of cross
      border transmission.

PMID- 19090803
TI  - Health problems in returning travelers consulting general practitioners.
AB  - Over a 2-month period, 43 of 143 participating general practitioners included 97
      patients with 113 health impairments, mainly gastrointestinal problems (35%),
      respiratory tract infections (30%), and skin diseases (11%). Systemic febrile
      illness or imported tropical disease accounted for less than 4% of cases.

PMID- 19090804
TI  - Salmonella panama and acute respiratory distress syndrome in a traveler taking a
      proton pump inhibitor.
AB  - Acute respiratory distress syndrome (ARDS) is a rare complication of enteric
      fever. We present an immunocompetent traveler to Nicaragua who developed enteric
      fever from Salmonella panama complicated by ARDS. Unlike her fellow travelers who
      also became ill, she was taking a proton pump inhibitor, which may have
      contributed to the disease severity.

PMID- 19090805
TI  - Pruritic dermatitis on an oil tanker after a visit to French Guyana.
AB  - A 40-year-old seaman presented to our emergency department with a severe pruritic
      skin reaction on his limbs and neck after visiting French Guyana on an oil
      tanker. Twenty crewmembers had had the same complaints. The harbor in French
      Guyana had been devastated by an invasion of Hylesia metabus, a moth that can
      cause a serious dermatitis due to contact with the hairs (setae) of the female
      moth. Complaints due to contact with caterpillars, butterflies, or moths is
      called lepidopterism. The complaints are self-limiting, and treatment is
      symptomatic. Due to the increasing amount of travelers and the normally harmless
      character of butterflies and moths, we would like to heighten the awareness of
      this relatively unknown condition.

PMID- 19090806
TI  - Successful diagnosis and treatment 50 years after exposure: is mucocutaneous
      leishmaniasis still a neglected differential diagnosis?
AB  - We present a case of a long-term history of imported mucocutaneous leishmaniasis,
      illustrating the importance of this differential diagnosis even decades after
      exposure. Diagnostic pitfalls and the role of primary subspecies differentiation
      are demonstrated. Chemotherapy avoiding antimonials was successful and remarkably
      well tolerated by an elderly patient.

PMID- 19090807
TI  - Determinants of malaria prophylaxis among german travelers to Kenya, Senegal, and
      Thailand.

PMID- 19090808
TI  - Crystal structure of Methanococcus jannaschii TATA box-binding protein.
AB  - As the archaeal transcription system consists of a eukaryotic-type transcription
      apparatus and bacterial-type regulatory transcription factors, analyses of the
      molecular interface between the transcription apparatus and regulatory
      transcription factors are critical to reveal the evolutionary change of the
      transcription system. TATA box-binding protein (TBP), the central components of
      the transcription apparatus are classified into three groups: eukaryotic,
      archaeal-I and archaeal-II TBPs. Thus, comparative functional analysis of these
      three groups of TBP is important for the study of the evolution of the
      transcription system. Here, we present the first crystal structure of an archaeal
      II TBP from Methanococcus jannaschii. The highly conserved and group-specific
      conserved surfaces of TBP bind to DNA and TFIIB/TFB, respectively. The
      phylogenetic trees of TBP and TFIIB/TFB revealed that they evolved in a coupled
      manner. The diversified surface of TBP is negatively charged in the archaeal-II
      TBP, which is completely different from the case of eukaryotic and archaeal-I
      TBPs, which are positively charged and biphasic, respectively. This difference is
      responsible for the diversification of the regulatory functions of TBP during
      evolution.

PMID- 19090809
TI  - Caenorhabditis elegans Rab escort protein (REP-1) differently regulates each Rab
      protein function and localization in a tissue-dependent manner.
AB  - Rab proteins play a critical role in intracellular vesicle trafficking and
      require post-translational modification by adding lipids at the C-terminus for
      proper functions. This modification is preceded by the formation of a trimeric
      protein complex with the Rab escort protein (REP) and the Rab
      geranylgeranyltransferase (RabGGTase). However, the genetic hierarchy among these
      proteins and the tissue-specificity of each protein function are not yet clearly
      understood. Here we identified the Caenorhabditis elegans rep-1 gene and found
      that a rep-1 mutant showed a mild defect in synaptic transmission and defecation
      behaviors. Genetic analyses using the exocytic Rab mutants rab-3 or rab-27
      suggested that rep-1 functions only in the RAB-27 pathway, and not in the RAB-3
      pathway, for synaptic transmission at neuromuscular junctions. However, the
      disruption of REP-1 did not cause defecation defects compared to severe defects
      in either RAB-27 or RabGGTase disruption, suggesting that REP-1 is not essential
      for RAB-27 signaling in defection. Some Rab proteins did not physically interact
      with REP-1, and localization of these Rab proteins was not severely affected by
      REP-1 disruption. These findings suggest that REP-1 functions are required in
      specific Rab pathways and in specific tissues, and that some Rab proteins are
      functionally prenylated without REP-1.

PMID- 19090811
TI  - N-acetyltransferase ARD1-NAT1 regulates neuronal dendritic development.
AB  - ARD1 and NAT1 constitute an N-acetyltransferase complex where ARD1 holds the
      enzymatic activity of the complex. The ARD1-NAT1 complex mediates N-terminal
      acetylation of nascent polypeptides that emerge from ribosomes after translation.
      ARD1 may also acetylate the internal lysine residues of proteins. Although ARD1
      and NAT1 have been found in the brain, the physiological role and substrates of
      the ARD1-NAT1 complex in neurons remain unclear. Here we investigated role of N
      acetyltransferase activity in the process of neuronal development. Expression of
      ARD1 and NAT1 increased during dendritic development, and both proteins
      colocalized with microtubules in dendrites. The ARD1-NAT1 complex displayed
      acetyltransferase activity against a purified microtubule fraction in vitro.
      Inhibition of the complex limited the dendritic extension of cultured neurons.
      These findings suggest that the ARD1-NAT1 complex has acetyltransferase activity
      against microtubules in dendrites. Regulation by acetyltransferase activity is a
      novel mechanism that is required for dendritic arborization during neuronal
      development.

PMID- 19090810
TI  - Hyperglycemia induces oxidative and nitrosative stress and increases renal
      functional impairment in Nrf2-deficient mice.
AB  - The transcription factor Nrf2 regulates the expression of antioxidant genes.
      Hyperglycemia-induced oxidative stress is involved in the pathogenesis of
      diabetes and its complications. However, little is known about the protective
      role of Nrf2 in diabetes. To gain insight into the protective role of Nrf2 in
      diabetes we treated Nrf2 knockout (Nrf2 KO) mice with streptozotocin (STZ). The
      STZ Nrf2 KO mice did not develop renal hyperfiltration, which was observed in the
      STZ-treated wild-type (STZ WT) mice, but renal function gradually deteriorated
      over the 10-week observation period. Urinary excretion of nitric oxide
      metabolites and the occurrence of 8-nitroguanosine, which was detected in
      glomerular lesions, were increased in STZ Nrf2 KO mice during the early stages
      after treatment. In vivo electron paramagnetic resonance analysis revealed an
      accelerated rate of decay of the 3-carbamoyl-2,2,5,5-tetramethylpyrrolidine-1
      oxyl spin probe signal in STZ Nrf2 KO mice. The addition of superoxide dismutase
      prolonged the half-life of the signal, which suggested that increased oxygen
      radical formation occurred in the STZ Nrf2 KO mice. These results suggested that
      hyperglycemia increased oxidative and nitrosative stress and accelerated renal
      injury in the Nrf2 KO mice and that Nrf2 serves as a defense factor against some
      diabetic complications.

PMID- 19090813
TI  - On the reporting of clinical trials.

PMID- 19090812
TI  - Nuclear inner membrane fusion facilitated by yeast Jem1p is required for spindle
      pole body fusion but not for the first mitotic nuclear division during yeast
      mating.
AB  - During mating of budding yeast, Saccharomyces cerevisiae, two haploid nuclei fuse
      to produce a diploid nucleus. The process of nuclear fusion requires two J
      proteins, Jem1p in the endoplasmic reticulum (ER) lumen and Sec63p, which forms a
      complex with Sec71p and Sec72p, in the ER membrane. Zygotes of mutants defective
      in the functions of Jem1p or Sec63p contain two haploid nuclei that were closely
      apposed but failed to fuse. Here we analyzed the ultrastructure of nuclei in jem1
      Delta and sec71 Delta mutant zygotes using electron microscope with the freeze
      substituted fixation method. Three-dimensional reconstitution of nuclear
      structures from electron microscope serial sections revealed that Jem1p
      facilitates nuclear inner-membrane fusion and spindle pole body (SPB) fusion
      while Sec71p facilitates nuclear outer-membrane fusion. Two haploid SPBs that
      failed to fuse could duplicate, and mitotic nuclear division of the unfused
      haploid nuclei started in jem1 Delta and sec71 Delta mutant zygotes. This
      observation suggests that nuclear inner-membrane fusion is required for SPB
      fusion, but not for SPB duplication in the first mitotic cell division.

PMID- 19090814
TI  - The impact of fibrinolytic therapy for ST-segment-elevation acute myocardial
      infarction.
AB  - As privileged witnesses of the initiation and widespread use of reperfusion
      therapy the authors review the history of fibrinolytic therapy and of tissue
      plasminogen activator (t-PA) more particularly and the current indications for
      its use in the era of mechanical reperfusion.

PMID- 19090816
TI  - Effects of thawing temperature and post-thaw dilution on the quality of cat
      spermatozoa.
AB  - The present study aimed to compare cat sperm quality after thawing using two
      different temperatures (37 and 70 degrees C) and to investigate the effects of
      post-thaw dilution on the sperm quality and longevity of ejaculated cat
      spermatozoa. Six ejaculates of each of six male cats were collected using an
      electroejaculator (total 36 ejaculates). The semen was frozen in 0.25-ml straws
      using a Tris egg yolk extender containing Equex STM paste. Four straws prepared
      from each ejaculate were thawed at four different occasions; (i) at 37 degrees C
      for 15 s, (ii) at 37 degrees C for 15 s and diluted 1 : 2 with Tris buffer (v/v),
      (iii) at 70 degrees C for 6 s, (iv) at 70 degrees C for 6 s and diluted 1 : 2
      with Tris buffer (v/v). The percentages of motile spermatozoa, the scores of
      progressive motility, the percentages of spermatozoa with intact plasma membrane
      (using SYBR-14/EthD-1 stains) and intact acrosome (using fluorescein
      isothiocyanate conjugated peanut agglutinin/propidium iodide stains) were
      evaluated in fresh semen at 0, 2, 4 and 6 h after thawing. The thawing
      temperature had no effect on any sperm parameters throughout the incubation
      period (p > 0.05). The dilution after thawing improved sperm motility,
      progressive motility and acrosome integrity (p < 0.05). The thawing of cat
      spermatozoa and subsequently diluting with Tris buffer resulted in an immediate
      (at 0 h) overall (combined over temperature) percentage of motile sperm of 64.8
      +/- 10.7 (mean +/- SD), a score of progressive motility of 4.0 +/- 0.5, a
      percentage of spermatozoa with intact plasma membrane of 64.4 +/- 12.1 and intact
      acrosome of 44.8 +/- 20.2. In conclusion, frozen cat semen can be thawed either
      at 37 or 70 degrees C and post-thaw dilution is recommended to reduce the toxic
      effect of some ingredients in the extender during post-thaw incubation.

PMID- 19090817
TI  - The effect of season on semen characteristics and freezability in Bos indicus and
      Bos taurus bulls in the southeastern region of Brazil.
AB  - The objectives of this study were to evaluate the effects of season in southeast
      of Brazil comparing genotypes on semen characteristics, freezability and
      peripheral plasma concentrations of testosterone. Ejaculates of five Bos indicus
      bulls and six Bos taurus bulls were evaluated over a period of 27 months, which
      was divided into winter (July, August, September), spring (October, November,
      December), summer (January, February, March) and autumn (April, May, June). Semen
      was evaluated according to standard procedures for ejaculate volume, sperm
      concentration, gross-motility, progressive motility and sperm morphology. After
      preparing and freezing the ejaculates according to commercial procedures, the
      straws were stored in liquid N(2) until post-thaw evaluation. Ejaculate volume,
      sperm concentration, gross-motility, progressive sperm motility, vigor and
      morphological sperm defects were significantly influenced by season and genotype
      (p < 0.05). Heat tolerance was better in B. indicus bulls than in B. taurus bulls
      characterized by lower values of sperm abnormalities throughout the observation
      period. The highest values were recorded for abnormal heads followed by
      cytoplasmatic droplets in B. taurus bulls. The proportion of ejaculates which
      were eliminated before freezing for reasons of bad quality was lower in the B.
      indicus bulls. Temporal changes in peripheral plasma testosterone concentrations
      were higher in B. indicus bulls than in B. taurus bulls not revealing seasonal
      influences. The results of this study show clear genotype differences regarding
      semen quality. Freezability of B. taurus semen varies considerably throughout the
      year, leading to a high proportion of eliminated ejaculates. Collecting semen
      from B. taurus bulls during the summer in an artificial insemination centre may
      not be profitable.

PMID- 19090818
TI  - Effect of docosahexaenoic acid on quality of cryopreserved boar semen in
      different breeds.
AB  - During the cryopreservation process, the level of polyunsaturated fatty acids,
      especially docosahexaenoic acid (DHA), in the sperm plasma membrane decreases
      significantly because of lipid peroxidation, which may contribute to sperm loss
      quality (i.e. fertility) of frozen-thawed semen. The aim of this study was to
      investigate the effect of supplementation of DHA (fish oil) in freezing extender
      II on frozen-thawed semen quality. Semen from 20 boars of proven motility and
      morphology, were used in this study. Boar semen was split into four groups, in
      which the lactose-egg yolk (LEY) extender used to resuspend the centrifuged sperm
      pellet was supplemented with various levels of fish oil to reach DHA level of 1X
      (group I, control, no added fish oil), 6X (group II), 12X (group III) and 18X
      (group IV). Semen solutions were frozen by using a controlled rate freezer. After
      cryopreservation, frozen semen was thawed and evaluated for progressive motility,
      viability by using SYBR-14/Ethidiumhomodimer-1 (EthD-1) staining and acrosome
      integrity by using FITC-PNA/EthD-1 staining. There was a significantly higher (p
      < 0.001) percentage of progressive motility, viability and acrosome integrity in
      DHA (fish oil) supplemented groups than control group. Generally, there seemed to
      be a dose-dependent effect of DHA, with the highest percentage of progressive
      motility, viability and acrosome integrity in group-III. In conclusion,
      supplementation of the LEY extender with DHA by adding fish oil was effective for
      freezing boar semen as it resulted in higher post-thaw plasma membrane integrity
      and progressive motility.

PMID- 19090819
TI  - Ovarian follicular dynamics. A review with emphasis on the bovine species. Part
      II: Antral development, exogenous influence and future prospects.
AB  - During an oestrous cycle, a cohort of antral follicles develops into--depending
      on the species--one or more ovulatory follicles. The bovine oestrous cycle is
      characterized by two to three such cohorts or growth waves, only the last of
      which will result in an ovulation. In every growth wave, several antral follicles
      are recruited for development. Recruited follicles are subjected to a selection
      process, whereby ever decreasing levels of follicle stimulating hormone (FSH) are
      available to the FSH dependent follicles. In the cow, a single follicle from the
      cohort will acquire dominance. The ability of the dominant follicle to prosper
      under basic FSH levels is ascribed to a transition in hormone dependency from FSH
      to luteinizing hormone. The exact follicle selection mechanism remains, however,
      to be elucidated. The beginning of this article focuses on the recruitment,
      selection and dominance phases in antral follicle development. Subsequently, the
      conditions leading to successful maturation and ovulation are discussed. The next
      section expounds upon the mechanisms for exogenous modulation of follicular
      dynamics with the aim of superovulation/superstimulation, and finally prospective
      future research directions are sketched.

PMID- 19090820
TI  - In vitro culture and differentiation of buffalo (Bubalus bubalis) spermatogonia.
AB  - The objective of this study was to develop a culture system which could support
      buffalo spermatogonia differentiation into spermatids in vitro. Testes from 3- to
      5-month-old buffaloes were decapsulated and seminiferous tubules were
      enzymatically dissociated to recover spermatogonia and sertoli cells. The cells
      were cultured in modified Dulbecco modified Eagle medium supplemented with
      different concentrations of foetal bovine serum, retinol, testosterone for 2
      months at 37 degrees C. Spermatogonia and sertoli cells were identified with an
      antibody against c-kit or GATA4, respectively. The viability of spermatogonia in
      the media supplemented with different concentrations of serum was all
      significantly higher (p < 0.05) compared with that in the medium without serum. A
      paired or A-aligned spermatogonia and spermatogonial colonies (AP-positive) were
      observed after 7-10 days of culture and spermatid-like cells with a flagellum (6
      8 microm) appeared after 30 days of culture. For cultured conditions, retinol
      could not significantly promote the formation of spermatid-like cells (p > 0.05),
      whereas supplementation of testosterone could significantly promote (p < 0.05)
      the formation of spermatid-like cells after 41 days of culture. The expression of
      the spermatid-specific marker gene (PRM2) was identified after 30 days of culture
      by RT-PCR. Yet, the transition protein 1 (TP1, a haploid makers) was not
      detected. Meanwhile, spermatids developed in vitro were also confirmed by Raman
      spectroscopy. These results suggest that buffalo spermatogonia could
      differentiate into spermatids in vitro based on the analysis of their morphology,
      PRM2 expression and Raman spectroscopy. Yet, the normality of the spermatid-like
      cells was not supported by TP1 expression.

PMID- 19090822
TI  - Quality and fertilizing ability in vivo of sex-sorted stallion spermatozoa.
AB  - Little information is available on the quality of stallion spermatozoa after sex
      sorting. The objectives of the present study were to assess the quality of sex
      sorted stallion spermatozoa and determine its fertilizing ability after
      hysteroscopic low dose insemination. Ejaculates from four stallions were
      collected and sorted by a MoFlo SX flow cytometer/sperm sorter. Before and after
      sorting, spermatozoa were evaluated for motility by Computer Assisted Sperm
      Analysis, viability (SYBR 14-propidium iodide), mitochondrial function (JC-1) and
      acrosomal status (fluorescein isothiocyanate Pisum sativum agglutinin
      conjugated). A fertility trial was carried out on four mares (seven oestrous
      cycles) by hysteroscopic insemination, depositing 5 x 10(6) X-bearing
      spermatozoa. Sex sorting resulted in a significant decrease (p < 0.001) in all
      motility characteristics. Sperm viability and percentage of spermatozoa with
      functional mitochondria were not affected by the sorting process, while the
      percentage of reacted spermatozoa was higher (p < 0.01) for non-sorted than
      sorted spermatozoa. Pregnancy rate was 28.6% (2/7) after low dose hysteroscopic
      insemination. Only one pregnancy was carried to term with the birth of a healthy
      filly. In conclusion, despite the reduction in sperm motility, sex sorting did
      not impair stallion sperm viability and mitochondrial activity immediately post
      thaw; moreover, the sexed spermatozoa retained the ability to fertilize in vivo.

PMID- 19090823
TI  - Is a delayed treatment with GnRH, HCG or progesterone beneficial for reducing
      embryonic mortality in buffaloes?
AB  - The aims of this study were to verify the efficacy of delayed hormonal treatments
      performed on day 25 post-insemination on pregnancy rate at 45 and 70 days in
      buffalo. The trial was performed on 385 buffaloes synchronized by the Ovsynch/TAI
      protocol and submitted to artificial insemination (AI). Twenty-five days after
      AI, pregnant animals were assigned to four treatments: (1) GnRH agonist (n = 52),
      12 microg of buserelin acetate; (2) hCG (n = 51), 1500 IU of human chorionic
      gonadotrophin; (3) Progesterone (n = 47), 341 mg of P4 intramuscular (im) every 4
      days for three times; (4) Control (n = 54), treatment with physiological saline
      (0.9% NaCl). Milk samples were collected on days 10, 20 and 25 after AI in all
      buffaloes to determine progesterone concentration in whey by radioimmunoassay
      method. Statistical analysis was performed by anova. Pregnancy rate on day 25
      after AI was 52.9%, but declined to 41.8% by day 45, indicating an embryonic
      mortality (EM) of 21%. If only control group is considered, the incidence of EM
      was 38.9%. Pregnant buffaloes had higher (p < 0.01) progesterone concentrations
      on day 20 and 25 after AI than both non-pregnant buffaloes and buffaloes that
      showed EM. The treatments on day 25 increased (p < 0.01) pregnancy rate, although
      in buffaloes with a low whey progesterone concentration on day 20 and 25 after AI
      (n = 22); all treatments were ineffective to reduce EM.

PMID- 19090824
TI  - Induction of ovulation of ovulatory size non-ovulatory follicles and initiation
      of ovarian cyclicity in summer anoestrous buffalo heifers (Bubalus bubalis) using
      melatonin implants.
AB  - This study was conducted on summer anoestrous buffalo heifers to monitor the
      efficacy of melatonin for induction of ovulation and ovarian cyclicity. During
      pre-treatment period of 24 days, the ovarian dynamics of five cycling and 10
      summer anoestrous heifers was monitored on each alternate day using a transrectal
      ultrasound scanner. Thereafter, during treatment period, these 10 anoestrous
      heifers along with additional seven anoestrous heifers were randomly allocated
      into non-implanted (n = 5) and implanted (n = 12, one melatonin implant/50 kg, 18
      mg melatonin/implant) group. Non-implanted heifers were monitored on each
      alternate day till the confirmation of second-ovulation in implanted heifers. Pre
      treatment period revealed the presence of dominant follicles in anoestrous
      heifers which attained the diameter comparable with ovulatory follicles of
      cycling heifers but failed to ovulate and regressed. Between 6 and 36 days (15.3
      +/- 2.9 days) post-treatment, all the implanted heifers (p < 0.05) exhibited
      ovulation of dominant follicles; however none of the non-implanted heifers
      ovulated during the corresponding period. The first-interovulatory period in
      implanted heifers ranged between 8 and 28 days (18.0 +/- 1.8 days). The implanted
      heifers with short (<or=16 days) interovulatory period had short-lived corpus
      luteum (CL) that had smaller diameter and secreted less progesterone (p < 0.05).
      The diameter of CL was large (p < 0.05) and plasma progesterone was high (p <
      0.05) following second-ovulation compared with first-ovulation in implanted
      heifers. In conclusion, using melatonin implants, ovulatory size nonovulatory
      follicles observed in summer anoestrous buffalo heifers can be successfully
      ovulated to initiate ovarian cyclicity.

PMID- 19090825
TI  - Effects of activin A on the in vitro development and mRNA expression of bovine
      embryos cultured in chemically-defined two-step culture medium.
AB  - The purpose of the present study was to evaluate the effects of activin A on the
      developmental competence of in vitro fertilized (IVF) bovine embryos derived from
      a two-step defined culture system (C1/C2 medium) during the early or later stages
      of embryo development. To evaluate the effects of activin A on transcriptional
      levels, we analysed genes related to blastocyst hatching and implantation and to
      activin signalling pathway in IVF embryos. Cumulus-oocyte complexes were matured
      for 22 h and fertilized in vitro. Presumptive zygotes were cultured in the
      presence or absence of activin A during early (0-120 h, C1) or later (120-192 h,
      C2) stages. Although the developmental competence of embryos cultured with
      activin A in C1 medium was not significantly different from their corresponding
      controls, development to blastocysts (22.4% vs 34.7%; p < 0.05) and the
      blastocyst hatching rate (9.3% vs 22.4%; p < 0.05) in C2 medium supplemented with
      100 ng/ml activin A were significantly higher than in the control group. To
      evaluate the effect of activin A on transcription, the relative expression levels
      of genes related to blastocyst hatching and implantation (Na/K-ATPase, E-cad and
      Glut-1) as well as activin signalling pathway (ActRII, ActRIIB and Smad2) were
      analysed. Compared to control medium, gene expression of Na/K-ATPase, E-cad, Glut
      1, ActRII and ActRIIB was increased in medium supplemented with activin A. In
      conclusion, this study suggests that activin A, during the later stage of in
      vitro bovine embryo development, can enhance in vitro development of embryos by
      increasing hatching rates and affecting expression levels of genes related to
      hatching and implantation in defined culture medium.

PMID- 19090826
TI  - Effects of superovulation with oFSH and norgestomet/GnRH-controlled release of
      the LH surge on hormone concentrations, and yield of oocytes and embryos at
      specific developmental stages.
AB  - The objective of this study was to evaluate a new superovulation procedure with
      oFSH after temporary suppression of the endogenous LH surge by norgestomet
      followed by administration of GnRH, to collect bovine oocytes and embryos at
      specific developmental stages. Since 1999, our research group applies this
      superovulation procedure with controlled release of the endogenous LH surge. The
      objective of this study is to verify if this procedure is reliable for collection
      of oocytes and embryos at specific time points of development and if it produces
      a sufficient number of both oocytes and embryos of good quality. This procedure
      was validated regarding to hormonal characteristics, superovulatory response and
      both oocyte and embryo yield at different times of in vivo development. The
      results demonstrate that the procedure used to control the occurrence of the pre
      ovulatory LH surge was effective in 92% of the animals (n = 238) and even in 99%
      of the animals the oocytes and embryos were collected at the intended stage of
      development. The superovulatory response and both oocyte, embryo yield and
      quality were similar to the average yield in Europe reported by Association
      Europeenne de transfert embryonnaire (AETE). In conclusion, this superovulation
      procedure provides a valid tool to collect oocytes and embryos at specific time
      points of development.

PMID- 19090827
TI  - Effect of polymorphisms in four candidate genes for fertility on litter size in a
      German pig line.
AB  - We carried out an SNP discovery project in pigs for candidate genes playing
      potentially important roles in embryonic development. Using eight pigs one each
      from eight breeds (Meishan, Mangalitza, Duroc, Pietrain, German Landrace,
      Hampshire, Husum Red Pied, German Large White), 36 SNPs were identified in
      intronic sequences of 21 porcine candidate genes based on sequencing of PCR
      products. The primer pairs were designed using porcine EST sequences allowing
      amplification of introns. These SNPs were tested for their association with the
      number of piglets born alive in German Large White sows using a discordant
      approach. Significant effects (p < 0.001 and p < 0.05, respectively) of intronic
      SNPs on litter size were found for four genes: mitogen-activated protein kinase
      kinase kinase 3 (MAP3K3), vascular endothelial growth factor receptor (KDR),
      erbb2 interacting protein (ERBB2IP) and peroxisome proliferator-activated
      receptor delta (PPARD). These SNPs can be further tested in upcoming association
      studies for their influence on litter size in different breeds using larger
      sample sizes.

PMID- 19090829
TI  - Efficacy of a treatment with hCG 4 days after AI to reduce pregnancy losses in
      lactating dairy cows after synchronized ovulation.
AB  - Content The objective of the study was to investigate whether a treatment with
      hCG 4 days after AI could reduce pregnancy losses in lactating dairy cows. Cows
      of a dairy herd presented to the veterinarian in a fixed reproductive management
      protocol were treated with an Ovsynch protocol if no corpus luteum (CL) could be
      palpated per rectum (Group OV). Cows with a CL received cloprostenol (0.15 mg).
      After 2 days, these cows were treated with buserelin (0.01 mg) and received timed
      AI 16-20 h later (Group PG). In both treatment protocols, cows were assigned to
      two groups to receive 2500 IU of hCG i.v. 4 days after AI or to serve as
      untreated controls (Groups OV-hCG, OV-Control, PG-hCG and PG-Control). Pregnancy
      diagnosis was carried out 27 days after AI via ultrasonography and 39 days after
      AI by rectal palpation. Pregnancy losses were defined as cows being pregnant on
      day 27 but not pregnant on day 39 after AI. Pregnancy rate (PR) by day 27 did not
      differ among the four groups (35.4, 35.0, 37.0 and 38.0% for Groups OV-hCG, OV
      Control, PG-hCG and PG-Control, respectively). Pregnancy losses between day 27
      and day 39 after AI were smaller in hCG treated animals in summer but not in
      autumn and spring. Pregnancy rate by day 39 after AI was higher in PG than in OV
      groups, but independent of hCG-treatment. In conclusion, treatment with hCG 4
      days after AI did not significantly increase PR on 39 days after AI. A positive
      effect of hCG on pregnancy losses during the summer months warrants further
      investigation.

PMID- 19090828
TI  - Effect of different combinations of cryoprotectants on in vitro maturation of
      immature buffalo (Bubalus bubalis) oocytes vitrified by straw and open-pulled
      straw methods.
AB  - This study was designed to evaluate effects of different combinations of
      cryoprotectants on the ability of vitrified immature buffalo oocytes to undergo
      in vitro maturation. Straw and open-pulled straw (OPS) methods for vitrification
      of oocytes at the germinal vesicle stage also were compared. The immature oocytes
      were harvested from ovaries of slaughtered animals and were divided into three
      groups: (i) untreated (control); (ii) exposed to cryoprotectant agents (CPAs); or
      (iii) cryopreserved by straw and OPS vitrification methods. The vitrification
      solution (VS) consisted of 6 m ethylene glycol (EG) as the standard, control
      vitrification treatment, and this was compared with 3 m EG + 3 m dimethyl
      sulfoxide (DMSO), 3 m EG + 3 m glycerol, and 3 m DMSO + 3 m glycerol.
      Cryoprotectants were added in two steps, with the first step concentration half
      that of the second (and final) step concentration. After warming, oocyte samples
      were matured by standard methods and then fixed and stained for nuclear
      evaluation. Rates of MII oocytes exposed to CPAs without vitrification were lower
      (54.3 +/- 1.9% in EG, 47.5 +/- 3.4% in EG + DMSO, 36.8 +/- 1.2% in EG + glycerol
      and 29.9 +/- 1.0% in DMSO + glycerol; p < 0.05) than for the control group (79.8
      +/- 1.3%). For all treatments in each vitrification experiment, results were
      nearly identical for straws and OPS, so all results presented are the average of
      these two containers. The percentages of oocytes reaching telophase-I or
      metaphase-II stages were lower in oocytes cryopreserved using all treatments when
      compared with control. However, among the vitrified oocytes, the highest
      maturation rate was seen in oocytes vitrified in EG + DMSO (41.5 +/- 0.6%).
      Oocytes cryopreserved in all groups with glycerol had an overall low maturation
      rate 19.0 +/- 0.6% for EG + glycerol and 17.0 +/- 1.1% for DMSO + glycerol. We
      conclude that the function of oocytes was severely affected by both vitrification
      and exposure to cryoprotectants without vitrification; the best combination of
      cryoprotectants was EG + DMSO for vitrification of immature buffalo oocytes using
      either straw or OPS methods.

PMID- 19090831
TI  - Antimicrobial and anti-inflammatory activity of five Taxandria fragrans oils in
      vitro.
AB  - The antimicrobial activity of five samples of Taxandria fragrans essential oil
      was evaluated against a range of Gram-positive (n= 26) and Gram-negative bacteria
      (n= 39) and yeasts (n= 10). The majority of organisms were inhibited and/or
      killed at concentrations ranging from 0.06-4.0% v/v. Geometric means of MIC were
      lowest for oil Z (0.77% v/v), followed by oils X (0.86%), C (1.12%), A (1.23%)
      and B (1.24%). Despite differences in susceptibility data between oils, oils A
      and X did not differ when tested at 2% v/v in a time kill assay against
      Staphylococcus aureus. Cytotoxicity assays using peripheral blood mononuclear
      cells demonstrated that T. fragrans oil was cytotoxic at 0.004% v/v but not at
      0.002%. Exposure to one or more of the oils at concentrations of <or=0.002% v/v
      resulted in a dose responsive reduction in the production of proinflammatory
      cytokines IL-6 and TNF-alpha, regulatory cytokine IL-10, Th1 cytokine IFN-gamma
      and Th2 cytokines IL-5 and IL-13 by PHA stimulated mononuclear cells. Oil B
      inhibited the production of all cytokines except IL-10, oil X inhibited TNF
      alpha, IL-6 and IL-10, oil A inhibited TNF-alpha and IL-6, oil C inhibited IL-5
      and IL-6 and oil Z inhibited IL-13 only. IL-6 production was significantly
      inhibited by the most oils (A, B, C and X), followed by TNF-alpha (oils A, B and
      X). In conclusion, T. fragrans oil showed both antimicrobial and anti
      inflammatory activity in vitro, however, the clinical relevance of this remains
      to be determined.

PMID- 19090830
TI  - Diagnosis of toxic shock syndrome by two different systems; clinical criteria and
      monitoring of TSST-1-reactive T cells.
AB  - Two methods of TSS diagnosis were evaluated: comparison of symptoms with clinical
      criteria and monitoring for evidence of selective activation of Vbeta2(+) T cells
      by the causative toxin, TSS toxin-1 (TSST-1). Ten patients with acute and
      systemic febrile infections caused by Staphylococcus aureus were monitored for
      increase in TSST-1-reactive Vbeta2(+) T cells during their clinical courses. Nine
      of the ten patients were diagnosed with TSS based on evidence of selective
      activation of Vbeta2(+) T cells by TSST-1; however, clinical symptoms met the
      clinical criteria for TSS in only six of these nine patients. In the remaining
      patient, clinical symptoms met the clinical criteria, but selective activation of
      Vbeta2(+) T cells was not observed. Time taken to reach the diagnosis of TSS
      could be significantly shortened by utilizing the findings from tracing Vbeta2(+)
      T cells. In vitro studies showed that TSST-1- reactive T cells from TSS patients
      were anergic in the early phase of their illness. Examining selective activation
      of Vbeta2(+) T cells could be a useful tool to supplement clinical criteria for
      early diagnosis of TSS.

PMID- 19090832
TI  - Analysis of peripheral blood lymphocyte phenotypes and Th1/Th2 cytokines profile
      in the systemic immune responses of Helicobacter pylori infected individuals.
AB  - H. pylori elicits specific humoral and cellular immune responses in the mucosal
      immune system. However, the type and extent of T lymphocyte response in the
      systemic immune system is not clear for H. pylori positive patients. In this
      study, peripheral blood T lymphocyte phenotypes and serum Th1/Th2 based cytokines
      of 32 H. pylori positive patients were analyzed and compared to those of healthy
      controls. While alphabeta TCR(+) lymphocytes and their phenotype analysis were
      not significantly different to those of healthy controls, the percentage of pan
      gammadelta TCR(+) lymphocytes was up to 2.4 times greater in the H. pylori
      positive group then in healthy controls. Furthermore, significant increases in IL
      10 concentrations in serum samples of H. pylori patients indicated that their
      immune systems had switched toward a Th2 type immune response. The correlation
      between phenotype and type of T cell response in the peripheral blood during H.
      pylori infection is discussed.

PMID- 19090833
TI  - Interaction between cFLIP and Itch, a ubiquitin ligase, is obstructed in
      Trypanosoma cruzi-infected human cells.
AB  - Death receptor-mediated host cell apoptosis, a defense strategy for elimination
      by the immune system of parasite-infected cells, is inhibited by Trypanosoma
      cruzi, the causative agent of Chagas' disease. It has previously been reported by
      us that, in infected cells, T. cruzi upregulates and exploits cFLIP(L), a
      mammalian inhibitor of death receptor signaling. Here it is shown that
      ubiquitination of cFLIP(L,) leading to proteasomal degradation, is inhibited in
      parasite-infected cells. The extent of expression of Itch, a protein thought to
      be an ubiquitin ligase for cFLIP(L), was found to be equivalent in T. cruzi
      infected and in uninfected cells. However, co-immunoprecipitation analysis showed
      that the interaction between cFLIP(L) and Itch is strongly inhibited in T. cruzi
      infected cells. This unique parasite strategy, which has not been reported in any
      other pathogen-infected cells, may allow the host cell to accumulate cFLIP(L),
      eventually resulting in the inhibition of apoptosis of T. cruzi-infected cells.

PMID- 19090834
TI  - Immunoreactivity of five antigens of Mycobacterium tuberculosis in patients
      attending a public health care facility in an area with high endemicity for TB.
AB  - The objective of this study was to evaluate people attending a primary health
      clinic in Rio de Janeiro, Brazil for immunoreactivity to five Mycobacterium
      tuberculosis antigens, as these antigens are markers of immune response and
      factors associated with active TB. The serum antibody titers of different
      categories of patients (defined by microbiological and radiological
      characteristics and by response to therapy on follow-up) to 38 kDa, 16 kDa,
      MPT64, ESAT-6 and MT10.3 antigens were determined blind with ELISA. Positive
      tests to each antigen were defined with ROC analysis. OR were calculated for
      factors associated with humoral response in patients with active TB. A total of
      201 patients underwent serological testing. Patients with confirmed active TB
      responded more frequently to MPT64 (44%), 16 kDa (37.7%) and 38 kDa (36.1%). ESAT
      6 and MT10.3 were also able to distinguish people in TB groups from controls. TB
      infected subjects responded less frequently to ESAT-6 and MT10.3 (3.7% and 11%,
      respectively). Sensitivity and specificity to all antigens combined were 58.4%
      and 60.7%, respectively. Reactivity to 38 kDa and to MPT64 was more likely among
      alcohol users OR 2.61 (95%CI;1.05-6.94) and OR 3.27 (95%CI;1.33-8.15),
      respectively. 16 kDa antigen elicited a more protective response among smokers,
      OR 0.29 (95%CI; 0.10-0.83). It was concluded that reactivity to all antigens
      tested represented markers of active disease. ESAT-6 and MT10.3 could not be
      identified as markers of TB infection in this community. Sensitivity was higher
      to all antigens combined, but at a cost of lower specificity. Interestingly,
      among factors associated with positive immunoreactivity, alcohol use and smoking
      seem to polarize the humoral response in different directions. This finding
      deserves further investigation.

PMID- 19090835
TI  - Identification of a WT1 protein-derived peptide, WT1, as a HLA-A 0206-restricted,
      WT1-specific CTL epitope.
AB  - The Wilms' tumor gene WT1 is overexpressed in various kinds of hematopoietic
      malignancies as well as solid cancers, and this protein has been demonstrated to
      be an attractive target antigen for cancer immunotherapy. WT1-specific CTL
      epitopes with a restriction of HLA-A 2402 or HLA-A 0201 have been already
      identified. In the present study it has been demonstrated that a 9-mer WT1
      derived WT1(187) peptide, which had already been shown to elicit a WT1-specific
      CTL response with a restriction of HLA-A 0201, can also elicit a CTL response
      with a restriction of HLA-A 0206. In all three different HLA-A 0206(+) healthy
      donors examined, WT1(187) peptide-specific CTL could be generated from peripheral
      blood mononuclear cells, and the CTL showed cytotoxic activity that depended on
      dual expression of WT1 and HLA-A 0206 molecules. The present study describes the
      first identification of a HLA-A 0206-restricted, WT1-specific CTL epitope. The
      present results should help to broaden the application of WT1 peptide-based
      immunotherapy from only HLA-A 0201-positive to HLA-A 0206-positive cancer
      patients as well.

PMID- 19090837
TI  - Ch-ch-ch-changes.

PMID- 19090836
TI  - Identification of probiotic lactobacilli used for animal feeds on the basis of
      16S ribosomal RNA gene sequence.
AB  - The use of probiotics such as Lactobacillus in animal feeds has gained popularity
      in recent years. In this study the 16S rRNA gene sequence of L. acidophilus in
      two commercial agents which have been used in animal feeds, LAB-MOS and Ghenisson
      22, was determined. Phylogenetic tree analysis revealed that the two agents,
      strain MNFLM01 in LAB-MOS and strain GAL-2 in Ghenisson 22, belonged to L.
      rhamnosus (a member of the L. casei group) and L. johnsonii (a member of the L.
      acidophilus group), respectively. Biochemical tests assigned the two as L.
      rhamnosus and ambiguously as L. acidophilus. The data suggest that 16S rRNA gene
      sequence analysis provides more accurate identification of Lactobacillus species
      than biochemical tests and would allow quality assurance of relevant commercial
      products. The 16S rRNA gene sequences of strains MNFLM01 and GAL-2 determined in
      this study have been submitted to the DDBJ/EMBL/GenBank accession numbers under
      accession numbers AB288235 and AB295648, respectively.

PMID- 19090838
TI  - From kitchen table to electronic editorial office: the evolution of the journal.

PMID- 19090839
TI  - Analysis of throughput over 25 years.

PMID- 19090840
TI  - Reflections from the editors: a triptych.

PMID- 19090841
TI  - 2008 onwards.

PMID- 19090842
TI  - Celebrating a 25-year partnership.

PMID- 19090843
TI  - Learning and teaching retrospective.

PMID- 19090844
TI  - Practitioner commentary on: Friden, K. The librarian as a teacher: experiences
      from a problem-based setting. Health Libraries Review 1996, 13, 3-7.

PMID- 19090845
TI  - Current status and future prospects.

PMID- 19090846
TI  - Information technology: retrospective.

PMID- 19090847
TI  - Practitioner Commentary on Toth B, Muir Gray JA, Fraser V, Ward R. National
      electronic Library for Health: progress and prospects. Health Libraries Review
      2000, 17, 46-50.

PMID- 19090848
TI  - Challenges for the next 25 years.

PMID- 19090849
TI  - Using evidence in practice: retrospective.

PMID- 19090850
TI  - Practitioner commentary on Garfield E. The impact of health information delivery
      on the quality of patient care: whither medical information science? Health
      Libraries review 1985, 2 (4), 159-169.

PMID- 19090851
TI  - Current status and future prospects.

PMID- 19090852
TI  - Widening panoramas: retrospective.

PMID- 19090854
TI  - Widening panoramas: current status and future prospects.

PMID- 19090853
TI  - Practitioner Commentary on: Hoppenbrouwer, J. & Kanyengo, C.W. Current access to
      health information in Zambia: a survey of selected health institutions. Health
      Information and Libraries Journal 2007, 24, 246-256.

PMID- 19090855
TI  - Ubiquitous but unfinished: grand challenges for information retrieval.

PMID- 19090856
TI  - Future of academic and health libraries: personal perspectives.

PMID- 19090857
TI  - Viva the revolution.

PMID- 19090858
TI  - A National Health Knowledge Network to support the patient journey.

PMID- 19090859
TI  - Future visions for continuing professional development in health librarianship:
      an Australian perspective.

PMID- 19090861
TI  - A fresh look at dry weight.
AB  - The concept of dry weight (DW) is central to dialysis therapy. The most commonly
      used definition of DW is the weight below which patients become hypotensive on
      dialysis. However, this definition is dependent on patient symptoms. A more
      rigorous definition of DW is the body weight at a physiological extracellular
      volume (ECV) state. Overhydration is an excess in ECV above that found in healthy
      subjects. In healthy subjects, within extremes of salt intake, ECV may vary
      between 280 and 340 mL/kg lean body mass. Sodium accumulation is one of the many
      consequences of renal failure; it results in increased water intake and an
      increase in ECV, and an accompanying rise in blood pressure with its clinical
      sequelae, most prominently cardiovascular and cerebrovascular diseases. Recently
      characterized endogenous digitalis-like factors which are released in response to
      ECV expansion have extended this traditional picture. Efforts to reduce a
      positive sodium balance include dietary counseling and avoidance of iatrogenic
      intradialytic sodium loading, such as dialysate sodium exceeding serum levels,
      sodium profiling, and intravenous saline. Excess ECV is predominantly located in
      the interstitial compartment and must be removed during dialysis therapy by
      ultrafiltration. During this process, interstitial fluid redistributes to the
      intravascular space via uptake in the capillary bed. In addition to that
      mechanism, we propose that increased lymphatic flow into the venous system
      contributes to plasma refilling. Both clinical and technical means are used to
      assess the presence of DW. Continuous segmental calf bioimpedance is a promising
      new technology for intradialytic DW diagnosis.

PMID- 19090862
TI  - Case Report: Atheroembolic renal disease in a 72-year-old patient through
      coronary intervention after myocardial infarction.
AB  - Cholesterol embolization or atheroembolic renal disease (AERD) is an often
      underdiagnosed issue in patients featuring a prevalent risk profile. It is a
      multisystemic disease with progressive renal insufficiency due to foreign body
      reaction of cholesterol crystals flushed into a small vessel system of the
      kidneys from the arteriosclerotic plaques. The most common setting in which it
      occurs is iatrogenic after vascular catheterization and less frequent
      spontaneously. Typical clinical symptoms are delayed impairment of renal
      function, cutaneous manifestations such as livedo reticularis or purple toes with
      persistingly palpable arterial pulse, myalgia, systemic symptoms such as weight
      loss and fever, and abdominal and neurological symptoms. Diagnosis is generally
      made by clinical appearance, risk profile, and interval of time from
      intervention; a definitive diagnosis can only be made by renal biopsy. Even
      though the exact incidence is not known because most patients do not undergo
      biopsy due to older age, comorbidity, and other explanations for loss of renal
      function, it is estimated to be 4% after vascular intervention. Patient and renal
      outcome is dependent on comorbidity, risk profile, and preexisting chronic kidney
      disease (CKD). About 30% of patients are estimated to require maintenance
      dialysis and these patients have a high risk of death within 24 months after the
      first renal replacement therapy. Prognosis is also influenced by severity. The
      case reported is a 72-year-old male patient with preexisting CKD stage 3
      undergoing percutaneous coronary intervention after myocardial infarction and
      consecutive AERD with typical clinical appearance 6 weeks after the event.

PMID- 19090863
TI  - Sodium, hypertension, and an explanation of the "lag phenomenon" in hemodialysis
      patients.
AB  - Sodium balance is precisely regulated by intake and output. The kidneys are
      responsible for adjusting sodium excretion to maintain balance at varying
      intakes. Our distant ancestors were herbivores. Their diet contained little
      sodium, so they developed powerful mechanisms for conserving sodium and achieving
      low urinary excretion. About 10,000 years ago, early humans became villagers and
      discovered that food could be preserved in brine. This led to increased
      consumption of salt. High salt intake increases extracellular volume (ECV), blood
      volume, and cardiac output resulting in elevation of blood pressure. High ECV
      induces release of a digitalis-like immunoreactive substance and other inhibitors
      of Na(+)-K(+)-ATPase. As a consequence, intracellular sodium and calcium
      concentrations increase in vascular smooth muscles predisposing them to
      contraction. Moreover, high ECV increases synthesis and decreases clearance of
      asymmetrical dimethyl-l-arginine leading to inhibition of nitric oxide (NO)
      synthase. High concentration of sodium and calcium in vascular smooth muscles,
      and decreased synthesis of NO lead to an increase in total peripheral resistance.
      Restoration of normal ECV and blood pressure are attained by increased glomerular
      filtration and decreased sodium reabsorption. In some individuals, the kidneys
      have difficulty in excreting sodium, so the equilibrium is achieved at the
      expense of elevated blood pressure. There is some lag time between reduction of
      ECV and normalization of blood pressure because the normal levels of Na(+)-K(+)
      ATPase inhibitors and asymmetrical dimethyl-l-arginine are restored slowly. In
      dialysis patients, all mechanisms intended to increase renal sodium removal are
      futile but they still operate and elevate blood pressure. The sodium balance must
      be achieved via dialysis and ultrafiltration. Blood pressure is normalized a few
      weeks after ECV is returned to normal, i.e., when the patient reaches dry body
      weight. This is called the "lag phenomenon."

PMID- 19090864
TI  - Fatal cerebritis and brain abscesses following a nontraumatic subdural hematoma
      in a chronic hemodialyzed patient.
AB  - Staphylococcus aureus is the leading cause of bacteremia in hemodialysis
      dependent patients that can lead to metastatic abscesses with poor outcome. We
      report a case of a 65-year-old chronic hemodialyzed male patient who developed
      cerebritis and brain abscesses complicating a spontaneous subdural hematoma,
      following Staphylococcus aureus bacteremia related to infected arteriovenous
      fistula. In spite of adequate antibiotherapy and several surgical brain
      drainages, our patient did not survive. Prevention of S. aureus is highly
      important in hemodialysis patients.

PMID- 19090865
TI  - Heparin leak from a hemodialysis catheter causing major bleeding, ultimately
      leading to transplant rejection and death.
AB  - Leakage of hemodialysis catheter-locking solutions into the circulation has been
      reported in in vitro and in vivo studies, although there have been few reports of
      serious clinical adverse events. We describe a case of heparin leak from a
      hemodialysis catheter, which caused significant clinical bleeding requiring
      multiple transfusions and may have ultimately been responsible for the patient's
      death after transplantation.

PMID- 19090866
TI  - Cultural comparison of symptoms in patients on maintenance hemodialysis.
AB  - Although symptoms are common and frequently severe in patients on maintenance
      hemodialysis, little is known about the relationship between cultural background
      and symptom burden. The aim of this study was to explore differences in the
      prevalence and severity of symptoms between American and Italian hemodialysis
      patients. We administered the 30-item Dialysis Symptom Index to American and
      Italian patients receiving maintenance hemodialysis during routine dialysis
      sessions. The prevalence and severity of individual symptoms were compared
      between patient populations, adjusting for multiple comparisons. Multivariable
      logistic regression and ordinal logistic regression were used to assess the
      independent associations of cultural background with the prevalence and severity
      of symptoms, respectively. We enrolled 75 American and 61 Italian patients.
      American patients were more likely to be black (36% vs. 0%, P<0.001) and diabetic
      (53% vs. 13%, P<0.001). Italian patients were more likely to report decreased
      interest in sex, decreased sexual arousal, feeling nervous, feeling irritable,
      and worrying (P<0.001, respectively). Adjustment for demographic and clinical
      variables had no impact on these cultural differences in symptom prevalence. The
      median severity of 11 symptoms including muscle soreness, muscle cramps, and
      itching was greater among Americans (P<0.001, respectively), although nearly all
      of these differences were rendered nonstatistically significant with adjustment
      for race, diabetes, and/or Kt/V. Italian patients receiving chronic hemodialysis
      report a greater burden of symptoms than American patients, particularly those
      related to sexual dysfunction and psychosocial distress. These findings suggest
      that cultural background may affect adaptation to chronic hemodialysis therapy.

PMID- 19090867
TI  - Costs of managing anemia with erythropoiesis-stimulating agents during
      hemodialysis: a time and motion study.
AB  - Use of erythropoiesis-stimulating agents (ESAs) presents a significant time and
      cost burden in the management of anemia of chronic kidney disease (CKD). We
      conducted a prospective, observational, activity-based costing study to estimate
      the health care personnel time and resulting direct medical costs associated with
      administering epoetin 3 times weekly to patients with end-stage renal disease on
      dialysis. The study was conducted at 5 US hemodialysis centers. The personnel
      time and costs were derived from time and motion observations. Predicted time and
      cost savings were modeled for switching patients to once-monthly ESA therapy.
      Patients also completed a survey questionnaire to assess their level of CKD
      knowledge and information needs. Total per-patient-per-year (PPPY) time expended
      on anemia management with epoetin averaged 608 minutes (range 512-915 minutes),
      with an average PPPY cost of $548 (range $342-$651). Use of a once-monthly ESA,
      compared with epoetin, could decrease average PPPY time expenditure by 79% (127
      minutes [range 96-173 minutes]) and reduce PPPY costs by 81% ($104 [range $79
      $136]). The patient questionnaire reported insufficient education on CKD. Use of
      a once-monthly ESA to correct anemia in dialysis patients may provide substantial
      time, resource, and cost savings compared with current treatment practices.

PMID- 19090868
TI  - Correlates affecting survival in chronic hemodialysis patients: the combined
      impact of albumin and high hemoglobin levels on improving outcomes, local and
      national results.
AB  - While national mortality rates for end-stage renal disease (ESRD) patients remain
      high, for the past 4 years, lower than expected local mortality rates have been
      consistently seen in our facilities. Because of these progressive improvements in
      mortality rates, a study of 687 hemodialysis patients over a 4-year period, 2003
      through 2006, was undertaken to analyze which factors may be contributing to the
      enhanced survival rates. We also examined the partially overlapping United States
      Renal Data System clinical performance measures national data sets of
      hemodialysis patients for 2001 to 2004. Proportional hazards and logistic
      regression models were used to determine significant predictors of short-term
      survival. Variables tested included hemoglobin (Hb), albumin, calcium,
      phosphorus, infections, hospitalizations, URR, Kt/V, erythropoietic stimulating
      agents (epoetin-alpha) use, and comorbid conditions. The local and national
      models identified albumin, Hgb, and hospitalization as statistically significant
      predictors of survival. Local models also found years of dialysis as a
      significant predictor. Locally, there was a 69-fold increase from 16.1
      deaths/1000 patient years for albumin > or =4.0 with Hgb> or =14.0 to 1115.9
      deaths/1000 patient-years for albumin <3.5 with Hgb<11.0. The increase nationally
      is a 4-fold increase from 96 deaths/1000 patient-years for albumin > or =4.0 with
      Hgb> or =14.0 to 406 deaths/1000 patient-years for albumin <3.5 with Hgb<11.0.
      There was no evidence that higher erythropoietic stimulating agents dose levels
      were associated with higher mortality rates, independent of the other significant
      factors. In conclusion, the findings indicate that individually higher Hgb and
      albumin levels are associated with increased survival, and when higher Hgb levels
      are in association with high albumin levels, the survival rates and
      hospitalizations are synergistically improved.

PMID- 19090869
TI  - Infective spondylodiscitis in patients on high-flux hemodialysis and on-line
      hemodiafiltration.
AB  - Infective spondylodiscitis (ISD) is a rare but potentially devastating condition
      in hemodialysis (HD) patients. Reports are limited especially in patients
      receiving high-flux HD and hemodiafiltration (HDF). In a retrospective analysis,
      13 patients on our maintenance high-flux HD/HDF program were identified as having
      has infective spondylodiscitis over a 10-year period (1997-2006), an incidence of
      approximately 1 episode every 215 patient-years. The incidence was around 3 times
      higher in patients dialyzing with tunnelled central venous catheters (TCVC) than
      in those with arteriovenous fistulae. Affected patients were elderly (mean age 70
      years) and had multiple comorbidities. Access problems, particularly TCVC
      infection, were common in the months preceding it's onset. Tunnelled central
      venous catheter removal during these episodes did not necessarily prevent it.
      Diagnosis was based on a history of back pain, raised C-reactive protein,
      positive blood cultures, and characteristic magnetic resonance findings. Many
      patients were apyrexial and had normal white cell counts. In our patients on high
      flux HD/hemodiafiltration, its incidence appears comparable to that in
      conventional HD settings. No patients had infection with waterborne organisms.
      Blood cultures were positive in 77%. Gram-positive organisms predominated,
      particularly Staphylococcus aureus. The major route of infection was
      hematogenous, with the most likely source the venous access. All received
      antibiotics for 6 to 12 weeks or until death. Only 2 patients underwent surgical
      drainage. Mortality was high (46%) and predicted by the development of
      complications, and by pre-existing cardiovascular comorbidity. Prevention, using
      strategies to reduce the prevalence of bacteremia, including limiting the use of
      TCVC, should be an overriding aim.

PMID- 19090870
TI  - Paraoxonase-1 (PON1) activity as a risk factor for atherosclerosis in chronic
      renal failure patients.
AB  - Paraoxonase is a high-density lipoprotein-associated enzyme and has been shown to
      reduce the susceptibility to low-density lipoprotein peroxidation. This study
      aimed to investigate the activity of serum paraoxonase in uremic patients on
      hemodialysis (HD) and in the predialysis period, and to evaluate the correlations
      of vascular disease with paraoxonase activity. Thirty patients with chronic renal
      failure (CRF) undergoing HD (group 1), 30 patients with CRF under conservative
      treatment (group 2), and 30 healthy controls (group 3) were included. Basal, salt
      stimulated, and arylesterase activity were tested by UV spectrophotometry. Serum
      lipid parameters were determined. B-Mode Doppler ultrasound was used to assess
      common carotid intima-media thickness (IMT). Basal paraoxonase, salt-stimulated,
      and arylesterase activity showed no significant difference between group 1 and
      group 2. However, it was significantly lower in group 1 and in group 2 than
      controls. Carotid IMT was significantly higher in group 1 than group 2 and both
      were significantly higher than controls. Basal paraoxonase-1 (PON1), salt
      stimulated PON1, and arylesterase activity correlate with BUN, but only basal
      PON1 and salt-stimulated PON1 correlate with serum albumin. Linear regression
      showed that the most significant determinant of carotid IMT was PON1 arylesterase
      activity in group 1 and arylesterase activity and basal PON1 activity in group 2.
      Patients with CRF, whether under HD or conservative treatment, have reduced basal
      and stimulated paraoxonase activities, and this could be an important factor
      causing increased vascular disease in those patients. Modifying this factor can
      be of great value to protect against this common complication.

PMID- 19090872
TI  - Hemodialysis cost in Tehran, Iran.
AB  - The purpose of this study was to assess the health service cost of hemodialysis
      (HD) delivered at hospitals in Iran as a developing country with a well-defined
      program of renal replacement therapy. A cost analysis was performed from the
      viewpoint of the 2 hospitals, with 3 shifts and full chairs, on current practice
      for dialysis maintenance. Cost and patient data were collected in 2006 and from
      April 1 to May 31, 2007, respectively. A total of 22,464 HD sessions were
      performed and 247 patients were studied during the study period. The reference
      year for the value of USD for different mentioned costs was 2006. Health care
      sector costs associated with each HD session were estimated at US$78.87. Most of
      the total maintenance expenditure was made up of medical supplies (36.19%), with
      dialyzers as the major cost driver. Staff salaries represented 17% of the cost
      and fixed direct capital costs accounted for 21.4%. Of the family members, 32.4%
      accompanied their patients. The mean cost for transportation of patients and
      accompanied person was US$3.15 +/- 2.83 and US$1.5 +/- 0.29, respectively. These
      findings are important in the light of limited available resources coupled with
      the increasing prevalence of kidney failure. A major attempt should also be made
      to increase peritoneal dialysis coverage as in some centers we cannot keep all
      chairs full, especially in some vast areas. It is highly recommended to place
      initial focus on strategies and treatments that slow disease progression, to
      postpone renal replacement therapy to save resources.

PMID- 19090871
TI  - Linking Centers for Medicare & Medicaid Services data with prospective DCOR trial
      data: methods and data comparison results.
AB  - The Dialysis Clinical Outcomes Revisited (DCOR) trial was a large randomized,
      multicenter 3-year trial comparing the effects of sevelamer with calcium-based
      binders on mortality, hospitalization, morbidity, and medical costs in
      hemodialysis subjects. Dialysis Clinical Outcomes Revisited was prospectively
      designed to link subjects to the Centers for Medicare & Medicaid Services End
      Stage Renal Disease (CMS ESRD) database to collect additional baseline
      characteristic data and to enhance outcome evaluation. Subjects were linked to
      the CMS ESRD database by means of an algorithm using several patient identifiers.
      Some baseline characteristic data were collected exclusively from the CMS ESRD
      database. Mortality and hospitalization end points were obtained from the CMS
      ESRD database and compared with similar data collected prospectively into a case
      report form (CRF) database. Of the 2103 patients who participated in the DCOR
      study, 2101 were successfully linked to the CMS ESRD database. Patient baseline
      data showed that treatment groups were well-balanced, except that a higher
      proportion of subjects in the calcium-based binder group had atherosclerotic
      heart disease. Calculated mortality rates were similar between databases, but
      more deaths were identified in the CMS than in the CRF database. These additional
      deaths were verified through several sources. More hospitalizations were also
      detected in the CMS than in the CRF database. The CMS database was a good source
      of death end points and hospitalization occurrence. Linking patients to the data
      rich CMS ESRD database allowed assessment of additional important secondary end
      points at a relatively low cost compared with prospective data collection.

PMID- 19090873
TI  - Does empiric treatment with fluoroquinolones delay the diagnosis of tuberculosis
      in patients with hemodialysis?

PMID- 19090874
TI  - The statement on home blood pressure monitoring: a mild critique.

PMID- 19090875
TI  - Efficacy, safety, and pharmacokinetics of candesartan cilexetil in hypertensive
      children aged 6 to 17 years.
AB  - This 4-week randomized, double blind, placebo-controlled study (N=240), 1-year
      open label trial (N=233), and single-dose pharmacokinetic study (N=22) evaluated
      candesartan cilexetil (3 doses) in hypertensive children aged 6 to 17 years.
      Seventy-one percent were 12 years of age or older, 71% were male, and 47% were
      black. Systolic (SBP)/diastolic (DBP) blood pressure declined 8.6/4.8-11.2/8.0 mm
      Hg with candesartan and 3.7/1.8 mm Hg with placebo (P<.01 compared to placebo for
      SBP and for the mid and high doses for DBP; placebo-corrected 4.9/3.0-7.5/6.2 mm
      Hg). The slopes for dose were not, however, different from zero (P>.05). The
      response rate (SBP and DBP <95th percentile) after 1 year was 53%. The
      pharmacokinetic profiles in 6- to 12- and 12- to 17-year-olds were similar and
      were comparable to adults. Eight candesartan patients discontinued treatment
      because of an adverse event. Candesartan is an effective, well-tolerated
      antihypertensive agent for children aged 6 to 17 years and has a pharmacokinetic
      profile that is similar to that in adults.

PMID- 19090876
TI  - Blood pressure control by drug group in the Antihypertensive and Lipid-Lowering
      Treatment to Prevent Heart Attack Trial (ALLHAT).
AB  - Blood pressure (BP) control rates and number of antihypertensive medications were
      compared (average follow-up, 4.9 years) by randomized groups: chlorthalidone,
      12.5-25 mg/d (n=15,255), amlodipine 2.5-10 mg/d (n=9048), or lisinopril 10-40
      mg/d (n=9054) in a randomized double-blind hypertension trial. Participants were
      hypertensives aged 55 or older with additional cardiovascular risk factor(s),
      recruited from 623 centers. Additional agents from other classes were added as
      needed to achieve BP control. BP was reduced from 145/83 mm Hg (27% control) to
      134/76 mm Hg (chlorthalidone, 68% control), 135/75 mm Hg (amlodipine, 66%
      control), and 136/76 mm Hg (lisinopril, 61% control) by 5 years; the mean number
      of drugs prescribed was 1.9, 2.0, and 2.1, respectively. Only 28%
      (chlorthalidone), 24% (amlodipine), and 24% (lisinopril) were controlled on
      monotherapy. BP control was achieved in the majority of each randomized group-a
      greater proportion with chlorthalidone. Over time, providers and patients should
      expect multidrug therapy to achieve BP <140/90 mm Hg in a majority of patients.

PMID- 19090877
TI  - Effects of calcium channel blockers on proteinuria in patients with diabetic
      nephropathy.
AB  - Diabetic nephropathy management should include the use of an angiotensin
      converting enzyme inhibitor (ACEI) or an angiotensin receptor blocker with
      additional antihypertensive medications to reduce proteinuria and cardiovascular
      events. Some studies suggest that adding a nondihydropyridine rather than a
      dihydropyridine calcium channel blocker (CCB) may more effectively lower
      proteinuria. We hypothesized that a trandolapril/verapamil SR (T/V) fixed-dose
      combination (FDC) was superior to a benazepril/amlodipine (B/A) FDC for reducing
      albuminuria in 304 hypertensive diabetic nephropathy patients when treated for 36
      weeks. No statistically significant differences were observed between groups in
      the primary end point; adjusted percentage change in urinary albumin/creatinine
      ratio (UACR), which increased (mean T/V, 29.29%; mean B/A, 8.49%; difference,
      20.80%; P=.34); or in change in absolute UACR, which decreased (mean [g/g] T/V, 
      0.11; mean [g/g] B/A, -0.08; difference -0.03; P=.78). There were significant
      reductions in log UACR (mean change in T/V, -0.28; P<.01; mean change in B/A, 
      0.31; P<.001) and diastolic blood pressure in both groups and in systolic blood
      pressure in the B/A group. T/V was not superior to B/A for reducing UACR. Both
      ACEI/CCB FDCs may reduce albuminuria; in the case of T/V, this appears to be
      independent of systolic blood pressure reduction in patients who had previously
      been treated and had baseline blood pressure levels of 142/77 mm Hg.

PMID- 19090878
TI  - National utilization of antihypertensive medications from 2000 to 2006 in the
      Veterans Health Administration: focus on thiazide diuretics.
AB  - The authors sought to determine the prescribing practices of clinicians treating
      veterans with hypertension. A descriptive analysis was performed using a national
      pharmacy database of patients with a diagnosis of hypertension receiving
      antihypertensive medication in the fiscal years 2000 to 2006. Angiotensin
      converting enzyme inhibitors were the most frequently prescribed antihypertensive
      class, with utilization increasing from 56.0% in fiscal year 2000 to 63.2% of
      patients in 2006. Utilization of thiazide-type diuretics increased from 31.9% of
      patients in fiscal year 2000 to 42.0% in 2006. When patient comorbidities were
      taken into consideration, 48.1% of patients defined as having uncomplicated
      hypertension had at least one prescription for a thiazide diuretic in fiscal year
      2006. Utilization by monotherapy and combination therapy were also evaluated. The
      trends in utilization allowed for identification of areas in which a change in
      prescribing practices may improve blood pressure control and health outcomes in
      the Veterans Health Administration.

PMID- 19090879
TI  - Sex differences in the hypertensive population with chronic ischemic heart
      disease.
AB  - Cardiopatia Isquemica Cronica e Hipertension Arterial en la Practica Clinica en
      Espana (CINHTIA) was a survey designed to assess the clinical management of
      hypertensive outpatients with chronic ischemic heart disease. Sex differences
      were examined. Blood pressures (BP) was considered controlled at levels of
      <140/90 or <130/80 mm Hg in diabetics (European Society of Hypertension/European
      Society of Cardiology 2003); low-density lipoprotein cholesterol (LDL-C) was
      considered controlled at levels <100 mg/dL (National Cholesterol Education
      Program Adult Treatment Panel III). In total, 2024 patients were included in the
      study. Women were older, with a higher body mass index and an increased
      prevalence of atrial fibrillation. Dyslipidemia, smoking, sedentary lifestyle,
      and peripheral arterial disease were more frequent in men. In contrast, diabetes,
      left ventricular hypertrophy, and heart failure were more common in women. BP and
      LDL-C control rates, although poor in both groups, were better in men (44.9% vs
      30.5%, P<.001 and 33.0% vs 25.0%, P<.001, respectively). Stress testing and
      coronary angiography were more frequently performed in men.

PMID- 19090880
TI  - Cardiovascular risks of dipping status and chronic kidney disease in elderly
      Japanese hypertensive patients.
AB  - Chronic kidney disease (CKD) increases the risk of cardiovascular events and is
      often associated with the nondipping pattern of blood pressure (BP). We evaluated
      ambulatory BP, CKD, and the incidence of cardiovascular events in 811 older
      hypertensive patients. CKD and the dipping pattern increased the risk of
      cardiovascular events independent of the 24-hour systolic BP level (CKD: hazard
      ratio [HR], 2.37; 95% confidence interval [CI], 1.24-4.54; nondippers: HR, 2.16;
      95% CI, 1.19-3.91; extreme dippers: HR, 2.38; 95% CI, 1.17-4.83). However, after
      adjustment for covariates that included CKD, the risk in nondippers was
      insignificant (HR, 1.83; 95% CI, 0.998-3.34; P=.051), while the risk in extreme
      dippers remained (HR, 2.59; 95% CI, 1.26-5.32; P=.009) (CKD: HR, 1.81; 95% CI,
      0.93-3.54; P=.081). Patients with CKD have an increased risk of cardiovascular
      events. CKD and other cardiovascular risk factors may account for some of the
      increased risk in nondippers, but it does not explain the higher risk in extreme
      dippers.

PMID- 19090881
TI  - A young hypertensive woman with a rare diagnosis of middle aortic syndrome.

PMID- 19090882
TI  - Late acceleration of treated uncontrolled hypertension.

PMID- 19090883
TI  - What should the physician do when creatinine increases after starting an
      angiotensin-converting enzyme inhibitor or an angiotensin receptor blocker?

PMID- 19090884
TI  - Analysis of recent papers in hypertension Jan Basile , MD , Senior Editor.

PMID- 19090885
TI  - ASH: renaissance of a society -- a movement of vigorous renewal.

PMID- 19090888
TI  - Special thanks.

PMID- 19090889
TI  - Accuracy of impression techniques for implants. Part 1--Influence of transfer
      copings surface abrasion.
AB  - PURPOSE: This study evaluated the influence of surface abrasion of transfer
      copings to obtain a precise master cast for a partially edentulous restoration
      with different inclinations. MATERIALS AND METHODS: Replicas (N = 30) of a metal
      matrix (control group) containing two implants at 90 degrees and 65 degrees in
      relation to the benchtop were obtained using a polyether impression material and
      three impression techniques: square impression copings splint with dental floss
      and autopolymerizing acrylic resin (TRS), square impression copings abraded with
      aluminum oxide (TA), and square impression copings abraded with aluminum oxide
      and adhesive-coated (TAA). The replicas obtained in type V stone were
      digitalized, and the images were exported to AutoCAD software to perform the
      readings of possible degree alterations in implant inclinations. The results were
      submitted to analysis of variance (ANOVA) and Tukey test (alpha < 0.05). RESULTS:
      Comparing the techniques with regard to the 90 degrees implant inclination, no
      statistical difference was observed between the three techniques and the control
      group. Analyzing the three techniques with regard to the 65 degrees implant
      inclination, no significant difference was seen between technique TA and the
      control group. CONCLUSIONS: Technique TA presented more accurate master casts
      than TRS and TAA techniques. The angulated implant (65 degrees ) tended to
      generate more imprecise master casts than implants perpendicular to the surface.

PMID- 19090890
TI  - American Board of Prosthodontics.

PMID- 19090891
TI  - Let's talk about statistics and prosthodontics research: Part 3, presentation of
      results.

PMID- 19090892
TI  - Editorial.

PMID- 19090893
TI  - Venous needle dislodgement: how to minimise the risks.
AB  - Although haemodialysis (HD) has become a routine treatment, adverse side effects,
      and occasionally life threatening clinical complications, still happen. Venous
      needle dislodgment (VND) is one of the most serious accidents that can occur
      during HD. If the blood pump is not stopped, either by activation of the
      protective system of the dialysis machine or manually, the patient can bleed to
      death within minutes. Fatal and near-fatal blood loss due to VND have been
      described in the literature (ECRI 1998; Sandroni 2005; Mactier & Worth 2007), but
      published reports represent only the tip of the ice berg, as such incidents are
      normally handled at a local or national level. The European Dialysis and
      Transplant Nurses Association/European Renal Care Association (EDTNA/ERCA) has
      produced 12 practice recommendations to help reduce the risk of VND and detect
      blood leakage as early as possible. A poster summarising these recommendations
      has been created (Van Waeleghem et al. 2008).

PMID- 19090894
TI  - Research into pain perception with arteriovenous fistula (avf) cannulation.
AB  - Patients with end-stage renal failure (ESRF) undergoing haemodialysis (HD) are
      repeatedly exposed to stress and pain from approximately 300 punctures per year
      to their arteriovenous fistula (AVF). Repeated AVF punctures lead to a
      considerable degree of pain, due to the calibre and length of the bevel of
      fistula needles. Pain is a sensitive, emotional and subjective experience. The
      objective of this study was to measure pain associated with AVF needling. The
      analogue visual scale (AVS) divided into 10 equal parts (0 indicating lack of
      pain, and 10 unbearable pain) was used. Patients(7) perceptions were measured in
      three different HD sessions. Pain was considered mild during AVF needling. The
      buttonhole technique caused a mean degree of pain of 2.4 (+/-1.7), compared to
      3.1 (+/-2.3) using the conventional ropeladder technique. Although without
      reaching a statistically significant difference, diminished pain was associated
      with the buttonhole technique.

PMID- 19090895
TI  - Raising awareness of chronic kidney disease among South Asians and primary care:
      the ABLE project.
AB  - Established renal failure as a complication of diabetes in 10 times greater in
      South Asians than in Caucasians. The objectives were: (1) to develop methods to
      increase community awareness and (2) to support general practices to improve
      chronic kidney disease (CKD) detection and management. The methods include: 1.
      Action research approach. 2. Public health education programme. 3. Audit in
      control and intervention practices. 4. Post-intervention focus group study
      determining changes in knowledge. 5. Evaluation and dissemination in community
      and primary care. RESULTS: An evaluation of innovative resources and peer
      educator model demonstrated a positive feedback, increased knowledge and evidence
      of positive lifestyle change. Intervention with the practices has demonstrated
      the need to improve some aspects of CKD management. CONCLUSION: This unique
      initiative has helped to identify practical strategies to address CKD awareness
      in these communities. However, the successful elements need to become part of
      mainstream National health Service and not just delivered by short-term projects.

PMID- 19090896
TI  - Atheromatous renovascular disease: overview and challenges.
AB  - Atheromatous renovascular disease (ARVD) is a common and challenging disease. It
      is increasingly associated with chronic kidney disease (CKD) and end-stage renal
      disease (ESRD), hypertension and cardiovascular burden. Controversy exists
      regarding the safest investigative methods as well as optimum treatment of this
      condition. In this review, we provide an overview of ARVD and discuss the
      challenges still remaining.

PMID- 19090897
TI  - CE: Continuing Education article. Patient management in chronic kidney disease
      stages 4 to 5.
AB  - This is the second article in a two part Continuing Education (CE) series on
      managing patients with Chronic Kidney Disease (CKD). The first CE article
      addressed the management of patients during CKD stages 1 to 3. This article will
      focus on the management of patients during CKD stages 4 to 5. Nephrology nurses
      and other healthcare professionals play an important role in the monitoring and
      management of the many physical symptoms that patients present with during stages
      4 to 5. During these stages the healthcare team must provide psychological
      support along with educating patients and their families/carers regarding their
      treatment options including renal replacement therapy, conservative treatment and
      withdrawal of dialysis.

PMID- 19090898
TI  - Impact of heparin locking frequency on preventing temporary dialysis catheter
      dysfunction in haemodialysis patients.
AB  - A prospective analysis was conducted comparing dysfunction attributable to
      catheter thrombosis in subjects who received a heparin catheter lock three times
      a week (n = 15) to those who received a heparin lock six times a week (n = 15)
      immediately after the insertion of a temporary haemodialysis catheter. Thrombus
      related catheter removal occurred in two patients in control but no patients in
      the experiment group. Heparin locking six times a week was found to be effective
      in prolonging the mean of the first day where difficulty was experienced in
      aspiration. It also prevented any possible difficulty in catheter flushing.
      Increased locking frequency prevents any thrombus accumulation within the
      temporary catheter, while it has limited but significant preventive effect on
      thrombus accumulated around the catheter.

PMID- 19090899
TI  - Blood borne virus-innovative approach to evaluate, prevent cross-transmission in
      dialysis units.
AB  - Large public health interventions to control infectious disease outbreaks are
      common, but rigorous evaluation to improve the quality and effectiveness of these
      is rarely undertaken. This project aimed to prevent blood borne virus (BBV) cross
      transmission in dialysis units. Following an incident concerning the diagnosis of
      acute Hepatitis B in a haemodialysis patient, possibly from healthcare associated
      acquisition, a multifaceted and multidisciplinary investigation was conducted
      involving consumers, health professionals and administrations. The results of
      this investigation were then used to produce practical operational guidelines for
      planning and future interventions. To date, there has been no incidence reported
      of any cross-transmission of BBV amongst our dialysis population. The actions
      implemented can be utilised by other departments in preventing other bacterial or
      viral outbreaks.

PMID- 19090900
TI  - Advanced glycation end products in renal failure: an overview.
AB  - The article aims to present an overview of the existing knowledge on advanced
      glycation end products (AGE). They are moieties that bind to proteins, but also
      lipids and nuclear acids. AGE are formed during glycation and oxidative stress.
      Accumulation of AGE occurs especially in diabetes and chronic renal failure and
      plays a major pathogenetic role. The deleterious effects of AGE result from cross
      linking of proteins and activation of the receptor for advanced glycation end
      products. AGE accumulation can be noninvasively assessed by the skin
      autofluorescence reader. In diabetics, the skin autofluorescence predicts cardiac
      mortality and the occurrence of macro- and microvascular complications. In
      patients on haemodialysis, skin autofluorescence is highly elevated and predicts
      mortality. After renal transplantation AGE accumulation is lower than during
      haemodialysis, but still remains elevated and is a strong risk factor for chronic
      renal transplant dysfunction. Some of the potential methods to intervene with AGE
      accumulation are discussed in this article.

PMID- 19090901
TI  - The use of pharmaceuticals for dialysis patients. How well do we know our
      patients' allergies?
AB  - Medication allergies are potentially important but usually poorly documented in
      patient medical records. Allergy awareness by clinical staff may be low in the
      haemodialysis population despite their regular attendance for treatment sessions.
      A cross-sectional study of 25 patients in a satellite unit was performed. All
      known allergies were not documented in 36% of patients despite the patients being
      known to the renal service for more than five years. 81% of allergies were
      medication allergies. The rest were due to topical agents. 57% (affecting 8
      patients) of the medication allergies related to antibiotics (especially
      penicillin). Four patients had multiple antibiotic allergies. The nature and
      severity of these allergies was not well documented. This study demonstrates that
      despite being under long-term care there remains incomplete information, which is
      vital for optimal safe practice. Without such information, the potential for
      adverse events and anaphylaxis is significant in a population that is exposed to
      numerous pharmaceutical agents and are frequently prescribed antibiotics.
      Medication histories should be comprehensively re-evaluated regularly and
      prescribing should not occur unless the allergy box is completed.

PMID- 19090906
TI  - Effects of tooth loss and denture wear on tongue-tip motion in elderly dentulous
      and edentulous people.
AB  - The purpose of this study was to clarify quantitatively the differences in tongue
      tip motion among the dentulous elderly people and also among the elderly
      edentulous, both with and without their dentures and, to identify the influence
      of tooth loss and denture wear on tongue-tip motion. Fourteen young dentulous
      people, 12 elderly dentulous people and 13 elderly edentulous people participated
      in this study. Subjects were asked to swallow a 10 mL barium sulfate solution
      three times. The elderly edentulous people were asked to swallow the solution
      while wearing dentures and with dentures removed. Functional swallowing was
      recorded on cine-film with a digital subtraction angiography system. Lateral
      cinefluorography images were obtained from seated subjects. Using a cine
      projector, the movements of the tongue surface were traced as dots and lines
      frame by frame on a single tracing sheet within a definite period of time from
      the beginning of the oral phase to the end of the pharyngeal phase. With counting
      the number of 'trajectories' of tongue-tip motion, tongue movements were
      classified as 'stable' and 'hyperactive' types. The results was that
      significantly more 'hyperactive' type subjects were found among the elderly
      edentulous who were not wearing dentures (12 of 13) compared with the dentulous
      young (1 of 14), the elderly dentulous (1 of 13) or the elderly edentulous
      wearing dentures (1 of 13) (P < 0.001). The tongue-tip motion for the
      'hyperactive' type was very complex and the tongue-tip anchoring against the
      palate was always instable.

PMID- 19090907
TI  - Morphological and molecular changes in denture-supporting tissues under
      persistent mechanical stress in rats.
AB  - The purpose of this study was to determine the effects of mechanical compression
      on the palatal mucosa using an experimental palatal base. The palatal base was
      either pressed onto (stress group) or not pressed onto (fit group) rat palatal
      mucosa. Blood flow was measured and the animals were sacrificed 6-72 h later for
      analysis. The expression of heat shock protein 70 (HSP70), vascular endothelial
      growth factor (VEGF) and proliferation cell nuclear antigen (PCNA) was
      characterized by immunohistochemical staining. For morphometric analysis,
      connective tissues were divided into bone side and epithelial side tissues. The
      ratio of PCNA-positive cells (PCNA score) was calculated, and the expressions of
      mRNA encoding HSP70 and VEGF was evaluated. Whereas blood flow in the stress
      group showed ischaemia, none was found in the fit group. Proliferation cell
      nuclear antigen scores on the bone side were higher than on the epithelial side
      in the stress group (P < 0.05). Heat shock protein 70- and VEGF-positive cells
      were observed under compression conditions, particularly in the periosteum. In
      the stress group, the expressions of mRNA encoding HSP70 and VEGF were highest at
      12 h (P < 0.05). These results suggest that mechanical compression of the palatal
      plate induces ischaemia, and that cells in the underlying denture-supporting
      tissue, which includes the periosteum, synthesize HSP70 and VEGF to maintain
      homeostasis under these conditions.

PMID- 19090908
TI  - Investigation of infraorbital nerve injury following zygomaticomaxillary complex
      fractures.
AB  - The aim of this study was to investigate the severity of infraorbital nerve
      injury following zygomaticomaxillary complex fractures and to estimate the
      treatment methods facilitating its functional recovery. A total of 478 patients
      with unilateral zygomaticomaxillary complex fractures were treated. Infraorbital
      nerve sensory disturbances were diagnosed in 64.4% of the patients. Injury of the
      infraorbital nerve was expressed as asymmetry index, which was calculated as a
      ratio between the affected side and the intact side electric pain detection
      thresholds at the innervation zone skin before treatment and 14 days, 1, 3, 6 and
      12 months postoperatively. A mean asymmetry index of 0.6 +/- 0.03 and 1.9 +/- 0.5
      was registered for 57 (11.9%) patients with hyperalgesia and for 251 (52.5%)
      patients with hypoalgesia, respectively. As a result of retrospective analysis of
      infraorbital nerve sensory disturbances and its functional recovery, infraorbital
      nerve injury severity was classified as mild, moderate and severe. It was found
      that the dynamics and outcome of the functional infraorbital nerve recovery
      depend on the severity of the injury and the presence of infraorbital canal
      damage. Function was completely recovered within 3 months after treatment in
      cases with mild nerve injury. In moderate cases, complete recovery was seen
      within 6 months and in 34.6% of the severe cases, within a 12-month period after
      treatment when infraorbital nerve decompression was performed according to the
      stated indication. Treatment based on infraorbital nerve injury classification
      offers a better prognosis for complete recovery of the infraorbital nerve
      function.

PMID- 19090909
TI  - Low-level laser therapy improves bone repair in rats treated with anti
      inflammatory drugs.
AB  - Nowadays, selective cyclooxygenase-2 non-steroidal anti-inflammatory drugs have
      been largely used in surgical practice for reducing oedema and pain. However, the
      association between these drugs and laser therapy is not known up to now. Herein,
      the aim of this study was to evaluate the action of anti-COX-2 selective drug
      (celecoxib) on bone repair associated with laser therapy. A total of 64 rats
      underwent surgical bone defects in their tibias, being randomly distributed into
      four groups: Group 1) negative control; Group 2) animals treated with celecoxib;
      Group 3) animals treated with low-level power laser and Group 4) animals treated
      with celecoxib and low-level power laser. The animals were killed after 48 h, 7,
      14 and 21 days. The tibias were removed for morphological, morphometric and
      immunohistochemistry analysis for COX-2. Statistical significant differences (P <
      0.05) were observed in the quality of bone repair and quantity of formed bone
      between groups at 14 days after surgery for Groups 3 and 4. COX-2
      immunoreactivity was more intense in bone cells for intermediate periods
      evaluated in the laser-exposed groups. Taken together, such results suggest that
      low-level laser therapy is able to improve bone repair in the tibia of rats as a
      result of an up-regulation for cyclooxygenase-2 expression in bone cells.

PMID- 19090910
TI  - Possible impact of inflammatory status on C-telopeptide pyridinoline cross-links
      of type I collagen and osteocalcin levels around oral implants with peri
      implantitis: a controlled clinical trial.
AB  - Detection of progression level of peri-implantitis may help in the prevention of
      oral implant failure. C-telopeptide pyridinoline crosslinks of Type I collagen
      (ICTP) and osteocalcin (OC) are specific markers of bone turnover and bone
      degradation. Determination of the ICTP and OC levels in the peri-implant sulcus
      fluid (PISF) may predict the metabolic and/or inflammatory changes in the peri
      implant bone. The aim of this clinical study was to evaluate ICTP and OC levels
      in the PISF for oral implants with and without peri-implant bone destruction and
      correlate these levels with the traditional clinical peri-implant parameters
      (probing depth, plaque index, gingival index and gingival bleeding time index)
      and radiographic bone level measurements. Fifteen patients with 30 peri-implant
      sites with bone destruction (radiographic bone loss) and health were included.
      Clinical parameters were measured and PISF was collected from the sites. Peri
      implant sulcus fluid ICTP and OC levels were detected by radioimmunoassay
      technique from PISF samples. All clinical parameters demonstrated a significant
      increase in peri-implantitis sites compared with healthy sites. The PISF volume
      of the peri-implantitis sites was also significantly higher than of the healthy
      peri-implant sites. Although not statistically significant, a trend of increase
      was demonstrated in ICTP PISF samples sampled from peri-implantitis sites
      compared with healthy sites. A significant increase was noticed for OC PISF level
      in peri-implantitis sites compared with healthy ones. As well as peri-implant
      clinical measurements, volumetric changes at PISF may be counted as an important
      clinical parameter to distinguish the bone destruction sites from healthy sites
      around oral implants.

PMID- 19090911
TI  - Melatonin reduces stress-activated/mitogen-activated protein kinases in spinal
      cord injury.
AB  - Permanent functional deficits following spinal cord injury (SCI) arise from both
      mechanical injury and from secondary tissue reactions involving inflammation. The
      mitogen-activated protein kinases (MAPKs) play a critical role in cell signaling
      and gene expression. MAPK family includes three major members: extracellular
      signal regulated kinase (ERK), p38, and c-Jun N-terminal kinase (JNK),
      representing three different signaling cascades. Moreover, various studies have
      clearly shown that high-mobility group box 1 (HMGB1) protein is implicated as a
      putative danger signal involved in the pathogenesis of a variety of inflammatory
      conditions including autoimmunity, cancer, trauma and hemorrhagic shock, and
      ischemia-reperfusion injury. Recently, we have reported that the pineal secretory
      product melatonin exerts important anti-inflammatory effects in an experimental
      model of SCI induced by the application of vascular clips (force of 24 g) to the
      dura after a four-level T5-T8 laminectomy. However, no reports are available on
      the effect of melatonin on MAPK signaling pathways and HMGB1 expression in SCI.
      The aim of the present study was to evaluate whether the melatonin protective
      effect observed in SCI is related to the regulation of MAPK signaling pathways
      and HMGB1 in mice. In this study we demonstrate the efficacy of treatment with
      the melatonin in SCI in mice in reducing (a) motor recovery, (b) activation of
      MAPKs p38, JNK and ERK1/2, (c) tumor necrosis factor-alpha expression, and (d)
      expression of HMGB1. We propose that melatonin's ability to reduce SCI in mice is
      also related to a reduction in MAPK signaling pathways and HMGB1 expression.

PMID- 19090912
TI  - Endogenous melatonin provides an effective circadian message to both the
      suprachiasmatic nuclei and the pars tuberalis of the rat.
AB  - The suprachiasmatic nuclei (SCN) distribute the circadian neural message to the
      pineal gland which transforms it into a humoral circadian message, the nocturnal
      melatonin synthesis, which in turn modulates tissues expressing melatonin
      receptors such as the SCN or the pars tuberalis (PT). Nuclear orphan receptors
      (NOR), including rorbeta and rev-erbalpha, have been presented as functional
      links between the positive and negative loops of the molecular clock. Recent
      findings suggest that these NOR could be the initial targets of melatonin's
      chronobiotic message within the SCN. We investigated the role of these NOR in the
      physiological effect of endogenous melatonin on these tissues. We monitored
      rorbeta and rev-erbalpha mRNA expression levels by quantitative in situ
      hybridization after pinealectomy. Pinealectomy had no effect on NOR circadian
      expression rhythms in the SCN in 8-day pinealectomized (PX) animals. However in
      animals PX for 3 months, significant desynchronization between per1 and per2
      transcription patterns appeared. These results suggest that endogenous melatonin
      could sustain the circadian rhythmicity and the phase relationship between the
      molecular partners of the SCN circadian system on a long-term basis. On the other
      hand, pinealectomy decreased the level and abolished the rhythmicity of NOR mRNA
      expression in the PT. These effects were partially prevented by daily melatonin
      administration in the drinking water. These results show that NOR can be
      regulated by the melatonin circadian rhythm in the PT and could be the link
      between the physiological action of melatonin and the core of the molecular
      circadian clock in this tissue.

PMID- 19090913
TI  - Melatonin alters cell death processes in response to age-related oxidative stress
      in the brain of senescence-accelerated mice.
AB  - We studied the effect of age and melatonin on cell death processes in brain
      aging. Senescence-accelerated prone mice 8 (SAMP8) and senescence-accelerated
      resistant mice (SAMR1) at 5 and 10 months of age were used as models of the
      study. Melatonin (10 mg/kg) or its vehicle (ethanol at 0.066%) was administered
      in the drinking water from 1 to 9 months of age. Neurodegeneration, previously
      shown in the aged brain of SAMP8 and SAMR1 at 10 months of age, may be due to a
      drop in age-related proteolytic activities (cathepsin D, calpains, and caspase
      3). Likewise, lack of apoptotic and macroautophagic processes were found, without
      apparent modification by melatonin. However, the caspase-independent cell death,
      owing to high p53 and apoptosis-inducing factor (AIF) levels, might be an
      alternative pathway of cell death in the aged brain. The main effects of
      melatonin treatment were observed in the aged SAMR1 mice; in this strain we
      observed a marked increase in antioxidant activity (catalase and superoxide
      dismutase). Likewise, a key antioxidant role of apoptosis-related proteins, Bcl-2
      and AIF, was suggested in the aged brain of SAM mice, which was clearly
      influenced by melatonin. Moreover, the age-related increase of lysosomal activity
      of cathepsin B and a lysosomal membrane-associated protein 2 supports the
      possibility of the maintenance of lysosomal viability in addition to age-related
      impairments of the proteolytic or macroautophagic activities. The effectiveness
      of melatonin against the oxidative stress-related impairments and apoptosis
      during the aging process is, once more, corroborated in this article.

PMID- 19090914
TI  - Chemical Biology & Drug Design 2008: transition, scholarship and faith.

PMID- 19090915
TI  - The structure of glycosaminoglycans and their interactions with proteins.
AB  - Glycosaminoglycans (GAGs) are important complex carbohydrates that participate in
      many biological processes through the regulation of their various protein
      partners. Biochemical, structural biology and molecular modelling approaches have
      assisted in understanding the molecular basis of such interactions, creating an
      opportunity to capitalize on the large structural diversity of GAGs in the
      discovery of new drugs. The complexity of GAG-protein interactions is in part due
      to the conformational flexibility and underlying sulphation patterns of GAGs, the
      role of metal ions and the effect of pH on the affinity of binding. Current
      understanding of the structure of GAGs and their interactions with proteins is
      here reviewed: the basic structures and functions of GAGs and their
      proteoglycans, their clinical significance, the three-dimensional features of
      GAGs, their interactions with proteins and the molecular modelling of heparin
      binding sites and GAG-protein interactions. This review focuses on some key
      aspects of GAG structure-function relationships using classical examples that
      illustrate the specificity of GAG-protein interactions, such as growth factors,
      anti-thrombin, cytokines and cell adhesion molecules. New approaches to the
      development of GAG mimetics as possible new glycotherapeutics are also briefly
      covered.

PMID- 19090916
TI  - Effects of hydrophobicity on the antifungal activity of alpha-helical
      antimicrobial peptides.
AB  - We utilized a series of analogs of D-V13K (a 26-residue amphipathic alpha-helical
      antimicrobial peptide, denoted D1) to compare and contrast the role of
      hydrophobicity on antifungal and antibacterial activity to the results obtained
      previously with Pseudomonas aeruginosa strains. Antifungal activity for
      zygomycota fungi decreased with increasing hydrophobicity (D-V13K/A12L/A20L/A23L,
      denoted D4, the most hydrophobic analog was sixfold less active than D1, the
      least hydrophobic analog). In contrast, antifungal activity for ascomycota fungi
      increased with increasing hydrophobicity (D4, the most hydrophobic analog was
      fivefold more active than D1). Hemolytic activity is dramatically affected by
      increasing hydrophobicity with peptide D4 being 286-fold more hemolytic than
      peptide D1. The therapeutic index for peptide D1 is 1569-fold and 62-fold better
      for zygomycota fungi and ascomycota fungi, respectively, compared with peptide
      D4. To reduce the hemolytic activity of peptide D4 and improve/maintain the
      antifungal activity of D4, we substituted another lysine residue in the center of
      the non-polar face (V16K) to generate D5 (D-V13K/V16K/A12L/A20L/A23L). This
      analog D5 decreased hemolytic activity by 13-fold, enhanced antifungal activity
      to zygomycota fungi by 16-fold and improved the therapeutic index by 201-fold
      compared with D4 and represents a unique approach to control specificity while
      maintaining high hydrophobicity in the two hydrophobic segments on the non-polar
      face of D5.

PMID- 19090917
TI  - Identification of endomorphin-1 and endomorphin-2 binding sites in human mu
      opioid receptor by antisense oligonucleotide strategy.
AB  - The effects of phosphorothioate antisense oligodeoxynucleotides against exons-1, 
      2, -3 and -4 of the human mu-opioid receptor were studied in the CHO-mu-opioid
      receptor cells using aequorin luminescence-based calcium assay. All four
      antisense oligodeoxynucleotides significantly decreased the level of mu-opioid
      receptor mRNA in comparison with the non-treated cells, used as control. However,
      no statistically significant differences between antisense oligodeoxynucleotides
      were observed. antisense oligodeoxynucleotides against exon-2 attenuated
      endomorphin-1-induced intracellular calcium response in a concentration-dependent
      manner. antisense oligodeoxynucleotides against exons-1, -2, -3 and -4 inhibited
      endomorphin-2-induced intracellular calcium response in a concentration-dependent
      manner and the effect of antisense oligodeoxynucleotides against exons-3 and -4
      was most pronounced. The mismatch oligodeoxynucleotides against respective exons
      failed to exert any effect. The selective actions of antisense probes directed
      against different exons of the human mu-opioid receptor gene, that resulted, at
      the protein level, in attenuation of calcium responses induced by endomorphin-1
      and endomorphin-2, suggest that the binding sites for endomorphins are
      structurally and functionally different. The presence of functionally distinct
      binding sites might play a crucial role in the modulation of pain and may be
      important clinically.

PMID- 19090919
TI  - LigEvolutioner, a new strategy for modification and optimization of lead
      compounds in receptor/ligand complexes.
AB  - With the number of solved protein/ligand complex 3D structures growing up rapidly
      in recent years, lead modification and optimization based on the complex
      structure have received much attention in drug design community. In this study,
      we propose a novel method LigEvolutioner for the purpose of lead optimization in
      protein/ligand complexes. Using a fragment substitution strategy in the context
      of evolutionary algorithm, LigEvolutioner can analyze the complex structures
      automatically and derive several modification projects that could possibly
      improve the binding affinity of ligands. For instance, LigEvolutioner was
      employed to analyze and modify antigenic peptide ligand in human HLA
      A*0201/peptide complexes and, as a result, a peptide analogue with potential high
      affinity was designed. The structure configuration of this modified peptide is
      consistent with crystal profile and antigen presenting theory. In addition, we
      have confirmed the validity of LigEvolutioner by systematically comparing it with
      several widely used scoring methods.

PMID- 19090920
TI  - Effect of a novel series of benzothiazolo-quinazolones on epidermal growth factor
      receptor (EGFR) and biological evaluations.
AB  - A newly designed benzothiazolo-quinazolone series was synthesized by an aromatic
      amine and potassium thiocyanate in the presence of bromine in glacial acetic
      acid, and the final product was obtained by subsequent reaction with 5
      arylamido/imidoalkyl-2-chlorobenzoic acid in the presence of potassium carbonate
      and further cyclization with sulphuric acid. A preliminary radiolabelling study
      with technetium shows a promising potential for further in vivo evaluation. Anti
      bacterial, anti-viral and anti-tumor activities were evaluated for biological
      properties. Lead compounds are able to block epidermal growth factor receptor
      (EGFR) in human breast adenocarcinoma cell line, MCF-7.

PMID- 19090918
TI  - Inhibitors of tubulin assembly identified through screening a compound library.
AB  - Tubulin is the proposed target for drugs against cancer and helminths and is also
      a validated target in kinetoplastid parasites. With the aim of identifying new
      lead compounds against Leishmania sp., tubulin isolated from L. tarentolae was
      used to screen a 10 000 compound library. One compound, Chembridge No. 7992831
      (5), displayed an IC(50) of 13 microm against Leishmania tubulin in an in vitro
      assembly assay and showed a greater than threefold selectivity over mammalian
      tubulin. Another compound, Chembridge No. 9067250 (8), exhibited good activity
      against mammalian tubulin (IC(50) = 5.0 microm). This compound was also toxic to
      several cancer cell lines with IC(50) values in the region of 1 microm.
      Subsequent testing of analogues of 8 contained within the library identified two
      compounds with greater potency against mammalian tubulin (IC(50) values of 1.1
      and 2.8 microm). The more potent antitubulin agent also showed promising activity
      against cancer cell lines in vitro, with IC(50) values ranging from 0.18 to 0.73
      microm.

PMID- 19090921
TI  - Potential glucocorticoid receptor ligands with pulmonary selectivity using I-QSAR
      with the signature molecular descriptor.
AB  - We intend in this research to establish a rational method for the development of
      novel glucocorticoid receptor ligands to more effectively prevent respiratory
      inflammation. Corticosteroids, a class of steroid hormones, are naturally
      inclined to bind to the glucocorticoid receptor and, in this research, are the
      basis for exploring other novel and non-intuitive structures. To be more
      effective than currently available medications, novel compounds must be highly
      selective toward the lungs and must be inactivated when exposed to the main
      circulation, thus preventing the participation of the ligand in other systems and
      consequently reducing systemic side-effects. We look to use the inverse
      quantitative structure-activity relationship algorithm with the Signature
      molecular descriptor to generate new ligands based upon the structures and
      activities of 65 experimentally studied corticosteroids. Inverse-quantitative
      structure-activity relationship explore many possible combinations of atom
      connectivity while structural filters and other scoring approaches are used to
      predict and identify the most promising candidates for further study. Properties
      explored include high receptor binding affinity, high systemic clearance, high
      plasma protein binding and low oral bioavailability. Among more than 300 million
      potential candidates generated, 84 high priority compounds with properties
      predicted to be at least as or more effective than currently available
      corticosteroids have been identified with this procedure.

PMID- 19090922
TI  - Quantum topological QSAR models based on the MOLMAP approach.
AB  - Quantum topological molecular similarity produces a two-dimensional array of
      descriptors for each molecule while a three-dimensional array is obtained by
      placing the descriptor data matrices of a set of molecules beside each other.
      Here, we use the multiway data analysis method called molecular maps (MOLMAP) of
      atom-level properties in a new way. We transferred the three-dimensional array of
      quantum topological molecular similarity descriptors into new two-dimensional
      parameters using Kohonen networks, followed by partial least squares. Six
      different data sets were analyzed by the proposed procedure, which were
      previously analyzed (Eur. J. Med. Chem. 2006 41 862) by partial least squares
      applied to unfolded data. They include: (i) the pK(a) of imidazoles, (ii) the
      ability of a set of indole derivatives to displace [(3)H] flunitrazepam from
      binding to bovine cortical membranes, (iii) the inhibitory effect of a set of
      benzimidazoles on the influenza virus, (iv) the interaction of amides with liver
      alcohol dehydrogenase, (v) inhibition of carbonic anhydrase by sulfonamides and
      (vi) the toxicity of a set of chlorophenols. Overall, the results showed better
      statistical results compared with simple unfolding. Furthermore, variable
      important in projection plots confirmed previous findings about active centers
      and even in some cases showed more accurate results.

PMID- 19090923
TI  - Exploring QSAR for substituted 2-sulfonyl-phenyl-indol derivatives as potent and
      selective COX-2 inhibitors using different chemometrics tools.
AB  - Selective inhibition of cyclooxygenase-2 inhibitors is an important strategy in
      designing of potent anti-inflammatory compounds with significantly reduced side
      effects. The present quantitative structure-activity relationship study, attempts
      to explore the structural and physicochemical requirements of 2-sulfonyl-phenyl
      indol derivatives (n = 30) for COX-2 inhibitory activity using chemical,
      topological, geometrical, and quantum descriptors. Some statistical techniques
      like stepwise regression, multiple linear regression with factor analysis as the
      data preprocessing (FA-MLR), principal component regression analysis, and genetic
      algorithms partial least squares analysis were applied to derive the quantitative
      structure-activity relationship models. The generated equations were
      statistically validated using cross-validation and external test set. The quality
      of equations obtained from stepwise multiple linear regression, FA-MLR, principal
      component regression analysis and PLS were in the acceptable statistical range.
      The best multiple linear regression equation obtained from factor analysis (FA
      MLR) as the preprocessing step could predict 77.5% of the variance of the
      cyclooxygenase-2 inhibitory activity whereas that derived from genetic algorithms
      partial least squares could predict 84.2% of variances. The results of
      quantitative structure-activity relationship models suggested the importance of
      lipophilicity, electronegativity, molecular area and steric parameters on the
      cyclooxygenase-2 inhibitory activity.

PMID- 19090924
TI  - QSAR study of 2-(1-Propylpiperidin-4-yl)-1H-benzimidazole-4-carboxamide as PARP
      inhibitors for treatment of cancer.
AB  - Quantitative structure-activity relationship of the 2-(1-propylpiperidin-4-yl)-1H
      benzimidazole-4-carboxamide as a potent inhibitor of poly(ADP-ribose) polymerase
      for cancer treatment was studied. A suitable set of molecular descriptors was
      calculated and the genetic algorithm was employed to select those descriptors
      that resulted in the best fitted models. Excellent results were obtained
      employing multiple linear regressions and critically discussed using a variety of
      statistical parameters. Furthermore, the model was validated using leave-one-out
      and leave-group-out cross-validation, external test set and chance correlation. A
      genetic algorithm-multiple linear regression model with seven selected
      descriptors was obtained. This model, with high statistical significance (R(2) =
      0.935, Q(2)_(LOO)= 0.894, Q(2)_(LGO)= 0.875, F = 53.481), could be used to
      predict poly(ADP-ribose) polymerase inhibitor activity of the molecules.

PMID- 19090925
TI  - Identification of novel HCV RNA-dependent RNA polymerase inhibitors using
      pharmacophore-guided virtual screening.
AB  - We performed pharmacophore-guided virtual screening experiments using FlexX-Pharm
      to identify novel inhibitors of hepatitis C virus RNA-dependent RNA polymerase.
      Pharmacophore model generated from our previous analysis of the binding modes as
      well as structure-based three-dimensional quantitative structure-activity
      relationship studies of aryl diketoacid analogues was used. In pharmacophore
      guided virtual screening study, among 37 447 compounds in LeadQuest chemical
      library, 40 compounds were selected as novel candidates of hepatitis C virus RNA
      dependent RNA polymerase inhibitors, and their biological activities were
      evaluated. Especially, T29 was chosen for further development.

PMID- 19090926
TI  - Synthesis, structural characterization and biological evaluation of N-protected
      cyclopropylethylcarbamates as potential histone deacetylase inhibitor.
AB  - A simple synthesis involving a key coupling reaction and biological activity of N
      protected cyclopropylethylcarbamates (18-21) are described. The key fragments are
      amine.HCl salt (13) and acids (16 and 17) which were smoothly coupled by using 2
      (7-aza-1H-benzotriazol-1-yl)-1,1,3,3-tetramethyluroniumhexafluorophosphate in
      high yield. We have found that the in vitro growth inhibitory potency of new
      compound 19 exhibited good histone deacetylase activity.

PMID- 19090927
TI  - Synthesis and immunosuppressive activity of lipophilic amino alcohols and
      diamines.
AB  - In this work, we report the preparation and evaluation of the in vitro and in
      vivo of the immunosuppressive activity of a series of lipophilic amino alcohols
      and diamines. All compounds were evaluated for inhibition of cell proliferation,
      cytotoxicity and NO production. Compounds 9, 12, 13, 17, and 18 did not display
      inhibition of cell proliferation while decreased NO production. The two most
      potent compounds, 13 and 17, submitted to delayed-type hypersensitivity assays
      showed immunosuppressive activity.

PMID- 19090928
TI  - Novel aminomethylindole derivatives as inhibitors of pp60c-Src tyrosine kinase:
      synthesis and biological activity.
AB  - The pp60(c-Src) is one of the ubiquitously expressed Src family kinases and has
      important functions in malignant cells, including regulation of cell division,
      growth factor signaling, and movement. Therefore, investigating new small
      molecule inhibitors of pp60(c-Src) is important to discover and develop novel
      therapeutics for cancer and metastasis. Moreover, some of the small molecule
      inhibitors that do not qualify for therapeutic use may become very useful tool to
      explore the role of Src kinase in normal cells as well as in a variety of disease
      models. Our continuous efforts to find novel inhibitors of pp60(c-Src) aimed for
      therapeutic and research use, we synthesized newly designed aminomethylindole
      derivatives as novel small molecule inhibitors and investigated their inhibitory
      effect on pp60(c-Src) tyrosine kinase. Here, we report one potential inhibitor of
      the pp60(c-Src) from five active molecules of all nine compounds, which were
      synthesized and screened for the biological activity of the molecules against
      pp60(c-Src) target.

PMID- 19090929
TI  - Antibiotic awareness day.

PMID- 19090931
TI  - Introduction. Key issues surrounding the treatment of acute coronary syndromes
      (ACS).

PMID- 19090932
TI  - The rationale for and comparisons of different antiplatelet treatments in acute
      coronary syndrome.
AB  - Fundamentally, acute coronary syndromes are platelet-centric diseases, resulting
      from platelet-rich thrombi that develop at the site of vessel wall injury. In
      addition to aggregation, platelets modulate a plethora of other important
      pathophysiologic processes, including inflammation and coagulation. Therefore, a
      primary goal of therapy in the acute setting should be treatment with agents that
      provide predictable and superior platelet inhibition to prevent further ischemic
      events that develop from unchecked high platelet reactivity. Translational
      research studies of patients undergoing percutaneous revascularization have
      clearly demonstrated that adverse thrombotic outcomes are associated with high
      platelet reactivity and the latter is now emerging as a potent measurable
      cardiovascular risk factor. The intensity of antithrombotic therapy is influenced
      by patient risk. In the highest risk patients with elevated cardiac biomarkers
      indicative of myonecrosis, current guidelines support the use of early therapy
      with glycoprotein IIb/IIIa inhibition, aspirin, and clopidogrel.

PMID- 19090933
TI  - Advances in antiplatelet therapy for ACS and PCI.
AB  - Platelet activation and thrombin formation play significant roles in the
      pathophysiology of acute coronary syndrome. To overcome this pathophysiology,
      antiplatelet agents are utilized to decrease platelet aggregation and
      anticoagulants to decrease thrombin formation. Current antiplatelet agents are
      designed to inhibit various mediators of platelet activation, such as thromboxane
      A2 and adenosine diphosphate, and platelet-surface receptors (e.g., glycoprotein
      IIb/IIIa receptors). The rationale for upstream versus deferred administration of
      antiplatelet therapy in patients scheduled for percutaneous intervention and the
      current ACC/AHA guidelines for the management of patients with unstable
      angina/non-ST-segment myocardial infarction are discussed. The next-generation
      antiplatelet drugs are in various stages of clinical development, with unique
      differentiating mechanistic and pharmacokinetic properties. The newer P2Y12
      thienopyridine receptor antagonists and protease receptor inhibitor are also
      examined, in addition to the rationale of various outcome studies evaluating the
      efficacy and safety of the different agents.

PMID- 19090934
TI  - Antiplatelet therapy: anti-ischemic benefits versus bleeding risk.
AB  - Balance between efficacy and safety is a major concern in therapeutic
      interventions of patients with acute coronary syndromes. Identifying and managing
      the risks that may negatively affect this balance can potentially minimize the
      incidence of morbidity and/or mortality among patients with acute coronary
      syndromes. Unstable angina and non-ST-elevation myocardial infarction are
      potentially life-threatening disorders and a major cause of hospitalization and
      emergency medical care. At the time of presentation, the use of algorithms that
      provide reasonable assessment of a patient's risk of cardiovascular events, such
      as the Thrombolysis in Myocardial Infarction risk score, can help clinicians
      identify which patients will most likely benefit from a specific strategy. The
      ultimate goal of treatment for non-ST-elevation myocardial infarction is to
      reduce short- and long-term morbidity and mortality, as well as salvage
      myocardial cells and cardiac function. Pharmacologic intervention with
      antiplatelet and/or antithrombotic agents has proven to be effective in achieving
      this goal in numerous outcome studies. However, clinicians must balance anti
      ischemic efficacy with the need to minimize the risk of serious bleeding
      complications (e.g., hemorrhage). Issues related to safety include timing of the
      dose, duration of infusion, drug compatibility, errors in estimating a patient's
      weight and/or age, failure to adjust the dosage based upon renal function, and
      errors in drug preparation.

PMID- 19090935
TI  - "I think sex is here to stay" Groucho Marx (1890-1977).

PMID- 19090937
TI  - Eastern approaches for enhancing women's sexuality: mindfulness, acupuncture, and
      yoga (CME).
AB  - INTRODUCTION: A significant proportion of women report unsatisfying sexual
      experiences despite no obvious difficulties in the traditional components of
      sexual response (desire, arousal, and orgasm). Some suggest that nongoal-oriented
      spiritual elements to sexuality might fill the gap that more contemporary forms
      of treatment are not addressing. AIM: Eastern techniques including mindfulness,
      acupuncture, and yoga, are Eastern techniques, which have been applied to women's
      sexuality. Here, we review the literature on their efficacy. METHODS: Our search
      revealed two empirical studies of mindfulness, two of acupuncture, and one of
      yoga in the treatment of sexual dysfunction. MAIN OUTCOME MEASURE: Literature
      review of empirical sources. RESULTS: Mindfulness significantly improves several
      aspects of sexual response and reduces sexual distress in women with sexual
      desire and arousal disorders. In women with provoked vestibulodynia, acupuncture
      significantly reduces pain and improves quality of life. There is also a case
      series of acupuncture significantly improving desire among women with hypoactive
      sexual desire disorder. Although yoga has only been empirically examined and
      found to be effective for treating sexual dysfunction (premature ejaculation) in
      men, numerous historical books cite benefits of yoga for women's sexuality.
      CONCLUSIONS: The empirical literature supporting Eastern techniques, such as
      mindfulness, acupuncture, and yoga, for women's sexual complaints and loss of
      satisfaction is sparse but promising. Future research should aim to empirically
      support Eastern techniques in women's sexuality.

PMID- 19090941
TI  - Health-related quality of life instruments in studies of adult men with
      testosterone deficiency syndrome: a critical assessment.
AB  - INTRODUCTION: Health-related quality of life (HRQOL) is a multidimensional
      concept, which subjectively measures a patient's physical, social, and emotional
      well-being. This information is becoming increasingly important in policy and
      clinical decisions. With such a wide range of tools available, careful selection
      is required to ensure they adequately reflect patient's concerns. AIM: To
      critically assess HRQOL instruments used in studies of testosterone deficiency
      syndrome (TDS) to see whether they accurately measure these concerns. METHODS: A
      systematic review identified published articles. Studies were included if the
      population was adult men with TDS, with or without comorbid disease; used one or
      more HRQOL tools; and described the impact of treatment, the impact of TDS on the
      patient or the development of a questionnaire. Measurement properties and their
      use in clinical studies were described. Each study was assessed against 10
      clinical face validity criteria to evaluate whether the questionnaires reflected
      issues that were of concern to patients. MAIN OUTCOME MEASURE: Review of
      published literature. RESULTS: The study identified 29 articles that included 14
      HRQOL questionnaires selected for use in 20 intervention studies, seven studies
      of the impact of TDS on the patient, and two studies describing the development
      of a HRQOL tool. Questionnaires displayed variable measurement properties and
      only nine studies complied with more than 50% of the clinical face validity
      criteria. Disease-specific instruments achieved a higher rate of compliance and
      more often demonstrated a positive effect of treatment on HRQOL compared to
      generic instruments. CONCLUSION: Instruments used to measure HRQOL display
      variable measurement properties and often lack adequate clinical face validity.
      There are well-validated disease-specific HRQOL measures for age-related TDS, but
      none for classical TDS patients. Clinical and political decision-makers require
      HRQOL information using a combination of well-validated generic questionnaires
      and patient-focused, disease specific instruments relevant to the target TDS
      population under study.

PMID- 19090940
TI  - Sexually dimorphic effects of testosterone administration on brain
      allopregnanolone in gonadectomized rats.
AB  - INTRODUCTION: Clinical and biological evidences have shown a wide range of
      neuroactive effects of testosterone administration. AIM: Evaluation of the
      effects of 2-weeks treatment with testosterone (T), Dihydrotestosterone (DHT),
      and estradiol valerate (E2V) on brain and serum allopregnanolone (AP) in
      gonadectomized rats of both sexes. MAIN OUTCOME MEASURES: AP levels were measured
      in frontal and parietal lobe, hippocampus, hypothalamus, anterior pituitary, and
      in serum. METHODS: Eight groups of Wistar female and eight groups of Wistar male
      rats were included. For each sex, one group of fertile and one group of
      gonadectomized rats were employed as control receiving placebo. The others groups
      received subcutaneous T at the dose of 10 microg/kg/day and 100 microg/kg/day for
      female rats, and 1 mg/kg/day and 5 mg/kg/day for male rats, or DHT at the doses
      of 1 microg/kg/day, 10 microg/kg/day, and 100 microg/kg/day for females, and 0, 1
      microg/kg/day, 1 mg/kg/day and 5 mg/kg/day for males, or E2V (0.05 mg/Kg/day).
      RESULTS: Ovariectomy (OVX) and orchidectomy (OCX) induced a significant decrease
      in AP in all brain areas analyzed, as well as in serum. In OVX rats, T
      replacement, as well as E2V, significantly increased AP content in all brain
      areas and in plasma. In OCX, T and E2V did not actively result in influencing AP
      concentration in frontal and parietal lobe, while it produced a significant rise
      in AP levels in the hippocampus, hypothalamus, anterior pituitary, and serum.
      Conversely, DHT replacement had no affect on AP levels anywhere or at any
      administered dose, either in males or in female rats. CONCLUSIONS: Gender
      difference and T therapy affect brain AP synthesis/release during the
      reproductive aging. This effect becomes particularly evident in the brain of
      ovariectomized animals, where the content of this specific neurosteroid is much
      more responsive than male animals to testosterone replacement.

PMID- 19090942
TI  - PCOS, sexuality, and clitoral vascularisation: a pilot study.
AB  - INTRODUCTION: In polycystic ovarian syndrome (PCOS) women, the changes in body
      appearance (mainly obesity and hirsutism) may influence the feminine identity of
      the patients with consequent depression and sexual disturbances. AIM: To evaluate
      if lean PCOS patients present an increased incidence of depression and sexual
      dysfunction in comparison with controls and if clitoral volume and
      vascularization are influenced by circulating androgens levels. METHODS: 25 lean
      PCOS women (Group I) and 18 healthy nonhirsute volunteers (Group II) were
      submitted, on day 3-5 of the cycle, to ultrasonographic and Doppler analyses, and
      to hormonal and biochemical evaluations. MAIN OUTCOME MEASURES: Utero-ovarian and
      clitoral ultrasonographic analysis, and color Doppler evaluation of the uterine,
      stromal ovarian, and dorsal clitoral arteries. Hormonal and nitrites/nitrates
      plasma concentrations were analyzed. Each woman filled in the 2-factor Italian
      McCoy female questionnaire (MFSQ) and the Beck's Depression Inventory
      questionnaire (BDI). RESULTS: Androgens resulted, as expected, more elevated in
      PCOS patients than in controls. However, the ultrasonographic (US) assessment of
      the clitoral body volume evidenced no significant differences between PCOS
      (0.72+/-0.41 mL) and control (0.62+/-0.20 mL) patients. The resistances
      registered at the level of the dorsal clitoral artery did not show any difference
      between Group I (PI=1.55+/-0.40) and Group II (PI=1.79+/-0.38). The 2-factor
      Italian MFSQ and the BDI did not show any difference between PCOS women and
      controls. CONCLUSIONS: In PCOS women, probably, the moderate hirsutism and
      hyperandrogenism do not induce the sense of loss of feminine identity and have no
      impact on sexual self-worth and sexual satisfaction.

PMID- 19090943
TI  - Male sexual dysfunction in unconsummated marriage: long-term outcome in 417
      patients.
AB  - INTRODUCTION: Little research has been conducted about unconsummated marriage
      (UCM). AIM: To report the long-term outcome of male sexual dysfunction (MSD) in
      UCM. METHODS: From 1997 to 2008, 417 couples presented to the author with UCM.
      The mean UCM duration ranged from 1 hour to 8 years. The median follow-up was
      78.5 months. MAIN OUTCOME MEASURES: Self-reported MSD in UCM based upon clinical
      history taking. RESULTS: In 177 cases, UCM was due to erectile dysfunction (ED)
      (86), premature ejaculation (PE) (89), performance anxiety (25), vaginismus (34),
      hypodesire disorder (6), not knowing the coital technique (8), men who have sex
      with men (MSM) (2), hypogonadism (1), request by bride to delay coitus (1), and
      thick hymen (1) (more than one factor involved in many cases). In the remaining
      240 cases, UCM was due to being under social pressure to have a quick intercourse
      while relatives waited behind the door to confirm and celebrate coitus by
      checking a handkerchief that was placed beneath the bride to become bloody by
      hymen perforation. Intracavernosal injection (ICI) using papaverine +/-
      phentholamine was used in 239 cases (57.3%); 221 (92.4%) responded. The eight
      cases who did not know the coital technique responded to sex education. Of the 50
      men who were prescribed phosphodiesterase type 5 inhibitors, only 4 responded. Of
      the 26 men who received clomipramine (21) or fluoxetine (5) for PE, 2 and 1
      responded, respectively. Fourteen grooms who did not respond to treatments later
      consummated spontaneously. No treatment was given to 94 grooms, including men
      with a diagnosis of psychotic disorder, men with learning difficulties, divorcing
      patients, and men in obligatory, loveless marriages. Ten untreated patients later
      consummated spontaneously. Of the 260 patients who consummated either with
      treatment (236) or spontaneously (24), 58 (22.3%) later presented with sexual
      complaints. The remaining 202 did well at a follow-up. Of the 157 couples who did
      not respond to treatment or did not receive treatment, 62 were either divorced or
      divorcing. CONCLUSION: We strongly advise ICI as the first-line treatment of UCM.
      Oral therapies of ED and PE, vacuum constriction devices (VCD), and hymenectomy
      are of limited value. No treatment is indicated in many cases. Most grooms do
      well sexually in a long-term follow-up.

PMID- 19090944
TI  - Overactive bladder is associated with erectile dysfunction and reduced sexual
      quality of life in men.
AB  - INTRODUCTION: The prevalence of sexual dysfunction, including erectile
      dysfunction (ED), is greater in men with lower urinary tract symptoms (LUTS),
      including overactive bladder (OAB), than in men without LUTS. AIM: To evaluate
      the prevalence of ED, the impact of urinary symptoms on sexual activity and
      sexual enjoyment, and sexual satisfaction in men with OAB. METHODS: A nested case
      control analysis was performed on data from a subset of men with (cases) and
      without (controls) OAB frequency-matched for age (5-year age strata) and country
      from the EPIC study. Respondents were asked about OAB symptoms (using the 2002
      International Continence Society [ICS] definitions) and sexual activity. Sexually
      active respondents were asked about ED, sexual enjoyment, and overall
      satisfaction with their sex lives. Conditional logistic regression was used to
      assess factors associated with ED. MAIN OUTCOME MEASURES: The percentage of cases
      and controls reporting ED, a reduction in the frequency of sexual activity or
      enjoyment of sexual activity because of urinary symptoms, and overall
      satisfaction with their sex lives was determined for cases and controls. RESULTS:
      A total of 502 cases and 502 controls were matched for age strata and country.
      Significantly more cases (14%) reported reduced sexual activity because of
      urinary symptoms compared with controls (4%; P <or= 0.05). Among sexually active
      respondents, cases were significantly more likely to have ED than were controls
      (prevalence odds ratio, 1.5; 95% confidence interval, 1.1-2.2); the prevalence of
      ED was similar to that for men with hypertension or diabetes. Significantly more
      cases (15%) reported decreased enjoyment of sexual activity because of urinary
      symptoms relative to controls (2%; P <or= 0.05), and significantly fewer cases
      were satisfied with their sex lives (81% vs. 90%; P <or= 0.05). CONCLUSIONS: OAB,
      as defined by the ICS, was significantly associated with increased prevalence of
      ED, reduced sexual activity and sexual enjoyment because of urinary symptoms, and
      reduced sexual satisfaction.

PMID- 19090945
TI  - Improvement of chronic pain by treatment of erectile dysfunction.
AB  - INTRODUCTION: Pain specialists, who do not routinely examine patients regarding
      their sexual medicine problems, need to be aware that sexual problems can and do
      aggravate the patient's pain. Patients may refuse to admit suffering from
      erectile dysfunction (ED) but complain about continuous or progressive severe
      pain. These patients may be best managed by the combined team effort of a sexual
      medicine specialist and pain specialist. AIM: This report documents the
      management of three cases with long-term intractable pain after severe trauma.
      Treatment of occult ED led to significant improvement of their pain. MAIN OUTCOME
      MEASURES: The association of the treatment of uncovered ED and improvement of
      chronic severe pain. METHODS: Three case reports of patients with severe pain who
      attended a pain clinic in an academic medical center. RESULTS: Three men
      suffering from chronic pain due to severe trauma were observed for several years
      by different physicians as well as pain specialists. In spite of different
      treatments, including administration of several analgesics, psychotherapy, and
      physical therapy, pain was not alleviated. After finding ED problems, patients
      were referred to the family health clinic. Using different therapies such as
      psychosexual therapy, correction of sexual misconceptions, relaxation training,
      treatment of interpersonal difficulties, and pharmacological intervention ED was
      cured. Treatment of ED was accompanied by a significant reduction of chronic pain
      in all three patients. CONCLUSION: The present report indicates that uncovered ED
      in patients suffering from chronic pain may trigger their somatic pain or reduce
      its threshold. Significant improvement in sexual functioning may improve the pain
      and reduce its complications.

PMID- 19090946
TI  - 5-alpha reductase inhibitors and erectile dysfunction: the connection.
AB  - INTRODUCTION: Benign prostatic hyperplasia (BPH) is a common problem affecting
      middle-aged and elderly men. First-line medical therapy includes alpha 1blockers
      and 5alpha-reductase inhibitors (5ARIs), such as finasteride and dutasteride.
      5ARI use has been associated with adverse sexual outcomes, including erectile
      dysfunction (ED), ejaculatory dysfunction (EjD), and decreased libido. AIM: To
      clarify the association between sexual adverse effects (AEs) and 5ARIs through
      review of literature concerning 5ARIs and to review the proposed mechanisms of
      these effects. METHODS: A comprehensive literature review, using MEDLINE and
      PUBMED search engines, was conducted for all publications concerning 5ARIs and
      sexual AEs. MAIN OUTCOME MEASURE: Sexual adverse effects, such as ED, EjD, and
      decreased libido, were the measured outcomes of this literature review. RESULTS:
      Sexual AEs are reported in clinical trials at rates of 2.1% to 38%. The most
      common sexual AE is ED, followed by EjD and decreased libido. These effects occur
      early in therapy and attenuate over time. A proposed mechanism for sexual
      dysfunction involves decreased nitric oxide synthase activity due to decreased
      dihydrotestosterone. CONCLUSIONS: The connection between 5ARIs and sexual
      dysfunction is apparent upon review of the literature. Though theories have been
      proposed, little is known about the exact mechanisms behind 5ARI-related sexual
      dysfunction. Since the connection between 5ARIs and sexual AEs is established in
      the literature, future research should be directed toward deciphering the
      pathophysiologic mechanisms. When more basic science knowledge is attained in
      this area, the focus can shift toward prevention and treatment.

PMID- 19090947
TI  - Severe vascular complication after implantation of a three-piece inflatable
      penile prosthesis.
AB  - We report a case of acute arterial ischemia and deep venous thrombosis due to
      compression of the external iliac vein and artery by the reservoir of a three
      piece inflatable penile prosthesis.

PMID- 19090948
TI  - A Turkish study of prevalence and risk factors for low sexual function in women.

PMID- 19090949
TI  - Myofibroblasts and mechanotransduction: do forces in the tunica albuginea
      contribute to Peyronie's disease?

PMID- 19090951
TI  - On sleepy humans and sleepy rats.

PMID- 19090952
TI  - Interaction of chronic sleep restriction and circadian system in humans.
AB  - Nocturnal sleep restriction and compensation with daytime naps is common in
      today's society. In a between-participants design, we examined the effects of
      chronic (10 nights) sleep restriction on 24 h plasma melatonin profiles in
      humans. Following a baseline period with 8.2 h time in bed (TIB) for sleep,
      participants were randomized to a control (8.2 h TIB) or sleep-restriction
      condition (4.2 h TIB), with and without diurnal naps. Sleep restriction was
      achieved via delaying bedtime and advancing wake time by 2 h each relative to the
      baseline sleep period. Participants were maintained in a controlled, time
      isolated laboratory environment throughout the protocol, with light levels below
      40 lx at all times. Twenty-four hour plasma melatonin profiles were assessed at
      baseline and at the end of the sleep-restriction period, with subjects maintained
      in a constant posture protocol. Compared with the baseline assessment and the 8.2
      h TIB control group, a significant phase delay in melatonin onset (1.2 +/- 0.9 h)
      occurred in all sleep-restriction (4.2 h TIB) groups (P < 0.05). There was no
      evidence of a phase advance or shortening of the period of melatonin secretion
      associated with the advanced waking time. These results suggest that nocturnal
      light and dark exposure may be more potent in effecting circadian phase shifts
      than exposure to morning light, at least in conditions of controlled, dim
      lighting in the laboratory.

PMID- 19090953
TI  - Sleep position alters arousal processes maximally at the high-risk age for sudden
      infant death syndrome.
AB  - An impaired ability to arouse from sleep may play an important role in the
      pathogenesis of sudden infant death syndrome (SIDS). This study aimed to
      investigate the effects of prone sleeping on the nature of both induced and
      spontaneous arousal responses in infants. Thirteen healthy term infants were
      studied longitudinally at 2-4 weeks, 2-3 months and 5-6 months postnatal age. A
      pulsatile jet of air to the nostrils was used to induce arousal from both active
      sleep and quiet sleep in both prone and supine positions. For each stimulus,
      arousals were classified as sub-cortical activations and cortical arousals,
      scored using physiological and electroencephalogram changes and expressed as a
      percentage of the total number of arousals. Spontaneous arousals were similarly
      analysed. Increased proportions of cortical arousals, hence decreased proportions
      of sub-cortical activations, were observed in the prone position at 2-3 months.
      This distinct peak in the proportion of cortical arousals occurred regardless of
      sleep state and regardless of whether the arousal occurred spontaneously or was
      induced by air-jet stimulation. The nature of arousal responses in healthy term
      infants is altered in the prone sleeping position at 2-3 months after birth, the
      age where SIDS incidence is highest. We postulate that a greater propensity for
      cortical arousal may be a protective mechanism to promote complete arousal in a
      vulnerable sleeping position and/or a vulnerable period of maturation. Inadequate
      or incomplete cortical arousals may explain the increased risk of SIDS associated
      with the prone position at this age.

PMID- 19090955
TI  - Letter to the Editor re: Pressman et al. Alcohol-induced sleepwalking or
      confusional arousal as a defense to criminal behavior: a review of scientific
      evidence, methods and forensic considerations. J. Sleep Res. (2007) 16, 198-212.

PMID- 19090959
TI  - The wisdom, and madness, of crowds.

PMID- 19090960
TI  - Glomerular matrix metalloproteinases and their regulators in the pathogenesis of
      lupus nephritis.
AB  - Lupus nephritis is a major contributor to morbidity and mortality in systemic
      lupus erythematosus, but little is known about the pathogenic processes that
      underlie the progressive decay in renal function. A common finding in lupus
      nephritis is thickening of glomerular basement membranes associated with immune
      complex deposition. It has been speculated that alterations in the synthesis or
      degradation of membrane components might contribute to such changes, and thereby
      to initiation and progression of nephritis through facilitation of immune complex
      deposition. Matrix metalloproteinases (MMPs) are enzymes that are intimately
      involved in the turnover of major glomerular basement membrane constituents,
      including collagen IV and laminins. Alterations in the expression and activity of
      MMPs have been described in a number of renal diseases, suggesting their
      relevance to the pathogenesis of various glomerulopathies. The same is true for
      their natural inhibitors, the tissue inhibitor of metalloproteinase family.
      Recent data from our group have identified an increase in proteolytic activity
      within the glomerulus coinciding with the development of proteinuria in the mouse
      model of systemic lupus erythematosus. (NXB x NZW)F1 Here we review current
      understanding of MMP/tissue inhibitor of metalloproteinase function within the
      kidney, and discuss their possible involvement in the development and progression
      of lupus nephritis.

PMID- 19090961
TI  - Acute kidney injury in burns: a story of volume and inflammation.
AB  - Acute kidney injury occurs in approximately one-quarter to one-third of patients
      with major burn injury. Apart from the usual suspects - such as older age,
      severity of burn injury, sepsis and multiple organ dysfunction - volume overload
      probably has an important role in the pathogenesis of acute kidney injury.

PMID- 19090964
TI  - A bridge to transcription by RNA polymerase.
AB  - A comprehensive survey of single amino-acid substitution mutations critical for
      RNA polymerase function published in Journal of Biology supports a proposed
      mechanism for polymerase action in which movement of the polymerase 'bridge
      helix' promotes transcriptional activity in cooperation with a critical substrate
      interaction domain, the 'trigger loop'.

PMID- 19090965
TI  - Epitope spreading in animal models: array of hope in rheumatoid arthritis and
      multiple sclerosis.
AB  - The paradigm for pathogenic autoimmunity is the generation of high-titre,
      affinity-matured autoantibodies to a restricted family of autoantigens, in the
      appropriate genetic context. Genetic determinants of autoimmunity are largely
      found within the major histocompatibility complex (MHC) and the 'genotype to
      serotype to phenotype' concept is supported in a number of autoimmune diseases,
      where both genotype and serotype are well established. The serotype is
      autoantigen-driven, with evidence of epitope spreading as the disease evolves
      from asymptomatic to pathogenic autoimmunity. In rheumatoid arthritis and
      multiple sclerosis, where the autoantigens are poorly characterised, the use of
      an array in animal models may produce a hint of what happens in human disease. A
      more complete picture will be obtained from animals transgenic for human MHC,
      immunised with known human autoantigens.

PMID- 19090963
TI  - NOD-like receptors and inflammation.
AB  - The nucleotide-binding and oligomerization domain, leucine-rich repeat (also
      known as NOD-like receptors, both abbreviated to NLR) family of intracellular
      pathogen recognition receptors are increasingly being recognized to play a
      pivotal role in the pathogenesis of a number of rare monogenic diseases, as well
      as some more common polygenic conditions. Bacterial wall constituents and other
      cellular stressor molecules are recognized by a range of NLRs, which leads to
      activation of the innate immune response and upregulation of key proinflammatory
      pathways, such as IL-1beta production and translocation of nuclear factor-kappaB
      to the nucleus. These signalling pathways are increasingly being targeted as
      potential sites for new therapies. This review discusses the role played by NLRs
      in a variety of inflammatory diseases and describes the remarkable success to
      date of these therapeutic agents in treating some of the disorders associated
      with aberrant NLR function.

PMID- 19090966
TI  - Fibromyalgia and sleep-disordered breathing: the missing link.

PMID- 19090968
TI  - PGRMC1: a new biomarker for the estrogen receptor in breast cancer.
AB  - Estrogen receptor (ER) status is a critical biomarker in breast cancer, in large
      part because the ER is the target of tamoxifen and similar drugs. In the previous
      issue of Breast Cancer Research, Neubauer and colleagues used a proteomic
      approach to identify proteins that are differentially regulated by ER in breast
      tumors. The authors showed that ER-negative tumors have elevated levels of PGRMC1
      (progesterone receptor membrane component-1), a hormone receptor component and
      binding partner for P450 proteins. In contrast, PGRMC1 was phosphorylated in ER
      positive tumors. The staining patterns of ER and PGRMC1 were mutually exclusive
      in breast tumor sections, and PGRMC1 staining was sharply increased in hypoxic
      areas of the tumor. The results suggest that PGRMC1 is a candidate biomarker for
      ER status and hypoxia in breast cancer.

PMID- 19090969
TI  - Putative growth characteristics of micrometastatic breast cancer.
AB  - The fate of cells that disseminate from a primary breast tumour remains poorly
      understood. Studies of the kinetics of recurrence in breast cancer patients are
      raising important questions about the biology of the metastatic process. Where do
      tumour cells reside once they leave the primary tumour, and what factors
      influence their dormancy and recurrent growth? Clinical data analyses are leading
      to hypotheses about the biology of metastasis, dormancy and recurrence. A
      combined clinical and experimental approach to testing these hypotheses will help
      to clarify this important issue in breast cancer biology and patient care.

PMID- 19090971
TI  - Osteopontin: a new role for a familiar actor.
AB  - Our understanding of the events that occur in cancer progression has been
      enhanced by the use of cell lines in vitro. Changes in gene expression, induction
      of signalling, and cell motility can all be investigated in this setting.
      However, other aspects of progression can be revealed only in vivo, especially
      the interactions of tumour cells with host cells and organ systems. In one such
      in vivo model, described by McAllister and colleagues, it proved possible to
      establish a novel function of an already well-characterised protein, osteopontin,
      adding to its attractiveness as a target in cancer therapy.

PMID- 19090970
TI  - Genetic counselling and testing for inherited gene mutations in newly diagnosed
      patients with breast cancer: a review of the existing literature and a proposed
      research agenda.
AB  - Many women newly diagnosed with breast cancer and with a strong family history of
      breast cancer are referred to a family cancer service for genetic counselling and
      for consideration of genetic testing for germline mutations in cancer
      predisposition genes following completion of their cancer treatment. However,
      there is growing evidence that mutation status may influence treatment
      recommendations, and that there may be benefits in having 'treatment-focused
      genetic counselling and testing' available shortly after cancer diagnosis. This
      article reviews the literature that could inform the development of treatment
      focused genetic counselling and testing, including: the rationale for genetic
      testing to aid with treatment decisions; the potential benefits of using mutation
      or risk status to tailor management; the criteria that may be used to identify
      patients most likely to carry germline mutations; and the evidence regarding
      women's decision-making regarding treatment-focused genetic counselling and
      testing and the associated psychological impact.

PMID- 19090972
TI  - A role for prophylactic antibiotics in necrotizing pancreatitis? Why we may never
      know the answer ...
AB  - The use of prophylactic antibiotics in patients with severe acute pancreatitis
      remains an intensely debated topic. Although animal studies consistently
      demonstrated an advantage of antibiotic prophylaxis, the only two blinded
      randomized controlled trials could not confirm these findings. Translation of the
      experimental models in human clinical practice is hampered by a number of
      fundamental differences between experimental pancreatitis and human disease, and
      therefore it is highly unlikely that the pronounced benefit found in experimental
      pancreatitis will ever be demonstrated in human disease. Early and accurate risk
      stratification to identify the patient at risk for infection early in the course
      of the disease seems to be the greatest challenge. Until we are able to
      demonstrate an advantage of antibiotic prophylaxis in a high-risk human
      population, the absence of proven benefit and potential side effects of this
      strategy should be acknowledged and the use of antibiotics should be limited to
      the treatment of documented infection.

PMID- 19090973
TI  - What is a virulence factor?
AB  - Bacterial virulence factors enable a host to replicate and disseminate within a
      host in part by subverting or eluding host defenses. The use of genomic
      techniques has led to the identification of new virulence factors that may serve
      as targets for new therapies. These putative virulence factors must be rigorously
      evaluated with in vitro and in vivo studies with an awareness of the technical
      limitations of each approach as well as an assessment of the prevalence of this
      factor in clinical bacterial isolates retrieved from appropriately controlled
      epidemiologic studies.

PMID- 19090974
TI  - Procalcitonin-guided antibiotics in severe sepsis.

PMID- 19090975
TI  - Computational models in systems biology.
AB  - A report of the 6th International Conference on Computational Methods in Systems
      Biology, Rostock, Germany, 12-15 October 2008.

PMID- 19090976
TI  - Gastrointestinal failure score in critically ill patients.

PMID- 19090978
TI  - Vitamin D or hormone D deficiency in autoimmune rheumatic diseases, including
      undifferentiated connective tissue disease.
AB  - Epidemiological evidence indicates a significant association between vitamin D
      deficiency and an increased incidence of autoimmune diseases. The presence of
      vitamin D receptors in the cells of the immune system and the fact that several
      of these cells produce the vitamin D hormone suggested that vitamin D could have
      immunoregulatory properties, and now potent immuno-modulatory activities on
      dendritic cells, Th1 and Th17 cells, as well as B cells have been confirmed.
      Patients with undifferentiated connective tissue disease also show vitamin D
      deficiency and, interestingly, patients who progress into connective tissue
      diseases have lower vitamin D levels than those who remain in the
      undifferentiated connective tissue disease stage.

PMID- 19090977
TI  - Acute kidney injury on admission to the intensive care unit: where to go from
      here?
AB  - Acute kidney injury (AKI) is a common problem, especially in critically ill
      patients. In Critical Care, Kolhe and colleagues report that 6.3% of 276,731
      patients in 170 intensive care units (ICUs) in the UK had evidence of severe AKI
      within the first 24 hours of admission to ICU. ICU and hospital mortality as well
      as length of stay in hospital were significantly increased. In light of this
      serious burden on individuals and the health system in general, the following
      commentary discusses the current state of knowledge of AKI in ICU and calls for
      more attention to preventive strategies.

PMID- 19090979
TI  - Neuronal remodeling on the evolutionary timescale.
AB  - Despite its remarkable capacity to undergo change at timescales ranging from a
      fraction of a second to a lifetime, there are many aspects of the nervous system
      that can be modified only at the enormously longer evolutionary timescale. A new
      study in BMC Biology using nematodes illustrates such evolutionary neuronal
      remodeling.

PMID- 19090980
TI  - The future of artemisinins: natural, synthetic or recombinant?
AB  - Artemisinins are the most important anti-malarial drugs in use today, but are
      more costly than previous anti-malarials and production and price tend to
      fluctuate. Alternative ways of producing artemisinins are discussed here in the
      light of a recent paper in BMC Biotechnology on improving the yield of the
      precursor, artemisinic acid, in genetically engineered yeast.

PMID- 19090981
TI  - Antiphospholipid syndrome.
AB  - Antiphospholipid syndrome is diagnosed when arterial or venous thrombosis or
      recurrent miscarriages occur in a person in whom laboratory tests for
      antiphospholipid antibodies (anticardiolipin antibodies and/or lupus
      anticoagulant and/or anti-beta 2-glycoprotein I) are positive. Despite the strong
      association between antiphospho-lipid antibodies and thrombosis, their pathogenic
      role in the development of thrombosis has not been fully elucidated. Novel
      mechanisms involving both the complement pathway and micro-particles have been
      described. The knowledge of these new pathogenic approaches might identify novel
      therapeutic targets and therefore may improve the management of these patients.

PMID- 19090982
TI  - Small molecule activators of the Trk receptors for neuroprotection.
AB  - The neurotrophin signaling network is critical to the development and survival of
      many neuronal populations. Especially sensitive to imbalances in the neurotrophin
      system, cholinergic neurons in the basal forebrain are progressively lost in
      Alzheimer's disease. Therapeutic use of neurotrophins to prevent this loss is
      hampered, however, by a number of pharmacological challenges. These include a
      lack of transport across the blood-brain barrier, rapid degradation in the
      circulation, and difficulty in production. In this review we discuss the evidence
      supporting the neurotrophin system's role in preventing neurodegeneration and
      survey some of the pharmacological strategies being pursued to develop effective
      therapeutics targeting neurotrophin function.

PMID- 19090983
TI  - Alternative splicing of exon 10 in the tau gene as a target for treatment of
      tauopathies.
AB  - Tau aggregation is one of the major features in Alzheimer's disease and in
      several other tauopathies, including frontotemporal dementia with Parkinsonism
      linked to chromosome 17 (FTDP-17), and progressive supranuclear palsy (PSP). More
      than 35 mutations in the tau gene have been identified from FTDP-17 patients. A
      group of these mutations alters splicing of exon 10, resulting in an increase in
      exon 10 inclusion into tau mRNA. Abnormal splicing with inclusion of exon 10 into
      tau mRNA has also been observed in PSP and AD patients. These results indicate
      that abnormal splicing of exon 10, leading to the production of tau with exon 10,
      is probably one of the mechanisms by which tau accumulates and aggregates in
      tauopathic brains. Therefore, modulation of exon 10 splicing in the tau gene
      could potentially be targeted to prevent tauopathies. To identify small molecules
      or compounds that could potentially be developed into drugs to treat tauopathies,
      we established a cell-based high-throughput screening assay. In this review, we
      will discuss how realistic, specific biological molecules can be found to
      regulate exon 10 splicing in the tau gene for potential treatment of tauopathies.

PMID- 19090984
TI  - Allopregnanolone-induced rise in intracellular calcium in embryonic hippocampal
      neurons parallels their proliferative potential.
AB  - BACKGROUND: Factors that regulate intracellular calcium concentration are known
      to play a critical role in brain function and neural development, including
      neural plasticity and neurogenesis. We previously demonstrated that the
      neurosteroid allopregnanolone (APalpha; 5alpha-pregnan-3alpha-ol-20-one) promotes
      neural progenitor proliferation in vitro in cultures of rodent hippocampal and
      human cortical neural progenitors, and in vivo in triple transgenic Alzheimer's
      disease mice dentate gyrus. We also found that APalpha-induced proliferation of
      neural progenitors is abolished by a calcium channel blocker, nifedipine,
      indicating a calcium dependent mechanism for the proliferation. METHODS: In the
      present study, we investigated the effect of APalpha on the regulation of
      intracellular calcium concentration in E18 rat hippocampal neurons using
      ratiometric Fura2-AM imaging. RESULTS: Results indicate that APalpha rapidly
      increased intracellular calcium concentration in a dose-dependent and
      developmentally regulated manner, with an EC50 of 110 +/- 15 nM and a maximal
      response occurring at three days in vitro. The stereoisomers 3beta-hydroxy-5alpha
      hydroxy-pregnan-20-one, and 3beta-hydroxy-5beta-hydroxy-pregnan-20-one, as well
      as progesterone, were without significant effect. APalpha-induced intracellular
      calcium concentration increase was not observed in calcium depleted medium and
      was blocked in the presence of the broad spectrum calcium channel blocker La3+,
      or the L-type calcium channel blocker nifedipine. Furthermore, the GABAA receptor
      blockers bicuculline and picrotoxin abolished APalpha-induced intracellular
      calcium concentration rise. CONCLUSION: Collectively, these data indicate that
      APalpha promotes a rapid, dose-dependent, stereo-specific, and developmentally
      regulated increase of intracellular calcium concentration in rat embryonic
      hippocampal neurons via a mechanism that requires both the GABAA receptor and L
      type calcium channel. These data suggest that APalpha-induced intracellular
      calcium concentration increase serves as the initiation mechanism whereby APalpha
      promotes neurogenesis.

PMID- 19090985
TI  - The p38alpha mitogen-activated protein kinase as a central nervous system drug
      discovery target.
AB  - Protein kinases are critical modulators of a variety of cellular signal
      transduction pathways, and abnormal phosphorylation events can be a cause or
      contributor to disease progression in a variety of disorders. This has led to the
      emergence of protein kinases as an important new class of drug targets for small
      molecule therapeutics. A serine/threonine protein kinase, p38alpha mitogen
      activated protein kinase (MAPK), is an established therapeutic target for
      peripheral inflammatory disorders because of its critical role in regulation of
      proinflammatory cytokine production. There is increasing evidence that p38alpha
      MAPK is also an important regulator of proinflammatory cytokine levels in the
      central nervous system, raising the possibility that the kinase may be a drug
      discovery target for central nervous system disorders where cytokine
      overproduction contributes to disease progression. Development of bioavailable,
      central nervous system-penetrant p38alpha MAPK inhibitors provides the required
      foundation for drug discovery campaigns targeting p38alpha MAPK in
      neurodegenerative disorders.

PMID- 19090986
TI  - Immune defects in Alzheimer's disease: new medications development.
AB  - Alzheimer's disease (AD) is a neurodegenerative disease characterized by the
      accumulation of intracellular and extracellular aggregates. According to the
      amyloid beta (Abeta) hypothesis, amyloidosis occurring in the brain is a leading
      cause of neurodegeneration in AD. Defects in the innate immune system may
      decrease the clearance of Abeta in the brain. Macrophages of most AD patients do
      not transport Abeta into endosomes and lysosomes, and monocytes from AD patients
      do not efficiently clear Abeta from AD brain. After stimulation with Abeta,
      mononuclear cells of normal subjects display up-regulated transcription of MGAT3,
      which encodes beta-1,4-mannosyl-glycoprotein 4-beta-N
      acetylglucosaminyltransferase, and Toll-like receptor (TLR) genes. Monocytes of
      AD patients generally down-regulate these genes. A commonly used, naturally
      occurring material from a spice that enhances certain key functions defective in
      cells of innate immunity of many AD patients has shown epidemiologic rationale
      for use in AD treatment. Bisdemethoxycurcumin, a natural curcumin, is a minor
      constituent of turmeric (curry), and it enhances phagocytosis and clearance of
      Abeta in cells from most AD patients. We confirmed the effectiveness of a
      synthetic version of the same compound. In mononuclear cells of most AD patients,
      bisdemethoxycurcumin enhanced defective phagocytosis of Abeta and increased the
      transcription of MGAT3 and TLR genes. The potency of bisdemethoxycurcumin as a
      highly purified compound in facilitating the clearance of Abeta in mononuclear
      cells suggests the promise of enhanced effectiveness compared to curcuminoid
      mixtures. Bisdemethoxycurcumin appears to enhance immune function in mononuclear
      cells of AD patients and may provide a novel approach to AD immunotherapy.

PMID- 19090987
TI  - Development of cognitive enhancers based on inhibition of insulin-regulated
      aminopeptidase.
AB  - The peptides angiotensin IV and LVV-hemorphin 7 were found to enhance memory in a
      number of memory tasks and reverse the performance deficits in animals with
      experimentally induced memory loss. These peptides bound specifically to the
      enzyme insulin-regulated aminopeptidase (IRAP), which is proposed to be the site
      in the brain that mediates the memory effects of these peptides. However, the
      mechanism of action is still unknown but may involve inhibition of the
      aminopeptidase activity of IRAP, since both angiotensin IV and LVV-hemorphin 7
      are competitive inhibitors of the enzyme. IRAP also has another functional domain
      that is thought to regulate the trafficking of the insulin-responsive glucose
      transporter GLUT4, thereby influencing glucose uptake into cells. Although the
      exact mechanism by which the peptides enhance memory is yet to be elucidated,
      IRAP still represents a promising target for the development of a new class of
      cognitive enhancing agents.

PMID- 19090988
TI  - Cognitive-enhancing effects of angiotensin IV.
AB  - Angiotensin IV is a derivative of the potent vasoconstrictor angiotensin II and
      it has been shown to enhance acquisition, consolidation and recall in animal
      models of learning and memory when administered centrally or peripherally.
      Whether changes in angiotensin IV activity underlie the cognitive effects of
      those cardiovascular drugs designed to disrupt the peripheral renin-angiotensin
      system in humans remains undetermined, but angiotensin IV appears to be a worthy
      candidate for consideration in drug development programmes. The mechanism of
      action of angiotensin IV is still debated, although its AT4 receptor has been
      convincingly identified as being insulin-regulated amino peptidase, which is also
      known as oxytocinase and placental leucine aminopeptidase. It is speculated that
      angiotensin IV may interact with insulin-regulated amino peptidase to enhance
      neuronal glucose uptake, prevent metabolism of other neuroactive peptides, induce
      changes in extracellular matrix molecules, or induce release of acetylcholine
      and/or dopamine. All of these things may be responsible for the beneficial
      effects on cognition, but none of them are yet proven. Importantly, strain
      differences in murine responses to angiotensin IV suggest that some individuals
      may benefit from drugs targeted to the AT4 receptor whilst others may be
      refractory. At present it thus appears that those individuals with the poorest
      baseline cognition may receive greatest benefit, but possible genetic differences
      in responses to angiotensin IV cannot be ruled-out.

PMID- 19090989
TI  - Hypometabolism as a therapeutic target in Alzheimer's disease.
AB  - The pathology of Alzheimer's disease (AD) is characterized by cerebral atrophy in
      frontal, temporal, and parietal regions, with senile plaques, dystrophic
      neurites, and neurofibrillar tangles within defined areas of the brain. Another
      characteristic of AD is regional hypometabolism in the brain. This decline in
      cerebral glucose metabolism occurs before pathology and symptoms manifest,
      continues as symptoms progress, and is more severe than that of normal aging.
      Ketone bodies are an efficient alternative fuel for cells that are unable to
      metabolize glucose or are 'starved' of glucose. AC-1202 is designed to elevate
      serum ketone levels safely. We previously showed that treatment with AC-1202 in
      patients with mild-to-moderate AD improves memory and cognition. Treatment
      outcomes were influenced by apolipoprotein E genotype status. These data suggest
      that AC-1202 may be an effective treatment for cognitive dysfunction by providing
      an alternative substrate for use by glucose-compromised neurons.

PMID- 19090990
TI  - Physiological and pathological aspects of Abeta in iron homeostasis via 5'UTR in
      the APP mRNA and the therapeutic use of iron-chelators.
AB  - Many studies have highlighted the pathological involvement of iron accumulation
      and iron-related oxidative stress (OS) in Alzheimer's disease (AD). Iron was
      further demonstrated to modulate expression of the Alzheimer's amyloid precursor
      holo-protein (APP) by a mechanism similar to that of regulation of ferritin-L and
      -H mRNA translation through an iron-responsive element (IRE) in their 5'
      untranslated regions (UTRs). Here, we discuss two aspects of the link between
      iron and AD, in relation to the recently discovered IRE in the 5'UTR of APP mRNA.
      The first is the physiological aspect: a compensatory neuroprotective response of
      amyloid-beta protein (Abeta) in reducing iron-induced neurotoxicity. Thus, given
      that Abeta possesses iron chelation sites, it is hypothesized that OS-induced
      intracellular iron may stimulate APP holo-protein translation (via the APP 5'UTR)
      and subsequently the generation of its cleavage product, Abeta, as a compensatory
      response that eventually reduces OS. The second is the pathological aspect: iron
      chelating compounds target the APP 5'UTR and possess the capacity to reduce APP
      translation, and subsequently Abeta levels, and thus represent molecules with
      high potential in the development of drugs for the treatment of AD.

PMID- 19090991
TI  - The potential of hematopoietic growth factors for treatment of Alzheimer's
      disease: a mini-review.
AB  - There are no effective interventions that significantly forestall or reverse
      neurodegeneration and cognitive decline in Alzheimer's disease. In the past
      decade, the generation of new neurons has been recognized to continue throughout
      adult life in the brain's neurogenic zones. A major challenge has been to find
      ways to harness the potential of the brain's own neural stem cells to repair or
      replace injured and dying neurons. The administration of hematopoietic growth
      factors or cytokines has been shown to promote brain repair by a number of
      mechanisms, including increased neurogenesis, anti-apoptosis and increased
      mobilization of bone marrow-derived microglia into brain. In this light, cytokine
      treatments may provide a new therapeutic approach for many brain disorders,
      including neurodegenerative diseases like Alzheimer's disease. In addition,
      neuronal hematopoietic growth factor receptors provide novel targets for the
      discovery of peptide-mimetic drugs that can forestall or reverse the pathological
      progression of Alzheimer's disease.

PMID- 19090992
TI  - Selective amyloid-beta lowering agents.
AB  - The amyloid-beta peptide (Abeta), implicated in the pathogenesis of Alzheimer's
      disease (AD), is produced through sequential proteolysis of the Abeta precursor
      protein (APP) by beta- and gamma-secretases. Thus, blocking either of these two
      proteases, directly or indirectly, is potentially worthwhile toward developing AD
      therapeutics. beta-Secretase is a membrane-tethered pepsin-like aspartyl protease
      suitable for structure-based design, whereas gamma-secretase is an unusual,
      heterotetrameric membrane-embedded aspartyl protease. While gamma-secretase
      inhibitors entered clinical trials first due to their superior pharmacological
      properties (for example, brain penetration) over beta-secretase inhibitors, it
      has since become clear that gamma-secretase inhibitors can cause mechanism-based
      toxicities owing to interference with the proteolysis of another gamma-secretase
      substrate, the Notch receptor. Strategies for targeting Abeta production at the
      gamma-secretase level without blocking Notch signalling will be discussed. Other
      strategies utilizing cell-based screening have led to the identification of novel
      Abeta lowering agents that likewise leave Notch proteolysis intact. The mechanism
      by which these agents lower Abeta is unknown, but these compounds may ultimately
      reveal new targets for AD therapeutics.

PMID- 19090993
TI  - Preventing beta-amyloid fibrillization and deposition: beta-sheet breakers and
      pathological chaperone inhibitors.
AB  - Central to the pathogenesis of Alzheimer's disease (AD) is the conversion of
      normal, soluble beta-amyloid (sAbeta) to oligomeric, fibrillar Abeta. This
      process of conformational conversion can be influenced by interactions with other
      proteins that can stabilize the disease-associated state; these proteins have
      been termed 'pathological chaperones'. In a number of AD models, intervention
      that block soluble Abeta aggregation, including beta-sheet breakers, and
      compounds that block interactions with pathological chaperones, have been shown
      to be highly effective. When combined with early pathology detection, these
      therapeutic strategies hold great promise as effective and relatively toxicity
      free methods of preventing AD related pathology.

PMID- 19090994
TI  - Therapeutic potential of resveratrol in Alzheimer's disease.
AB  - Several epidemiological studies indicate that moderate consumption of red wine is
      associated with a lower incidence of dementia and Alzheimer's disease. Red wine
      is enriched in antioxidant polyphenols with potential neuroprotective activities.
      Despite scepticism concerning the bioavailability of these polyphenols, in vivo
      data have clearly demonstrated the neuroprotective properties of the naturally
      occurring polyphenol resveratrol in rodent models for stress and diseases.
      Furthermore, recent work in cell cultures and animal models has shed light on the
      molecular mechanisms potentially involved in the beneficial effects of
      resveratrol intake against the neurodegenerative process in Alzheimer's disease.

PMID- 19090995
TI  - Heat shock protein 90: translation from cancer to Alzheimer's disease treatment?
AB  - Both malignant transformation and neurodegeneration, as it occurs in Alzheimer's
      disease, are complex and lengthy multistep processes characterized by abnormal
      expression, post-translational modification, and processing of certain proteins.
      To maintain and allow the accumulation of these dysregulated processes, and to
      facilitate the step-wise evolution of the disease phenotype, cells must co-opt a
      compensatory regulatory mechanism. In cancer, this role has been attributed to
      heat shock protein 90 (Hsp90), a molecular chaperone that maintains the
      functional conformation of multiple proteins involved in cell-specific oncogenic
      processes. In this sense, at the phenotypic level, Hsp90 appears to serve as a
      biochemical buffer for the numerous cancer-specific lesions that are
      characteristic of diverse tumors. The current review proposes a similar role for
      Hsp90 in neurodegeneration. It will present experimentally demonstrated, but also
      hypothetical, roles that suggest Hsp90 can act as a regulator of pathogenic
      changes that lead to the neurodegenerative phenotype in Alzheimer's disease.

PMID- 19090997
TI  - Structure and regulation of MARK, a kinase involved in abnormal phosphorylation
      of Tau protein.
AB  - Protein kinases of the MARK family phosphorylate tau protein in its repeat domain
      and thereby regulate its affinity for microtubules and affect the aggregation of
      tau into Alzheimer paired helical filaments. We are searching for low molecular
      weight compounds to interfere with the activity of MARK and its pathways. Here we
      summarize structural features of MARK and cellular pathways of regulation.

PMID- 19090998
TI  - Risk in CNS drug discovery: focus on treatment of Alzheimer's disease.
AB  - Despite rapid progress in our understanding of disease mechanisms and an
      exploding list of new targets for therapeutic intervention, drug discovery and
      development remains a highly risky business. Understanding the risk involved
      requires appreciation of the differing perspectives of risk held by the various
      stakeholders involved in drug research. Risk can be reduced by thoughtful
      management of drug candidate selection, careful planning and program execution by
      a team of engaged experts, and disciplined decision making. Drug development is
      particularly challenging for treatments of neurodegenerative diseases such as
      Alzheimer's disease, in which translation from animal models of efficacy to human
      success is poor or unknown, the timelines for clinical study are long, and the
      markers of efficacy are still evolving. Despite this there are several therapies
      in clinical development that hold the promise of influencing this disease through
      novel and possibly synergistic mechanisms.

PMID- 19090996
TI  - NADPH oxidase as a therapeutic target in Alzheimer's disease.
AB  - At present, available treatments for Alzheimer's disease (AD) are largely unable
      to halt disease progression. Microglia, the resident macrophages in the brain,
      are strongly implicated in the pathology and progressively degenerative nature of
      AD. Specifically, microglia are activated in response to both beta amyloid
      (Abeta) and neuronal damage, and can become a chronic source of neurotoxic
      cytokines and reactive oxygen species (ROS). NADPH oxidase is a multi-subunit
      enzyme complex responsible for the production of both extracellular and
      intracellular ROS by microglia. Importantly, NADPH oxidase expression is
      upregulated in AD and is an essential component of microglia-mediated Abeta
      neurotoxicity. Activation of microglial NADPH oxidase causes neurotoxicity
      through two mechanisms: 1) extracellular ROS produced by microglia are directly
      toxic to neurons; 2) intracellular ROS function as a signaling mechanism in
      microglia to amplify the production of several pro-inflammatory and neurotoxic
      cytokines (for example, tumor necrosis factor-alpha, prostaglandin E2, and
      interleukin-1beta). The following review describes how targeting NADPH oxidase
      can reduce a broad spectrum of toxic factors (for example, cytokines, ROS, and
      reactive nitrogen species) to result in inhibition of neuronal damage from two
      triggers of deleterious microglial activation (Abeta and neuron damage), offering
      hope in halting the progression of AD.

PMID- 19090999
TI  - Developing drugs that can cross the blood-brain barrier: applications to
      Alzheimer's disease.
AB  - Development of therapeutics for the central nervous system is one of the most
      challenging areas in drug development. This is primarily because, in addition to
      all of the other complications one faces in developing new drugs targeting
      peripheral sites, one must also negotiate the blood-brain barrier (BBB). There
      are dozens of strategies to overcome the obstacle of the BBB, but many of these
      are bound to fail, barring extreme serendipity, because they are based on an
      inaccurate or incomplete picture of the BBB. This article therefore starts with a
      brief review of the BBB as it pertains to drug development. It then examines some
      examples of the delivery of drugs to the central nervous system that are relevant
      to Alzheimer's disease, placing emphasis on peptides, antibodies, and antisense
      oligonucleotides.

PMID- 19091000
TI  - NAP and D-SAL: neuroprotection against the beta amyloid peptide (1-42).
AB  - INTRODUCTION: NAP (Asn-Ala-Pro-Val-Ser-Ile-Pro-Gln, single amino acid letter
      code, NAPVSIPQ), an eight amino acid neuroprotective peptide derived from
      activity-dependent neuroprotective protein (ADNP), exhibits some structural
      similarity to activity-dependent neurotropic factor-9 (ADNF-9; Ser-Alal-Leu-Leu
      Arg-Ser-Ile-Pro-Ala, SALLRSIPA). Both peptides are also active in the all D-amino
      acid conformation, termed D-NAP and D-SAL. Original results utilizing affinity
      chromatography coupled to mass spectrometry identified tubulin, the subunit
      protein of microtubules, as the major NAP-associating protein in brain. The NAP
      tubulin association was found to be diminished in the presence of ADNF-9, D-NAP,
      and D-SAL, suggesting a common target of neuroprotection. The beta amyloid
      peptide interacts with microtubules, and previous studies have demonstrated
      protection against beta amyloid (25-35) toxicity by NAP and ADNF-9. NAP also
      inhibits beta amyloid (25-35 and 1-40) aggregation. METHODS: Cerebral cortical
      cultures derived from newborn rats were used in neuronal survival assays to test
      the activity of both NAP and D-SAL against the major Alzheimer's disease toxic
      peptide beta amyloid (1-42). RESULTS: NAP and D-SAL protected cerebral cortical
      neurons against the major Alzheimer's disease toxic peptide beta amyloid (1-42).
      Maximal protection of both peptides was observed at concentrations of 10-15 to 10
      10 mol/l. CONCLUSION: These findings, together with those of previous in vivo
      studies conducted in relevant Alzheimer's disease models, pave the path to drug
      development. Bioavailability studies indicated that NAP penetrates cells and
      crosses the blood-brain barrier after nasal or systemic administration. Phase II
      clinical trials of NAP are currently in progress by Allon Therapeutics Inc.

PMID- 19091001
TI  - Nanotechnology approaches to crossing the blood-brain barrier and drug delivery
      to the CNS.
AB  - Nanotechnologies are materials and devices that have a functional organization in
      at least one dimension on the nanometer (one billionth of a meter) scale, ranging
      from a few to about 100 nanometers. Nanoengineered materials and devices aimed at
      biologic applications and medicine in general, and neuroscience in particular,
      are designed fundamentally to interface and interact with cells and their tissues
      at the molecular level. One particularly important area of nanotechnology
      application to the central nervous system (CNS) is the development of
      technologies and approaches for delivering drugs and other small molecules such
      as genes, oligonucleotides, and contrast agents across the blood brain barrier
      (BBB). The BBB protects and isolates CNS structures (i.e. the brain and spinal
      cord) from the rest of the body, and creates a unique biochemical and
      immunological environment. Clinically, there are a number of scenarios where
      drugs or other small molecules need to gain access to the CNS following systemic
      administration, which necessitates being able to cross the BBB. Nanotechnologies
      can potentially be designed to carry out multiple specific functions at once or
      in a predefined sequence, an important requirement for the clinically successful
      delivery and use of drugs and other molecules to the CNS, and as such have a
      unique advantage over other complimentary technologies and methods. This brief
      review introduces emerging work in this area and summarizes a number of example
      applications to CNS cancers, gene therapy, and analgesia.

PMID- 19091002
TI  - Intranasal delivery bypasses the blood-brain barrier to target therapeutic agents
      to the central nervous system and treat neurodegenerative disease.
AB  - Intranasal delivery provides a practical, non-invasive method of bypassing the
      blood-brain barrier (BBB) to deliver therapeutic agents to the brain and spinal
      cord. This technology allows drugs that do not cross the BBB to be delivered to
      the central nervous system within minutes. It also directly delivers drugs that
      do cross the BBB to the brain, eliminating the need for systemic administration
      and its potential side effects. This is possible because of the unique
      connections that the olfactory and trigeminal nerves provide between the brain
      and external environment. Intranasal delivery does not necessarily require any
      modification to therapeutic agents. A wide variety of therapeutics, including
      both small molecules and macromolecules, can be targeted to the olfactory system
      and connected memory areas affected by Alzheimer's disease. Using the intranasal
      delivery system, researchers have reversed neurodegeneration and rescued memory
      in a transgenic mouse model of Alzheimer's disease. Intranasal insulin-like
      growth factor-I, deferoxamine, and erythropoietin have been shown to protect the
      brain against stroke in animal models. Intranasal delivery has been used to
      target the neuroprotective peptide NAP to the brain to treat neurodegeneration.
      Intranasal fibroblast growth factor-2 and epidermal growth factor have been shown
      to stimulate neurogenesis in adult animals. Intranasal insulin improves memory,
      attention, and functioning in patients with Alzheimer's disease or mild cognitive
      impairment, and even improves memory and mood in normal adult humans. This new
      method of delivery can revolutionize the treatment of Alzheimer's disease,
      stroke, and other brain disorders.

PMID- 19091003
TI  - Intranasal administration of acetylcholinesterase inhibitors.
AB  - This short review outlines the rationale, challenges, and opportunities for
      intranasal acetylcholinesterases, in particular galantamine. An in vitro
      screening model facilitated the development of a therapeutically viable
      formulation. In vivo testing confirmed achievement of therapeutically relevant
      drug levels that matched or exceeded those for oral dosing, with a dramatic
      reduction in undesired emetic responses. Intranasal drug delivery is an effective
      option for the treatment of Alzheimer's disease and other central nervous system
      disorders.

PMID- 19091004
TI  - Requirements for a lead compound to become a clinical candidate.
AB  - A drug candidate suitable for clinical testing is expected to bind selectively to
      the receptor site on the target, to elicit the desired functional response of the
      target molecule, and to have adequate bioavailability and biodistribution to
      elicit the desired responses in animals and humans; it must also pass formal
      toxicity evaluation in animals. The path from lead to clinical drug candidate
      represents the most idiosyncratic segment of drug discovery and development. Each
      program is unique and setbacks are common, making it difficult to predict
      accurately the duration or costs of this segment. Because of incidents of
      unpredicted human toxicity seen in recent years, the regulatory agencies and
      public demands for safety of new drug candidates have become very strict, and
      safety issues are dominant when identifying a clinical drug candidate.

PMID- 19091005
TI  - Micrometastatic spread in breast cancer: detection, molecular characterization
      and clinical relevance.
AB  - Immunocytochemical or molecular assays allow the detection of single disseminated
      tumor cells (DTCs) in the bone marrow (BM) or the peripheral blood in 10% to 60%
      of breast cancer patients without signs of metastasis. Results from recently
      reported studies suggest that circulating tumor cell (CTC) levels may serve as a
      prognostic marker and be used for early assessment of therapeutic response in
      patients with metastatic breast cancer. In early stage breast cancer, however,
      the impact of CTCs is less well established than that of DTCs in BM, where
      several clinical studies demonstrated that such cells are an independent
      prognostic factor at primary diagnosis. The characterization of DTCs/CTCs has
      already shed new light on the complex process underlying early tumor cell
      dissemination and metastatic progression in cancer patients. Characterization of
      DTCs should help to identify novel targets for biological therapies aimed to
      prevent metastatic relapse. In addition, understanding tumor 'dormancy' and
      identifying metastatic stem cells might result in the development of new
      therapeutic concepts.

PMID- 19091006
TI  - Mechanisms of metastasis.
AB  - Metastasis is an enormously complex process that remains to be a major problem in
      the management of cancer. The fact that cancer patients might develop metastasis
      after years or even decades from diagnosis of the primary tumor makes the
      metastatic process even more complex. Over the years many hypotheses were
      developed to try to explain the inefficiency of the metastatic process, but none
      of these theories completely explains the current biological and clinical
      observations. In this review we summarize some of the proposed models that were
      developed in attempt to understand the mechanisms of tumor dissemination and
      colonization as well as metastatic progression.

PMID- 19091008
TI  - Emerging strengths in Asia Pacific bioinformatics.
AB  - The 2008 annual conference of the Asia Pacific Bioinformatics Network (APBioNet),
      Asia's oldest bioinformatics organisation set up in 1998, was organized as the
      7th International Conference on Bioinformatics (InCoB), jointly with the
      Bioinformatics and Systems Biology in Taiwan (BIT 2008) Conference, Oct. 20-23,
      2008 at Taipei, Taiwan. Besides bringing together scientists from the field of
      bioinformatics in this region, InCoB is actively involving researchers from the
      area of systems biology, to facilitate greater synergy between these two groups.
      Marking the 10th Anniversary of APBioNet, this InCoB 2008 meeting followed on
      from a series of successful annual events in Bangkok (Thailand), Penang
      (Malaysia), Auckland (New Zealand), Busan (South Korea), New Delhi (India) and
      Hong Kong. Additionally, tutorials and the Workshop on Education in
      Bioinformatics and Computational Biology (WEBCB) immediately prior to the 20th
      Federation of Asian and Oceanian Biochemists and Molecular Biologists (FAOBMB)
      Taipei Conference provided ample opportunity for inducting mainstream biochemists
      and molecular biologists from the region into a greater level of awareness of the
      importance of bioinformatics in their craft. In this editorial, we provide a
      brief overview of the peer-reviewed manuscripts accepted for publication herein,
      grouped into thematic areas. As the regional research expertise in bioinformatics
      matures, the papers fall into thematic areas, illustrating the specific
      contributions made by APBioNet to global bioinformatics efforts.

PMID- 19091007
TI  - Molecular imaging as a tool for translating breast cancer science.
AB  - The ability to measure biochemical and molecular processes underlies progress in
      breast cancer biology and treatment. These assays have traditionally been
      performed by analysis of cell culture or tissue samples. More recently,
      functional and molecular imaging has allowed the in vivo assay of biochemistry
      and molecular biology, which is highly complementary to tissue-based assays. This
      review briefly describes different imaging modalities used in molecular imaging
      and then reviews applications of molecular imaging to breast cancer, with a focus
      on translational work. It includes sections describing work in functional and
      physiological tumor imaging, imaging gene product expression, imaging the tumor
      microenvironment, reporter gene imaging, and cell labeling. Work in both animal
      models and human is discussed with an eye towards studies that have relevance to
      breast cancer treatment in patients.

PMID- 19091009
TI  - Functional analysis of novel SNPs and mutations in human and mouse genomes.
AB  - BACKGROUND: With the flood of information generated by the new generation of
      sequencing technologies, more efficient bioinformatics tools are needed for in
      depth impact analysis of novel genomic variations. FANS (Functional Analysis of
      Novel SNPs) was developed to streamline comprehensive but tedious functional
      analysis steps into a few clicks and to offer a carefully designed presentation
      of results so researchers can focus more on thinking instead of typing and
      calculating. RESULTS: FANS http://fans.ngc.sinica.edu.tw/ harnesses the power of
      public information databases and powerful tools from six well established
      websites to enhance the efficiency of analysis of novel variations. FANS can
      process any point change in any coding region or GT-AG splice site to provide a
      clear picture of the disease risk of a prioritized variation by classifying
      splicing and functional alterations into one of nine risk subtypes with five risk
      levels. CONCLUSION: FANS significantly simplifies the analysis operations to a
      four-step procedure while still covering all major areas of interest to
      researchers. FANS offers a convenient way to prioritize the variations and select
      the ones with most functional impact for validation. Additionally, the program
      offers a distinct improvement in efficiency over manual operations in our
      benchmark test.

PMID- 19091010
TI  - Ortholog-based protein-protein interaction prediction and its application to
      inter-species interactions.
AB  - BACKGROUND: The rapid growth of protein-protein interaction (PPI) data has led to
      the emergence of PPI network analysis. Despite advances in high-throughput
      techniques, the interactomes of several model organisms are still far from
      complete. Therefore, it is desirable to expand these interactomes with ortholog
      based and other methods. RESULTS: Orthologous pairs of 18 eukaryotic species were
      expanded and merged with experimental PPI datasets. The contributions of
      interologs from each species were evaluated. The expanded orthologous pairs
      enable the inference of interologs for various species. For example, more than
      32,000 human interactions can be predicted. The same dataset has also been
      applied to the prediction of host-pathogen interactions. PPIs between P.
      falciparum calmodulin and several H. sapiens proteins are predicted, and these
      interactions may contribute to the maintenance of host cell Ca2+ concentration.
      Using comparisons with Bayesian and structure-based approaches, interactions
      between putative HSP40 homologs of P. falciparum and the H. sapiens TNF receptor
      associated factor family are revealed, suggesting a role for these interactions
      in the interference of the human immune response to P. falciparum. CONCLUSION:
      The PPI datasets are available from POINT http://point.bioinformatics.tw/ and
      POINeT http://poinet.bioinformatics.tw/. Further development of methods to
      predict host-pathogen interactions should incorporate multiple approaches in
      order to improve sensitivity, and should facilitate the identification of targets
      for drug discovery and design.

PMID- 19091011
TI  - Real value prediction of protein solvent accessibility using enhanced PSSM
      features.
AB  - BACKGROUND: Prediction of protein solvent accessibility, also called accessible
      surface area (ASA) prediction, is an important step for tertiary structure
      prediction directly from one-dimensional sequences. Traditionally, predicting
      solvent accessibility is regarded as either a two- (exposed or buried) or three
      state (exposed, intermediate or buried) classification problem. However, the
      states of solvent accessibility are not well-defined in real protein structures.
      Thus, a number of methods have been developed to directly predict the real value
      ASA based on evolutionary information such as position specific scoring matrix
      (PSSM). RESULTS: This study enhances the PSSM-based features for real value ASA
      prediction by considering the physicochemical properties and solvent propensities
      of amino acid types. We propose a systematic method for identifying residue
      groups with respect to protein solvent accessibility. The amino acid columns in
      the PSSM profile that belong to a certain residue group are merged to generate
      novel features. Finally, support vector regression (SVR) is adopted to construct
      a real value ASA predictor. Experimental results demonstrate that the features
      produced by the proposed selection process are informative for ASA prediction.
      CONCLUSION: Experimental results based on a widely used benchmark reveal that the
      proposed method performs best among several of existing packages for performing
      ASA prediction. Furthermore, the feature selection mechanism incorporated in this
      study can be applied to other regression problems using the PSSM. The program and
      data are available from the authors upon request.

PMID- 19091012
TI  - WSPMaker: a web tool for calculating selection pressure in proteins and domains
      using window-sliding.
AB  - BACKGROUND: In the study of adaptive evolution, it is important to detect the
      protein coding sites where natural selection is acting. In general, the ratio of
      the rate of non-synonymous substitutions (Ka) to the rate of synonymous
      substitutions (Ks) is used to estimate either negative or positive selection for
      an entire gene region of interest. However, since each amino acid in a region has
      a different function and structure, the type and strength of natural selection
      may be different for each amino acid. Specifically, domain sites on the protein
      are indicative of structurally and functionally important sites. Therefore,
      Window-sliding tools can be used to detect evolutionary forces acting on mutation
      sites. RESULTS: This paper reports the development of a web-based tool, WSPMaker
      (Window-sliding Selection pressure Plot Maker), for calculating selection
      pressures (estimated by Ka/Ks) in the sub-regions of two protein-coding DNA
      sequences (CDSs). The program uses a sliding window on DNA with a user-defined
      window length. This enables the investigation of adaptive protein evolution and
      shows selective constraints of the overall/specific region(s) of two orthologous
      gene-coding DNA sequences. The method accommodates various evolutionary models
      and options such as the sliding window size. WSPmaker uses domain information
      from Pfam HMM models to detect highly conserved residues within orthologous
      proteins. CONCLUSION: WSPMaker is a web tool for scanning and calculating
      selection pressures (estimated by Ka/Ks) in sub-regions of two protein-coding DNA
      sequences (CDSs).

PMID- 19091013
TI  - Molecular docking studies of dithionitrobenzoic acid and its related compounds to
      protein disulfide isomerase: computational screening of inhibitors to HIV-1
      entry.
AB  - BACKGROUND: Entry of HIV-1 into human lymphoid requires activities of viral
      envelope glycoproteins gp120 and gp41, and two host-cell proteins, the primary
      receptor CD4 and a chemokine co-receptor. In addition, a third cell-surface
      protein called protein disulfide isomerase (PDI) is found to play a major role in
      HIV-1 entry. PDI is capable of mediating thio-disulfide interchange reactions and
      could enable the reduction of gp120 disulfide bonds, which triggers the major
      conformational changes in gp120 and gp41 required for virus entry. In this
      scenario, inhibition of HIV-1 entry can be brought about by introducing agents
      that can block thiol-disulfide interchange reaction of cell surface PDI. There
      have been studies with agents that inhibit PDI activity, but the exact mode of
      binding remains to be elucidated; this might provide insights to develop new
      drugs to target PDI. This study attempts to perceive the mode of binding of
      dithionitrobenzoic acid (DTNB), and its structurally related compounds on PDI
      enzyme. RESULTS: We performed molecular docking simulation with six different
      inhibitors (ligand), which includes DTNB, NSC695265, thionitrobenzoic acid, 2
      nitro-5-thiocyanobenzoic acid, 2-nitro-5-sulfo-sulfonyl-benzoic acid and
      NSC517871 into the redox-active site [C37-G38-H39-C40] of the PDI enzyme and the
      activity was inferred by redox inhibitory models. All ligands showed favorable
      interactions and most of them seemed to bind to hydrophobic amino acids Ala34,
      Trp36, Cys37, Cys40, His39, Thr68 and Phe80. The redox inhibitory conformations
      were energetically and statistically favored and supported the evidence from wet
      laboratory experiments reported in the literature. CONCLUSION: We demonstrated
      that in silico docking experiment can be effectively carried out to recognize the
      redox inhibitory models of PDI with inhibitor molecules. Interestingly we found
      that number of docked clusters with each ligand varies in the range of five to
      eight and conveys that the binding specificity of each inhibitor varies for PDI.
      We also identified that Cys37 of the enzyme plays an important role in hydrogen
      bonding with inhibitors. This residue can be considered to being an active site
      for anti-HIV drug design. Therefore, by inhibiting PDI, one can, not only prevent
      the viral entry but also circumvent the problem of viral resistance.

PMID- 19091014
TI  - Flanking signal and mature peptide residues influence signal peptide cleavage.
AB  - BACKGROUND: Signal peptides (SPs) mediate the targeting of secretory precursor
      proteins to the correct subcellular compartments in prokaryotes and eukaryotes.
      Identifying these transient peptides is crucial to the medical, food and beverage
      and biotechnology industries yet our understanding of these peptides remains
      limited. This paper examines the most common type of signal peptides cleavable by
      the endoprotease signal peptidase I (SPase I), and the residues flanking the
      cleavage sites of three groups of signal peptide sequences, namely (i) eukaryotes
      (Euk) (ii) Gram-positive (Gram+) bacteria, and (iii) Gram-negative (Gram-)
      bacteria. RESULTS: In this study, 2352 secretory peptide sequences from a variety
      of organisms with amino-terminal SPs are extracted from the manually curated SPdb
      database for analysis based on physicochemical properties such as pI, aliphatic
      index, GRAVY score, hydrophobicity, net charge and position-specific residue
      preferences. Our findings show that the three groups share several similarities
      in general, but they display distinctive features upon examination in terms of
      their amino acid compositions and frequencies, and various physico-chemical
      properties. Thus, analysis or prediction of their sequences should be separated
      and treated as distinct groups. CONCLUSION: We conclude that the peptide segment
      recognized by SPase I extends to the start of the mature protein to a limited
      extent, upon our survey of the amino acid residues surrounding the cleavage
      processing site. These flanking residues possibly influence the cleavage
      processing and contribute to non-canonical cleavage sites. Our findings are
      applicable in defining more accurate prediction tools for recognition and
      identification of cleavage site of SPs.

PMID- 19091015
TI  - Predicted mouse peroxisome-targeted proteins and their actual subcellular
      locations.
AB  - BACKGROUND: The import of most intraperoxisomal proteins is mediated by
      peroxisome targeting signals at their C-termini (PTS1) or N-terminal regions
      (PTS2). Both signals have been integrated in subcellular location prediction
      programs. However their present performance, particularly of PTS2-targeting did
      not seem fitting for large-scale screening of sequences. RESULTS: We modified an
      earlier reported PTS1 screening method to identify PTS2-containing mouse
      candidates using a combination of computational and manual annotation. For rapid
      confirmation of five new PTS2- and two previously identified PTS1-containing
      candidates we developed the new cell line CHO-perRed which stably expresses the
      peroxisomal marker dsRed-PTS1. Using CHO-perRed we confirmed the peroxisomal
      localization of PTS1-targeted candidate Zadh2. Preliminary characterization of
      Zadh2 expression suggested non-PPARalpha mediated activation. Notably, none of
      the PTS2 candidates located to peroxisomes. CONCLUSION: In a few cases the PTS
      may oscillate from "silent" to "functional" depending on its surface
      accessibility indicating the potential for context-dependent conditional
      subcellular sorting. Overall, PTS2-targeting predictions are unlikely to improve
      without generation and integration of new experimental data from location
      proteomics, protein structures and quantitative Pex7 PTS2 peptide binding assays.

PMID- 19091016
TI  - Dynamic sensitivity analysis of biological systems.
AB  - BACKGROUND: A mathematical model to understand, predict, control, or even design
      a real biological system is a central theme in systems biology. A dynamic
      biological system is always modeled as a nonlinear ordinary differential equation
      (ODE) system. How to simulate the dynamic behavior and dynamic parameter
      sensitivities of systems described by ODEs efficiently and accurately is a
      critical job. In many practical applications, e.g., the fed-batch fermentation
      systems, the system admissible input (corresponding to independent variables of
      the system) can be time-dependent. The main difficulty for investigating the
      dynamic log gains of these systems is the infinite dimension due to the time
      dependent input. The classical dynamic sensitivity analysis does not take into
      account this case for the dynamic log gains. RESULTS: We present an algorithm
      with an adaptive step size control that can be used for computing the solution
      and dynamic sensitivities of an autonomous ODE system simultaneously. Although
      our algorithm is one of the decouple direct methods in computing dynamic
      sensitivities of an ODE system, the step size determined by model equations can
      be used on the computations of the time profile and dynamic sensitivities with
      moderate accuracy even when sensitivity equations are more stiff than model
      equations. To show this algorithm can perform the dynamic sensitivity analysis on
      very stiff ODE systems with moderate accuracy, it is implemented and applied to
      two sets of chemical reactions: pyrolysis of ethane and oxidation of
      formaldehyde. The accuracy of this algorithm is demonstrated by comparing the
      dynamic parameter sensitivities obtained from this new algorithm and from the
      direct method with Rosenbrock stiff integrator based on the indirect method. The
      same dynamic sensitivity analysis was performed on an ethanol fed-batch
      fermentation system with a time-varying feed rate to evaluate the applicability
      of the algorithm to realistic models with time-dependent admissible input.
      CONCLUSION: By combining the accuracy we show with the efficiency of being a
      decouple direct method, our algorithm is an excellent method for computing
      dynamic parameter sensitivities in stiff problems. We extend the scope of
      classical dynamic sensitivity analysis to the investigation of dynamic log gains
      of models with time-dependent admissible input.

PMID- 19091017
TI  - Semi-automatic conversion of BioProp semantic annotation to PASBio annotation.
AB  - BACKGROUND: Semantic role labeling (SRL) is an important text analysis technique.
      In SRL, sentences are represented by one or more predicate-argument structures
      (PAS). Each PAS is composed of a predicate (verb) and several arguments (noun
      phrases, adverbial phrases, etc.) with different semantic roles, including main
      arguments (agent or patient) as well as adjunct arguments (time, manner, or
      location). PropBank is the most widely used PAS corpus and annotation format in
      the newswire domain. In the biomedical field, however, more detailed and
      restrictive PAS annotation formats such as PASBio are popular. Unfortunately, due
      to the lack of an annotated PASBio corpus, no publicly available machine-learning
      (ML) based SRL systems based on PASBio have been developed. In previous work, we
      constructed a biomedical corpus based on the PropBank standard called BioProp, on
      which we developed an ML-based SRL system, BIOSMILE. In this paper, we aim to
      build a system to convert BIOSMILE's BioProp annotation output to PASBio
      annotation. Our system consists of BIOSMILE in combination with a BioProp-PASBio
      rule-based converter, and an additional semi-automatic rule generator. RESULTS:
      Our first experiment evaluated our rule-based converter's performance
      independently from BIOSMILE performance. The converter achieved an F-score of
      85.29%. The second experiment evaluated combined system (BIOSMILE + rule-based
      converter). The system achieved an F-score of 69.08% for PASBio's 29 verbs.
      CONCLUSION: Our approach allows PAS conversion between BioProp and PASBio
      annotation using BIOSMILE alongside our newly developed semi-automatic rule
      generator and rule-based converter. Our system can match the performance of other
      state-of-the-art domain-specific ML-based SRL systems and can be easily
      customized for PASBio application development.

PMID- 19091018
TI  - An integrated database-pipeline system for studying single nucleotide
      polymorphisms and diseases.
AB  - BACKGROUND: Studies on the relationship between disease and genetic variations
      such as single nucleotide polymorphisms (SNPs) are important. Genetic variations
      can cause disease by influencing important biological regulation processes.
      Despite the needs for analyzing SNP and disease correlation, most existing
      databases provide information only on functional variants at specific locations
      on the genome, or deal with only a few genes associated with disease. There is no
      combined resource to widely support gene-, SNP-, and disease-related information,
      and to capture relationships among such data. Therefore, we developed an
      integrated database-pipeline system for studying SNPs and diseases. RESULTS: To
      implement the pipeline system for the integrated database, we first unified
      complicated and redundant disease terms and gene names using the Unified Medical
      Language System (UMLS) for classification and noun modification, and the HUGO
      Gene Nomenclature Committee (HGNC) and NCBI gene databases. Next, we collected
      and integrated representative databases for three categories of information. For
      genes and proteins, we examined the NCBI mRNA, UniProt, UCSC Table Track and
      MitoDat databases. For genetic variants we used the dbSNP, JSNP, ALFRED, and
      HGVbase databases. For disease, we employed OMIM, GAD, and HGMD databases. The
      database-pipeline system provides a disease thesaurus, including genes and SNPs
      associated with disease. The search results for these categories are available on
      the web page http://diseasome.kobic.re.kr/, and a genome browser is also
      available to highlight findings, as well as to permit the convenient review of
      potentially deleterious SNPs among genes strongly associated with specific
      diseases and clinical phenotypes. CONCLUSION: Our system is designed to capture
      the relationships between SNPs associated with disease and disease-causing genes.
      The integrated database-pipeline provides a list of candidate genes and SNP
      markers for evaluation in both epidemiological and molecular biological
      approaches to diseases-gene association studies. Furthermore, researchers then
      can decide semi-automatically the data set for association studies while
      considering the relationships between genetic variation and diseases. The
      database can also be economical for disease-association studies, as well as to
      facilitate an understanding of the processes which cause disease. Currently, the
      database contains 14,674 SNP records and 109,715 gene records associated with
      human diseases and it is updated at regular intervals.

PMID- 19091019
TI  - Using a kernel density estimation based classifier to predict species-specific
      microRNA precursors.
AB  - BACKGROUND: MicroRNAs (miRNAs) are short non-coding RNA molecules participating
      in post-transcriptional regulation of gene expression. There have been many
      efforts to discover miRNA precursors (pre-miRNAs) over the years. Recently, ab
      initio approaches obtain more attention because that they can discover species
      specific pre-miRNAs. Most ab initio approaches proposed novel features to
      characterize RNA molecules. However, there were fewer discussions on the
      associated classification mechanism in a miRNA predictor. RESULTS: This study
      focuses on the classification algorithm for miRNA prediction. We develop a novel
      ab initio method, miR-KDE, in which most of the features are collected from
      previous works. The classification mechanism in miR-KDE is the relaxed variable
      kernel density estimator (RVKDE) that we have recently proposed. When compared to
      the famous support vector machine (SVM), RVKDE exploits more local information of
      the training dataset. MiR-KDE is evaluated using a training set consisted of only
      human pre-miRNAs to predict a benchmark collected from 40 species. The
      experimental results show that miR-KDE delivers favorable performance in
      predicting human pre-miRNAs and has advantages for pre-miRNAs from the genera
      taxonomically distant to humans. CONCLUSION: We use a novel classifier of which
      the characteristic of exploiting local information is particularly suitable to
      predict species-specific pre-miRNAs. This study also provides a comprehensive
      analysis from the view of classification mechanism. The good performance of miR
      KDE encourages more efforts on the classification methodology as well as the
      feature extraction in miRNA prediction.

PMID- 19091020
TI  - Ab-origin: an enhanced tool to identify the sourcing gene segments in germline
      for rearranged antibodies.
AB  - BACKGROUND: In the adaptive immune system, variable regions of immunoglobulin
      (IG) are encoded by random recombination of variable (V), diversity (D), and
      joining (J) gene segments in the germline. Partitioning the functional antibody
      sequences to their sourcing germline gene segments is vital not only for
      understanding antibody maturation but also for promoting the potential
      engineering of the therapeutic antibodies. To date, several tools have been
      developed to perform such "trace-back" calculations. Yet, the predicting ability
      and processing volume of those tools vary significantly for different sets of
      data. Moreover, none of them give a confidence for immunoglobulin heavy diversity
      (IGHD) identification. Developing fast, efficient and enhanced tools is always
      needed with the booming of immunological data. RESULTS: Here, a program named Ab
      origin is presented. It is designed by batch query against germline databases
      based on empirical knowledge, optimized scoring scheme and appropriate
      parameters. Special efforts have been paid to improve the identification accuracy
      of the short and volatile region, IGHD. In particular, a threshold score for
      certain sensitivity and specificity is provided to give the confidence level of
      the IGHD identification. CONCLUSION: When evaluated using different sets of both
      simulated data and experimental data, Ab-origin outperformed all the other five
      popular tools in terms of prediction accuracy. The features of batch query and
      confidence indication of IGHD identification would provide extra help to users.
      The program is freely available at http://mpsq.biosino.org/ab
      origin/supplementary.html.

PMID- 19091021
TI  - The value of position-specific scoring matrices for assessment of protein
      allegenicity.
AB  - BACKGROUND: Bioinformatics tools are commonly used for assessing potential
      protein allergenicity. While these methods have achieved good accuracies for
      highly conserved sequences, they are less effective when the overall similarity
      is low. In this study, we assessed the feasibility of using position-specific
      scoring matrices as a basis for predicting potential allergenicity in proteins.
      RESULTS: Two simple methods for predicting potential allergenicity in proteins,
      based on general and group-specific allergen profiles, are presented. Testing
      results indicate that the performances of both methods are comparable to the best
      results of other methods. The group-specific profile approach, with a sensitivity
      of 84.04% and specificity of 96.52%, gives similar results as those obtained
      using the general profile approach (sensitivity = 82.45%, specificity = 96.92%).
      CONCLUSION: We show that position-specific scoring matrices are highly promising
      for constructing computational models suitable for allergenicity assessment.
      These data suggest it may be possible to apply a targeted approach for
      allergenicity assessment based on the profiles of allergens of interest.

PMID- 19091023
TI  - A protein interaction based model for schizophrenia study.
AB  - BACKGROUND: Schizophrenia is a complex disease with multiple factors contributing
      to its pathogenesis. In addition to environmental factors, genetic factors may
      also increase susceptibility. In other words, schizophrenia is a highly heritable
      disease. Some candidate genes have been deduced on the basis of their known
      function with others found on the basis of chromosomal location. Individuals with
      multiple candidate genes may have increased risk. However it is not clear what
      kind of gene combinations may produce the disease phenotype. Their collective
      effect remains to be studied. RESULTS: Most pathways except metabolic pathways
      are rich in protein-protein interactions (PPIs). Thus, the PPI network contains
      pathway information, even though the upstream-downstream relation of PPI is yet
      to be explored. Here we have constructed a PPI sub-network by extracting the
      nearest neighbour of the 36 reported candidate genes described in the literature.
      Although these candidate genes were discovered by different approaches, most of
      the proteins formed a cluster. Two major protein interaction modules were
      identified on the basis of the pairwise distance among the proteins in this sub
      network. The large and small clusters might play roles in synaptic transmission
      and signal transduction, respectively, based on gene ontology annotation. The
      protein interactions in the synaptic transmission cluster were used to explain
      the interaction between the NRG1 and CACNG2 genes, which was found by both
      linkage and association studies. This working hypothesis is supported by the co
      expression analysis based on public microarray gene expression. CONCLUSION: On
      the basis of the protein interaction network, it appears that the NRG1-triggered
      NMDAR protein internalization and the CACNG2 mediated AMPA receptor recruiting
      may act together in the glutamatergic signalling process. Since both the NMDA and
      AMPA receptors are calcium channels, this process may regulate the influx of
      Ca2+. Reducing the cation influx might be one of the disease mechanisms for
      schizophrenia. This PPI network analysis approach combined with the support from
      co-expression analysis may provide an efficient way to propose pathogenetic
      mechanisms for various highly heritable diseases.

PMID- 19091022
TI  - Evaluation of MHC-II peptide binding prediction servers: applications for vaccine
      research.
AB  - BACKGROUND: Initiation and regulation of immune responses in humans involves
      recognition of peptides presented by human leukocyte antigen class II (HLA-II)
      molecules. These peptides (HLA-II T-cell epitopes) are increasingly important as
      research targets for the development of vaccines and immunotherapies. HLA-II
      peptide binding studies involve multiple overlapping peptides spanning individual
      antigens, as well as complete viral proteomes. Antigen variation in pathogens and
      tumor antigens, and extensive polymorphism of HLA molecules increase the number
      of targets for screening studies. Experimental screening methods are expensive
      and time consuming and reagents are not readily available for many of the HLA
      class II molecules. Computational prediction methods complement experimental
      studies, minimize the number of validation experiments, and significantly speed
      up the epitope mapping process. We collected test data from four independent
      studies that involved 721 peptide binding assays. Full overlapping studies of
      four antigens identified binding affinity of 103 peptides to seven common HLA-DR
      molecules (DRB1*0101, 0301, 0401, 0701, 1101, 1301, and 1501). We used these data
      to analyze performance of 21 HLA-II binding prediction servers accessible through
      the WWW. RESULTS: Because not all servers have predictors for all tested HLA-II
      molecules, we assessed a total of 113 predictors. The length of test peptides
      ranged from 15 to 19 amino acids. We tried three prediction strategies - the best
      9-mer within the longer peptide, the average of best three 9-mer predictions, and
      the average of all 9-mer predictions within the longer peptide. The best strategy
      was the identification of a single best 9-mer within the longer peptide. Overall,
      measured by the receiver operating characteristic method (AROC), 17 predictors
      showed good (AROC > 0.8), 41 showed marginal (AROC > 0.7), and 55 showed poor
      performance (AROC < 0.7). Good performance predictors included HLA-DRB1*0101
      (seven), 1101 (six), 0401 (three), and 0701 (one). The best individual predictor
      was NETMHCIIPAN, closely followed by PROPRED, IEDB (Consensus), and MULTIPRED
      (SVM). None of the individual predictors was shown to be suitable for prediction
      of promiscuous peptides. Current predictive capabilities allow prediction of only
      50% of actual T-cell epitopes using practical thresholds. CONCLUSION: The
      available HLA-II servers do not match prediction capabilities of HLA-I
      predictors. Currently available HLA-II prediction servers offer only a limited
      prediction accuracy and the development of improved predictors is needed for
      large-scale studies, such as proteome-wide epitope mapping. The requirements for
      accuracy of HLA-II binding predictions are stringent because of the substantial
      effect of false positives.

PMID- 19091024
TI  - An integrated Korean biodiversity and genetic information retrieval system.
AB  - BACKGROUND: On-line biodiversity information databases are growing quickly and
      being integrated into general bioinformatics systems due to the advances of fast
      gene sequencing technologies and the Internet. These can reduce the cost and
      effort of performing biodiversity surveys and genetic searches, which allows
      scientists to spend more time researching and less time collecting and
      maintaining data. This will cause an increased rate of knowledge build-up and
      improve conservations. The biodiversity databases in Korea have been scattered
      among several institutes and local natural history museums with incompatible data
      types. Therefore, a comprehensive database and a nation wide web portal for
      biodiversity information is necessary in order to integrate diverse information
      resources, including molecular and genomic databases. RESULTS: The Korean Natural
      History Research Information System (NARIS) was built and serviced as the central
      biodiversity information system to collect and integrate the biodiversity data of
      various institutes and natural history museums in Korea. This database aims to be
      an integrated resource that contains additional biological information, such as
      genome sequences and molecular level diversity. Currently, twelve institutes and
      museums in Korea are integrated by the DiGIR (Distributed Generic Information
      Retrieval) protocol, with Darwin Core2.0 format as its metadata standard for data
      exchange. Data quality control and statistical analysis functions have been
      implemented. In particular, integrating molecular and genetic information from
      the National Center for Biotechnology Information (NCBI) databases with NARIS was
      recently accomplished. NARIS can also be extended to accommodate other institutes
      abroad, and the whole system can be exported to establish local biodiversity
      management servers. CONCLUSION: A Korean data portal, NARIS, has been developed
      to efficiently manage and utilize biodiversity data, which includes genetic
      resources. NARIS aims to be integral in maximizing bio-resource utilization for
      conservation, management, research, education, industrial applications, and
      integration with other bioinformation data resources. It can be found at
      http://www.naris.go.kr.

PMID- 19091025
TI  - CMKb: a web-based prototype for integrating Australian Aboriginal customary
      medicinal plant knowledge.
AB  - BACKGROUND: The customary medicinal plant knowledge possessed by the Australian
      Aboriginal people is a significant resource. Published information on it is
      scattered throughout the literature, in heterogeneous data formats, and is
      scattered among various Aboriginal communities across Australia, due to a
      multiplicity of languages. This ancient knowledge is at risk due to loss of
      biodiversity, cultural impact and the demise of many of its custodians. We have
      developed the Customary Medicinal Knowledgebase (CMKb), an integrated
      multidisciplinary resource, to document, conserve and disseminate this knowledge.
      DESCRIPTION: CMKb is an online relational database for collating, disseminating,
      visualising and analysing initially public domain data on customary medicinal
      plants. The database stores information related to taxonomy, phytochemistry,
      biogeography, biological activities of customary medicinal plant species as well
      as images of individual species. The database can be accessed at
      http://biolinfo.org/cmkb. Known bioactive molecules are characterized within the
      chemoinformatics module of CMKb, with functions available for molecular editing
      and visualization. CONCLUSION: CMKb has been developed as a prototype data
      resource for documenting, integrating, disseminating, analysing multidisciplinary
      customary medicinal plant data from Australia and to facilitate user-defined
      complex querying. Each species in CMKb is linked to online resources such as the
      Integrated Taxonomic Information System (ITIS), NCBI Taxonomy, Australia's
      SpeciesLinks-Integrated Botanical Information System (IBIS) and Google images.
      The bioactive compounds are linked to the PubChem database. Overall, CMKb serves
      as a single knowledgebase for holistic plant-derived therapeutics and can be used
      as an information resource for biodiversity conservation, to lead discovery and
      conservation of customary medicinal knowledge.

PMID- 19091026
TI  - Filtering of false positive microRNA candidates by a clustering-based approach.
AB  - BACKGROUND: MicroRNAs are small non-coding RNA gene products that play
      diversified roles from species to species. The explosive growth of microRNA
      researches in recent years proves the importance of microRNAs in the biological
      system and it is believed that microRNAs have valuable therapeutic potentials in
      human diseases. Continual efforts are therefore required to locate and verify the
      unknown microRNAs in various genomes. As many miRNAs are found to be arranged in
      clusters, meaning that they are in close proximity with their neighboring miRNAs,
      we are interested in utilizing the concept of microRNA clustering and applying it
      in microRNA computational prediction. RESULTS: We first validate the microRNA
      clustering phenomenon in the human, mouse and rat genomes. There are 45.45%,
      51.86% and 48.67% of the total miRNAs that are clustered in the three genomes,
      respectively. We then conduct sequence and secondary structure similarity
      analyses among clustered miRNAs, non-clustered miRNAs, neighboring sequences of
      clustered miRNAs and random sequences, and find that clustered miRNAs are
      structurally more similar to one another, and the RNAdistance score can be used
      to assess the structural similarity between two sequences. We therefore design a
      clustering-based approach which utilizes this observation to filter false
      positives from a list of candidates generated by a selected microRNA prediction
      program, and successfully raise the positive predictive value by a considerable
      amount ranging from 15.23% to 23.19% in the human, mouse and rat genomes, while
      keeping a reasonably high sensitivity. CONCLUSION: Our clustering-based approach
      is able to increase the effectiveness of currently available microRNA prediction
      program by raising the positive predictive value while maintaining a high
      sensitivity, and hence can serve as a filtering step. We believe that it is
      worthwhile to carry out further experiments and tests with our approach using
      data from other genomes and other prediction software tools. Better results may
      be achieved with fine-tuning of parameters.

PMID- 19091027
TI  - MiRTif: a support vector machine-based microRNA target interaction filter.
AB  - BACKGROUND: MicroRNAs (miRNAs) are a set of small non-coding RNAs serving as
      important negative gene regulators. In animals, miRNAs turn down protein
      translation by binding to the 3' UTR regions of target genes with imperfect
      complementary pairing. The identification of microRNA targets has become one of
      the major challenges of miRNA research. Bioinformatics investigations on miRNA
      target have resulted in a number of target prediction tools. Although these tools
      are capable of predicting hundreds of targets for a given miRNA, many of them
      suffer from high false positive rates, indicating the need for a post-processing
      filter for the predicted targets. Once trained with experimentally validated true
      and false targets, machine learning methods appear to be ideal approaches to
      distinguish the true targets from the false ones. RESULTS: We present a miRNA
      target filtering system named MiRTif (miRNA:target interaction filter). The
      system is a support vector machine (SVM) classifier trained with 195 positive and
      38 negative miRNA:target interaction pairs, all experimentally validated. Each
      miRNA:target interaction pair is divided into a seed and a non-seed region. The
      encoded feature vector contains various k-gram frequencies in the seed, the non
      seed and the entire regions. Informative features are selected based on their
      discriminating abilities. Prediction accuracies are assessed using 10-fold cross
      validation experiments. Our system achieves AUC (area under the ROC curve) of
      0.86, sensitivity of 83.59%, and specificity of 73.68%. More importantly, the
      system correctly predicts majority of the false positive miRNA:target
      interactions (28 out of 38). The possibility of over-fitting due to the
      relatively small negative sample set has also been investigated using a set of
      non-validated and randomly selected targets (from miRBase). CONCLUSION: MiRTif is
      designed as a post-processing filter that takes miRNA:target interactions
      predicted by other target prediction softwares such as TargetScanS, PicTar and
      miRanda as inputs, and determines how likely the given interaction is a real or a
      pseudo one. MiRTif can be accessed from http://bsal.ym.edu.tw/mirtif.

PMID- 19091028
TI  - Finding microRNA regulatory modules in human genome using rule induction.
AB  - BACKGROUND: MicroRNAs (miRNAs) are a class of small non-coding RNA molecules (20
      24 nt), which are believed to participate in repression of gene expression. They
      play important roles in several biological processes (e.g. cell death and cell
      growth). Both experimental and computational approaches have been used to
      determine the function of miRNAs in cellular processes. Most efforts have
      concentrated on identification of miRNAs and their target genes. However,
      understanding the regulatory mechanism of miRNAs in the gene regulatory network
      is also essential to the discovery of functions of miRNAs in complex cellular
      systems. To understand the regulatory mechanism of miRNAs in complex cellular
      systems, we need to identify the functional modules involved in complex
      interactions between miRNAs and their target genes. RESULTS: We propose a rule
      based learning method to identify groups of miRNAs and target genes that are
      believed to participate cooperatively in the post-transcriptional gene
      regulation, so-called miRNA regulatory modules (MRMs). Applying our method to
      human genes and miRNAs, we found 79 MRMs. The MRMs are produced from multiple
      information sources, including miRNA-target binding information, gene expression
      and miRNA expression profiles. Analysis of two first MRMs shows that these MRMs
      consist of highly-related miRNAs and their target genes with respect to
      biological processes. CONCLUSION: The MRMs found by our method have high
      correlation in expression patterns of miRNAs as well as mRNAs. The mRNAs included
      in the same module shared similar biological functions, indicating the ability of
      our method to detect functionality-related genes. Moreover, review of the
      literature reveals that miRNAs in a module are involved in several types of human
      cancer.

PMID- 19091029
TI  - Predicting RNA-binding sites of proteins using support vector machines and
      evolutionary information.
AB  - BACKGROUND: RNA-protein interaction plays an essential role in several biological
      processes, such as protein synthesis, gene expression, posttranscriptional
      regulation and viral infectivity. Identification of RNA-binding sites in proteins
      provides valuable insights for biologists. However, experimental determination of
      RNA-protein interaction remains time-consuming and labor-intensive. Thus,
      computational approaches for prediction of RNA-binding sites in proteins have
      become highly desirable. Extensive studies of RNA-binding site prediction have
      led to the development of several methods. However, they could yield low
      sensitivities in trade-off for high specificities. RESULTS: We propose a method,
      RNAProB, which incorporates a new smoothed position-specific scoring matrix
      (PSSM) encoding scheme with a support vector machine model to predict RNA-binding
      sites in proteins. Besides the incorporation of evolutionary information from
      standard PSSM profiles, the proposed smoothed PSSM encoding scheme also considers
      the correlation and dependency from the neighboring residues for each amino acid
      in a protein. Experimental results show that smoothed PSSM encoding significantly
      enhances the prediction performance, especially for sensitivity. Using five-fold
      cross-validation, our method performs better than the state-of-the-art systems by
      4.90%-6.83%, 0.88%-5.33%, and 0.10-0.23 in terms of overall accuracy,
      specificity, and Matthew's correlation coefficient, respectively. Most notably,
      compared to other approaches, RNAProB significantly improves sensitivity by 7.0%
      26.9% over the benchmark data sets. To prevent data over fitting, a three-way
      data split procedure is incorporated to estimate the prediction performance.
      Moreover, physicochemical properties and amino acid preferences of RNA-binding
      proteins are examined and analyzed. CONCLUSION: Our results demonstrate that
      smoothed PSSM encoding scheme significantly enhances the performance of RNA
      binding site prediction in proteins. This also supports our assumption that
      smoothed PSSM encoding can better resolve the ambiguity of discriminating between
      interacting and non-interacting residues by modelling the dependency from
      surrounding residues. The proposed method can be used in other research areas,
      such as DNA-binding site prediction, protein-protein interaction, and prediction
      of posttranslational modification sites.

PMID- 19091030
TI  - Extracting transcription factor binding sites from unaligned gene sequences with
      statistical models.
AB  - BACKGROUND: Transcription factor binding sites (TFBSs) are crucial in the
      regulation of gene transcription. Recently, chromatin immunoprecipitation
      followed by cDNA microarray hybridization (ChIP-chip array) has been used to
      identify potential regulatory sequences, but the procedure can only map the
      probable protein-DNA interaction loci within 1-2 kb resolution. To find out the
      exact binding motifs, it is necessary to build a computational method to examine
      the ChIP-chip array binding sequences and search for possible motifs representing
      the transcription factor binding sites. RESULTS: We developed a program to find
      out accurate motif sites from a set of unaligned DNA sequences in the yeast
      genome. Compared with MDscan, the prediction results suggest that, overall, our
      algorithm outperforms MDscan since the predicted motifs are more consistent with
      previously known specificities reported in the literature and have better
      prediction ranks. Our program also outperforms the constraint-less Cosmo program,
      especially in the elimination of false positives. CONCLUSION: In this study, an
      improved sampling algorithm is proposed to incorporate the binomial probability
      model to build significant initial candidate motif sets. By investigating the
      statistical dependence between base positions in TFBSs, the method of dependency
      graphs and their expanded Bayesian networks is combined. The results show that
      our program satisfactorily extract transcription factor binding sites from
      unaligned gene sequences.

PMID- 19091031
TI  - Fast splice site detection using information content and feature reduction.
AB  - BACKGROUND: Accurate identification of splice sites in DNA sequences plays a key
      role in the prediction of gene structure in eukaryotes. Already many
      computational methods have been proposed for the detection of splice sites and
      some of them showed high prediction accuracy. However, most of these methods are
      limited in terms of their long computation time when applied to whole genome
      sequence data. RESULTS: In this paper we propose a hybrid algorithm which
      combines several effective and informative input features with the state of the
      art support vector machine (SVM). To obtain the input features we employ
      information content method based on Shannon's information theory, Shapiro's score
      scheme, and Markovian probabilities. We also use a feature elimination scheme to
      reduce the less informative features from the input data. CONCLUSION: In this
      study we propose a new feature based splice site detection method that shows
      improved acceptor and donor splice site detection in DNA sequences when the
      performance is compared with various state of the art and well known methods.

PMID- 19091032
TI  - VarDetect: a nucleotide sequence variation exploratory tool.
AB  - BACKGROUND: Single nucleotide polymorphisms (SNPs) are the most commonly studied
      units of genetic variation. The discovery of such variation may help to identify
      causative gene mutations in monogenic diseases and SNPs associated with
      predisposing genes in complex diseases. Accurate detection of SNPs requires
      software that can correctly interpret chromatogram signals to nucleotides.
      RESULTS: We present VarDetect, a stand-alone nucleotide variation exploratory
      tool that automatically detects nucleotide variation from fluorescence based
      chromatogram traces. Accurate SNP base-calling is achieved using pre-calculated
      peak content ratios, and is enhanced by rules which account for common sequence
      reading artifacts. The proposed software tool is benchmarked against four other
      well-known SNP discovery software tools (PolyPhred, novoSNP, Genalys and Mutation
      Surveyor) using fluorescence based chromatograms from 15 human genes. These
      chromatograms were obtained from sequencing 16 two-pooled DNA samples; a total of
      32 individual DNA samples. In this comparison of automatic SNP detection tools,
      VarDetect achieved the highest detection efficiency. AVAILABILITY: VarDetect is
      compatible with most major operating systems such as Microsoft Windows, Linux,
      and Mac OSX. The current version of VarDetect is freely available at
      http://www.biotec.or.th/GI/tools/vardetect.

PMID- 19091033
TI  - Towards a research agenda for global malaria elimination.

PMID- 19091034
TI  - Malaria vaccines and their potential role in the elimination of malaria.
AB  - Research on malaria vaccines is currently directed primarily towards the
      development of vaccines that prevent clinical malaria. Malaria elimination, now
      being considered seriously in some epidemiological situations, requires a
      different vaccine strategy, since success will depend on killing all parasites in
      the community in order to stop transmission completely. The feature of the life
      cycles of human malarias that presents the greatest challenge to an elimination
      programme is the persistence of parasites as asymptomatic infections. These are
      an important source from which transmission to mosquitoes can occur.
      Consequently, an elimination strategy requires a community-based approach
      covering all individuals and not just those who are susceptible to clinical
      malaria. The progress that has been made in development of candidate malaria
      vaccines is reviewed. It is unlikely that many of these will have the efficacy
      required for complete elimination of parasites, though they may have an important
      role to play as part of future integrated control programmes. Vaccines for
      elimination must have a high level of efficacy in order to stop transmission to
      mosquitoes. This might be achieved with some pre-erythrocytic stage candidate
      vaccines or by targeting the sexual stages directly with transmission-blocking
      vaccines. An expanded malaria vaccine programme with such objectives is now a
      priority.

PMID- 19091035
TI  - Malaria eradication: the economic, financial and institutional challenge.
AB  - Malaria eradication raises many economic, financial and institutional challenges.
      This paper reviews these challenges, drawing on evidence from previous efforts to
      eradicate malaria, with a special focus on resource-poor settings; summarizes
      more recent evidence on the challenges, drawing on the literature on the
      difficulties of scaling-up malaria control and strengthening health systems more
      broadly; and explores the implications of these bodies of evidence for the
      current call for elimination and intensified control. Economic analyses dating
      from the eradication era, and more recent analyses, suggest that, in general, the
      benefits of malaria control outweigh the costs, though few studies have looked at
      the relative returns to eradication versus long-term control. Estimates of
      financial costs are scanty and difficult to compare. In the 1960s, the
      consolidation phase appeared to cost less than $1 per capita and, in 1988, was
      estimated to be $2.31 per capita (both in 2006 prices). More recent estimates for
      high coverage of control measures suggest a per capita cost of several dollars.
      Institutional challenges faced by malaria eradication included limits to the rule
      of law (a major problem where malaria was concentrated in border areas with
      movement of people associated with illegal activities), the existence and
      performance of local implementing structures, and political sustainability at
      national and global levels. Recent analyses of the constraints to scaling-up
      malaria control, together with the historical evidence, are used to discuss the
      economic, financial and institutional challenges that face the renewed call for
      eradication and intensified control. The paper concludes by identifying a
      research agenda covering: issues of the allocative efficiency of malaria
      eradication, especially using macro-economic modelling to estimate the benefits
      and costs of malaria eradication and intensified control, and studies of the
      links between malaria control and economic development, the costs and
      consequences of the various tools and mixes of tools employed in control and
      eradication, issues concerning the extension of coverage of interventions and
      service delivery approaches, especially those that can reach the poorest,
      research on the processes of formulating and implementing malaria control and
      eradication policies, at both international and national levels, research on
      financing issues, at global and national levels.

PMID- 19091036
TI  - A golden age for malaria research and innovation.

PMID- 19091037
TI  - Global warming and malaria: knowing the horse before hitching the cart.
AB  - Speculations on the potential impact of climate change on human health frequently
      focus on malaria. Predictions are common that in the coming decades, tens - even
      hundreds - of millions more cases will occur in regions where the disease is
      already present, and that transmission will extend to higher latitudes and
      altitudes. Such predictions, sometimes supported by simple models, are persuasive
      because they are intuitive, but they sidestep factors that are key to the
      transmission and epidemiology of the disease: the ecology and behaviour of both
      humans and vectors, and the immunity of the human population. A holistic view of
      the natural history of the disease, in the context of these factors and in the
      precise setting where it is transmitted, is the only valid starting point for
      assessing the likely significance of future changes in climate.

PMID- 19091038
TI  - Integrated vector management for malaria control.
AB  - Integrated vector management (IVM) is defined as "a rational decision-making
      process for the optimal use of resources for vector control" and includes five
      key elements: 1) evidence-based decision-making, 2) integrated approaches 3),
      collaboration within the health sector and with other sectors, 4) advocacy,
      social mobilization, and legislation, and 5) capacity-building. In 2004, the WHO
      adopted IVM globally for the control of all vector-borne diseases. Important
      recent progress has been made in developing and promoting IVM for national
      malaria control programmes in Africa at a time when successful malaria control
      programmes are scaling-up with insecticide-treated nets (ITN) and/or indoor
      residual spraying (IRS) coverage. While interventions using only ITNs and/or IRS
      successfully reduce transmission intensity and the burden of malaria in many
      situations, it is not clear if these interventions alone will achieve those
      critical low levels that result in malaria elimination. Despite the successful
      employment of comprehensive integrated malaria control programmes, further
      strengthening of vector control components through IVM is relevant, especially
      during the "end-game" where control is successful and further efforts are
      required to go from low transmission situations to sustained local and country
      wide malaria elimination. To meet this need and to ensure sustainability of
      control efforts, malaria control programmes should strengthen their capacity to
      use data for decision-making with respect to evaluation of current vector control
      programmes, employment of additional vector control tools in conjunction with
      ITN/IRS tactics, case-detection and treatment strategies, and determine how much
      and what types of vector control and interdisciplinary input are required to
      achieve malaria elimination. Similarly, on a global scale, there is a need for
      continued research to identify and evaluate new tools for vector control that can
      be integrated with existing biomedical strategies within national malaria control
      programmes. This review provides an overview of how IVM programmes are being
      implemented, and provides recommendations for further development of IVM to meet
      the goals of national malaria control programmes in Africa.

PMID- 19091039
TI  - Working without a blindfold: the critical role of diagnostics in malaria control.
AB  - Diagnostic testing for malaria has for many years been eschewed, lest it be an
      obstacle to the delivery of rapid, life-saving treatment. The approach of
      treating malaria without confirmatory testing has been reinforced by the
      availability of inexpensive treatment with few side effects, by the great
      difficulty of establishing quality-assured microscopy in rural and resource-poor
      settings, and by the preeminence of malaria as a cause of important fever in
      endemic regions. Within the last decade, all three of these factors have changed.
      More expensive artemisinin combination therapy (ACT) has been widely introduced,
      simple immunochromatographic tests for malaria have been developed that can be
      used as an alternative to microscopy by village health workers, and recognition
      of the health cost of mismanaging non-malarial fever is growing. In most of the
      world a small fraction of fever is due to malaria, and reflex treatment with ACT
      does not make medical or economic sense. Global malaria control efforts have been
      energized by the availability of new sources of funding, and by the rapid
      reduction in malaria prevalence in a number of settings where bed nets, indoor
      residual spraying with insecticides, and ACT have been systematically deployed.
      This momentum has been captured by a new call for malaria elimination. Without
      wide implementation of accurate and discriminating diagnostic testing, and
      reporting of results, most fever will be inappropriately managed, millions of
      doses of ACT will be wasted, and malaria control programmes will be blindfolded
      to the impact of their efforts.

PMID- 19091040
TI  - Monitoring and evaluation of malaria in pregnancy - developing a rational basis
      for control.
AB  - Monitoring and evaluation of malaria control in pregnancy is essential for
      assessing the efficacy and effectiveness of health interventions aimed at
      reducing the major burden of this disease on women living in endemic areas. Yet
      there is no currently integrated strategic approach on how this should be
      achieved. Malaria control in pregnancy is formulated in relation to
      epidemiological patterns of exposure. Current emphasis is on intermittent
      preventive treatment (IPTp) during pregnancy with sulphadoxine-pyrimethamine in
      higher transmission areas, combined with insecticide treated bed nets (ITNs) and
      case management. Emphasis in lower transmission areas is primarily on case
      management. This paper discusses a rational basis for monitoring and evaluation
      based on: assessments of therapeutic and prophylactic drug efficacy; proportional
      reductions in parasite prevalence; seasonal effects; rapid assessment
      methodologies; birthweight and/or anaemia nomograms; case-coverage methods;
      maternal mortality indices; operational and programmatic indicators; and safety
      and pharmacovigilance of antimalarials in pregnancy. These approaches should be
      incorporated more effectively within National Programmes in order to facilitate
      surveillance and improve identification of high-risk women. Systems for utilizing
      routinely collected data should be strengthened, with greater attention to safety
      and pharmacovigilance with the advent of artemisinin combination therapies, and
      prospects of inadvertent exposures to artemisinins in the first trimester.
      Integrating monitoring activities within malaria control, reproductive health and
      adolescent-friendly services will be critical for implementation. Large-scale
      operational research is required to further evaluate the validity of currently
      proposed indicators, and in order to clarify the breadth and scale of
      implementation to be deployed.

PMID- 19091041
TI  - Deployment of ACT antimalarials for treatment of malaria: challenges and
      opportunities.
AB  - Following a long period when the effectiveness of existing mono-therapies for
      antimalarials was steadily declining with no clear alternative, most malaria
      endemic countries in Africa and Asia have adopted artemisinin combination therapy
      (ACT) as antimalarial drug policy. Several ACT drugs exist and others are in the
      pipeline. If properly targeted, they have the potential to reduce mortality from
      malaria substantially. The major challenge now is to get the drugs to the right
      people. Current evidence suggests that most of those who need the drugs do not
      get them. Simultaneously, a high proportion of those who are given antimalarials
      do not in fact have malaria. Financial and other barriers mean that, in many
      settings, the majority of those with malaria, particularly the poorest, do not
      access formal healthcare, so the provision of free antimalarials via this route
      has only limited impact. The higher cost of ACT creates a market for fake drugs.
      Addressing these problems is now a priority. This review outlines current
      evidence, possible solutions and research priorities.

PMID- 19091042
TI  - The role of anti-malarial drugs in eliminating malaria.
AB  - Effective anti-malarial drug treatment reduces malaria transmission. This alone
      can reduce the incidence and prevalence of malaria, although the effects are
      greater in areas of low transmission where a greater proportion of the infectious
      reservoir is symptomatic and receives anti-malarial treatment. Effective
      treatment has greater effects on the transmission of falciparum malaria, where
      gametocytogenesis is delayed, compared with the other human malarias in which
      peak gametocytaemia and transmissibility coincides with peak asexual parasite
      densities. Mature Plasmodium falciparum gametocytes are more drug resistant and
      affected only by artemisinins and 8-aminoquinolines. The key operational question
      now is whether primaquine should be added to artemisinin combination treatments
      for the treatment of falciparum malaria to reduce further the transmissibility of
      the treated infection. Radical treatment with primaquine plays a key role in the
      eradication of vivax and ovale malaria. More evidence is needed on the safety of
      primaquine when administered without screening for G6PD deficiency to inform
      individual and mass treatment approaches in the context of malaria elimination
      programmes.

PMID- 19091044
TI  - The Global Youth Tobacco Survey (GYTS): linking data to the implementation of the
      WHO Framework Convention on Tobacco Control.

PMID- 19091045
TI  - Prevalence of smoking and other smoking related behaviors reported by the Global
      Youth Tobacco Survey (GYTS) in four Peruvian cities.
AB  - INTRODUCTION: In 2004, Peru ratified the Health Organization (WHO) Framework
      Convention on Tobacco Control (FCTC) and in 2006 passed Law 28705 for tobacco
      consumption and exposure reduction. The Global Youth Tobacco Survey (GYTS)
      provides data on youth tobacco use for development of tobacco control programs.
      Findings from the GYTS conducted in four main cities in Peru in 2000 and 2003 are
      reported in this paper and can be used to monitor provisions of the WHO FCTC.
      METHODS: The GYTS is a school-based survey that uses a standardized methodology
      for sampling, questionnaire construction, field procedures, and data management.
      In total, 5,332 and 7,824 students aged 13 to 15 years participated in the 2000
      and 2003 surveys conducted in Huancayo, Lima, Tarapoto and Trujillo. RESULTS: In
      both years, Lima had the highest lifetime (54.6% and 59.6%) and current use of
      tobacco (18.6% and 19.2%) of the four cities. According to gender, boys smoked
      more than girls and less than 20% of students initiated smoking before the age of
      10. Among smokers, more than 60% bought their cigarettes in a store with no
      restriction for their age, and approximately 12% had ever been offered "free
      cigarettes". Around 90% of students were in favor of banning smoking in public
      places. Changes between 2000 and 2003 included an increase in the percentage of
      smokers who wanted to have a cigarette first thing in the morning in Tarapoto
      (from 0% to 1.2%) and a decrease in exposure to tobacco at home in Huancayo (from
      23.7% to 17.8%) and Trujillo (from 27.8% to 19.8%) CONCLUSION: While few changes
      in tobacco use among youth have been observed in the GYTS in Peru, the data in
      this report can be used as baseline measures for future evaluation efforts. At
      this time, tobacco control efforts in Peru need to focus on enhancing Law 28705
      to include enforcement of existing provisions and inclusion of new laws and
      regulations. Most of these provisions are required of all countries, such as
      Peru, that have ratified the WHO FCTC.

PMID- 19091043
TI  - Plasmodium vivax: who cares?
AB  - More attention is being focused on malaria today than any time since the world's
      last efforts to achieve eradication over 40 years ago. The global community is
      now discussing strategies aimed at dramatically reducing malarial disease burden
      and the eventual eradication of all types of malaria, everywhere. As a
      consequence, Plasmodium vivax, which has long been neglected and mistakenly
      considered inconsequential, is now entering into the strategic debates taking
      place on malaria epidemiology and control, drug resistance, pathogenesis and
      vaccines. Thus, contrary to the past, the malaria research community is becoming
      more aware and concerned about the widespread spectrum of illness and death
      caused by up to a couple of hundred million cases of vivax malaria each year.
      This review brings these issues to light and provides an overview of P. vivax
      vaccine development, then and now. Progress had been slow, given inherent
      research challenges and minimal support in the past, but prospects are looking
      better for making headway in the next few years. P. vivax, known to invade the
      youngest red blood cells, the reticulocytes, presents a strong challenge towards
      developing a reliable long-term culture system to facilitate needed research. The
      P. vivax genome was published recently, and vivax researchers now need to
      coordinate efforts to discover new vaccine candidates, establish new vaccine
      approaches, capitalize on non-human primate models for testing, and investigate
      the unique biological features of P. vivax, including the elusive P. vivax
      hypnozoites. Comparative studies on both P. falciparum and P. vivax in many areas
      of research will be essential to eradicate malaria. And to this end, the
      education and training of future generations of dedicated "malariologists" to
      advance our knowledge, understanding and the development of new interventions
      against each of the malaria species infecting humans also will be essential.

PMID- 19091046
TI  - Prevalence of smoking and other smoking-related behaviors reported by the Global
      Youth Tobacco Survey (GYTS) in Thailand.
AB  - INTRODUCTION: Thailand ratified the World Health Organization (WHO) Framework
      Convention on Tobacco Control (FCTC) on November 8, 2004. The WHO FCTC requires
      all parties to inform all persons of the health consequences of tobacco
      consumption and exposure to tobacco smoke. Each party has agreed to develop,
      implement and evaluate effective tobacco control programs to measure progress in
      reaching the goals of the WHO FCTC. METHODS: The Global Youth Tobacco Survey
      (GYTS) was developed to provide data on youth tobacco use to countries for their
      development of youth-based tobacco control programs. Data in this report can be
      used as baseline measures for future evaluation of the tobacco control programs
      implemented by the Ministry of Public Health. RESULTS: Overall, about 1 in 10
      Thai students are current smokers, this number including 4 times more boys than
      girls (17% versus 3.9%). Almost 2 in 10 Thai students start smoking before the
      age of 10, and almost 7 in 10 students are reported to have been exposed to smoke
      from others in public places. About 4 in 10 students are reported to have an
      object with a cigarette brand logo on it. CONCLUSION: The key for Thailand is to
      implement and enforce the provisions on indirect tobacco advertising, smoking in
      public places, selling tobacco to youths under 18 years of age, and to use the
      data from the GYTS to monitor progress toward achieving the goals of the WHO
      FCTC. When these goals are met, tobacco consumption and exposure in Thailand will
      have declined substantially.

PMID- 19091047
TI  - Evaluation of the use of Global Youth Tobacco Survey (GYTS) data for developing
      evidence-based tobacco control policies in Turkey.
AB  - INTRODUCTION: The tobacco control effort in Turkey has made significant progress
      in recent years. Turkey initiated its tobacco control effort with the passing of
      Law 4207 (The Prevention of Harmful Effects of Tobacco Products) in 1996 and
      ratified the World Health Organization (WHO) Framework Convention on Tobacco
      Control (FCTC) in 2004. It is important to base policy decisions on valid and
      reliable evidence from population-based, representative studies that are
      periodically repeated to enable policy makers to monitor the results of their
      interventions and to appropriately tailor anti-tobacco activities towards future
      needs. METHODS: The Global Youth Tobacco Survey (GYTS) was developed to track
      tobacco use among young people and enhance the capacity of countries to design,
      implement, and evaluate tobacco control and prevention programs. Turkey conducted
      the GYTS in 2003 and data from this survey can be used as baseline measures for
      evaluation of the tobacco control programs implemented by the Ministry of Health
      (MOH) of the Turkish government. RESULTS: The GYTS was conducted in 2003 on a
      representative sample of students aged 13 to 15 years. It indicated that almost 3
      in 10 students in Turkey had ever smoked cigarettes, with significantly higher
      rates among boys. Current cigarette smoking rates were lower, at 9% for boys and
      4% for girls. The prevalence of current use of other tobacco products was about
      half these figures for each gender. About 80% were exposed to secondhand smoke.
      Exposure to pro-smoking media messages was not rare. Almost half of the smokers
      'usually' bought their tobacco from a store, despite the law prohibiting this.
      Exposure to teaching against smoking in schools was not universal. CONCLUSION:
      Findings from the GYTS, with periodic repeats of the survey, can be used to
      monitor the impact of enforcing various provisions of the present law (No: 4207),
      the progress made in achieving the goals of the WHO FCTC, and the effectiveness
      of various preventive interventions against smoking. Such data would inform and
      help in the development of public health strategy.

PMID- 19091048
TI  - Machine learning in systems biology.
AB  - This supplement contains extended versions of a selected subset of papers
      presented at the workshop MLSB 2007, Machine Learning in Systems Biology, Evry,
      France, from September 24 to 25, 2007.

PMID- 19091049
TI  - Towards structured output prediction of enzyme function.
AB  - BACKGROUND: In this paper we describe work in progress in developing kernel
      methods for enzyme function prediction. Our focus is in developing so called
      structured output prediction methods, where the enzymatic reaction is the
      combinatorial target object for prediction. We compared two structured output
      prediction methods, the Hierarchical Max-Margin Markov algorithm (HM3) and the
      Maximum Margin Regression algorithm (MMR) in hierarchical classification of
      enzyme function. As sequence features we use various string kernels and the GTG
      feature set derived from the global alignment trace graph of protein sequences.
      RESULTS: In our experiments, in predicting enzyme EC classification we obtain
      over 85% accuracy (predicting the four digit EC code) and over 91% microlabel F1
      score (predicting individual EC digits). In predicting the Gold Standard enzyme
      families, we obtain over 79% accuracy (predicting family correctly) and over 89%
      microlabel F1 score (predicting superfamilies and families). In the latter case,
      structured output methods are significantly more accurate than nearest neighbor
      classifier. A polynomial kernel over the GTG feature set turned out to be a
      prerequisite for accurate function prediction. Combining GTG with string kernels
      boosted accuracy slightly in the case of EC class prediction. CONCLUSION:
      Structured output prediction with GTG features is shown to be computationally
      feasible and to have accuracy on par with state-of-the-art approaches in enzyme
      function prediction.

PMID- 19091050
TI  - Towards a semi-automatic functional annotation tool based on decision-tree
      techniques.
AB  - BACKGROUND: Due to the continuous improvements of high throughput technologies
      and experimental procedures, the number of sequenced genomes is increasing
      exponentially. Ultimately, the task of annotating these data relies on the
      expertise of biologists. The necessity for annotation to be supervised by human
      experts is the rate limiting step of the data analysis. To face the deluge of new
      genomic data, the need for automating, as much as possible, the annotation
      process becomes critical. RESULTS: We consider annotation of a protein with terms
      of the functional hierarchy that has been used to annotate Bacillus subtilis and
      propose a set of rules that predict classes in terms of elements of the
      functional hierarchy, i.e., a class is a node or a leaf of the hierarchy tree.
      The rules are obtained through two decision-trees techniques: first-order
      decision-trees and multilabel attribute-value decision-trees, by using as
      training data the proteins from two lactic bacteria: Lactobacillus sakei and
      Lactobacillus bulgaricus. We tested the two methods, first independently, then in
      a combined approach, and evaluated the obtained results using hierarchical
      evaluation measures. Results obtained for the two approaches on both genomes are
      comparable and show a good precision together with a high prediction rate. Using
      combined approaches increases the recall and the prediction rate. CONCLUSION: The
      combination of the two approaches is very encouraging and we will further refine
      these combinations in order to get rules even more useful for the annotators.
      This first study is a crucial step towards designing a semi-automatic functional
      annotation tool.

PMID- 19091051
TI  - Identification of functional modules based on transcriptional regulation
      structure.
AB  - BACKGROUND: Identifying gene functional modules is an important step towards
      elucidating gene functions at a global scale. Clustering algorithms mostly rely
      on co-expression of genes, that is group together genes having similar expression
      profiles. RESULTS: We propose to cluster genes by co-regulation rather than by co
      expression. We therefore present an inference algorithm for detecting co
      regulated groups from gene expression data and introduce a method to cluster
      genes given that inferred regulatory structure. Finally, we propose to validate
      the clustering through a score based on the GO enrichment of the obtained groups
      of genes. CONCLUSION: We evaluate the methods on the stress response of S.
      Cerevisiae data and obtain better scores than clustering obtained directly from
      gene expression.

PMID- 19091052
TI  - Machine learning techniques to identify putative genes involved in nitrogen
      catabolite repression in the yeast Saccharomyces cerevisiae.
AB  - BACKGROUND: Nitrogen is an essential nutrient for all life forms. Like most
      unicellular organisms, the yeast Saccharomyces cerevisiae transports and
      catabolizes good nitrogen sources in preference to poor ones. Nitrogen catabolite
      repression (NCR) refers to this selection mechanism. All known nitrogen
      catabolite pathways are regulated by four regulators. The ultimate goal is to
      infer the complete nitrogen catabolite pathways. Bioinformatics approaches offer
      the possibility to identify putative NCR genes and to discard uninteresting
      genes. RESULTS: We present a machine learning approach where the identification
      of putative NCR genes in the yeast Saccharomyces cerevisiae is formulated as a
      supervised two-class classification problem. Classifiers predict whether genes
      are NCR-sensitive or not from a large number of variables related to the GATA
      motif in the upstream non-coding sequences of the genes. The positive and
      negative training sets are composed of annotated NCR genes and manually-selected
      genes known to be insensitive to NCR, respectively. Different classifiers and
      variable selection methods are compared. We show that all classifiers make
      significant and biologically valid predictions by comparing these predictions to
      annotated and putative NCR genes, and by performing several negative controls. In
      particular, the inferred NCR genes significantly overlap with putative NCR genes
      identified in three genome-wide experimental and bioinformatics studies.
      CONCLUSION: These results suggest that our approach can successfully identify
      potential NCR genes. Hence, the dimensionality of the problem of identifying all
      genes involved in NCR is drastically reduced.

PMID- 19091053
TI  - Gene-based bin analysis of genome-wide association studies.
AB  - BACKGROUND: With the improvement of genotyping technologies and the exponentially
      growing number of available markers, case-control genome-wide association studies
      promise to be a key tool for investigation of complex diseases. However new
      analytical methods have to be developed to face the problems induced by this data
      scale-up, such as statistical multiple testing, data quality control and
      computational tractability. RESULTS: We present a novel method to analyze genome
      wide association studies results. The algorithm is based on a Bayesian model that
      integrates genotyping errors and genomic structure dependencies. p-values are
      assigned to genomic regions termed bins, which are defined from a gene-biased
      partitioning of the genome, and the false-discovery rate is estimated. We have
      applied this algorithm to data coming from three genome-wide association studies
      of Multiple Sclerosis. CONCLUSION: The method practically overcomes the scale-up
      problems and permits to identify new putative regions statistically associated
      with the disease.

PMID- 19091054
TI  - A marginalized variational bayesian approach to the analysis of array data.
AB  - BACKGROUND: Bayesian unsupervised learning methods have many applications in the
      analysis of biological data. For example, for the cancer expression array
      datasets presented in this study, they can be used to resolve possible disease
      subtypes and to indicate statistically significant dysregulated genes within
      these subtypes. RESULTS: In this paper we outline a marginalized variational
      Bayesian inference method for unsupervised clustering. In this approach latent
      process variables and model parameters are allowed to be dependent. This is
      achieved by marginalizing the mixing Dirichlet variables and then performing
      inference in the reduced variable space. An iterative update procedure is
      proposed. CONCLUSION: Theoretically and experimentally we show that the proposed
      algorithm gives a much better free-energy lower bound than a standard variational
      Bayesian approach. The algorithm is computationally efficient and its performance
      is demonstrated on two expression array data sets.

PMID- 19091055
TI  - Divergence and diversification in North American Psoraleeae (Fabaceae) due to
      climate change.
AB  - BACKGROUND: Past studies in the legume family (Fabaceae) have uncovered several
      evolutionary trends including differential mutation and diversification rates
      across varying taxonomic levels. The legume tribe Psoraleeae is shown herein to
      exemplify these trends at the generic and species levels. This group includes a
      sizable diversification within North America dated at approximately 6.3 million
      years ago with skewed species distribution to the most recently derived genus,
      Pediomelum, suggesting a diversification rate shift. We estimate divergence dates
      of North American (NAm) Psoraleeae using Bayesian MCMC sampling in BEAST based on
      eight DNA regions (ITS, waxy, matK, trnD-trnT, trnL-trnF, trnK, trnS-trnG, and
      rpoB-trnC). We also test the hypothesis of a diversification rate shift within
      NAm Psoraleeae using topological and temporal methods. We investigate the impact
      of climate change on diversification in this group by (1) testing the hypothesis
      that a shift from mesic to xeric habitats acted as a key innovation and (2)
      investigating diversification rate shifts along geologic time, discussing the
      impact of Quaternary climate oscillations on diversification. RESULTS: NAm
      Psoraleeae represents a recent, rapid radiation with several genera originating
      during the Pleistocene, 1 to 2 million years ago. A shift in diversification rate
      is supported by both methods with a 2.67-fold increase suggested around 2 million
      years ago followed by a 8.73-fold decrease 440,000 years ago. The hypothesis that
      a climate regime shift from mesic to xeric habitats drove increased
      diversification in affected taxa was not supported. Timing of the diversification
      rate increase supports the hypothesis that glaciation-induced climate changes
      during the Quaternary influenced diversification of the group. Nonrandom spatial
      diversification also exists, with greater species richness in the American
      Southwest. CONCLUSION: This study outlines NAm Psoraleeae as a model example of a
      recent, rapid radiation. Diversification rate shifts in NAm Psoraleeae are not
      due to current climate regimes as represented by habitat, but instead to past
      global climate change resulting from Quaternary glaciations. NAm Psoraleeae
      diversification is a good example of how earthly dynamics including global
      climate change and topography work together to shape biodiversity.

PMID- 19091056
TI  - Comparative and phylogenomic studies on the mitochondrial genomes of
      Pentatomomorpha (Insecta: Hemiptera: Heteroptera).
AB  - BACKGROUND: Nucleotide sequences and the gene arrangements of mitochondrial
      genomes are effective tools for resolving phylogenetic problems. Hemipteroid
      insects are known to possess highly reorganized mitochondrial genomes, but in the
      suborder Heteroptera (Insecta: Hemiptera), there was only one complete
      mitochondrial genome sequenced without gene rearrangement and the phylogeny of
      infraorder Pentatomomorpha in Heteroptera was still uncertain. RESULTS: Fifteen
      mitochondrial genomes of the suborder Heteroptera were sequenced. Gene
      rearrangements were found as follows: 1) tRNA-I and tRNA-Q switched positions in
      Aradidae, 2) tRNA-T and tRNA-P switched positions in Largidae and Pyrrhocoridae.
      Two recombination events were found in Alydidae and Malcidae. The other mt
      genomes were organized in the same way as observed in Drosophila yakuba. The
      phylogenetic analyses of infraorder Pentatomomorpha based on the nucleotide
      sequence raised the hypothesis of (Aradoidea + (Pentatomoidea + (Pyrrhocoroidea +
      (Lygaeoidea + Coreoidea)))). The rearrangement of tRNA-T and tRNA-P also linked
      Largidae and Pyrrhocoridae together. Furthermore, the conserved sequence block in
      the unusual intergenic spacers between tRNA-H and ND4 favored the monophyly of
      Lygaeoidea. Tetranucleotide ATCA was inferred to be the initiation codon of ND2
      in Cydnidae. No correlation was found between the rates of nucleotide
      substitution and gene rearrangement. CG content was significantly correlated with
      the nucleotide substitution rate of each gene. For ND1, there was a positive
      correlation (P < 0.01) between amino acids variations and hydrophobicity, but a
      negative correlation (P < 0.01) for ND6. No conserved sequence was found among
      the control regions and these regions were not always the most AT-rich region of
      the mt-genome. CONCLUSION: Heteropteran insects are extremely complex groups
      worthy of further study because of the unusual tetranucleotide initiation codon
      and their great mt-genomic diversity, including gene rearrangements and
      recombinations. The mt-genome is a powerful molecular marker for resolving
      phylogeny at the level of the superfamily and family. Gene rearrangements were
      not correlated with nucleotide substitution rates. CG content variation caused
      the different evolutionary patterns among genes. For ND1, in many polar or
      nonpolar regions the specific identity of the amino acid residues might be more
      important than maintaining the polarity of these regions, while the opposite is
      true for ND6. Most sequences of the control regions did not appear to be
      important for regulatory functions. Finally, we suggest that the term "AT-rich
      regions" should not be used.

PMID- 19091058
TI  - Spatial patterns of natural hazards mortality in the United States.
AB  - BACKGROUND: Studies on natural hazard mortality are most often hazard-specific
      (e.g. floods, earthquakes, heat), event specific (e.g. Hurricane Katrina), or
      lack adequate temporal or geographic coverage. This makes it difficult to assess
      mortality from natural hazards in any systematic way. This paper examines the
      spatial patterns of natural hazard mortality at the county-level for the U.S.
      from 1970-2004 using a combination of geographical and epidemiological methods.
      RESULTS: Chronic everyday hazards such as severe weather (summer and winter) and
      heat account for the majority of natural hazard fatalities. The regions most
      prone to deaths from natural hazards are the South and intermountain west, but
      sub-regional county-level mortality patterns show more variability. There is a
      distinct urban/rural component to the county patterns as well as a coastal trend.
      Significant clusters of high mortality are in the lower Mississippi Valley, upper
      Great Plains, and Mountain West, with additional areas in west Texas, and the
      panhandle of Florida, Significant clusters of low mortality are in the Midwest
      and urbanized Northeast. CONCLUSION: There is no consistent source of hazard
      mortality data, yet improvements in existing databases can produce quality data
      that can be incorporated into spatial epidemiological studies as demonstrated in
      this paper. It is important to view natural hazard mortality through a geographic
      lens so as to better inform the public living in such hazard prone areas, but
      more importantly to inform local emergency practitioners who must plan for and
      respond to disasters in their community.

PMID- 19091057
TI  - Integrase and integration: biochemical activities of HIV-1 integrase.
AB  - Integration of retroviral DNA is an obligatory step of retrovirus replication
      because proviral DNA is the template for productive infection. Integrase, a
      retroviral enzyme, catalyses integration. The process of integration can be
      divided into two sequential reactions. The first one, named 3'-processing,
      corresponds to a specific endonucleolytic reaction which prepares the viral DNA
      extremities to be competent for the subsequent covalent insertion, named strand
      transfer, into the host cell genome by a trans-esterification reaction. Recently,
      a novel specific activity of the full length integrase was reported, in vitro, by
      our group for two retroviral integrases (HIV-1 and PFV-1). This activity of
      internal cleavage occurs at a specific palindromic sequence mimicking the LTR-LTR
      junction described into the 2-LTR circles which are peculiar viral DNA forms
      found during viral infection. Moreover, recent studies demonstrated the existence
      of a weak palindromic consensus found at the integration sites. Taken together,
      these data underline the propensity of retroviral integrases for binding
      symmetrical sequences and give perspectives for targeting specific sequences used
      for gene therapy.

PMID- 19091059
TI  - Role of MAPT mutations and haplotype in frontotemporal lobar degeneration in
      Northern Finland.
AB  - BACKGROUND: Frontotemporal lobar degeneration (FTLD) consists of a clinically and
      neuropathologically heterogeneous group of syndromes affecting the frontal and
      temporal lobes of the brain. Mutations in microtubule-associated protein tau
      (MAPT), progranulin (PGRN) and charged multi-vesicular body protein 2B (CHMP2B)
      are associated with familial forms of the disease. The prevalence of these
      mutations varies between populations. The H1 haplotype of MAPT has been found to
      be closely associated with tauopathies and with sporadic FTLD. Our aim was to
      investigate MAPT mutations and haplotype frequencies in a clinical series of
      patients with FTLD in Northern Finland. METHODS: MAPT exons 1, 2 and 9-13 were
      sequenced in 59 patients with FTLD, and MAPT haplotypes were analysed in these
      patients, 122 patients with early onset Alzheimer's disease (eoAD) and 198
      healthy controls. RESULTS: No pathogenic mutations were found. The H2 allele
      frequency was 11.0% (P = 0.028) in the FTLD patients, 9.8% (P = 0.029) in the
      eoAD patients and 5.3% in the controls. The H2 allele was especially clustered in
      patients with a positive family history (P = 0.011) but did not lower the age at
      onset of the disease. The ApoE4 allele frequency was significantly increased in
      the patients with eoAD and in those with FTLD. CONCLUSION: We conclude that
      although pathogenic MAPT mutations are rare in Northern Finland, the MAPT H2
      allele may be associated with increased risks of FTLD and eoAD in the Finnish
      population.

PMID- 19091061
TI  - The role of coronary artery calcification score in clinical practice.
AB  - BACKGROUND: Coronary artery calcification (CAC) measured by electron-beam
      computed tomography (EBCT) has been well studied in the prediction of coronary
      artery disease (CAD). We sought to evaluate the impact of the CAC score in the
      diagnostic process immediately after its introduction in a large tertiary
      referral centre. METHODS: 598 patients with no history of CAD who underwent EBCT
      for evaluation of CAD were retrospectively included into the study. Ischemia
      detection test results (exercise stress test, single photon emission computed
      tomography or ST segment analysis on 24 hours ECG detection), as well as the
      results of coronary angiography (CAG) were collected. RESULTS: The mean age of
      the patients was 55 +/- 11 years (57% male). Patients were divided according to
      CAC scores; group A < 10, B 10 - 99, C 100 - 399 and D >or= 400 (304, 135, 89 and
      70 patients respectively). Ischemia detection tests were performed in 531 (89%)
      patients; negative ischemia results were found in 362 patients (183 in group A,
      87 in B, 58 in C, 34 in D). Eighty-eight percent of the patients in group D
      underwent CAG despite negative ischemia test results, against 6% in group A, 16%
      in group B and 29% in group C. A positive ischemia test was found in 74 patients
      (25 in group A, 17 in B, 16 in C, 16 in D). In group D 88% (N = 14) of the
      patients with a positive ischemia test were referred for CAG, whereas 38 - 47% in
      group A-C. CONCLUSION: Our study showed that patients with a high CAC score are
      more often referred for CAG. The CAC scores can be used as an aid in daily
      cardiology practice to determine further decision making.

PMID- 19091062
TI  - Herpes simplex I encephalitis presenting as a brain haemorrhage with normal
      cerebrospinal fluid analysis: a case report.
AB  - INTRODUCTION: Herpes simplex encephalitis is a potentially lethal infection that
      should be recognised as soon as possible. The combination of clinical history and
      examination, brain computed tomography or magnetic resonance imaging and lumbar
      puncture has been used to establish a diagnosis. CASE PRESENTATION: We present a
      patient who had a suggestive history but a totally normal lumbar puncture and
      only evidence of intracerebral haemorrhage in the brain magnetic resonance
      imaging. Diagnosis was made by using the cerebrospinal fluid polymerase chain
      reaction for herpes simplex virus. CONCLUSION: Herpes simplex encephalitis is
      being increasingly diagnosed with the availability of new diagnostic techniques.
      Herpes simplex encephalitis can present with the combination of haemorrhage and
      normal cerebrospinal fluid. Awareness of this common but, if left untreated,
      devastating condition should increase.

PMID- 19091060
TI  - Quantitative protein expression profiling reveals extensive post-transcriptional
      regulation and post-translational modifications in schizont-stage malaria
      parasites.
AB  - BACKGROUND: Malaria is a one of the most important infectious diseases and is
      caused by parasitic protozoa of the genus Plasmodium. Previously, quantitative
      characterization of the P. falciparum transcriptome demonstrated that the
      strictly controlled progression of these parasites through their intra
      erythrocytic developmental cycle is accompanied by a continuous cascade of gene
      expression. Although such analyses have proven immensely useful, the correlations
      between abundance of transcripts and their cognate proteins remain poorly
      characterized. RESULTS: Here, we present a quantitative time-course analysis of
      relative protein abundance for schizont-stage parasites (34 to 46 hours after
      invasion) based on two-dimensional differential gel electrophoresis of protein
      samples labeled with fluorescent dyes. For this purpose we analyzed parasite
      samples taken at 4-hour intervals from a tightly synchronized culture and
      established more than 500 individual protein abundance profiles with high
      temporal resolution and quantitative reproducibility. Approximately half of all
      profiles exhibit a significant change in abundance and 12% display an expression
      peak during the observed 12-hour time interval. Intriguingly, identification of
      54 protein spots by mass spectrometry revealed that 58% of the corresponding
      proteins--including actin-I, enolase, eukaryotic initiation factor (eIF)4A,
      eIF5A, and several heat shock proteins--are represented by more than one isoform,
      presumably caused by post-translational modifications, with the various isoforms
      of a given protein frequently showing different expression patterns. Furthermore,
      comparisons with transcriptome data generated from the same parasite samples
      reveal evidence of significant post-transcriptional gene expression regulation.
      CONCLUSIONS: Together, our data indicate that both post-transcriptional and post
      translational events are widespread and of presumably great biological
      significance during the intra-erythrocytic development of P. falciparum.

PMID- 19091063
TI  - Sclerosing mesenteritis affecting the small and the large intestine in a male
      patient with non-Hodgkin lymphoma: a case presentation and review of the
      literature.
AB  - INTRODUCTION: Sclerosing mesenteritis is a rare disease resembling a mesenteric
      tumour. We present here a case of sclerosing mesenteritis that affected both the
      large and the small intestine of the patient. Therapeutic and diagnostic issues
      are discussed. CASE PRESENTATION: A 62-year-old man with a history of non-Hodgkin
      lymphoma presented with fatigue, a palpable tender abdominal mass and clinical
      signs of progressing intestinal obstruction. The preoperative evaluation failed
      to prove recurrence of the lymphoma or any other definite diagnosis. A laparotomy
      was performed through a midline incision. The mesentery resembled a tumour-like
      thickened and fibrotic mass. Abundant, rigid intestinal loop adhesions were
      observed. Diffuse fibrotic infiltration of the ileum and of the sigmoid colon,
      which obviously affected the intestinal vascular supply, were identified. A right
      colectomy and partial sigmoidectomy were performed. Pathological evaluation
      revealed extensive myofibroblastic reaction of the mesentery with accompanying
      loci of fat necrosis and areas of inflammation. A diffuse fibrotic infiltration
      that focally showed a ground-glass appearance was observed. The post-operative
      course was complicated by respiratory insufficiency and infections and the
      patient died 2 months after the operation. CONCLUSION: Sclerosing mesenteritis
      that affects both the small and the large intestine is extremely rare. The
      disease is characterized by myofibroblastic reaction, fat necrosis and diffuse
      fibrosis of the mesentery. Pathological confirmation may be required for definite
      diagnosis. If the disease is characterized by severe and diffuse fibrosis, then
      the application of surgical therapy may be problematic.

PMID- 19091064
TI  - Central retinal artery occlusion and non-arteritic anterior ischemic optic
      neuropathy associated with an overlap syndrome: a case report.
AB  - INTRODUCTION: An "overlap syndrome" is defined as the sequential appearance over
      time of two or more risk factors for glaucomatous damage. The appearance of a new
      risk factor can alter the course and prognosis of previously stable disease.
      Exfoliation syndrome is a leading cause of glaucoma and is associated with
      vascular disease. We report a case of central retinal artery occlusion and non
      arteritic anterior ischemic optic neuropathy in a patient with overlap syndrome.
      CASE PRESENTATION: An 87-year-old woman with longstanding stable primary open
      angle glaucoma developed bilateral exfoliation syndrome, after which her
      intraocular pressure became uncontrolled and her glaucomatous damage progressed
      rapidly. She also developed ischemic arterial events in both eyes. CONCLUSION:
      The case presented here shows that overlap syndromes can lead to rapid,
      irreversible vision impairment. To the best of our knowledge, this is the first
      reported case of central retinal artery occlusion and non-arteritic anterior
      ischemic optic neuropathy in a patient with overlap syndrome.

PMID- 19091065
TI  - Heterotopic pregnancy following ovulation induction by Clomiphene and a healthy
      live birth: a case report.
AB  - INTRODUCTION: A heterotopic pregnancy is defined as the presence of a combined
      intrauterine and ectopic pregnancy. Its estimated incidence is accepted as
      between 1/7000 and 1/30,000 pregnancies. It is also reported to be as high as 1%
      after the use of assisted reproductive technology, but Clomiphene Citrate which
      increases the rate of twinning, could be associated with a heterotopic pregnancy
      rate of 1/900, which is much less than using assisted reproductive technology.
      Heterotopic pregnancies are diagnostic and therapeutic challenges for
      obstetricians. If they continue without diagnosis, a life-threatening situation
      may occur even when surgical intervention with laparotomy is performed. CASE
      PRESENTATION: We present the case of a 22-year-old Iranian woman who developed a
      simultaneous extra -and intrauterine pregnancy after the induction of ovulation
      with Clomiphene. In this case, there was a delay in the detection of the ectopic
      pregnancy component resulting in an emergency laparotomy being performed.
      Fortunately after the laparotomy, the intrauterine pregnancy was not affected and
      it progressed satisfactorily until 37 weeks. A healthy male baby was delivered by
      caesarean section. CONCLUSION: This case suggests that a heterotopic pregnancy
      must always be considered in patients presenting with pelvic pain even in a
      confirmed intrauterine pregnancy, particularly after the induction of ovulation
      by Clomiphene Citrate or assisted reproductive technology. Every clinician
      treating women of reproductive age should keep this diagnosis in mind. It also
      demonstrates that early diagnosis is essential in order to salvage the
      intrauterine pregnancy and avoid maternal morbidity and mortality.

PMID- 19091066
TI  - New paradigms in cervical cancer prevention: opportunities and risks.
AB  - Testing for the DNA of high-risk types of papilloma virus (HPV) is more sensitive
      than cytology in detecting pre-cancerous lesions. One of the main advantages will
      be the possibility of applying prolonged screening intervals. However adequate
      screening protocols (age of start and stop, screening intervals, management of
      HPV positive women) need to be applied in order to avoid over-referral to
      colposcopy and over-treatment and to maintain sustainable costs. Further follow
      up of running trials and research on molecular markers will better define these
      parameters. The new situation will require organised screening programmes with
      rigorous protocols and monitoring. This will be even more needed when women
      vaccinated for HPV 16 and 18 will be screened. Research on how to best screen
      vaccinated women is a priority. This paper proposes an overview of the plausible
      impact of new technologies in cervical cancer screening in the near future and in
      the vaccinated cohorts.

PMID- 19091067
TI  - A report of the Sixth Annual Meeting of the International Society for the
      Prevention of Tobacco Induced Diseases (ISPTID).
AB  - The Sixth meeting of the International Society for the Prevention of Tobacco
      Induced Diseases (ISPTiD) was held in Little Rock, Arkansas on November 2-4, 2007
      and has brought together 140 participants, scientists and experts in this
      specialized field from 30 countries across the World. The central theme of the
      conference was the "Translational Approaches to the Prevention of Tobacco Induced
      Diseases". Discussions held during the three days meeting's sessions (including
      poster session and platform discussion) promoted a better understanding of the
      connection between tobacco use and associated medical and health consequences.
      The Sixth Annual meeting of ISPTiD served as another successful step toward
      decrease in the huge sociological and economical burden that the entire World is
      facing with this addiction. The proceedings of the meeting were published in the
      conference booklet, the ISPTiD global web site and Cancer Database abstract web
      site. Funds generated from this meeting helped in part to establish the society's
      Journal "Tobacco Induced Diseases "into the major scientific journal index PubMed
      database and BioMed Central. The meeting set the tone for next the Annual meeting
      in Kyoto, Japan for the year 2008 with the theme "Tobacco free future".

PMID- 19091068
TI  - Vitamin C in plasma is inversely related to blood pressure and change in blood
      pressure during the previous year in young Black and White women.
AB  - BACKGROUND: The prevalence of hypertension and its contribution to cardiovascular
      disease risk makes it imperative to identify factors that may help prevent this
      disorder. Extensive biological and biochemical data suggest that plasma ascorbic
      acid may be such a factor. In this study we examined the association between
      plasma ascorbic acid concentration and blood pressure (BP) in young-adult women.
      METHODS: Participants were 242 Black and White women aged 18-21 yr from the
      Richmond, CA, cohort of the National Heart, Lung and Blood Institute Growth and
      Health Study. We examined the associations of plasma ascorbic acid with BP at
      follow-up year 10, and with change in BP during the previous year. RESULTS: In
      cross-sectional analysis, plasma ascorbic acid at year 10 was inversely
      associated with systolic BP and diastolic BP after adjusting for race, body mass
      index, education, and dietary intake of fat and sodium. Persons in the highest
      one-fourth of the plasma ascorbic acid distribution had 4.66 mmHg lower systolic
      BP (95% CI 1.10 to 8.22 mmHg, p = 0.005) and 6.04 mmHg lower diastolic BP (95% CI
      2.70 to 9.38 mmHg, p = 0.0002) than those in the lowest one-fourth of the
      distribution. In analysis of the change in BP, plasma ascorbic acid was also
      inversely associated with change in systolic BP and diastolic BP during the
      previous year. While diastolic blood pressure among persons in the lowest
      quartile of plasma ascorbic acid increased by 5.97 mmHg (95% CI 3.82 to 8.13
      mmHg) from year 9 to year 10, those in the highest quartile of plasma vitamin C
      increased by only 0.23 mmHg (95% CI -1.90 to +2.36 mmHg) (test for linear trend:
      p < 0.0001). A similar effect was seen for change in systolic BP, p = 0.005.
      CONCLUSION: Plasma ascorbic acid was found to be inversely associated with BP and
      change in BP during the prior year. The findings suggest the possibility that
      vitamin C may influence BP in healthy young adults. Since lower BP in young
      adulthood may lead to lower BP and decreased incidence of age-associated vascular
      events in older adults, further investigation of treatment effects of vitamin C
      on BP regulation in young adults is warranted.

PMID- 19091069
TI  - Incidence, organ dysfunction and mortality in severe sepsis: a Spanish
      multicentre study.
AB  - INTRODUCTION: Sepsis is a leading cause of admission to non-cardiological
      intensive care units (ICUs) and the second leading cause of death among ICU
      patients. We present the first extensive dataset on the epidemiology of severe
      sepsis treated in ICUs in Spain. METHODS: We conducted a prospective,
      observational, multicentre cohort study, carried out over two 3-month periods in
      2002. Our aims were to determine the incidence of severe sepsis among adults in
      ICUs in a specific area in Spain, to determine the early (48 h) ICU and hospital
      mortality rates, as well as factors associated with the risk of death. RESULTS: A
      total of 4,317 patients were admitted and 2,619 patients were eligible for the
      study; 311 (11.9%) of these presented at least 1 episode of severe sepsis, and
      324 (12.4%) episodes of severe sepsis were recorded. The estimated accumulated
      incidence for the population was 25 cases of severe sepsis attended in ICUs per
      100,000 inhabitants per year. The mean logistic organ dysfunction system (LODS)
      upon admission was 6.3; the mean sepsis-related organ failure assessment (SOFA)
      score on the first day was 9.6. Two or more organ failures were present at
      diagnosis in 78.1% of the patients. A microbiological diagnosis of the infection
      was reached in 209 episodes of sepsis (64.5%) and the most common clinical
      diagnosis was pneumonia (42.8%). A total of 169 patients (54.3%) died in
      hospital, 150 (48.2%) of these in the ICU. The mortality in the first 48 h was
      14.8%. Factors associated with early death were haematological failure and liver
      failure at diagnosis, acquisition of the infection prior to ICU admission, and
      total LODS score on admission. Factors associated with death in the hospital were
      age, chronic alcohol abuse, increased McCabe score, higher LODS on admission,
      DeltaSOFA 3-1 (defined as the difference in the total SOFA scores on day 3 and on
      day 1), and the difference of the area under the curve of the SOFA score
      throughout the first 15 days. CONCLUSIONS: We found a high incidence of severe
      sepsis attended in the ICU and high ICU and hospital mortality rates. The high
      prevalence of multiple organ failure at diagnosis and the high mortality in the
      first 48 h suggests delays in diagnosis, in initial resuscitation, and/or in
      initiating appropriate antibiotic treatment.

PMID- 19091070
TI  - Insulin-like growth factor I promotes cord blood T cell maturation through
      monocytes and inhibits their apoptosis in part through interleukin-6.
AB  - BACKGROUND: The functional immaturity of T cells contributes to the
      susceptibility of neonates to infections and the less severe graft-versus-host
      disease associated with cord blood (CB) transplantation. We have previously
      reported that insulin-like growth factor - I (IGF-I) promotes the
      phytohaemagglutinin (PHA)-induced CB T cell maturation and inhibits their
      apoptosis in mononuclear cell (MC) culture. We hypothesized that the effects of
      IGF-I may be mediated by accessory cells and soluble factors. RESULTS: This study
      showed that the kinetics of PHA-induced maturation in purified CD3+ T cell was
      delayed compared to that in CBMC. The addition of autologous CD14+ monocytes
      increased T cell maturation and potentiated the effect of IGF-I. The addition of
      IL-6 had no effect on CB T cell maturation but it reduced PHA-induced apoptosis
      significantly. We further demonstrated that the neutralisation of IL-6 in CBMC
      culture partially abrogated the anti-apoptotic effect of IGF-1 on T cells. The
      anti-apoptotic effect of IL-6 was not mediated via the reduction of Fas
      expression in T cell subsets. CONCLUSION: Our results suggested that the
      maturation effect of IGF-1 is partially mediated by monocytes and the anti
      apoptotic effect in part via IL-6. Further investigation is needed to explore the
      therapeutic use of IGF-I in enhancing neonatal immunity.

PMID- 19091071
TI  - Signal duration and the time scale dependence of signal integration in
      biochemical pathways.
AB  - BACKGROUND: Signal duration (e.g. the time over which an active signaling
      intermediate persists) is a key regulator of biological decisions in myriad
      contexts such as cell growth, proliferation, and developmental lineage
      commitments. Accompanying differences in signal duration are numerous downstream
      biological processes that require multiple steps of biochemical regulation.
      RESULTS: Here we present an analysis that investigates how simple biochemical
      motifs that involve multiple stages of regulation can be constructed to
      differentially process signals that persist at different time scales. We compute
      the dynamic, frequency dependent gain within these networks and resulting power
      spectra to better understand how biochemical networks can integrate signals at
      different time scales. We identify topological features of these networks that
      allow for different frequency dependent signal processing properties. CONCLUSION:
      We show that multi-staged cascades are effective in integrating signals of long
      duration whereas multi-staged cascades that operate in the presence of negative
      feedback are effective in integrating signals of short duration. Our studies
      suggest principles for why signal duration in connection with multiple steps of
      downstream regulation is a ubiquitous motif in biochemical systems.

PMID- 19091072
TI  - PocketMatch: a new algorithm to compare binding sites in protein structures.
AB  - BACKGROUND: Recognizing similarities and deriving relationships among protein
      molecules is a fundamental requirement in present-day biology. Similarities can
      be present at various levels which can be detected through comparison of protein
      sequences or their structural folds. In some cases similarities obscure at these
      levels could be present merely in the substructures at their binding sites.
      Inferring functional similarities between protein molecules by comparing their
      binding sites is still largely exploratory and not as yet a routine protocol. One
      of the main reasons for this is the limitation in the choice of appropriate
      analytical tools that can compare binding sites with high sensitivity. To benefit
      from the enormous amount of structural data that is being rapidly accumulated, it
      is essential to have high throughput tools that enable large scale binding site
      comparison. RESULTS: Here we present a new algorithm PocketMatch for comparison
      of binding sites in a frame invariant manner. Each binding site is represented by
      90 lists of sorted distances capturing shape and chemical nature of the site. The
      sorted arrays are then aligned using an incremental alignment method and scored
      to obtain PMScores for pairs of sites. A comprehensive sensitivity analysis and
      an extensive validation of the algorithm have been carried out. A comparison with
      other site matching algorithms is also presented. Perturbation studies where the
      geometry of a given site was retained but the residue types were changed
      randomly, indicated that chance similarities were virtually non-existent. Our
      analysis also demonstrates that shape information alone is insufficient to
      discriminate between diverse binding sites, unless combined with chemical nature
      of amino acids. CONCLUSION: A new algorithm has been developed to compare binding
      sites in accurate, efficient and high-throughput manner. Though the
      representation used is conceptually simplistic, we demonstrate that along with
      the new alignment strategy used, it is sufficient to enable binding comparison
      with high sensitivity. Novel methodology has also been presented for validating
      the algorithm for accuracy and sensitivity with respect to geometry and chemical
      nature of the site. The method is also fast and takes about 1/250th second for
      one comparison on a single processor. A parallel version on BlueGene has also
      been implemented.

PMID- 19091073
TI  - An analysis of the subtypes of dengue fever infections in Barbados 2003-2007 by
      reverse transcriptase polymerase chain reaction.
AB  - BACKGROUND: To perform a retrospective analysis of patients with IgM antibodies
      to dengue fever infection to determine the serotypes present by molecular
      techniques. A representative sample (approximately 20%/per year) of patients
      diagnosed with dengue fever infection were selected based on the detection of IgM
      antibodies in the acute phase serum sample. RNA was extracted from each sample
      and reverse transcribed. Following this, the amplicons were electrophoresed and
      serotyped based on band sizes. RESULTS: This study consisted of 71 males and 101
      females ranging in age from 0 - 50+ yrs giving a total of 172 persons with an
      average of 34.4 patients per year. Onset averaged 6.9 days ranging from 0-90
      days. Common symptoms were as follows: fever (69%), headache (52%), arthralgia
      (36%), ocular pain (32%), emesis (15%) and lumbar pain (15%). All patients
      investigated with the exception of one, were infected with DENV-3. CONCLUSION:
      DENV-3 is currently circulating on the island and not DENV-1 or DENV-2 as in
      previous years. This has implications for the enhancement of clinical, laboratory
      and environmental surveillance systems.

PMID- 19091074
TI  - Transcriptome profiling of the feeding-to-fasting transition in chicken liver.
AB  - BACKGROUND: Starvation triggers a complex array of adaptative metabolic responses
      including energy-metabolic responses, a process which must imply tissue specific
      alterations in gene expression and in which the liver plays a central role. The
      present study aimed to describe the evolution of global gene expression profiles
      in liver of 4-week-old male chickens during a 48 h fasting period using a chicken
      20 K oligoarray. RESULTS: A large number of genes were modulated by fasting (3532
      genes with a pvalue corrected by Benjamini-Hochberg < 0.01); 2062 showed an
      amplitude of variation higher than +/- 40% among those, 1162 presented an human
      ortholog, allowing to collect functional information. Notably more genes were
      down-regulated than up-regulated, whatever the duration of fasting (16 h or 48
      h). The number of genes differentially expressed after 48 h of fasting was 3.5
      fold higher than after 16 h of fasting. Four clusters of co-expressed genes were
      identified by a hierarchical cluster analysis. Gene Ontology, KEGG and Ingenuity
      databases were then used to identify the metabolic processes associated to each
      cluster. After 16 h of fasting, genes involved in ketogenesis, gluconeogenesis
      and mitochondrial or peroxisomal fatty acid beta-oxidation, were up-regulated
      (cluster-1) whereas genes involved in fatty acid and cholesterol synthesis were
      down-regulated (cluster-2). For all genes tested, the microarray data was
      confirmed by quantitative RT-PCR. Most genes were altered by fasting as already
      reported in mammals. A notable exception was the HMG-CoA synthase 1 gene, which
      was up-regulated following 16 and 48 h of fasting while the other genes involved
      in cholesterol metabolism were down-regulated as reported in mammalian studies.
      We further focused on genes not represented on the microarray and candidates for
      the regulation of the target genes belonging to cluster-1 and -2 and involved in
      lipid metabolism. Data are provided concerning PPARa, SREBP1, SREBP2, NR1H3
      transcription factors and two desaturases (FADS1, FADS2). CONCLUSION: This study
      evidences numerous genes altered by starvation in chickens and suggests a global
      repression of cellular activity in response to this stressor. The central role of
      lipid and acetyl-CoA metabolisms and its regulation at transcriptional level are
      confirmed in chicken liver in response to short-term fasting. Interesting
      expression modulations were observed for NR1H3, FADS1 and FADS2 genes. Further
      studies are needed to precise their role in the complex regulatory network
      controlling lipid metabolism.

PMID- 19091075
TI  - Expressed breast milk as 'connection' and its influence on the construction of
      'motherhood' for mothers of preterm infants: a qualitative study.
AB  - BACKGROUND: Breast milk is considered the optimal nutrition for all newborn
      infants. While there is high initiation of lactation among mothers of preterm
      infants in Australia, there is a rapid decline of continued lactation.
      Furthermore, there is an inverse relationship between infant gestation and
      duration of lactation. To better understand the breastfeeding experience of
      parents of very low birth weight (VLBW) preterm infants an interpretive
      phenomenological study was conducted. METHODS: This longitudinal study was
      conducted using an interpretive phenomenological approach. Data were collected
      from 17 parents through 45 individual interviews with both mothers and fathers,
      from birth to 12 months of age. This data was then transcribed verbatim and
      analysed using thematic analysis. RESULTS: The analysis identified six primary
      themes: the intention to breastfeed naturally; breast milk as connection; the
      maternal role of breast milk producer; breast milk as the object of attention;
      breastfeeding and parenting the hospitalised baby and the demise of
      breastfeeding. This paper reports on the theme of 'breast milk as
      connection'.Providing expressed breast milk offered one way the mothers could be
      physiologically and emotionally connected to their preterm infant while they were
      in the constant care of hospital staff. Indeed, breast milk was considered the
      only way the new mother could connect her body (or part there of) to her preterm
      baby in hospital. This sense of connection however, comes at a cost. On the one
      hand, the breast milk offers a feeling of connection to the baby, but, on the
      other, this connection comes only after disconnection of the mother and baby and 
      through breast expression - mother and her milk. This ability of breast milk to
      connect mother and baby makes the expressed breast milk highly valued, and places
      unexpected pressure on the mother to produce milk as integral to her sense of
      motherhood. CONCLUSION: The findings of this study have implications for
      healthcare practice. It is evident that the association of breastfeeding success
      with mothering success only jeopardises some families' self-esteem and sense of
      parenting ability. These findings suggest it would be beneficial to find
      alternate ways to connect preterm infants and their parents in the preterm
      nursery environment, and find more positive ways to support breastfeeding.

PMID- 19091076
TI  - Phenotypic and molecular characterisation of Brucella isolates from marine
      mammals.
AB  - BACKGROUND: Bacteria of the genus Brucella are the causative organisms of
      brucellosis in animals and man. Previous characterisation of Brucella strains
      originating from marine mammals showed them to be distinct from the terrestrial
      species and likely to comprise one or more new taxa. Recently two new species
      comprising Brucella isolates from marine mammals, B. pinnipedialis and B. ceti,
      were validly published. Here we report on an extensive study of the molecular and
      phenotypic characteristics of marine mammal Brucella isolates and on how these
      characteristics relate to the newly described species. RESULTS: In this study,
      102 isolates of Brucella originating from eleven species of marine mammals were
      characterised. Results obtained by analysis using the Infrequent Restriction Site
      (IRS)-Derivative PCR, PCR-RFLP of outer membrane protein genes (omp) and IS711
      fingerprint profiles showed good consistency with isolates originating from
      cetaceans, corresponding to B. ceti, falling into two clusters. These correspond
      to isolates with either dolphins or porpoises as their preferred host. Isolates
      originating predominantly from seals, and corresponding to B. pinnipedialis,
      cluster separately on the basis of IS711 fingerprinting and other molecular
      approaches and can be further subdivided, with isolates from hooded seals
      comprising a distinct group. There was little correlation between phenotypic
      characteristics used in classical Brucella biotyping and these groups.
      CONCLUSION: Molecular approaches are clearly valuable in the division of marine
      mammal Brucella into subtypes that correlate with apparent ecological divisions,
      whereas conventional bioyping is of less value. The data presented here confirm
      that there are significant subtypes within the newly described marine mammal
      Brucella species and add to a body of evidence that could lead to the recognition
      of additional species or sub-species within this group.

PMID- 19091077
TI  - Effect of combined treatment with alendronate and calcitriol on femoral neck
      strength in osteopenic rats.
AB  - BACKGROUND: Hip fracture is associated with pronounced morbidity and excess
      mortality in elderly women with postmenopausal osteoporosis. Many drugs have been
      developed to treat osteoporosis and to reduce the risk of osteoporotic fractures.
      We investigated the effects of combined alendronate and vitamin D3 treatment on
      bone mass and fracture load at the femoral neck in ovariectomized (OVX) rats, and
      evaluated the relationship between bone mass parameters and femoral neck
      strength. METHODS: Thirty 12-week-old female rats underwent either a sham
      operation (n = 6) or OVX (n = 24). Twenty weeks later, OVX rats were further
      divided into four groups and received daily doses of either saline alone, 0.1
      mg/kg alendronate, 0.1 microg/kg calcitriol, or a combination of both two drugs
      by continuous infusion via Alzet mini-osmotic pumps. The sham-control group
      received saline alone. After 12 weeks of treatment, femoral necks were examined
      using peripheral quantitative computed tomography (pQCT) densitometry and
      mechanical testing. RESULTS: Saline-treated OVX rats showed significant decreases
      in total bone mineral content (BMC) (by 28.1%), total bone mineral density (BMD)
      (by 9.5%), cortical BMC (by 26.3%), cancellous BMC (by 66.3%), cancellous BMD (by
      29.0%) and total cross-sectional bone area (by 30.4%) compared with the sham
      control group. The combined alendronate and calcitriol treatments improved bone
      loss owing to estrogen deficiency. On mechanical testing, although OVX
      significantly reduced bone strength of the femoral neck (by 29.3%) compared with
      the sham-control group, only the combined treatment significantly improved the
      fracture load at the femoral neck in OVX rats to the level of the sham-controls.
      The correlation of total BMC to fracture load was significant, but that of total
      BMD was not. CONCLUSION: Our results showed that the combined treatment with
      alendronate and calcitriol significantly improved bone fragility of the femoral
      neck in OVX osteopenic rats.

PMID- 19091078
TI  - Towards a Formative Assessment of Classroom Competencies (FACCs) for postgraduate
      medical trainees.
AB  - BACKGROUND: An assumption of clinical competency is no longer acceptable or
      feasible in routine clinical practice. We sought to determine the feasibility,
      practicability and efficacy of undertaking a formal assessment of clinical
      competency for all postgraduate medical trainees in a large NHS foundation trust.
      METHODS: FY1 doctors were asked to complete a questionnaire to determine prior
      experience and self reported confidence in performing the GMC core competencies.
      From this a consensus panel of key partners considered and developed an 8 station
      Objective Structured Clinical Examination (OSCE) circuit to assess clinical
      competencies in all training grade medical staff... The OSCE was then
      administered to all training grade doctors as part of their NHS trust induction
      process. RESULTS: 106 (87.6% of all trainees) participated in the assessment
      during the first 14 days of appointment. Candidates achieved high median raw
      percentage scores for the majority of stations however analysis of pre defined
      critical errors and omissions identified important areas for concern. Performance
      of newly qualified FY1 doctor was significantly better than other grades for the
      arterial blood gas estimation and nasogastric tube insertion stations.
      DISCUSSION: Delivering a formal classroom assessment of clinical competencies to
      all trainees as part of the induction process was both feasible and useful. The
      assessment identified areas of concern for future training and also served to
      reassure as to the proficiency of trainees in undertaking the majority of core
      competencies.

PMID- 19091079
TI  - Response of the cytoplasmic and membrane proteome of Corynebacterium glutamicum
      ATCC 13032 to pH changes.
AB  - BACKGROUND: C. glutamicum has traditionally been grown in neutral-pH media for
      amino acid production, but in a previous article we reported that this
      microorganism is a moderate alkaliphile since it grows optimally at pH 7.0-9.0,
      as shown in fermentor studies under tightly controlled pH conditions. We
      determined the best pH values to study differential expression of several genes
      after acidic or basic pH conditions (pH 6.0 for acidic expression and pH 9.0 for
      alkaline expression). Thus, it was interesting to perform a detailed analysis of
      the pH-adaptation response of the proteome of C. glutamicum ATCC 13032 to clarify
      the circuits involved in stress responses in this bacterium. In this paper we
      used the above indicated pH conditions, based on transcriptional studies, to
      confirm that pH adaptation results in significant changes in cytoplasmatic and
      membrane proteins. RESULTS: The cytoplasmatic and membrane proteome of
      Corynebacterium glutamicum ATCC 13032 at different pH conditions (6.0, 7.0 and
      9.0) was analyzed by classical 2D-electrophoresis, and by anion exchange
      chromatography followed by SDS-PAGE (AIEC/SDS-PAGE). A few cytoplasmatic proteins
      showed differential expression at the three pH values with the classical 2D
      technique including a hypothetical protein cg2797, L-2.3-butanediol dehydrogenase
      (ButA), and catalase (KatA). The AIEC/SDS-PAGE technique revealed several
      membrane proteins that respond to pH changes, including the succinate
      dehydrogenase complex (SdhABCD), F0F1-ATP synthase complex subunits b, alpha and
      delta (AtpF, AtpH and AtpA), the nitrate reductase II alpha subunit (NarG), and a
      hypothetical secreted/membrane protein cg0752. Induction of the F0F1-ATP synthase
      complex beta subunit (AtpD) at pH 9.0 was evidenced by Western analysis. By
      contrast, L-2.3-butanediol dehydrogenase (ButA), an ATPase with chaperone
      activity, the ATP-binding subunit (ClpC) of an ATP-dependent protease complex, a
      7 TMHs hypothetical protein cg0896, a conserved hypothetical protein cg1556, and
      the dihydrolipoamide acyltransferase SucB, were clearly up-regulated at pH 6.0.
      CONCLUSION: The observed protein changes explain the effect of the extracellular
      pH on the growth and physiology of C. glutamicum. Some of the proteins up
      regulated at alkaline pH respond also to other stress factors suggesting that
      they serve to integrate the cell response to different stressing conditions.

PMID- 19091080
TI  - Phosphodiesterase 4 inhibition but not beta-adrenergic stimulation suppresses
      tumor necrosis factor-alpha release in peripheral blood mononuclear cells in
      septic shock.
AB  - INTRODUCTION: Stimulation of beta2-adrenergic receptors (beta2-ARs) inhibits
      tumor necrosis factor-alpha (TNF-alpha) release in monocytes. In septic shock,
      endogenous catecholamines induce beta2-AR downregulation, leading to an increased
      TNF-alpha release. The aims of this study were to analyze the molecular
      mechanisms of beta-adrenergic downregulation and to explore therapeutic
      interventions with maintained anti-inflammatory efficacy in septic shock using
      the inhibition of phosphodiesterase 4 (PDE4). METHODS: We conducted in vitro
      stimulation of peripheral blood mononuclear cells of healthy volunteers (n = 20)
      and patients with septic shock (n = 20) with lipopolysaccharide (LPS) or
      Staphylococcus aureus enterotoxin B (SEB) without or with isoprenaline, forskolin
      (an activator of adenylate cyclase), or ropipram (an inhibitor of PDE4). We also
      conducted flow cytometric analysis of Toll-like receptor (TLR) 4 and TLR2 surface
      expression and intracellular TNF-alpha production of untreated and stimulated
      CD14+ monocytes. Protein expression of beta-ARs, of G proteins, of adenylate
      cyclase, and of TLRs was measured by Western blotting. RESULTS: Investigations
      were done by LPS (100 ng/mL) or SEB (10 ng/mL) when TLR4 and TLR2 were maximally
      expressed. LPS- or SEB-treated CD14+ monocytes of healthy volunteers were able to
      produce TNF-alpha. This effect was attenuated by isoprenaline, forskolin, or
      rolipram in a concentration-dependent manner. In CD14+ monocytes of patients with
      septic shock, the anti-inflammatory effect of isoprenaline was completely blunted
      whereas efficacy of forskolin and rolipram was maintained. CD14+ monocytes of
      healthy volunteers were compared with patients with septic shock: protein
      expression of beta2-ARs was reduced and inhibitory G protein was increased,
      whereas no changes in adenylate cyclase and stimulatory G protein were found.
      CONCLUSIONS: In septic shock, the anti-inflammatory effects of catecholamines are
      blunted by downregulation of beta2-ARs and upregulation of the inhibitory G
      protein in CD14+ monocytes. Beta-adrenergic downregulation is overcome by
      inhibitors of PDE4. These results provide a mechanistic rationale for the
      therapeutic use of selective PDE4 inhibitors in the treatment of septic shock.

PMID- 19091081
TI  - AnEnPi: identification and annotation of analogous enzymes.
AB  - BACKGROUND: Enzymes are responsible for the catalysis of the biochemical
      reactions in metabolic pathways. Analogous enzymes are able to catalyze the same
      reactions, but they present no significant sequence similarity at the primary
      level, and possibly different tertiary structures as well. They are thought to
      have arisen as the result of independent evolutionary events. A detailed study of
      analogous enzymes may reveal new catalytic mechanisms, add information about the
      origin and evolution of biochemical pathways and disclose potential targets for
      drug development. RESULTS: In this work, we have constructed and implemented a
      new approach, AnEnPi (the Analogous Enzyme Pipeline), using a combination of
      bioinformatics tools like BLAST, HMMer, and in-house scripts, to assist in the
      identification, annotation, comparison and study of analogous and homologous
      enzymes. The algorithm for the detection of analogy is based i) on the
      construction of groups of homologous enzymes and ii) on the identification of
      cases where a given enzymatic activity is performed by two or more proteins
      without significant similarity between their primary structures. We applied this
      approach to a dataset obtained from KEGG Comprising all annotated enzymes, which
      resulted in the identification of 986 EC classes where putative analogy was
      detected (40.5% of all EC classes). AnEnPi is of considerable value in the
      construction of initial datasets that can be further curated, particularly in
      gene and genome annotation, in studies involving molecular evolution and
      metabolism and in the identification of new potential drug targets. CONCLUSION:
      AnEnPi is an efficient tool for detection and annotation of analogous enzymes and
      other enzymes in whole genomes. It is available for academic use at:
      http://bioinfo.pdtis.fiocruz.br/AnEnPi/

PMID- 19091082
TI  - Development and evaluation of a real-time one step reverse-transcriptase PCR for
      quantitation of Chandipura virus.
AB  - BACKGROUND: Chandipura virus (CHPV), a member of family Rhabdoviridae was
      attributed to an explosive outbreak of acute encephalitis in children in Andhra
      Pradesh, India in 2003 and a small outbreak among tribal children from Gujarat,
      Western India in 2004. The case-fatality rate ranged from 55-75%. Considering the
      rapid progression of the disease and high mortality, a highly sensitive method
      for quantifying CHPV RNA by real-time one step reverse transcriptase PCR (real
      time one step RT-PCR) using TaqMan technology was developed for rapid diagnosis.
      METHODS: Primers and probe for P gene were designed and used to standardize real
      time one step RT-PCR assay for CHPV RNA quantitation. Standard RNA was prepared
      by PCR amplification, TA cloning and run off transcription. The optimized real
      time one step RT-PCR assay was compared with the diagnostic nested RT-PCR and
      different virus isolation systems [in vivo (mice) in ovo (eggs), in vitro (Vero
      E6, PS, RD and Sand fly cell line)] for the detection of CHPV. Sensitivity and
      specificity of real-time one step RT-PCR assay was evaluated with diagnostic
      nested RT-PCR, which is considered as a gold standard. RESULTS: Real-time one
      step RT-PCR was optimized using in vitro transcribed (IVT) RNA. Standard curve
      showed linear relationship for wide range of 102-1010 (r2 = 0.99) with maximum
      Coefficient of variation (CV = 5.91%) for IVT RNA. The newly developed real-time
      RT-PCR was at par with nested RT-PCR in sensitivity and superior to cell lines
      and other living systems (embryonated eggs and infant mice) used for the
      isolation of the virus. Detection limit of real-time one step RT-PCR and nested
      RT-PCR was found to be 1.2 x 100 PFU/ml. RD cells, sand fly cells, infant mice,
      and embryonated eggs showed almost equal sensitivity (1.2 x 102 PFU/ml). Vero and
      PS cell-lines (1.2 x 103 PFU/ml) were least sensitive to CHPV infection.
      Specificity of the assay was found to be 100% when RNA from other viruses or
      healthy individual was used. CONCLUSION: On account of the high sensitivity,
      reproducibility and specificity, the assay can be used for the rapid detection
      and quantitation of CHPV RNA from clinical samples during epidemics and from
      endemic areas. The assay may also find application in screening of antiviral
      compounds, understanding of pathogenesis as well as evaluation of vaccine.

PMID- 19091083
TI  - Translating research into maternal health care policy: a qualitative case study
      of the use of evidence in policies for the treatment of eclampsia and pre
      eclampsia in South Africa.
AB  - BACKGROUND: Few empirical studies of research utilisation have been conducted in
      low and middle income countries. This paper explores how research information, in
      particular findings from randomised controlled trials and systematic reviews,
      informed policy making and clinical guideline development for the use of
      magnesium sulphate in the treatment of eclampsia and pre-eclampsia in South
      Africa. METHODS: A qualitative case-study approach was used to examine the policy
      process. This included a literature review, a policy document review, a timeline
      of key events and the collection and analysis of 15 interviews with policy makers
      and academic clinicians involved in these policy processes and sampled using a
      purposive approach. The data was analysed thematically and explored theoretically
      through the literature on agenda setting and the policy making process. RESULTS:
      Prior to 1994 there was no national maternal care policy in South Africa.
      Consequently each tertiary level institution developed its own care guidelines
      and these recommended a range of approaches to the management of pre-eclampsia
      and eclampsia. The subsequent emergence of new national policies for maternal
      care, including for the treatment of pre-eclampsia and eclampsia, was informed by
      evidence from randomised controlled trials and systematic reviews. This outcome
      was influenced by a number of factors. The change to a democratic government in
      the mid 1990s, and the health reforms that followed, created opportunities for
      maternal health care policy development. The new government was open to academic
      involvement in policy making and recruited academics from local networks into key
      policy making positions in the National Department of Health. The local academic
      obstetric network, which placed high value on evidence-based practice, brought
      these values into the policy process and was also linked strongly to
      international evidence based medicine networks. Within this context of openness
      to policy development, local researchers acted as policy entrepreneurs, bringing
      attention to priority health issues, and to the use of research evidence in
      addressing these. This resulted in the new national maternity care guidelines
      being informed by evidence from randomised controlled trials and recommending
      explicitly the use of magnesium sulphate for the management of eclampsia.
      CONCLUSION: Networks of researchers were important not only in using research
      information to shape policy but also in placing issues on the policy agenda. A
      policy context which created a window of opportunity for new research-informed
      policy development was also crucial.

PMID- 19091084
TI  - Evaluation of the reliability and validity of the Medical Outcomes Study sleep
      scale in patients with painful diabetic peripheral neuropathy during an
      international clinical trial.
AB  - BACKGROUND: Sleep is an important element of functioning and well-being. The
      Medical Outcomes Study Sleep Scale (MOS-Sleep) includes 12 items assessing sleep
      disturbance, sleep adequacy, somnolence, quantity of sleep, snoring, and
      awakening short of breath or with a headache. A sleep problems index, grouping
      items from each of the former domains, is also available. This study evaluates
      the psychometric properties of MOS-Sleep Scale in a painful diabetic peripheral
      neuropathic population based on a clinical trial conducted in six countries.
      METHODS: Clinical data and health-related quality of life data were collected at
      baseline and after 12 weeks of follow-up. Overall, 396 patients were included in
      the analysis. Psychometric properties of the MOS-Sleep were assessed in the
      overall population and per country when the sample size was sufficient. Internal
      consistency reliability was assessed by Cronbach's alpha; the structure of the
      instrument was assessed by verifying item convergent and discriminant criteria;
      construct validity was evaluated by examining the relationships between MOS-Sleep
      scores and sleep interference and pain scores, and SF-36 scores; effect-sizes
      were used to assess the MOS-Sleep responsiveness. The study was conducted in
      compliance with United States Food and Drug Administration regulations for
      informed consent and protection of patient rights. RESULTS: Cronbach's alpha
      ranged from 0.71 to 0.81 for the multi-item dimensions and the sleep problems
      index. Item convergent and discriminant criteria were satisfied with item-scale
      correlations for hypothesized dimensions higher than 0.40 and tending to exceed
      the correlations of items with other dimensions, respectively. Taken
      individually, German, Polish and English language versions had good internal
      consistency reliability and dimension structure. Construct validity was supported
      with lower sleep adequacy score and greater sleep problems index scores
      associated with measures of sleep interference and pain scores. In addition,
      correlations between the SF-36 scores and the MOS-Sleep scores were low to
      moderate, ranging from -0.28 to -0.53. Responsiveness was supported by effect
      sizes > 0.80 for patients who improved according to the mean sleep interference
      and pain scores and clinician and patient global impression of change (p <
      0.0001). CONCLUSION: The MOS-Sleep had good psychometric properties in this
      painful diabetic peripheral neuropathic population. TRIAL REGISTRATION: As this
      study was conducted from 2000 to 2002 (i.e., before the filing requirement came
      out), no trial registration number is available.

PMID- 19091086
TI  - Characterization of deposits formed on diesel injectors in field test and from
      thermal oxidative degradation of n-hexadecane in a laboratory reactor.
AB  - Solid deposits from commercially available high-pressure diesel injectors (HPDI)
      were analyzed to study the solid deposition from diesel fuel during engine
      operation. The structural and chemical properties of injector deposits were
      compared to those formed from the thermal oxidative stressing of a diesel fuel
      range model compound, n-hexadecane at 160 degrees C and 450 psi for 2.5 h in a
      flow reactor. Both deposits consist of polyaromatic compounds (PAH) with oxygen
      moieties. The similarities in structure and composition of the injector deposits
      and n-hexadecane deposits suggest that laboratory experiments can simulate
      thermal oxidative degradation of diesel in commercial injectors. The formation of
      PAH from n-hexadecane showed that aromatization of straight chain alkanes and
      polycondensation of aromatic rings was possible at temperatures as low as 160
      degrees C in the presence of oxygen. A mechanism for an oxygen-assisted
      aromatization of cylcoalkanes is proposed.

PMID- 19091085
TI  - How healthy are chronically ill patients after eight years of homeopathic
      treatment?--Results from a long term observational study.
AB  - BACKGROUND: Homeopathy is a highly debated but often used medical treatment. With
      this cohort study we aimed to evaluate health status changes under homeopathic
      treatment in routine care. Here we extend former results, now presenting data of
      an 8-year follow-up. METHODS: In a prospective, multicentre cohort study with 103
      homeopathic primary care practices in Germany and Switzerland, data from all
      patients (age >1 year) consulting the physician for the first time were observed.
      The main outcome measures were: The patients' perceived change in complaint
      severity (numeric rating scales from 0 = no complaint to 10 = maximal severity)
      and quality of life as measured by the SF-36 at baseline, and after 2 and 8
      years. RESULTS: A total of 3,709 patients were studied, 73% (2,722 adults, 72.8%
      female, age at baseline 41.0 +/- 12.3; 819 children, 48.4% female, age 6.5 +/-
      4.0) contributed data to the 8-year follow-up. The most frequent diagnoses were
      allergic rhinitis and headache in adults, and atopic dermatitis and multiple
      recurrent infections in children. Disease severity decreased significantly (p <
      0.001) between baseline, 2 and 8 years (adults from 6.2 +/- 1.7 to 2.9 +/- 2.2
      and 2.7 +/- 2.1; children from 6.1 +/- 1.8 to 2.1 +/- 2.0 and 1.7 +/- 1.9).
      Physical and mental quality of life sores also increased considerably. Younger
      age, female gender and more severe disease at baseline were factors predictive of
      better therapeutic success. CONCLUSION: Patients who seek homeopathic treatment
      are likely to improve considerably. These effects persist for as long as 8 years.

PMID- 19091087
TI  - Examining the significance of fingerprint-based classifiers.
AB  - BACKGROUND: Experimental examinations of biofluids to measure concentrations of
      proteins or their fragments or metabolites are being explored as a means of early
      disease detection, distinguishing diseases with similar symptoms, and drug
      treatment efficacy. Many studies have produced classifiers with a high
      sensitivity and specificity, and it has been argued that accurate results
      necessarily imply some underlying biology-based features in the classifier. The
      simplest test of this conjecture is to examine datasets designed to contain no
      information with classifiers used in many published studies. RESULTS: The
      classification accuracy of two fingerprint-based classifiers, a decision tree
      (DT) algorithm and a medoid classification algorithm (MCA), are examined. These
      methods are used to examine 30 artificial datasets that contain random
      concentration levels for 300 biomolecules. Each dataset contains between 30 and
      300 Cases and Controls, and since the 300 observed concentrations are randomly
      generated, these datasets are constructed to contain no biological information. A
      modest search of decision trees containing at most seven decision nodes finds a
      large number of unique decision trees with an average sensitivity and specificity
      above 85% for datasets containing 60 Cases and 60 Controls or less, and for
      datasets with 90 Cases and 90 Controls many DTs have an average sensitivity and
      specificity above 80%. For even the largest dataset (300 Cases and 300 Controls)
      the MCA procedure finds several unique classifiers that have an average
      sensitivity and specificity above 88% using only six or seven features.
      CONCLUSION: While it has been argued that accurate classification results must
      imply some biological basis for the separation of Cases from Controls, our
      results show that this is not necessarily true. The DT and MCA classifiers are
      sufficiently flexible and can produce good results from datasets that are
      specifically constructed to contain no information. This means that a chance
      fitting to the data is possible. All datasets used in this investigation are
      available on the web.

PMID- 19091088
TI  - Impact of early applied upper limb stimulation: the EXPLICIT-stroke programme
      design.
AB  - BACKGROUND: Main claims of the literature are that functional recovery of the
      paretic upper limb is mainly defined within the first month post stroke and that
      rehabilitation services should preferably be applied intensively and in a task
      oriented way within this particular time window. EXplaining PLastICITy after
      stroke (acronym EXPLICIT-stroke) aims to explore the underlying mechanisms of
      post stroke upper limb recovery. Two randomized single blinded trials form the
      core of the programme, investigating the effects of early modified Constraint
      Induced Movement Therapy (modified CIMT) and EMG-triggered Neuro-Muscular
      Stimulation (EMG-NMS) in patients with respectively a favourable or poor
      probability for recovery of dexterity. METHODS/DESIGN: 180 participants suffering
      from an acute, first-ever ischemic stroke will be recruited. Functional prognosis
      at the end of the first week post stroke is used to stratify patient into a poor
      prognosis group for upper limb recovery (N = 120, A2 project) and a group with a
      favourable prognosis (N = 60, A1 project). Both groups will be randomized to an
      experimental arm receiving respectively modified CIMT (favourable prognosis) or
      EMG-NMS (poor prognosis) for 3 weeks or to a control arm receiving usual care.
      Primary outcome variable will be the Action Research Arm Test (ARAT), assessed at
      1,2,3,4,5, 8, 12 and 26 weeks post stroke. To study the impact of modified CIMT
      or EMG-NMS on stroke recovery mechanisms i.e. neuroplasticity, compensatory
      movements and upper limb neuromechanics, 60 patients randomly selected from
      projects A1 and A2 will undergo TMS, kinematical and haptic robotic measurements
      within a repeated measurement design. Additionally, 30 patients from the A1
      project will undergo fMRI at baseline, 5 and 26 weeks post stroke. CONCLUSION:
      EXPLICIT stroke is a 5 year translational research programme which main aim is to
      investigate the effects of early applied intensive intervention for regaining
      dexterity and to explore the underlying mechanisms that are involved in regaining
      upper limb function after stroke. EXPLICIT-stroke will provide an answer to the
      key question whether therapy induced improvements are due to either a reduction
      of basic motor impairment by neural repair i.e. restitution of function and/or
      the use of behavioural compensation strategies i.e. substitution of function.

PMID- 19091089
TI  - The impact of adverse events in the intensive care unit on hospital mortality and
      length of stay.
AB  - BACKGROUND: Adverse events (AEs) are patient injuries caused by medical care.
      Previous studies have reported increased mortality rates and prolonged hospital
      length of stay in patients having an AE. However, these studies have not
      adequately accounted for potential biases which might influence these
      associations. We performed this study to measure the independent influence of
      intensive care unit (ICU) based AEs on in-hospital mortality and hospital length
      of stay. METHODS: Prospective cohort study in an academic tertiary-care ICU.
      Patients were monitored daily for adverse clinical occurrences. Data about
      adverse clinical occurrences were reviewed by a multidisciplinary team who rated
      whether they were AEs and whether they were preventable. We determined the
      association of AEs in the ICU with time to death and time to hospital discharge
      using multivariable survival analysis models. RESULTS: We evaluated 207
      critically ill patients (81% required mechanical ventilation, median Glasgow Coma
      Scale = 8, median predicted mortality = 31%). Observed mortality rate and
      hospital length of stay were 25% (95% CI 19%-31%) and 15 days (IQR 8-34 days),
      respectively. ICU-based AEs and preventable AEs occurred in 40 patients (19%, 95%
      CI 15%-25%) and 21 patients (10%, 95% CI 7%-15%), respectively. ICU-based AEs and
      preventable AEs were not significantly associated with time to in-hospital death
      (HR = 0.93, 95% CI 0.44-1.98 and HR = 0.72 95% CI 0.25-2.04, respectively). ICU
      based AEs and preventable AEs were independently associated with time to hospital
      discharge ((HR = 0.50, 95% CI 0.31-0.81 and HR = 0.46 95% CI 0.23-0.91,
      respectively)). ICU-based AEs were associated with an average increase in
      hospital length of stay of 31 days. CONCLUSION: The impact of AEs on hospital
      length of stay was clinically relevant. Larger studies are needed to conclusively
      measure the association between preventable AEs and patient outcomes.

PMID- 19091090
TI  - Genetic polymorphisms are associated with serum levels of sex hormone binding
      globulin in postmenopausal women.
AB  - BACKGROUND: Estrogen activity plays a critical role in bone homeostasis. The
      serum levels of sex hormone binding globulin (SHBG) influence free estrogen
      levels and activity on target tissues. The objective of this study was to analyze
      the influence of common polymorphisms of the SHBG gene on serum SHBG, bone
      mineral density (BMD), and osteoporotic fractures. METHODS: Four biallelic
      polymorphisms of the SHBG gene were studied by means of Taqman assays in 753
      postmenopausal women. BMD was measured by DXA and serum SHBG was measured by
      ELISA. RESULTS: Age, body weight, and two polymorphisms of the SHBG gene (rs6257
      and rs1799941 [A/G]) were significantly associated with serum SHBG in unadjusted
      and age- and weight-adjusted models. Alleles at the rs1799941 locus showed the
      strongest association with serum SHBG (p=0.0004). The difference in SHBG levels
      between women with AA and GG genotypes at the rs1799941 locus was 39%. There were
      no significant differences in BMD across SHBG genotypes. The genotypes showed
      similar frequency distributions in control women and women with vertebral or hip
      fractures. CONCLUSION: Some common genetic variants of the SHBG gene, and
      particularly an A/G polymorphism situated in the 5' region, influence serum SHBG
      levels. However, a significant association with BMD or osteoporotic fractures has
      not been demonstrated.

PMID- 19091091
TI  - Decision making preferences in the medical encounter--a factorial survey design.
AB  - BACKGROUND: Up to now it has not been systematically investigated in which kind
      of clinical situations a consultation style based on shared decision making (SDM)
      is preferred by patients and physicians. We suggest the factorial survey design
      to address this problem.This method, which so far has hardly been used in health
      service research, allows to vary relevant factors describing clinical situations
      as variables systematically in an experimental random design and to investigate
      their importance in large samples. METHODS/DESIGN: To identify situational
      factors for the survey we first performed a literature search which was followed
      by a qualitative interview study with patients, physicians and health care
      experts. As a result, 7 factors (e.g. "Reason for consultation" and "Number of
      therapeutic options") with 2 to 3 levels (e.g. "One therapeutic option" and "More
      than one therapeutic option") will be included in the study. For the survey the
      factor levels will be randomly combined to short stories describing different
      treatment situations.A randomized sample of all possible short stories will be
      given to at least 300 subjects (100 GPs, 100 patients and 100 members of self
      help groups) who will be asked to rate how the decision should be made. Main
      outcome measure is the preference for participation in the decision making
      process in the given clinical situation.Data analysis will estimate the effects
      of the factors on the rating and also examine differences between groups.
      DISCUSSION: The results will reveal the effects of situational variations on
      participation preferences. Thus, our findings will contribute to the
      understanding of normative values in the medical decision making process and will
      improve future implementation of SDM and decision aids.

PMID- 19091092
TI  - Decreased postnatal neurogenesis in the hippocampus combined with stress
      experience during adolescence is accompanied by an enhanced incidence of
      behavioral pathologies in adult mice.
AB  - BACKGROUND: Adolescence is a vulnerable period in that stress experienced during
      this time can affect the incidence of psychiatric disorders later, during
      adulthood. Neurogenesis is known to be involved in the postnatal development of
      the brain, but its role in determining an individual's biological vulnerability
      to the onset of psychiatric disorders has not been addressed. RESULTS: We
      examined the role of postnatal neurogenesis during adolescence, a period between
      3 to 8 weeks of age in rodents. Mice were X-irradiated at 4 weeks of age, to
      inhibit postnatal neurogenesis in the sub-granule cell layer of the hippocampus.
      Electrical footshock stress (FSS) was administered at 8 weeks old, the time at
      which neurons being recruited to granule cell layer were those that had begun
      their differentiation at 4 weeks of age, during X-irradiation. X-irradiated mice
      subjected to FSS during adolescence exhibited decreased locomotor activity in the
      novel open field, and showed prepulse inhibition deficits in adulthood. X
      irradiation or FSS alone exerted no effects on these behaviors. CONCLUSION: These
      results suggest that mice with decreased postnatal neurogenesis during
      adolescence exhibit vulnerability to stress, and that persistence of this
      condition may result in decreased activity, and cognitive deficits in adulthood.

PMID- 19091093
TI  - Willingness to pay to sustain and expand National Health Insurance services in
      Taiwan.
AB  - BACKGROUND: The purpose of the present study was to investigate people's
      willingness to pay to sustain the current National Health Insurance (NHI) program
      in Taiwan and to extend that program to cover long-term care services. METHODS: A
      survey was administered to 1800 inpatients and 1800 outpatients, selected from
      health care facilities across all accreditation levels that were operating under
      the supervision of six different regional branches of Taiwan's Bureau of National
      Health Insurance (BNHI). We used a contingent valuation method with closed-ended
      questions to elicit participants' willingness to pay for continued national heath
      insurance and additional institutional long-term care services. We divided
      participants into six subgroups and asked individuals in these groups referendum
      like yes-no questions about whether they were willing to pay one of six price
      bids: New Taiwan Dollar (NT$) 50, NT$100, NT$200, NT$300, NT$400, or NT$500.
      Logistic regression was used to analyze willingness to pay. RESULTS: We found
      maximum willingness to pay for continued coverage by the NHI program and
      additional institutional long-term care services to be NT$66 and NT$137 dollars
      per month, respectively. CONCLUSION: We found that people were willing to pay
      more for their insurance coverage. With regard to methodology, we also found that
      using a contingent valuation method to elicit peoples' willingness to pay for
      health policy issues is valid. The results of the present referendum-like study
      can serve as a reference for future policy decision making.

PMID- 19091094
TI  - Ileoileal intussusception induced by a gastrointestinal stromal tumor.
AB  - BACKGROUND: Gastrointestinal stromal tumors are mesenchymal tumors of the
      gastrointestinal tract of varying malignant potential that are believed to
      originate from neoplastic transformation of the interstitial cells of Cajal. They
      may occur anywhere along the gastrointestinal tract, but most commonly arise in
      the stomach or small intestine. They usually grow exophytically invading adjacent
      organs or perforating into the peritoneal cavity. They may also cause bleeding or
      obstructive symptoms. Intussusception and obstruction is a very uncommon
      presentation of these lesions because of their tendency to grow in an exraluminal
      fashion. CASE PRESENTATION: We present an unusual case of ileoileal
      intussusception in a 79-year-old female patient caused by a gastrointestinal
      stromal tumor located in the terminal ileum, and review the diagnostic and
      therapeutic approach highlighting the difficulty in diagnosing this entity
      preoperatively as a cause for intestinal obstruction. CONCLUSION: This case
      presents an unusual malignant cause of adult intussusception and highlights the
      importance of computed tomography scanning in the accurate diagnosis of this rare
      entity.

PMID- 19091095
TI  - Axillary nerve conduction changes in hemiplegia.
AB  - AIM: To prove the possibility of axillary nerve conduction changes following
      shoulder subluxation due to hemiplegia, in order to investigate the usefulness of
      screening nerve conduction studies in patients with hemiplegia for finding
      peripheral neuropathy. METHODS: Forty-four shoulders of twenty-two patients with
      a first-time stroke having flaccid hemiplegia were tested, 43 +/- 12 days after
      stroke onset. Wasting and weakness of the deltoid were present in the involved
      side. Motor nerve conduction latency and compound muscle action potential (CMAP)
      amplitude were measured along the axillary nerve, comparing the paralyzed to the
      sound shoulder. The stimulation was done at the Erb's point whilst the recording
      needle electrode was inserted into the deltoid muscle 4 cm directly beneath the
      lateral border of the acromion. Wilcoxon signed rank test was used to compare the
      motor conduction between the sound and the paralytic shoulder. Mann-Whitney test
      was used to compare between plegic and sound shoulder in each side. RESULTS: Mean
      motor nerve conduction latency time to the deltoid muscle was 8.49, SD 4.36 ms in
      the paralyzed shoulder and 5.17, SD 1.35 ms in the sound shoulder (p < 0.001).
      Mean compound muscle action potential (CMAP) amplitude was 2.83, SD 2.50 mV in
      the paralyzed shoulder and was 7.44, SD 5.47 mV in the sound shoulder (p <
      0.001). Patients with right paralyzed shoulder compared to patients with right
      sound shoulder (p < 0.001, 1-sided for latency; p = 0.003, 1-sided for
      amplitude), and patients with left paralyzed shoulder compared to patients with
      left sound shoulder (p = 0.011, 1-sided for latency, p = 0.001, 1-sided for
      amplitude), support the same outcomes. The electro-physiological changes in the
      axillary nerve may appear during the first six weeks after stroke breakout.
      CONCLUSION: Continuous traction of the axillary nerve, as in hypotonic shoulder,
      may affect the electro-physiological properties of the nerve. It most probably
      results from subluxation of the head of the humerus, causing demyelinization and
      even axonopathy. Slowing of the conduction velocities of the axillary nerve in
      the paralyzed shoulders may be related also to the lowering of the skin
      temperature and muscular atrophy in the same limb. The usefulness of routine
      screening nerve conduction studies in the shoulder of hemiplegic patients seems
      to be advocated.

PMID- 19091096
TI  - Functional identification of HugZ, a heme oxygenase from Helicobacter pylori.
AB  - BACKGROUND: Iron is recognized as an important trace element, essential for most
      organisms including pathogenic bacteria. HugZ, a protein related to heme iron
      utilization, is involved in bacterial acquisition of iron from the host. We
      previously observed that a hugZ homologue is correlated with the adaptive
      colonization of Helicobacter pylori (H. pylori), a major gastro-enteric pathogen.
      However, its exact physiological role remains unclear. RESULTS: A gene homologous
      to hugZ, designated hp0318, identified in H. pylori ATCC 26695, exhibits 66%
      similarity to cj1613c of Campylobacter jejuni NCTC 11168. Soluble 6 x His fused
      HugZ protein was expressed in vitro. Hemin-agrose affinity analysis indicated
      that the recombinant HugZ protein can bind to hemin. Absorption spectroscopy at
      411 nm further revealed a heme:HugZ binding ratio of 1:1. Enzymatic assays showed
      that purified recombinant HugZ protein can degrade hemin into biliverdin and
      carbon monoxide in the presence of either ascorbic acid or NADPH and cytochrome
      P450 reductase. The biochemical and enzymatic characteristics agreed closely with
      those of Campylobacter jejuni Cj1613c protein, implying that hp0318 is a
      functional member of the HugZ family. A hugZ deletion mutant was obtained by
      homologous recombination. This mutant strain showed poor growth when hemoglobin
      was provided as the source of iron, partly because of its failure to utilize
      hemoglobin efficiently. Real-time quantitative PCR also confirmed that the
      expression of hugZ was regulated by iron levels. CONCLUSION: These findings
      provide biochemical and genetic evidence that hugZ (hp0318) encodes a heme
      oxygenase involved in iron release/uptake in H. pylori.

PMID- 19091098
TI  - Anaplastic carcinoma of the pancreas producing granulocyte-colony stimulating
      factor: a case report.
AB  - INTRODUCTION: The granulocyte-colony stimulating factor-producing tumor was first
      reported in 1977, however, anaplastic pleomorphic type carcinoma of the pancreas
      producing granulocyte-colony stimulating factor is still rare. CASE PRESENTATION:
      A 63-year-old man was admitted to our hospital with body weight loss (-10 kg
      during months) and upper abdominal pain from 3 weeks. Abdominal computed
      tomography demonstrated a pancreatic tumor 10 cm in size and multiple low-density
      areas in the liver. On admission, the peripheral leukocyte count was elevated to
      91,500/mm3 and the serum concentration of granulocyte-colony stimulating factor
      was 134 pg/mL (normal, < 18.1 pg/mL). Based on liver biopsy findings, the tumor
      was classified as an anaplastic pleomorphic-type carcinoma. Immunohistochemical
      staining showed that pancreatic carcinoma cells were positive for granulocyte
      colony stimulating factor. The patient developed interstitial pneumonia, probably
      caused by granulocyte-colony stimulating factor, and died 11 days after
      admission. CONCLUSION: This is a rare case report of anaplastic pleomorphic-type
      carcinoma of the pancreas producing granulocyte-colony stimulating factor and
      confirmed by immunohistochemistry.

PMID- 19091097
TI  - Outcome in recurrent head neck cancer treated with salvage-IMRT.
AB  - BACKGROUND: Recurrent head neck cancer (rHNC) is a known unfavourable prognostic
      condition.The purpose of this work was to analyse our rHNC subgroup treated with
      salvage-intensity modulated radiation therapy (IMRT) for curable recurrence after
      initial surgery alone. PATIENTS: Between 4/2003-9/2008, 44 patients with squamous
      cell rHNC were referred for IMRT, mean/median 33/21 (3-144) months after initial
      surgery. None had prior head neck radiation. 41% underwent definitive, 59%
      postoperative IMRT (66-72.6 Gy). 70% had simultaneous chemotherapy. METHODS:
      Retrospective analysis of the outcome following salvage IMRT in rHNC patients was
      performed. RESULTS: After mean/median 25/21 months (3-67), 22/44 (50%) patients
      were alive with no disease; 4 (9%) were alive with disease. 18 patients (41%)
      died of disease. Kaplan Meier 2-year disease specific survival (DSS), disease
      free survival (DFS), local and nodal control rates of the cohort were 59/49/56
      and 68%, respectively.Known risk factors (advanced initial pTN, marginal initial
      resection, multiple recurrences) showed no significant outcome differences. Risk
      factors and the presence of macroscopic recurrence gross tumor volume (rGTV) in
      oral cavity patients vs others resulted in statistically significantly lower DSS
      (30 vs 70% at 2 years, p = 0.03). With respect to the assessed unfavourable
      outcome following salvage treatment, numbers needed to treat to avoid one
      recurrence with initial postoperative IMRT have, in addition, been calculated.
      CONCLUSION: A low salvage rate of only approximately 50% at 2 years was found.
      Calculated numbers of patients needed to treat with postoperative radiation after
      initial surgery, in order to avoid recurrence and tumor-specific death, suggest a
      rather generous use of adjuvant irradiation, usually with simultaneous
      chemotherapy.

PMID- 19091099
TI  - The use of health-related quality of life (HRQOL) in children and adolescents as
      an outcome criterion to evaluate family oriented support for young carers in
      Germany: an integrative review of the literature.
AB  - BACKGROUND: Young people below the age of 18, whose lives are affected by looking
      after a relative with a disability or long-term illness, are called young carers.
      Evidence based family oriented support for young carers and their families in
      Germany is currently being developed. To allow for scientific evaluation, an
      outcome criterion needs to be chosen. Until today, there are no assessment
      instruments available, which focus on young carer's specific demands and needs.
      As HRQOL seems to be an adequate alternative outcome criterion, an integrative
      review of the literature was carried out to verify this assumption. METHODS: The
      aim of the integrative review was to get information about a) the concept and the
      common definition of HRQOL in children, b) preferable HRQOL assessment techniques
      in children, and c) the relevance of HRQOL measures for the population of young
      carers. An additional aim of the review was to give advice on which instrument
      fits best to assess young carer's HRQOL in Germany. Searches were conducted in
      PubMed in order to obtain papers reporting about a) the development or
      psychometric assessment of instruments measuring HRQOL in children and
      adolescents up to the age of 18, and b) on the conceptual framework of HRQOL in
      children. RESULTS: HRQOL is a multidimensional construct covering physical,
      emotional, mental, social, and behavioural components of well-being and
      functioning as subjective perceived by a person depending on the cultural context
      and value system one is living in. Young carer's problems and needs are well
      covered by these common domains of HRQOL. Since no specific HRQOL-measures are
      available to address young carers, a generic one has to be chosen which a) has
      been created for use in children, b) allows self- and proxy-report, and c) has
      good psychometric testing results. Comparing four generic measures with currently
      best published psychometric testing results, items of the KIDSCREEN cover young
      carer's specific problems most accurate. CONCLUSION: The KIDSCREEN questionnaires
      seems adequate to evaluate the intervention as their items cover young carer's
      needs and problems most accurate.

PMID- 19091100
TI  - Ethical issues in implementation research: a discussion of the problems in
      achieving informed consent.
AB  - BACKGROUND: Improved quality of care is a policy objective of health care systems
      around the world. Implementation research is the scientific study of methods to
      promote the systematic uptake of clinical research findings into routine clinical
      practice, and hence to reduce inappropriate care. It includes the study of
      influences on healthcare professionals' behaviour and methods to enable them to
      use research findings more effectively. Cluster randomized trials represent the
      optimal design for evaluating the effectiveness of implementation strategies.
      Various codes of medical ethics, such as the Nuremberg Code and the Declaration
      of Helsinki inform medical research, but their relevance to cluster randomised
      trials in implementation research is unclear. This paper discusses the
      applicability of various ethical codes to obtaining consent in cluster trials in
      implementation research. DISCUSSION: The appropriate application of biomedical
      codes to implementation research is not obvious. Discussion of the nature and
      practice of informed consent in implementation research cluster trials must
      consider the levels at which consent can be sought, and for what purpose it can
      be sought. The level at which an intervention is delivered can render the idea of
      patient level consent meaningless. Careful consideration of the ownership of
      information, and rights of access to and exploitation of data is required. For
      health care professionals and organizations, there is a balance between clinical
      freedom and responsibility to participate in research. SUMMARY: While ethical
      justification for clinical trials relies heavily on individual consent, for
      implementation research aspects of distributive justice, economics, and political
      philosophy underlie the debate. Societies may need to trade off decisions on the
      choice between individualized consent and valid implementation research. We
      suggest that social sciences codes could usefully inform the consideration of
      implementation research by members of Research Ethics Committees.

PMID- 19091102
TI  - Eventration of diaphragm with gastric volvulus: a case report.
AB  - BACKGROUND: Eventration of diaphragm associated with gastric volvulus is an
      uncommon condition. CASE PRESENTATION: We are reporting a case of a 60-year-old
      male having left sided total diaphragmatic eventration associated with chronic
      intermittent organo-axial gastric volvulus. The patient presented with
      progressive dyspnea and intermittent gastrointestinal symptoms. Plication of left
      hemidiaphragm with anterior gastropexy was performed through an abdominal
      approach. Postoperatively the patient's symptoms improved. CONCLUSION:
      Symptomatic gastric volvulus associated with diaphragmatic eventration is a
      surgical emergency and always requires surgical repair.

PMID- 19091103
TI  - An unusual and difficult diagnosis of intestinal obstruction: The abdominal
      cocoon. Case report and review of the literature.
AB  - Since publication of our article, "An unusual and difficult diagnosis of
      intestinal obstruction: The abdominal cocoon. Case report and review of the
      literature." World J Emerg Surg. 2006, 1: 8 we believe that the case mentioned
      should have been described as a 'peritoneal encapsulation' rather than 'abdominal
      cocoon' as concluded in the original publication.

PMID- 19091101
TI  - Lack of association between glucocorticoid use and presence of the metabolic
      syndrome in patients with rheumatoid arthritis: a cross-sectional study.
AB  - INTRODUCTION: Rheumatoid arthritis (RA) associates with excessive cardiovascular
      morbidity and mortality, attributed to both traditional and novel cardiovascular
      risk factors. The metabolic syndrome, a cluster of classical cardiovascular risk
      factors, including hypertension, obesity, glucose intolerance, and dyslipidaemia,
      is highly prevalent in RA. Reports suggest that long-term glucocorticoid (GC) use
      may exacerbate individual cardiovascular risk factors, but there have been no
      studies in RA to assess whether it associates with the metabolic syndrome. We
      examined whether GC exposure associates with the presence of metabolic syndrome
      in patients with RA. METHODS: RA patients (n = 398) with detailed clinical and
      laboratory assessments were categorised into three groups according to GC
      exposure: no/limited (<3 months) exposure (NE), low-dose (<7.5 mg/day) long-term
      exposure (LE), and medium-dose (greater than or equal to 7.5 mg to 30 mg/day)
      long-term exposure (ME). The metabolic syndrome was defined using the National
      Cholesterol Education Programme III guidelines. The association of GC exposure
      with the metabolic syndrome was evaluated using binary logistic regression.
      RESULTS: The metabolic syndrome was present in 40.1% of this population and its
      prevalence did not differ significantly between the GC exposure groups (NE 37.9%
      versus LE 40.7% versus ME 50%, P = 0.241). Binary logistic regression did not
      demonstrate any increased odds for the metabolic syndrome when comparing ME with
      LE (odds ratio = 1.64, 95% confidence interval 0.92 to 2.92, P = 0.094) and
      remained non significant after adjusting for multiple potential confounders.
      CONCLUSIONS: Long-term GC exposure does not appear to associate with a higher
      prevalence of the metabolic syndrome in patients with RA. The components of the
      metabolic syndrome may already be extensively modified by other processes in RA
      (including chronic inflammation and treatments other than GCs), leaving little
      scope for additive effects of GCs.

PMID- 19091104
TI  - Struggles, strengths, and strategies: an ethnographic study exploring the
      experiences of adolescents living with an ostomy.
AB  - BACKGROUND: Adolescents with IBD requiring ostomy surgery experience
      perioperative needs that may exceed those of patients experiencing other major
      abdominal surgery 1. This procedure requires ongoing and vigilant daily care and
      management. Gastrointestinal symptoms and complications impose psychological and
      social stresses on young patients 2, and the procedure results in body image
      changes and daily regimens of self-care. This study aimed to explore adolescents'
      experiences and quality of life following ostomy surgery. METHODS: Ethnographic
      interviews and a subsequent focus group were conducted with 20 adolescents with
      an ostomy or j-pouch being treated at the Hospital for Sick Children in Toronto,
      Canada. Interviews were transcribed verbatim and subjected to theme generation.
      RESULTS: Findings suggest that adolescents are profoundly affected by their
      ostomy. Adolescents convey strength as well as adjustment struggles. Identified
      impacts include body intrusion and body image changes, decreased independence,
      secrecy about the ostomy, adjustment over time, challenges for the family, and
      strategies for constructively moving forward. CONCLUSION: Implications address
      the importance of ensuring meaningful opportunities to understand and reframe the
      stresses of illness. An ongoing clinical challenge involves the promotion of a
      healthy self-esteem and psychosocial adjustment for these adolescents and their
      families. Finding effective ways to minimize stress and embarrassment and reframe
      personal shame, constitute important clinical priorities. Opportunities for peer
      support and family dialogue may assist in clarifying worries and easing the
      burden carried by these young persons. Flexible and adequately funded resources
      are advocated in fostering quality of life.

PMID- 19091106
TI  - Survey of microsatellite clustering in eight fully sequenced species sheds light
      on the origin of compound microsatellites.
AB  - BACKGROUND: Compound microsatellites are a special variation of microsatellites
      in which two or more individual microsatellites are found directly adjacent to
      each other. Until now, such composite microsatellites have not been investigated
      in a comprehensive manner. RESULTS: Our in silico survey of microsatellite
      clustering in genomes of Homo sapiens, Maccaca mulatta, Mus musculus, Rattus
      norvegicus, Ornithorhynchus anatinus, Gallus gallus, Danio rerio and Drosophila
      melanogaster revealed an unexpected high abundance of compound microsatellites.
      About 4 - 25% of all microsatellites could be categorized as compound
      microsatellites. Compound microsatellites are approximately 15 times more
      frequent than expected under the assumption of a random distribution of
      microsatellites. Interestingly, microsatellites do not only tend to cluster but
      the adjacent repeat types of compound microsatellites have very similar motifs:
      in most cases (>90%) these motifs differ only by a single mutation (base
      substitution or indel). We propose that the majority of the compound
      microsatellites originates by duplication of imperfections in a microsatellite
      tract. This process occurs mostly at the end of a microsatellite, leading to a
      new repeat type and a potential microsatellite repeat track. CONCLUSION: Our
      findings suggest a more dynamic picture of microsatellite evolution than
      previously believed. Imperfections within microsatellites might not only cause
      the "death" of microsatellites they might also result in their "birth".

PMID- 19091105
TI  - Shortage in general practice despite the feminisation of the medical workforce: a
      seeming paradox? A cohort study.
AB  - BACKGROUND: Female medical students often prefer primary care specialties, while
      male students appear to be attracted to hospital specialties. Notwithstanding the
      steady feminisation of medicine, in many countries there are still difficulties
      in recruiting trainees for general practice. This seeming paradox raises the
      question on what specific role gender plays in a specialty choice. The authors
      looked at the (a) the role of gender in general practice specialty choice of
      Dutch medical students, (b) the decisive factors in career choice and relation of
      gender to these, and (c) differences in how male and female students are
      influenced by the GP clerkship. METHODS: A cohort of 206 final year medical
      students at the Maastricht University, the Netherlands were asked to complete a
      questionnaire focusing on career preferences before and after a 12-week general
      practice clerkship and at graduation, a couple of months later. RESULTS: Gender
      was significantly related to willingness to become a GP in bivariate analysis.
      Adding variables in multivariate analysis made this effect disappear. While
      females expressed overall higher preference for general practice than males,
      after the GP clerkship likelihood of choosing general practice increased with 38%
      among male and 22% among female students. After graduation, interest in general
      practice had dropped, mainly among females. Attitudes predicting a GP career
      choice were: extrinsic career motivation before the clerkship, and the content of
      GP work (patient contacts, treatments) and motivation to work with chronic and
      palliative patients after the clerkship. CONCLUSION: Gender 'as such' appeared
      not to be a distinctive predictor of specialty choice. It is students' attitudes
      towards GP work and preferred patient category that determine the career choice
      in general practice. However, more male students were positively influenced by
      the GP clerkship than female students. The motivating effect of the clerkship is
      not long lasting. Especially female graduates change their interest in favour of
      other specialties, which may explain why eventually few students choose general
      practice. It might be worthwhile to reinforce an initial preference for general
      practice by motivational guidance throughout the whole period of clerkships.

PMID- 19091107
TI  - Evidence-informed health policy 1 - synthesis of findings from a multi-method
      study of organizations that support the use of research evidence.
AB  - BACKGROUND: Organizations have been established in many countries and
      internationally to support the use of research evidence by producing clinical
      practice guidelines, undertaking health technology assessments, and/or directly
      supporting the use of research evidence in developing health policy on an
      international, national, and state or provincial level. Learning from these
      organizations can reduce the need to 'reinvent the wheel' and inform decisions
      about how best to organize support for such organizations, particularly in low-
      and middle-income countries (LMICs). METHODS: We undertook a multi-method study
      in three phases - a survey, interviews, and case descriptions that drew on site
      visits - and in each of the second and third phases we focused on a purposive
      sample of those involved in the previous phase. We used the seven main
      recommendations that emerged from the advice offered in the interviews to
      organize much of the synthesis of findings across phases and methods. We used a
      constant comparative method to identify themes from across phases and methods.
      RESULTS: Seven recommendations emerged for those involved in establishing or
      leading organizations that support the use of research evidence in developing
      health policy: 1) collaborate with other organizations; 2) establish strong links
      with policymakers and involve stakeholders in the work; 3) be independent and
      manage conflicts of interest among those involved in the work; 4) build capacity
      among those working in the organization; 5) use good methods and be transparent
      in the work; 6) start small, have a clear audience and scope, and address
      important questions; and 7) be attentive to implementation considerations, even
      if implementation is not a remit. Four recommendations emerged for the World
      Health Organization (WHO) and other international organizations and networks: 1)
      support collaborations among organizations; 2) support local adaptation efforts;
      3) mobilize support; and 4) create global public goods. CONCLUSION: This
      synthesis of findings from a multi-method study, along with the more detailed
      findings from each of the three phases of the study (which are reported in the
      three following articles in the series), provide a strong basis on which
      researchers, policymakers, international organizations (and networks) like WHO
      can respond to the growing chorus of voices calling for efforts to support the
      use of research evidence in developing health policy.

PMID- 19091108
TI  - Evidence-informed health policy 2 - survey of organizations that support the use
      of research evidence.
AB  - BACKGROUND: Previous surveys of organizations that support the development of
      evidence-informed health policies have focused on organizations that produce
      clinical practice guidelines (CPGs) or undertake health technology assessments
      (HTAs). Only rarely have surveys focused at least in part on units that directly
      support the use of research evidence in developing health policy on an
      international, national, and state or provincial level (i.e., government support
      units, or GSUs) that are in some way successful or innovative or that support the
      use of research evidence in low- and middle-income countries (LMICs). METHODS: We
      drew on many people and organizations around the world, including our project
      reference group, to generate a list of organizations to survey. We modified a
      questionnaire that had been developed originally by the Appraisal of Guidelines,
      Research and Evaluation in Europe (AGREE) collaboration and adapted one version
      of the questionnaire for organizations producing CPGs and HTAs, and another for
      GSUs. We sent the questionnaire by email to 176 organizations and followed up
      periodically with non-responders by email and telephone. RESULTS: We received
      completed questionnaires from 152 (86%) organizations. More than one-half of the
      organizations (and particularly HTA agencies) reported that examples from other
      countries were helpful in establishing their organization. A higher proportion of
      GSUs than CPG- or HTA-producing organizations involved target users in the
      selection of topics or the services undertaken. Most organizations have few (five
      or fewer) full-time equivalent (FTE) staff. More than four-fifths of
      organizations reported providing panels with or using systematic reviews. GSUs
      tended to use a wide variety of explicit valuation processes for the research
      evidence, but none with the frequency that organizations producing CPGs, HTAs, or
      both prioritized evidence by its quality. Between one-half and two-thirds of
      organizations do not collect data systematically about uptake, and roughly the
      same proportions do not systematically evaluate their usefulness or impact in
      other ways. CONCLUSION: The findings from our survey, the most broadly based of
      its kind, both extend or clarify the applicability of the messages arising from
      previous surveys and related documentary analyses, such as how the 'principles of
      evidence-based medicine dominate current guideline programs' and the importance
      of collaborating with other organizations. The survey also provides a description
      of the history, structure, processes, outputs, and perceived strengths and
      weaknesses of existing organizations from which those establishing or leading
      similar organizations can draw.

PMID- 19091109
TI  - Evidence-informed health policy 3 - interviews with the directors of
      organizations that support the use of research evidence.
AB  - BACKGROUND: Only a small number of previous efforts to describe the experiences
      of organizations that produce clinical practice guidelines (CPGs), undertake
      health technology assessments (HTAs), or directly support the use of research
      evidence in developing health policy (i.e., government support units, or GSUs)
      have relied on interviews and then only with HTA agencies. Interviews offer the
      potential for capturing experiences in great depth, particularly the experiences
      of organizations that may be under-represented in surveys. METHODS: We
      purposively sampled organizations from among those who completed a questionnaire
      in the first phase of our three-phase study, developed and piloted a semi
      structured interview guide, and conducted the interviews by telephone, audio
      taped them, and took notes simultaneously. Binary or categorical responses to
      more structured questions were counted when possible. Themes were identified from
      among responses to semi-structured questions using a constant comparative method
      of analysis. Illustrative quotations were identified to supplement the narrative
      description of the themes. RESULTS: We interviewed the director (or his or her
      nominee) in 25 organizations, of which 12 were GSUs. Using rigorous methods that
      are systematic and transparent (sometimes shortened to 'being evidence-based')
      was the most commonly cited strength among all organizations. GSUs more
      consistently described their close links with policymakers as a strength, whereas
      organizations producing CPGs, HTAs, or both had conflicting viewpoints about such
      close links. With few exceptions, all types of organizations tended to focus
      largely on weaknesses in implementation, rather than strengths. The advice
      offered to those trying to establish similar organizations include: 1)
      collaborate with other organizations; 2) establish strong links with policymakers
      and stakeholders; 3) be independent and manage conflicts of interest; 4) build
      capacity; 5) use good methods and be transparent; 6) start small and address
      important questions; and 7) be attentive to implementation considerations. The
      advice offered to the World Health Organization (WHO) and other international
      organizations and networks was to foster collaborations across organizations.
      CONCLUSION: The findings from our interview study, the most broadly based of its
      kind, extend to both CPG-producing organizations and GSUs the applicability of
      the messages arising from previous interview studies of HTA agencies, such as to
      collaborate with other organizations and to be attentive to implementation
      considerations. Our interview study also provides a rich description of
      organizations supporting the use of research evidence, which can be drawn upon by
      those establishing or leading similar organizations in LMICs.

PMID- 19091110
TI  - Evidence-informed health policy 4 - case descriptions of organizations that
      support the use of research evidence.
AB  - BACKGROUND: Previous efforts to produce case descriptions have typically not
      focused on the organizations that produce research evidence and support its use.
      External evaluations of such organizations have typically not been analyzed as a
      group to identify the lessons that have emerged across multiple evaluations. Case
      descriptions offer the potential for capturing the views and experiences of many
      individuals who are familiar with an organization, including staff, advocates,
      and critics. METHODS: We purposively sampled a subgroup of organizations from
      among those that participated in the second (interview) phase of the study and
      (once) from among other organizations with which we were familiar. We developed
      and pilot-tested a case description data collection protocol, and conducted site
      visits that included both interviews and documentary analyses. Themes were
      identified from among responses to semi-structured questions using a constant
      comparative method of analysis. We produced both a brief (one to two pages)
      written description and a video documentary for each case. RESULTS: We conducted
      51 interviews as part of the eight site visits. Two organizational strengths were
      repeatedly cited by individuals participating in the site visits: use of an
      evidence-based approach (which was identified as being very time-consuming) and
      existence of a strong relationship between researchers and policymakers (which
      can be challenged by conflicts of interest). Two organizational weaknesses - a
      lack of resources and the presence of conflicts of interest - were repeatedly
      cited by individuals participating in the site visits. Participants offered two
      main suggestions for the World Health Organization (and other international
      organizations and networks): 1) mobilize one or more of government support,
      financial resources, and the participation of both policymakers and researchers;
      and 2) create knowledge-related global public goods. CONCLUSION: The findings
      from our case descriptions, the first of their kind, intersect in interesting
      ways with the messages arising from two systematic reviews of the factors that
      increase the prospects for research use in policymaking. Strong relationships
      between researchers and policymakers bodes well given such interactions appear to
      increase the prospects for research use. The time-consuming nature of an evidence
      based approach, on the other hand, suggests the need for more efficient
      production processes that are 'quick and clean enough.' Our case descriptions and
      accompanying video documentaries provide a rich description of organizations
      supporting the use of research evidence, which can be drawn upon by those
      establishing or leading similar organizations, particularly in low- and middle
      income countries.

PMID- 19091111
TI  - Single-epitope recognition imaging of native chromatin.
AB  - BACKGROUND: Direct visualization of chromatin has the potential to provide
      important insights into epigenetic processes. In particular, atomic force
      microscopy (AFM) can visualize single nucleosomes under physiological ionic
      conditions. However, AFM has mostly been applied to chromatin that has been
      reconstituted in vitro, and its potential as a tool for the dissection of native
      nucleosomes has not been explored. Recently we applied AFM to native Drosophila
      chromatin containing the centromere-specific histone 3 (CenH3), showing that it
      is greatly enriched in smaller particles. Taken together with biochemical
      analyses of CenH3 nucleosomes, we propose that centromeric nucleosomes are
      hemisomes, with one turn of DNA wrapped around a particle consisting of one
      molecule each of centromere-specific CenH3, H4, H2A and H2B. RESULTS: Here we
      apply a recognition mode of AFM imaging to directly identify CenH3 within histone
      core particles released from native centromeric chromatin. More than 90% of these
      particles were found to be tetrameric in height. The specificity of recognition
      was confirmed by blocking with a CenH3 peptide, and the strength of the
      interaction was quantified by force measurements. These results imply that the
      particles imaged by AFM are indeed mature CenH3-containing hemisomes. CONCLUSION:
      Efficient and highly specific recognition of CenH3 in histone core particles
      isolated from native centromeric chromatin demonstrates that tetramers are the
      predominant form of centromeric nucleosomes in mature tetramers. Our findings
      provide proof of principle that this approach can yield insights into chromatin
      biology using direct and rapid detection of native nucleosomes in physiological
      salt concentrations.

PMID- 19091112
TI  - Clarification of anomalies in the application of a 2La molecular karyotyping
      method for the malaria vector Anopheles gambiae.
AB  - BACKGROUND: Chromosomal inversions have been considered to be potentially
      important barriers to gene flow in many groups of animals through their effect on
      recombination suppression in heterokaryotypic individuals. Inversions can also
      enhance local adaptation in different groups of organisms and may often represent
      species-specific differences among closely related taxa. We conducted a study to
      characterize the 2La inversion karyotypes of An. gambiae sensu stricto mosquitoes
      sampled from the Kilombero Valley (Tanzania) using a newly designed PCR assay.
      RESULTS: We frequently encountered a (687 bp) fragment which was only present in
      the Kilombero Valley populations. Laboratory crossing between An. gambiae s.s.
      from Njage (Tanzania) and Kisumu (Western Kenya) populations resulted in F1
      offspring carrying the observed fragment. Karyotype analysis did not indicate
      differences in 2La region chromosome morphology between individuals carrying the
      PCR fragments, the 207 bp fragment, or the 687 bp fragement. CONCLUSION: The
      observed insertion/deletion polymorphism within the region amplified by the 2La
      PCR diagnostic test may confound the interpretation of this assay and should be
      well considered in order to maintain an acceptable level of reliability in
      studies using this assay to describe the distribution and frequency of the 2La
      inversion among natural populations of An. gambiae s.s.

PMID- 19091113
TI  - Psychiatrists' attitudes towards autonomy, best interests and compulsory
      treatment in anorexia nervosa: a questionnaire survey.
AB  - BACKGROUND: The compulsory treatment of anorexia nervosa is a contentious issue.
      Research suggests that psychiatrists have a range of attitudes towards patients
      suffering from anorexia nervosa, and towards the use of compulsory treatment for
      the disorder. METHODS: A postal self-completed attitudinal questionnaire was sent
      to senior psychiatrists in the United Kingdom who were mostly general adult
      psychiatrists, child and adolescent psychiatrists, or psychiatrists with an
      interest in eating disorders. RESULTS: Respondents generally supported a role for
      compulsory measures under mental health legislation in the treatment of patients
      with anorexia nervosa. Compared to 'mild' anorexia nervosa, respondents generally
      were less likely to feel that patients with 'severe' anorexia nervosa were
      intentionally engaging in weight loss behaviours, were able to control their
      behaviours, wanted to get better, or were able to reason properly. However,
      eating disorder specialists were less likely than other psychiatrists to think
      that patients with 'mild' anorexia nervosa were choosing to engage in their
      behaviours or able to control their behaviours. Child and adolescent
      psychiatrists were more likely to have a positive view of the use of parental
      consent and compulsory treatment for an adolescent with anorexia nervosa. Three
      factors emerged from factor analysis of the responses named: 'Support for the
      powers of the Mental Health Act to protect from harm'; 'Primacy of best
      interests'; and 'Autonomy viewed as being preserved in anorexia nervosa'.
      Different scores on these factor scales were given in terms of type of specialist
      and gender. CONCLUSION: In general, senior psychiatrists tend to support the use
      of compulsory treatment to protect the health of patients at risk and also to
      protect the welfare of patients in their best interests. In particular, eating
      disorder specialists tend to support the compulsory treatment of patients with
      anorexia nervosa independently of views about their decision-making capacity,
      while child and adolescent psychiatrists tend to support the treatment of
      patients with anorexia nervosa in their best interests where decision-making is
      impaired.

PMID- 19091114
TI  - Costs and consequences of large-scale vector control for malaria.
AB  - BACKGROUND: Five large insecticide-treated net (ITN) programmes and two indoor
      residual spraying (IRS) programmes were compared using a standardized costing
      methodology. METHODS: Costs were measured locally or derived from existing
      studies and focused on the provider perspective, but included the direct costs of
      net purchases by users, and are reported in 2005 USD. Effectiveness was estimated
      by combining programme outputs with standard impact indicators. FINDINGS:
      Conventional ITNs: The cost per treated net-year of protection ranged from USD
      1.21 in Eritrea to USD 6.05 in Senegal. The cost per child death averted ranged
      from USD 438 to USD 2,199 when targeting to children was successful.Long-lasting
      insecticidal nets (LLIN) of five years duration: The cost per treated-net year of
      protection ranged from USD 1.38 in Eritrea to USD 1.90 in Togo. The cost per
      child death averted ranged from USD 502 to USD 692.IRS: The costs per person-year
      of protection for all ages were USD 3.27 in KwaZulu Natal and USD 3.90 in
      Mozambique. If only children under five years of age were included in the
      denominator the cost per person-year of protection was higher: USD 23.96 and USD
      21.63. As a result, the cost per child death averted was higher than for ITNs:
      USD 3,933-4,357. CONCLUSION: Both ITNs and IRS are highly cost-effective vector
      control strategies. Integrated ITN free distribution campaigns appeared to be the
      most efficient way to rapidly increase ITN coverage. Other approaches were as or
      more cost-effective, and appeared better suited to "keep-up" coverage levels.
      ITNs are more cost-effective than IRS for highly endemic settings, especially if
      high ITN coverage can be achieved with some demographic targeting.

PMID- 19091115
TI  - Long-term actions of interleukin-1beta on delay and tonic firing neurons in rat
      superficial dorsal horn and their relevance to central sensitization.
AB  - BACKGROUND: Cytokines such as interleukin 1beta (IL-1beta) have been implicated
      in the development of central sensitization that is characteristic of neuropathic
      pain. To examine its long-term effect on nociceptive processing, defined medium
      organotypic cultures of rat spinal cord were exposed to 100 pM IL-1beta for 6-8
      d. Interleukin effects in the dorsal horn were examined by whole-cell patch-clamp
      recording and Ca(2+) imaging techniques. RESULTS: Examination of the cultures
      with confocal Fluo-4 AM imaging showed that IL-1beta increased the change in
      intracellular Ca(2+) produced by exposure to 35-50 mM K+. This is consistent with
      a modest increase in overall dorsal horn excitability. Despite this, IL-1beta did
      not have a direct effect on rheobase or resting membrane potential nor did it
      selectively destroy any specific neuronal population. All effects were instead
      confined to changes in synaptic transmission. A variety of pre- and postsynaptic
      actions of IL-1beta were seen in five different electrophysiologically-defined
      neuronal phenotypes. In putative excitatory 'delay' neurons, cytokine treatment
      increased the amplitude of spontaneous EPSC's (sEPSC) and decreased the frequency
      of spontaneous IPSC's (sIPSC). These effects would be expected to increase dorsal
      horn excitability and to facilitate the transfer of nociceptive information.
      However, other actions of IL-1beta included disinhibition of putative inhibitory
      'tonic' neurons and an increase in the amplitude of sIPSC's in 'delay' neurons.
      CONCLUSION: Since spinal microglial activation peaks between 3 and 7 days after
      the initiation of chronic peripheral nerve injury and these cells release IL
      1beta at this time, our findings define some of the neurophysiological mechanisms
      whereby nerve-injury induced release of IL-1beta may contribute to the central
      sensitization associated with chronic neuropathic pain.

PMID- 19091116
TI  - Genomic analysis of bacteriophage epsilon 34 of Salmonella enterica serovar
      Anatum (15+).
AB  - BACKGROUND: The presence of prophages has been an important variable in genetic
      exchange and divergence in most bacteria. This study reports the determination of
      the genomic sequence of Salmonella phage epsilon 34, a temperate bacteriophage
      that was important in the early study of prophages that modify their hosts' cell
      surface and is of a type (P22-like) that is common in Salmonella genomes.
      RESULTS: The sequence shows that epsilon 34 is a mosaically related member of the
      P22 branch of the lambdoid phages. Its sequence is compared with the known P22
      like phages and several related but previously unanalyzed prophage sequences in
      reported bacterial genome sequences. CONCLUSION: These comparisons indicate that
      there has been little if any genetic exchange within the procapsid assembly gene
      cluster with P22-like E. coli/Shigella phages that are have orthologous but
      divergent genes in this region. Presumably this observation reflects the fact
      that virion assembly proteins interact intimately and divergent proteins can no
      longer interact. On the other hand, non-assembly genes in the "ant moron" appear
      to be in a state of rapid flux, and regulatory genes outside the assembly gene
      cluster have clearly enjoyed numerous and recent horizontal exchanges with phages
      outside the P22-like group. The present analysis also shows that epsilon 34
      harbors a gtrABC gene cluster which should encode the enzymatic machinery to
      chemically modify the host O antigen polysaccharide, thus explaining its ability
      to alter its host's serotype. A comprehensive comparative analysis of the known
      phage gtrABC gene clusters shows that they are highly mobile, having been
      exchanged even between phage types, and that most "bacterial" gtrABC genes lie in
      prophages that vary from being largely intact to highly degraded. Clearly,
      temperate phages are very major contributors to the O-antigen serotype of their
      Salmonella hosts.

PMID- 19091117
TI  - Contact Heat Evoked Potentials Using Simultaneous Eeg And Fmri And Their
      Correlation With Evoked Pain.
AB  - BACKGROUND: The Contact Heat Evoked Potential Stimulator (CHEPS) utilises rapidly
      delivered heat pulses with adjustable peak temperatures to stimulate the
      differential warm/heat thresholds of receptors expressed by Adelta and C fibres.
      The resulting evoked potentials can be recorded and measured, providing a useful
      clinical tool for the study of thermal and nociceptive pathways. Concurrent
      recording of contact heat evoked potentials using electroencephalogram (EEG) and
      functional magnetic resonance imaging (fMRI) has not previously been reported
      with CHEPS. Developing simultaneous EEG and fMRI with CHEPS is highly desirable,
      as it provides an opportunity to exploit the high temporal resolution of EEG and
      the high spatial resolution of fMRI to study the reaction of the human brain to
      thermal and nociceptive stimuli. METHODS: In this study we have recorded evoked
      potentials stimulated by 51 degrees  C contact heat pulses from CHEPS using EEG,
      under normal conditions (baseline), and during continuous and simultaneous
      acquisition of fMRI images in ten healthy volunteers, during two sessions. The
      pain evoked by CHEPS was recorded on a Visual Analogue Scale (VAS). RESULTS:
      Analysis of EEG data revealed that the latencies and amplitudes of evoked
      potentials recorded during continuous fMRI did not differ significantly from
      baseline recordings. fMRI results were consistent with previous thermal pain
      studies, and showed Blood Oxygen Level Dependent (BOLD) changes in the insula,
      post-central gyrus, supplementary motor area (SMA), middle cingulate cortex and
      pre-central gyrus. There was a significant positive correlation between the
      evoked potential amplitude (EEG) and the psychophysical perception of pain on the
      VAS. CONCLUSION: The results of this study demonstrate the feasibility of
      recording contact heat evoked potentials with EEG during continuous and
      simultaneous fMRI. The combined use of the two methods can lead to identification
      of distinct patterns of brain activity indicative of pain and pro-nociceptive
      sensitisation in healthy subjects and chronic pain patients. Further studies are
      required for the technique to progress as a useful tool in clinical trials of
      novel analgesics.

PMID- 19091118
TI  - The prognostic value of blood lactate levels relative to that of vital signs in
      the pre-hospital setting: a pilot study.
AB  - INTRODUCTION: A limitation of pre-hospital monitoring is that vital signs often
      do not change until a patient is in a critical stage. Blood lactate levels are
      suggested as a more sensitive parameter to evaluate a patient's condition. The
      aim of this pilot study was to find presumptive evidence for a relation between
      pre-hospital lactate levels and in-hospital mortality, corrected for vital sign
      abnormalities. METHODS: In this prospective observational study (n = 124),
      patients who required urgent ambulance dispatching and had a systolic blood
      pressure below 100 mmHg, a respiratory rate less than 10 or more than 29
      breaths/minute, or a Glasgow Coma Scale (GCS) below 14 were enrolled. Nurses from
      Emergency Medical Services measured capillary or venous lactate levels using a
      hand-held device on arrival at the scene (T1) and just before or on arrival at
      the emergency department (T2). The primary outcome measured was in-hospital
      mortality. RESULTS: The average (standard deviation) time from T1 to T2 was 27
      (10) minutes. Non-survivors (n = 32, 26%) had significantly higher lactate levels
      than survivors at T1 (5.3 vs 3.7 mmol/L) and at T2 (5.4 vs 3.2 mmol/L). Mortality
      was significantly higher in patients with lactate levels of 3.5 mmol/L or higher
      compared with those with lactate levels below 3.5 mmol/L (T1: 41 vs 12% and T2:
      47 vs 15%). Also in the absence of hypotension, mortality was higher in those
      with higher lactate levels. In a multivariable Cox proportional hazard analysis
      including systolic blood pressure, heart rate, GCS (all at T1) and delta lactate
      level (from T1 to T2), only delta lactate level (hazard ratio (HR) = 0.20, 95%
      confidence interval (CI) = 0.05 to 0.76, p = 0.018) and GCS (HR = 0.93, 95% CI =
      0.88 to 0.99, p = 0.022) were significant independent predictors of in-hospital
      mortality. CONCLUSIONS: In a cohort of patients that required urgent ambulance
      dispatching, pre-hospital blood lactate levels were associated with in-hospital
      mortality and provided prognostic information superior to that provided by the
      patient's vital signs. There is potential for early detection of occult shock and
      pre-hospital resuscitation guided by lactate measurement. However, external
      validation is required before widespread implementation of lactate measurement in
      the out-of-hospital setting.

PMID- 19091119
TI  - Barcodes for genomes and applications.
AB  - BACKGROUND: Each genome has a stable distribution of the combined frequency for
      each k-mer and its reverse complement measured in sequence fragments as short as
      1000 bps across the whole genome, for 1<k<6. The collection of these k-mer
      frequency distributions is unique to each genome and termed the genome's barcode.
      RESULTS: We found that for each genome, the majority of its short sequence
      fragments have highly similar barcodes while sequence fragments with different
      barcodes typically correspond to genes that are horizontally transferred or
      highly expressed. This observation has led to new and more effective ways for
      addressing two challenging problems: metagenome binning problem and
      identification of horizontally transferred genes. Our barcode-based metagenome
      binning algorithm substantially improves the state of the art in terms of both
      binning accuracies and the scope of applicability. Other attractive properties of
      genomes barcodes include (a) the barcodes have different and identifiable
      characteristics for different classes of genomes like prokaryotes, eukaryotes,
      mitochondria and plastids, and (b) barcodes similarities are generally
      proportional to the genomes' phylogenetic closeness. CONCLUSION: These and other
      properties of genomes barcodes make them a new and effective tool for studying
      numerous genome and metagenome analysis problems.

PMID- 19091120
TI  - Evaluation of SOFA-based models for predicting mortality in the ICU: A systematic
      review.
AB  - INTRODUCTION: To systematically review studies evaluating the performance of
      Sequential Organ Failure Assessment (SOFA)-based models for predicting mortality
      in patients in the intensive care unit (ICU). METHODS: Medline, EMBASE and other
      databases were searched for English-language articles with the major objective of
      evaluating the prognostic performance of SOFA-based models in predicting
      mortality in surgical and/or medical ICU admissions. The quality of each study
      was assessed based on a quality framework for prognostic models. RESULTS:
      Eighteen articles met all inclusion criteria. The studies differed widely in the
      SOFA derivatives used and in their methods of evaluation. Ten studies reported
      about developing a probabilistic prognostic model, only five of which used an
      independent validation data set. The other studies used the SOFA-based score
      directly to discriminate between survivors and non-survivors without fitting a
      probabilistic model. In five of the six studies, admission-based models (Acute
      Physiology and Chronic Health Evaluation (APACHE) II/III) were reported to have a
      slightly better discrimination ability than SOFA-based models at admission (the
      receiver operating characteristic curve (AUC) of SOFA-based models ranged between
      0.61 and 0.88), and in one study a SOFA model had higher AUC than the Simplified
      Acute Physiology Score (SAPS) II model. Four of these studies used the Hosmer
      Lemeshow tests for calibration, none of which reported a lack of fit for the SOFA
      models. Models based on sequential SOFA scores were described in 11 studies
      including maximum SOFA scores and maximum sum of individual components of the
      SOFA score (AUC range: 0.69 to 0.92) and delta SOFA (AUC range: 0.51 to 0.83).
      Studies comparing SOFA with other organ failure scores did not consistently show
      superiority of one scoring system to another. Four studies combined SOFA-based
      derivatives with admission severity of illness scores, and they all reported on
      improved predictions for the combination. Quality of studies ranged from 11.5 to
      19.5 points on a 20-point scale. CONCLUSIONS: Models based on SOFA scores at
      admission had only slightly worse performance than APACHE II/III and were
      competitive with SAPS II models in predicting mortality in patients in the
      general medical and/or surgical ICU. Models with sequential SOFA scores seem to
      have a comparable performance with other organ failure scores. The combination of
      sequential SOFA derivatives with APACHE II/III and SAPS II models clearly
      improved prognostic performance of either model alone. Due to the heterogeneity
      of the studies, it is impossible to draw general conclusions on the optimal
      mathematical model and optimal derivatives of SOFA scores. Future studies should
      use a standard evaluation methodology with a standard set of outcome measures
      covering discrimination, calibration and accuracy.

PMID- 19091121
TI  - Desmoglein 2 is a substrate of kallikrein 7 in pancreatic cancer.
AB  - BACKGROUND: In a previous report we have demonstrated that the chymotryptic-like
      serine protease kallikrein 7 (KLK7/hK7) is overexpressed in pancreatic cancer. In
      normal skin, hK7 is thought to participate in skin desquamation by contributing
      in the degradation of desmosomal components, such as desmogleins. Thus, the
      ability of hK7 to degrade desmogleins was assessed and the effect of hK7
      expression on desmoglein 2 was examined in cultured pancreatic cancer cells.
      METHODS: The expression of Dsg1, Dsg2, and Dsg3 in pancreatic tissues was
      examined by immunohistochemistry and their expression in two pancreatic cancer
      cell lines, BxPC-3 and Panc-1, was determined by western blot analysis. The
      ability of hK7 to degrade Dsg1 and Dsg2 was investigated using in vitro
      degradation assays. BxPC-3 cells stably transfected to overexpress hK7 were used
      to examine the effect of hK7 on cell-surface resident Dsg2. RESULTS: The levels
      of immunoreactive Dsg1 and Dsg2 were reduced in pancreatic adenocarcinomas
      compared with both normal pancreatic and chronic pancreatitis tissues. Among the
      desmosomal proteins examined, Dsg2 exhibited robust expression on the surface of
      BxPC-3 cells. When hK7 was overexpressed in this cell line, there was a
      significant increase in the amount of soluble Dsg2 released into the culture
      medium compared with vector-transfected control cells. CONCLUSION: A reduction in
      the amount of the cell adhesion components Dsg1 and Dsg2 in pancreatic tumors
      suggests that loss of these desmosomal proteins may play a role in pancreatic
      cancer invasion. Using in vitro degradation assays, both Dsg1 and Dsg2 could be
      readily proteolyzed by hK7, which is overexpressed in pancreatic adenocarcinomas.
      The enforced expression of hK7 in BxPC-3 cells that express significant amounts
      of Dsg2 resulted in a marked increase in the shedding of soluble Dsg2, which is
      consistent with the notion that aberrant expression of hK7 in pancreatic tumors
      may result in diminished cell-cell adhesion and facilitate tumor cell invasion.

PMID- 19091122
TI  - Evidence from glycine transfer RNA of a frozen accident at the dawn of the
      genetic code.
AB  - BACKGROUND: Transfer RNA (tRNA) is the means by which the cell translates DNA
      sequence into protein according to the rules of the genetic code. A credible
      proposition is that tRNA was formed from the duplication of an RNA hairpin half
      the length of the contemporary tRNA molecule, with the point at which the
      hairpins were joined marked by the canonical intron insertion position found
      today within tRNA genes. If these hairpins possessed a 3'-CCA terminus with
      different combinations of stem nucleotides (the ancestral operational RNA code),
      specific aminoacylation and perhaps participation in some form of noncoded
      protein synthesis might have occurred. However, the identity of the first tRNA
      and the initial steps in the origin of the genetic code remain elusive. RESULTS:
      Here we show evidence that glycine tRNA was the first tRNA, as revealed by a
      vestigial imprint in the anticodon loop sequences of contemporary descendents.
      This provides a plausible mechanism for the missing first step in the origin of
      the genetic code. In 448 of 466 glycine tRNA gene sequences from bacteria,
      archaea and eukaryote cytoplasm analyzed, CCA occurs immediately upstream of the
      canonical intron insertion position, suggesting the first anticodon (NCC for
      glycine) has been captured from the 3'-terminal CCA of one of the interacting
      hairpins as a result of an ancestral ligation. CONCLUSION: That this imprint
      (including the second and third nucleotides of the glycine tRNA anticodon) has
      been retained through billions of years of evolution suggests Crick's 'frozen
      accident' hypothesis has validity for at least this very first step at the dawn
      of the genetic code. REVIEWERS: This article was reviewed by Dr Eugene V. Koonin,
      Dr Rob Knight and Dr David H Ardell.

PMID- 19091123
TI  - Adrenocortical oncocytic carcinoma with recurrent metastases: a case report and
      review of the literature.
AB  - BACKGROUND: Adrenal cortex oncocytic carcinoma (AOC) represents an exceptional
      pathological entity, since only 22 cases have been documented in the literature
      so far. CASE PRESENTATION: Our case concerns a 54-year-old man with past medical
      history of right adrenal excision with partial hepatectomy, due to an
      adrenocortical carcinoma. The patient was admitted in our hospital to undergo
      surgical resection of a left lung mass newly detected on chest Computed
      Tomography scan. The histological and immunohistochemical study revealed a
      metastatic AOC. Although the patient was given mitotane orally in adjuvant basis,
      he experienced relapse with multiple metastases in the thorax twice in the next
      year and was treated with consecutive resections. Two and a half years later, a
      right hip joint metastasis was found and concurrent chemoradiation was given.
      Finally, approximately five years post disease onset, the patient died due to
      massive metastatic disease. A thorough review of AOC and particularly all
      diagnostic difficulties are extensively stated. CONCLUSION: Histological
      classification of adrenocortical oncocytic tumours has been so far a matter of
      debate. There is no officially established histological scoring system regarding
      these rare neoplasms and therefore many diagnostic difficulties occur for
      pathologists.

PMID- 19091124
TI  - Television, physical activity, diet, and body weight status: the ARIC cohort.
AB  - BACKGROUND: Television (TV) watching is the most common leisure activity in the
      United States. Few studies of adults have described the relationship between TV
      and health behaviors such as physical activity, diet, and body weight status.
      METHODS: Extant data from the Atherosclerosis Risk in Communities (ARIC) Study
      were analyzed to assess the association of TV with physical activity, diet, and
      body mass index (BMI) among 15,574 adults at baseline (1986-89) and 12,678 adults
      six years later. Television, physical activity, and diet were collected with
      questionnaires and BMI was measured at both time points. Based on baseline TV
      exposure, adults were categorized into high, medium, and low TV exposure. Linear
      and logistic regression models were adjusted for gender, age, race-center,
      smoking, education, and general health. RESULTS: Relative to participants who had
      low TV exposure, those with high TV exposure were more likely to be less
      physically active and have a poorer dietary profile at baseline and six-years
      later. Participants with high TV exposure at baseline had a 40% and 31% greater
      odds of being considered insufficiently active at baseline (1.40, 95% CI 1.26,
      1.55), and six years later (1.31, 95% CI 1.18, 1.46). At baseline, high TV
      exposure was also associated with a 20% to 30% greater odds of being above the
      median for servings of salty snacks (1.37, 95% CI 1.24, 1.51), sweets (1.26, 95%
      CI 1.15, 1.38), and sweetened drinks (1.29, 95% CI 1.17, 1.42), and below the
      median for fruit and vegetable servings (1.36, 95% CI 1.24, 1.50). Higher TV
      exposure was also cross-sectionally associated with a greater odds for being
      overweight or obese (1.43, 95% CI 1.29, 1.58). Similar associations were observed
      between baseline TV exposure and six-year physical activity and diet, but were
      not observed with BMI after six years follow-up. CONCLUSION: These results
      support the hypothesis that time spent watching TV is associated with deleterious
      effects on physical activity, diet, and BMI.

PMID- 19091125
TI  - Avian reovirus L2 genome segment sequences and predicted structure/function of
      the encoded RNA-dependent RNA polymerase protein.
AB  - BACKGROUND: The orthoreoviruses are infectious agents that possess a genome
      comprised of 10 double-stranded RNA segments encased in two concentric protein
      capsids. Like virtually all RNA viruses, an RNA-dependent RNA polymerase (RdRp)
      enzyme is required for viral propagation. RdRp sequences have been determined for
      the prototype mammalian orthoreoviruses and for several other closely-related
      reoviruses, including aquareoviruses, but have not yet been reported for any
      avian orthoreoviruses. RESULTS: We determined the L2 genome segment nucleotide
      sequences, which encode the RdRp proteins, of two different avian reoviruses,
      strains ARV138 and ARV176 in order to define conserved and variable regions
      within reovirus RdRp proteins and to better delineate structure/function of this
      important enzyme. The ARV138 L2 genome segment was 3829 base pairs long, whereas
      the ARV176 L2 segment was 3830 nucleotides long. Both segments were predicted to
      encode lambdaB RdRp proteins 1259 amino acids in length. Alignments of these
      newly-determined ARV genome segments, and their corresponding proteins, were
      performed with all currently available homologous mammalian reovirus (MRV) and
      aquareovirus (AqRV) genome segment and protein sequences. There was approximately
      55% amino acid identity between ARV lambdaB and MRV lambda3 proteins, making the
      RdRp protein the most highly conserved of currently known orthoreovirus proteins,
      and there was approximately 28% identity between ARV lambdaB and homologous MRV
      and AqRV RdRp proteins. Predictive structure/function mapping of identical and
      conserved residues within the known MRV lambda3 atomic structure indicated most
      identical amino acids and conservative substitutions were located near and within
      predicted catalytic domains and lining RdRp channels, whereas non-identical amino
      acids were generally located on the molecule's surfaces. CONCLUSION: The ARV
      lambdaB and MRV lambda3 proteins showed the highest ARV:MRV identity values
      (approximately 55%) amongst all currently known ARV and MRV proteins. This
      implies significant evolutionary constraints are placed on dsRNA RdRp molecules,
      particularly in regions comprising the canonical polymerase motifs and residues
      thought to interact directly with template and nascent mRNA. This may point the
      way to improved design of anti-viral agents specifically targeting this enzyme.

PMID- 19091126
TI  - Identifying people at high risk for developing sleep apnea syndrome (SAS): a
      cross-sectional study in a Pakistani population.
AB  - BACKGROUND: Obstructive Sleep Apnea (OSA) is associated with many cardiovascular
      and psychiatric diseases. Day-time sleepiness is a common consequence of sleep
      apnea and correlates with road-traffic accidents (RTA). Pakistan has a high
      prevalence of factors which predispose an individual to OSA and death from RTAs
      are a huge burden. However there is a dearth of prevalence studies in this
      regard. We aim to understand local relevance of the disease and estimate the
      prevalence of individuals high-risk for OSA. METHODS: This cross-sectional survey
      was conducted among 450 individuals at Aga Khan University Hospital (AKUH), which
      is a tertiary care teaching hospital in Pakistan. We used the BQ as our
      measurement tool. Based on the responses, participants were grouped into high or
      low-risk for OSA. RESULTS: Our study sample size was 418 with 63.2% males. Mean
      age of our study population was 30.4 SD+/-12.3 years; and mean BMI was 23.2 SD+/
      5 kg/m2. Out of the total sample size 24.9% reported snoring and there were twice
      as many males who snored as compared to females. Forty-five individuals reported
      that they had nodded off to sleep while driving at least once in their lifetime.
      On the other hand, the highest proportion of high risk individuals 47.6% was
      found in the age group 60 or above. The overall prevalence of individuals who
      were high risk for sleep apnea was 10%. CONCLUSION: A significant proportion of
      the population is at high-risk for OSA. Our study shows that despite low BMI and
      favorable craniofacial anatomy sleep apnea is still a locally relevant disease.
      Given the local relevance of OSAS, it is important to increase awareness among
      general population but more importantly among physicians of the developing
      countries, like Pakistan, about common clinical features and pertinent risk
      factors and complications of OSAS.

PMID- 19091127
TI  - Astaxanthin vs placebo on arterial stiffness, oxidative stress and inflammation
      in renal transplant patients (Xanthin): a randomised controlled trial.
AB  - BACKGROUND: There is evidence that renal transplant recipients have accelerated
      atherosclerosis manifest by increased cardiovascular morbidity and mortality. The
      high incidence of atherosclerosis is, in part, related to increased arterial
      stiffness, vascular dysfunction, elevated oxidative stress and inflammation
      associated with immunosuppressive therapy. The dietary supplement astaxanthin has
      shown promise as an antioxidant and anti-inflammatory therapeutic agent in
      cardiovascular disease. The aim of this trial is to investigate the effects of
      astaxanthin supplementation on arterial stiffness, oxidative stress and
      inflammation in renal transplant patients. METHOD AND DESIGN: This is a
      randomised, placebo controlled clinical trial. A total of 66 renal transplant
      recipients will be enrolled and allocated to receive either 12 mg/day of
      astaxanthin or an identical placebo for one-year. Patients will be stratified
      into four groups according to the type of immunosuppressant therapy they receive:
      1) cyclosporine, 2) sirolimus, 3) tacrolimus or 4) prednisolone+/-azathioprine,
      mycophenolate mofetil or mycophenolate sodium. Primary outcome measures will be
      changes in 1) arterial stiffness measured by aortic pulse wave velocity (PWV), 2)
      oxidative stress assessed by plasma isoprostanes and 3) inflammation by plasma
      pentraxin 3. Secondary outcomes will include changes in vascular function
      assessed using the brachial artery reactivity (BAR) technique, carotid artery
      intimal medial thickness (CIMT), augmentation index (AIx), left ventricular
      afterload and additional measures of oxidative stress and inflammation. Patients
      will undergo these measures at baseline, six and 12 months. DISCUSSION: The
      results of this study will help determine the efficacy of astaxanthin on vascular
      structure, oxidative stress and inflammation in renal transplant patients. This
      may lead to a larger intervention trial assessing cardiovascular morbidity and
      mortality. TRIAL REGISTRATION: ACTRN12608000159358.

PMID- 19091128
TI  - Human immunodeficiency virus type-1 reverse transcriptase exists as post
      translationally modified forms in virions and cells.
AB  - BACKGROUND: HIV-1 reverse transcriptase (RT) is a heterodimer composed of p66 and
      p51 subunits and is responsible for reverse transcription of the viral RNA genome
      into DNA. RT can be post-translationally modified in vitro which may be an
      important mechanism for regulating RT activity. Here we report detection of
      different p66 and p51 RT isoforms by 2D gel electrophoresis in virions and
      infected cells. RESULTS: Major isoforms of the p66 and p51 RT subunits were
      observed, with pI's of 8.44 and 8.31 respectively (p66(8.44) and p51(8.31)). The
      same major isoforms were present in virions, virus-infected cell lysates and
      intracellular reverse transcription complexes (RTCs), and their presence in RTCs
      suggested that these are likely to be the forms that function in reverse
      transcription. Several minor RT isoforms were also observed. The observed pIs of
      the RT isoforms differed from the pI of theoretical unmodified RT (p66(8.53) and
      p51(8.60)), suggesting that most of the RT protein in virions and cells is post
      translationally modified. The modifications of p66(8.44) and p51(8.31) differed
      from each other indicating selective modification of the different RT subunits.
      The susceptibility of RT isoforms to phosphatase treatment suggested that some of
      these modifications were due to phosphorylation. Dephosphorylation, however, had
      no effect on in vitro RT activity associated with virions, infected cells or RTCs
      suggesting that the phospho-isoforms do not make a major contribution to RT
      activity in an in vitro assay. CONCLUSION: The same major isoform of p66 and p51
      RT is found in virions, infected cells and RTC's and both of these subunits are
      post-translationally modified. This post-translational modification of RT may be
      important for the function of RT inside the cell.

PMID- 19091129
TI  - Gemcitabine-based versus fluoropyrimidine-based chemotherapy with or without
      platinum in unresectable biliary tract cancer: a retrospective study.
AB  - BACKGROUND: There is no standard palliative chemotherapy regimen in biliary tract
      cancers (BTC). Fluoropyrimidine or gemcitabine, with or without platinum, are
      most frequently used. We conducted this study to clarify the efficacy of
      palliative chemotherapy in BTC. METHODS: Patients with unresectable BTC treated
      with palliative chemotherapy between Oct 2001 and Aug 2006 at Seoul National
      University Hospital were reviewed retrospectively. Histologically confirmed cases
      of intrahepatic cholangiocarcinoma, gallbladder cancer, extrahepatic bile duct
      cancer, and ampulla of Vater carcinoma were enrolled. We analyzed the efficacy of
      regimens: gemcitabine (G) versus fluoropyrimidine (F) and with or without
      platinum (P). RESULTS: A total of 243 patients were enrolled. 159 patients (65%)
      were male and the median age of the patients was 60 years (range 26-81).
      Intrahepatic cholangiocarcinoma, gallbladder cancer, extrahepatic bile duct
      cancer, and ampulla of Vater carcinoma were 92, 72, 58, and 21 cases,
      respectively. The median progression free survival (PFS) was 4.3 months (95% CI,
      3.7-4.9) and median overall survival (OS) was 8.7 months (95% CI, 7.4-10.0).
      Ninety-nine patients received G-based chemotherapy (94 GP, 5 G alone), and 144
      patients received F-based chemotherapy (83 FP, 61 F alone). The response rate
      (RR), disease control rate (DCR), PFS and OS of G-based chemotherapy versus F
      based chemotherapy were 16.7% vs. 19.5% (P=0.591), 52.8% vs. 58.9% (P=0.372), 4.0
      months vs. 4.3 months (P=0.816), and 7.8 months vs. 9.1 months (P=0.848),
      respectively. Sixty-six patients received F or G without P, and 177 patients
      received F or G with P. The RR, DCR, PFS and OS of chemotherapy without P versus
      chemotherapy including P were 12.7% vs. 20.6% (P=0.169), 46.0% vs. 60.6%
      (P=0.049), 3.3 months vs. 4.4 months (P=0.887), and 10.6 months vs. 8.1 months
      (P=0.257), respectively. CONCLUSION: In unresectable BTC, F-based and G-based
      chemotherapy showed similar efficacy in terms of RR, DCR, PFS and OS. The benefit
      of adding P to F or G was not significant except for DCR. Further prospective
      studies which define the efficacy of various chemotherapeutic regimens in BTC are
      warranted.

PMID- 19091130
TI  - Similar rates of protein adaptation in Drosophila miranda and D. melanogaster,
      two species with different current effective population sizes.
AB  - BACKGROUND: Adaptive protein evolution is common in several Drosophila species
      investigated. Some studies point to very weak selection operating on amino-acid
      mutations, with average selection intensities on the order of Nes approximately
      in D. melanogaster and D. simulans. Species with lower effective population sizes
      should undergo less adaptation since they generate fewer mutations and selection
      is ineffective on a greater proportion of beneficial mutations. RESULTS: Here I
      study patterns of polymorphism and divergence at 91 X-linked loci in D. miranda,
      a species with a roughly 5-fold smaller effective population size than D.
      melanogaster. Surprisingly, I find a similar fraction of amino-acid mutations
      being driven to fixation by positive selection in D. miranda and D. melanogaster.
      Genes with higher rates of amino-acid evolution show lower levels of neutral
      diversity, a pattern predicted by recurrent adaptive protein evolution. I fit a
      hitchhiking model to patterns of polymorphism in D. miranda and D. melanogaster
      and estimate an order of magnitude higher selection coefficients for beneficial
      mutations in D. miranda. CONCLUSION: This analysis suggests that effective
      population size may not be a major determinant in rates of protein adaptation.
      Instead, adaptation may not be mutation-limited, or the distribution of fitness
      effects for beneficial mutations might differ vastly between different species or
      populations. Alternative explanation such as biases in estimating the fraction of
      beneficial mutations or slightly deleterious mutation models are also discussed.

PMID- 19091132
TI  - Advanced gastric cancer showing long-term complete remission in response to S-1
      monotherapy: two case reports.
AB  - We herein report two cases showing long-term complete remission (CR) in response
      to S-1 monotherapy. Case 1 was a 65-year-old male diagnosed with an advanced
      poorly differentiated adenocarcinoma of the stomach with paraaortic lymph node
      metastases, which disappeared after S-1 monotherapy. Subsequently a total
      gastrectomy was performed, and histological CR was evident. His progress is
      presently uneventful without recurrence 50 months after surgery. Case 2 was a 59
      year-old female who underwent a total gastrectomy with a jejunal pouch. The
      resected tumor was a medullary type poorly differentiated adenocarcinoma
      infiltrating the serosa and involving the regional lymph nodes. One year after
      surgery, endoscopy revealed a recurrent tumor in the jejunal pouch. After the
      administration of S-1, this recurrent tumor completely disappeared, and she has
      since maintained CR for 39 months. These cases suggest that a subgroup of
      patients with advanced gastric cancer may attain CR with S-1 monotherapy.

PMID- 19091131
TI  - Increased p38-MAPK is responsible for chemotherapy resistance in human gastric
      cancer cells.
AB  - BACKGROUND: Chemoresistance is one of the main obstacles to successful cancer
      therapy and is frequently associated with Multidrug resistance (MDR). Many
      different mechanisms have been suggested to explain the development of an MDR
      phenotype in cancer cells. One of the most studied mechanisms is the
      overexpression of P-glycoprotein (P-gp), which is a product of the MDR1 gene.
      Tumor cells often acquire the drug-resistance phenotype due to upregulation of
      the MDR1 gene. Overexpression of MDR1 gene has often been reported in primary
      gastric adenocarcinoma. METHODS: This study investigated the role of p38-MAPK
      signal pathway in vincristine-resistant SGC7901/VCR cells. P-gp and MDR1 RNA were
      detected by Western blot analysis and RT-PCR amplification. Mitgen-activated
      protein kinases and function of P-gp were demonstrated by Western blot and FACS
      Aria cytometer analysis. Ap-1 activity and cell apoptosis were detected by Dual
      Luciferase Reporter Assay and annexin V-PI dual staining. RESULTS: The
      vincristine-resistant SGC7901/VCR cells with increased expression of the
      multidrug-resistance 1 (MDR1) gene were resistant to P-gp-related drug and P-gp
      unrelated drugs. Constitutive increases of phosphorylated p38-MAPK and AP-1
      activities were also found in the drug-resistant cells. Inhibition of p38-MAPK by
      SB202190 reduced activator protein-1 (AP-1) activity and MDR1 expression levels
      and increased the sensitivity of SGC7901/VCR cells to chemotherapy. CONCLUSION:
      Activation of the p38-MAPK pathway might be responsible for the modulation of P
      glycoprotein-mediated and P-glycoprotein-unmediated multidrug resistance in the
      SGC7901/VCR cell line.

PMID- 19091133
TI  - Gemcitabine combined with oxaliplatin in pretreated patients with malignant
      pleural mesothelioma: an observational study.
AB  - BACKGROUND: The aim of this study was to investigate the efficacy and safety of
      oxaliplatin +/- gemcitabine in patients with diffuse malignant pleural
      mesothelioma (MPM) pretreated with pemetrexed. METHODS: The study enrolled
      consecutive patients with relapsed MPM, all of them pretreated with a platin
      pemetrexed-based chemotherapy. Oxaliplatin 80 mg/m2 was administered as
      monotherapy or in combination with gemcitabine 1000 mg/m2 given on day 1 and 8.
      Cycles were repeated every 21 days. The primary endpoints were response rate and
      disease control rate. Secondary endpoints included overall survival (OS), time to
      tumour progression (TTP), progression-free survival (PFS), time to treatment
      failure (TTF), and toxicity. RESULTS: Between February 2005 and September 2007 29
      patients (median age: 65.0 years, World Health Organisation (WHO) performance
      status: 0-3) were enrolled. The follow-up period encompassed 5.4 to 97.4 weeks
      (median: 24.3 weeks). Out of these 29 patients, 15 were treated in second, 10 in
      third, 3 in fourth and 1 in fifth line, respectively. The majority of the
      patients received the combination oxaliplatin and gemcitabine (n = 25 vs. 4; 86.2
      vs. 13.8%).The median overall survival (OS) was 71.7 weeks (30.6-243.3 weeks),
      whereas survival from the start of oxaliplatin/gemcitabine-treatment was 24.3
      weeks (5.4-97.3 weeks). Median time to tumour progression (TTP) was 9.3 weeks
      (3.0-67.6 weeks).Partial response (PR) was observed in 2 patients (6.9%), stable
      disease (SD) for at least three courses of treatment in 11 patients (37.9%).
      Thus, disease control rate was 44.8%, whereas 16 of 29 patients exhibited
      progressive disease (55.2%).The toxicity profile was favourable, with no WHO
      grade 4-toxicities, only few dose-reductions were performed due to non
      symptomatic haematotoxicities (neutropenia, thrombopenia). Mild WHO grade 2
      neurotoxicity was seen in 6 patients. CONCLUSION: Pemetrexed-pretreated patients
      with progressive MPM may benefit from a consecutive chemotherapy with oxaliplatin
      and gemcitabine without significant toxicity.

PMID- 19091134
TI  - A mixed methods inquiry: How dairy farmers perceive the value(s) of their
      involvement in an intensive dairy herd health management program.
AB  - BACKGROUND: Research has been scarce when it comes to the motivational and
      behavioral sides of farmers' expectations related to dairy herd health management
      programs. The objectives of this study were to explore farmers' expectations
      related to participation in a health management program by: 1) identifying
      important ambitions, goals and subjective well-being among farmers, 2) submitting
      those data to a quantitative analysis thereby characterizing perspective(s) of
      value added by health management programs among farmers; and 3) to characterize
      perceptions of farmers' goals among veterinarians. METHODS: The subject was
      initially explored by means of literature, interviews and discussions with
      farmers, herd health management consultants and researchers to provide an
      understanding (a concourse) of the research entity. The concourse was then broken
      down into 46 statements. Sixteen Danish dairy farmers and 18 veterinarians
      associated with one large nationwide veterinary practice were asked to rank the
      46 statements that defined the concourse. Next, a principal component analysis
      was applied to identify correlated statements and thus families of perspectives
      between respondents. Q-methodology was utilized to represent each of the
      statements by one row and each respondent by one column in the matrix. A subset
      of the farmers participated in a series of semi-structured interviews to face
      validate the concourse and to discuss subjects like animal welfare,
      veterinarians' competences as experienced by the farmers and time constraints in
      the farmers' everyday life. RESULTS: Farmers' views could be described by four
      families of perspectives: Teamwork, Animal welfare, Knowledge dissemination, and
      Production. Veterinarians believed that farmers' primary focus was on production
      and profit, however, farmers' valued teamwork and animal welfare more.
      CONCLUSION: The veterinarians in this study appear to focus too much on financial
      performance and increased production when compared to most of the participating
      farmers' expectations. On the other hand veterinarians did not focus enough on
      the major products, which farmers really wanted to buy, i.e. teamwork and animal
      welfare. Consequently, disciplines like sociology, economics and marketing may
      offer new methodological approaches to veterinarians as these disciplines have
      understood that accounting for individual differences is central to motivate
      change, i.e. 'know thy customer'.

PMID- 19091135
TI  - Visual ecology of the Australian lungfish (Neoceratodus forsteri).
AB  - BACKGROUND: The transition from water to land was a key event in the evolution of
      vertebrates that occurred over a period of 15-20 million years towards the end of
      the Devonian. Tetrapods, including all land-living vertebrates, are thought to
      have evolved from lobe-finned (sarcopterygian) fish that developed adaptations
      for an amphibious existence. However, while many of the biomechanical and
      physiological modifications necessary to achieve this feat have been studied in
      detail, little is known about the sensory adaptations accompanying this
      transition. In this study, we investigated the visual system and visual ecology
      of the Australian lungfish Neoceratodus forsteri, which is the most primitive of
      all the lungfish and possibly the closest living relative to the ancestors of
      tetrapods. RESULTS: Juvenile Neoceratodus have five spectrally distinct retinal
      visual pigments. A single type of rod photoreceptor contains a visual pigment
      with a wavelength of maximum absorbance (lambdamax) at 540 nm. Four spectrally
      distinct single cone photoreceptors contain visual pigments with lambdamax at 366
      (UVS), 479 (SWS), 558 (MWS) and 623 nm (LWS). No double cones were found. Adult
      lungfish do not possess UVS cones and, unlike juveniles, have ocular media that
      prevent ultraviolet light from reaching the retina. Yellow
      ellipsoidal/paraboloidal pigments in the MWS cones and red oil droplets in the
      LWS cones narrow the spectral sensitivity functions of these photoreceptors and
      shift their peak sensitivity to 584 nm and 656 nm, respectively. Modelling of the
      effects of these intracellular spectral filters on the photoreceptor colour space
      of Neoceratodus suggests that they enhance their ability to discriminate objects,
      such as plants and other lungfishes, on the basis of colour. CONCLUSION: The
      presence of a complex colour vision system based on multiple cone types and
      intracellular spectral filters in lungfishes suggests that many of the ocular
      characteristics seen in terrestrial or secondarily aquatic vertebrates, such as
      birds and turtles, may have evolved in shallow water prior to the transition onto
      land. Moreover, the benefits of spectral filters for colour discrimination apply
      equally to purely aquatic species as well as semi-aquatic and terrestrial
      animals. The visual system of the Australian lungfish resembles that of
      terrestrial vertebrates far more closely than that of other sarcopterygian fish.
      This supports the idea that lungfishes, and not the coelacanth, are the closest
      living relatives of the ancestors of tetrapods.

PMID- 19091136
TI  - Outcomes in culture positive and culture negative ascitic fluid infection in
      patients with viral cirrhosis: cohort study.
AB  - BACKGROUND: Ascitic fluid infection (AFI) in cirrhotic patients has a high
      morbidity and mortality. It has two variants namely, spontaneous bacterial
      peritonitis (SBP) and culture negative neutrocytic ascites (CNNA). The aim of
      this study was to determine the outcome in cirrhotic patients with culture
      positive (SBP) and culture negative neutrocytic ascites. METHODS: We analyzed 675
      consecutive hepatitis B and/or C related cirrhosis patients with ascites admitted
      in our hospital from November 2005 to December 2007. Of these, 187 patients had
      AFI; clinical and laboratory parameters of these patients including causes of
      cirrhosis, Child Turcotte Pugh (CTP) score were recorded. RESULTS: Out of 187
      patients with AFI, 44 (23.5%) had SBP while 143 (76.4%) had CNNA. Hepatitis C
      virus (HCV) infection was the most common cause of cirrhosis in 139 (74.3%)
      patients. Patients with SBP had high CTP score as compared to CNNA (12.52 +/-
      1.45 vs. 11.44 +/- 1.66); p < 0.001. Platelets count was low in patients with SBP
      (101 +/- 53 x 10(9)/L) as compared to CNNA (132 +/- 91 x 10(9)/L), p = 0.005. We
      found a high creatinine (mg/dl) (1.95 +/- 1.0 vs. 1.44 +/- 0.85), (p = 0.003) and
      high prothrombin time (PT) in seconds (24.8 +/- 6.6 vs. 22.4 +/- 7.2) (p = 0.04)
      in SBP as compared to CNNA. More patients with SBP (14/44; 31.8%) had blood
      culture positivity as compare to CNNA (14/143; 9.8%), p = 0.002. Escherichia.
      Coli was the commonest organism in blood culture in 15/28 (53.5%) patients. SBP
      group had a higher mortality (11/44; 25%) as compared to CNNA (12/143; 8.4%), p =
      0.003. On multiple logistic regression analysis, creatinine >1.1 mg/dl and
      positive blood culture were the independent predictors of mortality in patients
      with SBP. CONCLUSION: Patients with SBP have a higher mortality than CNNA.
      Independent predictors of mortality in SBP are raised serum creatinine and a
      positive blood culture.

PMID- 19091137
TI  - Cimetidine inhibits salivary gland tumor cell adhesion to neural cells and
      induces apoptosis by blocking NCAM expression.
AB  - BACKGROUND: Cimetidine, a histamine type-2 receptor antagonist, has been reported
      to inhibit the growth of glandular tumors such as colorectal cancer, however the
      mechanism of action underlying this effect is unknown. Adenoid cystic carcinoma
      is well known as a malignant salivary gland tumor which preferentially invades
      neural tissues. We demonstrated previously that human salivary gland tumor (HSG)
      cells spontaneously express neural cell adhesion molecule (NCAM), that HSG cell
      proliferation may be controlled via a homophilic (NCAM-NCAM) binding mechanism
      and that NCAM may be associated with perineural invasion by malignant salivary
      gland tumors. We further demonstrated that cimetidine inhibited NCAM expression
      and induced apoptosis in HSG cells. Here, we investigated the effects of
      cimetidine on growth and perineural/neural invasion of salivary gland tumor
      cells. METHODS: In this study, we have examined the effect of cimetidine on
      cancer cell adhesion to neural cells in vitro, one of the critical steps of
      cancer invasion and metastasis. We have also used an in vivo carcinogenesis model
      to confirm the effect of cimetidine. RESULTS: We have demonstrated for the first
      time that cimetidine can block the adhesion of HSG cells to neural cell
      monolayers and that it can also induce significant apoptosis in the tumor mass in
      a nude mouse model. We also demonstrated that these apoptotic effects of
      cimetidine might occur through down-regulation of the cell surface expression of
      NCAM on HSG cells. Cimetidine-mediated down-regulation of NCAM involved
      suppression of the nuclear translocation of NF-kappaB, a transcriptional
      activator of NCAM gene expression. CONCLUSION: These findings suggest that growth
      and perineural/neural invasion of salivary gland tumors can be blocked by
      administration of cimetidine via induction of apoptosis and in which NCAM plays a
      role.

PMID- 19091139
TI  - From the editors.

PMID- 19091140
TI  - Lessons from the injured brain: a bioethicist in the vineyards of neuroscience.

PMID- 19091138
TI  - Analysis of the role of 13 major fimbrial subunits in colonisation of the chicken
      intestines by Salmonella enterica serovar Enteritidis reveals a role for a novel
      locus.
AB  - BACKGROUND: Salmonella enterica is a facultative intracellular pathogen of
      worldwide importance. Over 2,500 serovars exist and infections in humans and
      animals may produce a spectrum of symptoms from enteritis to typhoid depending on
      serovar- and host-specific factors. S. Enteritidis is the most prevalent non
      typhoidal serovar isolated from humans with acute diarrhoeal illness in many
      countries. Human infections are frequently associated with direct or indirect
      contact with contaminated poultry meat or eggs owing to the ability of the
      organism to persist in the avian intestinal and reproductive tract. The molecular
      mechanisms underlying colonisation of poultry by S. Enteritidis are ill-defined.
      Targeted and genome-wide mutagenesis of S. Typhimurium has revealed conserved and
      host-specific roles for selected fimbriae in intestinal colonisation of different
      hosts. Here we report the first systematic analysis of each chromosomally-encoded
      major fimbrial subunit of S. Enteritidis in intestinal colonisation of chickens.
      RESULTS: The repertoire, organisation and sequence of the fimbrial operons within
      members of S. enterica were compared. No single fimbrial locus could be
      correlated with the differential virulence and host range of serovars by
      comparison of available genome sequences. Fimbrial operons were highly conserved
      among serovars in respect of gene number, order and sequence, with the exception
      of safA. Thirteen predicted major fimbrial subunit genes were separately
      inactivated by lambda Red recombinase-mediated linear recombination followed by
      P22/int transduction. The magnitude and duration of intestinal colonisation by
      mutant and parent strains was measured after oral inoculation of out-bred
      chickens. Whilst the majority of S. Enteritidis major fimbrial subunit genes
      played no significant role in colonisation of the avian intestines, mutations
      affecting pegA in two different S. Enteritidis strains produced statistically
      significant attenuation. Plasmid-mediated trans-complementation partially
      restored the colonisation phenotype. CONCLUSION: We describe the fimbrial gene
      repertoire of the predominant non-typhoidal S. enterica serovar affecting humans
      and the role played by each predicted major fimbrial subunit in intestinal
      colonisation of the primary reservoir. Our data support a role for PegA in the
      colonisation of poultry by S. Enteritidis and aid the design of improved
      vaccines.

PMID- 19091141
TI  - Negative and positive claims of conscience.

PMID- 19091142
TI  - Responsibility and priority in liver transplantation.

PMID- 19091143
TI  - Bioethics and social studies of medicine: overlapping concerns.

PMID- 19091144
TI  - Why can't we all just get along? A comment on Turner's plea to social scientists
      and bioethicists.

PMID- 19091145
TI  - Culture, subjectivity, and the ethics of patient-centered pain care.

PMID- 19091146
TI  - Race-based medicine and justice as recognition: exploring the phenomenon of
      BiDil.

PMID- 19091147
TI  - Editorial. Health and human rights.

PMID- 19091148
TI  - Migration and the human right to health.

PMID- 19091149
TI  - The Health Impact Fund: boosting pharmaceutical innovation without obstructing
      free access.

PMID- 19091150
TI  - The artificial womb: a pilot study considering people's views on the artificial
      womb and ectogenesis in Israel.

PMID- 19091152
TI  - Seasonal changes in host phenotype manipulation by an acanthocephalan: time to be
      transmitted?
AB  - SUMMARY: Many complex life cycle parasites exhibit seasonal transmission between
      hosts. Expression of parasite traits related to transmission, such as the
      manipulation of host phenotype, may peak in seasons when transmission is optimal.
      The acanthocephalan Acanthocephalus lucii is primarily transmitted to its fish
      definitive host in spring. We assessed whether the parasitic alteration of 2
      traits (hiding behaviour and coloration) in the isopod intermediate host was more
      pronounced at this time of year. Refuge use by infected isopods was lower,
      relative to uninfected isopods, in spring than in summer or fall. Infected
      isopods had darker abdomens than uninfected isopods, but this difference did not
      vary between seasons. The level of host alteration was unaffected by exposing
      isopods to different light and temperature regimes. In a group of infected
      isopods kept at 4 degrees C, refuge use decreased from November to May,
      indicating that reduced hiding in spring develops during winter. Keeping isopods
      at 16 degrees C instead of 4 degrees C resulted in higher mortality but not
      accelerated changes in host behaviour. Our results suggest that changes in host
      and/or parasite age, not environmental conditions, underlie the seasonal
      alteration of host behaviour, but further work is necessary to determine if this
      is an adaptive parasite strategy to be transmitted in a particular season.

PMID- 19091153
TI  - Heritability and short-term effects of inbreeding in the progenetic trematode
      Coitocaecum parvum: is there a need for the definitive host?
AB  - SUMMARY: Self-fertilization (or selfing), defined as the fusion of male and
      female reproductive cells originating from the same individual, is the most
      extreme case of inbreeding. Although most hermaphroditic organisms are in
      principle able to self-fertilize, this reproductive strategy is commonly
      associated with a major disadvantage: inbreeding depression. Deleterious effects
      due to the loss of genetic diversity have been documented in numerous organisms
      including parasites. Here we studied the effects of inbreeding depression on the
      offspring of the progenetic trematode Coitocaecum parvum. The parasite can use 2
      alternative life-history strategies: either it matures early, via progenesis, and
      produces eggs by selfing in its second intermediate host, or it waits and
      reproduces by out-crossing in its definitive host. We measured various key
      parameters of parasite fitness (i.e. hatching and multiplication rates,
      infectivity, survival) in offspring produced by both selfing and out-crossing.
      Altogether, we found no significant difference in the fitness of offspring from
      progenetic (selfing) and adult (out-crossing) parents. In addition, we found no
      evidence that either strategy (progenesis or the normal three-host cycle) is
      heritable, i.e. the strategy adopted by offspring is independent of that used by
      their parents. Although it is unclear why both reproductive strategies are
      maintained in C. parvum populations, our conclusion is that producing eggs by
      selfing has few, if any, negative effects on parasite offspring. Inbreeding
      depression is unlikely to be a factor acting on the maintenance of the normal
      three-host life cycle, and thus out-crossing, in C. parvum populations.

PMID- 19091154
TI  - The dynamics of genetically marked Ascaris suum infections in pigs.
AB  - SUMMARY: The genotypes of both host and parasite may influence the outcome of
      parasitic infections, but few attempts have been made to quantify the effect of
      parasite genotype on macroparasite infections of socio-economic importance. We
      examined variation in particular traits during the infection in pigs with the
      parasitic nematode Ascaris suum. We infected 26 pigs with mixtures of equal
      proportions of embryonated eggs from 4 single female worms each with a unique
      mtDNA haplotype--the eggs from each female worm were a mixture of siblings and
      half-siblings. Pigs were necropsied on days 14, 17 and 28 following inoculation,
      which corresponded to time-points before, during and after the main immune
      responses against the nematode. A total of approximately 11,000 worms were
      recovered at necropsy. The location in the small intestine was recorded for all
      worms and the length and mtDNA haplotype were determined for about 4200
      individual worms. There were significant differences in the distribution and
      abundance of the 4 individual haplotypes among individual pigs demonstrating
      strong interactions between parasite and host. We found significant differences
      in the abundance and position in the small intestine as well as the size of worms
      among haplotypes. We conclude that both parasite and host effects as well as the
      interplay between them play important roles in determining the characteristics
      and outcome of infection.

PMID- 19091155
TI  - Cryptopain-1, a cysteine protease of Cryptosporidium parvum, does not require the
      pro-domain for folding.
AB  - SUMMARY: Cryptosporidium parvum is an intracellular protozoan parasite that
      causes cryptosporidiosis in mammals including humans. In the current study, the
      gene encoding the cysteine protease of C. parvum (cryptopain-1) was identified
      and the biochemical properties of the recombinant enzyme were characterized.
      Cryptopain-1 shared common structural properties with cathepsin L-like papain
      family enzymes, but lacked a typical signal peptide sequence and contained a
      possible transmembrane domain near the amino terminus and a unique insert in the
      front of the mature domain. The recombinant cryptopain-1 expressed in Escherichia
      coli and refolded to the active form showed typical biochemical properties of
      cathepsin L-like enzymes. The folding determinant of cryptopain-1 was
      characterized through multiple constructs with or without different lengths of
      the pro-domain of the enzyme expressed in E. coli and assessment of their
      refolding abilities. All constructs, except one that did not contain the full
      length mature domain, successfully refolded into the active enzymes, suggesting
      that cryptopain-1 did not require the pro-domain for folding. Western blot
      analysis showed that cryptopain-1 was expressed in the sporozoites and the enzyme
      preferentially degraded proteins, including collagen and fibronectin, but not
      globular proteins. This suggested a probable role for cryptopain-1 in host cell
      invasion and/or egression by the parasite.

PMID- 19091157
TI  - Cryptic species complexes in manipulative echinostomatid trematodes: when two
      become six.
AB  - SUMMARY: Recent studies have shown that some digenean trematodes previously
      identified as single species due to the lack of distinguishing morphological
      characteristics actually consist of a number of genetically distinct cryptic
      species. We obtained mitochondrial 16S and nuclear ITS1 sequences for the redial
      stages of Acanthoparyphium sp. and Curtuteria australis collected from snails and
      whelks at various locations around Otago Peninsula, New Zealand. These two
      echinostomes are well-known host manipulators whose impact extends to the entire
      intertidal community. Using phylogenetic analyses, we found that Acanthoparyphium
      sp. is actually composed of at least 4 genetically distinct species, and that a
      cryptic species of Curtuteria occurs in addition to C. australis. Molecular data
      obtained for metacercariae dissected from cockle second intermediate hosts
      matched sequences obtained for Acanthoparyphium sp. A and C. australis rediae,
      respectively, but no other species. The various cryptic species of both
      Acanthoparyphium and Curtuteria also showed an extremely localized pattern of
      distribution: some species were either absent or very rare in Otago Harbour, but
      reached far higher prevalence in nearby sheltered inlets. This small-scale
      spatial segregation is unexpected as shorebird definitive hosts can disperse
      trematode eggs across wide geographical areas, which should result in a
      homogeneous mixing of the species on small geographical scales. Possible
      explanations for this spatial segregation of the species include sampling
      artefacts, local adaptation by first intermediate hosts, environmental
      conditions, and site fidelity of the definitive hosts.

PMID- 19091156
TI  - Detection of seminal fluid proteins in the bed bug, Cimex lectularius, using two
      dimensional gel electrophoresis and mass spectrometry.
AB  - The global increase of the human parasite, the common bed bug Cimex lectularius,
      calls for specific pest control target sites. The bed bug is also a model species
      for sexual conflict theory which suggests that seminal fluids may be highly
      diverse. The species has a highly unusual sperm biology and seminal proteins may
      have unique functions. One-dimensional PAGE gels showed 40-50% band sharing
      between C. lectularius and another cimicid species, Afrocimex constrictus.
      However, adult, sexually rested C. lectularius males were found to store 5-7
      microg of seminal protein and with only 60 microg of protein we obtained
      informative 2-D PAGE gels. These showed 79% shared protein spots between 2
      laboratory populations, and more than half of the shared protein spots were
      detected in the mated female. Further analysis using liquid chromatography
      electrospray ionization tandem mass spectrometry revealed that 26.5% of the
      proteins had matches among arthropods in databases and 14.5% matched Drosophila
      proteins. These included ubiquitous proteins but also those more closely
      associated with reproduction such as moj 29, ubiquitin, the stress-related
      elongation factor EF-1 alpha, a protein disulfide isomerase and an antioxidant,
      Peroxiredoxin 6.

PMID- 19091159
TI  - The experience of fatigue in the brain.

PMID- 19091158
TI  - Implications of modifying the duration requirement of generalized anxiety
      disorder in developed and developing countries.
AB  - BACKGROUND: A number of western studies have suggested that the 6-month duration
      requirement of generalized anxiety disorder (GAD) does not represent a critical
      threshold in terms of onset, course, or risk factors of the disorder. No study
      has examined the consequences of modifying the duration requirement across a wide
      range of correlates in both developed and developing countries. METHOD:
      Population surveys were carried out in seven developing and 10 developed
      countries using the WHO Composite International Diagnostic Interview (total
      sample=85,052). Prevalence and correlates of GAD were compared across mutually
      exclusive GAD subgroups defined by different minimum duration criteria. RESULTS:
      Lifetime prevalence estimates for GAD lasting 1 month, 3 months, 6 months and 12
      months were 7.5%, 5.2%, 4.1% and 3.0% for developed countries and 2.7%, 1.8%,
      1.5% and 1.2% for developing countries, respectively. There was little difference
      between GAD of 6 months' duration and GAD of shorter durations (1-2 months, 3-5
      months) in age of onset, symptom severity or persistence, co-morbidity or
      impairment. GAD lasting >or=12 months was the most severe, persistently
      symptomatic and impaired subgroup. CONCLUSIONS: In both developed and developing
      countries, the clinical profile of GAD is similar regardless of duration. The DSM
      IV 6-month duration criterion excludes a large number of individuals who present
      with shorter generalized anxiety episodes which may be recurrent, impairing and
      contributory to treatment-seeking. Future iterations of the DSM and ICD should
      consider modifying the 6-month duration criterion so as to better capture the
      diversity of clinically salient anxiety presentations.

PMID- 19091160
TI  - Insight correlates in child- and adolescent-onset first episodes of psychosis:
      results from the CAFEPS study.
AB  - BACKGROUND: The correlates of insight in early-onset psychosis have received
      little previous attention. METHOD: We studied clinical correlates of insight in a
      sample of 110 adolescent recent-onset psychosis patients (mean age 15.53 years;
      psychotic symptoms present for <6 months). Insight was measured with the Scale to
      Assess Unawareness of Mental Disorder (SUMD) at baseline, 6 months and 12 months
      follow-up. RESULTS: Insight improved over the early phases of the illness, in
      parallel with psychopathological improvement. Poor insight at baseline and 6
      months correlated with poor functioning at 6 and 12 months respectively.
      Schizophrenia patients had poorer insight than patients with bipolar disorder at
      6 and 12 months but not at baseline. Logistic and linear regressions were used to
      predict 12-month diagnoses and functioning based on insight measurements.
      Baseline awareness of illness was a significant predictor for diagnosis [odds
      ratio (OR) 1.4, 95% confidence interval (CI) 1.05-1.97]. Treatment compliance at
      6 months did not correlate with baseline SUMD subscores, but correlated with
      insight into having a disorder (Spearman's rho=0.21, p=0.039), its consequences
      (Spearman's rho=0.28, p=0.006) and the need for treatment (Spearman's rho=0.26,
      p=0.012) at 6 months. The 'attribution of symptoms' dimension of insight is
      poorly correlated with other insight dimensions and with other clinical
      variables. CONCLUSIONS: Poor insight correlates with symptom severity and global
      functioning but also has some trait value for schizophrenia, which is apparent
      once acute psychotic symptomatology is not prominent. A multi-dimensional
      approach to the assessment of insight is necessary, as different dimensions are
      influenced by different factors.

PMID- 19091161
TI  - A study of psychiatrists' concepts of mental illness.
AB  - BACKGROUND: There are multiple models of mental illness that inform professional
      and lay understanding. Few studies have formally investigated psychiatrists'
      attitudes. We aimed to measure how a group of trainee psychiatrists understand
      familiar mental illnesses in terms of propositions drawn from different models.
      METHOD: We used a questionnaire study of a sample of trainees from South London
      and Maudsley National Health Service (NHS) Foundation Trust designed to assess
      attitudes across eight models of mental illness (e.g. biological, psychodynamic)
      and four psychiatric disorders. Methods for analysing repeated measures and a
      principal components analysis (PCA) were used. RESULTS: No one model was endorsed
      by all respondents. Model endorsement varied with disorder. Attitudes to
      schizophrenia were expressed with the greatest conviction across models. Overall,
      the 'biological' model was the most strongly endorsed. The first three components
      of the PCA (interpreted as dimensions around which psychiatrists, as a group,
      understand mental illness) accounted for 56% of the variance. Each main component
      was classified in terms of its distinctive combination of statements from
      different models: PC1 33% biological versus non-biological; PC2 12% 'eclectic'
      (combining biological, behavioural, cognitive and spiritual models); and PC3 10%
      psychodynamic versus sociological. CONCLUSIONS: Trainee psychiatrists are most
      committed to the biological model for schizophrenia, but in general are not
      exclusively committed to any one model. As a group, they organize their attitudes
      towards mental illness in terms of a biological/non-biological contrast, an
      'eclectic' view and a psychodynamic/sociological contrast. Better understanding
      of how professional group membership influences attitudes may facilitate better
      multidisciplinary working.

PMID- 19091162
TI  - Suicide in paradise: aftermath of the Bali bombings.
AB  - BACKGROUND: The relationship between the Bali (Indonesia) bombings of October
      2002 and suicide has not previously been investigated, despite anecdotal evidence
      of the economic and psychological consequences of these attacks. METHOD: Suicide
      rates were calculated over the period 1994-2006 in three Bali regencies to
      determine whether suicide increased in the period following the first Bali
      bombings. Poisson regression and time-series models were used to assess the
      change in suicide rates by sex, age and area in the periods before and after
      October 2002. RESULTS: Suicide rates (age-adjusted) increased in males from an
      average of 2.84 (per 100 000) in the period pre-2002 to 8.10 in the period post
      2002, and for females from 1.51 to 3.68. The greatest increases in suicide in the
      post-2002 period were in the age groups 20-29 and 60 years, for both males and
      females. Tourist arrivals fell significantly after the bombings, and addition of
      tourism to models reduced relative risk estimates of suicide, suggesting that
      some of the increase may be attributable to the socio-economic effects of
      declines in tourism. CONCLUSIONS: There was an almost fourfold increase in male
      suicide risk and a threefold increase in female suicide risk in the period
      following the 2002 bombings in Bali. Trends in tourism did not account for most
      of the observed increases. Other factors such as indirect socio-economic effects
      and Balinese notions of collective guilt and anxieties relating to ritual neglect
      are important in understanding the rise in suicide in the post-2002 period.

PMID- 19091163
TI  - Exploring masculinities within men's identificatory imaginings of first-time
      fatherhood.
AB  - The changing role and practices of men as fathers is a growing subject of
      interest and debate within academic and everyday responses to contemporary
      sociocultural change. Prompted by questions about the production of identities
      and masculinities that accompanies social change, this paper is a psychosocial
      exploration of the identificatory positionings that are apparent in men's talk of
      becoming first-time fathers. Our qualitative analysis draws on a sample of 30
      heterosexual and variously skilled men aged between 18 and 40 years in Norfolk
      (UK) who were interviewed as first-time fathers just before and after the birth
      of their child. We explore aspects of men's identifications within inter
      generationally located biographies and associated social and relational contexts,
      specifically attending to ways in which men can make sense of a 'new' style of
      fatherhood, themselves and their masculinities in terms of being modern and
      traditional fathers. In adopting a psychosocial approach we are primarily
      concerned for ways in which the identificatory positions available to first-time
      fathers are conditional on a complex assemblage of dynamic mediations that are at
      once social, discursive and psychological.

PMID- 19091164
TI  - Revisiting the simple view of reading.
AB  - BACKGROUND: Reading component models such as the Simple View of Reading (SVR;
      Gough & Tunmer, 1986; Hoover & Gough, 1990) provide a concise framework for
      describing the processes and skills involved when readers comprehend texts.
      According to the Independent Review of the Teaching of Early Reading (Rose, 2006)
      strong evidence for the SVR comes from Factor Analysis of datasets on different
      measures of reading showing dissociation between decoding skills and
      comprehension. To the best of our knowledge, only two such published studies
      exist to date. Of these, only one of is in English and this explores children
      between the age of 7 and 10 years. AIMS: To explore the SVR in English-speaking
      children aged 4 and 6 using Factor Analysis. SAMPLES: 116 4-year-olds and 116 6
      year-olds in the US; 103 6-year-olds in Canada. METHODS: All children were
      administered a battery of decoding and comprehension related measures. RESULTS:
      Factor Analysis of the diverse measures undertaken independently by two research
      teams in different countries demonstrated that listening comprehension and
      decoding measures loaded as distinct factors in both samples of young English
      speaking children. CONCLUSIONS: The present findings provide important support
      for the generality and validity of the SVR framework as a model of reading.

PMID- 19091166
TI  - Attributions and affirmations for overcoming anxiety and depression.
AB  - Individuals who struggle with anxiety or depression often turn to experts for
      help in overcoming these disorders. In this study, we consult three expert
      'populations': the popular self-help literature, well-respected therapists, and
      individuals who believe that they have successfully recovered from either anxiety
      or depression for their recommendations to those who are currently anxious or
      depressed. In Part I, we content-analyse recommendations from 10 current self
      help books on anxiety and 10 on depression. In Part II, we asked 17 respected
      therapists and 18 individuals who believed that they have recovered from anxiety
      and 23 individuals who believe they have recovered from depression what they
      believe are the 'keys' for recovery. We also asked them to rate the efficacy of
      seven popular affirmations. Through content analysis and descriptive statistics,
      we summarize their collective wisdom. Among the main findings are the
      recommendations for anxious and depressed individuals to actively seek help from
      multiple people and interventions, as well as to being open to trying innovative
      self-tailored interventions. Affirmations relating to 'not being crazy' in
      relation to anxiety and that the depression will subside in time were deemed most
      helpful for recovery. Discussion focuses on practical application.

PMID- 19091165
TI  - Long-term cognitive functioning in children and adolescents who survived septic
      shock caused by Neisseria meningitidis.
AB  - AIMS: To assess long-term cognitive functioning and its predictors, in children
      and adolescents who survived meningococcal septic shock (MSS) 4 to 16 years ago.
      METHODS: The Wechsler Intelligence Scale for Children-third edition was used to
      measure intellectual functioning and neuropsychological tests were used to
      measure attention, verbal memory, visual-motor integration, and executive skills.
      RESULTS: Overall, results of the total MSS sample (N=77) as to neuropsychological
      functioning were similar to those of normative reference groups. On social and
      practical reasoning and visual-motor integration, however, MSS children obtained
      poorer outcomes compared to normative data. Two children had mental retardation
      (estimated IQ<70) due to the MSS. The percentage of children with mental
      retardation or borderline intellectual functioning (15%) was similar to that in
      the general population (16%). Eighteen children (23%) had a z score<-2,
      indicating unusual poor functioning, on one or more domains of neuropsychological
      functioning (selective attention, sustained attention, and executive
      functioning). Compared to normative data, significantly more children had
      received special education services in the past. Older age at time of follow-up
      was the most important significant predictor of poorer long-term cognitive
      functioning. CONCLUSION: Overall, long-term outcomes as to cognitive functioning
      of the total MSS sample were similar to those of normative reference groups, but
      MSS children showed long-term impairments on social and practical reasoning,
      visual-motor integration, attention, and executive functioning. Older age at time
      of follow-up was a significant predictor.

PMID- 19091167
TI  - Surgical procedures and non-surgical devices for the management of non-apnoeic
      snoring: a systematic review of clinical effects and associated treatment costs.
AB  - OBJECTIVES: To review the evidence on the clinical effects and associated
      treatment costs of surgical procedures and non-surgical devices for the
      management of non-apnoeic snoring. DATA SOURCES: Major electronic databases were
      searched for relevant studies published between 1980 and 2007. All treatment
      costs were estimated based on data from NHS reference costs, device manufacturers
      and clinical opinion. REVIEW METHODS: Studies were screened, data extracted and
      quality assessed according to standard methods. Results were broadly grouped
      according to the intervention and comparator when applicable, and further
      subgrouped according to the specific intervention type and study design. Results
      were combined using a narrative synthesis with relevant quantitative results
      tabulated. Differences between studies assessing the same intervention were
      explored narratively by examining differences in the intervention, study duration
      and study quality. RESULTS: The systematic review included 27 studies (three
      randomised controlled trials, two controlled clinical trials and 22 pre-post
      studies) reported in 30 publications assessing uvulopalatopharyngoplasty (UP3)
      versus laser-assisted uvulopalatoplasty (LAUP), UP3 alone, LAUP alone, palatal
      stiffening techniques (Pillar implants and injection snoreplasty), radiofrequency
      ablation (RFA) of the soft palate or tongue base, continuous positive airway
      pressure (CPAP) devices and mandibular advancement splints (MAS). Studies were
      generally of a low methodological quality with small sample sizes. A total of
      1191 patients was included. Both UP3 and LAUP reduced the number of snores per
      hour and produced a modest reduction in snoring loudness. UP3 was effective in
      reducing a number of subjectively reported snoring indices, but results on
      objective measures were equivocal. Limited evidence indicates that subjectively
      assessed snoring is improved after LAUP; no objective measures were assessed. RFA
      was associated with a reduction in partner-assessed snoring intensity, though
      evidence for an objective reduction in snoring sound levels was mixed. Pillar
      implants were moderately effective at reducing partner-rated snoring intensity,
      but had no effect on objective snoring indices. Use of CPAP reduced the number of
      snores per hour; no subjective measures were evaluated. Use of MAS improved
      objective snoring outcomes, including the maximal snoring sound volume, the mean
      snoring sound volume and the percentage of time spent in loud snoring; no
      subjective measures were evaluated. The cost for UP3 ranges from approximately
      1230 pounds to approximately 1550 pounds. For LAUP the cost varies from 790
      pounds to 2070 pounds depending on the number of stages of the procedure. The
      treatment costs associated with the use of Pillar implants range from 1110 pounds
      to 1160 pounds. The approximate annual treatment costs associated with the use of
      a CPAP machine and MAS are 220 pounds and 130 pounds respectively. CONCLUSIONS:
      This study highlighted the paucity and poor quality of the evidence available on
      the effects of both surgical procedures and non-surgical devices for the
      management of primary snoring. Any conclusions to be drawn from the results are
      therefore somewhat tentative. There was no procedure that was clearly the least
      cost option. Further research should focus on standardising methods of measuring
      outcomes and reporting, undertaking active controlled trials, and investigating
      the longer-term effects of treatments.

PMID- 19091168
TI  - Is combination therapy with aspirin and extended-release dipyridamole more
      effective than clopidogrel for preventing recurrent stroke?

PMID- 19091169
TI  - The role of cholesterol and statins in stroke.
AB  - Flawed observational studies find weak associations between high cholesterol and
      ischemic stroke, and low cholesterol and hemorrhagic stroke. Low-density
      lipoprotein cholesterol, high-density lipoprotein cholesterol, and triglycerides
      each appear to have individual effects on stroke risk and type. Statins decrease
      the risk of cerebral infarction in patients with coronary disease, diabetes,
      hypertension, and hypercholesterolemia. They also significantly decrease the risk
      of ischemic stroke in patients with recent cerebrovascular disease, while
      potentially increasing the risk of intracerebral hemorrhage. Lower achieved
      cholesterol values are associated with greater reductions in stroke risk. Besides
      their cholesterol-lowering properties, statins are also pleiotropic agents with
      various neuroprotective mechanisms. Neurologic disability and infarct size are
      decreased in patients administered statins during stroke. Mortality and
      neurologic deterioration are higher in patients with statin cessation during
      acute ischemic stroke. Cholesterol is a modifiable risk factor for stroke, and
      statins are excellent agents for prophylaxis and acute therapy.

PMID- 19091170
TI  - Inflammatory markers and stroke.
AB  - Basic and animal research implicate inflammatory mechanisms in the pathogenesis
      and progression of atherosclerosis, plaque rupture, thrombosis, and stroke.
      Inflammatory biomarkers, particularly high-sensitivity C-reactive protein and
      lipoprotein-associated phospholipase A2, have been identified as potential
      predictors of stroke risk and prognosis. Infections may also precipitate stroke.
      Medications, especially hydroxymethylglutaryl coenzyme A reductase inhibitors
      (statins), reduce inflammatory marker levels independently of lipid effects, and
      the ability of statins to reduce coronary events and stroke correlates with their
      effect on inflammatory biomarkers. Vaccination against influenza may also reduce
      stroke risk. Determining whether reduction of biomarkers reduces risk of
      recurrent stroke, however, requires further study before inflammatory markers
      become a routine part of the evaluation of stroke patients.

PMID- 19091171
TI  - Carotid plaque compared with intima-media thickness as a predictor of coronary
      and cerebrovascular disease.
AB  - Atherosclerosis is the underlying cause of most myocardial infarction (MI) and
      ischemic strokes. B-mode ultrasound of carotid arteries provides measures of
      intima-media thickness (IMT) and plaques, both widely used as surrogate measures
      of cardiovascular disease. Although IMT and plaques are highly intercorrelated,
      IMT's role as a marker of atherosclerosis has been questioned, especially when
      measurements include the common carotid artery (CCA) only. Plaque and intima
      media thickening may reflect different biological aspects of atherogenesis with
      distinctive relations to clinical vascular disease. Plaque measured in the
      carotid bulb or internal carotid artery is stronger related to hyperlipidemia and
      smoking and is a stronger predictor for MI, whereas CCA-IMT is stronger related
      to hypertension and ischemic stroke. Echolucent plaque morphology (ie, lipid-rich
      plaques) seems to increase the risk for MI and stroke. New evidence suggests that
      total plaque area is the most strongly predictive of cardiovascular risk of the
      ultrasound phenotypes.

PMID- 19091172
TI  - Aortic arch plaque in stroke.
AB  - Patients with severe aortic arch plaque are at high risk for stroke. This article
      addresses the complex nature of the association between aortic arch plaque and
      stroke. The aortic arch plaque poses a diagnostic and therapeutic challenge to
      the clinician. The different imaging modalities currently available for
      evaluating aortic plaque are discussed. Therapy to prevent emboli from aortic
      plaque is not yet established. Retrospective data in patients with severe aortic
      plaque support using oral anticoagulation and statins to prevent stroke.
      Iatrogenic embolization can occur as a result of aortic manipulation during
      invasive vascular procedures or cardiovascular surgery. The risks and benefits of
      these procedures must be carefully weighed, and alternate approaches should be
      considered for patients with severe aortic arch plaque. Assessing aortic arch
      plaque combined with a specific prevention strategy may reduce the risk of its
      feared complication, stroke.

PMID- 19091174
TI  - The prognostic importance of unrecognized myocardial scar in diabetic patients as
      identified by cardiac magnetic resonance.

PMID- 19091173
TI  - Management of hyperglycemia during acute stroke.
AB  - Long-term complications of hyperglycemia are well known, but short-term
      complications are not. Because hyperglycemia and hypoglycemia can be corrected
      relatively rapidly, it seems important to determine if such interventions during
      acute illnesses improve patient outcomes. In most animal stroke studies, animals
      with hyperglycemia before or during brain ischemia have worse outcomes than those
      with normoglycemia. In humans, hyperglycemia during acute stroke has been
      associated with worse clinical outcomes than normoglycemia, but it remains to be
      established if rapid correction of the hyperglycemia will improve patient
      outcomes. Intravenous insulin infusion protocols are the only currently
      established methods to effectively lower and control hyperglycemia during acute
      illness. Recent pilot clinical trials demonstrate feasibility and safety of such
      interventions. One randomized efficacy trial has been reported and additional
      trials are needed. In the meantime, an intermediate approach to managing acute
      stroke hyperglycemia with subcutaneous insulin seems reasonable.

PMID- 19091175
TI  - Coronary CT angiography: clinical utility and prognosis.
AB  - In recent years, technologic advances in multidetector CT have permitted
      acquisition of virtually motion-free images of the heart and coronary arteries
      with high spatial resolution. Paralleling these developments has been a growing
      clinical interest in the application of coronary CT angiography (CCTA) as for
      noninvasive evaluation of individuals with suspected coronary artery disease.
      Nevertheless, many questions remain unanswered regarding CCTA use in specific
      clinical scenarios. This article focuses on contemporary data that relates to the
      diagnostic performance and potential for risk stratification of the current
      generation CCTA. Furthermore, we propose a suggested algorithm for its use in
      daily clinical practice.

PMID- 19091176
TI  - Cardiac magnetic resonance stress testing: results and prognosis.
AB  - Cardiac stress magnetic resonance (MR) testing has been developed and optimized
      in the past decade, reaching a high diagnostic performance. Its efficacy,
      together with its excellent safety profile and increasing availability, make
      cardiac stress MR testing one of the diagnostic modalities of choice for
      detecting ischemia. A noticeable series of studies validated the diagnosis of
      ischemia with MR compared with coronary angiography and other noninvasive
      diagnostic techniques and invasive hemodynamic measurements. In addition, first
      data on the usefulness of cardiac stress MR testing in assessing prognosis has
      become available. This article reviews the available literature about diagnostic
      performance of cardiac stress MR testing and its results in the prognostication
      of cardiac patients.

PMID- 19091177
TI  - Cardiovascular magnetic resonance of cardiomyopathies.
AB  - Cardiomyopathies are a heterogeneous group of diseases of the myocardium
      associated with architectural abnormalities and mechanical dysfunction. Recent
      advances in our understanding of the genetics, pathophysiology, and natural
      history of these conditions has resulted in better diagnosis and management,
      leading to improvements in mortality. Major developments in imaging techniques,
      in particular contrast-enhanced MRI, now permit in vivo tissue characterization
      of the myocardium. Through defining disease severity, etiology, and to some
      extent in risk stratification, routine cardiovascular magnetic resonance
      evaluation of this group of patients provides essential information required in
      everyday clinical practice.

PMID- 19091179
TI  - Lessons from a respiratory illness outbreak in an aged-care facility.
AB  - This report outlines practical lessons learnt from an influenza-like outbreak in
      an aged-care facility in NSW, which affected 26 residents, resulted in 14
      hospital admissions and was associated with six deaths. No common causative agent
      was identified. Key recommendations include: encouraging aged-care facilities to
      establish mechanisms that improve the early identification of outbreaks and
      timely implementation of outbreak control strategies; identifying strategies to
      inform general practitioners of outbreaks if they have patients residing in aged
      care facilities; and improving the vaccination coverage of the aged-care
      workforce.

PMID- 19091178
TI  - Atherosclerotic plaque imaging by carotid MRI.
AB  - Carotid MRI (CMRI) is a valuable technique to examine the state of carotid
      atherosclerotic plaque in vivo. This article examines CMRI's current and future
      directions. These include technical requirements for implementing CMRI, as well
      as applications of CMRI, such as visualizing lesion types, plaque components,
      dynamic contrast imaging, comparison of stenosis and other measures of plaque
      burden, and ongoing knowledge gained from serial studies. Also, future directions
      of CMRI and how CMRI techniques can be transitioned into clinical practice are
      addressed.

PMID- 19091180
TI  - Evidence of pertussis clusters in three aged-care facilities in the former
      Macquarie Area Health Service, NSW.
AB  - During a limited outbreak of pertussis in an area health service in NSW, three
      clusters occurred in aged-care facilities--the first reported outbreaks of
      pertussis in Australian nursing homes. The attack rates across the three clusters
      were 16.7% for staff and 15.7% for residents. Our investigation revealed that
      older adults are not immune to pertussis. We suggest methods for controlling a
      pertussis outbreak in an aged-care facility.

PMID- 19091181
TI  - Hospital and non-hospital costs for fall-related injury in community-dwelling
      older people.
AB  - OBJECTIVES: This study determined the cost of fall-related health care in a
      cohort of community-dwelling people. METHODS: 578 people aged 75 years and over
      were monitored for falls and related health-care costs for one year. RESULTS: The
      mean cost per injurious fall was $1600 (year 2000 dollars). Hospital costs
      accounted for 67% of the total cost, even though only 4% of injurious falls
      required hospital admission. The cost of non-hospital health care was also
      substantial. CONCLUSION: This study highlights the economic burden of falls and
      the importance of injury prevention strategies.

PMID- 19091182
TI  - Incidence of falls and fall-related outcomes among people in aged-care facilities
      in the Lower Hunter region, NSW.
AB  - This article describes the rate of falls and adverse outcomes following falls,
      such as fracture, hospitalisation and death, among residents of 88 aged-care
      facilities in the Lower Hunter region of NSW from July to December 2005. A high
      rate of falls was observed with a crude incidence of 171 falls per 1000 beds per
      month. Around 40% of the falls resulting in hospitalisation were for fractured
      neck of femur. Estimated 3-month survival following fractured neck of femur was
      low, with a rate ratio of around 1 : 3. The data indicate an urgent need for
      falls injury prevention in aged-care facilities.

PMID- 19091183
TI  - Environmental health risk assessment of nickel contamination of drinking water in
      a country town in NSW.
AB  - OBJECTIVES: To assess the health risks associated with consumption of drinking
      water with elevated nickel concentration in a NSW country town named Sampleton.
      METHODS: We used enHealth Guidelines (2002) as our risk assessment tool.
      Laboratory test results for nickel in water samples were compared with the
      Australian Drinking Water Guidelines 2004 and the World Health Organization's
      (WHO) Guidelines for Drinking Water Quality 2005. RESULTS: The mean nickel
      concentration in the drinking water samples tested over a 4-year period (2002
      2005) was 0.03 mg/L (95% CI: 0.02-0.04). The average daily consumption of two
      litres of water by a 70-kg adult provided 0.06 mg (0.03 mg x 2) of nickel, which
      was only 7% of the lowest observed adverse effect level (LOAEL) based on
      experiments on nickel-sensitive people in a fasting state. CONCLUSIONS: The mean
      nickel concentration in drinking water appears to have no health risks for the
      inhabitants of Sampleton.

PMID- 19091184
TI  - Managing environmental lead in Broken Hill: a public health success.
AB  - OBJECTIVES: To describe locality-specific changes in blood lead levels of 1-4
      year-old children in Broken Hill, NSW between 1991 and 2007. METHODS: Annual age
      sex standardised mean blood lead levels, blood lead screening clinic attendance
      rates and lead-dust levels for five lead-risk zones were calculated from
      routinely collected data. RESULTS: Blood lead levels were similar in all
      localities in 2002, 2003, 2005 and 2006, after having been consistently higher in
      localities with highest environmental lead since 1991. CONCLUSIONS: Combining
      health promotion with a targeted clean-up has reduced the effect of locality on
      blood lead levels. Results are consistent with reduced contamination due to
      effective soil stabilisation and storm-water control.

PMID- 19091185
TI  - Addressing decreasing blood lead screening rates in young children in Broken
      Hill, NSW.
AB  - This paper outlines the findings of a review commissioned in response to concerns
      about declining attendance of young children for blood lead screening in Broken
      Hill, NSW. A review of the literature and feedback from the local community
      revealed that reasons for reduced screening attendance elsewhere can be applied
      here, but that any proposed response should take account of local conditions.

PMID- 19091186
TI  - [Screening for dementia among immigrants and refugees].

PMID- 19091187
TI  - [Dementia in elderly Turkish immigrants].
AB  - INTRODUCTION: The health condition in a population of elderly Turkish immigrants
      is investigated with special focus on dementia conditions. The possibility to use
      the screening test Mini Mental State Examination (MMSE) in relation to the
      investigated population is evaluated as well as their future need for a nursing
      home. MATERIAL AND METHODS: With the help of an interpreter, the Turkish
      population of elderly (> 60 years old) in the municipality of Ishoj was
      interviewed about educational-, working- and health conditions. In addition to
      MMSE and semi-structured interviews, the ICD-10 criteria were used in diagnosing
      dementia conditions. RESULTS: We found an increased frequency of dementia
      conditions (13,3%) compared to the expected prevalence of 7% in the Danish
      population. Furthermore, we found an increased frequency of diabetes type-2. The
      use of MMSE as a guideline instrument of screening was shown to be applicable
      only with modifications to persons who were illiterates and without any
      education, and to those 1st-generation immigrants who were to a limited degree
      integrated as citizens CONCLUSION: The increased incidence of dementia conditions
      and diabetes type-2 shows the need for a more assertive approach.

PMID- 19091188
TI  - [Adrenalectomy in Denmark 2002-2006].
AB  - INTRODUCTION: Laparoscopic adrenalectomy is replacing open adrenalectomy. The
      advantages are reduced mortality and morbidity, and shorter postoperative
      hospitalisation. The organization and short-term outcomes of adrenalectomy in
      Denmark are largely unknown. MATERIAL AND METHODS: Extraction, review, and
      analysis of data from the National Patient Register and discharge notes from 2002
      2006. RESULTS: A total of 297 adrenalectomies, of which 161 were laparoscopic,
      were identified. Discharge notes were reviewed in 221 of these cases (2002-2005).
      All except three were performed in a university hospital setting. The
      laparoscopic to open conversion rate was 7.6%, mortality 1%, and complication
      rates for open/laparoscopic adrenalectomy 25%/16%. The mean postoperative
      hospital stays on surgical/urological wards were 6.0/2.9 days for open and
      laparoscopic procedures, respectively. CONCLUSION: In Denmark, the share of
      adrenalectomies performed laparoscopically is growing, currently reaching about
      65%. Laparoscopic adrenalectomies are only performed at departments with a high
      frequency of laparoscopic surgery and specialized endocrinological and
      anaesthesiological support. For educational and research purposes, adrenalectomy
      should be performed at an even smaller number of departments. Postoperative
      hospital stay and mortality are at par with internationally reported levels, but
      the conversion rate of laparoscopic adrenalectomies should be reduced.

PMID- 19091189
TI  - [Diabetic retinopathy during pregnancy].
AB  - INTRODUCTION: The aim was to evaluate the prevalence and progression of diabetic
      retinopathy during pregnancy in women with type 1 or type 2 diabetes. MATERIAL
      AND METHODS: Dilated fundal photography was performed at approximately 10 and 28
      gestational weeks in 58 and 18 women with type 1 and type 2 diabetes,
      respectively. Retinopathy was classified as five stages +/- macular oedema.
      Progression was defined as deterioration corresponding to at least one stage
      between the two examinations. Clinical parameters were obtained from the medical
      records. RESULTS: Diabetic retinopathy was found in 36 (62%) women with type 1
      and three (17%) with type 2 diabetes at the first examination. In 26 (34%)
      retinopathy progressed; four women developed proliferations, three macular oedema
      and three reduction of visual acuity >/=0.2 on Snellen's chart in at least one
      eye. HbA1c in early pregnancy was the only significant predictor of progression
      (odds ratio = 1.75, 95% confidence interval = 1.09-2.82). Progression of
      retinopathy also tended to be associated with type 1 diabetes and long diabetes
      duration. CONCLUSION: The risk of progression of diabetic retinopathy during
      pregnancy was considerable, especially among women with high HbA1c values in
      early pregnancy. A few women developed proliferations, macular oedema and
      reduction of visual acuity. Development of sight-threatening alterations during
      pregnancy remains a clinical problem.

PMID- 19091190
TI  - [Are systematic consultation invitations and spirometry in general practice
      useful in the prevention of COPD among smokers?].
AB  - INTRODUCTION: There is a need for valid tools to help people stop smoking. The
      aim of this study was to investigate whether or not systematic invitation of
      patients for a consultation and spirometry and the subsequent follow-up including
      the identified COPD patients in general practice is expedient in prevention of
      COPD among smokers. MATERIAL AND METHODS: The entire population of 40-50-year-old
      patients listed with ten general practitioners in Southern Jutland received a
      questionnaire and a letter in which smokers were invited to attend a consultation
      with their GP to have their lung function measured. Patients diagnosed with
      chronic obstructive pulmonary disease (COPD) were offered renewed testing and
      guidance to quit smoking. RESULTS: A total of 2299 questionnaires were sent out,
      299 smokers responded (11.3% of the total number of patients), and 185 of the
      respondents (71.4%) attended an initial consultation. Twelve patients were
      diagnosed with COPD and thus met the criteria for invitation to renewed testing,
      but only five accepted the invitation. None of the patients who accepted renewed
      testing changed their smoking habits. CONCLUSION: Systematic invitations for
      consultation and spirometry in general practice as COPD prevention has proven to
      be difficult. Various models should be assessed before large scale interventions
      are implemented.

PMID- 19091191
TI  - [Deaths among drug addicts in Eastern Denmark 2005].
AB  - INTRODUCTION: The purpose of this study was to investigate deaths among drug
      addicts in Eastern Denmark in 2005, partly fatal poisonings, partly deaths where
      the cause of death not was a poisoning and to compare the results with those
      reported in studies from 1991, 1997 and 2002. MATERIAL AND METHODS: All deaths
      among drug addicts investigated at the Institute of Forensic Medicine in
      Copenhagen. RESULTS: The number of deaths among drug addicts was 160 of which 64%
      were due to fatal poisoning. The number of drug addict deaths has remained almost
      constant in the period 1991-2005, but in 2002 and 2005 a decrease of about 10%
      was seen in the fraction of fatal poisonings. As in 2002, a decrease in the
      fraction of heroin/morphine poisonings was seen, and an increase in the fraction
      of methadone poisonings with a proportion of heroin/morphine poisonings of 17%
      and a proportion of methadone poisonings of 39%. As in the previous studies, the
      most commonly detected drugs were methadone, heroin/morphine, benzodiazepines and
      cannabis and, as in 2002, methadone was more frequently detected than
      heroin/morphine. In the non-poisoning deaths, the most frequent manner of death
      was natural death (44%). In 12% the manner of the death was suicide, in 14% death
      was accidental, in 4% homicide was the manner of death and in 26% the manner of
      death was undetermined. CONCLUSION: The increase in the number of fatal
      poisonings with methadone and the decrease in the number of fatal poisonings with
      heroin/morphine seen in the 2002 study continued in 2005. The poly-drug use had
      increased in 2005 with more drugs detected in each case than before.

PMID- 19091192
TI  - [Bariatric surgery in Denmark--are we on the right way?].
AB  - INTRODUCTION: In 2005 the National Board of Health (NBH) published guidelines on
      bariatric surgery in Denmark. The aim of the present study was to shed light on
      the national bariatric effort in relation to these guidelines. MATERIAL AND
      METHODS: The analysis is based on extraction of the following data from the
      National Patient Registry in the period from 2005 through 2007: annual number of
      operations, type of operation, laparoscopic versus open procedure. Furthermore,
      the centres were compared. RESULTS: A total of 2,098 bariatric procedures were
      performed in the years 2005 to 2007. Apart from a single operation, all
      operations were performed at departments selected by the NBH. During the period
      an increase of approximately 400% in the number of operations was observed, and
      the rise was largest at the private clinics, which performed approx. 60% of the
      operations in 2007. Not all public departments fulfilled the recommendation from
      the NBH of a minimum of 100 annual operations. The proportion of banding
      procedures performed at private clinics was significantly lower than the
      proportion performed at public hospitals. Significantly more open operations were
      performed at private clinics, a tendency which was attributable to the activities
      of one of the private clinics. CONCLUSION: The frequency with which bariatric
      surgery is performed follows a strongly increasing trend and the procedures are
      only performed at the public departments selected by the National Board of Health
      and at the private centres that have entered into an agreement with Danish
      Regions. Since the operative access and selection of procedures varies between
      departments we conclude that research should be a firm requirement for all
      centres, and that research efforts should comprise cooperation concerning the
      database recommended by the NBH.

PMID- 19091193
TI  - [Tumor necrosis factor-alpha antibody for maintenance of remission in Crohn
      disease. A survey of a Cochrane review].

PMID- 19091194
TI  - [Treatment of fistulating pouchitis with tumour necrosis factor-alpha-inhibitor
      (infliximab)].
AB  - The surgical first choice treatment for patients with ulcerative colitis (UC)
      involves total proctocolectomy with ileal pouch-anal anastomosis (IPAA).
      Postoperative development of pouch-related fistula is a rare complication, but it
      is associated with significant morbidity, a high recurrence rate and is a major
      cause of pouch failure. We report the use of infliximab, a monoclonal antibody to
      tumour necrosis factor-alpha, in three patients who developed pouch-related
      fistula after undergoing IPAA surgery for UC.

PMID- 19091195
TI  - [Measurement of myocardial perfusion using magnetic resonance].
AB  - Cardiac magnetic resonance imaging (MRI) has evolved rapidly. Recent developments
      have made non-invasive quantitative myocardial perfusion measurements possible.
      MRI is particularly attractive due to its high spatial resolution and because it
      does not involve ionising radiation. This paper reviews myocardial perfusion
      imaging with MR contrast agents: methods, validation and experiences from
      clinical studies. Unresolved issues still restrict the use of these techniques to
      research although clinical applications are within reach.

PMID- 19091196
TI  - [Osteoid osteoma in the hip of 12-year-old girl].
AB  - Osteoid osteoma is a benign skeletal tumour most commonly located in the cortex
      of long bones and easily diagnosed with distinct symptoms and radiographic
      appearance. The less common peri-articular location presents a diagnostic
      difficulty due to its non-specific symptoms and the absence of radiological
      findings in the early state. This often leads to a delay in the final diagnosis
      and treatment. A case review of a young girl diagnosed with periarticular osteoid
      osteoma of the acetabulum is reported.

PMID- 19091197
TI  - [Osmotic demyelination syndrome in Addison crisis and severe hyponatremia].
AB  - Acute adrenal insufficiency is a life threatening disease with dehydration,
      hypotension, cerebral dysfunction and gastrointestinal symptoms accompanied by
      low plasma sodium and high plasma potassium. Osmotic demyelination syndrome (ODS)
      can occur rarely following correction of plasma sodium. We describe a case with
      extremely low plasma sodium and subsequent development of ODS. Correction which
      is too slow may lead to cerebral oedema, brain stem herniation and low sodium
      encephalopathy. Correction which is too fast may cause ODS. The dilemma is
      accentuated by concomitant Addison crisis.

PMID- 19091198
TI  - [Methadone: Medical treatment or dealing?].
AB  - A woman with schizophrenia in methadone treatment was admitted for treatment of
      psychotic symptoms and cocaine addiction. Her prescribed medication was a 400 mg
      daily dose of methadone. It became evident during her hospitalisation that she
      was only taking a small part of the medication herself and she sold the rest of
      the methadone to finance her addiction of cocaine. To address this kind of misuse
      of prescribed medication, this paper examines the importance of following
      guidelines put forward by the NBH (National Board of Health).

PMID- 19091199
TI  - [Six-month effectiveness and tolerability of pioglitazone in combination with
      sulfonylureas or metformin for the treatment of type 2 diabetes mellitus].
AB  - BACKGROUND AND OBJECTIVE: Pioglitazone has been reported to improve common
      cardiovascular risk factors in addition to glycemic control in patients with type
      2 diabetes mellitus (T2DM). The changes in cardiovascular risk profile were
      evaluated comparatively in large cohorts either treated or not with pioglitazone
      containing combinations in the current clinical setting within Spain. PATIENTS
      AND METHOD: A nationwide prospective, controlled, observational cohort clinical
      study was performed in 2294 patients with T2DM who started, at the criterion of
      the treating physician, oral antihyperglycemic treatment with either pioglitazone
      plus a sulfonylurea (Pio+SU; n=851), pioglitazone plus metformin (Pio+Met; n=723)
      or a sulfonylurea plus metformin (SU+Met; n=720) due to inadequate control with
      previous therapy. Serum cholesterol, blood glucose, hemoglobin A1C, blood
      pressure and certain anthropometric parameters were measured at baseline and
      after 6 months of treatment. RESULTS: Serum high density lipoprotein-cholesterol
      increased in average (mg/dl) 2.08 with Pio+SU, 2.06 with Pio+Met and 0.67 with
      SU+Met; while triglycerides decreased (mg/dl) 26.6, 30.6 and 17.6 in the same
      cohorts. Inter-group differences were significant (p<0.001 in both parameters).
      Total cholesterol decreased significantly more with SU+Met than in the
      pioglitazone cohorts. Mean fasting plasma glucose and hemoglobin A1C reductions
      were significantly greater in the pioglitazone cohorts than in the SU+Met cohort:
      27.74, 28.94 and 23.46 mg/dl (p=0.012); and 0.80, 0.87 and 0.71% (p=0.016) with
      Pio+SU, Pio+Met and SU+Met, respectively. Slight, but significant variations of
      body weight were also registered in the Pio+SU (+1.4 kg) and SU+Met (-0.7 kg)
      groups. CONCLUSIONS: Treatment with pioglitazone was associated with significant
      improvements of lipid and glycemic parameters that are linked to insulin
      resistance and cardiovascular risk in patients with T2DM in their routine
      clinical care. The non-randomised allocation of patients to treatments, inherent
      to its observational design, is an important limitation of the present study.

PMID- 19091200
TI  - [Early prediction of psychosocial intervention needs in pneumology patients after
      nurses' evaluation].
AB  - BACKGROUND AND OBJECTIVE: This study was aimed to verify whether it is possible
      to detect at hospital admission, by means of INTERMED, pneumonology patients at
      risk of "complexity" and of specialized psychosocial intervention. PATIENTS AND
      METHOD: With the Spanish version of INTERMED (for detection of risk for
      complexity of care) 144 patients were interviewed at admission by a standardized
      nurse. At discharge, patients were reassessed blindly with standardized Spanish
      versions of instruments including the Hospital Anxiety and Depression Scale
      (HADS). Somatic illness variables were independently documented, and severity was
      assessed by means of the Cumulative Illness Rating Scale. All variables were
      operationalized including complex (IM+; INTERMED>20) and non-complex patients (IM
      ), and probable need of psychosocial treatment/intervention. Statistical analysis
      included multivariate logistic regression. RESULTS: A complex course was
      documented in 9.6% of patients, and 28.8% had complex discharge. Significantly
      higher proportions of severe anxiety and/or depression were documented in IM+
      cases (12.1%) when compared to IM- cases (0.9%), and the need of psychosocial
      treatment/intervention was also significantly more frequent among the former
      (24.2% versus 6.3% respectively). Furthermore, in the multivariate analysis and
      controlling for medical and sociodemographic confounders INTERMED was
      significantly associated with the variable need of psychosocial intervention.
      CONCLUSIONS: In support of the clinical utility of the INTERMED method (Spanish
      version), this is the first report in the international literature documenting
      that standardized nurses are able to detect at admission those medical patients
      who will eventually need specialized psychosocial intervention.

PMID- 19091201
TI  - [Diagnostic usefulness of N-terminal brain natriuretic peptide in patients
      admitted to a cardiology service].
AB  - BACKGROUND AND OBJECTIVE: The N-terminal brain natriuretic peptide (NT-proBNP) is
      a new tool for the diagnosis of patients with evidence of heart failure (HF). The
      diagnosis of HF is improbable in patients with a level of NT-proBNP<300 pg/ml.
      Our objective is to determine the validity of the cut-off points proposed by
      literature (inclusion/exclusion) regarding the age for NT-proBNP in patients
      admitted to our service. PATIENTS AND METHOD: We gathered consecutively the data
      of 76 patients admitted to our service with the diagnosis of HF (n=37) and with
      other diseases (n=39), taking a sample of plasma to determine NT-proBNP. We
      studied the sensitivity, specificity and predictive values of this test, as well
      as the relation between the levels of that marker and the clinical and
      echocardiographic variables. RESULTS: The ventricular diameter was larger and the
      ejection fraction was lower in patients with HF. Sensitivity for the diagnosis of
      exclusion reached a value of 97% and the negative predictive value was 94%.
      CONCLUSIONS: The cut-off point proposed for exclusion (300 pg/ml) shows high
      sensitivity and negative predictive value in the diagnosis of HF in patients
      admitted to our service.

PMID- 19091202
TI  - [NT-proBNP for the diagnosis of acute heart failure: where are we now?].

PMID- 19091203
TI  - [Alstrom syndrome: clinical and genetic features, and a diagnostic guide to
      foresee complications].
AB  - BACKGROUND AND OBJECTIVE: Alstrom syndrome is a progressive autosomal recessive
      genetic disorder affecting multiple organ systems. It may be detected at birth or
      in early childhood. Clinically, patients with Alstrom syndrome develop cone-rod
      dystrophy leading to eventual blindness, sensorineural deafness, and normal
      intelligence. Patients develop obesity, endocrine disturbances such as type 2
      diabetes mellitus, dilated cardiomyopathy and progressive renal and hepatic
      failure. Alstrom syndrome is caused by specific mutations in the ALMS1 gene,
      located at chromosome 2p13. PATIENTS AND METHOD: A case of a 23 year old patient
      with Alstrom syndrome, with a previous diagnosis of Laurence-Moon-Bardet-Biedl is
      described. RESULTS: The subsequent molecular study revealed a mutation on the
      ALMS1 gene, confirming the diagnosis of Alstrom syndrome. CONCLUSIONS: The low
      frequency, the progressive multi-systemic disturbances, and the similarities with
      other well-known syndromes may difficult the diagnosis of Alstrom syndrome. Thus,
      without a careful examination, it may be misdiagnosed and it would not be
      possible to perform any anticipatory therapeutic approach, with dramatic
      consequences for the patients and their families. Moreover, as these patients
      must have a multidisciplinary approach, they may not receive the adequate
      treatment on time. therefore, it seems important to publish this case in our
      country, among with the clinical and molecular characteristics of this syndrome,
      and to spread a diagnostic and anticipatory guidance for its early detection.

PMID- 19091204
TI  - [Stem cells treatment for patients with heart diseases].

PMID- 19091205
TI  - [Effect of caffeine on athletic performance].

PMID- 19091206
TI  - [Sleep apnea and insomnia: a frequent association].

PMID- 19091207
TI  - [Long-term follow-up of three cases of haemolytic anemia associated with
      ulcerative colitis].

PMID- 19091208
TI  - [Acalculous cholecystitis: first manifestation of polyarteritis nodosa in a
      patient with primary Sjogren].

PMID- 19091209
TI  - [Intestinal manifestation of type 1 Gaucher disease despite enzyme replacement
      therapy].

PMID- 19091210
TI  - [Antiphospholipid antibodies, antiphospholipid syndrome and suprarenal
      haematoma].

PMID- 19091211
TI  - [Miliary tuberculosis].

PMID- 19091212
TI  - [Who won the debate? Reflections on the future of dermatopathology].

PMID- 19091213
TI  - [Psoriasis and HIV infection].
AB  - Dermatologists face diagnostic and therapeutic difficulties when psoriasis
      coexists with human immunodeficiency virus (HIV) infection. This article will
      review some of the aspects of this coexistence from the epidemiologic,
      pathogenic, histopathologic, clinical, and prognostic point of view. The main
      skin diseases that should be included in the differential diagnosis are
      described. Also analyzed are the different therapeutic options in these patients
      according to the degree of immunodeficiency. Possibilities include antiretroviral
      treatment, topical treatment, retinoids, and classic immunosuppressants. The
      review will also cover current literature on the use of new biologic therapies in
      patients with HIV infection. Finally, we will discuss the risk of drug
      interactions during psoriasis treatment in these patients, who receive multiple
      pharmacologic therapies.

PMID- 19091215
TI  - [Strategies for getting published in high-impact dermatology journals].
AB  - For a manuscript to be published in prestigious dermatology journals, its content
      must be of sufficient scientific merit and properly presented in terms of
      structure, format, and style. Even when this is the case, targeting the wrong
      journal may cause substantial delay in publication. When choosing a journal,
      authors often give too much priority to English language journals, overestimate
      the actual importance of the study, give too much weight to the impact factor or
      reputation of the journal, and fail to examine carefully the instructions for
      authors. However, one of the main mistakes is to fail to assess whether the
      information in a manuscript is in line with the editorial policy or the interests
      of the readers of a given journal. An honest and objective assessment of the true
      scientific value of the study and the relevance of the conclusions is the best
      criterion for selecting the dermatological journal of choice, regardless of
      prestige, impact factor, inclusion in databases, or other considerations.

PMID- 19091214
TI  - [Pityriasis versicolor and the yeasts of genus Malassezia].
AB  - Although pityriasis versicolor is the only human disease for which Malassezia
      yeasts have been fully established as pathogens, it is still not clear which
      species are implicated. Most studies carried out in recent years support our
      hypothesis - proposed in 1999 - that Malassezia globosa is the predominant
      species in pityriasis versicolor lesions, at least in temperate climates.
      Confirmation of this hypothesis could help us understand the conditions, as yet
      unclear, that induce transformation of this yeast from the saprophytic form
      present in healthy skin to the parasitic form, characterized by the formation of
      pseudomycelium, and could also guide therapy. In addition, isolation of another
      species, Malassezia furfur, which seems to be predominant in the tropics, raises
      the possibility of a second etiologic agent confined to certain areas, as occurs
      with some other human mycoses.

PMID- 19091216
TI  - [Retrospective, descriptive, observational study of treatment of multiple actinic
      keratoses with topical methyl aminolevulinate and red light: results in clinical
      practice and correlation with fluorescence imaging].
AB  - BACKGROUND: Actinic keratosis (AK) is one of the most common skin diseases seen
      in clinical practice. In the last 5 years, several studies assessing the efficacy
      of photodynamic therapy in the treatment of multiple AKs have been published.
      OBJECTIVE: We aimed to assess the clinical outcomes of photodynamic therapy in
      patients with multiple AKs and the correlation of those outcomes with
      fluorescence imaging. MATERIAL AND METHODS: In this retrospective, descriptive,
      observational study of 57 patients treated in our hospital with photodynamic
      therapy for multiple AKs, we recorded age, sex, and lesion site (face, scalp, and
      dorsum of the hands). All patients were treated in the same way: methyl
      aminolevulinic acid (Metvix) was applied for 3 hours and the skin then irradiated
      with red light at 630 nm, 37 J/cm(2), for 7.5 minutes (Aktilite). The response,
      remission duration, tolerance, number of sessions, and fluorescence images were
      recorded by site. The chi(2) test was used to assess between-site differences and
      the correlation between fluorescence imaging and clinical response. RESULTS: The
      greatest improvements were obtained for facial lesions; these required fewer
      sessions and remission lasted longer than lesions at other sites. The treatment
      was best tolerated on the dorsum of the hands. The fluorescence area and the
      reduction in intensity on applying treatment were found to be strongly and
      significantly correlated with the extent of clinical response. CONCLUSIONS:
      Overall, the outcomes of treatment of multiple AKs with photodynamic therapy are
      better for the face than for the scalp and dorsum of the hands. Fluorescence
      imaging may be an effective tool for predicting response to treatment.

PMID- 19091218
TI  - [Sensitization to acrylates caused by artificial acrylic nails: review of 15
      cases].
AB  - BACKGROUND: Allergic contact dermatitis due to acrylates present in the workplace
      is a disease frequently reported among dentists, printers, and fiberglass
      workers. Recently, the number of cases of contact allergic dermatitis among
      beauticians specialized in sculpting artificial nails has increased. OBJECTIVE:
      Our objective was to study the clinical characteristics and allergens implicated
      in allergic contact dermatitis due to acrylates in beauticians and users of
      sculpted nails. MATERIAL AND METHODS: This was an observational, retrospective
      study of patients diagnosed with allergic contact dermatitis due to acrylates
      used in sculpting artificial nails over the last 26 years in the Hospital General
      Universitario, Valencia, Spain. RESULTS: In total, 15 patients were diagnosed: 14
      beauticians and 1 client. Most cases were diagnosed in the past 2 years. All were
      women, their mean age was 32.2 years, and 26.7 % had a personal or family history
      of atopy. The sensitization time varied between 1 month and 15 years. The most
      frequently affected areas were the fleshy parts of the fingers and hands. Three
      patients - 2 beauticians and 1 client - presented allergic asthma due to
      acrylates. All patients underwent patch testing with a standard battery of
      allergens and a battery of acrylates. The most frequent allergens were ethylene
      glycol dimethacrylate (13/15, 86.7 %), hydroxyethyl methacrylate (13/15, 86.7 %),
      triethylene glycol dimethacrylate (7/15, 46.7 %), 2-hydroxypropyl methacrylate
      (5/15, 33.3 %), and methyl methacrylate (5/15, 33.3 %). CONCLUSIONS: Acrylate
      monomers used for sculpting artificial nails are important sensitizers for
      contact and occupational dermatitis. The most important consideration is primary
      and secondary prevention.

PMID- 19091219
TI  - [An economic analysis of presurgical teledermatology in patients with nonmelanoma
      skin cancer].
AB  - INTRODUCTION: In patients with nonmelanoma skin cancer, store-and-forward
      teledermatology allows satisfactory diagnosis and surgical planning, thus
      shortening waiting lists and reducing travel requirements for patients in special
      situations. OBJECTIVE: The aim of this study was to undertake an economic
      analysis of presurgical teledermatology, comparing it with a conventional health
      care approach. MATERIAL AND METHODS: The cost and cost-effectiveness of
      presurgical teledermatology were analyzed from a societal perspective in the
      setting of a public hospital with a corporate intranet. The mean delay in surgery
      was used to measure effectiveness. Over a 12-month period, teledermatology was
      used in 134 patients with nonmelanoma skin cancer. The unit cost of each
      intervention (teledermatology and conventional health care approach), the cost
      ratio between the most and least expensive alternative, and the incremental cost
      effectiveness ratio were calculated. We distinguished between 2 groups of
      patients: those with and those without physical impediments for travel. RESULTS:
      The unit cost of the patients in whom teledermatology was used was euro 156.40
      compared to euro 278.42 per patient in the conventional system; the conventional
      system was therefore 1.78 times more expensive than presurgical teledermatology.
      Teledermatology was more cost-effective, with an incremental cost-effectiveness
      ratio of euro 3.10 per patient and per day of delay avoided in patients without
      impediments for travel and euro 4.87 in those with impediments for travel.
      CONCLUSION: Teledermatology used for remote presurgical planning and preparation
      in patients with nonmelanoma skin cancer is more cost-effective than the
      conventional referral system in a health setting with a communication network
      available.

PMID- 19091220
TI  - [Chronic graft-versus-host disease presenting as bullous lesions].
AB  - Graft-vs-host disease is still the leading cause of morbidity and mortality in
      patients undergoing bone marrow transplantation. It is important to start
      treatment early to reduce the severity and consequences of this complication.
      Cutaneous lesions are often the presenting compliant of graft-vs-host disease and
      presage visceral involvement. We present the case of a 45-year-old woman with
      multiple myeloma who underwent autologous and subsequently allogeneic bone marrow
      transplantation with hematopoietic precursors. She developed bullous lesions with
      fluid elimination on the abdomen and legs. Biopsy findings were compatible with
      graft-vs-host disease and immunosuppressive therapy was increased. She
      subsequently presented oral lichenoid lesions and sicca syndrome. The bullous
      lesions progressed to painful ulcers that healed leaving highly sclerodermatous
      skin with substantial hyperpigmentation. Bullous lesions are a rare form of
      presentation of chronic graft-vs-host disease. In such cases, the diagnosis may
      not be suspected initially, particularly when the lesions are isolated and
      internal organs are not involved.

PMID- 19091221
TI  - [Patient with generalized guttate morphea and lichen sclerosus et atrophicus].
AB  - Generalized guttate morphea is a very uncommon clinical entity, and few reports
      are available in the literature. We report the case of a 7-year-old boy who first
      attended our clinic in 1990 with guttate morphea on the trunk and upper limbs.
      These lesions were associated with plaque morphea on his right foot. Twelve years
      later, lesions with a different appearance to the previous ones were observed in
      the right pectoral region. Clinically and histopathologically, they resembled
      lichen sclerosus et atrophicus. Given that morphea and lichen sclerosus et
      atrophicus share certain clinical and pathologic characteristics, some authors
      believe that these entities may be related or even different presentations of the
      same disease. The most noteworthy aspect of our case is the type of morphea, as
      we were unable to find equivalent examples in the literature.

PMID- 19091222
TI  - [Papules on the dorsum of the fingers].

PMID- 19091223
TI  - [Painful nodule on the sole of the foot].

PMID- 19091224
TI  - [Plaque of tinea circinata: infection from a cow].

PMID- 19091226
TI  - [Cutaneous presentation of plasmablastic lymphoma in a patient with HIV
      Infection].

PMID- 19091227
TI  - [Patient with "lobster claw" hands and feet: ectrodactyly-ectodermal dysplasia
      cleft syndrome].

PMID- 19091228
TI  - [Multiple unilateral facial angiofibromas: description of a new case].

PMID- 19091229
TI  - [Flexural comedones].

PMID- 19091230
TI  - [Pale orange perifollicular halo as a dermatoscopic sign in scurvy].

PMID- 19091231
TI  - [Single reticulohistiocytoma mimicking a keratoacanthoma].

PMID- 19091232
TI  - [A new cover for the new year].

PMID- 19091233
TI  - [Tuberculosis and solidarity].

PMID- 19091234
TI  - [Anti-factor Xa activity of enoxaparin for thromboprophylaxis in nonsurgical
      patients is dependent on body mass].
AB  - OBJECTIVE: Thromboprophylaxis with a fixed dose of low-molecular-weight heparin
      is recommended for hospitalized acutely ill medical patients. The purpose of this
      study was to assess whether the anti-factor Xa (anti-Xa) activity of enoxaparin
      prescribed for venous thromboembolism prophylaxis depends on body mass index
      (BMI) in patients hospitalized for an acute respiratory disease. PATIENTS AND
      METHODS: All patients admitted to the respiratory medicine department (January
      December 2006) for an acute respiratory disease, and for whom pharmacologic
      thromboprophylaxis was indicated, were included in the study. Anti-Xa activity
      was measured 4 hours after administration of enoxaparin on the third day of
      hospitalization. The primary outcome was anti-Xa activity in relation to BMI.
      RESULTS: One hundred twelve patients were enrolled. Mean anti-Xa activity
      decreased with each BMI quartile (0.28, 0.23, 0.15, and 0.13 U/mL for quartiles
      1, 2, 3, and 4, respectively). In the multivariate analysis, BMI was the only
      predictor of inadequate anti-Xa activity (odds ratio, 1.14; 95% confidence
      interval, 10.5-1.24; P< .002) after adjustment for age, sex, and serum creatinine
      levels. Two episodes of symptomatic proximal deep vein thrombosis were diagnosed
      in the month after hospitalization; both occurred in patients who had inadequate
      anti-Xa activity. CONCLUSIONS: Anti-Xa activity is dependent on BMI in
      hospitalized acute medical patients receiving enoxaparin for thromboprophylaxis.

PMID- 19091236
TI  - [Diaphragmatic response is influenced by previous muscle activity].
AB  - OBJECTIVE: Previous muscle activity can alter muscle contractility and lead to
      strength underestimation or overestimation in functional measurements. The
      objective of this study was to evaluate changes in the maximum pressure produced
      by the diaphragm after different series of spontaneous near-to-maximal isometric
      contractions. METHODS: Duplicate studies were performed on 6 dogs with a mean
      (SD) weight of 26 (7) kg. The supramaximal response of the diaphragm was achieved
      by simultaneous supramaximal stimulation of both phrenic nerves, both under basal
      conditions and after series of 5, 10, and 20 spontaneous inspiratory efforts
      against the occluded airway, performed before and after spinal anesthesia (which
      eliminates the ventilatory contribution of the intercostal muscles). The response
      was measured using the twitch gastric pressure (Pga) and twitch esophageal
      pressure (Pes) and by muscle shortening (sonomicrometry). RESULTS: The short
      series of 5 inspiratory efforts and, in particular, the medium series of 10
      efforts produced potentiation of the contractile response, with a rise in the Pga
      from 3.2 (0.4) cm H(2)O to 3.7 (0.3) cm H(2)O, and from 3.5 (0.3) cm H(2)O to 3.9
      (0.3) cm H(2)O, respectively (P=.05 in both cases). The potentiation was somewhat
      greater after subarachnoid anesthesia (an increase in the Pga of 21% after the
      medium series of 10 efforts with anesthesia vs 11% without anesthesia). However,
      the long series of 20 efforts produced a fall in the response, with a decrease in
      the Pga from 3.2 (0.4) cm H(2)O to 2.5 (0.3) cm H(2)O (P< .05), probably due to
      fatigue overcoming the effect of potentiation. CONCLUSIONS: Previous effort
      affects the contractile capacity of the diaphragm and it is difficult to predict
      the predominance of fatigue or potentiation in the response. This factor must be
      taken into account when determining the maximum respiratory pressures in daily
      clinical practice.

PMID- 19091235
TI  - [Cost-effectiveness analysis of automatic titration of continuous positive airway
      pressure at home in 1 night versus 2 nights].
AB  - OBJECTIVE: To assess the cost-effectiveness of automatic continuous positive
      airway pressure (CPAP) titration at home on 1 night or 2 consecutive nights in
      patients with the sleep apnea-hypopnea syndrome (SAHS). PATIENTS AND METHODS: A
      home titration study was performed using automatic CPAP for 2 consecutive nights
      on 100 patients with SAHS and an indication for CPAP. The number of successful
      studies and the costs of the first night and both nights were analyzed. The
      pressure requirements on each night and the agreement between the pressures
      selected visually by 2 different observers were compared. RESULTS: CPAP titration
      was successful in 85% and 80% of patients on the first night and second night,
      respectively, and in 88% of patients after both nights. No significant
      differences between the 2 nights were found for the following parameters: 95th
      percentile pressure (mean [SD], 10.2 [1.8] cm H(2)O and 10.2 [1.6] cm H(2)O on
      the first and second nights, respectively), mean pressure (7.8 [1.7] cm H(2)O and
      7.7 [1.7] cm H(2)O), or the pressure selected visually (9.4 [1.5] cm H(2)O and
      9.4 [1.4] cm H(2)O). Interobserver agreement on the pressure selected was good:
      the k statistics were 0.956 for the first night and 0.91 for the second night.
      The 1-night study cost euro232.63 and the 2-night study cost euro227.93.
      CONCLUSIONS: Automatic CPAP titration at home for 1 night enables a substantially
      greater number of patients to be studied at a similar cost than is possible when
      titration is accomplished in 2 consecutive nights.

PMID- 19091237
TI  - [Nontuberculous mycobacterial infection in patients with cystic fibrosis: a
      multicenter prevalence study].
AB  - OBJECTIVE: To determine the prevalence of nontuberculous mycobacterial infection
      in patients with cystic fibrosis. PATIENTS AND METHODS: We performed a
      prospective study in which patients with cystic fibrosis were followed for 2
      years; the patients were recruited from specialized units and were all over 6
      years old. Sputum samples collected every 6 months were stained with auramine
      rhodamine and cultures were prepared with a liquid and a solid medium. When
      stains or cultures were positive for nontuberculous mycobacteria, 1 or 2
      additional sputum samples were obtained from the patients, who were monitored
      closely to assess the need for specific treatment. We assessed the following
      clinical variables: age, sex, presence of pancreatic insufficiency, use of
      aerosol antibiotic therapy, and long-term azithromycin and inhaled or oral
      corticosteroid therapies. RESULTS: A total of 220 patients (119 women) with a
      mean age of 22.62 years (range, 6-74 years) were enrolled; of these 23.6% were
      receiving azithromycin. We prepared 1303 sputum samples for mycobacterial growth
      (range per patient, 4-68 samples); 65 samples from a total of 17 patients (7.72%)
      were positive: 17 by auramine-rhodamine staining and 48 by culture. Eighty-eight
      culture samples were contaminated and Mycobacterium tuberculosis was not isolated
      in any of the cases. The mycobacteria isolated were M avium complex (n=10), M
      abscessus (n=6), and M fortuitum (n=1). Two or more positive cultures were
      obtained in 9 patients, 5 of whom experienced clinical deterioration and were
      prescribed specific treatment. No significant differences in clinical variables
      were found between patients with nontuberculous mycobacteria and those without.
      CONCLUSIONS: The prevalence of nontuberculous mycobacterial infection in patients
      with cystic fibrosis was not very high (7.72%), perhaps because azithromycin
      interfered with the growth of these bacteria. Patients with repeat isolations of
      mycobacteria should be monitored closely.

PMID- 19091238
TI  - [Differences in clinical and polysomnographic variables between male and female
      patients with sleep apnea-hypopnea syndrome].
AB  - OBJECTIVE: The aim of this study was to compare the clinical, anthropometric, and
      polysomnographic characteristics of a broad group of patients with sleep apnea
      hypopnea syndrome according to sex. PATIENTS AND METHODS: The study, conducted in
      6 Spanish university hospitals, included consecutive patients attended from 2003
      through 2005 with an apnea-hypopnea index greater than 5. Groups were formed
      according to sex and then stratified into age subgroups of younger (< or = 45
      years) and older patients (> 45 years) for further comparison. RESULTS: The study
      included 2464 men and 424 women. Women were older (mean [SD] age, 56 [12] years
      vs 51 [12] years), weighed more (body mass index, 31 [6] kg/m(2) vs 30 [5]
      kg/m2), and had a larger hip circumference (119 [15] cm vs 111 [12] cm) and
      smaller neck circumference (38 [3] cm vs 42 [9] cm) than men (P< .001 in all
      cases). The degree of daytime sleepiness (Epworth scale) and the apnea-hypopnea
      index were similar in both groups, although women had a longer sleep latency (23
      [28] minutes vs 27 [32] minutes; P< .004) and a higher mean oxygen saturation
      (92% [4%] vs 91% [5%]) and minimum oxygen saturation (78% [11%] vs 75% [12%]; P<
      .0001) than men. On stratification by age, only weight differences between men
      and women were observed in the younger group whereas the older group also showed
      differences in oxygen saturation during sleep. CONCLUSIONS: Women with sleep
      apnea-hypopnea are more overweight than men and tend to seek medical attention at
      an older age. The clinical and polysomnographic variables were generally similar
      for men and womenthe only differences were that sleep latency was longer and
      hypoxemia during sleep was more accentuated in women.

PMID- 19091239
TI  - [Experience with imatinib to treat pulmonary arterial hypertension].
AB  - Despite advances in the treatment of patients with pulmonary arterial
      hypertension (PAH), survival has not improved greatly (is still very affected).
      Imatinib, an antagonist of platelet-derived growth factor with antiproliferative
      activity, has been effective in experimental models and clinically in several
      published reports. We report the results of imatinib therapy in 4 patients with
      PAH (functional class IV) who were refractory to treatment with drug combinations
      for this condition. The final outcome was favorable in only 1 of the 4 cases. In
      this case, the patient was in functional class III and his hemodynamic parameters
      had improved significantly within 5 months after starting therapy. However, the
      patient died as a result of severe toxic hepatitis in which imatinib may have
      played a role. The present report adds to the few already in the literature (4
      cases) and suggests that care should continue to be shown when using imatinib to
      treat PAH.

PMID- 19091240
TI  - [A medical alternative for the treatment of localized hyperhidrosis].

PMID- 19091241
TI  - [Severe Laryngotracheal Involvement in a Case of Rhinoscleroma Due to Klebsiella
      pneumoniae Subspecies ozaenae].

PMID- 19091242
TI  - [Adult celiac disease and intraepithelial lymphocytes. New options for
      diagnosis?].
AB  - BACKGROUND: Permanent changes have been found in intraepithelial lymphocyte (IEL)
      subsets in patients with celiac disease. OBJECTIVE: The main aim of this study
      was to demonstrate the utility of determining CD3()/CD7(+) and T cell receptor
      (TCR) gamma-delta IEL subsets by flow cytometry as a diagnostic marker of adult
      celiac disease. PATIENTS AND METHODS: We performed a prospective study in a
      sample of 128 adult patients (70 with celiac disease and 58 controls). In all
      patients, distal duodenal biopsy was performed and IEL subsets were determined by
      flow cytometry. RESULTS: Patients with celiac disease showed an increase in gamma
      delta IEL subsets and a decrease in CD3(-)/CD7(+) IEL subsets in comparison with
      the control group, independently of diet. CONCLUSIONS: The results indicate that
      IEL subset determination by flow cytometry could be useful to confirm diagnosis
      of celiac disease. IEL subsets should be investigated in diseases other than
      celiac disease, as well as in patients with potential or latent celiac disease.

PMID- 19091243
TI  - [Prognostic value of a spontaneous bacterial peritonitis episode in cirrhotic
      patients in clinical practice].
AB  - OBJECTIVES: To assess survival and predictive factors of mortality after an
      episode of spontaneous bacterial peritonitis (SBP) in cirrhotic patients and to
      analyze the diagnostic and therapeutic measures used. METHODS: We retrospectively
      reviewed the medical records of 158 consecutive episodes of SBP treated between
      January 2003 and December 2005. Survival was studied by Kaplan-Meier curves,
      compared by the log-rank test. Independent predictive factors of mortality were
      obtained by a Cox regression model, while independent predictive factors of in
      hospital mortality were obtained by logistic regression analysis. RESULTS: A
      total of 80.4% of the SBP episodes occurred in men and the mean age was 61.23 +/-
      12.49 years. The most frequent etiology of cirrhosis was viral (51.3%), followed
      by alcoholic (39.9%). The distribution of Child-Pugh classification was 5.7% (A),
      63.3% (B) and 31% (C). Overall 3-year survival in the sample was 43.3%. Four
      variables were identified as independent predictive factors of in-hospital and 3
      month mortality: renal impairment, hepatic encephalopathy, diagnosis of
      hepatocellular carcinoma (HCC) and mean arterial pressure (MAP) < 75 mmHg. At the
      end of the monitoring period, the results of the analysis were as follows:
      diagnosis of HCC, MAP < 75 mmHg, and age > 65 years. Microbiological detection
      was achieved in 21% of the episodes. The most frequent microorganisms detected
      were Escherichia coli in ascitic fluid and Staphylococcus aureus in blood
      cultures. CONCLUSIONS: SBP has a poor short- and long-term prognosis in cirrhotic
      patients. Independent predictive factors of short-term survival are renal
      impairment, hepatic encephalopathy, MAP < 75 mmHg, and the presence of HCC.

PMID- 19091244
TI  - [Patient satisfaction in gastrointestinal endoscopy: results of a multicenter
      study].
AB  - BACKGROUND AND AIM: The aim of this study was to determine the main quality
      problems perceived by patients in gastrointestinal endoscopy through a
      satisfaction survey. PATIENTS AND METHODS: A total of 321 patients from five
      gastrointestinal endoscopy units were included. Telephone interviews using a
      previously validated questionnaire on several aspects related to the procedure
      were carried out. Pareto analyses were performed to pinpoint the most common
      aspects among the vital few causes at each medical center. Based on the
      questionnaire, the satisfaction indicators were calculated for each center: the
      overall satisfaction score (the sum of the responses to the eight questions) and
      the rate of perceived problems (number of questions with a negative response
      divided by the number of questions asked). RESULTS: The most frequent aspects
      among the vital few were waiting time for an appointment and discomfort during
      the examination, since both factors were included in the vital few in four of the
      five medical centers. Significant differences were found among centers in the
      overall satisfaction score (questionnaire score) (p < 0.001) and for the rate of
      perceived problems (p < 0.001). CONCLUSION: According to the patients, the most
      problematic aspects were waiting time until the day of the appointment and
      discomfort during the examination. Perceived quality differed among the
      participating centers.

PMID- 19091245
TI  - [Endoscopic mucosal resection of Abrikosoff's tumor of the esophagus].
AB  - Abrikosoff's tumor (AT), or granular cell tumor (GCT), is relatively rare in the
      gastrointestinal tract, where the most common site is the esophagus. This tumor
      is usually found incidentally when an upper gastrointestinal endoscopy is carried
      out for another reason. Endoscopically, GCT appears as a small, yellow and
      submucosal lesion covered by normal mucosa. Endoscopic ultrasonography shows a
      homogeneous hypoechoic lesion with well defined margins. The definitive diagnosis
      is histological. The origin of GCT is neurogenic and the tumor is composed of
      eosinophilic granular cytoplasm and PAS-positive cells, which show the S-100
      protein on immunohistochemistry. Although GCT is usually clinically and
      histologically benign, some malignant cases have been reported. Consensus is
      lacking on the treatment and follow-up of this tumor. Currently, endoscopic
      mucosal resection is a safe and effective technique to treat submucosal
      esophageal lesions, allowing subsequent histologic analysis. We present three
      patients with esophageal CGT, who were definitively treated with endoscopic
      mucosal resection.

PMID- 19091246
TI  - [Fungal liver abscesses in a patient with primary sclerosing cholangitis and
      Crohn's disease].
AB  - Liver abscesses are a relatively infrequent complication of inflammatory bowel
      disease. These abscesses are usually multiple and of polymicrobial origin. The
      development of primary sclerosing cholangitis in inflammatory bowel disease,
      although provoking alterations in biliary morphology and a higher incidence of
      infections, does not predispose patients to the development of liver abscesses.
      We describe a new case of primary sclerosing cholangitis and Crohn's disease with
      multiple fungal liver abscesses caused by Candida albicans. The patient had
      developed a duodenal-biliary fistula. Antibiotic therapy produced clinical
      response and surgery was performed to repair the fistula.

PMID- 19091247
TI  - [New perspectives in predicting response to chemotherapy in colorectal cancer].
AB  - In the last few years, major advances have been produced in knowledge of the
      pathogenesis of colorectal cancer, which have led to the development of new drugs
      for the treatment of this disease. Likewise, molecular markers have been
      identified that are useful in prognosis. However, decisions on adjuvant therapy
      in colorectal cancer continue to be based exclusively on histological stage.
      Distinct markers that can be detected in tumoral tissue may be useful in
      predicting response to antineoplastic drugs. The present article reviews the
      possible clinical utility of these markers and their role in decision-making in
      the treatment of patients with colorectal cancer.

PMID- 19091248
TI  - [Pelvic floor disorders].
AB  - Fecal and urinary incontinence are frequently associated, together with pelvic
      organ prolapse. The most important risk factors for pelvic floor disorders are
      vaginal delivery and chronic constipation. Irrespective of the symptom prompting
      the patient to seek medical attention and the specialist consulted, symptoms in
      other compartments must be investigated because patients rarely report them
      spontaneously. Patients with pelvic floor disorders should be evaluated by a
      multidisciplinary group of specialists. Complete evaluation includes urodynamics,
      anal manometry, endoanal ultrasonography and neurophysiologic study of the pelvic
      floor and is recommended in most patients, given that pelvic floor disorders have
      a complex and multifactorial pathophysiology and that all anatomic and functional
      abnormalities must be detected to provide the most appropriate treatment.
      Conservative treatment resolves or improves the problem in a large proportion of
      patients with mild-to-moderate symptoms. Surgery should be indicated in selected
      patients with careful evaluation to identify preoperatively all anatomical and
      functional defects that can be surgically corrected. The identification of risk
      factors and better knowledge of the prevalence and pathophysiology of this health
      problem will allow preventive strategies to be established and improve
      therapeutic outcomes.

PMID- 19091249
TI  - [Treatment of hepatitis C virus infection: current status and perspectives].
AB  - Current treatment of patients with chronic hepatitis C consists of pegylated
      interferon and ribavirin. The application of viral kinetics is currently allowing
      treatment to be optimized by varying the length of treatment to 24 weeks for
      genotypes 2 and 3 and 48 weeks for the remaining genotypes. Thus, patients with
      genotype 1, with a low viral load, and rapid virological response (RVR) obtain a
      high RVS with 24 weeks' treatment. In contrast, slow responders may benefit from
      72 weeks' treatment. Patients with genotypes 2 and 3 can also benefit from
      regimens designed according to viral kinetics. Higher doses and more prolonged
      periods have been tested in non-responders to current treatment, although for
      many, the only option is to wait for a new generation of drugs. Maintenance
      therapy with low-dose interferon to prevent cirrhosis and hepatocarcinoma is
      currently being evaluated.

PMID- 19091250
TI  - [Adrenal insufficiency in cirrhosis].
AB  - Cortisol is a pluripotent hormone that is vital in the host adaptation to stress.
      It is essential to maintain the normal vascular tone, endothelial integrity and
      vascular permeability. Consequently, the failure of an appropriate adrenal
      response in the setting of critical illness, alteration known as relative adrenal
      insufficiency, may have important clinical consequences. The diagnosis of this
      entity is not possible on clinical grounds and relies on the measurement of
      plasma cortisol levels prior and after adrenal stimulation with synthetic
      corticotrophin. Several studies performed in the general population have shown
      that relative adrenal insufficiency contributes to vascular hyporesponsiveness in
      septic shock and increases mortality. However, contradictory data exist regarding
      the effects of hydrocortisone administration in these patients. Moreover, recent
      studies indicate that relative adrenal insufficiency is very frequent in patients
      with advanced cirrhosis and septic shock and in fulminant hepatic failure. This
      chapter summarizes the main aspects of the physiopathology, diagnosis and
      treatment of this entity in patients with acute or chronic liver disease.

PMID- 19091251
TI  - [Gastrointestinal oncology. Is surgery required when the histology of an
      endoscopically resected polyp reveals the presence of adenocarcinoma foci?].

PMID- 19091252
TI  - [Functional gastrointestinal disorders. What type of laxative should be used in
      patients with chronic constipation? What are the indications for irritant
      laxatives?].

PMID- 19091253
TI  - [Pancreas and biliary tree. In patients with acute pancreatitis, what monitoring
      measures and treatment are essential in the first 72 h after onset?].

PMID- 19091254
TI  - [Inflammatory bowel disease. Should bone densitometry always be performed when
      corticosteroids are prescribed in a flare of inflammatory bowel disease?].

PMID- 19091255
TI  - [Gastrointestinal endoscopy. Is decompressive endoscopy indicated as the first
      line measure in patients with acute colonic pseudoobstruction, also known as
      Ogilvie syndrome?].

PMID- 19091256
TI  - [Acid-related diseases. In anticoagulated patients with active gastrointestinal
      bleeding due to peptic ulcer and an INR of 6, should plasma be transfused,
      parenteral vitamin K be administered, or both measures?].

PMID- 19091257
TI  - [Colonic-cutaneous fistula after placement of a percutaneous gastrostomy tube].

PMID- 19091258
TI  - [Perforation of hollow viscera associated with cocaine use].

PMID- 19091260
TI  - [A 25-year-old man with pancreatic tumor, double vision and bone lesions].

PMID- 19091259
TI  - [Viral clearance in wild-type hepatitis B virus after treatment with pegylated
      interferon alpha-2a].

PMID- 19091261
TI  - [Infliximab as rescue therapy after cyclosporin in an acute ulcerative colitis
      flare].

PMID- 19091262
TI  - Hyperventilation and finger exercise increase venous-arterial Pco2 and pH
      differences.
AB  - INTRODUCTION: Since the invention of the pulse oximeter, physicians often or even
      routinely perform venous blood gas analysis (VBGA). However, it has not been
      generally agreed that the application of VBGA is practically meaningful in
      routine clinical situations such as in an ED. METHODS: We measured venous
      arterial Pco(2) difference ((v-a)Pco(2)) and arterial-venous pH difference ((a
      v)pH), and analyzed the physiological factors that affect these differences in
      healthy volunteers and hyperventilation patients. RESULTS: In healthy volunteers,
      both (v-a)Pco(2) and (a-v)pH increased during finger exercise or hyperventilation
      in an intensity-dependent manner. Doppler echography indicated that increases in
      (v-a)Pco(2) and (a-v)pH during hyperventilation are induced by reduction of
      peripheral blood flow. Approximately 40% of patients with untreated respiratory
      alkalosis were found to be incorrectly diagnosed if based only on VBGA.
      CONCLUSIONS: It must be noted that VBGA may lead to overestimation of acidosis
      and to underestimation of respiratory alkalosis when extremities muscles are
      active or patients are hyperventilating. Physicians should keep these limitations
      in mind when conducting VBGA.

PMID- 19091263
TI  - Oxygen inhalation using an oxygen concentrator in a low-pressure environment
      outside of a hospital.
AB  - Supplementation with oxygen is fundamental in rescue and emergency medicine.
      However, transportation of oxygen cylinders or a rigid hyperbaric chamber
      requires large work forces. Also, oxygen in a cylinder may be completely consumed
      during a rescue action. The oxygen concentrators, which enrich the oxygen
      percentage of ambient air, may free rescuers from carrying heavy oxygen
      cylinders. In the present study, 2 types of oxygen concentrators were tested in a
      mountain hut located at an altitude of 3776 m. Oxygen concentration of the
      generated gas was 28.6% +/- 0.8% with the first machine, which was powered by an
      internal battery. Arterial oxygen saturation of the volunteers inhaling through
      the machine increased from the original 79% +/- 6% to 82% +/- 6%. When the
      machine was used with a semi-closed circuit, the value increased further to 90%
      +/- 3%. The second concentrator, which was powered by an external electric
      generator, outputted 90% +/- 2% oxygen. Arterial oxygen saturation of the
      volunteers increased to 95% +/- 1%. It is concluded that both types of oxygen
      concentrators were efficient at high altitude.

PMID- 19091264
TI  - Adverse events associated with ketamine for procedural sedation in adults.
AB  - STUDY OBJECTIVES: Ketamine is widely used as a procedural sedation agent in
      pediatrics, where its safety and efficacy are supported by numerous studies.
      Emergency physicians use ketamine infrequently in adults, as it is believed to
      have a more significant side effect profile in this population. However, adult
      data on ketamine use in the emergency medicine literature are sparse. Our
      objective was to determine ketamine's adverse effect profile in adults when used
      for procedural sedation. METHODS: We performed a literature review based on
      adverse effect research methodology recommendations. PubMed, EMBASE, TOXNET, and
      a variety of specialized databases were queried without regard to publication
      date or language. Experts were contacted to locate additional data. Inclusion
      criteria included adult study; ketamine used to facilitate the performance of
      painful procedures; dose of at least 1 mg/kg intravenous or at least 2 mg/kg
      intramuscular; original data and adverse events reported; spontaneously breathing
      patient, and no continuous cotherapies. Studies that met inclusion criteria were
      abstracted onto structured forms and their results qualitatively summarized.
      RESULTS: Of the 5512 unique citations that were evaluated, 87 met criteria for
      inclusion. Most studies were performed in the 1970s and published in the
      anesthesia literature. Contexts, end points, and methodological quality varied
      widely across studies. Ketamine reliably produces conditions that facilitate the
      performance of painful procedures. Pharyngeal reflexes are generally preserved
      and cardiovascular tone stimulated, including a rise in blood pressure and
      myocardial oxygen demand. Laryngospasm and airway obstruction are reported, and
      though ketamine is a respiratory stimulant, a brief period of apnea around the
      time of injection is common. Reports of significant cardiorespiratory adverse
      events are rare, despite ketamine's frequent use in austere, poorly monitored
      settings. Dysphoric emergence phenomena occur in 10% to 20% of cases; sedating
      medications are effective in preventing and managing these reactions. CONCLUSION:
      When ketamine is used for procedural sedation in adults, emergence phenomena
      occur in 10% to 20% of patients. Although providers must be prepared to recognize
      and manage airway obstruction, cardiorespiratory adverse events are rare and
      typically do not affect outcomes.

PMID- 19091265
TI  - Pain treatment and relief among patients with primary headache subtypes in the
      ED.
AB  - OBJECTIVE: The aim of this study is to determine if emergency physicians treat
      headache subtypes differently and if this difference affects pain relief.
      METHODS: This was a prospective observational, institutional review board
      approved study of adults undergoing treatment for a primary headache. Before the
      treatment and 60 minutes after, patients completed a 100-mm Visual Analog Scale
      (VAS) describing their pain. Patients also completed a headache diagnosis
      worksheet that differentiated headache type based on International Headache
      Society criteria. Treatments were recorded. Data were analyzed using descriptive
      statistics, 95% confidence intervals, analysis of variance, and chi(2) tests as
      appropriate. RESULTS: A total of 184 patients were enrolled: 83 (45.1%) with
      migraine, 61 (33.2%) with migrainous, and 40 (21.7%) with tension-type headaches.
      There was no difference in the presenting VAS score or treatments of the 3
      headache subtypes. The migraine group was most likely to receive any pain
      medication (78.31%), and the tension group the least likely to receive any pain
      medication (62.50%). A 50% decrease in VAS was achieved by only 32.5% of the
      patients. Sumatriptan, followed by droperidol, provided the greatest decrease in
      VAS scores. Oral and parenteral narcotics provided equivalent pain relief, with
      nonsteroidal anti-inflammatory drugs (NSAIDs) providing the least pain relief.
      CONCLUSION: There was no difference in the treatments used or pain relief
      achieved between migraine, migrainous, and tension-type headaches. The
      differentiation of primary headache subtypes does not appear to be important to
      their treatment in the acute setting of the emergency department.

PMID- 19091266
TI  - Meteorological parameters and seasonal variations in pulmonary thromboembolism.
AB  - BACKGROUND AND OBJECTIVES: In recent years, circannual variations in incidence
      and mortality for venous thromboembolic disease have been demonstrated, with a
      peak in winter. However, several investigators have observed no seasonal
      variation in these diseases. The aim of our study was to investigate whether a
      seasonal variation, in terms of atmospheric pressure, humidity, and temperature,
      exists for pulmonary thromboembolism. METHOD: We retrospectively included 206
      patients with a diagnosis of pulmonary embolism (PE) between 1 June 2001 and 31
      May 2006. RESULTS: The highest number of cases in the 5 years concerned occurred
      in May (29 cases). Although PE occurred most commonly in the spring (72 cases)
      and autumn (51 cases), the difference was statistically significant (P = .003).
      There were no case correlations with months and pressure, temperature, or
      humidity. However, there was a statistically significant positive correlation
      between case incidence and atmospheric pressure (r = 0.53, P < .0005) and
      humidity (r = 0.57, P < .0005). In terms of risk factors, seasonal distribution
      was not statistically significant as regards cases of embolism occurring for
      surgical or nonsurgical reasons (r = 0.588). CONCLUSION: In terms of the
      relationship between seasons and embolism cases, despite the determination of an
      insignificant positive correlation, a statistically significant positive
      correlation was determined between air pressure and humidity and case incidence.
      There is now a need for further wide-ranging prospective studies including
      various hematological parameters to clarify the correlation between PE and air
      pressure.

PMID- 19091267
TI  - Clinical characteristics of aortic aneurysm and dissection as a cause of sudden
      death in outpatients.
AB  - OBJECTIVE: To describe characteristics of nonhospitalized patients experiencing
      sudden death from aortic causes and compare with characteristics of patients
      experiencing nontraumatic, unexpected, outpatient death from other causes.
      METHODS: Retrospective case-control analysis of patients aged 18 to 65 years with
      nontraumatic, unexpected, outpatient cardiac arrest, emergency department (ED)
      resuscitation attempts, and autopsy-determined cause of death. Demographics,
      prodromal symptoms, and arrest characteristics were examined, and univariate
      comparisons between patients with aortic and those with nonaortic causes of death
      were performed. RESULTS: A total of 384 patients met inclusion criteria. Aortic
      pathology represented 4.4% of patients (12 dissections, 5 aneurysms). Preexisting
      aortic disease (n = 2) and antemortem suspicion of an aortic cause (n = 3) were
      uncommon. Patients with an aortic cause of death often had prodromal symptoms
      (53% 95% CI; 28%-77%) and hemopericardium (47% 95% CI; 23%-72%), were older, and
      were more likely to have a pulse in the ED, an arrest rhythm of pulseless
      electrical activity, and an arrest witnessed arrest by a medical provider.
      CONCLUSION: In this sample of outpatients with cardiac arrest from aortic
      disease, death was not instantaneous, and hemopericardium was common in many
      patients with dissection.

PMID- 19091268
TI  - Electrocardiographic monitoring in the hospitalized patient: a diagnostic
      intervention of uncertain clinical impact.
AB  - Electrocardiographic monitoring, also known as telemetry monitoring or cardiac
      monitoring, focuses on the detection of clinically significant dysrhythmia.
      Although electrocardiographic monitoring has advantages and is undoubtedly
      invaluable in certain patients, significant overuse of cardiac telemetry
      monitoring does occur. The impact of this inappropriate use increases the cost of
      healthcare and can delay the admission process, an unpleasant burden which the
      hospital and its patients must bear. In addition, the liberal use of monitoring
      in unnecessary situations may give the hospital staff a false sense of security
      and/or desensitize them to alarms. In many instances, electrocardiographic
      monitoring may not be necessary. This article will review the literature
      regarding inpatient telemetry and its impact; furthermore, we will suggest high
      yield criteria for its application among the inpatient population.

PMID- 19091269
TI  - Five simple steps to improve an emergency physician's efficiency.

PMID- 19091270
TI  - Is there an alternative to mouth-to-mouth breathing?

PMID- 19091271
TI  - To shock or not to shock.

PMID- 19091272
TI  - Efficacy of low-dose snake antivenom in severe neurotoxic snake envenoming.

PMID- 19091273
TI  - ED management of pediatric syncope.

PMID- 19091274
TI  - Effect of sample volume for the measurement of osmolality by using the Advanced
      3250 osmometer.

PMID- 19091276
TI  - Frequent visits with urinary symptoms: subtle signs of ketamine abuse.

PMID- 19091275
TI  - Wheezy patient with heart failure and chronic obstructive pulmonary disease: what
      to treat with?

PMID- 19091277
TI  - Ultrasound-guided interscalene block for shoulder dislocation reduction in the
      ED.

PMID- 19091278
TI  - An unusual cause of abdominal pain: implications for infection control in the ED.

PMID- 19091279
TI  - Neck hyperflexion causing isolated thyroid cartilage fracture--a case report.
AB  - Isolated thyroid cartilage fracture is very rare, and most cartilage fractures
      are caused by direct impact to the laryngotracheal complex of the neck. Isolated
      thyroid cartilage fracture caused by hyperflexion of the neck has not been
      reported before. We present a case where an unrestrained front seat car passenger
      struck his forehead on the windshield during a motor vehicle accident. Direct
      impact of his forehead with sudden and forceful flexion of his neck caused
      isolated thyroid cartilage fracture without direct impact to the neck. Therefore,
      injury to the thyroid cartilage should be kept in the list of detailed evaluation
      with high index of suspicion in patients presenting with trauma mechanism
      possibly causing neck hyperflexion, even without signs of direct neck trauma.

PMID- 19091280
TI  - Acute splenic sequestration in an adult with hemoglobin S-C disease.
AB  - Acute splenic sequestration crisis is a common, potentially life-threatening
      complication of sickle cell anemia in children that is uncommon in adults.We
      present the case of a 44-year-old gentleman with undiagnosed hemoglobin S-C
      disease who developed intense back pain, marked abdominal distension, systemic
      inflammatory response syndrome, and multisystem organ failure that first
      presented as acute splenic sequestration crisis. The hemoglobinopathy SC is a
      disease caused by heterozygous-globin chain mutations with over-lapping clinical
      features of sickle cell disease with changes in the frequency of these
      manifestations reflected by the combination of characteristics of hemoglobin C
      and hemoglobin S. In hemoglobin S-C disease, autosplenectomy is rare and
      splenomegaly usually persists until adulthood;vasoocclusive complications are
      seen less habitually and become evident at a later time compared with sickle cell
      disease. The diagnosis of hemoglobin S-C disease is essentially done by
      exclusion. Transfusion of red blood cells is the treatment of choice, but
      splenectomy is indicated if transfusion therapy fails. A review of the literature
      and keypoints for the emergency practitioner are included.

PMID- 19091281
TI  - Multiple lacerations in a pregnant woman caused by spontaneously exploding shower
      screen glass.
AB  - Injuries caused by glass occur frequently, in particular in children, and make up
      an estimated 3% to 5% of all emergency visits, most frequently involving
      lacerations of hands, feet, and face. About 30% to 40% of glass injuries occur at
      home and often involve so-called architectural glass or bottles and glass
      containers. Accidents reported in association with showering mostly refer to
      falls or scalding by hot water. However, an increasing number of shower screens
      are made of tempered glass, which may potentially brake. Such injuries may be
      potentially severe, causing laceration of extremity arteries; requiring
      hospitalization or outpatient treatment for injuries; causing absence from work.
      These injuries are likely underreported in the medical literature but could have
      potential medicolegal consequences for the patient. We report a case of multiple
      lacerations developed in a third-trimester pregnant woman caused by the
      spontaneous shattering of a shower screen glass and discuss the apparent
      unawareness to this potential hazard in the scientific literature.

PMID- 19091282
TI  - Successful treatment of gastric perforation with thyrotoxic crisis.
AB  - Patients with thyrotoxic crisis presenting with another emergency are at a
      considerable risk. We report the successful treatment of a 55-year-old woman
      having gastric perforation with thyrotoxic crisis; the principle of treatment was
      delayed surgery after rapid preoperative restoration of thyroid function and
      cardiovascular status. The patient was admitted for severe abdominal pain and
      nausea with delirium, exophthalmos, diffuse goiter, tremulousness, diaphoresis,
      tabescence, pretibial edema, and atrial fibrillation. Computed tomography
      revealed free air over the liver surface. She had been diagnosed with
      uncontrolled hyperthyroidism 3 days before admission, with a free liothyronine
      (T(3)) of 23.2 pg/mL, a free levothyroxine sodium (T(4)) of greater than 7.78
      ng/dL, and thyrotropin of less than 0.01 ng/mL. She was diagnosed with
      gastroduodenal perforation and thyrotoxic crisis, and we planned nonoperative
      management comprising nasogastric aspiration, cefmetazole sodium, omeprazole,
      thiamazole, and Lugol's solution. We also used landiolol, an ultrashort-acting
      beta(1)-adrenoceptor antagonist, and hydrocortisone. On the third day of
      admission, her thyroid function had improved with a free T(3) of 4.7 pg/mL and a
      free T(4) of 2.9 ng/dL; however, perforative peritonitis had worsened, and hence,
      omental patch repair was performed. She recovered uneventfully and was discharged
      after radioiodine administration. We discuss the management of a thyrotoxic
      patient with gastric perforation and focus on the importance of changing the
      management according to the patient's clinical course considering his thyroid
      function status and comparing the stress of surgery with that of perforative
      peritonitis in nonoperative management.

PMID- 19091283
TI  - A single implantable cardioverter-defibrillator shock unmasking an electrical
      storm of 389 ventricular tachycardia episodes triggering device therapies.
AB  - We describe the case of a patient with ischemic cardiomyopathy who presented the
      first implantable cardioverter-defibrillator (ICD) shock approximately 5 months
      after implantation. Device interrogation surprisingly revealed the occurrence of
      389 ventricular tachyarrhythmia episodes terminated by asymptomatic
      antitachycardia pacing (ATP) except for the episode requiring shock. The present
      case of electrical storm highlights how contemporary tiered ATP schemes
      constitute a valuable but underused form of termination for ventricular
      tachyarrhythmias in ICD patients, reducing the number of painful shocks and their
      adverse consequences.

PMID- 19091284
TI  - Multiple cardiac thrombi and thromboembolism in a heparin-induced
      thrombocytopenia antibody-positive patient with heart failure.
AB  - A 49-year-old Japanese man presented with orthopnea and edema in both legs. He
      was diagnosed with congestive heart failure with triple-vessel coronary artery
      disease. Low antithrombin and left ventricular systolic dysfunction were possible
      causes of his hypercoagulable state. Echocardiography revealed thrombi in the
      left ventricle and left trium, poor left ventricular contractility, and a normal
      mitral valve. Electrocardiogram revealed normal sinus rhythm. We found small
      infarctions of the brain and spleen in the computed tomography. The heparin
      treatment of cardiac thrombi is useless because the patient had heparin-induced
      thrombocytopenia antibody. We removed thrombi in the left ventricle and left
      atrium by thrombectomy and performed coronary artery bypass graft. Warfarin was
      administered for anticoagulation. He recovered completely and is now doing well.
      Our experience indicates that poor cardiac function can together cause multiple
      cardiac thrombi and subsequent thromboembolism without mitral stenosis or atrial
      fibrillation.

PMID- 19091285
TI  - Ruptured aortic aneurysm masquerading as phlegmasia cerulea.
AB  - Phlegmasia cerulea dolens, characterized by the triad of limb swelling, cyanosis,
      and acute ischemic pain, usually arises because of acute massive thrombosis of
      major deep, collateral, and superficial veins of an extremity. We report a
      patient with an atypically presenting ruptured aortic aneurysm masquerading as
      phlegmasia cerulea dolens. A 68-year-old man with a history of hypertension,
      intermittent claudication, and smoking presented with asthenia, macrohematuria,
      and mild back pain, as well as edema and blue mottling of the lower limbs and
      abdomen for 24 hours. The abdomen was nontender without a pulsatile mass or
      murmur. Computed tomography showed an 85-mm abdominal aortic aneurysm ruptured
      into the inferior vena cava. Phlegmasia cerulea dolens-like symptoms were
      explained by compromised venous outflow from the lower limbs because of an
      aortocaval fistula. The patient died of uncontrollable hemorrhage during emergent
      surgical repair. Three percent to 6% of patients with abdominal aortic aneurysm
      rupture present an aortocaval fistula, which can be suspected by the triad of
      abdominal or lower back pain, pulsatile abdominal mass, and machinery-type
      abdominal murmur. Left untreated, this condition rapidly leads to death from
      congestive heart failure. Only one third of patients are diagnosed before surgery
      because a fistula is often not suspected until unexplained massive hemorrhage
      occurs during the operation. Operative mortality is extremely high (34%). We
      propose that the clinical syndrome presented by our patient, a "blue fistula"
      frequently associated with aortocaval fistulae, be called phlegmasia cerulea non
      dolens, by analogy to Gregoire's "blue phlebitis."

PMID- 19091286
TI  - Leech bites: massive bleeding, coagulation profile disorders, and severe anemia.
AB  - Leeches have been in use for centuries, especially in plastic and reconstructive
      surgery wound and flap healing, in venous insufficiencies, and in the treatment
      of many disorders such as hemorrhoids and varicosity. With this study, we aimed
      to discuss coagulation disorder due to uncontrolled leech bites, consequent
      excessive skin hemorrhage, and anemia requiring blood transfusion. A 65-year-old
      male patient was referred to the emergency department because of excessive
      intractable bleeding that had occurred after leech bites. On physical
      examination, a total of 130 bites were detected on various regions of the body.
      In the laboratory findings of the patient, hemoglobin and hematocrit levels were
      extremely low, and prothrombin time, international normalized ratio, and partial
      thromboplastin time were markedly increased. The patient received a total of 8
      units of fresh frozen plasma and 6 units of erythrocyte suspension. Bleeding
      stopped by decreasing after the transfusion of fresh frozen plasma. Although the
      complications due to leech injuries are rare, they may be an important cause of
      morbidity and mortality when an injury or prolonged bleeding in an internal
      region occurs. Prolonged skin hemorrhages rarely cause anemia, and deaths are
      caused by intractable hemorrhages. However, a coagulation disorder and consequent
      intractable hemorrhage have not been reported previously in the literature. In
      conclusion, it should be known that uncontrolled, blind, and excessive leech use
      causes severe hemorrhage and excessive blood loss, causing significant morbidity
      and mortality. Therefore, the awareness of either physicians or people using or
      recommending alternative medicine should be raised on this subject.

PMID- 19091287
TI  - Pituitary apoplexy associated with cortisol-induced hyperglycemia and acute
      delirium.
AB  - Pituitary apoplexy indicates pituitary adenoma hemorrhage, which could result in
      acute pituitary insufficiency and mortality. The typical symptoms are headache,
      visual disturbance, nausea, vomiting, altered mental status, and
      panhypopituitarism. However, cortisol-induced hyperglycemia and acute delirium
      could be an initial presentation of a pituitary adenoma hemorrhage with stormy
      release of the adrenocorticotrophic hormone. A 28-year-old woman presented with
      severe vomiting, irritable state, and delusion. She had medical history of
      irregular menstrual cycles and marked body weight gain after her second
      childbirth 8 years ago. She was diagnosed of diabetic ketoacidosis 2 days before
      this visiting at local medical department. On physical examination, Cushing
      appearance without definite neurological deficit was disclosed. Further blood
      tests revealed high blood sugar, cortisol, and adrenocorticotrophic hormone
      levels without evidence of diabetic ketoacidosis. The brain computed tomography
      and magnetic resonance imaging showed pituitary macroadenoma and pituitary
      hemorrhage. Cushing disease with pituitary apoplexy was then diagnosed.
      Conservative management with delayed neurosurgery was applied. The patient became
      clear with normalized cortisol and blood sugar levels soon after. Follow-up
      computed tomography scan of the brain revealed no progression of tumor bleeding
      or mass effect. To our knowledge, pituitary apoplexy associated with cortisol
      induced hyperglycemia and acute delirium has never been reported before. This
      case reminds us of pituitary apoplexy and its rare manifestations.

PMID- 19091288
TI  - Successful prolonged resuscitation involving the use of tenecteplase without
      neurological sequelae.
AB  - Prehospital cardiac arrest is associated with a very poor prognosis. We report a
      case of complete neurological recovery after prolonged resuscitation involving
      the use of tenecteplase in a patient with undifferentiated cardiac arrest with a
      return of spontaneous circulation after 1 hour of resuscitation, where basic life
      support was commenced immediately by a bystanding family member. Factors
      associated with an increased chance of survival from out-of-hospital cardiac
      arrest are discussed as well as the role of thrombolytics in cardiopulmonary
      resuscitation.

PMID- 19091289
TI  - Serotonin syndrome in a patient taking Lexapro and Flexeril: a case report.
AB  - The serotonin syndrome is a rare toxicological emergency increasingly seen in
      emergency practice, secondary to increased use of proserotinergic drugs. In this
      case report, the condition is described in a patient taking the selective
      serotonin reuptake inhibitor Lexapro and the muscle-relaxant Flexeril. Based on
      this case, Cyclobenzaprine should be considered on the growing list of
      medications that can precipitate the serotonin syndrome. With the increasing
      prevalence of proserotinergic polypharmacy, this uncommon toxidrome should be
      considered by the alert emergency medicine physician.

PMID- 19091290
TI  - Acute ataxia in a 4-year-old boy: a case of Lyme disease neuroborreliosis.
AB  - We present a case of a 4-year-old who presented to the emergency department with
      an unsteady gait for 2 days. Ataxia is a rare but known manifestation of
      cerebellar involvement in Lyme disease. A 4-year-old (17 kg) boy with no
      significant medical history presented to the emergency department (ED) with
      history of nonbloody emesis for 2 weeks and an unsteady gait for 2 days. Over the
      past 2 days, his gait had gotten progressively worse until he was unable to walk
      without assistance. The vomiting would usually occur 1 hour after eating meals.
      He had also complained of a single headache, which occurred approximately 10 days
      before admission. The headache did not occur in the early morning hours or wake
      him up from his sleep. His appetite for the weeks before admission had
      progressively decreased, and he had also become more irritable, especially when
      stimulated. He had increased fatigue for the week before presentation. His
      parents denied any fever, rhinorrhea, cough, diarrhea, rash, bruising, bleeding,
      or hematuria. The patient denied any abdominal pain or headache while in the ED.

PMID- 19091291
TI  - Effectiveness of hemodialysis in acute dapsone overdose-a case report.
AB  - The use of dapsone is increasing even though overdose is rarely reported and
      physicians must be aware of its toxicity and management. Mortality can occur due
      to methemoglobinemia and hemolytic anemia. Although activated charcoal and
      methylene blue are recommended, the use of hemodialysis is reported only in few
      studies. Literature on the kinetic profile indicates that 50% to 80% of dapsone
      is protein bound and indicates a possibility to dialyze the unbound form. This
      study describes a case of deliberate severe dapsone overdose with cyanosis,
      methemoglobinemia, and hemolytic anemia, which improved after repetitive
      hemodialysis.

PMID- 19091292
TI  - A rare case of massive retroperitoneal hemorrhage after bone marrow aspiration
      alone.
AB  - The use of dapsone is increasing even though overdose is rarely reported and
      physicians must be aware of its toxicity and management. Mortality can occur due
      to methemoglobinemia and hemolytic anemia. Although activated charcoal and
      methylene blue are recommended, the use of hemodialysis is reported only in few
      studies. Literature on the kinetic profile indicates that 50% to 80% of dapsone
      is protein bound and indicates a possibility to dialyze the unbound form. This
      study describes a case of deliberate severe dapsone overdose with cyanosis,
      methemoglobinemia, and hemolytic anemia, which improved after repetitive
      hemodialysis.

PMID- 19091293
TI  - A floating thrombus of the right ventricle in severe massive pulmonary embolism.
AB  - Floating right heart thrombus (FRHT) is a severe presentation of thromboembolic
      disease and usually coexists with massive pulmonary embolism. Patients with FRHT
      are more hemodynamically compromised and usually have a higher mortality rate
      than patients without FRHT. An echocardiographic finding of FRHT is important
      because it identifies as poor prognosis. The optimal treatment in patients with
      FRHT remains uncertain. Heparin is more often an anticoagulant than a lytic
      agent. Several studies suggested that thrombolytic therapy has advantages in
      treating such patients. Early diagnosis and emergency therapy are important in
      treating patients with FRHT in the emergency department and they might have fatal
      outcomes when treated only with heparin.

PMID- 19091294
TI  - Perforated peptic ulcer associated with abdominal compartment syndrome.
AB  - Abdominal compartment syndrome (ACS) is defined as an increased intra-abdominal
      pressure with adverse physiologic consequences. Abdominal compartment syndrome
      caused by perforated peptic ulcer is rare owing to early diagnosis and
      management. Delayed recognition of perforated peptic ulcer with pneumoperitoneum,
      bowel distension, and decreased abdominal wall compliance can make up a vicious
      circle and lead to ACS. We report a case of perforated peptic ulcer associated
      with ACS. A 74-year-old man with old stroke and dementia history was found to
      have distended abdomen, edema of bilateral legs, and cyanosis. Laboratory tests
      revealed deterioration of liver and kidney function. Abdominal compartment
      syndrome was suspected, and image study was arranged to find the cause. The study
      showed pneumoperitoneum, contrast stasis in heart with decreased caliber of
      vessels below the abdominal aortic level, and diffuse lymphedema at the abdominal
      walls. Emergent laparotomy was performed. Perforated peptic ulcer was noted and
      the gastrorrhaphy was done. The symptoms, and liver and kidney function improved
      right after emergent operation.

PMID- 19091295
TI  - Forestier disease: an unusual cause of upper airway obstruction.
AB  - We report the case of a 75-year-old man who presented at the emergency department
      complaining of difficult breathing, especially when in supine position. He had
      cough, dysphonia, and dysphagia for fluids in the last few months. After ruling
      out other causes of dyspnea, a lateral cervical radiograph was performed that
      showed large osteophytes compressing the airway, which was confirmed by cervical
      computed tomography. Marked improvement of symptoms was observed after resection
      of the osteophytes compressing the airway. Diffuse idiopathic skeletal
      hyperostosis, or Forestier disease, is an ossifying disease of ligaments and
      tendons and affects mainly elderly men. Anterior longitudinal ligament
      ossification is characteristic. Although it is asymptomatic in some occasions,
      the disease may produce dysphagia, dysphonia, and exceptionally breathing
      difficulties due to airway compromise. In these cases, early surgery is
      recommended to alleviate airway obstruction.

PMID- 19091296
TI  - Spinal cord arteriovenous malformation in a toddler presenting with altered
      mental status and fever.
AB  - Central nervous system arteriovenous malformations (AVMs) are a rare cause of
      subarachnoid hemorrhage and neurologic deficits. About 90% of these lesions are
      supratentorial, with a smaller percentage occurring in the posterior fossa and an
      even smaller number found throughout the spine. Although spinal AVMs are
      uncommon, these disorders represent a treatable cause of significant morbidity in
      a young age group. We report a case of a T11-T12 spinal AVM in a 14-month-old
      girl presenting with low-grade fever and lethargy who was found to have
      subarachnoid hemorrhage on evaluation and describe a reasonable stepwise approach
      to these patients in the emergency department utilizing computed tomography,
      lumbar puncture, magnetic resonance imaging, and angiography.

PMID- 19091297
TI  - Noninvasive blood pressure cuff causing humerus fracture.
AB  - Blood pressure recording is a part of the routine set of initial observations for
      any patient. It is performed by variety of medical and paramedical personnel
      universally. Bone metastases and pathologic fracture of the bone are common in
      the elderly patient. Noninvasive blood pressure recording is innocuous procedure,
      although on rare occasions can cause iatrogenic fracture of the asymptomatic
      pathologic bone. This case report highlights the importance of vigilance to look
      for pain and tender area over the site of blood pressure cuff placement and
      before its inflation to record blood pressure, as it can be "traumatic" for the
      asymptomatic weak pathologic bone leading to a fracture. Iatrogenic fracture can
      add to the burden of a patient's medical problem, necessitating secondary
      surgical procedure, delaying recovery, and having the possibility of medicolegal
      problems.

PMID- 19091298
TI  - A case of acute toxic hepatitis after suicidal chloroform and dichloromethane
      ingestion.
AB  - Chloroform and dichloromethane are halogenated hydrocarbons that have been used
      as a potent anesthetic agent or a general industrial solvent. Short-term exposure
      to chloroform anesthesia and long-term exposure to chloroform and dichloromethane
      in workplaces can produce adverse health effects, such as hepatitis, cardiac
      arrhythmia, and carbon monoxide intoxication. Most of the related reports,
      however, involve the inhalation of such substances by humans. Limited reports are
      available regarding the adverse clinical effects of these substances in the case
      of a person's immediate ingestion of them. A 23-year-old man with an altered
      mental status after attempting suicide through the oral ingestion of unknown
      chemicals was brought to the emergency department (ED). We identified that the
      patient was poisoned with chloroform and dichloromethane by analysis of contents
      of the suspected chemicals in the bottle through gas chromatography. Abnormal
      liver enzymes were noted on postingestion day 2, and jaundice occurred on
      postingestion day 3. The radiologic findings from computed tomographic (CT)
      scanning showed severe fatty infiltration of the liver parenchyma. The patient
      received supportive cares and was restored to health from hepatic dysfunction and
      was discharged without complications after 2 weeks of admission.

PMID- 19091299
TI  - Technical evaluation of the first fully automated assay for the detection of TSH
      receptor autoantibodies.
AB  - BACKGROUND: Graves' disease (GD) is mediated by autoantibodies which bind to the
      TSH receptor (TRAb). The aim of the present study was to evaluate the technical
      performance of the first fully automated immunoassay for TRAb detection. METHODS:
      The Elecsys Anti-TSHR immunoassay utilizes a porcine TSH receptor (TSHR) and the
      human thyroid stimulating monoclonal TSHR autoantibody M22. RESULTS: Intraassay
      and total imprecision CV were determined between 1.4%-14.9%, and 2.4%-28.8%,
      respectively. Using the 20% CV criteria the functional sensitivity was found at
      0.73 IU/L. The median CV at the cut-off (1.75 IU/L) was found to be 11%.
      Comparison studies with five TRAb immunoassays yielded slopes and intercepts
      between 1.02-1.48, and -0.74-0.56, respectively. Correlation coefficients were
      determined between 0.895 and 0.978. ROC plot analysis of patients with GD,
      patients with other thyroid disorders and healthy controls revealed an AUC of
      0.99 resulting in a sensitivity of 97% and a specificity of 99% at a TRAb level
      of 1.75 IU/L. CONCLUSION: The evaluation of the TRAb immunoassay generated
      homogeneous performance data and demonstrated a high degree of comparability to
      established TRAb assays. The automated TRAb assay represents a major improvement
      of thyroid testing in clinical practice.

PMID- 19091300
TI  - Age-dependent morphine intake and cue-induced reinstatement, but not escalation
      in intake, by adolescent and adult male rats.
AB  - Despite increasing rates of opioid abuse by human adolescents, few laboratory
      experiments address adolescent vulnerability to opiates. We examined intravenous
      morphine self-administration after adolescent- vs. adult-onset, followed by
      extinction and cue-induced reinstatement. Adolescent male Sprague-Dawley rats
      [postnatal day (P) 35 at start] and adults (P91) acquired lever pressing
      maintained by 0.375 mg/kg/infusion morphine on a fixed ratio one schedule of
      reinforcement. Subjects were subsequently divided into short or long daily access
      conditions (ShAcc, 1-h vs. LgAcc, 8-h; 18 sessions). After extinction, cue
      induced reinstatement was recorded over 1 h. During the first six 1-h acquisition
      sessions and continuing throughout ShAcc conditions, adolescent-onset rats self
      administered less morphine than adults, an effect commonly interpreted as higher
      drug sensitivity. In contrast under LgAcc conditions, escalation of morphine
      intake was similar across ages. Extinction of drug-seeking was similar across
      ages, although rats from LgAcc conditions pressed more than ShAcc conditions.
      Notably, cue-induced reinstatement was less robust in rats that began morphine
      self-administration during adolescence vs. adulthood. Although increased
      sensitivity of younger rats to morphine reinforcement under ShAcc conditions
      might help explain opioid abuse by human adolescents, lower rates of
      reinstatement in younger rats might suggest that adolescent development includes
      some protective factors that dampen the long-term impact of early drug intake.

PMID- 19091302
TI  - Expression of neuronal calcium sensor-1 (NCS-1) is decreased in leukocytes of
      schizophrenia and bipolar disorder patients.
AB  - Schizophrenia (SCZ) and bipolar disorder (BPD) are severe illnesses representing
      an enormous social, familiar and individual burden that affect 1% of the
      population world-wide. Several evidences indicate abnormalities of the dopamine
      system in both SCZ and BPD. Neuronal calcium sensor-1 (NCS-1) is a protein that
      has many functions in neurotransmission such as inhibition of dopamine D(2)
      receptor desensitization, regulation of ionic channels and enhancement of
      exocytosis of neurotransmitters. In addition, NCS-1 protein expression and mRNA
      levels were found increased in pre-frontal cortex (PFC) of SCZ and BPD patients.
      NCS-1 expression in neural and neuroendocrine cells is well documented and,
      recently, it was shown that NCS-1 is also expressed in mast cells and
      neutrophils. NCS-1 has important functions in mast cells since it stimulates Fc
      epsilon RI-triggered exocytosis and the release of arachidonic acid metabolites.
      Then, due to the known close relation between the nervous and immune systems, we
      sought to investigate the NCS-1 expression in lymphocytes and monocytes (CD4+ T
      lymphocytes, CD56+ NK cells, CD19+ B lymphocytes and CD14+ monocytes) of SCZ and
      BPD patients. Using flow cytometry, our results have shown that NCS-1 expression
      was diminished in CD4+T lymphocytes, CD19+ B lymphocytes and CD14+ monocytes of
      BPD patients and also decreased in CD4+ T lymphocytes and CD56+ NK cells of SCZ
      patients. Results suggest that immune cells might be a cellular model for studies
      with SCZ and BPD patients considering NCS-1 functions. Efforts need to be done to
      investigate the motive of the decreased percentage of immune cells expressing NCS
      1 in patients with SCZ and BPD.

PMID- 19091301
TI  - Pharmacotherapy for adults with tumors of the central nervous system.
AB  - Tumors of the adult central nervous system are among the most common and most
      chemoresistant neoplasms. Malignant tumors of the brain and spinal cord
      collectively account for approximately 1.3% of all cancers and 2.2% of all cancer
      related deaths. Novel pharmacological approaches to nervous system tumors are
      urgently needed. This review presents the current approaches and challenges to
      successful pharmacotherapy of adults with malignant tumors of the central nervous
      system and discusses novel approaches aimed at overcoming these challenges.

PMID- 19091304
TI  - Food groups and endometrial cancer risk: a case-control study from Italy.
AB  - OBJECTIVE: Although several studies have been conducted on the relation between
      dietary habits and endometrial cancer risk, the evidence for specific food groups
      is still controversial. STUDY DESIGN: We analyzed data from an Italian case
      control study including 454 women with histologically confirmed endometrial
      cancer and 908 controls admitted to the same hospitals for acute, nonneoplastic
      conditions. Multivariate odds ratios (ORs) were obtained after allowance for
      major potential confounding factors. RESULTS: A significant increase in risk was
      observed for red meat, with an OR of 2.07 for an increment of 1 serving per day.
      Inverse associations were observed for coffee (OR, 0.83), cereals (OR, 0.92), and
      vegetables (OR, 0.83). CONCLUSION: Our results support the existence of a
      relation between dietary habits and endometrial cancer risk and in particular
      suggest that a diet rich in red meat and poor in vegetables may have an
      unfavorable effect.

PMID- 19091305
TI  - Concurrent cisplatin-based chemoradiation International Federation of Gynecology
      and Obstetrics stage IB2 cervical carcinoma.
AB  - OBJECTIVE: The objective of the study was to assess the effectiveness of primary
      chemoradiation for stage IB(2) cervical carcinoma. STUDY DESIGN: A retrospective
      study of patients treated with primary chemoradiation at selected hospitals in
      Cleveland, OH, from 1992 to 2006 was performed. Patients with regional or distant
      metastasis on pretreatment imaging were excluded. Patients received pelvic
      teletherapy with weekly concurrent cisplatin and high- or low-dose-rate
      brachytherapy. RESULTS: Forty-nine patients with a median age of 51 years were
      identified. The majority of patients were white (81.6%) and had squamous cell
      carcinomas (81.6%) and a median tumor diameter of 5 cm (range, 4.1-10 cm). The
      median duration of follow-up was 41 months. Progression of disease was observed
      in 10 (20.4%) patients. The local control rate was 86%. At 36 months, the
      progression-free survival (PFS) was 79% and the overall survival (OS) was 86%.
      CONCLUSION: Primary chemoradiation has a high clinical response rate, PFS, and OS
      for women with stage IB(2) cervical cancer.

PMID- 19091306
TI  - Objective evaluation of interior noise booming in a passenger car based on sound
      metrics and artificial neural networks.
AB  - Booming sound is one of the important sounds in a passenger car. The aim of the
      paper is to develop the objective evaluation method of interior booming sound.
      The development method is based on the sound metrics and ANN (artificial neural
      network). The developed method is called the booming index. Previous work
      maintained that booming sound quality is related to loudness and sharpness--the
      sound metrics used in psychoacoustics--and that the booming index is developed by
      using the loudness and sharpness for a signal within whole frequency between 20
      Hz and 20 kHz. In the present paper, the booming sound quality was found to be
      effectively related to the loudness at frequencies below 200 Hz; thus the booming
      index is updated by using the loudness of the signal filtered by the low pass
      filter at frequency under 200 Hz. The relationship between the booming index and
      sound metric is identified by an ANN. The updated booming index has been
      successfully applied to the objective evaluation of the booming sound quality of
      mass-produced passenger cars.

PMID- 19091303
TI  - Protein scaffolds in MAP kinase signalling.
AB  - The mitogen-activated protein kinase (MAPK) pathway allows cells to interpret
      external signals and respond in an appropriate way. Diverse cellular functions,
      ranging from differentiation and proliferation to migration and inflammation, are
      regulated by MAPK signalling. Therefore, cells have developed mechanisms by which
      this single pathway modulates numerous cellular responses from a wide range of
      activating factors. This specificity is achieved by several mechanisms, including
      temporal and spatial control of MAPK signalling components. Key to this control
      are protein scaffolds, which are multidomain proteins that interact with
      components of the MAPK cascade in order to assemble signalling complexes. Studies
      conducted on different scaffolds, in different biological systems, have shown
      that scaffolds exert substantial control over MAPK signalling, influencing the
      signal intensity, time course and, importantly, the cellular responses. Protein
      scaffolds, therefore, are integral elements to the modulation of the MAPK network
      in fundamental physiological processes.

PMID- 19091307
TI  - Towards a framework to select techniques for error prediction: supporting novice
      users in the healthcare sector.
AB  - Whilst healthcare has increased its awareness of the retrospective safety
      assessment techniques, such as root cause analysis, adoption of the corresponding
      predictive safety assessment techniques has been slow and sporadic. Reasons for
      this may include lack of support in technique choice and practical knowledge in
      the published literature. Whilst there have been many publications on these
      techniques, few have aimed to support the novice user in selecting a technique
      from the broad array of choice to facilitate targeting of education in techniques
      for specific purposes. This paper aims to address this through collecting an
      evidence base towards developing a bottom-up (resources and constraints) and top
      down (requirements) approach to technique selection. Conclusions indicate there
      is a lack of practical experiences described in the literature to conclusively
      define a technique for selection and a need for a dedicated research in this area
      to make it accessible for healthcare and other novice users.

PMID- 19091308
TI  - Reducing depressive intrusions via a computerized cognitive bias modification of
      appraisals task: developing a cognitive vaccine.
AB  - A feature of depression is the distressing experience of intrusive, negative
      memories. The maladaptive appraisals of such intrusions have been associated with
      symptom persistence. This study aimed to experimentally manipulate appraisals
      about depressive intrusions via a novel computerized cognitive bias modification
      (CBM) of appraisals paradigm, and to test the impact on depressive intrusion
      frequency for a standardized event (a depressive film). Forty-eight participants
      were randomly assigned to either a session of positive or negative CBM.
      Participants then watched a depressing film (including scenes of bereavement and
      bullying) and subsequently monitored the occurrence of depressive intrusions
      related to the film in a diary for one week. At one-week follow-up, participants
      completed additional measures of intrusions--the Impact of Event Scale (IES) and
      an intrusion provocation task. As predicted, compared to the negative condition,
      participants who underwent positive CBM showed a more positive appraisal bias.
      Further, one week later, positive CBM participants reported fewer intrusions of
      the film and had lower IES scores. Our findings demonstrate that it is possible
      to manipulate maladaptive appraisals about depressive intrusions via a
      computerized CBM task. Further, this effect transfers to reducing intrusive
      symptomatology related to a standardized event (a depressive film) over one week,
      suggesting novel clinical implications.

PMID- 19091309
TI  - Preparation and physical properties of chitin fatty acids esters.
AB  - Trifluoroacetic anhydride is an effective promoter for the preparation of chitin
      single- and mixed-acid esters. Complete dissolution is achieved within 30 min
      when powdered chitin is heated at 70 degrees C in a mixed solution of carboxylic
      acid(s) and trifluoroacetic anhydride. Chitin esters prepared are chitin acetate,
      chitin butyrate, chitin hexanoate and chitin octanoate, chitin co
      acetate/butyrate, chitin co-acetate/hexanoate, chitin co-acetate/octanoate,
      chitin co-acetate/palmitate, each from a solution of the respective reactants.
      The products have degrees of O-acyl substitution in a range of DS 1-2 depending
      on the nature of acyl group, as analyzed by gas-liquid and high-pressure liquid
      chromatography. Acetic acid as a mutual component for the mixed-acid esters
      increases the total degree of substitution, and the acetyl substitution is close
      to the relative distribution in the reaction mixture for chitin co
      acetate/butyrate. It is favored over hexanoate, octanoate, and palmitate. The
      parent molecules, as calculated by the composition of the chitin esters and their
      molecular weights by light-scattering spectroscopy, are 30 kDa for the smallest
      and 150-151 kDa for the largest. Films of these chitin derivatives when cast from
      solution are strong and flexible with limited extensibility. By dynamic
      mechanical analysis of the ester film, it was found that both the glass
      transition temperature (T(g)) and the tensile modulus (E' at 25 degrees C) are
      highest for chitin acetate (218 degrees C and 5.8 GPa), and lowest for chitin
      octanoate (182 degrees C and 1.5 GPa). For the other esters, these values lie
      between the above-cited values, where the T(g) and the E' decrease with an
      increase in the chain length of the acyl constituent.

PMID- 19091310
TI  - Activin A down-regulates the phagocytosis of lipopolysaccharide-activated mouse
      peritoneal macrophages in vitro and in vivo.
AB  - Activin A is a multifunctional factor of the transforming growth factor-beta (TGF
      beta) superfamily and acts as an anti-inflammatory cytokine produced by microglia
      and macrophages. In this study, we investigated the regulatory effect and
      possible mechanism of activin A on activation of lipopolysaccharide (LPS)-induced
      mouse peritoneal macrophages. The results showed that activin A could decrease NO
      release in LPS-activated mouse peritoneal macrophages, and suppressed
      phagocytosis and pinocytosis of mouse peritoneal macrophages stimulated by LPS in
      vitro and in vivo. Furthermore, activin A remarkably inhibited the expressions of
      CD14 and MHC II on LPS-induced mouse peritoneal macrophages, but had no
      significant effect on the expression of MHC I and the proliferation of mouse
      peritoneal macrophages. These findings suggest that activin A can down-regulate
      inflammatory mediator production and phagocytosis of LPS-activated macrophages
      via suppressing CD14 expression, and may influence the presentation of exogenous
      antigens via inhibiting MHC II expression. Thus, activin A might have the
      potential for treatment of macrophage-mediated inflammatory diseases through
      modulating both innate and adaptive immune responses.

PMID- 19091311
TI  - Frequency trajectory effects in Chinese character recognition: evidence for the
      arbitrary mapping hypothesis.
AB  - Frequency trajectory is a better measure to investigate age-limited learning
      effects than age of acquisition (AoA) ratings (Zevin, J. D., & Seidenberg, M. S.
      (2002). Age of acquisition effects in word reading and other tasks. Journal of
      Memory and Language, 47(1), 1-29). The current study uses frequency trajectory as
      a variable to investigate age-limited learning effects in Chinese character
      recognition, and tests predictions of the arbitrary mapping hypothesis as applied
      in a non-alphabetic writing system. In Experiment 1, regression analyses showed
      that, compared to rated AoA, frequency trajectory of characters was less affected
      by other lexical properties, and could explain a significant proportion of
      variance of AoA. In Experiment 2, the frequency trajectory and predictability
      from orthography to pronunciation of characters were orthogonally manipulated in
      a character naming task. The frequency trajectory effect appeared only for the
      arbitrary mapping condition. In Experiment 3, frequency trajectory and
      predictability from orthography to meaning of characters were manipulated in a
      semantic category judgment task. The frequency trajectory effects were found only
      when the mapping from orthography to semantic is less consistent. In summary, the
      study confirmed that AoA is a genuine factor affecting word processing, and the
      AoA effects were limited to those situations in which mapping between input and
      output representation was arbitrary. These results provide strong cross
      linguistic evidence in support of the arbitrary mapping hypothesis.

PMID- 19091312
TI  - Regulation of lens volume: implications for lens transparency.
AB  - Lens transparency is critically dependent on the maintenance of an ordered tissue
      architecture, and disruption of this order leads to light scatter and eventually
      lens cataract. Hence the volume of the fiber cells that make up the bulk of the
      lens needs to be tightly regulated if lens transparency is to be preserved. While
      it has long been appreciated that the lens can regulate its volume when placed in
      anisosmotic solutions, recent work suggests that the lens also actively maintains
      its volume under steady-state conditions. Furthermore, the process of fiber cell
      elongation necessitates that differentiating fiber cells dramatically increase
      their volume in response to growth factors. The cellular transport mechanisms
      that mediate the regulation of fiber cell volume in the lens cortex are only just
      beginning to be elucidated. In this region, fiber cells are continuously
      undergoing a process of differentiation that creates an inherent gradient of
      cells at different stages of elongation. These cells express different
      complements of transport proteins involved in volume regulation. In addition,
      transport processes at different depths into the lens are differentially
      influenced by electrochemical gradients that alter with distance into the lens.
      Taken together, our work suggests that the lens has spatially distinct ion influx
      and efflux pathways that interact to control its steady-state volume, its
      response to hypotonic swelling, and the elongation of differentiating fibers.
      Based on this work, we present a model which may explain the unique damage
      phenotype observed in diabetic cataract, in terms of the uncoupling or
      dysregulation of these ion influx and efflux pathways.

PMID- 19091313
TI  - Taiwanese women's experiences of becoming a mother to a very-low-birth-weight
      preterm infant: a grounded theory study.
AB  - BACKGROUND: Significant improvements have occurred in the survival rates of small
      preterm infants. As more infants survive their preterm birth, the number of
      parents associated with this experience has also increased. Clearly, the birth of
      very-low-birth-weight (VLBW) preterm infants poses considerable challenges for
      all mothers. These challenges are further compounded in Taiwan, where women are
      traditionally required to practise the cultural ritual (Zuo Yue Zi) which
      includes confinement to the house with a special balanced diet for the first
      month postnatally. Moreover, there is a deficit of information on mothers'
      experiences when their preterm infants are in neonatal intensive care units
      (NICUs). AIMS: The aim of this study was to explore Taiwanese mothers' (n=26)
      parenting experiences when their preterm infants were in NICUs. DESIGN: A
      qualitative research approach, grounded theory, was used to explore the mothers'
      lived reality of these experiences. METHODS: In-depth interviews and participant
      observations were conducted to gain insight into the experience of parenting.
      FINDINGS: A theoretical model was formulated from the findings delineating
      Taiwanese mothers' parenting experiences during their preterm infants stay in
      hospital. The findings indicated that the preterm birth, together with the
      admission of their infants to a NICU, presented mothers with an unexpected
      crisis. The particular cultural postnatal ritual posed this group of Taiwanese
      mothers with an additional difficulty in establishing physical interactions.
      However, the Taiwanese mothers created alternative channels of contact with their
      hospitalised infants using emotional connections, while the physical interactions
      were certainly limited. Despite all the difficulties this group of Taiwanese
      mothers faced and resolved, they all gradually captured and embraced the
      parenting role. The finding of this study further indicated that the support the
      mothers received from the healthcare professionals and the social networks the
      mothers made helped to create the connections that developed between the mothers
      and infants, making their journey towards parenthood possible. CONCLUSION: The
      theoretical model developed in this study is the first of its kind to contribute
      to the field of neonatal nursing in Taiwan. This would help Taiwanese women come
      to terms with becoming mothers of VLBW infants and subsequently enhance their
      parenting role.

PMID- 19091314
TI  - Albuminuria, metabolic syndrome and the risk of mortality and cardiovascular
      events.
AB  - AIM: Increased urinary albumin-excretion is a cardiovascular risk-factor. The
      cardiovascular risk of the metabolic syndrome (MetS) is debated. The aim of the
      present prospective, population-based study of non-diabetic individuals was to
      examine the association between low-grade urinary albumin-excretion, MetS, and
      cardiovascular morbidity and all-cause mortality. METHODS: 5215 non-diabetic, non
      proteinuric men and women participating in the Tromso Study 1994-1995 were
      included. Urinary albumin-creatinine ratio (ACR) was measured in three urine
      samples. The participants were categorized into four groups by the
      presence/absence of MetS (the International Diabetes Federation definition) and
      ACR in the upper tertile (>or=0.75 mg/mmol). RESULTS: Median follow-up time was
      9.6 years for first ever myocardial infarction, 9.7 years for ischemic stroke and
      12.4 years for mortality. High ACR (upper tertile)/MetS was associated with
      increased risk of myocardial infarction (hazard ratio (HR) 1.75; 95% confidence
      interval (CI): 1.30-2.37, p<0.001), stroke (HR 2.48; 95% CI: 1.66-3.71, p<0.001),
      and all-cause mortality (HR 1.63; 95% CI: 1.32-2.01, p<0.001) compared to
      reference (low ACR/no MetS). Similar associations were found for the high ACR/no
      MetS group. Low ACR/MetS was associated with myocardial infarction only (HR 1.82;
      95% CI: 1.39-2.37, p<0.001). MetS predicted neither stroke nor mortality.
      Adjusted for its individual components, MetS was not associated with any end
      point. CONCLUSIONS: ACR>or=0.75 mg/mmol was associated with cardiovascular
      morbidity and all-cause mortality independently of MetS. MetS was not associated
      with any end-point beyond what was predicted from its components. Thus, low-grade
      albuminuria, but not MetS, may be used for risk stratification in non-diabetic
      subjects.

PMID- 19091315
TI  - Increased levels of procoagulant tissue factor-bearing microparticles within the
      occluded coronary artery of patients with ST-segment elevation myocardial
      infarction: role of endothelial damage and leukocyte activation.
AB  - OBJECTIVE: During myocardial infarction, platelet activation and endothelial
      apoptosis are responsible for the release of procoagulant membrane-derived
      microparticles (MPs) in the bloodstream. Few data are available on the potential
      role played by MPs in coronary atherothrombosis. In the present study, we
      investigated the levels and cellular origins of MPs within the occluded coronary
      artery of patients with ST-segment elevation myocardial infarction (STEMI)
      treated by primary angioplasty (PCI). METHODS: A total of 12 patients with STEMI
      treated by primary PCI within 24h of symptom onset were included in this study.
      MPs procoagulant activity and cellular origin were characterized within the
      occluded coronary artery before PCI (C(0)), after restoration of the epicardial
      blood flow (C(1)), and in blood collected from the femoral artery (F). RESULTS:
      Levels of leukocyte-derived CD11a(+) MPs, endothelial-derived CD105(+) MPs, and
      tissue factor (TF)-bearing MPs were significantly higher within the occluded
      coronary artery than in peripheral blood samples. Restoration of the epicardial
      blood flow led to a significant reduction of procoagulant CD11a(+) and CD105(+)
      MPs by 30% and 42%, respectively (p<0.05). CONCLUSIONS: Elevation of procoagulant
      MPs within the occluded coronary artery of patients with STEMI suggests their
      pathophysiological role in coronary atherothrombosis.

PMID- 19091316
TI  - Analyzing of high-density lipoprotein subfractions and low-density lipoprotein
      subfractions in human serum with anion-exchange chromatography.
AB  - OBJECTIVE: We previously established a separation method for five lipoprotein
      classes (HDL, LDL, IDL, VLDL and chylomicrons) in human serum by using anion
      exchange high-performance liquid chromatography (AEX-HPLC). It was thought that
      analyzing of the subfractions of HDL or LDL is important for study of the
      atherogenic lipoproteins in atherosclerotic diseases, because a large number of
      studies were reported regarding them. Therefore, we estimated a separation mode
      of AEX-HPLC for analyzing cholesterol levels of two HDL-subfractions and two LDL
      subfractions. METHODS: In this method, the lipoproteins were separated by a step
      gradient of sodium perchlorate concentration, and the separated lipoproteins were
      detected by using a post-column reactor with a reagent containing cholesterol
      esterase and cholesterol oxidase. RESULTS: The major component of earlier-eluting
      fraction in HDL (HDL-f) and later-eluting fraction in HDL (HDL-s) were HDL3 and
      HDL2, respectively. The retention time of peak of earlier-eluting fraction in LDL
      (LDL-f) was changed into that of later-eluting fraction in LDL (LDL-s) by the
      oxidization, incubating 2 micromol/l copper ion in PBS for 3h at 37 degrees C.
      The within- and between-day assay coefficients of variation (CV) for cholesterol
      levels of the lipoprotein subfractions were in the ranges of 0.85-19.23% and 2.55
      23.50%, respectively. The cholesterol levels of HDL-f and HDL-s were lower in
      patients with coronary heart disease (CHD) than in healthy controls, while LDL-s
      cholesterol levels were higher in CAD patients than in healthy controls.
      CONCLUSIONS: This accurate and convenient assay of the lipoprotein subfractions
      may be useful for studying the atherogenic lipoproteins.

PMID- 19091318
TI  - Recent advances in gas chromatography for solid and liquid stationary phases
      containing metal ions.
AB  - This review is devoted to the application of metal complexes as column packings
      and liquid stationary phases in gas chromatography. Particular attention is paid
      to the stationary phases with nitrogen-containing functional groups (e.g., amine
      and ketoimine) and beta-diketonates on the modified silica surface. The review
      also concerns the results of the research on metallomesogenes and chiral
      stationary phases. The factors influencing the retention mechanism in
      complexation gas chromatography are discussed. Practical application of the metal
      chelate-containing chromatographic packings for analytical separation of organic
      substances is considered.

PMID- 19091317
TI  - 25-Hydroxyvitamin D deficiency is independently associated with cardiovascular
      disease in the Third National Health and Nutrition Examination Survey.
AB  - OBJECTIVE: Serum 25-hydroxyvitamin D [25(OH)D] levels are inversely associated
      with important cardiovascular disease (CVD) risk factors. However, the
      association between 25(OH)D levels and prevalent CVD has not been extensively
      examined in the general population. METHODS: We performed a cross-sectional
      analysis of data from the Third National Health and Nutrition Examination Survey
      (1988-1994) and examined the association between serum 25(OH)D levels and
      prevalence of CVD in a representative population-based sample of 16,603 men and
      women aged 18 years or older. Prevalence of CVD was defined as a composite
      measure inclusive of self-reported angina, myocardial infarction or stroke.
      RESULTS: In the whole population, there were 1308 (8%) subjects with self
      reported CVD. Participants with CVD had a greater frequency of 25(OH)D deficiency
      [defined as serum 25(OH)D levels <20 ng/mL] than those without (29.3% vs. 21.4%;
      p<0.0001). After adjustment for age, gender, race/ethnicity, season of
      measurement, physical activity, body mass index, smoking status, hypertension,
      diabetes, elevated low-density lipoprotein cholesterol, hypertriglyceridemia, low
      high-density lipoprotein cholesterol, chronic kidney disease and vitamin D use,
      participants with 25(OH)D deficiency had an increased risk of prevalent CVD (odds
      ratio 1.20 [95% confidence interval (CI) 1.01-1.36; p=0.03]). CONCLUSIONS: These
      results indicate a strong and independent relationship of 25(OH)D deficiency with
      prevalent CVD in a large sample representative of the US adult population.

PMID- 19091319
TI  - Packing density, permeability, and separation efficiency of packed microchips at
      different particle-aspect ratios.
AB  - HPLC microchips are investigated experimentally with respect to packing density,
      pressure drop-flow rate relation, hydraulic permeability, and separation
      efficiency. The prototype microchips provide minimal dead volume, on-chip UV
      detection, and a 75 mm long separation channel with a ca. 50 microm x 75 microm
      trapezoidal cross-section. A custom-built stainless-steel holder allowed to adopt
      optimized packing conditions. Separation channels were slurry-packed with 3, 5,
      and 10 microm-sized spherical, porous C8-silica particles. Differences in
      interparticle porosity, permeability, and plate height data are analyzed and
      consistently explained by different microchannel-to-particle size (particle
      aspect) ratios and particle size distributions.

PMID- 19091320
TI  - Analysis of potassium formate in airport storm water runoff by headspace solid
      phase microextraction and gas chromatography-mass spectrometry.
AB  - Potassium formate was extracted from airport storm water runoff by headspace
      solid-phase microextraction (HS-SPME) and analyzed by GC-MS. Formate was
      transformed to formic acid by adding phosphoric acid. Subsequently, formic acid
      was derivatized to methyl formate by adding methanol. Using sodium [(2)H]formate
      (formate-d) as an internal standard, the relative standard deviation of the peak
      area ratio of formate (m/z 60) and formate-d (m/z 61) was 0.6% at a concentration
      of 208.5 mg L(-1). Calibration was linear in the range of 0.5-208.5 mg L(-1). The
      detection limit calculated considering the blank value was 0.176 mg L(-1). The
      mean concentration of potassium formate in airport storm water runoff collected
      after surface de-icing operations was 86.9 mg L(-1) (n=11) with concentrations
      ranging from 15.1 mg L(-1) to 228.6 mg L(-1).

PMID- 19091321
TI  - Simple and precise detection of lipid compounds present within liposomal
      formulations using a charged aerosol detector.
AB  - In recent decades the use of liposomal preparations as drug delivery systems has
      become very attractive in pharmaceutical development. Therefore, thorough
      characterization and quantification of the lipids which form liposomes is wished
      from both investigators and regulatory authorities when the application in humans
      is being considered. In this study a new HPLC method for the detection of lipids
      in liposomal formulations was established using corona charged aerosol detection
      (CAD) which has the advantage to be independent of the chemical properties of the
      analytes. The superiority of this method over UV detection was demonstrated.
      Compared to UV detection no absorption effects of the organic solvent in the
      mobile phase interfering with the lipid signals were observed with CAD. CAD
      showed good linearity (R(2)>0.990) for all liposomal compounds. The acceptance
      criteria for precision including repeatability were met. The average recovery for
      each of the excipients of the liposomal formulation was in the range of 90.0
      110%.

PMID- 19091322
TI  - Application of response surface method for optimization of dispersive liquid
      liquid microextraction of water-soluble components of Rosa damascena Mill.
      essential oil.
AB  - Dispersive liquid-liquid microextraction (DLLME) coupled with gas chromatography
      mass spectrometry (GC-MS) was applied for the determination of Rose water
      constituents. The effective parameters such as volume of extraction and disperser
      solvents, temperature, and salt effect were inspected by a full factorial design
      to identify important parameters and their interactions. It showed that salt
      addition had no effect on the efficiency. Next, a central composite design was
      applied to obtain optimum point of the important parameters. The optimal
      condition was obtained as 37.0 microL for extractor, 0.42 mL for disperser and
      temperature for 48 degrees C. The main components that were extracted at the
      optimum point were benzeneethanol (24.87%), geraniol (23.07%), beta-citronellol
      (22.38%), nerol (8.48%), eugenol (5.98%) and linalool (5.62%).

PMID- 19091323
TI  - Sense and nonsense of high-temperature liquid chromatography.
AB  - High-temperature liquid chromatography (HTLC) is recognized today as a valuable
      technique in reversed-phase high-performance liquid chromatography (RP-HPLC).
      Column temperature can play a role in reducing analysis time, modifying
      retention, controlling selectivity, changing efficiency or improving detection
      sensitivity. The different effects of high temperatures on reversed-phase
      separations, the practical limitations due to the instrumentation, the limits and
      the main advantages of HTLC, especially for the separation of polar and ionized
      compounds, are reviewed.

PMID- 19091324
TI  - Central primitive neuroectodermal tumour with ependymal differentiation in a dog.
AB  - A central primitive neuroectodermal tumour (PNET) with ependymal differentiation
      was identified in an 18-month-old female Australian terrier dog that died
      following signs of central nervous system disease. A large space-occupying
      haemorrhagic mass replaced the thalamus and part of the hypothalamus of the
      brain. Microscopical examination revealed a tumour formed by a compact sheet of
      small cells that contained ependymal and perivascular pseudorosettes.
      Immunohistochemically, the neoplastic cells variably expressed glial fibrillary
      acidic protein, neuron-specific enolase, vimentin and cytokeratin, consistent
      with divergent differentiation of the tumour. This case is thought to represent
      the first description of PNET with ependymal differentiation in a dog.

PMID- 19091325
TI  - Expression of steroid receptors and calponin in a cervical leiomyoma in a young
      pig.
AB  - Thickening of the uterine cervix and bilateral ovarian cystic change was
      identified in a 6-month-old pig during routine abattoir inspection.
      Microscopically, the cervical lesion comprised a non-encapsulated mass of densely
      packed, large and monomorphic spindle cells within the myometrium.
      Immunohistochemically, the majority of these neoplastic cells expressed the
      cytoplasmic terminal smooth muscle differentiation marker calponin, the nuclear
      oestrogen receptor alpha and the progesterone receptor. The ovarian cysts were
      classified as follicular cysts. A diagnosis of leiomyoma of the uterine cervix
      with bilateral ovarian follicular cysts was made. The expression of calponin as a
      marker of smooth muscle differentiation in tumours of the genital tract of the
      pig has not previously been reported. The expression of steroid hormone receptors
      suggests a role for steroid hormones derived from the ovarian follicular cysts in
      tumourigenesis.

PMID- 19091326
TI  - An immunohistochemical analysis of canine haemangioma and haemangiosarcoma.
AB  - The aim of the present study was to investigate immunohistochemically aspects of
      the biology of canine endothelial neoplasia. Forty samples of canine cutaneous
      and visceral haemangiosarcoma (HSA), 29 samples of cutaneous and visceral
      haemangioma (HA) and 10 control samples of granulation tissue (GT) were labelled
      with antisera specific for vimentin, smooth muscle actin, von Willebrand factor
      (vWF), CD117 (KIT), vascular endothelial growth factor receptor-3 (VEGFR-3),
      vascular endothelial growth factor-C (VEGFC) and CD44. Further antisera were
      employed to determine the level of cellular proliferation (MIB-1 index) and
      toluidine blue staining was used to detect populations of tumour-infiltrating
      mast cells (MCs). There was greater expression of CD117, VEGFR-3 and CD44 in HSA
      than in HA, suggesting that these proteins might be suitable targets for the
      future development of novel therapeutic approaches to canine HSA. Marked
      infiltration of MC was detected in HA, suggesting a possible role for these cells
      in the pathogenesis of benign vascular neoplasia in the dog.

PMID- 19091327
TI  - Predictors of time-based prospective memory in children.
AB  - This study identified age differences in time-based prospective memory
      performance in school-aged children and explored possible cognitive correlates of
      age-related performance. A total of 56 7- to 12-year-olds performed a prospective
      memory task in which prospective memory accuracy, ongoing task performance, and
      time monitoring were assessed. Additional tests of time estimation, working
      memory, task switching, and planning were performed. Results showed a robust
      relationship between age and prospective memory performance even after
      controlling for ongoing task performance. Developmental differences in time
      monitoring were also observed, with older children generally adopting a more
      strategic monitoring strategy than younger children. The majority of age-related
      variance in prospective memory task performance could be explained by cognitive
      resources, in particular planning and task switching. In contrast, no further
      independent contribution of time estimation was observed. Findings are in line
      with the development of strategic behavior, as well as executive functioning, in
      school-aged children.

PMID- 19091328
TI  - The role of trauma-related distractors on neural systems for working memory and
      emotion processing in posttraumatic stress disorder.
AB  - The relevance of emotional stimuli to threat and survival confers a privileged
      role in their processing. In PTSD, the ability of trauma-related information to
      divert attention is especially pronounced. Information unrelated to the trauma
      may also be highly distracting when it shares perceptual features with trauma
      material. Our goal was to study how trauma-related environmental cues modulate
      working memory networks in PTSD. We examined neural activity in participants
      performing a visual working memory task while distracted by task-irrelevant
      trauma and non-trauma material. Recent post-9/11 veterans were divided into a
      PTSD group (n=22) and a trauma-exposed control group (n=20) based on the Davidson
      trauma scale. Using fMRI, we measured hemodynamic change in response to emotional
      (trauma-related) and neutral distraction presented during the active maintenance
      period of a delayed-response working memory task. The goal was to examine
      differences in functional networks associated with working memory (dorsolateral
      prefrontal cortex and lateral parietal cortex) and emotion processing (amygdala,
      ventrolateral prefrontal cortex, and fusiform gyrus). The PTSD group showed
      markedly different neural activity compared to the trauma-exposed control group
      in response to task-irrelevant visual distractors. Enhanced activity in ventral
      emotion processing regions was associated with trauma distractors in the PTSD
      group, whereas activity in brain regions associated with working memory and
      attention regions was disrupted by distractor stimuli independent of trauma
      content. Neural evidence for the impact of distraction on working memory is
      consistent with PTSD symptoms of hypervigilance and general distractibility
      during goal-directed cognitive processing.

PMID- 19091329
TI  - Progressive carotid artery stenosis with a novel tRNA phenylalanine mitochondrial
      DNA mutation.
AB  - Mitochondrial myopathy, encephalopathy, lactic acidosis and stroke-like episodes
      (MELAS) is a distinct clinical syndrome caused by mutations in the mitochondrial
      DNA. The pathogenesis of stroke-like episodes remains unknown but major vessels
      stenosis is not a cause of stroke-like episodes. We describe a novel
      heteroplasmic G617A transition in the mitochondrial transfer RNA phenylalanine
      gene in a patient with encephalomyopathy who presented with recurrent embolic
      ischemic strokes accompanied by transient occlusion of middle cerebral, anterior
      cerebral and internal carotid arteries. These ischemic strokes were presumed to
      be artery-to artery embolisms associated with carotid artery stenosis. Single
      muscle fiber analysis revealed the pathogenicity of the mutation although its
      causative role on carotid artery stenosis remains to be elucidated. This case
      expands phenotypic spectrum of mitochondrial disorders in terms of
      macroangiopathy, but macroangiopathy-related ischemic strokes should be
      distinguished from classic stroke-like episodes of MELAS that are speculated to
      be microangioapthy-related or non-ischemic neurovascular events.

PMID- 19091330
TI  - Derivation and validation of diagnostic criteria for chronic inflammatory
      demyelinating polyneuropathy.
AB  - To develop diagnostic criteria for chronic inflammatory demyelinating
      polyneuropathy (CIDP), a retrospective series of patients' records diagnosed by
      sexpert consensus as CIDP or other chronic polyneuropathies were analyzed.
      Classification and regression tree analysis was applied to 150 patients to derive
      a classification rule. According to the rule, diagnosis of CIDP required that a
      patient have a chronic non-genetic polyneuropathy, progressive for at least eight
      weeks, without a serum paraprotein and either 1) recordable compound muscle
      action potentials in > or =75% of motor nerves and either abnormal distal latency
      in >50% of nerves or abnormal motor conduction velocity in >50% of nerves or
      abnormal F wave latency in >50% of nerves; or 2) symmetrical onset of motor
      symptoms, symmetrical weakness of four limbs, and proximal weakness in > or =1
      limb. When validated in 117 patients, the rule had 83% sensitivity (95%
      confidence interval 69%-93%) and 97% specificity (95% confidence interval 89%
      99%) and performed better than published criteria.

PMID- 19091331
TI  - Efficacy of selenium and/or N-acetyl-cysteine for improving semen parameters in
      infertile men: a double-blind, placebo controlled, randomized study.
AB  - PURPOSE: We explored the efficacy of selenium and/or or N-acetyl-cysteine for
      improving semen parameters in infertile men, and the associations among semen
      quality and the concentrations of selenium and N-acetyl-cysteine in seminal
      plasma. MATERIALS AND METHODS: The study included 468 infertile men with
      idiopathic oligo-asthenoteratospermia who were randomized to receive 200 microg
      selenium orally daily (selenium group of 116), 600 mg N-acetyl-cysteine orally
      daily (N-acetyl-cysteine group of 118), 200 microg selenium plus 600 mg N-acetyl
      cysteine orally daily (selenium plus N-acetyl-cysteine group of 116) or similar
      regimen of placebo (control group of 118) for 26 weeks, followed by a 30-week
      treatment-free period. These patients provided blood samples for the measurement
      of serum testosterone, estradiol, follicle-stimulating hormone, luteinizing
      hormone, prolactin, inhibin B, selenium and N-acetyl-cysteine. Semen samples were
      also obtained for routine semen analysis, and the measurement of seminal plasma
      selenium and N-acetyl-cysteine. RESULTS: In response to selenium and N-acetyl
      cysteine treatment serum follicle-stimulating hormone decreased but serum
      testosterone and inhibin B increased. All semen parameters significantly improved
      with selenium and N-acetyl-cysteine treatment. Administering selenium plus N
      acetyl-cysteine resulted in additive beneficial effects. A significant positive
      correlation existed between the seminal plasma concentrations of selenium and N
      acetyl-cysteine, and semen parameters. A strong correlation was observed between
      the sum of the selenium and N-acetyl-cysteine concentrations, and mean sperm
      concentration (r = 0.67, p = 0.01), sperm motility (r = 0.64, p = 0.01) and
      percent normal morphology (r = 0.66, p = 0.01). CONCLUSIONS: These results
      indicate that supplemental selenium and N-acetyl-cysteine improve semen quality.
      We advocate their use for male infertility treatment.

PMID- 19091333
TI  - Perceptions and competence in evidence-based medicine: a survey of the American
      Urological Association Membership.
AB  - PURPOSE: We investigated the attitudes and opinions of urologists toward evidence
      based medicine to help guide future efforts of the American Urological
      Association and other organizations vested in the education and training of
      urologists. MATERIALS AND METHODS: From August to November 2006 we performed a
      mail survey of a random sample of 2,000 members of the American Urological
      Association. Questions in the survey addressed the role of evidence-based
      medicine in urology, participants' self-assessed understanding of evidence-based
      medicine related terminology, their familiarity with and use of web based
      evidence-based medicine resources, as well as their evidence-based medicine
      competence based on their understanding of core concepts such as randomization
      and blinding. RESULTS: A total of 889 respondents completed the survey resulting
      in a response rate of 45%. There was widespread agreement that practicing
      evidence-based medicine improves patient care (median score 8; IQR 7, 10) and
      that every urologist should be familiar with critical appraisal techniques
      (median score 9; IQR 8, 10). The percentage of respondents who indicated that
      they "understand and could explain to others" the terms number needed to treat,
      power and level of evidence was 42%, 29% and 18%, respectively. The American
      Urological Association Guidelines were used regularly by 35% and on occasion by
      51% of respondents. Of the participants 44% were unaware of the PubMed(R) search
      engine and only 14% used it regularly, while 76% were unaware of the Cochrane
      Database of Systematic Reviews and only 8% had ever used it. The mean evidence
      based medicine competence score for all respondents was 67.2% +/- 17.0%.
      CONCLUSIONS: The findings of this survey confirm that urologists have a favorable
      attitude toward evidence-based medicine. However, understanding of evidence-based
      medicine terminology, concepts and use of related resources among American
      Urological Association members leaves room for improvement. Increased efforts to
      promote an understanding of evidence-based medicine through workshops,
      publications and web based resources specifically for a urological audience
      appear indicated.

PMID- 19091334
TI  - Geographic distribution of urologists throughout the United States using a county
      level approach.
AB  - PURPOSE: The adequacy of the urologist work force in absolute numbers and
      relative distribution is unclear. To develop effective policies addressing the
      needs of an aging population we must better understand the urologist work force.
      We assessed the geographic distribution of urologists throughout the United
      States at the county level and determined the county characteristics associated
      with increased urologist density. MATERIALS AND METHODS: County level data from
      the Department of Health and Human Services Area Resource File and the United
      States Census were analyzed in this ecological study. Logistic regression and
      ordinal logistic regression models were built to identify predictors of urologist
      density, defined as the number of urologists per 100,000 individuals. National
      patterns of urologist density were mapped graphically at the county level.
      RESULTS: Overall 63% of the counties in the United States lack a urologist. Based
      on multivariate models urologists were less likely to be found in nonmetropolitan
      counties (OR 0.57, 95% CI 0.46-0.72) and rural counties (OR 0.03, 95% CI 0.02
      0.06) than in metropolitan counties, which confirmed visually mapped models.
      Patterns of urologist density also appeared to be influenced by climate and
      county education levels rather than by traditional socioeconomic measures.
      Urologists younger than 45 years old were 3 times less likely to be located in
      nonmetropolitan and rural counties than their older counterparts. CONCLUSIONS:
      The uneven distribution of urologists throughout the United States is likely to
      worsen as younger physicians continue to cluster in urban areas. Governing bodies
      must consider this distribution in their calls for increasing the number of
      training positions.

PMID- 19091335
TI  - Association of urological symptoms and chronic illness in men and women:
      contributions of symptom severity and duration--results from the BACH Survey.
AB  - PURPOSE: We investigated the association between lower urinary tract symptoms and
      chronic illness, such as heart disease, diabetes, hypertension and depression, in
      men and women. In addition, we determined whether a dose-response relationship
      exists in the association between the severity and duration of urological
      symptoms and major chronic illnesses. MATERIALS AND METHODS: The Boston Area
      Community Health Survey used a multistage stratified design to recruit a random
      sample of 5,503 adults who were 30 to 79 years old. Urological symptoms in the
      American Urological Association symptom index were included in analysis. RESULTS:
      Statistically significant associations that were consistent by gender were
      observed between depression and all urological symptoms. Nocturia of any degree
      of severity or duration was associated with heart disease in men and with
      diabetes in women. In men a dose-response relationship was observed for the
      association of symptom severity and/or the duration of urinary intermittency and
      frequency with heart disease, and for the association of urinary urgency with
      diabetes. In women a history of heart disease was associated with a weak stream
      and straining, while a history of hypertension was associated with urgency and a
      weak stream. CONCLUSIONS: Results indicate a dose-response relationship in the
      association of the severity and duration of urological symptoms with major
      chronic illnesses. An association between urinary symptoms and depression was
      observed in men and women. In contrast, the association between lower urinary
      tract symptoms and heart disease, diabetes or hypertension varied by gender,
      suggesting different mechanisms of association in men and women.

PMID- 19091336
TI  - Toward image guided robotic surgery: system validation.
AB  - PURPOSE: Navigation for current robotic assisted surgical techniques is primarily
      accomplished through a stereo pair of laparoscopic camera images. These images
      provide standard optical visualization of the surface but provide no subsurface
      information. Image guidance methods allow the visualization of subsurface
      information to determine the current position in relationship to that of tracked
      tools. MATERIALS AND METHODS: A robotic image guided surgical system was designed
      and implemented based on our previous laboratory studies. A series of experiments
      using tissue mimicking phantoms with injected target lesions was performed. The
      surgeon was asked to resect "tumor" tissue with and without the augmentation of
      image guidance using the da Vinci robotic surgical system. Resections were
      performed and compared to an ideal resection based on the radius of the tumor
      measured from preoperative computerized tomography. A quantity called the
      resection ratio, that is the ratio of resected tissue compared to the ideal
      resection, was calculated for each of 13 trials and compared. RESULTS: The mean
      +/- SD resection ratio of procedures augmented with image guidance was smaller
      than that of procedures without image guidance (3.26 +/- 1.38 vs 9.01 +/- 1.81, p
      <0.01). Additionally, procedures using image guidance were shorter (average 8 vs
      13 minutes). CONCLUSIONS: It was demonstrated that there is a benefit from the
      augmentation of laparoscopic video with updated preoperative images.
      Incorporating our image guided system into the da Vinci robotic system improved
      overall tissue resection, as measured by our metric. Adding image guidance to the
      da Vinci robotic surgery system may result in the potential for improvements such
      as the decreased removal of benign tissue while maintaining an appropriate
      surgical margin.

PMID- 19091337
TI  - Managing the urethra at transvaginal pelvic organ prolapse repair: a urodynamic
      approach.
AB  - PURPOSE: We evaluated the protocol that we use to determine whether a mid
      urethral synthetic sling will be placed at transvaginal pelvic organ prolapse
      repair. MATERIALS AND METHODS: A total of 140 patients underwent transvaginal
      repair for stage 2 to 4 pelvic organ prolapse, of whom 105 were treated according
      to the protocol and had a minimum 3 months of followup or required earlier
      intervention. Urodynamics were performed without prolapse reduction. When stress
      urinary incontinence was not identified, a pessary was placed and the study was
      repeated. Patients were designated as having urodynamic, occult or no stress
      urinary incontinence. Patients with urodynamic or occult stress urinary
      incontinence underwent a simultaneous mid urethral synthetic sling procedure,
      while those without urodynamic or occult stress urinary incontinence did not.
      Charts were reviewed to determine whether further intervention was required for
      stress urinary incontinence or obstruction. RESULTS: The risk of intervention due
      to obstruction after receiving a mid urethral synthetic sling was 8.5%. The risk
      of intervention for stress urinary incontinence in patients with no clinical,
      urodynamic or occult stress urinary incontinence and no mid urethral synthetic
      sling was 8.3%. The risk of intervention for stress urinary incontinence in
      patients with clinical stress urinary incontinence but no urodynamic or occult
      stress urinary incontinence and no mid urethral sling was 30%. CONCLUSIONS: Using
      our urodynamic protocol to manage the urethra at transvaginal pelvic organ
      prolapse repair the risk of intervention due to obstruction is essentially equal
      to the risk of intervention due to stress urinary incontinence when no clinical,
      urodynamic or occult stress urinary incontinence was present and no mid urethral
      synthetic sling was placed. In patients who report clinical stress urinary
      incontinence preoperatively despite no urodynamic or occult stress urinary
      incontinence there is a much higher rate of further intervention for stress
      urinary incontinence.

PMID- 19091339
TI  - Does previous extracorporeal shock wave lithotripsy affect the performance and
      outcome of percutaneous nephrolithotomy?
AB  - PURPOSE: ESWL and percutaneous nephrolithotomy are the primary treatment
      modalities for kidney stones. Furthermore, percutaneous nephrolithotomy is first
      line treatment when ESWL fails. We assessed how previous ESWL affects the
      performance and outcome of percutaneous nephrolithotomy. MATERIALS AND METHODS: A
      total of 1,008 patients underwent percutaneous nephrolithotomy between 2002 and
      2007, of whom 230 (22.8%) had a recent history of failed ESWL. Patient
      characteristics, operative findings, success and complication rates in patients
      with and without a history of ESWL were analyzed and compared. RESULTS: In the
      post-ESWL group mean stone size was significantly lower and the mean +/- SD
      interval between the last ESWL session and percutaneous nephrolithotomy was 3.4
      +/- 2.1 months (range 1 to 12). Mean operative time and fluoroscopic screening
      time were similar in the 2 groups (p >0.05). However, mean operative time per
      cm(2) stone and fluoroscopic screening time per cm(2) stone were significantly
      prolonged in the post-ESWL group (p <0.05). At a mean followup of 5.6 +/- 1.2
      months (range 3 to 6) an overall success rate of 89% was achieved. Success and
      complication rates were comparable in the 2 groups. CONCLUSIONS: Although similar
      success and complication rates were achieved with percutaneous nephrolithotomy
      after failed ESWL, percutaneous nephrolithotomy is usually more difficult with
      prolonged operative time and fluoroscopic screening time per cm(2) stone due to
      the tissue effects of ESWL and scattered stone fragments in the pelvicaliceal
      system.

PMID- 19091340
TI  - Collagen injection for female urinary incontinence after urethral or periurethral
      surgery.
AB  - PURPOSE: We evaluated the result of periurethral collagen injection in
      incontinent patients after prior urethral surgery. MATERIALS AND METHODS: We
      reviewed the charts of patients who underwent periurethral collagen injection
      between January 2000 and December 2006 for persistent stress urinary incontinence
      after a failed suspension procedure or urethral repair. Preoperative assessment
      included the validated Urogenital Distress Inventory-6 symptom questionnaire, a
      single global quality of life score, history and physical examination, cystogram
      while standing and multichannel urodynamics. All patients had a well supported
      urethra and intrinsic sphincteric deficiency. Outcome measures included
      questionnaires and 3-dimensional urethral ultrasound at 6 weeks, 6 to 12 months
      and yearly thereafter. In patients who were still symptomatic after the first
      injection a repeat injection was considered when there was asymmetrical or low
      collagen volume on ultrasound, and another therapy was considered when ultrasound
      findings were adequate. RESULTS: In 31 consecutive patients Urogenital Distress
      Inventory-6 question 3 and quality of life scores decreased after collagen
      injection (mean volume 5.5 cc). Baseline postoperative collagen volume on
      ultrasound was 2.6 cc (range 0.8 of 4.8). Of the patients 93% considered
      themselves clinically improved or cured, 17 of 31 required only 1 injection with
      a symmetrical configuration in 83%, while 8 received 1 or 2 more injections
      because of an asymmetrical configuration (75%) and/or low volume. Despite a mean
      collagen volume of 3.2 cc (range 2 to 4.3) 6 women with persistent stress urinary
      incontinence underwent a pubovaginal sling procedure. Eight of 25 patients
      requiring only collagen had stable collagen volume for 2 years without repeat
      injection. CONCLUSIONS: Collagen injection is a viable option with satisfactory
      results in this complex population.

PMID- 19091341
TI  - Long-term outcomes of external sphincterotomy in a spinal injured population.
AB  - PURPOSE: External sphincterotomy is an accepted option for treating patients with
      detrusor-sphincter dyssynergia. However, long-term outcome data are limited. We
      ascertained the outcome of treatment results for this procedure. MATERIALS AND
      METHODS: A database was reviewed for patients undergoing external sphincterotomy
      at a large tertiary referral spinal injuries center. RESULTS: For 84 primary
      sphincterotomies the mean duration of successful outcome was 81 months. A second
      procedure was required in 30 patients and mean duration of success thereafter was
      80 months. Recurrent symptomatic episodes of urinary tract infection, recurrent
      detrusor-sphincter dyssynergia or upper tract dilatation eventually ensued in 57
      of 84 patients (68%). Renal failure did not develop in any patients. CONCLUSIONS:
      External sphincterotomy protects the upper renal tracts and provides extended
      periods of satisfactory bladder emptying. However, it may require ongoing
      revision and should potentially be regarded as a staged intervention.

PMID- 19091342
TI  - Staged reconstruction of long segment urethral strictures in men with previous
      pediatric hypospadias repair.
AB  - PURPOSE: Reconstruction of long segment urethral stricture disease in adults with
      a history of pediatric hypospadias repair remains complex secondary to poor
      urethral blood supply, extensive penile scarring and the need for significant
      amounts of graft or flap tissue. We describe our experience with staged
      urethroplasty in this cohort of men. MATERIALS AND METHODS: A total of 15 males
      underwent staged urethroplasty for urethral stricture disease following previous
      hypospadias repair in childhood. All men underwent 2-stage repair with a minimum
      of 6 months separating each operation. Bulbar urethral stricture disease due to
      previous dilation was seen in 2 of the 15 men (14%). Graft sources included
      buccal mucosa in 12 cases, full-thickness hairless abdominal wall skin in 2,
      penile skin in 1 and posterior auricular tissue in 1. RESULTS: Median patient
      followup was 22 months (range 5 to 62) after stage 2 closure. Median patient age
      at presentation was 31 years (range 19 to 57). Mean stricture length was 8 cm
      (range 5 to 14) and mean graft area was 22 cm(2) (range 10 to 38). There was no
      clinical evidence of stricture recurrence, fistula or wound dehiscence at last
      followup in 13 of the 15 men (86%). Two men with a congenital hypoplastic glans
      were left with distal hypospadias. Minor voiding symptoms were described in 3 of
      the 15 men (21%) with resolution in all by 6 months postoperatively. CONCLUSIONS:
      We describe outcomes after staged reconstruction for extensive urethral stricture
      disease in men after previous pediatric hypospadias repair in childhood. At
      intermediate followup staged urethroplasty provided acceptable outcomes.

PMID- 19091343
TI  - Pretreatment semen parameters in men with cancer.
AB  - PURPOSE: Whether the presence or specific type of cancer significantly affects
      semen quality is controversial. We evaluated the semen parameters and associated
      malignancies of men with cancer who cryopreserved sperm at our institution before
      undergoing therapy. MATERIALS AND METHODS: We reviewed the database from our
      cryopreservation laboratory during a 5-year period. Office charts of 409 of 1,409
      patients were available for review. Age at banking, semen volume, sperm density,
      percent motile sperm and type of cancer were recorded. Semen parameters were
      compared to values for fertile and subfertile men established by the National
      Cooperative Reproductive Medicine Network as well as from a large local pre
      vasectomy cohort to consider geographic variations. RESULTS: A total of 717 semen
      samples from 409 men included 45% with testicular cancer, 10% with Hodgkin's
      lymphoma, 7% with nonHodgkin's lymphoma, 6% with sarcoma, 6% with prostate
      cancer, 5% with leukemia, 3% with gastrointestinal cancer and 2% with central
      nervous system tumors. Of these men 16% had unspecified or other rare
      malignancies. Mean patient age was 29.9 years (range 11.9 to 87.7), mean semen
      volume was 2.8 ml (range 0.1 to 15.0), mean sperm density was 47.4 x 10(6)/ml
      (range 0.1 to 320) and mean sperm motility was 50.0% (range 1% to 90%). For men
      with testicular cancer sperm density and motility were in the intermediate range.
      Parameters for men with all other malignancies were in the fertile range for
      density and intermediate range for motility. CONCLUSIONS: Men with most types of
      cancer have pretreatment semen parameters in the fertile range for density and in
      the intermediate range for motility. However, men with testicular cancer
      statistically have lower semen quality compared to those with other malignancies.
      These findings further highlight the importance of pretreatment fertility
      preservation in this patient population before undergoing gonadotoxic treatments.

PMID- 19091344
TI  - Estimating the risk of cancer associated with imaging related radiation during
      surveillance for stage I testicular cancer using computerized tomography.
AB  - PURPOSE: Computerized tomography has a critical role in the surveillance of stage
      I nonseminomatous germ cell tumors of the testis. Some protocols call for up to
      16 computerized tomography scans over 5 years, thereby exposing young patients to
      a significant amount of radiation. We estimated the lifetime risk of cancer
      incidence and cancer death from imaging related radiation received during
      surveillance of stage I nonseminomatous germ cell tumor. MATERIALS AND METHODS:
      Using a model with a 64-slice computerized tomography scanner obtaining images of
      the abdomen and pelvis with or without chest in a standardized, phantom male
      patient, organ specific radiation doses were estimated using Monte Carlo
      simulation techniques. Lifetime attributable risks of cancer were estimated using
      the approach outlined in the Biological Effects of Ionizing Radiation VII Phase 2
      report. RESULTS: With a 5-year surveillance protocol as suggested by the National
      Comprehensive Cancer Network, lifetime cancer risk ranged from 1 in 52 (1.9%) for
      an 18-year-old to 1 in 63 for a 40-year-old patient (1.2%). If chest computerized
      tomography is also performed the risk increases to 1 in 39 (2.6%) and 1 in 85
      (1.6%), respectively. Lung and colon cancer accounted for most of the risk. The
      relative risk of a secondary malignancy with surveillance compared to a single
      scan after retroperitoneal lymph node dissection is approximately 15.2.
      CONCLUSIONS: Computerized tomography used in testicular cancer surveillance
      protocols imparts large radiation doses and is associated with a significant risk
      of cancer. This risk should be factored into counseling patients with stage I
      nonseminomatous germ cell tumor.

PMID- 19091346
TI  - Effects of short-term finasteride on apoptotic factors and androgen receptors in
      prostate cancer cells.
AB  - PURPOSE: We explored the molecular correlates of the effect of finasteride on
      prostate tissue in patients undergoing radical prostatectomy. MATERIALS AND
      METHODS: Patients undergoing radical prostatectomy for localized prostate cancer
      were eligible for study. After providing informed consent patients were
      randomized to receive 5 mg finasteride or placebo daily for at least 30 days
      before surgery. At surgery prostate tissue was harvested from the surgical
      specimen and sent for analysis. Tissue samples were analyzed for the pro
      apoptotic factors caspase-3, caspase-7 and IGFBP-3. Samples were also analyzed
      for the tumor suppressor/proto-oncoproteins bcl-2, p53 and p21. Finally, tissues
      were analyzed for androgen receptor density and insulin growth factor-1. RESULTS:
      A total of 22 study and 20 placebo samples were collected and analyzed.
      Negligible staining for bcl-2 or caspase-3 was noted in each group. Statistical
      differences were not observed for bcl-2, p53, p21 or insulin growth factor-1
      between the groups. There was a statistically significant difference in caspase-7
      and IGFBP-3. A mean of 77% and 99.9% of cells stained for caspase-7 in the
      treatment and placebo groups, respectively (p = 0.007). In 3 patients caspase-7
      staining disappeared completely and it was decreased by 70% and 50% in 1 patient
      each. Mean intensity staining for IGFBP-3 was 1.03 in the treatment group and
      1.54 in the placebo group (p = 0.005). The staining intensity of nuclear androgen
      receptors on benign and cancerous cells was not significantly different between
      the treatment and placebo groups. However, there was a significant difference in
      androgen receptor staining between benign and cancer cells in the 2 populations.
      Mean nuclear androgen receptor staining intensity in all cancer and all benign
      tissue samples was 119.3 and 151.8, respectively (0.001). CONCLUSIONS:
      Finasteride administered 30 days before surgery appears to decrease the apoptotic
      factors caspase-7 and IGFBP-3 in cancer cells, while having little to no effect
      on caspase-3, insulin growth factor-1, bcl-2, p53 and p21. This short-term study
      may have interesting implications for interpreting Prostate Cancer Prevention
      Trial data on the molecular level. No differences were noted between the
      treatment and placebo groups in the expression of nuclear androgen receptor.
      However, decreased expression of androgen receptors was present in cancer cells
      compared to that in benign prostate cells in the 2 groups.

PMID- 19091347
TI  - Phase II study of Dutasteride for recurrent prostate cancer during androgen
      deprivation therapy.
AB  - PURPOSE: We determined the response rate to and safety of a dual 5alpha-reductase
      inhibitor, dutasteride, in men with castration recurrent prostate cancer.
      MATERIALS AND METHODS: A total of 28 men with asymptomatic castration recurrent
      prostate cancer were treated with 3.5 mg dutasteride daily (luteinizing hormone
      releasing hormone treatment continued), and evaluated monthly for response and
      toxicity. Eligibility included appropriate duration antiandrogen withdrawal,
      baseline prostate specific antigen 2.0 ng/ml or greater and a new lesion on bone
      scan, increase in measurable disease using Response Evaluation Criteria in Solid
      Tumors criteria, or 2 or more consecutive prostate specific antigen measurements
      increased over baseline. Outcomes were progression, stable disease, partial
      response (prostate specific antigen less than 50% of enrollment for 4 or more
      weeks) or complete response. RESULTS: There were 25 evaluable men with a mean age
      of 70 years (range 57 to 88), a mean prostate specific antigen of 61.9 ng/ml
      (range 5.0 to 488.9) and mean Gleason score 8 (range 6 to 10), 15 of whom had
      bone metastases. Eight men had 10 grade 3 or higher adverse events using National
      Cancer Institute Common Terminology Criteria, all of which were judged to be
      unrelated to treatment. Of the 25 men 14 had disease progression by 2 months, 9
      had stable (2.5, 3, 3, 4, 4, 5, 5, 8.5, 9 months) disease, 2 had a partial
      response and none had a complete response. Overall median time to progression was
      1.87 months (range 1 to 10, 95% CI 1.15-3.91). CONCLUSIONS: Dutasteride rarely
      produces biochemical responses in men with castration recurrent prostate cancer.
      However, further study is warranted given its favorable safety profile.

PMID- 19091348
TI  - Efficacy and survival associated with cystoscopy and clot evacuation for
      radiation or cyclophosphamide induced hemorrhagic cystitis.
AB  - PURPOSE: We assessed the outcome of patients with hemorrhagic cystitis severe
      enough to require cystoscopy and clot evacuation. MATERIALS AND METHODS: We
      retrospectively evaluated the records of 33 patients with cyclophosphamide or
      radiation induced hemorrhagic cystitis treated with cystoscopy. RESULTS: Mean
      followup of living patients was 76 months. Of 33 patients 20 (61%) had resolution
      of hematuria after single cystoscopy unrelated to hemorrhagic cystitis etiology.
      Only 4 of 11 patients (36%) had resolution after 2 or more cystoscopies, and all
      were in the radiation induced hemorrhagic cystitis group (4 of 6, 67%) with none
      in the cyclophosphamide induced hemorrhagic cystitis group (0 of 5, p = 0.02).
      Hematuria was refractory to cystoscopy in 9 patients and ileal conduits were
      created in 4. Kaplan-Meier overall survival at 1, 2 and 5 years was 58%, 51% and
      43%, respectively, with survival tending to be worse in patients who received
      cyclophosphamide for bone marrow transplantation induction. Of the 18 deaths 3
      were due to complications of hemorrhagic cystitis, 13 were due to the disease
      underlying the hemorrhagic cystitis and 2 were unrelated. CONCLUSIONS: The
      response of hemorrhagic cystitis to single cystoscopy and clot evacuation is
      reasonable but response to subsequent cystoscopy (unless the hemorrhagic cystitis
      is radiation induced) is less likely, so alternate interventions should be
      considered if hematuria does not resolve after initial cystoscopy. Patients with
      hemorrhagic cystitis requiring cystoscopy have a poor prognosis even if hematuria
      resolves, although most deaths are related to the disease underlying the
      hemorrhagic cystitis rather than its direct result.

PMID- 19091349
TI  - Changes in continence and erectile function between 2 and 4 years after radical
      prostatectomy.
AB  - PURPOSE: There is a paucity of information on changes in continence and erectile
      function beyond 2 years after radical prostatectomy. We prospectively examined
      changes in continence and erectile function between 2 and 4 years after radical
      prostatectomy. MATERIALS AND METHODS: Between October 2000 and August 2003, 731
      consecutive men underwent open retropubic radical prostatectomy for clinically
      localized prostate cancer. Preoperative and postoperative continence, and
      erectile function were ascertained using the UCLA Prostate Cancer Index. The 48
      month prospective self-assessment followup questionnaire captured changes in
      urinary control and erectile function between 24 and 48 months, including marked,
      moderate or slight improvement, no change or worsening. RESULTS: Overall between
      24 and 48 months after radical prostatectomy 23.4% and 42.3% of men showed any
      degree of improvement in continence and erectile function, and 12.2% and 19.8%
      showed marked and moderate improvement in continence and erectile function,
      respectively. The probability of experiencing any qualitative improvement in
      urinary continence was not significantly different in men who were continent or
      incontinent at 24 months. The likelihood of experiencing any qualitative
      improvement in erectile function was significantly greater in men who were potent
      at 24 months compared to those who were impotent. CONCLUSIONS: Our study provides
      compelling evidence that clinically significant improvements in urinary control
      and erectile function occur beyond 2 years after radical prostatectomy. These
      qualitative improvements are greatest for erectile function in men who were
      potent at 2 years. Therefore, men should not be counseled that maximal urinary
      continence or erectile function are achieved by 24 months after radical
      prostatectomy.

PMID- 19091351
TI  - Long-term impact of a robot assisted laparoscopic prostatectomy mini fellowship
      training program on postgraduate urological practice patterns.
AB  - PURPOSE: Robot assisted laparoscopic prostatectomy has stimulated a great deal of
      interest among urologists. We evaluated whether a mini fellowship for robot
      assisted laparoscopic prostatectomy would enable postgraduate urologists to
      incorporate this new procedure into clinical practice. MATERIALS AND METHODS:
      From July 2003 to July 2006, 47 urologists participated in the robot assisted
      laparoscopic prostatectomy mini fellowship program. The 5-day course had a 1:2
      faculty-to-attendee ratio. The curriculum included lectures, tutorials, surgical
      case observation, and inanimate, animate and cadaveric robotic skill training.
      Questionnaires assessing practice patterns 1, 2 and 3 years after the mini
      fellowship program were analyzed. RESULTS: One, 2 and 3 years after the program
      the response rate to the questionnaires was 89% (42 of 47 participants), 91% (32
      of 35) and 88% (21 of 24), respectively. The percent of participants performing
      robot assisted laparoscopic prostatectomy in years 1 to 3 after the mini
      fellowship was 78% (33 of 42), 78% (25 of 32) and 86% (18 of 21), respectively.
      Among the surgeons performing the procedure there was a progressive increase in
      the number of cases each year with increasing time since the mini fellowship
      training. In the 3 attendees not performing the procedure 3 years after the mini
      fellowship training the reasons were lack of a robot, other partners performing
      it and a feeling of insufficient training to incorporate the procedure into
      clinical practice in 1 each. One, 2 and 3 years following the mini fellowship
      training program 83%, 84% and 90% of partnered attendees were performing robot
      assisted laparoscopic prostatectomy, while only 67%, 56% and 78% of solo
      attendees, respectively, were performing it at the same followup years.
      CONCLUSIONS: An intensive, dedicated 5-day educational course focused on learning
      robot assisted laparoscopic prostatectomy enabled most participants to
      successfully incorporate and maintain this procedure in clinical practice in the
      short term and long term.

PMID- 19091352
TI  - Risk factors for lower urinary tract symptoms suggestive of benign prostatic
      hyperplasia in a community based population of healthy aging men: the Krimpen
      Study.
AB  - PURPOSE: We explored risk factors for lower urinary tract symptoms suggestive of
      benign prostatic hyperplasia in the open population. MATERIALS AND METHODS: A
      longitudinal, population based study with a followup of 6.5 years was done in
      1,688 men who were 50 to 78 years old. Data were collected on transrectal
      ultrasound of prostate volume, urinary flow rate, ultrasound estimated post-void
      residual urine volume, generic and disease specific quality of life, and symptom
      severity based on the International Prostate Symptom Score. Lower urinary tract
      symptoms suggestive of benign prostatic hyperplasia were defined as an
      International Prostate Symptom Score of greater than 7 after a report of a score
      of less than 7 in the previous round. A multivariate Cox proportional hazard
      model was constructed to determine risk factors for clinical benign prostatic
      hyperplasia after correcting for patient age. RESULTS: Total followup was 4,353
      person-years. During followup 180 events of attaining an International Prostate
      Symptoms Score of greater than 7 occurred. Multivariate analysis showed that
      functional bladder capacity, post-void residual urine volume, treatment for
      cardiac diseases, education level, antidepressant use, calcium antagonist use,
      erectile function or dysfunction, prostate specific antigen and a family history
      of prostate cancer were determinants with a significant HR. CONCLUSIONS: In
      addition to age, we established 9 significant determinants for lower urinary
      tract symptoms suggestive of benign prostatic hyperplasia. However, not all risk
      factors for lower urinary tract symptoms suggestive of benign prostatic
      hyperplasia are accounted for since we can conclude that 1 of 3 men without these
      risk factors will still be diagnosed with lower urinary tract symptoms suggestive
      of benign prostatic hyperplasia between ages 50 and 80 years.

PMID- 19091353
TI  - Simultaneous bilateral native nephrectomy and living donor renal transplantation
      are successful for polycystic kidney disease: the University of Maryland
      experience.
AB  - PURPOSE: Patients with autosomal dominant polycystic kidney disease have
      significant morbidity due to large kidney size and the resultant compression of
      adjacent organs. Surgical extirpation is limited to the most severe cases due to
      the risk of complications. Typically surgical extirpation of autosomal dominant
      polycystic kidney disease kidneys and renal transplantation are performed in
      staged fashion. The additive risks of these 2 procedures have been a barrier to a
      simultaneous surgical approach. The risks include transplant compromise due to
      cyst rupture, bleeding, adjacent organ injury and anti-HLA antibody sensitization
      from transfusion in cases of pretransplant nephrectomy. We reviewed the results
      of and graft survival data on bilateral nephrectomy for autosomal dominant
      polycystic kidney disease with simultaneous live donor renal transplantation.
      MATERIALS AND METHODS: From August 2003 to November 2007, 20 sets of kidneys were
      removed in patients with autosomal dominant polycystic kidney disease, followed
      by simultaneous live donor transplantation. We retrospectively reviewed the
      outcomes in terms of surgical time, complications, length of stay, transfusion
      rate and transplant kidney status. RESULTS: A total of 20 sets of kidneys were
      removed and these patients then underwent immediate live donor renal
      transplantation. Mean operative time was 190 minutes for the bilateral
      nephrectomy portion alone with an average estimated blood loss of 723 cc.
      Complications were rare and well tolerated. Mean hospital stay was 7.2 days for
      this procedure. Graft survival was 100% and all patients reported relief of
      symptoms. CONCLUSIONS: Bilateral nephrectomy and immediate transplantation in
      patients with autosomal dominant polycystic kidney disease can be done with
      minimal morbidity. Preliminary studies show that patients may have significant
      improvement in quality of life from this procedure and graft viability is not
      compromised.

PMID- 19091354
TI  - Cystic lesions of the prostate gland: an ultrasound classification with
      pathological correlation.
AB  - PURPOSE: Cysts of prostate tissue are common. Most cases are diagnosed accidently
      during ultrasound but they sometimes have clinical relevance when related to
      lower urinary tract symptoms, infertility or the expression of neoplastic
      disorders. Clinical relevance is linked to the differential diagnosis of the
      different types of cysts. We provide an updated classification of prostate cyst
      disorders and indicate how these disorders appear on transrectal ultrasound based
      on our experience and a literature review. MATERIALS AND METHODS: We
      retrospectively analyzed the ultrasound database and surgical specimen archives.
      We performed a MEDLINE(R) search of the peer reviewed literature on the diagnosis
      and classification of prostate cysts. RESULTS: Cysts of the prostate gland can be
      classified into 6 categories, including 1) isolated medial cysts, 2) cysts of the
      ejaculatory duct, 3) simple or multiple cysts of the parenchyma, 4) complicated
      infectious or hemorrhagic cysts, 5) cystic tumors and 6) cysts secondary to
      parasitic disease. Cysts of the prostate are related to atrophy of the prostate
      gland as well as to other well-known factors, such as inflammatory disease,
      benign prostatic hyperplasia, ejaculatory duct obstruction and cancer. The
      differential diagnosis and diagnostic criteria are shown for each category. A
      possible limitation of this classification is that the quantitative aspect of the
      cyst was not evaluated. This is the initial step toward a more detailed
      classification and the basis for further pathological studies. CONCLUSIONS: This
      comprehensive classification could be a useful tool in urological and
      andrological clinical practice, and for research purposes.

PMID- 19091356
TI  - Shallow sublittoral meiofauna communities and sediment polycyclic aromatic
      hydrocarbons (PAHs) content on the Galician coast (NW Spain), six months after
      the Prestige oil spill.
AB  - The aim of this work was to detect the impact of Prestige oil spill on
      meiobenthic community structure at higher levels of taxonomic aggregation. In
      addition, the relationship between sediment individual polycyclic aromatic
      hydrocarbon (PAH) concentration and meiofauna community structure was
      investigated. Six months after the Prestige oil spill, meiobenthos community and
      sediment PAHs content from seven shallow subtidal localities along the Galician
      coast were studied. Two sites presented differences in community structure,
      characterized by high densities of nematodes, gastrotrichs and turbellarians, and
      low densities of copepods. Chrysene and triphenylene were only found at these two
      disturbed sites and could be responsible for differences of meiobenthos community
      structure. However, differences in community structure of sites could be linked
      with sedimentary parameters, and discrimination between the effect of PAHs and
      sedimentary parameters was impossible due to the lack of baseline studies on
      meiobenthos and PAHs contents in this area.

PMID- 19091357
TI  - [Anterior lumbar interbody fusion for treatment of failed back surgery syndrome:
      a retrospective study of 46 cases].
AB  - BACKGROUND AND PURPOSE: Anterior lumbar interbody fusion (ALIF) has gained
      popularity for the treatment of degenerative disease of the lumbar spine. In this
      report, we present our experience with the ALIF procedure for treatment of failed
      back surgery syndrome following lumbar discectomy in a noncontrolled
      retrospective cohort. METHODS: From 1st January to 31 December 2005, we performed
      an ALIF in 46 patients presenting with low back pain with or without
      radiculopathy. All patients had a history of intractable pain resistant to
      conventional medical treatment and failed posterior lumbar surgery. Clinical and
      radiological outcomes were recorded. Neurological pain and functional outcomes
      were measured postoperatively (at 1, 3 and 12 months). Operative data,
      intraoperative complications, and the fusion rate were recorded. RESULTS: Forty
      six patients with a preoperative diagnosis of failed back surgery syndrome
      underwent ALIF. The mean follow-up was 21 months. Back pain and leg pain
      completely disappeared in 60.9% of patients, decreased but required occasional
      medication in 28.3%, and 10.8% declared no benefit from ALIF surgery. CONCLUSION:
      On the basis of our results, we found ALIF to be a safe and effective procedure
      for the treatment of failed back surgery syndrome.

PMID- 19091358
TI  - [Making the differential diagnosis between pituitary apoplexy and
      craniopharyngioma].
AB  - Pituitary apoplexy is characterized by an abrupt neurological deteriorating
      condition associated with rapid expansion of the pituitary gland, caused by
      ischemic necrosis and hemorrhage. Craniopharyngioma may be difficult to
      distinguish from pituitary apoplexy. In this study, we discuss a case of
      pituitary apoplexy in a 19-year-old male patient. In our patient, the tumor was
      confused with a craniopharyngioma because of the suprasellar extension of the
      tumor on magnetic resonance (MR) images and the hyperintensity in T1-weighted
      images, the young age of the patient, and the gradually progressive onset of the
      symptoms. In conclusion, even without a known history of pituitary adenoma or an
      abrupt onset of the clinical symptoms, the diagnosis of pituitary apoplexy should
      be considered in a patient with a suprasellar mass hyperintensity in T1-weighted
      MR images, which may mimic craniopharyngioma.

PMID- 19091359
TI  - Steroidal saponins from the roots of Trillium erectum (Beth root).
AB  - Eleven steroidal saponins including three previously unreported saponins 1-3, two
      known ecdysteroids and one fatty acid, have been isolated from the roots of
      Trillium erectum (Beth root) by RP-HPLC and characterized by spectroscopic (1D
      and 2D NMR experiments) and spectrometric (LCMS) methods.

PMID- 19091360
TI  - The power of detention in the management of non-compliance with tuberculosis
      treatment: a survey of Irish practitioners and analysis of potential legal
      liability.
AB  - OBJECTIVES: The detention of patients infected with tuberculosis has recently
      been the subject of significant professional and public interest. In Ireland, the
      power to detain and isolate probable sources of infectious disease is found in
      the Health Act 1947. The objective of this study was to describe the use of the
      power to detain, and to examine relevant legal implications. STUDY DESIGN: Cohort
      survey. METHODS: Respiratory and infectious disease physicians practising in the
      public sector were invited to complete a self-administered postal questionnaire.
      RESULTS: Of the 44 clinicians surveyed, 33 responded, representing a total of 356
      years of specialist practice (mean 10.8 years). Although 70% of respondents had
      made use of threats of formal detention in dealing with non-compliant patients,
      only one formal detention under statutory powers was identified. Infrastructural
      and legal concerns with the use of detention were common. There was widespread
      support for a broadening of the range of additional public health powers,
      including a power of prolonged detention in the setting of multi-drug-resistant
      tuberculosis. CONCLUSION: Detention and isolation of non-compliant tuberculosis
      patients remains in active use. Physicians detaining, or threatening to detain,
      patients continue to expose themselves to legal liability because of the outdated
      legal framework underlying those powers.

PMID- 19091361
TI  - Effect of the number of risk factors on betel quid chewing in adolescents living
      in rural Taiwan.

PMID- 19091362
TI  - Can primary care reduce inequalities in mental health?
AB  - OBJECTIVES: To explore the contributions that primary care could make to reducing
      and preventing inequalities in mental health through policy, local strategy and
      practice. STUDY DESIGN: The study used an interpretive policy analysis framework
      to investigate the ways in which inequalities in mental health and inequalities
      in health were interpreted by health and social policies, incorporated into a
      local strategic process in a primary care organization, and understood and acted
      upon by frontline primary care and mental health practitioners. The study
      involved analysis of nine health and social policy documents, observation of a
      mental health needs assessment process, and interviews with 21 frontline
      professionals from 14 different disciplines. METHODS: Data were collected using
      document analysis, observation, and interviews with frontline staff which
      included a vignette. Data were sorted using the Atlas-ti software programme, and
      a grounded theory approach guided the data collection and analysis. RESULTS:
      Policy documents demonstrated a disjointed picture of definitions and actions,
      and lacked a clear overall interpretation of inequalities in health or
      inequalities in mental health. The mental health needs assessment did not
      incorporate discussion about inequalities in mental health, despite some
      individual steering group members demonstrating concerns about inequalities in
      mental health. Frontline professionals defined inequalities as being linked to
      access to health services rather than social factors, and were often
      uncomfortable about discussing inequalities in mental health. A small minority
      suggested that they would explore or take action on the social circumstances of a
      patient presenting with potential mental health problems. CONCLUSIONS: The study
      found that policies were not driving practice for reducing inequalities in mental
      health within primary care, and the primary care organization studied was not
      conducive to addressing inequalities in mental health. However, some building
      blocks were in place at all levels that have the potential to be developed to
      enable primary care to address inequalities in mental health.

PMID- 19091363
TI  - Multidisciplinary research in public health: a case study of research on access
      to green space.
AB  - OBJECTIVES: Quantitative analysis of the physical and demographic parameters of
      access to Thames Chase Community Forest (TCCF), and how these have changed
      between 1990 and 2003; and qualitative exploration of our understanding of the
      links between health and the natural environment (TCCF), with a focus on the
      issue of 'access' to green space. STUDY DESIGN: Multimethod design involving both
      quantitative (analysis of physical access to green space) and qualitative
      (ethnography) components. METHODS: Quantitative analysis, using geographical
      information systems, of physical access to the community forest; and ethnographic
      research including participant observation, non-participant observation, in-depth
      interviews and attendance at meetings and conferences. RESULTS: The quantitative
      analysis showed that public access to green space improved between 1990 and 2003
      as a result of the regeneration and acquisition of new areas, and the average
      reduction in distance to green space was 162 m. However, such improvements were
      distributed differentially between population groups. In both 1990 and 2003,
      people from deprived areas and in poorer health had better access to green space
      than people from less deprived areas, but the greatest improvement in access to
      green space over this interval occurred in areas of below average deprivation
      (i.e. in the more affluent areas). The ethnographic research showed different
      interpretations of the notion of access. Use of TCCF was determined by a variety
      of factors including whether a person could 'imagine themselves' using such a
      space, different perceptions of what is actually being accessed (e.g. a place to
      exercise or a place to socialise), and ideas about using the countryside
      'properly'. CONCLUSIONS: The health benefits of using a green space, such as
      TCCF, for walking or exercising are well recognized. However, whether people
      choose to use local green space may be determined by a variety of factors. These
      are likely to include physical distance to access of green space, as well as
      perceptions and understandings of what is being accessed and how it should be
      used. This study has also illustrated the ways in which multiple methods can be
      integrated in public health research, and the merits of different approaches to
      undertaking multidisciplinary work of this type.

PMID- 19091364
TI  - Tuberculosis symptom screening among new prisoners in two Greater Manchester
      prisons.

PMID- 19091365
TI  - Comparison of effect of high intake of magnesium with high intake of phosphorus
      and potassium on urolithiasis in goats fed with cottonseed meal diet.
AB  - The effect of high intake of Mg on urolithiasis was compared with high intake of
      P and K in goats being fed with a cottonseed meal and rice straw diet. Eighteen
      wether goats were randomly allocated into group A, B and C evenly and fed with
      cottonseed meal and rice straw diet for three months. From day 60 onwards,
      KH(2)PO(4) and K(2)HPO(4) were provided via drinking water to goats in group B to
      increase the intake of P, K, and MgO to goats in group C to increase the intake
      of Mg. Blood and urine samples were collected to analyze the concentration of P,
      K, Mg and Ca, and the activity product (AP) of potassium magnesium phosphate
      (MKP) in urine was also calculated. The composition of calculi and urinary
      sedimentary crystals were examined by chemical qualitative analysis, X-ray
      diffraction, X-ray energy dispersive spectrometry and Fourier transform infrared
      spectroscopy. The results showed that the incidence of urolithiasis in group C
      (6/6) was higher than that in group A (1/6) and B (1/6) (P<0.05). The calculi
      were mainly composed of magnesium ammonium phosphate (MAP) and partly composed of
      MKP. MKP presented in crystals of different phases in this experiment. The high
      intake of Mg contributed to a significant increase of plasma Mg, but additional
      P, K did not cause a further increase of plasma P, K. Urine P, K, Mg and Ca and
      AP of MKP in group C decreased significantly after the onset of urolithiasis. In
      conclusion, high intake of Mg was more important in inducing struvite calculi
      compared with high intake of K and P in goats under these feeding conditions.
      Cottonseed meal and rice straw with additional Mg is a good dietary model for
      inducing struvite calculi in castrated goats.

PMID- 19091366
TI  - [Epilepsy and migraine, the crucial features of hallucinations].

PMID- 19091367
TI  - Inhibition of cellular alpha-glucosidases results in increased presentation of
      hepatitis B virus glycoprotein-derived peptides by MHC class I.
AB  - Inhibitors of alpha glucosidases prevent the trimming of oligosaccharides on
      certain nascent glycoproteins, including the hepatitis B virus MHBs envelope
      glycoprotein. MHBs proteins with untrimmed oligosaccharides do not interact with
      calnexin, increasing protein misfolding and subsequent degradation by
      proteasomes. As peptides loaded onto newly synthesized MHC class I complexes are
      predominantly derived from proteasomes, the possibility that glucosidase
      inhibition could increase presentation by MHC class I was determined. Using
      either a model epitope, or a natural MHBs epitope, it was demonstrated that
      glucosidase inhibitors enhanced presentation by MHC class I and promoted
      activation of antigen-specific CTLs, suggesting a pharmacologic approach to
      immune modulation.

PMID- 19091368
TI  - Replication of chicken anemia virus (CAV) requires apoptin and is complemented by
      VP3 of human torque teno virus (TTV).
AB  - To test requirement for apoptin in the replication of chicken anemia virus (CAV),
      an apoptin-knockout clone, pCAV/Ap(-), was constructed. DNA replication was
      completely abolished in cells transfected with replicative form of CAV/Ap(-). A
      reverse mutant competent in apoptin production regained the full level of DNA
      replication. DNA replication and virus-like particle (VLP) production of CAV/Ap(
      ) was fully complemented by supplementation of the wild-type apoptin. The virus
      yield of a point mutant, CAV/ApT(108)I, was 1/40 that of the wild type, even
      though its DNA replication level was full. The infectious titer of CAV was fully
      complemented by supplementing apoptin. Progeny virus was free from reverse
      mutation for T(108)I. To localize the domain within apoptin molecule inevitable
      for CAV replication, apoptin-mutant expressing plasmids, pAp1, pAp2, pAp3, and
      pAp4, were constructed by deleting amino acids 10-36, 31-59, 59-88 and 80-112,
      respectively. While Ap1 and Ap2 were preferentially localized in nuclei, Ap3 and
      Ap4 were mainly present in cytoplasm. Although complementation capacity of Ap3
      and Ap4 was 1/10 of the wild type, neither of them completely lost its activity.
      VP3 of TTV did fully complement the DNA replication and VLP of CAV/Ap(-). These
      data suggest that apoptin is inevitable not only for DNA replication but also VLP
      of CAV. The common feature of apoptin and TTV-VP3 presented another evidence for
      close relatedness of CAV and TTV.

PMID- 19091369
TI  - Mapping of determinants involved in the stimulation of HIV-1 expression by Sam68.
AB  - Control of HIV-1 RNA processing is central to the replication of the virus.
      Previously, we demonstrated that the cellular protein Sam68 enhances HIV-1
      structural protein expression and RNA 3' end processing. In this report, we show
      that Sam68 interacts with unspliced HIV-1 RNA and that other members of the
      STAR/GSG protein family also promote viral RNA 3' end processing. We define a
      portion of the GSG domain (Sam 97-255) as sufficient for enhancement of Rev
      dependent expression. In contrast to Sam68, Sam 97-255 increases unspliced RNA
      processing only in the presence of Rev in 293T cells. In a different cell line,
      Sam 97-255 enhances HIV-1 gene expression without enhancing RNA 3' end
      processing, suggesting that stimulation of 3' end processing is not required for
      enhancement of HIV-1 gene expression. Overall, these results indicate that Sam68
      and the mutants described affect the composition of the viral RNP to enhance
      viral protein synthesis.

PMID- 19091370
TI  - Substantial envelope-specific CD8 T-cell immunity fails to control SIV disease.
AB  - It is unknown which HIV proteins to target by vaccination in order to generate
      the most effective CD8 T-cell immunity. We recently immunized SIV(mac251)
      infected pigtail macaques with Gag peptides or a cocktail of peptides spanning
      all SIV proteins, including SIV Env. High-level SIV Env-specific CD8 T-cell
      responses were generated and 7 novel Env-specific CD8 T-cell epitopes in 10
      animals were mapped. Env-specific CD8 T-cell responses were significantly
      inferior to Gag-specific responses, and no better than unvaccinated control
      animals, in the control of SIV replication and prevention of disease. Escape
      mutations emerged within several Env-specific CTL epitopes, suggesting at least
      some pressure imparted by the Env CTL responses, but this did not correlate with
      significantly reduced SIV replication. We conclude Env-specific CTL may not be
      the most effective response to induce by vaccination.

PMID- 19091371
TI  - Fate and distribution of pharmaceuticals in wastewater and sewage sludge of the
      conventional activated sludge (CAS) and advanced membrane bioreactor (MBR)
      treatment.
AB  - In this paper we report on the performances of full-scale conventional activated
      sludge (CAS) treatment and two pilot-scale membrane bioreactors (MBRs) in
      eliminating various pharmaceutically active compounds (PhACs) belonging to
      different therapeutic groups and with diverse physico-chemical properties. Both
      aqueous and solid phases were analysed for the presence of 31 pharmaceuticals
      included in the analytical method. The most ubiquitous contaminants in the sewage
      water were analgesics and anti-inflammatory drugs ibuprofen (14.6-31.3 microg/L)
      and acetaminophen (7.1-11.4 microg/L), antibiotic ofloxacin (0.89-31.7 microg/L),
      lipid regulators gemfibrozil (2.0-5.9 microg/L) and bezafibrate (1.9-29.8
      microg/L), beta-blocker atenolol (0.84-2.8 microg/L), hypoglycaemic agent
      glibenclamide (0.12-15.9 microg/L) and a diuretic hydrochlorothiazide (2.3-4.8
      microg/L). Also, several pharmaceuticals such as ibuprofen, ketoprofen,
      diclofenac, ofloxacin and azithromycin were detected in sewage sludge at
      concentrations up to 741.1, 336.3, 380.7, 454.7 and 299.6 ng/g dry weight. Two
      pilot-scale MBRs exhibited enhanced elimination of several pharmaceutical
      residues poorly removed by the CAS treatment (e.g., mefenamic acid, indomethacin,
      diclofenac, propyphenazone, pravastatin, gemfibrozil), whereas in some cases more
      stable operation of one of the MBR reactors at prolonged SRT proved to be
      detrimental for the elimination of some compounds (e.g., beta-blockers,
      ranitidine, famotidine, erythromycin). Moreover, the anti-epileptic drug
      carbamazepine and diuretic hydrochlorothiazide by-passed all three treatments
      investigated. Furthermore, sorption to sewage sludge in the MBRs as well as in
      the entire treatment line of a full-scale WWTP is discussed for the encountered
      analytes. Among the pharmaceuticals encountered in sewage sludge, sorption to
      sludge could be a relevant removal pathway only for several compounds (i.e.,
      mefenamic acid, propranolol, and loratidine). Especially in the case of
      loratidine the experimentally determined sorption coefficients (Kds) were in the
      range 2214-3321 L/kg (mean). The results obtained for the solid phase indicated
      that MBR wastewater treatment yielding higher biodegradation rate could reduce
      the load of pollutants in the sludge. Also, the overall output load in the
      aqueous and solid phase of the investigated WWTP was calculated, indicating that
      none of the residual pharmaceuticals initially detected in the sewage sludge were
      degraded during the anaerobic digestion. Out of the 26 pharmaceutical residues
      passing through the WWTP, 20 were ultimately detected in the treated sludge that
      is further applied on farmland.

PMID- 19091372
TI  - The comparison of two heavy fuel oils in composition and weathering pattern,
      based on IR, GC-FID and GC-MS analyses: application to the Prestige wreackage.
AB  - This paper compares the weathering patterns of two similar fuel oils: a fuel oil
      spilled after a ship accident (Prestige-Nassau, off the Galician coast -NW Spain
      ) and a fuel designed to cope with the numerous quests for samples to carry out
      scientific studies (IFO). Comparative studies were made to evaluate the
      capability of common fingerprinting analytical techniques to differentiate the
      fuels, as well as their capabilities to monitor their weathering. The two
      products were spilled under controlled conditions during ca. four months to
      assess how they evolved on time. Mid-IR spectrometry and gas chromatography
      (flame ionization and mass spectrometry detectors) were used. IR indexes related
      to total aromaticity, type of substituents (branched or linear chains) and degree
      of aromatic substitution reflected well the differences between the fuels during
      weathering. Regarding the chromatographic measurements, the n-alkanes became
      highly reduced for both fuel oils and it was found that the PAHs of the synthetic
      fuel (IFO) were more resistant to weathering. Regarding biomarkers, the different
      profiles of the steranes, diasteranes and triaromatic steroids allowed for a
      simple differentiation amongst the two products. The %D2/P2 ratio differentiated
      both products whereas the %N3/P2 one ordered the samples according to the extent
      of their weathering.

PMID- 19091373
TI  - Unexpected isomeric equilibrium in pyridoxamine Schiff bases.
AB  - Pyridoxamine is a vitamin B(6) derivative involved in biological reactions such
      as transamination, and can also act as inhibitor in protein glycation. In both
      cases, it has been reported that Schiff base formation between pyridoxamine and
      carbonyl compounds is the main step. Nevertheless, few studies on the Schiff base
      formation have been reported to date. In this work, we conduct a comparative
      study of the reaction of pyridoxamine and 4-picolylamin (a pyridoxamine analog)
      with various carbonyl compounds including propanal, formaldehyde and pyruvic
      acid. Based on the results, 4-picolylamin forms a Schiff base as end-product of
      its reactions with propanal and pyruvic acid, but a carbinolamine with
      formaldehyde. On the other hand, pyridoxamine forms a Schiff base with the three
      reagents, but the end-product is in equilibrium with its hemiaminal form, which
      results from the attack of the phenolate ion of the pyridine ring on the imine
      carbon. This isomeric equilibrium should be considered in studying reactions
      involving amine derivatives of vitamin B(6).

PMID- 19091374
TI  - Exposure assessment of persistent organic pollutants and metals in Mexican
      children.
AB  - Environmental policies in Mexico have contributed to the reduction in the
      production or use of some persistent organic pollutants (POPs) and metals.
      However, monitoring of POPs concentrations in humans living in hot spots is
      lacking. Therefore, the objective of this study was to conduct a screening for
      POPs and metals first in Mexican children living in high-risk areas. During the
      year 2004, we analyzed a total of 229 healthy children (aged 6-12 years old) who
      resided in communities located in nine Mexican states. Organochlorine
      insecticides, PCBs and metals were quantified in plasma and urine samples. We
      detected p'p-DDE in all the children; moreover, p'p-DDT, lindane and
      hexachlorobenzene were detected respectively in 14%, 85% and 10% of the children
      studied. Measurable levels of PCBs were recorded in only one community, where six
      of 14 PCB congeners assayed were detected (numbers 52, 118, 138, 153, 170 and
      180). All the children had detectable levels of lead in their blood (mean level,
      4.6 microg dL(-1)); furthermore, 57% of the children studied had levels higher
      than 5.0 microg/dL. The mean level of urinary arsenic (UAs) for all the children
      was 22.35 microg g(-1) creatinine and 15% of those children had concentrations of
      UAs above 50 microg g(-1) creatinine. For cadmium, the mean urinary level was
      0.78 microg g(-1) creatinine, and only one percent of the children had values
      above 2.0 microg g(-1) creatinine. The results cannot be generalized since the
      communities selected are not representative of the Mexican population; however,
      they indicate that Mexican children are exposed to chemicals and some at risk
      levels.

PMID- 19091375
TI  - Estimation of amorphous organic carbon/water partition coefficients, subcooled
      liquid aqueous solubilities, and n-octanol/water partition coefficients of
      nonpolar chlorinated aromatic compounds from chlorine fragment constants.
AB  - This study aims to derive the relation between the number of chlorine atoms in
      chlorobenzenes, polychlorinated biphenyls (PCBs), dibenzo-p-dioxins (PCDDs), and
      dibenzofurans (PCDFs) and logK(oc) for linear partitioning between water and
      average amorphous organic carbon in soils or sediments. Because reliable
      determinations of logK(oc) are relatively sparse for chlorobenzenes and PCBs, and
      are even absent for PCDDs and PCDFs, a work-around solution was developed: First,
      the relation of n-octanol/water partitioning (K(ow)) and (subcooled) liquid
      solubility (S(l)) to the number of chlorines was investigated. Slopes for the
      linear correlation of logK(ow) with the number of chlorines (corrected for the
      number of ortho-chlorines in the case of PCBs) appeared identical for
      chlorobenzenes, PCBs, PCDDs, and PCDFs. Such was also the case for logS(l).
      Slopes for the linear relation of chlorobenzenes and PCB logK(oc) values with the
      number of chlorines were similar for the various soils and sediments, though
      intercepts were different. The ortho-chlorine correction factor for PCB logK(oc)
      was equal to the ortho-chlorine correction factor for PCB logK(ow) and logS(l).
      For PCDDs and PCDFs, a relation between logK(oc) and the number of chlorine atoms
      was derived by combining the chlorobenzenes/PCB logK(oc)-logK(ow) and logK(oc)
      logS(l) relationships with logK(ow) (or S(l))-chlorine number relations for PCDDs
      and PCDFs.

PMID- 19091376
TI  - Influences of various Pt dopants over surface platinized TiO2 on the
      photocatalytic oxidation of nitric oxide.
AB  - Various surface platinized TiO(2) were prepared by four different preparation
      methods and investigated with respect to their behaviors in UV photocatalytic
      oxidation of nitric oxide. The physicochemical properties of the Pt modified
      TiO(2) were investigated by X-ray diffraction analysis, X-ray photoelectron
      spectrum analysis, transmission electron microscopy, and photoluminescence
      spectra. From the experimental results, it was found that new electronic states
      were observed above the valence bands of PtOx-TiO(2) and PtClx-TiO(2). And the
      lifetime of electrons and holes was found prolonged in the PtOx-TiO(2) catalysts.
      The activity tests showed that the dopants existed as metallic Pt and platinum
      chloride had little contribution to the photocatalytic oxidation of NO in gas
      phase. However, the dopant which existed as PtOx could improve the NO
      photocatalytic oxidation efficiency and the reaction rate. The photocatalytic
      activity of the 0.05 at% PtOx-TiO(2) was nearly three times higher than that of
      the pure Degussa P25 with an inlet NO concentration of 200 ppm.

PMID- 19091377
TI  - Estimation of amorphous organic carbon/water partition coefficients, subcooled
      aqueous solubilities, and n-octanol/water distribution coefficients of
      alkylbenzenes and polycyclic aromatic hydrocarbons.
AB  - The aim of this work was to derive a relation between the number of specific
      carbon atoms in alkylbenzenes and PAHs and the average logK(oc) for linear
      partitioning between amorphous organic carbon in soils and sediments and water.
      The relation between the number of specific carbon atoms and n-octanol/water
      partitioning and subcooled aqueous solubility was sought first, as the number of
      data for partitioning into amorphous organic carbon was relatively sparse. It
      turned out that linear partitioning into amorphous organic carbon could be
      described by a linear relation based on the number of aromatic carbons, the
      number of alkyl carbons and the number of alicyclic carbons in the same way as
      for n-octanol/water partitioning and subcooled liquid aqueous solubility. From
      the linear regressions for linear partitioning into the various amorphous organic
      carbons, an average intercept for the linear partitioning regression equation was
      derived to represent average organic carbon in soils and sediments.

PMID- 19091378
TI  - Highly effective degradation of polychlorinated biphenyls in soil mediated by a
      Ca/Rh bicatalytic system.
AB  - Treatment of PCBs in soil using metallic calcium and alcohol ultimately reduced
      1300 x 10(-3)mgkg(-1) PCB concentration to 1.8 x 10(-3)mg kg(-1). Moreover, using
      the metallic calcium catalyst method to promote the effective use of hydrogen gas
      in the presence of a specific reducing catalyst such as Rh/C, the decomposition
      efficiency of PCBs was notably increased despite mild reaction conditions. The
      total PCB concentration of treated soils decreased from 1300 x 10(-3)mg kg(-1) to
      0.62 x 10(-3)mg kg(-1) (decomp. avg.=99.95%). Treatment of soils with metallic
      calcium and a Rh/C catalyst in alcohol under mild conditions such as 0.15-0.26
      MPa at room temperature is extremely effective for degradation of existing PCBs.

PMID- 19091379
TI  - Importance of elemental mercury in lake sediments.
AB  - Mercury (Hg) redox changes in sediments are poorly studied and understood, even
      though they potentially control Hg availability for methylation and can alter
      sediment-water Hg exchange. Elemental Hg (Hg(0)) concentrations in sediments of
      two Canadian Shield lakes were assessed by thermodesorption. Hg(0) concentrations
      in sediments varied between 6.3 and 60.3 pg g(-1) (wet weight) which represented
      7.4-28.4% of total mercury (HgT) concentration. Hg(0) concentrations were similar
      in both lakes. Hg(0) was rapidly adsorbed on sediments in controlled adsorption
      experiments and surface sediments sampled in summer had a stronger affinity for
      Hg(0) than deeper sediments and sediments sampled in fall. This adsorption was
      positively correlated to organic matter content and negatively related to
      particle grain size, pH and oxygen concentration in overlying water. This study
      demonstrates that Hg(0) is a prevalent species in sediments, but not in
      porewater, because of the high sorptive capacity of sediments towards Hg(0). Its
      potential availability towards Hg methylating bacteria remains to be determined.

PMID- 19091380
TI  - Spectroscopic characterization of dissolved organic matter isolated from
      rainwater.
AB  - Rainwater is a matrix containing extremely low concentrations (in the range of
      muM C) of dissolved organic carbon (DOC) and for its characterization, an
      efficient extraction procedure is essential. A recently developed procedure based
      on adsorption onto XAD-8 and XAD-4 resins in series was used in this work for the
      extraction and isolation of rainwater dissolved organic matter (DOM). Prior to
      the isolation and fractionation of DOM, and to obtain sufficient mass for the
      spectroscopic analyses, individual rainwater samples were batched together
      according to similar meteorological conditions on a total of three composed
      samples. The results of the isolation procedure indicated that the resin tandem
      procedure is not applicable for rainwater DOM since the XAD-4 resin caused
      samples contamination. On the other hand, the XAD-8 resin allowed DOM recoveries
      of 39.9-50.5% of the DOC of the original combined samples. This recovered organic
      fraction was characterized by UV-visible, molecular fluorescence, FTIR-ATR and 1H
      NMR spectroscopies. The chemical characterization of the rainwater DOM showed
      that the three samples consist mostly of hydroxylated and carboxylic acids with a
      predominantly aliphatic character, containing a minor component of aromatic
      structures. The obtained results suggest that the DOM in rainwater, and
      consequently in the precursor atmospheric particles, may have a secondary origin
      via the oxidation of volatile organic compounds from different origins.

PMID- 19091381
TI  - Organic residues as immobilizing agents in aided phytostabilization: (II) effects
      on soil biochemical and ecotoxicological characteristics.
AB  - Sewage sludge (SS), municipal solid waste compost, and garden waste compost (GWC)
      were used as immobilizing agents in aided phytostabilization of an acid metal
      contaminated soil affected by mining activities. The organic residues were
      applied at 25, 50 and 100 Mg ha(-1) (dry weight basis) and perennial ryegrass
      (Lolium perenne L.) was used as a "green cover". We studied the effects of the
      treatments on soil phytotoxicity and enzymatic activities, and on the composition
      and toxicity of the soil leachate towards Vibrio fischeri and Daphnia magna.
      Application of SS led to the greatest values of dehydrogenase, acid phosphatase,
      beta-glucosidase, protease and urease activities, corresponding to the greatest
      overall microbial and biochemical activity in amended soils. Conversely, GWC did
      not increase these enzymatic activities, relative to the unamended soil, or
      enhance ryegrass growth. Cellulase activity increased with increasing application
      rates of the amendments tested, but decreased at the highest SS application rate.
      The organic amendments were able to suppress soil toxicity to levels that did not
      affect D. magna, when applied at 50 and 100 Mg ha(-1), but SS, at the same
      application rates, increased the soil leachate toxicity towards V. fischeri.
      Moreover, ryegrass showed some phytotoxic symptoms when 100 Mg ha(-1) of SS were
      applied. This study showed the importance of an integrated evaluation of soil
      quality on remediation processes. Although SS immobilized trace metals and
      corrected soil acidity, improving soil biochemical status, when used at high
      application rates it led to toxicity of soil leachate towards V. fischeri,
      decreased soil cellulase activity and impaired ryegrass growth.

PMID- 19091382
TI  - The pollution characteristics of odor, volatile organochlorinated compounds and
      polycyclic aromatic hydrocarbons emitted from plastic waste recycling plants.
AB  - Plastic waste treatment trends toward recycling in many countries; however, the
      melting process in the facilities which adopt material recycling method for
      treating plastic waste may emit toxicants and cause sensory annoyance. The
      objectives of this study were to analyze the pollution characteristics of the
      emissions from the plastic waste recycling plants, particularly in harmful
      volatile organochlorinated compounds, polycyclic aromatic hydrocarbons (PAHs),
      odor levels and critical odorants. Ten large recycling plants were selected for
      analysis of odor concentration (OC), volatile organic compounds (VOCs) and PAHs
      inside and outside the plants using olfactometry, gas chromatography-mass
      spectrometry and high performance liquid chromatography-fluorescence detector,
      respectively. The olfactometric results showed that the melting processes used
      for treating polyethylene/polypropylene (PE/PP) and polyvinyl chloride (PVC)
      plastic waste significantly produced malodor, and the odor levels at downwind
      boundaries were 100-229 OC, which all exceeded Taiwan's EPA standard of 50 OC.
      Toluene, ethylbenzene, 4-methyl-2-pentanone, methyl methacrylate and acrolein
      accounted for most odors compared to numerous VOCs. Sixteen organochlorinated
      compounds were measured in the ambient air emitted from the PVC plastic waste
      recycling plant and total concentrations were 245-553 microg m(-3); most were
      vinyl chloride, chloroform and trichloroethylene. Concentrations of PAHs inside
      the PE/PP plant were 8.97-252.16 ng m(-3), in which the maximum level were 20
      fold higher than the levels detected from boundaries. Most of these recycling
      plants simply used filter to treat the melting fumes, and this could not
      efficiently eliminate the gaseous compounds and malodor. Improved exhaust air
      pollution control were strongly recommended in these industries.

PMID- 19091383
TI  - A method for upscaling soil parameters for use in a dynamic modelling assessment
      of water quality in the Pyrenees.
AB  - Dynamic modelling of hydrochemistry is a valuable tool to study and predict the
      recovery of surface waters from acidification, and to assess the effects of
      confounding factors (such as delayed soil response and changing climate) that
      cause hysteresis during reversal from acidification. The availability of soil
      data is often a limitation for the regional application of dynamic models. Here
      we present a method to upscale site-specific soil properties to a regional scale
      in order to circumvent that problem. The method proposed for upscaling relied on
      multiple regression models between soil properties and a suite of environmental
      variables used as predictors. Soil measurements were made during a field survey
      in 13 catchments in the Pyrenees (NW Spain). The environmental variables were
      derived from mapped or remotely sensed topographic, lithological, land-cover, and
      climatic information. Regression models were then used to model soil parameters,
      which were supplied as input for the biogeochemical model MAGIC (Model for
      Acidification of Groundwater In Catchments) in order to reconstruct the history
      of acidification in Pyrenean lakes and forecast the recovery under a scenario of
      reduced acid deposition. The resulting simulations were then compared with model
      runs using field measurements as input parameters. These comparisons showed that
      regional averages for the key water and soil chemistry variables were suitably
      reproduced when using the modelled parameters. Simulations of water chemistry at
      the catchment scale also showed good results, whereas simulated soil parameters
      reflected uncertainty in the initial modelled estimates.

PMID- 19091384
TI  - Photochemical trajectory modelling of ozone during the summer PUMA campaign in
      the UK West Midlands.
AB  - A Photochemical Trajectory Model (PTM), coupled with the Master Chemical
      Mechanism, is set up for summertime conditions and used to simulate pollutant
      levels measured in Birmingham, UK during the summer Pollution in the Urban
      Midlands Atmosphere (PUMA) campaign. In general, ozone is modelled well by the
      PTM, with reasonably good correlation and approximately 90% of afternoon and
      evening concentrations within a factor of two of measurements. The contribution
      of local biogenic emissions in the West Midlands to ozone formation during this
      period was also assessed and found to be of minor importance. Initially, the
      ozone episode of 26th June 1999, where levels of up to 87 ppb were observed was
      not reproduced by the UK PTM model. Sensitivity studies showed that the major
      cause for this was transport uncertainty in the origin and pathway of the air
      during conditions of slow moving anticyclonic conditions. The results indicate
      that the ozone episode was caused by recirculation of air polluted within the UK,
      with additional precursor emissions over the Netherlands, Belgium and France.

PMID- 19091385
TI  - Metal supplementation to UASB bioreactors: from cell-metal interactions to full
      scale application.
AB  - Upflow anaerobic sludge bed (UASB) bioreactors are commonly used for anaerobic
      wastewater treatment. Trace metals need to be dosed to these bioreactors to
      maintain microbial metabolism and growth. The dosing needs to balance the supply
      of a minimum amount of micronutrients to support a desired microbial activity or
      growth rate with a maximum level of micronutrient supply above which the trace
      metals become inhibitory or toxic. In studies on granular sludge reactors, the
      required micronutrients are undefined and different metal formulations with
      differences in composition, concentration and species are used. Moreover, an
      appropriate quantification of the required nutrient dosing and suitable ranges
      during the entire operational period has been given little attention. This review
      summarizes the state-of-the-art knowledge of the interactions between trace
      metals and cells growing in anaerobic granules, which is the main type of biomass
      retention in anaerobic wastewater treatment reactors. The impact of trace metal
      limitation as well as overdosing (toxicity) on the biomass is overviewed and the
      consequences for reactor performance are detailed. Special attention is given to
      the influence of metal speciation in the liquid and solid phase on
      bioavailability. The currently used methods for trace metal dosing into
      wastewater treatment reactors are overviewed and ways of optimization are
      suggested.

PMID- 19091386
TI  - Reconstruction of the thermal environment evolution in urban areas from
      underground temperature distribution.
AB  - It is possible to estimate the ground surface temperature (GST) history of the
      past several hundred years from temperature profiles measured in boreholes
      because the temporal variation in GST propagates into the subsurface by thermal
      diffusion. This "geothermal method" of reconstructing GST histories can be
      applied to studies of thermal environment evolution in urban areas, including the
      development of "heat islands." Temperatures in boreholes were logged at 102 sites
      in Bangkok, Jakarta, Taipei, Seoul and their surrounding areas in 2004 to 2007.
      The effects of recent surface warming can be recognized in the shapes of most of
      the obtained temperature profiles. The preliminary results of reconstruction of
      GST histories through inversion analysis show that GST increased significantly in
      the last century. Existing temperature profile data for the areas in and around
      Tokyo and Osaka can also be used to reconstruct GST histories. Because most of
      these cities are located on alluvial plains in relatively humid areas, it is
      necessary to use a model with groundwater flow and a layered subsurface structure
      for reconstruction analysis. Long-term records of subsurface temperatures at
      multiple depths may demonstrate how the GST variation propagates downward through
      formations. Time series data provide information on the mechanism of heat
      transfer (conduction or advection) and the thermal diffusivity. Long-term
      temperature monitoring has been carried out in a borehole located on the coast of
      Lake Biwa, Japan. Temperatures at 30 and 40 m below the ground surface were
      measured for 4 years and 2 years, respectively, with a resolution of 1 mK. The
      obtained records indicate steady increases at both depths with different rates,
      which is probably the result of some recent thermal event(s) near the surface.
      Borehole temperatures have also been monitored at selected sites in Bangkok,
      Jakarta, and Taiwan.

PMID- 19091387
TI  - Nervous regulation of internal organs in fishes. Preface.

PMID- 19091388
TI  - Incidence and management of pancreatic leaks after splenectomy with distal
      pancreatectomy performed during primary cytoreductive surgery for advanced
      ovarian, peritoneal and fallopian tube cancer.
AB  - OBJECTIVE: To determine the incidence, management, and outcome of patients
      diagnosed with a pancreatic leak after a distal pancreatectomy during primary
      surgical cytoreduction for ovarian, peritoneal, or tubal cancer. METHODS: We
      performed a retrospective chart review of all patients who had a distal
      pancreatectomy at the time of primary surgery. Charts were reviewed to identify
      those patients who developed a persistent left upper quadrant abdominal fluid
      collection with elevated amylase levels. RESULTS: A total of 17 patients had a
      distal pancreatectomy; of these, 4 patients (24%) developed a postoperative
      pancreatic leak. In these patients, persistent leukocytosis prompted evaluation
      with a computed tomography scan, which subsequently revealed a fluid collection.
      The median time from surgery to drainage of this collection was 9 days (range, 8
      66). The drain remained in situ for a median of 29 days (range, 22-82). The
      median amylase level of the fluid was 22,945 U/L (range, 763-47,250). The median
      length of hospital stay for those patients with a leak was 33 days (range, 25
      44), which was longer than those without a leak. However, the median time from
      surgery to treatment with systemic chemotherapy was 31 days (range, 16-43), which
      was equivalent to those without a pancreatic leak. CONCLUSION: Twenty-four
      percent of patients who had undergone a distal pancreatectomy developed a
      pancreatic leak. This complication, which usually presents early in the
      postoperative period, can be managed conservatively with percutaneous drainage.
      Oral intake may be resumed, and total parenteral nutrition is not needed in the
      majority of cases. Systemic chemotherapy can be administered without significant
      delay.

PMID- 19091389
TI  - Apoptosis in fresh and cryopreserved buffalo sperm.
AB  - The objectives of present study were (a) validation of annexin V/PI assay for
      estimation of sperm apoptosis in buffalo (Experiment 1) and (b) determining the
      effect of stages of cryopreservation on sperm apoptosis and its correlation with
      sperm motility and plasma membrane integrity (Experiment 2). In Experiment 1,
      different levels of apoptosis were artificially induced in buffalo semen
      (100x10(6)sperm/aliquot) through graded doses of camptothecin (5, 10 and
      20microM/aliquot). Higher concentrations of camptothecin (10 and 20microM)
      successfully (P<0.05) induced apoptosis as compared to the lower (5microM) dose
      and/or control. In Experiment 2, semen samples (n=9, three pooled semen samples
      from each of the three buffalo bulls separately) were cryopreserved using vapor
      freezing. The mean percentage of apoptotic, necrotic and viable sperm did not
      differ between fresh and before freezing stages. However, freezing and thawing
      increased (P<0.05) the percentage of apoptotic sperm (25.4+/-0.6 vs. 36.5+/-1.9)
      while decreased (P<0.05) the necrotic (35.1+/-1.2 vs. 29.7+/-0.7) and viable
      sperm (37.2+/-1.3 vs. 32.8+/-1.9, (P<0.07). Likewise, the mean percent motility
      and plasma membrane integrity decreased (P<0.05) (64+/-2.1 vs. 49.4+/-1.3) and
      (79.6+/-0.5 vs. 38.7+/-0.3) respectively, at post thaw compared to other stages.
      Coefficient of correlation, combined at all stages for each variable revealed
      that sperm apoptosis was inversely correlated with sperm motility and plasma
      membrane integrity. It is concluded that (a) the annexin V/PI assay can be used
      as a tool to determine the buffalo semen apoptosis and (b) freezing and thawing
      induces apoptosis in buffalo sperm.

PMID- 19091390
TI  - Contrast of hand preferences between communicative gestures and non-communicative
      actions in baboons: implications for the origins of hemispheric specialization
      for language.
AB  - Gestural communication is a modality considered in the literature as a candidate
      for determining the ancestral prerequisites of the emergence of human language.
      As reported in captive chimpanzees and human children, a study in captive baboons
      revealed that a communicative gesture elicits stronger degree of right-hand bias
      than non-communicative actions. It remains unclear if it is the communicative
      nature of this manual behavior which induces such patterns of handedness. In the
      present study, we have measured hand use for two uninvestigated behaviors in a
      group of captive olive baboons: (1) a non-communicative self-touching behavior
      ("muzzle wipe" serving as a control behavior), (2) another communicative gesture
      (a ritualized "food beg") different from the one previously studied in the
      literature (a species-specific threat gesture, namely "hand slap") in the same
      population of baboons. The hand preferences for the "food beg" gestures revealed
      a trend toward right-handedness and significantly correlated with the hand
      preferences previously reported in the hand slap gesture within the same baboons.
      By contrast, the hand preferences for the self-touching behaviors did not reveal
      any trend of manual bias at a group-level nor correlation with the hand
      preferences of any communicative gestures. These findings provide additional
      support to the hypothesized existence in baboons of a specific communicative
      system involved in the production of communicative gestures that may tend to a
      left-hemispheric dominance and that may differ from the system involved in purely
      motor functions. The hypothetical implications of these collective results are
      discussed within the theoretical framework about the origins of hemispheric
      specialization for human language.

PMID- 19091391
TI  - Assessing bleeds clinically: what's the score?

PMID- 19091392
TI  - Radiotherapy in locally advanced prostate cancer.

PMID- 19091393
TI  - Outpatient management of patients with low-risk upper-gastrointestinal
      haemorrhage: multicentre validation and prospective evaluation.
AB  - BACKGROUND: Upper-gastrointestinal haemorrhage is a frequent reason for hospital
      admission. Although most risk scoring systems for this disorder incorporate
      endoscopic findings, the Glasgow-Blatchford bleeding score (GBS) is based on
      simple clinical and laboratory variables; a score of 0 identifies low-risk
      patients who might be suitable for outpatient management. We aimed to evaluate
      the GBS then assess the effect of a protocol based on this score for non
      admission of low-risk individuals. METHODS: Our study was undertaken at four
      hospitals in the UK. We calculated GBS and admission (pre-endoscopy) and full
      (post-endoscopy) Rockall scores for consecutive patients presenting with upper
      gastrointestinal haemorrhage. With receiver-operating characteristic (ROC)
      curves, we compared the ability of these scores to predict either need for
      clinical intervention or death. We then prospectively assessed at two hospitals
      the introduction of GBS scoring to avoid admission of low-risk patients.
      FINDINGS: Of 676 people presenting with upper-gastrointestinal haemorrhage, we
      identified 105 (16%) who scored 0 on the GBS. For prediction of need for
      intervention or death, GBS (area under ROC curve 0.90 [95% CI 0.88-0.93]) was
      superior to full Rockall score (0.81 [0.77-0.84]), which in turn was better than
      the admission Rockall score (0.70 [0.65-0.75]). When introduced into clinical
      practice, 123 patients (22%) with upper-gastrointestinal haemorrhage were
      classified as low risk, of whom 84 (68%) were managed as outpatients without
      adverse events. The proportion of individuals with this condition admitted to
      hospital also fell (96% to 71%, p<0.00001). INTERPRETATION: The GBS identifies
      many patients presenting to general hospitals with upper-gastrointestinal
      haemorrhage who can be managed safely as outpatients. This score reduces
      admissions for this condition, allowing more appropriate use of in-patient
      resources.

PMID- 19091395
TI  - The effect of nocodazole on the transfection efficiency of lipid-bilayer coated
      gold nanoparticles.
AB  - Nonviral vectors are safer than viral systems for gene therapy applications.
      However, the limited efficacy always prevents their being widely used in clinical
      practice. Aside from searching new gene nonviral vectors, many researchers focus
      on finding out new substances to improve the transfection efficiency of existent
      vectors. In this work, we found a transfection enhancer, nocodazole (NCZ), for
      dimethyldioctadecylammonium (DODAB, a cationic lipid) bilayer coated gold
      nanoparticles (AuNPs) mediated gene delivery. It was found that NCZ produces 3
      fold transfection enhancement to HEK 293T cells assessed by flow cytometry (FCM).
      The result was further confirmed by luciferase assay, in which NCZ induced more
      than 5 times improvement in transfection efficiency after 48 h of transfection.
      The results from the inductively coupled plasma mass spectrometry (ICP-MS) and
      FCM showed that NCZ did not affect the internalization of DODAB-AuNPs/DNA
      complexes. The trafficking of the complexes by transmission electron microscopy
      (TEM) indicated that the interrupted transportation of the complexes to the
      lysosomes contributed greatly to the transfection enhancement. Therefore, NCZ can
      be used as a transfection enhancer in DODAB-AuNPs mediated transfection system.
      This work also gave an insight to improving the efficiency of lipid-mediated
      transfection: modifying lipid on gold nanoparticles and pre-treating cells by NCZ
      before the transfection.

PMID- 19091396
TI  - Dynamic processes involved in the pre-vascularization of silk fibroin constructs
      for bone regeneration using outgrowth endothelial cells.
AB  - For successful bone regeneration tissue engineered bone constructs combining both
      aspects, namely a high osteogenic potential and a rapid connection to the
      vascular network are needed. In this study we assessed the formation of pre
      vascular structures by human outgrowth endothelial cells (OEC) from progenitors
      in the peripheral blood and the osteogenic differentiation of primary human
      osteoblasts (pOB) on micrometric silk fibroin scaffolds. The rational was to gain
      more insight into the dynamic processes involved in the differentiation and
      functionality of both cell types depending on culture time in vitro. Vascular
      tube formation by OEC was assessed quantitatively at one and 4 weeks of culture.
      In parallel, we assessed the temporal changes in cell ratios by flow cytometry
      and in the marker profiles of endothelial and osteogenic markers by quantitative
      real-time PCR. In terms of OEC, we observed an increase in tube length, tube
      area, number of nodes and number of vascular meshes within a culture period of 4
      weeks, but a decrease in endothelial markers in real-time PCR. At the same time
      early osteogenic markers were downregulated, while marker expression associated
      with progressing mineralized matrix was upregulated in later stages of the
      culture. In addition, deposition of matrix components, such as collagen type I,
      known as a pro-angiogenic substrate for endothelial cells, appeared to increase
      with time indicated by immunohistochemistry. In summary, the study suggests a
      progressing maturation of the tissue construct with culture time which seems to
      be not effected by culture conditions mainly designed for outgrowth endothelial
      cells.

PMID- 19091394
TI  - Endocrine treatment, with or without radiotherapy, in locally advanced prostate
      cancer (SPCG-7/SFUO-3): an open randomised phase III trial.
AB  - BACKGROUND: Several studies have shown the efficacy of endocrine therapy in
      combination with radiotherapy in high-risk prostate cancer. To assess the effect
      of radiotherapy, we did an open phase III study comparing endocrine therapy with
      and without local radiotherapy, followed by castration on progression. METHODS:
      This randomised trial included men from 47 centres in Norway, Sweden, and
      Denmark. Between February, 1996, and December, 2002, 875 patients with locally
      advanced prostate cancer (T3; 78%; PSA<70; N0; M0) were centrally randomly
      assigned by computer to endocrine treatment alone (3 months of total androgen
      blockade followed by continuous endocrine treatment using flutamide; 439
      patients), or to the same endocrine treatment combined with radiotherapy (436
      patients). The primary endpoint was prostate-cancer-specific survival, and
      analysis was by intention to treat. This study is registered as an international
      standard randomised controlled trial, number ISRCTN01534787. FINDINGS: After a
      median follow-up of 7.6 years, 79 men in the endocrine alone group and 37 men in
      the endocrine plus radiotherapy group had died of prostate cancer. The cumulative
      incidence at 10 years for prostate-cancer-specific mortality was 23.9% in the
      endocrine alone group and 11.9% in the endocrine plus radiotherapy group
      (difference 12.0%, 95% CI 4.9-19.1%), for a relative risk of 0.44 (0.30-0.66). At
      10 years, the cumulative incidence for overall mortality was 39.4% in the
      endocrine alone group and 29.6% in the endocrine plus radiotherapy group
      (difference 9.8%, 0.8-18.8%), for a relative risk of 0.68 (0.52-0.89). Cumulative
      incidence at 10 years for PSA recurrence was substantially higher in men in the
      endocrine-alone group (74.7%vs 25.9%, p<0.0001; HR 0.16; 0.12-0.20). After 5
      years, urinary, rectal, and sexual problems were slightly more frequent in the
      endocrine plus radiotherapy group. INTERPRETATION: In patients with locally
      advanced or high-risk local prostate cancer, addition of local radiotherapy to
      endocrine treatment halved the 10-year prostate-cancer-specific mortality, and
      substantially decreased overall mortality with fully acceptable risk of side
      effects compared with endocrine treatment alone. In the light of these data,
      endocrine treatment plus radiotherapy should be the new standard.

PMID- 19091397
TI  - Calcification by MC3T3-E1 cells on RGD peptide immobilized on titanium through
      electrodeposited PEG.
AB  - The effect of a cell-adhesive peptide containing Arg-Gly-Asp (RGD) immobilized
      through poly(ethylene glycol) (PEG) on titanium (Ti) on calcification by MC3T3-E1
      cells was investigated to develop a new surface modification technique using
      biofunctional molecules. RGD was immobilized on Ti through PEG, both terminals of
      which were terminated with -NH(2) and -COOH to combine with the Ti surface and
      RGD. PEG was immobilized on Ti with electrodeposition, and RGD, with immersion.
      For comparison, glycine was employed because it is the simplest molecule
      containing both -NH(2) and -COOH at its terminals. MC3T3-E1 cells were cultured
      and differentiation-induced on each specimen, and the cell calcification
      properties were investigated. As a result, there was no significant difference in
      the morphology and extension of MC3T3-E1 cells cultured on each specimen, while
      the number of cells cultured on RGD/PEG/Ti was the largest. After differentiation
      induction, there was no significant difference in the ALP activity among all
      specimens. On the other hand, the level of cell calcification on RGD/PEG/Ti was
      the highest. Therefore, the hard tissue compatibility of Ti is improved by
      immobilizing RGD through functional molecules which have a long molecular chain.

PMID- 19091398
TI  - The correlation of pore morphology, interconnectivity and physical properties of
      3D ceramic scaffolds with bone ingrowth.
AB  - In the design of tissue engineering scaffolds, design parameters including pore
      size, shape and interconnectivity, mechanical properties and transport properties
      should be optimized to maximize successful inducement of bone ingrowth. In this
      paper we describe a 3D micro-CT and pore partitioning study to derive pore scale
      parameters including pore radius distribution, accessible radius, throat radius,
      and connectivity over the pore space of the tissue engineered constructs. These
      pore scale descriptors are correlated to bone ingrowth into the scaffolds.
      Quantitative and visual comparisons show a strong correlation between the local
      accessible pore radius and bone ingrowth; for well connected samples a cutoff
      accessible pore radius of approximately 100 microM is observed for ingrowth. The
      elastic properties of different types of scaffolds are simulated and can be
      described by standard cellular solids theory: (E/E(0))=(rho/rho(s))(n). Hydraulic
      conductance and diffusive properties are calculated; results are consistent with
      the concept of a threshold conductance for bone ingrowth. Simple simulations of
      local flow velocity and local shear stress show no correlation to in vivo bone
      ingrowth patterns. These results demonstrate a potential for 3D imaging and
      analysis to define relevant pore scale morphological and physical properties
      within scaffolds and to provide evidence for correlations between pore scale
      descriptors, physical properties and bone ingrowth.

PMID- 19091399
TI  - The relationship between the mechanical properties and cell behaviour on PLGA and
      PCL scaffolds for bladder tissue engineering.
AB  - Previous work on 2D synthetic films showed growth of human bladder stromal cells
      was enhanced on materials with lower moduli that mimic the elastic properties of
      native tissue. This study developed 3D synthetic foam scaffolds for soft tissue
      engineering by emulsion freeze-drying. Foams of poly(lactide-co-glycolide) (PLGA)
      and poly(epsilon-caprolactone) (PCL) were extensively characterised using
      scanning electron microscopy, mercury porosimetry, dynamic mechanical analysis,
      degradation analysis, size exclusion chromatography and differential scanning
      calorimetry. Foams of 85-88% porosity and 35 microm pore diameter were selected
      for further study; the storage modulus of PCL foams was around half that of PLGA
      (2 MPa vs 4 MPa) and closer to the reported value for native bladder tissue.
      Urinary tract stromal cells showed a 4.4 and 2.4-fold higher attachment and rate
      of growth, respectively, on PCL scaffolds, as assessed by a modified 3-[4,5
      dimethyl(thiazol-2yl)-3,5-diphery] tetrazolium bromide assay. A greater
      contractile force was exerted by cells seeded in PLGA than on PCL scaffolds,
      raising the possibility that the reduced rate of proliferation of cells on PLGA
      scaffolds may reflect differentiation into a contractile phenotype. This study
      has generated PCL foam scaffolds with properties that may be pertinent to the
      tissue engineering of the bladder and other soft tissues.

PMID- 19091400
TI  - Bioactive enzyme-metal composites: the entrapment of acid phosphatase within gold
      and silver.
AB  - This paper is concerned with the entrapment of an enzyme within an aggregated
      metallic matrix and the development of a bioactive enzyme-metal composite.
      Whereas the use of organic polymers and metal oxides for the preparation of
      enzymatically active materials is well developed, the third principle enzyme
      material combination, namely protein-metal bulk, has not yet been reported. A new
      methodology for the entrapment of organic molecules and polymers within metals
      has been employed for the preparation of bioactive acid phosphatase@gold and acid
      phosphatase@silver, according to which room temperature reduction of the metal
      cation is carried out in the presence of the enzyme to be entrapped.
      Protectability of the entrapped enzyme against harsh conditions is shown: the
      acidic enzyme is kept alive under basic conditions.

PMID- 19091401
TI  - The role of phagosomal pH on the size-dependent efficiency of cross-presentation
      by dendritic cells.
AB  - Vaccines able to stimulate CD8(+) T cells are crucial in controlling a broad
      range of infectious diseases and tumors. To induce effective CD8(+) T cell
      responses, exogenous antigen has to be cross-presented onto major
      histocompatibility complex (MHC) class I molecules by dendritic cells. Although
      particle size has been recognized as a critical factor of vaccine design, it is
      unclear how the size of vaccine carriers impacts the intracellular processing of
      exogenous antigen and cross-presentation onto MHC class I molecules. In this
      study, by using polystyrene beads with narrowly defined sizes as model antigen
      carriers, we demonstrate that particle size mediates the efficiency of cross
      presentation of exogenous antigens. By examining the intracellular trafficking,
      kinetics of phagosomal pH and degradation of antigens bounded to beads, we
      illustrate the possible mechanisms attributed to the profound effect of particle
      size on the efficiency of cross-presentation. Antigen bounded to 50 nm beads was
      shuttled rapidly to an acidic environment within half an hour post-exposure to
      cells, leading to its rapid and unregulated degradation and inefficient cross
      presentation. In contrast, antigen bounded to 500 nm and 3 microm beads remained
      in a more neutral environment, which preserved the majority of antigens, leaving
      it available for the generation of peptides to be loaded onto MHC class I
      molecules. We conclude that the size of antigen carriers plays a critical role in
      directing antigen to the class I antigen presentation pathway. Our results,
      together with previous in vivo studies on the effect of particle size on CD8(+) T
      cell responses, provide insight into the rational design of vaccines for the
      stimulation of cell-mediated immunity.

PMID- 19091402
TI  - Regulation of protein expression and function of octn2 in forskolin-induced
      syncytialization in BeWo Cells.
AB  - Placental OCTN2 is a high-affinity carnitine transporter that can interact with a
      number of therapeutic agents. The process of syncytialization is associated with
      the expression of a variety of genes. However, the association between
      syncytialization and OCTN2 expression is not yet clear. Given that forskolin
      induces BeWo cells to undergo biochemical and morphological differentiation, the
      purpose of the present study was to investigate whether the function and
      expression of OCTN2 are influenced by forskolin treatment during
      syncytialization. The forskolin-induced differentiation of BeWo cells was
      validated by secretion of beta-human chorionic gonadotropin (beta-hCG) and
      syncytin expression. Cellular localization of OCTN2 was analyzed by confocal
      microscopy. Expression of OCTN2 and the modular proteins PDZK1, PDZK2, NHERF1 and
      NHERF2 was analyzed by Western blotting and carnitine uptake by BeWo cells was
      estimated and the kinetic properties of uptake measured. The results showed that
      forskolin treatment increased beta-hCG secretion and syncytin expression,
      suggesting induction of syncytialization. Confocal images of BeWo cells showed
      the localization of OCTN2 in the brush-border membrane. OCTN2 protein expression
      was upregulated in isolated brush-border membranes by long-term forskolin
      treatment, but the V(m) for carnitine uptake was unchanged, although the K(m)
      increased. PDZK1, NHERF1 and NHERF2 protein expression in the brush-border
      membrane was downregulated by forskolin treatment, whereas PDZK2 levels remained
      unchanged. In conclusion, protein expression and function of OCTN2 in BeWo cells
      can be regulated by forskolin treatment. While the presence of forskolin results
      in an increase in OCTN2 protein expression, the increase in uptake capacity may
      be compensated by the decreased expression of PDZK1, NHERF1 or NHERF2.

PMID- 19091403
TI  - Molecular response to imatinib in patient with Ph negative p190 BCR-ABL
      transcript positive chronic myeloid leukemia with cyclic leukocytosis.
AB  - An atypical case of Philadelphia (Ph) negative, e1a2 BCR-ABL transcript positive
      chronic myeloid leukemia (CML) characterized with cyclic periodic leukocytosis
      and spontaneous remissions is reported. The patient was treated with imatinib and
      good hematology response with molecular remission was achieved. So far, only few
      Ph positive CML patients expressing p190 BCR-ABL protein and different clinical
      characteristics and treatment have been described in the literature. This is the
      first report of Philadelphia negative, p190 BCR-ABL positive CML with cyclic
      spontaneous oscillation of white blood cell count (WBC), and excellent response
      to imatinib treatment.

PMID- 19091404
TI  - Notch-1 regulates Akt signaling pathway and the expression of cell cycle
      regulatory proteins cyclin D1, CDK2 and p21 in T-ALL cell lines.
AB  - Gain-of-function mutations in Notch-1 are common in T-cell lymphoblastic leukemia
      (T-ALL), making this receptor a promising target for drugs such as gamma
      secretase inhibitors (GSIs). However, GSIs seem to be active in only a small
      fraction of T-ALL cell lines with constitutive Notch-1 activity and the
      downstream response of Notch signaling is only partially understood. To further
      investigate the molecular mechanisms underlying proliferation suppression and
      apoptosis and explore effective downstream target genes, we used RNA interference
      (RNAi) technology to down-regulate the expression of Notch-1 in GSIs-resistant T
      ALL cell lines. Results showed that down-regulation of Notch-1 by transfection of
      a small interfering RNA (siRNA) could cause SupT1 cells proliferation inhibition
      by inducing G(0)/G(1) cell cycle arrest and apoptosis. The proliferation
      inhibitory and apoptotic effects resulting from down-regulation of Notch-1 may be
      mediated through regulating the expression of cell cycle regulatory proteins
      cyclin D1, CDK2 and p21 and the activity of Akt signaling. In addition, our
      results demonstrated that down-regulation of Notch-1 signaling could sensitize
      SupT1 cells to adriamycin. Taken together, cell cycle regulatory proteins and Akt
      signaling may be attractive targets in T-ALL.

PMID- 19091405
TI  - CXCR4 in acute myelogenous leukemia (AML): when too much attraction is bad for
      you.

PMID- 19091406
TI  - Facial nerve injury during external dacryocystorhinostomy.
AB  - OBJECTIVE: To describe weakness of the orbicularis oculi muscle after external
      dacryocystorhinostomy (DCR) and propose an anatomic explanation for the
      complication. DESIGN: Retrospective, observational study. PARTICIPANTS: Sixteen
      patients (13 female, 3 male) with a mean age of 60 years (median, 61 years;
      range, 34-85 years). METHODS: A retrospective chart review was performed of
      consecutive patients who had nasolacrimal duct obstruction repair by external
      DCR. Patients were identified who developed postoperative orbicularis oculi
      muscle weakness that manifested as hypometric blink or lagophthalmos with or
      without punctate keratopathy on the operated side. Patient parameters collected
      included demographic data, type of incision, incision length, use of lacrimal
      stent, length of follow-up, intraoperative and postoperative complications, and
      time to resolution of clinical findings. Statistical analysis was performed using
      a 2-tailed Fisher exact test with clinical significance designated at alpha =
      0.05. MAIN OUTCOME MEASURES: Identification of patients with orbicularis oculi
      muscle weakness after external DCR, documentation of incision type, clinical
      findings, and recovery of function. RESULTS: Among 215 patients and 247
      surgeries, 16 individuals (7.4%) were identified who demonstrated abnormalities
      of eyelid closure in the postoperative period after external DCR. Of these, 13
      patients had lagophthalmos with or without hypometric blink and 3 patients had
      hypometric blink alone. Eleven patients underwent surgery through a nasojugal
      incision, 4 patients underwent surgery through a vertical incision, and 1 patient
      underwent surgery through an eyelid margin incision. The degree of postoperative
      lagophthalmos was on average 1.5 mm. Four patients developed punctate
      keratopathy. Follow-up ranged from 3 to 50 weeks (mean, 20 weeks). Resolution of
      lagophthalmos was seen on average by 14 weeks with the longest time to resolution
      of 32 weeks. Three individuals continued to have residual hypometric blink at the
      time of last follow-up. CONCLUSIONS: Damage to peripheral fibers of the zygomatic
      and buccal branches of the facial nerve as they course through the medial canthal
      area to innervate the upper eyelid orbicularis oculi muscle may occur during
      external DCR surgery. Such injury may be responsible for orbicularis oculi muscle
      weakness manifesting as postoperative abnormal eyelid closure and lagophthalmos.
      In our cohort of patients, these findings were temporary and typically resolved
      in several months.

PMID- 19091407
TI  - Quality of life in high myopia: implantable Collamer lens implantation versus
      contact lens wear.
AB  - PURPOSE: To compare vision-related quality of life in implantable Collamer lens
      (ICL) recipients and successful contact lens (CL) wearers not seeking refractive
      surgery. DESIGN: A comparative cross-sectional study of consecutive cases.
      PARTICIPANTS: Forty-one consecutive cases of bilateral ICL implantation in
      Moorfields Eye Hospital, London, and a control group of 41 CL wearers with a
      similar starting level of myopia attending consecutively at 1 of 2 community
      optometric practices in the London area. INTERVENTION: Quality of Life Impact of
      Refractive Correction questionnaire administration in a semistructured interview.
      MAIN OUTCOME MEASURE: Quality of Life Impact of Refractive Correction score.
      RESULTS: Quality of Life Impact of Refractive Correction scores were
      significantly higher (P<0.001) in ICL recipients (53.67+/-4.50) than in CL
      wearers (44.42+/-5.07). Age (mean+/-standard deviation [SD], 37.7+/-7 vs. 37.5+/
      7.3), gender distribution (% female, 90% vs. 74%; P = 0.295), and preoperative
      (ICL recipients) or uncorrected (CL wearers) refractive error (mean refractive
      spherical equivalent+/-SD, 11.0+/-2.7 vs. 11.3+/-3.5) were similar in ICL
      recipients and CL wearers, respectively. Postoperative uncorrected visual
      acuities in ICL recipients (0.04 [20/20]+/-0.18) and CL-corrected visual acuities
      in control patients (0.01 [20/20]+/-0.14) measured in the better eye in each
      group also were similar (P = 0.53). CONCLUSIONS: Implantable Collamer lens
      implantation may offer significant quality-of-life advantages over CL wear for
      patients with high myopia. FINANCIAL DISCLOSURE(S): The author(s) have no
      proprietary or commercial interest in any materials discussed in this article.

PMID- 19091408
TI  - Applying the CONSORT and STROBE statements to evaluate the reporting quality of
      neovascular age-related macular degeneration studies.
AB  - PURPOSE: To evaluate the quality of reporting in the neovascular age-related
      macular degeneration (nvAMD) literature by applying the Consolidated Standards
      for Reporting Trials (CONSORT) and Strengthening the Reporting of Observational
      Studies in Epidemiology (STROBE) statement writing standards. DESIGN: CONSORT and
      STROBE impact analysis; literature review. PARTICIPANTS: Phase III randomized
      controlled trials (RCTs) of verteporfin photodynamic therapy, pegaptanib, and
      ranibizumab, and interventional case studies of bevacizumab for nvAMD. METHODS: A
      literature search identified eligible articles published before October 31, 2007.
      We assessed the report quality of Phase III RCTs using the CONSORT statement and
      case series publications using the STROBE statement, both with indicators
      relevant to nvAMD. MAIN OUTCOME MEASURES: Presence or absence of CONSORT or
      STROBE statement indicators. RESULTS: Seven publications of Phase III RCTs and 29
      publications on bevacizumab interventional case studies for nvAMD met our
      inclusion criteria. Of 37 possible CONSORT writing guideline items, the mean
      report quality for RCTs was 30.6 (83%), with a range from 23 to 35 (65%-95%). Of
      35 possible STROBE writing guideline items, the mean report quality grade for
      intravitreal bevacizumab case series was 23 (70%), with a range from 16 to 31
      (46%-94%). Among the bevacizumab studies, more than 90% reported scientific
      background, drug dose and administration, baseline characteristics, unadjusted
      results, and adverse events. Fewer than 20% reported study size calculations,
      handling of missing data, or a discussion of bias. CONCLUSIONS: Since the
      adoption of the CONSORT standards by Ophthalmology and other journals in 1996,
      the reporting quality for RCTs has further improved among this cohort of nvAMD
      articles. On the other hand, no reporting standards for case series have existed
      until the recent publication of the STROBE statement. In this first application
      of the STROBE standards to ophthalmology, we found that the small interventional
      studies in our series had an average reporting score lower than the RCTs, but
      also that some individual scores were higher than the RCTs. This outcome
      demonstrates that good, useful articles can be written about small studies.
      Although not a direct measure of the quality of a study, good reporting allows a
      reader to assess the validity and applicability of the study's findings.
      FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found after
      the references.

PMID- 19091409
TI  - Astigmatism in the Early Treatment for Retinopathy Of Prematurity Study: findings
      to 3 years of age.
AB  - PURPOSE: To examine the prevalence of astigmatism (> or =1.00 diopter [D]) and
      high astigmatism (> or =2.00 D) at 6 and 9 months corrected age and 2 and 3 years
      postnatal age, in preterm children with birth weight of less than 1251 g in whom
      high-risk prethreshold retinopathy of prematurity (ROP) developed and who
      participated in the Early Treatment for Retinopathy of Prematurity (ETROP) Study.
      DESIGN: Randomized, controlled clinical trial. PARTICIPANTS: Four hundred one
      infants in whom prethreshold ROP developed in one or both eyes and who were
      randomized after they were determined to have a high risk (> or =15%) of poor
      structural outcome without treatment using the Risk Management of Retinopathy of
      Prematurity (RM-ROP2) program. Refractive error was measured by cycloplegic
      retinoscopy. Eyes with additional retinal, glaucoma, or cataract surgery were
      excluded. INTERVENTION: Eyes were randomized to receive laser photocoagulation at
      high-risk prethreshold ROP (early treated [ET]) or to be conventionally managed
      (CM), receiving treatment only if threshold ROP developed. MAIN OUTCOME MEASURES:
      Astigmatism and high astigmatism at each visit. Astigmatism was classified as
      with-the-rule (WTR; 75 degrees -105 degrees ), against-the-rule (ATR; 0 degrees 
      15 degrees and 165 degrees -180 degrees ), or oblique (OBL; 16 degrees -74
      degrees and 106 degrees -164 degrees ). RESULTS: The prevalence of astigmatism in
      ET and CM eyes was similar at each test age. For both groups, there was an
      increase in prevalence of astigmatism from approximately 32% at 6 months to
      approximately 42% by 3 years, mostly occurring between 6 and 9 months. Among eyes
      that could be refracted, astigmatism was not influenced by zone of acute-phase
      ROP, presence of plus disease, or retinal residua of ROP. Eyes with astigmatism
      and high astigmatism most often had WTR astigmatism. CONCLUSIONS: By age 3 years,
      nearly 43% of eyes treated at high-risk prethreshold ROP developed astigmatism of
      > or =1.00 D and nearly 20% had astigmatism of > or =2.00 D. Presence of
      astigmatism was not influenced by timing of treatment of acute-phase ROP or by
      characteristics of acute-phase or cicatricial ROP. These findings reinforce the
      need for follow-up eye examinations in infants with high-risk prethreshold ROP.
      FINANCIAL DISCLOSURE(S): The author(s) have no proprietary or commercial interest
      in any materials discussed in this article.

PMID- 19091410
TI  - Defining real change in measures of stereoacuity.
AB  - PURPOSE: To establish the thresholds for "real change" in stereoacuity by
      defining long-term test-retest variability as 95% limits of agreement for 4
      stereoacuity tests. DESIGN: Retrospective cohort study. PARTICIPANTS AND
      CONTROLS: We identified 36 patients (median, 17 years; range, 7-76) with any type
      of stable strabismus who had stereoacuity measured on 2 consecutive visits.
      Stable strabismus was defined as angle of deviation within 5 prism diopters by
      simultaneous prism and cover test and prism and alternating cover test. METHODS:
      Stereoacuity was measured at near using the preschool Randot and the near Frisby
      stereotests and at distance using the Frisby-Davis distance (FD2) and the
      distance Randot stereotests. Stereoacuity was transformed to log units for
      analysis. The 95% limits of agreement were calculated based on a 1.96 multiple of
      the standard deviation of differences between test and retest. MAIN OUTCOME
      MEASURES: The 95% limits of agreement for change in stereoacuity thresholds at 2
      consecutive visits. RESULTS: The 95% limits of agreement were 0.59 log arcsec for
      the preschool Randot, 0.24 for the near Frisby, 0.68 for the FD2, and 0.46 for
      the distance Randot. These values correspond with the following octave steps
      (doublings of threshold; e.g., 200-400 arcsec): preschool Randot, 1.95; near
      Frisby, 0.78; FD2, 2.27; and distance Randot, 1.52. CONCLUSIONS: A change of
      approximately 2 octaves of stereoacuity threshold are needed to exceed test
      retest variability for most stereoacuity tests. Changes <2 octaves cannot be
      distinguished from test-retest variability. When used to guide patient
      management, caution should be taken in interpreting changes in stereoacuity of <2
      octaves. FINANCIAL DISCLOSURE(S): The authors have no proprietary or commercial
      interest in any materials discussed in this article.

PMID- 19091411
TI  - Skills acquisition and assessment after a microsurgical skills course for
      ophthalmology residents.
AB  - OBJECTIVE: To assess the impact of a skills course on microsurgical skills
      acquisition and to investigate the validity of a video-based modified Objective
      Structured Assessment of Technical Skill (OSATS) assessment tool that has not
      previously been applied to ophthalmic surgery. DESIGN: Prospective longitudinal
      cohort study. PARTICIPANTS: Fourteen residents were recruited from 20 attendees
      at the Moorfields Eye Hospital microsurgical skills course for residents.
      METHODS: Each resident performed a standardized microsurgical task consisting of
      the placement of a 10-0 nylon corneal suture into a model eye using an operating
      microscope with standardized equipment in a standardized environment. Objective
      measurements were made using the Imperial College Surgical Assessment Device
      (ICSAD). This is a motion-tracking device returning 3 parameters for economy of
      movement: total path length, time, and number of individual hand movements. A
      concurrent video recording was made of each task by 2 independent observers who
      were masked to the time of the recording relative to the course and the identity
      of the resident. Video footage was marked in accordance with the OSATS video
      scoring template. MAIN OUTCOME MEASURES: Each resident had motion-tracking
      analysis performed during corneal suturing before and after the course (total
      path length, time, and number of individual hand movements), along with
      concurrent OSATS video scores. RESULTS: Skills improvement after the course was
      found to be statistically significant for all 3 ICSAD economy of movement
      parameters: path length, P = 0.001; hand movements, P = 0.012; and time, P =
      0.009. Differences in the combined OSATS scores of the 2 raters before and after
      the course were found to be significant (P = 0.039). Interrater reliability of
      OSATS scorers was 0.78 (alpha Cronbach). Correlations between the OSATS scores
      and each of the ICSAD parameters were found to be significant (P<0.001).
      CONCLUSIONS: A video-based OSATS scoring system has significant correlation with
      the ICSAD motion-tracking parameters, demonstrating concurrent validity between
      the 2 assessment tools. These data also demonstrate that surgical skill, as
      measured by a validated motion-tracking system, is significantly improved after a
      1-day microsurgical skills course. FINANCIAL DISCLOSURE(S): The author(s) have no
      proprietary or commercial interest in any materials discussed in this article.

PMID- 19091412
TI  - Clinical and histopathologic review of 18 explanted porous polyethylene orbital
      implants.
AB  - PURPOSE: To review the clinical and histopathologic features of porous
      polyethylene (PP) orbital implants requiring explantation. DESIGN: Case series.
      PARTICIPANTS: Eighteen explanted PP orbital implants of 18 patients were studied.
      METHODS: The charts and histopathologic findings were reviewed for all patients
      requiring explantation of PP orbital implants between 1997 and 2006 by 2
      oculoplastic surgeons at the University of British Columbia. MAIN OUTCOME
      MEASURES: Clinical data obtained included patient demographics, the nature of the
      primary surgery, and the clinical presentation leading to eventual implant
      removal. The histopathologic data observed included the presence of anterior
      exposure, area of fibrovascular ingrowth, type of inflammation, and presence and
      type of bacterial colonies. RESULTS: Nine (50%) of the 18 patients studied were
      referred from other surgeons. The balance represented 3.2% of all PP implants
      placed by the 2 surgeons. The procedures for the primary surgery were 12
      enucleations (67%), 5 eviscerations (28%), and 1 secondary implant (5%). Clinical
      findings included anterior implant exposure and discharge in all cases.
      Histopathologic analysis was performed in all of the implants and showed less
      than 50% fibrovascular ingrowth in 16 implants (89%) and predominantly acute or
      mixed inflammation in 15 (83%). Foreign body giant cells were seen adjacent to
      the implant material in all cases. Bacterial colonies on gram stain were
      identified in 12 specimens (67%); overall, gram-positive cocci in clusters or
      chains were found in 10 implants (56%), and gram-negative bacteria were found in
      1 (5.5%). Thirteen patients (72%) lived in locations distant from Vancouver, the
      surgical center. CONCLUSIONS: This article presents the largest review of
      explanted porous polyethylene orbital spheres. The findings suggest that anterior
      exposure allows bacterial colonization and the development of a heavy
      inflammatory infiltrate. Poor tissue ingrowth may limit the penetration of
      topical or systemic antibiotic therapy, leading to the necessity for
      explantation. FINANCIAL DISCLOSURE(S): The author(s) have no proprietary or
      commercial interest in any materials discussed in this article.

PMID- 19091413
TI  - Three-dimensional high-speed optical coherence tomography imaging of lamina
      cribrosa in glaucoma.
AB  - OBJECTIVE: To evaluate the appearance of the optic nerve head and lamina cribrosa
      in patients with glaucoma using spectral/Fourier-domain optical coherence
      tomography (SD-OCT) and to test for a correlation between lamina cribrosa
      thickness measured on SD-OCT images and visual field loss. DESIGN: Observational
      case series. PARTICIPANTS: We evaluated 52 eyes of 30 patients with glaucoma or
      ocular hypertension. METHODS: The high-speed SD-OCT equipment used was a
      prototype system developed for 3-dimensional (3D) imaging. It had a sensitivity
      of 98 decibels (dB), a tissue axial resolution of 4.3 mum, and an acquisition
      rate of approximately 18,700 axial scans per second. For 3D analyses, a raster
      scan protocol of 256 x 256 axial scans covering a 2.8 x 2.8 mm disc area was
      used. Lamina cribrosa thickness was measured on 3D images using 3D image
      processing software. Correlation between lamina cribrosa thickness and mean
      deviation (MD) values obtained using static automatic perimetry were tested for
      statistical significance. MAIN OUTCOME MEASURES: Clarity of lamina cribrosa
      features, lamina cribrosa thickness, and MD values on static automatic perimetry.
      RESULTS: On 3D images, the lamina cribrosa appeared clearly as a highly
      reflective plate that was bowed posteriorly and contained many circular areas of
      low reflectivity. The dots of low reflectivity visible just beneath the anterior
      surface of the lamina cribrosa in en face cross-sections corresponded with dots
      representing lamina pores in color fundus photographs. The mean (+/-1 standard
      deviation) thickness of the lamina cribrosa was 190.5+/-52.7 mum (range, 80.5
      329.0). Spearman rank testing and linear regression analysis showed that lamina
      cribrosa thickness correlated significantly with MD (Spearman sigma = 0.744;
      P<0.001; r(2) = 0.493; P<0.001). Different observers performed measurements of
      the lamina cribrosa thickness in SD-OCT cross-sectional images with high
      reproducibility (intraclass correlation coefficient = 0.784). CONCLUSIONS: These
      3D SD-OCT imaging clearly demonstrated the 3D structure of the lamina cribrosa
      and allowed measurement of its thickness, which correlated significantly with
      visual field loss, in living patients with glaucoma. This noninvasive imaging
      technique should facilitate investigations of structural changes in the optic
      nerve head lamina cribrosa in eyes with optic nerve damage due to glaucoma.
      FINANCIAL DISCLOSURE(S): The authors have no proprietary or commercial interest
      in any materials discussed in this article.

PMID- 19091414
TI  - Precut tissue for Descemet's stripping automated endothelial keratoplasty:
      vision, astigmatism, and endothelial survival.
AB  - PURPOSE: To report 6 and 12 month results using precut tissue for Descemet's
      stripping automated endothelial keratoplasty (DSAEK) and correlate donor
      characteristics with clinical outcomes. DESIGN: Prospective, noncomparative,
      interventional case series. PARTICIPANTS: We reviewed 100 donor corneas precut
      for 100 eyes of 90 DSAEK patients. METHODS: Our first 100 consecutive cases of
      DSAEK with precut tissue were entered into a prospective protocol. Donor
      characteristics and the visual, refractive, topographic, and specular microscopy
      results at 6 and 12 months were analyzed. Correlation analysis comparing donor
      characteristics with clinical outcomes was performed. MAIN OUTCOME MEASURES: Six-
      and 12-month postoperative best spectacle-corrected visual acuity (BSCVA),
      refractive astigmatism, topographic keratometry (K), and specular endothelial
      cell densities (ECD) were measured prospectively and then compared with
      preoperative values. Donor characteristics analyzed included death to
      preservation time, death to surgery time, precutting resection to surgery time,
      and graft thickness. RESULTS: Six months after DSAEK surgery, BSCVA improved from
      20/83 to 20/38. (P<0.01). In eyes with no known comorbidity (n = 60), 92% had a
      vision of >/=20/40 at 6 months and 20% obtained > or =20/20. Astigmatism changed
      an average of 0.09 diopters (D) and K changed by +0.09 D, both of which were not
      significant and were stable to 12 months. The postoperative mean ECD (n = 65) was
      1918 cells/mm(2) at 6 months, and represented a 31% cell loss from preoperatively
      (P<0.001). The mean ECD (n = 61) was 1990 cells/mm(2) at 12 months, and
      represented a 29% cell loss from preoperatively (P<0.001) with no significant
      change from 6 to 12 months (P = 0.172). Improvement of visual acuity from
      preoperative to postoperative in eyes without comorbidity was not correlated with
      any donor characteristic. Greater endothelial cell loss correlated with higher
      preoperative ECD levels (P<0.001) and with a trend toward longer precut resection
      to surgery times at both 6 months (P = 0.049) and 12 months (P = 0.051).
      CONCLUSIONS: Precut tissue by Eye Banks for use in DSAEK surgery provides an
      improvement in vision with no significant change in astigmatism. Donor
      endothelial cell loss from 6 to 12 months is stable and is comparable with
      reports involving tissue that is cut intraoperatively. FINANCIAL DISCLOSURE(S):
      Proprietary or commercial disclosures may be found after the references.

PMID- 19091415
TI  - Constant ocular infection with Chlamydia trachomatis predicts risk of scarring in
      children in Tanzania.
AB  - OBJECTIVE: Clinically, constant severe trachoma predicts an increased risk of
      scarring in children. There are no data on the risk of scarring associated with
      constant infection with Chlamydia trachomatis, regardless of clinical
      manifestation. We propose to determine the 5-year incidence of scarring in
      children with a history of constant severe trachoma, constant infection, or both
      compared with children who had a history of neither. DESIGN: A 5-year,
      longitudinal observational study. PARTICIPANTS: Children aged less than 10 years
      with data on trachoma and infection for 3 of the 5 visits in the first 18 months,
      and follow-up 5-year data on scarring. METHODS: Data were collected on clinical
      trachoma, and ocular swabs were taken to determine the presence of C. trachomatis
      in children in a hyperendemic village in Tanzania. Images were graded for
      scarring. Data were collected at baseline; 2, 6, 12, and 18 months; and 5 years
      from baseline. Severe trachoma was defined as the presence of 10 or more
      follicles, or trachoma intense. A child had constant infection (severe trachoma)
      if infection (severe trachoma) was present on at least 3 visits before the 5-year
      survey. MAIN OUTCOME MEASURES: Five-year risk of scarring. RESULTS: Of the 189
      children, 22 (11.6%) had constant severe trachoma, but not constant infection.
      Nine children (4.8%) had constant infection but not constant severe trachoma.
      Both constant severe trachoma and constant infection were present in 16 children
      (8.5%). The 5-year incidence of scarring was similar in all 3 groups; children
      with constant severe trachoma only, with constant infection only, and with both
      were most likely to develop scars (35.0%, 44.4%, 31.2%, respectively) compared
      with those with sporadic trachoma or infection (15.2%) or neither (6.8%) (P =
      0.0002). CONCLUSIONS: Children with constant infection are also likely to have
      constant severe trachoma, and their 5-year risk of scarring is high compared with
      children with sporadic severe trachoma or infection. These data further support
      the presence of a subgroup of children who cannot clear infection with C.
      trachomatis, who may manifest a severe immunologic response to infection, and who
      are at increased risk of scarring sequelae. FINANCIAL DISCLOSURE(S): Proprietary
      or commercial disclosure may be found after the references.

PMID- 19091416
TI  - Visual impairment and vision-related quality of life in working-age adults:
      findings in the 1958 British birth cohort.
AB  - PURPOSE: To describe the prevalence of impaired vision and its relative burden,
      together with the prevalence of impaired vision-related quality of life (VRQOL),
      and investigate associations with social outcomes in a contemporary and
      nationally representative population of working age adults. DESIGN: Population
      based cross-sectional study. PARTICIPANTS: We included 9330 members of the 1958
      British birth cohort at age 44 and 45 years. METHODS: "Habitual" and "best
      achieved" distance visual acuity in each eye, binocular near vision acuity and
      stereoacuity (three dimensional/depth perception) were tested during a broader
      biomedical examination. VRQOL was assessed using the Vision-related Quality of
      Life Core Measure 1 (VCM1), a validated, 10-item, self-complete instrument.
      Logistic and proportional odds ordinal logistic regression were used to calculate
      odds ratios (ORs) of the association of VRQOL with visual acuities and social
      outcomes. MAIN OUTCOME MEASURES: Distance, near, and stereo acuities and VRQOL
      and social outcomes. RESULTS: Of the 1.3% (124) of those with visual loss that
      precluded driving, a further 0.75% (70) were visually impaired or severely
      visually impaired and 0.15% (14) blind, the latter accounting for 19% total
      population (all ages) burden of blindness. Impairment of VRQOL is strongly
      associated with impaired distance, near, and stereo vision, as well as with
      adverse occupational and other social outcomes. However, VRQOL impairment is also
      sometimes reported with unilateral or mild bilateral visual loss. CONCLUSIONS:
      Although impaired vision in working age adults is relatively uncommon, it confers
      important adverse consequences for the "health and wealth" of the public. This
      may be captured best by assessment of VRQOL in addition to objective visual
      function. Ophthalmic disorders occurring or impacting in middle life should be
      given a higher priority than currently in national and international strategies
      against avoidable visual disability. FINANCIAL DISCLOSURE(S): Proprietary or
      commercial disclosure may be found after the references.

PMID- 19091417
TI  - Risk factors for acute endophthalmitis after cataract surgery: a population-based
      study.
AB  - OBJECTIVE: To identify risk factors for suspected acute endophthalmitis after
      cataract surgery. DESIGN: Population-based retrospective cohort. PARTICIPANTS:
      Administrative data from more than 440,000 consecutive cataract surgeries in
      Ontario, Canada, from April 1, 2002, to March 31, 2006. METHODS: Consecutive
      physician billing claims for cataract surgery and specific intraoperative and
      postoperative procedures related to complications of cataract surgery were
      identified. Acute endophthalmitis was defined using surrogate markers for
      intraocular infection, including vitrectomy, vitreous injection, or aspiration
      procedures not in combination with air/fluid exchange or dislocated lens
      extraction, performed 1 to 14 days after cataract surgery. Anterior vitrectomy
      performed on the day of surgery was used as a surrogate marker for capsular
      rupture. MAIN OUTCOME MEASURES: Overall rates of endophthalmitis were calculated
      and grouped by patient demographics, surgical facility, season, year, and
      association with capsular rupture. RESULTS: There were 617 suspected acute
      endophthalmitis cases of 442,177 cataract surgeries over the 4 years. The overall
      unadjusted and adjusted rates of suspected acute endophthalmitis were both 1.4
      per 1000 cataract surgeries. Men had higher rates than women (1.70 vs. 1.19/1000
      surgeries, P<0.0001) with an adjusted odds ratio of 1.40 (95% confidence
      interval, 1.19-1.64).The oldest age group (>or= 85 years) had the highest rate
      (2.18/1000), and the youngest group (20-64) had the second highest rate
      (1.76/1000). The endophthalmitis rates for these age groups were significantly
      different from those aged 65 to 84 years. The endophthalmitis rate was
      approximately 10-fold higher in those with capsular rupture compared with those
      without (13.11 vs. 1.34/1000, P<0.0001), with an adjusted odds ratio of 9.56 (95%
      confidence interval, 6.43-14.2). CONCLUSIONS: The overall rates of suspected
      acute endophthalmitis are low but significantly higher in certain patient groups.
      Our population-based analysis can be used as a benchmark for quality-improvement
      initiatives and can assist clinicians in educating their patients regarding the
      risks associated with cataract surgery. Future work is required to address the
      higher rate of endophthalmitis in men, those with capsular rupture, and the
      oldest patients undergoing cataract surgery.

PMID- 19091418
TI  - Positive interaction between light iris color and ultraviolet radiation in
      relation to the risk of uveal melanoma: a case-control study.
AB  - PURPOSE: To examine the association among phenotypic characteristics, chronic and
      intermittent ultraviolet (UV) radiation, and the risk of uveal melanoma. DESIGN:
      Case-control study. PARTICIPANTS: Overall, between September of 2002 and March of
      2005, 1677 eligible subjects (age range: 20-74 years, living in Germany)
      participated. Interviews were conducted with 459 incident uveal melanoma cases
      (response proportion 94%), 827 population controls (55%), 180 ophthalmologist
      controls (52%), and 187 sibling controls (57%). METHODS: Data on phenotypic
      characteristics and chronic and intermittent UV radiation exposure were obtained
      from a self-administered postal questionnaire and computer-assisted telephone
      interview. We used conditional logistic regression to estimate odds ratios
      adjusting for the matching factors. Furthermore, we studied the presence of
      synergy (super additive of risk or relative excess risk due to interaction)
      between light iris color and several UV radiation exposures. MAIN OUTCOME
      MEASURES: Hair color at age 20 years, eye color, untanned skin color, ability to
      tan, propensity to burn on exposure, freckling, occupational sun exposure,
      artificial UV radiation, burns to the eyes. RESULTS: In all 3 control groups,
      fair skin color, freckling as a child, nevi on the upper arms, burns to the eyes,
      use of sunlamps, and ever worked outside for 4 or more hours per day were
      positively associated with uveal melanoma. The association with eye color was
      apparent only in population controls (odds ratio = 1.9; 95% confidence interval
      [CI], 1.4-5.2), resulting in a relative excess risk due to interaction of 0.9
      (95% CI, -0.6-2.3) for light iris color and more than 5 eye burns (UV-related
      keratitis) and 0.6 (95% CI, -0.3 to 1.5) for light iris color and eye protection.
      CONCLUSIONS: Our interaction analyses suggest that there is an etiologic
      synergism between light iris color and the exposure of UV radiation. People with
      light iris color may have an especially increased risk for uveal melanoma if they
      are exposed to UV radiation. FINANCIAL DISCLOSURE(S): The author(s) have no
      proprietary or commercial interest in any materials discussed in this article.

PMID- 19091419
TI  - Adnexal surgery in patients undergoing ocular surface stem cell transplantation.
AB  - PURPOSE: To examine the role of adnexal disease and surgery in the outcome of
      ocular surface stem cell transplantation. DESIGN: Retrospective, noncomparative
      case series. PARTICIPANTS: Twenty-two patients (23 eyes) with severe corneal stem
      cell deficiency undergoing ocular surface stem cell transplantation. METHODS:
      Consecutive cases of stem cell grafting for ocular surface disease over a 6-year
      period at a single institution were studied. MAIN OUTCOME MEASURES: Main outcome
      measures were 2-fold: (1) nature of eyelid, fornix, and lacrimal abnormalities
      encountered; indications for treatment; methods; and outcome of adnexal surgery;
      (2) stem cell allograft success with respect to underlying disease, indication
      for stem cell grafting, preoperative adnexal involvement, and adnexal surgery
      after stem cell grafting. RESULTS: Twenty-nine limbal stem cell grafts on 23 eyes
      of 22 patients were identified during the study. Seventeen ex vivo expanded stem
      cell allografts, 11 keratolimbal allografts, and 1 living-related donor limbal
      allograft were performed, with combined stem cell techniques used in 5 patients.
      Median follow-up was 26.5 months (standard deviation, 18.6 months). Overall, stem
      cell graft success at final review was 69%. Thirty-four percent (10/29) of cases
      had eyelid involvement and 41% (12/29) had fornix involvement at the time of stem
      cell grafting. Trichiasis and symblepharon were the most common abnormalities.
      Fornix involvement was associated with a 50% chance of stem cell graft failure.
      After stem cell grafting, 66% (19/29) of cases required adnexal surgery. This was
      for lagophthalmos in 11 cases (46%), eyelid malposition in 7 cases (23%), fornix
      shortening in 5 cases (19%), and punctal patency in 8 cases (31%). Punctal
      patency and lagophthalmos frequently required repeated procedures for successful
      correction. Epithelial healing promptly followed correction of the adnexal
      abnormality with surgery; however, the need for adnexal surgery was associated
      with a 50% chance of stem cell graft failure. CONCLUSIONS: Concurrent adnexal
      abnormalities are associated with worse graft outcomes after stem cell
      transplantation and can compromise epithelial healing if uncorrected. Surgery for
      eyelid malposition and closure is essential before and after transplantation for
      surface epithelial integrity and often requires multiple procedures. FINANCIAL
      DISCLOSURE(S): The author(s) have no proprietary or commercial interest in any
      materials discussed in this article.

PMID- 19091421
TI  - Combined chelation of bi-functional bis-hydroxypiridinone and mono
      hydroxypiridinone: synthesis, solution and in vivo evaluation.
AB  - 3-Hydroxy-4-pyridinones (3,4-HP) are well known iron-chelators with applications
      in medicinal chemistry, mainly associated with their high affinity towards
      trivalent hard metal ions (e.g. M(3+), M=Fe, Al, Ga) and use as decorporating
      agents in situations of metal accumulation. The polydenticity and the extra
      functionality of 3,4-HP derivatives have been explored, aimed at improving the
      chelating efficacy and the selectivity of the interaction with specific
      biological receptors. However, the ideal conjugation of both features in one
      molecular unity usually leads to high molecular weight compounds which can have
      crossing-membrane limitations. Herein, a different approach is used combining a
      arylpiperazine-containing bis-hydroxypyridone (H(2)L(1)) with a biomimetic mono
      hydroxypyridinone, ornithine-derivative (HL(2)), to assess the potential
      coadjuvating effect that could result from the administration of both compounds
      for the decorporation of hard metal ions. This work reports the results of
      solution and in vivo studies on their chelating efficacy either as a simple
      binary or a ternary system (H(2)L(1):HL(2):M(3+)), using potentiometric and
      spectrophotometric methods. The solution complexation studies with Fe(III)
      indicate that the solubility of the complexes is considerably increased in the
      ternary system, an important feature for the metal complex excretion, upon the
      metal sequestration. The results of the in vivo studies with (67)Ga-injected mice
      show differences on the biodistribution profiles of the radiotracer, upon the
      administration of each chelating agent, that are mainly ascribed to the
      differences of their extra-functional groups and lipo/hydrophilic character.
      However, administration of both chelating agents leads to a more steady metal
      mobilization, which may be attributed to an improved access to different cellular
      compartments.

PMID- 19091420
TI  - Risk of advanced age-related macular degeneration after cataract surgery in the
      Age-Related Eye Disease Study: AREDS report 25.
AB  - PURPOSE: To assess the risk of advanced age-related macular degeneration (AMD)
      developing after cataract surgery. DESIGN: Cohort study. PARTICIPANTS: Four
      thousand five hundred seventy-seven participants (8050 eyes) from a multicenter,
      controlled, randomized clinical trial, the Age-Related Eye Disease Study (AREDS).
      METHODS: Development of advanced AMD, either neovascular (NV) AMD or geographic
      atrophy (GA), was evaluated with annual fundus photographs, and history of
      cataract surgery was assessed every 6 months. Cox proportional hazard models with
      time-dependent covariates were conducted for NV AMD and GA separately. MAIN
      OUTCOME MEASURES: Neovascular AMD, GA, and central GA (CGA; involving the center
      of the macula). RESULTS: The Cox proportional hazards model of right eyes showed
      nonsignificant hazard ratios of 1.20 (95% confidence interval [CI], 0.82-1.75)
      for NV AMD, 0.80 (95% CI, 0.61-1.06) for GA, and 0.87 (95% CI, 0.64-1.18) for
      CGA. Similar results were obtained for left eyes: 1.07 (95% CI, 0.72-1.58) for NV
      AMD, 0.94 (95% CI, 0.71-1.25) for GA, and 0.86 (95% CI, 0.63-1.19) for CGA. For
      participants with advanced AMD in 1 eye (AREDS category 4), the hazard ratios for
      fellow eyes were 1.08 (95% CI, 0.65-1.72) for NV AMD and 0.98 (95% CI, 0.64-1.49)
      for CGA. CONCLUSIONS: The AREDS results showed no clear effect of cataract
      surgery on the risk of progression to advanced AMD. FINANCIAL DISCLOSURE(S): The
      author(s) have no proprietary or commercial interest in any materials discussed
      in this article.

PMID- 19091422
TI  - Design of vanadium mixed-ligand complexes as potential anti-protozoa agents.
AB  - In the search for new therapeutic tools against Chagas' disease (American
      Trypanosomiasis) four novel mixed-ligand vanadyl complexes, [V(IV)O(L(2)
      2H)(L(1))], including a bidentate polypyridyl DNA intercalator (L(1)) and a
      tridentate salycylaldehyde semicarbazone derivative (L(2)) as ligands were
      synthesized, characterized by a combination of techniques, and in vitro
      evaluated. EPR suggest a distorted octahedral geometry with the tridentate
      semicarbazone occupying three equatorial positions and the polypyridyl ligand
      coordinated in an equatorial/axial mode. Both complexes including dipyrido[3,2-a:
      2',3'-c]phenazine (dppz) as polypyridyl coligand showed IC(50) values in the muM
      range against Dm28c strain (epimastigotes) of Trypanosoma cruzi, causative agent
      of the disease, being as active as the anti-trypanosomal reference drug
      Nifurtimox. To get an insight into the trypanocidal mechanism of action of these
      compounds, DNA was evaluated as a potential parasite target and EPR, and (51)V
      NMR experiments were also carried out upon aging aerated solutions of the
      complexes. Data obtained by electrophoretic analysis suggest that the mechanism
      of action of these complexes could include DNA interactions.

PMID- 19091423
TI  - Relative chemokine and adhesion molecule expression in Mediterranean spotted
      fever and African tick bite fever.
AB  - OBJECTIVES: Mediterranean spotted fever (MSF) caused by Rickettsia conorii (R.
      conorii) is a potential lethal disease while African tick bite fever (ATBF)
      caused by Rickettsia africae is a self-limiting flu-like illness. We hypothesized
      that different inflammatory potential in endothelial cells could contribute to
      the different clinical features in these rickettsioses. METHODS: We analyzed the
      effect of heat-inactivated R. africae and R. conorii on the mRNA and protein
      levels of monocyte chemoattractant protein (MCP)-1, interleukin (IL)-8 and
      adhesion molecules in endothelial cells. Serum samples from patients with MSF
      (n=16) and ATBF (n=15) were collected before and after therapy. RESULTS: R.
      conorii induced a marked increase in MCP-1, IL-8, and adhesion molecules in
      endothelial cells, involving toll-like receptor 4 activation. In contrast, R.
      africae induced MCP-1 expression, but only modest or no responses were seen on IL
      8 and adhesion molecules. Comparable to the in vitro response, levels of IL-8 and
      adhesion molecules showed no or only a modest increase in ATBF patients while
      these inflammatory markers were markedly elevated during MSF. CONCLUSIONS: Our
      findings suggest a superior inflammatory potential of R. conorii as compared to
      R. africae in endothelial cells, potentially related to the more severe
      inflammation in MSF comparing ATBF.

PMID- 19091425
TI  - The role of leukocyte biology in laminitis.
AB  - The underlying pathogenesis of laminitis clearly depends importantly on
      inflammatory processes that recruit leukocytes at an early stage in disease. The
      role of leukocytes in the initiation of laminitis, or as an intermediary factor
      is currently being investigated using a limited array of models, and future
      studies require both new reagent and model systems if we are to clearly define
      how leukocytes propagate this disease. The opportunities presented by this type
      of research could easily include new and powerful treatment and preventative
      modalities.

PMID- 19091424
TI  - Relationship among latitude, climate, season and self-reported mood in bipolar
      disorder.
AB  - OBJECTIVE: Many researchers have analyzed seasonal variation in hospital
      admissions for bipolar disorder with inconsistent results. We investigated if a
      seasonal pattern was present in daily self-reported daily mood ratings from
      patients living in five climate zones in the northern and southern hemispheres.
      We also investigated the influence of latitude and seasonal climate variables on
      mood. METHOD: 360 patients who were receiving treatment as usual recorded mood
      daily (59,422 total days of data). Both the percentage of days depressed and
      hypomanic/manic, and the episodes of depression and mania were determined. The
      observations were provided by patients from different geographic locations in
      North and South America, Europe and Australia. These data were analyzed for
      seasonality by climate zone using both a sinusoidal regression and the Gini
      index. Additionally, the influence of latitude and climate variables on mood was
      estimated using generalized linear models for each season and month. RESULTS: No
      seasonality was found in any climate zone by either method. In spite of vastly
      different weather, neither latitude nor climate variables were associated with
      mood by season or month. CONCLUSION: Daily self-reported mood ratings of most
      patients with bipolar disorder did not show a seasonal pattern. Neither climate
      nor latitude has a primary influence on the daily mood changes of most patients
      receiving medication for bipolar disorder.

PMID- 19091426
TI  - Plasma concentrations of endotoxin and platelet activation in the developmental
      stage of oligofructose-induced laminitis.
AB  - The link between the fermentation of carbohydrate in the equine large intestine
      and the development of acute laminitis is poorly understood. Absorption of
      endotoxin (lipopolysaccharide; LPS) into the plasma has been observed in one
      experimental model of laminitis, but does not cause laminitis when administered
      alone. Thus, the potential role of endotoxin is unclear. Platelet activation has
      previously been demonstrated in the developmental stage of laminitis. Equine
      platelets are more sensitive than leukocytes to activation by endotoxin, and can
      be activated directly by LPS in the low pg/ml range, activating p38 MAP kinase
      and releasing serotonin (5-HT) and thromboxane. The objectives of this study were
      firstly to determine whether endotoxin and platelet activation could be measured
      in the plasma of horses in the developmental phase of laminitis induced with
      oligofructose. Secondly, the time course of events involving platelet activation
      and platelet-derived vasoactive mediator production was investigated. Laminitis
      was induced in six Standardbred horses by the administration of 10 g/kg bwt of
      oligofructose. Plasma samples were obtained every 4h, and platelet pellets were
      obtained by centrifugation. LPS was measured using a kinetic limulus amebocyte
      lysate assay, and platelet activation was assessed by Western blotting for the
      phosphorylated form of p38 MAP kinase. Plasma 5-HT was assayed by HPLC with
      electrochemical detection and thromboxane B(2) was measured by radioimmunoassay.
      Clinical signs of laminitis and histopathologic changes were observed in lamellar
      sections from five of the six horses. Onset of lameness was between 20 and 30 h
      after the administration of oligofructose. LPS increased above the limit of
      detection (0.6 pg/ml) to reach a peak of 2.4+/-1.0 pg/ml at 8 h. TNFalpha was
      also detectable in the plasma from 12 to 24 h. There was a time-dependent
      increase in platelet p38 MAPK phosphorylation, which peaked at approximately 12 h
      (3.8+/-1.3 fold increase); plasma 5-HT and thromboxane increased steadily after
      this time (2.9+/-0.6 and 11.3+/-5.0 fold increases, respectively). These data
      indicate that small quantities of endotoxin may move into the circulation from
      the large intestine after the sharp decrease in pH that occurs as a result of
      carbohydrate fermentation. Correlating these findings with in vitro studies
      suggests that LPS may primarily activate platelets, leading indirectly to the
      activation of leukocytes. Therefore, endotoxin may contribute in the initiation
      of the early inflammatory changes observed in experimental models of acute
      laminitis.

PMID- 19091427
TI  - A new method to discriminate immunogen-specific heavy-chain homodimer from
      heterotetramer immunoglobulin G directly in immunized dromedary whole plasma
      proteins: Western ligand blotting.
AB  - The variable domain of heavy-chain camelid antibodies (VHH), exclusively present
      in the homodimer IgGs (HC IgG), provides valuable ligands for diagnosis, imaging
      and therapy. These VHHs are efficiently produced from lymphocytes of immunized
      animals through phage display and recombination biotechnology. For VHH
      development it is desirable to identify animals with high affinity HC IgG
      response by monitoring antigen-binding in the course of immunization. The aim of
      this study was to propose a direct approach on whole plasma samples to
      distinguish between homodimer IgG and heterotetramer (IgG(1)) responses, and
      quantify them, using western ligand blotting (WLB). WLB consists here in
      electrophoretic separation of the target IgG subclasses on the basis of molecular
      size and binding of (125)I labeled antigen. First, we established the WLB
      parameters for titration of antigen-binding homodimers in relation to antigen
      binding total IgGs in ovalbumin-immunized dromedary plasma samples and
      demonstrated that the WLB is an alternative to ELISA for IgG subclass titration.
      As purification of IgG subclasses or availability of IgG subclass-specific
      antibodies is not necessary, WLB is more direct and practical for screening a
      large number of samples. Second, WLB was applied to study the pattern of
      homodimer and heterotetramer responses during the time-course of immunizations
      against three different types of immunogens. As these patterns can differ between
      animals and immunogens, the method may be useful for identifying animals
      displaying the desired antigen-specific homodimer IgG response. Lastly, WLB was
      also described in its variant form of dot ligand blotting for identifying antigen
      binding phages at the final step of a phage display experiment.

PMID- 19091428
TI  - Semicircular canal dehiscence in the pediatric population.
AB  - OBJECTIVES: (1) Identify the existence of semicircular canal bony dehiscence in
      the pediatric population; (2) determine the frequency of this finding in children
      over 3 years of age who have had temporal bone computed tomography (CT) imaging;
      (3) correlate the clinical history and audiological data to CT findings in this
      population. DESIGN AND SETTING: Retrospective review of temporal bone CT scans
      performed at a tertiary care children's hospital and retrospective chart review.
      PATIENTS: Children over 3 years of age who underwent a temporal bone CT scan
      between January 2006 and December 2006. RESULTS: Review of 131 temporal bone CT
      scans using multiplanar imaging techniques revealed evidence of semicircular
      canal bony dehiscence in 18 children older than 3 years of age. Dehiscence of the
      superior semicircular canal was identified in 14 patients while dehiscence of the
      posterior semicircular canal was identified in 5 patients. One patient had both
      the superior and posterior semicircular canal dehiscences. Retrospective chart
      review comparing children with and without semicircular canal dehiscence showed
      no significant difference in clinical history or audiological data. CONCLUSIONS:
      Semicircular canal dehiscence exists in the pediatric population. In this series,
      18 of 131 temporal bone CT scans were positive for bony dehiscence of the
      superior or posterior semicircular canals. Further study is required to determine
      the clinical significance of this radiographic finding.

PMID- 19091429
TI  - Middle ear disease in children with cleft palate: protocols for management.
AB  - OBJECTIVE: There is wide international variation in the protocols used for middle
      ear disease management in cleft palate patients. Ventilation tube (grommet)
      insertion may occur routinely at the time of palatoplasty or selectively on a
      separate occasion if symptomatic middle ear disease develops. The audiological
      and otologic outcomes of cleft palate patients were studied in a single
      institution over a timeframe in which both protocols were utilised. METHODS: This
      was a retrospective study of 234 cleft palate patients who underwent palatoplasty
      from 1990 to 2005 at Middlemore Hospital, Auckland, New Zealand. Data on hearing
      loss, middle ear disease, and tympanic membrane abnormalities was collected from
      clinical notes. Audiological data was obtained from pure tone audiogram reports.
      RESULTS: Forty-five patients had routine grommets inserted concurrent with
      palatoplasty and 189 patients were managed conservatively with selective grommet
      insertion if indicated. Grommets were subsequently required in 79 (41.8%) of
      these 189 patients. There was no difference in the incidence of persistent
      conductive hearing loss, but recurrent middle ear disease, tympanic membrane
      abnormalities, and the total number of grommet insertions were significantly
      higher in the routine grommet group. Poorer outcomes were noted in patients who
      had undergone a greater number of grommet insertions. CONCLUSION: No significant
      deterioration in audiological outcomes and better otologic outcomes were found in
      cleft palate patients undergoing selective grommet insertion compared to routine
      grommet insertion. It is recommended that ventilation tube placement occur in
      patients selected on the basis of symptomatic infection or significant hearing
      loss.

PMID- 19091430
TI  - A comparison between the Plateletworks-assay and light transmittance aggregometry
      for monitoring the inhibitory effects of clopidogrel.
AB  - A simple and rapid point-of-care platelet function assay that guides antiplatelet
      responses to aspirin and clopidogrel may be of great clinical value for the
      individual tailoring of therapy. The Plateletworks assay is based on single
      platelet counting and has been described as a promising point-of-care assay for
      the monitoring of the effects of the GP IIb/IIIa antagonists. However, data about
      its utility and reliability in monitoring the effects of thienopyridines is
      limited. In the present study we assessed reproducibility of the Plateletworks
      assay over time. In addition, a comparison between the Plateletworks assay and
      optical aggregometry was performed in a large cohort of patients on maintenance
      therapy with aspirin and clopidogrel. The Plateletworks assay demonstrated a good
      agreement with optical aggregometry in measuring the response to clopidogrel. The
      results of Plateletworks are, however, highly time dependent which implicates
      that measurements should be performed within 10 min.

PMID- 19091431
TI  - Scientific publications in cardiology and cardiovasology journals from Chinese
      authors in various parts of North Asia: 10-year survey of literature.
AB  - BACKGROUND: People of Chinese ethnicity make up one of the largest populations in
      the world. Heart and vessel diseases remain the leading cause of morbidity and
      mortality in China. The research status in cardiology and cardiovasology among
      Chinese individuals in the three major regions of China--Mainland (ML), Hong Kong
      (HK) and Taiwan (TW)--are unknown. The outputs of cardiology and cardiovasology
      articles published in international journals from the three regions were compared
      in this study. METHODS: Articles published in 83 journals related to cardiology
      and cardiovasology originating from the ML, TW and HK from 1998-2007 were
      retrieved from the PubMed database. The number of total articles, clinical trial,
      randomized controlled trial, case reports, impact factors (IF), citations, and
      articles published in top general medicine journals were conducted for quantity
      and quality comparisons. RESULTS: The total number of articles from the three
      regions increased significantly from 1998 to 2007 (from 154 to 591). There were
      2801 articles from ML (883), TW (1404) and HK (514) in the past ten years. The
      number of articles published per year from the ML (297) have exceeded those from
      TW (235) and HK (59) in 2007. The accumulated impact factor of the articles from
      TW (4082.736) was much higher than ML (2221.699) and HK (1673.049). HK had the
      highest average IF of cardiology and cardiovasology articles and the most
      articles published in top general medicine journals among the three regions.
      CONCLUSION: The total number of articles from the three major regions of China
      increased significantly from 1998 to 2007. The number of articles published per
      year from the ML have exceeded those from TW and HK. However, the quality of
      articles from TW and HK is better than that from ML.

PMID- 19091432
TI  - Tobacco taxes and regressivity.
AB  - Recent literature on tobacco taxation suggests that optimal tax rates should be
      very high. But such high taxes raise concerns over regressivity. Most econometric
      estimates of elasticities by income group use historic price data that are low,
      and the usefulness of such estimates is therefore questionable on account of the
      serious 'out of sample' prediction problem. To address that problem, this paper
      estimates price elasticities for different socioeconomic groups using recent
      Canadian survey data for a period during which prices rose to a level of about $7
      per pack. The results provide little reason to overturn the traditional concerns
      about regressivity.

PMID- 19091433
TI  - Financial incentives and physicians' prescription decisions on the choice between
      brand-name and generic drugs: evidence from Taiwan.
AB  - This paper tests the hypothesis of whether or not financial incentives affect a
      physician's prescription decision on the choice of generic versus brand-name
      drugs within a system in which physicians prescribe and dispense drugs. By using
      data obtained from Taiwan and focusing on diabetic patients, our empirical
      results provide several consistent findings in support of the hypothesis that
      profit incentives do affect the physician's prescribing decision, suggesting that
      physicians act as imperfect agents. An important implication of our findings is
      that rent seeking for profit margin between the reimbursement and the acquisition
      price instead of reducing costs is the major driving force behind generic
      substitution. As a result, the providers instead of the payers or consumers reap
      the financial benefits of generic substitution.

PMID- 19091434
TI  - The Disability Discrimination Act in the UK: helping or hindering employment
      among the disabled?
AB  - The enactment of the Americans with Disabilities Act (ADA) in 1990 triggered a
      substantial academic debate about its consequences on employment rates of
      disabled people. In contrast, the employment provision of the 1996 Disability
      Discrimination Act (DDA) in Britain has received little attention. Exploiting
      both pooled and longitudinal data, this paper provides robust evidence that,
      similar to the ADA in the USA, the DDA has had no impact on the employment rate
      of disabled people or possibly worsened it. Possible reasons for this are higher
      uncertainty around litigation costs, low levels of general awareness about the
      Act among disabled people and employers, and a lack of financial support.

PMID- 19091435
TI  - Inactivation of Enterobacter sakazakii in reconstituted infant formula by trans
      cinnamaldehyde.
AB  - Enterobacter sakazakii is an emerging pathogen which causes a life-threatening
      form of meningitis, necrotizing colitis and meningoencephalitis in neonates and
      children. Epidemiological studies implicate dried infant formula as the principal
      source of the pathogen. Trans-cinnamaldehyde is a major component of bark extract
      of cinnamon. It is classified as generally recognized as safe (GRAS) by the U.S.
      Food and Drug Administration, and is approved for use in food (21 CFR 182.60).
      The objective of this study was to determine the antibacterial effect of trans
      cinnamaldehyde on E. sakazakii in reconstituted infant formula. A 5-strain
      mixture of E. sakazakii was inoculated into 10 ml samples of reconstituted infant
      formula (at 6.0 log CFU/ml) containing 0%, 0.15%, 0.3% or 0.5% trans
      cinnamaldehyde. The samples were incubated at 37, 23, 8 or 4 degrees C for 0, 6,
      10 and 24 h, and the surviving populations of E. sakazakii at each sampling time
      were enumerated. In addition, potential cytotoxicity of trans-cinnamaldehyde, if
      any, was determined on human embryonic intestinal cells (INT-407). The treatments
      containing trans-cinnamaldehyde significantly reduced (P<0.05) the population of
      E. sakazakii, compared to the controls. Trans-cinnamaldehyde (0.5%) reduced the
      pathogen to undetectable levels by 4 h of incubation at 37 or 23 degrees C and 10
      h of incubation at 8 or 4 degrees C, respectively. Trans-cinnamaldehyde produced
      no cytotoxic effects on human embryonic intestinal cells at the tested
      concentrations. Results indicate that trans-cinnamaldehyde could potentially be
      used to kill E. sakazakii in reconstituted infant formula, however sensory
      studies are warranted before recommending its use.

PMID- 19091436
TI  - NMR-determined lipoprotein subclass profile predicts type 2 diabetes.
AB  - AIMS: To determine whether nuclear magnetic resonance (NMR)-determined
      lipoprotein profiles predict type 2 diabetes. METHODS: Subjects were 813 male and
      female participants in the Melbourne Collaborative Cohort Study, aged 40-69 years
      at baseline (1990-1994), and with a baseline fasting plasma glucose <7.0 mmol/L.
      Incident type 2 diabetes was identified in 1994-1998 by self-report and
      confirmation from doctors. Eligible cases and a random group of controls were
      selected, with NMR data available for 59 cases and 754 non-cases. RESULTS:
      Concentration of very low density lipoprotein (VLDL) particles (positive) and
      high density lipoprotein (HDL) particle size (negative) were selected by stepwise
      regression as predictors of type 2 diabetes. These associations were independent
      of other non-lipid risk factors, but not plasma triglycerides. Factor analysis
      identified a factor from NMR variables, explaining 47% of their variation, and
      characterized by a positive correlation with VLDL, particularly large and medium
      sized; more low density lipoprotein (LDL) that were smaller; and relatively
      smaller, but not more HDL particles. This factor was positively associated with
      diabetes incidence, but not independently of triglycerides. CONCLUSIONS: We
      identified an atherogenic NMR lipoprotein profile in people who developed
      diabetes, but this did not improve diabetes prediction beyond conventional
      triglyceride levels.

PMID- 19091437
TI  - Prevalence of macro- and microvascular complications among patients with type 2
      diabetes in Iran: a systematic review.
AB  - Although diabetes mellitus is becoming prevalent in Iran, no comprehensive data
      on diabetes-related complications exist. A systematic search of English and Farsi
      databases identified 26 publications on the prevalence of macro- and
      microvascular complications in adult Iranians with type 2 diabetes. Micro- and
      macroalbuminuria, retinopathy and neuropathy were highly prevalent and
      cardiovascular complications were prevalent. Valid studies on diabetic foot
      ulcers and lower limb amputations were few. Insufficient evidence of late
      complications precluded data extrapolation to the whole Iranian diabetic
      population. However, considering diabetes's high prevalence and impact on
      healthcare systems, current diabetes management in Iran requires further study.

PMID- 19091438
TI  - Long-term projections for diabetes-related work loss and limitations among U.S.
      adults.
AB  - We used data from the U.S. National Health Interview Survey to estimate the
      effect of diabetes on labor market outcomes. In the year 2050 an estimated 1.46
      million U.S. adults will not be working; 597,000 will be work disabled; and
      780,000 will have work limitations as a result of diabetes.

PMID- 19091439
TI  - Ribavirin: current role in the optimal clinical management of chronic hepatitis
      C.
AB  - Ribavirin in combination with peginterferon alfa shows strong clinical efficacy
      against chronic hepatitis C, and is now established as the standard of care.
      However, the precise role of ribavirin is still being defined, suggesting that
      optimal ribavirin dose should be maintained over the whole treatment period.
      Ribavirin dosage varies by bodyweight for genotype 1 disease (1000mg/day in
      patients <or =75kg and 1200mg/day in patients >75kg), whereas 800mg/day is
      sufficient to ensure optimal response in all genotype 2/3 patients. Similarly,
      genotype 1 patients benefit from 48 weeks of therapy, while 24 weeks is
      sufficient for genotype 2/3 disease. Recent data suggest treatment success is
      dependent on cumulative ribavirin exposure, as patients who receive <60% of the
      planned dose have lower response rates, regardless of whether reductions are from
      temporary interruptions or premature cessation of therapy. All patients should be
      monitored for hemolytic anemia, as early diagnosis allows management through
      small dose reductions and stepwise return to the target dose, maximizing
      cumulative exposure. Despite these recent advances in our knowledge, many
      questions remain, such as whether the role of ribavirin will change or even be
      eliminated as new therapies are developed.

PMID- 19091440
TI  - Acute hepatitis B in a healthcare worker: a case report of genuine vaccination
      failure.
AB  - BACKGROUND: Individuals who reach the antibody threshold level of 10IU/l against
      the surface protein of the hepatitis B virus (HBV) after completion of a series
      of hepatitis B vaccination are considered to be long-term protected against a
      clinically manifest HBV infection. CASE REPORT: Here we describe an acute
      hepatitis B infection in a patient who received five hepatitis B vaccinations.
      Although his initial response to vaccination was moderate, he finally reached an
      excellent hepatitis B surface antibody level (anti-HBs) titres of more than 1000
      IU/l in response to a booster vaccination with a recombinant DNA vaccine.
      Nevertheless, he developed full-blown acute hepatitis due to an HBV infection
      14years after this booster vaccination. A DNA analysis of the surface protein
      encoding region followed by phylogenetic analysis showed that our patient was
      infected with a normal HBV strain that is circulating among men who have sex with
      men. To our knowledge, this is the first report of a genuine hepatitis B
      vaccination failure in someone who acquired a high anti-HBs level in response to
      a recombinant DNA hepatitis B vaccine. CONCLUSION: Healthcare workers whose
      response to the initial hepatitis B vaccination is moderate might be vulnerable
      to hepatitis B virus infection.

PMID- 19091441
TI  - Treatment of brain metastasis from non-small cell lung cancer with whole brain
      radiotherapy and Gefitinib in a Chinese population.
AB  - BACKGROUND: Brain metastases (BM) represent one of the most common challenges
      related to non-small cell lung cancer (NSCLC), with evolving treatment
      strategies. We have conducted a phase II clinical trial in a Chinese population
      to evaluate concomitant treatment with whole brain radiotherapy (WBRT) and
      Gefitinib in patients with BM from NSCLC. The purpose of this study is to report
      the efficacy and toxicity of this treatment, and assess its impact on patient
      Quality of Life (QoL) and survival post-treatment. PATIENTS AND METHODS: Between
      October 2005 and January 2007, 21 patients were enrolled and received 40Gy/20f/4w
      WBRT. Gefitinib was administrated orally at a dosage of 250mg/day during the
      radiation course and was continued for each 28-day treatment cycle until
      progression of the disease, unacceptable toxicity, or withdrawal of consent. The
      primary end point of the study was tumor response and QoL. The secondary end
      points were toxicity and survival. Objective response rate according to the
      RECIST criteria was recorded. Health-related QoL was measured using FACT-Br
      (V4.0) and toxicity was evaluated and recorded using the NCI Common Toxicity
      Criteria. The Kaplan-Meier method was used to evaluate patient survival.
      Univariate analysis of patient characteristics and tumor responses was conducted
      using the Chi-square and Fisher's exact test. RESULTS: Four (19%) and 13 patients
      (62%) had a complete and partial response respectively, while 3 patients disease
      remained stable and 1 patient had progression of the disease. The overall
      response rate (81%, 95% confidence interval (CI): 58-95%) exceeded the goal per
      study design. The median progression-free survival and overall survival were 10.0
      months (95% CI: 7.5-12.5 months) and 13.0 months (95% CI: 8.2-17.8 months),
      respectively. The most frequent toxicities included rash (86%) and diarrhea
      (43%), with only 3 patients developing a grade III diarrhea. Other grade II or
      higher toxicities occurring in about 50% of patients included nausea, vomiting,
      headache, and fatigue. Most side effects were grade II and well tolerated by
      supportive care. Gender and cigarettes/year were predictive factors for the
      responses found in univariate analysis. All domains of QoL were significantly
      improved following treatment. CONCLUSION: Our data suggests that concomitant
      treatment was well tolerated, with promising activity and a significant
      improvement of QoL in a Chinese population with brain metastases from NSCLC.
      Although the data presented herewithin appears promising, more data from
      randomized trials are needed to further validate this regimen of WBRT/Gefitinib.

PMID- 19091442
TI  - Telomere length, telomeric proteins and DNA damage repair proteins are
      differentially expressed between primary lung tumors and their adrenal
      metastases.
AB  - INTRODUCTION: The development of molecular targeted therapies as anti-cancer
      strategies raises important questions regarding the biological and molecular
      behavior of the metastatic sites as compared to their corresponding primary
      tumors. We analysed telomere related markers (telomere length and telomeric
      proteins) and DNA damage repair (DDR) markers in a cohort of patients with
      surgically resected primary lung NSCLC and adrenal metastasis. These markers were
      selected for two reasons: (i) small molecule inhibitors of 'druggable' DDR
      components as well as telomere-interacting agents are already being developed for
      clinical use; and (ii) limited data is available comparing the expression of
      these biomarkers between primary tumors and their metastases. MATERIAL AND
      METHODS: We studied a single series of 21 patients who had undergone surgery of
      both their primary lung tumor and its related adrenal gland metastasis in a
      single Institution. DDR and telomeric proteins were analysed by
      immunohistochemistry and telomere length was assessed by fluorescent in situ
      hybridization in 17 paired samples. RESULTS: DDR activation was observed in
      primary tumors and their corresponding metastasis. However, higher levels of p
      Chk2 were observed in metastasis than in primary tumors (p=0.0113). This was not
      observed for p-ATM and gamma-H2AX. Telomere length was independent from primary
      or metastatic status (p=0.29). There was no correlation between primary and
      metastatic sites, although approximately 65% of metastases had shorter telomeres
      than their corresponding primary tumors. In the same way, telomeric protein
      expression was independent from primary/metastatic localization. Cluster analysis
      of each specimen according to its protein's expression levels and telomere length
      showed that matched primary tumors/adrenal metastasis were mostly separated into
      different clusters. Overall, our findings suggest that the levels of biomarkers
      analysed differ substantially between primary lung tumors and corresponding
      metastases. CONCLUSION: There are clear molecular discrepancies at the telomeric
      and DDR level between primary tumors and their corresponding metastases. Our
      results may have important implications for the development of molecular targeted
      therapies aiming at DNA damage repair and telomeric components. Our findings
      suggest that primary tumors and their relevant metastases may respond differently
      to such approaches.

PMID- 19091443
TI  - Spitz nevi: In vivo confocal microscopic features, dermatoscopic aspects,
      histopathologic correlates, and diagnostic significance.
AB  - BACKGROUND: Spitz nevi are benign melanocytic tumors, sometimes misdiagnosed as
      malignant melanoma (MM). OBJECTIVE: We sought identification of characteristic in
      vivo microscopic features of Spitz nevi, their histopathologic correlates, and
      diagnostic usefulness. METHODS: Forty Spitz nevi were studied by in vivo confocal
      microscopy and dermatoscopy, evaluating histopathologic correlates, and compared
      with 40 MMs and 40 Clark nevi. RESULTS: Some histologic aspects characteristic
      for Spitz nevus diagnosis were correlated with confocal features, comprising some
      that can be useful for atypical Spitz nevus classification. The most striking
      features for differentiating Spitz nevi from MMs were the presence of sharp
      border cut-off, junctional nests, and melanophages. LIMITATIONS: No correlates
      were found for other aspects, such as Kamino bodies, hyperkeratosis, acanthosis,
      mitoses, and maturation with depth. The impossibility of exploring deeper aspects
      hampered an accurate distinction from MMs in some cases. CONCLUSION: Confocal and
      dermatoscopic examination enabled the identification of different Spitz
      categories with different histologic substrates.

PMID- 19091446
TI  - Seasonal and spatial variability of (210)Po, (238)U and (239+240)Pu levels in the
      river catchment area assessed by application of neural-network based
      classification.
AB  - The present study deals with the application of self-organizing maps (SOM) in
      order to model, classify and interpret seasonal and spatial variability of
      (210)Po, (238)U and (239+240)Pu levels in the Vistula river basin. The data set
      represents concentration values for 3 alpha emitters ((210)Po, (238)U and
      (239+240)Pu) measured in surface water samples collected at 19 different sampling
      locations (8 in major Vistula stream while 11 in right or left Vistula
      tributaries) during four seasons (winter, spring, summer and autumn) in the
      framework of a one-year quality monitoring study. The advantages of an SOM
      algorithm, its classification and visualization ability for environmental data
      sets, are stressed. The neural-network based classification made it possible to
      reveal specific patterns related to both seasonal and spatial variability. In the
      middle and upper part of Vistula catchment as well as in the right-shore
      tributaries, concentrations of (210)Po and (238)U during summer and winter are
      the lowest. Concentrations of (210)Po and (238)U increase significantly during
      spring and autumn in the Vistula river catchment, especially in the delta of
      Vistula river. High concentration of anthropogenic originated (239+240)Pu
      indicates "site-specific" character of pollution in two large left-shore
      tributaries located in the middle part of the Vistula drainage area. Efficient
      classification of sampling locations could lead to an optimization of river
      radiochemical sampling networks and to a better tracing of natural and
      anthropogenic changes along Vistula river stream.

PMID- 19091445
TI  - Coronary heart disease is associated with non-amnestic mild cognitive impairment.
AB  - The progression of amnestic mild cognitive impairment (a-MCI) to Alzheimer's
      disease and hypothesized progression of non-amnestic mild cognitive impairment
      (na-MCI) to non-degenerative or vascular dementias suggest etiologic differences.
      We examined the association between coronary heart disease (CHD) and mild
      cognitive impairment (MCI) subtypes in a population-based cohort. Participants
      (n=1969; aged 70-89 years) were evaluated using the Clinical Dementia Rating
      Scale, a neurological examination, and neuropsychological testing for diagnoses
      of normal cognition, MCI, or dementia. CHD was defined as a history of myocardial
      infarction, angina, angiographic coronary stenosis, or coronary revascularization
      and ascertained by participant interview and from medical records. CHD was
      significantly associated with na-MCI (OR=1.93; 95% CI=1.22-3.06) but not with a
      MCI (OR=0.94; 95% CI=0.69-1.28). In contrast, ApoE E4 allele was significantly
      associated with a-MCI (OR=1.75; 95% CI=1.28-2.41), but not with na-MCI (OR=1.17;
      95% CI=0.69-2.00). The association of CHD with prevalent na-MCI but not with a
      MCI suggests that CHD and na-MCI may have similar underlying etiologies.

PMID- 19091447
TI  - Proceedings of the International Symposium on In-situ Nuclear Metrology as a tool
      for Radioecology. September 6-8, 2006. Kusadasi, Turkey.

PMID- 19091444
TI  - Cognition in healthy aging is related to regional white matter integrity, but not
      cortical thickness.
AB  - It is well established that healthy aging is accompanied by structural changes in
      many brain regions and functional decline in a number of cognitive domains. The
      goal of this study was to determine (1) whether the regional distribution of age
      related brain changes is similar in gray matter (GM) and white matter (WM)
      regions, or whether these two tissue types are affected differently by aging, and
      (2) whether measures of cognitive performance are more closely linked to
      alterations in the cerebral cortex or in the underlying WM in older adults (OA).
      To address these questions, we collected high-resolution magnetic resonance
      imaging (MRI) data from a large sample of healthy young adults (YA; aged 18-28)
      and OA (aged 61-86 years). In addition, the OA completed a series of tasks
      selected to assess cognition in three domains: cognitive control, episodic
      memory, and semantic memory. Using advanced techniques for measuring cortical
      thickness and WM integrity, we found that healthy aging was accompanied by
      deterioration of both GM and WM, but with distinct patterns of change: Cortical
      thinning occurred primarily in primary sensory and motor cortices, whereas WM
      changes were localized to regions underlying association cortices. Further, in
      OA, we found a striking pattern of region-specific correlations between measures
      of cognitive performance and WM integrity, but not cortical thickness.
      Specifically, cognitive control correlated with integrity of frontal lobe WM,
      whereas episodic memory was related to integrity of temporal and parietal lobe
      WM. Thus, age-related impairments in specific cognitive capacities may arise from
      degenerative processes that affect the underlying connections of their respective
      neural networks.

PMID- 19091448
TI  - Effect of trunk inclination on lower limb joint and lumbar moments in able men
      during the stance phase of gait.
AB  - BACKGROUND: Though the effect of imposed trunk posture affects walking patterns
      little is known about the effect of natural orientation of the trunk on gait. The
      objectives of this study are to test if the lower limb joint and thoraco-lumbar
      moments are similar in subjects who maintain an average natural forward or
      backward trunk inclination during gait and verify if the lower limbs are equally
      affected. METHODS: Twenty-five young men were divided according to their natural
      backward or forward trunk inclination during level walking. Ankle, knee, hip and
      thoraco-lumbar moments were calculated by an inverse dynamic approach for the two
      limbs. A two-way ANOVA was performed on peak lower limb moments. A one-way ANOVA
      was performed on thoraco-lumbar peak moments. FINDINGS: There was a main effect
      for both trunk inclinations and lower limb sides but no interaction. For the
      forward leaners, the duration of hip extension moment was longer (P<0.001) while
      the hip flexion moment was 1.3 times smaller (P<0.001). Differences between the
      lower limb sides were noted in all joints but at push-off of the stance phase
      only. The two thoraco-lumbar extension moments were, respectively, 1.4 times
      higher for the forward leaners while the two flexion moments were approximately
      1.4 times higher for the backward leaners. INTERPRETATIONS: The backward leaners
      propel themselves with a strong hip flexor activity at push-off while the forward
      leaners use their hip muscles throughout stance. These results support the idea
      that trunk inclinations and moment variations are associated with the type of
      walking patterns.

PMID- 19091449
TI  - Knee-extension strength, postural control and function are related to fracture
      type and thigh edema in patients with hip fracture.
AB  - BACKGROUND: Post-surgery thigh edema, loss of knee-extension strength, and
      reduced physical performance are common following a hip fracture. It is not known
      if knee-extension strength and physical performance are related to the edema and
      fracture type. The aim of this study was to examine the influence of fracture
      type and post-surgery edema on physical performances in patients with hip
      fracture. METHODS: Fifteen women and five men admitted from their own home to an
      acute orthopedic hip fracture unit were examined. Ten had cervical and ten had
      intertrochanteric fractures. Correlations between fracture type and thigh edema
      in the fractured limb (% non-fractured) to physical performances of basic
      mobility, postural control (sway), and isometric knee-extension strength were
      examined. All measures, except those of basic mobility, were conducted at the
      time of discharge, 8.5 days post-surgery. FINDINGS: Patients with
      intertrochanteric fractures had greater edema (111% non-fractured limb) compared
      with cervical fractures (104% non-fractured, P<0.001). Thigh edema was
      significantly correlated to lower scores of basic mobility (r=-0.61, P=0.004),
      reduced postural control (r=0.67, P=0.001), and fractured limb knee-extension
      strength deficit ([% non-fractured], r=-0.77, P<0.001), explaining between 32%
      and 59% of the variance (r(2)) in performances. INTERPRETATION: Our results
      indicate that fracture type and the corresponding thigh edema are important
      factors influencing physical performances after hip fracture. These findings have
      important implications for rehabilitation programs and for further research in
      patients with hip fracture.

PMID- 19091450
TI  - Intergenerational class mobility and cardiovascular mortality among Swedish
      women: a population-based register study.
AB  - Class inequalities in cardiovascular disease (CVD) mortality are well documented,
      but the impact of intergenerational class mobility on CVD mortality among women
      has not been studied thoroughly. We examined whether women's mobility
      trajectories might contribute to CVD mortality beyond what could be expected from
      their childhood and adult social class position. The Swedish Work and Mortality
      Data Base provided childhood (1960) and adulthood (1990) social indicators. Women
      born 1945-59 (N=791 846) were followed up for CVD mortality 1990-2002 (2019
      deaths) by means of logistic regression analysis. CVD mortality risks were
      estimated for 16 mobility trajectories. Gross and net impact of four childhood
      and four adult classes, based on occupation, were analysed for mortality in
      ischemic heart disease (IHD), stroke, other CVD, - and all CVD. Differences
      between the two most extreme trajectories were 10-fold, but the common trajectory
      of moving from manual to non-manual position was linked to only a slight excess
      mortality (OR=1.26) compared to the equally common trajectory of maintaining a
      stable non-manual position (reference category). Moving into adult manual class
      resulted in an elevated CVD mortality whatever the childhood position (ORs varied
      between 1.42 and 2.24). After adjustment for adult class, childhood class had
      some effect, in particular there was a low risk of coming from a self-employed
      childhood class on all outcomes (all ORs around=0.80). A woman's own education
      had a stronger influence on the mortality estimates than did household income.
      Social mobility trajectories among Swedish women are linked to their CVD
      mortality risk. Educational achievement seems to be a key factor for
      intergenerational continuity and discontinuity in class-related risk of CVD
      mortality among Swedish women. However, on mutual adjustment, adult class was
      much more closely related to CVD mortality than was class in childhood.

PMID- 19091451
TI  - Neither rain nor hail nor sleet nor snow: provider perspectives on the challenges
      of weather for home and community care.
AB  - This paper contributes to the literature on the geographies of care and
      caregiving by examining the implications of weather for providing home and
      community care for children and older adults. Integrating research from two
      previous qualitative studies of formal and informal care provisioning in Ontario,
      Canada, the authors re-analyzed semi-structured interviews with 83 directors,
      managers, paid staff, volunteers and family members to examine the challenges
      they faced when providing care during the winter season. Similar to other
      settings where winter conditions like snow, ice and cold temperatures are
      commonplace, the studies were set within a health policy context in which there
      is not enough recognition of the difficulties of weather for coordinating,
      managing and providing care to disabled, injured, chronically ill and frail
      individuals. The re-analysis focused on how winter conditions translate into
      geographical, administrative, economic, operational, physical, social and
      psychological barriers within and across different 'scales of care'. The findings
      indicate that the problems posed by weather are crucial yet often underestimated
      aspects of home and community care provided by formal and informal caregivers.
      The analysis of weather-related challenges for care provisioning needs to be
      extended to other seasonal conditions (e.g., the challenges of delivering care in
      extreme heat), to the developing world and even to the burgeoning debates on the
      health implications of global environmental change.

PMID- 19091452
TI  - Long-term survival of endodontically treated, maxillary anterior teeth restored
      with either tapered or parallel-sided glass-fiber posts and full-ceramic crown
      coverage.
AB  - OBJECTIVES: This retrospective study investigated the clinical effectiveness over
      up to 8 years of parallel-sided and of tapered glass-fiber posts, in combination
      with either hybrid composite or dual-cure composite resin core material, in
      endodontically treated, maxillary anterior teeth covered with full-ceramic
      crowns. METHODS: The study population comprised 192 patients and 526
      endodontically treated teeth, with various degrees of hard-tissue loss, restored
      by the post-and-core technique. Four groups were defined based on post shape and
      core build-up materials, and within each group post-and-core restorations were
      assigned randomly with respect to root morphology. Inclusion criteria were
      symptom-free endodontic therapy, root-canal treatment with a minimum apical seal
      of 4mm, application of rubber dam, need for post-and-core complex because of
      coronal tooth loss, and tooth with at least one residual coronal wall. Survival
      rate of the post-and-core restorations was determined using Kaplan-Meier
      statistical analysis. RESULTS: The restorations were examined clinically and
      radiologically; mean observation period was 5.3 years. The overall survival rate
      of glass-fiber post-and-core restorations was 98.5%. The survival rate for
      parallel-sided posts was 98.6% and for tapered posts was 96.8%. Survival rates
      for core build-up materials were 100% for dual-cure composite and 96.8% for
      hybrid light-cure composite. CONCLUSIONS: For both glass-fiber post designs and
      for both core build-up materials, clinical performance was satisfactory. Survival
      was higher for teeth retaining four and three coronal walls.

PMID- 19091453
TI  - Timing of defibrillation shocks for resuscitation of rapid ventricular
      tachycardia: does it make a difference?
AB  - Under current resuscitation guidelines symptomatic ventricular tachycardia (VT)
      with a palpable pulse is treated with synchronised cardioversion to avoid
      inducing ventricular fibrillation (VF), whilst pulseless VT is treated as VF with
      rapid administration of full defibrillation energy unsynchronised shocks. The
      additional delay in setting up the ECG to provide accurate synchronisation has
      been the main reason for advocating this approach, although many current
      defibrillators allow accurate synchronisation via just the adhesive defibrillator
      pads. The aim of this study was to investigate whether the timing of
      defibrillatory shocks in rapid VT-affected resuscitation outcome. The timings of
      the shocks relative to the QRS complex were used to define whether each shock was
      acting as a 'synchronised' or 'unsynchronised' shock. The study was a
      retrospective review of all diagnostic electrophysiological studies performed at
      Papworth Hospital. A total of 271 studies for ventricular arrhythmias were
      identified, with 144 studies resulting in stable monomorphic VT being induced. Of
      these VT episodes, 40 stopped spontaneously, 61 cases were terminated with anti
      tachycardia pacing, 1 required cardioversion for slow but incessant VT and 42
      required defibrillation for severe haemodynamic compromise/cardiac arrest. The
      electronic recordings of the defibrillation episodes were analysed to investigate
      the effects of shock timing on outcome. Of the 42 patients who required
      defibrillation, 30 had shocks delivered within a 100 ms window of the peak of the
      QRS complex. Of these, 28 patients converted to a perfusing rhythm and 2 patients
      deteriorated from VT to VF as a result of the defibrillation shock. The remaining
      12 patients received shocks outside this window, with 5 converting to a perfusing
      rhythm and 7 deteriorating to VF. Defibrillator shocks within the QRS complex had
      a success rate of 93% compared to a success rate of 42% for outside the QRS
      complex (p=0.0016 two-tailed Fishers' exact test, odds ratio=19.6, 95% limits=3.1
      123.1). There was no significant effect of age or sex of the patient, the
      underlying heart disease, rate of VT or anti-arrhythmic medication on the
      outcome, although the number of patients was too small to definitively exclude
      this. Therefore, defibrillation shocks delivered shortly after the peak of the
      QRS complex in rapid VT do appear to offer significant advantages over
      defibrillation shocks at other parts of the cardiac cycle for very rapid
      ventricular tachycardia.

PMID- 19091454
TI  - Reducing laparoscopic radical prostatectomy false-positive margin rates using
      cyanoacrylate tissue glue.
AB  - BACKGROUND: Trauma to the prostate surface from laparoscopic instruments may have
      a role in creating false-positive margins during laparoscopic radical
      prostatectomy (LRP). OBJECTIVE: To determine the feasibility of using
      cyanoacrylate glue to repair iatrogenic lacerations and to evaluate the glue's
      effect on the positive surgical margin rates of LRP specimens. DESIGN, SETTING,
      AND PARTICIPANTS: We used porcine kidneys as a surrogate experimental tissue to
      help determine the quality, robustness, and adequacy of glued repairs in
      experimentally created lacerations. A matched control group of unrepaired kidney
      specimens and kidney specimens repaired with glue were subjected to full
      histopathologic processing. Exposure of a nephron to surface marker ink was
      considered to be a "positive margin." The efficacy and impact of glue repairs on
      LRP specimens that had sustained iatrogenic intraoperative surface trauma were
      also assessed. MEASUREMENTS: We evaluated the success of glue repair in
      preventing subcapsular renal parenchymal staining. We also compared the rate of
      positive margins in LRP specimens with and without routine glue repair of the
      surface of the prostate. RESULTS AND LIMITATIONS: The glue remained effective
      throughout the entire laboratory process and did not interfere with
      histopathologic assessment. As hypothesised, cyanoacrylate glue repair of the
      renal lacerations prevented staining of subcapsular tissues with marker dye and
      therefore prevented what might otherwise be considered false-positive staining.
      The rate of positive margins of the 40 LRP specimens without glue repair was 35%,
      compared with a rate of 10% for 40 glue-repaired specimens. The limitations of
      the study are that follow-up was short and that the prostatectomy specimens were
      compared with consecutive controls rather than with matched randomised controls.
      CONCLUSIONS: Cyanoacrylate glue is a novel, inexpensive, and very effective
      prostate repair agent that does not interfere with histologic processing. It is
      possible to accurately repair iatrogenic prostate lacerations with cyanoacrylate
      glue and, in doing so, to considerably reduce the rate of spurious false-positive
      surgical margins.

PMID- 19091455
TI  - Editorial comment on: Reducing laparoscopic radical prostatectomy false-positive
      margin rates using cyanoacrylate tissue glue.

PMID- 19091456
TI  - Editorial comment on: Reducing laparoscopic radical prostatectomy false-positive
      margin rates using cyanoacrylate tissue glue.

PMID- 19091457
TI  - Brain impalement by an angle metal bar.
AB  - The author reports the case of a 37-year-old right-handed man who was impaled in
      the head by an angle metal bar at a construction work site. Impalement injuries
      of the brain are rare, and their management is complex. The surgical treatment of
      the injury and the medical management of complications are described in detail.
      The patient made a good recovery although he has functional deficits related to
      the injury to his frontal lobes.

PMID- 19091458
TI  - Liver cancer: descriptive epidemiology and risk factors other than HBV and HCV
      infection.
AB  - The incidence of liver cancer is high in all low-resource regions of the world,
      with the exception of Northern Africa and Western Asia. The estimated worldwide
      number of new cases of liver cancer in 2002 is 600,000, of which 82% are from
      developing countries. Given the poor survival from this disease, the estimated
      number of deaths is similar to that of new cases. Hepatocellular carcinoma (HCC)
      is the main form of liver cancer. A part from chronic infections with Hepatitis B
      and Hepatitis C viruses, which are the main causes of HCC, contamination of
      foodstuff with aflatoxins, a group of mycotoxins produced by the fungi
      Aspergillus flavus and Aspergillus parasiticus, is an important contributor to
      HCC burden in many low-income country. Alcoholic cirrhosis is an important risk
      factor for HCC in populations with low prevalence of HBV and HCV infection, and
      the association between tobacco smoking and HCC is now established. Diabetes is
      also related to an excess risk of HCC and the increased prevalence of overweight
      and obesity likely contributes to it. The second most important type of liver
      cancer is cholangiocarcinoma, whose main known cause is infestation with the
      liver flukes, Opistorchis viverrini and Clonorchis sinensis, which is frequent in
      some areas in South-East Asia. Angiosarcoma is a rare form of liver cancer whose
      occurence is linked to occupational exposure to vinyl chloride.

PMID- 19091459
TI  - p53 hot-spot mutants increase tumor vascularization via ROS-mediated activation
      of the HIF1/VEGF-A pathway.
AB  - The function of p53 tumor suppressor is often altered in various human tumors
      predominantly through missense-mutations resulting in accumulation of mutant
      proteins. We revealed that expression of p53 proteins with amino-acid
      substitutions at codons 175 (R175H), 248 (R248W), and 273 (R273H), representing
      the hot-spots of mutations in various human tumors, increased the number of
      vessels in HCT116 human colon carcinoma xenografts and, as a result, accelerated
      their growth. Stimulation of tumor angiogenesis was connected with about 2-fold
      increase in intracellular level of reactive oxygen species (ROS). Antioxidant N
      acetyl-l-aspartate (NAC) decreased vessels number in tumors formed by cells with
      inactivated p53 and inhibited their growth. Effect of ROS on angiogenesis in
      tumors expressing hot-spot p53 mutants was correlated with their ability to
      increase a content of HIF1 transcriptional factor responsible for up-regulation
      of VEGF-A mRNAs.

PMID- 19091460
TI  - Hexachlorophene suppresses beta-catenin expression by up-regulation of Siah-1 in
      EBV-infected B lymphoma cells.
AB  - Many studies have shown that the activation of beta-catenin signaling can promote
      oncogenesis, and it is therefore of interest to find agents that modulate this
      pathway. Recent work has shown using B lymphoma cells that infection by Epstein
      Barr virus (EBV) and expression of its latent membrane protein (LMP)-1, cause
      increases in the expression of beta-catenin and cellular transformation.
      Conversely, results from cell-based small molecule screening studies have shown
      that the antibiotic hexachlorophene can down-regulate beta-catenin in colon
      cancer cells. Here we report that hexachlorophene also counteracts the elevated
      beta-catenin levels in EBV-infected B lymphomas. This is associated with
      restoration in levels of Siah-1 (an E3 ubiquitin ligase that is active in beta
      catenin regulation) which had been diminished by LMP-1. Our results suggest that
      Siah-1 is targeted by both LMP-1 and hexachlorophene with opposite effects. The
      hexachlorophene modulation of Siah-1 and beta-catenin is independent of p53 and
      results in reduced expression of cyclin-D1 and c-Myc (target genes of beta
      catenin), leading to the growth arrest of B lymphoma cells. From these results we
      propose that hexachlorophene may provide a novel therapeutic strategy for EBV
      infected B lymphoma cells by reducing beta-catenin levels via the restoration of
      Siah-1.

PMID- 19091461
TI  - Combined effects of terazosin and genistein on a metastatic, hormone-independent
      human prostate cancer cell line.
AB  - Metastatic prostate cancer progresses from androgen-dependent to androgen
      independent. Terazosin, a long-acting selective alpha1-adrenoreceptor antagonist,
      induces apoptosis of prostate cancer cells in an alpha1-adrenoreceptor
      independent manner, while genistein, a major soy isoflavone, inhibits the growth
      of several types of cancer cells. The present study was designed to test the
      therapeutic potential of a combination of terazosin and genistein using a
      metastatic, hormone-independent prostatic cancer cell line, DU-145. Terazosin or
      genistein treatment inhibited the growth of DU-145 cells in a dose-dependent
      manner, whereas had no effect on normal prostate epithelial cells. Addition of 1
      microg/ml of terazosin, which was inactive alone, augmented the growth inhibitory
      effect of 5 microg/ml of genistein. Co-treatment with terazosin resulted in the
      genistein-induced arrest of DU-145 cells in G2/M phase being overridden and an
      increase in apoptotic cells, as evidenced by procaspase-3 activation and PARP
      cleavage. The combination also caused a greater decrease in the levels of the
      apoptosis-regulating protein, Bcl-XL, and of VEGF165 and VEGF121 than genistein
      alone. In conclusion, the terazosin/genistein combination was more effective in
      inhibiting cell growth and VEGF expression as well as inducing apoptosis of the
      metastatic, androgen-independent prostate cancer cell line, DU-145, than either
      alone. The doses used in this study are in lower and nontoxic anticancer dosage
      range, suggesting this combination has potential for therapeutic use.

PMID- 19091462
TI  - A common repertoire of autoantibodies is shared by cancer and autoimmune disease
      patients: Inflammation in their induction and impact on tumor growth.
AB  - The repertoire of autoantibodies found in cancer patients partly overlaps with
      that typical of patients with autoimmune diseases. Beside the biochemical and
      immunological properties of the target antigens and their altered expression in
      tumor tissues, the intratumoral inflammatory context can play a key role in the
      induction of autoimmune disease-associated autoantibodies in cancer patients.
      Furthermore, the impact of such antibodies on cancer growth and progression can
      be deeply influenced by the interplay with inflammation. The characterization of
      the spontaneous humoral responses occurring in cancer patients, of the mechanisms
      that trigger and sustain the autoantibody response and of the biological effects
      of such autoantibodies may help the rational design of anti-cancer
      immunotherapeutic protocols.

PMID- 19091463
TI  - Removal of phosphate from aqueous solution by red mud using a factorial design.
AB  - The purpose of the work is to study the adsorption of phosphate on red mud from
      aqueous solutions using 2(3) full factorial designs. The important parameters,
      which affect the removal efficiency of phosphate and final pH of solution
      (pH(f)), such as phosphate concentration, initial pH of solution (pH(i)) and the
      red mud dosage were investigated. The effects of individual variables and their
      interaction effects for dependent variables, namely, phosphate removal efficiency
      and pH(f) were determined. The results of the study showed that phosphate removal
      efficiency and pH(f) were found to be 97.6% and 10.9 with optimal reaction
      conditions initial phosphate concentration 25 mg l(-1), red mud dosage 1.5 g l(
      1), pH(i) 3.0, respectively. It was found that adequate amount of calcium ions
      and higher final pH than 9 are ideal conditions for maximum phosphate removal.

PMID- 19091464
TI  - Zincon-modified activated carbon for solid-phase extraction and preconcentration
      of trace lead and chromium from environmental samples.
AB  - A new method that utilizes zincon-modified activated carbon (AC-ZCN) as a solid
      phase extractant has been developed for simultaneous preconcentration of trace
      Cr(III) and Pb(II) prior to the measurement by inductively coupled plasma optical
      emission spectrometry (ICP-OES). The separation/preconcentration conditions of
      analytes were investigated, including effects of pH, the shaking time, the sample
      flow rate and volume, the elution condition and the interfering ions. At pH 4,
      the maximum adsorption capacity of Cr(III) and Pb(II) onto the AC-ZCN were 17.9
      and 26.7 mg g(-1), respectively. The adsorbed metal ions were quantitatively
      eluted by 1 mL of 0.1 mol L(-1) HCl. Common coexisting ions did not interfere
      with the separation. According to the definition of IUPAC, the detection limits
      (3 sigma) of this method for Cr(III) and Pb(II) were 0.91 and 0.65 ng mL(-1),
      respectively. The relative standard deviation under optimum condition is less
      than 3.5% (n=8). The method has been applied for the determination of Cr(III) and
      Pb(II) in biological materials and water samples with satisfactory results.

PMID- 19091465
TI  - Trace determination and chemical speciation of selenium in environmental water
      samples using catalytic kinetic spectrophotometric method.
AB  - A catalytic kinetic method is described for the determination of Se(IV), Se(VI)
      and total inorganic selenium in water based on the catalytic effect of Se(IV) on
      the reduction of bromate by hydrazine dihydrochloride in acidic media. The
      generated bromine decolorized methyl orange (MO) and the reaction was monitored
      spectrophotometrically at 507 nm as a function of time. The initial rate and
      fixed time methods were adopted for the determination and speciation of inorganic
      selenium. Under two optimum conditions, the calibration graphs are linear in the
      range 0-126.3 and 0-789.6 microg L(-1) of Se(IV) for the initial rate method and
      0-315.8 and 0-789.6 microg L(-1) of Se(IV) for the fixed time method. The
      detection limits were 1.3 and 14.7 microg L(-1) for the initial rate and fixed
      time methods, respectively. The proposed methods were validated statistically and
      through recovery studies in environmental water samples. The relative standard
      deviation in the determination of 31.6-94.8 microg L(-1) of Se(IV) and Se(VI) was
      less than 6%. Analyses of standard reference materials for selenium using initial
      rate and fixed time methods showed that the proposed methods have good accuracy.
      Se(IV), Se(VI) and total inorganic selenium in environmental water samples have
      been successfully determined by this method after selective reduction of Se(VI)
      to Se(IV).

PMID- 19091466
TI  - Removal of chromium Cr(VI) by low-cost chemically activated carbon materials from
      water.
AB  - Low-cost, chemically activated carbon materials, Pellet-600 and PVA-300, were
      prepared at relatively low temperatures and show more effective removal
      efficiency of Cr(VI) from water than commercially available activated carbons
      tested. The Pellet-600 is a pelletized carbon material with high mesoporous
      volumes and surface area, and the PVA-300 is composed of a high surface area
      carbon coating on a fiberglass mat substrate. A much faster adsorption kinetics
      and a much higher adsorption capacity for Cr(VI) are achieved by the Pellet-600.
      At very low concentrations of Cr(VI), the PVA-300 displays a strong adsorption
      ability for Cr(VI). XPS data show an increase in the atomic ratio of Cr/C and
      oxidation of carbon materials after adsorption of Cr(VI). These results suggest
      that a high content of mesopores with a high surface area and surface functional
      groups greatly improve the Cr(VI) removal efficiency from water.

PMID- 19091467
TI  - Comparison of the fixation effects of heavy metals by cement rotary kiln co
      processing and cement based solidification/stabilization.
AB  - Cement rotary kiln co-processing of hazardous wastes and cement based
      solidification/stabilization could both immobilize heavy metals. The different
      retention mechanisms of the two technologies lead to different fixation effects
      of heavy metals. The same amount of heavy metal compounds were treated by the two
      types of fixation technologies. Long-term leaching test (160 days), the maximum
      availability leaching test (NEN 7341) and a modified three-step sequential
      extraction procedure, proposed by the Commission of the European Communities
      Bureau of Reference (BCR) were employed to compare the fixation effects of the
      two fixation technologies. The leaching concentrations in NEN 7341 and long-term
      leaching tests were compared with identification standard for hazardous wastes
      (GB5085.3-1996) and drinking water standard (GB5749-2005). The results indicate
      that the leaching concentrations of the long-term leaching test and NEN 7341 test
      were lower than the regulatory limits and the leached ratios were small. Both
      cement based solidification/stabilization and cement rotary kiln co-processing
      could effectively fix heavy metals. Calcination in a cement rotary kiln and the
      following hydration that follows during cement application could fix As, Cd, Pb
      and Zn more effectively and decrease the release to the environment. Cement
      solidification/stabilization technology has better effect in immobilizing Cr and
      Ni. Cr wastes are more fitful to be treated by cement
      solidification/stabilization.

PMID- 19091468
TI  - Divergent peripheral effects of pituitary adenylate cyclase-activating
      polypeptide-38 on nociception in rats and mice.
AB  - Pituitary adenylate cyclase-activating polypeptide-38 (PACAP-38) and its
      receptors have been shown in the spinal dorsal horn, on capsaicin-sensitive
      sensory neurons and inflammatory cells. The role of PACAP in central pain
      transmission is controversial, and no data are available on its function in
      peripheral nociception. Therefore, the aim of the present study was to analyze
      the effects of locally or systemically administered PACAP-38 on nocifensive
      behaviors, inflammatory/neuropathic hyperalgesia and afferent firing.
      Intraplantar PACAP-38 (0.2nmol) injection inhibited carrageenan-evoked
      inflammatory mechanical allodynia, mild heat injury-induced thermal hyperalgesia,
      as well as nocifensive behaviors in the early and late phases of the formalin
      test in rats. However, the above dose did not alter basal mechanical or heat
      thresholds. In mice, PACAP-38 (0.2nmol/kg s.c.) significantly diminished acetic
      acid-induced abdominal contractions, but exerted no effect on sciatic nerve
      ligation-induced neuropathic mechanical hyperalgesia. In contrast, local PACAP-38
      injection markedly increased rotation-induced afferent firing in the inflamed rat
      knee joint clearly demonstrating a peripheral sensitization in this organ. These
      actions were blocked by VPAC1/VPAC2 receptor antagonist pretreatment, but were
      not altered by PAC1 receptor antagonism. This paper presents the first data for
      the peripheral actions of PACAP-38 on nociceptive transmission mediated by VPAC
      receptors. These effects seem to be divergent depending on the mechanisms of
      nociceptor activation and the targets of PACAP actions. In acute somatic and
      visceral inflammatory pain models, PACAP exerts anti-nociceptive, anti
      hyperalgesic and anti-allodynic effects. It has no significant peripheral role in
      traumatic mononeuropathy, but induces mechanical sensitization of knee joint
      primary afferents.

PMID- 19091469
TI  - Genuine antihyperalgesia by systemic diazepam revealed by experiments in GABAA
      receptor point-mutated mice.
AB  - Ionotropic gamma-aminobutyric acid (GABA(A)) receptors control the relay of
      nociceptive signals at several levels of the neuraxis. Experiments with
      systemically applied benzodiazepines, which enhance the action of GABA at these
      receptors, have suggested both anti- and pronociceptive effects. The
      interpretation of such experiments has been notoriously difficult because of
      confounding sedation. Here, we have used genetically engineered mice, which carry
      specific benzodiazepine-insensitive GABA(A) receptor subunits, to test whether
      diazepam, a frequently used classical benzodiazepine, exerts antihyperalgesia
      after systemic administration in the formalin test, a model of tonic nociception.
      In wild-type mice, systemic diazepam (3-30 mg/kg, p.o.) dose-dependently reduced
      the number of formalin-induced flinches during both phases of the test by about
      40-70%. This antinociception was reversed by the benzodiazepine site antagonist
      flumazenil (10mg/kg, i.p.), but fully retained in GABA(A) receptor alpha1 point
      mutated mice, which were resistant against the sedative action of diazepam.
      Experiments carried out in mice with two diazepam-insensitive subunits
      (alpha1/alpha2, alpha1/alpha3 and alpha1/alpha5 double point-mutated mice)
      allowed addressing the contribution of alpha2, alpha3 and alpha5 subunits to
      systemic diazepam-induced antihyperalgesia in the absence of sedation. The
      relative contributions of these subunits were alpha2 approximately alpha3>alpha5,
      and thus very similar to those found for intrathecal diazepam (0.09 mg/kg).
      Accordingly, SL-651498 (10mg/kg, p.o.), an "anxioselective" benzodiazepine site
      agonist with preferential activity at alpha2/alpha3 subunits, significantly
      reduced formalin-induced flinching in wild-type mice. We conclude that systemic
      diazepam exerts a genuine antihyperalgesic effect, which depends on spinal
      GABA(A) receptors containing alpha2 and/or alpha3 subunits.

PMID- 19091470
TI  - Characterization of an intracellular cystatin homolog from the tick Haemaphysalis
      longicornis.
AB  - Cystatins are tight-binding inhibitors of papain-like cysteine proteases. On the
      basis of amino acid sequencing, cystatins can be subdivided into three closely
      related families, family 1, family 2 and family 3. Among them, only family 1
      cystatins are intracellular. In this report, a gene encoding family 1 cystatin
      from tick Haemaphysalis longicornis (Hlcyst-1) has been identified. Its full
      length cDNA is 437 bp, including an intact ORF encoding an expected protein with
      98 amino acids. Sequence analysis demonstrated that it has significant homology
      with the known family 1 cystatin. The recombinant protein was expressed in a GST
      fused soluble form in Escherichia coli, and its inhibitory activity against
      papain, cathepsin L, and cathepsin B was identified by fluorogenic substrate
      analysis. This is the first report of an intracellular cystatin homolog from the
      tick H. longicornis.

PMID- 19091471
TI  - Prevalence and age-related infection of Cryptosporidium suis, C. muris and
      Cryptosporidium pig genotype II in pigs on a farm complex in the Czech Republic.
AB  - A total of 413 pig faecal samples were collected from pre-weaners (119), starters
      (131), pre-growers (123) and sows (40) from a farm with a closed breeding system
      segmented into two breeding complexes and a growing complex in the region of
      Vysocina, Czech Republic and screened for the presence of Cryptosporidium using
      staining methods and genotyping (SSU rRNA). Cryptosporidium oocysts were detected
      by microscopy in the faeces of 21.1% of the samples (87/413). Sequence analyses
      and RFLP identified C. suis in 44, Cryptosporidium pig genotype II in 23 and C.
      muris in 2 samples. No mixed infections were found. Pigs under 7 weeks of age
      were infected with C. suis only. Cryptosporidium pig genotype II was found in
      animals from 7 weeks of age. No relationship was found between diarrhoea and any
      Cryptosporidium infection in any of the different age groups (P<0.05). The pre
      weaned pigs shed significantly more Cryptosporidium oocysts than older pigs and
      it was associated with C. suis infection.

PMID- 19091472
TI  - Severe infection of adult dogs with helminths in Hunan Province, China poses
      significant public health concerns.
AB  - The prevalence of helminths in adult dogs was investigated in Hunan Province, the
      People's Republic of China between June 2006 and December 2007. A total of 438
      adult farm dogs slaughtered in local abattoirs from 9 representative
      administrative regions in Hunan Province were examined for the presence of
      helminths using a helminthological approach. All collected worms were counted and
      identified to species according to existing keys and descriptions. A total of 11
      helminth species were found in the dogs, and they represented 2 phyla, 3 classes,
      6 families and 8 genera. All dogs were infected by more than one helminth
      species. Clonorchis sinensis (29.4%) was the only trematode species found,
      Dipylidium caninum (42.3%) was the most common cestode species, and Toxocara
      canis (45.2%) the most common nematode species. 6 of the 11 dog helminths are
      also transmissible to humans (i.e., zoonotic), and can cause severe clinical
      human diseases, posing significant public health threats. The results of the
      present investigation have implications for the ongoing control of helminth
      infections in dogs and humans in Hunan Province, China.

PMID- 19091473
TI  - Prevalence of anti-Toxoplasma gondii and anti-Neospora caninum antibodies in
      sheep from Mossoro, Rio Grande do Norte, Brazil.
AB  - Toxoplasma gondii is an obligate intracellular parasite with a variety of hosts,
      responsible for reproductive problems and economic losses in sheep flocks.
      Neospora caninum was recently identified and its clinical presentation in sheep
      is similar to that of toxoplasmosis, which can cause repeated abortions, though
      less frequently in this species. In order to confirm the prevalence of these
      agents in the city of Mossoro, Rio Grande do Norte, Brazil, 409 serum samples
      from adult sheep (364 females and 45 males) were tested by the indirect
      immunofluorescence antibody test, using cut-off point at a dilution of 1:64 and
      1:50 for T. gondii and N. caninum, respectively. From the 35 properties examined,
      23 (65.7%) had at least one seropositive animal for T. gondii and six (17.1%) for
      N. caninum. The prevalence of seropositive animals for T. gondii was 20.7% and
      for N. caninum 1.8%. There was no association between the presence of the agent's
      antibody and gender, reports of reproductive problems and presence of dogs and/or
      cats in the properties. T. gondii is well distributed and N. caninum has low
      prevalence in sheep and in the properties of the studied region.

PMID- 19091474
TI  - The use of a semiochemical bait to enhance exposure of Amblyomma variegatum
      (Acari: Ixodidae) to Metarhizium anisopliae (Ascomycota: Hypocreales).
AB  - Experiments were conducted to explore the use of a semiochemical bait to enhance
      exposure of Amblyomma variegatum Fabricius (Acari: Ixodidae) to different
      formulations of the entomopathogenic fungus Metarhizium anisopliae (Metsch.)
      Sorok. (Ascomycota: Hypocreales). Initially, the relative efficacies of
      attraction-aggregation-attachment pheromone (AAAP), made up of o-nitrophenol,
      methyl salicylate and nonanoic acid in the ratio 2:1:8, 1-octen-3-ol and butyric
      acid, were evaluated in an olfactometer. Only AAAP and 1-octen-3-ol were found to
      elicit attractive responses to the tick. Simultaneous release of 1-octen-3-ol and
      AAAP together with CO(2) from a trap in semifield plots attracted up to 94.0+/-6%
      of adult ticks from a distance of 6m, and up to 24.0+/-5.1% from 8m. Formulations
      of M. anisopliae (dry powder, oil, and emulsifiable) applied within the trap
      baited with AAAP, 1-octen-3-ol and CO(2) resulted in high levels of contamination
      of the ticks attracted to the traps. However, 48h after autoinoculation, 89.1 and
      33.3% of conidia were lost in dry powder and oil formulations, respectively.
      Emulsifiable formulation showed least loss of propagules (17.1%). Samples of
      ticks attracted to the baited traps were transferred to plastic basins containing
      grass and maintained for 5 weeks. The experiment was conducted in rainy and dry
      seasons. Emulsifiable formulation gave the highest relative tick reduction in
      both seasons: 54.7 and 46.5% in rainy and dry seasons, respectively, followed by
      oil formulation (32.0 and 23.8%) and powder formulation (38.0 and 24.4%).

PMID- 19091475
TI  - Seroprevalence and risk factors of caprine toxoplasmosis in Minas Gerais, Brazil.
AB  - The objective of this work was to carry out a study on caprine toxoplasmosis in
      the state of Minas Gerais, Brazil. To determine the prevalence of toxoplasmosis
      in goats in Minas Gerais, 767 sera from goats were tested by ELISA (enzyme-linked
      immunosorbent assay) and IFAT (indirect fluorescence antibody test). The
      prevalence of antibodies to Toxoplasma gondii was 43.0% and 46.0% by ELISA and
      IFAT, respectively. It was observed that 26.8% of the goats show low-avidity IgG
      to T. gondii. These results suggest the presence of animals in recent phase of
      toxoplasmosis in Minas Gerais. The risk factors for toxoplasmosis in goats were:
      age over 36 months (OR=1.21; IC 95% 1.02-1.44), use of pen (OR=1.83; IC 95%1.01
      3.31) and pure breed animals (OR=2.49; IC 95% 1.11-5.59).

PMID- 19091476
TI  - Identification of antigenic genes in Trichinella spiralis by immunoscreening of
      cDNA libraries.
AB  - Genes encoding antigens of adult worm, newborn larvae and muscle larvae of
      Trichinella spiralis were identified by immunoscreening their corresponding cDNA
      libraries. The cDNA libraries of T. spiralis adult (3 day old, Ad3) and newborn
      larvae (NBL) were screened using the serum of a pig infected with 20,000 muscle
      larvae (ML) at 26 days post-infection (dpi). Fifty-two positive clones
      representing 18 unique genes were obtained from the Ad3 cDNA library. The deduced
      amino acid sequences of 8 cDNAs were sequence homologues of the serine protease
      like protein family. In the screening of NBL cDNA library, 81 positive clones
      representing 8 unique genes were isolated and of these, 70 clones corresponded to
      an NBL stage-specific serine protease gene. The ML cDNA library was screened
      using pig anti-Trichinella serum obtained at 60 dpi and 18 positive clones
      representing 8 unique genes were identified. Ten clones encoded a protein that is
      identical to a T. spiralis serine protease inhibitor. In general, our results
      revealed that antigenic serine protease-like proteins were found during the two
      invasive stages, Ad and NBL when these libraries were screened using 26 dpi
      antiserum, whereas a serine protease inhibitor was found in abundance in the ML
      library when it is screened using 60 dpi antiserum. These data are consistent
      with serine proteases playing an important role during the invasive stages of
      Trichinella infections, but become inhibited or internally controlled when the
      parasite enters a more stable, non-developing environment.

PMID- 19091477
TI  - Prevalence and molecular characterization of bovine Cryptosporidium in Qazvin
      province, Iran.
AB  - The aim of this study was to determine the prevalence, variability with host age,
      and the genotypes of species of Cryptosporidium in cattle from 15 dairy farms in
      Qazvin province, Iran. Fecal samples, collected from 272 cattle during May 2006
      to December 2007, were characterized microscopically. Oocysts from 51 positive
      samples were analyzed using PCR assay of 18S SSU rRNA, restriction fragment
      length polymorphism (RFLP) and sequencing. We identified 72.6% of the positive
      samples as Cryptosporidium parvum, 17.7% as Cryptosporidium andersoni, 7.8% as
      Cryptosporidium bovis and 1.9% as a novel genotype of C. parvum possessing a
      single mutation on MboII restriction. An infection rate of 19.5% of C. parvum
      among 174 pre-weaned calves was significantly higher than the 3.1% among 98 post
      weaned calves (P<0.0006). This is the first report of C. bovis and the new
      subgenotype of C. parvum in Iranian cattle.

PMID- 19091478
TI  - A longitudinal study on morbidity and mortality in youngstock smallholder dairy
      cattle with special reference to tick borne infections in Tanga region, Tanzania.
AB  - The incidence and potential determinants of tick borne diseases (TBDs) were
      estimated in a longitudinal study that was conducted in cohorts of youngstock
      animals of less than 3 years kept in smallholder dairy farms in Tanga region,
      Tanzania. A combination of serological tests, blood and lymph node smears were
      used as diagnostic tests for TBDs during the study. A total number of 549
      youngstock were followed for a total of 532.2 animal years from August 1999 to
      July 2001. Overall morbidity and mortality rates (due to all causes) were 8.26
      and 12.0 per 100 animals year at risk, respectively. Of the total deaths, 56%
      were attributed to TBDs (37.5%-East Coast fever (ECF) and 18%-anaplasmosis).
      Specific morbidity and mortality rates for ECF were estimated to be 3.57 and 4.51
      per 100 animals year risk, respectively, and for anaplasmosis 2.21 and 2.25 per
      100 animals year risk, respectively. Analysis of survival times to death
      indicated that calves < 6 months of age and those out on pasture had higher death
      rates than older calves and those kept under zero-grazing systems (relative risk
      [RR] 3.80, P = 0.001 for pasture-grazed calves). There was no mortality or
      morbidity arising specifically from cowdriosis (heartwater) or babesiosis during
      the whole period of monitoring. The study revealed that most farms were applying
      under strength acaricide and using acaricides at irregular intervals. It is
      concluded that TBDs namely ECF and anaplasmosis are important diseases in this
      farming system and reducing morbidity and mortality in smallholder dairy farms in
      Tanga region is an achievable goal. Both farmers and extension services should
      target at risk calves with the provision of both strict tick control and optimal
      husbandry management practices.

PMID- 19091479
TI  - Acaricidal effects of the essential oil of Origanum minutiflorum (Lamiaceae)
      against Rhipicephalus turanicus (Acari: Ixodidae).
AB  - The acaricidal effects of the volatile essential oil Origanum minutiflorum O.
      Schwarz & P.H. Davis (Lamiaceae) against adult Rhipicephalus turanicus was
      evaluated at a variety of concentrations and exposure times. Generally tick
      mortality increased with concentration and exposure. Ticks exposed to vapors from
      cotton wicks containing at least 10mul/L resulted in complete (100%) mortality at
      120min. The major constituent of essential oil obtained from the plant material
      of O. minutiflorum was carvacrol.

PMID- 19091480
TI  - Characterization of the immune response of domestic fowl following immunization
      with proteins extracted from Dermanyssus gallinae.
AB  - Dermanyssus gallinae is the most significant ectoparasite of European poultry egg
      laying production systems due to high costs of control and associated production
      losses as well as adverse effects on bird welfare. In this study, soluble
      proteins were extracted from unfed D. gallinae (DGE) using a urea-based detergent
      and ultra-filtration, passed through a 0.22 microm filter and blended aseptically
      with adjuvant. One group of laying hens was immunized with DGE and adjuvant
      (Montanide ISA 50 V) whilst another group (Control) received physiological saline
      and adjuvant. All birds were immunized on two occasions, 21 days apart. Antibody
      response to immunization was determined by ELISA and western blotting using
      immunoglobulins (Igs) extracted from egg yolk. DGE immunization of hens resulted
      in a significant (P<0.05) IgY response compared to controls, although there was
      no significant difference in IgM response between treatments. A number of
      proteins were identified by western blotting using IgY antibodies from DGE
      immunized birds, most prominently at 40 and 230kDa. Analysis of proteins from
      approximately corresponding bands on SDS-PAGE confirmed the identity of
      tropomyosin, whilst other proteins showed high sequence homology with myosin and
      actin from other arachnid and insect species. Immunization of hens with DGE
      resulted in a 50.6% increase in mite mortality (P<0.001) 17h after feeding when
      tested by an in vitro mite feeding model. Data in this study demonstrate that
      somatic antigens from D. gallinae can be used to stimulate a protective immune
      response in laying hens. Further work is needed to identify other proteins of
      interest that could confer higher protection against D. gallinae, as well as
      optimization of the vaccination and in vitro testing protocol.

PMID- 19091481
TI  - Bacteria form biofilms against cancer metastasis.

PMID- 19091482
TI  - Bicycle riding may cause erectile dysfunction.

PMID- 19091483
TI  - The possible process of neovascularization in degeneration intervertebral disc.

PMID- 19091484
TI  - Why we should treat idiopathic optic neuritis with high-dose and long-term
      corticosteroids in China.

PMID- 19091485
TI  - The relevance of somatic treatments in psychoses.

PMID- 19091486
TI  - Regarding the most recent common ancestor of HIV-1 Group M.

PMID- 19091487
TI  - Lymphohistiocytic anaplastic large cell lymphoma involving skin: a diagnostic
      challenge.
AB  - Systemic anaplastic large cell lymphoma (ALCL) involving the skin should be
      differentiated from primary cutaneous CD30-positive T-cell lymphoproliferative
      disorders. The lymphohistiocytic variant of ALCL (LH-ALCL) is rich in reactive
      histiocytes with relatively few neoplastic cells, which pose a diagnostic
      challenge. We present a case of LH-ALCL involving skin mimicking granulomatous
      inflammation. A 30-year-old woman presented with cervical lymphadenopathy and
      multiple non-tender, non-itching, erythematous papules over the neck, chest, and
      abdomen. Biopsy of the cervical lymph node showed LH-ALCL with null cell
      phenotype. Microscopically, the cutaneous lesion was located predominately around
      the hair follicle, with numerous reactive histiocytes and scanty medium-sized
      lymphoma cells expressing CD30 and anaplastic lymphoma kinase (ALK) protein.
      Furthermore, an ALK gene rearrangement was demonstrated by locus-specific
      interphase fluorescent in situ hybridization, confirming cutaneous involvement
      with LH-ALCL. LH-ALCL involving the skin is a rare event, and the numerous
      reactive histiocytes may mask scanty tumor cells. In addition to B-and T-cell
      markers, (dermato) pathologists must be aware of this entity in cutaneous
      lymphohistiocytic proliferations and perform immunostaining for CD30 and ALK to
      reach a correct diagnosis.

PMID- 19091489
TI  - [A first (crucial?) step toward the acceptance of using vaginal prosthetic
      reinforcement implants].

PMID- 19091488
TI  - The association of mast cell density with myometrial invasion in endometrial
      carcinoma: a preliminary report.
AB  - It is known that cancer is not a single transformational event. It is rather a
      multistage process involving complex interactions with the surrounding cellular
      microenvironment. Mast cells accumulate at sites of tumor growth in response to
      numerous chemoattractants. Our aim was to investigate the relationship between
      mast cell density (MCD) and myometrial invasion in endometrial carcinomas.
      Immunohistochemistry was performed on 35 unselected consecutive hysterectomy
      specimens from patients with endometrial adenocarcinoma. C-kit-positive mast cell
      assessment was performed in the myometrium adjacent to tumor tissue. A mean
      number of <or=15 mast cells per high power field (HPF) were regarded as low mast
      cell density (L-MCD), and a count of >or=16 mast cells was regarded as high mast
      cell density (H-MCD). A significant correlation (p=0.018, Pearson Chi-Square
      test) between H-MCD and the presence of myometrial invasion was demonstrated in
      endometrial carcinomas. H-MCD was found in 54% of all cases, and 94% of H-MCD
      cases had myometrial invasion, suggesting a role of mast cells or an interaction
      with tumor. Therapeutic modalities orientated to these cells or their
      microenvironment as a new target for adjuvant treatment might determine the
      prognosis in endometrial carcinomas.

PMID- 19091490
TI  - Prevalence, timing, and predictors of transitions from inhalant use to inhalant
      use disorders.
AB  - BACKGROUND: Few studies of the natural history of DSM-IV inhalant substance use
      disorders (I-SUDs) have been conducted. This investigation examined the
      prevalence, timing, and predictors of transitions from inhalant use to formal I
      SUDs among inhalant users within a nationally representative sample. METHODS:
      Participants were 664 U.S. residents participating in the 2000-2001 National
      Epidemiologic Survey on Alcohol and Related Conditions who reported lifetime
      inhalant use. Respondents completed structured interviews assessing DSM-IV
      psychiatric/substance use disorders. Bivariate and Cox regression analyses were
      conducted to identify risk factors for transitions from inhalant use to I-SUDs.
      RESULTS: Nearly one in five (19.4%) persons initiating inhalant use developed an
      I-SUD. Most I-SUD transitions were to inhalant abuse rather than inhalant
      dependence. Risk for development of I-SUDs was greatest in the first year
      following initiation of inhalant use and low thereafter. Multivariate
      proportional hazards models indicated that presence of a mood/anxiety disorder
      (HR=7.7, CI=3.1-18.9) or alcohol use disorder (HR=11.9, CI=5.46-26.00) antedating
      initiation of inhalant use predicted significantly elevated risk for I-SUDs,
      whereas being married conferred a lower risk for onset of I-SUDs. CONCLUSIONS: I
      SUDs were relatively common among inhalant users, generally occurred in the year
      following initiation of inhalant use, and were associated with early-onset
      mood/anxiety and alcohol use disorders. Given the young average age at onset of
      inhalant use and the rapidity with which most I-SUDs developed, interventions
      directed to adolescents who have initiated inhalant use might be effective in
      reducing the proportion of inhalant users who develop I-SUDs.

PMID- 19091491
TI  - Molecular characterization of two different strains of haemotropic mycoplasmas
      from a sheep flock with fatal haemolytic anaemia and concomitant Anaplasma ovis
      infection.
AB  - After the first outbreak of fatal Mycoplasma ovis infection (eperythrozoonosis)
      in a sheep flock in Hungary (1997), a second wave of the disease was noted in
      2006, with different seasonal pattern and affected age group, as well as
      increased mortality (5.5%). The aim of the present study was to molecularly
      characterize the causative agent and to reveal underlying factors of the second
      wave of the disease. Remarkably, among the 33 sheep examined, 17 were infected
      with two strains of haemotropic mycoplasmas. Cloning and sequencing isolates of
      the latter showed that one of the strains was 99.4-99.8% identical to M. ovis
      (AF338268), while the second was only 96.8-97.9% identical and contained a 17-bp
      deletion. Different isolates of both strains were demonstrated in the same
      animal. When analyzing possible risk factors for fatal disease outcome, we found
      that among sheep born prior to the 1997 outbreak significantly more animals
      survived the second outbreak than succumbed to disease. In addition, locally born
      sheep were less frequently diseased than sheep introduced into the flock from
      other places. This suggests an immunoprotective effect in some animals.
      Concurrent infection with Anaplasma ovis was detected in 24 of the 33 evaluated
      sheep. In conclusion, this is the first study to demonstrate the existence of and
      characterize two genetically distinct ovine haemotropic mycoplasma strains in a
      sheep flock with fatal haemolytic anaemia.

PMID- 19091492
TI  - Occurrence and transmission of Newcastle disease virus aerosol originating from
      infected chickens under experimental conditions.
AB  - In order to better understand airborne transmission of Newcastle disease, a model
      system was established and two trials were conducted. Twenty-five principal
      specific pathogen free (SPF) chickens were inoculated with NDV and were housed in
      one isolator. 6 days after the chickens were challenged, 15 chickens were placed
      into another isolator which received its air supply from the first isolator. The
      NDV aerosol originating from inoculated chickens was collected with All Glass
      Impinger-30 (AGI-30) to study the occurrence and concentration of NDV aerosol.
      The antibody response to infection was assessed by the hemagglutination
      inhibition (HI) test and viral shedding was detected by RT-PCR and Dot-ELISA. NDV
      aerosol was initially detectable by RT-PCR and cell culture at day 2 or 3 post
      inoculation (dpi). The aerosol concentration peaked at 1.69x10(4)PFU/m(3) air at
      13dpi in trial 1, 9.14x10(3)PFU/m(3) air at 11dpi in trial 2 and was consistently
      detectable up to 40dpi. NDV shedding was detectable from 2 to 40dpi of inoculated
      chickens and from 6 days post-aerosol exposed infection (dpi) to 33dpi of aerosol
      exposed chickens. The viral strain induced high antibody level, both in
      inoculated and in aerosol exposed chickens. Airborne transmission did occur, as
      shown by NDV shedding and seroconversion to NDV in aerosol exposed chickens. The
      results indicated that viruses shed from infected chickens readily aerosolized
      and airborne transmission of NDV was possible.

PMID- 19091493
TI  - Real-time PCR, compared to liquid and solid culture media and ELISA, for the
      detection of Mycobacterium avium ssp. paratuberculosis.
AB  - A goal of Johne's disease control programs is to accurately detect Mycobacterium
      avium ssp. paratuberculosis (MAP) infected cattle as quickly as possible to
      reduce disease transmission. A newly introduced real-time PCR provides results
      rapidly, but its accuracy in the field has not been evaluated. Fecal and serum
      samples collected from dairy cows in northern Indiana were used to estimate the
      sensitivity and specificity of a newly licensed real-time PCR test for direct
      fecal detection of Mycobacterium avium ssp. paratuberculosis (MAP). Results of
      the real-time PCR were evaluated in parallel with solid and liquid media culture
      systems and a serum ELISA for detection of MAP antibodies to determine the
      accuracy of the real-time PCR and the tests' potential usefulness in the field. A
      total of 143 samples were tested by all four methods. Using prior published
      estimates for sensitivity and specificity of each of the tests and Bayesian
      methodology, the sensitivity and specificity of the real-time PCR test was
      estimated to be 0.60 and 0.97, respectively. The accuracy of real-time PCR (0.90)
      was comparable to both solid (0.91) and liquid (0.93) culture. Because real-time
      PCR accuracy is comparable to standard culture methods, it is a useful new test.
      In addition, test results are obtained as rapidly as an ELISA, but are more
      accurate than the ELISA (0.82). This makes real-time PCR an attractive test and
      should shorten the quarantine period required for new purchases of unknown MAP
      status animals into herds participating in an MAP control program.

PMID- 19091495
TI  - Effect of birth weight and postnatal weight gain on body composition in early
      infancy: The Generation R Study.
AB  - BACKGROUND: Rapid postnatal weight gain is associated with obesity and type 2
      diabetes in later life. The influence of rapid weight gain on body composition in
      early infancy is still unknown and the critical periods of weight gain for later
      disease are debated. AIMS: To investigate the effect of birth weight and rapid
      weight gain on body composition in the first 6 months of life. STUDY DESIGN: The
      Generation R Study, a population-based prospective cohort study from fetal life
      onwards. SUBJECTS AND OUTCOME MEASURES: We measured body fat and fat distribution
      by skinfold thickness at the age of 6 weeks and 6 months in 909 Dutch term
      infants. Analyses were adjusted for current body mass index, sex and maternal
      socioeconomic status, pre-pregnancy body mass index, height and duration of
      breastfeeding. RESULTS: Upward postnatal weight percentile change was associated
      with increased skinfold thickness, percentage body fat at 6 weeks and 6 months
      and a larger truncal/peripheral fat ratio at 6 months (p<0.01 for all). Birth
      weight was inversely associated with truncal/peripheral fat ratio (p<0.01) but
      not with relative body fat at 6 months. CONCLUSION: During early postnatal rapid
      weight gain infants do not grow in all body tissues in equal measure. Instead,
      they acquire relatively large amounts of fat, which is preferentially distributed
      to the truncal region. Long term observational studies have to assess if such
      changes in body composition persist into adulthood.

PMID- 19091494
TI  - Characterization of fecal microbiota from a Salmonella endemic cattle herd as
      determined by oligonucleotide fingerprinting of rDNA genes.
AB  - The gastrointestinal (GI) tract microbiota is composed of complex communities.
      For all species examined thus far, culture and molecular analyses show that these
      communities are highly diverse and individuals harbor unique consortia. The
      objective of the current work was to examine inter-individual diversity of cattle
      fecal microbiota and determine whether Salmonella shedding status correlated with
      community richness or evenness parameters. Using a ribosomal gene array-based
      approach, oligonucleotide fingerprinting of ribosomal genes (OFRG), we analyzed
      1440 16S genes from 19 fecal samples obtained from a cattle herd with a history
      of salmonellosis. Identified bacteria belonged to the phyla Firmicutes (53%),
      Bacteroidetes (17%), and Proteobacteria (17%). Sequence analysis of 16S rDNA gene
      clones revealed that Spirochaetes and Verrucomicrobia were also present in the
      feces. The majority of Firmicutes present in the feces belonged to the order
      Clostridiales, which was verified via dot blot analysis. beta-Proteobacteria
      represented 1.5% of the bacterial community as determined by real-time PCR.
      Statistical analysis of the 16S libraries from the 19 animals indicated very high
      levels of species richness and evenness, such that individual libraries
      represented unique populations. Finally, this study did not identify species that
      prevented Salmonella colonization or resulted from Salmonella colonization.

PMID- 19091496
TI  - Studies on morphological features of foetal and adult ovaries in Kano brown
      goats.
AB  - In this work we studied the structures of 51 foetal and 14 adult ovaries obtained
      from slaughtered Kano brown does in Nsukka abattoir. The ages of the adult does
      were determined by dentition and foetuses by crown rump length method. The foetal
      and adult ovaries were divided into five different groups using specific age
      intervals as Gestation day (GD) 50-65, 66-95, 96-125 and 126-145 and adults. For
      histological studies the ovaries were fixed, processed and routinely stained with
      H&E. The ovarian follicles were classified into 5 types according to granulosa
      cell layers surrounding the oocytes. The number of ovarian follicles per
      microscopic field, number of granulosa cells surrounding type 1 and 1A follicles
      and diameter of the ovarian follicles were determined for each group at 400x
      magnification. Grossly the foetal ovaries were like pin head, oval in shape,
      uniformly smooth and creamy in colour. The adult ovaries had follicles with
      different sizes. The adult mean ovarian weights were significantly higher
      (P<0.01) than those of the foetuses. Microscopically, the GD 50-65 ovaries had no
      distinct cortex and medulla. Oogonia were numerous among other stromal cells
      toward the periphery of the ovary. By GD 66-95 the ovaries contained types 1, 1a,
      2 and 3 follicles. GD 96-125 ovaries contained type 4 follicles with early antrum
      formation and those of GD 126-145 comprised type 5 among other follicles. The
      adult ovaries comprised all the ovarian follicle types. The number of type 1
      follicles increased significantly (P<0.01) with foetal age. It was least in the
      adults. The diameter of adult follicles was significantly higher (P<0.01) than
      those of the foetuses. This result provides baseline information on the
      morphological development of ovaries in Kano brown goats.

PMID- 19091497
TI  - Progesterone, progestogens and psychosomatic health of the climacteric woman.
AB  - Psychosomatics as a medical perspective and discipline focuses on the interaction
      of physical and mental health in a specific life situation of a patient, taking
      into account the physical and emotional wellbeing, role functioning, satisfaction
      with the partner and family relationship, as well as sexual function and
      satisfaction. The role of progesterone for the psychosomatic health of the
      climacteric woman depends on the individual symptom cluster and the pre-existing
      receptivity of the progesterone receptors which are widely distributed in the
      body and especially the brain of the woman. The complex action and interaction of
      progesterone is reflected in controversial empirical results about the impact of
      progesterone on the physical, mental and sexual health of climacteric women. From
      biological rationale and clinical experience there are however two important
      effects of P on the combined physical, mental and sexual wellbeing of climacteric
      patient: the antiestrogenic effect of progesterone is important on the peripheral
      physical level not only to protect the endometrium against overstimulation but
      also to reduce the individual suffering from heavy bleeding, breast tension,
      bloating and general discomfort. The positive anxiolytic and sedative effects of
      progesterone on the central nervous system depend on the type of progestogen, the
      dosage, the timing of application, the combination with estrogen etc. It can be
      concluded that progesterone and progestogens have an important potential to
      maintain or improve the psychosomatic health of the climacteric women. Their use
      must however be tailored to specific symptom clusters and to the individual's pre
      existing psychosomatic health status.

PMID- 19091498
TI  - A comparison of hair colour measurement by digital image analysis with reflective
      spectrophotometry.
AB  - While reflective spectrophotometry is an established method for measuring
      macroscopic hair colour, it can be cumbersome to use on a large number of
      individuals and not all reflective spectrophotometry instruments are easily
      portable. This study investigates the use of digital photographs to measure hair
      colour and compares its use to reflective spectrophotometry. An understanding of
      the accuracy of colour determination by these methods is of relevance when
      undertaking specific investigations, such as those on the genetics of hair
      colour. Measurements of hair colour may also be of assistance in cases where a
      photograph is the only evidence of hair colour available (e.g. surveillance).
      Using the CIE L(*)a(*)b(*) colour space, the hair colour of 134 individuals of
      European ancestry was measured by both reflective spectrophotometry and by
      digital image analysis (in V++). A moderate correlation was found along all three
      colour axes, with Pearson correlation coefficients of 0.625, 0.593 and 0.513 for
      L(*), a(*) and b(*) respectively (p-values=0.000), with means being significantly
      overestimated by digital image analysis for all three colour components (by an
      average of 33.42, 3.38 and 8.00 for L(*), a(*) and b(*) respectively). When using
      digital image data to group individuals into clusters previously determined by
      reflective spectrophotometric analysis using a discriminant analysis, individuals
      were classified into the correct clusters 85.8% of the time when there were two
      clusters. The percentage of cases correctly classified decreases as the number of
      clusters increases. It is concluded that, although more convenient, hair colour
      measurement from digital images has limited use in situations requiring accurate
      and consistent measurements.

PMID- 19091499
TI  - A fatal poisoning involving Bromo-Dragonfly.
AB  - This paper reports a fatal overdose case involving the potent hallucinogenic drug
      Bromo-Dragonfly (1-(8-bromobenzo[1,2-b; 4,5-b']difuran-4-yl)-2-aminopropane). In
      the present case, an 18-year-old woman was found dead after ingestion of a
      hallucinogenic liquid. A medico-legal autopsy was performed on the deceased,
      during which liver, blood, urine and vitreous humour were submitted for
      toxicological examination. Bromo-Dragonfly was identified in the liver blood
      using UPLC-TOFMS, and was subsequently quantified in femoral blood (0.0047
      mg/kg), urine (0.033 mg/kg) and vitreous humour (0.0005 mg/kg) using LC-MS/MS.
      Calibration standards were prepared from Bromo-Dragonfly isolated from a bottle
      found next to the deceased. The structure and purity of the isolated compound
      were unambiguously determined from analysis of UPLC-TOFMS, GC-MS, HPLC-DAD, (1)H
      and (13)C NMR data and by comparison to literature data. The autopsy findings
      were non-specific for acute poisoning. However, based on the toxicological
      findings, the cause of death was determined to be a fatal overdose of Bromo
      Dragonfly, as no ethanol and no therapeutics or other drugs of abuse besides
      Bromo-Dragonfly were detected in the liver, blood or urine samples from the
      deceased. To our knowledge, this is the first report of quantification of Bromo
      Dragonfly in a biological specimen from a deceased person. This case caused the
      drug to be classified as an illegal drug in Denmark on 5th December 2007.

PMID- 19091500
TI  - High postnatal oxidative stress in neonatal cystic periventricular leukomalacia.
AB  - Oxidative stress plays an important role in cystic periventricular leukomalacia
      (PVL). We performed a case-control study of preterm infants delivered at <35
      weeks of gestation between January 2003 and December 2006. Patients were
      stratified into three groups, according to age at which cysts were initially
      identified: 10 days old (early cystic PVL; n=10), >10 days old (late cystic PVL;
      n=12); and no cystic PVL (controls; n=22). Serum total hydroperoxide, biological
      antioxidant potential and oxidative stress index (calculated as total
      hydroperoxide/biological antioxidant potential) were measured within 3h after
      birth. Frequencies of preterm rupture of membrane and chorioamnionitis were
      significant higher in early cystic PVL than in late cystic PVL or controls.
      Duration of oxygen treatment and mechanical ventilation and frequency of apnea
      were significantly higher in late cystic PVL than in controls or early cystic
      PVL. Serum total hydroperoxide levels and oxidative stress index were
      significantly higher in early cystic PVL than in late cystic PVL or controls
      (p<0.05, respectively). Postnatal duration until cyst identification displayed a
      significant negative correlation with oxidative stress index and total
      hydroperoxide level (r=-0.497, p<0.05; r=-0.50, p<0.05, respectively). These
      findings suggest that early onset of cystic PVL might be due to either antenatal
      or intrapartum factors, but late onset might be due to postnatal factors. In the
      pathophysiology and therapy of cystic PVL, oxidative stress and onset timing
      appear crucial. This is the first study to reveal that neonates experiencing much
      more oxidative stress at birth show earlier onset of cystic PVL.

PMID- 19091501
TI  - Transgenerational hormonal imprinting caused by vitamin A and vitamin D treatment
      of newborn rats. Alterations in the biogenic amine contents of the adult brain.
AB  - Biogenic amines (norepinephrine, dopamine, homovanillic acid, serotonin and 5
      hyroxyindole acetic acid) were measured by HPLC method in adult F1 generation
      rats' brain regions (brainstem, hypothalamus, hippocampus, striatum and frontal
      cortex), whose mothers (P generation) were treated with vitamin A or vitamin D
      neonatally (hormonal imprinting). Many significant differences were found,
      related to the maternally untreated controls. In the earlier studied P generation
      females, vitamin A consistently influenced the serotonerg system (5HIAA), while
      vitamin D the dopaminerg system (DA or HVA). Vitamin A imprinting always resulted
      in reduced, while that by vitamin D always in increased tissue levels. In the
      present case (directly untreated F1 generation) the transgenerational effect was
      not unidirectional, however biogenic amine tissue levels were strongly disturbed
      and brain-area dependent. The results call attention to the transgenerational
      effect of hormonal imprinting in the case of receptor level acting vitamins which
      are frequently used in the most imprinting-sensitive period (perinatally) of
      human life and suggests that caution is warranted.

PMID- 19091502
TI  - Heated lipiodol as an embolization agent for transhepatic arterial embolization
      in VX2 rabbit liver cancer model.
AB  - PURPOSE: To evaluate the therapeutic effect of heated (60 degrees C) lipiodol via
      hepatic artery administration in a rabbit model of VX2 liver cancer. MATERIALS
      AND METHODS: Thirty male New Zealand white rabbits were randomly divided into
      three groups with 10 rabbits assigned to each group. VX2 carcinoma cells were
      surgically implanted into the left hepatic lobe. The tumors were allowed to grow
      for 2 weeks, and studies were performed until the diameter of the tumors detected
      by ultrasonograph reached 2-3cm. Under anesthesia, trans-catheter hepatic
      arterial embolization was performed and doxorubicin-lipiodol (37 degrees C)
      (1mL), lipiodol (60 degrees C) (1mL) or control (physiological saline (37 degrees
      C) (1mL)) solution was injected into the hepatic arteries of animals in the three
      groups. One week later, the volume of the tumor was measured by ultrasonograph
      again. The serum of all rabbits was collected before injection and at 4 and 7
      days after injection, and the level of aspartate aminotransferase (AST) was
      checked. The survival period of the three groups of rabbits after treatment was
      also recorded. During the last course of their disease, the rabbits were given
      analgesics to relieve suffering. RESULTS: The tumor growth rate in the lipiodol
      (60 degrees C) group (0.92+/-0.21, tumor volume from 1811+/-435 to 1670+/
      564mm(3)) was significantly lower than that in the control group (3.48+/-1.17,
      tumor volume from 1808+/-756 to 5747+/-1341mm(3)) (P<0.05) and in the doxorubicin
      lipiodol (37 degrees C) group (1.69+/-0.26, tumor volume from 1881+/-641 to
      2428+/-752mm(3)) (P<0.05). Consequently, the survival period of the animals in
      the lipiodol (60 degrees C) group (41.0+/-3.0 days) was significantly greater
      than that in the doxorubicin-lipiodol (37 degrees C) group (38.0+/-2.5 days)
      (P<0.05). On the other hand, there was no statistically significant difference in
      serum AST levels between the lipiodol (60 degrees C) group (148.2+/-11.3UL(-1))
      and the doxorubicin-lipiodol (37 degrees C) group (139.7+/-12.3UL(-1)) (P>0.05).
      However, the serum AST level in the lipiodol (60 degrees C) group was
      significantly higher at 4 days after injection (P<0.05) than in the control group
      (68.6+/-6.6UL(-1)). CONCLUSIONS: Treatment with lipiodol (60 degrees C) resulted
      in an effect on serum AST levels similar to that caused by treatment with
      doxorubicin-lipiodol (37 degrees C). Thus, lipiodol (60 degrees C) treatment
      could greatly prolong the survival period of rabbits with VX2 cancer by
      inhibiting tumor growth.

PMID- 19091503
TI  - Comparison between two-point and four-point methods for quantification of
      apparent diffusion coefficient of normal liver parenchyma and focal lesions.
      Value of normalization with spleen.
AB  - PURPOSE: To compare two quantification techniques of apparent diffusion
      coefficient (ADC), both in normal liver parenchyma and focal lesions, and to
      investigate any potential value of normalization. MATERIALS AND METHODS: Fifty
      six consecutive patients underwent MRI examination of the liver, including a
      single shot spin-echo echo planar imaging diffusion sequence with four b-values
      (0, 50, 500 and 1000s/mm(2)). ADC maps were reconstructed based on a two-point
      method (b-values: 500 and 1000s/mm(2)) and a four-point method (b-values: 0, 50,
      500 and 1000s/mm(2)). Comparison of absolute ADC measurements of the liver,
      benign and malignant focal lesions was performed between the two- and four-point
      techniques. The same analysis was done on normalized ADC values (absolute ADC
      values divided by spleen ADC values). RESULTS: The difference between mean two
      point and four-point ADC values of normal liver (absolute: 1.237x10(-3),
      1.615x10(-3)mm(2)/s, normalized: 1.40, 1.52, respectively) was statistically
      significant (p<0.0001 and p=0.0061). Significantly higher absolute ADC values of
      benign and malignant lesions were recorded with the four-point method (2.860x10(
      3) and 1.307x10(-3)mm(2)/s) over the two-point method (2.243x10(-3), and
      1.011x10(-3)mm(2)/s) (p<0.0001 in both) while the same differences in normalized
      values were proven statistically non-significant for benign lesions (p=0.788) and
      statistically significant for malignant lesions (p=0.015). Both differences in
      absolute and normalized ADC values of benign versus malignant lesions based on
      two- and four-point methods were found to be significant (p<0.0001). CONCLUSION:
      ADC quantification of the liver may be performed with a two-point method (b
      values of 500 and 1000s/mm(2)), while normalization of ADC measurements with the
      spleen is not further improving lesion characterization.

PMID- 19091504
TI  - Whole body MR imaging in neurofibromatosis type 1.
AB  - OBJECTIVE: To assess the value of whole body MR imaging in patients with
      neurofibromatosis type 1 (NF1). MATERIALS AND METHODS: 24 patients (15-59 years;
      mean and median 36 years; 7 males; 17 females) with genetically proven
      neurofibromatosis type 1 were examined with whole body MR imaging. Axial and
      coronal T1- and fat-suppressed T2-weighted images (slice thickness 6-12 mm) were
      acquired on a 1.5T MR unit (Symphony; Siemens, Erlangen, Germany). The images
      were reviewed by 2 radiologists: 1 senior, 1 junior. The criterion for a
      neurofibroma was a mass lesion with low signal intensity on T1 and high signal
      intensity on T2, along the course of a nerve. The location, size, general
      morphology and course along plexuses and nerves were evaluated. Cutaneous and
      subcutaneous neurofibromas were defined as "superficial" neurofibromas. The other
      neurofibromas were regarded as "deep" neurofibromas. RESULTS: There were no major
      problems to differentiate neurofibromas from lymph nodes, vessels or cysts. The
      latter three were easily recognised by their typical shape and location, whereas
      neurofibromas occurred in regions where no mass lesion was anatomically expected.
      There was no relation between age and total number of neurofibromas throughout
      the body. Classification according to location and number of neurofibromas: 8
      patients had only superficial neurofibromas, 1 only deep and 15 both superficial
      and deep lesions. Twelve patients had less than 15 neurofibromas and 12 had more.
      Classification according to course: in 8 patients the neurofibromas occurred
      along plexuses or proximal part of the intercostal nerves; in 16 patients the
      lesions were more peripheral. Classification according to morphology: 4 patients
      had plexiform neurofibromas and 20 patients had multiple solitary lesions. Twelve
      of these 20 patients had less than 15 lesions, and 8 had more. In 2 patients
      multiple solitary neurofibromas occurred along the nerve in a chain
      configuration. In one patient a clinically unsuspected brain tumour was found.
      CONCLUSION: Whole body MR imaging is a reliable method to evaluate the
      distribution, size and morphology of neurofibromas in patients with NF1.

PMID- 19091505
TI  - Cine-MRI swallowing evaluation after tongue reconstruction.
AB  - OBJECTIVE: To determine the feasibility of cine-MRI for non-invasive swallowing
      evaluation after surgery for lingual carcinoma with reconstruction using
      microvascular free flaps. METHODS: Ten patients with stage IV carcinoma of the
      mobile tongue and/or tongue base treated by surgical resection and reconstruction
      with a free flap were evaluated after an average of 4.3 years (range: 1.5-11
      years), using cine-MRI in "single-shot fast spin echo" (SSFSE) mode. Fiberoptic
      laryngoscopy of swallowing was performed before MRI to detect aspiration. The
      tolerance and ability to complete the exam were noted. The mobilities of the oral
      and pharyngeal structures visualized were evaluated as normal, reduced or
      increased. RESULTS: Cine-MRI was well tolerated in all cases; "dry" swallow was
      performed for the 2 patients with clinical aspiration. Tongue base-pharyngeal
      wall contact was observed in 5 cases. An increased anterior tongue recoil,
      increased mandibular recoil, increased posterior oropharyngeal wall advancement
      and an increased laryngeal elevation were observed in 4 cases. One case of a
      passive "slide" mechanism was observed. CONCLUSIONS: Cine-MRI is a safe, non
      invasive technique for the evaluation of the mobility of oral and oropharyngeal
      structures after free-flap reconstruction of the tongue. For selected cases, it
      may be complementary to clinical examination for evaluation of dysphagia after
      surgery and free-flap reconstruction. Further technical advances will be
      necessary before cine-MRI can replace videofluoroscopy, however.

PMID- 19091506
TI  - Radiology as part of an objective structured clinical examination on clinical
      skills.
AB  - INTRODUCTION: An objective structured clinical examination (OSCE) assesses
      clinical competence in a standardised and context related manner. Compared with
      written tests, OSCE's are more susceptible to reliability errors because of the
      use of multiple cases and multiple examiners. In the pre-clinical phase of the
      medical curriculum of the University Medical Centre Utrecht, an OSCE is organised
      as a medical consult. We evaluated the radiology station. METHOD: Four questions
      were formulated: We analysed the OSCE results of second year medical students in
      2004. RESULTS: Two hundred and sixty-five students were examined in the OSCE in
      2004. Ninety-three Students were examined in the radiology station. Cronbach's
      alpha coefficient for the radiology station was 0.92. The average score for the
      radiology station was 3.8 (0.87). The average score for the test without
      radiology was 3.9 (0.32). The range of the average scores for the six different
      cases was 0.5 (3.6-4.1). The range of the average scores for the five examiners
      was 1.0 (3.3-4.3). CONCLUSION: The internal consistency of the items in the
      radiology station is good. The average score for the radiology station is similar
      to that of the other stations. The range of the scores between the different
      cases was relatively small. The range of the scores between the different
      examiners was clearly larger.

PMID- 19091507
TI  - Community composition of ammonia-oxidizing bacteria and archaea in rice field
      soil as affected by nitrogen fertilization.
AB  - Little information is available on the ecology of ammonia-oxidizing bacteria
      (AOB) and archaea (AOA) in flooded rice soils. Consequently, a microcosm
      experiment was conducted to determine the effect of nitrogen fertilizer on the
      composition of AOB and AOA communities in rice soil by using molecular analyses
      of ammonia monooxygenase gene (amoA) fragments. Experimental treatments included
      three levels of N (urea) fertilizer, i.e. 50, 100 and 150 mgNkg(-1) soil. Soil
      samples were operationally divided into four fractions: surface soil, bulk soil
      deep layer, rhizosphere and washed root material. NH(4)(+)-N was the dominant
      form of N in soil porewater and increased with N fertilization. Cloning and
      sequencing of amoA gene fragments showed that the AOB community in the rice soil
      consisted of three major groups, i.e. Nitrosomonas communis cluster, Nitrosospira
      cluster 3a and cluster 3b. The sequences related to Nitrosomonas were
      predominant. There was a clear effect of N fertilizer and soil depth on AOB
      community composition based on terminal restriction fragment length polymorphism
      fingerprinting. Nitrosomonas appeared to be more abundant in the potentially oxic
      or micro-oxic fractions, including surface soil, rhizosphere and washed root
      material, than the deep layer of anoxic bulk soil. Furthermore, Nitrosomonas
      increased relatively in the partially oxic fractions and that of Nitrosospira
      decreased with the increasing application of N fertilizer. However, AOA community
      composition remained unchanged according to the denaturing gradient gel
      electrophoresis analyses.

PMID- 19091508
TI  - Characterization of polymethoxylated flavones in Fructus aurantii by off-line two
      dimensional liquid chromatography/electrospray ionization-ion trap mass
      spectrometry.
AB  - Off-line two-dimensional reversed-phase liquid chromatography (2D-RPLC) coupled
      to electrospray ionization-ion trap mass spectrometry (ESI-ITMS) was operated in
      positive mode (PI) to characterize polymethoxylated flavonoids (PMFs) in
      botanical sample. The fragments of [M+H-nx15](+) produced by loss of one or more
      methyl group from the protonated molecules, as well as [M+H-14](+), [M+H-29](+),
      [M+H-33](+), [M+H-43](+), [M+H-46](+) and [M+H-61](+) fragments formed the
      multiple MS (MS(n)) "fingerprint" of PMFs. 42 target compounds were tentatively
      identified from the extract of Fructus aurantii (F. aurantii) based on this
      "fingerprint". Experimental outcomes indicated that the application of 2D
      separation method can reduce the matrix suppression of analytes caused by the
      coelution with interferential components and the column overloading of
      interferential components. 42 versus 23 target compounds were detected through 2D
      versus 1D method, which confirm the superiority of 2D coupled to MS in
      elimination of matrix effects.

PMID- 19091509
TI  - The epidemiology of anxiety disorders in the Arab world: a review.
AB  - Epidemiological studies are quite rare in the Arab world. The Institute for
      Development Research Advocacy and Applied Care (IDRAAC) has conducted a
      systematic review of all epidemiologic research on anxiety disorders in the Arab
      world up to 2006. Specific keywords were used in the search for affective
      disorders, namely anxiety, generalized anxiety disorder, GAD, panic, separation
      anxiety disorder, SAD, overanxious disorder, OAD, phobia, fear, post-traumatic
      stress disorder, PTSD, obsessive compulsive disorder (OCD), obsessive compulsive
      symptom (OCS), obsession, compulsion, obsessive, compulsive. All results were
      screened and categorized. Epidemiological data on prevalence, gender differences,
      age of onset, comorbidity, risk factors and treatment of anxiety disorders in the
      Arab world were found in clinical and community samples. There is an evident need
      for national data on anxiety disorders in the Arab world in order to identify the
      magnitude of these diseases and their burden on the individual and community.

PMID- 19091510
TI  - Effects of dietary conjugated linoleic acid at high-fat levels on triacylglycerol
      regulation in mice.
AB  - OBJECTIVE: Our aim was to investigate the effects of dietary conjugated linoleic
      acid (CLA) at high-fat (HF) levels on parameters related to triacylglycerol (TG)
      regulation and some potential impacts on liver damage. METHODS: Growing mice were
      fed a control diet (7% corn oil), an HF diet containing 20% corn oil, or an HF
      diet containing 3% CLA (HF + CLA) for 30 d. Tissue and organ weights, plasma and
      tissue TG levels, and parameters related to their regulation were evaluated.
      Liver oxidative status was also assessed. RESULTS: Dietary CLA showed detrimental
      and beneficial effects. CLA added to the HF diet caused hepatomegaly (+32%) and
      exacerbated the hepatic TG accumulation (+168%) observed with the HF diet without
      inducing liver damage; however, it significantly reduced plasma TG concentrations
      (-37%) and normalized muscular TG content. An increase in glutathione was
      associated with total normalization of liver lipid peroxidation. In addition, HF
      + CLA caused dystrophy of epididymal fat pads, even when the HF diet had
      increased the adipose tissue mass (30%). The biochemical mechanisms involved in
      the regulation of lipid levels were related to reduced (-20%) hepatic very low
      density lipoprotein-TG secretion and decreased muscle (-35%) and adipose (-49%)
      tissue contributions to the removal of plasma TG by lipoprotein lipase enzymes.
      CONCLUSION: Examination of CLA at HF levels showed hepatomegaly and exacerbation
      of lipid accretion as a negative impact; however, some positive aspects such as
      hypotriglyceridemia and protection against oxidative stress were also induced.
      Even the fat reduction is nutritionally important for weight control; the
      biochemical mechanisms whereby CLA mediates the potential effects could produce
      undesirable metabolic alterations.

PMID- 19091511
TI  - Effect of EGb761 supplementation on the content of copper in mouse brain in an
      animal model of Parkinson's disease.
AB  - OBJECTIVE: EGb761 is a well-defined mixture of active compounds extracted from
      Ginkgo biloba leaves with neuroprotective effects in an animal model of
      Parkinson's disease induced by 1-methyl-4-phenylpyridinium (MPP(+)). Because
      copper has been implicated in Parkinson's disease, we investigated whether the
      protective effect of EGb761 in MPP(+) neurotoxicity is related to the regulation
      of copper in the brain. METHODS: C-57BL/6 mice were pretreated with EGb761 (10
      mg/kg) daily for 17 d followed by administration of MPP(+) (0.72 mg/kg); the mice
      were sacrificed 24 h later. The copper content of the striatum, midbrain,
      hippocampus, frontal cortex, and cerebellum was analyzed by graphite furnace
      atomic absorption spectrophotometry. Copper content is expressed as mug of copper
      per gram of wet tissue. RESULTS: Copper content was reduced in the corpus
      striatum (45%; P < 0.05), and increased in the midbrain (65%; P < 0.05) and
      hippocampus (116%; P < 0.001) after MPP(+) administration. EGb761 pretreatment of
      the MPP(+) group prevented changes in the copper content of the striatum,
      midbrain, and hippocampus. No significant changes were found in the copper
      content of the cerebellum and frontal cortex in all treatment groups. CONCLUSION:
      We showed that the protective effect of EGb761 against MPP(+) neurotoxicity may
      be due in part to the regulation of copper homeostasis in the brain.

PMID- 19091512
TI  - Performance of children with epilepsy on the Rey-Osterrieth complex figure test:
      is there an effect of localization or lateralization?
AB  - SUMMARY: The effects of lateralization and localization of the epileptic focus,
      drug load of antiepileptic drug treatment and seizure frequency were examined on
      the performance of children with epilepsy on the Rey-Osterrieth complex figure
      test. Two scoring systems were used, a quantitative and a qualitative system.
      Sixty-two children with cryptogenic localization-related epilepsy between 6 and
      13 years completed the test. No effects were found for lateralization of the
      epileptic focus, drug load and seizure frequency on test performance.
      Localization of the epileptic focus appeared to have a significant effect: an
      epileptic focus in the temporal lobe caused a poorer performance on the copy of
      the test.

PMID- 19091513
TI  - Prevalence of HIV and hepatitis C infection among patients with schizophrenia.

PMID- 19091514
TI  - Progranulin, a secreted tumorigenesis and dementia-related factor, regulates
      mouse hair growth.

PMID- 19091515
TI  - Comparative pharmacodynamics for intravenous antibiotics against Gram-negative
      bacteria in Europe between 2002 and 2006: a report from the OPTAMA program.
AB  - The Optimizing Pharmacodynamic Target Attainment using the MYSTIC Antibiogram
      (OPTAMA) Program has been used globally to estimate antimicrobial exposures for
      either targeted pathogens or disease states. Herein, we utilised this methodology
      to determine antimicrobial exposures of cefepime, ceftazidime, ciprofloxacin,
      imipenem, meropenem and piperacillin/tazobactam against European-derived isolates
      of Escherichia coli, Klebsiella pneumoniae, Acinetobacter baumannii and
      Pseudomonas aeruginosa obtained in 2006 and compared these with results from
      2002. All regimens, except ciprofloxacin, provided optimal pharmacodynamic
      exposures against E. coli, whereas more regional differences were noted with K.
      pneumoniae. For K. pneumoniae, the carbapenems provided the highest likelihood of
      optimal exposures. Ciprofloxacin exposures were also noted to be low for both P.
      aeruginosa and A. baumannii. Moreover, for these two organisms higher doses
      and/or prolonged infusion of the studied beta-lactams was necessary to obtain the
      desired pharmacodynamic targets. These data reveal regional differences in the
      probability of pharmacodynamic optimisation as well as the potential utility of
      employing regimens utilising higher doses and/or prolonged infusion techniques
      when directing therapy against P. aeruginosa and A. baumannii.

PMID- 19091516
TI  - The additional costs of antibiotics and re-consultations for antibiotic-resistant
      Escherichia coli urinary tract infections managed in general practice.
AB  - The emergence of antibiotic resistance is a major threat to public health. In the
      UK, most antibiotics are prescribed in general practice but the extra costs to
      general practice of resistant infections have not previously been well described.
      We compared the costs of treating patients presenting with resistant Escherichia
      coli urinary tract infections (UTIs) (resistant to ampicillin, trimethoprim or at
      least one antibiotic) with the costs of treating patients with UTIs that were
      sensitive to all six tested antibiotics (ampicillin, trimethoprim,
      amoxicillin/clavulanic acid, cefalexin, ciprofloxacin and nitrofurantoin) with
      regard to re-consultations and antibiotics prescribed. There were significantly
      higher antibiotic costs (mean extra antibiotic cost 1.19 pounds/1.75 euros), re
      consultation costs ( 2.42 pounds/3.55 euros) and total costs ( 3.62
      pounds/5.31euros) for patients whose infections were resistant to at least one
      antibiotic compared with those with sensitive infections even after accounting
      for potentially confounding factors. Although these per-patient costs may appear
      small, they do not take into account the full additional costs of resistant UTIs
      in the community and, given the high prevalence of UTIs, the overall costs to the
      health service are substantial.

PMID- 19091517
TI  - Novel biaryl oxazolidinones: in vitro and in vivo activities with
      pharmacokinetics in an animal model.
AB  - RBx 1000075 and RBx 1000276, the new investigational oxazolidinones, have an
      extended spectrum of in vitro activity against Gram-positive pathogens and showed
      minimum inhibitory concentrations (MICs) lower than comparator drugs. MIC for 90%
      of the organisms (MIC(90)) values of RBx 1000075, RBx 1000276 and linezolid
      against the isolates tested were, respectively: methicillin-sensitive
      Staphylococcus aureus, 0.25, 1 and 4 microg/mL; methicillin-resistant S. aureus
      (MRSA), 0.5, 2 and 4 microg/mL; methicillin-sensitive Staphylococcus epidermidis,
      0.25, 1 and 2 microg/mL; methicillin-resistant S. epidermidis, 0.5, 1 and 2
      microg/mL; and enterococci, 0.25, 1 and 4 microg/mL. Against respiratory
      pathogens, MIC(90) values were: Streptococcus pneumoniae, 0.125, 0.5 and 2
      microg/mL; Streptococcus pyogenes, 1, 0.5 and 2 microg/mL; and Moraxella
      catarrhalis, 0.5, 2 and 4 microg/mL. In vivo efficacies of RBx 1000075 and RBx
      1000276 were evaluated in murine systemic infection against S. aureus (MRSA 562)
      and in a pulmonary infection model against S. pneumoniae ATCC 6303. In murine
      systemic infection, RBx 1000075 and RBx 1000276 showed efficacy against MRSA 562,
      exhibiting a 50% effective dose (ED(50)) of 6.25 and 9.92 mg/kg body weight for
      once-daily administration and 4.96 and 5.56 mg/kg body weight for twice-daily
      administration, respectively, whereas for linezolid the corresponding ED(50)
      values were 9.9 and 5.56 mg/kg body weight. In pulmonary infection with S.
      pneumoniae ATCC 6303, 50% survival was observed with RBx 1000075 at 50mg/kg once
      daily, whereas 60% survival was observed with RBx 1000276 at 50mg/kg thrice
      daily. The absolute oral bioavailabilities of RBx 1000075 and RBx 1000276 were
      48% and 73%, with half-lives of 13.5 and 3.2h, respectively. RBx 1000075 and RBx
      1000276 are promising investigational oxazolidinones against Gram-positive
      pathogens.

PMID- 19091518
TI  - In vitro activity of tigecycline against colistin-resistant Acinetobacter spp.
      isolates from Korea.

PMID- 19091519
TI  - Enhanced distribution of fourth-generation fluoroquinolones in prostatic tissue.
AB  - A recently published pharmacokinetic trial showed that the fluoroquinolone
      moxifloxacin administered to healthy volunteers at the single oral dose of 400mg
      accumulates in prostatic secretions (PS) up to a median concentration of 3.99
      mg/L and reaches a PS/plasma concentration ratio of 1.57, far higher than values
      shown by other fluoroquinolones such as norfloxacin (ratio 0.1) or ciprofloxacin
      (ratio 0.2). Ion trapping mechanisms were hypothesised to be among the
      determinants of this effect. However, whether ion trapping would solely account
      for the observed differences in fluoroquinolone pharmacokinetics was left to
      further research and discussion. In this hypothesis paper, we review various
      published evidence on the tissue distribution of moxifloxacin and other
      quinolones, suggesting that increased lipophilicity, binding to cellular matrices
      and fast cellular uptake/release kinetics may be mechanisms compatible with
      enhanced prostatic accumulation and secretion of fourth-generation
      fluoroquinolones.

PMID- 19091520
TI  - Wide dissemination of OXA-type carbapenemases in clinical Acinetobacter spp.
      isolates from South Korea.
AB  - Carbapenem-resistant Acinetobacter spp. are being increasingly reported
      worldwide, including in South Korea, where we examined 144 representative
      isolates collected in a nationwide hospital survey in 2005. Metallo-beta
      lactamases were detected in only 19.4% of isolates, none of which were
      Acinetobacter baumannii, whereas 74.3% of isolates (mostly A. baumannii)
      expressed bla(OXA) carbapenemase genes. Among the latter, 47 had bla(OXA-23)-like
      genes and 56 had upregulated bla(OXA-51)-like variants, including bla(OXA-66), (
      83), (-109) and (-115); bla(OXA-115) was a novel variant, detected in two
      isolates. bla(OXA-72) (bla(OXA-40)-like) was detected in only a single
      Acinetobacter baylyi isolate, whilst three Acinetobacter calcoaceticus isolates
      had both bla(VIM-2)-like and bla(OXA-58) genes. Pulsed-field gel electrophoresis
      (PFGE) suggested the spread of A. baumannii clones with OXA carbapenemases within
      and between hospitals. In conclusion, the recent increase in imipenem-resistant
      Acinetobacter spp. from South Korea is mostly due to OXA-type carbapenemases.

PMID- 19091521
TI  - Pharmacokinetics of once-daily dosing of ertapenem in critically ill patients
      with severe sepsis.
AB  - Adequate data on the pharmacokinetics of once-daily administration of ertapenem
      in critically ill patients are largely lacking. This single-centre, prospective,
      open-label study was performed on a cohort of eight critically ill patients with
      severe sepsis with normal renal function treated with 1g of ertapenem once daily.
      Samples of venous blood and urine were collected before infusion and at specific
      time points in the 24-h post-infusion period. Plasma and urine ertapenem levels
      were determined by reverse-phase high-performance liquid chromatography (HPLC)
      with ultraviolet detection. The non-protein-bound fraction was determined in the
      filtrate by HPLC using a Centrifree device. The current study showed a lower
      maximum plasma concentration (C(max)) (52.3.0mg/L vs. 253 mg/L) and area under
      the concentration-time curve from 0 h to infinity (AUC(0-infinity)) (188 mg h/L
      vs. 817 mg h/L) but higher volume of distribution at steady state (V(ss)) (26.8L
      vs. 5.7 L) compared with those observed in young healthy volunteers. For unbound
      ertapenem, geometric means of C(max) and AUC(0-infinity) were 29.5mg/L and 103.5
      mg h/L, respectively, and correlated negatively with hypoalbuminaemia. Unbound
      levels failed to exceed a minimum inhibitory concentration of 1mg/L for more than
      7.1h (30%) of the dosing interval in two patients. The highly variable and
      unpredictable intersubject pharmacokinetic parameters documented in this study
      resulted in suboptimal unbound concentrations in some patients. This raises the
      question as to whether ertapenem is an appropriate agent for initial use in
      critically ill patients with severe sepsis.

PMID- 19091522
TI  - Nationwide surveillance of antimicrobial resistance among non-fermentative Gram
      negative bacteria in Intensive Care Units in Taiwan: SMART programme data 2005.
AB  - A nationwide surveillance of the antimicrobial susceptibilities of glucose non
      fermentative Gram-negative bacteria isolates was conducted from 1 September 2005
      to 30 November 2005 in Taiwan. A total of 456 isolates were recovered from
      patients hospitalised in the Intensive Care Units (ICUs) of ten major teaching
      hospitals. Rates of resistant pathogens, such as ciprofloxacin-resistant
      Pseudomonas aeruginosa (19%) and imipenem-resistant Acinetobacter baumannii
      (25%), were higher than those reported in 2000 (8% and 22%, respectively).
      Increased rates of isolates with resistant phenotypes correlated with prolonged
      length of ICU stay (48h to <or=7 days vs. >7 days) for ceftazidime-non
      susceptible P. aeruginosa (20.0% and 29.7%, respectively), imipenem-non
      susceptible P. aeruginosa (4.0% and 13.5%, respectively) and imipenem-non
      susceptible A. baumannii (15.4% and 29.8%, respectively), but not for
      ciprofloxacin-resistant P. aeruginosa. Alarming rates of emergence of extensively
      drug-resistant (XDR) A. baumannii (15%) and XDR P. aeruginosa (1.8%) were found,
      particularly among those isolates that were not susceptible to tigecycline and
      colistin. Interhospital dissemination of some clones of XDR A. baumannii in
      different ICUs was also noted. This study illustrates the crucial nature of
      continuous nationwide surveillance of resistant pathogens and implementation of
      effective strategies for ICU infection control and antibiotic restriction.

PMID- 19091523
TI  - Experience with extended-infusion meropenem in the management of ventilator
      associated pneumonia due to multidrug-resistant Acinetobacter baumannii.

PMID- 19091524
TI  - Occurrence of chloramphenicol resistance and corresponding resistance genes in
      members of the Staphylococcus sciuri group.

PMID- 19091526
TI  - NMR analysis of ferromagnets: Fe oxides.
AB  - A short historical review is given on internal field NMR of ferromagnets,
      illustrated with recent pulsed NMR spectra of the elemental ferromagnets Fe, Co
      and Ni and the Fe-oxides magnetite, maghemite and hematite, which, with the
      exception of maghemite, have resonance frequencies first reported over 45 years
      ago. Since the magnetic hyperfine field at the nucleus is not known a priori, the
      original search frequency motivations are discussed along with the mechanisms for
      the initially much larger than expected ( approximately 10(3)) NMR signals that
      were observed. The (57)Fe spectra of the three principal Fe-oxide ferromagnets,
      magnetite (Fe(3)O(4)), maghemite (gamma-Fe(2)O(3)) and hematite (alpha
      Fe(2)O(3)), obtained here under uniform spectroscopic conditions, are then
      discussed in more detail, with a focus on the influence of particle size and
      vacancy content on the hyperfine fields.

PMID- 19091525
TI  - The BDI-II factor structure in pregnancy and postpartum: Two or three factors?
AB  - The purpose of the present study was to investigate the factor structure of the
      Beck Depression Inventory-II (BDI-II) in pregnancy and postpartum. Women were
      asked to fill in the BDI-II in their last trimester of pregnancy and at 3 months
      after delivery. A total of 331 pregnant women, with a mean age of 29.7 years
      (SD=4.6), and 354 mothers, aged 30.6 years (SD=4.6 years), answered the BDI-II.
      The first group was mainly nulliparas (65.6%) and the second group was mostly
      primiparas (57.4%). Factor analyses with principal components solution and
      varimax rotation were performed. Based on the scree test of Cattell a 2-factor
      solution and a 3-factor solution were explored. The 2-factor solution was
      identical in pregnancy and postpartum. Items loading in the Cognitive-Affective
      factor and in the Somatic-Anxiety factor were almost the same, though the
      Cognitive-Affective factor explained more of the BDI-II total variance in
      pregnancy, whereas in postpartum both factors explained similar total variances.
      The 3-factor solution of the BDI-II in pregnancy and postpartum slightly
      diverged. Besides the Cognitive-Affective and the Somatic-Anxiety factors, a
      third factor, Fatigue, was obtained in pregnancy while Guilt was the third factor
      identified in postpartum. This study reveals that the BDI-II 3-factor solution
      might be more appropriate to assess depressive symptoms in pregnancy and
      postpartum.

PMID- 19091527
TI  - Pretreatment of Candida rugosa lipase with soybean oil before immobilization on
      beta-cyclodextrin-based polymer.
AB  - In this study, Candida rugosa lipase was pretreated with soybean oil in order to
      allow fatty acids to bond to the active site before immobilization. The
      pretreated C. rugosa lipase was immobilized on beta-cyclodextrin-based polymer by
      crosslinking with hexamethylene diisocyanate (HMDI). This pretreated lipase
      exhibited steric hindrance around the active site such that during
      immobilization, covalent bonds were formed between the carrier and the lipase
      region far from the active site. The pretreated lipase was immobilized on a beta
      cyclodextrin-based polymer by crosslinking with hexamethylene diisocyanate with
      the activity of 42U/g-matrix, which is 5.7 times higher than that of the
      immobilized non-pretreated lipase. In addition, the immobilized lipase activity
      was maintained at levels exceeding 60% of its original activity after 10 reuses.

PMID- 19091528
TI  - A comparative kinetics study of isothermal drug release from poly(acrylic acid)
      and poly(acrylic-co-methacrylic acid) hydrogels.
AB  - A comparative study of the isothermal kinetics of the release of the drug (E)-4
      (4-metoxyphenyl)-4-oxo-2-butenoic acid (MEPBA) from poly(acrylic acid) (PAA) and
      poly(acrylic-co-methacrylic acid) (PAMA) hydrogel was performed. The isothermal
      kinetic curves of MEPBA release from the hydrogels in bidistilled water at
      different temperatures ranging from 20 to 42 degrees C were determined. The
      reaction rate constants of MEPBA release were determined using the initial rate,
      saturation rate and empirical equation developed by Peppas et.al. The so-called
      "model-fitting method" for determining the kinetics models of both the drug
      release and absorption of external solution into the hydrogel, was applied. It
      was found that the kinetics of the MEPBA release both from the PAA and PAMA
      hydrogels can be best described with the kinetics model of first order chemical
      reaction. The model's kinetics parameters of the investigated drug release
      process were calculated and significant differences for the values for PAA and
      PAMA hydrogels were found. The possibility to describe the kinetics of drug
      release with the model of reversible chemical reaction of first order was
      considered. It was found that kinetics of adsorption of the drug's solution can
      be described with kinetics model of first order chemical reaction for PAMA
      hydrogel, while for PAA hydrogel it can be described with the kinetics model
      which is characteristic for the "phase boundary controlled reaction". Based on
      the established dependences of the kinetic parameters (Ea and lnA) on the degree
      of the MEPBA released (alpha) as well as on the presence of a compensation effect
      a new molecular mechanism of drug delivery was established. According to that
      mechanism, drug release is considered as drug desorption from the
      xerogel/hydrogel's active desorption centers with different energies. The
      procedure for determining the distribution function of activation energies was
      developed. Different activation energy distribution function for PAA and PAMA
      hydrogels was established.

PMID- 19091529
TI  - Boundary effect on electrophoresis in a Carreau fluid: simulated biocolloids at
      an arbitrary position in a charged spherical cavity.
AB  - The electrophoresis of a charge-regulated spherical particle, which mimics
      biocolloids and particles covered by an artificial membrane, at an arbitrary
      position in a spherical cavity filled with a shear-thinning Carreau fluid is
      modeled under the conditions of low surface potential and weak applied electric
      field. We examine simultaneously the influences of the presence of a boundary,
      the nature of the fluid, and the charged conditions on the boundary and the
      particle surface on the electrophoretic behavior of the particle. The mobility of
      the particle in a shear-thinning Carreau fluid is larger than that in the
      corresponding Newtonian fluid, and the difference between the two increases with
      increasing mobility. For the present case, the particle is negatively charged,
      and due to the presence of an electroosmotic flow, the electrophoretic behavior
      of the particle for the case where the boundary is positively charged is more
      complicated than that when it is uncharged or negatively charged. The factors key
      to the mobility of the particle include the position and the relative size of the
      particle, the thickness of double layer, the nature of the fluid, the density of
      the dissociable functional groups on the particle surface and the associated
      equilibrium constant, and the pH of the bulk phase.

PMID- 19091530
TI  - Sorption of organophosphorous pesticides onto chickpea husk from aqueous
      solutions.
AB  - The sorption efficiency of chickpea husk of black gram variety (BGH), for the
      removal of organophosphorous pesticides (OPPs), i.e. triazophos (TAP) and methyl
      parathion (MP) from aqueous media has been investigated. Optimization of
      operating sorption parameters, i.e. particle size, sorbent dose, agitation time,
      pH, initial concentration of sorbates, and temperature has been studied. The
      sorption data fitted well to Freundlich, Langmuir and Dubinin-Radushkevich (D-R)
      sorption isotherms. The maximum sorption capacities of BGH for TAP and MP were
      calculated to be 3.5+/-0.45 and 10.6+/-0.83 mmol g(-1) by Freundlich, 0.0077+/
      0.021 and 0.025+/-0.0094 mmol g(-1) by Langmuir and 0.48+/-0.037 and 0.15+/-0.077
      mmol g(-1) by D-R isotherms respectively, employing 0.2g of sorbent, at pH 6, 90
      min agitation time and at 303 K. Application of first order Lagergren and Morris
      Weber equations to the kinetic data yielded correlation coefficients, close to
      unity and showed partial intra-particle diffusion. The negative values of
      thermodynamic parameters, i.e. DeltaH (kJ mol(-1)), DeltaS (J mol(-1) K(-1)) and
      DeltaG (kJ mol(-1)) indicate the exothermic and spontaneous nature of the
      sorption process. The sorbed pesticides were recovered by sonication with
      methanol, making the regeneration and reutilization of the sorbents promising.
      The investigated sorbent exhibited potential applications in water
      decontamination, treatments of industrial and agricultural waste waters and thus
      productively demonstrated viable use of agricultural waste material.

PMID- 19091531
TI  - [Drug news].

PMID- 19091532
TI  - Morphology and ontogenesis of Platyophrya bromelicola nov. spec., a new
      macrostome-forming colpodid (Protists, Ciliophora) from tank bromeliads of
      Jamaica.
AB  - Platyophrya bromelicola nov. spec. was discovered in tanks of bromeliads from
      Jamaica. Its morphology, ontogenesis, and small-subunit rDNA were studied using
      standard methods. Platyophrya bromelicola differs from its congeners mainly by
      the pyriform, unflattened body (vs. reniform and flattened); the free-swimming
      (planktonic) habit (vs. biofilm creepers); and the unique ability to form two
      distinct morphs, i.e., small, bacteriophagous microstomes and large, predaceous
      macrostomes. Microstomes and macrostomes can be distinguished not only by body
      size and feeding preferences but also by the postoral pseudomembrane composed of
      two vs. three to four dikinetids per kinety. The ability to form macrostomes is
      considered as an adaptation to the highly competitive habitat. Ontogenesis
      closely resembles that of other members of the family. Platyophrya bromelicola is
      distinct not only morphologically but also genetically (3.7% in the small-subunit
      rDNA) from P. vorax, a common, cosmopolitan moss and soil species.

PMID- 19091533
TI  - Classification tree modeling to identify severe and moderate vehicular injuries
      in young and middle-aged adults.
AB  - OBJECTIVES: Motor vehicle crashes are a leading cause of mortality and morbidity
      worldwide. Even though trauma centers provide the gold standard of care for motor
      vehicle crash patients with life- or limb-threatening injuries, many whose lives
      might be saved by trauma center care are treated instead at non-trauma center
      hospitals. Triage algorithms, designed to identify patients with life- or limb
      threatening injuries who should be transported to a trauma center, lack
      appropriate sensitivity to many of these injuries. The challenge to the trauma
      community is differentiating patients with life- or limb-threatening injuries
      from those with less severe injuries at the crash scene so that the patients can
      be transported to the most appropriate level of care. The purpose of this study
      was to use crash scene data available to emergency responders to classify adults
      with moderate and severe injuries. These classifiers might be useful to guide
      triage decision making. METHODS AND MATERIAL: Records of 74,626 adults, age 18-64
      years, from the National Automotive Sampling System Crashworthiness Data Systems
      database were analyzed using classification and regression trees (CART) analysis.
      Both CART models (moderate injury and severe injury) included 13 predictor
      variables. The response variables were the targeted injury severity score cut
      points for moderate and severe injury. Two final classification trees were
      developed: one that classified occupants based on moderate injury and the other
      on severe injury. Misclassification costs were manipulated to achieve the best
      model fit for each tree. RESULTS: The moderate injury classification tree had
      three splitters: police-estimated injury severity, restraint use, and number of
      persons injured. The severe injury classification tree had four splitters: police
      estimated injury severity, manner of collision, number of persons injured in the
      crash, and age. Sensitivity and specificity of the classification trees were
      93.70%, 77.53% (moderate) and 99.18%, 73.96% (severe), respectively. CONCLUSIONS:
      CART analysis can be used to classify injury severity using crash scene
      information that is available to emergency responders. This procedure offers an
      opportunity to examine alternative methods of identifying injury severity that
      might assist emergency responders to differentiate more accurately persons who
      should receive trauma center care from those who can be treated safely at a non
      trauma center hospital.

PMID- 19091534
TI  - Triglyceride/HDL-cholesterol ratio is an independent predictor for coronary heart
      disease in a population of Iranian men.
AB  - BACKGROUND AND AIMS: To determine whether triglyceride/high-density lipoprotein
      cholesterol ratio (TG/HDL-C), which has been shown to be an indicator of the
      metabolic syndrome (MetS) and insulin resistance, can predict coronary heart
      disease (CHD) independently of total cholesterol (TC) and other risk factors in
      an Iranian population with a high prevalence of MetS and low HDL-C. METHODS AND
      RESULTS: Between February 1999 and August 2001, 1824 men > or =40 years old, free
      of clinical cardiovascular diseases at baseline, were followed. Baseline
      measurements included serum level of TC, HDL-C, TG and risk factors for CHD
      including age, systolic and diastolic blood pressure, body mass index, waist
      circumference, diabetes, smoking and a family history of premature cardiovascular
      diseases. During a median follow up of 6.5 years until March 2007 (11,316 person
      years at risk), a total of 163 new CHD events (27 fatal and 136 nonfatal)
      occurred. The prevalence of MetS in subjects with TG/HDL-C > or =6.9 (top
      quartile) reached 63.6% versus 3.0% in those with TG/HDL-C <2.8 (low quartile).
      According to a stepwise Cox proportional hazard model, including TG and TG/HDL-C
      quartiles, with TC and other risk factors, men in the top quartile of TG/HDL-C
      relative to the first quartile had a significant hazard ratio (HR) of 1.75 (95%
      CI, 1.02-3.00), while TG did not remain in the model. CONCLUSION: The evaluation
      of TG/HDL-C ratio should be considered for CHD risk prediction in our male
      population with a high prevalence of MetS.

PMID- 19091535
TI  - A polymorphism in the cyclooxygenase 1 gene is associated with decreased
      inflammatory prostaglandin F2alpha formation and lower risk of cardiovascular
      disease.
AB  - This study investigates the impact of genetic variation in the cyclooxygenase-1
      (COX-1) gene on formation of the vasoconstrictive, pro-inflammatory prostaglandin
      F(2)(alpha) (PGF(2)(alpha)) and development of cardiovascular disease (CVD). We
      determined COX-1 genotypes, PGF(2)(alpha) formation and CVD prevalence in a
      Swedish cohort of 809 men at age 77 years. Of these, 237 had a history of CVD
      according to the registry data. Four of nine COX-1 single nucleotide
      polymorphisms were associated with altered formation of PGF(2)(alpha) (P<0.05).
      Two COX-1 gene variants (rs10306135 and rs883484) remained significantly
      associated with altered PGF(2)(alpha) formation after adjusted significance level
      for multiple testing (alpha-level=0.0059). Furthermore, individuals homozygote
      for the variant allele rs10306135 had lower prevalence of CVD, compared to the
      common allele (0% versus 30%, P=0.0047). In conclusion, subjects homozygote for
      the variant allele of a COX-1 gene polymorphism represent a subpopulation of men
      with decreased PGF(2)(alpha) formation and lower prevalence of CVD.

PMID- 19091536
TI  - Improving mucociliary clearance in chronic obstructive pulmonary disease.
AB  - Patients with COPD usually experience mucus hypersecretion as a result of airway
      inflammation and response to noxious stimuli. These in turn lead to worsening
      airway resistance, impaired airflow, increased work of breathing, dyspnoea and
      exercise intolerance. Mucus hypersecretion may also lead to increased
      exacerbations and poor health related quality of life (HRQL). Institution based
      pulmonary rehabilitation programs incorporating airway clearance techniques have
      been shown to improve HRQL, reduce dyspnoea and improve exercise tolerance but
      are often difficult to provide due to restricted accessibility and resource
      implications. This review examines the current evidence base and best clinical
      practice in the area of airway clearance. Mechanical devices such as the flutter
      valves, positive end expiratory pressure and high frequency chest wall
      oscillation (HFCWO) may be able to provide the benefits of improved airway
      clearance in the patient's home potentially with reduced demands on healthcare
      resources.

PMID- 19091537
TI  - Electrical stimulation and peripheral muscle function in COPD: a systematic
      review.
AB  - BACKGROUND: Chronic obstructive pulmonary disease (COPD) can lead to peripheral
      muscle atrophy and weakness. Electrical stimulation (ES) is commonly used to
      improve muscle function and structure. The purpose of this systematic review is
      to determine the effect of ES on muscle function, muscle size, fibre
      characteristics and exercise performance in patients with COPD. METHODS: A search
      was performed in seven electronic databases (Cochrane Controlled Trials Register,
      Pubmed, CINAHL, Embase, SPORTDiscus, Web of Science, PEDro). Inclusion criteria
      were: (1) randomized controlled trials (RCTs), (2) on COPD patients, (3)
      investigating a defined protocol of ES applied to the lower extremities, (4)
      analysing at least one main outcome, (5) full text available. Two reviewers
      extracted the data and evaluated the methodological quality of the studies using
      the PEDro scale. RESULTS: The initial search yielded 167 abstracts, of which five
      RCTs met the inclusion criteria. The mean (SD) methodological quality of the
      studies was 6.2+1.3 out of 10. Meta-analyses of three studies showed significant
      increases in muscle torque and walk distance in the ES groups compared to values
      in the control, sham or other treatment groups. Measures of muscle size revealed
      equivocal evidence. Patients with less severe COPD tended to show less
      improvement. CONCLUSIONS: The modest effect sizes after ES, small n, and small
      number of studies provide weak evidence for the effectiveness of ES to improve
      lower limb muscle function in COPD patients. Further study should elucidate the
      optimal parameters for ES protocols and selection criteria for responders and non
      responders.

PMID- 19091538
TI  - Prediction of household and commercial BMW generation according to socio-economic
      and other factors for the Dublin region.
AB  - Both planning and design of integrated municipal solid waste management systems
      require accurate prediction of waste generation. This research predicted the
      quantity and distribution of biodegradable municipal waste (BMW) generation
      within a diverse 'landscape' of residential areas, as well as from a variety of
      commercial establishments (restaurants, hotels, hospitals, etc.) in the Dublin
      (Ireland) region. Socio-economic variables, housing types, and the sizes and main
      activities of commercial establishments were hypothesized as the key determinants
      contributing to the spatial variability of BMW generation. A geographical
      information system (GIS) 'model' of BMW generation was created using ArcMap, a
      component of ArcGIS 9. Statistical data including socio-economic status and
      household size were mapped on an electoral district basis. Historical research
      and data from scientific literature were used to assign BMW generation rates to
      residential and commercial establishments. These predictions were combined to
      give overall BMW estimates for the region, which can aid waste planning and
      policy decisions. This technique will also aid the design of future waste
      management strategies, leading to policy and practice alterations as a function
      of demographic changes and development. The household prediction technique gave a
      more accurate overall estimate of household waste generation than did the social
      class technique. Both techniques produced estimates that differed from the
      reported local authority data; however, given that local authority reported
      figures for the region are below the national average, with some of the waste
      generated from apartment complexes being reported as commercial waste,
      predictions arising from this research are believed to be closer to actual waste
      generation than a comparison to reported data would suggest. By changing the
      input data, this estimation tool can be adapted for use in other locations.
      Although focusing on waste in the Dublin region, this method of waste prediction
      can have significant potential benefits if a universal method can be found to
      apply it effectively.

PMID- 19091539
TI  - Determination of total chlorine and bromine in solid wastes by sintering and
      inductively coupled plasma-sector field mass spectrometry.
AB  - A sample preparation method based on sintering, followed by analysis by
      inductively coupled plasma-sector field mass spectrometry (ICP-SFMS) for the
      simultaneous determination of chloride and bromide in diverse and mixed solid
      wastes, has been evaluated. Samples and reference materials of known composition
      were mixed with a sintering agent containing Na(2)CO(3) and ZnO and placed in an
      oven at 560 degrees C for 1h. After cooling, the residues were leached with water
      prior to a cation-exchange assisted clean-up. Alternatively, a simple microwave
      assisted digestion using only nitric acid was applied for comparison. Thereafter
      the samples were prepared for quantitative analysis by ICP-SFMS. The sintering
      method was evaluated by analysis of certified reference materials (CRMs) and by
      comparison with US EPA Method 5050 and ion chromatography with good agreement.
      Median RSDs for the sintering method were determined to 10% for both chlorine and
      bromine, and median recovery to 96% and 97%, respectively. Limits of detection
      (LODs) were 200mg/kg for chlorine and 20mg/kg for bromine. It was concluded that
      the sintering method is suitable for chlorine and bromine determination in
      several matrices like sewage sludge, plastics, and edible waste, as well as for
      waste mixtures. The sintering method was also applied for determination of other
      elements present in anionic forms, such as sulfur, arsenic, selenium and iodine.

PMID- 19091540
TI  - Healthcare waste management in Algeria and Mostaganem department.
AB  - Algeria as other developing countries faces an array of challenges for healthcare
      waste management. The management of healthcare waste is of major importance due
      to its public health risks and potential environmental hazards. Many efforts have
      been made by the government authorities in order to better manage the waste from
      healthcare facilities. However most healthcare facilities do not comply with the
      principles stated in Algerian legislation. A data study was made on 95 hospitals
      across the country, and the three health sectors of Mostaganem department
      (Mostaganem, Ain Tedles, and Sidi Ali) were surveyed. The yearly production of
      infectious healthcare waste in this Algerian department is estimated at 92 tons,
      which is 1.38% of the national waste production. This represents an average of
      0.15 kg/bed/day, which is lower than the national value of 0.72 kg/bed/day. The
      total healthcare waste by sector ranges from 0.7 to 1.22 kg/bed/day, and
      healthcare waste comprises 16% of total waste, which is equal to the national
      percentage.

PMID- 19091541
TI  - Regional optimization model for locating supplemental recycling depots.
AB  - In Taiwan, vendors and businesses that sell products belonging to six classes of
      recyclable materials are required to provide recycling containers at their local
      retail stores. The integration of these private sector facilities with the
      recycling depots established by local authorities has the potential to
      significantly improve residential access to the recycling process. An
      optimization model is accordingly developed in this work to assist local
      authorities with the identification of regions that require additional recycling
      depots for better access and integration with private facilities. Spatial
      accessibility, population loading and integration efficiency indicators are
      applied to evaluate whether or not a geographic region is in need of new
      recycling depots. The program developed here uses a novel algorithm to obtain the
      optimal solution by a complete enumeration of all cells making up the study area.
      A case study of a region in Central Taiwan is presented to demonstrate the use of
      the proposed model and the three indicators. The case study identifies regions
      without recycling points, prioritizes them based on population density, and
      considers the option of establishing recycling centers that are able to collect
      multiple classes of recycling materials. The model is able to generate
      information suitable for the consideration of decision-makers charged with
      prioritizing the installation of new recycling facilities.

PMID- 19091542
TI  - Electrochemical detection of protein tyrosine kinase-catalysed phosphorylation
      using gold nanoparticles.
AB  - Protein tyrosine kinase (PTK)-catalysed phosphorylation reactions of peptides are
      monitored electrochemically in the presence of Au nanoparticles (NPs) on peptide
      modified indium tin-oxide (ITO) electrodes. The method is based on the
      thiophosphorylation using adenosine 5'-[gamma-thio] triphosphate (ATP-S) as the
      co-substrate. Upon thiophosphorylation of the peptides, the Au NPs accumulate on
      the surface and can be detected electrochemically by monitoring Cl(-) oxidation
      at the Au NP surface. The activity of a clinically important PTK, Abl-T315I,
      which is implicated in the therapy of chronic myelogenous leukaemia (CML), is
      determined. Abl-T315I was assayed in combination with its highly specific
      substrate peptide EGIYDVP. The detection limit for the electrochemical detection
      of Abl-T315I activity was 10ng/mL. The performance of the biosensor was optimized
      and control experiment using non-specific peptide-modified electrodes were
      carried out. The electrochemical current response obtained from the Cl(-)
      oxidation chemistry enabled monitoring the inhibition of the thiophosphorylation
      reactions using staurosporine, a small molecule inhibitor.

PMID- 19091543
TI  - Overweight, obesity and risk of haematological malignancies: a cohort study of
      Swedish and Finnish twins.
AB  - BACKGROUND: Obesity is related to an increased risk of several forms of cancer.
      However, findings from studies on haematological malignancies are inconsistent.
      METHODS: We used prospectively collected data from two Swedish twin cohorts and
      the Finnish Twin Cohort (in total 70,067 persons) to study the effects of
      overweight and obesity on the development of leukaemia, non-Hodgkin lymphoma,
      Hodgkin's lymphoma and myeloma. The cohorts were followed from baseline through
      2002 (Sweden) and through 2004 (Finland). RESULTS: We found a risk increase of
      myeloma with a relative risk (RR) of 2.1 (95% confidence interval [CI] 1.1-3.7)
      among obese persons, a RR of 2.5 (1.0-6.2) for chronic myeloid leukaemia and a RR
      of 2.7 (0.8-9.6) for acute lymphoblastic leukaemia among overweight persons as
      compared to normal-weighted ones. CONCLUSIONS: Our results add further evidence
      suggesting that overweight and obesity may have an impact on some haematological
      malignancies, in particular myeloma.

PMID- 19091544
TI  - Effect of the chronic combined administration of cisplatin and paclitaxel in a
      rat model of peripheral neurotoxicity.
AB  - We have characterised for the first time the general and neurological side
      effects experienced when using a series of chronic non-lethal cisplatin +
      paclitaxel schedules in Wistar rats, selected according to our previous
      experience and the animals' maximum tolerated dose. At the pathological level,
      the use of combination schedules was definitely more toxic at the kidney and
      sternal bone marrow level than the single-agent schedules. At the
      neurophysiological examination based on the assessment of the nerve conduction
      velocity measurement in the tail nerve, we identified only one combination
      schedule that was more neurotoxic than the similar schedules based on single
      agent administration. This observation was confirmed by the neuropathological
      examination performed on the sciatic nerve, dorsal root ganglia, ventral and
      dorsal roots. Our study supports the hypothesis that the general and, to a lesser
      extent, neurological effects of a combination of cisplatin and paclitaxel are
      different from those of the administration of both drugs as single agents. We
      believe that these models may be useful for testing neuroprotective strategies.

PMID- 19091545
TI  - Data quality at the Cancer Registry of Norway: an overview of comparability,
      completeness, validity and timeliness.
AB  - AIM: To provide a comprehensive evaluation of the quality of the data collected
      on both solid and non-solid tumours at the Cancer Registry of Norway (CRN).
      METHODS: Established quantitative and semi-quantitative methods were used to
      assess comparability, completeness, accuracy and timeliness of data for the
      period 1953-2005, with special attention to the registration period 2001-2005.
      RESULTS: The CRN coding and classification system by and large follows
      international standards, with some further subdivisions of morphology groupings
      performed in-house. The overall completeness was estimated at 98.8% for the
      registration period 2001-2005. There remains a variable degree of under-reporting
      particularly for haematological malignancies (C90-95) and tumours of the central
      nervous system (C70-72). For the same period, 93.8% of the cases were
      morphologically verified (site-specific range: 60.0-99.8%). The under-reporting
      in 2005 due to timely publication is estimated at 2.2% overall, based on the
      number of cases received at the registry during the following year. CONCLUSION:
      This review suggests the routines in place at the CRN yields comparable data that
      can be considered reasonably accurate, close-to-complete and timely, thereby
      justifying our policy of the reporting of annual incidence one year after the
      year of diagnosis.

PMID- 19091546
TI  - Phase 0 clinical trials: recommendations from the Task Force on Methodology for
      the Development of Innovative Cancer Therapies.
AB  - The Methodology for the Development of Innovative Cancer Therapies (MDICT) task
      force has been established as an expert forum to develop practical guidance on
      the development of innovative anticancer agents, in particular targeted agents.
      The task force recently addressed the utility, design and application of Phase 0
      clinical trials in anticancer drug development. It was concluded that the role of
      non-therapeutic Phase 0 trials is controversial for several reasons, including
      the lack of clinical benefit for participating patients. However, it was
      recognised that Phase 0 trials provide an opportunity to generate essential human
      pharmacokinetic and pharmacodynamic data earlier in the drug development process,
      which could be a major advantage in the design and decision making concerning
      further clinical development of an agent. Construction of a 'decision chart' was
      highly recommended to assist investigators and sponsors in determining whether an
      agent is suitable for evaluation in a Phase 0 trial.

PMID- 19091547
TI  - Validation of novel imaging methodologies for use as cancer clinical trial end
      points.
AB  - The success or failure of a clinical trial, of any phase, depends critically on
      the choice of an appropriate primary end-point. In the setting of phases II and
      III cancer clinical trials, imaging end-points have historically, and continue
      presently to play a major role in determining therapeutic efficacy. The primary
      goal of this paper is to discuss the validation of imaging-based markers as end
      points for phase II clinical trials of cancer therapy. Specifically, we outline
      the issues that must be considered, and the criteria that would need to be
      satisfied, for an imaging end-point to supplement or potentially replace RECIST-
      defined tumour status as a phase II clinical trial end-point. The key criteria
      proposed to judge the utility of a new end-point primarily relate to its ability
      to accurately and reproducibly predict the eventual phase III end-point for
      treatment effect, which is usually assessed by a difference between two arms on
      progression free or overall survival, both at the patient and more importantly at
      the trial level. As will be demonstrated, the level of evidence required to
      formally and fully validate a new imaging marker as an appropriate end-point for
      phase II trials is substantial. In many cases, this level of evidence will only
      become available by conducting a series of coordinated prospectively designed
      multicentre clinical trials culminating in a formal meta-analysis. We also
      include a discussion of situations where flexibility may be required, relative to
      the ideal rigorous evaluation, to accommodate inevitable real-world feasibility
      constraints.

PMID- 19091548
TI  - A phase I and pharmacokinetic study of daily oral cediranib, an inhibitor of
      vascular endothelial growth factor tyrosine kinases, in combination with
      cisplatin and gemcitabine in patients with advanced non-small cell lung cancer: a
      study of the National Cancer Institute of Canada Clinical Trials Group.
AB  - INTRODUCTION: Cediranib, a potent vascular endothelial growth factor inhibitor,
      demonstrated broad pre-clinical anti-tumour activity. This study evaluated
      escalating cediranib doses with combination chemotherapy in advanced non-small
      cell lung cancer patients. METHODS: Patients received cisplatin 80 mg/m(2) on day
      1 and gemcitabine 1250 mg/m(2) on days 1 and 8 of a 3-week cycle, and daily oral
      cediranib at either 30 mg or 45 mg. Pharmacokinetics of all drugs were analysed,
      and response was assessed by RECIST. RESULTS: Fifteen patients were enrolled. No
      dose-limiting toxicities were observed during cycle 1. Fatigue, nausea,
      diarrhoea, anorexia and granulocytopaenia were common; hypertension was
      manageable. No grade 3/4 bleeding occurred. At 45 mg/d, fatigue, diarrhoea and
      thrombocytopaenia were increased; and headache, hoarseness and grade 2 hand-foot
      syndrome were observed. Cediranib had no effect on cisplatin elimination, but
      clearance of gemcitabine is significantly reduced in the presence of cediranib
      (p>0.02). Central review confirmed responses in four of 15 enrolled patients
      (26.7%, 95% CI 7.8-55%) and four of 12 evaluable patients (33.3%, 95% CI 9.9
      65%). CONCLUSION: Cediranib at 30 mg daily can be combined with standard doses of
      cisplatin/gemcitabine with encouraging anti-tumour activity, and is the
      recommended phase III dose. Toxicity is increased, but is predictable and
      manageable.

PMID- 19091550
TI  - Evaluation of lymph nodes with RECIST 1.1.
AB  - Lymph nodes are common sites of metastatic disease in many solid tumours. Unlike
      most metastases, lymph nodes are normal anatomic structures and as such, normal
      lymph nodes will have a measurable size. Additionally, the imaging literature
      recommends that lymph nodes be measured in the short axis, since the short axis
      measurement is a more reproducible measurement and predictive of malignancy.
      Therefore, the RECIST committee recommends that lymph nodes be measured in their
      short axis and proposes measurement values and rules for categorising lymph nodes
      as normal or pathologic; either target or non-target lesions. Data for the RECIST
      warehouse are presented to demonstrate the potential change in response
      assessment following these rules. These standardised lymph node guidelines are
      designed to be easy to implement, focus target lesion measurements on lesions
      that are likely to be metastatic and prevent false progressions due to minimal
      change in size.

PMID- 19091551
TI  - Production of biodiesel from bioethanol and Brassica carinata oil: oxidation
      stability study.
AB  - In the present work the synthesis from bioethanol and Brassica carinata, as
      alternative vegetable oil, using KOH as catalyst, has been developed and
      optimized by application of the factorial design and response surface methodology
      (RSM). Temperature and catalyst concentration were found to have significant
      influence on conversion. A second-order model was obtained to predict conversions
      as a function of temperature and catalyst concentration. The maximum yield of
      ester (98.04%) was obtained working with an initial concentration of catalyst
      (1.5%) and an operation temperature of (35 degrees C). Results show that the acid
      value, peroxide value, and viscosity, increased while the iodine value decreased
      with increasing storage time of the biodiesel sample. Fatty acid ethyl esters
      (biodiesel) from B. carinata oil were very stable because they did not
      demonstrate rapid increase in peroxide value, acid value, and viscosity with
      increasing storage time to a period of 12 months.

PMID- 19091552
TI  - Guava seed as an adsorbent and as a precursor of carbon for the adsorption of
      acid dyes.
AB  - The guava seed (SEGUVE) was characterized by ultimate and proximate analysis. In
      SEGUVE the principal thermal effect occurred at 363 degrees C and this can be
      attributed to the cellulose degradation, which was the main component (
      approximately 61%). The guava seed has an acidic character with a high content of
      bulk functional groups (CO) and these characteristics were affected by
      carbonization. Two samples of carbon were prepared from the seeds at 600 and 1000
      degrees C without chemical activation. Adsorption of eight acid dyes belonging to
      the monoazo and anthraquinone class was studied at 25 degrees C. The non
      carbonized SEGUVE adsorbed the acid dyes more efficiently than SEGUVE-C600 and
      SEGUVE-C1000 although the specific surface of the raw material SEGUVE was low.

PMID- 19091553
TI  - Use of Geotrichum candidum for olive mill wastewater treatment in submerged and
      static culture.
AB  - The production of lignin peroxidase (LiP), manganese peroxidase (MnP) and lipases
      by Geotrichum candidum were performed in order to control the decolourisation and
      biodegradation of olive mill wastewater (OMW). Optimisation of different factors
      showed that dilution, carbon and ammonium concentrations significantly affected
      decolourisation and activities of ligniolytic peroxidases (LiP and MnP) on OMW.
      Moreover, addition of olive oil and agitation improved the lipase production.
      Batch and continuous OMW treatments in settler or bubble column bioreactors
      showed high COD and colour removal efficiencies of 60% and 50%, respectively.
      Lipolytic activity was greater in the batch bubble column whereas, LiP and MnP
      productions were improved in the settler. The performance of the continuous
      processes decreased with the decrease of hydraulic retention time (HRT). It has
      been shown that decolourisation and biodegradation decreased with an average of
      40% and 45%, respectively, by decreasing the HRT from 4d to 1.7d.

PMID- 19091549
TI  - Long-term survival expectations of cancer patients in Europe in 2000-2002.
AB  - Period analysis has been shown to provide more up-to-date estimates of long-term
      cancer survival rates than traditional cohort-based analysis. Here, we provide
      detailed period estimates of 5- and 10-year relative survival by cancer site,
      country, sex and age for calendar years 2000-2002. In addition, pan-European
      estimates of 1-, 5- and 10-year relative survival are provided. Overall, survival
      estimates were mostly higher than previously available cohort estimates. For most
      cancer sites, survival in countries from Northern Europe, Central Europe and
      Southern Europe was substantially higher than in the United Kingdom and Ireland
      and in countries from Eastern Europe. Furthermore, relative survival was also
      better in female than in male patients and decreased with age for most cancer
      sites.

PMID- 19091554
TI  - Thiol metabolism play significant role during cadmium detoxification by
      Ceratophyllum demersum L.
AB  - In the present study, the level of thiols and activity of related enzymes were
      investigated in coontail (Ceratophyllum demersum L.) plants to analyze their role
      in combating the stress caused upon exposure to cadmium (Cd; 0-10 microM) for a
      duration up to 7d. Plants showed the maximum accumulation of 1293 microg Cd g(
      1)dw after 7d at 10 microM. Significant increases in the level of total non
      protein thiols (NP-SH) including phytochelatins (PCs) as well as upstream
      metabolites of the PC biosynthetic pathway, cysteine and glutathione (GSH) were
      observed. In addition, significant increases in the activities of cysteine
      synthase (CS), glutathione-S-transferase (GST), glutathione reductase (GR), as
      well as in vitro activation of phytochelatin synthase (PCS), were noticed in
      response to Cd. In conclusion, under Cd stress, plants adapted to a new metabolic
      equilibrium of thiols through coordinated synthesis and consumption to combat Cd
      toxicity and to accumulate it.

PMID- 19091555
TI  - Combustion characteristics and NO formation for biomass blends in a 35-ton-per
      hour travelling grate utility boiler.
AB  - Measurements were taken for a 35-ton-per-hour biomass-fired travelling grate
      boiler. Local mean concentrations of O(2), CO, SO(2) and NO gas species and gas
      temperatures were determined in the region above the grate. For a 28-ton-per-hour
      load, the mass ratios of biomass fly ash and boiler slag were 42% and 58%, the
      boiler efficiency was 81.56%, and the concentrations of NO(x) and SO(2) at 6%
      O(2) were 257 and 84 mg/m(3). For an 18-ton-per-hour load, the fuel burning zone
      was nearer to the inlet than it was for the 28-ton-per-hour load, and the
      contents of CO and NO in the fuel burning zone above the grate were lower.

PMID- 19091556
TI  - 1,3,4-Oxadiazoline derivatives as novel potential inhibitors targeting chitin
      biosynthesis: design, synthesis and biological evaluation.
AB  - Two series of 1,3,4-oxadiazoline heterocycle derivatives were designed,
      synthesized and identified. Bioactivity assays showed that all synthesized
      compounds inhibited chitin synthesis in yeast, suggesting they might be a novel
      class of potential inhibitors against chitin biosynthesis. The structure-activity
      relationships (SAR) of these compounds are discussed.

PMID- 19091557
TI  - A novel sesquiterpene quinone from Hainan sponge Dysidea villosa.
AB  - A new sesquiterpene quinone, 21-dehydroxybolinaquinone (5), together with two
      known related analogues, bolinaquinone (6) and dysidine (7), had been isolated
      from the Hainan sponge Dysidea villosa. The structure of the new compound 5 was
      elucidated on the basis of detailed analysis of spectroscopic data and by
      comparison with related model compounds. Compounds 5-7 were evaluated for the
      inhibitory activity against hPTP1B, a potential drug target for treatment of type
      II diabetes and obesity, and cytotoxic activity against Hela cell line. The
      results showed that dysidine (7) had the strongest hPTP1B inhibitory activity
      with an IC(50) value of 6.70microM and 6 had significant cytotoxic activity
      against Hela cell line with an IC(50) value of 5.45microM. New compound 5 showed
      moderate PTP1B inhibitory activity and cytotoxicity with IC(50) values of 39.50
      and 19.45microM, respectively.

PMID- 19091558
TI  - Synthesis and structure-activity relationships of 2-phenyl-1-[(pyridinyl- and
      piperidinylmethyl)amino]-3-(1H-1,2,4-triazol-1-yl)propan-2-ols as antifungal
      agents.
AB  - Continuous efforts on the synthesis and structure-activity relationships (SARs)
      studies of modified 1-benzylamino-2-phenyl-3-(1H-1,2,4-triazol-1-yl)propan-2-ols
      as antifungal agents, allowed identification of new 1-[(pyridinyl- and
      piperidinylmethyl)amino] derivatives with MIC(80) values ranging from 1410.0 to
      23.0ngmL(-1) on Candidaalbicans. These results confirmed both the importance of
      pi-pi stacking and hydrogen bonding interactions in the active site of CYP51-C.
      albicans.

PMID- 19091560
TI  - Discovery of novel thieno[2,3-d]pyrimidin-4-yl hydrazone-based inhibitors of
      Cyclin D1-CDK4: synthesis, biological evaluation, and structure-activity
      relationships.
AB  - The synthesis and evaluation of new analogues of thieno[2,3-d]pyrimidin-4-yl
      hydrazones are described. 2-Pyrdinecarboxaldehyde [6-(tert-butyl)thieno[2,3
      d]pyrimidine-4-yl]hydrazone derivatives have been identified as cyclin-dependent
      kinase 4 (CDK4) inhibitors. The potency, selectivity profile, and structure
      activity relationship of this series of compounds are discussed.

PMID- 19091559
TI  - Identification and structure-activity relationships of ortho-biphenyl
      carboxamides as potent Smoothened antagonists inhibiting the Hedgehog signaling
      pathway.
AB  - Ortho-biphenyl carboxamides, originally prepared as inhibitors of microsomal
      triglyceride transfer protein (MTP) have been identified as novel inhibitors of
      the Hedgehog signaling pathway. Structure-activity relationship studies for this
      class of compounds reduced MTP inhibitory activity and led to low nanomolar
      Hedgehog inhibitors. Binding assays revealed that the compounds act as
      antagonists of Smoothened and show cross-reactivity for both the human and mouse
      receptor.

PMID- 19091561
TI  - CoMFA and CoMSIA 3D-QSAR studies on S(6)-(4-nitrobenzyl)mercaptopurine riboside
      (NBMPR) analogs as inhibitors of human equilibrative nucleoside transporter 1
      (hENT1).
AB  - 3D-QSAR (CoMFA and CoMSIA) studies were performed on human equlibrative
      nucleoside transporter (hENT1) inhibitors displaying K(i) values ranging from
      10,000 to 0.7nM. Both CoMFA and CoMSIA analysis gave reliable models with q2
      values >0.50 and r2 values >0.92. The models have been validated for their
      stability and robustness using group validation and bootstrapping techniques and
      for their predictive abilities using an external test set of nine compounds. The
      high predictive r2 values of the test set (0.72 for CoMFA model and 0.74 for
      CoMSIA model) reveals that the models can prove to be a useful tool for activity
      prediction of newly designed nucleoside transporter inhibitors. The CoMFA and
      CoMSIA contour maps identify features important for exhibiting good binding
      affinities at the transporter, and can thus serve as a useful guide for the
      design of potential equilibrative nucleoside transporter inhibitors.

PMID- 19091562
TI  - Synthesis and evaluation of 2-pyridyl pyrimidines with in vitro antiplasmodial
      and antileishmanial activity.
AB  - A series of 2-pyridyl pyrimidines, reported inhibitors of Plasmodium falciparum
      methionine aminopeptidase 1b were synthesized and evaluated for their
      antiplasmodial activities. An analysis of physicochemical properties demonstrated
      a link between lipophilicity and antiparasitic activity. Cross screening of the
      library against cultured Leishmania donovani parasites revealed this class of
      compounds as potent inhibitors of parasite development in vitro.

PMID- 19091563
TI  - Potential utility of histamine H3 receptor antagonist pharmacophore in
      antipsychotics.
AB  - Histamine H3 receptor (H3R) antagonists have some antipsychotic properties
      although the clear molecular mechanism is still unknown. As actually the most
      effective and less side effective antipsychotics are drugs with multiple targets
      we have designed typical and atypical neuroleptics with an additional histamine
      H3 pharmacophore. The 4-(3-piperidinopropoxy)phenyl pharmacophore moiety has been
      linked to amitriptyline, maprotiline, chlorpromazine, chlorprothixene,
      fluphenazine, and clozapine. Amide, amine and ester elements have been used
      generally to maintain or slightly shift affinity at dopamine D(2)-like receptors
      (D2 and D3), to decrease affinity at histamine H(1) receptors, and to obtain H3R
      ligands with low nanomolar or subnanomolar affinity. Change of effects at D(1)
      like receptors (D1) and (D5) were heterogeneous. With these newly profiled
      compounds different antipsychotic properties might be achieved.

PMID- 19091564
TI  - Redefining the structure-activity relationships of 2,6-methano-3-benzazocines.
      Part 7: syntheses and opioid receptor properties of cyclic variants of
      cyclazocine.
AB  - A series of 7,8- and 8,9-fused triazole and imidazole analogues of cyclazocine
      have been made and characterized in opioid receptor binding and [(35)S]GTPgammaS
      assays. Target compounds were designed to explore the SAR surrounding our lead
      molecule for this study, namely the 8,9-fused pyrrolo analogue 2 of cyclazocine.
      Compared to 2, many of the new compounds in this study displayed very high
      affinity for opioid receptors.

PMID- 19091565
TI  - CB2 selective sulfamoyl benzamides: optimization of the amide functionality.
AB  - Previous research within our laboratories identified sulfamoyl benzamides as
      novel cannabinoid receptor ligands. Optimization of the amide linkage led to the
      reverse amide 40. The compound exhibited robust antiallodynic activity in a
      rodent pain model when administered intraperitoneally. Efficacy after oral
      administration was observed only when ABT, a cytochrome P450 suicide inhibitor,
      was coadministered.

PMID- 19091566
TI  - Aryloxy cyclohexyl imidazoles: a novel class of antileishmanial agents.
AB  - Thirteen novel aryloxy cyclohexane-based mono and bis imidazoles were synthesized
      and evaluated in vitro as antileishmanials against Leishmania donovani and
      cytotoxicity assessed. These compounds were better than the existing drugs,
      sodium stibogluconate and pentamidine in respect to IC(50) and SI values.
      Promising compounds were tested further in vivo. Among all, the bis
      methylimidazole with 2-fluoro, 4-nitro aryloxy group (9) exhibited significant in
      vivo inhibition of 77.9%, thus providing new structural lead for
      antileishmanials.

PMID- 19091568
TI  - Primary pontomedullary germinoma in a 12 year old boy.
AB  - Primary intracranial germinomas are rare tumors, accounting for approximately 1
      4% of all intracranial tumors. Intracranial germinomas are more commonly found in
      the suprasellar and pineal midline structures of the brain. Brainstem and
      posterior fossa germinomas are rarer still, with few reported cases in the
      literature, and little discussion of their presentation, management and clinical
      outcome. A unique case of pontomedullary germinoma, diagnosed in a 12-year-old
      boy, is described. Only six previous cases of lower brainstem germinoma have been
      reported, with varying modes of presentation and a lack of definitive management
      guidelines. Of these, all occurred in either females or a patient with
      Klinefelter's syndrome. We report the first case of a lower brainstem germinoma
      in a male without known genetic abnormality. Tumor remission was achieved with
      partial surgical resection, chemotherapy and radiotherapy.

PMID- 19091567
TI  - Asymmetric divisions, aggresomes and apoptosis.
AB  - Asymmetric cell division (ACD) is a fundamental process used to generate cell
      diversity during metazoan development that occurs when a cell divides to generate
      daughter cells adopting distinct fates. Stem cell divisions, for example, are a
      type of ACD and provide a source of new cells during development and in adult
      animals. Some ACDs produce a daughter cell that dies. In many cases, the reason
      why a cell divides to generate a dying daughter remains elusive. It was shown
      recently that denatured proteins are segregated asymmetrically during cell
      division. Here, we review data that provide interesting insights into how
      apoptosis is regulated during ACD and speculate on potential connections between
      ACD-induced cell death and partitioning of denatured proteins.

PMID- 19091569
TI  - Coma and seizures due to gas emboli following extubation.

PMID- 19091570
TI  - Differentially expressed genes from the glioblastoma cell line SHG-44 treated
      with all-trans retinoic acid in vitro.
AB  - Morphology, immunocytochemistry, growth curve assay, and flow cytometry were used
      to investigate the effects of all-trans retinoic acid (RA) on cell proliferation,
      cell cycle progression and differentiation of the astrocytoma cell line SHG-44
      from glioblastoma multiforme (World Health Organization grade IV). The
      differentially expressed genes from RA-treated and normal SHG-44 were identified
      by cDNA microarray after the cell line SHG-44 was treated with 10muM RA for 3
      days. Validation of some differentially expressed genes was performed by Northern
      Blot analysis. The expression of glial fibrillary acidic protein (GFAP) was
      markedly increased in RA-treated SHG-44 cells. Other changes included a short
      shuttle shape, small nucleus, decreased karyoplasm proportion, the formation of
      increased thin cytoplasmic processes, reduced cell growth and a 15% increase in
      G0/G1 phase cell populations. In addition, 42 known genes were identified with
      altered expression in our cDNA microarray. There was stable down-regulation of
      MDM2 and UGB as well as overexpression of SOD2, CSTB, and G3BP when RA-treated
      SHG-44 was compared with normal SHG-44. RA simultaneously suppressed the
      proliferation of SHG-44 cells significantly as well as induced differentiation
      and altered gene expression.

PMID- 19091571
TI  - Locked-in syndrome from rostro-caudal herniation.
AB  - Locked-in syndrome (LIS) is often caused by ventral pontine injury involving the
      perforating pontine vessels of the basilar artery and recovery is rarely
      reported. We report a patient who developed LIS acutely after aneurysmal
      subarachnoid haemorrhage and rostro-caudal herniation from hydrocephalus. The
      patient's clinical course and diagnostic studies suggest that the likely
      mechanism of this patient's LIS is mechanical compression of the ventral pons
      anteriorly against the clivus. The patient's slow but full recovery allowed us to
      further differentiate this clinical entity from the more common LIS due to
      ischaemic mechanisms.

PMID- 19091572
TI  - Endovascular treatment resolves non-hemorrhagic brainstem dysfunction due to
      tentorial dural AV fistula.
AB  - Tentorial dural arteriovenous fistulas (tDAVF) clinically present usually with
      subarachnoid and/or intraparenchymal hemorrhage. Reported rates range from 58% to
      92% and neurological deficits occur in 79% to 92% of patients. This is due to
      venous congestion resulting from retrograde leptomeningeal venous drainage, which
      rarely, can be clinically silent. A 69-year-old woman presented with vertigo,
      double vision and gait instability. Cerebral digital subtraction angiography
      revealed a tDAVF with retrograde cerebellar venous drainage directed through the
      vein of Galen into the straight sinus. MRI showed extensive cerebellar edema due
      to venous congestion. Clinical manifestations of cerebellar and brainstem
      dysfunction resolved completely after transarterial embolization with N
      butylcyanoacrylate.

PMID- 19091573
TI  - Two patients with intracavernous haemangiopericytoma.
AB  - Haemangiopericytomas are relatively uncommon intracranial lesions making up less
      than 2.5% of all intracranial meningiomas. Their location in the cavernous sinus
      is extremely rare. We discuss two patients with haemangiopericytomas located
      entirely within the dural confines of the cavernous sinus treated in the
      Department of Neurosurgery at King Edward Memorial Hospital. Both tumours were
      radically and successfully resected using a basal temporal extradural approach.
      No post-operative adjuvant treatment was given. There was recurrence in both
      patients 3 and 10 years after surgery. Though extremely rare, haemangiopericyomas
      can occur in the cavernous sinus. Total excision is possible through a basal
      temporal extradural approach. We briefly review the literature on the subject and
      the probable treatment strategy for this rare location of haemangiopericytoma.

PMID- 19091574
TI  - Bilateral subcortical border-zone infarction following episodes of prolonged
      defecation syncope.

PMID- 19091576
TI  - Reappearance of thalamic ataxia after a second hemorrhage at the ipsilateral
      thalamus.

PMID- 19091575
TI  - Dementia and mild cognitive impairment among non-responders to a community
      survey.
AB  - We aimed to estimate the prevalence of mild cognitive impairment (MCI) among
      elderly non-responders to a community-based survey. We conducted a two-phase,
      population-based cross-sectional study of community-dwelling individuals aged 65
      years or older in Tone, located in central Japan. The first phase of the study
      consisted of physical and cognitive examinations of individuals who responded to
      the first recruitment (quick-responders), whereas the second phase included
      individuals who did not respond in the first phase (delayed-responders). We
      compared the prevalence of MCI and dementia between delayed-responders and quick
      responders. Of the 2,698 potential candidates, 1,888 (1,619 quick-responders, 225
      delayed-responders, and 44 nursing home residents) were enrolled (70.0%). The
      prevalence of MCI was 2.3-fold increased in delayed-responders compared to the
      quick-responders (OR=2.27, 95% CI: 1.37-3.77, p=0.002, aged< or =74). In order to
      develop a method for the early detection of dementia, we must pay more attention
      to delayed-or non-responders.

PMID- 19091577
TI  - Interaction between beta-amyloid protein and heparan sulfate proteoglycans from
      the cerebral capillary basement membrane in Alzheimer's disease.
AB  - Proteoglycans are important in the pathogenesis of senile dementia of Alzheimer
      type (SDAT) by participating in amyloidogenesis. Knowledge about specific
      proteoglycan subtypes in SDAT may be of therapeutic advantage. In this study, we
      examined proteoglycan constituents of SDAT brains with reference to hyaluronic
      acid, heparan sulfate (HS), dermatan sulfate and chondroitin sulfate subtypes.
      Total proteoglycans showed a 1.6-fold increase in the hippocampus and 4.3-fold
      increase in the gyrus frontalis superior compared to non-demented elderly
      subjects. The HS subtype showed a 9.3-fold increase in hippocampus and a 6.6-fold
      increase in gyrus frontalis superior. Immunohistochemical studies of senile
      plaques revealed the expression of heparan sulfate proteoglycan (HSPG) in a
      portion of the core of typical plaques. beta-amyloid expression was positive in
      senile plaques and the degenerated neuronal processes and capillary basement
      membrane, but was negative in endothelial cells. Microglial cells adjacent to
      senile plaques were positive for HLA-DR expression, and astroglial cells positive
      for glial fibrillary acidic protein were scattered around the microglial cells.
      Immunoelectron microscopic examination showed an electron-dense reaction for HSPG
      in the thickened basement membrane adjacent to the endothelial cells of capillary
      vessels, but not inside the endothelial cells. These findings suggest that a
      markedly increased HSPG in SDAT brains is most likely caused by HSPG from the
      blood capillary basement membrane and that the degenerated processes around
      senile plaques may arise from microglial or astroglial cells.

PMID- 19091578
TI  - Synthesis and evaluation of novel chloropyridazine derivatives as potent human
      rhinovirus (HRV) capsid-binding inhibitors.
AB  - Human rhinovirus (HRV) is the most important etiologic agent causing common
      colds. No effective anti-HRV agents are currently available. In this paper we
      describe the synthesis and the evaluation of novel chloropyridazine derivatives
      (compounds 5a-g) as potent human rhinovirus (HRV) capsid-binding inhibitors.
      Results showed that compound 5e and 5f exhibited effective anti-HRV activity
      against HRV-2 and HRV-14. In addition, compound 5e and 5f showed lower
      cytotoxicity than Pirodavir.

PMID- 19091579
TI  - The synthesis of ursolic acid derivatives with cytotoxic activity and the
      investigation of their preliminary mechanism of action.
AB  - Nineteen ursolic acid derivatives (15 novel compounds) modified at the C-3 and
      the C-28 positions were synthesized. The cytotoxic activity of the derivatives
      was evaluated against HeLa, BGC-823 and SKOV3 cells by MTT assay. Inducing
      apoptosis and affecting cell cycle distribution by the derivatives in HeLa cells
      were assessed by flow cytometry and DNA fragmentation. Compounds 10b and 11b were
      particularly active to inhibit HeLa cells growth through inducing apoptosis and
      arresting cell cycle progression. The typical 'sub-G1 peak' and DNA ladder
      formation were checked and cell cycle was arrested at the S phase in a dose
      dependent manner.

PMID- 19091580
TI  - Studies on anti-HIV quinolones: new insights on the C-6 position.
AB  - The 6-desfluoroquinolones which have been developed by our group represent a
      promising class of compounds for the treatment of HIV infection since they act on
      transcriptional regulation, a crucial step in the replication cycle that has not
      been clinically exploited, yet. Focussing attention on the N-1 and C-6 positions,
      a novel series of quinolones has been synthesized. New SAR insights have been
      obtained, in particular, the hydroxyl group emerged as a suitable C-6 substituent
      when coupled with the appropriate arylpiperazine at the neighboring C-7 position.

PMID- 19091581
TI  - New pyrazoline bearing 4(3H)-quinazolinone inhibitors of monoamine oxidase:
      synthesis, biological evaluation, and structural determinants of MAO-A and MAO-B
      selectivity.
AB  - A new series of pyrazoline derivatives were prepared starting from a
      quinazolinone ring and evaluated for antidepressant, anxiogenic and MAO-A and -B
      inhibitory activities by in vivo and in vitro tests, respectively. Most of the
      synthesized compounds showed high activity against both the MAO-A (compounds 4a
      4h, 4j-4n, and 5g-5l) and the MAO-B (compounds 4i and 5a-5f) isoforms. However,
      none of the novel compounds showed antidepressant activity except for 4b. The
      reason for such biological properties was investigated by computational methods
      using recently published crystallographic models of MAO-A and MAO-B. The
      differences in the intermolecular hydrophobic and H-bonding of ligands to the
      active site of each MAO isoform were correlated to their biological data.
      Compounds 4i, 4k, 5e, 5i, and 5l were chosen for their ability to reversibly
      inhibit MAO-B and MAO-A and the availability of experimental inhibition data.
      Observation of the docked positions of these ligands revealed interactions with
      many residues previously reported to have an effect on the inhibition of the
      enzyme. Among the pyrazoline derivatives, it appears that the binding
      interactions for this class of compounds are mostly hydrophobic. All have
      potential edge-to-face hydrophobic interactions with F343, as well as pi-pi
      stacking with Y398 and other hydrophobic interactions with L171. Strong
      hydrophobic and H-bonding interactions in the MAO recognition of 4i could be the
      reason why this compound shows selectivity toward the MAO-B isoform. The very
      high MAO-B selectivity for 4i can be also explained in terms of the distance
      between the FAD and the compound, which was greater in the complex of MAO-A-4i as
      compared to the corresponding MAO-B complex.

PMID- 19091582
TI  - Application of asymmetry depending empirical formulas for (p,n alpha) reaction
      cross-sections at 24.8 and 28.5 MeV incident energies.
AB  - In this study, we have investigated the asymmetry term effect for the (p,n alpha)
      reaction cross-sections and we have obtained new coefficients for the (p,n alpha)
      reactions at 24.8 and 28.5 MeV energies. We have suggested empirical formulas
      including the new coefficients found by fitting two parameters for proton induced
      reactions. The coefficients were determined by least-squares fitting method. The
      obtained cross-section formulas with new coefficients have been discussed and
      compared with the available experimental data.

PMID- 19091583
TI  - Purification, kinetic and thermodynamic characterization of soluble acid
      invertase from sugarcane (Saccharum officinarum L.).
AB  - We report for the first time kinetic and thermodynamic properties of soluble acid
      invertase (SAI) of sugarcane (Saccharum officinarum L.) salt sensitive local
      cultivar CP 77-400 (CP-77). The SAI was purified to apparent homogeneity on FPLC
      system. The crude enzyme was about 13 fold purified and recovery of SAI was 35%.
      The invertase was monomeric in nature and its native molecular mass on gel
      filtration and subunit mass on SDS-PAGE was 28 kDa. SAI was highly acidic having
      an optimum pH lower than 2. The acidic limb was missing. Proton transfer
      (donation and receiving) during catalysis was controlled by the basic limb having
      a pKa of 2.4. Carboxyl groups were involved in proton transfer during catalysis.
      The kinetic constants for sucrose hydrolysis by SAI were determined to be:
      k(m)=55 mg ml(-1), k(cat)=21s(-1), k(cat)/k(m)=0.38, while the thermodynamic
      parameters were: DeltaH*=52.6 kJ mol(-1), DeltaG*=71.2 kJ mol(-1), DeltaS*=-57 J
      mol(-1) K(-1), DeltaG*(E-S)=10.8 kJ mol(-1) and DeltaG*(E-T)=2.6 kJ mol(-1). The
      kinetics and thermodynamics of irreversible thermal denaturation at various
      temperatures 53-63 degrees C were also determined. The half -life of SAI at 53
      and 63 degrees C was 112 and 10 min, respectively. At 55 degrees C, surprisingly
      the half -life increased to twice that at 53 degrees C. DeltaG*, DeltaH* and
      DeltaS* of irreversible thermal stability of SAI at 55 degrees C were 107.7 kJ
      mol(-1), 276.04 kJ mol(-1) and 513 J mol(-1) K(-1), respectively.

PMID- 19091584
TI  - Two cell wall Kunitz trypsin inhibitors in chickpea during seed germination and
      seedling growth.
AB  - Two Kunitz trypsin inhibitors TPI-1 and TPI-2, encoded by CaTPI-1 and CaTPI-2,
      previously identified and characterized, have been detected in chickpea (Cicer
      arietinum L.) embryonic axes from seeds imbibed up to 48 h. Their gene
      transcription commenced before germination sensu stricto was completed. The
      transcript amount of CaTPI-1 remained high until 24 h after imbibition, when the
      epicotyls started to grow, while CaTPI-2 mRNA, which appeared later, reached a
      maximum at 48 h. Both the temporal and the spatial distribution of TPI-1 and TPI
      2 proteins in the embryonic axes suggest that they perform different functions.
      The early appearance of TPI-1 in imbibed seeds suggests that it plays a
      protective role, preventing the premature degradation of the proteins stored in
      the embryonic axes. Its pattern of distribution suggests that the protein is
      involved in the regulation of vascular tissue differentiation, protecting the
      cells from some proteinases involved in programmed cell death. With regard to TPI
      2, its later synthesis after imbibition, together with its tissue distribution,
      indicates that it is mainly active following germination, during elongation of
      the embryonic axes.

PMID- 19091586
TI  - The European working time directive - facts and issues.

PMID- 19091585
TI  - Exogenous treatment with salicylic acid attenuates cadmium toxicity in pea
      seedlings.
AB  - The present study investigated the possible mediatory role of salicylic acid (SA)
      in protecting plants from cadmium (Cd) toxicity. The exposure of pea plants to
      increasing Cd concentrations (0.5, 1.0, 2.0 and 5.0 microM) during early stages
      of their establishment, caused a gradual decrease in shoot and root fresh weight
      accumulation, the rate of CO2 fixation and the activity of ribulose-1,5
      bisphosphate carboxylase (RuBPC, E.C. 4.1.1.39), the effect being most expressed
      at higher Cd concentrations. In vivo the excess of Cd-induced alterations in the
      redox cycling of oxygen-evolving centers and the assimilatory capacity of the pea
      leaves as revealed by changes in thermoluminescence emission after flash
      illumination. The levels of some important parameters associated with oxidative
      stress, namely lipid peroxidation, electrolyte leakage and proline production
      were increased. Seed pretreatment with SA alleviated the negative effect of Cd on
      growth, photosynthesis, carboxylation reactions, thermoluminescence
      characteristics and chlorophyll content, and led to decrease in oxidative
      injuries caused by Cd. The data suggest that the beneficial effect of SA during
      an earlier growth period could be related to avoidance of cumulative damage upon
      exposure to cadmium thus reducing the negative consequences of oxidative stress
      caused by heavy metal toxicity. In addition, the observed high endogenous levels
      of SA after treatment with Cd suggests that SA may act directly as an antioxidant
      to scavenge the reactive oxygen species and/or indirectly modulate redox balance
      through activation of antioxidant responses. Taken together these evidences could
      explain at some extend the protective role of SA on photochemical activity of
      chloroplast membranes and photosynthetic carboxylation reactions in Cd-stressed
      pea plants.

PMID- 19091587
TI  - Migration of an inferior vena cava filter to the right ventricular outflow tract.

PMID- 19091589
TI  - Intravenous leiomyomatosis extending to both pulmonary arteries: the longest
      tumour.

PMID- 19091588
TI  - Combined videothoracoscopic and videomediastinoscopic approach improves
      radicality of minimally invasive mediastinal lymphadenectomy for early stage lung
      carcinoma.
AB  - OBJECTIVES: To assess the feasibility and radicality of a combined thoracoscopic
      and mediastinoscopic approach to mediastinal lymphadenectomy compared to
      thoracoscopy only for minimally invasive management of early stage lung
      carcinoma. METHODS: Prospective observational study of patients undergoing
      anatomical thoracoscopic lung resection for lung carcinoma in our department in
      2007. Mediastinal lymphadenectomy was performed either thoracoscopically (VATS
      group) or by a combination of video-assisted mediastinoscopic lymphadenectomy
      (VAMLA) and thoracoscopy (VAMLA+VATS group). Inclusion criteria for the study
      were: stage Ia on CT scan, no central tumor at bronchoscopy, and no
      contraindications against lobectomy or segmentectomy. RESULTS: Eighteen
      VAMLA+VATS and fourteen VATS patients were studied. For histology, pTNM stage,
      type of resection, semiquantitative assessment of the fissure and vascular
      dissection plane, conversions, blood loss, operation time, adverse events and
      drainage time, no differences between the two groups were observed. In the VATS
      group, there was a slight preponderance of women, and right-sided tumors. In the
      VAMLA+VATS group, both the number of dissected mediastinal lymph node stations
      (mean, 6.4 stations vs 3.6 stations) and the weight of the mediastinal specimen
      (median, 11.2 groups vs 5.5 groups), were significantly higher than in the VATS
      group (p<0.05). CONCLUSIONS: A combined approach by VATS and VAMLA improves
      radicality of minimally invasive mediastinal lymphadenectomy without increase in
      operation time, morbidity, and drainage time.

PMID- 19091590
TI  - Genetic syndromes and congenital heart defects: how is surgical management
      affected?
AB  - The population of neonates and children with congenital heart defects presents
      about a 30% prevalence of associated genetic syndrome or additional extracardiac
      anomalies and may show an increased risk of death or major complication at
      cardiac surgery. Since a well-defined pattern of combined cardiac and
      extracardiac anomalies may be found in relation to specific genetic defects,
      correct understanding of the genetic issues may help improving diagnosis,
      surgical approach and final outcome of these patients. Hereby we review the
      medical and surgical issues correlated to the genetic asset in patients with
      congenital heart defects and genetic syndromes, including trisomy 21, deletion
      22q11, Noonan/LEOPARD, Turner, Marfan and Williams syndromes. Recognition of
      specific surgical risk factors can lead to the preparation of specific diagnostic
      and perioperative protocols in order to reduce operative mortality and morbidity.

PMID- 19091591
TI  - Alternatives to transplantation in the surgical therapy for heart failure.
AB  - Despite considerable improvements in the medical treatment of heart failure (HF),
      the gold standard for the treatment of these patients remains heart
      transplantation. Nevertheless, in consideration of the shortage of organ donors,
      this procedure can be offered only to a small percentage of patients who could
      benefit from a new heart. A number of innovative approaches are being
      investigated in terms of improved survival and quality of life in patients
      refractory to medical therapy and excluded from cardiac transplantation lists.
      These procedures include the optimization of medical therapy, coronary artery
      bypass surgery and valve surgery in high-risk patients, ventricular restoration
      techniques, and the implantation of ventricular assist devices as destination
      therapy. Future therapies for HF could include stem cell therapy, associated with
      standard revascularization techniques or with other procedures such as
      ventricular assist devices implantation or ventricular restoration techniques,
      allowing the potential differentiation of implanted stem cells in a resting and
      unloaded heart. The modern approach to surgical treatment of HF is
      multidisciplinary, given that the number of alternative available options to
      heart transplantation requires a close collaboration between both cardiologists
      and cardiac surgeons in treating patients with end-stage HF who are not
      candidates for transplant.

PMID- 19091592
TI  - Positron Emission Tomography in oncology: present and future of PET and PET/CT.
AB  - PET is a crucial technique in molecular imaging, allowing in vivo assessment and
      localization of pathological processes, thanks to its ability to detect very
      small amounts of radioactive molecules. This is of particular interest in
      oncology where abnormal metabolism or synthesis in tumor cells but also various
      tumor characteristics can be studied using this nuclear medicine technique. FDG
      is currently the most widely used tracer, nowadays essential in the management of
      various malignancies, with large applications in diagnosis, initial assessment,
      therapy monitoring, and recurrence detection. The combination of anatomical
      information provided by PET/CT further increased its interest. Beyond its spread
      use in daily practice, future applications of PET will involve other tracers than
      FDG and develop research applications in humans as well as in small animals.

PMID- 19091593
TI  - Effect of 1,25 dihydroxyvitamin D3 on intracellular IFN-gamma and TNF-alpha
      positive T cell subsets in pulmonary tuberculosis.
AB  - We studied the immunomodulatory effect of 1,25(OH)(2)D(3) on single cell
      expression of IFN-gamma and TNF-alpha cytokines in T cell subsets of pulmonary
      tuberculosis (PTB) patients (n=22) and normal healthy subjects (n=22). Peripheral
      blood mononuclear cells (PBMCs) were cultured with live Mycobacterium
      tuberculosis (MTB) with or without 1,25(OH)(2)D(3) (10(-7)M) for 48 h. T cell
      subsets positive for IFN-gamma and TNF-alpha were enumerated by flow cytometry
      and the culture supernatants were assayed for both the cytokines using ELISA. In
      both NHS and PTB patients, a significantly reduced percentage of IFN-gamma and
      TNF-alpha expressing CD3+, CD3+CD4+ and CD3+CD8+ T cells were observed in
      cultures stimulated with live MTB and treated with 1,25(OH)(2)D(3) compared to
      cultures without 1,25(OH)(2)D(3) (NHS; CD3+ IFN-gamma+: p<0.0001; CD3+TNF-alpha+:
      p=0.0292 and PTB; CD3+ IFN-gamma+: p=0.0292; CD3+ TNF-alpha+: p=0.0028). The
      levels of IFN-gamma and TNF-alpha in the culture supernatants of 1,25(OH)(2)D(3)
      treated cultures were also found to be significantly decreased in both groups
      (NHS; IFN-gamma: p=0.0001; TNF-alpha: p<0.0001) and (PTB; IFN-gamma: p<0.0001;
      TNF-alpha: p<0.0001). A positive correlation was observed between IFN-gamma and
      TNF-alpha expressing CD3+CD8+ T cells in MTB stimulated cultures treated with or
      without 1,25(OH)(2)D(3) in NHS (p=0.0001; p=0.001, respectively) and PTB patients
      (p=0.002; p=0.005, respectively). The present study revealed the suppressive
      effect of 1,25(OH)(2)D(3) on single cell expression of IFN-gamma and TNF-alpha by
      CD3+CD4+ and CD3+CD8+ T cells in pulmonary tuberculosis. This suppressive effect
      of 1,25(OH)(2)D(3) on proinflammatory and Th1 cytokine positive cells might have
      a role in reducing inflammation at the site of infection.

PMID- 19091594
TI  - TRAF6 negatively regulates TNFalpha-induced NF-kappaB activation.
AB  - TNF receptor-associated factor 6 (TRAF6) is an essential adaptor protein for the
      Interleukin-1 (IL-1) signaling pathway; however, its role in the signaling of
      another proinflammatory cytokine, tumor necrosis factor alpha (TNFalpha, has not
      been explored. Interestingly, we observed that TNFalpha-induced expression of IL
      6, CXCL1 and granulocyte macrophage colony stimulating factor (GM-CSF) were
      significantly enhanced in TRAF6-deficient MEFs. Compared to those observed in
      wild-type MEFs, TNFalpha-induced IkappaB kinase (IKK) activation and IkappaBalpha
      degradation were enhanced in TRAF6-deficient MEFs. Also, TNFalpha-induced DNA
      binding activity and transcriptional activation of nuclear factor kappaB (NF
      kappaB) were also augmented in TRAF6-deficient MEFs. On the other hand, TRAF6
      deficiency did not affect the TNFalpha-induced activation of mitogen-activated
      protein (MAP) kinases, ERK, JNK, and p38. Moreover, the reintroduction of
      exogenous TRAF6 into TRAF6-deficient MEFs clearly suppressed TNFalpha-induced IKK
      activation, NF-kappaB activation and subsequent cytokine expression. In contrast,
      both the deletion mutant (DeltaN) and the point mutant (C70A) of TRAF6, which is
      defective in its ubiquitin ligase activity, failed to repress TNFalpha-induced
      IKK activation, NF-kappaB activation and cytokine production. Thus, these data
      suggest that TRAF6 negatively regulates TNFalpha-induced NF-kappaB activation
      through its ubiquitin ligase activity.

PMID- 19091595
TI  - Porphyromonas gingivalis culture supernatants differentially regulate interleukin
      1beta and interleukin-18 in human monocytic cells.
AB  - Porphyromonas gingivalis is a major bacterial species implicated in chornic
      periodontitis, a disease characterized by inflammatory destruction of the tooth
      supporting tissues. Its main virulence factors are lipopolysaccharide (LPS) and
      gingipains, a group of cysteine proteinases. Interleukin (IL)-18 is a potent pro
      inflammatory cytokine with structural similarities to IL-1beta. This study aimed
      to investigate if P .gingivalis regulates IL-1beta and IL-18 in monocytic cells.
      Monomac-6 cells were challenged with P. gingivalis culture supernatants.
      Quantitative real-time PCR and ELISA were used to investigate IL-1beta and IL-18
      mRNA expression and protein secretion, respectively. P. gingivalis enhanced IL
      1beta and IL-18 mRNA expression, the former being induced earlier, but
      transiently. IL-18 up-regulation was not affected by P. gingivalis heat
      inactivation or chemical inhibition of its gingipains, whereas both treatments
      resulted in 50% reduction of IL-1beta expression. Purified P. gingivalis LPS
      enhanced both IL-1beta and IL-18 expression. However, only IL-1beta, but not IL
      18, secretion was detected, and was up-regulated by P. gingivalis. In conclusion,
      although IL-1beta and IL-18 belong to the same cytokine family, their gene
      expression and secretion are differentially regulated in human monocytic cells in
      response to P. gingivalis. Therefore, cytokines of the IL-1 family may
      participate via different pathways in the complex pathogenesis of periodontitis.

PMID- 19091596
TI  - Electromyographic evaluation of upper limb muscles involved in armwrestling sport
      simulation during dynamic and static conditions.
AB  - OBJECTIVE: To evaluate the electromyographic activity of the Pectoralis Major
      (PM), Biceps Brachii (BB), Pronator Teres (PT) and Flexor Carpi Ulnaris (FCU)
      muscles involved in simulated armwrestling. METHODS: Ten trained volunteers were
      selected to perform the armwrestling movement, during dynamic tests with 40% and
      80% of maximum voluntary load (MVL) and static tests in the initial, intermediary
      and final positions. Electromyographic and force data were normalized for
      analyses. RESULTS: In dynamic tests with 40% MVL, electric activity of the PT
      muscle was greater than FCU (p<0.01) and BB (p<0.05) muscles, and with 80% MVL,
      PM and PT muscles were the most active. In static tests, electric activity
      increased from the initial to final positions for the PM muscle (p<0.05), while
      it decreased for the BB and PT muscles (p<0.001 and p<0.05, respectively). No
      significant changes were observed for force and no correlation was found with the
      simultaneous electric activity. CONCLUSIONS: It can be concluded that the PM and
      FCU muscles participate as agonists in the simulated armwrestling whereas the BB
      and PT muscles seem to perform secondary functions. Electric activity showed to
      be dependent on the load and on the position of the upper limb, but not on the
      force produced during the movement.

PMID- 19091597
TI  - Secondary motions of the shoulder during arm elevation in patients with shoulder
      tightness.
AB  - An analysis of secondary shoulder motions (humeral rotation, humeral head
      anterior/posterior translation, scapular tipping, and scapular upward/downward
      rotation) in subjects with anterior/posterior shoulder tightness provides the
      opportunity to examine the role of tightness as a means of affecting shoulder
      motions. Subjects with shoulder tightness (anterior, n=12; posterior, n=12)
      elevated their arms in the scapular plane. Three replicated movements were
      performed to the maximum motions. Kinematics data were collected by FASTRAK 3D
      electromagnetic system. To determine if a significant difference of the secondary
      motions existed between anterior/posterior shoulder tightness, two-factor mixed
      ANOVA models with the repeated factor of elevation angle (five elevation angles)
      and the independent factor of group were calculated. The relationships between
      the self-reported functional scores (Flexilevel Scale of Shoulder Function, FLEX
      SF) and abnormal shoulder kinematics were assessed. For humeral head
      anterior/posterior translation, the subjects with posterior tightness
      demonstrated anterior humeral head translation (10mm, p=0.019) compared to
      subjects with anterior tightness. The subjects with anterior tightness
      demonstrated less posterior tipping (2.2 degrees , p=0.045) compared to subjects
      with posterior tightness. The humeral anterior translation had moderate
      relationships with FLEX-SF scores (r=-0.535) in subjects with posterior
      tightness. The scapular tipping had moderate relationships with FLEX-SF scores
      (r=0.432) in subjects with anterior tightness. In conclusion, the secondary
      motions were different between subjects with anterior and posterior shoulder
      tightness. During arm elevation, less scapular posterior tipping and less
      posterior humeral head translation in subjects with anterior and posterior
      shoulder tightness, respectively, are significantly related to self-reported
      functional disability in these subjects.

PMID- 19091598
TI  - Posture-movement changes following repetitive motion-induced shoulder muscle
      fatigue.
AB  - Repetitive motion-induced fatigue not only alters local motion characteristics
      but also provokes global reorganization of movement. However, the three
      dimensional (3D) characteristics of these reorganization patterns have never been
      documented in detail. The goal of this study was to assess the effects of
      repetitive reaching-induced arm fatigue on the whole-body, 3D biomechanical task
      characteristics. Healthy subjects (N=14) stood and performed a continuous
      reaching task (RRT) between two targets placed at shoulder height to fatigue.
      Whole-body kinematic (Vicon), kinetic (AMTI force platforms) and
      electromyographic (EMG, Noraxon) characteristics were recorded. Maximal voluntary
      isometric efforts (MVIE) of the shoulder and elbow were measured pre- and post
      RRT. Post-RRT shoulder elevation MVIE was reduced by 4.9+/-8.3% and trapezius EMG
      amplitude recorded during the RRT increased by 46.9+/-49.9% from the first to
      last minute of the RRT, indicating that arm fatigue was effectively induced.
      During fatigued reaching, subjects elevated their shoulder (11.7+/-10.5 mm) and
      decreased their average shoulder abduction angle by 8.3+/-4.4 degrees. These
      changes were accompanied by a lateral shift of the body's center of mass towards
      the non-reaching arm. These findings suggest a compensatory strategy to decrease
      the load on the fatigued shoulder musculature.

PMID- 19091599
TI  - Jogging gait kinetics following fatiguing lumbar paraspinal exercise.
AB  - A relationship exists between lumbar paraspinal muscle fatigue and quadriceps
      muscle activation. The objective of this study was to determine whether hip and
      knee joint moments during jogging changed following paraspinal fatiguing
      exercise. Fifty total subjects (25 with self-reported history of low back pain)
      performed fatiguing, isometric lumbar extension exercise until a shift in EMG
      median frequency corresponding to a mild level of muscle fatigue was observed. We
      compared 3-dimensional external joint moments of the hip and knee during jogging
      before and after lumbar paraspinal fatigue using a 10-camera motion analysis
      system. Reduced external knee flexion, knee adduction, knee internal rotation and
      hip external rotation moments and increased external knee extension moments
      resulted from repetitive lumbar paraspinal fatiguing exercise. Persons with a
      self-reported history of LBP had larger knee flexion moments than controls during
      jogging. Neuromuscular changes in the lower extremity occur while resisting knee
      and hip joint moments following isolated lumbar paraspinal exercise. Persons with
      a history of LBP seem to rely more heavily on quadriceps activity while jogging.

PMID- 19091600
TI  - MR imaging-guided percutaneous cryoablation of the prostate in an animal model:
      in vivo imaging of cryoablation-induced tissue necrosis with immediate
      histopathologic correlation.
AB  - PURPOSE: To evaluate the feasibility of magnetic resonance (MR) imaging-guided
      percutaneous cryoablation of normal canine prostates and to identify MR imaging
      features that accurately predict the area of tissue damage at a microscopic
      level. MATERIALS AND METHODS: Six adult male mixed-breed dogs were anesthetized,
      intubated, and placed in a 0.5-T open MR imaging system. A receive-only
      endorectal coil was placed, and prostate location and depth were determined on T1
      weighted fast spin-echo (FSE) MR imaging. After placement of cryoprobes and
      temperature sensors, three freezing protocols were used to ablate prostate
      tissue. Ice ball formation was monitored with T1-weighted FSE imaging. Tissue
      necrosis area was assessed with contrast-enhanced weighted MR imaging and
      compared with histopathologic findings. RESULTS: A total of 12 cryolesions (mean
      size, 1.2 cm) were bilaterally created in six prostates. Ice ball formation was
      oval and signal-free on T1-weighted FSE sequences in all cases. Postprocedural
      contrast-enhanced MR imaging typically showed a nonenhancing area of low signal
      intensity centrally located within the frozen area, surrounded by a bright
      enhancing rim in all cases. On histopathologic examination, two distinct zones
      were identified within cryolesions. Centrally, a necrotic zone with complete
      cellular destruction and hemorrhage was found. Between this necrotic zone and
      normal glandular tissue, a zone of fragmented and intact glands, interstitial
      edema, and rare acute inflammatory cells was seen. Correlation between
      nonenhancement on contrast-enhanced weighted MR images and tissue necrosis on
      pathologic examination was consistent within all six dogs. CONCLUSIONS: MR
      imaging-guided cryoablation of the prostate is technically feasible. The
      nonenhancing area on postablation contrast-enhanced weighted MR imaging
      accurately predicts the area of cryoablation-induced tissue necrosis on
      pathologic analysis.

PMID- 19091601
TI  - Is a pre-change object representation weakened under correct detection of a
      change?
AB  - We investigated whether a pre-change representation is inhibited or weakened
      under correct change detection. Two arrays of six objects were rapidly presented
      for change detection in three experiments. After detection, the perceptual
      identification of degraded stimuli was tested in Experiments 1 and 2. The
      weakening of a pre-change representation was not observed under correct
      detection. The repetition priming effect was observed for a pre-change object and
      the magnitude was equivalent to the effect for a post-change object. Under change
      blindness, repetition priming for a pre-change representation was observed when
      detection did not require report of location in Experiment 1 and was not observed
      when location was required to be reported in Experiment 2. The results of
      Experiment 3 showed that a pre-change representation was recognized at a higher
      rate under correct detection than under change blindness, reflecting a stronger
      rather than a weaker pre-change representation in the former context.

PMID- 19091602
TI  - Free will as relative freedom with conscious component.
AB  - The general notion of relative freedom is introduced. It is a kind of freedom
      that is observed everywhere in nature. In biology, incomplete knowledge is
      defined for all organisms. They cope with the problem by Popper's trial-and-error
      processes. One source of their success is the relative freedom of choice from the
      basic option ranges: mutations, motions and neuron connections. After the
      conjecture is adopted that communicability can be used as a criterion of
      consciousness, free will is defined as a conscious version of relative freedom.
      The resulting notion is logically self-consistent and it describes an observable
      phenomenon that agrees with our experience.

PMID- 19091603
TI  - Social understanding through direct perception? Yes, by interacting.
AB  - This paper comments on Gallagher's recently published direct perception proposal
      about social cognition [Gallagher, S. (2008a). Direct perception in the
      intersubjective context. Consciousness and Cognition, 17(2), 535-543]. I show
      that direct perception is in danger of being appropriated by the very cognitivist
      accounts criticised by Gallagher (theory theory and simulation theory). Then I
      argue that the experiential directness of perception in social situations can be
      understood only in the context of the role of the interaction process in social
      cognition. I elaborate on the role of social interaction with a discussion of
      participatory sense-making to show that direct perception, rather than being a
      perception enriched by mainly individual capacities, can be best understood as an
      interactional phenomenon.

PMID- 19091604
TI  - A 5 year prospective study of patient-relevant outcomes after total knee
      replacement.
AB  - OBJECTIVE: To prospectively describe self-reported outcomes up to 5 years after
      total knee replacement (TKR) in Osteoarthritis (OA) and to study which patient
      relevant factors may predict outcomes for pain and physical function (PF).
      METHODS: 102 consecutive patients with knee OA, 63 women and 39 men, mean age 71
      (51-86) assigned for TKR at the Department of Orthopaedics at Lund University
      Hospital were included in the study. The self-administered questionnaires Knee
      injury and Osteoarthritis Outcome Score (KOOS) and SF-36 were mailed
      preoperatively and 6 months, 12 months and at 5 years postoperatively. RESULTS:
      Response rate at 5 years was 86%. At 6 months significant improvement was seen in
      all KOOS and SF-36 scores (P<0.001). The percentage of patients performing more
      demanding functions related to sports and recreation increased postoperatively.
      The best postoperative result was reported at the 1 year follow-up. Compared to
      the 1 year follow-up, a significant (P<or=0.01) decline was seen at 5 years in
      the KOOS subscale activity of daily living (ADL) function (82-73) and the SF-36
      subscale bodily pain (72-63), PF (61-51) and vitality (69-59). Patients who
      scored in the lowest quartile preoperatively in the KOOS subscales pain and ADL
      made the greatest improvements to 1 year (18-82, 22-80) but also declined the
      most from 12 months to 5 years (82-72, 80-66). Being 10 years older pre
      operatively predicted 5-7 points worse scores in KOOS pain and KOOS symptoms at 1
      and 5 years. When adjusted for age, sex and comorbid conditions, pre-operative SF
      36 scores did not predict postoperative KOOS pain or PF scores. CONCLUSION:
      Compared to preoperatively, a significant improvement was still seen 5 years
      postoperatively. However, the best result was reported at 1 year, indicating a
      decline from 1 to 5 years after TKR. To fully evaluate the results of TKR with
      regard to pain and PF, follow-ups longer than 2 years are needed, and items of
      more demanding PFs should be included. Older age to some extent predicted more
      postoperative pain and other symptoms, however, no predictors of postoperative PF
      were found, indicating the difficulty of determining preoperatively who will
      benefit more or less from the procedure.

PMID- 19091605
TI  - Failure of serum transforming growth factor-beta (TGF-beta1) as a biomarker of
      radiographic osteoarthritis at the knee and hip: a cross-sectional analysis in
      the Johnston County Osteoarthritis Project.
AB  - PURPOSE: To assess associations between serum transforming growth factor-beta
      (TGF-beta1) and radiographic knee and hip osteoarthritis (rOA) in African
      American (AA) and White men and women. METHODS: Baseline data from 330
      participants in the Johnston County Osteoarthritis Project were used in the
      analysis. Radiographs were scored with the Kellgren-Lawrence scale and rOA
      defined as grade> or =2. Individual radiographic features (IRFs) were rated 0-3.
      TGF-beta1 was measured using a sandwich enzyme-linked immunosorbent assay
      (ELISA). General linear models were used to estimate associations between lnTGF
      beta1 and rOA presence, laterality or severity, and IRF presence and severity,
      adjusting for age, gender, race and body mass index. Interactions by race and
      gender were considered significant at P<0.1. RESULTS: Mean lnTGF-beta1 levels
      were higher among AAs compared to Whites, and among women compared to men
      (P<0.009). Mean lnTGF-beta1 levels were higher in those with knee osteophytes
      (OST), but this association was not significant after adjustment. There were no
      other significant differences in mean lnTGF-beta1 levels by presence, laterality,
      or severity of knee or hip rOA or IRFs. No race or gender interactions were
      identified, although a borderline significant association between lnTGF-beta1 and
      knee OST was seen among AAs (P<0.06). CONCLUSIONS: Although serum TGF-beta1
      varied by race and gender and several rOA variables, there were no independent
      significant associations with presence, laterality, or severity of knee or hip
      rOA by K-L grade or IRFs, suggesting that serum TGF-beta1 is unlikely to be
      useful as a stand-alone biomarker in OA studies. A possible association between
      TGF-beta1 and OST in AAs cannot be excluded.

PMID- 19091606
TI  - Infectious proxies and childhood leukaemia: findings from the United Kingdom
      Childhood Cancer Study (UKCCS).
AB  - The United Kingdom Childhood Cancer Study (UKCCS) was specifically designed to
      investigate the potential etiological role of infections as one of its objectives
      and information on a number of markers of infectious exposure from multiple
      sources was collected (www.ukccs.org). This study found that a mother's
      recollections of past minor illness episodes in her children were unreliable,
      producing systematic case-control differences. From birth onwards children
      diagnosed with ALL between 2-5 years were found to have had more clinically
      diagnosed infectious illness episodes (not fewer) than unaffected children, with
      those with two or more neonatal infections being diagnosed with leukaemia around
      7 months earlier than those with only one or none. The findings from these
      analyses and their implications for future research are reviewed and discussed in
      this paper.

PMID- 19091607
TI  - Specimen integrity and statistics: two essential components of good veterinary
      practice.

PMID- 19091608
TI  - Trends in opioid consumption in the Nordic countries 2002-2006.
AB  - OBJECTIVE: The purpose of the study was to examine the trends in opioid
      consumption in the five Nordic countries between 2002 and 2006 and to explore
      possible explanations for changes in the quality and quantity of opioids
      consumed. METHODS: Data on opioid consumption were extracted from the databases
      of the respective national authorities. Six strong and four weak opioids were
      included in the analysis. Data were presented as DDDs/1000 inhabitants/day. In
      addition, information on the reimbursement system and opioid prescription
      regulations in respective countries was obtained. Also, the cost of analgesic
      medication in the Nordic countries was compared as equipotent doses of CR
      morphine, CR oxycodone and transdermal fentanyl. RESULTS: During the five year
      period examined the total use of opioids showed some increase in all countries
      except Sweden. In Finland and Norway the increase in the total consumption was
      mainly due to an increase in the consumption of strong opioids while in Denmark
      the rise was due to increased consumption of weak opioids. The consumption of
      morphine was stabile or decreased slightly in all countries while the use of
      transdermal fentanyl increased in Denmark, Finland and Sweden and oxycodone in
      all countries except Iceland. The consumption of dextropropoxyphene decreased in
      all countries. Reimbursement policies or prescription regulations do not seem to
      explain the kind/type of opioids consumed or changes in their consumption.
      CONCLUSIONS: Consumption of opioid analgesics in the Nordic countries showed
      changes over the five year period that cannot be explained by pharmacology,
      price, reimbursement or prescription regulations. Marketing has most likely
      significantly influenced the type and amount of opioids consumed.

PMID- 19091609
TI  - Supercycled homonuclear dipolar decoupling sequences in solid-state NMR.
AB  - We compare the performance of the windowed phase-modulated Lee-Goldburg (wPMLG)
      and the windowed decoupling using mind boggling optimisation (wDUMBO) sequences
      at various magic-angle spinning rates and nutation frequencies of the pulses.
      Additionally, we introduce a supercycled version of wDUMBO and compare its
      efficiency with that of the non-supercycled implementation of wDUMBO. The
      efficiency of the supercycled version of wPMLG, denoted wPMLG-S2, is compared
      with a new supercycled version of wPMLG that we notate as wPMLG-S3. The
      interaction between the supercycled homonuclear dipolar decoupling sequences and
      the sample rotation is analysed using symmetry-based selection rules.

PMID- 19091610
TI  - The generating functions formalism for the analysis of spin response to the
      periodic trains of RF pulses. Echo sequences with arbitrary refocusing angles and
      resonance offsets.
AB  - The generating functions (GF) formalism was applied for calculation of spin
      density matrix evolution under the influence of periodic trains of RF pulses. It
      was shown that in a general case, closed expression for the generating function
      can be found that allows in many cases to derive analytical expressions for the
      generating function of spin density matrix (magnetization, coherences). This
      approach was shown to be particularly efficient for the analysis of multi-echo
      sequences, where one has to average over various frequency isochromats. The
      explicit analytical expressions for the generating function for echo amplitudes
      in a Carr-Purcell-Meiboom-Gill (CPMG) echo sequence, a multiecho sequence with
      incremental phase of refocusing pulse, a gradient echo sequence including
      transient period were obtained for an arbitrary flip angle and an arbitrary
      resonance offset. Comparison of the theory and the spin-echo experiments was
      done, demonstrating a good agreement.

PMID- 19091611
TI  - Optimization of 1H spin density for dynamic nuclear polarization using photo
      excited triplet electron spins.
AB  - In dynamic nuclear polarization (DNP) using photo-excited triplet electron spins,
      known as Microwave-Induced Optical Nuclear Polarization (MIONP), the attainable
      (1)H polarization is determined by the ratio of the buildup rate and the spin
      lattice relaxation rate, in turn depend on the (1)H spin density. It is shown
      that the final (1)H polarization can be enhanced by diluting the (1)H spins with
      partial deuteration. The DNP experiments are demonstrated in 0.05 mol% pentacene
      doped p-terphenyl for various (1)H abundances. It is also shown that the (1)H
      spin diffusion coefficient can be determined by examining the initial buildup
      rate of (1)H polarization for various repetition rates of the DNP sequence.

PMID- 19091612
TI  - Modulation of rat pituitary growth hormone by 670 nm light.
AB  - In rat pituitary somatotrophs, cytochrome oxidase is co-packaged with growth
      hormone (GH) in some storage granules. Because this enzyme is thought to be the
      molecular photoacceptor of red-near infrared light, and because exposure of
      diverse tissue systems to 670 nm visible light affects their biological responses
      (e.g., wound healing), we tested the idea that exposure of rat pituitary cells,
      rat hemi-pituitary glands and rat pituitary homogenates to 670 nm light in vitro
      might alter GH storage and/or release. In this report we offer evidence to show
      that light treatment (670 nm, 80s, intensity 50 mW/cm(2), energy density 4
      J/cm(2)) up-regulates GH release, in part by breakdown of intracellular,
      oligomeric GH as determined by gel filtration chromatography.

PMID- 19091613
TI  - New GLB1 mutation in siblings with Morquio type B disease presenting with mental
      regression.

PMID- 19091614
TI  - Long-term inhibition of glycosphingolipid accumulation in Fabry model mice by a
      single systemic injection of AAV1 vector in the neonatal period.
AB  - Fabry disease is caused by the deficiency of lysosomal alpha-galactosidase A
      (alpha-gal A) and usually develops clinical manifestations during
      childhood/adolescence. Adult Fabry model mice have been successfully treated by
      various viral vectors. Here, in order to examine the feasibility of preventive
      gene therapy, we compared AAV vector-mediated gene transfer into neonatal and
      adult model mice. AAV serotype 1 vector (AAV1) carrying human alpha-gal A cDNA
      driven by the CAG promoter was intravenously injected into adult (12 weeks old)
      and neonatal (2 days old) Fabry model mice, and were sacrificed for detailed
      examination 25 weeks after vector injection. AAV1 vector preferentially
      transduced the liver in male adult and sustained high concentration of alpha-gal
      A was detected in the liver, heart and plasma. In contrast, AAV1-mediated gene
      expression was suppressed in similarly treated female adult mice. When the vector
      was systemically injected into neonates, moderate increase in plasma alpha-gal A
      and cardiac-specific expression of alpha-gal A were observed independently of
      mouse sex. The high levels of alpha-gal A activity in the heart appear to be due
      to the strong activity of the CAG promoter in the heart. Globotriaosylceramide
      (Gb3) accumulation was efficiently inhibited in the liver and heart by a single
      injection into both adult and neonatal animals. The biodistribution of the AAV1
      vector and levels of alpha-gal A expression are markedly different between adult
      and neonatal mice. Neonatal injection is effective to inhibit Gb3 accumulation
      and therefore, might help prevent failure of major organs during adulthood.

PMID- 19091615
TI  - Risk factors for feline immunodeficiency virus antibody test status in Cats
      Protection adoption centres (2004).
AB  - A study was carried out to determine the prevalence of feline immunodeficiency
      virus (FIV) within a population of cats entering 10 UK adoption centres run by
      Cats Protection. All cats entering the adoption centres during 2004 were tested
      for FIV using a rapid enzyme immunoassay antibody test. The overall prevalence of
      positive test results was 3.1% (95% confidence intervals (CI) 2.7-3.5%), whilst
      the prevalence at different adoption centres varied from 0.8% (95% CI 0.1-1.5%)
      to 6.7% (95% CI 4.9-8.5%). Results of the multivariable logistic regression
      analysis showed that male cats, stray/feral cats and cats in poor health were at
      a greater risk of testing positive for FIV than female cats, cats that were
      relinquished by an owner and cats that were in good/fair health, respectively. No
      evidence was found for an association between neuter status and FIV test results.
      This study may help to identify cats that are relinquished to rescue centres with
      an increased risk of FIV for routine FIV testing.

PMID- 19091616
TI  - Monocephalus dipygus parapagus: a suspected case of complete caudal duplication
      in a British Blue kitten.
AB  - Complete caudal duplication is an extremely rare type of conjoined twinning. This
      communication reports the birth and gross features of a live conjoined British
      Blue kitten born naturally to a healthy queen. The monocephalic dipygus kitten
      exhibited a normal skull and upper body, two separate pelves, four hind limbs and
      two tails. A cleft palate and bifurcation of rostral mandible were also noted.
      The absence of maternal dystocia was unusual for conjoined twinnings.

PMID- 19091617
TI  - Pin-site myiasis: an emerging infectious complication of external bone fixation?

PMID- 19091619
TI  - [Diagnostic and treatment delays do not modify the treatment outcome of patients
      with multiform glioblastoma].
AB  - PURPOSE: To assess waiting time effect in patient with multiform glioblastoma
      (GBM) treated with 3D conformal planned postoperative radiotherapy and to
      investigate the impact of chemotherapy as first adjuvant treatment. PATIENTS AND
      METHODS: We retrospectively analyzed 94 consecutive patients with histologically
      proven GBM. Surgery was considered as macroscopically complete in 33 cases (35%).
      Median irradiation dose was 60 Gy (8-63, mean 56 Gy). Dose per fractions was 1.8
      Gy (five patients), 2 Gy (76 patients) and 2.7 Gy (13 patients). Forty patients
      received adjuvant pre-radiotherapy chemotherapy as intra-operative carmustine
      (nine patients) and adjuvant five-day protocol temozolomide alone (31 patients)
      or with cisplatinum (two patients). All patients received only one chemotherapy
      cycle. RESULTS: There were 56 males and 38 females. Median age was 62.1 years old
      (7-82, mean: 59.2 year). Median follow-up was nine months (1-49). For overall
      patients, median waiting time between fist clinical sign and start of the non
      surgical treatment was 68 days ((3-274, mean: 81.9 days). For those who received
      chemotherapy as first treatment, this waiting time was 54 days (3-221, mean 68.3
      days). For overall patients, median waiting time between surgery and beginning of
      radiotherapy was 46 days (8-401, mean 59.3 days). For patients who did not
      receive chemotherapy as first adjuvant treatment this waiting time was 46 days (
      278, mean 55.4 days). Median local control was 14.5 months. Six, 12-, 18-, and 24
      month local control rates were 75.6+/-4.6%, 57.6+/-6.2%, and 36.7+/-8% and 27.6+/
      8.2%, respectively. According to multivariate analysis, we retrieved two
      independent prognostic factors of local control, macroscopically total removal of
      the tumor [RR=2.85, IC 95% (1.3-6.5), p=0.012] and irradiation dose above 60 Gy,
      [RR=3.14, IC 95% (1.5-6.6), p=0.002]. Median overall survival was 14.3 months.
      Six-, 12-, 18, and 24-month overall survival rates were 84+/-3.9%, 55.1+/-5.9%,
      34.2+/-6.3% and 30.4+/-6.7%, respectively. There was no independent prognostic
      factor. CONCLUSION: In our series neither waiting times nor adjuvant immediate
      chemotherapy were prognosticator of local control and overall survival outcome of
      patients with glioblastoma.

PMID- 19091618
TI  - [The value of radiotherapy in the treatment of aggressive and localised gastric
      lymphomas].
AB  - PURPOSE: To evaluate the treatment results of localised aggressive gastric
      lymphomas with favourable prognosis using chemotherapy and radiotherapy. PATIENTS
      AND METHODS: Between February 1993 and December 2004, nine patients with primary
      gastric high-grade lymphoma have been treated by the Lymphoma Committee of Sfax
      (Tunisia). The sex ratio was 1.5. The mean age was 44.9 years. Histological type
      was the large cell B lymphoma in 100% of the cases. Disease was stage I in eight
      cases and stage II in one case (Ann Arbor Classification). The treatment
      consisted in primary chemotherapy followed by radiotherapy of the stomach with or
      without regional nodes (40 Gy). RESULTS: After treatment, all patients had
      complete remission. With a mean follow-up of 55.7 months, one patient was lost to
      follow-up; the other patients were alive with complete remission. No major acute
      toxicities or late effects were found. Overall survival was 100% at five years.
      CONCLUSION: Chemotherapy associated with radiotherapy can be proposed to patients
      having localised and aggressive primary gastric lymphoma with favourable
      prognosis, since this treatment is well tolerated and provides satisfactory
      control of the disease.

PMID- 19091620
TI  - Optimal use of FRAX.

PMID- 19091621
TI  - Familial Mediterranean Fever: a review for clinical management.
AB  - Familial Mediterranean Fever (FMF) is a hereditary autosomal recessive,
      autoinflammatory disorder characterized by recurrent, self-limiting episodes of
      short duration (mean 24-72 h) of fever and serositis. FMF is the most frequent
      periodic febrile syndrome among the autoinflammatory syndromes (AS), a
      heterogeneous group of recently identified diseases clinically characterized by
      recurrent febrile attacks, in the absence of autoantibodies and antigen-specific
      T lymphocytes. In FMF, periodic attacks show inter- and intra-individual
      variability in terms of frequency and severity. Usually, they are triggered by
      apparently innocuous stimuli and may be preceded by a prodromal period. The
      Mediterranean FeVer gene (MEFV) responsible gene maps on chromosome 16 (16p13)
      encoding the pyrin-marenostrin protein. The precise pathologic mechanism is still
      to be definitively elucidated; however a new macromolecular complex, called
      inflammasome, seems to play a major role in the control of inflammation and it
      might be involved in the pathogenesis of FMF. The most severe long-term
      complication is type AA amyloidosis, principally affecting the kidney and the
      cause of chronic renal failure. Two types of risk factors, genetic and non
      genetic, have been identified for this complication. Currently, the only
      effective treatment of Familial Mediterranean Fever is the colchicine. New drugs
      in a few colchicine resistant patients have been tried, but additional studies on
      larger series are necessary to draw definitive conclusions.

PMID- 19091623
TI  - Comment on the editorial by M. Wybier entitled: "Transforaminal epidural
      corticosteroid injections and spinal cord infarction".

PMID- 19091624
TI  - Selective neck dissection: a review of the evidence.
AB  - The management of regional metastatic disease in patients with oral cancer is a
      topic of controversy. Comprehensive neck dissection has been the mainstay of
      treatment historically, but clinicians have sought alternatives to limit the
      morbidity of the classic radical neck dissection. This article will review
      evidence on the applicability of selective neck dissection in two settings: as
      primary treatment of the clinically positive neck and as salvage treatment of
      recurrent neck disease after radiotherapy. In the text, for each article cited we
      supply the level of evidence thereof according to the Oxford Centre for Evidence
      based medicine.

PMID- 19091625
TI  - Contribution of polymorphism in codon 72 of TP53 gene to laryngeal cancer in
      Polish patients.
AB  - The amino acid substitution Arg72Pro in the TP53 protein has an impact on the
      biochemical and biological activity of this protein, and is associated with
      several types of cancers. However, the Arg72Pro polymorphism exhibits
      inconsistent contribution as a risk factor in various cancer types. Therefore,
      using PCR-RFLPs, we investigated the distribution of Arg72Pro genotypes and
      alleles in patients with laryngeal cancer (n=123) and controls (n=300) in Poland.
      We observed that patients with the Pro/Pro and Arg/Pro TP53 genotypes displayed a
      1.755-fold increased risk of laryngeal cancer (95% CI=1.149-2.680, P=0.0099).
      However, we did not find a significant increase in laryngeal cancer risk for the
      homozygous Pro/Pro TP53 genotype OR=2.093 (95% CI=1.046-4.192, P=0.0530). This
      result suggests that the TP53Pro variant may contribute to the risk of laryngeal
      cancer development in Polish patients.

PMID- 19091626
TI  - Fluorescence enhancement of 1-napthol-5-sulfonate by forming inclusion complex
      with beta-cyclodextrin in aqueous solution.
AB  - Fluorescence enhancement of 1-naphthol-5-sulfonate (1N5S) upon inclusion in beta
      cyclodextrin is studied by spectrophotometry and spectrofluorimetery techniques.
      The spectral shifts were only observed in the emission spectra in different
      solvents and were found to be directly correlated to the solvent's hydrogen-bond
      donor strength (alpha). Spectral changes in the absorption spectra upon the
      addition of beta-cyclodextrin to 1N5S in aqueous medium were too small to allow
      for the determination of the binding constant. On the other hand; fluorescence
      measurements show that the emission of both the anionic and neutral forms of 1N5S
      increase upon the addition of beta-cyclodextrin with an increase in the quantum
      yield by about 60%. Fluorescence measurements show 1:1 inclusion of 1N5S in the
      beta-cyclodextrin cavity with an association constant of 88+/-10M(-1). (1)H NMR
      studies are used to confirm the inclusion and to provide information on the
      geometry of 1N5S inside the cavity of beta-cyclodextrin.

PMID- 19091627
TI  - Photoluminescence of 1-phenyl,3-methyl pyrazoloquinoline derivatives.
AB  - Paper presents the absorption and photoluminescence of 7-TFM, 6-F, 6-CN, 6-TBu
      and 6-COOEt derivatives of 1-phenyl-3-methyl-1H-Pyrazolo[3,4-b]quinoline (MPPQ).
      The measured spectra are compared with the results of the quantum chemical
      calculations performed by means of the semi-empirical methods (AM1 or PM3) that
      have been applied either to the equilibrium molecular conformations in vacuo
      (T=0K) or combined with the MD simulations (T=300 K). The photoluminescent
      spectra of MPPQ dyes are highly solvatochromic. The emission bands broaden and
      shift to the red with the increasing of solvent polarity, indicating thus a
      substantial dipole moment of the excited states. According to the quantum
      chemical analysis the reason for the strong solvatochromism of MPPQ dyes is
      related with intramolecular charge transfer (ICT) state. Due to the large dipole
      moment in the twisted geometry the ICT state is believed to become the lowest
      excited state in a strongly polar environment. This would explain a considerable
      solvatochromic shift in the highly polar solvents observed for all MPPQ dyes in
      the experiment. Such hypothesis is supported by the semi-empirical quantum
      chemical evaluations.

PMID- 19091628
TI  - Fluorescence properties of a uranyl(V)-carbonate species [U(V)O(2)(CO(3))(3)](5-)
      at low temperature.
AB  - Fluorescence properties of a uranyl(V)-carbonate species in solution are reported
      for the first time. The fluorescence characteristics of the stable aqueous
      uranyl(V)-carbonate complex [U(V)O(2)(CO(3))(3)](5-) was determined in a frozen
      solution (T=153K) of 0.5mM uranium and 1.5M Na(2)CO(3) at pH 11.8 by time
      resolved laser-induced fluorescence spectroscopy (TRLFS). Two different
      wavelengths of 255nm and 408nm, respectively were used to independently of each
      other excite the uranyl(V)-carbonate species. The resulting U(V) fluorescence
      emission bands were detected between 380nm and 440nm, with a maxima at 404.7nm
      (excitation with 255nm) and 413.3nm (excitation with 408nm), respectively. It was
      found that by using an excitation wavelength of 255nm the corresponding
      extinction coefficient was much higher and the fluorescence spectrum better
      structured than the ones excited at 408nm. The fluorescence lifetime of the
      uranyl(V)-carbonate species was determined at 153K as 120micros. TRLFS
      investigations at room temperature, however, showed no fluorescence signal at
      all.

PMID- 19091629
TI  - Successful treatment of severe Crimean-Congo hemorrhagic fever with supportive
      measures without ribavirin and hypothermia.

PMID- 19091630
TI  - Thrombomodulation via CLEC-2 targeting.
AB  - CLEC-2 is a C-type lectin-like molecule that has recently been identified as a
      receptor on the surface of platelets. Ligand binding by CLEC-2 promotes
      phosphorylation of a tyrosine in the cytoplasmic domain YXXL motif of CLEC-2 by
      Src kinases and further downstream signalling events trigger platelet activation
      and aggregation. The snake venom protein rhodocytin and the endogenous protein
      podoplanin have been identified as ligands. The structures of CLEC-2 and
      rhodocytin suggest that ligand binding could cluster CLEC-2 molecules at the
      platelet surface, so initiating signalling. CLEC-2 is a promising target for
      therapeutic strategies to inhibit platelet activity in thrombotic vascular
      disease.

PMID- 19091632
TI  - How has agriculture influenced the geography and genetics of animal parasites?
AB  - Have farmers inadvertently promoted the distribution, and limited the diversity,
      of animal parasites? Abundant and broadly distributed livestock hosts evidently
      harbor exceptionally uniform populations of Trichinella, Taenia, Toxoplasma and
      Sarcocystis, indicating a fruitful avenue for future research on how we have
      influenced parasite evolutionary ecology.

PMID- 19091631
TI  - Breast cancer by proxy: can the microenvironment be both the cause and
      consequence?
AB  - Breast cancer is one of the most clear-cut examples of a solid tumor in which
      systemic cues play a decisive part in its development. The breast tissue is
      constantly subjected to changes in hormone levels and modifications in the
      microenvironment. This scenario is even more striking during tumor development
      because of the dramatic loss or aberration of basement membrane (BM) and
      myoepithelial cells and the gain of peritumoral myofibroblasts. We suggest that
      the microenvironment, defined here as all components of the mammary gland other
      than luminal and/or tumor epithelial cells, might be instrumental in maintaining
      organ integrity and in promoting, and at times even initiating, breast cancer
      development. As such, the tumor microenvironment and its constituents, alone or
      in combination, might serve as promising targets for therapy.

PMID- 19091633
TI  - Management of premature ovarian failure.
AB  - Premature ovarian failure (POF), a major life-changing condition that affects a
      significant proportion of young women, remains an enigma and the researcher's
      minefield. As women increasingly survive childhood cancers due to improved
      iatrogenic interventions, the number of POF sufferers will inevitably increase.
      Numerous questions relating to this condition remain unanswered, and several
      important management issues are yet to be addressed. The challenges posed by this
      important condition range from difficulties with nomenclature to the absence of
      specific standardized diagnostic criteria and management guidelines. There is a
      particularly urgent need to determine the optimum therapeutic hormonal regimens
      in women with POF, both in terms of immediate symptom relief and also for
      protection against the long-term sequelae of an early menopause. This chapter
      discusses the management of POF, highlights the challenging issues, reviews the
      current literature and proposes a practical management outline based on the
      authors' own practice.

PMID- 19091634
TI  - Cortisol controlled release by mesoporous silica.
AB  - In this study four types of SBAs were synthesized and then impregnated with
      hydrocortisone. One is a straight SBA-15, obtained using Pluronics P123 as
      structuring agent; two others were modified using 1,3,5-trimethylbenzene as
      additive, and the fourth one was prepared using sodium iodide as additive. Three
      of these have in common a p6 mm symmetry with nanotubes packed hexagonally, yet
      they differ in their functional groups. The fourth sample is basically
      disordered. The drug release kinetics showed two stages: a fast-rate early stage
      dominated by the controlled release of the hydrocortisone adsorbed in the
      macropores of the reservoir, followed by a slow-rate delivery that we assume is
      controlled by the hydrocortisone diffusion through the nanopores. It is shown
      that the release kinetics can be strongly influenced by using different co
      additives.

PMID- 19091635
TI  - Chromatographic methods for the analyses of 2-halofatty aldehydes and
      chlorohydrin molecular species of lysophosphatidylcholine.
AB  - Plasmalogens are targeted by hypohalous acids resulting in the production of 2
      chlorofatty aldehydes, 2-bromofatty aldehydes and chlorohydrin species of
      lysophosphatidylcholine. These novel lipids may have important roles in the
      pathophysiological sequelae of cardiovascular diseases as well as serve as
      biomarkers of cardiovascular disease. Accordingly, the discovery of these new
      lipid species have required the development of techniques for their purification
      and quantification. Thin layer chromatography, high performance liquid
      chromatography (LC) and gas chromatography (GC) of these lipids and their
      derivatives have provided a battery of tools for their analyses. These lipids
      have been quantified using flame ionization detection (FID) and mass spectrometry
      (MS).

PMID- 19091636
TI  - Trends in U.S. food prices, 1950-2007.
AB  - The potential effect that food prices may have on the health of the U.S.
      population needs to be further explored, particularly in light of the rising food
      prices currently being observed. Declining food prices over time have been
      singled out as a main contributor, for example, to the rising trend in obesity.
      In this paper we use data from the Bureau of Labor Statistics, the American
      Chamber of Commerce Researchers Association, the Consumer Expenditure Survey, and
      the United States Department of Agriculture to analyze trends in various types of
      food prices, to create a food price index, and to estimate the price of a
      calorie. Results may be used by future researchers in estimating the health
      implications of these trends. We find that while the general trend in food prices
      has been declining, that of restaurant meal prices and prices of fruits and
      vegetables has risen over time. It is doubtful that the decline in food prices
      has been sufficiently large to account for the large increase in caloric intake
      that is said to have contributed to the obesity epidemic in the U.S.

PMID- 19091638
TI  - WITHDRAWN: Dual mesh-muscle pocket with/without abdominal lift for immediate
      implant-based breast reconstruction after skin-sparing mastectomy.

PMID- 19091637
TI  - Neomycin binding preserves extracellular matrix in bioprosthetic heart valves
      during in vitro cyclic fatigue and storage.
AB  - Bioprosthetic heart valve (BHV) cusps have a complex architecture consisting of
      an anisotropic arrangement of collagen, glycosaminoglycans (GAGs) and elastin.
      Glutaraldehyde (GLUT) is used as a fixative for all clinical BHV implants;
      however, it only stabilizes the collagen component of the tissue, and other
      components such as GAGs and elastin are lost from the tissue during processing,
      storage or after implantation. We have shown previously that the effectiveness of
      the chemical crosslinking can be increased by incorporating neomycin trisulfate,
      a hyaluronidase inhibitor, to prevent the enzyme-mediated GAG degradation. In the
      present study, we optimized carbodiimide-based GAG-targeted chemistry to
      incorporate neomycin into BHV cusps prior to conventional GLUT crosslinking. This
      crosslinking leads to enhanced preservation of GAGs during in vitro cyclic
      fatigue and storage. The neomycin group showed greater GAG retention after both
      10 and 50 million accelerated fatigue cycles and after 1 year of storage in GLUT
      solution. Thus, additional binding of neomycin to the cusps prior to standard
      GLUT crosslinking could enhance tissue stability and thus heart valve durability.

PMID- 19091639
TI  - Hypafix versus Mefix.

PMID- 19091640
TI  - Laparoscopic hernia repair compromising rectus abdominis muscle flap for perineal
      reconstruction despite initial patent vessels.

PMID- 19091641
TI  - Re-defining pseudoptosis from a 3D perspective after short scar-medial pedicle
      reduction mammaplasty.
AB  - BACKGROUND: Bottoming out is a well-known phenomenon described with reduction
      mammaplasty (RM). To date, the evaluation of post-operative bottoming out remains
      an imprecise science. The following study reports the application of three
      dimensional (3D) photography to objectively investigate changes in breast
      morphology. METHODS: Patients undergoing medial pedicle RM had 3D photographs
      (Konica Minolta V910) taken during the early and late post-operative period
      (early=60-120 days; late=400-500 days). 3D images were compared and bottoming out
      was assessed with 3D parameters and vectors including total breast volume,
      volumetric tissue distribution above and below the Central (C) plane, distance of
      the C-plane to the lowest point of the breast, and maximum anterior-posterior
      projection from the chest wall. RESULTS: Post-operative images from 15
      consecutive RM patients showed an average volume of 556+/-144 cm3 (early) and
      441+/-183 cm3 (late). The percent of tissue in the upper pole of the breast
      changed from the early to late post-operative period (76% vs. 69%, respectively;
      p<0.01). The distance from a fixed C-plane to the inferior pole significantly
      increased (42+/-15 mm early vs. 51+/-18 mm late; p<0.01). AP projection decreased
      by an average of 6.23 mm (p<0.01). The lateral border of the IMF significantly
      dropped by 6.27 mm. CONCLUSIONS: This study objectively describes both the
      occurrence of bottoming out and the quantitative amount in terms of changes in
      volumetric distribution, surface topography and breast projection. With 3D
      photography, plastic surgeons can perform objective evaluation of breast
      transformation over time, which ultimately will aid in planning to allow for
      better surgical outcomes.

PMID- 19091642
TI  - Osteogenesis of the construct combined BMSCs with beta-TCP in rat.
AB  - BACKGROUND: The use of artificial bone graft substitutes has increased as the
      surgical applications widen and the availability of allograft bone decreases. The
      present study was to evaluate the construct combined bone marrow stromal cells
      (BMSCs) with beta-tricalcium phosphate (beta-TCP) as bone substitute implanted in
      rat dorsal muscles. METHODS: To study the osteogenic capability in vivo,
      specimens were harvested on 1 week, 4 weeks and 8 weeks after implantation, and
      were analyzed by hematoxylin and eosin (HE) staining. The percentages of new bone
      formation for each implant type and implantation period were determined by
      histomorphometry. RESULTS: After 1 week of implantation, new bone formation for
      both beta-TCP and BMSCs+beta-TCP group had no formed. After 4 weeks of
      implantation, the amount of bone formation was increased to 1.32 % in beta-TCP
      group and 6.35% in BMSCs+beta-TCP group. After 8 weeks of implantation, more bone
      was found in the BMSCs+beta-TCP group (21.58 %), while in the beta-TCP group bone
      formation was increased to 4.78%. Significant differences between the two groups
      have been observed. CONCLUSIONS: Based on these results, we conclude that bone
      substitutes constructed by porous beta-TCP scaffold loaded with osteogenically
      induced BMSCs could promote newly formed bone.

PMID- 19091643
TI  - Stable coverage of a cervico-thoracic defect with an extended lower trapezius
      myocutaneous flap.

PMID- 19091644
TI  - Salvage of infected tissue expanders using a new continuous irrigation method
      with intermittent aspiration.
AB  - When tissue expander sites are infected, it often results in removal of the
      expander. To salvage the infected expander and achieve full expansion, we devised
      a new continuous irrigation method with intermittent aspiration. In this method,
      the continuous irrigation of the tissue expander pocket was performed without
      removal of the expander. Saline was continuously infused at 50 ml h(-1) via the
      IVH catheter and intermittent aspiration was done at 10 cm H(2)O negative
      pressure via the suction drainage tube for 3 min per hour until the infection was
      under control. We performed this method on two cases of infection of tissue
      expander sites and salvaged both expanders. After controlling the infection,
      reconstructions were successfully performed with enough skin expansion. In this
      method, the expander left in the pocket acts not only in maintaining the expanded
      pocket but also helps in irrigating the inner surface of the skin pocket. This
      method can perform effective irrigation with a relatively small amount of saline
      (1200 ml per day) and salvage the tissue expander.

PMID- 19091645
TI  - A new instrument for achieving a natural nasofrontal angle.

PMID- 19091646
TI  - Platysma-mastoid suture to prevent ear lobule deformity following facelift.

PMID- 19091647
TI  - [Quantum dots in oncological surgery: the future for surgical margin status].
AB  - Quantum dots (QDs) are semi-conductor nanocrystals that emit fluorescence on
      excitation with a light source. They have excellent optical properties, including
      high brightness and resistance to photobleaching. Their spectroscopic properties
      can be modulated by many factors. Recent progress in developing QDs enable us to
      control the size, shape and surface functionality of nanoparticles for potential
      application in cancer imaging. QDs with near-infrared emission could be applied
      to identify sentinel lymph-node. Conjugation of QDs with biomolecules could be
      used to target tumors in vivo. This article reviewed recent developments and
      issues in nanotechnology with a particular focus on applications to the surgery.

PMID- 19091648
TI  - [Margin status in ductal carcinoma in situ of the breast].
AB  - For women with ductal carcinoma in situ, no residual disease after breast
      conserving surgery is one of the most important factors associated with local
      recurrence. Surgeons can rely on the pathologic examination of the margin and
      measure of margins width to indicate complete excision. Surgeon and pathologist
      have to do well and together to make margin can be assessed. Margin status is a
      prognostic factor for predicting residual disease. Margin width > 2 mm is
      associated with very few residual diseases. Margin status is also a prognostic
      factor for local recurrence. Local recurrence after margin width > 2-3 mm
      followed by radiotherapy is nearly equivalent to local recurrence after
      mastectomy. An evaluation based on margin status and other risk factors of
      recurrence (grade, necrosis, size and age like the Van Nuys Prognostic Index) can
      help clinicians to stratify patients into low-risk, intermediate risk and high
      risk group of local recurrence. The validity of such index must be confirmed and
      margin width must be studied more precisely. Currently, breast conserving surgery
      with histological margin width > 2 mm followed by radiation therapy is necessary
      to obtain satisfactory local control. Such margin status with good aesthetic
      outcomes is not so easy to obtain with classic lumpectomy and oncologic breast
      surgery is a helpful technique.

PMID- 19091649
TI  - [Margin status in invasive breast cancer].
AB  - Breast conserving surgery and mastectomy are equivalent for overall survival.
      However, the rate of local recurrence is higher for breast conserving surgery.
      Several predictive factors for local recurrence have been identified and some of
      them such as margins of resection, radiation therapy, chemotherapy, and
      hormonotherapy can be modified. The aim of this study is to review arguments in
      the literature to define optimal margins of resection. The orientation of the
      specimen and the inking of lateral margins are essentials for the
      histopathological analysis. Lateral margins are the most important since the
      resection is close to the pectoral muscle. According to the literature, the rate
      of local recurrence is higher when margins are positive. Moreover, the presence
      of tumoral cells on specimen after a re-excision is correlated with the
      positivity of the margins. There are no agreements about the number of
      millimeters requested to consider a margin sufficient. However, two millimeters
      seem to show a decrease of local recurrence. The influence of extensive
      intraductal component on local recurrence risk has been studied. Several factors
      are correlated and to define independent factors seem to be interesting.

PMID- 19091650
TI  - [Cervical pathology: significance and therapeutic impact of margin status].
AB  - Margin status in cervical pathology is one of most important predictive factor of
      recurrent disease. Even if management of surgical biopsy is standardized, quality
      of surgical procedure is fundamental. Frozen section can be realise in order to
      complete surgical procedure if margins are involved. Extemporaneous exam of
      endocervical margin during conservative surgery and vaginal cuff during radical
      surgery is a precious information for surgeon. Endocervical status for
      conization, parametrial and vaginal margins have been reported to be a factor
      predictive of residual disease. During radical trachelectomy, margins involvment
      of one of these three topographic zone is an important predictive factor of
      recurrent disease and can be an obstacle to preserve fertility.

PMID- 19091651
TI  - [Rectal cancer margin].
AB  - Treatment of rectal cancer has dramatically improved over the last twenty years.
      During previous years surgeons and pathologists have focused mainly on distal
      longitudinal margin as the main parameter for anal conservation. New knowledge on
      the prognostic role of circumferential margin and its influence on locoregional
      recurrence rate and patients' survival has led to a more standardized surgery and
      the definition of the total mesorectal excision concept. As a consequence the
      rates of positive circumferential margins and locoregional recurrence have
      decreased in population studies as well as in prospective randomized trials.

PMID- 19091652
TI  - [Surgical margin status in hepatectomy for liver tumors].
AB  - It is admitted that only complete tumor clearance with negative surgical margins
      provides benefit for patients undergoing surgery for hepatobiliary malignancies.
      For hepatocellular carcinoma, since micrometastases disseminate via portal venous
      branches, anatomic resection is preferred over non-anatomic resection in liver
      resection carried out with curative intent. Thus, an anatomic liver resection
      with a wider resection margin theoretically gives a higher potential for cure.
      However, preserving non-tumorous liver parenchyma is an important consideration,
      especially in cirrhotic liver resection to decrease the incidence of
      postoperative liver failure. The optimal liver resection margin is still
      controversial. It seems that a resection margin of 2 cm is associated with a
      decreased postoperative recurrence rate and improved survival outcomes especially
      for hepatocellular carcinoma <or= 2 cm. Due to the unsatisfying alternatives in
      the medical and interventional treatment of intrahepatic cholangiocarcinoma,
      hepatic resection, whenever technically possible, should be enforced. Expected
      narrow hepatic resection margins should not exclude patients from potentially
      curative surgery, and should not be used as a reason to establish palliative
      treatment instead since R1 resection is compatible with long-term survival.
      Aggressive hepatic surgery could and should therefore be performed if the peri
      operative mortality is low. For hilar cholangiocarcinoma, surgical radicality has
      been shown in multivariate analyses of multiples studies to be the only parameter
      with a significant impact on survival. Extended right-side hepatectomies seems to
      give the best oncologic results. A predicted margin of < 1 cm after resection of
      hepatic colorectal metastases should not be used as an exclusion criterion for
      resection and will not impair patients' prognosis. Resection should be performed
      whatever the width of the surgical margin, rather than not performing the
      resection at all.

PMID- 19091653
TI  - [Ductal adenocarcinoma of the head of the pancreas: a critical study of R1
      resection rates].
AB  - Complete resection (R0) remains the only potentially curative treatment of ductal
      adenocarcinoma of the pancreas. Locoregional and metastatic recurrence is
      frequent. The rate of microscopic margin involvement (R1) varies markedly in the
      literature (5 to 85%) and R1 resections are frequently underreported. Despite
      appeals for standardization over a decade, there is currently a lack of quality
      assessment for pathological examination of pancreaticoduodenectomy specimens
      (PDS). What exactly constitutes the minimal clearance remains to be established.
      A standardized protocol for pathological examination should be used to assess the
      correlation between R1 resections and clinical outcome (that is not observed in
      all studies), and the effect of (neo)adjuvant treatment in clinical trials. The
      aim of an ongoing multicenter French protocol is to evaluate the R1 resections
      rate in France, with a standardized protocol for pathological examination, and
      the impact of R1 status on the clinical outcome.

PMID- 19091654
TI  - [Surgical margins in soft tissue sarcoma].
AB  - OBJECTIVES: To state about adequacy of surgery margins in soft tissue sarcoma
      (STS). METHODS: Review of the relevant literature. RESULTS: The end point for
      measuring the quality of margins in STS is local recurrence (LR). The rate of LR
      in specialised centres lies between 16 and 22%. The rates of LR should be given
      by the actuarial estimations. The methods determining margins are variable in the
      literature. By the quantitative methods, measuring the distance between the
      tumour edge and the limits of resection on the excision specimen, a twofold
      difference in LR is seen between adequate and inadequate margins. This difference
      is fourfold by the qualitative, consensual method from the French Sarcoma Group,
      appearing here more discriminatory. Obtaining adequate margins depends on the
      planned character of surgery, tumour size, tumour infiltration and grade.
      CONCLUSION: An actuarial 5-year LR rate ranging from 10 to 20% is a criterion for
      good quality of surgery. These results appear to be obtained best in specialised
      centres.

PMID- 19091655
TI  - [Everolimus (RAD001) and solid tumours: a 2008 summary].
AB  - Mammalian target of rapamycin (mTOR), a serine/threonine kinase, is a mediator in
      the downstream signalling pathway phosphatidylinositol 3-kinase/Akt, playing a
      key role in regulation of basic cellular functions including growth and cell
      proliferation. The inhibitor of mTOR RAD001, or everolimus (Novartis Pharma AG),
      is a hydroxyethyl ether rapamycin derivative administered orally. Everolimus
      showed an important anti-angiogenic and antiproliferative activity on cell lines
      derived from human tumours and on xenograft models of human tumours. This
      molecule appears well tolerated, with skin reactions, stomatitis, myelosupression
      and metabolic abnormalities transient and reversible with interruption of
      treatment. Clear data suggest antitumor activity, including tumour regression and
      prolonged stable disease, which has been reported in patients with a variety of
      malignancies, especially those with metastatic renal cell cancer. Here, we review
      the preclinical data of this compound with current clinical results and future
      developments.

PMID- 19091656
TI  - [Interest of the radiotherapy-hormonotherapy association in the treatment of the
      high-risk prostate cancer].
AB  - Treatment of high-risk prostate cancer - localized or locally advanced - is based
      on the combination of external irradiation and hormonal treatment by LHRH
      analogue (aLHRH) according to the results of phases III randomized trials RTOG
      and/or EORTC trials. These trials show a significant improvement of overall or
      specific survival. Localized prostate cancer require 6-month complete androgen
      blockade, while locally advanced prostate cancer need a long-term hormonal
      treatment for a duration ranging from 2,5 to 3 years. Some trials, which have a
      long follow-up show that the risk of cardiovascular death is not significantly
      increased by hormonal treatment.

PMID- 19091657
TI  - [Regulatory T-cells and hepatocellular carcinoma: implication of the regulatory T
      lymphocytes in the control of the immune response].
AB  - Hepatocellular carcinoma (HCC) is the fifth most common cancer worldwide and also
      the third most common cause of cancer-related death. HCC arises most frequently
      in males with cirrhosis, which is most often a consequence of chronic hepatitis
      infection (HBV and HCV) or alcohol abuse. To date, the only effective approaches
      for patients with HCC are resection or liver transplantation. Immunological
      mechanisms are important in the surveillance of malignancy and control of tumor
      progression. Tumor-infiltrating lymphocytes (TILs) have been described in HCC,
      and extensive infiltration has been associated with reduced tumor recurrence
      following resection. However continued tumor-growth, despite the presence of a
      lymphocytic infiltration, including tumor-specific T-cells within and surrounding
      tumors, suggests a failure of immune control. Although, many mechanisms have been
      proposed for this attenuated immune response, it becomes evident that direct
      suppression of effector cells, supported by regulatory T-cells could play a
      pivotal role in the suppression of immune response to tumors. Initially described
      in context of immune disorders such as inflammatory autoimmune pathologies,
      regulatory T lymphocytes are characterized by their capacity to inhibit T helper
      response. To date, several regulatory T-cells are described, however CD4+CD25+
      regulatory T-cells and Tr1 subpopulations remain best characterized. Currently,
      there is no evidence for direct implication of CD4+CD25+ regulatory T-cells in
      the malignancy and control of HCC progression. However, recent studies showed
      that both regulatory T-cells subpopulations and particularly Tr1 have been
      implicated in the modulation of the immune response during HCV chronic infection,
      supporting HCC progression.

PMID- 19091658
TI  - [How to improve patients and investigators' information on clinical trials: the
      example of French registry for clinical trials in oncology].
AB  - Cancer patients' willingness to be informed about clinical trials (CT) is rapidly
      increasing. Health professionals are also interested on being informed on CT in
      order to provide their patients the best access to innovative treatments. The
      French cancer plan (2003-2007) launched the creation of a national registry for
      clinical trials in oncology. The primary objective was to guarantee patients and
      investigators comprehensive, high quality and updated information about ongoing
      CT in France, accessed at www.e-cancer.fr. A second objective was to establish a
      single channel for registration of French CT in conformity with the requirements
      of the International Committee of Medical Journal Editors. A unique Web access
      for patients and investigators was created. Information important for patients is
      presented in the first pages. Scientific information is accessible under further
      clicks. An information page about clinical research, intended for patients and
      their relatives, was also prepared in collaboration with patients' advocacy and
      healthcare professionals. Achieving comprehensiveness is one of the founding
      principles of the RECF. Over 600 CT were registered as of end of July 2008. All
      French academic sponsors have registered their CT; the publication of the
      industrial trials has begun in early 2008.

PMID- 19091659
TI  - [Biomarkers of lipid peroxidation: analytical aspects].
AB  - During these last years, oxidative stress has been implicated in various
      pathological situations. The difficulty is to choose a convenient marker to
      appreciate its importance in vivo because of analytical problems of specificity
      and sensitivity. The oxidized lipids, formed during lipid peroxidation,
      illustrate these problems. Among these markers are 'primary' products such as
      hydroperoxides, or 'secondary' products such as malondialdehyde (MDA), 4
      hydroxynonenal (4-HNE) and isoprostanes. They are all measurable in biological
      fluids and analytical methods used are sometimes complex and require sample
      preparation involving extraction and purification steps. F2-isoprostanes are
      certainly the most specific markers of lipid peroxidation but also the most
      difficult to measure. Many assays have been recently developed. Some, such as gas
      or liquid chromatography coupled with mass spectrometry are the 'gold standard'
      methods, they allow to measure different F2-isoprostanes but require special
      apparatus. Others, like immunoassay methods measure one isoprostane, they are
      simpler to perform and accessible to a greater number of laboratories but still
      lack of specificity.

PMID- 19091660
TI  - Potential role of the "NADPH oxidases" (NOX/DUOX) family in cystic fibrosis.
AB  - Cystic fibrosis (CF), is the most common life-shortening autosomal recessive
      disorder in Caucasians. It is caused by mutations in a single gene on the long
      arm of chromosome 7 that encodes the cystic fibrosis transmembrane conductance
      regulator (CFTR) protein. CF is characterized by abnormal Na+ and Cl- ion
      transport in several tissues, including the lungs, pancreas, gastrointestinal
      tract, liver, sweat glands, and male reproductive system. Progressive pulmonary
      disease is the dominant clinical feature of CF and accounts for morbidity and
      mortality. The inflammation characterized by an overabundance of activated
      neutrophils and macrophages on the respiratory epithelial surface is associated
      to a high production of reactive oxygen species (ROS) which contribute to the
      pathogenesis of cystic fibrosis. ROS could have different origins but the role of
      the NADPH oxidase system is essential. The "NADPH oxidases" (NOX/DUOX) family is
      an enzymatic complex formed by cytosolic and membrane subunits. Until now several
      homologues of the phagocytic NADPH oxidase have been identified in different
      tissues and it has been shown that the lungs preferentially expressed DUOX1-2.
      Thus, DUOX1-2 could be implicated in the anti-infectious defense system. The role
      of DUOX enzymes as a source of ROS in cystic fibrosis is examined as they could
      contribute to a better understanding of molecular mechanisms in CF. Moreover they
      could be a potential target for a new therapeutic approach.

PMID- 19091661
TI  - Serum levels of ochratoxin A in healthy subjects and in nephropathic patients in
      Tunisia.
AB  - Ochratoxin A is a fungal toxin produced by Aspergillus and Penicillinium. These
      Fungi oftenly contaminate plant-derived products, and can generate deleterious
      toxic effects in man. In this study, ochratoxin A was determined in human serum
      samples collected in Tunisia, using high performance liquid chromatography (HPLC)
      and fluorescence detection. The samples were collected from healthy subjects (n =
      105) as well as from patients with various kidney disorders. Five different kinds
      of kidney disorders were represented: transplanted subjects (27), patients with
      Chronic Interstitial Nephropathy (22) of known etiology, Chronic Vascular
      Nephropathy (26), Chronic Glomerular Nephropathy (26) or Chronic Interstitial
      Nephropathy (30) of unknown etiology. Mean concentrations of ochratoxin A in the
      healthy group was 0.49+/-0.79 ng/mL. The highest mean concentration of ochratoxin
      A was found in group of Chronic Interstitial Nephropathy of unknown etiology
      1.25+/-1.22 ng/mL. Significant differences were also observed according to the
      geographic origin of healthy subjects and nephropthic patients within Tunisia.

PMID- 19091662
TI  - [Relationship between hyperhomocysteinemia and C677T polymorphism of methylene
      tetrahydrofolate reductase gene in a healthy Algerian population].
AB  - Plasmatic homocysteine concentration depends mostly on 5,10 methylene
      tetrahydrofolate reductase (MTHFR) polymorphisms, a key enzyme in folate
      metabolism. The most common point mutation C677T is associated to cardiovascular
      and neurological pathologies; its ethnic repartition is quite heterogenic. In the
      present study, we proposed to describe the genotypic and allelic frequencies of
      C677T polymorphism and its influence on plasmatic homocysteine level in a healthy
      Algerian population. The investigation was turned on 100 apparently healthy
      voluntary subjects. Homocysteine concentration was determined using an
      immunoassay by fluorescence polarisation on IMx. Genotypes were determined by RT
      PCR (Light cycle 480). Mean homocysteine concentration value was 14,69 +/- 7,30
      micromol/L. 41% of people sample show a moderate hyperhomocysteinemia (>15
      micromol/L). For the MTHFR C677T, estimated frequency of the allele T in the 100
      people sample was about 35,5% with genotypic frequency of 6%. Plasmatic
      homocysteine is significantly higher in people carrying allele T: (CC vs CT: 11,8
      +/- 2,97 micromol/L vs 15,47 +/- 6,74 micromol/L, p = 0,0004); (CC vs TT: 11,8 +/
      2,97 micromol/L vs 30,05 +/- 13,35 micromol/L, p = 0,01) and (CT vs TT: 15,47 +/
      6,74 micromol/L vs 30,05 +/- 13,35 micromol/L, p = 0,021). Our study shows an
      intermediate allelic frequency that joins the North-South world gradient and a
      high hyperhomocysteinemia prevalence. C677T polymorphism of MTHFR seems playing a
      predominant role in the moderate hyperhomocyteinemia. These two observations
      should be taken into consideration in the evaluation of morbid and/or lethal
      pathologies predisposition in the Algerian population.

PMID- 19091663
TI  - [Biological profile of type I allergies at Mohamed V Hospital (Rabat- Morocco)].
AB  - Allergic diseases are ranked fourth considering the world health organization
      classification of diseases. The consequences linked to these ailments are huge
      for public health economics and the diagnosis is awkward due to clinical
      polymorphism and multifactorial aetiologies. The allergologic diagnosis is the
      result of weighing in clinical and biological findings. The biological assessment
      is made of qualitative specific and multiple-allergen serum IgE test, which once
      positive drives to skin test and each allergen-specific IgE level determination
      to conclude. Our study aims at displaying biological analysis results of incoming
      patients with clinical allergy conditions. We carried out a nine months
      retrospective study, from June 2007 to March 2008, with 200 outwards patients
      involved. Blood samples were collected using dry tubes and as recommended we
      first did screening tests for respiratory (Pharmacia Phadiatop) and food (fx 5)
      allergens, then for positive samples we proceeded to serum specific IgE assay
      (UniCap, Phadia). We also realized the total IgE assay on 46 patients using Roche
      Elecsys 2010 technology. 49% of patients enrolled in the study were positive to
      aerollergens, d1 Dermatophagoides pteronyssinus being the most incriminated
      (96.4%), and 2.5% to food allergens. On 13% of patients, we noticed a double
      sensitization to d1 and g6 (pollen of grasses). Concerning the total IgE dosage,
      we found 50% of patients tested with normal values, 28% of whom having a positive
      allergologic screening test. Further studies matching clinical data, skin tests
      to serum IgE assay are necessary to draw the profile of respiratory and
      dermatological allergies for our patients.

PMID- 19091664
TI  - [Inaccuracy of glucose meters. Automatic correction for hematocrit variations and
      the presence of exogenous interfering components].
AB  - Seven hospital-based glucose monitoring systems (meters) were evaluated with
      particular attention to those analytical interferences encountered in intensive
      care patients. Imprecision differed little between meters and remained altogether
      within acceptable limits. Inaccuracy, as measured by comparison with a hexokinase
      method presented with significant differences, yet without exceeding acceptable
      limits either. All meters but one showed an important bias when hematocrit
      departed from the reference interval. Two meters would not distinguish maltose
      from glucose. Three showed an important positive bias in the presence of
      acetaminophen and four a comparable bias in the presence of ascorbate. Only one
      meter was unaffected by both such exogenous interferences and hematocrit
      variations, owing to built-in hematocrit and electrochemical blank measuring
      devices. This meter also showed narrowest correlation with hexokinase methods. At
      a time when intensive care patients are being submitted to ever tighter glycemic
      control, it is desirable and our results show that it is now possible to tighten
      accordingly the acceptability criteria of glucose meters used to this end.

PMID- 19091665
TI  - [The EMIT Tacrolimus assay: development of application protocol for Roche Hitachi
      902 analyzer].
AB  - Tacrolimus (FK506, Prograf) is a potent macrolide immunosuppressant used for
      prevention of organ transplant rejection following transplantation. It has been
      clear for many years that, as a drug with a low therapeutic index and high inter
      and intrapatients pharmacokinetic variability, it requires individualized
      monitoring of blood concentration. Several methods have been developed to monitor
      tacrolimus; immunoassays, bioassays and LCMSMS. The purpose of this study was to
      develop application for the EMIT Tacrolimus assay on the Hitachi 902 analyzer.
      Application protocol on this analyzer is nonexistent. We optimize the programm
      chemistry parameters to arrive at the following assay characteristics on the
      Hitachi 902. Assay results were linearly related to the concentration for the
      wide range which was examinated (0 - 40 ng/mL). We report the precision,
      accuracy, linearity, sensitivity of this assay. The CV was less than 10%.
      Calibration stability is at least 21 days. The reagent cartridge in the
      instrument is stable 2 months between runs. However, specimens from 87 kidney
      transplant patients were analyzed and results were compared to those from the
      Abbott MEIA II assay on IMx analyzer. Correlation between the methods was good (r
      = 0,961). This application for the EMIT 2000 Tacrolimus assay on the Hitachi 902
      analyzer enhances the versatility of the immunoassay for routine therapeutic drug
      monitoring of this immunosuppressant in the clinical setting.

PMID- 19091666
TI  - [Comparison of two ELISA tests to study the seroprevalence of herpes simplex 1 et
      2 infection in a maternity near Paris].
AB  - The diagnosis of herpes simplex virus (HSV) genital infection is primarily
      clinical. The primary indication for serodiagnosis is to detect seronegativity in
      pregnant women at risk of acquiring the HSV virus during the course of their
      pregnancy. In this study, two ELISA tests were compared for the detection of HSV
      infection among a population of 307 pregnant women followed at the maternity of a
      community-based hospital in France (Robert Ballanger hospital in the Seine-Saint
      Denis department). The two tests compared were: Test Captia anti-HSV-1 and anti
      HSV-2 specifics IgG of Trinity Biotech and the ELISA IgG HerpesSelect 1 and 2 of
      FOCUS Diagnostics distributed by Eurobio Courtaboeuf, France. RESULTS: Both tests
      results were similar in terms of population prevalence for HSV-1 and HSV-2
      infections (respectively 86.64% and 85.99% for HSV-1; 17.59% and 15.31% for HSV
      2). Whereas the prevalence of the HSV-1 virus was described in the literature as
      being superior to our current results, the prevalence of HSV-2 according to the
      results of both ELISA tests studied was similar to the one described in previous
      cohort studies.

PMID- 19091667
TI  - [State of the art and method validations: application to fidelity performance].
AB  - Current events of clinical laboratories in France argue a lot about quality
      management. Setting up an assurance quality system can be realized in many
      approaches listed by increasing requirements: respect of reglementary Guide de
      bonne execution des analyses (GBEA), BioQualite qualification, certification and
      at last accreditation. This last step corresponds to the recognition of the
      competence of the laboratory to execute specifics tasks. Validation of methods
      used in the laboratory is a key point when you realize an accreditation package.
      Fidelity (repetability and reproductibility) is one of the parameters to check in
      your lab for quantitative methods. These performances are validated in comparison
      with targets beforehand defined (according to biological variation or state of
      the art). This article reports fidelity performances obtained in 2000 and 2006 by
      the participants to ProBioQual internal quality controls. Considering these
      performances obtained in routine conditions, the different possible approaches to
      define acceptability limits were discussed.

PMID- 19091668
TI  - [Greetings. 150th year of the Orvosi Hetilap].

PMID- 19091670
TI  - [Review of Volkmann's ischaemic contracture].
AB  - The author calls the attention, with reference to the four cases observed lately,
      to the reappearence of the Volkmann's ischaemic contracture, which was described
      at the end of the 19th century, but has been almost forgotten with the developing
      of traumatology. It discusses the reasons of development, the results and the
      treatment possibilities of the illness. It emphasizes that a non-diagnosed or non
      recognised forearm compartment syndrome which has been mistreated, can cause a
      symptom collection of different seriousness, which reduces the function of the
      hands considerably and which is difficult to handle. Prevention is considered to
      be the most important. It suggests that only an experienced specialist, who is
      familiar with hand surgery, should treat the developed contracture. It reveals
      that, differently from the classical way of its developing, nowadays the other
      etiological contractures are coming to the front. Therefore the important point
      is that not only the trauma surgeons but also the representatives of other
      disciplines should be aware of the rare syndrome which has serious consequences.

PMID- 19091669
TI  - [Early complications and their treatment after heart transplantation in Hungary-
      experience of the first 16 years].
AB  - Heart transplantation is the most successful current long-term therapy of end
      stage cardiac failure. AIM: In order to improve the results of the Hungarian
      heart transplantation activity, all data from the first 16 years were
      retrospectively examined and matched with the relevant literature. METHODS:
      Between January 1992 and December 2007, 127 heart transplantations were performed
      in 125 patients in Hungary. Above the documentation of the Department of
      Cardiovascular Surgery, Semmelweis University, the archives of the Institute of
      Forensic Medicine, Semmelweis University, the Registry of Hungarian National
      Blood Transfusion Service, Organ Coordination Office and the data of the
      Gottsegen Gyorgy National Institute of Cardiology were used. RESULTS: Early
      mortality has been approaching the international level recently. Graft failure
      was the primary cause of death in the Hungarian practice as well, followed by
      infection, uncontrollable bleeding during surgery and multiorgan failure. In one
      case successful acute retransplantation was performed, but the most effective,
      ventricular assist device therapy is completely missing from the armamentarium.
      Excellent results were achieved with medical treatment against acute rejection
      such as written in the international literature. CONCLUSIONS: For the sake of
      developing, regular usage of assist device therapy in Hungary is a prominent
      task. Development and application of standard protocols providing better quality
      in organ donor treatment and donation management have to be pressed.

PMID- 19091671
TI  - [Prophylaxis and treatment of chronic viral hepatitis as the prevention of
      hepatocellular carcinoma].
AB  - As hepatitis B and C virus (HBV, HCV) play a pivotal role in the development of
      hepatocellular carcinoma (HCC), the prophylaxis and treatment of these infections
      may mean also the prevention of HCC. The primary prevention of HCC is vaccination
      against HBV as well as the screening of blood donors for HBV and HCV markers. The
      means of secondary HCC prevention are as follows: antiviral therapy of HBV and
      HCV-related hepatitis and cirrhosis, screening ("surveillance") of cirrhotic
      patients for HCC using alpha-fetoprotein and ultrasound, and adjuvant antiviral
      treatment of HCC patients following curative tumor resection/ablation. It may be
      anticipated that the world-wide spread of HBV vaccination, the more effective
      individual treatment and novel antivirals will lead to the decrease of HCC
      incidence in the not so distant future.

PMID- 19091672
TI  - [Adverse effects of non-steroidal anti-inflammatory drugs in the lower
      gastrointestinal tract].
AB  - Non-steroidal antiinflammatory drugs (NSAID) are among the most commonly used
      drugs worldwide. Together with the beneficial effects, several adverse effects
      have become evident in the past decades. NSAIDs may damage any part of the
      gastrointestinal (GI) tract. The adverse effect in the lower GI tract was thought
      to be less important, but more and more data confirm that NSAIDs can cause
      equally severe lesions in the lower GI tract as well, only the diagnostic
      procedures are limited. NSAIDs may damage the intact mucosa, and they also may
      cause flare-up of a preexisting disease. Adverse events in the lower GI tract are
      caused mainly by the dual (COX-1 and COX-2) inhibitors. Besides the inhibiting of
      the cyclooxygenase enzymes, an important step is the local effect of the drug
      that initiates the chain reaction with the damage of the epithelial cells
      (increase of mucosal permeability, influx of luminal factors, produce of
      inflammatory mediators etc.). The spectrum of adverse effects of NSAIDs on the
      lower GI are reviewed according to the latest literature and the available
      prevention and therapeutic strategies.

PMID- 19091673
TI  - [The first epidemiologic survey among Hungarian elite athletes: eating disorders,
      depression and risk factors].
AB  - It is a fact that the incidence rate of anorexia nervosa is high among athletes
      who are considered a high-risk population in terms of eating disorders, and it is
      known as anorexia athletica by specialised literature. Our goal is to assess the
      prevalence of eating disorders among leading Hungarian athletes. PATIENTS AND
      METHODS: Before the 2008 Olympics we conducted questionnaire surveys in several
      Hungarian training camps: demographic and training data, anorexia nervosa
      inventory for self-rating (ANIS) and the bulimia investigation test, Edinburgh
      (BITE). We processed the data with the application of the SPSS software package.
      RESULTS: The average age was 22+/-4.9 years in the different sports (canoeing,
      pentathlon, handball, basketball, volleyball, weight-lifting). Average body mass
      index (22.15+/-2.12 kg/m2 ) was in the normal range. Prevalence of clinical
      anorexia nervosa was 12 (16.7%) and clinical bulimia nervosa was 5 (6.9%). The
      incidence rate of at least one pathological symptom was 73.6% with regard to the
      whole population. The prevalence of the depression episode was 37.5% by the
      current population. CONCLUSIONS: The prevalence of eating disorders among
      athletes was remarkably higher compared to the average population which, however,
      correlates with the international data. Our outcomes encourage further detailed
      researches.

PMID- 19091682
TI  - Surface force spectroscopic point load measurements and viscoelastic modelling of
      the micromechanical properties of air flow sensitive hairs of a spider
      (Cupiennius salei).
AB  - The micromechanical properties of spider air flow hair sensilla (trichobothria)
      were characterized with nanometre resolution using surface force spectroscopy
      (SFS) under conditions of different constant deflection angular velocities theta
      (rad s(-1)) for hairs 900-950 microm long prior to shortening for measurement
      purposes. In the range of angular velocities examined (4 x 10(-4) - 2.6 x 10(-1)
      rad s(-1)), the torque T (Nm) resisting hair motion and its time rate of change
      (Nm s(-1)) were found to vary with deflection velocity according to power
      functions. In this range of angular velocities, the motion of the hair is most
      accurately captured by a three-parameter solid model, which numerically describes
      the properties of the hair suspension. A fit of the three-parameter model (3p) to
      the experimental data yielded the two torsional restoring parameters, S(3p)=2.91
      x 10(-11) Nm rad(-1) and =2.77 x 10(-11) Nm rad(-1) and the damping parameter
      R(3p)=1.46 x 10(-12) Nm s rad(-1). For angular velocities larger than 0.05 rad s(
      1), which are common under natural conditions, a more accurate angular momentum
      equation was found to be given by a two-parameter Kelvin solid model. For this
      case, the multiple regression fit yielded S(2p)=4.89 x 10(-11) Nm rad(-1) and
      R(2p)=2.83 x 10(-14) Nm s rad(-1) for the model parameters. While the two
      parameter model has been used extensively in earlier work primarily at high hair
      angular velocities, to correctly capture the motion of the hair at both low and
      high angular velocities it is necessary to employ the three-parameter model. It
      is suggested that the viscoelastic mechanical properties of the hair suspension
      work to promote the phasic response behaviour of the sensilla.

PMID- 19091683
TI  - Deformable wing kinematics in the desert locust: how and why do camber, twist and
      topography vary through the stroke?
AB  - Here, we present a detailed analysis of the wing kinematics and wing deformations
      of desert locusts (Schistocerca gregaria, Forskal) flying tethered in a wind
      tunnel. We filmed them using four high-speed digital video cameras, and used
      photogrammetry to reconstruct the motion of more than 100 identified points.
      Whereas the hindwing motions were highly stereotyped, the forewing motions showed
      considerable variation, consistent with a role in flight control. Both wings were
      positively cambered on the downstroke. The hindwing was cambered through an
      'umbrella effect' whereby the trailing edge tension compressed the radial veins
      during the downstroke. Hindwing camber was reversed on the upstroke as the wing
      fan corrugated, reducing the projected area by 30 per cent, and releasing the
      tension in the trailing edge. Both the wings were strongly twisted from the root
      to the tip. The linear decrease in incidence along the hindwing on the downstroke
      precisely counteracts the linear increase in the angle of attack that would
      otherwise occur in root flapping for an untwisted wing. The consequent near
      constant angle of attack is reminiscent of the optimum for a propeller of
      constant aerofoil section, wherein a linear twist distribution allows each
      section to operate at the unique angle of attack maximizing the lift to drag
      ratio. This implies tuning of the structural, morphological and kinematic
      parameters of the hindwing for efficient aerodynamic force production.

PMID- 19091684
TI  - Critical superparamagnetic/single-domain grain sizes in interacting magnetite
      particles: implications for magnetosome crystals.
AB  - Magnetotactic bacteria contain chains of magnetically interacting crystals
      (magnetosome crystals), which they use for navigation (magnetotaxis). To improve
      magnetotaxis efficiency, the magnetosome crystals (usually magnetite or greigite
      in composition) should be magnetically stable single-domain (SSD) particles.
      Smaller single-domain particles become magnetically unstable owing to thermal
      fluctuations and are termed superparamagnetic (SP). Previous calculations for the
      SSD/SP threshold size or blocking volume did not include the contribution of
      magnetic interactions. In this study, the blocking volume has been calculated as
      a function of grain elongation and separation for chains of identical magnetite
      grains. The inclusion of magnetic interactions was found to decrease the blocking
      volume, thereby increasing the range of SSD behaviour. Combining the results with
      previously published calculations for the SSD to multidomain threshold size in
      chains of magnetite reveals that interactions significantly increase the SSD
      range. We argue that chains of interacting magnetosome crystals found in
      magnetotactic bacteria have used this effect to improve magnetotaxis.

PMID- 19091685
TI  - Sick and edgy: walk-counting as a metric of epidemic spreading on networks.
AB  - A network structure metric is herein suggested for the investigation of the
      behaviour of epidemic spreading processes in general network-structured
      populations. This simple measure, based on the algebraic powers of the adjacency
      matrix associated with the network in question, is shown to admit a heuristic
      interpretation as a representation of a spreading process similar to standard
      epidemic models. It is further shown that the values of this metric may be of use
      in understanding the dynamic pattern of epidemic spread on networks of greatly
      varying structural properties (e.g. the degree distribution, the
      assortativity/dissortativity and the clustering).

PMID- 19091686
TI  - Predicting undetected infections during the 2007 foot-and-mouth disease outbreak.
AB  - Active disease surveillance during epidemics is of utmost importance in detecting
      and eliminating new cases quickly, and targeting such surveillance to high-risk
      individuals is considered more efficient than applying a random strategy. Contact
      tracing has been used as a form of at-risk targeting, and a variety of
      mathematical models have indicated that it is likely to be highly efficient.
      However, for fast-moving epidemics, resource constraints limit the ability of the
      authorities to perform, and follow up, contact tracing effectively. As an
      alternative, we present a novel real-time Bayesian statistical methodology to
      determine currently undetected (occult) infections. For the UK foot-and-mouth
      disease (FMD) epidemic of 2007, we use real-time epidemic data synthesized with
      previous knowledge of FMD outbreaks in the UK to predict which premises might
      have been infected, but remained undetected, at any point during the outbreak.
      This provides both a framework for targeting surveillance in the face of limited
      resources and an indicator of the current severity and spatial extent of the
      epidemic. We anticipate that this methodology will be of substantial benefit in
      future outbreaks, providing a compromise between targeted manual surveillance and
      random or spatially targeted strategies.

PMID- 19091687
TI  - Hydrodynamics of sailing of the Portuguese man-of-war Physalia physalis.
AB  - Physalia physalis, commonly known as the Portuguese man-of-war (PMW), is a
      peculiar looking colony of specialized polyps. The most conspicuous members of
      this colony are the gas-filled sail-like float and the long tentacles, budding
      asymmetrically beneath the float. This study addresses the sailing of the PMW,
      and, in particular, the hydrodynamics of its trailing tentacles, the interaction
      between the tentacles and the float and the actual sailing performance. This
      paper attempts to provide answers for two of the many open questions concerning
      P. physalis: why does it need a sail? and how does it harness the sail?

PMID- 19091688
TI  - Mechanisms and behavioural functions of structural coloration in cephalopods.
AB  - Octopus, squid and cuttlefish are renowned for rapid adaptive coloration that is
      used for a wide range of communication and camouflage. Structural coloration
      plays a key role in augmenting the skin patterning that is produced largely by
      neurally controlled pigmented chromatophore organs. While most iridescence and
      white scattering is produced by passive reflectance or diffusion, some
      iridophores in squid are actively controlled via a unique cholinergic, non
      synaptic neural system. We review the recent anatomical and experimental evidence
      regarding the mechanisms of reflection and diffusion of light by the different
      cell types (iridophores and leucophores) of various cephalopod species. The
      structures that are responsible for the optical effects of some iridophores and
      leucophores have recently been shown to be proteins. Optical interactions with
      the overlying pigmented chromatophores are complex, and the recent measurements
      are presented and synthesized. Polarized light reflected from iridophores can be
      passed through the chromatophores, thus enabling the use of a discrete
      communication channel, because cephalopods are especially sensitive to polarized
      light. We illustrate how structural coloration contributes to the overall
      appearance of the cephalopods during intra- and interspecific behavioural
      interactions including camouflage.

PMID- 19091690
TI  - The comparative phylogeography of east coast estuarine fishes in formerly
      glaciated sites: Persistence versus recolonization in Cyprinodon variegatus
      ovinus and Fundulus heteroclitus macrolepidotus.
AB  - Species distributions may be dramatically affected by climatic variability, such
      as occurred during Pleistocene glaciation. Populations of coastal organisms could
      have been affected directly by ice movement or through sea level change. Response
      could involve shifts in distribution southwards or persistence through the full
      range or in limited high-latitude refugia. Comparative studies of the response of
      ecologically similar species can provide a useful complement to those examining
      response across disparate species in defining what parameters influence
      persistence. Patterns of mitochondrial genetic variation in 2 estuarine fish
      subspecies from the Northwest Atlantic, Fundulus heteroclitus macrolepidotus and
      Cyprinodon variegatus ovinus, indicate that ecological similarity does not
      necessarily predict propensity for glacial persistence. Fundulus heteroclitus
      macrolepidotus is highly diverse in glaciated regions, with isolated populations
      whose origins predate the last glacial maximum and may have recently expanded
      it's range to the south from New England. However, within glaciated regions,
      signals of population growth and distributional shifts indicate a dynamic
      Pleistocene history for F. h. macrolepidotus, in contrast with recent studies
      involving microsatellites. A different pattern is found in C. v. ovinus, which is
      depauperate in formerly glaciated sites, with a clear signal of recent
      recolonization of glaciated regions from the south. Genetic differentiation in
      glaciated areas is consistent with isolation after glacial withdrawal. In C. v.
      ovinus, rapidly evolving microsatellite loci show a similar pattern to
      mitochondrial DNA but may be reaching equilibrium on small spatial scales. These
      contrasting patterns of variation illustrate how ecologically similar species can
      respond to large-scale environmental change in distinct ways.

PMID- 19091691
TI  - Sharing the good, sharing the bad: the benefits of emotional self-disclosure
      among middle-aged and older adults.
AB  - OBJECTIVE: The present study was designed to assess the impact of experimentally
      manipulating positive and negative self-disclosure on three domains of well-being
      among healthy middle-aged and older adults: emotional, psychological, and
      physical. METHOD: Using a modified self-disclosure paradigm for sad, mixed (sad
      and happy), and neutral content, the authors examine changes in depressive
      symptomatology, stress, sad and happy mood, and self-reported health across 4
      weeks in a sample (N = 200) of African American and European American men and
      women (age M = 54 years). RESULTS: Consistent with research on younger groups,
      health symptomatology declined over time (irrespective of condition). However,
      although African Americans reported reductions in stress and depressive
      symptomatology in the sad condition, European Americans experienced similar
      reductions only in the neutral condition. DISCUSSION: Results are discussed in
      terms of applications of the self-disclosure paradigm to developmentally and
      ethnically diverse groups.

PMID- 19091689
TI  - POLAR MAPPER: a computational tool for integrated visualization of protein
      interaction networks and mRNA expression data.
AB  - Polar Mapper is a computational application for exposing the architecture of
      protein interaction networks. It facilitates the system-level analysis of mRNA
      expression data in the context of the underlying protein interaction network.
      Preliminary analysis of a human protein interaction network and comparison of the
      yeast oxidative stress and heat shock gene expression responses are addressed as
      case studies.

PMID- 19091692
TI  - The effects of socioeconomic status on participation in care among middle-aged
      and older adults.
AB  - OBJECTIVE: This study assesses the effects of socioeconomic status (education and
      poverty) on seeking health information and subsequent use of this information
      during the medical encounter. METHOD: Data on 19,944 adults (aged 45 and older)
      were drawn from the 2000-2001 Household Component of the Community Tracking
      Study, a nationally representative survey of non-institutionalized individuals.
      RESULTS: Higher levels of education were associated with a greater likelihood of
      seeking health information and mentioning information to physicians. The poor and
      near poor were less likely to seek health information, but only the near poor
      were significantly less likely to mention information to the physician.
      DISCUSSION: These findings underscore the importance of education in the
      acquisition and use of health information among middle-aged and older adults.

PMID- 19091693
TI  - Ontologies of cellular networks.
AB  - As part of a series of workshops on different aspects of biomedical ontology
      sponsored by the National Center for Biomedical Ontology (NCBO), a workshop
      titled "Ontologies of Cellular Networks" took place in Newark, New Jersey, on 27
      to 28 March 2008. This workshop included more than 30 participants from various
      backgrounds in biomedicine and bioinformatics. The goal of the workshop was to
      provide an introduction to the basic tools and methods of ontology, as well as to
      enhance coordination between groups already working on ontologies of cellular
      networks. The meeting focused on three questions: What is an ontology? What is a
      pathway? What is a cellular network?

PMID- 19091695
TI  - Oral detection of short-, medium-, and long-chain free fatty acids in humans.
AB  - There is increasing evidence supporting an oral chemosensory detection system for
      free fatty acids (FFA). The presumptive transduction mechanisms have different
      ligand specificities. Psychophysical studies with FFA varying in chain length and
      saturation may aid in identifying the presence and functionality of these
      mechanisms in humans. Oral detection thresholds were measured for linoleic,
      stearic, lauric, and caproic acids in 32 healthy adults by an ascending, 3
      alternative, forced-choice, sip and spit procedure. Thresholds were obtained for
      all fatty acids from all participants, but the distributions were wide and
      nonnormal. Thresholds were not correlated between fatty acids nor with thresholds
      for sucrose (taste), butanol (olfactory), mineral oil, or gum acacia (both
      somatosensory). These data demonstrate human oral sensitivity to short-, medium-,
      and long-chain FFA and suggest the presence of multiple transduction mechanisms.
      The findings are consistent with, but do not definitively demonstrate, a role for
      taste that may have a genetic basis.

PMID- 19091696
TI  - The morphological change of supporting cells in the olfactory epithelium after
      bulbectomy.
AB  - Transmission electron microscopy was used to study the responses of the
      supporting cells of the olfactory epithelium at 1-5 days after surgical ablation
      of the olfactory bulb (bulbectomy). In intact olfactory epithelium, lamellar
      smooth endoplasmic reticulum and rod-shaped mitochondria were distinctly observed
      in the supporting cells. On the first day after bulbectomy, bending of the
      microvilli and an increase in the smooth endoplasmic reticulum were observed.
      Cristae of the mitochondria became obscure, and the density of the mitochondrial
      matrix decreased. On the second day after bulbectomy, the number of microvilli
      decreased, broad cytoplasmic projections that contained cytoplasmic organelles
      protruded into the luminal side, and the mitochondria were swollen. On the fifth
      day after bulbectomy, microvilli seemed to be normal and some cells had large
      cytoplasmic projections that protruded toward the lumen of the nasal cavity.
      Within the cytoplasmic projections of the supporting cells, a large lamellar and
      reticular-shaped smooth endoplasmic reticulum was evident. Mitochondria exhibited
      almost normal morphology. The current findings demonstrate that morphological
      changes occur in the supporting cells after bulbectomy. This new evidence
      hypothesizes that these changes represent events that contribute to the
      regeneration of the olfactory epithelium after bulbectomy.

PMID- 19091697
TI  - Influences of food-name labels on perceived tastes.
AB  - We examined whether food identity information presented as name labels would
      influence perception of basic tastes. To test this hypothesis, we used 10 aqueous
      taste solutions consisting of 2-3 of the 5 basic tastes in different ratios and
      presented them with one of these food names: "lemon," "coffee jelly," "caramel
      candy," and "consomme soup." Forty-six participants tasted samples presented with
      either food-name labels or random number labels. We found that participants who
      tasted samples with food-name labels rated tastes with significantly higher
      liking and familiarity scores than those presented with random numbers,
      especially when the names and tastes were perceived as being congruent. Though an
      effect on perceived intensity was not as prominent, we observed cases in which
      intensity ratings significantly changed. Effects of identity information have
      been shown in olfaction and flavors. This study demonstrates the first
      experimental evidence that identity information given as names also influence the
      perception of unimodal basic tastes.

PMID- 19091698
TI  - Myeloperoxidase, modified lipoproteins, and atherogenesis.
AB  - Numerous lines of evidence implicate a role for myeloperoxidase (MPO) in the
      pathogenesis of atherosclerosis. Enriched within vulnerable plaque, MPO serves as
      an enzymatic source of eicosanoids and bioactive lipids and generates atherogenic
      forms of both low- and high-density lipoproteins. These factors likely contribute
      to clinical studies demonstrating that increased systemic levels of MPO and its
      oxidation products predict increased cardiovascular risk. As a result, interest
      has focused on the potential to target MPO for the development of new risk
      markers, imaging, and therapies to prevent cardiovascular events.

PMID- 19091699
TI  - Paraoxonase 2 attenuates macrophage triglyceride accumulation via inhibition of
      diacylglycerol acyltransferase 1.
AB  - This study questioned the role of paraoxonase 2 (PON2) in attenuation of
      macrophage lipids accumulation. Mouse peritoneal macrophages (MPMs) harvested
      from PON2-deficient mice versus control C57BL/6 mice, look like foam cells and
      were larger in size and filled with lipid droplets. Macrophage triglyceride (but
      not cholesterol) content, biosynthesis rate, and microsomal acyl
      CoA:diacylglycerol acyltransferase 1 (DGAT1) activity (not mRNA and protein) in
      PON2-deficient versus control MPM were all significantly increased by 4.6-, 3.6-,
      and 4.4-fold, respectively. Similarly, microsomal DGAT1 activity and cellular
      triglyceride content were significantly decreased in human PON2-transfected cells
      as well as upon incubation of PON2-deficient MPM with recombinant PON2. In all
      the above experimental systems, PON2 also decreased macrophage oxidative state.
      Incubation of PON2-deficient MPM with the free radicals generator 2,2'
      amidinopropane hydrochloride increased cellular oxidative stress and DGAT1
      activity by 2.2- and 3.4-fold, respectively, whereas incubation of microsomes
      from PON2-deficient MPM with superoxide dismutase decreased DGAT1 activity by
      40%. We thus conclude that PON2 attenuates macrophage triglyceride accumulation
      and foam cell formation via inhibition of microsomal DGAT1 activity, which
      appears to be sensitive to oxidative state.

PMID- 19091700
TI  - Modulation of paraoxonase 1 and 3 expression after moderate exercise training in
      the rat.
AB  - Paraoxonases (PONs) are a small family of antioxidant enzymes whose
      antiatherogenic activity is well known. The aim of the present study was the
      evaluation of the effects of moderate aerobic training on their expression using
      a rat model. In order to discriminate between PON1 and PON3 enzymatic activity,
      we took advantage of some differences in their substrate preferences. PON1 and
      PON3 enzymatic activities and their protein levels were analyzed in plasma and in
      liver microsomes, and their mRNA levels in the liver. Exercise training did not
      affect PON1 expression or enzymatic activity but increased PON3 mRNA, protein
      levels, and enzymatic activity. Training also induced variations in plasma
      membrane composition, including an increase in polyunsaturated and a decrease in
      mono- and di-unsaturated fatty acids. On the other hand, acute exercise inhibited
      PON activities while increasing PON3 protein content in liver microsomes and
      reversing the relative composition in mono-, di-, and poly-unsaturated fatty
      acids, suggesting that physical stress, by altering membrane composition, may
      impair PON release from liver membranes. In conclusion, we documented, for the
      first time, the presence of PON3 in rat serum and, notably, found that the
      upregulation of PON3, rather than PON1, appears to be associated with physical
      training.

PMID- 19091701
TI  - Statins and cognitive function.

PMID- 19091702
TI  - Deterioration after Guillain-Barre syndrome: recurrence, treatment-related
      fluctuation or CIDP?

PMID- 19091703
TI  - Psychogenic aphonia: spectacular recovery after motor cortex transcranial
      magnetic stimulation.

PMID- 19091704
TI  - Immunosuppressant drugs for myasthenia gravis.
AB  - Along with corticosteroids, immunosuppressant drugs are mainstays of disease
      modifying therapy for myasthenia gravis (MG). However, their efficacies and
      optimum use are unclear. We identified seven randomised controlled trials (RCT)
      of immunosuppressants in generalised MG that qualified for Cochrane Review: (1)
      azathioprine plus initial prednisolone versus prednisolone; (2) azathioprine plus
      prednisolone versus prednisolone plus placebo; (3) ciclosporin versus placebo (4)
      ciclosporin plus prednisolone versus prednisolone plus placebo; (5)
      cyclophosphamide plus prednisolone versus prednisolone plus placebo; (6)
      mycophenolate mofetil (MMF) alone or plus either ciclosporin or prednisolone
      versus placebo alone or plus either ciclosporin or prednisolone; (7) tacrolimus
      plus corticosteroids with or without plasma exchange versus corticosteroids with
      or without plasma exchange. All trials were small (14 to 41 participants) and
      their designs heterogeneous. The RCT evidence, albeit limited, was that
      ciclosporin (alone or with corticosteroids) or cyclophosphamide (with
      corticosteroids) improved MG significantly within 1 year compared with placebo.
      There was no clear evidence of benefit for azathioprine, MMF, or tacrolimus
      within 1 year. Larger, better-designed, longer trials are needed.

PMID- 19091706
TI  - A systematic review of Instrumental Activities of Daily Living scales in
      dementia: room for improvement.
AB  - BACKGROUND: Instrumental Activities of Daily Living (IADL) questionnaires can be
      helpful in diagnosing dementia and are often used for clinical follow-up and
      treatment evaluation in dementia patients. Despite the large number of
      questionnaires, their quality has received little attention. OBJECTIVE: To
      systematically review the measurement properties of all available structured
      informant-based (I)ADL questionnaires, developed or validated for use in demented
      patients. METHODS: A systematic literature search was conducted in MEDLINE,
      PsycINFO and EMBASE for psychometric articles on (I)ADL questionnaires. In
      addition, reference lists of all retrieved articles were screened. Standardised
      criteria were used to assess the quality of the measurement properties. When
      possible, investigators were contacted to obtain missing information. Two authors
      independently extracted studies and performed the quality assessment of the
      questionnaires. FINDINGS: Thirty-two articles were selected, covering 12 (I)ADL
      questionnaires. Information on 52.3% of the quality aspects was not available,
      32.4% of the ratings were indeterminate, 8.1% were positive, and 7.2% were
      negative. Out of eight measurement properties, two scales (the DAD and the
      Bristol ADL) received two positive ratings and were classified as of moderate
      quality. Five scales (ADL-PI, ADL-IS, B-ADL, CSADL and Lawton IADL) received one
      positive rating. INTERPRETATION: The findings indicate that improvements in and
      more data on psychometric properties of (I)ADL questionnaires for dementia
      patients are necessary in order to justify their use.

PMID- 19091707
TI  - Neurological picture. Spinal cord involvement in posterior reversible
      encephalopathy syndrome.

PMID- 19091708
TI  - Neurological picture. Extreme unilateral widening of Virchow-Robin spaces
      mimicking stroke.

PMID- 19091709
TI  - Neurological picture. A case of Pourfour du Petit syndrome following tumour
      surgery of the mandible.

PMID- 19091710
TI  - Birdsey Renshaw (1911-1948) and his eponym.

PMID- 19091711
TI  - Neurophysiological evidence for cerebellar dysfunction in primary focal dystonia.
AB  - Recent studies have suggested that there may be functional and structural changes
      in the cerebellum of patients with adult onset primary focal dystonia. The aim of
      this study was to establish whether there is any neurophysiological indicator of
      abnormal cerebellar function, using the classic eyeblink conditioning paradigm.
      This paradigm at short intervals is dependent on the olivo-cerebellar circuit and
      does not require cerebral and basal ganglia structures. Eyeblink conditioning was
      performed by pairing an auditory tone with a supraorbital nerve stimulus with a
      delay interval of 400 ms in 12 patients with primary focal dystonia (seven
      cervical dystonias, five focal hand dystonias) and eight healthy controls.
      Healthy controls produced more conditioned eyeblink responses than patients with
      focal dystonia, indicating an abnormality of associative learning in this patient
      population. This study provides neurophysiological evidence for functional
      changes in the olivo-cerebellar pathway of patients with primary focal dystonia.
      Further work needs to be done to determine if these changes are primary,
      secondary or epiphenomenal to the disease.

PMID- 19091712
TI  - Cause of death and clinical grading criteria in a cohort of amyotrophic lateral
      sclerosis cases undergoing autopsy from the Scottish Motor Neurone Disease
      Register.
AB  - BACKGROUND: The Scottish Motor Neurone Disease Register is a population based
      register of amyotrophic lateral sclerosis/motor neurone disease (ALS/MND) in
      Scotland, with high case ascertainment levels. OBJECTIVE: To investigate the
      cause of death by autopsy and assess grading criteria in a cohort of cases of ALS
      from the Scottish MND Register. METHODS: The records of 44 patients undergoing
      autopsy were reviewed to determine the cause of death, clinical assessment (El
      Escorial and modified World Federation of Neurology criteria) during life and
      neuropathological autopsy findings. RESULTS: In a cohort of 44 cases undergoing
      autopsy between 1989 and 1998, the cause of death could be directly or indirectly
      (bronchopneumonia, aspiration/pneumonia and respiratory failure) attributed to
      MND in 32/44 (73%) cases. The clinical diagnosis of MND was confirmed at autopsy
      in 44/44 (100%) cases, 3/44 (7%) cases showed coexistent neurodegenerative
      disease and 5/44 (11%) were familial MND cases. CONCLUSIONS: Within our cohort,
      MND contributes to death in the majority of cases and there is excellent
      clinicopathological correlation, irrespective of the clinical grading criteria
      used. However, the autopsy rate is low (4%) and further larger studies are
      required to identify heterogeneity within the disease.

PMID- 19091713
TI  - Neurological picture. "Malignant" ischaemic stroke of an entire cerebral
      hemisphere.

PMID- 19091714
TI  - Mobility and falls in people with Huntington's disease.
AB  - OBJECTIVE: The aim of this study was to estimate the frequency of falls in people
      with Huntington's disease (HD) and make a preliminary assessment of tools
      appropriate for assessing the risk of falling. DESIGN: Observational study.
      SETTING: Hospital clinic. SUBJECTS: 24 people with HD. MAIN MEASURES: Balance was
      assessed using the Berg Balance Scale (BBS) and Timed "Up & Go" (TUG) test.
      Walking speed over 10 m was recorded. Long-term monitoring of walking activity
      was undertaken. Unified Huntington Disease Rating Scale (UHDRS) motor, Functional
      Assessment Scale (FAS), Independence Scale (IS) and Total Functional Capacity
      (TFC) scores were obtained as well as data about falls and stumbles. Differences
      between "recurrent fallers" (>or=2 falls/year) and "non-fallers" (<or=1
      fall/year) for the range of outcome measures were investigated and probabilities
      calculated. RESULTS: Mean (SD) age (years) of people with HD (n = 24) tested was
      56.6 (11.7) and BMI (kg/m(2)) 24.7 (5.5). Median (range) UHDRS motor scores were
      48 (28-80). Ten (41.6%) patients reported <or=1 fall and 14 (58.3%) >or=2 falls
      in the previous 12 months. Recurrent fallers walked less (p<0.01) and slower than
      non-fallers. Their balance (BBS) (p<0.01) was worse and TUG scores were higher
      (p<0.01). People with HD had increased risk of falls if TUG scores were >or=14 s
      or BBS scores <or=40. CONCLUSION: A high proportion of HD patients have recurrent
      falls, and the BBS and TUG appear to be useful in falls risk assessment.

PMID- 19091715
TI  - Dental injury during seizures associated with juvenile myoclonic epilepsy.
AB  - BACKGROUND: Patients can sustain injuries during seizures and the pattern and
      type of injury (eg, tongue biting) can be a useful silent witness in the
      diagnosis of seizures. In addition, the seizure type potentially influences the
      type of injury. METHODS: Patients with dental injury were identified from the
      Gloucestershire Epilepsy Database (n = 1673). These patients' notes were reviewed
      and the following data collected: demographic data; seizure types and age of
      onset; injury; EEG; and MRI. RESULTS: 14 people had dental injuries: 10 incisors
      (seven had >1 incisor) and five other teeth. Eight had juvenile myoclonic
      epilepsy (JME), two other primary generalised epilepsy and four focal onset
      epilepsy. Compared with the rest of the database population (JME; n = 81) there
      was a highly significant association of dental injury with JME (p<0.0001).
      CONCLUSIONS: Incisor injury is rare but appears to be associated with JME in
      patients with epilepsy, presumably reflecting the pattern of seizure onset. This
      pattern of injury should prompt consideration of this diagnosis. It is hoped that
      recognition of this can both facilitate earlier diagnosis and help educate
      patients to protect their teeth.

PMID- 19091716
TI  - Late-onset Tay-Sachs disease presenting as a childhood stutter.

PMID- 19091717
TI  - Psychogenic aphonia: spectacular recovery after motor cortex transcranial
      magnetic stimulation.

PMID- 19091718
TI  - Effect of steroid treatment in cerebellar ataxia associated with anti-glutamic
      acid decarboxylase antibodies.

PMID- 19091722
TI  - The single mitochondrial porin of Trypanosoma brucei is the main metabolite
      transporter in the outer mitochondrial membrane.
AB  - All mitochondria have integral outer membrane proteins with beta-barrel
      structures including the conserved metabolite transporter VDAC (voltage dependent
      anion channel) and the conserved protein import channel Tom40. Bioinformatic
      searches of the Trypanosoma brucei genome for either VDAC or Tom40 identified a
      single open reading frame, with sequence analysis suggesting that VDACs and
      Tom40s are ancestrally related and should be grouped into the same protein
      family: the mitochondrial porins. The single T. brucei mitochondrial porin is
      essential only under growth conditions that depend on oxidative phosphorylation.
      Mitochondria isolated from homozygous knockout cells did not produce adenosine
      triphosphate (ATP) in response to added substrates, but ATP production was
      restored by physical disruption of the outer membrane. These results demonstrate
      that the mitochondrial porin identified in T. brucei is the main metabolite
      channel in the outer membrane and therefore the functional orthologue of VDAC. No
      distinct Tom40 was identified in T. brucei. In addition to mitochondrial
      proteins, T. brucei imports all mitochondrial tRNAs from the cytosol. Isolated
      mitochondria from the VDAC knockout cells import tRNA as efficiently as wild
      type. Thus, unlike the scenario in plants, VDAC is not required for mitochondrial
      tRNA import in T. brucei.

PMID- 19091721
TI  - Aerobic exercise for alcohol recovery: rationale, program description, and
      preliminary findings.
AB  - Alcohol use disorders are a major public health concern. Despite the demonstrated
      efficacy of a number of different treatments for alcohol dependence, relapse
      remains a major problem. Healthy lifestyle changes may contribute to long-term
      maintenance of recovery, and interventions targeting physical activity, in
      particular, may be especially valuable as an adjunct to alcohol treatment. In
      this article, the authors discuss the rationale and review potential mechanisms
      of action whereby exercise might benefit alcohol dependent patients in recovery.
      They then describe the development of a 12-week moderate-intensity aerobic
      exercise program as an adjunctive intervention for alcohol dependent patients in
      recovery. Preliminary data from a pilot study (N=19) are presented, and the
      overall significance of this research effort is discussed.

PMID- 19091724
TI  - Ethical and cultural considerations in delivering psychiatric diagnosis:
      reconciling the gap using MDD diagnosis delivery in less-acculturated Chinese
      patients.
AB  - Talking to patients from diverse cultural backgrounds about their psychiatric
      disorders requires knowledge of one's own culture, the patients' cultures, and
      the ways in which they might interact, both in positive and unexpectedly negative
      ways. In this paper, we discuss the issues raised by discussing psychiatric
      diagnoses with Chinese-Americans who hold traditional illness beliefs and are not
      familiar with Western conceptions of psychiatric disorders. We explore how
      cultural values influence this aspect of medical practice, and suggest practical
      approaches to communicating the diagnosis of major depressive disorder in a
      culturally sensitive manner. Our clinical approach is to develop co-constructed
      illness narratives with patients, and to aid this process by reframing different
      elements of the clinical process into more culturally resonant forms. The
      following steps are suggested: 1) elicit patient's illness beliefs; 2) understand
      and acknowledge multiple explanatory models; 3) contextualize depressive symptoms
      into patient's physical health and social system; 4) introduce Western
      psychiatric theories in ways that reflect assumptions shared by Traditional
      Chinese Medicine (TCM); 5) involve patients' families whenever possible; and 6)
      use terminology that avoids unintended stigma.

PMID- 19091723
TI  - Gene expression levels are a target of recent natural selection in the human
      genome.
AB  - Changes in gene expression may represent an important mode of human adaptation.
      However, to date, there are relatively few known examples in which selection has
      been shown to act directly on levels or patterns of gene expression. In order to
      test whether single nucleotide polymorphisms (SNPs) that affect gene expression
      in cis are frequently targets of positive natural selection in humans, we
      analyzed genome-wide SNP and expression data from cell lines associated with the
      International HapMap Project. Using a haplotype-based test for selection that was
      designed to detect incomplete selective sweeps, we found that SNPs showing
      signals of selection are more likely than random SNPs to be associated with gene
      expression levels in cis. This signal is significant in the Yoruba (which is the
      population that shows the strongest signals of selection overall) and shows a
      trend in the same direction in the other HapMap populations. Our results argue
      that selection on gene expression levels is an important type of human
      adaptation. Finally, our work provides an analytical framework for tackling a
      more general problem that will become increasingly important: namely, testing
      whether selection signals overlap significantly with SNPs that are associated
      with phenotypes of interest.

PMID- 19091725
TI  - When providers and patients come from different backgrounds: perceived value of
      additional training on ethical care practices.
AB  - Fostering the therapeutic alliance, safeguarding confidentiality, gaining
      informed consent, and enhancing treatment adherence are critical aspects of
      patient care. We examined whether multidisciplinary health care providers
      perceive additional training on these areas as helpful in their work with
      patients from different ethnic backgrounds than the provider. Data are drawn from
      a National Institute on Drug Abuse-funded survey of 1555 providers in 8
      disciplines in New Mexico and Alaska. Clinicians viewed additional training as
      moderately helpful for ensuring treatment adherence, establishing the therapeutic
      alliance, safeguarding confidentiality, and engaging in informed consent
      processes, in that order. Women were more receptive than men to additional
      training. Modest differences were detected between behavioral and physical health
      providers and between minority and majority providers. Implications of providers'
      only modest interest in such training are discussed.

PMID- 19091726
TI  - Adapting the SRQ for Ethiopian populations: a culturally-sensitive psychiatric
      screening instrument.
AB  - The objective of the study was to develop a culturally sensitive psychiatric
      screening instrument valid for Ethiopians in Ethiopia and Israel. The study
      sample was composed of 356 Amharic-speaking Ethiopians from Ethiopia and Israel,
      aged 18-55, divided into three groups: i) general population; ii) people in non
      psychiatric treatment; iii) people in psychiatric treatment. They were
      interviewed with the Self-Reporting Questionnaire (SRQ), modified to include 10
      culturally specific items, and the Brief Psychiatric Research Scale (BPRS) as a
      criterion of psychopathology. Physicians also completed an encounter form about
      the presence of mental health symptoms in participants. To make the questions
      more culturespecific, the translation of 12 items on the SRQ was changed. The
      content, construct, and criterion validity of each question were also examined,
      leading to the deletion of five items. The validity of the revised instrument
      (SRQ-F) was superior to that of the original instrument (SRQ). This study
      demonstrates the need for psychiatric screening instruments to be adapted to
      different cultures by incorporating meaningful translations and adding culturally
      specific items.

PMID- 19091727
TI  - The quest for recognition: Brazilian immigrants in the United States.
AB  - 'Hispanic' and 'Latino' are imprecise umbrella terms often used in the United
      States to designate nationals from Central and South America. The labelling of
      Brazilians in this manner generates inaccurate demographic information, including
      a significant undercount of the migrant population. Research data indicates that
      Brazilians object to being designated Hispanics, since Brazilians speak
      Portuguese and have no Spanish heritage. The labelling of ethnic groups has been
      criticized as a stereotypical and racist system, which primarily responds to non
      scientific demands. This commentary appeals for reform in the way researchers and
      institutions refer to minority citizens as well as for continued research to
      investigate racism and ethnic prejudice. The development of new approaches and
      methodologies to examine social networks, migration and the geographic
      concentration of poverty is advocated.

PMID- 19091728
TI  - Daily stressors, war experiences, and mental health in Afghanistan.
AB  - Working in Afghanistan's capital city of Kabul, the authors assessed the relative
      contribution of daily stressors and war-related experiences of violence and loss
      to levels of depression, PTSD, impaired functioning, and a culturally specific
      measure of general psychological distress. For women, daily stressors were a
      better predictor than war experiences of all mental health outcomes except for
      PTSD; for men, daily stressors were a better predictor of depression and
      functional impairment, while war experiences and daily stressors were similarly
      predictive of general distress. For men, daily stressors moderated the
      relationship between war experiences and PTSD, which was significant only under
      conditions of low daily stress. The study's implications for research and
      intervention in conflict and post-conflict settings are considered.

PMID- 19091729
TI  - The experience of 'mental trauma' and its transcultural application.
AB  - Approaches to the mental health care of refugees and disaster survivors have
      recently been subject to sustained critique. This article critically examines the
      notion of ;mental trauma' as it has been used by psychosocial intervention
      programmes addressing the aftermath of the 2004 Asian tsunami. The objective is
      to shed light on the guidelines' implicit and explicit assumptions about how
      people are expected to act and feel after a disaster, thereby implying a certain
      'metaphysic' of emotional experience. It will be argued that feelings can not be
      separated from intersubjective and public spheres, for they shape and motivate
      expression and experience. Instead, it is necessary to explore the particular
      ways in which cultural meaning and social structure relate to discourses and
      practices through which suffering is produced and represented. To conclude, a
      method is outlined to operationalize particular experiences of suffering and the
      institutionalized discourses and practices in which they obtain social meaning
      and force.

PMID- 19091730
TI  - Cultural factors in the diagnosis and treatment of traumatised migrant patients
      from Turkey.
AB  - The process of migration may be associated not only with great hope, but also
      with distressing experiences that can lead to trauma and posttraumatic stress
      disorders. Although some of the symptoms induced by trauma are common across
      cultures, the strategies used to deal with them are often culture-specific. In
      the following paper, we consider the unique aspects of trauma-focused
      psychotherapy in patients with a history of migration. We discuss a variety of
      culture-specific factors with the help of two case histories.

PMID- 19091731
TI  - Arab culture and mental health care.
AB  - This selective review describes recent literature and the author's experience
      with mental illness and mental health care, and the impact of cultural
      transformation on mental health in some Arab Islamic cultures, particularly in
      Egypt, Qatar and Kuwait. Traditional extended Arab families provide a structure
      for their members that may sometimes prevent and or compensate for the effects of
      parental loss and mental disability. The role of traditional families in the care
      of members and in medical decision-making is discussed. The impact of cultural
      change on Arab culture is also examined, as is the effect of intergenerational
      conflict in traditional families.

PMID- 19091732
TI  - Karo-kari: a form of honour killing in pakistan.
AB  - Karo-Kari is a type of premeditated honour killing, which originated in rural and
      tribal areas of Sindh, Pakistan. The homicidal acts are primarily committed
      against women who are thought to have brought dishonour to their family by
      engaging in illicit pre-marital or extra-marital relations. In order to restore
      this honour, a male family member must kill the female in question. We conducted
      a systematic review of the published literature other sources on karo-kari and
      related forms of honour killing or violence against women. Media and non
      governmental organization reports were utilized for case studies and analysis.
      Although legally proscribed, socio-cultural factors and gender role expectations
      have given legitimacy to karo-kari within some tribal communities. In addition to
      its persistence in areas of Pakistan, there is evidence that karo-kari may be
      increasing in incidence in other parts of the world in association with
      migration. Moreover, perpetrators of ;honour killings' often have motives outside
      of female adultery. Analysis of the socio-cultural and psycho-pathological
      factors associated with the practice of karo-kari can guide the development of
      prevention strategies.

PMID- 19091733
TI  - Ramadan fasting triggering koro-like symptoms during acute alcohol withdrawal: a
      case report from Oman.
AB  - This article describes a case of koro-like symptoms from Oman associated with
      alcohol withdrawal and illustrates how the socio-cultural practices of Ramadan
      fasting affected the patterning and timing of presentation of severe alcohol
      withdrawal symptoms. The patient was severely distressed by the delusion that his
      penis had been amputated. The acute anxiety involving this delusion appears to be
      conceptually and phenomenologically similar to koro.

PMID- 19091734
TI  - The role of surgery in the management of pleuropulmonary tuberculosis - seven
      years' experience at a single institution.
AB  - Pleuropulmonary tuberculosis (TB) is a relatively frequent condition (the
      incidence of (TB) was 176/100,000 in our county in 2004) and some of these
      patients with TB are undergoing surgical interventions. The authors share their
      experience in surgical treatment of pleuropulmonary tuberculosis, based on
      minimal invasive techniques such as VATS and filling the residual cavities with
      muscle or skin-muscle grafts. The authors are retrospectively revising 144
      patients between 1 January 2001 and 31 December 2007 who underwent surgical
      treatment for tuberculosis in this period. Two hundred and thirteen surgical
      procedures were performed for pleuropulmonary tuberculosis, representing 4% of
      all the procedures done in the department. For most of the patients the
      etiological diagnosis was not established until the operations, all the patients
      were sputum-negative. The diagnoses at the admittance were: pulmonary nodules or
      tumors (42 patients), pleural collections (46), pleural thickening and post
      tuberculosis syndromes (46), fibrocavitary tuberculosis (6), and tuberculous
      pericarditis (4). Of all the procedures applied, 14 were pulmonary resections, 50
      atypical (wedge) resections, 70 video-assisted thoracic surgery (VATS)
      procedures, and nine patients needed muscle or skin-musle flap for residual
      pleural cavities. Eleven patients (7.6%) had to undergo secondary surgery due to
      complications. No in-hospital mortality was registered. The mean hospitalisation
      period was 10.1+/-4.2 (S.D.) days.

PMID- 19091735
TI  - The relative responsiveness and construct validity of the Spanish version of the
      DASH instrument for outcomes assessment in open carpal tunnel release.
AB  - The objective of this study was to evaluate the responsiveness and construct
      validity of the Spanish version of the DASH as outcome measure for carpal tunnel
      surgery. The study population was 42 patients with the diagnosis of carpal tunnel
      syndrome (CTS) based on clinical and electrophysiological criteria. The clinical
      design was a classic Cohort study with measures the day before and 12 weeks after
      open carpal tunnel release. The Spanish version of the DASH was compared to the
      physical exam measures as dexterity time, grip and pinch strength, range of
      motion of the wrist (ROM) and two-point discrimination (2PPD). The responsiveness
      was evaluated based on the effect size (ES) and the standardised response means
      (SRM). The Spanish version of the CTS questionnaire (CTQ) and the Spanish version
      of the 36-item short-form health survey (SF-36) were self-administered to the
      same study population and followed the same clinical design. The hypothesis that
      the DASH instrument should present a responsiveness level higher than the SF-36
      and lower than the CTQ was established to demonstrate the construct validity. The
      DASH instrument showed an ES of 0.68 and an SRM of 1.00. Responsiveness of
      traditional physical exam measures were lower, running from 0.35 (SRM) for
      dexterity time to 0.00 (ES) for key pinch strength. The SF-36 presented a
      responsiveness level (range from 0.07 to 0.14) lower that the DASH. The CTQ
      showed the highest level of responsiveness (ES = 1.41 and 0.7) (SRM = 1.75 and
      0.51). In conclusion, The DASH instrument is more sensitive in detecting clinical
      change than the physical exam measures for use in clinical outcome studies of CTS
      done at 12 weeks after surgery. The Spanish DASH showed a responsiveness lower
      than the CTQ and higher than the SF-36 as a proof of a good construct validity.

PMID- 19091736
TI  - Osseointegrated finger prostheses.
AB  - Amputation of a digit can lead to functional and psychological problems and
      patients can benefit from digital prostheses. Unfortunately, standard prostheses
      are often unstable, particularly when fitted over short amputation stumps.
      Prosthesis fixation by osseointegration is widely used in oral and extraoral
      applications and may help avoid the problem of instability. This paper reports
      the results of four patients with five finger amputations who were treated with
      osseointegrated implants to attach finger prostheses. One implant failed to
      osseointegrate and the procedure was abandoned. Three patients were successfully
      treated to completion of three finger prostheses and are extremely satisfied with
      their outcomes, both cosmetically and functionally, with osseoperception reported
      by all three patients.

PMID- 19091737
TI  - A modification of the Chinese island flap technique for simple incomplete
      syndactyly release.
AB  - This paper presents a modification of the technique described by Yao et al. using
      a vascular island flap based on a dorsal digital vessel, which allows transfer of
      the web proximally and retains the integrity of the web skin. The technique was
      used in nine patients, aged from 1 to 15 years at operation, with nine incomplete
      simple syndactylies. The results were assessed at a mean of 36 (range 5-60)
      months after surgery. No vascular compromise or web creep was noted. This
      technique enables transfer of web skin proximally in cases of simple, incomplete
      syndactyly, avoids the presence of scars in the web space and does not require
      skin grafts.

PMID- 19091738
TI  - Ewing's sarcoma of the hand.
AB  - A retrospective case review was carried out to report the outcomes in a
      contemporary case series of Ewing's sarcoma originating in the hand. We
      identified five patients treated since 1995. All five had wide surgical excision,
      one by ray amputation. All were treated with chemotherapy. Four patients also
      received radiation therapy, two to treat metastases and two as an adjunct to
      local excision. There were no local recurrences. Two patients developed
      metastases. Both died of their disease. Neither of these two patients had
      received local postoperative radiation therapy; one did not receive chemotherapy
      before definitive surgery. The other three patients were alive and free of
      disease at last follow-up, 4 to 12 years after initial presentation.

PMID- 19091739
TI  - Cold hypersensitivity 6 to 10 years after replantation or revascularisation of
      fingers: consequences for work and leisure activities.
AB  - We investigated cold hypersensitivity and activity in 81 adults (male/female
      76/5), 6 to 10 years after finger replantation/revascularisation (mean age at
      injury 43 (SD 15) years). Questionnaires included the McCabe Cold Sensitivity
      Severity Scale, Potential Work-Exposure Scale and the Disabilities of the Arm,
      Shoulder and Hand (DASH) score. Eighty per cent of the respondents were cold
      hypersensitive; 20% were severely or extremely cold hypersensitive. Of the 74
      patients employed at injury, 7% had changed work and 4% were not working due to
      cold hypersensitivity. The median score for cold exposure at work at follow-up
      was 153 (scale 0-300). The correlation between cold sensitivity and DASH work was
      low. One-third of the respondents experienced limitations in their leisure
      activities because of cold complaints. Long-term cold sensitivity was mild or
      moderate for most patients. Many cold hypersensitive patients managed to continue
      to work even under cold conditions and cold hypersensitivity was a greater
      problem in leisure activities.

PMID- 19091740
TI  - Engineering of the cofactor specificities and isoform-specific inhibition of
      malic enzyme.
AB  - Malic enzyme (ME) is a family of enzymes that catalyze a reversible oxidative
      decarboxylation of l-malate to pyruvate with simultaneous reduction of NAD(P)(+)
      to NAD(P)H. According to the cofactor specificity, the mammalian enzyme can be
      categorized into three isoforms. The cytosolic (c) and mitochondrial (m) NADP(+)
      dependent MEs utilize NADP(+) as the cofactor. The mitochondrial NAD(P)(+)
      dependent ME can use either NAD(+) or NADP(+) as the cofactor. In addition, the m
      NAD(P)-ME isoform can be inhibited by ATP and allosterically activated by
      fumarate. In this study, we delineated the determinants for cofactor specificity
      and isoform-specific inhibition among the ME isoforms. Our data strongly suggest
      that residue 362 is the decisive factor determining cofactor preference. All the
      mutants containing Q362K (Q362K, K346S/Q362K, Y347K/Q362K, and K346S/Y347K/Q362K)
      have a larger k(cat,NADP) value compared with the k(cat,NAD) value, indicating
      that the enzyme has changed to use NADP(+) as the preferred cofactor.
      Furthermore, we suggest that Lys-346 in m-NAD(P)-ME is crucial for the isoform
      specific ATP inhibition. The enzymes containing the K346S mutation (K346S,
      K346S/Y347K, K346S/Q362K, and K346S/Y347K/Q362K) are much less inhibited by ATP
      and have a larger K(i,ATP) value. Kinetic analysis also suggests that residue 347
      functions in cofactor specificity. Here we demonstrate that the human
      K346S/Y347K/Q362K m-NAD(P)-ME has completely shifted its cofactor preference to
      become an NADP(+)-specific ME. In the triple mutant, Lys-362, Lys-347, and Ser
      346 work together and function synergistically to increase the binding affinity
      for NADP(+).

PMID- 19091741
TI  - Crystal structure of the N-terminal domain of anaphase-promoting complex subunit
      7.
AB  - Anaphase-promoting complex or cyclosome (APC/C) is an unusual E3 ubiquitin ligase
      and an essential protein that controls mitotic progression. APC/C includes at
      least 13 subunits, but no structure has been determined for any tetratricopeptide
      repeat (TPR)-containing subunit (Apc3 and -6-8) in the TPR subcomplex of APC/C.
      Apc7 is a TPR-containing subunit that exists only in vertebrate APC/C. Here we
      report the crystal structure of quad mutant of nApc7 (N-terminal fragment,
      residues 1-147) of human Apc7 at a resolution of 2.5 A. The structure of nApc7
      adopts a TPR-like motif and has a unique dimerization interface, although the
      protein does not contain the conserved TPR sequence. Based on the structure of
      nApc7, in addition to previous experimental findings, we proposed a putative
      homodimeric structure for full-length Apc7. This model suggests that TPR
      containing subunits self-associate and bind to adaptors and substrates via an IR
      peptide in TPR-containing subunits of APC/C.

PMID- 19091742
TI  - Thinking outside the box about Ras.

PMID- 19091743
TI  - Signaling threshold regulation by the Ras effector IMP.
AB  - The Ras effector and E3 ligase family member IMP (impedes mitogenic signal
      propagation) acts as a steady-state resistor within the Raf-MEK-ERK kinase
      module. IMP concentrations are directly regulated by Ras, through induction of
      autoubiquitination, to permit productive Raf-MEK complex assembly. Inhibition of
      Raf-MEK pathway activation by IMP occurs through the inactivation of KSR, a
      scaffold/adapter protein that couples activated Raf to its substrate MEK1. The
      capacity of IMP to inhibit signal propagation through Raf to MEK is, in part, a
      consequence of disrupting KSR1 homo-oligomerization and c-Raf-B-Raf hetero
      oligomerization. These observations suggest that IMP functions as a threshold
      modulator, controlling sensitivity of the cascade to stimulus by directly
      limiting the assembly of functional KSR1-dependent Raf-MEK complexes.

PMID- 19091744
TI  - Rassf family of tumor suppressor polypeptides.
AB  - The Rassf1-6 polypeptides each contain a Ras/Rap association domain, which
      enables binding to several GTP-charged Ras-like GTPases, at least in vitro or
      when overexpressed. The Ras/Rap association domains are followed by SARAH
      domains, which mediate Rassf heterodimerization with the Mst1/2 protein kinases.
      Rassf1A is unequivocally a tumor suppressor, and all Rassf proteins behave like
      tumor suppressors, exhibiting epigenetic silencing of expression in many human
      cancers and pro-apoptotic and/or anti-proliferative effects when re-expressed in
      tumor cell lines. Herein, we review the binding of the Rassf polypeptides to Ras
      like GTPases and the Mst1/2 kinases and their role in Rassf function.

PMID- 19091745
TI  - Specificity in Ras and Rap signaling.
AB  - Ras and Rap proteins are closely related small GTPases. Whereas Ras is known for
      its role in cell proliferation and survival, Rap1 is predominantly involved in
      cell adhesion and cell junction formation. Ras and Rap are regulated by different
      sets of guanine nucleotide exchange factors and GTPase-activating proteins,
      determining one level of specificity. In addition, although the effector domains
      are highly similar, Rap and Ras interact with largely different sets of
      effectors, providing a second level of specificity. In this review, we discuss
      the regulatory proteins and effectors of Ras and Rap, with a focus on those of
      Rap.

PMID- 19091747
TI  - Carbon monoxide-releasing antibacterial molecules target respiration and global
      transcriptional regulators.
AB  - Carbon monoxide, a classical respiratory inhibitor, also exerts vasodilatory,
      anti-inflammatory, and antiapoptotic effects. CO-releasing molecules have
      therapeutic value, increasing phagocytosis and reducing sepsis-induced lethality.
      Here we identify for the first time the bacterial targets of
      Ru(CO)(3)Cl(glycinate) (CORM-3), a ruthenium-based carbonyl that liberates CO
      rapidly under physiological conditions. Contrary to the expectation that CO would
      be preferentially inhibitory at low oxygen tensions or anaerobically, Escherichia
      coli cultures were also sensitive to CORM-3 at concentrations equimolar with
      oxygen. CORM-3, assayed as ruthenium, was taken up by bacteria and rapidly
      delivered CO intracellularly to terminal oxidases. Microarray analysis of CORM-3
      treated cells revealed extensively modified gene expression, notably down
      regulation of genes encoding key aerobic respiratory complexes. Genes involved in
      metal metabolism, homeostasis, or transport were also differentially expressed,
      and free intracellular zinc levels were elevated. Probabilistic modeling of
      transcriptomic data identified the global transcription regulators ArcA, CRP,
      Fis, FNR, Fur, BaeR, CpxR, and IHF as targets and potential CO sensors. Our
      discovery that CORM-3 is an effective inhibitor and global regulator of gene
      expression, especially under aerobic conditions, has important implications for
      administration of CO-releasing agents in sepsis and inflammation.

PMID- 19091746
TI  - The chaperones Hsp90 and Cdc37 mediate the maturation and stabilization of
      protein kinase C through a conserved PXXP motif in the C-terminal tail.
AB  - The life cycle of protein kinase C (PKC) is tightly controlled by mechanisms that
      mature the enzyme, sustain the activation-competent enzyme, and degrade the
      enzyme. Here we show that a conserved PXXP motif (Kannan, N., Haste, N., Taylor,
      S. S., and Neuwald, A. F. (2007) Proc. Natl. Acad. Sci. U. S. A. 104, 1272-1277),
      in the C-terminal tail of AGC (c-AMP-dependent protein kinase/protein kinase
      G/protein kinase C) kinases, controls the processing phosphorylation of
      conventional and novel PKC isozymes, a required step in the maturation of the
      enzyme into a signaling-competent species. Mutation of both Pro-616 and Pro-619
      to Ala in the conventional PKC betaII abolishes the phosphorylation and activity
      of the kinase. Co-immunoprecipitation studies reveal that conventional and novel,
      but not atypical, PKC isozymes bind the chaperones Hsp90 and Cdc37 through a PXXP
      dependent mechanism. Inhibitors of Hsp90 and Cdc37 significantly reduce the rate
      of processing phosphorylation of PKC. Of the two C-terminal sites processed by
      phosphorylation, the hydrophobic motif, but not the turn motif, is regulated by
      Hsp90. Overlay of purified Hsp90 onto a peptide array containing peptides
      covering the catalytic domain of PKC betaII identified regions surrounding the
      PXXP segment, but not the PXXP motif itself, as major binding determinants for
      Hsp90. These Hsp90-binding regions, however, are tethered to the C-terminal tail
      via a "molecular clamp" formed between the PXXP motif and a conserved Tyr (Tyr
      446) in the alphaE-helix. Disruption of the clamp by mutation of the Tyr to Ala
      recapitulates the phosphorylation defect of mutating the PXXP motif. These data
      are consistent with a model in which a molecular clamp created by the PXXP motif
      in the C-terminal tail and determinants in the alphaE-helix of the catalytic
      domain allows the chaperones Hsp90 and Cdc37 to bind newly synthesized PKC, a
      required event in the processing of PKC by phosphorylation.

PMID- 19091748
TI  - Slc2a5 (Glut5) is essential for the absorption of fructose in the intestine and
      generation of fructose-induced hypertension.
AB  - The identity of the transporter responsible for fructose absorption in the
      intestine in vivo and its potential role in fructose-induced hypertension remain
      speculative. Here we demonstrate that Glut5 (Slc2a5) deletion reduced fructose
      absorption by approximately 75% in the jejunum and decreased the concentration of
      serum fructose by approximately 90% relative to wild-type mice on increased
      dietary fructose. When fed a control (60% starch) diet, Glut5(-/-) mice had
      normal blood pressure and displayed normal weight gain. However, whereas
      Glut5(+/+) mice showed enhanced salt absorption in their jejuna in response to
      luminal fructose and developed systemic hypertension when fed a high fructose
      (60% fructose) diet for 14 weeks, Glut5(-/-) mice did not display fructose
      stimulated salt absorption in their jejuna, and they experienced a significant
      impairment of nutrient absorption in their intestine with accompanying
      hypotension as early as 3-5 days after the start of a high fructose diet.
      Examination of the intestinal tract of Glut5(-/-) mice fed a high fructose diet
      revealed massive dilatation of the caecum and colon, consistent with severe
      malabsorption, along with a unique adaptive up-regulation of ion transporters. In
      contrast to the malabsorption of fructose, Glut5(-/-) mice did not exhibit an
      absorption defect when fed a high glucose (60% glucose) diet. We conclude that
      Glut5 is essential for the absorption of fructose in the intestine and plays a
      fundamental role in the generation of fructose-induced hypertension. Deletion of
      Glut5 results in a serious nutrient-absorptive defect and volume depletion only
      when the animals are fed a high fructose diet and is associated with compensatory
      adaptive up-regulation of ion-absorbing transporters in the colon.

PMID- 19091750
TI  - pH Dependence of the photoactive yellow protein photocycle recovery reaction
      reveals a new late photocycle intermediate with a deprotonated chromophore.
AB  - The recovery reaction of the signaling state of photoactive yellow protein
      includes the following: (i) deprotonation of the p-coumaryl chromophore, (ii)
      refolding of the protein, and (iii) chromophore re-isomerization from the cis to
      the trans configuration. Through analysis of the pH dependence of this recovery
      reaction, we were able to provide proof for the existence of an additional
      photocycle intermediate. The spectral similarity between this new intermediate
      and the dark state indicates that the new intermediate has a deprotonated
      chromophore, which may facilitate chromophore re-isomerization. This spectral
      similarity also explains why this new intermediate has not been noticed in
      earlier studies. For our data analysis we introduce a photocycle model that takes
      into account the effect of the specific light regime selected, a model that was
      also used for simulations.

PMID- 19091749
TI  - Methylalpinumisoflavone inhibits hypoxia-inducible factor-1 (HIF-1) activation by
      simultaneously targeting multiple pathways.
AB  - Hypoxia is a common feature of solid tumors, and the extent of tumor hypoxia
      correlates with advanced disease stages and treatment resistance. The
      transcription factor hypoxia-inducible factor-1 (HIF-1) represents an important
      tumor-selective molecular target for anticancer drug discovery directed at tumor
      hypoxia. A natural product chemistry-based approach was employed to discover
      small molecule inhibitors of HIF-1. Bioassay-guided isolation of an active lipid
      extract of the tropical legumaceous plant Lonchocarpus glabrescens and structure
      elucidation afforded two new HIF-1 inhibitors: alpinumisoflavone (compound 1) and
      4'-O-methylalpinumisoflavone (compound 2). In human breast tumor T47D cells,
      compounds 1 and 2 inhibited hypoxia-induced HIF-1 activation with IC(50) values
      of 5 and 0.6 mum, respectively. At the concentrations that in hibited HIF-1
      activation, compound 2 inhibited hypoxic induction of HIF-1 target genes (CDKN1A,
      GLUT-1, and VEGF), tumor angiogenesis in vitro, cell migration, and chemotaxis.
      Compound 2 inhibits HIF-1 activation by blocking the induction of nuclear HIF
      1alpha protein, the oxygen-regulated subunit that controls HIF-1 activity.
      Mechanistic studies indicate that, unlike rotenone and other mitochondrial
      inhibitors, compound 2 represents the first small molecule that inhibits HIF-1
      activation by simultaneously suppressing mitochondrial respiration and disrupting
      protein translation in vitro. This unique mechanism distinguishes compound 2 from
      other small molecule HIF-1 inhibitors that are simple mitochondrial inhibitors or
      flavanoid-based protein kinase inhibitors.

PMID- 19091753
TI  - Mild stimulation for in vitro fertilization: making progress downward.

PMID- 19091752
TI  - Expression of amyotrophic lateral sclerosis-linked SOD1 mutant increases the
      neurotoxic potential of microglia via TLR2.
AB  - Amyotrophic lateral sclerosis (ALS) is a progressive motor neuron disease, in
      which activated microglia overexpressing ALS-linked SOD1 mutants (mSOD1) are
      known to contribute to neuronal death. However, it is unclear how mSOD1
      expression affects micoglial activation and subsequently damages neurons. In this
      study, we created mSOD1-overexpressing BV-2 microglial cell lines. Following
      TLR2, but not TLR4 stimulation, we observed that overexpression of human SOD1
      G93A, L8Q, or G10V mutant, as compared with the wild-type SOD1 or a mock control,
      significantly enhanced microglial secretion of a neurotoxic cytokine, tumor
      necrosis factor-alpha (TNF-alpha), which was dependent on the NADPH-oxidase
      mediated increased generation of reactive oxygen species (ROS). In further
      experiments, we demonstrated that mSOD1 expression regulated TNF-alpha secretion
      at a post-transcriptional level and involved ROS-sensitive TNF-alpha-converting
      enzymes, e.g. ADAM10 and -17, which shed TNF-alpha from its membrane-anchored
      precursor. Together with a recent report that the function of SOD1, as a self
      regulating redox sensor in NADPH oxidase-dependent ROS production, is lost due to
      its genetic mutations, we conclude that mSOD1 expression in ALS facilitates
      microglial neurotoxic inflammatory responses via TLR2, which is mediated by an
      uncontrolled ROS generation. The link, between mSOD1, innate immunity and NADPH
      oxidase, offers new opportunities in ALS therapies.

PMID- 19091751
TI  - Nonsense codons trigger an RNA partitioning shift.
AB  - T-cell receptor-beta (TCRbeta) genes naturally acquire premature termination
      codons (PTCs) as a result of programmed gene rearrangements. PTC-bearing TCRbeta
      transcripts are dramatically down-regulated to protect T-cells from the
      deleterious effects of the truncated proteins that would otherwise be produced.
      Here we provide evidence that two responses collaborate to elicit this dramatic
      down-regulation. One is rapid mRNA decay triggered by the nonsense-mediated decay
      (NMD) RNA surveillance pathway. We demonstrate that this occurs in highly
      purified nuclei lacking detectable levels of three different cytoplasmic markers,
      but containing an outer nuclear membrane marker, suggesting that decay occurs
      either in the nucleoplasm or at the outer nuclear membrane. The second response
      is a dramatic partitioning shift in the nuclear fraction-to-cytoplasmic fraction
      mRNA ratio that results in few TCRbeta transcripts escaping to the cytoplasmic
      fraction of cells. Analysis of TCRbeta mRNA kinetics after either transcriptional
      repression or induction suggested that this nonsense codon-induced partitioning
      shift (NIPS) response is not the result of cytoplasmic NMD but instead reflects
      retention of PTC(+) TCRbeta mRNA in the nuclear fraction of cells. We identified
      TCRbeta sequences crucial for NIPS but found that NIPS is not exclusively a
      property of TCRbeta transcripts, and we identified non-TCRbeta sequences that
      elicit NIPS. RNA interference experiments indicated that NIPS depends on the NMD
      factors UPF1 and eIF4AIII but not the NMD factor UPF3B. We propose that NIPS
      collaborates with NMD to retain and degrade a subset of PTC(+) transcripts at the
      outer nuclear membrane and/or within the nucleoplasm.

PMID- 19091754
TI  - The clinical significance of the retrieval of a low number of oocytes following
      mild ovarian stimulation for IVF: a meta-analysis.
AB  - BACKGROUND: Milder ovarian stimulation protocols for in vitro fertilization (IVF)
      are being developed to minimize adverse effects. Mild stimulation regimens result
      in a decreased number of oocytes at retrieval. After conventional ovarian
      stimulation for IVF, a low number of oocytes are believed to represent poor
      ovarian reserve resulting in reduced success rates. Recent studies suggest that a
      similar response following mild stimulation is associated with better outcomes.
      METHODS: This review investigates whether the retrieval of a low number of
      oocytes following mild ovarian stimulation is associated with impaired
      implantation rates. Three randomized controlled trials comparing the efficacy of
      the mild ovarian stimulation regimen (involving midfollicular phase initiation of
      FSH and GnRH co-treatment) for IVF with a conventional long GnRH agonist co
      treatment stimulation protocol could be identified by means of a systematic
      literature search. RESULTS: These studies comprised a total of 592 first
      treatment cycles. Individual patient data analysis showed that the mild
      stimulation protocol results in a significant reduction of retrieved oocytes
      compared with conventional ovarian stimulation (median 6 versus 9, respectively,
      P < 0.001). Optimal embryo implantation rates were observed with 5 oocytes
      retrieved following mild stimulation (31%) versus 10 oocytes following
      conventional stimulation (29%) (P = 0.045). CONCLUSIONS: The optimal number of
      retrieved oocytes depends on the ovarian stimulation regimen. After mild ovarian
      stimulation, a modest number of oocytes is associated with optimal implantation
      rates and does not reflect a poor ovarian response. Therefore, the fear of
      reducing the number of oocytes retrieved following mild ovarian stimulation
      appears to be unjustified.

PMID- 19091755
TI  - Mild ovarian stimulation for IVF.
AB  - BACKGROUND: Mild ovarian stimulation for in vitro fertilization (IVF) aims to
      achieve cost-effective, patient-friendly regimens which optimize the balance
      between outcomes and risks of treatment. METHODS: Pubmed and Medline were
      searched up to end of January 2008 for papers on ovarian stimulation protocols
      for IVF. Additionally, references to related studies were selected wherever
      possible. RESULTS: Studies show that mild interference with the decrease in
      follicle-stimulating hormone levels in the mid-follicular phase was sufficient to
      override the selection of a single dominant follicle. Gonadotrophin-releasing
      hormone antagonists compared with agonists reduce length and dosage of
      gonadotrophin treatment without a significant reduction in the probability of
      live birth (OR 0.86, 95% CI 0.72-1.02). Mild ovarian stimulation may be achieved
      with limited gonadotrophins or with alternatives such as anti-estrogens or
      aromatase inhibitors. Another option is luteinizing hormone or human chorionic
      gonadotrophin administration during the late follicular phase. Studies regarding
      these approaches are discussed individually; small sample size of single studies
      along with heterogeneity in patient inclusion criteria as well as outcomes
      analysed does not allow a meta-analysis to be performed. Additionally, the
      implications of mild ovarian stimulation for embryo quality, endometrial
      receptivity, cost and the psychological impact of IVF treatment are discussed.
      CONCLUSIONS: Evidence in favour of mild ovarian stimulation for IVF is
      accumulating in recent literature. However, further, sufficiently powered
      prospective studies applying novel mild treatment regimens are required and
      structured reporting of the incidence and severity of complications, the number
      of treatment days, medication used, cost, patient discomfort and number of
      patient drop-outs in studies on IVF is encouraged.

PMID- 19091756
TI  - Please, sir, I want some more.

PMID- 19091757
TI  - Rugby (the religion of Wales) and its influence on the Catholic church: should
      Pope Benedict XVI be worried?
AB  - OBJECTIVE: To explore the perceived wisdom that papal mortality is related to the
      success of the Welsh rugby union team. DESIGN: Retrospective observational study
      of historical Vatican and sporting data. MAIN OUTCOME MEASURE: Papal deaths
      between 1883 and the present day. RESULTS: There is no evidence of a link between
      papal deaths and any home nation grand slams (when one nation succeeds in beating
      all other competing teams in every match). There was, however, weak statistical
      evidence to support an association between Welsh performance and the number of
      papal deaths. CONCLUSION: Given the dominant Welsh performances of 2008, the
      Vatican medical team should take special care of the pontiff this Christmas.

PMID- 19091758
TI  - Festive medical myths.

PMID- 19091759
TI  - Appointments timed in proximity to annual milestones and compliance with
      screening: randomised controlled trial.
AB  - OBJECTIVE: To investigate whether appointments for screening timed in proximity
      to annual milestones (birthdays, Christmas and New Year) may be used as a
      strategy to improve attendance for screening for colorectal cancer. DESIGN:
      Randomised controlled trial. SETTING: City of Oslo (urban) and Telemark county
      (urban and rural), Norway. PARTICIPANTS: 12,960 screened adults (64.7% of those
      invited). MAIN OUTCOME MEASURE: Attendance rates for each week and month of
      assigned appointment. RESULTS: Attendance rates were significantly higher in
      December than the rest of the year (72.3% v 64.6%, P<0.001) in adults who
      received an invitation in the week of their birthday or were assigned to
      screening in the first or second week after their birthday (67.9% v 64.5%,
      P=0.007). This effect was most pronounced in the urban population of Oslo. In a
      multivariable logistic regression model, attendance improved in those who
      received an invitation in the week of their birthday or were assigned to
      screening in the first or second week after their birthday (odds ratio 1.15, 95%
      confidence interval 1.03 to 1.28) and those who were assigned to screening in
      December (odds ratio 1.45, 1.16 to 1.82). CONCLUSION: Attendance rates for
      screening for colorectal cancer were higher in December and around attendees'
      birthdays, the latter particularly in an urban population. Compliance with
      screening programmes may therefore be improved by timing invitations in proximity
      to annual milestones. TRIAL REGISTRATION: Clinical Trials NCT00119912.

PMID- 19091760
TI  - Frankincense: systematic review.
AB  - OBJECTIVE: To assess evidence from randomised clinical trials about the
      effectiveness of extracts of Boswellia serrata (frankincense). DESIGN: Systematic
      review. DATA SOURCES: Electronic searches on Medline, Embase, Cinahl, Amed, and
      Cochrane Library. Hand searches of conference proceedings, bibliographies, and
      departmental files. REVIEW METHODS: All randomised clinical trials of B serrata
      extract as a treatment for any human medical condition were included and studies
      of B serrata preparations combined with other ingredients were excluded. Titles
      and abstracts of all retrieved articles were read and hard copies of all relevant
      articles were obtained. Selection of studies, data extraction and validation were
      done by the author. The Jadad score was used to evaluate the methodological
      quality of all included trials. RESULTS: Of 47 potentially relevant studies,
      seven met all inclusion criteria (five placebo controlled, two with active
      controls). The included trials related to asthma, rheumatoid arthritis, Crohn's
      disease, osteoarthritis, and collagenous colitis. Results of all trials indicated
      that B serrata extracts were clinically effective. Three studies were of good
      methodological quality. No serious safety issues were noted. CONCLUSIONS: The
      evidence for the effectiveness of B serrata extracts is encouraging but not
      compelling.

PMID- 19091761
TI  - Head and neck injury risks in heavy metal: head bangers stuck between rock and a
      hard bass.
AB  - OBJECTIVE: To investigate the risks of mild traumatic brain injury and neck
      injury associated with head banging, a popular dance form accompanying heavy
      metal music. DESIGN: Observational studies, focus group, and biomechanical
      analysis. PARTICIPANTS: Head bangers. MAIN OUTCOME MEASURES: Head Injury
      Criterion and Neck Injury Criterion were derived for head banging styles and both
      popular heavy metal songs and easy listening music controls. RESULTS: An average
      head banging song has a tempo of about 146 beats per minute, which is predicted
      to cause mild head injury when the range of motion is greater than 75 degrees .
      At higher tempos and greater ranges of motion there is a risk of neck injury.
      CONCLUSION: To minimise the risk of head and neck injury, head bangers should
      decrease their range of head and neck motion, head bang to slower tempo songs by
      replacing heavy metal with adult oriented rock, only head bang to every second
      beat, or use personal protective equipment.

PMID- 19091762
TI  - Is golf bad for your hearing?

PMID- 19091763
TI  - Coca-Cola douches and contraception.

PMID- 19091764
TI  - Evaluating service delivery interventions to enhance patient safety.

PMID- 19091765
TI  - Improving workforce is crucial to viability of Europe's health services,
      commission says.

PMID- 19091766
TI  - European Commission urges governments to reduce hospital acquired infections.

PMID- 19091768
TI  - RIM-BP3 is a manchette-associated protein essential for spermiogenesis.
AB  - During spermiogenesis, round spermatids are converted into motile sperm in
      mammals. The mechanisms responsible for sperm morphogenesis are poorly
      understood. We have characterized a novel protein, RIM-BP3, with a specialized
      function in spermatid development in mice. The RIM-BP3 protein is associated with
      the manchette, a transient microtubular structure believed to be important for
      morphogenesis during spermiogenesis. Targeted deletion of the RIM-BP3 gene
      resulted in male infertility owing to abnormal sperm heads, which are
      characterized by a deformed nucleus and a detached acrosome. Consistent with its
      role in morphogenesis, the RIM-BP3 protein physically associates with Hook1, a
      known manchette-bound protein required for sperm head morphogenesis.
      Interestingly, RIM-BP3 does not interact with the truncated Hook1 protein
      characterized in azh (abnormal spermatozoon head) mutant mice. Moreover, RIM-BP3
      and Hook1 mutant mice display several common abnormalities, in particular with
      regard to the ectopic positioning of the manchette within the spermatid, a
      presumed cause of sperm head deformities. These observations suggest an essential
      role for RIM-BP3 in manchette development and function through its interaction
      with Hook1. As the occurrence of deformed spermatids is one of the common
      abnormalities leading to malfunctional sperm, identification of RIM-BP3 might
      provide insight into the molecular cue underlying causes of male infertility in
      humans.

PMID- 19091769
TI  - Prox1 maintains muscle structure and growth in the developing heart.
AB  - Impaired cardiac muscle growth and aberrant myocyte arrangement underlie
      congenital heart disease and cardiomyopathy. We show that cardiac-specific
      inactivation of the murine homeobox transcription factor Prox1 results in the
      disruption of expression and localisation of sarcomeric proteins, gross myofibril
      disarray and growth-retarded hearts. Furthermore, we demonstrate that Prox1 is
      required for direct transcriptional regulation of the genes encoding the
      structural proteins alpha-actinin, N-RAP and zyxin, which collectively function
      to maintain an actin-alpha-actinin interaction as the fundamental association of
      the sarcomere. Aspects of abnormal heart development and the manifestation of a
      subset of muscular-based disease have previously been attributed to mutations in
      key structural proteins. Our study reveals an essential requirement for direct
      transcriptional regulation of sarcomere integrity, in the context of enabling
      foetal cardiomyocyte hypertrophy, maintenance of contractile function and
      progression towards inherited or acquired myopathic disease.

PMID- 19091770
TI  - Flamingo regulates epiboly and convergence/extension movements through cell
      cohesive and signalling functions during zebrafish gastrulation.
AB  - During vertebrate gastrulation, the body axis is established by coordinated and
      directional movements of cells that include epiboly, involution, and convergence
      and extension (C&E). Recent work implicates a non-canonical Wnt/planar cell
      polarity (PCP) pathway in the regulation of C&E. The Drosophila atypical cadherin
      Flamingo (Fmi) and its vertebrate homologue Celsr, a 7-pass transmembrane protein
      with extracellular cadherin repeats, regulate several biological processes,
      including C&E, cochlear cell orientation, axonal pathfinding and neuronal
      migration. Fmi/Celsr can function together with molecules involved in PCP, such
      as Frizzled (Fz) and Dishevelled (Dsh), but there is also some evidence that it
      may act as a cell adhesion molecule in a PCP-pathway-independent manner. We show
      that abrogation of Celsr activity in zebrafish embryos results in epiboly defects
      that appear to be independent of the requirement for Celsr in PCP signalling
      during C&E. Using a C-terminal truncated form of Celsr that inhibits membrane
      presentation of wild-type Celsr through its putative pro-region, a hanging drop
      assay reveals that cells from embryos with compromised Celsr activity have
      different cohesive properties from wild-type cells. It is disruption of this
      ability of Celsr to affect cell cohesion that primarily leads to the in vivo
      epiboly defects. In addition, Lyn-Celsr, in which the intracellular domain of
      Celsr is fused to a membrane localisation signal (Lyn), inhibits Fz-Dsh complex
      formation during Wnt/PCP signalling without affecting epiboly. Fmi/Celsr
      therefore has a dual role in mediating two separate morphogenetic movements
      through its roles in mediating cell cohesion and Wnt/PCP signalling during
      zebrafish gastrulation.

PMID- 19091771
TI  - FastMap: fast eQTL mapping in homozygous populations.
AB  - MOTIVATION: Gene expression Quantitative Trait Locus (eQTL) mapping measures the
      association between transcript expression and genotype in order to find genomic
      locations likely to regulate transcript expression. The availability of both gene
      expression and high-density genotype data has improved our ability to perform
      eQTL mapping in inbred mouse and other homozygous populations. However, existing
      eQTL mapping software does not scale well when the number of transcripts and
      markers are on the order of 10(5) and 10(5)-10(6), respectively. RESULTS: We
      propose a new method, FastMap, for fast and efficient eQTL mapping in homozygous
      inbred populations with binary allele calls. FastMap exploits the discrete nature
      and structure of the measured single nucleotide polymorphisms (SNPs). In
      particular, SNPs are organized into a Hamming distance-based tree that minimizes
      the number of arithmetic operations required to calculate the association of a
      SNP by making use of the association of its parent SNP in the tree. FastMap's
      tree can be used to perform both single marker mapping and haplotype association
      mapping over an m-SNP window. These performance enhancements also permit
      permutation-based significance testing. AVAILABILITY: The FastMap program and
      source code are available at the website: http://cebc.unc.edu/fastmap86.html.

PMID- 19091772
TI  - Computational analysis of microRNA profiles and their target genes suggests
      significant involvement in breast cancer antiestrogen resistance.
AB  - MOTIVATION: Recent evidence shows significant involvement of microRNAs (miRNAs)
      in the initiation and progression of numerous cancers; however, the role of these
      in tumor drug resistance remains unknown. RESULTS: By comparing global miRNA and
      mRNA expression patterns, we examined the role of miRNAs in resistance to the
      'pure antiestrogen' fulvestrant, using fulvestrant-resistant MCF7-FR cells and
      their drug-sensitive parental estrogen receptor (ER)-positive MCF7 cells. We
      identified 14 miRNAs downregulated in MCF7-FR cells and then used both TargetScan
      and PITA to predict potential target genes. We found a negative correlation
      between expression of these miRNAs and their predicted target mRNA transcripts.
      In genes regulated by multiple miRNAs or having multiple miRNA-targeting sites,
      an even stronger negative correlation was found. Pathway analyses predicted these
      miRNAs to regulate specific cancer-associated signal cascades. These results
      suggest a significant role for miRNA-regulated gene expression in the onset of
      breast cancer antiestrogen resistance, and an improved understanding of this
      phenomenon could lead to better therapies for this often fatal condition.

PMID- 19091773
TI  - Precision and recall estimates for two-hybrid screens.
AB  - MOTIVATION: Yeast two-hybrid screens are an important method to map pairwise
      protein interactions. This method can generate spurious interactions (false
      discoveries), and true interactions can be missed (false negatives). Previously,
      we reported a capture-recapture estimator for bait-specific precision and recall.
      Here, we present an improved method that better accounts for heterogeneity in
      bait-specific error rates. RESULT: For yeast, worm and fly screens, we estimate
      the overall false discovery rates (FDRs) to be 9.9%, 13.2% and 17.0% and the
      false negative rates (FNRs) to be 51%, 42% and 28%. Bait-specific FDRs and the
      estimated protein degrees are then used to identify protein categories that yield
      more (or fewer) false positive interactions and more (or fewer) interaction
      partners. While membrane proteins have been suggested to have elevated FDRs, the
      current analysis suggests that intrinsic membrane proteins may actually have
      reduced FDRs. Hydrophobicity is positively correlated with decreased error rates
      and fewer interaction partners. These methods will be useful for future two
      hybrid screens, which could use ultra-high-throughput sequencing for deeper
      sampling of interacting bait-prey pairs. AVAILABILITY: All software (C source)
      and datasets are available as supplemental files and at http://www.baderzone.org
      under the Lesser GPL v. 3 license.

PMID- 19091774
TI  - Commentary: Maziak's essay, seen from another angle.

PMID- 19091775
TI  - Response: Time for species--course epidemiology?

PMID- 19091777
TI  - Commentary: Learning to be creative with HIV/AIDS studies: looking for the
      variation--not only the average.

PMID- 19091778
TI  - Multidisciplinary strategy for managing cardiovascular risks when treating
      patients with early breast cancer.
AB  - Adjuvant systemic therapies for the treatment of early-stage breast cancer (EBC)
      effectively treat the tumor and significantly decrease the risk for recurrence.
      However, some of these treatments are associated with an increased risk of
      cardiovascular adverse events. Cardiovascular complications related to cancer
      therapy may be a prominent concern in postmenopausal women with existing
      cardiovascular disease or in those who are at high risk for developing
      cardiovascular disease. The increased risk for cardiac toxicity in women
      receiving radiation, anthracyclines, and/or trastuzumab for the adjuvant
      treatment of EBC is well established. The risk of thromboembolic disease is
      higher in patients with estrogen receptor-positive EBC receiving tamoxifen in the
      adjuvant setting, whether it is given before or instead of an aromatase
      inhibitor. In addition, while available data suggest no substantial differences
      in the risk for ischemic cardiovascular events between aromatase inhibitors and
      tamoxifen, investigation is still ongoing. Based on this information, it is
      important for health care providers to understand the cardiovascular risks of
      treatment and how to monitor at-risk patients, particularly when multiple agents
      are used in combination or in succession. Improving cardiovascular outcomes in
      patients with EBC requires cardiovascular risk assessment, management, and long
      term follow-up care. Because of the multimodal treatment of EBC patients, their
      care requires a multidisciplinary approach to reduce not only the risk for breast
      cancer recurrence but also the risk for treatment-related cardiac toxicities.

PMID- 19091779
TI  - A public health approach to winning the war against cancer.
AB  - The "war on cancer" in the United States has been viewed primarily as an effort
      to develop and disseminate cancer cures, but cancer is far more easily prevented
      than cured. There are three major approaches to cancer prevention: Primary
      prevention, through reduction in risk factors and changes to the environment that
      reduce human exposure to widely-consumed cancer-promoting agents. The most
      important actions for primary prevention of cancer are those that reduce tobacco
      use through taxation, smoke-free environment policies, advertising restrictions,
      counter-advertising, and cessation programs. The World Health Organization's
      MPOWER package outlines these actions, each of which covered less than 5% of
      people in the world in 2007. Similarly, cancer can be prevented by reducing
      alcohol consumption through policies such as alcohol taxes and limits on alcohol
      sales, and restoring caloric balance through policies such as creating healthier
      food environments and engineering the built environment to increase opportunities
      for physical activity. Vaccination is an effective approach to preventing
      specific virus-associated cancers, such as using human papillomavirus vaccine to
      prevent cervical cancer and hepatitis B virus vaccine to prevent hepatocellular
      cancer. Secondary prevention reduces cancer mortality through screening and early
      treatment; this approach has been used successfully for breast and cervical
      cancer but is still underused against colon cancer. Progress can be made in all
      three approaches to cancer prevention, but will require a greater emphasis on
      public health programs and public policy. Winning the war on cancer will require
      a much larger investment in prevention to complement efforts to improve
      treatment.

PMID- 19091776
TI  - Point-counterpoint. The triumph of the null hypothesis: epidemiology in an age of
      change.
AB  - The recent confusion concerning the relation between hormone replacement therapy
      and cardiovascular disease has stirred a new wave of debate about the value and
      future of epidemiology. Opponents of epidemiology suggest an ever-diminishing
      role in an age of small risks and complex diseases, yet proponents are not in
      consensus about how to adapt their discipline to the challenges associated with
      ageing societies and changing disease patterns. While epidemiology is likely to
      be increasingly called upon to make sense of the risks involved with these
      changes, wading into this era with a mindset and tools that were derived from
      epidemiology's 'golden era' of tackling major risk factors, has created more
      confusion than understanding. Increasingly, we need to downsize epidemiology to
      what is testable, measurable, and relevant, based on robust methodology and
      public health rationale. Applying an evolutionary perspective, that views health
      problems of modernity as a manifestation of the mismatch between our ancient
      genes and hi-tech lifestyles, can provide guidance for a 21st century research
      agenda.

PMID- 19091781
TI  - Changes and predictive and prognostic value of the mitotic index, Ki-67, cyclin
      D1, and cyclo-oxygenase-2 in 710 operable breast cancer patients treated with
      neoadjuvant chemotherapy.
AB  - The current study expands upon previous work using a database of 710 patients
      treated with neoadjuvant chemotherapy. First, we studied phenotypic
      characteristics of tumors before and after chemotherapy using the following
      factors: the mitotic index of the Scarff-Bloom-Richardson grade, Ki-67, cyclin
      D1, and cyclo-oxygenase-2. Second, the predictive value of these factors on
      response was assessed. Third, we measured the prognostic impact of these markers
      post-therapy in comparison with clinical and pathological responses according to
      the Chevallier and Sataloff classifications. Patients were treated using
      different neoadjuvant chemotherapy combinations, mainly in successive prospective
      phase II trials. They received a median number of six cycles (range, 1-9). After
      neoadjuvant chemotherapy, patients underwent surgery and radiotherapy. In cases
      of important residual disease, some received additional courses of chemotherapy.
      In addition, menopausal patients with hormone receptor-positive tumors received
      tamoxifen for 5 years. According to our analysis, we found significant variations
      before and after neoadjuvant chemotherapy only for cyclin D1 and the mitotic
      index. Concerning the predictive value of biomarkers for response, Ki-67 and the
      mitotic index were predictive on univariate analysis, both for objective clinical
      and pathological complete responses. Because these two factors were correlated,
      no multivariate analyses were conducted. We then assessed the prognostic impact
      of the biopathological factors. When the factors were measured before
      chemotherapy, all were prognostic. When evaluated after chemotherapy, the mitotic
      index, objective clinical response, and pathological complete response were
      prognostic. Because these factors were correlated, no multivariate model was
      done. The main clinical fact is that there were significant correlations between
      clinical and pathological responses and variations in the biological factors
      studied.

PMID- 19091780
TI  - Carcinoid tumors.
AB  - Carcinoid tumors are rare, slow-growing neuroendocrine tumors arising from the
      enterochromaffin cells disseminated throughout the gastrointestinal and
      bronchopulmonary systems. Though they have been traditionally classified based on
      embryologic site of origin, morphologic pattern, and silver affinity, newer
      classification systems have been developed to emphasize the considerable clinical
      and histopathologic variability of carcinoid tumors found within each embryologic
      site of origin. These neoplasms pose a diagnostic challenge because they are
      often innocuous at the time of presentation, emphasizing the need for a
      multidisciplinary diagnostic approach using biochemical analysis, standard cross
      sectional imaging, and newer advances in nuclear medicine. Similarly, treatment
      of both primary and disseminated carcinoid disease reflects the need for a
      multidisciplinary approach, with surgery remaining the only curative modality.
      The prognosis for patients with these tumors is generally favorable; however, it
      can be quite variable and is related to the location of the primary tumor, extent
      of metastatic disease at initial presentation, and time of diagnosis.

PMID- 19091782
TI  - Byrsonima fagifolia Niedenzu Apolar Compounds with Antitubercular Activity.
AB  - Bioassay-guided fractionation of the chloroform extract of Byrsonima fagifolia
      leaves led to the isolation of active antitubercular compounds alkane
      dotriacontane (Minimal Inhibitory Concentration-MIC, 62.5 MUg mL(-1)),
      triterpenoids as bassic acid (MIC = 2.5 MUg mL(-1)), alpha-amyrin acetate (MIC =
      62.5 MUg mL(-1)), a mixture of lupeol, alpha- and beta-amyrin (MIC = 31.5 MUg mL(
      1)) and a mixture of lupeol, and acetates of alpha- and beta-amyrin (MIC = 31.5
      MUg mL(-1)). The antimycobacterial activity was determined by the Microplate
      Alamar Blue Assay (MABA) and the structures of promising compounds were
      determined by spectroscopic analysis. This investigation constitutes the first
      report of a chemical and antitubercular study of apolar compounds from B.
      fagifolia Niedenzu (IK).

PMID- 19091784
TI  - Obesity in adults in Turkey: age and regional effects.
AB  - BACKGROUND: In this study, the body mass index (BMI) of Turkish population is
      calculated using a sample of 4205 persons consisting of 2263 male and 1942 female
      individuals in 2007. The study contains data from all seven geographical regions
      (Aegean, Black Sea, Central Anatolia, Eastern Anatolia, Marmara, Mediterranean
      and Southeast Anatolia) of Turkey and from all age groups from 20 to 85 years.
      METHOD: In this study, height and weight data were measured and used for
      calculating the BMI of Turkish population accounting for age and regional
      effects. RESULTS: This study's analysis found that age, region and gender are
      significant determinants on obesity of Turkish population. Also, Turkish
      population has higher obesity prevalence than most of the European countries.
      Overall, it was found that 56% of Turkish Population is overweight while 41% is
      in the normal range. CONCLUSIONS: This is the first study related to obesity in
      Turkey covering all seven regions and all age groups. Analyzing the differences
      of obesity prevalence between genders, geographical regions and age groups will
      be beneficial for better understanding the reasons behind obesity in Turkey.

PMID- 19091783
TI  - Comparative glycoproteomics: approaches and applications.
AB  - Glycosylation plays fundamental roles in controlling various biological
      processes. Therefore, glycosylation analysis has become an important target for
      proteomic research and has great potential for clinical applications. With the
      continuous development and refinement of glycoprotein isolation methods,
      increasing attention has been directed to the quantitative and comparative
      aspects. This review describes the mass spectrometry (MS)-based techniques for
      the comparative analysis of glycoproteins and their applications to answer a wide
      range of interesting biological questions.

PMID- 19091785
TI  - Cyclosporine stimulates the renal epithelial sodium channel by elevating
      cholesterol.
AB  - Cyclosporine A (CsA) is an efficient immunosuppressant used for reducing
      allograft rejection but with a severe side effect of causing hypertension. We
      hypothesize that the renal epithelial sodium channel (ENaC) may participate in
      CsA-induced hypertension. In the present study, we used the patch-clamp cell
      attached configuration to examine whether and how CsA stimulates ENaC in A6
      distal nephron cells. The data showed that CsA significantly increased ENaC open
      probability. Since CsA is an inhibitor of the ATP-binding cassette A1 (ABCA1)
      transporter, we employed 4,4'-diisothiocyanatostilbene-2,2'-disulfonic acid
      (DIDS), another ABCA1 inhibitor, and found that DIDS mimicked the effects of CsA
      on ENaC basal and cholesterol-induced activity but without any additive effect if
      combined with CsA. CsA and DIDS also had an identical effect on reduced ENaC
      activity caused by cholesterol extraction. ABCA1 protein was detected in A6 cells
      by Western blot analysis. Confocal microscopy data showed that both CsA and DIDS
      facilitated A6 cells to uptake cholesterol. Since enhanced ENaC activity is known
      to cause hypertension, these data together suggest that CsA may cause
      hypertension by stimulating ENaC through a pathway associated with inhibition of
      ABCA1 and consequent elevation of cholesterol in the cells.

PMID- 19091786
TI  - Dual simulated childbirth injury delays anatomic recovery.
AB  - A dual childbirth injury model, including vaginal distension (VD) and pudendal
      nerve crush (PNC), may best represent the injuries seen clinically. The objective
      of this study was to investigate urethral function, anatomy, and neurotrophin
      expression after several simulated childbirth injuries. Groups of 140 rats
      underwent PNC, VD, PNC+VD, or neither (C). Four days after injury, all injury
      groups had significantly decreased leak-point pressure (LPP) compared with C
      rats. Ten days after injury, LPP in PNC and PNC+VD rats remained significantly
      lower than C rats. Three weeks after injury, LPP in all injury groups had
      recovered to C values. Histological evidence of injury was still evident in the
      external urethral sphincter (EUS) after VD and PNC+VD 10 days after injury. Three
      weeks after injury, the EUS of PNC+VD rats remained disrupted. One day after VD,
      brain-derived neurotrophic factor (BDNF) expression in the EUS was reduced, while
      neurotrophin-4 (NT-4) and nerve growth factor (NGF) expression was unchanged.
      BDNF, NT-4, and NGF expression was dramatically upregulated in the EUS after PNC.
      After PNC+VD, NGF expression was upregulated, and BDNF and NT-4 expression was
      upregulated somewhat but not to the same extent as after PNC. Ten days after
      injury, PNC+VD had the least number of normal nerve fascicles near the EUS,
      followed by PNC and VD. Twenty-one days after injury, all injury groups had fewer
      normal nerve fascicles, but without significant differences compared with C rats.
      PNC+VD therefore provides a more severe injury than PNC or VD alone.

PMID- 19091787
TI  - MnTMPyP, a cell-permeant SOD mimetic, reduces oxidative stress and apoptosis
      following renal ischemia-reperfusion.
AB  - Oxidative stress and apoptosis are important factors in the etiology of renal
      ischemia-reperfusion (I/R) injury. The present study tested the hypothesis that
      the cell-permeant SOD mimetic manganese(III) tetrakis(1-methyl-4
      pyridyl)porphyrin (MnTMPyP) protects the kidney from I/R-mediated oxidative
      stress and apoptosis in vivo. Male Sprague-Dawley rats (175-220 g) underwent
      renal I/R by bilateral clamping of the renal arteries for 45 min followed by
      reperfusion for 24 h. To examine the role of reactive oxygen species (ROS) in
      renal I/R injury, a subset of animals were treated with either saline vehicle
      (I/R Veh) or MnTMPyP (I/R Mn) (5 mg/kg ip) 30 min before and 6 h after surgery.
      MnTMPyP significantly attenuated the I/R-mediated increase in serum creatinine
      levels and decreased tubular epithelial cell damage following I/R. MnTMPyP also
      decreased TNF-alpha levels, gp(91phox), and lipid peroxidation after I/R.
      Furthermore, MnTMPyP inhibited the I/R-mediated increase in apoptosis and caspase
      3 activation. Interestingly, although MnTMPyP did not increase expression of the
      antiapoptotic protein Bcl-2, it decreased the expression of the proapoptotic
      genes Bax and FasL. These results suggest that MnTMPyP is effective in reducing
      apoptosis associated with renal I/R injury and that multiple signaling mechanisms
      are involved in ROS-mediated cell death following renal I/R injury.

PMID- 19091788
TI  - C-peptide reverses TGF-beta1-induced changes in renal proximal tubular cells:
      implications for treatment of diabetic nephropathy.
AB  - The crucial pathology underlying progressive chronic kidney disease in diabetes
      is tubulointerstitial fibrosis. Central to this process is epithelial-mesenchymal
      transformation (EMT) of proximal tubular epithelial cells driven by maladaptive
      transforming growth factor-beta1 (TGF-beta1) signaling. Novel signaling roles for
      C-peptide have recently been discovered with evidence emerging that C-peptide may
      mitigate microvascular complications of diabetes. We studied the potential for C
      peptide to interrupt injurious TGF-beta1 signaling pathways and thus block
      development of EMT in HK2 human kidney proximal tubular cells. Cells were
      incubated with TGF-beta1 either alone or with C-peptide in low or high glucose.
      Changes in cell morphology, TGF-beta1 receptor expression, vimentin, E-cadherin,
      and phosphorylated Smads were assessed. Luciferase reporters were used to assess
      Smad activity. The cytoskeleton was visualized by TRITC-phalloidin staining. The
      typical TGF-beta1-stimulated, EMT-associated morphological alterations of
      proximal tubular cells, including increased vimentin expression, decreased E
      cadherin expression, and cytoskeletal rearrangements, were prevented by C-peptide
      treatment. C-peptide also blocked TGF-beta1-induced upregulation of expression of
      both type I and type II TGF-beta1 receptors and attenuated TGF-beta1-mediated
      Smad phosphorylation and Smad transcriptional activity. These effects of C
      peptide were inhibited by pertussis toxin. The results demonstrate that C-peptide
      almost completely reversed the morphological changes in PT cells induced by TGF
      beta1 and suggest a role or C-peptide as a renoprotective agent in diabetic
      nephropathy.

PMID- 19091789
TI  - Direct upregulation of parathyroid calcium-sensing receptor and vitamin D
      receptor by calcimimetics in uremic rats.
AB  - To investigate whether the effect of the calcimimetic AMG 641 and calcitriol on
      CaSR and VDR expression could be separated from their ability to reduce
      parathyroid cell proliferation, five-sixth nephrectomized (5/6 Nx) rats received
      vehicle, AMG 641, calcitriol, or AMG 641+calcitriol either daily for 13 days
      (long-term protocol) or in a single dose (short-term protocol). In the long-term
      protocol, AMG 641, calcitriol, and their combination significantly reduced the
      percentage of proliferating parathyroid cells. Proliferation was uncontrolled in
      the short-term protocol. A significant increase in CaSR mRNA (% vs. beta-actin)
      was detected in rats treated with both calcitriol (1.60 +/- 0.30) and AMG 641
      (1.66 +/- 0.25) for 13 days (P = 0.01 vs. 5/6 Nx+vehicle, 0.89 +/- 0.09); and
      there was a further increase when both drugs were administered simultaneously
      (2.46 +/- 0.33). In the short-term protocol, only rats receiving AMG 641 alone
      (2.01 +/- 0.33, P < 0.001) showed increased expression of CaSR mRNA, whereas the
      combination (1.81 +/- 0.20) produced no additional benefit. AMG 641 also
      increased CaSR mRNA expression in vitro. Changes in VDR mRNA paralleled those of
      CaSR mRNA. In the long-term treatment, both AMG 641 (0.87 +/- 0.14) and
      calcitriol (0.99 +/- 0.12) increased VDR mRNA (P < 0.05 vs. 5/6 Nx+vehicle, 0.49
      +/- 0.10), and the increase was more accentuated when the drugs were combined
      (1.49 +/- 0.45). In the short-term protocol, only treatment with AMG 641, alone
      (1.52 +/- 0.41) or combined with calcitriol (1.86 +/- 0.24), increased VDR mRNA.
      In conclusion, our results demonstrate an acute increase in CaSR mRNA and VDR
      mRNA in the parathyroid glands of uremic rats treated with AMG 641, in which cell
      proliferation was uncontrolled, thus supporting a direct effect of calcimimetics
      on CaSR and VDR expression by hyperplastic parathyroid cells.

PMID- 19091790
TI  - Role of CuZn superoxide dismutase on carotid body function in heart failure
      rabbits.
AB  - AIMS: Peripheral chemoreflex sensitivity is potentiated in both clinical and
      experimental chronic heart failure (CHF). NADPH oxidase-derived superoxide
      mediates angiotensin II (Ang II)-enhanced carotid body (CB) chemoreceptor
      sensitivity in CHF rabbits, and tempol, the superoxide dismutase (SOD) mimetic,
      inhibits this Ang II- and CHF-enhanced superoxide anion effect. Here we
      investigated the role of cytoplasmic SOD [CuZn superoxide dismutase (CuZnSOD)] in
      the CB on chemoreceptor activity and function in CHF rabbits. METHODS AND
      RESULTS: CuZnSOD protein expression was decreased in CBs from CHF rabbits vs.
      sham (P < 0.05). Adenoviral CuZnSOD (Ad CuZnSOD) gene transfer to the CBs
      increased CuZnSOD protein expression and significantly reduced the baseline renal
      sympathetic nerve activity (RSNA) and the response of RSNA to hypoxia in the CHF
      rabbits (P < 0.05). Single-fibre discharge from CB chemoafferents during normoxia
      (baseline, at approximately 100 mmHg PO2) and in response to hypoxia were
      enhanced in CHF vs. sham rabbits (P < 0.05). Ad CuZnSOD decreased the baseline
      discharge (7.6 +/- 1.3 vs. 12.6 +/- 1.7 imp/s at approximately 100 mmHg PO2) and
      the response to hypoxia (22.4 +/- 1.6 vs. 32.3 +/- 1.2 imp/s at approximately 40
      mmHg PO2, P < 0.05) in CHF rabbits. Ad CuZnSOD also normalized the blunted
      outward K+ current (IK) in CB glomus cells from CHF rabbits (369 +/- 14 vs. 565
      +/- 31 pA/pF at +70 mV, P < 0.05). In addition, Ad CuZnSOD reduced the elevation
      of superoxide level in CBs from CHF rabbits. CONCLUSION: Downregulation of
      CuZnSOD in the CB contributes to the enhanced activity of CB chemoreceptors and
      chemoreflex function in CHF rabbits.

PMID- 19091792
TI  - Migration of inferior vena cava stent into right ventricle: two- and three
      dimensional echocardiographic imaging.
AB  - Right ventricular migration of a systemic venous stent is a rare complication. We
      present a case of stent migration in a 65-year-old male who underwent palliative
      intervention for inferior vena cava compression secondary to malignant
      mesothelioma. Two- and three-dimensional echocardiographic images revealed
      evidence of a free-stent trapped in the tricuspid valvular apparatus causing
      severe tricuspid regurgitation.

PMID- 19091791
TI  - Ets-1 mediates platelet-derived growth factor-BB-induced thrombomodulin
      expression in human vascular smooth muscle cells.
AB  - AIMS: Thrombomodulin (TM), a potent anticoagulant, is not detected in quiescent
      vascular smooth muscle cells (VSMCs). In diseased vessels, VSMC expresses TM, but
      the mechanisms are unclear. This study examined molecular mechanisms for TM
      expression in VSMCs. METHODS AND RESULTS: Platelet-derived growth factor-BB (PDGF
      BB) induced TM expression in cultured human aortic VSMCs. PDGF-induced TM is
      functional in activating protein C. TM induction was eliminated by inhibitors of
      Src kinase, phosphatidylinositol 3-kinase (PI3-kinase), and mammalian target of
      rapamycin (mTOR) and by expressing dominant-negative Akt while expressing active
      Akt-stimulated TM expression. PDGF-BB activated the TM promoter, and the deletion
      of a sequence segment -394/-255 drastically reduced TM promoter activity.
      Transcription factor E26 transformation-specific sequence-1 (Ets-1) was
      upregulated by PDGF-BB in a PI3-kinase- and mTOR-dependent manner. RNA
      interference of Ets-1 inhibited PDGF induction of TM, and overexpressing Ets-1
      increased TM expression. Chromatin immunoprecipitation and electrophoretic
      mobility shift assay detected increased Ets-1 binding to the TM promoter after
      PDGF treatment. Following carotid artery ligation of C57/BL6 mice, PDGF-BB and TM
      were co-expressed in the media and neointima. CONCLUSION: In VSMCs, PDGF-BB
      stimulates TM expression that is mainly mediated by Ets-1 via the Src kinase/PI3
      kinase/Akt/mTOR signalling pathway. Furthermore, PDGF-BB may regulate TM
      expression in VSMCs during vascular remodelling.

PMID- 19091793
TI  - Left ventricular non-compaction in identical twins with thalassaemia and cardiac
      iron overload.
AB  - Cardiac disease in patients with transfusion-dependent beta-thalassaemia major is
      well described. Cardiac manifestations may include left ventricular wall
      thickening and both systolic and diastolic dysfunctions. We describe a group of
      family members, including a pair of identical twins, each of whom suffered from
      thalassaemia major requiring multiple transfusions. Cardiac magnetic resonance
      demonstrated myocardial iron overload, and impairment of systolic function.
      Echocardiography confirmed both significant left ventricular systolic and
      diastolic impairment, along with features consistent with left ventricular non
      compaction. This finding has not been noted in association with thalassaemia
      related cardiac disease before. We then review the cardiac manifestations which
      occur in association with thalassaemia major.

PMID- 19091794
TI  - Contrast echocardiography for pulmonary arteriovenous malformations screening:
      does any bubble matter?
AB  - AIMS: To evaluate diagnostic accuracy of contrast echocardiography (CE) as
      compared with CT, for the screening of pulmonary arteriovenous malformations
      (PAVMs) in hereditary haemorrhagic telangiectasia (HHT); to evaluate the clinical
      significance of semi-quantitative analysis of a shunt on CE. METHODS AND RESULTS:
      A blinded prospective study was conducted in 190 consecutive subjects at risk of
      HHT who underwent screening for PAVMs, including clinical evaluation, pulse
      oximetry, standard and CE, and chest multirow CT without contrast medium. A semi
      quantitative analysis of the shunt size was performed according to the contrast
      echo opacification of the left-sided chambers: Grade 0, no bubbles; 1, occasional
      filling with <20 bubbles; 2, moderate filling; 3, complete opacification. The
      first 100 patients were compared with 100 controls. A total of 119 (63%) patients
      had positive CE (32.2% Grade 1, 13.1% Grade 2, 11% Grade 3, 6.3% with patent
      foramen ovale). The overall diagnostic performance of CE was sensitivity 1.00,
      specificity 0.49, positive predictive value (PPV) 0.32, negative predictive value
      (NPV) 1.00. The PPV for the different grades was 0.00 for Grade 1, 0.56 for Grade
      2, 1.00 for Grade 3; the NPV of Grade 0 was 1.00. A significant correlation was
      found between the CE grading and the number of PAVM, and complications (P <
      0.0001). CONCLUSION: CE is an extremely sensitive procedure for the detection of
      PAVMs with substantial clinical impact.

PMID- 19091795
TI  - Association of functionally significant Melanocortin-4 but not Melanocortin-3
      receptor mutations with severe adult obesity in a large North American case
      control study.
AB  - Functionally significant heterozygous mutations in the Melanocortin-4 receptor
      (MC4R) have been implicated in 2.5% of early onset obesity cases in European
      cohorts. The role of mutations in this gene in severely obese adults,
      particularly in smaller North American patient cohorts, has been less convincing.
      More recently, it has been proposed that mutations in a phylogenetically and
      physiologically related receptor, the Melanocortin-3 receptor (MC3R), could also
      be a cause of severe human obesity. The objectives of this study were to
      determine if mutations impairing the function of MC4R or MC3R were associated
      with severe obesity in North American adults. We studied MC4R and MC3R mutations
      detected in a total of 1821 adults (889 severely obese and 932 lean controls)
      from two cohorts. We systematically and comparatively evaluated the functional
      consequences of all mutations found in both MC4R and MC3R. The total prevalence
      of rare MC4R variants in severely obese North American adults was 2.25% (CI(95%):
      1.44-3.47) compared with 0.64% (CI(95%): 0.26-1.43) in lean controls (P < 0.005).
      After classification of functional consequence, the prevalence of MC4R mutations
      with functional alterations was significantly greater when compared with controls
      (P < 0.005). In contrast, the prevalence of rare MC3R variants was not
      significantly increased in severely obese adults [0.67% (CI(95%): 0.27-1.50)
      versus 0.32% (CI(95%): 0.06-0.99)] (P = 0.332). Our results confirm that
      mutations in MC4R are a significant cause of severe obesity, extending this
      finding to North American adults. However, our data suggest that MC3R mutations
      are not associated with severe obesity in this population.

PMID- 19091796
TI  - Markers of innate immune function are associated with vitamin a stores in men.
AB  - Recommendations for vitamin A intake and liver stores are based on maintaining
      normal vision. We propose that higher levels may be required to maintain normal
      innate immune function. To test this hypothesis, we conducted an 8-wk residential
      study among 36 healthy Bangladeshi men with low vitamin A stores. Subjects were
      randomized to receive vitamin A (240 mg in 4 doses) or placebo during study wk 2
      and 3. They received 2 vaccines during wk 5 and vitamin A stores were estimated
      by isotopic dilution at wk 8. The serum concentration of the chemokine interferon
      gamma-induced protein 10, a component of T-helper 1 (Th1) response, increased
      significantly after supplementation and was positively and significantly
      associated with vitamin A stores. Blood concentrations of natural killer (NK) and
      NK T-cells, which have anticancer and antiviral activity, were positively
      associated with stores (P < 0.05), as was monocyte oxidative burst (P < 0.05), a
      marker of bacterial killing ability. However, serum interleukin (IL)-6 and IL-17,
      cytokines that regulate the antibacterial Th17 response, were significantly and
      negatively associated with stores, as was production of the regulatory cytokine
      IL-10 by whole-blood cultures stimulated with bacterial lipopolysaccharide. In
      summary, vitamin A stores were positively associated with several measures of
      innate immune activity across a broad range of stores, suggesting that vitamin A
      enhances protection against diverse pathogens even at concentrations above those
      needed to maintain normal vision. The negative association of stores with serum
      IL-6 and IL-17 suggests that not all protective responses are similarly enhanced
      by vitamin A.

PMID- 19091797
TI  - Height for age increased while body mass index for age remained stable between
      1968 and 2007 among Guatemalan children.
AB  - Promotion of optimal growth while preventing the emergence of obesity in
      childhood requires an understanding of the dynamics over time of linear growth
      and weight for height. To assess long-term secular trends in height-for-age and
      BMI for age in children <6 y old, we analyzed a series of cross-sectional surveys
      conducted between 1968 and 2007 in 4 villages in eastern Guatemala. We used
      height and weight of children <6 y old (n = 507, 606, 627, 704, 526, and 502 for
      survey years 1968, 1972, 1977, 1988, 1997, and 2005-7, respectively) to compute
      height-for-age Z-score (HAZ) and BMI-for-age Z-score (BMIZ) based on WHO growth
      standards. HAZ was -2.73 +/- 1.12 (mean +/- SD) in 1968 and -1.16 +/- 1.16 in
      2005-7 (P < 0.001). The prevalence of stunting (HAZ <-2.0) was 73.0% in 1968 and
      23.1% in 2005-7 (P < 0.001). Among children 57-63 mo old, HAZ in 2005-7 was 1.20
      (95% CI, 0.79, 1.62) SD units higher than in 1968, corresponding to 5.6 cm in
      boys and 5.7 cm in girls. For all survey years except 2007, BMIZ increased
      through age 36 mo, then declined; for the 2005-7 sample, BMIZ did not vary by
      age. The prevalence of BMIZ >1.00 was 21.1% in 1968 and 19.6% in 2005-7 (P >
      0.05); for BMI <-1.00, the respective prevalences were 7.9% and 5.2% (P > 0.05).
      There have been long-term improvements in child growth, as measured by HAZ,
      without concurrent increases in BMI over successive generations of children.

PMID- 19091798
TI  - Continuous dose-response relationship of the LDL-cholesterol-lowering effect of
      phytosterol intake.
AB  - Phytosterols (plant sterols and stanols) are well known for their LDL-cholesterol
      (LDL-C)-lowering effect. A meta-analysis of randomized controlled trials in
      adults was performed to establish a continuous dose-response relationship that
      would allow predicting the LDL-C-lowering efficacy of different phytosterol
      doses. Eighty-four trials including 141 trial arms were included. A nonlinear
      equation comprising 2 parameters (the maximal LDL-C lowering and an incremental
      dose step) was used to describe the dose-response curve. The overall pooled
      absolute (mmol/L) and relative (%) LDL-C-lowering effects of phytosterols were
      also assessed with a random effects model. The pooled LDL-C reduction was 0.34
      mmol/L (95% CI: -0.36, -0.31) or 8.8% (95% CI: -9.4, -8.3) for a mean daily dose
      of 2.15 g phytosterols. The impacts of subject baseline characteristics, food
      formats, type of phytosterols, and study quality on the continuous dose-response
      curve were determined by regression or subgroup analyses. Higher baseline LDL-C
      concentrations resulted in greater absolute LDL-C reductions. No significant
      differences were found between dose-response curves established for plant sterols
      vs. stanols, fat-based vs. non fat-based food formats and dairy vs. nondairy
      foods. A larger effect was observed with solid foods than with liquid foods only
      at high phytosterol doses (>2 g/d). There was a strong tendency (P = 0.054)
      towards a slightly lower efficacy of single vs. multiple daily intakes of
      phytosterols. In conclusion, the dose-dependent LDL-C-lowering efficacy of
      phytosterols incorporated in various food formats was confirmed and equations of
      the continuous relationship were established to predict the effect of a given
      phytosterol dose. Further investigations are warranted to investigate the impact
      of solid vs. liquid food formats and frequency of intake on phytosterol efficacy.

PMID- 19091799
TI  - Major patterns of dietary intake in adolescents and their stability over time.
AB  - A diet-patterns approach has often been used to describe eating patterns in
      adults but has rarely been used in adolescents. We used principal components
      factor analysis to: 1) describe the dietary patterns of a cohort of ethnically
      diverse youth during early and middle adolescence; 2) examine if the patterns
      persisted 5 y later; and 3) study secular trends. Project EAT-I (Time 1)
      collected data on 4746 middle school (younger cohort) and high school (older
      cohort) students in 31 Minnesota schools in 1998-1999. Project EAT-II (Time 2)
      resurveyed 53% (n = 2516) of the original cohort in 2003-2004. Dietary intake was
      assessed at Time 1 and 2 using the Youth/Adolescent FFQ. We identified dietary
      patterns separately by cohort (older/younger) and gender (boys/girls). At Time 1,
      we identified 4 patterns in early and middle adolescents that were relatively
      consistent between boys and girls that we labeled vegetable, fruit, sweet/salty
      snack food, and starchy food. Longitudinal analyses indicated that patterns were
      relatively stable over 5 y, with the exception of a new fast food pattern.
      Examination of age-matched secular trends in middle adolescents (older cohort at
      Time 1, younger cohort at Time 2) showed similar patterns, with the exception of
      the fast food pattern that emerged at Time 2 among middle adolescent boys. We
      identified dietary patterns in this adolescent population that differed from
      those usually found in adults. Patterns were similar across gender and age
      cohorts and were relatively similar over time, with the exception a new fast food
      pattern.

PMID- 19091800
TI  - Maternal fish oil supplementation during lactation may adversely affect long-term
      blood pressure, energy intake, and physical activity of 7-year-old boys.
AB  - Early nutrition may program obesity and cardiovascular risk later in life, and
      one of the potential agents is (n-3) long-chain PUFA (LCPUFA). In this study, our
      objective was to examine whether fish oil (FO) supplementation during lactation
      affects blood pressure and body composition of children. Danish mothers (n = 122)
      were randomized to FO [1.5 g/d (n-3) LCPUFA] or olive oil (OO) supplementations
      during the first 4 mo of lactation. The trial also included a high-fish intake
      reference group (n = 53). Ninety-eight children were followed-up with blood
      pressure and anthropometry measurements at 7 y. Diet and physical activity level
      (PAL) were assessed by 4-d weighed dietary records and ActiReg. The PAL value was
      4% lower (P = 0.048) and energy intake (EI) of the boys was 1.1 +/- 0.4 MJ/d
      higher (P = 0.014) in the FO group than in the OO group. Starch intake was 15 +/-
      6 g/d higher (P = 0.012) in the FO group, but there were no other differences in
      diet. Body composition did not differ between the randomized groups with or
      without adjustment for starch intake, EI, and PAL. FO boys had 6 mm Hg higher
      diastolic and mean arterial blood pressure than OO boys (P < 0.01), but girls did
      not differ. Within the randomized groups, blood pressure was not correlated with
      maternal RBC (n-3) LCPUFA after the intervention, but PAL values were (r = 
      0.277; P = 0.038). We previously found higher BMI at 2.5 y in the FO group, but
      the difference did not persist. The differences in blood pressure, EI, and PAL,
      particularly among boys, suggest that early (n-3) LCPUFA intake may have adverse
      effects, which should be investigated in future studies.

PMID- 19091802
TI  - Are stem cells inherently more prone to cryopreservation-induced apoptosis
      compared to ordinary somatic cells?

PMID- 19091801
TI  - Fruit and vegetable intakes are associated with lower risk of colorectal
      adenomas.
AB  - Many phytochemicals in fruits and vegetables have been shown to have cancer
      inhibitory effects in animal studies. These effects on cancer, however, have not
      been clearly demonstrated in human studies. This study investigated the
      association between fruit and vegetable intakes and the risk of adenomatous
      polyps. Participants were part of the Tennessee Colorectal Polyp Study. Eligible
      participants aged 40-75 y were recruited from patients undergoing colonoscopy at
      2 medical centers in Nashville, Tennessee from 2003 to 2005. Cases had at least
      one adenoma and controls were polyp free. Dietary intake was assessed using a
      self-administered FFQ. Associations between dietary intakes and adenoma risk were
      evaluated using unconditional logistic regression with restricted cubic function
      spline. In multivariate analyses of 764 cases and 1517 controls, increased
      intakes of total fruits, berries, fruit juice, and green leafy vegetables were
      associated with reduced adenoma risk. The odds ratio for upper tertile intake
      compared with lower was 0.66 (95% CI = 0.51-0.86) for total fruits, 0.64 (95% CI
      = 0.47-0.87) for berries, 0.72 (95% CI = 0.56-0.92) for fruit juice, and 0.74
      (95% CI = 0.58-0.96) for green vegetables. This study provides additional
      evidence that high total fruit intake and certain fruit and vegetable intakes may
      be associated with a reduced risk of colorectal adenomas.

PMID- 19091803
TI  - Ethanol exposure induces differential microRNA and target gene expression and
      teratogenic effects which can be suppressed by folic acid supplementation.
AB  - BACKGROUND: microRNAs (miRNAs) play an important role in development and are
      associated with birth defects. Data are scant on the role of miRNAs in birth
      defects arising from exposure to environmental factors such as alcohol. METHODS:
      In this study, we determined the expression levels of 509 mature miRNAs in fetal
      mouse brains with or without prenatal ethanol exposure using a miRNA microarray
      technique, verified by northern blot and PCR. Mouse embryos in culture were used
      to examine the effect of ethanol treatment on expression of the putative target
      genes of miR-10a (Hoxa1 and other Hox members) at mRNA and protein level. Open
      field and Morris water maze tests were also performed at post-natal day 35.
      RESULTS: Ethanol treatment induced major fetal teratogenesis in mice and caused
      mental retardation in their offspring, namely lower locomotor activity (P < 0.01)
      and impaired task acquisition. Of the screened miRNAs, miR-10a, miR-10b, miR-9,
      miR-145, miR-30a-3p and miR-152 were up-regulated (fold change >1.5) in fetal
      brains with prenatal ethanol exposure, whereas miR-200a, miR-496, miR-296, miR
      30e-5p, miR-362, miR-339, miR-29c and miR-154 were down-regulated (fold change
      <0.67). Both miR-10a and miR-10b were significantly up-regulated (P < 0.01) in
      brain after prenatal ethanol exposure. Ethanol treatment also caused major
      obstruction in the development of cultured embryos, with down-regulated Hoxa1. Co
      incubation with folic acid blocked ethanol-induced teratogenesis, with up
      regulated Hoxa1 and down-regulated miR-10a (P < 0.01). CONCLUSIONS: The study
      provided new insights into the role of miRNAs and their target genes in the
      pathogenesis of fetal alcohol syndrome.

PMID- 19091804
TI  - Report from a multi-institutional randomized clinical trial examining computer
      assisted problem-solving skills training for English- and Spanish-speaking
      mothers of children with newly diagnosed cancer.
AB  - OBJECTIVES: To evaluate the feasibility and efficacy of a handheld personal
      digital assistant (PDA)-based supplement for maternal Problem-Solving Skills
      Training (PSST) and to explore Spanish-speaking mothers' experiences with it.
      METHODS: Mothers (n = 197) of children with newly diagnosed cancer were
      randomized to traditional PSST or PSST + PDA 8-week programs. Participants
      completed the Social Problem-Solving Inventory-Revised, Beck Depression Inventory
      II, Profile of Mood States, and Impact of Event Scale-Revised pre-, post
      treatment, and 3 months after completion of the intervention. Mothers also rated
      optimism, logic, and confidence in the intervention and technology. RESULTS: Both
      groups demonstrated significant positive change over time on all psychosocial
      measures. No between-group differences emerged. Despite technological "glitches,"
      mothers expressed moderately high optimism, appreciation for logic, and
      confidence in both interventions and rated the PDA-based program favorably.
      Technology appealed to all Spanish-speaking mothers, with younger mothers showing
      greater proficiency. CONCLUSIONS: Well-designed, supported technology holds
      promise for enhancing psychological interventions.

PMID- 19091805
TI  - Body dissatisfaction, weight criticism, and self-reported physical activity in
      preadolescent children.
AB  - OBJECTIVE: To examine the associations among physical activity, weight criticism
      during physical activity, and body dissatisfaction in a sample of pre-adolescent
      children. METHODS: A community sample of 376 fifth- and sixth-grade students (M
      age = 10.8, SD = 0.65) completed measures of physical activity, weight criticism
      during physical activity, and body dissatisfaction. RESULTS: Girls who reported
      experiencing high levels of weight criticism and high body dissatisfaction
      engaged in significantly fewer vigorous activities than girls who experienced
      criticism in the absence of body dissatisfaction. These results were not evident
      among boys. CONCLUSIONS: These findings highlight the importance of body
      dissatisfaction in girls' propensity to engage in physical activity, and lend
      preliminary support to obesity prevention efforts that address body
      dissatisfaction and weight criticism among girls.

PMID- 19091806
TI  - Conducting a randomized clinical trial of an psychological intervention for
      parents/caregivers of children with cancer shortly after diagnosis.
AB  - OBJECTIVE: To report acceptability, feasibility, and outcome data from a
      randomized clinical trial (RCT) of a brief intervention for caregivers of
      children newly diagnosed with cancer. METHOD: Eighty-one families were randomly
      assigned following collection of baseline data to Intervention or Treatment as
      Usual (TAU). Recruitment and retention rates and progression through the protocol
      were tracked. Measures of state anxiety and posttraumatic stress symptoms served
      as outcomes. RESULTS: Difficulties enrolling participants included a high
      percentage of newly diagnosed families failing to meet inclusion criteria (40%)
      and an unexpectedly low participation rate (23%). However, movement through the
      protocol was generally completed in a timely manner and those completing the
      intervention provided positive feedback. Outcome data showed no significant
      differences between the arms of the RCT. CONCLUSIONS: There are many challenges
      inherent in conducting a RCT shortly after cancer diagnosis. Consideration of
      alternative research designs and optimal timing for interventions are essential
      next steps.

PMID- 19091807
TI  - Using a website to build community and enhance outcomes in a group, multi
      component intervention promoting healthy diet and exercise in adolescents.
AB  - OBJECTIVE: This article describes website use and behavioral outcomes in a multi
      component lifestyle intervention promoting healthy diet and exercise. METHODS: A
      2-year randomized clinical trial to improve bone density in 228 adolescent girls,
      the intervention included a website designed to enhance intervention adherence,
      retention of participants, and behavioral outcomes. Measures included diet and
      exercise recalls, surveys, and web-usage data. RESULTS: Website use was
      associated with increases in calcium intake (ss = 69.72, p =.01, ES = 0.15) and
      high-impact activity (ss = 10.93, p =.04, ES =.13). Use of web pages related to
      behavioral feedback and communications was not significantly associated with
      behavioral outcomes. The most visited website pages had content related to
      incentive points, caption contests, and fun facts. CONCLUSIONS: Web elements of a
      multi-component intervention may promote retention and engagement in target
      behaviors. Such websites may be most acceptable to adolescent participants if
      they blend fun and behavioral elements, rather than exclusively focusing on
      behavioral changes.

PMID- 19091808
TI  - Performance of the TREAT decision support system in an environment with a low
      prevalence of resistant pathogens.
AB  - OBJECTIVES: To evaluate a decision support system (TREAT) for guidance of
      empirical antimicrobial therapy in an environment with a low prevalence of
      resistant pathogens. METHODS: A retrospective trial of TREAT has been performed
      at Copenhagen University, Hvidovre Hospital. The cohort of patients included
      adults with systemic inflammation and suspicion of community-acquired bacterial
      infection. The empirical antimicrobial treatment recommended by TREAT was
      compared with the empirical antimicrobial treatment prescribed by the first
      attending clinical physician. RESULTS: Out of 171 patients recruited, 161 (65
      with microbiologically documented infections) fulfilled the inclusion criteria of
      TREAT. Coverage achieved by TREAT was significantly higher than that by clinical
      practice (86% versus 66%, P = 0.007). There was no significant difference in the
      cost of future resistance between treatments chosen by TREAT and those by
      physicians. The direct expenses for antimicrobials were higher in TREAT when
      including patients without antimicrobial treatment, while there was no
      significant difference otherwise. The cost of side effects was significantly
      lower using TREAT. CONCLUSIONS: The results of the study suggest that TREAT can
      improve the appropriateness of antimicrobial therapy and reduce the cost of side
      effects in regions with a low prevalence of resistant pathogens, however, at the
      expense of increased use of antibiotics.

PMID- 19091809
TI  - Design of an air sampler for a small unmanned aerial vehicle.
AB  - In the aftermath of a nuclear accident or malevolent act, it is of paramount
      importance to have the capability to monitor airborne radioactive substances by
      collecting air samples. For potentially dangerous missions, the Radiation and
      Nuclear Safety Authority of Finland (STUK) has developed an air sampler to be
      used on a small unmanned aerial vehicle. When a Petrianov or Fluoropore filter is
      used in the sampler and the air velocity is 71 km h(-1), the air flow rate
      through the filter is 0.73 m(3) h(-1) or 0.23 m(3) h(-1), respectively. The
      present article introduces the developed air sampler using fluid dynamic
      simulations and wind tunnel data. The operation of the system was validated by
      collecting airborne radioactive aerosols from air.

PMID- 19091810
TI  - Words count: how interest in stem cells has made the embryo available--a look at
      the French law of bioethics.

PMID- 19091811
TI  - Fourteen years of severe arthralgia in a man without gastrointestinal symptoms:
      atypical Whipple's disease.
AB  - We report here the case of Whipple's disease in a 60-year-old man with severe
      arthralgia and systemic disorders but without gastrointestinal manifestations.
      The patient had different clinical diagnoses over a period of 14 years. We
      identified Tropheryma whipplei by real-time PCR. Molecular typing was also
      performed by sequencing the 16S-23S rRNA intergenic spacer region and domain III
      of the 23S rRNA gene.

PMID- 19091812
TI  - Association of high Orientia tsutsugamushi DNA loads with disease of greater
      severity in adults with scrub typhus.
AB  - Orientia tsutsugamushi, the cause of scrub typhus, is a major pathogen in the
      Asia-Pacific region. The severity of infection ranges from mild features to
      multiorgan failure and death. The aim of this prospective study was to define the
      O. tsutsugamushi loads in the blood samples of patients with scrub typhus on the
      day of hospital admission and to determine whether this was associated with
      disease severity. Quantitation was performed using a real-time PCR assay
      targeting the 16S rRNA gene of O. tsutsugamushi. A total of 155 patients with a
      confirmed diagnosis of scrub typhus had a median (interquartile range [IQR],
      range) O. tsutsugamushi DNA load in blood of 13 (0 to 334, 0 to 310,253)
      copies/ml. This included 74 patients who had undetectable bacterial loads. An
      analysis of bacterial load versus clinical features for all 155 patents
      demonstrated that duration of illness (P < 0.001), presence of eschar (P =
      0.004), and concentrations of aspartate aminotransferase, alanine
      aminotransferase, and alkaline phosphatase (P < 0.001 for all three) were
      positively correlated with bacterial load. Patients who died had a significantly
      higher bacterial load than those who survived (mean [standard deviation] values:
      17,154 [12.7] versus 281 [5.2] copies/ml; P < 0.001). This study has demonstrated
      a relationship between bacterial load and disease severity in adults with scrub
      typhus.

PMID- 19091813
TI  - Utility of pyrosequencing in identifying bacteria directly from positive blood
      culture bottles.
AB  - Growth in liquid media is the gold standard for detecting microorganisms
      associated with bloodstream infections. The Gram stain provides the first clue as
      to the etiology of infection, with phenotypic identification completed 1 or 2
      days later. Providing more detailed information than the Gram stain can impart,
      and in less time than subculturing, would allow the use of more directed
      empirical therapy and, thus, reduce the patient's exposure to unnecessary or
      ineffective antibiotics sooner. The study had two objectives, as follows: (i) to
      identify new targets to improve our ability to differentiate among certain
      enteric gram-negative rods or among certain Streptococcus species and (ii) to
      determine whether real-time PCR and pyrosequencing could as accurately identify
      organisms directly from positive blood culture bottles as culture-based methods.
      Two hundred and fifty-five consecutive positive blood culture bottles were
      included. The results showed a high level of agreement between the two
      approaches; of the 270 bacteria isolated from the 255 blood culture bottles,
      results for pyrosequencing and culture-based identifications were concordant for
      264/270 (97.8%) bacteria with three failed sequences, and three sequences without
      match. Additionally, compared to the universal 16S rRNA gene target, the new 23S
      rRNA gene targets greatly improved our ability to differentiate among certain
      enteric gram-negative rods or among certain Streptococcus species. In conclusion,
      combining real-time PCR and pyrosequencing provided valuable information beyond
      that derived from the initial Gram stain and in less time than phenotypic culture
      based identification. This strategy, if implemented, could result in a more
      directed empirical therapy in patients and would promote responsible antibiotic
      stewardship.

PMID- 19091814
TI  - B:2a:p1.5 meningococcal strains likely arisen from capsular switching event still
      spreading in Spain.
AB  - Eighteen clustered cases of meningococcal disease associated with B:2a:P1.5
      strains doubled the annual incidence up to 4.3 x 10(5) in Navarra, Spain, in
      2007. Eleven percent of cases were fatalities, and 74% of cases were individuals
      10 to 24 years old. This is the third cluster associated with this strain in
      northern Spain since 2001.

PMID- 19091815
TI  - In vivo and in vitro alterations in influenza A/H3N2 virus M2 and hemagglutinin
      genes: effect of passage in MDCK-SIAT1 cells and conventional MDCK cells.
AB  - No mutations were detected in the hemagglutinin gene of influenza A/H3N2 virus
      isolates from patients undergoing short-term amantadine treatment. However,
      genetic changes occurred after serial passage in either MDCK or MDCK-SIAT1 cells.
      Our results showed that only a few mutations were observed in MDCK-SIAT1-passaged
      isolates in the presence of amantadine.

PMID- 19091816
TI  - Evaluation and implementation of a chromogenic agar medium for salmonella
      detection in stool in routine laboratory diagnostics.
AB  - We evaluated which chromogenic agar medium for Salmonella detection in stool
      would be most sensitive and specific in our culture protocol. The use of BBL
      CHROMagar Salmonella chromogenic medium combined with xylose-lysine-deoxycholate
      agar yielded a sensitivity of 100% and also reduced workload and costs.

PMID- 19091817
TI  - Molecular diagnostic identification of Staphylococcus pseudintermedius.
AB  - We report the first diagnostic test for the identification of Staphylococcus
      pseudintermedius involving a simple PCR-restriction fragment length polymorphism
      approach. The method allows discrimination of S. pseudintermedius from the
      closely related members of the Staphylococcus intermedius group and other
      important staphylococcal pathogens of humans and dogs.

PMID- 19091818
TI  - Cocirculation of antigenic variants and the vaccine-type virus during the 2004
      2005 influenza B virus epidemics in Japan.
AB  - In the 2004-2005 season, there was a large epidemic of the influenza B virus
      Yamagata group in Kobe, Japan. In hemagglutination inhibition tests, most of the
      clinical isolates from Kobe showed antigenicities similar to those of previous
      isolates (the vaccine-type virus). Only a few antigenic variants were isolated
      around the peak of the epidemic; however, Kobe residents developed antibodies
      against the variants during the season. The antigenic variants showed a one-point
      mutation of a nucleotide in the HA1 gene (C440A or G421A), which resulted in the
      substitution of one amino acid in the 150 loop of the HA molecule (T147N or
      G141R). The 150 loop is one of four epitopes of the hemagglutinin molecule of the
      influenza B virus. We established a system to detect one-point differences in the
      nucleotides of the 150 loop by means of high-resolution melting curve analysis
      with LCGreen. With this system, the isolates were determined to be the vaccine
      type virus, antigenic variants, or a mixture of both. Some isolates were shown to
      be mixtures although they had been recognized as the vaccine-type virus with the
      hemagglutination inhibition tests. Thus, the antigenic variants appeared in the
      early period of the epidemic and were cocirculating with the vaccine-type virus
      during the epidemic.

PMID- 19091820
TI  - Recombinant expression and affinity purification of a novel epididymal human
      sperm-binding protein, BSPH1.
AB  - Mammalian sperm undergo a series of maturation steps before acquiring
      fertilization competence. Our previous work demonstrated the importance of binder
      of sperm (BSP) proteins in bovine sperm capacitation. Recent studies identified a
      BSP-homologous DNA sequence in the human genome (BSPH1) and mRNA expression in
      the epididymis. The aim of this study was to develop an efficient method to
      express and purify recombinant human BSPH1. BSPH1 accumulates in inclusion bodies
      when expressed with an N-terminal hexahistidine tag in BL21 (DE3) Escherichia
      coli cells. Similar to other BSP proteins, BSPH1 contains two fibronectin type-II
      (Fn2) domains, each consisting of two disulfide bonds. Therefore, when expressed
      in Origami B (DE3)pLysS cells, a strain favouring disulfide bond formation, an
      improvement in soluble protein yield was observed. However, protein was
      aggregated, which complicated subsequent purification steps. Expression of
      glutathione-S-transferase-tagged BSPH1 in both cell types also led to
      accumulation in inclusion bodies. Finally, successful production of soluble and
      active protein was achieved when BSPH1 was expressed as a His(6)-thioredoxin
      tagged protein. Recombinant protein bound phosphatidylcholine liposomes, low
      density lipoproteins and human sperm, therefore displayed binding activities
      common to all BSP-family proteins, which may indicate similar biological
      function(s). This approach was also successful in producing the murine orthologue
      of BSPH1 in the soluble and active form. Thus, fusion to thioredoxin and
      expression in Origami B (DE3)pLysS cells may constitute a strategy applicable to
      all BSP-family proteins, and possibly to other proteins containing Fn2 domains.
      This work is important to elucidate the role of BSPH1 in human sperm functions
      and fertility.

PMID- 19091819
TI  - Abbott RealTime hepatitis C virus (HCV) and Roche Cobas AmpliPrep/Cobas TaqMan
      HCV assays for prediction of sustained virological response to pegylated
      interferon and ribavirin in chronic hepatitis C patients.
AB  - Two commercial real-time PCR assays are currently available for sensitive
      hepatitis C virus (HCV) RNA quantification: the Abbott RealTime HCV assay (ART)
      and Roche Cobas AmpliPrep/Cobas TaqMan HCV assay (CAP/CTM). We assessed whether
      the two real-time PCR assays were more effective than Roche Cobas Amplicor HCV
      Monitor test, v.2.0 (CAM) for prediction of the sustained virological response
      (SVR) to pegylated interferon (PEG-IFN) plus ribavirin (RBV) in chronic hepatitis
      C. Sixty patients chronically infected with HCV genotype 1b (37 males and 23
      females, 53 +/- 12 years of age) were treated with PEG-IFNalpha2b plus RBV for 48
      weeks. Stored specimens at nine time points for each patient (at baseline, on
      treatment, and 24 weeks after treatment) were tested by the two real-time PCR
      assays and CAM. Twenty-six (43.3%) patients reached SVR. The positive predictive
      values (PPVs) for SVR of undetectable HCV RNA at week 12 by CAM, ART, and CAP/CTM
      were 74.3%, 88.0%, and 95.2%, respectively. An undetectable HCV RNA level by CAM,
      ART, and CAP/CTM correctly predicted SVR at week 4 in 100%, 100%, and 100% of
      patients, at weeks 5 to 8 in 91.7%, 100%, and 100% of patients, at weeks 9 to 12
      in 55.6%, 75%, and 87.5% of patients, and at weeks 13 to 24 in 0%, 26.7%, and 40%
      of patients, respectively. Of 16 patients who relapsed after treatment, HCV RNA
      was detectable in 2 patients at the end of treatment by CAP/CTM but undetectable
      by ART and CAM. HCV RNA tests using ART and CAP/CTM are considered to be more
      effective at predicting SVR than CAM, and the PPV for SVR was slightly higher in
      CAP/CTM than in ART.

PMID- 19091821
TI  - Prospective randomised multi-centre trial comparing the clinical efficacy, safety
      and patient acceptability of circular stapled anopexy with closed diathermy
      haemorrhoidectomy.
AB  - OBJECTIVE: Unlike excisional haemorrhoidectomy, stapled anopexy (SA), which does
      not involve radical excision, has theoretical advantages, thus offering potential
      patient benefits. We compared the clinical efficacy, safety and patient
      acceptability of SA, with closed haemorrhoidectomy (CH). PATIENTS AND METHODS:
      182 patients with symptomatic haemorrhoids (grades II, III, IV) were randomly
      assigned to receive SA or CH and were followed for up to 1 year (6, 12, 24, 48
      weeks) after operation. Postoperative pain, symptom control, complications, re
      treatment rates, patient satisfaction, and quality of life were compared on an
      intention-to-treat basis. RESULTS: Postoperative pain in the SA group (n = 91)
      was significantly lower (p = 0.004, Mann-Whitney U test). At 1 year there were no
      significant differences in the symptom load, symptom severity or the disease
      severity between the two groups. Overall complication rates were similar but
      faecal urgency was reported more frequently following SA (p = 0.093, Fisher's
      exact test). Despite a similar rate of residual symptoms, prolapse control was
      better with CH (p = 0.087, Fisher's exact test), and more patients in the SA
      group required re-treatment for residual prolapse at 1 year (p = 0.037, Fisher's
      exact test). However, more patients rated SA as an excellent operation at 6 and
      12 weeks (p = 0.008 and 0.033, binary logistic regression) and were willing to
      undergo a repeat procedure if required (p = 0.018, Fisher's exact test).
      CONCLUSION: Stapled anopexy offers a significantly less painful alternative to
      excisional haemorrhoidectomy and achieves a higher patient acceptability.
      Although the overall symptom control and safety are similar in the majority of
      the patients, the re-treatment rate for recurrent prolapse at 1 year is higher
      following SA when compared to CH.

PMID- 19091822
TI  - Stem and progenitor cells for liver repopulation: can we standardise the process
      from bench to bedside?
AB  - There has been recent progress in the isolation and characterisation of
      stem/progenitor cells that may differentiate towards the hepatic lineage. This
      has raised expectations that therapy of genetic or acquired liver disease might
      be possible by transplanting stem/progenitor cells or their liver-committed
      progeny. However, it is currently impossible to determine from the many
      documented studies which of the stem/progenitor cell populations are the best for
      therapy of a given disease. This is largely because of the great variability in
      methods used to characterise cells and their differentiation ability, variability
      in transplantation models and inconsistent methods to determine the effect of
      cell grafting in vivo. This manuscript represents a first proposal, created by a
      group of investigators ranging from basic biologists to clinical hepatologists.
      It aims to define standardised methods to assess stem/progenitor cells or their
      hepatic lineage-committed progeny that could be used for cell therapy in liver
      disease. Furthermore standardisation is suggested both for preclinical animal
      models to evaluate the ability of such cells to repopulate the liver
      functionally, and for the ongoing clinical trials using mature hepatocytes. Only
      when these measures have been put in place will the promise of stem/progenitor
      derived hepatocyte-based therapies become reality.

PMID- 19091823
TI  - The efficacy of probiotics in the treatment of irritable bowel syndrome: a
      systematic review.
AB  - INTRODUCTION: Probiotics may benefit irritable bowel syndrome (IBS) symptoms, but
      randomised controlled trials (RCTs) have been conflicting; therefore a systematic
      review was conducted. METHODS: MEDLINE (1966 to May 2008), EMBASE (1988 to May
      2008) and the Cochrane Controlled Trials Register (2008) electronic databases
      were searched, as were abstracts from DDW (Digestive Diseases Week) and UEGW
      (United European Gastroenterology Week), and authors were contacted for extra
      information. Only parallel group RCTs with at least 1 week of treatment comparing
      probiotics with placebo or no treatment in adults with IBS according to any
      acceptable definition were included. Studies had to provide improvement in
      abdominal pain or global IBS symptoms as an outcome. Eligibility assessment and
      data extraction were performed by two independent researchers. Data were
      synthesised using relative risk (RR) of symptoms not improving for dichotomous
      data and standardised mean difference (SMD) for continuous data using random
      effects models. RESULTS: 19 RCTs (18 papers) in 1650 patients with IBS were
      identified. Trial quality was generally good, with nine reporting adequate
      methods of randomisation and six a method of concealment of allocation. There
      were 10 RCTs involving 918 patients providing outcomes as a dichotomous variable.
      Probiotics were statistically significantly better than placebo (RR of IBS not
      improving=0.71; 95% CI 0.57 to 0.88) with a number needed to treat (NNT)=4 (95%
      CI 3 to 12.5). There was significant heterogeneity (chi(2)=28.3, p=0.001,
      I(2)=68%) and possible funnel plot asymmetry. Fifteen trials assessing 1351
      patients reported on improvement in IBS score as a continuous outcome (SMD=-0.34;
      95% CI -0.60 to -0.07). There was statistically significant heterogeneity
      (chi(2)=67.04, p<0.001, I(2)=79%), but this was explained by one outlying trial.
      CONCLUSION: Probiotics appear to be efficacious in IBS, but the magnitude of
      benefit and the most effective species and strain are uncertain.

PMID- 19091824
TI  - Epigenetic changes wipe out protective mechanisms in Barrett's oesophagus.

PMID- 19091825
TI  - Chronic intestinal pseudo-obstruction: how important is JC virus infection?

PMID- 19091826
TI  - After budesonide, what next for collagenous colitis?

PMID- 19091827
TI  - How can a large gallstone give rise to chronic diarrhoea?

PMID- 19091828
TI  - Abdominal pain after attempted endoscopic mucosal resection of a right-sided
      colonic lesion.

PMID- 19091829
TI  - A rare cause of portal hypertension.

PMID- 19091830
TI  - Rapid-onset febrile dermatosis.

PMID- 19091831
TI  - Biomarkers of response to therapy in oesophago-gastric cancer.
AB  - Cancer of the oesophagus, gastro-oesophageal junction (GOJ) and stomach remains a
      major health problem worldwide. The evidence base for the optimal management of
      patients with operable oesophago-gastric cancer is evolving. Accepted approaches
      include preoperative chemotherapy followed by surgery (oesophageal cancer), chemo
      radiotherapy alone (oesophageal cancer) and perioperative chemotherapy (gastric
      and gastro-oesophageal adenocarcinomas). The underlying principles behind
      neoadjuvant therapy are to improve resectability of the tumour by tumour
      shrinkage/downstaging and to treat occult metastatic disease as early as
      possible. The response rate to cytotoxic therapy is about 40% in oesophago
      gastric cancer. Available evidence suggests that a favourable histopathological
      response to cytotoxic therapy may be a useful positive predictive marker in
      oesophago-gastric cancer. However, the ability to predict tumour response in
      routine clinical practice is difficult and is an area of intense investigation.
      There is evolving evidence for the role of predictive biomarkers in cancer in
      general and oesophago-gastric cancer in particular. We provide an overview on the
      current status of radiological and biological predictive biomarkers. We have
      focussed on clinical translational investigations and, where appropriate,
      provided pre-clinical insights. Whether predictive markers will be routinely
      incorporated in clinical practice remains to be seen as biomarker research is
      expensive and the data generated from these investigations are complex. It is
      clear that a concerted international effort between academia and industry is
      critical if personalised medicine as a practical reality for our cancer patients
      is to be realised.

PMID- 19091833
TI  - Does antidepressant medication in patients with hepatitis C undergoing interferon
      alpha treatment reduce therapeutic efficacy?

PMID- 19091835
TI  - Letter in response to 'Unacceptable variation in abdominoperineal excision rates
      for rectal cancer: time to intervene?'.

PMID- 19091837
TI  - Unacceptable variation in abdominoperineal excision rates for rectal cancer: a
      surgeon's response.

PMID- 19091838
TI  - Fatigue in non-alcoholic fatty liver disease: is there a role for hypothyroidism.

PMID- 19091839
TI  - Fatal invasive pulmonary aspergillosis associated with adalimumab therapy.

PMID- 19091841
TI  - Unacceptable variation in abdominoperineal excision rates for rectal cancer.

PMID- 19091843
TI  - Transient development of anti-mitochondrial antibodies accompanies autoimmune
      hepatitis-sclerosing cholangitis overlap.

PMID- 19091844
TI  - The type of the patient should be considered on discontinuation of anticoagulant
      and antiplatelet therapy.

PMID- 19091845
TI  - No TGFBRII germline mutations in juvenile polyposis patients without SMAD4 or
      BMPR1A mutation.

PMID- 19091847
TI  - Dyspnoea in a patient with cirrhosis.

PMID- 19091848
TI  - Cataract surgical coverage remains lower in women.
AB  - BACKGROUND: Cataract remains the leading cause of global blindness. Evidence from
      population-based surveys, carried out up to 2000, and the launch of the VISION
      2020 initiative to address avoidable blindness showed that women in low- and
      middle-income countries had a lower cataract surgical coverage (CSC) than men.
      METHODS: A systematic review identified population-based surveys reporting CSC in
      low- and middle-income countries published since 2000. Researchers extracted data
      on sex-specific CSC rates and estimated the overall CSC differences using meta
      analyses. RESULTS: Among the 23 surveys selected for this review, 21 showed
      higher CSC among men. The Peto odds ratio revealed that men were 1.71 times (95%
      CI 1.48 to 1.97) more likely to have cataract surgery than women. The risk
      difference in the rates of surgery varied from -0.025 to 0.276, and the combined
      average was 0.116 (95% CI 0.082 to 0.149). DISCUSSION: Gender inequity in use of
      cataract surgical services persists in the low- and middle-income countries. It
      is estimated in this study that blindness and severe visual impairment from
      cataract could be reduced by around 11% in the low- and middle-income countries
      if women were to receive cataract surgery at the same rate as men. Additional
      effort globally is needed to ensure that women receive the benefits of cataract
      surgery at the same rate as men.

PMID- 19091849
TI  - Evaluation of keratic precipitates and corneal endothelium in Fuchs'
      heterochromic cyclitis by in vivo confocal microscopy.
AB  - PURPOSE: To analyse keratic precipitates in Fuchs' heterochromic cyclitis (FHC)
      by in-vivo confocal microscopy (IVCM). PATIENTS AND METHODS: A retrospective
      chart review of 13 consecutive patients with FHC was conducted. Data collection
      included medical and ophthalmological history, age, age at diagnosis, gender,
      detailed slit-lamp examination and IVCM images. The IVCM characteristics of
      keratic precipitates and of the endothelium were analysed. RESULTS: Large
      hyperreflective deposits corresponding to keratic precipitates were observed on
      the endothelium of all FHC eyes and showed a great consistency among the
      different patients. These infiltrating keratic precipitates had a dendritic
      shape, with a small central core with numerous thin pseudopodia sometimes making
      connection between different keratic precipitates. The mean density of these
      keratic precipitates was 16.01/mm(2) (SD 6.54). The mean size of the largest
      dimension of these keratic precipitates was 127.31 microm (SD 41.49; range 66.16
      201.4 microm). Hyporeflective round defects were observed at the level of the
      endothelium at contact or in the close vicinity of keratic precipitates or
      smaller hyperreflective deposits. All contralateral (non-affected eyes) had no
      keratic precipitates nor endothelial abnormalities. CONCLUSIONS: By providing
      high resolution images of corneal endothelium and keratic precipitates, IVCM
      could help the diagnosis and understanding of complex forms of intraocular
      inflammation such as FHC.

PMID- 19091850
TI  - Socio-economic deprivation and visual acuity at presentation in exudative age
      related macular degeneration.
AB  - AIM: To evaluate the influence of socio-economic factors on visual acuity (VA) at
      presentation in exudative age-related macular degeneration (AMD). METHODS: The
      medical records of all consecutive patients with newly diagnosed exudative AMD
      examined at the Ophthalmology Departments of Grampian University Hospitals-NHS
      Trust, Aberdeen, and Gartnavel General Hospital, Glasgow, between July 2004 and
      June 2005, were reviewed. Demographics, duration of symptoms, VA in study and
      fellow eye, exudative AMD characteristics, status of fellow eye and patient home
      address, used to determine the Scottish Index of Multiple Deprivation (SIMD)
      score, were recorded. The effect of these parameters on VA at presentation was
      investigated using general linear modelling. RESULTS: Two-hundred and forty
      patients (median age 79 years) were included in this study; 44 (18.3%) belonged
      to the lowest 20% SIMD score (most deprived). Age and location and type of the
      choroidal neovascularisation were statistically significantly associated with VA
      at presentation (p = 0.003, p<0.001 and p<0.001, respectively). SIMD scores (p =
      0.959), area (Glasgow/Aberdeen) (0.247) and VA in the fellow eye (p = 0.056) were
      not associated with presenting vision. CONCLUSIONS: Age, location and type of
      choroidal neovascularisation, but not socio-economic deprivation, were associated
      with VA at presentation in exudative AMD.

PMID- 19091851
TI  - Intravitreal bevacizumab to treat subfoveal choroidal neovascularisation in
      highly myopic eyes: 1-year outcome.
AB  - AIMS: The aim of the study was to examine the changes in visual acuity,
      fluorescein angiography (FA) and optical coherence tomography (OCT) macular
      thickness of subfoveal, and juxtafoveal choroidal neovascularisation (CNV) in
      highly myopic eyes treated by intravitreal bevacizumab. METHODS: The study was a
      prospective, non-randomised, multicentre, interventional case series. Twenty-nine
      highly myopic eyes from 28 patients with subfoveal and juxtafoveal CNV were
      treated by three monthly intravitreal injections of 1.25 mg bevacizumab. Patients
      were evaluated for best-corrected visual acuity (BCVA) and OCT at baseline and
      then monthly for 1 year. FA was performed at baseline, after 3 months, and
      whenever CNV activity was suspected. RESULTS: The average age was 50 (SD 15,
      range 29-82) years. The mean LogMAR BCVA at baseline was 0.55 (SD 0.25, range 0.2
      1.0) and 0.38 (SD 0.32, range 0.0-1.2) at 1 year. Sixteen eyes were naive for
      treatment and 13 eyes had been previously treated by photodynamic therapy
      (average 2.5 sessions). Leakage from CNV had ceased in all eyes at month 3. OCT
      central foveal thickness decreased significantly from 282 (SD 68) mum at baseline
      to 224 (SD 46) mum at month 12 (p = 0.008, Student t test for paired data). Six
      eyes needed one re-injection during follow-up at month 4 (one eye), month 6 (four
      eyes) and month 12 (one eye). Neither ocular nor systemic adverse reactions
      appeared during follow-up. CONCLUSIONS: The results of this case series suggest
      that intravitreal bevacizumab seems to be an effective therapeutic procedure to
      treat subfoveal and juxtafoveal CNV in highly myopic eyes at 1-year follow-up.
      Further studies are required to verify the efficacy and usefulness of this
      therapy compared with established treatments for this condition.

PMID- 19091852
TI  - Ocular tilt reaction and internuclear ophthalmoplegia associated with venous
      sinus thrombosis: an unusual case.

PMID- 19091853
TI  - Pharmacogenetics of complement factor H (Y402H) and treatment of exudative age
      related macular degeneration with ranibizumab.
AB  - AIMS: To determine whether complement factor H (CFH) genotypes have a
      pharmacogenetic effect on the treatment of exudative age-related macular
      degeneration (AMD) with ranibizumab. METHODS: A retrospective study of 156
      patients with exudative AMD treated with intravitreal ranibizumab monotherapy was
      conducted. AMD phenotypes were characterised by clinical examination, visual
      acuity, fundus photography, fluorescein angiography and injection timing.
      Patients received intravitreal ranibizumab injections as part of routine
      ophthalmological care and were followed for a minimum of 9 months. Each patient
      was genotyped for the single nucleotide polymorphism rs1061170 (Y402H) in the CFH
      gene. RESULTS: Baseline lesion size and angiographic type, as well as mean visual
      acuities at baseline, 6 months, and 9 months were similar among the three CFH
      genotypes. Over 9 months, patients with both risk alleles received approximately
      one more injection (p = 0.09). In a recurrent event analysis, patients homozygous
      for the CFH Y402H risk allele had a 37% significantly higher risk of requiring
      additional ranibizumab injections (p = 0.04). CONCLUSIONS: In this study cohort,
      the response to treatment of AMD with ranibizumab differed according to CFH
      genotype, suggesting that determining patients' CFH genotype may be helpful in
      the future in tailoring treatment for exudative AMD with intravitreal
      ranibizumab.

PMID- 19091854
TI  - CNS metastasis from malignant uveal melanoma: a clinical and histopathological
      characterisation.
AB  - AIM: To characterise uveal melanoma that has metastasised to the central nervous
      system (CNS). METHODS: Review of 2365 patients constituting all patients
      diagnosed as having primary uveal melanoma in Denmark during the period 1943
      1997. All patients with malignant uveal melanoma and metastasis to the CNS were
      identified. For each patient, clinical and histopathological data were gathered.
      RESULTS: Sixteen patients with CNS metastasis were identified. The median age was
      58 years. The majority of CNS metastases were located in the frontal and parietal
      lobes. Eleven patients had widespread metastases. Five patients had exclusively
      metastasis to the CNS. The average time from diagnosis of primary tumour to
      symptoms of CNS metastasis was 91 months. The average time from the initial CNS
      symptoms to death was 20 months. All tumours were composed of either mixed or
      spindle cells. The average largest basal diameter of the primary tumours was 12
      mm. One tumour was a ring melanoma. The majority of tumours had a ruptured Bruch
      membrane. Retinal invasion was observed in 36% of tumours. No specimen had optic
      nerve invasion. Scleral invasion was pronounced in 36% of cases, and extrascleral
      extension was observed in two cases (14%). The amount of tumour infiltrating
      lymphocytes was pronounced in three cases (23%). CONCLUSION: The proportion of
      uveal melanoma patients having CNS metastasis was 0.7%. Eleven patients had
      multiple organ metastases, and the average time from the initial CNS symptoms to
      death was 8 months. Five patients had metastasis to the CNS solely, and the
      average time from the initial CNS symptoms to death was 57 months.

PMID- 19091855
TI  - Histological analysis of retinas sampled during translocation surgery: a
      comparison with normal and transplantation retinas.
AB  - AIMS: To carry out a histopathological analysis of retinal specimens of patients
      undergoing translocation surgery for age-related macular degeneration (ARMD).
      METHODS: A histopathological analysis, using confocal microscopy, was performed
      on six retinal specimens. Results were compared with those from two further
      retinal specimens, collected during RPE transplantation, to control for the
      effects of vitrectomy and ARMD. In addition, a third control specimen from a
      cadaver with no history of ophthalmic disease was also analysed. RESULTS: In the
      translocation specimens, rods and cones were relatively well preserved but showed
      reduced density and outer segment length. In four specimens, there were focal
      areas of rod opsin redistribution to the inner segment, but this was not observed
      in the controls. Staining with calbindin was decreased in cones compared with
      controls but normal in horizontal and amacrine cells. Rod bipolar cells were
      mildly disorganised, and in one there was evidence of neurite sprouting. Glial
      fibrillar acidic protein was raised in both translocation and transplantation
      retinae but not in the cadaver control. CONCLUSIONS: In this study, there was
      little evidence of cellular injury following iatrogenic detachment; however, the
      rate of PVR following translocation surgery infers that cellular events set in
      motion may continue despite early reattachment.

PMID- 19091856
TI  - Prevalence and risk factors for diabetic retinopathy: a population-based
      assessment from Theni District, south India.
AB  - AIMS: To estimate the prevalence of diabetic retinopathy (DR) and the possible
      risk factors associated with DR, in a population of south India. METHODS: A cross
      sectional sample of subjects aged 30 years and older was selected using a cluster
      sampling technique from Theni district of Tamilnadu state. Eligible subjects were
      identified through a door-to-door survey and fasting blood glucose estimation.
      History of diabetes was elicited, and height, weight and blood pressure were
      measured for all subjects. Ocular examinations including visual acuity and
      anterior and posterior segment examinations were performed at preselected sites
      within clusters. RESULTS: Among the 25 969 persons screened for diabetes mellitus
      (DM), 2802 (10.8%) (95% CI 9.3 to 12.2%) were found to have DM. DR was detected
      in 298 (1.2%) of 25 969 subjects. The age-gender-adjusted prevalence of DR is
      0.05% (95% CI 0.04 to 0.06%) for rural and 1.03% (95% CI 0.89 to 1.12%) for urban
      areas. The overall age-gender-cluster adjusted prevalence of DR was 0.74% (95% CI
      0.66 to 0.83%). Diabetic retinopathy was present in 12.2% (95% CI 10.4 to 14.1%)
      of the DM population. CONCLUSION: Adequate training of ophthalmologists in
      treating DR and improvement in eye-care infrastructure are needed to tackle this
      major public health problem in India.

PMID- 19091857
TI  - Predicting the impact of blocking human immunodeficiency virus type 1 Nef in
      vivo.
AB  - Human immunodeficiency virus type 1 (HIV-1) Nef is a multifunctional protein that
      confers an ability to evade killing by cytotoxic T lymphocytes (CTLs) as well as
      other advantages to the virus in vivo. Here we exploited mathematical modeling
      and related statistical methods to estimate the impact of Nef activity on viral
      replication in vivo in relation to CTLs. Our results indicate that downregulation
      of major histocompatibility complex class I (MHC-I) A and B by wild-type Nef
      confers an advantage to the virus of about 82% in decreased CTL killing
      efficiency on average, meaning that abolishing the MHC-I downregulation function
      of Nef would increase killing by more than fivefold. We incorporated this
      estimate, as well as prior estimates of replicative enhancement by Nef, into a
      previously published model of HIV-1 and CTLs in vivo (W. D. Wick, O. O. Yang, L.
      Corey, and S. G. Self, J. Virol. 79:13579-13586, 2005), generalized to permit CTL
      recognition of multiple epitopes. A sequence database analysis revealed that
      92.9% of HIV-1 epitopes are A or B restricted, and a previous study found an
      average of about 19 epitopes recognized (M. M. Addo et al., J. Virol. 77:2081
      2092, 2003). We combined these estimates in the model in order to predict the
      impact of inhibiting Nef function in the general (chronically infected)
      population by a drug. The predicted impact on viral load ranged from negligible
      to 2.4 orders of magnitude, depending on the effects of the drug and the CTL
      dynamical scenario assumed. We conclude that inhibiting Nef could make a
      substantial reduction in disease burden, lengthening the time before the
      necessity of undertaking combination therapy with other antiretroviral drugs.

PMID- 19091858
TI  - Comprehensive profiling of Epstein-Barr virus microRNAs in nasopharyngeal
      carcinoma.
AB  - Epstein-Barr Virus (EBV) establishes a long-term latent infection and is
      associated with a number of human malignancies that are thought to arise from
      deregulation of different stages of the viral life cycle. Recently, a large
      number of microRNAs (miRNAs) have been described for EBV, and it has been
      suggested that their expression may vary between the different latency states
      found in normal and malignant tissue. To date, however, no technique has been
      utilized to comprehensively and quantitatively test this idea by profiling
      expression of the EBV miRNAs in primary infected tissues. We describe here a
      multiplex reverse transcription-PCR assay that allows the profiling of 39 of the
      40 known mature EBV miRNAs from as little as 250 ng of RNA. With this approach,
      we present a comprehensive profile of EBV miRNAs in primary nasopharyngeal
      carcinoma (NPC) tumors including estimates of miRNA copy number per tumor cell.
      This is the first comprehensive profiling of EBV miRNAs in any EBV-associated
      tumor. In contrast to previous suggestions, we show that the BART-derived miRNAs
      are present in a wide range of copy numbers from < or =10(3) per cell in both
      primary tumors and the widely used NPC-derived C666-1 cell line. However, we
      confirm the hypothesis that the BHRF1 miRNAs are not expressed in NPC. Lastly, we
      demonstrate that EBV miRNA expression in the widely used NPC line C666-1 is, with
      some caveats, broadly representative of primary NPC tumors.

PMID- 19091859
TI  - Vacuolar protein sorting pathway contributes to the release of Marburg virus.
AB  - VP40, the major matrix protein of Marburg virus, is the main driving force for
      viral budding. Additionally, cellular factors are likely to play an important
      role in the release of progeny virus. In the present study, we characterized the
      influence of the vacuolar protein sorting (VPS) pathway on the release of virus
      like particles (VLPs), which are induced by Marburg virus VP40. In the
      supernatants of HEK 293 cells expressing VP40, different populations of VLPs with
      either a vesicular or a filamentous morphology were detected. While the filaments
      were almost completely composed of VP40, the vesicular particles additionally
      contained considerable amounts of cellular proteins. In contrast to that in the
      vesicles, the VP40 in the filaments was regularly organized, probably inducing
      the elimination of cellular proteins from the released VLPs. Vesicular particles
      were observed in the supernatants of cells even in the absence of VP40. Mutation
      of the late-domain motif in VP40 resulted in reduced release of filamentous
      particles, and likewise, inhibition of the VPS pathway by expression of a
      dominant-negative (DN) form of VPS4 inhibited the release of filamentous
      particles. In contrast, the release of vesicular particles did not respond
      significantly to the expression of DN VPS4. Like the budding of VLPs, the budding
      of Marburg virus particles was partially inhibited by the expression of DN VPS4.
      While the release of VLPs from VP40-expressing cells is a valuable tool with
      which to investigate the budding of Marburg virus particles, it is important to
      separate filamentous VLPs from vesicular particles, which contain many cellular
      proteins and use a different budding mechanism.

PMID- 19091860
TI  - Proteasomal turnover of hepatitis C virus core protein is regulated by two
      distinct mechanisms: a ubiquitin-dependent mechanism and a ubiquitin-independent
      but PA28gamma-dependent mechanism.
AB  - We have previously reported on the ubiquitylation and degradation of hepatitis C
      virus core protein. Here we demonstrate that proteasomal degradation of the core
      protein is mediated by two distinct mechanisms. One leads to polyubiquitylation,
      in which lysine residues in the N-terminal region are preferential ubiquitylation
      sites. The other is independent of the presence of ubiquitin. Gain- and loss-of
      function analyses using lysineless mutants substantiate the hypothesis that the
      proteasome activator PA28gamma, a binding partner of the core, is involved in the
      ubiquitin-independent degradation of the core protein. Our results suggest that
      turnover of this multifunctional viral protein can be tightly controlled via dual
      ubiquitin-dependent and -independent proteasomal pathways.

PMID- 19091861
TI  - Gene regulation and functional alterations induced by Kaposi's sarcoma-associated
      herpesvirus-encoded ORFK13/vFLIP in endothelial cells.
AB  - Kaposi's sarcoma (KS) is an angioproliferative inflammatory disorder induced by
      endothelial cell infection with the KS-associated herpesvirus (KSHV).
      ORFK13/vFLIP, one of the KSHV genes expressed in KS, encodes a 188-amino-acid
      protein which binds to the Ikappab kinase (IKK) complex to activate NF-kappaB. We
      examined ORFK13/vFLIP contribution to KS phenotype and potential for therapeutic
      targeting. Retroviral transduction of ORFK13/vFLIP into primary human endothelial
      cells induces the spindle morphology distinctive of KS cells and promotes the
      formation of abnormal vascular networks typical of KS vasculature; upregulates
      the expression of proinflammatory cytokines, chemokines, and interferon
      responsive genes; and stimulates the adhesion of inflammatory cells
      characteristic of KS lesions. Thymidine phosphorylase, a cellular enzyme markedly
      induced by ORFK13/vFLIP, can metabolize the prodrug 5-fluoro-5-deoxyuridine (5
      dFUrd) to 5-fluouridine (5-FU), a potent thymidine synthase inhibitor, which
      blocks DNA and RNA synthesis. When tested for cytotoxicity, 5-dFUrd (0.1 to 1
      microM) selectively killed ORFK13/vFLIP-expressing endothelial cells while
      sparing control cells. These results demonstrate that ORFK13/vFLIP directly and
      indirectly contributes to the inflammatory and vascular phenotype of KS and
      identify 5-dFUrd as a potential new drug that targets KSHV latency for the
      treatment of KS and other KSHV-associated malignancies.

PMID- 19091862
TI  - Interaction of human cytomegalovirus pUL84 with casein kinase 2 is required for
      oriLyt-dependent DNA replication.
AB  - Human cytomegalovirus pUL84 is a phosphorylated protein that is required for
      lytic DNA replication and participates in regulation of virus gene expression. We
      previously used a proteomics assay to show that human cytomegalovirus pUL84
      interacts with casein kinase 2 (CK2). We now have demonstrated that pUL84 is a
      substrate for CK2 in vitro, and we have determined that two putative CK2
      phosphorylation sites within pUL84 mediate binding to CK2. Mutation of a
      threonine residue at amino acid (aa) 148 and a serine residue at aa 157 within
      the pUL84 protein resulted in the inability of the protein to interact with the
      CK2alpha subunit in transfected cells. Interaction of pUL84 with CK2 was
      essential for complementation of oriLyt-dependent DNA replication, suggesting
      that phosphorylation is an essential modification.

PMID- 19091863
TI  - ORF30 and ORF34 are essential for expression of late genes in murine
      gammaherpesvirus 68.
AB  - A hallmark of productive infection by DNA viruses is the coupling of viral late
      gene expression to genome replication. Here we report the identification of open
      reading frame 30 (ORF30) and ORF34 as viral trans factors crucial for activating
      late gene transcription following viral DNA replication during lytic infection of
      murine gammaherpesvirus 68 (MHV-68). The mutant virus lacking either ORF30 or
      ORF34 underwent normal DNA replication but failed to express viral late gene
      transcripts, leading to nonproductive infection. In a reporter assay system,
      ORF30 and ORF34 were required for MHV-68 to activate the viral late gene
      promoters. Furthermore, studies using chromatin immunoprecipitation assays showed
      that the recruitment of RNA polymerase II to the viral late promoters during
      lytic infection was significantly reduced in the absence of ORF30 or ORF34.
      Together, the results suggest that ORF30 and ORF34 may play an important role in
      the assembly of the transcription initiation complex at the late gene promoters.
      Our discovery of the viral mutants that uncouple late gene transcription from DNA
      replication lays an important foundation to dissect the mechanism of this
      critical step of gene expression regulation.

PMID- 19091864
TI  - Inhibition of Lassa and Marburg virus production by tetherin.
AB  - Recently, tetherin has been identified as an effective cellular factor that
      prevents the release of human immunodeficiency virus type 1. Here, we show that
      the production of virus-like particles induced by viral matrix proteins of Lassa
      virus or Marburg virus was markedly inhibited by tetherin and that N-linked
      glycosylation of tetherin was dispensable for this antiviral activity. Our data
      also suggest that viral matrix proteins or one or more components that originate
      from host cells are targets of tetherin but that viral surface glycoproteins are
      not. These results suggest that tetherin inhibits the release of a wide variety
      of enveloped viruses from host cells by a common mechanism.

PMID- 19091865
TI  - Mutational analysis of a conserved glutamic acid required for self-catalyzed
      cross-linking of bacteriophage HK97 capsids.
AB  - The capsid of bacteriophage HK97 is stabilized by approximately 400 covalent
      cross-links between subunits which form without any action by external enzymes or
      cofactors. Cross-linking only occurs in fully assembled particles after large
      scale structural changes bring together side chains from three subunits at each
      cross-linking site. Isopeptide cross-links form between asparagine and lysine
      side chains on two subunits. The carboxylate of glutamic acid 363 (E363) from a
      third subunit is found approximately 2.4 A from the isopeptide bond in the partly
      hydrophobic pocket that contains the cross-link. It was previously reported
      without supporting data that changing E363 to alanine abolishes cross-linking,
      suggesting that E363 plays a role in cross-linking. This alanine mutant and six
      additional substitutions for E363 were fully characterized and the proheads
      produced by the mutants were tested for their ability to cross-link under a
      variety of conditions. Aspartic acid and histidine substitutions supported cross
      linking to a significant extent, while alanine, asparagine, glutamine, and
      tyrosine did not, suggesting that residue 363 acts as a proton acceptor during
      cross-linking. These results support a chemical mechanism, not yet fully tested,
      that incorporates this suggestion, as well as features of the structure at the
      cross-link site. The chemically identical isopeptide bonds recently documented in
      bacterial pili have a strikingly similar chemical geometry at their cross-linking
      sites, suggesting a common chemical mechanism with the phage protein, but the
      completely different structures and folds of the two proteins argues that the
      phage capsid and bacterial pilus proteins have achieved shared cross-linking
      chemistry by convergent evolution.

PMID- 19091866
TI  - Structural characterization of the Rous sarcoma virus RNA stability element.
AB  - In eukaryotic cells, an mRNA bearing a premature termination codon (PTC) or an
      abnormally long 3' untranslated region (UTR) is often degraded by the nonsense
      mediated mRNA decay (NMD) pathway. Despite the presence of a 5- to 7-kb 3' UTR,
      unspliced retroviral RNA escapes this degradation. We previously identified the
      Rous sarcoma virus (RSV) stability element (RSE), an RNA element downstream of
      the gag natural translation termination codon that prevents degradation of the
      unspliced viral RNA. Insertion of this element downstream of a PTC in the RSV gag
      gene also inhibits NMD. Using partial RNase digestion and selective 2'-hydroxyl
      acylation analyzed by primer extension (SHAPE) chemistry, we determined the
      secondary structure of this element. Incorporating RNase and SHAPE data into
      structural prediction programs definitively shows that the RSE contains an AU
      rich stretch of about 30 single-stranded nucleotides near the 5' end and two
      substantial stem-loop structures. The overall secondary structure of the RSE
      appears to be conserved among 20 different avian retroviruses. The structural
      aspects of this element will serve as a tool in the future design of cis mutants
      in addressing the mechanism of stabilization.

PMID- 19091867
TI  - Severe acute respiratory syndrome coronavirus protein 6 is required for optimal
      replication.
AB  - Severe acute respiratory syndrome coronavirus (SARS-CoV) encodes several
      accessory proteins of unknown function. One of these proteins, protein 6 (p6),
      which is encoded by ORF6, enhances virus replication when introduced into a
      heterologous murine coronavirus (mouse hepatitis virus [MHV]) but is not
      essential for optimal SARS-CoV replication after infection at a relatively high
      multiplicity of infection (MOI). Here, we reconcile these apparently conflicting
      results by showing that p6 enhances SARS-CoV replication to nearly the same
      extent as when expressed in the context of MHV if cells are infected at a low MOI
      and accelerates disease in mice transgenic for the human SARS-CoV receptor.

PMID- 19091868
TI  - Genome comparison of a nonpathogenic myxoma virus field strain with its ancestor,
      the virulent Lausanne strain.
AB  - One of the best-studied examples of host-virus coevolution is the release of
      myxoma virus (MV) for biological control of European rabbits in Australia and
      Europe. To investigate the genetic basis of MV adaptation to its new host, we
      sequenced the genome of 6918, an attenuated Spanish field strain, and compared it
      with that of Lausanne, the strain originally released in Europe in 1952. Although
      isolated 43 years apart, the genomes were highly conserved (99.95% identical).
      Only 32 of the 159 MV predicted proteins revealed amino acid changes. Four genes
      (M009L, M036L, M135R, and M148R) in 6918 were disrupted by frameshift mutations.

PMID- 19091869
TI  - Transmission networks and population turnover of echovirus 30.
AB  - Globally, echovirus 30 (E30) is one of the most frequently identified
      enteroviruses and a major cause of meningitis. Despite its wide distribution,
      little is known about its transmission networks or the dynamics of its
      recombination and geographical spread. To address this, we have conducted an
      extensive molecular epidemiology and evolutionary study of E30 isolates collected
      over 8 years from a geographically wide sample base (11 European countries, Asia,
      and Australia). 3Dpol sequences fell into several distinct phylogenetic groups,
      interspersed with other species B serotypes, enabling E30 isolates to be
      classified into 38 recombinant forms (RFs). Substitutions in VP1 and 3Dpol
      regions occurred predominantly at synonymous sites (ratio of nonsynonymous to
      synonymous substitutions, 0.05) with VP1 showing a rapid substitution rate of 8.3
      x 10(-3) substitutions per site per year. Recombination frequency was tightly
      correlated with VP1 divergence; viruses differing by evolutionary distances of
      >0.1 (or 6 years divergent evolution) almost invariably (>97%) had different
      3Dpol groups. Frequencies of shared 3Dpol groups additionally correlated with
      geographical distances, with Europe and South Asia showing turnover of entirely
      distinct virus populations. Population turnover of E30 was characterized by
      repeated cycles of emergence, dominance, and disappearance of individual RFs over
      periods of 3 to 5 years, although the existence and nature of evolutionary
      selection underlying these population replacements remain unclear. The occurrence
      of frequent "sporadic" recombinants embedded within VP1 groupings of other RFs
      and the much greater number of 3Dpol groups than separately identifiable VP1
      lineages suggest frequent recombination with an external diverse reservoir of non
      E30 viruses.

PMID- 19091870
TI  - Level of herpes simplex virus type 1 latency correlates with severity of corneal
      scarring and exhaustion of CD8+ T cells in trigeminal ganglia of latently
      infected mice.
AB  - A hallmark of infection with herpes simplex virus type 1 (HSV-1) is the
      establishment of latency in ganglia of the infected individual. During the life
      of the latently infected individual, the virus can occasionally reactivate,
      travel back to the eye, and cause recurrent disease. Indeed, a major cause of
      corneal scarring (CS) is the scarring induced by HSV-1 following reactivation
      from latency. In this study, we evaluated the relationship between the amount of
      CS and the level of the HSV-1 latency-associated transcript (LAT) in trigeminal
      ganglia (TG) of latently infected mice. Our results suggested that the amount of
      CS was not related to the amount of virus replication following primary ocular
      HSV-1 infection, since replication in the eyes was similar in mice that did not
      develop CS, mice that developed CS in just one eye, and mice that developed CS in
      both eyes. In contrast, mice with no CS had significantly less LAT, and thus
      presumably less latency, in their TG than mice that had CS in both eyes. Higher
      CS also correlated with higher levels of mRNAs for PD-1, CD4, CD8, F4/80,
      interleukin-4, gamma interferon, granzyme A, and granzyme B in both cornea and
      TG. These results suggest that (i) the immunopathology induced by HSV-1 infection
      does not correlate with primary virus replication in the eye; (ii) increased CS
      appears to correlate with increased latency in the TG, although the possible
      cause-and-effect relationship is not known; and (iii) increased latency in mouse
      TG correlates with higher levels of PD-1 mRNA, suggesting exhaustion of CD8+ T
      cells.

PMID- 19091871
TI  - Transmission and long-term stability of compensated CD8 escape mutations.
AB  - Human immunodeficiency virus effectively evades CD8(+) T-cell responses through
      the development of CD8 escape mutations. Recent reports documenting reversion of
      transmitted mutations and the impact of specific escape mutations upon viral
      replication suggest that complex forces limit the accumulation of CD8 escape
      mutations at the population level. However, the presence of compensatory
      mutations capable of alleviating the impact of CD8 escape mutations on
      replication capacity may enable their persistence in an HLA-mismatched host.
      Herein, we illustrate the long-term stability of stereotypic escape mutations in
      the immunodominant HLA-B27-restricted epitope KK10 in p24/Gag following
      transmission when accompanied by a specific compensatory mutation.

PMID- 19091872
TI  - Expansion and diversification of the Populus R2R3-MYB family of transcription
      factors.
AB  - The R2R3-MYB proteins comprise one of the largest families of transcription
      factors in plants. R2R3-MYB family members regulate plant-specific processes,
      such as the elaboration of specialized cell types, including xylem, guard cells,
      trichomes, and root hairs, and the biosynthesis of specialized branches of
      metabolism, including phenylpropanoid biosynthesis. As such, R2R3-MYB family
      members are hypothesized to contribute to the emergence of evolutionary
      innovations that have arisen in specific plant lineages. As a first step in
      determining the role played by R2R3-MYB family members in the emergence of
      lineage-specific innovations in the genus Populus, the entire Populus trichocarpa
      R2R3-MYB family was characterized. The Populus R2R3-MYB complement is much larger
      than that found in other angiosperms with fully sequenced genomes. Phylogenetic
      analyses, together with chromosome placement, showed that the expansion of the
      Populus R2R3-MYB family was not only attributable to whole genome duplication but
      also involved selective expansion of specific R2R3-MYB clades. Expansion of the
      Populus R2R3-MYB family prominently involved members with expression patterns
      that suggested a role in specific components of Populus life history, including
      wood formation and reproductive development. An expandable compendium of
      microarray-based expression data (PopGenExpress) and associated Web-based tools
      were developed to better enable within- and between-species comparisons of
      Populus R2R3-MYB gene expression. This resource, which includes intuitive graphic
      visualization of gene expression data across multiple tissues, organs, and
      treatments, is freely available to, and expandable by, scientists wishing to
      better understand the genome biology of Populus, an ecologically dominant and
      economically important forest tree genus.

PMID- 19091873
TI  - MYB108 acts together with MYB24 to regulate jasmonate-mediated stamen maturation
      in Arabidopsis.
AB  - In Arabidopsis (Arabidopsis thaliana), jasmonate is a key signal required for
      stamen and pollen maturation and thus for male fertility. Using transcriptional
      profiling, we have previously identified a set of 13 transcription factors that
      are proposed to be involved in controlling jasmonate responses in stamens. This
      finding suggests that a transcriptional cascade regulates the many developmental
      and biochemical pathways required to ensure fertility; however, the organization
      of this cascade is currently not understood. Here, we provide a genetic
      characterization of the role of MYB108 and map its relationship to MYB21 and
      MYB24, two other transcription factors involved in the jasmonate response in
      Arabidopsis stamens. Transcriptional profiling and analysis of plants expressing
      a MYB108:GUS fusion protein demonstrated that MYB108 expression is largely
      confined to sporophytic tissues of the stamen. Three allelic myb108 mutants
      exhibited reduced male fertility that was associated with delayed anther
      dehiscence, reduced pollen viability, and decreased fecundity relative to wild
      type. These phenotypes were all found to be exacerbated in myb108 myb24 double
      mutants, which also had shorter stamen filaments. Measurements of MYB108
      transcript levels in wild-type and mutant flowers showed that expression of this
      gene is strongly dependent on MYB21. Taken together, our results indicate that
      MYB108 and MYB24 have overlapping functions and act downstream of MYB21 in a
      transcriptional cascade that mediates stamen and pollen maturation in response to
      jasmonate.

PMID- 19091874
TI  - Analyses of advanced rice anther transcriptomes reveal global tapetum secretory
      functions and potential proteins for lipid exine formation.
AB  - The anthers in flowers perform important functions in sexual reproduction.
      Several recent studies used microarrays to study anther transcriptomes to explore
      genes controlling anther development. To analyze the secretion and other
      functions of the tapetum, we produced transcriptomes of anthers of rice (Oryza
      sativa subsp. japonica) at six progressive developmental stages and pollen with
      sequencing-by-synthesis technology. The transcriptomes included at least 18,000
      unique transcripts, about 25% of which had antisense transcripts. In silico
      anther-minus-pollen subtraction produced transcripts largely unique to the
      tapetum; these transcripts include all the reported tapetum-specific transcripts
      of orthologs in other species. The differential developmental profiles of the
      transcripts and their antisense transcripts signify extensive regulation of gene
      expression in the anther, especially the tapetum, during development. The
      transcriptomes were used to dissect two major cell/biochemical functions of the
      tapetum. First, we categorized and charted the developmental profiles of all
      transcripts encoding secretory proteins present in the cellular exterior; these
      transcripts represent about 12% and 30% of the those transcripts having more than
      100 and 1,000 transcripts per million, respectively. Second, we successfully
      selected from hundreds of transcripts several transcripts encoding potential
      proteins for lipid exine synthesis during early anther development. These
      proteins include cytochrome P450, acyltransferases, and lipid transfer proteins
      in our hypothesized mechanism of exine synthesis in and export from the tapetum.
      Putative functioning of these proteins in exine formation is consistent with
      proteins and metabolites detected in the anther locule fluid obtained by
      micropipetting.

PMID- 19091875
TI  - Histone H2B deubiquitination is required for transcriptional activation of
      FLOWERING LOCUS C and for proper control of flowering in Arabidopsis.
AB  - The spectrum of histone modifications at a given locus is a critical determinant
      for the correct output of gene expression. In Arabidopsis (Arabidopsis thaliana),
      many studies have examined the relationship between histone methylation and gene
      expression, but few studies exist on the relationship between other covalent
      histone modifications and gene expression. In this work, we describe the role of
      histone H2B deubiquitination in the activation of gene expression and the
      consequence of a perturbation of histone H2B deubiquitination in the timing of
      the floral transition in Arabidopsis. A mutation in a H2B deubiquitinase,
      UBIQUITIN-SPECIFIC PROTEASE26 (UBP26), results in an early-flowering phenotype.
      In the ubp26 mutant, mRNA levels of the floral repressor FLOWERING LOCUS C (FLC)
      and other related family members is decreased. Furthermore, this mutant
      accumulates H2B monoubiquitination, and has decreased levels of H3K36
      trimethylation and increased levels of H3K27 trimethylation at the FLC locus.
      Thus, UBP26 is required for transcriptional activation of FLC through H2B
      deubiquitination and is consistent with a model in which deubiquitination is
      necessary for the accumulation of H3K36 trimethylation and the proper level of
      transcriptional activation.

PMID- 19091876
TI  - Myoinositol oxygenase controls the level of myoinositol in Arabidopsis, but does
      not increase ascorbic acid.
AB  - Ascorbic acid (AsA) is a major plant antioxidant. Mutants like vtc1 show a
      reduced AsA concentration, which confirmed by genetic evidence the previously
      proposed AsA pathway via GDP-Man. Here we investigate the role of an animal-like
      alternative biosynthesis route to AsA, starting from the metabolite D-GlcUA,
      which is produced in plants by myoinositol oxygenase (Miox). Miox-overexpressing
      lines have a more than 30-fold up-regulated transcript level and higher enzymatic
      activity as shown by increased incorporation of Miox-derived sugars into cell
      wall polymers. In addition, Miox overexpressors exhibit a lower steady-state
      level of myoinositol and accumulate less myoinositol in feeding experiments due
      to an enhanced turnover rate. The AsA concentration remains the same in wild-type
      and Miox overexpressor lines. Even challenging plants with stress, which
      increases AsA concentration 4-fold, reveals no difference in AsA biosynthesis
      between wild-type and Miox-overexpressing lines. We conclude that D-GlcUA derived
      from the Miox reaction plays a negligible role for AsA biosynthesis. However,
      Miox controls the metabolite level of myoinositol in plants.

PMID- 19091877
TI  - Xanthomonas campestris overcomes Arabidopsis stomatal innate immunity through a
      DSF cell-to-cell signal-regulated virulence factor.
AB  - Pathogen-induced stomatal closure is part of the plant innate immune response.
      Phytopathogens using stomata as a way of entry into the leaf must avoid the
      stomatal response of the host. In this article, we describe a factor secreted by
      the bacterial phytopathogen Xanthomonas campestris pv campestris (Xcc) capable of
      interfering with stomatal closure induced by bacteria or abscisic acid (ABA). We
      found that living Xcc, as well as ethyl acetate extracts from Xcc culture
      supernatants, are capable of reverting stomatal closure induced by bacteria,
      lipopolysaccharide, or ABA. Xcc ethyl acetate extracts also complemented the
      infectivity of Pseudomonas syringae pv tomato (Pst) mutants deficient in the
      production of the coronatine toxin, which is required to overcome stomatal
      defense. By contrast, the rpfF and rpfC mutant strains of Xcc, which are unable
      to respectively synthesize or perceive a diffusible molecule involved in
      bacterial cell-to-cell signaling, were incapable of reverting stomatal closure,
      indicating that suppression of stomatal response by Xcc requires an intact
      rpf/diffusible signal factor system. In addition, we found that guard cell
      specific Arabidopsis (Arabidopsis thaliana) Mitogen-Activated Protein Kinase3
      (MPK3) antisense mutants were unresponsive to bacteria or lipopolysaccharide in
      promotion of stomatal closure, and also more sensitive to Pst coronatine
      deficient mutants, showing that MPK3 is required for stomatal immune response.
      Additionally, we found that, unlike in wild-type Arabidopsis, ABA-induced
      stomatal closure in MPK3 antisense mutants is not affected by Xcc or by extracts
      from Xcc culture supernatants, suggesting that the Xcc factor might target some
      signaling component in the same pathway as MPK3.

PMID- 19091878
TI  - In vivo interference with AtTCP20 function induces severe plant growth
      alterations and deregulates the expression of many genes important for
      development.
AB  - AtTCP20 is a transcription factor belonging to the Arabidopsis (Arabidopsis
      thaliana) TCP-P subfamily, characterized by its capacity to bind to site II
      motifs (TGGGCY). Our aim was to understand the role of AtTCP20 in plant
      development. The expression pattern of a translational fusion of
      Prom(TCP20):CDS20GUSGFP suggested a function for AtTCP20 in several plant organs
      and stages of development. The role of AtTCP20 was challenged in planta by
      inducing expression of AtTCP20 proteins fused with either a transcriptional
      activator domain (VP16) or a repressor domain (EAR). Expression of both modified
      proteins led to severe developmental phenotypes. In-depth analysis suggested that
      AtTCP20 may participate in the regulation of cell expansion, cell division, and
      cell differentiation. Gene expression profiling in roots and hypocotyls revealed
      that 252 genes were down-regulated in both organs after induction of the
      AtTCP20EAR repressor gene. Site II motifs (TGGGCY) were underrepresented in their
      promoters. Conversely, GG(A/T)CCC sequences related to binding sites identified
      for TCP proteins in rice (Oryza sativa) were overrepresented, and a TCP20 fusion
      protein was shown to bind to these sequences in vitro. Gene ontology indicated
      that many targeted genes were involved in cell wall biogenesis and modification
      during expansion and also encoded numerous transcription factors controlling
      plant development. Our results are consistent with the previous proposal that
      AtTCP20 is involved in cell division and growth coordination. Moreover, they
      further suggest that AtTCP20 also contributes to cell expansion control and
      indicate a different involvement of this protein in plant morphogenesis depending
      on the organ and the developmental stage.

PMID- 19091879
TI  - Molecular cloning and characterization of a cDNA for pterocarpan 4
      dimethylallyltransferase catalyzing the key prenylation step in the biosynthesis
      of glyceollin, a soybean phytoalexin.
AB  - Glyceollins are soybean (Glycine max) phytoalexins possessing pterocarpanoid
      skeletons with cyclic ether decoration originating from a C5 prenyl moiety.
      Enzymes involved in glyceollin biosynthesis have been thoroughly characterized
      during the early era of modern plant biochemistry, and many genes encoding
      enzymes of isoflavonoid biosynthesis have been cloned, but some genes for later
      biosynthetic steps are still unidentified. In particular, the prenyltransferase
      responsible for the addition of the dimethylallyl chain to pterocarpan has drawn
      a large amount of attention from many researchers due to the crucial coupling
      process of the polyphenol core and isoprenoid moiety. This study narrowed down
      the candidate genes to three soybean expressed sequence tag sequences homologous
      to genes encoding homogentisate phytyltransferase of the tocopherol biosynthetic
      pathway and identified among them a cDNA encoding dimethylallyl diphosphate:
      (6aS, 11aS)-3,9,6a-trihydroxypterocarpan [(-)-glycinol] 4
      dimethylallyltransferase (G4DT) yielding the direct precursor of glyceollin I.
      The full-length cDNA encoding a protein led by a plastid targeting signal
      sequence was isolated from young soybean seedlings, and the catalytic function of
      the gene product was verified using recombinant yeast microsomes. Expression of
      the G4DT gene was strongly up-regulated in 5 to 24 h after elicitation of
      phytoalexin biosynthesis in cultured soybean cells similarly to genes associated
      with isoflavonoid pathway. The prenyl part of glyceollin I was demonstrated to
      originate from the methylerythritol pathway by a tracer experiment using [1
      (13)C]Glc and nuclear magnetic resonance measurement, which coincided with the
      presumed plastid localization of G4DT. The first identification of a pterocarpan
      specific prenyltransferase provides new insights into plant secondary metabolism
      and in particular those reactions involved in the disease resistance mechanism of
      soybean as the penultimate gene of glyceollin biosynthesis.

PMID- 19091880
TI  - Progressive lipoatrophy after cessation of glatiramer acetate injections: a case
      report.

PMID- 19091881
TI  - Can rate of brain atrophy in multiple sclerosis be explained by clinical and MRI
      characteristics?
AB  - INTRODUCTION: Multiple sclerosis (MS) is characterized, besides focal lesions, by
      brain atrophy. The determinants of atrophy rates in individual patients are
      poorly understood. AIM: This study investigated the predictive value of clinical
      and magnetic resonance imaging (MRI) factors, including short-term changes
      thereof, for concurrent and future atrophy evolution using Spearman's rank
      correlations and stepwise multiple linear regression. METHODS: We retrospectively
      identified a group of 115 active, early relapsing-remitting (RR) patients
      relatively homogeneous in terms of disease course and MRI activity compared to a
      second group of 96 patients with broader spectrum of MS phenotypes and inactive
      scans. All patients had undergone three MRI investigations with interscan
      intervals of at least 12 and 24 months, respectively. RESULTS: In the RR
      patients, 23% of variance in concurrent atrophy rates (over the first interval)
      could be explained by the combination of baseline T2 lesion volume and change in
      EDSS score over the first interval, whereas only 6% in future atrophy rates (over
      the second interval) was explained. In the heterogeneous group, 20.2% of the
      variance in future atrophy rates could be explained, but slightly less in
      concurrent atrophy rates (16.2%). CONCLUSION: We concluded that variance in brain
      atrophy rates can partially be explained by clinical and MRI measures of disease.
      Future atrophy rates in individual MS patients are difficult to predict even when
      including previous atrophy rates.

PMID- 19091882
TI  - Retinal architecture predicts pupillary reflex metrics in MS.
AB  - OBJECTIVE: To study the relation of retinal nerve fiber layer thinning to
      clinical and physiologic measures of visual function in patients with MS or
      neuromyelitis optica and unilateral optic neuropathy. METHODS: We studied a
      cohort of control subjects (n = 64) and patients (n = 24) with evidence of
      unilateral thinning of their average retinal nerve fiber layer as measured by
      optical coherence tomography in order to characterize the relationship between
      ganglion cell axonal degeneration and its impact upon vision and pupillary light
      reflex metrics using infrared pupillometry. RESULTS: When compared to the normal
      fellow eye, and with respect to normal subjects' eyes, we confirmed significant
      abnormalities in retinal nerve fiber layer thickness, total macular volume, low
      contrast letter acuity, and pupillary reflex metrics in the eye with the thinner
      retinal nerve fiber layer. For each -5% change in pupil diameter, there was a
      corresponding 7.1 Amicrom reduction in the average retinal nerve fiber layer
      thickness. There was a significant difference between the pupillary metric of
      percent change in diameter and a decrease in low-contrast letter acuity (P <
      0.001). Each -5% change in pupil diameter was associated with a substantial 3.4
      line loss of low-contrast letter acuity (P < 0.001). Each -5% change in pupil
      diameter was associated with a 0.2 mm(2) decrease in total macular volume (P <
      0.001). CONCLUSION: These findings further corroborate the hypothesis that the
      retina can be utilized as a model to advance our understanding of the mechanisms
      of axonal and neurodegeneration, and the corresponding impact of these processes
      upon the pathophysiology of MS and related disorders.

PMID- 19091884
TI  - Impact of 131I SPECT/spiral CT on nodal staging of differentiated thyroid
      carcinoma at the first radioablation.
AB  - The purpose of this study was to determine the diagnostic value of 131I
      SPECT/spiral CT (SPECT/CT) on nodal staging of patients with thyroid carcinoma at
      the first ablative radioiodine therapy. METHODS: Fifty-seven patients were
      studied using SPECT/CT 3-4 d after receiving 3.96+/-0.5 GBq of 131I for
      radioablation of thyroid remnants after a thyroidectomy for differentiated
      thyroid carcinoma. In addition to planar whole-body scintigraphy, SPECT/CT of the
      neck was performed using a hybrid camera combining a double-head SPECT camera
      with either a 2-slice (n=23) or a 6-slice (n=34) spiral CT scanner. The planar
      scans and the SPECT/CT images were evaluated for cervical tracer uptake
      independently of each other and of the clinical findings. RESULTS: SPECT/CT led
      to a revision of the original diagnosis in 28 of 143 cervical foci of radioiodine
      uptake seen on planar imaging. In particular, SPECT/CT reclassified as benign 6
      of 11 lesions considered to be lymph node metastases and 11 of 15 lesions
      considered to be indeterminate. Furthermore, SPECT/CT allowed the identification
      of 11 lymph node metastases classified as thyroid remnant or as indeterminate on
      planar imaging. Based on this revision, SPECT/CT yielded a gain in information on
      nodal stage in 20 of the 57 patients studied (35%, P<0.03). SPECT/CT altered
      nodal stage from N0 to N1 in 2 of 20 patients and from indeterminate (Nx) to N1
      in 6 of 30 patients. The result was a change in risk stratification conforming to
      the classification proposed by the International Union Against Cancer in 14
      patients (25%). CONCLUSION: SPECT/CT determines lymph node involvement at
      radioablation performed for thyroid cancer more accurately than does planar
      imaging. SPECT/CT may alter management in roughly one quarter of patients with
      thyroid carcinoma by upstaging or downstaging their disease.

PMID- 19091885
TI  - Complementary but distinct roles for MRI and 18F-fluoromisonidazole PET in the
      assessment of human glioblastomas.
AB  - Glioblastoma multiforme is a primary brain tumor known for its rapid
      proliferation, diffuse invasion, and prominent neovasculature and necrosis. This
      study explores the in vivo link between these characteristics and hypoxia by
      comparing the relative spatial geometry of developing vasculature inferred from
      gadolinium-enhanced T1-weighted MRI (T1Gd), edematous tumor extent revealed on T2
      weighted MRI (T2), and hypoxia assessed by 18F-fluoromisonidazole PET (18F
      FMISO). Given the role of hypoxia in upregulating angiogenic factors, we
      hypothesized that the distribution of hypoxia seen on 18F-FMISO is correlated
      spatially and quantitatively with the amount of leaky neovasculature seen on
      T1Gd. METHODS: A total of 24 patients with glioblastoma underwent T1Gd, T2, and
      18F-FMISO-11 studies preceded surgical resection or biopsy, 7 followed surgery
      and preceded radiation therapy, and 11 followed radiation therapy. Abnormal
      regions seen on the MRI scan were segmented, including the necrotic center (T0),
      the region of abnormal blood-brain barrier associated with disrupted vasculature
      (T1Gd), and infiltrating tumor cells and edema (T2). The 18F-FMISO images were
      scaled to the blood 18F-FMISO activity to create tumor-to-blood ratio (T/B)
      images. The hypoxic volume (HV) was defined as the region with T/Bs greater than
      1.2, and the maximum T/B (T/Bmax) was determined by the voxel with the greatest
      T/B value. RESULTS: The HV generally occupied a region straddling the outer edge
      of the T1Gd abnormality and into the T2. A significant correlation between HV and
      the volume of the T1Gd abnormality that relied on the existence of a large
      outlier was observed. However, there was consistent correlation between surface
      areas of all MRI-defined regions and the surface area of the HV. The T/Bmax,
      typically located within the T1Gd region, was independent of the MRI-defined
      tumor size. Univariate survival analysis found the most significant predictors of
      survival to be HV, surface area of HV, surface area of T1Gd, and T/Bmax.
      CONCLUSION: Hypoxia may drive the peripheral growth of glioblastomas. This
      conclusion supports the spatial link between the volumes and surface areas of the
      hypoxic and MRI regions; the magnitude of hypoxia, T/Bmax, remains independent of
      size.

PMID- 19091886
TI  - A new PET scanner with semiconductor detectors enables better identification of
      intratumoral inhomogeneity.
AB  - An autoradiography method revealed intratumoral inhomogeneity in various solid
      tumors. It is becoming increasingly important to estimate intratumoral
      inhomogeneity. However, with low spatial resolution and high scatter noise, it is
      difficult to detect intratumoral inhomogeneity in clinical settings. We developed
      a new PET system with CdTe semiconductor detectors to provide images with high
      spatial resolution and low scatter noise. Both phantom images and patients'
      images were analyzed to evaluate intratumoral inhomogeneity. METHODS: This study
      was performed with a cold spot phantom that had 6-mm-diameter cold sphenoid
      defects, a dual-cylinder phantom with an adjusted concentration of 1:2, and an
      "H"-shaped hot phantom. These were surrounded with water. Phantom images and
      (18)F-FDG PET images of patients with nasopharyngeal cancer were compared with
      conventional bismuth germanate PET images. Profile curves for the phantoms were
      measured as peak-to-valley ratios to define contrast. Intratumoral inhomogeneity
      and tumor edge sharpness were evaluated on the images of the patients. RESULTS:
      The contrast obtained with the semiconductor PET scanner (1.53) was 28% higher
      than that obtained with the conventional scanner (1.20) for the 6-mm-diameter
      cold sphenoid phantom. The contrast obtained with the semiconductor PET scanner
      (1.43) was 27% higher than that obtained with the conventional scanner (1.13) for
      the dual-cylinder phantom. Similarly, the 2-mm cold region between 1-mm hot rods
      was identified only by the new PET scanner and not by the conventional scanner.
      The new PET scanner identified intratumoral inhomogeneity in more detail than the
      conventional scanner in 6 of 10 patients. The tumor edge was sharper on the
      images obtained with the new PET scanner than on those obtained with the
      conventional scanner. CONCLUSION: These phantom and clinical studies suggested
      that this new PET scanner has the potential for better identification of
      intratumoral inhomogeneity, probably because of its high spatial resolution and
      low scatter noise.

PMID- 19091887
TI  - The effectiveness of 18F-FDG PET/CT combined with STIR MRI for diagnosing nodal
      involvement in the thorax.
AB  - The purpose of this study was to compare the efficacy of short-tau inversion
      recovery (STIR) MRI and 18F-FDG PET/CT for the detection of metastasis in
      mediastinal and hilar lymph nodes in patients with lung cancer. METHODS: Ninety
      three patients with known or suspected lung cancer with mediastinal and hilar
      lymph node swelling underwent STIR MRI and 18F-FDG PET/CT examinations. STIR MRI
      scans were obtained with a 2% copper sulfate phantom placed along the back of
      each patient, with the lymph node-to-phantom ratio calculated for quantitative
      analysis. For qualitative analysis, the results of all STIR MRI scans were
      evaluated using a 5-point visual scoring system. To evaluate the diagnostic
      capabilities of STIR MRI and 18F-FDG PET/CT, we used receiver-operating
      characteristic curve analysis to determine the optimal thresholds for the lymph
      node-to-phantom ratio, visual score, and maximal standardized uptake value.
      Further, the capability of each to determine N-stage was compared in each patient
      using the McNemar test. RESULTS: A total of 137 lymph nodes (82 malignant
      lesions, 55 benign lesions) were analyzed. When optimal threshold values were
      adopted, the quantitative and qualitative sensitivity, specificity, and accuracy
      of STIR MRI were not significantly different from those of 18F-FDG PET/CT.
      However, 18F-FDG PET/CT in combination with qualitative STIR MRI analysis had a
      significantly higher capability to detect nodal involvement on an individual
      patient basis (96.9% specificity, 90.3% accuracy) than did 18F-FDG PET/CT alone
      (65.6% specificity, 81.7% accuracy). CONCLUSION: We found that the diagnostic
      capability of STIR MRI was not significantly different from that of 18F-FDG
      PET/CT. However, when those methods were combined, the diagnostic capability for
      N-staging was significantly improved.

PMID- 19091888
TI  - Antibodies and antimatter: the resurgence of immuno-PET.
AB  - The completion of the human genome, coupled with parallel major research efforts
      in proteomics and systems biology, has led to a flood of information on the roles
      of individual genes and proteins in normal physiologic processes and their
      disruptions in disease. In practical terms, this information has opened the door
      to increasingly targeted therapies as specific molecular markers are identified
      and validated. The ongoing transition from empiric to molecular medicine has
      engendered a need for corresponding molecular diagnostics, including noninvasive
      molecular imaging. Convergence of knowledge regarding key biomarkers that define
      normal biologic processes and disease with protein and imaging technology makes
      this an opportune time to revisit the combination of antibodies and PET, or
      immuno-PET.

PMID- 19091889
TI  - Striatal dopamine transporter availability associated with polymorphisms in the
      dopamine transporter gene SLC6A3.
AB  - Polymorphisms in the dopamine transporter (DAT) gene SLC6A3 are associated with
      human striatal DAT expression, but the exact effects on DAT expression are not
      clear. A variable number of tandem repeats (VNTR) in the 3' untranslated region
      of the DAT gene was previously investigated in relation to striatal DAT
      availability, but the results were inconclusive. Other polymorphisms in the DAT
      gene were not extensively studied. Therefore, we investigated whether
      polymorphisms in both 3' and 5' ends of the DAT gene show association with in
      vivo striatal DAT expression. METHODS: The subjects were an ethnically
      homogeneous group of 79 healthy young adults. Striatal DAT availability was
      measured with 123I-(2-beta-carbomethoxy-3-beta(4-iodophenyl)-tropane) (123I-beta
      CIT) SPECT. The 40-base-pair VNTR in the 3' untranslated region of the DAT gene
      and the 2 single nucleotide polymorphisms (SNPs) rs2652511 and rs2937639 in the
      5' end of the DAT gene were genotyped. Multiple-regression analysis was performed
      for each of the 3 polymorphisms. Analysis of the combination of the polymorphisms
      (haplotype analysis) was conducted for the triad rs2652511-rs2937639-VNTR.
      RESULTS: For the VNTR, the 9-repeat (9R) allele was associated with significantly
      higher striatal DAT expression than was the 10-repeat (10R) allele (P=0.002).
      Subanalysis suggested a dominant effect for the 9R allele. Neither SNP rs2652511
      nor SNP rs2937639 was associated with striatal DAT availability. The haplotype T
      A-9R (rs2652511-rs2937639-VNTR) was significantly more associated with higher
      striatal DAT expression than were the other haplotypes (P=0.009). CONCLUSION: The
      DAT VNTR 9R carriers have higher striatal DAT availability than do 10R
      homozygotes. This finding replicates former studies that included healthy
      subjects and also used 123I-beta-CIT SPECT. Our haplotype analysis identified a
      subgroup of 9R carriers, the T-A-9R, which appears to be mainly responsible for
      the association with higher striatal DAT availability. Thus, a combination of
      polymorphisms in both the 3' and the 5' ends of the DAT gene is associated with
      in vivo striatal DAT expression. This finding in healthy subjects may contribute
      to research on DAT availability and genotype in neuropsychiatric disorders.

PMID- 19091890
TI  - P-glycoprotein function at the blood-brain barrier imaged using 11C-N-desmethyl
      loperamide in monkeys.
AB  - 11C-Loperamide is an avid substrate for P-glycoprotein (P-gp), but it is rapidly
      metabolized to 11C-N-desmethyl-loperamide (11C-dLop), which is also a substrate
      for P-gp and thereby contaminates the radioactive signal in the brain. Should
      further demethylation of 11C-dLop occur, radiometabolites with low entry into the
      brain are generated. Therefore, we evaluated the ability of 11C-dLop to quantify
      the function of P-gp at the blood-brain barrier in monkeys. METHODS: Six monkeys
      underwent 12 PET scans of the brain, 5 at baseline and 7 after pharmacologic
      blockade of P-gp. A subset of monkeys also underwent PET scans with 15O-water to
      measure cerebral blood flow. To determine whether P-gp blockade affected
      peripheral distribution of 11C-dLop, we measured whole-body biodistribution in 4
      monkeys at baseline and after P-gp blockade. RESULTS: The concentration of 11C
      dLop in the brain was low under baseline conditions and increased 5-fold after P
      gp blockade. This increase was primarily caused by an increased rate of entry
      into the brain rather than a decreased rate of removal from the brain. With P-gp
      blockade, uptake of radioactivity among brain regions correlated linearly with
      blood flow, suggesting a high single-pass extraction. After correction for
      cerebral blood flow, the uptake of 11C-dLop was fairly uniform among brain
      regions, suggesting that the function of P-gp is fairly uniformly distributed in
      the brain. On whole-body imaging, P-gp blockade significantly affected
      distribution of radioactivity only to the brain and not to other visually
      identified source organs. The effective dose estimated for humans was
      approximately 9 microSv/MBq. CONCLUSION: PET with 11C-dLop can quantify P-gp
      function at the blood-brain barrier in monkeys. The single-pass extraction of 11C
      dLop is high and requires correction for blood flow to accurately measure the
      function of this efflux transporter. The low uptake at baseline and markedly
      increased uptake after P-gp blockade suggest that 11C-dLop will be useful to
      measure a wide range of P-gp functions at the blood-brain barrier in humans.

PMID- 19091891
TI  - Mayo Clinic approaches to meet United States Pharmacopeia <797> requirements for
      facility design and environmental controls of nuclear pharmacy.
AB  - According to the United States Pharmacopeia (USP) General Chapter <797> (USP
      <797>), "Pharmaceutical Compounding-Sterile Preparations," the compounding
      facility must be physically designed and environmentally controlled to minimize
      airborne contamination from contacting critical sites. The goal of the project
      was to evaluate the appropriateness and effectiveness of our approaches in
      meeting <797> requirements. METHODS: USP <797> standards, radiation safety
      concerns, and work-flow patterns were the focal points in our assessment of 4
      laboratories: 2 nuclear pharmacy laboratories that engage in preparing sterile
      (low-, medium-, and high-risk levels), nonsterile, or possible hazardous
      radioactive drugs and 2 other laboratories in which only low-risk-level
      preparations are involved. RESULTS: Each laboratory was constructed with a
      physically separated International Organization for Standardization Class 7
      anteroom and clean room to allow us to maintain an appropriate air quality, a
      consistent operation, and a desirable flexibility. An isolated area within the
      laboratory was designated for preparing nonsterile products. Higher air change
      per hour was used in the areas with higher traffic or smaller space. Lead-lined
      biological safety cabinets (BSCs) were segregated and used depending on the risk
      category of the preparations. In 1 laboratory, the exhaust flow for the BSC was
      too great, and a lead-lined compounding aseptic containment isolator (CACI) was
      installed. Air in the BSC and CACI was 100% exhausted to the atmosphere.
      99Mo/99mTc generators were placed in the negative-pressure clean room to ensure a
      more efficient operation and cleaner air environment. Clean-room equipment (i.e.,
      keyboards, printers, and telephones) was installed, and refrigerators or freezers
      and the central-processing unit of each computer were placed outside clean room.
      CONCLUSION: Our wide-range preparations of sterile, nonsterile, or potential
      hazardous radiopharmaceuticals, coupled with the limited space of each laboratory
      and existing antiquated mechanical systems, presented a challenge. Nevertheless,
      we successfully remodeled each nuclear pharmacy laboratory to meet USP <797>
      requirements for facility design and environmental controls.

PMID- 19091892
TI  - Repeatability of rest and hyperemic myocardial blood flow measurements with 82Rb
      dynamic PET.
AB  - The repeatability of rest and hyperemic myocardial blood flow (MBF) measurements
      using 82Rb PET has not been evaluated. The aim of this study was to investigate
      the short-term repeatability of such measurements. METHODS: Fifteen healthy
      volunteers underwent rest and pharmacologic stress 82Rb PET, repeated 60 min
      apart. RESULTS: There was no significant difference in repeated rest MBF (0.77+/
      0.25 vs. 0.82+/-0.25 mL/min/g, P=0.31; mean difference, 6.18%+/-12.22%) or
      repeated hyperemic MBF (3.35+/-1.37 vs. 3.39+/-1.37 mL/min/g, P=0.81; mean
      difference, 1.17%+/-13.64%). The repeatability coefficients were 0.19 mL/min/g
      for rest MBF and 0.92 mL/min/g for hyperemia. CONCLUSION: MBF using 82Rb is
      highly reproducible using a same-day short-term repeatability protocol. Serial
      MBF measurements with 82Rb PET should have the ability to quantify the acute
      effects of therapeutic interventions on MBF.

PMID- 19091893
TI  - Osteonecrosis of the jaw: more heat than light.

PMID- 19091894
TI  - Bone scintigraphy and SPECT/CT of bisphosphonate-induced osteonecrosis of the
      jaw.
AB  - Endovenous bisphosphonate therapy seems associated with osteonecrosis of the jaw.
      The aim of this study was to evaluate the additional diagnostic value of hybrid
      SPECT/CT in 99mTc-methylene diphosphonate 3-phase bone scintigraphy of
      osteonecrosis of the jaw in bisphosphonate-treated patients. METHODS: We studied
      15 patients (12 women and 3 men) with extraoral tumors affected by lytic bone
      metastases and multiple myeloma. All patients were previously treated with
      intravenous bisphosphonates (zoledronic acid) for 1-3 y, were negative for dental
      disease at clinical examination, and had suspected osteonecrosis of the jaw. All
      15 patients underwent panoramic x-ray orthopantomography, CT or MRI (or both),
      microbiologic examination, 3-phase bone scintigraphy, and SPECT/CT of the
      maxillary region. RESULTS: Three-phase bone-scintigraphy showed increased
      perfusion and an increased blood pool in 9 of 12 and 10 of 12 patients,
      respectively; at the metabolic phase, SPECT was positive in all patients and
      showed abnormal hyperactivity in the maxilla of 2 patients, in the mandible of 9
      patients, and in both the mandible and the maxilla of 4 patients. Hybrid SPECT/CT
      was of particular value in 8 of 15 patients, allowing discrimination of the
      osteonecrotic core from nearby hyperactivity due to viable bone. Whole-body
      scintigraphy showed remote and multiple metastases in all patients.
      Orthopantomography showed nonspecific bone rarefaction in all patients but was
      not able to aid diagnosis of osteonecrosis of the jaw. CT and MRI showed
      anomalies in all symptomatic patients: CT was helpful in evaluating both cortical
      and trabecular bone aspects, and MRI was able to detect soft-tissue involvement
      but not cortical bone destruction. CONCLUSION: In appropriately selected oncology
      patients treated with bisphosphonates, an increased uptake of 99mTc-methylene
      diphosphonate in maxillary bones may suggest probable osteonecrosis of the jaw.
      In such cases, SPECT/CT may be of value in increasing the diagnostic accuracy of
      bone scanning, providing a precise functional anatomic correlation for the
      definition of the extent of disease.

PMID- 19091896
TI  - Can delayed cortical transit identify those kidneys whose function is at risk?

PMID- 19091897
TI  - Validation of gated blood-pool SPECT regional left ventricular function
      measurements.
AB  - Blood-pool (BP)-gated SPECT should be able to detect regional left ventricular
      (LV) dysfunction, as the modality is fully 3-dimensional and capable of resolving
      all cardiac chambers. This study investigates the hypothesis that LV segments
      that have abnormal regional wall motion (WM) on a cardiac MRI scan also have
      abnormal BP regional ejection fraction (EF) as computed by fully automated
      quantitation (AQ) of BP data. METHODS: A total of 34 patients evaluated for
      coronary artery disease who underwent visual assessment of WM by review of BP
      cines and cardiac MRI evaluations were included in this retrospective
      investigation. Cardiac MRI values for these patients were compared with an
      institutional database of cardiac MRI values for an age-matched cohort of 10
      healthy volunteers. An AQ algorithm segmented the LV BPs on the BP tomograms and
      subdivided volumes into 17 subregions. Count-versus-time curves were fit to third
      order Fourier series for each LV subvolume to compute regional EFs. For cardiac
      MRI data, endocardial and epicardial drawings were performed manually for 60
      degrees samples of 11-13 short-axis tomograms spanning the entire heart, from
      which regional WM values were computed and rebinned into 17 conventional LV
      segments. RESULTS: Global EF ranged from 12% to 75% on AQ and from 14% to 75% on
      cardiac MRI (Pearson correlation coefficient=0.95, P<0.0001). Differences were
      not significant between BP AQ and cardiac MRI in identifying the 12 patients with
      a global EF less than 35% (McNemar difference, 3%; P=1.0) and the 19 patients
      with an EF less than 50% (difference, 3%; P=1.0). BP AQ was more accurate than
      was visual assessment for identifying LV segments with abnormal cardiac MRI WM
      (receiver-operating-characteristic areas, 88% vs. 80%, P<0.0001) and was more
      accurate for the left circumflex than for the left anterior descending coronary
      artery territories (95% vs. 86%, P=0.01). Differences were not significant
      between BP AQ and cardiac MRI WM for discriminating normal from abnormal LV
      segments (McNemar difference, 3.2%; P=0.14). CONCLUSION: AQ BP-gated SPECT
      assessment of regional and global LV WM agrees with independent cardiac MRI
      calculations and is superior to visual analysis for detecting regional WM
      abnormalities.

PMID- 19091898
TI  - Quantification of left ventricular volumes and ejection fraction in mice using
      PET, compared with MRI.
AB  - PET has become an important noninvasive imaging technique in cardiovascular
      research for the characterization of mouse models in vivo. This modality offers
      unique insight into biochemical changes on a molecular level, with excellent
      sensitivity. However, morphologic and functional changes may be of equal
      importance for a thorough assessment of left ventricular (LV) pathophysiology.
      Although echocardiography and MRI are widely considered the imaging techniques of
      choice for the assessment of these parameters, their use with PET considerably
      increases study complexity and decreases cost- and time-efficiency. In this
      study, a novel method for the additional quantification of LV volumes and
      ejection fraction (EF) from PET was evaluated using cardiac MRI as the reference
      method. METHODS: The radiolabeled glucose derivative 18F-FDG was injected into 33
      mice (6 mice with previous permanent occlusion of the left anterior descending
      artery [LAD], 15 mice with a temporary 30-min occlusion of the LAD, and 12 mice
      without previous surgery). 18F-FDG uptake within the LV myocardium was measured
      using a dedicated small-animal PET scanner. After we reconstructed the images
      into 16 electrocardiogram (ECG)-gated frames, we determined the LV cavity volumes
      in end-diastole (EDV) and end-systole (ESV) and the EF using a semiautomatic
      segmentation algorithm based on elastic surfaces. A 6.3-T cardiac MRI examination
      was performed in the same animals using an ECG-triggered and respiratory-gated
      multislice cine sequence. The MR images were segmented with a semiautomatic
      algorithm using commercially available software. RESULTS: Overall, measurements
      from PET agreed well with those obtained by MRI. Mean EDV and ESV were slightly
      overestimated by PET (86+/-43 microL and 44+/-42 microL), compared with MRI (73+/
      44 microL and 41+/-46 microL); mean (+/-SD) EF was similar (PET, 55+/-19 microL;
      MRI, 54+/-18 microL). Correlation between PET and MRI was excellent for EDV
      (0.97) and ESV (0.96) and good for EF (0.86). The slope of the regression line
      was nearly perfect for EDV (0.98) and EF (1.01) and slightly below 1 for ESV
      (0.90), indicating a good separation of abnormal and normal values with PET. The
      y-intercept was above zero for EDV (15 microL) and ESV (7 microL) and near to
      zero for EF (0.2%). CONCLUSION: The quantification of LV volumes and EF in mice
      with PET is both efficient and accurate. This method allows for combined
      molecular and functional imaging of the left ventricle within a single scan,
      obviating additional sophisticated MRI in many cases.

PMID- 19091899
TI  - Use of a novel Arg-Gly-Asp radioligand, 18F-AH111585, to determine changes in
      tumor vascularity after antitumor therapy.
AB  - Despite the recent development of various radiolabeled Arg-Gly-Asp (RGD) peptides
      for imaging the alphavbeta3 integrin receptor, relatively little attention has
      been focused on the ability of these radiotracers to monitor changes in tumor
      vascularity after antitumor therapies. This study describes the favorable in vivo
      kinetics and tumor-targeting properties of 18F-AH111585, a novel 18F-RGD peptide,
      and its ability to monitor tumor vascularity noninvasively. METHODS: Mice bearing
      Lewis lung carcinoma (LLC) tumors or Calu-6 non-small cell lung tumor xenografts
      were used for in vivo biodistribution and small-animal PET imaging studies. In
      addition, some animals were treated with either low-dose paclitaxel or the
      vascular endothelial growth factor receptor-2 tyrosine kinase inhibitor ZD4190.
      Tumor uptake of 18F-AH111585 and microvessel density were then assessed. RESULTS:
      Biodistribution of 18F-AH111585 demonstrated rapid clearance from the blood and
      key background organs and good tumor accumulation, with 1.5 percentage injected
      dose per gram (%ID/g) present at 2 h after injection in LLC tumors. Small-animal
      PET imaging of Calu-6 tumors allowed visualization of tumors above background
      tissue, with mean baseline uptake of 2.2 %ID/g. Paclitaxel therapy reduced the
      microvessel density in LLC tumor-bearing mice and resulted in significantly
      reduced 18F-AH111585 tumor uptake (P<0.05). ZD4190 therapy resulted in a
      significant (31.8%) decrease in 18F-AH111585 uptake in Calu-6 tumors, compared
      with the vehicle control-treated Calu-6 tumors, which had a 26.9% increase in 18F
      AH111585 uptake over the same period (P<0.01). CONCLUSION: 18F-AH111585 is a
      promising 18F-labeled RGD tracer that offers a new approach to noninvasively
      image tumor vasculature. This tracer may reveal important information in the
      assessment of the impact of antitumor therapies, in particular those that
      predominantly target tumor blood vessels.

PMID- 19091900
TI  - The significance of cardiac sympathetic nervous system abnormality in the long
      term prognosis of patients with a history of ventricular tachyarrhythmia.
AB  - Severe left ventricular dysfunction or cardiac sympathetic nervous system (SNS)
      abnormality predicts cardiac death in various heart diseases, including
      arrhythmogenic disorders. However, it is not clear whether SNS abnormality
      predicts sudden cardiac death during long-term follow-up in patients with a
      history of ventricular tachyarrhythmia. We hypothesized that SNS abnormality
      would be associated with recurrent ventricular arrhythmic events. METHODS: 123I
      metaiodobenzylguanidine (MIBG) scintigraphy was performed on 86 patients (mean
      age+/-SD, 46+/-19 y, 65.1% men) with a history of ventricular tachycardia or
      fibrillation. 123I-MIBG (111 MBq) was intravenously administered under resting
      conditions, and planar images were obtained 15 min and 4 h later (anterior view
      for 6 min; 512x512 matrices; zoom ratio, 1.0). SNS activity was assessed using
      the heart-to-mediastinum ratio on delayed imaging. RESULTS: During about 11 y of
      follow-up (mean+/-SD, 5.2+/-3.7 y), 3 patients (3.5%) had sudden cardiac death
      and 21 patients (24.4%) had sustained ventricular tachyarrhythmic events. SNS
      abnormality, defined as a heart-to-mediastinum ratio of less than 2.8, and left
      ventricular dysfunction, defined as a left ventricular ejection fraction of less
      than 50%, were associated with sudden cardiac death or recurrent ventricular
      tachyarrhythmic events (18/40 patients [45%] with SNS abnormality, vs. 6/46
      patients [13%] without, P=0.004; 9/15 patients [60%] with left ventricular
      dysfunction, vs. 15/71 patients [21.1%] without, P=0.008). After adjustment for
      potential confounding variables such as age, sex, coronary risk factors,
      medication use, history of structural heart disease, and left ventricular
      function, SNS abnormality was a powerful predictor of recurrent arrhythmic
      events, with a hazard ratio of 3.6 [95% confidence interval, 1.4-9.2, P=0.007]).
      Further, SNS abnormality had incremental and additive prognostic power in
      combination with left ventricular dysfunction, with an adjusted hazard ratio of
      4.4 [95% confidence interval, 1.9-9.9, P<0.0001]). CONCLUSION: SNS abnormality
      predicted recurrent ventricular tachyarrhythmic events during long-term follow
      up. 123I-MIBG scintigraphic evaluations for SNS abnormality may be an option for
      screening patients at high risk for sudden cardiac death.

PMID- 19091901
TI  - Does 18F-FDG PET/CT improve the detection of posttreatment recurrence of head and
      neck squamous cell carcinoma in patients negative for disease on clinical follow
      up?
AB  - Posttreatment surveillance for the recurrence of head and neck squamous cell
      carcinoma (HNSCC) is a diagnostic challenge. Tissue distortion from radiation and
      surgery can obscure early detection of recurrence by conventional follow-up
      approaches such as physical examination, CT, and MRI. Several studies have shown
      that 18F-FDG PET may be an effective technique for the detection of persistent,
      recurrent, and distant metastatic HNSCC after treatment. The aim of this
      prospective study was to determine the benefits of hybrid 18F-FDG PET/CT in
      detecting a subclinical locoregional recurrence of HNSCC and distant metastases.
      The study patients were considered cured of HNSCC on the basis of 12 mo of
      negative findings on conventional follow-up. We also assessed the diagnostic
      accuracy of 18F-FDG PET/CT in these patients. METHODS: Ninety-one patients cured
      of HNSCC without any clinical evidence of recurrence were included. Whole-body
      18F-FDG PET/CT examination was performed 11.6+/-4.4 mo after the end of the
      treatment. The gold standard was histopathology or 6 mo of imaging follow-up.
      RESULTS: The whole-body 18F-FDG PET/CT examinations had negative results in 52
      patients and positive results in 39. Nine of these patients who exhibited
      abnormal 18F-FDG uptake in the head and neck area did not have recurrent HNSCC
      (false-positive). Thirty had proven recurrence. The sensitivity and specificity
      of 18F-FDG PET/CT in this study for the diagnosis of HNSCC recurrence were 100%
      (30/30) and 85% (52/61), respectively. The positive predictive value was 77%
      (30/39). The negative predictive value was 100% (52/52). The overall accuracy was
      90% (82/91). CONCLUSION: The results of our study confirm the high effectiveness
      of 18F-FDG PET/CT in the assessment of HNSCC recurrence and suggest that 18F-FDG
      PET/CT is more accurate than conventional follow-up physical examination alone in
      the assessment of recurrence after previous curative treatment for HNSCC and
      could be proposed systematically at 12 mo of the usual follow-up.

PMID- 19091902
TI  - Accuracy of 3-dimensional reconstruction algorithms for the high-resolution
      research tomograph.
AB  - The high-resolution research tomograph (HRRT) is a dedicated human brain PET
      scanner. At present, iterative reconstruction methods are preferred for
      reconstructing HRRT studies. However, these iterative reconstruction algorithms
      show bias in short-duration frames. New algorithms such as the shifted Poisson
      ordered-subsets expectation maximization (SP-OSEM) and ordered-subsets weighted
      least squares (OSWLS) showed promising results in bias reduction, compared with
      the recommended ordinary Poisson OSEM (OP-OSEM). The goal of this study was to
      evaluate quantitative accuracy of these iterative reconstruction algorithms,
      compared with 3-dimensional filtered backprojection (3D-FBP). METHODS: The 3
      above-mentioned 3D iterative reconstruction methods were implemented for the
      HRRT. To evaluate the various 3D iterative reconstruction techniques
      quantitatively, several phantom studies and a human brain study (n=5) were
      performed. RESULTS: OSWLS showed a low and almost linearly increasing coefficient
      of variation (SD over average activity concentration), with decreasing noise
      equivalent count rates. In decay studies, OSWLS showed good agreement with the 3D
      FBP gray matter (GM)-to-white matter (WM) contrast ratio (<4%), and OP-OSEM and
      SP-OSEM showed agreement within 6% and 7%, respectively. For various frame
      durations, both SP-OSEM and OP-OSEM showed the fewest errors in GM-to-WM contrast
      ratios, varying 75% between different noise-equivalent count rates; this
      variability was much higher for other iterative methods (>92%). 3D-FBP showed the
      least variability (34%). Visually, OSWLS hardly showed any artifacts in
      parametric images and showed good agreement with 3D-FBP data for parametric
      images, especially in the case of reference-tissue kinetic methods (slope, 1.02;
      Pearson correlation coefficient, 0.99). CONCLUSION: OP-OSEM, SP-OSEM, and OSWLS
      showed good performance for phantom studies. In addition, OSWLS showed better
      results for parametric analysis of clinical studies and is therefore recommended
      for quantitative HRRT brain PET studies.

PMID- 19091903
TI  - 18F-FDG PET/CT for monitoring the response of lymphoma to radioimmunotherapy.
AB  - We retrospectively evaluated 18F-FDG PET/CT for monitoring the response of non
      Hodgkin's lymphoma to radioimmunotherapy. METHODS: A total of 33 clinical
      patients received 131I-tositumomab (n=23) or 90Y-ibritumomab tiuxetan (n=10) and
      underwent 18F-FDG PET/CT scans before radioimmunotherapy and at 12 wk after
      radioimmunotherapy. A third scan was performed on 13 patients at 24 wk after
      radioimmunotherapy, 12 of whom did not receive interval therapy. Tumor metabolic
      activity was assessed before and after radioimmunotherapy visually and
      quantitatively by lean maximum standardized uptake value (SUVlean max). Response
      was assessed by the International Workshop Criteria (IWC) and Revised IWC, which
      includes 18F-FDG PET (IWC-PET). RESULTS: Mean SUVlean max decreased from baseline
      in 244 target lesions 12 wk after radioimmunotherapy (from 6.51+/-4.05 to 3.94+/
      4.41; P<0.01), regardless of response at 12 wk after radioimmunotherapy
      (P<or=0.02). After radioimmunotherapy, SUVlean max was lower for responders than
      for nonresponders (P<or=0.01). Median percentage change in SUVlean max of target
      lesions per patient was -51% (-95% to 97%). No significant difference in decline
      in SUVlean max between patients who received 131I-tositumomab and those who
      received 90Y-ibritumomab tiuxetan was demonstrated (-31%+/-51% vs. -47%+/-46%;
      P=0.38). Patients with greater than a 52% decline in SUVlean max tended toward
      longer survival (P=0.09) than those with lesser declines. The 12-wk overall
      response rate to radioimmunotherapy based on IWC was 42% (14/33); complete
      response rate was 15% (5/33). Eleven of 12 patients with progression at 12 wk had
      new disease sites, and in 4 patients, new disease sites were the only sites of
      progression. Of 108 lesions evaluated at 12 and 24 wk after radioimmunotherapy,
      49 resolved at 12 wk and remained resolved at 24 wk, 17 gradually declined in SUV
      over 24 wk, and 37 initially decreased at 12 wk but increased at 24 wk. PET
      showed disease progression at 24 wk in 10 of 13 patients; 7 patients had new
      lesions and 1 was reclassified from partial response to complete response.
      CONCLUSION: In non-Hodgkin's lymphoma, 18F-FDG uptake in tumors typically drops
      significantly after radioimmunotherapy. A continued decline in tumor SUVlean max
      between 12 and 24 wk without additional therapy can occur, suggesting a need for
      delayed-response assessment. In patients who progress after radioimmunotherapy,
      new sites of disease commonly develop, rather than recurrence or progression at
      previous disease sites. Large declines in 18F-FDG uptake tend to be seen in those
      with the longest progression-free survival.

PMID- 19091904
TI  - Increased metabolic activity of indolent liver metastases after resection of a
      primary colorectal tumor.

PMID- 19091905
TI  - Assessment of human biodistribution and dosimetry of 4-fluoro-11beta-methoxy
      16alpha-18F-fluoroestradiol using serial whole-body PET/CT.
AB  - 4-Fluoro-11beta-methoxy-16alpha-18F-fluoroestradiol (4FMFES) is a newly developed
      radiolabeled estradiol analog for PET imaging of estrogen receptors (ERs) that
      shows improved target-to-background ratios, compared with 16alpha-18F
      fluoroestradiol (FES), in small-animal models. The aim of this study was to
      assess the biodistribution, dosimetry, and safety of 4FMFES in healthy women.
      METHODS: Ten healthy subjects (6 pre- and 4 postmenopausal women) who had fasted
      were injected with 66-201 MBq of 4FMFES at a high effective specific activity
      (median, 251 GBq/micromol). During a 2-h period, each subject underwent 4 serial
      rapid PET acquisitions and 2 low-dose CT acquisitions on a PET/CT camera. Volumes
      of interest were drawn over source organs for each PET acquisition, allowing the
      calculation of time-activity curves, residence times, and radiation dosimetry
      estimates. Serial blood samples were obtained to measure blood and plasma
      activity clearance. 4FMFES safety was assessed by blood and urine analyses and
      vital-sign monitoring. RESULTS: A 4FMFES injection was well tolerated in all
      subjects. The liver showed high uptake, and the hepatobiliary excretion was
      massive. Little urinary excretion occurred. Uterus uptake was visualized in all
      subjects and remained relatively constant over time (maximum and mean
      standardized uptake values at 60 min were 5.34+/-3.32 and 2.68+/-1.89,
      respectively). Background activity was low and decreased over time, resulting in
      an increasing uterus-to-background ratio (12.1+/-2.2 at 60 min). The critical
      organ was the gallbladder (0.80+/-0.51 mGy/MBq), followed by the upper large
      intestine (0.13+/-0.04 mGy/MBq), small intestine (0.12+/-0.04 mGy/MBq), and liver
      (0095+/-0.019 mGy/MBq). For a typical 4FMFES dose of 185 MBq, the effective dose
      was calculated at 4.82+/-0.70 mSv. CONCLUSION: 4FMFES is considered safe for use
      in humans, and its effective dose remains well within acceptable limits. The
      absorbed dose to the gallbladder was relatively high and could potentially be
      reduced by injecting 4FMFES in patients who had not fasted. 4FMFES showed a
      significant, potentially estrogen receptor-mediated uterus uptake in both pre-
      and postmenopausal subjects.

PMID- 19091906
TI  - Disparity between in vivo EGFR expression and 89Zr-labeled cetuximab uptake
      assessed with PET.
AB  - The epidermal growth factor receptor (EGFR) is highly expressed in a significant
      number of human malignancies, and its expression is associated with tumor
      aggressiveness and overall treatment resistance. The monoclonal antibody
      cetuximab is increasingly used in clinical settings as a treatment modality in
      combination with more conventional therapies, such as radio- and chemotherapy.
      Currently, little is known about tumor-specific uptake and overall
      pharmacokinetics. Noninvasive quantification of cetuximab uptake could provide
      important diagnostic information for patient selection and therapy evaluation. To
      this end, we have developed and validated a novel probe using cetuximab labeled
      with the long-lived positron emitter 89Zr for PET imaging. METHODS: Tumor cell
      lines with varying EGFR expression levels were used for in vivo tumor imaging
      experiments. PET with 89Zr-labeled cetuximab (3.75+/-0.14 MBq) was performed on
      tumor-bearing NMRI-nu mice at multiple time points after injection (ranging from
      1 to 120 h) and quantified by drawing regions of interest on selected tissues.
      Uptake was compared by biodistribution gamma-counting, and ex vivo EGFR
      expression levels were quantified using Western blot analysis. RESULTS: Uptake of
      89Zr-labeled cetuximab was demonstrated in the EGFR-positive tumors. However, the
      EGFR levels measured in vivo did not correlate with the relative signal obtained
      by PET. Tumor-to-blood ratios were significantly higher in the cell lines with
      intermediate (compared with the high) EGFR expression starting from 24 h after
      injection. Normal tissue uptake was unaffected by the different tumor types. Ex
      vivo gamma-counting experiments confirmed the observed in vivo PET results. A
      similar disparity was found between 89Zr-labeled cetuximab tumor uptake and in
      vivo EGFR expression levels as demonstrated by Western blotting. CONCLUSION: The
      89Zr-labeled cetuximab imaging probe is a promising tool for noninvasive
      evaluation of cetuximab uptake. Our results demonstrate a disparity between in
      vivo EGFR expression levels and cetuximab uptake. In a general sense, the results
      indicate a disparity between antibody uptake and expression levels of a biologic
      target in a tumor, suggesting that additional pharmacokinetic or pharmacodynamic
      mechanisms influence tumor delivery of this therapy. These additional mechanisms
      may explain why receptor expression levels alone are not sufficient to predict
      patient response.

PMID- 19091908
TI  - Histamine induces postprandial tachycardia through a direct effect on cardiac H2
      receptors in pythons.
AB  - The intrinsic heart rate of most vertebrates studied, including humans, is
      elevated during digestion, suggesting that a nonadrenergic-noncholinergic factor
      contributes to the postprandial tachycardia. The regulating factor, however,
      remains elusive and difficult to identify. Pythons can ingest very large meals,
      and digestion is associated with a marked rise in metabolism that is sustained
      for several days. The metabolic rise causes more than a doubling of heart rate
      and a fourfold rise in cardiac output. This makes the python an interesting model
      to investigate the postprandial tachycardia. We measured blood pressure and heart
      rate in fasting Python regius, and at 24 and 48 h after ingestion of a meal
      amounting to 25% of body wt. Digestion caused heart rate to increase from 25 to
      56 min, whereas blood pressure was unchanged. The postprandial rise in heart rate
      was partially due to a doubling of intrinsic heart rate. The H(2)-antagonist did
      not affect heart rate of fasting snakes but decreased heart rate by 15-20 min at
      24 h into digestion, whereas it had no effects at 48 h. Thus, the histaminergic
      tone on the heart rose from none to 30% at 24 h but vanished after 48 h. In
      anesthetized snakes, histamine caused a systemic vasodilatation and a marked
      increase in heart rate and cardiac output mediated through a direct effect on
      H(2)- receptors. Our study strongly indicates that histamine regulates heart rate
      during the initial phase of digestion in pythons. This study describes a novel
      regulation of the vertebrate heart.

PMID- 19091910
TI  - Structural, gene expression, and functional analysis of the fugu (Takifugu
      rubripes) insulin-like growth factor binding protein-4 gene.
AB  - The insulin-like growth factor (IGF) signaling pathway is a conserved pathway
      that regulates animal development, growth, metabolism, reproduction, and aging.
      The biological actions of IGFs are modulated by IGF-binding proteins (IGFBPs).
      Although the structure and function of fish IGFBP-1, -2, -3, and -5 have been
      elucidated, there is currently no report on the full-length structure of a fish
      IGFBP-4 nor its biological action. In this study, we cloned and characterized the
      IGFBP-4 gene from fugu. Sequence comparison, phylogenetic, and synteny analyses
      indicate that its chromosomal location, gene, and protein structure are similar
      to its mammalian orthologs. Fugu IGFBP-4 mRNA was easily detectable in all adult
      tissues examined with the exception of spleen. Older animals tended to have
      higher levels of IGFBP-4 mRNA in the muscle and eyes compared with younger
      animals. Starvation resulted in significant increases in IGFBP-4 mRNA abundance
      in the muscle, liver, gallbladder, and brain. Overexpression of fugu and human
      IGFBP-4 in zebrafish embryos caused a significant decrease in body size and
      somite number, suggesting that fugu IGFBP-4 inhibits growth and development,
      possibly by binding to IGFs and inhibiting their binding to the IGF receptors.
      These results provide new information about the structural and functional
      conservation, expression patterns, and physiological regulation of the IGFBP-4
      gene in a teleost fish.

PMID- 19091909
TI  - Altered central TRPV4 expression and lipid raft association related to
      inappropriate vasopressin secretion in cirrhotic rats.
AB  - Inappropriate vasopressin (AVP) release causes dilutional hyponatremia in many
      pathophysiological states such as cirrhosis. The central molecular mechanisms
      that mediate inappropriate AVP release are unknown. We tested the hypothesis that
      changes in the expression or trafficking of TRPV4 in the central nervous system
      may contribute to inappropriate AVP release in the bile duct ligation (BDL) model
      of cirrhosis in the rat. Four weeks after surgery, BDL rats demonstrated
      significantly increased plasma vasopressin and plasma renin activity (PRA),
      hypervolemia, and decreased plasma osmolality. These effects were blocked by
      providing BDL rats with 2% saline to drink for 15 days. TRPV4 protein expression
      was significantly increased in brain punches from BDL rats containing the
      supraoptic nucleus (SON) of the hypothalamus (100% +/- 11 to 157% +/- 4.8), and
      this effect was blocked in BDL rats given saline. Immunohistochemistry
      demonstrated a significant increase in TRPV4-positive cells and the percentage of
      AVP neurons that also were TRPV4-positive in the SON of BDL rats. In the
      hypothalamus of BDL rats, TRPV4 lipid raft association increased compared with
      sham (from 100% +/- 2.1 to 326.1% +/- 16). This effect was significantly
      attenuated in BDL rats given 2% saline to drink (174% +/- 11). In the brain stem,
      TRPV4 lipid raft association was reduced by BDL and inversely related to plasma
      AVP and PRA. We speculate that changes in TRPV4 expression and
      compartmentalization within lipid rafts could contribute to a feed-forward
      mechanism related to AVP release in cirrhosis.

PMID- 19091911
TI  - T1R3 taste receptor is critical for sucrose but not Polycose taste.
AB  - In addition to their well-known preference for sugars, mice and rats avidly
      consume starch-derived glucose polymers (e.g., Polycose). T1R3 is a component of
      the mammalian sweet taste receptor that mediates the preference for sugars and
      artificial sweeteners in mammals. We examined the role of the T1R3 receptor in
      the ingestive response of mice to Polycose and sucrose. In 60-s two-bottle tests,
      knockout (KO) mice preferred Polycose solutions (4-32%) to water, although their
      overall preference was lower than WT mice (82% vs. 94%). KO mice also preferred
      Polycose (0.5-32%) in 24-h two-bottle tests, although less so than WT mice at
      dilute concentrations (0.5-4%). In contrast, KO mice failed to prefer sucrose to
      water in 60-s tests. In 24-h tests, KO mice were indifferent to 0.5-8% sucrose,
      but preferred 16-32% sucrose; this latter result may reflect the post-oral
      effects of sucrose. Overall sucrose preference and intake were substantially less
      in KO mice than WT mice. However, when retested with 0.5-32% sucrose solutions,
      the KO mice preferred all sucrose concentrations, although they drank less sugar
      than WT mice. The experience-induced sucrose preference is attributed to a post
      oral conditioned preference for the T1R3-independent orosensory features of the
      sugar solutions (odor, texture, T1R2-mediated taste). Chorda tympani nerve
      recordings revealed virtually no response to sucrose in KO mice, but a near
      normal response to Polycose. These results indicate that the T1R3 receptor plays
      a critical role in the taste-mediated response to sucrose but not Polycose.

PMID- 19091912
TI  - Effect of menopause on the chemical control of breathing and its relationship
      with acid-base status.
AB  - This study examined the role of alterations in the chemoreflex control of
      breathing, acid-base balance, and their interaction in postmenopausal ventilatory
      adaptations. A modified iso-oxic hyperoxic and hypoxic CO(2)-rebreathing
      procedure was employed to evaluate central and peripheral chemoreflex drives to
      breathe, respectively, in 15 healthy postmenopausal and 20 premenopausal women of
      similar age. Arterialized venous blood samples were collected at rest for the
      estimation of arterial Pco(2) (Pa(CO(2))) and H(+) concentration ([H(+)]), plasma
      strong ion difference ([SID]) and total weak acid ([A](tot)) concentrations, and
      serum progesterone ([P(4)]) and 17beta-estradiol ([E(2)]) concentrations. In post
      compared with premenopausal women, Pa(CO(2)), [SID], and the central chemoreflex
      ventilatory recruitment threshold for Pco(2) (VRTco(2)) were higher, whereas
      [P(4)] and [E(2)] were lower (all P < 0.05), with no significant change in
      central or peripheral chemoreflex sensitivity, peripheral chemoreflex VRTco(2),
      and [A](tot). The acidifying effect of an increased Pa(CO(2)) was offset by the
      alkalizing effect of an increased [SID], such that [H(+)] was preserved in post-
      compared with premenopausal women. Pa(CO(2)) correlated positively with the
      central chemoreflex VRTco(2) (r = 0.67, P < 0.01), which in turn correlated
      positively with [SID] (r = 0.53, P < 0.01) within the pooled data. In conclusion,
      the relative alveolar hypoventilation and attendant arterial hypercapnia in
      healthy post- compared with premenopausal women could be explained, in part, by
      the interaction of 1) reduced central, but not peripheral, chemoreflex VRTco(2),
      2) increased [SID], and 3) reduced circulating female sex steroid hormone
      concentrations.

PMID- 19091913
TI  - Hypercapnic vs. hypoxic control of cardiovascular, cardiovagal, and sympathetic
      function.
AB  - We compared the integrated cardiovascular and autonomic responses to hypercapnia
      and hypoxia to test the hypothesis that these stimuli differentially affect
      muscle sympathetic nerve activity (MSNA) discharge patterns and cardiovagal and
      sympathetic baroreflex function in a manner related to ventilatory chemoreflex
      sensitivity. Six males and six females underwent 5 min of hypoxia (end-tidal Po2
      = 45 Torr) and 5 min of hypercapnia (end-tidal Pco2 = +8 Torr from baseline),
      causing similar ventilatory responses. A downward right shift in cardiovagal set
      point was observed during both conditions, which was strongly related to the
      change in inspiratory time (Ti) from baseline to hypercapnia (r2 = 0.67, P =
      0.007) and hypoxia (r2 = 0.79, P < 0.001). Cardiovagal baroreflex gain was
      decreased during hypoxia (20.1 +/- 6.9 vs. 8.9 +/- 5.1 ms/mmHg, P < 0.001) but
      not hypercapnia (26.7 +/- 12.7 vs. 23.0 +/- 9.1 ms/mmHg). Both hypoxia and
      hypercapnia increased MSNA burst amplitude, whereas hypoxia, but not hypercapnia,
      also increased in MSNA burst frequency (21 +/- 9 vs. 28 +/- 7 bursts/min, P =
      0.03) and total MSNA (4.56 +/- 3.07 vs. 7.37 +/- 3.26 mV/min, P = 0.002).
      However, neither hypercapnia nor hypoxia affected sympathetic burst probability
      or baroreflex gain. Hypoxia also caused a greater reduction in total peripheral
      resistance (P = 0.04), a greater increase in heart rate (P = 0.002), and a trend
      for a greater cardiac output response (P = 0.06) compared with hypercapnia.
      Nonetheless, central venous pressure remained unchanged during either condition.
      These results suggest that hypercapnia and hypoxia exert differential effects on
      cardiovagal, but not sympathetic, baroreflex gain and set point in a manner not
      related to ventilatory chemoreflex sensitivity. Furthermore, the data suggest
      that the individual's respiratory pattern to hypoxia or hypercapnia, as reflected
      in the inspiratory time, was a strong determinant of cardiovagal baroreflex set-
      point rather than the total ventilatory chemoreflex gain per se.

PMID- 19091914
TI  - Hypocapnia increases the prevalence of hypoxia-induced augmented breaths.
AB  - Augmented breaths promote respiratory instability and have been implicated in
      triggering periods of sleep-disordered breathing. Since respiratory instability
      is well known to be exacerbated by hypocapnia, we asked whether one of the
      destabilizing effects of hypocapnia might be related to an increased prevalence
      of augmented breaths. With this question in mind, we first sought to determine
      whether hypoxia-induced augmented breaths are more prevalent when hypocapnia is
      also present. To do this, we studied the breath-by-breath ventilatory responses
      of a group of freely behaving adult rats in a variety of different respiratory
      background conditions. We found that the prevalence of augmented breaths was
      dramatically increased during hypocapnic-hypoxia compared with room air
      conditions. When hypocapnia was prevented during exposure to hypoxia by adding 5%
      CO2 to the inspired air, the rate of occurrence of augmented breaths was no
      greater than that observed in room air. The addition of CO2 alone to room air had
      no effect on the prevalence of augmented breaths. We conclude that in
      spontaneously breathing rats, hypoxia promotes the generation of augmented
      breaths, but only in poikilocapnic conditions, where hypocapnia develops. Our
      results, therefore, reveal a means by which CO2 exerts a stabilizing influence on
      breathing, which may be of particular relevance during sleep in conditions
      commonly associated with respiratory instability.

PMID- 19091915
TI  - Leptin resistance: a prediposing factor for diet-induced obesity.
AB  - Obesity is a resilient and complex chronic disease. One potential causative
      factor in the obesity syndrome is leptin resistance. Leptin behaves as a potent
      anorexic and energy-enhancing hormone in most young or lean animals, but its
      effects are diminished or lacking in the obese state associated with a normal
      genetic background. Emerging evidence suggests that leptin resistance predisposes
      the animal to exacerbated diet-induced obesity (DIO). Elevation of central leptin
      in young, lean rats induces a leptin resistance that precludes obesity on a chow
      diet but accelerates high-fat (HF)-induced obesity. Similarly, chronic dietary
      fructose consumption evokes a leptin resistance that causes obesity only upon HF
      exposure. Inherent central leptin insensitivity also contributes to dietary
      weight gain in certain obesity-prone rats. Conversely, aged, leptin-resistant
      animals are obese with continuous chow feeding and demonstrate aggravated obesity
      when challenged with an HF diet. Additionally, a submaximal central blockade with
      a leptin antagonist leads to obesity on both chow and HF diets, as is the case in
      rodents with leptin receptor deficiency of genetic origin. Despite the
      differences in the incidence of obesity on a chow diet, all of these forms of
      leptin resistance predispose rodents to aggravated HF-mediated obesity. Moreover,
      once leptin resistance takes hold, it aggravates DIO, and the leptin resistance
      and obesity compound one another, promoting a vicious cycle of escalating weight
      gain.

PMID- 19091916
TI  - Changes in the limb kinematics and walking-distance estimation after shank
      elongation: evidence for a locomotor body schema?
AB  - When walking, step length provides critical information on traveled distance
      along the ongoing path [corrected] Little is known on the role that knowledge
      about body dimensions plays within this process. Here we directly addressed this
      question by evaluating whether changes in body proportions interfere with
      computation of traveled distance for targets located outside the reaching space.
      We studied locomotion and distance estimation in an achondroplastic child (ACH,
      11 yr) before and after surgical elongation of the shank segments of both lower
      limbs and in healthy adults walking on stilts, designed to mimic shank-segment
      elongation. Kinematic analysis of gait revealed that dynamic coupling of the
      thigh, shank, and foot segments changed substantially as a result of elongation.
      Step length remained unvaried, in spite of the significant increase in total limb
      length ( approximately 1.5-fold). These relatively shorter strides resulted from
      smaller oscillations of the shank segment, as would be predicted by proportional
      increments in limb size and not by asymmetrical segmental increment as in the
      present case (length of thighs was not modified). Distance estimation was
      measured by walking with eyes closed toward a memorized target. Before surgery,
      the behavior of ACH was comparable to that of typically developing participants.
      In contrast, following shank elongation, the ACH walked significantly shorter
      distances when aiming at the same targets. Comparable changes in limb kinematics,
      stride length, and estimation of traveled distance were found in adults wearing
      on stilts, suggesting that path integration errors in both cases were related to
      alterations in the intersegmental coordination of the walking limbs. The results
      are consistent with a dynamic locomotor body schema used for controlling step
      length and path estimation, based on inherent relationships between gait
      parameters and body proportions.

PMID- 19091917
TI  - Efferent-mediated responses in vestibular nerve afferents of the alert macaque.
AB  - The peripheral vestibular organs have long been known to receive a bilateral
      efferent innervation from the brain stem. However, the functional role of the
      efferent vestibular system has remained elusive. In this study, we investigated
      efferent-mediated responses in vestibular afferents of alert behaving primates
      (macaque monkey). We found that efferent-mediated rotational responses could be
      obtained from vestibular nerve fibers innervating the semicircular canals after
      conventional afferent responses were nulled by placing the corresponding canal
      plane orthogonal to the plane of motion. Responses were type III, i.e.,
      excitatory for rotational velocity trapezoids (peak velocity, 320 degrees/s) in
      both directions of rotation, consistent with those previously reported in the
      decerebrate chinchilla. Responses consisted of both fast and slow components and
      were larger in irregular (approximately 10 spikes/s) than in regular afferents
      (approximately 2 spikes/s). Following unilateral labyrinthectomy (UL) on the side
      opposite the recording site, similar responses were obtained. To confirm the
      vestibular source of the efferent-mediated responses, the ipsilateral horizontal
      and posterior canals were plugged following the UL. Responses to high-velocity
      rotations were drastically reduced when the superior canal (SC), the only intact
      canal, was in its null position, compared with when the SC was pitched 50 degrees
      upward from the null position. Our findings show that vestibular afferents in
      alert primates show efferent-mediated responses that are related to the discharge
      regularity of the afferent, are of vestibular origin, and can be the result of
      both afferent excitation and inhibition.

PMID- 19091918
TI  - Integration of broadband conductance input in rat somatosensory cortical
      inhibitory interneurons: an inhibition-controlled switch between intrinsic and
      input-driven spiking in fast-spiking cells.
AB  - Quantitative understanding of the dynamics of particular cell types when
      responding to complex, natural inputs is an important prerequisite for
      understanding the operation of the cortical network. Different types of
      inhibitory neurons are connected by electrical synapses to nearby neurons of the
      same type, enabling the formation of synchronized assemblies of neurons with
      distinct dynamical behaviors. Under what conditions is spike timing in such cells
      determined by their intrinsic dynamics and when is it driven by the timing of
      external input? In this study, we have addressed this question using a systematic
      approach to characterizing the input-output relationships of three types of
      cortical interneurons (fast spiking [FS], low-threshold spiking [LTS], and
      nonpyramidal regular-spiking [NPRS] cells) in the rat somatosensory cortex,
      during fluctuating conductance input designed to mimic natural complex activity.
      We measured the shape of average conductance input trajectories preceding spikes
      and fitted a two-component linear model of neuronal responses, which included an
      autoregressive term from its own output, to gain insight into the input-output
      relationships of neurons. This clearly separated the contributions of stimulus
      and discharge history, in a cell-type dependent manner. Unlike LTS and NPRS
      cells, FS cells showed a remarkable switch in dynamics, from intrinsically driven
      spike timing to input-fluctuation-controlled spike timing, with the addition of
      even a small amount of inhibitory conductance. Such a switch could play a pivotal
      role in the function of FS cells in organizing coherent gamma oscillations in the
      local cortical network. Using both pharmacological perturbations and modeling, we
      show how this property is a consequence of the particular complement of voltage
      dependent conductances in these cells.

PMID- 19091919
TI  - Relation of locus coeruleus neurons in monkeys to Pavlovian and operant
      behaviors.
AB  - Noradrenaline is released throughout the forebrain from locus coeruleus (LC)
      projections in close temporal proximity to emotional and goal-directed events. To
      examine interactive influences of these processes on LC neuronal activity, we
      used a task where Pavlovian and operant processes vary and can be easily
      identified. We recorded 69 single LC neurons from two monkeys performing a task
      where cues indicate the progression through schedules of one, two, or three
      operant trials. Pavlovian responses and phasic LC activations occur following the
      appearance of conditioned visual cues (54/69 neurons), especially those at the
      beginning of new schedules, whether the current trial will be rewarded (single
      trial schedule) or not (2 or 3 trial schedules), and after visual imperative
      signals eliciting the operant response (64/69 neurons), whether the current trial
      will be rewarded or not. The modulation of LC responses seems to be relatively
      independent of attention or motivation, because the responses do not covary with
      operant performance in the task. The magnitude of LC responses across the
      schedules varied in close relation to the intensity of Pavlovian behavior but
      these responses were also modulated by operant processes. Our conclusion is that
      LC activation occurs when task-relevant stimuli evoke a conditioned instinctive
      (Pavlovian) response, with the strength of the activation also being modulated by
      goal-directed processes. Thus locus coeruleus neurons broadcast information about
      stimulus-elicited primitive and goal-directed behaviors to forebrain structures
      important for executive functions and emotions.

PMID- 19091920
TI  - Activity-dependent plasticity improves M1 motor representation and corticospinal
      tract connectivity.
AB  - Motor cortex (M1) activity between postnatal weeks 5 and 7 is essential for
      normal development of the corticospinal tract (CST) and visually guided
      movements. Unilateral reversible inactivation of M1, by intracortical muscimol
      infusion, during this period permanently impairs development of the normal
      dorsoventral distribution of CST terminations and visually guided motor skills.
      These impairments are abrogated if this M1 inactivation is followed by
      inactivation of the contralateral, initially active M1, from weeks 7 to 11
      (termed alternate inactivation). This later period is when the M1 motor
      representation normally develops. The purpose of this study was to determine the
      effects of alternate inactivation on the motor representation of the initially
      inactivated M1. We used intracortical microstimulation to map the left M1 1 to 2
      mo after the end of left M1 muscimol infusion. We compared representations in the
      unilateral inactivation and alternate inactivation groups. Alternate inactivation
      converted the sparse proximal M1 motor representation produced by unilateral
      inactivation to a complete and high-resolution proximal-distal representation.
      The motor map was restored by week 11, the same age that our present and prior
      studies demonstrated that alternate inactivation restored CST spinal
      connectivity. Thus M1 motor map developmental plasticity closely parallels
      plasticity of CST spinal terminations. After alternate inactivation reestablished
      CST connections and the motor map, an additional 3 wk was required for motor
      skill recovery. Since motor map recovery preceded behavioral recovery, our
      findings suggest that the representation is necessary for recovering motor
      skills, but additional time, or experience, is needed to learn to take advantage
      of the restored CST connections and motor map.

PMID- 19091921
TI  - High-resolution three-dimensional extracellular recording of neuronal activity
      with microfabricated electrode arrays.
AB  - Microelectrode array recordings of neuronal activity present significant
      opportunities for studying the brain with single-cell and spike-time precision.
      However, challenges in device manufacturing constrain dense multisite recordings
      to two spatial dimensions, whereas access to the three-dimensional (3D) structure
      of many brain regions appears to remain a challenge. To overcome this limitation,
      we present two novel recording modalities of silicon-based devices aimed at
      establishing 3D functionality. First, we fabricated a dual-side electrode array
      by patterning recording sites on both the front and back of an implantable
      microstructure. We found that the majority of single-unit spikes could not be
      simultaneously detected from both sides, suggesting that in addition to providing
      higher spatial resolution measurements than that of single-side devices, dual
      side arrays also lead to increased recording yield. Second, we obtained
      recordings along three principal directions with a multilayer array and
      demonstrated 3D spike source localization within the enclosed measurement space.
      The large-scale integration of such dual-side and multilayer arrays is expected
      to provide massively parallel recording capabilities in the brain.

PMID- 19091922
TI  - Behavioral evidence of separate adaptation mechanisms controlling saccade
      amplitude lengthening and shortening.
AB  - The accuracy of saccadic eye movements is maintained over the long term by
      adaptation mechanisms that decrease or increase saccade amplitude. It is still
      unknown whether these opposite adaptive changes rely on common mechanisms. Here,
      a double-step target paradigm was used to adaptively decrease (backward second
      target step) or increase (forward step) the amplitude of reactive saccades in one
      direction only. To test which sensorimotor transformation stages are subjected to
      these adaptive changes, we measured their transfer to antisaccades in which
      sensory and motor vectors are spatially dissociated. In the backward adaptation
      condition, all subjects showed a significant amplitude decrease for adapted
      prosaccades and a significant transfer of adaptation to antisaccades performed in
      the adapted direction, but not to oppositely directed antisaccades elicited by a
      target jump in the adapted direction. In the forward adaptation condition, only
      14 of 19 subjects showed a significant amplitude increase for prosaccades and no
      significant adaptation transfer to antisaccades was detected in either the
      adapted or nonadapted direction. These findings suggest that, whereas the
      level(s) of forward adaptation cannot be resolved, the mechanisms involved in
      backward adaptation of reactive saccades take place at a sensorimotor level
      downstream from the vector inversion process of antisaccades and differ markedly
      from those involved in forward adaptation.

PMID- 19091923
TI  - Force-EMG changes during sustained contractions of a human upper airway muscle.
AB  - Human upper airway and facial muscles support breathing, swallowing, speech,
      mastication, and facial expression, but their endurance performance in sustained
      contractions is poorly understood. The muscular fatigue typically associated with
      task failure during sustained contractions has both central and intramuscular
      causes, with the contribution of each believed to be task dependent. Previously
      we failed to show central fatigue in the nasal dilator muscles of subjects that
      performed intermittent maximal voluntary contractions (MVCs). Here we test the
      hypothesis that central mechanisms contribute to the fatigue of submaximal,
      sustained contractions in nasal dilator muscles. Nasal dilator muscle force and
      EMG activities were recorded in 11 subjects that performed submaximal
      contractions (20, 35, and 65% MVC) until force dropped to <or=90% of the target
      force for >or=3 s, which we defined as task failure. MVC and twitch forces (the
      latter obtained by applying supramaximal shocks to the facial nerve) were
      recorded before the trial and at several time points over the first 10 min of
      recovery. The time to task failure was inversely related to contraction
      intensity. MVC force was depressed by roughly 30% at task failure in all three
      trials, but recovered within 2 min. Twitch force fell by 30-44% depending on
      contraction intensity and remained depressed after 10 min of recovery, consistent
      with low-frequency fatigue. Average EMG activity increased with time, but never
      exceeded 75% of the maximal, pretrial level despite task failure. EMG mean power
      frequency declined by 20-25% in all trials, suggesting reduced action potential
      conduction velocity at task failure. In contrast, the maximal evoked potential
      did not change significantly in any of the tasks, indicating that the EMG deficit
      at task failure was due largely to mechanisms proximal to the neuromuscular
      junction. Additional experiments using the interpolated twitch technique suggest
      that subjects can produce about 92% of the maximal evocable force with this
      muscle, which is not a large enough deficit to explain the entire shortfall in
      the EMG at task failure. These data show that the nervous system fails to fully
      activate the nasal dilator muscles during sustained, submaximal contractions;
      putative mechanisms are discussed.

PMID- 19091925
TI  - Postsynaptic receptive field size and spike threshold determine encoding of high
      frequency information via sensitivity to synchronous presynaptic activity.
AB  - Parallel sensory streams carrying distinct information about various stimulus
      properties have been observed in several sensory systems, including the visual
      system. What remains unclear is why some of these streams differ in the size of
      their receptive fields (RFs). In the electrosensory system, neurons with large
      RFs have short-latency responses and are tuned to high-frequency inputs.
      Conversely, neurons with small RFs are low-frequency tuned and exhibit longer
      latency responses. What principle underlies this organization? We show
      experimentally that synchronous electroreceptor afferent (P-unit) spike trains
      selectively encode high-frequency stimulus information from broadband signals.
      This finding relies on a comparison of stimulus-spike output coherence using
      output trains obtained by either summing pairs of recorded afferent spike trains
      or selecting synchronous spike trains based on coincidence within a small time
      window. We propose a physiologically realistic decoding mechanism, based on
      postsynaptic RF size and postsynaptic output rate normalization that tunes target
      pyramidal cells in different electrosensory maps to low- or high-frequency signal
      components. By driving realistic neuron models with experimentally obtained P
      unit spike trains, we show that a small RF is matched with a postsynaptic
      integration regime leading to responses over a broad range of frequencies, and a
      large RF with a fluctuation-driven regime that requires synchronous presynaptic
      input and therefore selectively encodes higher frequencies, confirming recent
      experimental data. Thus our work reveals that the frequency content of a
      broadband stimulus extracted by pyramidal cells, from P-unit afferents, depends
      on the amount of feedforward convergence they receive.

PMID- 19091924
TI  - Temporal structure of receptor neuron input to the olfactory bulb imaged in
      behaving rats.
AB  - The dynamics of sensory input to the nervous system play a critical role in
      shaping higher-level processing. In the olfactory system, the dynamics of input
      from olfactory receptor neurons (ORNs) are poorly characterized and depend on
      multiple factors, including respiration-driven airflow through the nasal cavity,
      odorant sorption kinetics, receptor-ligand interactions between odorant and
      receptor, and the electrophysiological properties of ORNs. Here, we provide a
      detailed characterization of the temporal organization of ORN input to the
      mammalian olfactory bulb (OB) during natural respiration, using calcium imaging
      to monitor ORN input to the OB in awake, head-fixed rats expressing odor-guided
      behaviors. We report several key findings. First, across a population of
      homotypic ORNs, each inhalation of odorant evokes a burst of action potentials
      having a rise time of about 80 ms and a duration of about 100 ms. This rise time
      indicates a relatively slow, progressive increase in ORN activation as odorant
      flows through the nasal cavity. Second, the dynamics of ORN input differ among
      glomeruli and for different odorants and concentrations, but remain reliable
      across successive inhalations. Third, inhalation alone (in the absence of
      odorant) evokes ORN input to a significant fraction of OB glomeruli. Finally,
      high-frequency sniffing of odorant strongly reduces the temporal coupling between
      ORN inputs and the respiratory cycle. These results suggest that the dynamics of
      sensory input to the olfactory system may play a role in coding odor information
      and that, in the awake animal, strategies for processing odor information may
      change as a function of sampling behavior.

PMID- 19091926
TI  - Time course of cross-orientation suppression in the early visual cortex.
AB  - Responses of a visual neuron to optimally oriented stimuli can be suppressed by a
      superposition of another grating with a different orientation. This effect is
      known as cross-orientation suppression. However, it is still not clear whether
      the effect is intracortical in origin or a reflection of subcortical processes.
      To address this issue, we measured spatiotemporal responses to a plaid pattern, a
      superposition of two gratings, as well as to individual component gratings
      (optimal and mask) using a subspace reverse-correlation method. Suppression for
      the plaid was evaluated by comparing the response to that for the optimal
      grating. For component stimuli, excitatory and negative responses were defined as
      responses more positive and negative, respectively, than that to a blank
      stimulus. The suppressive effect for plaids was observed in the vast majority of
      neurons. However, only approximately 30% of neurons showed the negative response
      to mask-only gratings. The magnitudes of negative responses to mask-only stimuli
      were correlated with the degree of suppression for plaid stimuli. Comparing the
      latencies, we found that the suppression for the plaids starts at about the same
      time or slightly later than the response onset for the optimal grating and
      reaches its maximum at about the same time as the peak latency for the mask-only
      grating. Based on these results, we propose that in addition to the suppressive
      effect originating at the subcortical stage, delayed suppressive signals derived
      from the intracortical networks act on the neuron to generate cross-orientation
      suppression.

PMID- 19091928
TI  - Differential involvement of the anterior cingulate and primary sensorimotor
      cortices in sensory and affective functions of pain.
AB  - The present study examined the role of neurons in different pain-related
      functions of the anterior cingulate cortex (ACC) and primary sensorimotor cortex
      (SmI) by assessing their abilities to code different levels of noxious heat and
      activity changes evoked by classical fear conditioning involving electric shocks.
      Multiple single-unit activity was recorded with microwires implanted in the SmI
      and ACC of each rat. In the first set of experiments, the middle segment of the
      tail in each rat was irradiated with laser-heat pulses of various intensities.
      Neuronal responses in both the SmI and ACC increased with the intensity of the
      laser heat, although there was a significantly higher percentage of intensity
      related units in the SmI. Furthermore, the stimulus-response curve of SmI
      ensemble activity had a steeper slope than that of the ACC. In the second set of
      experiments, rats were trained and tested on a conditioned fear-potentiated
      startle task in which a light was paired with an electric shock and, later, the
      startle response was elicited by a burst of noise in the presence or absence of
      light. A higher percentage of ACC units changed their neuronal responses to the
      conditioned stimulus after the light-shock pairing and the average activity
      change was also significantly stronger. Our results suggest that SmI neurons are
      better at coding laser-heat intensity than ACC neurons, whereas more ACC neurons
      are involved in conditioned fear associated with an electric shock than SmI
      neurons. These data provide evidence for differential contributions of the SmI
      and ACC to sensory and affective dimensions of pain.

PMID- 19091927
TI  - Abolishment of serotonergic neurotransmission to cardiac vagal neurons during and
      after hypoxia and hypercapnia with prenatal nicotine exposure.
AB  - Cardioinhibitory cardiac vagal neurons (CVNs) do not receive inspiratory-related
      excitatory inputs under normal conditions. However, excitatory purinergic and
      serotonergic pathways are recruited during inspiratory activity after episodes of
      hypoxia and hypercapnia (H/H). Prenatal nicotine (PNN) exposure is known to
      dramatically change cardiorespiratory responses and decrease the ability to
      resuscitate from H/H. This study tested whether PNN exposure alters excitatory
      neurotransmission to CVNs in the nucleus ambiguus during and after H/H.
      Spontaneous and inspiratory evoked excitatory postsynaptic currents were recorded
      in CVNs from rats that were exposed to nicotine (6 mg x kg(-1) x d(-1))
      throughout the prenatal period. In contrast to unexposed animals, in PNN animals
      H/H recruited excitatory neurotransmission to CVNs during inspiratory-related
      activity that was blocked by the alpha3beta4 nicotinic acetylcholine receptor
      (nAChR) blocker alpha-conotoxin AuIB (alpha-CTX AuIB, 100 microM) and 6-cyano-7
      nitroquinoxaline-2,3-dione (CNQX, 50 microM) and d(-)-2-amino-5
      phosphonopentanoic acid (AP5, 50 microM), selective AMPA/kainate and N-methyl-d
      aspartate receptor blockers, respectively. Following H/H, there was a significant
      increase in inspiratory-related excitatory postsynaptic currents that were
      unaltered by alpha-CTX AuIB or ondansetron, a 5-HT3 receptor blocker, but were
      subsequently inhibited by pyridoxalphosphate-6-azophenyl-2', 4'-disulphonic acid
      (100 microM), a purinergic receptor blocker and CNQX and AP5. The results from
      this study demonstrate that with PNN exposure, an excitatory neurotransmission to
      CVNs is recruited during H/H that is glutamatergic and dependent on activation of
      alpha3beta4-containing nAChRs. Furthermore, exposure to PNN abolishes a
      serotonergic long-lasting inspiratory-related excitation of CVNs that is replaced
      by recruitment of a glutamatergic pathway to CVNs post H/H.

PMID- 19091929
TI  - Role of inhibitory neurotransmission in the control of canine hypoglossal
      motoneuron activity in vivo.
AB  - Hypoglossal motoneurons (HMNs) innervate all tongue muscles and are vital for
      maintenance of upper airway patency during inspiration. The relative
      contributions of the various synaptic inputs to the spontaneous discharge of HMNs
      in vivo are incompletely understood, especially at the cellular level. The
      purpose of this study was to determine the role of endogenously activated GABA(A)
      and glycine receptors in the control of the inspiratory HMN (IHMN) activity in a
      decerebrate dog model. Multibarrel micropipettes were used to record
      extracellular unit activity of individual IHMNs during local antagonism of
      GABA(A) receptors with bicuculline and picrotoxin or glycine receptors with
      strychnine. Only bicuculline had a significant effect on peak and average
      discharge frequency and on the slope of the augmenting neuronal discharge
      pattern. These parameters were increased by 30 +/- 7% (P < 0.001), 30 +/- 8% (P <
      0.001), and 25 +/- 7% (P < 0.001), respectively. The effects of picrotoxin and
      strychnine on the spontaneous neuronal discharge and its pattern were negligible.
      Our data suggest that bicuculline-sensitive GABAergic, but not picrotoxin
      sensitive GABAergic or glycinergic, inhibitory mechanisms actively attenuate the
      activity of IHMNs in vagotomized decerebrate dogs during hyperoxic hypercapnia.
      The pattern of GABAergic attenuation of IHMN discharge is characteristic of gain
      modulation similar to that in respiratory bulbospinal premotor neurons, but the
      degree of attenuation ( approximately 25%) is less than that seen in bulbospinal
      premotor neurons ( approximately 60%). The current studies only assess effects on
      active neuron discharge and do not resolve whether the lack of effect of
      picrotoxin and strychnine on IHMNs also extends to the inactive expiratory phase.

PMID- 19091931
TI  - Taking tablets for chronic illness: where next?

PMID- 19091930
TI  - Adjustments of motor pattern for load compensation via modulated activations of
      muscle synergies during natural behaviors.
AB  - It has been suggested that the motor system may circumvent the difficulty of
      controlling many degrees of freedom in the musculoskeletal apparatus by
      generating motor outputs through a combination of discrete muscle synergies. How
      a discretely organized motor system compensates for diverse perturbations has
      remained elusive. Here, we investigate whether motor responses observed after an
      inertial-load perturbation can be generated by altering the recruitment of
      synergies normally used for constructing unperturbed movements. Electromyographic
      (EMG, 13 muscles) data were collected from the bullfrog hindlimb during natural
      behaviors before, during, and after the same limb was loaded by a weight attached
      to the calf. Kinematic analysis reveals the absence of aftereffect on load
      removal, suggesting that load-related EMG changes were results of immediate motor
      pattern adjustments. We then extracted synergies from EMGs using the nonnegative
      matrix factorization algorithm and developed a procedure for assessing the extent
      of synergy sharing across different loading conditions. Most synergies extracted
      were found to be activated in all loaded and unloaded conditions. However, for
      certain synergies, the amplitude, duration, and/or onset time of their activation
      bursts were up- or down-modulated during loading. Behavioral parameterizations
      reveal that load-related modulation of synergy activations depended on the
      behavioral variety (e.g., kick direction and amplitude) and the movement phase
      performed. Our results suggest that muscle synergies are robust across different
      dynamic conditions and immediate motor adjustments can be accomplished by
      modulating synergy activations. An appendix describes the novel procedure we
      developed, useful for discovering shared and specific features from multiple data
      sets.

PMID- 19091932
TI  - Social interactions in an online self-management program for rheumatoid
      arthritis.
AB  - OBJECTIVE: To evaluate social interactions among individuals with rheumatoid
      arthritis (RA), participating in an empirically based, cognitive-behavioural,
      self-management (SM), and peer-support program, delivered in an online format.
      METHODS: Thirty individuals with RA were recruited online. Subjects were a subset
      of participants in the treatment arm of a waiting-list controlled study testing
      the effectiveness of a 10-week, online, SM education and peer support program.
      Primary outcomes were process variables describing social activity in the online
      environment during active treatment. Qualitative review of discussion board posts
      was undertaken to gain insight into participants' perceptions of social
      interactions. RESULTS: Participants spent a large proportion of logged-in time
      accessing educational materials and community-level activity was vibrant, with
      members utilizing the discussion board and e-mail. The Chat feature was less well
      used. Discussion board posts regarding RAHelp were very positive, especially in
      regard to perceived supportiveness and bonding among participants, and a sense of
      feeling uniquely understood by others who have RA. Concern arose in response to
      periods in which the discussion board was 'too quiet'. DISCUSSION: Our work
      complements the emerging literature supporting acceptance and utility of Internet
      based programming as a venue for SM education and social interaction among
      individuals with chronic illness.

PMID- 19091933
TI  - The Expert Patients Programme online, a 1-year study of an Internet-based self
      management programme for people with long-term conditions.
AB  - OBJECTIVES: Evaluate the effectiveness of an online self-management programme
      (EPP Online) for England residents with long-term conditions. METHODS: A
      prospective longitudinal study. Data were collected online at baseline, 6 and 12
      months. The intervention was an asynchronous 6-week chronic-disease self
      management programme offered online. We measured seven health status measures
      (health distress, self-rated health, illness intrusiveness, disability, fatigue,
      pain and shortness of breath), four behaviours (aerobic exercise, stretching
      exercise, stress management and communications with physician), and five
      utilization measures (GP visits, pharmacy visits, PT/OT visits, emergency visits
      and hospitalizations). We also measured self-efficacy and satisfaction with the
      health care system. RESULTS: A total of 568 completed baseline data: 546 (81%)
      completed 6 months and 443 (78%) completed 1 year. Significant improvements (p <
      0.01) were found at 6 months for all variables except self-rated health,
      disability, stretching, hospitalizations and nights in hospital. At 12 months
      only decrease in disability, nights in hospital and hospitalizations were not
      significant with reduction in visits to emergency departments being marginally
      significant (p = 0.012). Both self-efficacy and satisfaction with the health care
      system improved significantly. DISCUSSION: The peer-led online programme
      conditions appears to decrease symptoms, improve health behaviours, self-efficacy
      and satisfaction with the health care system and reducing health care utilization
      up to 1 year.

PMID- 19091934
TI  - The Arabic version of Diabetes-39: psychometric properties and validation.
AB  - OBJECTIVE: To translate Diabetes-39 (D-39) into Arabic language and assess its
      psychometric properties among patients with type 2 diabetes in Jordan. METHODS: A
      sample of 368 subjects (162 men and 206 women) was randomly selected from
      patients with type 2 diabetes attending outpatient clinics in King Abdullah
      University Hospital (KAUH). D-39 was translated using backward forward
      translation method. Individual D-39 items were recoded, summed and transformed to
      a 0 to 100-scale. Acceptability, item level validity, scale level validity and
      reliability were evaluated. RESULTS: The mean (SD) of D-39 subscales ranged from
      26.9 (22.4) for 'Social burden' to 50.5 (21.1) for 'Energy and Mobility'. Inter
      item correlations within each scale were moderate to strong. All item-scale
      correlations exceeded the minimum correlation of 0.40 for adequate item internal
      consistency. Item discriminat validity was demonstrated since items correlated
      higher with their own scale than with other scales. For all scales, Cronbach's
      alpha coefficient exceeded the minimum criterion of 0.7. CONCLUSIONS: Arabic
      version of D-39 is a reliable and valid instrument to measure quality of life
      among patients with diabetes in Jordan.

PMID- 19091935
TI  - The patient's experience of holistic care: insights from acupuncture research.
AB  - OBJECTIVES: To characterize the diverse nature of peoples' experiences of
      acupuncture treatment for chronic health problems. Specifically, the paper
      addresses how this analysis deepens our understanding of holism and its relation
      to the therapeutic theory base. METHODS: A secondary analysis of five
      longitudinal interview studies using a constant comparative method. Patients
      experienced different types of acupuncture--traditional (based on Chinese
      medicine) and Western-style (based on biomedicine) in a variety of settings in
      the U.K. and Australia. RESULTS: The markedly different experiences of
      acupuncture treatment were best characterized in relation to the concept of
      holism. Being treated ;as a whole person' was associated with traditional
      acupuncture in both private and NHS practice, but not within a research trial
      setting. In the trial, both patients and practitioners ;played their part' in a
      scientific experiment. Holism was especially important to people with several
      health problems. DISCUSSION: The findings suggests that the experience of
      holistic care, in the sense of ;being treated as a whole person' is dependent on
      four factors: (a) the therapeutic theory that underpins the treatment; (b)
      structural factors such as time and setting; (c) the intention of the
      practitioner; and (d) the intention and needs of the patient.

PMID- 19091936
TI  - Living with cystic fibrosis-related diabetes or type 1 diabetes mellitus: a
      comparative study exploring health-related quality of life and patients' reported
      experiences of hypoglycaemia.
AB  - OBJECTIVES: To compare patients with type 1 diabetes mellitus (T1DM) or cystic
      fibrosis-related diabetes (CFRD) on frequency and severity of symptoms suggestive
      of hypoglycaemia and diabetes-specific health-related quality of life (HRQoL).
      METHODS: This was a cross-sectional comparison study. Participants with T1DM or
      CFRD completed a questionnaire that assessed symptoms suggestive of hypoglycaemia
      and diabetes-specific HRQoL, and recorded episodes of low blood sugars in a
      prospective diary. Comparisons of responses were conducted, and Pearson product
      correlations were determined between HRQoL scores and other continuous variables.
      HRQoL scores were compared between the groups after adjusting for confounding
      factors. RESULTS: Diabetes in cystic fibrosis (CF) patients had a less negative
      impact on HRQoL than in T1DM patients. Both groups experienced hypoglycaemia, but
      loss of consciousness or needing help was more common in T1DM patients. Symptoms
      suggestive of hypoglycaemia were less of a problem for CFRD patients in terms of
      severity, with T1DM patients having more neuroglycopenic symptoms. DISCUSSION:
      Although the same percentage of patients in both groups reported experiencing
      hypoglycaemia, severity (e.g. symptoms and loss of consciousness) was higher for
      those with T1DM. Symptoms of hypoglycaemia appear to have a significant impact on
      HRQoL, and could account for the worse HRQoL in T1DM patients.

PMID- 19091937
TI  - Are fuel poverty reduction schemes associated with decreased excess winter
      mortality in elders? A case study from London, U.K.
AB  - The London Borough of Newham, London piloted the Warm Zone, a government-led fuel
      poverty reduction scheme. Fuel poverty is often cited as a factor in excess
      winter mortality (EWM) in the U.K. This study reported in this paper assessed
      whether EWM decreased for people aged > or =65 years in Newham as compared to all
      London, employing data from before and throughout the duration of the Warm Zone
      project. The paper also discusses the difficulties surrounding the measurement
      and interpretation of health impact relating to fuel poverty. We calculated and
      compared the yearly EWM indices for people aged > or =65 years for all of London,
      and for Newham over 12 years (1993-2005). The yearly EWM ratio for Newham in
      relation to all London was then calculated and compared. No definitive evidence
      to support the effect of the War Zone on EMW were noted. Relationships between
      EWM and fewer poverty reduction schemes are difficult to interpret, as many
      factors are entangled. These include cold strain and biological, genetic, gender,
      physiological, thermoregulation, environmental, meteorological, socio-economic,
      healthcare provision/expenditure, lifestyle and co-morbidity aspects, besides the
      challenges of sample sizes and whether other fuel poverty reduction schemes were
      simultaneously in operation. Those in privately owned housing might be ;masked'
      (underestimated) in their vulnerability to fuel poverty. Redefining the specific
      criteria for eligibility for fuel poverty grants and tackling heat inefficiency
      in privately owned homes not eligible for home heating improvement despite
      fulfilling other criteria for vulnerability requires attention. The implications
      are discussed.

PMID- 19091938
TI  - 'Recovery' and current mental health policy.
AB  - This article examines a central plank of current mental health policy-
      'recovery'. The latter is being used increasingly as a harbinger of progress,
      when discussing improvements in service quality and social inclusion. Mainly
      using Britain as a case study, different usages of the term are considered on the
      part of three main interest groups: traditional biomedical psychiatrists; social
      psychiatrists emphasizing social skills training; and dissenting service users.
      These different usages suggest that 'recovery' is a polyvalent concept, which
      creates an uneasy consensus point to define the management philosophies of local
      services enacting mental health policy. It has also emerged during a time when
      government health policy is seeking to support people with chronic conditions in
      community settings on the one hand and minimize the risks they might pose on the
      other. This tension is particularly relevant for those with mental health
      problems.

PMID- 19091939
TI  - 'Recovery' as a response to oppressive social structures.

PMID- 19091940
TI  - A confusion of tongues, a reform on hold.

PMID- 19091941
TI  - 'Recovery' and current mental health policy.

PMID- 19091942
TI  - A personal perspective on recovery.

PMID- 19091943
TI  - Highly parallel identification of essential genes in cancer cells.
AB  - More complete knowledge of the molecular mechanisms underlying cancer will
      improve prevention, diagnosis and treatment. Efforts such as The Cancer Genome
      Atlas are systematically characterizing the structural basis of cancer, by
      identifying the genomic mutations associated with each cancer type. A powerful
      complementary approach is to systematically characterize the functional basis of
      cancer, by identifying the genes essential for growth and related phenotypes in
      different cancer cells. Such information would be particularly valuable for
      identifying potential drug targets. Here, we report the development of an
      efficient, robust approach to perform genome-scale pooled shRNA screens for both
      positive and negative selection and its application to systematically identify
      cell essential genes in 12 cancer cell lines. By integrating these functional
      data with comprehensive genetic analyses of primary human tumors, we identified
      known and putative oncogenes such as EGFR, KRAS, MYC, BCR-ABL, MYB, CRKL, and
      CDK4 that are essential for cancer cell proliferation and also altered in human
      cancers. We further used this approach to identify genes involved in the response
      of cancer cells to tumoricidal agents and found 4 genes required for the response
      of CML cells to imatinib treatment: PTPN1, NF1, SMARCB1, and SMARCE1, and 5
      regulators of the response to FAS activation, FAS, FADD, CASP8, ARID1A and CBX1.
      Broad application of this highly parallel genetic screening strategy will not
      only facilitate the rapid identification of genes that drive the malignant state
      and its response to therapeutics but will also enable the discovery of genes that
      participate in any biological process.

PMID- 19091944
TI  - Analysis of nondegradative protein ubiquitylation with a monoclonal antibody
      specific for lysine-63-linked polyubiquitin.
AB  - Modification of proteins by the addition of lysine (K)-63-linked polyubiquitin
      (polyUb) chains is suggested to play important roles in a variety of cellular
      events, including DNA repair, signal transduction, and receptor endocytosis.
      However, identifying such modifications in living cells is complex and
      cumbersome. We have generated a monoclonal antibody (mAb) that specifically
      recognizes K63-linked polyUb, but not any other isopeptide-linked (K6, K11, K27,
      K29, K33, or K48) polyUb or monoubiquitin. We demonstrate the sensitivity and
      specificity of this K63Ub-specific mAb to detect K63Ub-modified proteins in cell
      lysates by Western blotting and in cells by immunofluorescence, and K63Ub
      modified TRAF6 and MEKK1 in vitro and ex vivo. This unique mAb will facilitate
      the analysis of K63-linked polyubiquitylation ex vivo and presents a strategy for
      the generation of similar reagents against other forms of polyUb.

PMID- 19091945
TI  - Four-dimensional realistic modeling of pancreatic organogenesis.
AB  - Organogenesis, the process by which organs develop from individual precursor stem
      cells, requires that the precursor cells proliferate, differentiate, and
      aggregate to form a functioning structure. This process progresses through
      changes in 4 dimensions: time and 3 dimensions of space-4D. Experimental analysis
      of organogenesis, by its nature, cuts the 4D developmental process into static,
      2D histological images or into molecular or cellular markers and interactions
      with little or no spatial dimensionality and minimal dynamics. Understanding
      organogenesis requires integration of the piecemeal experimental data into a
      running, realistic and interactive 4D simulation that allows experimentation and
      hypothesis testing in silico. Here, we describe a fully executable, interactive,
      visual model for 4D simulation of organogenic development using the mouse
      pancreas as a representative case. Execution of the model provided a dynamic
      description of pancreas development, culminating in a structure that remarkably
      recapitulated morphologic features seen in the embryonic pancreas. In silico
      mutations in key signaling molecules resulted in altered patterning of the
      developing pancreas that were in general agreement with in vivo data. The
      modeling approach described here thus typifies a useful platform for studying
      organogenesis as a phenomenon in 4 dimensions.

PMID- 19091946
TI  - Adrenal peripheral clock controls the autonomous circadian rhythm of
      glucocorticoid by causing rhythmic steroid production.
AB  - Glucocorticoid (GC) is an adrenal steroid with diverse physiological effects. It
      undergoes a robust daily oscillation, which has been thought to be driven by the
      master circadian clock in the suprachiasmatic nucleus of the hypothalamus via the
      hypothalamus-pituitary-adrenal axis. However, we show that the adrenal gland has
      its own clock and that the peripheral clockwork is tightly linked to
      steroidogenesis by the steroidogenic acute regulatory protein. Examination of
      mice with adrenal-specific knockdown of the canonical clock protein BMAL1 reveals
      that the adrenal clock machinery is required for circadian GC production.
      Furthermore, behavioral rhythmicity is drastically affected in these animals,
      together with altered expression of Period1, but not Period2, in several
      peripheral organs. We conclude that the adrenal peripheral clock plays an
      essential role in harmonizing the mammalian circadian timing system by generating
      a robust circadian GC rhythm.

PMID- 19091947
TI  - Modeling the temporal evolution of the spindle assembly checkpoint and role of
      Aurora B kinase.
AB  - Faithful separation of chromosomes prior to cell division at mitosis is a highly
      regulated process. One family of serine/threonine kinases that plays a central
      role in regulation is the Aurora family. Aurora B plays a role in the spindle
      assembly checkpoint, in part, by destabilizing the localization of BubR1 and Mad2
      at centrosomes and responds to changes in tension caused by aberrant microtubule
      kinetochore attachments. Aurora B is overexpressed in a subset of cancers and is
      required for mitosis, making it an attractive anticancer target. Here, we use
      mathematical modeling to extend a current model of the spindle assembly
      checkpoint to incorporate all signaling kinetochores within a cell rather than
      just one and the role of Aurora B within the resulting model. We find that the
      current model of the spindle assembly checkpoint is robust to variation in its
      key diffusion-limited parameters. Furthermore, when Aurora B inhibition is
      considered within the model, for a certain range of inhibitor concentrations, a
      prolonged prometaphase/metaphase is observed. This level of inhibitor
      concentrations has not yet been studied experimentally, to the authors' best
      knowledge. Therefore, experimental verification of the results discussed here
      could provide a deeper understanding of how kinetochores and Aurora B cooperate
      in the spindle assembly checkpoint.

PMID- 19091949
TI  - A proviral puzzle with a prosimian twist.

PMID- 19091948
TI  - Severe growth retardation and early lethality in mice lacking the nuclear
      localization sequence and C-terminus of PTH-related protein.
AB  - Parathyroid hormone (PTH) plays a central role in the regulation of serum calcium
      and phosphorus homeostasis, while parathyroid hormone-related protein (PTHrP) has
      important developmental roles. Both peptides signal through the same G protein
      coupled receptor, the PTH/PTHrP or PTH type 1 receptor (PTH1R). PTHrP, normally a
      secreted protein, also contains a nuclear localization signal (NLS) that in vitro
      imparts functionality to the protein at the level of the nucleus. We investigated
      this functionality in vivo by introducing a premature termination codon in Pthrp
      in ES cells and generating mice that express PTHrP (1-84), a truncated form of
      the protein that is missing the NLS and the C-terminal region of the protein but
      can still signal through its cell surface receptor. Mice homozygous for the knock
      in mutation (Pthrp KI) displayed retarded growth, early senescence, and
      malnutrition leading postnatally to their rapid demise. Decreased cellular
      proliferative capacity and increased apoptosis in multiple tissues including bone
      and bone marrow cells were associated with altered expression and subcellular
      distribution of the senescence-associated tumor suppressor proteins p16(INK4a)
      and p21 and the oncogenes Cyclin D, pRb, and Bmi-1. These findings provide in
      vivo experimental proof that substantiates the biologic relevance of the NLS and
      C-terminal portion of PTHrP, a polypeptide ligand that signals mainly via a cell
      surface G protein-coupled receptor.

PMID- 19091950
TI  - Volume-selective magnetic resonance imaging using an adjustable, single-sided,
      portable sensor.
AB  - Portable, single-sided NMR sensors can operate under conditions inaccessible to
      conventional NMR while featuring lower cost, portability, and the ability to
      analyze arbitrary-sized objects. Such sensors can nondestructively probe the
      interior of samples by collecting images and measuring relaxation and diffusion
      constants, and, given careful shimming schemes, even perform chemical analysis.
      The inherently strong magnetic-field gradients of single-sided sensors developed
      so far has prevented imaging of materials with high water content, such as
      biological tissues, over large volumes whereas designs with more homogeneous
      fields suffer from low field strength and typically cannot probe volumes larger
      than approximately 10 cm(3). We present a design with a continuously adjustable
      sensitive volume, enabling the effective volume to be enlarged several fold. This
      capability allows for imaging in reasonable times of much bigger objects and
      opens the door to the possibility of clinical imaging with portable sensors. We
      demonstrate MRI in axial and sagittal planes, at different depths of the
      sensitive volume and T(1)-weighted contrast in a tissue sample.

PMID- 19091951
TI  - The spt-function of Andrews.
AB  - Recently, Andrews introduced the function s(n) = spt(n) which counts the number
      of smallest parts among the integer partitions of n. We show that its generating
      function satisfies an identity analogous to Ramanujan's mock theta identities. As
      a consequence, we are able to completely determine the parity of s(n). Using
      another type of identity, one based on Hecke operators, we obtain a complete
      multiplicative theory for s(n) modulo 3. These congruences confirm unpublished
      conjectures of Garvan and Sellers. Our methods generalize to all integral moduli.

PMID- 19091952
TI  - The eocyte hypothesis and the origin of eukaryotic cells.

PMID- 19091953
TI  - Visualizing stimulus convergence in amygdala neurons during associative learning.
AB  - A central feature of models of associative memory formation is the reliance on
      information convergence from pathways responsive to the conditioned stimulus (CS)
      and unconditioned stimulus (US). In particular, cells receiving coincident input
      are held to be critical for subsequent plasticity. Yet identification of neurons
      in the mammalian brain that respond to such coincident inputs during a learning
      event remains elusive. Here we use Arc cellular compartmental analysis of
      temporal gene transcription by fluorescence in situ hybridization (catFISH) to
      locate populations of neurons in the mammalian brain that respond to both the CS
      and US during training in a one-trial learning task, conditioned taste aversion
      (CTA). Individual neurons in the basolateral nucleus of the amygdala (BLA)
      responded to both the CS taste and US drug during conditioning. Coincident
      activation was not evident, however, when stimulus exposure was altered so as to
      be ineffective in promoting learning (backward conditioning, latent inhibition).
      Together, these data provide clear visualization of neurons in the mammalian
      brain receiving convergent information about the CS and US during acquisition of
      a learned association.

PMID- 19091954
TI  - Essential function of Chk1 can be uncoupled from DNA damage checkpoint and
      replication control.
AB  - Chk1 is widely known as a DNA damage checkpoint signaling protein. Unlike many
      other checkpoint proteins, Chk1 also plays an essential but poorly defined role
      in the proliferation of unperturbed cells. Activation of Chk1 after DNA damage is
      known to require the phosphorylation of several C-terminal residues, including
      the highly conserved S317 and S345 sites. To evaluate the respective roles of
      these individual sites and assess their contribution to the functions of Chk1, we
      used a gene targeting approach to introduce point mutations into the endogenous
      human CHK1 locus. We report that the essential and nonessential functions of Chk1
      are regulated through distinct phosphorylation events and can be genetically
      uncoupled. The DNA damage response function of Chk1 was nonessential. Targeted
      mutation of S317 abrogated G(2)/M checkpoint activation, prevented subsequent
      phosphorylation of Chk1, impaired efficient progression of DNA replication forks,
      and increased fork stalling, but did not impact viability. Thus, the nonessential
      DNA damage response function of Chk1 could be unambiguously linked to its role in
      DNA replication control. In contrast, a CHK1 allele with mutated S345 did not
      support viability, indicating an essential role for this residue during the
      unperturbed cell cycle. A distinct, physiologic mode of S345 phosphorylation,
      initiated at the centrosome during unperturbed mitosis was independent of codon
      317 status and mechanistically distinct from the ordered and sequential
      phosphorylation of serine residues on Chk1 induced by DNA damage. Our findings
      suggest an essential regulatory role for Chk1 phosphorylation during mitotic
      progression.

PMID- 19091955
TI  - A dual-signal regulatory circuit activates transcription of a set of divergent
      operons in Salmonella typhimurium.
AB  - We present a molecular mechanism for signal transduction that activates
      transcription of the SlyA regulon in Salmonella typhimurium. We demonstrate that
      SlyA mediates transcriptional activation in response to guanosine tetraphosphate,
      ppGpp, according to the following observations: (i) in vivo transcription of SlyA
      dependent genes is repressed when ppGpp is absent; this transcription can be
      restored by overproducing SlyA; (ii) in vivo dimerization and binding of SlyA to
      the target promoter are facilitated in the presence of ppGpp; and (iii) in vitro
      SlyA binding to the target promoter is enhanced when ppGpp is supplemented. Thus,
      ppGpp must be the cytoplasmic component that stimulates SlyA regulatory function
      by interacting directly with this regulator in Salmonella. This signaling domain,
      integrated by the PhoP/PhoQ 2-component system that activates slyA transcription
      by sensing Mg(2+), forms feedforward loops that regulate chromosomal loci
      identified through a motif search over the S. typhimurium genome. Many such loci
      are divergent operons, each formed by 2 neighboring genes in which transcription
      of these 2 loci proceeds in opposite directions. Both genes, however, are
      controlled by PhoP and SlyA through a single shared PhoP box and SlyA box present
      in their intergenic regions. A substitution in either box sequence causes a
      simultaneous cessation of transcription of a divergent operon, pagD-pagC,
      equivalent to the phenotype in a phoP or slyA mutant. We also identified several
      chromosomal loci that possess pagC-type genes without the cognate pagD-type
      genes. Therefore, our results provide a molecular basis for the understanding of
      SlyA-dependent phenotypes associated with Salmonella virulence.

PMID- 19091956
TI  - How CYCLOPS keeps an eye on plant symbiosis.

PMID- 19091957
TI  - Cytosolic phospholipase A2-{alpha} is an early apoptotic activator in PEDF
      induced endothelial cell apoptosis.
AB  - Pigment epithelium-derived factor (PEDF) is an intrinsic antiangiogenic factor
      and a potential therapeutic agent. Previously, we discovered the mechanism of
      PEDF-induced apoptosis of human umbilical vein endothelial cells (HUVECs) as
      sequential induction/activation of p38 mitogen-activated protein kinase (MAPK),
      peroxisome proliferator-activated receptor gamma (PPAR-gamma), and p53. In the
      present study, we investigated the signaling role of cytosolic calcium-dependent
      phospholipase A(2)-alpha (cPLA(2)-alpha) to bridge p38 MAPK and PPAR-gamma
      activation. PEDF induced cPLA(2)-alpha activation in HUVECs and in endothelial
      cells in chemical burn-induced vessels on mouse cornea. The cPLA(2)-alpha
      activation is evident from the phosphorylation and nuclear translocation of
      cPLA(2)-alpha as well as arachidonic acid release and the cleavage of PED6, a
      synthetic PLA(2) substrate. Such activation can be abolished by p38 MAPK
      inhibitor. The PEDF-induced PPAR-gamma activation, p53 expression, caspase-3
      activity, and apoptosis can be abolished by both cPLA(2) inhibitor and small
      interfering RNA targeting cPLA(2)-alpha. Our observation not only establishes the
      signaling role of cPLA(2)-alpha but also for the first time demonstrates the
      sequential activation of p38 MAPK, cPLA(2)-alpha, PPAR-gamma, and p53 as the
      mechanism of PEDF-induced endothelial cell apoptosis.

PMID- 19091958
TI  - The amino-terminal peptide of Bax perturbs intracellular Ca2+ homeostasis to
      enhance apoptosis in prostate cancer cells.
AB  - During apoptosis, proteolytic cleavage of Bax at the amino terminus generates a
      truncated Bax of approximately 18 kDa (p18Bax) and an amino-terminal peptide of
      approximately 3 kDa (p3Bax). Whereas extensive studies have shown that p18Bax
      behaves like a BH3 protein with enhanced pro-apoptotic function over that of the
      full-length Bax (p21Bax), little is known about the function of p3Bax in
      apoptosis. We have previously shown that Bax and Ca2+ play a synergistic role in
      amplifying apoptosis signaling and that store-operated Ca2+ entry (SOCE)
      contributes to Bax-mediated apoptosis in prostate cancer cells. Here we test
      whether p3Bax can contribute to regulation of Ca2+ signaling during apoptosis
      through use of a membrane-penetrating peptide to facilitate delivery of
      recombinant p3Bax into NRP-154 cells, a prostate epithelial cell line with
      tumorigenic capacity. We find that human immunodefficiency virus transactivator
      of transcription protein (TAT)-p3Bax fusion peptide can enhance thapsigargin
      induced apoptosis in NRP-154 cells, elevate SOCE activity, and increase inositol
      1,4,5-trisphosphate-sensitive intracellular Ca2+ stores. Our data indicates that
      p3Bax can modulate the entry of extracellular Ca2+ and thus regulate the
      amplification of apoptosis in prostate cancer cells.

PMID- 19091959
TI  - Sphingosine-1-phosphate inhibits high glucose-mediated ERK1/2 action in
      endothelium through induction of MAP kinase phosphatase-3.
AB  - Endothelial activation is a key early event in vascular complications of Type 1
      diabetes. The nonobese diabetic (NOD) mouse is a well-characterized model of Type
      1 diabetes. We previously reported that Type 1 diabetic NOD mice have increased
      endothelial activation, with increased production of monocyte chemoattractant
      protein (MCP)-1 and IL-6, and a 30% increase of surface VCAM-1 expression leading
      to a fourfold increase in monocyte adhesion to the endothelium. Sphingosine-1
      phosphate (S1P) prevents monocyte:endothelial interactions in these diabetic NOD
      mice. Incubation of diabetic NOD endothelial cells (EC) with S1P (100 nmol/l)
      reduced ERK1/2 phosphorylation by 90%, with no significant changes in total
      ERK1/2 protein. In the current study, we investigated the mechanism of S1P action
      on ERK1/2 to reduce activation of diabetic endothelium. S1P caused a significant
      threefold increase in mitogen-activated kinase phosphatase-3 (MKP-3) expression
      in EC. MKP-3 selectively regulates ERK1/2 activity through dephosphorylation.
      Incubation of diabetic NOD EC with S1P and the S1P(1)-selective agonist SEW2871
      significantly increased expression of MKP-3 and reduced ERK1/2 phosphorylation,
      while incubation with the S1P(1)/S1P(3) antagonist VPC23019 decreased the
      expression of MKP-3, both results supporting a role for S1P(1) in MKP-3
      regulation. To mimic the S1P-mediated induction of MKP-3 diabetic NOD EC, we
      overexpressed MKP-3 in human aortic endothelial cells (HAEC) cultured in elevated
      glucose (25 mmol/l). Overexpression of MKP-3 in glucose-cultured HAEC decreased
      ERK1/2 phosphorylation and resulted in decreased monocyte:endothelial
      interactions in a static monocyte adhesion assay. Finally, we used small
      interfering RNA to MKP-3 and observed increased monocyte adhesion. Moreover, S1P
      was unable to inhibit monocyte adhesion in the absence of MKP-3. Thus, one
      mechanism for the anti-inflammatory action of S1P in diabetic EC is inhibition of
      ERK1/2 phosphorylation through induction of MKP-3 expression via the S1P-S1P(1)
      receptor axis.

PMID- 19091960
TI  - Two PKC consensus sites on human acid-sensing ion channel 1b differentially
      regulate its function.
AB  - Human acid-sensing ion channel 1b (hASIC1b) is a H(+)-gated amiloride-sensitive
      cation channel. We have previously shown that glioma cells exhibit an amiloride
      sensitive cation conductance. Amiloride and the ASIC1 blocker psalmotoxin-1
      decrease the migration and proliferation of glioma cells. PKC also abolishes the
      amiloride-sensitive conductance of glioma cells and inhibits hASIC1b open
      probability in planar lipid bilayers. In addition, hASIC1b's COOH terminus has
      been shown to interact with protein interacting with C kinase (PICK)1, which
      targets PKC to the plasma membrane. Therefore, we tested the hypothesis that PKC
      regulation of hASIC1b at specific PKC consensus sites inhibits hASIC1b function.
      We mutated three consensus PKC phosphorylation sites (T26, S40, and S499) in
      hASIC1b to alanine, to prevent phosphorylation, and to glutamic acid or aspartic
      acid, to mimic phosphorylation. Our data suggest that S40 and S499 are critical
      sites mediating the modulation of hASIC1b by PKC. We expressed mutant hASIC1b
      constructs in Xenopus oocytes and measured acid-activated currents by two
      electrode voltage clamp. T26A and T26E did not exhibit acid-activated currents.
      S40A was indistinguishable from wild type (WT), whereas S40E, S499A, and S499D
      currents were decreased. The PKC activators PMA and phorbol 12,13-dibutyrate
      inhibited WT hASIC1b and S499A, and PMA had no effect on S40A or on WT hASIC1b in
      oocytes pretreated with the PKC inhibitor chelerythrine. Chelerythrine inhibited
      WT hASIC1b and S40A but had no effect on S499A or S40A/S499A. PKC activators or
      the inhibitor did not affect the surface expression of WT hASIC1b. These data
      show that the two PKC consensus sites S40 and S499 differentially regulate
      hASIC1b and mediate the effects of PKC activation or PKC inhibition on hASIC1b.
      This will result in a deeper understanding of PKC regulation of this channel in
      glioma cells, information that may help in designing potentially beneficial
      therapies in their treatment.

PMID- 19091961
TI  - Role of posterior parietal gamma activity in planning prosaccades and
      antisaccades.

PMID- 19091962
TI  - Region-specific spike-frequency acceleration in layer 5 pyramidal neurons
      mediated by Kv1 subunits.
AB  - Separation of the cortical sheet into functionally distinct regions is a hallmark
      of neocortical organization. Cortical circuit function emerges from afferent and
      efferent connectivity, local connectivity within the cortical microcircuit, and
      the intrinsic membrane properties of neurons that comprise the circuit. While
      localization of functions to particular cortical areas can be partially accounted
      for by regional differences in both long range and local connectivity, it is
      unknown whether the intrinsic membrane properties of cortical cell types differ
      between cortical regions. Here we report the first example of a region-specific
      firing type in layer 5 pyramidal neurons, and show that the intrinsic membrane
      and integrative properties of a discrete subtype of layer 5 pyramidal neurons
      differ between primary motor and somatosensory cortices due to region- and cell
      type-specific Kv1 subunit expression.

PMID- 19091963
TI  - Overexpressed transient receptor potential vanilloid 3 ion channels in skin
      keratinocytes modulate pain sensitivity via prostaglandin E2.
AB  - The ability to sense changes in the environment is essential for survival because
      it permits responses such as withdrawal from noxious stimuli and regulation of
      body temperature. Keratinocytes, which occupy much of the skin epidermis, are
      situated at the interface between the external environment and the body's
      internal milieu, and have long been appreciated for their barrier function
      against external insults. The recent discovery of temperature-sensitive transient
      receptor potential vanilloid (TRPV) ion channels in keratinocytes has raised the
      possibility that these cells also actively participate in acute temperature and
      pain sensation. To address this notion, we generated and characterized transgenic
      mice that overexpress TRPV3 in epidermal keratinocytes under the control of the
      keratin 14 promoter. Compared with wild-type controls, keratinocytes
      overexpressing TRPV3 exhibited larger currents as well as augmented prostaglandin
      E(2) (PGE(2)) release in response to two TRPV3 agonists, 2-aminoethoxydiphenyl
      borate (2APB) and heat. Thermal selection behavior and heat-evoked withdrawal
      behavior of naive mice overexpressing TRPV3 were not consistently altered. Upon
      selective pharmacological inhibition of TRPV1 with JNJ-17203212 [corrected],
      however, the keratinocyte-specific TRPV3 transgenic mice showed increased escape
      responses to noxious heat relative to their wild-type littermates.
      Coadministration of the cyclooxygenase inhibitor, ibuprofen, with the TRPV1
      antagonist decreased inflammatory thermal hyperalgesia in transgenic but not wild
      type animals. Our results reveal a previously undescribed mechanism for
      keratinocyte participation in thermal pain transduction through keratinocyte
      TRPV3 ion channels and the intercellular messenger PGE(2).

PMID- 19091964
TI  - Restoring Acid-sensing ion channel-1a in the amygdala of knock-out mice rescues
      fear memory but not unconditioned fear responses.
AB  - Acid-sensing ion channel-1a (ASIC1a) contributes to multiple fear behaviors,
      however the site of ASIC1a action in behavior is not known. To explore a specific
      location of ASIC1a action, we expressed ASIC1a in the basolateral amygdala of
      ASIC1a-/- mice using viral vector-mediated gene transfer. This rescued context
      dependent fear memory, but not the freezing deficit during training or the
      unconditioned fear response to predator odor. These data pinpoint the basolateral
      amygdala as the site where ASIC1a contributes to fear memory. They also
      discriminate fear memory from fear expressed during training and from
      unconditioned fear. Furthermore, this work illustrates a strategy for identifying
      discrete brain regions where specific genes contribute to complex behaviors.

PMID- 19091965
TI  - Organization and postembryonic development of glial cells in the adult central
      brain of Drosophila.
AB  - Glial cells exist throughout the nervous system, and play essential roles in
      various aspects of neural development and function. Distinct types of glia may
      govern diverse glial functions. To determine the roles of glia requires
      systematic characterization of glia diversity and development. In the adult
      Drosophila central brain, we identify five different types of glia based on its
      location, morphology, marker expression, and development. Perineurial and
      subperineurial glia reside in two separate single-cell layers on the brain
      surface, cortex glia form a glial mesh in the brain cortex where neuronal cell
      bodies reside, while ensheathing and astrocyte-like glia enwrap and infiltrate
      into neuropils, respectively. Clonal analysis reveals that distinct glial types
      derive from different precursors, and that most adult perineurial, ensheathing,
      and astrocyte-like glia are produced after embryogenesis. Notably, perineurial
      glial cells are made locally on the brain surface without the involvement of gcm
      (glial cell missing). In contrast, the widespread ensheathing and astrocyte-like
      glia derive from specific brain regions in a gcm-dependent manner. This study
      documents glia diversity in the adult fly brain and demonstrates involvement of
      different developmental programs in the derivation of distinct types of glia. It
      lays an essential foundation for studying glia development and function in the
      Drosophila brain.

PMID- 19091966
TI  - Regional variation in interhemispheric coordination of intrinsic hemodynamic
      fluctuations.
AB  - Electrophysiological studies have long demonstrated a high degree of correlated
      activity between the left and right hemispheres, however little is known about
      regional variation in this interhemispheric coordination. Whereas cognitive
      models and neuroanatomical evidence suggest differences in coordination across
      primary sensory-motor cortices versus higher-order association areas, these have
      not been characterized. Here, we used resting-state functional magnetic resonance
      imaging data acquired from 62 healthy volunteers to examine interregional
      correlation in spontaneous low-frequency hemodynamic fluctuations. Using a
      probabilistic atlas, we correlated probability-weighted time series from 112
      regions comprising the entire cerebrum. We then examined regional variation in
      correlated activity between homotopic regions, contrasting primary sensory-motor
      cortices, unimodal association areas, and heteromodal association areas.
      Consistent with previous studies, robustly correlated spontaneous activity was
      noted between all homotopic regions, which was significantly higher than that
      between nonhomotopic (heterotopic and intrahemispheric) regions. We further
      demonstrated substantial regional variation in homotopic interhemispheric
      correlations that was highly consistent across subjects. Specifically, there was
      a gradient of interhemispheric correlation, with highest correlations across
      primary sensory-motor cortices (0.758, SD=0.152), significantly lower
      correlations across unimodal association areas (0.597, SD=0.230) and still lower
      correlations across heteromodal association areas (0.517, SD=0.226). These
      results demonstrate functional differences in interhemispheric coordination
      related to the brain's hierarchical subdivisions. Synchrony across primary
      cortices may reflect networks engaged in bilateral sensory integration and motor
      coordination, whereas lower coordination across heteromodal association areas is
      consistent with functional lateralization of these regions. This novel method of
      examining interhemispheric coordination may yield insights regarding diverse
      disease processes as well as healthy development.

PMID- 19091967
TI  - Leukemia inhibitory factor extends the lifespan of injured photoreceptors in
      vivo.
AB  - Survival and death of photoreceptors in degenerative diseases of the retina is
      controlled by a multitude of genes and endogenous factors. Some genes may be
      involved in the degenerative process itself whereas others may be part of an
      endogenous defense system. We show in two models of retinal degeneration that
      photoreceptor death strongly induces expression of leukemia inhibitory factor
      (LIF) in a subset of Muller glia cells in the inner nuclear layer of the retina.
      LIF expression is essential to induce an extensive intraretinal signaling system
      which includes Muller cells and photoreceptors and is characterized by an
      upregulation of Edn2, STAT3, FGF2 and GFAP. In the absence of LIF, Muller cells
      remain quiescent, the signaling system is not activated and retinal degeneration
      is strongly accelerated. Intravitreal application of recombinant LIF induces the
      full molecular pathway including the activation of Muller cells in wild-type and
      Lif(-/-) mice. Interruption of the signaling cascade by an Edn2 receptor
      antagonist increases whereas activation of the receptor decreases photoreceptor
      cell death. Thus, LIF is essential and sufficient to activate an extensive
      molecular defense response to photoreceptor injury. Our data establish LIF as a
      Muller cell derived neuronal survival factor which controls an intrinsic
      protective mechanism that includes Edn2 signaling to support photoreceptor cell
      survival and to preserve vision in the injured retina.

PMID- 19091968
TI  - Frontal cortex subregions play distinct roles in choices between actions and
      stimuli.
AB  - The orbitofrontal cortex (OFC) has been implicated in reinforcement-guided
      decision making, error monitoring, and the reversal of behavior in response to
      changing circumstances. The anterior cingulate cortex sulcus (ACC(S)), however,
      has also been implicated in similar aspects of behavior. Dissociating the unique
      functions of these areas would improve our understanding of the decision-making
      process. The effect of selective OFC lesions on how monkeys used the history of
      reinforcement to guide choices of either particular actions or particular stimuli
      was studied and compared with the effects of ACC(S) lesions. Both lesions
      disrupted decision making, but their effects were differentially modulated by the
      dependence on action- or stimulus-value contingencies. OFC lesions caused a
      deficit in stimulus but not action selection, whereas ACC(S) lesions had the
      opposite effect, disrupting action but not stimulus selection. Furthermore, OFC
      lesions that have previously been found to impair decision making when
      deterministic stimulus-reward contingencies are switched were found to cause a
      more general learning impairment in more naturalistic situations in which reward
      was stochastic. Both OFC and ACC(S) are essential for reinforcement-guided
      decision making rather than just error monitoring or behavioral reversal. The OFC
      and ACC(S) are both, however, more concerned with learning and making decisions,
      but their roles in selecting between stimulus and action values are distinct.

PMID- 19091969
TI  - Attention enhances the neural processing of relevant features and suppresses the
      processing of irrelevant features in humans: a functional magnetic resonance
      imaging study of the Stroop task.
AB  - We present a functional MRI experiment investigating the neural basis of feature
      based attention in humans using the Stroop task. Cortical areas specifically
      involved in color processing and word reading were first identified in individual
      participants using independent tests. These areas were then probed during the
      Stroop task (in which participants must selectively attend to the font color of a
      word while ignoring the word itself). We found that activation in functionally
      defined color areas increased during the task relative to a neutral color-naming
      task while activation in functionally defined word areas decreased. These results
      are consistent with a biased competition model of feature-based attention in
      which the processing of attended features is enhanced and the processing of
      ignored features is suppressed.

PMID- 19091970
TI  - Dendrites of mammalian neurons contain specialized P-body-like structures that
      respond to neuronal activation.
AB  - Intracellular mRNA transport and local translation play a key role in neuronal
      physiology. Translationally repressed mRNAs are transported as a part of
      ribonucleoprotein (RNP) particles to distant dendritic sites, but the properties
      of different RNP particles and mechanisms of their repression and transport
      remain largely unknown. Here, we describe a new class of RNP-particles, the
      dendritic P-body-like structures (dlPbodies), which are present in the soma and
      dendrites of mammalian neurons and have both similarities and differences to P
      bodies of non-neuronal cells. These structures stain positively for a number of P
      body and microRNP components, a microRNA-repressed mRNA and some translational
      repressors. They appear more heterogeneous than P-bodies of HeLa cells, and they
      rarely contain the exonuclease Xrn1 but are positive for rRNA. These particles
      show motorized movements along dendrites and relocalize to distant sites in
      response to synaptic activation. Furthermore, Dcp1a is stably associated with dlP
      bodies in unstimulated cells, but exchanges rapidly on neuronal activation,
      concomitantly with the loss of Ago2 from dlP-bodies. Thus, dlP-bodies may
      regulate local translation by storing repressed mRNPs in unstimulated cells, and
      releasing them on synaptic activation.

PMID- 19091971
TI  - Amyloid pathology is associated with progressive monoaminergic neurodegeneration
      in a transgenic mouse model of Alzheimer's disease.
AB  - beta-Amyloid (Abeta) pathology is an essential pathogenic component in
      Alzheimer's disease (AD). However, the significance of Abeta pathology, including
      Abeta deposits/oligomers and glial reactions, to neurodegeneration is unclear. In
      particular, despite the Abeta neurotoxicity indicated by in vitro studies, mouse
      models with significant Abeta deposition lack robust and progressive loss of
      forebrain neurons. Such results have fueled the view that Abeta pathology is
      insufficient for neurodegeneration in vivo. In this study, because monoaminergic
      (MAergic) neurons show degenerative changes at early stages of AD, we examined
      whether the APPswe/PS1DeltaE9 mouse model recapitulates progressive MAergic
      neurodegeneration occurring in AD cases. We show that the progression forebrain
      Abeta deposition in the APPswe/PS1DeltaE9 model is associated with progressive
      losses of the forebrain MAergic afferents. Significantly, axonal degeneration is
      associated with significant atrophy of cell bodies and eventually leads to robust
      loss (approximately 50%) of subcortical MAergic neurons. Degeneration of these
      neurons occurs without obvious local Abeta or tau pathology at the subcortical
      sites and precedes the onset of anxiety-associated behavior in the mice. Our
      results show that a transgenic mouse model of Abeta pathology develops
      progressive MAergic neurodegeneration occurring in AD cases.

PMID- 19091973
TI  - Spontaneous high-frequency (10-80 Hz) oscillations during up states in the
      cerebral cortex in vitro.
AB  - High-frequency oscillations in cortical networks have been linked to a variety of
      cognitive and perceptual processes. They have also been recorded in small
      cortical slices in vitro, indicating that neuronal synchronization at these
      frequencies is generated in the local cortical circuit. However, in vitro
      experiments have hitherto necessitated exogenous pharmacological or electrical
      stimulation to generate robust synchronized activity in the beta/gamma range.
      Here, we demonstrate that the isolated cortical microcircuitry generates beta and
      gamma oscillations spontaneously in the absence of externally applied
      neuromodulators or synaptic agonists. We show this in a spontaneously active
      slice preparation that engages in slow oscillatory activity similar to activity
      during slow-wave sleep. beta and gamma synchronization appeared during the up
      states of the slow oscillation. Simultaneous intracellular and extracellular
      recordings revealed synchronization between the timing of incoming synaptic
      events and population activity. This rhythm was mechanistically similar to
      pharmacologically induced gamma rhythms, as it also included sparse, irregular
      firing of neurons within the population oscillation, predominant involvement of
      inhibitory neurons, and a decrease of oscillation frequency after barbiturate
      application. Finally, we show in a computer model how a synaptic loop between
      excitatory and inhibitory neurons can explain the emergence of both the slow (<1
      Hz) and the beta-range oscillations in the neocortical network. We therefore
      conclude that oscillations in the beta/gamma range that share mechanisms with
      activity reported in vivo or in pharmacologically activated in vitro preparations
      can be generated during slow oscillatory activity in the local cortical circuit,
      even without exogenous pharmacological or electrical stimulation.

PMID- 19091972
TI  - Trafficking and fusion of neuropeptide Y-containing dense-core granules in
      astrocytes.
AB  - It is becoming clear that astrocytes are active participants in synaptic
      functioning and exhibit properties, such as the secretion of classical
      transmitters, previously thought to be exclusively neuronal. Whether these
      similarities extend to the release of neuropeptides, the other major class of
      transmitters, is less clear. Here we show that cortical astrocytes can synthesize
      both native and foreign neuropeptides and can secrete them in a stimulation
      dependent manner. Reverse transcription-PCR and mass spectrometry indicate that
      cortical astrocytes contain neuropeptide Y (NPY), a widespread neuronal
      transmitter. Immunocytochemical studies reveal NPY-immunoreactive (IR) puncta
      that colocalize with markers of the regulated secretory pathway. These NPY-IR
      puncta are distinct from the synaptic-like vesicles that contain classical
      transmitters, and the two types of organelles are differentially distributed.
      After activation of metabotropic glutamate receptors and the release of calcium
      from intracellular stores, the NPY-IR puncta fuse with the cell membrane, and the
      peptide-containing dense cores are displayed. To determine whether peptide
      secretion subsequently occurred, exocytosis was monitored from astrocytes
      expressing NPY-red fluorescent protein (RFP). In live cells, after activation of
      glutamate receptors, the intensity of the NPY-RFP-labeled puncta declined in a
      step-like manner indicating a regulated release of the granular contents. Because
      NPY is a widespread and potent regulator of synaptic transmission, these results
      suggest that astrocytes could play a role in the peptidergic modulation of
      synaptic signaling in the CNS.

PMID- 19091974
TI  - Stable membrane expression of postsynaptic CaV1.2 calcium channel clusters is
      independent of interactions with AKAP79/150 and PDZ proteins.
AB  - In neurons L-type calcium currents contribute to synaptic plasticity and to
      activity-dependent gene regulation. The subcellular localization of Ca(V)1.2 and
      its association with upstream and downstream signaling proteins is important for
      efficient and specific signal transduction. Here we tested the hypothesis that A
      kinase anchoring proteins (AKAPs) or PDZ-proteins are responsible for the
      targeting and anchoring of Ca(V)1.2 in the postsynaptic compartment of
      glutamatergic neurons. Double-immunofluorescence labeling of hippocampal neurons
      transfected with external HA epitope-tagged Ca(V)1.2 demonstrated that clusters
      of membrane-incorporated Ca(V)1.2-HA were colocalized with AKAP79/150 but not
      with PSD-95 in the spines and shafts of dendrites. To disrupt the interactions
      with these scaffold proteins, we mutated known binding sequences for AKAP79/150
      and PDZ proteins in the C terminus of Ca(V)1.2-HA. Unexpectedly, the distribution
      pattern, the density, and the fluorescence intensity of clusters were similar for
      wild-type and mutant Ca(V)1.2-HA, indicating that interactions with AKAP and PDZ
      proteins are not essential for the correct targeting of Ca(V)1.2. In agreement,
      brief treatment with NMDA (a chemical LTD paradigm) caused the degradation of PSD
      95 and the redistribution of AKAP79/150 and alpha-actinin from dendritic spines
      into the shaft, without a concurrent loss or redistribution of Ca(V)1.2-HA
      clusters. Thus, in the postsynaptic compartment of hippocampal neurons Ca(V)1.2
      calcium channels form signaling complexes apart from those of glutamate receptors
      and PSD-95. Their number and distribution in dendritic spines is not altered upon
      NMDA-induced disruption of the glutamate receptor signaling complex, and
      targeting and anchoring of Ca(V)1.2 is independent of its interactions with
      AKAP79/150 and PDZ proteins.

PMID- 19091976
TI  - Effects of prior information and reward on oculomotor and perceptual choices.
AB  - Expectations about the environment influence motor behavior. In simple tasks, for
      example, prior knowledge about which stimulus event will likely occur or which
      response will likely be rewarded induces a tendency to take the favored action
      (i.e., a motor or response bias), especially when sensory information is sparse
      or ambiguous. Models of choice behavior account for this bias by weighting
      decision alternatives unequally, either at an early sensory-input stage or at a
      downstream motor-output stage. These two alternatives can be distinguished
      empirically; the former predicts an altered percept that correlates with motor
      bias, the latter predicts no perceptual effect. By varying the prior probability
      of target or reward location, we induced biased oculomotor responses in a
      brightness selection task with human subjects. We found that the induced motor
      bias was correlated with an amplification of both the sensory signals and
      internal noise underlying brightness perception, without a systematic change in
      perceived overall brightness. We also found that the magnitude of the sensory
      amplification was correlated with the amount of noise in the brightness percept,
      consistent with a multiplicative weighting factor located downstream from the
      limiting internal sensory noise. Our data demonstrate that prior knowledge (about
      target location or reward) shapes visual signals for perception and action in
      parallel but does not improve the quality (i.e., signal-to-noise ratio) of
      sensory processing.

PMID- 19091975
TI  - Dopamine enhances fast excitatory synaptic transmission in the extended amygdala
      by a CRF-R1-dependent process.
AB  - A common feature of drugs of abuse is their ability to increase extracellular
      dopamine levels in key brain circuits. The actions of dopamine within these
      circuits are thought to be important in reward and addiction-related behaviors.
      Current theories of addiction also posit a central role for corticotrophin
      releasing factor (CRF) and an interaction between CRF and monoaminergic
      signaling. One region where drugs of abuse promote robust rises in extracellular
      dopamine levels is the bed nucleus of the stria terminalis (BNST), a CRF-rich
      component of the extended amygdala. We find that dopamine rapidly enhances
      glutamatergic transmission in the BNST through activation of a combination of
      D(1)- and D(2)-like receptors. This enhancement is activity-dependent and
      requires the downstream action of CRF receptor 1 (CRF-R1), suggesting that
      dopamine induces CRF release through a local network mechanism. Furthermore, we
      found that both in vivo and ex vivo cocaine induced a dopamine receptor and CRF
      R1-dependent enhancement of a form of NMDA receptor-dependent short-term
      potentiation in the BNST. These data highlight a direct and rapid interaction
      between dopamine and CRF systems that regulates excitatory transmission and
      plasticity in a brain region key to reinforcement and reinstatement. Because a
      rise in extracellular dopamine levels in the BNST is a shared consequence of
      multiple classes of drugs of abuse, this suggests that the CRF-R1-dependent
      enhancement of glutamatergic transmission in this region may be a common key
      feature of substances of abuse.

PMID- 19091978
TI  - Stimulus dependency and mechanisms of surround modulation in cortical area MT.
AB  - The perceptual interpretation of a given visual feature depends on the
      surrounding context. To explore the neural mechanisms underlying such contextual
      interactions in the motion domain, we studied responses of neurons in the middle
      temporal area (MT) of macaque monkeys while presenting a variety of center
      surround stimuli that stimulated both the classical receptive visual field (CRF)
      and the receptive field surround. In human psychophysical experiments, the
      perceptual impact of the surround stimulus on the center stimulus varied from
      motion capture ("integration") to motion contrast ("segmentation"). In our
      neurophysiological experiments, the directional tuning of surround modulation
      with these stimuli ranged from antagonistic (consistent with motion contrast) to
      integrative (consistent with motion capture) and agreed qualitatively with
      perception under some but not all conditions. Most strikingly, for a stimulus
      that elicited perceptual motion contrast, surround modulation was integrative if
      the CRF stimulus was ambiguous due to the aperture problem. In addition, we found
      that surround modulation was linked to response magnitude: stimuli eliciting the
      largest responses yielded the strongest antagonism and those eliciting the
      smallest responses yielded the strongest integration. We developed a neural
      network model that accounts for this finding as well as a previous finding that
      surround suppression in area MT is contrast-dependent. Our findings suggest that
      changes in MT surround modulation result from shifts in the balance between
      directionally tuned excitation and inhibition mediated by changes in input
      strength. We speculate that input strength is, in turn, linked with the ambiguity
      of the motion present within the CRF.

PMID- 19091979
TI  - Prenatal to early postnatal nicotine exposure impairs central chemoreception and
      modifies breathing pattern in mouse neonates: a probable link to sudden infant
      death syndrome.
AB  - Nicotine is a neuroteratogen and is the likely link between maternal cigarette
      smoking during pregnancy and sudden infant death syndrome (SIDS). Osmotic
      minipumps were implanted in 5-7 d CF1 pregnant mice to deliver nicotine
      bitartrate (60 mg Kg(-1) day(-1)) or saline (control) solutions for up to 28 d.
      Prenatal to early postnatal nicotine exposure did not modify the number of
      newborns per litter or their postnatal growth; however, nicotine-exposed neonates
      hypoventilated and had reduced responses to hypercarbia (inhalation of air
      enriched with 10% CO(2) for 20 min) and hypoxia (inhalation of 100% N(2) for 20
      s) at postnatal days 0-3 (P0-P3). In contrast, at postnatal day 8, nicotine
      exposed neonates were indistinguishable from controls. Isolated brainstem-spinal
      cord preparations obtained from P0 to P3 nicotine-exposed neonates showed fictive
      respiration with respiratory cycles longer and more irregular than those of
      controls, as indicated by high short- and long-term variability in Poincare
      plots. In addition, their responses to acidification were reduced, indicating
      compromise of central chemoreception. Furthermore, the cholinergic contribution
      to central chemosensory responses switched from muscarinic receptor to nicotinic
      receptor-based mechanisms. No significant astrogliosis was detectable in the
      ventral respiratory group of neurons with glial fibrillary acidic protein
      immunohistochemistry. These results indicate that nicotine exposure affects the
      respiratory rhythm pattern generator and causes a decline in central
      chemoreception during early postnatal life. Consequently, breathing would become
      highly vulnerable, failing to respond to chemosensory demands. Such impairment
      could be related to the ventilatory abnormalities observed in SIDS.

PMID- 19091977
TI  - Deficiency in complement C1q improves histological and functional locomotor
      outcome after spinal cord injury.
AB  - Although studies have suggested a role for the complement system in the
      pathophysiology of spinal cord injury (SCI), that role remains poorly defined.
      Additionally, the relative contribution of individual complement pathways in SCI
      is unknown. Our initial studies revealed that systemic complement activation was
      strongly influenced by genetic background and gender. Thus, to investigate the
      role of the classical complement pathway in contusion-induced SCI, male C1q knock
      out (KO) and wild-type (WT) mice on a complement sufficient background (BUB)
      received a mild-moderate T9 contusion injury with the Infinite Horizon impactor.
      BUB C1q KO mice exhibited greater locomotor recovery compared with BUB WT mice
      (p<0.05). Improved recovery observed in BUB C1q KO mice was also associated with
      decreased threshold for withdrawal from a mild stimulus using von Frey filament
      testing. Surprisingly, quantification of microglia/macrophages (F4/80) by FACS
      analysis showed that BUB C1q KO mice exhibited a significantly greater percentage
      of macrophages in the spinal cord compared with BUB WT mice 3 d post-injury
      (p<0.05). However, this increased macrophage response appeared to be transient as
      stereological assessment of spinal cord tissue obtained 28 d post-injury revealed
      no difference in F4/80-positive cells between groups. Stereological assessment of
      spinal cord tissue showed that BUB C1q KO mice had reduced lesion volume and an
      increase in tissue sparing compared with BUB WT mice (p<0.05). Together, these
      data suggest that initiation of the classical complement pathway via C1q is
      detrimental to recovery after SCI.

PMID- 19091981
TI  - Changes in control of saccades during gain adaptation.
AB  - In a typical short-term saccadic adaptation protocol, the target moves
      intrasaccadically either toward (gain-down) or away (gain-up) from initial
      fixation, causing the saccade to complete with an endpoint error. A central
      question is how the motor system adapts in response to this error: are the motor
      commands changed to bring the eyes to a different goal, akin to a remapping of
      the target, or is adaptation focused on the processes that monitor the ongoing
      motor commands and correct them midflight, akin to changes that act via internal
      feedback? Here, we found that, in the gain-down paradigm, the brain learned to
      produce a smaller amplitude saccade by altering the trajectory of the saccade.
      The adapted saccades had reduced peak velocities, reduced accelerations,
      shallower decelerations, and increased durations compared with a control saccade
      of equal amplitude. These changes were consistent with a change in an internal
      feedback that acted as a forward model. However, in the gain-up paradigm, the
      brain learned to produce a larger amplitude saccade with trajectories that were
      identical with those of control saccades of equal amplitude. Therefore, whereas
      the gain-down paradigm appeared to induce adaptation via an internal feedback
      that controlled saccades midflight, the gain-up paradigm induced adaptation
      primarily via target remapping. Our simulations explained that, for each
      condition, the specific adaptation produced a saccade that brought the eyes to
      the target with the smallest motor costs.

PMID- 19091980
TI  - Sequential changes in AMPA receptor targeting in the developing neocortical
      excitatory circuit.
AB  - Many principal neurons undergo an early developmental switch from GluR2-lacking
      to GluR2-containing synaptic glutamate receptors. We tested the generality and
      timing of the GluR2 switch in excitatory neurons of rat somatosensory cortex.
      Previous studies show that the switch occurs between postnatal day 14 (P14) and
      P16 in layer 5 pyramidal neurons. We show, using sensitivity to intracellular
      spermine, that a similar switch occurs between P12 and P14 in layer 2/3 pyramidal
      cells and between P7 and P8 in layer 4 stellate cells. The presence of GluR2
      lacking receptors in layer 2/3 pyramidal cells before P12 was confirmed by
      demonstrating sensitivity to blockade by 1-naphthyl-acetyl-spermine and large
      single-channel conductances. GluR2 and the postsynaptic protein PSD95 show
      progressive colocalization in tissue from P10, P14, and P24 rats, mirroring
      electrophysiological developments. To distinguish whether changes in GluR2
      expression or targeting underlie the switch, we characterized dendritic AMPA
      receptor responses using focal photolysis of caged glutamate. Contrary to
      synaptic responses, dendritic responses at all ages studied (P6-P40) were
      characteristic of GluR2-containing receptors. In addition, dendritically and
      synaptically evoked responses showed a corresponding decrease in NMDA/AMPA ratios
      in pyramidal cells, suggesting parallel mechanisms that regulate neuronal calcium
      levels. These data suggest that the GluR2 switch results from changes in AMPA
      receptor targeting during early postnatal development, and that rather than
      following the laminar sequence of cortical development, it proceeds sequentially
      from layer 4 to layer 2/3 and finally to layer 5b.

PMID- 19091982
TI  - Hereditary spastic paraplegia-associated mutations in the NIPA1 gene and its
      Caenorhabditis elegans homolog trigger neural degeneration in vitro and in vivo
      through a gain-of-function mechanism.
AB  - We studied the consequences of expression of wild-type (WT) human NIPA1 and two
      mutant forms of NIPA1 with known HSP-associated mutations (T45R and G106R) on
      cultured rat cortical neurons and using equivalent substitutions in the
      Caenorhabditis elegans NIPA1 homolog CeNIPA. WT NIPA1 localized in transfected
      neuronal and non-neuronal cells to the Golgi complex, a subset of synaptic
      vesicles, to a subset of early endosomes, and plasma cell membrane. Mutant NIPA1
      accumulated in the endoplasmic reticulum (ER) triggering ER stress and features
      of apoptotic cell death. Flow cytometric analysis of NIPA1 surface expression
      demonstrated relatively intact trafficking of mutant forms and only the T45R
      mutant exhibited modestly reduced patterns of surface expression without evidence
      for a dominant-negative effect. In vivo pan-neuronal expression of the WT C.
      elegans NIPA1 homolog (CeNIPA) was well tolerated, with no obvious impact on
      neuronal morphology or behavior. In striking contrast, expression of CeNIPA
      bearing HSP-associated mutations caused a progressive neural degeneration and a
      clear motor phenotype. Neuronal loss in these animals began at day 7 and by day 9
      animals were completely paralyzed. These effects appeared to arise from
      activation of the apoptotic program triggered by unfolded protein response (UPR),
      as we observed marked modifications of motor and cellular phenotype when mutant
      NIPA1 was expressed in caspase (ced-3)- and UPR (xbp-1)-deficient backgrounds. We
      propose that HSP-associated mutations in NIPA1 lead to cellular and functional
      deficits through a gain-of-function mechanism supporting the ER accumulation of
      toxic NIPA1 proteins.

PMID- 19091983
TI  - Chronic Galphas signaling in the striatum increases anxiety-related behaviors
      independent of developmental effects.
AB  - Current research in the field of anxiety disorders is largely receptor-centric,
      leaving intracellular pathways largely unexplored. Galphas, the G-protein which
      stimulates adenylyl cyclase and L-type voltage-gated calcium channels, may be one
      intracellular molecule regulating anxiety-related behaviors as increased efficacy
      of Galphas signaling has been noted in patient populations that suffer from
      anxiety. We report here anxiety-related behaviors in two lines of transgenic mice
      expressing a constitutively active isoform of Galphas (or Galphas*). The first
      line expressed Galphas* throughout postnatal forebrain neurons, while the second
      line of mice conditionally expressed Galphas* selectively in the striatum
      (Galphas*(str) mice). In the open field, both lines of mice showed a significant
      preference for the periphery suggesting that expression of Galphas* in the
      striatum alone was sufficient to produce an anxiogenic phenotype. In the
      light/dark box, Galphas*(str) mice exhibited longer latencies to enter the light
      and spent significantly less time in the lit compartment. Similarly,
      Galphas*(str) mice showed longer latencies to enter the open quadrants and spent
      less time in the open quadrants of the elevated zero maze. Interestingly, these
      anxiety-related phenotypes were largely unrelated to developmental effects as
      mice expressing the Galphas*(str) transgene during development, but not at
      testing, were normal on most measures. These observations show that chronic
      Galphas signaling in the striatum is sufficient to trigger anxiety-related
      behaviors largely independent of developmental effects and suggest the cAMP
      pathway or L-type voltage-gated calcium channels may be viable targets for future
      pharmacological intervention in the treatment of anxiety disorders.

PMID- 19091984
TI  - Interleukin-6 mediates the increase in NADPH-oxidase in the ketamine model of
      schizophrenia.
AB  - Adult exposure to NMDA receptor antagonists, such as ketamine, produces psychosis
      in humans, and exacerbates symptoms in schizophrenic patients. We recently showed
      that ketamine activates the innate immune enzyme NADPH-oxidase in brain, and that
      the superoxide produced leads to dysfunction of a subset of fast-spiking
      inhibitory interneurons expressing the calcium-binding protein parvalbumin (PV).
      Here we show that neuronal production of interleukin-6 (IL-6) is necessary and
      sufficient for ketamine-mediated activation of NADPH-oxidase in brain. Removal of
      IL-6 in neuronal cultures by anti-IL-6 blocking antibodies, or in vivo by use of
      IL-6-deficient mice, prevented the increase in superoxide by ketamine and rescued
      the interneurons. Accumulating evidence suggests that schizophrenia patients
      suffer from diminished antioxidant defenses, and a recent clinical trial showed
      that enhancing these defenses may ameliorate symptoms of the disease. Our results
      showing that ketamine-induced IL-6 is responsible for the activation of NADPH
      oxidase in brain suggest that reducing brain levels of this cytokine may protect
      the GABAergic phenotype of fast-spiking PV-interneurons and thus attenuate the
      propsychotic effects of ketamine.

PMID- 19091985
TI  - Cortically evoked long-lasting inhibition of pallidal neurons in a transgenic
      mouse model of dystonia.
AB  - Dystonia is a neurological disorder characterized by sustained or repetitive
      involuntary muscle contractions and abnormal postures. To understand the
      pathophysiology of dystonia, neurophysiological analyses were performed on
      hyperkinetic transgenic mice generated as a model of DYT1 dystonia. Abnormal
      muscle activity, such as coactivation of agonist and antagonist muscles and
      sustained muscle activation, was frequently observed in these mice. Recording of
      neuronal activity in the awake state revealed reduced spontaneous activity with
      bursts and pauses in both the external and internal segments of the globus
      pallidus. Motor cortical stimulation evoked responses composed of excitation and
      subsequent long-lasting inhibition in both pallidal segments, which were never
      observed in the normal mice. In addition, the somatotopic arrangements in both
      pallidal segments were disorganized. Long-lasting inhibition induced by cortical
      inputs in the internal pallidal segment may disinhibit thalamic and cortical
      activity, resulting in the motor hyperactivity observed in the transgenic mice.

PMID- 19091986
TI  - Toll-like receptor 3 is a negative regulator of embryonic neural progenitor cell
      proliferation.
AB  - Toll-like receptors (TLRs) play important roles in innate immunity. Several TLR
      family members have recently been shown to be expressed by neurons and glial
      cells in the adult brain, and may mediate responses of these cells to injury and
      infection. To address the possibility that TLRs play a functional role in
      development of the nervous system, we analyzed the expression of TLRs during
      different stages of mouse brain development and assessed the role of TLRs in cell
      proliferation. TLR3 protein is present in brain cells in early embryonic stages
      of development, and in cultured neural stem/progenitor cells (NPC). NPC from TLR3
      deficient embryos formed greater numbers of neurospheres compared with
      neurospheres from wild-type embryos. Numbers of proliferating cells, as assessed
      by phospho histone H3 and proliferating cell nuclear antigen labeling, were also
      increased in the developing cortex of TLR3-deficient mice compared with wild-type
      mice in vivo. Treatment of cultured embryonic cortical neurospheres with a TLR3
      ligand (polyIC) significantly reduced proliferating (BrdU-labeled) cells and
      neurosphere formation in wild type but not TLR3(-/-)-derived NPCs. Our findings
      reveal a novel role for TLR3 in the negative regulation of NPC proliferation in
      the developing brain.

PMID- 19091988
TI  - Enhanced plasticity in zincergic, cortical circuits after exposure to enriched
      environments.
AB  - Despite the plethora of reports that demonstrate plasticity in the mammalian
      cerebral cortex, the characterization of the cellular mechanisms that mediate it
      is sparse. Here, we show that the magnitude of the experience-dependent
      regulation of vesicular zinc is significantly increased through enriched
      environment housing. Mice were reared either in a deprived environment and
      subsequently housed in deprived, minimally enriched, or enriched conditions after
      the removal of the c-row of vibrissae or reared in an enriched environment before
      and after vibrissae removal. Levels of vesicular zinc were assessed in deprived
      and nondeprived barrels 6 h to 14 d after vibrissae removal. We found that
      housing in enriched environmental conditions resulted in a greater change in
      vesicular zinc levels than did other housing conditions; however, this effect was
      dependent on both the magnitude and duration of enrichment. Our data indicate
      that enriched-environment housing has profound effects on the regulation of
      vesicular zinc that occurs concurrently with experience-dependent plasticity,
      suggesting a role for zinc in the multitude of cortical modifications associated
      with enriched environments.

PMID- 19091987
TI  - Endogenous fatty acid ethanolamides suppress nicotine-induced activation of
      mesolimbic dopamine neurons through nuclear receptors.
AB  - Nicotine stimulates the activity of mesolimbic dopamine neurons, which is
      believed to mediate the rewarding and addictive properties of tobacco use.
      Accumulating evidence suggests that the endocannabinoid system might play a major
      role in neuronal mechanisms underlying the rewarding properties of drugs of
      abuse, including nicotine. Here, we investigated the modulation of nicotine
      effects by the endocannabinoid system on dopamine neurons in the ventral
      tegmental area with electrophysiological techniques in vivo and in vitro. We
      discovered that pharmacological inhibition of fatty acid amide hydrolase (FAAH),
      the enzyme that catabolizes fatty acid ethanolamides, among which the
      endocannabinoid anandamide (AEA) is the best known, suppressed nicotine-induced
      excitation of dopamine cells. Importantly, this effect was mimicked by the
      administration of the FAAH substrates oleoylethanolamide (OEA) and
      palmitoylethanolamide (PEA), but not methanandamide, the hydrolysis resistant
      analog of AEA. OEA and PEA are naturally occurring lipid signaling molecules
      structurally related to AEA, but devoid of affinity for cannabinoid receptors.
      They blocked the effects of nicotine by activation of the peroxisome proliferator
      activated receptor-alpha (PPAR-alpha), a nuclear receptor transcription factor
      involved in several aspects of lipid metabolism and energy balance. Activation of
      PPAR-alpha triggered a nongenomic stimulation of tyrosine kinases, which might
      lead to phosphorylation and negative regulation of neuronal nicotinic
      acetylcholine receptors. These data indicate for the first time that the anorexic
      lipids OEA and PEA possess neuromodulatory properties as endogenous ligands of
      PPAR-alpha in the brain and provide a potential new target for the treatment of
      nicotine addiction.

PMID- 19091989
TI  - Dorsal medial prefrontal cortex plays a necessary role in rapid error prediction
      in humans.
AB  - Activity in human dorsal anterior cingulate cortex (dACC) is correlated with
      errors, near-misses, and response conflict. Based on these observations, this
      region has been cast as playing a central role in models of error processing,
      conflict monitoring, and cognitive control. However, clear evidence that this
      region of the brain is necessary for these processes has been elusive. We studied
      the effects of damage to this region on four different error-related measures in
      five patients, and 19 healthy participants. Most error-related indices were not
      affected by such damage: patients had intact post-error slowing, and were able to
      report and to correct errors after they were made with accuracies comparable with
      the control group. However, all five patients were notably slow to correct
      errors, suggesting a deficit in on-line error prediction. This slowing was
      associated with impairment in the conscious prediction of error likelihood before
      a response. This finding constitutes important converging evidence for a critical
      role for human dACC in error monitoring, and sheds light on the selectivity and
      timing of the error-related process affected by dACC damage.

PMID- 19091990
TI  - Immunogenicity of a reduced schedule of meningococcal group C conjugate vaccine
      given concomitantly with the Prevenar and Pediacel vaccines in healthy infants in
      the United Kingdom.
AB  - This study investigated the use of two doses of three different meningococcal
      group C conjugate (MCC) vaccines when given for primary immunization with a seven
      valent pneumococcal conjugate vaccine (PCV7) and Pediacel, a combination product
      containing five acellular pertussis components, diphtheria and tetanus toxoids,
      Haemophilus influenzae type b (Hib) conjugate, and inactivated-poliovirus
      vaccine. The immune response after a single dose of MCC is also presented.
      Infants were randomized to receive two doses of one of the MCC vaccines and PCV7
      at 2 and 3 months or at 2 and 4 months of age. Meningococcal group C serum
      bactericidal antibody (SBA) geometric mean titers, Hib-polyribosylribitol
      phosphate (PRP) immunoglobulin G (IgG) geometric mean concentrations (GMCs), and
      diphtheria and tetanus antitoxin GMCs, together with the proportions of infants
      achieving putative protective levels, were determined. A total of 393 infants
      were recruited. Following the first dose of NeisVac-C (MCC conjugated to tetanus
      toxoid), 97% of infants achieved protective levels (SBA titer of >or=8), compared
      with 80% and 53%, respectively, for Menjugate and Meningitec (both of which are
      conjugated to CRM(197)). SBA responses to MCC vaccines were not significantly
      different when administered at 2 and 3 or 2 and 4 months of age. Following two
      doses of each MCC, 98 to 100% of infants achieved protective levels. Both PRP IgG
      and tetanus responses were significantly enhanced when Pediacel was
      coadministered with NeisVac-C. This study demonstrates that NeisVac-C and
      Menjugate generate good immunogenicity after the first dose at 2 months of age
      when coadministered with PCV7 and Pediacel and merit further investigation in
      single-dose priming strategies.

PMID- 19091991
TI  - Concordant proficiency in measurement of T-cell immunity in human
      immunodeficiency virus vaccine clinical trials by peripheral blood mononuclear
      cell and enzyme-linked immunospot assays in laboratories from three continents.
AB  - The gamma interferon (IFN-gamma) enzyme-linked immunospot (ELISPOT) assay is used
      routinely to evaluate the potency of human immunodeficiency virus (HIV) vaccine
      candidates and other vaccine candidates. In order to compare candidates and pool
      data from multiple trial laboratories, validated standardized methods must be
      applied across laboratories. Proficiency panels are a key part of a comprehensive
      quality assurance program to monitor inter- and intralaboratory performance, as
      well as assay performance, over time. Seven International AIDS Vaccine Initiative
      sponsored trial sites participated in the proficiency panels described in this
      study. At each laboratory, two operators independently processed identical sample
      sets consisting of frozen peripheral blood mononuclear cell (PBMC) samples from
      different donors by using four blind stimuli. PBMC recovery and viability after
      overnight resting and the IFN-gamma ELISPOT assay performance were assessed. All
      sites demonstrated good performance in PBMC thawing and resting, with a median
      recovery of 78% and median viability of 95%. The laboratories were able to detect
      similar antigen-specific T-cell responses, ranging from 50 to >3,000 spot-forming
      cells per million PBMC. An approximate range of a half log in results from
      operators within or across sites was seen in comparisons of antigen-specific
      responses. Consistently low background responses were seen in all laboratories.
      The results of these proficiency panels demonstrate the ability of seven
      laboratories, located across three continents, to process PBMC samples and to
      rank volunteers with differential magnitudes of IFN-gamma ELISPOT responses.
      These findings also illustrate the ability to standardize the IFN-gamma ELISPOT
      assay across multiple laboratories when common training methods, reagents such as
      fetal calf serum, and standard operating procedures are adopted. These results
      are encouraging for laboratories that are using cell-based immunology assays to
      test HIV vaccines and other vaccines.

PMID- 19091992
TI  - Protection against Asiatic Taenia solium induced by a recombinant 45W-4B protein.
AB  - Taenia solium is a great threat not only to human health but also to the pig
      raising industry. Oncospheral stage-specific 45W proteins are good candidates for
      the development of anticysticercosis vaccines. In this study, a recombinant 45W
      4B protein was highly produced and used for vaccination. Two animal trials
      resulted in a significant reduction in parasite burden induced by the definite
      protein against Asiatic T. solium, up to 97.0% and 98.4%, respectively. These
      provide informative results for the development of effective 45W-4B vaccines
      against cysticercosis caused by both Chinese and Mexican T. solium isolates and
      even by other isolates.

PMID- 19091993
TI  - Generation of immune responses against hepatitis C virus by dendritic cells
      containing NS5 protein-coated microparticles.
AB  - Dendritic cells (DCs) internalize and process antigens as well as activate
      cellular immune responses. The aim of this study was to determine the capacity of
      DCs that contain antigen-coated magnetic beads to induce immunity against the
      nonstructural hepatitis C virus (HCV) antigen 5 (NS5). Splenocytes derived from
      Fms-like tyrosine kinase receptor 3 (Flt3) ligand-pretreated BALB/c mice were
      incubated with magnetic beads coated with HCV NS5, lipopolysaccharide (LPS),
      and/or anti-CD40; purified; and used for immunization. Cellular immunity was
      measured using cytotoxic T-lymphocyte (CTL) and T-cell proliferation assays,
      intracellular cytokine staining, and a syngeneic tumor challenge using NS5
      expressing SP2/0 myeloma cells in vivo. Splenocytes isolated from animals
      vaccinated with DCs containing beads coated with NS5, LPS, and anti-CD40 secreted
      elevated levels of interleukin-2 (IL-2) and gamma interferon in the presence of
      NS5. The numbers of CD4(+), IL-2-producing cells were increased >5-fold in the
      group immunized with DCs containing beads coated with NS5, LPS, and anti-CD40,
      paralleled by an enhanced splenocyte proliferative response. Immunization
      promoted antigen-specific CTL activity threefold compared to the level for
      control mice and significantly reduced the growth of NS5-expressing tumor cells
      in vivo. Thus, strategies that employ NS5-coated beads induce cellular immune
      responses in mice, which correlate well with the natural immune responses that
      occur in individuals who resolve HCV.

PMID- 19091994
TI  - Heightened cytotoxic responses and impaired biogenesis contribute to early
      pathogenesis in the oral mucosa of simian immunodeficiency virus-infected rhesus
      macaques.
AB  - Simian immunodeficiency virus (SIV) infection disseminated into the oropharyngeal
      tissues of rhesus macaques 6 weeks following intravenous inoculation. Severe
      local CD4(+) T-cell depletion coincided with increases in NK cell and
      proinflammatory biomarkers and the disruption of growth-associated gene
      transcription, demonstrating the rapid establishment of pathogenesis in the oral
      mucosa.

PMID- 19091995
TI  - Age-specific cluster of cases of serotype 1 Streptococcus pneumoniae carriage in
      remote indigenous communities in Australia.
AB  - Seven-valent pneumococcal conjugate vaccination commenced in 2001 for Australian
      indigenous infants. Pneumococcal carriage surveillance detected substantial
      replacement with nonvaccine serotypes and a cluster of serotype 1 carriage. Our
      aim was to review Streptococcus pneumoniae serotype 1 carriage and invasive
      pneumococcal disease (IPD) data for this population and to analyze serotype 1
      isolates. Carriage data were collected between 1992 and 2004 in the Darwin
      region, one of the five regions in the Northern Territory. Carriage data were
      also collected in 2003 and 2005 from four regions in the Northern Territory.
      Twenty-six cases of serotype 1 IPD were reported from 1994 to 2007 in the
      Northern Territory. Forty-four isolates were analyzed by BOX typing and 11 by
      multilocus sequence typing. In the Darwin region, 26 children were reported
      carrying serotype 1 (ST227) in 2002 but not during later surveillance. Scattered
      cases of serotype 1 carriage were noted in two other regions. Cocolonization of
      serotype 1 with other pneumococcal serotypes was common (34% serotype 1-positive
      swabs). In conclusion, pneumococcal carriage studies detected intermittent
      serotype 1 carriage and an ST227 cluster in children in indigenous communities in
      the Northern Territory of Australia. There was no apparent increase in serotype 1
      IPD during this time. The rate of serotype 1 cocolonization with other
      pneumococcal serotypes suggests that carriage of this serotype may be
      underestimated.

PMID- 19091997
TI  - Surgical aspects of the diabetic foot.
AB  - A comprehensive review of the literature relating to the pathology and management
      of the diabetic foot is presented. This should provide a guide for the treatment
      of ulcers, Charcot neuro-arthropathy and fractures involving the foot and ankle
      in diabetic patients.

PMID- 19091996
TI  - Competitive inhibition flow analysis assay for the non-culture-based detection
      and serotyping of pneumococcal capsular polysaccharide.
AB  - Traditional confirmation procedures for the identification of a pneumococcal
      serotype require an isolate. Non-culture-based confirmation protocols are
      available. Some of these confirm only the presence of pneumococci, and others are
      capable of identifying a limited number of serotypes. The increased use of
      pneumococcal polysaccharide and conjugate vaccines, especially in high-risk
      patient groups, and the likely increase in the number of serotypes included in
      future versions of the conjugate vaccines have necessitated the need for improved
      enhanced surveillance in order to assess their impact on public health. Since
      2006, a multiplexed assay has been used at the Health Protection Agency of the
      United Kingdom for the detection of 14 pneumococcal serotypes which requires
      pneumococcal serotype-specific monoclonal antibodies (MAbs). We have developed a
      microsphere competitive inhibition method capable of detecting 23 pneumococcal
      capsular polysaccharide serotypes in cerebrospinal fluid (CSF) and urine and
      serotyping pneumococcal suspensions, utilizing an international reference serum,
      89-SF. The assay was shown to be reproducible and specific for homologous
      polysaccharide. Validation of the assay was performed with a selection of MAbs
      specific for pneumococcal capsular polysaccharide serotypes, which confirmed the
      specificity of the assay. Analysis of pneumolysin PCR-positive CSF samples in the
      competitive inhibition assay determined a serotype for 89% of the samples. The
      assay developed here is well suited to large-scale epidemiologic studies because
      the assay is simple, robust, and rapid and utilizes readily available resources.

PMID- 19091998
TI  - The ligamentum teres of the adult hip.
AB  - Advances in hip arthroscopy have renewed interest in the ligamentum teres.
      Considered by many to be a developmental vestige, it is now recognised as a
      significant potential source of pain and mechanical symptoms arising from the hip
      joint. Despite improvements in imaging, arthroscopy remains the optimum method of
      diagnosing lesions of the ligamentum teres. Several biological or mechanical
      roles have been proposed for the ligament. Unless these are disproved, the use of
      surgical procedures that sacrifice the ligamentum teres, as in surgical
      dislocation of the hip, should be carefully considered. This paper provides an
      update on the development, structure and function of the ligamentum teres, and
      discusses associated clinical implications.

PMID- 19091999
TI  - Outcomes following hip arthroscopy for femoroacetabular impingement with
      associated chondrolabral dysfunction: minimum two-year follow-up.
AB  - Over an eight-month period we prospectively enrolled 122 patients who underwent
      arthroscopic surgery of the hip for femoroacetabular impingement and met the
      inclusion criteria for this study. Patients with bilateral hip arthroscopy,
      avascular necrosis and previous hip surgery were excluded. Ten patients refused
      to participate leaving 112 in the study. There were 62 women and 50 men. The mean
      age of the patients was 40.6 yrs (95% confidence interval (CI) 37.7 to 43.5). At
      arthroscopy, 23 patients underwent osteoplasty only for cam impingement, three
      underwent rim trimming only for pincer impingement, and 86 underwent both
      procedures for mixed-type impingement. The mean follow-up was 2.3 years (2.0 to
      2.9). The mean modified Harris hip score (HHS) improved from 58 to 84 (mean
      difference = 24 (95% CI 19 to 28)) and the median patient satisfaction was 9 (1
      to 10). Ten patients underwent total hip replacement at a mean of 16 months (8 to
      26) after arthroscopy. The predictors of a better outcome were the pre-operative
      modified HHS (p = 0.018), joint space narrowing >or= 2 mm (p = 0.005), and repair
      of labral pathology instead of debridement (p = 0.032). Hip arthroscopy for
      femoroacetabular impingement, accompanied by suitable rehabilitation, gives a
      good short-term outcome and high patient satisfaction.

PMID- 19092000
TI  - The Long Oblique Revision component in revision arthroplasty of the hip.
AB  - Migration of the acetabular component may give rise to oval-shaped bone defects
      in the acetabulum. The oblong implant is designed to fill these defects and
      achieve a stable cementless anchorage with no significant bone loss. We
      prospectively reviewed 133 oblong long oblique revision components at a mean
      follow-up of 9.74 years (0.6 to 14). All had been used in revisions for defects
      of type IIB to IIIB according to Paprosky. Aseptic loosening was the reason for
      revision in 11 cases (8.3%) and deep infection in seven (5.3%). The probability
      of implant survival over a 12-year follow-up estimated by the Kaplan-Meier method
      gave a survival rate of 0.85% respectively 0.90% when deep infection was excluded
      as the endpoint. Our study supports the use of these components in defects from
      IIB to IIIA. The main precondition for success is direct contact of more than
      half of the surface of the implant with the host acetabular bone.

PMID- 19092001
TI  - The long-term outcome of the cemented Weber acetabular component in total hip
      replacement using a second-generation cementing technique.
AB  - We report the long-term outcome of a modified second-generation cementing
      technique for fixation of the acetabular component of total hip replacement. An
      earlier report has shown the superiority of this technique assessed by improved
      survival compared with first-generation cementing. The acetabular preparation
      involved reaming only to the subchondral plate, followed by impaction of the bone
      in the anchorage holes. Between 1978 and 1993, 287 total hip replacements were
      undertaken in 244 patients with a mean age of 65.3 years (21 to 90) using a
      hemispherical Weber acetabular component with this modified technique for
      cementing and a cemented femoral component. The survival with acetabular revision
      for aseptic loosening as the endpoint was 99.1% (95% confidence interval 97.9 to
      100 after ten years and 85.5% (95% confidence interval 74.7 to 96.2) at 20 years.
      Apart from contributing to a long-lasting fixation of the component, this
      technique also preserved bone, facilitating revision surgery when necessary.

PMID- 19092002
TI  - Subsidence of the stem after impaction bone grafting for revision hip replacement
      using irradiated bone.
AB  - Loss of bone stock is a major problem in revision surgery of the hip. Impaction
      bone grafting of the femur is frequently used when dealing with deficient bone
      stock. In this retrospective study a consecutive series of 68 patients (69 hips)
      who had revision of a hip replacement with femoral impaction grafting were
      reviewed. Irradiated bone allograft was used in all hips. Radiological
      measurement of subsidence of the stem, incorporation of the graft and remodelling
      was carried out and showed incorporation of the graft in 26 of 69 hips (38%).
      However, there was no evidence of trabecular remodelling. Moderate subsidence of
      5 mm to 10 mm occurred in ten hips (14.5%), and massive subsidence of > 10 mm in
      five (7.2%). The results of this study are less favourable than those of others
      describing studies of revision of the femoral stem using impaction bone grafting.
      The absence of the characteristic changes of graft remodelling noted in other
      series raises the question as to whether irradiated bone graft may be a
      significant factor influencing the post-operative outcome.

PMID- 19092003
TI  - Is prolonged systemic antibiotic treatment essential in two-stage revision hip
      replacement for chronic Gram-positive infection?
AB  - When using a staged approach to eradicate chronic infection after total hip
      replacement, systemic delivery of antibiotics after the first stage is often
      employed for an extended period of typically six weeks together with the use of
      an in situ antibiotic-eluting polymethylmethacrylate interval spacer. We report
      our multi-surgeon experience of 43 consecutive patients (44 hips) who received
      systemic vancomycin for two weeks in combination with a vancomycin- and
      gentamicin-eluting spacer system in the course of a two-stage revision procedure
      for deep infection with a median follow-up of 49 months (25 to 83). The
      antibiotic-eluting articulating spacers fractured in six hips (13.9%) and
      dislocated in five patients (11.6%). Successful elimination of the infecting
      organisms occurred in 38 (92.7%) of 41 hips with three patients developing
      superinfection with a new organism. We conclude that prolonged systemic
      antibiotic therapy may not be essential in the two-stage treatment of a total hip
      replacement for Gram-positive infection, provided that a high concentration of
      antibiotics is delivered locally using an antibiotic-eluting system.

PMID- 19092004
TI  - Unicompartmental or total knee replacement: the 15-year results of a prospective
      randomised controlled trial.
AB  - Between 1989 and 1992 we had 102 knees suitable for unicompartmental knee
      replacement (UKR). They were randomised to receive either a St Georg Sled UKR or
      a Kinematic modular total knee replacement (TKR). The early results demonstrated
      that the UKR group had less complications and more rapid rehabilitation than the
      TKR group. At five years there were an equal number of failures in the two groups
      but the UKR group had more excellent results and a greater range of movement. The
      cases were reviewed by a research nurse at 8, 10 and 12 years after operation. We
      report the outcome at 15 years follow-up. A total of 43 patients (45 knees) died
      with their prosthetic knees intact. Throughout the review period the Bristol knee
      scores of the UKR group have been better and at 15 years 15 (71.4%) of the
      surviving UKRs and 10 (52.6%) of the surviving TKRs had achieved an excellent
      score. The 15 years survivorship rate based on revision or failure for any reason
      was 24 (89.8%) for UKR and 19 (78.7%) for TKR. During the 15 years of the review
      four UKRs and six TKRs failed. The better early results with UKR are maintained
      at 15 years with no greater failure rate. The median Bristol knee score of the
      UKR group was 91.1 at five years and 92 at 15 years, suggesting little functional
      deterioration in either the prosthesis or the remainder of the joint. These
      results justify the increased use of UKR.

PMID- 19092005
TI  - The low contact stress mobile-bearing total knee replacement: a prospective study
      with a minimum follow-up of ten years.
AB  - We have examined the outcome of 400 consecutive patients who underwent total knee
      replacement with the Low Contact Stress mobile-bearing system between 1993 and
      1994 and were followed up for a minimum of ten years. All operations were
      performed by surgeons in Christchurch, New Zealand, who used no other knee
      prosthesis during the study time. At ten years after operation 238 patients (244
      knees) remained for independent clinical and radiological assessment. There was a
      significant improvement (p < 0.001) in the postoperative knee scores at one,
      three, seven and ten years, although a slight deterioration in the score occurred
      between seven and ten years which did not reach statistical significance. The
      survival for polyethylene wear or loosening was 97% (95% CI 96 to 98) and
      survival using reoperation for any cause was 92% (95% CI 90 to 94) at 12 years.
      Polyethylene wear was more common in the meniscal-bearing component, with five
      knees requiring revision and a further eight demonstrating early wear. Osteolysis
      was not seen in the rotating platform component, but was present in three of the
      meniscal-bearing knees. There was no association between the radiological
      alignment at one year and those knees that subsequently required revision.
      However, there was an association between the overall limb alignment and the
      Western Ontario McMasters University score (p < 0.001). The Low Contact Stress
      mobile-bearing total knee replacement has proved to be a reliable implant at ten
      years when used in primary knee replacement irrespective of the deformity and
      diagnosis.

PMID- 19092006
TI  - Simultaneous bilateral sequential total knee replacement is as safe as unilateral
      total knee replacement.
AB  - We wished to determine whether simultaneous bilateral sequential total knee
      replacement (TKR) carried increased rates of mortality and complications compared
      with unilateral TKR in low- and high-risk patients. Our study included 2385
      patients who had undergone bilateral sequential TKR under one anaesthetic and 719
      who had unilateral TKR. There were no significant pre-operative differences
      between the groups in terms of age, gender, height, weight, body mass index,
      diagnosis, comorbidity and duration of follow-up, which was a mean of 10.2 years
      (5 to 14) in the bilateral and 10.4 years (5 to 14) in the unilateral group. The
      peri-operative mortality rate (eight patients, 0.3%) of patients who had
      bilateral sequential TKR was similar to that (five patients, 0.7%) of those
      undergoing unilateral TKR. In bilateral cases the peri-operative mortality rate
      (three patients, 0.4%) of patients at high risk was similar to that (five
      patients, 0.3%) of patients at low risk as it was also in unilateral cases (two
      patients, 1.0% vs three patients, 0.6%). There was no significant difference (p =
      0.735) in either the overall number of major complications between bilateral and
      unilateral cases or between low- (p = 0.57) and high-risk (p = 0.61) patients.
      Also, the overall number of minor complications was not significantly different
      between the bilateral and unilateral group (p = 0.143). Simultaneous bilateral
      sequential TKR can be offered to patients at low and high risk and has an
      expected rate of complications similar to that of unilateral TKR.

PMID- 19092007
TI  - A randomised, controlled trial of two mobile-bearing total ankle replacements.
AB  - We describe the results of a randomised, prospective study of 200 ankle
      replacements carried out between March 2000 and July 2003 at a single centre to
      compare the Buechel-Pappas (BP) and the Scandinavian Total Ankle Replacement
      (STAR) implant with a minimum follow-up of 36 months. The two prostheses were
      similar in design consisting of three components with a meniscal polyethylene
      bearing which was highly congruent on its planar tibial surface and on its curved
      talar surface. However, the designs were markedly different with respect to the
      geometry of the articular surface of the talus and its overall shape. A total of
      16 ankles (18%) was revised, of which 12 were from the BP group and four of the
      STAR group. The six-year survivorship of the BP design was 79% (95% confidence
      interval (CI) 63.4 to 88.5 and of the STAR 95% (95% CI 87.2 to 98.1). The
      difference did not reach statistical significance (p = 0.09). However, varus or
      valgus deformity before surgery did have a significant effect) (p = 0.02) on
      survivorship in both groups, with the likelihood of revision being directly
      proportional to the size of the angular deformity. Our findings support previous
      studies which suggested that total ankle replacement should be undertaken with
      extreme caution in the presence of marked varus or valgus deformity.

PMID- 19092008
TI  - Revision of the humeral component for aseptic loosening in arthroplasty of the
      shoulder.
AB  - Between 1976 and 2004, 38 revision arthroplasties (35 patients) were performed
      for aseptic loosening of the humeral component. The mean interval from primary
      arthroplasty to revision was 7.1 years (0.4 to 16.6). A total of 35 shoulders (32
      patients) were available for review at a mean follow-up of seven years (2 to
      19.3). Pre-operatively, 34 patients (97%) had moderate or severe pain; at final
      follow-up, 29 (83%) had no or only mild pain (p < 0.0001). The mean active
      abduction improved from 88 degrees to 107 degrees (p < 0.01); and the mean
      external rotation from 37 degrees to 46 degrees (p = 0.27). Excellent or
      satisfactory results were achieved in 25 patients (71%) according to the modified
      Neer rating system. Humeral components were cemented in 29, with ingrowth
      implants used in nine cases. There were 19 of standard length and 17 were longer
      (two were custom replacements and are not included). Bone grafting was required
      for defects in 11 humeri. Only two glenoid components were left unrevised. Intra
      operative complications included cement extrusion in eight cases, fracture of the
      shaft of the humerus is two and of the tuberosity in four. There were four re
      operations, one for recurrent humeral loosening, with 89% survival free of re
      operations at ten years. Revision surgery for aseptic loosening of the humeral
      component provides reliable pain relief and modest improvement of movement,
      although there is a substantial risk of intra-operative complications. Revision
      to a total shoulder replacement gives better results than to a hemiarthroplasty.

PMID- 19092009
TI  - Posterolateral rotatory laxity following surgery to the head of the radius:
      biomechanical comparison of two surgical approaches.
AB  - The lateral ligament complex is the primary constraint to posterolateral rotatory
      laxity of the elbow, and if it is disrupted during surgery, posterolateral
      instability may ensue. The Wrightington approach to the head of the radius
      involves osteotomising the ulnar insertion of this ligament, rather than incising
      through it as in the classic posterolateral (Kocher) approach. In this
      biomechanical study of 17 human cadaver elbows, we demonstrate that the surgical
      approach to the head can influence posterolateral laxity, with the Wrightington
      approach producing less posterolateral rotatory laxity than the posterolateral
      approach.

PMID- 19092010
TI  - Brachial plexus-avulsion causing Brown-Sequard syndrome: a report of three cases.
AB  - We describe three patients with pre-ganglionic (avulsion) injuries of the
      brachial plexus which caused a partial Brown-Sequard syndrome.

PMID- 19092011
TI  - Fractures of the upper transthoracic cage.
AB  - We have reviewed our experience in managing 11 patients who sustained an indirect
      sternal fracture in combination with an upper thoracic spinal injury between 2003
      and 2006. These fractures have previously been described as 'associated'
      fractures, but since the upper thorax is an anatomical entity composed of the
      upper thoracic spine, ribs and sternum joined together, we feel that the term
      'fractures of the upper transthoracic cage' is a better description. These
      injuries are a challenge because they are unusual and easily overlooked. They
      require a systematic clinical and radiological examination to identify both
      lesions. This high-energy trauma gives severe devastating concomitant injuries
      and CT with contrast and reconstruction is essential after resuscitation to
      confirm the presence of all the lesions. The injury level occurs principally at
      T4-T5 and at the manubriosternal joint. These unstable fractures need early
      posterior stabilisation and fusion or, if treated conservatively, a very close
      follow-up.

PMID- 19092012
TI  - Outcome, following significant delays in initial surgery, of ballistic femoral
      fractures managed without internal or external fixation.
AB  - We reviewed the clinical details and radiographs of 52 patients with ballistic
      fractures of the femur admitted to the International Committee of the Red Cross
      Hospital in Kenya (Lopiding), who had sustained injuries in neighbouring Sudan.
      In all cases there had been a significant delay in the initial surgery (> 24
      hours), and all patients were managed without stabilisation of the fracture by
      internal or external fixation. Of the 52 patients, three required an amputation
      for persisting infection of the fracture site despite multiple debridements. A
      further patient was treated by an excision arthroplasty of the hip, but this was
      carried out at the initial operation as a part of the required debridement. All
      of the remaining 48 fractures healed. Four patients needed permanent shoe
      adaptation because of limb shortening of functional significance. Although we do
      not advocate delaying treatment or using traction instead of internal or external
      fixation, we have demonstrated that open femoral fractures can heal despite
      limited resources.

PMID- 19092013
TI  - The effect of an associated ulnar styloid fracture on the outcome after fixation
      of a fracture of the distal radius.
AB  - A total of 118 consecutive patients with a fracture of the distal radius were
      treated with a volar locking plate; 50 patients had no ulnar styloid fracture, 41
      had a basal ulnar styloid fracture, and 27 had a fracture of the tip of the ulnar
      styloid. There were no significant differences in radiological and clinical
      results among the three groups. The outcome was good and was independent of the
      presence of a fracture of the ulnar styloid. A total of five patients (4.2%) had
      persistent ulnar-sided wrist pain at final follow-up. Nonunion of the ulnar
      styloid fracture did not necessarily lead to ulnar wrist pain. Patients with
      persistent ulnar pain had a higher mean initial ulnar variance and increased post
      operative loss of ulnar variance. The presence of an associated ulnar styloid
      fracture of the ulnar styloid does not adversely affect the outcome in patients
      with a fracture of the distal radius treated by volar plating.

PMID- 19092014
TI  - Modular endoprosthetic replacement for tumours of the proximal femur.
AB  - Endoprosthetic replacement of the proximal femur may be required to treat primary
      bone tumours or destructive metastases either with impending or established
      pathological fracture. Modular prostheses are available off the shelf and can be
      adapted to most reconstructive situations for this purpose. We have assessed the
      clinical and functional outcome of using the METS (Stanmore Implants Worldwide)
      modular tumour prosthesis to reconstruct the proximal femur in 100 consecutive
      patients between 2001 and 2006. We compared the results with the published series
      for patients managed with modular and custom-made endoprosthetic replacements for
      the same conditions. There were 52 males and 48 females with a mean age of 56.3
      years (16 to 84) and a mean follow-up of 24.6 months (0 to 60). In 65 patients
      the procedure was undertaken for metastases, in 25 for a primary bone tumour, and
      in ten for other malignant conditions. A total of 46 patients presented with a
      pathological fracture, and 19 presented with failed fixation of a previous
      pathological fracture. The overall patient survival was 63.6% at one year and
      23.1% at five years, and was significantly better for patients with a primary
      bone tumour than for those with metastatic tumour (82.3% vs 53.3%, respectively
      at one year (p = 0.003)). There were six early dislocations of which five could
      be treated by closed reduction. No patient needed revision surgery for
      dislocation. Revision surgery was required by six (6%) patients, five for pain
      caused by acetabular wear and one for tumour progression. Amputation was needed
      in four patients for local recurrence or infection. The estimated five-year
      implant survival with revision as the endpoint was 90.7%. The mean Toronto
      Extremity Salvage score was 61% (51% to 95%). The implant survival and
      complications resulting from the use of the modular system were comparable to the
      published series of both custom-made and other modular proximal femoral implants.
      We conclude that at intermediate follow-up the modular tumour prosthesis for
      proximal femur replacement provides versatility, a low incidence of implant
      related complications and acceptable function for patients with metastatic
      tumours, pathological fractures and failed fixation of the proximal femur. It
      also functions as well as a custom-made endoprosthetic replacement.

PMID- 19092015
TI  - One-stage bilateral open reduction through a medial approach in developmental
      dysplasia of the hip.
AB  - The outcome of one-stage bilateral open reduction through a medial approach for
      the treatment of developmental dysplasia of the hip in children under 18 months
      was studied in 23 children, 18 girls and five boys. Their mean age at operation
      was 10.1 months (6 to 17) and the mean follow-up was 5.4 years (3 to 8).
      Acceptable clinical and radiological results were achieved in 44 (95.7%) and 43
      (93.5%) of 46 hips, respectively. Excellent results were significantly evident in
      patients younger than 12 months, those who did not require acetabuloplasty, those
      whose ossific nucleus had appeared, and in those who did not develop avascular
      necrosis. One-stage bilateral medial open reduction avoids the need for separate
      procedures on the hips and has the advantages of accelerated management and
      shorter immobilisation and rehabilitation than staged operations.

PMID- 19092016
TI  - The morphological and immunocytochemical features of impingement syndrome and
      partial-thickness rotator-cuff tear in relation to outcome after subacromial
      decompression.
AB  - We assessed the predictive value of the macroscopic and detailed microscopic
      appearance of the coracoacromial ligament, subacromial bursa and rotator-cuff
      tendon in 20 patients undergoing subacromial decompression for impingement in the
      absence of full-thickness tears of the rotator cuff. Histologically, all
      specimens had features of degenerative change and oedema in the extracellular
      matrix. Inflammatory cells were seen, but there was no evidence of chronic
      inflammation. However, the outcome was not related to cell counts. At three
      months the mean Oxford shoulder score had improved from 29.2 (20 to 40) to 39.4
      (28 to 48) (p < 0.0001) and at six months to 45.5 (36 to 48) (p < 0.0001). At six
      months, although all patients had improved, the seven patients with a hooked
      acromion had done so to a less extent than those with a flat or curved acromion
      judged by their mean Oxford shoulder scores of 43.5 and 46.5 respectively (p =
      0.046). All five patients with partial-thickness tears were within this group and
      demonstrated less improvement than the patients with no tear (mean Oxford
      shoulder scores 43.2 and 46.4, respectively, p = 0.04). These findings imply that
      in the presence of a partial-thickness tear subacromial decompression may require
      additional specific treatment to the rotator cuff if the outcome is to be
      improved further.

PMID- 19092017
TI  - Alterations in femoral strain following hip resurfacing and total hip
      replacement.
AB  - Bone surface strains were measured in cadaver femora during loading prior to and
      after resurfacing of the hip and total hip replacement using an uncemented,
      tapered femoral component. In vitro loading simulated the single-leg stance phase
      during walking. Strains were measured on the medial and the lateral sides of the
      proximal aspect and the mid-diaphysis of the femur. Bone surface strains
      following femoral resurfacing were similar to those in the native femur, except
      for proximal shear strains, which were significantly less than those in the
      native femur. Proximomedial strains following total hip replacement were
      significantly less than those in the native and the resurfaced femur. These
      results are consistent with previous clinical evidence of bone loss after total
      hip replacement, and provide support for claims of bone preservation after
      resurfacing arthroplasty of the hip.

PMID- 19092018
TI  - Assessment of vascularity of the femoral head using gadolinium (Gd-DTPA)-enhanced
      magnetic resonance imaging: a cadaver study.
AB  - In spite of extensive accounts describing the blood supply to the femoral head,
      the prediction of avascular necrosis is elusive. Current opinion emphasises the
      contributions of the superior retinacular artery but may not explain the clinical
      outcome in many situations, including intramedullary nailing of the femur and
      resurfacing of the hip. We considered that significant additional contribution to
      the vascularity of the femoral head may exist. A total of 14 fresh-frozen hips
      were dissected and the medial circumflex femoral artery was cannulated in the
      femoral triangle. On the test side, this vessel was ligated, with the femoral
      head receiving its blood supply from the inferior vincular artery alone.
      Gadolinium contrast-enhanced MRI was then performed simultaneously on both
      control and test specimens. Polyurethane was injected, and gross dissection of
      the specimens was performed to confirm the extraosseous anatomy and the injection
      of contrast. The inferior vincular artery was found in every specimen and had a
      significant contribution to the vascularity of the femoral head. The head was
      divided into four quadrants: medial (0), superior (1), lateral (2) and inferior
      (3). In our study specimens the inferior vincular artery contributed a mean of
      56% (25% to 90%) of blood flow in quadrant 0, 34% (14% to 80%) of quadrant 1, 37%
      (18% to 48%) of quadrant 2 and 68% (20% to 98%) in quadrant 3. Extensive intra
      osseous anastomoses existed between the superior retinacular arteries, the
      inferior vincular artery and the subfoveal plexus.

PMID- 19092019
TI  - What is the point of the American-British-Canadian (ABC) fellowship?

PMID- 19092020
TI  - Change, we have to.

PMID- 19092021
TI  - HIV: know your epidemic, act on its politics.

PMID- 19092022
TI  - Sudden whitening of the hair: an historical fiction?

PMID- 19092023
TI  - EBM and CAM.

PMID- 19092024
TI  - Changing life expectancy throughout history.

PMID- 19092026
TI  - Is psychiatry a religion?

PMID- 19092027
TI  - Jacques-Louis David's tumour: an opportunity to study the natural history of a
      pleomorphic adenoma of the parotid gland.
AB  - The great artist and one-time revolutionary, Jacques-Louis David died in 1825.
      The cause of his death has been open to speculation. An extraordinary sequence of
      portraits of the artist describes his transition from handsome middle age to a
      deformed old man. During this phase a swelling appears at the angle of his left
      jaw and over a period of 20 years a facial palsy can be diagnosed. We submit that
      this evidence suggests that malignant transformation of a pleomorphic adenoma of
      the parotid gland was the proximal cause of his death.

PMID- 19092028
TI  - Sneezing induced by sexual ideation or orgasm: an under-reported phenomenon.
AB  - We describe a hitherto under-recognized curious response in some individuals: of
      sneezing in response either to sexual ideation or in response to orgasm. Our
      review suggests that it may be much more common than expected. We surmise that an
      indiscrete stimulation of the parasympathetic nervous system may be an underlying
      mechanism to explain this and other reported unusual triggers of sneezing.

PMID- 19092029
TI  - The views of doctors on their working lives: a qualitative study.
AB  - OBJECTIVE: To describe doctors' views on, and responses to, their professional
      working lives in the UK National Health Service (NHS). DESIGN: Qualitative study
      using semi structured interviews. Setting Two district hospitals and primary care
      settings in the North of England. PARTICIPANTS: Fifty-two doctors participated in
      the study--47 worked in hospital and five worked in general practice. MAIN
      OUTCOME MEASURES: Qualitative information regarding doctors' views on their
      working lives. RESULTS: The study provided insights into the views of their
      working lives of a sample of doctors in the NHS. Feelings they articulated
      contained a number of ambivalences. Feelings about the future were coloured by
      concerns about the impact of regulatory changes and processes of modernization on
      the experiential knowledge of doctors. CONCLUSIONS: These insights into doctors'
      views of their working lives might usefully inform those involved in the planning
      and overseeing of changes to health service structures and systems.

PMID- 19092030
TI  - Can clinicians benefit from patient satisfaction surveys? Evaluating the NSF for
      Older People, 2005-2006.
AB  - BACKGROUND: A transformation of healthcare is underway, from a sellers' market to
      a consumers' market, where the satisfaction of the patient's needs is part of the
      definition of quality. Patient satisfaction surveys are widely used to judge
      service quality, but clinicians are sceptical about them because they are too
      often poorly designed measures that do not lead to improvements in the quality of
      care. AIM: To explore the use of patient satisfaction survey data in identifying
      problems with the provision of inpatient care for older people. METHODS: A case
      study using secondary analysis of postal survey data about older people's
      experiences of health and social care services, obtained during the evaluation of
      the National Service Framework for Older People in 2005-2006. The survey asked
      about experiences of inpatient care and of discharge from hospital, and sought
      perceptions of the avoidability of the admission. SETTINGS AND PARTICIPANTS: A
      total of 4170 people aged 50 years and over returned a postal questionnaire in
      six local authority areas of England. Responses from 584 who had experienced a
      recent overnight stay in hospital are reported and discussed. FINDINGS: The
      response rate was 35%, ranging from 26% to 44% in the six areas surveyed. The
      great majority of those who had recent direct experience of inpatient care
      reported that they had been engaged in decision-making, that staff promoted their
      independence and maintained their dignity. There were widespread examples,
      however, of the opposite experiences. Discharge from hospital was problematic for
      about one-third of survey respondents with this experience, and there were
      different accounts of poorly managed discharges from all areas. CONCLUSIONS: Case
      studies using local survey data can be used as formative assessments of services.
      The response rate to the survey and the likelihood of responder bias mean that
      patient satisfaction survey data of this sort cannot be used to judge or compare
      services in a summative way, but can highlight areas where remedial action is
      needed. Small-scale local surveys may seem to lack the robustness of larger
      studies, but do identify similar areas of concern. Commissioners and clinicians
      could use the findings of such surveys to inform dialogues about the quality of
      hospital care for older people.

PMID- 19092031
TI  - Edward Alanson, 1782: responsibility in surgical innovation.

PMID- 19092032
TI  - Time will tell.

PMID- 19092034
TI  - Is positive well-being protective of mobility limitations among older adults?
AB  - This study examined associations among life satisfaction, perceptions of future
      happiness, and mobility limitations in a population-based sample of 3,363 older
      persons from the Survey of Health and Living Status of the Near Elderly and
      Elderly in Taiwan. We used zero-inflated Poisson regression to determine if
      current life satisfaction and perceptions of future happiness were independently
      related to the number of mobility limitations that developed during an
      approximately 8-year period. We adjusted for sociodemographic characteristics,
      health status, social involvement, and depressive symptoms at baseline. Life
      satisfaction and perceptions of future happiness were both associated with the
      development of fewer mobility limitations during follow-up, but only for those
      participants who had no mobility limitations at baseline. The results suggest a
      protective relationship between psychological well-being and physical decline in
      later life.

PMID- 19092035
TI  - How are personality traits related to preparation for future care needs in older
      adults?
AB  - We investigated associations between personality and health cognitions and
      behaviors related to preparation for future care among 355 primary care patients
      who were 65 years of age and older. Path analyses examined the effects of the
      personality traits of neuroticism, extraversion, openness to experience,
      agreeableness, and conscientiousness on health cognitions about future care
      (avoidance, awareness), health-planning behaviors (gathering information,
      decision making, and planning), and beliefs about planning, while covarying age,
      gender, education, medical burden, functional status, and depression-symptom
      severity. Higher levels of neuroticism, openness, and agreeableness were
      associated with greater awareness of care needs; higher openness was also
      associated with more gathering of information and less avoidance. Extraversion
      and conscientiousness were not related to future-oriented health cognitions.
      Depression was inversely associated with the gathering of information. Age and
      education were related to more positive beliefs about the planning. Neither
      concrete planning nor decision making were related to personality variables.
      Health professionals should consider the impact of individual differences when
      addressing preparation for future care with older adults.

PMID- 19092036
TI  - Interpretation of emotionally ambiguous faces in older adults.
AB  - Research suggests that there is an age-related decline in the processing of
      negative emotional information, which may contribute to the reported decline in
      emotional problems in older people. We used a signal detection approach to
      investigate the effect of normal aging on the interpretation of ambiguous
      emotional facial expressions. High-functioning older and younger adults indicated
      which emotion they perceived when presented with morphed faces containing a 60%
      to 40% blend of two emotions (mixtures of happy, sad, or angry faces). They also
      completed measures of mood, perceptual ability, and cognitive functioning. Older
      and younger adults did not differ significantly in their ability to discriminate
      between positive and negative emotions. Response-bias measures indicated that
      older adults were significantly less likely than younger adults to report the
      presence of anger in angry-happy face blends. Results are discussed in relation
      to other research into age-related effects on emotion processing.

PMID- 19092037
TI  - Age-related loss of adaptability to fast time scales in motor variability.
AB  - We investigated the ability of older adults to intentionally adapt their
      sensorimotor output to differing time and frequency properties (1/f noise
      structure) of a target-force target waveform. We tested the hypothesis that
      elderly adults are less adaptable than their younger counterparts to the time-
      and frequency-dependent demands of continuous sensorimotor output and that this
      effect is mediated by the frequency content of the task demand. The results
      showed that older adults were progressively less able than young adults to
      approximate the lighter-color-noise force targets and utilize the information in
      the higher frequencies of the target signal. There is a declining ability with
      aging to use the faster time scales of sensorimotor control, but the particular
      directional effect of the loss or gain of complexity of force output is moderated
      by the differential impact of task demands.

PMID- 19092038
TI  - The mediating role of perceived control on the relationship between socioeconomic
      status and functional changes in older patients with coronary heart disease.
AB  - Using a prospective design, this study examines the mediating effect of perceived
      control in explaining the predictive role of socioeconomic status (SES) in long
      term changes in functional status as a consequence of the occurrence of coronary
      heart disease (CHD). We followed 221 older CHD patients by using a community
      based survey. We collected data on patients' functional status before the onset
      of disease and 1 year after the diagnosis. Multiple linear regressions show that
      SES predicts functional changes only in relation to physical functioning.
      Furthermore, self-efficacy, but not mastery, mediates the predictive role of SES
      in changes in physical functioning in CHD patients. Self-efficacy is the only
      aspect of control that mediates the relation between SES and changes in physical
      functioning. Our findings provide a basis for future interventions in
      disadvantaged groups of older persons and new theoretical models of recovery
      processes.

PMID- 19092040
TI  - Caregiving for Parkinson's disease patients: an exploration of a stress-appraisal
      model for quality of life and burden.
AB  - Extending the 2002 stress-appraisal model of Chappell and Reid, we examined the
      relationships between caregiver stressors (e.g., cognitive impairment and
      functional dependency of the recipient), appraisal (informal hours of
      caregiving), and protective factors (e.g., social support, self-esteem, and
      quality of the caregiver-recipient relationship) associated with the burden and
      quality of life of Parkinson's disease caregivers. There were 136 caregivers (M =
      64.59 years) who completed an online survey. Using structural equation modeling,
      we found that the extended stress-appraisal model of Chappell and Reid provided a
      good fit to the data (chi2 = 67.87, df = 55, p >.05; chi2/df = 1.23, Comparative
      Fit Index = 0.98, Root Mean Square Error of Approximation = 0.04). This study
      provides an important contribution to a growing field of research that applies
      theoretical models to investigate the stressors, appraisals, and protective
      factors that impact caregiver well-being.

PMID- 19092039
TI  - Ambivalent relationship qualities between adults and their parents: implications
      for the well-being of both parties.
AB  - This study considered whether intergenerational ambivalence has implications for
      each party's psychological well-being and physical health. Participants included
      158 families (N = 474) with a mother, a father, and a son or daughter aged 22 to
      49 years. Actor-partner interaction models revealed that parents and offspring
      who self-reported greater ambivalence showed poorer psychological well-being.
      Partner reports of ambivalence were associated with poorer physical health. When
      fathers reported greater ambivalence, offspring reported poorer physical health.
      When grown children reported greater ambivalence, mothers reported poorer
      physical health. Fathers and offspring who scored lower in neuroticism showed
      stronger associations between ambivalence and well-being. Findings suggest that
      parents or offspring may experience greater ambivalence when the other party is
      in poorer health and that personality moderates associations between relationship
      qualities and well-being.

PMID- 19092041
TI  - Self-perceptions of aging: do subjective age and satisfaction with aging change
      during old age?
AB  - The present study examined time-related change in felt age, physical age, and
      satisfaction with aging in old age and covariates of this change. Using 6-year
      longitudinal data from the Berlin Aging Study (age range = 70-104 years), we
      found that individuals' felt age remained on average about 13 years below their
      actual age over time, whereas they reported a decreasing discrepancy between
      physical and actual age and a decrease in aging satisfaction over time. After we
      controlled for level differences, a differential pattern of individual
      differences in change appeared for the three dimensions: Age contributed to a
      greater decline in aging satisfaction but an increase in the discrepancy of felt
      age. A higher number of illnesses at baseline attenuated change in felt age
      discrepancy. Future research on change of self-perceptions of aging will provide
      insight into mechanisms of resilience of the aging self in later life.

PMID- 19092042
TI  - Exploring the within-person coupling of blood pressure and cognition in elders.
AB  - In this study, we examined the relationship between within-person blood pressure
      and cognitive functioning. We conducted an analysis on 36 community-dwelling
      elderly individuals (age range = 60-87 years). Participants measured their blood
      pressure and completed cognitive tasks (i.e., the Rey Auditory Verbal Learning
      Task, the Letter Series test, and the Number Comparison test) twice a day over 60
      consecutive days. We observed a significant interaction between within-person
      change in blood pressure and average blood pressure for the Letter Series test.
      Individuals with high blood pressure tended to perform poorly, particularly on
      occasions when their blood pressure level was above their personal average. These
      results demonstrate that the relationship between blood pressure and cognition at
      the between-person level and the relationship within each individual should be
      further explored simultaneously.

PMID- 19092043
TI  - Early life exposure to poor nutrition and infectious diseases and its effects on
      the health of older Puerto Rican adults.
AB  - OBJECTIVES: We examined the effects of early life exposure to poor nutrition and
      infectious diseases on adult heart disease and diabetes using season of birth as
      an indicator to help disentangle the effects on health of early life exposure
      from effects associated with other childhood conditions. METHODS: Using data from
      60- to 74-year-old Puerto Ricans who lived in rural areas during childhood (n =
      1,457), we estimated the effects of seasonal exposure during late gestation on
      the probability of diabetes and heart disease, controlling for adult obesity and
      other childhood conditions (health, socioeconomic status, knee height). RESULTS:
      We found (a) strong associations between exposure and heart disease; (b) weaker
      associations between exposure and diabetes, although significant negative
      interaction effects between exposure and having a family member with diabetes
      suggest the possibility of either strong gene-environment or early adult
      environment interactions; (c) virtually no attenuation of effects of self
      reported childhood health with controls for exposure. DISCUSSION: Timing of birth
      may reveal conditions experienced perinatally that affect adult heart disease and
      diabetes. The results suggest that examination of the effects of season of birth
      on these chronic conditions among older Puerto Rican adults and among older
      adults from similar populations deserves deeper scrutiny.

PMID- 19092044
TI  - Parental marital disruption, family type, and transfers to disabled elderly
      parents.
AB  - OBJECTIVE: The objective of this study was to investigate the effect of parental
      marital status, marital history, and family type on intergenerational living
      arrangements and adult children's time and cash transfers to their unpartnered
      disabled elderly parents. METHODS: We used data from the Asset and Health
      Dynamics Among the Oldest Old survey to estimate the joint probabilities that an
      adult child provides time and/or cash transfers to a parent and to analyze a five
      level categorical variable capturing parent-child living arrangements. RESULT:
      The estimates suggest significant detrimental effects of parental divorce and
      step relationship on time transfers and on the probability of coresidence with
      the index child. Family type, as captured by the composition of the index child's
      sibling network according to kin relationship to the parent, also affected
      transfers and living arrangement choices of adult children. DISCUSSION: The
      findings that transfers from adult children to their unpartnered disabled elderly
      parents depend on parental marital status and kin relationship suggest that
      changing family patterns are altering the traditional role of the family as a
      support network. These findings raise concerns about the care likely to be
      available to future cohorts of elderly persons who will have experienced
      substantially higher rates of divorce, remarriage, and step parenthood than the
      cohort considered in this study.

PMID- 19092045
TI  - Differences over time in the relationship between partnership disruptions and
      support in early old age in Britain.
AB  - OBJECTIVE: We examined variations over time in the relationship between past
      partnership disruption (due to divorce, separation, and death) and present
      support (coresidence with, help to and from, and contact with children) in early
      old age in Britain. METHODS: Employing data from the 2001/2 British Household
      Panel Survey and the 1988/9 Survey of Retirement and Retirement Plans, we
      investigated whether differences in support over time were due to changes in (a)
      the composition of the population (e.g., the percentage divorced) or (b) the
      strength of the covariates (e.g., the effect of divorce). RESULT: Our findings
      showed an increase in the experience of partnership disruption in early old age.
      Nonetheless, the percentage of people who reported receiving and providing
      support increased. A comparison of the two points in time showed that there was
      little change in the effects of partnership disruptions on support in early old
      age. DISCUSSION: The fact that the level of support has remained stable or
      increased over time among this age group despite the increasing prevalence of
      divorce suggests that the negative effect of partnership disruption on support in
      early old age may be weakening over time.

PMID- 19092046
TI  - Effect of financial strain on mortality in community-dwelling older women.
AB  - OBJECTIVES: Although it is well established that low socioeconomic status is
      related to mortality, little research has focused on whether financial strain
      predicts mortality. Still less research has examined this question by race,
      despite the evidence that African Americans suffer earlier mortality and more
      financial strain at the same levels of socioeconomic status than their Caucasian
      counterparts. We examined the extent to which financial strain was associated
      with increased mortality risk in older women and whether the relationship
      differed by race. METHODS: The sample was the Women's Health and Aging Studies I
      and II of community-dwelling older women aged 70 to 79. We used Cox proportional
      hazards models to estimate the effect of financial strain on 5-year mortality
      rates. RESULTS: Women who reported financial strain were almost 60% more likely
      to die within 5 years independent of race, age, education, absolute income,
      health insurance status, and comorbidities (p <.001) than their counterparts who
      did not. Although race was not a predictor of mortality, the association between
      financial strain and mortality was stronger for African Americans than for
      Caucasians (p <.01). DISCUSSION: For older women, financial strain may be a
      better predictor of mortality than annual income, particularly in the case of
      older African American women.

PMID- 19092048
TI  - Using freelisting to identify, assess, and characterize age differences in shared
      cultural domains.
AB  - OBJECTIVE: Freelisting is a brief, paper-and-pencil technique in which
      participants make lists of items that they believe belong in a particular domain.
      Where cultural domains are shared, as for young and old in the same society,
      subtle intracultural differences may be difficult to detect. This article
      presents a series of techniques for revealing and describing this intracultural
      variation in freelisted data among young versus old age groups. METHODS: Older (N
      = 30) and younger (N = 31) Mexicans in Mexico City made freelists in four
      quotidian domains: animals, emotions, illnesses, and gendered occupations.
      RESULT: We used minimum residual factor analysis (consensus analysis) to
      establish domain coherence and assess overall consensus concerning contents of
      the domains. We established subvariation within the overall consensus by
      comparing levels of observed versus predicted inter-informant agreement. Results
      showed divergent patterns of inter-informant agreement between young and old
      participants across domains. Qualitative examination of items with higher
      salience for young versus old revealed age differences consistent with prior
      findings in each domain. DISCUSSION: The concatenation of these techniques
      renders freelisting an accessible, easily administered tool for probing age and
      group differences in cultural domains.

PMID- 19092047
TI  - From social structural factors to perceptions of relationship quality and
      loneliness: the Chicago health, aging, and social relations study.
AB  - OBJECTIVE: The objective of this study was to test a conceptual model of
      loneliness in which social structural factors are posited to operate through
      proximal factors to influence perceptions of relationship quality and loneliness.
      METHODS: We used a population-based sample of 225 White, Black, and Hispanic men
      and women aged 50 through 68 from the Chicago Health, Aging, and Social Relations
      Study to examine the extent to which associations between sociodemographic
      factors and loneliness were explained by socioeconomic status, physical health,
      social roles, stress exposure, and, ultimately, by network size and subjective
      relationship quality. RESULT: Education and income were negatively associated
      with loneliness and explained racial/ethnic differences in loneliness. Being
      married largely explained the association between income and loneliness, with
      positive marital relationships offering the greatest degree of protection against
      loneliness. Independent risk factors for loneliness included male gender,
      physical health symptoms, chronic work and/or social stress, small social
      network, lack of a spousal confidant, and poor-quality social relationships.
      DISCUSSION: Longitudinal research is needed to evaluate the causal role of social
      structural and proximal factors in explaining changes in loneliness.

PMID- 19092049
TI  - Collective ambivalence: considering new approaches to the complexity of
      intergenerational relations.

PMID- 19092052
TI  - Uterosacral ligament smooth muscle cell apoptosis is increased in women with
      uterine prolapse.
AB  - PURPOSE: The purpose of this study was to compare the smooth muscle content and
      apoptosis of the uterosacral ligament in women with and without uterine prolapse.
      STUDY DESIGN: Uterosacral ligaments were sampled in women with (n = 9) or without
      (n = 9) uterine prolapse undergoing hysterectomy. Smooth muscle of the
      uterosacral ligament was identified by immunohistochemistry. Digital image
      analysis was used to determine the fractional area of smooth muscle in the
      histologic cross sections. Apoptosis was assessed by terminal deoxynucelotidyl
      transferase-mediated dUTP nick-end-labeling method. RESULTS: The fractional area
      of nonvascular smooth muscle in the uterosacral ligament of women with uterine
      prolapse was significantly decreased compared to women without prolapse (0.32 +/-
      0.12 vs. 0.42 +/- 0.03, P = .02) and the apoptotic index was significantly higher
      compared to women without prolapse (0.20 +/- 0.06 vs. 0.08 +/- 0.04, P < .01).
      CONCLUSION: The fraction of smooth muscle in the uterosacral ligaments is
      significantly decreased, and the rate of apoptosis is higher in women with
      uterine prolapse compared to women without prolapse.

PMID- 19092051
TI  - Reciprocal regulation of the platelet-derived growth factor receptor-beta and G
      protein-coupled receptor kinase 5 by cross-phosphorylation: effects on catalysis.
AB  - Signaling by the platelet-derived growth factor receptor-beta (PDGFRbeta) is
      diminished when the PDGFRbeta is phosphorylated on seryl residues by G protein
      coupled receptor kinase-5 (GRK5), but mechanisms for GRK5 activation by the
      PDGFRbeta remain obscure. We therefore tested whether the PDGFRbeta is able to
      tyrosine-phosphorylate and thereby activate GRK5. Purified GRK5 was tyrosine
      phosphorylated by the wild-type PDGFRbeta to a stoichiometry of 0.8 mol
      phosphate/mol GRK5, an extent approximately 5 times greater than observed with a
      Y857F PDGFRbeta mutant that fails to phosphorylate exogenous substrates but
      autophosphorylates and activates Src normally. The degree of PDGFRbeta-mediated
      phosphorylation of GRK5 correlated with GRK5 activity, as assessed by seryl
      phosphorylation of the PDGFRbeta in purified protein preparations, in intact
      cells expressing a tyrosine-to-phenylalanine GRK5 mutant, and in GRK5 peptide
      phosphorylation assays. However, tyrosyl phosphorylation of GRK5 was not
      necessary for GRK5-mediated phosphorylation of the beta(2)-adrenergic receptor,
      even though beta(2)-adrenergic receptor activation promoted tyrosyl
      phosphorylation of GRK5 in smooth muscle cells. Phosphorylation of the PDGFRbeta
      by GRK5 in smooth muscle cells or in purified protein preparations reduced
      PDGFRbeta-mediated peptide phosphorylation. In contrast, phosphorylation of GRK5
      by the PDGFRbeta enhanced the V(max) of GRK5-mediated peptide phosphorylation, by
      3.4-fold, without altering the GRK5 K(M) for peptide. We conclude that GRK5
      tyrosyl phosphorylation is required for the activation of GRK5 by the PDGFRbeta,
      but not by the beta(2)-adrenergic receptor, and that by activating GRK5, the
      PDGFRbeta triggers its own desensitization.

PMID- 19092053
TI  - Biomechanical evaluation of anterior cruciate ligament femoral fixation
      techniques.
AB  - BACKGROUND: A number of different femoral anterior cruciate ligament fixation
      techniques are currently in use. Slippage of the graft caused by excessive early
      loading or aggressive rehabilitation may negate benefits of surgery and result in
      a knee with undesirable laxity. HYPOTHESIS: Anterior cruciate ligament femoral
      graft slippage varies by fixation technique and amount of cyclic loading. STUDY
      DESIGN: Controlled laboratory study. METHODS: Graft slippage in 5 different soft
      tissue anterior cruciate ligament femoral fixation techniques (Bio-TransFix cross
      pin technique, Stratis ST cross-pin technique, Bilok ST transverse femoral screw,
      Delta tapered bio-interference screw, and single-loop TensionLok) was compared by
      cyclic loading of double-bundle grafts in porcine femurs. Graft slippage was
      measured using a differential variable reluctance transducer. RESULTS: The Bio
      TransFix had significantly less (P = .002) total graft slippage (1.14 +/- 0.43
      mm) compared to the Delta (3.74 +/- 3.25 mm), Bilok ST (3.92 +/- 2.28 mm), and
      TensionLok (5.09 +/- 1.12 mm) but not the Stratis ST (1.92 +/- 1.55 mm). All
      techniques showed the greatest amount of dynamic excursion (P < .001), slippage
      (P < .001), and percentage of total slippage (mean 68%, P < .001) during the
      first 100 cycles of loading. The TensionLok had the greatest amount of dynamic
      excursion during the first 100 cycles (4.15 +/- 1.00 mm) followed by the Bilok ST
      (3.37 +/- 2.07 mm), Delta (1.76 +/- 0.93 mm), and Stratis ST (1.75 +/- 0.96 mm);
      the Bio-TransFix demonstrated the least (1.26 +/- 0.48 mm). There was no
      statistical difference in failure load between repair techniques (P = .103).
      CONCLUSION: Graft slippage was statistically different between anterior cruciate
      ligament femoral fixation techniques for static and dynamic loading. All
      techniques exhibited the greatest amount of slippage during the first 100 cycles
      of loading. The differential variable reluctance transducer permitted evaluation
      of dynamic graft-construct-bone displacement during experimental loading,
      simulating the loading experienced during early rehabilitation. CLINICAL
      RELEVANCE: The optimal method of graft fixation for anterior cruciate ligament
      reconstruction remains unknown. In the current study, cross-pin constructs
      appeared to be superior to certain other available fixation systems.

PMID- 19092054
TI  - MHC class II transport at a glance.

PMID- 19092055
TI  - SNX9 - a prelude to vesicle release.
AB  - The sorting nexin SNX9 has, in the past few years, been singled out as an
      important protein that participates in fundamental cellular activities. SNX9
      binds strongly to dynamin and is partly responsible for the recruitment of this
      GTPase to sites of endocytosis. SNX9 also has a high capacity for modulation of
      the membrane and might therefore participate in the formation of the narrow neck
      of endocytic vesicles before scission occurs. Once assembled on the membrane,
      SNX9 stimulates the GTPase activity of dynamin to facilitate the scission
      reaction. It has also become clear that SNX9 has the ability to activate the
      actin regulator N-WASP in a membrane-dependent manner to coordinate actin
      polymerization with vesicle release. In this Commentary, we summarize several
      aspects of SNX9 structure and function in the context of membrane remodeling,
      discuss its interplay with various interaction partners and present a model of
      how SNX9 might work in endocytosis.

PMID- 19092057
TI  - Protein p0071 - an armadillo plaque protein that characterizes a specific subtype
      of adherens junctions.

PMID- 19092058
TI  - AAPL Practice Guideline for the Forensic Evaluation of Psychiatric Disability.

PMID- 19092056
TI  - microRNAs and muscle disorders.
AB  - MicroRNAs (miRNAs) are a class of non-coding regulatory RNAs of approximately 22
      nucleotides in length. miRNAs are highly conserved across a number of species,
      including plants, worms and humans. miRNAs regulate gene expression post
      transcriptionally, primarily by associating with the 3' untranslated region (UTR)
      of their regulatory target mRNAs. Recent work has begun to reveal roles for
      miRNAs in a wide range of biological processes, including cell proliferation,
      differentiation and apoptosis. miRNAs are expressed in cardiac and skeletal
      muscle, and dysregulated miRNA expression has been correlated with muscle-related
      disorders. Genetic studies have identified distinct roles for specific miRNAs
      during cardiogenesis, cardiac hypertrophy and electrical conduction. Furthermore,
      conditionally inhibiting the maturation of miRNAs in mouse cardiac and skeletal
      muscles has revealed that miRNAs are essential for the development and function
      of those muscles. These previously unrecognized regulators shed new light on the
      molecular mechanisms that underlie muscle development and pathology, and suggest
      the potential importance of miRNAs as diagnostic markers and therapeutic targets
      for muscle-related disease.

PMID- 19092059
TI  - The majority of inpatient psychiatric beds should not be appropriated by the
      forensic system.

PMID- 19092060
TI  - Use of DSM paraphilia diagnoses in sexually violent predator commitment cases.
AB  - There is legitimate concern in the psychiatric community about the
      constitutionality of sexually violent predator (SVP) commitment statutes. Such
      constitutionality depends on the requirement that a sexual offender have a mental
      abnormality that makes him commit violent predatory sex offenses and reflects
      almost exclusively a concern for public safety, with little regard for notions of
      clinical sensibility or diagnostic accuracy. However, given that mental health
      experts' diagnostic opinions are, and will continue to be, important to the
      triers of fact in regard to the application of the SVP statutes, we describe
      valid means of making a DSM-IV-TR paraphilic diagnosis. We also provide a three
      step approach for the judicious application of the diagnosis in the context of
      SVP commitment evaluations that emphasizes the importance of not making a
      paraphilia diagnosis based solely on the sexual offenses themselves. Finally, we
      discuss the appropriate use of a paraphilia NOS diagnosis in SVP cases.

PMID- 19092061
TI  - Commentary: muddy diagnostic waters in the SVP courtroom.
AB  - In this brief commentary, we address several of the points raised by Drs. First
      and Halon on the abuses of DSM diagnoses (APA, 2000) in civil commitment hearings
      of sex offenders. We discuss each of the elements in the three-step process
      proposed by First and Halon for reforming the diagnosis of paraphilias in SVP
      proceedings, paying particular attention to the role of volitional impairment.
      Both in spirit and in substance, we fundamentally agree with First and Halon,
      concluding that the misuse of science, inclusive of the misuse of the DSM, in the
      SVP courtroom is a variation of pretextuality. We commend First and Halon for
      drawing attention to a serious problem, one that undermines the integrity of the
      legal system in general and the SVP adjudicatory process in particular. We
      conclude with a warning that without firmer control from the courts, expert
      opinions will remain opaque and of questionable probative value.

PMID- 19092062
TI  - Commentary: inventing diagnosis for civil commitment of rapists.
AB  - In the past two decades, public fear and antipathy toward sexual offenders have
      led to public registries of their names and addresses, longer prison sentences,
      consideration of the death penalty, and civil commitment laws that allow
      potentially lifetime preventive detention after these offenders complete prison
      sentences. Twenty states and the federal government have enacted such civil
      commitment laws. Some forensic evaluators of rapists base findings supporting
      such commitment on the diagnosis of paraphilia not otherwise specified, using
      this miscellaneous category as a substitute for a proposed diagnosis that was
      rejected for inclusion in the Diagnostic and Statistical Manual of Mental
      Disorders (DSM) in 1986. Despite the deliberate rejection of such a hypothesized
      rape paraphilia for DSM, and despite a continued lack of research supporting the
      validity or interrater reliability of such a diagnosis, it is widely used as a
      basis for confining rapists. This article discusses the history and ethics
      related implications of this forensic practice.

PMID- 19092063
TI  - The death penalty in Catholic teaching and medicine: intersections and places for
      dialogue.
AB  - Current debate on the death penalty in public and professional spheres is seen as
      divisive in nature, disallowing the possibility of common agreement. The history
      of views of the death penalty within the Catholic Church illustrates centuries of
      tensions and ambiguities as well as a current posture that manages to hold these
      tensions while advocating a strong position. That history of church views itself
      contains allusions to and intersections with medicine. There is something
      tangible to be gained in understanding religious views on the death penalty, in
      the debates both within medicine and in the public sphere. An argument is made
      for sufficient overlap of contemporary purpose between the goals of church and
      medicine to warrant further dialogue in enhanced and deliberative democratic
      processes.

PMID- 19092064
TI  - Commentary: further points for dialogue on the death penalty, the church, and our
      profession.
AB  - The invitation to dialogue on the subject of the death penalty is both important
      for our time and challenging in what it calls forth from us. It forces us to
      recognize both the fundamental privacy of individual intention and the potential
      breadth of its reach. It can deepen our sense of responsibility for what happens
      to others on our account, even in the apparent absence of intention. The
      astonishing power of the spoken word should be harnessed by cooperative dialogue
      to focus its consequences more sharply on the demands of justice. We need
      dialogue to attend faithfully to our deepest obligations and longings.

PMID- 19092065
TI  - Commentary: the cost of converting religious morals into politics.
AB  - Theologically informed positions are grounded in core beliefs and may be
      rationally discussed. We analyze Dr. Norko's suggestion on how, in the public
      square, to address moral disagreements. We point out the dangers of "deliberative
      democracy" as an approach to resolving conflicts over basic values. We suggest an
      alternative approach, better grounded in reason, as a way of bringing religious
      and secular views into a discussion of the death penalty.

PMID- 19092066
TI  - Functional MRI lie detection: too good to be true?
AB  - Neuroscientists are now applying a 21st-century tool to an age-old question: how
      can you tell when someone is lying? Relying on recently published research, two
      start-up companies have proposed to use a sophisticated brain-imaging technique,
      functional magnetic resonance imaging (fMRI), to detect deception. The new
      approach promises significantly greater accuracy than the conventional polygraph-
      at least under carefully controlled laboratory conditions. But would it work in
      the real world? Despite some significant concerns about validity and reliability,
      fMRI lie detection may in fact be appropriate for certain applications. This new
      ability to peer inside someone's head raises significant questions of ethics.
      Commentators have already begun to weigh in on many of these questions. A wider
      dialogue within the medical, neuroscientific, and legal communities would be
      optimal in promoting the responsible use of this technology and preventing
      abuses.

PMID- 19092067
TI  - Commentary: functional MRI lie detection.
AB  - Functional brain imaging with magnetic resonance is a useful research tool for
      showing regional metabolic changes with ongoing brain activity. Use of functional
      imaging to study the anatomy and function of various brain areas has recently
      been applied to the examination of the emotional life of patients including those
      with anxiety, panic, or depression. The application of this technology to the
      complex problem of lie detection is the subject of an article by Joseph R.
      Simpson, MD, PhD, in this issue of The Journal. The present article concludes
      that the use of functional imaging to discriminate truth from lies does not meet
      the Daubert criteria for courtroom testimony.

PMID- 19092068
TI  - Commentary: the future of forensic functional brain imaging.
AB  - In "Functional MRI Lie Detection: Too Good to be True?" in this issue of The
      Journal, Joseph Simpson reviews the merits and the limitations of using fMRI to
      detect deception. After presenting the gaps in experimental data that stand in
      the way of translating the laboratory proof of concept to a field application,
      Simpson surveys the legal, regulatory and ethics concerns facing fMRI, should it
      emerge as a technologically robust method of lie detection. In our commentary, we
      update and interpret the data described by Simpson, from the points of view of an
      experimental scientist and a forensic clinician. We conclude that the current
      research funding and literature are prematurely skewed toward discussion of
      existing findings, rather than generation of new fMRI data on deception and
      related topics such as mind-reading, consciousness, morality, and criminal
      responsibility. We propose that further progress in brain imaging research may
      foster the emergence of a new discipline of forensic MRI.

PMID- 19092069
TI  - Forensic evaluation of problematic Internet use.
AB  - Problematic Internet use appears to be a growing concern in many criminal and
      civil legal proceedings. Problems range from inappropriate personal use of the
      Internet in the workplace and excessive use of online games, pornography, and
      gambling, to cyberbullying among children and adolescents and numerous forms of
      criminal activity. Forensic psychiatric evaluations may help courts or other
      agencies to understand individual cases and to discern whether a psychiatric
      disability may be involved. Furthermore, the forensic psychiatrist may be asked
      to formulate a prognosis or to suggest which treatments may be helpful. Among the
      multiple underlying pathophysiologic mechanisms that explain problematic Internet
      use are: addiction, compulsion, impulse-control problems, and mood disorders.
      There is no definitive or standard treatment protocol for evaluation or treatment
      of problematic Internet use per se. A comprehensive evaluation should address the
      underlying psychopathology or personal problems that prompt or contribute to the
      problematic Internet use. This article suggests approaches that may help forensic
      psychiatrists to conduct a thorough evaluation with reasonable treatment
      recommendations. Different formulations of the problem and a discussion of DSM-IV
      factors are offered to provide starting points for the evaluation and to help
      psychiatrists to understand how problematic Internet use may relate to Axis I
      disorders or other factors.

PMID- 19092070
TI  - Factors associated with agreement between experts in evidence about psychiatric
      injury.
AB  - Psychiatrists and psychologists acting as expert witnesses in court cases are
      often accused of bias or error. We examined the level of agreement and factors
      influencing agreement between expert reports admitted into evidence during
      adversarial civil proceedings. The inter-rater reliability of the psychiatric
      diagnosis was examined in 51 pairs of civil medicolegal reports written by
      experts engaged by the same side and 97 pairs of experts engaged by opposite
      sides. Reports written by experts engaged by the same adversarial side had good
      agreement about the presence of a mental disorder (kappa = .74) but had only fair
      agreement about the specific psychiatric diagnosis (average kappa = .31). Reports
      written by experts engaged by opposing adversarial sides had poor agreement about
      the presence of any mental disorder and also the specific psychiatric diagnosis.
      Experts were more likely to agree about the presence of a mental disorder if the
      plaintiff was involved in a fatal accident. The agreement of treating doctors and
      experts was similar to that of pairs of experts.

PMID- 19092071
TI  - Jackson's Indiana: state hospital competence restoration in Indiana.
AB  - Restoration to competence (RTC) of mentally disordered defendants has become
      increasingly important for state hospitals. In Indiana, most RTC admissions are
      sent to one primarily forensic state hospital, but many are admitted to other
      state hospitals. A state database of defendants admitted for RTC between 1988 and
      2005 was analyzed for trends in annual admissions, length of stay (LOS), and
      success of restoration by hospital and by diagnostic category. Regression models
      were developed to identify factors associated with RTC success. Analysis of 1,475
      RTC admissions showed increased annual admissions over the study period. While
      the forensic hospital restored a higher percentage of individuals than the other
      state hospitals, the percentage of RTC success decreased over time in all
      hospitals. Admission to the forensic hospital, female gender, and mood disorder
      diagnosis were associated with increased restoration success. Older age and
      psychotic disorder or mental retardation diagnoses were associated with decreased
      likelihood of restoration. Race was not significantly associated with RTC at six
      months, but white defendants were less likely to be restored within one year.

PMID- 19092072
TI  - The CHESS method of forensic opinion formulation: striving to checkmate bias.
AB  - Expert witnesses use various methods to render dispassionate opinions. Some
      forensic psychiatrists acknowledge bias up front; other experts use principles
      endorsed by the American Academy of Psychiatry and the Law or other professional
      organizations. This article introduces CHESS, a systematic method for reducing
      bias in expert opinions. The CHESS method involves identifying a Claim or
      preliminary opinion; developing a Hierarchy of supporting evidence; examining the
      evidence for weaknesses or areas of Exposure; Studying and revising the claim and
      supporting evidence; and Synthesizing a revised opinion. Case examples illustrate
      how the CHESS method may help experts reduce bias while strengthening opinions.
      The method also helps experts prepare for court by reminding them to anticipate
      questions that may be asked during cross-examination. The CHESS method provides a
      framework for formulating, revising, and identifying limitations of opinions,
      which allows experts to incorporate neutrality into forensic opinions.

PMID- 19092073
TI  - Addressing the perfect phantom on the witness stand.
AB  - When expert witnesses are cross-examined, a common gambit of opposing counsel is
      to create a phantom for comparison purposes. The constructed phantom is typically
      portrayed as an individual who has gone through similar, difficult life
      circumstances without the impairments or problematic behavioral sequelae of the
      plaintiff or defendant in the trial. Abuse histories, assaults, and traumatic
      experiences all are posited to have little effect on this phantom other, an
      invulnerability that leads us to call this construct the Perfect Phantom. In this
      article, the nature of the Perfect Phantom cross-examination is described, along
      with strategies for coping with these questions.

PMID- 19092074
TI  - School shooting as a culturally enforced way of expressing suicidal hostile
      intentions.
AB  - Suicide with hostile intent encompasses a wide range of behaviors, from self
      killing by methods that can harm others, to the suicide that generally follows a
      spree-killing raid. Reports on school shooting, a highly dangerous and lethal
      behavior that is spreading from North America to European countries, are analyzed
      within the paradigm of suicide with hostile intent, with the purpose of
      discovering some elements that might prevent and limit the dissemination of this
      behavior by imitation. In school shooting, the perpetrators often register a
      message before their killing raid, as in an ancient form of suicidal assault, the
      devotio, that was widespread across ancient Mediterranean Roman, Greek, and
      Hebrew cultures. The development of a code of rules to report on these episodes,
      likely to attract the interest of the population for their bloody implications,
      could prevent the dissemination of cultural norms that encourage this behavior.

PMID- 19092075
TI  - Pro se competence in the aftermath of Indiana v. Edwards.
AB  - The right to represent oneself at trial is well-established, but not absolute.
      Recently, in Indiana v. Edwards, the United States Supreme Court considered
      whether states may demand a higher standard of competence for criminal defendants
      seeking to represent themselves at trial than that necessary for standing trial
      with attorney representation. Ultimately, the Court ruled that the Constitution
      allows states to employ a higher competency standard for pro se defendants. In
      this analysis of the Court's decision, the authors describe the facts of this
      case, the legal precedents framing the issues facing the Court, and the Court's
      rationale for its opinion. The ruling is considered in light of available
      research involving pro se defendants and whether this ruling is consistent with
      professional guidelines related to forensic psychiatric practice. Implications of
      the decision for forensic clinicians and limitations of the decision are
      discussed.

PMID- 19092076
TI  - AAPL guideline for forensic evaluation of psychiatric disabilities: a disability
      law perspective.
AB  - Contemporary disability law takes into account the insight that physical and
      mental conditions need not be disabling but for the environmental and attitudinal
      barriers that keep people with disabilities from social participation on a plane
      of equality with others. The need to use a wheelchair does not disable except for
      curbs and stairs, and many mental conditions do not disable except for social
      attitudes. The "AAPL Guideline for Forensic Evaluation of Psychiatric
      Disabilities" is a refreshing departure from writings that approach disability
      from a perspective that focuses on nothing but medical considerations and the
      study of how individuals are defective compared with established norms. The
      Guideline stresses the process of examination and list important legal
      considerations for examiners to apply. But the Guideline does not show any
      awareness of a model of disability other than a medical one that classifies
      individuals by defect. Psychiatrists would do well to consider the role of social
      barriers when using the Guideline in making disability-related examinations.

PMID- 19092077
TI  - "Filled with desperation": psychotherapy with an insanity acquittee.

PMID- 19092078
TI  - Commentary: psychotherapy in a forensic hospital.
AB  - Very little is written in American forensic journals about psychodynamic
      psychotherapy for patients committed to forensic hospitals. Relatively little is
      known of the process of helping these patients cope with their mental illnesses,
      to gain insight into their crimes and their unconscious dynamics, or simply to
      cope with the dreary landscape of the forensic maximum-security institution. In
      this commentary, the author hopes to shed light on some of those processes.

PMID- 19092079
TI  - Commentary: on walking and talking.
AB  - I welcome Dr. Kapoor's reflections on psychotherapy with offender patients. In
      this commentary, I will discuss the value of psychodynamic psychotherapy in the
      treatment of forensic patients and some of the technical competencies required. I
      hope that these thoughts, and Dr. Kapoor's fine writing, will inspire other
      forensic practitioners to practice psychodynamic forensic psychiatry and to
      utilize psychodynamic ideas in both their formulations and their conversations
      with patients.

PMID- 19092080
TI  - Criminal background checks for psychiatry? Michigan's mental health
      exceptionalism.

PMID- 19092081
TI  - Can a newer MR contrast agent be used to monitor disease progression in muscular
      dystrophy?

PMID- 19092086
TI  - Moderate versus mediocre: the reliability of spine MR data interpretations.

PMID- 19092087
TI  - Barium studies in modern radiology: do they have a role?

PMID- 19092088
TI  - Industrial-academic research relationships: departmental collaborations.

PMID- 19092089
TI  - MR imaging insights into skeletal maturation: what is normal?
AB  - Skeletal growth and maturation in children is a dynamic process that can be
      documented with magnetic resonance (MR) imaging. There are predictable normal
      developmental changes that must be differentiated from pathologic processes. This
      review discusses the histologic structure and MR imaging appearance of normal
      development-related changes of the musculoskeletal system in children, including
      those that may be mistaken for abnormalities.

PMID- 19092090
TI  - Determination of regional ejection fraction in patients with myocardial
      infarction by using merged late gadolinium enhancement and cine MR: feasibility
      study.
AB  - PURPOSE: To quantify regional ejection fraction (EF) in patients with myocardial
      infarction (MI) by using merged late gadolinium enhancement (LGE) and cine
      magnetic resonance (MR) imaging, and compare this method with the standardized 17
      segment American Heart Association approach. MATERIALS AND METHODS: After
      institutional review board approval and informed consent, 15 MI patients (14 men,
      one woman; mean age, 63 years +/- 10 [standard deviation]) were studied at 1 week
      and at 4 months after MI. Short-axis LGE MR information was used to quantify
      infarct size, and to divide the left ventricle (LV) on short-axis cine MR images
      in infarct, periinfarct, and remote regions by using a fixed-center method,
      yielding information on regional volumes, regional EFs, systolic wall thickening
      (SWT), and systolic wall motion (SWM). This approach was compared with a floating
      center approach and the 17-segment approach. RESULTS: Mean infarct size
      (normalized to LV mass) was 25% +/- 14 at 1 week and 16% +/- 8 at 4 months (P <
      .001). At 4 months, LV EF significantly improved (mean, 47.9% +/- 5.9 vs 50.9% +/
      6.6, P = .031), matching an improvement of regional EF (mean, 17.1% +/- 11.5 vs
      24.6% +/- 13.1, P = .005) and SWM (mean, 3.2 mm +/- 1.7 vs 3.9 mm +/- 2.1, P =
      .027) in the infarcted myocardium. No significant changes in regional EF, SWT, or
      SWM occurred in the remote myocardium. Regional EF estimates correlated well with
      SWT and SWM (both r = 0.92, P < .001). The floating-center method invariably
      underestimated regional EF (mean, -20.8% +/- 7.6; 95% confidence interval: 
      23.7%, -17.9%), especially with increasing infarct size. By using the 17-segment
      approach, no functional improvement was shown in the infarcted myocardium.
      CONCLUSION: Assessment of regional ventricular performance (regional EF) in well
      defined areas (eg, infarcted and remote myocardium) is feasible by using merged
      LGE and cine MR imaging.

PMID- 19092091
TI  - Nephrotoxicity of iso-osmolar iodixanol compared with nonionic low-osmolar
      contrast media: meta-analysis of randomized controlled trials.
AB  - PURPOSE: To compare the nephrotoxicity of iso-osmolar iodixanol with that of
      nonionic low-osmolar contrast media (CM) (LOCM) in randomized clinical trials.
      MATERIALS AND METHODS: This meta-analysis was conducted with a systematic search
      of MEDLINE, EMBASE, BIOSIS, Web of Science, ISI Web of Knowledge, Current
      Contents Medizin, Cochrane Library (until August 2007), trial registers,
      conference proceedings, and reference lists to identify studies and with requests
      from all manufacturers of CM for unidentified studies. Randomized controlled
      trials assessing serum creatinine levels before and after intravascular
      application of iodixanol or LOCM were included. The primary outcome measures were
      the incidence of contrast medium-induced nephropathy (CIN) and change in serum
      creatinine levels. RESULTS: Twenty-five trials were included. Iodixanol did not
      significantly reduce the risk of CIN (relative risk [RR], 0.80; 95% confidence
      interval [CI]: 0.61, 1.04; weighted mean difference in serum creatinine increase,
      0.01 mg/dL [0.88 mumol/L]; 95% CI: -0.01, 0.03). There was no significant risk
      reduction after intravenous administration of the CM (RR, 1.08; 95% CI: 0.62,
      1.89); subgroup with preexisting renal insufficiency (RR, 1.07; 95% CI: 0.56,
      2.02) or after intraarterial administration (RR, 0.68; 95% CI: 0.46, 1.01);
      subgroup with preexisting renal insufficiency (RR, 0.59; 95% CI: 0.33, 1.07).
      However, in patients with intraarterial administration and renal insufficiency,
      the risk of CIN was greater for iohexol than for iodixanol (RR, 0.38; 95% CI:
      0.21, 0.68), whereas there was no difference between iodixanol and the other
      (noniohexol) LOCM (RR, 0.95; 95% CI: 0.50, 1.78). CONCLUSION: Iodixanol is not
      associated with a significantly reduced risk of CIN compared with the LOCM pooled
      together. However, in patients with intraarterial administration and renal
      insufficiency, iodixanol is associated with a reduced risk of CIN compared with
      iohexol, whereas no significant difference between iodixanol and other LOCM could
      be found.

PMID- 19092092
TI  - Quantification of liver fat content: comparison of triple-echo chemical shift
      gradient-echo imaging and in vivo proton MR spectroscopy.
AB  - PURPOSE: To validate a triple-echo gradient-echo sequence for measuring the fat
      content of the liver, by using hydrogen 1((1)H) magnetic resonance (MR)
      spectroscopy as the reference standard. MATERIALS AND METHODS: This prospective
      study was approved by the appropriate ethics committee, and written informed
      consent was obtained from all patients. In 37 patients with type 2 diabetes (31
      men, six women; mean age, 56 years), 3.0-T single-voxel point-resolved (1)H MR
      spectroscopy of the liver (Couinaud segment VII) was performed to calculate the
      liver fat fraction from the water (4.7 ppm) and methylene (1.3 ppm) peaks,
      corrected for T1 and T2 decay. Liver fat fraction was also computed from triple
      echo (consecutive in-phase, opposed-phase, and in-phase echo times) breath-hold
      spoiled gradient-echo sequence (flip angle, 20 degrees), by estimating T2* and
      relative signal intensity loss between in- and opposed-phase values, corrected
      for T2* decay. Pearson correlation coefficient, Bland-Altman 95% limit of
      agreement, and Lin concordance coefficient were calculated. RESULTS: Mean fat
      fractions calculated from the triple-echo sequence and (1)H MR spectroscopy were
      10% (range, 0.7%-35.6%) and 9.7% (range, 0.2%-34.1%), respectively. Mean T2* time
      was 14.7 msec (range, 5.4-25.4 msec). Pearson correlation coefficient was 0.989
      (P < .0001) and Lin concordance coefficient was 0.988 (P < .0001). With the Bland
      Altman method, all data points were within the limits of agreement. CONCLUSION: A
      breath-hold triple-echo gradient-echo sequence with a low flip angle and
      correction for T2* decay is accurate for quantifying fat in segment VII of the
      liver. Given its excellent correlation and concordance with (1)H MR spectroscopy,
      this triple-echo sequence could replace (1)H MR spectroscopy in longitudinal
      studies.

PMID- 19092093
TI  - Distribution of renal tumor growth rates determined by using serial volumetric CT
      measurements.
AB  - PURPOSE: To retrospectively determine the distribution of growth rates across
      different sizes and subtypes of renal cortical tumors by assessing tumor volume
      and maximum tumor diameter at serial volumetric computed tomographic (CT)
      examinations. MATERIALS AND METHODS: The institutional review board approved this
      retrospective, HIPAA-compliant study. Fifty-three of 2304 patients (34 men, 19
      women; mean age, 67 years +/- 10 [standard deviation; range, 39-88 years) who
      underwent nephrectomy from 1989 to 2006 did not receive preoperative chemotherapy
      or radiation therapy and underwent at least two preoperative contrast material
      enhanced CT examinations (at least 3 months apart) with identical section
      thickness that was no more than one-fifth of longitudinal tumor diameter. Tumor
      volume and maximum diameter were measured on CT scans. Reciprocal of doubling
      time (DT) (RDT) was calculated. Analysis of variance and Student t tests were
      performed. RESULTS: Thirty-two clear cell carcinomas, 10 papillary carcinomas,
      six chromophobe carcinomas, four oncocytomas, and one angiomyolipoma were
      analyzed. Median tumor size was 2.9 cm (range, 1-12 cm). Seven tumors did not
      increase in volume. DT ranged from -78476.54 to 18057.43 days (mean, -1230.73
      days; median, 590.51 days). [corrected] Growth rate determined by using maximum
      diameter ranged from -10.8 to 33.2 mm/y (mean, 5.1 mm/y; median, 3.5 mm/y).
      Faster-growing tumors were more likely to be clear cell carcinomas, those of
      higher grade had higher growth rates. No significant correlation was found
      between RDT and tumor initial volume, subtype, or grade. Small renal tumors
      (<or=3.5 cm) were similar to larger tumors in subtype and growth rate. Age at
      diagnosis correlated negatively with renal tumor growth rate (P = .03).
      CONCLUSION: Growth rates in renal tumors of different sizes, subtypes, and grades
      represent a wide range and overlap substantially. Small renal tumors appear to be
      similar to larger ones in nature.

PMID- 19092095
TI  - Can cortical thickness asymmetry analysis contribute to detection of at-risk
      mental state and first-episode psychosis? A pilot study.
AB  - PURPOSE: To investigate whether cortical thickness analysis in individuals with
      an at-risk mental state (ARMS) might contribute to early detection of psychosis.
      MATERIALS AND METHODS: Ethics committee approval and written informed consent
      were obtained. Cortical thickness was analyzed because early disease-related
      morphometric changes were expected to be most pronounced in the cerebral cortex.
      With the assumption of progressive change in cortical thickness from control
      subjects, to those with an ARMS, and then to those who have had a first episode
      (FE) of psychosis, the brain regions that substantially differ between those with
      FE psychosis and control subjects were identified. Whether these regions help
      discriminate between the ARMS group and control subjects was tested. Because
      normal interindividual variation of cortical thickness, even for control
      subjects, may exceed that expected with early disease-related changes,
      intraindividual cortical thickness asymmetry was analyzed. Twenty age- and sex
      matched individuals for each group (ARMS group, FE group, and control subjects)
      were recruited within a prospective early-detection study. High-spatial
      resolution magnetization-prepared rapid gradient-echo magnetic resonance (MR)
      brain images were acquired with a 1.5-T MR imager. Cortical thickness asymmetry
      was analyzed in 41 anatomic regions corresponding to the Talairach standard brain
      atlas. RESULTS: Direct cortical thickness analysis did not help distinguish
      between groups. Cortical thickness asymmetry analysis helped distinguish between
      groups (P = .007); variability increased from control subjects, to the ARMS
      group, and then to the FE group in seven anatomic regions (P < .0001). Cortical
      thickness asymmetry in these regions helped distinguish the FE group from control
      subjects (P = .0006; sensitivity, 70.0%; specificity, 85.0%) and showed a trend
      toward helping to distinguish the ARMS group from control subjects (P = .06;
      sensitivity, 75.0%; specificity, 65.0%). CONCLUSION: Cortical thickness asymmetry
      analysis is more accurate than direct cortical thickness measurement in
      distinguishing the control from the FE group and might contribute to early
      detection of an ARMS.

PMID- 19092094
TI  - Whole-brain perfusion CT performed with a prototype 256-detector row CT system:
      initial experience.
AB  - PURPOSE: To preliminarily evaluate the feasibility and potential diagnostic
      utility of whole-brain perfusion computed tomography (CT) performed with a
      prototype 256-detector row CT system over an extended range covering the entire
      brain to assess ischemic cerebrovascular disease. MATERIALS AND METHODS:
      Institutional review board approval and informed consent were obtained. Eleven
      cases in 10 subjects (six men, four women; mean age, 64.3 years) with intra- or
      extracranial stenosis were retrospectively evaluated with whole-brain perfusion
      CT. Three readers independently evaluated perfusion CT data. The diagnostic
      performance of perfusion CT was visually evaluated with a three-point scale used
      to assess three factors. Differences between four axial perfusion CT images
      obtained at the basal ganglia level (hereafter, four-section images) and whole
      brain perfusion CT images were assessed with the paired t test. In four subjects,
      the interval between perfusion CT and single photon emission computed tomography
      (SPECT) was 1-17 days (mean, 10.3 days). Correlation between perfusion CT
      findings and SPECT findings was assessed with the Spearman correlation
      coefficient. RESULTS: Three-dimensional perfusion CT images and axial, coronal,
      and sagittal whole-brain perfusion CT images were displayed, and the extent of
      ischemia was assessed. Mean visual evaluation scores were significantly higher
      for whole-brain images than for four-section images (4.27 +/- 0.76 [standard
      deviation] vs 2.55 +/- 0.87). The cerebral blood flow ratios of the ischemic
      lesions relative to normal regions scanned with perfusion CT (x) and SPECT (y)
      showed a significant positive correlation (R(2) = 0.76, y = 0.44 x + 0.37, P <
      .001). CONCLUSION: Perfusion CT performed with a 256-detector row CT system can
      be used to assess the entire brain with administration of one contrast medium
      bolus. Thus, ischemic regions can be identified with one examination, which has
      the potential to improve diagnostic utility.

PMID- 19092096
TI  - Unenhanced flow-independent MR venography by using signal targeting alternative
      radiofrequency and flow-independent relaxation enhancement.
AB  - The purpose of this study was to provide the initial description of the signal
      targeting using alternative radiofrequency and flow-independent relaxation
      enhancement (STARFIRE) technique and demonstrate clinical feasibility by imaging
      the deep and superficial veins of the lower extremities in a small cohort of
      healthy subjects and patients with peripheral venous disease. STARFIRE is a flow
      independent technique for unenhanced magnetic resonance (MR) angiography. An
      adiabatic inversion pulse is applied to all spins on alternative acquisitions
      followed by complex subtraction. Blood vessels appear bright with uniform
      suppression of fat and muscle signals. Following approval by the hospital
      institutional review board and with written, informed consent, six healthy
      patients and four with peripheral venous disease were studied. The results
      demonstrate the clinical feasibility of STARFIRE to depict the deep and
      superficial venous systems of the lower extremities, and suggest the need for
      addition clinical evaluation.

PMID- 19092097
TI  - Routine use of positive oral contrast material is not required for oncology
      patients undergoing follow-up multidetector CT.
AB  - The purpose of this retrospective medical audit was to evaluate the effect of
      discontinuing routine administration of oral contrast material to oncology
      patients undergoing follow-up multidetector computed tomography (CT) on reader
      evaluation of study adequacy. Analysis of 100 patients' experience of CT shows
      that positive oral contrast material was their least pleasant experience (P <
      .0001). Abandoning the routine use of positive oral contrast material for follow
      up scans in general oncology patients undergoing multidetector CT, with section
      reconstruction thickness of 2.5 mm, was audited for 447 patents and included 5-13
      month follow-up. The patient satisfaction study and clinical audit were performed
      according to local institutional audit guidelines. Since this was a clinical
      audit project, ethical approval was not required under UK National Health Service
      research governance arrangements. No patient needed to be recalled, no related
      diagnostic error has been reported, and follow-up CT, available in 285 of 447
      cases (64%), revealed no error on the audited scan. We conclude that the routine
      use of positive oral contrast material is unnecessary for follow-up multidetector
      CT for general oncology indications.

PMID- 19092098
TI  - Modified prostate volume algorithm improves transrectal US volume estimation in
      men presenting for prostate brachytherapy.
AB  - PURPOSE: To evaluate the accuracy of the conventional transrectal
      ultrasonographic (US) prostate volume formula and determine whether a more
      accurate volume formula, calculated on the basis of prostate shape as observed at
      planimetry, can be described for the majority of prostate glands. MATERIALS AND
      METHODS: This retrospective study was institutional review board approved, with
      waiver of informed consent. A total of 138 consecutive patients who underwent
      prostate brachytherapy were included for analysis. Prostate volume was estimated
      by using the conventional prolate ellipsoid formula (length x height x width x
      [pi/6]). A reference standard for prostate volume was calculated by using
      planimetry. The mean prostate shape was assessed by using three-dimensional
      volume-rendering of the planimetric images. The prostate shapes were evaluated to
      determine the best-fit mathematic formula for accurate volume estimation.
      Statistical analyses were performed by using Pearson correlation, paired Student
      t test, Bland-Altman plots, and concordance correlation coefficient. RESULTS:
      Planimetric data showed the majority of prostate glands to be more bullet-shaped
      than ellipsoid. Only 13.3% of volumes determined by using the conventional
      prolate ellipsoid formula were within 10% of the planimetric volume. The prolate
      ellipsoid formula underestimated volume by 17% on average (95% confidence
      interval: 14%, 19%). A mathematic formula representing a bullet shape (length x
      height x width x [pi/4.8]) was determined to best represent the majority of
      prostate glands presented for brachytherapy; 75% of volumes were within 10% of
      planimetric volume by using this formula. Concordance correlation coefficient
      increased from 0.87 to 0.95. Formula accuracy was particularly improved in
      prostate glands smaller than 55 cm(3) (P = .14). CONCLUSION: A modified prostate
      volume formula that closely represents the shape of the prostate smaller than 55
      cm(3) demonstrated improved volume measurement accuracy compared with the prolate
      ellipsoid formula used in men presenting for brachytherapy.

PMID- 19092099
TI  - Repeated transarterial chemoembolization in the treatment of liver metastases of
      colorectal cancer: prospective study.
AB  - PURPOSE: To evaluate local tumor control and survival data after transarterial
      chemoembolization with different drug combinations in the palliative treatment of
      liver metastases in patients with colorectal cancer. MATERIALS AND METHODS: The
      study was approved by institutional review board, and informed consent was
      obtained from all patients included in the study. A total of 463 patients (mean
      age, 62.5 years; range, 34.7-88.1 years) with unresectable liver metastases of
      colorectal cancer that did not respond to systemic chemotherapy were repeatedly
      treated with chemoembolization in 4-week intervals. In total, 2441
      chemoembolization procedures were performed (mean, 5.3 sessions per patient). Of
      463 patients, 67.4% had multiple (five or more) metastases, 8% had one
      metastasis, 10.4% had two metastases, and 14.3% had three or four metastases. The
      local chemotherapy protocol consisted of mitomycin C alone (n = 243), mitomycin C
      with gemcitabine (n = 153), or mitomycin C with irinotecan (n = 67). Embolization
      was performed with lipiodol and starch microspheres for vessel occlusion. Tumor
      response was evaluated with magnetic resonance imaging. The change in tumor size
      was calculated and the response was evaluated according to the Response
      Evaluation Criteria in Solid Tumors. Survival rates from first diagnosis and from
      first chemoembolization session were calculated according to the Kaplan-Meier
      method. Follow-up imaging was performed until patient death. RESULTS: Evaluation
      of local tumor control resulted in partial response (68 patients [14.7%]), stable
      disease (223 patients [48.2%]), and progressive disease (172 patients [37.1%]).
      The 1-year survival rate after chemoembolization was 62%, and the 2-year survival
      rate was 28%. Median survival from date of diagnosis of liver metastases was 38
      months and from the start of chemoembolization treatment was 14 months. There was
      no statistically significant difference between the three treatment protocols.
      CONCLUSION: Chemoembolization is a minimally invasive therapy option for
      palliative treatment of liver metastases in patients with colorectal cancer, with
      similar results among three chemoembolization protocols.

PMID- 19092101
TI  - Case 141: superficial siderosis.

PMID- 19092102
TI  - Iso- versus low-osmolar contrast media and contrast medium-induced nephropathy.

PMID- 19092103
TI  - Which is the real determinant of MR angiography image quality: dose or injection
      protocol?

PMID- 19092104
TI  - Drawbacks of the simplified imaging approach for evaluation of the solid renal
      mass in adults.

PMID- 19092105
TI  - Jellinek Memorial Fund.

PMID- 19092106
TI  - Memantine induces reversible neurologic impairment in patients with MS.
AB  - BACKGROUND: Cognitive dysfunction is very common in multiple sclerosis (MS) and
      it severely impairs patients' quality of life. Thus, we explored whether
      memantine might improve cognitive performance in patients with MS. METHODS: We
      conducted a pilot trial with memantine (30 mg/day) in patients with MS with
      cognitive impairment. The trial was designed as a 1-year, randomized, double
      blind, crossover study comparing memantine against a placebo in 60 patients with
      MS and cognitive impairment. Cognitive impairment was defined as the performance
      1.5 standard deviations below the normative data in at least two tests of two
      cognitive domains in the Brief Repeatable Battery-Neuropsychology. The primary
      endpoint was improvement of verbal memory and the secondary endpoints were safety
      and improvements in the other cognitive domains, disability and quality of life.
      The trial was registered at www.clinicaltrials.org: NCT00638833. RESULTS:
      Although 19 patients had been included, the trial was halted after nine patients
      reported a worsening of their neurologic symptoms that deteriorated their quality
      of life. Seven of the nine patients in the memantine arm had blurred vision,
      fatigue, severe headache, increased muscle weakness, walking difficulties, or
      unstable gait. Only two patients in the placebo group reported neurologic
      symptoms and in both cases they were related with changes in their disease
      modifying therapy. The adverse events only occurred on reaching the maximum dose
      (30 mg/day). After stopping medication, the patients reverted to their baseline
      disability within a few days. CONCLUSIONS: Memantine at a dose of 30 mg/day may
      induce transient worsening of neurologic symptoms of multiple sclerosis.

PMID- 19092107
TI  - Treatment effects for which shift or binary analyses are advantageous in acute
      stroke trials.
AB  - BACKGROUND: In acute stroke trials, functional outcome may be analyzed by
      dichotomizing ordinal outcome scales or by evaluating the entire scale range
      (shift analysis). The conditions under which shift or binary analysis will be
      more efficient have not been previously well delineated. METHODS: Model
      randomized clinical trials employing the modified Rankin Scale of global handicap
      were constructed to reflect 1) mild benefits experienced across all ranges of
      stroke severity (neuroprotective effect), 2) substantial benefits across all
      ranges of stroke severity (early recanalization effect), 3) substantial benefits
      across wide range of stroke severity but with limited ability to achieve fully
      normal outcome (late recanalization effect), 4) benefits clustered at unexpected
      health state transitions. RESULTS: In neuroprotective models, shift analysis was
      the most efficient technique in detecting a treatment effect. In the early
      recanalization models, dichotomization at excellent outcome and shift analysis
      were of comparable efficiency, both superior to dichotomization at good outcome.
      In the late recanalization models, dichotomization at good outcome performed
      best, shift analysis less well, and dichotomization at excellent outcome poorly.
      In the unexpected benefits model, shift analysis substantially outperformed
      dichotomization analyses. These patterns held among the seven actual acute trials
      reporting full range Rankin outcomes and showing treatment benefit identified in
      the literature. CONCLUSIONS: The pattern of treatment effect of the intervention
      determines whether shift analysis or simple dichotomized analysis will be more
      efficient. Shift analysis is especially advantageous when treatments confer a
      relatively uniform, mild benefit to patients over a wide range of stroke
      severities or confer benefits at unexpected but clinically important health state
      transitions.

PMID- 19092108
TI  - Skin blister and skin biopsy to quantify epidermal nerves: a comparative study.
AB  - BACKGROUND: Skin biopsy is an important procedure for the diagnosis of peripheral
      neuropathy. The main indicators of unmyelinated nerve involvement are decreased
      density and abnormal morphology of epidermal nerve fibers (ENFs). The suction
      skin blister is an alternative, less invasive method to visualize and quantify
      ENFs. The blister roof provides an integrated bird's eye view of all ENFs within
      one tissue specimen. OBJECTIVE: We compared the suction skin blister method to
      the punch skin biopsy for evaluation of ENFs. METHODS: Twenty-five volunteers, 35
      to 62 years old, without symptoms or history of peripheral neuropathy, and normal
      by neurologic examination and nerve conduction tests, were studied. One 3 mm
      punch biopsy and two 3 mm suction blister specimens were collected from the right
      foot and calf. Comparison between blister and biopsy ENF density was assessed by
      repeated measures analysis of covariance, accounting for age, gender, and
      specimen's location. RESULTS: The epidermal roof of the suction skin blister
      permitted detailed analyses of ENF density, morphology, and distribution across
      the epidermis and observation of ENF branching pattern. No systematic differences
      of ENF density were found between skin blisters and biopsies (p = 0.29) or
      between pairs of blisters from the same location (p = 0.15). ENF density was
      lower for older subjects (p < 0.01). CONCLUSIONS: The suction skin blister method
      has potential as a diagnostic tool to investigate small fiber neuropathies. It is
      a minimally invasive and reliable technique, comparable to skin biopsy for
      determining epidermal nerve fiber density.

PMID- 19092110
TI  - Hepatitis vaccines and pediatric multiple sclerosis: does timing or type matter?

PMID- 19092109
TI  - Yield of combined perfusion and diffusion MR imaging in hemispheric TIA.
AB  - OBJECTIVE: Transient ischemic attacks (TIA) predict future stroke. However, there
      are no sensitive and specific diagnostic criteria for TIA and interobserver
      agreement regarding the diagnosis is poor. Diffusion-weighted MRI (DWI)
      demonstrates acute ischemic lesions in approximately 30% of TIA patients; the
      yield of perfusion-weighted MRI (PWI) is unclear. METHODS: We prospectively
      performed both DWI and PWI within 48 hours of symptom onset in consecutive
      patients admitted with suspected hemispheric TIAs of <24 hours symptom duration.
      Two independent raters, blinded to clinical features, assessed the presence and
      location of acute DWI and PWI lesions. Lesions were correlated with suspected
      clinical localization and baseline characteristics. Clinical features predictive
      of a PWI lesion were assessed. RESULTS: Forty-three patients met the inclusion
      criteria. Thirty-three percent had a PWI lesion and 35% had a DWI lesion. Seven
      patients (16%) had both PWI and DWI lesions and 7 (16%) had only PWI lesions. The
      combined yield for identification of either a PWI or a DWI was 51%. DWI lesions
      occurred in the clinically suspected hemisphere in 93% of patients; PWI lesions
      in 86%. PWI lesions occurred more frequently when the MRI was performed within 12
      hours of symptom resolution, in patients with symptoms of speech impairment, and
      among individuals younger than 60 years. CONCLUSIONS: The combination of early
      diffusion-weighted MRI and perfusion-weighted MRI can document the presence of a
      cerebral ischemic lesion in approximately half of all patients who present with a
      suspected hemispheric transient ischemic attack (TIA). MRI has the potential to
      improve the accuracy of TIA diagnosis. ACA = anterior cerebral artery; CI =
      confidence interval; DWI = diffusion-weighted MRI; ICA = internal carotid artery;
      MCA = middle cerebral artery; MRA = magnetic resonance angiography; MTT = mean
      transit time; OR = odds ratios; PCA = posterior cerebral artery; PWI = perfusion
      weighted MRI; RR = risk ratios; TIA = transient ischemic attacks; TOAST = Trial
      of Org 10172 in Acute Stroke Treatment.

PMID- 19092111
TI  - Will tricyclic antidepressants make a comeback for depressed Parkinson disease
      patients?

PMID- 19092112
TI  - A controlled trial of antidepressants in patients with Parkinson disease and
      depression.
AB  - BACKGROUND: Parkinson disease (PD) is a common neurodegenerative disease
      affecting up to 1 million individuals in the United States. Depression affects up
      to 50% of these patients and is associated with a variety of poor outcomes for
      patients and their families. Despite this, there are few evidence-based data to
      guide clinical care. METHODS: An NIH-funded, randomized, controlled trial of
      paroxetine CR, nortriptyline, and placebo in 52 patients with PD and depression.
      The primary outcomes were the change in the Hamilton Depression Rating Scale (HAM
      D) and the percentage of depression responders at 8 weeks. RESULTS: Nortriptyline
      was superior to placebo for the change in HAM-D (p < 0.002); paroxetine CR was
      not. There was a trend for superiority of nortriptyline over paroxetine CR at 8
      weeks (p < 0.079). Response rates favored nortriptyline (p = 0.024):
      nortriptyline 53%, paroxetine CR 11%, placebo 24%. In planned contrasts of
      response rates, nortriptyline was superior to paroxetine CR (p = 0.034).
      Nortriptyline was also superior to placebo in many of the secondary outcomes,
      including sleep, anxiety, and social functioning, while paroxetine CR was not.
      Both active drug treatments were well tolerated. CONCLUSIONS: Though relatively
      modest in size, this is the largest placebo-controlled trial done to date in
      patients with Parkinson disease (PD) and depression. Nortriptyline was
      efficacious in the treatment of depression and paroxetine CR was not. When
      compared directly, nortriptyline produced significantly more responders than did
      paroxetine CR. The trial suggests that depression in patients with PD is
      responsive to treatment and raises questions about the relative efficacy of dual
      reuptake inhibitors and selective serotonin reuptake inhibitors.

PMID- 19092113
TI  - Identification of differentially expressed genes between cloned and zygote
      developing zebrafish (Danio rerio) embryos at the dome stage using suppression
      subtractive hybridization.
AB  - Comparative analyses of differentially expressed genes between somatic cell
      nuclear transfer (SCNT) embryos and zygote-developing (ZD) embryos are important
      for understanding the molecular mechanism underlying the reprogramming processes.
      Herein, we used the suppression subtractive hybridization approach and from more
      than 2900 clones identified 96 differentially expressed genes between the SCNT
      and ZD embryos at the dome stage in zebrafish. We report the first database of
      differentially expressed genes in zebrafish SCNT embryos. Collectively, our
      findings demonstrate that zebrafish SCNT embryos undergo significant
      reprogramming processes during the dome stage. However, most differentially
      expressed genes are down-regulated in SCNT embryos, indicating failure of
      reprogramming. Based on Ensembl description and Gene Ontology Consortium
      annotation, the problems of reprogramming at the dome stage may occur during
      nuclear remodeling, translation initiation, and regulation of the cell cycle. The
      importance of regulation from recipient oocytes in cloning should not be
      underestimated in zebrafish.

PMID- 19092115
TI  - Germ cell research: a personal perspective.
AB  - My interest in germ cells began when I first witnessed sea urchin fertilization
      and embryo development during a laboratory class at Hokkaido University, Sapporo,
      Japan, almost 60 yr ago. Weismann's concept of germ cells that I learned during
      my undergraduate years became the driving force of my entire research career.
      During the early years, my associates and I used mainly the golden hamster and
      the guinea pig as model animals because their spermatozoa had large acrosomes and
      we could readily follow changes in the acrosomes without killing or staining
      spermatozoa. We later used the mouse as our model organism because we wanted to
      produce live offspring with known genetic backgrounds. A summary of the findings
      we made during those years includes the following: (1) first in vitro sperm
      capacitation; (2) discovery of sperm hyperactivation; (3) demonstration of the
      importance of Ca(2+) in sperm acrosome reaction, hyperactivation, sperm-egg
      fusion, and egg activation; (4) development of the sperm's fusion competence
      during the acrosome reaction; (5) characterization of sperm-oviduct relationships
      before and during fertilization; (6) use of zona-free hamster eggs to examine
      fertilizing ability and chromosomes of human spermatozoa; (7) development and use
      of intracytoplasmic sperm injection; (8) use of prespermatozoal cells for the
      production of offspring; (9) sperm preservation by freeze-drying and freezing
      whole-animal bodies; and (10) mouse cloning by somatic cell nuclear transfer. My
      current interests and my visions for the future include the following: (1) mass
      production of mature eggs and spermatozoa in vitro, (2) permanent sperm
      preservation at ambient temperature, (3) development of safer and more efficient
      assisted fertilization (reproduction) technologies, (4) development of safe and
      efficient methods of cloning, (5) production of artificial organs such as an
      artificial uterus, (6) development of safe and effective male contraceptives, and
      (7) prevention of cancer through germ cell research.

PMID- 19092114
TI  - Developmental programming: differential effects of prenatal testosterone and
      dihydrotestosterone on follicular recruitment, depletion of follicular reserve,
      and ovarian morphology in sheep.
AB  - Prenatal testosterone excess programs an array of adult reproductive disorders
      including luteinizing hormone excess, functional hyperandrogenism, neuroendocrine
      defects, polycystic ovarian morphology, and corpus luteum dysfunction,
      culminating in early reproductive failure. Polycystic ovarian morphology
      originates from enhanced follicular recruitment and follicular persistence. We
      tested to determine whether prenatal testosterone treatment, by its androgenic
      actions, enhances follicular recruitment, causes early depletion of follicular
      reserve, and disrupts the ovarian architecture. Pregnant sheep were given twice
      weekly injections of testosterone or dihydrotestosterone (DHT), a nonaromatizable
      androgen, from Days 30 to 90 of gestation. Ovaries were obtained from Day-90 and
      Day-140 fetuses, and from 10-mo-old females during a synchronized follicular
      phase (n = 5-9 per treatment). Stereological techniques were used to quantify
      changes in ovarian follicle/germ cell populations. Results revealed no
      differences in numbers of oocytes and follicles between the three groups on Fetal
      Day 90. Greater numbers of early growing follicles were found in prenatal
      testosterone- and DHT-treated fetuses on Day 140. Increased numbers of growing
      follicles and reduced numbers of primordial follicles were found in 10-mo-old,
      prenatal testosterone-treated females, but not in those treated with DHT. Antral
      follicles of prenatal testosterone-treated females, but not those treated with
      DHT, manifested several abnormalities, which included the appearance of
      hemorrhagic and luteinized follicles and abnormal early antrum formation. Both
      treatment groups showed morphological differences in the rete ovarii. These
      findings suggest that increased follicular recruitment and morphologic changes in
      the rete ovarii of prenatal testosterone-treated females are facilitated by
      androgenic programming, but that postpubertal follicular growth, antral
      follicular disruptions, and follicular depletion largely occur through estrogenic
      programming.

PMID- 19092116
TI  - The novel epididymis-specific beta-galactosidase-like gene Glb1l4 is essential in
      epididymal development and sperm maturation in rats.
AB  - We describe a novel epididymis-specific cDNA named Glb1l4, which was isolated
      from rat epididymis by differential display of mRNAs. Glb1l4 cDNA contains 2607
      nucleotides and encodes a 637-amino acid protein with 50% similarity to mouse
      beta-galactosidase. The gene is located on chromosome 8q13, spanning 21 exons.
      Northern blot analysis reveals that Glb1l4 is specifically expressed in the caput
      region of epididymis and upregulated by androgen. A specific polyclonal antiserum
      against the N-terminal peptide of GLB1L4 has been produced. Western blot analysis
      and immunohistochemistry assay reveal that GLB1L4 is specifically expressed in
      the principal cells of the caput epididymis. Interestingly, its expression peaks
      at Postnatal Day 45 in mRNA level and at Postnatal Day 60 in protein level while
      the epididymis column cells undergo differentiation. Moreover, within this very
      period this secretory protein is confined inside the cell with a change of
      subcellular distribution pattern, which implies its important roles in the cell
      differentiation process. Only after the epididymal epithelium differentiation is
      completed and the spermatozoa enter the epididymal lumen is the GLB1L4 secreted
      into the luminal fluid and bound on the sperm head. Our results suggest that
      GLB1L4 may play various roles in principal cell differentiation and sperm
      maturation.

PMID- 19092117
TI  - Liver-kidney transplantation to cure atypical hemolytic uremic syndrome.
AB  - Atypical hemolytic uremic syndrome is often associated with mutations in genes
      encoding complement regulatory proteins and secondary disorders of complement
      regulation. Progression to kidney failure and recurrence with graft loss after
      kidney transplantation are frequent. The most common mutation is in the gene
      encoding complement factor H. Combined liver-kidney transplantation may correct
      this complement abnormality and prevent recurrence when the defect involves genes
      encoding circulating proteins that are synthesized in the liver, such as factor H
      or I. Good outcomes have been reported when surgery is associated with
      intensified plasma therapy. A consensus conference to establish treatment
      guidelines for atypical hemolytic uremic syndrome was held in Bergamo in December
      2007. The recommendations in this article are the result of combined clinical
      experience, shared research expertise, and a review of the literature and
      registry information. This statement defines groups in which isolated kidney
      transplantation is extremely unlikely to be successful and a combined liver
      kidney transplant is recommended and also defines those for whom kidney
      transplant remains a viable option. Although combined liver-kidney or isolated
      liver transplantation is the preferred therapeutic option in many cases, the
      gravity of risk associated with the procedure has not been eliminated completely,
      and assessment of risk and benefit requires careful and individual attention.

PMID- 19092118
TI  - Nephrotic syndrome due to an amyloidogenic mutation in fibrinogen A alpha chain.
AB  - We identified amyloid derived from a mutant fibrinogen A alpha chain associated
      with one of the hereditary amyloidoses by kidney biopsy. The recognition of
      molecular and etiologic diversity among amyloidoses has revolutionized the
      management of systemic amyloidosis and necessitates precision in amyloid typing.
      Pitfalls and recommendations for the differential diagnosis of renal amyloid and
      current standards of amyloid typing are briefly discussed. Diagnosis of the
      amyloidosis type must be based on identification of the chemical composition of
      the amyloid protein in deposits and not on clinical suspicion, laboratory tests,
      or genetic testing. A clinical correlation is required to support but not make a
      diagnosis of amyloid type. If a hereditary form is detected by amyloid protein
      typing, then molecular studies are indicated. Conversely, in cases in which DNA
      sequence indicates a mutant amyloid precursor protein, protein analysis of the
      deposits must provide the definitive evidence. Negative or inconclusive results
      must be investigated further by a reference laboratory with the capability of
      applying more sophisticated methods.

PMID- 19092119
TI  - Recruitment of podocytes from glomerular parietal epithelial cells.
AB  - Loss of a critical number of podocytes from the glomerular tuft leads to
      glomerulosclerosis. Even in health, some podocytes are lost into the urine.
      Because podocytes themselves cannot regenerate, we postulated that glomerular
      parietal epithelial cells (PECs), which proliferate throughout life and adjoin
      podocytes, may migrate to the glomerular tuft and differentiate into podocytes.
      Here, we describe transitional cells at the glomerular vascular stalk that
      exhibit features of both PECs and podocytes. Metabolic labeling in juvenile rats
      suggested that PECs migrate to become podocytes. To prove this, we generated
      triple-transgenic mice that allowed specific and irreversible labeling of PECs
      upon administration of doxycycline. PECs were followed in juvenile mice beginning
      from either postnatal day 5 or after nephrogenesis had ceased at postnatal day
      10. In both cases, the number of genetically labeled cells increased over time.
      All genetically labeled cells coexpressed podocyte marker proteins. In
      conclusion, we demonstrate for the first time recruitment of podocytes from PECs
      in juvenile mice. Unraveling the mechanisms of PEC recruitment onto the
      glomerular tuft may lead to novel therapeutic approaches to renal injury.

PMID- 19092120
TI  - Regeneration of glomerular podocytes by human renal progenitors.
AB  - Depletion of podocytes, common to glomerular diseases in general, plays a role in
      the pathogenesis of glomerulosclerosis. Whether podocyte injury in adulthood can
      be repaired has not been established. Here, we demonstrate that in the adult
      human kidney, CD133+CD24+ cells consist of a hierarchical population of
      progenitors that are arranged in a precise sequence within Bowman's capsule and
      exhibit heterogeneous potential for differentiation and regeneration. Cells
      localized to the urinary pole that expressed CD133 and CD24, but not podocyte
      markers (CD133+CD24+PDX- cells), could regenerate both tubular cells and
      podocytes. In contrast, cells localized between the urinary pole and vascular
      pole that expressed both progenitor and podocytes markers (CD133+CD24+PDX+) could
      regenerate only podocytes. Finally, cells localized to the vascular pole did not
      exhibit progenitor markers, but displayed phenotypic features of differentiated
      podocytes (CD133-CD24-PDX+ cells). Injection of CD133+CD24+PDX- cells, but not
      CD133+CD24+PDX+ or CD133-CD24- cells, into mice with adriamycin-induced
      nephropathy reduced proteinuria and improved chronic glomerular damage,
      suggesting that CD133+CD24+PDX- cells could potentially treat glomerular
      disorders characterized by podocyte injury, proteinuria, and progressive
      glomerulosclerosis.

PMID- 19092121
TI  - Phosphorus binders and survival on hemodialysis.
AB  - Although hyperphosphatemia is a risk factor for mortality, there are limited data
      on whether therapy with phosphorus binders affects survival. We analyzed a
      prospective cohort study of 10,044 incident hemodialysis patients using Cox
      proportional hazards analyses to compare 1-yr all-cause mortality among patients
      who were or were not treated with phosphorus binders. We performed intention-to
      treat analyses to compare patients who began treatment with phosphorus binders
      during the first 90 d after initiating hemodialysis (n = 3555) with those who
      remained untreated during that period (n = 5055). We also performed as-treated
      analyses that modeled phosphorus binder treatment as a time-dependent exposure.
      We compared survival in a subcohort of treated (n = 3186) and untreated (n =
      3186) patients matched by their baseline serum phosphate levels and propensity
      score of receiving phosphorus binders during the first 90 d. One-year mortality
      was 191 deaths/1000 patient-years at risk. Treatment with phosphorus binders was
      independently associated with decreased mortality compared with no treatment in
      the intention-to-treat, as-treated, and matched analyses. The results were
      independent of baseline and follow-up serum phosphate levels and persisted in
      analyses that excluded deaths during the first 90 d of hemodialysis. In summary,
      treatment with phosphorus binders is independently associated with improved
      survival among incident hemodialysis patients. Although confirmatory studies are
      needed in the dialysis setting, future placebo-controlled, randomized trials of
      phosphorus binders might focus on predialysis patients with chronic kidney
      disease and normal serum phosphate levels.

PMID- 19092123
TI  - Nocturnal hemodialysis improves erythropoietin responsiveness and growth of
      hematopoietic stem cells.
AB  - Nocturnal home hemodialysis (NHD) is associated with an increase in hemoglobin
      level. We hypothesized that NHD enhances the removal of toxins of hematopoietic
      progenitor cells (HPCs), thereby improving HPC growth and function. Among 16
      patients with ESRD, 2 mo of NHD nearly doubled Kt/V per session and significantly
      lowered both parathyroid hormone levels and serum phosphate concentration. In
      addition, treatment with NHD improved hemoglobin levels from 113 +/- 3 to 125 +/-
      4 g/L (P = 0.03) without altering erythropoietin requirements or iron status. To
      assess whether NHD may enhance removal of HPC toxins, we collected paired plasma
      samples from the same patient during treatment with conventional HD and NHD. In
      vitro, growth of erythroid (BFU-E) and granulocytic (CFU-GM) colonies was
      superior when cultured with NHD plasma compared with conventional HD plasma.
      Differential gene expression profiles obtained from peripheral blood and HPC
      colonies revealed similar upregulation of genes responsible for HPC mobilization
      and growth and production of red blood cells. In conclusion, the enhanced
      clearance by NHD is associated with an improvement in HPC growth and a
      coordinated increase in expression of genes relevant to production of red blood
      cells.

PMID- 19092122
TI  - Effect of membrane permeability on survival of hemodialysis patients.
AB  - The effect of high-flux hemodialysis membranes on patient survival has not been
      unequivocally determined. In this prospective, randomized clinical trial, we
      enrolled 738 incident hemodialysis patients, stratified them by serum albumin <
      or = 4 and >4 g/dl, and assigned them to either low-flux or high-flux membranes.
      We followed patients for 3 to 7.5 yr. Kaplan-Meier survival analysis showed no
      significant difference between high-flux and low-flux membranes, and a Cox
      proportional hazards model concurred. Patients with serum albumin < or = 4 g/dl
      had significantly higher survival rates in the high-flux group compared with the
      low-flux group (P = 0.032). In addition, a secondary analysis revealed that high
      flux membranes may significantly improve survival of patients with diabetes.
      Among those with serum albumin < or = 4 g/dl, slightly different effects among
      patients with and without diabetes suggested a potential interaction between
      diabetes status and low serum albumin in the reduction of risk conferred by high
      flux membranes. In summary, we did not detect a significant survival benefit with
      either high-flux or low-flux membranes in the population overall, but the use of
      high-flux membranes conferred a significant survival benefit among patients with
      serum albumin < or = 4 g/dl. The apparent survival benefit among patients who
      have diabetes and are treated with high-flux membranes requires confirmation
      given the post hoc nature of our analysis.

PMID- 19092125
TI  - First morning voids are more reliable than spot urine samples to assess
      microalbuminuria.
AB  - Measurement of urinary albumin excretion (UAE) in a 24-h collection is the gold
      standard method to determine the presence of microalbuminuria. We sought to
      compare more practical alternatives--measurement of urinary albumin concentration
      (UAC) or albumin:creatinine ratio (ACR)--in a first morning void or in a spot
      urine sample with this gold standard. We asked 241 participants of a prospective
      cohort study to make three 24-h urine collections, a first morning void, and a
      spot urine sample. Regression analysis showed that the ACR in a first morning
      void best agreed with 24-h UAE. The prevalence of microalbuminuria determined by
      data from a first morning void (7.5%, whether by UAC or ACR) nearly equaled the
      prevalence of microalbuminuria determined by 24-h UAE (10.0%), whereas the
      prevalence was higher when determined by spot urine samples (25.4% for UAC and
      22.4% for ACR; both P < 0.001 versus 24-h UAE). The intraindividual coefficients
      of variation of the ACR in a first morning void and 24-h UAE were similar (19%).
      Intraindividual coefficients of variations of all other measurements of
      albuminuria were significantly greater. In conclusion, measurement of albuminuria
      in a first morning void, preferably as the ACR, is more reliable than a spot
      urine sample to diagnose and monitor microalbuminuria.

PMID- 19092124
TI  - Distinct functions of activated protein C differentially attenuate acute kidney
      injury.
AB  - Administration of activated protein C (APC) protects from renal dysfunction, but
      the underlying mechanism is unknown. APC exerts both antithrombotic and
      cytoprotective properties, the latter via modulation of protease-activated
      receptor-1 (PAR-1) signaling. We generated APC variants to study the relative
      importance of the two functions of APC in a model of LPS-induced renal
      microvascular dysfunction. Compared with wild-type APC, the K193E variant
      exhibited impaired anticoagulant activity but retained the ability to mediate PAR
      1-dependent signaling. In contrast, the L8W variant retained anticoagulant
      activity but lost its ability to modulate PAR-1. By administering wild-type APC
      or these mutants in a rat model of LPS-induced injury, we found that the PAR-1
      agonism, but not the anticoagulant function of APC, reversed LPS-induced systemic
      hypotension. In contrast, both functions of APC played a role in reversing LPS
      induced decreases in renal blood flow and volume, although the effects on PAR-1
      dependent signaling were more potent. Regarding potential mechanisms for these
      findings, APC-mediated PAR-1 agonism suppressed LPS-induced increases in the
      vasoactive peptide adrenomedullin and infiltration of iNOS-positive leukocytes
      into renal tissue. However, the anticoagulant function of APC was responsible for
      suppressing LPS-induced stimulation of the proinflammatory mediators ACE-1, IL-6,
      and IL-18, perhaps accounting for its ability to modulate renal hemodynamics.
      Both variants reduced active caspase-3 and abrogated LPS-induced renal
      dysfunction and pathology. We conclude that although PAR-1 agonism is solely
      responsible for APC-mediated improvement in systemic hemodynamics, both functions
      of APC play distinct roles in attenuating the response to injury in the kidney.

PMID- 19092126
TI  - Proteasomal processing of albumin by renal dendritic cells generates antigenic
      peptides.
AB  - The role of dendritic cells (DC) that accumulate in the renal parenchyma of non
      immune-mediated proteinuric nephropathies is not well understood. Under certain
      circumstances, DC capture immunologically ignored antigens, including self
      antigens, and present them within MHC class I, initiating an autoimmune response.
      We studied whether DC could generate antigenic peptides from the self-protein
      albumin. Exposure of rat proximal tubular cells to autologous albumin resulted in
      its proteolytic cleavage to form an N-terminal 24-amino acid peptide (ALB1-24).
      This peptide was further processed by the DC proteasome into antigenic peptides
      that had binding motifs for MHC class I and were capable of activating syngeneic
      CD8+ T cells. In vivo, the rat five-sixths nephrectomy model allowed the
      localization and activation of renal DC. Accumulation of DC in the renal
      parenchyma peaked 1 wk after surgery and decreased at 4 wk, concomitant with
      their appearance in the renal draining lymph nodes. DC from renal lymph nodes,
      loaded with ALB1-24, activated syngeneic CD8+ T cells in primary culture. The
      response of CD8+ T cells of five-sixths nephrectomized rats was amplified with
      secondary stimulation. In contrast, DC from renal lymph nodes of five-sixths
      nephrectomized rats treated with the proteasomal inhibitor bortezomib lost their
      capacity to stimulate CD8+ T cells in primary and secondary cultures. These data
      suggest that albumin can be a source of potentially antigenic peptides upon renal
      injury and that renal DC play a role in processing self-proteins through a
      proteasome-dependent pathway.

PMID- 19092127
TI  - Dilemmas in the management of atrial fibrillation in chronic kidney disease.
AB  - Patients with chronic kidney disease (CKD) have an increased risk for
      cardiovascular morbidity and mortality. Little attention has been paid to the
      problem of atrial fibrillation, although this arrhythmia is very frequent with a
      prevalence of 13 to 27% in patients on long-term hemodialysis. Because of the
      large number of pathophysiologic mechanisms involved, these patients have a high
      risk for both thromboembolic events and hemorrhagic complications. Stroke is a
      frequent complication in CKD: The US Renal Data System reports an incidence of
      15.1% in hemodialysis patients compared with 9.6% in patients with other stages
      of CKD and 2.6% in a control cohort without CKD. The 2-yr mortality rates after
      stroke in these subgroups were 74, 55, and 28%, respectively. Although oral
      coumadin is the treatment of choice for atrial fibrillation, its use in patients
      with CKD is reported only in limited studies, all in hemodialysis patients, and
      is associated with a markedly increased rate of bleeding compared with patients
      without CKD. With regard to the high risk for stroke and the conflicting data
      about oral anticoagulation, an individualized stratification algorithm is
      presented based on relevant studies.

PMID- 19092128
TI  - Relationship between dialysis modality and mortality.
AB  - Mortality differences between peritoneal dialysis (PD) and hemodialysis (HD) are
      widely debated. In this study, mortality was compared between patients treated
      with PD and HD (including home HD) using data from 27,015 patients in the
      Australia and New Zealand Dialysis and Transplant Registry, 25,287 of whom were
      still receiving PD or HD 90 d after entry into the registry. Overall mortality
      rates were significantly lower during the 90- to 365-d period among those being
      treated with PD at day 90 (adjusted hazard ratio [HR] 0.89; 95% confidence
      interval [CI] 0.81 to 0.99]; P < 0.001). This effect, however, varied in
      direction and size with the presence of comorbidities: Younger patients without
      comorbidities had a mortality advantage with PD treatment, but other groups did
      not. After 12 mo, the use of PD at day 90 was associated with significantly
      increased mortality (adjusted HR 1.33; 95% CI 1.24 to 1.42; P < 0.001). In a
      supplementary as-treated analysis, PD treatment was associated with lower
      mortality during the first 90 d (adjusted HR 0.67; 95% CI 0.56 to 0.81; P <
      0.001). These data suggest that the effect of dialysis modality on survival for
      an individual depends on time, age, and presence of comorbidities. Treatment with
      PD may be advantageous initially but may be associated with higher mortality
      after 12 mo.

PMID- 19092131
TI  - Anti-Candida activity of alpha-melanocyte-stimulating hormone (alpha-MSH)
      peptides.
AB  - Previously, alpha-MSH, a 13-amino acid neuropeptide and the tripeptide alpha-MSH
      have been shown to possess potent antimicrobial properties. We performed
      microplate based growth inhibition assays on C. albicans with alpha-MSH, but
      could not observe any growth inhibiting effect. Repeating the originally
      published assay with different C. albicans strains, we detected a mild growth
      inhibiting effect of 100 microM alpha-MSH, but again no effect of alpha-MSH.

PMID- 19092135
TI  - Carotid plaque stabilization and progression after stroke or TIA.

PMID- 19092133
TI  - Relics of repeat-induced point mutation direct heterochromatin formation in
      Neurospora crassa.
AB  - Both RNAi-dependent and -independent mechanisms have been implicated in the
      establishment of heterochromatin domains, which may be stabilized by feedback
      loops involving chromatin proteins and modifications of histones and DNA.
      Neurospora crassa sports features of heterochromatin found in higher eukaryotes,
      namely cytosine methylation (5mC), methylation of histone H3 lysine 9 (H3K9me),
      and heterochromatin protein 1 (HP1), and is a model to investigate
      heterochromatin establishment and maintenance. We mapped the distribution of HP1,
      5mC, H3K9me3, and H3K4me2 at 100 bp resolution and explored their interplay. HP1,
      H3K9me3, and 5mC were extensively co-localized and defined 44 heterochromatic
      domains on linkage group VII, all relics of repeat-induced point mutation.
      Interestingly, the centromere was found in an approximately 350 kb
      heterochromatic domain with no detectable H3K4me2. 5mC was not found in genes, in
      contrast to the situation in plants and animals. H3K9me3 is required for HP1
      localization and DNA methylation in N. crassa. In contrast, we found that
      localization of H3K9me3 was independent of 5mC or HP1 at virtually all
      heterochromatin regions. In addition, we observed complete restoration of DNA
      methylation patterns after depletion and reintroduction of the H3K9 methylation
      machinery. These data show that A:T-rich RIP'd DNA efficiently directs
      methylation of H3K9, which in turn, directs methylation of associated cytosines.

PMID- 19092137
TI  - Vascular remodeling in diabetes: don't leave without your STAT5.

PMID- 19092136
TI  - Cannabinoid CB1 receptor antagonists for atherosclerosis and cardiometabolic
      disorders: new hopes, old concerns?

PMID- 19092138
TI  - Microarray-based characterization of a colony assay used to investigate
      endothelial progenitor cells and relevance to endothelial function in humans.
AB  - OBJECTIVE: An assay proposed to quantify endothelial progenitor cell (EPC)
      colonies in humans was investigated to determine the phenotype of recovered cells
      and their relevance to in vivo endothelial function. METHODS AND RESULTS: Twelve
      sedentary subjects participating in a worksite wellness program underwent
      endothelial flow-mediated dilation (FMD) testing of the brachial artery and blood
      sampling for EPC colony assay. Microarray-based genotypic characterization of
      colonies showed surface markers consistent with T lymphocyte phenotype, but not
      with an EPC (CD34, CD133, VEGFR-2) or endothelial (CD146) phenotype. Gene
      expression patterns more closely matched T lymphocytes (r=0.87) than endothelial
      cells (r=0.66) in our microarray database. Flow cytometry of colonies confirmed
      large populations of CD3+CD45+ T cells (>75%) and few CD146+CD45- endothelial
      cells (<1%). Further, there was no correlation between colony number and the
      magnitude of FMD (r=-0.1512, P=0.6389). After exercise training, subjects
      improved FMD, from 6.7+/-2.0 to 8.7+/-1.9% (P=0.0043). Colonies also increased
      (P=0.0210), but without relation to FMD (r=0.1074, P=0.7396). T lymphocyte
      phenotype persisted after exercise (r=0.87). CONCLUSIONS: Cells in a commonly
      used EPC colony assay have a gene expression and cell surface marker profile
      consistent with a predominance of T lymphocytes and have an unclear relevance to
      endothelial function, either before or after exercise training.

PMID- 19092139
TI  - The encounter between informal and professional care at the end of life.
AB  - The purpose of this study was to obtain and describe in-depth knowledge about
      family carers' experiences of the encounter, in a hospital, between informal and
      professional care at the end of life. A hermeneutic approach was chosen, and we
      conducted interviews with 27 family carers 6 to 8 months after their loved one's
      death. In the encounter, the family carers made their own assessment of their
      loved one's condition and situation. The professionals' attitudes could both
      promote and impede the interaction between the two forms of care. Family carers'
      care actions were characterized by struggling to get treatment, being left
      behind, being partners, keeping the illness at a distance, hovering beside their
      loved one, waiting for death, and being experts and protectors. The main
      interpretation of the findings is that family carers possess practical knowledge
      about what care is the best, or least harmful, for their loved one. This can be
      linked to what Aristotle called phronesis.

PMID- 19092140
TI  - Dreams of my daughter: an ectopic pregnancy.
AB  - Autoethnographic narrative, personal journal excerpts, and artifacts were
      employed to narrate the story of my ectopic pregnancy and experiences with the
      medical field. The name "Doctor" is invoked as a way of objectifying yet
      protecting the anonymity of the doctor who objectified and did not protect me. A
      methodological discussion of the following tensions in autoethnography is
      presented: intimacy/professionality, art/science, showing/explaining.

PMID- 19092141
TI  - Creating a quality-improvement dialogue: utilizing knowledge from frontline
      staff, managers, and experts to foster health care quality improvement.
AB  - There is a growing consensus that a hybrid of two common approaches to quality
      improvement (QI), local participatory QI and expert QI, might be the best method
      for achieving quality care. Achieving such a hybrid requires that content experts
      establish an ongoing dialogue with both frontline staff members and managers. In
      this study we examined frontline staff members' and managers' preferences
      regarding how to conduct such a dialogue, and we provide practical suggestions
      for implementation. The two groups shared a number of preferences (e.g., verbal
      face-to-face exchanges, discussions focused on quality of care). There were also
      some differences. For example, although managers were interested in discussions
      of business aspects (e.g., costs), frontline staff members were concerned with
      workload issues. Finally, although informants acknowledged that engaging in a QI
      dialogue was time consuming, they also believed it was essential if health care
      organizations are to improve the quality of care they provide.

PMID- 19092142
TI  - Women coping successfully with multiple sclerosis and the precursors of change.
AB  - In this qualitative study, we explored the question of why some women with
      progressive forms of multiple sclerosis (MS) cope successfully in spite of
      disease progression. Ten women with progressive courses of MS, the more
      physically challenging forms of the disease, who self-reported as coping
      successfully with the disease, participated in the study. The study features an
      interview protocol using a psychotherapeutic model of change, precursors of
      change model, and incorporates a then-post design. The women's rich descriptions
      and explanations of precursors indicate the differences between the precursors
      used most frequently at time of diagnosis with MS and at the time of interview.
      The article provides a glimpse into the experiences these women have had with the
      continued change and unpredictability that the disease often engenders.

PMID- 19092143
TI  - Rifaximin for treatment of hepatic encephalopathy.
AB  - OBJECTIVE: To review the effectiveness and safety of rifaximin in the treatment
      of hepatic encephalopathy (HE). DATA SOURCES: MEDLINE (1990-October 2008) was
      searched using the terms rifaximin, rifamycins, hepatic encephalopathy, liver
      cirrhosis, and acute liver failure. Other sources included the bibliographies of
      pertinent articles as well as programs and abstracts from infectious diseases and
      gastrointestinal diseases meetings. STUDY SELECTION AND DATA EXTRACTION: All
      English-language articles identified from the search were evaluated. All primary
      literature that addressed the efficacy and safety of rifaximin in the treatment
      of HE was included in this review. DATA SYNTHESIS: HE is a complex
      neuropsychiatric syndrome seen in patients with liver failure. It is
      characterized by disturbances in consciousness and behavior, personality changes,
      fluctuating neurologic signs, asterixis, and electroencephalographic changes.
      Although the etiology of HE is unknown, the accumulation of several gut-derived
      toxins such as mercaptans, ammonia, and benzodiazepine has been implicated.
      Current treatment options for HE include agents that reduce the concentration of
      these toxins, such as nonabsorbable disaccharides and antibiotics. Several
      studies have evaluated the use of rifaximin in the treatment of HE. They include
      a dose-finding study, 9 open-label studies, and 4 double-blind studies comparing
      rifaximin with either nonabsorbable disaccharides or antibiotics. Commonly used
      outcomes in most of these studies were changes in portal systemic encephalopathy
      index and the improvement in HE grade. Despite various limitations of the
      studies, rifaximin showed superior efficacy compared with lactulose for the
      treatment of HE, similar efficacy to paromomycin, and similar or greater efficacy
      than neomycin. Rifaximin was found to be associated with fewer hospitalizations,
      fewer days of hospitalization, and lower hospitalization charges than were seen
      with lactulose. Rifaximin also had a better tolerance profile than the
      comparative agents. CONCLUSIONS: Rifaximin appears to be an effective and safe
      treatment option for HE. Better-designed studies are needed to characterize its
      efficacy in the treatment of HE.

PMID- 19092144
TI  - Do medication samples jeopardize patient safety?
AB  - BACKGROUND: Medication samples are commonly dispensed by prescribers. Written
      consumer medication information (CMI) provided with sample packaging is an
      important source of patient information. Although one-third of Americans have
      health literacy deficiencies, previous studies have found that CMI is often too
      complex for many patients to understand. This may prevent patients from using
      these medications appropriately. OBJECTIVE: To evaluate readability and
      formatting characteristics of CMI included with nonsolid (ie, topical
      cream/lotion, inhalation, transdermal) drug samples. METHODS: We collected a
      convenience sample of nonsolid dosage sample medications (N = 55) from several
      different private and university-affiliated primary care and specialty physician
      practices at a large academic medical center in the southeastern US. We noted
      whether CMI was present and, if it was, we assessed it for instruction
      presentation, reading level, text size, format/layout, and comprehensibility.
      RESULTS: Most (43 of 55) products included CMI, either as a separate leaflet or
      directly on the packaging. Reading level of CMI leaflets ranged from the 6th- to
      14th-grade level, with just 4 (16.0%) written at the recommended 6th-grade level.
      Text font point size was 9.48 +/- 2.14 (mean +/- SD; range 5-12). Text printed
      directly on sample packaging averaged 6.61 point +/- 2.62 (4-11) font size.
      Ninety-two percent of CMI leaflets included a combination of text and pictures;
      only 11.1% of CMI printed directly on the packaging used pictorial aids.
      CONCLUSIONS: Most CMI accompanying nonsolid medication samples is written at a
      reading level that exceeds that of many consumers and does not meet recommended
      standards for readability and comprehensibility of patient education material.

PMID- 19092146
TI  - Modulation of blood pressure by central melanocortinergic pathways.
AB  - BACKGROUND: Weight gain and weight loss are associated with changes in blood
      pressure through unknown mechanisms. Central melanocortinergic signaling is
      implicated in the control of energy balance and blood pressure in rodents, but
      there is no information regarding such an association with blood pressure in
      humans. METHODS: We assessed blood pressure, heart rate, and urinary
      catecholamines in overweight or obese subjects with a loss-of-function mutation
      in MC4R, the gene encoding the melanocortin 4 receptor, and in equally overweight
      control subjects. We also examined the effects of an MC4R agonist administered
      for 7 days in 28 overweight or obese volunteers. RESULTS: The prevalence of
      hypertension was markedly lower in the MC4R-deficient subjects than in the
      control subjects (24% vs. 53%, P=0.009). After the exclusion of subjects taking
      antihypertensive medications, blood-pressure levels were significantly lower in
      MC4R-deficient subjects than in control subjects, with mean (+/-SE) systolic
      blood pressures of 123+/-14 mm Hg and 131+/-12 mm Hg, respectively (P=0.02), and
      mean diastolic blood pressures of 73+/-10 mm Hg and 79+/-7 mm Hg, respectively
      (P=0.03). As compared with control subjects, MC4R-deficient subjects had a lower
      increase in heart rate on waking (P=0.007), a lower heart rate during euglycemic
      hyperinsulinemia (P<0.001), and lower 24-hour urinary norepinephrine excretion
      (P=0.04). The maximum tolerated daily dose of 1.0 mg of the MC4R agonist led to
      significant increases of 9.3+/-1.9 mm Hg in systolic blood pressure and of 6.6+/
      1.1 mm Hg in diastolic blood pressure (P<0.001 for both comparisons) at 24 hours,
      as compared with placebo. Differences in blood pressure were not explained by
      changes in insulin levels; there were no significant adverse events. CONCLUSIONS:
      Results of our genetic and pharmacologic studies implicate melanocortinergic
      signaling in the control of human blood pressure through an insulin-independent
      mechanism.

PMID- 19092147
TI  - Images in clinical medicine. Subungual exostosis.

PMID- 19092148
TI  - Medical student debt--is there a limit?

PMID- 19092149
TI  - The future of primary care--the community responds.

PMID- 19092145
TI  - Glucose control and vascular complications in veterans with type 2 diabetes.
AB  - BACKGROUND: The effects of intensive glucose control on cardiovascular events in
      patients with long-standing type 2 diabetes mellitus remain uncertain. METHODS:
      We randomly assigned 1791 military veterans (mean age, 60.4 years) who had a
      suboptimal response to therapy for type 2 diabetes to receive either intensive or
      standard glucose control. Other cardiovascular risk factors were treated
      uniformly. The mean number of years since the diagnosis of diabetes was 11.5, and
      40% of the patients had already had a cardiovascular event. The goal in the
      intensive-therapy group was an absolute reduction of 1.5 percentage points in the
      glycated hemoglobin level, as compared with the standard-therapy group. The
      primary outcome was the time from randomization to the first occurrence of a
      major cardiovascular event, a composite of myocardial infarction, stroke, death
      from cardiovascular causes, congestive heart failure, surgery for vascular
      disease, inoperable coronary disease, and amputation for ischemic gangrene.
      RESULTS: The median follow-up was 5.6 years. Median glycated hemoglobin levels
      were 8.4% in the standard-therapy group and 6.9% in the intensive-therapy group.
      The primary outcome occurred in 264 patients in the standard-therapy group and
      235 patients in the intensive-therapy group (hazard ratio in the intensive
      therapy group, 0.88; 95% confidence interval [CI], 0.74 to 1.05; P=0.14). There
      was no significant difference between the two groups in any component of the
      primary outcome or in the rate of death from any cause (hazard ratio, 1.07; 95%
      CI, 0.81 to 1.42; P=0.62). No differences between the two groups were observed
      for microvascular complications. The rates of adverse events, predominantly
      hypoglycemia, were 17.6% in the standard-therapy group and 24.1% in the intensive
      therapy group. CONCLUSIONS: Intensive glucose control in patients with poorly
      controlled type 2 diabetes had no significant effect on the rates of major
      cardiovascular events, death, or microvascular complications with the exception
      of progression of albuminuria (P = 0.01) [added]. (ClinicalTrials.gov number,
      NCT00032487.)

PMID- 19092150
TI  - Dicer, Drosha, and outcomes in patients with ovarian cancer.
AB  - BACKGROUND: We studied Dicer and Drosha, components of the RNA-interference
      machinery, in ovarian cancer. METHODS: We measured messenger RNA (mRNA) levels of
      Dicer and Drosha in specimens of invasive epithelial ovarian cancer from 111
      patients, using a quantitative reverse-transcriptase-polymerase-chain-reaction
      assay, and compared the results with clinical outcomes. Validation was performed
      with the use of published microarray data from cohorts of patients with ovarian,
      breast, and lung cancer. Mutational analyses of genomic DNA from the Dicer and
      Drosha genes were performed in a subgroup of ovarian-cancer specimens. Dicer
      dependent functional assays were performed by means of in vitro transfection with
      small interfering RNA (siRNA) and short hairpin RNA (shRNA). RESULTS: Levels of
      Dicer and Drosha mRNA correlated with the levels of expression of the
      corresponding protein and were decreased in 60% and 51% of ovarian-cancer
      specimens, respectively. Low Dicer expression was significantly associated with
      advanced tumor stage (P=0.007), and low Drosha expression with suboptimal
      surgical cytoreduction (P=0.02). Cancer specimens with both high Dicer expression
      and high Drosha expression were associated with increased median survival (>11
      years, vs. 2.66 years for other subgroups; P<0.001). We found three independent
      predictors of reduced disease-specific survival in multivariate analyses: low
      Dicer expression (hazard ratio, 2.10; P=0.02), high-grade histologic features
      (hazard ratio, 2.46; P=0.03), and poor response to chemotherapy (hazard ratio,
      3.95; P<0.001). Poor clinical outcomes among patients with low Dicer expression
      were validated in additional cohorts of patients. Rare missense mutations were
      found in the Dicer and Drosha genes, but their presence or absence did not
      correlate with the level of expression. Functional assays indicated that gene
      silencing with shRNA, but not siRNA, may be impaired in cells with low Dicer
      expression. CONCLUSIONS: Our findings indicate that levels of Dicer and Drosha
      mRNA in ovarian-cancer cells have associations with outcomes in patients with
      ovarian cancer.

PMID- 19092153
TI  - PHD2 mutation and congenital erythrocytosis with paraganglioma.
AB  - Prolyl hydroxylase domain (PHD) proteins play a major role in regulating the
      hypoxia-inducible factor (HIF) that induces expression of genes involved in
      angiogenesis, erythropoiesis, and cell metabolism, proliferation, and survival.
      Germ-line mutations in the prolyl hydroxylase domain 2 gene (PHD2) have been
      reported in patients with familial erythrocytosis but not in association with
      tumors. We describe a patient with erythrocytosis and recurrent paraganglioma who
      carries a newly discovered PHD2 mutation. This mutation affects PHD2 function and
      stabilizes HIF-alpha proteins. In addition, we demonstrate loss of heterozygosity
      of PHD2 in the tumor, suggesting that PHD2 could be a tumor-suppressor gene.

PMID- 19092154
TI  - Temporomandibular disorders.

PMID- 19092151
TI  - Thrombolysis during resuscitation for out-of-hospital cardiac arrest.
AB  - BACKGROUND: Approximately 70% of persons who have an out-of-hospital cardiac
      arrest have underlying acute myocardial infarction or pulmonary embolism.
      Therefore, thrombolysis during cardiopulmonary resuscitation may improve
      survival. METHODS: In a double-blind, multicenter trial, we randomly assigned
      adult patients with witnessed out-of-hospital cardiac arrest to receive
      tenecteplase or placebo during cardiopulmonary resuscitation. Adjunctive heparin
      or aspirin was not used. The primary end point was 30-day survival; the secondary
      end points were hospital admission, return of spontaneous circulation, 24-hour
      survival, survival to hospital discharge, and neurologic outcome. RESULTS: After
      blinded review of data from the first 443 patients, the data and safety
      monitoring board recommended discontinuation of enrollment of asystolic patients
      because of low survival, and the protocol was amended. Subsequently, the trial
      was terminated prematurely for futility after enrolling a total of 1050 patients.
      Tenecteplase was administered to 525 patients and placebo to 525 patients; the
      two treatment groups had similar clinical profiles. We did not detect any
      significant differences between tenecteplase and placebo in the primary end point
      of 30-day survival (14.7% vs. 17.0%; P=0.36; relative risk, 0.87; 95% confidence
      interval, 0.65 to 1.15) or in the secondary end points of hospital admission
      (53.5% vs. 55.0%, P=0.67), return of spontaneous circulation (55.0% vs. 54.6%,
      P=0.96), 24-hour survival (30.6% vs. 33.3%, P=0.39), survival to hospital
      discharge (15.1% vs. 17.5%, P=0.33), or neurologic outcome (P=0.69). There were
      more intracranial hemorrhages in the tenecteplase group. CONCLUSIONS: When
      tenecteplase was used without adjunctive antithrombotic therapy during advanced
      life support for out-of-hospital cardiac arrest, we did not detect an improvement
      in outcome, in comparison with placebo. (ClinicalTrials.gov number, NCT00157261.)

PMID- 19092152
TI  - Alfuzosin and symptoms of chronic prostatitis-chronic pelvic pain syndrome.
AB  - BACKGROUND: In men with chronic prostatitis-chronic pelvic pain syndrome,
      treatment with alpha-adrenergic receptor blockers early in the course of the
      disorder has been reported to be effective in some, but not all, relatively small
      randomized trials. METHODS: We conducted a multicenter, randomized, double-blind,
      placebo-controlled trial to evaluate the efficacy of alfuzosin, an alpha
      adrenergic receptor blocker, in reducing symptoms in men with chronic prostatitis
      chronic pelvic pain syndrome. Participation in the study required diagnosis of
      the condition within the preceding 2 years and no previous treatment with an
      alpha-adrenergic receptor blocker. Men were randomly assigned to treatment for 12
      weeks with either 10 mg of alfuzosin per day or placebo. The primary outcome was
      a reduction of at least 4 points (from baseline to 12 weeks) in the score on the
      National Institutes of Health Chronic Prostatitis Symptom Index (NIH-CPSI)
      (range, 0 to 43; higher scores indicate more severe symptoms). A 4-point decrease
      is the minimal clinically significant difference in the score. RESULTS: A total
      of 272 eligible participants underwent randomization, and in both study groups,
      49.3% of participants had a decrease of at least 4 points in their total NIH-CPSI
      score (rate difference associated with alfuzosin, 0.1%; 95% confidence interval, 
      11.2 to 11.0; P=0.99). In addition, a global response assessment showed similar
      response rates at 12 weeks: 33.6% in the placebo group and 34.8% in the alfuzosin
      group (P=0.90). The rates of adverse events in the two groups were also similar.
      CONCLUSIONS: Our findings do not support the use of alfuzosin to reduce the
      symptoms of chronic prostatitis-chronic pelvic pain syndrome in men who have not
      received prior treatment with an alpha-blocker. (ClinicalTrials.gov number,
      NCT00103402.)

PMID- 19092155
TI  - Images in clinical medicine. Postpartum venous thromboembolism.

PMID- 19092156
TI  - Case records of the Massachusetts General Hospital. Case 39-2008. A 51-year-old
      woman with splenomegaly and anemia.

PMID- 19092157
TI  - MicroRNA in cancer prognosis.

PMID- 19092158
TI  - Boosting beta-cell numbers.

PMID- 19092159
TI  - Cetuximab in head and neck cancer.

PMID- 19092160
TI  - Platelets and the vascular wall.

PMID- 19092161
TI  - Motesanib diphosphate in progressive differentiated thyroid cancer.

PMID- 19092162
TI  - Military medical ethics.

PMID- 19092163
TI  - Amyloid and transplanted islets.

PMID- 19092164
TI  - Small-cell lung cancer and necrolytic migratory erythema.

PMID- 19092165
TI  - Protection from clinical peripheral sensory neuropathy in Alstrom syndrome in
      contrast to early-onset type 2 diabetes.
AB  - OBJECTIVE: Alstrom syndrome, with type 2 diabetes, and blindness could confer a
      high risk of foot ulceration. Clinical testing for neuropathy in Alstrom syndrome
      and matched young-onset type 2 diabetic subjects was therefore undertaken.
      RESEARCH DESIGN AND METHODS: Fifty-eight subjects with Alstrom syndrome (18
      insulin-resistant nondiabetic and 40 diabetic; aged 8-43 years) and 30 young
      onset diabetic subjects (aged 13-35 years) were studied. Neuropathy symptom
      questionnaires were administered. Graded monofilament and 128-MHz tuning fork
      vibration perception were assessed in both feet. RESULTS: Neuropathic symptoms,
      loss of monofilament, and/or vibration perception were reported by 12 of the 30
      young-onset type 2 diabetic subjects (6 had neuropathic ulceration) but none of
      the subjects with Alstrom syndrome. CONCLUSIONS: The striking preservation of
      protective foot sensation in Alstrom syndrome may provide a clue to the causes of
      differential susceptibility to neuropathy in the wider diabetic population.

PMID- 19092166
TI  - Interleukin-18 is a strong predictor of cardiovascular events in elderly men with
      the metabolic syndrome: synergistic effect of inflammation and hyperglycemia.
AB  - OBJECTIVE: The aim of this study was to investigate the role of inflammatory
      markers as potential predictors of cardiovascular events in subjects with and
      without the metabolic syndrome. RESEARCH DESIGN AND METHODS: This was a post hoc
      analysis from the Diet and Omega-3 Intervention Trial (DOIT), comprising 563
      elderly men with (n = 221) and without (n = 342) metabolic syndrome. Circulating
      inflammatory markers were measured. RESULTS: During 3 years, 68 cardiovascular
      events were recorded. In the total population, C-reactive protein (CRP) (P <
      0.001), interleukin-18 (IL-18) (P = 0.008), and IL-6 (P = 0.003) were elevated in
      subjects with events. In subjects with metabolic syndrome, IL-18 was the
      strongest predictor (adjusted odds ratio 2.9 [95% CI 1.1-7.8]). In subjects
      without metabolic syndrome, only CRP seemed to be an independent predictor (3.3
      [1.5-7.3]). There was a significant interaction between fasting glucose and IL-18
      (P = 0.008) and IL-6 (P = 0.024) but not CRP. Elevated fasting glucose (>6.2
      mmol/l) markedly increased the predictive power of inflammatory markers (IL-18:
      5.5 [1.4-21.1], IL-6: 3.5 [1.0-11.8], and CRP: 3.5 [1.0-11.9]). For IL-18, there
      was a stepwise increase in event rate by quartiles of fasting glucose.
      CONCLUSIONS: IL-18 was an independent predictor of cardiovascular events in
      subjects with metabolic syndrome and even more so in the presence of elevated
      fasting glucose. Our findings suggest a mutually potentiating effect of
      hyperglycemia and inflammation in cardiovascular risk prediction.

PMID- 19092167
TI  - Lipid and lipoprotein profiles in youth with and without type 1 diabetes: the
      SEARCH for Diabetes in Youth case-control study.
AB  - OBJECTIVE: The purpose of this study was to compare the lipid profile and the
      prevalence of lipid abnormalities in youth with and without type 1 diabetes and
      explore the role of glycemic control on the hypothesized altered lipid profile in
      youth with type 1 diabetes. RESEARCH DESIGN AND METHODS: We conducted a cross
      sectional analysis of 512 youth with type 1 diabetes (mean duration 4.22 years)
      and 188 healthy control subjects aged 10-22 years in Colorado and South Carolina.
      SEARCH for Diabetes in Youth (SEARCH) participants with type 1 diabetes and
      healthy control subjects recruited from primary care offices in the same
      geographic regions were invited to attend a research visit. Fasting lipid
      profiles were compared between youth with type 1 diabetes (stratified according
      to categories of optimal [A1C <7.5%] and suboptimal [A1C >or=7.5%] glycemic
      control) and healthy nondiabetic youth, using multiple linear and logistic
      regression. RESULTS: Youth with type 1 diabetes and optimal A1C had lipid
      concentrations that were similar (total cholesterol, LDL cholesterol, and LDL
      particle size) or even less atherogenic (HDL cholesterol, non-HDL cholesterol,
      triglyceride, and triglyceride-to-HDL cholesterol ratio) than those observed in
      nondiabetic youth, whereas youth with suboptimal glycemic control had elevated
      standard lipid levels (total cholesterol, LDL cholesterol, and non-HDL
      cholesterol). Youth with type 1 diabetes also had significantly elevated
      apolipoprotein B levels and more small, dense LDL particles than nondiabetic
      youth, regardless of glycemic control. CONCLUSIONS: Youth with type 1 diabetes
      have abnormal lipid levels and atherogenic changes in lipoprotein composition,
      even after a relatively short disease duration. As in adults, glycemic control is
      an important mediator of these abnormalities.

PMID- 19092168
TI  - Intensive glycemic control and the prevention of cardiovascular events:
      implications of the ACCORD, ADVANCE, and VA diabetes trials: a position statement
      of the American Diabetes Association and a scientific statement of the American
      College of Cardiology Foundation and the American Heart Association.

PMID- 19092170
TI  - Retinal microvascular caliber and chronic kidney disease in an Asian population.
AB  - Retinal arteriolar narrowing is a marker of microvascular damage from elevated
      blood pressure. Between August 2004 and June 2006, the authors examined the
      association between retinal vascular diameter and chronic kidney disease in a
      population-based cohort of 3,280 community-dwelling adults of Malay ethnicity
      aged 40-80 years living in Singapore. Chronic kidney disease was defined as 1) an
      estimated glomerular filtration rate (eGFR) of <60 mL/minute/1.73 m(2) from serum
      creatinine or 2) the presence of micro/macroalbuminuria defined as urinary
      albumin:creatinine ratios of > or = 17 mg/g for men and > or = 25 mg/g for women.
      Retinal arteriolar and venular diameters were measured and summarized as central
      retinal arteriolar equivalent (CRAE) and central retinal venular equivalent
      (CRVE). Individuals with reduced CRAE were more likely to have chronic kidney
      disease than those with increased CRAE. After controlling for age, gender,
      education, smoking, diabetes, hypertension, body mass index, and total and high
      density lipoprotein cholesterol, the authors found the odds ratio comparing the
      smallest with the largest CRAE quartile to be 1.42 (95% confidence interval:
      1.03, 1.96; P(trend) = 0.02) for eGFR of <60 mL/minute/1.73 m(2) and 1.80 (95%
      confidence interval: 1.11, 2.91; P(trend) = 0.01) for micro/macroalbuminuria.
      Retinopathy was also found to be positively associated with both eGFR and
      micro/macroalbuminuria. Retinal venular diameter was not associated with chronic
      kidney disease. These data suggest that retinal arteriolar narrowing is
      associated with chronic kidney disease, independent of diabetes and hypertension.

PMID- 19092169
TI  - Serum monocyte chemoattractant protein-1 concentrations associate with diabetes
      status but not arterial stiffness in children with type 1 diabetes.
AB  - OBJECTIVE: The relationship between circulating markers of inflammation and
      arterial stiffness in children with type 1 diabetes is not well studied. We
      tested whether inflammatory monocyte chemoattractant protein (MCP)-1
      concentrations correlate with arterial stiffness or type 1 diabetes status.
      RESEARCH DESIGN AND METHODS: MCP-1 concentrations and radial tonometry data were
      available for 98 children with type 1 diabetes and 55 healthy control subjects.
      Arterial stiffness was calculated as augmentation index corrected for a heart
      rate of 75 (AI75). Correlation between MCP-1 and AI75 and differences in MCP-1
      concentrations between case and control subjects were tested. RESULTS: MCP-1 was
      significantly higher in children with type 1 diabetes than in control subjects (P
      < 0.001). However, there were no correlations between MCP-1 and AI75 in the
      overall sample or upon stratification by type 1 diabetes status (range P = 0.28
      0.66). CONCLUSIONS: Circulating MCP-1 was not associated with arterial stiffness
      but was significantly elevated in children with type 1 diabetes, indicating a
      proinflammatory state in children as young as 10 years. The clinical significance
      of MCP-1 elevation in type 1 diabetes needs further investigation.

PMID- 19092171
TI  - Detection and characterization of ultra-thin films with neutron reflectometry.
AB  - Specular reflectometry, being a technique based on interference between coherent
      X-ray or neutron beams, is considered to have a fundamental limit in sensing the
      presence of films that are too thin for the maximum momentum transfer, Q(max), to
      which reflectivity has been measured. However, it is known both experimentally
      and from simulations that an ultra-thin film, with thickness t << 2pi/Q(max), can
      be detected if it exists sandwiched between two contrast-matched media. This
      possibility is qualitatively explained using phase-vector diagrams. The diagrams
      also show that the detection is through unmistakable shifts of the interference
      maxima and minima, and that the scattering-length density of the ultra-thin film
      determined by least-squares analysis is unique.

PMID- 19092172
TI  - Computation and parametrization of the temperature dependence of Debye-Waller
      factors for group IV, III-V and II-VI semiconductors.
AB  - We calculated the temperature dependence of the Debye-Waller factors for a
      variety of group IV, III-V and II-VI semiconductors from 0.1 to 1000 K. The
      approach used to fit the temperature dependence is described and resulting fit
      parameters are tabulated for each material. The Debye-Waller factors are deduced
      from generalized phonon densities of states which were derived from first
      principles using the WIEN2k and the ABINIT codes.

PMID- 19092173
TI  - Abelianization of space groups.
AB  - The abelianization of a group is its commutator quotient group. In this paper, we
      provide tables of the abelianizations of all the n-dimensional space groups for n
      = 1, 2, 3. We prove that the exponent of the torsion subgroup of the
      abelianization of an arbitrary n-dimensional space group Gamma divides the order
      of the point group of Gamma.

PMID- 19092174
TI  - Two-wavelength inversion of multiply scattered soft X-ray intensities to charge
      density.
AB  - A method is described for reconstructing the two-dimensional real-space charge
      density of an isolated object from measurement of the soft X-ray transmission
      diffraction pattern when it is affected by strong multiple scattering. The Bloch
      wave scattering-matrix approach is used to show that the diffracted amplitude
      depends only on a simple product of X-ray wavelength and sample thickness (unlike
      the case of relativistic electron diffraction) under reasonable approximations.
      The multislice formulation then gives the effect of a small change in wavelength,
      which involves only single scattering. Dynamical diffraction patterns are
      recorded at two adjacent wavelengths, phased by iterative methods, transformed to
      real space and divided to give a single-scattering wavefunction. This can then be
      used to produce a charge-density map. The extension of the method to tomography
      is discussed. Consideration is first also given to the possibility that
      absorption due to the photoelectric effect may be so severe for soft X-rays that
      multiple elastic scattering becomes so much less probable than photoelectric
      absorption that it may be neglected entirely. A discussion of signs in soft X
      ray, positron and electron multiple-scattering theory is given.

PMID- 19092175
TI  - Dynamic Newton-gradient-direction-type algorithm for multilayer structure
      determination using grazing X-ray specular scattering: numerical simulation and
      analysis.
AB  - A new dynamic iterative algorithm code for retrieving macroscopic multilayer
      structure parameters (the layer thickness and complex refraction index for each
      layer, the surface roughness and the interface roughness between the layers) from
      specular scattering angular scan data is proposed. The use of conventional direct
      methods, particularly the well known Newton algorithm and gradient-direction-type
      algorithm operating dynamically to minimize the error functional in a least
      squares fashion, is explored. Such an approach works well and seems to be
      effective in solving the inverse problem in the high-resolution X-ray
      reflectometry (HRXR) method. In order to demonstrate some features of the
      proposed iterative algorithm, numerical calculations for retrieving three-layer
      structure parameters are carried out using simulated HRXR angular scan data. The
      calculations indicate clearly that the dynamic iterative algorithm is convergent
      and capable of yielding the true solution. It is important that the performance
      coefficient for successful iterative cycles for the absolute minimization of the
      HRXR error functional is quite high even if the initial values of the search
      parameters are chosen rather far from the true values. It is particularly
      noteworthy that the relative number of successful iterative cycles is of the
      order of 90-40% when only moderately accurate initial parameter values, varying
      by +/-10-40% from the true values, are presumed.

PMID- 19092176
TI  - On the determination of fiber tilt angles in fiber diffraction.
AB  - The common digital method that is used to eliminate the effect of fiber tilt from
      fiber diffraction patterns is based on an approximation given by Franklin &
      Gosling [Acta Cryst. (1953), 6, 678-685]. The estimate of the tilt angle is
      iteratively optimized in the so-called ;Fraser correction'. Building on the
      fundamental work of Polanyi [Z. Phys. (1921), 7, 149-180], the exact solution is
      presented.

PMID- 19092177
TI  - Deconvolution of the interatomic vector set using a convolution table.
AB  - The deconvolution of the interatomic vector set (the ideal Patterson function)
      with the superposition technique is not complete because of the vector overlaps:
      multiple images and false peaks usually exist in the superposition map. Here, a
      new method for the deconvolution of the interatomic vector set is presented. This
      method involves constructing a table termed the ;convolution table' from vectors
      in a superposition map and then sorting the table so that vectors belonging to
      different images are separated, and thus the overlaps are naturally solved. This
      method does not use the symmetry information.

PMID- 19092181
TI  - Runoff pollution impacts of polycyclic aromatic hydrocarbons in street dusts from
      a stream network town.
AB  - Runoff with contaminated street dusts has an environmental risk to the aquatic
      environment. An assessment of the diffuse pollution of polycyclic aromatic
      hydrocarbons (PAHs) from a small town and their risks to the township stream
      network was conducted at Yangtze River delta. This assessment is based on
      measurements of 16 PAHs from the US EPA priority list by GC-MS in stream water
      during rainy and dry season, street dusts with different particle sizes, river
      sediments and suspended solids of urban runoff. The maximum level of PAHs in the
      stream water (2,323-4,948 ng L(-1)) were found during rainy season, while
      significantly lower PAHs concentrations (242-998 ng L(-1)) were measured during
      dry season. The total PAHs ranged from 1,629 to 8,986 microg kg(-1) in the street
      dusts. Approximately 55% of the total PAHs were associated with street dust
      particles of diameters less than 250 microm and these accounted for 40% of the
      total. The town reaches sediments were rich in PAHs and it was suggested as the
      sink of street dusts. The research findings suggested that size of street dusts,
      the topographical and hydrological features of the landscape in the stream
      network were the important factors influencing PAH emitted to the receiving
      water. The contribution of urban surface runoff could significantly influence
      PAHs concentration in the stream water. To reduce the pollution of street dust
      into the stream network, the buffer zone along the hydrological pathway is
      suggested and the existing street cleaning methods should also be improved.

PMID- 19092182
TI  - Inhomogeneous feed gas processing in industrial ozone generation.
AB  - The synthesis of ozone by means of dielectric barrier discharge (DBD) is
      extensively used in industry. Ozone generators available on the market differ in
      ozone production capacities, electrode arrangements and working parameters, but
      operate with a uniformly distributed filamentary discharge plasma pattern.In the
      presented work the benefits of inhomogeneous feed gas processing are explored.
      Causality between power induction, production efficiency and working parameters
      are investigated. Different electrode arrangements, evenly distributed within a
      given space parameter, were designed, simulated, manufactured and tested on a
      representative scale. A finite element model was utilized to simulate an
      inhomogeneous power induction pattern along the ozone generator tube. The
      simulation yielded the local power density, the local gas temperature gradient
      and the relative DBD packing density.Results show that the degree of
      filamentation turns out to be decisive, indicating a new potential by means of
      plasma tailoring. An arrangement with a pronounced power induction at the inlet
      of the ozone generator revealed several advantages over homogeneous plasma
      processing arrangements, for which an increase in robustness and a reduction in
      electrical power consumption are achieved.

PMID- 19092183
TI  - A probabilistic cellular automaton for two dimensional contaminant transport
      simulation in ground water.
AB  - In recent years evolutionary computing algorithms have been proposed to solve
      many engineering problems. Genetic algorithms, Neural Networks, and Cellular
      Automata are the branches of evolutionary computing techniques. In this study, it
      is proposed to simulate the contaminant transport in porous media using a
      Cellular Automaton. The physical processes and chemical reactions occurring in
      the ground water system are intricately connected at various scales of space,
      time, transport coefficients and molecular concentration. The validity of
      continuous approach for the simulation of chemical systems with low concentration
      of species and intracellular environments has become subtle. Due to the
      difference in scales of various processes that occur in the ground water system,
      the description of the system can be well defined in the intermediate scale
      called mesoscopic scale, which is in between microscopic and macroscopic
      description. Mesoscopic models provide the relationship between various
      parameters and their evolvement in time, thus establishing the contact between
      modeling at various scales at the interface. In this paper, a Probabilistic
      Cellular Automaton (PCA) model has been developed based on the transport and
      reaction probability values. The developed model was verified and validated for
      one, two dimensional transport systems and also for the simulation of BTEX
      transport in two dimensional system in ground water.

PMID- 19092184
TI  - Climate change mitigation for agriculture: water quality benefits and costs.
AB  - New Zealand is unique in that half of its national greenhouse gas (GHG) inventory
      derives from agriculture--predominantly as methane (CH4) and nitrous oxide (N2O),
      in a 2:1 ratio. The remaining GHG emissions predominantly comprise carbon dioxide
      (CO2) deriving from energy and industry sources. Proposed strategies to mitigate
      emissions of CH4 and N2O from pastoral agriculture in New Zealand are: (1)
      utilising extensive and riparian afforestation of pasture to achieve CO2 uptake
      (carbon sequestration); (2) management of nitrogen through budgeting and/or the
      use of nitrification inhibitors, and minimizing soil anoxia to reduce N2O
      emissions; and (3) utilisation of alternative waste treatment technologies to
      minimise emissions of CH4. These mitigation measures have associated co-benefits
      and co-costs (disadvantages) for rivers, streams and lakes because they affect
      land use, runoff loads, and receiving water and habitat quality. Extensive
      afforestation results in lower specific yields (exports) of nitrogen (N),
      phosphorus (P), suspended sediment (SS) and faecal matter and also has benefits
      for stream habitat quality by improving stream temperature, dissolved oxygen and
      pH regimes through greater shading, and the supply of woody debris and
      terrestrial food resources. Riparian afforestation does not achieve the same
      reductions in exports as extensive afforestation but can achieve reductions in
      concentrations of N, P, SS and faecal organisms. Extensive afforestation of
      pasture leads to reduced water yields and stream flows. Both afforestation
      measures produce intermittent disturbances to waterways during forestry
      operations (logging and thinning), resulting in sediment release from channel re
      stabilisation and localised flooding, including formation of debris dams at
      culverts. Soil and fertiliser management benefits aquatic ecosystems by reducing
      N exports but the use of nitrification inhibitors, viz. dicyandiamide (DCD), to
      achieve this may under some circumstances impair wetland function to intercept
      and remove nitrate from drainage water, or even add to the overall N loading to
      waterways. DCD is water soluble and degrades rapidly in warm soil conditions. The
      recommended application rate of 10 kg DCD/ha corresponds to 6 kg N/ha and may be
      exceeded in warm climates. Of the N2O produced by agricultural systems,
      approximately 30% is emitted from indirect sources, which are waterways draining
      agriculture. It is important therefore to focus strategies for managing N inputs
      to agricultural systems generally to reduce inputs to wetlands and streams where
      these might be reduced to N2O. Waste management options include utilizing the CH4
      resource produced in farm waste treatment ponds as a source of energy, with
      conversion to CO2 via combustion achieving a 21-fold reduction in GHG emissions.
      Both of these have co-benefits for waterways as a result of reduced loadings. A
      conceptual model derived showing the linkages between key land management
      practices for greenhouse gas mitigation and key waterway values and ecosystem
      attributes is derived to aid resource managers making decisions affecting
      waterways and atmospheric GHG emissions.

PMID- 19092185
TI  - MARAPUR--a new process combination for the optimization of MBR.
AB  - The MARAPUR concept is a biological wastewater treatment process based on the MBR
      functional principle. The ultrafiltration of activated sludge takes place in
      pressure-driven hollow fiber membranes. The vertical membrane modules are
      installed compactly in a MEGAMODUL. The permeate extraction is accomplished in
      the cross-flow, which is supported by rinsing aeration. The main process
      advantages are high filtration performance, excellent operation reliability
      provided by wastewater fine sieving and reduced cleaning chemicals demand.
      Wastewater fine sieving with a mesh size of 0.25 mm is an effective measure
      against membrane clogging by hair and fibers.

PMID- 19092186
TI  - Estimation of the impact of particulate organic matter drained from a freshwater
      reservoir on the sea using diatom tracking.
AB  - We estimated the extent of suspended solids (SS) and particulate organic matter
      (POM) discharged from a freshwater reservoir, called the Isahaya Reservoir, into
      a sea area by tracking the diatom frustules produced in the reservoir. The
      estimation method is based on the fact that Skeletonema subsalsum and S.
      costatum, are the predominant diatoms in the reservoir and the sea, respectively,
      and the discharged SS and POM contain the freshwater diatom, S. subsalsum, and
      that the diatom frustules remain undecomposed in the environment even after the
      plankton decays. The results of the sediment trap experiment and bottom sediment
      survey showed that the distribution of diatom frustules in the bottom sediment
      had good agreement with that in the water column in the sea, and the greatest
      amounts of the drained SS and POM were estimated to have reached and settled down
      on the bottom sediment in the sea area within approximately 2 km from the
      drainage gates of the reservoir.

PMID- 19092187
TI  - Application of water framework directive in Hungary: development of biological
      classification systems.
AB  - The classification according to the Water Framework Directive (WFD) includes
      numerous challenges in contrast with the previously applied water qualification
      standards. The most important element of the ecological status, the biological
      one, is based on five groups of living organisms: phytoplankton, phytobenthon,
      macrophytes, macro-invertebrates and fish. The results of a three-year research
      project financed by the Ministry of Environment and Water (MoEW) and the
      Hungarian Academy of Sciences (HAS) are reported in this work. The objective of
      the project was the elaboration of a proposal for biological classification
      according to the WFD for the related groups of living organisms. In the course of
      the project the biological characteristics to be measured were selected for each
      of the above listed groups which served as the basic data for Biological Quality
      Elements (BQEs). In the BQEs we estimated the type-specific reference values for
      most of the Hungarian surface water types. Then we created the structure of the
      qualification system for these groups, including specification of class
      boundaries between the five classes for the Environmental Quality Ratio (EQR)
      values on the basis of expert estimation. A Non-Taxonomic Periphyton Index (NTPI,
      not included in the WFD) was also developed and tested for qualification. The
      elaborated classification systems were tested on the basis of existing scarce
      data for numerous Hungarian water types.

PMID- 19092188
TI  - Bioremediation of trichloroethylene contaminated groundwater using anaerobic
      process.
AB  - Anaerobic remediation of trichloroethylene (TCE) contaminated soil and
      groundwater was studied in laboratory setups. In this process fermentation of
      polymeric organic materials (POMS) produced volatile fatty acids (VFAs) that were
      electron donors in reductive dechlorination of TCE. Shredded peanut shell was
      selected as low cost POM and the experiments were set up in 500 ml Erlenmeyer
      flasks. In the setups, approximately 25 mg of leachate contaminated soil was used
      as the main source of microorganisms and about 5 g of shredded peanut shell (0.5
      2.36 mm) was added to produce VFAs for dechlorination of TCE. In the first set of
      experiments, fermentation of soil and shredded peanut shell was studied and it
      was found that VFAs were produced continuously with increasing concentration
      (5.63 mM as CH3COOH from the first day to 17.17 in the 10th day of the
      experiment). During the fermentation, concentration of ammonia-nitrogen was 22-50
      mg/L, the ratio of VFA to NH3 was 15.29-23.44 and pH was 5.24-6.00. These results
      show that the system was appropriate for microorganism activities. In the second
      set of experiments, TCE (approximately 48 mg/L) was added to the fermentation
      system and remediation of TCE by reductive dechlorination was studied. It was
      found that 0.04(+/-0.01) mg TCE adsorbed to a gram of soil and peanut shells at
      the beginning of the experiment and based on mass balance of the system, TCE
      concentration in water was linearly reduced at the rate of 0.0098 mg/hr.

PMID- 19092189
TI  - Abundance exchange models of fish assemblages along the Hudson River Estuary
      Gradient, New York.
AB  - The spatially explicit abundance exchange model (AEM) was built for four fish
      species: winter flounder (Pseudopleuronectes americanus), Atlantic silverside
      (Menidia menidia), eastern silvery minnow (Hybognathus regius), and striped bass
      (Morone saxatilis) along the Hudson River estuary gradient, New York. The fish
      and habitat data during 1974-1997 were used to develop and calibrate the AEM; and
      the fish data during 1998-2001 was used to validate the model. Preference indexes
      of fish species for dissolved oxygen, salinity, water temperature, and bottom
      substrates along the gradient were estimated; and these were used to compute
      habitat preference (HP) of the associated fish species. The species HP was a key
      variable in the AEM to quantify abundance and distribution patterns of the
      associated species along the gradient. The AEM could efficiently predict
      abundance and distribution patterns of all modeled species except striped bass.
      The model ability for predicting a local distribution range of a fish species
      with broad tolerance on changing environment like striped bass should be
      improved.

PMID- 19092190
TI  - Transport and biotransformation of organic carbon and nitrate compounds in
      unsaturated soil conditions.
AB  - The lack of drinking water was one of the hot environmental issues that focused
      on the contaminants released from the failure of sanitary systems. Organic carbon
      and nitrate compounds were concerned since they represented a potential risk to
      human health and environment. Mathematical modelling was an effective tool for
      understanding and estimating the fate and transport of contaminants. An organic
      carbon and nitrate compounds transport model was developed using the mass balance
      concept. Richards and multiplicative Monod equations supported the estimating of
      advection-dispersion transport and biodegradation processes, respectively. The
      numerical solutions were obtained using the MATLAB programme. The model
      capability was evaluated using pilot scale experimental data. The depth-averaged
      time series of pressure head and contaminants concentration profiles were
      measured several times a week during 91 days. Simulations were found to provide
      reasonable agreement with the observed data. The aerobic biodegradation zone was
      observed within 15 cm depth of soil column. Even though the column was operated
      for 91 days, soil microbes were enough to retard these contaminants. This
      confirmed that the developed model could be applied to simulate the transport of
      the contaminants under real time boundary conditions.

PMID- 19092191
TI  - Atrazine remediation in agricultural infiltrate by bioaugmented polyvinyl alcohol
      immobilized and free Agrobacterium radiobacter J14a.
AB  - Bench-scale sand column breakthrough experiments were conducted to examine
      atrazine remediation in agricultural infiltrate by Agrobacterium radiobacter J14a
      (J14a) immobilized in phosphorylated-polyvinyl alcohol compared to free J14a
      cells. The effects of cell loading and infiltration rate on atrazine degradation
      and the loss of J14a were investigated. Four sets of experiments, i) tracers, ii)
      immobilized dead cells, iii) immobilized cells, and iv) free cells, were
      performed. The atrazine bioremediation at the cell loadings of 300, 600, and 900
      mg dry cells l(-1) and the infiltration rates of 1, 3, and 6 cm d(-1) were tested
      for 5 column pore volumes (PV). The atrazine breakthrough results indicated that
      the immobilized dead cells significantly retarded atrazine transport. The
      atrazine removal efficiencies at the infiltration rates of 1, 3, and 6 cm d(-1)
      were 100%, 80-97%, and 50-70% respectively. Atrazine remediation capacity for the
      immobilized cells was not significantly different from the free cells. Both
      infiltration rate and cell loading significantly affected atrazine removal for
      both cell systems. The bacterial loss from the immobilized cell system was 10 to
      100 times less than that from the free cell system. For long-term tests at 50 PV,
      the immobilized cell system provided consistent atrazine removal efficiency while
      the atrazine removal by the free cells declined gradually because of the cell
      loss.

PMID- 19092192
TI  - Effects of electric polarization of indium tin oxide (ITO) and polypyrrole on
      biofilm formation.
AB  - The influence of electric polarization on primary adhesion and on biofilm
      formation was investigated. As substrata, indium tin oxide (ITO) and polypyrrole
      coatings were used because of their electric conductivity. The materials were
      polarized from -600 mV to +600 mV, switching every 60 seconds. Control was non
      polarized substrata. Primary adhesion under this regime was not strongly
      influenced, however, the morphology of the primary biofilm was obviously
      different from that of the control. Biofilm formation of the natural population
      of non-chlorinated drinking water, supplemented with nutrient in low
      concentration, was determined over 164 hours. While the biofilm on the control
      surface developed to a thickness of about 100 microm, on the pulsed polarized
      surface it reproducibly developed only to a very thin biofilm. Faster switching
      of the polarization (10 second) had no further influence. If the polarization
      routine was reduced to only twice a day (one hour), no influence on biofilm
      development was observed. These results indicate that fluctuating polarization at
      a rate of once per minute inhibits the physiological processes during biofilm
      formation during one week. Investigations are in process to determine further
      details of this effect in order to employ it for inhibition of biofouling.

PMID- 19092193
TI  - Mapping areas at risk of diffuse phosphorus losses to water: a pilot study of
      Lake Haderslev Dam, Denmark.
AB  - Haderslev Dam is a 272 ha lake in southern Denmark with a high recreational
      value. For decades the lake has been severely eutrophicated due to excessive
      phosphorus loading. Major point sources were cut off in the early 1990s and an
      upstream wetland was recreated. However, the ecological quality remains
      unsatisfactory. In this study we estimate the importance of agriculture on
      diffuse phosphorus (P) input to the lake by modelling combined with independent
      estimates for contributions from scattered dwellings not connected to a sewer and
      from background losses. We apply a newly developed Danish P index to the lake
      catchment for mapping of risk areas for diffuse phosphorus losses. For risk areas
      we suggest mitigation measures and estimate the effect of the mitigation measures
      on the total P loading of the lake as well as the associated costs.

PMID- 19092194
TI  - Importance of diffuse pollution control in the Patzcuaro Lake Basin in Mexico.
AB  - In the catchment area of the Lake Patzcuaro in Central Mexico (933 km2) the
      apportionments of erosion, sediment, nutrients and pathogen coming from thirteen
      micro basins were estimated with the purpose of identifying critical areas in
      which best management practices need to be implemented in order to reduce their
      contribution to the lake pollution and eutrophication. The ArcView Generalized
      Watershed Loading Functions model (AV-GWLF) was applied to estimate the loads and
      sources of nutrients. The main results show that the total annual contribution of
      nitrogen from point sources were 491 tons and from diffuse pollution 2,065 tons,
      whereas phosphorus loads where 116 and 236 tons, respectively during a thirty
      year simulation period. Micro basins with predominant agricultural and animal
      farm land use (56% of the total area) accounts for a high percentage of nitrogen
      load 33% and phosphorus 52%. On the other hand, Patzcuaro and Quiroga micro
      basins which comprise approximately 10% of the total catchment area and are the
      most populated and visited towns by tourist 686,000 people every year, both
      contributes with 10.1% of the total nitrogen load and 3.2% of phosphorus. In
      terms of point sources of nitrogen and phosphorus the last towns contribute with
      23.5% and 26.6% respectively. Under this situation the adoption of best
      management practices are an imperative task since the sedimentation and pollution
      in the lake has increased dramatically in the last twenty years.

PMID- 19092195
TI  - Fate and analysis of endocrine disrupting chemicals in some sewage treatment
      plants in Australia.
AB  - There are limited studies on the fate and levels of endocrine disrupting
      chemicals in sewage treatment plants in Australia. Research undertaken in Europe
      and North America has shown biologically significant levels of both oestrogenic
      and androgenic chemicals in sewage effluent. The aim of this work was to
      determine the oestrogenic and androgenic activities of raw and treated sewage
      from sewage treatment plants run by MidCoast Water, New South Wales, Australia.
      Oestrogenic and androgenic activities were measured using a yeast screen
      bioassay. Results showed that the raw effluent contained biologically significant
      levels of both oestrogenic (0.58-2.91 ng/l) and androgenic (216-480 ng/l)
      activities. Androgenic activity was significantly higher than oestrogenic
      activity, which was consistent with other Australian studies and was attributed
      to the higher levels of androgens in domestic waste from human excretion compared
      to oestrogens. Secondary treatment (using activated sludge) removed the majority
      of the oestrogenic and androgenic activity (up to 99%). Tertiary treatment by UV
      removed varying levels of oestrogenic (19-69%) and androgenic (5-55%) activities.
      A Membrane Bioreactor (MBR) at one of the STPs, which consists of an MBR followed
      by electrochlorination removed over 87% of the oestrogenic activity and over 98%
      of androgenic activity from raw sewage samples. However, levels which could be
      biologically significant still remained after secondary and tertiary treatment
      (>0.1 ng/l oestrogenic activity and >1 ng/l androgenic activity).

PMID- 19092196
TI  - Microbial diversity and population dynamics of activated sludge microbial
      communities participating in electricity generation in microbial fuel cells.
AB  - In this study, we performed microbial community analysis to examine microbial
      diversity and community structure in microbial fuel cells (MFCs) seeded with
      activated sludge from a municipal wastewater treatment plant in South Korea.
      Because anode-attached biofilm populations are particularly important in
      electricity transfer, the ecological characteristics of anode-attached biofilm
      microbes were explored and compared with those of microbes grown in suspension in
      an anode chamber. 16S rDNA-based community analysis showed that the degree of
      diversity in anode-attached biofilms was greater than that of the originally
      seeded activated sludge as well as that of the suspension-grown microbes in the
      anode bottle. In addition, Bacteroidetes and Clostridia grew preferentially
      during MFC electricity generation. Further phylogenetic analysis revealed that
      the anode biofilm populations described in this work are phylogenetically distant
      from previously characterized MFC anode biofilm microbes. These findings suggest
      that a phylogenetically diverse set of microbes can be involved in the
      electricity generation of MFC anode compartments, and that increased microbial
      diversity in anode biofilms may help to stabilize electricity production in the
      MFC.

PMID- 19092197
TI  - Eutrophication of agricultural streams: defining nutrient concentrations to
      protect ecological condition.
AB  - Inputs of nutrients (phosphorus, P, and nitrogen, N) to coastal and fresh waters
      can accelerate eutrophication, resulting in excessive aquatic plant growth,
      depletion of oxygen, and deleterious changes in abundance and diversity of
      organisms. Using long-term (approximately 1995-2005) monitoring data from
      agriculturally-dominated watersheds in southern Ontario and Quebec, Canada, we
      developed and tested several approaches for setting targets for N and P. Our
      research showed that it is possible to set scientifically-credible targets for
      total P and total N to protect ecological condition of streams in agricultural
      landscapes, and define achievable targets attainable following adoption of
      beneficial management practices.

PMID- 19092198
TI  - Degradation of hexachloroethane by Fenton's reagents.
AB  - The effect of hydrogen peroxide (H2O2) concentrations on the degradation of
      hexachloroethane (HCA) in the absence and the presence of tetrachloroethene (PCE)
      by Fenton's reagent was investigated at pH 3 with 1 mM iron(II) and H2O2
      concentrations ranging from 0.01 M to 2 M. HCA degradation in the absence of PCE
      increased with increasing H2O2 concentration between 0.2 M and 2 M. In the
      presence of PCE, HCA degradation was similar to that in the absence of PCE for
      H2O2 concentration up to 1 M, but significantly higher for 2 M H2O2. We propose
      that this increase is a result of elevated reductant radicals when PCE is
      present. This study highlights the need for further investigation into the
      degradation of contaminant mixtures at higher H2O2 concentrations.

PMID- 19092199
TI  - Nitrate removal by entrapped zero-valent iron nanoparticles in calcium alginate.
AB  - Zero-valent iron nanoparticles (nZVI) were successfully entrapped in calcium
      alginate beads. The potential use of this technique in environmental remediation
      using nitrate as a model contaminant was investigated. Kinetics of nitrate
      degradation using bare nZVI (approximately 35 nm dia) and entrapped nZVI were
      compared. Calcium alginate beads show promise as the entrapment medium for nZVI
      for possible use in permeable reactive barriers for groundwater remediation.
      Based on scanning electron microscopy images it can be inferred that the alginate
      gel cluster acts as a bridge that binds the nZVI particles together. Kinetic
      experiments with 100, 60, and 20 mg NO3--N L(-1) indicate that 50-73% nitrate-N
      removal was achieved with entrapped nZVI as compared to 55-73% with bare nZVI
      over a 2 h period. The controls ran simultaneously show little or no NO3--N
      removal. Statistical analysis indicates that there was no significant difference
      between the reaction rates of bare and entrapped nZVI. The authors have shown for
      the first time that nZVI can be effectively entrapped in Ca-alginate beads and no
      significant decrease in the reactivity of nZVI toward the model contaminant
      (nitrate here) was observed after the entrapment.

PMID- 19092200
TI  - Comparative reductions of bacterial indicators, bacteriophage-infecting enteric
      bacteria and enteroviruses in wastewater tertiary treatments by lagooning and UV
      radiation.
AB  - A two-year monitoring program of microbiological and physical-chemical parameters
      at 2 waste water treatment plants (WWTPs) in Mallorca (Spain) was performed in
      order to (1) evaluate the efficiency of lagooning and UV radiation as tertiary
      treatment processes; (2) determine the characteristics of wastewater effluent for
      its potential agricultural reuse; and (3) establish correlations between
      bacteriological and virological parameters. The presence of currently established
      bacterial indicators (total coliforms, faecal coliforms, Escherichia coli,
      enterococci, and spores of sulphite-reducing clostridia), virological
      (enteroviruses, somatic coliphages, F-specific coliphages, and phages infecting
      Bacteroides fragilis and Bacteroides thetaiotaomicron), and helminth eggs were
      tested during this study. Bacterial and viral indicators were removed at least
      with one log reduction in the lagooning system, and to a lesser extent with UV
      radiation treatment. The lagooning system was less efficient in removing phages
      and viruses than were bacterial indicators, with the exception of F-specific
      phages. Phages of B. fragilis and B. thetaiotaomicron were less removed than all
      of the other microbiological parameters. In the UV-radiation treatment, however,
      the faecal coliforms proved the most sensitive, while clostridial spores, somatic
      coliphages, Bacteroides phages, and enteric viruses were the more resistant.
      Helminth eggs were not detected in any samples from effluents of either the
      secondary or tertiary treatments.Indicator levels in both treatments met the
      established regulations of both local and national authorities for the disposal
      or reuse of wastewater in irrigation for non-human crop. We demonstrate that
      somatic coliphages are effective indicators of enteric viruses in both of the
      WWTPs studied.

PMID- 19092201
TI  - Identification of critical source areas for non-point source pollution in Miyun
      reservoir watershed near Beijing, China.
AB  - Miyun Reservoir is the major water source for Bijing, China. Currently, the water
      quality of Miyun reservoir is meso-trophic, mainly due to the non-point source
      pollution (NPS) in the watershed. Phosphorus (P) is the limited factor. In this
      paper, Chaohe River basin, upstream of the Miyun Reservoir, is chosen as the
      study area, A modified P Index was developed to identify critical source areas
      (CSAs) of non-point source pollution by analyzing local hydrological and
      meteorological data, land use, soil, soil conservation, farmland management,
      population density, and livestock. The factors of livestock and population
      density are new factors added to the P Index system based on the actual local
      characteristics. It was found that the loss P from high-risk area accounts for
      only 7.95%. These areas are located mainly along streams. Livestock factor and
      the population density factor are most closely related to the CSAs downstream of
      Chaohe River basin. The management strategies are outlined according to the
      distribution characteristics of the critical source areas.

PMID- 19092202
TI  - Natural cadmium loading and balance in a non-polluted rice paddy field in Japan.
AB  - We determined the natural Cd balance in a cultivated rice paddy field in Japan.
      The main sources of Cd in the non-polluted paddy field were phosphorus fertilizer
      and precipitation (annual input of Cd, 2,000 mg ha(-1) and 1,020 mg ha(-1),
      respectively). These sources account for 95% of the total input of Cd (3,192 mg
      ha(-1)). The actual increase of Cd in the soil was 0.0016 mg kg(-1), we thus
      consider Cd in soil increases only slightly as a result of rice culture. This
      study indicates that it is difficult to reduce Cd loading by irrigation water
      treatment in a non-polluted paddy field. This further indicates that once a field
      is polluted by Cd it is difficult to decrease the accumulated Cd by the ordinary
      cultivation of rice plants.

PMID- 19092203
TI  - Modelling nutrient emissions and the impact of nutrient reduction measures in the
      Weser river basin, Germany.
AB  - To implement the European Water Framework Directive (WFD) into German law,
      measures have to be taken to reduce the unacceptably high nutrient input into
      rivers. To identify the most effective measures, the sources and pathways of
      nutrient emissions into rivers have to be quantified. Therefore, the MONERIS
      model is applied, which quantifies nutrients emissions into river basins, via
      various point and diffuse pathways, as well as nutrient load in rivers. Most
      nitrogen emissions come from groundwater flow (43%), tile drainages (30%), and
      point sources (12%), whereas most phosphorus emissions come from groundwater flow
      (31%), point sources (23%), erosion (13%) and overland flow (12%). Because of
      their great distance from the river basin outlet, the southern sub-basins Werra
      and Fulda-Diemel have an 8% reduction in their nitrogen loads and a 15% and 16%
      reduction in their phosphorus loads, respectively. This reduction is due to
      retention in the main part of the river Weser. For the choice of the most
      effective measures, the different retention in the river is relevant.

PMID- 19092204
TI  - Limitations of a membrane gradostat bioreactor designed for enzyme production
      from biofilms of Phanerochaete chrysosporium.
AB  - Growing interest has been shown in the continuous production of high-value
      products such as extracellular secondary metabolites used in the biotechnology,
      bioremediation and pharmaceutical industries. These high-value extracellular
      secondary metabolites are mostly produced in submerged fermentations. However,
      the use of continuous membrane bioreactors was determined to be highly
      productive. A novel membrane bioreactor, classified as a membrane gradostat
      reactor (MGR) was developed to immobilize biofilms to produce extracellular
      secondary metabolites continuously using an externally unskinned and internally
      skinned membrane. Anaerobic zones were identified in the MGR system when air was
      used for aeration. To improve the MGR system, limitations related to the
      performance of the bioreactor were determined using P. chrysosporium. A DO
      penetration depth of +/-450 microm was identified after 264 h, with the anaerobic
      zone thickness reaching approximately 1,943 microm in the immobilised biofilms.
      The penetration ratio, decreased from 0.42 after 72 h to 0.14 after 264 h. This
      led to the production of ethanol in the range of 10 to 56 mg/L in the MCMGR and 7
      to 54 mg/L in SCMGR systems. This was attributed to an increase in beta-glucan
      within immobilised biofilms when an oxygen enriched aeration source was used.
      Increasing lipid peroxidation and trace element accumulation was observed with
      the use of an oxygen enriched aeration source.

PMID- 19092205
TI  - Water quality improvement by implementation of Proposition O in the Los Angeles
      river watershed, California.
AB  - Proposition O was created to help the City of Los Angeles comply with the Total
      Maximum Daily Load (TMDL) requirements under the Clean Water Act. In this study,
      the effectiveness of the Proposition O projects in Los Angeles River watershed
      was examined to show whether it achieves the goal of meeting water quality
      standards. Our analysis shows the most effective single project will remove at
      most 2% of pollutant loads from Los Angeles River Watershed and will not achieve
      TMDL compliance, although several projects can make important contributions to
      achieve compliance. The ranking results show that the projects that treat the
      runoff from the largest drainage area have the greatest impact on the water
      quality of Los Angeles river.

PMID- 19092206
TI  - Importance of investment decisions and rehabilitation approaches in an ageing
      wastewater pipeline network. A case study of Oslo (Norway).
AB  - As Oslo Vann og Avlopsetaten (VAV, meaning Water and Sewage Department) looks
      into the future, it is faced with a quandary-to replace old pipelines or to
      continue maintaining them. The primary goal is to improve the level of service.
      The secondary goals are to rejuvenate the system and stem the decline in capital
      value. In 1991-2006, the Operation and Maintenance expenses (O&M) were far higher
      than the investments, and the network aged as its capital value plummeted.
      However, if the funds are insufficient, the self-financing Oslo VAV would have to
      turn to the consumers for help. Will the consumers pay more to have a 'younger'
      system? What if they are happy with the 'status quo' and are unconcerned about
      the falling capital value? Should the pipelines be depreciated over a longer
      period than the 40 years which is adopted now? Should the economic method be
      replaced by a more engineering-based method, whereby the pipes are assessed 'on
      merit'-on the basis of their service lives? There are numerous issues and a good
      decision will ease the road ahead. This paper, using Life Cycle Costing Analysis
      (LCCA) and scenarios therein, looks at how Oslo VAV could strike a balance
      between expending on O&M, investing in upgrading the network, and decelerating
      the ageing of the network while augmenting the capital value, and what is the
      best attainable set of targets they could aim for, at the end of the next 20
      years. The two approaches mentioned above are compared with each other. It is
      seen that a rehabilitation programme based on the pipes performance approach is
      preferable to one guided by an economic lifetime approach, when the motive is to
      optimise expenditure and also improve the level of service.

PMID- 19092207
TI  - Assessing necessary nutrient reduction for measurement planning in groundwater
      bodies.
AB  - For the Federal State of Lower Saxony, Germany, nitrogen management options are
      developed and implemented in three pilot areas using new participation approaches
      and technologies suitable for programs of measures to reduce diffuse pollution
      from agriculture. As a target value for water protection measures a nitrate
      concentration in percolation water of 50 mg/l as an average for a larger area
      defined by the groundwater bodies and their hydrogeological subdivisions has been
      defined. An integrative emission model is used to simulate the interactions
      between agricultural practice, nitrogen surpluses and the nitrogen flow through
      the soil and aquifer to the outflow into surface waters. The actual nitrate
      concentrations in percolation water are calculated for the entire Federal State
      of Lower Saxony considering site-characteristics, N-surpluses, water balance and
      denitrification in the soil. The tolerable N-surpluses needed to meet the
      environmental target are quantified as averages for each of the hydrogeological
      subdivisions by "backward" calculation using this model system. The required
      reduction of N-surpluses was estimated by comparing the tolerable N-surpluses
      with the actual state of nitrogen emission. For the evaluation of the amount and
      efficiency of water protection measures, the required reduction of N-surpluses to
      accomplish the environmental target is quantified, using the current status as a
      reference.

PMID- 19092208
TI  - Integration of aquatic ecology and biological oceanographic knowledge for
      development of area-based eutrophication assessment criteria leading to water
      resource remediation and utilization management: a case study in Tha Chin, the
      most eutrophic river of Thailand.
AB  - This research was carried out in Tha Chin Watershed in the central part of
      Thailand with attempts to apply multidisciplinary knowledge for understanding
      ecosystem structure and response to anthropogenic pollution and natural impacts
      leading to a proposal for an appropriate zonation management approach for
      sustainable utilization of the area. Water quality status of the Tha Chin River
      and Estuary had been determined by analyzing ecological, hydrological, and
      coastal oceanographic information from recent field surveys (during March 2006 to
      November 2007) together with secondary data on irrigation, land utilization, and
      socio-economic status.Results indicated that the Tha Chin River and Estuary was
      eutrophic all year round. Almost 100% of the brackish to marine areas reflected
      strongly hypertrophic water condition during both dry and high-loading periods.
      High NH(4)(+) and PO(4)(3-) loads from surrounding agricultural land use, agro
      industry, and community continuously flew into the aquatic environment.
      Deteriorated ecosystem was clearly observed by dramatically low DO levels (ca 1
      mg/l) in riverine to coastal areas and Noctiluca and Ceratium red tide outbreaks
      occurred around tidal front closed to the estuary. Accordingly, fishery resources
      were significantly decreased. Some riverine benthic habitats became dominated by
      deposit-feeding worms e.g. Lumbriculus, Branchiura, and Tubifex, while estuarine
      benthic habitats reflected succession of polychaetes and small bivalves. Results
      on analysis on integrated ecosystem responses indicated that changing functions
      were significantly influenced by particulates and nutrients dynamics in the
      system.Based on the overall results, the Tha Chin River and Estuary should be
      divided into 4 zones (I: Upper freshwater zone; II: Middle freshwater zone; III
      Lower freshwater zone; and IV: Lowest brackish to marine zone) for further
      management schemes on water remediation. In this study, the importance of habitat
      morphology and water flow regimes was recognized. Moreover, nearshore extensive
      shrimp culture ponds, irrigation canals, and surrounding mangrove habitats
      belonging to local households seemed to act as effective natural water treatment
      system that can yet provide food resources in turns. These remediation-production
      integrated functions should be deserved depth considerations for water quality
      development of the Tha Chin areas.

PMID- 19092209
TI  - Water environment conservation in a closed water body by high concentrated oxygen
      water.
AB  - In this study, the method of using high concentrated oxygen water to purify the
      bottom sediment was confirmed to be effective. The high concentrated oxygen
      dissolver was developed and the lab scale experiment was performed. High rate,
      high efficiency oxygen dissolver was developed, the optimum running condition of
      the apparatus and the method of producing high concentrated oxygen water was
      discussed and determined in this study. In addition, the effective prevention of
      phosphorus release from anaerobic bottom sediment was also studied. As a result,
      it is found that high concentrated oxygen water was effective for prevention of
      phosphorus release from anaerobic bottom sediment. On the basis of the
      fundamental knowledge from the laboratory-scale study, pilot scale apparatus was
      set up and the pilot study was carried out. It is showed that the introduction of
      high concentrated oxygen water did not destroy the thermocline of dam reservoir.

PMID- 19092210
TI  - Design and operating experiences of municipal MBRs in Europe.
AB  - The number of membrane bioreactor (MBR) installations is increasing worldwide,
      not only for small-scale industrial WWTPs but also for larger-scale municipal
      WWTPs. In Europe, MBR has been installed in municipal WWTPs since late 1990s, and
      more than 100 full-scale plants are operated at the moment. In this paper,
      present state of European municipal MBRs is described in terms of design and
      operating conditions, as well as operating problems and their solutions, based on
      the information collected from 17 full-scale WWTPs by interview and questionnaire
      survey. Decisive factors of MBR installation at these plants were footprint and
      effluent quality. Full-aerobic and pre-denitrification were the most common
      reactor configurations, nearly half of them being equipped with independent
      filtration tanks. Operating conditions of bioreactor and filtration, including
      membrane flux and cleaning strategy, were different from plant to plant, as a
      result of plant-specific optimization experiences, even among the similar type of
      membrane. Operating problems specific for MBR were reported, including
      blocking/failure of pre-screen, sludging/hair-clogging of membrane, damage on
      membrane unit, air in permeate pipes, as well as conventional troubles including
      occurrence of scum and initial trouble in instrumentation and control systems.
      Aspects for further optimization of MBR design were also pointed out by the
      operators.

PMID- 19092211
TI  - Estimation of pollutant loads considering dam operation in Han River Basin by
      BASINS/Hydrological Simulation Program-FORTRAN.
AB  - Effective watershed management often demands qualitative and quantitative
      predictions of the effect of future management activities as arguments for policy
      makers and administration. The BASINS geographic information system was developed
      to compute total maximum daily loads, which are helpful to establish hydrological
      process and water quality modeling system. In this paper the BASINS toolkit HSPF
      model is applied in 20,271 km(2) large watershed of the Han River Basin is used
      for applicability of HSPF and BMPs scenarios. For proper evaluation of watershed
      and stream water quality, comprehensive estimation methods are necessary to
      assess large amounts of point source and nonpoint-source (NPS) pollution based on
      the total watershed area. In this study, The Hydrological Simulation Program
      FORTRAN (HSPF) was estimated to simulate watershed pollutant loads containing dam
      operation and applied BMPs scenarios for control NPS pollution. The 8-day
      monitoring data (about three years) were used in the calibration and verification
      processes. Model performance was in the range of "very good" and "good" based on
      percent difference. The water-quality simulation results were encouraging for
      this large sizable watershed with dam operation practice and mixed land uses;
      HSPF proved adequate, and its application is recommended to simulate watershed
      processes and BMPs evaluation.

PMID- 19092212
TI  - Reductive characteristics of washed-off pollution loads by best management
      practices.
AB  - Best management practices (BMPs) were used to reduce the NPS in various fields.
      The Korean Ministry of Environment has developed a total maximum daily load
      (TMDL) and adapted it to prevent water resources from pollutants in four major
      rivers. However, many water bodies in Korea are still polluted. It is anticipated
      that the NPS pollution flows into the water bodies without treatment. Nowadays,
      BMPs are enforced to reduce the NPS pollutant in Korean TMDL.This paper analyzes
      the characteristics of the reduced pollution loads by two different BMPs. We also
      calculate the reduced pollutant mass and the reduced pollutant loading rate to
      help make a plan for the pollution reduction in the Korean TMDL.The
      characteristics of the pollutant reduction in the BMPs were revealed through
      analysis of the EMC, first flush phenomenon and reduced pollution loads.
      Integrated facilities which combined two facilities were more effective to reduce
      the pollutant than the single and it was better to remove the beginning of the
      runoff as a first flush effectively than treat all runoff in the facilities.

PMID- 19092213
TI  - Evaluation of strips of centipede grass for sediment load reduction.
AB  - Reddish sediment runoff from agricultural fields results in coastal environmental
      problems in Okinawa, Japan. Recent studies have demonstrated the effectiveness of
      strips of centipede grass (Eremochloa ophiuroides (Munro) Hack.), a perennial
      turf grass, in reducing the sediment loads from farmlands. However, sufficient
      information has not been provided to determine the appropriate strip
      specifications in the grass strip design. This study evaluated centipede grass
      strips for reduction of reddish sediment runoff from farmlands in Okinawa, Japan.
      A numerical model simulating the reddish sediment transport in the grass strip
      was constructed to determine the sediment removal efficiency of the strip. The
      model was verified using data obtained from field plot experiments with the grass
      strips under natural conditions. The sensitivity analysis of the model showed
      that the length of the grass strip (i.e. the dimension of the strip in the
      direction of flow) and unit inflow discharge have a great effect on sediment
      removal efficiency. The sediment removal efficiency obtained from the model
      simulation increased with the length of the strip and the increment of the
      efficiency decreased with the length of the strip. Therefore, these results
      indicate that the effective and efficient length of a centipede grass strip is 3
      m for the reduction of reddish sediment loads under typical farmland conditions
      in Okinawa.

PMID- 19092214
TI  - Treatment of saline, acidic, metal-contaminated groundwater from the Western
      Australian Wheatbelt.
AB  - Managing acidic, metal-containing saline ground and drainage waters in the
      Wheatbelt of Western Australia is an environmental and economic challenge.
      Sulfate-reducing fluidised bed bioreactors are shown to be technically capable of
      treating high salt, low pH, metal containing waters from the town of Narembeen in
      the Wheatbelt so as to reduce acidity and to remove most of the undesirable metal
      contaminants. The hydraulic residence time (HRT) limit for a stable process with
      groundwater from the region of Narembeen was >16 hours. The maximal rate of
      sulfate reduction in the laboratory system treating Narembeen groundwater was
      similar to rates observed in comparable applications of the process at other
      sites, ca. 3 g sulfate (L-reactor)(-1) day(-1). Salts that are relatively free of
      metal contaminants can be produced from water that has been treated by the
      sulfate-reducing fluidised bed bioreactor. It is unlikely that metal
      precipitates, captured from Wheatbelt waters by the process, would be of economic
      value. If sulfate-reducing fluidised bed reactors were considered technologically
      appropriate at larger scale, the decision to use them would be based on the
      necessity to take action, the comparative effectiveness of competing
      technologies, and the relative costs of competing technologies.

PMID- 19092215
TI  - Microbial ecology and performance of nitrifying bacteria in an aerobic membrane
      bioreactor treating thin-film transistor liquid crystal display wastewater.
AB  - This study was conducted to evaluate the long-term performance of an aerobic
      membrane bioreactor (MBR), treating TFT-LCD wastewater containing dimethyl
      sulphoxide (DMSO), monoethanolamine (MEA) and tetra-methyl ammonium hydroxide
      (TMAH), which are recognized as slow-biodegradable organic compounds containing
      nitrogen and can release significant amount of ammonia during biodegradation.
      Moreover, many studies have reported that certain organic compounds can
      potentially inhibit nitrification of AOB, but limited information is available
      regarding the effects of TFT-LCD wastewater compounds on nitrification
      performance and microbial ecology of nitrifying bacteria. In general, the aerobic
      MBR achieved satisfactory conversion efficiency for DMSO, MEA, TMAH, and ammonia,
      except that a sudden inhibition on MEA degradation was observed for a transition
      period when the influent feed switched from synthetic to real TFT-LCD wastewater.
      Furthermore, the terminal restriction fragment length polymorphism (T-RFLP)
      methodology was applied to monitor the microbial ecology of nitrifying bacteria
      in the aerobic MBR. The results suggested that Nm. marina or Nm. cummunis were
      the dominant AOB population in the aerobic MBR fed with synthetic TFT-LCD
      wastewater, while Nitrosospira became dominant in the aerobic MBR fed with real
      TFT-LCD wastewater. For the NOB population, both Nitrobacter and Nitrospira were
      present during this study. Finally, the results of batch experiments, which were
      conducted to evaluate the effects of DMSO, MEA, and TMAH on nitrification
      activity, indicated that MEA and TMAH became inhibitory to nitrifying bacteria at
      concentrations of 250 and 50 mg/L, respectively, while DMSO did not at
      concentrations up to 100 mg/L.

PMID- 19092216
TI  - Modeling Cd2+ sorption onto ferrihydrite in the presence of phthalic acid.
AB  - Cadmium sorption by ferrihydrite in the presence of phthalic acid was examined
      over a range of pH (4.0 approximately 8.5) conditions and sorbate/sorbent ratios.
      The presence of phthalic acid enhanced Cd(2+) sorption by forming ternary
      complexes on ferrihydrite surface, especially at low pH, but for high pH and high
      total organic ligand/Fe(mmol/mol) ratios, it decreased Cd(2+) sorption onto
      ferrihydrite by forming soluble complexes with the phthalate in solution. In
      binary systems, Cd(2+) and phthalic acid sorption by ferrihydrite was well
      reproduced using the diffuse layer model with sorption constants derived from the
      experimental data. Prediction using the optimised binary sorption constants for
      Cd(2+) sorption onto ferrihydrite in the presence of phthalic was poor and
      achieving a good fit required the inclusion of two additional ternary complexes.

PMID- 19092217
TI  - Learning Bayesian networks based diagnosis system for wastewater treatment
      process with sensor data.
AB  - Contemporary technical capabilities allow an operator to easily monitor and
      control several remote wastewater treatment processes simultaneously but an on
      line automatic diagnostic system has not yet been installed. In this paper, an on
      line diagnostic system is proposed, designed and implemented for the lab-scale
      five-stage step-feed Enhanced Biological Phosphorus Removal plant based upon a
      learning Bayesian network. In order to practically diagnose wastewater treatment
      processes, a lab-scale pilot plant was built and the proposed on-line diagnostic
      method was applied to evaluate the performance of the algorithm. In experimental
      results, real abnormal conditions occurred 21 times in a three month period. The
      suggested on-line diagnosis system made correct predictions 14 times and
      incorrect predictions 7 times. Moreover, a comparison of the prediction results
      of the Bayesian model and learning Bayesian model clearly show that learning
      algorithm became more effective as time passed.

PMID- 19092218
TI  - Municipal wastewater treatment by a periodic biofilter with granular biomass.
AB  - The paper reports the results obtained during an experimental campaign aimed at
      transferring aerobic granulation to a demonstrative SBBGR system (i.e., a
      submerged biofilter that operates in a "fill and draw" mode) for the treatment of
      municipal wastewater by financial support of the European Commission, within the
      framework of Life-Environment Programme (PERBIOF Project; www.perbiof
      europe.com). The results show that following the generation of granular biomass
      during the start-up period, the SBBGR was able to remove 80-90% of COD, total
      suspended solids and ammonia occurring in primary effluent from a municipal
      wastewater treatment plant even when the minimum hydraulic residence time (i.e.,
      4 h) was investigated. The process was characterised by a sludge production
      almost one magnitude order lower than commonly reported for conventional
      treatment plants. The granular biomass was characterised by a high density (i.e.,
      150 gTSS/L(biomass)) that allowed a biomass concentration as high as 35
      kgTSS/m(3)(bed) to be achieved. Proteobacteria were found as main microbial
      components of the granular biomass by applying Fluorescence In Situ Hybridization
      (FISH). No significant changes in microbial composition were observed during
      reactor operation.

PMID- 19092219
TI  - Bacterial contamination of raw vegetables, vegetable-related water and river
      water in Ho Chi Minh City, Vietnam.
AB  - The study attempts to identify the potential routes of bacterial infection via
      consumption of raw vegetables, drinking water and vegetable-related water in Ho
      Chi Minh City (HCMC). Vegetables in the markets and restaurants had higher total
      coliforms and E. coli counts than the vegetables at the vegetable cultivation
      fields. In search of the potential contamination sources, it was found that
      vegetables are washed in nearby canals after harvesting. Those canals are
      contaminated with human and animal excreta, which in turn may contaminate the
      vegetables. At the markets, although the tap water was found to be free of
      microbes, contaminated and non-contaminated vegetables are mixed and washed in
      the same bowl, which may bring about further spreading of infectious bacteria.
      The results of this study suggested that an integrated countermeasure that
      incorporates reducing microbial contamination of canals, raising the awareness of
      microbial infection among the local farmers and wholesalers, and providing enough
      clean water to the food markets should be implemented to reduce the incidence of
      food-borne illness in HCMC.

PMID- 19092220
TI  - Electrochemical incineration of vinasse in filter-press-type FM01-LC reactor
      using 3D BDD electrode.
AB  - This work shows results obtained in the electrochemical incineration of a
      synthetic vinasse with initial chemical oxygen demand (COD) of 75.096 g L(-1) in
      aqueous media (which resembles vinasse industrial wastewater). Electrolyses in a
      filter-press-type FM01-LC electrochemical reactor equipped with a three
      dimensional (3D) boron doped diamond electrode (BDD) were performed at Reynolds
      values between 22 <or= Re <or= 109, and a fixed current density of 10 mA cm(-2).
      The electrochemical incineration achieved up to 97% in vinasse mineralization
      with current efficiencies that surpass unity and energy consumption of 168 KW-h
      m(-3), at Re =109. The mineralization of vinasse indicates that such degradation
      occurs via hydroxyl radicals formed by the oxidation of water on the BDD surface.
      Experimental data revealed that hydrodynamic conditions slightly influence the
      vinasse degradation rate and current efficiency, indicating that the oxidation
      involves a complex pathway.

PMID- 19092221
TI  - Effects of salinity on the morphological characteristics of aerobic granules.
AB  - Saline wastewater is ubiquitous in industries. The present study reports the
      effects of salinity on the morphological properties of aerobic granules. Within a
      wide range of salinity from 1% to 5%, good aerobic granules were successively
      cultured in sequencing batch reactors (SBRs). It was found by scanning electron
      microscope (SEM) analysis that the granular surface turned to be smoother and
      more regular with increase of salinity, and under lower salinity (1%) the microbe
      was cocci-dominated, while under higher salinity (5%) the microbe was filaments
      dominated. As a result of size distribution analysis, the granules were found to
      grow faster, larger and with a wider size spectrum under higher salinity.
      However, the porosities of the granules under the salinity of 1%, 2.5% and 5%
      were 0.90, 0.89 and 0.82, respectively, indicating that higher salinity may
      result in more compact granules. It can be concluded from this study that
      formation of large and compact granules is possible under salinity as high as 5%
      and filamentous microorganisms did not necessary lead to sludge bulking and
      granule breakage.

PMID- 19092222
TI  - Efficiency of removal of nitrogen, phosphorus, and zinc from domestic wastewater
      by a constructed wetland system in rural areas: a case study.
AB  - The effluent from the combined household wastewater treatment facilities used in
      unsewered areas of Japan is generally high in nitrogen (N) and phosphorus (P). In
      Japan, environmental quality standards for zinc (Zn) pollution were enacted
      recently because of the toxicity of Zn to aquatic ecosystems. In 2004 a fallow
      paddy field at the Koibuchi College of Agriculture and Nutrition was converted
      into a surface-water-flow constructed wetland (500 m(2)) to clean the effluent
      from the combined household wastewater treatment facility of a dormitory (100
      residents) before discharge to a pond. We evaluated N and P removal efficiencies
      and the fate of soluble Zn in the wetland from April 2006 to March 2007. Wetland
      influent contained an average of 18.3 mg L(-1) total N and 1.86 mg L(-1) total P.
      In the effluent from the wetland, average total N concentration was 10.3 mg L(-1)
      and average total P was 0.90 mg L(-1). Average removal rates were 0.37 g m(-2) d(
      1) for total N and 0.050 g m(-2) d(-1) for total P (percentage removal rates of
      40% and 48%, respectively). Soluble Zn concentration decreased from 0.041 in the
      influent to 0.023 mg L(-1) after passing through the wetland. The average Zn
      removal rate during the year was 0.0007 g m(-2) d(-1) (percentage removal rate
      37%).

PMID- 19092223
TI  - Physiological heterogeneity of suspended microbial aggregates.
AB  - Suspended microbial aggregates, which are always in dynamic equilibrium with
      suspended cells and cells attached to surface, are very common structures in
      natural and engineering environmental systems. To study and design
      physiologically diverse suspended microbial aggregates the physiological
      classification of chemotrophic prokaryotes in 12 groups formed by four
      evolutionary periods (fermenting, anaerobic respiring, microaerophilic and
      facultative aerobic, aerobic prokaryotes) and three parallel lines (Gram
      negative, Gram-positive Eubacteria, and Archaea) could be used. This type of
      physiological heterogeneity has been studied in microbial granules using
      fluorescence in situ hybridization, identification of 16S rRNA genes, and
      conferring the physiological properties from the description of the species. In
      spherical granules with diameter of 2.4 mm cells of aerobes were spread to the
      depth 0.55 mm below surface (85% of granule volume), facultative anaerobes
      dominated between the depths 0.55 mm and 0.85 mm (13% of granule volume), and
      anaerobes were concentrated at the depths from 0.85 to 1.0 mm (2% of granule
      volume). Percentages of aerobic, facultative anaerobic, and anaerobic species in
      granules, identified by 16S rRNA gene sequencing, were 69%, 9%, and 2% of total
      number of bacterial clones, respectively. Another type of physiological
      heterogeneity on the cellular level was due to the changes of cell physiological
      status during cell cycle. This type of heterogeneity has been studied in the
      populations of Escherichia coli, Bacillus megaterium, Saccharomyces cerevisiae,
      and Candida tropicalis. A significant proportion of cells from the exponential
      phase were killed after 10 min treatment with 1% solution of allyl alcohol, which
      specifically kills cells with high activity of alcohol dehydrogenase (ADH).
      However, there was no such effect in starved cell population. Percentage of cells
      with high activity ADH in microbial population can be used to monitor its
      physiological status. Physiological diversity of ecosystem may be due to
      mechanical mixing of cells from the different inflows. An example of such system
      is an ecosystem of aeration tank in municipal wastewater treatment plant. This
      ecosystem contains a mechanical mixture of dead anaerobic and live aerobic
      bacteria as well as attached and suspended cell aggregates supplied from
      anaerobic digester, raw sewage, and settling tank.

PMID- 19092224
TI  - Long-term impacts of pasture irrigation with treated sewage effluent on shallow
      groundwater quality.
AB  - The study investigated the effects of 26 years of effluent irrigation on chemical
      and bacteriological quality of shallow (<3.0 m) groundwater. Annual loading rates
      for N and P exceeded pasture requirements, while trace metals were either lower
      or higher than guideline limits. Effluent irrigation removed TN (44-71%), TP
      (80%), Cr (96%) and coliform bacteria (87-99.9%) while Zn, Cu and Cd removal was
      negligible probably due to their enhanced mobility. Analysis of groundwater
      samples from effluent-irrigated and non-irrigated control sites showed that
      effluent irrigation increased the levels of all measured parameters compared to
      the control. Average groundwater quality parameters from effluent-irrigated sites
      compared to the control were: pH (6.1 vs. 5.7), EC (0.71 vs. 0.53 dS m(-1)),
      concentrations (mg L(-1)) for TP (2.3 vs. 0.3), DP (1.0 vs. 0.1), TN (15.1 vs.
      2.5), NH(4)-N (2.6 vs. 0.5), NO(3)-N (4.1 vs. 1.3), Zn (0.4 vs. 0.05), Cu (0.13
      vs. 0.02), Cd (0.05 vs. 0.01) and Cr (0.06 vs. 0.03). Across effluent-irrigated
      sites, FC and TC were 25 and 288 cfu/100 ml, respectively, versus nil for the
      control. Overall, effluent irrigation led to groundwater contamination by N, P,
      trace metals and coliform bacteria, which could threaten the long-term
      sustainability of the practice.

PMID- 19092225
TI  - Settling velocity of particulate pollutants from combined sewer wet weather
      discharges.
AB  - Settling velocities of TSS and of particulate pollutants (COP, PDCO, PTKN, PCu,
      PPb, PZn, PPAH) measured on a wide range of wet weather flow (WWF) samples
      collected at different levels of the Parisian combined sewer system are reported.
      The recorded V30 (0.01 to 0.1 mm s(-1)) and V50 (0.09 to 0.6 mm s(-1)) values
      exceed by a factor 10 those of dry weather sewage and also exceed the values
      measured for pavement runoff. These values lie however often below the 0.28 mm s(
      1) reference value considered in France for the design of WWF settling
      facilities. A decrease in settleability is observed between a small upstream
      catchment and larger scaled downstream catchments. The settling behaviour of
      particulate pollutants varies depending on the considered parameter and can
      differ significantly from the TSS behaviour, due to a non homogeneous
      distribution of micropolluants over the different classes of particles. PZn and
      PTKN appear far less settleable than TSS, whereas PPAH show higher settleability.

PMID- 19092226
TI  - Biofilm formation by a biotechnologically important tropical marine yeast
      isolate, Yarrowia lipolytica NCIM 3589.
AB  - Biofilm formation by Yarrowia lipolytica, a biotechnologically important fungus
      in microtitre plates, on glass slide surfaces and in flow cell was investigated.
      In microtitre plates, there was a short lag phase of adhesion followed by a
      period of rapid biofilm growth. The fungus formed extensive biofilms on glass
      slides, whereas in flow-cells a multicellular, three-dimensional microcolony
      structure was observed. The isolate formed biofilms in seawater and in fresh
      water media at neutral pH when grown in microtitre plates. The carbon sources
      differentially affected formation of biofilms in microtitre plates. Lactic acid,
      erythritol, glycerol, glucose and edible oils supported the formation of
      biofilms, while alkanes resulted in sub-optimal biofilm development. A variation
      in the morphology of the fungus was observed with different carbon sources. The
      results point to the possible existence of highly structured biofilms in varied
      ecological niches from where the yeast is isolated.

PMID- 19092227
TI  - The differential impact of resolution methods on the operational scores of gender
      and ethnic groups.
AB  - In the scoring of performance assessments, when two raters assign different
      ratings some method must be used to resolve the discrepant ratings to form an
      operational score for reporting. This study investigated the differential impact
      of various resolution methods on the operational scores for gender and ethnic
      groups. The mean operational scores, and the passing rates for each group on two
      essay prompts were compared using three resolution methods (rater mean, tertium
      quid, and parity). The results indicated that for female and African American
      students, resolution typically resulted in greater reduction of mean operational
      ratings and passing rates than for those of their male or White counterparts.
      Differential item functioning (DIF) analyses were conducted using IRT-based
      logistic regression models. No apparent gender-related DIF was detected. Although
      uniform DIF was found for the ethnic groups, the effect was small, and there was
      not enough evidence to support the hypothesis that DIF could be associated with a
      resolution method.

PMID- 19092228
TI  - A Rasch measurement analysis of the use of cohesive devices in writing English as
      a foreign language by secondary students in Hong Kong.
AB  - This paper investigated the use of three types of cohesive devices, that is,
      reference, conjunction and lexis, used in writing the English as a Foreign
      Language (EFL) essays for students in secondary year 2, 4 and 6 in Hong Kong.
      Fifty students from each of the three forms (N = 150) provided narrative and
      descriptive essays for analysis which were marked by two competent English
      teachers by counting the frequency of writing devices used per 100 words.
      Initially, 14 cohesive devices (items) were counted as items for analysis, but
      two devices (items) were deleted as not fitting a Rasch measurement model. The
      RUMM2020 computer program with the partial credit model was used to create a
      linear scale of Writing Devices Used with twelve items: two for references, four
      for conjunctions, two for lexis, three for cohesive ties, and one for quality.
      There was good overall fit to the measurement model (item-trait chi-square =
      56.81, df = 48, p = 0.18) but the Person Separation Index was very low at 0.08
      mainly due to the small range of quality of essays in comparison to the
      difficulties of the writing devices (items). Students found that the three
      easiest writing devices used were remote cohesive ties, immediate cohesive ties
      and mediate cohesive ties. The three hardest writing devices used were temporal
      conjunctions, causal conjunctions and adversative conjunctions.

PMID- 19092229
TI  - Linking classical test theory and two-level hierarchical linear models.
AB  - This paper considers the link between classical test theory (CTT) and two-level
      hierarchical linear models (HLM). Conceptualizing that items are nested within
      subjects, we can reformulate the ANOVA classical test model as an HLM. In this
      HLM framework, item difficulty parameters are represented by the fixed effects,
      and subject's abilities are represented by the random effects. The population
      reliability of either the total or the mean score can be represented by a
      function of the random effects parameters and the number of items. For
      estimation, taking advantage of the balanced design nature of CTT, we can obtain
      explicit formulas for parameter estimates of both fixed and random effects in
      HLM. It reveals that the formula and the estimate derived from HLM exactly match
      those of CTT reliability, which are equivalent to Cronbach's coefficient alpha
      under the assumptions of essentially tau equivalent measures. Not only that, we
      can obtain most of the important quantities in CTT such as estimates of item
      difficulty, standard error of measurement, true score, and person ability in a
      single HLM model. Thus, the CTT model formulated by HLM framework provides a
      systematic approach on measurement analysis by CTT. For illustrative purpose, a
      small data set was analyzed using HLM software (Raudenbush, Bryk, Cheong, &
      Congdon, 2000). The results confirmed the theoretical link between CTT and HLM.

PMID- 19092230
TI  - Measuring self-complexity: a critical analysis of Linville's H statistic.
AB  - The paper argues that the most commonly used measure of self-complexity,
      Linville's H statistic, cannot measure this construct appropriately. It first
      examines the mathematical properties of H and its relationships with five related
      indices: the number of self-aspects, the overlap among self-aspects, the average
      inter-aspect correlation, the ratio of endorsement, and the HICLAS attribute
      class number. Then, a demonstration study using simulations is reported. Three
      conclusions are drawn. H and the HICLAS attribute class number are similar in the
      way they are calculated. Both indices are highly related to the number of self
      aspects, while their relationship to overlap is not monotonic. Overlap is
      affected by the ratio of endorsement and the average inter-aspect correlation but
      cannot represent the notion of redundancy among traits which directly determines
      Linville's H statistic. These conclusions are employed to explain the
      inconsistent findings relating self-complexity and adaptation and an alternative
      measurement approach is proposed.

PMID- 19092231
TI  - Measuring cynicism toward organizational change--one dimension or two?
AB  - Wanous, Reichers, and Austin's (2000) measure of cynicism about organizational
      change (CAOC) was subjected to validation and cross-validation procedures using
      data collected from two Australian public sector organizations. More specifically
      analyses were conducted to determine whether CAOC is best understood as a single
      dimensional or a two dimensional construct. The results of confirmatory factor
      analysis suggest that neither a one dimensional nor a two dimensional measurement
      model provided a satisfactory fit to the data. However, removal of two of the
      original eight items resulted in a two dimensional model, with three items in
      each dimension, that provided a reasonable fit to the data. Practical
      implications and directions for future research are discussed.

PMID- 19092232
TI  - Assessment of differential item functioning.
AB  - This study addresses several important issues in assessment of differential item
      functioning (DIF). It starts with the definition of DIF, effectiveness of using
      item fit statistics to detect DIF, and linear modeling of DIF in dichotomous
      items, polytomous items, facets, and testlet-based items. Because a common metric
      over groups of test-takers is a prerequisite in DIF assessment, this study
      reviews three such methods of establishing a common metric: the equal-mean
      difficulty method, the all-other-item method, and the constant-item (CI) method.
      A small simulation demonstrates the superiority of the CI method over the others.
      As the CI method relies on a correct specification of DIF-free items to serve as
      anchors, a method of identifying such items is recommended and its effectiveness
      is illustrated through a simulation. Finally, this study discusses how to assess
      practical significance of DIF at both item and test levels.

PMID- 19092233
TI  - In vitro differentiation of human cord blood-derived unrestricted somatic stem
      cells into hepatocyte-like cells on poly(epsilon-caprolactone) nanofiber
      scaffolds.
AB  - Tissue engineering of implantable cellular constructs is an emerging cellular
      therapy for hepatic disease. In this study, we tested the ability of poly(epsilon
      caprolactone) (PCL) nanofiber scaffold to support and maintain hepatic
      differentiation of human cord blood-derived unrestricted somatic stem cells
      (USSCs) in vitro. USSCs, self-renewing pluripotent cells, were isolated from
      human cord blood. The electrospun PCL nanofiber porous scaffold was constructed
      of uniform, randomly oriented nanofibers. USSCs were seeded onto PCL nanofiber
      scaffolds, and were induced to differentiate into hepatogenic lineages by
      culturing with differentiation factors for 6 weeks. RT-PCR analysis of endoderm
      and hepatic-specific gene expression, immunohistochemical detection of
      cytokeratin 18 (CK-18), alpha-fetoprotein, albumin, glycogen storage and
      indocyanine green uptake confirmed the differentiation of USSCs into endoderm and
      hepatocyte-like cells. In the present study, we show that hepatocyte-like cells
      differentiated from USSCs on the PCL nanofiber scaffold can be candidate for
      tissue engineering and cell therapy of hepatic tissues.

PMID- 19092234
TI  - Preserving oxygenation during walking in severe chronic obstructive pulmonary
      disease: noninvasive ventilation versus oxygen therapy.
AB  - BACKGROUND: Physical activity is known to cause significant deoxygenation in
      patients with severe chronic obstructive pulmonary disease (COPD). Although
      noninvasive positive pressure ventilation (NPPV) has been shown to improve
      oxygenation and physical activity in these patients, no practical approach for
      the application of NPPV during walking has yet been established. OBJECTIVE: To
      elucidate the most effective approach to preserving oxygenation during walking in
      patients with severe COPD receiving long-term NPPV. METHODS: Three 12-min walking
      tests were performed in a randomized cross-over design on 3 consecutive days,
      comparing the usual and double dosages of oxygen versus NPPV plus the usual
      dosage of oxygen. The ventilator and oxygen tank were placed in a backpack.
      RESULTS: Eleven patients (FEV(1) 26 +/- 9% predicted) completed the study, while
      8 patients refused to walk with NPPV, due to the weight of the ventilatory device
      (7.3 kg with NPPV vs. 3.1 kg without). PaO(2) changes during walking differed [p
      = 0.01, repeated-measures (RM)-ANOVA], whereas dyspnea was unchanged. The
      difference in PaO(2) change was 14.0 +/- 16.6 mm Hg (unadjusted p = 0.0036,
      critical level = 0.017, RM-ANOVA) in favor of NPPV compared to the usual dosage
      of oxygen. Changes in FEV(1), tidal volume and inspiratory impedance were in
      favor of NPPV-aided exercise (all p < 0.05, RM-ANOVA). Walking distance was
      reduced under NPPV (555 +/- 227 m) compared to the usual (619 +/- 210 m) and
      double (622 +/- 215 m) dosages of oxygen (p = 0.024, RM-ANOVA). CONCLUSIONS: NPPV
      plus supplemental oxygen, but not oxygen alone, preserves oxygenation during
      walking in patients with severe COPD. However, dyspnea and walking distance were
      not improved due to the burden of carrying the heavy ventilatory equipment in a
      backpack.

PMID- 19092235
TI  - Increased insulin sensitivity by metformin enhances intense-pulsed-light-assisted
      hair removal in patients with polycystic ovary syndrome.
AB  - BACKGROUND: Polycystic ovary syndrome (PCOS) is an insulin-resistant state with
      hirsutism as a common manifestation. OBJECTIVE: We hypothesized that treatment
      with metformin would improve the cosmetic effects of intense pulsed light (IPL)
      therapy for hair removal in PCOS patients. METHODS: In a prospective randomized
      controlled trial, 70 PCOS patients randomly received metformin (1,500 mg daily) +
      IPL therapy or IPL therapy alone for 5 IPL sessions during a 6-month period,
      followed by an additional 6 months of observation. Hirsutism score, homeostasis
      model assessment for insulin resistance (HOMA-IR), free androgen index (FAI) and
      patient satisfaction were evaluated at every visit. RESULTS: Fifty-two patients
      finished the study. Hirsutism was significantly better controlled in the
      metformin group (p = 0.009). Patient satisfaction was significantly better in the
      metformin group at the end of the observation period (52.9 vs. 34.1%, p = 0.019).
      HOMA-IR and FAI scores improved after metformin + IPL treatment (p < 0.05).
      CONCLUSION: Adding metformin to IPL in women with PCOS results in a significant
      improvement in insulin sensitivity and hirsutism.

PMID- 19092236
TI  - Induced sputum in interstitial lung diseases: novel insights in the diagnosis,
      evaluation and research.
AB  - The search for noninvasive procedures of retrieving cells and soluble material
      from the lung has gained momentum over the past few years. Induced sputum (IS) by
      inhalation of hypertonic saline solution is a noninvasive technique used to
      collect cellular and soluble material from lung airways. During the past decade,
      this method has been widely used to assess airway inflammation in asthma and
      chronic obstructive disease, since it produces reliable results and compares
      favorably to other invasive techniques, such as biopsy and bronchoalveolar lavage
      fluid. However, recent attention has been paid to its efficacy in the evaluation
      of interstitial lung diseases. Recent research in this area clearly showed that
      IS analysis could give extensive information regarding the inflammation in
      pulmonary sarcoidosis, such as the lymphocytic cell count, the CD4+/CD8+ ratio
      and the Th1 immunologic response. The CD4+/CD8+ ratio recovered from lymphocytes
      from IS is as useful as the same value retrieved from examination of lymphocytes
      recovered from bronchoalveolar lavage fluid for clinical use. The above findings
      suggest that integrating IS procedure in the diagnosis, evaluation, follow-up and
      research in patients with pulmonary sarcoidosis is necessary. Besides
      sarcoidosis, the review of the current literature in other interstitial lung
      diseases showed that IS could provide us with useful information regarding
      inflammatory molecules, but cannot fully replace more invasive techniques. This
      review analyzes the applications of IS in the assessment of fibrotic and
      granulomatous diseases such as sarcoidosis and extrinsic allergic alveolitis,
      idiopathic pulmonary fibrosis, connective tissue disorders, occupational lung
      diseases and other systemic diseases.

PMID- 19092237
TI  - Safety and outcome after thrombolysis in stroke patients with mild symptoms.
AB  - BACKGROUND: Thrombolytic therapy is frequently withheld in patients with minor
      stroke symptoms. However, recent studies demonstrate that a substantial
      proportion of these patients dies or remains permanently disabled because of
      underestimation of symptom severity at baseline or secondary deterioration. We
      aimed to assess the safety and outcome of thrombolysis therapy in patients with
      minor but disabling stroke symptoms. METHODS: 32 patients presenting with mild
      symptoms were treated with intravenous recombinant tissue-type plasminogen
      activator between April 2006 and April 2008. Data were extracted from a
      prospectively collected database. Baseline demographic data, and clinical,
      laboratory and imaging findings were analyzed. Outcome was assessed using the
      modified Rankin Scale (mRS) score at 3 months and was dichotomized into favorable
      (mRS 0-1) versus unfavorable (mRS 2-6). RESULTS: In the majority of patients, the
      left hemisphere was affected, with aphasia representing the most common symptom
      leading to treatment decision. The frequency of perfusion lesion (46%) and vessel
      occlusion (35%) at baseline was high but had no effect on the outcome at 3 months
      in our series of treated patients. Outcome was favorable in 94% of patients, and
      47% recovered without any persisting symptom. Only one asymptomatic and no
      symptomatic hemorrhage was observed. CONCLUSION: Our data support current
      guidelines and international licenses which give no lower National Institutes of
      Health Stroke Scale (NIHSS) limit for intravenous thrombolysis (IVT). Considering
      the accumulating evidence that the natural course in patients with mild symptoms
      is not as favorable as often assumed and taking the low risk of bleeding in those
      patients into account, patients with mild but disabling symptoms should be
      treated with IVT regardless of their baseline NIHSS score.

PMID- 19092238
TI  - Pragmatic management of hyperglycaemia in acute ischaemic stroke: safety and
      feasibility of intensive intravenous insulin treatment.
AB  - BACKGROUND: In patients with acute ischaemic stroke, hyperglycaemia has been
      retrospectively associated with negative outcome. There is an ongoing discussion
      as to which treatment algorithm, if any, provides the most effective prospective
      intervention. Here we test the safety and feasibility of an intravenous insulin
      only infusion protocol designed for pragmatic routine clinical use. METHODS: 40
      ischaemic stroke patients with onset <24 h ago, admitted to our stroke unit, were
      randomized either to the study regimen (50 IU insulin in 50 ml 0.9% saline
      solution applied intravenously via a perfusor pump), with the aim of reaching and
      maintaining blood glucose levels between 4.44 mmol/l (80 mg/dl) and 6.11 mmol/l
      (110 mg/dl), or were treated with insulin subcutaneously if concentrations were
      above 11.10 mmol/l (200 mg/dl). Treatment was continued for 5 days. Primary
      outcome was the number of hypoglycaemic (<3.33 mmol/l; <60 mg/dl) and severe
      hyperglycaemic (>16.65 mmol/l; >300 mg/dl) events. RESULTS: Hypoglycaemic events
      were significantly more common in patients treated intensively (total n = 25;
      incidence rate ratio, IRR = 5.3; 95% CI = 1.2-22.4; p < 0.05). Symptomatic events
      were rare (total n = 5). Severe hyperglycaemia was associated with conventional
      treatment (IRR = 4.9; 95% CI = 1.5-15.9; p < 0.05). Though those treated
      intensively attained near-normoglycaemic levels quicker and had significantly
      lower blood glucose levels over the study period (6.49 +/- 2.19 mmol/l vs. 8.01
      +/- 3.06 mmol/l; 95% CI = -1.78 to -1.28, p < 0.0005), treatment imposes
      considerable strain on both patients and caregivers. CONCLUSIONS: The intensive
      intravenous insulin infusion protocol effectively lowers blood glucose levels
      with an increased risk of manageable hypoglycaemic events. However, a highly
      motivated and trained staff seems essential, limiting feasibility outside of
      specialty care settings.

PMID- 19092239
TI  - Common variants in interleukin-1-Beta gene are associated with intracranial
      hemorrhage and susceptibility to brain arteriovenous malformation.
AB  - BACKGROUND: Polymorphisms in the proinflammatory cytokine interleukin (IL)-1beta
      gene have been associated with systemic atherogenesis, thrombosis and rupture.
      The aim of this study was to investigate associations between single nucleotide
      polymorphisms (SNPs) in IL-1beta and intracranial hemorrhage (ICH) in the natural
      course of brain arteriovenous malformation (BAVM) patients. METHOD: Two IL-1beta
      promoter SNPs (-511C-->T, -31T-->C) and 1 synonymous coding SNP in exon 5 at
      +3953C-->T (Phe) were genotyped in 410 BAVM patients. We performed a survival
      analysis of time to subsequent ICH, censoring cases at first treatment, death or
      last follow-up. A Cox regression analysis was performed to obtain hazard ratios
      (HRs) for genotypes adjusted for age, sex, Caucasian race/ethnicity and
      hemorrhagic presentation. RESULTS: Subjects with the -31 CC genotype (HR = 2.7;
      95% CI 1.1-6.6; p = 0.029) or the -511 TT genotype (HR = 2.6; 95% CI 1.1-6.5; p =
      0.039) had a greater risk of subsequent ICH compared with reference genotypes,
      adjusting for covariates. The +3953C-->T SNP was not significantly associated
      with an increased ICH risk (p = 0.22). The IL-1beta promoter polymorphisms were
      also associated with BAVM susceptibility among a subset of 235 BAVM cases and 255
      healthy controls of Caucasian race/ethnicity (p < 0.001). CONCLUSION: IL-1beta
      promoter polymorphisms were associated with an increased risk of ICH in BAVM
      clinical course and with BAVM susceptibility. These results suggest that
      inflammatory pathways, including the IL-1beta cytokine, may play an important
      role in ICH.

PMID- 19092241
TI  - Pulse pressure--independent predictor of poor early outcome and mortality
      following ischemic stroke.
AB  - BACKGROUND: Pulse pressure (PP) in acute stroke may be related to the outcome.
      The link between PP in the first week following ischemic stroke and early outcome
      was assessed. METHODS: We calculated mean PPs during the first 7 days after
      stroke onset in 1,677 patients. Poor outcome at hospital discharge was defined as
      a modified Rankin scale score of 3 or more points or death. Logistic regression
      was developed to evaluate PP as an independent predictor of early outcome.
      RESULTS: For patients with poor outcomes the mean PP during the first week was
      higher than that for patients with non-poor outcomes. A logistic regression model
      confirmed that elevated mean PP was independently associated with poor outcome at
      discharge and 30-day mortality. CONCLUSION: Elevated PP during the acute phase of
      ischemic stroke is an independent predictor of poor early outcome at hospital
      discharge and 30-day mortality.

PMID- 19092240
TI  - Comparison of two headgear systems for sleep apnea treatment of stroke patients.
AB  - BACKGROUND: Obstructive sleep apnea is a very common condition after stroke, and
      it predicts poor outcomes. Unfortunately, stroke patients often do not tolerate
      continuous positive airway pressure. We hypothesized that a 1-piece head frame
      headgear would be easier and quicker to use than a traditional strap headgear.
      METHODS: A convenience sample of ischemic stroke patients was taught to use 2
      different headgear systems, a head frame and straps. Subjects were timed while
      putting on and taking off the 2 headgears, and they were queried about their ease
      of use. RESULTS: All the 30 enrolled subjects found the head frame to be easier
      to apply and to remove than the straps. The patients took longer to put on (p <
      0.01) and to remove (p < 0.01) the straps than the head frame. CONCLUSIONS:
      Headgear selection should be considered when fitting a stroke patient with a
      continuous positive airway pressure mask.

PMID- 19092242
TI  - The effect of acute hypoxemia on coronary arterial dimensions in patients with
      coronary artery disease.
AB  - OBJECTIVES: To assess the influence of acute hypoxemia on the dimensions of
      diseased and nondiseased coronary arterial segments in humans. METHODS: In 18
      subjects (age 53 +/- 8 years) with known or suspected coronary artery disease,
      quantitative coronary angiography was performed before and after being randomly
      assigned to breathing (1) an inspired oxygen concentration (fraction of inspired
      oxygen, FIO2) of 21% (room air, RA) for 20 min (n = 4, controls) or (2) an FIO2
      of 15 and 10% for 10 min each (corresponding to altitudes of 2,500 and 5,500 m,
      respectively; n = 14). RESULTS: In the control subjects, no hemodynamic,
      oximetric or angiographic variable changed. In the 14 study subjects, the
      arterial partial pressure of oxygen averaged 85 +/- 13 mm Hg on RA, 65 +/- 15 mm
      Hg on 15% FIO2 and 44 +/- 13 mm Hg on 10% FIO2. Average arterial segment diameter
      was 2.52 +/- 0.63 mm on RA, 2.55 +/- 0.62 mm on 15% FIO2 (not significant vs. RA)
      and 2.66 +/- 0.66 mm on 10% FIO2 (p < 0.001 vs. RA). The increase in coronary
      arterial diameter with 10% FIO2 occurred only in normal segments (2.74 +/- 0.64
      vs. 2.97 +/- 0.64 mm; p < 0.001), but not in diseased segments (2.34 +/- 0.57 vs.
      2.38 +/- 0.55 mm; not significant). CONCLUSIONS: In humans, severe hypoxemia
      induces vasodilation of angiographically normal coronary arterial segments,
      whereas it causes no change in diseased segments.

PMID- 19092243
TI  - Treatment of gastroparesis: an update.
AB  - Gastroparesis is a chronic disorder of gastric motility that is characterized by
      delayed emptying of either solids or liquids from the stomach in the absence of
      any mechanical obstruction. Nausea, vomiting, early satiety and bloating are some
      of the manifestations of gastroparesis. Idiopathic, diabetes mellitus and
      postsurgical states account for the majority of cases. Gastroparesis is a
      difficult condition to treat. Prokinetic drugs like metoclopramide and
      erythromycin form the mainstay of therapy but are less than ideal. Some patients
      may benefit from endoscopic botolinium toxin injection. Gastric electrical
      stimulation, though promising, is not ready for prime time yet.

PMID- 19092244
TI  - Evaluation of crofelemer in the treatment of diarrhea-predominant irritable bowel
      syndrome patients.
AB  - BACKGROUND: Crofelemer improves bowel function in several conditions
      characterized by states of prominent secretory diarrhea. AIM: This double-blind,
      randomized, placebo-controlled trial evaluated the effects of 3 dose levels of
      crofelemer in patients with diarrhea-predominant irritable bowel syndrome (D
      IBS). METHODS: Male and female patients were randomly assigned to receive
      crofelemer 125, 250 or 500 mg or placebo twice daily for 12 weeks. The primary
      efficacy measure was a responder for improvement in stool consistency. In
      addition, abdominal pain- and discomfort-free days, pain and discomfort scores as
      well as other bowel function parameters (such as stool frequency and consistency,
      urgency, bloating) were evaluated. RESULTS: Two hundred and forty-two D-IBS
      patients were randomized. Crofelemer did not produce significant improvement in
      stool consistency (primary endpoint), stool frequency, urgency or adequate
      relief. However, female D-IBS patients showed improvement in the proportion of
      pain- and discomfort-free days during treatment with 500 mg crofelemer: month 1
      (crofelemer vs. placebo: 17.7 vs. 10.2%, p = 0.098); month 2 (23.5 vs. 13.3%, p =
      0.076); month 3 (26.1 vs. 10.6%, p = 0.0076). No benefit was seen in male D-IBS
      patients. Crofelemer was well tolerated. CONCLUSIONS: Crofelelmer did not produce
      benefit on bowel function; an increase in the number of pain- and discomfort-free
      days in female D-IBS patients was seen. Further studies with crofelemer are
      warranted to evaluate it as a potential visceral analgesic.

PMID- 19092245
TI  - Nurse-administered propofol sedation safety further confirmed - but can we really
      allow our patients to drive afterwards?

PMID- 19092246
TI  - Safety and driving ability following low-dose propofol sedation.
AB  - BACKGROUND AND AIM: Automobile driving is prohibited after midazolam sedation
      because of the slow recovery of psychomotor function. This study prospectively
      assessed the safety of low-dose propofol sedation (study 1) and compared driving
      ability following propofol and midazolam sedation (study 2). METHODS: Study 1: We
      prospectively investigated bolus injection of a low-dose of propofol (40-80 mg
      for <70 years and 30 mg for >or=70 years) for diagnostic
      esophagogastroduodenoscopy (EGD). Respiratory depression, time to full recovery,
      and overall patient satisfaction were evaluated and blood concentrations of
      propofol were measured. Study 2: A subset of subjects undergoing diagnostic EGD
      were randomized to receive 40 mg of propofol (n = 30), 4 mg of midazolam (n = 30)
      or no sedation controls (n = 20), and the residual effects of each drug were
      tested using a driving simulator. The primary outcome measure was driving
      ability. The second outcome measures were overall patient satisfaction and
      complications. RESULTS: Study 1: Only 1.1% of 12,031 healthy subjects developed
      transient oxygen desaturation. Full recovery was present in 97.5% 30 min after
      the procedure; 99.8% were willing to repeat the same procedure. The blood levels
      of propofol (40-80 mg) at 60 min were <100 ng/ml. Study 2: Driving ability
      recovered to the basal level within 60 min of propofol administration but not
      with 120 min with midazolam. There were no complications; overall patient
      satisfaction was similar between propofol and midazolam (8.9 vs. 8.5, p = 0.34).
      CONCLUSION: Low-dose propofol sedation was safe and recovery including driving
      ability was with 60 min.

PMID- 19092248
TI  - Controlled-release oxycodone and pregabalin in the treatment of neuropathic pain:
      results of a multicenter Italian study.
AB  - AIMS: The aim of our study was to compare the efficacy, safety, and quality of
      life of combination therapy with controlled-release (CR) oxycodone plus
      pregabalin versus monotherapy with either CR oxycodone or pregabalin in patients
      with neuropathic pain. MATERIALS AND METHODS: Patients with moderate to severe
      neuropathic pain, despite the use of various pharmacologic treatments prior to
      study entry, were enrolled (n = 409) and treated with CR oxycodone plus
      pregabalin (n = 169), CR oxycodone (n = 106), and pregabalin (n = 134). Pain
      intensity was rated on an 11-point numerical rating scale (NRS). RESULTS: The
      combination of CR oxycodone plus pregabalin and CR oxycodone monotherapy were
      both more effective for alleviating neuropathic pain than pregabalin monotherapy
      (reduction in NRS value: 80, 76, and 46%, respectively; p </= 0.003).
      Significantly greater improvements from baseline in quality of life were reported
      with combination therapy than with monotherapy (p = 0.0009). At the end of
      treatment, the majority (91.2%) of patients receiving CR oxycodone plus
      pregabalin found that the treatment had been 'effective' or 'very effective'.
      Combination therapy also allowed a dose reduction of both agents (22% for CR
      oxycodone and 51% for pregabalin) compared with the dosages of the respective
      monotherapies. Combination therapy had a superior safety profile compared with
      pregabalin monotherapy. CONCLUSIONS: The combination of CR oxycodone plus
      pregabalin may represent a valuable addition to the existing pharmacotherapy for
      neuropathic pain and warrants further investigation.

PMID- 19092249
TI  - 'The Adventure': Charles-Ferdinand Ramuz's extraordinary stroke diary.
AB  - The famous Swiss writer Charles-Ferdinand Ramuz suffered a stroke at 65 years,
      which he called 'the adventure' or 'the accident'. He developed language
      disturbances suggesting crossed aphasia in a right hander with left hemiparesis.
      This uncommon pattern allowed him to continue to write his diary and to report
      his disturbances, with a unique depth and precision, especially for cognitive
      emotional changes. Language and motor dysfunction recovered within a few weeks,
      but Ramuz complained of persisting emotional flattening alternating with
      irritability, fatigue, depression, anxiety, and concentration difficulty, which
      gave him the feeling to have become another person and to be inhabited by a
      stranger, whom he compared with devils. Ramuz fought several months to resume his
      literary activity, having the impression to have lost inspiration and creativity.
      However, the novels he wrote less than 6 months after stroke show no stylistic
      changes and have been found to be of the same quality as his previous production.
      Ramuz even 'used' his stroke experience in his work, in particular in a novel
      depicting an old man who has a stroke and dies of it. Ramuz's diary, with his own
      daily description of stroke features and consequences during acute and recovery
      phases, is a unique document in a writer of his importance, and provides
      invaluable information on subjective emotional and cognitive experience of
      stroke.

PMID- 19092250
TI  - Clinical characteristics and outcomes of the meningitides in systemic lupus
      erythematosus.
AB  - BACKGROUND: The meningitides are rare but well-identified complications in
      patients with systemic lupus erythematosus (SLE). AIMS: To determine the clinical
      characteristics, risk factors, prevalence and outcomes of the meningitides
      (septic and aseptic) in patients with SLE. PATIENTS AND METHODS: From January
      1988 to December 2006, we identified patients with SLE and septic or aseptic
      meningitis. RESULTS: We identified 25 episodes of meningitis in 23 patients with
      SLE, from a total of 1,411 SLE patients (1.63%); in 15 out of 25 episodes, a
      microorganism was identified. Mycobacterium tuberculosis, Listeria monocytogenes
      and Criptococcus neoformans represented the main microorganisms. In 10 episodes,
      aseptic meningitis was diagnosed. Lymphopenia, steroid use, chronic damage and
      systemic activity of SLE were frequent in both kinds of meningitis. Although the
      clinical presentation did not differ significantly, patients with septic
      meningitis had more residual neurological deficits (p = 0.04). CONCLUSIONS:
      Meningitis was observed in about 1.6% of the patients with SLE; in 40% of the
      cases, no microorganism could be isolated. A residual neurological deficit was
      more common in patients with septic meningitis.

PMID- 19092251
TI  - Effect of cabergoline on parkinsonian tremor assessed by long-term actigraphy.
AB  - BACKGROUND: Tremor is one of the cardinal symptoms in Parkinson's disease, but
      only few clinical studies have focussed on its therapy as the primary endpoint.
      One reason is the substantial fluctuation of tremor severity over time, which is
      difficult to capture and may render momentary clinical assessments unreliable.
      METHODS: We evaluated the usefulness of a novel wrist-worn actigraph allowing
      long-term recordings of tremor in a pilot study, in which we assessed the
      therapeutic effect of cabergoline on tremor in 10 patients with tremor-dominant
      Parkinson's disease. Clinical data were obtained by using the Unified Parkinson's
      Disease Rating Scale (UPDRS Part III, item 20) and simultaneously a patient's
      tremor diary. RESULTS: We found a significant reduction in UPDRS motor and tremor
      scores, in tremor duration and tremor amplitude by actigraphy and diaries.
      Furthermore, we found significant correlations between actigraphy measurements
      and patient ratings of tremor intensity and occurrence in diaries. CONCLUSION:
      Long-term actigraphy is a reliable method to assess tremor occurrence and
      severity and may be used to document antitremor effects in clinical studies.

PMID- 19092252
TI  - Novel KRIT1 mutation and no molecular evidence of anticipation in a family with
      cerebral and spinal cavernous malformations.
AB  - BACKGROUND: Cerebral cavernous malformations (CCM) are vascular brain anomalies
      which can result in a variety of neurological symptoms. Familial CCM is inherited
      as an autosomal-dominant trait. There is one study in the literature which
      reports statistical evidence for anticipation in familial CCM. METHODS: We
      reevaluated the clinical course of the disease and performed molecular analyses
      in a previously described three-generation CCM family with apparent anticipation.
      RESULTS: Disease started at a younger age in each generation, strongly suggesting
      anticipation. The patient in generation I showed no clinical symptoms by the age
      of 68, whereas his son became wheelchair-bound at the age of 43 due to an
      intramedullary cavernous malformation at the thoracolumbar transition of the
      spinal cord. The patient in generation III had a pons hemorrhage at the age of 11
      due to a large brainstem cavernoma. The hemorrhage caused facial palsy and
      hemiparesis, persisting as Millard-Gubler syndrome. Sequencing of KRIT1
      identified a novel frameshift mutation in exon 15 (c.1561delC or p.Leu551X) which
      cosegregated with the phenotype. Flow-FISH analysis of granulocyte and lymphocyte
      telomere length showed that telomeres were longest in the youngest affected
      family member. CONCLUSIONS: We could not find any evidence for either of the two
      currently known molecular mechanisms for genetic anticipation (i.e., expansion of
      repetitive DNA elements or progressive telomere shortening) in this family.
      However, the family presented here raises the important question whether
      surveillance of CCM families with gradient-echo MRI should not only include the
      cerebrum, but the spinal cord as well.

PMID- 19092253
TI  - Cognitive impairment and seizures in patients with lacunar strokes.
AB  - BACKGROUND: Lacunar infarcts and white matter changes have been linked to
      cognitive impairment. Patients with lacunar strokes can also develop seizures,
      although the relationship between the two remains unclear. The present study
      investigates whether seizures in patients with lacunar infarcts are related to
      the strokes or to an underlying neurodegenerative disorder leading to cognitive
      impairment. METHODS: The demographic features, vascular risk factors and scores
      on the National Institutes of Health Stroke Scale (NIHSS) on admission for the
      stroke and on the modified Rankin scale on discharge, as well as on the Mini
      Mental State Examination (MMSE), were determined in patients with a lacunar
      stroke. They were compared between 44 patients with and 248 without subsequent
      seizures. RESULTS: Patients with seizures had a lower main NIHSS score (p =
      0.00133) and a more severe MMSE score (p < 0.001). They remained significantly
      more dependent (p = 0.019) after hospital discharge. Smoking, as a vascular risk
      factor, appeared to occur less frequently in seizure patients (p = 0.039). On
      logistic regression analysis, only NIHSS and MMSE scores remained independent
      variables. CONCLUSIONS: Seizure occurrence in patients with a lacunar infarct is
      not related to the severity of the stroke but rather to the degree of cognitive
      impairment. The present study suggests that the seizures are not due to lacunar
      infarcts but are more probably the expression of an underlying neurodegenerative
      process that is also responsible for the mental deterioration.

PMID- 19092254
TI  - Spinal hamartoma with severe kyphoscoliosis--a rare case of spinal mass in a
      fetus.
AB  - Spinal hamartomas are rare lesions consisting of disorganized ecto- and
      mesodermal tissues of the spinal region. While postnatal identification of spinal
      hamartomas has been reported, a literature search did not reveal any published
      reports of prenatal identification of spinal hamartomas. Here we report a 46,XX
      fetus who presented at 20 weeks' gestation with a lower thoracic and lumbar
      kyphoscoliosis, suspected spina bifida, and amniotic fluid alpha-fetoprotein
      (AFP) levels within the normal range. Interestingly, autopsy at 22 weeks revealed
      a lumbosacral spinal hamartoma with kyphoscoliosis. We discuss the differential
      diagnosis for such spinal masses which includes congenital tumors and spinal
      dysraphism. This case illustrates that spinal hamartomas should be considered as
      part of the prenatal differential diagnosis of spinal dysraphisms, especially in
      the presence of normal AFP levels.

PMID- 19092256
TI  - Noncanalized horns of uterus didelphys with prolapse: a unique case in a young
      woman.
AB  - The authors report the unique case of a 20-year-old patient with prolapsed uterus
      didelphys with noncanalized horns, who complained of primary amenorrhea. Clinical
      examination revealed a rudimentary noncanalized cervix with a third degree
      prolapse and no palpable uterus. A small prolapsing remnant of a uterus didelphys
      with 2 noncanalized uterine horns was excised by laparotomy. Ultrastructural
      examination of subepithelial cervical connective tissue revealed collagen of
      normal structure, but of low concentration. The etiologies of both the Mullerian
      ducts anomalies and the genital prolapse are probably multifactorial. Low
      collagen concentration indicates a constitutional tissue weakness contributing to
      the development of genital prolapse.

PMID- 19092255
TI  - To treat or not to treat euthyroid autoimmune disorder during pregnancy?
AB  - BACKGROUND: Subclinical autoimmune hypothyroidism during pregnancy is associated
      with an increased risk of miscarriage and has a deleterious effect on fetal
      development. The aim of this study was to evaluate a screening and treatment
      strategy of subclinical hypothyroidism, and to establish normal ranges of thyroid
      stimulating hormone (TSH) and thyroxine (T(4)) during pregnancy. METHODS: A
      retrospective study was carried out on 784 consecutive files of pregnant women;
      the files were systematically searched for thyroid function and antithyroid
      antibodies in order to determine the effect and the prevalence of anti-thyroid
      peroxidase antibodies (TPO-Ab) during pregnancy, and to evaluate treatment with
      levothyroxin (LT(4)) in TPO-Ab carriers. RESULTS: Among the 75 TPO-Ab-positive
      patients, 42 received LT(4) treatment during pregnancy. Although the range of TSH
      serum levels was wide, the mean TSH level was significantly higher in TPO-Ab
      positive women (3 vs. 1 mIU/l, p < 0.01). No significant difference in the
      obstetrical complications rate was observed between TPO-Ab-positive and TPO-Ab
      negative populations. CONCLUSIONS: Our study provides information on normal
      ranges of serum TSH and free T(4) for Belgian pregnant women receiving iodide
      supplementation. Based on our results, we suggest supplementation of TPO-Ab
      positive pregnant women with 50 microg/day of LT(4), unless their TSH levels are
      lower than 1 mIU/l, to avoid the risk of hypothyroidism during pregnancy.

PMID- 19092257
TI  - The effect of N-acetylcysteine on proteinuria and markers of tubular injury in
      non-diabetic patients with chronic kidney disease. A placebo-controlled,
      randomized, open, cross-over study.
AB  - BACKGROUND: Inhibition of the renin-angiotensin-aldosterone system with
      angiotensin-converting enzyme inhibitors (ACEI) and/or angiotensin II subtype 1
      receptor antagonists (ARB) constitutes a strategy in the management of patients
      with chronic kidney disease. There is still no optimal therapy which can stop the
      progression of chronic kidney disease. Antioxidants such as N-acetylcysteine
      (NAC) have been reported as a promising strategy in this field. METHODS: In a
      placebo-controlled, randomized, open, 2-period cross-over study, we evaluated the
      influence of NAC (1,200 mg/day) added to renin-angiotensin-aldosterone system
      blockade on proteinuria and surrogate markers of tubular injury and renal
      fibrosis in 20 non-diabetic patients with proteinuria (0.4-6.36 g/24 h) with
      normal or decreased kidney function (estimated glomerular filtration rate 61-163
      ml/min). Subjects entered the 8-week run-in period during which the therapy using
      ACEI and/or ARB was established with blood pressure below 130/80 mm Hg. Next,
      patients were randomly assigned to 1 of 2 treatment sequences:
      NAC/washout/placebo or placebo/washout/NAC. Clinical evaluation and laboratory
      tests were performed at the randomization point and after each period of the
      study. RESULTS: No significant changes in laboratory tests were observed.
      CONCLUSION: NAC had no effect on proteinuria, surrogate markers of tubular injury
      or renal fibrosis in non-diabetic patients with chronic kidney disease.

PMID- 19092258
TI  - Historical aspects.

PMID- 19092259
TI  - Techniques.

PMID- 19092260
TI  - B cell neoplasms.

PMID- 19092261
TI  - T cell neoplasms.

PMID- 19092262
TI  - Hodgkin lymphoma.

PMID- 19092263
TI  - Histiocytic and dendritic neoplasms.

PMID- 19092264
TI  - Extranodal lymphomas.

PMID- 19092265
TI  - Lymphoma look-alike.

PMID- 19092266
TI  - Hepatocellular carcinoma 2009 and beyond: from the surveillance to molecular
      targeted therapy.
AB  - Hepatocellular carcinoma (HCC) is a malignant tumor which is becoming more
      prevalent worldwide. Patients at high risk of developing HCC, namely hepatitis B-
      and C-related liver cirrhosis patients, should be entered into surveillance
      programs, which should be performed using both ultrasonography and 3 tumor
      markers (AFP, PIVKA-II, AFP-L3). The surveillance interval needs to be shortened
      for patients at higher risk of HCC. Therefore, super-high-risk patients should be
      screened at 3- to 4-month intervals based on their risk of developing HCC.
      Sonazoid-enhanced US is extremely useful to characterize hepatic tumors when
      compared with multidetector-row computed tomography (MDCT). Moreover, Sonazoid
      enhanced US with defect reperfusion imaging is a breakthrough approach in the
      treatment of HCC. This technique will markedly change the therapeutic strategy
      for liver cancer. Furthermore, diagnostic capability using the new imaging
      technique Gd-EOB-DTPA MRI is promising. A reduced uptake (low intensity) in the
      hepatobiliary phase of Gd-EOB-DTPA MRI strongly suggests HCC (including early
      stage HCC) or a high-grade dysplastic nodule with high malignant potential.
      Empirically, intrahepatic arterial infusion chemotherapy using implanted
      reservoir port is known to be effective for advanced HCC with vascular invasion;
      however, no randomized study exists to prove its efficacy. Further controlled
      study is necessary to establish this treatment option as a standard of care in a
      treatment algorithm for HCC. In contrast, sorafenib was established as the first
      choice of treatment as a standard of care in advanced HCC patients with preserved
      liver function and vascular invasion/extrahepatic spread. Furthermore, global
      clinical trials are now ongoing using sorafenib as an adjuvant setting after
      resection, ablation or TACE. Efficacy of combined use of sorafenib with TACE or
      intra-arterial infusion chemotherapy is not clear. In order to clarify this issue
      a randomized clinical trial for intermediate and advanced HCC comparing sorafenib
      alone versus sorafenib combined with maintenance TACE/intra-arterial infusion
      chemotherapy and/or intra-arterial infusion chemotherapy is scheduled to be
      initiated in Japan in 2009. If positive results are obtained by these trials, its
      impact on treatment strategy for HCC will be drastically changed.

PMID- 19092267
TI  - Epidemiology of hepatocellular carcinoma in Japan and Korea. A review.
AB  - The worldwide burden of liver cancer has been estimated at 671,000 new cases for
      the year 2005. Hepatocellular carcinoma (HCC) accounts for between 85 and 90% of
      primary liver cancer and is one of the most frequent malignancies in Asia. In
      both Japan and Korea, the incidence exceeds 25 cases/100,000/year and ranks third
      in cancer deaths after stomach and lung cancer. In Korea the number of deaths
      from liver cancer increased from approximately 5,789 in 1983 to 9,966 in 1994,
      and then remained steady at 9,500/100,000 in 2003. In Japan the number of deaths
      from HCC increased until 2002, and then decreased to 34,089 in 2003, up to 15% of
      HCC cases are caused by hepatitis B virus (HBV) and approximately 80% by
      hepatitis C virus (HCV) infection; the corresponding figures in Korea are
      approximately 70 and approximately 20%. Recent clinical data have shown that
      interferon and lamivudine treatment is effective in preventing the occurrence of
      HCC attributed to HCV and HBV infection, respectively, and that an aggressive
      vaccination program against the latter reduces the incidence of HCC. With the
      enormous efforts of researchers devoted to basic and clinical studies, the
      incidence of HCC is expected, in the near future, to gradually decline in both
      countries.

PMID- 19092268
TI  - Experimental agents which inhibit hepatocarcinogenesis.
AB  - Hepatocellular carcinoma (HCC) is characteristically hypervascular, and therefore
      many antiangiogenic therapies are under clinical investigation. However, their
      therapeutic efficacies are still limited. While inhibition of angiogenesis
      results in tumor hypoxia and cell death, this may also activate a variety of
      hypoxia-induced cell growth and survival signals, which may promote HCC
      progression. Therefore, the simultaneous blockage of these signals may be
      essential in maximizing the efficiency of antiangiogenic therapies. Information
      regarding some of our experimental agents targeting these HCC signals is
      presented in this manuscript.

PMID- 19092269
TI  - Inhibitory function of interferon on hepatocarcinogenesis.
AB  - OBJECTIVE: We examined the growth-inhibitory effect and the mechanism of action
      of type I interferon (IFN) in human liver cancer cell lines in vitro and in vivo.
      METHODS: We examined the growth-inhibitory effect of 5 types of type I IFN
      preparations (e.g., pegylated, nonpegylated IFN-alpha, and IFN-beta) used for the
      treatment of chronic hepatitis C in 13 liver cancer cell lines in vitro. After
      liver cancer cells were transplanted into nude mice, various doses of IFN
      preparations were subcutaneously administered, and the antitumor effect was
      examined. RESULTS: The growth-inhibitory effect of each preparation was
      different, but IFN-beta expressed the strongest effects in vitro. Induction of an
      inhibition of cell cycle progression at the G(1), S or G(2)/M phase with or
      without apoptosis was the mechanism of action of IFN. IFN preparations induced a
      dose-dependent decrease in tumor volume and weight by inducing tumor cell
      apoptosis in vivo, and tumor growth was effectively suppressed even at the
      clinical dose for chronic hepatitis C treatment. The antitumor effect of
      pegylated IFN was significantly stronger than that of nonpegylated IFN.
      CONCLUSION: The data suggest potential clinical application of pegylated IFN for
      the prevention and treatment of hepatocellular carcinoma.

PMID- 19092270
TI  - Impact of interferon therapy after curative treatment of hepatocellular
      carcinoma.
AB  - Primary and secondary prevention of hepatocellular carcinoma (HCC) which has
      become endemic worldwide in recent years are the most important issues in
      reducing mortality of HCC patients. Among several compounds previously reported
      for secondary prevention, treatment with interferon (IFN) is widely applied and
      shows encouraging results. To date, there have been 8 published randomized
      control trials (RCTs) and 6 published non-RCTs on IFN therapy after curative
      treatment of HCCs. Positive results were shown in 6 of 8 RCTs and in all of 6 non
      RCT cohort studies regarding either recurrence rate or patient survival. The
      impact of IFN therapy after curative treatment of HCC can be summarized as
      follows: (1) HCC incidence of recurrence is reduced through viral clearance or
      long-term IFN treatment, even though HCV is not cleared. (2) Low-dose, long-term
      IFN (maintenance) therapy may suppress HCC recurrence through direct action of
      IFN on tumor cells. (3) Patient survival is improved through growth inhibition of
      recurrent tumors, as well as preservation of liver function. (4) According to the
      above 3 points, there is more chance to receive curative treatment in the IFN
      than the non-IFN group. (5) Pegylated IFN (PEG-IFN) may be more beneficial than
      non-PEG-IFN products since IFN concentration is maintained in the body at a high
      level, which is favorable for its action as a direct anticancer agent. (6) It may
      be concluded that IFN treatment after curative treatment of HCC is beneficial at
      least in HCV-related HCC, since it lowers recurrence and improves survival.

PMID- 19092271
TI  - Sonazoid-enhanced ultrasonography for diagnosis of hepatic malignancies:
      comparison with contrast-enhanced CT.
AB  - OBJECTIVE: The purpose of this study was to assess the usefulness of Sonazoid
      enhanced ultrasonography (US) in the diagnosis of hepatic malignancies in
      comparison with contrast-enhanced CT findings. METHODS: A total of 74 patients
      with 113 hepatic tumors having or highly suspected of having malignancies were
      enrolled. These hepatic nodules were diagnosed by typical findings of imaging
      such as contrast-enhanced CT, dynamic MRI or Sonazoid-enhanced US, tumor markers
      and histological examinations after surgical resection or biopsy. RESULTS: 108
      nodules were diagnosed as malignant tumors (hepatocellular carcinoma: n = 90;
      metastasis: n = 16; intrahepatic cholangiocarcinoma: n = 2) and the remaining
      five tumors were diagnosed as benign tumors (dysplastic nodules: n = 5). Sonazoid
      enhanced US correctly depicted the presence or absence of tumors in 74 patients,
      with a sensitivity of 95.4%, an accuracy of 94.7%, and a positive predictive rate
      of 99%. Contrast-enhanced CT depicted the malignancies with a sensitivity of
      85.2%, an accuracy of 82.3%, and a positive predictive rate of 95.8%. There were
      significant differences between Sonazoid-enhanced US and contrast-enhanced CT for
      sensitivity and accuracy (both p < 0.05). CONCLUSION: Sonazoid-enhanced US has a
      higher sensitivity and accuracy for the diagnosis of hepatic malignancies than
      contrast-enhanced CT.

PMID- 19092272
TI  - Imaging of hepatocellular carcinoma: qualitative and quantitative analysis of
      postvascular phase contrast-enhanced ultrasonography with sonazoid. Comparison
      with superparamagnetic iron oxide magnetic resonance images.
AB  - PURPOSE: To evaluate the usefulness of vascular phase images of contrast-enhanced
      ultrasonography (CE-US) with Sonazoid for hepatocellular carcinomas (HCCs), a
      retrospective, comparative study was conducted of images of HCCs obtained by CE
      US and superparamagnetic iron oxide (SPIO) magnetic resonance imaging (MRI) and
      evaluated qualitatively and quantitatively. METHODS: Seventy-seven patients with
      88 HCCs who received CE-US and SPIO-MRI were reviewed. The ratio of the
      echogenicity of the tumor and nontumor areas was calculated with postvascular
      phase CE-US (postvascular phase ratio). The ratio of the intensity of the
      nontumor to tumor areas on SPIO-enhanced MRI (SPIO intensity index) was also
      calculated. The Pearson correlations were calculated for all values between the
      postvascular phase ratio and SPIO intensity index for quantitative comparison.
      These images were also compared qualitatively for the detection rate of the
      tumors. RESULTS: The sensitivities of CE-US and SPIO-MRI in detecting tumors were
      98 and 95%, respectively (nonsignificant, chi(2) test). The postvascular phase
      ratio correlated with the SPIO intensity index for HCCs (Pearson r = 0.803, p <
      0.05). The image conformity of the result from the liver parenchymal phase CE-US
      and SPIO-MRI was 92%. Dedifferentiation spots of nodule-in-nodule HCCs were
      detected in 4 (80%) of 5 on postvascular phase images of CE-US, and in 2 (40%) of
      5 on SPIO-MRI (nonsignificant, chi(2) test). CONCLUSIONS: Postvascular phase
      images of CE-US with Sonazoid appear promising as an alternative to SPIO-enhanced
      MRI. Further study cases are needed to confirm the usefulness of postvascular
      phase images of CE-US compared to SPIO-MRI for the detection of dedifferentiation
      foci in hepatic tumors.

PMID- 19092273
TI  - Intranodular blood supply correlates well with biological malignancy grade
      determined by tumor growth rate in pathologically proven hepatocellular
      carcinoma.
AB  - This study was carried out to investigate whether intranodular blood supply in
      histologically proven well-differentiated hepatocellular carcinomas (HCCs)
      correlates with tumor growth rates. A total of 52 well-differentiated HCCs were
      enrolled in this study. Ultrasound angiography with intra-arterial CO(2)
      microbubble injection was performed in all 52 HCCs and computed tomography during
      arterial portography was performed in 21 of the 52 HCCs. Tumor volume doubling
      time (TVDT) was measured in all 52 nodules by B-mode ultrasonography performed at
      2- to 3-month intervals for a follow-up period of at least 6 months (range: 6
      months to 8 years) with respect to arterial vascularity. In the hypervascular (n
      = 27), isovascular (n = 9), and hypovascular nodules (n = 16), the mean values of
      TVDT (mean +/- SD) were 79 +/- 131, 98 +/- 227, and 782 +/- 324 days,
      respectively (r(s) = 0.722, p < 0.0001). Concerning portal blood supply, the mean
      TVDT in nodules in which the portal supply was reduced (n = 5) was 178 +/- 78
      days compared with 592 +/- 211 days in nodules in which the portal supply was
      preserved (n = 11), with a significant difference (p < 0.01). Five nodules in
      which the portal supply was preserved did not enlarge during the follow-up period
      of 3-5 years. There was a significant correlation among the three groups (r(s) =
      0.804, p < 0.05). In conclusion, intranodular blood flow dynamics in patients
      with well-differentiated HCC reflect the biological malignancy or cancer
      progression in the process of multistep hepatocarcinogenesis, suggesting the
      importance of this parameter in deciding on a treatment strategy. In other words,
      nodules in which arterial vascularity is present and those in which the portal
      blood flow is reduced should be treated for reasons such as a short doubling time
      and the risk of rapid progression to artery-dominant classical HCC.

PMID- 19092274
TI  - Magnetic resonance imaging of hepatocellular carcinoma.
AB  - In hepatocellular carcinomas (HCCs), T(1) shortening occurs due to internal
      protein, fat, copper, iron, hypercellularity, or a combination thereof. T(1)
      weighted magnetic resonance imaging (MRI) is obtained with a non-fat-suppressed
      phase shift [in- (4 ms) and opposed- (2 ms) phase] gradient-echo sequence.
      Internal fat deposition is often (36%) seen in well-differentiated HCCs between
      1.1 and 1.5 cm in size. T(2)-weighted MRI is crucial in differentiating HCCs from
      premalignant or borderline lesions in cirrhosis and serves as a tie breaker for
      small early-enhancing lesions. Gadolinium-enhanced MRI has advantages over
      contrast-enhanced CT: greater contrast enhancement, smaller volume of contrast,
      and less frequent adverse reactions. Double hepatic arterial-phase imaging has
      been performed in many centers, allowing less frequent off-timing arterial-phase
      imaging and improved temporary resolution. Hypervascular HCCs often show 'corona'
      enhancement in the late hepatic arterial phase, which makes it possible to
      distinguish small HCCs from enhancing pseudolesions. Liposoluble gadolinium
      chelate (e.g., Gd-EOB-DTPA) behaving both as an extracellular and hepatobiliary
      agent is very useful in the diagnosis. Diffusion-weighted imaging has become a
      routine imaging tool thanks to the parallel imaging technique. However, diffusion
      weighted imaging may not significantly improve detection, characterization, or
      estimation of tumor grade for HCCs, and it should still be supplementary. In
      summary, we believe MRI outperforms CT in the diagnosis of HCCs.

PMID- 19092275
TI  - Magnetic resonance imaging of hepatocellular carcinoma using contrast media.
AB  - Magnetic resonance imaging (MRI) has been widely used for evaluation of focal
      lesions associated with hepatic carcinogenesis including hepatocellular carcinoma
      (HCC). By providing better tissue contrast compared to ultrasonography and
      computed tomography, MRI is considered the most sensitive modality for diagnosis
      of HCC. Dynamic MRI using gadolinium-based extracellular fluid (ECF) agents is
      useful for detection of hypervascular tumors and lesion characterization but has
      limitations in the diagnosis of hypovascular HCCs and lesion characterization of
      nonhypervascular tumors. MRI using superparamagnetic iron oxide agents may be
      useful for detecting and characterizing lesions that were not seen on dynamic MRI
      using ECF agents, but finding well-differentiated HCC and differentiating it from
      a dysplastic nodule can be difficult in some cases. Hepatobiliary agents that can
      be used in both dynamic MRI and delayed hepatobiliary phase imaging have great
      potential for improving characterization of focal lesions associated with hepatic
      carcinogenesis. Further studies are necessary to determine their roles in
      evaluation and management of HCCs.

PMID- 19092276
TI  - Validation of a new prognostic staging system for hepatocellular carcinoma: a
      comparison of the biomarker-combined Japan Integrated Staging Score, the
      conventional Japan Integrated Staging Score and the BALAD Score.
AB  - OBJECTIVES: The conventional Japan Integrated Staging (c-JIS) score has been
      reported to effectively stratify patients with hepatocellular carcinoma (HCC).
      Recently, two new staging systems, the biomarker-combined JIS (bm-JIS) score and
      the BALAD score, have been proposed. Both staging systems include three tumor
      markers: alpha-fetoprotein (AFP), lens culinaris agglutinin-reactive AFP and des
      gamma-carboxy prothrombin specific for HCC. The aim of this study is to evaluate
      the performance of these three staging systems. METHODS: A total of 1,173 HCC
      patients were included in this study. The stratification ability and prognostic
      predictive power were compared between these three staging systems. RESULTS:
      These three staging systems effectively predicted the patient survival. When
      accounting for the best prognostic subgroup of each staging systems (i.e. score
      of 0), there were significant differences between the bm-JIS score and the BALAD
      score and, likewise, between the c-JIS score and the BALAD score. The likelihood
      ratio chi(2) test showed the highest value and the Akaike information criterion
      value was lowest in the bm-JIS score. CONCLUSIONS: The bm-JIS score showed good
      stratification ability and was thus demonstrated to be a better predictor of the
      prognosis than the c-JIS score and the BALAD score, especially for the patients
      with a good prognosis.

PMID- 19092277
TI  - PIVKA-II is the best prognostic predictor in patients with hepatocellular
      carcinoma after radiofrequency ablation therapy.
AB  - OBJECTIVE: This study was undertaken to assess the prognostic predictor in
      patients with hepatocellular carcinoma (HCC) after radiofrequency ablation (RFA).
      METHODS: This study retrospectively evaluated clinical outcomes in a cohort of
      179 Child-Pugh stage A cirrhotic patients who received curative RFA for naive HCC
      within Milan criteria. The median follow-up period was 40.5 months. RESULTS: The
      cumulative survival rate was significantly lower in patients with prothrombin
      induced by vitamin K absence or antagonist II (PIVKA-II) > or =100 mAU/ml
      compared with PIVKA-II <100 mAU/ml (58.0 vs. 84.0% at 5 years; p < 0.001). The
      cumulative recurrence-free survival rates were significantly lower in patients
      with PIVKA-II > or =100 mAU/ml compared with PIVKA-II <100 mAU/ml (12.1 vs. 16.9%
      at 5 years; p < 0.032). The cumulative rate of maintaining period within Milan
      criteria was significantly lower in patients with PIVKA-II > or =100 mAU/ml
      compared with PIVKA-II <100 mAU/ml (34.1 vs. 55.6% at 5 years; p < 0.001). Cox
      regression analysis showed that low serum albumin (<3.5 g/dl; p = 0.002, RR 3.75,
      CI 1.64-8.56), a high level of PIVKA-II (> or =100 mAU/ml; p = 0.04, RR 3.15, CI
      1.45-6.87), and multiple nodules (p = 0.021, RR 2.61, CI 1.15-5.91) were
      independently significant mortality risk factors. CONCLUSION: In patients with
      Child-Pugh stage A HCC, the PIVKA-II level is the best prognostic predictor after
      curative RFA.

PMID- 19092278
TI  - Response evaluation of transcatheter arterial chemoembolization in hepatocellular
      carcinomas: the usefulness of sonazoid-enhanced harmonic sonography.
AB  - BACKGROUND: The purpose of this study was to investigate if Sonazoid-enhanced
      harmonic ultrasonography (US) could be used to evaluate the responses of
      hepatocellular carcinomas (HCCs) to treatment with transcatheter arterial
      chemoembolization (TACE). PATIENTS AND METHODS: Forty-three HCCs that had been
      treated by TACE were evaluated by Sonazoid-enhanced harmonic US and dynamic
      computed tomography (CT) approximately 1 week after their treatment. The
      detection rates of residual tumor blood supply using the two modalities were
      compared. Two months after chemoembolization, 16 of the 43 HCCs, which had no
      additional local treatment, were followed up with dynamic CT. The results of
      contrast-enhanced harmonic US and dynamic CT 1 week after chemoembolization were
      analyzed and compared with follow-up dynamic CT results. RESULTS: The detection
      rates of positive enhancement with Sonazoid-enhanced harmonic US and dynamic CT 1
      week after TACE were 25 (58.1%) of 43 lesions and 17 (39.5%) of 43 lesions,
      respectively. Sonazoid-enhanced harmonic US was significantly more sensitive than
      dynamic CT in depicting the residual tumor blood supply to HCCs 1 week after TACE
      (p < 0.01; chi(2) test). The Sonazoid-enhanced harmonic US results of the 16
      lesions 1 week after chemoembolization were consistent with the follow-up results
      of dynamic CT 2 months after chemoembolization. CONCLUSIONS: Sonazoid-enhanced
      harmonic US appears to be a highly sensitive and accurate modality for evaluating
      responses of HCCs shortly after TACE.

PMID- 19092279
TI  - Combination therapy with S-1 and pegylated interferon alpha for advanced
      hepatocellular carcinoma.
AB  - PURPOSE: There are currently no effective treatments for patients with advanced
      hepatocellular carcinoma (HCC) with vascular invasion or extrahepatic metastases.
      We evaluated the efficacy and safety of combination therapy with S-1 and
      pegylated interferon (PEG-IFN)-alpha for advanced HCC. METHODS: A total of 22
      patients received combination therapy with S-1 and PEG-IFN. One cycle of the
      combination therapy consists of oral S-1 (80 mg/m(2)) administration and
      subcutaneous PEG-IFN injection (PEG-IFN-alpha-2a 90 microg weekly or PEG-IFN
      alpha-2b 50 microg weekly) for 4 weeks with 1- to 2-week intervals. RESULTS: One
      patient was evaluated as complete response, 6 as partial response, 8 as stable
      disease, and 6 as progressive disease. One patient was not evaluable because
      therapy had to be discontinued as a result of jaundice. The median survival time
      was 15.3 months (95% CI: 4.4-26.2 months). The 1- and 2-year survival rates were
      54.9 and 36.6%, respectively. The overall response rate was 31.8% and the disease
      control rate was 68.2%. Grade 3 neutropenia (18.2%), leukopenia (9.1%), anemia
      (9.1%), and thrombocytopenia (18.2%) were observed. Grade 4 toxicities were not
      observed. CONCLUSION: Combination therapy with S-1 and PEG-IFN is effective and
      feasible, and is therefore a promising regimen for advanced HCC.

PMID- 19092280
TI  - Systemic chemotherapy of hepatocellular carcinoma--Korean experience.
AB  - Surgical resection, transarterial chemoembolization, percutaneous ethanol
      injection therapy, radiofrequency ablation, and orthotopic liver transplantation
      are generally accepted treatment modalities in hepatocellular carcinoma, but
      there has been no standard therapy for patients at the advanced stage. Several
      combinations of various cytotoxic agents have been tried in Korea, but definite
      conclusions could not be drawn because of small sample size, heterogenous
      populations among studies, several biases, and lack of a control arm. There has
      been no evidence so far that either of the combination chemotherapies is superior
      to single-agent chemotherapy or systemic chemotherapy has any clinical benefit in
      terms of patient survival. Recent advances in molecular biology have identified
      several important signal transduction pathways during hepatocarcinogenesis, which
      enables us to control the key elements of these signaling pathways. Accordingly,
      several new 'targeted agents' have been developed and are under clinical trial at
      present. In contrast to previous cytotoxic agents, most targeted agents do not
      induce regression of tumors but stabilize disease progression. Sorafenib is the
      first drug proven to prolong survival in advanced stage patients. However, the
      survival benefit is still not satisfactory; therefore, future trials should be
      conducted regarding the combination of sorafenib with other preexisting treatment
      modalities or new targeted agents.

PMID- 19092281
TI  - Surgical treatment of hepatocellular carcinoma: comparison of resection and
      transplantation.
AB  - The treatment of hepatocellular carcinoma (HCC) has progressed remarkably over
      the last years. In patients with good hepatic functional reserve, liver resection
      should be considered as the therapeutic modality for local control of primary
      HCC, including a large tumor, or multiple HCCs with vascular invasion. Anatomic
      resection involves systematic elimination of the main tumor and its minute
      metastases. In cases with poor hepatic functional reserve, however, liver
      transplantation may be a better therapeutic option depending on patient age and
      tumor-related factors. Patients with tumors satisfying the Milan criteria (or its
      extended criteria) are good candidates for liver transplantation. We analyzed the
      findings from 100 patients with HCC who underwent living donor liver
      transplantation. The overall survival at 3 and 5 years after liver
      transplantation was 79 and 78%, respectively, with a median follow-up of 45
      months. The treatment algorithm, based on evidence accrued from published papers,
      is now available and is useful for determining the therapeutic choice based on
      the tumor- and liver function-related conditions.

PMID- 19092282
TI  - Current role of surgery in treatment of early stage hepatocellular carcinoma:
      resection versus liver transplantation.
AB  - Hepatocellular carcinoma (HCC) is the most common malignancy of the liver and is
      most commonly associated with hepatitis B infection in Korea. Although liver
      resection is regarded as a potentially curative treatment option, it is only
      feasible in less than 20% of patients. The reason for this is that HCC arises in
      cirrhotic livers and is often multicentric. Liver transplantation (LT) which
      could be used in the treatment both of the tumor and background liver seems to be
      a rational approach for early stage patients with decompensated liver cirrhosis.
      Current good selection criteria of LT for HCC are the Milan criteria: 1 HCC
      nodule < or =5 cm in diameter or 3 nodules < or =3 cm. By restricting LT to
      patients within the Milan criteria, the 4-year disease-free survival rate was
      more than 80%, which is comparable to that of a transplant candidate without HCC.
      However, there are serious limitations for the wider application of LT for HCC:
      (1) organ shortage, (2) risk to a live donor, (3) high cost, and (4) lifelong
      immunosuppression. For this reason, for a patient with early stage HCC and with
      Child A cirrhosis in whom partial hepatectomy is possible, the choice of primary
      treatment with curative intent is still under debate.

PMID- 19092283
TI  - Corrected and uncorrected near and distance vision with ReSTOR compared to
      monofocal intraocular lens implantation after cataract surgery: a pooled
      analysis.
AB  - BACKGROUND/AIM: To evaluate distance and near vision-related benefit after
      implantation of ReSTOR multifocal intraocular lenses (IOLs) following cataract
      surgery. METHODS: Two prospective open-labeled nonrandomized studies were pooled.
      Patients' perception of benefit was assessed with the TyPE, administered at
      baseline and after each eye surgery. RESULTS: A total of 499 patients received
      ReSTOR IOLs, and 173 received monofocal IOLs. The distance vision of monofocal
      and ReSTOR patients improved equally with and without glasses. A greater
      improvement in near vision without glasses was reported by ReSTOR-implanted
      patients as early as after the 1st eye surgery (p < 0.0001). More ReSTOR patients
      than monofocal patients reported independence from glasses after the 1st eye
      surgery (64 vs. 52%; p = 0.0002). This difference had increased after the 2nd eye
      surgery (85 vs. 51%; p < 0.0001). CONCLUSIONS: The improvement in near vision
      without glasses was significantly more evident in ReSTOR patients, allowing the
      majority of them to be free of glasses.

PMID- 19092284
TI  - Effect of basic fibroblast growth factor in transgenic mice: corneal epithelial
      healing process after excimer laser photoablation.
AB  - PURPOSE: To evaluate the role of preparedbasic fibroblast growth factor (bFGF)
      eyedrops in corneal epithelial healing of transgenic mice after excimer laser
      photoablation. MATERIALS AND METHODS: In our prospective case series, 60 eyes of
      30 mice had uneventful bilateral excimer laser photoablation. In each mouse, 1
      eye received the standard topical postoperative therapy with tobramicin,
      diclofenac and dexamethasone eyedrops, plusbFGF eyedrops 5 microg/10 microl PBS 3
      times a day for 1 week, or until corneal reepithelialization was complete. The
      fellow eye served as the control and received the standard postoperative therapy
      plus placebo. The mice were monitored daily, commencing the day after surgery and
      for 7 days, in order to evaluate the corneal reepithelialization rate by using a
      video slitlamp camera with a cobalt blue light. The mean diameter of the corneal
      wounds was measured. Videotaped images were recorded and analyzed by computer
      planimetry. RESULTS: All the eyes treated withbFGF eyedrops healed completely
      before day 5 after surgery, with a mean reepithelialization time of 90 +/- 12 h
      (standard deviation); the mean reepithelialization time was 124 +/- 10 h in those
      eyes receiving placebo. There were no statistically significant differences
      between the 2 groups in corneal haze presentation during the follow-up, perhaps
      because the time period was too brief (7 days). However, corneal clarity on
      slitlamp biomicroscopy was greater in the study group than in the control group.
      No side effects or toxic effects were documented. CONCLUSIONS: These data suggest
      that the bFGF significantly accelerates epithelial healing after excimer
      photoablation. A further clinical study should be performed to prove the results
      obtained in this study as well as the long-term efficacy of bFGF to prevent
      corneal haze.

PMID- 19092285
TI  - Differential involvement of Ca2+ and actin filament in leukocyte shape change.
AB  - At the sites of inflammation, leukocytes are confronted with mediators which
      induce different cellular responses like chemotaxis, degranulation and
      respiratory burst. Morphologically, these responses are accompanied by changes in
      the cells' shape. In this study, we investigated the involvement of the actin
      cytoskeleton and Ca2+ in the shape change responses of human eosinophils and
      neutrophils to chemoattractants and correlated the obtained findings to
      degranulation and respiratory burst using flow cytometry. Shape change was
      recorded as an increase in forward scatter. Degranulation was measured as the
      cell surface upregulation of the granule-associated marker CD63. Respiratory
      burst was determined fluorimetrically as the oxidation of dihydrorhodamine 123.
      The involvement of actin filaments and phospholipase C (PLC) was investigated
      with the actin inhibitor cytochalasin B and the selective PLC inhibitor U-73122,
      respectively. The data that we obtained demonstrated that granulocytes exhibit 2
      distinct types of shape change responses when stimulated with chemoattractants:
      (i) one type is induced by chemokines like eotaxin and interleukin 8, which are
      poor degranulators, and also by classical chemoattractants, C5a and formyl
      methionyl-leucyl-phenylalanine; this shape change depends on the activation of
      PLC and functional actin filaments, but does not require Ca2+ influx from
      outside; (ii) the second type of shape change is not stimulated by chemokines,
      but can be seen with classical chemoattractants which are also potent inducers of
      degranulation and respiratory burst. This type of shape change does not require
      any functional actin filaments, but appears to be a consequence of degranulation
      and depends essentially on the activation of PLC and Ca2+ influx from the
      extracellular space.

PMID- 19092286
TI  - Role of calcium malabsorption in the development of secondary hyperparathyroidism
      after biliopancreatic diversion.
AB  - Secondary hyperparathyroidism (SH) is a frequent metabolic complication of
      bariatric surgery. Around 70%of patients who undergo biliopancreatic diversion
      (BPD) have this complication in the long term. The aim of this study was to
      evaluate the relative influence of vitamin D deficiency and calcium malabsorption
      in the development of SH in patients who underwent BPD. We reviewed the mean
      values of PTH throughout the post-operative follow-up and of related biochemical
      data (25-hydroxyvitamin D, calcium, magnesium) of 121 patients who underwent BPD
      at our institute from November 1996 to November 2004 (mean follow-up 66 months).
      Mean PTH correlated negatively with mean 25-hydroxyvitamin D (r=-0.27, p=0.003)
      and with urinary calcium(r=-0.19, p=0.047), and positively with age (r=0.22,
      p=0.018). However, a high mean PTH was found in 48.7% patients with mean 25
      hydroxyvitamin D >or=30 ng/ml and in 80.0% patients with mean 25-hydroxyvitamin D
      between 20 and 30 ng/ml. The mean PTH was normal in 5 patients without calcium
      supplements at present, and progressively increased in parallel to the calcium
      dose in the rest of patients, although mean 25-hydroxyvitamin D levels were not
      related to the calcium dose. Our data suggest that individual differences in
      active and/or passive calcium absorption determine intractable SH after BPD in
      around half of the patients who have normal levels of 25-hydroxyvitamin D and in
      80% of patients with 25-hydroxyvitamin D levels between 20 and 30 ng/ml after
      BPD, worsening with age.

PMID- 19092287
TI  - Iodine status and thyroid volume changes during pregnancy: results of a survey in
      Aran Valley (Catalan Pyrenees).
AB  - The Aran Valley (Catalan Pyrenees, Spain) has a long-standing history of iodine
      deficiency. A survey was performed to determine the prevalence of iodine
      deficiency (urinary iodine<150 microg/l) in pregnant women from this region
      during the 1st and 3rd trimesters of gestation and to evaluate the changes in
      thyroid volume (TV). Of all the registered pregnancies in the area, in the first
      semester of the year 2000, 35 women (90%) were studied. Urinary iodine (UI) was
      measured and a thyroid ultrasonography performed during the 1st and 3rd trimester
      and their iodized salt consumption was recorded. Of the whole group, 77.1% of
      pregnant women reported regular intake of iodized salt.Median UI in the first
      trimester was 134.5 microg/l. Iodine deficiency was observed in 57.1%of women in
      the 1st trimester and in 46.7% in the 3rd trimester (p=0.1). In 10 women
      supplemented with iodine (150 microg/day) from the 1st trimester, median UI
      increased from 138.5 microg/l in the 1st trimester to 168 mug/l in the 3rd
      trimester (p=0.037), and no changes were observed in the rest. TV increased in
      the whole group during pregnancy (median 7.5 ml in the 1st trimester vs 9.5 ml in
      the 3rd trimester; p<0.001). The change in TV was significant in those cases with
      iodine deficiency in the 1st trimester, 3rd trimester or both (median 7.5ml in
      the 1st trimester vs 10.01 ml in the 3rd trimester; p=0.001) and between
      multiparous women (8.2 vs 10.9 ml; p=0.005). In 2000, iodine deficiency among
      pregnant women in the Aran Valley was still very high. Iodine deficiency as well
      as multiparity contributes to goitrogenesis during pregnancy. Taking this data in
      account, pre-conceptional supplements with iodine are required for its
      prevention.

PMID- 19092288
TI  - Prevalence and causes of undiagnosed hyperthyroidismin an adult healthy
      population. The Tromso study.
AB  - BACKGROUND: The causes of subclinical hyperthyroidism have only been reported
      from clinical studies. AIM: To determine the prevalence and pathological causes
      of reduced serum TSH levels in subjects recruited from an epidemiological survey.
      MATERIAL/SUBJECTS AND METHODS: Serum TSH was measured in 7954 subjects in the 5th
      Tromso study. Subjects with serum TSH<0.50 mIU/l, not using T4, without a
      previous diagnosis of thyroid disease, without serious concomitant disease, and
      younger than 80 yr, were invited for a re-examination. If low serum TSH was
      persistent, thyroid scintigraphy was performed. RESULTS: Among the 4962 subjects
      that met the inclusion criteria, serum TSH was <0.50 mIU/l in 105 subjects.
      Twelve subjects had a suppressed serum TSH level (<0.05 mIU/l). Two of these were
      lost to follow-up, 4 had Graves' disease, 4 had adenoma, and 2 had multinodular
      goiter. In the 93 subjects with serum TSH 0.05-0.5 mIU/l, 55 were re-examined, of
      whom 35 had normalized their serum TSH level. In the remaining 20 subjects, 1 had
      Graves' disease, 6 had adenoma (of which 2 were toxic adenomas), 7 had
      multinodular goiter, and 6 were considered normal. Among the 521 subjects using
      T4, 70 (13.4%) had a suppressed serum TSH level. CONCLUSIONS: Most of the
      subjects with a suppressed serum TSH level will be on T4 medication. Otherwise,
      if the suppressed serum TSH level is found by chance, this probably represents a
      clinically important thyroid pathology. Also, in subjects with a persistently low
      serum TSH level (0.05-0.5 mIU/l) most will have a pathological thyroid scan.

PMID- 19092289
TI  - Prevalence of interrelated autoantibodies in thyroid diseases and autoimmune
      disorders.
AB  - OBJECTIVE: We determined the autoantibody profile in autoimmune thyroid diseases
      (AITD) and examined the distribution of thyroid-related autoantibodies in other
      autoimmune disorders. METHODS: We tested sera from 234 patients with Graves'
      disease (GD), 130 with Hashimoto's thyroiditis (HT), 249 with other autoimmune
      diseases, and 50 healthy controls by enzyme-linked immunosorbent assay or
      radioimmunoassay. RESULTS: Autoantibodies except TSH receptor antibody (Ab), anti
      thyroglobulin (Tg) Ab and anti-thyroid peroxidase (TPO) Ab were not significantly
      prevalent in patients with AITD despite a significantly high elevation of thyroid
      related Ab. Significant prevalence of autoantibodies related to AITD was observed
      in type 1 diabetes patients. Elevation of anti-Tg Ab was seen in patients with
      primary biliary cirrhosis (PBC) and autoimmune hepatitis (AIH), and anti-TPO Ab
      was elevated in patients with PBC. Although the prevalence of anti-acetylcholine
      receptor Ab and systemic lupus erythematosus (SLE)- related Ab was significant in
      AIH, primary Sjogren's syndrome (pSS)-related Ab were also found in both liver
      diseases. In myasthenia gravis (MG) patients, thyroid-related Ab and pSS-related
      Ab were detected in both MG groups, although SLE-related Ab were limited to the
      anti-muscle specific kinase Ab-positive MG patients. In patients with connective
      tissue diseases, anti- Tg Ab and anti-TPO Ab were significantly prevalent.
      CONCLUSION: Thyroid-related Ab were significantly elevated in all autoimmune
      diseases. Conversely, the elevations of Ab were not significant in the patients
      with AITD, suggesting a close relationship between AITD and other immune-mediated
      diseases.

PMID- 19092290
TI  - Long-term follow-up of patients with hyperthyroidism due to Graves' disease
      treated with methimazole. Comparison of usual treatment schedule with drug
      discontinuation vs continuous treatment with low methimazole doses: a
      retrospective study.
AB  - Antithyroid drugs may be proposed as the firstline therapy for hyperthyroidism
      due to Graves' disease since some patients undergo prolonged remission after drug
      withdrawal. On the other hand, some studies, though controversial, indicated that
      methimazole (MMI) has some immunomodulating activity. We retrospectively analyzed
      384 consecutive patients newly diagnosed with Graves' disease in the years 1990
      2002 to ascertain whether long-term therapy with low doses of MMI may prevent
      relapse of thyrotoxicosis. Two hundred and forty-nine patients were included in
      our study. The date of reduction of MMI dose to 5 mg/day was considered time 0
      for survival analysis. In 121 MMI was discontinued in less than 15 months after
      time 0 (group D), while in the remaining 128 a daily MMI 2.5-5 mg dose was
      maintained (group M). One hundred and thirty-five patients were excluded for
      inadequate response to MMI, relapse of thyrotoxicosis that could be related to an
      improper withdrawal or reduction of MMI, inadequate or too short followup, iodide
      contamination, steroid or interferon therapy, pregnancy or post-partum. D and M
      groups did not differ for clinical and hormonal parameters except age, which was
      lower in D (p=0.019). Age > vs < 35 yr was relevant in survival analysis;
      therefore patients were divided in 2 groups according to this age cut-off. In
      younger patients relapse of thyrotoxicosis occurred in 15 patients of group D 2.4
      39.6 months (median 19.0) after time 0, and 8 M after 5.9-40.0 (21.3) months,
      while 14 D and 5 M maintained euthyroidism until the end of the observation after
      31.8-95.3 (56.6) months and 30.4-62.1 (46.5) months, respectively. Survival
      analysis indicated that the risk of relapse was similar in group D and M. In
      older patients relapse of thyrotoxicosis occurred in 40 patients of group D after
      8.2-65.8 (25.4) months and 29 M after 5.8-62.5 (22.4) months, while 52 D and 86 M
      maintained euthyroidism until the end of the observation, 20.1-168.0 (46.7)
      months and 24.1-117.4 (53.4) months respectively. Survival analysis indicated
      that the risk of relapse was increased in group D. Therefore long-term treatment
      with low doses of MMI seems to prevent relapse in Graves' disease in patients
      above 35 yr of age. This should be confirmed in a prospective study.

PMID- 19092291
TI  - Unexpected histological findings of lesions diagnosed in the adrenal region in a
      series of 420 patients submitted to adrenal surgery. Review of our experience.
AB  - INTRODUCTION: The incidence of adrenal incidentalomas is reported to be up to 30%
      in the current literature; nevertheless, in some patients undergoing surgery, a
      final diagnosis of non-adrenal origin of the mass is performed. In this paper we
      present our experience of 13 patients with unexpected histological findings of
      lesions diagnosed in the adrenal region. PATIENTS AND METHODS: From June 1986 to
      December 2004, 420 patients underwent adrenalectomy in our Department. Since the
      introduction of videolaparoscopic technique in 1993, 228 adrenalectomies have
      been performed videolaparoscopically. Pre-operative diagnosis was: incidentaloma
      (34.0% of patients), Conn's adenoma (29.0%), Cushing's adenoma (13.9%),
      pheochromocytoma (8.8%), suspicious metastasis (7.3%), Cushing's disease (6.0%),
      other (1.0%). RESULTS: Final histology revealed an unexpected diagnosis of non
      adrenal origin of the mass in 13 patients (3.1%). Histology demonstrated a benign
      neurogenic tumor in 10 patients. In the other 3 patients diagnosis was
      respectively of lymphnode, hemangioma and a gastric metastasis of melanoma. Five
      patients out of 7 had a successful laparoscopic resection of the lesion. Mean
      operative time in this group was higher compared to laparoscopic resection for
      adrenal lesion (95.3 min vs 73.2 min). CONCLUSION: A small percentage of our
      patients (3.1%) demonstrated unexpected findings of the lesion pre-operatively
      misinterpreted as an adrenal mass. Despite a complete pre-operative assessment,
      adrenal lesions might reveal a different origin, increasing the surgical
      challenge as well as the morbidity for the patient.

PMID- 19092292
TI  - Effects of estrogen and estrogen-progesteron on serum nitric oxide metabolite
      concentrations in post-menopausal women.
AB  - Estrogens have some anti-atherosclerotic properties and they influence nitric
      oxide (NO) production. The aim of this study was to determine NOx levels in post
      menopausal women and the effect of estrogen/estrogen-progesteron therapy (ET/EPT)
      on plasma NO levels. Eighty postmenopausal women (M1) comprising 26 with
      surgically induced menopause (ET1), mean age 50.9+/-2.9 yr, and 54 with
      physiological menopause (EPT1), mean age 50.5+/-3.0 yr, were studied. Forty
      healthy pre-menopausal women, mean age 48.3+/-2.3 yr were the controls (C). The
      post-menopausal women were treated for 4 months: group ET1 with ET and group EPT1
      with EPT. Serum estradiol (E2), FSH, NOx and lipid profile before and after
      therapy were measured. NOx levels were lower in group M1 than in group C (8.75+/
      1.57 vs 10.27+/-2.62, p<0.01) and increased after hormonal therapy (10.65+/
      2.38). NOx concentration showed significant positive correlation with E2 (r=0.25,
      p<0.05). Total cholesterol (240.9+/-43.2), LDL-cholesterol (155.2+/-33.6),
      triglycerides (124.8+/-54.1), and apolipoprotein B (1.52+/-0.33) were higher in
      group M1 than in group C (223.1+/-44.3, 133.0+/-38.2, 108.3+/-52.9, and 1.12+/
      0.36, respectively), and after ET/EPT they decreased to the values observed in
      group C. There were no correlations between NO and lipids or apolipoproteins.
      CONCLUSIONS: ET and EPT improve NOx synthesis and endothelial relaxation.
      Medroxyprogesterone acetate added to E2 does not significantly influence NOx
      levels.

PMID- 19092293
TI  - Color-coded duplex endoscopic ultrasound of the adrenals.
AB  - Imaging of the adrenals by endoscopic ultrasound (EUS) is a valuable technique
      for detection and localization of adrenal lesions, but endosonomorphological
      tumor distinction remains difficult. In this single-center study, the amount of
      blood flow in common adrenal lesions, such as adrenal adenomas, adrenal
      hyperplasia, and pheochromocytomas, was visualized by color-coded duplex EUS (CD
      EUS) and was retrospectively analysed. Therefore, we reviewed our EUS database to
      evaluate and correlate the perfusion patterns of common adrenal lesions with
      histologically confirmed diagnosis, possible malignancy, and
      endosonomorphological features such as echogeneity, echostructure, and tumor
      size. CD-EUS was performed using an endosonoscope Pentax FG 32 UA with a
      longitudinal 7.5 MHz sector array and Hitachi EUB 525 ultrasound system. In 38
      consecutive patients (male=19; female=19; age: mean 53+/-16 yr SD), perfusion
      patterns of 46 histologically confirmed adrenal, para- or extra-adrenal lesions
      of adrenal origin (adenoma: no.=20; nodular hyperplasia: no.=11;
      pheochromocytoma: no.=15; diameter 26+/-15 mm, range 6-70 mm) were analyzed and
      classified semiquantitatively as "not" (no.=24), "slightly" (no.=12),
      "moderately" (no.=4) or "highly" (no.=6) hypervascularized. Compared to adenomas
      (p=0.003) and nodular hyperplasia (p=0.047), pheochromocytomas showed a
      significantly higher grade of perfusion. There was no relationship between
      perfusion patterns and localization of pheochromocytomas (adrenal: 8;
      paraadrenal: 3; extra-adrenal: 4). Vascularization was not statistically
      associated with tumor echogeneity, echostructure, malignancy or tumor size. CD
      EUS is an additional tool for adrenal endosonographic tumor distinction and seems
      to improve the endosonographic detection of pheochromocytomas by visualization of
      hypervascularization. As an overlap of perfusion patterns exists, CD-EUS findings
      must be interpreted in the context of clinical, laboratory and chemical results.

PMID- 19092294
TI  - Absence of thyrotropin-induced increase in leptin levels in patients with history
      of differentiated thyroid carcinoma undergoing recombinant human thyrotropin
      testing.
AB  - BACKGROUND: Some extra-thyroid effects of TSH have been described in vitro and in
      vivo. TSH has recently been suggested to induce interleukin-6 secretion by
      adipocytes. Leptin is the main protein secreted by adipose tissue. OBJECTIVE: The
      aim of our study was to evaluate the acute effect of the recombinant human TSH
      (rhTSH)-induced TSH surge on serum leptin levels in thyroidectomized patients
      undergoing levothyroxine (L-T4) suppressive therapy for differentiated thyroid
      carcinoma (DTC). DESIGN: A cohort of 15 female DTC patients was evaluated.
      Standard rhTSH testing was performed. Leptin, TSH, thyroid hormones, and
      thyroglobulin were measured before and 3, 6, and 9 days after rhTSH testing. Some
      metabolic parameters were also evaluated at the baseline. RESULTS: Baseline
      leptin levels were 12.2+/-3.2 microg/l. Only body mass index (BMI) correlated
      significantly (p<0.05) with leptin levels. After rhTSH administration, TSH levels
      increased significantly (p<0.001), while thyroid hormones remained unchanged.
      Twenty hours after the last rhTSH administration, leptin (11.8+/-3.0 microg/l)
      levels were unchanged. The maximal TSH level was negatively related with BMI
      (p<0.05), but no correlation between maximal TSH and leptin levels after rhTSH
      was noted. CONCLUSIONS: Our in vivo experimental model suggests that an acute TSH
      increase after rhTSH testing is ineffective in changing circulating leptin
      levels.

PMID- 19092295
TI  - RAD52 polymorphisms contribute to the development of papillary thyroid cancer
      susceptibility in Middle Eastern population.
AB  - Genetic polymorphisms of DNA repair genes seem to determine the DNA repair
      capacity. We hypothesized that polymorphisms of genes responsible for DNA repair
      may be associated with risk of thyroid cancer. To evaluate the role of genetic
      polymorphisms of DNA repair genes in thyroid cancer, we conducted a hospital
      based case-control study in Saudi population. Two hundred and twenty-three
      incident papillary thyroid cancer cases and 229 controls recruited from Saudi
      Arabian population were analyzed for 21 loci in 8 selected DNA repair genes by
      PCR-restriction fragment length polymorphism including non-homologous end joining
      pathway genes LIGIV (LIGlV ASP62HIS, PRO231SER, TRP46TER), XRCC4 Splice
      33243301G>A and XRCC7 ILE3434THR; homologous recombination pathway genes XRCC3
      ARG94HIS and THR241MET, RAD51 UTR 15452658T>C, 15455419A>G, RAD52 2259 and
      GLN221GLU, conserved DNA damage response gene Tp53 PRO47SER, PRO72ARG, Tp53 UTR
      7178189A>C and base excision repair gene XRCC1 ARG194TRP, ARG280HIS, ARG399GLN,
      ARG559GLN. RAD52 GLN221GLU genotypes CG and variants carrying G allele showed
      statistical significance and very high risk of developing thyroid cancer compared
      to wild type [CG vs CC; p<0.001, odds ratio (OR)=15.57, 95% confidence interval
      (CI)=6.56-36.98, CG+GG vs CC; p<0.001, OR=17.58, 95% CI=7.44-41.58]. Similarly,
      RAD52 2259 genotypes CT and variant allele T showed a significant difference in
      terms of risk estimation (CT vs CC; p<0.05, OR=1.53, 95% CI=1.03-2.28, CT+TT vs
      CC; p<0.001, OR=1.922, 95% CI=1.31-2.82). Remaining loci demonstrated no
      significance with risk. Of the 21 loci screened, RAD52 2259 and RAD52 GLN221GLU
      may be of importance to disease process and may be associated with papillary
      thyroid cancer risk in Saudi Arabian population.

PMID- 19092296
TI  - Hyperparathyroidism 2 gene (HRPT2, CDC73) and parafibromin studies in two
      patients with primary hyperparathyroidism and uncertain pathological assessment.
AB  - HRPT2 and parafibromin studies improved the diagnostic accuracy in two patients
      with primary hyperparathyroidism (PHPT) referred to us after surgery, in whom the
      clinical data were at variance with the pathological diagnosis of adenoma and
      carcinoma, respectively. Patients were referred to us after parathyroidectomy.
      Patient #1 had had a 1.5-cm tumor easily removed with a histological diagnosis of
      parathyroid carcinoma and normocalcemia for 2 years. Re-examination of the
      histology showed no cardinal signs of parathyroid cancer. Patient #2, with severe
      PHPT, had had the removal of a 3.5-cm tumor described histologically as adenoma.
      Ten years later PHPT recurred and persisted despite removal of two mildly
      enlarged parathyroid glands that were histologically normal. Re-review of the
      initial histology showed a trabecular pattern, fibrous bands, and atypical
      mitoses, suggesting an atypical adenoma. Because of the suspicion that case #1
      could be an atypical adenoma and case #2 a carcinoma further molecular studies
      were performed. No HRPT2 and parafibromin abnormalities were identified in
      patient #1, strongly indicating a benign lesion. In patient #2, an HRPT2 germline
      mutation was found (E115X in exon 4) and associated with no parafibromin
      staining. These data, together with the clinical features, supported the
      suspicion of a parathyroid carcinoma that was confirmed by histological
      examination of further slides of the tumor, showing capsular and vascular
      invasion. A lung 1.5-cm nodule detected by computed tomography was excised.
      Histology showed a metastasis of parathyroid carcinoma. HRPT2 gene studies
      improved the diagnostic accuracy in 2 parathyroid tumors that are of uncertain
      type.

PMID- 19092297
TI  - The genetic ascertainment of multiple endocrine neoplasia type 1 syndrome by
      ancient DNA analysis.
AB  - Multiple endocrine neoplasia type 1 (MEN1) is a rare autosomal dominant inherited
      endocrine cancer syndrome characterised by parathyroid, pancreas, and anterior
      pituitary tumors. The disease responsible gene, MEN1, was identified in 1997 and
      localizes to chromosome 11q13 in a minimal 600 kb interval between PYGM and
      D11S449 loci. About 10-20% of MEN1 patients do not have any mutation in the
      coding region and/or in the exon-intron junctions of the MEN1 gene. In this case,
      familial haplotype analysis of the 11q13 region, in at least two generations of
      affected members, is the only possible genetic ascertainment of the disease. We
      performed a microsatellite haplotype analysis at 11q13 region in 8 living and 1
      deceased member of a MEN1 Italian family without any detected germline mutation
      of the MEN1 gene. The application of forensic techniques for ancient DNA analysis
      made it possible to identify the familial disease-associated haplotype and
      demonstrated that MEN1 disease haplotype family history can be reconstructed even
      when one or more family members are deceased. Identification of MEN1 disease
      haplotype is helpful in the clinical management of patients and relatives in
      families without any mutation of the MEN1 gene. Genetic screening allows the
      identification of individuals who are at risk before the development of clinical
      symptoms, limiting invasive annual cancer surveillance only to genetically
      positive individuals and making it possible to avoid further clinical screenings
      in non-carriers.

PMID- 19092298
TI  - Generation and analysis of an androgen-responsive myoblast cell line indicates
      that androgens regulate myotube protein accretion.
AB  - Androgens have anabolic actions in skeletal muscle and could potentially act to:
      (a) increase proliferation of myoblasts; (b) delay differentiation to myotubes;
      and (c) induce protein accretion in post-proliferative myofibers. To identify the
      site of androgens action, we investigated the proliferative response of the C2C12
      mouse myoblast cell line to testosterone and dihydrotestosterone (DHT) treatment.
      Neither androgens affected cell proliferation after up to 7 days treatment, nor
      was there a synergistic effect of androgens on the proliferative response of
      C2C12 cells to IGF-I treatment. However, proliferating C2C12 cells expressed 0.1%
      of the level of androgen receptor (AR) mRNA found in adult mouse gastrocnemius
      muscle (p<0.01). Therefore, we generated mouse C2C12 myoblast cell lines stably
      transfected with the mouse AR cDNA driven by the SV40 promoter (C2C12-AR). C2C12
      AR cell proliferation, differentiation, and protein content were analyzed in
      response to androgen treatment. Our data demonstrated that androgen treatment
      does not alter either proliferation rate or differentiation rate of C2C12-AR
      cells. However, treatment of differentiated C2C12-AR myotubes with 100 nM DHT for
      3 days caused a 20% increase in total protein content vs vehicle treatment
      (p<0.05). This effect was not observed in control C2C12 cells transfected with
      empty vector. These data suggest that androgens act via the AR to upregulate
      myotube protein content. This model cell line will be useful to further
      investigate the molecular mechanisms via which androgens regulate protein
      accretion.

PMID- 19092299
TI  - The management of the patient with acromegaly and headache: a still open clinical
      challenge.

PMID- 19092300
TI  - Cardiovascular aspects of primary hyperparathyroidism.
AB  - Data concerning the cardiovascular manifestations of primary hyperparathyroidism
      (PHPT) are inconsistent, which is due, in part, to the decrease in disease
      severity over the last several decades. In areas where patients tend to be more
      symptomatic, data support the presence of cardiovascular findings including
      myocardial and vascular calcification as well as increased cardiovascular
      mortality. Data from the cohorts in whom the disease is characterized by mild
      hypercalcemia, suggest that clinically overt cardiovascular manifestations are
      unusual in PHPT. Recent data, however, support the presence of subtle
      cardiovascular manifestations in mild disease, such as changes in endothelial
      function as well as increased vascular stiffness and perhaps diastolic
      dysfunction. Left ventricular hypertrophy is a more consistent finding across a
      spectrum of disease severity, though this finding may be related to hypertension,
      which has long been associated with PHPT.

PMID- 19092302
TI  - Improving the diagnosis of central hypothyroidism.

PMID- 19092301
TI  - Effects of endurance exercise on the reproductive system of men: the "exercise
      hypogonadal male condition".
AB  - An increasing number of investigative research studies point to participation in
      endurance exercise training as having significant detrimental effects upon
      reproductive hormonal profiles in men. Specifically, men chronically exposed to
      this type of exercise training exhibit persistently reduced basal (resting-state)
      free and total testosterone concentrations without concurrent LH elevations. Men
      displaying these symptoms have been deemed to exhibit the "exercise-hypogonadal
      male condition". The exact physiological mechanism inducing the reduction of
      testosterone in these men is currently unclear, but is postulated to be a
      dysfunction (or perhaps a readjustment) within the hypothalamic-pituitary
      testicular regulatory axis. The potential exists for the reduced testosterone
      concentrations within exercise-hypogonadal men to be disruptive and detrimental
      to some anabolic-androgenic testosterone- dependent physiological processes.
      Findings on this point are limited, but do suggest spermatogenesis problems may
      exist in some cases. Alternatively, reductions in circulating testosterone
      concentrations could have cardiovascular protective effects and thus be
      beneficial to the health of these men. Present evidence suggests the exercise
      hypogonadal condition is limited to men who have been persistently involved in
      chronic endurance exercise training for an extended period time (i.e., years),
      and it is not a highly prevalent occurrence (although, a thorough epidemiological
      investigation on the topic is lacking in the literature). Many questions
      regarding the male reproductive endocrine adaptive process to exercise training
      still remain unanswered, necessitating the need for much further investigation on
      the topic, especially with respect to the exercise-hypogonadal condition.

PMID- 19092303
TI  - Polycythemia as the first manifestation of Cushing's disease.

PMID- 19092304
TI  - An early description of Klinefelter syndrome at the beginning of the 20th century
      by Spyridon Livadas, an officer of the Medical Corps of the Hellenic Navy.

PMID- 19092311
TI  - Neuroimaging and geriatric psychiatry: the story of an interdisciplinary science
      and mental illness in the elderly.

PMID- 19092312
TI  - The Montgomery-Asberg Depression Rating Scale and the Cornell Scale for
      Depression in Dementia: a validation study with patients exhibiting early-onset
      dementia.
AB  - OBJECTIVE: To investigate some validity measures of Montgomery-Asberg Depression
      Rating Scale (MADRS) and Cornell Scale for Depression in Dementia (CSDD) in
      patients with early-onset dementia (EOD). DESIGN: Cross-sectional design.
      SETTING: Nursing home. PARTICIPANTS: A sample of 63 inpatients with EOD.
      MEASUREMENTS: Participants were assessed for the presence of clinical depression
      using the Provisional Diagnostic Criteria for Depression in Alzheimer Disease.
      Caregivers were administered the MADRS and CSDD, and two subscales from the
      Neuropsychiatric Inventory (NPI). RESULTS: Depressed patients had higher scores
      on 6 of the 10 MADRS items and on 3 of the 19 CSDD items than nondepressed
      patients. Receiver operating characteristic curve analysis revealed a larger area
      under the curve for MADRS (0.87) than for CSDD (0.76), the difference was
      significant (p = 0.044). A CSDD optimal cutoff score of "5/6" yielded a
      sensitivity of 0.833 and a specificity of 0.567. A MADRS cutoff score of "19/20"
      yielded the highest sum of sensitivity (0.750) and specificity (0.843). A MADRS
      score of "14/15" with almost the same sum of sensitivity and specificity had a
      higher sum of sensitivity and a negative predictive value than "19/20." Both
      scales correlated with the NPI subscales depression/dysphoria (MADRS: rs = 0.70;
      CSDD: rs = 0.62) and apathy/indifference (MADRS: rs = 0.59; CSDD: rs = 0.50).
      CONCLUSION: The MADRS and CSDD performed well in distinguishing depressed from
      nondepressed EOD patients and showed good congruent validity. The scales may be
      used to assess depressive symptoms in EOD. The MADRS intensity grades may be used
      for development or refinement of depression scales in (early onset) dementia.

PMID- 19092313
TI  - Willingness to participate in Alzheimer disease research and attitudes towards
      proxy-informed consent: results from the Health and Retirement Study.
AB  - OBJECTIVES: To evaluate public opinion about participation in Alzheimer disease
      (AD) research and willingness to have a proxy-informed consent. DESIGN: Cross
      sectional. SETTING: A national survey of community-dwelling adults over the age
      of 50 and their spouse of any age. PARTICIPANTS: The 2006 wave of the Health and
      Retirement Study (N = 1,517). MEASUREMENTS: Willingness to participate in one of
      four possible research scenarios and to have a proxy-informed consent for AD
      research. RESULTS: Overall, 65.8% agreed to participate in AD research and 70.7%
      agreed to proxy-informed consent. Relative to a minimal benefit and moderate risk
      scenario, participants were more likely to favor participation in a moderate
      benefit and minimal risk scenario and less likely to endorse a minimal benefit
      and severe risk scenario. Those agreeing to participate in the study were more
      likely to agree to proxy consent and to give leeway to a research proxy to go
      against their will. CONCLUSIONS: Most participants view AD research favorably and
      are agreeable toward participating in such research as well as toward having a
      research proxy. Participants are able to distinguish between studies of different
      levels of benefit and risk. Nevertheless, over 50% agreed to a study of minimal
      benefit and severe risk. Researchers and clinicians should be aware that those
      less agreeable toward AD research are less interested in having a research proxy.

PMID- 19092314
TI  - Incidence and documentation of cognitive impairment among older adults with
      severe mental illness in a community mental health setting.
AB  - OBJECTIVE: Cognitive impairments among older adults are commonly linked to poor
      medical and psychiatric treatment adherence, increased disability, and poor
      health outcomes. Recent investigations suggest that cognitive impairments are
      frequently not recognized by healthcare providers and are often poorly documented
      in medical records. Older adults utilizing services at community mental health
      centers have numerous risk factors for developing cognitive impairment. Few
      studies have explored the incidence and documentation of cognitive impairments in
      this patient population. METHODS: Data were collected from 52 ethnically diverse
      older adults with severe mental illness who were participating in treatment at a
      large community mental health center. Cognitive impairment was diagnosed by
      neuropsychologists utilizing the Mattis Dementia Rating Scale-2 (DRS). Measures
      of depression severity and substance abuse history were also obtained. An age and
      education corrected DRS total score falling at or below the tenth percentile was
      used as the criteria for diagnosing cognitive impairment. A medical chart review
      was subsequently conducted to determine the documentation of cognitive
      impairments among this patient population. RESULTS: Cognitive impairment was
      exhibited by 60% of participants and documented in medical charts for 17% of the
      sample. CONCLUSIONS: Preliminary data suggests that cognitive impairment is
      common in individuals with severe mental illness treated at community mental
      health centers, but these cognitive impairments are not well recognized or
      documented. The impact of cognitive impairment on psychiatric treatment and case
      management among community mental health patients is therefore poorly understood.

PMID- 19092316
TI  - Daily exercise fluctuations and dietary patterns during training predict visceral
      fat regain in obese women.
AB  - BACKGROUND: Visceral adiposity is an essential component of metabolic syndrome.
      Reduction of excessive visceral fat prevents metabolic syndrome and improves
      atherosclerotic diseases. This study aimed to identify dietary patterns and
      physical exercise during the training-education period that predict visceral
      adiposity regain during the follow-up period. METHODS: One hundred one moderately
      obese Japanese women, 23 to 67 years of age, participated in 0- to 4-month
      training-education and 12-month follow-up periods. Dietary patterns of food
      groups during training-education were analyzed by principal components analysis,
      and 3 major dietary patterns were derived. The change in visceral fat over the
      follow-up, adjusted for 4-month visceral fat area (VFA) and 4- to 16-month body
      mass index change, was analyzed using stepwise multiple linear regression.
      RESULTS: VFA and body weight decreased during training-education (P<0.001) and
      were maintained during follow-up. One major dietary pattern (of 3) (P=0.030) and
      standard deviations of daily exercise duration (P=0.012) during training
      education predicted VFA regain during follow-up. This regain correlated
      negatively with combinations of bread, milk and dairy products, fruits, seeds and
      nuts, and mushrooms, but positively with combinations of rice, pickles, miso,
      alcohol, and meat. The large standard deviation of daily exercise duration during
      training-education showed greater VFA regain during follow-up than did the
      smaller standard deviation (P=0.023), but body mass index did not show a similar
      trend. CONCLUSION: Our results revealed that daily exercise fluctuations and
      dietary patterns were useful predictors of visceral fat regain.

PMID- 19092317
TI  - Migraine-patent foramen ovale connection: role of prominent eustachian valve and
      large Chiari network in migrainous patients.
AB  - BACKGROUND: We postulated that eustachian valve (EV) and Chiari network (CN) play
      a role in the pathophysiology of both migraine and paradoxical embolism. We
      sought to prospectively investigate the potential role of EV/CN in migraine
      patent foramen ovale (PFO) connection assessing their prevalence by intracardiac
      echocardiography (ICE) in patients with migraine submitted to PFO transcatheter
      closure. METHODS: Over a 24-month period, we prospectively enrolled 50
      consecutive patients (mean age 37+/-12.5 years, 38 females) with previous stroke
      and migraine referred to our centre for PFO catheter-based closure. Migraine with
      aura (MwA) and migraine without aura (MwoA) were diagnosed according to the
      International Headache Society criteria and Migraine Disability Assessment Score
      (MIDAS). Patients who met the inclusion criteria for closure underwent ICE study
      and closure attempt. RESULTS: After ICE study, a prominent EV or CN were
      diagnosed on ICE in 41 patients (82%): 100% in MwA patients, 60% in MwoA patients
      (p<0.001) and in 55.5% of patients with no migraine. Patients with EV and CN had
      more frequently a curtain pattern on TC Doppler, a larger right-to-left shunt,
      more recurrent cerebral paradoxical embolism before closure, and a higher
      preoperative MIDAS score. Patients with EV/CN had a larger decrease in MIDAS
      score after closure. CONCLUSIONS: This study suggests that EV and CN have a deep
      impact on MwA and paradoxical embolism pathophysiology: EV, CN, and MwA should be
      considered as adjunctive risk factors for paradoxical embolism in the work-up of
      both symptomatic and asymptomatic PFO patients.

PMID- 19092318
TI  - Association of hydrophilic versus lipophilic angiotensin-converting enzyme
      inhibitor use on pneumonia-related mortality.
AB  - BACKGROUND: Recent studies suggest that angiotensin-converting enzyme (ACE)
      inhibitors may have beneficial effects for patients with or at risk for
      pneumonia. However, other studies have not found a survival benefit. Other
      research suggests that ACE inhibitors that are lipophilic may be superior to
      hydrophilic ACE inhibitors in terms of tissue penetration and inhibition of ACE.
      Our aim was to examine the associations of prior outpatient use of lipophilic and
      hydrophilic ACE inhibitors on mortality for patients hospitalized with community
      acquired pneumonia. METHODS: A retrospective cohort study of subjects
      hospitalized with pneumonia at 2 tertiary teaching hospitals. We examined whether
      the prior outpatient use of hydrophilic or lipophilic ACE inhibitors was
      associated with 30-day mortality in a logistic regression analysis that adjusted
      for potential confounders using a propensity score. RESULTS: Data were abstracted
      on 787 subjects at the 2 hospitals. In our cohort, 24% (n=186) were on ACE
      inhibitors at presentation: 111 lipophilic and 74 hydrophilic. Mortality was 9.2%
      at 30 days. In the multivariable model, lipophilic ACE inhibitor use (odds ratio
      0.3, 95% confidence interval 0.1-0.8), but not hydrophilic ACE inhibitor use
      (0.7, 0.3-1.7), was significantly associated with 30-day mortality. CONCLUSIONS:
      Our study suggests that future research of ACE inhibitors in pneumonia must
      describe the specific medications received. Confirmatory studies are needed, as
      well as research to determine the mechanism(s) of this protective effect.

PMID- 19092319
TI  - Stress-induced hyperglycemia in patients with severe sepsis: a compromising
      factor for survival.
AB  - OBJECTIVE: To study the clinical and laboratory characteristics of patients with
      severe sepsis and baseline hyperglycemia and investigate the impact of
      hyperglycemia on the final outcome. PATIENTS: A total of 265 patients admitted
      with severe sepsis in 3 major hospitals in South-Western Greece, during a 1-year
      period, were included in the study. Patients were divided in 3 groups according
      to their glycemic profile at admission: patients with stress hyperglycemia (group
      SH, n=47), with diabetes mellitus (group DM, n=65), and with normal glucose level
      (group NG, n=153). Hyperglycemia was defined as an admission or in-hospital
      fasting glucose level of >or=126 mg/dL or a random blood glucose level of >or=200
      mg/dL on >or=2 determinations. RESULTS: A total of 42.2% of patients with severe
      sepsis had baseline hyperglycemia with 17.7% having sepsis-induced stress
      hyperglycemia. No family history was noted in the SH group. A higher percentage
      of septic patients with stress hyperglycemia died compared with patients with
      normal glucose levels (42.5% versus 13.7%) and diabetics (42.5% versus 24.6%).
      Group DM had also a poorer prognosis than group NG (24.6% versus 13.7%). A
      positive correlation was detected between the fasting blood glucose levels of
      group SH and the severity of sepsis indicated by sepsis-related organ failure
      assessment score. CONCLUSION: Baseline hyperglycemia, including stress-induced
      hyperglycemia, is common in patients with severe sepsis. Stress-induced
      hyperglycemia is related to a more severe disease and poorer prognosis.

PMID- 19092320
TI  - Fat embolism syndrome.
AB  - OBJECTIVES: To assess the incidence and risk factors for fat embolism syndrome.
      MATERIALS AND METHODS: Data from the National Hospital Discharge Survey (NHDS)
      were analyzed using International Classification of Diseases, Ninth Revision,
      Clinical Modification (ICD-9-CM) codes. RESULTS: From 1979 through 2005 among
      928,324,000 patients discharged from short-stay hospitals in the United States,
      41,000 (0.004%) had fat embolism syndrome. Among 21,538,000 patients with an
      isolated fracture of the femur (any site), tibia, fibula, pelvis, ribs, humerus,
      radius, or ulna, 25,000 (0.12%) developed fat embolism syndrome. Patients with
      multiple fractures of the femur (excluding neck) more often had fat embolism
      syndrome than those with isolated fractures (1.29% versus 0.54%). The incidence
      of fat embolism syndrome was lower with isolated fractures of the tibia or fibula
      (0.30%) and even lower with isolated fractures of the neck of the femur (0.06%).
      The incidence of fat embolism was too low to calculate with isolated fractures of
      the pelvis, ribs, humerus, radius, or ulna. Nonorthopedic conditions rarely, if
      ever, were accompanied by fat embolism syndrome. The fat embolism syndrome was
      more frequent in men (relative risk 5.71). Children, aged 0 to 9 years rarely had
      fat embolism syndrome. The fat embolism syndrome most commonly affected patients
      aged 10 to 39 years. CONCLUSIONS: The incidence of the fat embolism syndrome
      depends on the bone involved, whether fractures are isolated or multiple, the age
      of the patient and the gender. It rarely occurs as a result of medical
      conditions.

PMID- 19092321
TI  - Small cell (neuroendocrine) carcinoma of the prostate: etiology, diagnosis,
      prognosis, and therapeutic implications--a retrospective study of 30 patients
      from the rare cancer network.
AB  - Within the framework of the Rare Cancer Network Study, we examined 30 patients
      suffering from small cell neuroendocrine prostate cancer, either in an
      early/localized or an advanced/metastatic stage. Patients were treated with
      cisplatin-based chemotherapy, with or without pelvic radiotherapy. Two patients
      with early disease achieved complete remission for a duration of 19 and 22
      months. Three patients with advanced disease achieved complete remission for 6,
      7, and 54 months, respectively. Twenty-five patients succumbed to massive local
      and/or distant failure. No patient presented with brain metastases as the initial
      site of relapse. Small cell neuroendocrine prostate carcinoma is a very
      aggressive disease with a poor prognosis, even in its localized form. Despite
      initial response, the common cisplatin-based chemotherapy plus radiotherapy
      failed to improve outcome markedly. Improvement will come from understanding the
      biology of the disease and integrating new targeted therapies into the treatment
      of this rare and aggressive tumor.

PMID- 19092322
TI  - Causes and consequences of systemic venous hypertension.
AB  - The causes of systemic venous hypertension (SVHT) include cardiac- and
      circulatory-related factors, whereas its consequences include the congestion of
      hepatic, splanchnic, and peripheral circulations, which contribute significantly
      to the clinical congestive heart failure syndrome. Based on a disequilibrium in
      hydrostatic and oncotic pressures, the increased filtration and formation of
      interstitial fluid at these sites with an accompanying increase in lymph flow
      mandates an increment in lymphatic drainage to protect against such congestion
      and the appearance of edema and ascites. However, lymph flow via the thoracic
      duct into systemic veins is opposed by elevations in central venous pressure.
      Various management strategies have the potential to prevent and/or correct SVHT.
      The case of a 54-year-old man with a dilated cardiomyopathy who presented with
      decompensated biventricular failure, expressed as anasarca and ascites, is used
      to illustrate the importance of SVHT.

PMID- 19092323
TI  - Scintographic evidence of severe myocardial hypoperfusion in a patient with left
      anterior descending coronary artery bridging--case report and review of the
      literature.
AB  - Myocardial bridging is a congenital abnormality characterized by an
      intramyocardial course of a major epicardial coronary artery segment. Generally
      considered a benign condition, myocardial bridging has been associated with
      angina, acute myocardial infarction, and sudden death. Herein, we report a
      patient with an intramyocardial segment in the mid portion of the left anterior
      descending coronary artery with marked systolic compression. Single photon
      emission computed tomography with technetium-99m tetrofosmin done to evaluate an
      episode of chest pain showed a large predominantly fixed perfusion defect in the
      mid to apical anterior wall with partial reversibility. The patient's chest pain
      did not recur and repeat single photon emission computed tomography imaging 14
      days later with rest-redistribution thallium-201 showed normal myocardial
      perfusion. The overall clinical impression was that myocardial bridging resulted
      in severe transient anterior myocardial hypoperfusion. The literature on
      prevalence, diagnosis, use of perfusion imaging, and hemodynamic effects of
      myocardial bridging is reviewed.

PMID- 19092324
TI  - Brain stem and clivus plasmacytoma.

PMID- 19092325
TI  - Gas-forming parotid abscess in a diabetic patient: an unusual complication of
      Salmonella enteritidis bacteremia.
AB  - Parotid abscess, not only a focal infection but also a sequela of systemic
      infection, necessitates the detailed search for the underlying pathogens. A 76
      year-old diabetic male visited the emergency room of a hospital because of
      intermittently low-grade fever and a painful lump in the right parotid gland
      region for 7 days. Progressive painful swelling of the gland with the signs of
      severe sepsis developed 3 days later. Computed tomography of the neck revealed a
      cavitary lesion with an air-fluid level in the right parotid space. Superficial
      parotidectomy was performed. Salmonella enteritidis was isolated from both the
      pus and the blood culture. After a 2-week course of intravenous ampicillin and an
      additional 2-week course of oral moxifloxacin, he was free from recurrence at a 6
      month follow-up. This case highlights that an initially nontoxic parotitis may be
      the presenting feature of extraintestinal salmonellosis. Early diagnosis and
      treatment are important to prevent lethal dissemination in high-risk groups.

PMID- 19092326
TI  - Fever of unclear origin and cytopenia because of acute splenic sequestration in a
      young immunocompetent carrier of beta-globin mutation for Hb Valletta.
AB  - Fever of unclear origin is a clinical challenge in medical practice. Infectious
      diseases, neoplasms, and collagen vascular illnesses are its main causes in
      adults and children. Acute splenic sequestration crises, a known potentially
      fatal complication of sickle cell disease and sickle beta-thalassemia, are
      uncommon in beta-heterozygosis. We describe a case of prolonged recurrent
      episodes of fever with spontaneous resolution, commencing at age 10 in a 15-year
      old boy with a history of hypochromic microcytic anemia attributed to a
      thalassemic trait. He was admitted twice to our university hospital for
      continuous-remittent fever with a pruritic, macular evanescent Still's skin rash,
      severe splenomegaly, leucopenia, thrombocytopenia, and sudden aggravation of
      anemia. Infectious, rheumatologic, autoimmune, and hematologic illnesses were
      excluded. A genetic-based study revealed heterozygosis of the beta-globin gene
      for a A>C (Thr>Pro) substitution at position 87 called Hemoglobin Valletta (alpha
      2 beta 2 87 PRO) with a C>G transition in homozygosis in beta-globin intronic
      polymorphism intervening sequence 2 at nucleotide 745. After a follow-up period
      of 1 year without treatment, the young patient remains apyretic and in good
      general clinical health with persistent microcythemia and hepatosplenomegaly.
      Acute splenic sequestration crisis and related cytopenia may be an unusual
      complication of fever of unclear origin in a beta-thalassemic carrier of a
      Hemoglobin Valletta mutation and polymorphism in homozygosis of intervening
      sequence 2 at nucleotide 745. This hemoglobinopathy may predispose to a clinical
      phenotype of minor or intermediate thalassemia and, during a febrile illness, to
      hemoglobin instability and splenic sequestration.

PMID- 19092327
TI  - Acute renal failure after exercise in a Japanese sumo wrestler with renal
      hypouricemia.
AB  - Familial renal hypouricemia is a hereditary disease characterized by
      extraordinary high renal uric acid clearance and is associated with acute renal
      failure (ARF). An 18-year-old sumo wrestler developed ARF after anaerobic
      exercise. Several hours after the exercise, he had a pain in the loins with
      oliguria, headache, and nausea. On admission, his serum uric acid was decreased
      despite the elevation of serum creatinine (9.5 mg/dL). The level of creatine
      kinase was normal and there was no myoglobinuria or urolithiasis. Magnetic
      resonance imaging showed no significant abnormality. Renal function improved
      completely within 2 weeks of hydration treatment. After remission, hypouricemia
      became obvious (1.0 mg/dL) from the initial level of uric acid (6.1 mg/dL) and
      fractional excretion of uric acid was 49%. Polymerase chain reaction of a urate
      anion exchanger known to regulate blood urate level (SLC22A12 gene: URAT1)
      demonstrated that homozygous mutations in exon 4 (W258X). Both parents showed
      heterozygous mutation of the URAT1 gene, but both siblings showed no mutation.
      Thus, we describe a Japanese sumo wrestler of familial renal hypouricemia
      complicated with anaerobic exercise-induced ARF, with definite demonstration of
      genetic abnormality in the responsible gene, URAT1.

PMID- 19092328
TI  - Hepatitis C infection and thyrotoxic periodic paralysis--a novel use of an old
      drug.
AB  - Hypokalaemic thyrotoxic periodic paralysis is an enigmatic and uncommon condition
      which occurs exclusively in males of Asian descent. The underlying causes of
      thyrotoxicosis may be any of the well-recognized etiologies including a toxic
      multinodular goiter, Graves' disease or iodine excess. Beside thyrotoxicosis, a
      number of other hormonal factors have been hypothesized to contribute to
      hypokalaemic thyrotoxic periodic paralysis, particularly postprandial
      hyperinsulinaemia and testosterone. We hereby present a case of a 48-year-old
      hepatitis C positive gender-assigned man in whom all of these factors are
      proposed to interact, lending further support to these hypotheses. The patient
      presented with interferon-induced thyroiditis causing acute generalized weakness
      whilst undergoing combination interferon-alpha-2beta and ribavirin therapy. As
      part of his hepatitis C infection, marked insulin resistance with
      hyperinsulinaemia was also present, exacerbating the paresis. Initial treatment
      with beta-blocker failed to normalize his serum potassium concentration,
      requiring the novel use of spironolactone, despite euthyroidism. This continued
      to be required until his testosterone supplement dissipated.

PMID- 19092329
TI  - A patient with Creutzfeldt-Jakob disease with an insertion of 7 octa-repeats in
      the PRNP gene: molecular characteristics and clinical features.
AB  - BACKGROUND: We evaluated the features of neuropathology, abnormal prion protein
      (PrP) molecules, and clinical data of a Chinese woman diagnosed with familiar
      Creutzfeldt-Jakob disease (CJD), having 7 octa-repeats inserted with codon 129
      methionine homozygote in the PRNP gene. METHODS: Neuropathologic characteristics
      of the brain were analyzed by hemotoxylin-eosin stain and electronic microscopy.
      The presence of abnormal PrP in brains was detected by proteinase K and PrP
      molecules were evaluated by deglycosylation assay. RESULTS: Spongiform
      degeneration, with diffuse neuronal loss and mild astrocytic gliosis, as well as
      with profound degeneration of neurons and astrocytes was observed. Proteinase K
      resistant PrP was deposited widely in various regions of the brain. Calculation
      of the glycosylation ratios of proteinase K-resistant PrP molecules identified
      that the monoglycosyl isomer was predominant. PrP deglycosylation tests allowed
      for the identification of a predominant 19-kDa PrP signal that represents a
      partially proteolytic C-terminal segment, a 27-kDa band that represents the full
      length wild-type PrP molecule, and a 30-kDa band that probably corresponds to the
      full-length mutant PrP molecule. CONCLUSION: : Sporadic CJD-like neuropathologic
      changes and deposits of proteinase K-resistant PrP have been identified in this
      familiar CJD case with a 168 base pair nucleotide insertion. The clinical
      features differ from previously reported cases that had 7 octa-repeat insertion,
      but bear similarities to sporadic CJD.

PMID- 19092330
TI  - A mistaken diagnosis of type 2 diabetes due to hemoglobin N-Baltimore.
AB  - Glycohemoglobin (HbA1c) estimation is the gold standard for assessing long-term
      glycemic control in diabetic patients. Some hemoglobin variants interfere with
      HbA1c assay, thus, limiting its utility. Over 150,000 diabetic patients are
      estimated to have hemoglobin variants in the United States; but this number may
      be up to 30% in some parts of the world. Although, most of the hemoglobinopathies
      are clinically silent, some of them cause biochemical aberrations, which could
      interfere with HbA1c assay. However, hemoglobin N-Baltimore has not been reported
      to give false HbA1c estimation. We present a woman with mistaken diagnosis of
      diabetes due to hemoglobin N-Baltimore that produced a spuriously elevated HbA1c
      level.

PMID- 19092331
TI  - Pulmonary arteriovenous malformation associated with necrotizing fasciitis of the
      thigh.
AB  - Pulmonary arteriovenous malformation (PAVM) is a rare condition often associated
      with hereditary hemorrhagic telangiectasia. The association between PAVMs and
      brain abscesses has been previously reported, but abscesses at other locations
      are extremely rare. We present a 51-year-old woman with PAVM (without signs of
      hereditary hemorrhagic telangiectasia) and necrotizing fasciitis of her thigh and
      discuss the possible relationship between the 2 disorders.

PMID- 19092332
TI  - Chronic dyspnea and severe obstruction after pneumonectomy: postpneumonectomy
      syndrome.
AB  - Postpneumonectomy syndrome is a rare complication secondary to postsurgical
      anatomic changes in the pneumonectomy space. Patients present with marked dyspnea
      on exertion secondary to airflow limitation from proximal airway compression and
      overdistention of the remaining lung because of mediastinal shift.
      Postpneumonectomy syndrome is treated by surgical repositioning of the
      mediastinum. Knowledge of the clinical and radiological features will enable
      prompt diagnosis and appropriate treatment.

PMID- 19092333
TI  - Ambition... and humility of the surgeons.

PMID- 19092334
TI  - Response evaluation by endoscopy, rebiopsy, and endoscopic ultrasound does not
      accurately predict histopathologic regression after neoadjuvant chemoradiation
      for esophageal cancer.
AB  - OBJECTIVE: To prospectively assess the sensitivity (sens), specificity (spec),
      positive predictive value (ppv), negative predictive value (npv), and accuracy
      (acc) for clinical response evaluation by endoscopy, rebiopsy, and endoscopic
      ultrasound (EUS) to determine histomorphologic regression UICC T-category
      downstaging after neoadjuvant chemoradiation for esophageal cancer. BACKGROUND:
      Histomorphologic regression is meanwhile established as objective parameter for
      response and prognosis after neoadjuvant chemoradiation for esophageal cancer.
      PATIENTS AND METHODS: Within a prospective observation trial, 80 patients with
      localized esophageal cancers (cT2-4,Nx,M0) received standardized neoadjuvant
      chemoradiation (cisplatin, 5-fluorouracil, 36 Gy) and were resected by
      transthoracic en bloc esophagectomy and two-field lymphadenectomy. Tumor
      regression was based on the percentage of vital residual tumor cells and
      classified in 4 categories as reported previously. Evaluation by endoscopy and
      EUS was performed based on WHO/UICC criteria before starting chemoradiation and
      before resection and rebiopsies were taken at the time of re-endoscopy. RESULTS:
      Histomorphologic response was of significant (log rank) prognostic importance (P
      < 0.001), whereas clinical response evaluation by endoscopy (P = 0.1), rebiopsy
      (P = 0.34), and EUS (P = 0.35) was not. The results of the 3 diagnostic
      modalities to assess histomorphologic regression by endoscopy and rebiopsy UICC
      ypT-category downstaging for EUS are summarized: Endoscopy: sens 60%, spec 34%,
      ppv 49%, npv 44%, acc 47%. Rebiopsy: sens 36%, spec 100%, ppv 100%, npv 24%, acc
      47%. EUS: sens 7%, spec 79%, ppv 18%, npv 57%, acc 50%. CONCLUSIONS:
      Histomorphologic regression is an objective response parameter of significant
      prognostic importance. The diagnostic accuracy of endoscopy, rebiopsy, and EUS is
      inadequate for objective response evaluation after neoadjuvant chemoradiation and
      can be omitted for this purpose in the clinical practice.

PMID- 19092335
TI  - A randomized controlled trial on pharmacological preconditioning in liver surgery
      using a volatile anesthetic.
AB  - OBJECTIVE: To evaluate the effects of pharmacological preconditioning with a
      volatile anesthetic in patients undergoing liver resection with inflow occlusion.
      BACKGROUND: In liver surgery, ischemic preconditioning and intermittent clamping
      are the only established protective strategies to reduce tissue damage due to
      ischemia during inflow occlusion. Preconditioning with volatile anesthetics has
      provided protection against cardiac and renal ischemic injury in several animal
      models through NO and HO-1 pathways. But pharmacological preconditioning has
      never been tested in patients undergoing liver surgery in a randomized trial.
      METHODS: Sixty-four patients undergoing liver surgery with inflow occlusion were
      randomized intraoperatively for preconditioning with sevoflurane or not
      (ClinicalTrials.gov NCT00516711). Anesthesia was performed intravenously with
      propofol. Thirty minutes before inflow occlusion propofol was replaced by
      sevoflurane in the preconditioning group. Primary endpoint was postoperative
      liver injury assessed by peak values of liver transaminases. Postoperative
      complications were recorded according to an established scoring system. RESULTS:
      Sevoflurane preconditioning significantly limited the postoperative increase of
      serum transaminase levels by 261 U/L (95% CI, 65 to 458; P = 0.01) for the ALT
      and by 239 (95% CI, -2 to 480; P = 0.05) for the AST corresponding to decreases
      of baseline levels of 35% and 31%, respectively. Patients with steatosis had an
      even better benefit than patients without steatosis. The rates of any
      complication (risk ratio 0.46; 95% CI, 0.25 to 0.85; P = 0.006) and of severe
      complications requiring invasive procedures (risk ratio 0.25; 95% CI, 0.06 to
      1.08; P = 0.05) were also lowered by preconditioning. CONCLUSION: This first
      randomized trial of pharmacological preconditioning in liver surgery in humans
      showed a protective effect of preconditioning with volatile anesthetics. This
      strategy may provide a new and easily applicable therapeutic option to protect
      the liver and to lower complication rates.

PMID- 19092336
TI  - Erythropoietin protects critically perfused flap tissue.
AB  - OBJECTIVE: The objective of this study was to analyze whether erythropoietin
      (EPO) protects from necrosis of critically perfused musculocutaneous tissue and
      the mechanisms by which this protection is achieved. BACKGROUND: EPO is the
      regulator of erythropoiesis and is used to treat patients with anemia of
      different causes. Recent studies suggest that EPO has also other tissue
      protective effects, irrespective of its erythropoietic properties. MATERIAL AND
      METHODS: C57BL/6-mice were treated with 3 doses of EPO at 500 IU/kg
      intraperitoneally. EPO was given either before (preconditioning, n = 7), before
      and after (overlapping treatment, n = 7), or after (treatment, n = 7) surgery.
      Animals receiving only saline served as controls (CON). Acute persistent ischemia
      was induced by elevating a randomly perfused flap in the back of the animals.
      This critically perfused tissue demonstrates an initial microvascular failure of
      approximately 40%, resulting in approximately 50% tissue necrosis if kept
      untreated. Repetitive fluorescence microscopy was performed over 10 days,
      assessing angiogenesis, functional capillary density, inflammatory leukocyte
      endothelial cell interaction, apoptotic cell death, and tissue necrosis.
      Additional molecular tissue analyses included the determination of inducible
      nitric oxide synthase, erythropoietin receptor (EPO-R), and vascular endothelial
      growth factor (VEGF). RESULTS: EPO preconditioning did not affect hematocrit and
      EPO-R expression, but increased inducible nitric oxide synthase in the critically
      perfused tissue. This correlated with a significant arteriolar dilation, which
      resulted in a maintained functional capillary density (CON: 0 +/- 0 cm/cm(2);
      preconditioning: 37 +/- 21 cm/cm(2); overlapping treatment: 72 +/- 26 cm/cm(2); P
      < 0.05). EPO pretreatment further significantly reduced microvascular leukocyte
      adhesion and apoptotic cell death. Moreover, EPO pretreatment induced an early
      VEGF upregulation, which resulted in new capillary network formation (CON: 0 +/-
      0 cm/cm(2); preconditioning: 40 +/- 3 cm/cm(2); overlapping treatment: 33 +/- 3
      cm/cm(2); P < 0.05). Accordingly, EPO pretreatment significantly reduced tissue
      necrosis (CON: 48% +/- 2%; preconditioning: 26% +/- 3%; overlapping treatment:
      20% +/- 3%; P < 0.05). Of interest, EPO treatment was only able to alleviate
      ischemia-induced inflammation but could not improve microvascular perfusion and
      tissue survival. CONCLUSIONS: EPO pretreatment improves survival of critically
      perfused tissue by nitric oxide -mediated arteriolar dilation, protection of
      capillary perfusion, and VEGF-initiated new blood vessel formation.

PMID- 19092337
TI  - Pancreatogastrostomy with gastric partition after pylorus-preserving
      pancreatoduodenectomy versus conventional pancreatojejunostomy: a prospective
      randomized study.
AB  - OBJECTIVE: To compare the results of postoperative morbidity rate of a new
      pancreatogastrostomy technique, pylorus-preserving pancreaticoduodenectomy (PPPD)
      with gastric partition (PPPD-GP) with the conventional technique of
      pancreaticojejunostomy (PJ). SUMMARY AND BACKGROUND DATA: Pancreatojejunostomy
      and pancreatogastrostomy (PG) are the commonly preferred methods of anastomosis
      after pancreatoduodenectomy (PD). All randomized controlled trials failed to show
      advantage of a particular technique, suggesting that both PJ and PG provide
      equally results. However, postoperative morbidity remains high. The best
      technique in pancreatic anastomosis is still debated. METHOD: Described here is a
      new technique, PPPD-GP; in this technique the gastroepiploic arcade is preserved.
      Gastric partition was performed using 2 endo-Gia staplers along the greater
      curvature of the stomach, 3 cm from the border. This gastric segment, 10 to 12 cm
      in length is placed in close proximity to the cut edge of the pancreatic stump.
      An end-to-side, duct-to-mucosa anastomosis (with pancreatic duct stent) is
      constructed. One hundred eight patients undergoing PPPD for benign and malignant
      diseases of the pancreatic head and the periampullary region were randomized to
      receive PG (PPPD-GP) or end-to-side PJ (PPPD-PJ). RESULTS: The two treatment
      groups showed no differences in preoperative parameters and intraoperative
      factors. The overall postoperative complications were 23% after PPPD-GP and 44%
      after PPPD-PJ (P < 0.01). The incidence of pancreatic fistula was 4% after PPPD
      GP and 18% after PPPD-PJ (P < 0.01). The mean + SD hospital stay was 12 +/- 2
      days after PPPD-GP and 16 +/- 3 days after PPPD-PJ. CONCLUSIONS: This study shows
      that PPPD-GP can be performed safely and is associated with less complication
      than PPPD-PJ. The advantage of this technique over other PG techniques is that
      the anastomosis is outside the area of the stomach where the contents empty into
      the jejunum, but pancreatic juice drains directly into the stomach.

PMID- 19092338
TI  - Improvement of vascularization of PLGA scaffolds by inosculation of in situ
      preformed functional blood vessels with the host microvasculature.
AB  - OBJECTIVE: We analyzed, in vivo, whether the establishment of blood supply to
      implanted scaffolds can be accelerated by inosculation of an in situ-preformed
      microvascular network with the host microvasculature. BACKGROUND: A rapid
      vascularization is crucial for the survival of scaffold-based transplanted tissue
      constructs. METHODS: Poly-lactic-glycolic acid scaffolds were implanted into the
      flank of balb/c or green fluorescent protein (GFP)-transgenic mice for 20 days to
      create in situ a new microvascular network within the scaffolds. The
      prevascularized scaffolds were then transferred into the dorsal skinfold chamber
      of isogeneic recipient mice. Nonvascularized poly-lactic-glycolic acid scaffolds
      served as controls. Vascularization, blood perfusion, and cell survival of the
      implants were analyzed over 14 days using intravital fluorescence microscopy,
      histology, and immunohistochemistry. RESULTS: Our results demonstrate that
      establishment of blood perfusion of prevascularized scaffolds is significantly
      accelerated and improved (136.7 +/- 23.2 pl/s) when compared with controls (6.9
      +/- 1.9 pl/s), because the in situ-preformed microvessels were reperfused by
      forming interconnections to the host microvasculature. Apoptotic cell death
      within the implants was found only during the first 3 to 6 days after scaffold
      implantation during lack of blood perfusion, but not during the further 14-day
      observation period. CONCLUSIONS: Inosculation of in situ-preformed functional
      blood vessels represents a promising approach to improve the blood supply to
      implanted tissue constructs.

PMID- 19092339
TI  - Sentinel node tumor burden according to the Rotterdam criteria is the most
      important prognostic factor for survival in melanoma patients: a multicenter
      study in 388 patients with positive sentinel nodes.
AB  - SUMMARY BACKGROUND DATA: The more intensive sentinel node (SN) pathologic workup,
      the higher the SN-positivity rate. This is characterized by an increased
      detection of cases with minimal tumor burden (SUB-micrometastasis <0.1 mm), which
      represents different biology. METHODS: The slides of positive SN from 3 major
      centers within the European Organization of Research and Treatment of Cancer
      (EORTC) Melanoma Group were reviewed and classified according to the Rotterdam
      Classification of SN Tumor Burden (<0.1 mm; 0.1-1 mm; >1 mm) maximum diameter of
      the largest metastasis. The predictive value for additional nodal metastases in
      the completion lymph node dissection (CLND) and disease outcome as disease-free
      survival (DFS) and overall survival (OS) was calculated. RESULTS: In 388 SN
      positive patients, with primary melanoma, median Breslow thickness was 4.00 mm;
      ulceration was present in 56%. Forty patients (10%) had metastases <0.1 mm.
      Additional nodal positivity was found in only 1 of 40 patients (3%). At a mean
      follow-up of 41 months, estimated OS at 5 years was 91% for metastasis <0.1 mm,
      61% for 0.1 to 1.0 mm, and 51% for >1.0 mm (P < 0.001). SN tumor burden increased
      significantly with tumor thickness. When the cut-off value for SUB
      micrometastases was taken at <0.2 mm (such as in breast cancer), the survival was
      89%, and 10% had additional non-SN nodal positivity. CONCLUSION: This large
      multicenter dataset establishes that patients with SUB-micrometastases <0.1 mm
      have the same prognosis as SN negative patients and can be spared a CLND. A <0.2
      mm cut-off for SUB-micrometastases does not seem correct for melanoma, as 10%
      additional nodal positivity is found.

PMID- 19092340
TI  - Tacrolimus monotherapy in liver transplantation: one-year results of a
      prospective, randomized, double-blind, placebo-controlled study.
AB  - BACKGROUND: Minimal immunosuppression (IS) is desirable in organ transplantation
      to reduce side effects and to promote the process of tolerance induction.
      MATERIAL AND METHODS: Between February 2000 and September 2004, 156 adults (>15
      years old) receiving a primary liver graft were enrolled in a prospective,
      randomized, double-blind, placebo-controlled, investigator-driven single-center
      study comparing tacrolimus (TAC)-placebo (PL) and TAC-low-dose, short-term (64
      days) steroid (ST) IS. There were no exclusion criteria at moment of
      randomization. All patients had a 12-month follow-up (range, 12-84). RESULTS:
      Three- and 12-month patient survival rates were 93.6% and 87.2% in the TAC-PL
      group and 98.7% and 94.7% in TAC-ST group (P = 0.096 and P = 0.093,
      respectively). Three- and 12-month graft survival rates were 92.3% and 85.9%
      versus 97.4% and 92.3% (P = 0.14 and 0.13, respectively). By 3 and 12 months,
      rejection treatment had been given in 20.5% (16 pts) and 23% (18 pts) of TAC-PL
      patients and in 12.7% (10 pts) and 20.5% (16 pts) of TAC-ST patients (P = 0.20
      and 0.54). Corticosteroid-resistant rejection (CRR) at 3 and 12 months was
      recorded in 12.8% (10 pts) of TAC-PL patients and 3.8% (3 pts) of TAC-ST patients
      (P = 0.04). When considering the 145 patients transplanted without artificial
      organ support (n = 145), CRR at 3 and 12 months was recorded in 8.8% (6/68 pts)
      of TAC-PL patients and in 3.9% (3/77 pts) of TAC-ST patients (P = 0.22).
      Vanishing bile duct syndrome was diagnosed in 1 (1.2%) TAC-PL patient and 4
      (5.1%) TAC-ST patients (P = 0.17). By 1 year, 78.2% (61/78) of TAC-PL patients
      and 82% (64/78) of TAC-ST patients were on TAC monotherapy (P = 0.54). When
      considering 67 TAC-PL and 74 TAC-ST survivors, rates of monotherapy were 91% (61
      pts) and 86.5% (64 pts) (P = 0.39). At 1 year, 62.5% (42 pts) of TAC-PL survivors
      and 64.9% (48 pts) of TAC-ST survivors were on low-dosage (<6 ng/mL) TAC
      monotherapy (P 0.79). CONCLUSION: TAC monotherapy can be achieved safely without
      compromising graft nor patient survival in a primary, even unselected, adult
      liver transplant population. The higher incidence of early CRR in the TAC-PL
      group related to the significantly higher number of patients transplanted while
      being on artificial organ support. In such condition, this monodrug
      immunosuppressive strategy needs to be adapted. TAC monotherapy strategy should
      lay the basis for further large scale minimization studies in liver
      transplantation.

PMID- 19092341
TI  - Prognosis of patients with colorectal cancer is associated with lymph node ratio:
      a single-center analysis of 3,026 patients over a 25-year time period.
AB  - OBJECTIVE: We examined the prognostic impact of lymph node ratio (relation of
      tumor-infiltrated to resected lymph nodes) in comparison to the pN category and
      other prognostic factors in patients with colorectal cancer. SUMMARY BACKGROUND
      DATA: Although the high prognostic impact of lymph node metastases and the total
      number of lymph nodes to be resected are well established, studies still report
      large differences in lymph node numbers. The lymph node ratios relevant for
      prognosis are not clearly defined and not routinely reported. METHODS: We
      analyzed the clinical and histopathological data of 3026 patients with colorectal
      cancer at a single surgical center over a 25-year time period (1982-2006).
      RESULTS: One thousand seven hundred sixty-three colon and 1263 rectal carcinomas
      were documented. The rate of curative resection was 77.4% and the median number
      of resected lymph nodes was 16. The optimal cut-off values for prognostic
      differentiation of LNRs were statistically calculated as 0.17, 0.41, and 0.69.
      The 5-year overall survival of patients without lymph node metastases was 87%.
      Patients with lymph node metastases had 5-year overall survival rates of 60.6%,
      34.4%, 17.6%, and 5.3% with increasing LNRs (P < 0.001). Multivariate survival
      analysis identified both the LNR and the pN category, the number of resected
      lymph nodes, the patient's age, the tumor location (colon vs. rectum), the pT
      category, the pM status, the R status, the tumor grade, and the year of operation
      as independent prognostic factors. The LNR had better prognostic value than the
      pN category (P < 0.05). The analysis of the subgroup of patients separated into
      colon and rectal cancer patients confirmed the identified LNRs as independent
      prognostic factors (P < 0.001). CONCLUSIONS: The defined cut-off values of LNRs
      were strong independent prognostic factors for colorectal cancer patients and
      should be calculated for risk group stratification.

PMID- 19092342
TI  - Predicting systemic disease in patients with esophageal cancer after
      esophagectomy: a multinational study on the significance of the number of
      involved lymph nodes.
AB  - OBJECTIVE: The aim of this study was to determine whether the risk of systemic
      disease after esophagectomy can be predicted by the number of involved lymph
      nodes. SUMMARY BACKGROUND DATA: Primary esophagectomy is curative in some but not
      all patients with esophageal cancer. Identification of patients at high risk for
      systemic disease would allow selective use of additional systemic therapy. This
      study is a multinational, retrospective review of patients treated with resection
      alone to assess the impact of the number of involved lymph nodes on the
      probability of systemic disease. METHODS: The study population included 1,053
      patients with esophageal cancer (700 adenocarcinoma, 353 squamous carcinoma) who
      underwent R0 esophagectomy with > or =15 lymph nodes resected at 9 international
      centers: Asia (1), Europe (5), and United States (3). To ensure a minimum
      potential follow-up of 5 years, only patients who had esophagectomy before
      October 2002 were included. Patients treated with neoadjuvant or adjuvant therapy
      were excluded. The impact of the number of involved lymph nodes on the risk of
      systemic disease recurrence was assessed using univariate and multivariate
      analyses. RESULTS: Systemic disease occurred in 40%. The number of involved lymph
      nodes ranged from 0 to 26 with 55% of patients having at least 1 involved lymph
      node. The frequency of systemic disease after esophagectomy was 16% for those
      without nodal involvement and progressively increased to 93% in patients with 8
      or more involved lymph nodes. CONCLUSIONS: This study shows that the number of
      involved lymph nodes can be used to predict the likelihood of systemic disease in
      patients with esophageal cancer. The probability of systemic disease exceeds 50%
      when 3 or more nodes are involved and approaches 100% when the number of involved
      nodes is 8 or more. Additional therapy is warranted in these patients with a high
      probability of systemic disease.

PMID- 19092343
TI  - Four hundred laparoscopic myotomies for esophageal achalasia: a single centre
      experience.
AB  - OBJECTIVE: Laparoscopic myotomy is the currently preferred treatment for
      achalasia. Our objectives were to assess the long-term outcome of this operation
      and preoperative factors influencing said outcome. METHODS: Demographic and
      clinical characteristics and data on long-term outcome were prospectively
      collected on patients undergoing laparoscopic myotomy for achalasia at our
      institution from 1992 to 2007. Treatment failure was defined as a postoperative
      symptom score higher than the 10th percentile of the preoperative score (>9).
      Logistic regression analysis was used to identify independent preoperative
      factors associated with successful myotomy. RESULTS: Four hundred seven
      consecutive patients (220 men, 187 women) underwent the laparoscopic Heller-Dor
      procedure during the study period; 89 (22%) of them had previously had endoscopic
      treatment(s). The mortality rate was 0; the conversion and morbidity rates were
      1.5% and 1.9%, respectively. The operation failed in 10% of patients (39/407) and
      the 5-year actuarial probability of being asymptomatic was 87%. Most failures
      (25/39, 64%) occurred within 12 months of the operation and can be considered as
      technical failures (incomplete myotomy). Pneumatic dilation overcome the
      dysphagia in 75% of patients whose surgery was unsuccessful. Considering both the
      primary surgery and this ancillary treatment, the operation was effective in 97%
      of achalasia patients. The frequency of sigmoid esophagus, lower esophageal
      sphincter (LES) resting pressures, and chest pain scores differed statistically
      between patients with and without recurrences. At multivariate analysis, high
      preoperative LES pressures (>30 mm Hg) was an independent predictor of a good
      response. The presence of chest pain and of sigmoid esophagus independently
      predicted the failure of the procedure. CONCLUSION: Laparoscopic myotomy can
      durably relieve dysphagia symptoms. High preoperative LES pressures represent the
      strongest predictor of a positive outcome, probably reflecting a less severely
      damaged esophageal muscle.

PMID- 19092344
TI  - Long-term results of two-stage hepatectomy for irresectable colorectal cancer
      liver metastases.
AB  - OBJECTIVE: To assess feasibility, risks, and long-term outcome of 2-stage
      hepatectomy as a means to improve resectability of colorectal liver metastases
      (CLM). SUMMARY BACKGROUND DATA: Two-stage hepatectomy uses compensatory liver
      regeneration after a first noncurative hepatectomy to enable a second curative
      resection. METHODS: Between October 1992 and January 2007, among 262 patients
      with initially irresectable CLM, 59 patients (23%) were planned for 2-stage
      hepatectomy. Patients were eligible when single resection could not achieve
      complete treatment, even in combination with chemotherapy, portal embolization,
      or radiofrequency, but tumors could be totally removed by 2 sequential
      resections. Feasibility and outcomes were prospectively evaluated. RESULTS: Two
      stage hepatectomy was feasible in 41 of 59 patients (69%). Eighteen patients
      failed to complete the second hepatectomy because of disease progression (n = 17)
      or bad performance status (n = 1). The 41 successfully treated patients had a
      mean number of 9.1 metastases (mean diameter, 48.5 mm at diagnosis). Chemotherapy
      was delivered before (95%), in between (78%), and after (78%) the 2
      hepatectomies. Mean delay between the 2 liver resections was 4.2 months.
      Postoperative mortality was 0% and 7% (3/41) after the first and second
      hepatectomy, respectively. Morbidity rates were also higher after the second
      procedure (59% vs. 20%) (P < 0.001). Five-year survival was 31% on an intention
      to treat basis, and all but 2 patients who did not complete the 2-stage strategy
      died within 19 months. After a median follow-up of 24.4 months (range, 3.7
      130.3), overall 3- and 5-year survivals for patients that completed both
      hepatectomies were 60% and 42%, respectively, after the first hepatectomy (median
      survival, 42 months from first hepatectomy and 57 months from metastases
      diagnosis). Disease-free survivals were 26% and 13% at 3 and 5 years,
      respectively. CONCLUSIONS: Two-stage hepatectomy provides a 5-year survival of
      42% and a hope of long-term survival for selected patients with extensive bilobar
      CLM, irresectable by any other means.

PMID- 19092345
TI  - Predicting individual survival after potentially curative esophagectomy for
      adenocarcinoma of the esophagus or gastroesophageal junction.
AB  - INTRODUCTION: Even after potentially curative esophagectomy, the majority of
      patients with adenocarcinoma of the esophagus or gastroesophageal junction die
      due to cancer recurrence. To predict individual disease-specific survival, a
      nomogram has been developed in a high-volume center in the Netherlands. The
      validity of this nomogram was externally tested in patients treated in another
      country at a different high-volume institution. METHODS: Clinicopathological data
      from patients who underwent a macroscopically radical resection in a high-volume
      center in Leuven, Belgium, were used to validate the original nomogram based on a
      Cox regression model. Moreover, it was examined whether adjusting the value of
      the original coefficients of the predictors or adding new predictors would
      improve the fit of the nomogram in the validation cohort. Calibration was
      evaluated by comparing the observed survival with the expected survival as
      predicted by the original nomogram across patients with different risk profiles.
      The discriminatory ability of the nomogram was determined in the validation
      cohort, using the concordance index and compared with the original estimate.
      RESULTS: A total of 382 patients were used in the validation study. The median
      esophageal cancer-specific survival was 38 months. None of the coefficients re
      estimated in the validation cohort differed significantly from the values of the
      original nomogram. Observed and expected survival curves showed good calibration.
      Discrimination of the original nomogram was preserved in the validation cohort:
      the concordance index hardly decreased from 0.77 in the original cohort to 0.76
      in the validation cohort. CONCLUSIONS: The nomogram model that was originally
      developed in a Dutch institute had good individual discriminatory properties and
      good overall calibration when applied to an independent series of patients. The
      nomogram was updated using the data from both cohorts to provide even more robust
      estimates of survival for individual patients. This tool is clinically helpful to
      supply more reliable prognostic information, to offer tailored follow-up
      schedules and/or novel therapeutic strategies in subgroups of patients with
      higher risk of recurrence.

PMID- 19092346
TI  - Neoadjuvant chemotherapy generates a significant tumor response in resectable
      pancreatic cancer without increasing morbidity: results of a prospective phase II
      trial.
AB  - OBJECTIVE: To evaluate the morbidity of pancreaticoduodenectomy after neoadjuvant
      chemotherapy for resectable pancreatic cancer and to assess its histologic and
      metabolic response. BACKGROUND: Adjuvant chemotherapy improves the outcome of
      pancreatic cancer, but 25% of patients remain unfit after surgery. Neoadjuvant
      chemotherapy can be offered to all patients in a multimodality approach, but its
      efficacy and surgical morbidity are unknown. METHODS: Patients with resectable,
      cytologically proven adenocarcinoma of the pancreatic head received 4 bi-weekly
      cycles of gemcitabine (1000 mg/m(2)) and cisplatin (50 mg/m(2)) in this
      prospective phase II trial. Staging and restaging included chest x-ray, abdominal
      computed tomography (CT), positron emission tomography (PET)/CT, endoscopic
      ultrasound, and laparoscopy. Fluorodeoxyglucose uptake was quantified by the
      standard-uptake value (SUV) on baseline and restaging PET/CT.
      Immunohistochemistry for GLUT-1 and Ki-67 was performed. The histologic response,
      cytopathic effects, and surgical complications were graded by respective scores.
      RESULTS: Twenty-four of 28 patients had resection for histologically confirmed
      adenocarcinoma. The surgical morbidity was low without perioperative death and
      one pancreatic fistula. Histologic response was documented in 54% and cytopathic
      effects in 83% of the patients. A significant SUV decrease occurred during
      chemotherapy (P = 0.031), which correlated with the baseline SUV (P = 0.001), Ki
      67 expression (P = 0.016), and histologic response (P = 0.01). Neither the
      metabolic nor the histologic response was predictive of the median disease-free
      (9.2 months) or overall survival (26.5 months). CONCLUSION: Neoadjuvant
      chemotherapy induced a significant metabolic and histologic response, which was
      best predicted by PET. Most importantly, surgery after neoadjuvant chemotherapy
      for pancreatic cancer was safe.

PMID- 19092347
TI  - Randomized controlled trial of laparoscopic Heller myotomy plus Dor
      fundoplication versus Nissen fundoplication for achalasia: long-term results.
AB  - OBJECTIVES: To compare in a prospective, randomized trial the long-term results
      of laparoscopic Heller myotomy plus Dor fundoplication versus laparoscopic Heller
      myotomy plus floppy-Nissen for achalasia. SUMMARY BACKGROUND DATA: Anterior
      fundoplication is usually performed after Heller myotomy to control GER; however,
      the incidence of postoperative GER ranges between 10% and 30%. Total
      fundoplication may aid in reducing GER rates. METHODS: From December 1993 to
      September 2002, 153 patients with achalasia underwent Heller laparoscopic myotomy
      plus antireflux fundoplication. Of these, 9 were excluded from the study. The
      remaining 144 patients were randomly assigned to 2 treatment groups: Heller
      laparoscopic myotomy plus anterior fundoplication (Dor procedure) or Heller
      laparoscopic myotomy plus total fundoplication (floppy-Nissen procedure). The
      primary end point was incidence of clinical and instrumental GER after a minimum
      of 60 months follow-up. The secondary end point was recurrence of dysphagia.
      Follow-up clinical assessments were performed at 1, 3, 12, and 60 months using a
      modified DeMeester Symptom Scoring System (MDSS). Esophageal manometry and 24
      hour pH monitoring were performed at 3, 12, and 60 months postoperative. RESULTS:
      Of the 144 patients originally included in the study, 138 were available for long
      term analysis: 71 (51%) underwent antireflux fundoplication plus a Dor procedure
      (H + D group) and 67 (49%) antireflux fundoplication plus a Nissen procedure (H +
      N group). No mortality was observed. The mean follow-up period was 125 months. No
      statistically significant differences in clinical (5.6% vs. 0%) or instrumental
      GER (2.8% vs. 0%) were found between the 2 groups; however, a statistically
      significant difference in dysphagia rates was noted (2.8% vs. 15%; P < 0.001).
      CONCLUSIONS: Although both techniques achieved long-term GER control, the
      recurrence rate of dysphagia was significantly higher among the patients who
      underwent Nissen fundoplication. This evidence supports the use of Dor
      fundoplication as the preferred method to re-establish GER control in patients
      undergoing laparoscopic Heller myotomy.

PMID- 19092348
TI  - Adjuvant intra-arterial chemotherapy and radiotherapy versus surgery alone in
      resectable pancreatic and periampullary cancer: a prospective randomized
      controlled trial.
AB  - BACKGROUND: Success of surgical treatment for pancreatic and periampullary cancer
      is often limited due to locoregional recurrence and/or the development of distant
      metastases. OBJECTIVE: The survival benefit of celiac axis infusion (CAI) and
      radiotherapy (RT) versus observation after resection of pancreatic or
      periampullary cancer was investigated. METHODS: In a randomized controlled trial,
      120 consecutive patients with histopathologically proven pancreatic or
      periampullary cancer received either adjuvant treatment consisting of intra
      arterial mitoxantrone, 5-FU, leucovorin, and cisplatinum in combination with 30 x
      1.8 Gy radiotherapy (group A) or no adjuvant treatment (group B). Groups were
      stratified for tumor type (pancreatic vs. periampullary tumors). RESULTS: After
      surgery, 120 patients were randomized (59 patients in the treatment group, 61 in
      the observation group). The median follow-up was 17 months. No significant
      overall survival benefit was seen (median, 19 vs. 18 months resp.). Progressive
      disease was seen in 86 patients: in 37 patients in the CAI/RT group, and in 49
      patients in the observation group (log-rank P < 0.02). Subgroup analysis showed
      significantly less liver metastases after adjuvant treatment in periampullary
      tumors (log-rank P < 0.03) without effect on local recurrence. Nonetheless, there
      was no significant effect on overall survival in these patients (log-rank P =
      0.15). In patients with pancreatic cancer, CAI/RT had no significant effect on
      local recurrence (log-rank P = 0.12) neither on the development of liver
      metastases (log-rank P = 0.76) and consequently, no effect on overall survival.
      CONCLUSION: This adjuvant treatment schedule results in a prolonged time to
      progression. For periampullary tumors, CAI/RT induced a significant reduction in
      the development of liver metastases, with a possible effect on overall survival.
      Especially in these tumors, CAI/RT might prove beneficial in larger groups and
      further research is warranted.

PMID- 19092349
TI  - Methylprednisolone therapy in deceased donors reduces inflammation in the donor
      liver and improves outcome after liver transplantation: a prospective randomized
      controlled trial.
AB  - OBJECTIVE: To investigate potential beneficial effects of donor treatment with
      methylprednisolone on organ function and outcome after liver transplantation.
      SUMMARY BACKGROUND DATA: It is proven experimentally and clinically that the
      brain death of the donor leads to increased levels of inflammatory cytokines and
      is followed by an intensified ischemia/reperfusion injury after organ
      transplantation. In experiments, donor treatment with steroids successfully
      diminished these effects and led to better organ function after transplantation.
      METHODS: To investigate whether methylprednisolone treatment of the deceased
      donor is applicable to attenuate brain death-associated damage in clinical liver
      transplantation we conducted a prospective randomized treatment-versus-control
      study in 100 deceased donors. Donor treatment (n = 50) consisted of 250 mg
      methylprednisolone at the time of consent for organ donation and a subsequent
      infusion of 100 mg/h until recovery of organs. A liver biopsy was taken
      immediately after laparotomy and blood samples were obtained after brain death
      diagnosis and before organ recovery. Cytokines were assessed by real-time reverse
      transcriptase-polymerase chain reaction. Soluble serum cytokines were measured by
      cytometric bead array system. RESULTS: After methylprednisolone treatment,
      steroid plasma levels were significantly higher (P < 0.05), and a significant
      decrease in soluble interleukins, monocyte chemotactic protein-1, interleukin-2,
      interleukin-6, tumor necrosis factor-alpha, and inducible protein-10 was
      observed. Methylprednisolone treatment resulted in a significant downregulation
      of intercellular adhesion molecule-1, tumor necrosis factor-alpha, major
      histocompatibility complex class II, Fas-ligand, inducible protein-10, and CD68
      intragraft mRNA expression. Significantly ameliorated ischemia/reperfusion injury
      in the posttransplant course was accompanied by a decreased incidence of acute
      rejection. CONCLUSIONS: Our present study verifies the protective effect of
      methylprednisolone treatment in deceased donor liver transplantation, suggesting
      it as a potential therapeutical approach.

PMID- 19092350
TI  - Anticatabolic effects of avoiding preoperative fasting by intravenous hypocaloric
      nutrition: a randomized clinical trial.
AB  - OBJECTIVE: We tested the hypothesis that the avoidance of preoperative fasting by
      hypocaloric nutrition attenuates protein catabolism after surgery. SUMMARY
      BACKGROUND DATA: Prolonged fasting before major abdominal procedures has been
      demonstrated to accentuate the catabolic response to surgery. METHODS: Twenty-two
      patients undergoing colorectal cancer surgery were randomly assigned to receive
      glucose and amino acids intravenously starting either 20 hours before the
      operation or with surgical skin incision. Nutrition was administered until the
      second postoperative day, with glucose providing 50% and amino acids 20% of each
      patient's measured resting energy expenditure. Whole body leucine and glucose
      kinetics were assessed by L-[1-(13)C]leucine and [6,6-(2)H(2)]glucose before and
      after surgery. Fractional synthesis rates of muscle protein, albumin, and
      fibrinogen were determined using primed continuous infusions of L
      [(2)H(5)]phenylalanine postoperatively, whereas the expression of mRNA of
      proteolytic genes in muscle (Mafbx/atrogin-1, ubiquitin, Murf 1) was determined
      by quantitative RT-PCR. Circulating concentrations of glucose, lactate, amino
      acids, insulin, glucagon, and cortisol were also measured. This study has been
      registered at ClinicalTrials.gov (Identifier: NCT00614133). RESULTS: Preoperative
      feeding inhibited endogenous protein breakdown (fasting group: 128 +/- 23
      micromol . kg(-1) . h(-1); nutrition group: 96 +/- 22 micromol . kg(-1) . h(-1);
      P = 0.02) and blunted the increase in amino acid oxidation (fasting group: 27 +/-
      5 micromol . kg(-1) . h(-1); nutrition group: 20 +/- 5 micromol . kg(-1) . h(-1);
      P = 0.03), resulting in positive whole-body protein balance after surgery
      (fasting group: -10 +/- 4 micromol . kg(-1) . h(-1); nutrition group: 1 +/- 3
      micromol . kg(-1) . h(-1); P < 0.001). This anabolic response was associated with
      decreased muscle proteolytic gene expression and increased hepatic albumin
      synthesis. Total plasma protein, fibrinogen, and muscle protein synthesis were
      not affected. CONCLUSIONS: Hypocaloric nutrition decreases protein catabolism,
      with a contribution from the ubiquitin pathway in muscle, and stimulates albumin
      synthesis after colorectal surgery if initiated 1 day before the operation.

PMID- 19092351
TI  - Randomized controlled trial on single dose steroid before thyroidectomy for
      benign disease to improve postoperative nausea, pain, and vocal function.
AB  - OBJECTIVE: To evaluate the effects of a single preoperative dose of steroid on
      thyroidectomy outcomes. BACKGROUND: Nausea, pain, and voice alteration frequently
      occur after thyroidectomy. Because steroids effectively reduce nausea and
      inflammation, a preoperative administration of steroids could improve these
      thyroidectomy outcomes. METHODS: Seventy-two patients (men = 20, women = 52)
      undergoing thyroidectomy for benign disease were included in this randomized,
      controlled, 2 armed (group D: 8 mg dexamethasone, n = 37; group C: 0.9% NaCl, n =
      35), double-blinded study (clinical trial number NCT00619086). Anesthesia,
      surgical procedures, antiemetics, and analgesic treatments were standardized.
      Nausea (0-3), pain (visual analog scale), antiemetic and analgesic requirements,
      and digital voice recording were documented before and 4, 8, 16, 24, 36, and 48
      hours after surgery. Patients were followed-up 30 days after hospital discharge.
      RESULTS: Baseline characteristics were similar among the 2 treatment groups.
      Nausea was pronounced in the first 16 hours postoperatively (scores were <0.3 and
      0.8-1.0 for group D and C, respectively (P = 0.005)), and was significantly lower
      in group D compared with group C during the observation period (P = 0.001). Pain
      diminished within 48 hours after surgery (visual analog scale 20 and 35 in group
      D and C, respectively (P = 0.009)). Antiemetic and analgesic requirements were
      also significantly diminished. Changes in voice mean frequency were less
      prominent in the dexamethasone group compared with the placebo group (P = 0.015).
      No steroid-related complications occurred. CONCLUSION: A preoperative single dose
      of steroid significantly reduced nausea, vomiting, and pain, and improved
      postoperative voice function within the first 48 hours (most pronounced within 16
      hours) after thyroid resection; this strategy should be routinely applied in
      thyroidectomies.

PMID- 19092352
TI  - The ratio of metastatic to examined lymph nodes is a powerful independent
      prognostic factor in rectal cancer.
AB  - OBJECTIVE: The aim of the study was to evaluate the prognostic value of the ratio
      of metastatic to examined lymph nodes (LNR) in patients with rectal cancer.
      SUMMARY BACKGROUND DATA: Lymph nodes ratio (LNR) has been shown to have
      prognostic value in patients with colon cancer. The impact of LNR on disease-free
      and overall survival in patients with rectal cancer is unknown. PATIENTS AND
      METHODS: From 1998 to 2004, 307 patients underwent rectal resection for
      adenocarcinoma. The relationships between overall and disease-free survival at 3
      years and 15 variables, including the presence or absence of metastatic lymph
      nodes, the total number of lymph nodes examined, and LNR, were analyzed by
      multivariate analysis. Patients were then assigned to 4 groups based on LNR: LNR
      = 0 (N0 patients), LNR = 0.01 to 0.07, LNR >0.07 to 0.2, LNR >0.2. RESULTS: The
      mean number of lymph nodes examined was 22 +/- 12. In the multivariate analysis,
      LNR was a significant prognostic factor for both disease-free (P = 0.006) and
      overall survival (P = 0.0003), whereas the presence or absence of metastatic
      lymph nodes was not. LNR remained a significant prognostic factor in the 59
      patients in whom fewer than 12 lymph nodes were examined (P = 0.0058). According
      to LNR values, disease-free and overall survival decreased significantly with
      increasing LNR (P < 0.001). CONCLUSIONS: LNR is the most significant prognostic
      factor for both overall and disease-free survival in patients with rectal cancer,
      even in patients with fewer than 12 lymph nodes examined.

PMID- 19092353
TI  - Peroral transgastric/transduodenal necrosectomy: success in the treatment of
      infected pancreatic necrosis.
AB  - OBJECTIVE: To assess the results and complications of an endoscopic
      transgastric/transduodenal approach as a possible alternative to conventional
      surgery. SUMMARY BACKGROUND DATA: Infected organized pancreatic necrosis carries
      a high mortality despite antibiotic therapy and numerous conventional and
      laparoscopic surgical techniques of debridement. The advent of natural orifice
      transluminal endoscopic surgery (NOTES) provides a possible alternative approach.
      METHODS: Between 2004 and 2007, patients with infected organized pancreatic
      necrosis were referred for endoscopic necrosectomy as their initial treatment of
      choice. Accessibility was confirmed by CT and endoscopic ultrasound. Access to
      the cavities was transgastric or transduodenal, after passing the endoscope
      inside the retroperitoneal cavity all necrotic and purulent material was
      evacuated under direct endoscopic vision. RESULTS: Thirteen patients (12 men,
      mean age: 55 years, range: 38-66 years) underwent endoscopic necrosectomy. Two
      patients had complementary percutaneous drainage for endoscopically inaccessible
      cavities. Resolution infection was the rule in all cases. Infection recurred in 4
      patients and a necrotic cavity persisted in 1 patient; all were managed by
      further endoscopic necrosectomies (total = 23 necrosectomy sessions; mean, 1.8
      per patient; range, 1-3). Mean duration of each session was 3.5 hours (range, 2.5
      4 hours). Endoscopic treatment was eventually successful in all patients with
      gradual diminution of the necrotic cavities on CT images. Average duration of
      follow-up was 19.5 months (range, 2-56 months) with no recurrence of the
      infectious process and no surgery was required for any patient. Complications
      included bleeding (n = 3) and transient aggravation of sepsis (n = 3). No
      mortality occurred. CONCLUSIONS: This technique is highly effective and safe in
      the treatment of infected organized pancreatic necrosis. Results are achievable
      and sustainable with a limited number of sessions.

PMID- 19092354
TI  - Minimally invasive esophagectomy: lessons learned from 104 operations.
AB  - OBJECTIVES: To review the outcomes of 104 consecutive minimally invasive
      esophagectomy (MIE) procedures for the treatment of benign and malignant
      esophageal disease. SUMMARY BACKGROUND DATA: Although minimally invasive surgical
      approaches to esophagectomy have been reported since 1992, MIE is still
      considered investigational at most institutions. METHODS: This prospective study
      evaluates 104 MIE procedures performed between August 1998 and September 2007.
      Main outcome measures include operative techniques, operative times, blood loss,
      length of stay, conversion rates, morbidities, and mortalities. RESULTS:
      Indications for surgery were esophageal cancer (n = 80), Barrett esophagus with
      high-grade dysplasia (n = 6), recalcitrant stricture (n = 8), gastrointestinal
      stromal tumor (n = 3), and gastric cardia cancer (n = 7). Surgical approaches
      included thoracoscopic/laparoscopic esophagectomy with a cervical anastomosis (n
      = 47), minimally invasive Ivor Lewis esophagectomy (n = 51), laparoscopic hand
      assisted blunt transhiatal esophagectomy (n = 5), and laparoscopic proximal
      gastrectomy (n = 1). There were 77 males. The mean age was 65 years. Three
      patients (2.9%) required conversion to a laparotomy. The median ICU and hospital
      stays were 2 and 8 days, respectively. Major complications occurred in 12.5% of
      patients and minor complications in 15.4% of patients. The incidence of leak was
      9.6% and of anastomotic stricture was 26%. The 30-day mortality was 1.9% with an
      in-hospital mortality of 2.9%. The mean number of lymph nodes retrieved was 13.8.
      CONCLUSIONS: Minimally invasive esophagectomy is feasible with a low conversion
      rate, acceptable morbidity, and low mortality. Our preferred operative approach
      is the laparoscopic?thoracoscopic Ivor Lewis resection, which provides a tension
      free intrathoracic anastomosis.

PMID- 19092355
TI  - Laparoscopic resection for diverticular disease: follow-up of 500 consecutive
      patients.
AB  - OBJECTIVE: To examine morbidity, mortality, conversion rates, and disease
      recurrence after laparoscopic resection of complicated and uncomplicated
      diverticular disease in a single center. SUMMARY BACKGROUND DATA: In contrast to
      colorectal cancer, there are few large studies of laparoscopic or open resection
      for diverticular disease. METHODS: This study represents a retrospective analysis
      of a prospectively collected database of all laparoscopic resections for
      uncomplicated and complicated diverticulitis from a single center. RESULTS: Five
      hundred patients (305 female) were identified (median age 58; range, 26-89).
      Recurrent diverticulitis was the most common indication for surgery (77%),
      followed by perforation (10%) and fistulation (9%). Median operating time was 120
      minutes (range, 45-285) and median length of hospital stay was 4 (2-33) days. The
      splenic flexure was routinely mobilized. There was 1 (0.2%) 30-day and in
      hospital death and 55 (11%) patients had major morbidity after the procedure.
      Conversion to an open operation was performed in 14 (2.8%) cases. Dense adhesions
      were the most common cause for conversion (6 patients). Among patients with
      complicated diverticulitis, the conversion rate was 5.3%, whereas for those with
      uncomplicated disease, it was 2.1% (P = ns). Operating time and length of
      hospital stay do not differ significantly between patients with complicated and
      uncomplicated diverticulitis. The conversion rate has come down from 8% for the
      first 100 cases to 1.5% for the last 400 cases (P = 0.002). To our knowledge,
      there have been no cases of recurrent diverticulitis. CONCLUSIONS: Laparoscopic
      resection even in complicated cases of diverticulitis is safe and effective. It
      can be achieved with short operating times and length of stay in conjunction with
      very low rates of morbidity and mortality. Adherence to surgical principles
      including routine mobilization of the splenic flexure and anastomosis onto the
      rectum may explain the absence of disease recurrence in our experience.

PMID- 19092356
TI  - Anatomy of the superior mesenteric vein with special reference to the surgical
      management of first-order branch involvement at pancreaticoduodenectomy.
AB  - OBJECTIVE: To describe our approach to resection of pancreatic head cancers,
      which involve 1 or both of the first-order branches of the superior mesenteric
      vein (SMV). SUMMARY BACKGROUND DATA: In contrast to tumors which involve the
      proximal SMV, cancers in the inferior aspect of the pancreatic head or root of
      mesentery (mid gut carcinoid) may involve one of the 2 primary branches of the
      SMV (the ileal and jejunal branches), with or without involvement of the main
      trunk of the SMV. Such cases are associated with significant technical
      challenges. METHODS: Our surgical approach is described and illustrated. RESULTS:
      Isolated involvement of the jejunal branch of the SMV may be managed by division
      of this branch without reconstruction as long as the ileal branch is intact and
      of good caliber. Tumors which involve the ileal branch of the SMV, in the rare
      setting in which the jejunal branch is preserved, may also be managed by ligation
      and resection without reconstruction. Involvement of one of these first-order
      branches in association with more proximal involvement of the main trunk of the
      SMV may be successfully managed by ligation of one first-order branch and
      concurrent segmental resection and reconstruction of the other branch, and the
      main SMV trunk, with or without an interposition graft. CONCLUSION: Segmental
      resection of one of the 2 first-order branches of the SMV may be performed
      without venous reconstruction if mesenteric venous flow is preserved through the
      remaining first-order branch. Detailed knowledge of the vascular anatomy of the
      root of the mesentery is necessary for the performance of complex surgical
      procedures involving the pancreatic head and root of mesentery.

PMID- 19092358
TI  - APER rate has multiple limitations as an indicator of quality in rectal cancer
      surgery.

PMID- 19092359
TI  - CONSORT and QUOROM statements revisited: standards of reporting of randomized
      controlled trials in general surgery.

PMID- 19092361
TI  - Early oral feeding after major digestive surgery.

PMID- 19092363
TI  - Polypoid lesions of the gallbladder: does size matter?

PMID- 19092364
TI  - Cytokines and myocardial regeneration: a novel treatment option for acute
      myocardial infarction.
AB  - The regenerative capacity of the myocardium and its blood vessels has now been
      well demonstrated. The cytokines granulocyte colony-stimulating factor,
      erythropoietin, and stem cell factor may play a role in helping to stimulate cell
      regeneration under normal physiologic conditions and in patients with myocardial
      injury. After an ischemic insult, cytokines are released into the peripheral
      circulation and signal for the mobilization of stem cells. In experimental
      cardiac injury models, the addition of cytokines has been shown to improve
      myocardial function with and without the concurrent use of stem cell therapy.
      Preliminary studies in humans using cytokine therapy alone for treating
      myocardial infarction have been disappointing. Future studies in patients with
      myocardial injury need to examine the use of various combinations of cytokines,
      with and without the addition of intravascular stem cell infusions or direct stem
      cell injections.

PMID- 19092365
TI  - Vasopressin and vasopressin receptor antagonists in heart failure.
AB  - Antidiuretic hormone, also known as arginine vasopressin, is a hormone with a
      multitude of physiologic activities including the control of urinary free water
      excretion. Antidiuretic hormone also plays a role in vasoconstriction and has 3
      receptors that have been identified. Vasopressin analogs and antagonists have
      been extensively studied in animal models as well as in humans. Because heart
      failure is associated with a state of water retention, several vasopressin
      antagonists have been evaluated for their potential aquaretic effect. Diuretics
      remain the mainstay of treatment in acute and chronic volume overload but are not
      shown to improve survival. In fact, they are associated with numerous side
      effects including hypotension, electrolyte abnormalities, worsening renal
      function, and activation of renin-angiotensin-aldosternone system. Tolvaptan,
      conivaptan, and lixivaptan are some of the vasopressin antagonists that have been
      studied in heart failure. The results were initially encouraging with alleviation
      of symptoms and effective aquaresis without worsening of hyponatremia or renal
      function, but yet failed to show any effect on mortality in heart failure. With
      an increasing number of more selective orally active vasopressin antagonists,
      further studies are underway to establish the role of "Vaptans" in the treatment
      of heart failure and other disease states with volume overload and hyponatremia.

PMID- 19092366
TI  - Superior vena cava syndrome: a contemporary review of a historic disease.
AB  - Superior vena cava (SVC) syndrome is a historic entity that is reemerging as an
      important, albeit still uncommon, contemporary vascular disease condition. The
      causes of SVC syndrome have evolved dramatically over the last century: whereas
      the majority of originally described cases were due to infection, contemporary
      presentations are now predominantly associated with the presence of an
      intravascular device and/or mediastinal malignancy. Multiple underlying
      pathologic mechanisms often coexist to confer risk for SVC syndrome. Although the
      diagnosis is still best made at the bedside, advanced imaging modalities may be
      used to clarify etiology, grade severity, and facilitate intervention. Treatment
      of SVC syndrome often requires a combination of noninvasive and invasive
      therapies. With regard to invasive strategies, endovascular approaches to
      revascularization are now considered first-line given their relative safety and
      efficacy. Fortunately, both endovascular and open surgical interventions can
      offer definitive therapy in a majority of cases.

PMID- 19092367
TI  - Diagnostic approach and role of MRI in the assessment of acute myocarditis.
AB  - The diagnosis of acute myocarditis can be challenging, primarily because of the
      clinical diversity at presentation, the nonspecificity of traditional noninvasive
      tests, as well as the poor diagnostic yield and potential complications inherent
      with endomyocardial biopsy. Contrast-enhanced and nonenhanced cardiac magnetic
      resonance imaging (MRI) is emerging as an imaging modality of choice to diagnose
      and monitor the progression of myocarditis. MRI is nonionizing, non-nephrotoxic,
      and in comparison to coronary angiography, allows the clinician to rapidly
      eliminate irreversible ischemic injury (acute coronary syndrome) from the
      differential diagnosis. This timely review discusses the advantages and
      limitations of cardiac MRI over alternative diagnostic modalities and offers a
      practical approach to the contemporary diagnosis and assessment of acute
      myocarditis.

PMID- 19092368
TI  - Fabry disease: cardiac manifestations and therapeutic options.
AB  - Fabry disease is a rare inherited lysosomal storage disorder caused by the
      partial or complete deficiency of the lysosomal enzyme alpha galactosidase A
      (alpha-Gal A), resulting in excess cellular glycosphingolipid deposition.
      Accumulation of the neutral glycosphingolipid globotriaosyl-ceramide predominates
      and involves small blood vessels, nerves, dorsal root ganglia, renal glomerular,
      and tubular epithelial cells and cardiomyocytes. Disease transmission is X
      linked, therefore it predominantly affects males and females as asymptomatic
      carriers. However, females may also develop symptomatic disease of varying
      severity. Glycosphingolipid deposition in various tissues leads to episodic pain
      crises and acroparesthesias, gastrointestinal disturbances, angiokeratomas,
      corneal, and lenticular opacities, and eventually in the third to fifth decades
      of life, the kidney, heart and central nervous system are involved. Cardiac
      involvement is usually part of the multisystem disorder and presents in the
      fourth decade with other organ manifestations; however, a variant of Fabry
      disease with predominant cardiac manifestations has also been recognized.
      Patients may present with angina pectoris, dyspnea, palpitations, or syncope, and
      these symptoms are due to vascular, endothelial, myocardial (with increase in
      left ventricular mass), and conduction system involvement. Advanced cardiac
      disease may require a permanent pacemaker and cardiac transplant. Substrate
      inhibition with enzyme replacement therapy and gene therapy instituted early in
      the disease course might slow progression of the cardiac manifestations.

PMID- 19092369
TI  - An integrated approach to the diagnosis and treatment of anxiety within the
      practice of cardiology.
AB  - Coronary heart disease (CHD) is the leading cause of death and disability in the
      United States and in highly industrialized countries. Many modifiable
      psychosocial risk factors have been identified and can affect the course of
      cardiac illness. These include the negative emotional states of depression,
      anxiety, stress, anger/hostility, and social isolation. Anxiety has been found to
      increase the risk of developing CHD in healthy subjects and can lead to worsening
      of existing CHD. There is much overlap and confusion throughout the research
      literature between what authors define as anxiety, stress, Type A behavioral
      pattern, and anger/hostility.There is a need for better screening within the
      practice of cardiology for these psychosocial risk factors to ensure better
      integration of mental health services. Established screening tools such as the
      Beck Anxiety Inventory, Patient Health Questionnaire-9, Zung Self-Rating Anxiety
      Scale, and the Hamilton Anxiety Scale are described and compared with the newer
      Screening Tool for Psychologic Distress as part of the initial work-up of every
      cardiac patient. Recommendations are made using the author's Anxiety Treatment
      Algorithm regarding when to refer to a mental health professional along with how
      to reduce stigma and provide more integrated care. The diagnosis and treatment of
      anxiety disorders is reviewed, with attention to selective serotonin reuptake
      inhibitors, benzodiazepines, cognitive-behavioral therapy, stress reduction, and
      behavioral medicine group programs. These group programs are recommended because
      they help to overcome social isolation and counsel patients on how to adapt to a
      healthy lifestyle. Better clinical outcome research is needed that specifically
      addresses the question of whether the treatment of anxiety and anxiety disorders
      can affect the course of cardiac illness.

PMID- 19092370
TI  - Antiretroviral and statin drug-drug interactions.
AB  - Patients living with the human immunodeficiency virus (HIV) are at risk for
      dyslipidemia as a result of the disease itself and from certain classes of
      antiretroviral therapy. The protease inhibitors and non-nucleoside reverse
      transcription inhibitors have been associated with elevated triglycerides, total,
      and low-density lipoprotein cholesterol with decreased high-density lipoprotein.
      These classes of medications affect the cytochrome P450 (CYP) enzyme resulting in
      both induction and inhibition of numerous CYP enzymes. The statins are
      extensively metabolized by the CYP system and therefore drug-drug interactions
      between the statins and antiretroviral therapy must be considered when treating
      HIV or antiretroviral drug-induced dyslipidemia.

PMID- 19092371
TI  - Value of precise localization of recurrent multiple myeloma with F-18 FDG PET/CT.
AB  - A 37-year-old man with multiple myeloma in remission underwent routine
      fluorodeoxyglucose-positron emission tomography/computed tomography (FDG-PET/CT)
      study for disease restaging. Both FDG-PET and CT images showed focal
      abnormalities in the region of the T6 vertebra, but the fused images that are
      routinely provided with PET/CT could precisely localize the FDG active lesion to
      a soft tissue focus in the epidural space, away from a lytic nonactive vertebral
      body lesion despite their close proximity. The PET/CT scan identified a few other
      metabolically active osseous lesions out of many lytic bony changes throughout
      the skeleton. Accordingly, the patient received the correct management for an
      impending spinal cord compression at the appropriate time, in addition to
      systemic therapy for disease relapse.

PMID- 19092372
TI  - The role of radioactive iodine therapy in young patients with papillary thyroid
      cancer.
AB  - PURPOSE: The aim of this study was to investigate the outcome of postoperative
      radioactive iodine (I-131) therapy in young patients with papillary thyroid
      carcinoma (PTC). MATERIALS AND METHODS: This retrospective study reviewed the
      medical records of primary PTC patients, 18 years old or younger, who were
      treated at Chang Gung Medical Center in Taiwan from January 1977 to December
      2006. Forty-eight patients who had undergone postoperative I-131 therapy with a
      minimum dose of 1.1 GBq (30 mCi) were enrolled in this retrospective study. At
      the end of follow-up, patients were classified as "local disease" or "distant
      metastases" according to I-131 scan results. RESULTS: The I-131 whole-body scan
      results revealed "local disease" in 34 patients, and "distant metastases" in 14
      patients. Patients with distant metastases received significantly larger doses of
      I-131 than those with local disease (P = 0.0086). One-month postoperative serum
      thyroglobulin differed markedly between patients with local disease and those
      with distant metastases (P = 0.001). After a mean follow-up period of 11.2 +/-
      5.7 years, overall survival in the 48 patients was 97.9%. CONCLUSIONS: I-131
      therapy is effective for young PTC patients, and should be given to all young PTC
      patients postoperatively in addition to thyroid hormone administration,
      particularly those with distant metastases.

PMID- 19092373
TI  - C-11 choline versus F-18 fluorodeoxyglucose for imaging meningiomas: an initial
      experience.
AB  - PURPOSE: Positron emission tomography/computed tomography (PET/CT) with C-11
      choline has been used for staging, restaging, and follow-up of various tumors,
      whereas its role for imaging meningiomas has only been preliminarily explored.
      The aim of this study was to compare C-11 choline and F-18 fluorodeoxyglucose (F
      18 FDG) uptake in meningiomas and relate these findings to the histopathological
      analysis. METHODS: Two sequential three-dimensional PET/CT scans with 370 MBq (10
      mCi) of C-11 choline and 370 MBq (10 mCi) of F-18 FDG were performed 2 hours
      apart in 7 patients with histologically confirmed meningiomas. Five patients had
      WHO grade I and 2 had WHO grade II meningioma. For each scan, two-dimensional
      regions of interest were drawn on tumor boundaries and on the contralateral side
      on CT images and copied to the corresponding PET images. SUVmax and tumor-to
      background ratio were calculated. RESULTS: Relative to the contralateral side, C
      11 choline uptake was increased in all meningiomas, whereas F-18 FDG uptake was
      decreased in 6 patients and increased in 1 of the 2 patients with grade II
      meningiomas. In the whole group, SUVmax of C-11 choline and F-18 FDG were 3.6 +/-
      1.3 and 5.7 +/- 1.3, respectively. The tumor-to-background ratio for C-11 choline
      was much higher than that for F-18 FDG (5.3 +/- 0.8 vs. 0.9 +/- 0.2,
      respectively) (P < 0.001). The uptake of C-11 choline was higher in patients with
      grade II than in grade I meningiomas. CONCLUSIONS: These preliminary results
      suggest that C-11 choline may better image meningiomas in comparison with F-18
      FDG. Clinical applications of C-11 choline PET/CT for grading and follow-up of
      meningiomas need to be assessed in further studies.

PMID- 19092374
TI  - Clinical implications of diffuse hepatic uptake observed in postablative and post
      therapeutic I-131 scans.
AB  - Diffuse hepatic uptake of I-131 either on diagnostic or post-therapeutic scans is
      a usual finding in patients with differentiated thyroid carcinoma. The aim of
      this study was to evaluate the frequency and clinical significance of diffuse
      hepatic uptake of radioiodine on post-therapeutic (PT) and postablative (PA)
      whole-body scans.A total of 720 PA and 172 PT I-131 scans in a total of 732
      patients with differentiated thyroid carcinoma were retrospectively reviewed.
      Residual thyroid tissue and diffuse liver uptake of I-131 were classified from 0
      to 4. The correlation between the liver and thyroid remnant uptake score, dose of
      radioiodine, serum thyroglobuline (Tg), liver function test levels (ALT, AST),
      liver ultrasonography, presence of metastatic foci, and recurrent disease were
      examined.Diffuse hepatic uptake was observed in 701 of 722 (94.2%) PA and 162 of
      172 (97%) PT whole body I-131 scans. Hepatic radioiodine uptake was positively
      correlated with the dose of administered I-131 and increased levels of serum AST
      and ALT. Liver uptake scores of patients with hepatosteatosis were significantly
      higher than all study groups. However, no evidence of a relationship between
      diffuse visualization of liver and serum thyroglobulin levels, uptake score of
      thyroid remnants, presence of local or distant metastatic foci on I-131 scan, and
      recurrence rate could be demonstrated.The lack of correlation between hepatic
      radioactive iodine (RAI) uptake and Tg levels, functioning metastatic tissue or
      thyroid remnants suggests that this finding may be related to factors other than
      thyroid tissue. The positive correlation between administered RAI dose, hepatic
      enzymes and hepatosteatosis support the conclusion that diffuse hepatic RAI
      uptake may be related to different mechanisms as well.

PMID- 19092375
TI  - FDG-PET evaluation of chondromyxoid fibroma of left ilium.

PMID- 19092376
TI  - Extraosseous myxoid chondrosarcoma with pulmonary and nodal metastases on FDG PET
      CT.

PMID- 19092377
TI  - Bone scintigraphy pattern of joint chronic graft-versus-host disease after
      allogeneic bone marrow transplantation.

PMID- 19092378
TI  - Thoracic scintigraphy in aluminosis: lymph node uptake on bone scan.

PMID- 19092379
TI  - Ga-68 DOTATOC PET/CT changed the therapeutic course of a patient with the sudden
      onset of vision problems.

PMID- 19092380
TI  - Tc-99m DTPA cisternography shows disappearance of cerebrospinal fluid leakage
      after standing a short time.

PMID- 19092381
TI  - Graves disease with midline ectopic and bifid pyramidal lobes on pertechnetate
      thyroid scintigraphy.

PMID- 19092382
TI  - Detection of achalasia on thyroid scintigraphy and MRI.

PMID- 19092383
TI  - Visualization of mesenteric arterial collaterals after occlusion of abdominal
      aorta detected on Tc-99m-labeled red blood cell imaging.

PMID- 19092384
TI  - Abnormal myocardial perfusion imaging after percutaneous coronary intervention
      without obstructing lesion.

PMID- 19092385
TI  - Detection of metastatic involvement of the pericardium on F-18 FDG-PET/CT
      imaging.

PMID- 19092386
TI  - Multiple distal pulmonary arterial thromboses revealed by lung scintigraphy in a
      patient with homocystinuria and normal multidetector CT pulmonary angiography.

PMID- 19092387
TI  - F-18 FDG PET/CT in primary gastric small cell carcinoma.

PMID- 19092388
TI  - Radionuclide imaging of jejunoileal duplication cyst in a child.

PMID- 19092389
TI  - Delayed imaging of Meckel's diverticulum: observation of a quadrantal shift.

PMID- 19092390
TI  - Serendipitous detection of urothelial carcinoma with F-18 FDG PET/CT: usefulness
      of low intensity PET window setting in areas of high physiologic FDG
      distribution.

PMID- 19092391
TI  - Postlithotripsy ureteroileal communication identified on Tc-99m ethylene
      dicysteine renal scintigraphy.

PMID- 19092392
TI  - Unusual urethral F18-FDG accumulation on PET/CT.

PMID- 19092393
TI  - Current readings in nuclear medicine.

PMID- 19092394
TI  - Introducing a new ratio useful in the estimation of preoperative corneal power in
      patients with myopic LASIK based on postoperative corneal data.
AB  - AIM: The aim of this study was to establish a new constant ratio for the
      calculation of preoperative total corneal power using postoperative corneal data
      alone in patients after laser in situ keratomileusis (LASIK). METHODS:
      Preoperative anterior and posterior corneal radii from 192 pre-LASIK eyes were
      analyzed to derive a constant ratio in the first part of the study. In the second
      part of the study, with a set of post-LASIK patients (98 eyes), this ratio was
      used to estimate preoperative total corneal power. This estimated total corneal
      power was compared with the true value obtained from direct preoperative
      measurement. RESULTS: The ratio (R(roc)) between the preoperative anterior
      central 10-mm corneal curvature and the posterior peripheral 7- to 10-mm corneal
      curvature was 1.166 +/- 0.049. Estimated mean preoperative total corneal power
      was 43.42 +/- 2.21 D, whereas the true preoperative mean keratometric value
      (SimK) was 43.40 +/- 2.64 D. The mean difference was 0.02 +/- 2.65 D (P = 0.942).
      CONCLUSIONS: The pre-LASIK corneal power can be estimated using post-LASIK data
      together with R(roc). This will be useful in post-LASIK patients requiring
      cataract surgery but without the availability of pre-LASIK corneal data for the
      estimation of the preoperative keratometric power when the double-K technique was
      used to calculate the intraocular lens power.

PMID- 19092395
TI  - Ocular findings in children with chronic renal failure.
AB  - PURPOSE: The purpose of this study was to describe the ocular findings in
      children with chronic renal failure (CRF). MATERIALS AND METHODS: Nineteen
      children with CRF and 19 age- and sex-matched controls were evaluated. Schirmer
      and tear film break-up time (TBUT) tests were performed in addition to complete
      ophthalmologic examination. The presence of dry eye symptoms was noted. Relation
      between TBUT and Schirmer test results and CRF-related variables such as duration
      of CRF; dialysis status; and serum calcium, phosphorus, urea, and creatinine
      levels was evaluated. Student t test and rank correlation test were used for
      statistical analysis. RESULTS: Dry eye symptoms were detected in 15.8% of
      children with CRF, against none of the controls (chi(2) = 3.25, P = 0.23). TBUT
      and Schirmer test results were significantly lower in the study group than in the
      controls (t = 27.8, P = 0.032 and t = 36.5, P = 0.025, respectively). Within the
      study group, a negative correlation was found between TBUT and Schirmer test
      results and the duration of CRF (R = 0.769, Z = 2.234, P < or = 0.022 and R =
      0.832, Z = 2.351, P < or = 0.019, respectively). No relation was detected between
      the TBUT and Schirmer test results and the dialysis status and serum calcium,
      phosphorus, urea, and creatinine levels in the study group. CONCLUSIONS: The
      basal tear secretion and tear film stability are lower, and the dry eye symptoms
      are more common among the children with CRF. The duration of CRF seems to be
      related with the disturbances in tear secretion and tear film stability.

PMID- 19092396
TI  - Temporal and seasonal trends in Acanthamoeba keratitis.
AB  - PURPOSE: The purpose of this study was to assess the incidence and risk factors
      of Acanthamoeba keratitis (AK) over an 8-year period in a Canadian tertiary care
      setting. METHODS: We retrospectively reviewed the medical records of 41 patients
      (42 eyes), who were diagnosed as having AK between January 1999 and December 2006
      in the cornea clinic at the Toronto Western Hospital. The incidence and risk
      factors of AK were evaluated. RESULTS: The number of cases per year increased
      from between 0 and 4 in the first 5 years to 9, 14, and 8 in the last 3 years.
      The annual increasing trend was statistically significant (P = 0.04). The month
      of onset of disease symptoms showed a trend toward onset in summer and fall and
      was statistically significant for the difference between January and August (P =
      0.0094). The season of onset of disease symptoms showed a trend toward summer
      onset, and the difference between winter and summer was statistically significant
      (P = 0.02). 92.9% of cases occurred in contact lens wearers, particularly in soft
      contact lens wearers (82.1%). CONCLUSIONS: The incidence of AK in Canada may be
      increasing since 2004. There is a seasonal trend toward disease onset in the
      warmer months.

PMID- 19092397
TI  - Role of confocal microscopy in deep fungal keratitis.
AB  - PURPOSE: The purpose of this study was to assess the role of in vivo confocal
      microscopy in cases of fungal keratitis presenting with a deep stromal
      infiltrate. DESIGN: Retrospective, noncomparative case series. METHODS: We
      reviewed the medical, microbiologic, and histopathologic data of 6 patients,
      whose clinical presentation was characterized by deep stromal or multifocal
      endothelial lesions. These patients were subjected to in vivo confocal microscopy
      on the day of presentation. All the patients underwent therapeutic penetrating
      keratoplasty. The excised corneal buttons were bisected and subjected to
      microbiologic and histopathologic examinations. RESULTS: Microbiologic and/or
      histopathologic examination proved that the keratitis in all the 6 patients was
      caused by filamentous fungi. Five corneal buttons were positive for the fungus on
      histopathologic examination. Four specimens grew out fungus on microbiologic
      examination. In 5 (83%) cases, confocal microscopy revealed double-walled,
      septate, linear branching structures resembling fungal filaments. CONCLUSIONS: In
      vivo confocal microscopy can be a useful diagnostic tool in patients presenting
      with deep stromal lesions.

PMID- 19092398
TI  - Penetrating keratoplasty for keratoconus with or without vernal
      keratoconjunctivitis.
AB  - PURPOSE: The purpose of this study was to evaluate graft survival, postoperative
      complications, and visual outcome after penetrating keratoplasty (PKP) for
      keratoconus (KC) in eyes with or without a history of vernal keratoconjunctivitis
      (VKC). METHODS: A retrospective review was conducted on all cases of PKP
      performed at King Khaled Eye Specialist Hospital between January 1, 1997, and
      December 31, 2001, for KC. RESULTS: Four hundred sixty-four eyes were included in
      the study, including 80 (17.2%) eyes with VKC and 384 (82.8%) without VKC. Five
      year graft survival was 97.3% and 95.5% in eyes with or without VKC,
      respectively. There were no statistically significant differences in Kaplan-Meier
      graft survival between the 2 groups at any time interval. There were no
      statistically significant differences in the percentage of eyes experiencing
      postoperative complications in eyes with or without VKC (27.5% vs 31.8%,
      respectively; P = 0.50). However, late-onset persistent epithelial defects were
      significantly more likely to occur in eyes with VKC (6.3% vs 1.8%; P = 0.04).
      There were no significant differences in the prevalence of endothelial rejection,
      bacterial keratitis, glaucoma, wound dehiscence, early-onset persistent
      epithelial defects, or secondary cataract. The median final best-corrected visual
      acuity was 20/30 in both groups. The percentage of eyes with a final best
      corrected visual acuity of 20/40 or better was 76.2% in eyes with VKC and 71.9%
      in eyes without VKC (P = 0.49). CONCLUSIONS: Graft survival, postoperative
      complications, and visual outcome are comparable after PKP for KC in eyes with or
      without VKC.

PMID- 19092399
TI  - Refractive change after descemet stripping automated endothelial keratoplasty
      surgery and its correlation with graft thickness and diameter.
AB  - PURPOSE: The purpose of this study was to evaluate the refractive change after
      Descemet stripping automated endothelial keratoplasty (DSAEK) surgery and its
      correlation with graft thickness and diameter. METHODS: We retrospectively
      analyzed the refractive outcomes of 45 cases of DSAEK surgery that were performed
      at Duke University Eye Center between August 2005 and December 2006. We divided
      our study groups into DSAEK triple cases and pseudophakic DSAEK cases. We
      measured manifest refraction preoperatively and postoperatively in each group and
      compared the difference between the preoperative and the postoperative spherical
      equivalent. We evaluated the correlation of the refractive change with graft
      thickness and diameter. RESULTS: Forty-five DSAEK cases in 44 patients (27 women
      and 17 men) were evaluated and analyzed. Mean age of the patients at surgery was
      67.6 years (15-81 years, SD 10.7 years). Forty cases were treated for Fuchs
      endothelial dystrophy and 5 for pseudophakic bullous keratopathy/bullous
      keratopathy. Seventeen cases were DSAEK triple cases and 28 pseudophakic DSAEK
      cases. In the DSAEK triple group, the mean change in refraction at an average of
      4 months postoperatively was +1.15 D (range -0.02 to 2.87, SD 1.15). In the
      pseudophakic DSAEK group, the mean change in refraction at an average of 5 months
      postoperatively was +0.71 D (range -1.75 to 3.0, SD 1.11). The overall refractive
      change was +0.88 D (range -1.75 to 3.0, SD 1.02). Correlation of refractive
      change with graft diameter was modest (r = 0.29, P = 0.05), and a small
      correlation was found with respect to graft thickness (r = -0.16, P = 0.31).
      CONCLUSIONS: Our study of DSAEK grafts demonstrated a hyperopic refractive shift
      after DSAEK surgery. This observation should be taken into consideration when
      deciding on the appropriate intraocular lens power in DSAEK triple surgery and
      may also aid in anticipating refractive outcomes after pseudophakic DSAEK
      surgery. Further studies to follow these refractive changes over a longer follow
      up period and to investigate the mechanism of this refractive change after DSAEK
      surgery are warranted.

PMID- 19092400
TI  - Endothelial keratoplasty: the influence of insertion techniques and incision size
      on donor endothelial survival.
AB  - PURPOSE: To determine the acute endothelial cell damage from trephination and
      tissue insertion in endothelial keratoplasty (EK) surgery. The influence of
      insertion technique (forceps insertion vs "pull-through" insertion) of donor
      tissue and incision size (3 vs 5 mm length) was assessed. METHODS: Forty precut
      8.-mm-diameter donor posterior buttons were used in this study. Thirty-five
      buttons were inserted through a limbal incision of either 3 or 5 mm length into
      the anterior chamber of cadaver eyes and then removed through an open sky
      technique without further trauma. Five buttons that were trephined but not
      inserted served as a control group. Vital dye staining and computer digitized
      planimetry were used to analyze the tissue and quantify the total damaged area
      over the entire endothelial surface. Five buttons for each of 7 insertion
      techniques were used. The 8 tissue groups evaluated were as follows: group 1:
      control group of trephination only, with no insertion; group 2: forceps with
      folded tissue through 5-mm incision; group 3: suture pull through of nonfolded
      tissue through a 5-mm incision; group 4: forceps pull through of Busin glide
      folded tissue through a 5-mm incision; group 5: forceps with folded tissue
      through a 3-mm incision; group 6: suture pull through with folded tissue through
      a 3-mm incision; group 7: suture pull through with nonfolded tissue through a 3
      mm incision; and group 8: forceps pull through of Busin glide folded tissue
      through a 3-mm incision. RESULTS: The control group demonstrated 9% +/- 2%
      peripheral cell damage from simple trephination of the tissue but without
      insertion. In the 5-mm incision surgeries, forceps insertion (group 2) caused 18%
      +/- 3% loss, suture pull-through insertion (group 3) caused 18% +/- 2% loss, and
      Busin glide pull through (group 4) caused 20% +/- 5% loss. There were no
      significant differences in damage between any of the 5-mm incision group
      techniques (P > 0.99). In the 3-mm incision surgeries, forceps insertion (group
      5) caused a 30% +/- 3% loss, pull through with folded tissue (group 6) caused 30%
      +/- 5% loss, pull through with nonfolded tissue (group 7) caused 56% +/- 4% loss,
      and Busin glide pull through (group 8) caused a 28%+/- 5% loss. There was no
      difference in damage among the 3-mm groups (P > 0.96), with the exception of
      group 7 where pulling the unfolded tissue through a 3-mm incision was
      significantly worse than all other techniques (P < 0.001). There was
      significantly greater cell area damage in the 3-mm groups (36%) than in the 5-mm
      groups (19%) (P <0.001). Large patterns of striae with cell loss were seen in the
      3-mm groups emanating from the peripheral traction site, regardless of whether
      the traction to pull the tissue through the incision and into the chamber was
      generated by a suture or cross-chamber forceps. Direct forceps insertion caused
      circular patterns of injury at the tip compression site regardless of incision
      size, but this damage was multiplied and exacerbated by insertion through a
      smaller incision. CONCLUSIONS: Smaller size (3 mm) incisions for EK surgery
      result in greater acute endothelial area damage than larger size (5 mm)
      incisions. Pull-through insertion techniques through a 5-mm incision seem
      equivalent in the amount of induced area damage to that of forceps insertion.
      Compressive injury from the incision appeared less when the tissue was folded
      than when not folded. Insertion with any technique through a 3-mm incision
      resulted in larger areas of endothelial damage. All these iatrogenic death zones
      outside the central endothelial area would be missed clinically by standard early
      specular microscopy after EK surgery.

PMID- 19092401
TI  - Deep anterior lamellar keratoplasty after Intacs implantation in patients with
      keratoconus.
AB  - PURPOSE: To evaluate the clinical outcomes of deep anterior lamellar keratoplasty
      (DALK) in patients with unsatisfactory vision after intrastromal corneal ring
      segment (ICRS) implantation for keratoconus refractive correction. METHODS:
      Prospective interventional case series. Five patients with consecutive
      keratoconus and poor visual outcome after ICRS implantation underwent DALK Big
      bubble technique. Three patients had ICRS explanted several months before
      lamellar graft surgery because of late postoperative complications; the other 2
      had ring segments in place at the time of DALK. RESULTS: Average preoperative
      logarithm of the minimum angle of resolution (logMAR) uncorrected visual acuity
      was 1.5 +/- 0.685 (20/800) and 0.74 +/- 0.427 (20/114) at the end of the follow
      up. Mean preoperative logMAR best-corrected visual acuity was 0.56 +/- 0.089
      (20/70) and 0.12 +/- 0.044 (20/25) at the last examination. Mean MRSE changed
      from -8.75 +/- 6.74 diopters (D) preoperatively to -3.35 +/- 2.302 D
      postoperatively. Mean topographic astigmatism and mean topographic keratometry
      (K) varied from 3.96 +/- 2.197 and 50.06 +/- 3.965 D preoperatively to 1.72 +/-
      1.147 and 42.34 +/- 2.356 D postoperatively, respectively. No operative
      complications occurred. One patient developed stromal rejection that regressed
      after topical steroid therapy. CONCLUSIONS: DALK may be proposed in alternative
      to penetrating keratoplasty for the treatment of patients with keratoconus with
      poor visual result after ICRS implantation. DALK Big bubble technique may be
      carried out with ICRS in place. Visual and refractive outcomes are comparable
      with standard penetrating keratoplasty in patients with keratoconus.

PMID- 19092402
TI  - The prevalence and pathogenicity of Propionibacterium acnes keratitis.
AB  - PURPOSE: To study the prevalence, pathogenicity, and virulence of
      Propionibacterium acnes keratitis. METHODS: All cases of infectious keratitis
      submitted to the microbiologic laboratory of the New York Eye and Ear Infirmary
      between January 1, 2003, and April 6, 2006, were reviewed. Those cases in which
      P. acnes was recovered from culture were collected, and the medical records
      studied in depth. RESULTS: Of 1555 cultures submitted to the microbiology
      laboratory, 1329 (85.5%) were positive for growth. One hundred twenty four (9.3%)
      of the 1329 cases yielded P. acnes in at least 1 culture medium. Seventy eight
      (62.9%) of 124 cases had not been pretreated with antibiotics before culture, and
      66.7% of the nonpretreated ulcers were monomicrobial (P. acnes only). Fifty one
      (65.4%) of 78 cases of the nonpretreated corneal ulcers presented with a cellular
      reaction in anterior chamber, 12 (15.4%) with a hypopyon (6 were monomicrobial),
      21 (26.9%) had stromal thinning (12 of which were monomicrobial), and 2 (2.6%)
      progressed to perforation (both polymicrobial). Corneal ulcers associated with P.
      acnes tended to be small (66.7%) and were widely distributed: central (n = 17,
      21.8%), paracentral (n = 44, 56.4%), and peripheral (n = 17, 21.8%). The most
      common risk factors were contact lens wear and previous history of ocular
      surgery. Three of the 78 nonpretreated patients were unresponsive to medical
      treatment and required surgery for keratitis. CONCLUSION: This study provides
      evidence that P. acnes is a frequent cause of bacterial keratitis and may cause
      significant morbidity.

PMID- 19092403
TI  - Keratoconus in the Medicare population.
AB  - PURPOSE: To investigate the population-based prevalence of keratoconus in US
      individuals aged 65 years and older. DESIGN: Multiyear retrospective cross
      sectional claims analysis. METHODS: Fee-for-service claims from a 5% national
      sample of Medicare beneficiaries aged 65 years and older were reviewed. Claims
      records were queried on an annual basis for the years 1999 through 2003 for ICD-9
      codes specific to keratoconus. The number of beneficiaries with keratoconus
      related claims was counted for each calendar year. RESULTS: The number of
      beneficiaries receiving care for keratoconus rose steadily from 15.7/100,000
      beneficiaries in 1999 to 18.5/100,000 in 2003, averaging 17.5/100,000 across the
      5 years of the study. Keratoconus rates declined with increasing age but did not
      differ by gender. Keratoconus care was more prevalent in whites than in other
      races. CONCLUSIONS: Keratoconus is an uncommon disease in the Medicare
      population. Longitudinal analysis of Medicare claims data may provide a useful
      tool for monitoring uncommon diseases, such as keratoconus, in the elderly.

PMID- 19092404
TI  - Pterygium recurrence after excision with conjunctival autograft: a comparison of
      fibrin tissue adhesive to absorbable sutures.
AB  - PURPOSE: To evaluate the rate of recurrence after pterygium excision with
      conjunctival autograft (CAG) using Tisseel fibrin tissue adhesive versus
      absorbable sutures. MATERIALS AND METHODS: Forty-seven eyes of 42 patients who
      had undergone primary pterygium excision surgery with CAG were retrospectively
      reviewed. The study group, CAG adhered using Tisseel tissue adhesive (n = 27),
      were compared with the control group, CAG adhered using absorbable sutures (n =
      20). Postoperative courses were followed for 22-36 months after surgery. Rates of
      recurrence were compared using logistic regression. Recurrence was defined as
      regrowth of fibrovascular tissue 1 mm past the corneoscleral limbus. RESULTS: The
      recurrence rate in the Tisseel group was 3.7% compared with 20% in the sutured
      group (P = 0.035). Recurrence rate in the Tisseel group was comparable to
      previously reported rates for CAG with sutures in the literature. There was a
      significant inverse relationship between age and rate of recurrence overall (P =
      0.025). There was no difference in time to recurrence between the groups -- with
      an average time to recurrence of 3.13 months. CONCLUSIONS: In a predominantly
      Southern California population where there is an overall higher rate of pterygium
      recurrence, Tisseel tissue adhesive may improve surgical outcomes with equal to
      or lower long-term recurrence rates than previously reported.

PMID- 19092405
TI  - Conjunctival impression cytology, ocular surface, and tear-film changes in
      patients treated with systemic isotretinoin.
AB  - PURPOSE: To evaluate the ocular surface changes and tear-film functions in
      patients treated with systemic isotretinoin. METHODS: Fifty subjects treated with
      0.8 mg/kg oral isotretinoin were enrolled in this prospective clinical trial. All
      patients underwent a full ophthalmoscopic examination before, during, and after
      treatment with isotretinoin. Ocular surface changes of the cell content of the
      surface conjunctival epithelium were evaluated by conjunctival impression
      cytology and tear-film functions using the Schirmer test, anesthetized Schirmer
      test, tear breakup time, and rose bengal staining. Subjective ocular complaints
      were scored with an Ocular Surface Disease Index questionnaire. RESULTS: There
      were no significant differences observed in average Schirmer test scores for
      patients before, during, or after isotretinoin treatment. Mean anesthetized
      Schirmer test scores and tear breakup time decreased significantly during
      treatment (P < 0.001). Mean impression cytology scores, Ocular Surface Disease
      Index scores, and rose bengal staining scores increased significantly during
      treatment (P < 0.05, P < 0.001 and P < 0.001, respectively). Blepharitis was seen
      in 36% of patients. All abnormal findings disappeared 1 month after the cessation
      of treatment. CONCLUSIONS: Conjunctival epithelial cells, tear basal secretion,
      and tear quality are markedly affected in patients during systemic treatment with
      isotretinoin (0.8 mg/kg). Ocular adverse effects of isotretinoin are generally
      not serious and are reversible after discontinuation.

PMID- 19092406
TI  - Living-related conjunctival-limbal allograft for chronic or delayed-onset mustard
      gas keratopathy.
AB  - PURPOSE: To determine the long-term outcomes of living-related stem cell
      transplantation in patients with delayed or chronic mustard gas keratopathy
      (MGK). MATERIALS AND METHODS: In this noncomparative interventional case series,
      21 consecutive patients with advanced delayed or chronic MGK received living
      related conjunctival-limbal allograft and were followed up for at least 1 year.
      All subjects received immunosuppression with systemic cyclosporine. Main outcome
      measures were reduction of subjective complaints, corneal epithelial healing, and
      regression of corneal neovascularization adjacent to the transplant area.
      RESULTS: Twenty-five eyes of 21 patients (all male), including 4 patients who
      received bilateral grafts, were operated. Mean age at the time of surgery was
      35.8 +/- 3.8 years, mean interval between mustard gas exposure and surgery was
      12.2 +/- 3.5 years, and mean follow-up was 37.2 +/- 18.5 months. Average size of
      the donor lenticule was 71.16 +/- 17.34 degrees. Simultaneous penetrating and
      lamellar keratoplasty were performed in 5 and 2 eyes, respectively. All patients
      consistently reported marked subjective improvement. Mean time for epithelial
      healing was 7.76 +/- 3.2 days. Visual acuity was 1.35 +/- 0.81 LogMAR before
      surgery, which improved to 0.59 +/- 0.34 LogMAR 3 months after the procedure (P <
      0.001). Mean visual acuity at final examination was 0.82 +/- 0.49 LogMAR (P =
      0.001). Acute stem cell rejection was observed in 10 (40%) eyes, which improved
      by increasing the dose of topical and systemic steroids. Chronic stem cell
      rejection was diagnosed in 8 (32%) eyes, which led to failure in 5 (20%) eyes.
      CONCLUSIONS: Living-related conjunctival-limbal allograft is effective in
      stabilizing the ocular surface in patients with delayed or chronic MGK.

PMID- 19092407
TI  - Antibacterial activity of preservative-free topical anesthetic drops in current
      use in ophthalmology departments.
AB  - AIM: The antibacterial effect of topical anesthetics may lead to false-negative
      cultures from corneal specimens of bacterial keratitis. This in vitro study
      compared the antibacterial effect of 3 unpreserved topical anesthetics to
      indicate the most appropriate agent for corneal scrapes. METHODS: Four bacterial
      strains (Staphylococcus epidermidis, Staphylococcus aureus, Pseudomonas
      aeruginosa, and Streptococcus pneumoniae) derived from the most frequently
      isolated microorganisms from corneal ulcers were cultured from stored control
      stocks and clinical specimens. These strains were used to determine the minimum
      inhibitory concentration (MIC) of 3 preservative-free anesthetic eyedrops:
      proxymetacaine 0.5%, oxybuprocaine 0.4%, and tetracaine 1%. RESULTS: There was no
      inhibition of growth seen with proxymetacaine 0.5% (5000 microg/mL) with any of
      the organisms except S. epidermidis, which demonstrated an MIC of 2500 microg/mL
      (equivalent to a dilution of (1/2)). Tetracaine 1% (10,000 microg/mL) produced an
      MIC ranging between 625 and 1250 microg/mL, inhibiting all 4 strains at the
      commercially available dilution. Oxybuprocaine 0.4% (4000 microg/mL) resulted to
      be the second most inhibitory preparation with an MIC ranging between 1000 and
      2000 microg/mL. CONCLUSIONS: Currently used preservative-free topical anesthetics
      differ in bacterial growth inhibition. This in vitro study showed that
      proxymetacaine 0.5% is the least inhibitory on bacterial growth and therefore the
      most appropriate to be used before corneal scrapes.

PMID- 19092408
TI  - Corneal collagen cross-linking: a confocal, electron, and light microscopy study
      of eye bank corneas.
AB  - PURPOSE: The purpose of this study was to evaluate morphological changes induced
      by corneal collagen cross-linking in a human ex vivo cornea, using confocal,
      electron, and light microscopy. METHODS: The central epithelium was partially
      removed from ex vivo human corneal buttons. Riboflavin 0.1% solution was applied
      before ultraviolet A light treatment and then for every 2 minutes for 30 minutes
      while the corneas were exposed to ultraviolet A light at a wavelength of 370 nm
      and intensity of 3 mW/cm(2). Each cornea was evaluated using confocal, electron,
      and light microscopy. RESULTS: Confocal microscopy demonstrated normal-appearing
      corneas on their initial pretreatment examination, with reduced stromal detail.
      After treatment, a superficial layer of highly reflective spherical structures (4
      10 microm) was observed. Many of these hyperreflective structures appeared up to
      a depth of 300 microm. The remainder of the corneal stroma and endothelium
      appeared normal. Electron microscopy showed keratocyte apoptotic changes to a
      depth of 300 microm. No observable pathologic changes were seen on histology.
      CONCLUSIONS: Based on clinical studies, corneal cross-linking is a promising
      treatment that appears to be safe and to halt ectatic corneal disease
      progression. Initial European studies used animal models to extrapolate human
      protocols. In conjunction with clinical studies, we believe that human ex vivo
      corneal studies provide a means to evaluate the structural and morphological
      changes associated with this procedure, within human corneas, in a manner that
      cannot be accomplished in vivo.

PMID- 19092409
TI  - The resistance patterns of normal ocular bacterial flora to 4 fluoroquinolone
      antibiotics.
AB  - PURPOSES: The purposes of this study were to determine the normal ocular
      bacterial flora isolated from patients undergoing anterior segment surgery and to
      evaluate their in vitro susceptibility to ciprofloxacin, levofloxacin,
      gatifloxacin, and moxifloxacin. METHODS: During January 2006 to December 2006,
      conjunctival swabs taken from 385 eyes were inoculated onto 5% blood agar plates.
      The isolated bacteria were classified by analysis of 16s ribosomal DNA
      sequencing. Disk diffusion testing was performed in accordance with Clinical and
      Laboratory Standards Institute Performance Standards. RESULTS: Three hundred
      sixty-three microorganisms were isolated in 291 samples from 385 eyes. Gram
      positive species predominated (89.8%, 326 of the 363 isolates), and
      Staphylococcus epidermidis was the most frequently isolated organism, accounting
      for 60.6% (220 of the 363 isolates). For 293 gram-positive isolates, the
      prevalence rates of in vitro resistance to ciprofloxacin, levofloxacin,
      gatifloxacin, and moxifloxacin were 22.2% (65 isolates), 11.6% (34), 2.7% (8),
      and 5.1% (15), respectively. Two of the gram-negative isolates were resistant to
      only ciprofloxacin (5.4%, 2 of 37 isolates) and not to other fluoroquinolones. Of
      62 ciprofloxacin-resistant, coagulase-negative staphylococci, 32 (51.6%) showed
      coresistance to levofloxacin. Seven organisms were resistant to all the
      fluoroquinolones. CONCLUSIONS: Fluoroquinolones have activity against normal
      aerobic flora of the ocular surface. Normal ocular flora, especially gram
      positive species, has low resistance to the fourth-generation fluoroquinolones --
      gatifloxacin and moxifloxacin.

PMID- 19092410
TI  - Histologic evaluation of human posterior lamellar discs for femtosecond laser
      Descemet's stripping endothelial keratoplasty.
AB  - PURPOSE: To evaluate the histologic changes in corneal structure after
      femtosecond laser preparation of posterior lamellar discs, more specifically, the
      smoothness of the stromal bed and the accuracy of the predicted depth of the
      horizontal lamellar cut. MATERIALS AND METHODS: Nineteen human donor eyes
      unsuitable for transplantation were used. Femtosecond laser was used to prepare a
      horizontal lamellar cut in donor corneas at a depth of 400 microm. Transmission
      electron microscopy images were used to evaluate the changes in the corneal
      structure and to measure the damage zone. Scanning electron microscopy images
      were used to determine the relative depth of the horizontal lamellar cut, and the
      stromal bed was examined to determine the smoothness of the surface. RESULTS:
      Transmission electron microscopy images showed a mean damage zone of 6.8 +/- 3.1
      microm, which consisted of irregularly oriented collagen fibrils and electron
      dense granular material. The collagen lamellae, both anteriorly and posteriorly
      of the damaged zone, showed a regular parallel configuration. The relative depth
      of the horizontal lamellar cut as percentage of the total corneal thickness in
      the center and periphery was 70.4% +/- 4.5% and 55.6% +/- 5.9%. Scanning electron
      microscopy images of the stromal bed showed a relatively smooth surface.
      CONCLUSION: The femtosecond laser is effective to prepare a deep horizontal
      lamellar cut in a standardized method. The stromal bed is smooth and without
      extensive adjacent tissue damage. The is thinner in the center and thicker at the
      edges, which may produce a mild hyperopic shift after femtosecond laser-assisted
      Descemet's stripping endothelial keratoplasty.

PMID- 19092412
TI  - Salzmann nodules -- a possible new ocular manifestation of Crohn's disease: a
      case report.
AB  - PURPOSE: The purpose of this article was to describe an association between
      Salzmann nodules and Crohn's disease. METHODS: Single observational case report.
      RESULTS: Multiple bilateral Salzmann nodules were found in a 50-year-old woman
      with inactive Crohn's disease. Her visual acuity was 20/25 in OD and 20/20 in OS
      because of involvement of the midperipheral cornea. Intraocular pressure was
      significantly elevated in both eyes. However, there were no other signs of
      glaucoma. The rest of the ocular examination was unremarkable. CONCLUSIONS:
      Salzmann nodules may represent a distinct clinical sign of ocular involvement in
      Crohn's disease.

PMID- 19092411
TI  - New surgical strategy for corneal tattooing using a femtosecond laser.
AB  - PURPOSE: The purpose of this study was to describe a new method of femtosecond
      (FS) laser-assisted corneal tattooing and to report the results of this method in
      a case series. METHODS: The study involved 6 eyes of 6 patients with total or
      partial corneal opacity. An FS laser was used for lamellar dissection and to make
      a side cut with a hinge, creating a corneal flap. Laser parameters were adjusted
      depending on ocular condition and the location of the corneal opacity. After
      lifting the corneal flap, further lamellar dissection with a diamond blade was
      performed up to the periphery of the limbal area. Using a cannula, dye was
      injected into the lamellar stromal bed and the space of the lamellar dissected
      pocket in the limbus, after which the flap was repositioned. RESULTS: The design
      and application of the FS laser for dissection and flap creation were successful
      in all cases. There were no significant complications other than an incomplete
      cut under band keratopathy in 1 eye. The cosmetic effects were satisfactory in
      all cases. No patient complained of pain for more than 1 day after surgery.
      CONCLUSIONS: The advantages of the FS laser-assisted corneal tattooing include a
      customized design, speed, decreased pain, reduced risk of perforation, and good
      wound healing. This procedure provides improvements over current corneal
      tattooing techniques, although it is relatively expensive.

PMID- 19092413
TI  - Isolated unilateral congenital lacrimal gland agenesis presenting as filamentary
      keratopathy in a child.
AB  - Congenital lacrimal gland agenesis is extremely rare, and there are only a few
      cases reported in the literature. These cases involve bilateral lacrimal gland
      agenesis associated, in some instances, with salivary gland agenesis and
      abnormalities of the lacrimal puncta and canaliculi. This report, to our
      knowledge, presents the first documented case of unilateral lacrimal gland
      agenesis, resulting in unilateral filamentary keratopathy.

PMID- 19092414
TI  - Infliximab for the treatment of refractory progressive sterile peripheral
      ulcerative keratitis associated with late corneal perforation: 3-year follow-up.
AB  - PURPOSE: To report a case of refractory progressive sterile peripheral ulcerative
      keratitis (PUK) that resulted in late corneal perforation, despite good initial
      response to tumor necrosis factor-alpha inhibitor infliximab. METHODS: Review of
      the clinical course of a patient with progressive PUK treated with infliximab
      infusions of 3 mg/kg intravenously. RESULTS: A 72-year-old man presented with a
      visual acuity of 20/200 and a 5-month history of a progressive sterile PUK. More
      than 90% of the surface area previously unresponsive to 8 weeks of high-dose
      systemic steroid therapy healed within 1 week of the first infusion. After his
      second infusion, best-corrected visual acuity improved to 20/30(+2), with 2 small
      epithelial defects remaining. However, the remaining unhealed cornea thinned to
      an area of microperforation 6 weeks after his third dose, prompting an increase
      in dose frequency to every 4 weeks. One month after his fifth infusion, the area
      of ulceration healed completely. After his seventh infusion, the patient
      developed a deep venous thrombosis and infliximab was discontinued. After 10
      months of remission, clear corneal cataract surgery was performed. Three years
      after initial presentation, he remains in remission with a corrected visual
      acuity of 20/20. CONCLUSIONS: Infliximab was effective in rapidly arresting the
      progression of a sterile PUK in our patient. Optimal dosing for infliximab in PUK
      has not been established, and increasing dose frequency to every 4 weeks may be
      necessary. Despite a progressive PUK resulting in corneal perforation, treatment
      with infliximab and subsequent visual rehabilitation can result in sustained
      remission and an excellent visual outcome.

PMID- 19092415
TI  - Posterior lamellar disc dislocation into the vitreous cavity during descemet
      stripping automated endothelial keratoplasty.
AB  - We present a case of a dislocated posterior lamellar lenticule into the vitreous
      cavity during Descemet stripping automated endothelial keratoplasty. After
      insertion of the donor disc in a partially vitrectomized eye with partial iris
      loss, the graft dislocated into the vitreous cavity. With a standard 3-port
      vitrectomy and the help of perflourocarbon fluid, the graft was lifted into the
      anterior segment of the eye and firmly attached to the recipient cornea using
      liquid-air exchange. The postoperative follow-up was without complications. The
      cornea was clear at the third day after surgery without recurrent graft
      dislocation.

PMID- 19092416
TI  - Classic lattice corneal dystrophy associated with monoclonal gammopathy after
      exclusion of a TGFBI mutation.
AB  - PURPOSE: The purpose of this study was to report the association of phenotypic
      features characteristic of lattice corneal dystrophy (LCD) with a monoclonal
      gammopathy of undetermined significance (MGUS) after exclusion of a coding region
      mutation in transforming growth factor beta-induced (TGFBI) gene. DESIGN: Case
      report. METHODS: Slit-lamp examination and collection of DNA for TGFBI screening
      were performed. A systemic evaluation was also performed to evaluate for
      conditions associated with systemic amyloidosis. RESULTS: A 65-year-old man
      demonstrated bilateral linear branching corneal stromal opacities characteristic
      of classic LCD. No mutations were found in any of the 17 exons of TGFBI or in the
      intron-exon boundary regions. Four previously described single nucleotide
      polymorphisms were identified: c.698C>G (p.Leu217Leu; rs1442), c.1028A>G
      (p.Val327Val; rs1054124), c.1416C>T (p.Leu472Leu; rs1133170), and c.1667T>C
      (p.Phe540Phe; rs4669). Serum protein electrophoresis revealed the presence of a
      monoclonal spike, and based on the results of additional investigations, the
      patient was diagnosed with MGUS. CONCLUSIONS: Although the presence of bilateral
      thin branching lattice lines in the corneal stroma is characteristic of classic
      LCD, this distinctive phenotype may not be associated with a TGFBI coding region
      mutation but instead with a myeloproliferative disorder such as MGUS. Therefore,
      appropriate genetic and serologic testing should be performed in patients with a
      late-onset LCD phenotype in the absence of a positive family history.

PMID- 19092417
TI  - Progression of essential iris atrophy studied with confocal microscopy and
      ultrasound biomicroscopy: a 5-year case report.
AB  - PURPOSE: The purpose of this study was to report the progression of the
      iridocorneal endothelial syndrome during a 5-year period in a patient with the
      essential iris atrophy variant using confocal microscopy and ultrabiomicroscopy
      (UBM). METHODS: A 47-year-old woman was referred to us in January 2002 with
      suspected iridocorneal endothelial syndrome. Examination of both eyes included
      visual acuity, biomicroscopy, intraocular pressure measurement, gonioscopy,
      visual field test, and UBM. Afterward, she was examined yearly and confocal
      microscopy performed. RESULTS: Visual acuity was 20/20 in both eyes. Examination
      of the right eye revealed endothelial degeneration, peripheral anterior
      synechiae, and iris atrophy around the pupil that appeared displaced to the
      temporal side. Biomicroscopy of the left eye was unremarkable. Posterior segment
      was normal in both eyes. UBM of the right eye showed thickening of the iris
      adherent to the corneal endothelium. Diagnosis of essential iris atrophy was
      confirmed. One year later, the right eye showed increasing iridoendothelial
      adherences confirmed by UBM. Confocal microscopy revealed endothelial cell
      abnormalities and groups of endothelial "epithelium-like" cells with
      hyperreflective nuclei. In April 2007, the pupil appeared more temporally
      dislocated. UBM showed more extended synechiae. Confocal microscopy displayed
      hyporeflective opacities in the endothelial layer and many grouped keratocytic
      clusters in the posterior stroma. No alteration of the intraocular pressure and
      visual field was found during the follow-up. CONCLUSIONS: UBM and confocal
      microscopy permit observation of any corneal and iridocorneal angle changes and
      evaluation of essential iris atrophy progression.

PMID- 19092418
TI  - Topical bevacizumab eyedrops for limbal-conjunctival neovascularization in
      impending recurrent pterygium.
AB  - PURPOSE: To report a case of impending recurrent pterygium treated with topical
      bevacizumab eyedrops. METHODS: A 53-year-old woman with impending recurrent
      pterygium was treated with topical bevacizumab eyedrops (25 mg/mL) administered 4
      times daily for 3 weeks. Two months previously, she had undergone excision of a
      primary ptergyium in the same eye by bare sclera recision and application of
      mitomycin C. RESULTS: Treatment with topical bevacizumab for 3 weeks produced
      prominent regression of limbal-conjunctival neovascularization. At 6-month follow
      up, no recurrent pterygium was noted. Symptoms were resolved with no ocular
      irritation, burning, or any systemic adverse effects. CONCLUSIONS: These data
      suggest that off-label short-term use of topical bevacizumab may be effective to
      prevent recurrence in a patient with impending recurrent pterygium. We believe
      that this is the first known successful use of topical bevacizumab in such a
      patient.

PMID- 19092419
TI  - Unilateral Candida parapsilosis interface keratitis after laser in situ
      keratomileusis: case report and review of the literature.
AB  - PURPOSE: To describe a rare case of early-onset Candida parapsilosis infection
      after laser in situ keratomileusis (LASIK) and review the published reports of
      post-LASIK fungal infections. METHODS: A 32-year-old woman presented with
      interface infiltration in the central interface in the right eye 2 days after
      LASIK surgery. The right eye flap was lifted, and the opacities were scraped. Two
      days later, a 3- x 3-mm-dense oval opacity and diffuse hazes were noted. Surgical
      intervention was arranged because of suspicion of interface infectious keratitis.
      RESULTS: After an apparent post-LASIK keratitis with related interface
      inflammation failed to respond to medical therapy, corneal culture results were
      positive for C. parapsilosis 2 weeks 6 days after presentation. The patient was
      started on topical drops of amphotericin B 0.15% every hour after the smear
      showed the presence of yeast. The opacities decreased, and the topical antifungal
      drops were tapered. One month later, her uncorrected visual acuity recovered to
      20/20. CONCLUSIONS: Candida parapsilosis interface keratitis after LASIK may
      occur in the early phase. Early diagnosis and proper treatment can result in good
      outcome.

PMID- 19092420
TI  - New-onset herpes simplex virus keratitis after cataract surgery.
AB  - We report the case of a 34-year-old man who had uncomplicated cataract surgery in
      his left eye. Medical history was significant for atopic dermatitis, requiring
      oral immunosuppressive medications. Two days after the surgery, the patient
      presented with pain, photophobia, decreased vision, and a small corneal abrasion.
      On postoperative day 5, the patient returned with left upper lid vesicular
      lesions and 2 corneal dendrites. Corrected vision was 20/100 OS, with intraocular
      pressure of 18 mm Hg and 1+ pigmented cells in the anterior chamber. Cultures of
      the lid lesions revealed herpes simplex virus (HSV) type 1. The patient was
      placed on oral acyclovir 800 mg 5 times a day. By day 8, the dendrites had
      resolved, and by day 15, the lid lesions healed over. HSV keratitis is an
      uncommon complication after cataract surgery. Ophthalmologists should be aware of
      the possibility of developing HSV keratitis even after the most routine cataract
      extraction.

PMID- 19092421
TI  - Peripheral ulcerative keratitis after trabeculectomy in a patient with rheumatoid
      arthritis.
AB  - PURPOSE: To report the unusual occurrence of peripheral ulcerative keratitis, 10
      days after trabeculectomy in a 35-year-old patient with rheumatoid arthritis
      (RA). METHODS: Observational case report. RESULTS: A 35-year-old patient with RA
      and secondary Sjogren disease underwent an uneventful fornix-based
      trabeculectomy. Ten days after surgery, slit-lamp examination revealed a
      peripheral corneal ulcer extending from 5- to 7-o'clock positions with a
      surrounding inflammatory infiltrate and adjacent conjunctival injection. The
      ulcer was treated with systemic and topical steroids, antibiotic eyedrops,
      artificial tears, and a bandage soft contact lens. Since then, corneal re
      epithelialization started and the patient's symptoms subsided. The ulcer improved
      steadily within 2 months while the patient used a soft contact lens. The ulcer
      did not reoccur in the 18 months follow-up while the patient remained under
      systemic treatment. CONCLUSION: This report highlights the importance of careful
      examination and close postoperative follow-up in patients with RA undergoing any
      intraocular surgery, to diagnose a possible development of peripheral ulcerative
      keratitis. Although the incidence is rare, prompt diagnosis of the peripheral
      ulceration is essential because if untreated it may seriously affect patient's
      vision.

PMID- 19092422
TI  - Corneal deposits after topical tosufloxacin in a patient with poor tear
      secretion.
AB  - PURPOSE: To report on severe visual impairment in a patient with decreased tear
      secretion in whom dense corneal deposits resulted from tosufloxacin treatment
      after cataract surgery. METHODS: An 86-year-old woman complained of blurred
      vision in the left eye. She had been treated with topical applications of
      tosufloxacin, betamethasone, and diclofenac sodium, all administered 4 times a
      day as a regimen lasting for 1 month after cataract surgery. In that eye, the
      best spectacle-corrected visual acuity was 20/200 due to the dense deposits on
      the cornea. The Schirmer test showed a decrease in basic tear secretion (right
      eye 2 mm, left eye 1 mm). We removed these deposits surgically and analyzed them
      by infrared spectrophotometry. RESULTS: The best spectacle-corrected visual
      acuity markedly improved, to 20/25, after surgical removal of the deposits in the
      left eye. The spectrophotometric pattern of the deposits was consistent with that
      of tosufloxacin. CONCLUSIONS: Topical application of tosufloxacin may lead to
      fluoroquinolone drug deposition on the cornea, especially when an antibiotic drug
      has been used continuously in patients with poor tear secretion.

PMID- 19092423
TI  - Alternaria keratitis: clinical presentation and resolution with topical
      fluconazole or intrastromal voriconazole and topical caspofungin.
AB  - PURPOSE: The purpose of this study was to describe the clinical presentation of 3
      cases of Alternaria keratitis and their response to medical therapy. METHODS: All
      cases of Alternaria keratitis diagnosed and treated at the University of Illinois
      Eye and Ear Infirmary from 1999 to 2007 were reviewed for clinical presentation,
      antifungal therapy, and final visual acuity. RESULTS: Three cases of Alternaria
      keratitis were identified. All patients presented with an indolent steroid
      treated keratitis and a history of recent cataract surgery, agricultural trauma,
      or contact lens wear. None of the patients responded to natamycin, and 1 also
      failed to respond to topical and systemic voriconazole. Patients responded
      rapidly to either topical fluconazole 0.02% or a combination of intrastromal
      voriconazole and topical caspofungin 0.5%. Final visual acuity ranged between
      20/15 and 20/25. CONCLUSIONS: Alternaria keratitis has a varied clinical
      presentation and may present without macroscopic pigmentation. In vitro
      sensitivity testing may be helpful in directing therapy for Alternaria keratitis,
      but clinical response should be monitored as the primary endpoint. Response to
      natamycin was poor, but successful resolution with topical fluconazole or
      intrastromal voriconazole and topical caspofungin with preservation of good
      visual acuity was possible.

PMID- 19092424
TI  - Streptococcus bovis causing perforating corneal ulcer.
AB  - PURPOSE: The purpose of this study was to report the first case of Streptococcus
      bovis causing a perforating corneal ulcer in a healthy adult. METHODS:
      Observational case report. RESULTS: A healthy 77-year-old man presented with
      rapidly progressing corneal ulcer, resulting in perforation within 4 days.
      Preoperative and operative cultures isolated the same organism, S. bovis,
      susceptible only to vancomycin and ceftriaxone. The patient underwent a
      successful corneal transplantation, with histopathology revealing full-thickness
      necrosis and scattered bacteria. CONCLUSIONS: Although a rare pathogen in ocular
      infections, we report a case of devastating corneal infection caused by S. bovis
      and highlight consideration of this pathogen in rapidly progressing corneal
      ulcers.

PMID- 19092425
TI  - Fresh frozen plasma treatment of ligneous conjunctivitis: use of heparin and
      allogeneic serum.

PMID- 19092426
TI  - Dendriform filamentary keratopathy.

PMID- 19092427
TI  - Increased glucose level in aqueous changes the posterior corneal power.

PMID- 19092429
TI  - From the editor: it is no secret that national politics and economics play a
      significant role in the disparities experienced by border communities in areas
      such as employment, education, and healthcare.

PMID- 19092430
TI  - The health and well-being of individuals, families, and communities that make up
      the US-Mexico border region. Foreword.

PMID- 19092431
TI  - Healthcare access and barriers for unauthorized immigrants in El Paso County,
      Texas.
AB  - This article presents a large body of qualitative material on healthcare access
      and barriers for unauthorized immigrants living in the US-Mexico borderlands. The
      focus is on active sequences of health-seeking behavior and barriers encountered
      in them. Barriers include direct legal mandates, fear of authorities, obstacles
      to movement by immigration law enforcement, interaction of unauthorized legal
      status with workplace and household relations, and hierarchical social
      interactions in healthcare and wider social settings. At the same time, important
      resilience factors include community-oriented healthcare services and the
      learning/confidence-building process that enable the unauthorized to connect to
      such services. An important finding is that barriers are not discrete factors but
      rather occur as webs that make solution of challenges more difficult than
      individual barriers alone. Outcomes include incomplete sequences of care,
      especially breakdowns in complex diagnoses, long-term treatment, and monitoring
      of chronic conditions.

PMID- 19092432
TI  - Individual, social, and environmental barriers to and facilitators of physical
      activity among Latinas living in San Diego County: focus group results.
AB  - The purpose of this study was to examine the barriers to and facilitators of
      physical activity (PA) relevant to a faith-based community living in a border
      region. Two focus groups were conducted with 25 Latina churchgoers. Latinas
      identified barriers to PA that included individual (eg, lack of motivation and
      time, language, economics, social support, family/household responsibilities),
      sociocultural (eg, fear of border patrol, machismo, and neighborhood safety), and
      environmental barriers (eg, traffic-related and dogs). Facilitators of PA were PA
      knowledge, child care, time management, and advocacy skills. The authors
      concluded that a church-based multilevel intervention targeting Latinas may be
      ideal for promoting PA and facilitating environmental changes.

PMID- 19092433
TI  - An exploration of Hispanic workers' perspectives about risks and hazards
      associated with orchard work.
AB  - Orchard workers are a population at risk for serious and disabling occupational
      injuries and illnesses. The purpose of this descriptive, exploratory study was to
      gather information about orchard workers' perceptions and experiences related to
      their work to better understand factors that contribute to their occupational
      risk. The sample consisted of 180 Hispanic orchard workers from 3 counties in
      Washington State; about a third of these reported at least 1 occupational injury.
      A Likert scale was used to gather workers' perceptions about individual, work
      related, and environmental factors that have the potential to contribute to the
      occurrence of occupational injuries and illnesses. Psychosocial factors emerged
      as particularly important influences on workers' health and safety. Injured
      workers were more likely than noninjured workers to feel (1) that they are more
      likely to be fired, (2) that the "boss cares more about the fruit than the
      worker," (3) that their employer was demanding, and (4) that orchard work was
      dangerous. There is a compelling need to develop and test interventions that
      address factors that adversely affect orchard workers' health and safety.

PMID- 19092434
TI  - Promotores as partners in a community-based diabetes intervention program
      targeting Hispanics.
AB  - Promotores, community health workers, are a pivotal component of LA VIDA, a
      diabetes intervention program targeting Hispanics who have or are at risk for
      diabetes. The purpose of this qualitative study was to evaluate the role of LA
      VIDA promotores in reducing diabetes health disparities among Hispanics in
      southwestern New Mexico. Interviews with 17 promotores revealed that they
      effectively relate to their clients as fellow community members who understand
      the culture and often know clients and their families. Promotores facilitate
      access to healthcare and social services, enroll participants in educational and
      physical activities, support lifestyle changes, and conduct LA VIDA intervention
      and prevention activities. Through their education and advocacy for clients,
      promotores act as healthcare navigators for numerous health and social services
      while providing support for personal and family issues. Their role transcends
      that of educator and advocate for clients as they develop community partnerships
      and collaborate with community groups to implement health-related activities. In
      essence, promotores become community partners in their efforts to build capacity
      and promote healthy Hispanic communities.

PMID- 19092435
TI  - Benefits of increased home-visitation services: exploring a case management
      model.
AB  - This study examined outcome measures of a home-visitation program that provided
      services to first-born children and their parents. Home-visitation workers
      conducted pretest-posttest assessments for prenatal and postpartum periods for
      109 families. Families were assessed using the Revised North Carolina Family
      Assessment Scale. Paired sample t tests were used to assess effect. Ordinary
      least squares regression measured effect of increased home-visitation services on
      family well-being. In this study, program participants displayed significantly
      higher posttest scores on social support, caregiver characteristics, family
      interaction measures, and a reduction in personal problems affecting parenting.
      Improved scores were significantly related to increased numbers of home
      visitation services. The results are promising as participants were observed to
      make positive improvements in family resiliency.

PMID- 19092436
TI  - Community-acquired methicillin-resistant Staphylococcus aureus: not just a spider
      bite.
AB  - Methicillin-resistant Staphylococcus aureus has been commonly known to be found
      in hospital or healthcare settings; however, increased prevalence within the
      community has posed a concern to providers with treatment management and costs.
      Community-acquired methicillin-resistant Staphylococcus aureus infections
      typically present as skin and soft tissue infections but do not respond to
      typical skin and soft tissue infection treatment. Methicillin-resistant
      Staphylococcus aureus can also lead to more serious systemic infections, even in
      the healthy individual. With this, the healthcare provider must be aware of the
      prevalence and populations with increased risk and the recommended treatment and
      education. Assessment, diagnosis, education, and treatments must be appropriate
      and meet the needs of the individual. Therefore, this article provides current
      assessment and treatment recommendations through a typical case study.

PMID- 19092438
TI  - Legal update: living with the Genetic Information Nondiscrimination Act.
AB  - The Genetic Information Nondiscrimination Act of 2008 promises to make genetic
      discrimination illegal in the contexts of employment and health insurance. The
      promises of the law may be difficult to fully deliver. This article will examine
      some of the more important provisions that offer protection against genetic
      discrimination and the major shortcomings of the legislation. It concludes that
      the Genetic Information Nondiscrimination Act is an important piece of civil
      rights legislation, but it is not fully protective of individuals who are worried
      about genetic discrimination in employment or insurance.

PMID- 19092439
TI  - Abacavir hypersensitivity: a model system for pharmacogenetic test adoption.
AB  - A pharmacogenetic marker for abacavir hypersensitivity is rapidly being
      incorporated into routine medical practice following demonstration of strong
      clinical utility in pivotal clinical studies. As one of the few pharmacogenetic
      markers that have crossed from research tools to clinical adoption and
      utilization, the abacavir hypersensitivity pharmacogenetic marker provides a
      great model for demonstration of factors that are critical to successful
      pharmacogenetic test adoption. Several examples of novel diagnostic test
      implementation are reviewed with focus on factors that are critical to
      translation into clinical practice. Other pharmacogenetic markers that have not
      yet been integrated into routine clinical care are discussed and reasons for
      their lack of acceptance are suggested.

PMID- 19092437
TI  - Clinical practice and genetic counseling for cystic fibrosis and CFTR-related
      disorders.
AB  - Cystic fibrosis transmembrane conductance regulator-related disorders encompass a
      disease spectrum from focal male reproductive tract involvement in congenital
      absence of the vas deferens to multiorgan involvement in classic cystic fibrosis.
      The reproductive, gastrointestinal, and exocrine manifestations of cystic
      fibrosis transmembrane conductance regulator deficiency are correlated with CFTR
      genotype, whereas the respiratory manifestations that are the main cause of
      morbidity and mortality in cystic fibrosis are less predictable. Molecular
      genetic testing of CFTR has led to new diagnostic strategies and will enable
      targeting of molecular therapies now in development. Older diagnostic methods
      that measure sweat chloride and nasal potential difference nonetheless remain
      important because of their sensitivity and specificity. In addition, the
      measurement of immunoreactive trypsinogen and the genotyping of CFTR alleles are
      key to newborn screening programs because of low cost. The multiorgan nature of
      cystic fibrosis leads to a heavy burden of care, thus therapeutic regimens are
      tailored to the specific manifestations present in each patient. The variability
      of cystic fibrosis lung disease and the variable expressivity of mild CFTR
      alleles complicate genetic counseling for this autosomal recessive disorder.
      Widespread implementation of newborn screening programs among populations with
      significant cystic fibrosis mutation carrier frequencies is expected to result in
      increasing demands on genetic counseling resources.

PMID- 19092441
TI  - The impact of direct-to-consumer marketing of cancer genetic testing on women
      according to their genetic risk.
AB  - PURPOSE: To assess the impact of direct-to-consumer marketing for genetic testing
      among women of varying genetic risk for breast and ovarian cancer. METHODS:
      Telephone surveys were conducted with 315 women in Denver, Colorado, one target
      audience for the Myriad BRACAnalysis ad campaign. Genetic risk was determined
      from personal and family history and grouped by probability of having a BRCA1/2
      mutation (low <5%, moderate 5-<10%, high > or =10%). RESULTS: High-risk women
      were more knowledgeable about BRACAnalysis and more likely to recall the media
      ads than were low-risk women (60 vs. 39%, P < 0.01). After seeing the ads, about
      40% of women were more interested in testing and about 10% expressed increased
      worry about developing breast or ovarian cancer. Women across all risk groups
      overstated the benefits and appropriateness of testing. An equal percentage of
      high- and low-risk women (51 and 60%) felt that they would benefit from genetic
      testing. CONCLUSION: The campaign effectively reached a large audience. Concern
      about breast cancer was not appreciably increased. A large percentage of low-risk
      women (not candidates for testing) expressed interest in testing, suggesting the
      campaign was too broad. A campaign targeted at high-risk women, who may benefit
      from testing might be preferred.

PMID- 19092440
TI  - Relation of familial patterns of coronary heart disease, stroke, and diabetes to
      subclinical atherosclerosis: the multi-ethnic study of atherosclerosis.
AB  - PURPOSE: To investigate the possibility that family history beyond early-onset
      coronary heart disease might contribute to coronary heart disease susceptibility,
      we studied associations between additional family history and the coronary artery
      calcium score. METHODS: Associations between coronary artery calcium score and
      self-reports of coronary heart disease, stroke, and diabetes in first-degree
      relatives of 5264 nondiabetic subjects were assessed using logistic and linear
      regression adjusting for risk factors; adjusted mean coronary artery calcium
      score estimates were determined by pooling results. RESULTS: Family history of
      coronary heart disease alone and in combination with diabetes and/or stroke was
      significantly associated with a positive coronary artery calcium score compared
      with no family history with odds ratios ranging from 1.7 (95% CI: 1.3-2.3) to 1.9
      (95% CI: 1.6-2.3) and adjusted mean coronary artery calcium score estimates
      ranging from 137 (95% CI: 101-173) to 184 (95% CI: 143-226). Associations between
      family history of coronary heart disease and coronary artery calcium score were
      significant regardless of age at onset, sex, lineage, or number of relatives with
      coronary heart disease. The association between family history of diabetes only
      and coronary artery calcium score was also significant (OR, 1.3; 95% CI: 1.1-1.7)
      with an adjusted mean coronary artery calcium score estimate of 122 (95% CI: 93
      151). Generally, family history of stroke had nonsignificant associations with
      coronary artery calcium score. CONCLUSIONS: Numerous family history variables in
      addition to early-onset coronary heart disease are associated with subclinical
      atherosclerosis. Our results have implications for improving coronary heart
      disease risk assessment.

PMID- 19092443
TI  - Population screening in a Druze community: the challenge and the reward.
AB  - PURPOSE: The Druze community is characterized by consanguinity and endogamy, and
      by reluctance to genetic testing and technological interventions for the
      prevention of birth defects. Multiple patients with four rare and severe inborn
      errors of metabolism cerebrotendinous xanthomatosis, prolidase deficiency,
      argininosuccinate lyase deficiency, and carbamyl phosphate synthetase I
      deficiency were identified in an isolated Druze village in northern Israel. The
      aims of this study were to identify couples at risk for four inherited diseases,
      and to prevent birth defects in a community presenting religious and cultural
      obstacles to genetic testing. METHODS: A genetic screening and counseling program
      in a high-risk community. RESULTS: The 1425 residents who attended group genetic
      counseling sessions between 2003 and 2007 consented to genetic testing. We
      identified 217 carriers for either one or two disease causing mutations. High
      carrier frequencies for cerebrotendinous xanthomatosis, prolidase deficiency,
      argininosuccinate lyase deficiency, and carbamyl phosphate synthetase I
      deficiency were identified as 1:11, 1:21, 1:41, and 1:95, respectively. Fifty
      eight percent (125) of the carriers' spouses agreed to genetic counseling and
      testing. Ten couples at risk for affected offspring were identified and offered
      prenatal genetic counseling and diagnosis. CONCLUSIONS: The genetic screening
      program, the first of its kind reported in a Druze community, was well received.
      We expect this program to increase awareness of genetic counseling, to contribute
      to disease prevention, and to serve as a model for other isolated communities.

PMID- 19092442
TI  - Patient interest in recording family histories of cancer via the Internet.
AB  - PURPOSE: This study investigated the interest of mammogram patients in using
      electronic tools for recording their family histories of cancer (FHC). METHODS:
      Semistructured interviews were conducted with 65 patients visiting a breast
      center at a referral hospital in Cleveland, Ohio. RESULTS: Most (n = 40; 62%)
      respondents expressed interest in using an electronic tool for recording FHC and
      associated its use with a range of benefits to themselves, their families, and
      their health care providers. Women who were not interested (n = 25; 38%) in using
      an electronic tool for recording FHC were concerned about privacy issues,
      computer proficiency, and giving up the opportunity to provide family history
      information directly to the health care provider. Interest in using an electronic
      tool for recording FHC was not significantly associated with age, race, level of
      education or income, personal or FHC, or Internet access and frequency of use.
      CONCLUSION: Electronic documentation of FHC was seen as largely desirable.
      However, clinical services to facilitate systematic family history documentation
      are likely to require more than one avenue for collecting and communicating this
      information, as not everyone who wants to provide a FHC to a health care provider
      is comfortable using the Internet to do so.

PMID- 19092444
TI  - The role of the F508C mutation in congenital bilateral absence of the vas
      deferens.
AB  - PURPOSE: Congenital bilateral absence of the vas deferens is a pathologic
      condition associated with normal spermatogenesis, azoospermia, and lack of both
      vasa deferentia. A significant association between mutations in the cystic
      fibrosis transmembrane conductance regulator gene among men with congenital
      bilateral absence of the vas deferens has been established. The objective of this
      study was to determine whether the F508C variant in the cystic fibrosis
      transmembrane conductance regulator gene has a significant effect on congenital
      bilateral absence of the vas deferens prevalence, when present in conjunction
      with a second cystic fibrosis transmembrane conductance regulator disease causing
      mutation. METHODS AND RESULTS: We compared the frequency of F508C in male
      subjects submitted for diagnostic testing on suspicion of cystic fibrosis or
      during cystic fibrosis carrier screening, to men with a clinical diagnosis of
      congenital bilateral absence of the vas deferens. Although frequencies of F508C
      did not vary significantly between 850 individuals undergoing cystic fibrosis
      carrier screening and those submitted for diagnostic testing on suspicion of
      cystic fibrosis, the frequency of F508C in the congenital bilateral absence of
      the vas deferens population was significantly higher than expected (chi2 = 6.95,
      corrected P = 0.0486). CONCLUSION: We conclude that the F508C variant in cystic
      fibrosis transmembrane conductance regulator may represent a pathogenic defect
      and lead to congenital bilateral absence of the vas deferens when combined with a
      second cystic fibrosis transmembrane conductance regulator mutation.

PMID- 19092446
TI  - Clinical genetics provider real-time workflow study.

PMID- 19092449
TI  - Insulin resistance is associated with advanced liver fibrosis and high body mass
      index in HIV/HCV-coinfected patients.

PMID- 19092448
TI  - Simultaneous initiation (coinitiation) of pharmacotherapy with triiodothyronine
      and a selective serotonin reuptake inhibitor for major depressive disorder: a
      quantitative synthesis of double-blind studies.
AB  - To examine the efficacy and overall tolerability of the simultaneous initiation
      of treatment (coinitiation) with triiodothyronine (T3) and a selective serotonin
      reuptake inhibitor (SSRI) for major depressive disorder (MDD). Sources of date
      were Medline/Pubmed, EMBASE, the Cochrane database, and program syllabi from
      major psychiatric meetings held since 1995. The study selection comprised double
      blind, randomized clinical trials comparing T3-SSRI coinitiation therapy versus
      SSRI monotherapy for MDD. Data were extracted with the use of a precoded form.
      Data from four clinical trials involving a total of 444 patients with MDD were
      identified and combined using a random effects model. There was no statistically
      significant difference in terms of remission rates or response rates at week 1,
      week 2, or at endpoint between the two treatment groups (SSRI+T3 coinitiation
      therapy vs. SSRI monotherapy). Pooled response and remission rates at endpoint
      for the SSRI+T3 versus SSRI monotherapy groups were 64.6 versus 58.5% and 46.8
      versus 44.8%, respectively. In addition, there was no statistically significant
      difference in overall rates of premature discontinuation of treatment, or in the
      rate of premature discontinuation of treatment owing to inefficacy or intolerance
      between the two treatment groups. Notwithstanding important methodological
      differences between the studies included in the meta-analysis in terms of patient
      characteristics and treatment protocols, these results do not support the notion
      that simultaneous initiation of treatment of MDD with an SSRI and T3 is more
      effective than SSRI monotherapy. However, given the etiologically diverse and
      clinically heterogeneous nature of MDD, it is at least plausible that T3-SSRIs
      coinitiation therapy may be effective for a particular subgroup of patients
      including patients with atypical depression or patients with a functional
      polymorphism of the D-1 deiodinase gene. Clearly, further work is needed to help
      determine whether there are specific MDD populations that can, indeed, benefit
      from T3-SSRI coinitiation therapy.

PMID- 19092450
TI  - Repeat hepatitis B vaccination may lead to seroprotection in HIV-infected
      patients who do not respond to an initial series.

PMID- 19092451
TI  - Thyroid dysfunction and relationship to antiretroviral therapy in HIV-positive
      individuals in the HAART era.

PMID- 19092452
TI  - HIV testing attitudes and practices among clinicians in the era of updated
      Centers for Disease Control and Prevention recommendations.

PMID- 19092453
TI  - Barriers to recruit female commercial sex workers for HIV vaccine trials: the Rio
      de Janeiro experience.

PMID- 19092454
TI  - Helicobacter pylori IgG antibodies in aqueous humor and serum of subjects with
      primary open angle and pseudo-exfoliation glaucoma in a South Indian population.
AB  - PURPOSE: A prospective, nonrandomized, comparative study was carried out to
      investigate levels of anti-Helicobacter pylori-specific IgG antibodies in the
      aqueous humor and serum of patients with primary open angle glaucoma (POAG),
      exfoliation syndrome [pseudo-exfoliation glaucoma (PXFG)], and with normotensive
      cataract patients, who served as controls. METHODS: Aqueous humor was aspirated
      at the beginning of glaucoma surgery from 50 eyes of 50 patients with POAG, with
      PXFG and at the beginning of phacoemulsification cataract surgery from controls.
      Serum samples were obtained. Anti-H. pylori IgG concentration in the aqueous
      humor and serum was measured by means of enzyme linked immunosorbent assay.
      RESULTS: Serum analysis of anti-H. pylori IgG antibodies revealed statistically
      significant difference between POAG and PXFG (52.26+/-52.51 vs. 25.22+/-35.27,
      P=0.01). Also, the difference between POAG and controls was statistically
      significant (54.05+/-55.04 vs. 33.83+/-41.73, P=0.04). However, on comparing PXFG
      with the control group, the difference was statistically insignificant (P=0.12).
      The mean concentration of anti-H. pylori IgG antibodies in aqueous humor of
      patients in POAG and controls were not statistically different (3.93+/-5.14 vs.
      2.65+/-2.87, respectively, P=0.73). The mean concentration of anti-H. pylori IgG
      antibodies in aqueous humor of patients in PXFG and controls were not
      statistically different (8.87+/-30.25 vs. 2.65+/-2.87, respectively, P=0.83).
      There was also no statistical difference of IgG levels between POAG and PXFG
      (3.93+/-5.14 vs. 8.87+/-30.25, respectively, P=0.87). CONCLUSIONS: The levels of
      anti-H. pylori IgG titers in sera of individuals with POAG were significantly
      higher compared with PXFG and control groups. We support the hypothesis of the
      role of anti-H. pylori antibodies in causative mechanism for POAG. We could not
      find a significant link between the anti-H. pylori IgG antibodies and the PXFG.

PMID- 19092455
TI  - Impact and permanence of LASIK-induced structural changes in the cornea on
      pneumotonometric measurements: contributions of flap cutting and stromal
      ablation.
AB  - PURPOSE: To determine the factors that lead to changes in intraocular pressure
      (IOP) measurements after laser-assisted in situ keratomileusis (LASIK) and their
      long-term stability. PATIENTS AND METHODS: Five hundred twenty-two myopic eyes
      and 296 hyperopic eyes were enrolled in the study. Pneumotonometry was used to
      measure IOP once in the preoperative stage and twice in the postoperative stage-1
      month after the operation and 1 year later. Ultrasonic pachymetry was used to
      determine preoperative and intraoperative corneal thicknesses and axial length of
      the eye, whereas optical pachymetry was used in the preoperative stage and 1
      month after surgery. Corneal topography was used to determine the preoperative
      and postoperative mean curvature of the anterior surface of the cornea over 3 and
      5-mm diameter regions. Comparative statistical analysis of the retrospective data
      series was performed. RESULTS: A highly significant reduction of IOP readings is
      found after LASIK for both myopic and hyperopic eyes. The reduction is stable 1
      year after LASIK. In the case of myopic eyes, the reduction has a highly
      significant linear correlation with the amount of tissue ablated in the central
      region of the cornea. CONCLUSIONS: Pneumotonometric IOP readings after LASIK are
      reduced, without recovering preoperative values even 1 year after surgery,
      because of flap cutting and tissue removal in the central region of the cornea.
      The contribution of flap cutting is estimated to be (1.6+/-0.8) mm Hg, whereas
      ablation contributes an additional (0.029+/-0.003) mm Hg/microm of removed
      tissue. This effect should be considered when evaluating the accuracy of IOP
      measurements in LASIK patients who are at risk for developing glaucoma.

PMID- 19092456
TI  - The influence of central corneal thickness and corneal curvature radius on the
      intraocular pressure as measured by different tonometers: noncontact and goldmann
      applanation tonometers.
AB  - PURPOSE: The aim of this study was to examine whether or not central corneal
      thickness (CCT) and corneal curvature radius (CCR) influence the concordance of
      intraocular pressure (IOP) readings taken with a noncontact tonometer (NCT) and a
      Goldmann applanation tonometer (GAT). METHODS: Eighty-seven eyes from 87 patients
      without any histories of intraocular operation were enrolled in the present
      study. We calculated the difference in IOP readings between the 2 methods (NCT
      GAT), and then examined the relationship between the IOP readings, and CCT and
      CCR using a linear regression line. RESULTS: IOP measured by both NCT (r=0.515,
      P<0.0001) and GAT (r=0.237, P<0.05) was significantly correlated with CCT. NCT
      readings were significantly higher in the thicker group (CCT>or=526.9 microm)
      than in the thinner group (CCT<526.9 microm) (P<0.005). GAT readings had no
      difference between the thicker and thinner groups. IOP measured by GAT (r=-0.261,
      P<0.05), but not that measured by NCT (r=-0.111, P=0.3042), showed a significant
      negative correlation with CCR. An IOP value of (NCT-GAT) had a significant
      positive correlation with not only CCT (r=0.666, P<0.0001) but also CCR (r=0.227,
      P<0.05). The value of (NCT-GAT) was significantly higher in the thicker group
      than in the thinner group (P<0.005). CONCLUSIONS: NCT can be more affected by CCT
      than GAT. CCR could influence the measurements of GAT, but not those by NCT. CCT
      and CCR can therefore influence the discordance of IOP readings taken with NCT
      and GAT.

PMID- 19092457
TI  - A comparison of catch trial methods used in standard automated perimetry in
      glaucoma patients.
AB  - PURPOSE: To compare the false-positive (FP) response rates between 2 methods used
      by the Humphrey Field Analyzer in glaucoma patients. METHODS: One eye of one
      hundred and twenty glaucoma patients was tested twice within 2 months with 24-2
      SITA Standard and 24-2 full threshold (FT) perimetric test procedures. FP rates
      were obtained with the response time window (RTW) method used by SITA and the
      blank presentation (BP) method of the size V FT procedure. False-negative (FN)
      catch trial rates were also examined. A repeated measure, 2 x 2 analysis of
      variance was used to examine error rates, and FP rates for visits 1 and 2 were
      regressed to investigate its relationship. RESULTS: For FP rates on the first 2
      visits, glaucoma patients had no significant differences comparing RTW (SITA)
      with BP (FT) (1.99% vs. 1.88%) and higher mean FN rates (4.11% vs. 1.69%,
      P=0.001); the FP rates at visit 2 were similar (1.69% vs. 2.08%) and FN rates
      were lower for both methods at visit 2. However, when comparing patients with FP
      responses that occurred with both RTW and BP methods, RTW rates were lower (3.58%
      vs. 7.72%, P=0.007). CONCLUSIONS: The RTW method seems to underestimate FP
      response rates.

PMID- 19092458
TI  - The impact of risk calculation on treatment recommendations made by glaucoma
      specialists in cases of ocular hypertension.
AB  - PURPOSE: To determine whether a risk calculator changes treatment recommendations
      made by glaucoma specialists in cases of ocular hypertension. METHODS: Two groups
      of case scenarios were created using the results of the Ocular Hypertension
      Treatment Study (OHTS) such that pairs of scenarios had the same risk of
      developing glaucoma. Glaucoma specialists were asked to review the cases and to
      make treatment recommendations. Only the second group included the estimated risk
      of glaucoma. The recommendations of the specialists were analyzed using ordinal
      regression and 2 measures termed confidence and inconsistency. The relative
      weighting of risk factors derived from physician recommendations was also
      compared with the weighting of those factors in the OHTS. The main outcome
      measure was quantitative change in recommendations when physicians were provided
      with an estimate of glaucoma risk. RESULTS: Inclusion of the calculator changed
      recommendations, increasing the measure of confidence and decreasing the measure
      of inconsistency. The relative weighting of risk factors by physicians in cases
      in which they did not have a risk calculation were different from the weights of
      those same risk factors in the OHTS. Even with the risk calculation, physicians
      tended to weight intraocular pressure and cup-disc ratio more heavily than the
      OHTS would suggest. CONCLUSIONS: Use of a risk calculator in cases of ocular
      hypertension changed treatment recommendations. Furthermore, the relative
      weighting of risk factors was more consistent with the published results from the
      OHTS when a risk calculation was available.

PMID- 19092459
TI  - Accuracy of scanning laser polarimetry, scanning laser tomography, and their
      combination in a glaucoma screening trial.
AB  - PURPOSE: To compare the usefulness in glaucoma screening of scanning laser
      polarimetry (GDx-VCC), scanning laser tomography [Heidelberg retina tomograph II
      (HRT II)], and their combined evaluation. METHODS: In a nonpopulation-based
      prepublicized trial, self-recruited white participants were screened for glaucoma
      with GDx-VCC, HRT II, and by independent clinical examination. Cases with
      possible glaucoma as found with any of the screening methods underwent a detailed
      clinical investigation to verify or exclude glaucoma. RESULTS: Of the 136
      attendees 118 participants (218 eyes) successfully underwent the GDx-VCC and HRT
      II measurements. Twenty-three eyes (11%) of 13 participants had glaucoma.
      Seventeen of these glaucomatous eyes (74%) had early damage. Evaluated
      separately, the GDx-VCC screening test (borderline cases grouped with the normal
      cases) performed best with 96.8% specificity, 89.5% accuracy, 7.5 positive
      likelihood ratio (PLR), but with only 23.8% sensitivity. Accuracy and PLR for all
      HRT parameters were <86.4% and <3.7, respectively. Combining different threshold
      criteria, for GDx-VCC accuracy increased to 90.3% to 90.8% and PLR to 14.0 to
      17.7; but for HRT no useful increase was seen (accuracy <86.4% and PLR<4.7 for
      all combinations). Combination of the best HRT and GDx-VCC criteria resulted in a
      PLR which was increased compared with the HRT combinations, but decreased
      compared with the GDx-VCC combinations (PLR<12.7 for all combinations).
      CONCLUSIONS: In this white screening population with relatively high risk for
      mild glaucomatous damage, a combination of different GDx-VCC criteria was useful
      for glaucoma screening; but combinations of HRT criteria or combinations of GDx
      VCC criteria with HRT criteria were less good for this purpose.

PMID- 19092460
TI  - Central corneal thickness and glaucoma in adult Chinese: the Beijing Eye Study.
AB  - PURPOSE: The aim of this study was to evaluate whether glaucoma was related to
      central corneal thickness (CCT). METHODS: The Beijing Eye Study 2006 is a
      population-based study that included 3251 (73.3%) subjects (aged 45+y) out of the
      4439 subjects who had participated in the survey in 2001, and who returned for a
      reexamination. The main outcome measures were central corneal thickness and
      presence and progression of glaucomatous optic neuropathy. RESULTS: Measurements
      of CCT were available for 3100 (95.4%) subjects. CCTs did not vary significantly
      (P>0.10) between the "optic disk glaucoma" [n=78 (2.5%) subjects; 551+/-32
      microm], the "perimetric glaucoma" [n=38 (1.1%) subjects; 550+/-31 microm], and
      the normal groups (n=3022; 556+/-33 microm). The CCT was not significantly
      associated with the neuroretinal rim area (P=0.28) or the mean visual-field
      defect (measured by frequency-doubling perimetry) (P=0.22). In multiple
      regression analysis, the CCT was significantly associated with male sex,
      (P<0.001), urban region (P<0.001), and intraocular pressure measurements
      (P<0.001); whereas it was not significantly (P=0.17) associated with chronic open
      angle glaucoma. During follow-ups from 2001 to 2006, 42 subjects, who showed a
      progression of, or development of glaucomatous abnormalities of the optic nerve
      head, did not differ significantly (P=0.30) in CCTs from the stable group.
      CONCLUSIONS: CCTs might not be markedly different between glaucomatous and normal
      eyes. The reasons for the discrepancies between the present population-based
      study and previous hospital-based investigations might be due to the differences
      in study design and mode of selection of study participants.

PMID- 19092461
TI  - Corneal endothelial cell loss after mitomycin C-augmented trabeculectomy.
AB  - PURPOSE: To determine the effect on the corneal endothelium of mitomycin C (MMC)
      augmented trabeculectomy 3 and 12 months after surgery. PATIENTS AND METHODS: In
      a prospective, observational clinical study, 14 eyes of 14 patients with well
      established open angle glaucoma were followed for 12 months after MMC-augmented
      trabeculectomy. We measured the endothelial cell density, the variation in mean
      cell size, the percentage of hexagonal cells, and the central corneal thickness
      at baseline and 3 and 12 months postoperatively. RESULTS: The mean endothelial
      cell density was 2525 [standard deviation (SD) 457] cells/mm(2) before surgery
      and 2332 (SD 643) cells/mm(2) and 2283 (SD 597) cells/mm(2) at 3 and 12 months
      after surgery, respectively, representing a cell loss of 9.5% (P=0.052) and 10.0%
      (P=0.027). The cell loss from 3 to 12 months was nonsignificant (P=0.40). After
      12 months of follow-up, the variation in mean cell size and the percentage of
      hexagonal cells had not yet stabilized around the preoperative values.
      CONCLUSIONS: Our results show that significant cell loss occurs during or
      immediately after MMC-augmented trabeculectomy. However, no progressive cell loss
      was observed from 3 to 12 months, demonstrating that MMC has no prolonged toxic
      effect on the corneal endothelium. From 3 to12 months after MMC-augmented
      trabeculectomy, active endothelial adaptations were taking place.

PMID- 19092462
TI  - Effect of local anesthesia on trabeculectomy success.
AB  - PURPOSE: To compare the long-term results of trabeculectomy surgery with
      subconjunctival anesthesia versus topical lidocaine 2% jelly. METHODS: A
      retrospective review of the long-term intraocular pressure (IOP) of 57
      trabeculectomies previously enrolled in a prospective study comparing
      subconjunctival anesthesia to topical lidocaine 2% jelly. Baseline data included
      patient demographics, diagnosis, and ophthalmic history. Postoperative data
      included IOP, glaucoma therapy, and any interventions. Follow-up was conducted by
      reviewing the medical charts from July 2002 to August 2007. Differences between
      the groups were statistically assessed by the Student t test, chi(2) test, Fisher
      exact test, and Kaplan-Meier survival analysis. RESULTS: Data were available for
      57 of the 58 original study patients, with a median age of 65 years. The median
      follow-up time was 4.2 years for both groups (range: 0.1 to 4.8). There were no
      statistically significant differences in baseline characteristics and follow-up
      observations. At the 4-year follow-up, 29.5% of the subconjunctival anesthesia
      patients versus 39.5% of the topical lidocaine 2% jelly patients were complete
      success (IOP between 6 to 21 mm Hg and 20% reduction without glaucoma therapy or
      repeat filtration surgery, P=0.15) and 82.7% of the subconjunctival anesthesia
      patients versus 95.8% for the topical lidocaine 2% jelly patients were qualified
      success (above with or without glaucoma therapy, P=0.39). CONCLUSIONS: Though
      small numbers observed, the 2 anesthetic techniques did not seem to influence the
      long-term success of trabeculectomy surgery. Further studies with more patients
      are warranted.

PMID- 19092463
TI  - Long-term effects of latanoprost monotherapy on intraocular pressure in Japanese
      glaucoma patients.
AB  - PURPOSE: To assess the long-term effects of latanoprost monotherapy on
      intraocular pressure (IOP) reduction in Japanese patients with glaucoma. METHODS:
      Those enrolled were patients with glaucoma who had been treated on an outpatient
      basis for more than 5 years at the Glaucoma Outpatient Clinic of the University
      of Yamanashi Hospital, with only latanoprost ophthalmic solution as the first
      drug of choice. Subjects who underwent treatment with a drug other than
      latanoprost, laser therapy, or surgery were eliminated from the study, and IOP
      reduction by latanoprost, the dropout rate and causative reasons, and the types
      of additional therapy were assessed in a retrospective manner. RESULTS: Seventy
      two patients (age: 68.3+/-13.0 y) were enrolled, including 40 men and 32 women
      for the checking of 72 eyes. There were 47 eyes with normal tension glaucoma
      (NTG) and 25 with primary open angle glaucoma (POAG). The mean duration of
      latanoprost monotherapy was 4.1+/-2.0 years (range: 5 mo to 7 y, median: 4.0 y).
      IOP reduction rates (cumulative dropout rates) relative to the mean IOP before
      the start of latanoprost monotherapy (17.8+/-3.4 mm Hg) were 11.5% (8.3%), 15.5%
      (8.3%), 13.0% (9.7%), 13.4% (13.9%), 13.5% (19.4%), and 10.6% (30.6%) at 6
      months, 1 year, 2 years, 3 years, 4 years, and 5 years after the start of
      monotherapy, respectively. Although latanoprost demonstrated significant IOP
      reduction in POAG and NTG, eyes with POAG showed significant IOP reduction than
      those with NTG. Two eyes presented with local adverse events resulting from the
      discontinuation of use of latanoprost, and 4 eyes required filtering surgery.
      CONCLUSIONS: Latanoprost stably reduced IOP over a long term and maintained
      visual field in approximately 70% of eyes with glaucoma after treatment for 5
      years.

PMID- 19092464
TI  - Efficacy and tolerability of prostaglandin analogs: a meta-analysis of randomized
      controlled clinical trials.
AB  - AIM: This systematic meta-analysis was performed to evaluate the intraocular
      pressure (IOP) lowering effects and tolerability of latanoprost, bimatoprost, and
      travoprost. METHODS: Clinical trials published up to July 2006 were thoroughly
      searched using all available databases and resources. The inclusion criteria were
      prospective randomized controlled clinical trials; patients with primary open
      angle glaucoma or ocular hypertension; and prostaglandin monotherapy, without
      systemic/ocular medications or laser/surgery that could affect IOP within the
      past 3 months. Study quality was assessed with the Jadad scoring system, and
      potential bias was eliminated by robust statistical and independent reviews of
      publications. The main outcome measures were efficacy assessed by IOP (taken at 8
      AM, noon, 4 PM, and 8 PM) change at 3 months from baseline and tolerability
      assessed by the incidence of conjunctival hyperemia. RESULTS: Eight trials were
      identified (n=1610 patients). IOP change from baseline was statistically
      significantly greatest with bimatoprost, compared with latanoprost at all time
      points [weighted mean (WM) 8 AM: WM=0.50 mm Hg; P=0.05; 95% confidence intervals
      (CIs) 0.01-0.99; noon: WM=1.17 mm Hg; P<0.001; 95% CI 0.68-1.66; 4 PM: WM=0.78 mm
      Hg; P=0.003; 95% CI 0.26-1.29; 8 PM: WM=0.67 mm Hg; P=0.04; 95% CI 0.02-1.32],
      and with travoprost during the daytime (8 AM: WM=1.02 mm Hg; P=0.004; 95% CI 0.32
      1.72; noon: WM=0.86 mm Hg; P=0.02; 95% CI 0.12-1.59). Latanoprost and travoprost
      were comparable in their ability to reduce IOP at all time points (P<or=0.82).
      The incidence of hyperemia was less with latanoprost and travoprost [latanoprost
      vs. bimatoprost: relative risk=0.59; P<0.001; 95% CI 0.50-0.69; travoprost vs.
      bimatoprost: relative risk=0.84; P=0.05; 95% CI 0.70-1.00]. CONCLUSIONS: The
      findings suggest a greater efficacy of bimatoprost compared with latanoprost and
      travoprost, although the incidence of hyperemia was lower with the latter 2
      agents.

PMID- 19092465
TI  - An eight-week, multicentric, randomized, interventional, open-label, phase 4,
      parallel comparison of the efficacy and tolerability of the fixed combination of
      timolol maleate 0.5%/brimonidine tartrate 0.2% versus fixed combination of
      timolol maleate 0.5%/dorzolamide 2% in patients with elevated intraocular
      pressure.
AB  - PURPOSE: To compare the efficacy and tolerability of the fixed combination of
      timolol maleate 0.5%/brimonidine tartrate 0.2% versus fixed combination of
      timolol maleate 0.5%/dorzolamide 2% in patients with elevated intraocular
      pressure (IOP) over 8 weeks. PATIENTS AND METHODS: This 8-week, multicentric,
      interventional, randomized, open-label, parallel group study was conducted at 4
      centers in Brazil and 1 center in Argentina. Patients with open-angle glaucoma or
      ocular hypertension were randomized to receive bilaterally fixed combination of
      brimonidine/timolol maleate 0.5% or fixed combination of dorzolamide 2%/timolol
      0.5% twice daily at 8:00 AM and 8:00 PM. A modified diurnal tension curve (8:00
      AM, 10:30 AM, 02:00 PM, and 4:00 PM) followed by the water drinking test (WDT),
      which estimates IOP peak of diurnal tension curve, were performed in the baseline
      and week-8 visits. Adverse events data were recorded at each visit. RESULTS: A
      total of 210 patients were randomized (brimonidine/timolol, n=111;
      dorzolamide/timolol, n=99). Mean baseline IOP was 23.43+/-3.22 mm Hg and 23.43+/
      4.06 mm Hg in the patients treated with brimonidine/timolol and
      dorzolamide/timolol, respectively (P=0.993). Mean diurnal IOP reduction after 8
      weeks were 7.02+/-3.06 mm Hg and 6.91+/-3.67 mm Hg, respectively (P=0.811). The
      adjusted difference between groups (analysis of covariance) at week 8 was not
      statistically significant (P=0.847). Mean baseline WDT peak was 27.79+/-4.29 mm
      Hg in the brimonidine/timolol group and 27.68+/-5.46 mm Hg in the
      dorzolamide/timolol group. After 8 weeks of treatment, mean WDT peaks were
      20.94+/-3.76 mm Hg (P<0.001) and 20.98+/-4.19 (P<0.001), respectively. The
      adjusted difference between groups (analysis of covariance) was not statistically
      significant (P=0.469). No statistical difference in terms of adverse events was
      found between groups. CONCLUSIONS: Both fixed combinations were capable of
      significantly reducing the mean diurnal IOP, mean diurnal peak, and mean WDT peak
      after 8 weeks of treatment. Also, both fixed combinations are well tolerated with
      few side effects.

PMID- 19092466
TI  - Ten years follow-up after deep sclerectomy with collagen implant.
AB  - PURPOSE: To evaluate the long-term success rate and complications of
      nonpenetrating deep sclerectomy with collagen implant in open-angle glaucoma.
      PATIENTS AND METHODS: Clinical, prospective, monocentric, nonrandomized, unmasked
      study on 105 patients with medically uncontrolled glaucoma. A standard procedure
      deep sclerectomy with collagen implant was performed. Complete examinations were
      performed before surgery and postoperatively at 1 and 7 days; 1, 2, 3, 6, 9, and
      12 months and then every 6 months during the 10 following years. RESULTS: The
      mean follow-up was 101.5+/-43.1 (3 to 144) months [mean+/-SD, (range)]. The
      preoperative intraocular pressure (IOP) was 26.8+/-7.7 (14 to 52) mm Hg and the
      best-corrected visual acuity 0.71+/-0.33 (0.02 to 1.5). Ten years after surgery
      IOP was 12.2+/-4.7 (6 to 20) mm Hg and best-corrected visual acuity 0.63+/-0.34
      (0.01 to 1.2) (number of remaining patients=52). The mean number of medications
      per patient went from 2.3+/-0.7 (1 to 4) down to 1.3+/-1.1 (0 to 3). An IOP
      <or=21 mm Hg without medication was achieved in 47.7% patients and in 89% with or
      without treatment. One major complication was reported. Goniopuncture was
      performed in 61 eyes (59.8%), 5-fluorouracil treatment given to 25 patients
      postoperatively and included needling (n=5). CONCLUSIONS: On the basis of a 10
      year follow-up deep sclerectomy with collagen implant demonstrated its efficacy
      in controlling IOP with few postoperative complications.

PMID- 19092467
TI  - Ex-PRESS glaucoma shunt dislocation into the anterior chamber.
AB  - We report a case of an 84-year-old man who had an Ex-PRESS R-50 glaucoma shunt
      placed under a scleral flap in his right eye for primary open angle glaucoma and
      uncontrolled intraocular pressure. Twenty-one days after placing the implant, the
      patient returned with a dislocated shunt resting in the inferior angle of the
      anterior chamber. Corrected vision was 20/30 with an intraocular pressure of 13
      mm Hg. There was no anterior chamber inflammation and no evidence of corneal
      decompensation. To our knowledge, this is the first report of an Ex-PRESS shunt
      dislocation into the anterior chamber. Ophthalmologists implanting this device
      should be aware of this possible complication of Ex-PRESS shunt insertion.

PMID- 19092468
TI  - Physician beliefs and behaviors related to glaucoma treatment adherence: the
      Glaucoma Adherence and Persistency Study.
AB  - PURPOSE: Patient adherence with topical glaucoma therapy is recognized as
      suboptimal. Though some studies have associated physician/patient interaction
      with adherence, little systematic research has explored the ophthalmologist's
      perspective of this interaction. Telephone interviews with physicians treating
      glaucoma were conducted to ascertain the extent to which multivariate analysis of
      physician demographics, beliefs, and behaviors could reveal differences
      potentially relevant to future adherence with topical glaucoma therapy for
      primary open-angle glaucoma, in conjunction with other phases of the Glaucoma
      Adherence and Persistency Study (GAPS). METHODS: Structured interviews were
      conducted with 103 ophthalmologists treating significant numbers of primary open
      angle glaucoma patients in a national managed care network. To the maximum extent
      possible, eligible patients of physicians interviewed were included in the other
      GAPS phases (claims analysis, patient surveys, and medical chart reviews).
      RESULTS: Physicians reported a wide range of beliefs and behaviors regarding
      patients' medication adherence, but beliefs and behaviors were linked. The
      segmentation analysis yielded 3 clusters of physicians, which we have described
      on the basis of their predominant beliefs as "reactives," "skeptics," and
      "idealists." The "idealists," though the smallest group, more often reported
      beliefs and behaviors that may be more positively associated with patient
      adherence, especially in the context of other GAPS findings. CONCLUSIONS:
      Physician vigilance for opportunities to detect and address nonadherence is
      suggested, as is interventional research on the basis of the constructs
      identified.

PMID- 19092469
TI  - Asymmetric progressive glaucomatous optic neuropathy in a patient with a rare
      developmental variant of the ophthalmic artery.
AB  - PURPOSE: To report a case of a developmental anatomic finding of the ophthalmic
      artery (OA) in a patient with ipsilateral progressive advanced glaucomatous optic
      neuropathy and visual field loss. METHODS: A 59-year-old Asian man with normal
      tension glaucoma had progressive asymmetric visual field loss OD. Magnetic
      resonance imaging and angiography of the orbit were performed because of
      continued progression despite medical and surgical intervention. RESULTS:
      Magnetic resonance angiography revealed an anomalous OA, lateral to the carotid
      artery and emanating from a branch of the middle meningeal artery. CONCLUSION: OA
      anomalies should be added to the differential diagnosis of risk factors for
      unilateral progressive glaucomatous optic neuropathy, and neuroradiologic imaging
      should be considered to detect such anatomic variants.

PMID- 19092470
TI  - Response to Healey and Mitchell in January/February 2008 issue of the Journal of
      Glaucoma.

PMID- 19092471
TI  - Nurses' role in patient safety.

PMID- 19092472
TI  - Engaging nurses in governing hospitals and health systems.

PMID- 19092473
TI  - Implementation of an evidence-based bladder scanner protocol.

PMID- 19092474
TI  - Rapid improvement event: an alternative approach to improving care delivery and
      the patient experience.
AB  - The most common quality improvement methodologies used in healthcare involve
      repetitive testing of ideas for rapid-cycle quality improvement. They typically
      take place over weeks or months, as identification of problems and root causes
      and tests of change occur. The authors describe an alternative approach to care
      delivery redesign, which reduces the time frame of problem identification and
      implementation of tests of change from weeks or months to days.

PMID- 19092476
TI  - Using rapid assessment to evaluate noise on an in-patient unit.
AB  - Rapid assessment was used to evaluate a noise problem on a busy, high-traffic,
      high-acuity medical/surgical telemetry unit over a 4-week period. Six sources of
      environmental noise were identified including conversational noise, noise from
      doors, noise from housekeeping activities, noise from the pneumatic message tube
      station, hallway noise, and miscellaneous noise. Our study also demonstrates the
      value of rapid-assessment methodology for the evaluation of clinical problems
      such as noise.

PMID- 19092477
TI  - Reducing serious injury from falls in two veterans' hospital medical-surgical
      units.
AB  - A large veteran's hospital participated in a year-long collaborative project
      across 9 hospitals to reduce serious injury from falls in acute care, targeting
      medical-surgical units. The primary objective of this project was to develop and
      test a set of interventions (bundles) to prevent serious physical injury
      (fractures and hemorrhagic bleeds) from patient falls. The interventions were
      implemented using tests of change on 2 medical-surgical units focused on engaging
      unit-based staff and combining innovations for vulnerable populations at greatest
      risk for injury if they fall.

PMID- 19092478
TI  - Perspectives of recently discharged patients on hospital fall-prevention
      programs.
AB  - The aim of this exploratory study was to understand the opinions and observations
      of recently discharged senior patients concerning the fall-prevention education
      received during their most recent hospitalization. The focus was on the extrinsic
      risk factors for falls. This project was conducted in a Michigan home care
      agency. Participants had to be Medicare home care patients, discharged from the
      affiliated hospital within 30 days, 65 years or older, and alert. Practical
      implications that might lead to fewer falls in the future as the goal of this
      research are discussed.

PMID- 19092479
TI  - Designing a postepidural fall risk assessment score for the obstetric patient.
AB  - The effects of an epidural combined with the need for early ambulation in the
      postpartum patient create a high risk for falls. We developed a standardized
      assessment score, based on 8 areas of assessment, to evaluate the fall risk of a
      postepidural patient. This score was developed using 2 other assessment tools, as
      well as considering the unique issues associated with the post-epidural patient.
      The scoring system is user-friendly and applicable to the labor and delivery
      setting.

PMID- 19092480
TI  - Workplace empowerment and magnet hospital characteristics as predictors of
      patient safety climate.
AB  - This study tested a theoretical model derived from Kanter's theory of workplace
      empowerment by surveying a random sample of 300 registered nurses employed in
      acute care hospitals across the Canadian province of Ontario. The results of this
      study effectively replicated the findings of a previous exploratory study.
      Specific nursing practice environment characteristics that positively influence
      the climate of patient safety were identified. This study provides nurse leaders
      with ideas for improving the patient safety climate by improving the quality of
      nurses' work environments.

PMID- 19092481
TI  - Perception of safety culture by nurses in hospitals in china.
AB  - The safety culture in hospitals in China was investigated using a self-designed
      questionnaire. A convenience sample of 217 registered nurses responded positively
      in the areas of the safety of shift change processes, hospital and nursing
      leadership attention to patient safety, and staff cooperation, among others.
      However, a punitive safety culture was identified, and registered nurses reported
      a lack of safety committees, fear of reporting errors, punishment of the person
      making an error, and underreporting of nursing errors.

PMID- 19092482
TI  - Call bell requests, call bell response time, and patient satisfaction.
AB  - Based in the center of nursing activity, the nurse call system has potential to
      gather basic data such as the number of calls and the response time. Analyzing
      this information may shed light on performance and patient satisfaction. This
      study used a correlational design to examine results from a patient satisfaction
      survey administered at discharge in relation to the number of call bell requests
      from the patient's room and call bell response time.

PMID- 19092483
TI  - Improving patient safety: patient-focused, high-reliability team training.
AB  - Healthcare systems are recognizing "human factor" flaws that result in adverse
      outcomes. Nurses work around system failures, although increasing healthcare
      complexity makes this harder to do without risk of error. Aviation and military
      organizations achieve ultrasafe outcomes through high-reliability practice. We
      describe how reliability principles were used to teach nurses to improve patient
      safety at the front line of care. Outcomes include safety-oriented, teamwork
      communication competency; reflections on safety culture and clinical leadership
      are discussed.

PMID- 19092484
TI  - A collaborative model to introduce quality and safety content into the
      undergraduate nursing leadership curriculum.
AB  - Today's nursing students need an understanding of quality and safety (Q/S)
      concepts as well as the nurse's role in all phases of Q/S activities. Nursing
      students' Q/S learning experiences are typically anecdotal. This article
      describes a practice-academic partnership that raised students' awareness of Q/S
      within the practice environment. This partnership also resulted in healthcare
      providers' increased commitment to a culture of safety.

PMID- 19092485
TI  - Canada, chrysotile and cancer: Health Canada's Asbestos International Expert
      Panel report.

PMID- 19092486
TI  - Health care and social issues of immigrant rescue and recovery workers at the
      World Trade Center site.
AB  - This article reviews the experience of a unique occupational group of World Trade
      Center (WTC) workers: immigrant workers. This group is comprised largely of men,
      laborers, who are first-generation immigrants. The majority of these workers are
      from Latin America (predominantly from Ecuador and Colombia) or from Eastern
      Europe (predominantly from Poland). Our data shows that the disease profile
      observed in these workers was what we have previously reported for WTC working
      population as a whole. Recent reports have begun to document the disproportionate
      burden of occupational hazards, injuries, and illnesses experienced by immigrant
      workers in the United States. The WTC experience of immigrants exemplified this
      burden but, additionally, highlighted that this burden is exacerbated by
      limitations in access to appropriate health care, disability and compensation
      benefits, and vocational rehabilitation services. A clinical program that was
      designed to address the complex medical and psychosocial needs of these workers
      in a comprehensive manner was successfully established. Full justice for these
      workers depends on larger societal changes.

PMID- 19092487
TI  - DDT exposure, work in agriculture, and time to pregnancy among farmworkers in
      California.
AB  - OBJECTIVE: This study examined whether exposure to pesticides, including
      dichlorodiphenyltrichloroethane (DDT), was associated with longer time to
      pregnancy (TTP). METHODS: Pregnant women (N = 402) living in a migrant farmworker
      community were asked how many months they took to conceive. Women reported their
      and their partners' occupational and home pesticide exposure preceding
      conception. In a subset (N = 289), levels of DDT and
      dichlorodiphenyldichloroethylene (DDE), were measured in maternal serum. RESULTS:
      No associations were seen with p, p'-DDT, o, p'-DDT, or p, p'-DDE. Maternal
      occupational pesticide exposure (fecundability odds ratios [fOR] = 0.8, 95% CI:
      0.6 to 1.0), home pesticide use (fOR = 0.6, 95% CI: 0.4 to 0.9), and residence
      within 200 ft of an agricultural field (fOR = 0.7, 95% CI: 0.5 to 1.0) were
      associated with reduced fecundability (ie, longer TTP). CONCLUSIONS: Longer TTP
      was seen among women, but not men, reporting exposure to agricultural and home
      pesticides.

PMID- 19092489
TI  - Reflux symptoms and disorders and pulmonary disease in former World Trade Center
      rescue and recovery workers and volunteers.
AB  - BACKGROUND: Gastroesophageal reflux disease is one of the most prevalent
      conditions among former World Trade Center (WTC) rescue and recovery workers. The
      reason for this proposed association with an inhalation injury is unclear. In
      this study, we clinically characterized the reflux disorders in former WTC
      workers, and we investigated their association with pulmonary function
      abnormalities and with clinical diagnoses of other WTC-related diseases. METHODS:
      Forty-two former WTC workers underwent the following testing: symptom
      inventories, physical examination, spirometry, esophagogastroduodenoscopy, and 24
      hour pH monitoring studies for the evaluation of chronic reflux-like symptoms.
      Patients were classified into two groups based on clinical evaluation: group 1
      (reflux patients) including definitive reflux disorders (gastroesophageal reflux,
      nonerosive reflux, nonacid reflux, and laryngopharyngeal reflux diseases) and
      group 2 (no-reflux patients) patients without clinically significant reflux
      disease, including functional heartburn, and hypersensitive esophagus disorder.
      RESULTS: The reflux and no-reflux patients had significantly different Johnson
      DeMeester scores and esophageal acid exposure times. Patients with reflux
      disorders were more likely to have reduced forced vital capacity (chi2 = 5.49, P
      = 0.031) and also more likely to have been diagnosed with a lower airway disease
      (chi2 = 7.14, P = 0.008). We found no significant association between reflux and
      psychiatric disorders (chi2 = 0.02, P = 0.89), levels of exposure at the WTC
      site, or incidence of dry cough, or other upper airway disorders. CONCLUSIONS: A
      spectrum of reflux symptoms and disorders are present in WTC responders. Our data
      suggest that the presence of reflux disease is related to that of pulmonary
      function abnormality suggestive of air trapping and a diagnosis of a lower
      respiratory disease.

PMID- 19092488
TI  - Cumulative sensitization and disease in a beryllium oxide ceramics worker cohort.
AB  - OBJECTIVE: We followed a cohort of 136 beryllium oxide ceramics workers from 1992
      to 2003, including those who left employment, for beryllium sensitization and
      chronic beryllium disease (CBD). METHODS: We invited the cohort's participation
      in current worker surveys in 1992, 1998, 2000, and 2002-2003, and in former
      worker surveys in 2000-2001 and 2003. We calculated 11-year cumulative incidences
      (after 1992 initial survey) of sensitization and CBD, both crude and corrected
      for interval censoring; and period prevalences (including 1992 findings), crude
      and corrected. RESULTS: In 1992, point prevalences were 6% sensitized and 4% CBD.
      We obtained follow-up on 83% of 128 not sensitized in 1992. Crude cumulative
      incidences for sensitization and CBD were 13% and 9%, respectively; corrected
      were 15% and 11%. Crude period prevalences for sensitization and CBD were 16% and
      11%, respectively; corrected were 20% and 14%. Corrected period prevalences for
      pre-1992 machining work were 30% and 20%. CONCLUSIONS: With repeated testing over
      11 years, total sensitization and CBD in this cohort were triple initial 1992
      survey results.

PMID- 19092490
TI  - Risk factors for carpal tunnel syndrome and median neuropathy in a working
      population.
AB  - OBJECTIVE: To assess whether work-related physical activities are associated with
      Carpal tunnel syndrome (CTS), even when controlling for personal risk factors.
      METHODS: A cross-sectional assessment of 1108 workers from eight employers and
      three unions completed nerve conduction testing, physical examination, and
      questionnaires. CTS was defined by median neuropathy and associated symptoms.
      RESULTS: Eighteen workers had CTS and 131 had evidence of median neuropathy. CTS
      was highest among construction workers (3.0%) compared to other subjects (<1%).
      Logistic regression models for median neuropathy both personal and work-related
      risk factors. Work-related exposures were estimated by two methods: self-report
      and job title based ratings. CONCLUSIONS: Both work and personal factors mediated
      median nerve impairment. Construction workers are at an increased risk of CTS so
      awareness should be raised and interventions should specifically target this risk
      group.

PMID- 19092491
TI  - A study of the effectiveness of a workplace violence intervention for small
      retail and service establishments.
AB  - OBJECTIVE: Examine the effectiveness of a robbery and violence prevention program
      in small businesses in Los Angeles. METHODS: Gas/convenience, liquor and grocery
      stores, bars/restaurants, and motels were enrolled between 1997 and 2000.
      Intervention businesses (n = 305) were provided training, program implementation
      materials, and recommendations for a comprehensive security program. Control
      businesses (n = 96) received neither training nor program materials. RESULTS:
      Rate ratios comparing intervention to control businesses were 0.90 for violent
      crime (95% confidence limits [CL] = 0.53, 1.53) and 0.81 for robbery (95% CL =
      0.38, 1.73). The reduction in violent crime was concentrated in high-compliance
      intervention businesses (risk ratio = 0.74, 95% CL = 0.40, 1.36). Low-compliance
      intervention businesses had practically the same postintervention crime as the
      control businesses. CONCLUSIONS: Our results suggest that the workplace violence
      intervention may reduce violent crime among high-risk businesses, especially
      those with high program compliance.

PMID- 19092492
TI  - Infertility and spontaneous abortion among female hairdressers: the Hordaland
      Health Study.
AB  - OBJECTIVES: The authors investigated the risks of negative reproductive outcome
      among female hairdressers. METHODS: A cross-sectional study was conducted in 1997
      1999, and 16,907 women in their forties were invited (response 71%). Information
      on infertility, delayed conception, spontaneous abortions, smoking, education,
      and occupation was collected. RESULTS: Infertility and spontaneous abortion were
      higher among female hairdressers than among women in other occupations (adjusted
      relative risks = 1.30; 95% confidence intervals = 1.08 to 1.55 and 1.31; 1.07 to
      1.60, respectively). There was a significant interaction between work and smoking
      habits. Smoking increased the risk of infertility among women in other
      occupations, but this was not found among hairdressers. CONCLUSIONS: Female
      hairdressers have an increased risk of infertility and spontaneous abortions that
      might be due to their occupational chemical exposure. The risk was primarily
      found among never smokers.

PMID- 19092493
TI  - The role of tailored consultation following health-risk appraisals in employees'
      health behavior.
AB  - OBJECTIVES: This study evaluates employees' health and lifestyle changes
      following health risk appraisal only and health risk appraisal with a
      consultation (HRAC) based on the constructs of Transtheoretical model (TTM).
      METHODS: Sixty employees self-selected to an HRAC or health risk appraisal only,
      implemented in 6-month interval. Demographics, lifestyle behavior, and stage of
      change (SOC) assessments based on TTM along with weight, height, body mass index,
      blood pressure, blood glucose, and cholesterol were measured. RESULTS: Second
      health risk appraisal showed improvements in nutrition, fitness, and overall
      health in both groups (P < 0.05). Significant improvements were found between
      HRAC group and their SOC for exercise, nutrition, and overall lifestyle. Also,
      group differences in SOC for exercise, amount of snack food, fruits and
      vegetables consumed, and physical activity (P < 0.05) were significant.
      CONCLUSION: HRAC based on TTM constructs is effective in promoting behavior
      change in high-risk employees.

PMID- 19092494
TI  - The association of insulin medication possession ratio, use of insulin glargine,
      and health benefit costs in employees and spouses with type 2 diabetes.
AB  - OBJECTIVE: Measure the impact of insulin utilization on health costs and
      absenteeism. Compare outcomes between users of insulin glargine and other
      insulin. METHODS: Using a large retrospective database, this regression analysis
      examined annual health costs and absenteeism among employees and spouses with
      type 2 diabetes who used insulin. The analysis studied impacts of medication
      possession ratio (MPR) and glargine use, controlling for demographic factors,
      salary, and prior health care. RESULTS: Higher MPR was associated with
      significantly lower health costs for patients with high prior costs. Glargine
      users' MPR was higher than other insulin users' MPR (66% vs 54%, P < 0.0001).
      Among all insulin users, those using glargine had significantly lower total
      ($6771 vs $7969, P = 0.0046) and circulatory-specific ($312 vs $636, P < 0.0001)
      costs. CONCLUSIONS: Insulin MPR and the use of insulin glargine were associated
      with lower health care costs.

PMID- 19092495
TI  - Effects of grain dust on lungs prior to and following dust remediation.
AB  - OBJECTIVE: To determine longitudinal estimates of pulmonary function decline in
      Canadian grain elevator workers before and after dust control by analyzing data
      collected from five regions of Canada over 15 years. METHODS: Declines in forced
      expired volume in one second and forced vital capacity before and after dust
      control were estimated by using a generalized estimating equations approach.
      RESULTS: For grain workers who were in the grain industry for 20 or more years
      both before and after dust control: the mean annual loss of forced expired volume
      in one second was greatest among current smoking grain workers followed by ex
      smokers and nonsmokers, respectively. Similar results were obtained for forced
      vital capacity. CONCLUSIONS: Grain dust control was effective in reducing decline
      in the lung function measurements among grain workers in all smoking and exposure
      categories.

PMID- 19092496
TI  - Examining associations between job characteristics and health: linking data from
      the Occupational Information Network (O*NET) to two U.S. national health surveys.
AB  - OBJECTIVE: To determine whether the Occupational Information Network (O*NET)
      database can be used to identify job dimensions to serve as proxy measures for
      psychosocial factors and select environmental factors, and to determine whether
      these factors could be linked to national health surveys to examine associations
      with health risk behaviors and outcomes. METHODS: Job characteristics were
      obtained from O*NET 98. Health outcomes were obtained from two national surveys.
      Data were linked using Bureau of Census codes. Multiple logistic regression was
      used to examine associations between O*NET factors and cardiovascular disease,
      depression, and health risk factors. RESULTS: Seven of nine work organization or
      psychosocial factors were significantly associated with health risk behaviors in
      both the National Health and Nutrition Examination Survey III and National Health
      Interview Survey. CONCLUSIONS: This study demonstrates a method for linking
      independently obtained health and job characteristic data based on occupational
      code.

PMID- 19092497
TI  - Accuracy of self-reported smoking and secondhand smoke exposure in the US
      workforce: the National Health and Nutrition Examination Surveys.
AB  - OBJECTIVES: Occupational health studies often rely on self-reported secondhand
      smoke (SHS) exposure. This study examines the accuracy of self-reported tobacco
      use and SHS exposure. METHODS: Data on serum cotinine, self-reported tobacco use,
      and SHS exposure for US workers were extracted from three National Health and
      Nutrition Examination Surveys (n = 17,011). Serum cotinine levels were used to
      classify workers into SHS exposure categories. The percent agreement between self
      reported tobacco use and SHS exposure with the cotinine categories was
      calculated. RESULTS: Workers reporting tobacco use were 88% accurate whereas
      workers reporting work, home, or home+work exposures were 87% to 92% accurate.
      Workers reporting no SHS exposure were only 28% accurate. CONCLUSIONS: Workers
      accurately reported their smoking status and workplace-home SHS exposures, but
      substantial numbers reporting "no exposures" had detectable levels of cotinine in
      their blood, indicating exposure to SHS.

PMID- 19092498
TI  - Effect of chronic low level manganese exposure on postural balance: a pilot study
      of residents in southern Ohio.
AB  - OBJECTIVE: The objective of this study was to determine the effect of non
      occupational exposure to manganese (Mn) on postural balance. METHODS: Residents
      living near a ferromanganese refinery provided hair and blood samples after
      postural balance testing. The relationship between hair Mn and postural balance
      was analyzed with logistic regression. Following covariate adjustment, postural
      balance was compared with control data by analysis of covariance. RESULTS: Mean
      hair Mn was 4.4 microg/g. A significantly positive association was found between
      hair Mn and sway area (eyes open on the platform, P = 0.05; eyes closed on the
      platform, P = 0.04) and sway length (eyes open on the platform, P = 0.05; eyes
      closed on the platform, P = 0.04). Postural balance of residents was
      significantly larger than controls in 5 out of 8 postural balance outcomes.
      CONCLUSION: Preliminary findings suggest subclinical impairment in postural
      balance among residents chronically exposed to ambient Mn. A prospective study
      with a larger sample size is warranted.

PMID- 19092499
TI  - Safety factors predictive of job satisfaction and job retention among home
      healthcare aides.
AB  - OBJECTIVES: Although many of the well known work characteristics associated with
      job satisfaction in home health care have been documented, a unique aspect of the
      home health care aides' (HHA) work environment that might also affect job
      satisfaction is the fact that their workplace is a household. To obtain a better
      understanding of the potential impact of the risks/exposures/hazards within the
      household environment on job satisfaction and job retention in home care, we
      recently conducted a risk assessment study. METHODS: Survey data from a
      convenience sample of 823 New York City HHAs were obtained and analyzed. RESULTS:
      Household/job-related risks, environmental exposures, transportation issues,
      threats/verbal and physical abuse, and potential for violence were significantly
      correlated with HHA job satisfaction and job retention. CONCLUSIONS: Addressing
      the modifiable risk factors in the home health care household may improve job
      satisfaction and reduce job turnover in this work population.

PMID- 19092501
TI  - Lessons learned from the military.

PMID- 19092502
TI  - The relationship between combat casualty care and the advancement of trauma
      nursing.

PMID- 19092503
TI  - Toward the development of a worldwide military trauma system: an alliance between
      military nursing and the Society of Trauma Nurses.

PMID- 19092505
TI  - Nurses' role in the Joint Theater Trauma System.
AB  - Nurses' role within the Joint Theater Trauma System's trauma performance
      improvement program spans the entire trauma continuum. Nurses serve as trauma
      nurse coordinators at combat zone medical treatment facilities, flight nurses
      within the US Air Force Aeromedical Evacuation system, multidisciplinary trauma
      teams at overseas and stateside military and Veterans Affairs healthcare
      organizations, and members on trauma video teleconferences. Many of the trauma
      performance improvement initiatives that have occurred since the Joint Theater
      Trauma System inception have been led by nurses serving within the trauma
      continuum and resulted in successful outcomes for patients with polytrauma.

PMID- 19092506
TI  - Performance improvement on the battlefield.
AB  - The Joint Theater Trauma System (JTTS) is a formal system of trauma care designed
      to improve the medical care and outcomes for combat casualties of Operation Iraqi
      Freedom and Operation Enduring Freedom. This article describes the JTTS Trauma
      Performance Improvement Plan and how JTTS personnel use it to facilitate
      performance improvement across the entire continuum of combat casualty care.

PMID- 19092508
TI  - Severe and penetrating traumatic brain injury in the context of war.
AB  - Our data suggests that traumatic brain injury (TBI) may account for up to one
      third of battle-related injuries in today's war. Although the majority of these
      injuries are classified as mild in severity, service members with severe or
      penetrating TBI can be faced with many challenges. Injuries sustained on the
      battlefield require a slightly different approach than the TBI care that is
      traditionally seen in a civilian setting. This article presents the range of care
      that occurs beginning on the battlefield and continuing to state-of-the-art
      rehabilitation within the Department of Defense and Veterans Affairs Polytrauma
      System of Care.

PMID- 19092507
TI  - Implementation of a combat casualty trauma registry.
AB  - The Joint Theater Trauma Registry is a standardized, retrospective data
      collection system for all echelons of combat casualty care. Military-specific
      data elements include expanded demographic data to include military branch,
      service, rank, military occupation, and personal protective equipment. Varying
      data from each echelon are entered into the Joint Theater Trauma Registry,
      version 3. The Joint Theater Trauma Registry, version 3 at the echelon 4 medical
      treatment facility requires routine collection of 367 data elements for each
      casualty, but casualties sustaining burns, deaths, or those with performance
      improvement issues may have more than 450 data elements recorded. Trauma
      registries are powerful tools for process improvement. Collaboration between
      civilian and military trauma programs may foster improvements in registry design
      and data collection for both groups.

PMID- 19092510
TI  - Polytrauma care: a delicate balance for the military nurse case manager.

PMID- 19092511
TI  - Multidisciplinary approach to infection control for combat casualties.
AB  - A multidisciplinary team approach is a necessity when caring for the wounded
      warriors, especially in matters of infection control. Healthcare providers can be
      very resourceful. The healthcare team at an echelon 5 military treatment facility
      made changes in their infection control practices to prevent cross-contamination
      of a multidrug resistant bacterium. Each member was a vital part in the decision
      making process to change behavior and old habits.

PMID- 19092512
TI  - Community hospitals and military sustainment training.
AB  - Military medical personnel are involved in missions at home and abroad that
      require well-sustained skills, particularly relative to trauma response.
      Depending on the Department of Defense base of assignment, exposure to adequate
      volumes of patients with acute injury is diminishing. This article presents
      information on a civilian-military alliance in Maricopa County, Arizona, that is
      forging new territory to assist military medical personnel in getting the hands
      on experiences required to maintain current skills and acquire new ones.

PMID- 19092513
TI  - Interventions for marital discord in military couples: strengthening the home
      front.
AB  - This article discusses the use of role-exit theory within military couples as
      they attend counseling for martial discord. The adjustment of roles by both
      members of the marriage during a military deployment can create tension on the
      soldier's return. The goal of counseling is to assist the couples in regaining a
      balance in their marriage through cohesion and generating comfort in the roles
      assumed during deployment and on the soldier's return.A need for flexibility and
      understanding is important for a successful marriage. This need increases in a
      military couple. Frequent changes due to military service do not always correlate
      with the marital cycle, thus creating problems specific to military couples. With
      the current operational tempo of today's military, couples are feeling the strain
      of deployment and its effects on their roles within the marriage.

PMID- 19092514
TI  - What about the children? Special administration concerns.

PMID- 19092515
TI  - What about the children? Special administration concerns.

PMID- 19092516
TI  - The nursing strategy officer: a new and evolving role.

PMID- 19092517
TI  - Differences between pediatric registered nurses' perception of organizational
      support, intent to stay, workload, and overall satisfaction, and years employed
      as a nurse in magnet and non-magnet pediatric hospitals: implications for
      administrators.
AB  - Much is understood about the issues that nurses believe impact their work
      environment and how Magnet hospitals have better organizational and patient
      outcomes. The majority of these large-scale studies have not included large
      numbers of nurses who care for children. In addition, we know little about how
      nurses perceive their work environment as their years in nursing increase. This
      study used a secondary analysis of survey responses from pediatric staff nurses
      to determine (1) whether there were differences in nurses' perceptions of
      organizational support, workload, intent to stay, and overall satisfaction within
      Magnet and non-Magnet hospitals, and (2) whether there were differences in these
      responses as the years in nursing increased. Findings indicate that Magnet nurses
      perceive a better work environment than do nurses from non-Magnet hospitals, and
      that for nurses in their first year as a nurse and for those nurses who have been
      a nurse for 15 years or longer believe their work environment is more supportive.
      The implications for nurse administrators include finding ways to keep new nurses
      engaged and satisfied after that initial "honeymoon" feeling about their new
      profession as well as providing further evidence of the value Magnet provides an
      institution.

PMID- 19092518
TI  - Pediatric environmental health and nursing leadership.
AB  - Children of poverty and children of industrialization share problems inherent in
      their vulnerability to environmental conditions and their dependence on leaders
      to protect them. Children are often the silent sentinels of changing conditions.
      Unable to articulate their concerns, and possessing immature physiologic systems,
      the very young are vulnerable to disease. Sophisticated and sustainable societies
      can be measured in part by the health of their children; nursing leaders have the
      vision, authenticity, and power to influence a broad constituency. This article
      discusses the impact of the environment on children's health and the important
      role of nurse leaders.

PMID- 19092519
TI  - Linking equitability to quality: the development of a pediatric nursing e-quality
      measure.
AB  - Over the past decade, many initiatives have been directed toward eliminating
      racial and ethnic disparities in healthcare. Despite these efforts, the 2007
      National Healthcare Disparities Report revealed that overall disparities in
      healthcare quality and access have not decreased. Although the disparities
      described vary in magnitude by category and population, they were identified in
      almost every aspect of healthcare. Improving the quality of care may not reduce
      disparities; therefore, ensuring the collection of better patient reported race
      and ethnicity data, whereas linking it to clinical performance may be one of the
      first challenges to overcome. Eliminating disparities in healthcare is
      particularly important in the provision of pediatric care because children of
      immigrant families are the fastest growing sector of the pediatric population in
      the United States. This article describes an approach to the stratification of
      nursing-sensitive measures by race, ethnicity, and insurance group, which
      integrally links cultural competence to quality of care, identifies disparities
      in patient outcomes related to nursing care, and informs the development of
      tailored interventions to meet the needs of diverse patients and their families.

PMID- 19092520
TI  - Children's Perceptions of Healthcare Survey.
AB  - BACKGROUND: Few validated pediatric tools exist to directly gather data about
      children's perceptions of their own healthcare; parent surveys are typically used
      as proxies. A psychometrically sound, child-focused survey captures children's
      unique perceptions for quality improvement. OBJECTIVES: This study developed and
      evaluated reliability of a survey, assessed score differences by children's age,
      and compared the responses of children and parents. METHOD: The Children's
      Perceptions of Healthcare Survey was developed for inpatient and outpatient
      quality improvement. Following expert review, the tool was administered to 237
      parent-child dyads at the time of discharge from an inpatient pediatric unit (n =
      121) and after outpatient clinic visits (n = 116). Responses were analyzed and
      compared. RESULTS: Internal consistency reliability for the tool was high
      (child/adolescents: alpha = .84; parents: alpha = .86), with no significant
      differences by child age or child gender. Parent and child scores were
      significantly correlated (r = 0.29, P < .001). About half of parents' scores were
      higher than their children's scores. DISCUSSION: This tool worked well to collect
      data from a wide age range of children across healthcare settings. Children's
      perceptions were unique; involving children in care assessment is worthwhile and
      captures insights missed when only parents are surveyed. The Children's
      Perceptions of Healthcare Survey is a valid, psychometrically sound tool to
      capture children's unique perspectives regarding their healthcare and may be
      useful for system quality improvement.

PMID- 19092522
TI  - Pediatric medication safety: the power of the team.
AB  - Children are at risk from adverse medication events. National attention has been
      focused on medication errors resulting from medication formulation issues to
      medication administration issues. There is a compelling need to improve
      strategies that will result in reduced risk as well as reduced harm to children
      from medication mishaps. Opportunity exists to enhance the efforts of national
      medication safety groups by identifying teams at every level of care that might
      best apply research findings to pediatric medication safety processes. This
      review describes the evidence basis of pediatric medication safety strategies and
      the national teams that substantially influence the application of these
      strategies at facility, unit, and community levels, and it asserts that
      medication safety strategies matter most at the level of the child.

PMID- 19092521
TI  - Reducing hospital expenditures with the COPE (Creating Opportunities for Parent
      Empowerment) program for parents and premature infants: an analysis of direct
      healthcare neonatal intensive care unit costs and savings.
AB  - More than 500,000 premature infants are born in the United States every year.
      Preterm birth results in a multitude of negative adverse outcomes for children,
      including extended stays in the neonatal intensive care unit (NICU),
      developmental delays, physical and mental health/behavioral problems, increased
      medical utilization, and poor academic performance. In addition, parents of
      preterms experience a higher incidence of depression and anxiety disorders along
      with altered parent-infant interactions and overprotective parenting, which
      negatively impact their children. The costs associated with preterm birth are
      exorbitant. In 2005, it is estimated that preterm birth cost the United States
      $26.2 billion. The purpose of this study was to perform a cost analysis of the
      Creating Opportunities for Parent Empowerment (COPE) program for parents of
      premature infants, a manualized educational-behavioral intervention program
      comprising audiotaped information and an activity workbook that is administered
      to parents in 4 phases, the first phase commencing 2 to 4 days after admission to
      the NICU. Findings indicated that the COPE program resulted in cost savings of at
      least $4864 per infant. In addition to improving parent and child outcomes,
      routine implementation of COPE in NICUs across the United States could save the
      healthcare system more than $2 billion per year.

PMID- 19092523
TI  - Implementation of patient safety rounds in a children's hospital.
AB  - Many healthcare organizations have implemented patient safety initiatives aimed
      at creating a safer healthcare environment. At North Carolina Children's Hospital
      at University of North Carolina Hospitals, patient safety rounds were established
      in the fall of 2005. Rounds are held weekly and involve all members of the
      healthcare team. Senior leadership actively participates and helps staff seek out
      solutions for the identified issues. Within the first year of operation, 191
      issues were identified, of which 58% were resolved. Rounds continue to occur and
      have expanded over to the Women's services. Other initiatives such as Just
      Culture and Six Sigma have been established and help further cultivate a climate
      that strives toward optimizing patient safety.

PMID- 19092524
TI  - On the scene at Children's Hospitals and Clinics of Minnesota.
AB  - Transformational nursing leadership requires innovation and best practice
      synthesis to engage and advance nursing practice and outcomes. Children's
      Hospital and Clinics of Minnesota is creating a sustainable culture of patient
      safety that expects collaborative practice involving families and all clinical
      disciplines. Leadership and practice structures are essential to ensure high
      reliability processes and achieve breakthrough performance. Several
      infrastructural paths are described to illustrate how Children's Hospitals and
      Clinics of Minnesota integrates multiple approaches toward a common purpose of
      clinical excellence.

PMID- 19092525
TI  - Building intervention responses for sexually exploited, runaway youth.
AB  - The health and safety of runaway, sexually exploited youth is a national concern
      and challenge. This article describes how nursing administrators can support
      outreach to vulnerable and difficult to serve populations, develop collaborations
      with community agencies, and promote the delivery of healthcare.

PMID- 19092526
TI  - Children's Cancer Network: providing hope and healing to children and families.
AB  - Children's Cancer Network is an Arizona-based nonprofit organization that
      provides financial and psychosocial assistance to children and families dealing
      with pediatric cancer. Through patient and family services and/or patient and
      family education, this organization strives to address the needs of this special
      population identified by the pediatric oncology healthcare professionals. The
      outcome of these programs has been overwhelmingly positive for the patients and
      families.

PMID- 19092527
TI  - Expediting care for children: advanced practice nurses as short stay
      hospitalists.
AB  - Advanced practice nurses (APNs) diagnose and treat acute conditions in children
      that produce outcomes of efficient, cost effective, timely, and satisfying
      healthcare to children, families and referring providers. Expediting care for
      children with acute illnesses in hospital settings by applying the knowledge and
      skills of nurse practitioners is a smart use of resources.

PMID- 19092528
TI  - Completing the circle: providing comprehensive care to children with special
      healthcare needs.
AB  - Providing a medical home for children with special healthcare needs presents
      challenges such as allowing time during the office visit to address the child's
      and parent's concerns, the provision of comprehensive medical care, and
      identifying resources to support these children in the community. The care
      coordinator serves as a link between the child/family, physician, school, and
      community resource to promote communication and prevent duplication of services
      to ensure optimal outcomes for these children. A plan of care or medical summary
      is developed by the care coordinator with input from the parent/child,
      pediatrician, specialists, and allied healthcare personnel to use as a
      communication tool with staff/physicians in the emergency room, new specialists,
      schools, and community agencies to promote access to services.

PMID- 19092530
TI  - Neither seen nor heard: why we need a child-friendly electronic health record.
AB  - Pediatric practice is like no other. It has its own language, its own data
      requirements, and its own compliance and privacy imperatives. Traditional
      electronic health records (EHRs), which are designed for adult care, are
      insufficient for supporting efficient, effective pediatric care. This article
      examines the unique data needs of pediatric care and suggests ways in which a
      pediatric-enabled EHR could support them.

PMID- 19092529
TI  - Preparing pediatric nurse leaders for practice.
AB  - The growing prevalence of chronic conditions in childhood underscores the urgent
      need to educate pediatric nurse leaders to address the complex issues these
      children and families face. This article describes a model of graduate education
      for preparing pediatric nurse leaders who are equipped to manage and advocate for
      these children and families. Fifty-one master's prepared graduates completed a
      Strategic Plan Needs Assessment Survey in 2007 and were asked to indicate
      specific clinical and leadership competencies that they perceived were essential
      for pediatric nurse leaders in their areas of practice. Results revealed the
      highest priority for continuing education and outreach regarding pediatric health
      to be clinical updates and management of children with special healthcare needs
      (CSHCN), followed by health promotion for CSHCN and care coordination/case
      management. The highest priority for continuing education and outreach regarding
      leadership in pediatrics was evidence-based practice, followed by team
      care/interdisciplinary practice. The challenge for current nurse leaders is to be
      cognizant of the urgent need to prepare and retain future pediatric nurse leaders
      who are experts in the care of CSHCN and their families.

PMID- 19092531
TI  - Helping the chief nursing officer understand nurse practitioners in roles that
      care for pediatric patients.

PMID- 19092532
TI  - Team of three.

PMID- 19092533
TI  - Complex regional pain syndrome: teatment and rehabilitation options.

PMID- 19092534
TI  - Safe strategies for lifting large patients.

PMID- 19092535
TI  - Taking an interdisciplinary team approach to rehabilitation after a TBI.

PMID- 19092536
TI  - Fly high in Air Force nursing.

PMID- 19092537
TI  - Wake up to a career in PACU nursing.

PMID- 19092538
TI  - Be someone's angel: a long-term-care nurse.

PMID- 19092539
TI  - Make the connections: become an online educator.

PMID- 19092540
TI  - Diabetes education nurses handle complexity with care.

PMID- 19092542
TI  - The nurse liaison: quietly working behind the scenes.

PMID- 19092543
TI  - Resume do's and don'ts.

PMID- 19092545
TI  - What's the attraction of Magnet hospitals?

PMID- 19092546
TI  - All the comforts of home--away from home.

PMID- 19092548
TI  - What's the state of interstate licensure?

PMID- 19092549
TI  - What do studies of the nursing literature tell us?

PMID- 19092550
TI  - Translating the diabetes prevention program to primary care: a pilot study.
AB  - BACKGROUND: Research on the translation of efficacious lifestyle change programs
      to prevent type 2 diabetes into community or clinical settings is needed.
      OBJECTIVE: The objective of this study was to examine the reach, implementation,
      and efficacy of a 6-month lifestyle program implemented in primary care by nurse
      practitioners (NPs) for adults at risk of type 2 diabetes. METHODS: The NP sites
      (n = 4) were randomized to an enhanced standard care program (one NP and one
      nutrition session) or a lifestyle program (enhanced standard care and six NP
      sessions). These NPs recruited adults at risk of diabetes from their practice (n
      = 58), with an acceptance rate of 70%. RESULTS: The program reached a diverse,
      obese, and moderately low income sample. The NPs were able to successfully
      implement the protocols. The average length of the program was 9.3 months.
      Attendance was high (98%), and attrition was low (12%). The NPs were able to
      adopt the educational, behavioral, and psychosocial strategies of the
      intervention easily. Motivational interviewing was more difficult for NPs. Mixed
      model repeated-measures analysis indicated significant trends or improvement in
      both groups for nutrition and exercise behavior. Participants of the lifestyle
      program demonstrated trends for better high-density lipoprotein (HDL) and
      exercise behavior compared with the enhanced standard care participants. Twenty
      five percent of lifestyle participants met treatment goals of 5% weight loss
      compared with 11% of standard care participants. DISCUSSION: A lifestyle program
      can be implemented in primary care by NPs, reach the targeted population, and be
      modestly successful. Further research is indicated.

PMID- 19092552
TI  - The Kilauea Volcano adult health study.
AB  - BACKGROUND: Millions of people reside near active volcanoes, yet data are limited
      on effects to human health. The Kilauea Volcano is the largest point source for
      sulfur dioxide in the United States, releasing air pollution on nearby
      communities since 1983. OBJECTIVE: : The objectives of this study were to provide
      the first population-based epidemiological estimates and qualitative descriptions
      of cardiorespiratory health effects associated with volcanic air pollution.
      METHODS: An environmental-epidemiological design was used. Exposure levels of
      Kilauea's air pollutants were determined by environmental sampling. Prevalence
      estimates of cardiorespiratory health effects in adults were measured (N = 335)
      and compared between an exposed and nonexposed reference community. Descriptions
      of the human-environment interaction with the long-standing eruption were
      recorded from informants in the natural setting. RESULTS: Ambient and indoor
      concentrations of volcanic air pollution were above the World Health
      Organization's recommended exposure levels. There were statistically significant
      increased odds associated with exposure for self-reported cough, phlegm,
      rhinorrhea, sore and dry throat, sinus congestion, wheezing, eye irritation, and
      diagnosed bronchitis. Thirty-five percent of the informants perceived that their
      health was affected by the eruption, mainly current and former smokers and those
      with chronic respiratory disease. DISCUSSION: Hypotheses were supported regarding
      particulate air pollution and the association with adverse cardiovascular
      functioning. This emerging environmental health issue is under continuing
      investigation.

PMID- 19092551
TI  - Effects of a nurse-managed program on hepatitis A and B vaccine completion among
      homeless adults.
AB  - BACKGROUND: Hepatitis B virus (HBV) infection constitutes a major health problem
      for homeless persons. Ability to complete an HBV vaccination series is
      complicated by the need to prioritize competing needs, such as addiction issues,
      safe places to sleep, and food, over health concerns. OBJECTIVES: The objectives
      of this study were to evaluate the effectiveness of a nurse-case-managed
      intervention compared with that of two standard programs on completion of the
      combined hepatitis A virus (HAV) and HBV vaccine series among homeless adults and
      to assess sociodemographic factors and risk behaviors related to the vaccine
      completion. METHODS: A randomized, three-group, prospective, quasi-experimental
      design was conducted with 865 homeless adults residing in homeless shelters, drug
      rehabilitation sites, and outdoor areas in the Skid Row area of Los Angeles. The
      programs included (a) nurse-case-managed sessions plus targeted hepatitis
      education, incentives, and tracking (NCMIT); (b) standard targeted hepatitis
      education plus incentives and tracking (SIT); and (c) standard targeted hepatitis
      education and incentives only (SI). RESULTS: Sixty-eight percent of the NCMIT
      participants completed the three-series vaccine at 6 months, compared with 61% of
      SIT participants and 54% of SI participants. NCMIT participants had almost 2
      times greater odds of completing vaccination than those of participants in the SI
      program. Completers were more likely to be older, to be female, to report fair or
      poor health, and not to have participated in a self-help drug treatment program.
      Newly homeless White adults were significantly less likely than were African
      Americans to complete the vaccine series. DISCUSSION: The use of vaccination
      programs incorporating nurse case management and tracking is critical in
      supporting adherence to completion of a 6-month HAV/HBV vaccine. The finding that
      White homeless persons were the least likely to complete the vaccine series
      suggests that programs tailored to address their unique cultural issues are
      needed.

PMID- 19092553
TI  - Testing a theoretical model of perceived self-efficacy for cancer-related fatigue
      self-management and optimal physical functional status.
AB  - BACKGROUND: Critical gaps exist in the understanding of cancer symptoms,
      particularly for cancer-related fatigue (CRF). Existing theories and models do
      not examine the key role perceived self-efficacy (PSE) plays in a person's
      ability to manage symptoms. OBJECTIVES: The objective of this study was to test
      the hypothesis that physical functional status (PFS) is predicted through patient
      characteristics, CRF, other symptoms, and PSE for fatigue self-management in
      persons with cancer. METHODS: This study is a secondary data analysis from the
      baseline observation of two randomized control trials. The combined data set
      includes 298 participants who were undergoing a course of chemotherapy. Key
      variables included physiological and contextual patient characteristics, the
      severity from CRF and other symptoms, PSE, and PFS. Path analysis examined the
      relationships among the variables in the proposed theoretical model. RESULTS:
      Persons with cancer reported CRF as the most prevalent symptom among a mean of
      7.4 other concurrent symptoms. The severity from CRF had a direct and indirect
      effect on PFS, with CRF having a direct adverse impact on PFS (t = -7.02) and an
      indirect adverse effect as part of the severity from the other symptoms (t =
      9.69), which also adversely impacted PFS (t = -2.71). Consistent with the
      proposed theoretical model, PSE had a positive effect on the PFS (t = 2.87) of
      persons with cancer while serving as a mediator between CRF severity and PFS.
      DISCUSSION: Cancer-related fatigue is prevalent and related to the presence of
      other symptoms, and PSE for fatigue self-management is an important factor
      influencing CRF and PFS. A foundation is provided for future intervention studies
      to increase PSE to achieve optimal PFS in persons with cancer.

PMID- 19092554
TI  - The Control Attitudes Scale-Revised: psychometric evaluation in three groups of
      patients with cardiac illness.
AB  - BACKGROUND: Perceived control is a construct with important theoretical and
      clinical implications for healthcare providers, yet practical application of the
      construct in research and clinical practice awaits development of an easily
      administered instrument to measure perceived control with evidence of reliability
      and validity. OBJECTIVE: To test the psychometric properties of the Control
      Attitudes Scale-Revised (CAS-R) using a sample of 3,396 individuals with coronary
      heart disease, 513 patients with acute myocardial infarction, and 146 patients
      with heart failure. METHODS: Analyses were done separately in each patient group.
      Reliability was assessed using Cronbach's alpha to determine internal
      consistency, and item homogeneity was assessed using item-total and interitem
      correlations. Validity was examined using principal component analysis and
      testing hypotheses about known associations. RESULTS: Cronbach's alpha values for
      the CAS-R in patients with coronary heart disease, acute myocardial infarction,
      and heart failure were all greater than .70. Item-total and interitem correlation
      coefficients for all items were acceptable in the groups. In factor analyses, the
      same single factor was extracted in all groups, and all items were loaded
      moderately or strongly to the factor in each group. As hypothesized in the final
      construct validity test, in all groups, patients with higher levels of perceived
      control had less depression and less anxiety compared with those of patients who
      had lower levels of perceived control. CONCLUSION: This study provides evidence
      of the reliability and validity of the 8-item CAS-R as a measure of perceived
      control in patients with cardiac illness and provides important insight into a
      key patient construct.

PMID- 19092555
TI  - A dimensional analysis of patient-centered care.
AB  - BACKGROUND: Patient-centered care (PCC) is a poorly conceptualized phenomenon and
      can indicate anything from soothing room design, emotional support of patients,
      customization of meals, to support of patient decision making. This inconsistency
      across the clinical and research literature makes the application of PCC
      difficult. OBJECTIVES: The objective of this study was to identify dimensions of
      PCC as found in the literature. METHODS: A dimensional analysis of PCC was
      conducted from 69 clinical and research articles published from 2000 to 2006.
      Coding of the literature for the perspective, context, conditions, process, and
      consequences of PCC was completed. These codes were used to determine literature
      selected for inclusion, organize article content, and frame the delineation of
      PCC. RESULTS: Alleviating vulnerabilities, consisting of both compromised
      physiological states and threats to individual identity, was constant throughout
      the literature. Therapeutic engagement was the process sustaining the patient
      during an illness episode that necessitated service use and involved allocating
      time, carrying out information practices, knowing the patient, and developing a
      relationship. This process occurs during nurse-patient interaction, sustained
      during successive interactions, and reinforced by the information practices of a
      particular setting. DISCUSSION: The interaction between nurse and patient is
      central to the effective study and application of PCC. Appropriate use of PCC can
      improve study outcomes and measurements by clarifying the variables involved, and
      PCC holds great promise to frame patient outcome and satisfaction research by
      analyzing how and with what effect nurses alleviate patient vulnerability.
      Moreover, consideration of information practices as a critical supporting
      structure of nurse-patient interaction can be explored.

PMID- 19092556
TI  - Self-reported sleep disturbance of patients with heart failure in Taiwan.
AB  - BACKGROUND: Western research studies have found that sleep disturbances reduced
      quality of life and daily functioning of patients with heart failure; however,
      information about sleep disturbance is lacking in Taiwanese people with heart
      failure. OBJECTIVES: The objective of this study was to investigate predictors of
      self-reported sleep disturbances in Taiwanese people with heart failure. The
      hypothesis was that health-related quality of life (HRQOL) could have significant
      effect on sleep disturbances, after controlling for demographics, heart failure
      characteristics, and health-related characteristics. METHODS: A cross-sectional,
      descriptive, correlational design was used. A purposive sample of 125
      participants was recruited from the outpatient departments of two hospitals
      located in southern Taiwan. Participants were interviewed individually to
      complete the Pittsburgh Sleep Quality Index, Kansas City Cardiomyopathy
      Questionnaire, Charlson Comorbidity Index, and Perceived Health Scale
      instruments. RESULTS: Self-reported sleep disturbances were prevalent (74%) among
      people with heart failure in Taiwan. Five predictors were identified using
      hierarchical multiple regression analyses with forward methods, accounting for
      26.9% of variance in sleep disturbances. They were education, New York Heart
      Association functional classification, perceived health, HRQOL social
      functioning, and physical symptoms. After controlling for demographics, heart
      failure characteristics, and health-related characteristics, the analysis showed
      that two variables of HRQOL accounted for 9.8% of the variance in sleep
      disturbances. DISCUSSION: The importance of ongoing screening for sleep
      disturbances in people with heart failure is highlighted based on the study
      findings about the prevalence of sleep disturbances among the participants in
      this study. Healthcare providers must understand the often multifactorial nature
      of sleep disturbances to achieve a better and more effective management.

PMID- 19092557
TI  - Real-time intraoperative computed tomography to assist cochlear implant placement
      in the malformed inner ear.
AB  - OBJECTIVE: Cochlear implantation is increasingly being performed in children with
      inner ear malformations. In severe cochleovestibular anomalies, such as severe
      partitioning defects and common cavity dysplasia, positioning of the electrode
      array can be hazardous, with inadvertent placement into the internal auditory
      canal (IAC) or carotid canal being well known. We describe a case in which real
      time intraoperative computed tomographic scanning was used to help achieve proper
      electrode positioning in a child with a severe malformation. PATIENT: Child with
      common cavity malformations undergoing cochlear implantation. INTERVENTION:
      Intraoperative computed tomography used during implantation procedure. MAIN
      OUTCOME MEASURE: Use of technique in determining electrode position. RESULTS: A
      10-year-old patient with bilateral common cavity malformations presented with
      declining performance in a functioning implant placed 7 years earlier. The family
      elected implantation of the contralateral ear. Via a posterior labyrinthotomy
      approach, a straight array was placed into the common cavity. Intraoperative
      computed tomographic scanning was immediately performed on the operating room
      table, showing that the array was in the IAC. A second attempt with a different
      insertion angle also resulted in IAC placement. In a third attempt, the electrode
      was advanced as a loop, grasping the tip through an adjacent second
      labyrinthotomy. Computed tomography confirmed good position against the outer
      wall of the cavity. CONCLUSION: Real-time intraoperative computed tomography is a
      new technology with many potential applications in surgery. In our patient, it
      allowed rapid and accurate determination of electrode position and helped achieve
      ideal placement in a severely malformed inner ear.

PMID- 19092558
TI  - Postoperative non-echo-planar diffusion-weighted magnetic resonance imaging
      changes after cholesteatoma surgery: implications for cholesteatoma screening.
AB  - OBJECTIVES: Diffusion-weighted (DW) magnetic resonance imaging (MRI) is emerging
      as an alternative to second-look surgery in ruling out residual or recurrent
      disease after cholesteatoma eradication. However, the DW MRI appearances of
      postoperative or inflammatory mucosal changes have not been well investigated,
      thus rendering the interpretation of postoperative DW MRI difficult in the
      presence of mucosal reactions. We investigated the turbo-spin echo (TSE) DW MRI
      changes of the middle ear and mastoid mucosa after cholesteatoma surgery and
      compared these with the TSE DW MRI features of cholesteatoma with an aim to
      identify a rapid and cost-effective purely DW MRI sequence that can be used to
      screen for cholesteatoma. STUDY DESIGN: A prospective comparative study. SETTING:
      A tertiary referral center in Western Australia. PATIENTS: Patients undergoing
      revision or second-look cholesteatoma surgery. INTERVENTION: Patients underwent 3
      to 6 monthly half-Fourier-acquisition single-shot turbo-spin-echo TSE DW MRI
      before their second surgery. The MRI findings were then correlated with the
      intraoperative findings at second-look surgery 6 to 17 months after primary
      surgery or of revision surgery in the cases that were referred from other
      centers. MAIN OUTCOME MEASURE: Detection of cholesteatoma and noncholesteatoma
      mucosal changes on TSE DW MRI, compared with the gold standard of findings at
      second surgery. RESULTS: Twenty-two patients underwent 23 second-look or revision
      procedures. All patients had DW MRI before their "second-look" or revision
      surgery. TSE DW MRI detected cholesteatomas in 7 patients whom all had disease
      confirmed at second-look or revision surgery. In 16 cases shown to be negative on
      DW MRI for cholesteatoma, all were confirmed to be disease-free on second-look
      surgery. Cholesteatomas were shown to produce a TSE DW MRI signal clearly
      distinct from the spectrum of imaging findings encountered in postoperative
      mucosal changes. CONCLUSION: TSE DW MRI holds great promise in screening for
      cholesteatoma as an alternative to exploratory second-look surgery.

PMID- 19092559
TI  - Reversible electrocochleographic abnormalities in superior canal dehiscence.
AB  - OBJECTIVE: Electrocochleography (ECoG) is often used in the evaluation of
      episodic vertigo, and abnormal findings are commonly thought to be due to
      endolymphatic hydrops. We have observed that a number of patients with abnormal
      ECoG were ultimately found to have superior semicircular canal dehiscence (SSCD).
      Therefore, we examined the electrocochleographic findings in a series of patients
      with documented SSCD. STUDY DESIGN: Retrospective case series. SETTING: Academic
      medical center. PATIENTS: Seven adult patients with unilateral SSCD and 4
      patients with bilateral SSCD who underwent tympanic ECoG as part of a diagnostic
      or preoperative evaluation that also included vestibular-evoked myogenic
      potentials (VEMPs). INTERVENTIONS: Patients underwent audiometric testing, ECoG,
      VEMP, and high-resolution temporal bone computed tomography reformatted to
      optimally view the superior semicircular canal. Five patients underwent superior
      canal obliteration. Postoperative VEMP and ECoG were performed in 4 of these
      patients. Intraoperative continuous ECoG was performed in 1 patient. MAIN OUTCOME
      MEASURES: Summating potential to action potential (SP/AP) ratio on ECoG. RESULTS:
      Fourteen of 15 ears confirmed to have SSCD on computed tomographic imaging were
      found to have an elevated SP/AP ratio (defined as >0.40). In one patient with
      bilateral SSCD, the ear with the radiographically less severe dehiscence had an
      SP/AP ratio of 0.40, at the upper limit of normal, and a normal VEMP threshold.
      In all 4 patients who underwent obliteration of the dehiscent canal, and for whom
      postoperative test results were available, the SP/AP ratio normalized in the
      operated ear. In the 1 patient who underwent intraoperative ECoG, the SP/AP ratio
      normalized immediately after canal occlusion. CONCLUSION: An elevated SP/AP ratio
      seems to be a consistent finding in SSCD syndrome and, like the other abnormal
      audiometric and electrophysiologic findings associated with the syndrome,
      normalizes after surgical correction. Elevation of the SP/AP ratio has
      historically been associated with endolymphatic hydrops. The present findings
      expand the differential diagnosis of an abnormal ECoG and may shed light on the
      origin of an elevated summating potential.

PMID- 19092560
TI  - The Portuguese version of Mini-Tinnitus Questionnaire: brief screening test for
      assessment of tinnitus-induced stress.
AB  - HYPOTHESIS: The Portuguese version of Mini-Tinnitus Questionnaire (Mini-TQ) is as
      valid as the English version to assess tinnitus-associated distress in the
      Portuguese-speaking population. BACKGROUND: Tinnitus is a major symptom in ENT
      practice affecting subjects in all demographic groups. Our objective is to
      validate a Portuguese version of Mini-TQ (Mini-TQ-pv) to be used in clinical
      practice and research. METHODS: Mini-TQ-pv was administered to 51 patients with
      chronic tinnitus. Statistical analysis was done to determine the psychometric
      properties of the instrument. RESULTS: After double translation, face and content
      validity were confirmed by high internal consistency (Cronbach alpha = 0.861) and
      significant correlation between individual items and total score. The
      questionnaire was easy and quick to administer (2.57 min). CONCLUSION: We provide
      a suitable Mini-TQ-pv to be used in the assessment of Portuguese-speaking
      patients with tinnitus.

PMID- 19092561
TI  - Tophaceous gout of the middle ear.

PMID- 19092562
TI  - Group A streptococcal infection of an intramuscular venous malformation: a case
      report and review of the literature.
AB  - Intramuscular venous malformations are uncommon benign masses of vascular origin
      that can occur anywhere in the body. They can be small and clinically
      insignificant or can be large and violate tissue planes and viscera. Presentation
      is as variable as the extent of the lesions. They can be diagnosed as a result of
      local pain and swelling or as incidental findings. Rarely, venous malformations
      can get infected and present with fever or other more severe systemic symptoms.
      The literature is sparse regarding infection of intramuscular venous
      malformations. This case describes the presentation, diagnosis, and management of
      a patient with group A streptococcal infection of a previously undiagnosed
      intramuscularvenous malformation in a patient who presented to our pediatric
      emergency department.

PMID- 19092563
TI  - Thoracic spine compression fracture during isoniazid-induced seizures: case
      report.
AB  - We report here an 11-year-old previously healthy girl with isoniazid intoxication
      who sustained a seizure-induced thoracic compression fracture. The following
      might be the first such case reported in the medical literature. Isoniazid
      toxicity should be suspected in any patient who comes to the emergency department
      with refractory seizures and metabolic acidosis. Forceful muscle contractions
      during a convulsive seizure can result in vertebral compression fracture,
      especially in the midthoracic region. A complaint of back pain after isoniazid
      induced seizures in patients raises a strong suspicion of vertebral fracture and
      should be evaluated radiologically.

PMID- 19092564
TI  - Ethmoid mucocele presenting as an orbital mass.
AB  - This is a case of an 11-year-old male with an ethmoid sinus mucocele who
      presented to our emergency department with an orbital mass. This mucocele was
      most likely related to an ipsilateral orbital subperiosteal abscess that required
      endoscopic drainage 9 years ago. Mucoceles are mucus-filled, epithelial-lined
      sacs that slowly develop in the paranasal sinuses when sinus drainage is
      obstructed by inflammatory processes, trauma, or prior surgery. They are rare in
      children and should be suspected in patients with progressive headache or orbital
      complaints.

PMID- 19092565
TI  - Report of 4 cases of testicular rupture in adolescent boys secondary to sports
      related trauma.
AB  - Testicular rupture is a rare entity in children and adolescents. This is due to
      the smaller size of the testicles in these patients, the well-protected location
      of the testicles, and the high degree of mobility of these organs. We present 4
      cases of testicular rupture occurring in preadolescent and adolescent boys over
      an 11-month period in a tertiary care pediatric emergency department.

PMID- 19092566
TI  - Esophageal foreign body: a case of a neonate with stridor.
AB  - We present a case of a 7-week-old female with a 3-week history of progressively
      worsening stridor who was admitted to rule out a congenital anomaly in the airway
      or vasculature. After 3 different imaging modalities, we discovered an esophageal
      foreign body causing esophagitis and proximal airway compression.Young infants
      with symptoms of stridor, wheezing, or retractions will often have a common
      diagnosis such as a viral infectious etiology, or in rarer cases an anatomic
      anomaly. This case illustrates that the presence of a foreign body must still
      remain on the differential, even in this age group.

PMID- 19092567
TI  - Atlantoaxial rotary subluxation after minor trauma.
AB  - We present a case of atlantoaxial rotary subluxation after a minor injury managed
      by manual reduction under sedation. Atlantoaxial rotary subluxation should be
      considered in a child with inability or unwillingness to turn their head when
      history and physical examination do not suggest torticollis of benign etiology.
      In our discussion, we review etiology, diagnosis, as well as pre- and in-hospital
      management.

PMID- 19092568
TI  - Pediatric emergency medicine: legal briefs.

PMID- 19092569
TI  - Management of anaphylaxis in children.
AB  - Anaphylaxis is a severe, life-threatening immunoglobulin E (IgE)-mediated
      hypersensitivity reaction. The key to successful management of anaphylaxis
      involves rapid diagnosis, assessment, and early initiation of therapy.
      Epinephrine is the undisputed initial therapy for anaphylaxis, and its
      administration should never be delayed. In most cases, additional interventions
      such as oxygen therapy, fluid resuscitation, beta-agonists, antihistamines, and
      corticosteroids should be strongly considered. Although hospital course must be
      individualized to meet each patient's needs, a minimum of 4 to 6 hours of
      observation period after complete symptom resolution may be reasonable to monitor
      for recurrence of symptoms and biphasic reaction. Before discharge, every patient
      should receive patient education about anaphylaxis, a prescription for self
      injectable epinephrine, and instructions for follow-up care.

PMID- 19092571
TI  - Urgency classification methods for emergency department visits: do they measure
      up?
AB  - Across the United States, emergency departments (EDs) are plagued by overcrowding
      and its deleterious effects. Consequently, investigators have attempted to
      identify a subset of nonurgent patients who could potentially be managed in
      alternative settings to help alleviate the burden of overcrowding. Previous
      authors have used several methods to define ED visit urgency; however, the lack
      of a single valid method has resulted in widely variable estimates of nonurgent
      ED use. Accurate identification of nonurgent ED visits is necessary to compare
      nonurgent populations across health care settings and design safe, effective
      interventions aimed at reducing ED overcrowding. In this paper, we review the
      currently used methods for the classification of ED visit urgency, discuss the
      implications of measurement of ED urgency for health care stakeholders, and
      suggest future directions for the feasible, practical measurement of ED urgency.

PMID- 19092573
TI  - ECGs in the ED.

PMID- 19092572
TI  - A teenager with focal weakness.

PMID- 19092575
TI  - Searching for the Holy Grail: a review of markers of tissue perfusion in
      pediatric critical care.
AB  - Goal-directed therapy has become the key to resuscitating critically ill patients
      since 2001. However, the ideal marker to guide pediatric resuscitation has
      remained elusive.The ideal marker is specific, sensitive, easy to use, safe,
      validated, and cost-effective. Lactate and base deficit are validated
      prognosticators, but both are affected by confounding conditions and
      resuscitative efforts. Mixed venous oximetry has been successfully used for
      guiding therapy but requires a pulmonary artery catheter for measurement. Central
      venous oximetry, on the other hand, can be more easily measured and is now the
      standard of care in goal-directed therapy for adult septic shock. Pediatric
      literature related to central venous oximetry is still in relative infancy, but
      seems promising. Sublingual capnometry may also prove to be useful, but no
      pediatric research has been published related to this device. Finally, near
      infrared spectroscopy monitoring may be useful in highlighting changes in patient
      conditions, but its use in goal-directed therapy is limited by the wide
      interpatient variability. In summary, the search for the ideal marker of tissue
      perfusion continues, but there is promise on the horizon.

PMID- 19092577
TI  - Resolutions you can keep.

PMID- 19092579
TI  - Methicillin-resistant Staphylococcus aureus: a new pandemic?
AB  - The death rate in the United States is higher for methicillin-resistant
      Staphylococcus aureus (MRSA) than the death rate for AIDS. It has also been
      present for much longer than people realize. It is affecting all groups of
      individuals, children, and adults alike. Moreover, like AIDS, education is the
      key in preventing the spread of this disease. Because skin-to-skin contact is the
      main cause of MRSA transmission, simple good hand washing techniques remain
      crucial. New classes of antibiotics have been approved by the Food and Drug
      Administration for MRSA, as the challenge becomes continued antibiotic
      resistance.

PMID- 19092580
TI  - Breast augmentation motivations and satisfaction: a prospective study of more
      than 3,000 silicone implantations.
AB  - More than 3,000 participants from three large, multi-center, US clinical studies
      of silicone implants (Allergan, Santa Barbara, CA) were asked to rate their
      motivations for breast augmentation surgery prior to implantation. A 5-point
      scale was used to rate the level of importance, ranging from "not at all
      important" to "extremely important." Prior to implantation and 1 year after
      implant surgery, women also rated their level of satisfaction with various
      aspects of their breasts. This article reviews the data collection methods and
      current results of these studies, identifying the patient's motivation for breast
      augmentation surgery and reported post-operative satisfaction.

PMID- 19092582
TI  - Motivating factors for seeking cosmetic surgery: a synthesis of the literature.
AB  - The fascination in physical beauty is becoming more and more prevalent in today's
      society. Beauty in American culture is defined by the media through magazines,
      television, and music. The perfect career, the perfect family, social status, and
      high self-esteem all revolve around having an impeccable figure. Research shows
      that 94% of the covers of women's magazines showcase a woman with a thin physique
      (A. R., Malkin, K., Wornian, & J. C. Chrisler, 1999). Therefore, it is not
      surprising that year after year, millions of people elect for cosmetic surgery.
      According to the , approximately 11.7 million cosmetic surgical and nonsurgical
      procedures were performed and Americans spent $13.2 billion on these procedures.
      This is a 457% increase since 1997. As the demand for elective cosmetic surgery
      continues to rise, it is important for healthcare employees to recognize the
      motive behind the decision to seek cosmetic surgery. The purpose of this
      literature review project was to ascertain those factors that influence or
      motivate patients to seek cosmetic surgery. This project investigated physical,
      psychiatric, and psychosocial factors associated with individuals who undergo
      elective cosmetic surgery. It has been shown that the motivation for cosmetic
      surgery is based on a combination of psychological and emotional factors.
      Researchers surmise that body image, teasing history, and self-esteem were
      associated with motivational factors for those patients who elected to seek
      cosmetic surgery (T. Soest, I. L. Kvalem, K. C. Skolleborg, & H. E. Roald, 2006).
      In addition, the researchers concluded that body dysmorphic disorder, education,
      and culture are also predicting factors in the decision to have cosmetic surgery.

PMID- 19092583
TI  - Postoperative nursing care of the endoscopic nonsyndromic craniosynostosis
      surgery patient.
AB  - Craniosynostosis affects 1 in 2,100 children. The current methods for the
      treatment of craniosynostosis at Rady Children's Hospital, San Diego, are open
      cranial vault remodeling and the minimally invasive endoscopic technique. The
      primary advantages of the minimally invasive endoscopic technique are decreased
      operative time, blood loss, swelling, incision size, and inpatient hospital stay.
      Postoperative helmet therapy is a necessary part of the treatment for the
      refinement of the surgical result. The purpose of this article is to present
      current inpatient and outpatient nursing management considerations in the care of
      infants undergoing the minimally invasive endoscopic technique for the treatment
      of craniosynostosis.

PMID- 19092585
TI  - Clinical photography for the plastic surgery practice--the basics.
AB  - Accurate clinical photography is essential in today's plastic and reconstructive
      surgery practice. Quality photographs are a reflection of the care and attention
      to detail exhibited in the plastic surgery practice, and there should be no
      excuse for poor quality clinical photographs. This article presents basic
      photographic principles. The next article will discuss the office environment and
      steps to set up a photographic studio.

PMID- 19092587
TI  - Is it a cosmetic, a drug, or both? (Or is it soap?).

PMID- 19092588
TI  - Proposed plastic surgical nursing guidelines for the care of the rhinoplasty
      patient.

PMID- 19092589
TI  - Risk factors for surgical site infections.

PMID- 19092590
TI  - The Joint Commission update for peri-operative services-2009.
AB  - As part of its continuous quality improvement efforts, The Joint Commission began
      a standards improvement initiative (SII) in October 2006, the result of which
      will be "felt" by most accredited organizations (ambulatory care organizations,
      critical access hospitals, home care, hospitals, and office-based surgery) on
      January 1, 2009. The remaining organizations (behavioral health, laboratory, and
      long-term care) will go through a similar experience on January 1, 2010. The
      essence of SII was the changes made by The Joint Commission through
      consolidating, rewording, revising, and restructuring of chapters, standards, and
      elements of performance (EPs). Although few new standards have actually been
      added, there are nuances that, if not noted, may cause considerable difficulty to
      organizations during upcoming accreditation surveys. This article discusses SII
      and the standards and EPs that impact and pose "opportunities for improvement"
      for peri-operative services.

PMID- 19092591
TI  - Disruptive behavior-patient safety at risk.

PMID- 19092592
TI  - Five steps to safer healthcare-patient fact sheet.

PMID- 19092593
TI  - Something funny about humor.

PMID- 19092594
TI  - Understanding medical home: a new opportunity for case managers.

PMID- 19092595
TI  - The "medication interest model": an integrative clinical interviewing approach
      for improving medication adherence-part 2: implications for teaching and
      research.
AB  - PURPOSE/OBJECTIVES: Over the past several decades, exciting advances have been
      made in the art and science of teaching clinical interviewing, which are
      supported by an ever-growing evidence base documenting their effectiveness. In
      this second article in a 2-part series, the training and research implications of
      an innovative approach to improving medication adherence based on these
      educational advances--the medication interest model (MIM)--are described. The
      objective is to provide an "insider's view" of how to creatively teach the MIM to
      case managers, as well as design state-of-the-art courses and research platforms
      dedicated to improving medication adherence through improved clinical
      interviewing skills in both nursing and medical student education. PRIMARY
      PRACTICE SETTINGS: The teaching and research design concepts are applicable to
      all primary care settings as well as specialty areas from endocrinology and
      cardiology to psychiatry. FINDINGS/CONCLUSIONS: Evidence-based advances in the
      teaching of clinical interviewing skills such as response-mode research, facilic
      supervision, microtraining, and macrotraining lend a distinctive quality and
      integrative power to the MIM. IMPLICATIONS FOR CASE MANAGEMENT: The model
      delineates several new platforms for training and research regarding the
      enhancement of medication adherence including an approach for collecting
      individual interviewing techniques into manageable "learning modules" amenable to
      competency evaluation and potential certification.

PMID- 19092597
TI  - Hitch up your humor suspenders, case managers.
AB  - PURPOSE/OBJECTIVES: Although case managers must project professionalism, a dash
      of healing humor can accomplish a lot of trust in a little space of time. To show
      how case managers can incorporate humor into case management (CM), the article
      explores beneficial humor-based interventions and sources of unhealthy humor.
      Suspending the garment of good humor are 2 main straps: (1) increasing the
      theoretical knowledge base about healthcare humor for case managers and (2)
      encouraging knowledge transfer through appropriate humorous exchanges up and down
      the care continuum bucket brigade. IMPLICATIONS FOR CASE MANAGEMENT PRACTICE:
      With backgrounds in social work, nursing, therapy, and even doctoring, CM
      practitioners see the soft underbellies of people's lives. From evidence-based
      research, case managers can garner tips for humor tact and identify ways to
      incorporate them into CM practice. Recommendations are elaborated to achieve
      positive outcomes of authentic communication and improving the quality of
      healthcare experiences. Examples include recognizing boundaries of unfunny and
      funny, dignifying and humanizing interactions through levity, responding to age
      groups appropriately, and drawing from client-preference tidbits like
      inspirational songs and humorous stories. Avoiding negative outcomes is
      discussed, especially harming with humor. Five common displays of the humor
      coin's flip side and ethical erosion are presented. FINDINGS/CONCLUSIONS: To aid
      case managers, caregivers, and clients in fortifying their coping mechanisms,
      research findings showcase not only the good but also the bad and the ugly such
      as interventions to avoid. Findings spotlight appropriate uses of humorous
      antics, bells and whistles signaling low humor and high risk, and simple
      takeaways case managers can tuck in their satchels. The article's multipronged
      conclusion is that respectful humor used judiciously can buoy clients' spirits,
      bring spoonfuls of levity to a sea of seriousness, show humility that softens the
      stiff authoritarian semblance of control, and increase clients' confidence that
      their proverbial exposed underbellies are in safe hands. Pile in the little red
      research vehicle with the author on this purposeful journey of jocularity. As the
      slogan goes, many true things are said in jest. Hitch up Your Humor Suspenders is
      one of them.

PMID- 19092599
TI  - Preventing Rehospitalization through effective home health nursing care.
AB  - PURPOSE/OBJECTIVES: To identify strategies to improve patient outcomes and
      prevent rehospitalizations in home healthcare. PRIMARY PRACTICE SETTINGS(S):
      Primarily for home healthcare but can also be a tool for all other fields in
      nursing. FINDINGS/CONCLUSIONS: Through team collaboration and the proper
      resources, patient outcomes can improve and be cost-effective for home healthcare
      agencies despite the changes implemented after the Medicare change in payment for
      services, the prospective payment system. IMPLICATIONS FOR CASE MANAGEMENT
      PRACTICE: The main goal for home healthcare is to improve patient outcomes.
      Nurses experienced in case management can devise creative strategies to ensure
      patient outcomes are met in a cost-effective manner. With continuous changes in
      reimbursement and payment incentives, case managers in every level of care must
      know about, and be responsible for, fiscal initiatives.

PMID- 19092600
TI  - Mark's journey: a study in medicaid palliative care case management.
AB  - PURPOSE/OBJECTIVES: Palliative care and managed care share the goals of providing
      comprehensive patient care in a manner that reflects the goals of the patient
      while controlling the use of ineffective, costly treatments and arranging for
      care in the most appropriate treatment setting. The purpose of this case study is
      to illustrate the integrations of palliative care principles and practices within
      a managed care organization serving Medicaid patients. The Five Principles of
      Palliative Care developed by the Last Acts Task Force are used to structure the
      description of the interventions of the palliative care case management team.
      PRIMARY PRACTICE SETTING: The practice setting is Passport Health Plan, the
      managed care provider for the state Medicaid program in Louisville, Kentucky,
      which serves Jefferson and 15 surrounding Kentucky counties. Care for the patient
      was provided by a nurse and social worker team specializing in palliative care
      case management. FINDINGS/CONCLUSIONS: Palliative care principles and practices
      can be successfully integrated into managed care as a means for providing quality
      end-of-life care, a cost-effective, yet patient-centered, approach to care, and
      an alternative when hospice care is not indicated or available. IMPLICATIONS FOR
      CASE MANAGEMENT PRACTICE: Case management practitioners and organizations and the
      persons they serve can benefit from incorporating palliative care principles and
      practices into mainstream case management practice.

PMID- 19092601
TI  - Do you ever wonder?

PMID- 19092602
TI  - Advocacy and the hospital case manager.

PMID- 19092603
TI  - On preparing for a deposition.

PMID- 19092604
TI  - Gifts and gratuities for the case manager.

PMID- 19092605
TI  - CM, you, and the comp milieu.

PMID- 19092606
TI  - Double trouble: depression and the injured worker.

PMID- 19092607
TI  - Significance of Propionibacterium acnes-positive samples in spinal
      instrumentation.
AB  - STUDY DESIGN: A retrospective study about Propionibacterium acnes infections
      after Cotrel-Dubousset (CD) instrumentation. OBJECTIVES: To analyze the
      significance of P. acnes-positive deep samples after CD. SUMMARY OF BACKGROUND
      DATA: The diagnosis of spinal infections to P. acnes after CD is difficult.
      METHODS: Patients with revision surgery and at least 1 P. acnes-positive deep
      sample, between 2000 and 2006 were included. Group A had 1 revision surgery and
      group B had 2 successive revision surgeries, with P. acnes-positive deep samples.
      Group A was divided into 2 subgroups according to the peroperative macroscopic
      aspect, subgroup A1 with septic tissues, subgroup A2 without septic tissues. The
      biologic characteristics of the patients and the surgical and medical treatments
      were assessed. RESULTS: Sixty-eight patients were included, 60 in group A (A1 =
      33, A2 = 27) and 8 in group B. Group A: 26 patients had 1 or 2 P. acnes-positive
      samples and 34 had at least 3 P. acnes-positive samples. Histology showed chronic
      inflammatory changes. C-reactive protein value median rate was 42 (A1) and 5 mg/L
      (A2). Twenty-two patients had a complete implant removal (14 with antibiotics, A1
      = 12, A2 = 2). Nine patients had a total implant replacement (7 with
      antibiotics). Twenty-two patients had a partial implant removal (17 with
      antibiotics, A1 = 5, A2 = 12). Seven A1 patients had an irrigation and
      debridement (6 with antibiotics). The evolution was favorable for 28 patients.
      Seven patients had a documented sepsis. Group B: during the first revision, 8
      patients had a partial implant removal (2 with antibiotics); during the second
      revision, all patients received antibiotics 4 of whom had a total implant
      removal. The long-term evolution was favorable for 6 patients. CONCLUSION: P.
      acnes infection of spinal instrumentation is difficult to diagnose. Results of at
      least 4 deep sample cultures, histology, and C-reactive protein values must be
      compared to the peroperative macroscopic aspect.

PMID- 19092608
TI  - Effect of age on the perioperative and radiographic complications of multilevel
      cervicothoracic spinal fusions.
AB  - STUDY DESIGN: Retrospective review. OBJECTIVE: To investigate the effect of age
      on the perioperative and radiographic complications associated with multilevel
      (>or=5) fusion of the cervicothoracic spine. SUMMARY OF BACKGROUND DATA: Although
      the elderly comprise a substantial proportion of patients presenting with complex
      spinal pathology necessitating multilevel procedures across the cervical and
      cervicothoracic spine, the risk of perioperative and radiographic complications
      after these procedures is unknown. METHODS: Between 2000 and 2007, 58 patients 65
      years of age or older at a single institution underwent instrumented
      cervicothoracic spinal fusion of at least 5 levels. Fifty-eight patients under
      the age of 65 from the same time period served as a control group. A
      retrospective review of all hospital records, operative reports, radiographs, and
      clinic notes was conducted. Complications were classified as intraoperative,
      major and minor postoperative, and need for revision surgery. Flexion-extension
      radiographs were examined at discharge, 1.5, 6, 12 months, and then yearly,
      thereafter to evaluate fusion status and instrumentation-related complications.
      RESULTS: Principal diagnoses included spondylostenosis, malignancy, vertebral
      fracture, and osteomyelitis. Both groups were similar in number of levels fused
      (elderly, 6.7 +/- 2.1; control, 6.3 +/- 1.7) and circumferential procedures (27
      vs. 28), respectively. There were no significant differences in operative time,
      blood loss, or length of hospital stay. Rates of intraoperative (5.2% vs. 3.4%),
      major (20.7% vs. 17.2%) and minor postoperative complications (27.6% vs. 22.4%),
      and reoperation (8.6% vs. 8.6%) were similar between the 2 groups. Utilization of
      a combined anterior-posterior fusion was associated with increased perioperative
      complications in the elderly on univariate but not multivariate analyses.
      Radiographic evidence of fusion was also comparable between the 2 groups.
      CONCLUSION: Perioperative complication rates of multilevel (>or=5)
      cervicothoracic spinal fusion in the elderly are high but not significantly
      different from those of younger patients. The use of a circumferential fusion
      procedure may increase the risk of a perioperative complication in older
      patients. Fusion rates are similar between the 2 groups.

PMID- 19092609
TI  - Changes in lumbar muscle activity because of induced muscle pain evaluated by
      muscle functional magnetic resonance imaging.
AB  - STUDY DESIGN: Experimental study of changes in muscle recruitment during trunk
      extension exercise at 40% of the repetition maximum, because of induced muscle
      pain. OBJECTIVE: To investigate the effect of lumbar muscle pain on muscle
      activity of the trunk muscles using muscle functional magnetic resonance imaging.
      SUMMARY OF BACKGROUND DATA: Changed muscle recruitment in patients has an
      important impact on the etiology and recurrence of low back pain. The mechanisms
      of these changes in muscle activity are still poorly understood. An experimental
      study investigating the cause-effect relationship of muscle pain on muscle
      recruitment patterns can help to clarify these mechanisms. METHODS: In 15 healthy
      subjects, the muscle activity of the lumbar multifidus, lumbar erector spinae,
      and psoas muscles was investigated with muscle functional magnetic resonance
      imaging. Measurements at rest and after trunk extension exercise at 40% of
      repetition maximum were performed without and with induced pain. RESULTS: The
      lumbar multifidus and lumbar erector spinae were significantly active during the
      trunk extension exercise, whereas the psoas showed no significant activity. The
      activity of the lumbar multifidus, lumbar erector spinae, and psoas muscles, was
      reduced bilaterally and multilevel during the exercise with unilateral low back
      muscle pain. CONCLUSION: These data demonstrate that unilateral muscle pain can
      cause hypoactivity of muscles during trunk extension at 40% of the repetition
      maximum. The changes were not limited to the side and level of pain. Moreover,
      the inhibition was not limited to the multifidus muscle; also the lumbar erector
      spinae and psoas muscles showed decreased activity during the pain condition.
      Further research has to assess possible compensation mechanisms for this reduced
      activity in other muscles.

PMID- 19092610
TI  - A new concept for making decisions regarding the surgical approach for cervical
      ossification of the posterior longitudinal ligament: the K-line.
AB  - STUDY DESIGN: To report a new index, the K-line, for deciding the surgical
      approach for cervical ossification of the posterior longitudinal ligament (OPLL).
      OBJECTIVE: To analyze the correlation between the K-line-based classification of
      cervical OPLL patients and their surgical outcome. SUMMARY OF BACKGROUND DATA:
      Previous studies showed that kyphotic alignment of the cervical spine and a large
      OPLL are major factors causing poor surgical outcome after laminoplasty for
      cervical OPLL patients. However, no report has evaluated these 2 factors in 1
      parameter. METHODS: The K-line was defined as a line that connects the midpoints
      of the spinal canal at C2 and C7. Twenty-seven patients who had cervical OPLL and
      underwent posterior decompression surgery were classified into 2 groups according
      to their K-line classification. OPLL did not exceed the K-line in the K-line (+)
      group and did exceed it in the K-line (-) group. By intraoperative
      ultrasonography, we evaluated the posterior shift of the spinal cord after the
      posterior decompression procedure. The Japanese Orthopedic Association scores
      before surgery and 1 year after surgery were evaluated, and the recovery rate was
      calculated. RESULTS: Eight patients were classified as K-line (-), and 19
      patients were classified as K-line (+). The mean recovery rate was 13.9% in the K
      line (-) group and 66.0% in the K-line (+) group (P < 0.01). Ultrasonography
      showed that the posterior shift of the spinal cord was insufficient in the K-line
      (-) group. CONCLUSION: The present results demonstrate that a sufficient
      posterior shift of the spinal cord and neurologic improvement will not be
      obtained after posterior decompression surgery in the K-line (-) group. Our new
      index, the K-line, is a simple and practical tool for making decisions regarding
      the surgical approach for cervical OPLL patients.

PMID- 19092611
TI  - Evaluation of reliability of post-tetanic motor-evoked potential monitoring
      during spinal surgery under general anesthesia.
AB  - STUDY DESIGN: A prospective research. OBJECTIVE: Compare the reliability of post
      tetanic motor-evoked potential (p-MEP) monitoring in the detection of motor
      injury during spinal surgery with that of conventional MEP (c-MEP). SUMMARY OF
      BACKGROUND DATA: Myogenic MEPs are sensitive to suppression by anesthetics and
      neuromuscular blockade. Recently, we reported a new technique for MEP recording,
      called "p-MEP" in which MEP amplitude can be enlarged by tetanic stimulation of
      peripheral nerve before transcranial stimulation in comparison with that of c
      MEP. The purpose of this study is to compare the reliability of p-MEP monitoring
      in the detection of motor injury during spinal surgery with that of c-MEP.
      METHODS: Eighty patients undergoing elective spinal surgery were enrolled in the
      study. Both c-MEP and p-MEP monitoring were performed throughout the operation in
      each patient. For recording c-MEPs, transcranial electrical train of five pulses
      stimulation with an interstimulus interval of 2 milliseconds was performed and
      compound muscle action potentials were bilaterally recorded from abductor
      pollicis brevis, abductor hallucis, tibialis anterior, and soleus muscles. For
      recording p-MEPs, tetanic stimulation (50 Hz, 50 mA, 5 sec) was applied to the
      left median nerve and bilateral tibial nerves 1 second before transcranial
      stimulation and compound muscle action potentials were recorded from the same
      muscles. The false positive, false negative, and accuracy of MEP monitoring in
      the detection of change in motor function were compared between p-MEP and c-MEP.
      RESULTS: At the baseline, success rates of baseline c-MEP and p-MEP recording
      were 66.3% (53/80) and 92.5% (74/80), respectively. The false positive, false
      negative, and accuracy of p-MEP monitoring were 0%, 0%, and 100%, respectively,
      whereas c-MEP were 4%, 20%, and 95%, respectively. CONCLUSION: The results
      indicate that p-MEP is a more reliable method to detect changes in motor function
      during spinal surgery under general anesthesia in comparison with c-MEP.

PMID- 19092613
TI  - RhBMP-2 versus iliac crest bone graft for lumbar spine fusion: a randomized,
      controlled trial in patients over sixty years of age.
AB  - STUDY DESIGN: Prospective randomized controlled trial of rhBMP-2/ACS (Infuse bone
      graft) versus iliac crest bone graft (ICBG) for lumbar spine fusion in patients
      over 60 years of age. OBJECTIVE: To report on clinical, radiographic, and
      economic outcomes, at 2-year follow-up, in patients treated by posterolateral
      lumbar fusion with rhBMP-2/ACS versus ICBG. SUMMARY OF BACKGROUND DATA: RhBMP
      2/ACS is widely used "off-label" for posterolateral spinal fusion. Despite
      encouraging initial reports, outstanding issues include the need for evidence
      regarding safety and efficacy in an older population; and an assessment of cost
      effectiveness. METHODS: Patients over 60 years old were randomized to rhBMP-2/ACS
      (n = 50) or ICBG (n = 52). Oswestry Disability Index, Short Form-36, and
      numerical rating scales for back and leg pain were determined preoperatively and
      at 6, 12, and 24 months postoperatively. Fusion was evaluated by fine-cut
      computed tomography scan 2 years postoperatively by 3 reviewers. All in-patient
      and subsequent out-patient event costs were recorded by a dedicated hospital
      coder. RESULTS: Two-year postoperative improvement in Oswestry Disability Index
      averaged 15.8 in the rhBMP-2/ACS group and 13.0 in the ICBG group. Mean
      improvement in Short Form-36 physical component score was 6.6 in the rhBMP-2/ACS
      group and 7.5 in the ICBG group. There were 20 complications in the ICBG group
      and 8 complications in the rhBMP-2/ACS group (P = 0.014). Sixteen ICBG and 10
      rhBMP-2/ACS patients required additional treatment for persistent back or leg
      symptoms. Two rhBMP-2/ACS patients had revision procedures, 1 for nonunion. Eight
      patients in the ICBG group had revision procedures, 5 for nonunion. Mean fusion
      grade on computed tomography scan was significantly (P = 0.030) better in the
      rhBMP-2/ACS (4.3) compared with the ICBG group (3.8). Mean cost of the initial
      admission was $36,530 in the rhBMP-2/ACS group and $34,235 in the iliac crest
      bone graft (ICBG) group. Total cost of care over 2 years was $42,574 for the ICBG
      group and $40,131 for the rhBMP-2/ACS group. CONCLUSION: RhBMP-2/ACS is a viable
      ICBG replacement in older patients in terms of safety, clinical efficacy, and
      cost-effectiveness.

PMID- 19092614
TI  - The safety and efficacy of OP-1 (rhBMP-7) as a replacement for iliac crest
      autograft in posterolateral lumbar arthrodesis: a long-term (>4 years) pivotal
      study.
AB  - STUDY DESIGN: Randomized controlled trial comparing OP-1 (rhBMP-7) with iliac
      crest autograft in patients with symptomatic degenerative spondylolisthesis and
      spinal stenosis treated with decompression and uninstrumented posterolateral
      arthrodesis. OBJECTIVE: To determine the safety and the clinical and radiographic
      efficacy of OP-1 (rhBMP-7) Putty as compared with an iliac crest bone autograft
      control in uninstrumented, single-level posterolateral spinal arthrodesis.
      SUMMARY OF BACKGROUND DATA: Preclinical and preliminary clinical data have
      demonstrated successful fusion and clinical outcomes with the use of OP-1 Putty
      in posterolateral spinal arthrodesis. No prior randomized controlled trial with
      adequate study power has been performed. METHODS: A total of 335 patients were
      randomized in 2:1 fashion to receive either OP-1 Putty or autograft in the
      setting of an uninstrumented posterolateral arthrodesis performed for
      degenerative spondylolisthesis and symptomatic spinal stenosis. Patients were
      observed serially with radiographs, clinical examinations, and appropriate
      clinical indicators, including ODI, Short-Form 36, and visual analog scale
      scores. Serum samples were examined at regular intervals to assess the presence
      of antibodies to OP-1. The primary end point, Overall Success, was analyzed at 24
      months. The study was extended to include additional imaging data and long-term
      clinical follow-up at 36+ months. At the 36+ month time point, CT scans were
      obtained in addition to plain radiographs to evaluate the presence and location
      of new bone formation. Modified Overall Success, including improvements in ODI,
      absence of retreatment, neurologic success, absence of device-related serious
      adverse events, angulation and translation success, and new bone formation by CT
      scan (at 36+ months), was then calculated using the 24-month primary clinical
      endpoints, updated retreatment data, and CT imaging and radiographic end points.
      RESULTS: OP-1 Putty was demonstrated to be statistically equivalent to autograft
      with respect to the primary end point of modified overall success. The use of OP
      1 Putty when compared to autograft was associated with statistically lower
      intraoperative blood loss and shorter operative times. Although patients in the
      OP-1 Putty group demonstrated an early propensity for formation of anti-OP-1
      antibodies, this resolved completely in all patients with no clinical sequelae.
      CONCLUSION: OP-1 Putty is a safe and effective alternative to autograft in the
      setting of uninstrumented posterolateral spinal arthrodesis performed for
      degenerative spondylolisthesis and symptomatic spinal stenosis.

PMID- 19092615
TI  - Effects of clotrimazole on experimental spinal cord ischemia/reperfusion injury
      in rats.
AB  - OBJECTIVE: The effect of clotrimazole was examined using a spinal cord
      ischemia/reperfusion model. METHODS: Twenty albino Wistar rats weighing 234 +/-
      12.3 g were used in this study. Rats were anesthetized intraperitoneally with 50
      mg/kg ketamine HCl. All animals underwent laparotomy under aseptic conditions.
      Abdominal aortas of the animals in all but the sham group were exposed. After
      opening the retroperitoneum, the infrarenal abdominal aorta was clipped for 45
      minutes to produce ischemia/reperfusion injury. Polyethylene glycol (PEG, 1 mL)
      was administrated to the vehicle group. PEG (1 mL) and clotrimazole (30 mg/kg)
      were administered intraperitoneally in the clotrimazole group. Total laminectomy
      of T8-T12 was performed on all rats under a microscope. Spinal cords were excised
      for a length of 2-cm rostrally and 1-cm caudally to the injury site and deep
      frozen at -76 degrees C for biochemical studies. The levels of malondialdehyde,
      glutathione-peroxidase, superoxide dismutase, and catalase were measured as an
      indicator of ischemia level. The most cranial part of the specimens was evaluated
      morphologically. RESULTS: Treatment with clotrimazole significantly decreased
      malondialdehyde, glutathione-peroxidase, superoxide dismutase, and catalase
      levels in comparison with other groups (P = 0.008). Morphologic evaluation
      revealed that clotrimazole protected the axons and their myelin sheaths from
      ischemic damage. CONCLUSION: This study showed the neuroprotective effects of
      clotrimazole on spinal cord ischemia/reperfusion injury.

PMID- 19092616
TI  - Does superior-segment facet violation or laminectomy destabilize the adjacent
      level in lumbar transpedicular fixation? An in vitro human cadaveric assessment.
AB  - STUDY DESIGN: This is an in vitro biomechanical study. OBJECTIVE: The current
      investigation was performed to evaluate adjacent level kinematic change following
      unilateral and bilateral facet violation and laminectomy following 1-, 2-, and 3
      level reconstruction. SUMMARY OF BACKGROUND DATA: The incidence of superior
      segment facet violation with lumbar transpedicular fixation has been reported as
      high as 35%; however, its contribution to biomechanical instability at the
      supradjacent level is unknown. In addition, superior-segment laminectomy has been
      implicated as a risk factor for the development of adjacent level disease. The
      authors assess the acute biomechanical effects of proximal facet violation and
      subsequent laminectomy in an instrumented posterior fusion model in 10 cadaveric
      specimens. METHODS: Biomechanical testing was performed on 10 human cadaveric
      spines under axial rotation (AR), flexion-extension (FE), and lateral bending
      (LB) loading. After intact analysis, pedicle screws were inserted from L5-S1 and
      testing repeated with: (1) preserved L4-L5 facets, (2) unilateral facet breach,
      (3) bilateral breach, and (4) L5 laminectomy. Following biomechanical analysis,
      instrumentation was extended to L4, then L3 and biomechanical testing repeated.
      Full range of motion (ROM) at the proximal adjacent levels were recorded and
      normalized to intact (100%). RESULTS: Supradjacent level ROM was increased for
      all groups under all loading methods relative to intact (P < 0.05). However, AR
      testing revealed progressive instability at the adjacent level in groups 3 and 4,
      relative to group 1, following 1-, 2- and 3-level fixation (P < 0.05). During FE,
      supradjacent level ROM was significantly increased for group 4 specimens compared
      with group 1 after L5-S1 fixation (P < 0.05), and was greater than all other
      groups for L3-S1 constructs (P < 0.05). Interestingly, under lateral bending,
      facet joint destabilization did not change adjacent segment ROM. CONCLUSION:
      There were significant changes in proximal level ROM immediately after posterior
      stabilization. However, an additional increase in supradjacent segment ROM was
      recorded during AR after bilateral facet breach.Subsequent complete laminectomy
      at the uppermostfixation level further destabilized the supradjacent segment in
      FE and AR. Therefore, meticulous preservation of the cephalad-most segment facet
      joints-is paramount to ensure stability.

PMID- 19092618
TI  - Can experimental data in humans verify the finite element-based bone remodeling
      algorithm?
AB  - STUDY DESIGN: A finite element analysis-based bone remodeling study in human was
      conducted in the lumbar spine operated on with pedicle screws. Bone remodeling
      results were compared to prospective experimental bone mineral content data of
      patients operated on with pedicle screws. OBJECTIVE: The validity of 2 bone
      remodeling algorithms was evaluated by comparing against prospective bone mineral
      content measurements. Also, the potential stress shielding effect was examined
      using the 2 bone remodeling algorithms and the experimental bone mineral data.
      SUMMARY OF BACKGROUND DATA: In previous studies, in the human spine, the bone
      remodeling algorithms have neither been evaluated experimentally nor been
      examined by comparing to unsystematic experimental data. METHODS: The site
      specific and nonsite-specific iterative bone remodeling algorithms were applied
      to a finite element model of the lumbar spine operated on with pedicle screws
      between L4 and L5. The stress shielding effect was also examined. The bone
      remodeling results were compared with prospective bone mineral content
      measurements of 4 patients. They were measured after surgery, 3-, 6- and 12
      months postoperatively. RESULTS: After 1 year, there was an average experimental
      bone loss of 9.78% below the positions of pedicle screws, and the results for the
      2 bone remodeling algorithms showed an average bone gain of 8.41% and 1.61%.
      There were no similarities between the bone remodeling and experimental data.
      CONCLUSION: The bone remodeling data showed no resemblances when compared to the
      prospective data of BMC measurements. There was no basis for confirming the
      validity of the bone remodeling algorithms in this study.

PMID- 19092619
TI  - Nonoperative management of type II odontoid fractures in the elderly.
AB  - STUDY DESIGN: Retrospective case series of elderly patients with Type II odontoid
      fractures, with prospective functional follow-up. OBJECTIVE: We aimed to
      investigate the functional outcomes after nonoperative management of Type II
      odontoid fractures in elderly patients at a Level 1 trauma center. SUMMARY OF
      BACKGROUND DATA: Controversy exists regarding the most appropriate method of
      treatment of Type II odontoid fractures in the elderly population. The primary
      aim of management has generally been considered to be the achievement of osseous
      fusion. METHODS: Patients >or=65 years of age presenting to a Level 1 trauma
      center with Type II odontoid fractures were identified retrospectively from a
      prospective neurosurgery database. Those initially treated operatively, or who
      died before follow-up were excluded. Long-term pain and functional outcomes were
      assessed. RESULTS: Forty-two patients were followed up at a median of 24 months
      post injury. Ten patients (24%) were treated in cervical collars alone and 32
      patients (76%) were managed in halothoracic braces. Radiographically demonstrated
      osseous fusion occurred in 50% of patients treated in collars and in 37.5% of
      patients managed in halothoracic bracing. However, fracture stability was
      achieved in 90% and 100% of cases respectively. In patients treated in collars, 1
      patient had severe residual neck pain, severe disability, and poor functional
      outcome. There were no cases of severe pain or disability, or poor functional
      outcome in patients managed in halothoracic orthoses. There was no difference in
      outcome in those achieving osseous union compared with stable fibrous union.
      CONCLUSION: The nonoperative management of Type II odontoid fractures in elderly
      patients results in fracture stability, by either osseous union or fibrous union
      in almost all patients. Long-term clinical and functional outcomes seem to be
      more favorable when fractures have been treated with halothoracic bracing in
      preference to cervical collars. Stable fibrous union may be an adequate aim of
      management in elderly patients.

PMID- 19092620
TI  - Perioperative complications of combined anterior and posterior cervical
      decompression and fusion crossing the cervico-thoracic junction.
AB  - STUDY DESIGN: Retrospective review. OBJECTIVE: To determine the perioperative
      complications for patients undergoing single stage, multilevel, anterior, and
      posterior cervical fusions crossing the cervico-thoracic junction. SUMMARY OF
      BACKGROUND DATA: Cervical spinal stenosis with kyphosis involving 3 or more disc
      levels is often treated via combined anterior decompression and posterior
      instrumented fusion. When long cervical fusions end at C7, many surgeons extend
      the posterior fusion across the cervico-thoracic junction to reduce the potential
      for adjacent segment breakdown. Perioperative complications associated with these
      procedures have not previously been described. METHODS: A retrospective review of
      perioperative complications occurring in patients undergoing combined anterior
      decompression and posterior instrumented arthrodesis crossing the cervico
      thoracic junction. The effect of operative time, blood loss, and fluid
      replacement on the need for extended intubation was tested with a Fisher exact
      test. RESULTS: Thirteen patients fit the inclusion criteria. Nine patients
      experienced at least 1 complication (69%, 9/13) during the perioperative period,
      comprising 16 minor and 5 major complications. The most common complications were
      dysphagia (46%, 6/19) and airway edema requiring extended intubation (38%, 5/13).
      CONCLUSION: Complications are frequent following these procedures, although the
      majority were minor and resolved without lasting effect. Airway edema requiring
      prolonged intubation or reintubation was frequent. With the numbers available, we
      were unable to show a relationship between the need for extended intubation and
      variables including operative time, blood loss, or volume of fluid replacement.

PMID- 19092621
TI  - The repercussions of spinal cord injury on the action of the diaphragmatic crura
      for gastroesophageal reflux containment.
AB  - STUDY DESIGN: Cross-sectional and nonexperimental. OBJECTIVE: To detect and
      compare functional abnormalities in the esophagus and esophagogastric junction in
      2 groups with chronic spinal injuries, 1 with injuries at the phrenic innervation
      level and the other at upper thoracic levels, and to relate these to
      gastroesophageal reflux containment. SUMMARY OF BACKGROUND DATA: There are no
      studies on esophageal manometry with pH metering among spinal cord injury
      patients. Worldwide statistics reveal that the prevalence of gastroesophageal
      reflux disease among spinal cord injury patients is greater than among the
      general population, at around 22% to 27%. The "diaphragmatic crura" has been
      recognized as an important antireflux barrier and should functionally be
      considered to be a muscle separated from the costal diaphragm. However, doubts
      remain regarding whether this difference relates to its innervation. METHODS:
      This was a cross-sectional study on 29 patients with complete spinal cord
      injuries: 14 quadriplegics (level C4) and 15 paraplegics (levels T1-T7).
      Functional abnormalities of the esophagogastric junction, esophagus, and
      diaphragm were investigated using esophageal manometry and diaphragmatic video
      fluoroscopy. Presence of gastroesophageal reflux was investigated subjectively
      (pyrosis and regurgitation) and objectively (pH metering and endoscopy). RESULTS:
      The incidence of gastroesophageal reflux disease was 27.6%, without difference
      between the groups. This became statistically significant when the mean
      diaphragmatic crural pressures were compared (quadriplegics: 37.5 +/- 17.8;
      paraplegics: 26.6 +/- 7.2; P = 0.048). It was also significant in relation to the
      prevalence of at least one of the objective and/or subjective reflux findings
      and/or esophageal peristaltism (quadriplegics: 85.7%; paraplegics: 40.0%; P =
      0.011). CONCLUSION: Spinal injury at the level of the phrenic innervation did not
      predispose the quadriplegics toward greater risk of developing gastroesophageal
      reflux disease. Paradoxically, manometry showed significantly greater crural
      contractility among the quadriplegics.

PMID- 19092622
TI  - The pathogenesis of adolescent idiopathic scoliosis: review of the literature.
AB  - STUDY DESIGN: Review of the literature on the pathogenesis of adolescent
      idiopathic scoliosis (AIS). OBJECTIVE: To discuss the different theories that
      have appeared on this subject. SUMMARY OF BACKGROUND DATA: The pathogenesis of
      AIS, a condition exclusive to humans, has been the subject of many studies. Over
      the years, practically every structure of the body has been mentioned in the
      pathogenesis of AIS; however, the cause of this spinal deformity remains little
      understood. The pathogenesis of this condition is termed multifactorial. METHODS:
      PubMed and Google Scholar electronic databases were searched focused on
      parameters concerning the pathogenesis of adolescent idiopathic scoliosis. The
      search was limited to the English language. RESULTS: No single causative factor
      for the development of idiopathic scoliosis has been identified, it is thus
      termed multifactorial. AIS is a complex genetic disorder. The fully erect
      posture, which is unique to humans, seems to be a prerequisite for the
      development of AIS. CONCLUSION: Although any or all of the mentioned factors in
      this review may play a certain role in the initiation and progression of AIS at a
      certain stage, the presented material suggests that in the observed deformation,
      genetics, and the unique mechanics of the fully upright human spine play a
      decisive role.

PMID- 19092623
TI  - Disc changes in the bridged and adjacent segments after Dynesys dynamic
      stabilization system after two years.
AB  - STUDY DESIGN: Prospective case series. OBJECTIVE: To study the radiologic changes
      in the intervertebral disc after Dynesys dynamic stabilization. SUMMARY OF
      BACKGROUND DATA: Adjacent segment disc degeneration is one of the potential
      complications of fusion surgery. It has been proposed that nonfusion motion
      preservation surgery may prevent accelerated adjacent segment degeneration
      because of the protective effect of persisting segmental motion. METHODS: Thirty
      two patients who underwent Dynesys procedure between November 2002 and June 2004
      and have completed 2-year follow-up MRI scans were included in this study.
      Preoperative and 2 year postoperative lumbar MRI scans were evaluated by 2
      independent observers. T2-weighted mid-sagittal images were used and disc
      degeneration classified according to the Woodend classification of disc
      degeneration. Anterior and posterior intervertebral disc heights were also
      measured. RESULTS: Of the 32 patients, 20 patients underwent Dynesys procedure
      alone and 12 underwent additional fusion at 1 or more levels. A total of 70
      levels were operated on, of which 13 levels were fused.There was a statistically
      significant increase in the mean Woodend score at the operated levels in the
      Dynesys alone group, a change from 1.95 before surgery to 2.52 after surgery (P <
      0.001). The mean Woodend scores changed from 1.27 preoperative to 1.55
      postoperative (P = 0.066) at the proximal adjacent levels, and from 1.37 to 1.62
      at the distal levels (P = 0.157). There was good interobserver agreement
      (weighted kappa score of 0.819). The anterior intervertebral disc height reduced
      by 2 mm from 9.25 to 7.17 (P < 0.001). The posterior disc height increased by
      0.14 mm but this change was not significant. CONCLUSION: Disc degeneration at the
      bridged and adjacent segment seems to continue despite Dynesys dynamic
      stabilization. This continuing degeneration could be due to natural disease
      progression.

PMID- 19092624
TI  - Surgeon practices regarding postoperative thromboembolic prophylaxis after high
      risk spinal surgery.
AB  - STUDY DESIGN: Survey study. OBJECTIVE: To assess a sample of spine surgeons'
      current practices of thromboembolic prophylaxis after high-risk surgery for
      tumors and trauma. SUMMARY OF BACKGROUND DATA: Although chemoprophylaxis for
      thromboembolic events is not routinely used after elective spinal surgery, it is
      more widely recommended in high-risk patients after spine surgery for trauma or
      tumors. In these high-risk cases, surgeons must decide what method(s) of
      prophylaxis to use and when it can be safely initiated. Unfortunately, there are
      limited data evaluating the efficacy or safety of different prophylaxis protocols
      after high-risk spinal surgery; as a result there are no accepted treatment
      guidelines concerning this issue. To the authors' knowledge, no previous study
      examining practices of thromboembolic prophylaxis after high-risk spinal surgery
      has been published. METHODS: One hundred ninety-three orthopaedic and
      neurosurgical spine surgeons with established clinical interest and volume in
      spine trauma and/or spine tumor surgery were invited by email to complete an on
      line questionnaire. Ten questions focused on varying issues that included the
      perceived risk of deep venous thrombosis (DVT), pulmonary embolism (PE),
      postoperative epidural hematoma, preferred chemoprophylactic agents, the safe
      time point for initiation of chemoprophylaxis, and use of inferior vena cava
      (IVC) filters. RESULTS: Ninety-four surgeons completed the questionnaire, which
      represented a 49% response rate. Regarding a safe time point to start
      chemoprophylaxis, the most common response was 48 hours after surgery (21 of 94,
      22%). However, individual responses varied widely: 15% chose 24 hours, 13% chose
      72 hours, 12% chose less than 24 hours, and 10% chose 96 hours. Some indicated
      they would start chemoprophylaxis before surgery, whereas others responded they
      would never use it. Sixty-three percent (59 of 94) stated that they based this
      decision on personal experience over evidence-based review of the literature. A
      majority of surgeons selected low-molecular-weight heparin as their agent of
      choice (54 of 94, 58%). Respondents most commonly (44 of 93, 47%) felt that the
      risk of clinically relevant postoperative epidural hematoma was between 1% and
      5%; 29% (27 of 93) felt the risk was less than 1%; and 17% (16 of 93) felt it was
      as high as 5% to 10%. Those who felt the risk of epidural hematoma to be lower
      than 5% tended to initiate chemoprophylaxis earlier than those who estimated the
      risk to be higher than 5%. Thirty-seven percent (34 of 93) felt the perceived
      risk for a DVT was 1% to 5%; 25% (23 of 94) felt it was 5% to 10%; and 16% (15 of
      93) felt it was less than 1%. Those who estimated the risk of DVT to be higher
      tended to initiate therapy earlier than groups that estimated the risk to be
      lower. Although the decision to use an IVC filter varied considerably, there was
      a clear trend towards having the filter placed before surgery (60 of 78, 77%).
      CONCLUSION: These data are the first to demonstrate the wide variability of
      surgeons' practices regarding thromboembolic prophylaxis in high-risk spine
      surgery patients. This variability is likely a symptom of the glaring paucity of
      scientific evidence concerning the risk for symptomatic epidural hematoma, DVT,
      and PE and the efficacy and safety of specific chemoprophylactic protocols after
      spine surgery. This study highlights the need for more rigorous prospective
      evaluation of thromboembolic risk after spinal surgery and, subsequently, the
      efficacy and safety of currently available thromboembolic prophylaxis protocols.

PMID- 19092626
TI  - After an episode of acute low back pain, recurrence is unpredictable and not as
      common as previously thought.
AB  - STUDY DESIGN: Inception cohort study. OBJECTIVE: To provide the first reliable
      estimate of the 1-year incidence of recurrence in subjects recently recovered
      from acute nonspecific low back pain (LBP) and to determine factors predictive of
      recurrence in 1 year. SUMMARY OF BACKGROUND DATA: Previous studies provide
      potentially flawed estimates of recurrence of LBP because they do not restrict
      the cohort to those who have recovered and are therefore eligible for a
      recurrence. METHODS: We identified 1334 consecutive patients who presented to
      primary care with acute LBP; of these 353 subjects recovered before 6 weeks and
      entered the current study. The primary outcome measure was recurrence of LBP in
      the next year. Specifically, an episode of recurrence was defined in 2 ways:
      recall of recurrence at the 12-month follow-up and report of pain at the 3- or 12
      month follow-up. Risk factors for recurrence were assessed at baseline. Pain
      intensity was assessed at 6 weeks, 3 months, and 12 months and recurrence at 12
      months. Factors that could plausibly affect recurrence were chosen a priori and
      evaluated using a multivariable regression analysis. RESULTS: Recurrence of LBP
      was found to be much less common than previous estimates suggest, ranging from
      24% (95% CI = 20%-28%) using "12-month recall" definition of recurrence, to 33%
      (95% CI = 28%-38%) using "pain at follow-up" definition of recurrence. However,
      only 1 factor, previous episode(s) of LBP, was consistently predictive of
      recurrence within the next 12 months (odds ratio = 1.8-2.0, P = 0.00-0.05).
      CONCLUSION: This study challenges the assumption that the majority of subjects
      will have a recurrence of LBP in a 1-year period. After the resolution of an
      episode of acute LBP, about 25% of subjects will have a recurrence in the next
      year. It is difficult to predict who will have a recurrence within the next year.

PMID- 19092627
TI  - CyberKnife radiosurgery for malignant spinal tumors: characterization of well
      suited patients.
AB  - STUDY DESIGN: A prospective interventional case-series study. OBJECTIVE: To
      provide clinical results of CyberKnife fiducial-free spinal radiosurgery. The
      study focused on patients with no more than 2 malignant spinal tumors. SUMMARY OF
      BACKGROUND DATA: Progress in frameless radiosurgical technology has enabled the
      application of radiosurgery to the spine. The CyberKnife System has been used
      extensively for spine radiosurgery. Until recently, the system required metallic
      fiducial implants for precise target tracking. Fiducial-free spinal radiosurgery
      with the CyberKnife has recently become possible, but until now clinical results
      obtained with this method had been limited. METHODS: From August 2005 until
      October 2007, a consecutive series of 102 patients with a total of 134 malignant
      spinal tumors were selected for single-fraction, fiducial-free CyberKnife
      radiosurgery (CKRS). The study was limited to patients with a maximum of 2
      tumors. Malignant primaries included breast cancer in 23 (22.6%) patients, renal
      cancer in 20 (19.6%) patients, gastro-intestinal cancers in 12 (11.8%) patients,
      prostate cancer each in 12 (11.8%) patients, lung cancer in 9 (8.9%) patients,
      sarcomas in 7 (6.9%) patients. A variety of other malignant tumors were found in
      19 (18.6%) patients. Patients with spinal cord compression or evidence of
      myelopathy were excluded. The sequential neurologic status was recorded. Tumor
      associated spinal pain was prospectively scored according to the visual analogue
      scale (VAS). RESULTS: Of 102 individuals, 22 (21.6%) died due to progression of
      their systemic disease. Mean survival after CKRS was 1.4 years (CI: 1.2-1.6).
      Karnofsky performance score was the only independent predictor of survival after
      radiosurgery on log-rank test (P < 0.0001), and on Cox regression analysis
      (hazard ratio, 0.864, P < 0.0001, CI: 0.809-0.922). Median survival after initial
      tumor diagnosis was 18.4 years (CI: 15.1-23.4). Two (2%) patients suffered
      complications after radiosurgery; a tumor hemorrhage occurred in one, and another
      developed spinal instability. These and 2 other patients were stabilized by
      kyphoplasty. Neurotoxicity or myelopathy was not observed. Local tumor control 15
      months after CKRS was 98% (95% CI: 89-99%). Tumor-associated pain was observed in
      52 (51%) patients. In these patients the median pretreatment pain score of VAS =
      7 (95% CI: 6-7) was significantly reduced to VAS = 1 (95% CI: 4-6) (P < 0.001)
      within 1 week after CKRS. Analysis of variance identified the initial pain score
      as the only significant variable to predict pain reduction after CKRS (P < 0.03).
      Pain recurrence in correlation with tumor recurrence was observed for 3 (6%)
      patients. CONCLUSION: Spinal radiosurgery with the CyberKnife technology is a
      nonivasive, safe, and effective treatment method for patients with 1 or 2 small
      spinal malignant tumors. The best benefit of the treatment can be expected in
      patients with good to excellent clinical condition and patients with severe tumor
      associated pain.

PMID- 19092628
TI  - Long-term intravenous administration of antibiotics for lumbar spinal surgery
      prolongs the duration of hospital stay and time to normalize body temperature
      after surgery.
AB  - STUDY DESIGN: Comparative study of differing durations of antibiotics for spinal
      surgery. OBJECTIVE: To compare rate of infection, duration of hospital stay, days
      until normal body temperature, and a panel of blood tests after surgery between
      long-term and short-term administration of antibiotics for spinal surgery using
      instrumentation. SUMMARY OF BACKGROUND DATA: Recent studies have reported that
      long-term administration of intravenous antibiotics is not necessary to avoid
      superficial and deep infections. We therefore changed the duration of
      administration from 9 to 2 days in our lumbar surgery patients. METHODS: We
      examined 135 patients (average age, 64.9 years) who underwent lumbar spinal
      surgery to insert a pedicle screw system to treat spinal canal stenosis. We
      administered 2 g of cefotiam daily to 60 patients for 9 days after surgery and to
      75 patients for 2 days after surgery. Surgical time, loss of blood, rate of
      infection, duration of hospital stay, days until normal body temperature, and
      data from blood analysis (white blood cell count, and C-reactive protein [CRP]
      level) were statistically compared between the 2 groups. RESULTS: No significant
      differences in intraoperative measures of surgical invasion were observed between
      the 2 groups (surgical time, 209 vs. 220 minutes; blood loss, 530 vs. 576 mL;
      blood transfusion, 344 vs. 380 mL for the long-term and short-term groups,
      respectively). No acute infections occurred in either group. However, the
      duration of hospital stay (20.7 days), time until normal body temperature (5.1
      days), and CRP level (2.23 mg/dL) at day 7 after surgery were significantly less
      in the short-term group than those in the long-term group (27.9 days, 6.8 days,
      and 3.13 mg/dL, respectively; P < 0.05). DISCUSSION: These results indicate that
      short-term intravenous administration of antibiotics did not elevate the
      infection rate after spinal surgery using instrumentation. However, long-term
      administration of antibiotics prolonged the duration of hospital stay, inhibited
      normalization of body temperature, and elevated CRP levels. Long-term
      administration of antibiotics may suppress normal, beneficial bacteria, thereby
      having an adverse effect on patient recovery.

PMID- 19092629
TI  - Face tissue pressure in prone positioning: a comparison of three face pillows
      while in the prone position for spinal surgery.
AB  - STUDY DESIGN: This is a prospective, randomized study. OBJECTIVE: The purpose was
      to compare the tissue-pillow interface pressures at the forehead and chin in
      patients positioned in the prone fashion for spinal surgery on each of 3 facial
      positioners. SUMMARY OF BACKGROUND DATA: Facial pressure ulcers have been
      infrequently observed after spinal surgery requiring prone positioning. This
      requires the use of a specially designed head positioner to maintain spinal
      alignment and to allow space for the endotracheal tube. METHODS: We enrolled 66
      consecutive elective thoracic and/or lumbar surgery patients from 18 to 65 years
      of age. Patients were randomized on entry into the study to 1 of 3 positioners.
      Facial tissue pressures were measured at the patient's forehead and chin at times
      0, 5, 15, and 60 minutes of positioning. The integrity of the patient's skin was
      recorded and classified at the end of surgery. RESULTS: The pressures measured
      for the Dupaco positioner were lower at all time points at both the forehead and
      the chin in comparison with the other 2 positioners (P < 0.05). The ROHO and the
      OSI positioners created similar chin pressures at all time points (P > 0.05). The
      pressures at the forehead for the ROHO positioner were significantly less than
      those for the OSI positioner at all time points (P < 0.05). Ten patients on the
      OSI positioner had pressure ulcers at the end of the procedure. CONCLUSION: The
      Dupaco ProneView Protective Helmet System is superior to both the OSI and the
      ROHO positioners in decreasing forehead and chin tissue interface pressures
      during prone position surgery.

PMID- 19092630
TI  - Synchronous bilateral invasive lobular breast cancer presenting as carcinomatosis
      in a male.
AB  - Invasive lobular breast carcinoma is an exceedingly rare neoplasm in men,
      representing a very small percentage of all male breast cancers. However, it
      should remain on the differential diagnosis in a patient with metastatic
      carcinoma of unknown origin. We report a case of a 58-year-old man who presented
      with increasing abdominal girth and weight loss. A peritoneal biopsy revealed a
      malignant epithelial neoplastic process focally arranged in a single-file
      pattern. There was immunohistochemical reactivity for cytokeratin AE1/AE3. E
      cadherin, cytokeratin 5/6, prostatic-specific antigen, and leukocyte common
      antigen immunostains were negative. Subsequent gastric and right iliac bone
      biopsies revealed a poorly differentiated carcinoma similar in histology and
      immunophenotype to the previous peritoneal biopsy. Upon a more thorough physical
      examination, bilateral breast masses and nipple retraction were noted. Biopsies
      of the masses revealed estrogen receptor-positive, E-cadherin-negative invasive
      lobular carcinomas with similar histology to all the previous biopsies. This case
      is unusual in that it represents the first reported case of lobular carcinoma of
      the male breast presenting as carcinomatosis. The fact that the patient was male
      prolonged the identification of the primary site. Although a rare neoplasm in a
      male, breast cancer should be included in the differential diagnosis of a
      metastatic carcinoma of unknown origin.

PMID- 19092631
TI  - Mucoepidermoid carcinoma of the cervix: another tumor with the t(11;19)
      associated CRTC1-MAML2 gene fusion.
AB  - Mucoepidermoid carcinoma (MEC) of the uterine cervix is a controversial entity.
      By strict morphologic criteria, the tumor has features identical to those of
      salivary gland MEC and is characterized by nests composed of 3 cell types
      (epidermoid, intermediate, and mucin producing) in the absence of overt glandular
      differentiation. Nonetheless, the entity is not recognized in the current World
      Health Organization classification of cervical tumors. Given the morphologic
      similarity between MEC of the cervix and MEC of the salivary glands, we sought to
      determine if MEC of the cervix harbors the t(11;19)(q21;p13) characteristic of
      MEC of the major and minor salivary glands, a rearrangement that results in
      fusion of the cyclic adenosine 3',5' monophosphate coactivator CRTC1 to the Notch
      coactivator MAML2. We identified 7 cervical tumors from our departmental files
      and performed reverse transcription-polymerase chain reaction and fluorescence in
      situ hybridization-based molecular analysis for rearrangements of CRTC1 and
      MAML2; 14 conventional cervical adenosquamous carcinomas were used as controls.
      Analysis of the cervical MECs demonstrated a CRTC1-MAML2 fusion in 1 case,
      rearrangements of CRTC1 in 4 cases, and aberrations of MAML2 in 5 cases
      (rearrangements in 2 cases, amplification in 3 cases). All MEC showed aberrations
      of at least 1 of the loci, whereas none of the cervical adenosquamous carcinomas
      harbored rearrangements or amplification of either locus. Our results demonstrate
      that cervical tumors defined as MEC by strict morphologic criteria harbor genetic
      aberrations involving the genes characteristically rearranged in MEC of the
      salivary glands, and suggest that cervical MEC is an entity distinct from
      conventional cervical adenosquamous carcinoma. The development of drug therapy
      targeted to the genes rearranged in MEC underscores the importance of correct
      classification of cervical MEC because the diagnosis may hold therapeutic
      implications different from other cervical malignancies.

PMID- 19092632
TI  - Primary retroperitoneal mucinous tumors: a clinicopathologic study of 18 cases.
AB  - Primary retroperitoneal mucinous tumors (PRMTs) are uncommon neoplasms occurring
      almost exclusively in women. PRMTs are divided into mucinous cystadenoma (MC),
      mucinous borderline tumors or tumors of low malignant potential (MLMP), and
      mucinous carcinomas (MCas). In this retrospective study, we present the
      clinicopathologic features of 18 such cases, the largest series to date. All
      patients were women, ranging in age from 20 to 63 years (mean 38.6 y). All except
      2 patients presented with an enlarged mass during a routine examination or by
      self-palpation. All tumors were located exclusively in the retroperitoneum, with
      histologic or clinical confirmation of the lack of ovarian involvement. The
      tumors ranged from 7 to 26 cm (mean 13.2 cm). The gross appearance was variable:
      unilocular cyst with a thin wall (4 cases), predominantly cystic with papillary
      areas or nodule(s) (8 cases), multiloculated cyst with or without nodules (1 case
      each), and predominantly solid with cystic areas (4 cases). Histologically, there
      were 2 cases of MC, 7 of MLMP (7 cases; 3 of them with intraepithelial carcinoma
      and 1 with microinvasion), and 9 of MCas (9 cases, 5 of them associated with MLMP
      and 1 associated with MC). Three of the MCas had areas of anaplastic or
      sarcomatoid carcinoma whereas 1 had an associated sarcoma. Immunohistochemical
      studies were performed in 6 cases. Cytokeratin 7 was diffusely positive in all
      cases studied, whereas cytokeratin 20 and cytokeratin 17 were focally positive in
      4 and 2 cases, respectively. All patients underwent surgical resection of the
      entire tumor. Two patients with MCa and sarcoma or sarcomatoid carcinoma received
      chemotherapy. Follow-up was available in 16 cases, ranging from 1 to 148 months
      (mean 40 mo, median 22 mo). Two patients died of disease at 5 and 9 months; both
      had MCa with anaplastic carcinoma or sarcoma. Three patients with MCa were alive
      with disease at 14, 26, and 58 months. The remaining patients were alive with no
      evidence of disease. In this study, MLMP and MCa were more common than MC. PRMTs
      seem to be nonaggressive neoplasms, except in cases containing anaplastic
      carcinoma or sarcoma.

PMID- 19092633
TI  - Isolated solitary ducts (naked ducts) in adipose tissue: a specific but
      underappreciated finding of pancreatic adenocarcinoma and one of the potential
      reasons of understaging and high recurrence rate.
AB  - The distinction of ductal adenocarcinoma from chronic pancreatitis remains one of
      the most difficult challenges in surgical pathology. The glandular units of
      invasive carcinoma are often well formed with well-polarized cells, appearing
      deceptively benign. Conversely, the ducts of chronic pancreatitis may be atypical
      and pseudoinfiltrative as a result of acinar atrophy and fibrosis. We recently
      noted isolated solitary ductal units (ISDs) in adipose tissue to be a reliable
      indicator of adenocarcinoma. In this study, the frequency of ISDs was
      investigated in 105 pancreatic resections with ductal adenocarcinoma and 32 with
      chronic pancreatitis only. ISD was defined as a solitary gland lying individually
      in adipose tissue, either directly abutting adipocytes or separated from them by
      only a thin rim of fibromuscular tissue. ISD was detected in 50/105 (47.6%) of
      pancreatic resections for ductal adenocarcinoma, but not in any resections with
      chronic pancreatitis only (specificity 100%; sensitivity 47.6%). Most of the ISDs
      were very well differentiated and cytologically bland. A small subset of these
      units represented vascular invasion, in which the carcinoma cells epithelialized
      the vessel lining, transforming the vessel into a duct-like structure, virtually
      indistinguishable from normal ducts or PanINs. The vascular nature of these units
      was verified by Elastic-Van Gieson stain and muscular markers highlighting the
      elastic lamina and muscular wall, respectively. ISDs were often located in
      histologic sections taken for the evaluation of the retroperitoneal margin and
      pancreatic-free surfaces where adipose tissue is more abundant. In conclusion,
      ISD lying in adipose tissue unaccompanied by other elements, present in 47.6% of
      pancreatic resections when peripancreatic soft tissues away from the tumor are
      sampled, is a very specific finding for carcinoma that may be instrumental in the
      diagnosis and staging of carcinoma as well as margin evaluation.

PMID- 19092634
TI  - Expression of the urothelial differentiation markers GATA3 and placental S100
      (S100P) in female genital tract transitional cell proliferations.
AB  - The degree of urothelial differentiation in putative transitional (urothelial)
      proliferations in the female genital tract is still controversial. To further
      investigate the similarities (or dissimilarities) between female genital tract
      transitional proliferations and bladder urothelium, we evaluated the expression
      of S100P and GATA3, 2 proteins that we previously found to be strongly expressed
      in bladder urothelial tumors, in 25 benign ovarian Brenner tumors, 19 Walthard
      cell nests (17 tubal and 2 ovarian hilus), 1 mature teratoma with a benign
      urothelial proliferation, 2 proliferating (borderline) ovarian Brenner tumors, 1
      malignant Brenner tumor, and 12 ovarian transitional cell carcinomas (TCC). Each
      lesion was also evaluated for p63 expression by immunohistochemistry.
      Immunostaining was performed on formalin-fixed, paraffin-embedded tissue sections
      using the avidin-biotin-peroxidase complex method. Eighty-eight percent of
      Brenner tumors were positive for S100P, whereas 96% and 100% were positive for
      GATA3 and p63, respectively. One of 2 proliferating Brenner tumors was positive
      for S100P, whereas both cases were positive for GATA3 and p63; the malignant
      Brenner tumor was positive for S100P and p63, but negative for GATA3. Only 17% of
      TCC were positive for S100p, whereas 33% and 50% of TCC were positive for GATA3
      and p63, respectively. Tubal Walthard cell nests were either completely negative
      or showed only scattered positive staining for S100P; in contrast, 89.5% and 100%
      of Walthard nests, including the 2 ovarian cases were positive for GATA3 and p63.
      The teratoma-associated benign urothelial proliferation was also negative for
      S100P, but positive for GATA3 and p63. Although proliferating and malignant
      Brenner tumors may exhibit a more intermediate immunoprofile, expression of
      S100P, GATA3, and p63 by a majority of ovarian Brenner tumors underscores the
      similarity between these neoplasms and urothelial proliferations of bladder
      origin. The indeterminate phenotype seen in Walthard nests and ovarian TCC
      suggests that these proliferations may represent an incomplete or alternate form
      of differentiation.

PMID- 19092635
TI  - Invasive size is an independent predictor of survival in pulmonary
      adenocarcinoma.
AB  - Current classification of pulmonary adenocarcinoma includes noninvasive
      bronchioloalveolar carcinoma, mixed subtype adenocarcinoma, and several patterns
      of invasive carcinoma. The extent of invasion in mixed subtype adenocarcinoma is
      variable, and prior studies suggest that estimates of extent of desmoplasia or
      invasion and gross tumor size are predictors of survival. Pathologic review of
      178 consecutive primary lung adenocarcinoma resections from 1997 to 2000 was
      performed blinded to outcome. Lymph node metastases were not present in
      adenocarcinomas with less then 0.6 cm of invasion. In multivariate analysis and
      in strata adjusted for stage, measurement of linear extent of invasion was
      significantly associated with survival whereas gross size measurement alone was
      not. Significant differences in median survival were observed when patients were
      divided into noninvasive, microinvasive (<0.6 cm invasion), and invasive
      subcategories. In conclusion, among lung adenocarcinomas, histologic assessment
      of invasive growth may provide valuable prognostic information, and tumors with
      invasion under 0.6 cm have a more indolent clinical course after resection.

PMID- 19092636
TI  - Polypoid PEComa in the rectum of a 15-year-old girl: case report and review of
      PEComa in the gastrointestinal tract.
AB  - PEComa of the gastrointestinal tract, composed of perivascular epithelioid cells
      with myomelanocytic differentiation, is rare with previous literature limited to
      16 case reports. There is a marked female preponderance and approximately one
      third of the cases occur in the pediatric age group. We report PEComa with lymph
      node involvement occurring in the rectum of a 15-year-old girl, treated by
      surgical resection and adjuvant chemotherapy. The patient is well at 9 months
      follow-up with neither radiologic nor endoscopic evidence of recurrence. We
      review the differential diagnosis of intestinal PEComa, which includes malignant
      melanoma, epithelioid gastrointestinal stromal tumors, clear cell sarcoma of soft
      parts, alveolar soft part sarcoma, leiomyosarcoma with HMB45 expression, and
      paraganglioma. Immunohistochemistry can rule out many of these morphologically
      similar tumors but differentiation from clear cell sarcoma may require reverse
      transcription-polymerase chain reaction. We discuss the determination of
      pathologic features indicative of malignancy in PEComa, which is complicated in
      the gastrointestinal tract due to the small number of cases, variability of
      pathologic features reported, and inconsistent reporting of outcome. All 4 tumors
      reporting early recurrence or progression were greater than 5 cm in size and had
      areas of coagulative tumor necrosis. In addition, high nuclear grade and
      lymphovascular invasion were seen in 2 of these 4 cases. We propose that a
      minimum dataset for gastrointestinal PEComa should include these features along
      with mitotic count, infiltrative border, and tumor stage analogous to that used
      in colorectal carcinoma.

PMID- 19092638
TI  - Deep vein thrombosis prophylaxis: friend or foe.
AB  - This article reviews certain aspects of venous thromboembolism, a major cause of
      morbidity and mortality among hospitalized patients. Deep vein thrombosis is a
      frequent complication of various surgical procedures. Knowing predisposing
      factors, including hereditary causes, and triggering risk factors will help us
      identify patients with high risk of venous thromboembolism. The prophylaxis
      recommendations by American College of Chest Physicians are made for groups of
      patients, for whom the benefits seem to outweigh the risks. However, those
      readers who want to adopt the American College of Chest Physicians' guidelines in
      their practices are urged to review in detail the pharmacology of the drugs used
      for thromboprophylaxis, relevant clinical studies, and case reports of spinal
      hematoma. Each patient might have different risks for thrombosis or bleeding and
      the potential for adverse consequences due to the prophylaxis. What is best for
      the group (the epidemiologic perspective) is not necessarily what is best for the
      individual patient (the clinical perspective).

PMID- 19092637
TI  - Neurosarcoidosis: clinical features, diagnosis, and management.
AB  - Sarcoidosis is a multisystemic granulomatous disease, which uncommonly affects
      nervous system. However, when present, it may affect both central and peripheral
      nervous systems and potentially mimics other chronic diseases of the nervous
      system. Pathogenesis of neurosarcoidosis remains largely unknown, and its
      diagnosis and management pose serious challenges to clinicians. Early diagnosis
      and aggressive treatment of neurosarcoidosis are necessary to produce
      satisfactory clinical outcomes. This review discusses clinical manifestations,
      current diagnostic studies, and currently available modalities for management of
      neurosarcoidosis.

PMID- 19092639
TI  - Stem cell therapy for the kidney?
AB  - The kidney has a remarkable capacity to regenerate after injury, as it is not a
      terminally differentiated organ. This regenerative potential is somehow
      incomplete, however, and as the insult continues, progressive and irreversible
      scarring results in chronic renal disease. Dialysis and organ transplantation are
      nonspecific and incomplete methods of renal replacement therapy. Stem cells may
      provide a more efficacious method for both prevention and amelioration of renal
      disease of many etiologies. Although many reports have claimed the existence of
      renal-specific stem or progenitor cells isolated and characterized by various
      methods, the results have been diverse and debatable. The bone marrow stem cells
      seem to play a minor role in renal regeneration after acute ischemia in mice
      through transdifferentiation and cell fusion, but their immediate paracrine
      effects result in considerable improvements in renal function. Therefore, as in
      stem cell therapy for the heart, bone marrow-derived stem cells show promise in
      regeneration of the kidney. Although more research is needed in the basic science
      of renal regeneration, clinical research in animals has demonstrated the
      versatility of stem cell therapy. The first phase of clinical trials of bone
      marrow mesenchymal cells in protection against acute kidney injury may begin
      shortly. This will enable further exploration of stem cell therapy in renal
      patients with multiple comorbidities.

PMID- 19092641
TI  - Hydralazine-induced cholestatic hepatitis.
AB  - Hydralazine has been widely used for treating hypertension, particularly in
      patients with renal failure. We report a case on a patient in whom we believe the
      drug was implicated in an otherwise unexplained disturbance of liver function. A
      63-year-old African-American female with medical history of hypertension and end
      stage renal disease (on hemodialysis) was admitted to the hospital with
      epigastric pain and jaundice. The symptoms started about 1 week ago. Initial
      laboratory tests showed abnormal liver enzymes with elevated conjugated bilirubin
      and alkaline phosphatase suggestive of cholestatic jaundice. Amylase and lipase
      were normal. Abdominal ultrasound showed normal caliber common bile duct without
      evidence of obstruction. Abdominal CT scan does not show any evidence of intra-
      or extrahepatic biliary ductal dilatation, and no mass lesions were seen in the
      pancreas. Further blood chemistry showed worsening of liver enzymes and increased
      bilirubin over the next 2-3 days. Magnetic resonance cholangiopancreatography
      failed to show any evidence of intra- or extrahepatic biliary ductal dilatation.
      No other laboratory evidence of cholestatic jaundice was found. Before proceeding
      for invasive diagnostic procedure, that is, endoscopic retrograde
      cholangiopancreatography, the patient's drug history was reviewed. She was on
      hydralazine 75 mg 3 times per day, started 5 months ago. At that time, her liver
      function tests were normal. As we could not find any other cause of cholestatic
      jaundice, we attributed this as a side effect of hydralazine. A trial was given
      by stopping the hydralazine. It was seen that there was significant improvement
      in the liver function enzymes over the next week. Complete clinical and
      biochemical recovery occurred over the next 4 weeks. Liver injury after long-term
      therapy with hydralazine and after short-term therapy with hydralazine (2-10
      days) has been described. Hydralazine-induced hepatotoxicity may manifest as
      hypersensitivity-type injury, mixed hepatocellular injury, acute hepatitis,
      cholestatic jaundice, or centrilobular necrosis. The Hydralazine-induced
      cholestatic liver injury seems to be fully reversible. Complete clinical and
      biochemical recovery occurs after discontinuation of the drug. Also, the
      differential diagnosis of any patient with hepatocellular injury should include
      medications. This will prevent unnecessary diagnostic tests.

PMID- 19092640
TI  - Appetite suppressants, cardiac valve disease and combination pharmacotherapy.
AB  - The prevalence of obesity in the United States is a major health problem
      associated with significant morbidity, mortality, and economic burden. Although
      obesity and drug addiction are typically considered distinct clinical entities,
      both diseases involve dysregulation of biogenic amine neuron systems in the
      brain. Thus, research efforts to develop medications for treating drug addiction
      can contribute insights into the pharmacotherapy for obesity. Here, we review the
      neurochemical mechanisms of selected stimulant medications used in the treatment
      of obesity and issues related to fenfluramine-associated cardiac valvulopathy. In
      particular, we discuss the evidence that cardiac valve disease involves
      activation of mitogenic serotonin 2B (5-HT2B) receptors by norfenfluramine, the
      major metabolite of fenfluramine. Advances in medication discovery suggest that
      novel molecular entities that target 2 different neurochemical mechanisms, that
      is, "combination pharmacotherapy," will yield efficacious antiobesity medications
      with reduced adverse side effects.

PMID- 19092642
TI  - Nicardipine-induced acute hepatitis in an intensive care unit patient.
AB  - Drug-related hepatotoxicity is now the leading cause of acute liver failure in
      the United States, especially among patients who have no prior liver disease.
      Nicardipine is the only IV calcium channel blocker available for the short-term
      treatment of hypertension with a considerably good safety profile. We report a
      case of nicardipine-induced hepatitis. A patient with history of hypertension was
      admitted because of right middle cerebral artery infarction. Computed tomography
      of the brain showed evolving stroke. The patient went for cerebral angiography
      and stent placement, and during the procedure he had cerebral hemorrhage. He was
      transferred to neurosurgery. After surgery, he was started on hypertonic saline,
      mannitol for cerebral edema, and nicardipine drip for blood pressure control. On
      the fourth day after operation, he started to have fever with progressive
      elevation of liver enzymes [Aspartate amino transferase (AST) 450, Alanine amino
      transferase (ALT) 356, and alkaline phosphatase 299]. Serum bilirubin was 0.6. He
      did not receive blood transfusion. No medical history of hepatitis or liver
      disease was reported. Other medications included metoprolol and heparin. White
      blood cell count was 13,000. Chest x-ray did not show evidence of consolidation.
      Urine analysis was unremarkable. Cultures were negative. Acute hepatitis panel
      was negative. Cerebrospinal fluid examination was normal. Liver enzymes were
      trending up gradually with normal protein and bilirubin. Computed tomography of
      the abdomen was unremarkable. The patient's medications were reviewed. It was
      noticed that the patient started to have fever and elevated liver enzymes after
      administration of nicardipine drip. It was postulated that nicardipine may be the
      culprit of acute hepatitis. Nicardipine drip was stopped, and the patient was
      started on labetalol. Fever started to resolve, and liver enzymes started
      trending down toward normal. The patient remained afebrile after that.

PMID- 19092643
TI  - Therapeutic drug monitoring: appropriateness and clinical utility in
      neuropsychiatry practice.
AB  - A retrospective study was conducted to assess the appropriateness of the
      utilization of therapeutic drug monitoring (TDM) services with regards to
      antiepileptic drugs (AEDs) at a tertiary care hospital, and analysis of 5094
      samples of the carbamazepine (CBZ), phenytoin (PHT), valproic acid (VAP), and
      phenobarbitone (PB) was undertaken. Maximum requisitions were received for CBZ
      (54.92%) followed by PHT (27.05%), VAP (14.40%), and PB (3.61%). About 2.12%
      requisitions were received for patients taking unlabeled AEDs. Reasons for TDM
      were routine monitoring (36.3%), adverse drug reactions (ADRs) (17.2%), relapse
      (30.7%), no response (3.35%), and irregular treatment (2.24%) and not mentioned
      (10.5%). Majority of the samples (69%) were drawn for measuring trough levels;
      however, in 22% time of last dose was not mentioned and 9.64% were for peak or
      random levels. In all, 6.9% requisitions for TDM were sent before steady-state
      levels, and in 15.5% duration of therapy was not mentioned. Blood levels within
      therapeutic range were found with CBZ (63%) followed by PB (56.52%), VAP
      (45.99%), and PHT (42.52%). Blood levels were above therapeutic range in 45.69%,
      29%, and 21.73% patients taking VAP, PHT, and PB, respectively. Unsuspected poor
      compliance was uncovered in 11.8%, 41.2%, and 29.3% requisitions sent with ADR,
      relapse, and routine monitoring as reason for drug levels, respectively. Only
      half of all AED measurement requisitions were complete and met the criteria for
      appropriate AED-level determination. Incomplete requisitions lead to difficulty
      in uniform interpretation of results and thus add to unnecessary costs.

PMID- 19092644
TI  - Effect of a combined therapeutic approach of intensive lipid management, omega-3
      fatty acid supplementation, and increased serum 25 (OH) vitamin D on coronary
      calcium scores in asymptomatic adults.
AB  - The impact of intensive lipid management, omega-3 fatty acid, and vitamin D3
      supplementation on atherosclerotic plaque was assessed through serial computed
      tomography coronary calcium scoring (CCS). Low-density lipoprotein cholesterol
      reduction with statin therapy has not been shown to reduce or slow progression of
      serial CCS in several recent studies, casting doubt on the usefulness of this
      approach for tracking atherosclerotic progression. In an open-label study, 45
      male and female subjects with CCS of > or = 50 without symptoms of heart disease
      were treated with statin therapy, niacin, and omega-3 fatty acid supplementation
      to achieve low-density lipoprotein cholesterol and triglycerides < or = 60 mg/dL;
      high-density lipoprotein > or = 60 mg/dL; and vitamin D3 supplementation to
      achieve serum levels of > or = 50 ng/mL 25(OH) vitamin D, in addition to diet
      advice. Lipid profiles of subjects were significantly changed as follows: total
      cholesterol -24%, low-density lipoprotein -41%; triglycerides -42%, high-density
      lipoprotein +19%, and mean serum 25(OH) vitamin D levels +83%. After a mean of 18
      months, 20 subjects experienced decrease in CCS with mean change of -14.5% (range
      0% to -64%); 22 subjects experienced no change or slow annual rate of CCS
      increase of +12% (range 1%-29%). Only 3 subjects experienced annual CCS
      progression exceeding 29% (44%-71%). Despite wide variation in response,
      substantial reduction of CCS was achieved in 44% of subjects and slowed plaque
      growth in 49% of the subjects applying a broad treatment program.

PMID- 19092645
TI  - Significance of central aortic stiffness in cardiovascular disease.
AB  - Cardiovascular health has traditionally been monitored by peripheral measurements
      of brachial blood pressure. Although these measurements have proven to be of good
      diagnostic and prognostic value, novel technology now allows us to non-invasively
      and easily obtain measurements of more central arteries, specifically stiffness
      of the central aorta. The purpose of this review is to analyze the role of
      central aortic stiffness in cardiovascular disease and examine the parameters of
      central aortic stiffness measurement in the clinical setting.

PMID- 19092646
TI  - Nitric oxide and aspirin: a new mediator for an old drug.
AB  - Aspirin is known to cause a multitude of pharmacologic actions through inhibition
      of cyclooxygenase(s) and reduced formation of prostaglandins. Recently, however,
      novel cytoprotective and antioxidant mechanisms of aspirin have been identified
      that are independent of cyclooxygenase inhibition. It was shown that aspirin
      directly stimulates the activity of endothelial nitric oxide (NO) synthase
      without affecting the expression of endothelial NO synthase. Increased NO
      formation was found to underlie aspirin-induced sustained protection of
      endothelial cells from oxidant injury. Downstream targets of NO that mediate
      tissue protection include the stress proteins heme oxygenase-1 (HO-1) and
      ferritin. Both HO-1 and ferritin have been identified as targets of, and
      inducible by, aspirin and, in the case of HO-1, aspirin-triggered lipoxins. It is
      important to note that these effects are specific to aspirin and not induced by
      other nonsteroidal antiinflammatory drugs such as diclofenac, indomethacin, or
      salicylates or by selective cyclooxygenase-2 inhibitors. HO-1 and its antioxidant
      product bilirubin have been reported to be not only involved in vasoprotection,
      but to have a similar function in gastric tissue. Stimulation of NO formation
      through aspirin and ensuing HO-1 induction might therefore help to reduce gastric
      injury or irritation. Moreover, NO functions as a smooth muscle-relaxing agent
      and is thus thought to counteract the reduction in gastric blood flow caused by
      inhibitors of prostaglandin synthesis. It is therefore conceivable that
      activation of these novel antioxidant pathways contributes, at least in part, to
      gastric tolerability and the favorable cardiovascular safety profile of aspirin.

PMID- 19092647
TI  - The utility of omega-3 fatty acids in cardiovascular disease.
AB  - We reviewed the use of marine-derived omega-3 fatty acids in cardiovascular
      disease by discussing key epidemiologic and placebo-controlled studies in people
      with and without prior cardiovascular disease at baseline. In addition, studies
      on the antitriglyceridemic, antihypertensive, hemostatic, antiarrhythmic, and
      antiatherogenic properties of omega-3 fatty acids were examined. Lastly, we
      discussed current dietary and safety recommendations regarding fish and fish oil
      capsules as stated by the US Food and Drug Administration and the US
      Environmental Protection Agency. We found that omega-3 fatty acids have shown to
      significantly reduce coronary mortality and sudden death in people without prior
      cardiovascular disease and reduce all-cause death and cardiac mortality in
      secondary prevention studies. Studies on stroke are still unclear and more
      studies need to focus on stroke subtypes. The beneficial effects of omega-3 fatty
      acids might be the result of their ability to reduce triglyceride levels, blood
      pressure, platelet aggregation, arrhythmia, and atherogenesis. Currently, the
      general public is recommended to consume two fatty fish meals per week (0.3-0.5
      grams per day eicosapentaenoic acid and docosahexaenoic acid). Pregnant mothers
      and children should refrain from eating fish high in methylmercury levels while
      limiting their consumption of other fish varieties to 12 ounces per week.
      Patients with coronary heart disease should have 1 g per day of eicosapentaenoic
      acid and docosahexaenoic acid, whereas patients with hypertriglyceridemia should
      take 3 to 5 g per day of eicosapentaenoic acid and docosahexaenoic acid under a
      physician's supervision.

PMID- 19092648
TI  - Antiplatelet intervention in acute coronary syndrome.
AB  - Clinical trials have demonstrated the usefulness of antiplatelet agents,
      percutaneous coronary intervention, and glycoprotein (GP) IIb/IIIa inhibitors in
      patients with acute coronary syndrome (ACS) based on risk stratification. Studies
      like RITA 3 and FRISC II have shown that an early invasive strategy in high-risk
      patients was associated with lower mortality over the long term compared with
      conservative treatment. High-risk patients with unstable angina/non-ST-elevation
      myocardial infarction derive particular benefit from GP IIb/IIIa inhibitors and
      an early invasive strategy. The TIMI risk score for patients with unstable
      angina/non-ST-elevation myocardial infarction provides an easily implemented tool
      for therapeutic decision-making. Simultaneous assessment of troponin, C-reactive
      protein, and brain natriuretic peptide at the time of presentation of ACS
      provides incremental prognostic information. Recent evidence supports the fact
      that thrombosis and inflammation are interrelated (platelets are involved in
      inflammation and, similarly, leukocytes are involved in hemostasis). The
      platelet, which was once viewed as a bystander in hemostasis, is now recognized
      as a key mediator of thrombosis as well as inflammation. Antithrombotic drugs
      block platelet aggregation and activation at various points in the thrombotic
      cascade and include aspirin, the thienopyridine clopidogrel, and its predecessor
      ticlopidine, intravenous GP IIb/IIIa inhibitors, which block the final common
      pathway of platelet activation and aggregation, unfractionated heparin and low
      molecular-weight heparin, notably enoxaparin, and direct thrombin inhibitors (eg,
      bivalirudin). Bivalirudin has proven noninferior to heparin in patients
      undergoing percutaneous coronary intervention. Enoxaparin is emerging as a safer
      and better alternative to unfractionated heparin in invasively managed patients.
      Declining renal function is a major cause of excess dosing of antithrombotic
      agents and frequently increases the risk of bleeding in elderly patients. Class I
      American College of Cardiology/American Heart Association recommendations for
      acute (<24 hours) management of patients with high-risk non-ST-elevation ACS
      include the use of aspirin, beta-blockers, unfractionated heparin or low
      molecular-weight heparin, or GP IIb/IIIa inhibitors for patients undergoing
      catheterization and revascularization and clopidogrel for patients undergoing
      percutaneous coronary intervention. Medical therapy should be coupled with an
      early invasive strategy of catheterization and revascularization within 48 hours.
      Predischarge initiation of secondary prevention therapies for risk factor
      modification may have substantial advantages for improving the long-term
      prognosis of patients. A large proportion of patients with ACS undergo
      interventional treatment, which underscores the importance of upstream initiation
      of antithrombotic agents. Data from CRUSADE suggests that the majority of
      patients are likely to benefit from aggressive upstream antithrombotic therapy.
      Patients with ACS who have diabetes have a higher risk for recurrent events than
      their nondiabetic counterparts but stand to benefit more from early aggressive
      therapy. Combining GP IIb/IIIa inhibition with drug-eluting stents offers the
      potential to optimize outcomes after revascularization in patients with diabetes.
      Whereas the use of drug-eluting stents has greatly reduced the risk of
      restenosis, patients with diabetes who have ACS and who undergo stenting remain
      at high risk for restenosis and are more likely to require revascularization.
      Increasing adherence to American College of Cardiology/American Heart Association
      guidelines is key to improving outcomes. The optimal management of patients with
      ACS continues to change as new therapies and strategies of care are developed and
      proven effective. The clinical challenge remains to increase physician adherence
      to evidence-based cardiac care for all patients.

PMID- 19092649
TI  - Cardiovascular manifestations of sedatives and analgesics in the critical care
      unit.
AB  - There are numerous sedatives and analgesics used in critical care medicine today;
      these medications are used on critically ill patients, many of whom have heart
      disease, including coronary artery disease or congestive heart failure. The
      purpose of this review is to recognize the effects of these medications on the
      heart. Studies that evaluated the effects of sedatives and analgesics on normal
      individuals or on those with heart disease were reviewed. Current choices for
      sustained sedation in the critically ill include the benzodiazepines, morphine,
      propofol, and etomidate. Each of these medications has their particular
      advantages and disadvantages. Benzodiazepines provide the greatest amnesia and
      cardiovascular safety but they can cause significant hypotension in the
      hemodynamically unstable patient. Morphine provides analgesia and
      cardioprotective activity after ischemia, although the large observational study
      CRUSADE showed increased mortality rate in those patients with non-ST segment
      elevation myocardial infarction who received morphine. Propofol is the most
      easily titratable drug with cardioprotective features, but its use must be
      accompanied with great attention to possible development of propofol infusion
      syndrome, which is a deadly disease, especially in patients with head injury and
      those with septic shock receiving vasopressors. Etomidate has a rapid onset
      effect and short period of action with great hemodynamic stability even in
      patients with shock and hypovolemia, but the incidence of adrenal insufficiency
      during infusion, not bolus doses, may cause deterioration in the circulatory
      stability. In conclusion, the sedatives and analgesics mentioned here have
      characteristics that give them a cardiovascular safety profile useful in
      critically ill patients. However, use of these drugs on an individual basis is
      dependent on each agent's safety and efficacy.

PMID- 19092650
TI  - Switch from conventional to every other day hemodialysis: a comparison pilot
      study.
AB  - Fluid and solute fluctuations during the week are the main drawbacks of
      conventional hemodialysis (cHD) in patients' outcomes. The aim of our study was
      to evaluate the influence of every other day hemodialysis (eodHD) on clinical and
      laboratory parameters and to compare to that of cHD. Eighteen patients on cHD
      were included in the study. Nine patients (group I) were randomly switched to
      eodHD, while the rest (group II) remained on their regular cHD. By the end of the
      study (12 months) we observed a reduction in body weight followed by a parallel
      reduction in predialysis mean blood pressure by 7 mm Hg in group I (p<0.05) and
      the number of antihypertensives. Moreover, a reduction in left ventricular mass
      and an increment of ejection fraction was observed in group I. Hemoglobin levels
      remained stable in both groups, but erythropoietin dose was reduced in eodHD
      group. Dialysis delivered dose (dpKt/V) was higher and urea rebound phenomenon
      was less in group I. Finally, an improvement in uremia related and postdialysis
      symptoms was observed in the same group of patients. Our results showed that
      eodHD improved patients' clinical and biochemical status and therefore might have
      advantages in patients' outcomes compared with cHD.

PMID- 19092651
TI  - Postoperative hemodynamics after cardiopulmonary bypass in survived newborn
      piglets.
AB  - Cardiac function and hemodynamics are frequently decreased during the first hours
      after heart surgery, resulting in inotropic support for treatment and prevention
      of further hemodynamic deterioration. The aim of this study was analysis of
      hemodynamics of neonatal piglets who survived early postoperative course after
      cardiopulmonary bypass (CPB) and cardioplegic arrest without the use of inotropic
      drugs. Newborn piglets (younger than 7 days) were placed on mild hypothermic CPB
      (32 degrees C) for 180 minutes, including 90 minutes of cardioplegic arrest.
      Hemodynamics were examined after termination of CPB and none of the animals
      received any inotropic support. After 6 hours, survived animals were euthanized
      (CPB group, n=4). For control, neonatal piglets were examined for the same time
      interval after surgery without CPB (control group, n=3). Systolic left
      ventricular pressure increased after CPB, mean arterial blood pressure and
      amplitude of left ventricular wall thickness decreased. Compared with control
      group, systolic left-ventricular pressure in CPB group was higher (p<0.05).
      Present data demonstrated hemodynamic depression after cardiac procedures in
      survived neonatal animals. Although the effects may not be solely attributed to
      CPB and myocardial ischemia effects may be potentiate by CPB.

PMID- 19092652
TI  - Cardiac output during high afterload artificial lung attachment.
AB  - Attachment of thoracic artificial lungs (TALs) can increase right ventricular
      (RV) afterload and decrease cardiac output (CO) under certain conditions.
      However, there is no established means of predicting the extent of RV
      dysfunction. The zeroth harmonic impedance modulus, Z0, was thus examined to
      determine its effectiveness at predicting CO during high afterload TAL
      attachment. The MC3 Biolung was attached in four adult sheep groups based on
      baseline (BL) pulmonary vascular resistance and TAL attachment mode: normal,
      parallel (n=7); normal, series (n=7); chronic pulmonary hypertension, parallel
      (n=5), and chronic pulmonary hypertension, series (n=5). The resistance of each
      attachment mode was increased incrementally and instantaneous pulmonary system
      hemodynamic data were acquired at each increment. The change in Z0 from BL,
      DeltaZ0, and percent change in CO (DeltaCO%) were then calculated to determine
      their relationship. The DeltaCO% varied significantly with DeltaZ0 (p<10(-40))
      and DeltaZ02 (p<10(-4)) but not with the attachment and pulmonary hemodynamics
      group. The relationship between the variables for all sheep groups was
      DeltaCO%=0.215DeltaZ0(2)-7.14DeltaZ0+2.94 (R2=0.82) for DeltaZ0 in mm Hg/(L/min).
      Therefore, Z0 is an effective index for determining the CO during TAL attachment
      in both attachment modes with and without elevated pulmonary vascular resistance.

PMID- 19092653
TI  - The impact of pump settings on the quality of pulsatility.
AB  - The study objective was to evaluate the Jostra HL-20 roller pump under different
      baseflow and pump head settings with quantified energy values from pressure and
      flow waveforms, in a simulated pediatric bypass circuit. Pump flow rate was set
      at 800 mL/min for both pulsatile and nonpulsatile perfusion modes and the mean
      arterial pressure (MAP) of the pseudopatient was maintained at 40 mm Hg for each
      experiment. Pulsatile baseflow settings and pump head start points varied with
      each experiment. Pressure and flow waveforms were recorded at preoxygenator,
      precannula, and postcannula sites under each pump setting. A total of 91
      experiments were performed (n=7, nonpulsatile; n=84, pulsatile). Increasing
      baseflow caused decreases in the mean circuit pressure and surplus hemodynamic
      energy (SHE) levels for all pump head start times. When increasing pump head
      start time within each baseflow, values for MAP and SHE increased significantly.
      Regardless of baseflow or pump head start time, values for mean circuit pressure
      and SHE were lower for nonpulsatile flow than for pulsatile flow. Total
      hemodynamic energy values were also significantly higher under pulsatile
      perfusion and increased pump start times while decreasing with increased
      baseflows in the circuit. This study concludes that decreased baseflows with
      increased pump head settings on the Jostra HL-20 roller pump could significantly
      increase quality of generated pulsatile energy. Further research is necessary to
      evaluate these various pump settings under microembolic loads and with different
      circuit components.

PMID- 19092654
TI  - The impact of vacuum-assisted venous drainage and miniaturized bypass circuits on
      blood transfusion in pediatric cardiac surgery.
AB  - Although blood transfusion is essential in pediatric surgery, it is associated
      with increased morbidity. The goal of this study is to assess the efficiency of
      downsized bypass circuits and vacuum-assisted venous return in decreasing the
      need for blood transfusion. This study was performed on 150 patients weighing 2.3
      10 kg. The bypass circuit was composed of a Kids D100 oxygenator and 3/16 in.
      lines, with a 120-ml prime volume. The objective was to maintain a hemoglobin
      level of at least 8 g/dl during the procedure. Venous drainage was both gravity
      dependent and vacuum-assisted. The level and tolerance of hemodilution were
      estimated based on hemoglobin and serum lactate dosages and on the time to
      extubation. Venous drainage varied from 500 to 1200 ml/min. All patients weighing
      <6.4 kg were transfused and 55% of the patients weighing 6.4-10 kg had bloodless
      surgery, none had platelet infusion. In bloodless surgery, the median hemoglobin
      level was 11.4 g/dl before surgery, 8.7 g/dl during bypass, and 10.6 g/dl
      postoperatively, median serum lactate levels were always under 2 mmol/L and the
      median time to extubation was 3 hours. Compared to gravity-dependent venous
      drainage, vacuum-assisted venous return is efficient for further reducing
      allogeneic blood transfusion.

PMID- 19092655
TI  - Optimal expiratory volume profile in tidal liquid ventilation under steady state
      conditions, based on a symmetrical lung model.
AB  - Liquid-assisted ventilation (LAV) using perfluorochemicals (PFC) offers clear
      theoretical advantages over gas ventilation. During tidal liquid ventilation
      (TLV) the residual capacity of the lungs is filled with PFC and a liquid
      ventilator is necessary to inhale and exhale the tidal volume of PFC. However,
      during the expiration phase, a flow limitation (choked flow) can be observed,
      which compromises minute ventilation and consequently the gas exchange. The
      hypothesis of the presented works is that the choked flow can be avoided by
      profiling the expiratory volume. To validate this concept, an elastic symmetrical
      lung numerical model, used to characterize forced expiration in gas ventilation,
      was transposed to TLV. The parameters of the developed numerical model were
      fitted from experimental data obtained on a newborn lamb. The results obtained
      demonstrate that general observations made with gas ventilation still hold,
      however, in TLV: flow limitation in the central airways is the result of a
      coupling between viscous pressure losses and airway compliance, and the flow
      limiting segment is located in the central airways. Using the model results, an
      optimal theoretical expiratory profile seems to be exponential as first
      approximation, and its time constant is dependent on the chocked flow mechanism
      and not on the product of resistance by compliance. This optimal profile is used
      to compute the maximal minute ventilation allowable with an acceptable risk of
      collapse. Also, the sensitivity of minute ventilation to different parameter
      variations were analyzed and practical recommendations are proposed.

PMID- 19092656
TI  - Clot lifespan model analysis of the effects of warfarin on thrombus growth and
      fibrinolysis: role of contact protein and tissue factor initiation.
AB  - Warfarin therapy has served as the backbone of chronic anticoagulation therapy
      for decades to prevent thrombotic morbidity secondary to blood-biomaterial
      interfaces. Unfortunately, thrombotic and bleeding complications are observed
      despite maintenance of therapeutic international normalized ratio (INR) values.
      We proposed to define the effects of warfarin therapy on thrombus growth and
      disintegration following contact pathway protein or tissue factor (TF)
      initiation. Normal subject or patient plasma with INR values between 1.8 and 9.6
      were exposed to TF or celite and tissue-type plasminogen activator (tPA).
      Thrombus growth/disintegration kinetics were determined by changes in resistance
      over time with the clot lifespan model (CSLM), a thrombelastographic-based
      methodology. Data were collected until clot lysis time was observed. Linear
      relationships of the difference between the CLSM parameter values obtained from
      paired celite and TF-activated samples and corresponding INR value were
      determined and reported as r. The time to clot initiation was progressively
      prolonged with increasing INR values in all samples, and speed of clot formation,
      clot strength, and time to onset of fibrinolysis decreased as INR increased.
      Throughout the range of INR values tested, contact activation resulted in faster
      growing, stronger, and longer lived thrombi when compared with matched TF
      activated plasma samples. Only the time to maximum rate of lysis was correlated
      with INR (r=0.36, p=0.005). INR values have little correlation with the
      difference between contact protein and TF-activated coagulation/fibrinolysis.

PMID- 19092657
TI  - Extracorporeal Life Support Registry Report 2008: neonatal and pediatric cardiac
      cases.
AB  - Each year thousands of patients require extracorporeal life support (ECLS) for a
      variety of respiratory, cardiac, and emergency reasons. The ECLS registry, a
      Federal Drug Administration approved control group, provides a database of
      approximately 37,000 ECLS patients from domestic and international hospitals,
      with details about demographic factors, diagnosis, treatment, and complications.
      The report is circulated to Extracorporeal Life Support Organization members with
      the goal of providing feedback on each center's practices relative to the
      performance of all of the centers, and to the general public with the goal of
      enhancing research and improving patient care. In this report, the ECLS Registry
      Report International Summary for July 2008 is analyzed with a specific focus on
      neonatal and pediatric cardiac patients. From the data, it is evident that
      cardiac ECLS patients have a lower chance of survival than respiratory ECLS
      patients, and furthermore, younger patients have a lower chance of survival.
      Requirement for inotropes while on ECLS is by far the most common complication,
      followed by surgical site bleeding, necessitating hemofiltration. The major
      mechanical complications facing cardiac ECLS patients are oxygenator failure and
      clots in the circuit. Databases such as this one provide powerful tools for
      institutions, clinicians, and researchers.

PMID- 19092658
TI  - Plasma exchange during cardiopulmonary bypass in patients with severe hemolysis
      in cardiac surgery.
AB  - Severe mechanical hemolysis after cardiac surgery is a rare occurrence but one of
      the most common complications leading to reoperation. The aim of this study was
      to assess the efficiency and safety of plasma exchange (PE) during
      cardiopulmonary bypass (CPB). Five patients required PE because of severe
      hemolysis after cardiac surgery in Fuwai Hospital from January 2002 to December
      2007: two with periprosthetic leakage and infective endocarditis, one with
      periprosthetic leakage, one with unsatisfied right ventricular outflow tract
      patching, and one with thromboses during extracorporeal membrane oxygenation
      (ECMO). They all needed blood purification to avoid acute renal insufficiency.
      The amount of transfused crystalloid solution, nonprotein colloid, plasma, and
      blood were 1,620+/-906.6 mL, 1,960+/-939.7 mL, 2,240+/-844.4 mL, and 680+/-228.1
      mL. The volume of PE was 3,800+/-1,701.5 mL, and the volume of ultrafiltrate was
      2,470+/-1,327.4 mL. The concentration of free hemoglobin (FHb) before PE, after
      PE, and before discharge were 3,840+/-538 mg/L, 325+/-27 mg/L, and 60.4+/-27
      mg/L, respectively. Five patients were successfully treated with PE during CPB
      without major complications. All patients recovered well. Plasma exchange during
      CPB for severe hemolysis is a safe technique. Acute renal failure induced by
      severe hemolysis can be prevented by PE.

PMID- 19092659
TI  - Failure and off-pump replacement of Incor LVAD system.
AB  - An Incor (Berlin Heart AG, Berlin) left ventricular assist device (LVAD) was
      implanted; 6 months later the patient was admitted to our department for
      intravenous antibiotic therapy for a driveline infection. Two days after
      admission under direct echocardiographic monitoring, the pump failure was noted
      to be entirely dependent on the position of the cable. The pump was successfully
      replaced without cardiopulmonary bypass as a matter of urgency.

PMID- 19092660
TI  - In-vitro localization of initial flow-induced thrombus formation in bileaflet
      mechanical heart valves.
AB  - A major concern with mechanical heart valve prostheses is still the need for
      lifelong anticoagulation to prevent valve thrombosis and thrombembolism.
      Knowledge of the localization of initial thrombus formation on the prosthesis may
      help to improve valve design. Since observation of early clot deposition in vivo
      is difficult, the aim of this study was a detailed assessment of the initial
      stages of thrombus formation at bileaflet mechanical heart valves by means of an
      in-vitro clotting model. Four different bileaflet mechanical heart valves (St.
      Jude Medical, CarboMedics, ATS and On-X) were investigated in a mock circulation
      in aortic position using enzyme-activated milk resembling blood clotting
      potential. Initial development of clot formation on the valves was documented
      photographically and frequency of occurrence was analyzed for both location and
      valve type. For the bileaflet valves, clot depositions could be found in a
      distinct pattern similar in all types. In initial stages, clots developed
      downstream of the leaflets near the orifice ring, 61.5+/-5.8% of which were hinge
      associated, but 38.5+/-5.8% were located isolated laterally and medially remote
      of the hinge region, providing new information on thrombus formation potentially
      useful for improvement of valve design.

PMID- 19092661
TI  - A hemodynamic evaluation of the Levitronix Pedivas centrifugal pump and Jostra Hl
      20 roller pump under pulsatile and nonpulsatile perfusion in an infant CPB model.
AB  - The hemodynamic comparison of the Jostra HL-20 and the Levitronix PediVAS blood
      pumps is the focus this study, where pressure-flow waveforms and hemodynamic
      energy values are analyzed in the confines of a pediatric cardiopulmonary bypass
      circuit.The pseudo pediatric patient was perfused with flow rates between 500 and
      900 ml/min (100 ml/min increments) under pulsatile and nonpulsatile mode. The
      Levitronix continuous flow pump utilized a customized controller to engage in
      pulsatile perfusion with equivalent pulse settings to the Jostra HL-20 roller
      pump. Hemodynamic measurements and waveforms were recorded at the precannula
      location, while the mean arterial pressure was maintained at 40 mm Hg for each
      test. Glycerin water was used as the blood analog circuit perfusate. At each flow
      rate 24 trials were conducted yielding a total of 120 experiments (n=60 pulsatile
      and n=60 nonpulsatile).Under nonpulsatile perfusion the Jostra roller pump
      produced small values for surplus hemodynamic energy (SHE) due to its inherent
      pulsatility, while the Levitronix produced values of essentially zero for SHE.
      When switching to pulsatile perfusion, the SHE levels for both the Jostra and
      Levitronix pump made considerable increases. In comparing the two pumps under
      pulsatile perfusion, the Levitronix PediVAS produced significantly more surplus
      and total hemodynamic energy than did the Jostra roller pump each pump flow
      rate.The study suggests that the Levitronix PediVAS centrifugal pump has the
      capability of achieving quality pulsatile waveforms and delivering more SHE to
      the pseudo patient than the Jostra HL-20 roller pump. Further studies are
      warranted to investigate the Levitronix under bovine blood studies and with
      various pulsatile settings.

PMID- 19092662
TI  - Outcomes using extracorporeal life support for adult respiratory failure due to
      status asthmaticus.
AB  - Our objective was to describe the outcomes for extracorporeal life support (ECLS)
      use in adult respiratory failure because of status asthmaticus and to determine
      whether ECLS use in status asthmaticus is associated with greater survival than
      other indications for ECLS. This retrospective cohort study used the multicenter,
      International ECLS Organization Registry. The study population included 1,257
      adults with respiratory failure requiring ECLS. Status asthmaticus was the
      primary indication for ECLS in 24 patients. A total of 83.3% of asthmatics
      survived to hospital discharge compared with 50.8% of nonasthmatics (n=1,233)
      [odds ratio (OR) favoring survival for asthmatics=4.86, 95% confidence interval
      (CI) 1.65-14.31, p=0.004]. The survival advantage for asthmatics remained
      significant after adjustment for potential confounders. Complications were noted
      in 19 of 24 asthmatics (79.2%). In conclusion, we found that status asthmaticus,
      as an indication for ECLS in adult respiratory failure, seemed to be associated
      with greater survival than other indications for ECLS. However, complications are
      common and whether ECLS confers a survival advantage compared with other salvage
      treatment options remains unknown. More detailed information and complete
      reporting of ECLS use for status asthmaticus are needed to determine whether and
      when the potentially life-saving intervention of ECLS should be initiated in the
      asthmatic failing conventional therapy.

PMID- 19092663
TI  - Severe lactic acidosis treated with prolonged hemodiafiltration in a disseminated
      histoplasmosis.
AB  - Infections with Histoplasma are rarely seen in immunocompromized patients. We
      report the case of a renal transplant recipient who presented with disseminated
      histoplasmosis 3.5 years after transplant. He presented severe lactic acidosis
      (LA), sepsis complicated by circulatory failure, renal failure, and liver
      dysfunction. We describe the successful use of continuous venovenous
      hemodiafiltration (CVVHDF) with regional citrate anticoagulation, treatment that
      stabilized our patient until infectious focus was identified and treated. The
      lactate was decreasing, concomitant with hemodynamic improvement, with reduction
      and suspension of the norepinephrine. The serum lactate level normalized 52 hours
      after CVVHDF initiated (from 28.9 to 2.2 mmol/L). Continuous renal replacement
      therapy was safely applied and can be recommended as an efficient method on
      adjuvant treatment of hyperlactatemia.

PMID- 19092664
TI  - An implementation of sensor-based force feedback in a compact laparoscopic
      surgery robot.
AB  - Despite the rapid progress in the clinical application of laparoscopic surgery
      robots, many shortcomings have not yet been fully overcome, one of which is the
      lack of reliable haptic feedback. This study implemented a force-feedback
      structure in our compact laparoscopic surgery robot. The surgery robot is a
      master-slave configuration robot with 5 DOF (degree of freedom corresponding
      laparoscopic surgical motion. The force-feedback implementation was made in the
      robot with torque sensors and controllers installed in the pitch joint of the
      master and slave robots. A simple dynamic model of action-reaction force in the
      slave robot was used, through which the reflective force was estimated and fed
      back to the master robot. The results showed the system model could be identified
      with significant fidelity and the force feedback at the master robot was
      feasible. However, the qualitative human assessment of the fed-back force showed
      only limited level of object discrimination ability. Further developments are
      underway with this result as a framework.

PMID- 19092666
TI  - Hemodynamic energy delivery of the pulsatile flow in a simulated pediatric
      extracorporeal circuit.
AB  - Objectives of this study were 1) to precisely measure the generation and delivery
      of hemodynamic energy levels during pediatric cardiopulmonary bypass procedure
      using a simulated circuit and 2) to quantify energy losses of the extracorporeal
      circuit components. A conventional roller pump, pediatric hollow-fiber membrane
      oxygenator, arterial filter, arterial cannula, and (1/4)-in tubing were used. The
      circuit was primed with 40/60 glycerin/water mixture. Postcannula (pseudo
      patient's pressure) pressure was maintained 40 mm Hg by a Hoffman clamp. All
      trials were conducted at 800 mL/min of pump flow with pulsatile (n=6) and
      nonpulsatile (n=6) modes at room temperature. Simultaneous blood flow and
      pressures at pre/post oxygenator and pre/post cannula sites were recorded. There
      were gradual decreases in values of circuit mean pressure, energy equivalent
      pressure, surplus hemodynamic energy, and total hemodynamic energy (THE) from pre
      and postoxygenator to pre- and postcannula sites. Approximately 30% of THE
      generated by roller pump was damped by the membrane oxygenator. About 25% of THE
      was lost by the arterial filter and the length of the arterial tubing. Only 15%
      18% of THE was delivered into the pseudo patient. Although the results of this
      study showed that the roller pump could provide higher hemodynamic energy per
      second with pulsatile flow compared with the nonpulsatile flow, the majority
      (80%) of hemodynamic energy was damped by the components of the extracorporeal
      circuit.

PMID- 19092665
TI  - Artificial muscle to wash blood out of fibrillating atrium: an alternative to
      lifelong anticoagulation.
AB  - The Atripump is a motorless, volume displacement pump based on artificial muscle
      technology that could reproduce the pump function of normal atrium. It could help
      prevent blood clots due to blood stagnation and eventually avoid anticoagulation
      therapy in atrial fibrillation (AF). An animal study has been designed to assess
      mechanical effects of this pump on fibrillating atrium. The Atripump is a dome
      shaped silicone coated nitinol actuator. A pacemaker like control unit drives the
      actuator. In five adult sheep, the right atrium (RA) was exposed and dome sutured
      onto the epicardium. Atrial fibrillation was induced using rapid epicardial
      pacing (600 beats/min). Ejection fraction of the RA was obtained with
      intracardiac ultrasound in baseline, AF and Atripump assisted AF conditions. The
      dome's contraction rate was 60/min with power supply of 12V, 400 mA for 200 ms
      and ran for 2 hours in total. Mean temperature on the RA was 39+/-1.5 degrees C.
      Right atrium ejection fraction was 31% in baseline conditions, 5% and 20% in AF
      and assisted AF, respectively. In two animals a thrombus appeared in the right
      appendix and washed out once the pump was turned on. The Atripump washes blood
      out the RA acting as an anticoagulant device. Possible clinical implications in
      patients with chronic AF are prevention of embolism of cardiac origin and
      avoidance of hemorrhagic complication due to chronic anticoagulation.

PMID- 19092667
TI  - In vivo experimental testing of the FW axial blood pump for left ventricular
      support in Fu Wai Hospital.
AB  - A fully implantable, axial flow blood pump has been developed in Fu Wai Hospital
      aiming for clinical use. This ventricular assist device (VAD), which was
      developed after numerous CFD analyses for the flow characteristics of the pump,
      is 58.5-mm long, 30-mm wide (including DC motor), and weighs 240 g. The pump can
      deliver 5 L/min for pressures of 100 mm Hg over 8,000 rpm. In this study, short
      term hemocompatibility effects of the axial left ventricular assist device (LVAD)
      (FW blood pump) were evaluated in four healthy sheep. The device was implanted
      into the left ventricular apex of beating hearts. The outflow graft of each
      device was anastomosed to the descending aorta. The hemolysis, which was
      evaluated in vivo by free hemoglobin value, was below 30 mg/dL. Evaluation of
      serum biochemical data showed that implantation of the FW blood pump in sheep
      with normal hearts did not impair end organ function. Gross and microscopic
      sections of kidney, liver, and lung revealed no evidence of microemboli.
      Performance of the pump in vivo was considered sufficient for a LVAD, although
      further design improvement is necessary in terms of hemolysis and antithrombosis
      to improve biocompatibility of the pump.

PMID- 19092668
TI  - Potential cell sources for tissue engineering of heart valves in comparison with
      human pulmonary valve cells.
AB  - Current techniques to resolve heart valve defects involve the use of prosthetic
      and bioprosthetic materials. These materials lack the potential to grow and are
      not ideal, especially not for pediatric patients. Novel techniques like tissue
      engineering involve the use of biodegradable polymers coated with autologous
      myofibroblast and endothelial cells. We inspected morphological and marker gene
      expression differences between cells harvested from the saphenous vein, or from
      veins and arteries of the umbilical cord, and the cells they are designed to
      replace: the interstitial and endothelial cells of the pulmonary heart valve. We
      assessed the extent to which the endothelial cells from the inspected sources in
      vitro resemble endothelial cells of human pulmonary heart valves, and we found
      that myofibroblast cells, respective of their source, in vitro differ from the
      interstitial cells from human pulmonary heart valves regarding collagen and
      smooth muscle alpha-actin. Therefore we conclude that the cells isolated from the
      saphenous veins, or from veins and arteries of the umbilical cord might be
      feasible cell sources for tissue engineering of heart valve for the pulmonary
      position.

PMID- 19092669
TI  - Microbubble activity in miniaturized and in conventional extracorporeal
      circulation.
AB  - Since the establishment of miniaturized extracorporeal circulation (mECC), there
      has been a great controversy about a possible increased risk of gaseous
      microembolism as compared to conventional extracorporeal circulation (cECC). From
      March 2005 to June 2006, a prospective, randomized study, comparing three
      different mECC (MECC, PRECiSe, Resting Heart) with a cECC (HL30 Maquet) was
      performed. Ninety-three patients undergoing elective bypass surgery were
      included. The amount and size of microbubbles during perfusion was detected in
      the arterial lines utilizing an ultrasound Doppler system. Clinical outcome was
      compared by evaluating the incidence of postoperative neuropsychological
      dysfunction, postoperative renal dysfunction and hospitalization as well as the
      30-day mortality. The highest microbubble activity was measured in all devices
      during the first 10 minutes of extracorporeal circulation. The amount of
      microbubbles was lower in the Resting Heart system (p=0.01), equal in the MECC
      system (p=0.16) and higher using the PRECiSe system as compared to the cECC
      (p=0.002). The microbubble diameter did not differ between all groups (p=0.56).
      Postoperative neuropsychological dysfunction (p=0.45), renal dysfunction
      (p=0.67), days of hospitalization (p=0.27), and 30 day-mortality (p=0.30) did not
      differ between all groups. A great variability in the occurrence of gaseous
      microemboli depending on the applied circuit exists. The Resting Heart system has
      lower, the MECC system an equal and the PRECiSe system depicted a higher activity
      in comparison to a cECC. The hypothesis about an increased risk in mECC in
      comparison to cECC with regard to microbubble activity is not supported by our
      results.

PMID- 19092670
TI  - Hydrodynamic characteristics of porcine aortic valves cross-linked with
      glutaraldehyde and polyepoxy compounds.
AB  - Porcine aortic valve (AoF) tissues cross-linked with glutaraldehyde and epoxy
      compounds were reported to have high anticalcification properties, but their
      hydrodynamic characteristics have not been evaluated. The aim of the present
      study was to investigate the hydrodynamic differences between porcine AoFs, cross
      linked with concomitant use of an epoxy compound and glutaraldehyde, at different
      fixation periods. The valves were mounted on a pulsatile flow circulation
      mimicking a left heart. The left atrial and left ventricular pressures and mitral
      and aortic flows were measured at every 0.002 seconds, and the hydrodynamic
      factor of the valves mounted on the mitral position was estimated. Effective
      orifice area and the regurgitation volume, which are used as indicators of valve
      efficiency, failed to detect significant differences due to glutaraldehyde
      fixation time. In addition, the pressure gradient across the bioprosthetic valve
      and the variation of mitral flow also had no significant differences. The flow
      circuit model of the present study was mimicking of a left heart. The evaluation
      of the mitral valvular function with different glutaraldehyde fixation times was
      accomplished by relating the pressure with the flow, and by estimating the time
      lag between valve motion and transvalvular flow.

PMID- 19092671
TI  - Extracorporeal membrane oxygenation circulatory support after congenital cardiac
      surgery.
AB  - Extracorporeal membrane oxygenation (ECMO) is widely used for circulatory support
      in pediatric cardiac patients with low cardiac output and hypoxemia after cardiac
      surgery. We evaluated retrospectively, the efficacy of postoperative ECMO support
      following congenital cardiac surgery in our hospital. From April 2002 to February
      2008, seven patients (median age 30 months) received postoperative mechanical
      support. Three had complete repair including Fontan circulation and four had
      palliative repair. In four patients, ECMO was initiated in the operating room, in
      three patients in the intensive care unit, postoperatively. Of the seven
      patients, one died on ECMO (support withdrawn), one died shortly after ECMO was
      discontinued, and five were successfully weaned and survived to hospital
      discharge. One of the survivors died 4 months after the operation due to
      pneumonia and septic shock. The mean duration of ECMO support was 121 hours (in
      survivors). During ECMO, the major complication was bleeding, despite adequate
      control of activated clotting time. We conclude that ECMO support for heart
      failure and respiratory insufficiency after congenital cardiac surgery was
      effective, and the result of ECMO support for respiratory insufficiency was
      better than for heart failure.

PMID- 19092672
TI  - Law, liability, and public health emergencies.
AB  - According to many experts, a public health emergency arising from an influenza
      pandemic, bioterrorism attack, or natural disaster is likely to develop in the
      next few years. Meeting the public health and medical response needs created by
      such an emergency will likely involve volunteers, health care professionals,
      public and private hospitals and clinics, vaccine manufacturers, governmental
      authorities, and many others. Conducting response activities in emergency
      circumstances may give rise to numerous issues of liability, and medical
      professionals and other potential responders have expressed concern about
      liability exposure. Providers may face inadequate resources, an insufficient
      number of qualified personnel, overwhelming demand for services, and other
      barriers to providing optimal treatment, which could lead to injury or even death
      in some cases. This article describes the different theories of liability that
      may be used by plaintiffs and the sources of immunity that are available to
      public health emergency responders in the public sector, private sector, and as
      volunteers. It synthesizes the existing immunity landscape and analyzes its gaps.
      Finally, the authors suggest consideration of the option of a comprehensive
      immunity provision that addresses liability protection for all health care
      providers during public health emergencies and that, consequently, assists in
      improving community emergency response efforts.

PMID- 19092673
TI  - Polyps in the gastrointestinal tract: discrepancy between endoscopic forceps
      biopsies and resected specimens.
AB  - BACKGROUND AND AIM: An endoscopic forceps biopsy (EFB) carries the risk of
      missing the neoplastic foci within a polyp as only a small portion of the lesion
      is sampled using this technique. Accordingly, the histological examination of
      specimens obtained by an EFB is of limited accuracy and patient management based
      on the histological findings is controversial. The aim of this prospective study
      was to determine the diagnostic concordance between an EFB and resected tissues
      of gastric and colon polyps. METHODS: Between January 2006 and October 2007, 1312
      gastrointestinal polyps from 896 patients were resected in our hospital. Patients
      with polyps of epithelial origin of at least 8 mm in diameter and not associated
      with polyposis syndromes were included in the study. Polyps of nonepithelial
      origin were excluded. One thousand two hundred and sixty-four polyps of
      epithelial origin [gastric polyps (n=268) and colon polyps (n=996)] obtained from
      813 patients met the inclusion criteria. All patients underwent an EFB and
      resection of the polyp by endoscopic mucosal resection and endoscopic submucosal
      dissection. RESULTS: Multiple polyps existed in 31.6% of the patients. The
      pathological diagnoses of resected gastric polyps were as follows: adenomas with
      low-grade dysplasia, 46 (17.2%); adenomas with high-grade dysplasia, 42 (15.7%);
      hyperplastic polyps, 126 (47.0%); chronic inflammatory polyps, 29 (10.8%); and
      adenocarcinomas, 25 (9.3%). The discrepancy rate between an EFB and the pathology
      of the resected gastric polyps was 39.2% (the Kendall's tau-b and the kappa
      coefficient for agreement between the EFB and resected specimens of gastric
      polyps were 0.577 and 0.472, respectively; P value <0.001). No relationship
      between the size of the gastric polyp and the concordance rate was observed. The
      pathological diagnoses of the resected colon polyps were as follows: adenomas
      with low-grade dysplasia, 559 (56.1%); adenomas with high-grade dysplasia, 229
      (23.0%); hyperplastic polyps, 44 (4.4%); adenocarcinomas, 53 (5.3%); and
      inflammatory polyps, 111 (11.1%). The discrepancy rate between the EFB and the
      pathology of the resected colon polyps was 39.8%. (the Kendall's tau-b and the
      kappa coefficient for agreement between the EFB and the resected specimens of the
      colon polyps were 0.479 and 0.293, respectively; P value <0.001). No relationship
      between the size of the colon polyp and the concordance rate was observed.
      CONCLUSION: Considerable discrepancies were observed in histological findings
      between the EFB and the resected specimens. Therefore, complete removal of the
      entire polyp is recommended to confirm the diagnosis, to remove precancerous
      lesions, and to develop an optimal management plan.

PMID- 19092674
TI  - Fulminant hepatic failure following overdose of the vitamin A metabolite
      acitretin.
AB  - Hepatotoxicity associated with the therapeutic ingestion of the vitamin A
      metabolite acitretin is well recognized. No reported cases of hepatic dysfunction
      as a consequence of acitretin overdose are, however, present. Here for the first
      time we report a case of fulminant hepatic failure following an intentional
      overdose of 600 mg of acitretin. The patient fulfilled the King's College
      Hospital poor prognostic criteria by 66 h after overdose, but demonstrated a
      rapid improvement thereafter and did not require liver transplantation. Given the
      known association between psoriasis and depression, and the possible association
      of acitretin with psychiatric illness, this is an important potential adverse
      event.

PMID- 19092675
TI  - The influence of race and language on chronic hepatitis C virus infection
      management.
AB  - Race, ethnicity and language influence health care delivery and satisfaction with
      treatment in many disease states including chronic hepatitis C virus (HCV)
      infection. In this review, HCV epidemiology and current standard of care is
      reviewed. The influence of race, ethnicity and language on screening, work-up and
      initiation of HCV antiviral treatment is evaluated. Acknowledging that these
      factors do influence health care quality and taking steps to improve
      communication (e.g. translated written documents; use of reliable, trained
      translators in the clinic setting) will facilitate the delivery of an equivalent
      level of care to all patients living with HCV.

PMID- 19092676
TI  - Comparison of propofol and thiopental as anesthetic agents for electroconvulsive
      therapy: a randomized, blinded comparison of seizure duration, stimulus charge,
      clinical effect, and cognitive side effects.
AB  - OBJECTIVES: To compare propofol and thiopental as anesthetic agents for
      electroconvulsive therapy (ECT) with respect to seizure duration, stimulus
      charge, clinical effect, and cognitive side effects. METHODS: Randomized, blinded
      study of 62 depressed patients treated with bilateral ECT. Algorithm-based charge
      dosing was used. RESULTS: The mean seizure duration of the patients in the
      thiopental group was 36.3 seconds versus 25.7 seconds in the propofol group (P =
      0.001). The charge per treatment was 79.5 mC in the thiopental group versus 109.8
      mC in the propofol group (P = 0.026). Sixteen patients in the propofol group
      (52%) reached the highest electrical dose versus 8 patients (26%) in the
      thiopental group (P = 0.014). No difference in response to treatment or number of
      treatments was observed. The mean score on Mini-Mental State Examination (MMSE)
      was 28.9 in the thiopental group versus 26.8 in the propofol group (P = 0.014).
      However, age distribution of patients completing the study differed between the
      groups. CONCLUSIONS: Propofol significantly decreases seizure duration without
      significant difference in the clinical outcome. Using the employed treatment
      algorithm, patients anesthetised with propofol received higher electrical charge.
      Mini-Mental State Examination scores suggest that this results in more severe
      cognitive side effects. Results, however, might be confounded by the differences
      in age distribution in the groups.

PMID- 19092677
TI  - Focal electrically administered therapy: device parameter effects on stimulus
      perception in humans.
AB  - BACKGROUND: Focal electrically administered therapy is a new method of
      transcranial electrical stimulation capable of focal modulation of cerebral
      activity. Other than invasive studies in animals and examination of motor output
      in humans, there are limited possibilities for establishing basic principles
      about how variation in stimulus parameters impact on patterns of intracortical
      stimulation. This study used a simpler paradigm and evaluated the effects of
      different stimulation parameters on subjective perception of the quality and
      location of scalp pain. METHODS: In 2 studies, 19 subjects were randomly
      stimulated over the left forehead, varying the anode-cathode arrangement, the
      intensity of stimulation, the electrode size and placement, and whether the
      current flow was unidirectional or bidirectional. Subjects rated the location of
      the sensation and its quality. RESULTS: The perceived center of stimulation moved
      toward the cathode, regardless of placement. This shift in subjective sensation
      was more prominent when the electricity was unidirectional. In addition, more
      intense stimulation, as well as stimulation with a smaller electrode, caused
      greater perceived pain. Unidirectional stimulation was rated more painful when
      traveling from a large anode to a small cathode and less painful when traveling
      from a small anode to a large cathode. Finally, participants were more likely to
      perceive the electrical stimulation as moving toward a specific direction when
      the intensity was high than when it was low. CONCLUSIONS: The intensity and
      location of sensations can be manipulated by varying the intensity, current
      direction, or geometry of electrodes.

PMID- 19092678
TI  - Cardiac and renal hormones: anticancer effects in vitro and in vivo.
AB  - BACKGROUND: Four cardiovascular hormones, ie, vessel dilator, long-acting
      natriuretic peptide, kaliuretic peptide, and atrial natriuretic peptide each at 1
      mmol/L, decrease up to 97% of human breast, ovarian, pancreatic, colon, kidney,
      and prostate adenocarcinoma cells, as well as small cell and squamous cell lung
      cancer cells within 24 hours. METHODS: Vessel dilator, long-acting natriuretic
      peptide, and kaliuretic peptide were investigated in vivo. RESULTS: These cardiac
      hormones completely stop the growth of human pancreatic adenocarcinomas in
      athymic mice and decrease their tumor volume by 49%, 28%, and 11%, respectively,
      in 1 week. When these cardiac hormones are given subcutaneously for 1 month via
      osmotic pumps with the pumps changed weekly, up to 80% of the human pancreatic
      adenocarcinomas growing in athymic mice can be completely eliminated. Similarly,
      two thirds of human breast cancers in athymic mice can be eliminated without
      surgery with these cardiac hormones. Natriuretic peptide receptors A-, B-, and C-
      are present on the cancer cells to mediate atrial natriuretic peptide's effects.
      CONCLUSIONS: The cardiac hormones' anticancer mechanism of action(s) include a
      strong inhibition of mitogen (epidermal growth factor and insulin) activated
      extracellular signal-regulated kinases (ERK) 1/2 and as well as inhibition of
      basal extracellular-signal regulated kinase 1/2 and upstream MEK 1/2
      phosphorylation. They cause 80% to 90% inhibition of DNA synthesis in the nucleus
      where these cardiac hormones have been demonstrated to localize by
      immunocytochemical techniques.

PMID- 19092679
TI  - Medical student research exposure via a series of modular research programs.
AB  - BACKGROUND: The falling percentage of doctors of medicine applying for National
      Institute of Health-funded research grants is 1 indicator that physician
      scientists are a disappearing breed. This is occurring at a time when increased
      translational, disease-oriented, patient-oriented, and clinical research are
      national goals. One of the keys to providing sufficient numbers of physician
      scientists to support this goal is the active targeting of medical students. We
      hypothesize that an improved research program infrastructure and responsiveness
      to changing student needs will increase student participation in research
      oriented electives. METHODS: We have developed a student research program
      consisting of 2 Students Interested in Research noncredit electives (lecture and
      laboratory based), summer fellowships, support for year-out fellowships, and a
      Distinction in Research program that spans undergraduate medical education.
      Student participation and short-term research outcomes from fall 2004 through
      spring 2008 are analyzed to examine program efficacy. RESULTS: Students involved
      in the early parts of the program initially experienced higher application and
      success rates for summer funding opportunities, but as the program has matured,
      these rates have fallen in line with the class average. Independently, students
      participating in later portions of the program increasingly submit or publish a
      first author paper and have taken a year off for research during medical school.
      Overlap of participation in the programs is generally smaller than expected.
      CONCLUSION: Although structured programs can provide step-wise research
      experiences of increasing intensity, students may not experience a training
      pipeline in which each stage relies on those before and after, and instead may
      sample an a la carte selection of research-based enrichment opportunities.

PMID- 19092680
TI  - Harbingers for Clostridium difficile-associated diarrhea.
AB  - PURPOSE: : Recent research has recognized surrogate markers for Clostridium
      difficile-associated diarrhea (CDAD). Among the most consistently identified
      markers are the leukocyte count, platelet count, and albumin level. Previous
      investigators failed to exclude patients with hematologic disorders that may have
      confounded their results. Therefore, the exclusion of this subset from our study
      lends it a unique perspective. METHODS: : We undertook a retrospective review of
      inpatients at our institution that were diagnosed with nosocomial diarrhea and
      subsequently had a stool sample sent for C. difficile toxins A and B. Patients
      with major hematologic disorders were excluded. RESULTS: : A total of 77 C.
      difficile-positive patients and 91 C. difficile-negative patients were studied.
      Patients with CDAD had a significantly higher leukocyte and platelet count but a
      lower albumin level compared with patients without CDAD. CONCLUSION: : Our
      results support the conclusion of preceding studies that leukocytosis,
      thrombocytosis, and hypoalbuminemia are reliable clinical predictors for CDAD
      even after careful exclusion of confounding factors.

PMID- 19092682
TI  - Validity and reliability of short-term heart-rate variability from the Polar
      S810.
AB  - PURPOSE: : To assess the validity and the reliability of short-term resting heart
      rate variability (HRV) measures obtained using the Polar S810 heart-rate monitor
      and accompanying software. METHODS: : Measures of HRV were obtained from 5-min R
      to R wave (RR) interval data for 19 males and 14 females during 10 min of quiet
      rest on three separate occasions at 1-wk intervals using the Polar S810.
      Criterion measures of HRV were obtained simultaneously using the CardioPerfect
      (CP; Medical Graphics Corporation, St Paul, MN) 12-lead ECG module. Measures of
      validity of the Polar S810 were estimated by regression analysis, and measures of
      reliability of both devices were estimated by analysis of change scores. Measures
      of the SD of normal-to-normal intervals (SDNN), the root mean square of
      successive differences (RMSSD), and the low-frequency (LF) and the high-frequency
      (HF) spectral power and their ratio (LF/HF) were analyzed after log
      transformation, whereas mean RR and LF and HF in normalized units were analyzed
      without transformation. RESULTS: : There were marginal differences between the
      Polar and the CP mean measures of HRV, and the uncertainty in the differences was
      small. The Polar S810 demonstrated high correlations (0.85-0.99) with CP for all
      measures of HRV indicating good to near-perfect validity. Except for the low- and
      the high-frequency normalized units, Polar S810 did not add any substantial
      technical error to the within-subject variability in the repeated measurements of
      HRV. CONCLUSION: : HRV measures obtained with the Polar S810 and accompanying
      software have no appreciable bias or additional random error in comparison with
      criterion measures, but the measures are inherently unreliable over a 1-wk
      interval. Reliability of HRV from longer (e.g., 10 min) and/or consecutive 5-min
      RR recordings needs to be investigated with the Polar and criterion instruments.

PMID- 19092683
TI  - Effect of acute and chronic physical exercise on patients with periodic leg
      movements.
AB  - PURPOSE: Nonpharmacological interventions may lead to an improvement in sleep
      quality. The objective of our study was to evaluate the effects of acute
      intensive exercise and chronic exercise on sleep patterns in patients with
      periodic leg movements (PLM). METHODS: The study involved acute and chronic
      exercise. The acute intensive exercise group consisted of 22 volunteers who
      underwent a maximum effort test and a polysomnography (PSG) on the same night.
      The chronic exercise group included 11 patients who performed 72 physical
      training sessions undergoing three PSG studies on the night of sessions 1, 36,
      and 72. Blood samples were collected from both acute and chronic groups for beta
      endorphin dosage. RESULTS: Our results showed that both forms of physical
      exercise lowered PLM levels. The acute physical exercise increased sleep
      efficiency, rapid eye movement (REM) sleep, and reduced wake after sleep onset,
      whereas the chronic physical exercise increased sleep efficiency, REM sleep, and
      reduced sleep latency. We also found a significant negative correlation between
      beta-endorphin release after acute intensive exercise and PLM levels (r = -0.63).
      CONCLUSION: Physical exercise may improve sleep patterns and reduce PLM levels.
      The correlation between beta-endorphin release after acute intensive exercise and
      PLM levels might be associated with the impact physical exercise has on the
      opiodergic system. We suggest that physical exercise may be a useful
      nonpharmacological treatment for PLM.

PMID- 19092684
TI  - .VO2 response in supramaximal cycling time trial exercise of 750 to 4000 m.
AB  - PURPOSE: Limited research has been done on the .VO2 response to time trial
      exercise in the supramaximal domain or during free range exercise typical of
      competition. The present study was designed to measure and to model the .VO2
      response during supramaximal time trial exercise. METHODS: Well-trained cyclists
      (n = 9) performed a 1-min incremental exercise test to obtain maximal power
      output (P (.VO2max)) and four cycle ergometer time trials of different distances
      (750, 1500, 2500, and 4000 m). Athletes were instructed to finish in as little
      time as possible. .VO2 was measured breath-by-breath and modeled
      monoexponentially over the first 54 s (750 m) or 114 s (1500, 2500, and 4000 m)
      of the time trials. RESULTS: Mean P (.VO2max) in the incremental test was 383 +/-
      28 W. Mean .VO(2max) was 4.5 +/- 0.2 L.min(-1). All time trials were
      characterized by an initial burst in power output during the first 15 s (175 +/-
      23%, 149 +/- 14%, 145 +/- 14%, 139 +/- 10% P (.VO2max) being largest for 750 m.
      Simultaneously, the mean response time was significantly smaller in 750 m
      compared with all other trials (18.8 +/- 2.2, 20.9 +/- 1.9, 20.8 +/- 1.5, and
      21.2 +/- 2.2 s). CONCLUSION: Near maximal values of .VO2 can be reached within 2
      min of strenuous exercise. The larger initial burst in power output in 750 m was
      accompanied by a faster .VO2 response and seems to be of importance to trigger
      the aerobic system maximally.

PMID- 19092685
TI  - Effects of prior heavy exercise on energy supply and 4000-m cycling performance.
AB  - PURPOSE: This study was designed to determine the effects of prior exercise on
      energy supply and performance in a laboratory-based 4000-m time trial. METHODS:
      After one familiarization trial, eight well-trained cyclists (mean +/- SD; age =
      30 +/- 8 yr, body mass = 78.7 +/- 8.6 kg, stature = 181 +/- 5 cm, .VO2 peak =
      63.7 +/- 6.7 mL.kg.(-1)min(-1), peak power output (PPO) = 366 +/- 39 W) performed
      three 4000-m laboratory-based cycling time trials each preceded by one of three
      prior exercise regimens in randomized order: no prior exercise (control), prior
      heavy exercise, and self-selected prior exercise. RESULTS: Cyclists adopted a
      wide range of self-selected prior exercise regimens: duration ranged = 11-80 min,
      intensity = 48-120% PPO, and recovery = 2-11 min. Relative to control, pre-time
      trial blood lactate was raised by 2.5 +/- 1.9 and 1.4 +/- 1.5 mmol.L(-1) after
      prior heavy and self-selected exercise, respectively. The 4000 m was completed
      2.0 +/- 2.3% and 2.2 +/- 1.9% faster after prior heavy and self-selected exercise
      regimens, respectively, and mean power output was 5.4 +/- 3.6% and 6.0 +/- 5.8%
      higher, respectively. The overall aerobic contribution (.VO2) and oxygen deficit
      were not different between conditions (approximately 323 +/- 23 and approximately
      64 +/- 22 mL.kg,(-1) respectively), although .VO2 was higher (P < 0.05) in the
      prior heavy (by 2.1-5.8 mL.kg(-1).min(-1)) and self-selected (2.5-4.3 mL.kg(
      1).min(-1)) regimens compared with the control throughout the first half of the
      time trial. CONCLUSION: Very high intensity cycling performance was improved
      after both self-selected and prior heavy exercise. Such priming increased the
      early aerobic contribution but did not change overall aerobic contribution or
      oxygen deficit. Thus, athletes seem to manage their energy potential to exploit
      the available anaerobic capacity, independent of the aerobic contribution.
      Athletes are advised to perform a bout of heavy exercise as part of their prior
      exercise regimen.

PMID- 19092686
TI  - Control of speed during the double poling technique performed by elite cross
      country skiers.
AB  - PURPOSE: Double poling (DP) as a main technique in cross-country skiing has
      developed substantially over the last 15 yr. The purpose of the present study was
      to analyze the question, "How do modern elite skiers control DP speed?" METHODS:
      Twelve male elite cross-country skiers roller skied using DP at 9, 15, 21, and 27
      km.h(-1) and maximum velocity (V(max)). Cycle characteristics, pole and plantar
      forces, and elbow, hip, and knee joint angles were analyzed. RESULT: Both poling
      frequency and cycle length increased up to 27 km.h (-1)(P < 0.05), with a further
      increase in poling frequency at V(max) (P < 0.05). Peak pole force, rate of force
      development, and rearfoot plantar force increased with submaximal velocities
      (V(sm)), whereas poling time and time-to-peak pole force gradually shortened (P <
      0.05). Changes in elbow joint kinematics during the poling phase were
      characterized by a decreased angle minimum and an increased flexion and extension
      ranges of motion as well as angular velocities across V(sm) (P < 0.05), with no
      further changes at V(max). Hip and knee joint kinematics adapted across V(sm) by
      1) decreasing angles at pole plant and angle minima during the poling phase, 2)
      increasing the ranges of motion and angular velocities during the flexion phases
      occurring around pole plant, and 3) increasing extension ranges of motion and
      angular velocities during the recovery phase (all P values <0.05), with no
      further changes at V(max). CONCLUSIONS: Elite skiers control DP speed by
      increasing both poling frequency and cycle length; the latter is achieved by
      increased pole force despite reduced poling time. Adaptation to higher speeds was
      assisted by an increased range of motion, smaller angle minima, and higher
      angular velocities in the elbow, the hip, and the knee joints.

PMID- 19092687
TI  - Torque interaction among adjacent joints due to the action of biarticular
      muscles.
AB  - In our musculoskeletal system, multiple muscles are involved in the generation of
      torque about a joint. Hence, an infinite number of combinations of muscle
      activities may exist in producing a certain amount of joint torque. Many studies
      have assumed that the level of muscle activity level depends on torque about the
      joint it spans. However, this assumption does not hold true in the presence of
      biarticular muscles. Here we show that the muscle activity level is modulated
      according to a scheme called "cosine tuning" based on our experiment on the
      isometric force exerted by the lower limb, that is, the muscle activity about the
      knee and the hip joints can be represented by a linear summation of the knee and
      hip joint torques. This way of modulation is very simple, but it is unintuitive
      on the point that the activation level of the monoarticular muscles explicitly
      depends on the torque of the adjacent joint that they do not span. It is
      demonstrated that such nontrivial cosine tuning can be mathematically explained
      by assuming that the muscle activity pattern is determined so as to minimize the
      variability of the end point force. Finally, the implications of the cosine
      tuning for muscle strength training and motor control are discussed.

PMID- 19092688
TI  - Paradoxical muscle movement during postural control.
AB  - Undisturbed human standing is primarily characterized by sway of the whole body
      about the ankle joints and is regulated primarily by the calf muscles.
      Traditionally, in accord with normal ideas of postural control, ankle stiffness,
      enhanced by spindle mediated muscle stretch reflexes, has been considered to be
      important for maintaining the upright human stance. This idea predicts that
      during forward sway, the calf muscles are stretched and the mechanoreflex
      response enhances muscle activity to maintain posture and balance. Muscle
      contractile displacement is expected to be positively correlated with bodily
      sway. However, recent experiments have revealed problems with these ideas. Using
      a new ultrasound technique for viewing and measuring the dynamic contractile
      displacements of the calf muscles, it has been shown that calf muscle movement is
      usually poorly or negatively correlated with bodily sway. The shortening of the
      contractile tissue during forward sway and vice versa is described as paradoxical
      muscle movements. This paradoxical muscle movement can be explained by the fact
      that the Achilles tendon, which transmits the calf muscle force, is compliant in
      relation the bodily load. There are two main consequences of the compliant
      Achilles tendon. First, the body is unstable: it cannot be stabilized by
      intrinsic ankle stiffness alone and thus requires modulation of muscle activity
      to maintain balance. Second, contractile displacement is mechanically decoupled
      from bodily sway, which implies that stretch-reflex mechanisms mediated by the
      calf muscle spindles are unable to successfully modulate muscle activity to
      maintain balance. This leaves uncertain the postural role of the numerous calf
      muscle spindles: it is predicted that they signal the effective motor output
      rather than bodily sway.

PMID- 19092689
TI  - Alterations in synergistic muscle activation impact fluctuations in net force.
AB  - Net muscle force recorded during voluntary contractions with multiple agonist
      muscles is the summated result of individual muscle forces. The purpose of this
      article is to synthesize recent findings from several studies on the modulations
      of muscle activity and force fluctuations during steady voluntary contractions
      with multiple agonist muscles in humans. During a sustained low-force contraction
      with the knee extensor muscles, fluctuations in knee extension force changed
      concurrently with the involuntary alternate muscle activity between the rectus
      femoris muscle and the vasti muscles. After prolonged bed rest, the amount of
      change in the fluctuations in net force was associated with the amount of change
      in the EMG distribution among individual muscles within the knee extensor group
      and the ankle extensor group. As an adaptation to bed rest, an increase in the
      fluctuations in plantarflexion force accompanied an increase in the relative
      contribution of the medial gastrocnemius muscle to net force. In contrast, an
      increased contribution of the medial gastrocnemius by an acute increase in muscle
      length reduced force fluctuations. The discrepancy in the changes in force
      fluctuations due to an increased contribution of the medial gastrocnemius between
      two interventions (bed rest and muscle length change) is associated with
      increased low-frequency power in the EMG of the medial gastrocnemius after bed
      rest. In summary, the fluctuations in net force were influenced by the alteration
      in muscle activity among agonist muscles in terms of relative contributions to
      net force and frequency characteristics.

PMID- 19092690
TI  - Force summation between muscles: are muscles independent actuators?
AB  - Muscle force can be transmitted via connective tissues to neighboring muscles.
      The goal of this research is to determine the extent to which this effects force
      summation between synergists during physiological conditions. This manuscript
      reviews two studies examining the interaction between synergists in cat hindlimb.
      Deeply anesthetized cats were mounted in a rigid frame with the foot secured to a
      six-degree-of-freedom load cell coupled to a robotic arm. Muscles were stimulated
      by implanted nerve cuff electrodes. In the first study, force summation was
      measured during isometric contractions. Interactions were studied between the
      lateral gastrocnemius (LG)/soleus (SOL) and the medial gastrocnemius (MG) as well
      as between rectus femoris and vastus lateralis. Invariably, nonlinear force
      summation was less than 10% of maximum force for all three translational
      directions and all three rotational directions. The second study investigated if
      force transmission from SOL fibers was affected by length changes of its two
      joint synergists. Ankle plantar flexor moment, upon activation of only SOL, was
      measured for various knee angles (70 degrees -140 degrees ), which involved
      substantial length changes of LG, MG, and plantaris muscles. Ankle angle was kept
      constant (80 degrees -90 degrees ). SOL ankle moment was not significantly (P =
      0.11) affected by changes in knee angle, neither were the half-relaxation time
      and the maximal rate of relaxation. The connective tissue links between SOL and
      LG were further studied during a tenotomy of the SOL and demonstrated that the
      connective links can transmit approximately 50% of the force from the SOL to the
      LG in nonphysiological conditions. In conclusion, despite strong connective
      tissue linkages, in cat hindlimb synergistic muscles appear to be independent
      actuators if acting in physiological conditions.

PMID- 19092692
TI  - Exercise capacity in the heat is greater in the morning than in the evening in
      man.
AB  - PURPOSE: This study investigated the effect of time of day on endurance exercise
      capacity in a warm environment. METHODS: Nine males cycled to exhaustion at 65%
      .VO2peak in an ambient temperature of 35 degrees C (60% relative humidity) at
      0645 h (AM) and 1845 h (PM). Rectal temperature (Tc), skin temperature (Tsk), and
      heart rate (HR) were recorded and blood and expired air samples collected at rest
      every 5 min during exercise and during recovery. RESULTS: Time to exhaustion was
      longer in the AM trial (45.8 +/- 10.7 min) than in the PM trial (40.5 +/- 9.0
      min; P = 0.009). Resting Tc was lower in the AM trial and remained lower for the
      first 25 min of exercise (P < 0.001). Tc was not different between trials at the
      point of exhaustion (AM = 38.7 +/- 0.9 degrees C, PM = 38.8 +/- 0.6 degrees C; P
      = 0.847). Tsk followed a similar pattern, being lower at rest (P = 0.003) and
      during the initial stages of exercise (P < 0.05) in the AM trial but not
      different at exhaustion (P = 0.896). The rate of rise of Tc tended to be greater
      in the AM trial (P = 0.052), and the rate of rise of Tsk (P = 0.032) and of body
      heat content (P = 0.009) was also greater in the AM trial. HR was initially
      higher in the PM trial, but there was no difference at exhaustion. There were no
      differences between trials in blood glucose concentration or plasma volume
      change. CONCLUSION: The results of this study suggest that endurance exercise
      capacity in the heat was significantly greater in the morning than the evening,
      possibly due to a lower initial Tc.

PMID- 19092694
TI  - Protein modification responds to exercise intensity and antioxidant
      supplementation.
AB  - PURPOSE: To assess the effects of different exercise intensities and antioxidant
      supplementation on plasma protein modification. METHODS: Trained men (n = 41)
      from a homogenous population were randomly assigned to perform cycle ergometer
      exercise either at 70% or 80% of individual .VO2max. Each intensity group was
      randomly assigned to receive either juice powder concentrate (JPC 70%, n = 11;
      JPC 80%, n = 10) or placebo (Plac 70%, n = 10; Plac 80%, n = 10) capsules for 28
      wk. Four controlled exercise bouts and blood collections were conducted at
      baseline and study weeks 4, 16, and 28. Blood samples were drawn before (BE),
      immediately after (IE), and 30 min (30M) and 30 h (30H) postexercise. These
      samples were analyzed to estimate concentrations of carbonyl groups on plasma
      proteins (CP) and the redox state of human serum albumin (HSA). RESULTS: In the
      Plac group, CP concentrations increased at 80% of .VO2max IE and 30M, returning
      to preexercise concentrations by 30H (P < 0.05). At both 16 and 28 wk, the Plac
      groups had significantly higher BE and 30H CP concentrations than the JPC groups
      (P < 0.05). The reduced fraction of HSA, human mercaptalbumin (HMA), decreased at
      all four exercise tests at both exercise intensities IE and 30M, returning to
      preexercise values by 30H (P < 0.05). Supplementation had no influence on HSA.
      CONCLUSIONS: These results indicate that CP concentrations increase with 80%
      .VO2max intensity. The JPC group had lower baseline CP levels after 16 and 28 wk
      and no exercise-induced CP increase. HSA is reversibly shifted to a more oxidized
      state by recent intense exercise.

PMID- 19092693
TI  - Caffeine during exercise in the heat: thermoregulation and fluid-electrolyte
      balance.
AB  - PURPOSE: To investigate the effects of caffeine ingestion on thermoregulation and
      fluid-electrolyte losses during prolonged exercise in the heat. METHODS: Seven
      endurance-trained ( .VO2max = 61 +/- 8 mL.kg.min) heat-acclimated cyclists
      pedaled for 120 min at 63% .VO2max in a hot-dry environment (36 degrees C; 29%
      humidity) on six occasions: 1) without rehydration (NF); 2) rehydrating 97% of
      sweat losses with water (WAT); 3) rehydrating the same volume with a 6%
      carbohydrate-electrolytes solution (CES); or combining these treatments with the
      ingestion of 6 mg caffeine.kg (-1) body weight 45 min before exercise, that is,
      4) C(AFF) + NF; 5) C(AFF) + WAT; and 6) C(AFF) + CES. RESULTS: Without fluid
      replacement (NF and C(AFF) + NF), final rectal temperature (T(REC)) reached 39.4
      +/- 0.1 degrees C, whereas it remained at 38.7 +/- 0.1 degrees C during WAT (CES
      and C(AFF)+ WAT; (P < 0.05). Caffeine did not alter heat production, forearm skin
      blood flow, or sweat rate. However, C(AFF) + CES tended to elevate T(REC) above
      CES alone (38.9 +/- 0.1 degrees C vs 38.6 +/- 0.1 degrees C; P = 0.07). Caffeine
      ingestion increased sweat losses of sodium, chloride, and potassium (
      approximately 14%; P < 0.05) and enlarged urine flow (28%; P < 0.05). CONCLUSION:
      Caffeine ingested alone or in combination with water or a sports drink was not
      thermogenic or impaired heat dissipation. However, C(AFF) + CES tended to have a
      higher T(REC) than CES alone. Caffeine increased urine flow and sweat electrolyte
      excretion, but these effects are not enough to affect dehydration or blood
      electrolyte levels when exercising for 120 min in a hot environment.

PMID- 19092695
TI  - Resistance exercise increases postprandial muscle protein synthesis in humans.
AB  - PURPOSE: We examined the impact of an acute bout of resistance-type exercise on
      mixed muscle protein synthesis in the fed state. METHODS: After a standardized
      breakfast, 10 untrained males completed a single, unilateral lower-limb
      resistance-type exercise session. A primed, continuous infusion of l-[ring
      C6]phenylalanine was combined with muscle biopsy collection from both the
      exercised (Ex) and the nonexercised (NEx) leg to assess the impact of local
      muscle contractions on muscle protein synthesis rates after food intake. Western
      blotting with phosphospecific and pan antibodies was used to determine the
      phosphorylation status of AMP-activated kinase (AMPK), 4E-binding protein (4E
      BP1), mammalian target of rapamycin (mTOR), and p70 ribosomal protein S6 kinase
      (S6K1). RESULTS: Muscle protein synthesis rates were approximately 20% higher in
      Ex compared with NEx (0.098% +/- 0.005% vs 0.083% +/- 0.002%.h, respectively, P <
      0.01). In the fed state, resistance-type exercise did not elevate AMPK
      phosphorylation. However, the phosphorylation status of 4E-BP1 was approximately
      20% lower after cessation of exercise in Ex compared with NEx (P < 0.05).
      Conversely, 4E-BP1 phosphorylation was significantly higher in Ex compared with
      NEx after 6 h of recovery (P < 0.05) with no changes in mTOR phosphorylation. S6
      phosphorylation was greater in Ex versus NEx after cessation of exercise (P <
      0.05), although S6K1 phosphorylation at T was not up-regulated (P > 0.05).
      CONCLUSION: We conclude that resistance-type exercise performed in a fed state
      further elevates postprandial muscle protein synthesis rates, which is
      accompanied by an increase in S6 and 4E-BP1 phosphorylation state.

PMID- 19092696
TI  - Plasma visfatin and ghrelin response to prolonged sculling in competitive male
      rowers.
AB  - PURPOSE: The aim of this investigation was to measure plasma visfatin and ghrelin
      responses to a single endurance rowing training session in male competitive
      single scull rowers. METHODS: Nine national level male rowers (20.1 +/- 1.5 yr;
      183.9 +/- 4.3 cm; 81.0 +/- 5.0 kg; 10.8 +/- 3.3% body fat) completed two trials
      (exercise or control) on separate days. The exercise consisted of a prolonged
      rowing training session lasting approximately 2 h (distance = 20.7 +/- 1.4 km; HR
      = 133 +/- 4 bpm; intensity = 80.2 +/- 1.6% of the HR turn point) followed by a 30
      min rest. Venous blood samples were collected before and after on-water rowing.
      The control trial consisted of rest and blood collection similar to exercise
      trial. RESULTS: No differences were found at baseline values for plasma visfatin,
      ghrelin, and leptin for both trials. The estimated energy expenditure of the
      exercise trial was 1200-1500 kcal. Plasma visfatin (-10.0%; P < 0.05) and leptin
      (-20.0%; P < 0.05) were reduced, and ghrelin concentration was increased (+12.2%;
      P < 0.05) after a 30-min postexercise. No differences in plasma visfatin,
      ghrelin, or leptin over time were observed during control trial. There was no
      relationship between basal visfatin and body composition, energy balance, aerobic
      power, or blood biochemical data. Plasma visfatin (r = -0.76) and ghrelin (r =
      0.75) measured immediately after the training session were related (P < 0.05) to
      the distance covered, and no relation was observed for postexercise leptin (r = 
      0.16; P > 0.05). CONCLUSION: Acute negative energy balance induced by a single
      endurance rowing training session elicited an inverse metabolic response in
      visfatin and ghrelin in competitive male rowers. Our results suggest that
      peripheral markers of negative energy balance, such as visfatin and ghrelin, may
      be regarded as signals for metabolic reaction to the energy cost of acute
      exercise. The results of our study also suggest that an energy-deficit threshold
      must be met for the response to occur.

PMID- 19092697
TI  - Effect of training with different mechanical loadings on MyHC and GLUT4 changes.
AB  - PURPOSE: There is an inverse relationship between insulin sensitivity and
      percentage of myosin heavy chain IIx (MyHC IIx) isoform in sedentary, obese, and
      type 2 diabetic humans. How different exercise conditions may reduce the
      proportion of MyHC IIx and in parallel elevate glucose transporter 4 (GLUT4)
      content is interesting in a therapeutic setting. This study investigates the
      nature of exercise signals regulating MyHC gene switching and whether it is
      accompanied by GLUT4 changes. METHODS: Thirty-two subjects performed high loading
      (60% of 1 repetition maximum [RM]) or low loading (30% of 1 RM) elbow extensions
      in a training apparatus and exercised three times per week for either 5 wk (low
      volume) or 8 wk (high volume). MyHC and GLUT4 contents in the musculus triceps
      brachii were measured by Western blotting pre- and posttraining and after 8 wk of
      detraining. RESULTS: All training regimes resulted in MyHC IIx changes of similar
      magnitude, and differences in training volume had no effect on the outcome. The
      reduction in MyHC IIx content after high loading, high volume was similar to low
      loading, matching volume of training. Thus, there was no effect of training load
      on MyHC changes. GLUT4 increased more after high than low loading (P < 0.0.1). In
      addition, the larger increases in the GLUT4 were associated with the larger
      reductions in MyHC IIx content (r = -0.56, P < 0.01). Detraining returned GLUT4
      to baseline, but MyHC IIx content was still higher than baseline (P < 0.01).
      CONCLUSION: Magnitude of loading is not important for suppression of MyHC IIx but
      for increases in GLUT4 content. The GLUT4 content responded, however, more
      rapidly to detraining than the MyHC IIx and IIa isoforms.

PMID- 19092698
TI  - Mitochondrial haplogroups associated with elite Kenyan athlete status.
AB  - The maternal inheritance of mitochondrial DNA (mtDNA) has enabled construction of
      detailed phylogenies. Analysis of key polymorphisms from these phylogenies allows
      mtDNA to be assigned to haplogroups, which have been associated with elite
      endurance performance. PURPOSE: To compare the frequencies of mtDNA haplogroups
      found in elite Kenyan athletes with those in the general Kenyan population.
      METHODS: DNA samples were obtained from 221 national level Kenyan athletes (N),
      70 international Kenyan athletes (I), and 85 members of the general Kenyan
      population (C). mtDNA haplogroups were classified by sequencing 340 bases of
      hypervariable section (HVS I) and by genotyping known restriction sites.
      Frequency differences between groups were assessed using exact tests of
      population differentiation. RESULTS: The haplogroup distribution of national (P =
      0.023) and international athletes (P < 0.001) differed significantly from
      controls, with international athletes showing a greater proportion of L0
      haplogroups (C = 15%, N = 18%, I = 30%) and lower proportion of L3* haplogroups
      (C = 48%, N = 36%, I = 26%). Although a high number of international athletes
      originated from the Rift Valley province relative to controls (C = 20%, N = 65%,
      I = 81%), subjects from this province did not differ in haplogroup distribution
      from other regions (P = 0.23). Nor did Bantu subjects differ from Nilotic (P =
      0.12) despite an overrepresentation of Nilotic languages among the athletes.
      CONCLUSIONS: International athletes differed in their mtDNA haplogroup
      distribution relative to the general Kenyan population. They displayed an excess
      of L0 haplogroups and a dearth of L3* haplogroups. These findings suggest that
      mtDNA haplogroups are influential in elite Kenyan distance running, although
      population stratification cannot be ruled out.

PMID- 19092699
TI  - Exercise affects platelet-impeded antitumor cytotoxicity of natural killer cell.
AB  - PURPOSE: Natural killer cells (NK) induce the death of tumor cells by
      perforin/granzyme-mediated cytotoxicity, whereas platelets reduce the capacity of
      NK to destroy tumor cells. Physical exercise affects both immune function and
      platelet activity because responses depend on type, intensity, and duration of
      exercise. This investigation explores how various exercise regimens influence
      platelet-impeded cytotoxicity of NK to nasopharyngeal carcinoma cells (NPC).
      METHODS: Thirty sedentary men performed on three occasions moderate exercise (60%
      .VO2max for 40 min), severe exercise (up to .VO2max), and severe exercise after
      warm-up exercise (60% .VO2max for 20 min). NK count and perforin/granzyme B
      contents, NK-NPC binding, and NK-induced NPC apoptosis were measured using a flow
      cytometer, whereas NK-induced NPC detachment from collagen-coated surface was
      determined using an electrical cell-substrate impedance sensing. RESULTS: Severe
      exercise enhanced NK-induced NPC caspase-3 activation, phosphatidylserine (PS)
      exposure, DNA fragmentation, and detachment and was accompanied by increased NK
      count and perforin/granzyme B contents (P < 0.05). Moreover, severe exercise
      simultaneously promoted the suppression of platelet to NK-NPC binding and NK
      induced NPC caspase-3 and -8 activations, PS exposure, DNA fragmentation, and
      detachment (P < 0.05). However, warm-up exercise pretreatment diminished the
      effects of severe exercise in platelet-impeded NK-NPC binding and NK-induced NPC
      apoptosis. Although moderate exercise also suppressed platelet-impeded NK-NPC
      interaction (P < 0.05), no significant changes occurred in NK count and
      perforin/granzyme B contents after this exercise. CONCLUSIONS: Severe exercise
      enhances the cytotoxicity of NK to NPC and simultaneously promotes the platelet
      impeded apoptosis of NPC induced by NK. However, warm-up exercise reduces the
      resistance of platelet to NK-NPC interaction, increasing the efficiency of anti
      NPC cytotoxicity by NK after severe exercise.

PMID- 19092700
TI  - Reliability of RT3 accelerometers among overweight and obese adults.
AB  - PURPOSE: Accurate and reliable measurement of physical activity plays an
      important role in assessing effective lifestyle interventions for obesity. This
      study examined reliability of accelerometer-based estimates of physical activity
      levels of overweight and obese adults before and after a lifestyle weight loss
      program. METHODS: Participants were overweight and obese (body mass index = 25-45
      kg x m) members (n = 1592; 67% female, 42% African American) of the multicenter
      weight loss maintenance trial. They wore RT3 accelerometers during waking hours
      for 7 d at baseline and after a 6-month weight loss intervention that included
      diet and physical activity recommendations. Moderate-to-vigorous physical
      activity (MVPA) and MVPA occurring in bouts >or=10 min (bout MVPA) were assessed.
      RESULTS: At baseline, wear time minimums of 10 and 6 h.d resulted in similar
      average minutes per day of MVPA (18.3 and 18.0 min) and MVPA bout minutes per day
      (6.9 and 6.7 min). Similar wear times occurred after the weight loss intervention
      for MVPA (27.0 and 26.8 min) and bout MVPA (15.1 and 15.0 min). Reliability
      measurements by intraclass correlation (ICC) were larger for 4 versus 2 d x wk
      minimum wear time for both MVPA and bout MVPA (4-d ICC = 0.27-0.44 and 2-d ICC =
      0.19-0.38), but there was little increase in ICC comparing 4 (ICC = 0.27-0.44)
      and 7 d x wk (ICC = 0.30-0.46). CONCLUSIONS: Longer wear time requirements did
      not result in significant increases in reliability. Using 4 d of data with >or=6
      h x d of wear time optimized the balance between ICC and participant burden in
      overweight and obese adults before and after a weight loss intervention. Future
      investigations using accelerometers to estimate MVPA in overweight and obese
      samples can consider requiring less monitor wear time.

PMID- 19092701
TI  - Physical activity and motor skills in children with and without visual
      impairments.
AB  - PURPOSE: To examine the physical activity levels of children with and without
      visual impairments (VI). We further investigated 1) whether degree of VI was
      associated with activity level, 2) whether body composition was associated with
      activity level, and 3) whether interrelationships existed between activity level
      and motor skill performance. METHODS: Ninety-six children with and without VI,
      ages 6 to 12 yr, attending mainstream schools participated. Physical activity was
      assessed by the GT1M accelerometer and motor skill performance by the Test of
      Gross Motor Development-2. Body composition was also determined. RESULTS: Total
      activity [counts per minute (cpm)] was significantly higher in children without
      VI than in children with VI, 578.1 versus 473.2 cpm. Time spent in sedentary and
      light behaviors averaged 81.4% and 15.9% in the children with VI and 78.1% and
      18.6% in the children without VI, with significant between-group differences.
      Participation in moderate-to-vigorous physical activity (MVPA) was significantly
      higher in children without VI versus children with VI. Degree of VI, body mass
      index (BMI), and percent body fat were correlated with time spent in sedentary
      and light activity in children with VI. Time spent in sedentary activity was
      inversely correlated with locomotor and object control scores in children with
      VI. Light activity was positively associated with locomotor scores; total
      activity and MVPA were positively associated with object control scores. For
      children without VI, total activity and time spent in MVPA were positively
      associated with locomotor scores, and time spent in sedentary activity inversely
      associated with object control scores. CONCLUSIONS: The present results emphasize
      the importance of promoting an active lifestyle in children. Special attention
      has to be paid to children with lower visual acuities and children with higher
      BMI.

PMID- 19092702
TI  - Longitudinal study of physical activity and inactivity in preschoolers: the FLAME
      study.
AB  - PURPOSE: To investigate patterns of activity and inactivity in a birth cohort of
      children followed from 3 to 5 yr and to investigate whether changes in activity
      occurred over time. METHODS: Two hundred and forty-four children (44% female)
      were seen annually at 3, 4, and 5 yr. Physical activity and inactivity was
      measured by questionnaire (parent-proxy) and by Actical accelerometers for five
      consecutive days (24-h monitoring) each year in children and once in each parent
      for 7 d (69% with data). RESULTS: Retention of participants was high (92%).
      Viable accelerometry data were obtained for 76-85% of children at each age.
      Reliability estimates ranged from 0.80 (3 yr) to 0.84 (5 yr). Day of the week,
      season, sex, hours of childcare, or birth order did not affect daily average
      accelerometry counts (AAC) at any age. Parental activity correlated weakly with
      the child's activity at 3 and 4 yr (r values = 0.17-0.28), but only the father's
      activity remained a significant predictor of the child's activity after
      adjustment for confounders. Children spent approximately 90 min.d in screen time
      (television, videos, DVD, and computers) with an additional 90 min in other
      sedentary activities (reading, drawing, and music). Physical activity was
      significantly reduced at 4 and 5 yr compared with 3 yr in both sexes, whether
      measured as AAC (24-h data, awake time only, weekend days, weekdays), time in
      moderate or vigorous activity, or from parental reports of activity. CONCLUSION:
      Levels of physical activity declined in boys and girls between the ages 3 and 4-5
      yr, whether using objective measures or parental reports of activity.

PMID- 19092703
TI  - Activity and barriers in girls (8-16 yr) based on grade and maturity status.
AB  - Minimal research has examined whether the decline in physical activity (PA) among
      adolescent girls is associated with chronological age (CA) or biological age
      (BA). PURPOSE: To describe the PA levels and perceived barriers to PA of
      adolescent girls grouped by school grade and maturity status (i.e., early or late
      maturing) within grades. METHODS: Two hundred and twenty-one girls (aged 8-16 yr,
      grades 4-10) wore an Actical accelerometer for 7 d and then completed a
      semistructured, open-ended questionnaire on perceived barriers to PA over the 7-d
      period. Predicted age at peak height velocity and recalled age at menarche were
      used to assess maturity among the elementary and high school girls, respectively.
      Maturity and grade group differences in PA were assessed using a MANCOVA and
      independent sample t-test and barriers to PA using chi-squared statistics.
      RESULTS: Daily minutes spent in moderate to vigorous PA decreased by 40% between
      grades 4 and 10. Within grade groupings, no differences in PA were found between
      early and late maturing girls (P > 0.05). Grades 4 to 6 participants cited more
      interpersonal (i.e., social) barriers. Grades 9 to 10 participants cited more
      institutional barriers to PA, primarily revolving around the institution of
      school. No differences were found in types of barriers reported between early and
      late maturing girls. CONCLUSION: Because PA and types of perceived barriers to PA
      were dependent on grade, future research should work to identify the most salient
      (i.e., frequent and limiting) barriers to PA by CA in youth. Once reliably was
      identified, multipronged intervention strategies must be tested for effectiveness
      to help youth cope with their salient barriers.

PMID- 19092704
TI  - Meeting the 60-min physical activity guideline: effect of operationalization.
AB  - PURPOSE: To investigate the effect of guideline operationalization in terms of
      intensity threshold, bout duration, and days on the proportion of children
      meeting the health-related 60-min physical activity guideline using a subjective
      and an objective assessment method. METHODS: Five hundred and twenty-one children
      (6-11 yr) completed a physical activity diary for at least 4 d. A subsample of 51
      children simultaneously wore an ActiGraph (ActiGraph, Pensacola, FL)
      accelerometer. Time spent above moderate-intensity thresholds of 3 and 5 METs,
      respectively, for continuous bouts of at least 1, 5, and 10 min was calculated.
      For each intensity threshold and bout duration, the proportion of children
      meeting the 60-min guideline was calculated. A distinction was made between
      meeting the 60-min threshold on each assessment day and meeting this threshold on
      average across all assessment days. RESULTS: The proportion of children meeting
      the 60-min guideline differed considerably by guideline operationalization and
      assessment method. It ranged from 3% to 86% using the diary and from 0% to 100%
      using the ActiGraph. Overall, a higher proportion of children met the guideline
      when the 3-MET intensity threshold was used compared with the 5-MET threshold and
      when a shorter bout duration was used compared with a longer bout duration. More
      children met the guideline on average across all assessment days compared with
      the guideline on each assessment day. In general, boys were found to be more
      active than girls, independent of guideline operationalization and assessment
      method. CONCLUSION: Meeting the 60-min guideline highly depends on guideline
      operationalization and assessment method. Consensus about how the guideline
      should be operationalized is needed to monitor the extent to which populations of
      children meet the guideline and to simplify comparison between studies.

PMID- 19092705
TI  - Incident hypercholesterolemia in relation to changes in vigorous physical
      activity.
AB  - PURPOSE: Test whether changes in vigorous exercise affect the risk for
      hypercholesterolemia. METHODS: : Incident physician-diagnosed
      hypercholesterolemia was compared in recreational runners whose weekly distances
      run increased >0.5 km x d (4034 men, 1897 women), remained constant (+/-0.5 km x
      d; 4685 men, 1904 women), or decreased >0.5 km x d (15,678 men, 6224 women)
      during 7.8 yr of prospective follow-up. RESULTS: Relative to those whose distance
      was maintained or reduced, the odds ratio (95% confidence interval) for
      hypercholesterolemia for those whose running increased was significantly less
      than 1 for men {0.82 (0.72-0.93), P = 0.0006}, women {0.71 (0.54-0.92), P =
      0.01}, and men and women combined adjusted for sex {0.80 (0.72-0.89), P <
      0.0001}. The significance of the odds ratios was somewhat diminished when
      adjusted for baseline and follow-up BMI in men {0.89 (0.79-1.01), P = 0.06},
      women {0.71 (0.54-0.92), P = 0.08}, and the adjusted sexes combined {0.88 (0.79
      0.98), P = 0.02}. When average distance run {i.e., (baseline + follow-up) / 2}
      was compared with incident hypercholesterolemia in the 6589 runners whose
      distance remained constant, each kilometer-per-day increment in average running
      distance was associated with an odds ratio significantly less than 1 in men {0.90
      (0.86-0.93)}, women {0.91 (0.84-0.98)}, and the adjusted sexes combined {0.90
      (0.87-0.93)}, which was also attributable in part to BMI in men {0.94 (0.90
      0.97), P = 0.0005}, women {0.96 (0.89-1.04), P = 0.35}, and the adjusted sexes
      combined {0.94 (0.91-0.97), P = 0.0003}. CONCLUSIONS: The odds for
      hypercholesterolemia 1) decrease in runners who increase their running mileage
      and 2) decline in association with the higher dose of vigorous activity even in
      the absence of any change in exercise. These effects are associated in part to
      the runners' BMI.

PMID- 19092706
TI  - Cardiovascular consequences of completing a 160-km ultramarathon.
AB  - PURPOSES: To comprehensively investigate the cardiovascular consequences of a 160
      km ultramarathon using traditional echocardiography, speckle tracking imaging,
      cardiac biomarkers, and heart rate variability (HRV) and to examine the
      relationship between the changes in these variables. METHODS: We examined
      athletes before an ultramarathon and reassessed all finishers immediately after
      the race. Left ventricular (LV) systolic (ejection fraction [EF], systolic blood
      pressure/end-systolic volume [SBP/ESV] ratio) and diastolic (ratio of early [E]
      to late [A], filling E:A) measurements were assessed using traditional
      echocardiography, whereas myocardial peak strain and strain rate were analyzed
      using speckle tracking. Cardiac biomarkers measured were cardiac troponin T
      (cTnT) and N-terminal pro-brain natriuretic peptide (NT-pro-BNP). HRV indices
      were assessed using standard frequency and time domain measures. RESULTS: Twenty
      five athletes successfully completed the race (25.5 +/- 3.2 h). Significant pre-
      to postrace changes in EF (66.8 +/- 3.8 to 61.2 +/- 4.0 %, P < 0.05) and E:A
      ratio (1.62 +/- 0.37 to 1.35 +/- 0.33, P < 0.05) were reported. Peak strain was
      significantly decreased in all planes, with the largest reduction occurring
      circumferentially. NT-pro-BNP concentrations increased significantly (28 +/- 17.1
      vs 795 +/- 823 ng x L, P < 0.05), whereas postrace cTnT were elevated in just
      five athletes (20%). No significant alterations in HRV were noted postrace.
      Reductions in LV function were not significantly associated with changes in
      cardiac biomarkers and/or HRV. CONCLUSIONS: Although the stress of an
      ultramarathon resulted in a mild reduction in LV function and biomarker release,
      the mechanisms behind such consequences remain unknown. It is likely that factors
      other than myocardial damage or strong vagal reactivation contributed to
      postexercise decreases in LV function after an ultramarathon.

PMID- 19092707
TI  - End-tidal CO2 pressure and cardiac performance during exercise in heart failure.
AB  - INTRODUCTION: In patients with heart failure (HF), end-tidal CO2 pressure
      (PetCO2) is related to ventricular function at rest and has been shown to predict
      prognosis. However, little is known about the association between ventricular
      performance and PetCO2 responses to exercise. METHODS: Forty-eight patients with
      HF and 13 normal subjects underwent cardiopulmonary exercise testing (CPX), while
      cardiac output and other hemodynamic measurements at rest and during exercise
      were obtained using a novel, noninvasive, bioreactance device based on assessment
      of relative phase shifts of electric currents injected across the thorax, heart
      rate, and ventricular ejection time. CPX responses and indices of cardiac
      performance were compared between normal subjects and HF patients achieving above
      and below a PetCO2 of 36 mm Hg at the ventilatory threshold (PetCO2@VT). RESULTS:
      HF patients with an abnormal PetCO2@VT (<36 mm Hg) had a lower exercise capacity,
      a lower .VO2@VT, a higher .V_E/.VCO2 slope, and lower oxygen uptake efficiency
      slope (OUES) values compared with normal subjects and patients achieving a normal
      PetCO2@VT. Patients with reduced PetCO2@VT had lower peak cardiac output
      responses to exercise (20.0 +/- 10, 17.8 +/- 6, and 13.7 +/- 7 L x min for normal
      subjects and HF patients with normal and abnormal PetCO2 responses to exercise,
      respectively, P = 0.04). PetCO2@VT was inversely related to the .V_E/.VCO2 slope
      (r = -0.78, P < 0.001) and directly related to the OUES (r = 0.55, P < 0.001).
      CONCLUSION: Reduced PetCO2 reflects impairments in the functional, ventilatory,
      and cardiac performance response to exercise in patients with HF. PetCO2 can
      supplement other clinical and CPX indices in the functional and prognostic
      evaluation of patients with HF.

PMID- 19092708
TI  - Central retinal vein occlusion in a sickle cell trait carrier after a cycling
      race.
AB  - A 26-yr-old man with sickle cell trait (SCT) suddenly lost visual acuity in the
      left eye after a cycling race in hot tropical environment. The cause was massive
      central retinal vein occlusion (CRVO) with hemorrhaging that rapidly worsened to
      neovascular glaucoma. Although medically treated, the eye is now marked by total
      retinal detachment. Cardiovascular function assessment shows no
      electrocardiographic abnormalities, no anomaly in the supra-aortic tree, and no
      evidence of structural heart disease. Although normal coagulation markers values
      (i.e., activated partial thromboplastin time, prothrombin time, fibrinogen
      concentration, antithrombin III, factor V, proteins C and S) were observed 2.5
      months after the clinical event, a transesophageal echocardiogram performed few
      hours after the incident revealed the presence of four thrombi in the left atrium
      suggesting a postexercise hypercoagulable state at that time. Hemorheological
      measurements at distance of the events demonstrated high red blood cell rigidity
      at baseline. Therefore, marked blood rheological impairment and activation of the
      coagulation pathway in response to the heavy and prolonged cycling race could
      have promoted CRVO in this cyclist carrying SCT. These data suggest that SCT
      could be considered as a risk factor for significant ocular complications when
      severe exercise is performed and support the idea that SCT is a contributing
      factor in blood rheology and vascular dysfunctions.

PMID- 19092709
TI  - Progressive statistics for studies in sports medicine and exercise science.
AB  - Statistical guidelines and expert statements are now available to assist in the
      analysis and reporting of studies in some biomedical disciplines. We present here
      a more progressive resource for sample-based studies, meta-analyses, and case
      studies in sports medicine and exercise science. We offer forthright advice on
      the following controversial or novel issues: using precision of estimation for
      inferences about population effects in preference to null-hypothesis testing,
      which is inadequate for assessing clinical or practical importance; justifying
      sample size via acceptable precision or confidence for clinical decisions rather
      than via adequate power for statistical significance; showing SD rather than SEM,
      to better communicate the magnitude of differences in means and nonuniformity of
      error; avoiding purely nonparametric analyses, which cannot provide inferences
      about magnitude and are unnecessary; using regression statistics in validity
      studies, in preference to the impractical and biased limits of agreement; making
      greater use of qualitative methods to enrich sample-based quantitative projects;
      and seeking ethics approval for public access to the depersonalized raw data of a
      study, to address the need for more scrutiny of research and better meta
      analyses. Advice on less contentious issues includes the following: using
      covariates in linear models to adjust for confounders, to account for individual
      differences, and to identify potential mechanisms of an effect; using log
      transformation to deal with nonuniformity of effects and error; identifying and
      deleting outliers; presenting descriptive, effect, and inferential statistics in
      appropriate formats; and contending with bias arising from problems with
      sampling, assignment, blinding, measurement error, and researchers' prejudices.
      This article should advance the field by stimulating debate, promoting innovative
      approaches, and serving as a useful checklist for authors, reviewers, and
      editors.

PMID- 19092710
TI  - Our 41st volume.

PMID- 19092712
TI  - Subjective visual vertical in acute attacks of Meniere's disease.
AB  - OBJECTIVES: To investigate whether or not and how often there is otolith
      dysfunction in an acute attack of Meniere's disease. PATIENTS: Twenty-two
      definite cases of unilateral Meniere's disease diagnosed in accordance with the
      1995 criteria of the American Academy of Otolaryngology-Head and Neck Surgery for
      Meniere's disease. INTERVENTION: Subjective visual vertical (SVV) test was
      performed before, at, and after acute attacks on 22 patients with unilateral
      Meniere's disease who showed normal tilts of SVV before acute attacks. MAIN
      OUTCOME MEASURE: Abnormal tilts of SVV. RESULTS: Of 22 cases, 14 (63.6%) with
      unilateral Meniere's disease showed abnormal tilts of SVV in acute attacks. The
      tilts were toward the side of the affected ear in 13 (92.9%) of them. Abnormal
      tilts returned to normal within a few weeks after the acute attacks in 12 (85.7%)
      of the 14 cases with unilateral Meniere's disease. CONCLUSION: Otolith
      dysfunction occurred in acute attacks in a considerable number of patients with
      Meniere's disease. Subjective visual vertical can be used as a good tool for the
      evaluation of otolith dysfunction at acute attacks in patients with Meniere's
      disease.

PMID- 19092711
TI  - Raloxifene use in clinical practice: efficacy and safety.
AB  - OBJECTIVE AND METHODS: In this article, we provide an interdisciplinary concise
      review of the effects of raloxifene on breast, bone, and reproductive organs, as
      well as the adverse events that may be associated with its use. RESULTS:
      Raloxifene has been shown to prevent osteoporosis in postmenopausal women (PMW)
      with low bone mass and prevent vertebral fractures in those with osteoporosis/low
      bone mass; it has not been shown to reduce the risk of nonvertebral fractures.
      Raloxifene reduces the risk of invasive breast cancer in PMW with osteoporosis or
      at high risk of breast cancer. The risk of venous thromboembolism has been
      consistently shown to be increased with raloxifene, so it should not be used in
      women at high risk of venous thromboembolism. Although raloxifene does not
      increase, nor decrease, the risk of coronary or stroke events overall, in the
      raloxifene trial of PMW at increased risk of coronary events, the incidence of
      fatal stroke was higher in women assigned raloxifene versus placebo. CONCLUSIONS:
      Based on its approved indications, it is appropriate to prescribe raloxifene to
      prevent or treat osteoporosis, as well as to reduce the risk of invasive breast
      cancer in PMW with osteoporosis or at high risk of breast cancer. Women at
      increased risk of both fracture and invasive breast cancer are those most likely
      to receive a dual benefit with raloxifene. Decision making must involve the
      incorporation of the woman's personal feelings about the risks and benefits of
      raloxifene therapy, balanced with her interest in reducing risk of fractures and
      breast cancer through pharmacological intervention.

PMID- 19092713
TI  - Transtympanic electrode positioning: manubrium is a poor guide.
AB  - BACKGROUND: Although a transtympanic electrode is commonly used for
      electrocochleography and electrically evoked auditory brainstem response, the
      variability of responses among healthy subjects is wide. The manubrium is the
      typical guidepost for electrode placement. This study addresses the hypothesis
      that electrode position relative to the round window niche is widely variable.
      STUDY DESIGN: : Postmortem anatomic dissection of 41 bequeathed adult crania (82
      temporal bones). METHODS: Drill marks were made on the medial wall of the
      mesotympanum from 2 manubrium-based positions: 1.5 to 2 mm posterior to the umbo,
      and halfway between the umbo and the annulus posteroinferior. RESULTS: Distances
      to the lip of the round window niche ranged from 0.8 to 3.5 mm and from 1.8 to
      4.5 mm for the 2 electrode sites, respectively. The posteriorly determined site
      was uniform on the promontory, but the posteroinferior site was into hypotympanic
      trabeculations in 81% of ears and into the jugular plate in 6%. Distances from
      the electrode sites to round window niche were not obviously associated with
      either the orientation of the manubrium in the head or the mastoid size.
      CONCLUSION: The location of a transtympanic positioned electrode using the
      manubrium as guidepost is not accurately predictable relative to the round window
      niche.

PMID- 19092714
TI  - Risk factors for hearing loss in US adults: data from the National Health and
      Nutrition Examination Survey, 1999 to 2002.
AB  - OBJECTIVE: To evaluate and compare the effects of cardiovascular risk factors
      (hypertension, smoking, diabetes) and noise exposure (occupational, recreational,
      firearm) on frequency-specific audiometric thresholds among US adults while
      assessing synergistic interactions between these exposures. DESIGN: National
      cross-sectional survey. SETTING/PARTICIPANTS: United States adults aged 20 to 69
      years who participated in the 1999 to 2002 National Health and Nutrition
      Examination Survey (N = 3,527). MAIN OUTCOME MEASURES: Air-conduction thresholds
      at 0.5 to 8 kHz (dB) in the poorer-hearing ear. Multivariate models adjusted for
      age, sex, race/ethnicity, and educational level. RESULTS: : Exposure to firearm
      noise was significantly associated with high-frequency (4-8 kHz) hearing loss
      (HL), whereas smoking and diabetes were associated with significantly increased
      hearing thresholds across the frequency range (0.5-8 kHz). A significant
      interaction was observed between exposure to firearm noise and heavy smoking such
      that firearm noise was associated with a mean 8-dB hearing loss in heavy smokers
      compared with a mean 2-dB hearing loss in nonsmokers at 8 kHz. We also observed
      significant interactions between firearm noise exposure and diabetes. CONCLUSION:
      Noise exposure was associated with high-frequency HL, whereas cardiovascular risk
      generated by smoking and diabetes was associated with both high- and low
      frequency HL. The frequency-specific effects of these exposures may offer insight
      into mechanisms of cochlear damage. We demonstrated an interaction between
      cardiovascular risk and noise exposures, possibly as a result of cochlear
      vulnerability due to microvascular insufficiency. Such significant interactions
      provide proof of principle that certain preexisting medical conditions can
      potentiate the effect of noise exposure on hearing. Data-based stratification of
      risk should guide our counseling of patients regarding HL.

PMID- 19092715
TI  - Expansile bone cyst and cholesteatoma of the temporal bone.
AB  - OBJECTIVE: To identify primary bony cysts of the temporal bone. PATIENT: A single
      case of a woman presenting with unilateral bulging of the temporoparietal
      cranium, progressive stenosis of the external auditory canal, and maximal
      conductive hearing loss. INTERVENTION(S): Plain x-rays, magnetic resonance
      imaging, contrast-enhanced computed tomography, audiogram, and modified radical
      mastoidectomy. MAIN OUTCOME MEASURE(S): Radiologic and histopathologic diagnosis
      of a primary bone cyst of the temporal bone obstructing the external auditory
      canal with a retained cholesteatoma of the middle ear. RESULTS: Identification of
      an inflammatory bony cyst of the temporal bone with a retained cholesteatoma of
      the middle ear resulting in stenosis of the external auditory canal and maximal
      conductive hearing loss. CONCLUSION: Primary bone cyst of the temporal bone can
      lead to external auditory canal stenosis, middle ear cholesteatoma, and
      conductive hearing loss.

PMID- 19092716
TI  - Early career development in academic pediatrics of participants in the APS-SPR
      Medical Student Research Program.
AB  - To recruit and train the next generations of pediatric clinician-scientists, the
      American Pediatric Society and Society for Pediatric Research initiated a program
      in 1991 to support medical students with interests in research and pediatrics to
      conduct research at institutions other than their respective medical schools.
      Since 1991, the American Pediatric Society-Society for Pediatric Research Medical
      Student Research Program (MSRP) has funded 732 of 2209 applicants from 132 US or
      Canadian medical schools for 8-12 wk of research under the direction of
      experienced investigators. PubMed-attributable publications tabulated in 2001 for
      MSRP applicants through 2000 indicated that participants had published more
      actively than had nonparticipant applicants. Male nonparticipants exhibited
      greater publication activities than did female nonparticipants, but female and
      male participants published equally. Of all MSRP participants between 1991 and
      1996, as of 2008, 36% were in pediatrics, and a remarkable 29% were in academic
      pediatrics.

PMID- 19092717
TI  - Differential effects of growth hormone and alpha calcidol on trabecular and
      cortical bones in hypophysectomized rats.
AB  - Growth hormone (GH) deficiency in children causes severe growth retardation,
      vitamin D deficiency, and osteopenia. We investigated whether alfacalcidol (1OHD)
      alone or in combination with GH can improve bone formation. Forty
      hypophysectomized female rats (HX) at the age of 8 wk were divided into HX, HX +
      1OHD (oral 0.25 microg/kg daily), HX+GH (0.666 mg/0.2 mL SC daily) and HX+GH +
      1OHD groups for a 4-wk study. Results showed that GH increased body weight, bone
      area, bone mineral content (BMC), and bone mineral density (BMD), whereas 1OHD
      only increased BMC and BMD. In cortical bone, GH increased both periosteal and
      endocortical bone formation resulting in a significant increase in cortical size
      and area in percentage, whereas 1OHD suppressed endocortical erosion surface per
      bone surface (ES/BS) without a significant effect on bone formation rate per bone
      surface (BFR/BS). In trabecular bone, GH mitigated the bone loss by increasing
      BFR/BS, whereas the 1OHD effect was by suppression of trabecular bone turnover in
      the HX rats. The combination of GH and 1OHD had no additive effect on increasing
      trabecular bone mass. In conclusion, GH activates new bone formation and
      increases bone turnover whereas 1OHD suppresses bone turnover. The combination
      intervention does not seem to provide any additive benefit.

PMID- 19092718
TI  - The effects of postnatal retinoic acid administration on nephron endowment in the
      preterm baboon kidney.
AB  - Administration of retinoic acid (RA), the active metabolite of vitamin A, is
      linked to the stimulation of nephrogenesis. The aim of this study was to
      determine whether early postnatal administration of RA could enhance ongoing
      nephrogenesis in a baboon model of premature birth. Unbiased stereological
      methods were used to estimate kidney volume, renal corpuscle volume, and nephron
      number. The percentage of abnormal glomeruli and the number of glomerular
      generations was also determined in the kidneys of preterm control (n = 6) and
      preterm +RA (n = 6) animals that received 500 microg/kg/d of all-trans RA after
      premature delivery. There was no significant difference between the preterm
      control and the preterm +RA groups in kidney size, nephron number (preterm
      control: 329,924 +/- 41,752; preterm +RA: 354,041 +/- 52,095; p = 0.59), renal
      corpuscle volume, number of glomerular generations, or the percentage of abnormal
      glomeruli. The proportion of abnormal glomeruli did not appear to be linked to
      any elements of postnatal care examined. The results of this study indicate that
      early postnatal administration of RA is unable to stimulate nephrogenesis in the
      kidney of the preterm baboon. Encouragingly, it does not appear to have any
      adverse effects on kidney development.

PMID- 19092719
TI  - Periconceptional undernutrition of ewes impairs glucose tolerance in their adult
      offspring.
AB  - Maternal undernutrition throughout pregnancy can have long-term effects on the
      health of adult offspring. Undernutrition around the time of conception alters
      growth, metabolism, and endocrinology of the sheep fetus, but the impact on
      offspring after birth is largely unknown. We determined the effect of maternal
      periconceptional undernutrition in sheep on glucose tolerance in the offspring
      before and after puberty. Undernourished (UN) ewes were fed individually to
      maintain weight loss of 10-15% bodyweight from 61 d before until 30 d after
      mating. Offspring (24 UN, 30 control) underwent an i.v. glucose tolerance test at
      4 and 10 mo of age. Glucose tolerance was similar in both groups at 4 mo. Insulin
      area under the curve increased by 33% between 4 and 10 mo (101 +/- 8 versus 154
      +/- 12 ng x min x mL(-1), p < 0.0001). At 10 mo, UN offspring had a 10% greater
      glucose area under the curve than controls (809 +/- 22 versus 712 +/- 20 mM x
      min, p < 0.01), a reduced first phase insulin response (p = 0.003) which was
      particularly apparent in females and in singletons, and a decreased
      insulin:glucose ratio (p = 0.01). We conclude that maternal undernutrition around
      the time of conception results in impaired glucose tolerance in postpubertal
      offspring.

PMID- 19092720
TI  - New potential adjuncts to treatment of children with type 1 diabetes mellitus.
AB  - Insulin administration is the primary therapy for type 1 diabetes mellitus
      (T1DM). Current available insulin therapies do not successfully enable children
      with T1DM to reach glycemic goals without side effects such as hypoglycemia and
      weight gain. Pramlintide is a synthetic analog of human amylin that acts in
      conjunction with insulin to delay gastric emptying and inhibit the release of
      glucagon and is indicated for use in patients with type 1 and type 2 diabetes.
      Recent studies in adult patients have examined the role of glucagon-like peptide
      1 (GLP-1) and agents that bind to its receptor in type 1 diabetes. It is
      hypothesized that a major component of the glycemic effect is attributable to the
      known action of GLP-1 to delay gastric emptying and to inhibit glucagon
      secretion. Further studies with the use of amylin analogs and long-acting GLP-1
      agonists as congeners with insulin in T1DM are indicated in children. In recent
      years, our better understanding of the pathophysiology of diabetes has led to the
      development of new therapies for diabetes. This article reviews the potential use
      of these newer pharmacologic agents as adjunctive therapy in T1DM in children and
      adolescents.

PMID- 19092721
TI  - Oxygen-induced tension in the sheep ductus arteriosus: effects of gestation on
      potassium and calcium channel regulation.
AB  - Compared with the full-term ductus arteriosus, the premature ductus is less
      likely to constrict when exposed to postnatal oxygen concentrations. We used
      isolated fetal sheep ductus arteriosus (pretreated with inhibitors of
      prostaglandin and nitric oxide production) to determine whether changes in K+ -
      and CaL-channel activity could account for the developmental differences in
      oxygen-induced tension. In the mature ductus, KV-channels appear to be the only
      K+-channels that oppose ductus tension. Oxygen concentrations between (2% and
      15%) inhibit KV-channel activity, which increases the CaL-channel-mediated
      increase in tension. Low oxygen concentrations have a direct inhibitory effect on
      CaL-channel activity in the immature ductus; this is not the case in the mature
      ductus. In the immature ductus, three different K+-channel activities (KV, KCa,
      and KATP) oppose ductus tension and contribute to its decreased tone. Oxygen
      inhibits the activities of all three K+ -channels. The inhibitory effects of the
      three K+-channel activities decline with advancing gestation. The decline in K+ 
      channel activity is not due to decreased K+ -channel expression. Super
      physiologic oxygen concentrations (>or=30% O2) constrict the ductus by using
      calcium-dependent pathways that are independent of K+- and CaL-channel
      activities. Super-physiologic oxygen concentrations eliminate the difference in
      tensions between the two age groups.

PMID- 19092722
TI  - Oxygen-induced retinopathy in mice: amplification by neonatal IGF-I deficit and
      attenuation by IGF-I administration.
AB  - In preterms, low serum levels of IGF (IGF-I) correlate with retinopathy of
      prematurity (ROP). In mice, IGF-I is a prerequisite for normal retinal
      development. We further explored the link between IGF-I and oxygen-induced
      retinopathy (OIR). To assess the role of endogenous IGF-I, pups were
      redistributed into smaller versus larger litters at birth; in one subgroup, we
      measured body weight and circulating IGF-I; in another, we applied hyperoxia and
      assessed retinal neovascularization (NV). To screen for the potential role of
      exogenous IGF-I, we administered a single bolus of rhIGF-I on postnatal day (P) 4
      to pups in normal litters, and applied hyperoxia; body weight and IGF-I were
      measured; maturation and NV were assessed. Neonatal mice in larger litters had a
      lower body weight than mice in smaller litters; they had lower levels of
      circulating IGF-I, and developed more OIR (p = 0.002). Mice who had received
      rhIGF-I, weighed more and had higher endogenous IGF-I levels; they matured faster
      and developed less OIR (p = 0.00001). These findings in mice are the first to
      support the notion that higher availability of endogenous or exogenous IGF-I
      reduces OIR risk, and thus sharpen the perspective that ROP may be preventable by
      briefly up-regulating IGF-I after birth.

PMID- 19092723
TI  - Lyonization effects of the t(X;16) translocation on the phenotypic expression in
      a rare female with Menkes disease.
AB  - Menkes disease (MD) is a rare and severe X-linked recessive disorder of copper
      metabolism. The MD gene, ATP7A (ATPase Cu++ transporting alpha polypeptide),
      encodes an ATP-dependent copper-binding membrane protein. In this report, we
      describe a girl with typical clinical features of MD, carrying a balanced
      translocation between the chromosomes X and 16 producing the disruption of one
      copy of ATP7A gene and the silencing of the other copy because of the chromosome
      X inactivation. Fluorescence in situ hybridization experiments with bacterial
      derived artificial chromosome probes revealed that the breakpoints were located
      within Xq13.3 and 16p11.2. Replication pattern analysis demonstrated that the
      normal X chromosome was late replicating and consequently inactivated, whereas
      the der(X)t(X;16), bearing the disrupted ATP7A gene, was active. An innovative
      approach, based on FMR1 (fragile X mental retardation 1) gene polymorphism, has
      been used to disclose the paternal origin of the rearrangement providing a new
      diagnostic tool for determining the parental origin of defects involving the X
      chromosome and clarifying the mechanism leading to the cytogenetic rearrangement
      that occurred in our patient.

PMID- 19092724
TI  - Longitudinal changes in high molecular weight serum adiponectin levels in healthy
      infants.
AB  - To determine the factors associated with high molecular weight adiponectin (HMW
      ad) levels during the first year of life, the longitudinal changes in serum HMW
      ad were investigated from birth to 12 mo of age. The total adiponectin levels,
      HMW-ad, and leptin were measured longitudinally from birth to 12 mo of age in 56
      healthy infants (>or=35 wk of gestation). Serum HMW-ad levels were positively
      correlated with total adiponectin levels (R2 = 0.93, p < 0.0001). Serum HMW-ad
      levels at birth, six, and 12 mo were 13.7 +/- 0.9 (mean +/- SE), 13.3 +/- 0.8,
      and 7.7 +/- 0.5 microg/mL, respectively. The levels at 12 mo were significantly
      lower than those at birth and 6 mo, respectively. In a multiple regression
      analysis, the HMW-ad levels at 12 mo were found to be related only to cord blood
      HMW-ad levels (beta = 0.680, p < 0.001) and not to any other factors. These
      results imply that postnatal production of HMW-ad at least during infancy may be
      regulated before birth. Further study is necessary to determine whether cord
      blood HMW-ad has an effect and whether it is involved in the development of
      metabolic syndrome.

PMID- 19092725
TI  - Pulmonary neuroendocrine cell-secreted factors may alter fetal lung liquid
      clearance.
AB  - The neuroendocrine system is most active at birth and may play a role in the
      transition from fetal to postnatal life, in particular in the lungs' transition
      from fluid secretion to fluid absorption. Pulmonary neuroendocrine cells do
      release dopamine (DA), serotonin, and gastrin-releasing peptide but their effects
      on lung ion and fluid transport are poorly understood. Therefore, we studied
      their effects on fetal distal lung explants and primary cultures of fetal distal
      lung epithelium (FDLE). We show that DA, but neither serotonin nor gastrin
      releasing peptide, alters ion and fluid transport, in a dose-dependent manner.
      DAs effects were abrogated by D1/D2 receptor blockers in FDLE but not in
      explants. Propranolol abrogated DAs effects in both models. DA increased
      intracellular cAMP levels in FDLE. Terbutaline, forskolin, and
      isobutylmethylxanthine did not increase short circuit current (Isc) in DA-treated
      cells, despite a further increase in cAMP. We conclude that at least one, but not
      all mediators released by pulmonary neuroendocrine cells alter distal lung
      epithelial ion transport.

PMID- 19092726
TI  - The emergence of human consciousness: from fetal to neonatal life.
AB  - A simple definition of consciousness is sensory awareness of the body, the self,
      and the world. The fetus may be aware of the body, for example by perceiving
      pain. It reacts to touch, smell, and sound, and shows facial expressions
      responding to external stimuli. However, these reactions are probably
      preprogrammed and have a subcortical nonconscious origin. Furthermore, the fetus
      is almost continuously asleep and unconscious partially due to endogenous
      sedation. Conversely, the newborn infant can be awake, exhibit sensory awareness,
      and process memorized mental representations. It is also able to differentiate
      between self and nonself touch, express emotions, and show signs of shared
      feelings. Yet, it is unreflective, present oriented, and makes little reference
      to concept of him/herself. Newborn infants display features characteristic of
      what may be referred to as basic consciousness and they still have to undergo
      considerable maturation to reach the level of adult consciousness. The preterm
      infant, ex utero, may open its eyes and establish minimal eye contact with its
      mother. It also shows avoidance reactions to harmful stimuli. However, the
      thalamocortical connections are not yet fully established, which is why it can
      only reach a minimal level of consciousness.

PMID- 19092727
TI  - Ontogeny of MMPs and TIMPs in the murine neocortex.
AB  - Matrix metalloproteinases (MMPs) and their tissue inhibitors (TIMPs) have been
      implicated in normal brain development, adult stroke, and, more recently,
      perinatal brain injury. Here, our objective was to obtain comprehensive and
      comparative data on the ontogeny of MMP-2, MMP-9, TIMP-1, and TIMP-2 in the
      neocortex of male and female mice belonging to various strains, from embryonic
      life to adulthood. We used gelatin zymography, ELISA, and real-time PCR analyses.
      MMP-2, MMP-9, and TIMP-1 activity and/or expression peaked during embryonic life
      and the early neonatal period, whereas TIMP-2 peaked during the first two
      postnatal weeks. Comparable results were obtained in all the mouse strains except
      BALB/c, where MMP-2 levels were considerably lower at all ages compared with the
      other strains. No gender effect was observed on any of the study parameters. This
      comprehensive study will serve as a basis for future investigations into the role
      for MMPs and TIMPs in normal brain development and prenatal brain injury.

PMID- 19092728
TI  - Causes of macular serous retinal detachments in Japanese patients 40 years and
      older.
AB  - PURPOSE: To investigate the causes of macular serous retinal detachment without
      hemorrhage at the macula in patients 40 years and older. METHODS: Seventy-one
      eyes of 71 consecutive Japanese patients 40 years and older with the disease were
      examined using optical coherence tomography, digital simultaneous fluorescein and
      indocyanine green angiographies with a confocal laser scanning system. RESULTS:
      Of 71 eyes, 17 eyes (24%) had central serous chorioretinopathy, including three
      eyes with chronic central serous chorioretinopathy, 40 eyes (56%) had polypoidal
      choroidal vasculopathy (PCV), 10 eyes (14%) had occult choroidal
      neovascularization secondary to age-related macular degeneration, one had Harada
      disease, and another had retinal macroaneurysms. In two eyes, the diagnosis could
      not be established because of difficulty differentiating among chronic central
      serous chorioretinopathy, PCV, and occult choroidal neovascularization. Thirty
      eight of 59 (64%) eyes of patients in the sixth decade of life and older had PCV.
      CONCLUSIONS: Polypoidal choroidal vasculopathy is a primary cause of macular
      serous retinal detachment without hemorrhage in Japanese patients over 50 years
      of age. Since clinical and fluorescein angiographic findings are
      indistinguishable among central serous chorioretinopathy, PCV, and occult
      choroidal neovascularization, indocyanine green angiography might help to
      establish a more definitive diagnosis.

PMID- 19092729
TI  - A randomized comparison of parecoxib/valdecoxib and placebo for the prevention of
      cystoid macular edema after scleral buckling surgery.
AB  - AIMS: To assess the impact of valdecoxib on the incidence of macular edema, after
      scleral buckling surgery. METHODS: Prospective randomized double masked placebo
      controlled study. Patients undergoing scleral buckle surgery over 18 months were
      recruited and randomized to receive either oral valdecoxib or placebo. Patients
      also received two doses of either parecoxib (pro-drug of valdecoxib)
      intravenously 40 mg 6 hourly day one postoperative or identical placebo injection
      Patients underwent retinal examination, optical coherence tomography and retinal
      thickness analyzer scan of the macula preoperatively, and at 2 and 6 weeks
      postoperatively. Outcome measures were the incidence of macular edema, retinal
      thickness, visual acuity, contrast sensitivity and presence of persistent
      subretinal fluid. RESULTS: Interim analysis was performed with 116 patients were
      recruited, 58 to each treatment arm. The incidence of macular edema in all
      patients was 5% at visit 1 and 2.2% at visit 2 postoperatively. This incidence
      was much lower than the expected incidence used in the power calculation to
      determine study size. It was therefore apparent that a much larger study
      population would be required to test for an effect and that this was not
      achievable within the study time period. The study was therefore terminated
      early. There was no evidence of a difference between COX 2 inhibitor and placebo
      groups in the incidence of edema, retinal thickness or visual outcome. The
      presence of residual subretinal fluid at the macula was significantly reduced by
      COX 2 inhibitor treatment. CONCLUSIONS: The rate of cystoid macular edema after
      scleral buckling surgery is low and is not influenced by prophylactic use of
      valdecoxib. The rate of residual subretinal fluid was reduced by COX 2 inhibitor
      treatment. Enhanced antiinflammatory therapy has the potential to improve
      outcomes in scleral buckling surgery.

PMID- 19092730
TI  - Classification of full-thickness traumatic macular holes by optical coherence
      tomography.
AB  - PURPOSE: To describe morphologic features of traumatic macular holes on optical
      coherence tomography and to correlate them with clinical findings. METHODS:
      Seventy-three consecutive patients diagnosed with full-thickness traumatic
      macular holes involving the fovea underwent complete ophthalmic evaluation
      followed by horizontal and vertical line scans using the Stratus optical
      coherence tomography. Retinal thickness at the edges of the holes, apical and
      basal diameters, and various clinical parameters were recorded. The approximate
      apical and basal areas and eccentricities of the holes were calculated.
      Morphologic parameters were correlated with clinical findings. RESULTS: On the
      basis of optical coherence tomography findings, traumatic macular holes were
      classified into five morphologic types with varying average retinal thicknesses,
      apical areas, and basal areas. Patients who presented >90 days after injury had
      greater average retinal thickness (P = 0.03) and apex areas (P = 0.002) compared
      with those who presented within 90 days. Older patients developed more circular
      holes, i.e., less eccentricity of the apex (P = 0.04) and base (P = 0.01).
      Interestingly, none of the morphologic parameters investigated in the current
      study correlated with visual acuity. Patients who presented later in the clinical
      course or who had greater average retinal thicknesses tended to have better
      vision (P = 0.11 and P = 0.07, respectively). CONCLUSIONS: Optical coherence
      tomography evaluation may yield important insights into the pathogenesis and
      clinical findings of traumatic macular holes.

PMID- 19092731
TI  - A head-tilt test for hypopyon after intravitreal triamcinolone.

PMID- 19092732
TI  - Retinal functional changes measured by microperimetry in neovascular age-related
      macular degeneration patients treated with ranibizumab.
AB  - PURPOSE: To assess functional and structural retinal changes in patients with
      neovascular age-related macular degeneration treated with intravitreal
      ranibizumab 0.5 mg. METHODS: Eighteen patients with neovascular age-related
      macular degeneration have been evaluated in this retrospective 24-week follow-up
      study. All patients were treated with three injections of ranibizumab 0.5 mg, 1
      month apart and retreated according to predefined criteria. At baseline, all
      patients were subjected to visual acuity measurement, fluorescein angiography,
      microperimetry, and optical coherence tomography stratus. Visual acuity,
      microperimetry, and optical coherence tomography evaluations were repeated 28 +/-
      2 days after each injection. RESULTS: Mean retinal sensitivity significantly
      improved from 3.89 +/- 3.0 dB at baseline to 6.61 +/- 3.4 dB at 24 weeks (P =
      0.044). Mean visual acuity significantly improved from 48.67 +/- 8.58 to 60.72 +/
      16.09 (P = 0.026); visual acuity improved in 44.4% of patients > or =15 letters
      (24.5 +/- 8.0 letters), and in 38.9% of patients improved <15 letters (6.14 +/-
      3.7 letters); 16.7% of patients lost <15 letters (7.3 +/- 2.1 letters). An
      improvement of fixation stability from baseline was observed in 33.3% of
      patients. Central macular thickness significantly decreased from 310.5 +/- 85.7
      microm to 217.3 +/- 46.8 microm at 24 weeks (P < 0.001). CONCLUSIONS: Although
      visual acuity and retinal thickness changes seemed to be almost maximum at 4
      weeks after intravitreal ranibizumab 0.5 mg, retinal sensitivity as measured by
      microperimetry showed a trend of progressive improvement till 24 weeks suggesting
      that microperimetry may give additional information about macular function not
      given by visual acuity alone.

PMID- 19092733
TI  - Plasma NT-proBNP levels and the risk of atrial fibrillation after major lung
      resection.
AB  - AIM: Supraventricular tachyarrhythmias, most frequently atrial fibrillation (AF),
      occur in 8-30% of patients undergoing major pulmonary resection. The aim of this
      study was to characterize a biochemical marker in order to identify subjects at
      higher risk of postoperative AF. The authors tested the hypothesis that elevated
      preoperative plasma levels of N-terminal brain-type natriuretic peptide (NT-pro
      BNP) may predict the occurrence of postoperative AF. METHODS: Fifty-five
      consecutive patients undergoing elective major thoracic surgery were selected.
      All patients had 12-lead electrocardiogram and transthoracic echocardiographic
      evaluation at entry. Plasma NT-pro BNP levels were determined both at baseline
      and at the first postoperative day. Patients were monitored thereafter to detect
      the occurrence of AF. For statistical analysis, an unpaired Student t test was
      used to compare continuous variables, chi(2) tests or Fischer exact tests were
      used for categorical variables, as needed. RESULTS: Eight (14.54%) of the 55
      patients developed AF with a peak incidence on postoperative days 2 to 3.
      Baseline NT-pro-BNP was more than two fold higher in patients who developed AF
      (506.1+/-108.4 pg/mL versus 197.7+/-54.9 pg/mL; P=0.001). Other relevant clinical
      and diagnostic parameters were not different in the two groups. Patients with NT
      pro-BNP level above the median (113.0 pg/mL) had 8-fold increase risk of
      postoperative AF. CONCLUSION: A preoperative elevated plasma NT-pro-BNP level was
      associated with the occurrence of AF in patient undergoing major thoracic
      surgery. Baseline NT-pro-BNP levels may be proposed as a biochemical marker to
      detect patients at higher risk of postoperative AF who could benefit from
      prophylactic therapeutic medication.

PMID- 19092735
TI  - Peripheral obstructive arterial disease and carotid artery stenosis in end stage
      renal disease: a case-control study.
AB  - AIM: Cardiovascular diseases are an important cause of morbidity and mortality in
      end stage renal disease (ESRD) patients. The purpose of this study was to
      evaluate the predominance of carotid stenosis and peripheral obstructive arterial
      disease (POAD) in a group of patients subject to dialysis compared with a control
      group. METHODS: It is a control-case study performed on patients at different
      hemodialysis facilities; the exams were carried out in ambulatory care. Two
      groups of patients were examined, the first group was made up of 40 dialysis
      patients (46.6% men, average age 58.8), the second was the control group made up
      of 58 subjects matched by age, sex, arterial pressure, presence of diabetes and
      smoking habits. All patients underwent an Eco-Color Doppler exam on the over
      aortal trunks and lower extremities and had their Ankle-Brakial-Index (ABI)
      measured. Carotid stenosis was considered only if equal or over 50%. RESULTS:
      Twenty percent of dialysis patients showed carotid stenosis (CS) versus 12% in
      the control group, with an OR of 7.9 (CI 95% 1.3-47.7) adjusted to sex, age and
      hypertension. The ultrasound picture of the lesions showed large amounts of
      calcium deposits. Predominance of POAD in dialysis patients was 20% versus 9% in
      the control group. In dialysis patients the OR adjusted to age, sex and arterial
      pressure was 6.3 (CI 95%, 1.2-32.6). CONCLUSION: The ultrasound picture of the
      lesions showed mainly underpopliteal lesions with ''rosary bead'' calcifications.
      In diabetic dialysis patients the OR was 7.6 (CI 95% 1.4-46.3).

PMID- 19092734
TI  - Global cardiac evaluation without heart rate control: preliminary experience with
      dual source CT (DSCT).
AB  - AIM: The aim of this work was to assess the role of dual source computed
      tomography (DSCT) in global cardiac evaluation without heart rate control,
      assessing the effect of average heart rate on coronary image quality, optimal
      reconstruction interval, ventricular function, and evaluation of left chamber
      valves. METHODS: Fifteen consecutive patients under-went coronary CT angiography.
      For coronary evaluation, data sets were reconstructed in 5% steps from 30% to 80%
      of the RR interval. For the assessment of cardiac function, image were
      reconstructed with a slice thickness of 2.0 mm and 2.0 mm increment, at 10% steps
      from 0% to 90% of the RR interval. Two blinded independent readers assessed the
      image quality of the coronary arteries and left chamber valves. RESULTS: The mean
      heart rate during the scan was 73+/-11.8 bpm (range 56-97). At the best
      reconstruction interval excellent diagnostic image quality (score 4) was achieved
      in 95.5% (43/45) of coronary arteries. Excellent inter-observer agreement was
      observed for image quality rating (k=0.82). No significant correlation was found
      between the average heart rate and the mean quality scores (rho=0.29). Comparison
      of image quality of the coronary arteries in systolic and diastolic
      reconstructions in each patient showed no statistically significant differences.
      CONCLUSION: DSCT is an excellent technique for global cardiac imaging, as it
      allows to obtain coronary arteries of excellent quality and evaluate ventricular
      function and valvular area independent of the heart rate.

PMID- 19092736
TI  - Treatment strategies in atrial fibrillation.
AB  - Atrial fibrillation (AF) is the most common cardiac arrhythmia in clinical
      practice affecting up to 1% of the general population. There is a higher
      prevalence and incidence with increasing age and burden of chronic heart disease
      . Treatment for AF represents a significant healthcare cost, estimated to be
      about Euro 13.5 billion annually in the European Union. Manage-ment of AF remains
      challenging especially with new pharmacological and non-pharmacological
      approaches becoming readily available. This review article discusses the
      multitude of therapeutic options and how they may be applied to best effect.

PMID- 19092737
TI  - Catheter-based cryoablation of atrial fibrillation: state of the art.
AB  - Catheter-based ablation has been adopted as second-line therapy for both
      paroxysmal and persistent atrial fibrillation (AF) and is currently investigated
      as a primary approach. Reported success rates of catheter-based radiofrequency
      (RF) ablation vary between 65% and 85% depending on the technique used, patient
      selection and experience of the center. However, catheter ablation of AF is not
      without risk. In a worldwide survey major complications were reported in up to 6%
      of the procedures. Also, in high volume centers a complication rate of 5% is
      reported, which declined after excluding the learning curve during the first 100
      procedures to 4.3%. These complications and the observation that AF-ablation
      using RF-energy is a demanding procedure in terms of operator competency and
      dexterity limiting the world-wide availability of this therapy lead to an
      extensive search for alternative energy and delivery sources. In four studies
      from Europe the new cryoballoon approach is effective and safe and appears to
      have a similar success rate than RF-ablation at least in paroxysmal AF and
      normally sized left atria. Changes in catheter design and additional equipment
      will probably improve this technique. Further clinical studies should focus on a
      head-to-head comparison between cryoablation and RF-ablation in AF. The favou
      rable risk profile of cryoenergy might pave the way for cryoballoon ablation as a
      first-line treatment option in patients with paroxysmal AF.

PMID- 19092738
TI  - Outcome of atrial fibrillation ablation: assessment of success.
AB  - Atrial fibrillation (AF) is the most common sustained cardiac arrhythmia with a
      prevalence in the general population of approximately 1%. Catheter ablation has
      emerged from being a highly experimental procedure to one of the most common
      ablation performed in many electrophysiology laboratories throughout the world.
      The stability of sinus rhythm restored by catheter ablation is important not only
      for comparison of different ablation techniques, but also for guiding
      anticoagulation and possible antiarrhythmic drug treatment. It has been shown
      that asymptomatic AF after ablation is at least as common as before the ablation.
      Rhythm assessment is therefore a key component of post AF ablation follow-up. A
      variety of electrocardiogram (ECG) monitoring techniques is available. Besides of
      technical characteristics such as the number of recording leads and further
      signal processing, these techniques differ mainly in the duration of ECG
      recordings and the involvement of the patient. Intermittent rhythm monitoring
      techniques include standard 12-lead ECG, Holter-ECG of various duration, patient
      activated external loop ECG recorder as well as patient activated transtelephonic
      ECG monitor. Continuous ECG represents the gold standard for rhythm monitoring
      recording and can be achieved by means of a pacemaker, implan-table defibrillator
      or implantable cardiac ECG monitor.

PMID- 19092739
TI  - Prevention of thromboembolic complications in patients with atrial fibrillation.
AB  - Atrial fibrillation (AF) is a major arrhythmia in clinical practice, and its
      frequency rises rapidly from the sixth decade onward. Its most serious clinical
      consequence is ischemic stroke. Patients with AF have a five-fold increased risk
      of stroke compared to those in sinus rhythm. Advancing age, prior stroke or
      transient cerebral ischemia, diabetes, hypertension, and impaired function of the
      left ventricle are known risk factors. On the basis of data from several
      randomized controlled clinical trials and pooled analyses, several guidelines
      have been published to promote the use of anticoagulant treatment to prevent
      stroke in patients with AF. The management of oral anticoagulant therapy needs
      regular monitoring of INR, which should be kept in the narrow therapeutic range
      of 2.0-3.0 most of the time, with adjustments of the dose as required. Only a
      small proportion of patients with AF whom best-practice guidelines identify as
      eligible for oral anticoagulant therapy actually receive it. Inconvenience of
      monitoring and frequent dose adjustments, together with fear of major hemorrhage
      associated with oral anticoagulants, contribute to this underuse. In particular,
      conventional intensity of anticoagulation increases the risk of intracranial
      hemorrhage, and patients with advanced age are more prone to cerebral bleeding
      than younger patients. Up to date, the efficacy of aspirin, an antiplatelet
      agent, for stroke prevention in AF patients is less clear and remains
      controversial and alternative pharmacological treatment options have failed to
      demonstrate their superiority over vitamin K antagonists.

PMID- 19092740
TI  - Ablation of atrial fibrillation in congestive heart failure.
AB  - Atrial fibrillation frequently coexists with heart failure, and these two chronic
      disease states often physiologically exacerbate one another. Clinical trials
      comparing rate versus rhythm control strategies have not demonstrated superiority
      with one strategy over the other, with pharmacologically based rhythm management.
      Since 1998, catheter-based ablation strategies for the treatment of atrial
      fibrillation have grown rapidly. Although prospective randomized trial data is
      lacking, observational cohort studies have demonstrated efficacy in patients with
      heart failure as well as recovery of myocardial systolic function and functional
      status in a significant proportion of patients undergoing ablation of atrial
      fibrillation.

PMID- 19092742
TI  - Left atrial appendage exclusion system for stroke prevention in atrial
      fibrillation: a percutaneous device delivery approach.
AB  - Atrial fibrillation (AF) is a well-known predisposing factor for stroke. Most of
      the thrombi responsible for these ischemic events originate in the left atrial
      appendage. Left atrium appendage (LAA) occlusion is a potential alternative to
      warfarin in patients with atrial fibrillation who have contraindications to
      anticoagulation. The Percutaneous LAA Transcatheter Occlusion (PLAATO System, ev3
      Inc., Plymouth, Minnesota) and the WATCHMAN LAA system (Atritech Inc., Plymouth,
      Minnesota), are currently the two devices specifically designed for LAA
      occlusion. Although available data are still limited, LAA occlusion is
      technically feasible, with good intermediate results, but its long-term safety
      and ability to reduce stroke incidence remains unproven. Randomized studies will
      clarify the usefulness of the LAA occlusion devices as an alternative treatment
      strategy to long-term anticoagulation.

PMID- 19092741
TI  - The intriguing problem of atrial fibrillation in competitive athletes.
AB  - Atrial fibrillation (AF) is the most frequent cause of prolonged palpitations in
      young competitive athletes, even including those performing elite sport activity.
      This arrhythmia may occasionally affect impair athletes' ability to compete thus
      leading to non-eligibility at prequalification screening. Competitive sport has a
      significant impact on the autonomous nervous system. In fact, long-term regular
      intense physical training determines an increase in vagal tone leading to resting
      bradycardia. During physical activity, particularly in the setting of
      competition, a marked release of catecholamines occurs as a result of both the
      intense physical effort and emotional stress. Both of these adaptive phenomena
      may precipitate AF. Furthermore, in several athletes with AF an association with
      sick sinus syndrome has been found, even though the pathophysiological basis of
      this finding is not clear. This picture is further complicated by the
      increasingly intake of illicit substances, whose arrhythmogenic effect has been
      shown both at the ventricular and atrial levels. Moreover, the use of
      recreational drugs, such as amphetamines, ecstasy, alcohol, cannabinoids, cocaine
      and so called new drugs in clubs has dramatically increased, with several cases
      of drug-induced arrhythmic events. These effects are often exacerbated by the
      combined use of different drugs, especially in situations such as sports
      competitions, in which the adrenergic system is already hyperactivated. No data
      have been published on the efficacy of antiarrhythmic therapy in athletes with
      AF, but it has been reported that athletes are more predisposed to the
      development of pro-arrhythmic effects induced by antiarrhythmic drugs when
      compared to general population. Most recently, radiofrequency catheter ablation
      involving electrical disconnection of the pulmonary veins in athletes with AF
      limiting their normal training activity and participation in sports competitions
      has proven highly effective to restore stable sinus rhythm and enable subsequent
      re-eligibility.

PMID- 19092743
TI  - Hypertrophic cardiomyopathy: individualized therapy for a heterogeneous disease.
AB  - It is now 50 years since the modern description of hypertrophic cardiomyopathy
      (HCM). The initial descriptions foretold the current efforts towards sudden death
      prevention, alleviation of heart failure symptoms and angina, relief of left
      ventricular outflow tract obstruction, preparticipation athletic screening,
      family screening and genetic testing. The authors review the salient features of
      HCM, focusing on therapeutic strategies to manage its symptoms and attempts to
      prevent sudden death.

PMID- 19092744
TI  - Safety of coronary collateral stenting in a patient with acute coronary syndrome.
AB  - A protective role of the presence of collateral arteries, generating smaller
      infarcts, improved ventricular function, fewer future cardiovascular events, and
      improved survival following a myocardial ischemia has been described in numerous
      reports. However little is known about atherosclerotic disease of the collateral
      vessels, and the possibility to treat critical stenosis of these vessels has
      never been described. Therefore this report describes a unique case of
      percutaneous coronary intervention on a well developed yet atherosclerotic
      coronary collateral vessel triggering an acute coronary syndrome with hemodynamic
      instability. In the present case balloon angioplasty and stenting of the
      collateral vessel was safe and effective. Nonetheless, further studies are
      warranted.

PMID- 19092745
TI  - Heparin induced thrombocytopenia in patients with ventricular assistance device
      bridge-to-transplantation. A case series.
AB  - Heparin-induced thrombocytopenia (HIT), is a severe side effect of heparin. It
      occurs both in patients treated with unfractionated heparin (UFH) and in patients
      treated with low molecular weight heparin (LMWH). It is associated with anti
      heparin/platelet factor (PF4) antibodies. HIT is a rare pathology, with rates
      going from 8% to 10% in patients in ventricular assist device support. The
      authors present three clinical cases which occurred in the Department of
      Anesthesiology of the Civil Hospital of Strasbourg (France) in patients receiving
      biventricular assistance bridge-to- cardiac transplantation. All the three
      patients were hospitalized for myocardial infarction. In case 1 HIT was diagnosed
      on VI day postoperative after a ventricular assistance device (VAD) implant. The
      patient was treated with lepirudin and transplanted after 73 days. In case 2 HIT
      diagnosis was made after 9 days receiving VAD. Also this patient was treated with
      lepirudin and transplanted after 48 days. Both case 1 and 2 received intra-aortic
      balloon pump (IABP) assistance before receiving VAD. Case 3 received VAD on XXII
      day of hospitalization; the patient developed HIT after 5 days, which was treated
      with lepirudin. He was transplanted after 66 days, but he died in course of
      intervention. HIT in patients undergoing VAD bridge-to-transplantation is a rare
      and often misdiagnosed cause of thrombocytopenia. Correct diagnosis, management
      and therapy are mandatory in this kind of patients, but they are not easy and
      standardized.

PMID- 19092746
TI  - Intracardiac echocardiography-aided diagnosis of superior caval sinus defect in
      case of contraindications to non-invasive imaging tools.

PMID- 19092747
TI  - Hybrid revascularization for acute myocardial infarction complicated by
      cardiogenic shock: left main coronary artery recanalization as a bridging
      procedure.

PMID- 19092748
TI  - An uncommon case of syncope in a 4-year-old child affected by a long QT syndrome.

PMID- 19092749
TI  - Aneurysm of the superior thyroid artery in a 80-year-old man: case report.

PMID- 19092750
TI  - Malignant melanoma metastatic to the right atrium: clinical findings of an
      asyntomatic case.

PMID- 19092752
TI  - DNA Checkerboard method for bacterial detection of microbiota from teeth and
      tongue biofilms. A preliminary study.
AB  - AIM: The aim of this study was to determine the prevalence of 13 bacterial
      species in the dorsum tongue biofilm and compare its microbiota to that of
      subgingival samples in healthy adult subjects using DNA Checkerboard
      hybridization. METHODS: A total of 40 samples, from subgingival and tongue
      biofilm, were enrolled into the study. All the samples were harvested and
      analyzed by DNA Checkerboard method for their content of 13 species of bacteria.
      Bacterial scores from each subject and location were averaged and the results of
      both sites were compared using the Wilcoxon signed ranks test. RESULTS: All the
      microorganisms evaluated were detected in both tongue and subgingival samples,
      without significant differences in their prevalence. CONCLUSIONS: The dorsum of
      the tongue was colonized by various microorganisms with similar prevalence as
      found in the subgingival biofilm of healthy individuals, suggesting that the
      tongue could be a potential microbial reservoir and may play a role in the
      recolonization of teeth surfaces.

PMID- 19092753
TI  - Evaluation of root resorption associated with orthodontic movement in stressed
      rats.
AB  - AIM: The aim of this study was to investigate the effects of acute and chronic
      systemic stress response on orthodontically induced root resorption. METHODS:
      Male Wistar rats were restrained during 1 hour a day by stress models of short (3
      days) and long duration (40 days), while control group was not submitted to
      restraint (N.=10/group). The upper left first molars of all rats were moved
      mesially by a fixed orthodontic appliance exerting 50 g force upon insertion
      during the last 14 days of the experiment. Then, animals were killed for blood
      collection and mensuration of plasmatic corticosterone by radioimmunoassay; the
      tissues around mesial root of the first molar were processed for histological and
      histochemical techniques with tartrate-resistant acid phosphatase. The degree of
      root resorption and the number of odontoclasts were evaluated, being the
      contralateral side of each animal serving as its control (split-mouth design).
      RESULTS: The results revealed that the plasmatic levels of corticosterone were
      significantly higher in both the stressed groups than in the control one. There
      were no significant differences in the degree of root resorption and in the
      number of odontoclasts on the root between the 3 groups studied. CONCLUSIONS:
      These results indicate that systemic stress alone can not be considered a risk
      factor for root resorption induced by orthodontic tooth movement.

PMID- 19092754
TI  - Changes in hardness and surface topography of tissue conditioners submitted to
      chemical disinfection.
AB  - AIM: The aim of this study was to evaluate the longitudinal effect of chemical
      disinfection on Shore A hardness, surface roughness (Ra) and morphology of two
      tissue conditioners (Dura Conditioner [DC] and Softone [SO]). METHODS: Twenty
      four specimens (2 mm-thick) were made of each material and randomly divided into
      three groups (N.=8): control (no disinfection), 10 000 ppm chloride solution
      (sodium hypochlorite) and Corega Tabs solution (peroxide solution). Soaking was
      performed daily for 15 min, and Shore A hardness and Ra were measured at baseline
      and 3, 7, 10, and 14 days. Data were analyzed by repeated measures ANOVA and
      Bonferroni's test (alfa= 0.05). RESULTS: Chemical disinfection for 14 days with
      sodium hypochlorite and Corega Tabs affected differently the tested materials.
      Hardness varied from 8 to 20 for DC and from 8 to 23 for SO with significant
      interaction (P<0.05) between material and disinfection treatment up to day 7. Ra
      values (in microm) varied from 1.51 to 4.35 for DC and from 2.08 to 4.15 for SO;
      there was a significant difference between disinfection treatments (P=0.043) but
      not between materials (P=0.119). Sodium hypochlorite groups displayed smaller Ra
      values than the control groups, but did not differ from Corega Tabs groups.
      Scanning electron microscopy showed different pattern of degradation for each
      material. CONCLUSIONS: The results suggest that the effect of chemical
      disinfection on degradation of tissue conditioners is material-specific, but
      hardness is less affected than surface topography. The overall results support
      the use of the tested materials for up to three days, independently from the
      disinfection treatment.

PMID- 19092755
TI  - Endoscopic management of a lateral root lesion. A case report.
AB  - The aim of this study was to obtain periradicular tissue healing of a lateral
      root lesion using a microsurgical technique. The case report concerns a 52-year
      old female patient, in general good health (ASA1), presented with the left
      maxillary canine (2.3) exhibiting acute, specific symptoms. A radiographic
      examination revealed the presence of a circumscribed radiolucent lesion
      associated with the mesial mid-root area of the 2.3 and the distal mid-root area
      of 2.2, both endodontically treated. Using an endoscope as a magnification device
      a surgical inspection of the middle-third of the root of 2.2 and 2.3 was made. A
      pathway between the periodontium and root-canal system was detected with an
      endodontic file on the middle-third of 2.3 root wall. A root-lateral cavity was
      prepared using retro-tips. An EBA cement was used as the root-end filling
      material. Following clinical and radiographic assessment at 36 months post
      surgery, the case was classified as successful. This case report showed the
      utility of using an endoscope and micro-surgical instruments for diagnosis and
      surgical treatment of micro-anatomical root structures.

PMID- 19092756
TI  - Reconstruction of an unusual orocutaneous fistula by using a bilobed flap.
AB  - Orocutaneous fistulas or cutaneous sinus tracts of dental origin are pathologic
      communications between the cutaneous surface of the face and the oral cavity.
      They are relatively uncommon and may be easily misdiagnosed. In this report,
      management of an orocutaneous fistula of dental origin, which endured for 20
      years, by using an extraoral bilobed skin flap, an intraoral buccal rotational
      mucosal flap and allogenic bone graft, is presented.

PMID- 19092757
TI  - Outbreak of histoplasmosis among travelers returning from El Salvador-
      Pennsylvania and Virginia, 2008.
AB  - Histoplasmosis is a fungal disease caused by infection with Histoplasma
      capsulatum. Histoplasmosis, which can be acquired from soil contaminated with
      bird or bat droppings, occurs worldwide and is one of the most common pulmonary
      and systemic mycoses in the United States. However, among international travelers
      returning from areas in which histoplasmosis is endemic, histoplasmosis is rare,
      accounting for <0.5% of all diseases diagnosed in this group. During February
      March 2008, the Pennsylvania and Virginia departments of health investigated a
      cluster of respiratory illness among three mission groups that had traveled
      separately to El Salvador to renovate a church. This report summarizes the
      results of the investigation. Of 33 travelers in the three mission groups for
      whom information was available, 20 (61%) met the case definition for
      histoplasmosis. Persons who reported sweeping and cleaning outdoors (relative
      risk [RR] = 2.1, 95% confidence interval [CI] = 1.3-3.6), digging (RR = 2.6, CI =
      1.1-6.1), or working in a bird or bat roosting area (RR = 1.8, CI = 1.3-2.4) had
      a greater risk for illness. The findings emphasize the need for travelers and
      persons involved in construction activities to use personal protective equipment
      and decrease dust-generation when working in areas where histoplasmosis is
      endemic. Clinicians should consider histoplasmosis as a possible cause of acute
      respiratory or influenza-like illness in travelers returning from areas in which
      histoplasmosis is endemic.

PMID- 19092758
TI  - Effects of new penicillin susceptibility breakpoints for Streptococcus pneumoniae
      -United States, 2006-2007.
AB  - Streptococcus pneumoniae (pneumococcus) is a common cause of pneumonia and
      meningitis in the United States. Antimicrobial resistance, which can result in
      pneumococcal infection treatment failure, is identified by measuring the minimum
      inhibitory concentration (MIC) of an antimicrobial that will inhibit pneumococcal
      growth. Breakpoints are MICs that define infections as susceptible (treatable),
      intermediate (possibly treatable with higher doses), and resistant (not
      treatable) to certain antimicrobials. In January 2008, after a reevaluation that
      included more recent clinical studies, the Clinical and Laboratory Standards
      Institute (CLSI) published new S. pneumoniae breakpoints for penicillin (the
      preferred antimicrobial for susceptible S. pneumoniae infections). To assess the
      potential effects of the new breakpoints on susceptibility categorization, CDC
      applied them to MICs of invasive pneumococcal disease (IPD) isolates collected by
      the Active Bacterial Core surveillance (ABCs) system at sites in 10 states during
      2006-2007. This report summarizes the results of that analysis, which found that
      the percentage of IPD nonmeningitis S. pneumoniae isolates categorized as
      susceptible, intermediate, and resistant to penicillin changed from 74.7%, 15.0%,
      and 10.3% under the former breakpoints to 93.2%, 5.6%, and 1.2%, respectively,
      under the new breakpoints. Microbiology laboratories should be aware of the new
      breakpoints to interpret pneumococcal susceptibility accurately, and clinicians
      should be aware of the breakpoints to prescribe antimicrobials appropriately for
      pneumococcal infections. State and local health departments also should be aware
      of the new breakpoints because they might result in a decrease in the number of
      reported cases of penicillin-resistant pneumococcus.

PMID- 19092759
TI  - Respiratory syncytial virus activity-- United States, July 2007-December 2008.
AB  - Respiratory syncytial virus (RSV) is the most common cause of bronchiolitis and
      pneumonia in children aged <1 year and is a major cause of respiratory illness in
      older adults. RSV is transmitted person-to-person via close contact, droplets,
      and fomites. Each year in the United States, an estimated 75,000-125,000 children
      aged <1 year are hospitalized with RSV. Those at increased risk for
      hospitalization include premature infants meeting certain criteria and persons of
      any age with compromised respiratory, cardiac, and immune systems. RSV incidence
      follows a seasonal pattern. In temperate climates, the RSV season generally
      occurs during the fall, winter, and spring months. However, the timing of RSV
      circulation can vary by location and year. CDC analyzed laboratory data from the
      National Respiratory and Enteric Virus Surveillance System (NREVSS) to summarize
      RSV temporal and geographic trends in the United States during the weeks ending
      July 7, 2007--June 28, 2008, and for the first 5 months of the current reporting
      season (the weeks ending July 5-December 6, 2008). This report describes the
      results of that analysis, which indicated that the 2007-08 RSV season onset for
      the 10 U.S. Department of Health and Human Services (HHS) regions and Florida
      ranged from early July to mid-December, and the season offset ranged from late
      January to mid-April; the current 2008-09 season onset occurred in eight of the
      10 HHS regions by December 6, 2008. These findings support previous observations
      that the RSV season not only varies by location, but can vary by year.

PMID- 19092760
TI  - Genetic variation and constraints on the evolution of defense against spittlebug
      (Philaenus spumarius) herbivory in Mimulus guttatus.
AB  - Plants mediate carbon into most ecosystems and are thus under persistent attack
      by diverse enemies. The evolution of defense against such assaults will depend on
      the availability of genetic variation, as well as the costs and constraints on
      defense. We estimated the magnitude of genetic variation for defense against
      spittlebug (Philaenus spumarius) herbivory in Mimulus guttatus using a diallel
      cross-grown in a greenhouse. Except for flowering time, additive genetic
      variation for the plant traits we measured was negligible, regardless of
      herbivory environment. In contrast, nonadditive genetic variation contributed
      significantly to all plant traits measured. We found significant additive genetic
      variation among plants for biomass of adult spittlebugs, suggesting heritability
      for resistance to herbivory. The other putative resistance trait measured,
      spittlebug maturation time, was not significantly heritable. We found no evidence
      for significant genetic variation for tolerance to herbivory except for a small
      non-nuclear paternal contribution to tolerance for flower number. Additive
      genetic correlations indicated that more resistant plant genotypes (in terms of
      adult spittlebug biomass) were also smaller in the absence of spittlebugs,
      suggesting a potential cost of resistance to herbivory. We found no other
      significant genetic correlations indicating a cost of defense, nor did we find
      evidence for a tradeoff between resistance and tolerance to herbivory. Overall,
      these results suggest the future adaptive evolution of tolerance to spittlebugs
      in this population will be limited primarily by available genetic variation,
      whereas the future evolution of antibiosis resistance may be constrained by
      allocation costs of resistance.

PMID- 19092766
TI  - Mesenchymal stem cells and neurodegenerative disease.
AB  - The prospect of cell therapy for incurable neurodegenerative disease excites
      scientists, the public, and patients alike. Clinical and scientific enthusiasm
      must, however, always be tempered by methodological rigor and by the overwhelming
      imperative of protecting vulnerable sufferers. We tentatively suggest that, in
      the case of autologous mesenchymal stem cells (MSCs), the balance between our
      current understanding of their biology and an informed assessment of their
      probable safety allows a case to be made for cautious pilot clinical studies.

PMID- 19092767
TI  - Safety issues of maternal drug therapy during breastfeeding.
AB  - Two goals when counseling breastfeeding mothers taking medication are protecting
      the infant from adverse events and permitting necessary maternal therapy. Madadi
      et al. report a case-control study of neonatal and maternal opioid toxicity after
      codeine administration. Therapeutic considerations in counseling breastfeeding
      mothers include susceptibility to drug toxicity of the very young and/or
      premature infant, significant interindividual variations in drug response, the
      dose-response relationship with respect to drug toxicity, and the role of
      pharmacogenetics in both the mother and the infant. These host factors may
      combine in a particular patient to act synergistically to produce an adverse
      reaction.

PMID- 19092770
TI  - A composite-likelihood approach for identifying polymorphisms that are
      potentially directly associated with disease.
AB  - If a linkage signal can be fully accounted for by the association of a particular
      polymorphism with the disease, this polymorphism may be the sole causal variant
      in the region. On the other hand, if the linkage signal exceeds that explained by
      the association, different or additional directly associated loci must exist in
      the region. Several methods have been proposed for testing the hypothesis that
      association with a particular candidate single-nucleotide polymorphism (SNP) can
      explain an observed linkage signal. When several candidate SNPs exist, all of the
      existing methods test the hypothesis for each candidate SNP separately, by
      fitting the appropriate model for each individual candidate SNP. Here we propose
      a method that combines analyses of two or more candidate SNPs using a composite
      likelihood approach. We use simulations to demonstrate that the proposed method
      can lead to substantial power increases over the earlier single SNP analyses.

PMID- 19092771
TI  - Dopamine receptor D3 gene and essential tremor in large series of German, Danish
      and French patients.
AB  - The genetic causes of essential tremor (ET) seem to be heterogeneous. Recently,
      ET has been found associated with a functional variant (Ser9Gly) of the dopamine
      D(3) receptor (DRD3), located in the ETM1 locus on chromosome 3q13.3 described
      for the first time in 1997. We examined this variant in three different
      populations from Germany, Denmark and France. We undertook an association study
      of the Ser9Gly variant in 202 cases with a familial history from unrelated
      families with ET, 97 cases with isolated non-familial ET and 528 healthy
      controls. In addition, linkage and segregation analyses were carried out in 22 ET
      families. The distribution of genotypes and allele frequencies showed no
      significant differences in the whole sample and in a subanalysis of familial and
      sporadic cases. Age at onset of tremor, tremor duration and tremor severity did
      not show an association with the genotype. In addition, the DRD3 variant was not
      found linked to the disease in a subset of informative ET families. We did not
      find a significant association of the DRD3 variant with ET nor linkage to the
      DRD3 receptor in German, Danish and French ET patients and families, suggesting
      that it is unlikely to be a causal factor for ET.

PMID- 19092772
TI  - Genomics and breast cancer: the different levels of inherited susceptibility.

PMID- 19092773
TI  - Breast cancer susceptibility: current knowledge and implications for genetic
      counselling.
AB  - Breast cancer is the most common malignancy in women in the Western world. Except
      for the high breast cancer risk in BRCA1 and BRCA2 mutation carriers as well as
      the risk for breast cancer in certain rare syndromes caused by mutations in TP53,
      STK11, PTEN, CDH1, NF1 or NBN, familial clustering of breast cancer remains
      largely unexplained. Despite significant efforts, BRCA3 could not be identified,
      but several reports have recently been published on genes involved in DNA repair
      and single nucleotide polymorphisms (SNPs) associated with an increased breast
      cancer risk. Although candidate gene approaches demonstrated moderately increased
      breast cancer risks for rare mutations in genes involved in DNA repair (ATM,
      CHEK2, BRIP1, PALB2 and RAD50), genome-wide association studies identified
      several SNPs as low-penetrance breast cancer susceptibility polymorphisms within
      genes as well as in chromosomal loci with no known genes (FGFR2, TOX3, LSP1,
      MAP3K1, TGFB1, 2q35 and 8q). Some of these low-penetrance breast cancer
      susceptibility polymorphisms also act as modifier genes in BRCA1/BRCA2 mutation
      carriers. This review not only outlines the recent key developments and potential
      clinical benefit for preventive management and therapy but also discusses the
      current limitations of genetic testing of variants associated with intermediate
      and low breast cancer risk.

PMID- 19092774
TI  - Gains in power for exhaustive analyses of haplotypes using variable-sized sliding
      window strategy: a comparison of association-mapping strategies.
AB  - Linkage disequilibrium (LD)-based association mapping is often performed by
      analyzing either individual SNPs or block-based multi-SNP haplotypes. Sliding
      windows of several fixed sizes (in terms of SNP numbers) were also applied to a
      few simulated or real data sets. In comparison, exhaustively testing based on
      variable-sized sliding windows (VSW) of all possible sizes of SNPs over a genomic
      region has the best chance to capture the optimum markers (single SNPs or
      haplotypes) that are most significantly associated with the traits under study.
      However, the cost is the increased number of multiple tests and computation.
      Here, a strategy of VSW of all possible sizes is proposed and its power is
      examined, in comparison with those using only haplotype blocks (BLK) or single
      SNP loci (SGL) tests. Critical values for statistical significance testing that
      account for multiple testing are simulated. We demonstrated that, over a wide
      range of parameters simulated, VSW increased power for the detection of disease
      variants by approximately 1-15% over the BLK and SGL approaches. The improved
      performance was more significant in regions with high recombination rates. In an
      empirical data set, VSW obtained the most significant signal and identified the
      LRP5 gene as strongly associated with osteoporosis. With the use of computational
      techniques such as parallel algorithms and clustering computing, it is feasible
      to apply VSW to large genomic regions or those regions preliminarily identified
      by traditional SGL/BLK methods.

PMID- 19092775
TI  - Significant evidence for linkage to chromosome 5q13 in a genome-wide scan for
      asthma in an extended pedigree resource.
AB  - Asthma is a multifactorial disease with undetermined genetic factors. We
      performed a genome-wide scan to identify predisposition loci for asthma. The
      asthma phenotype consisted of physician-confirmed presence or absence of asthma
      symptoms. We analyzed 81 extended Utah pedigrees ranging from three to six
      generations, including 742 affected individuals, ranging from 2 to 40 per
      pedigree. We performed parametric multipoint linkage analyses with dominant and
      recessive models. Our analysis revealed genome-wide significant evidence of
      linkage to region 5q13 (log of the odds ratio (LOD)=3.8, recessive model), and
      suggestive evidence for linkage to region 6p21 (LOD=2.1, dominant model). Both
      the 5q13 and 6p21 regions indicated in these analyses have been previously
      identified as regions of interest in other genome-wide scans for asthma-related
      phenotypes. The evidence of linkage at the 5q13 region represents the first
      significant evidence for linkage on a genome-wide basis for this locus. Linked
      pedigrees localize the region to approximately between 92.3-105.5 Mb.

PMID- 19092776
TI  - Impact of inbreeding on fertility in a pre-industrial population.
AB  - Little is known about the effects of inbreeding on reproduction in modern human
      societies. It appears indeed that biological effects are hidden by socioeconomic
      factors, which are the major determinants of fertility. It has been established,
      in particular, that socially induced reproductive compensation tends to
      homogenize the number of offspring per family in a given population. Besides, in
      the field of evolutionary biology, a number of empirical and theoretical studies
      have shown that the effects of inbreeding are condition dependent. In particular,
      theoretical developments on the evolution of senescence predict that the
      deleterious effects of inbreeding should increase with age. We rely on these
      developments to examine the effects of inbreeding on fertility in a cohort of
      Canadian women born in the late 19th century. The analysis does not allow for the
      detection of any effect of inbreeding on the overall number of offspring of
      women. However, results indicate that high levels of close father inbreeding are
      associated with a reduction of the productivity of parents during the second half
      of their reproductive period, as compared with the first half. We suggest that
      inbreeding depression affects reproduction in modern societies through an
      interaction with age.

PMID- 19092778
TI  - Variable number of tandem repeat polymorphisms of DRD4: re-evaluation of
      selection hypothesis and analysis of association with schizophrenia.
AB  - Associations have been reported between the variable number of tandem repeat
      (VNTR) polymorphisms in the exon 3 of dopamine D4 receptor gene gene and multiple
      psychiatric illnesses/traits. We examined the distribution of VNTR alleles of
      different length in a Japanese cohort and found that, as reported earlier, the
      size of allele '7R' was much rarer (0.5%) in Japanese than in Caucasian
      populations (approximately 20%). This presents a challenge to an earlier proposed
      hypothesis that positive selection favoring the allele 7R has contributed to its
      high frequency. To further address the issue of selection, we carried out
      sequencing of the VNTR region not only from human but also from chimpanzee
      samples, and made inference on the ancestral repeat motif and haplotype by use of
      a phylogenetic analysis program. The most common 4R variant was considered to be
      the ancestral haplotype as earlier proposed. However, in a gene tree of VNTR
      constructed on the basis of this inferred ancestral haplotype, the allele 7R had
      five descendent haplotypes in relatively long lineage, where genetic drift can
      have major influence. We also tested this length polymorphism for association
      with schizophrenia, studying two Japanese sample sets (one with 570 cases and 570
      controls, and the other with 124 pedigrees). No evidence of association between
      the allele 7R and schizophrenia was found in any of the two data sets.
      Collectively, this study suggests that the VNTR variation does not have an effect
      large enough to cause either selection or a detectable association with
      schizophrenia in a study of samples of moderate size.

PMID- 19092777
TI  - The PDGF-C regulatory region SNP rs28999109 decreases promoter transcriptional
      activity and is associated with CL/P.
AB  - Human linkage and association studies suggest a gene(s) for nonsyndromic cleft
      lip with or without cleft palate (CL/P) on chromosome 4q31-q32 at or near the
      platelet-derived growth factor-C (PDGF-C) locus. The mouse Pdgfc(-/-) knockout
      shows that PDGF-C is essential for palatogenesis. To evaluate the role of PDGF-C
      in human clefting, we performed sequence analysis and SNP genotyping using 1048
      multiplex CL/P families and 1000 case-control samples from multiple geographic
      origins. No coding region mutations were identified, but a novel -986 C>T SNP
      (rs28999109) was significantly associated with CL/P (P=0.01) in cases from
      Chinese families yielding evidence of linkage to 4q31-q32. Significant or near
      significant association was also seen for this and several other PDGF-C SNPs in
      families from the United States, Spain, India, Turkey, China, and Colombia,
      whereas no association was seen in families from the Philippines, and Guatemala,
      and case-controls from Brazil. The -986T allele abolished six overlapping
      potential transcription regulatory motifs. Transfection assays of PDGF-C promoter
      reporter constructs show that the -986T allele is associated with a significant
      decrease (up to 80%) of PDGF-C gene promoter activity. This functional
      polymorphism acting on a susceptible genetic background may represent a component
      of human CL/P etiology.

PMID- 19092779
TI  - Hypomethylation at multiple maternally methylated imprinted regions including
      PLAGL1 and GNAS loci in Beckwith-Wiedemann syndrome.
AB  - Genomic imprinting is an epigenetic phenomenon restricting gene expression in a
      manner dependent on parent of origin. Imprinted gene products are critical
      regulators of growth and development, and imprinting disorders are associated
      with both genetic and epigenetic mutations, including disruption of DNA
      methylation within the imprinting control regions (ICRs) of these genes. It was
      recently reported that some patients with imprinting disorders have a more
      generalised imprinting defect, with hypomethylation at a range of maternally
      methylated ICRs. We report a cohort of 149 patients with a clinical diagnosis of
      Beckwith-Wiedemann syndrome (BWS), including 81 with maternal hypomethylation of
      the KCNQ1OT1 ICR. Methylation analysis of 11 ICRs in these patients showed that
      hypomethylation affecting multiple imprinted loci was restricted to 17 patients
      with hypomethylation of the KCNQ1OT1 ICR, and involved only maternally methylated
      loci. Both partial and complete hypomethylation was demonstrated in these cases,
      suggesting a possible postzygotic origin of a mosaic imprinting error. Some ICRs,
      including the PLAGL1 and GNAS/NESPAS ICRs implicated in the aetiology of
      transient neonatal diabetes and pseudohypoparathyroidism type 1b, respectively,
      were more frequently affected than others. Although we did not find any evidence
      for mutation of the candidate gene DNMT3L, these results support the hypotheses
      that trans-acting factors affect the somatic maintenance of imprinting at
      multiple maternally methylated loci and that the clinical presentation of these
      complex cases may reflect the loci and tissues affected with the epigenetic
      abnormalities.

PMID- 19092780
TI  - Pharmacokinetic considerations for new targeted therapies.

PMID- 19092781
TI  - Accruing preclinical evidence about metabotropic glutamate 5 receptor antagonists
      as treatments for drug dependence highlights the irreplaceable contributions of
      animal studies to the discovery of new medications for human disorders.

PMID- 19092783
TI  - Neuroelectric signatures of reward learning and decision-making in the human
      nucleus accumbens.
AB  - Learning that certain actions lead to risky rewards is critical for biological,
      social, and economic survival, but the precise neural mechanisms of such reward
      guided learning remain unclear. Here, we show that the human nucleus accumbens
      plays a key role in learning about risks by representing reward value. We
      recorded electrophysiological activity directly from the nucleus accumbens of
      five patients undergoing deep brain stimulation for treatment of refractory major
      depression. Patients engaged in a simple reward-learning task in which they first
      learned stimulus-outcome associations (learning task), and then were able to
      choose from among the learned stimuli (choosing task). During the learning task,
      nucleus accumbens activity reflected potential and received reward values both
      during the cue stimulus and during the feedback. During the choosing task, there
      was no nucleus accumbens activity during the cue stimulus, but feedback-related
      activity was pronounced and similar to that during the learning task. This
      pattern of results is inconsistent with a prediction error response. Finally,
      analyses of cross-correlations between the accumbens and simultaneous recordings
      of medial frontal cortex suggest a dynamic interaction between these structures.
      The high spatial and temporal resolution of these recordings provides novel
      insights into the timing of activity in the human nucleus accumbens, its
      functions during reward-guided learning and decision-making, and its interactions
      with medial frontal cortex.

PMID- 19092782
TI  - Nicotine exposure during adolescence induces a depression-like state in
      adulthood.
AB  - There is a strong link between tobacco consumption and mood disorders. It has
      been suggested that afflicted individuals smoke to manage mood, however, there is
      evidence indicating that tobacco consumption can induce negative mood. This study
      was designed to investigate whether nicotine exposure during adolescence
      influences emotionality/behavioral functioning later in life. Adolescent
      (postnatal days, PD 30-44) male rats were treated with twice-daily injections of
      nicotine (0, 0.16, 0.32, or 0.64 mg/kg) for 15 consecutive days, and their
      behavioral reactivity to various behavioral paradigms (the elevated plus maze
      (EPM), sucrose preference, locomotor activity in the open field, and forced swim
      test (FST) was assessed 24 h (short term) or 1-month (long term) after exposure.
      Separate groups of adult rats received nicotine (0.32 mg/kg) to control for age
      dependent effects. We report that nicotine exposure during adolescence-but not
      adulthood-leads to a depression-like state manifested in decreased sensitivity to
      natural reward (sucrose), and enhanced sensitivity to stress- (FST) and anxiety
      eliciting situations (EPM) later in life. Our data show that behavioral
      dysregulation can emerge 1 week after drug cessation, and that a single day of
      nicotine exposure during adolescence can be sufficient to precipitate a
      depression-like state in adulthood. We further demonstrate that these deficits
      can be normalized by subsequent nicotine (0.32 mg/kg) or antidepressant (ie
      fluoxetine or bupropion; 10 mg/kg) treatment in adulthood. These data suggest
      that adolescent exposure to nicotine results in a negative emotional state
      rendering the organism significantly more vulnerable to the adverse effects of
      stress. Within this context, our findings, together with others indicating that
      nicotine exposure during adolescence enhances risk for addiction later in life,
      could serve as a potential model of comorbidity.

PMID- 19092784
TI  - Involvement of inferior parietal lobules in prospective memory impairment during
      acute MDMA (ecstasy) intoxication: an event-related fMRI study.
AB  - Prospective memory refers to the realization of delayed intentions. Several
      studies have shown that 3,4-methylenedioxy-methamphetamine (MDMA) users perform
      worse on measures of prospective memory as compared to nondrug users.
      Interpretation of these data may be limited because of polydrug use, psychosocial
      stressors, and increased psychopathology that have been reported in MDMA users.
      This study was designed to directly assess the pharmacological effect of MDMA on
      prospective memory and brain activity in a double-blind, placebo-controlled,
      cross-over study. Twelve recreational MDMA users received MDMA 75 mg and placebo
      and performed an objective prospective memory task during functional imaging.
      During prospective memory task performance subjects were engaged in a foreground
      task that consisted of a simple reaction time to visual stimuli (Go trials) and a
      prospective task of withholding a response during trials that were part of a
      dynamic memory set (No go trials). Behavioral data showed that a single dose of
      MDMA increased prospective memory failures in the No go trials, and that number
      of prospective memory failures was positively correlated to MDMA concentration in
      plasma. Functional imaging showed that MDMA decreased BOLD activation during Go
      trials in the thalamus (left), putamen (left), precuneus (left), and the inferior
      parietal lobules (bilateral), as compared to placebo. During No go trials, MDMA
      reduced BOLD deactivation in the inferior parietal lobules (bilateral), as
      compared to placebo. It is concluded that the loss of deactivation in inferior
      parietal lobules may account for increments in memory failures observed during
      MDMA intoxication.

PMID- 19092786
TI  - Can hyperthyroidism relapse after antithyroid drug treatment be predicted in
      children with Graves disease?

PMID- 19092787
TI  - Does comorbidity affect the benefit of intensive glycemic control in older
      patients with type 2 diabetes mellitus?

PMID- 19092785
TI  - Continuous glucose monitoring: long live the revolution!

PMID- 19092788
TI  - What is the optimal regimen for preventing hepatitis B recurrence after liver
      transplantation?
AB  - The outcome of liver transplantation for hepatitis B has markedly improved in the
      last two decades. This commentary discusses the findings and limitations of a
      study by Hwang et al., which retrospectively examined the outcome of 639 adult
      patients who underwent living donor liver transplantation for hepatitis B. The
      authors reported a 5-year HBV recurrence rate of 7.3% and concluded that high
      dose hepatitis B immunoglobulin (HBIG) monotherapy and rescue antiviral therapy
      is an effective way to prevent HBV recurrence after liver transplantation. With
      the availability of safe and effective antiviral agents associated with low rates
      of drug resistance, HBIG monotherapy is rarely used. The standard approach
      involves administration of antiviral therapy to suppress HBV replication before
      transplantation, followed by a combination of HBIG and antiviral therapy after
      transplantation. Combination prophylaxis permits the dose of HBIG to be reduced,
      which results in cost savings and reduces rates of HBV recurrence.

PMID- 19092789
TI  - Predictors of early rebleeding and mortality after acute variceal hemorrhage in
      patients with cirrhosis.
AB  - Despite improvements over the past 20 years in patient survival following
      episodes of acute variceal hemorrhage (AVH) secondary to cirrhosis, AVH is still
      associated with a high rate of mortality. The ability to predict which patients
      are at high risk of death, or which are not likely to respond to standard therapy
      at admission to hospital is important, as it enables the immediate initiation of
      vasoactive drugs, early endoscopic intervention and prophylactic antibiotics.
      This commentary discusses a study that attempts to predict early rebleeding and
      mortality after AVH in patients with cirrhosis using the Model for End-stage
      Liver Disease. In this study, the model was a significant predictor of mortality;
      however, several defects in the study's design limit the conclusions that can be
      drawn from it. The model described in this study is neither more useful, nor more
      accurate, than those previously published for the prediction of rebleeding and
      mortality in patients with AVH.

PMID- 19092790
TI  - What is the safe duration of therapy for patients infected with HCV genotype 6?
AB  - Very few studies have been published on response to treatment and treatment
      duration of patients infected with HCV genotype 6. This commentary discusses a
      study by Nguyen et al. that confirms that standard therapy is associated with a
      high-virologic response in patients infected with HCV genotype 6. This study also
      reported that patients who had chronic HCV infection with genotype 6 had a higher
      rate of sustained virologic response to 48 weeks of treatment with pegylated
      interferon plus ribavirin than to 24 weeks of treatment with the same combination
      of drugs. Although these results are promising, they need to be validated in a
      large prospective study before general conclusions can be drawn.

PMID- 19092791
TI  - Is the antidepressant venlafaxine effective for the treatment of functional
      dyspepsia?
AB  - Several studies have suggested that antidepressants might be beneficial in the
      treatment of patients with functional gastrointestinal disorders. This commentary
      discusses the results of a high-quality, multicenter, randomized, double-blind,
      placebo-controlled trial that showed no benefit of the antidepressant venlafaxine
      over placebo in the treatment of a large group of patients with functional
      dyspepsia. Moreover, venlafaxine was poorly tolerated by a considerable number of
      patients. The routine use of venlafaxine and other serotonin and norepinephrine
      reuptake-inhibitor antidepressants to treat patients with functional dyspepsia
      is, therefore, not recommended. Whether certain subgroups of patients,
      particularly those with anxious or depressive psychiatric comorbidities, might
      benefit from treatment with this class of antidepressants, however, remains to be
      elucidated. Antidepressants with different mechanisms of actions, for example
      mirtazapine, might still prove beneficial for the treatment of functional
      dyspepsia, but no clinical studies have yet investigated the efficacy of these
      drugs in this setting.

PMID- 19092792
TI  - Nurse-administered propofol sedation for upper endoscopic ultrasonography: not
      yet ready for prime time.
AB  - In nurse-administered propofol sedation (NAPS), a nurse working under the
      supervision of an endoscopist is delegated responsibility for administration of
      propofol to a patient and monitoring their sedation during endoscopy. Nursing
      personnel and endoscopists involved in NAPS receive specialized training, and
      more than 400,000 reported procedures (mostly esophagogastroduodenoscopies and
      colonoscopies) have used NAPS. The safety record of NAPS is comparable if not
      superior to that of standard sedation using an opioid and a benzodiazepine. A
      study by Fatima et al. attempts to expand the breadth of NAPS applications by
      testing the safety of the procedure in endoscopic ultrasonographies. This
      commentary discusses the results reported by Fatima et al., and urges clinicians
      to interpret this study's findings with caution. Further evidence that NAPS can
      be implemented for endoscopic ultrasonography in settings other than major
      hospitals with a full complement of services is necessary before its use can be
      recommended to community-based practices.

PMID- 19092793
TI  - Predicting thrombosis in systemic lupus erythematosus.
AB  - Biomarkers that reliably identify or even predict disease manifestations in
      systemic lupus erythematosus (SLE) are needed. In a recent issue of the Clinical
      Journal of the American Society of Nephrology, Wu and colleagues reported on the
      predictive value of routine D-dimer measurements for future thromboembolic events
      in patients enrolled in the Ohio SLE study, a unique prospective, longitudinal
      evaluation of individuals with recurrently active SLE. As in other disease
      settings, low D-dimer levels (<0.5 microg/ml) excluded clotting at a given time
      point and identified a zero risk of future clotting events. Conversely, 42% of
      patients with a high D-dimer level (>2.0 microg/ml) subsequently experienced a
      clinically relevant clotting event, in some cases in the absence of
      antiphospholipid antibodies or lupus anticoagulant. This Practice Point
      commentary considers whether the D-dimer assay will remain simply a tool to rule
      out thrombosis in symptomatic patients with SLE or whether it could eventually be
      used to initiate preventive anticoagulation in asymptomatic patients.

PMID- 19092794
TI  - Acute kidney injury caused by intravascular hemolysis after mechanical
      thrombectomy.
AB  - BACKGROUND: A 43-year-old African-American female (gravida 5 para 0) with an 8
      week intrauterine pregnancy presented to the emergency room with crampy abdominal
      pain, shortness of breath, and shoulder pain. She had normal renal function on
      admission. CT angiography of the chest revealed bilateral pulmonary emboli;
      therefore, the AngioJet (Possis Medical, Inc., Minneapolis, MN) device was used
      to perform mechanical thrombolysis. The patient subsequently developed
      hyperkalemia, red urine and anuria. INVESTIGATIONS: Physical examination,
      measurement of serum creatinine level and electrolytes, dipstick urinalysis and
      centrifugation of urine and blood. DIAGNOSIS: Acute kidney injury due to
      hemoglobinuria as a result of non-immune-mediated intravascular hemolysis
      following the use of a percutaneous mechanical thrombectomy device (AngioJet).
      MANAGEMENT: Hydration, alkalinization of urine and initiation of hemodialysis
      (temporarily switched to continuous venovenous hemodiafiltration). Urine output
      improved after the 20th day of hospitalization, at which point dialysis was
      discontinued. The patient's renal function completely recovered by day 25.

PMID- 19092795
TI  - Phenotypic heterogeneity and genetic modifiers in prion disease caused by a
      Pro102Leu mutation in the PRNP gene.
AB  - This Practice Point commentary describes the findings of a study by Webb et al.
      in which the researchers investigated phenotypic heterogeneity and disease
      modifying factors in a large series of patients with inherited prion disease
      caused by a mutation in the PRNP gene that results in a Pro102Leu amino acid
      substitution. This mutation is traditionally associated with Gerstmann-Straussler
      Scheinker syndrome (GSS), and the clinical presentation in most patients in the
      study fitted into the GSS spectrum, but a subset presented with prominent
      cognitive impairment. In addition, the authors noted remarkable interfamilial and
      intrafamilial variability with respect to age at disease onset (range 27-66
      years) and disease duration (range 7-132 months). Importantly, a polymorphism at
      PRNP codon 129 and the apolipoprotein E genotype were both identified as factors
      that modified the age at onset. These findings could have important implications
      for genetic counseling of individuals at risk from prion disease.

PMID- 19092796
TI  - Renal ischemia-reperfusion leads to long term infiltration of activated and
      effector-memory T lymphocytes.
AB  - It is well-established that significant ischemia-reperfusion injury during kidney
      transplantation results in increased incidence of long-term fibrosis and
      rejection. To test for a role of T cell infiltration and activation following
      ischemic injury, we induced both bilateral and unilateral renal ischemia in mice,
      followed by reperfusion, and then isolated mononuclear cells. Analysis of these
      cells by flow cytometry showed that 2 weeks after bilateral ischemia there was a
      significant increase of CD8(+) T cells. Furthermore, both CD4(+) and CD8(+) T
      cells infiltrated the injured kidney 6 weeks after unilateral ischemia. These T
      cells had increased expression of CD69(+) and CD44(hi)CD62L(-), markers of
      activation and effector-memory, respectively. CD4(+)NK1.1(+) and CD19(+) B cells
      were decreased in percentage both 6 and 11 weeks after bilateral or unilateral
      injury. There was a significant upregulation of IL-1beta, IL-6, TNF-alpha, IFN
      gamma, MIP-2, and RANTES expression, measured by real-time PCR, 6 weeks after
      unilateral renal ischemia, further indicating T cell activation. Depletion of
      CD4(+) and CD8(+) T cells before ischemia caused less medullary damage and
      reduced kidney IFN-gamma expression, whereas their depletion following ischemia
      increased kidney IL-1beta; however, depletion of these cells had no effect on
      histological damage to the kidney. Our study demonstrates that moderate or severe
      kidney ischemia induces long-term T lymphocyte infiltration and
      cytokine/chemokine upregulation, leading to kidney structural changes.

PMID- 19092798
TI  - How does extended lymphadenectomy influence practical care for patients with
      gastric cancer?
AB  - The recurrence and survival rates in patients with curable gastric cancer remain
      suboptimal. Debate on the optimal extent of lymphadenectomy for the surgical
      treatment of these patients is, therefore, still ongoing. A randomized,
      controlled trial by Sasako et al. has examined whether addition of para-aortic
      nodal dissection to D2 lymphadenectomy improves survival in patients with gastric
      cancer. The study included 523 patients who were randomly assigned either D2
      lymphadenectomy or D2 lymphadenectomy and para-aortic nodal dissection. The
      results from this trial, whose primary end point was overall survival,
      demonstrated no additional benefit of lymphadenectomy beyond D2 resection.
      Management strategies should focus on optimal lymphadenectomy in high-volume
      hospitals, with evaluation of chemotherapy and radiotherapy, to achieve low
      surgery-related morbidity and mortality, optimal locoregional control and
      improved survival rates for patients with curable gastric cancer.

PMID- 19092797
TI  - Accelerated development of collapsing glomerulopathy in mice congenic for the
      HIVAN1 locus.
AB  - HIV-1 transgenic mice on the FVB/NJ background (TgFVB) are a well validated model
      of HIV-associated nephropathy (HIVAN). A mapping study between TgFVB and CAST/EiJ
      (CAST) strains showed this trait to be influenced by a major susceptibility locus
      on chromosome 3A1-A3 (HIVAN1), with CAST alleles associated with increased risk
      of disease. We introgressed a 50 Mb interval, encompassing this HIVAN1 locus,
      from CAST into the TgFVB genome (TgFVB-HIVAN1(CAST) congenic mice). Compared to
      the TgFVB strain, these congenic mice developed an earlier onset of proteinuria,
      a rapid progression to kidney failure, and increased mortality. A prospective
      study of these congenic mice also showed that they had a significantly greater
      histologic and biochemical evidence of glomerulopathy with one-third of mice
      developing global glomerulosclerosis by 6 weeks of age. An F2 cross between TgFVB
      and the congenic mice identified a significant linkage (LOD=3.7) to a 10 cM
      interval within the HIVAN1 region between D3Mit167 and D3Mit67 resulting in a 60%
      reduction of the original interval. These data independently confirm that a gene
      on chromosome 3A1-A3 increases susceptibility to HIVAN, resulting in early onset
      and rapid progression of kidney disease. These mice represent a new model to
      study the development and progression of collapsing glomerulopathy.

PMID- 19092799
TI  - Which questions remain unanswered following the successful development of
      sorafenib in hepatocellular carcinoma?
AB  - Investigation of the effects of various antiangiogenic agents in the therapy of
      solid tumors has been a dominant theme in oncology for the past decade.
      Hepatocellular carcinoma has joined the short list of tumor types for which
      single-agent antiangiogenic therapy has shown clear clinical benefit. Here we
      discuss the findings of a multicenter, phase III trial by Llovet et al., which
      compared overall survival, time to symptomatic progression, and time to
      radiologic progression in 602 patients with hepatocellular carcinoma who received
      either sorafenib (n= 299) or placebo (n = 303). This study showed that patients
      treated with sorafenib had approximately 3 months longer overall survival and
      time to radiologic progression compared with patients who received placebo. For
      optimal clinical application, elucidation of the tumor-specific and patient
      specific factors that identify the subpopulation of patients with hepatocellular
      carcinoma who will derive the greatest benefit from antiangiogenic therapies such
      as sorafenib is of critical importance.

PMID- 19092800
TI  - Does pegylated interferon alpha-2b confer additional benefit in the adjuvant
      treatment of high-risk melanoma?
AB  - High-dose interferon (IFN)alpha-2b has shown benefits in the adjuvant treatment
      of melanoma, but relapse-free and overall survival remain poor, despite the use
      of chemotherapy, vaccines, and combinations of these modalities. Questions remain
      in relation to the relative importance of dose, route and duration of
      immunotherapy needed to prevent relapse and improve survival. Our understanding
      of STAT signaling, the role of dendritic and T cells and of circulating cytokine
      profiles in this benefit of IFN therapy have yet to be deployed clinically. The
      EORTC 18991 trial analyzed whether pegylated IFNalpha-2b delivered for up to 5
      years could improve tolerability and efficacy of IFN. The study demonstrated an
      improvement in a subset of patients with microscopic disease, but not in those
      with gross nodal involvement. The potential role of this agent needs to be
      examined in relation to the long-term control of relapse. Assessment of the
      molecular, immunological, and antiangiogenic effects of the various forms of
      pegylated IFN will be critical to identification of the best future applications
      for these modalities.

PMID- 19092801
TI  - Intermittent targeting as a tool to minimize toxicity of tyrosine kinase
      inhibitor therapy.
AB  - Tyrosine kinase inhibitor therapy has revolutionized the outcome of chronic
      myeloid leukemia (CML), and has transformed a fatal disease into a chronic
      condition for most patients. At present, the therapeutic armamentarium against
      CML includes imatinib for newly diagnosed patients, and dasatinib and nilotinib,
      which have both received marketing approval, for imatinib-resistant and imatinib
      intolerant disease. Research efforts are now focused on how to optimize
      therapeutic strategies in an attempt to improve clinical results further,
      counteract the development of drug resistance and reduce adverse effects. A
      randomized, international, phase III study of dasatinib dose and schedule
      optimization in imatinib-resistant and imatinib-intolerant patients with CML has
      demonstrated that intermittent target inhibition can preserve therapeutic
      efficacy and reduce toxicity. This finding has important implications, not only
      for patients with CML, but also for the development of targeted therapies for
      human malignancies in general.

PMID- 19092802
TI  - WSTF regulates the H2A.X DNA damage response via a novel tyrosine kinase
      activity.
AB  - DNA double-stranded breaks present a serious challenge for eukaryotic cells. The
      inability to repair breaks leads to genomic instability, carcinogenesis and cell
      death. During the double-strand break response, mammalian chromatin undergoes
      reorganization demarcated by H2A.X Ser 139 phosphorylation (gamma-H2A.X).
      However, the regulation of gamma-H2A.X phosphorylation and its precise role in
      chromatin remodelling during the repair process remain unclear. Here we report a
      new regulatory mechanism mediated by WSTF (Williams-Beuren syndrome transcription
      factor, also known as BAZ1B)-a component of the WICH complex (WSTF-ISWI ATP
      dependent chromatin-remodelling complex). We show that WSTF has intrinsic
      tyrosine kinase activity by means of a domain that shares no sequence homology to
      any known kinase fold. We show that WSTF phosphorylates Tyr 142 of H2A.X, and
      that WSTF activity has an important role in regulating several events that are
      critical for the DNA damage response. Our work demonstrates a new mechanism that
      regulates the DNA damage response and expands our knowledge of domains that
      contain intrinsic tyrosine kinase activity.

PMID- 19092803
TI  - The DNA-encoded nucleosome organization of a eukaryotic genome.
AB  - Nucleosome organization is critical for gene regulation. In living cells this
      organization is determined by multiple factors, including the action of chromatin
      remodellers, competition with site-specific DNA-binding proteins, and the DNA
      sequence preferences of the nucleosomes themselves. However, it has been
      difficult to estimate the relative importance of each of these mechanisms in
      vivo, because in vivo nucleosome maps reflect the combined action of all
      influencing factors. Here we determine the importance of nucleosome DNA sequence
      preferences experimentally by measuring the genome-wide occupancy of nucleosomes
      assembled on purified yeast genomic DNA. The resulting map, in which nucleosome
      occupancy is governed only by the intrinsic sequence preferences of nucleosomes,
      is similar to in vivo nucleosome maps generated in three different growth
      conditions. In vitro, nucleosome depletion is evident at many transcription
      factor binding sites and around gene start and end sites, indicating that
      nucleosome depletion at these sites in vivo is partly encoded in the genome. We
      confirm these results with a micrococcal nuclease-independent experiment that
      measures the relative affinity of nucleosomes for approximately 40,000 double
      stranded 150-base-pair oligonucleotides. Using our in vitro data, we devise a
      computational model of nucleosome sequence preferences that is significantly
      correlated with in vivo nucleosome occupancy in Caenorhabditis elegans. Our
      results indicate that the intrinsic DNA sequence preferences of nucleosomes have
      a central role in determining the organization of nucleosomes in vivo.

PMID- 19092804
TI  - Crypt stem cells as the cells-of-origin of intestinal cancer.
AB  - Intestinal cancer is initiated by Wnt-pathway-activating mutations in genes such
      as adenomatous polyposis coli (APC). As in most cancers, the cell of origin has
      remained elusive. In a previously established Lgr5 (leucine-rich-repeat
      containing G-protein-coupled receptor 5) knockin mouse model, a tamoxifen
      inducible Cre recombinase is expressed in long-lived intestinal stem cells. Here
      we show that deletion of Apc in these stem cells leads to their transformation
      within days. Transformed stem cells remain located at crypt bottoms, while
      fuelling a growing microadenoma. These microadenomas show unimpeded growth and
      develop into macroscopic adenomas within 3-5weeks. The distribution of Lgr5(+)
      cells within stem-cell-derived adenomas indicates that a stem cell/progenitor
      cell hierarchy is maintained in early neoplastic lesions. When Apc is deleted in
      short-lived transit-amplifying cells using a different cre mouse, the growth of
      the induced microadenomas rapidly stalls. Even after 30weeks, large adenomas are
      very rare in these mice. We conclude that stem-cell-specific loss of Apc results
      in progressively growing neoplasia.

PMID- 19092805
TI  - Prominin 1 marks intestinal stem cells that are susceptible to neoplastic
      transformation.
AB  - Cancer stem cells are remarkably similar to normal stem cells: both self-renew,
      are multipotent and express common surface markers, for example, prominin 1
      (PROM1, also called CD133). What remains unclear is whether cancer stem cells are
      the direct progeny of mutated stem cells or more mature cells that reacquire stem
      cell properties during tumour formation. Answering this question will require
      knowledge of whether normal stem cells are susceptible to cancer-causing
      mutations; however, this has proved difficult to test because the identity of
      most adult tissue stem cells is not known. Here, using an inducible Cre, nuclear
      LacZ reporter allele knocked into the Prom1 locus (Prom1(C-L)), we show that
      Prom1 is expressed in a variety of developing and adult tissues. Lineage-tracing
      studies of adult Prom1(+/C-L) mice containing the Rosa26-YFP reporter allele
      showed that Prom1(+) cells are located at the base of crypts in the small
      intestine, co-express Lgr5 (ref. 2), generate the entire intestinal epithelium,
      and are therefore the small intestinal stem cell. Prom1 was reported recently to
      mark cancer stem cells of human intestinal tumours that arise frequently as a
      consequence of aberrant wingless (Wnt) signalling. Activation of endogenous Wnt
      signalling in Prom1(+/C-L) mice containing a Cre-dependent mutant allele of beta
      catenin (Ctnnb1(lox(ex3))) resulted in a gross disruption of crypt architecture
      and a disproportionate expansion of Prom1(+) cells at the crypt base. Lineage
      tracing demonstrated that the progeny of these cells replaced the mucosa of the
      entire small intestine with neoplastic tissue that was characterized by focal
      high-grade intraepithelial neoplasia and crypt adenoma formation. Although all
      neoplastic cells arose from Prom1(+) cells in these mice, only 7% of tumour cells
      retained Prom1 expression. Our data indicate that Prom1 marks stem cells in the
      adult small intestine that are susceptible to transformation into tumours
      retaining a fraction of mutant Prom1(+) tumour cells.

PMID- 19092806
TI  - Quality control by the ribosome following peptide bond formation.
AB  - The overall fidelity of protein synthesis has been thought to rely on the
      combined accuracy of two basic processes: the aminoacylation of transfer RNAs
      with their cognate amino acid by the aminoacyl-tRNA synthetases, and the
      selection of cognate aminoacyl-tRNAs by the ribosome in cooperation with the
      GTPase elongation factor EF-Tu. These two processes, which together ensure the
      specific acceptance of a correctly charged cognate tRNA into the aminoacyl (A)
      site, operate before peptide bond formation. Here we report the identification of
      an additional mechanism that contributes to high fidelity protein synthesis after
      peptidyl transfer, using a well-defined in vitro bacterial translation system. In
      this retrospective quality control step, the incorporation of an amino acid from
      a non-cognate tRNA into the growing polypeptide chain leads to a general loss of
      specificity in the A site of the ribosome, and thus to a propagation of errors
      that results in abortive termination of protein synthesis.

PMID- 19092811
TI  - Spatial distribution of coronary artery thromboses in patients with chronic
      kidney disease: implications for diagnosis and treatment.
AB  - The study by Charytan et al. provides us with a better understanding of the
      pathophysiology of acute myocardial infarction in patients with chronic kidney
      disease (CKD). One important observation is that more proximal plaque rupture
      results in poorer outcome in patients with CKD; clinicians should target these
      patients for aggressive revascularization to try to improve outcomes. This study
      will hopefully lead to additional research and help us develop more effective
      local and systemic therapies for patients with CKD.

PMID- 19092807
TI  - Peptide neurotransmitters activate a cation channel complex of NALCN and UNC-80.
AB  - Several neurotransmitters act through G-protein-coupled receptors to evoke a
      'slow' excitation of neurons. These include peptides, such as substance P and
      neurotensin, as well as acetylcholine and noradrenaline. Unlike the fast
      (approximately millisecond) ionotropic actions of small-molecule
      neurotransmitters, the slow excitation is not well understood at the molecular
      level, but can be mainly attributed to suppressing K(+) currents and/or
      activating a non-selective cation channel. The molecular identity of this cation
      channel has yet to be determined; similarly, how the channel is activated and its
      relative contribution to neuronal excitability induced by the neuropeptides are
      unknown. Here we show that, in the mouse hippocampal and ventral tegmental area
      neurons, substance P and neurotensin activate a channel complex containing NALCN
      and a large previously unknown protein UNC-80. The activation by substance P
      through TACR1 (a G-protein-coupled receptor for substance P) occurs by means of a
      unique mechanism: it does not require G-protein activation but is dependent on
      Src family kinases. These findings identify NALCN as the cation channel activated
      by substance P receptor, and suggest that UNC-80 and Src family kinases, rather
      than a G protein, are involved in the coupling from receptor to channel.

PMID- 19092812
TI  - The new role of calcimimetics as vasculotropic agents.
AB  - The discovery of the calcium-sensing receptor (CaSR) and the development of
      calcimimetics have provided new insights into calcium homeostasis and new
      therapeutic opportunities for parathyroid-related disorders. However, the CaSR is
      also implicated in various other cellular processes, and the translational
      applications of calcimimetics may not be exclusively calcium-centric. Koleganova
      et al. describe a novel role for calcimimetics as vasculotropes, which provides
      the impetus for further studies to characterize their effects on vascular
      biology.

PMID- 19092813
TI  - Inhibition of the renin-angiotensin system: is more better?
AB  - Inhibitors of the renin-angiotensin-aldosterone system (RAS) exert beneficial
      effects in diabetic nephropathy, but the possibility of regression of existing
      renal lesions remains to be investigated. Teles et al. tested the effects of the
      RAS inhibitor losartan in rats starting 10 months after induction of diabetes,
      when glomerular lesions were already present. They linked the reductions of
      proteinuria with regression of mesangial expansion. More advanced lesions were
      not affected. There were no dose-response renal effects of losartan.

PMID- 19092814
TI  - A calcimimetic (R-568), but not calcitriol, prevents vascular remodeling in
      uremia.
AB  - Renal insufficiency increases cardiovascular risk, accelerates atherogenesis, and
      causes vascular wall remodeling. Here we evaluated the effect of the calcimimetic
      R-568 and non-hypercalcemic doses of calcitriol on vascular structure. Subtotal
      nephrectomy was produced in Sprague-Dawley rats followed by treatment with R-568,
      calcitriol, or vehicle for 12 weeks. The aortic wall was significantly thicker in
      vehicle-treated uremic rats than in those with a sham-operation but R-568-treated
      uremic rats had a lower value. In contrast, calcitriol increased wall thickness
      in both the sham-operated and uremic groups. The calcification score, measured by
      von Kossa staining, and the number of proliferating cells in the intima and media
      were significantly higher in the calcitriol-treated uremic group. The expression
      of the calcium sensing receptor was higher in the intima of sham-operated and
      uremic rats treated with R-568 compared to animals treated with vehicle or
      calcitriol, while the expression of the vitamin D receptor was upregulated by
      both calcitriol and R-568. Our study shows that in uremic rats, calcitriol
      increased while R-568 attenuated media calcification and proliferation of
      vascular smooth muscle and endothelial cells.

PMID- 19092815
TI  - Elevated urine neutrophil gelatinase-associated lipocalin can diagnose acute
      kidney injury in patients with chronic kidney diseases.

PMID- 19092817
TI  - Does postmenopausal hormone therapy influence renal function?

PMID- 19092818
TI  - Autophagy: a protective mechanism against nephrotoxicant-induced renal injury.

PMID- 19092821
TI  - Telmisartan is more effective than losartan in reducing proteinuria.

PMID- 19092822
TI  - Adiponectin in chronic kidney disease: Dr Jekyll and Mr Hyde.

PMID- 19092827
TI  - The case / a Senegalese man with gross hematuria.

PMID- 19092828
TI  - The yin-yang sign.

PMID- 19092832
TI  - Is denosumab better than alendronate in the treatment of osteoporosis?
AB  - Denosumab is a fully human monoclonal antibody to receptor activator of nuclear
      factor kappaB ligand (RANKL), the principal mediator of osteoclastic bone
      resorption. By binding to RANKL, denosumab reduces the differentiation, activity
      and survival of osteoclasts, and thereby slows the rate of bone resorption. These
      antiresorptive effects led to the development of this agent as a treatment for
      osteoporosis. In studies conducted so far, denosumab is an efficacious and well
      tolerated treatment for postmenopausal osteoporosis. Oral bisphosphonates are
      currently favored as first-line therapy for most patients with this condition
      and, therefore, studies that directly compare the effects of these agents with
      denosumab are of clinical interest. Here, I discuss a study by Brown et al. that
      compares the effects of denosumab and alendronate in women who have not
      previously received antiosteoporosis therapy, and place the findings in the
      context of other clinically relevant studies of this RANKL inhibitor.

PMID- 19092831
TI  - Anti-CD20 antibody is an efficient therapeutic tool for the selective removal of
      autoreactive T cells.

PMID- 19092833
TI  - Is there a role for everolimus in the treatment of RA?
AB  - The past decade has seen remarkable advances in the treatment of rheumatoid
      arthritis. Although this is good news for the majority of patients, one
      consequence is that the environment for the development of new drugs has become
      difficult as a result of high expectations for efficacy. Nevertheless, there
      remains a subgroup of patients with rheumatoid arthritis who are not candidates
      for treatment with the newer biologic agents and in whom oral DMARDs have certain
      advantages. A recent report by Bruyn et al. suggests that the proliferation
      signal inhibitor everolimus could have unique properties, in addition to a
      convenient once-daily oral dosing schedule, that might fit this niche in the
      therapeutic armamentarium. Further studies are required, however, to confirm the
      disease-modifying effects and adverse event profile of this drug.

PMID- 19092834
TI  - What have nephrologists and cardiologists learnt from each other?

PMID- 19092836
TI  - Integrative biology--a strategy for systems biomedicine.
AB  - The precision of genome sequences, together with advanced computational
      approaches, allows complex, clinically relevant biological systems to be
      examined. Here, I describe the experiences of the Genome Institute of Singapore
      (GIS) in using genome-to-systems strategies to accelerate biomedical research. To
      maximize clinically relevant output, we have explored an organizational strategy
      that encourages coordinated experimentation among investigators with diverse
      skills and interests through building a culture of integrative science. Our
      experience suggests that systems biomedicine is a real and potentially fruitful
      strategy for translational research.

PMID- 19092837
TI  - Informed consent for penile prosthesis.

PMID- 19092838
TI  - Preputial graft in penile curvature correction: preliminary results.
AB  - Our purpose is to assess efficacy and complications of preputial skin graft for
      treatment of penile curvatures by grafting corporoplasty. Five congenital
      curvature and 14 Peyronie's disease patients were treated by grafting
      corporoplasty using preputial skin. Patients were evaluated by medical history
      and International Index of Erectile Function-5 (IIEF-5) questionnaire. After
      injection-induced erection, patients were evaluated by penile length measurement
      and color Duplex. Patients were re-evaluated 1 month later and advised to start
      intercourse. Patients were also evaluated during the 3rd and 12th months
      postoperatively, as per the original protocol. By the end of the follow-up
      period, 75% of patients were satisfied with straightened penises, without
      dilatation of the graft (ballooning) or venous leakage. Patients also exhibited a
      mean increase of two units in IIEF-5 score. Penile straightening and satisfaction
      rate were lower in the remaining 25% of patients, but no complaints of worsening
      erection or bulging of the graft area were reported. Preputial graft is an
      inexpensive procedure involving a tissue familiar to the urologist. The results
      of grafting corporoplasty are promising, without significant complications.

PMID- 19092835
TI  - Detecting shared pathogenesis from the shared genetics of immune-related
      diseases.
AB  - Recent genetic studies have revealed shared immunological mechanisms in several
      immune-related disorders that further our understanding of the development and
      concomitance of these diseases. Our Review focuses on these shared aspects, using
      the novel findings of recently performed genome-wide association studies and non
      synonymous SNP scans as a starting point. We discuss how identifying new genes
      that are associated with more than one autoimmune or chronic inflammatory
      disorder could explain the genetic basis of the shared pathogenesis of immune
      related diseases. This analysis helps to highlight the key molecular pathways
      that are involved in these disorders and the potential roles of novel genes in
      immune-related diseases.

PMID- 19092839
TI  - Hematologic effects of placental pathology on very low birthweight infants born
      to mothers with preeclampsia.
AB  - OBJECTIVE: To investigate the effect of placental pathology on neonatal
      neutrophils, platelets, hematocrit and nucleated red blood cells in very low
      birthweight (VLBW) infants born to mothers with preeclampsia. STUDY DESIGN:
      Retrospective cohort study of infants with birthweight < 1500 g born to mothers
      with preeclampsia from july, 2002 to july, 2006 at a single level III neonatal
      intensive care unit. Placental pathology was reviewed for the presence of
      placental infarction and vasculopathy. Hematologic parameters from day of life 0,
      1 and 2 were obtained. Statistical analysis included repeated-measures analysis
      of variance and multivariable analysis using logistic regression. RESULT: The
      study sample included 203 infants with estimated gestational age of 28+/-3 weeks;
      45% had placental infarctions and 26% placental vasculopathy. Infants with
      neutropenia and thrombocytopenia did not have an increased occurrence of
      placental infarction or maternal vasculopathy but were more likely to be of small
      gestational age (SGA) and of lower gestational age compared with infants without
      neutropenia or thrombocytopenia. After multivariable analysis, gestational age
      and SGA remained associated with both neutropenia and thrombocytopenia whereas
      placental infarction and vasculopathy did not remain in the models. CONCLUSION:
      In our population of VLBW infants born to mothers with preeclampsia, placental
      pathology was common. There was no association of placental infarction or
      vasculopathy with neonatal neutropenia and thrombocytopenia. The data suggest
      that neonatal hematologic effects of maternal preeclampsia, if related to the
      placenta, are associated with factors other than placental histology.

PMID- 19092840
TI  - Replication of the TNFSF4 (OX40L) promoter region association with systemic lupus
      erythematosus.
AB  - The tumor necrosis factor ligand superfamily member 4 gene (TNFSF4) encodes the
      OX40 ligand (OX40L), a costimulatory molecule involved in T-cell activation. A
      recent study demonstrated the association of TNFSF4 haplotypes located in the
      upstream region with risk for or protection from systemic lupus erythematosus
      (SLE). To replicate this association, five single nucleotide polymorphisms (SNPs)
      tagging the previously associated haplotypes and passing the proper quality
      control filters were tested in 1312 cases and 1801 controls from Germany, Italy,
      Spain and Argentina. The association of TNFSF4 with SLE was replicated in all the
      sets except Spain. There was a unique risk haplotype tagged by the minor alleles
      of the SNPs rs1234317 (pooled odds ratio (OR)=1.39, P=0.0009) and rs12039904
      (pooled OR=1.38, P=0.0012). We did not observe association to a single protective
      marker (rs844644) or haplotype as the first study reported; instead, we observed
      different protective haplotypes, all carrying the major alleles of both SNPs
      rs1234317 and rs12039904. Association analysis conditioning on the haplotypic
      background confirmed that these two SNPs explain the entire haplotype effect.
      This first replication study confirms the association of genetic variation in the
      upstream region of TNFSF4 with susceptibility to SLE.

PMID- 19092841
TI  - Expression analysis and functional activity of interleukin-7 splice variants.
AB  - Alternative splicing results in multiple protein isoforms derived from a single
      gene. The magnitude of this process ranges from a complete loss of function to
      gain of new function. We examined, as a paradigm, alternative splicing of the non
      redundant human cytokine, interleukin-7 (IL-7). We show that extensive IL-7
      splicing in human tissues of different histology, including MTB+ granuloma
      lesions, transformed tissue and tumor cell lines. IL-7 splice variants were
      expressed as recombinant proteins. A differentially spliced IL-7 isoform, lacking
      exon 5, leads to STAT-5 phosphorylation in CD4+ and CD8+ T cells, promotes
      thymocyte maturation and T-cell survival. Human tumor lesions show aberrant IL-7
      isoform expression, as compared with the autologous, non-transformed tissue.
      Alternatively spliced cytokines, such as IL-7, represent candidates for
      diagnostics and therapeutic interventions.

PMID- 19092842
TI  - Additive effects of the major risk alleles of IRF5 and STAT4 in primary Sjogren's
      syndrome.
AB  - Primary Sjogren's syndrome (SS) shares many features with systemic lupus
      erythematosus (SLE). Here we investigated the association of the three major
      polymorphisms in IRF5 and STAT4 found to be associated with SLE, in patients from
      Sweden and Norway with primary SS. These polymorphisms are a 5-bp CGGGG indel in
      the promoter of IRF5, the single nucleotide polymorphism (SNP) rs10488631
      downstream of IRF5 and the STAT4 SNP rs7582694, which tags the major risk
      haplotype of STAT4. We observed strong signals for association between all three
      polymorphisms and primary SS, with odds ratios (ORs) >1.4 and P-values <0.01. We
      also found a strong additive effect of the three risk alleles of IRF5 and STAT4
      with an overall significance between the number of risk alleles and primary SS of
      P=2.5 x 10(-9). The OR for primary SS increased in an additive manner, with an
      average increase in OR of 1.78. For carriers of two risk alleles, the OR for
      primary SS is 1.43, whereas carriers of five risk alleles have an OR of 6.78.
      IRF5 and STAT4 are components of the type I IFN system, and our findings
      emphasize the importance of this system in the etiopathogenesis of primary SS.

PMID- 19092843
TI  - The impact of pulse pressure on the accuracy of wrist blood pressure measurement.
AB  - There is an increasing number of wrist blood pressure measurement devices that
      successfully passed the validation procedures of the British Hypertension Society
      (BHS) and the European Society of Hypertension (ESH). It remains unknown,
      however, whether pulse pressure as a marker of arterial stiffness and vascular
      ageing affects the accuracy of these devices. An ESH protocol validated wrist
      device was compared with the upper arm mercury sphygmomanometry in a study
      population (33 patients, 99 measurements) including a relevant number of subjects
      with pulse pressure >50 mm Hg (84.8%) and isolated systolic hypertension (27.3%).
      Mean systolic bias was 10.2 mm Hg with 95% limits of agreement of -13.1 and 33.6
      mm Hg, mean diastolic bias was 4.8 mm Hg with limits of agreement of -11.0 and
      20.7 mm Hg. The impact of body mass index, age, systolic blood pressure and pulse
      pressure on the absolute value of blood pressure bias was tested by stepwise
      multiple regression analysis. The systolic bias significantly depended on pulse
      pressure, whereas there was no significant effect of the independent variables on
      the diastolic bias. Separate correlation analysis showed a significant
      correlation between pulse pressure and both absolute systolic bias (Pearson
      r=0.48, P<0.001) and relative systolic bias (systolic bias divided by systolic
      blood pressure, Pearson r=0.29, P=0.003). Even well-validated wrist blood
      pressure devices can show a clinically relevant bias in patients with elevated
      pulse pressure. Increased arterial stiffness may impair the accuracy of
      oscillometric blood pressure measurement at the wrist.

PMID- 19092844
TI  - Dietary intake, blood pressure and osteoporosis.
AB  - Both hypertension and osteoporosis have common underlying nutritional aetiology,
      with regards to dietary cations intake. We tested the hypothesis that sodium
      intake reflected in urinary Na/Cr and blood pressure would be negatively
      associated with bone mineral density (BMD), whereas other cations may have
      opposite associations. Subjects were part of a study of bone health in 4000 men
      and women aged 65 years and over. A total of 1098 subjects who were not on
      antihypertensive drugs or calcium supplements and who provided urine samples were
      available for analysis. Logistic regression was used to examine associations
      between total hip and lumbar spine BMD, age, gender, body mass index (BMI),
      urinary Na/Cr, K/Cr, calcium and magnesium intake, systolic blood pressure and
      diastolic blood pressure. Total hip BMD was inversely associated with age, being
      female and urinary Na/Cr, and positively associated with BMI, urine K/Cr and
      dietary calcium intake. Lumbar spine BMD was inversely associated with being
      female and urinary Na/Cr, and positively associated with BMI, dietary calcium
      intake and SBP. We conclude that sodium intake, reflected by urinary Na/Cr, is
      the major factor linking blood pressure and osteoporosis as shown by the inverse
      relationship with BMD. The findings lend further emphasis to the health benefits
      of salt reduction in our population both in terms of hypertension and
      osteoporosis.

PMID- 19092845
TI  - Lifestyle factors are determinants of children's blood pressure levels: the
      CYKIDS study.
AB  - Elevated blood pressure (BP) levels represent an important risk factor for
      cardiovascular disease. Lifestyle factors associated with increased BP levels
      have been extensively investigated in adults, but not in children. Therefore, we
      aimed to explore associations among modifiable lifestyle and levels of BP in 10-
      to13-year-old children. A subsample of the CYKIDS (CYprus KIDS) national cross
      sectional study consisting of 622 children (11.7+/-0.83 years) was used to
      evaluate the research hypothesis. Measurements included BP, height, weight and
      waist circumference. Body mass index (BMI) was calculated according to the
      International Obesity Task Force (IOTF) criteria. Adherence to the Mediterranean
      diet was assessed by the KIDMED (Mediterranean Diet Quality Index for children
      and adolescents) diet score, whereas physical activity was assessed through a
      physical activity index. Results have shown that the cutoff value of 120/80 mm Hg
      was significantly associated with various lifestyle indices. BMI was positively
      associated with systolic BP (SBP)>120 mm Hg (odds ratio (OR)=1.21, 95% confidence
      interval (CI) 1.11-1.32); diastolic BP (DBP)>80 mm Hg (OR=1.13, 95% CI 1.01-1.27)
      and SBP/DBP>120/80 mm Hg (OR=1.20, 95% CI 1.10-1.31). Moreover, children who
      reported that they frequently eat while watching television were about two times
      more likely to have elevated SBP or overall BP, whereas children with low
      socioeconomic status levels were more than 2.5 times more likely to have elevated
      BP levels. Finally, compared with those with low KIDMED score, children with at
      least an average [corrected] score were 75% less likely to have elevated DBP
      levels, whereas they exhibited a nonsignificant trend for lower SBP (by 29%) and
      lower overall BP levels (by 30%). Similar results emerged when the above analyses
      were repeated using the American reference values. Conclusively, our study
      suggests that lifestyle factors play an important role in determining BP levels
      in children; a finding that underlines the importance of lifestyle modifications
      in children.

PMID- 19092847
TI  - Effects of muscle contraction timing during resistance training on vascular
      function.
AB  - Muscle contractions in normal resistance training are performed by eccentric
      (ECC, lowering phase) and concentric (CON, lifting phase) muscle contractions.
      However, the difference in effects of timing of muscle contraction during
      resistance training on arterial stiffness is unknown. This study investigated the
      effect of muscle contraction timing during resistance training on vascular
      function in healthy young adults. Thirty healthy men were randomly assigned to
      group of resistance training with quick lifting and slow lowering (ERT, n=10),
      group of resistance training with slow lifting and quick lowering (CRT, n=10) and
      sedentary groups (SED, n=10). The ERT and CRT groups underwent two supervised
      resistance-training sessions per week for 10 weeks. The ERT group performed the
      on set of 8-10 repetitions with 3 s ECC and 1 s CON muscle contractions. In
      contrast, the CRT group performed the on set of 8-10 repetitions with 1 s ECC and
      3 s CON muscle contractions. Brachial-ankle pulse wave velocity (baPWV) after ERT
      did not change from baseline. In contrast, baPWV after CRT increased from
      baseline (from 1049+/-37 to 1153+/-30 cm s(-1), P<0.05). No significant changes
      in flow-mediated dilation were observed in the ERT and CRT groups. These values
      did not change in the SED group. These findings suggest that although both
      training does not deteriorate a vascular endothelial function, resistance
      training with quick lifting and slow lowering (that is, ERT) prevent the
      stiffening of arterial stiffness.

PMID- 19092846
TI  - High blood pressure in middle age is associated with a future decline in
      activities of daily living. NIPPON DATA80.
AB  - Although several studies have reported on the relation between high blood
      pressure (BP) and impaired activities of daily living (ADL), only a few studies
      have reported on the relation of high BP in middle-aged subjects with future
      impaired ADL. Furthermore, no studies reported an excess impaired ADL due to non
      normal BP. Using ADL 1999 data, we compared data from NIPPON DATA80 survivors
      without impaired ADL (N=1816) with those with impaired ADL (N=75) using baseline
      BP information collected in 1980. We analysed participants who were aged 47-59
      years at baseline. Multiple adjusted logistic regression analyses were used to
      estimate the risk of impaired ADL, according to baseline BP categories using
      Joint National Committee 7 guidelines (normal BP, prehypertension, stage 1
      hypertension (HT) and stage 2 HT). Subjects who used antihypertensive medications
      were classified as having stage 2 HT. We calculated excess impaired ADL due to
      non-normal BP. Compared with normal BP categories, the adjusted odds ratio (OR)
      and 95% confidence interval (CI) of having impaired ADL was higher in subjects
      with prehypertension (OR=1.50, 95% CI: 0.55-4.09), stage 1 HT (OR=1.56, 95% CI:
      0.56-4.32) and stage 2 HT (OR=2.96, 95% CI: 1.09-8.05). Non-normal BP explained
      45% (33.7/75) of impaired ADL. A positive relation of BP categories with the
      composite end point of mortality and impaired ADL was also observed. In
      conclusion, controlling BP in middle age may prevent deaths and future ADL
      decline.

PMID- 19092848
TI  - Gene expression profiles in differentiating leukemia cells induced by methyl
      jasmonate are similar to those of cytokinins and methyl jasmonate analogs induce
      the differentiation of human leukemia cells in primary culture.
AB  - Jasmonates are potent lipid regulators in plants that play pivotal roles in their
      biological activities. Methyl jasmonate (MJ) is very effective at inducing the
      myelomonocytic differentiation of human myeloid leukemia HL-60 cells. We examined
      the gene expression profiles associated with exposure to MJ using cDNA
      microarrays, and compared the results with those obtained with other inducers of
      differentiation, such as all-trans retinoic acid (ATRA), 1alpha,25
      dihydroxyvitamin D(3) (VD(3)), isopentenyladenine (IPA) and cotylenin A (CN-A).
      Many genes were upregulated, and only a small fraction was downregulated, upon
      exposure to the inducers. MJ, IPA and CN-A, but not ATRA or VD(3), immediately
      induced the expression of mRNA for the calcium-binding protein S100P. The gene
      expression profile induced by MJ resembled that induced by IPA, suggesting that
      these inducers share many common signal transduction systems for inducing the
      differentiation of leukemia cells. Methyl 4,5-didehydrojasmonate was about 30
      times more potent than MJ and the natural form of the stereoisomer was more
      effective than the unnatural isomer. It significantly stimulated both the
      functional and morphological differentiation of leukemia cells that had been
      freshly isolated from patients with hematological malignancies. Jasmonate
      derivatives may be promising therapeutic agents for differentiation therapy of
      leukemia.

PMID- 19092849
TI  - Inhibition of constitutive and BCR-induced Syk activation downregulates Mcl-1 and
      induces apoptosis in chronic lymphocytic leukemia B cells.
AB  - The protein kinase Syk is a key mediator of proximal B-cell receptor (BCR)
      signaling. Following antigen stimulation, Syk is recruited to the BCR and becomes
      activated by phosphorylation at Y352. Recently, Syk was found to be
      constitutively phosphorylated in several common B-cell lymphoma subtypes,
      indicating a role for antigen-independent Syk activation in the pathogenesis of
      these diseases. We now report that Syk is constitutively phosphorylated on the
      activating Y352 residue in chronic lymphocytic leukemia (CLL) B cells. To examine
      the effects of constitutive Syk activity on intracellular signaling and leukemic
      cell survival, we performed in vitro studies with the Syk inhibitor R406.
      Treatment with R406 induced leukemic cell apoptosis in the majority of
      investigated cases and affected the basal activity or expression of several pro
      survival molecules regulated by Syk, including the Akt and extracellular signal
      regulated (ERK) kinases, and the anti-apoptotic protein Mcl-1. In addition, R406
      prevented the increase in leukemic cell viability induced by sustained BCR
      engagement and inhibited BCR-induced Akt activation and Mcl-1 upregulation.
      Collectively, these data identify Syk as a potential target for CLL treatment and
      suggest that inhibition of this kinase could provide a double therapeutic benefit
      by disrupting both antigen-dependent and antigen-independent signaling pathways
      that regulate leukemic cell survival.

PMID- 19092850
TI  - Role of catalase in monocytic differentiation of U937 cells by TPA: hydrogen
      peroxide as a second messenger.
AB  - Human promonocytic cell line U937 cells can be induced to differentiate into
      macrophages by treatment with 12-O-tetradecanoylphorbol-13-acetate (TPA). TPA
      treatment induced the expression of the monocytic differentiation markers CD11b
      and CD36, with concomitant morphological changes. Moreover, TPA enhanced reactive
      oxygen species (ROS) generation in these cells, and phagocytic ability was also
      stimulated during differentiation. The antioxidant agent N-acetyl-L-cysteine
      inhibited the TPA-induced differentiation of U937 cells. TPA treatment decreased
      the expression level of catalase, which catalyzes the decomposition of hydrogen
      peroxide (H(2)O(2)) to H(2)O and O(2). In contrast, TPA increased the level of
      manganese superoxide dismutase, which catalyzes the dismutation of superoxide
      into H(2)O(2) and O(2) without affecting the levels of copper-zinc superoxide
      dismutase or glutathione peroxidase 1, which removes H(2)O(2) using glutathione
      as substrate. Treatment of U937 cells with catalase inhibited the enhancement of
      ROS generation induced by TPA, and blocked the TPA-induced differentiation of
      U937 cells. Human promyelocytic cell line HL60 cells were also induced to
      differentiate into macrophages by TPA. However, HP100-1 cells, its variant cell
      line overexpressing catalase, were resistant to TPA-induced differentiation. Our
      results suggest that catalase inhibits monocytic differentiation by TPA; the
      decrease in catalase level and the accumulation of H(2)O(2) are significant
      events for monocyte/macrophage differentiation by TPA.

PMID- 19092851
TI  - Therapeutic concentrations of dasatinib inhibit in vitro osteoclastogenesis.

PMID- 19092852
TI  - The candidate immunotherapeutical target, the receptor for hyaluronic acid
      mediated motility, is associated with proliferation and shows prognostic value in
      B-cell chronic lymphocytic leukemia.
AB  - Differential expression of molecules in chronic lymphocytic leukemia (CLL) may
      define prognostic markers and suitable targets for immunotherapy. Expression of
      the tumor-associated antigen (TAA) RHAMM (receptor for hyaluronic acid-mediated
      motility) as well as RHAMM splicing variants was assessed in series of 72 CLL
      patients. Quantitative reverse transcriptase PCR showed higher RHAMM expression
      in high-risk CLL patients, as well as in the advanced stages of the disease. CLL
      cases with a higher RHAMM expression showed a significantly shorter median
      treatment-free survival. Among patients with mutated immunoglobulin heavy chain
      genes, an analysis of RHAMM expression enabled to distinguish subgroup of
      patients with favorable prognosis. In lymph nodes, RHAMM staining correlated with
      a higher Ki-67 index and CD40L expression. Functionally, stimulation with CD40L
      enhanced RHAMM expression in CLL. We further characterized RHAMM-specific CD8(+)
      T cells in patients with CLL, as the expression of TAAs might influence the
      clinical outcome by the means of immune reactions. The cytotoxic potential of
      RHAMM-specific T cells was shown against target cells bearing RHAMM-derived
      epitope as well as against CLL cells expressing RHAMM. In conclusion, RHAMM
      expression appears to be of prognostic value, as well as may reflect the
      proliferative capacity of CLL cells, and might therefore represent interesting
      target for immunotherapy.

PMID- 19092853
TI  - A phase I study of tipifarnib combined with conventional induction and
      consolidation therapy for previously untreated patients with acute myeloid
      leukemia aged 60 years and over.
AB  - Patients aged 60 years and over with previously untreated acute myeloid leukemia
      were enrolled in a Phase I study combining tipifarnib with standard induction
      therapy. The regimen consisted of cytarabine 100 mg/m(2)/day continuous
      intravenous (i.v.) infusion on days 1-7, daunorubicin 60 mg/m(2)/day i.v. push x
      3 on days 6-8 and tipifarnib twice daily on days 6-15. Tipifarnib was escalated
      over four dose levels (200, 300, 400 and 600 mg). Patients achieving complete
      response (CR) were eligible to receive one consolidation using the same regimen.
      The following dose-limiting toxicities (DLTs) were identified during induction:
      dose level I: 2/6 (hyperbilirubinemia, respiratory arrest), level II: 0/3, level
      III: 0/3 and level IV: 4/10 (one each of diarrhea, neutropenic enterocolitis,
      arrhythmia and delayed hematologic recovery post-consolidation). There were no
      DLTs due to delayed hematologic recovery post-induction. Of 22 evaluable
      patients, there were 10 CR, 2 morphologic leukemia-free state (MLFS), 2 partial
      remission (PR) and 8 non-responders. Of seven patients with adverse risk
      cytogenetics, there were four CR/MLFS and one PR. In summary, this regimen was
      well tolerated and the maximum tolerated dose was not reached, although somewhat
      more severe gastrointestinal toxicity was seen at dose level IV. Tipifarnib 600
      mg b.i.d. is considered the recommended dose for further study using this
      regimen.

PMID- 19092854
TI  - CTLA-4 genotype and relapse incidence in patients with acute myeloid leukemia in
      first complete remission after induction chemotherapy.
AB  - The recently described single-nucleotide polymorphism CT60, located in the 3'
      untranslated region of the CTLA4 (cytotoxic T-lymphocyte antigen 4 ) gene, has
      been associated with susceptibility to several autoimmune diseases and has also
      been shown to be involved in immune responses following allogeneic stem cell
      transplantation (SCT). However, the contribution of the CTLA4 genotype to the
      control of minimal residual disease in patients with acute myeloid leukemia (AML)
      has yet to be explored. We investigated the association between the CTLA4 CT60
      A/G genotype and the incidence of leukemic relapse in 143 adult patients with AML
      in first complete remission after the same chemotherapy protocol (CETLAM LAM'03).
      The CT60 AA genotype was associated with a higher rate of leukemic relapse (56.4
      vs 35.6%, P=0.004; hazard ratio (HR)=2.64, 95% confidence interval (CI)=1.36
      5.14) and lower overall survival at 3 years (39.4 vs 68.4%, P=0.004; HR=2.80, 95%
      CI=1.39-5.64). This is the first study to report an association between
      polymorphisms at CTLA-4 and AML relapse.

PMID- 19092855
TI  - Involvement of Tis11b, an AU-rich binding protein, in induction of apoptosis by
      rituximab in B cell chronic lymphocytic leukemia cells.

PMID- 19092856
TI  - Interleukin-6 small interfering RNA improved the herpes simplex virus-induced
      systemic inflammation in vivo Behcet's disease-like mouse model.
AB  - It is known that the level of interleukin-6 (IL-6) is higher in patients with
      active Behcet's disease (BD) than in those with inactive disease. Herpes simplex
      virus (HSV) type 1 inoculation of the earlobes of ICR mice resulted in the
      development of BD-like symptoms. To find out whether downregulation of IL-6 would
      affect the symptoms of BD, IL-6 small interfering RNA (siRNA) was administered to
      a BD mouse model. IL-6 siRNA was intraperitoneally injected into BD mice to
      downregulate IL-6 (n=9). IL-6 siRNA injection downregulated serum IL-6 level
      (118.9+/-114.4 pg ml(-1)) compared with scramble injection (439.4+/-378.0 pg ml(
      1)) in BD mice (P=0.01). In seven out of nine IL-6 siRNA-injected BD mice, 77.8%
      improved and the severity score was decreased from 3.1+/-1.05 to 1.7+/-0.87
      (P=0.005), whereas two out of six (33.3%) scramble-injected BD mice improved and
      the severity score changed from 2.5+/-0.84 to 2.0+/-1.41 (P=0.203). Foxp3, ROR
      gamma t, IL-17A, IL-17F and tumor necrosis factor-alpha were also influenced in
      IL-6 siRNA-injected BD mice compared with scramble-injected BD mice. Adoptive
      transfer of CD4+CD25+ cells to BD mice affected the decrease of IL-6 serum levels
      and were dependent on CD4+CD25+ cell numbers. These results showed that
      downregulation of IL-6 improved the inflammatory symptoms in BD mice through
      upregulation of regulatory T cells and inhibition of Th17 cells.

PMID- 19092857
TI  - A Kunjin replicon vector encoding granulocyte macrophage colony-stimulating
      factor for intra-tumoral gene therapy.
AB  - We have recently developed a non-cytopathic RNA replicon-based viral vector
      system based on the flavivirus Kunjin. Here, we illustrate the utility of the
      Kunjin replicon system for gene therapy. Intra-tumoral injections of Kunjin
      replicon virus-like particles encoding granulocyte colony-stimulating factor were
      able to cure >50% of established subcutaneous CT26 colon carcinoma and B16-OVA
      melanomas. Regression of CT26 tumours correlated with the induction of anti
      cancer CD8 T cells, and treatment of subcutaneous CT26 tumours also resulted in
      the regression of CT26 lung metastases. Only a few immune-based strategies are
      able to cure these aggressive tumours once they are of a reasonable size,
      illustrating the potential of this vector system for intra-tumoral gene therapy
      applications.

PMID- 19092858
TI  - Cellular tropism and transduction properties of seven adeno-associated viral
      vector serotypes in adult retina after intravitreal injection.
AB  - Recombinant adeno-associated virus (rAAV) vectors are increasingly being used as
      tools for gene therapy, and clinical trials have begun in patients with
      genetically linked retinal disorders. Intravitreal injection is optimal for the
      transduction of retinal ganglion cells (RGCs), although complete selectivity has
      not been achieved. There may also be advantages in using intravitreal approaches
      for the transduction of photoreceptors. Here we compared the cellular tropism and
      transduction efficiency of rAAV2/1, -2/2, -2/3, -2/4, -2/5, -2/6 and -2/8 in
      adult rat retina after intravitreal injection. Each vector encoded green
      fluorescent protein (GFP), and the number, laminar distribution and morphology of
      transduced GFP(+) cells were determined using fluorescent microscopy. Assessment
      of transduced cell phenotype was based on cell morphology and
      immunohistochemistry. rAAV2/2 and rAAV2/6 transduced the greatest number of
      cells, whereas rAAV2/5 and rAAV2/8 were least efficient. Most vectors primarily
      transduced RGCs; however, rAAV2/6 had a more diverse tropism profile, with 46%
      identified as amacrine or bipolar cells, 23% as RGCs and 22% as Muller cells.
      Muller cells were also frequently transduced by rAAV2/4. The highest
      photoreceptor transduction was seen after intravitreal rAAV2/3 injection. These
      data facilitate the design and selection of rAAV vectors to target specific
      retinal cells, potentially leading to an improved gene therapy for various human
      retinal pathologies.

PMID- 19092859
TI  - A phase I trial of intratumoral administration of recombinant oncolytic
      adenovirus overexpressing HSP70 in advanced solid tumor patients.
AB  - Our pre-clinical studies demonstrated that intratumoral vaccination with a
      recombinant oncolytic type 2 adenovirus overexpressing the heat shock protein
      (HSP)70 protein, designated as H103, can inhibit primary and metastatic tumors
      through enhanced oncolytic activity and HSP-mediated immune responses against
      shared and mutated tumor antigens. In the pre-clinical studies of local H103
      administration, no significant toxicity was observed in the animal trials with
      mice, cavy or rhesus monkeys. A phase I clinical trial of intratumoral injection
      of H103 was conducted in the patients with advanced solid tumors. A total of 27
      patients were injected intratumorally with H103 in a dose-escalation study from a
      dose of 2.5 x 10(7) to 3.0 x 10(12) viral particles (VPs). The maximum tolerated
      dose of H103 was not defined. Two patients developed dose-limiting toxicities of
      grade III fever at the dose of 1.5 x 10(12) VP and transient grade IV
      thrombocytopenia at the dose of 3.0 x 10(12) VP. The common adverse events were
      mainly mild to moderate (grade I/II) in nature, including fever, mild injection
      site reaction, leucopenia, lymphopenia, thrombocytopenia and hypochromia. The
      objective response (complete response+partial response) to H103-injected tumors
      was 11.1% (3/27), and the clinical benefit rate (complete response+partial
      response+minor response+stable disease) was 48.1%. Interestingly, transient and
      partial regression of distant, uninjected tumors was observed in three patients.
      The numbers of immune cells (CD4(+) and CD8(+) T cells, and natural killer cells)
      were elevated after H103 administration, but without statistical significance.
      This phase I trial demonstrates that intratumoral administration of H103 can be
      safely applied to cancer patients and shows promising clinical antitumor
      activity, warranting a further clinical investigation.

PMID- 19092860
TI  - Human adipose tissue-derived mesenchymal stromal cells as vehicles for tumor
      bystander effect: a model based on bioluminescence imaging.
AB  - Human adipose tissue mesenchymal stromal cells (AMSCs) share common traits,
      including similar differentiation potential and cell surface markers, with their
      bone marrow counterparts. Owing to their general availability, higher abundance
      and ease of isolation AMSCs may be convenient autologous delivery vehicles for
      localized tumor therapy. We demonstrate a model for tumor therapy development
      based on the use of AMSCs expressing renilla luciferase and thymidine kinase, as
      cellular vehicles for ganciclovir-mediated bystander killing of firefly
      luciferase expressing tumors, and noninvasive bioluminescence imaging to
      continuously monitor both, tumor cells and AMSCs. We show that the therapy
      delivering AMSCs survive long time within tumors, optimize the ratio of AMSCs to
      tumor cells for therapy, and asses the therapeutic effect in real time. Treatment
      of mice bearing prostate tumors plus therapeutic AMSCs with the prodrug
      ganciclovir induced bystander killing effect, reducing the number of tumor cells
      to 1.5 % that of control tumors. Thus, AMSCs could be useful vehicles to deliver
      localized therapy, with potential for clinical application in inoperable tumors
      and surgical borders after tumor resection. This approach, useful to evaluate
      efficiency of therapeutic models, should facilitate the selection of cell types,
      dosages, therapeutic agents and treatment protocols for cell-based therapies of
      specific tumors.

PMID- 19092861
TI  - An oligarchic microbial assemblage in the anoxic bottom waters of a volcanic
      subglacial lake.
AB  - In 2006, we sampled the anoxic bottom waters of a volcanic lake beneath the
      Vatnajokull ice cap (Iceland). The sample contained 5 x 10(5) cells per ml, and
      whole-cell fluorescent in situ hybridization (FISH) and PCR with domain-specific
      probes showed these to be essentially all bacteria, with no detectable archaea.
      Pyrosequencing of the V6 hypervariable region of the 16S ribosomal RNA gene,
      Sanger sequencing of a clone library and FISH-based enumeration of four major
      phylotypes revealed that the assemblage was dominated by a few groups of putative
      chemotrophic bacteria whose closest cultivated relatives use sulfide, sulfur or
      hydrogen as electron donors, and oxygen, sulfate or CO(2) as electron acceptors.
      Hundreds of other phylotypes are present at lower abundance in our V6 tag
      libraries and a rarefaction analysis indicates that sampling did not reach
      saturation, but FISH data limit the remaining biome to <10-20% of all cells. The
      composition of this oligarchy can be understood in the context of the chemical
      disequilibrium created by the mixing of sulfidic lake water and oxygenated
      glacial meltwater.

PMID- 19092862
TI  - Stable isotope probing reveals Trichosporon yeast to be active in situ in soil
      phenol metabolism.
AB  - The aim of this study was to extend the results of our previous stable isotope
      probing (SIP) investigation: we identified a soil fungus involved in phenol
      biodegradation at an agricultural field site. DNA extracts from our previous
      study were examined using fungi-specific PCR amplification of the 18S-28S
      internal transcribed spacer (ITS) region. We prepared an 80-member clone library
      using PCR-amplified, (13)C-labeled DNA derived from field soil that received 12
      daily doses of (13)C-phenol. Restriction-fragment-length-polymorphism screening
      and DNA sequencing revealed a dominant clone (41% of the clone library), the ITS
      sequence of which corresponded to that of the fungal genus Trichosporon. We
      successfully grew and isolated a white, filamentous fungus from site soil samples
      after plating soil dilutions on mineral salts agar containing 250 p.p.m. phenol.
      Restreaking on both yeast extract-peptone-galactose and Sabouraud dextrose agar
      plates led to further purification of the fungus, the morphological
      characteristics of which matched those of the genus Trichosporon. The ITS
      sequence of our isolated fungus was identical to that of a clone from our SIP
      based library, confirming it to be Trichosporon multisporum. High-performance
      liquid chromatography and turbidometeric analyses showed that the culture was
      able to metabolize and grow on 200 p.p.m. phenol in an aqueous mineral salts
      medium within 24 h at room temperature. Gas chromatography-mass spectrometry
      analysis of (13)CO(2) respiration from laboratory soil incubations demonstrated
      accelerated phenol mineralization in treatments inoculated with T. multisporum.
      These findings show that T. multisporum actively degraded phenol in our field
      based, soil experiments.

PMID- 19092864
TI  - Determining the specific microbial populations and their spatial distribution
      within the stromatolite ecosystem of Shark Bay.
AB  - The stromatolites at Shark Bay, Western Australia, are analogues of some of the
      oldest evidence of life on Earth. The aim of this study was to identify and
      spatially characterize the specific microbial communities associated with Shark
      Bay intertidal columnar stromatolites. Conventional culturing methods and
      construction of 16S rDNA clone libraries from community genomic DNA with both
      universal and specific PCR primers were employed. The estimated coverage,
      richness and diversity of stromatolite microbial populations were compared with
      earlier studies on these ecosystems. The estimated coverage for all clone
      libraries indicated that population coverage was comprehensive. Phylogenetic
      analyses of stromatolite and surrounding seawater sequences were performed in ARB
      with the Greengenes database of full-length non-chimaeric 16S rRNA genes. The
      communities identified exhibited extensive diversity. The most abundant sequences
      from the stromatolites were alpha- and gamma-proteobacteria (58%), whereas the
      cyanobacterial community was characterized by sequences related to the genera
      Euhalothece, Gloeocapsa, Gloeothece, Chroococcidiopsis, Dermocarpella,
      Acaryochloris, Geitlerinema and Schizothrix. All clones from the archaeal
      specific clone libraries were related to the halophilic archaea; however, no
      archaeal sequence was identified from the surrounding seawater. Fluorescence in
      situ hybridization also revealed stromatolite surfaces to be dominated by
      unicellular cyanobacteria, in contrast to the sub-surface archaea and sulphate
      reducing bacteria. This study is the first to compare the microbial composition
      of morphologically similar stromatolites over time and examine the spatial
      distribution of specific microorganismic groups in these intertidal structures
      and the surrounding seawater at Shark Bay. The results provide a platform for
      identifying the key microbial physiology groups and their potential roles in
      modern stromatolite morphogenesis and ecology.

PMID- 19092865
TI  - Thermodynamic targeting of microbial perchlorate reduction by selective electron
      donors.
AB  - Here we describe 2,6-anthrahydroquinone disulfonate (AH(2)DS) as a model
      thermodynamically 'targeting' electron donor capable of selectively stimulating
      respiratory processes relevant to the bioremediation of perchlorate. Pure
      cultures of Dechloromonas aromatica, Dechloromonas agitata and Azospira suillum,
      as well as uncharacterized microbial consortia, were capable of
      stoichiometrically reducing perchlorate to chloride upon oxidation of AH(2)DS to
      the corresponding quinone 2,6-anthraquinone disulfonate (AQDS). No degradation of
      the anthraquinone structure was observed, and no organism tested grew by this
      metabolism. Thermodynamic calculations suggest that AH(2)DS oxidation should
      support nitrate and perchlorate reduction, whereas sulfate reduction and
      methanogenesis are predicted to be unfavorable. Mixed community microcosms
      oxidizing AH(2)DS reduced nitrate and perchlorate, whereas sulfate reduction
      never occurred. In contrast, microcosms amended with acetate respired nitrate,
      perchlorate and sulfate, as would be predicted by thermodynamic calculation. Our
      results suggest that the thermodynamic properties of hydroquinones allow for
      targeted stimulation of only a subset of potential respiratory processes. This
      observation could help improve enhanced in situ bioremediation of perchlorate by
      negating many of the detrimental aspects of biofouling.

PMID- 19092866
TI  - Snowball prevention questioned.
AB  - The 'snowball Earth' hypothesis interprets geological evidence as indicating
      multi-million-year episodes of global glaciation near the beginning and end of
      the Proterozoic eon. On the basis of a coupled carbon cycle-climate model,
      Peltier et al. propose that temperature-dependent remineralization of organic
      carbon in a Neoproterozoic ocean with 100-1,000x more dissolved organic carbon
      than today could create a negative climate feedback, thereby preventing a
      snowball Earth. Their results are sensitive to initial conditions and model
      parameters; moreover, important geological observations and components of the
      carbon cycle are not considered-notably the absence of sources or sinks of
      carbon. Their model results fall short of explaining the geological evidence in
      the absence of global glaciation.

PMID- 19092867
TI  - Carbon cycling and snowball Earth.
AB  - The possibility that Earth witnessed episodes of global glaciation during the
      latest Precambrian challenges our understanding of the physical processes
      controlling the Earth's climate. Peltier et al. suggest that a 'hard snowball
      Earth' state may have been prevented owing to the release of CO(2) from the
      oxidation of dissolved organic carbon (DOC) in the ocean as the temperature
      decreased. Here we show that the model of Peltier et al. is not self-consistent
      as it implies large fluctuations of the ocean alkalinity content without
      providing any processes to account for it. Our findings suggest that the hard
      snowball Earth hypothesis is still valid.

PMID- 19092872
TI  - Facilitating the future.

PMID- 19092863
TI  - Spatiotemporal changes in the genetic diversity of a bloom-forming Microcystis
      aeruginosa (cyanobacteria) population.
AB  - The variations in microcystin concentrations during cyanobacterial blooms in
      freshwater ecosystems appear to depend on numerous factors, which have still not
      been fully identified. To contribute to clarify the situation, we have developed
      a spatial sampling approach to determine the dynamics and genetic diversity of a
      bloom-forming population of Microcystis aeruginosa in a large French reservoir,
      and the variations in the proportions of microcystin-producing genotypes. We
      demonstrated that marked changes occurred in the internal transcribed spacer
      (ITS) genotype composition of the M. aeruginosa population during the development
      of the bloom. These changes led progressively to the selection of one dominant
      ITS genotype throughout the entire reservoir when the cell number reached its
      maximum. At the same time, we identified a decrease in the proportion of the
      mcyB+ genotype, and a significant negative correlation between this proportion
      and that of the dominant ITS genotype during the bloom. Thus, it appeared that
      favorable conditions for Microcystis cell growth led to the selection, within the
      Microcystis population, of a non-microcystin-producing genotype, whereas
      potentially microcystin-producing genotypes were dominant in this population
      before and after the bloom, when environmental conditions were less favorable for
      growth.

PMID- 19092874
TI  - Eyes west.

PMID- 19092873
TI  - Machine-makers matter.

PMID- 19092899
TI  - Salary for CIRM head despite deficit.

PMID- 19092906
TI  - Finding of unusual soil on Mars could stem from tools used.

PMID- 19092907
TI  - Online archives are revealing uncensored history of science.

PMID- 19092908
TI  - You're the best man for this job, son. What a coincidence!

PMID- 19092910
TI  - Three rules for technological fixes.

PMID- 19092915
TI  - Migration: an engine for social change.

PMID- 19092916
TI  - Molecular biology: spliceosome meets telomerase.

PMID- 19092917
TI  - Quantum physics: don't look now.

PMID- 19092918
TI  - Circadian clocks: tips from the tip of the iceberg.

PMID- 19092919
TI  - Organometallic chemistry: catalyst takes control to heart.

PMID- 19092920
TI  - Epigenetics: how to lose a tail.

PMID- 19092921
TI  - Condensed-matter physics: the eternal triangle.

PMID- 19092922
TI  - Neuroscience: greasy proteins of the neuron.

PMID- 19092923
TI  - Biogeochemistry: nitrous oxide in flux.

PMID- 19092925
TI  - Sensing voltage across lipid membranes.
AB  - The detection of electrical potentials across lipid bilayers by specialized
      membrane proteins is required for many fundamental cellular processes such as the
      generation and propagation of nerve impulses. These membrane proteins possess
      modular voltage-sensing domains, a notable example being the S1-S4 domains of
      voltage-activated ion channels. Ground-breaking structural studies on these
      domains explain how voltage sensors are designed and reveal important
      interactions with the surrounding lipid membrane. Although further structures are
      needed to understand the conformational changes that occur during voltage
      sensing, the available data help to frame several key concepts that are
      fundamental to the mechanism of voltage sensing.

PMID- 19092926
TI  - Geometric frustration in buckled colloidal monolayers.
AB  - Geometric frustration arises when lattice structure prevents simultaneous
      minimization of local interaction energies. It leads to highly degenerate ground
      states and, subsequently, to complex phases of matter, such as water ice, spin
      ice, and frustrated magnetic materials. Here we report a simple geometrically
      frustrated system composed of closely packed colloidal spheres confined between
      parallel walls. Diameter-tunable microgel spheres are self-assembled into a
      buckled triangular lattice with either up or down displacements, analogous to an
      antiferromagnetic Ising model on a triangular lattice. Experiment and theory
      reveal single-particle dynamics governed by in-plane lattice distortions that
      partially relieve frustration and produce ground states with zigzagging stripes
      and subextensive entropy, rather than the more random configurations and
      extensive entropy of the antiferromagnetic Ising model. This tunable soft-matter
      system provides a means to directly visualize the dynamics of frustration,
      thermal excitations and defects.

PMID- 19092927
TI  - Neural palmitoyl-proteomics reveals dynamic synaptic palmitoylation.
AB  - Palmitoylation regulates diverse aspects of neuronal protein trafficking and
      function. Here a global characterization of rat neural palmitoyl-proteomes
      identifies most of the known neural palmitoyl proteins-68 in total, plus more
      than 200 new palmitoyl-protein candidates, with further testing confirming
      palmitoylation for 21 of these candidates. The new palmitoyl proteins include
      neurotransmitter receptors, transporters, adhesion molecules, scaffolding
      proteins, as well as SNAREs and other vesicular trafficking proteins. Of
      particular interest is the finding of palmitoylation for a brain-specific Cdc42
      splice variant. The palmitoylated Cdc42 isoform (Cdc42-palm) differs from the
      canonical, prenylated form (Cdc42-prenyl), both with regard to localization and
      function: Cdc42-palm concentrates in dendritic spines and has a special role in
      inducing these post-synaptic structures. Furthermore, assessing palmitoylation
      dynamics in drug-induced activity models identifies rapidly induced changes for
      Cdc42 as well as for other synaptic palmitoyl proteins, suggesting that
      palmitoylation may participate broadly in the activity-driven changes that shape
      synapse morphology and function.

PMID- 19092928
TI  - SUMOylation regulates Rad18-mediated template switch.
AB  - Replication by template switch is thought to mediate DNA damage-bypass and
      fillings of gaps. Gap-filling repair requires homologous recombination as well as
      Rad18- and Rad5-mediated proliferating cell nuclear antigen (PCNA)
      polyubiquitylation. However, it is unclear whether these processes are
      coordinated, and the physical evidence for Rad18-Rad5-dependent template switch
      at replication forks is still elusive. Here we show, using genetic and physical
      approaches, that in budding yeast (Saccharomyces cerevisiae) Rad18 is required
      for the formation of X-shaped sister chromatid junctions (SCJs) at damaged
      replication forks through a process involving PCNA polyubiquitylation and the
      ubiquitin-conjugating enzymes Mms2 and Ubc13. The Rad18-Mms2-mediated damage
      bypass through SCJs requires the small ubiquitin-like modifier (SUMO)-conjugating
      enzyme Ubc9 and SUMOylated PCNA, and is coordinated with Rad51-dependent
      recombination events. We propose that the Rad18-Rad5-Mms2-dependent SCJs
      represent template switch events. Altogether, our results unmask a role for PCNA
      ubiquitylation and SUMOylation pathways in promoting transient damage-induced
      replication-coupled recombination events involving sister chromatids at
      replication forks.

PMID- 19092930
TI  - A gravitationally lensed water maser in the early Universe.
AB  - Water masers are found in dense molecular clouds closely associated with
      supermassive black holes at the centres of active galaxies. On the basis of the
      understanding of the local water-maser luminosity function, it was expected that
      masers at intermediate and high redshifts would be extremely rare. However,
      galaxies at redshifts z > 2 might be quite different from those found locally,
      not least because of more frequent mergers and interaction events. Here we use
      gravitational lensing to search for masers at higher redshifts than would
      otherwise be possible, and find a water maser at redshift 2.64 in the dust- and
      gas-rich, gravitationally lensed type-1 quasar MG J0414+0534 (refs 6-13). The
      isotropic luminosity is 10,000 (, solar luminosity), which is twice that of the
      most powerful local water maser and half that of the most distant maser
      previously known. Using the locally determined luminosity function, the
      probability of finding a maser this luminous associated with any single active
      galaxy is 10(-6). The fact that we see such a maser in the first galaxy we
      observe must mean that the volume densities and luminosities of masers are higher
      at redshift 2.64.

PMID- 19092929
TI  - Structure of an argonaute silencing complex with a seed-containing guide DNA and
      target RNA duplex.
AB  - Here we report on a 3.0 A crystal structure of a ternary complex of wild-type
      Thermus thermophilus argonaute bound to a 5'-phosphorylated 21-nucleotide guide
      DNA and a 20-nucleotide target RNA containing cleavage-preventing mismatches at
      the 10-11 step. The seed segment (positions 2 to 8) adopts an A-helical-like
      Watson-Crick paired duplex, with both ends of the guide strand anchored in the
      complex. An arginine, inserted between guide-strand bases 10 and 11 in the binary
      complex, locking it in an inactive conformation, is released on ternary complex
      formation. The nucleic-acid-binding channel between the PAZ- and PIWI-containing
      lobes of argonaute widens on formation of a more open ternary complex. The
      relationship of structure to function was established by determining cleavage
      activity of ternary complexes containing position-dependent base mismatch, bulge
      and 2'-O-methyl modifications. Consistent with the geometry of the ternary
      complex, bulges residing in the seed segments of the target, but not the guide
      strand, were better accommodated and their complexes were catalytically active.

PMID- 19092931
TI  - Unconventional superconductivity in Ba(0.6)K(0.4)Fe2As2 from inelastic neutron
      scattering.
AB  - A new family of superconductors containing layers of iron arsenide has attracted
      considerable interest because of their high transition temperatures (T(c)), some
      of which are >50 K, and because of similarities with the high-T(c) copper oxide
      superconductors. In both the iron arsenides and the copper oxides,
      superconductivity arises when an antiferromagnetically ordered phase has been
      suppressed by chemical doping. A universal feature of the copper oxide
      superconductors is the existence of a resonant magnetic excitation, localized in
      both energy and wavevector, within the superconducting phase. This resonance,
      which has also been observed in several heavy-fermion superconductors, is
      predicted to occur when the sign of the superconducting energy gap takes opposite
      values on different parts of the Fermi surface, an unusual gap symmetry which
      implies that the electron pairing interaction is repulsive at short range. Angle
      resolved photoelectron spectroscopy shows no evidence of gap anisotropy in the
      iron arsenides, but such measurements are insensitive to the phase of the gap on
      separate parts of the Fermi surface. Here we report inelastic neutron scattering
      observations of a magnetic resonance below T(c) in Ba(0.6)K(0.4)Fe(2)As(2), a
      phase-sensitive measurement demonstrating that the superconducting energy gap has
      unconventional symmetry in the iron arsenide superconductors.

PMID- 19092932
TI  - How supercontinents and superoceans affect seafloor roughness.
AB  - Seafloor roughness varies considerably across the world's ocean basins and is
      fundamental to controlling the circulation and mixing of heat in the ocean and
      dissipating eddy kinetic energy. Models derived from analyses of active mid-ocean
      ridges suggest that ocean floor roughness depends on seafloor spreading rates,
      with rougher basement forming below a half-spreading rate threshold of 30-35 mm
      yr(-1) (refs 4, 5), as well as on the local interaction of mid-ocean ridges with
      mantle plumes or cold-spots. Here we present a global analysis of marine gravity
      derived roughness, sediment thickness, seafloor isochrons and palaeo-spreading
      rates of Cretaceous to Cenozoic ridge flanks. Our analysis reveals that, after
      eliminating effects related to spreading rate and sediment thickness, residual
      roughness anomalies of 5-20 mGal remain over large swaths of ocean floor. We
      found that the roughness as a function of palaeo-spreading directions and
      isochron orientations indicates that most of the observed excess roughness is not
      related to spreading obliquity, as this effect is restricted to relatively rare
      occurrences of very high obliquity angles (>45 degrees ). Cretaceous Atlantic
      ocean floor, formed over mantle previously overlain by the Pangaea
      supercontinent, displays anomalously low roughness away from mantle plumes and is
      independent of spreading rates. We attribute this observation to a sub-Pangaean
      supercontinental mantle temperature anomaly leading to slightly thicker than
      normal Late Jurassic and Cretaceous Atlantic crust, reduced brittle fracturing
      and smoother basement relief. In contrast, ocean crust formed above Pacific
      superswells, probably reflecting metasomatized lithosphere underlain by mantle at
      only slightly elevated temperatures, is not associated with basement roughness
      anomalies. These results highlight a fundamental difference in the nature of
      large-scale mantle upwellings below supercontinents and superoceans, and their
      impact on oceanic crustal accretion.

PMID- 19092933
TI  - Conformational changes in an ultrafast light-driven enzyme determine catalytic
      activity.
AB  - The role of conformational changes in explaining the huge catalytic power of
      enzymes is currently one of the most challenging questions in biology. Although
      it is now widely regarded that enzymes modulate reaction rates by means of short-
      and long-range protein motions, it is almost impossible to distinguish between
      conformational changes and catalysis. We have solved this problem using the
      chlorophyll biosynthetic enzyme NADPH:protochlorophyllide (Pchlide)
      oxidoreductase, which catalyses a unique light-driven reaction involving hydride
      and proton transfers. Here we report that prior excitation of the enzyme
      substrate complex with a laser pulse induces a more favourable conformation of
      the active site, enabling the coupled hydride and proton transfer reactions to
      occur. This effect, which is triggered during the Pchlide excited-state lifetime
      and persists on a long timescale, switches the enzyme into an active state
      characterized by a high rate and quantum yield of formation of a catalytic
      intermediate. The corresponding spectral changes in the mid-infrared following
      the absorption of one photon reveal significant conformational changes in the
      enzyme, illustrating the importance of flexibility and dynamics in the structure
      of enzymes for their function.

PMID- 19092935
TI  - Impact of an educational initiative on applied knowledge and attitudes of
      physicians who treat sexual dysfunction.
AB  - A randomized, blinded, multicenter, controlled study was undertaken to assess the
      impact of a multiyear continuing medical education (CME) initiative on physician
      knowledge and behavior in the treatment of erectile dysfunction (ED). The
      objective of this study was to assess the efficacy of CME and compare applied
      knowledge and attitude scores of participants in the Consortium for Improvement
      in Erectile Function (CIEF), to non-CIEF participants. Subjects were selected
      randomly and contacted anonymously, by mail, email and fax and requested to
      enroll in this study. A blinded, validated questionnaire and series of
      standardized patient (SP) case studies and attitude questions were given to CIEF
      participants, defined as those who showed an interest in learning more about ED
      and who took at least one CME-certified program on ED from the CIEF website and
      non-CIEF participants, defined as those who showed interest in learning more
      about ED and who took at least one CME-certified program on ED from any
      organization other than CIEF. The primary outcome was a comparison of subjects'
      scores who participated in at least one CIEF program to non-participants in CIEF
      programs. Subjects were also compared based on SP case scores, attitude scores,
      specialty, years in practice, age and gender. Answers were ranked from best to
      worst and assigned a corresponding value of 10...3, 2, 1 and 0 (10 being the
      best), assuming that there may be more than one correct answer to each question
      in clinical practice. SAS version 9.1 analysis of variance model was used by an
      independent consultant. A total of 120 physicians completed the questionnaire: 87
      urologists (UROs) and 33 primary care physicians (PCPs). UROs scored higher on SP
      cases compared with PCPs (P=0.0039); however, as a result of participating in
      CIEF programs, PCPs trended toward more comparable scores to UROs; P=0.23 for SP
      case 2 that was clinically less complex and P=0.19 for SP case 3 that was more
      complex. In the other two cases, the gap was reduced; however, UROs scored better
      than PCPs. PCPs in CIEF (n=23) had significantly higher SP case scores compared
      with non-CIEF PCPs (n=10); 216.6 vs 191.0, respectively (P=0.0437). PCPs in CIEF
      also showed a significantly greater level in mean attitude scores compared with
      UROs, 10.82 vs 8.15, respectively (P<0.0001). Both PCPs and UROs scored higher
      after participating in CIEF ED educational programs than those clinicians who
      participated in non-CIEF ED educational programs. In addition, clinicians
      participating in more CIEF programs scored higher than those participating in
      fewer CIEF programs. As expected, UROs consistently scored better than PCPs,
      indicating a higher baseline level of knowledge base about ED. However, this
      educational gap was significantly reduced in PCPs who participated in CIEF
      programs. The study demonstrated that PCPs who took more CIEF courses were almost
      as knowledgeable as UROs on the subject of ED. Longitudinal, disease-specific CME
      initiatives are valuable in that they positively impact the knowledge and thus
      the behavior of participating physicians, potentially conferring clinical
      benefits toward patient outcomes.

PMID- 19092936
TI  - Role-reversal: a somewhat neglected mirror of heritages of the past.
AB  - Within a clinical-theoretical framework focused on transference
      countertransference dynamics, the authors reflect on role-reversal and on the
      reasons it has been neglected for a long time in literature. This primitive inter
      and intra-psychic process, often at the forefront in our practice, will be
      discussed in its principal aspects (patient's unconscious identification with
      parents' psychic culture and concomitant dissociation of the infant part of the
      self), signaling how the enactment can be an inevitable element which, putting
      into play the past dissociated object relationships, becomes a source of mutative
      understanding.

PMID- 19092937
TI  - Authenticity as an aim of psychoanalysis.
AB  - This paper will present a series of predominantly clinical observations
      concerning the lengthy work a patient carries out, with the help of the analyst,
      in order to achieve greater personal authenticity. When this work is drawing to a
      close and the patient has gained a degree of authenticity, this authenticity
      remains within him, almost without his realizing it. The power of authenticity is
      instead revealed through the patient's most intimate and important relationships.
      In the long term, the patient's authenticity also alters his perception of
      himself and of his role in the world. He feels more alive and less overcome by a
      sense of futility, if earlier this had been the case.

PMID- 19092938
TI  - Reverie and metaphor: a particular way to investigate the unconscious.
AB  - A particular way of using reveries to explore the unconscious (both with patients
      and colleagues in supervision) will be illustrated. For this purpose, I'll use
      reverie not in Bion's sense, but in its meaning of "daydream." It seems quite
      probable that anyone can produce a reverie out of any stimulus, although a
      certain amount of training is usually necessary. I shall describe what I mean
      when I say that one has to be able to let oneself go when using a very old
      technique that helps produce reveries. Once obtained, reveries can be explored
      similarly to the way we use dreams in psychoanalysis. One of the main focuses of
      this paper will be to show how everyday metaphors can be transformed into
      reveries. Several examples will be given. This technical instrument should help
      analysts to achieve two basic objectives: to improve their own capacity, and that
      of the patient, to contain; and to avoid making intrusive interpretations
      (without giving up this basic psychoanalytical tool altogether).

PMID- 19092939
TI  - Alter(ing) potential space: personalization and community in psychoanalytic
      therapy.
AB  - In this paper, I use the notion of alterity to amend Winnicott's view of
      potential space. I suggest that the parent's potential space--omnipotent
      recognition and treatment of the baby as person--makes possible the baby's belief
      in and experience of omnipotence, which is manifested in his/her omnipotent
      recognition and treatment of objects in terms of utility, pleasure, and function.
      This early manifestation of potential space gives way to recognition of objects
      as proto-persons, which accompanies the child's illusion that the (transitional)
      object recognizes him/her as a person. Here the child learns to surrender to the
      object's omnipotent constructions and, in these moments, there is a proto
      communion--an illusory experience of mutual joining together as persons. This
      eventually gives way to a potential space wherein two or more people mutually and
      omnipotently construct and surrender to each other as persons, subordinating
      pleasure, function, and utility to the recognition of the Other as person. This
      depiction of potential space can serve as a framework for understanding the
      process of therapy as a struggle not simply of reality and illusion, but one of
      recognition and treatment of Others as persons and the possibility of communion
      and community.

PMID- 19092940
TI  - Lacan's concept of desire and its vicissitudes.
AB  - This paper counterbalances Lacan's dictum that desire is structured like a
      signifying chain by highlighting his dependence on a biological understanding of
      the sexual drive. Reiterating (and reinterpreting) Freud's "leaning on"-
      hypothesis about the genesis of desire, Lacan maintains that the sexual drive
      originates in the vital function. His ideas about male and female sexuality most
      clearly presuppose a biological understanding of the sexual drive. At various
      times, Lacan blurs the lines of his own conceptual difference between phallus and
      penis, up to the point of reducing the difference between the sexes to an
      opposition.

PMID- 19092944
TI  - [Contemporary medical history--a potential battlefield].

PMID- 19092945
TI  - [Ultrasound--what everybody saw, but nobody heard].

PMID- 19092946
TI  - [Action against tuberculosis--all has its time].

PMID- 19092943
TI  - Dual role of COUP-TF-interacting protein 2 in epidermal homeostasis and
      permeability barrier formation.
AB  - COUP-TF-interacting protein 2 (CTIP2; also known as Bcl11b) is a transcription
      factor that plays key roles in the development of the central nervous and immune
      systems. CTIP2 is also highly expressed in the developing epidermis, and at lower
      levels in the dermis and in adult skin. Analyses of mice harboring a germline
      deletion of CTIP2 revealed that the protein plays critical roles in skin during
      development, particularly in keratinocyte proliferation and late differentiation
      events, as well as in the development of the epidermal permeability barrier. At
      the core of all of these actions is a relatively large network of genes,
      described herein, that is regulated directly or indirectly by CTIP2. The analysis
      of conditionally null mice, in which expression of CTIP2 was ablated specifically
      in epidermal keratinocytes, suggests that CTIP2 functions in both cell and non
      cell autonomous contexts to exert regulatory influence over multiple phases of
      skin development, including barrier establishment. Considered together, our
      results suggest that CTIP2 functions as a top-level regulator of skin
      morphogenesis.

PMID- 19092947
TI  - [Who will die in peace?].

PMID- 19092948
TI  - [Before and after implementation of do-not-resuscitate orders in a stroke unit].
AB  - BACKGROUND: In Norway, few studies have been done to map the extent of do-not
      resuscitate (DNR) orders and the consequence for patients (treatment and
      outcome). MATERIAL AND METHODS: All patients with DNR orders, referred to the
      stroke unit of Akershus University Hospital during the year 2005, were identified
      and data on treatment and outcome were recorded. RESULTS: A DNR order was found
      for 79 of 855 (9 %) patients (mean age 80 years [SD 9]). Reasons for referral to
      hospital were: cerebral infarction (49 [62 %] patients), intracerebral
      haemorrhage (28 [35 %] patients), and other diseases (2 [3 %] patients). Mean NIH
      Stroke Scale was 19 (SD 6) (scale 0 - 42; 0 in score meaning no stroke related
      symptoms). Hospital mortality was 39/79 (49 %). Apart from once, all decisions
      regarding withholding and/or withdrawing life-sustaining treatment were taken in
      the aftermath of a DNR order. For 43 patients (54 %), treatment was limited in
      some way and hospital mortality for this group was 27/43 (63 %). Mortality was
      12/36 (33 %) for those who had full treatment. 45 patients (57 %) with a DNR
      order had a bacterial infection and 32 of them were treated with antibiotics (71
      %). INTERPRETATION: Patients with DNR orders were old and had had severe stroke.
      Treatment was rarely withheld despite high morbidity and mortality among the
      patients.

PMID- 19092950
TI  - [Brugada syndrome].

PMID- 19092949
TI  - [Health care professionals' handling of patient data].
AB  - BACKGROUND: Health care professionals' handling of patient data is to a large
      extent subject to legislation. The legal obligations are linked to individual
      professional authorization, and obligations imposed on health care institutions.
      The latter type of obligation is particularly relevant to the use of IT systems.
      MATERIAL AND METHODS: An anonymous questionnaire survey was undertaken the autumn
      2007. 300 physicians, 200 medical secretaries and 200 radiographs were asked
      about their personal experience with situations requiring handling of patient
      data subject to legislation. RESULTS: The overall response rate was 54.7
      (395/688). Health care professionals relatively often come into situations in
      which they can, ought to or have to make exceptions from the general secrecy
      obligation. A discretionary decision is often needed when patient data are
      disclosed to a third party or even when patients are granted access to their own
      personal records. In most such situations, health care professionals comply with
      their patients' wishes. Regulations on handling of patient data are usually
      adhered to. The largest category of breaches is by far "snooping" into IT
      systems, because of curiosity or for other reasons, which are neither
      professionally nor ethically reputable. INTERPRETATION: "Traditional"
      obligations, linked to individual professional authorizations, and well-defined
      patient rights are largely respected and met. Internal routines and guidelines,
      in an enterprise subject to system control requirements, are violated more
      frequently.

PMID- 19092951
TI  - [Cytochrome P-450 3A4--the most important arena for drug interactions in the
      body].
AB  - BACKGROUND: Drug metabolism is often dependent on the cytochrome P-450 enzyme
      CYP3A4. Some drugs are powerful inhibitors of CYP3A4, whereas others are
      inducers. Thus, numerous drug interactions are caused by altered CYP3A4 enzyme
      activity. MATERIAL AND METHOD: Based on our own continuous work with drug
      interactions during the last 10 - 15 years, we here present an overview of the
      most important CYP3A4 interactions and suggestions on how to handle them in
      clinical practice. RESULTS: The combination of a drug being a powerful inhibitor
      of CYP3A4 and a drug dependent on CYP3A4 for its metabolism may increase the
      plasma levels of the substrate as much as 10 to 20-fold, with adverse drug
      reactions and toxic effects as a result. Correspondingly, a combination with an
      inducer may cause a decrease in the plasma level of the substrate to only 5 - 10
      % of its original concentration, leading to therapeutic failure. INTERPRETATION:
      One should avoid drug combinations that cause such profound changes in substrate
      plasma levels as those described above. With smaller changes in plasma levels an
      alternative is to combine dose adjustments with frequent clinical controls.

PMID- 19092952
TI  - [Good communication--also for the physicians' sake!].

PMID- 19092953
TI  - [The view of elderly physicians on the loss of licensure at the age of 75].

PMID- 19092954
TI  - [Should pregnant women be screened for asymptomatic bacteriuria?].

PMID- 19092955
TI  - [Mortality in Norway and USA].

PMID- 19092956
TI  - [Treatment of erythema migrans].

PMID- 19092957
TI  - [Urogenital problems and female Internet users].

PMID- 19092958
TI  - [Risk assessment in home childbirth].

PMID- 19092960
TI  - [The lawyers' crusade against an invented reality].

PMID- 19092961
TI  - [The sugar is more dangerous than the car].

PMID- 19092962
TI  - [Uncertain about climate changes].

PMID- 19092964
TI  - [Why do Ibsen's children die?].
AB  - Death of children is a remarkably frequent theme in Henrik Ibsen's writings and
      may be a key to understanding of his work. In this paper I refer to writings
      where children die, and I analyze case histories and question of causes. The
      medical courses are very diverse. In his earliest works, some children die by
      starvation. In our time we tend to forget the enormous child mortality rate in
      Norway during the mid 1800s. In his contemporary dramas, the causes of death are
      often complex. Even though he uses symbols, there are elements that are medically
      reasonable. He rarely makes mistakes in a medical context. A common feature in
      these tragic child destinies is that the poet shows us inadequate and poor
      parents.

PMID- 19092965
TI  - [From politics to ethics--obstetric ultrasound in 1980's and 1990's].

PMID- 19092966
TI  - [Care for the mentally ill in the Norwegian counties Troms and Finnmark 1891
      1940].
AB  - The article discusses care for the mentally ill, as it emerged and developed in
      Troms and Finnmark counties in 1891 - 1940. The main objective was to document
      how publicly supported private care functioned with respect to the well-being of
      the mentally ill and their situation. How mental illness was defined and
      perceived by close relatives, care providers, medical practitioners and public
      authorities was also assessed. Medical records written by district physicians
      have been central sources; other sources were records from the county council
      proceedings and public statistics on poverty and health. The private care
      arrangement was the dominant type of care for the mentally ill in the region
      throughout the period. This arrangement was subject to public supervision, but
      its functioning depended on periodic support from somatic institutions and even
      prisons. The study shows that private care was a well-functioning arrangement in
      many cases. The mentally ill were often included in the household work and daily
      life practices on the farm. The private care system however displayed wide
      variations, as its quality depended on the care providers, district physicians
      and last but not least economic support from the local community.

PMID- 19092967
TI  - [Tuberculosis prevention in Finnmark 1900-1960].
AB  - The campaign against tuberculosis in Finnmark in the first half of the 20th
      century was defined as a national responsibility. The Norwegian state and
      voluntary associations, the Norwegian Association against Tuberculosis prominent
      among them, initiated special measures against the disease in this multicultural
      county. It was considered important to increase the capacity for isolation of
      patients, but efforts to enhance the populations' cultural and social standards,
      particularly among the Sami, were also prioritized. In the decades between wars,
      a stronger emphasis was placed on strict epidemiological measures. However,
      cultural concerns surfaced anew in a new medical and political context in the
      preventive work from 1952, in connection with implementation of mass miniature X
      ray screenings in Finnmark.

PMID- 19092968
TI  - [Tuberculosis in the Royal Norwegian Navy at the time of the Second World War].
AB  - Tuberculosis became a great problem in the Royal Norwegian Navy during the first
      years of the Second World War (when it operated in allied services mainly from
      the UK); with the highest incidence (9.6 per 1 000) during the first half of
      1943. Main reasons were insufficient medical examination of recruits, crowded
      living conditions on board (favoured the contagion) and the physical and
      psychological pressure during sea operations, which may have reduced the immune
      defence. Prophylactic measures in terms of tuberculin testing of all personnel,
      chest X-rays of the positives, vaccination of the negatives, environment
      investigation when disease was discovered, and isolation of those infected, gave
      control from the second half of 1943 and onwards. The article also mentions
      treatment, repatriation and the incidence of tuberculosis in the Norwegian Navy
      before and after the war as well as in the Royal Canadian Naval Services (where
      the incidence was low) during the war. Today, the tuberculosis situation in
      Norway is so favourable that routine chest X-ray of the recruits is no longer
      performed in the armed forces.

PMID- 19092969
TI  - [Abreugraphy and the introduction of mass X-ray screening to Norway].
AB  - The Brazilian radiologist Manoel de Abreu (1892 - 1962) was the first who
      succeeded in developing an apparatus suitable for mass radiography of the chest
      in the fight against tuberculosis. Within a few years, many countries had started
      to use mass radiography. The German professor Hans Holfelder (1891 - 1944)
      improved the apparatus and made a transportable version to be used in special
      buses and in assembly halls. When Germany attacked Norway in April 1940, the
      Chief Tuberculosis Inspector Otto Galtung (1904 - 81), was making plans for a
      nation-wide screening programme with mass radiography. He was fired by the Nazis
      who continued his work and started screening in 1943. The first mass radiography
      in Norway was carried out in Bergen in September 1940. Almost 11 000 pupils and
      teachers from all schools in Bergen were examined under the management of
      Holfelder, then an SS-Standartenfuhrer (colonel) and radiologist in the
      occupation force. The screening was performed in co-operation with the municipal
      health authority who bought the apparatus in spring 1941.

PMID- 19092970
TI  - [Did Henrik Wergeland have AD/HD?].
AB  - Henrik Wergeland (1808 - 45) is one of Norwegian cultural history's most notable
      figures. He is honoured as a national symbol during this year's 200-year jubilee
      for his birth. Biographies and numerous academic publications have been written
      about him for more than 100 years. His life was short and diverse; on one hand he
      continuously worked to give people general education, he was an author and a poet
      and on the other hand he was always in a dispute with someone and involved in
      endless court cases and scandals. After his death it was said that Wergeland was
      one who <<had to loose because of his thoughtlessness, recklessness and lack of
      worldly wisdom>>. As I see it, his life is so full of events that indicate
      hyperactivity and impulsivity that I think it is legitimate to ask whether he
      would have received the diagnosis AD/HD (attention-deficit/ hyperactivity
      disorder) today.

PMID- 19092971
TI  - [Father of the journalalogy].

PMID- 19092972
TI  - [Psychiatry in poor countries: no health without mental health!].

PMID- 19092976
TI  - Boosted protease inhibitor-based or nonnucleoside reverse transcriptase-based
      HAART: is there a best choice for antiretroviral-naive HIV-1 infected patients?
AB  - Since 1996 and the introduction of highly active antiretroviral therapies,
      multiple drugs have been developed. The best choice of drugs to start with still
      remains debated, especially regarding the choice between protease inhibitor-based
      or nonnucleoside reverse transcriptase inhibitor-based regimens. Regarding the
      regimen's ability to control viral replication, both have been proven to be very
      efficient in large settings of patients. Regarding short-term tolerability, both
      classes are responsible for various side effects in 10-25% of patients. Regarding
      long-term tolerability, protease inhibitor-based regimens may be responsible for
      metabolism abnormalities (hypertriglyceridemia, diabetes), although the role of
      the associated nucleoside reverse transcriptase inhibitor is not always clear.
      Patient adherence to the regimen is the cornerstone of efficacy. Resistance
      acquisition in case of poor adherence leading to treatment failure is a key issue
      regarding the ability to build future efficient regimens. Failure while using
      protease inhibitor-based regimens seldom leads to acquired resistance. Failure
      while using nonnucleoside reverse transcriptase inhibitor-based regimens leads to
      resistance, but the new available nonnucleoside reverse transcriptase inhibitors
      do not share the same patterns of resistance, so that the well-known "class
      resistance" in case of nonnucleoside reverse transcriptase inhibitor failure is
      no longer valid. Drug-drug interactions are frequent with all antiretrovirals and
      require close monitoring. In conclusion, protease inhibitor-based and
      nonnucleoside reverse transcriptase inhibitor-based regimens each have many
      advantages. The best choice will essentially be made taking into account the
      patients' characteristics.

PMID- 19092975
TI  - HTLV-1 Yin and Yang: Rex and p30 master regulators of viral mRNA trafficking.
AB  - Human retroviruses are associated with a variety of malignancies including
      Kaposi's sarcoma and Epstein-Barr virus-associated lymphoma in HIV infection, T
      cell leukemia/lymphoma and a neurologic disorder in human T-cell lymphotropic
      virus type 1 (HTLV-1) infection. Both HIV and human T-cell lymphotropic virus
      type 1 have evolved a complex genetic organization for optimal use of their
      limited genome and production of all necessary structural and regulatory
      proteins. Use of alternative splicing is essential for balanced expression of
      multiple viral regulators from one genomic polycistronic RNA. In addition,
      nuclear export of incompletely spliced RNA is required for production of
      structural and enzymatic proteins and virus particles. Decisions controlling
      these events are largely guarded by viral proteins. In human T-cell lymphotropic
      virus type 1, Rex and p30 are both nuclear/nucleolar RNA binding regulatory
      proteins. Rex interacts with a Rex-responsive element to stimulate nuclear export
      of incompletely spliced RNA and increase production of virus particles. In
      contrast, human T-cell lymphotropic virus type 1 p30 is involved in the nuclear
      retention of the tax/rex mRNA leading to inhibition of virus expression and
      establishment of viral latency. How these two proteins, with apparently opposite
      functions, orchestrate virus replication and ensure vigilant control of viral
      gene expression is discussed.

PMID- 19092977
TI  - Role of genetic diversity amongst HIV-1 non-B subtypes in drug resistance: a
      systematic review of virologic and biochemical evidence.
AB  - The genetic diversity of HIV-1 has required its classification into types and
      subtypes. There is controversy as to how and to what extent genetic diversity may
      affect the emergence of antiretroviral drug resistance in HIV-1 subtypes other
      than B. To better understand the impact of genetic diversity (represented by
      different HIV-1 subtypes) on resistance to reverse transcriptase and protease
      inhibitor drugs, a systematic review was conducted on virologic and biochemical
      evidence obtained from work with non-B HIV-1 subtypes. We searched 11 databases
      and retrieved 3,486 citations on all aspects of non-B subtype-related resistance
      research. Twenty-seven studies with virologic and/or biochemical data met the
      eligibility criteria for our systematic review. Nineteen studies were found that
      reported phenotypes in non-B subtypes (304 from naive isolates and 242 from drug
      exposed isolates) and 11 studies that used molecular biology techniques to study
      non-B resistance to antiretroviral drugs. Compared to the NL4-3 laboratory
      strain, lower baseline susceptibilities of recombinant A/G subtype virus to
      protease inhibitors were observed and a substantial proportion of subtype C
      isolates displayed higher IC50 at baseline for atazanavir. Some A/G isolates were
      found to have reduced susceptibility to abacavir. Mutations not typical of B
      subtypes include the reverse transcriptase mutation V106M and the protease
      mutations M89I/V and N83T. Virologic and biochemical data suggest that K65R is
      more likely to emerge in subtype C HIV-1. There is evidence to suggest
      differential effects of other mutations according to subtype, e.g. the protease
      inhibitor mutations I93L and M89I/V. Importantly, the most widely used commercial
      phenotyping systems do not take into account gag variations among natural
      isolates, which could limit the accuracy of measured susceptibility. Enzymatic
      and virologic data support the concept that naturally occurring polymorphisms in
      different non-B subtypes can affect the susceptibility of HIV-1 to different
      antiretroviral drugs, the magnitude of resistance conferred by major mutations,
      and the propensity to acquire some resistance mutations. Tools may need to be
      optimized to accurately measure drug susceptibility of non-B subtypes, especially
      for protease inhibitors.

PMID- 19092978
TI  - Effects of mutations in the connection and RNase H domains of HIV-1 reverse
      transcriptase on drug susceptibility.
AB  - Despite the success in the development of antiretroviral therapy, the emergence
      of drug resistance remains an important factor that can undermine the benefits of
      treatment. The vast majority of well-described resistance-associated mutations
      are clustered around the binding site for a given inhibitor. However, mutations
      that are observed at considerable distance from this location can likewise affect
      drug susceptibility. Treatment-associated mutations in the C-terminal region of
      HIV-1 reverse transcriptase provide a recently surfaced example in this regard.
      In this review, we discuss the potential clinical significance of these mutations
      and underlying molecular mechanisms. Routine resistance testing does not usually
      include the C-terminal region of HIV-1 reverse transcriptase. However, previous
      studies have shown that mutations in this region can reduce susceptibility to
      both nucleoside and nonnucleoside reverse transcriptase inhibitors. The
      prevalence of some of these mutations can be as high as reported for several
      classic resistance mutations in HIV-1 reverse transcriptase. Biochemical studies
      provided plausible mechanisms that help to explain how certain C-terminal
      mutations can contribute to alterations in drug susceptibility and viral
      replication capacity. Overall, the available data warrant further investigation
      on the impact of C-terminal mutations in combination with classic resistance
      associated mutations, on changes in viral load, and response to treatment with
      different classes of reverse transcriptase inhibitors.

PMID- 19092979
TI  - CD4+ guided antiretroviral treatment interruption in HIV infection: a meta
      analysis.
AB  - The aim of this meta-analysis study was to evaluate the relative risk of death or
      AIDS-defining events associated to CD4+ guided treatment interruption in patients
      with chronic HIV infection. A search was conducted using PubMed and Cochrane
      Library; key words for PubMed were: "antiretroviral therapy and interrupt*" in
      the full papers from January 1, 2000 up to and including December 31, 2007. To
      limit the publication bias, clinical trials performed on the topic of the meta
      analysis were searched also on http://www.clinicaltrial.gov. Inclusion criteria
      of studies were: starting a CD4+ guided interruption of HAART in HIV chronically
      infected patients with CD4+ cell count > 350 cells/mm3, age > 13 years old, and
      absence of concomitant use of immunomodulatory drugs. Using a conservative
      approach, to be included in the meta-analysis, studies had to have a follow up
      period > 100 person years to minimize the bias of a too short observation time.
      The studies were classified into two categories: randomized clinical trial (one
      arm stops therapy and other arms continues HAART) and cohort studies. For each
      study measures of effect (hazard ratio or incidence rate ratio) were reported,
      when available, uncorrected and corrected for potential confounders. Publication
      bias was assessed graphically through funnel plot. Pooled relative risk and
      pooled risk difference were calculated by use of a random effects model following
      the DerSimonian-Laird method. Observational studies were considered separately
      and the incidence of primary endpoint was evaluated in each study and the
      cumulative incidence was calculated. Of the 555 full papers found, all abstracts
      were screened and 58 full text articles for potential inclusion were retrieved
      and 18 were retained (seven randomized clinical trials and 11 observational
      studies). In randomized clinical trials, the meta-analysis showed that the pooled
      relative risk of AIDS-defining event or mortality was 2.50 (95% CI: 1.87-3.34; p
      < 0.001); the pooled risk difference of AIDS-defining event or mortality was 0.02
      (95% CI: capital ER, Cyrillic0.01-0.05; p = 0.168). The respective values
      corrected for latest CD4+ value were 1.77 (95% CI: 1.29-2.42; p < 0.001) and 0.01
      (95% CI: capital ER, Cyrillic0.01-0.02; p = 0.37). The pooled relative risk of
      death was 1.8 (95% CI: 1.18-2.77; p = 0.007), and the corresponding pooled risk
      difference was 0.01 (95% CI: 0.001-0.012; p = 0.03). The risk of death resulted
      to have increased in patients that interrupted treatment; the corresponding value
      of risk difference was significant, although it was low (one extra death per 100
      person years). Considering that a separate analysis corrected for the latest CD4+
      value was not feasible for this endpoint, and that mortality rates in HIV
      infected patients are inversely correlated with the CD4+ count, the value
      reported is extremely conservative. In cohort studies, the cumulative incidence
      of deaths or AIDS-defining events in the five studies with follow-up > 100 person
      years, was 0.77 (95% CI: 0.37-1.42 events per 100 person years), ranging in
      different studies from 0 to 3.2 events per 100 person years. This meta-analysis
      suggests that in patients undergoing a treatment interruption, there is an
      increased risk of developing AIDS or death, and that this risk is decreased if a
      relatively high CD4+ threshold is chosen to reinitiate the treatment, while the
      risk difference does not reach statistical significance.

PMID- 19092980
TI  - Acute hepatitis C in HIV-positive individuals.
AB  - Due to the asymptomatic nature of acute hepatitis C it can be difficult to
      diagnose in the early stage of infection, but with the higher treatment success
      rates and reduced treatment duration at this stage, it is imperative that
      diagnoses are made. Therefore, physicians should routinely screen at-risk
      individuals and investigate abnormal liver function tests. Serum HCV RNA should
      be considered in any HCV-antibody-negative individual in whom acute HCV is
      clinically suspected, or annually in those high-risk individuals with previous
      infection. Acute hepatitis C transmission may be facilitated by the presence of
      an erosive genital lesion, such as syphilis or lymphogranuloma venereum, and thus
      testing at this time should be encouraged. Reinfection with HCV does occur and
      patients need to be informed of the sexual and other high-risk behaviors that put
      them at risk of reinfection. Public awareness of the possibility of HCV
      infection, and subsequent reinfection, in high-risk groups should be increased.
      The question of the optimal treatment regimen is still disputed. However, ongoing
      trials and the proposed randomized controlled trial from the European AIDS
      Treatment Network should answer many of our questions. In the meantime, units
      faced with HIV/acute hepatitis C coinfection should follow recommendations from
      the HCV-HIV International Panel.

PMID- 19092983
TI  - Interferons and progesterone for establishment and maintenance of pregnancy:
      interactions among novel cell signaling pathways.
AB  - Type I and/or type II interferons (IFNs) are important in establishing uterine
      receptivity to implantation in mammals. Gene expression effected by IFNs may be
      induced, stimulated or inhibited, but most are IFN-stimulated genes (ISGs).
      Effects of IFNs range from pregnancy recognition signaling in ruminants by IFN
      tau (IFNT) to effects on cellular functions of the uterus and uterine
      vasculature. For most, if not all, actions of IFNs on the uterus, progesterone
      (P(4)) is permissive to ISG expression, with genes being induced by IFN or
      induced by P(4) and stimulated by IFN. Uterine receptivity to implantation is
      P(4)-dependent; however, implantation events are preceded by loss of expression
      of progesterone (PGR) and estrogen (ESR1) receptors by uterine epithelia. Thus,
      P4 likely stimulates PGR-positive stromal cells to express one or more
      progestamedins, e.g., fibroblast growth factors-7 and -10, and/or hepatocyte
      growth factor, that act via their respective receptors on uterine epithelia and
      trophectoderm to regulate expression of ISGs. FGF10 appears to be the most
      important progestamedin in sheep uteri during pregnancy. Sequential effects of
      P(4) to induce and IFNs to stimulate gene expression suggest that P(4) and IFNs
      activate complimentary cell signaling pathways to modulate expression of genes
      for attachment of trophectoderm to uterine lumenal and superficial glandular
      epithelia (LE/sGE), modify phenotype of uterine stromal cells, silence PGR and
      ESR1 genes, signal pregnancy recognition, suppress genes for immune recognition,
      alter membrane permeability to enhance conceptus-maternal exchange of factors,
      increase endometrial vascularity and activate genes for transport of nutrients
      into the uterine lumen. In ewes, IFNT abrogrates the uterine luteolytic mechanism
      and stimulates expression of classical ISGs by GE and stromal cells, whereas
      LE/sGE express P(4)-induced and IFNT-stimulated genes important for uterine
      receptivity to implantation and conceptus development. These include wingless
      type MMTV (mouse mammary tumor virus) integration site family member 7A (WNT7A)
      induced by IFNT, as well as galectin, proteases, protease inhibitors,
      transporters for glucose and amino acids, gastrin releasing polypeptide, insulin
      like growth factor binding protein 1 and a hypoxia inducible factor. The specific
      functions of IFNs and ISGs induced in primates, pigs and other mammals during
      pregnancy are not known, but likely are important in establishment of pregnancy.
      Understanding the roles of IFNs and ISGs in uterine receptivity for implantation
      is necessary to develop strategies to enhance reproductive health and fertility
      in humans and domestic animals. The magnitude of the LH surge was reduced in cows
      receiving endotoxin.

PMID- 19092984
TI  - Endometrial and myometrial secretion of androgens and estrone during early
      pregnancy and luteolysis in pigs.
AB  - Previously, we found that in addition to embryos, the uterine tissues may be a
      source of estradiol-17beta (E(2)) during early pregnancy in the pig. The aim of
      the present study was to determine whether porcine endometrium and myometrium
      secrete androgens - androstenedione (A(4)), testosterone (T) and estrone (E(1))
      during early pregnancy and luteolysis (Days 14-16) in pigs. Individual
      endometrial and myometrial slices (200 mg) were first pre-incubated (24 h) and
      then incubated (6 h, 37 degrees C in an atmosphere of 95% O(2) and 5% CO(2)) in
      the presence or absence of progesterone (P(4); 10(-5) M), oxytocin (OT; 10(-7) M)
      or OT plus P(4). Basal endometrial and myometrial secretion of A(4) and T did not
      differ between pregnant and cyclic gilts. Endometrial secretion of E(1) was
      higher in pregnant than cyclic gilts (p<0.05) while myometrial secretion of E(1)
      did not differ between the two groups of the examined pigs (p>0.05). Progesterone
      significantly increased A(4) and T secretion (p<0.001) by uterine tissues
      regardless of the reproductive status. In the presence of P(4), endometrial and
      myometrial secretion of E(1) was increased only during luteolysis (p<0.001). In
      both tissues, OT did not affect the examined steroid secretion and did not change
      the effect of P(4). IN CONCLUSION: 1) porcine endometrium and myometrium was
      found to produce A(4), T and E(1) in vitro; 2) basal endometrial and myometrial
      production of A(4) and T did not differ between the examined reproductive
      periods; 3) the endometrium released more E(1) during early pregnancy than
      luteolysis; 4) in the presence of substrate (P(4)), uterine tissues increased
      secretion of A(4) and T during early pregnancy and luteolysis; and 5) P(4)
      increased uterine production of E(1) only during luteolysis. These data
      demonstrated the presence of the active steroid pathway in porcine endometrium
      and myometrium which may serve as an alternative source of androgens and
      estrogens in pigs.

PMID- 19092985
TI  - Application of clinical indices of fetal growth and wellbeing to a novel
      laboratory species, the spiny mouse.
AB  - Ultrasound was used to measure growth of the spiny mouse fetus throughout
      gestation and to record Doppler measurements of heart rate and umbilical blood
      flow to monitor fetal blood supply and wellbeing. Female spiny mice were
      anesthetized on 6 occasions throughout pregnancy. Ultrasound was performed with a
      Philips HDI 5000 machine using a compact linear CL15-7 transducer. Fetal heart
      rate and growth parameters increased across gestation. Blood flow through the
      umbilical artery and vein showed increasing velocity over gestation, and reduced
      resistance index. Blood flow through the ductus venosus also increased in
      velocity over gestation; however the resistance index remained constant. We have
      determined changes in umbilical blood flow throughout pregnancy in the spiny
      mouse, which resemble those seen in human pregnancy. We also confirm that
      ultrasound can be used as a valuable, non-invasive technique for measuring fetal
      growth and wellbeing in the spiny mouse.

PMID- 19092986
TI  - The influence of tumor necrosis factor alpha (TNF) on the secretory function of
      bovine corpus luteum: TNF and its receptors expression during the estrous cycle.
AB  - Tumor necrosis factor alpha (TNF) inversely regulates the function of bovine
      corpus luteum (CL). Whereas the low doses of TNF induce luteolysis, the high
      doses prolong CL lifespan and prevent luteolysis in vivo. We suggest that the
      varying effects of TNF may be caused by its action exerted on CL via multiple
      signaling pathways involving two distinct receptors: TNFR-I (responsible for
      induction of the cell death) and TNFR-II (implicated in cell proliferation). In
      the study, we determined CL expressions of TNF, TNFR-I and TNFR-II mRNAs during
      the bovine estrous cycle using semi-quantitative RT-PCR. Specific transcripts for
      TNF, TNFR-I and TNFR-II were found in the CL with the highest (p<0.05) expression
      in the regressed CL. We also examined the TNF influence on the bovine CL function
      in vivo. On Day 15 of the estrous cycle, cows were infused (via aorta
      abdominalis) with saline, TNF (1 or 10 microg) or analogue of prostaglandin
      (PG)F(2alpha) (aPGF(2alpha) , 500 microg; a positive control). Four hours after
      infusions, CLs were collected by colpotomy and luteal contents of progesterone
      (P(4)), stable metabolites of nitric oxide (NO; nitrite/nitrate), leukotriene
      (LT)C(4), luteolytic PGF(2alpha),and luteotropic PGE(2) were determined.
      Moreover, caspase-3 activity was measured in the CLs as an indicator of apoptosis
      induction. The luteal content of P(4) decreased (p<0.05) after infusion of 1
      microg of TNF. TNF inversely affected PGs content in CL: the low dose increased
      (p<0.01) the PGF(2alpha) level and the high dose increased (p<0.05) PGE(2) level.
      Contents of LTC(4) and nitrite/nitrate increased (p<0.01) after the low dose of
      TNF. Moreover, 1 microg of TNF induced apoptosis and increased (p<0.05) caspase-3
      activity in the CLs collected during the late luteal phase. In conclusion, the
      high expressions of TNF and TNF receptors mRNAs were observed during or just
      after the luteolysis. A low concentration of TNF stimulated in vivo luteolytic
      factors such as PGF(2alpha), LTC(4) and NO as well as induced apoptosis; whereas
      the high concentration of TNF stimulated a survival pathway in the bovine CL
      increasing luteal content of P(4) and PGE(2).

PMID- 19092987
TI  - The localization and expression of NADPH-diaphorase and isoforms of nitric oxide
      synthase in the porcine gravid uterus.
AB  - The aim of the present study was to investigate the localization and expression
      of NADPH-diaphorase (NADPH-d) as well as endothelial (eNOS) and inducible (iNOS)
      nitric oxide synthase isoforms in the porcine uterus on Days 20, 30, 40, 60, 75
      and 90 of gestation. The significant increase (p<0.001) in NADPH-d reaction was
      found in the trophoblast. The positive NADPH-d staining was also observed in the
      luminal and glandular epithelium and vascular endothelium. eNOS immunoreactivity
      was found in the endothelium of placental and maternal blood vessels, in the
      luminal epithelium and endometrial glands. The trophoblast displayed a slight
      increase in eNOS immunoreactivity starting from Day 20 of gestation. In
      comparison to eNOS, a stronger iNOS staining was found in the placental and
      endometrial blood vessels and in the trophoblast cells. Western blot analysis
      revealed a gradual increase in eNOS protein expression from Day 30 (p<0.001) and
      iNOS from Day 60 of gestation (p<0.001) in the placental zone. The significant
      increase in the NADPHd/iNOS expression after day 60 of gestation suggests a
      contribution of iNOS in uterine NO generation during the second half of
      pregnancy. A gradual increase in eNOS expression starting on Day 30 of pregnancy
      may indicate a synergistic, supportive effect on uterine vascular and myometrial
      contractility in pigs affecting the maintenance of the uterine quiescence.

PMID- 19092988
TI  - The feasibility of ultrasound biomicroscopy for non-invasive and sequential
      assessment of ovarian features in rodents.
AB  - The current study assessed the usefulness of in vivo high frequency ultrasound
      imaging (ultrasound biomicroscopy, UBM) for dynamic study of the ovarian
      structures in laboratory rodents. UBM imaging was performed, by using a 40 MHz
      probe, in 12 C57BL/6J female mice and four Wistars female rats at breeding age
      and during different reproductive periods. UBM provided outstanding images of
      both follicles and corpora lutea in cycling and non-cycling rats and mice and was
      useful to evaluate the ovarian response after controlled ovarian stimulation in
      the mouse. Thus, UBM may be a very useful method for reproductive studies in
      rodents.

PMID- 19092989
TI  - Reproductive parameters of common carp (Cyprinus carpio L) spawners during
      natural season and out-of-season spawning.
AB  - Common carp spawning characteristics were compared between season and out-of
      season periods. There were no differences in the percentage of ovulation,
      spermatozoa motility and embryo survival to the eyed-egg-stage between the
      spawning periods. Fish spawned during the season produced oocytes of higher total
      weight than those spawned out-of-season. On the day exogenous feeding began,
      larvae obtained in out-of-season spawning were shorter than those obtained during
      the spawning season. However, the out-of-season larvae started feeding two days
      earlier than in-season larvae. As a result, seven days after fertilization,
      larvae obtained during out-of-season had the same length as larvae obtained
      during season. It appears to be possible to obtain common carp larvae half a year
      before the natural spawning period without decreasing the quality of gametes and
      larvae.

PMID- 19092990
TI  - Progesterone receptor membrane component 1 (PGRMC1) gene expression in corpus
      luteum during the estrous cycle in cows.
AB  - The aim of the study was to investigate progesterone receptor membrane component
      1 (PGRMC1) mRNA expression in bovine corpus luteum (CL) obtained from heifers or
      non-pregnant cows on the following days of the estrous cycle: 1-5, 6-10, 11-16
      and 17-21 (n=4/each time period). The expression of PGRMC1 mRNA, analyzed by
      semiquantitative RT-PCR, was the highest on days 6-10 (p<0.01) and then it
      declined (p<0.05). The lowest expression was found on days 1-5 (p<0.05). A
      significant correlation (p<0.05) was also observed between luteal progesterone
      (P(4)) concentration and PGRMC1 mRNA expression. These data indicate that PGRMC1
      mRNA is expressed in bovine CL and this expression varies throughout the luteal
      phase. It is assumed that PGRMC1 may be involved in a non-genomic effect of P(4)
      on luteal cells.

PMID- 19092992
TI  - Anatomic landmarks for the first dorsal compartment.
AB  - OBJECTIVE: Knowledge of anatomic landmarks for the first dorsal compartment can
      assist clinicians with management of de Quervain's disease. The radial styloid,
      the scaphoid tubercle, and Lister's tubercle can be used as superficial landmarks
      for the first dorsal compartment. METHODS: Thirty-two cadaveric wrists were
      dissected, and measurements were taken from the predetermined landmarks to the
      extensor retinaculum. The compartments were also inspected for variability of the
      abductor pollicis longus tendon and intracompartmental septations. RESULTS: The
      average length of the extensor retinaculum from its proximal to distal extent
      measured approximately 2.2 cm. The distal aspect of the radial styloid was 0.3 cm
      distal to the distal aspect of the extensor retinaculum, and the distance between
      the distal aspect of the extensor retinaculum and the APL-Lister's-Scaphoid
      juncture was approximately 0.5 cm. A separate compartment for the extensor
      pollicis brevis was noted in 35% of the specimens. The abductor pollicis longus
      tendon demonstrated great variability with 1, 2, 3, or 4 slips in 9%, 30%, 43%,
      or 26% of the specimens, respectively. CONCLUSION: The superficial bony
      prominences of the radial wrist can be used reliably as anatomic landmarks for
      the first dorsal compartment.

PMID- 19092993
TI  - Ecological thresholds in the savanna landscape: developing a protocol for
      monitoring the change in composition and utilisation of large trees.
AB  - BACKGROUND: Acquiring greater understanding of the factors causing changes in
      vegetation structure -- particularly with the potential to cause regime shifts --
      is important in adaptively managed conservation areas. Large trees (> or =5 m in
      height) play an important ecosystem function, and are associated with a stable
      ecological state in the African savanna. There is concern that large tree
      densities are declining in a number of protected areas, including the Kruger
      National Park, South Africa. In this paper the results of a field study designed
      to monitor change in a savanna system are presented and discussed.
      METHODOLOGY/PRINCIPAL FINDINGS: Developing the first phase of a monitoring
      protocol to measure the change in tree species composition, density and size
      distribution, whilst also identifying factors driving change. A central issue is
      the discrete spatial distribution of large trees in the landscape, making point
      sampling approaches relatively ineffective. Accordingly, fourteen 10 m wide
      transects were aligned perpendicular to large rivers (3.0-6.6 km in length) and
      eight transects were located at fixed-point photographic locations (1.0-1.6 km in
      length). Using accumulation curves, we established that the majority of tree
      species were sampled within 3 km. Furthermore, the key ecological drivers (e.g.
      fire, herbivory, drought and disease) which influence large tree use and impact
      were also recorded within 3 km. CONCLUSIONS/SIGNIFICANCE: The technique presented
      provides an effective method for monitoring changes in large tree abundance, size
      distribution and use by the main ecological drivers across the savanna landscape.
      However, the monitoring of rare tree species would require individual marking
      approaches due to their low densities and specific habitat requirements. Repeat
      sampling intervals would vary depending on the factor of concern and proposed
      management mitigation. Once a monitoring protocol has been identified and
      evaluated, the next stage is to integrate that protocol into a decision-making
      system, which highlights potential leading indicators of change. Frequent
      monitoring would be required to establish the rate and direction of change. This
      approach may be useful in generating monitoring protocols for other dynamic
      systems.

PMID- 19092994
TI  - UP states protect ongoing cortical activity from thalamic inputs.
AB  - Cortical neurons in vitro and in vivo fluctuate spontaneously between two stable
      membrane potentials: a depolarized UP state and a hyperpolarized DOWN state. UP
      states temporally correspond with multineuronal firing sequences which may be
      important for information processing. To examine how thalamic inputs interact
      with ongoing cortical UP state activity, we used calcium imaging and targeted
      whole-cell recordings of activated neurons in thalamocortical slices of mouse
      somatosensory cortex. Whereas thalamic stimulation during DOWN states generated
      multineuronal, synchronized UP states, identical stimulation during UP states had
      no effect on the subthreshold membrane dynamics of the vast majority of cells or
      on ongoing multineuronal temporal patterns. Both thalamocortical and
      corticocortical PSPs were significantly reduced and neuronal input resistance was
      significantly decreased during cortical UP states -- mechanistically consistent
      with UP state insensitivity. Our results demonstrate that cortical dynamics
      during UP states are insensitive to thalamic inputs.

PMID- 19092996
TI  - Perinatal caffeine, acting on maternal adenosine A(1) receptors, causes long
      lasting behavioral changes in mouse offspring.
AB  - BACKGROUND: There are lingering concerns about caffeine consumption during
      pregnancy or the early postnatal period, partly because there may be long-lasting
      behavioral changes after caffeine exposure early in life. METHODOLOGY/PRINCIPAL
      FINDINGS: We show that pregnant wild type (WT) mice given modest doses of
      caffeine (0.3 g/l in drinking water) gave birth to offspring that as adults
      exhibited increased locomotor activity in an open field. The offspring also
      responded to cocaine challenge with greater locomotor activity than mice not
      perinatally exposed to caffeine. We performed the same behavioral experiments on
      mice heterozygous for adenosine A(1) receptor gene (A(1)RHz). In these mice
      signaling via adenosine A(1) receptors is reduced to about the same degree as
      after modest consumption of caffeine. A(1)RHz mice had a behavioral profile
      similar to WT mice perinatally exposed to caffeine. Furthermore, it appeared that
      the mother's genotype, not offspring's, was critical for behavioral changes in
      adult offspring. Thus, if the mother partially lacked A(1) receptors the
      offspring displayed more hyperactivity and responded more strongly to cocaine
      stimulation as adults than did mice of a WT mother, regardless of their genotype.
      This indicates that long-term behavioral alterations in the offspring result from
      the maternal effect of caffeine, and not a direct effect on fetus. WT offspring
      from WT mother but having a A(1)R Hz grandmother preserved higher locomotor
      response to cocaine. CONCLUSIONS/SIGNIFICANCE: We suggest that perinatal
      caffeine, by acting on adenosine A(1) receptors in the mother, causes long
      lasting behavioral changes in the offspring that even manifest themselves in the
      second generation.

PMID- 19092995
TI  - Bitter taste receptors influence glucose homeostasis.
AB  - TAS1R- and TAS2R-type taste receptors are expressed in the gustatory system,
      where they detect sweet- and bitter-tasting stimuli, respectively. These
      receptors are also expressed in subsets of cells within the mammalian
      gastrointestinal tract, where they mediate nutrient assimilation and endocrine
      responses. For example, sweeteners stimulate taste receptors on the surface of
      gut enteroendocrine L cells to elicit an increase in intracellular Ca(2+) and
      secretion of the incretin hormone glucagon-like peptide-1 (GLP-1), an important
      modulator of insulin biosynthesis and secretion. Because of the importance of
      taste receptors in the regulation of food intake and the alimentary responses to
      chemostimuli, we hypothesized that differences in taste receptor efficacy may
      impact glucose homeostasis. To address this issue, we initiated a candidate gene
      study within the Amish Family Diabetes Study and assessed the association of
      taste receptor variants with indicators of glucose dysregulation, including a
      diagnosis of type 2 diabetes mellitus and high levels of blood glucose and
      insulin during an oral glucose tolerance test. We report that a TAS2R haplotype
      is associated with altered glucose and insulin homeostasis. We also found that
      one SNP within this haplotype disrupts normal responses of a single receptor,
      TAS2R9, to its cognate ligands ofloxacin, procainamide and pirenzapine. Together,
      these findings suggest that a functionally compromised TAS2R receptor negatively
      impacts glucose homeostasis, providing an important link between alimentary
      chemosensation and metabolic disease.

PMID- 19092998
TI  - Polymorphisms in the regulatory region of the Cyclophilin A gene influence the
      susceptibility for HIV-1 infection.
AB  - BACKGROUND: Previous studies have demonstrated an association between
      polymorphisms in the regulatory regions of Cyclophilin A (CypA) and
      susceptibility to both HIV-1 infection and disease progression. Here we studied
      whether these polymorphisms are associated with susceptibility to HIV-1 infection
      and disease progression in the Amsterdam Cohort on HIV-1 infection and AIDS (ACS)
      in a group of men having sex with men (MSM) and drug users (DU).
      METHODOLOGY/PRINCIPAL FINDINGS: We screened participants of the ACS for the
      C1604G and A1650G polymorphisms in the regulatory regions of CypA. The prevalence
      of the 1650G allele was significantly higher in high risk seronegative MSM than
      in HIV-1 infected MSM. However, C1604G or A1650G were not associated with the
      clinical course of infection in MSM of the ACS. Interestingly, participants of
      the ACS-DU who carried the 1604G allele showed a significantly accelerated
      progression when viral RNA load above 10(4.5) copies per ml plasma was used as an
      endpoint in survival analysis. CONCLUSION/SIGNIFICANCE: The results obtained in
      this study suggest that the A1650G polymorphism in the regulatory region of the
      CypA gene may be associated with protection from HIV-1 infection, while the 1604G
      allele may have a weak association with the clinical course of infection in DU.

PMID- 19092997
TI  - Cytoplasmic CUG RNA foci are insufficient to elicit key DM1 features.
AB  - The genetic basis of myotonic dystrophy type I (DM1) is the expansion of a CTG
      tract located in the 3' untranslated region of DMPK. Expression of mutant RNAs
      encoding expanded CUG repeats plays a central role in the development of cardiac
      disease in DM1. Expanded CUG tracts form both nuclear and cytoplasmic aggregates,
      yet the relative significance of such aggregates in eliciting DM1 pathology is
      unclear. To test the pathophysiology of CUG repeat encoding RNAs, we developed
      and analyzed mice with cardiac-specific expression of a beta-galactosidase
      cassette in which a (CTG)(400) repeat tract was positioned 3' of the termination
      codon and 5' of the bovine growth hormone polyadenylation signal. In these
      animals CUG aggregates form exclusively in the cytoplasm of cardiac cells. A key
      pathological consequence of expanded CUG repeat RNA expression in DM1 is aberrant
      RNA splicing. Abnormal splicing results from the functional inactivation of
      MBNL1, which is hypothesized to occur due to MBNL1 sequestration in CUG foci or
      from elevated levels of CUG-BP1. We therefore tested the ability of cytoplasmic
      CUG foci to elicit these changes. Aggregation of CUG RNAs within the cytoplasm
      results both in Mbnl1 sequestration and in approximately a two fold increase in
      both nuclear and cytoplasmic Cug-bp1 levels. Significantly, despite these changes
      RNA splice defects were not observed and functional analysis revealed only subtle
      cardiac dysfunction, characterized by conduction defects that primarily manifest
      under anesthesia. Using a human myoblast culture system we show that this
      transgene, when expressed at similar levels to a second transgene, which encodes
      expanded CTG tracts and facilitates both nuclear focus formation and aberrant
      splicing, does not elicit aberrant splicing. Thus the lack of toxicity of
      cytoplasmic CUG foci does not appear to be a consequence of low expression
      levels. Our results therefore demonstrate that the cellular location of CUG RNA
      aggregates is an important variable that influences toxicity and support the
      hypothesis that small molecules that increase the rate of transport of the mutant
      DMPK RNA from the nucleus into the cytoplasm may significantly improve DM1
      pathology.

PMID- 19092999
TI  - Release of sICAM-1 in oocytes and in vitro fertilized human embryos.
AB  - BACKGROUND: During the last years, several studies have reported the significant
      relationship between the production of soluble HLA-G molecules (sHLA-G) by 48-72
      hours early embryos and an increased implantation rate in IVF protocols. As
      consequence, the detection of HLA-G modulation was suggested as a marker to
      identify the best embryos to be transferred. On the opposite, no suitable markers
      are available for the oocyte selection. METHODOLOGY/PRINCIPAL FINDINGS: The major
      finding of the present paper is that the release of ICAM-1 might be predictive of
      oocyte maturation. The results obtained are confirmed using three independent
      methodologies, such as ELISA, Bio-Plex assay and Western blotting. The sICAM-1
      release is very high in immature oocytes, decrease in mature oocytes and become
      even lower in in vitro fertilized embryos. No significant differences were
      observed in the levels of sICAM-1 release between immature oocytes with different
      morphological characteristics. On the contrary, when the mature oocytes were
      subdivided accordingly to morphological criteria, the mean sICAM-I levels in
      grade 1 oocytes were significantly decreased when compared to grade 2 and 3
      oocytes. CONCLUSIONS/SIGNIFICANCE: The reduction of the number of fertilized
      oocytes and transferred embryos represents the main target of assisted
      reproductive medicine. We propose sICAM-1 as a biochemical marker for oocyte
      maturation and grading, with a possible interesting rebound in assisted
      reproduction techniques.

PMID- 19093000
TI  - Reduced basal ATP synthetic flux of skeletal muscle in patients with previous
      acromegaly.
AB  - BACKGROUND: Impaired mitochondrial function and ectopic lipid deposition in
      skeletal muscle and liver have been linked to decreased insulin sensitivity. As
      growth hormone (GH) excess can reduce insulin sensitivity, we examined the impact
      of previous acromegaly (AM) on glucose metabolism, lipid storage and muscular ATP
      turnover. PARTICIPANTS AND METHODS: Seven AM (4f/3 m, age: 46+/-4 years, BMI:
      28+/-1 kg/m(2)) and healthy volunteers (CON: 3f/4 m, 43+/-4 years, 26+/-2
      kg/m(2)) matched for age and body mass underwent oral glucose testing for
      assessment of insulin sensitivity (OGIS) and ss-cell function (adaptation index,
      ADAP). Whole body oxidative capacity was measured with indirect calorimetry and
      spiroergometry. Unidirectional ATP synthetic flux (fATP) was assessed from (31)P
      magnetic resonance spectroscopy (MRS) of calf muscle. Lipid contents of tibialis
      anterior (IMCLt) and soleus muscles (IMCLs) and liver (HCL) were measured with
      (1)H MRS. RESULTS: Despite comparable GH, insulin-like growth factor-1 (IGF-I)
      and insulin sensitivity, AM had approximately 85% lower ADAP (p<0.01) and
      approximately 21% reduced VO(2)max (p<0.05). fATP was similarly approximately 25%
      lower in AM (p<0.05) and related positively to ADAP (r = 0.744, p<0.01), but
      negatively to BMI (r = -0.582, p<0.05). AM had approximately 3 fold higher HCL
      (p<0.05) while IMCLt and IMCLs did not differ between the groups. CONCLUSIONS:
      Humans with a history of acromegaly exhibit reduced insulin secretion, muscular
      ATP synthesis and oxidative capacity but elevated liver fat content. This
      suggests that alterations in ss-cell function and myocellular ATP production may
      persist despite normalization of GH secretion after successful treatment of
      acromegaly.

PMID- 19093001
TI  - Quantitative analysis of single nucleotide polymorphisms within copy number
      variation.
AB  - BACKGROUND: Single nucleotide polymorphisms (SNPs) have been used extensively in
      genetics and epidemiology studies. Traditionally, SNPs that did not pass the
      Hardy-Weinberg equilibrium (HWE) test were excluded from these analyses. Many
      investigators have addressed possible causes for departure from HWE, including
      genotyping errors, population admixture and segmental duplication. Recent large
      scale surveys have revealed abundant structural variations in the human genome,
      including copy number variations (CNVs). This suggests that a significant number
      of SNPs must be within these regions, which may cause deviation from HWE.
      RESULTS: We performed a Bayesian analysis on the potential effect of copy number
      variation, segmental duplication and genotyping errors on the behavior of SNPs.
      Our results suggest that copy number variation is a major factor of HWE violation
      for SNPs with a small minor allele frequency, when the sample size is large and
      the genotyping error rate is 0~1%. CONCLUSIONS: Our study provides the posterior
      probability that a SNP falls in a CNV or a segmental duplication, given the
      observed allele frequency of the SNP, sample size and the significance level of
      HWE testing.

PMID- 19093003
TI  - Rapid perceptual switching of a reversible biological figure.
AB  - Certain visual stimuli can give rise to contradictory perceptions. In this paper
      we examine the temporal dynamics of perceptual reversals experienced with
      biological motion, comparing these dynamics to those observed with other
      ambiguous structure from motion (SFM) stimuli. In our first experiment, naive
      observers monitored perceptual alternations with an ambiguous rotating walker, a
      figure that randomly alternates between walking in clockwise (CW) and counter
      clockwise (CCW) directions. While the number of reported reversals varied between
      observers, the observed dynamics (distribution of dominance durations, CW/CCW
      proportions) were comparable to those experienced with an ambiguous kinetic depth
      cylinder. In a second experiment, we compared reversal profiles with rotating and
      standard point-light walkers (i.e. non-rotating). Over multiple test repetitions,
      three out of four observers experienced consistently shorter mean percept
      durations with the rotating walker, suggesting that the added rotational
      component may speed up reversal rates with biomotion. For both stimuli, the drift
      in alternation rate across trial and across repetition was minimal. In our final
      experiment, we investigated whether reversals with the rotating walker and a non
      biological object with similar global dimensions (rotating cuboid) occur at
      random phases of the rotation cycle. We found evidence that some observers
      experience peaks in the distribution of response locations that are relatively
      stable across sessions. Using control data, we discuss the role of eye movements
      in the development of these reversal patterns, and the related role of exogenous
      stimulus characteristics. In summary, we have demonstrated that the temporal
      dynamics of reversal with biological motion are similar to other forms of
      ambiguous SFM. We conclude that perceptual switching with biological motion is a
      robust bistable phenomenon.

PMID- 19093002
TI  - CB1 expression is attenuated in Fallopian tube and decidua of women with ectopic
      pregnancy.
AB  - BACKGROUND: Embryo retention in the Fallopian tube (FT) is thought to lead to
      ectopic pregnancy (EP), a considerable cause of morbidity. In mice,
      genetic/pharmacological silencing of cannabinoid receptor Cnr1, encoding CB1,
      causes retention of embryos in the oviduct. The role of the endocannabinoids in
      tubal implantation in humans is not known. METHODS AND FINDINGS: Timed FT
      biopsies (n = 18) were collected from women undergoing gynecological procedures
      for benign conditions. Endometrial biopsies and whole blood were collected from
      women undergoing surgery for EP (n = 11); management of miscarriage (n = 6), and
      termination of pregnancy (n = 8). Using RT-PCR and immunohistochemistry, CB1 mRNA
      and protein expression levels/patterns were examined in FT and endometrial
      biopsies. The distribution of two polymorphisms of CNR1 was examined by TaqMan
      analysis of genomic DNA from the whole blood samples. In normal FT, CB1 mRNA was
      higher in luteal compared to follicular-phase (p<0.05). CB1 protein was located
      in smooth muscle of the wall and of endothelial vessels, and luminal epithelium
      of FT. In FT from women with EP, CB1 mRNA expression was low. CB1 mRNA expression
      was also significantly lower (p<0.05) in endometrium of women with EP compared to
      intrauterine pregnancies (IUP). Although of 1359G/A (rs1049353) polymorphisms of
      CNR1 gene suggests differential distribution of genotypes between the small,
      available cohorts of women with EP and those with IUP, results were not
      statistically significant. CONCLUSIONS: CB1 mRNA shows temporal variation in
      expression in human FT, likely regulated by progesterone. CB1 mRNA is expressed
      in low levels in both the FT and endometrium of women with EP. We propose that
      aberrant endocannabinoid-signaling in human FT leads to EP. Furthermore, our
      finding of reduced mRNA expression along with a possible association between
      polymorphism genotypes of the CNR1 gene and EP, suggests a possible genetic
      predisposition to EP that warrants replication in a larger sample pool.

PMID- 19093004
TI  - Safety and immunogenicity of a recombinant Plasmodium falciparum AMA1 malaria
      vaccine adjuvanted with Alhydrogel, Montanide ISA 720 or AS02.
AB  - BACKGROUND: Plasmodium falciparum Apical Membrane Antigen 1 (PfAMA1) is a
      candidate vaccine antigen expressed by merozoites and sporozoites. It plays a key
      role in red blood cell and hepatocyte invasion that can be blocked by antibodies.
      METHODOLOGY/PRINCIPAL FINDINGS: We assessed the safety and immunogenicity of
      recombinant PfAMA1 in a dose-escalating, phase Ia trial. PfAMA1 FVO strain,
      produced in Pichia pastoris, was reconstituted at 10 microg and 50 microg doses
      with three different adjuvants, Alhydrogel, Montanide ISA720 and AS02 Adjuvant
      System. Six randomised groups of healthy male volunteers, 8-10 volunteers each,
      were scheduled to receive three immunisations at 4-week intervals. Safety and
      immunogenicity data were collected over one year. Transient pain was the
      predominant injection site reaction (80-100%). Induration occurred in the
      Montanide 50 microg group, resulting in a sterile abscess in two volunteers.
      Systemic adverse events occurred mainly in the AS02 groups lasting for 1-2 days.
      Erythema was observed in 22% of Montanide and 59% of AS02 group volunteers. After
      the second dose, six volunteers in the AS02 group and one in the Montanide group
      who reported grade 3 erythema (>50 mm) were withdrawn as they met the stopping
      criteria. All adverse events resolved. There were no vaccine-related serious
      adverse events. Humoral responses were highest in the AS02 groups. Antibodies
      showed activity in an in vitro growth inhibition assay up to 80%. Upon
      stimulation with the vaccine, peripheral mononuclear cells from all groups
      proliferated and secreted IFNgamma and IL-5 cytokines. CONCLUSIONS/SIGNIFICANCE:
      All formulations showed distinct reactogenicity profiles. All formulations with
      PfAMA1 were immunogenic and induced functional antibodies. TRIAL REGISTRATION:
      (Clinicaltrials.gov) NCT00730782.

PMID- 19093005
TI  - Olig2-induced neural stem cell differentiation involves downregulation of Wnt
      signaling and induction of Dickkopf-1 expression.
AB  - Understanding stem cell-differentiation at the molecular level is important for
      clinical applications of stem cells and for finding new therapeutic approaches in
      the context of cancer stem cells. To investigate genome-wide changes involved in
      differentiation, we have used immortalized neural stem cell (NSC) line (HB1.F3)
      and Olig2-induced NSC differentiation model (F3.Olig2). Using microarray
      analysis, we revealed that Olig2-induced NSC differentiation involves
      downregulation of Wnt pathway, which was further confirmed by TOPflash/FOPflash
      reporter assay, RT-PCR analysis, immunoblots, and immunocytochemistry.
      Furthermore, we found that Olig2-induced differentiation induces the expression
      of Dickkopf-1(Dkk1), a potent antagonist of Wnt signaling. Dkk1 treatment blocked
      Wnt signaling in HB1.F3 in a dosage-dependent manner, and induced differentiation
      into astrocytes, oligodendrocytes, and neurons. Our results support cancer stem
      cell hypothesis which implies that signaling pathway for self-renewal and
      proliferation of stem cells is maintained till the late stage of differentiation.
      In our proposed model, Dkk1 may play an important role in downregulating self
      renewal and proliferation pathway of stem cells at the late stage of
      differentiation, and its failure may lead to carcinogenesis.

PMID- 19093006
TI  - Effect of TNF-alpha on human ARPE-19-secreted proteins.
AB  - PURPOSE: To identify cytokine-induced changes in the secretome of human retinal
      pigment epithelial (RPE) cells and their potential implication in age-related
      macular degeneration pathogenesis. METHODS: Stable isotope labeling by amino in
      cell culture (SILAC) was used in combination with liquid chromatography tandem
      mass spectrometry (LC-MS/MS) to measure differential protein secretion from tumor
      necrosis factor-alpha (TNF-alpha) treated ARPE-19 versus untreated ARPE-19 cells.
      Typically, one set of cells was subcultured in a medium in which Arg and Lys were
      replaced by (13)C(6)-Arg and (15)N(2,) (13)C(6)-Lys while the other set of cells
      was grown in unlabeled medium. The fully labeled cells were then treated with TNF
      alpha, while unlabeled cells were left untreated. Spent media from both treated
      and untreated cells were collected, mixed at 1:1 ratio, and processed for LC
      MS/MS analysis. Labeled and unlabeled peptide pairs were identified and their
      intensities were used to determine protein ratios in TNF-alpha treated cells
      versus untreated cells. To validate the data, we performed a reverse experiment
      in which unlabeled cells were treated with TNF-alpha while labeled cells were
      kept untreated. RESULTS: A total of 146 proteins were identified as putatively
      secreted proteins in the spent medium of ARPE-19 cells and only six among these
      were differentially secreted following TNF-alpha treatment. Secretion of
      complement 3 and sulfhydryl oxidase-1 was increased by twofold, fibronectin by
      1.7 fold, plasminogen activator inhibitor 1 by 1.9 fold and syndecan-4 by 4.35
      fold while secretion of trans-golgi network protein-2 was decreased by twofold.
      CONCLUSIONS: TNF-alpha modulates secretion of specific proteins in ARPE-19 cells.
      These proteins are involved in pathways relevant to AMD pathogenesis (e.g.,
      extracellular matrix remodeling, complement pathway, and angiogenesis).

PMID- 19093007
TI  - A novel mutation in BBS7 gene causes Bardet-Biedl syndrome in a Chinese family.
AB  - PURPOSE: To describe the clinical features of and identify a novel mutation in
      Bardet-Biedl syndrome 7 gene (BBS7) in a Chinese family. METHODS: Nineteen
      individuals at risk for inheriting Bardet-Biedl syndrome (BBS) in a Chinese
      family participated in the study. Physical examination was performed and blood
      was drawn for DNA extraction. Linkage analysis was conducted for all known BBS
      loci, and mutation screening of BBS7 gene and BBS12 gene was performed. RESULTS:
      A Chinese family with inherited BBS was identified. After performing linkage
      analysis on all 13 known loci, we found the disease phenotype of a Chinese family
      with BBS linked to a locus where BBS7 and BBS12 genes locate. CONCLUSIONS: This
      study describes a novel mutation in BBS7 causing BBS in a Chinese family. This is
      the first report that a mutation in a BBS gene causes BBS in a Chinese
      population. These results expand the spectrum of human disease associated with
      mutations of BBS7 since the initial three mutations in BBS7 were first identified
      in 2003.

PMID- 19093009
TI  - Clinical and genetic findings in Hungarian patients with X-linked juvenile
      retinoschisis.
AB  - PURPOSE: To determine clinical phenotypes, examine the age dependency of X-linked
      juvenile retinoschisis (XLRS), and identify mutations in the retinoschisis1 gene
      (RS1) in 13 Hungarian (Caucasian) families with this disease. METHODS: This study
      included 72 members in 13 families. Complete ophthalmological examinations,
      including optical coherence tomography (OCT) and full-field and multifocal
      electroretinography (ERG), were performed on 20 affected males, 13 female
      carriers, and 27 healthy controls. The patients were divided into two age groups
      (Group I <25 years and Group II >25 years), retrospectively, to assess the
      possible effects of age. Correlations among genotype, age, best corrected visual
      acuity (BCVA), OCT, and ERG results were analyzed. A modified classification
      scheme was done to identify the different phenotypes of the disease. In each of
      the 72 family members and 100 age-matched male controls, all exons and introns of
      RS1 were amplified by polymerase chain reaction (PCR) and directly sequenced.
      RESULTS: Foveal retinoschisis was detected in 25 eyes (62.5%) of patients by
      funduscopy, and in 29 eyes (72.5%) by OCT, while macular lamellar schisis was
      recognizable only by OCT in 30 eyes (75%) of patients. Foveal thickness (FT) and
      total macular volume were significantly increased in younger (Group I) patients
      only. For patients younger than 26 years, large inner nuclear central cysts were
      observable by OCT, while after 26 years, foveas were atrophic. White flecks and
      dots, which were like that seen in fundus albipunctatus, were detected in both
      eyes of one patient. In both patient groups, characteristically decreased b-waves
      of standard combined ERG were recorded without any significant difference between
      the patient groups. The BCVA and ERG parameters of all patients and the OCT of
      younger patients were significantly worse (p<0.05) than those of age-matched
      controls. A significant difference between the two age groups was found in case
      FT, total macular volume, and amplitudes of rod b-wave only. Moderate negative
      correlation (r=-0.54, p<0.001) was detected between age and FT, while only low
      negative correlation (r=-0.33, p<0.05) was detected between age and standard
      combined b-wave amplitudes of full-field ERG. BCVA LogMAR did not show any
      obvious correlation with age (r=-0.14, p=0.39) or with the type of mutation. Nine
      different mutations were identified in 25 male patients and 31 female carriers of
      13 families: six known and one novel missense mutation (c.575C>T, p.Pro192Leu),
      one insertion mutation (c.579dupC, p.Ile194Hisfs29ext43), and one frameshift,
      causing splice site mutation (c.78+1G>C) were detected. These mutations were
      absent in the 100 age-matched male control samples. CONCLUSIONS: Foveal cystic
      schisis was found more often by OCT than by funduscopy (+10%), while flat macular
      lamellar schisis was recognizable only by OCT. Advancing age inversely influenced
      the size of cavities (FT), and standard combined b-wave amplitudes of full-field
      ERG, while BCVA, response density, and implicit times of multifocal
      electroretinography did not show any obvious correlation with age. The atrophic
      stage of the disease was observable after 26 years of age. The lesions that
      appeared to be indicative of fundus albipunctatus were proven to be palisades
      between the splitted retinal layers. Our modified classification scheme was
      helpful in assessing the prevalence of disease types. In these Hungarian
      patients, one novel and eight known mutations were detected. The distribution of
      mutations in RS1 was different to that reported in the literature, because the
      greatest number of different mutations was in exon 6 instead of exon 4. Two
      mutation hot spots were found: between c.418-422 in exon 5 and between c.574-579
      in exon 6. Genotype-phenotype correlation was not demonstrable.

PMID- 19093008
TI  - Reprogramming chick RPE progeny cells to differentiate towards retinal neurons by
      ash1.
AB  - PURPOSE: Harnessing a cell culture of retinal pigment epithelium (RPE) to give
      rise to retinal neurons may offer a source of developing neurons for cell
      replacement studies. This study explores the possibility of reprogramming RPE
      progeny cells to differentiate toward retinal neurons with achaete-scute homolog
      1 (ash1), a proneural gene that is expressed in progenitor cells in the
      developing retina and promotes amacrine cell production when overexpressed in the
      chick retina. METHODS: Replication Competent Avian Splice (RCAS) retrovirus was
      used to drive the ectopic expression of ash1 in cell cultures of dissociated RPE
      isolated from day 6 chick embryos. RCAS expressing green fluorescent protein
      (RCAS-GFP) was used as control. The cultures were examined for de novo generation
      of neuron-like cells by molecular, cellular, and physiologic criteria. RESULTS:
      In control cultures infected with RCAS-GFP, RPE cells appeared cobblestone-like
      and often darkly pigmented. In cultures infected with RCAS-ash1, however, cells
      remained de-pigmented and frequently formed clusters. Further examination at the
      morphological and molecular levels showed the development of elaborate processes
      characteristic of neurons and the expression of genes/markers that identify
      different types of retinal neurons. The most prevalently expressed neural marker
      was calretinin, which in the chick retina identifies amacrine, ganglion, and
      horizontal cells. As an assay for functional maturation, the reprogrammed cells
      were analyzed for the presence of functional, ionotropic glutamate receptors that
      lead to a rise in the cytosolic free calcium (Ca(2+)) concentration. Calcium
      imaging showed that reprogrammed cells responded to glutamate and N-methyl-D
      aspartate (NMDA) by increasing their Ca(2+) concentrations, which, after reaching
      a peak level, returned to the basal level. The response curves of reprogrammed
      cells resembled those of cultured retinal neurons. CONCLUSIONS: These results
      suggest that RPE progeny cells can be reprogrammed by ash1 to develop molecular,
      morphological, and physiologic properties that are characteristic of retinal
      neurons.

PMID- 19093010
TI  - In vivo biopsy by laser confocal microscopy for evaluation of traumatic recurrent
      corneal erosion.
AB  - PURPOSE: Laser in vivo confocal microscopy noninvasively provides images that are
      equivalent to high quality histology. We have now applied this technique to
      identify pathological characteristics of traumatic recurrent corneal erosion
      (RCE). METHODS: Six eyes of six patients with traumatic RCE were studied. Corneas
      were examined with a slit lamp biomicroscope and with a laser in vivo confocal
      microscope (Heidelberg Retina Tomograph II-Rostock Cornea Module or HRTII-RCM) at
      various times after the onset of the most recent recurrence of corneal erosion.
      RESULTS: Brightly reflective granular structures were detected by the HRTII-RCM
      system in the basal and wing cell layers of the corneal epithelium in all eyes
      affected by recurrent erosion. Activated keratocytes and scattered fine particles
      were also apparent in the shallow stroma of five of the six affected eyes. These
      features were not observed in the normal cornea. CONCLUSIONS: The HRTII-RCM
      system allows detection of characteristic abnormal structures in the cornea of
      individuals with traumatic RCE. The presence of granular structures in the
      corneal epithelium as well as persistent inflammation in the shallow stroma may
      contribute to the deterioration of the corneal epithelial cell alignment and to
      the weakening of adhesion between the basal epithelial cells and the basement
      membrane in RCE lesions.

PMID- 19093017
TI  - Where credit is due.

PMID- 19093019
TI  - NIH Transformative R01 grant deadline approaches.

PMID- 19093018
TI  - Meetings of the minds: maximizing drug discovery.

PMID- 19093020
TI  - Allan Spradling wins 2008 Gruber Genetics Prize.

PMID- 19093022
TI  - MacArthur Foundation Fellowships.

PMID- 19093021
TI  - A new generation of superb models.

PMID- 19093023
TI  - The first transgenic mice: an interview with Mario Capecchi. Interview by Kristin
      Kain.

PMID- 19093024
TI  - Promoting translational research at Vanderbilt University's CTSA institute.

PMID- 19093025
TI  - Studying host-pathogen interactions and innate immunity in Caenorhabditis
      elegans.
AB  - The genetic analysis of mechanisms of pathogen resistance in the nematode
      Caenorhabditis elegans has revealed a role for evolutionarily conserved signaling
      pathways that are required for innate immunity in a wide range of organisms, from
      worms to mammals. C. elegans represents one of the more simple host organisms in
      which mechanisms of host defense can be dissected, and the use of C. elegans
      presents the researcher with a wide array of genetic and genomic tools to probe
      the host-pathogen interface. The study of host defense mechanisms in C. elegans
      continues to provide an ancient evolutionary perspective on innate immunity,
      which may generate insights into the conserved processes in phylogenetically
      diverse host organisms, including humans.

PMID- 19093026
TI  - Research on animal model organisms funded by the European Commission's framework
      programmes.
AB  - Recognising the crucial role of model organisms in exploring the causes of human
      disease and in developing safe treatments, the European Commission has invested
      euro180 million in collaborative research projects on model organisms since 2002.
      Further financial support is planned for the future. Projects supported by the
      European Commission are playing an important role in structuring the research
      landscape in Europe and creating the knowledge base to understand health and
      disease. Furthermore, they are generating important and freely available data
      and/or animal resources that will catalyse progress in biomedical research. This
      paper focuses on animal model organisms and includes the rodents, mouse and rat,
      other vertebrates such as zebrafish and frog, and also invertebrates such as
      nematodes. Research on other model organisms, including yeast, bacteria and
      plants, is also being supported and this is providing knowledge on basic cellular
      and molecular processes, as well as on host-microorganism interactions.

PMID- 19093027
TI  - Mouse models of allergic asthma: acute and chronic allergen challenge.
AB  - Asthma is defined as a chronic inflammatory disease of the airways; however, the
      underlying physiological and immunological processes are not fully understood.
      Animal models have been used to elucidate asthma pathophysiology, and to identify
      and evaluate novel therapeutic targets. Several recent review articles (Epstein,
      2004; Lloyd, 2007; Boyce and Austen, 2005; Zosky and Sly, 2007) have discussed
      the potential value of these models. Allergen challenge models reproduce many
      features of clinical asthma and have been widely used by investigators; however,
      the majority involve acute allergen challenge procedures. It is recognised that
      asthma is a chronic inflammatory disease resulting from continued or intermittent
      allergen exposure, usually via inhalation, and there has been a recent focus on
      developing chronic allergen exposure models, predominantly in mice. Here, we
      review the acute and chronic exposure mouse models, and consider their potential
      role and impact in the field of asthma research.

PMID- 19093028
TI  - Zebrafish myelination: a transparent model for remyelination?
AB  - There is currently an unmet need for a therapy that promotes the regenerative
      process of remyelination in central nervous system diseases, notably multiple
      sclerosis (MS). A high-throughput model is, therefore, required to screen
      potential therapeutic drugs and to refine genomic and proteomic data from MS
      lesions. Here, we review the value of the zebrafish (Danio rerio) larva as a
      model of the developmental process of myelination, describing the powerful
      applications of zebrafish for genetic manipulation and genetic screens, as well
      as some of the exciting imaging capabilities of this model. Finally, we discuss
      how a model of zebrafish myelination can be used as a high-throughput screening
      model to predict the effect of compounds on remyelination. We conclude that
      zebrafish provide a highly versatile myelination model. As more complex
      transgenic zebrafish lines are developed, it might soon be possible to visualise
      myelination, or even remyelination, in real time. However, experimental outputs
      must be designed carefully for such visual and temporal techniques.

PMID- 19093029
TI  - Peptidylarginine deiminase 2 (PAD2) overexpression in transgenic mice leads to
      myelin loss in the central nervous system.
AB  - Demyelination in the central nervous system is the hallmark feature in multiple
      sclerosis (MS). The mechanism resulting in destabilization of myelin is a complex
      multi-faceted process, part of which involves deimination of myelin basic protein
      (MBP). Deimination, the conversion of protein-bound arginine to citrulline, is
      mediated by the peptidylarginine deiminase (PAD) family of enzymes, of which the
      PAD2 and PAD4 isoforms are present in myelin. To test the hypothesis that PAD
      contributes to destabilization of myelin in MS, we developed a transgenic mouse
      line (PD2) containing multiple copies of the cDNA encoding PAD2, under the
      control of the MBP promoter. Using previously established criteria, clinical
      signs were more severe in PD2 mice than in their normal littermates. The increase
      in PAD2 expression and activity in white matter was demonstrated by
      immunohistochemistry, reverse transcriptase-PCR, enzyme activity assays, and
      increased deimination of MBP. Light and electron microscopy revealed more severe
      focal demyelination and thinner myelin in the PD2 homozygous mice compared with
      heterozygous PD2 mice. Quantitation of the disease-associated molecules GFAP and
      CD68, as measured by immunoslot blots, were indicative of astrocytosis and
      macrophage activation. Concurrently, elevated levels of the pro-inflammatory
      cytokine TNF-alpha and nuclear histone deimination support initiation of
      demyelination by increased PAD activity. These data support the hypothesis that
      elevated PAD levels in white matter represents an early change that precedes
      demyelination.

PMID- 19093031
TI  - Analysis of mouse models carrying the I26T and R160C substitutions in the
      transcriptional repressor HESX1 as models for septo-optic dysplasia and
      hypopituitarism.
AB  - A homozygous substitution of the highly conserved isoleucine at position 26 by
      threonine (I26T) in the transcriptional repressor HESX1 has been associated with
      anterior pituitary hypoplasia in a human patient, with no forebrain or eye
      defects. Two individuals carrying a homozygous substitution of the conserved
      arginine at position 160 by cysteine (R160C) manifest septo-optic dysplasia
      (SOD), a condition characterised by pituitary abnormalities associated with
      midline telencephalic structure defects and optic nerve hypoplasia. We have
      generated two knock-in mouse models containing either the I26T or R160C
      substitution in the genomic locus. Hesx1(I26T/I26T) embryos show pituitary
      defects comparable with Hesx1(-/-) mouse mutants, with frequent occurrence of
      ocular abnormalities, although the telencephalon develops normally.
      Hesx1(R160C/R160C) mutants display forebrain and pituitary defects that are
      identical to those observed in Hesx1(-/-) null mice. We also show that the
      expression pattern of HESX1 during early human development is very similar to
      that described in the mouse, suggesting that the function of HESX1 is conserved
      between the two species. Together, these results suggest that the I26T mutation
      yields a hypomorphic allele, whereas R160C produces a null allele and,
      consequently, a more severe phenotype in both mice and humans.

PMID- 19093033
TI  - Adaptive genetic variation, stress and glucose regulation.
AB  - Elevated glucose levels in the presence of insulin are indicative of type 2
      diabetes and the more inclusive metabolic syndrome. Alleles conferring
      susceptibility to these and other common conditions may be adaptations to past
      environments. It is possible that other mammals exhibiting environmental
      diversity harbor similar variants; therefore, we assessed glucose regulation in
      two species of deer mice (Peromyscus), a diverse endemic North American group.
      The prairie deer mouse, P. maniculatus bairdii (BW), and the Oldfield mouse, P.
      polionotus subgriseus (PO) differ in sexual dimorphism, behavior and habitat. PO
      animals exhibit better regulatory ability than BW animals, particularly among
      males, although both species display equivalent insulin levels/responses and non
      fasted glucose levels. Hybrid males exhibit a PO glucose challenge response and
      subsequent analysis of consomic animals implicates Y chromosome variation as the
      genetic cause. Two pieces of evidence indicate that the male glucose regulatory
      differences are mediated by stress response: (1) fasting and handling alone
      account for most of the variation; (2) an inhibitor of glucocorticoid (GC) stress
      hormone synthesis eliminates these differences. PO males have GC levels that are
      twice those of BW males, indicating the presence of alleles that attenuate the GC
      response. We hypothesize that the interspecific physiological and behavioral
      differences are interrelated and that similar human variants exist.

PMID- 19093039
TI  - Activity of superoxide dismutase obtained from senile cataract lens - effect of
      diabetes mellitus.
AB  - The activity of Cu,Zn superoxide dismutase in the fluid obtained from eye lens
      capsules after cataract surgery was investigated in samples obtained from
      patients with senile cataract and with senile cataract combined with diabetes
      mellitus. Two parameters were measured and compared: the frequency of occurrence
      of detected superoxide dismutase activity and the relative activity of the enzyme
      in samples derived from senile cataract patients versus those from the patients
      affected additionally by diabetes mellitus. It was confirmed that the decrease of
      superoxide dismutase activity during cataract was additionally promoted by
      diabetes mellitus.

PMID- 19093035
TI  - Epithelial-to-mesenchymal transition of peritoneal mesothelial cells is regulated
      by an ERK/NF-kappaB/Snail1 pathway.
AB  - Epithelial-to-mesenchymal transition (EMT) occurs in fibrotic diseases affecting
      the kidney, liver and lung, and in the peritoneum of patients undergoing
      peritoneal dialysis. EMT in the peritoneum is linked to peritoneal membrane
      dysfunction, and its establishment limits the effectiveness of peritoneal
      dialysis. The molecular regulation of EMT in the peritoneum is thus of interest
      from basic and clinical perspectives. Treatment of primary human mesothelial
      cells (MCs) with effluent from patients undergoing peritoneal dialysis induced a
      genuine EMT, characterized by downregulated E-cadherin and cytokeratin
      expression, cell scattering, and spindle-like morphology. This EMT was replicated
      by co-stimulation with transforming growth factor (TGF)-beta1 and interleukin
      (IL)-1beta. Retroviral overexpression of a mutant inhibitor of kappaB (IkappaB)
      demonstrated that NF-kappaB activation is required for E-cadherin and cytokeratin
      downregulation during EMT. Pre-treatment with the MAP kinase kinase (MEK)-1/2
      inhibitor U0126 showed that cytokine-triggered NF-kappaB nuclear translocation
      and transcriptional activity are mediated by activation of extracellular
      regulated kinase (ERK). Cytokine-mediated induction of mRNA expression of the
      transcription factor Snail1, a repressor of E-cadherin expression and a potent
      inducer of EMT, was prevented by blockade of ERK or NF-kappaB. Finally, blockade
      of ERK/NF-kappaB signaling in ex vivo MCs that were cultured from peritoneal
      dialysis effluents reverted cells to an epithelioid morphology, upregulated E
      cadherin and cytokeratin expression, and downregulated Snail1 expression.
      Modulation of the ERK/NF-kappaB/Snail1 pathway may provide a means of
      counteracting the progressive structural and functional deterioration of the
      peritoneal membrane during peritoneal dialysis.

PMID- 19093037
TI  - Combinatorial interaction between CCM pathway genes precipitates hemorrhagic
      stroke.
AB  - Intracranial hemorrhage (ICH) is a particularly severe form of stroke whose
      etiology remains poorly understood, with a highly variable appearance and onset
      of the disease (Felbor et al., 2006; Frizzell, 2005; Lucas et al., 2003). In
      humans, mutations in any one of three CCM genes causes an autosomal dominant
      genetic ICH disorder characterized by cerebral cavernous malformations (CCM).
      Recent evidence highlighting multiple interactions between the three CCM gene
      products and other proteins regulating endothelial junctional integrity suggests
      that minor deficits in these other proteins could potentially predispose to, or
      help to initiate, CCM, and that combinations of otherwise silent genetic deficits
      in both the CCM and interacting proteins might explain some of the variability in
      penetrance and expressivity of human ICH disorders. Here, we test this idea by
      combined knockdown of CCM pathway genes in zebrafish. Reducing the function of
      rap1b, which encodes a Ras GTPase effector protein for CCM1/Krit1, disrupts
      endothelial junctions in vivo and in vitro, showing it is a crucial player in the
      CCM pathway. Importantly, a minor reduction of Rap1b in combination with similar
      reductions in the products of other CCM pathway genes results in a high incidence
      of ICH. These findings support the idea that minor polygenic deficits in the CCM
      pathway can strongly synergize to initiate ICH.

PMID- 19093040
TI  - Reversal of drug resistance by silencing Survivin gene expression in acute
      myeloid leukemia cells.
AB  - The role of Survivin in the pathogenesis of leukemia was explored in order to
      discover the effective avenues for gene therapy. Most primary leukemia cells
      isolated from patients as well as three leukemia cell lines (HL-60, K562, and
      U937) all expressed Survivin gene. To investigate the relationship between
      Survivin and chemotherapeutic resistance, HL-60 cells were treated with
      daunorubicin (DNR), mitoxantrone (MIT) or arsenious oxide (As(2)O(3)), and it was
      found that after 24 h the level of Survivin mRNA was decreased by 9.7%, 41.0% and
      27.5%, respectively. At 72 h, the level of Survivin mRNA was increased by 21.2%
      and 65.2% in HL-60 cells treated with DNR or MIT, but decreased by 33.2% in those
      treated with As(2)O(3) as compared with that in the cells treated for 24 h. These
      results showed that DNR and MIT could initally decrease the expression of
      Survivin and then increase it, but As(2)O(3) could decrease the Survivin
      expression continually. Furthermore, shRNA plasmids targeting the Survivin gene
      (pEGFP-Survivin), which can silence the expression of Survivin with a high
      specificity, were constructed. pEGFP-Survivin and pEGFP-H1 were transfected into
      HL-60 cells via electroporation and selected by G418, and HL-60/Survivin and HL
      60/EGFP cells were obtained. After treatment with DNR, the cell survival rate and
      IC(50) of DNR in HL-60/Survivin cells were decreased substantially as compared
      with those of HL-60/EGFP and HL-60 cells (IC(50) of DNR: 18.3 +/- 2.45 vs 40.8 +/
      6.37 and 39.2 +/- 5.91 ng/ml, respectively), and the apoptosis rate was elevated
      ((84.3 +/- 19.7)% vs (45.8 +/- 13.8)% and (50.9 +/- 12.4)%, respectively). These
      results suggest that shRNA can down-regulate the expression of Survivin in HL-60
      cells substantially and improve their sensitivity to DNR. They also further
      explain the pathogenesis of leukemia drug resistance and provide new theory in
      the design of clinical therapies.

PMID- 19093042
TI  - The dentist in society part 5: a meaningful professional journey.

PMID- 19093041
TI  - [Latin-American Consensus on Difficult-to-Control Asthma. 2008 Update].
AB  - Asthma, which is more of a syndrome than a disease, usually responds to inhaled
      corticosteroid treatment, with or without the addition of long-acting beta
      agonists. However, in a certain group of patients asthma cannot be controlled
      despite administering appropriate drugs at high doses. Difficult-to-control
      asthma cases are the target of this consensus meeting. Clinical practice
      guidelines and consensus on this subject already exist, so we must emphasize that
      the objective of this document is to review said guidelines and adapt them to
      regional situations. It is also necessary to update the guidelines, as new
      treatment alternatives have appeared in our countries. Difficult-to-control
      asthma has many different names, such as severe, serious, difficult, refractory,
      unstable, life-threatening, corticoid-resistant, and corticoid-dependent asthma,
      among others. The prevalence of difficult-to-control asthma has not clearly been
      established, but several publications estimate it to represent 5% of the asthma
      population. However, the significant impact on asthma-related direct and indirect
      costs and the quality of life impairment in this patient population have been
      clearly shown. The Latin American Consensus on Difficult-to-Control Asthma
      submits the following definition: "Inadequately-controlled asthma existing
      despite appropriate treatment strategy adjusted to the clinical severity level
      (level 4 or higher of the Global Initiative for Asthma [GINA]), indicated by a
      physician and administered for at least six months". The correct diagnosis of
      difficult-to-control asthma usually is made when there is no response to adequate
      treatment adjusted to the clinical severity level. However, many conditions can
      mimic difficult-to-control asthma, while others can exacerbate it. Therefore, in
      order to ensure a correct diagnosis, certain requirements - systematic
      assessments - must be met which confirm the asthma diagnosis and rule out other
      conditions. The therapeutic approach to difficult-to-control asthma includes
      pharmacological and non-pharmacological aspects. Patient assessment and treatment
      should be conducted at appropriately-equipped sites and by specialists
      experienced in this field. In terms of drug therapy, we specifically looked at
      the position described in the guidelines regarding the different treatment
      options. At level 5 of its treatment strategy, GINA recommends adding oral
      glucocorticoids or omalizumab, albeit this combination is associated with serious
      undesirable effects, as per GINA itself. The recent Expert Panel Report 3 (2007)
      from the National Asthma Education and Prevention Program (NAEPP) proposes a
      different strategy. The treatment approach is divided into six levels: omalizumab
      is recommended as additional therapy at level 5 in patients with allergic asthma
      caused by perennial allergens, while oral corticoids are indicated at level 6 and
      can be used in combination with all level 5 control medications. Patients with
      difficult-to-control asthma require close follow-up with frequent reviews of
      their clinical and therapeutic condition and must have a written tailored action
      plan based on their asthma symptoms and home peak expiratory flow results.

PMID- 19093043
TI  - Two prosthetic crowns supported by a single implant: an esthetic alternative for
      restoring the anterior maxilla.
AB  - Esthetic complications due to nonharmonious peri-implant soft tissue profiles are
      common in the anterior maxilla, especially when 2 adjacent implants are found.
      This article suggests the use of a single implant to replace 2 lost adjacent
      teeth in this region and demonstrates the treatment with 2 clinical cases. The
      main advantage is preservation of the interdental papilla and gingival contours,
      compensating for the alveolar bone crest resorption at the platform of a second
      implant.

PMID- 19093044
TI  - Evaluation of vertical accuracy of interocclusal recording materials.
AB  - OBJECTIVE: To evaluate 4 interocclusal recording materials for their ability to
      reproduce accurately interocclusal relationships after a storage time of 1 or 48
      hours. METHOD AND MATERIALS: A custom-made metal apparatus was used to simulate
      the maxilla and mandible. The vertical discrepancies were measured by a precision
      dial gauge. Eight inter-occlusal records were made in each of the following
      groups: (G1) Futar D (polyvinyl siloxane; Kettenbach), (G2) Ramitec (polyether;
      3M ESPE), (G3) LuxaBite (composite resin based on bisacryl; DMG), (G4) Aluwax
      (aluminum wax; Aluwax Dental Products), (G5) LuxaBite corrected with LuxaBite,
      and (G6) LuxaBite corrected with Aluwax. The vertical discrepancies were measured
      after storage of the records for 1 and 48 hours at room temperature and
      repositioning of the records in the metal apparatus. Data were statistically
      analyzed using 1-way analysis of variance followed by the Games-Howell test (P <
      or = .05). RESULTS: After storage times of 1 and 48 hours, respectively, the mean
      vertical discrepancies (microm) for G1 (23/33) and G2 (25/30) were statistically
      significantly lower than for G3 (431/745) and G4 (110/151) (P < .05) but higher
      than for G5 (8/16) and G6 (7/17). There was no statistically significant
      difference between G1 and G2 or between G5 and G6 for either measurement.
      CONCLUSION: These vertical discrepancies increased after a storage time of 48
      hours. However, correction of the LuxaBite records with LuxaBite or Aluwax showed
      significantly lower vertical discrepancies than all other materials. Clinically,
      the vertical discrepancies the corrected records caused could be insignificant.

PMID- 19093045
TI  - Knoop hardness depth profile of polyacid-modified composite resins.
AB  - OBJECTIVES: To determine the hardness versus depth profile of several polyacid
      modified composite resins (PAM-Cs) as a function of shade (A2, A4) and compare
      the depth of cure (DoC) based on these profiles with that previously obtained
      with the scraping and penetrometer methods. METHOD AND MATERIALS: Samples of 6
      PAM-Cs (Hytac, 3M ESPE; F2000, 3M ESPE; Glasiosite, Voco; Dyract, Dentsply
      DeTrey; Dyract AP, Dentsply DeTrey; Compoglass F, Vivadent) and 3 composite
      resins (Herculite Enamel XRV, Kerr; Z100, 3M ESPE; Durafill VS, Heraeus Kulzer)
      with shades A2 and A4 were light-cured in bulk in split stainless steel molds
      (thickness ranging from 0.5 to 3.5 mm in steps of 0.5 mm). The Knoop hardness of
      the irradiated top (KHN(surface)) and nonirradiated bottom (KHN(bottom)) surfaces
      was determined as a function of sample thickness using a microhardness tester.
      RESULTS: Regression analysis demonstrated that for a given material, KHN(bottom)
      equals KHN(surface) up to a specific depth (= DoC) depending on the material and
      shade and then decreases linearly with increasing depth. The decrease of the KHN
      per unit depth differs significantly among materials and shades. According to a
      regression analysis, the scraping and penetrometer methods overestimate the DoC
      of PAM-Cs compared to the method based on the change of the hardness indentation
      with depth. CONCLUSIONS: Shade A2 results in greater values of DoC than shade A4,
      the effect depending quantitatively on the formulation of the material. Some
      formulations of PAM-Cs do not reach a DoC of 2 mm, a layer recommended to be
      applied in the incremental technique. The DoC as determined according to ISO
      4049:2000 apparently is based on a lower degree of polymerization corresponding
      to a KHN of 80% of the irradiated surface.

PMID- 19093046
TI  - Accidental extrusion of sodium hypochlorite into the maxillary sinus.
AB  - An unusual case is reported of accidental extrusion of sodium hypochlorite
      solution into the maxillary sinus during instrumentation in the course of root
      canal treatment of a maxillary premolar. This caused a burning sensation
      accompanied by nasal bleeding, swallowing of blood, and interrupted breathing.
      The case was managed by irrigating with sterile saline, arresting nasal bleeding,
      and administering antibiotics, anti-inflammatory drugs, and decongestants.

PMID- 19093047
TI  - An epidemiologic study of lip and palate clefts from a Brazilian reference
      hospital.
AB  - OBJECTIVE: To investigate the distribution of several types of clefts among
      adolescents and adults receiving treatment at the Center for Rehabilitation of
      Craniofacial Anomalies, Unifenas, Minas Gerais State, Brazil. METHODS AND
      MATERIALS: A total 154 untreated patients of low socioeconomic means with cleft
      lips and/or palates, without additional malformations, who came to the Center for
      Rehabilitation of Craniofacial Anomalies for treatment were analyzed, and
      clinical and socioeconomic variables were detailed. RESULTS: A predominance of
      complete cleft lip and palate, either unilateral or bilateral, was observed
      (52.60%), followed by isolated cleft lip (33.12%) and isolated cleft palate
      (14.28%). A discrete relationship between cleft palate and the female gender was
      noticed, and males were more affected by other types of clefts. CONCLUSIONS: Non
      Caucasian males with unilateral complete cleft lip and palate constituted the
      main profile of affected individuals.

PMID- 19093048
TI  - Septic pulmonary embolism secondary to dental focus.
AB  - A 24-year-old female was admitted to an infectious diseases unit with complaints
      of dyspnea and fever. She had suffered from multiple episodes of fever for 1
      year. The diagnostic workup revealed multiple pulmonary nodules on the chest CT
      scan, suggesting septic pulmonary embolism, and a periapical abscess around the
      maxillary right central incisor. Because no other infectious source was found and
      resolution of the fever and the pulmonary lesions occurred only after extraction
      of the affected tooth and antibiotic therapy, the condition was diagnosed as a
      periapical abscess complicated by septic pulmonary embolism.

PMID- 19093049
TI  - Clinical performance of the posterior composite QuiXfil after 3, 6, and 18 months
      in Class 1 and 2 cavities.
AB  - OBJECTIVE: This longitudinal randomized controlled clinical trial evaluated
      direct composite restorations for clinical acceptability of posterior
      restoratives in single- or multisurface cavities and provided a preliminary
      survey of the 3-, 6-, and 18-month results. METHOD AND MATERIALS: Three
      clinicians placed 46 QuiXfil (Xeno III; Dentsply DeTrey) and 50 Tetric Ceram
      (Syntac Classic; Vivadent) composite restorations in stress-bearing Class 1 and 2
      cavities in first or second molars (43 adult patients). Clinical evaluation was
      performed at baseline and after 3, 6, and 18 months by 2 other clinicians using
      modified US Public Health Service criteria. At the final recall period, 45
      QuiXfil and 49 Tetric Ceram restorations were assessed. RESULTS: A total of 97.8%
      of QuiXfil and 100% of Tetric Ceram posterior composites were assessed to be
      clinically excellent or acceptable with predominating Alpha scores. At the 18
      month recall, 1 QuiXfil restoration had failed because of bulk fracture. No
      significant differences between either composite could be detected at 18 months
      for all evaluated clinical criteria (P > .05). Small QuiXfil restorations
      exhibited significantly less marginal discoloration (P = .003) and better
      restoration integrity (P = .008) than large restorations. The comparison of
      restoration performance with time within both groups yielded a significant
      increase in marginal discoloration for QuiXfil (P = .011) and significant
      deterioration for anatomic form at the marginal step for Tetric Ceram (P = .011).
      However, both changes were only effects of scoring shifts from Alpha to Bravo.
      CONCLUSION: Clinical assessment of stress-bearing QuiXfil and Tetric Ceram
      posterior composite restorations exhibited for both materials good clinical
      results with predominating Alpha scores.

PMID- 19093050
TI  - Extraoral removal of a transmigrant mandibular canine associated with a
      dentigerous cyst.
AB  - Although the maxillary permanent canine is frequently misplaced, misplacement of
      the mandibular canine is a comparatively rare event. Pre-eruptive migration of a
      tooth across the midline is called transmigration. This condition has not been
      reported for teeth other than canines. Dentigerous cysts can involve any tooth,
      but mandibular canines are rarely affected like premolars and molars. Odontogenic
      cysts associated with impacted teeth are usually removed through an intraoral
      approach. However, on rare occasion, an extraoral approach is required to remove
      these lesions. A case of transmigrant mandibular canine associated with a
      dentigerous cyst that required an extraoral submental approach for removal is
      presented.

PMID- 19093051
TI  - The effect of a mild increase in temperature on tooth bleaching.
AB  - OBJECTIVE: To evaluate the effect of temperature on external tooth bleaching.
      METHOD AND MATERIALS: Human molars and premolars were internally stained and
      assessed using a standardized tea solution. The mesial aspects of the teeth were
      assigned to the treatment group (bleaching at 45 degrees C), and the distal
      aspects of the teeth were assigned to the control group (bleaching at 37 degrees
      C). An electronic chromometer with a tristimulus color analyzer was used to
      measure color change. The mean changes in the values of L*, a*, and b* from
      baseline to posttreatment were recorded, as were the overall color differences of
      the specimens in each group (DeltaE*). RESULTS: Increasing the temperature to 45
      degrees C significantly (P < .05) increased the bleaching efficacy and reduced
      the time needed to gain a lighter tooth shade. CONCLUSION: A controlled increase
      in the temperature of the bleaching agent might be useful in achieving better
      tooth bleaching in a shorter period of time.

PMID- 19093052
TI  - Adenomatoid odontogenic tumor: an unusual case exhibiting cribriform aspect.
AB  - The occurrence of areas exhibiting cribriform morphology in odontogenic tumors is
      not a very frequent finding. This report describes the case of a 22-year-old man
      who presented with swelling in the left anterior maxilla. An excisional biopsy
      was performed under local anesthesia. Histopathologically, the lesion consisted
      of a cystic wall exhibiting an odontogenic epithelium lining composed of oval,
      angular, and elongated cells forming a cribriform pattern. No recurrence has been
      detected after 2 years.

PMID- 19093054
TI  - The dentist in society-- part 6: postscript.

PMID- 19093053
TI  - Radiographic diagnostics: Eosinophilic granuloma of the mandible.

PMID- 19093055
TI  - Updated implant-retained restorative solutions in patients with hypodontia.
AB  - Hypodontia is often found during orthodontic screening and occurs with a
      prevalence of between 5% and 10%. One or more congenitally missing permanent
      teeth is a clinical finding that affects both male and female patients. Although
      maintaining deciduous teeth is an option in a few cases, the majority of patients
      with agenesis of teeth require extraction and orthodontic space closure or
      restorative treatment. Depending on the number and location of missing teeth,
      implant-supported fixed single-tooth restorations provide excellent long-term
      results. Choosing appropriate treatment techniques and materials will result in
      long-term clinical function, stability, and esthetic success.

PMID- 19093056
TI  - Do mandibular implant overdentures and conventional complete dentures meet the
      expectations of edentulous patients?
AB  - OBJECTIVES: To measure expectations of satisfaction with implant and conventional
      denture treatment in 2 groups of edentulous people and compare them with their
      resultant ratings of satisfaction to determine if either treatment meets the
      pretreatment expectation. METHOD AND MATERIALS: One hundred sixty-two edentulous
      middle-aged (MA, n = 102) and senior (S, n = 60) patients were enrolled in 2
      trials and, after randomization, received either a mandibular 2-implant
      overdenture (IOD) or a new conventional denture (CD). Before randomization, each
      subject rated their satisfaction with their current denture and expectations of
      satisfaction with both IOD and CD treatment on 100-mm visual analog scales (VAS).
      Six months posttreatment, all rated their satisfaction with their new prostheses
      on similar VAS. Expectations and satisfaction with treatment were compared.
      RESULTS: Posttreatment satisfaction with CD treatment was significantly lower
      than pretreatment expected satisfaction in both study populations (MA, P < .0001;
      S, P = .036). There was no (or only borderline) significant difference between
      pretreatment expectation and posttreatment satisfaction for patients receiving
      IODs in both study populations (MA, P = .078; S, P = .057). CONCLUSION:
      Posttreatment CD satisfaction failed to meet patients' pretreatment expectations
      of satisfaction; this was not the case for IODs, for which expectations were
      largely met.

PMID- 19093057
TI  - The use of 2 antibiotic regimens in aggressive periodontitis: comparison of
      changes in clinical parameters and gingival crevicular fluid biomarkers.
AB  - OBJECTIVES: To evaluate and compare the effect of nonsurgical periodontal therapy
      in conjunction with 2 different antibacterial agents on clinical and
      immunological parameters in aggressive periodontitis (AgP) patients. METHOD AND
      MATERIALS: Thirty-one AgP patients underwent clinical examination that included
      plaque index (PI), gingival index (GI), probing pocket depth (PPD), and clinical
      attachment level (CAL). GCF (gingival crevicular fluid) samples were collected
      and assayed for PGE(2), IL-1beta, and TNFalpha. Nonsurgical periodontal therapy
      was performed. The patients received doxycycline (doxy group) or metronidazole
      plus amoxicillin (am-met group). After completion of the mechanical phase of
      therapy, patients were seen biweekly for oral hygiene reinforcement. After 12
      weeks, clinical measurements and GCF sampling were repeated. RESULTS: The
      combined mechanical and antimicrobial therapy resulted in overall improvement in
      all clinical parameters; mean PPD reduction of 0.74 +/- 0.1 mm and mean CAL gain
      0.86 +/- 0.1 mm were both statistically significant (P = .0001). Marked reduction
      was observed for PGE2 and IL-1beta, but not TNFalpha. There was no significant
      difference between the 2 groups at baseline or final examination, except for
      PGE(2) at final examination: It was significantly lower for the doxy group (83.61
      +/- 5.8 ng) than for the am-met group (124.08 +/- 15.8 ng), P = .0202.
      CONCLUSION: Both treatment protocols resulted in significant improvements in the
      clinical and immunological parameters. When combined mechanical and antimicrobial
      protocol is desired and microbial cultures are not available, the use of both
      antibiotic regimens is recommended; the treatment of choice should be based on
      compliance, allergies, and potential side effects.

PMID- 19093058
TI  - Oculofaciocardiodental syndrome: report of a rare case.
AB  - Oculofaciocardiodental syndrome is a very rare multiple congenital anomaly
      syndrome characterized by congenital cataracts, multiple minor facial dysmorphic
      features, congenital heart defects, and dental anomalies including canine
      radiculomegaly and oligodontia. It is unrecognized by many medical and dental
      professionals. Oculofaciocardiodental syndrome is inherited as an X-linked
      dominant condition and is lethal in males. Only 20 cases have been documented to
      date. The present case is that of an affected female who had congenital
      cataracts, microphthalmia, characteristic dental anomalies, and typical facial
      dysmorphism.

PMID- 19093059
TI  - In vitro reduction of mutans streptococci by means of ozone gas application.
AB  - OBJECTIVE: To evaluate, in vitro, the antimicrobial effect of ozone gas on
      strains of reference mutans streptococci and strains isolated from children at a
      high risk of developing caries. METHOD AND MATERIALS: A series of dilutions was
      obtained from a total of 41 strains, and the effect of ozone was determined for
      applications of 10, 20, and 40 seconds, as well as a control, in terms of the
      reduction of viable bacteria. RESULTS: Ozone application for 10 and 20 seconds
      produced a significant reduction in the number of bacteria, inversely
      proportional to the bacterial concentration. When exposure lasted 40 seconds, no
      viable bacteria were obtained. CONCLUSIONS: Both time of application and initial
      bacterial concentration bear an influence on the antimicrobial effect of ozone on
      mutans streptococci.

PMID- 19093060
TI  - Flexural strength and hardness of reline and denture base acrylic resins after
      different exposure times of microwave disinfection.
AB  - OBJECTIVES: To evaluate the effect of microwave disinfection on the flexural
      strength and Vickers hardness of 4 autopolymerized resins (Kooliner [K], Tokuso
      Rebase Fast [T], Ufi Gel Hard [U], and New Truliner [N]) and 1 denture base resin
      (Lucitone 550 [L]). METHOD AND MATERIALS: For each material, 48 specimens (64 x
      10 x 3.3 mm) were made and divided into 6 equal groups (n = 8). In the control
      group, specimens were untreated. Before testing, specimens were immersed in 200
      mL of distilled water and submitted to disinfection for 1 of the following
      irradiation times: 1, 2, 3, 4, or 5 minutes. The irradiation procedure was
      performed twice. The flexural strength was determined using a testing machine MTS
      810 and measurements of Vickers hardness were made on Micromet 2100. The values
      were submitted to ANOVA and Tukey's test (P = .05). RESULTS: The K material
      showed a significant increase (P = .0010) in flexural strength following 5
      minutes of disinfection compared to control specimens. The flexural strength mean
      values of materials T, U, and N were not significantly affected (P > .05) by
      disinfection. Compared to the control group, the K material showed a significant
      increase in hardness (P < .001) following disinfection for 3, 4, and 5 minutes.
      For material U, disinfection for 4 and 5 minutes produced specimens with
      significantly increased hardness values (P < .001) compared to the control group.
      For material N, disinfection for 5 minutes resulted in significantly higher
      hardness values (P < .001) than the control group. CONCLUSION: Regardless of the
      irradiation time, the flexural strength and hardness of the materials evaluated
      were not detrimentally affected by microwave disinfection.

PMID- 19093061
TI  - The center of the incisive papilla for the selection of complete denture
      maxillary anterior teeth in 4 racial groups.
AB  - OBJECTIVES: To evaluate the use of the center of the incisive papilla as a guide
      for the selection of the proper width of maxillary dentures in 4 racial groups.
      METHOD AND MATERIALS: One hundred sixty stone casts were obtained from
      impressions of the maxillary arch of white, black, mixed, and Asian subjects. The
      occlusal surfaces of the casts were photocopied and the images placed on a
      digitizer. The most anterior and posterior points of the papilla and cusp tips of
      the canines were digitized. Dentofacial Planner Plus software was used to
      calculate the distance from a line passing through the cusp tips of the canines
      to the center of the papilla, defined as the midpoint of the anterior and
      posterior points of the papilla. The selection error (in millimeters) due to the
      clinical application of the method of the incisive papilla was calculated and
      analyzed. RESULTS: In all studied racial groups, there was no coincidence between
      the center of the incisive papilla and the canine line. The utilization of the
      center of the papilla would lead to the selection of wider artificial teeth. In
      24.9% of the white, 19.3% of the mixed, 32.9% of the black, and 15.5% of the
      Asian populations, errors greater than 4 mm would be present with the utilization
      of the papilla. CONCLUSION: The method of the center of the incisive papilla is
      not accurate, but may aid in initial artificial teeth selection for the racial
      groups studied.

PMID- 19093062
TI  - Dental caries experience in patients with aggressive periodontitis compared to
      those with chronic periodontitis.
AB  - OBJECTIVE: It has been reported that caries prevalence in patients with
      aggressive periodontitis (ie, juvenile periodontitis) might be higher than that
      in matched controls. However, the available results are inconclusive. The aim of
      this study was to assess this relationship by comparing caries experience among
      subjects with generalized aggressive periodontitis (AgP) and those with chronic
      periodontitis (CP) and to identify reasons for tooth loss in both groups. METHOD
      AND MATERIALS: A convenient sample of subjects with AgP (210) and CP (332) was
      evaluated for decayed, missing, and filled teeth (DMFT) by both clinical and
      radiographic methods. Statistical analysis was performed by t test and ANOVA.
      RESULTS: The AgP subjects have significantly less caries experience than the CP
      subjects older than 20 (P < .001). Tooth loss was mainly due to periodontal
      disease in AgP subjects and caries in CP subjects. CONCLUSION: Subjects with AgP
      have significantly less caries experience than subjects with CP over 20 years of
      age (P < .001).

PMID- 19093063
TI  - Evaluation of a 6% hydrogen peroxide tooth-whitening gel on enamel microhardness
      after extended use.
AB  - OBJECTIVES: To evaluate the effects of a 6% hydrogen peroxide tooth whitener,
      Xtra White, on sound human enamel microhardness in vitro after an extended and
      exaggerated simulated 8 weeks of product use. METHOD AND MATERIALS: Polished
      human enamel specimens were prepared and baseline microhardness and color
      measurements determined. The enamel specimens were exposed to a fluoride
      containing toothpaste for 30 seconds and then exposed to water, Xtra White, a
      control carbopol gel containing no hydrogen peroxide, or a carbonated beverage
      (each group, n = 8) for 20 minutes. Specimens were exposed to whole saliva at all
      other times. In order to simulate 8 weeks of extended product use, quadruple the
      length of the manufacturer's instructions, 112 treatments, were conducted.
      Microhardness measurements were taken after 2, 4, 6, and 8 weeks of simulated
      treatments, and color was measured after 2 and 8 weeks. RESULTS: The Xtra White
      treated specimens showed a statistically significant (P < .0001) increase in L*
      and decrease in b* compared to the water-treated specimens after 2 weeks
      simulated use, indicating bleaching had occurred. The carbonated beverage-treated
      specimens were significantly softened (P = .0009) compared to baseline after only
      1 treatment. The carbopol gel-treated specimens were significantly softened (P =
      .0028) after 2 weeks of simulated treatments compared to baseline. There were no
      statistically significant differences in enamel microhardness between baseline
      and all treatment times for XW and water groups. CONCLUSION: Xtra White does not
      have any deleterious effects on sound human enamel microhardness after an
      extended and exaggerated simulated 8 weeks of product use.

PMID- 19093064
TI  - Symptomatic urinary problems in female genital tract anomalies.
AB  - Most of urological abnormalities in urogenital anomalies are asymptomatic and
      need no special treatment; however, a few patients have critical urinary
      complaints and surgical corrections are required for them. Unfortunately, these
      coexisting urinary problems are often neglected and failed to be treated. So, it
      is necessary to delineate the diagnosis and treatment of similar anomalies. Eight
      typical patients who had urogenital anomalies with urinary discomfort in our
      institution were excerpted and reported. In this series, the urinary symptoms
      ranged from cyclical hematuria and urinary incontinence to infection symptom. The
      involved urological anatomies were generally categorized into three types:
      abnormal communication of urogenital tracts, malformation of bladder or ectopic
      ureter, and anomalies of urethral orifice. Surgical corrections were helpful for
      most cases. For patients with genitalia anomalies, the coexisting urological
      defects should be highlighted by our gynecologists, especially when they are
      symptomatic and require surgical correction.

PMID- 19093065
TI  - Association of adenylate cyclase 10 (ADCY10) polymorphisms and bone mineral
      density in healthy adults.
AB  - Phenotypic variation in bone mineral density (BMD) among healthy adults is
      influenced by both genetic and environmental factors. Sequence variations in the
      adenylate cyclase 10 (ADCY10) gene, which is also called soluble adenylate
      cyclase, have previously been associated with low spinal BMD in hypercalciuric
      patients. Since ADCY10 is located in the region linked to spinal BMD in our
      previous linkage analysis, we tested whether polymorphisms in this gene are also
      associated with normal BMD variation in healthy adults. Sixteen single-nucleotide
      polymorphisms (SNPs) distributed throughout ADCY10 were genotyped in two healthy
      groups of American whites: 1692 premenopausal women and 715 men. Statistical
      analyses were performed in the two groups to test for association between these
      SNPs and the femoral neck and lumbar spine areal BMD. We observed significant
      evidence of association (p < 0.01), with one SNP each in men and women. Genotypes
      at these SNPs accounted for <1% of hip BMD variation in men but 1.5% of spinal
      BMD in women. However, adjacent SNPs did not corroborate the association in
      either men or women. In conclusion, we found a modest association between an
      ADCY10 polymorphism and the spinal areal BMD in premenopausal white women.

PMID- 19093066
TI  - Comparison of quantitative cancellous bone connectivity analyses at two- and
      three-dimensional levels in dialysis patients.
AB  - Assessment of cancellous bone connectivity has the potential to aid in predicting
      fracture risk. Today, cancellous bone connectivity is generally assessed using
      bone sections obtained from biopsy. However, how reliably such two-dimensional (2
      D) analyses visualize the 3-D properties has not been evaluated. Biopsied iliac
      bone samples were obtained from 47 chronic hemodialysis patients. Bone samples
      were observed using a microfocus X-ray computed tomography (microCT) system en
      bloc, and the cancellous bone microstructure was quantitatively assessed at both
      the 2- and 3-D levels. Cancellous bone microarchitecture was successfully
      reconstructed from the data obtained by the microCT system. Most of the results
      from node-strut analysis (NSA) revealed no statistically significant correlations
      between the 2- and 3-D analyses, with the exception that the number of nodes
      (N.Nd/TV) showed a mild but significant correlation. In contrast, the marrow
      space star volumes (V*m) of the 2- and 3-D analyses were highly correlated. NSA
      parameters including N.Nd/TV showed significant correlations with V*m at the 3-D
      level. In conclusion, V*m values were similar in the 2- and 3-D analyses, while
      most of the 2-D NSA parameters did not reflect the 3-D ones. Since V*m and most
      of the NSA parameters were correlated in the 3-D analyses, 2-D NSA would seem to
      have serious limitations for the assessment of cancellous bone microstructural
      properties. Further studies will thus be needed to establish appropriate methods
      for assessing cancellous bone connectivity in clinical practice.

PMID- 19093067
TI  - Percutaneous biopsy of abdominal masses using 25-gauge needles.
AB  - PURPOSE: To evaluate the efficacy and safety of using 25-gauge needles to biopsy
      abdominal masses. MATERIAL AND METHODS: A 6-month period of using 25-gauge
      needles (study group) as the only needle (n = 98) or the initial needle (n = 24)
      to biopsy abdominal masses was analyzed retrospectively. Diagnostic rate,
      sensitivity, negative predictive value, complication rate, and number of passes
      were compared with the same parameters obtained during the preceding 6 months
      during which 117 abdominal masses were biopsied and 25-gauge needles were not
      used (control group). There were no significant differences in patient age,
      gender distribution, or difficulty ratio of biopsies (path length divided by mass
      diameter) between the groups. RESULTS: Diagnostic rates, sensitivities, and
      negative predictive values of biopsies in the study group (90.9% (111/122),
      91.8%, (89/97), and 63.6% (14/22), respectively), were not significantly
      different from those in the control group (91.5% (107/117), 97.8% (91/93), and
      87.5% (14/16), respectively). There were no major complications in either group;
      the complication rate in the control group (5.9%, 6/122) was not significantly
      different from the study group (4.9%, 7/117). Number of passes was significantly
      higher in the study group compared to the control group (mean values of 4.91 and
      4.44, respectively, P < 0.05). CONCLUSIONS: Abdominal masses can be biopsied with
      25-gauge needles, either alone or prior to larger needles, just as effectively
      and safely as with larger needles.

PMID- 19093068
TI  - Type A dissection after right coronary artery stent-implantation.

PMID- 19093069
TI  - Patterns of chemotherapy-induced hepatic injury and their implications for
      patients undergoing liver resection for colorectal liver metastases.
AB  - BACKGROUND AND AIMS: Neoadjuvant chemotherapy is increasingly being used to
      enlarge the cohort of patients who can be offered hepatic resection for
      malignancy. However, the impact of these agents on the liver parenchyma itself,
      and their effects on clinical outcomes following hepatic resection remain
      unclear. This review identifies patterns of regimen-specific chemotherapy-induced
      hepatic injury and assesses their impact on outcomes following hepatic resection
      for colorectal liver metastases (CLM). METHODS: An electronic search was
      performed using the MEDLINE (US Library of Congress) database from 1966 to May
      2007 to identify relevant articles related to chemotherapy-induced hepatic injury
      and subsequent outcome following hepatic resection. RESULTS: The use of the
      combination of 5-flourouracil and leucovorin is linked to the development of
      hepatic steatosis, and translates into increased postoperative infection rates. A
      form of non-alcoholic steatohepatitis (NASH) related to chemotherapy and
      otherwise known as chemotherapy-associated steatohepatitis (CASH) is closely
      linked to irinotecan-based therapy and is associated with inferior outcomes
      following hepatic surgery mainly due to hepatic insufficiency and poor
      regeneration. Data on sinusoidal obstruction syndrome (SOS) following treatment
      with oxaliplatin are less convincing, but there appears to be an increased risk
      for intra-operative bleeding and decreased hepatic reserve associated with the
      presence of SOS. Intra-arterial floxuridine therapy damages the extrahepatic
      biliary tree in addition to causing parenchymal liver damage, and has been shown
      to be associated with increased morbidity after hepatic resection. CONCLUSION:
      Agent-specific patterns of damage are now being recognized with increasing use of
      neoadjuvant chemotherapy prior to surgery. The potential benefits and risks of
      these should be considered on an individual patient basis prior to hepatic
      resection.

PMID- 19093070
TI  - Appraisal of immunomodulatory potential of Spirulina fusiformis: an in vivo and
      in vitro study.
AB  - In recent years, Spirulina has gained more and more attention from medical
      scientists as a nutraceutical and a source of potential pharmaceuticals. The
      present study was conducted to elucidate the immunomodulatory effect of Spirulina
      fusiformis (a cyanobacterium of the family Oscillatoriaceae) in vivo and in
      vitro. The in vivo effect of S. fusiformis (400 or 800 mg/kg body wt.) on humoral
      immune response, cell-mediated immune response and tumour necrosis factor alpha
      was investigated in mice. We also evaluated the effect of S. fusiformis (50 or
      100 microg/ml) in vitro on mitogen (phytohaemagglutinin)-induced T lymphocyte
      proliferation in heparinized human peripheral blood. For comparison,
      dexamethasone was used as a standard. In mice, S. fusiformis (400 or 800 mg/kg
      body wt.) administration significantly inhibited the humoral immune response,
      cell-mediated immune response (delayed-type hypersensitivity reaction (DTH)) and
      tumour necrosis factor alpha in a dose-dependent manner. In vitro, S. fusiformis
      (50 or 100 microg/ml) decreased the mitogen (phytohaemagglutinin)-induced T
      lymphocyte proliferation in a concentration-dependent manner when compared with
      control cells. These observations clearly suggest that S. fusiformis has a
      remarkable immunosuppressive effect, which provides a scientific validation for
      the popular use of this drug, and helped us in further work on investigating its
      complete mechanism of action.

PMID- 19093071
TI  - Gamma Knife surgery of large meningiomas: early response to treatment.
AB  - PURPOSE: Gamma Knife treatment is traditionally limited to tumours with a
      diameter not exceeding 3-3.5 cm. The current paper presents 97 patients with
      meningiomas with a minimum volume of 10 cm(3), treated with a prescription dose
      of 12 Gy (or sometimes less to protect neighbouring structures). The post
      treatment assessment of these patients, the early response to treatment and the
      complications of treatment are presented. METHODS: There were 97 patients, 70
      females and 27 males. The mean age was 48.1 years (range 20.4-87.2 years). The
      mean follow-up was 54 months (range 25-86 months). All tumours had a volume of 10
      cm(3) or more. The mean volume was 15.9 cm(3) (range 10.0-43.2 cm(3)). Post
      treatment follow-up used quantitative and qualitative assessments, which are
      described. RESULTS: No tumour continued to grow. Twenty-seven were smaller and 72
      unchanged in volume. Three patients suffered adverse radiation effects (defined
      as a new post-treatment oedema detected on the magnetic resonance image with or
      without contrast leakage). In one case this was silent. In two cases the clinical
      and radiological effects were temporary and resolved completely. CONCLUSIONS: It
      is suggested on the basis of this material that the dosimetry used here permits
      the safe Gamma Knife treatment of larger meningiomas within the range reported.
      The early radiological response is encouraging, but further follow-up is needed
      to check long term tumour control. A qualitative method of tumour volume
      assessment is presented. It seems to be a simpler and more reliable way of
      assessing tumour volume changes than other methods currently in routine use.

PMID- 19093072
TI  - Deep brain stimulation of the posterior subthalamic area in the treatment of
      tremor.
AB  - BACKGROUND: Several studies have described lesional therapy in the posterior
      subthalamic area (PSA) in the treatment of various movement disorders. Recently,
      some publications have illustrated the effect of deep brain stimulation (DBS) in
      this area in patients with Parkinson's disease, essential tremor, MS-tremor, and
      other forms of tremor. Even though the clinical series is small, the reported
      benefits prompted us to explore DBS in this area in the treatment of tremor.
      METHOD: Five patients with tremor were operated using unilateral DBS of the PSA.
      Two patients had dystonic tremor, one primary writing tremor, one cerebellar
      tremor and the other neuropathic tremor. All patients were assessed before and 1
      year after surgery using items 5 and 6 (tremor of the upper extremity), 11-14
      (hand function), and when appropriate item 10 (handwriting) from the essential
      tremor rating scale. FINDINGS: The mean improvement on stimulation after 1 year
      was 87%. A pronounced and sustained microlesional effect was seen in several of
      the patients, and while the mean improvement off stimulation was 56% the
      reduction in the three patients with the most pronounced effect was 89%. The two
      patients with dystonic tremor did also become free of the dystonic symptoms and
      pain in the treated arm. No severe complication occurred. CONCLUSIONS: DBS of the
      PSA in this small group of patients had an excellent effect on the different
      forms of tremor, except for the neuropathic tremor where the effect was moderate.
      These preliminary results suggest PSA to be an effective target for the treatment
      of various forms of tremor. Further studies concerning indications, safety and
      efficacy of DBS in the posterior subthalamic area are required.

PMID- 19093073
TI  - New policies to consolidate the journal's hold on its latest position.

PMID- 19093074
TI  - A rare case of vomiting: fourth ventricular B-cell lymphoma.
AB  - We document the case of a 69-year-old man presenting with 6 weeks of intractable
      vomiting. Magnetic Resonance Imaging showed a homogenously enhancing mass in the
      caudal fourth ventricle. Surgical exploration and biopsy was performed and
      pathological examination demonstrated a high-grade B-cell lymphoma. The lesion
      was a primary tumour in an immuno-competent patient. Despite the increasing
      incidence of primary central nervous system lymphomas this is believed to be only
      the third ever case to have occurred at this rare site. We suggest that primary B
      cell lymphoma should be considered with homogenous lesions of the fourth
      ventricle.

PMID- 19093076
TI  - Selenium deficiency as a possible contributor of goiter in schoolchildren of
      Isfahan, Iran.
AB  - The prevalence of goiter still remains high in some areas of Iran in spite of
      iodine supplementation. In the present study, we investigated the role of
      selenium (Se) deficiency in the etiology of goiter in Isfahan. Two thousand three
      hundred thirty-one schoolchildren were selected by multistage random sampling.
      Thyroid size was estimated in each child by inspection and palpation. Urinary
      iodine concentration (UIC) and plasma Se were measured. Overall, 32.9% of the
      2,331 children had goiter. The median UIC was 19.55 microg/dl. Plasma Se was
      measured in 96 goitrous and 72 nongoitrous children. The mean +/- SD of plasma Se
      in goitrous and nongoitrous children was 66.86 +/- 21.82 and 76.67 +/- 23.33
      microg/l, respectively (P = 0.006). Goitrous girls had lower plasma Se level than
      nongoitrous girls (65.62 +/- 21.64 vs. 76.51 +/- 22.61 microg/dl, P = 0.02).
      Goitrous boys had lower plasma Se level than nongoitrous boys (68.45 +/- 22.21
      vs. 76.91 +/- 24.76 microg/l, P = 0.14). The prevalence of Se deficiency was
      significantly higher in goitrous boys and girls than nongoitrous children. Se
      deficiency is among the contributors of goiter in Isfahan goitrous
      schoolchildren. However, the role of other micronutrient deficiencies or
      goitrogens should be investigated in this region.

PMID- 19093075
TI  - Heme-dependent metalloregulation by the iron response regulator (Irr) protein in
      Rhizobium and other Alpha-proteobacteria.
AB  - Perception and response to nutritional iron by bacteria is essential for
      viability, and for the ability to adapt to the environment. The iron response
      regulator (Irr) is part of a novel regulatory scheme employed by Rhizobium and
      other Alpha-Proteobacteria to control iron-dependent gene expression.
      Bradyrhizobium japonicum senses iron through the status of heme biosynthesis to
      regulate gene expression, thus it responds to an iron-dependent process rather
      than to iron directly. Irr mediates this response by interacting directly with
      ferrochelatase, the enzyme that catalyzes the final step in heme biosynthesis.
      Irr is expressed under iron limitation to both positively and negatively modulate
      gene expression, but degrades in response to direct binding to heme in iron
      sufficient cells. Studies with Rhizobium reveal that the regulation of iron
      homeostasis in bacteria is more diverse than has been generally assumed.

PMID- 19093077
TI  - Influence of drinking and/or cooking with Jinzu River water on the development of
      Itai-itai disease.
AB  - This study was undertaken to estimate the amount of cadmium (Cd) exposure needed
      for the development of Itai-itai disease and the influence of using Jinzu River
      water for drinking and/or cooking on its development. The subjects comprised 38
      Itai-itai disease patients admitted both for questionnaire survey and medical
      testing. The period when the patients started to perceive leg/back pain was
      defined as 'mild disease onset' and that when they experienced the most severe
      manifestations such as ambulatory disturbance as 'severe disease onset'. In a
      comparison of non-users/users of river water, mean age and lifetime Cd intake
      (LCd) estimated from the daily consumption of rice and other foods at the onset
      of mild or severe disease showed smaller values in the users than non-users. LCd
      in non-users/users of river water for drinking and/or cooking were estimated as
      3.46-3.60 g/2.58-2.63 g at mild disease onset and 4.24-4.44 g/3.50-3.54 g at
      severe disease onset. A portion of the differences in LCd in non-users/users is
      attributable to the influence of Cd consumption from the use of river water,
      although it was suggested that LCd estimated from eating Cd-polluted rice exerted
      a greater influence on the development of Itai-itai disease than drinking and/or
      cooking with Cd-polluted river water.

PMID- 19093078
TI  - PII, the key regulator of nitrogen metabolism in the cyanobacteria.
AB  - PII proteins are a protein family important to signal transduction in bacteria
      and plants. PII plays a critical role in regulation of carbon and nitrogen
      metabolism in cyanobacteria. Through conformation change and covalent
      modification, which are regulated by 2-oxoglutarate, PII interacts with different
      target proteins in response to changes of cellular energy status and carbon and
      nitrogen sources in cyanobacteria and regulates cellular metabolism. This article
      reports recent progress in PII research in cyanobacteria and discusses the
      mechanism of PII regulation of cellular metabolism.

PMID- 19093079
TI  - Characterization of a sodium-regulated glutaminase from cyanobacterium
      Synechocystis sp. PCC 6803.
AB  - Glutaminase is widely distributed among microorganisms and mammals with important
      functions. Little is known regarding the biochemical properties and functions of
      the deamidating enzyme glutaminase in cyanobacteria. In this study a putative
      glutaminase encoded by gene slr2079 in Synechocystis sp. PCC 6803 was
      investigated. The slr2079 was expressed as histidine-tagged fusion protein in
      Escherichia coli. The purified protein possessed glutaminase activity, validating
      the functional assignment of the genomic annotation. The apparent K (m) value of
      the recombinant protein for glutamine was 26.6 +/- 0.9 mmol/L, which was
      comparable to that for some of other microbial glutaminases. Analysis of the
      purified protein revealed a two-fold increase in catalytic activity in the
      presence of 1 mol/L Na(+). Moreover, the K (m) value was decreased to 12.2 +/-
      1.9 mmol/L in the presence of Na(+). These data demonstrate that the recombinant
      protein Slr2079 is a glutaminase which is regulated by Na(+) through increasing
      its affinity for substrate glutamine. The slr2079 gene was successfully disrupted
      in Synechocystis by targeted mutagenesis and the Deltaslr2079 mutant strain was
      analyzed. No differences in cell growth and oxygen evolution rate were observed
      between Deltaslr2079 and the wild type under standard growth conditions,
      demonstrating slr2079 is not essential in Synechocystis. Under high salt stress
      condition, however, Deltaslr2079 cells grew 1.25-fold faster than wild-type
      cells. Moreover, the photosynthetic oxygen evolution rate of Deltaslr2079 cells
      was higher than that of the wild-type. To further characterize this phenotype, a
      number of salt stress-related genes were analyzed by semi-quantitative RT-PCR.
      Expression of gdhB and prc was enhanced and expression of desD and guaA was
      repressed in Deltaslr2079 compared to the wild type. In addition, expression of
      two key enzymes of ammonium assimilation in cyanobacteria, glutamine synthetase
      (GS) and glutamate synthase (GOGAT) was examined by semi-quantitative RT-PCR.
      Expression of GOGAT was enhanced in Deltaslr2079 compared to the wild type while
      GS expression was unchanged. The results indicate that slr2079 functions in the
      salt stress response by regulating the expression of salt stress related genes
      and might not play a major role in glutamine breakdown in Synechocystis.

PMID- 19093080
TI  - Expression and function analysis of the metallothionein-like (MT-like) gene from
      Festuca rubra in Chlamydomonas reinhardtii chloroplast.
AB  - The cDNA of the metallothionein-like (MT-like) gene from Festuca rubra cv. Merlin
      was optimized with bias codon of Chlamydomonas reinhardtii chloroplast genome.
      The optimized MT-like gene was delivered into C. reinhardtii chloroplast and the
      transgenic strains expressing MT-like gene was obtained. PCR-Southern blot and RT
      PCR-Southern blot analysis demonstrated that the MT-like gene was integrated into
      chloroplast genome of C. reinhardtii and expressed at the transcriptional level.
      The cadmium binding capacity of the transgenic C. reinhardtii was determined by
      hydride generation-atomic fluorescence spectrometry (HG-AFS) and the binding
      properties were analyzed. Results showed that the transgenic C. reinhardtii
      expressing the MT-like gene exhibited remarkably higher Cd(2+) binding capacity
      and grew to higher densities at toxic Cd(2+) concentrations (40-100 micromol/L)
      than the wild type strain, and that the IC(50) of Cd(2+) (3-d treating) to algal
      cell growth of transgenic strain was 55.43% higher than that of the wild type
      strain, indicating that the Cd(2+) binding capacity and Cd(2+) tolerance of C.
      reinhardtii was enhanced through the expression of the foreign MT-like gene in
      chloroplast.

PMID- 19093081
TI  - The response of electron transport mediated by active NADPH dehydrogenase
      complexes to heat stress in the cyanobacterium Synechocystis 6803.
AB  - The electron-transport machinery in photosynthetic membranes is known to be very
      sensitive to heat. In this study, the rate of electron transport (ETR) driven by
      photosystem I (PSI) and photosystem II (PSII) during heat stress in the wild-type
      Synechocystis sp. strain PCC 6803 (WT) and its ndh gene inactivation mutants
      DeltandhB (M55) and DeltandhD1/ndhD2 (D1/D2) was simultaneously assessed by using
      the novel Dual-PAM-100 measuring system. The rate of electron transport driven by
      the photosystems (ETR(PSs)) in the WT, M55, and D1/D2 cells incubated at 30
      degrees C and at 55 degrees C for 10 min was compared. Incubation at 55 degrees C
      for 10 min significantly inhibited PSII-driven ETR (ETR(PSII)) in the WT, M55 and
      D1/D2 cells, and the extent of inhibition in both the M55 and D1/D2 cells was
      greater than that in the WT cells. Further, PSI-driven ETR (ETR(PSI)) was
      stimulated in both the WT and D1/D2 cells, and this rate was increased to a
      greater extent in the D1/D2 than in the WT cells. However, ETR(PSI) was
      considerably inhibited in the M55 cells. Analysis of the effect of heat stress on
      ETR(PSs) with regard to the alterations in the 2 active NDH-1 complexes in the
      WT, M55, and D1/D2 cells indicated that the active NDH-1 supercomplex and
      mediumcomplex are essential for alleviating the heat-induced inhibition of
      ETR(PSII) and for accelerating the heat-induced stimulation of ETR(PSI),
      respectively. Further, it is believed that these effects are most likely brought
      about by the electron transport mediated by each of these 2 active NDH-1
      complexes.

PMID- 19093082
TI  - Enhanced production of lutein in heterotrophic Chlorella protothecoides by
      oxidative stress.
AB  - The fast growing unicellular green microalgae Chlorella protothecoides has
      attracted interest as a promising organism for commercial production of a high
      value carotenoid, lutein, by heterotrophic fermentation. Effects of two oxidant
      forming reactive oxygen species (ROS) on the biomass concentration, and yield and
      content of lutein in batch culture of heterotrophic Chlorella protothecoides were
      investigated in this study. The addition of 0.1 mmol/L H(2)O(2) and 0.01 mmol/L
      NaClO plus 0.5 mmol/L Fe(2+) to the culture led to the generation of (.)OH and
      enhanced the lutein content from 1.75 to 1.90 and 1.95 mg/g, respectively. The
      lutein content further increased to 1.98 mg/g when 0.01 mmol/L H(2)O(2) and 0.5
      mmol/L NaClO were added to generate (1)O(2). The maximum yield of lutein (28.5,
      29.8 and 31.4 mg/L) and a high biomass concentration (15.0, 15.3 and 15.9 g/L)
      were also achieved through the above treatments. The results indicated that 1O2
      could promote lutein formation and enhance lutein production in heterotrophic
      Chlorella protothecoides. Moreover, (1)O(2) produced from the reaction of
      H(2)O(2) and NaClO was more effective in enhancing lutein production and reducing
      biomass loss than (.)OH from the reaction of H(2)O(2) or NaClO plus Fe(2+).

PMID- 19093083
TI  - The synthesis of astaxanthin esters, independent of the formation of cysts,
      highly correlates with the synthesis of fatty acids in Haematococcus pluvialis.
AB  - The compositions and contents of astaxanthin esters and fatty acids in four types
      of Haematococcus pluvialis cells were studied by HPLC and GC-MS. Results showed
      that the synthesis and accumulation of astaxanthin was independent of the
      formation of cysts, but was highly correlated with the synthesis and accumulation
      of fatty acids, though it is an well known phenomenon that the accumulation of
      astaxanthin is usually accompanied by the formation of cyst. The red cysts
      contain more than 30% of fatty acids, with 81% of the unsaturated fatty acids.
      Taken together, besides a resource of astaxanthin, H. pluvialis would be a good
      resource of valuable fatty acids.

PMID- 19093084
TI  - Precise identification of photosynthetic glycerolipids in microalga Tetraselmis
      chuii by UPLC-ESI-Q-TOF-MS.
AB  - Precise structural identification of photosynthetic polar glycerolipids in
      microalga Tetraselmis chuii has been established using Ultra Performance Liquid
      Chromatography-Electrospray ionization-Quadrupole-Time of Flight Mass
      Spectrometry (UPLC-ESI-Q-TOF-MS) by direct analysis of the total lipids extract.
      The mass spectrometry was performed in reflective time-of-flight using electron
      spraying ionization in both positive and negative modes. The structural
      determination was based on the characteristic product ions yielded by different
      glycerolipids under ESI-MS/MS mode, and confirmed the molecular species by the
      carboxylate anions produced by glycerolipids in the negative mode. As a result,
      more than 40 lipid molecular species, including 11 monogalactosyldiacylglycerols
      (MGDG), 7 digalactosyldiacylglycerols (DGDG), 16 sulfoquinovosyldiacylglycerols
      (SQDG), and 9 phosphatidylglycerols (PG), were detected in Tetraselmis chuii,
      which had never been identified before in this microalga. Furthermore, some
      intact lipid molecules with hydroxylated fatty acids that could not be detected
      by the traditional GC-MS method were found this time, providing novel information
      for the photosynthetic lipidome of Tetraselmis chuii. Comparative studies on
      fatty acids at the sn-2 position showed that SQDG and MGDG are dominantly
      biosynthesized through the prokaryotic pathway, PG is a typically mixed
      biosynthetic pathway, while DGDG is somewhat peculiar with C14:0 and C16:0 at its
      sn-2 position. This method could provide a full structural profile of intact
      photosynthetic lipid molecular species, which may be applied to study the
      physiological and ecological functions of lipid by monitoring their individual
      changes.

PMID- 19093085
TI  - Comparative analysis of astaxanthin and its esters in the mutant E1 of
      Haematococcus pluvialis and other green algae by HPLC with a C30 column.
AB  - A gradient reversed-phase high-performance liquid chromatography (HPLC) method
      using a C30 column was developed for the simultaneous determination of
      astaxanthin, astaxanthin monoesters and astaxanthin diesters in the green algae
      Chlorococcum sp., Chlorella zofingiensis, Haematococcus pluvialis and the mutant
      E1, which was obtained from the mutagenesis of H. pluvialis by exposure to UV
      irradiation and ethyl methanesulphonate (EMS) with subsequent screening using
      nicotine. The results showed that the contents of total astaxanthins including
      free astaxanthin and astaxanthin esters ranged from 1.4 to 30.9 mg/g dry biomass
      in these green algae. The lower total astaxanthin levels (< 2 mg/g dry biomass)
      were detected in the green algae Chlorococcum sp. and C. zofingiensis. The higher
      total astaxanthin levels (>16 mg/g dry biomass) were found in the green alga H.
      pluvialis and its mutant E1. It is notable that the mutant E1 is found to have
      considerably higher amounts of total astaxanthin (30.9 mg/g) as compared to the
      wild strain of H. pluvialis (16.1 mg/g). This indicates that UV-irradiation and
      EMS compound mutagenesis with subsequent screening using nicotine is an effective
      method for breeding of a high-producing astaxanthin strain of H. pluvialis. In
      addition, the green alga C. zofingiensis had a remarkably higher percentage of
      astaxanthin diesters (76.3% of total astaxanthins) and a remarkably lower
      percentage of astaxanthin monoesters (18.0% of total astaxanthins) in comparison
      with H. pluvialis (35.5% for diesters and 60.9% for monoesters), the mutant E1
      (49.1% and 48.1%) and Chlorococcum sp. (18.0% and 58.6%).

PMID- 19093086
TI  - Recombinant expression of rt-PA gene (encoding Reteplase) in gametophytes of the
      seaweed Laminaria japonica (Laminariales, Phaeophyta).
AB  - The life cycle of seaweed Laminaria japonica involves a generation alternation
      between diploid sporophyte and haploid gametophte. The expression of foreign
      genes in sporophte has been proved. In this research, the recombinant expression
      in gametophyte was investigated by particle bombardment with the rt-PA gene
      encoding the recombinant human tissue-type plasminogen activator (Reteplase),
      which is a thrombolytic agent for acute myocardial infarction (AMI). Transgenic
      gametophytes were selected by their resistance to herbicide phosphiothricin
      (PPT), and proliferated in an established bubble column photo-bioreactor.
      According to the results from quantitative ELISA, Southern blotting, and fibrin
      agarose plate assay (FAPA) for bioactivity, it was showed that the rt-PA gene had
      been integrated into the genome of gametophytes of L. japonica, and the
      expression product showed the expected bioactivity, implying the proper post
      transcript modification in haploid gametophyte.

PMID- 19093087
TI  - The spatial and temporal distribution of microalgae in the South China Sea:
      evidence from GIS-based analysis of 18S rDNA sequences.
AB  - The purpose of this study was to estimate the spatial and temporal variation of
      microalgae in the South China Sea and to demonstrate the environmental factors
      controlling the diversity of microalgae by GIS (geographic information system)
      based analysis of 18S rDNA sequences. Six 18S rDNA libraries were constructed
      from environmental samples collected at different sites in the study area, and
      more than 600 18S rDNA sequences were determined. The rDNA sequence data were
      then analyzed by DIVA-GIS software to display the spatial and temporal variation
      of phytoplankton's composition. It was shown that the autotrophic eukaryotic
      plankton dominated over the heterotrophic cells in most of our clone libraries,
      and the dominating phytoplankton was Dinophyceae except for Bacillariophyta at
      the Xiamen harbor. The percentages of these two groups were controlled by water
      temperature and salinity. Our results also revealed that the species composition
      of Chlorophyta showed a close relationship with latitude, changing from
      Prasinophyceae at the high latitude to Trebouxiophyceae at the low latitude.
      Several newly classified picoplankton lineages were first uncovered in the South
      China Sea, including the pico-sized green alga Ostreococcus sp. and Picochlorum
      eukaryotum, and picobiliphytes, which was just discovered in 2007 with unknown
      affinities to other eukaryotes. Their spatial and temporal variation were also
      analyzed and discussed.

PMID- 19093088
TI  - The response of the early developmental stages of Laminaria japonica to enhanced
      ultraviolet-B radiation.
AB  - The responses of the early development of Laminaria japonica collected from
      Kiaochow Bay in China to enhanced ultraviolet-B radiation (UV-B, 280-320 nm) were
      studied in the laboratory. The low UV-B radiations (11.7-23.4 J x m(-2) x d(-1))
      had no significant effects on zoospores attachment, but when the UV-B dose > 35.1
      J x m(-2) x d(-1) the attachment decreased significantly compared with the
      control. Germination of embryospores was >93% under the low (11.7-35.1 J x m(-2)
      x d(-1)) doses, and in the range of 78.5%-88.5% under the high (46.8-70.2 J x m(
      2) x d(-1)) UV-B doses, indicating a significant radiation effect. Under the
      higher UV-B exposure (35.1-70.2 J x m(-2) x d(-1)), all of the few gametophytes
      formed from embryospores died 120 h post-release. After exposure to the low UV-B
      radiation (11.7-23.4 J x m(-2) x d(-1)), the formation of sporophytes decreased
      and the female gametophyte clones increased compared with the control. However,
      the sex ratio and the relative growth of female gametophytes/sporophytes had not
      significantly changed. According to the results, enhanced UV-B radiation has a
      significant effect on the early development of L. japonica under laboratory
      conditions, suggesting that the UV-B radiation could not be overlooked as one of
      the important environmental factors influencing the ontogeny of macroalgae living
      in marine ecosystems.

PMID- 19093089
TI  - Structure of reproductive apparatus of Gracilaria/Gracilariopsis lemaneiformis
      (Gracilariaceae, Rhodophyta).
AB  - Reproductive apparatus of Gracilaria/Gracilariopsis lemaneiformis collected from
      Qingdao city were studied with a light and a transmission electron microscope.
      The special superficial arrangement of spermatangium for this species was clearly
      observed, and the ultrastructure of spermatangial development revealed the
      similar cytodynamic pattern followed by all the Gracilariaceae members developed
      from spermatangial mother cells to spermatangium. The female reproductive
      apparatus before fertilization was also observed and trichogyne was found
      protruding above the cortex, contrary to the earlier reports. Tetrasporangium was
      formed by an outer cortical cell and the tetraspores became spherical and
      expended after being released.

PMID- 19093090
TI  - Impacts of increased atmospheric CO2 concentration on photosynthesis and growth
      of micro- and macro-algae.
AB  - Marine photosynthesis drives the oceanic biological CO(2) pump to absorb CO(2)
      from the atmosphere, which sinks more than one third of the industry-originated
      CO(2) into the ocean. The increasing atmospheric CO(2) and subsequent rise of
      pCO(2) in seawater, which alters the carbonate system and related chemical
      reactions and results in lower pH and higher HCO(3) (-) concentration, affect
      photosynthetic CO(2) fixation processes of phytoplanktonic and macroalgal species
      in direct and/or indirect ways. Although many unicellular and multicellular
      species can operate CO(2)-concentrating mechanisms (CCMs) to utilize the large
      HCO(3) (-) pool in seawater, enriched CO(2) up to several times the present
      atmospheric level has been shown to enhance photosynthesis and growth of both
      phytoplanktonic and macro-species that have less capacity of CCMs. Even for
      species that operate active CCMs and those whose photosynthesis is not limited by
      CO(2) in seawater, increased CO(2) levels can down-regulate their CCMs and
      therefore enhance their growth under light-limiting conditions (at higher CO(2)
      levels, less light energy is required to drive CCM). Altered physiological
      performances under high-CO(2) conditions may cause genetic alteration in view of
      adaptation over long time scale. Marine algae may adapt to a high CO(2) oceanic
      environment so that the evolved communities in future are likely to be
      genetically different from the contemporary communities. However, most of the
      previous studies have been carried out under indoor conditions without
      considering the acidifying effects on seawater by increased CO(2) and other
      interacting environmental factors, and little has been documented so far to
      explain how physiology of marine primary producers performs in a high-CO(2) and
      low-pH ocean.

PMID- 19093092
TI  - [Bufexamac-induced pigmented purpuric eruption].
AB  - We report on a case of a bufexamac-induced allergic contact dermatitis with
      hematogenous dissemination presenting with the clinical and histological picture
      of a pigmented purpuric eruption. To our knowledge this is the first report on a
      bufexamac-induced pigmented purpuric dermatosis. It represents a further example
      of the clinical variety of cutaneous side-effects caused by bufexamac.

PMID- 19093093
TI  - [Audiometric thresholds estimated by auditory steady-state responses. Influence
      of EEG amplitude and test duration on accuracy].
AB  - OBJECTIVE: To examine the influence of electroencephalogram (EEG) amplitude, test
      duration, and residual noise on the definition of threshold criteria for auditory
      steady-state responses (ASSR) in three representative populations. METHODS: EEG
      recordings from 61 patients, 11 sedated babies, and 53 relaxed volunteers were
      used in an offline analysis that calculated the mean EEG amplitude and the time
      course of residual noise. Additionally, the time course of residual noise and the
      test duration for a fixed level of residual noise were estimated from the mean
      EEG amplitude using the "square root of N" law of averaging. RESULTS: A strong
      correlation between measured and predicted residual noise was found in all three
      groups. The mean EEG amplitude as well as the predicted test duration for a fixed
      residual noise level differed significantly among the three groups, with EEG
      amplitudes in clinical patients being four times greater than in relaxed
      volunteers. CONCLUSIONS: The strong correlation between EEG amplitude, test
      duration, and residual noise in ASSR recordings allows for the prediction of
      individual test duration or residual noise levels in advanced testing algorithms.
      This study found that high mean EEG amplitudes in awake patients considerably
      reduce the accuracy of hearing thresholds estimated by ASSR.

PMID- 19093094
TI  - [Lymph node surgery in urological tumors].

PMID- 19093095
TI  - [Posterior operative correction of idiopathic scoliosis. Value of pedicle screws
      versus hooks].
AB  - Posterior correction and fusion of scoliosis with multisegmental instrumentation
      systems was developed by Cotrel-Dubousset in the 1980s. Initially correction and
      instrumentation was performed using hooks only. Later pedicle screws were
      implemented first for the lumbar and then for the thoracic spine. Nowadays
      instrumentation based on pedicle screws only is well established for posterior
      scoliosis surgery. Biomechanical studies demonstrated higher pull-out forces for
      pedicle than for hook constructs.In clinical studies several authors reported
      better Cobb angle correction of the primary and the secondary curves and less
      loss of correction in pedicle screw versus hook instrumentations. Furthermore,
      pedicle screw instrumentation allows fewer segments to be fused, especially
      caudally, and thus saving mobile segments. In most of these publications there
      were no differences in operation time, blood loss and complication rates. In
      summary, there is better curve correction without an increased risk using
      multisegmental pedicle screw instrumentation in modern posterior scoliosis
      surgery.

PMID- 19093097
TI  - [Scoliosis surgery in children from the viewpoint of anaesthesiology].
AB  - Anaesthesia for scoliosis surgery in children is a challenge for the paediatric
      anaesthesiologist. The large range of underlying pathologies causing deranged
      physiology in an inhomogeneous patient group ranging from neonates to adolescents
      necessitates diligent and individual preparation for each case. Due to the
      invasiveness of the operation demanding anaesthetic care is necessary. This
      review highlights current approaches to monitoring, anaesthetic regimen,
      positioning of the patient, blood conservation and transfusion, age-related
      pathophysiology, ventilation and postoperative pain therapy. The introduction of
      neurophysiologic spinal cord monitoring requires certain adaptations of the
      anaesthetic regimen to suit technological advances.

PMID- 19093096
TI  - [Bone substitutes in scoliosis surgery].
AB  - In spinal fusion procedures, the local bone that is resected serves as the base
      bone graft for attaining biological fusion. The local bone is frequently not
      sufficient and requires supplementary grafting. Autologous bone transplantation
      is still regarded as the gold standard but might cause additional complications;
      also, autograft resources are limited. Alternatively, allografts and a wide
      variety of different bone substitutes are available.The bone substitutes
      currently used in scoliosis surgery are presented, and their clinical
      significance is elucidated by a review of the literature. Furthermore, our own
      experiences and clinical practice are compared with those in the literature and
      are critically discussed. The recently growing number of scientific publications
      reporting on bone substitutes reflects the immense interest and relevance of this
      issue. In scoliosis surgery, calcium phosphate ceramics together with bone marrow
      aspirate are increasingly applied.Although harvesting of autologous bone
      continues to be the accepted standard to extend the local autograft in scoliosis
      surgery, there is a clear trend toward the use of bone substitutes.

PMID- 19093098
TI  - [Arthroscopic versus open anterior shoulder stabilization. A systematic
      validation].
AB  - The treatment of traumatic anterior glenohumeral instability has been a topic of
      debate over the last couple of decades. However, a consensus exists regarding the
      necessity of an individualized treatment plan based on the type and degree of
      instability and the patient's functional demands. Various open and arthroscopic
      techniques are among the currently used surgical procedures. Open reconstruction
      of the capsulolabral complex had been considered the treatment of choice for many
      years, but the latest results for arthroscopic anterior shoulder stabilization
      demonstrate its increasing use. The current literature suggests that with the
      introduction of suture anchors, it is possible to mirror the principles of open
      anterior shoulder stabilization and thus combine the general advantages of
      arthroscopic surgery with a low recurrence rate.

PMID- 19093099
TI  - [Classification and diagnostics of unstable shoulders].
AB  - Shoulder instability includes a vast spectrum of different manifestations ranging
      from painful hyperlaxity to chronic locked shoulder dislocations. A correct
      diagnosis and classification is essential to establish an adequate treatment
      strategy. The correct use of different clinical tests and signs in combination
      with the corresponding imaging diagnostics allows an explicit classification and
      therefore the correct choice of treatment regimes in the majority of cases.

PMID- 19093100
TI  - [Update on shoulder instability].

PMID- 19093102
TI  - Optical sensing in medicine.

PMID- 19093103
TI  - Colourimetric characterisation of disposable optical sensors from
      spectroradiometric measurements.
AB  - Spectroradiometric measurements of reflectance and CIELAB hue-angle, were tested
      for K(I) determination using disposable optical sensors based on ion exchange
      mechanism. The linearisation of the sigmoidal response function, using a logistic
      regression, increases the linear range noticeably to 7.65 x 10(-8)-1.5 M and 1.22
      x 10(-7)-1.5 M for CIELAB hue-angle and reflectance, respectively. The trueness
      of both procedures was demonstrated comparing it with results obtained by a DAD
      spectrophotometer used as a reference measurement procedure. The usefulness of
      the procedure was checked by analysing K(I) in different types of waters and
      beverages. Additionally, we studied the possible visual discrimination for the
      whole potassium range tested, obtaining the possibility of discriminating twelve
      groups of concentrations.

PMID- 19093101
TI  - Evidence for mediation of nociception by injection of the NK-3 receptor agonist,
      senktide, into the dorsal periaqueductal gray of rats.
AB  - RATIONALE: Ultrasound vocalizations (USVs) at approximately 22 kHz are usual
      components of the defensive response of rats. However, depending on the neural
      substrate that is activated, such as the dorsal periaqueductal gray (dPAG), USV
      emissions may be reduced. Activation of neurokinin-1 (NK-1)-mediated mechanisms
      of the dPAG causes analgesia, reduced 22 kHz USVs, and anxiogenic-like effects in
      rats exposed to the elevated plus maze (EPM). Involvement of other types of
      neurokinin receptors in this activation has not yet been evaluated. OBJECTIVES:
      The present study examined whether local injections of the selective NK-3 agonist
      senktide (1-100 pmol/0.2 microL) into the dPAG can (1) cause anxiogenic effects
      in the EPM, (2) influence novelty-induced 22 kHz USVs, or (3) change nociceptive
      reactivity in the tail-flick test. RESULTS: Senktide elicited a significant
      increase in exploratory behavior, an effect accompanied by hyperalgesia and an
      increase in the number of 22 kHz USVs. The nociceptive effects, increased
      locomotor activity, and USV emissions elicited by local injections of senktide
      (50 pmol/0.2 microL) were reduced by prior injections of the selective NK-3
      receptor antagonist SB222200 (50 pmol/0.2 microL) into the dPAG. CONCLUSIONS:
      These findings show that NK-3 receptors in the dPAG mediate nociceptive responses
      in this area, contrasting with the known fear-related processes mediated by NK-1
      receptors in the dPAG. Both hyperalgesia and fear-related processes are
      accompanied by emissions of 22 kHz USVs.

PMID- 19093104
TI  - Bimanual 1:1 with 90 degrees continuous relative phase: difficult or easy!
AB  - The purpose of the present experiment was to observe the performance of
      participants attempting to produce a 1:1 bimanual coordination pattern with 90
      degrees relative phase between the arms when feedback concerning the movement of
      the two limbs was integrated within a Lissajous plot and when this information
      was withdrawn. One group was paced with an auditory metronome and the other was
      encouraged to increase frequency when they fell below the goal frequency. We
      predicted that providing a salient integrated feedback display without a
      metronome would allow participants to effectively tune-in the goal relative phase
      pattern within several minutes; instead of several days as typically found in the
      literature when the metronome was used. The data indicated remarkably effective
      performances after 5 min of practice when the metronome was not used, with motion
      of both limbs harmonic in nature, and continuous relative phase errors
      (approximately 10 degrees) and standard deviation of continuous relative phase
      (approximately 10 degrees) relatively small. This seems remarkable given that
      this coordination pattern has proven relatively difficult to perform under normal
      and Lissajous feedback conditions even after several days of practice. As
      predicted relative phase errors and variability increased substantially when the
      metronome was used. When the extrinsic feedback was withdrawn all participants
      tended to drift from the required 90 degrees relative phase, but the cycle
      duration variability in the two limbs remained stable and limb motion remained
      harmonic in nature. The current findings suggest that some of the difficulty
      typically associated with producing various relative phase patterns is due to the
      less than optimal perceptual information available in the various testing
      situations and the use of pacing metronomes.

PMID- 19093106
TI  - Intravascular papillary endothelial hyperplasia of the calf in an infant: MR
      features with histological correlation.
AB  - Intravascular papillary endothelial hyperplasia (IPEH), also known as Masson
      tumour, is a rare nonneoplastic vascular lesion caused by the abnormal
      proliferation of endothelial cells. IPEH presenting as a soft-tissue mass may
      simulate a sarcomatous tumour clinically and radiographically. We report an
      infant with IPEH affecting the right calf. The MRI appearance is described, and
      the literature is briefly reviewed. Knowledge of the MR characteristics of IPEH
      may facilitate its diagnosis and obviate an invasive procedure.

PMID- 19093105
TI  - Integration of auditory and visual information in the recognition of realistic
      objects.
AB  - Recognizing a natural object requires one to pool information from various
      sensory modalities, and to ignore information from competing objects. That the
      same semantic knowledge can be accessed through different modalities makes it
      possible to explore the retrieval of supramodal object concepts. Here, object
      recognition processes were investigated by manipulating the relationships between
      sensory modalities, specifically, semantic content, and spatial alignment between
      auditory and visual information. Experiments were run under realistic virtual
      environment. Participants were asked to react as fast as possible to a target
      object presented in the visual and/or the auditory modality and to inhibit a
      distractor object (go/no-go task). Spatial alignment had no effect on object
      recognition time. The only spatial effect observed was a stimulus-response
      compatibility between the auditory stimulus and the hand position. Reaction times
      were significantly shorter for semantically congruent bimodal stimuli than would
      be predicted by independent processing of information about the auditory and
      visual targets. Interestingly, this bimodal facilitation effect was twice as
      large as found in previous studies that also used information-rich stimuli. An
      interference effect was observed (i.e. longer reaction times to semantically
      incongruent stimuli than to the corresponding unimodal stimulus) only when the
      distractor was auditory. When the distractor was visual, the semantic
      incongruence did not interfere with object recognition. Our results show that
      immersive displays with large visual stimuli may provide large multimodal
      integration effects, and reveal a possible asymmetry in the attentional filtering
      of irrelevant auditory and visual information.

PMID- 19093107
TI  - Multi-scale calculation and global-fit analysis of hydrodynamic properties of
      biological macromolecules: determination of the overall conformation of antibody
      IgG molecules.
AB  - We present a scheme, based on existing and newly developed computational tools,
      for the determination of the overall conformation of biological macromolecules
      composed by domains or subunits, using from such structural determination easily
      available solution properties. In a multi-scale approach, atomic-level structures
      are used to provide simple shapes for the subunits, which are put together in a
      coarse grained model, with a few parameters that determine the overall shape of
      the macromolecule. Computer programs, like those in the HYDRO suite that evaluate
      the properties of either atomic or coarse-grained models. In this paper we
      present a new scheme for a global fit of multiple properties, implemented in a
      new computer program, HYDROFIT, which interfaces with the programs of the HYDRO
      suite to find an optimum, best-fitting structure in a robust but simple way. The
      determination of the overall structure of the native antibody IgG3, bearing a
      long hinge, and that of the hingeless mutant m15 is presented to test and confirm
      the validity of this simple, systematic and efficient scheme.

PMID- 19093108
TI  - An investigation of the reaction kinetics of luciferase and the effect of
      ionizing radiation on the reaction rate.
AB  - The bioluminescence produced by luciferase, a firefly enzyme, requires three
      substrates: luciferin, ATP and oxygen. We find that ionizing radiation, in the
      form of a proton beam from a cyclotron, will eliminate dissolved oxygen prior to
      any damage to other substrates or to the protein. The dose constant for removal
      of oxygen is 70 +/- 20 Gy, a much smaller dose than required to cause damage to
      protein. Removal of oxygen, which is initially in excess, leads to a sigmoidal
      response of bioluminescence to radiation dose, consistent with a Michaelis-Menten
      relationship to substrate concentration. When excess oxygen is exhausted, the
      response becomes exponential. Following the irradiation, bioluminescence recovers
      due to a slow leak of oxygen into the solution. This may also explain previous
      observations on the response of bioluminescent bacteria to radiation. We have
      studied the dependence of the reaction rate on enzyme and substrate concentration
      and propose a model for the reaction pathway consistent with this data. The light
      output from unirradiated samples decreases significantly with time due to product
      inhibition. We observe that this inhibition rate changes dramatically immediately
      after a sample is exposed to the beam. This sudden change of the inhibition rate
      is unexplained but shows that enzyme regulatory function responds to ionizing
      radiation at a dose level less than 0.6 Gy.

PMID- 19093109
TI  - FDG PET/CT findings in secondary hyperparathyroidism not mimicking multiple bone
      metastases.

PMID- 19093110
TI  - Comment on: Recombinant human TSH in differentiated thyroid cancer: a nuclear
      medicine perspective.

PMID- 19093111
TI  - Cancer-associated stroma affects FDG uptake in experimental carcinomas.
      Implications for FDG-PET delineation of radiotherapy target.
AB  - PURPOSE: To analyse the influence of cancer-associated stroma on FDG-uptake in
      two carcinoma models characterized by different stromal degrees. METHODS: Eight
      nude mice were subcutaneously injected with DU-145 prostate cancer cells or BXPC
      3 pancreatic cancer cells, and underwent FDG-PET imaging about 2 weeks after
      implantation. After the mice were killed, histology, and CD31 and GLUT1
      immunohistochemistry were performed. To further evaluate the highly stromalized
      carcinoma using perfusion-sensitive imaging, four BXPC-3 tumours underwent two
      successive albumin-binding (MS-325) MRI scans during tumour growth. RESULTS: FDG
      uptake was significantly higher in the DU-145 than in the BXPC-3 tumours, which
      were hardly distinguishable from adjacent normal tissue. In the BXPC-3 tumours,
      histology confirmed the widespread presence of aberrant infiltrated stroma,
      embedded with numerous vessels marked by CD31. In both tumour types, the stromal
      matrix was negative for GLUT1. In DU-145 tumour cells, GLUT1 immunostaining was
      greater than in BXPC-3 tumour cells, but not homogeneously, since it was less
      evident in the tumour cells which were nearer to vessels and stroma. Finally, MS
      325 MRI always clearly showed areas of enhancement in the BXPC-3 tumours.
      CONCLUSION: Cancer-associated stroma has been reported to be capable of aerobic
      metabolism with low glucose consumption. Furthermore, it has been proposed that
      regions with high vascular perfusion exhibit a significantly lower FDG uptake,
      suggesting some vascular/metabolic reciprocity. Since our results are consistent
      with these recent findings, they signal a risk of tumour volume underestimation
      in radiotherapy if FDG uptake alone is used for target delineation of carcinomas,
      which suggests that additional evaluation should be performed using
      vasculature/perfusion-sensitive imaging.

PMID- 19093112
TI  - Noninvasive functional imaging of P-glycoprotein-mediated doxorubicin resistance
      in a mouse model of hereditary breast cancer to predict response, and assign P-gp
      inhibitor sensitivity.
AB  - PURPOSE: Using a "spontaneous" mammary mouse tumor model we set out to develop
      diagnostic approaches for non-invasive P-glycoprotein (P-gp) staging and response
      prediction. METHODS: (99m)Tc-MIBI efflux rates were measured using a gamma camera
      in three Brca1 (-/-); p53 (-/-) mouse mammary tumors that have different Mdr1a/b
      expression levels. The efflux rates were quantified in the 10-30-min period after
      injection. In addition to the P-gp-mediated efflux measurements in untreated
      tumors, efflux measurements were performed in the presence of the P-gp inhibitor
      tariquidar. Volumetric doxorubicin response patterns for the different tumors
      were determined and correlated with the efflux rates. RESULTS: Combined pre- and
      post-inhibitor treatment imaging of P-gp-mediated efflux correlated with Mdr1a/b
      expression: basal (0.0026, p = 0.16), 3-fold Mdr1a/b (0.0074, p = 0.02), and 17
      fold Mdr1a and 46-fold Mdr1b (0.012, p = 0.002). Based on the doxorubicin
      response of these tumors, we generated a computer-aided diagnosis model that
      predicts the likelihood of drug resistance. CONCLUSIONS: Quantified (99m)Tc-MIBI
      efflux has potential to: (1) noninvasively assign Mdr1 expression levels, (2)
      predict the therapeutic impact of a P-gp inhibitor, and (3) noninvasively assess
      the probability of drug resistance.

PMID- 19093113
TI  - Usefulness of 18F-fluorodeoxyglucose positron emission tomography for diagnosing
      disease activity and monitoring therapeutic response in patients with pulmonary
      mycobacteriosis.
AB  - PURPOSE: To evaluate the usefulness of (18)F-FDG PET in the imaging of pulmonary
      lesions related to disease activity and in monitoring responses to treatment in
      patients with pulmonary mycobacteriosis (PM). MATERIALS AND METHODS: We used high
      resolution computed tomography (HRCT) and (18)F-FDG PET to evaluate 47
      consecutive untreated patients with PM, 25 with tuberculosis (TB) and 22 with
      Mycobacterium avium-intracellulare complex (MAC), who presented with small
      peripheral pulmonary nodules <or=3 cm, and compared the findings. The diagnosis
      of mycobacteriosis was confirmed by bacteriological examinations of bronchoscopic
      or surgically resected specimens. PET scans were visually and quantitatively
      analysed using SUVmax. In addition, 14 patients with PM underwent repeat PET
      scanning during antimycobacterial therapy, and changes in (18)F-FDG uptake were
      clinically evaluated (6 during treatment and 12 after treatment). RESULTS: Of all
      the lesions, 87.2% had SUVmax levels ranging from 3 to 7 (5.05 +/- 1.56, range
      2.5-7.6, n = 47). Further, SUV levels in patients with PM reflected disease
      activity as estimated by HRCT, but did not differ significantly between those
      with TB (4.96 +/- 1.61, n = 25) and MAC (5.15 +/- 1.53, n = 22). (18)F-FDG uptake
      was significantly decreased in all 14 patients who received chemotherapy,
      indicating a positive response to treatment. CONCLUSION: (18)F-FDG PET is
      considered to be useful for the diagnosis and evaluation of disease activity
      along with HRCT findings, and in monitoring response to chemotherapy in patients
      with PM.

PMID- 19093114
TI  - Hemoperitoneum due to spontaneous rupture of the left gastroepiploic artery in a
      patient with hemophilia A.

PMID- 19093115
TI  - Association of sickle avascular necrosis with bone morphogenic protein 6.

PMID- 19093116
TI  - Dermatomyositis, complicated with pneumomediastinum, successfully treated with
      cyclosporine A: a case report and review of literature.
AB  - We report a rare case of patient with dermatomyositis (DM) who developed
      spontaneous pneumomediastinum (PnM) and subcutaneous emphysema. She was
      successfully treated with oral prednisolone and cyclosporine A (CsA). We reviewed
      the cases of PnM in patients with DM treated with CsA. A review of four
      previously reported cases revealed that treatment with systemic glucocorticoid
      and CsA was effective for the DM and PnM. We indicate that initial and early
      treatment of the patients with DM and PnM with CsA enabled rapid tapering of the
      dose of glucocorticoid and improved the disease.

PMID- 19093117
TI  - An unusual central nervous system involvement in rheumatoid arthritis:
      combination of pachymeningitis and cerebral vasculitis.
AB  - Severe primary central nervous system (CNS) involvement such as vasculitis and
      pachymeningitis can rarely occur in rheumatoid arthritis (RA) even in the absence
      of systemic disease activation. The authors illustrate a female patient with well
      controlled RA who presented with headaches, encephalopathy, seizures and
      relapsing focal neurological deficits. Primary rheumatoid cerebral vasculitis and
      pachymeningitis were diagnosed based on suggestive brain magnetic resonance (MR)
      imaging, MR angiography, cerebrospinal fluid analysis and cerebral angiography.
      MR showed abnormal leptomeningeal enhancement and hyperintense FLAIR signal in
      the cortical subarachnoid spaces consistent with pachymeningitis. Cerebral
      angiography findings were consistent with vasculitis. Aggressive treatment
      resulted in significant clinicoradiological resolution. Cerebral vasculitis is a
      rare but certain manifestation of RA. This complication can be diagnosed in the
      presence of suggestive angiographic and CSF findings. The condition may be
      steroid resistant, and needs to be treated more aggressively.

PMID- 19093118
TI  - Pneumomediastinum and subcutaneous emphysema secondary to amyopathic
      dermatomyositis with cryptogenic organizing pneumonia in invasive breast cancer:
      a case report and review of literature.
AB  - Amyopathic dermatomyositis (ADM) is recognized as a variant phenotype of
      dermatomyositis and characterized by typical skin manifestations without evidence
      of muscular inflammation. While interstitial lung disease (ILD) is occasionally
      found as one of the lung manifestations in ADM patients, the development of a
      pneumomediastinum and/or subcutaneous emphysema in this disease entity is one of
      the extremely rare pulmonary complications. These latter complicated pulmonary
      manifestations have been usually reported in idiopathic ADM with ILD without any
      other associated medical conditions. We report a case presented with the
      spontaneous pneumomediastinum and subcutaneous emphysema in both ADM and
      cryptogenic organizing pneumonia during adjuvant chemotherapy based on
      cyclophosphamide for breast cancer.

PMID- 19093119
TI  - Evaluation of a morphological marker selection and excision system to generate
      marker-free transgenic cassava plants.
AB  - The efficacy of the ipt-type Multi-Auto-Transformation (MAT) vector system to
      transform the extensively grown cassava cultivar "KU50" was evaluated. This
      system utilizes the isopentenyltransferase (ipt) gene as morphological marker for
      visual selection of transgenic lines. The extreme shooty phenotype (ESP) of
      transgenic lines is lost due to the removal of ipt gene mediated by the yeast
      Rint/RS system. As a result, phenotypically normal shoots, considered marker-free
      transgenic plants, could be obtained. When transforming KU50 cassava cultivar
      with two different ipt-type MAT vectors, transformation frequency at 19-21% was
      observed. Among the total number of ESP explants, 32-38% regained normal extended
      shoot phenotype and 88-96% of which were confirmed to represent the marker-free
      transgenic plants. This is the first demonstration of the efficacy of Rint/RS
      system in promoting excision of ipt marker gene in cassava specie, with the
      consequent rapid production of marker-free transgenic plants. The high efficiency
      of this system should facilitate pyramiding a number of transgenes by repeated
      transformation without having to undergo through laborious, expensive and time
      consuming processes of sexual crossing and seed production. The generation of
      marker-free, thus environmentally safe, genetically modified cassava clones
      should also ease the public concerns regarding the use of transgenic cassava in
      both food and nonfood industries.

PMID- 19093120
TI  - A simple and sensitive high-throughput GFP screening in woody and herbaceous
      plants.
AB  - Green fluorescent protein (GFP) has been used widely as a powerful bioluminescent
      reporter, but its visualization by existing methods in tissues or whole plants
      and its utilization for high-throughput screening remains challenging in many
      species. Here, we report a fluorescence image analyzer-based method for GFP
      detection and its utility for high-throughput screening of transformed plants. Of
      three detection methods tested, the Typhoon fluorescence scanner was able to
      detect GFP fluorescence in all Arabidopsis thaliana tissues and apple leaves,
      while regular fluorescence microscopy detected it only in Arabidopsis flowers and
      siliques but barely in the leaves of either Arabidopsis or apple. The hand-held
      UV illumination method failed in all tissues of both species. Additionally, the
      Typhoon imager was able to detect GFP fluorescence in both green and non-green
      tissues of Arabidopsis seedlings as well as in imbibed seeds, qualifying it as a
      high-throughput screening tool, which was further demonstrated by screening the
      seedlings of primary transformed T(0) seeds. Of the 30,000 germinating
      Arabidopsis seedlings screened, at least 69 GFP-positive lines were identified,
      accounting for an approximately 0.23% transformation efficiency. About 14,000
      seedlings grown in 16 Petri plates could be screened within an hour, making the
      screening process significantly more efficient and robust than any other existing
      high-throughput screening method for transgenic plants.

PMID- 19093121
TI  - Unusually large oilbodies are highly correlated with lower oil content in
      Brassica napus.
AB  - Rapeseed cultivars exhibit a wide range of oil content in the mature seeds.
      Little is known about the relationship between the oilbody structures and the
      differences in oil contents of Brassica napus cultivars. In the present study,
      the oilbody morphology and its fate during the embryo development and seedling
      growth in several cultivars with oil contents ranging from 33.4 to 49.8% were
      studied. Cultivars with low oil contents (LO), some of the oilbodies were in
      similar size to those in cultivars with high oil content (HO), while some
      oilbodies in the LO cultivars were several times bigger (over 5.0 microm). These
      are much larger than the average size of B. napus seed oilbodies that were
      previously reported (Mantese et al. Ann Bot 97:999-1010, 2006). The oleosin
      protein levels and oleosin1 gene transcript abundances in the HO cultivars were
      clearly higher than in the LO cultivars. The shapes of oilbodies were similar
      during early stages of embryo development in both HO and LO cultivars, while as
      the embryos matured, the unusually large oilbodies were generated in the LO
      cells. After germination, the oilbodies in LO cultivars were consumed more slowly
      than in HO, and the seed germination rates of LO cultivars were less than those
      of HO cultivars. The low accumulation of oleosins results in the forming of
      unusually large oilbodies in LO cultivars.

PMID- 19093122
TI  - Intraindividual comparison of myocardial delayed enhancement MR imaging using
      gadobenate dimeglumine at 1.5 T and 3 T.
AB  - For contrast-enhanced imaging techniques relying on strong T1 weighting, 3 T
      provides increased contrast compared with 1.5 T. The aim of our study was the
      intraindividual comparison of delayed enhancement MR imaging at 1.5 T and at 3 T.
      Twenty patients with myocardial infarction were examined at 1.5 T and 3 T.
      Fifteen minutes after injection of contrast agent (0.1 mmol gadobenate
      dimeglumine per kg body weight), inversion recovery gradient recalled echo (IR
      GRE) sequences were acquired (1.5 T/3 T: TR 11.0/9.9 ms, TE 4.4/4.9 ms, flip 30
      degrees /30 degrees , slice thickness 6/6 mm) to assess myocardial viability. Two
      observers rated image quality (Wilcoxon signed rank test). Quantification of
      hyperenhanced myocardium and standardized SNR/CNR measurements were performed
      (Student's t test). There was no significant difference with respect to image
      quality (1.5 T/3 T: 3.5/3.3, p = 0.34, reader 1; 2.4/2.7, p = 0.12, reader 2) and
      infarction size (760 +/- 566/828 +/- 677 mm(2) at 1.5 T, 808 +/- 639/826 +/- 726
      mm(2) at 3 T, reader 1/reader 2, p > 0.05). Mean SNR in hyperenhanced/normal
      myocardium was 19.2/6.2 at 1.5 T and 29.5/8.8 at 3 T (p < 0.05). Mean CNR was
      14.3 at 1.5 T and 26.0 at 3 T (p < 0.05). Delayed enhancement MR imaging at 3 T
      is a robust procedure yielding superior tissue contrast at 3 T compared with 1.5
      T which is, however, not reflected by increased image quality.

PMID- 19093123
TI  - Responses of descending neurons to looming stimuli in the praying mantis Tenodera
      aridifolia.
AB  - Responses to visual stimuli of some neurons that descend the nerve cord from the
      brain were recorded extracellularly in the mantis Tenodera aridifolia. Most of
      the recorded neurons showed their largest responses to looming stimuli that
      simulated a black circle approaching towards the mantis. The neurons showed a
      transient excitatory response to a gradually darkening or receding circle. The
      neurons showed sustained excitation to the linearly expanding stimuli, but the
      spike frequency decreased rapidly. The responses of the neurons were affected by
      both the diameter and the speed of looming stimuli. Faster or smaller looming
      stimuli elicited a higher peak frequency. These responses were observed in both
      recordings from the connective between suboesophageal and prothoracic ganglia and
      the connective between prothoracic and mesothoracic ganglia. There was a one-to
      one correspondence of spike firing between these two recordings with a fixed
      delay. The neurons had the receptive field on ipsilateral side to its axon at the
      cervical connective. These results suggest that there is a looming-sensitive
      descending neuron, with an axon projecting over prothoracic ganglion, in the
      mantis nervous system.

PMID- 19093124
TI  - Responsiveness to photoperiodic changes in the circannual rhythm of the varied
      carpet beetle, Anthrenus verbasci.
AB  - The circannual pupation rhythm of Anthrenus verbasci is entrained to an
      environmental cycle by changes in photoperiod. Exposure of larvae reared under
      short-day conditions to 4 weeks of long days can induce phase-dependent phase
      shifts. In the present study, we examined the range of photoperiodic changes
      effective for phase shifts at 20 degrees C. For larvae under light/dark (LD)
      12:12 conditions, 4-week exposure to LD 14:10 caused a clear phase delay, as
      great an extent as that brought about by exposure to LD 15:9 and LD 16:8. In
      contrast, the delay brought about by exposure to LD 13:9 was slight. For larvae
      under LD 10:14, exposure to LD 14:10 and LD 16:8 for 4 weeks induced a phase
      delay, but exposure to LD 12:12 did not. These results indicate that a clear
      phase delay is induced when the photoperiodic change exceeds a critical value in
      the photophase between 13 and 14 h, regardless of the amplitude of the change.
      Although phase advances were smaller than phase delays, they depended on the
      amplitude of photoperiodic changes rather than the absolute photophase duration
      in contrast to the case of the phase delay.

PMID- 19093125
TI  - The function of wall-following behaviors in the Mexican blind cavefish and a
      sighted relative, the Mexican tetra (Astyanax).
AB  - Mexican blind cavefish exhibit an unconditioned wall-following behavior in
      response to novel environments. Similar behaviors have been observed in a wide
      variety of animals, but the biological significance and evolutionary history of
      this behavior are largely unknown. In this study, the behaviors of Mexican blind
      cavefish (Astyanax sp.) and sighted Mexican tetra (Astyanax mexicanus) were
      videotaped after fish were introduced into a novel environment under dark
      (infrared) or well-lit conditions. Under dark conditions, both sighted and blind
      morphs exhibited wall-following behaviors with subtle but significant
      differences. Blind morphs swam more nearly parallel to the wall, exhibited
      greater wall-following continuity and reached higher levels of sustained swimming
      speeds more quickly than sighted morphs. In contrast, sighted morphs in the light
      remained motionless near the wall for long periods of time or moved slowly around
      the center of the tank without entraining to the walls. These results are
      consistent with the idea that wall-following is a shared, primitive trait that
      serves an exploratory function under dark conditions to compensate for the
      absence of vision. This behavior has become more honed in blind morphs for
      exploratory purposes--in large part due to the enhanced, active-flow sensing
      abilities of the lateral line.

PMID- 19093126
TI  - [ANCA-associated vasculitides. Classifying the disease and its activity according
      to EULAR/EUVAS recommendations].

PMID- 19093127
TI  - [Cyclophosphamide versus bolus in Wegener's granulomatosis and other ANCA-related
      vasculitides: advantages and disadvantages].
AB  - Cyclophosphamide remains the therapy of choice in severe ANCA positive
      vasculitis. In order to avoid the considerable side effects of high cumulative
      doses sometimes manifesting themselves years later, induction therapy with a low
      cyclophosphamide dose and an early switch to cyclophosphamide-free maintenance
      regimens should be aimed for. This can be achieved by an induction therapy of 3-
      6 months of intravenous pulse therapy (pCYC) or oral therapy (oCYC). The
      metaanalysis of therapeutic trials in ANCA vasculitis demonstrates a slightly
      higher induction rate of remission, but an increased relapse rate of pCYC
      compared to oCYC. The incidence of adverse events seems to be higher in oCYC
      compared to pCYC. The results of the first controlled prospective multicenter
      trial (CYCLOPS) directly comparing pCYC and oCYC treatment of ANCA-positive
      vasculitis are eagerly awaited. It will be important to extend the follow-up over
      several years in order to reach a valid estimate of the incidence of secondary
      malignancies due to CYC therapy.

PMID- 19093128
TI  - [EULAR recommendations for the management of Behcet's disease. Report of a task
      force of the European Standing Committee for International Clinical Studies
      Including Therapeutics (ESCISIT)].
AB  - OBJECTIVES: The aim of the EULAR/ESCISIT initiative was to develop evidence-based
      recommendations for the management of Behcet's disease (BD), supplemented where
      necessary by expert opinions and taking already published data into
      consideration. The current article briefly summarises the results in German and
      comments on them. METHODS: The multidisciplinary expert committee consisted of
      nine rheumatologists, three ophthalmologists, one internist, one dermatologist,
      and one neurologist, representing six European countries, Tunisia and Korea. One
      patient representative was also present. Problem areas and related keywords for a
      systematic literature search were identified. A systematic literature research
      was performed using MedLine and the Cochrane library up to December 2006.
      Consequently, 40 initial statements were generated based on the literature
      research. These yielded the final recommendations which resulted from two blind
      Delphi rounds of voting. RESULTS: Nine recommendations were developed for the
      management of different aspects of BD. The strength of each recommendation was
      determined by the level of evidence and the expert's opinions. The level of
      agreement for each recommendation was determined using a visual analogue scale
      for both the whole committee and for each individual viewpoint of the subgroup,
      who considered themselves experts in that field of BD. There was excellent
      concordance between the level of agreement of the whole group and the "experts in
      the field". CONCLUSION: Recommendations relating to eye, skin, and mucosal
      disease, as well as arthritis are mainly evidence-based, while recommendations on
      vascular disease and neurological and gastrointestinal involvement are based
      largely on expert opinions and uncontrolled evidence from open trials and
      observational studies. The need for further properly designed controlled clinical
      trials is apparent.

PMID- 19093129
TI  - Relapse and survival in early-stage ovarian cancer.
AB  - OBJECTIVE: To analyze the prognostic influence of patient characteristics,
      diagnostic markers or therapeutic procedures in women diagnosed with early
      ovarian cancer based on relapse and survival in long term follow-up. MATERIALS
      AND METHODS: All women diagnosed and treated for early ovarian cancer at our
      institution between 1992 and 2006 were included in this retrospective study.
      Patient characteristics, clinical data including operative procedure, serum
      markers, stage and histology at first diagnosis as well as follow-up data were
      analyzed with regard to survival times and relapse rates. RESULTS: Altogether,
      116 patients were included. Mean follow-up time was 7.0 +/- 3.3 years (range 2-14
      years). Histology revealed a serous tumor in 64.7% (75/116), mucinous in 19.0%
      (22/116) and endometiroid tumors in 7.8% (9/116) of all cases. TNM classification
      was pT1a in 49.1% (57/116), pT1b in 6% (7/116), pT1c in 32.8% (38/116) and pT2a
      in 12.1% (14/116). Lymph node involvement (N1) was found in 3.4% of all patients.
      17 deaths and 17 relapses (each 14.7%) were documented during follow-up time with
      a mean time to recurrence of 3.3 +/- 2.1 years (range 1-7 years). The general 1-,
      2-, 5- and 10-year survival rates were 99, 95.7 and 88.9 and 81.0%, respectively.
      Patients with tumor stage pT1a and pT1b had a significantly better survival (P =
      0.0003) and significantly lower risk of recurrence (P = 0.0138) compared to
      higher tumor stages. Moreover, patients who experienced recurrent disease or
      presented with ascites at primary diagnosis had a significantly worse overall
      survival (recurrence: hazard ratio 0.17, 95% confidence interval 0.0155-0.2182, P
      = 0.0001; ascites: HR 2.84, CI 1.1919-10.1131, P = 0.0225). The risk for
      recurrent disease was significantly elevated for patients with low grade (G3)
      tumors (P = 0.0330). Interestingly, there was neither a worse survival rate nor a
      higher relapse rate for patients with primary laparoscopic surgical access.
      CONCLUSION: Patients with early ovarian cancer stage pT1c and pT2a or low grade
      tumor have to be monitored closely in oncologic follow-up as they bare a
      significant risk for disease recurrence. Ascites at primary diagnosis, pT1c or
      pT2a tumor stage or recurrent disease are associated with a poor survival even in
      early ovarian cancer.

PMID- 19093130
TI  - The incidence of adenoidal regrowth after adenoidectomy and its effect on
      persistent nasal symptoms.
AB  - Objective of the study is to evaluate the effectiveness of adenoidectomy for
      children, to asses the rates of adenoidal regrowth and find out if the regrowth
      of adenoidal tissue affects persistent nasal symptoms post-surgery. A prospective
      study was carried out in the period of 2005-2007. The inclusion criteria for
      patients in the study were hypertrophic adenoid tissue and moderate or severe
      persistent nasal obstruction. One hundred and fifty children had undergone an
      adenoidectomy using consistent technique and visual control. Medium-term follow
      up results were conducted 12-24 months (the mean follow-up period was 17.1
      months) post-surgery, performing transnasal fibroscopy and completing the
      questionnaire. A total of 104 (69.3%) out of 150 patients polled. Children's
      parents answered the questions that were used for the subjective assessment of
      symptoms and to ascertain the history of the patient's nasal obstruction and
      upper respiratory tract infection prior to surgery. The age range was from 3 to
      15, of which, 68 (65.3%) of them had undergone a transnasal fibroscopy. There was
      a significant reduction in symptoms that were displayed by children prior to the
      operation: there were 5.8% patients with nasal obstruction after the surgery,
      while incidences of upper airway infections dropped from 79.8 to 7.7% after
      surgery (P < 0.001). Eighty-six (82.7%) parents considered their child's well
      being as "having improved" and they were "satisfied" with the results. Transnasal
      fibroscopy examinations identified some regrowth of adenoidal tissue in 13 cases
      (19.1%), with only 3 cases demonstrating adenoidal regrowth to grade 1. Adenoidal
      regrowth was correlative with the age of the patients (P = 0.048) and to numerous
      postoperative treatment with antibiotics (P = 0.032). Adenoids rarely regrow
      after surgery and where there were traces of adenoidal tissue, it did not
      manifest clinically. Nasal obstruction after the adenoidectomy is rhinogenic
      origin, not the cause of enlarged adenoids. Adenoidal regrowth more often occurs
      in children younger than five years old and in those patients who were treated
      postoperatively with antibiotics on numerous occasions.

PMID- 19093131
TI  - Pleural and pericardial morbidity after minimal access repair of pectus
      excavatum.
AB  - PURPOSE: The aim of this study was to evaluate the pleural and pericardial
      morbidity in patients that had undergone pectus excavatum corrections using
      minimal access repair of pectus excavatum (MARPE) at a single center. MATERIALS
      AND METHODS: Data from patients after MARPE from 2000 to 2007 were prospectively
      collected. Patients with pneumothorax and pleural and pericardial effusions were
      identified. RESULTS: One hundred eighty patients were corrected by MARPE. Eighty
      four were identified to have pleural or pericardial morbidities. Pneumothorax was
      documented in 33 patients and five required placement of a chest tube. Pleural
      effusions were recorded in 53 and were found to recur in four patients. Drainage
      was necessary in 18 patients. Pericardial effusions were observed in five
      patients; in two cases, they were associated with recurring pleural effusions,
      suggesting postcardiomyotomy syndrome. CONCLUSIONS: MARPE is associated with a
      high rate of pleural and pericardial morbidities, but only a small number
      requires interventions.

PMID- 19093132
TI  - Cyclic AMP decreases the production of NO and CCL2 by macrophages stimulated with
      Trypanosoma cruzi GPI-mucins.
AB  - Glycosylphosphatidylinositol-anchored mucin-like glycoproteins (tGPI-mucin)
      present on the surface of the cellular membrane of Trypanosoma cruzi forms
      activate toll-like receptors 2 (TLR2) on the surface of immune cells and induce
      the release of several mediators of inflammation which may be relevant in the
      context of Chagas disease. Here, we evaluated the ability of tGPI-mucins to
      activate murine peritoneal macrophages to induce nitric oxide (NO) and monocyte
      chemoattractant protein-1 (MCP-1/CCL2). We also investigated the ability of
      compounds which increase or mimic cyclic adenosine monophosphate (AMP) to
      modulate the production of NO and CCL2. Our data show that elevation of
      intracellular levels of cyclic AMP prevents the release of NO and CCL2 induced by
      tGPI-mucins in macrophages. Overall, the release of CCL2 was decreased to a
      greater extent and at lower concentrations of cyclic AMP-modifying agents than
      the production of NO. It is suggested that the elevation of cyclic AMP during T.
      cruzi infection may modify the release of pro-inflammatory mediators and alter
      significantly the course of T. cruzi infection.

PMID- 19093133
TI  - Synchronization of occurrence of the ovarian philometrid, Philometra
      carolinensis, with the spawning season of its fish host, the spotted seatrout,
      Cynoscion nebulosus.
AB  - The philometrid Philometra carolinensis inhabits the ovaries of the spotted
      seatrout, Cynoscion nebulosus. A 2-year study in estuaries of South Carolina
      showed that each year adult female worms were present only during the spawning
      season of the host and that only sexually mature fish were infected. Overall
      prevalence was 13.1%. Young-of-the-year fish were uninfected and mature 1-year
      old fish were less frequently infected than older fish. Abundance of the
      philometrid was significantly different in age-1 and -2 spotted seatrout.
      Prevalence, mean abundance, and intensity peaked during the first 2 months of the
      host's 4-month spawning season, which then declined abruptly. Occurrence of the
      philometrid in the fish host was unaffected by water temperature, salinity, and
      dissolved oxygen. Histological studies revealed that the worms were
      hematophagous. Worms induced disruption of the ovarian lamellar walls resulting
      in the interruption of development and the loss of host eggs into the ovarian
      lumen prior to their maturation. The data show that development of this parasite
      is linked to the host's reproductive status and suggest that paratenesis plays an
      important role in the maintenance of the parasite's life cycle.

PMID- 19093134
TI  - The Tnt1 family member Retrosol copy number and structure disclose
      retrotransposon diversification in different Solanum species.
AB  - Eukaryotic genome expansion/retraction caused by LTR-retrotransposon activity is
      dependent on the expression of full length copies to trigger efficient
      transposition and recombination-driven events. The Tnt1 family of
      retrotransposons has served as a model to evaluate the diversity among closely
      related elements within Solanaceae species and found that members of the family
      vary mainly in their U3 region of the long terminal repeats (LTRs). Recovery of a
      full length genomic copy of Retrosol was performed through a PCR-based approach
      from wild potato, Solanum oplocense. Further characterization focusing on both
      LTR sequences of the amplified copy allowed estimating an approximate insertion
      time at 2 million years ago thus supporting the occurrence of transposition
      cycles after genus divergence. Copy number of Tnt1-like elements in Solanum
      species were determined through genomic quantitative PCR whereby results sustain
      that Retrosol in Solanum species is a low copy number retrotransposon (1-4
      copies) while Retrolyc1 has an intermediate copy number (38 copies) in S.
      peruvianum. Comparative analysis of retrotransposon content revealed no
      correlation between genome size or ploidy level and Retrosol copy number. The
      tetraploid cultivated potato with a cellular genome size of 1,715 Mbp harbours
      similar copy number per monoploid genome than other diploid Solanum species (613
      884 Mbp). Conversely, S. peruvianum genome (1,125 Mbp) has a higher copy number.
      These results point towards a lineage specific dynamic flux regarding the history
      of amplification/activity of Tnt1-like elements in the genome of Solanum species.

PMID- 19093135
TI  - Evaluation of the effects of the parameters involved in the purification of
      clavulanic acid from fermentation broth by aqueous two-phase systems.
AB  - The purification of clavulanic acid (CA), which is an important beta-lactam
      antibiotic produced by submerged cultivation of Streptomyces clavuligerus, was
      studied through the use of phosphate and polyethylene glycol-based aqueous two
      phase systems. The parameters' effect on the yield and purification was evaluated
      through an experimental design and the preliminary results showed that the
      polyethylene molecular mass and tie-line length and phase volume ratio exerted
      the strongest effect on the yield and distribution coefficient in the range
      tested. In addition, the response surface methodology was used to optimize the
      distribution coefficient, yield, and purification factor. The optimal conditions
      of yield and purification factor are in the regions where polyethylene has a low
      molecular mass, pH close to the isoelectric point, and lower top phase volume. A
      100% yield and a 1.5-fold purification factor are obtained when extracting CA by
      maximizing the conditions of an aqueous two-phase system.

PMID- 19093138
TI  - A pilot study of twice-weekly exercise during hemodialysis in children.
AB  - Few published studies have assessed the exercise capacity and/or the effect of
      exercise in children receiving maintenance hemodialysis (HD). The aim of this
      study was to determine if twice-weekly exercise for 1 h during HD could improve
      exercise capacity in children receiving HD. We assessed lower extremity strength
      (Biodex; dominant extension peak torque in 60 degrees per second, Newton-meters),
      grip strength (dynanometer, kilogram) and 6-min walk capacity (yards) in ten
      children (median age 13.6 years, range 8-25 years) at baseline and after 3 months
      of twice weekly exercise for 1 h during HD. Baseline assessment revealed a mean
      (1) Biodex of 70 +/- 32 N-m/s, (2) 6-m walk test of 589 +/- 90 yards and (3) grip
      strength of 23.2 +/- 10 kg, which were 50% lower than the normal value for
      healthy controls. Patients demonstrated significant improvements in lower
      extremity strength and 6-min walk test after 3 months of exercise. Our data show
      that twice-weekly exercise of a moderate intensity during HD can lead to exercise
      capacity improvement in 3 months. We identified barriers to and strategies for
      the successful implementation of intradialytic exercise. We suggest that
      intradialytic exercise intervention may be effective to improve exercise capacity
      in children receiving maintenance HD.

PMID- 19093136
TI  - Childhood extraordinary daytime urinary frequency-a case series and a systematic
      literature review.
AB  - Childhood extraordinary daytime urinary frequency is likely a common but
      underreported condition characterized by daytime frequent voiding and typically
      not linked with complaints of burning, urinary incontinence, altered urinary
      stream, changes in the nighttime voiding pattern, excessive fluid intake and
      excessive urinary volume. To determine the features and outcome of extraordinary
      daytime urinary frequency, we report our experience with 14 children and the
      results of a formal systematic analysis of peer-reviewed English-language
      literature on this topic. Nineteen case series were found (together with 16
      mostly pertinent comments), with each case series providing details on from one
      to 119 children. On the basis of our experience and the findings of our
      systematic analysis, we conclude that, in general practice, extraordinary daytime
      urinary frequency is a common cause of urinary frequency, that the age of such
      patients is, on average, 6 years and that the micturation abnormalities persist
      for an average of 6 months. The results of this review must be viewed with an
      understanding of the limitations of the analysis process, which incorporated data
      exclusively from case series.

PMID- 19093139
TI  - Mycophenolic acid inhibits oleic acid-induced mesangial cell activation through
      both cellular reactive oxygen species and inosine monophosphate dehydrogenase 2
      pathways.
AB  - The synthesis of extracellular matrix (ECM) in mesangial cells (MCs) plays
      important roles in the development and progression of renal diseases, including
      chronic allograft nephropathy. Mycophenolic acid (MPA), an inhibitor of inosine
      monophosphate dehydrogenase 2 (IMPDH2), suppresses MC proliferation and ECM
      synthesis. However, the exact inhibitory mechanism of MPA on MCs has not been
      clearly elucidated. In this study we compared the inhibitory effects of MPA and
      IMPDH2 reduction [by using small interfering RNA (siRNA)] on oleic acid (OA)
      induced fibronectin secretion and cellular reactive oxygen species (ROS) in mouse
      MCs. Growth-arrested MCs were stimulated with OA in the presence or absence of
      MPA, IMPDH2 siRNA, N-acetylcysteine (NAC), transforming growth factor beta (TGF
      beta) antibody or exogenous guanosine. Fibronectin secretion into the medium was
      examined by Western blot, dichlorodihydrofluorescein (DCF)-sensitive cellular ROS
      by fluorescence-activated cell scanning (FACS), TGF-beta levels in the media by
      enzyme-linked immunosorbent assay (ELISA). OA increased fibronectin secretion,
      TGF-beta and cellular ROS levels. A TGF-beta neutralizing antibody effectively
      suppressed OA-induced fibronectin secretion. NAC and MPA completely suppressed OA
      induced fibronectin secretion and decreased the levels of TGF-beta and cellular
      ROS. However, IMPDH2 siRNA partly inhibited OA-induced MC activation. Exogenous
      guanosine successfully reversed the inhibitory effects of IMPDH2 siRNA on OA
      induced MC activation. Pleiotropic inhibitory effect of MPA on OA-induced mouse
      MC activation was mediated via its antioxidant effect on cellular ROS production
      and partly via inhibition of IMPDH2 itself. Our results implicate ROS as an
      alternative therapeutic target for the prevention of hyperlipidemia-related
      glomerulopathy, chronic allograft nephropathy, and subsequent graft loss.

PMID- 19093140
TI  - Acanthamoeba T4 and T15 genotypes associated with keratitis infections in Italy.
AB  - Thus far there is little data available concerning Acanthamoeba associated
      amoebic keratitis (AK) from Italy. In order to understand the incidence of
      Acanthamoeba in patients with ocular infections and to characterize the isolates
      at the molecular level, ocular specimens and contact lenses or lens case
      solutions from 140 patients were analysed by culture and by an 18S rRNA (Rns)
      gene-based PCR method. Nineteen (13.6%) patients showed Acanthamoeba culture
      positive samples. Eleven out of the 14 genetically characterized isolates were
      assigned to the T4 genotype. Three isolates, two of them from patients with
      keratitis responding to specific anti-Acanthamoeba therapy, were identified as
      belonging to the T15 genotype. This finding represents the first association
      between the T15 genotype and human amoebic keratitis. PCR amplification of the
      18S ribosomal DNA proved to be a sensitive method, potentially able to detect
      Acanthamoeba without the need of long culture incubation, and thus considerably
      useful for clinical applications.

PMID- 19093141
TI  - Overall reduction in antibody production could contribute to generate pathogenic
      autoantibodies and autoimmune manifestations.

PMID- 19093143
TI  - Safety of ultrasound-assisted liposuction: a survey of 660 operations.
AB  - BACKGROUND: Ultrasound-assisted liposuction (UAL), although providing some
      advantages over tumescent liposuction (TL) and traditional or suction-assisted
      liposuction (SAL), has been found to have some controversial complications. We
      performed this study to evaluate UAL's complications and to compare UAL with the
      previous routine techniques for liposuction. METHODS: Six hundred sixty UALs were
      performed on 609 consecutive volunteers by one cosmetic surgeon. Demographic
      characteristics, local and systemic complications, and also severe adverse events
      (SAE) were registered intraoperatively and at 1, 4, and 12 weeks postoperatively.
      RESULTS: No SAEs were identified and only nine complications, consisting of two
      systemic complications (two cases of hypotension) and seven local complications
      (3 seromas, 3 cases of contact dermatitis, and 1 case of hemorrhage), were
      registered. This yields a complication incidence of 1.36%. There was no
      association between the number of complications and the body region, age, gender,
      or body mass index (BMI). CONCLUSION: Our findings are in line with others in
      that performing UAL using local tumescent anesthesia is a safe procedure with a
      very low complication rate and has remarkable advantages over other liposuction
      techniques (TL and SAL). In addition, there was no correlation between the
      incidence of complications and body region, age, gender, or BMI.

PMID- 19093142
TI  - Quantitative alterations of CD8+ T cells in juvenile idiopathic arthritis
      patients in remission.
AB  - The study was aimed to investigate whether quantities of CD8(+) T cell subsets
      are normal in juvenile idiopathic arthritis (JIA) patients with disease remission
      compared to age-matched healthy donors (HD) and whether chronological age may
      have an impact on proportions of naive CD8(+) T cells. CD8(+) T cell subsets were
      analyzed in 17 JIA patients and 32 age-matched HD by flow cytometry. JIA patients
      showed lower CD3(+)CD8(+) T cells compared to HD. Total counts of CD8(+)CD28(+)
      and CD8(+)CD28(+)CD45RA(+) T cells were inversely correlated to chronological age
      in JIA patients and HD. In JIA patients, percentages of CD8(+)CD28(+)CD45RA(+) T
      cells and of CD62L-expressing CD8(+)CD28(+)CD45RA(+) T cells showed a negative
      correlation with age. The trend to lower CD28(+)CD45RA(+) T cell proportions in
      aged JIA patients in remission may reflect a disturbed T cell homeostasis
      independently of disease activity and may be due to an intrinsic effect in
      reconstitution of the peripheral T cells.

PMID- 19093144
TI  - Minimally invasive combined treatment for Parry-Romberg syndrome.
AB  - BACKGROUND: Facial hemiatrophy, a typical manifestation of Parry-Romberg
      syndrome, produces massive face asymmetry, causing marked aesthetic damage and
      severe psychological discomfort, with repercussions to the psychophysical status
      of the patient. This article presents a successful combined treatment that
      results in resolution of symptoms and patient satisfaction. METHODS: The authors
      proposed a clinic-therapeutic management comprising a customized program of bio
      lipo-intense pulsed light (IPL) remodeling. RESULTS: In 2007, at a 1-year follow
      up visit, the patient presented a stable result. She is satisfied with the
      augmentation treatment, the new volume and contours of the face, and the
      resolution of the sclerosis and ochrodermia. CONCLUSION: The authors have
      succeeded with a minimally invasive reconstructive technique for Romberg disease
      using a customized therapeutic program of poly-L-lactic acid, lipofilling, and
      IPL therapy. They report a case of good healing without recurrences and
      complications, with a good cosmetic result, and with satisfaction of the patient.

PMID- 19093145
TI  - Hemostatic step-by-step procedure to control presacral bleeding during
      laparoscopic total mesorectal excision.
AB  - BACKGROUND: A new procedure of hemostasis during laparoscopic total mesorectal
      excision is described. METHODS: In our surgical department, from January 2004 to
      December 2007, 128 patients underwent laparoscopic total mesorectal excision.
      Among them, 47 patients underwent laparoscopic anterior resection after
      preoperative radiotherapy, 68 patients underwent laparoscopic anterior resection
      without preoperative radiotherapy, and 13 patients underwent laparoscopic
      abdominal perineal amputation. RESULTS: In seven laparoscopic rectal surgery
      cases, we encountered unstoppable presacral bleeding, not amenable by
      conventional hemostatic solutions. In these cases we applied a simple staging
      hemostatic procedure. We first performed local compression: tamponing with a
      small gauze or absorbable fabric hemostat. If bleeding did not stop, we localized
      an epiploic or omental scrap and excised it by using bipolar forceps and use it
      as a plug on the tip of a grasping forceps. This plug is then put on the bleeding
      source and monopolar coagulation is applied by electrified dissecting forceps
      through the interposed grasping forceps. If bleeding did not stop, we used a
      little scrap of bovine pericardium graft and tacked it to the bleeding site using
      endoscopic helicoidal protack. CONCLUSIONS: Our experience suggests that this
      hemostatic step-by-step procedure is a valid option to control persistent
      presacral hemorrhages.

PMID- 19093146
TI  - Percutaneous transhepatic cutting balloon papillotomy for removal of common bile
      duct stones.
AB  - We report the case of a 66-year-old female who presented with jaundice secondary
      to recurrent adenocarcinoma of the gallbladder and several common bile duct
      stones. Percutaneous papillary dilatation was planned to remove the common bile
      duct stones. Papilla was dilated through the percutaneous approach with an 8-mm
      peripheral cutting balloon instead of a standard balloon. All the stones were
      pushed successfully into the duodenum with a saline flush. No complications were
      encountered. Use of a peripheral cutting balloon for dilatation of the papilla
      seems to be safe and effective because it has the advantage of controlled
      incision and dilatation of the target at low pressures.

PMID- 19093147
TI  - Acute hemobilia after bilioplasty due to hepatic artery pseudoaneurysm: treatment
      with an ePTFE-covered stent.

PMID- 19093149
TI  - Identification and characterization of an autolysin gene, atlh, from
      Streptococcus downei.
AB  - An autolysin gene, atlh, was identified and sequenced from Streptococcus downei
      MFe28 using degenerate polymerase chain reaction (PCR) and the gene-walking
      method. Atlh protein encoded by atlh is composed of 879 amino acids, with a
      molecular weight of 95,902.26. Atlh possesses four 15-amino-acid residue repeats
      in the putative cell-wall-binding domain and has a catalytic domain in the C
      terminus. The deduced amino acid sequence of atlh showed homology to S. mutans
      autolysin AtlA (68.4% similarity). Inactivation of atlh resulted in elongated
      chain formation compared to the parent strain. Recombinant proteins Atlh and its
      derivatives were constructed and analyzed by zymography. Zymographic analysis
      revealed that the Asp-771 residue of Atlh was essential for lytic activity and
      that lytic activity was not diminished by the deletion of repetitive regions in
      the putative cell-wall-binding domain of Atlh. Biofilm assay showed that the wild
      type strain formed glucose- and sucrose-dependent biofilms, the atlh mutant
      diminished this ability. These results suggest that Atlh is associated with cell
      separation and biofilm formation.

PMID- 19093148
TI  - AMS INSIGHT--absorbable metal stent implantation for treatment of below-the-knee
      critical limb ischemia: 6-month analysis.
AB  - Endoluminal treatment of infrapopliteal artery lesions is a matter of
      controversy. Bioabsorbable stents are discussed as a means to combine mechanical
      prevention of vessel recoil with the advantages of long-term perspectives. The
      possibility of not having a permanent metallic implant could permit the
      occurrence of positive remodeling with lumen enlargement to compensate for the
      development of new lesions. The present study was designed to investigate the
      safety of absorbable metal stents (AMSs) in the infrapopliteal arteries based on
      1- and 6-month clinical follow-up and efficacy based on 6-month angiographic
      patency. One hundred seventeen patients with 149 lesions with chronic limb
      ischemia (CLI) were randomized to implantation of an AMS (60 patients, 74
      lesions) or stand-alone percutaneous transluminal angioplasty (PTA; 57 patients,
      75 lesions). Seven PTA-group patients "crossed over" to AMS stenting. The study
      population consisted of patients with symptomatic CLI (Rutherford categories 4
      and 5) and de novo stenotic (>50%) or occlusive atherosclerotic disease of the
      infrapopliteal arteries who presented with a reference diameter of between 3.0
      and 3.5 mm and a lesion length of <15 mm. The primary safety endpoint was defined
      as absence of major amputation and/or death within 30 days after index
      intervention and the primary efficacy endpoint was the 6-month angiographic
      patency rate as confirmed by core-lab quantitative vessel analysis. The 30-day
      complication rate was 5.3% (3/57) and 5.0% (3/60) in patients randomized for PTA
      alone and PTA followed by AMS implantation, respectively. On an intention-to
      treat basis, the 6-month angiographic patency rate for lesions treated with AMS
      (31.8%) was significantly lower (p = 0.013) than the rate for those treated with
      PTA (58.0%). Although the present study indicates that the AMS technology can be
      safely applied, it did not demonstrate efficacy in long-term patency over
      standard PTA in the infrapopliteal vessels.

PMID- 19093150
TI  - Overexpression of the chitosanase gene in Fusarium solani via Agrobacterium
      tumefaciens-mediated transformation.
AB  - To overexpress the chitosanase gene (csn) in F. solani, a vector based on pCAMBIA
      1300 was constructed. The csn gene, which is under control of the Aspergillus
      nidulans gpdA promoter and A. nidulans trpC terminator, was introduced back into
      the F. solani genome by Agrobacterium tumefaciens-mediated transformation, and
      the herbicide-resistance gene bar from Streptomyces hygroscopicus was used as the
      selection marker. Transformants which showed a significant increase in
      chitosanase production (approximately 2.1-fold than control) were obtained.
      Southern blot analysis indicated that most transformants had a single-copy T-DNA
      integration.

PMID- 19093151
TI  - Variation in the phase of response to low-frequency pure tones in the guinea pig
      auditory nerve as functions of stimulus level and frequency.
AB  - The directionality of hair cell stimulation combined with the vibration of the
      basilar membrane causes the auditory nerve fiber action potentials, in response
      to low-frequency stimuli, to occur at a particular phase of the stimulus
      waveform. Because direct mechanical measurements at the cochlear apex are
      difficult, such phase locking has often been used to indirectly infer the basilar
      membrane motion. Here, we confirm and extend earlier data from mammals using sine
      wave stimulation over a wide range of sound levels (up to 90 dB sound pressure
      level). We recorded phase-locked responses to pure tones over a wide range of
      frequencies and sound levels of a large population of auditory nerve fibers in
      the anesthetized guinea pig. The results indicate that, for a constant frequency
      of stimulation, the phase lag decreases with increases in the characteristic
      frequency (CF) of the nerve fiber. The phase lag decreases up to a CF above the
      stimulation frequency, beyond which it decreases at a much slower rate. Such
      phase changes are consistent with known basal cochlear mechanics. Measurements
      from individual fibers showed smaller but systematic variations in phase with
      sound level, confirming previous reports. We found a "null" stimulation frequency
      at which little variation in phase occurred with sound level. This null frequency
      was often not at the CF. At stimulation frequencies below the null, there was a
      progressive lag with sound level and a progressive lead for stimulation
      frequencies above the null. This was maximally 0.2 cycles.

PMID- 19093153
TI  - Surveillance chest X-rays for melanoma: prescription or proscription?

PMID- 19093152
TI  - Isolation of three diterpenoid acids from sunflowers, as oviposition stimulants
      for the banded sunflower moth, Cochylis hospes.
AB  - The banded sunflower moth (BSFM), Cochylis hospes Walshingham (Lepidoptera:
      Cochylidae) is a specialist insect, the larvae of which feed on sunflowers,
      Helianthus spp., and a few other species of Compositae. It is one of the most
      important pests of sunflower in the USA. Previous work on H. annuus, the
      cultivated sunflower, revealed two diterpenoids that function as oviposition
      stimulants for female BSFM, and that other, more polar compounds also stimulated
      oviposition. Using a bioassay-guided approach, we isolated three additional
      diterpenoids, grandifloric acid (1), 15beta-hydroxy-ent-trachyloban-19-oic acid
      (2), and 17-hydroxy-16alpha-ent-kauran-19-oic acid (3), from polar fractions of
      pre-bloom sunflower head extracts. In laboratory bioassays, purified natural
      samples of each of these compounds stimulated oviposition by female BSFM.
      Structure-activity relationships of the five diterpenoids known to stimulate
      oviposition by female BSFM are discussed.

PMID- 19093154
TI  - Variations in axillary staging: much ado about nothing?

PMID- 19093155
TI  - A mathematical model of liver cell aggregation in vitro.
AB  - The behavior of mammalian cells within three-dimensional structures is an area of
      intense biological research and underpins the efforts of tissue engineers to
      regenerate human tissues for clinical applications. In the particular case of
      hepatocytes (liver cells), the formation of spheroidal multicellular aggregates
      has been shown to improve cell viability and functionality compared to
      traditional monolayer culture techniques. We propose a simple mathematical model
      for the early stages of this aggregation process, when cell clusters form on the
      surface of the extracellular matrix (ECM) layer on which they are seeded. We
      focus on interactions between the cells and the viscoelastic ECM substrate.
      Governing equations for the cells, culture medium, and ECM are derived using the
      principles of mass and momentum balance. The model is then reduced to a system of
      four partial differential equations, which are investigated analytically and
      numerically. The model predicts that provided cells are seeded at a suitable
      density, aggregates with clearly defined boundaries and a spatially uniform cell
      density on the interior will form. While the mechanical properties of the ECM do
      not appear to have a significant effect, strong cell-ECM interactions can
      inhibit, or possibly prevent, the formation of aggregates. The paper concludes
      with a discussion of our key findings and suggestions for future work.

PMID- 19093156
TI  - Giant lipoma of the thenar--case study and contemporary approach to its
      aetiopathogenicity.
AB  - Giant lipomas of the thenar are rare tumours of the adipose tissue of the hand,
      with a benign prognosis. Apart from the cosmetic problems they may cause, their
      most frequent complications include a compromise in functionality and pressure
      upon the nerves, mainly on the radial nerve. The first step in their management
      is their differential diagnosis from well-differentiated liposarcomas (WDLPS), as
      they require a different therapeutic approach. This step is completed with the
      aid of MRIs, biopsies and modern immunohistochemical methods, which offer high
      specificity and sensitivity. Our paper presents a case of giant lipoma of the
      thenar, with a review of the relevant literature, focusing on the disease's
      molecular genetics, which is a very important field of research today.

PMID- 19093157
TI  - Factors associated with first-fill adherence rates for diabetic medications: a
      cohort study.
AB  - BACKGROUND: Little is known about first-fill adherence rates for diabetic
      medications and factors associated with non-fill. OBJECTIVE: To assess the
      proportion of patients who fill their initial prescription for a diabetes
      medication, understand characteristics associated with prescription first-fill
      rates, and examine the effect of first-fill rates on subsequent A1c levels.
      DESIGN: Retrospective, cohort study linking electronic health records and
      pharmacy claims. PARTICIPANTS: One thousand one hundred thirty-two patients over
      the age of 18 who sought care from the Geisinger Clinic, had Geisinger Health
      Plan pharmacy benefits, and were prescribed a diabetes medication for the first
      time between 2002 and 2006. MEASUREMENTS: The primary outcome of interest was
      naive prescription filled by the patient within 30 days of the prescription order
      date. RESULTS: The overall first-fill adherence rate for antidiabetic drugs was
      85%. Copays < $10 (OR 2.22, 95% CI 1.57-3.14) and baseline A1c > 9% (OR 2.63, 95%
      CI 1.35, 5.09) were associated with improved first-fill rates while sex, age, and
      co-morbidity score had no association. A1c levels decreased among both filling
      and non-filling patients though significantly greater reductions were observed
      among filling patients. Biguanides and sulfonylureas had higher first-fill rates
      than second-line oral agents or insulin. CONCLUSIONS: First-fill rates for
      diabetes medication have room for improvement. Several factors that predict non
      filling are readily identifiable and should be considered as possible targets for
      interventions.

PMID- 19093158
TI  - The recurrent clubfoot: can gait analysis help us make better preoperative
      decisions?
AB  - Gait patterns in children with recurrent clubfoot are often associated with more
      or less subtle factors contributing to the patterns, such as tibial torsion that
      might not be detected by visual observation and therefore not considered in a
      treatment plan. We therefore used gait analysis to elucidate the contributions to
      recurrent clubfoot deformity and to determine whether gait analysis could be
      important in preoperative decision-making for these patients. We reviewed all 35
      patients (56 feet) referred to our gait laboratory for recurrent deformity
      following treatment of idiopathic clubfoot. The average age of the children in
      our series was 6.7 years (range, 3.6-15.4 years). Data were acquired from
      computerized motion analysis, dynamic electromyography, and static measurements
      by a physical therapist. We found a high incidence of transverse plane
      deformities including intoeing in 45 of 56 feet (80%), internal tibial torsion in
      40 of 56 feet (71%), and forefoot adductus in 40 of 56 feet (71%). Forty feet
      were supinated in stance; of these patients, 28 (70%) had overactive tibialis
      anterior muscle activity based on dynamic EMG. Dynamic compensatory hip external
      rotation was present in 28 of 56 (50%) of limbs. Thirty of the 35 patients
      underwent surgery following gait analysis; the most common procedures included
      split anterior tibial tendon transfers (34), tibial derotational osteotomies
      (34), and midfoot osteotomies (20). Quantitative gait analysis resulted in 28
      changed procedures in 19 of 30 patients (63%) compared to prestudy surgical
      plans. LEVEL OF EVIDENCE: Level IV, therapeutic study. See the Guidelines for
      Authors for a complete description of levels of evidence.

PMID- 19093161
TI  - Effects of soy isoflavone consumption on bone structure and milk mineral
      concentration in a rat model of lactation-associated bone loss.
AB  - BACKGROUND: Like menopause, during complete lactation, circulating estrogen
      concentrations are markedly reduced, resulting in amplified bone resorption. AIM
      OF STUDY: To investigate the effects of soy isoflavones, common dietary
      components used to mitigate the bone loss of menopause, on the bone loss
      associated with lactation. METHODS: Lactating rats were randomized to one of four
      diets supplemented with different levels of soy isoflavones (0, 2, 4, 8 mg
      aglycone isoflavone/g protein). Milk was collected from all dams between days 12
      and 15 of lactation and was analyzed for calcium, phosphorus and genistein
      concentrations. Serum and bones from half of the animals from each diet group
      were taken at weaning and from the remaining half at 4 weeks post-weaning. Bones
      underwent histomorphometric analysis and serum was used for genistein
      determinations. RESULTS: Serum genistein and milk concentrations reflected
      dietary isoflavone dose. Isoflavone intake had no effect on any of the bone
      changes associated with lactation or recovery. Milk calcium and mineral
      concentrations were unaffected by dietary isoflavones. CONCLUSIONS: Consumption
      of soy isoflavones, in levels that can be readily attained through soy foods,
      have neither protective effects on bone nor deleterious effects on milk quality
      or quantity during lactation.

PMID- 19093162
TI  - Dietary calcium and vitamin D2 supplementation with enhanced Lentinula edodes
      improves osteoporosis-like symptoms and induces duodenal and renal active calcium
      transport gene expression in mice.
AB  - The two main sources of vitamin D3 are de novo synthesis induced by exposure to
      ultraviolet (UV) light from the sun, and diet. Vitamin D3 deficiency causes
      rickets or osteoporosis. Oak mushrooms (Lentinula edodes) that are exposed to UV
      radiation contain enhanced vitamin D2 and have much higher calcium content than
      unmodified (non-irradiated) mushrooms. Such modified edible mushrooms have been
      proposed as a natural alternative source of dietary vitamin D. In the current
      study, we have examined whether modified oak mushrooms could improve or prevent
      osteoporosis-like symptoms in mice fed with low calcium and vitamin D3-deficient
      diet. Four-week-old male mice were fed low calcium, vitamin D3-deficient diets
      supplemented with 5, 10, or 20% unmodified, calcium-enhanced, or calcium plus
      vitamin D2-enhanced oak mushrooms for 4 weeks. To assess the effects of the
      supplemented diets, we evaluated femur density and length, bone histology, the
      expression of active calcium transport genes, and serum calcium levels. Mice fed
      with low calcium and vitamin D3-deficient diet developed osteoporosis-like
      symptoms within 4 weeks. Femur density and tibia thickness were significantly
      higher in mice fed calcium plus vitamin D2-enhanced mushrooms, and the expression
      of duodenal and renal calcium transport genes was significantly induced. These
      results indicate that in mice, vitamin D2 and/or calcium derived from irradiated
      oak mushrooms may improve bone mineralization through a direct effect on the
      bone, and by inducing the expression of calcium-absorbing genes in the duodenum
      and kidney.

PMID- 19093163
TI  - Valproic acid exerts anti-tumor as well as anti-angiogenic effects on myeloma.
AB  - Multiple myeloma is still an incurable disease, most commonly occurring in the
      elderly. The myeloma-induced bone marrow microenvironment protects myeloma cells
      from drug-induced apoptosis. Therefore, the development of novel and tolerable
      therapeutic alternatives to overcome the drug resistance is an important clinical
      issue. Valproic acid (VPA), a safe and widely used anti-epileptic agent, is
      revisited as a class I- and IIa-specific histone deacetylase inhibitor. In the
      present study, we evaluated the effect as well as a mechanism of actions of VPA
      on myeloma cell growth and survival, with special reference to the myeloma
      induced bone marrow microenvironment. VPA at therapeutic concentrations for
      epilepsy induced cell death in primary CD138-positive myeloma cells as well as
      myeloma cell lines, but not in CD138-negative bone marrow cells. VPA suppressed
      osteoclastogenesis as well as osteoclast-mediated myeloma cell growth. VPA also
      inhibited vascular tubule formation enhanced by co-cultures of myeloma cells and
      osteoclasts in concert with thalidomide. In addition, VPA induced both caspase
      dependent and -independent cell death in myeloma cells, and potentiated the anti
      myeloma effects of melphalan and dexamethasone. Collectively, VPA is suggested to
      exert multi-factorial anti-myeloma actions, and may serve as a safe adjuvant to
      be included in conventional chemotherapies against myeloma.

PMID- 19093164
TI  - Leukemic infiltration of the lung following allogeneic hematopoietic stem cell
      transplantation.
AB  - Pulmonary leukemic infiltration (PLI) is more common than generally recognized,
      but accurate antemortem diagnosis with pathological proof is rarely achieved. We
      describe herein the clinical courses of two patients with PLI following
      hematopoietic stem cell transplantation (HSCT). One case is a male patient with
      acute biphenotypic leukemia, and the other is a female patient with
      myelodysplastic syndrome. In both cases, hyperleukocytosis did not proceed to
      PLI. Moreover, the former case presented PLI as the initial manifestation of
      relapsed leukemia and the latter was accompanied with the fungal pneumonia. High
      resolution computed tomography (HRCT) of the chest at onset of PLI showed diffuse
      small nodular lesions along peribronchovascular bundle, and diagnosis of leukemic
      infiltration was made based on pathological findings obtained from transbronchial
      lung biopsy. Biopsy specimens further revealed leukemic infiltration along the
      lymphatic surrounding the peribronchial or perivascluar regions, which
      corresponded well with HRCT findings. Thus, radiological and pathological
      corroborating assessment was important to reach the correct diagnosis.

PMID- 19093165
TI  - Emergence of abnormal clone with monsomy 7 in Philadelphia negative cells of CML
      patients treated with tyrosine kinase inhibitors.

PMID- 19093167
TI  - Comparison of clinicopathologic findings according to JAK2 V617F mutation in
      patients with essential thrombocythemia.
AB  - The JAK2 V617F mutation is present in most patients with polycythemia vera, but
      in fewer patients with essential thrombocythemia (ET). We have assessed the
      frequency of this mutation in ET patients using amplification refractory mutation
      system PCR and determined the relationship of the mutation with disease
      phenotypes. Clinical-laboratory findings and histomorphological features were
      compared according to mutational status in 108 ET patients. The mutation was
      detected in 61 patients (56.5%) including one homozygous patient. Those with the
      mutation had significantly higher leukocyte (P = 0.003) and neutrophil (P =
      0.007) counts. However, the incidences of thrombotic events and progression to
      advanced stages did not differ significantly between patients with and without
      the mutation. Thrombotic events were significantly correlated with older age (P =
      0.025). Morphological analysis revealed that erythroid hypoplasia was exclusively
      found in the mutation-negative patients (P = 0.027). We could confirm previous
      findings of higher leukocyte count in ET patients with JAK2 mutation, but could
      not find any correlation with thrombotic events. Therefore, the detection of the
      mutation could characterize a subset of ET patients with distinct phenotype,
      despite its clinical significance being still undetermined.

PMID- 19093166
TI  - Recent advances in the treatment of Philadelphia chromosome-positive acute
      lymphoblastic leukemia.
AB  - The advent of imatinib, a selective inhibitor of the ABL tyrosine kinase, has
      revolutionized the treatment of Philadelphia chromosome-positive acute
      lymphoblastic leukemia (Ph+ ALL). Combined with chemotherapy, imatinib exerts
      remarkable efficacy in patients with newly diagnosed disease with a complete
      remission (CR) rate of 95% and a survival rate of 55% at 3 years. Profound
      eradication of leukemia cells not only provides patients with a better chance for
      receiving allogeneic hematopoietic stem cell transplantation during first CR but
      also contributes to durable CR even without transplantation. Despite such
      improvement, however, relapse does occur, mainly owing to acquisition of
      resistance. Growing comprehension of the molecular mechanisms of resistance to
      imatinib has led to the development of novel BCR-ABL inhibitors that yield higher
      affinity for BCR-ABL and/or potent inhibitory activity against other target
      molecules such as SRC family kinases. The second-generation ABL kinase
      inhibitors, namely dasatinib and nilotinib, are already showing clinical activity
      in patients with imatinib-resistant Ph+ ALL, and other novel agents are
      undergoing preclinical and early clinical evaluation. Further improvement in
      treatment results will be achieved by identifying each patient's disease profile
      based on information obtained before and during treatment and by optimizing
      subsequent treatment accordingly.

PMID- 19093168
TI  - A case of age-related EBV-associated B-cell lymphoproliferative disorder
      metachronously showing two distinct morphologic appearances, one of a polymorphic
      disease resembling classical Hodgkin lymphoma, and the other of a large-cell
      lymphoma.
AB  - We report a case of age-related EBV-associated B-cell lymphoproliferative
      disorder (age-related EBV+ B-cell LPD) metachronously showing two distinct
      morphologic appearances: one of a polymorphic disease resembling classical
      Hodgkin lymphoma (CHL), and the other of a large-cell lymphoma. A 71-year-old man
      was admitted to the St. Marianna University Hospital because of fever and
      generalized lymphadenopathy. Right axillary lymph node biopsy revealed mixed
      cellularity classical Hodgkin lymphoma (MCHL). The patient was referred to the
      Tokyo Medical Center, where he was treated with chemotherapy and obtained CR. One
      year later, the patient again developed fever and generalized lymphadenopathy.
      Biopsy of the right cervical mass revealed a diagnosis of diffuse large B-cell
      lymphoma. The patient was treated with salvage chemotherapies and obtained the
      second CR. Two years later, the patient developed acute myeloid leukemia (AML).
      Although CR was achieved with chemotherapy, AML relapsed 5 months later and
      proved to be refractory. Two and a half years later, the patient developed right
      cervical lymph node enlargement. The biopsy again revealed diagnosis of MCHL. The
      patient died 2 months later. On reviewing all of the biopsy specimens, including
      the findings of immunohistochemistry and in situ hybridization, possibility of
      CHL was ruled out, because neoplastic giant cells resembling Hodgkin and Reed
      Sternberg (HRS) cells were positive for both Oct2 and BOB.1, which has not been
      reported in CHL. Both HRS-like cells at the time of diagnosis of Hodgkin lymphoma
      and lymphoma cells at the time of diagnosis of non-Hodgkin lymphoma were positive
      for CD20 and EBV-encoded small RNAs. This case was finally diagnosed as having
      age-related EBV+ B-cell LPD. We report the case here as it underscores the
      difficulty in diagnosing age-related EBV+ B-cell LPDs and also suggests an
      important role of EBV in the pathogenesis of lymphoid neoplasms.

PMID- 19093169
TI  - Identification of sentinel lymph node location based on body surface landmarks in
      early breast cancer patients.
AB  - BACKGROUND: It would be extremely useful if the location of the sentinel lymph
      node in breast cancer could be identified based on body surface landmarks.
      However, the identification of the sentinel node location by using surface
      landmarks in many reports is based on empirical methodologies. METHODS: We
      studied the distribution of the sentinel node location in 70 breast cancer
      patients based on the lateral line of the major pectoral muscle, the axillary
      skin fold that divides the trunk and the upper arm, and the nipple of the breast.
      RESULTS: The location of the sentinel node could be predicted using an ellipse
      with a semi-major axis of 2.8 cm and a semi-minor axis of 2.2 cm with a
      probability of 95% for a patient with the mean body size. CONCLUSION: Our data
      demonstrate that the location of the sentinel nodes can be predicted within a
      narrow area based on body landmarks.

PMID- 19093171
TI  - Recent advances in chemotherapy and chemoradiotherapy for gastrointestinal tract
      cancers.

PMID- 19093172
TI  - Neoadjuvant chemoradiation therapy for the treatment of esophageal carcinoma.
AB  - An esophagectomy with three-field lymph node dissection is the standard therapy
      for esophageal cancer in many countries, including Japan. However, the results of
      esophagectomy are still unsatisfactory in comparison to the results of surgical
      treatment for gastric cancer or colon cancer. On the other hand, definitive
      chemoradiation therapy has recently shown progress as a treatment modality for
      resectable esophageal cancer, with data indicating the potential efficacy of
      combination therapy with chemoradiation and an esophagectomy. In fact,
      preoperative chemoradiotherapy for resectable esophageal cancer is becoming a
      standard therapy in Europe and North America. The latest metaanalysis concerning
      neoadjuvant chemoradiotherapy for resectable esophageal cancer concluded that a
      significant survival benefit was evident with preoperative chemoradiotherapy.
      However, there are still no supportive data for neoadjuvant chemoradiation and
      surgery from a well-designed large-scale randomized control trial (RCT). A well
      designed large-scale RCT is needed to determine the utility of neoadjuvant
      chemoradiation. Future trials based on precise diagnosis and surgical procedures
      are required for the adequate interpretation of the results of treatment for
      resectable esophageal cancer. Of course, quality control of the operation is a
      very important factor, because operative mortality influences these results.

PMID- 19093173
TI  - Recent advances in chemotherapy and chemoradiotherapy for gastrointestinal tract
      cancers: adjuvant chemoradiotherapy for gastric cancer.
AB  - Chemoradiotherapy (CRT) is one of the effective modalities for the local control
      of gastric cancer. Advances in CRT as an adjuvant treatment have been made in the
      West. The INT0116 trial demonstrated that postoperative chemotherapy with 5
      fluorouracil (FU) plus leucovorin and concomitant 45-Gy radiation significantly
      improved the survival of gastric cancer patients who received gastrectomy with D0
      or D1 lymph node dissection. As the result of this trial, the standard treatment
      for curable gastric cancer in the United States has been considered as a
      combination of surgery and postoperative CRT. The great interest in CRT in the
      adjuvant setting for gastric cancer has induced oncologists, particularly in the
      West, to conduct new clinical trials using various kinds of anticancer drugs.
      However, there is no rationale for adjuvant CRT after D2 dissection. Large-scale
      randomized controlled trials in Japanese patients have shown significant
      improvement of overall survival brought about by postoperative adjuvant
      chemotherapy with S-1. The results of these studies have suggested that even D2
      surgery alone brings about much better survival for patients than limited surgery
      plus adjuvant CRT. Thus, strategies for the postoperative treatment of gastric
      cancers should be classified according to the degree of surgery.

PMID- 19093174
TI  - Chemotherapy for metastatic gastric cancer in Japan.
AB  - Until the 1990s, there were no chemotherapy regimens with old-generation
      anticancer agents showing a survival benefit over 5-fluorouracil (FU) alone, and
      standard chemotherapy for metastatic gastric cancer had not been established. In
      the late 1990s, several new active agents were developed and some phase III
      trials with these agents were conducted; the new agent S-1 showed noninferiority
      to 5-FU in these trials. S-1 plus cisplatin is the first doublet chemotherapy to
      have shown a survival benefit over monotherapy with S-1. It has been demonstrated
      that capecitabine and oxaliplatin (OHP) can replace 5-FU and cisplatin (CDDP),
      offering more convenient treatment options. Thus, combination chemotherapy with
      an oral fluoropyrimidine (S-1 or capecitabine) and platinum (CDDP or OHP) has
      been recognized as standard chemotherapy for metastatic gastric cancer all over
      the world. However, it can be said that none of these new combination
      chemotherapies have shown remarkable progress from 5-FU plus cisplatin regimens.
      It is expected that triplet chemotherapy with a taxane; the use of molecular
      targeting agents; and the establishment of treatment strategies including second
      line chemotherapy, will lead to remarkable progress in personalized medicine in
      the near future.

PMID- 19093175
TI  - Chemoradiotherapy and adjuvant chemotherapy for rectal cancer.
AB  - Local recurrence is an important factor in determining the outcome of patients
      after surgery for rectal cancer, and various attempts have been made to reduce
      the local recurrence rate. Randomized controlled trials have shown that
      radiotherapy combined with total mesorectal excision can reduce the local
      recurrence rate in rectal cancer patients who undergo curative surgery.
      Chemoradiotherapy is more effective in achieving local control than radiotherapy
      alone, and preoperative chemoradiotherapy is superior to postoperative
      chemoradiotherapy in terms of adverse events. Recent advances have led to the
      identification of potential therapeutic targets such as epidermal growth factor
      receptor, vascular endothelial growth factor, and endothelial receptors. These
      new agents have been used in combination with conventional chemoradiotherapy, and
      higher pathological complete response rates have been reported for such
      combinations in comparison with conventional regimens. With regard to lateral
      node dissection, a recent study showed that postoperative chemoradiotherapy was
      more effective in reducing the local recurrence rate than lateral node
      dissection. As for adjuvant chemotherapy, one randomized controlled trial showed
      that patients who received uracil and tegafur as adjuvant therapy had
      significantly prolonged relapse-free survival times and overall survival times.
      As well, one metaanalysis has shown the efficacy of oral uracil-tegafur as
      adjuvant chemotherapy for rectal cancer.

PMID- 19093176
TI  - Predicting clinical outcome of 5-fluorouracil-based chemotherapy for colon cancer
      patients: is the CpG island methylator phenotype the 5-fluorouracil-responsive
      subgroup?
AB  - The CpG island methylator phenotype (CIMP+) of colorectal cancer (CRC) occurs
      predominantly in the proximal colon and is characterized by frequent
      hypermethylation of gene promoter regions. In this review, we present evidence
      suggesting CIMP+ represents the subgroup of colon cancers that are responsive to
      5-fluorouracil (5-FU)-based treatments. CIMP+ has been associated with survival
      benefit from 5-FU in a clinical study of CRC, with additional evidence coming
      from studies on gastric cancer and tumor cell lines. Elevated concentrations of 5
      10-methylene tetrahydrofolate (CH(2)FH(4)) occur in CIMP+ tumors and are probably
      due to low expression levels for gamma-glutamyl hydrolase (GGH). Clinical and in
      vitro work has previously shown that high CH(2)FH(4) and low GGH expression
      levels correlate with good response to 5-FU. Methylation-induced silencing of
      dihydropyrimidine dehydrogenase, the rate-limiting enzyme in 5-FU degradation,
      may also provide a link between CIMP+ and good response to 5-FU. The CIMP+
      related phenotype referred to as microsatellite instability (MSI+) has been
      widely investigated as a predictive marker of response to 5-FU, with
      contradictory results. The interpretation of these studies is likely to be
      confounded by the fact that some MSI+ tumors occur in the background of CIMP+,
      but a significant proportion of others do not. Further studies on tumors from
      randomized clinical trials are required to confirm the value of CIMP+ and
      associated molecular features for the prediction of clinical outcome to 5-FU
      based chemotherapy.

PMID- 19093177
TI  - Contemporary management of muscle-invasive bladder cancer.
AB  - Over the past decade, there have been a number of substantial changes in the
      treatment of invasive bladder cancer. Muscle-invasive bladder cancer is an
      aggressive disease that often presents at an advanced stage with or without
      distant metastases. The potential for cure is highest when the disease is
      confined to the bladder. Optimal management depends on our understanding of
      disease biology, refinements to our clinical staging, and improvements in the
      quality of treatment. This review will focus on the contemporary management of
      muscle-invasive urothelial carcinoma of the bladder and will discuss the role of
      radical cystectomy, extended lymphadenectomy, neoadjuvant/ adjuvant chemotherapy,
      and various forms of bladder-preservation strategies.

PMID- 19093178
TI  - Gemcitabine and paclitaxel chemotherapy for advanced urothelial carcinoma in
      patients who have received prior cisplatin-based chemotherapy.
AB  - BACKGROUND: The objective of this study was to evaluate the efficacy and toxicity
      of combination chemotherapy with gemcitabine and paclitaxel as a second-line
      regimen in patients with advanced urothelial carcinoma. METHODS: Twenty patients
      with advanced urothelial carcinoma who were resistant to an M-VAC (methotrexate,
      vinblastine, doxorubicin, and cisplatin) chemotherapy regimen were administered
      chemotherapy consisting of intravenous gemcitabine 2500 mg/m(2) and paclitaxel
      150 mg/m(2) (GP) every 2 or 3 weeks. RESULTS: The patients received a median of
      7.7 cycles of treatment (range, 2-20 cycles). Six of the 20 patients (30%; 95%
      confidence interval [CI], 10%-50%) had a major response to treatment (a complete
      response [CR] in 5% and a partial response [PR] in 25%). Seven patients (35%) had
      stable disease (SD). The median duration of response was 4.5 months (range, 1-9
      months) and the disease control rate (CR + PR + SD) was 65%. The median survival
      was 11.5 months (range, 2-22 months) and the 1-year survival rate was 35%. The
      patients tolerated this regimen well, with only grade 3-4 neutropenia being
      observed in 6 patients (30%), anemia in 3 (15%), and thrombocytopenia in 1 (5%).
      The response rate to M-VAC in the first-line chemotherapy was significantly
      associated with the response to GP as the second-line chemotherapy. CONCLUSION:
      The combination of gemcitabine and paclitaxel is active and well tolerated as a
      second-line treatment in patients with advanced urothelial carcinoma.

PMID- 19093179
TI  - Comparison of alternate-day versus consecutive-day treatment with S-1: assessment
      of tumor growth inhibition and toxicity reduction in gastric cancer cell lines in
      vitro and in vivo.
AB  - BACKGROUND: The toxic effects of S-1 can lead to discontinuation of treatment.
      Strategies for reducing toxicity without compromising therapeutic effectiveness
      are required. METHODS: We used the human gastric cancer cell lines MKN28 and
      MKN45 to examine such strategies in vitro. The cell lines were treated with three
      different regimens, given on alternate days (alternate-day) or on consecutive
      days (consecutive-day). On consecutive days, treatment A provided the same total
      dose as the alternate-day treatment, and treatment B was given for the same
      number of days as the alternate-day treatment. A fourth group served as control.
      In vitro, the relative inhibition (RI) of tumor growth by 5-fluorouracil was
      calculated using the 2-(2-methyl-4-nitrophenyl)-3-(4-nitrophyl)-5-2, 4
      disulfophenyl)-2H-tetrazolium (WST-8) method. We also carried out an in vivo
      experiment in which tumor-bearing nude mice (BALBc/nu-nu) were used to examine
      the antitumor activity of S-1. Leukocyte counts and gastrointestinal mucosal
      injury were compared in mice that received alternate-day and consecutive-day
      treatments. RESULTS: In vitro, for MKN28, the RI was 22.9% for alternate-day,
      34.1% for consecutive-day A, and 37.7% for consecutive-day B treatments. For
      MKN45, the RI was 51.1% for alternate-day, 52.2% for consecutive-day A, and 50.5%
      for consecutive-day B treatments. In vivo, for MKN28, the treated groups showed
      higher inhibition than the control, and inhibition of tumor growth was higher
      with alternate-day than with consecutive-day treatment. The RI was significantly
      higher with alternate-day (49.3%) than with consecutive-day treatment (16.2%; P <
      0.05). For MKN45, the RI was greater than 50% in both treated groups. With
      consecutive-day treatment, 5 of the 14 mice used died during treatment. Leukocyte
      counts were lower in the mice with consecutive-day than with alternate-day
      treatment, or control. Atrophic changes and inflammatory cell infiltration of the
      small intestinal mucosa were severe after consecutive-day, but minimal after
      alternate-day treatment. CONCLUSION: Experimentally, alternate-day treatment with
      S-1 is equivalent to consecutive-day treatment in terms of RI of tumor growth,
      with lower toxicity.

PMID- 19093180
TI  - Surgical complications of salvage total laryngectomy following concurrent
      chemoradiotherapy.
AB  - BACKGROUND: Surgical complication rates of total laryngectomy vary according to
      the preoperative treatments performed and patient factors. Wound complications
      after salvage laryngectomy following concurrent chemoradiotherapy (CCRT) were
      analyzed. METHODS: Eighty-six patients who had undergone total laryngectomy for
      laryngeal cancer at Hokkaido University Hospital, Japan, between 1990 and 2006
      were divided into three groups according to preoperative treatments received:
      group I (n = 35) without radiotherapy (RT) or CCRT, group II (n = 17) RT alone,
      and group III (n = 34) low-dose CCRT. Salvage total laryngectomy was performed as
      a consequence of residual or recurrent disease after completion of the
      treatments. Wound complications such as pharyngocutaneous fistulas, bleeding,
      infections, and skin necrosis were retrospectively analyzed in each group.
      RESULTS: A considerable (not statistically significant) difference in the
      incidence of major wound complications was observed between groups I and III
      (11.4% vs 29.4%, P = 0.078), but not between groups II and III. In stage III/IV
      patients, a significant increase in the incidence of wound complications was
      observed in group III compared to group I. Pharyngocutaneous fistulas were the
      most common complication, occurring in 8/34 (23.5%) of the group III patients.
      Additional pharyngeal reconstruction surgery was performed in 5 of the 8 (62.5%)
      group III patients with pha ryngocutaneous fistulas, while no such patients (0/3)
      in group I required reconstruction surgery. CONCLUSION: There was an increased
      risk of wound complications in patients undergoing salvage laryngectomy following
      CCRT. Patients who developed pharyngocutaneous fistulas after CCRT tended to
      require surgical reintervention for repair. These findings should be taken into
      account before the initiation of CCRT and salvage surgery.

PMID- 19093181
TI  - Prognostic value of CD57(+) T lymphocytes in the peripheral blood of patients
      with advanced gastric cancer.
AB  - BACKGROUND: Natural killer (NK)-like T cells comprising CD56(+) T cells and
      CD57(+) T cells belong to a subset of CD1d-independent NKT cells playing an
      important role in regulating immune responses. Although NK-like T cells are
      reported to increase in patients with advanced gastric carcinomas, it remains
      unknown how NK-like T cells are involved in disease progression in gastric cancer
      patients. METHODS: The proportions of Th1 cells (interferon [IFN]-gamma-producing
      CD4(+) T cells), Th2 cells (IL-4-producing CD4(+) T cells), and NK-like T cells
      (CD56(+) T cells and CD57(+) T cells) in the peripheral blood of 48 gastric
      cancer patients and 20 healthy controls were measured by two-color flow cytometry
      analysis and by intracellular cytokine analysis to investigate an association of
      these immune cells with the survival rate of gastric cancer patients. RESULTS:
      Univariate analysis showed that Th1 cells and CD57(+) T cells, as well as some
      clinicopathological factors, significantly influenced the survival rate. CD57
      high (> or ==18%) patients survived for a significantly shorter period after
      surgery compared to CD57-low patients (P = 0.046; Kaplan-Meier, log-rank test) in
      the stage III-IV patients, but not in the stage I-II patients. Further,
      multivariate analysis showed that lymphatic invasion was a statistically
      significant independent risk factor in all the gastric cancer patients, but the
      proportion of CD57(+) T cells as well as depth of tumor were statistically
      significant independent risk factors in patients with advanced carcinomas (stage
      III-IV). CONCLUSION: An increased proportion (> or ==18%) of CD57(+) T cells in
      the peripheral blood of patients with advanced gastric carcinomas could indicate
      a poor prognosis.

PMID- 19093183
TI  - Glassy cell carcinoma of the uterine cervix responsive to neoadjuvant
      intraarterial chemotherapy.
AB  - Described as a poorly differentiated adenosquamous cancer, glassy cell carcinoma
      of the uterine cervix is a rare disease considered to have an extremely poor
      prognosis. Saitama Medical Center has been offering neoadjuvant intraarterial
      chemotherapy (NAC) to cervical cancer patients as a means of avoiding
      postoperative radiation therapy, achieving downstaging, and improving prognosis.
      We report a patient with glassy cell carcinoma of the uterine cervix who
      responded to NAC, and we discuss this case with reference to reports in the
      literature. A 28-year-old gravida 1, para 0 patient was referred to the
      Department of Obstetrics and Gynecology at Saitama Medical Center for concurrent
      cervical cancer at 23.5 gestational weeks. The patient was admitted to our center
      following the diagnosis of stage IIb cervical cancer (glassy cell carcinoma), to
      await fetal development, and an elective cesarean section was performed at
      slightly more than 29 gestational weeks. Three cycles of NAC with carboplatin
      (CBDCA)/etoposide/epirubicin, started 3 days after the operation, shrank the
      tumor remarkably. An extended radical hysterectomy was subsequently performed. It
      has been 6 years, to date, since the initial treatment, and our patient is alive
      and disease/recurrence free.

PMID- 19093182
TI  - Pilot study of intraperitoneal administration of paclitaxel and oral S-1 for
      patients with peritoneal metastasis due to advanced gastric cancer.
AB  - BACKGROUND: There is no standard treatment for peritoneal dissemination from
      gastric cancer. A novel combination chemotherapy has been introduced for patients
      with advanced gastric cancer with peritoneal metastasis. METHODS: This pilot
      study was performed on four patients to confirm safety and efficacy. They were
      diagnosed with unresectable gastric cancer with severe peritoneal dissemination
      by staging laparoscopy, or with metastasis to the transverse colon. We selected
      combined chemotherapy with both paclitaxel and S-1. Paclitaxel at 60 mg/m(2) or
      60 mg/body was administered intraperitoneally on days 1 and 8 and S-1, at 80-120
      mg/body, was administered orally for 14 days followed by 7 days' rest, as one
      course. After five courses of this therapy, the primary gastric tumors were
      evaluated by conventional examinations, and second-look laparoscopy was performed
      to assess the efficacy of the treatment against the peritoneal metastases.
      RESULTS: After five courses, primary tumor reductions were confirmed, and no
      cancer cells were detected on pathocytological investigation during second-look
      laparoscopy in any of the patients. Three patients underwent total gastrectomy
      with lymph node dissection and one underwent left upper abdominal evisceration.
      Final histological staging showed two stage 3 and two stage 4 patients. The
      intraperitoneal administration of paclitaxel and the oral administration of S-1
      were well tolerated. Three patients died, at 8, 15, and 29 months, respectively,
      after the initial treatment, and one has been alive for 54 months without
      recurrence. CONCLUSION: This chemotherapy can be used in the treatment of
      patients with peritoneal metastasis of gastric cancer.

PMID- 19093184
TI  - Successful treatment of advanced gallbladder cancer with an anticancer drug S-1:
      assessment based on intratumoral gene.
AB  - While surgical resection is the most effective treatment for gallbladder cancer,
      most of these cancers are not resectable at the time of diagnosis, and therefore,
      chemotherapy serves as the primary therapy in many cases. However, to date, there
      is no standard chemotherapy for this cancer. We report a case of advanced
      gallbladder cancer for which the anticancer drug S-1 was effective. The patient
      was a 53-year-old woman who presented with a huge ovarian tumor. On workup, all
      abdominal images revealed the presence of advanced gallbladder cancer that had
      invaded the liver. Because the gallbladder formed a relatively hard and swollen
      mass involving the omentum, as revealed during exploration, the surgical
      resection of the gallbladder was not possible at that time, and only hysterectomy
      and bilateral salpingo-oophorectomy were performed. She started on the anticancer
      drug S-1 just after this operation. S-1 is a prodrug of 5-fluorouracil (5-FU),
      and contains 5-chloro-2-4-dihydroxypyridine (CDHP), an inhibitor of
      dihydropyrimidine dehydrogenase (DPD) that rapidly degrades 5-FU. Eight months
      after the first operation, radical cholecystectomy was performed. Pathologically,
      the tumor was diagnosed as an adenocarcinoma of the gallbladder, and no evidence
      of liver invasion was found. Intratumoral gene expression analysis of the
      resected gallbladder revealed significantly elevated DPD expression. We suggest
      that the rapid degradation of 5-FU mediated by this high DPD in our patient was
      significantly blocked by the CDHP in S-1, and that the efficacy of 5-FU was
      consequently maintained at the maximum level.

PMID- 19093185
TI  - Clear-cell adenocarcinoma of the uterine cervix in a 17-year-old adolescent.
AB  - This report describes the case of the youngest Japanese person to be diagnosed
      with endocervical clearcell adenocarcinoma. In September 2005, a 17-year-old
      female adolescent visited a physician because of vaginal bleeding. A cervical
      tumor was discovered, and the patient was referred to our outpatient department.
      Vaginal examination showed a bleeding tumor approximately 1.5 cm in size
      protruding from the cervical os. The cytological finding of the uterine cervix
      was positive for malignancy, and the histological diagnosis by punch biopsy was
      clear-cell adenocarcinoma of the uterine cervix. A radical abdominal hysterectomy
      and pelvic lymphadenectomy were performed on October 30. Macroscopic findings
      showed a tumor, 1.5 cm in diameter, growing from the right side of the uterine
      cervix. The pathological diagnosis was clear-cell adenocarcinoma of the cervix
      (PT1b1NR0M0). The patient was discharged from our hospital without any adjuvant
      therapy. No signs of recurrence have been detected in the 2-year follow up.

PMID- 19093186
TI  - Leptomeningeal metastasis from ovarian carcinoma successfully treated by the
      intraventricular administration of methotrexate.
AB  - A 60-year-old woman with a history of ovarian carcinoma and complaining of gait
      instability, dizziness, nausea, and a right temporal headache visited a
      neurologist. A diagnosis of leptomeningeal metastasis was made, based on the
      results of a cerebrospinal fluid examination. After the administration of
      intrathecal methotrexate, her neurological complaints disappeared. An Ommaya
      intraventricular reservoir was inserted, and methotrexate administration was
      continued for 11 months, until another recurrence was found in her pelvis.
      Although uncommon, the possibility of leptomeningeal metastasis from ovarian
      carcinoma should be considered; in such cases, treatment with intraventricular
      methotrexate may be effective and feasible and should be considered as a
      treatment strategy.

PMID- 19093187
TI  - Muir-Torre syndrome associated with endometrial carcinoma.
AB  - Muir-Torre syndrome (MTS) is an autosomaldominant skin condition of genetic
      origin, characterized by tumors of the sebaceous glands or keratoacanthomas that
      are associated with malignant visceral diseases. MTS associated with gynecologic
      malignancy has rarely been reported. Here we report a woman with no family
      history of colorectal cancer who developed endometrial carcinoma, stage 3a, at 49
      years of age and at age 51 years, developed two skin tumors, a nasal squamous
      cell carcinoma and a sebaceous carcinoma of the right eyelid. The appearance
      pattern of these skin tumors suggested MTS. Although MTS associated with
      endometrial carcinoma is rare, patients with endometrial carcinoma should undergo
      evaluation for visceral malignancies (mainly colon cancer) and sebaceous skin
      lesions, regardless of whether or not there is a family history of colorectal
      cancer.

PMID- 19093188
TI  - Hepatocellular carcinoma (HCC) recurring 10 years after clearance of hepatitis B
      surface antigen and 20 years after resection of hepatitis B virus-related HCC.
AB  - A 62-year-old man had been followed up for chronic hepatitis B (HB) since 1973.
      Hepatocellular carcinoma (HCC) was detected in 1985, at the age of 42 years.
      Serum HB surface antigen and anti-HB envelope antibody were positive at that
      time. A right hepatic lobectomy was performed. In 1995, serum HB surface antigen
      had cleared spontaneously and liver function had normalized. In March 2005, at
      the age of 62 years, a 1.5-cm diameter hepatic mass was detected in the left
      lateral segment. At that time, he was seropositive only for anti-HB core
      antibody. A diagnosis of recurrent HCC was made, and partial hepatectomy was
      performed. Covalently closed circular HBV DNA was detected in both cancerous and
      noncancerous tissues by nested polymerase chain reaction (PCR). Cassette-ligation
      mediated PCR showed that HBV DNA was integrated into the telomerase reverse
      transcriptase gene located on chromosome 5p15.

PMID- 19093189
TI  - Long-term complete response of multiple hepatic metastases from carcinoma of the
      papilla of Vater using intrahepatic infusion of 5-FU with low-dose cisplatin
      following pancreaticoduodenectomy.
AB  - Of all distant metastases from carcinoma of the papilla of Vater (CPV), the liver
      is the most frequent site (more than 60%) and should be specifically targeted in
      the effort to improve the prognosis. However, the optimal chemotherapy regimen
      for nonresectable liver metastasis has not been clearly established. In this
      preliminary report, we note a patient with multiple hepatic metastases from CPV
      successfully treated using intrahepatic infusion of 5-fluorouracil (FU) with low
      dose cisplatin. A 62-year-old woman underwent curative pylorus-preserving
      pancreaticoduodenectomy for CPV. Four months after surgery, followup computed
      tomography (CT) demonstrated multiple liver metastases. Weekly intrahepatic
      arterial infusion chemotherapy of 5-FU, 350 mg/m(2), with low-dose cisplatin (7
      mg/m(2)) was started. Ten months after starting chemotherapy, a complete response
      was obtained. To date, the patient continues to receive this weekly hepatic
      arterial infusion chemotherapy without any side effects, and she has successfully
      maintained a long-term complete response for 20 months. The patient remains well
      and was able to proceed with daily activity at the last follow up 30 months after
      starting this chemotherapy regimen. This regimen is safe and effective and is
      recommended as one of the treatment choices for liver metastases from CPV.

PMID- 19093191
TI  - ERP correlates of error monitoring in adult ADHD.
AB  - The purpose of the current study was to evaluate whether error monitoring
      difficulties persist in adults with attention deficit hyperactivity disorder
      (ADHD) using the event-related potential (ERP) methodology. Adults with ADHD and
      age-matched healthy controls executed a visual Go/No-Go task with 25% No-Go
      trials. Performance and ERP correlates of error monitoring were compared between
      groups. At the performance level no difference was noted between groups. However,
      exploring the error-related potentials revealed that the error-related negativity
      (ERN) was the same for both groups, but that adults with ADHD showed a smaller
      error positivity (Pe). Based on these findings, we conclude that adults with ADHD
      are normal in early automatic error detection, but are deviant in later conscious
      evaluation of the error. The findings add to the increasing evidence supporting
      disturbances in error monitoring in ADHD and show that these problems may persist
      in adulthood ADHD.

PMID- 19093192
TI  - Plant growth, metabolism and adaptation in relation to stress conditions. XXVII.
      Can ascorbic acid modify the adverse effects of NaCl and mannitol on amino acids,
      nucleic acids and protein patterns in Vicia faba seedlings?
AB  - The adverse effects of either NaCl or mannitol on amino acids, protein patterns
      and nucleic acids in Vicia faba seeds were investigated. The exogenous addition
      of 4 mM ascorbic acid to the stressing media in which the broad bean seeds were
      germinated in combination with either the ionic (NaCl) or osmotic (mannitol)
      stressor induced significant protective changes in the total amount and in the
      relative composition of amino acids in general and in proline, glycine, glutamic,
      aspartic, alanine and serine in particular. It also induced changes in nucleic
      acids (RNA and DNA) content. These changes occurred throughout the entire period
      of the experiments (12 days). Separate administration of NaCl or mannitol
      enhanced the occurrence of particular novel proteins that were not detected in
      control bean seeds (water medium). Protein banding patterns of broad bean
      seedlings treated with NaCl or mannitol in combination with 4 mM ascorbic acid
      showed different de novo protein bands, with different molecular weights, at
      different stages of seedlings growth, with lower levels or a nearly complete
      absence of the major stress proteins. The pattern of changes for amino acids and
      nucleic acids and the range of protein bands extracted from the variously treated
      broad bean seedlings indicate a positive role of ascorbic acid in the alleviation
      of the damage effects induced by NaCl and mannitol. The importance of this role
      in the stress tolerance of broad beans is discussed.

PMID- 19093194
TI  - Determination of aflatoxin M(1) in breast milk samples in Tabriz-Iran.
AB  - The aim of this study was to examine the exposure of lactating mothers to
      aflatoxins using aflatoxin M(1) in breast milk as a biomarker for exposure and to
      detect its determining factors and possible effects on child growth. A 9% sample
      of 2022 lactating women who exclusively breastfed their infants, including 91
      lactating women of urban areas of Tabriz city and 91 lactating women of its rural
      areas were recruited by a geographical clustered sampling method. Breast milk
      samples and information on food intake were collected from subjects using
      structured food-frequency questionnaire. Extraction of AFM(1) was performed with
      the ELISA test procedure. Aflatoxin M(1) was detected in breast milk of 20 out of
      91 mothers (22%) in concentrations of 6.96 +/- 0.94 (pg/ml) in rural areas.
      Aflatoxin M(1) contamination was not present in samples of urban areas. The
      presence of aflatoxin M(1) was significantly associated with consumption of local
      milk (beta = 0.71, P < 0.001) and stunted growth in children (beta = -0.31, P <
      0.015). These findings emphasize the need for developing strategies to reduce
      exposure to aflatoxin, possibly involving interventions targeted at reducing
      contamination of foods.

PMID- 19093193
TI  - TecoflexTM functionalization by curdlan and its effect on protein adsorption and
      bacterial and tissue cell adhesion.
AB  - Curdlan modified polyurethane was created by physically entrapping the former on
      TecoflexTM surface. ATR-FT-IR, SEM-EDAX and AFM analysis revealed the formation
      of stable thin curdlan layer on the film. Contact-angle measurements showed that
      the modified film was highly hydrophilic. Confocal laser scanning microscopy
      showed the existence of entrapped layer of approximately 20-25 microm in depth.
      Surface entrapment of curdlan minimized both protein adsorption and mouse L929
      fibroblast cell adhesion relative to the control. Surface induced cellular
      inflammatory response was determined from the expression levels of
      proinflammatory cytokine TNF-alpha, by measuring their mRNA profiles in the cells
      using real time polymerase chain reaction (RT-PCR) normalized to the housekeeping
      gene GAPDH. The inflammatory response was suppressed on the modified substrate as
      expression of TNF-alpha mRNA was found to be up regulated on TecoflexTM, while it
      was significantly lower on curdlan substrate. The adhesion of S. aureus decreased
      by 62% on curdlan modified surface. Using such simple surface entrapment process,
      it will be possible to develop well-defined surface modifications that promote
      specific cell interactions and perhaps better performance in the long-term as
      implant.

PMID- 19093196
TI  - Anatomic autoandrophilia in an adult male.
AB  - Some men are sexually aroused by impersonating the individuals to whom they are
      sexually attracted, or by permanently changing their bodies to become facsimiles
      of such individuals. Blanchard (J Sex Marital Ther 17:235-251, 1991) suggested
      that these paraphilic sexual interests, along with fetishism, represented erotic
      target location errors, i.e., developmental errors in locating erotic targets in
      the environment. Because the desire to impersonate or become a facsimile of the
      kind of person to whom one is attracted can have significant implications for
      identity, Freund and Blanchard (Br J Psychiatry 162:558-563, 1993) coined the
      term erotic target identity inversion to describe this type of erotic target
      location error. The best-known examples of erotic target identity inversions
      occur in men who are sexually attracted to women and who are also sexually
      aroused by the idea of impersonating or becoming women; these paraphilic
      interests manifest as transvestic fetishism and as one type of male-to-female
      transsexualism. Analogous erotic target identity inversions have been described
      in men who are sexually attracted to children and to female amputees. In theory,
      erotic target identity inversions should also occur in men who are sexually
      attracted to men. There have been no unambiguous descriptions, however, of men
      who are sexually attracted to men and also sexually aroused by the idea of
      changing their bodies to become more sexually attractive men. This report
      describes such a man, whose paraphilic interest would appropriately be called
      anatomic autoandrophilia. The demonstration that anatomic autoandrophilia exists
      in men is consistent with the theory that erotic target location errors
      constitute an independent paraphilic dimension.

PMID- 19093195
TI  - A kinetic model unifying presynaptic short-term facilitation and depression.
AB  - Short-term facilitation and depression refer to the increase and decrease of
      synaptic strength under repetitive stimuli within a timescale of milliseconds to
      seconds. This phenomenon has been attributed to primarily presynaptic mechanisms
      such as calcium-dependent transmitter release and presynaptic vesicle depletion.
      Previous modeling studies that aimed to integrate the complex short-term
      facilitation and short-term depression data derived from varying synapses have
      relied on computer simulation or abstract mathematical approaches. Here, we
      propose a unified theory of synaptic short-term plasticity based on realistic yet
      tractable and testable model descriptions of the underlying intracellular
      biochemical processes. Analysis of the model equations leads to a closed-form
      solution of the resonance frequency, a function of several critical biophysical
      parameters, as the single key indicator of the propensity for synaptic
      facilitation or depression under repetitive stimuli. This integrative model is
      supported by a broad range of transient and frequency response experimental data
      including those from facilitating, depressing or mixed-mode synapses.
      Specifically, the theory predicts that high calcium initial concentration and
      large gain of calcium action result in low resonance frequency and hence
      depressing behavior. In contrast, for synapses that are less sensitive to calcium
      or have higher recovery rate, resonance frequency becomes higher and thus
      facilitation prevails. The notion of resonance frequency therefore allows
      valuable quantitative parametric assessment of the contributions of various
      presynaptic mechanisms to the directionality of synaptic short-term plasticity.
      Thus, the model provides the reasons behind the switching behavior between
      facilitation and depression observed in experiments. New experiments are also
      suggested to control the short-term synaptic signal processing through adjusting
      the resonance frequency and bandwidth.

PMID- 19093197
TI  - Sexual milestones and factors associated with coitus initiation among Israeli
      high school students.
AB  - In view of the developmental approach to sexual behavior, this article presents
      the stages of sexual behavior leading to coitus in four grades of high school
      students in Israel and the sociodemographic factors associated with initiating
      coitus. Analyses were based on data from the first national study dealing
      comprehensively with sexuality in 30 years. A self-administered questionnaire was
      completed by a random sample of 4,609 students of the General Educational
      (secular) system that included 68% of the Hebrew-speaking sector or 55% of all
      students in Israel. Our findings indicated a progressive set of stages of sexual
      behavior forming a Guttman scale, from kissing and petting over the clothes
      though petting under the clothes and genital touching to coitus. In comparison to
      results of a 1970 Israeli survey, we found an increase in practice in all Guttman
      scale stages of sexual behavior, as well as a diminished gap between genders. The
      gap fully disappeared in the three lower stages. Predictive variables of coitus
      initiation included gender, religiosity, immigration status, family structure,
      perceptions of academic achievements, and the proportion of peers practicing
      coitus. In addition to gender, perception of the proportion of peers that already
      practiced intercourse was the best predictor followed by grade, perception of
      academic achievement, and family structure. Marked differences were noticed
      between genders regarding associations with religiosity and immigration status.
      The discussion focused on comparisons to findings in other countries, the
      contribution of the findings to the understanding of Israeli adolescents' sexual
      behavior, and practical educational implications.

PMID- 19093198
TI  - Effects of 3,4-dichloroaniline and diazinon on different biological organisation
      levels of zebrafish (Danio rerio) embryos and larvae.
AB  - In this study the effects of 3,4-dichloroaniline (3,4-DCA), a decomposition
      product of the herbicides propanil and diuron (and other pesticides), and
      diazinon, a neurotoxic insecticide, on early life stages of zebrafish Danio rerio
      were assessed. The toxicity of these substances with different modes of action
      (acetylcholine esterase inhibitor vs. polar narcosis) was tested for single
      substances as well as in binary mixtures. To study effects on different
      biological organisation levels (from the molecular up to the whole organism
      level) the molecular stress response regarding Hsp70, the embryonic and larval
      development and the locomotor activity were investigated as integrative
      biomarkers. In single substance tests 3,4-dichloroaniline elicited deformations
      at > or = 0.25 mg/l during the 11 days subchronic test, whereas locomotor
      activity and mortality were impaired at > or = 0.5 mg/l. Diazinon effects on
      those parameters were obvious at > or = 2 mg/l, except for the deformation rate
      (11 days:1 mg/l). In equitoxic mixtures of both substances concentration
      additivity was observed for deformation rate and mortality (11 days). An increase
      in the Hsp70 content occurred in zebrafish exposed to 0.25 mg 3,4-DCA/l as well
      as to 0.05 mg diazinon/l; in mixtures concentration additivity could be shown.
      The investigated endpoints varied in respect to their sensitivity, with
      deformations and Hsp70 levels as most sensitive parameters concerning 3,4-DCA and
      Hsp70 as most sensitive parameter concerning diazinon. Accordingly, for an
      integrated understanding of the effects of chemicals and their mixtures on fish,
      a battery of different test methods should be applied.

PMID- 19093199
TI  - Time from positive screening fecal occult blood test to colonoscopy and risk of
      neoplasia.
AB  - There is no guideline defining the optimal time from a positive screening fecal
      occult blood test to follow-up colonoscopy. We reviewed records of 231
      consecutive primary care patients who received a colonoscopy within 18 months of
      a positive fecal occult blood test. We examined the relationship between time to
      colonoscopy and risk of neoplasia on colonoscopy using a logistic regression
      analysis adjusting for potential confounders such as age, race, and gender. The
      mean time to colonoscopy was 236 days. Longer time to colonoscopy (OR = 1.10, P =
      0.01) and older age (OR 1.04, P = 0.01) were associated with higher odds of
      neoplasia. The association of time with advanced neoplasia was positive, but not
      statistically significant (OR 1.07, P = 0.14). In this study, a longer interval
      to colonoscopy after fecal occult blood test was associated with an increased
      risk of neoplasia. Determining the optimal interval for follow-up is desirable
      and will require larger studies.

PMID- 19093200
TI  - Z-LLY-FMK attenuates intestinal apoptosis after bile duct ligation in rats.
AB  - Apoptosis is an important process in a wide variety of different biological
      systems. In addition to caspases, recently, calpains, another family of
      proteases, have been found to be involved in apoptosis of many cell systems. This
      study is designed with the aims to evaluate the possible effect of Z-LLY-FMK (a
      calpain inhibitor) on intestine apoptosis after bile duct ligation in rats. Male
      Sprague-Dawley rats weighing 250-300 g were randomized to five groups (n = 6 in
      each group). Group 1 (CONTROL: C) underwent Sham operation and were
      simultaneously treated with the same amount of normal saline. Group 2 (CONTROL
      with DMSO: CDMSO) underwent Sham operation and were simultaneously treated with
      the same amount of dimethylsulfoxide (DMSO). Group 3 (Obstructive jaundice: OB)
      underwent common bile duct ligation without any other manipulation. Group 4
      (Obstructive jaundice with Z-LLY-FMK: OBZLLY) underwent common bile duct ligation
      and were simultaneously treated with Z-LLY-FMK (dissolved in DMSO). Group 5
      (Obstructive jaundice with ZFA-FMK: OBZFA) underwent common bile duct ligation
      and were simultaneously treated with ZFA-FMK (dissolved in DMSO). After 3 days,
      intestine tissue was harvested for apoptosis measurements. There was no
      significant difference between Sham operation group (C) and Sham operation with
      DMSO group (CDMSO) either in jejunum (P = 0.924) or in ileum (P = 0.996). When
      compared to Sham operation group (C), increased intestine apoptosis occurred in
      either jejunum (P < 0.001) or in ileum (P < 0.001) after common bile duct
      ligation (OB). After administration of Z-LLY-FMK (OBZLLY), the increased
      intestine apoptosis after common bile duct ligation (OB) was significantly
      diminished either in jejunum or in ileum (P < 0.001 and P < 0.001). Moreover,
      administration of ZFA (OBZFA) failed to show the same phenomenon in either
      jejunum (P = 0.993) or ileum (P = 0.485). There was a significant difference in
      intestine apoptosis in either jejunum (P < 0.001) or in ileum (P < 0.001) between
      OBZLLY group and OBZFA group. Significantly increased intestine apoptosis
      occurred after common bile duct ligation. The administration of Z-LLY-FMK could
      effectively diminish the intestine apoptosis after common bile duct ligation,
      whereas the administration of ZFA-FMK failed to show the same effect.

PMID- 19093201
TI  - A pilot study about tolerability to double balloon endoscopy: comparison to
      esophagogastroduodenoscopy and colonoscopy.
AB  - BACKGROUND: Although the diagnostic and therapeutic values of double balloon
      endoscopy (DBE) have been investigated, the subjective tolerability to DBE has
      not been assessed. We aimed to evaluate patients' tolerability to DBE. METHODS:
      We prospectively enrolled patients who underwent DBE. For the comparison of
      tolerability to DBE with that to esophagogastroduodenoscopy (EGD) and
      colonoscopy, those who had not undergone EGD nor colonoscopy were excluded. A
      total of 52 patients were included. All procedures were performed under conscious
      sedation with midazolam with or without pethidine. Patients' tolerability to DBE,
      EGD, and colonoscopy was assessed through an interview with a questionnaire using
      a 10-point Likert scale. RESULTS: A total of 36 patients underwent both antegrade
      DBE and EGD under conscious sedation. The level of abdominal pain during
      procedures, the level of post-procedural abdominal discomfort, and the proportion
      of patients with persistent abdominal discomfort until the next morning were
      higher in antegrade DBE. However, when analyzed in 16 patients who had good
      quality of sedation, the differences in the level of abdominal pain during
      procedures and the persistent abdominal discomfort until the next morning
      disappeared. A total of 23 patients underwent both retrograde DBE and colonoscopy
      under conscious sedation. Tolerability parameters were not different between
      retrograde DBE and colonoscopy. Serious complications, including hemodynamic
      instability, did not occur during all procedures. CONCLUSION: Patients tolerated
      DBE well. DBE may be performed as comfortably as EGD and colonoscopy if the
      quality of sedation is good enough.

PMID- 19093202
TI  - Dietary Habits, demographical, and socio-economical risk factors of the newly
      diagnosed gastric cancers in the Eastern Anatolia Region of Turkey: an endemic
      upper gastrointestinal cancer region.
AB  - The Eastern Anatolia Region of Turkey is an endemic upper gastrointestinal
      (esophageal and gastric) cancer region, and the incidence of these cancers are
      still increasing in the region. We investigated demographic features, dietary
      habits, and some possible etiologic factors for this high prevalence. Special
      attention was given to the relationship between consumption of boiled yellow
      butter and the occurrence of gastric cancer. Age, sex, residential area, socio
      economical status, educational status, vegetable and fruit consumption, alcohol
      and tobacco use, tea consumption, boiled butter usage, cooking and storage
      methods of the patients with gastric cancer and controls were investigated in
      East Anatolian Regional Erzurum State Hospital. Helicobacter pylori infection for
      gastric cancer risk was not studied. Fruit, yellow-green vegetables, boiled
      butter, and breads baked by animal manure consumptions and no refrigeration are
      found to be statistically significant etiologic factors for gastric
      carcinogenesis. Dietary habits might be risk factors for gastric carcinogenesis
      among East Anatolian population. Some regional differences in food processing and
      preparation also seem to play a role in gastric carcinogenesis.

PMID- 19093203
TI  - Serum alpha-fetoprotein levels during and after interferon therapy and the
      development of hepatocellular carcinoma in patients with chronic hepatitis C.
AB  - The association between serum alpha-fetoprotein (AFP) levels during and after
      interferon (IFN) therapy and the development of hepatocellular carcinoma (HCC)
      was evaluated in patients with chronic hepatitis C (CHC). A total of 263 patients
      treated by IFN with or without ribavirin were enrolled in the study. Serum AFP
      levels during and after IFN therapy were investigated retrospectively, and
      statistical analysis was performed to identify the factors associated with HCC
      development. During IFN therapy, serum AFP levels significantly decreased,
      regardless of virologic response to treatment. Increased serum AFP levels (>or=10
      ng/ml) at the end of IFN therapy (EOT) was a close-to-significant variable
      affecting the development of HCC (P = 0.057), and a significantly higher
      cumulative incidence of HCC was seen in patients with increased serum AFP levels
      at EOT (P = 0.021). Serum AFP level at EOT is a possible predictor of HCC in CHC
      patients after IFN therapy.

PMID- 19093204
TI  - Acute cytomegalovirus infection is a risk factor in refractory and complicated
      inflammatory bowel disease.
AB  - The role of cytomegalovirus (CMV) infection in patients with inflammatory bowel
      disease (IBD) is controversial. Although CMV has been specifically associated
      with refractory disease, the strength and nature of this association have been a
      subject of debate. The aim of this study was to evaluate the prevalence and
      outcome of acute cytomegalovirus infection in patients with severe refractory and
      complicated inflammatory bowel disease. Seventy-two patients with active IBD
      (both ulcerative colitis [UC] and Crohn's diseases [CD]) were included in this
      study. Thorough history taking and physical examination of all patients was made
      with special emphasis on symptoms and signs of CMV disease. Colonoscopic
      assessment was made for the extent and activity of IBD and collection of
      specimen. Prevalence of CMV infection was estimated by serology; anti-CMV IgM and
      IgG antibodies, and pathologic studies of colonic biopsies used conventional
      haematoxylin and eosin (H & E) and immunohistochemistry (IHC) with monoclonal
      antibodies. Complete blood count and liver function tests were done for all
      patients. Among 72 patients with active inflammatory bowel disease, 23 (31.9%)
      were resistant to intravenous steroids. CMV was detected in eight (six with UC
      and two with CD) of the 23 (34.8%) steroid-resistant patients and in only one
      (3.2%) patient in the remaining 31 patients under steroid treatment and was not
      detected in 18 IBD patients not using steroids. Among nine CMV-positive IBD
      patients, six (66.6%) were female and six had fever; cervical lymphadenopathy was
      found in five patients and splenomegaly in two, compared to no patients in the
      CMV-negative group (P = 0.01 and 0.03, respectively). Leucopenia and
      thrombocytopenia were predominantly seen in the CMV-positive versus CMV-negative
      patients (2.1+/-0.3 vs. 5.9+/-3.4 and 98+/-34 vs. 165+/-101, respectively).
      Pancolitis was found in five of nine CMV-positive IBD patients whereas in only
      two patients out of 63 in the CMV-negative group (P = 0.005). Acute CMV infection
      in patients with IBD is not rare and is often underestimated. CMV infection in
      patients with refractory or complicated IBD should be ruled out before aggressive
      immunosuppressive therapy. High clinical index of suspicion for the association
      of CMV infection with IBD should be directed towards female IBD patients
      presenting with fever, lymphadenopathy, splenomegaly, leucopenia, and mild
      hepatitis. CMV IHC is significantly more sensitive than routine H & E stain and
      should be considered as part of the routine evaluation of IBD patients with
      severe exacerbation or steroid-refractory disease before proceeding with other
      medical or surgical therapy that may not be necessary once the CMV is treated.

PMID- 19093205
TI  - Comparing the acid-suppressive effects of three brands of generic lansoprazole
      with the original: pharmacokinetic bioequivalence tests do not necessarily
      guarantee pharmacodynamic equivalence.
AB  - Generic drugs contain the same active ingredient as an original drug and have
      their bioequivalence proved by pharmacokinetic tests. However, few studies have
      been reported on whether these bioequivalence studies infer pharmacodynamic
      equivalence. In this study, in eight healthy Helicobacter pylori-negative CYP2C19
      extensive metabolizers, we compared the acid-suppressive effects of repeated
      administration of 15 mg of three brands of generic lansoprazole, Taiproton,
      Tapizol, and Lansoral, with those of the original lansoprazole, Takepron. Median
      intragastric pH value for 24-h and % pH > 4 for daytime (08:00-20:00 h) and night
      time were significantly higher with any lansoprazole formulation, compared with
      the control (P < 0.05, Wilcoxon signed-rank test). However, during the daytime, %
      pH > 4 with Tapizol was significantly lower than the original (P < 0.05).
      Compared with the original, no significantly larger, but no small range of inter
      subject variations were observed in these two parameters for each of the three
      brands of generic lansoprazole (Bartlett test). Pharmacokinetic bioequivalence
      tests do not necessarily guarantee pharmacodynamic equivalence.

PMID- 19093206
TI  - Discriminative value of anorectal manometry in clinical practice.
AB  - Guidelines recommend anorectal manometry in patients with fecal incontinence and
      chronic constipation. However, limited evidence supports the utility of
      manometric testing. We retrospectively reviewed tracings obtained between
      November 2005 and May 2008. A total of 298 patients (86% women; average age 52
      years) were included. The main indications were incontinence (51%) and
      constipation (42%). Patients suffering from incontinence were older and had lower
      resting and squeeze pressure compared to continent patients. However, the
      discriminative power of manometric pressure data was poor, with low sensitivity
      and specificity. An abnormal straining pattern suggesting dyssynergic defecation
      was seen in 43% of constipated patients compared to 13% of patients with fecal
      incontinence. A concordance between manometric patterns and the balloon expulsion
      test was seen in 72%. The low sensitivity and specificity of manometric
      parameters does not support the routine use of anorectal manometry in patients
      with defecation disorders.

PMID- 19093207
TI  - Exposure to both radiation and chemotherapy increases the risk of Barrett's and
      multilayered epithelium.
AB  - The relationship between radiation and/or chemotherapy and the development of
      Barrett's and/or multilayered epithelium has not been investigated before. We
      ascertained a group of patients exposed to radiation and/or chemotherapy and an
      unexposed group to compare the prevalence rates of Barrett's epithelium and
      multilayered epithelium at the time of endoscopy in these two groups. Barrett's
      epithelium was found in ten of the 19 (53%) exposed patients, compared to eight
      of 38 (21%) unexposed subjects (P = 0.02). Six of 19 (32%) exposed patients had
      multilayered epithelium, compared to four of 38 (11%) unexposed subjects (P =
      0.06). Twelve of the 19 exposed patients (63%) had either Barrett's or
      multilayered epithelium, in contrast to ten of 38 (26%) unexposed subjects (P =
      0.01). Those with exposure to both chemotherapy and radiation had a significant
      increase in the risk for Barrett's and/or multilayered epithelium (P = 0.003).
      This study suggests a relationship between exposure to a combination of radiation
      and chemotherapy and the development of Barrett's and/or multilayered epithelium.

PMID- 19093208
TI  - Gastric pentadecapeptide BPC 157 and short bowel syndrome in rats.
AB  - The gastric pentadecapeptide BPC 157, which was shown to be safe as an antiulcer
      peptide in trials for inflammatory bowel disease (PL14736, Pliva), successfully
      healed intestinal anastomosis and fistula in rat. Therefore, we studied for 4
      weeks rats with escalating short bowel syndrome and progressive weight loss after
      small bowel resection from fourth ileal artery cranially of ileocecal valve to 5
      cm beneath pylorus. BPC 157 (10 microg/kg or 10 ng/kg) was given perorally, in
      drinking water (12 ml/rat/day) or intraperitoneally (once daily, first
      application 30 min following surgery, last 24 h before sacrifice).
      Postoperatively, features of increasingly exhausted presentation were: weight
      loss appearing immediately regardless of villus height, twofold increase in crypt
      depth and fourfold increase in muscle thickness within the first week, jejunal
      and ileal overdilation, and disturbed jejunum/ileum relation. In contrast,
      constant weight gain above preoperative values was observed immediately with BPC
      157 therapy, both perorally and parenterally, and villus height, crypt depth, and
      muscle thickness [inner (circular) muscular layer] also increased, at 7, 14, 21,
      and 28 days. Moreover, rats treated with pentadecapeptide BPC 157 showed not
      different jejunal and ileal diameters, constant jejunum-to-ileum ratio, and
      increased anastomosis breaking strength. In conclusion, pentadecapeptide BPC 157
      could be helpful to cure short bowel syndrome.

PMID- 19093210
TI  - Migrant drug users: predictors of HIV-related sexual and injection risk
      behaviors.
AB  - BACKGROUND: Puerto Rican drug users recruited in NY who previously used drugs in
      Puerto Rico (PR) have been found to have higher HIV injection and sex-related
      risk behaviors than those who had not used in PR. This study examined predictors
      of risk among migrant Puerto Rican drug users. (For the purpose of this paper,
      the term "migrant" was used to designate Puerto Rican drug users who had used
      drugs in Puerto Rico and were recruited in New York or New Jersey). METHODS: A
      total of 290 drug users who had previously used drugs in PR were recruited in NY
      and New Jersey and interviewed regarding drug use history and HIV risk behaviors.
      RESULTS: Participants engaged in high risk behaviors, e.g., 39% shared injection
      paraphernalia and 62% reported unprotected sex. Multivariate analyses found that
      predictors of injection-related risk included being born in PR and purchasing
      drugs jointly with other drug users; predictors of sex-related risk included
      younger age and homelessness. DISCUSSION: Addressing risk reduction among those
      drug users who were born in Puerto Rico and are younger or homeless was
      indicated, and efforts to reach those at highest risk through NEPs was
      recommended.

PMID- 19093211
TI  - Real time, non-invasive assessment of leaflet deformation in heart valve tissue
      engineering.
AB  - In heart valve tissue engineering, most bioreactors try to mimic physiological
      flow and operate with a preset transvalvular pressure applied to the tissue. The
      induced deformations are unknown and can vary during culturing as a consequence
      of changing mechanical properties of the engineered construct. Real-time
      measurement and control of local tissue strains are desired to systematically
      study the effects of mechanical loading on tissue development and, consequently,
      to design an optimal conditioning protocol. In this study, a method is presented
      to assess local tissue strains in heart valve leaflets during culturing. We
      hypothesize that local tissue strains can be determined from volumetric
      deformation. Volumetric deformation is defined as the amount of fluid displaced
      by the deformed heart valve leaflets in a stented configuration, and is measured,
      non-invasively, using a flow sensor. A numerical model is employed to relate
      volumetric deformation to local tissue strains in various regions of the leaflets
      (e.g. belly and commissures). The flow-based deformation measurement method was
      validated and its functionality was demonstrated in a tissue engineering
      experiment. Tri-leaflet, stented heart valves were cultured in vitro and during
      mechanical conditioning, realistic values for volumetric and local deformation
      were obtained.

PMID- 19093209
TI  - Steatocholecystitis and fatty gallbladder disease.
AB  - Obesity has become an epidemic worldwide. It is accompanied by a multitude of
      medical complications including metabolic syndrome. Obesity may lead to fatty
      infiltration of multiple internal organs including liver, heart, kidney, and
      pancreas, causing organ dysfunctions. Fatty infiltration leads to chronic
      inflammation and tissue damage. Fatty infiltration in the liver results in
      nonalcoholic fatty liver disease, which is increasingly common nowadays. Recent
      studies in animals and humans indicate that obesity also is associated with fatty
      infiltration of gallbladder, resulting in cholecystosteatosis. The increased
      gallbladder lipids include free fatty acids, phospholipids, and triglycerides.
      Enhanced inflammation with an increased amount of fat in the gallbladder results
      in an abnormal wall structure and decreased contractility. In support of this
      notion, a recent experiment on the effect of Ezetimibe, which is a novel drug
      that inhibits intestinal fat absorption, on fatty gallbladder disease reveals
      that Ezetimibe can ameliorate cholecystosteatosis and restore in vivo gallbladder
      contractility. The proportion of cholecystectomies performed for chronic
      acalculous cholecystitis has increased significantly over the past two decades.
      An increase in gallbladder fat, which leads to poor gallbladder emptying and
      biliary symptoms, may partly explain this phenomenon. Although dietary
      carbohydrates have been demonstrated to be associated with fatty gallbladder
      disease, other potential modifiable environmental factors are not clear. The
      pathogenesis and prognosis of fatty gallbladder disease, including
      steatocholecystitis, and the relations of fatty gallbladder disease to
      nonalcoholic fatty liver disease, including steatohepatitis, and other components
      of metabolic syndrome are largely unknown. More research is needed to answer
      these questions.

PMID- 19093213
TI  - Arsenic interactions with lipid particles containing iron.
AB  - While arsenic is toxic to all multicellular organisms, some organisms become
      tolerant by an unknown mechanism. We have recently uncovered an inducible
      tolerance mechanism in insects, which is based on a sequestration of toxins and
      pathogens by lipid particles. To examine whether arsenic interacts with lipid
      particles from mammals we compared binding of arsenic to lipid particles from
      insect and pig plasma after separation of lipid particles by low-density gradient
      centrifugation. Arsenic was found in both organisms in an area of the gradient,
      which corresponds to lipid-rich lipid particles. Since iron is known to affect
      arsenic toxicity in some organisms, we asked whether iron may be present in lipid
      particles. When low density cell (LDC) gradient fractions were analysed for the
      presence of iron we detected a peak in very low-density fractions similar to
      those that carried arsenic. This could indicate that arsenic interacts with lipid
      particles that contain iron and, if arsenic is removed from the plasma by lipid
      particles, that would also reduce iron-containing lipid particles at the time of
      arsenic emergence in the plasma. To test this assumption we measured the iron
      content in plasma at various time periods after the toxin ingestion. This time
      course revealed that iron is depleted in plasma fractions when arsenic shows a
      peak. Our data suggest that arsenic interacts with invertebrate and vertebrate
      lipid particles that are associated with proteins that may lead to detoxification
      by cell-free or cellular sequestration mechanisms.

PMID- 19093214
TI  - Vitamin and mineral use and risk of prostate cancer: the case-control
      surveillance study.
AB  - BACKGROUND: Many studies have evaluated the association between vitamin and
      mineral supplement use and the risk of prostate cancer, with inconclusive
      results. METHODS: The authors examined the relation of use of multivitamins as
      well as several single vitamin and mineral supplements to the risk of prostate
      cancer risk among 1,706 prostate cancer cases and 2,404 matched controls using
      data from the hospital-based case-control surveillance study conducted in the
      United States. Odds ratios (OR) and 95% confidence intervals (CI) for risk of
      prostate cancer were estimated using conditional logistic regression model.
      RESULTS: For use of multivitamins that did not contain zinc, the multivariable
      odds ratios of prostate cancer were 0.6 for 1-4 years, 0.8 for 5-9 years, and 1.2
      for 10 years or more, respectively (p for trend = 0.70). Men who used zinc for
      ten years or more, either in a multivitamin or as a supplement, had an
      approximately two-fold (OR = 1.9, 95% CI: 1.0, 3.6) increased risk of prostate
      cancer. Vitamin E, beta-carotene, folate, and selenium use were not significantly
      associated with increased risk of prostate cancer. CONCLUSION: The finding that
      long-term zinc intake from multivitamins or single supplements was associated
      with a doubling in risk of prostate cancer adds to the growing evidence for an
      unfavorable effect of zinc on prostate cancer carcinogenesis.

PMID- 19093212
TI  - Advanced technologies for genomic analysis in farm animals and its application
      for QTL mapping.
AB  - Rapid progress in farm animal breeding has been made in the last few decades.
      Advanced technologies for genomic analysis in molecular genetics have led to the
      identification of genes or markers associated with genes that affect economic
      traits. Molecular markers, large-insert libraries and RH panels have been used to
      build the genetic linkage maps, physical maps and comparative maps in different
      farm animals. Moreover, EST sequencing, genome sequencing and SNPs maps are
      helping us to understand how genomes function in various organisms and further
      areas will be studied by DNA microarray technologies and proteomics methods.
      Because most economically important traits in farm animals are controlled by
      multiple genes and the environment, the main goal of genome research in farm
      animals is to map and characterize genes determining QTL. There are two main
      strategies to identify trait loci, candidate gene association tests and genome
      scan approaches. In recent years, some new concepts, such as RNAi, miRNA and
      eQTL, have been introduced into farm animal research, especially for QTL mapping
      and finding QTN. Several genes that influence important traits have already been
      identified or are close to being identified, and some of them have been applied
      in farm animal breeding programs by marker-assisted selection.

PMID- 19093216
TI  - Evaluating the effectiveness of routine water quality monitoring in Miyun
      reservoir based on geostatistical analysis.
AB  - This study used geographic information system techniques and geostatistics
      methods to evaluate the effectiveness of routine water quality monitoring in the
      western segment of the Miyun reservoir in Beijing. Methodologies as well as the
      sampling design are evaluated. The single-layer evaluation and three integrated
      evaluation methods including principal component analysis (PCA), ordinary kriging
      (OK)_Mean, and Mean_Layers were used to validate the effectiveness of evaluation
      methods, and the effectiveness of each sampling design was validated by comparing
      their errors. Results indicated that, while a single-layer evaluation only shows
      the trophic state of water at a specific level, an integrated evaluation
      synthetically analyzes and evaluates the trophic state of the entire water body.
      Furthermore, results of the integrated analysis show that a PCA method is more
      accurate and can represent the trophic state of the entire water body. The
      OK_Mean and Mean_Layers methods are only able to represent the mean level for
      trophic state of the entire water body but cannot reflect local trophic state and
      distribution details. Although methods used in the routine monitoring of Miyun
      reservoir have some similarities to the OK_Mean and Mean_Layers methods, their
      range of errors and uncertainty are greater because of a lack of detailed spatial
      continuous information. The analysis on the number of sampling points shows that,
      within a certain range of error, minor changes of sampling points will have no
      obvious impact on the monitoring results. For the routine monitoring of western
      Miyun reservoir, using only three to five sampling points for monitoring is
      inadequate. According to our analysis, it is more appropriate to use at least ten
      sampling points for monitoring these areas.

PMID- 19093217
TI  - Impact of bottom trawling on sediment characteristics--a study along inshore
      waters off Veraval coast, India.
AB  - The present communication is a study on the impact of bottom trawling on the
      sediment characteristics along Veraval coast, which is the largest trawler port
      of India. Experimental bottom trawling was conducted from MFV Sagarkripa at five
      transects of water depths 15-20 m, 21-25 m, 26-30 m, 31-35 m and 36-40 m in
      commercial trawling grounds. Trawling was conducted for 12 months in a span of 15
      months (September 2005-November 2006) excluding the trawl ban period (June to
      August). The sediment texture was analysed by pipette analysis and organic matter
      by wet oxidation method. The variations in organic matter and sediment texture
      were prominent between the stations selected at different depths. The sedimentary
      organic matter exhibited variations with different water depths and seasons. The
      organic matter content decreased with depth. Experimental trawling considerably
      reduced the organic matter content at all depths. Continued and incessant
      trawling operation can cause even more drastic reductions, where organic matter
      (OM) content is already very small. The sand proportion showed depth-wise
      variation; but seasonal and trawling effect was not significant showing highest
      values at 36-40 m depth. The silt proportion did not exhibit significant depth
      wise variation. The seasonal variation of silt was significant whereas trawling
      effect imparted to silt was not evident. Trawling has no significant effect on
      clay concentration. But seasonal variation had great influence on the clay
      distribution and indicated significantly high depth-season interaction. The
      sediment of the study area was predominant in silt proportion. It was observed
      that the seasonal/natural variations were more prominent masking the trawling
      effect on silt.

PMID- 19093215
TI  - Galpha13 regulates MEF2-dependent gene transcription in endothelial cells: role
      in angiogenesis.
AB  - The alpha subunit of heterotrimeric G13 protein is required for the embryonic
      angiogenesis (Offermanns et al., Science 275:533-536, 1997). However, the
      molecular mechanism of Galpha13-dependent angiogenesis is not understood. Here,
      we show that myocyte-specific enhancer factor-2 (MEF2) mediates Galpha13
      dependent angiogenesis. Our data showed that constitutively activated
      Galpha13Q226L stimulated MEF2-dependent gene transcription. In addition,
      downregulation of endogenous Galpha13 inhibited thrombin-stimulated MEF2
      dependent gene transcription in endothelial cells. Both Ca(2+)/calmodulin
      dependent kinase IV (CaMKIV) and histone deacetylase 5 (HDAC5) were involved in
      Galpha13-mediated MEF2-dependent gene transcription. Galpha13Q226L also increased
      Ca(2+)/calmodulin-independent CaMKIV activity, while dominant negative mutant of
      CaMKIV inhibited MEF2-dependent gene transcription induced by Galpha13Q226L.
      Furthermore, Galpha13Q226L was able to derepress HDAC5-mediated repression of
      gene transcription and induce the translocation of HDAC5 from nucleus to
      cytoplasm. Finally, downregulation of endogenous Galpha13 and MEF2 proteins in
      endothelial cells reduced cell proliferation and capillary tube formation.
      Decrease of endothelial cell proliferation that was caused by the Galpha13
      downregulation was partially restored by the constitutively active MEF2-VP16. Our
      studies suggest that MEF2 proteins are an important component in Galpha13
      mediated angiogenesis.

PMID- 19093218
TI  - Emission inventory of evaporative emissions of VOCs in four metro cities in
      India.
AB  - High concentrations of volatile organic compounds (VOCs) in ambient air of urban
      areas stress the need for the control of VOC emissions due to the toxic and
      carcinogenic nature of many VOCs commonly encountered in urban air. Emission
      inventories are an essential tool in the management of local air quality, which
      provide a listing of sources of air pollutant emissions within a specific area
      over a specified period of time. This study intended to provide a level IV
      emission inventory as par the United States Environmental Protection Agency
      (USEPA) definition for evaporative VOC emissions in the metro cities of India
      namely Delhi, Mumbai, Chennai, and Kolkata. The vehicular evaporative emissions
      are found to be the largest contributor to the total evaporative emissions of
      hydrocarbons followed by evaporative losses related to petrol loading and
      unloading activities. Besides vehicle-related activities, other major sources
      contributing to evaporative emissions of hydrocarbons are surface coating, dry
      cleaning, graphical art applications, printing (newspaper and computer), and the
      use of consumer products. Various specific preventive measures are also
      recommended for reducing the emissions.

PMID- 19093219
TI  - Texas National Coastal Assessment (2000-2004): challenges, solutions, lessons
      learned and future directions.
AB  - The Texas National Coastal Assessment (NCA) program began with the immediate
      challenge of integrating the NCA effort with Texas Parks and Wildlife
      Department's (TPWD) Coastal Fisheries Division and its existing probabilistic
      Fishery Independent Monitoring Program. Close coordination and detailed planning
      along with a novel two boat sampling operation helped to make this alliance work.
      Partnerships with National Estuary Programs and the Texas Commission on
      Environmental Quality (TCEQ) greatly improved coverage of the Texas coast over
      the initial fifty station design. Airboats, biobags, and polyvinyl chloride (PVC)
      corers were instrumental in overcoming numerous technical challenges. NCA data
      provide a more complete assessment of water and sediment quality than the
      traditional 305(b) report, with better spatial coverage and a measure of
      validity. There were differing patterns of PCBs, PAHs, DDTs and chlorinated
      pesticides, and metals such as mercury (Hg), arsenic (As), lead (Pb) and zinc
      (Zn) along the Texas coast. A confederation of Texas state agencies is
      considering ways to take advantage of probabilistic sampling designs to monitor
      the Texas coast. The TCEQ and TPWD are working on a joint project to redesign
      sediment and water quality monitoring that may serve as a springboard to a
      continuous monitoring program and opportunities for further improvement of
      ecosystem health assessment of the Texas coast.

PMID- 19093220
TI  - The relationship between trace elements in fish otoliths of wild carp and
      hydrochemical conditions.
AB  - The trace element composition of the fish otolith is an indicator of
      biomineralization. In contrast to other skeletal tissue, the otolith retains its
      entire original structure and does not absorb any elements after the fish dies.
      Because otoliths in carp degrade very slowly in the dead body, the information it
      provides on the environment is retained, even in fossil form. Here, we report our
      analysis of the trace elements in otoliths of carp and of the water in Donghu
      Lake and Longhupao Lake, Heilongjiang province, China, where the fish lived. The
      results revealed that the trace elements found in the carp otoliths were clearly
      correlated with those found in these water bodies. There were high concentrations
      of Au, Ba, K, Sr and Zn in both the water and otoliths; in contrast there were
      high levels of As, Na and Se in water, but low concentrations in otoliths. These
      results indicate that an analysis of the otoliths of carps provides an accurate
      procedure for studying the surrounding hydrochemistry conditions. The interaction
      of the elements during deposition was also studied. The correlation coefficients
      of 13 trace elements identified in the otoliths in both lakes were calculated.

PMID- 19093221
TI  - Physiological responses to starvation in the European eel (Anguilla anguilla):
      effects on haematological, biochemical, non-specific immune parameters and skin
      structures.
AB  - The physiological effects of short-term starvation on some haematological,
      biochemical and non-specific immune response parameters together with the
      histological structure of the skin, were investigated in the European eel,
      Anguilla anguilla. Blood haemoglobin and haematocrit, serum glucose and cortisol,
      hemolysins, haemagglutinins, and lysozyme in the plasma, kidney and epidermal
      extract, were measured in fish after 31, 42 and 58 days of starvation, and
      compared to those of fed fish. Starvation did not affect haemoglobin and
      haematocrit values, while an increase in glucose and cortisol levels was found in
      starved eels by day 42. Haemolytic and haemagglutinating activities decreased in
      starved eels. On the other hand, starvation caused an increase in the lysozyme
      content in the epidermal extracts, while no significant variations were observed
      in kidney and plasma. On the whole, no major changes in metabolic, haematological
      and non-specific immune parameters were observed when short-term (less than 2
      months) starvation was applied to the European eel, suggesting an adaptive
      response to starvation, rather than a typical alarm-stress response, allowing
      this species to withstand food deprivation.

PMID- 19093222
TI  - Spectral sensitivity of juvenile chub mackerel (Scomber japonicus) in visible and
      ultraviolet light.
AB  - Although chub mackerel (Scomber japonicus) is widely distributed all over the
      world, the relevance of its visual sensitivity to its ecology is not yet fully
      understood. We investigated spectral sensitivity in juvenile chub mackerel in the
      range of ultraviolet (UV) to visible light (369-652 nm) by electroretinogram
      (ERG) using light-emitting diodes (LEDs). Sensitivity peaked at a wavelength of
      approximately 482 nm in dark-adapted fish and 525 nm in light-adapted fish. A
      secondary sensitivity peak in the UV range at approximately 382 nm was found in
      both dark- and light-adapted fish. The UV sensitivity of chub mackerel may be
      attributable to UV transmissibility of the optical media and to the presence of a
      beta-band of visible light-sensitive visual pigments, and not to an alpha-band of
      UV visual pigments. This UV sensitivity may be useful for feeding or
      communication with other fishes.

PMID- 19093224
TI  - Transgenic Technology meeting 2008 in Toronto, Canada: a meeting report.
AB  - In a history that goes back to 1999, the Transgenic Technology meetings started
      out in Sweden and over the years began to attract a growing community of
      technicians and researchers mainly from Europe. As the meetings started to
      attract an expanding worldwide audience, the community decided to found the
      International Society for Transgenic Technologies at the Barcelona meeting in
      2005. The 2007 convention was held at Brisbane, Australia, and in 2008, the 8th
      Transgenic Technology meeting was held for the second time on behalf of ISTT and
      for the second time outside of Europe in Toronto, Canada. Due to its excellent
      program with over 400 participants the meeting was able to attract the highest
      number of delegates of all past TT meetings. With extended times for plenary
      discussions about technical and organizational aspects, as well as top level
      scientific presentations, both technicians and scientists enjoyed this as an
      extremely fruitful meeting from which they could take home solutions for daily
      routines as well as new insights and ideas for coming projects.

PMID- 19093223
TI  - Cloning, characterization and expression analysis of a CXCR1-like gene from
      mandarin fish Siniperca chuatsi.
AB  - In this study we cloned and characterized a CXCR1-like gene (mfCXCR1) from
      mandarin fish (Siniperca chuatsi). The full-length cDNA of mfCXCR1 is 2,173 bp
      and contains a 1,056 bp open reading frame (ORF) that encodes a protein of 351
      amino acids. The 5' and 3' untranslated regions (UTR) are 57 and 1,080 bp in
      length, respectively. The coding region of the mfCXCR1 gene consists of a single
      exon with a 734 bp intron that is two nucleotides upstream of the ATG start codon
      in the 5' UTR. The mfCXCR1 protein shares a relatively high identity with the
      CXCR1 and CXCR2 proteins of other fishes (approximately 50-65%). Furthermore,
      phylogenetic analysis indicates a close relatedness of mfCXCR1 to CXCR1 of other
      fishes. Many binding sites for stress-inducible transcription factors were
      present in the promoter region of the mfCXCR1 gene, indicating that it might be
      activated by certain stressors. The level of mfCXCR1 mRNA, when normalized to
      that in liver (1-fold), was highest in spleen (approximately 192.9-fold), with
      intermediate levels in kidney (approximately 163.2-fold), blood (approximately
      131.2-fold) and head kidney (approximately 109.4-fold), and relatively low levels
      in intestine (approximately 34.4-fold) and gill (approximately 16.4-fold) (P <
      0.05). Expression of mfCXCR1 during the clinical stage of infectious spleen and
      kidney necrosis virus (ISKNV) infection showed that its expression was regulated
      over the course of infection. On day 4 after ISKNV challenge, mfCXCR1 expression
      was down-regulated in blood (approximately 0.91-fold), spleen (approximately 0.26
      fold), head kidney (approximately 0.18-fold) and kidney (approximately 0.82
      fold).

PMID- 19093225
TI  - Caution! Analyze transcripts from conditional knockout alleles.
AB  - A common strategy for conditional knockout alleles is to "flox" (flank with loxP
      sites) a 5' exon within the target gene. Typically, the floxed exon does not
      contain a unit number of codons so that the Cre-mediated recombination event
      yields a frameshift and a null allele. Documenting recombination within the
      genomic DNA is often regarded as sufficient proof of a frameshift, and the
      analysis of transcripts is neglected. We evaluated a previously reported
      conditional knockout allele for the beta-subunit of protein farnesyltransferase.
      The recombination event in that allele-the excision of exon 3-was predicted to
      yield a frameshift. However, following the excision of exon 3, exon 4 was skipped
      by the mRNA splicing machinery, and the predominant transcript from the mutant
      allele lacked exon 3 and exon 4 sequences. The "Deltaexon 3-4 transcript" does
      not contain a frameshift but rather is predicted to encode a protein with a short
      in-frame deletion. This represents a significant concern when studying an enzyme,
      since an enzyme with partial function could lead to erroneous conclusions. With
      thousands of new conditional knockout alleles under construction within mouse
      mutagenesis consortiums, the protein farnesyltransferase allele holds an
      important lesson-to characterize knockout alleles at both the DNA and RNA levels.

PMID- 19093226
TI  - Cloning, chromosomal localization, SNP detection and association analysis of the
      porcine IRS-1 gene.
AB  - Insulin receptor substrate-1(IRS-1) gene is one member of the Insulin receptor
      substrate (IRS) gene family, which plays an important role in mediating the
      growth of skeletal muscle and the molecular metabolism of type 2 diabetes. Here,
      we cloned a 3,573 bp fragment of the partial CDS sequence of porcine IRS-1 gene
      by in silicon cloning strategy and RT-PCR method. The porcine IRS-1 gene was
      assigned to SSC15q25 by using IMpRH. Sequencing of PCR products from Duroc and
      Tibetan pig breeds identified one SNP in exon 1 of porcine IRS-1 gene (C3257A
      polymorphisms). Association analysis of genotypes with the growth traits, anatomy
      traits, meat quality traits and physiological biochemical indexes traits showed
      that different genotypes at locus 3,257 of IRS-1 have significant differences in
      carcass straight length in pigs (P = 0.0102 ? 0.05).

PMID- 19093227
TI  - Water hyacinth as carbon source for the production of cellulase by Trichoderma
      reesei.
AB  - Water hyacinth (Eichhornia crassipes), an aquatic weed common to the
      subtropic/tropical regions, was utilized as an inexpensive lignocellulosic
      substrate for production of cellulase by Trichoderma reesei. The effects of
      process parameters like substrate pretreatment, substrate concentration, initial
      medium pH, mode of inoculation, and incubation temperature on cellulase
      production were investigated. Under optimal conditions, a maximal cellulase
      activity of 0.22 +/- 0.04 IU/ml (approximately 73.3 IU/g cellulose) was recorded
      at the end of 15-day incubation period. Specific activity of the enzyme was 6.25
      IU/mg protein. Hydrolysis of 1% substrate (water hyacinth) using crude enzyme
      dosage of 1.2 IU/g water hyacinth showed 28.7% saccharification in 1 h. The
      observations in present study indicate that saccharification of cellulose from
      water hyacinth was significantly higher by laboratory-produced cellulase than the
      commercial blend.

PMID- 19093228
TI  - Effect of nutrients on fermentation of pretreated wheat straw at very high dry
      matter content by Saccharomyces cerevisiae.
AB  - Wheat straw hydrolysate produced by enzymatic hydrolysis of hydrothermal
      pretreated wheat straw at a very high solids concentration of 30% dry matter
      (w/w) was used for testing the effect of nutrients on their ability to improve
      fermentation performance of Saccharomyces cerevisiae. The nutrients tested were
      MgSO4 and nitrogen sources; (NH4)2SO4, urea, yeast extract, peptone and corn
      steep liquor. The fermentation was tested in a separate hydrolysis and
      fermentation process using a low amount of inoculum (0.33 g kg(-1)) and a non
      adapted baker's yeast strain. A factorial screening design revealed that yeast
      extract, peptone, corn steep liquor and MgSO4 were the most significant factors
      in obtaining a high fermentation rate, high ethanol yield and low glycerol
      formation. The highest volumetric ethanol productivity was 1.16 g kg(-1) h(-1)
      and with an ethanol yield close to maximum theoretical. The use of urea or
      (NH4)2SO4 separately, together or in combination with MgSO4 or vitamins did not
      improve fermentation rate and resulted in increased glycerol formation compared
      to the use of yeast extract. Yeast extract was the single best component in
      improving fermentation performance and a concentration of 3.5 g kg(-1) resulted
      in high ethanol yield and a volumetric productivity of 0.6 g kg(-1) h(-1).

PMID- 19093229
TI  - Plasma homocysteine levels, the prevalence of methylenetetrahydrofolate reductase
      gene C677T polymorphism and macrovascular disorders in systemic sclerosis: risk
      factors for accelerated macrovascular damage?
AB  - The purpose of this study was to investigate plasma homocysteine (Hcy) levels in
      patients with systemic sclerosis (SSc) and to study the association between
      plasma Hcy, C677T polymorphism of 5,10-methylenetetrahydrofolate reductase
      (MTHFR), and the clinical manifestations in SSc. Associations of Hcy level, C677T
      MTHFR polymorphism, and macrovascular diseases were investigated in 152 patients
      with SSc and 58 controls. No significant differences in Hcy levels and MTHFR
      genotypes were found in SSc patients compared to controls or in SSc patients with
      limited cutaneous compared to diffuse disease. Significantly higher Hcy
      concentration was observed in patients with macroangiopathy/thromboembolic events
      compared to patients without such clinical manifestations (p < 0.05). There was
      significant correlation between age and macrovascular disorders, between Hcy
      level and the disease duration (r = 0.164; p < 0.05). Seventy-one percent of
      patients with macrovascular disorders had MTHFR polymorphism. In addition, 45% of
      patients with hyperhomocysteinemia had pulmonary hypertension. The presence of
      MTHFR C677T mutation influences the incidence of macrovascular abnormalities in
      SSc patients. Elevated Hcy levels may be associated with disease duration and the
      evolution of macrovascular disorders and pulmonary hypertension in SSc.

PMID- 19093230
TI  - Cancer stem cells: lessons from melanoma.
AB  - The model of cancer stem cells in tumor development states that tumors contain a
      subset of cells that both self renew and give rise to differentiated progeny.
      Like normal adult tissue stem cells, cancer stem cells are a minority of the
      whole tumor and are the only cells that are able to maintain tumor growth
      indefinitely. In the present review is critically discussed the actually
      existence of a cancer stem cell subpopulation in melanoma. The self-renewal
      signaling pathways as well as specific markers like as CD133, ABCB5 and ABCG2
      recently identified in putative melanoma cancer stem cells are also discussed.

PMID- 19093231
TI  - Serum levels of epidermal growth factor and HER-2 neu in non small-cell lung
      cancer: prognostic correlation.
AB  - Lung cancer is still a leading cause of cancer related mortality all over the
      world with the majority of cases are discovered at a late stage. Various panels
      of molecular prognostic markers are being studied to map the association of these
      markers with response and survival. The aim of this study is to study levels of
      epidermal growth factor receptor (EGFR), HER-2 neu in both serum and
      bronchoalveolar lavage (BAL) in patients with non small-cell lung cancer (NSCLC),
      correlate their levels with clinical, pathological characters as well as
      prognosis. A total of 30 patients with pathologically proven NSCLC were enrolled
      in this study in addition to ten normal controls subjects and ten cases with
      benign pulmonary diseases as broncheicatsis, chronic obstructive pulmonary
      disease. Results revealed significantly increased levels of EGFR and HER-2 neu in
      both serum and bronco-alveolar lavage compared with controls. The levels were
      significantly higher in those with stages III, IV compared with I, II, and in
      those with higher grades of the tumor. There was no statistically significant
      correlation with performance status or survival. In conclusion, serum measurement
      of these markers is a promising noninvasive technique which needs correlation
      with other methods of determination, measurement at different chronological
      points during disease evolution to explore its full potential. Standardization of
      techniques for determination of EGFR and HER-2 neu over-expression must become a
      priority in future studies that should also include larger number of patients,
      conducted in a prospective manner together with comparisons of various methods
      and correlation of protein expression with gene copy numbers.

PMID- 19093234
TI  - Abnormal bleeding associated with preeclampsia: a population study of 315,085
      pregnancies.
AB  - OBJECTIVE: To study the association of preeclampsia with abnormal bleeding in the
      first trimester and after delivery. DESIGN: Register-based population study.
      Setting. The Medical Birth Registry of Norway. Population. A total of 315,085
      women in Norway with singleton deliveries after 21 weeks of gestation (1999
      2004). METHODS: We compared frequencies of vaginal bleeding in the first
      trimester between women who subsequently developed preeclampsia and women without
      preeclampsia development, and made similar comparisons for postpartum bleeding.
      MAIN OUTCOME MEASURES: Proportion of women with bleeding. RESULTS: In the first
      trimester, vaginal bleeding occurred in 1.6% (215/13,166) of subsequent
      preeclampsia cases, compared to 2.0% (6,112/301,919) of normotensives (p<0.01).
      After delivery, excess postpartum bleeding (>1,500 mL) occurred in 3.0%
      (399/13,166) of preeclampsia cases and in 1.4% (4,223/301,919) of normotensives
      (p<0.01). Moderate bleeding postpartum (>500 mL) was also more common in
      preeclampsia cases (22.9% versus 13.9%, p<0.01). Similar patterns were present in
      first time mothers and in women with more than one birth, and the patterns did
      not vary according to type of delivery (cesarean section or not). CONCLUSIONS:
      These results suggest that factors associated with preeclampsia are inversely
      related to vaginal bleeding early in pregnancy, but positively associated with
      excess bleeding after delivery.

PMID- 19093235
TI  - Myomectomy during cesarean section.
AB  - OBJECTIVE: To evaluate the safety and effectiveness of myomectomy during cesarean
      section (CS). Design. Retrospective case-control study. SETTING: Tertiary
      referral university hospital. POPULATION AND METHODS: A study group of 1,242
      pregnant women with fibromyomas who underwent myomectomy during CS and three
      control groups of 200 matched pregnant women without fibromyomas who underwent CS
      deliveries (Group A), 145 patients with fibromyomas who underwent CS deliveries
      without removal of fibromyomas (Group B) and 51 patients with fibromyomas who had
      a hysterectomy during CS (Group C). MAIN OUTCOME MEASURES: The difference between
      pre- and postoperative hemoglobin levels, the incidence of hemorrhage, blood
      transfusion, postoperative fever, duration of operation and length of hospital
      stay. RESULTS: No difference was found in the median parity or mean gestational
      age, but maternal age was higher and the gestational age lower in Group C than
      the study group. The median number and diameter of fibromyomas in Group B were
      lower than in the study group. Compared to the study group, Group B women had
      more single fibromyomas, while those in Group C had more multiple fibromyomas.
      Group B had more uterine cornual fibromyomas than the study group. There were no
      differences in the mean hemoglobin change, the incidence of postoperative fever
      and the length of hospital stay among groups. CONCLUSION: Myomectomy during CS
      was a safe and an effective procedure.

PMID- 19093236
TI  - The efficacy of conservative management after conization in patients with stage
      IA1 microinvasive cervical carcinoma.
AB  - OBJECTIVE: To investigate the efficacy of conization followed by conservative
      management for treating stage IA1 microinvasive carcinoma of the uterine cervix.
      DESIGN/SETTING: Retrospective study. POPULATION: Seventy-five patients treated
      for stage IA1 microinvasive carcinoma of the cervix. Patients underwent
      conization followed by hysterectomy (Group 1, 53 patients), or were followed by
      conservative management (Group 2, 22 patients). METHODS: Medical and
      histopathological record review. RESULTS: For Group 1, pathology results showed
      that 30 had no residual tumor, one had cervical intraepithelial neoplasia (CIN)
      I, 11 had CIN III/cervical carcinoma in situ (CIS), nine had microinvasive
      carcinomas, and one had an invasive carcinoma (outcome for one patient not
      recorded). For Group 2, secondary procedures involved only cervical smears for 12
      (48%) patients, of whom nine had normal cytology, one had low-grade squamous
      intraepithelial lesion and two had high-grade squamous intraepithelial lesions.
      For 13 (52%) patients in Group 2, secondary procedures involved repeat conization
      on whom six had no residual tumor, one had CIN II, four CIN III/CIS, and two
      microinvasive carcinoma and a negative resection margin. Therefore, conization
      followed by conservative management was an effective treatment for 90.9% (20/22)
      of Group 2. In neither group was recurrence recorded. There was no relation
      between lymphovascular invasion and follow-up cytology or pathology results, or
      between resection margin status and follow-up examination results. CONCLUSION:
      Conization alone with careful follow-up appears to be an effective and safe
      treatment for patients with stage IA1 microinvasive carcinoma of the uterine
      cervix, regardless of resection margins status or lymphovascular invasion.

PMID- 19093237
TI  - Illuminance, sexual maturation, and early egg production in female broiler
      breeders.
AB  - 1. Broiler breeders were reared at an initial illuminance of 13, 21 or 44 lux and
      transferred at 20 weeks and a mean body weight of 2.06 kg to floor pens at 25, 55
      or 71 lux, or to individual cages at various intensities between 3 and 138 lux.
      2. Rate of sexual maturation was not significantly affected by the light
      intensity experienced during the rearing period, but was progressively
      accelerated by the provision of a brighter illuminance after 20 weeks, up to a
      ceiling of about 14 lux. There was no interaction between the pre- and post-20
      week illuminance. 3. Cumulative egg numbers to 39 weeks were unaffected by
      illuminance in the rearing period, positively correlated with illuminance post 20
      weeks up to an asymptote at about 8 lux, and highly correlated with age at sexual
      maturity. Peak rate of lay was both delayed and depressed at 3 lux. 4. It is
      concluded that the minimum light intensity required at bird-head height to
      achieve satisfactory photostimulation and an optimal peak rate of lay in broiler
      breeders is 10 lux, but that a higher illuminance would be prudent for broiler
      breeders kept in floor pen facilities to maximise nest-box usage.

PMID- 19093238
TI  - Feeding layers of different genotypes in organic feed environments.
AB  - 1. Two experiments were carried out to evaluate the suitability of an
      experimental laying hen genotype (SH) in organic egg production. SH had been
      selected over 25 generations on a low protein diet (130 g/kg) based on home grown
      feedstuffs. SH hens were compared with LSL (Experiment 1) and Hyline (Experiment
      2) hens. The birds were kept in 12 aviary pens with access to outdoor runs. 2.
      Four diets, which were different in each experiment, were used. A control diet
      was compared with diets based on feedstuffs supposed to be able to be grown and
      produced according to organic standards. The diets differed in the content of
      sulphur amino acids. 3. There were no significant differences in mortality caused
      by diets or genotypes but an incidence of cannibalism occurred in one Hyline
      group fed on the diet with the lowest methionine content. 4. Severe feather
      pecking of LSL birds occurred and was worst on the low protein diet. In
      Experiment 2, signs of feather pecking of birds on the low protein diet occurred
      at the end of the experiment, but there was no difference between the genotypes.
      There was no significant difference in number of eggs produced between diets. Egg
      weight was influenced by diets in both experiments and by genotype in Experiment
      2. Number of misplaced eggs was higher in SH hens in both experiments. There were
      few significant diet x genotype interactions. 5. The use of the outdoor area was
      influenced by diets and genotype in both experiments. 6. In conclusion, diets low
      in methionine content influenced predominantly plumage condition and egg weight,
      although production of eggs by number was unaffected. The SH hen adapted well to
      organic conditions, as did the Hyline genotype.

PMID- 19093239
TI  - Broiler embryo bone development is influenced by incubator temperature, oxygen
      concentration and eggshell conductance at the plateau stage in oxygen
      consumption.
AB  - 1. Four experiments were conducted to evaluate the effects of temperature (TEM)
      and oxygen (O(2)) concentrations during the last 4 d of incubation on bone
      development. Fertile eggs from two strains were obtained that either exhibited
      Low or High eggshell conductance (G). 2. Four experimental cabinets provided
      either four TEM (36, 37, 38 or 39 degrees C) or four O(2) concentrations (17, 19,
      21 or 23% O(2)). Data were analysed as a 2 x 2 factorial design. In the fourth
      experiment, two temperatures (36 and 39 degrees C), two O(2) concentrations (17
      and 23%) and the same Low and High G strains were evaluated in a 2 x 2 x 2
      factorial design. 3. Body weights (BW) and residual yolks were obtained, both
      legs were dissected. Femur, tibia and shank weights, length and thickness were
      recorded. Relative asymmetry (RA) of each leg section was calculated. 4. The
      results indicated that elevated TEM during incubation increased RA between the
      two legs, mainly in the Low G strain. Chickens at the lowest O(2) concentrations
      had lighter and shorter tibias, lighter shanks, and increased RA of femur length
      compared to chickens in the 23% O(2). In the fourth experiment no interactions
      were observed between O(2) and TEM. High TEM depressed BW of Low G broilers, but
      no significant effect of treatments was observed on BW of High G broilers.
      Nevertheless, the high TEM or low O(2) independently caused reduced femur and
      tibia weights and length, shank length and thickness, and both low O(2) and high
      TEM together increased RA in shank weight. 5. These results suggest that late
      incubation conditions affect long bone development in broilers.

PMID- 19093240
TI  - Changes in eggshell conductance, water loss and hatchability of layer hens with
      flock age and moulting.
AB  - 1. Changes in water loss, eggshell conductance and hatchability with flock age
      were monitored in layer hens in a commercial hatchery. 2. Optimal water loss for
      maximal hatchability of layer eggs was found to be 12 to 13% of initial egg mass
      at d 18 of incubation. 3. Mass specific water vapour conductance (GH(2)Osp)
      increased linearly with flock age from 0.31 mg/(d.g.Torr) at the beginning of the
      first breeding season to 0.40 mg/(d.g.Torr) at its end after 77 weeks (=4.21 and
      5.44 mg/(d.100 g.kPa), respectively). 4. After forced moulting GH(2)Osp increased
      from 0.35 to 0.41 mg/(d.g.Torr) (=4.76 and 5.58 mg/(d.100 g.kPa), respectively).
      5. The coefficients of variation of GH(2)Osp increased with flock age from 14% at
      the beginning of the breeding season to 31% at the end of the second breeding
      season. 6. In order to preserve normal incubation water loss for maximising
      hatchability, the humidity setting of an incubator should increase gradually,
      with flock age, from 53% RH to 66% RH in the first laying season and from 61% RH
      to 67% RH after forced moulting. 7. A 3.5-fold increase (from 2 to 7%) in the
      difference between mean and median GH(2)Osp of egg batches with flock age was
      found, indicating increasing frequency of microscopic cracks in eggshells with
      flock age. This has to be taken into account when setting the humidity regime in
      the incubator.

PMID- 19093241
TI  - Prevalence and factors associated with it, of birds dead on arrival at the
      slaughterhouse and other rejection conditions in broiler chickens.
AB  - 1. Standardised data on husbandry were recorded for a flock of birds in one house
      on each of 150 broiler farms in the UK during the 4 d prior to slaughter. 2. For
      each flock, the incidence of birds found dead on arrival (DoAs) and the Meat
      Hygiene Service carcase rejection records were recorded at the slaughterhouse. 3.
      The mean percentage of birds in each flock found DoA was 0.12% (range 0-0.64%)
      and the mean percentage of Total Carcase Rejects (TCRs) for each flock was 1.23%
      (range 0.07-5.51%). 4. A general linear model was developed to examine factors
      associated with flock percentage DoAs. Assuming a linear relationship, all other
      factors remaining the same, a one percentage point (PP) increase in
      small/emaciated birds will result in a 0.155 PP increase in DoAs and a 1 PP
      increase in wheat in diet 4 will result in a 0.003 PP decrease. An increase by
      one in the total number of vaccines administered will cause a 0.029 PP decrease
      in DoAs, a 1 g increase in live weight at slaughter will be associated with a
      0.000043 PP increase and a 1 PP increase in mortality on farm would be associated
      with a 0.000044 PP increase. A 1 PP increase in Ross birds decreases DoAs by
      0.0004 PPS: there is also a seasonal effect. 5. The model developed for flock
      percentage TCRs found that a 1 PP increase in wheat in diet 3 will result in a
      0.052 PP decrease in TCRs and a 1 PP increase in Ross birds will cause a 0.009 PP
      decrease. A 1 PP increase in birds culled on farm will be associated with a 0.03
      PP increase in TCRs and the diagnosis of disease during the flock cycle increases
      TCRs by 0.397 PPs. A one day increase in age at slaughter will result in a 0.046
      PP increase in TCRs.

PMID- 19093242
TI  - Effects of dietary vitamin E and C supplementation on heart failure in fast
      growing commercial broiler chickens.
AB  - 1. It has recently been shown that oxidative stress is involved in the
      pathogenesis of congestive heart failure (CHF) in broiler chickens. Vitamins E
      and C, common antioxidants, have been advocated for the prevention of heart
      failure in humans. The present study examines the effects of supplementation of
      these vitamins on incidence of CHF and prevention of oxidative stress in the
      myocardium. 2. Commercial male broilers were randomly allocated to three
      experimental groups and, respectively, offered commercial broiler diet (control),
      commercial diets fortified with vitamin E (960 IU/kg) or vitamin C (400 mg/kg).
      The broilers were monitored daily for overt signs of heart failure and clinical
      data including ECG and blood gas analysis were collected periodically. Lipid
      peroxidation was measured in cardiac tissues from apparently normal broilers and
      broilers developing CHF in each group using thiobarbituric acid reactive
      substances (TBARS) assay. 3. Overall, the incidence of CHF in broilers given
      diets fortified with vitamin E or vitamin C was not significantly different as
      compared to the control group. The incidence of overt signs of hypoxaemia was
      lower in the vitamin C group than in the control group. Lipid peroxidation was
      highest in broilers that developed CHF as compared to apparently normal broilers
      fed either vitamin E or C fortified diets. Neither vitamin E nor vitamin C was
      effective in preventing oxidative damage in broilers that developed CHF. 4. In
      conclusion, the present study confirmed that oxidative stress is involved in the
      pathogenesis of heart failure in broilers, but dietary supplementation of
      antioxidant vitamins did not prevent oxidative damage in broilers that developed
      CHF. Beneficial effects of vitamin C supplementation were evidenced by lower
      incidence of hypoxaemia, and the tendency to reduce the susceptibility of
      broilers to heart failure. However, vitamin E did not have any impact on clinical
      status or the incidence of CHF.

PMID- 19093243
TI  - Effects of reduced dietary calcium and phytase supplementation on calcium and
      phosphorus utilisation in broilers with modified mineral status.
AB  - 1. The impact of modified mineral status and dietary Ca:P ratio on Ca and P
      utilisation was measured in chicks with or without phytase supplementation. 2. In
      a preliminary study, 4 diets were given to chicks from 3 to 15 d of age: D1 (6.5
      g P/kg and Ca:P = 1.5) and D2, D3 and D4 (6.0, 5.4 and 5.0 g P/kg, respectively,
      and Ca:P = 1.2). Growth performance was similar across diets. Tibia ash was
      similar in chicks given D1 and D2, but was gradually depressed from D2 to D4 (
      22%). 3. In the depletion period, two groups of chicks, with similar performance,
      but with different mineral status were achieved by feeding them, from 5 to 15 d
      of age, diets with a similar Ca:P ratio of 1.2, but containing 6.3 or 5.2 g P/kg.
      4. During the subsequent 11 d of the repletion period, chicks from each of the
      two previous groups were given one of the 4 diets containing 5.7 g P/kg, but
      differing in their Ca (8.3 and 5.3 g Ca/kg) and microbial phytase (0 or 1000 FTU,
      Natuphos levels in a 2 x 2 x 2 factorial arrangement. 5. At the end of the
      repletion period, the initially depleted chicks could not be differentiated from
      the non-depleted chicks, indicating the capacity of chicks to compensate for
      their initial depleted mineral status. 6. Interaction between dietary Ca and
      phytase levels was not significant. Phytase improved growth performance and bone
      characteristics. Reduced dietary Ca enhanced feed intake and growth rate, but
      depressed bone dry matter and ash weight. 7. At the end, diets supplemented with
      phytase maximised bone ash weight when chicks were fed with a Ca:P ratio of 1.5
      but elicited the highest growth rate when chicks were fed with a Ca:P ratio of
      0.9.

PMID- 19093244
TI  - Relationship between digesta transit time and apparent metabolisable energy value
      of wheat in chickens.
AB  - 1. This study tested the hypotheses that: (a) apparent metabolisable energy (AME)
      values and whole tract transit time (WTTT) were related, and that (b) the
      relationship between AME and WTTT differed between male and female Ross broiler
      chickens. 2. Enzyme products with xylanase activity were added to a basal diet to
      provide 4 dietary treatments comprising control (no enzyme), Avizyme 1300 (1
      kg/tonne), Kemzyme W1 (1 kg/tonne), and Bio-Feed Wheat CT (200 g/tonne). The
      basal diet comprised (in g/kg), 800 wheat, 155 casein, 20 dicalcium phosphate, 11
      limestone, 7 D,L-methionine, 2 vitamin and mineral premix, 3 sodium chloride and
      2 choline chloride (60%). 3. AME values for diets were determined in a 7-d energy
      balance study commencing when chickens were 21 d of age. WTTT was the time
      elapsed (in min), from time of administration by oral gavage of 200 mg ferric
      oxide in a gelatine capsule, to time of first observation of the distinctive red
      colouration in droppings. 4. The mean AME value for the wheat was high (15.7
      MJ/kg dry matter) and ranged from 14.4 to 16.3 MJ/kg dry matter for individual
      birds. Mean WTTT was 206 min and ranged from 105 to 429 min. AME and WTTT were
      unaffected by enzyme addition to the diet, and the interaction between diet and
      gender was not significant. 5. There was a significant but weak positive
      relationship between AME and whole tract transit time, with AME increasing by 2.2
      kJ/min. This relationship was unaffected by gender of the chicken.

PMID- 19093245
TI  - The efficiency of energy retention of broiler chickens and turkeys fed on diets
      with different lysine concentrations.
AB  - 1. An experiment determined the effect of 6 different lysine concentrations (40,
      52, 58, 65, 90 and 130 g/kg CP) in two protein concentrations (210 and 260 g/kg)
      on the efficiency of energy utilisation of broiler chickens and turkeys. Ninety
      six male Ross 308 broiler chicks and 96 male BUT Big 6 turkey poults were fed at
      90% of ad libitum during a 12 d bioassay period. At the end of the bioassay,
      birds were slaughtered and carcase crude protein, fat and gross energy were
      measured and nutrient metabolisability determined. 2. Broiler chickens had lower
      AME and AME(N) than turkeys. AME was higher in the 260 g/kg than in the 210 g/kg
      protein diet; however, no difference was evident in AME(N) between any of the
      diets in both species. A significant species x lysine interaction indicated that
      the decrease in AME and AME(N) with increasing lysine was greater in turkeys than
      in broiler chickens. 3. Turkeys had lower weight gains and efficiencies of energy
      retention than broiler chickens. The effects of different lysine concentrations
      on growth and the efficiency of energy retention were significant and growth
      responses were quadratic but there were negative linear responses in the
      efficiency of energy retention in both species at both crude protein
      concentrations. The efficiency of energy retention was increased with decreasing
      lysine concentrations throughout the wide range of concentrations used in the
      experiment.

PMID- 19093246
TI  - Plasma glucose, mannose, and non-esterified fatty acid concentrations in layer
      type chickens.
AB  - 1. The oral administration of glucose or dietary glucose reduces fasting plasma
      mannose concentrations in mammals. On the other hand, there have been no reports
      on plasma mannose levels in birds. We have analysed chicken plasma mannose and
      glucose by an original high-performance liquid chromatography (HPLC) method,
      together with plasma non-esterified fatty acid (NEFA) concentrations in chickens.
      2. Plasma glucose concentrations of chickens did not differ among three different
      age groups (0, 18 and 150 d). However, the plasma mannose concentrations of
      chicks at the age of 0 d were higher than those of chickens at the ages of 18 and
      150 d. 3. At the age of 18 and 150 d, plasma glucose concentrations were elevated
      and plasma mannose and NEFA concentrations were decreased after regular feeding,
      compared to fasting levels.

PMID- 19093247
TI  - Effect of in ovo threonine supplementation on early growth, immunological
      responses and digestive enzyme activities in broiler chickens.
AB  - 1. The effects of injecting threonine in ovo on early growth, some immunological
      responses and the activity of digestive enzymes of broiler chicks were
      investigated. Fertile eggs were distributed into 6 groups, each of 60. These
      were: untreated control, sham control, 10, 20, 30 or 40 mg threonine. Threonine
      was dissolved in 0.5 ml sterile saline and inoculated into the yolk sac of the 14
      d-old embryo through the narrow end of the egg. 2. The ratio of chick to egg
      weight was 1.6% higher in the group given 30 mg threonine and at 28 d of age
      chicks receiving threonine were 29 to 79 g heavier than untreated controls. 3.
      Food conversion ratio until 7 d after hatching was improved in those chicks
      receiving 10, 20 or 40 mg threonine but there was no significant effect on the
      activities of amylase, pepsin or trypsin. 4. The humoral response to sheep red
      blood cells was significantly greater in those groups receiving 10, 20 or 30 mg
      threonine supplementation than in untreated controls. 5. The response to
      phytohaemagglutinin-P, a measure of the cell-mediated immune response, was not
      affected, however. 6. It is concluded that injections of 20 to 30 mg threonine
      into yolk sac can improve post-hatching growth and humoral responses of broiler
      chicks.

PMID- 19093248
TI  - Effect of the addition of ground rosemary on the quality and shelf-life of turkey
      meatballs during refrigerated storage.
AB  - 1. The aim of the present study was to determine the effect of the addition of
      ground rosemary on the quality and shelf-life of turkey meatballs. Heat-treated
      vacuum-packed turkey meatballs were stored at 3 +/- 1 degrees C. 2. The rate of
      oxidative and hydrolytic changes during refrigerated storage was slower in
      meatballs containing 1% of rosemary. The samples with rosemary were characterised
      by significantly lower values of pH and water activity than control samples. The
      addition of rosemary inhibited the growth of psychrotrophic, coliform and
      Clostridium sp. bacteria. 3. The sensory quality of meatballs decreased over
      storage, first in control samples and later also in those containing rosemary.
      Warmed-over flavour was detected after 12 d of storage in meatballs spiced with
      rosemary and after 3 d in control samples. A sour flavour was not perceptible in
      meatballs containing rosemary. The obtained results confirm the beneficial effect
      of rosemary added to poultry meat products.

PMID- 19093249
TI  - Seasonal variations in the crop contents of scavenging Helmeted Guinea Fowls
      (Numida meleagris, L.) in Parakou (Benin).
AB  - 1. An experiment was carried out with 120 helmeted guinea fowls during one year
      in Parakou (Benin). Feed intake, ingredient and chemical composition, along with
      the nutritional adequacy of scavenging diets were measured during the rainy
      season (November-February) and dry season (March-October) in order to propose
      supplementation strategies. Ingredients found in crops were identified and
      allocated into 6 main categories (supplemental feed, seeds, green forages, animal
      materials, mineral matter and unidentified materials). 2. Mean dry weights of
      crop contents were significantly higher in the rainy than in the dry season.
      Amounts and proportions of supplemental feed and seeds were not significantly
      different between seasons, whereas those of green forage, animal materials and
      mineral matter were higher in rainy season. Supplemental feed, especially maize
      and sorghum, was the largest component of the crop content in both seasons. The
      most represented grass seeds were Panicum maximum (rainy season) and Rottboellia
      cochinchinensis (dry season). 3. Dietary concentrations of organic matter, non
      nitrogen extract and metabolisable energy were higher in the dry season, while
      mineral concentrations were higher in the rainy season. There were no significant
      differences between the two seasons in dry matter, crude protein or crude fibre.
      4. Scavenging provided insufficient nutrients and energy to allow guinea fowls to
      be productive. Therefore, more nutritionally balanced supplementary feed would be
      required during both seasons.

PMID- 19093250
TI  - Influence of plasma lipid composition on activity of Factors V, VII and X in
      Single Comb White Leghorn and Fatty Liver Haemorrhagic Syndrome-susceptible
      laying hens.
AB  - 1. Plasma lipids were investigated to determine whether they influence the
      biological activities of specific coagulation proteins Factors V, VII and X. 2.
      Factor activities decreased when lipids were depleted from the plasma of Single
      Comb White Leghorn (SCWL) and Fatty Liver Haemorrhagic Syndrome-susceptible
      (FLHS) laying hens. 3. Addition of lipids removed from SCWL laying hens and FLHS
      susceptible laying hens into lipid-depleted plasma of both bird strains caused an
      increase and decrease, respectively, in Factors V and X activities. 4. Omega-3
      fatty acids were negatively correlated to Factors V, VII and X activities. When
      bird strain was considered, it was significant for Factor X in SCWL laying hens.
      Omega-6 fatty acids were positively correlated with Factors VII and X for FLHS
      susceptible laying hens. 5. The results suggest that the type of fatty acid in
      plasma phospholipids influences the activities of Factors V, VII and X and by
      altering lipid composition in the plasma, activities of coagulation factors may
      be affected.

PMID- 19093251
TI  - Analysis of sperm storage ability using duration of fertility in hens.
AB  - 1. The objective of this study was to determine hens' sperm storage potential. 2.
      Efficient duration (De, number of days between insemination and the first clear
      egg), maximum duration (Dm1, number of days from the day after insemination to
      the last fertile egg before two consecutive infertile eggs) and maximum duration
      (Dm2, number of days from the day after insemination to the last fertile egg) of
      fertility, fertile egg number, egg production, laying rate and fertility during
      the 24 d following the latter of two inseminations (with 1 x 10(8) spermatozoa)
      on two consecutive days were measured in a total of 150 dual-purpose hens at 30
      weeks of age. 3. De, Dm1 and Dm2 were 12.06, 14.44 and 16.17 d, respectively, and
      the three definitions of fertility duration (DF) differed greatly. 4. Significant
      correlation coefficients between De and Dm1, Dm1 and Dm2, and De and Dm2 were
      0.51, 0.57 and 0.23, respectively. 5. We suggest that De and fertile egg number
      should be used to assess the ability of storing spermatozoa in female fowl.

PMID- 19093252
TI  - Learning ability of 1-d-old partridges (Alectoris rufa) from eggs laid by hens
      fed with different n-3 fatty acid concentrations.
AB  - 1. The diets of commercial strains of laying partridge are usually lower in
      polyunsaturated fatty acids (PUFA) and n-3 fatty acids than the diets of wild
      partridges. The aim of this experiment was to examine the effects of three
      different PUFA and n-3 concentrations in partridge laying diets. 2. Offspring
      learning ability (passive avoidance test of 1-d-old chicks) was used to assess
      the effect of three different maternal diets (144 chicks were tested for each
      diet). A negative experience, allowing the bird to peck a bead bathed in a bitter
      liquid (methyl anthranilate-MA), was used for this purpose. The adults had been
      fed one of three different diets with n-3 contents of 0.48, 4.04 or 7.60 g/kg. 3.
      There was better memory retention in the offspring of adults fed the intermediate
      n-3 content compared to those fed the lower content. Discrimination ratio (DR) of
      the latency time toward the wrong (red) bead was less for the lower n-3 content
      (0.48) than for the middle n-3 PUFA content (0.43). DR of the number of pecks
      toward the wrong beads was greater for the lower n-3 content (0.51) than for the
      middle n-3 PUFA content (0.71). 4. The partridges fed the diet containing the
      lowest concentration of n-3 and PUFA were unable to express the expected
      behavioural score (neural embryo development index) given the genetic
      characteristics of the animals.

PMID- 19093253
TI  - Decoy receptor 3 overexpression and immunologic tolerance in hepatocellular
      carcinoma (HCC) development.
AB  - The recently identified decoy receptor 3 (DcR3) inhibits FasL-induced apoptosis
      by binding to FasL, and it is considered to play a key role in the immune escape
      system of neoplastic cells. In order to examine the involvement of DcR3 in the
      immunologic tolerance of hepatocellular carcinoma (HCC), we investigated the
      amplification and expression of DcR3, FasL, and Fas in an HCC mice model using RT
      PCR, western blotting, and ELISA, and analyzed the space-time relationship with
      various cytokines including the forkhead transcription factor forkhead/winged
      helix transcription factor gene (Foxp3), CTLA-4, TGF-beta, IL-10, TNF-alpha, and
      IFN-gamma. The RT-PCR results revealed that Fas expression preceded that of DcR3
      during the early phases of tumorigenesis. Thereafter, the expression of DcR3 was
      up-regulated; however, the expression of Fas was down-regulated and eventually
      ceased. DcR3 and FasL were expressed and amplified simultaneously in muscle
      tumor. CTLA-4 expression was earlier than Foxp3, and both CTLA-4 and Foxp3
      amplification and expression were consistent with that of DcR3. The results
      suggest that the elevated levels of DcR3, Foxp3, and CTLA-4 in tissue were
      positively correlated with tumor growth. The partial tumor immunoregulation
      inclined to negative modulation, and DcR3 may play an important role in inducing
      immunologic tolerance.

PMID- 19093254
TI  - Gorlin syndrome with ameloblastoma: a case report and review of literature.
AB  - A 32-year-old female patient with a history of surgical treatment of cutaneous
      basal cell carcinomas and recurrent keratocystic odontogenic tumours presented
      with a painless swelling in the vestibular area of the maxillary premolar region.
      The lesion was excised, and pathological examination established the diagnosis of
      ameloblastoma. A review of literature about Gorlin syndrome with ameloblastoma is
      presented.

PMID- 19093255
TI  - Expression of CD147 mediates tumor cells invasion and multidrug resistance in
      hepatocellular carcinoma.
AB  - Multidrug resistant (MDR) tumor cells over-expressing P-glycoprotein exhibit
      variation in invasive behavior. To investigate the mechanisms, we analyzed the
      expression of CD147. The results showed that CD147 expression was increased in
      HepG2/Adr cells, as compared to HepG2 cells. The MDR cells produced more MMP11
      and MDR1, which promoted HepG2/Adr cells invasion and increased resistance to
      chemotherapeutic drugs. On the other hand, CD147 silencing in HepG2/Adr cells by
      RNAi led to the opposite effect. Treatment of tumor cells with U-0126, an
      inhibitor of MAPK/Erk, also down-regulated MMP11 and MDR1 expression. Thus, CD147
      may functionally mediate tumor cells invasion and MDR.

PMID- 19093256
TI  - Inhibition of laryngeal cancer cell invasion and growth with lentiviral-vector
      delivered short hairpin RNA targeting human MMP-9 gene.
AB  - The purpose of this study was to explore the inhibiting role of MMP-9 gene
      silence in the invasive ability and growth of laryngeal squamous cell carcinoma
      (LSCC) by lentivirus mediated RNA interference. MMP-9-RNAi-lentivirus and the
      control lentivirus (GFP-lentivirus) were transfected into Hep-2 cells. Gelatin
      zymography showed the proteins expression of MMP-9 were knockdown in the MMP-9
      siRNA transfected Hep-2 cells. The invasive activity and viability of MMP-9 siRNA
      treated Hep-2 cells were decreased than the control cells measured with modified
      Boyden chamber assay and MTT assay. In animal experiment, 20 nude mice bearing
      Hep-2 cell tumor were randomly separated into the experimental and the control
      groups. The former were intratumorally injected with MMP-9-RNAi-lentivirus, and
      the later were injected with equivalent dose of GFP-lentivirus. Results showed
      the average weight and volume of tumor in MMP-9-RNAi-lentivirus treated group
      were significantly lower than those in the control group (P < .01). The protein
      expressions of MMP-9 were downregulated in tumors of MMP-9-RNAi-lentivirus
      treatment. The PCNA index was obviously lower in the tumors of treated group than
      that in the control group (P < .01). These results suggest that MMP-9 gene
      silence by lentivirus mediated RNA interference can inhibit invasion and growth
      of LSCC.

PMID- 19093257
TI  - Correlation analysis of HOX, ErbB and IGFBP family gene expression in ovarian
      cancer.
AB  - Utilizing microarray gene expression data in cancer research possesses the
      ability to identify deregulated cellular pathways involved in malignant
      development. This study investigated the relationships of three gene families,
      HOX, ErbB and IGFBP, with regard to the development of ovarian cancer. These
      families were of interest because of similar chromosomal locations and their
      deregulated expression in ovarian cancer. Higher level statistics were used to
      differentially analyze microarray data in 65 ovarian samples to assess
      correlation and relationships among the gene families of interest. Fifteen genes
      in the three families were found to be significantly deregulated. Thirty-eight
      significant correlations were found within and between the genes of interest. Our
      data indicates that the significantly modeled relationships between HOX, ErbB and
      IGFBP gene pairs could provide insight into the underlying biological mechanisms
      in ovarian cancer.

PMID- 19093258
TI  - Arterial infusion chemotherapy in patient with repeated recurrent tumor of cecal
      cancer: report of a case.
AB  - PURPOSE: We report a patient with a repeated recurrent tumor after Right
      hemicolectomy for advanced cecal cancer who was treated by intra-arterial
      infusions of 5-fluorouracil (5-FU). METHODS: A computed tomography scan revealed
      a pelvic mass involving the psoas major muscle and quadratos lumborum muscle, in
      contact with the widely projecting toward L2-S2. The fluorodeoxyglucose-positron
      emission tomography (FDG-PET) revealed an accumulation spot in the same place.
      This case was deemed in operable, and one-shot bolus of 5-FU was administered
      through the tumor feeding arteries: the left 3rd, 4th lumbar, and ilio -- lumbar
      arteries at a dosage of 250 mg/body from each artery. RESULTS: A partial
      regression of the tumor was observed by computed tomography. The serum level of
      carbohydrate antigen 19-9 returned normal in 8 months. During chemotherapy, the
      side effect and complications were tolerable, and she experienced only grade-1
      nausea caused by 5-fluorouracil. CONCLUSION: A long-time, intra-arterial 5
      fluorouracil infusion could control effectively and safely.

PMID- 19093259
TI  - Ki67 and salivary cancer.
AB  - We examined Ki67 expression in salivary malignancies of 75 patients with a follow
      up period of up to 20 years. Correlations between enhanced Ki67 and enhanced p53
      and TUNEL and heparanase staining levels were significant. Median survival for
      reduced-stained-tumor patients (< or = 5%) was 163 months, dropping significantly
      to 39 months (p = 0.0005) for enhanced stained tumors (> 5%); 5 year survival
      probability was 93% and 33%, respectively, 45% and 16%, respectively, (p =
      0.0005) at 20 years. Significant correlation between poor survival and
      concurrently altered expression rates of Ki67 and p53, p27 Skp2, TUNEL and
      heparanase in the salivary malignancies indicates a biological role in salivary
      cancer pathogenesis.

PMID- 19093260
TI  - Tumor-infiltrating lymphocytes predict response to neoadjuvant chemotherapy in
      patients with breast carcinoma.
AB  - Tumor-infiltrating leukocytes and other immunohistochemical parameters were
      evaluated in pretherapeutic biopsies and resection specimens in 73 patients
      undergoing neoadjuvant chemotherapy with doxorubicin and paclitaxel. Ten patients
      with pathological complete response had significantly higher p53 expression,
      CD3(+) lymphocyte and CD83(+) cell counts, and lower progesterone receptor
      expression. In the remaining 63 patients, a significant decrease in the
      percentage of Ki-67, vascular endothelial growth factor expression, CD68(+)
      monocytes, and increased CD31(+), CD34(+), and SMA(+) stromal vessels, maximal
      CD3(+) and CD56(+) lymphocyte, maximal and mean CD83(+) cell, maximal CD1a(+),
      and maximal and mean S100(+) cell counts were observed after neoadjuvant
      chemotherapy.

PMID- 19093261
TI  - MG-132 inhibits telomerase activity, induces apoptosis and G(1) arrest associated
      with upregulated p27kip1 expression and downregulated survivin expression in
      gastric carcinoma cells.
AB  - Ubiquitin-proteasome pathway (UPP) is the major system for the selective
      degradation of cellular proteins that play key roles in cellular processes.
      Previous study indicated that ubiquitin-proteasome inhibitor MG-132 could inhibit
      growth of some carcinoma. However, anti-carcinoma mechanism of MG-132 is unclear.
      Our objective was to investigate mechanisms of growth inhibitory effect of MG-132
      on gastric carcinoma cells. Gastric carcinoma cell SGC-7901 was treated with
      ubiquitin-proteasome inhibitor MG-132. Cell growth suppression was evaluated with
      3-(4,5-dimethylthiazole-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay. DNA
      synthesis was evaluated by (3)H-thymidine ((3)H-TdR) incorporation. Activity of
      telomerase was examined by telomeric repeat amplification protocol (TRAP) PCR
      ELISA. Cell cycle and apoptosis were detected by flow cytometry (FCM). DNA
      fragment analysis was used to confirm the presence of apoptosis. Expression of
      p27kip1 and survivin was detected using the western blot method. After exposed to
      MG-132, the growth and value of (3)H-TdR incorporation of gastric carcinoma cells
      were obviously inhibited. TRAP PCR-ELISA showed that light absorption of cells
      gradually decreased after exposed to 5 microM of MG-132 for 24, 48, 72 and 96 h
      (P < 0.01). The percentage of cells at G(0)/G(1) phase was increased and that at
      S and G(2)/M phase was decreased (P < 0.01). The ratio of apoptotic cells treated
      with 5 microM MG-132 for 96 h was 53.7 +/- 6.4%. Agarose electrophoresis showed
      marked ladders. Moreover, expression of p27kip1 of cells was increased and
      expression of survivin was decreased. Our results suggest that MG-132 inhibits
      telomerase activity, induces apoptosis and G(1) arrest which is associated with
      upregulated p27kip1 expression and downregulated survivin expression in gastric
      carcinoma cells.

PMID- 19093262
TI  - Primary systemic therapy in breast cancer: past lessons and new approaches.
AB  - Primary systemic therapy (PST) is a common treatment strategy used to optimize
      surgical outcomes for women with locally advanced breast cancer. Several
      cooperative group trials have shown equivalent survival outcomes between
      neoadjuvant and adjuvant chemotherapy and have identified pathologic complete
      response (pCR) as a biologic marker for survival. Research efforts to optimize
      PST include the development of strategies to predict individual response and to
      guide the choice of chemotherapy. These emerging approaches are informed by our
      knowledge of subtypes of breast cancer, as well as genomic technologies, such as
      chemosensitivity signatures. Following definitive surgery, the management of
      residual disease is controversial.

PMID- 19093263
TI  - Information systems for cancer research.
AB  - The last decade has seen a massive growth in data for cancer research, with high
      throughput technologies joining clinical trials as major drivers of informatics
      needs. These data provide opportunities for developing new cancer treatments, but
      also major challenges for informatics, and we summarize the systems needed and
      potential issues arising in addressing these challenges. Integrating these data
      into the research enterprise will require investments in (1) data capture and
      management, (2) data analysis, (3) data integration standards, (4) visualization
      tools, and (5) methods for integration with other enterprise systems.

PMID- 19093265
TI  - Peer difficulties in children with epilepsy: association with seizure,
      neuropsychological, academic, and behavioral variables.
AB  - PURPOSE/OBJECTIVE: A developmental psychopathology framework was used to examine
      variables associated with peer problems in children with epilepsy (CWE).
      Variables commonly associated with peer difficulties in typically developing
      children, such as inattentive behavior, anxious behavior, and academic
      achievement were investigated. Neuropsychological functioning, age at epilepsy
      onset, and seizure status were also examined. RESEARCH METHOD/DESIGN:
      Participants were 173 CWE, ages 8-15. Structural equation modeling (SEM) was used
      to determine which variables predicted peer problems in CWE and to test
      hypothesized interrelations among variables. RESULTS: The SEM revealed that
      anxious behavior mediated relations between neuropsychological functioning and
      peer difficulties and seizure status and peer difficulties. Inattentive behavior
      mediated the association between neuropsychological functioning and peer
      difficulties. Neuropsychological functioning mediated the relation between age at
      epilepsy onset and inattentive behavior, anxious behavior, and academic
      achievement. CONCLUSIONS/IMPLICATIONS: As seen with typically developing
      children, inattentive and anxious behaviors are related to peer difficulties in
      CWE. Neuropsychological functioning, age at epilepsy onset, and seizure status
      are indirectly associated with peer difficulties; therefore, these variables are
      important to examine in CWE who are experiencing peer problems.

PMID- 19093266
TI  - Lactoferrin and cancer disease prevention.
AB  - Lactoferrin (LF) is an iron-binding glycoprotein that is composed of the
      transferrin family and is predominantly found in the products of the exocrine
      glands located in the gateways of the digestive, respiratory, and reproductive
      systems, suggesting a role in the non-specific defence against invading
      pathogens. Additionally, several physiological roles have been attributed to LF,
      namely regulation of iron homeostasis, host defence against infection and
      inflammation, regulation of cellular growth, and differentiation and protection
      against cancer development and metastasis. These findings have suggested LF's
      great potential therapeutic use in cancer disease prevention and/or treatment,
      namely as a chemopreventive agent. This review looks at the recent advances in
      understanding the mechanisms underlying the multifunctional roles of LF and
      future perspectives on its potential therapeutic applications.

PMID- 19093267
TI  - Chemistry and health of olive oil phenolics.
AB  - The Mediterranean diet is associated with a lower incidence of atherosclerosis,
      cardiovascular disease, and certain types of cancer. The apparent health benefits
      have been partially attributed to the dietary consumption of virgin olive oil by
      Mediterranean populations. Most recent interest has focused on the biologically
      active phenolic compounds naturally present in virgin olive oils. Studies (human,
      animal, in vivo and in vitro) have shown that olive oil phenolics have positive
      effects on certain physiological parameters, such as plasma lipoproteins,
      oxidative damage, inflammatory markers, platelet and cellular function, and
      antimicrobial activity. Presumably, regular dietary consumption of virgin olive
      oil containing phenolic compounds manifests in health benefits associated with a
      Mediterranean diet. This paper summarizes current knowledge on the physiological
      effects of olive oil phenolics. Moreover, a number of factors have the ability to
      affect phenolic concentrations in virgin olive oil, so it is of great importance
      to understand these factors in order to preserve the essential health promoting
      benefits of olive oil phenolic compounds.

PMID- 19093268
TI  - Physiology and genetics of Listeria monocytogenes survival and growth at cold
      temperatures.
AB  - Listeria monocytogenes is a foodborne pathogen that can cause serious invasive
      human illness in susceptible patients, notably immunocompromised, pregnant women,
      and adults > 65 years old. Most human listeriosis cases appear to be caused by
      consumption of refrigerated ready-to-eat foods that are contaminated with high
      levels of L. monocytogenes. While initial L. monocytogenes levels in contaminated
      foods are usually low, the ability of L. monocytogenes to survive and multiply at
      low temperatures allows it to reach levels high enough to cause human disease,
      particularly if contaminated foods that allow for L. monocytogenes growth are
      stored for prolonged times under refrigeration. In this review, relevant
      knowledge on the physiology and genetics of L. monocytogenes' ability to adapt to
      and multiply at low temperature will be summarized and discussed, including
      selected relevant findings on the physiology and genetics of cold adaptation in
      other Gram-positive bacteria. Further improvement in our understanding of the
      physiology and genetics of L. monocytogenes cold growth will hopefully enhance
      our ability to design successful intervention strategies for this foodborne
      pathogen.

PMID- 19093269
TI  - Baobab food products: a review on their composition and nutritional value.
AB  - Several authors have published about baobab food products. Data on
      macronutrients, micronutrients, amino acids, and fatty acids were collected from
      literature for pulp, leaves, seeds, and kernels of the baobab tree. The results
      show that baobab pulp is particularly rich in vitamin C; consumption of 40 g
      covers 84 to more than 100% of the Recommended Daily Intake (RDI) of pregnant
      women (19-30 years). The leaves are particularly rich in calcium (307 to 2640
      mg/100 g dw), and they are known to contain good quality proteins with a chemical
      score of 0.81. The whole seeds and the kernels have a relatively high lipid
      content, 11.6 to 33.3 g/100 g dw and 18.9 to 34.7 g/100 g dw, respectively. The
      pulp and leaves exhibit antioxidant properties with a higher activity in the pulp
      than in the leaves. Reported nutrient contents of different baobab parts show a
      large variation, which may have arisen from various factors. Three
      recommendations are given for future research: 1. More attention should be given
      to accuracy and precision of analytical methods, 2. Research about digestibility
      and bioavailability of baobab products is needed, 3. The effect of storage and
      processing on the nutritional value of baobab products needs to be assessed.

PMID- 19093270
TI  - Investigation of the presence of inorganic micro- and nanosized contaminants in
      bread and biscuits by environmental scanning electron microscopy.
AB  - A European project called "Nanopathology" allowed to develop a new diagnostic
      tool through which the presence of inorganic particulate matter in pathological
      human tissues of the digestive tract could be shown. This unexpected evidence
      induced the authors to put forward the hypothesis that that sort of contamination
      was present in ingested food. In order to demonstrate this hypothesis, 86 samples
      of wheat bread and 49 of wheat biscuits from 14 different countries were analyzed
      by means of an Environmental Scanning Electron Microscopy to detect inorganic,
      micro-, and nano-scaled contaminants. The X-ray microprobe of an Energy
      Dispersion Spectroscope was employed to identify their chemical composition. The
      results indicate that 40% of the samples analyzed contained foreign bodies as
      ceramic and metallic debris of probable environmental or industrial origin.
      Because of the great variety of chemical composition of the particulate matter,
      those contaminants were listed according to the most expressed element. The
      majority of these debris are not biodegradable, some are chemically toxic, and
      none of them have any nutritive value. The work discusses the possible origin of
      such a pollution and the role that it can play on human life.

PMID- 19093271
TI  - Food ellagitannins-occurrence, effects of processing and storage.
AB  - Interest in ellagitannins and ellagic acid has increased over the past few years
      due to its properties as a micronutrient. Ellagitannins are complex plant
      polyphenols composed of hexahydroxydiphenoyl moieties esterified to a sugar.
      Fruits (especially berries and nuts) are rich sources of ellagitannins and
      ellagic acid, a hydrolytic product of ellagitannins. These secondary metabolites
      give the characteristic taste to the fruits and their products, and also play an
      important role in food processing. This paper reviews research about occurrence
      in foods, change during process, and antioxidant activity of ellagitannins and
      ellagic acid.

PMID- 19093272
TI  - Impact of visual impairment on service and device use by individuals with
      diabetic retinopathy.
AB  - PURPOSE: This study was performed to assess the use of devices and caregiving
      among individuals with diabetic retinopathy and to evaluate the impact of visual
      acuity on use. METHODS: Data were collected using a questionnaire that included
      items on demographic and clinical characteristics and on the use of services,
      assistive devices, and caregiving. The study was approved by an institutional
      review board. Two ophthalmologists identified and invited patients with diabetic
      retinopathy and provided best corrected visual acuity (BCVA). Patients provided
      informed consent. De-identified data were analysed in SAS(R). RESULTS: Of the 806
      respondents, 55% were women; mean age was 65 years. Respondents were classified
      into five categories based on BCVA. Few respondents used services such as
      transportation and counseling, but there was wide use of assistive devices. More
      than 20% of respondents used a cane, a hand-held magnifier, and/or special
      glasses. The mean number of devices used increased significantly as BCVA
      deteriorated, as did hours of caregiving. Annual costs for services, devices, and
      caregiving increased as BCVA deteriorated. CONCLUSIONS: There are substantial
      differences in the use and costs of assistive devices and caregiving among
      individuals with diabetic retinopathy with varying BCVA.

PMID- 19093273
TI  - To what extent are family members and friends involved in physiotherapy and the
      delivery of exercises to people with stroke?
AB  - PURPOSE: To examine the views of people with stroke, their 'family
      members/friends' and physiotherapists on the role of the family in physiotherapy
      and the delivery of exercises following stroke. METHODS: A self-report
      questionnaire was administered to 100 'family members/friends' and 75 people with
      stroke. Two focus groups were conducted with 10 expert physiotherapists working
      in the area of stroke rehabilitation. RESULTS: Family members of people with
      stroke are willing to participate in the delivery of unsupervised exercises in
      the hospital and the home setting (n = 91). Furthermore, this is also acceptable
      to people with stroke (n = 65) as an adjunct to routine physiotherapy.
      Physiotherapists highlighted a number of factors that influenced participation in
      physiotherapy such as; level of interest and motivation of the family (n = 5),
      availability (n = 3) and importance of education (n = 2). 'Family
      members/friends' identified reasons that would also limit participation such as
      work commitments (n = 24), lack of confidence (n = 20) and unsuitable treatment
      times (n = 13). The expert practitioners outlined a number of areas that family
      involvement can have an impact, such as treatment carry-over, assisting the
      family unit to cope on discharge and improving handling skills. CONCLUSIONS: Our
      study identifies an under-utilised role for 'family members/friends' in the
      rehabilitation of people with stroke. Family mediated exercises can maximise the
      carry-over outside formal physiotherapy giving patients the opportunity for
      informal practice. This study highlights the need to examine the value of a
      structured programme of exercises that can be delivered to people with stroke by
      their 'family members/friends'.

PMID- 19093274
TI  - Item analysis of the functional status assessment of seniors in the emergency
      department.
AB  - PURPOSE: To report some psychometric properties of the functional status
      assessment of seniors in the emergency department (FSAS-ED) at item level. This
      40-item tool addresses the person's functional status prior to and following the
      decision to consult in ED. METHOD: A sample of 150 community-living elderly
      individuals who consulted the ED was recruited. Two evaluators administered the
      FSAS-ED in the ED and scored it independently. Three measurement properties were
      considered relevant for the item analysis: response distribution, inter-rater
      reliability and the ability to indicate a change between before and following the
      decision to consult ED. Criteria related to these properties were established to
      classify items as being excellent, acceptable or weak. RESULTS: The response
      distributions were excellent or acceptable for 36 items (90%). Results pertaining
      to inter-rater reliability showed 39 excellent or acceptable items (97.5%).
      Comparison of the responses between before and following the decision to consult
      to ED showed 24 (60%) excellent or acceptable items and 16 (40%) weak items; the
      latter were related to communication and cognitive skills. CONCLUSIONS: At the
      item level, the FSAS-ED provides reliable and clinically relevant information
      about the functional status of older adults consulting ED.

PMID- 19093275
TI  - Recovery after stroke: a 1-year profile.
AB  - PURPOSE: To document the course of recovery in a group of first stroke patients,
      with stroke of moderate severity, over a 1-year period. Evaluation of recovery is
      important for estimating rehabilitation needs. METHOD: One-year observational
      study of 23 acute first stroke patients. Recovery was assessed at 15 specific
      intervals using measures of impairment, activity, social participation and
      quality of life. RESULTS: There were significant changes in impairment (p < 0.05)
      and motor disability over 1 year (F ratio = 75.627, d.f. = 4, p < or = 0.0001)
      including the period between 6 and 12 months though recovery did appear to slow
      down after a 9-week 'turning point'. Significant improvements in social
      participation were also seen between 6 and 12 months (p = 0.0021). Quality of
      life did not change and patients' quality of life scores indicated levels of
      'severe distress' at 6 (57.8 [8.8]) and 12 months (58.9 [8.6]). CONCLUSIONS:
      Recovery after stroke was detectable beyond 6 months using detailed measures.
      This demonstration of late recovery has therapeutic implications. An increased
      understanding of the course of recovery following stroke could provide a basis
      for evaluating the varied aspects of therapeutic intervention in stroke
      rehabilitation.

PMID- 19093276
TI  - WHODAS II with people after stroke and their relatives.
AB  - PURPOSE: The present study aimed to measure the internal consistency, inter-rater
      reliability and validity of the World Health Organisation Disability Assessment
      Schedule II (WHODAS II) for its application to stroke patients and their closest
      others. METHOD: Patients were assessed 6 months and 1 year after stroke with the
      self- and proxy-rating versions of the WHODAS II. The modified Rankin Scale (mRS)
      as well as patients' statements about 'Recovery' and 'Independence' were used as
      measurements for validity. Patients' statements concerning individual
      restrictions and limitations were compared with the WHODAS II items. RESULTS:
      Internal consistency can be regarded as good to excellent, inter-rater
      reliability as satisfactory to good. Item reliability ranged from insufficient to
      good, the percentage of agreements was below 80%. WHODAS II scale scores of
      patients with an mRS score of 0 as well as of recovered and independent patients
      differed significantly from others. Correlation coefficients between WHODAS II
      Scales and validation measures ranged from fair to high. Correspondence between
      stroke related problems and WHODAS II items was good. CONCLUSION: The WHODAS II
      is a valid, generally reliable and useful instrument for the assessment of stroke
      patients over the first year after stroke.

PMID- 19093277
TI  - External rotation strength deficit after hip resurfacing surgery.
AB  - PURPOSE: The aim was to assess the effect of resurfacing hip arthroplasty on hip
      muscle function, when, in the posterior approach, the piriformis tendon and outer
      rotators of the hip joint were divided. The unoperated side was used as a
      control. METHODS: Thirty-three consecutive patients (mean age 55 years, 73%
      males) were operated using the posterior approach. Main outcome measures were
      isometric muscle strength of external and internal rotators and extensors of the
      hip and hip pain. RESULTS: Hip external rotation strength (p > 0.001) and leg
      extension strength (p < 0.001) were significantly lower on the operated side
      compared with the un-operated side prior to the surgery. On the operated side
      external rotation strength decreased by 29% (p < 0001) and internal rotation
      strength increased by 28% (p < 0.001). The changes of 12% in leg extension
      strength of the operated side and the changes of 3-10% in all strength
      measurements in the un-operated side were not significant. Three months post
      operatively, the external rotation strength and leg extension strength values
      were 50% and 26% lower (p < 0.001) on the operated side compared with those in
      the un-operated side. The decreases in pain values during the rest, loading as
      well as during the strain of strength measurements were all significant (p <
      0.001). CONCLUSION: Although hip resurfing surgery gives excellent relief of
      pain, significant strength deficit was found in the external rotators 3 months
      post-operatively.

PMID- 19093278
TI  - Maternal input and lexical development: the  case of deaf pre-schoolers.
AB  - BACKGROUND: Mothers facilitate their young hearing children's word learning by
      making reference explicit for novel words through physical designation (e.g.,
      with deictic gestures) and by isolating words in simple syntactic frames. As
      children's language skills develop, such modifications decrease. Less is known
      about hearing mothers' support to their language-delayed deaf children. AIMS: The
      current study investigated whether hearing mothers tailored their input to suit
      their deaf children's word-learning ability as well as their children's word
      knowledge. METHODS & PROCEDURES: Maternal input to 25 oral deaf children was
      examined. Word-learning ability was assessed in an experimental task that tested
      the children's ability to novel map (i.e., infer that a novel word refers to a
      novel object without physical designation). Word knowledge was assessed by
      maternal report. OUTCOME & RESULTS: Mothers whose children did not infer word
      meaning through novel mapping made meaning more explicit than mothers of children
      who could learn through novel mapping. Specifically, these mothers were more
      likely to designate referents physically and use simple syntax. For all children,
      mothers were more likely to make the meaning of novel words more transparent than
      familiar words. CONCLUSIONS & IMPLICATIONS: The results indicate that hearing
      mothers were sensitive to the needs of their deaf children. This sensitivity was
      to children's word knowledge. Mothers seemed aware of what words were in their
      children's lexicon. Mothers did not rely on their children's ability to use novel
      mapping, even for the linguistically advanced children.

PMID- 19093279
TI  - Safety and efficacy of inhaled corticosteroids (ICS) in children with asthma.
AB  - Inhaled corticosteroids (ICS) are the guideline-preferred preventative therapy
      for persistent asthma of all severity levels and for all ages, including
      children. While these drugs are unquestionably efficacious, concerns of adverse
      systemic effects limit patient compliance with treatment regimens and thus the
      attainable benefits. Suppression of bone growth, bone density, and HPA axis
      function, in addition to cataract formation and elevated intraocular
      pressure/glaucoma, have been associated with ICS use. This review will focus on
      recent developments in the safety and efficacy of ICS as compared to oral CS
      corticosteroids and the achievement of a balance between risk and benefit in
      optimizing ICS therapy.

PMID- 19093280
TI  - Secretory phospholipase A2 and airway inflammation and hyperresponsiveness.
AB  - Phospholipases mediate the release of arachidonic acid from membrane
      phospholipids, enabling the subsequent metabolism to potent inflammatory mediator
      products of cyclooxygenase and lipoxygenase enzymes, such as prostaglandins and
      leukotrienes. Cytosolic phospholipase A2 has long been recognized as important,
      but newly characterized are secreted A2 isoenzymes. These secretory
      phospholipases are released into the extracellular compartment on cell
      activation. Elevated levels have been found in allergic patients after allergen
      challenge. Earlier investigations in a mouse asthma model utilizing airway
      challenges with allergen showed an important role for cysteinyl leukotrienes in
      the airway remodeling process. Utilizing secretory phospholipase knockout mice,
      group X deficiency significantly diminished the airway goblet cell metaplasia,
      mucus hypersecretion, increased airway smooth muscle mass, and subepithelial
      fibrosis observed in wild type mice after allergen challenge. The mechanism is
      likely through impaired generation of cysteinyl leukotrienes in the knockout
      mice. Recent human investigation in patients with exercise induced
      bronchoconstriction is supportive of a role of secretory phospholipase, directing
      attention to these enzymes as particularly attractive pharmacologic targets in
      asthma.

PMID- 19093281
TI  - Pharmacokinetics and pharmacodynamics of inhaled glucocorticoids.
AB  - Inhaled corticosteroids are used widely to treat asthma. A number of different
      steroids and inhalation devices are available. The pharmacokinetic and
      pharmacodynamic properties of the different inhaled corticosteroids may influence
      their efficacy and safety profiles. Properties of an ideal inhaled corticosteroid
      include low oropharyngeal deposition, low oral bioavailability, high lung
      deposition, long pulmonary residence times, high receptor affinity, high plasma
      protein binding, and efficient systemic clearance. Attention to these parameters
      might help clinicians optimally balance between the safety and efficacy of
      inhaled corticosteroids in treating individual patients with asthma.

PMID- 19093282
TI  - Role of early-life environmental influences in the development of asthma. How
      painful is it when you catch a bad cold too early?
AB  - A number of studies have implicated lower respiratory tract viral infections
      early in life as a risk factor for the subsequent development of asthma. Despite
      extensive research, the precise molecular mechanisms and pathways by which virus
      infection causes airway inflammation and affects long-term control of airway
      function subsequent to the initial insult remain unclear. Compromised epithelial
      integrity, the elaboration of local pro-inflammatory mediators, and dysfunction
      of neural pathways may all influence airway responses to environmental stimuli.
      Our research has provided evidence that combined neuroimmune interactions primed
      by the virus can initiate and propagate a cascade of events leading to recurrent
      cycles of airway inflammation and obstruction. Nerve growth factor, or NGF,
      represents an ideal link between virus-infected respiratory epithelium and the
      dense subepithelial network of sensory fibers. Studies show that RSV infection
      promotes a large increase in the expression of NGF and its receptors in the
      respiratory tract of rodents and humans. Changes in neurotrophin expression in
      the respiratory tract may coordinate a variety of interactions between sensory
      afferent nerves and multiple components of the immune system and inflammatory
      pathways, thus generating a pathophysiological link between early-life viral
      infections and childhood asthma. Such pathways may provide new avenues for the
      prevention and treatment of asthma and allergy in the near future.

PMID- 19093283
TI  - Individualizing asthma therapy: application of biomarkers.
AB  - New asthma guidelines of National Asthma Education and Prevention Program (NAEPP)
      were released recently with a special emphasis on new information in asthma
      management. The new asthma guidelines emphasize several key terms including
      severity, control, impairment, risk, and responsiveness that are relevant for
      advancing the care of asthma. New directions in asthma research that could
      advance asthma management include early diagnosis and intervention, use of
      combination therapy to achieve asthma control, application of biomarkers and
      genetics to individualize asthma therapy, and the identification of
      immunomodulator therapy to alter the course of the disease. This review will
      discuss the application of biomarkers for asthma management. One biomarker that
      can serve as a prototype for the application of biomarkers to asthma care is
      exhaled nitric oxide (eNO). Initially used as a research tool and now being
      applied in clinical practice, this biomarker has been available for approximately
      10 years. As such, valuable lessons have been learned regarding the advantages
      and limitations of this biomarker for asthma care.

PMID- 19093284
TI  - Severe asthma and its phenotype.
AB  - The phenotype of severe, or difficult, asthma is poorly understood, but recent
      studies have been informative. Factors associated with severe asthma include the
      presence of co-morbidities such as sinusitis, obesity and gastroesophageal
      reflux, poor adherence with prescribed medical regimens, and a severe underlying
      disease process. The worst long-term prognosis in severe asthma is associated
      with the presence of persistent airflow limitation and exacerbations.
      Individualization of therapy based on phenotype is highly recommended.

PMID- 19093285
TI  - Link between childhood asthma and mental health conditions.
AB  - Asthma and mental health conditions often coexist and studies support a link
      between the two disorders. Indeed, an increase in the incidence of depression and
      anxiety has been reported in children with asthma compared to those without
      asthma. Direction of causality in the relationship is unclear. Parental stress
      appears to be an important factor important in the development of infant
      wheezing. There is support for a working hypothesis, linking inner-city violence
      and the development of childhood asthma via pathways that include parental mental
      health conditions, parental nicotine addiction, environmental tobacco smoke, and
      Th2 skewing in infants. It is anticipated that a better understanding of the
      above relationships will lead to the development of new targeted treatment
      strategies for childhood asthma in the future.

PMID- 19093286
TI  - Th-17 cell-related cytokines' potential role in the pathogenesis of severe
      asthma.
AB  - Severe asthma represents a distinct, poorly-understood phenotype of asthma that
      has higher morbidity, mortality and a disproportionate need for health care
      support. Studies have indicated the presence of a specific inflammatory response
      in severe asthmatics, including the paucity of expression of classical Th-2 type
      cytokines. Following antigenic stimulation, naive CD4+ T cells proliferate and
      differentiate into various effector subsets such as Th-1 and Th-2 cells. A third
      subset of CD4+ T cells has recently been identified and designated as Th-17
      cells, which produce IL-17A and F, IL-6, and TNF-alpha. In severe asthma, there
      may be a predominant Th-17 phenotype. These cells may promote the release of
      neutrophil chemotactic factors and induce the expression of GR-beta, which is
      responsible for corticosteroid hyporesponsiveness in immune and structural cells.
      If the role of Th-17 cytokines is confirmed, it might provide a new option in
      controlling this refractory subtype of asthma.

PMID- 19093288
TI  - Reduction of subcutaneous fat and improvement in cellulite appearance by dual
      wavelength, low-level laser energy combined with vacuum and massage.
AB  - BACKGROUND: This study compares the efficacy and safety of low-level, dual
      wavelength laser energy and massage with massage alone for the reduction of
      subcutaneous fat in the thighs of normal women. The device was an early prototype
      of the FDA-cleared SmoothShapes system (Eleme Medical, Merrimack, NH, USA).
      METHODS: The thighs of each individual (n=102) were randomized to either laser
      light (dual wavelength of 650+/-20 nm and 915+/-10 nm) and massage or to massage
      alone (control). Individuals who completed the study (n=74) received a mean of
      14.3 treatments over 4-6 weeks. Magnetic resonance imaging (MRI) scans quantified
      fat pad dimensions before and after the final treatment. RESULTS: Fat thickness
      decreased for the leg treated with laser-massage by 1.19 cm(2) (mean) and
      increased by 3.82 cm(2) (mean) for the control leg over time. The difference was
      statistically significant (p<0.001). Among those who completed the study, 82.26%
      responded to treatment. Individuals reported looser-fitting clothing and
      satisfaction with the procedure and results. Adverse effects were limited to
      occasional increases in urinary frequency. CONCLUSION: Low-level, dual-beam laser
      energy with massage appears to be safe and more efficacious than massage alone
      for reducing subcutaneous fat in the thighs of normal women.

PMID- 19093289
TI  - Measurement of airborne bacteria and endotoxin generated during dental cleaning.
AB  - Dynamic dental instruments generate abundant aerosols in the work environment.
      Dental unit waterlines (DUWL) support a large microbial population and can be a
      significant source of bioaerosols generated during dental treatments. This study
      was conducted to characterize bioaerosol generation during dental treatments
      performed in standardized conditions. Culture-based method (R2A, and blood agar
      with and without O2) and fluorescence microscopy were used. Dental cleaning
      procedures were performed in an isolated treatment room with controlled
      ventilation rate. Andersen microbial samplers were used to collect culturable
      bioaerosols generated before (baseline), during, and after 2 hr of dental
      treatments. Inhalable dust samplers were used to measure total bioaerosols
      content in dental hygienist's and patients' breathing zones. AGI-30 were used for
      the collection of the endotoxin. The use of fluorescence microscopy in
      combination with culture demonstrated that dental staff and patients were exposed
      to up to 1.86 E+05 bacteria/m(3) generated during treatments. Fortunately,
      bioaerosols returned to baseline within 2 hr after the dental procedures. The
      small diameter of the aerosols generated (< 1 microm) suggests that the risk of
      contact between the aerosolized bacteria and the respiratory system of exposed
      individuals is likely to occur.

PMID- 19093291
TI  - Hot flashes and the heart.

PMID- 19093290
TI  - Green tea and statins.

PMID- 19093292
TI  - Ask the doctor. My doctor started me on a calcium-channel blocker for high blood
      pressure. I also take a daily calcium supplement for my bones. Will that
      counteract the drug's effect?.

PMID- 19093293
TI  - Ask the doctor. A friend told me that if you get a stent you can't have bypass
      surgery later on. Is that right? And what about the opposite--getting a stent
      after bypass surgery?

PMID- 19093295
TI  - Trends in the health of young children in California.
AB  - When it comes to school readiness, children's health matters. Healthy children
      are better prepared to learn, concentrate and develop the skills needed to
      succeed in school--and throughout life. Although good health supports learning
      among children of all ages, it is particularly important during early childhood
      when a crucial period of rapid physical and emotional growth occurs between birth
      and age five. Therefore, providing children early on with an environment
      conducive to healthy development and learning lays the foundation for a
      successful future. Not all children, however, have this opportunity. Research
      shows children living in poverty, with poor health status or low-quality
      childcare, are more likely to have developmental and learning delays. Many of
      California's three million children ages 0-5 grow up in environments where their
      health may limit their social, emotional and academic development. This brief
      examines trends in key health indicators for children ages 0-5 in California
      between 2001 and 2005, based on data from the California Health Interview Survey
      (CHIS). Conducted every other year since 2001, CHIS is a statewide survey that
      provides information on health conditions, health behaviors, access to health
      care, and use of services among children, adolescents and adults in California.
      Examining CHIS data from multiple survey years provides valuable information on
      California's progress toward better health and school readiness for young
      children.

PMID- 19093296
TI  - Multilocus analyses reveal involvement of the ESR1, ESR2, and FSHR genes in
      migraine.
AB  - OBJECTIVE: Female hormone genes have been investigated in migraine in recent
      years. Research in this field has been controversial, especially in regard to
      ESR1 gene findings. None of the reports have yet to approach the problem from a
      multigenic point of view. METHODS: We investigated 5 polymorphisms implicated in
      female hormone metabolism (FSHR, CYP19A1, ESR1, NRIP1, and ESR2) in a cohort of
      730 subjects matched for age and sex. The effect of gene-gene interaction was
      assessed using the set association approach, and the corresponding haplotypes
      were studied with PM Plus software. To corroborate initial results, we analyzed
      the selected markers using a cohort of 134 families in which 168 trios were
      suitable for transmission-disequilibrium test (TDT) analysis under the migraine
      with aura (MA) phenotype. RESULTS: A total of 356 consecutive migraine patients
      (198 with MA [76% females] and 158 migraine without aura [MO, 74% females], and
      374 matched controls [71% females]) were genotyped. In the 2-point analyses, the
      ESR1 and ESR2 polymorphisms showed nominal association under MA/MO phenotype, and
      this association was higher with the FSHR polymorphism in MA females (P = .004,
      uncorrected). Using the SUMSTAT program, we observed ESR2-ESR1-FSHR significant
      gene-gene interaction, suggesting association with the MA/MO phenotype (P = .005;
      P = .003 in females), and with MA alone (P = .021; P = .030 for females).We
      corroborated that ESR2-ESR1-FSHR haplotypes interacted for migraine under a model
      free hypothesis (empirical P = .010 for the whole sample; P = .001 for females),
      and the association was stronger for the MA phenotype alone (empirical P = 5.0e
      4, under the heterogeneity model; P = .001 for females). These results were
      corroborated using family-based association approaches. We observed nominal
      association for ESR2 and ESR1 (P = .031 and .034, respectively) in the TDT study,
      and significant association for ESR1 using family-based association test
      statistics. Haplotype-TDT analyses showed further significant gene-gene
      interaction for ESR1-ESR2 (global P = .009), ESR2-FSHR (global P = .011), and
      nominally significant interaction for ESR2-ESR1-FSHR genes (global P = .037).
      CONCLUSION: We found significant association of female hormone metabolism
      polymorphisms under the perspective of multigene approach.

PMID- 19093297
TI  - Interaction of genes from influx-metabolism-efflux pathway and their influence on
      methotrexate efficacy in rheumatoid arthritis patients among Indians.
AB  - OBJECTIVE: Methotrexate (MTX) is the drug of choice for rheumatoid arthritis (RA)
      but is effective only in around 60% of treated patients. Bioavailability of MTX
      may be a major determinant of response status and this may be governed by
      variations in MTX receptor and transporter genes and genes responsible for
      polyglutamation and deconjugation. We investigated the contribution of single
      nucleotide polymorphisms (SNPs) in RFC, FOLR1, FPGS, GGH and MDR1 genes to MTX
      response in RA patients from North India. METHODS: RA patients recruited using
      American College of Rheumatology criteria, were categorized into good and poor
      responders to MTX, based on disease activity score. A total of 17 SNPs from the
      above mentioned genes were genotyped and tested for association with MTX response
      using [chi]2 test; logistic regression along with clinical variables; and gene
      gene interaction using multifactor dimensionality reduction (MDR). RESULTS: One
      novel synonymous SNP Ala324Ala (972 G > A) was identified in RFC gene. The CT
      genotype of C3435T in MDR1 gene conferred almost twice the risk of poor response
      [[chi]2 = 5.85, P = 0.01, odds ratio (95% confidence interval) = 1.97 (1.13
      3.42)] and was retained in binary logistic regression [B = 0.66, P = 0.025,
      adjusted odds ratio (95% confidence interval) = 1.93(1.09-3.42)]. Significant
      interaction between SNPs in GGH and MDR1 genes seems promising. CONCLUSION:
      Interactions between genes coding for deconjugation and transporter seem to be
      important determinants of MTX response in RA but replication and functional
      studies would be confirmatory.

PMID- 19093294
TI  - Evaluation criteria for musculoskeletal and craniofacial tissue engineering
      constructs: a conference report.
AB  - Over the past 20 years, tissue engineering (TE) has evolved into a thriving
      research and commercial development field. However, applying TE strategies to
      musculoskeletal (MSK) and craniofacial tissues has been particularly challenging
      since these tissues must also transmit loads during activities of daily living.
      To address this need, organizers invited a small group of bioengineers, surgeons,
      biologists, and material scientists from academia, industry, and government to
      participate in a two and half-day conference to develop general and tissue
      specific criteria for evaluating new concepts and tissue-engineered constructs,
      including threshold values of success. Participants were assigned to four
      breakout groups representing commonly injured tissues, including tendon and
      ligament, articular cartilage, meniscus and temporomandibular joint, and bone and
      intervertebral disc. Working in multidisciplinary teams, participants first
      carefully defined one or two important unmet clinical needs for each tissue type,
      including current standards of care and the potential impact of TE solutions. The
      groups then sought to identify important parameters for evaluating repair
      outcomes in preclinical studies and to specify minimally acceptable values for
      these parameters. The importance of in vitro TE studies was then discussed in the
      context of these preclinical studies. Where data were not currently available
      from clinical, preclinical, or culture studies, the groups sought to identify
      important areas of preclinical research needed to speed the development process.
      This report summarizes the findings of the conference.

PMID- 19093298
TI  - Colleagues' bad behavior harms patient care.

PMID- 19093299
TI  - Career options for a 'lost nurse'.

PMID- 19093300
TI  - Authors' correction: chrysin is a Passiflora coerulea extract.

PMID- 19093301
TI  - Primary blast injury of the eye.

PMID- 19093302
TI  - Early failure of external fixation.

PMID- 19093303
TI  - The Airtraq laryngoscope in severe ankylosing spondylitis.

PMID- 19093304
TI  - XXII Olomouc Hematological Days with International Participation, 28-30 May 2008,
      Olomouc, Czech Republic. Abstracts.

PMID- 19093306
TI  - Stephen Burke.

PMID- 19093305
TI  - [Forensic experts' evaluations of madness in French courts, 1821-65].

PMID- 19093307
TI  - A Welsh life, a medical life: Dr. Emyr Wyn Jones (1907-1999) interviewed.

PMID- 19093309
TI  - "A good idea of colonial life": personal letters and Irish migration to New
      Zealand.

PMID- 19093310
TI  - [The destiny of French rice enterprises in the Mekong Delta].

PMID- 19093312
TI  - The Argyll Robertson pupil 1869-1969. A critical survey of the literature.

PMID- 19093313
TI  - Zero positive surgical margins after radical prostatectomy: is the end in sight.
AB  - Positive surgical margins represents incomplete resection by the surgeon, and the
      elimination of positive margins represents the only clinical feature during
      radical prostatectomy that can lead directly to improved cancer outcomes. The
      introduction of new robot-assisted technology and technical refinements has led
      to declines of positive surgical margins. Although margins induced by incomplete
      cancer resection by the surgeon have been reduced for organ-confined disease, the
      'Holy Grail' of zero margins is not yet attainable in prostatectomy, and is more
      problematic in cancer that has penetrated beyond the prostate. Intraoperative
      frozen biopsies are imprecise. The union of real-time optical coherence
      tomography technology of the da Vinci robotic platform for identification of
      positive margin sites, and technical advances with wider excisions during surgery
      may provide promise for further reduction of surgical margins to zero.

PMID- 19093315
TI  - Abstracts of the 21st Annual Scientific Meeting of the Hong Kong Neurological
      Society, 15-16 November 2008.

PMID- 19093314
TI  - Re-evaluation of the age at death of immature fossil hominids.
AB  - We report here revised chronological ages at death of immature fossil hominids
      demonstrating for the first time that Plio-Pleistocene hominids had markedly
      abbreviated growth periods relative to modern man, similar to those of the modern
      great apes. Previous estimates of age at death for fossil hominids have
      principally been based on dental eruption, maturation and dental wear criteria
      for modern man and hence reflect their age in 'human' years. We are now able to
      estimate the absolute duration of permanent incisor crown formation by observing
      gross incremental growth features in enamel and thereby apply a timescale to
      dental developmental events for specimens representing four Plio-Pleistocene
      fossil hominid taxa. Thus we have derived more reliable-species-specific
      estimates of age at death that provide a more secure model on which to base
      studies of the palaeodemography, growth and maturation of early hominids.

PMID- 19093316
TI  - Treatment strategies in mild asthma.
AB  - PURPOSE OF THE REVIEW: More than 10 years ago the category of mild asthma was
      split into mild intermittent and mild persistent asthma and maintenance therapy
      with low dose inhaled corticosteroids (ICS) was recommended for mild persistent
      asthma. The threshold for instituting regular ICS therapy was arbitrarily chosen,
      in the absence of clinical studies specifically addressing this issue. RECENT
      FINDINGS: The results of recent trials have questioned the assumption that all
      patients at the mild end of the asthma severity spectrum should be committed to
      regular anti-inflammatory treatment with inhaled corticosteroids. As a
      consequence, the identification of the relevant outcomes for the treatment of
      mild persistent asthma has become a matter of discussion, which has provided the
      rationale to test the efficacy and well tolerance of new strategies, other than
      guidelines-recommended regular low-dose ICS, for the treatment of mild persistent
      asthma. SUMMARY: Several approaches have been evaluated with some promising
      results, to include the combination of ICS and long-acting b2-agonists, oral
      leukotriene antagonists, and the intermittent or as-needed use of ICS in the
      absence of regular treatment. Conversely, little effort has been made to evaluate
      therapeutic options other than as-needed bronchodilation in mild intermittent
      asthma.

PMID- 19093320
TI  - Abstracts of the 14th Pediatric Rheumatology European Society Congress, 5-9
      September 2007, Istanbul, Turkey.

PMID- 19093319
TI  - From research to development to implementation: challenges in health informatics
      and health information management.

PMID- 19093321
TI  - Heparin.

PMID- 19093322
TI  - Central nervous system vasculitis.
AB  - PURPOSE OF REVIEW: In the past decade, primary and secondary central nervous
      system (CNS) vasculitides have been more commonly diagnosed and recognized than
      previously. With the increasing awareness of these disorders, it is crucial for
      the treating physician to differentiate between causes of CNS vasculitis and to
      recognize their marked clinical and pathophysiological heterogeneity. This review
      focuses on the major forms of primary CNS vasculitis, as well as secondary CNS
      vasculitis with emphasis on their clinical findings, diagnoses, and treatment.
      RECENT FINDINGS: The proposal of reversible cerebral vasoconstriction syndromes
      (RCVS) as a unifying concept for a group of disorders which are characterized by
      acute-onset severe recurrent headaches, with or without additional neurologic
      signs and symptoms, and prolonged but reversible vasoconstriction of the cerebral
      arteries, has been a major breakthrough in this field over the past decade.
      Recognition of this common mimic (i.e. RCVS) has allowed optimal management of a
      sizable group of patients previously confused with pathologically documented CNS
      vasculitis. SUMMARY: Sound treatment decisions are based on accurate diagnosis.
      It is essential for the clinicians involved in the evaluation of patients with
      CNS vasculitis to be aware of its mimics especially RCVS. This article provides a
      comprehensive review of CNS vasculitis and its differential diagnosis.
      Furthermore, it touches upon workup and treatment of CNS vasculitis.

PMID- 19093323
TI  - Environmental tobacco smoke exposure and child behaviors.
AB  - RATIONALE: Emerging evidence suggests that exposure to environmental tobacco
      smoke (ETS) may be linked with behavior problems in childhood, but previous
      research has relied primarily on parent report of exposure, and results are
      inconclusive. OBJECTIVES: To investigate the relationship between exposure to ETS
      and child behavior problems among children with asthma. METHODS: The sample
      included 220 children who were enrolled in an asthma intervention trial and
      regularly exposed to ETS at home. Serum cotinine was used to measure exposure to
      tobacco smoke, and behavior problems were assessed by parent report on the
      Behavior Assessment System for Children. Covariates in adjusted analyses
      included: sex, age, race, asthma severity, asthma medication, maternal education,
      prenatal tobacco exposure, maternal depression, and Home Observation for
      Measurement of the Environment score. RESULTS: Child behavior problems increased
      with increasing exposure to ETS. A stratified analysis of boys and girls
      separately indicated higher exposure among girls, but behavior problems were
      statistically significantly associated with exposure only in boys. Increasing
      behavior problems included externalizing behavior problems (beta= 2.23, p =.02)
      such as hyperactivity and aggression, internalizing behavior problems (beta=
      2.19, p= .01) such as depression, and behavior symptoms (beta= 2.55, p= .01).
      CONCLUSIONS: Among children with asthma, exposure to ETS is related to increased
      child behavior problems among boys.

PMID- 19093324
TI  - Transplantation.

PMID- 19093325
TI  - Sarcoidosis and the rheumatologist.
AB  - PURPOSE OF REVIEW: The purpose of this review is to discuss challenges in the
      diagnosis and treatment of sarcoidosis by rheumatologists. RECENT FINDINGS:
      Sarcoidosis is a heterogeneous multisystem granulomatous disease. Rheumatologists
      are faced with multiple challenges in the management of this disease. Features
      that can have similarities to many rheumatic diseases are being increasingly
      reported. There are many reports of sarcoidosis coexisting with or mimicking
      rheumatic diseases such as systemic lupus erythematosus, rheumatoid arthritis,
      and ankylosing spondylitis. Musculoskeletal features of sarcoidosis can also
      mimic infection and malignancy. Biomarkers for the diagnosis and monitoring of
      treatment of response are lacking. Tumor necrosis factor (TNF) inhibition therapy
      is a viable alternative for immunodulation for various manifestations. However,
      increased vigilance is needed, as there are also emerging reports of drug-induced
      sarcoidosis in association with the use of anti-TNFalpha agents and other
      medications. This article reviews these diagnostic and treatment challenges that
      rheumatologists face. SUMMARY: Many questions remain to be answered. More studies
      looking at the reliability of certain serological and radiological biomarkers are
      needed. Issues concerning the safety of the use of biological response modifiers
      in inducing sarcoidosis need further study.

PMID- 19093326
TI  - Difficult temperament, breastfeeding, and their mutual prospective effects: the
      Norwegian Mother and Child Cohort Study.
AB  - OBJECTIVE: (1) To examine the extent to which difficult temperament and
      breastfeeding are associated at child age 6 and 18 months. (2) To examine
      longitudinally whether breastfeeding has an influence on temperament development
      or whether difficult temperament has an influence on continued breastfeeding.
      METHOD: This prospective study is part of the Norwegian Mother and Child Cohort
      Study, which targets all women giving birth in Norway; the present sample
      comprises 30,466 children. Mothers reported on child difficult temperament at
      child age 6 and 18 months and on breastfeeding from 0 to 6 months and from 6 to
      12-14 months. Prospective associations between breastfeeding and difficult
      temperament were examined using structural equation modeling, with comparison of
      cross-lagged pathways. All analyses were adjusted for background variables that
      are relevant for breastfeeding. RESULTS: At 6 months, children with more
      difficult temperament were significantly less likely to have been "fully"
      breastfed (exclusively and predominantly breastfed) for the recommended period of
      6 months (unadjusted point-biserial correlation r pb = -.15; adjusted r pb = 
      .11). At 12 to 14 months, there was no longer an association between difficult
      temperament and (continued) breastfeeding after adjusting for background
      variables, temperament, and breastfeeding at 6 months. The cross-lagged analyses
      of the longitudinal pathways yielded negligible effects of difficult temperament
      on later breastfeeding and of breastfeeding on later temperament. CONCLUSION:
      Difficult temperament and reduced breastfeeding seem to be associated only during
      the first half-year of the child's life. After that, we found no evidence of
      codevelopment between difficult temperament and breastfeeding.

PMID- 19093327
TI  - Obesity and the musculoskeletal system.
AB  - PURPOSE OF REVIEW: To describe recent developments highlighting the effects and
      mechanisms of obesity and weight loss on the musculoskeletal system. RECENT
      FINDINGS: The global epidemic of obesity has far-reaching effects on the
      musculoskeletal system and associated conditions such as osteoarthritis,
      rheumatoid arthritis, spondyloarthropathy, and fibromyalgia. Obesity increases
      the need for, and reduces the health outcomes from, joint replacement surgery,
      which has enormous implications for societal economic burden. New insights have
      been gained into the possible mechanisms by which obesity is associated with
      musculoskeletal disease incidence, symptom severity and treatment outcomes
      particularly for osteoarthritis. Research exploring the role of adipocytokines
      provides a novel possible metabolic link for these diseases. SUMMARY: Obesity has
      a significant impact on the musculoskeletal system being associated with both
      degenerative and inflammatory conditions. Future research assessing the effects
      of obesity and weight loss as well as further elucidating the action of
      adipocytokines will aid in the assessment and management of this increasingly
      prevalent condition.

PMID- 19093328
TI  - Fetus-saving Caesarian rejection by pregnant woman: a case study.

PMID- 19093329
TI  - Intraocular lens centration and stability: efficacy of current technique and
      technology.
AB  - PURPOSE OF REVIEW: The manuscript presents a review of recently published studies
      analyzing different methodologies to assess centration and stability of
      intraocular lenses after implantation. RECENT FINDINGS: Considering that there is
      no current gold standard for centration and stability of intraocular lenses after
      implantation, we have summarized the different techniques used clinically for
      intraocular lenses centration and stability estimation. We have described the use
      of Scheimpflug imaging, the anterior segment optical coherence tomography and
      photography analysis used for lens position estimation. Techniques used to assess
      lens rotation are based on image analysis on digital retroillumination images.
      SUMMARY: Centration and stability of intraocular lenses are a matter of most
      importance and many methods have been developed. It seems that the best method
      for the assessment of lens position considers Scheimpflug imaging and for
      stability the use of retroillumination images.

PMID- 19093330
TI  - Optical coherence tomography and cataract surgery.
AB  - PURPOSE OF REVIEW: To provide an unstructured review of the recent literature on
      the role of optical coherence tomography (OCT) in cataract surgery with specific
      focus on cystoid macular edema (CME) on the basis of expert opinion of the
      authors. RECENT FINDINGS: OCT appears to be a useful method to reveal clinically
      relevant postsurgical CME and is complementary to fluorescein angiography. A
      majority of eyes demonstrate minimal increases in postoperative retinal thickness
      after cataract surgery on OCT, though those eyes that do develop clinically
      relevant CME show substantial increases. Using at least 40% increase in retinal
      thickness from baseline on OCT may be a valid, objective, and uniform method of
      defining CME. Preoperative and postoperative OCT evaluations in selected eyes at
      high risk (diabetes, uveitis) for CME may be warranted. SUMMARY: OCT has become a
      useful diagnostic tool to assess CME after cataract surgery.

PMID- 19093331
TI  - Surgical competency in residents.
AB  - PURPOSE OF THE REVIEW: To review the literature for recent work that will help
      educators develop programs to produce residents who are competent cataract
      surgeons. RECENT FINDINGS: Medical educators feel increasing pressure from the
      Accreditation Council for Graduate Medical Education (ACGME) to emphasize
      competence in our residency program graduates. Residency program director and
      resident graduate surveys show problems in our ability to produce cataract
      surgeons competent in all areas. The resident surgery learning curve increases
      the risk of complications in early cases. Several recent papers address
      curriculum development, which may be of interest to cataract teachers and program
      directors. Assessment of surgical skill continues to be an area of interest and
      has prompted some interesting work. The use of simulation with wet laboratories
      and computer devices is of increasing interest in an effort to hasten the
      learning curve. SUMMARY: An organized surgical curriculum with defined
      expectations using simulation and assessment tools will help residency programs
      meet ACGME mandates. A competent resident in cataract surgery will have to
      develop skills in all of the six ACGME competencies. Several recent articles
      address these issues.

PMID- 19093332
TI  - Living on the edge: health care expenses strain family budgets.
AB  - Affordability of medical care is a central focus of health care reform efforts.
      As health care costs continue to increase and the economy declines sharply, there
      is very little cushion in family budgets for health care costs, even for families
      with insurance coverage. Financial pressures on families from medical bills
      increase sharply when out-of-pocket spending for health care services exceeds 2.5
      percent of family income, according to a new national study by the Center for
      Studying Health System Change (HSC). Low-income families and people in poor
      health experience financial pressures at even lower levels of spending, largely
      because they have already accumulated large medical debts they are unable to pay
      off. Many Californians also incur substantial burdens from health care expenses,
      although the rate of medical bill problems is somewhat lower in California
      compared with the overall United States. Extended interviews with a select number
      of families facing problems with medical bills provide additional detail on how
      families are forced to make difficult trade-offs with other family necessities,
      put off paying other bills, cut down on other expenses and delay getting needed
      medical care

PMID- 19093333
TI  - Myelodysplastic syndromes: disease overview and therapy options.
AB  - The increase in new cases of myelodysplastic syndromes is likely attributable to
      both an aging population and a greater number of cancer survivors who have
      received chemotherapy. A detailed diagnostic history is critical in order to
      place a patient in the proper treatment category.

PMID- 19093334
TI  - Multiple myeloma: epidemiology and therapeutic options.
AB  - Myeloma remains an incurable disease, but its management has significantly
      improved with the introduction of novel treatment agents. Variations in both
      disease manifestation and patient response to treatment have personalized
      approaches to care.

PMID- 19093335
TI  - Balancing the policy with appropriate patient care.
AB  - Major changes are underway at CMS that may affect practices among health plans
      and providers. If implemented, these changes could alter the delivery of cancer
      care.

PMID- 19093336
TI  - Understanding tumor profiling and assessing treatment.
AB  - Gene expression profiling allows us to look into a tumor cell to see how genetic
      information is communicated and affects cell behavior. Data gathered during the
      development of the 70-gene assay (MammaPrint) set the stage for future assay
      development. Recently, a 21-gene assay (Oncotype DX) was recommended by ASCO and
      NCCN as a standard of care for newly diagnosed, stage 1 or 2, node-negative,
      estrogen-receptor-positive breast cancer patients.

PMID- 19093338
TI  - Encourage your patients to participate in community clinical research.

PMID- 19093337
TI  - A health plan's integration of molecular diagnostics and the impact on treatment
      pathways for quality care.
AB  - This Mid-Atlantic area Blues plan views genetic biomarkers as an important
      advancement in predicting recurrence rates and response to chemotherapy in
      estrogen-receptor-positive, node-negative, HER2-negative women with early-stage
      breast cancer. Care-First's Pay for Quality oncology program strives to combine
      clinically sound treatment with stable outcomes and predictable costs.

PMID- 19093339
TI  - Cutting edge yet close to home. Cancer research in the community.

PMID- 19093340
TI  - What makes a community clinical research program successful?

PMID- 19093341
TI  - Manage cardiac side effects of cancer treatment.

PMID- 19093342
TI  - Learn about clinical trials in your own community.

PMID- 19093343
TI  - Translational research: How what's learned at the bench gets to the bedside.

PMID- 19093344
TI  - Deciphering telomerase structure raises hope for new cancer treatments.

PMID- 19093345
TI  - Final consensus regarding APRN regulation is released.

PMID- 19093346
TI  - ONS offers a variety of support for nurses conducting community research.

PMID- 19093347
TI  - Children must come first.

PMID- 19093348
TI  - What can healthcare professionals learn from the case of Baby P?

PMID- 19093349
TI  - How well are England's urgent care services performing?

PMID- 19093350
TI  - Show me my cancer. Interview by Carol Davis.
AB  - Enabling young patients to see pictures of their cancer cells leads to a more
      positive outlook and increases feelings of control over their condition.

PMID- 19093351
TI  - Focus on the 'can do'. Interview by Charlie Callanan.
AB  - New benefit arrangements for people with disabilities are designed to reduce the
      number of people deemed 'unfit for work' and increase opportunities to get back
      into the workforce.

PMID- 19093352
TI  - An unpopular view. Interview by Adele Waters.
AB  - The author of a controversial study that suggested nurses give preferential care
      to favoured patients, believes the profession needs to understand better the
      dynamics that determine therapeutic relationships.

PMID- 19093353
TI  - Forgive and survive.

PMID- 19093354
TI  - Opening the gate.

PMID- 19093355
TI  - Give a little respect.

PMID- 19093356
TI  - Learning in clinical practice: the importance of peers.
AB  - AIM: To explore whether nursing students learn from each other and, if so, how,
      when and where this learning takes place. METHOD: An interpretive ethnographic
      qualitative research study of a group of pre-registration nursing students (n =
      15). Participant observation was the primary tool of data collection. Students
      gave their consent to be observed in classroom and clinical environments
      throughout the three years of the pre-registration programme. Data took the form
      of audio-taped conversations with and between students together with field notes.
      A thematic analysis was undertaken to reveal the student experience of peer
      learning. FINDINGS: The importance of friendships to clinical learning for
      students was apparent in three respects: friendships and learning in clinical
      practice, survival skills and developing clinical skills. The students talked
      about their friendships being strong and enduring and enabling learning to take
      place. The students used their peers as a resource to pass on survival skills and
      help each other to learn how to be a nurse. Students also taught each other a
      variety of clinical skills. Traditional notions of seniority were challenged
      because the students appeared more concerned with what their peers had
      experienced. CONCLUSION: Friendships were an important aspect of peer learning
      for the students in this study and, more importantly, friendship fostered
      learning. Peer learning in clinical practice is an informal and underestimated
      aspect of clinical learning and is valued by students.

PMID- 19093357
TI  - Mobile phone technology in chronic disease management.
AB  - Mobile phones are being used to improve nurse-patient communication and monitor
      health outcomes in chronic disease. Innovative applications of mobile technology
      are expected to increase over time in community management of cancer, heart
      disease, asthma and diabetes. This article focuses on mobile phone technology and
      its contribution to health care.

PMID- 19093358
TI  - Understanding depression in palliative and end-of-life care.
AB  - Depression in patients receiving palliative and end-of-life care is difficult to
      distinguish from grief and sadness. However, there are some important
      distinctions and it is a clinical condition that is treatable and should not be
      considered a necessary or normal part of the dying process. This article examines
      the nature of depression and describes the stress vulnerability model of
      depression, linking it to recent developments in the neurobiology of depression.
      It also discusses how to distinguish depression from other symptoms that patients
      may be experiencing.

PMID- 19093359
TI  - Clostridium difficile.

PMID- 19093360
TI  - Learning on the go.

PMID- 19093361
TI  - Trust built on shared power.

PMID- 19093362
TI  - First and last impressions.

PMID- 19093363
TI  - [Effect of GABA-positive drugs on the background and superior sagittalis sinus
      electrostimulated activity of neurons in the nucleus trigeminalis caudalis of
      rats].
AB  - There is extensive clinical evidence for the high efficacy of GABA-ergic drugs in
      prophylactic and abortive treatment of migraine and cluster headache, while the
      mechanisms of anticephalgic drugs action are not clear, in particular, because of
      insufficient number of investigations on experimental headache models. In this
      study, the influence of baclofen (i.v.) in doses 2.5, 5, 10, and 15 mg/kg and
      valproate (i.v.) in doses 25, 50, 100, and 200 mg/kg on the background activity
      of the trigeminal nucleus caudalis neurons and that evoked by electrical
      stimulation of the superior sagittalis sinus was investigated in series of acute
      experiments on rats. It is established, that baclofen and valproate reduce both
      the background and evoked activity of trigeminal complex neurons in dose
      dependent manner, thus determining the role of GABA-A and GABA-B receptors in
      realization of this effect. These results provide experimental basis for
      explanation of the clinical efficacy of the GABA-positive drugs in vascular
      headaches.

PMID- 19093364
TI  - [Effects of heptapeptide selank on the content of monoamines and their
      metabolites in the brain of BALB/C and C57Bl/6 mice: a comparative study].
AB  - The effect of heptapeptide selank on the content of neurotransmitter monoamines
      and its metabolites in the brain structures of BALB/C and C57Bl/6 line mice under
      conditions of the open-field test were studied. Significant interstrain
      differences in the content of norepinephrine (NE), dopamine (DA), serotonin (5
      HT) as well as in the levels of their metabolites in hippocampus, hypothalamus,
      striatum and frontal cortex of C57Bl/6 and BALB/C mice were demonstrated. In
      particular, the content of 5-HT and its metabolite 5-oxyindolacetic acid (5-HIAA)
      in hippocampus of BALB/C mice (with passive stress response) was higher than in
      the same structure of C57Bl/6 (stress-susceptible) animals. The injection of
      selank (0.3 mg/kg) led to an increase in the NE level in the hypothalamus of both
      mice strains. At the same time, selank produced opposite effects on the content
      of DA metabolites: the concentrations of dioxyphenylacetic (DOPAC) and
      homovanillic (HVA) acids were found to increase in frontal cortex and hippocampus
      of C57Bl/6 mice, while the same parameters in BALB/C mice were demonstrated to
      decrease. Selank induced a decrease in 5-HT and 5-HIAA levels in the hippocampus
      of BALB/C mice, but did not affect these parameters in C57Bl/6 animals. The
      obtained results are indicative of selectivity of the anxiolytic effects of
      selank.

PMID- 19093365
TI  - [Effects of zatebradine on the course of experimental myocardial infarction under
      long-term treatment conditions in rats].
AB  - A long-term (21 days) administration of the specific bradycardic agent
      zatebradine to rats with experimental myocardial infarction led to a decrease in
      the intensity of necrotic changes in the cardiac muscle as evaluated from the ECG
      recorded QS complex incidence rate. Morphological studies provided evidence for
      reduced intensity of the dystrophic processes in myocardium. Under these
      conditions, the drug did not affect the pump and contractile heart functions. At
      the same time, zatebradine normalized the reaction of mean aorta blood flow
      acceleration to volume load (which was inhibited at myocardial infarction), that
      is, prevented the development of latent heart failure. Zatebradine restored the
      infarction-decreased norepinephrine (NE) level in cardiac muscle and increased NE
      content in hypothalamus and brainstem. Along with that, the ratios of
      deoxyphenylacetic acid/dopamine and homovanillic acid/dopamine were reduced.

PMID- 19093366
TI  - [Effects of digoxin and corglycon on ion currents in neuronal membrane of snail
      (Lymnaea stagnalis)].
AB  - The results of endocellular dialysis membrane potential monitoring show that
      cardiac glycosides digoxin and corglycon in concentration from 10(-12) to 10(-6)
      M influence the sodium, calcium and potassium ion currents in isolated snail
      (Lymnaea stagnalis) neurons in reversible and slightly dose-dependent manner. In
      low concentration (10(-12) - 10(-8) M) both substances increased all ionic
      currents by up to 5%, while in higher concentrations both drugs led to the
      suppression of ion currents. The most pronounced decrease (up to 26% relative to
      control) was observed for sodium ion current under the action of digoxin in a
      concentration of 10(-6) M. The process of slow potassium currents inactivation
      was accelerated by corglycon in a concentration of 10(-6) M. Digoxin caused a
      shift in the current - voltage curve maximum by 5 - 10 mV to the right on the
      potential axis. Generally, digoxin in comparison to corglycon produced less
      activating and more suppressing effect on the membrane ion currents studied.

PMID- 19093367
TI  - [Hypotensive effect of oxatriazolium-5-olate derivative].
AB  - Intravenous administration of azasidnon-6 (oxatriazolium-5-olate derivative)
      induces prolonged dose-dependent decrease in arterial blood pressure in awake
      Wistar and SHR rats. Hypotensive effects of azasidnon-6 in SHR rats is
      significantly higher during inhibition of endogenous NO synthesis.

PMID- 19093368
TI  - [Effect of phytopreparation Narcophyt on choleretic reaction in white rats with
      experimental hepatitis].
AB  - Experiments on white rats show that the phytopreparation Narcophyt possesses
      choleretic activity. In rats with experimental hepatitis induced by ethanol, the
      course of therapeutic and prophylactic administration of Narcophyt favorably
      influenced the bile secreting function of the liver, accelerated bile secretion,
      stimulated the synthesis and secretion of cholates, as well as the secretion of
      bilirubin and excretion of cholesterol. The cholagogic effect of Narcophyt was
      comparable with that of the reference drug cholosas.

PMID- 19093369
TI  - [Effect of Filipendula ulmaria extract on immune system of CBA/CaLac and C57Bl/6
      mice].
AB  - Extract of Filipendula ulmaria (L.) Maxim administered intragastrically in doses
      10, 50, 150 and 500 mg/kg stimulated both inductive and productive phases of the
      humoral immunity response in CBA/CaLac and C57BL/6 mice. The extract also
      exhibited pronounced antiinflammatory effect, which was manifested by a decrease
      in the synthesis of interleukin-2 by splenocytes and by suppression of
      proinflammatory cytokines production in delayed-type hypersensitivity reaction.
      At the same time, Filipendula ulmaria extract did not influence the functional
      activity of peritoneal macrophages.

PMID- 19093370
TI  - [Antiallergic effect of D-glucuronic acid].
AB  - The influence of D-glucuronic acid (course administration) on a Thl and Th2
      immune response was studied. It is established that D-glucuronic acid suppressed
      Th2-dependent immune response as it decreased the lethality from the anaphylactic
      shock, abolished the local anaphylactic reaction and strongly inhibited allergen
      specific IgE and IgG1 production. In addition, D-glucuronic acid stimulated Thl
      dependent immune response since it enhanced the delay-type hypersensitivity
      reaction, increased amount of antibody-forming cells and the number of antibodies
      in blood. It is concluded that the mechanism of the antiallergic effect of D
      glucuronic acid is related to a change in the Th1/Th2 balance in favor of Th1.

PMID- 19093371
TI  - [Effects of phytoecdysteroids and bemithyl on functional, metabolic, and
      immunobiological parameters of working capacity in experimental animals].
AB  - Influence of phytoecdysteroids (isolated from Ajuga turkestanica) and bemithyl on
      the duration of swimming of laboratory animals (mice, rats) under various
      experimental conditions was studied. Turkesteron and cyasteron increased duration
      of dynamic work carried out by animals, decreased fatigue, and accelerated
      recovery processes to a greater extent that did bemithyl. The positive influence
      of phytoecdysteroids on the working capacity is based on the activation of
      metabolic processes in skeletal muscles, directed to support the homeostasis of
      energy production. Phytoecdysteroids also accelerate recovery of immune reactions
      which are decreased due to the exhausting physical work.

PMID- 19093372
TI  - [Proliferative activity of rat skin fibroblasts under the action of
      glucocorticoids and gestagens].
AB  - Temporal and concentration dependences of the effect of the new synthetic
      gestagen 17alpha-acetoxy-3beta-butanoyloxy-6-methyl-pregna-4,6-dien-20-one (ABMP)
      and reference glucocorticoids (dexamethasone and hydrocortisone) and progesterone
      on the proliferative activity of rat skin fibroblasts were examined using the MTT
      assay. The results demonstrated that ABMP along with glucocorticoids produced an
      antiproliferative action against fibroblasts, with the maximum (38%) suppression
      of the metabolic activity of cells observed after 5-day incubation at a drug
      concentration of 10(-5) M.

PMID- 19093373
TI  - [Mechanisms of the therapeutic effect of immunoglobulins in the treatment of
      bronchial asthma].
AB  - Data on the therapeutic effectiveness of intravenous injections of
      immunoglobulins in high doses in patients with bronchial asthma are analyzed.
      Some possible mechanisms of this therapeutic effect are considered, which are
      related to of immunoglobulin fragments capable of interacting with cytochrome P
      450 and NO-synthase systems of the liver.

PMID- 19093374
TI  - [Mechanisms of the antipsychotic effect of neuroleptics: problem state of the
      art].
AB  - Well-known and recent data on the neurochemical and neurophysiological mechanisms
      of the antipsychotic action of typical and atypical neuroleptic drugs are
      summarized.

PMID- 19093375
TI  - [Vascular effects of ginseng compounds].
AB  - In the review it has been systematized data on the vascular effects of
      ginsenosides in vivo. It has been shown that ginsenosides increase a tolerance of
      isolated arteries to oxidative stress, hypoxia-reoxigenation, homocysteine and
      other pathogenic factors. It has been performed an analysis published works on
      the effects of triterpene saponines on the NO synthesis in the isolated
      endothelial cells, a proliferation of these cells, an apoptosis of
      endotheliocytes, a secretion of vascular endothelial growth factor by endothelial
      cells. It was exhibited data on the potency of ginsenosides to inhibit a
      proliferation of vascular smooth muscle cells. It has been discussed a molecular
      mechanisms of triterpene saponines action, their interaction with steroid hormone
      receptors, proteinkinases, NO-synthase, guanilyl cyclase, K(Ca)-channels, Ca(2+)
      channels.

PMID- 19093377
TI  - Rat doctors.

PMID- 19093376
TI  - [NSAID-induced gastropathy and its prophylaxis].
AB  - Data on the frequency of NSAID-induced gastropathy, its pathogenesis, risk
      factors, and the principal ways of prevention are reviewed.

PMID- 19093378
TI  - The tenacity of tuberculosis.

PMID- 19093379
TI  - AIDS-related lymphomas: the Rhode Island experience.

PMID- 19093380
TI  - Management of behavioral problems in dementia.

PMID- 19093381
TI  - Variations in laboratory testing during medical clearance of psychiatric patients
      in the emergency department.

PMID- 19093382
TI  - Prognostication: medicine's lost art.

PMID- 19093383
TI  - Health risks among Rhode Island high school students, 1997-2007.

PMID- 19093384
TI  - Smoking in theatrical productions.

PMID- 19093385
TI  - Business, gifts and boundaries in the physician patient relationship.

PMID- 19093386
TI  - The apocalyptic prefix.

PMID- 19093387
TI  - ODA patient's page. Wisdom teeth.

PMID- 19093388
TI  - How going digital will affect the dental office.
AB  - BACKGROUND AND OVERVIEW: The impact of digital imaging on dental practice depends
      upon the degree of planning conducted before implementation. Digital technologies
      have the potential to improve diagnosis; facilitate patient treatment procedures;
      and streamline storage, transfer and retrieval. These technologies also provide
      for secure backup of patients' image data, critical to re-establishing the
      practice should fire, flood or earthquake occur. CONCLUSIONS: The decision to
      invest in digital radiographic equipment should be a simple one for dental
      practitioners. Although digital x-ray sensors have long equaled analog film for
      diagnostic tasks, they have several advantages over film radiography, including
      immediate image production with solid-state devices; interactive display on a
      monitor with the ability to enhance image features and make direct measurements;
      integrated storage with access to images through practice management software
      systems; security of available backup and off-site archiving; perfect
      radiographic duplicates to accompany referrals; security mechanisms to identify
      original images and differentiate them from altered images; the ability to tag
      information such as a patient identifier, date of exposure and other relevant
      details; and interoperability of the Digital Imaging and Communications in
      Medicine file format. CLINICAL IMPLICATIONS: Most clinicians should contemplate
      integrating, at a minimum, intraoral digital x-ray sensors and a digital
      panoramic system into their practices.

PMID- 19093389
TI  - Are we really doing anything about the future of healthcare?

PMID- 19093391
TI  - Mixed signals. Highlighting potential dangers of RFID in hospitals. Interview by
      Alan Joch.

PMID- 19093390
TI  - Removing the "shield" that minimizes new patient flow.

PMID- 19093392
TI  - Count on a backup.

PMID- 19093393
TI  - The bright side of energy conservation.

PMID- 19093394
TI  - Much ado about RFID.

PMID- 19093395
TI  - Best practices target pressure ulcers.

PMID- 19093396
TI  - Factors to consider during operating room construction.

PMID- 19093397
TI  - A radical idea.

PMID- 19093398
TI  - Finances. Economy takes a toll on hospitals; credit ratings continue to slide.

PMID- 19093399
TI  - Philanthropy. In tight economic times, former patients become the focus of
      fundraising.

PMID- 19093400
TI  - Regulation. IRS seeks more information on bad debt, community benefit.

PMID- 19093401
TI  - Infection control. New paint could combat MRSA, other superbugs.

PMID- 19093402
TI  - Voices. Why palliative care matters to patients and to your bottom line.
      Interview by Bill Santamour.

PMID- 19093404
TI  - Working around technology.

PMID- 19093403
TI  - Should cell phones be banned?

PMID- 19093405
TI  - Accreditation. New challenger takes aim at the Joint Commission.

PMID- 19093406
TI  - Medicaid. Cuts to Medicaid inpatient payments loom.

PMID- 19093407
TI  - CMS' stealth health reform. Plan to reduce readmissions and boost the continuum
      of care.

PMID- 19093408
TI  - The disappearing primary care physician.
AB  - They are the cornerstone of any effort to reduce health care costs and improve
      care, but many would-be primary care docs are choosing to become specialists
      instead. Can hospitals and others find ways to reverse this disturbing and
      dangerous trend?

PMID- 19093409
TI  - Are you ready for RAC?

PMID- 19093410
TI  - Mammography rebounds.

PMID- 19093411
TI  - On the spot when doc is not.

PMID- 19093412
TI  - The nurse and patient safety.
AB  - Nurses are the key to hospital efforts to improve patient safety. This foldout
      section examines Transforming Care at the Bedside and other initiatives designed
      to help nurses become safety leaders.

PMID- 19093413
TI  - A dangerous bind for American workers.

PMID- 19093414
TI  - Linking public accountability to quality improvement.

PMID- 19093415
TI  - Supporting change.

PMID- 19093416
TI  - Caring for heart failure patients and their families: directions for research.

PMID- 19093417
TI  - A "basket of care" for heart failure patients managing at home: evaluating a
      community-based nursing intervention from a patient's perspective.
AB  - BACKGROUND: Patients with heart failure (HF) in the community represent a large
      and growing patient population whose complex care requires implementation of
      innovative care modalities. The Centre Hospitalier--Centre de Sante et de
      Services Sociaux--Corridor of Service for Heart Failure Patients (CH-CSSS-CSHFP)
      represents a novel approach to address the challenges of delivering comprehensive
      care to HF patients in the community. PURPOSE: In this study, the researchers
      aimed to answer the question: What is the patient's perception of care received
      in the CH-CSSS-CSHFP? METHOD: A descriptive qualitative design and semistructured
      interviews guided the inquiry. SAMPLE: A convenience sample (n=5) of HF patients
      was recruited from five community health centres. RESULTS: Themes that arose from
      analysis included "Staying home": A shared goal of the patient and service,
      "Checking on": Health-related monitoring, and "Being connected": Ties to the
      health care system. CONCLUSION: Results of this study provide insight into the
      patient's unique perspective on how this service has impacted his/her HF
      management and may assist health care professionals in designing more effective
      community-based services.

PMID- 19093418
TI  - Provider perceptions of implementation of integrated care pathways for patients
      with chronic heart conditions.
AB  - Integrated care pathways (ICPs) for atrial fibrillation and congestive heart
      failure have been examined in the literature. Systematic study, however, of
      provider experiences with implementation of pathways for these conditions is
      lacking. Given the pivotal role of nurses in the care of these chronic heart
      conditions, this information may be valuable for cardiovascular nurses who use
      pathways for these chronic heart conditions. In this study, qualitative methods
      were used to systematically examine providers' experiences with the
      implementation of integrated care pathways for these conditions. Nurses,
      physicians, and pharmacists provided feedback on their experiences. Analyses
      revealed that pathways were perceived by providers to have strengths (e.g.,
      improved communication, knowledge, transition, patient involvement and review),
      but also multiple challenges (e.g., education, timelines, complexity, interest,
      ownership, coordination, and documentation) when implemented for these complex
      chronic medical conditions. Provider recommendations for pathway implementation
      with these conditions are shared in this study. This information may facilitate
      cardiovascular nurses in implementing ICPs in other centres.

PMID- 19093419
TI  - The nature of telephone nursing interventions in a heart failure clinic setting.
AB  - BACKGROUND: There is a lack of published data about the nature of nursing
      interventions that are required to provide telephone management for patients with
      heart failure (HF). PURPOSE: The nature of patient issues, telephone nursing
      interventions, and associated workload at one HF clinic are described in this
      study. METHODS: Workload was captured using a computerized workload measurement
      tool. An electronic telephone log categorizing nursing interventions as providing
      education, changing medication doses, ordering diagnostic tests and consulting
      with community health care providers, and the scope of practice required to
      complete the intervention was kept. RESULTS: Nurses spent 24% of their working
      hours doing 1914 telephone visits in one year. Medications were changed 583 times
      and diagnostic tests were ordered 207 times. Nurses initiated 65% of calls;
      others were received from patients, family members, and other health care
      providers. CONCLUSION: A combination of nurse practitioners and registered nurses
      with medical directives can address the issues that commonly arise through
      telephone management of HF patients.

PMID- 19093420
TI  - Natriuretic peptides: putting the evidence into practice.
AB  - With advances in cardiovascular medicine, people are living longer with
      cardiovascular disease. There is an increased incidence and prevalence of heart
      failure. Misdiagnosis of heart failure, particularly in the early stages, is not
      uncommon. Natriuretic peptides (BNP and NT-proBNP) have been established to be of
      additional value to the clinical examination in heart failure diagnosis and
      management. As frontline caregivers for heart failure patients, nurses should be
      aware of the clinical use of these peptides either as a complementary diagnostic
      test for heart failure or as a possible therapeutic modality.

PMID- 19093421
TI  - The potential of nursing to reduce the burden of heart failure in rural Canada:
      what strategies should nurses prioritize?
AB  - Chronic heart failure (CHF) is an increasingly common condition in high-income
      countries that has a large and negative impact on life quality and expectancy,
      and is associated with high financial costs. In Canada, CHF has an especially
      large impact on rural settings because of the higher proportion of older adults
      (aged >65 years) in these settings, and because care and outcomes tend to be more
      adverse in rural parts of the country compared to urban settings. Much can be
      done to reduce these burdens in terms of pharmacological, behavioural and health
      service strategies. However, rural patients tend to have worse care and outcomes
      than urban patients. Realizing the benefits of these strategies in Canada's rural
      settings requires consideration of underlying reasons for poor care and outcomes.
      We propose the main reasons for adverse outcomes are related to the nature of CHF
      and the combined influence of demographics, health services and the rural
      context. Nurses remain under-used in CHF management in Canada and can play a
      vital and influential role in reducing the burden of CHF in rural settings. To
      increase and improve nurses' roles, we recommend that nurses should support the
      development and adaptation of disease management programs in rural settings and
      promote the centrality of nursing in these programs. Nurses in or working with
      rural settings should seek to support and use tele-health technologies
      effectively and provide better support to lay caregivers. It will also be vital
      to increase the nursing capacity regarding specialist roles for CHF management.

PMID- 19093422
TI  - [The experience of couples when the woman has heart failure].

PMID- 19093423
TI  - Systematic review coupled with meta-analysis regarding the clinical follow-up
      programs of congestive heart failure (CHF) patients.

PMID- 19093424
TI  - Cultivating trust: the board-medical staff relationship.
AB  - To achieve better quality and safety outcomes, boards and their medical staffs
      must overcome a relationship often fraught with tension and distrust in order to
      forge a new partnership.

PMID- 19093425
TI  - Home sweet medical home.
AB  - In response to multiple crises in U.S. health care, the medical home model has
      proliferated, with the potential to attract primary care physicians, save money
      and boost quality and patient satisfaction.

PMID- 19093426
TI  - Trends and strategic planning: implications for the board.

PMID- 19093427
TI  - Five ways to think about patient safety.
AB  - Health care organizations committed to long-term patient safety improvement need
      to find new ways to think about their leadership, systems, strategies, culture
      and behavior.

PMID- 19093428
TI  - Hospital strategy in the current credit crisis: 7 must-do-actions.
AB  - Hospitals need to take seven "must-do" actions to survive the capital markets
      crisis.

PMID- 19093429
TI  - Be an advocate for your community.

PMID- 19093430
TI  - Accountability for community benefit.

PMID- 19093431
TI  - Determination and discrimination of intraspecific diversity of Astragalus
      gossypinus by eco-phytosociological method from west of Iran.
AB  - Astragalus gossypinus Fischer with wide distribution in Iran belongs to the genus
      Astragalus (Fabaceae). According to existing references and information,
      individuals of this species are present in many stations with different
      ecological conditions. This study carried out for determination and
      discrimination of intraspecific diversity of Astragalus gossypinus by Eco
      phytosociological method from west of Iran. In this method, the principle of data
      collecting and analyzing based on floristical composition (as floristical
      markers) of each Endogenous milieu (as the unit of study in Eco-phytosociological
      method). In this order, application of Endogenous milieu (special station) for
      data collecting and then their analyzing permit us only determine existence of
      inter and intraspecific diversity. Then for determinating kind and level of
      intraspecific diversity (Ecophene, Chemotype, Cytotype, Ecotype ...), can use
      other studies such as: morphological, anatomical, phytochemical, cytological and
      etc. In this survey, 29 special stations were studied and 195 species
      distinguished as companions for Astragalus gossypinus. Then floristic-ecologic
      data collected from each 29 special stations and analyzed by Anaphyto software
      (F.C.A, A.H.C, B.O, Marquag methods). Comparison of obtained results on multiple
      coordinate axes from F.C.A method with results from B.O, Marquag and A.H.C
      methods led to determination of 7 main groups of Endogenous milieus (special
      station). Flavonoid analyses were used for determinating kind and level of
      intraspecific diversity in 7 discriminated groups. Leaves flavonoid components of
      all collected individuals of Astragalus gossypinus were investigated by TLC
      method. Obtained data from flavonoid survey analyzed by SPSS and MVSP package
      with WARD and UPGMA methods. Finally, the results of flavonoid studies confirmed
      the same 7 groups that identified by floristical composition study and showed
      intraspecific diversity in chemotype level. So according to these results, we can
      introduce 7 chemotypes for Astragalus gossypinus from west of Iran. These
      chemotypes exist in different stations with various ecological conditions.

PMID- 19093432
TI  - Heritability and correlation for nitrogen (N2) fixation and related traits in
      peanut (Arachis hypogaea L.).
AB  - The objectives of this study were to estimate broad sense heritability for N2
      fixation and related traits and agronomic traits and evaluate correlations among
      these traits. Seventy four progenies in the F, generation previously selected in
      the F4 generation for high and low performance for N fixation and related traits
      were tested for N2 fixation and related traits and their agronomic performances.
      A non-nodulating line was also included as a reference crop for nitrogen
      determination. The experiment was carried out under limited soil nitrogen
      conditions. A randomized complete block design with four replications was used.
      Data were recorded for leaf color score, nodule dry weight, top dry weight, fixed
      nitrogen, pod number, pod weight, seed weight, seed size, shelling percentage and
      harvest index. Most heritability estimates for N2 fixation and related traits
      were moderate and high ranging from 0.33 to 1.00 except one low estimate (0.33).
      Most heritability estimates for agronomic traits were also moderate and high
      ranging from 0.37 to 1.00 except two low estimates (0.37 and 0.50). High
      heritability estimates in the F5 generation indicated that genetic variations of
      this population after divergence selection in the F4 generation are conserved and
      further selection for N2 fixation and agronomic traits in this population is
      possible when individual characters are considered. High and positive
      correlations among fixed nitrogen and its components were found indicating that
      increase in one trait can increase others. Correlations between N2 fixation and
      pod yield were low and varied depending on crosses suggesting that selection for
      both N2 fixation and pod yield is essential.

PMID- 19093433
TI  - Gender and maturation differences in health-related physical fitness and physical
      activity in Turkish children.
AB  - The aim of this study was to assess health - related physical fitness and
      physical activity parameters among children and to determine whether there were
      any significant gender and maturation differences. A total of 853 Turkish school
      children comprised of male prepubertal (n=212), female prepubertal (n=199), male
      pubertal (n=222) and female pubertal (n=218) children selected from the suburban
      schools of the Anatolian district of Istanbul were enrolled into this study. The
      health-related physical fitness properties included body composition, muscular
      strength, elasticity and aerobic fitness test and measurements. For estimation of
      the level of physical activity and daily energy expenditure the Bouchard's 3 day
      activity record was employed. The intensity of physical activity was divided into
      three groups with those having a MET of less than 4 considered sedentary, those
      with MET of 4-7 light while those with of MET >7 were considered to have Moderate
      Vigorous Physical Activity (MVPA). The univariate 2 (gender) X 2 (maturation)
      ANOVA and co-variance tests were used to compare group means for body
      composition, physical fitness and physical activity. Evaluation of body fat ratio
      of the children revealed a significantly higher value for girls. The Max VO2 and
      handgrip strength was greater in the male gender while maturation differences
      showed a similar pattern favoring the pubertal period. The flexibility of the
      pubertal girls was significantly better than their male counterparts. The
      duration of physical activity was significantly longer in the males than female
      children. The duration of light activity among girls was longer than that of boys
      whereas the duration of MVPA in boys was significantly longer than that of girls.
      On the other hand the duration of MVPA among the prepubertal children was
      significantly higher than that of children in the pubertal period.

PMID- 19093434
TI  - Study the effects of different levels of fat and L-carnitine on performance,
      carcass characteristics and serum composition of broiler chicks.
AB  - An experiment was conducted in order to study the effect of 3 levels of fat (1,
      3, 5%) and 2 levels of L-camitine (0 and 250 mg kg(-1)) on 360 male Ross broiler
      chicks in a factorial arrangement (2 x 3) with completely randomized design with
      6 treatments, 4 replicates and 15 chicks in each replicates. All diets were
      isocaloric and isonitrogenous and were fed to chicks from 1 to 42 days of ages.
      During the experiment feed intake, body weight gain and feed conversion ratio
      were measured weekly. Mortality was measured throughout the experiment. At 42
      days of ages 4 birds from each treatment were slaughtered for determination of
      carcass characteristics and serum composition. Data of the experiment were
      analyzed by GLM procedure of SAS. Increasing of fat in the diets significantly
      improved performance of chicks in grower (22 to 42 days) and whole period (1 to
      42 days) of the experiment (p < 0.05). Chicks fed with diets containing 3% fat
      had the highest breast meat and lowest abdominal fat percentage (p < 0.05).
      Adding L-carnitine to diets had not significant effect on performance and carcass
      characteristics. Interaction between fat and L-carnitine was significant on liver
      weight (p < 0.05). The levels of triglyceride (TG) and glucose in blood serum
      were affected by increasing of dietary fat (p < 0.05). Adding L-carnitine to
      diets significantly decreased the level of serum triglyceride, cholesterol and
      VLDL (p < 0.05). Dietary treatments had not significant effect on mortality.

PMID- 19093435
TI  - Ferula gummosa Boiss. Embryogenic culture and karyological changes.
AB  - Ferula gummosa Boiss. a highly valuable medicinal plant which naturally
      propagates in very limited areas of the Middle East with specific environmental
      conditions. The production of Ferula gummosa somatic embryos and the karyological
      analysis of somatic seedlings were the purpose of this study. High frequency
      indirect embryogenesis was induced in callus derived from zygotic embryonic axes.
      Embryogenesis was obtained when callus tissues were placed onto an agar induction
      Murashige and Skoog medium with 1-naphthalene acetic acid and after the transfer
      of the cultures in a thermoperiod regime of 16 h, 19 degrees C/8 h, 7 degrees C
      under photoperiod of 16 h light/8h dark. Embryogenic callus tissues were
      maintained by subculture on induction medium. Globular proliferation was achieved
      with suspension culture in the Murashige and Skoog medium added with 1
      naphthalene acetic acid or 2,4-dichlorophenoxyacetic acid for two weeks.
      Maturation of embryos and development of plantlets arose on the induction agar
      medium, but was better after transfer into the hormone free Murashige and Skoog
      medium. However, the level of abnormal embryos was high. Direct embryogenesis was
      obtained from somatic seedlings. The best results were obtained from hypocotyl
      explants. Embryo induction was achieved by two week culture of the explants in
      2,4-dichlorophenoxyacetic acid liquid medium; somatic embryo growth and
      maturation was recovered on the hormone free medium. High level of abnormalities
      was recorded in the culture. Karyological analysis showed a high incidence level
      of cytochimerism in somatic seedlings with chromosome stickiness, polypoidy and
      aneuploidy in metaphase cells of the same root tip. The frequency of these
      karyological changes varied with the type of somatic embryos with regard to
      morphological abnormalities. Normal and abnormal rooted somatic seedlings were
      able to grow until production of the first leaf and then entered dormancy in the
      same manner as zygotic plantlets.

PMID- 19093436
TI  - Role for leptin and prolactin in human juvenile rheumatic diseases.
AB  - This study was done to evaluate the relation between the level ofleptin,
      prolactin, IL-4 and IL-5 with the activity of Rheumatoid Arthritis (RA) and Lupus
      erythematosus (SLE). The study included 33 patients divided into two groups.
      Group 1 included twenty-one patients with Juvenile rheumatoid arthritis (13 males
      and 8 females) with age 11.9 +/- 3.6 years and twelve patients with systemic
      lupus erythematosus were enrolled as group 2 (2 males and 10 females) with age
      15.8 +/- 2.9 years. Twenty-one healthy children with matched age, sex and
      anthropometrics measures were included in the study to serve as control group
      (group 3). There were significant increases in the levels of Leptin (<0.038),
      Prolactin (p < 0.021) IL-4 (p < 0.005) in Juvenile Rheumatoid Arthritis group
      with insignificant decrease in IL-5 (p < 0.724) in comparison to control group.
      Systemic Lupus group show a significant increase in level of Leptin (p < 0.05),
      Prolactin (p < 0.02) and IL-4 (p < 0.000) with an insignificant increase in IL-5
      (p < 0.685) in comparison to control group. RA patients show a positive
      significant correlation between Prolactin, IL-5 and activity with negative
      insignificant correlation between IL-4 and activity. Where in Lupus patients
      there was a positive significant correlation between Prolactin, IL-4 and activity
      with negative insignificant correlation between IL-5 and activity. There was no
      correlation between Leptin and activity in both diseases (RA, SLE). There's a
      highly significant positive correlation between serum Leptin levels and BMI among
      all patients of RA and Lupus (p < 0.000, p < 0.003), respectively. There was a
      difference in the Leptin level between male and female patients with a
      significant increase in the female than male (p < 0.05). We can conclude from our
      results that Leptin cannot be used to assess disease activity in RA and SLE where
      Prolactin can be used to assess disease activity in RA and SLE.

PMID- 19093437
TI  - Genetic analysis of protein, lysine, gluten and flour yield in bread wheat
      (Triticum aestivum L.).
AB  - The study was carried out to investigate the nature of gene action determining
      the inheritance pattern of protein, lysine, gluten and flour yield in eight wheat
      varieties (Pak 81, Pothowar 93, Parwaz 94, Shahkar 95, Suleiman 96, Chakwal 97,
      Kohistan 97 and MH 97) selected on the basis of phenotypic diversity. In order to
      ascertain the gene action involved in the inheritance of these characters, the
      techniques like analysis of variance of Hayman model and genetic component
      analysis were employed. The estimates of components of genetic variation showed
      that additive genetic effects controlled the expression of traits like protein
      contents and flour yield, however, non-additive gene effects were more important
      for lysine contents and gluten contents. Directional dominance was observed in
      case of protein contents, which indicated the possibility of further improvement
      in this particular trait. Protein contents and flour yield being controlled by
      additive genetic effects with partial dominance suggested that selection could be
      practiced in early segregating generations for improvement in these traits.

PMID- 19093439
TI  - Assessment of the possibility of direct crossing between cultivated potato and
      two wild allotetraploid relatives.
AB  - The cultivated potato Solanum tuberosum L. is an autotetraploid with Endosperm
      Balance Number (EBN) of 4. There are some allotetraploid 2EBN wild species with
      desirable traits for potato improvement. However, it is very difficult to cross
      between these two groups due to differences in EBN. Eleven genotypes of
      autotetraploid cultivated potato including the six cultivars of subsp. Tuberosum
      (tbr) and five clones of subsp. Andigena (adg) were crossed with two wild
      allotetraploid species: S. acaule (acl) and S. stoloniferum (sto). For asses the
      pollen-pistil incompatibility, some ofpollinated flowers were fixed in Carnoy's
      solution and stained with aniline blue. Evaluation with fluorescent microscope
      revealed that pre-zygotic pollen-pistil incompatibility in these crosses is
      frequent. The pistils of both subsp. of cultivated potato were incompatible with
      pollens of acl but when sto used as staminate parent it was compatible with five
      cultivars of subsp. Tuberosum, but incompatible with most ofsubsp. Andigena (4
      clones). From 739, 4x, 4EBN x 4x, 2EBN crosses we couldn't get any viable seed.
      In reciprocal crosses, allotetraploid species were pollinated with a mix of
      pollens from Tuberosum or Andigena clones. The crosses of sto x adg, acl x adg
      and acl x tbr were compatible but in the case of sto x tbr the situation was not
      clear. From these crosses 157 fruits were obtained but most of them contained
      only shrink seed and we find just one hybrid from the sto x tbr combination. The
      hybrid was tetraploid (2n = 4x = 48) and vigorous with profuse flowering and good
      fertility. When this hybrid was used as the pistillate parent it was compatible
      with both parental species.

PMID- 19093438
TI  - Polymorphism of some native Sistan grapes assessed by long and short primers for
      RAPD markers.
AB  - Grapevines have Bronze ages archive in Sistan area of Iran. In order to study the
      genetic variation and taxonomic relationships between 6 cultivars of the Sistan
      grapevines (Vitis vinifera L.) at molecular level, random amplified polymorphic
      DNA (RAPD) markers were used. The data were subjected to statistical analyses and
      genetic resemblance was calculated using Dice similarity index. The grapevines
      related to the different geographic areas of Sistan were assessed by 50 short (10
      mer) and long (15-21 mer) primers. Out of 50 primers which were tested, 21
      primers gave reproducible results. Selected primers created 497 bands. Resulting
      profiles showed that the produced bands varied in size from 300 to 3500 base
      pairs. The numbers of reliable polymorphic fragments for short and long primers
      were 86 and 334 bands, respectively. In multiplication reaction the items in the
      size area of 564 to 1904 base pair resulted for short primers and 564 to 4277
      base pair for long primers. From the bands calculated a matrix that was analyzed
      by the unweighted pair group method on arithmetic averages to draw a dendrogram.
      The population was classified in 4 main groups in which Red Yaghooti and White
      Yaghooti had the maximum and Red Yaghooti and Laal had the minimum similarity
      coefficients. In our study, by comparing the results gained from technique long
      and short primers in RAPD, the potential value of long primers for the production
      ofpolymorphism in grapes was identified.

PMID- 19093440
TI  - Copper toxicity influence on antioxidant enzymes activity in tomato plants and
      role of arbuscular mycorrhizal fungus Glomus etunicatum in the tolerance of
      toxicity.
AB  - Soil microorganisms have been shown to possess several mechanisms capable of
      altering metal bioavailability for uptake into roots. In addition, root
      mycorrhizal associations have been shown to affect the rate of metal uptake.
      There is evidence that exposure of plants to excess concentrations of heavy
      metals such as Cu results in oxidative injury. In this study, effect of
      arbuscular mycorrhizal fungus Glomus etunicatum on tolerance of Cu toxicity in
      tomato plants was studied. In order to prepare seedling medium, we used washed
      and sterilized sand and agricultural soil. Tomato seeds were surface sterilized
      and planted in two pots. One filled just with sterilized sand (for non
      mycorrhizal treatments) and the other filled with sterilized sand mixed with G.
      intraradices mycorrhizal inoculum. We were certain about complete colonization
      after 4 weeks, so we transferred three seedlings to each main pot. Plants grew in
      growth chamber for nine weeks. During growth period plants received modified
      Hoagland's solution (with half P content) with Cu concentration of 0, 1.5, 3.5,
      5.5, 7.5 mM CuSO4 in triplicates. Antioxidant enzymes activity, Ascorbate
      Peroxidase (APX) and Guaiacol Peroxidase (GPX) and Root Length Colonization (RLC)
      percentage in mycorrhizal and non-mycorrhizal plants were measured. APX activity
      in mycorrhizal shoots increased but there was no significant correspondent
      increase in roots of these plants. GPX activity in mycorrhizal roots increased
      but there was no significant correspondent increase in shoots of these plants.
      Activity of this enzyme in roots and shoots of mycorrhizal plantshigher than non
      mycorrhizal plants. Estimation of root length colonizatinon by gridline intersect
      method, increase in Cu concentration, colonization percentage decreased
      significantly. The data show the possible role of mycorrhiza in plant protection
      against Cu toxicity.

PMID- 19093441
TI  - Soluble CD26 and CD30 plasma levels in HIV infected patients with and without GB
      virus type C coinfection.
AB  - GB virus type C (GBV-C) probably influences HIV infection associated disease by
      either directly inhibiting HIV replication or enhancing the immune competence to
      cope with HIV. Still the definitive mechanisms of this inhibitory effect need to
      be identified. To address the possibility of immune modulating effects of GBV-C
      coinfection in HIV patients we evaluated plasma levels of soluble (s) CD26 and
      CD30 in HIV infected patients with and without GBV-C. Cross-sectional comparison
      of sCD26 and sCD30 levels among 6 HIV/GBV-C coinfected, 11 HIV mono-infected and
      13 healthy controls was carried out. We used a commercial EIA to evaluate sCD26
      and scD30 and a RT-PCR assay to detect active GBV-C infection. The Mann-Whitney U
      test was used for statistical analysis. No statistically significant differences
      were observed in levels of sCD26 and sCD30 in plasma of HIV infected patients
      with and without GBV-C viremia. GBV-C infection does not appear to influence the
      sCD26 and sCD30 levels.

PMID- 19093442
TI  - Amiloride inhibition of vacuolar Na+/H+ antiporter enhance salt stress in Zea
      mays L. seedlings.
AB  - The aim of this study to show the importance of salt intracellular
      compartmentation as a tolerance mechanism by inhibition of Na+/H+ antiporter
      system. In this research 4 day/old Zea mays L. seedlings (var. single cross 704)
      were exposed to 200 and 300 mM NaCl with and without 100 and 200 micromolar
      amiloride. After 48 h, the roots and shoots of seedlings were harvested
      separately. The changes of total Na+ absorption, the amount of malondialdehyde
      and the activity of antioxidant enzymes such as guaiacol peroxidase, ascorbate
      peroxidase and catalase were analysed. The results indicated that Na+ absorption
      has been increased by salt stress but was not influenced by amiloride.
      Malondialdehyde content and the activity of antioxidant enzymes such as guaiacol
      peroxidase, ascorbate peroxidase and catalase were increased in salt stressed
      plants specially in plants treated with salt and amiloride. Therefore salt stress
      has caused osmotic and oxidative stress in plants and amiloride as inhibitor of
      vacuolar Na+/H+ antiporter has been increased salt stress. Therefore we concluded
      that Na+ compartmentation in the cell is very important to reduce its damage in
      the cytosol and vacuolar Na+/H+ antiporter has an essential role in Na+
      homeostasis in the cell by exporting excess Na+ to the vacuole.

PMID- 19093443
TI  - Ecological studies on the macrohydrophytes in Egypt II. Ludwigia stolonifera
      (Guill. and Perr.) P.H. Raven.
AB  - The present study contributes information about the environmental factors
      controlling the distribution, variation in standing crop phytomass and chemical
      compositional change of Ludwigia stolonifera. Also, treatment with cattle manure,
      as source of organic waste, was made to evaluate the response of the plant to the
      environmental pollution. The sandy textured bottom sediments of Ludwigia habitat
      at Damira irrigating canal had higher percentages of organic carbon and total
      soluble salts in spring than in the other seasons while the overlying water was
      characterized by low total soluble salts. The phytomass and assimilating surface
      area were increased in spring and summer months and appeared to decline in
      winter. The phytochemical constituents were highly concentrated during August. As
      common in hydrophyte, the plant organs of L. stolonifera are characterized by
      abundance of aerenchyma, absence of cork cells and reduction of vascular tissues.
      Addition of cattle manure to the aquatic habitat of Ludwigia plant resulted in an
      increase of organic carbon, salinity, chloronity and in a decrease of pH value of
      hydrosoil and water. Heavy metals accumulation showed considerable increase due
      to application of cattle manure and this appeared to be a reflection to the
      increased concentrations of these metals in the environment.

PMID- 19093444
TI  - Production and immobilization of alpha-amylase from Bacillus subtilis.
AB  - Alpha-amylase production by Bacillus subtilis was studied under different
      cultivation conditions. The maximum alpha-amylase production occurred after an
      incubation period of 48 h, temperature 40 degrees C and pH 7.5. Among the defined
      carbohydrates, starch (1%) was the best carbon source. The organism grew better
      and produced high levels of alpha-amylase using peptone as nitrogen source. The
      produced alpha-amylase was immobilized on various carriers by different methods
      and the properties of the enzyme were compared before and after immobilization.
      The optimum pH of the immobilized enzyme was changed to acidic range. The optimum
      reaction temperature of immobilized enzyme was shifted slightly to 70-80 degrees
      C. Both of Km values and Vmax and thermal stability of immobilized enzyme were
      found to be higher than that of free one. Among the tested metals CaCl2 exerted a
      stimulating effect on the activity of alpha-amylase.

PMID- 19093445
TI  - Investigations on the flora of hornworts (Anthocerotopsida) and liverworts
      (Marchantiopsida) of Bafa Lake Natural Park (C11).
AB  - This study covers investigations on the hornworts and liverworts of Bafa Lake
      Natural Park, included in the C11th grid square. A total of 1 species belonging
      to a family of the class Anthocerotopsida and 26 species belonging to 15 families
      of the class Marchantiopsida of the division Bryophyta were collected and their
      habitat characteristics and taxonomical features were recorded. In addition, very
      rare collected species, as Targionia lorbeeriana, Mannia androgyna, Oxymitra
      incrassata, Riccia gougetiana, Petalophyllum ralfsii and Gonylanthus ericetarum,
      exist in this study.

PMID- 19093446
TI  - In vitro plant regeneration through anther culture of some Iranian local rice
      (Oryza sativa L.) cultivars.
AB  - In this study, effect of different genotypes, different callus induction and
      regeneration media were investigated using seven Iranian local rice. Anthers were
      cultured on N6, Fj and L8 media containing the same hormonal combination 3 mg L(
      1) NAA, 0.5 mg L(-1) Kn and 0.5 mg L(-1) 2, 4-D and incubated at 25 +/- 1 degree
      C in dark for callus induction. All varieties in L8 medium, five varieties in Fj
      medium and six varieties in N6 medium produced highest percentage of callus.
      Calli induced in different induction media were transferred to SK 11 and N 19
      medium and incubated at 25 +/- 1 degree C in light for plantlet regeneration.
      Among seven varieties upon transfer to SK 11 medium, highest percentage (40%) of
      green plants were produced in Hassani and in N 19 medium the highest percentage
      (15.78) of green plants and albino plants (21.05) were produced in Anbarbo. The
      finding in the present investigation showed that the successfully emberyogenesis
      and green plant regeneration in rice anther culture dependent on medium culture
      components and are affected by the genetic mack-up of the plants.

PMID- 19093447
TI  - PCR based on identification of vectors of zoonotic cutaneous leishmaniasis in
      Shahrood District, central of Iran.
AB  - A study was made in rural region of Shahrood city, Semnan province in the central
      of Iran during 2005 to investigate of vectors of zoonotic cutaneous
      leishmaniasis. Sticky traps and an aspirator were used for collecting of
      sandflies. Three species of Phlebotomus papatasi, P. caucasicus and Sergentomyia
      sintoni were collected and identified and the first species was dominant (53%).
      Nested PCR method were employed for identifying of isolated parasites of
      dissected female of sandflies. Among the dissected sand flies 3 out of 24 (12.5%)
      Phlebotomus papatasi and 2 out of 48 (4.2%) Phlebotomus caucasicus were found
      naturally infected with promastigotes. Species-specific amplification ofGiemsa
      staind promastigote slides revealed specific PCR production of Leishmania major
      DNA in the infected P. papatasi and P. caucasicus sand flies. Having high
      prevalence and infection rate provide enough evidence to incriminate of P.
      papatasi as the main and proven vector of cutaneous leishmaniasis to human in the
      region and the species of P. caucasicus play the second role for maintenance of
      disease between rodents.

PMID- 19093448
TI  - Chemodiversity of saponins and their taxonomic importance in Clematis genus
      (Ranunculaceae).
AB  - Distribution patterns of chemical compounds in plants have been used for
      biosystematic and phylogenetic studies. Saponin profile of twelve major taxa of
      Clematis genus, belonging to sections, Rectae, Clematis, Meclatis, Tubulosae and
      Viorna were analyzed by HPLC coupled with diode array detector and ESI-MS. The
      chemodiversity profile of saponins has unambiguously delimited the taxa of
      Clematis at subgenus, section and subsection level. The distribution of saponins
      in Clematis genus provides useful taxonomic markers and results are presented in
      phenograms. The compound Huzhangoside D was common and the most abundant in
      analyzed species of the genus. The morphological analysis was also conducted of
      the same taxa and presented as cluster tree. The distribution and chemotaxonomic
      importance of saponins profile within the genus is discussed.

PMID- 19093449
TI  - Toxicological studies of two compounds isolated from Loranthus globosus Roxb.
AB  - The sub-acute toxicities of two compounds 3,4-dimethoxycinnamyl alcohol (1) and
      3,4,5-trimethoxycinnamyl alcohol (2) isolated from the plant Loranthus globosus
      Roxb were studied on long Evan's rats. The studies included the gross general
      observation such as changes in body weight, haematological profiles [total count
      of Red Blood Cells (RBC) and White Blood Cells (WBC), differential count of WBC,
      platelet count and Haemoglobin (Hb)%], biochemical parameters of blood [Serum
      Glutamate Oxaloacetate Transaminase (SGOT), Serum Glutamate Pyruvate Transaminase
      (SGPT), Serum Alkaline Phosphatase (SALP), urea and creatinine) and
      histopathology of the liver, kidney, heart and lung of both control and
      experimental groups of rats. The changes in haematological and biochemical
      parameters were statistically not significant after the administration of
      compounds 1 and 2 in a dose of 300 microg/rat/day for consecutive 14 days. No
      abnormality was found in the histopathology of the liver, kidney, heart and lung
      in the experimental groups of rats following same dose when compared with control
      group. This preliminary study suggests that the isolated compounds may be used
      safely for clinical trial.

PMID- 19093450
TI  - Membrane transport of andrographolide in artificial membrane and rat small
      intestine.
AB  - In the present study, the possible drug interactions of andrographolide with co
      administering drugs such as acetaminophen, amoxycillin, aspirin, chlorpheniramine
      and norfloxacin to treat various infectious and inflammatory diseases that may be
      induced during absorption process were examined using artificial lipophilic
      membrane and everted rat intestine. The membrane transport of andrographolide
      across the artificial membrane was not affected by different pH of the medium
      (simulated gastric and intestinal fluids), different concentrations of
      andrographolide and co-administered drugs examined. In everted rat intestine,
      above co-administered drugs examined showed no significant effect on
      andrographolide membrane transport. The participation of efflux transporters such
      as P-glycoprotein and MRP2 in andrographolide transport was then examined, since
      andrographolide is a diterpene compound and some diterpene compounds are known as
      P-glycoprotein substrates. Cyclosporine, a P-glycoprotein/MRP2 inhibitor,
      significantly suppressed the efflux transport of andrographolide in distal region
      of intestine, whereas probenecid, an MRP inhibitor, showed no significant effect
      in both proximal and distal regions of intestine. These results suggest that P
      glycoprotein, but not MRP, is participated in the intestinal absorption of
      andrographolide and P-glycoprotein-mediated drug interactions occur depending on
      the co-administered drugs and its concentrations.

PMID- 19093451
TI  - Salt pretreatment enhance salt tolerance in Zea mays L. seedlings.
AB  - Recent molecular studies show that genetic factors of salt tolerance in
      halophytes exist in glycophytes too, but they are not active. If these plants
      expose to low level salt stress these factors may become active and cause plants
      acclimation to higher salt stresses. So because of the importance of these
      findings in this research the effect of salt pretreatment has been examined in
      Zea mays seedlings. To do the experiment four day old Zea mays seedlings (Var.
      single cross 704) pretreated with 50 mM NaCl for the period of 20 h. Then they
      were transferred to 200 and 300 mM NaCl for 48 h. At the end of treatment roots
      and shoots of seedlings were harvested separately. The changes of K+ -leakage,
      the amount of malondialdehyde, proline, soluble sugars and the Hill reaction rate
      were analyzed. The results indicated that the amount of K+ -leakage and
      malondialdehyde (MDA) have been increased because of salt-induced lipid
      peroxidation and membrane unstability. Soluble sugars and proline as
      osmoregulators has been increased in stress condition and in pretreated plants
      with NaCl were the highest. The rate of Hill reaction was reduced significantly
      in stressed plants. Therefore we concluded that salt stress causes serious
      physiological and biochemical damages in plants and salt pretreatment enhances
      tolerance mechanisms of plants and help them to tolerate salt stress and grow on
      salty environments.

PMID- 19093452
TI  - In vitro production of nitrite by low and high density sperm subpopulations of
      human, bull and ram.
AB  - The aim of present study was to characterize nitric oxide production via nitrite
      measurement as its stable metabolite in the different species of spermatozoa
      (human, bull and ram). Sperm samples were fractionated on the basis of density
      with the use of a three-layer Percoll gradient. Spermatozoa collected from the
      various percoll gradient interfaces (50/70 and 70/95%). Results showed that
      nitrite is produced by human, bull and ram spermatozoa, but in the same sample,
      there were no significant difference between high density (with higher percentage
      of motility) sperm subpopulation and low density (with lower percentage of
      motility) sperm subpopulation Therefore, it seems that spermatozoa with different
      motility in the one sperm population have the same production of NO in
      physiological conditionthat is different from pathological condition (e.g., in
      the subfertile men).

PMID- 19093453
TI  - Systemic dexamethasone and its effect on normal aerobic bacterial flora of cow.
AB  - This study was carried out on 17 Holestein, heifers, aged between 1 to 2 years
      for determining the normal aerobic bacterial flora and their changes after
      dexamethasone injection. Swab samples were taken from eye, ear, pharynx and
      vagina before and 5 days after twice dexamethasone treatment. Results indicated
      that Bacillus cereus and Corynebacterium pseudotuberculosis had higher frequency
      of isolations than the other bacterial flora in eye, ear and pharynx. Actinomyces
      pyogenes was isolated with considerable frequency from vagina. Klebsiella
      pneumoniae was also isolated from pharynx and its frequency was increased
      significantly after dexamethasone injection (p < 0.05).

PMID- 19093454
TI  - Biosystematics and plant proteomics: role of proteomics in plant phylogenetic
      analysis.
AB  - Since time immemorial, systematics has played significant role in every sphere of
      life. Biosystematics has evolved from folk taxonomy towards natural
      classification system and then culminated into homology based classification
      system. A good systematic approach is practical and predictive of phylogenetics
      of taxa incorporating different data. The morphological, chemical and molecular
      (genomics and proteomics) informations are used to explore the exact inter
      relationship among the organisms. Proteomics is an essential and inevitable
      aspect in plant biology which can help in deciphering the functions of the genes
      that are or will be sequenced. Proteomics has proved to be a good tool in
      characterisation of individual lines and genetic distances among the genera,
      species, subspecies, verities and populations describing their phylogenetic
      interrelationships. Two-dimensional electrophoresis (2-DE) is the major technique
      being applied for polypeptide characterization of each taxon for exploring
      phylogenetic or physiological relationships among organs, tissues or organisms.
      Moreover, proteomics can lead to unraveling the natural phenomena of plants
      development and their response to changing environment. These proteomic derived
      informations and their application in phylogenetic studies can be useful in agro
      biotechnology development for better yield and safe use of food and medicines.

PMID- 19093455
TI  - Acute effect of cadmium treatment on the kidney of rats: biochemical and
      ultrastructural studies.
AB  - The present study was designed to explore the nephrotoxic effect of
      intraperitoneal acute administration of CdCl2 (2.5 and 5 mg kg(-1) b.w.) in rats.
      A number of toxicological parameters in kidney were examined including
      malondialdehyde (MDA) and endogenous antioxidants, e.g., catalase (CAT),
      superoxide dismutase (SOD) and Glutathione Peroxidase (GPx). The parameters that
      indicate tissue damage such as serum urea and creatinine were also determined,
      along with the ultrastructural changes of kidneys. A correlation was found
      between the dose and the intensity of changes. The results demonstrated that
      cadmium administration increased renal MDA but decreased CAT, SOD and GPx
      activities. In parallel, serum creatinine and urea elevated. The glomerular
      ultrastructural changes observed in cadmium-treated rats included narrowing of
      the capillary lumen and swelling of the capillary endothelium with occasional
      loss of fenestrae. The mesangium was wide with increased mesangial matrix. Loss
      of homogenous appearance of basement membrane displaying ondulation and
      thickening in many areas and deterioration of the slit membrane structures formed
      by the podocytes were also noted. The effects of cadmium on proximal cell
      ultrastructure were focal loss of brush border, nuclear membrane damage,
      chromatin condensation, swelling of the mitochondria with regression of
      mitochondrial cristae, degranulation and disintegration of protein-synthesizing
      structures such as rough endoplasmic reticulum, increased number of lysosomes and
      ultimately cell death.

PMID- 19093456
TI  - Relationship between desert locust, Schistocerca gregaria (Forskal), infestation,
      environmental factors and control measures in Gazan and Makkah Regions, Saudi
      Arabia.
AB  - Desert Locust, Schistocerca gregaria (Forskal), is one of the most important
      insect pests in Saudi Arabia. Cultivated crops and the range lands are heavily
      affected by desert locust in some regions of Saudi Arabia. The objective of this
      study was to determine the extent of damage by the Desert Locust, Schistocerca
      gregaria (Forskal) to the range lands being used for grazing range animals in
      Gazan and Makkah regions of Saudi Arabia. However, it is very difficult to
      estimate accurately the total infested areas, which were sprayed with
      insecticides to control upsurges, outbreaks and plagues over the last five
      decades. Records of Desert Locust control are kept in the National Desert Locust
      Control and Research Center in Jeddah. Meteorological data was obtained from the
      Meteorology and Environmental Protection Administration (MEPA), Saudi Arabia. The
      data shows that the Desert Locust infestation was associated partially with the
      rainfall intensity in Gazan and Makkah regions. There was found a good
      relationship between Desert Locust infestation (Solitary phase), temperature and
      the relative humidity. The locust infestation was heavy during 1986-88, 1992-95
      and 1997-98 and about 1.8 million ha were treated with insecticides. Out of the
      total breeding/infested area, 43% was treated in winter months (October-February)
      and the remaining 57% was treated in spring season (March-June). The infested
      area was sprayed with Marshall, Carbosulfan (20%), Malathion (96%, Clorpyrifos;
      (48%) Fipronil (12.5%), Sumithion (100%) and Decis (12.5%). The study showed an
      excellent potential to determine the active locust infestation period in relation
      to the environmental factors for its effective control with insecticide sprays to
      minimize crop damage. The study highlighted the needs for further investigations
      in other locust infested areas with different environmental factors for planning
      future desert locust control programs.

PMID- 19093457
TI  - Chemical analysis of some Salvia species native to West Azarbaijan (Iran).
AB  - Present survey was performed on nine species of Salvia (Lamiaceae) growing wild
      in different regions of West Azarbaijan in Iran (S. limbata, S. vertisillata, S.
      macrochlamys, S. nemorosa, S. ceratophylla, S. candidissima, S. syriaca, S.
      multicaulis, S. sclarea). In this research, three of the most important
      biochemical characters such as total protein content, total oil content and fatty
      acids combination in seeds of these species were considered. Analysis of species
      average comparison variance conducted with ANOVA and Duncan's test (p < 0.05)
      revealed that there is a significant difference about protein content, oil
      content and fatty acid composition among species.

PMID- 19093458
TI  - Abundance and seasonal variations of zooplankton in the arid zone mangroves of
      Gulf of Kachchh-Gujarat, westcoast of India.
AB  - The zooplankton was assessed quantitatively and qualitatively in regard to their
      abundance in creek waters at three sites along the western mangrove of Kachchh,
      west coast of India, for a period of two years (1999-2000). Totally 69 forms of
      zooplankton were recorded currently from 3 stations. Of these, the copepods
      formed the dominant group. The population density in all the three sites varied
      from 30,000 to 210,000 organisms m(-3). Surface water temperature varied from 17
      to 37 degrees C. Salinity varied from 34.0 to 44.0% per hundred and the pH ranged
      between 7.0 and 8.9. Variation in dissolved oxygen content was from 3.42 to 5.85
      mg L(-1). These semi arid zone mangrove creek area having high densities were
      recorded during winter season.

PMID- 19093459
TI  - Wheat yield dynamics: a structural econometric analysis.
AB  - In this study we initially have tried to explore the wheat situation in Turkey,
      which has a small-open economy and in the member countries of European Union
      (EU). We have observed that increasing the wheat yield is fundamental to obtain
      comparative advantage among countries by depressing domestic prices. Also the
      changing structure of supporting schemes in Turkey makes it necessary to increase
      its wheat yield level. For this purpose, we have used available data to determine
      the dynamics of wheat yield by Ordinary Least Square Regression methods. In order
      to find out whether there is a linear relationship among these series we have
      checked each series whether they are integrated at the same order or not.
      Consequently, we have pointed out that fertilizer usage and precipitation level
      are substantial inputs for producing high wheat yield. Furthermore, in respect
      for our model, fertilizer usage affects wheat yield more than precipitation
      level.

PMID- 19093460
TI  - Cloning of active human manganese superoxide dismutase and its oxidative
      protection in Escherichia coli.
AB  - Superoxide radical (O2*-) is a toxic byproduct of oxidative metabolism that
      extensively damages cellular macromolecules and organelles. Superoxide dismutase
      (SOD) catalyzes the conversion of superoxide radical to hydrogen peroxide (H2O2)
      and molecular oxygen (O2) thus providing a biological defense against oxygen
      toxicity. The structural gene of human manganese superoxide dismutase (hMnSOD)
      was successfully cloned into the pET46Ek/LIC by using a Ligation Independent
      Cloning (LIC) technique. The recombinant human MnSOD was expressed in E. coli
      strain BL21(DE3)pLysS and purified to homogeneity by Ni2+ -NTA. Supplementation
      of Mn2+ in the bacterial growth media was proven to be crucial for production of
      enzymatically active hMnSOD. The recombinant enzyme revealed a specific activity
      up to 2,857 U mg(-1) as measured by inhibition of photoreduction of nitroblue
      tetrazolium (NBT). The molecular weight of each subunit was estimated to be 22
      kDa by SDS-PAGE. More interestingly, E. coli expressing hMnSOD provides
      resistance against oxidative stress induced by the herbicide paraquat up to 1.2
      mM. These findings gain insights into the biochemical characterization and
      significant roles of oxidative-protection of the hMnSOD in biological systems.

PMID- 19093461
TI  - Behavioural responses of Tribolium castaneum (Herbst) to volatiles identified
      from dry cocoa beans.
AB  - New hybrid types of cocoa beans are attractive to insects in storage, however
      some of the insects feed little, if at all, on these beans compared to those of
      the traditional type (mixed genotypes). Based on a sniffing test using GCMS,
      differences in flavour volatiles in these types of beans have been determined and
      from these, six major volatiles of cocoa beans were selected for olfactometric
      analysis using a Pettersson olfactometer to determine which of them contributed
      to the attraction of Tribolium castaneum (Herbst) to the cocoa beans. The
      behaviour of Tribolium was affected by dose of 2-phenyl ethanol, acetophenone, 3
      methyl butyraldehyde, ethyl butyrate, ethyl 3-hydroxybutyrate and butyl 2
      methacrylate. Compared to beans of the new hybrid varieties, beans of the
      traditional type cocoa contained less 3-methylbutyraldehyde but more ethyl
      butyrate and acetophenone. In future breeding programmes, reducing the amount of
      acetophenone and ethyl butyrate but increasing the amount of 3
      methylbutyraldehyde in cocoa beans may deter Tribolium from feeding on beans in
      storage.

PMID- 19093462
TI  - Comparison between different protocols of synchronization and their efficiency on
      pregnancy rate of dairy cattle.
AB  - In order to determine different protocols of synchronization and their efficiency
      on pregnancy rate after fixed-timed AI (TAI), 120 dairy Holstein cows (n=120)
      were assigned randomly to six groups: (1) two injections of Prostaglandin
      F(2alpha) (PG(f2alpha)) with 12 days apart as a control group, (2) two injections
      of Gonadotropin Releasing hormone (GnRH) with 9 days apart and an injection of
      PG(f2alpha) at day 7, (3) injection of GnRH and PG(f2alpha) with 7 days apart,
      then single injection of Estradiol Benzoate (EB) after 48 h, 4) injection of
      progesterone (P4) in conjugation with EB then after 7 days PG(f2alpha) injection
      and after 48 h an injection of GnRH were done, 5) as group 4 but EB was used
      instead of GnRH, 6)injections of PG(f2alpha) and EB conjugated with Human Chronic
      Gonadotrophin (hCG) with 12 h apart. Animals in group 1 (control), groups 2-5 and
      group 6 were inseminated after 72, 20 and 36 h, respectively. Serum P4
      concentration of group 4 (4.43 +/- 1.50 ng mL(-1)) was higher than control group
      (2.34 +/- 1.36 ng mL(-1)) at day 5 after insemination (p < 0.05); P4
      concentrations of groups 3 and 4 have significant differences with control group
      (2.69 +/- 2.64 and 2.56 +/- 1.40 versus 0.81 +/- 0.41 ng mL(-1), respectively, p
      < 0.05) at a day after second injection and groups 4 and 5 were in higher level
      of P4 concentration than control group at insemination time (3.14 +/- 1.9 and
      2.89 +/- 1.8 versus 0.45 +/- 0.19 ng mL(-1) respectively, p < 0.05). Pregnancy
      rate were 0, 50, 45, 10, 30 and 45% for group 1 (control) through 6,
      respectively.

PMID- 19093463
TI  - Induction of somatic embryogenesis in saffron using thidiazuron (TDZ).
AB  - In vitro propagation of saffron either through somatic embryogenesis or
      cormogenesis is considered to be an efficient alternative method for large-scale
      propagation of pathogen-free corms. In order to develop an efficient protocol for
      in vitro propagation of saffron, a factorial experiment was carried out based on
      completely randomized design to investigate the effects of various concentrations
      of TDZ (0, 0.1, 0.25 and 0.5 mg L(-1)) on somatic embryogenesis induction from 5
      different types of corm explants (terminal or axillary buds, upper or lower parts
      of the corm tissue and terminal buds from pre-treated corms at 4 degrees C for 2
      weeks). The results revealed that TDZ concentrations affected the induction of
      somatic embryogenesis significantly while different types of corm explants showed
      no significant effect on this process. Among TDZ concentrations used, 0.5 mg L(
      1) was the most effective treatment for embryogenesis induction. Embryogenic
      calli (globular stage) proliferated well when subcultured into MS medium
      supplemented with 0.25 mg L(-1) TDZ before transferring to hormone-free MS medium
      containing 6% sucrose for maturation (scutellar or horn-shape stage). Matured
      embryos were transferred to half strength MS medium without growth regulators for
      further development, from which microcorms were produced at the basal part after
      3 months.

PMID- 19093464
TI  - Factors affecting hydrogen production from cassava wastewater by a co-culture of
      anaerobic sludge and Rhodospirillum rubrum.
AB  - Series of batch experiments were used to investigate the effects of environmental
      factors, i.e., total nitrogen and total phosphorus concentrations, initial pH,
      illumination pattern and stirring conditions on hydrogen production from cassava
      wastewater by a co-culture of anaerobic sludge and Rhodospirillum rubrum. The
      maximum of the hydrogen yield of 150.46 and 340.19 mL g-COD(-1) was obtained at
      the total nitrogen and total phosphorus concentrations of 0.2 and 0.04 M,
      respectively. An effect of initial pH was investigated at COD:N:P ratio of
      100:10:1. Results indicated that an optimum initial pH for hydrogen production
      was pH 7 with a high hydrogen yield of 158.78 mL g-COD(-1) was obtained. No
      significantly different (p < 0.05) in the effect of illumination pattern (24 h of
      light and 12 h dark/light cycle) on hydrogen production were observed under
      continuous-illumination and periodic-illumination with hydrogen yield of 131.84
      and 126.92 mL g-COD(-1), respectively. Therefore, a periodic-illumination was
      applicable in hydrogen fermentation due to its cost-effective. Hydrogen
      fermentation with a stirring at 100 rpm provided more effective hydrogen
      production (164.83 mL g-COD(-1)) than static-fermentation (93.93 mL g-COD(-1)).
      The major soluble products from hydrogen fermentation were acetic and butyric
      acids, in the ranges of 28.33-48.30 and 35.23-66.07%, respectively, confirming an
      ability of a co-culture to produce hydrogen from cassava wastewater.

PMID- 19093465
TI  - A flow cytometric opsonophagocytic assay for measurement of functional antibodies
      elicited after immunization with outer membrane vesicle of Neisseria meningitidis
      serogroup B.
AB  - Opsonophagocytosis mediated by antibody and complement is the major defense
      mechanism for clearing Neisseria meningitidis from the host. Therefore, a newly
      developed phagocytosis assay based on flow cytometry (flow assay) was using sera
      obtained from rabbit postvaccination with outer membrane vesicle of N.
      meningitidis serogroup B, was done in order to evaluation of the potential
      efficacy of (experimental) meningococcal vaccines. The Outer Membrane Vesicles
      (OMVs) and control were injected intramuscularly into groups of five rabbit with
      boosters on 14, 28 and 42 days after the primary immunization. The serum on 0,
      14, 28, 42 and 56 days were collected and stored at -20 degrees C for next
      analysis. Phagocytic function of and intracellular oxidative burst generation by
      rabbit polymorphonuclear (PMN), against N. meningitidis serogroup B, was measured
      with flow cytometer, using dihydrorhodamine-123 as probes, respectively. We use a
      Coulter Epics XL-profile (USA) with an argon laser operating at 488 nm. The
      results of quantitative flow cytometric analysis of rabbit PMN function in
      hyperimmun sera with OMVs revealed a highly significant increase in
      opsonophagocytic responses against serogroup B meningococci after 56 day in
      comparison with the control group (p < 0.05). Present results indicated that OMVs
      could be as a candidate for vaccine toward serogroup B meningococci and a new
      standard flow cytometric method to measure the opsonophagocytosis activity by
      rabbit PMNs was shown by this study.

PMID- 19093466
TI  - Effect of phosphate solubilizing microorganisms on quantitative and qualitative
      characteristics of maize (Zea mays L.) under water deficit stress.
AB  - The effect of seed inoculation by phosphate solubilizing microorganisms on
      growth, yield and nutrient uptake of maize (Zea mays L. SC. 704) was studied in a
      field experiment. Positive effect on plant growth, nutrient uptake, grain yield
      and yield components in maize plants was recorded in the treatment receiving
      mixed inoculum of Glomus intraradices (AM) and Pseudomonas fluorescens (Pf). Co
      inoculation treatment significantly increased grain yield, yield components,
      harvest index, grain N and P, soil available P, root colonization percentage and
      crop WUE under water deficit stress. In some of investigated characteristics
      under well-watered conditions, chemical fertilizer treatment was higher than
      double inoculated treatments, but this difference was not significant. Seed
      inoculation only with AM positively affected the measured parameters as amount as
      co-inoculated treatments. According to the results showed in contrast to the
      inoculated treatments with AM+Pf and AM, the application of alone Pf caused a
      comparatively poor response. Therefore, this microorganism needs to a complement
      for its activity in soil. All of measured parameters in inoculated treatments
      were higher than uninoculated treatments under water deficit stress conditions.
      Furthermore, the investigated characteristics of co-inoculated plants under
      severe water deficit stress conditions were significantly lower than co
      inoculated plants under well-watered and moderate-stressed conditions. Therefore
      it could be stated, these microorganisms need more time to fix and establishing
      themselves in soil. The present finding showed that phosphate-solubilizing
      microorganisms can interact positively in promoting plant growth as well as P
      uptake of maize plants, leading to plant tolerance improving under water deficit
      stress conditions.

PMID- 19093467
TI  - The interplay between socio-demographic variables, nutritional and immune status
      of HIV-positive/AIDS patients.
AB  - This study examined the association between socio-demographic factors
      (educational level and employment status) and the nutritional and immune status
      of 35 HIV-positive/AIDS patients at baseline. Assessment of selected macro-and
      micronutrient dietary intake was done using a validated food frequency
      questionnaire. Evaluation of anthropometric profiles (body mass index, waist-hip
      ratio and percentage of body fat) was also evaluated. A questionnaire was applied
      to obtain information on the educational level and employment status of the
      patients. The CD4+ T-cell counts and viral loads of the same patients were
      determined using the flow cytometry and Polymerase Chain Reaction (PCR) method
      respectively. An association between educational level and dietary intake was
      significant (p < 0.05) for total dietary fibre, selenium and vitamin C. There was
      no significant (p > 0.05) association between the two socio-demographic variables
      (education and employment) and anthropometric profiles. The association between
      education, employment and CD4+ T-cell count was not significant (p > 0.05). The
      viral load showed a significant (p < 0.05) association with employment status but
      not correlated with education. The sample size or certain inherent biological and
      social factors probably affected the outcomes of the interplay between the two
      selected socio-demographic factors and the nutritional and immune status. It is
      suggested that the results of this study should be interpreted with caution.
      Further studies with larger sample sizes are recommended.

PMID- 19093468
TI  - A preliminary study on genotypic differences in transcript abundance of drought
      responsive genes in sugar beet.
AB  - In this study, four sugar beet genotypes of differing responses to drought were
      selected from a field experiment conducted under well-watered and water-limited
      conditions in 2004. In addition, two candidate genes: 2-cysteine peroxiredoxin (2
      cys prx) and Nucleoside Diphosphate Kinase (NDPK), thought to be associated with
      drought tolerance, were chosen from a previous proteomics study in sugar beet. An
      expression analysis of the two drought-regulated genes using semi-quantitative
      reverse transcription Polymerase Chain Reaction (RT-PCR) indicated that there
      were genotypic differences in the transcript abundance of the candidate genes
      with the differences in the expression level of 2-cys prx being likely associated
      with the drought responses of the genotypes in a two-year field study. However,
      the expression analysis of the genes has to be investigated at different stages
      of the stress period on more genotypes.

PMID- 19093469
TI  - Incidence of crown rot disease of wheat caused by Fusarium pseudograminearum as a
      new soil born fungal species in north west Iran.
AB  - Root rot and crown rot is one of the main important fungal diseases on wheat in
      North West Iran. The disease was studied during 1999-2004 growing seasons in four
      provinces including Qazvin, Zanjan, East Azarbyjan and Ardabil. Different wheat
      fields in the areas studied were visited and samples of the plants showing
      symptoms like chlorosis, withering, whiting of spikes, growth reduction and white
      heads were collected and transferred to the laboratory. Samples were surface
      sterilized with sodium hypochlorite and then cultured on common media (PDA) and
      specific media (PPA and CLA). Totally 155 fungal isolates belonging to five
      genera were identified and the pathogen most frequently isolated was Fusarium
      pseudograminearum (formerly known as F. graminearum Group 1). This species
      normally causes crown rot resulting in severe damage in several locations under
      dry spring conditions. The disease caused losses from 18-45.5% in the fields
      where the season and crop rotation allowed the disease to build up. Prolonged
      moisture stresses coupled with relatively high soil temperature in the fall
      enhanced early disease development on the roots and sub crown internodes.
      Environmental conditions and genetic susceptibility of cultivars were the two
      main factors affecting diseases incidence.

PMID- 19093470
TI  - Productivity, blood metabolites and carcass characteristics of fattening Zandi
      lambs fed sodium bentonite supplemented total mixed rations.
AB  - Thirty male Zandy lambs (25 +/- 0.50 kg BW, 10 lambs in each group) were randomly
      allocated in three (control, 2% bentonite and 4% bentonite) treatment groups.
      Lambs were fed Total Mixed Rations (TMRs) containing 75% Concentrate Mixture (CM)
      and 25% forage. Sodium bentonite was mixed with the CM part of TMRs before being
      mixed with the forage. The fattening period lasted 84 days and data were
      collected on the performance, blood metabolites and carcass characteristics of
      lambs. Results showed that sheep fed bentonite added diets had relatively higher
      feed intake than the control group which ended to slightly higher weight change
      with a fairly appropriate feed conversion ratio in bentonite fed animals.
      Compared to the control group, a reasonably lower glucose and urea concentration
      and a higher total protein content was observed in the blood of sheep fed
      bentonite supplemented diets. The use of bentonite in diets did not affect the
      blood cholesterol contents of sheep. Slaughter weights, carcass dressing out
      percentages and carcass cuts were a bit higher in sheep of bentonite fed groups
      compared to those in control group. Sheep fed bentonite added diets produced
      carcasses with lower subcutaneous fat thicknesses and lower fat-tail percentages.
      Furthermore, feed cost was estimated to be lower for sheep in 2% bentonite group
      than that in other two groups. In conclusion, the use of two-percent sodium
      bentonite is suggested for diets of fattening lambs in Iranian feed markets.

PMID- 19093471
TI  - The effect of administration of different levels of GnRH on the day 0, 5 and 12
      post-insemination on progesterone concentration in dairy heifers.
AB  - This study was carried out to evaluate the effects of different levels of GnRH in
      different days of reproductive cycle on progesterone concentration in dairy
      heifers. Two hundred heifers were divided into ten experimental treatment:
      control group with no injection (1) administration of 2.5 mL Gonadorelin (a GnRH
      analogue) in day of insemination (2) administration of 5 mL GnRH in day of
      insemination (3) administration of 10 mL GnRH in day of AI insemination (4)
      administration of 2.5 mL GnRH in day 5 post-insemination (5) administration of 5
      mL GnRH in day5 post-insemination (6) administration of 10 mL GnRH in day5 post
      insemination (7) administration of 2.5 mL GnRH in day 12 post-insemination (8)
      administration of 5 mL GnRH in day 12 post-insemination (9) administration of 10
      mL GnRH in day 12 post-insemination. Blood samples were collected in days 0, 5,
      12 and 19 post insemination (AI = Day 0) for analysis of serum P4 concentration.
      There was no significant difference among experimental groups on day of
      insemination. Evaluation of P4 concentration on day 19 illustrated differences in
      progesterone concentration between groups on day 19 post-insemination. P4
      concentration of serum in the day 19 post-insemination significantly increased in
      groups either by 5 or 10 mL injection of GnRH whether in day 5 or 12 post
      insemination versus control group (9.24 +/- 2.2, 8.6 +/- 1.96, 9.43 +/- 2.15 and
      9.42 +/- 2.14 versus 5.5 +/- 0.8, respectively; p < 0.05). GnRH administration in
      the day 5 and 12 post-AI significantly increased progesterone concentration that
      may decline early embryonic death and improve pregnancy rate.

PMID- 19093472
TI  - Effect of exogenous indole-3-acetic acid and naphthalene acetic acid on
      regeneration of damask rose cuttings in three growing media.
AB  - An experiment was conducted to evaluate the performance of various levels of
      indole-3-acetic acid (IAA) and naphthalene acetic acid (NAA) treatments i.e., 0,
      25, 50, 75, 100 mg L(-1) on the regeneration of damask rose (Rosa damascena
      Mill.) cuttings in different growing media at the research farm of Arid Zone
      Research Institute D.I. Khan during 2004. The data revealed significant effect of
      different levels of growth regulators and growing media on the rose establishment
      parameters viz., plant height, plant spread, number of primary shoots, secondary
      shoots and survival percentage. Maximum plant height (134.2 cm), plant spread
      (46.3 cm), primary shoots (6.3), secondary shoots (25) and survival percentage
      (94.72%) were recorded when the rose cuttings were applied with NAA at the rate
      of 50 mg L(-1). Among the plant growth regulators, Naphthalene Acetic Acid (NAA)
      was found to be superior to indole-3-acetic acid (IAA) for its stronger effect
      regarding all parameters. The optimum level of Naphthalene Acetic Acid (NAA) was
      found in the range of 50 and 75 mg L(-1), while no such conclusion could be drawn
      for indole-3-acetic acid (IAA) as all growth parameters were linearly increased
      up to the highest concentrations of IAA i.e., 100 mg L(-1). Regarding growing
      media, the leaf mould appeared the best in terms of its positive effect on
      establishment of rose cuttings by giving the maximum plant height (125.1 cm),
      plant spread (37 cm), primary shoots (5.2), secondary shoots (19.48) and survival
      percentage (85.67%), followed by soil + leaf mould, while soil media was least
      effective.

PMID- 19093473
TI  - Recurrent selection for maydis leaf blight resistance and grain yield improvement
      in maize.
AB  - Leaf blight of maize (Zea mays L.), caused by Bipolaris maydis (Nisik. and
      Miyake), is one of the major factors limiting maize production in the plain areas
      of Pakistan, particularly in the North West Frontier Province (NWFP). The
      objectives of this study were to estimate selection differential, expected and
      observed response to selection and heritability for maydis leaf blight resistance
      and grain yield and to determine progress from selection in a maize population.
      Two cycles of S, recurrent selection were conducted in broad based maize
      population, Sarhad White (SW). One hundred S, lines were compared with their
      respective original population (C0) as a check. The experimental material was
      evaluated under artificial epiphytotics during 2003 and 2004, at NWFP
      Agricultural University, Peshawar. Selection differentials, expected responses
      and heritability estimates were determined from the replicated S1 lines
      performance of the first cycle. The observed progress was estimated from the
      replicated S1 lines of the second cycle that were generated after recombination
      of selected S1 lines of the first cycle. Highly significant variations between
      the cycles were observed for MLB and grain yield. Moderate and high heritability
      estimates, desirable selection differentials and close correspondence of expected
      and observed response were manifested for MLB and grain yield. The positive
      percent deviation of inoculated from uninoculated trials in both cycles (C1 = 71%
      and C2 = 41%) for leaf blight indicated successful development of blight disease
      after artificial inoculation, while the negative percent deviation of inoculated
      form uninoculated trials (C1 = -21 and C2 = -6%) for grain yield indicated the
      impact of blight disease on grain yield. Blight disease was significantly reduced
      from 2.9 to 2.3, whereas, grain yield was significantly increased from 2041 kg
      ha(-1) cycle(-1) to 2527 kg ha(-1) cycle(-1) or 19% cycle(-1). This yield
      improvement in SW was probably the result of concomitant reduction in the blight
      disease severity by -26%. These findings suggested that S1 recurrent selection
      was quite effective in improving disease resistance and grain yield.
      Nevertheless, some additional cycles of selection may be required to further
      improving grain yield and resistance level to maydis leaf blight in SW maize
      population.

PMID- 19093474
TI  - Juvenile rheumatoid arthritis in children with Ebstein Barr virus infection.
AB  - Juvenile Rheumatoid Arthritis (JRA) is a disease of unknown etiology. A total of
      50 patients with JRA who were hospitalized in the Pediatrics Rheumatology Ward of
      Imam Khomeini Hospital in Tehran during the years 2001-2002, were assessed
      serologically (IgM and IgG specific viral capsid antigens) for EBV infection and
      their response to therapy was studied. Minimum age of the patients was at least 6
      months and mean age was 60.96 plus/minus 43.46 months. EBV infection was seen in
      44 (88%) patients 24 of whom were girls and 20 boys. Ninety two percent of girls
      and 83% boys were infected with the virus. Ebstein barr virus (EBV) infection was
      seen in 33 cases, 6 cases, 4 cases and 1 case in the polyarticular,
      pauciarticular, systemic and spondylitis group, respectively. Fifty four percent
      of EBV-positive patients with JRA did not respond to the classic therapy. EBV
      virus is involved in the pathogenesis of JRA and patients with EBV are in greater
      risk of developing JRA.

PMID- 19093475
TI  - The influence of size, sex and season on the feeding regime of Synodontis
      membranaceus (Osteichthyes: Mochokidae) in Jebba Lake, Nigeria.
AB  - The influence of size, sex and season on the feeding regime of S. membranaceus
      were examined over a period of 24 months in Jebba Lake, Nigeria using frequency
      of occurrence, numerical, gravimetric and index of Relative Importance (RI)
      methods. Dietary composition and feeding intensity were sex dependent. RI
      established that there was a progression from a detritivorous diet in fish below
      20 cm Standard Length (SL), through a transitional planktivorous phase (20-27 cm,
      SL), to a predominantly molluscivorous/insectivorous diet in fish above 27 cm SL;
      thus indicating a switch from a relatively passive filter-feeding habit when
      young to an active predatory habit at adult stage. Food preference also varied
      with season hence intraspecific competitions were low. Abundant food and ability
      to evolve trophic strategies that ensure optimum foraging in spite of seasonal
      changes enable S. membranaceus to maintain its overwhelming prominence and wide
      distribution in Jebba Lake.

PMID- 19093476
TI  - The effects of coadministration palmitic acid and oleic acid (omega 9) on spatial
      learning and motor activity in adult male rat.
AB  - In this study, the effects of oleic acid (10%) and palmitic acid (10%) on spatial
      learning and motor activity have been investigated. So, adult male Wister rats
      divided into four groups (n=10). Control group was fed with ordinary diet. other
      groups were fed with a diet containing oleic acid (10%) for 4 weeks or palmitic
      acid (10%) for 1 week. Also, coadministration group was fed with a diet
      containing oleic acid (10%) for 4 weeks plus palmitic acid (10%) for 1 week. In
      next step, rats were trained for spatial learning task by using T-maze at
      subsequently 9 days. Moreover, rats were tested for motor activity task by using
      Rota rod based on standard method. The results showed that the spatial learning
      and motor activity were significantly (p < 0.01, p < 0.001) increased in rats fed
      with oleic acid (10%) for 4 weeks. Also Spatial learning and motor activity were
      significantly (p < 0.001, p < 0.001) increased due to the diet containing
      palmitic acid 10% for 1 week. Also the Spatial learning and motor activity were
      significantly (p < 0.01, p < 0.001) increased in coadministration group diet
      containing oleic acid (10%) for 4 weeks and palmitic acid (10%) for 1 week but
      statistical test between three diet groups were not significant. A consensus has
      emerged from recent research that it is important the balance of the different
      type of fats. Because the type of fatty acids in the diet and ratio of these
      fatty acids determines the type of fatty acids that is available to the
      composition of cell membranes spatially in nerves system.

PMID- 19093477
TI  - Effects of neem leaf dust and a commercial formulation of a neem compound on the
      longevity, fecundity and ovarian development of the melon fly, Bactrocera
      cucurbitae (Coquillett) and the oriental fruit fly, Bactrocera dorsalis (Hendel)
      (Diptera: Tephritidae).
AB  - Neem leaf dust and a commercial formulation of neem were tested on adult
      Bactrocera cucurbitae (Coquillett) and Bactrocera dorsalis (Hendel) to determine
      their effects on the longevity, fecundity and ovarian development. Different
      combinations of neem leaf dust and a commercial formulation of a neem compound
      incorporated with sugar solution and adult rearing diets were tested. The
      Laboratory tests showed that ingestion of neem can significantly reduced the
      longevity and fertility of both the fly species. Significantly fewer pupae were
      collected from adults fed on laboratory rearing diet and nimbicidine as water
      source. Effect of neem treatment on the pupation and subsequent adult emergence
      of late-instar larvae was negligible. Microscopic observation indicated that the
      decreased fecundity was due to the block of ovarian development. Experimental
      results confirmed that neem can be effectively used as a safe alternative
      insecticide for the control of Bactrocera species.

PMID- 19093478
TI  - Copper-induce change in antioxidative system in maize (Zea mays L.).
AB  - Maize seedlings treated with various concentrations (25-100 microM) of copper for
      15 days. A progressive decrease of root length and biomass with increasing Cu in
      nutrient solution was observed. The roots accumulated significantly higher
      amounts of Cu than the above ground parts. Accumulation of copper resulted in
      more active lipid peroxidation in both roots and shoots, which was attributed to
      copper-induced additional oxidative stress. Activities of APX (ascorbate
      peroxidase), GPX (guaiacol peroxidase), GR (glutathione reductase) and
      CAT(catalase) were higher in both roots and shoots in response to copper
      accumulation. Changes in lipid peroxidation and antioxidant enzyme activities
      suggest that oxidative damage may be involved in copper toxicity.

PMID- 19093479
TI  - Efficiency of Timber Jack 450C with different loading volumes in different
      slopes.
AB  - Primary transportation is an upper time, expensive and hard labour. The most
      skidding are with using of rubber wheel of Timber jack 450C in Iran country that
      has devoted 60% of utilization expenses. In order to, investigate of slope and
      loading volume effects on time of loaded traveling had used time study for
      Timberjack 450C. In one of strip roads in parcel eleven of district two of Langa
      management plan forest (Kelardasht region in North of Iran) determined 5 and 3
      different slopes classes and volumes classes, respectively. Then, time study was
      performed in slope classes with different loading volume in downward skidding.
      The first, collection of data have noted in special form and then have converted
      to uniform unit of m sec(-1). Descriptive statistics for each data set were
      calculated using the SPSS software. With presupposition that loading volume and
      slope are effective on the obtained time, these parameters have analyzed. ANOVA
      and Tukey test were used for loading volume factor. For investigation slope
      factor had used of Mann Whitney non-parametric test in order to comparison of
      loaded traveling speed in different slopes. Results of present research had
      showed that influence of loading volume on the loaded traveling time is
      insignificant, but loaded traveling speed in different slope classes is
      significant (in slopes >30%) as, speed of skidder machine is decreased with
      increase of slope variable.

PMID- 19093480
TI  - Antimotility effect of hydroalcoholic extract of yarrow (Achillea millefolium) on
      the guinea-pig ileum.
AB  - The use of medicinal herbs among the general population gives rise to the
      possibility of therapeutic or toxic effects in patients that use these plants.
      The effects of Achillea millefolium hydroalcoholic extract on the contractile
      responses of the isolated guinea-pig ileum were investigated. The effect of the
      Achillea millefolium extracts at five concentrations ranging form 0.05 to 5 mg
      mL(-1) was tested. The terminal ileum was removed. Segments were fixed in an
      organ bath containing in Tyrode solution. Contraction changes in the tissues were
      monitored using force displacement transducer amplifier connected to physiograph.
      Each segment served as its own control. Achillea millefolium inhibited the
      contractile response in a dose-dependent manner. The 50% effective concentration
      values (EC50) were calculated, which was 1.5 mg mL(-1). Regression analysis had
      shown that with increasing in extract concentration the effect of extract was
      increased. The coefficient of extract dose was 0.031 mg. Present results
      demonstrate that extract prepared from the plant of Achillea millefolium
      inhibited electrical induced contractions of the guinea-pig ileum when tested in
      vitro. This effect is dose dependent and reversible.

PMID- 19093481
TI  - Quantitative and qualitative determination of dimethyl phthalate and N, N-diethyl
      m-toluamide in repellents commercial formulations by high performance thin layer
      chromatography.
AB  - In this study HPTLC was used for simultaneous quantitative and qualitative
      determination of N, N-diethyl meta toluamide (DEET) and dimethyl phthalate (DMP),
      which are the main elements and active ingredients in current chemical
      repellents. Some defined amounts of commercial form of 3 repellents included
      trench pomade, stick insect repellent (SIR), which is containing 33% of DEET and
      DMP60 (dimethyl phthalate 60%) dissolved in ethyl acetate solvent, separately.
      The method employed TLC aluminum plate precoated with silica gel plates (SiO4)
      60F245 as the stationary phase. The solvent system consisted of benzene-diethyl
      etherhexane (5:3:2, v/v/v) as mobile phase. The multiple level method used for
      spotting. Densitometric analysis of repellents was carried out using TLC scanner
      3 and CATS4 software in the absorption/reflection mode at 230 nm. According to
      the results, the type and amount of active ingredients in DMP60 lotion was 61.8 g
      (SE = +/-1.6) per 100 cc and in SIR, 31.3 g (SE = +/-0.8) diethyl meta toluamide
      per 100 g of repellents raw materials. Also the active ingredients in trench
      pomade were determined as a combination of DMP and DEET by rates of 5.5 g (SE =
      +/-0.2) and 25 g (SE = +/-l) per 100 g repellents commercial formulations,
      respectively. In this study, the value of Rf for DMP and DEET was calculated 0.71
      +/- 0.2 and 0.32 +/- 0.2, respectively. HPTLC is a suitable method to
      quantitatively and quantitatively determine repellents which have DMP and DEET
      active ingredients. Since most of commercial chemical repellents have this active
      ingredient, adjusting and setting HPTLC up can be important.

PMID- 19093482
TI  - Documenting and comparing plant species diversity by using numerical and
      parametric methods in Khaje Kalat, NE Iran.
AB  - The aim was to examine and document several aspects of numerical diversity such
      as species richness, species diversity and evenness and to compare diversity in
      different slope aspects of the area by using numerical and parametric methods.
      About 193 quadrats of 4 m2 were located according to the nature of vegetation.
      Species composition and their abundance were recorded in a two-year period (2005
      to 2006). The result of field investigation was collecting and identifying of the
      total 225 plant species belonging to 154 genera and 37 families. The abundance
      data were subjected to analyses by specific diversity packages to characterize
      and obtain numerical indices (Shannon, Simpson, Brillouin, McIntosh, etc.,) and
      parametric families of species diversity. Numerical indices were calculated and
      documented for monitoring purposes. The results of diversity in main slope
      aspects (N, S, E, W) showed higher species richness and species diversity indices
      in the north aspect than in the others but it was not true with evenness indices.
      About 30 species such as Acanthophyllum glandulosum, Acroptilon repens, Alcea
      tiliacea, Bromus sericeous, Astragalus turbinatus, Centaurea balsamita etc., were
      detected exclusively in the north aspect. This can be important in reducing the
      evenness. Diversity comparing by using rank-abundance plot as well as diversity
      ordering of Hill, Renyi and Patil and Taillie confirmed high species diversity in
      the north yet the result of ANOVA showed no significant differences in the four
      aspects. The result of diversity based on the models revealed that the whole
      area, the south and the west aspects follow lognormal distribution, north aspect
      follows logarithmic whereas the east follows both lognormal and logarithmic
      distribution. In other word, a shift from being lognormal to logarithmic model
      was observed in the east aspect.

PMID- 19093483
TI  - Resistance of Aedes aegypti (Diptera: Culicidae) in 2006 to pyrethroid
      insecticides in Indonesia and its association with oxidase and esterase levels.
AB  - Three strains of Aedes aegypti collected in 2006 from three major cities in
      Indonesia, i.e., Bandung, Palembang and Surabaya, were tested to determine their
      resistance status to pyrethroid (permethrin and deltamethrin) and also the
      resistance mechanisms regarding three detoxifying enzymes, i.e., oxidase,
      esterase A and esterase B. The resistance level was expressed as Resistance Ratio
      (RR) compared to the susceptible VCRU strain. Results of this study showed that
      Ae. aegypti in Indonesia has developed tolerance to permethrin and deltamethrin,
      except in the Bandung strain, which was resistant to permethrin and deltametherin
      with RR90 79.3 and 23.7, respectively. The study also suggested that detoxifying
      enzymes (oxidase, esterase A and esterase B) apparently were involved in the
      development of resistance in Bandung strain as indicated by the high level of
      activity of those enzymes in Bandung strain compared to other more susceptible
      strains. Although there is a possibility that other mechanisms, such as a target
      site resistance mechanism, in Bandung strain were also involved.

PMID- 19093484
TI  - Evaluation of antibacterial activity of selected Iranian essential oils against
      Staphylococcus aureus and Escherichia coli in nutrient broth medium.
AB  - The antibacterial effect of different concentrations (0.01 to 15%) of thyme
      (Thymus vulgaris), peppermint (Mentha piperita L.) caraway seed (Carum carvi),
      fennel (Foeniculum vulgar), tarragon (Artmesia dracunculus) and pennyroyal
      (Mentha pullegium) essential oils on the Staphylococcus aureus and Escherichia
      coli was studied in nutrient broth medium. The MIC values of peppermint, fennel,
      thyme, pennyroyal and caraway essential oils against Escherichia coli were 0.5 +/
      0.03, 1 +/- 0.03, 0.3 +/- 0.01, 0.7 +/- 0.03 and 0.6 +/- 0.02% and in contrast,
      for Staphylococcus aureus were 0.4 +/- 0.01, 2 +/- 0.13, 0.1 +/- 0.01, 0.5 +/-
      0.02 and 0.5 +/- 0.02%, respectively. The MBC values of peppermint, fennel,
      thyme, pennyroyal and caraway essential oils for Escherichia coli were 0.7 +/-
      0.02, 2 +/- 0.05, 0.5 +/- 0.02, 1 +/- 0.02 and 0.8 +/- 0.02 and for
      Staphylococcus aureus were 0.5 +/- 0.02, 4 +/- 0.26, 0.3 +/- 0.02, 0.7 +/- 0.02
      and 0.6 +/- 0.01, respectively. Statistical evaluation of the results indicated
      that the essential oils of thyme (Thymus vulgaris) showed the broadest spectrum
      of action (p < 0.05). Essential oils of peppermint (Mentha piperita), caraway
      seed (Carum carvi), pennyroyal (Menthae pullegium) and fennel (Foeniculum vulgar)
      had moderate effect against tested microorganisms and in contrast, tarragon
      essential oil were less effective against tested microorganisms. In conclusion,
      essential oils of edible plants could be a potential source for inhibitory
      substances for some foodborne pathogens. Natural substances that extracted from
      plants have applications in controlling pathogens in foods.

PMID- 19093485
TI  - Floristic study of Mirabad region.
AB  - The study area (Mirabad) is located between 36 degrees, 55' to 37 degrees north
      latitude and 45 degrees, 05' to 55 degrees, 44' east longitude in west Azerbaijan
      province. In this study, Flora of this region was determined by using available
      references. We encountered 192 species that belongs to 126 genera and 41
      families. The largest family of region is Asteraceae with 31 sp. and the largest
      Genera is Astragalus with 7 sp. The main life forms are: Hemicryptophyte with
      30.2% and Therophyte with 28.1%. The most extended chorotype with 62.5% is
      related to: Irano_Turanian.

PMID- 19093486
TI  - Selection for osmoregulation gene to improve grain yield of wheat genotypes under
      osmotic stresses.
AB  - For identifying osmoreguulation (or) differences in bread wheat genotypes, three
      experiments by using of randomized complete blocks design with five replications
      were carried out separately on 6 genotypes (Tabasi, Alvand, Shahi, Sabalan,
      Sardary and Roshan) under normal, drought and salinity stresses. At earring
      stage, in order to studying osmotic stress on pollen grains, treatments of 30%
      PEG (control) and 50% PEG with 10 mM KCl (osmotic stress) were applied. All
      pollen grains ofgenotypes were been swollen at control treatment, but under
      osmotic stress except of Roshan pollen grain (due to accumulation of K+ ion) was
      been shrinkage. Orthogonal analysis of variance showed significant differences
      for traits of grain yield and its components, soluble sugars, Na+, K+
      accumulations. Under stress Roshan genotype had high accumulation of soluble
      sugars and K+. Increasing of grain yield due to or gene at Roshan than other
      genotypes under drought and salinity stresses were, respectively 18.14 and
      38.80%. So, under drought and salinity stresses, identification of or allele and
      selection based on it in wheat breeding programs are strongly recommended.

PMID- 19093487
TI  - Effect of different hormonal combinations on regeneration of callus of Gomphrena
      globosa L.
AB  - The main aim of this study was to observe the effect of different hormonal
      combinations on regeneration of callus of Gomphrena globosa L. For this purpose
      callus was obtained from seeds G. globosa inoculated on MS medium supplemented
      with 4 mg L(-1) 2, 4-D and 10% coconut milk. After callus formation callus was
      inoculated on Murashige and Skoog's medium supplemented with different
      combinations of BAP, NAA and GA3 to observe different responses such as
      regeneration, callus friability, callus proliferation and pigmentation. In BAP
      and NAA root regeneration was observed at 1.5 mg L(-1) BAP+1 mg L(-1) NAA whereas
      rest of the combinations showed callus proliferation. In BAP and GA3, root
      regeneration was observed in most of the combinations and some combinations also
      showed shoot induction. Shoot regeneration was observed on 0.5 mg L(-1) BAP + 7
      mg L(-1) GA3 and 1 mg L(-1) BAP + 0.2 mg L(-1) GA3. The effect of all these
      combinations on auxin, acid phosphatase and soluble protein content was also
      observed.

PMID- 19093488
TI  - Evaluation of genetic diversity in Aegilops tauschii accessions using
      morphological and AFLP markers.
AB  - Thirty two accessions of Aegilops tauschii were used to assess its genetic
      diversity by morphological and AFLP data and to evaluate relationship between
      morphological and AFLP markers. Thirty AFLP primer combinations led to the
      amplification of fragments ranging from 50 to 500 bp of which, 97 were
      polymorphic across the 32 accessions. Although both AFLP and morphological data
      classified accessions in two groups, one possessing subsp. tauschii accessions
      and the other contained all accessions of subsp. strangulata with some accessions
      from the subsp. tauschii. This may be explained by intermediate and hybrid forms
      between these two subspecies. Comparison of UPGMA dendrograms of morphological
      and AFLP markers using the cophenetic correlation indicated a non significant
      correlation (r = 0.37). Nevertheless, AFLP and selected morphological characters
      appear as useful and complementary techniques for evaluation of genetic diversity
      in subspecies of A. tauschii.

PMID- 19093489
TI  - Efficacy of aniseed extract as immune stimulant and growth promoter in broiler
      chicks.
AB  - Present research was undertaken to investigate the effect of different level of
      6% concentrated (w/v) aniseed extract in broiler chicks at NWFP Agricultural
      University Peshawar Pakistan. One hundred and sixty, day old broiler chicks were
      randomly assigned to four treatments, as A, B, C, receiving 20, 30 and 40 mL of
      6% (w/v) concentrated aniseed infusion and D was kept as control group. Each
      treatment was replicated four times with ten chicks per replicate. Chicks were
      reared in cages in an open sided house. Vaccination was done against ND and IBD.
      Data were recorded for growth performance, immunity and economics. The data were
      subjected to statistical analysis, using Completely Randomized Design and MSTATC
      programme. Mean feed and water intake was nonsignificant (p > 0.05). Mean weight
      gain, FCR and dressing percentage was found better (p < 0.05) in group C. Mean
      weight of giblet, intestine, breast, fat and thigh was not altered (p > 0.05) in
      all groups. Mean antibody titer against IBD was higher (p < 0.05) in group C and
      antibody titer against ND and IB was not altered. Mean percent mortality was
      found higher (p < 0.05) in group D. Mean feed cost including the cost of aniseed
      infusion was not influenced (p > 0.05), while the gross return was found better
      (p < 0.05) in group B and C than other groups. Findings of the research study
      indicated that group C, receiving aniseed infusion at the rate of 40 ml L(-1) of
      water shown better growth performance, immunity and gross return. Detail research
      work is needed to examine the effect of aniseed in ration and its different form
      of extracts on poultry production under different environmental conditions.

PMID- 19093490
TI  - Determination of digestible and metabolizable energy of fishmeal and soybean meal
      in rainbow trout with two different sizes (Oncorhynchus mykiss).
AB  - The present research carried out to measure digestible (DE) and Metabolizable
      Energy (ME) for fishmeal and soybean meal in rainbow trout with two different
      sizes (120 and 220 g mean body weights). DE and ME are evaluation systems for
      feedstuffs and also, necessary for diet formulation. The fishes were maintained
      in metabolic chamber with single ingredient assay of feeding and chromic oxide
      (Cr2O3) was used as an external marker using total fecal collection method. Gross
      energy and chromic oxide values measured in feces, fishmeal and soybean meal. The
      results indicated that DE offishmeal was 3700 and 3591 kcal kg(-1) in 120 and 220
      g body weight rainbow trout, respectively. Soybean meal had 3004 and 2889 kcal
      kg(-1) respectively. Calculated ME from DE were 3204 and 3110 kcal kg(-1) for
      fishmeal and 2601 and 2502 kcal kg(-1) for soybean meal in 120 and 220 g rainbow
      trout, respectively. The results showed that rainbow trout can utilize fishmeal
      more efficiently than soybean meal.

PMID- 19093491
TI  - The effect of stem pruning and nitrogen levels of on some physico-chemical
      characteristics of pumpkin seed (Cucurbita pepo L.).
AB  - To investigate the effects of stem pruning (No heading, head pruning of stem
      after formation of 10 and 14 nodes) and nitrogen levels (0, 50, 100 and 200 kg
      ha(-1)) on physical and chemical characteristic of pumpkin seed a Factorial
      experiment based on randomized complete block design with three replication was
      carried out in Gorgan at 2003 and repeated in 2004 years. Results showed that the
      stem pruning has significant effect on traits such as seed oil, linoleic acid and
      oleic acid content. Nitrogen levels also have significant effect on seed
      dimension, seed oil, linoleic acid and oleic acid content. The largest amount of
      oil and linoleic acid content was obtained by stem pruning after forming 14 node
      and 100 kg ha(-1) nitrogen in separately, but the interaction of treatments were
      not significant difference for all of traits.

PMID- 19093492
TI  - Selected heavy metals in blood of male Nigerian smokers.
AB  - Lead, cadmium and zinc levels were determined in the blood of 47 all male smokers
      (age range, 19-56 years). The subjects were classified into 4 subgroups based on
      the number of years of smoking, namely: 1-5, 6-10, 11-15 years, >16 years. Thirty
      all male non-smokers serves as the control. The weight, height and body mass
      indexes of all subjects were noted in addition to other information obtained
      through structured questionnaire. Those that were likely to be exposed to any of
      these metals either occupationally or through other life style habits were
      excluded from the study. The mean values of blood lead (BPb), blood cadmium (BCd)
      and blood zinc (BZn) in male smokers (n=47) were 43.26 +/- 4.28, 98.21 +/- 6.39
      and 104.84 +/- 3.66 microg dL(-1), respectively while the corresponding mean
      values for these parameters in the non smokers (n = 30) were 32.44 +/- 3.02,
      76.51 +/- 4.59 and 90.38 +/- 2.55 microg dL(-1), respectively. The smokers have
      statistically significant higher BPb, BCd and BZn than the non-smokers (p <
      0.001, p < 0.001 and p < 0.001, respectively). The results appear to confirm the
      presence of these metals as component of cigarette and agree with similar
      findings from literature. Consequently, it is probable that high level of these
      metals in blood of smokers is from tobacco smoking. Additionally it appears that
      the number of years of smoking has nothing to do with the level of these metals
      in smokers' blood.

PMID- 19093493
TI  - Measuring tree height and preparation volume table using an innovative method.
AB  - Zarbin (Cupressus sempervirence var. horizontalis) with its unique
      characteristics is one of the worthiest species which can be found in the central
      area of Alborz in the North of Iran. Especially in the Roodbar-manjil area,
      Chaloos-Hassanabad valley as well as it extends from Zarringol area to Gorgan.
      Although the distribution areas of this species have been protected, these
      forests have been invaded by the villagers who use this useful wood. For this
      reason in the Roodbar area, trees with DBH>30 cm are extremely rare. To recognize
      and to be aware of the stand quantity, the current research tries to calculate
      the species volume table in Roodbar area, to be the basis for any calculation of
      the volume of stand in the region. For this purpose, trees have been sampled
      using the line sampling method. After estimating the form factor, Tarif table
      have been prepared. In this study, a new method for measuring tree height is
      presented, in which, instead of measuring slope distance from observer to tree
      (which is difficult in young conifers because of existence branches in lower
      height) distance between the eye level of observer to tree butt is measured.
      Which doing of it is easier, time of field work is decreased and accuracy of
      measurement and calculation is increased.

PMID- 19093494
TI  - Leptin gene polymorphism in Iranian native Golpayegani and Taleshi cows.
AB  - The objective of the present investigation was to study genetic variations in the
      exon II of leptin gene in Iranian Golpayegani and Taleshi cows. Blood samples
      were collected from 76 Golpayegani and 64 Taleshi cows randomly selected from
      Delijan city (Esfahan province) and Talesh city (Guilan province) in Iran,
      respectively. Genomic DNA was extracted from 100 micro litters of blood using
      guanidium thiocyanate-silica gel method. A 94 bp fragment from exon II of the
      bovine leptin gene was amplified using the polymerase chain reaction. Digestion
      of PCR products with Bsp13I restriction enzyme differentiated C and T alleles.
      The T allele frequencies were 0.29 and 0.45 in Golpayegani and Taleshi breeds,
      respectively. The frequencies of the genotypes CC, CT and TT were 0.42, 0.58 and
      0 in Golpayegani and 0.36, 0.36 and 0.27 in Taleshi cows. The average
      heterozygosities were 0.41 and 0.50 in Golpayegani and Taleshi breeds,
      respectively. The chi2 test did not confirm the Hardy-Weinberg equilibrium in
      both populations.

PMID- 19093495
TI  - The interrelationship between nutrition and the immune system in HIV infection: a
      review.
AB  - Available scientific evidence has revealed that macronutrients and micronutrients
      are critical for fighting HIV-infection, because they are required by the immune
      system and major organs to attack infectious pathogens, HIV inclusive. It is
      believed that weight gain or maintenance might be achieved through good nutrition
      and has helped to reduce the consequences of wasting in people living with
      HIV/AIDS. Nutrition has helped to strengthen the immune system and reduce the
      severity and impact of opportunistic infections in people living with HIV/AIDS.
      It is known that an immune dysfunction as a result of HIV/AIDS leads to
      malnutrition and this in turn leads to further immune dysfunction. Various
      research studies have confirmed that nutrient deficiencies are associated with
      immune dysfunction and accelerated progression to AIDS. In this review, the
      interrelationship between nutrition and immune system in HIV infection is
      presented.

PMID- 19093496
TI  - The use of certified seeds of improved wheat varieties in farms and the
      contributions of certified seed usage to enterprise economies: the case of Ankara
      province in Turkey.
AB  - In this research, the use of certificated seeds of improved wheat varieties in
      farms of Ankara, which have an important share in wheat production of Turkey and
      the contributions of the certified seeds usage to enterprise economy have been
      evaluated by using data collected from farms via a questionnaire. The low level
      of use of certificated wheat seed in farms is associated with many factors, such
      as price of the seed (cost), yield gains and suitability of the varieties for the
      farming aims of producers. Average productivity is 49.5% and average net profit
      is 39.7% higher in the production of wheat with certificated seeds of improved
      varieties in farms in comparison to farming with traditional varieties. Average
      productivity in wheat production with uncertified seeds of improved varieties is
      24.9% and net profit per unit area is 24.3% higher than wheat production with
      traditional varieties. The net economic benefit of wheat production using
      certificated seeds of improved varieties and that of wheat farming with
      uncertified seeds has been estimated at $ 102.40 and $ 62.70 ha(-1),
      respectively. Some $ 6.4 benefit is generated in return for $ 1 of expense in
      wheat farming with certificated seeds of improved varieties instead of
      traditional varieties. In the absence of state subsidies for certificated seeds
      the use of uncertified seeds seems to be advantageous for producers. While the
      amount of subsidy per hectare will be a minimum of $ 101 for certificated seeds
      per hectare of planting area (as technological improvement), the support will be
      encouraging for usage of certified seeds. Many variables, such as farm size, use
      of certified seeds, topography of land, production system, education level and
      frequency of visiting the agriculture organizations of the producers influence
      the level of gross profit per unit area in wheat farming. Low level of use of
      certificated seed in farms decreases the economic benefit of new varieties which
      are developed as a result of long term research and development studies and with
      a large amount of expense and causes the return of expenses to take a long time,
      if ever.

PMID- 19093497
TI  - Effect of between and on row distance of first development, tillering, yield and
      yield components in wheat cultivars (Triticum sp.).
AB  - This study was carried out at the University of Ankara, Faculty of Agriculture,
      Haymana Research and Application Farm, Haymana County, Ankara, Turkey during
      1987/1990 with the aim of to determine the effect of between and on row distances
      (B(rd) and O(rd), respectively) on the first development, tillering, yield and
      yield components in wheat cultivars (Triticum sp.). Five wheat cultivars
      (Bezostaja-I, Gerek 79, Haymana 79; Triticum aestivum L., Cakmak 79 and Kunduru
      1149; Triticum durum Desf.) were used and experimental design was arranged in a
      Randomized Completely Block Design (RCBD) in split plots with four replications.
      The cultivars were allocated to the main plots at three different B(rd) (5, 10
      and 17.5 cm) and six various O(rd) (4.7, 2.2, 1.2 cm in commons and 3.8, 1.8, 1.0
      cm in durums) values. B(rd) and O(rd) distances were not affected from emergency
      date; the number of plant m(-2) was varied between 173-326; the number of
      tillering was m(-2) was determined between 12-86; the number of the first root
      was changed 3-4; the length of the adventitious root was happened between 89-116
      mm; the number of the adventitious root was varied between 2-3 mm; the length of
      the adventitious root was realized between 42-74 mm; the number of the downy
      brome (Bromus inermis Leyss.) was changed between 7-16; plant height was measured
      between 45-73 cm; spike length was recorded between 62-81 mm; the number of
      spikelet was determined between 16-23; the number of grain was found between 19
      30; grain weight per plant was calculated between 1-2 g plant(-1); 1000-kernel
      weight was varied between 18-44 g and grain yield per m2 was fixed between 119
      208 g m(-2). Increasing in the B(rd) and O(rd) were negatively effected the
      adventitious root development so to ensure a long and fertile spike, narrow B(rd)
      and O(rd) distances should be used. Spikelet and grain number, 1000-kernel weight
      and grain yield per m2 were increased by narrowing either between nor on row
      distances. In addition, all the B(rd) parameters were not significantly effected
      to seedling traits in commons but not in durums. B(rd) = 17.5 cm was found the
      most beneficial distance in durums. On the other hand, to avoid reducing of the
      yield components, between row distance should not be increase and in all
      circimcustances, that value always must be adjusted wide otherwise control of the
      weeds, diseases and pest could be a great problem during the cultivation.

PMID- 19093498
TI  - Effect of cowpea seeds contamination rate by the Cowpea aphid borne mosaic virus
      on epidemics development.
AB  - Cowpea aphid borne mosaic virus (CABMV) diseased seeds provide at seedling, virus
      infected plants which are the only source of primary inoculum. Secondary
      infections are bequeathed by aphids. The objective of this research is to study
      the development of the secondary infection in field. Therefore, eight cowpea
      varieties with different seed contamination rate (0, 0.05, 0.25, 0.5, 1, 5%) were
      used over consecutive four years. The infected plants were recorded every week
      from the tenth day after sowing and over seven weeks. In the same way, aphids'
      population were evaluated in plots 30 days after sowing. There was no difference
      for the incidence rate between the average of plots sown with virus free-seeds
      and those sown with infected seeds with a rate of 0, 5%. In any case, the disease
      progressed lowly leading to incidences less than 50% at the post-flowering period
      in spite of a relatively high initial contamination rate of seed. For this group
      of varieties, the low progression of the disease indicated a high level of
      resistance to the infection. The high levels of infection especially observed
      with the varieties with high level of virus transmission to seed, translated the
      need to reduce aphids' population density notably by the use of insecticides
      during cowpea growing cycle. The high number of aphids and inoculum availability
      in the neighbouring plots were undoubtedly at the source of this result. This
      situation laid out the problematic of the use of seeds then little or not
      contaminated by the virus.

PMID- 19093499
TI  - Some characteristics of soils on the man made mounds in the Harran Plain of
      Turkey.
AB  - Morphological, chemical and some mineralogical characteristics of five soils,
      were researched to understand the genesis of soils on the man made mounds in the
      Harran Plain, in the Southeast Anatolia Region of Turkey. Five soil profiles
      developed on the man made mounds in the arid region. Time and climate have
      affected soil formation. Also, parent material has influenced the chemistry of
      soils. The parent material of man made mounds were carried from around soils in
      the Harran Plain by men in years ago. The parent materials of around soils are
      calcareous parent materials and alluvium materials. Pedon 1 was described on the
      Konuklu man made mounds the northeast of the study area and Pedon 5 was described
      on the Kupluce man made mounds the southeast of the study area. According to the
      place of man made mounds were ordered from north to south as following: Pedon 1,
      Pedon 2, Pedon 3, Pedon 4 and Pedon 5. The old of Konuklu mounds is approximately
      5000-6000 years. The old of Sultantepe and Koruklu mounds are approximately 6000
      years. Pedon 4 which was described on the old Harran city remnants have the
      youngest soils of study area. The Harran mounds was made in 1258 A.I. by
      Mongolians. Mongolians destroyed the Harran City and made the Harran mounds. The
      most important pedogenic processes is carbonate leaching and accumulation in the
      pedon 5 on the Kupluce man made mounds. The CaCO3 content of Pedon 5 may be
      attributed to eolian addition from Syria. Total Al2O3 contents of soils higher
      than total Fe2O3 content. According to the degree of soil formation the profiles
      were ordered as following: Pedon 3 > Pedon 5 > Pedon 2 > Pedon 1 > Pedon 4. The
      results of total elements analysis were used to determine the beta leaching
      factor according to Jenny. The leaching factor were determined as < 1 in the
      Pedon 1 (0.99), Pedon 2 (0.97), Pedon 3 (0.74) and Pedon 5 (0.92). The leaching
      factor were determined as >1 in the Pedon 4(1.13).

PMID- 19093500
TI  - A morphological identification in fish of the genus Puntius Hamilton 1822
      (Cypriniformes: Cyprinidae) of some wetlands in Northeast Thailand.
AB  - This investigation was carried out at the Department of Fisheries, Khon Kaen
      University, Khon Kaen, Thailand in collaboration with the Department of
      Biosciences, University of Hertfordshire, Hatfield, United Kingdom. The work was
      carried out in the 2003 to 2006 to taxonomically identify fish of the genus
      Puntius Hamilton 1822 harvested from 15 wetlands in Northeast Thailand. Some
      considerable amounts of fish samples were collected and used for morphological
      characteristics identifications both measuring and counting. The fish samples
      were kept in a 10% formalin solution for two weeks and then transferred to a 75%
      ethanol alcohol for laboratory determinations. Thirty fish samples from each
      location were used. The results showed that there were 9 fish species of the
      genus Puntius Hamilton 1822 harvested from 15 locations (provinces). They
      include: Puntius altus, Puntius aurotaeniatus, Puntius binotatus, Puntius
      gonionotus, Puntius leiacanthus, Puntius orphoides, Puntius partipentazona,
      Puntius schwanenfeldi and Puntius wetmorei. The fish samples of the 9 species
      were morphologically identified where the information include 45 characteristics
      on morphological measurements and 18 characteristics for counting. However, with
      this work only 20 important characteristics are included. The obtained results
      were calculated through the computer programmes commencing from the use of an
      Excel programme for raw data inputs followed by Statistica (PCA values),
      Multivariate by SAS and then NTSYSpc2.10 for UPGMA dendrogram figure. The results
      showed that the 20 important characteristics did not provide any multivariate
      values of significant differences found among the 9 fish species. The values on
      Euclidean distances of the 9 species ranged from 0.31-0.61 where there were no
      significant differences found among the 9 fish species of the genus Puntius
      Hamilton 1822, thus the fish of the 9 species could not be shifted or split into
      to other genera apart from the genus Puntius Hamilton 1822.

PMID- 19093501
TI  - Effects of grazing on chemical soil properties and vegetation cover (case study:
      Kojour rangelands, Noushahr, Islamic Republic of Iran).
AB  - This research is conducted to study the effects of grazing on chemical soil
      properties and vegetation cover in three areas separated as the key, reference
      and critical areas. The study area is located at the river basin of Kojour in the
      Southwestern of Noushahr (in the North of IR-Iran). Sampling and collecting the
      soil and vegetation cover data from the site areas are accomplished in the first
      step of the research. The vegetation cover data was collected in 20 sample plots
      of 1 m2 in each area. The data was collected through a random- systematic method
      in the early grazing season. The soil data was collected out of two layers (0-10,
      10-30 cm), in two time intervals before and after grazing. Five samples were
      selected per layer. Some edaphical factors such as organic carbon, percentage of
      soil organic matters, total nitrogen, absorbable phosphorus and potassium, pH and
      EC were measured. The results revealed that there is an inverse relationship
      between the grazing intensity and amount of carbon, nitrogen, soil organic matter
      and EC. However, a direct relation exists between the grazing intensity and
      amount of soil potassium, phosphorus, pH and the ratio of carbon to nitrogen.
      Vegetation in class 1 and 2 which were cereals and forbs had greatest percentage
      in the reference area. Furthermore, the percentage forage cover increases with
      the grazing intensity. The more unpalatable vegetation of class 3 forms the
      prevailing coverage in the critical area. The conclusion of this study shows that
      overgrazing is considered as a threat for the nutritional elements of soil and
      vegetation cover.

PMID- 19093502
TI  - Host-parasite relationship of S. mansoni and B. glabrata.
AB  - Experiments were conducted to study the host-parasite compatibility of various
      isolates of Biomphalaria glabrata snail and Schistosoma mansoni parasite
      isolates. A series of experiments conducted on 12 S. mansoni isolates have shown
      a range of infectivity potential for B. glabrata snail and 9 isolates of B.
      glabrata were found differentially susceptible to infection with S. mansoni
      trematode parasite.

PMID- 19093503
TI  - Soil decontamination of 2,4,6- trinitrotoluene by alfalfa (Medicago sativa).
AB  - Present study investigate the toxicity effect of 2,4,6-trinitrotoluene (TNT) on a
      terrestrial plant, alfalfa (Medicago sativa) in artificial soils. In this study,
      TNT toxicity assessment was performed on spiked silica with this nitroaromatic
      compound by determination of the percent of emergence and shoots and roots
      biomasses at the concentration range of 3.2-10000 mg kg(-1) Dry Weight (DW). The
      emergence was reduced by 22-32% after 5 days of exposure at TNT concentrations up
      to 100 mg kg(-1) DW; shoot and root biomasses were reduced by 48-50 and 63-74%,
      respectively after 30 days exposure at TNT concentrations < or = 32 mg kg(-1) DW.
      Concentrations higher than 100 mg kg(-1) DW can not be tolerated at all.
      Concentrations of TNT and its metabolites in silica, root and shoot were measured
      by High-Performance Liquid Chromatography (HPLC). Analyses of TNT spiked soil
      extracts reveal hat during alfalfa cultivation for 30 days, TNT was partially
      transformed at the extent of 15-27%. This transformation decreased at higher TNT
      soil concentrations. TNT is taken up and metabolized by plants to its downstream
      derivatives.

PMID- 19093504
TI  - Ultrastructural alterations and occurrence of apoptosis in developing follicles
      exposed to low frequency electromagnetic field in rat ovary.
AB  - Humans are continuously exposed to harmful environmental factors, including
      Electromagnetic Fields (EMF) produced by home appliances, diagnostic tools and
      industrial instruments. The present study investigates morphologically the
      effects of EMF on ovarian follicles. Female Wistar rats were exposed to 3 mili
      Tesla EMF for 4 h day(-1) for 4 months, the ovaries from both experimental and
      control groups were processed for Transmission Electron Microscopy (TEM) and
      TUNEL reaction technique. TEM revealed that in the oocytes from experimental
      group the nuclei were shrunken and zona pellucida appeared narrower than those in
      the control group. The number of microvilli were decreased significantly and in
      their cytoplasm there were several lipid droplets and organels were dispersed.
      Signs of apoptosis such as condensed nuclei, chromatin margination and nuclear
      membrane dilatation were common in granulosa and corona radiata cells from the
      EMF-exposed rats than those from the control group. Primary morphological changes
      in the granulosa cells from this group were retraction of granulosa cells, loss
      of microvilli and condensation or loss of mitochondrial cristae. The
      morphological changes in oocytes seem to indicate the cytotoxic effect of EMF and
      the changes occurred in granulosa cells coincide with initiation of apoptosis in
      granulosa cells. Present results suggest that EMF exposure may interfere with
      normal process of folliculogenesis.

PMID- 19093505
TI  - Nitrogen contents of rice panicle and paddy by hyperspectral remote sensing.
AB  - The nitrogen content or crude protein content in rice grains is one of the
      important indices to evaluate the nutrition and taste quality of rice. Normal
      determination of their contents by chemical methods is highly expensive and time
      consuming. The hyperspectral reflectances of the canopy, flag leaf and panicle of
      5 rice varieties are measured by a ASD FieldSpec Pro FR in field under 3 nitrogen
      support levels in maturing process. The nitrogen contents of stems, leaves, flag
      leaves, panicles and rice paddy and their crude protein contents are determined.
      The correlation among them is analyzed. The panicles nitrogen contents (%) are
      very significantly correlate not only to that of stems, leaves and flag leaves
      and chlorophyll contents (mg g(-1)) of flag leaves at milking and maturing
      stages, but also to the spectral reflectance rho(lambda), the first derivative
      spectra D(lambda) and RVI of canopy, flag leaf and panicle itself. The nitrogen
      contents (%) of rice paddy are very significantly correlative to that of stems
      and leaves and the spectral reflectance rho(lambda), the first derivative spectra
      D(lambda) and RVI of canopy at some wave bands at booting, milking and maturing
      stages. For the squared multiple correlation coefficients (R2) of estimating the
      nitrogen contents of panicle and paddy by canopies spectra, we find R2 > 0.80 at
      milking stage, R2 > 0.75 at maturing stage, but for the estimation of panicle by
      the spectra of flag leaf and panicle itself, we have R2 > 0.65. It indicates that
      it can be feasible for estimating the contents of nitrogen and crude protein in
      rice grains by hyperspectral remote sensing. It provide basis for monitoring rice
      quality by remote sensing.

PMID- 19093506
TI  - The effect of yeast (Saccharomyces cerevisiae) on nutrient intake, digestibility
      and finishing performance of lambs fed a diet based on dried molasses sugar beet
      pulp.
AB  - This experiment was conducted to determine the effect of yeast (Saccharomyces
      cerevisiae, SC47) on finishing performance, digestibility, some blood metabolites
      and carcass characteristics of male lambs fed a diet based on dried Molasses
      Sugar Beet-Pulp (MSBP). Eighteen Sanjabi male lambs (20.95 +/- 2.7 kg initial
      body weight and 3 month of age) were used in a completely randomized design.
      Animals were assigned to one of the two dietary treatments (with or without
      yeast). Digestibility and nitrogen balance experiment was carried out using six
      mature rams on finishing diet with and without yeast. Serum metabolites were
      determined in samples taken from lambs at the end of finishing period. Dry matter
      digestibility of finishing diet was significantly increased by yeast addition.
      However, yeast did not have any significant effect on apparent digestibility of
      OM, NDF, CP and energy. Nitrogen retention was also not affected by yeast
      addition. Yeast resulted in a significant increase in the average daily gain, dry
      matter and organic matter intake. However, feed conversion ratio was not
      significantly affected by addition of yeast. The concentration of the serum
      metabolites including glucose, urea, cholesterol, sodium, potassium, calcium,
      phosphorous and cratinine were not affected significantly by yeast
      supplementation, but triglyceride concentrations increased significantly when
      yeast was fed. Addition of yeast to the diet did not have any significant effect
      on the carcass characteristics. Results of this study suggest that feeding
      saccharomyces cerevisiae with a diet based on MSBP can improve the performance of
      fattening lambs without any change in carcass characteristics or cuts.

PMID- 19093507
TI  - Mycoflora of maize harvested from Iran and imported maize.
AB  - The natural occurrence of fungal contamination was evaluated in stored maize in
      three different agro-ecological zones (Iran, Brazil and China). A total of 45
      samples were analyzed and 685 fungal isolates were identified. The most frequent
      isolated fungi from maize originated from Iran, Brazil and China were Fusarium
      sp. (17.3, 17.9 and 37.1%), Aspergillus sp. (9.3, 17.4 and 19.7%),Penicillium sp.
      (5.8, 15.2 and 17.6%), Rhizopus sp. (2.4, 3.2 and 3.5%), Mucor sp. (1.1, 1.6 and
      1.3%), Cladosporium sp. (1.6, 1.9 and 1.9%), Alternaria sp. (1.1, 1.6 and 1.3%),
      Geotrichum sp. (0, 0 and 0.3%), Acromonium sp. (0.5, 0.8 and 0%) and Absidia sp.
      (0, 0.8 and 0.5%), respectively. Significant difference was observed between the
      frequency of fungal isolates of Iranian maize and foreign products (p < 0.0005).
      Maize mycoflora profiles showed that Fusarium verticillioides and Aspergillus
      flavus prevailed in 30.7 and 13.3% of the samples from China, in 12 and 5.3% of
      the samples from Iran and 11.7 and 11.5% of the samples from Brazil,
      respectively. There were significant differences in the frequency of Fusarium
      verticillioides in Chinese maize with other countries products (p < 0.0005) and
      that of Aspergillus flavus in Iranian maize with other countries (p < 0.002). The
      results emphasize that farmers and consumers should be alerted to the danger of
      fungal contamination in maize.

PMID- 19093508
TI  - Heavy metal composition of some solid minerals in Nigeria and their health
      implications to the environment.
AB  - Heavy metals overload taken via ingestion, inhalation and dermal have been found
      to be detrimental to both the occupationally exposed group and member of the
      public. The body burden of these metals has been a source of concern in
      environmental safety regulatory programs. The risk factor becomes potentially
      high in an environment where regulatory safety criteria are either neglected or
      not available. The implication of indiscriminate or unregulated mining activities
      has been pointed out as a major risk to public health. In order to assess the
      potential toxicological and radiological health hazard posed to the environment
      due to mining activities in Nigeria, solid mineral ores (iron, tin and tantalite)
      from south-western and north-central (Kogi and Ekiti States) part of the country
      were analysed for their trace-metal contents. The analysis was performed using
      Energy Dispersive X-Ray Fluorescence (EDXRF) analyses spanning several months
      between 2005 and 2006. The samples were found to contain some major, minor and
      trace elements of varying concentrations. The elements reported here are K, Ca,
      Ti, V, Cr, Mn, Fe, Ni, Sr, Y, Zr, Nb, Sn, Ta, Re, Th, U, Sc, Cd, Bi, Ra and Zn.
      Toxic metal of serious environmental and public concern like Cadmium was
      detected. The possibility of altering heavy metal constituents of the natural
      ecosystem as a result of mining activities and the implications of such
      alterations has been enumerated. Possible pathway into the food chain as a result
      of mining activity has also been presented.

PMID- 19093509
TI  - Effect of nibbling and gorging dietary regimens on weight and lipid profile in
      rat.
AB  - To investigate the effects of nibbling and gorging dietary regimens on weight and
      lipid profiles in rat, thirty female Wistar rats, after 10 day acclimatization
      period, were weighed and randomly assigned into two equal groups. They were fed
      the same food for 60 days as eight meals at 2 h intervals starting from 6 pm
      (nibbling group) or as two meals at 9 pm and 6 am (gorging group). The serum
      lipid levels and weight of animals were determined before and after the
      intervention. The body weight in two groups increased significantly (p < 0.001)
      during the period of study but there was no significant (p > 0.05) difference
      between two groups before and after the intervention. Nibbling regimen caused a
      reduction in the serum Total Cholesterol (TC), triglyceride and LDL-C levels,
      whereas these parameters increased during gorging diet. However, none of these
      changes were significant. There was a significant decrease (p < 0.05) in TC and
      LDL-C levels in nibbling diet compared to gorging one. According to obtained
      results, nibbling regimen has better effect on lipid profile than gorging one in
      rat.

PMID- 19093510
TI  - Identification of salt tolerant rice cultivars via phenotypic and marker-assisted
      procedures.
AB  - Eleven genotypes, including the salt tolerant cultivar Pokkali as check, were
      used to evaluate salinity tolerance phenotypically and genotypically. Three
      selected SSR primers viz., RM7075, RM336 and RM253 were used to evaluate rice
      genotypes for salt tolerance. Two setups were maintained for this study viz., the
      seedling and reproductive stages. Phenotyping at the seedling stage was done in
      hydroponic system using salinized (EC 12 dS m(-1)) nutrient solution and at the
      reproductive stage using salinized tap water (EC 6 dS m(-1)). IRRI standard
      protocol was followed to evaluate salinity tolerance in rice. The genotypes
      having similar banding pattern with Pokkali were considered as tolerant.
      Phenotypically, three genotypes Pokkali, THDB and TNDB-100 and five genotypes RD
      2586, TNDB-100, Dhol Kochuri, PNR-519 and Pokkali were identified as salt
      tolerant at the seedling and reproductive stages, respectively. These genotypes
      were also identified as salt tolerant genotypically (with markers). Through
      phenotypic and genotypic study, five genotypes viz., Pokkali, Dhol Kochuri, RD
      2586, TNDB-100 and PNR-519 were identified as salt tolerant. Therefore, these
      microsatellite markers used in this study could be efficiently used for
      identification of salt tolerant rice varieties in marker-assisted breeding and
      quantitative trait loci analysis.

PMID- 19093511
TI  - Microsatellite variation in one breed of Iranian sheep with 12 markers.
AB  - Polymorphic loci, genetic parameters (Polymorphic Information Content,
      heterozygosity, Shannon Index, the number of actual alleles, the number of
      effective alleles) and genetic variation within Balouchi sheep population located
      in Abbasabad station of Mashad, was assessed using 12 microsatellite markers. The
      Polymerase Chain Reaction (PCR) reactions were successfully done with all primers
      except for OarHH62 and OarAE64, one locus (CSSM059) was monomorph, whereas the
      other 9 loci containing CSSM018, CSSM006, BMS1004, BMS2361, BMS744, BMS799,
      BMS1316, BMS2213 and TGLA122 were polymorph with 6, 6, 4, 4, 5, 4, 2, 3 and 3
      number of alleles, respectively. In this population, heterozygosity varied from
      0.5 to 0.72; among 9 polymorphic loci, BMS1316 and BMS2361 had the most and the
      least diversity, respectively. The study of Shannon Index and Polymorphic
      Information Content (PIC) indicate the least and the most values for BMS1316 and
      BMS2213 loci, respectively. The most number of actual alleles were belong to
      CSSM018 and CSSM006 loci with 6 alleles and the least was belong to BMS1316 locus
      with 2 alleles. BMS2361 locus had the most and BMS1316 locus had the least number
      of effective alleles. All loci were at Hardy-Weinberg equilibrium (p < 0.005). In
      this population, average heterozygosity was estimated as 0.54. In general, it can
      be concluded that Balouchi sheep population of Abbasabad station in Mashad (in
      Iran) has approximately high genetic diversity with respect to the studied
      microsatellites and microsatellite markers have approximately high polymorphism
      and therefore can be used for genetic studies.

PMID- 19093512
TI  - Seroepidemiologic study of hepatitis B virus, hepatitis C virus, human
      immunodeficiency virus and syphilis infections in Iranian blood donors.
AB  - To determine the frequency of hepatitis B, hepatitis C, Human Immunodeficiency
      Virus (HIV) and syphilis infections in Iranian blood donors. The prevalence of
      serological markers of hepatitis B, hepatitis C, HIV and syphilis infections were
      evaluated in 318029 consecutive volunteer blood donors attending to Tehran blood
      transfusion service from March 2005 to March 2006. Those positive for hepatitis B
      surface antigen, anti-HCV, anti-HIV1/2 and VDRL (venereal disease research
      laboratory) reactivity were analyzed with a second independent HBsAg enzyme
      immunoassay (EIA) and neutralization assay; an additional independent anti-HCV
      EIA and HCV-RIBA assay; second independent anti-HIV1/2 test, HIV western blot and
      fluorescent Treponemal Antibody Absorbed (FTA-ABS), respectively. In 318029
      participants, prevalence of positive HBsAg, HCV RNA, HIV western blot and FTA-ABS
      was 1684 (0.487%), 323 (0.093%), 11 (0.003%) and 19 (0.005%), respectively. In
      1014 subjects randomly selected from these 318029 participants, besides standard
      interview, physical exam and routine serologic tests; anthropometric and
      biochemical were studies. In this selected group frequency of HBsAg was 3 (0.29,
      95% CI: 0-0.64%); frequency of anti-HCV was 21 (2.07%), but it was (0.09%, 95%
      CI: 0-0.30%) by confirmatory HCV RNA test; frequency of HIV-Abl, 2 was 8 (0.78%),
      but it was 2 (0.19%, 95% CI: 0-0.48%) by confirmatory test; frequency of RPR was
      0 (0%, 95% CI: 0-0.30%). Despite excluding subjects with high-risk behaviors by
      standard interview and physical examination, still a few asymptomatic hepatitis
      B, hepatitis C, HIV-infected subjects existed among volunteer blood donors with
      demographic and biochemical findings similar to non-infected ones.

PMID- 19093513
TI  - Antifeedant and toxic activity of some plant extracts against larvae of cotton
      leafworm Spodoptera littoralis (Lepidoptera: Noctuidae).
AB  - The biological activity of crude petroleum ether extracts of Oshar (Calotropis
      procera); Harmal (Rhazya stricta) and Hargal (Solenostemma argel) were assessed
      using the 4th larval instar of cotton leafworm Spodoptera littoralis (Boisd.)
      (Lepidoptera: Noctuidae). All extracts exhibited a significant antifeedant
      activity at the LC50 levels. Harmal extract deterred feeding potential of insect
      larvae by 52.96% but decreased to 26.76 and 18.00% for Hargal and Oshar,
      respectively. In nutritional assays, all plant extracts affected Growth Rate (GR
      mg) where Harmal caused the highest rate of efficiency and followed by Oshar
      against 4th larval instar fed for two days on castor leaves treated with
      botanical extracts (LC50) and three days on un-treated leaves after that. Hargal
      didn't show a significant effect on growth rate compared with un-treated larvae.
      The differences between Consumption Index (CI mg) of larvae treated with Hramal
      and Hargal after five days of feeding in comparison with un-treated larvae were
      significant. Efficiency of Conversion of Ingested food (ECI%) to biomass reached
      31.81 +/- 1.49, 26.06 +/- 1.89 and 48.67 +/- 1.54 after five days of treatment by
      Oshar, Harmal and Hargal, respectively. These values were 49.61 +/- 1.72, 39.12
      +/- 0.54 and 53.20 +/- 0.96 for digested food utilization (ECD%) in larvae
      treated with the aforementioned extracts after five days, respectively. There was
      a remarkable inhibitory activity of plant extracts on the digestive carbohydrate
      enzymes, amylase and invertase in vitro. It was noticed that Harmal had a
      remarkable inhibitory action causing an average of 42.58% inhibition rate on
      amylase and 16.27% on invertase followed by Hargel and Oshar with inhibition
      rates of 33.27 and 19.58% against amylase, while these values averaged 11.19 and
      5.97% of inhibition in case of invertase, respectively.

PMID- 19093515
TI  - Influence of intestinal cestodes on the blood picture of the brown rats (Rattus
      norvegicus) of Hyderabad Sindh, Pakistan.
AB  - Present study was performed to determined the changes in the blood picture of the
      brown rats Rattus norvegicus naturally infected with intestinal cestodes. The
      results are based on the examination of 82 brown rats captured at random from
      Hyderabad city and its adjacent areas. Blood profiling of cestode (Hymenolepis
      diminuta and Hymenolepis nana) infected male and female rats showed significantly
      lower values of Total Erythrocyte Count (TEC), Haemoglobin (Hb) concentration,
      Haematocrit (Hct), Mean Corpuscular Haemoglobin (MCH) and Mean Corpuscular
      Haemoglobin Concentration (MCHC) as compared to their control (non-infected) rats
      of both sexes. The Mean Corpuscular Volume (MCV) value for infected male and
      female rats was found significantly higher than those of their control rats. A
      significantly higher Total Leukocyte Count (TLC) in male and female infected rats
      was noted as against the non-infected (control) rats of both sexes. The
      Differential Leukocyte Count (DLC) revealed significant increase in absolute
      number of each type of cell in cestode infected male and female rats. However,
      lymphocyte and basophil counts recorded from male infected rats were similar to
      the counts of their control rats. Conspicuous changes in the blood picture of
      cestode infected male and female rats indicate host-parasite interaction as well
      as the triggering of defense mechanism in the host against infection.

PMID- 19093514
TI  - Co-composting of palm oil mill sludge-sawdust.
AB  - Composting of Palm Oil Mill Sludge (POMS) with sawdust was conducted in natural
      aerated reactor. Composting using natural aerated reactor is cheap and simple.
      The goal of this study is to observe the potential of composting process and
      utilizing compost as media for growing Cymbopogun citratus, one of Malaysia
      herbal plant. The highest maximum temperature achieved is about 40 degrees C and
      to increase temperature bed, more biodegradable substrate needs to be added. The
      pH value decrease along the process with final pH compost is acidic (pH 5.7). The
      highest maximum organic losses are about 50% with final C/N ratio of the compost
      is about 19. Final compost also showed some fertilizing value but need to be
      adjusted to obtain an ideal substrate. Addition of about 70% sandy soil causes
      highest yield and excellent root development for C. citratus in potted media.
      Beside that, compost from POMS-sawdust also found to have fertilizer value and
      easy to handle. Composting of POMS with sawdust shows potential as an alternative
      treatment to dispose and recycle waste components.

PMID- 19093516
TI  - Progesterone receptor positive colorectal tumors have lower thymidine
      phosphorylase expression: an immunohistochemical study.
AB  - Present study aimed to find the clinicopathological significance of PgR and its
      association with TP expression in colorectal cancer. Immunohistochemical studies
      were performed on 83 colorectal adenocarcinoma patients using corresponding
      monoclonal antibodies of PgR and TP and LSAB detection kit. Mucin producing cells
      showed PgR expression and its expression was detected in 15.6% of normal and 59%
      of malignant tissues. Significant association were observed between PgR negative
      expression in malignant tissues and larger tumor size (p = 0.006), higher
      incidence of secondary organ metastasis (p = 0.014) and tumor pathological stage
      (p = 0.041). A close association was observed between PgR and lack of TP
      expression in malignant tissues that means out of 49 PgR (+) tumors, 43 cases
      (86%) were TP negative (p = 0.046). It seems that tumors with better prognosis
      were more likely to express PgR in their malignant tissues, which affects the
      expression of TP as one of the major therapeutic targets in CRC. Present study
      suggests progesterone therapy as a possible effective strategy to suppress
      colorectal cancers and as a novel anti-angiogenic therapy for tumor dormancy
      which needs complimentary studies for confirmation.

PMID- 19093517
TI  - Chlamydia trachomatis prevalence in Iranian women attending obstetrics and
      gynaecology clinics.
AB  - This study was designed to estimate the prevalence of Chlamydia infection in
      women attending Obstetrics and Gynaecology clinics in Tehran, during May 2003 to
      October 2003. Women attending Obstetrics and Gynaecology clinics aged 15-42 were
      recruited by Sequential Random Sampling. Those who had not passed urine in the
      last hour were eligible. Informed consent was obtained and a questionnaire
      completed after being interviewed by a midwife. First void urine was collected
      and after DNA extraction from urine specimen, PCR tests were performed; urine DNA
      samples were tested by strand displacement amplification (SDA) for Chlamydia
      confirmation. 12.6% (133/1052) tested positive for Chlamydia by PCR. Of these PCR
      positive samples, 86 were available for re-testing by SDA and 67 were positive
      giving a correlation between the tests of 78%. This gave an overall true
      prevalence of 6.4% which is however, underestimated. No statistical differences
      were seen between patient age groups, details of personal and reproductive
      history and combined PCR and SDA positivity for C. trachomatis. A 12.6%
      prevalence of Chlamydia trachomatis was found by PCR testing which is cost
      effective to screen and treat. Despite limitations in re-testing PCR-positive
      samples by SDA, a 78% correlation between tests confirms a high prevalence of C.
      trachomatis. Non-invasive screening of women was therefore a success in this
      group of patients. As this was the first time that more sensitive molecular
      methods were used for detection of C. trachomatis, prevalence in such a big
      sample size, the results are considerable. However, we suggest further such
      testing.

PMID- 19093518
TI  - Growth indices of winter wheat as affected by irrigation regimes under Iran
      conditions.
AB  - An experiment was conducted during 2004-2006 at the Agricultural Research
      Station, Islamic Azad University, Khorasgan Branch, Isfahan, Iran. The purpose of
      this study was to evaluate the effects of irrigation regimes on growth indices of
      three bread wheat (Triticum aestivum L.) genotypes. A split plot layout with a
      randomized complete block design with four replications was used. Irrigation
      treatments (irrigation after 70 (I1), 90 (I2) and 110 (I3) mm cumulative
      evaporation from class A evaporation pan) were considered as the main plot and
      three wheat genotypes (Mahdavy, Ghods and Roshan-Backcross) as subplots. The I1
      and I2 did not differ significantly for all growth indices, total dry matter and
      grain yield. Delay in irrigation from the I2 to I3 significantly reduced growth
      indices, total dry matter and grain yield. Trend of changes in Leaf Area Index
      (LAI), Total Dry Matter (TDM), Net Assimilation Rate (NAR) and Crop Growth Rate
      (CGR) were similar in the I1 and the I2. In all samplings, delay in irrigation
      from the I2 to I3 reduced all growth indices. The trend of changes in crop growth
      rate was more similar to leaf area index, than to net assimilation rate.
      Genotypes were not significantly different in respect to growth indices. The
      results indicate that irrigation after 90 mm cumulative evaporation from class A
      evaporation pan might be suitable for winter wheat production under conditions
      similar to this experiment where irrigation water during spring is not abundant.

PMID- 19093519
TI  - Effects of different concentrations of aflatoxin B on ram epididymal and
      ejaculatory sperm viability and motility in vitro.
AB  - The present study was carried to observe the effect of aflatoxin on ovine sperm
      in vitro. Ram epididymal and ejaculatory sperm cells were added into media
      containing different concentrations of aflatoxin B1. When ram epididymal sperm
      were put in different concentrations of aflatoxin, one-hour post incubation in
      control group, 81.25% of sperm cells were alive of which, 82.88% were motile.
      Significantly (p < 0.05) higher than medium with 31.25 ppb and higher
      concentration. The lowest motility (15.93%) was observed in 62.5 ppb aflatoxin.
      Sperm viability did not significantly changed after 2nd and 3rd h incubation but
      significantly decreased in 4th and 5th h post incubation. However, motility was
      not altered in the 2nd, 3rd, 4th and 5th h post incubation. In ejaculatory sperm,
      one hour post-incubation, in control group, 83.24% of sperm were alive of which
      93.98% were motile, significantly (p < 0.05) higher than motility in medium with
      7.81 ppb and higher concentrations of aflatoxin but not different with 1.96 ppb
      aflatoxin. In 62.5 ppb aflatoxin, the lowest motility was observed (18.9%). Sperm
      motility patterns for both epididymal and ejaculatory sperm cells were different
      after incubation in different concentrations of aflatoxin. The results of the
      present experiment showed that aflatoxin could decrease sperm motility obtained
      from ejaculation or epididymis.

PMID- 19093520
TI  - Practical approach for typing strains of Leishmania infantum by enzyme
      polymorphism: a cross sectional study in Northwest of Iran.
AB  - In present study, All samples collected from Kalybar and Ahar districts in
      Northwest of Iran from 12 patients (bone marrow aspirates), 26 dogs (spleenic and
      hepatic aspirates) and more than 100 sand flies between years 2004-2006. All
      patients were clinically diagnosed to have visceral leishmaniasis. Serological
      profiles of all sera samples from both human and dogs were in accordance with
      leishmaniasis (DAT). Isoenzyme profiles of these isolates were compared with
      those of reference using 12 enzyme systems. L. infuntum MON-1 is the only
      zymodeme present in all samples of dogs, sand flies and human. The enzymatic
      polymorphism is compared to that of neighboring countries (Azarbaijan, Iraq and
      Turkey etc.) and we concluded that the Visceral Leishmaniasis (VL) focus in
      northwest of Iran is evidently Mediterranean focus of zoonotic VL, which extends
      from Portugal and Morocco to Pakistan and the central Asian republics. Domestic
      doges act as the reservoir host, where Phlebotomus kandellakii and Perfiliewi
      ariasi are vectors.

PMID- 19093521
TI  - Investigation of plowing depth effect on some soil physical properties.
AB  - Tillage or plowing quality is usually evaluated by the soil bulk density and
      distribution of organic matter. Soil bulk density, which is the sign of
      compactness and porosity in turn, depends on type of implements, soil organic
      carbon, tillage method and plowing depth. Plowing depth causes a lot of pulling
      in tractors and in order to have deep plowings, heavy-duty tractors are needed.
      To determine the optimum depth of moldboard plow, the bulk density and soil
      organic carbon of cultivated soil were investigated in this research. The
      experiments were conducted, using a three-bottom plow with three plowing depths
      and four depth of soil, in a split plot design, which lasted for three years.
      Main plots, consisted of three plowing methods (shallow approximately 12 cm, semi
      deep approximately 22 cm and deep till age approximately 32 cm) and subplots,
      consisted of four soil depths (0-10, 10-20, 20-30 and 30-40 cm). The amounts of
      soil density, soil organic carbon, soil water infiltration and crop yields were
      measured. The results showed that, deep tillage had the greatest effects on soil
      densities, soil organic carbon, infiltration rates and crop yields. Mean value of
      soil bulk density was 1.65 g cm(-3) in shallow tillage which decreased by
      increasing the plowing depth to 1.53 and 1.151 g cm(-3) in semi-deep and deep
      tillage, respectively. However, soil bulk density associated with deep tillage
      was generally higher than that of semi-deep tillage but the differences between
      the semi-deep and deep tillage were not significant. The soil water infiltration
      increased from 1.234 cm h(-1), in shallow tillage to 1.405 cm h(-1) in deep
      tillage. Crop yield by the deep tillage was 6571 kg ha(-1), while the semi-deep
      tillage and shallow tillage yield were 6389 and 5717 kg ha(-1), respectively. By
      increasing the plowing depth, the soil organic carbon and crop yields improved
      but there were no significant differences between the semi-deep and deep tillage
      system.

PMID- 19093522
TI  - Evaluation of outer membrane proteins of Pseudomonas aeruginosa as a protective
      agent in mice model.
AB  - The crude Outer Membrane Protein (OMP) from a strain of P. aeruginosa isolated
      from burn patient was purified by two different methods. One procedure involved
      separation of Sodium Dodecyle Sulphate (SDS) and Triton X-100, where as the other
      involved using lysozyme enzyme. Both methods showed very similar polypeptide
      pattern and the major peptide band with molecular weight of 37 KD was common in
      both procedures. The protein estimation of OMP extracted by lysosyme was 3 mg mL(
      1) compared to 5.5 mg mL(-1) extracted by Triton-X100 method. The latter was
      chosen to examine for the immunogenicity study in a mice model. The efficacy of
      immunization with OMP and challenge with homologous strain in mice showed a very
      good protection compared to control mice injected with saline. The passive
      haemoagglutination test (PHA) in mice, injected with OMP showed increased level
      of antibody after the second injection and stayed constant after repeated
      injection. The results of this study showed that the crude OMP extracted from P.
      aeruginosa induced a significant protection in mice against Pseudomonas
      infections and could be used as a vaccine candidate.

PMID- 19093524
TI  - Paddy stems cutting energy and suggested blade optimum parameters.
AB  - A pendulum type impact shear test apparatus was designed and constructed to
      measure the energy required for cutting paddy stem. Experiments were carried out
      to determine the optimum values of blade bevel angle, oblique angle, tilt angle
      and blade cutting velocity for cutting paddy stem of Sepidrood variety. The
      results show that blade bevel angle of 28 degrees, oblique angle of 30 degrees,
      tilt angle of 35 degrees and blade velocity of 2.24 m sec(-1) are optimum.

PMID- 19093523
TI  - Effects of extremely low frequency electromagnetic fields on testes in guinea
      pig.
AB  - This study is carried out to measure the changes in testosterone hormone level
      and changes in testes tissue on 36 adult male Guinea pigs that divided to 6
      groups. Group A as control group exposed to nil Electromagnetic Field (EMF) for
      two hours per day for 5 days duration, group B exposed to 0.013 microT in 5 Hz to
      the Same duration period, group C exposed to 0.207 microT in 50 Hz in similar
      conditions, group D exposed for 4 h day(-1) for 5 days in 0.013 microT, group E
      tested in 0.207 microT as group D, group F used as controlled group exposed for
      four hours per day in nil electromagnetic field. Guinea pig blood was tested
      after 5 days. Then data analyzed by t-test. The results indicated a significantly
      difference between control group and tested group of four and two hours,
      testosterone level decreased (p < 0.001), also testes tissues were sampled and
      observed main tissue changes in some treatments.

PMID- 19093525
TI  - Mutation of Streptomyces griseoflavus in order to obtain high yield
      desferrioxamine producing fused cells.
AB  - Streptomyces griseoflavus PTCC 1130 was mutated by UV irradiation. Two mutants
      were obtained (C7031 and S7011). These two mutants were able to produce
      desferioxamine. Desferrioxamine was extracted from the culture broth of the two
      mutated strains and the thin layer chromatogram of the products showed the R(F)
      values of 0.461, 0.463 and 0.456 for S7011, C7031 and the standard, respectively.
      The protoplasts of mutated Streptomyces griseoflavus were isolated and fused
      together. Total numbers of 58 fusions were obtained and only 17 fusions showed
      significant resistance to sodium azide and crystal violet. In terms of production
      of desferrioxamine only fusion PF9 and PF10 increased 68.3 and 81.8%
      desferrioxamine production as compared to parent strain (PTCC 1130),
      respectively.

PMID- 19093526
TI  - Effect of different plant spacing on the production of cauliflower (Brassica
      oleraceae var. Botrytis) under the agro-climatic conditions of D.I. Khan.
AB  - A research project to evaluate the effect of different plant spacing on the
      production of cauliflower was conducted at Horticulture Research Area, Faculty of
      Agriculture, Gomal University, Dera Ismail Khan, NWFP, Pakistan. Six different
      plant spacing viz., 30, 35, 40, 45, 50 and 55 cm were used. The results revealed
      significant variations in all the parameters and amongst various plant spacing,
      45 cm spacing showed the best response for all the parameters. Maximum plant
      height (49.33 cm), curd diameter (19.13 cm), maximum curd weight (1.23 kg plant(
      1)) and yield (30.77 t ha(-1)) were recorded in the plots where the plants were
      spaced 45 cm apart.

PMID- 19093527
TI  - Study on lipid changes of leaves and fruits olive adapted to high temperature
      condition Inkhuzestan.
AB  - The present study investigated the quantitative changes of olive leaves and
      fruits lipid during fruit ripening in olive cv. Manzanillo and cv. Dezful. Total
      lipids were measured and analyzed fatty acids by gas chromatography (GC) in on
      and off years. Present results showed that; Major fatty acids of leaves and
      fruits were palmitic, oleic and linoleic acid. In spite of fruit, means total
      lipid of leave were significantly difference between on and off years; although
      total lipids and fatty acids increase during ripening but there are negative
      regression between palmitic and oleic acid content of leaves and fruits. Oleic
      and palmitic acid ratio to total fatty acid gradually increased in fruit and
      leave respectively. Fruit size of Dezful cv. smaller than Manzanillo cv. But its
      lipid amount was more than Manzanillo cv. Oleic content was equal in both fruit
      cultivar. Comparisons of these results with our previous results on Olive cv.
      zard from Guilan show those climate dose not have important effect on lipid
      accumulative and alternate bearing. But regard to saturated fatty acid of two
      mentioned cultivar in this research the result showed that it is higher than
      considerably in the Dezful and Manzanillo cv. The great amount of saturated fatty
      acids is a suitable character for plant grown in high temperature conditions.

PMID- 19093528
TI  - Effect of feeding frequency on non-carcass components and wholesale cuts of
      Iranian fat-tailed lambs.
AB  - This experiment was conducted to evaluate the effect of feeding frequency on non
      carcass components and wholesale cuts in fat-tailed ram lambs of the Varaminni
      breed (n = 30, BW = 30.6 +/- 3.47 kg). Animals were assigned to three
      experimental groups according to their initial live body weights in a completely
      randomized design. The lambs in three groups fed with a TMR ration based on live
      body weight. First group (control) fed one daily, second group (treatment) fed
      twice times daily and third treatment fed four times per day. Live body weights
      recorded at 21 days intervals. Moreover, four lambs from each group were
      slaughtered and carcass characteristics were measured. Final BW, total BW gain
      and ADG did not differ (p > 0.05). Tail fat content were significantly (p < 0.05)
      higher in control than those in experimental group. The other carcass
      characteristics were not significantly different in control with experimental
      groups. It was concluded that increase of feeding frequency in varaminni ram
      lambs (fat tailed lambs) resulted in decreased fat reservoirs thus may be
      beneficial for improving meet production and decrease in fat content of tail.

PMID- 19093529
TI  - Row spacing and inter row spacing effects on some agro-physiological traits of
      two common bean (Phaseolous vulgaris L.) cultivars.
AB  - An experiment was conducted to evaluate the effects of row spacing (RS) and inter
      row spacing (IRS) on some agro-physiological traits of 2 common bean (Phaseolous
      vulgaris L.) cultivars, at the agricultural research area, Faculty of
      Agriculture, University of Urmia, Iran during 2003. Experimental design was a
      factorial split-plot based on randomized complete block design with 3
      replications. The 30, 45 and 60 cm of RSs constituted the main plots and IRSs of
      5, 10 and 15 cm and cultivars of Derakhshan and Naz (determinate and
      indeterminate, respectively) were allocated to the sub plots. Obtained results
      showed that different RSs and IRSs affected the Grain Yield (GY). The highest GY
      was recorded at 30 cm RS (4.191 t ha(-1)) and 5 cm IRS (3.926 t ha(-1)). The
      number of pods plant(-1) (NPP), the number of grains plant(-1) (NGP) and grain
      weight plant(-1) (GWP) increased as a result of a decrease in the RS and IRS. In
      addition, it was observed that by increasing the RS and IRS the first pod trait
      had higher height. However, the Grain Protein Content (GPC) was not affected by
      the IRS and RS changes. On the other hand, Naz (indeterminate) had higher
      capability for the grain yield than Derakhshan (determinate) cultivar.

PMID- 19093530
TI  - Prevalence of Epstein-Barr virus type 1 in patients with chronic periodontitis by
      nested-PCR.
AB  - The present study evaluated the subgingival presence of Epstein-Barr virus type 1
      (EBV-1) in patients with chronic periodontitis with nested-PCR. Subgingival
      plaque samples from 61 patients with chronic periodontitis with Probing Depth
      (PD) > or = 6 and 40 healthy controls were collected by sterile curette. DNA was
      extracted. A nested Polymerase Chain Reaction (PCR) method determined presence of
      EBV-1. The study included 61 patients (34 women, 27 men; 24-69 years of age; mean
      43) and 40 periodontally health controls (22 Women, 18 men, 21-69 years in age;
      mean 41.35%). EBV type 1 was detected in 37 samples (60.7%) and 1 samples (2.5%)
      of chronic periodontitis patients and healthy subjects, respectively. This study
      demonstrated that EBV-1 infection is associated with the activity of chronic
      periodontitis.

PMID- 19093531
TI  - Spawning season of Argenteus (Euphrasen, 1788) in the Northwest of the Persian
      Gulf and its implications for management.
AB  - The spawning periodicity of silver pomfret, Pampus argenteus, was investigated in
      627 specimens (137 female and 490 male) collected monthly by trawl net from the
      Northwest the Persian Gulf for a one year period (March 2004 to February 2005).
      Seven maturity stages were recognized by Kesteven scale. The length at first
      maturity (LM50) was calculated as 192 mm in combined sex. The overall sex ratio
      (female: male) was 1:3. Fluctuations in the Gonadosomatic Index (GSI) values and
      percentage of mature specimens suggested prolonged spawning season from May to
      October. There were two spawning peaks, the first one between May and July and
      the second in October. It is concluded that Iranian waters (in Khuzestan
      province)are the main spawning and nursery grounds for silver pomfret in the
      Persian Gulf.

PMID- 19093532
TI  - Study of bacterial infections among the patients with suspected cutaneous
      leishmaniasis.
AB  - The main objective of this study was to evaluate the prevalence of secondary
      bacterial infections in the patients with cutaneous lesions. The patients
      admitted to leishmaniasis laboratory of faculty of health, Tehran university of
      medical sciences from October 2004 to June 2005 were subjected in this study.
      Clinical samples were analyzed using standard bacteriological and parasitological
      methods. One hundred seventy three patients were subjected to this study and
      leishmania was found in 84 (48.5%) cases. According to bacteriological
      experiments, 47 cases (55.9%) had been also infected by bacterial infections. The
      most prevalent bacterial isolates included group D Streptococcus (19.1%),
      Enterococcus spp. (19.1%) and Staphylococcus aureus (12.7%). The findings of
      current study indicated that the bacterial infections are still an important
      problem in the patients with cutaneous leishmaniasis and should be considered in
      treating these patients.

PMID- 19093533
TI  - Effect of residual yolk sac on growth, liver total lipids and serum total lipids
      in broiler chicks.
AB  - Two experiments were conducted to investigate the effect of the residual yolk sac
      on growth and total lipids in serum and liver of newly hatched broiler chicks. In
      each experiments 36 one day old broiler chicks (Lohmann) were allocated to three
      groups according to the status of the residual yolk sac; deutectomized (surgical
      ablation of the residual yolk sac, Y), sham operated (S) or intact chicks (I). Y
      chicks, when compared to S or I chicks, exhibited significant reduction in body
      weight gain during the 1st week of age. Feed intake was not significantly
      affected by removal of residual yolk sac. Removal of the residual yolk sac had no
      effect on serum total lipids and serum cholesterol during 8 days post-hatch and
      dietary fat absorption for 15 days. Significant interaction between age and
      removal of residual yolk sac was observed for liver total lipids. Furthermore,
      the results showed that the liver total lipids, serum total lipids and serum
      cholesterol were significantly lower at day 8 compared to day 2. The results of
      this study indicated that removal of the residual yolk sac had no effect on serum
      total lipids, serum cholesterol, dietary fat absorption and liver weight.
      However, it reduced the growth of the chicks for the first week of age, after
      which the chicks compensate for this reduction. The removal of the residual yolk
      sac showed significant interaction with age for liver total lipids.

PMID- 19093534
TI  - Functional and numerical responses of Stethorus gilvifrons Mulsant feeding on
      strawberry spider mite, Tetranychus turkestani Ugarov and Nikolski.
AB  - Laboratory experiments were conducted to measure the functional and numerical
      responses of Stethorus gilvifrons Mulsant feeding on Tetranychus turkestani
      Ugarov and Nikolski. Adult ladybirds were isolated singly for 24 h in 8 cm petri
      dishes with either 4, 8, 12, 24, 48 or 96 adult females of T. turkestani. Results
      showed a typical type 3 functional response, with up to 65.2 preys attacked when
      96 preys were provided. The rate of attack and handling time were 0.0012 and
      0.415 (days), respectively. The number of eggs deposited by the predator depended
      on the density of the prey; up to maximum of 223.6 eggs female(-1) at prey
      density of 96 spider mites were recorded. No eggs were laid at densities of 4 and
      8 prey/arena.

PMID- 19093535
TI  - Detection of probable effects of microwave exposure of blood parameters of RBC,
      PCV and Hb in rat.
AB  - The aim of this preliminary investigation was to assess the probable effects of
      microwave exposure on Hematological parameters of RBC (Red Blood Cell), PCV
      (Packed Cell Volume) and Hb (Hemoglobin) in rats. For this study 80 Sprague
      Dawley rats were exposed to 2450 MHZ microwave field for a period of one year.
      The experiment groups were divided to 5 groups, each 16 (8 males and 8 female), 4
      for treatment and one, for control (D, E, F, G and H). The incident power density
      of the first two experiment groups was 1 mW m(-2) and for next two groups, was 10
      mW cm(-2). The daily exposure time was 5 min for groups F and G and 30 min for
      groups, D and F. The animals in control group (H) were under normal condition
      without any microwave exposure. In the end of the study the blood samples were
      taken from the heart of animals under ether anesthesia and determination of blood
      parameters were performed by cell counter auto analyzer. According to the
      statistical results, the level of RBC in male groups of F and G and percentage of
      PCV in female and male groups of F and content of Hb, in female groups of F, were
      significantly increased in comparison to the control group and variation of
      results in other groups were not significant.

PMID- 19093536
TI  - In vitro efficacy for some local antimicrobial products against E. coli K12.
AB  - The aim of this study was to assess the in vitro activity of a number of
      antimicrobial agents (Sultrim, Oxytetracycline, enrofloxacin and florfenicol)
      produced by different Iranian manufacturers against E. coli K12. Comparison of
      the MICs of reference antimicrobials with Disk Diffusion (DD) results of
      different products made by Iranian manufacturers revealed that all products of
      tested antimicrobials seem to be in synergy with their reference MIC evaluation.
      Present data indicate that E. coli K 12 is resistant to Enrofloxacin (MIC value
      of 6.25 microg mL(-1)) by both MIC and DD evaluation.

PMID- 19093537
TI  - Cleft palate in a male water buffalo calf.
AB  - Congenital palatal defects are common in animals but there is only one report of
      water buffalo has been recorded in Iran. One died male water buffalo calf was
      examined after hysterotomy operation. At necropsy findings, brachygnathia, palate
      cleft and small lungs were diagnosed. It is the second report of water buffalo
      cleft palate in Iran.

PMID- 19093538
TI  - [The influence of CO2 molecular relaxation dynamics on photoacoustic signal in
      near infrared (NIR) range].
AB  - Photoacoustic spectroscopy (PAS) based on tunable diode laser (TDLPAS) is a
      widely recognised method for its excellent performance in trace gas monitoring
      and spectral analysis. This spectral technique provides many advantages such as
      high selectivity and sensitivity, on-line, real time and contactless measurements
      in a compact experimental arrangement. In the present paper, a resonant PA
      spectrometer based on a low-power near infrared distributed feedback (DFB) diode
      laser and a home-made resonant PA cell operating on its first longitudinal mode
      is developed, and the PA system has the advantage of simple experimental setup,
      easy operation, and low-cost, room temperature operating, etc. By investigating
      the performances of the PA cell at first, a good agreement was achieved between
      experimental and theoretical results; we have systematically investigated the
      influence of molecular relaxation effect on the PA detection of CO2 molecule near
      1.573 microm, and presented the relevant analysis in theory. The research result
      shows that the detection sensitivity of the system based on PAS technique can be
      effectively improved by using the molecular relaxation effect.

PMID- 19093539
TI  - [Effect of saturation and velocity selective population in 6S1/2 --> 6P3/2 laser
      excitation in Cs vapor mixed with Ar].
AB  - The excited state population distribution created by 6S1/2 --> 6P3/2 laser
      excitation in room temperature cesium vapor mixed with Ar was quantitatively
      analyzed applying absorption and saturation spectroscopy. A simple method for the
      determination of the excited state population in a single excitation step based
      on the measurements of the saturated and unsaturated absorption coefficients was
      tested. When the line profile is nearly pure Doppler and the laser linewidth is
      much smaller than the inhomogeneous linewidth but comparable with homogeneous
      linewidth, the fraction N(v(z)) of the atoms in the ground state that are able to
      absorb under inhomogeneous broadening conditions can be determined. The
      transmission of the medium in the center of the Doppler envelope of the strong h.
      f. component of the CsD2 line due to hyperfine pumping alone amounts to
      approximately 5%. The assumption that has been made is that the lower-state
      hyperfine levels are populated in a statistical ratio. The absorption
      coefficients were measured for a series of P852 powers between 20 microW and 2. 5
      mW. The velocity selective population density in the 6P3/2 state was obtained.
      The population in the 6P3/2 level obtained from the saturation measurements was
      also determined by the absorption measurement of narrow spectral line from a Cs
      hollow cathode lamp. The agreement between the results obtained in these two ways
      is very good. It was shown that 5% of the ground state population could be
      transferred to the first excited state by pumping the Doppler broadened line with
      a single-mode narrow-band laser. The argon caused line broadening and therefore
      increased the effective pumping rate in the first excitation step. The dependence
      of the 852 nm line fluorescence intensity was plotted against the population in
      the 6P3/2 level determined from the saturation absorption. This can serve as
      confirmation of the reliability of the method used for the determination of the
      excited state population.

PMID- 19093540
TI  - [White-light source spectral domain OCT based on partial spectrum analysis].
AB  - In order to enhance the longitudinal resolution and the signal to noise ratio
      (SNR) of spectral domain OCT (SDOCT), a SDOCT using white light source was
      developed. By analyzing the relationship among axial total number of pixels in
      the horizontal direction of CCD, the spectrum of white-light source and
      longitudinal resolution, a white-light source SDOCT (WSSDOCT) based on partial
      spectrum analysis was developed and introduced. With proper white light source
      required and band width for detection selected, the SNR was improved with maximum
      detecting depth and high longitudinal resolution guaranteed. Experimental results
      validate the measurement method for the coherence length of the light source, and
      system & image longitudinal resolution, and also testify the feasibility of
      WSSDOCT.

PMID- 19093541
TI  - [Analysis of visible extinction spectrum of particle system and selection of
      optimal wavelength].
AB  - In the total light scattering particle sizing technique, the extinction spectrum
      of particle system contains some information about the particle size and
      refractive index. The visible extinction spectra of the common monomodal and
      biomodal R-R particle size distribution were computed, and the variation in the
      visible extinction spectrum with the particle size and refractive index was
      analyzed. The corresponding wavelengths were selected as the measurement
      wavelengths at which the second order differential extinction spectrum was
      discontinuous. Furthermore, the minimum and the maximum wavelengths in the
      visible region were also selected as the measurement wavelengths. The genetic
      algorithm was used as the inversion method under the dependent model The computer
      simulation and experiments illustrate that it is feasible to make an analysis of
      the extinction spectrum and use this selection method of the optimal wavelength
      in the total light scattering particle sizing. The rough contour of the particle
      size distribution can be determined after the analysis of visible extinction
      spectrum, so the search range of the particle size parameter is reduced in the
      optimal algorithm, and then a more accurate inversion result can be obtained
      using the selection method. The inversion results of monomodal and biomodal
      distribution are all still satisfactory when 1% stochastic noise is put in the
      transmission extinction measurement values.

PMID- 19093542
TI  - [Study of complex accelerating layer in SSCL].
AB  - Solid state cathode luminescence (SSCL) is a bran-new excitation mode. In the
      device, the inorganic semiconductor is used for electron acceleration. After
      acceleration the energy of electrons may be raised up so high that these hot
      electrons have enough energy to induce luminescence in the visible region by
      impact excitation. It is a new development and application of the traditional CRT
      theory in solid organic/inorganic electroluminescence device, and it is a new
      method to improve the EL efficiency. a new phenomenon of co-existence of
      different mechanisms of excitations in addition to these kinds of excitations. It
      is very important that all these effects are additive, amplifying or compensatory
      and reinforce the luminescence intensity and make the spectrum of luminescence
      wider. The accelerating layer of SSCL is the important part of improving the
      performance of SSCL devices, in which electrons can be accelerated to hot
      electrons with high energy and obtain electron multiplication. It is the key to
      improving the performance of SSCL devices, enhancing injecting electrons to
      increase hot electrons. So we prepared the complex accelerating layer with SiO2,
      ZnS and ZnO, giving attention to acceleration and injecting property. Firstly, we
      respectively prepared the devices with the polymer MEH-PPV and SiO2, and ZnS, and
      ZnO, and found that SiO2/ZnS and ZnO/SiO2 are better. And then contrasting them,
      we found SiO2/ZnS is better. It's because that ZnS and ZnO are similar in
      injecting property, but ZnS is evidently better than ZnO in electron
      multiplication. SiO2 is the primary accelerating layer, and ZnS can lower the
      voltage barrier by ladder voltage barrier. Finally, we found that this complex
      accelerating layer, especially in high electric field, can increase the
      efficiency of SSCL devices by increasing initial electrons and hot electrons.

PMID- 19093543
TI  - [Detection of metal ions in water solution by laser induced breakdown
      spectroscopy].
AB  - Environmental concerns about the hazardous heavy metals in seawaters have been
      greatly increased in these years. To evaluate the potential application of laser
      induced breakdown spectroscopy (LIBS) to on-line toxic metals pollution
      monitoring in ocean, some experimental investigations with LIBS technique to
      detect metal ions in CuSO4 and Pb(NO3)2 water solutions have been carried out in
      our laboratory. A Q-switched Nd:YAG laser operating at 532 nm with pulse width of
      10 ns and repetition frequency of 10 Hz was utilized to generate plasma on a
      flowing liquid surface. The ensuing plasma emission was coupled by a quartz lens
      to a double grating monochromator and recorded with a PMT in conjunction with a
      computer controlled boxcar integrator. The temporal characteristic of the laser
      induced plasma and the power dependence of LIBS signal were investigated. The
      operation condition was improved with the optimal ablation pulse energy and the
      delay time for LIBS signal detection. The ablation location was varied to achieve
      better LIBS signal. The optimized ablation location for lead was found to be
      different from that for copper due to the breakdown of the ambient air. The
      detection limit of metal ion in water solution under the optimized operation
      conditions was found to be 31 ppm for copper and 50 ppm for lead. The
      experimental results proved that the flexibility of LIBS has the potential to be
      applied to the detection of toxic metals in seawaters, but the limits of
      detection for each element should be improved further to make a practical
      application of LIBS in this field.

PMID- 19093544
TI  - [Study on decomposition products of methanol in AC discharge by spectroscopy].
AB  - The intermediate decomposition products of methanol (CH3OH) in an AC discharge
      were diagnosticated via concentration modulation spectroscopy. Several main
      vibrational bands of CO Angstrom beta 1 sigma+ -alpha 1pi system, CH alpha 2
      delta-X2pi system at 430 nm and beta 2 sigma- -X2pi at 390 nm, as well as CHO
      (329.82 nm), CH2O (369.8 nm), CH3O (347.8 nm) and Balmer series spectra of H atom
      were identified in the region between 300 and 670 nm. Furthermore, the
      dependences of the emission spectral intensities of the intermediate
      decomposition products on the discharge voltage and parent gas pressure were
      investigated in detail. The experiments indicated that the relative population
      ratio of CO (beta 1 sigma+) and H increases with increasing discharge voltage
      more quickly than that of CH (alpha 2 delta). Several possible reaction passages
      were given and discussed. Additionally, the vibrational and rotational
      temperatures of CH (alpha 2 delta) were determined to be about 4200 and 1100 K
      respectively, and the vibrational temperatures of CO (beta 1 sigma+) were
      determined to be about 2500 K by analyzing the intensity distribution using
      LIFEBASE computer program. The decomposition mechanism of methanol in the
      discharge plasma was discussed as well.

PMID- 19093545
TI  - [Compatible low target feature coatings].
AB  - Indium tin oxide (ITO) film has low reflectance in near infrared band while high
      reflectance in infrared band, and its dielectric constant can be described by
      Drude free-electron model. SiO film has very strong absorption at certain
      infrared wavelength By combining them, certain spectral selectivity can be
      realized. In the present paper, the authors investigated SiO/ITO films in terms
      of spectrum selectivity, and discussed the influence of film structure on
      reflection spectrum. By means of the computation of reflection spectrum with
      characteristic matrix, the authors found that SiO/ITO film can be used as a
      compatible infrared low target feature coating by properly adjusting film
      arrangement and selecting suitable film parameters.

PMID- 19093546
TI  - [Quantitative analysis of nucleotide mixtures with terahertz time domain
      spectroscopy].
AB  - Adenosine, thymidine, guanosine, cytidine and uridine form the building blocks of
      ribose nucleic acid (RNA) and deoxyribose nucleic acid (DNA). Nucleosides and
      their derivants are all have biological activities. Some of them can be used as
      medicine directly or as materials to synthesize other medicines. It is meaningful
      to detect the component and content in nucleosides mixtures. In the present
      paper, components and contents of the mixtures of adenosine, thymidine,
      guanosine, cytidine and uridine were analyzed. THz absorption spectra of pure
      nucleosides were set as standard spectra. The mixture's absorption spectra were
      analyzed by linear regression with non-negative constraint to identify the
      components and their relative content in the mixtures. The experimental and
      analyzing results show that it is simple and effective to get the components and
      their relative percentage in the mixtures by terahertz time domain spectroscopy
      with a relative error less than 10%. Component which is absent could be excluded
      exactly by this method, and the error sources were also analyzed. All the
      experiments and analysis confirms that this method is of no damage or
      contamination to the sample. This means that it will be a simple, effective and
      new method in biochemical materials analysis, which extends the application field
      of THz-TDS.

PMID- 19093547
TI  - [Relationship between temperature range and wavelength bandwidth for multi band
      pyrometry].
AB  - In the present paper, based on the linearity spectral emissivity model with two
      parameters in the narrow investigated waveband, we extend tri-wavelength
      pyrometry to tri-band pyrometry through waveband measurements of radiation
      temperature. In tri-band pyrometry, in order to realize the non-distortion
      measurement, considering the effect of the dynamic range and the minimum
      sensibility of the sensor on the coupling relation of multi-channel signals, the
      restriction condition of the effective temperature measurement range is
      discussed. However, under the assumption of the fixed sensor parameters, the
      measurement bandwidth of the sensor is an important influencing factor to the
      effective temperature measurement range in applications of tri-band pyrometry.
      Then for the measured objects with the known radiation characteristics, the
      variation of the effective temperature measurement range with the bandwidth of
      the sensor is presented through numerical simulations. So the required condition
      of bandwidth of the sensor is theoretically determined through the above
      discussions of the effective temperature measurement range. The analyses in this
      paper may provide the necessary theoretical guides to the design of the sensor of
      radiation temperature measurement.

PMID- 19093548
TI  - [Morphology determination of multi-needle-to-plate positive corona discharge].
AB  - Using the method of OES (optical emission spectrum) for measuring N2 emission
      spectrum, the distribution of the energetic electrons in multi-needle-to-plate
      positive corona discharge at atmospheric pressure was investigated, and compared
      with that in negative corona discharge. According to the distribution of N2
      second positive band's intensity I(SPB), the outline of the ionization region in
      glow discharge and the streamer channel were drawn rather accurately. The
      relationship between I(SPB) and the discharge current I in glow discharge can be
      obtained through the volume integral of the I(SPB). In glow discharge, both the
      ionization region scale and I(SPB) are smaller than in negative corona discharge,
      the electron avalanche develops farther along the radius direction of needle than
      along axis direction, and only the arrange along axis direction is enhanced
      slightly with the rise of the applied voltage U. The integral of I(SPB) is second
      order linear to I. In streamer discharge, the discharge channels develop from
      needlepoint to the plate, while the shape of the region in which I(SPB) is higher
      looks like a bullet. The density of energetic electron in the channel farther
      away from the needlepoint is relatively uniform along the axis direction, but
      first increases then decreases along the radius direction.

PMID- 19093549
TI  - [The study on the characteristics and particle densities of lightning discharge
      plasma].
AB  - According to the wavelengths, relative intensities and transition parameters of
      lines in cloud-to-ground lightning spectra obtained by a slit-less spectrograph
      in Qinghai province and Xizang municipality, and by theoretical calculations of
      plasma, the average temperature and electron density for individual lightning
      discharge channel were calculated, and then, using Saha equations, electric
      charge conservation equations and particle conservation equations, the particle
      densities of every ionized-state, the mass density, pressure and the average
      ionization degree were obtained. Moreover, the average ionization degree and
      characteristics of particle distributions in each lightning discharge channel
      were analyzed. Local thermodynamic equilibrium and an optically thin emitting gas
      were assumed in the calculations. The result shows that the characteristics of
      lightning discharge plasma have strong relationships with lightning intensities.
      For a certain return stroke channel, both temperatures and electron densities of
      different positions show tiny trend of falling away with increasing height along
      the discharge channel. Lightning channels are almost completely ionized, and the
      first ionized particles occupy the main station while N II has the highest
      particle density. On the other hand, the relative concentrations of N II and O II
      are near a constant in lightning channels with different intensities. Generally
      speaking, the more intense the lightning discharge, the higher are the values of
      channel temperature, electron density and relative concentrations of highly
      ionized particles, but the lower the concentration of the neutral atoms. After
      considering the Coulomb interactions between positive and negative particles in
      the calculations, the results of ionization energies decrease, and the particle
      densities of atoms and first ionized ions become low while high-ionized ions
      become high. At a temperature of 28000 K, the pressure of the discharge channel
      due to electrons, atoms and ions is about 10 atmospheric pressure, and it changes
      for different lightning stroke with different intensity. The mass density of
      channel is lower and changes from 0.01 to 0.1 compared to the mass density of air
      at standard temperature and pressure (STP).

PMID- 19093550
TI  - [Hyperspectral remote sensing image classification based on radical basis
      function neural network].
AB  - Based on the radial basis function neural network (RBFNN) theory and the
      specialty of hyperspectral remote sensing data, the effective feature extraction
      model was designed, and those extracted features were connected to the input
      layer of RBFNN, finally the classifier based on radial basis function neural
      network was constructed. The hyperspectral image with 64 bands of OMIS II made by
      Chinese was experimented, and the case study area was zhongguancun in Beijing.
      Minimum noise fraction (MNF) was conducted, and the former 20 components were
      extracted for further processing. The original data (20 dimension) of extraction
      by MNF, the texture transformation data (20 dimension) extracted from the former
      20 components after MNF, and the principal component analysis data (20 dimension)
      of extraction were combined to 60 dimension. For classification by RBFNN, the
      sizes of training samples were less than 6.13% of the whole image. That
      classifier has a simple structure and fast convergence capacity, and can be
      easily trained. The classification precision of radial basis function neural
      network classifier is up to 69.27% in contrast with the 51.20% of back
      propagation neural network (BPNN) and 40. 88% of traditional minimum distance
      classification (MDC), so RBFNN classifier performs better than the other three
      classifiers. It proves that RBFNN is of validity in hyperspectral remote sensing
      classification.

PMID- 19093551
TI  - [Sensitivity study of a revised leaf photochemical reflectance index (PRI)].
AB  - Photochemical reflectance index (PRI) defined as a normalized difference index
      using two narrow reflectance bands at 531 and 570 nm that are closely related to
      xanthophyll cycle pigment content has been successfully used to estimate leaf
      photosynthetic light use efficiency (LUE) across species which vary in water
      content and nitrogen concentration. Previous research demonstrated that a
      consistent relationship could be established between PRI and LUE calculated from
      gas exchange measurements at the leaf, small canopy, and full forest or crop
      canopy scales. However, a number of problems, such as the saturation of PRI when
      LUE exceeds 0.03 mol CO2 mol(-1) PPED (photosynthetic photon flux density) and
      disjunctive relationships of PRI and LUE in seasonal changes, still existed and
      need to be handled in order to evaluate LUE more accurately. A sensitivity study
      of a revised PRI with four leaf parameters was performed based on PROSPECT model
      in the present article to study the effects of different biochemical
      concentrations on leaf SR-PRI (simple ratio PRI). Sensitivity study proved that
      leaf SR-PRI is more sensitive to leaf mesophyll structure parameter (N) and
      chlorophyll a + b content (c(ab)) than parameters of dry matter content (c(m))
      and equivalent water thickness (c(w)), indicating that leaf mesophyll structure
      parameter (N) and chlorophyll a + b content (c(ab)) should be especially
      considered when acquiring leaf SR-PRI. And changes in the two parameters would
      cause large variation in SR-PRI which would reduce the precision for estimating
      light use efficiency. Validation study of SR-PRI was carried out in the analysis
      and the results proved that SR-PRI can also be a feasible index of estimating LUE
      for four species of plants with correlation coefficients better than that of PRI
      and LUE. The advantage of SR-PRI compared to PRI is its much clearer physical
      meaning and its sensitivity to the changes in reflectance at 531 nm which serves
      as a core parameter to evaluate light use efficiency.

PMID- 19093552
TI  - [The theory and the influential factors of laser induced breakdown spectroscopy].
AB  - The laser-induced breakdown spectroscopy (LIBS) technique, due to its lack of
      pretreatment of the material and the speed of analysis, has shown a great
      potential for a wide range of industrial applications. The current situation of
      application and study of LIBS are reviewed. Meanwhile, the laser used to explode
      the Cr and Co film had a pulse duration of 10 ns, the highest single pulse energy
      was 50 mJ at a repetition rate of 20 Hz, and a wavelength of 1064 nm. When the
      excitation energy was less than 10 mJ, there was little difference in spectral
      signal excited by different energy for Cr film. Otherwise, the signal showed
      obvious change when excitation energy was higher than 10 mJ. The principle,
      characters, history and recent trend of LIBS were introduced systematically. The
      factors influencing LIBS performances, including the characteristic of laser,
      delay time, experiment setting, the kind and the pressure of surrounding. Gas,
      single or dual pulse, and the analysis method were analyzed.

PMID- 19093553
TI  - [Study of lanthanide complexes-doped silica gels and the Co-fluorescence effect
      by photoacoustic spectroscopy in situ].
AB  - Silica matrices, due to their good optical, thermal and chemical properties, are
      suitable candidates for the hosts of luminescent lanthanide complexes. However,
      lanthanide complexes would be unstable in the most common sol-gel precursor
      solution. It is important to study the coordination environment of lanthanide
      ions and the formation of lanthanide complexes in silica gels. In the present
      work, lanthanide complexes Ln(Sal)3 x H2O(Ln3+:La3+, Nd3+ and Tb3+; Sal:salicylic
      acid) were incorporated into silica gels via a sol-gel process. PA technique was
      firstly used to monitor the formation of lanthanide complexes in silica gels.
      Upon heat treatment at 110 degrees C, PA intensity of the ligand increased for
      Tb3+, La3+ and Nd3+ complexes in silica gels, respectively, while this difference
      could not be observed for the wet gels (samples without heat treatment). By
      comparison with fluorescence spectra, experimental data indicate that lanthanide
      complexes decompose in wet gels. The formation of lanthanide complexes in silica
      gels is discussed from two aspects: radiative and nonradiative processes. Co
      luminescence effect was found for lanthanide complexes with aromatic carboxylic
      acid doped silica gels for the first time. For Tb0.8 Ln0.2 (Sal)3 x H2O
      (Ln3+:Gd3+ or Nd3+)-doped silica gel, the addition of Gd3+ increased the
      luminescence efficiency of Tb3+, while the luminescence of Tb3+ was quenched
      remarkably with the addition of Nd3+. Possible mechanism behind the co
      luminescence phenomena of lanthanide complexes-doped silica gels is discussed.

PMID- 19093554
TI  - [Structure and luminescence properties of ZnO films prepared by RF magnetron
      sputtering].
AB  - ZnO thin films with c-axis preferred orientation were prepared on glass
      substrates by radio frequency co-reactive magnetron sputtering technique, and the
      effect of the substrate temperature on the microstructure and the luminescence
      properties of the ZnO thin films was studied by X-ray diffractometry (XRD),
      scanning probe microscopy(SPM)and fluorescence spectrophotometer. The XRD
      patterns of the four ZnO samples prepared at different substrate temperatures
      were measured by XRD. figure which embodied the relation of full wave at half
      maximum (FWHM) and grain size of the four samples as a function of substrate
      temperatures was given out, too. It was concluded that the crystallization of the
      samples was promoted by appropriate substrate temperatures, the results consist
      with the AFM microscopic photos of the two samples. In addition, the
      photoluminescence (PL) spectra of the four samples were measured at room
      temperature. Violet peak located at about 400 nm, blue peak located at 446 nm and
      green peak located at about 502 nm were observed from the PL spectra of the four
      samples. With the rise of the growth temperature, the intensity of the violet
      peak and the blue peak increased sharply, and the intensity of green peak
      increased at the same time. It was concluded that the violet peak may correspond
      to the exciton emission, the blue peak was mainly attributed to the interstitial
      Zinc (Zn(i)) and the green emission peak must be related to the deep level
      defects of oxygen (Vo) in the crystal of ZnO films. Absorption property of the
      samples were researched by UV spectrophotometer, and the absorption spectrum of
      the film deposited at 150 degrees C and the (alpha h nu)2 versus h nu of the ZnO
      thin film were given. From the absorption spectrum, it could be observed that the
      spectroscopic data in UV region showed split peak and shoulder peak. With
      analysis of the absorption spectrum of the sample deposited at 150 degrees C, it
      was proved that our analysis of the photoluminescence mechanism was reasonable.

PMID- 19093555
TI  - [Comparative study on photoluminescence from Ge/PS and Ge/SiO2 thin films].
AB  - Ge thin films were deposited on porous silicon substrate using the RF magnetron
      sputtering technique with Ge target and sputtering for 4, 8 and 12 min
      respectively. Ge-containing silicon oxide thin films were deposited on n-type Si
      substrate using the RF magnetron sputtering technique with a Ge-SiO2 composite
      uarget and with Ge wafer in the target having percentage areas of 5%, 15% and
      30%, respectively. These samples were annealed in a N2 atmosphere at 300 degrees
      C, 600 degrees C and 900 degrees C for 30 min. A comparative study of
      photoluminescence from Ge/PS and Ge/SiO2 thin films is reported. The FTIR was
      used to research the structure of Ge/PS thin films. The FTIR showed that the Si
      Hx (x = 1-3) absorption peaks disappeared, but Si-O-Si, Si2O-SiH and H2Si-O2
      absorption peaks were enhanced, and the surfaces of Ge/PS thin films have formed
      a goodish integrated cross-linked Si-O-Si network. It was indicated that Ge thin
      films deposited on porous silicon can improve the level of oxidation. At the same
      time, the Si-O and Si-Si bonds on the surface of PS thin films were broken, but
      some new bands such as Si-Ge, Ge-Ge and Ge-O formed. As the results of the
      experiment showed that the photoluminescence peaks of Ge/PS thin films were
      located at 517 nm, the sputtering time influenced the intensity of light-emission
      remarkably and with increasing the thickness of Ge layer coated, the intensity of
      light-emission dropped abruptly. When Ge sputtered for 12 min, the photolumines
      cence peak almost disappeared. The photoluminescence peaks of Ge/SiO2 thin films
      were located at 580 nm, the percentage areas of Ge wafer in the target influenced
      the intensity of light-emission obviously, and with increasing the percentage
      area of Ge wafer in the sputtering target, the photoluminescence intensity was
      reduced greatly. Though with increasing the annealing temperature of different
      thin films, all the photolu minescence spectra from Ge/PS and Ge/SiO2 thin films
      changed scarcely, and our explanation is that Ge-related defects at the
      interfaces between PS and the Ge nanocrystals embedded in the pores were
      responsible for the photoluminescence of Ge/PS thin films. However, the
      photoluminescence of Ge/SiO2 thin films' light emission originates from
      luminescence centers in Si oxide films. Ge/PS and Ge/SiO2 thin films both
      contained Ge nanocrystals and silicon oxide layer, and have similar structure,
      however, they have different mechanism behind photoluminescence. The experimental
      results have been explained reasonably.

PMID- 19093556
TI  - [Formation of W/O microemulsions in TBP-Pd(II)-HCl extraction system and
      spectroscopic research on the evolution of solution aggregation structure].
AB  - The formation of W/O microemulsions in the extraction system TBP-Pd(II)-HCl was
      investigated. The solution structural evolution of the palladium loaded organic
      phases, with the variation in the content of acid into the organic phases, was
      characterized by various spectroscopic techniques such as DLS, FTIR and 31P-/1H
      NMR. The results indicated that (1) the extraction behaviors of palladium was
      related to the formation of W/O microemulsion structure in the loaded organic
      solutions. Because of the co-extraction of hydrochloric acid, there formed the
      microscopic aggregates in the loaded organic phases. (2) The variation in the HCl
      content in organic phase resulted in corresponding changes in solution structure.
      With the increase in the HCl content, the average radii of nanoscopic aggregates
      in the organic phases increased and then decreased. The extraction of HCl into
      the organic phase exhibited a distinct impact on the O-H stretching vibration and
      O-H-O bending vibration of water molecules in the microscopic W/O micelles. FTIR
      spectra of the organic phase saturated with acids show that the broad band of O-H
      stretching vibration of water extended to a very wide range and overlaped with
      the C-H stretching vibration bands. The higher the acid concentration in the
      organic phase was, the greater the overlapping. On the other hand, it was also
      observed that a remarkable change appeared in the O-H-O bending vibration of
      water and the stretching vibration of P=O in TBP molecules shifted to lower
      frequency. With the increase in acid content in the TBP organic phases, the
      observed 31P NMR chemical shifts decreased and varied to up-field; whereas the 1H
      NMR chemical shift of H+ increased and even became larger than that of deuterium
      chloride-d at a lower frequency field. The changes in delta 31P to opposite
      direction of delta H+ means that TBP molecules were associated with acid protons
      and water molecules in microemulsion pools to form RP=O x H+ or RP=O x H3O+, and
      then interacted with PdCl4(2-) complex ions, which finally led to the extraction
      of palladium into the organic phase. (3) When forming the W/O reversed
      micelles/microemulsions, the concentration of acid within the microscopic
      micelles was even higher than that of saturated concentrated hydrochloric acid.
      It was the microscopic structural changes in organic phase microemulsion "water
      pool" that resulted in the corresponding variations in the palladium extraction
      behaviors.

PMID- 19093557
TI  - [In-situ FTIR study of CO adsorption on Co-Mo/Al2O3 hydrodesulphurization
      catalysts].
AB  - Due to the implementation of more stringent specifications in sulfur content for
      diesel oil, a deep understanding of the active phase of Co-Mo/Al2O3 catalysts is
      necessary to the development of ultra-deep hydrodesulphurization (HYD) catalysts.
      A series of reductive Co-Mo/Al2O3 catalysts prepared in the lab and the high
      active industrial catalyst (G) were studied by in-situ FTIR using CO as probe
      molecule. The showed a good relationship with the desulphurization activities of
      the catalysts. With the increase in MoO3 and CoO loading, the desulphurization
      activity of catalyst increases, and the infrared spectrum changes with the amount
      of CO adsorbed on the catalyst. There is a new band at 2179 cm(-1) when the MoO3
      loading is up to 20% and CoO up to 4. 16%. According to the activities of the
      catalysts, the appearance of this new band suggests that the catalyst has higher
      hydrodesulphurization (HYD) activity. Compared with the infrared spectrum of CO
      on the catalyst of the same MoO3 and CoO loading by the common preparation
      method, the catalyst prepared with chelating agents has higher HYD activity and
      its band at 2 179 cm(-1) is stronger. The infrared spectrum of CO adsorbed on
      optimum Co-Mo/Al2O3 catalyst prepared in the lab is similar to the highly active
      industrial catalyst (G). Their bands at 2179 cm(-1) are both very strong and
      their HYD activities are both higher than the others. Thus, the appearance and
      the increase of the band at 2179 cm(-1) indicate the increase in the HYD activity
      of Co-Mo/Al2O3 catalysts to some extent, which could be an effective tool for
      developing ultra-deep HYD catalysts.

PMID- 19093558
TI  - [Investigation on effect of PVP on morphological changes and crystallization
      behavior of nylon 6 in PVP/nylon 6 blends by FTIR spectroscopy].
AB  - Temperature-dependent FT IR, DSC and POM were used to investigate the interaction
      between PVPK90 and nylon 6 molecules and its effect on the thermal behavior and
      morphology of nylon 6. DSC results suggest that the melting and crystallization
      behavior of nylon 6 are obviously influenced by the introduction of PVP. With the
      PVP content increasing, the crystallization temperature, melting temperature and
      the crystallinity of nylon 6 decreased, and eventually, both the exothermal and
      endothermic peaks could not be observed when the PVP content reached 80%,
      implying that the aggregation structure of nylon 6 changes from the crystalline
      state to the amorphous state. FTIR provided the evidence of the interaction
      between PVP and nylon 6 molecules. With the increase in PVP content, the peak
      position of nu N-H of nylon 6 gradually shifts from 3311 to 3300 cm(-1) with 90%
      content of PVP, and the half height peak width is broadened correspondingly.
      Three peaks were obtained in the carbonyl group absorption band for PVPK90/Nylon
      6(50/50) and PVPK90/Nylon 6(80/20) blends from the curve-fitting results. With
      the addition of PVP molecules, the nu C=O of nylon 6 shifts to higher wave number
      and a new peak located at about 1620 cm(-1) appears and its peak area increases
      with the content of PVP. The above spectral variation of nu C=O and nu N-H in the
      PVPK90/Nylon 6 blend indicates that the carbonyl group of PVP could form H
      bonding with N-H group of nylon 6 molecule, and partially destroy the hydrogen
      bonding between the nylon 6 molecules. POM results showed that the spherulitic
      size of nylon 6 decreases with the increment of the PVP and becomes more
      imperfect, and when the PVP content reaches 80%, no spherulites could be
      observed. This phenomenon is attributed to the molecular interactions between the
      PVP and the nylon 6 molecules, which weakens the free mobility of nylon 6 chains
      to form regular packing and eventually induces the change in the spherulitic
      morphology of nylon 6. In summary, the molecular interactions between the
      carbonyl group of PVP molecules and N-H group of nylon 6 molecules account for
      the above changes in the crystalline structure and the morphology of nylon 6 in
      the blends.

PMID- 19093559
TI  - [Preparation of palladium nanoparticles by laser ablation and its spectral
      properties study].
AB  - Palladium colloid was obtained via laser ablation under 1064 nm excitation from
      an Nd:YAG laser in redistilled deionized water. The Pd colloid consisted of
      "chemically pure" Pd nanoparticles, which were free from extraneous ions or other
      chemicals since no chemical reaction was involved in the preparation. There was
      no characteristic peak in UV/Vis spectrum of Pd colloid in the region of 200-800
      nm. Hence, in contrast to the Au and Ag nanoparticles, the average size and the
      size distribution of the Pd nanoparticles could not be estimated from their
      UV/Vis adsorption spectral features. After the laser ablation, one drop (50
      microL) of Pd colloid was deposited on the aluminum plate and dried naturally to
      form the Pd island films. This method resulted in the formation of a rough
      surface with a large number of separated Pd islands 20 microm in diameter.
      According to the SEM measurement, Pd nanoparticles with the average diameter of
      approximately 200 nm formed Pd island films. Surface-enhanced Raman scattering
      (SERS) activity of Pd colloid and Pd island films was evaluated by using 4
      mercaptopyridine (4MPY) as a probe molecule. The SERS study revealed that Pd
      island film was a highly efficient SERS-active substrate while there was no SERS
      signal observed from Pd colloid. The surface enhancement factor of Pd island
      films for 4MPY was estimated, which could reach values as high as 8. 7 X 10(4)
      under 632.8 nm excitation. This value was comparable with the largest value of
      10(4) cited in the literature. The SERS spectra of 4MPY molecules adsorbed on Pd
      surface showed that 4MPY molecules probably tilted from the Pd nanoparticle
      surface-via sulphur. By contrast, SERS spectrum of 4MPY adsorbed on Ag island
      films was recorded and analysed. From SERS data it was inferred that 4MPY
      molecules assumed the standing up orientation on the silver nanoparticle surface.
      It could be concluded that the 4MPY molecules were more perpendicular to the
      silver nanoparticle surface than to the Pd nanoparticle surface.

PMID- 19093560
TI  - [DSC and FTIR study of adsorbed lysozyme on hydrophobic surface].
AB  - During a process of hen egg white lysozyme adsorption and folding on a moderately
      hydrophobic surface (PEG-600), the effects of salt((NH4)2SO4) concentrations,
      surface coverage and denaturant (guanidine hydrochloride, GuHCl) concentrations
      on thermal stability and the changes in the molecular conformation of adsorbed
      native and denatured lysozyme without aqueous solution were studied with a
      combination of differential scanning calorimetry (DSC) with FTIR spectroscopy.
      The results showed that temperature due to endothermic peaks was reduced and the
      disturbance increased at higher temperature with the increase in salt
      concentration and surface coverage of adsorbed protein. beta-Sheet and beta-Turn
      stucture increased while alpha-Helix structure decreased after the adsorption.
      The peaks corresponding to both C-C stretching frequency in 1400-1425 cm(-1) and
      amide I band frequency in 1650-1670 cm(-1) of adsorbed denatured lysozyme can be
      detected in FTIR spectra while that due to amide I band frequency of adsorbed
      native lysozyme almost can't be observed. Adsorption resulted in structural loss
      of adsorbed native lysozyme, whose performance was less stable.

PMID- 19093561
TI  - [Research on predicting the qualities of stem of alfalfa hay by near infrared
      reflectance spectroscopy].
AB  - The present research was attempted to predict the qualities of stem of alfalfa
      (Medicago sativa L. ) without separation from the whole plant by near infrared
      reflectance spectroscopy and discussed the feasibility of using the near infrared
      reflectance spectra information of the whole object to predict the qualities of a
      certain part. Sixty six whole alfalfa hay samples of separated stems from leaves
      were collected and they were distinguishing by years, cultivars, cuts and growing
      periods. There were 138 calibration samples and 60 validation samplers. Fourier
      transform-near infrared reflectance spectroscopy (FT-NIRS) and partial least
      square (PLS) were used to set up the calibration models of stem's crude protein
      (CP), neutral detergent fiber (NDF), acid detergent fiber (ADF), crude ash (CA)
      and in vitro digestible dry matter (IVDDM) contents. All models showed great
      calibration and prediction performances except the one of stem's NDF content. The
      correlation coefficients of cross-validation (rCV) were between 0.8523 and
      0.9007, the root mean square errors of cross-validation (RMSECV) were between
      0.72% and 3.96% and the correlation coefficients of NIRS values and chemical
      values (r) were between 0.9255 and 0.9512. However, rCV, RMSECV and r of the
      model of stem's NDF content were 0.8214, 3.70% and 0.9020, respectively. It
      wasn't exact enough and would be used for rough predicting only. All of the
      results showed that near infrared reflectance spectra information of whole
      alfalfa hay could be used to predict some components of its stem exactly. It was
      the maiden attempt of using near infrared reflectance spectra information of the
      whole objects to evaluated the qualities of a certain part.

PMID- 19093562
TI  - [Theory and correction of interference fringe in static fourier transform
      spectrometer].
AB  - According to the requirement of spectrometer design, including high-speed,
      simplified structure, convenient fabrication and real-time measurement, a static
      Fourier transform spectrometer (SFTS) was introduced and its theory was derived
      and analyzed. In order to solve the correction problem of tilting interference
      fringe in the adjustment process of SFTS, mathematical derivation of the model of
      interference fring was systematically summarized. Meanwhile, the mathematical
      relationship between the rotation parameter of tilting mirror and the minimum
      clear aperture and that between the rotation parameter of tilting mirror and the
      rotation parameter of interference fringe were obtained by mathematical
      derivation. Besides, by using Matlab, the model of interference fringe was
      simulated, and the correction formula for monochromatic light was proofed. The
      simulation results show that the precision of tilting angle correction is 1.4%,
      suggesting that it is a feasible and effective correction method.

PMID- 19093563
TI  - [Study on intermolecular interaction between 4-aminopyridine and methacrylic acid
      using two dimensional FTIR spectroscopy].
AB  - A two-dimensional infrared (2D IR) correlation spectroscopy technique has been
      introduced to study the intermolecular interaction between 4-aminopyridine and
      methacrylic acid. The type and relationship of the bond between 4-aminopyridine
      and methacrylic acid molecule could not be characterized directly using the one
      dimensional FTIR spectroscopy. On the contrary, the interactions between 4
      aminopyridine and methacrylic acid molecule were determined using 2D IR
      correlation spectroscopy. The synchronous cross peaks exist between stretching
      vibrations of hydroxyl group of methacrylic acid at 1298 and 1202 cm(-1) and C=N
      group of 4-aminopyridine at 1531 cm(-1), and between carbonyl group of
      methacrylic acid at 1705 cm(-1) and N-H group of 4-aminopyridine at 3382 and 3212
      cm(-1), respectively. According to the two-dimensional correlation rules, the
      interactions of static electricity and hydrogen bonding exist between 4
      aminopyridine and methacrylic acid molecule. Such successful applications
      demonstrate that two-dimensional infrared correlation spectroscopy may be a
      convenient and effective means in the study of the intermolecular and
      intramolecular interaction.

PMID- 19093564
TI  - [Study on the method of FTIR spectrum non linear multiple point calibration].
AB  - FTIR Technique has developed rapidly since 1980s, and has become increasingly
      important. It has been used in a variety of fields. In order to make sure the
      result is of nicety, the authors should manipulate the FTIR spectrometer
      accurately and study its instrument response function and calibration arithmetic.
      Because the instrument response of the detector of FTIR spectrometer is different
      at different wave band, the no-calibrated spectrum was ruleless. Without
      calibration, we can not obtain the absolute intensity, even relative intensity.
      There are two calibration arithmetics: Linear calibration arithmetic
      corresponding linear detector and non-calibration arithmetic corresponding non
      linear detector. The present paper gave the arithmetic of linear calibration and
      non-linear multiple point calibration. The authors measured several blackbody
      spectra at some different temperatures. Some of them were used for calibration
      and one was used to test the result of calibration The result indicated that this
      method of non-linear multiple point calibration was very good. The relative
      arbitrary between calibrated blackbody spectrum and standard blackbody spectrum
      was near 0.2%, while the maximum was still lower than 0.4%.

PMID- 19093565
TI  - [A study of the diversity of different geographical populations of Emmenopterys
      henryi using FTIR based on principal component analysis and cluster analysis].
AB  - Emmenopterys henryi, an endemic species in China, has been one of the grade II
      national key conservation rare and endangered plants. The spectra of stem and
      leaf of Emmenopterys henryi sampling from seven different geographical
      populations were determined by Fourier transform infrared (FTIR) spectrometry
      with OMNI-sampler directly, fast and accurately. A positioning technology of
      OMNIC E.S.P.5.1 intelligent software and ATR correction was used. It was scanned
      for the background before the determination of every example. The peak value and
      absorbance were ascertained using a method of baseline correction in infrared
      spectra. Based on the indices of wave number-absorbance from 721 to 3366 cm(-1),
      the differences of these infrared spectra were compared by the methods of
      principal component analysis (PCA) and cluster analysis. Results showed that
      there were some differences in FTIR spectra between stem and leaf of Emmenopterys
      henryi, so it was better to study the diversity of different geographical
      populations through using the leaf, for which the distance coefficient of
      clustering analysis plot and the position relationship of principal component
      analysis three-dimensional plot of the seven populations were bigger. Being far
      away from others populations, the infrared spectra of Emmenopterys henryi in
      Dapan Mountain and Gutian mountain had special characteristics, indicating
      significant diversity. At the same time, the infrared spectra of Jiulong
      Mountain, Wuyan Mountain and Songyang populations had their own characteristics.
      There were no significant difference in the position relationship of three
      dimensional plot and distance coefficient of clustering analysis plot, showing
      that the chemical compositions of these three populations were of little
      difference, and the diversity differentiation was not remarkable. However, there
      were some significant differences in populations' diversity between Fengyang
      Mountain and Wencheng. It was indicated that the chemical composition of
      Emmenopterys henryi was affected by the special geographic positions and
      environment conditions. In a word, the remarkable differences in the chemical
      compositions of Emmenopterys henryi populations were consistent with their
      geographic distance far and near. The results also showed that there was good
      correspondence between the position relationship of PCA three-dimensional plot
      and distance coefficient of clustering analysis plot of the samples based on the
      indices of wave number-absorbance of FTIR and their geographic distance
      relationship. Therefore, FTIR can be used widely for studying and protecting the
      rare and endangered plants. It is not only provides the theoretic base of
      community ecology and ecosystem ecology of Emmenopterys henryi, but also has
      important theory and realistic meaning for exploring the mechanism of species
      endangerment, protecting and proliferating the populations of Emmenopterys
      henryi.

PMID- 19093566
TI  - [Research on shortwave NIR spectroscopy and its application to in situ flammable
      liquid detection].
AB  - Fast, accurate and highly effective detection in situ was important to the
      control of illegal transportation and the use of liquid state dangerous goods.
      The present article used the strong penetrability of the shortwave near-infrared
      ray to the packing material and liquid and measured the absorption spectra of
      some flammable liquids such as the absolute ethyl alcohol, absolute methanol,
      ammonia, turpentine, gasoline, diesel oil, petroleum etc and the partial liquors
      in the short wavelength region of NIR (667-1000 nm). The primitive spectral data
      were standardized and compressed, and then, the characteristic wavelength of the
      absorption spectra was analyzed using the SPSS statistics software. A math model
      for flammable liquid distinction was established based on the designated
      characteristic wavelength and can correctly detect flammable liquid using the
      absorbency of 3 wavelengths (881, 935 and 981 nm). According to the above the
      authors may construct the inexpensive spectrum instrument to check the flammable
      liquid non-destructively in situ.

PMID- 19093567
TI  - [Research on the sugar content measurement of grape and berries by using Vis/NIR
      spectroscopy technique].
AB  - Aiming at the nonlinear correlation characteristic of Vis/NIR spectra and the
      corresponding sugar content of grape and berries, the Vis/NIR spectra of grape
      and berries were obtained by diffusion reflectance. A mixed algorithm was
      presented to predict sugar content of grape and berries. The original spectral
      data were processed using partial least squares (PLS), and three best principal
      factors were selected based on the reliabilities. The scores of these 3 principal
      factors would be taken as the input of the three-layer back-propagation
      artificial neural network (BP-ANN). Trained with the samples in calibration
      collection, the BP-ANN predicted the samples in prediction collection. The values
      of decision coefficient (r2), the root mean squared error of prediction (RMSEP),
      and bias were used to estimate the mixed model. The observed results using PLS
      ANN (r2 = 0.908, RMSEP = 0.112 and Bias = 0.013) were better than those obtained
      by PLS (r2 = 0.863, RMSEP = 0.171, Bias = 0.024). The result indicted that the
      detection of internal quality of grape and berries such as sugar content by
      nondestructive determination method was very feasible and laid a solid foundation
      for setting up the sugar content forecasting model for grape and berries.

PMID- 19093568
TI  - [Near infrared determination of dry hay quality in oats].
AB  - In the present paper, the analysis of the content of CP, NDF and ADF in the whole
      dry hay of oats was carried out by using near infrared reflectance spectroscopy
      (NIRS) technique, and in combination with the partial least square (PLS)
      regression algorithm the calibration analysis was performed at the same time. The
      results showed that the calibration models developed by the spectral data
      pretreatment of the second derivative + Norris smoothing, the multivariate
      scattering correction + second derivative + Norris smoothing, and the
      multivariate scattering correction were the best for CP, NDF and ADF with the
      same spectral regions (9668-4518, 9550-5543, 8943-4042 cm(-1)). All these models
      yielded coefficients of determination of calibration (r2 cal) for CP and NDF that
      are both higher than 0.95, and each error lower than 3%, approached the chemical
      analysis precision. Moreover, the values of (RPD) of CP and NDF were both higher
      than 3.0. The results of these studies indicate that the contents of CP and NDF
      can be used to measure various samples in screening and evaluating quality
      constituents of dry hay in oats. While the effect of ADF modelling was poorer,
      the coefficients of determination of calibration (r2 cal) and cross validation
      (r2 CV)for ADF were 0.9120, 0.8553 respectively. The root mean square error of
      calibration, root mean square error of cross validation, and root mean square
      error of prediction ( RMSEE, RMSECV and RMSEP) for ADF were 2.33%, 2.62% and
      1.91% respectively, and the precision is near the precision of the chemical
      analysis. The models of ADF can be used to measure various samples in screening
      and evaluating quality constituents of dry hay of oats also. This study has
      proved that NIRS technique can be applied to detect the contents of CP, NDF and
      ADF in the whole dry hay of oats.

PMID- 19093569
TI  - [Discrimination of brownheart and watercore of apples based on energy spectrum of
      visible/near infrared transmittance].
AB  - It is urgent to develop a quick and precise method for the discrimination of the
      internal quality of apple. Vis/NIR spectroscopy combined with multivariate
      analysis after the appropriate spectral data pre-treatment has been proved to be
      a very powerful tool for judgment of objects that have very similar exterior
      properties. In the present study, peak area discriminant analysis (PADA),
      principal component analysis discriminant analysis (PCADA) and partial least
      squares discriminant analysis (PLSDA) were applied to classify apples with
      different internal properties such as brownherat and watercore. Energy spectra
      were processed using MSC or one-order derivative, and three models using PADA,
      PCADA and PLSDA were built, respectively. The accuracy rates of prediction for
      brownheart apple were 100%, for watercore apple were 79.6%, 95.0% and 96.7%, and
      for natural apple were 88.4%, 98.2% and 98.8%, respectively. The PLSDA model was
      better than the others remarkably. And the overall correct ratio of PLSDA was
      98.1%, with RMSEC = 0.449 and RMSEP = 0.392. The results in the present study
      show that Vis/NIR spectroscopy together with chemometrics techniques could be
      used to differentiate brownheart and watercore apple, which offers the benefit of
      avoiding time-consuming, costly and sensory analysis.

PMID- 19093570
TI  - [Raman spectra studies of MBE-grown n-GaAs/SI-GaAs films].
AB  - n-GaAs films doped with Si were grown by MBE on semi-insulated GaAs (100)
      substrates. The films with different doping concents were characterized by Raman
      spectra at room temperature. It is obviously that the Raman peaks shifted. Some
      peaks were enhanced and some were weakened. This is attributed to the fact that
      the higher the doping contents, the highertge lattice mismatch. And the lattice
      misfit induced the imperfection in epitaxy layers. This experimental result
      coincides with the theory.

PMID- 19093571
TI  - [A primary Raman microscopic study of the turquoise and its role in provenance
      tracking].
AB  - The authors analyzed four modern turquoises from Hubei province and Anhui
      province by using the Raman microscopic with the samples are gathered on the
      spot. According to the study the authors discovered that the Raman spectra of the
      Hubei turquoises with different color but with the same backgrounds of mineral
      resource and the formation cause of mineral resource and in the same formation
      line of turquoise mineral resource have little difference. On the contrary, there
      is a strong difference in the 900-100 cm(-1) region of the Raman spectra between
      the turquoises from Hubei province and the turquoise from Anhui province which
      has remarkable different backgrounds of mineral resource and the formation cause
      of mineral resource. At the same time the authors studied two ancient turquoises
      to discuss the feasibility of using the Raman spectra of turquoises, the
      provenance of which is known, as the fingerprint directions to track the
      provenance of ancient turquoises.

PMID- 19093572
TI  - [Study on vibrational spectra of ethyl hexanoate molecule].
AB  - The vibrational spectra of ethyl hexanoate were calculated by the density
      functional theory (DFT) with B3LYP complex function, diffuse function and
      polarization function added to heavy atoms and light atoms. On the base of this,
      the normal Raman spectrum (NRS) and the infrared spectrum (IR) were assigned in
      detail in the present paper. Comparing the calculated results with the
      experimental data, the calculated results are in good agreement with the
      experimental results. The comparison of the experimental Raman and infrared
      spectra shows that in the experimental Raman spectrum, the strongest bands appear
      at the frequencies of 2600-3100 cm(-1), while the strongest band is not 1734 cm(
      1) but 1444 cm(-1) at the frequencies of 400-2000 cm(-1). The band 1734 cm(-1)
      attributed to the C=O stretch vibration is the distinctive mark of organic ester
      compounds, and the band 1444 cm(-1) is related to the symmetric and anti
      symmetric scissors vibration of C-H. In the experimental infrared spectrum, the
      strongest vibrational band is 1739 cm(-1), which is related to C=O stretch
      vibration; At the frequencies of 400-2000 cm(-1), the relative intensity of the
      infrared spectrum is distinctively stronger than that of the Raman spectrum, but
      the relative intensity of infrared spectrum is weaker than that of the Raman
      spectrum at the frequencies of 2600-3100 cm(-1). In the frequencies of 2600-2800
      cm(-1), the vibrational bands 2762 and 2732 cm(-1) do not appear in the
      experimental spectra, which may originate from two reasons: (1) the weak
      interaction of molecules. Also, the relative intensity of these vibrational bands
      is very weak in the experimental spectra, and this may testify that the
      interaction of molecules is rather weak; (2) the vibrational bands may belong to
      second order vibrational mode at the frequencies of 2600-2800 cm(-1). The
      relative intensity of infrared bands is weaker than that of the Raman bands at
      the frequencies of 2600-2800 cm(-1). At the end, the stronger bands appearing in
      Raman and infrared experimental spectra are assigned as characteristic marks,
      respectively. The study on vibrational spectra of ethyl hexanoate molecule may
      have great application value in detection of liquor flavor, chemical industry and
      biology fields, providing important reference value for the related basic
      research field.

PMID- 19093573
TI  - [Investigation on composites of europium fluorescent complexes and
      polyvinylpyrrolidone].
AB  - In order to investigate the relationship between the aggregation structure and
      fluorescence properties of composites of rare earth fluorescent complexes and
      polymers, the fluorescent complexes of Eu(TTA)3 x 2H2O and Eu(TTA)3 x (TPPO)2
      were synthesized by the reaction of TTA (2-thenoyltrifluoroacetone), TPPO
      (triphenylphosphine oxide) and EuCl3, and their composites with
      polyvinylpyrrolidone (PVP K30) were prepared. The fluorescence spectroscopy, FTIR
      spectroscopy and TEM were used to characterize these composites. Fluorescence
      spectroscopy results indicated that the fluorescence intensity of the
      PVP/Eu(TTA)3 x 2H2O composites is obviously improved compared with that of the
      Eu(TTA)3 x 2H2O complexes. For the composites with the molar ratio of the
      complexes to the repeat unit of PVP being 1:35, the intensity of 612 nm emission
      peak of the composites is 5.5 times for PVP/Eu(TTA)3 x 2H2O and 0.3 times for
      PVP/Eu(TTA)3 x (TPPO)2 higher than that of the corresponding pure rare earth
      fluorescent complexes. And the emission intensity ratio of 612 to 590 nm peak is
      14.7 in PVP/Eu (TTA)3 x 2H2O composite, larger than that of Eu(TTA)3 x 2H2O
      complexes. These results suggested that the luminescent properties of the
      europium fluorescent complexes were obviously enhanced in the presence of PVP
      matrix and there are interactions between the fluorescence complexes and PVP
      molecules. In the presence of PVPK30, the FTIR spectra of the Eu(TTA)3 x 2H2O
      complexes were obviously influenced as well. Based on the curve-fitting results
      of IR spectra of PVP/Eu(TTA)3 2H2O composites with the molar ratio of repeat unit
      of PVP to Eu(TTA)3 x 2H2O being 7:1 and 2:1, multiple absorption peaks of nu C=O
      are observed. The IR spectral variations indicated that there are coordination
      interactions between Eu3+ ions and the carbonyl groups of PVP, and multiple
      coordination fashion exists. TEM results showed that there are microphase
      separation structures in PVP/Eu(TTA)3 x 2H2O and PVP/Eu(TTA)3 x (TPPO)2
      composites. The microphase separation phenomenon in composite of PVP/Eu(TTA)3 x
      (TPPO)2 is more obvious than that of the PVP/Eu(TTA)3 x 2H2O. And the Europium
      complexes are in amorphous state, which further proved the interactions between
      PVP molecules and the rare earth fluorescence complexes Eu(TTA)3 x 2H2O and
      Eu(TTA)3 x (TPPO)2.

PMID- 19093574
TI  - [Spectral analyses during the isolation course of Spirulina platensis
      phycobilisomes using low-speed centrifugation].
AB  - The phycobilisomes were isolated from Spirulina platensis using low-speed
      centrifugation. The crude phycobilisomes solution extracted by Triton X-100 was
      centrifugated (13000 rpm) four times. The centrifugated phycobilisomes solution
      was spectrally analyzed using absorption spectrum each time. The absorption
      spectrum showed that the ultraviolet absorption maximum of the phycobilisomes
      solution was still at 263 nm, and also exhibited the characteristic
      chlorophyllous absorption in the rang of 400-450 nm after the fourth
      centrifugation. This indicated that there existed small quantities of Triton X
      100 and chlorophyll in the centrifugated phycobilisomes solution. But the
      ultraviolet absorption maximum was red-shifted to 277 nm and the chlorophyllous
      absorption was not observed in the absorption spectrum of the phycobilisomes
      solution obtained by high concentration salt precipitation, which meant that the
      method of high concentration salt precipitation could effectively remove Triton X
      100 and chlorophyll from the phycobilisomes solution. The precipitated
      phycobilisomes of Spirulina platensis were further purified by using Sepharose CL
      6B column chromatography. The fluorescence emission maximum of the purified
      phycobilisomes at room temperature was at 680 nm, which indicated that the
      purified phycobilisomes were intact.

PMID- 19093575
TI  - [Study of the interaction of atrazine and ct-DNA by fluorescence probe
      technique].
AB  - The interaction atrazine and ct-DNA was studied using fluorescence probe and UV
      absorption spectroscopy technique. Ethidium bromide (EB) was used as a probe. The
      effects of atrazine, phosphate, concentration of ions, and potassium iodide on
      the fluorescence of ct-DNA-EB system were investigated. The results showed that
      the fluorescence quenching process of atrazine to ct-DNA-EB system was proved to
      be the simultaneous dynamic and static quenching model. The phenomena of
      fluorescence quenching of ct-DNA-atrazine system by KI and hyperchromicity and
      the red shift of DNA UV-absorption caused by atrazine indicated the existence of
      intercalation between atrazine and ct-DNA. The experiments of phosphate and ionic
      strength showed that atrazine could combine with the phosphate group of ct-DNA by
      non-characteristic static force, and this action could be inhibited by high ionic
      strength.

PMID- 19093576
TI  - [Preparation and spectroscopic studies of nanosilver/silk-fibroin composite].
AB  - The development of reliable, eco-friendly processes for the synthesis of
      nanomaterials is an important aspect of nanotechnology today. One approach that
      shows immense potential is based on the in situ synthesis of noble metal
      nanocolloids using natural biological material such as silk fibroin. In the
      present paper, the nano-Ag/silk-fibroin colloids were prepared by in situ
      reducing AgNO3 with silk-fibroin at room temperature without any reducing agent.
      UV-Vis absorption, atomic force microscopy, fluorescence spectra and resonance
      scattering spectra were used to study the preparation process and
      characterization of the nanocomposite. It was found that the formative Ag
      nanoparticles were attributed to the tyrosine residues in the chains of silk
      fibroin that act as reduction agent in the reduction course of AgNO3, and the Ag
      nanoparticles were uniformly embedded in silk-fibroin colloid, which possess good
      dispersity and stability and can be kept for a long period. The strength of
      fluorescence spectra increased after reaction of silk-fibroin with AgNO3
      solution, showing that there was a strong chemical adsorption between silver
      nanoparticles and silk-fibroin, and a stable complex layer was formed in silver
      nanoparticles. Meanwhile the existence of silver nanoparticles in silk-fibroin
      was proved by resonance scattering spectra.

PMID- 19093577
TI  - [Preparation and spectrum of multilayer films of polyoxometalate
      {(Eu(PW11)2)m/PEI}].
AB  - The layer-by-layer assembly (LBL) is a new method of thin film deposition often
      used for oppositely charged polyelectrolytes. LBL technique has been extensively
      used to make multilayer films of polyions with biomolecules such as proteins,
      enzymes and DNA. It can also be successfully applied to the preparation of thin
      films of nanoparticles. Ultrathin multilayer films containing a polyoxometalate
      (Eu(PW11)2)m and PEI were prepared using layer-by-layer assembly method in the
      present work. The stable multilayer films were assembled by alternate adsorption
      of negatively charged POM and positively charged polyelectrolytes from their
      aqueous dispersions. The growth of the multilayer films is regular. The proposed
      novel immobilized method exhibited good stability and the photoluminescent
      behavior of films at room temperature was investigated to show the Eu3+
      characteristic emission pattern, which is important for practical application.

PMID- 19093578
TI  - [Study on the fluorescence characteristics of BOD sensing films immobilizing
      different limnetic microorganism].
AB  - Taking tetramethoxysilane (TMOS) and dimethyldimethoxysilane (DiMe-DMOS) as
      precursors for the synthesis of an organically-modified silicates (ORMOSILs),
      optical BOD sensing films immobilizing five kinds of limnetic microorganisms were
      composed by poly(vinyl alcohol) ormosils matrix. Their fluorescence
      characteristics were studied with a home-made optical BOD apparatus. According to
      the experimental results, linearity between BOD and the corresponding
      fluorescence intensity ranging from 0-60 mg x L(-1) to 0-120 mg x L(-1) could be
      obtained on the sensing films immobilizing limnetic microorganisms and their
      mixture. In addition, the linearity coefficient was from 0.976 to 0.997, and the
      respond time was 0.5 to 8.7 min. In the experiment, effects of the measurement
      condition such as temperature and pH on the fluorescent responses of BOD sensing
      films were investigated. These sensing films presented excellent reproducibility
      and stability since they could be continuously employed for 30 days, and kept 85%
      of their original activity when stored for 12 months at 4 degrees C. The approved
      approach could be applied in the BOD determination of real limnetic samples
      according to the obtained results.

PMID- 19093579
TI  - [Studies on the action features between cefuroxime axetil and bovine serum
      albumin].
AB  - Under different temperatures and physiological conditions, with cefuroxime axetil
      concentrations in the range of 1.959 X 10(-6) to 13.71 X 10(-6) mol x L(-1), and
      bovine serum albumin (BSA) concentrations at 2.0 X 10(-6) mol x L(-1), the
      interaction between cefuroxime axetil and BSA was studied by fluorescence
      spectroscopy, three-dimensional fluorescence spectrum, synchronous fluorescence
      spectrum and UV-Vis absorption spectroscopy. After analyzing and processing the
      fluorescence quenching data at different temperatures according to Sterm-Volmer
      equation, Lineweaver-Burk equation and thermodynamic equation, the average value
      of the apparent binding constant (K(LB): 3.907 X 10(6) L x mol(-1)), and
      thermodynamics parameters (enthalpy change delta H: -13.43 kJ x mol(-1), entropy
      change delta S: 81.90 J x K(-1) and standard Gibbs free energy change delta G0: 
      38.34 kJ x mol(-1)) were calculated, and the amounts of binding sites (n:
      1.042)were measured. The fluorescence quenching mechanism of BSA after cefuroxime
      axetil was added was discussed. BSA was bound with cefuroxime axetil and formed a
      new compound. The quenching belonged to static fluorescence quenching. The
      thermodynamic parameters agree with delta H approximately 0, delta S > 0 and
      delta G0 < 0, and the binding reaction is mainly entropy-driven and electro
      static interaction force plays a major role in the reaction. The maximum emission
      wavelength of Tyr and Trp had an obvious red shift in the synchronous
      fluorescence spectra, the fluorescence emission wavelength of two peaks had a
      blue shift in the three-dimensional fluorescence spectrum of BSA in the presence
      of cefuroxime axetil and the maximum absorbtion wavelenghs of three systems in
      the UV-Vis absorption spectra were obviously different. These showed that the
      changes in the micro-environment of Tyr and Trp and demonstrated that the
      conformation of BSA changed as cefuroxime axetil had been added. This provides
      important information for discussing the configuration modification of BSA
      because of the added cefuroxime axetil, and for elucidating the pharmacological
      effects of cefuroxime axetil and biological effects in the organism.

PMID- 19093580
TI  - [Study on styrene derivatives with stilbene-like pendant: synthesis and the
      fluorescence properties].
AB  - A series of styrene derivatives with stilbene-like pendant were synthesized
      through heterogeneous Wittig reaction of triphenyl-(4-vinyl)-benzylphosphornium
      chloride with aromatic aldehydes. The substituted styrenic monomer, 4-(2-aryl)
      vinyl-styrene, was strongly photoluminescent in solution and in solid state.
      Introduced electron-pushing substituents and lengthened conjugation both enhanced
      the emission intensity and led to a red shift of emission bands, with the maximum
      emission wavelength shifted from 378 to 494 nm. The fluorescece quantum
      efficiencies were determined by employing quinine sulfate as reference; and 4-(2
      anthryl)-vinyl-styrene (AVS) possessed the highest quantum efficiency (lambda =
      494 nm, phi(f) = 0.635).

PMID- 19093581
TI  - [Study on the interaction between p-HPcZn and myoglobin].
AB  - The interaction of p-HPcZn and myoglobin was studied by fluorescence spectra and
      synchronous fluorescence spectra methods under the physiological condition. The p
      HPcZn can quench the fluorescence of myoglobin effectively, and it is indicated
      that there is a strong interaction occurring between p-HPcZn and myoglobin. The
      results of the fluorescence spectra with changing temperature proved that the
      interaction can lead to the formation of complex of p-HPcZn with myoglobin, and
      quench the fluorescence of myoglobin through the static quenching mechanism.
      Dealing with the values of fluorescence spectra, the binding parameter and the
      binding site of the interaction can be obtained, whose values are 2.481 X 10(5)
      and 0.444 respectively. In addition, the interaction can change the conformation
      of myoglobin markedly also.

PMID- 19093582
TI  - [Resonance scattering spectral properties of CdTe nanoparticles and its
      application].
AB  - In the present paper, CdTe quantum dots were prepared, and the resonance
      scattering, fluorescence and absorption spectral properties of CdTe quantum dots
      in aqueous solution were studied in details. The fluorescence spectral results
      showed that the CdTe quantum dots of 3.8, 4.0 and 4.6 nm in diameter have
      fluorescence peaks at 601, 625 and 654 nm, respectively, the fluorescence peak
      (lambda F) red shifts, and the fluorescence intensity is proportional to the CdTe
      concentration. The linear relationship was found between the fluorescence peak
      wavelength and the logarithm of the diameter. The relationships was lambda F =
      126.74 ln(d) + 395.92, with a related coefficient of 0.9945. For CdTe quantum
      dots of 3.8 nm in size, the fluorescence intensity at 601 nm was proportional to
      the concentration in the range of 11.25-540 micromol x L(-1). The regression
      equation is F601 nm = 0.7223c + 3.28, with a correlation coefficient of 0.9980.
      The absorption spectral results showed that the CdTe quantum dots of 3.8, 4.0 and
      4.6 nm in diameter have absorption peak at 550, 573 and 590 nm, respectively. The
      absorption value is proportional to CdTe quantum dots concentration. For CdTe
      quantum dots of 3.8 nm in size, the concentration in the range of 11.25-180.0
      micromol x L(-1) obeys Lamb-Beer's law. The absorption peak (lambda A) also red
      shifted and widened, absorption value decreased with the diameter (d). The linear
      relationship was found between the absorption peak wavelength and the logarithm
      of the diameter. The relationships was lambda A = 155.01 ln(d) + 415.52, with a
      related coefficient of 0.9956. The resonance scattering (RS) spectra showed that
      the CdTe quantum dots of 3.8, 4.0, 4.6, 4.8, 5.2, 6.5 and 8.6 nm in diameter have
      resonance scattering peaks at 597.94, 622.02, 645.94, 654.05, 656.95, 700.98, 735
      nm respectively. The RS peak wavelength lambda R is also proportional to the
      logarithm of the diameter of CdTe quantum dots. Its regression equation is lambda
      R = 148.37 ln(d) + 418.08 and the correlation coefficient is 0.9952. For CdTe
      quantum dots with the same diameter such as 3.8 nm, the resonance scattering
      intensity at 597 nm is proportional to the CdTe concentration. The linear range
      is 22.5-180.0 micromol x L(-1), the regression equation is I597 nm = 0.5721c +
      5.884, and the correlation coefficient is 0.9975. A new resonance scattering
      method was applied to the determination of the diameter of CdTe quantum dots,
      with the advantages of simplicity, quick operation and good practical values.

PMID- 19093583
TI  - [Estimating the severity of rice brown spot disease based on principal component
      analysis and radial basis function neural network].
AB  - An ASD Field Spec Pro Full Range spectrometer was used here to acquire the
      spectral reflectance of healthy and disease leaves cut from rice plants in the
      field. The leaf disease severity of rice brown spot was determined by estimating
      the percentage of infected surface area of rice leaves in the laboratory through
      phytopathologist's observation. Three steps were taken to estimate leaf disease
      severity of rice brown spot. The first step was that different spectra
      transforming methods, namely, resampling spectrum (10 nm interval), the first-
      and second-order derivative spectrum based on raw hyperspectral reflectance, were
      conducted. The second step was that the principal component analysis (PCA) was
      examined to obtain the principal components (PCs) from the above transformed
      spectra to reduce the spectra dimensions of hyperspectral reflectance and
      simplify the data structure of hyperspectra. The last step was that the
      resampling and PCs spectra entered the Radial Basis Function neural network
      (RBFN) as the input vectors, and the disease severity of rice brown spot entered
      RBFN as the target vectors. RBFN is an effective feed forward propagation neural
      network, which is based on the linear combinations of corresponding radial basis
      functions. In general RBFN can be used to solve the problems such as regression
      or classification with high operation rate and efficient extrapolation
      capability, and quickly designed with zero error to approximate functions. The
      total dataset (n = 262) was divided into two subsets, in which three quarters (n
      = 210) was the training subset to train the neural network, and the remaining
      quarter (n = 52) was the testing dataset to conduct the performance analysis of
      neural network. The spread constants of RBFN and various data processing methods
      were investigated in detail. The best prediction result was obtained by PCs
      spectra based on the first-order derivative using RBFN model, the root mean
      square of prediction error (RMSE) was small (7.73%) in the testing dataset, and
      the next was the resampling spectra with RMSE of 8.75%. This research
      demonstrated that it was feasible and reliable to estimate the disease severity
      of rice brown spot based on PCA-RBFN and hyperspectral reflectance at the leaf
      level.

PMID- 19093584
TI  - [Determination of nutrients in 7 species of desert plants for raising livestock
      in inner Mongolia].
AB  - In order to accumulate the foundational information about the nutrients related
      to 7 species of desert plants, chemical and instrumental methods for
      determination were used and quantitative results were obtained as follows (%, in
      dry mass): calcium 0.73-3.89, phosphorus 0.043-0.34, selenium 0.026-2.8, protein
      3.38-13.92, lipid 3.97-15.03, total sugar 14.89-35.78, ash 0.61-14.33, medium
      washing fiber 26.66-79.72, and acid washing fiber 27.03-69.01. Among the 7
      species of desert plants, the total content of amino acid in the leaf and caudex
      ranges from 2.30% to 11.26%. Apart from Elaeagnus angusti folia, the ratios of
      the calcium and phosphorus both in the leaves and caudexes of the rest 6 kinds of
      desert plants are higher than those in the leaf powder and caudex powder of
      clover blossom. The selenium content is greater than the usual amount in plants;
      the protein content reaches the level of excellent grains; the lipid contents in
      leaf, caudex and whole plant are higher than those in straws of corn and wheat;
      the leaves have more total sugar than the caudex and the whole plant, and the
      high level of ash content exists in the 7 species of desert plants; and the
      medium washing fiber content in leaf of those plants is lower than that in clover
      blossom leaf powder, which is opposite to the content in caudex. Except for
      Haloxylon ammodendron, the acid washing fiber content in caudexes is beyond that
      in the caudex powder of the clover blossom. As is indicated in the data above,
      the 7 species of desert plants not only do meet the demands of raising livestock,
      but also are ideal feeding resources for the husbandry development in sandy
      areas.

PMID- 19093585
TI  - [Study on fluorescent properties of coumarin derivatives and determination of
      trace iron].
AB  - The fluorescence spectra of the succinic acid (7-hydroxy-coumarin) ester (SCE) of
      different concentration in water and ethanol solvents were studied. It was found
      that the peak wavelength changes not only with solvent, but also with the
      concentration. These phenomena of spectra have been discussed on the basis of
      solvent properties and dimerisation of SCE in hydrogen bonding solvents. The
      author thought that there are dimerisation phenomena in the SCE solutions at high
      concentration. The formation of dimer was caused by the aid of hydrogen bonding
      between SCE and solvent or between SCE themselves. Its acidic dissociation
      constant at excited state was determined based on the changes of the fluorescence
      spectra in water. And a simple and sensitive fluorescence quenching method for
      the determination of trace iron was developed. The method is based on the
      reaction of SCE with iron in hydrochloric acid medium. The fluorescence intensity
      was measured with excitation and emission wavelengths of 347 and 457 nm,
      respectively. The linear range for the determination of iron was 0.66-6.59 microg
      x L(-1). The detection limit was 51 ng x L(-1). The author contrasted SCE with 7
      hydroxy-coumarin to determine Fe3+, and found the sensitivity of SCE is 10(4)
      higher than that of 7-hydroxy-coumarin. To our thinking there is a carboylate
      group in SCE, whose coordinate force with iron is stronger than hydroxide radical
      in 7-hydroxy-coumarin.

PMID- 19093587
TI  - [Determination of se in blood and tissue of animal samples by normal ICP-MS and
      ICP-MS with octupole reaction system].
AB  - The Se in the blood and tissue of animal samples was determined by ICP-MS
      instrument. The method was not only proved simple and rapid, but also showed
      satisfying precision and low detection limit. The optimum conditions of ICP-MS
      for the method were investigated. Results by the digestion method, the isotopes
      selection, and the difference between the normal ICP-MS without ORS (Octopole
      Reaction System) and the ICP-MS with ORS were compared, which afford reference to
      the determination of the same kinds of sample. The standard materials were
      determined to proved the reliability of the normal ICP-MS and the ORS-ICP-MS
      methods. The ORS-ICP-MS can effectively remove the interference based on
      polyatomic ions, so the the detection limits were lowed, and the accuracy was
      improved. The detection limits of the method for normal ICP-MS is 0.024 ng x g(
      1) and that for ORS-ICP-MS is 0.004 6 ng x g(-1), the RSDs are between 1.8% and
      5.5%, and the recoveries of the method are in the range of 90.8%-107.2%.

PMID- 19093586
TI  - [Catalytic spectrophotometric quantitation for hypoxanthine by conjugating
      xanthine oxidase with horseradish peroxidase].
AB  - A novel technology to determine the concentration of hypoxanthine through the
      chromogenic reaction of phenic acid (PA), 4-aminoantipyrine (AAP) and hydrogen
      peroxide (H2O2), which was produced via the oxidation of hypoxanthine catalyzed
      by xanthine oxidase (XO), under the help of horseradish peroxidase (HRP) was
      proposed in the present paper, according to the reaction of molybdoenzyme
      xanthine oxidase (XOD, EC 1.2.3.22) which mainly catalyzes the conversion of
      hypoxanthine and xanthine to xanthine and uric acid, respectively, and is capable
      of reducing oxygen to generate the reactive oxygen species (ROS), superoxide and
      hydrogen peroxide. The influences of temperature and pH on the system were
      investigated. The optimal conditions to determine the concentration of
      hypoxanthine were obtained as follows: XO (0.32 U x mL(-1)), HRP (7.0 U x mL(
      1)), 4-Aminoantipyrine (1 mmol x L(-1)), and phenic acid (6 mmol x L(-1)) were
      dissolved in 100 mmol x L(-1) Tris-HCl buffer solution (pH 8.3), and the reaction
      system was incubated in thermostat of 37 degrees C for 8 min, the absorptive wave
      length was 508 nm. Under the conditions mentioned above, the linear range of
      calibration curve was between 0.2 and 3.0 mmol x L(-1), the correlation
      coefficient was 0.9979, and the limit of detection was 0.05 mmol x L(-1). All
      these show that this technology is a potential alternative method to determine
      the concentration of hypoxanthine in areas like for example in laboratory or
      clinical serum diagnosis.

PMID- 19093588
TI  - [Determination of trace elements in different parts of grapefruit by ICP-AES].
AB  - In the present paper, a method of simultaneous determination of trace elements in
      grapefruit was developed by using inductively coupled plasma-atomic emission
      spectrometry together with HNO3-HClO4 digestion. The contents of fifteen
      elements, including B, Ba, Ca, Cu, Zn, Mg, Sr, Mn, Fe, Na, Be, Pb, Bi, Cd and As,
      were determined in four parts, namely flesh, scarfskin, endodermis and seed
      collected from Guangdong, Guangxi and Ganzhou, respectively. The relative
      standard deviations for all these elements in this method were between 0.22% and
      5.54%, and the recovery rates were between 87.0% and 115.0%. The measuring method
      was proved to be simple, rapid, reliable, and highly sensitive. In addition, the
      determination of these fifteen elements can be carried out at the same time,
      which can meet the requests of actual sample analysis. The experimental results
      showed that some beneficial elements to human such as Ca, Mg, Fe, Zn, Mn, Cu and
      Na in grapefruit were abundant, while some comparatively harmful elements (Be,
      Pb, Bi, Cd and As) were not detected. Regional differences and partial
      differences obviously existed in the concentrations of one or more trace elements
      in grapefruit. As a whole, the concentrations of most elements in flesh were much
      lower than in other parts of grapefruit. The concentrations of B, Ba, Ca, Sr and
      Mn were comparatively higher in the seed capsule than in other parts. Cu, Zn and
      Mg had the highest concentrations in seed compared to other parts. There was
      little difference between scarfskin and endodermis. And as for the regional
      differences, the contents of Mn, Zn and Na in Gannan pomelo in all its parts were
      higher than those in other regions, and the contents of Ba in Guangdong pomelo in
      all its parts were higher than those in others, while Guangxi pomelo had the
      highest Fe content. These differences might resulted from the natural
      environmental conditions such as temperature, humidity, soil types with different
      pH, the mineral composition or concentration, and so on. Application of
      fertilizer and prunning might be an important man-made factors which could also
      result in the differences. The determination of these elements by using ICP-AES
      has important point for exploiting grapefruit fully in future.

PMID- 19093589
TI  - [Determination of inorganic elements in rat serum, and vegetable and fruit
      ferment liquid by ICP-MS].
AB  - In the present paper, the contents of thirteen inorganic elements in rat serum,
      and vegetable and fruit ferment liquid (VFFL) were measured by ICP-MS in order to
      study the anti-tumor effect of VFFL. Serum or VFFL was digested in nitric and
      perchloric acids at room temperature and then heated until dryness. The residue
      was dissolved with 1% (phi) nitric acid prior to ICP-MS analysis. The element
      contents were quantitated by using 45Sc, 103Rh and 187Re as the internal
      standards, respectively, according to the rule of close mass number. Certificate
      references bovine serum (GBW(E)090006) and tea (GBW070605) were employed to
      validate the proposed method, and the analysis results of most elements in two
      certificate references were in agreement with their reference values. The intra
      day and inter-day precisions of the method in terms of relative standard
      deviation (RSD) were mainly below 10% and below 15%, respectively. The spiked
      recoveries for most of studied elements were 80%-110% in rat serum and 90%-120%
      in VFFL. This method was rapid, highly sensitive, and especially suitable to
      being applied to small quantity of biological samples with greatly different
      elements contents. Therefore, we measured the content of thirteen elements in the
      sera of rats, where in were induced liver cancer by revulsant, and the rate were
      fed with different dosage of VFFL in intragastric infusion at the same time. It
      was preliminarily found that the concentrations of some elements in sera of
      different experiment groups of rats were significantly different, implying the
      potential anti-tumor effects of VFFL.

PMID- 19093590
TI  - [Effects of hair dyeing on the heavy metals content in hair].
AB  - Cosmetic and hair dye has been one of the pollution resources of heavy metals.
      Contents of heavy metals in hair of dyed group and non-dyed group were analyzed
      by ICP-MS, the results showed that dyeing hair can change the content of heavy
      metals in hair, but the degree of effect is different for different element:
      contents of Mn, Fe, Ni, Cu, Cd and Sb in hair of dyed group were higher than that
      of non-dyed group, but contents of As, Cr, Zn, Ag, Pb and Hg were lower. The
      cause of the above results could be that hair dye contains more Mn, Fe, Ni, Cu,
      Cd and Sb, but less As, Cr, Zn, Ag, Pb and Hg, and dyeing hair could restrain the
      metabolism and excretion of As, Cr, Zn, Ag, Pb and Hg from human body.

PMID- 19093591
TI  - [Determination of trace mercury in hair by hydride generation atomic fluorescence
      spectrometry].
AB  - A method for determination of trace mercury in hair by hydride generation atomic
      fluorescence spectrometry under normal or high temperature and high humidity
      condition was described. The ways of samples pretreatment, analysis and rapid
      clearing up bad memory were researched. The results showed: that the effect of
      instability of mercury can be cushioned under high temperature and high humidity
      condition by choosing much negative high pressure and control long the
      fluorescence intensity of standard blank. There weren't evident differences in
      the measure results of standard graph, standard and sample between normal and
      high temperature and high humidity conditions. When the reducer concentration was
      more than 2.5 percent or less than 1.5 percent the fluorescence signal was often
      overrun or disappeared. The sensitivity and stability of instrument weren't
      easily balanced. Due to sulfuric acid remainder, the fluorescence intensity of
      sample blank was higher than that of standard blank, especially under high
      temperature and high humidity, so in the proceed of sample pretreatment sulfuric
      acid was used scarcely. The bad memory effect can be cleared up rapidly by
      correction of negative high pressure and correction of of timized standard graph.
      The method was rapid and accurate. The relative standard deviation (RSD) was
      equal to or small than 1.1%. The detection limit of the method was 0.006 ng x mL(
      1).

PMID- 19093592
TI  - [Comparison and correlative analysis of trace elements in five kinds of radix
      curcumae].
AB  - Traditional Chinese medicine materials (TCM) contained abundant trace elements
      needed in human body. Mixed acid (HNO3:HClO4) was added into samples treated by
      microwave digestion, and a systematic study was carried out by selection of the
      most appropriate working conditions and optimization of the sample mass. Some
      inorganic elements in 5 kinds of radix curcumae (Curcuma wenyujin Y. H. Chen et
      C. Ling, Curcuma longa L., Curcuma kwangsiensis S. G. Lee et C. F. Liang, Curcuma
      phaeocaulis Val. and Curcuma chuanyujin C. K Hsieh et H. Zhang) necessary to
      lives were determined by flames atomic absorption spectrometry (AAS). Elements,
      such as K, Ca, Na, Mg, Zn, Fe, Cu and Mn were detected. The results show that
      there are similar elements in the five kinds of radix curcumae, while differences
      only exist in a few elements contents. The correlative analysis of trace elements
      in samples was carried out by cluster analysis of the 4 kinds of radix curcumae
      (Curcuma wenyujin Y. H. Chen et C. Ling, Curcuma longa L., Curcuma kwangsiensis
      S. G. Lee et C. F. Liang and Curcuma phaeocaulis Val. ) in codex populations in a
      cluster, different from the unofficial sample (Curcuma chuanyujin C. K. Hsieh et
      H. Zhang). The cluster analysis results are consistent with the morphological
      characteristics of the traditional taxonomy results. The results showed that the
      analytic method is advisable. This paper provides scientific basis for deeply
      studing the relation between trace elements and drug effect of radix curcumae.

PMID- 19093593
TI  - [XPS analysis of tea plant leaf and root surface].
AB  - XPS was applied to analyze the surface chemical composition and structure of the
      tea plant leaf and root. It was detected that the surface is made up of mainly 4
      elements: C, O, N and Al, with little P and F in abaxial leaf. Based on the
      botanic epidermis structure and the chemical composition, with the help of the
      standard spectrum data bank on line and the wood XPS study results, and through
      line Gaussian and Lorentizian the mixed, the binding energy of C(1s) of the leaf
      surface was classified as 3 types: the first was C1, with the electron binding
      energy of 285 eV, from C-C or C-H group, representing lipid compound like cutin
      and wax. C2 with the binding energy of 286.35 eV in the adaxial and 286.61 eV in
      the abaxial, came from the single bond of carbon and oxygen C-O, mainly standing
      for cellulose. C3 with the binding energy of approximately 288 eV (288.04 eV in
      adaxial and 288.09 eV in abaxial) was the sign of C=O group, which is acyl in
      protein with the confirmation of N(1s) (399-401 eV)and O(1s) analyses. In the
      root surface, besides the same compounds of cutin and wax (C1, binding energy 285
      eV), cellulose (C2, binding energy 286.49 eV) and protein (C3, binding energy
      288.78 eV)as in the leaf, there appeared C5 type with the binding energy of
      283.32 eV. Because it was lower than C1, it was estimated as carbon linking to
      metal. Both the leaf and the root surfaces didn't have C4, a type of O-C=O, which
      is common in wood surface with the highest oxidated carbon of 289-289.5 eV
      binding energy, indicating that organic acid secreted by the root existed freely
      on the root surface, without any chemical association with the surface compounds.
      The results of the separated spectrum of O(1s) supported the above C(1s) results.
      By the ratio of each type of C, there were more oxygen groups in the abaxial than
      in the adaxial, implicating more active chemical properties on the abaxial.
      Compared with the leaf, cutin and wax was little in the root and oxygen groups
      were many, verifying more active chemical property on the root surface and more
      water and solute molecules passing. Again the protein content was in the order of
      root, abaxial and adaxial, indicating the same order of the wetness degree.
      Higher binding energy of Al than 73. 50 eV showed oxidized aluminum in tea plant
      surface, which might enhance the absorption, and more oxidized aluminum in the
      root meants that it has more powerful absorbability.

PMID- 19093594
TI  - [Study of malignant and normal tissues of the rectum using NMR spectroscopy].
AB  - In the present paper, NMR spectroscopy, an effective tool to detect the variation
      in molecular structure and changes in chemical composition of metabolites in
      tissues, was used to study the differences between malignant and normal tissues
      from rectum. 1H spectra of four malignant rectum tissue samples and two normal
      control tissues were investigated by using a 500M NMR high-resolution magic angle
      spinning magnetic resonance spectrometers (HR-MAS NMR). The results indicate that
      the 1H HR-MAS spectra of rectum cancer tissues are significantly different from
      those of the normal controls and most differences are presents in the form of
      variation in the relative intensities of the characteristic peak of various
      metabolites. In order to characterize the variation in the relative intensities
      in a quantitative manner, the intensity of the methyl peak of fatty acid at 0.88
      was utilized as inner standard. Systematic differences between NMR spectra of
      malignant tissue and normal controls are as follows: (1) The concentration of
      amino acid increases significantly in malignant tissues, since the relative
      intensities of characteristic peaks of amino acid including valine, isoleucine,
      leucine, lysine, glutamate, glutamine, and aspartate are stronger in the NMR
      spectra of the malignant tissues. This phenomenon may reflect the fact that the
      activity of protein synthesis is enhanced in cancerous tissues. (2) The
      intensities of the characteristic peaks of lactic acid in malignant tissues are
      higher than those from normal controls. This may be related to the nature of
      anaerobic metabolism activity in malignant tissues. (3) The level of choline and
      its derivatives, taurine and creatine, increases significantly in malignant
      tissues, suggesting that the metabolic activity of malignant tissues changes. (4)
      In the spectral region between 4.5 and 10, observable changes occur on the peaks
      for unsaturated fatty acid and nuclear acids. Therefore, the above spectral
      variations in high resolution magic angle spinning NMR spectroscopy may be
      utilized as a potential tool to diagnose rectum cancer.

PMID- 19093595
TI  - Point zero: a phenomenological inquiry into the seat of consciousness.
AB  - Does consciousness have a spatial "location" that can be scientifically
      investigated? Using a novel phenomenological method, when people are encouraged
      to explore the question introspectively they not only can make sense of the idea
      of their consciousness being "located," but will readily indicate its exact
      position inside the head. The method, based on Francisco J. Varela's work,
      involves a structured interview led by an expert mediator in which preliminary
      questions are asked of untrained volunteers about the location of objects and
      body parts, and then they are questioned about the location from which they are
      experiencing these objects. 83% of volunteers located with confidence a precise
      position for the I-that-perceives in the temporal area of the head centred midway
      behind the eyes. The same results were obtained with blind subjects (congenitally
      or later) and with non-Westerners. The significance of this subjective source of
      the experience of the location of perception is discussed linking it to
      neurological correlates of self-referred conscious activities and of conscious
      awareness in memory. Further investigations are suggested with trained volunteers
      and with individuals with psychiatric disorders.

PMID- 19093596
TI  - Effects of ambient illumination, luminance contrast, and stimulus type on
      subjective preference of VDT target and background color combinations.
AB  - This study investigated the effects of the target and background color
      combination on subjective preference, i.e., aesthetic appearance, legibility and
      visual comfort, of stimuli presented on a visual display terminal under various
      ambient illuminations, luminance contrasts, and stimulus types. Analysis showed
      the main effect of color combination was significant for the three dependent
      variables. Black-on-white and blue-on-white were the most preferred combinations,
      while turquoise-on-green and turquoise-on-red were the least preferred. A sign
      was rated better than text. The significant interaction between color combination
      and luminance contrast indicated that more preferred color combinations were
      rated better under higher luminance contrast, whereas less preferred color
      combinations had better ratings under lower luminance contrast.

PMID- 19093597
TI  - Electromyographic control of movement time in a rapid aiming movement.
AB  - One of the major issues to emerge from research on human-limb movement is the
      manner in which the central nervous system regulates electromyographic (EMG)
      activity to produce movements that differ in duration and distance. Different
      models of control predict different relations between EMG characteristics and
      movement kinematics, particularly with regard to the role of EMG burst duration
      and movement time. However, models have been evaluated with means averaged over
      individuals and across large numbers of practice trials. The goal of this study
      was to assess how well individual subjects' data conform to the predictions of
      the control models. Participants (n = 4) performed an elbow flexion and extension
      task over 45 degrees in movement times between 90 and 260 msec. EMG amplitude and
      EMG burst duration from the right elbow flexors were correlated with movement
      time for each individual. As expected, movement time was positively correlated
      with EMG burst duration and negatively correlated with EMG amplitude, with wider
      ranges in the EMG burst duration-movement time correlations across participants.
      Data from all participants supported predictions of the impulse-timing control
      model, but the slopes of the studied relations varied across participants.

PMID- 19093598
TI  - Perceived competence and enjoyment in predicting students' physical activity and
      cardiorespiratory fitness.
AB  - This study investigated the predictive strength of perceived competence and
      enjoyment on students' physical activity and cardiorespiratory fitness in
      physical education classes. Participants (N = 307; 101 in Grade 6, 96 in Grade 7,
      110 in Grade 8; 149 boys, 158 girls) responded to questionnaires assessing
      perceived competence and enjoyment of physical education, then their
      cardiorespiratory fitness was assessed on the Progressive Aerobic Cardiovascular
      Endurance Run (PACER) test. Physical activity in one class was estimated via
      pedometers. Regression analyses showed enjoyment (R2 = 16.5) and perceived
      competence (R2 = 4.2) accounted for significant variance of only 20.7% of
      physical activity and, perceived competence was the only significant contributor
      to cardiorespiratory fitness performance (R2 = 19.3%). Only a small amount of
      variance here leaves 80% unaccounted for. Some educational implications and areas
      for research are mentioned.

PMID- 19093599
TI  - Effects of increasing and decreasing intratrial stimulus speed on coincidence
      anticipation timing.
AB  - The effects of intratrial stimulus speeds on coincidence-anticipation timing was
      investigated. The Bassin Anticipation Timer was used to test 82 participants'
      response times when the intratrial stimulus speed decreased, was constant, or
      increased. Analysis showed a significant temporal directional bias with increased
      and decreased intratrial speed. Decreasing intratrial stimulus speed produced the
      greatest magnitude of error compared to constant and increasing speeds.
      Differences in response times associated with intratrial stimulus-speed changes
      may depend on participants' identifying stimulus speeds and preprogramming a
      coincident response.

PMID- 19093600
TI  - Physiological responses to violence reported in the news.
AB  - The purpose of this study was to investigate the relation between watching the
      news and activation of the autonomic nervous system. A questionnaire was
      completed, and a saliva sample was collected from each of 33 participants before
      and after viewing a news and then a comedy clip. After exposure to the news,
      cortisol levels did not increase; participants reported a significant decrease in
      joy and an increase in restlessness. Participants reported a significant decrease
      in tiredness, sadness, irritation, anxiety, and restlessness, and an increase in
      relaxation and joy after exposure to the comedy clip. Higher rates of reported
      stress in the past month were associated with significantly higher rates of
      reported feeling cold, trembling, close to tears, sweaty palms, difficulty
      breathing, and restlessness. The implications of the study and directions for
      research are discussed.

PMID- 19093601
TI  - The Mozart effect: evidence for the arousal hypothesis.
AB  - This study investigated the effect of music listening for performance on a 25
      question portion of the analytical section of the Graduate Record Exam by 72
      undergraduate students (M age 21.9 yr.). Five levels of an auditory condition
      were based on Mozart Piano Sonata No. 3 (K. 281), Movement I (Allegro); a rhythm
      excerpt; a melody excerpt; traffic sounds; and silence. Participants were
      randomly assigned to one of the stimuli. After a 5-min., 43-sec. (length of the
      first Allegro movement) listening period, participants answered the questions.
      Analysis indicated participants achieved significantly higher mean scores after
      all auditory conditions than those in the silent condition. No statistically
      significant pairwise mean difference appeared between scores for the auditory
      conditions. Findings were interpreted in terms of an arousal framework,
      suggesting the higher means in all auditory conditions may reflect immediate
      exposure to auditory stimuli.

PMID- 19093602
TI  - Development of early language and motor skills in preschool children with autism.
AB  - The present study investigated whether the onset of babbling was related (a) to
      later language ages, (b) later Fine and Gross Motor Ages, and (c) the onset of
      crawling to later language ages of preschool children with autism. Parents or
      caregivers of 32 children (6 girls, 26 boys) were given the Vineland Adaptive
      Behavior Scales to assess general adaptive behaviors. The onset of babbling and
      of first words were significantly correlated; however, babbling onset was not
      related to later language ages nor was it related to Gross and Fine Motor Ages.
      No significant correlation was observed between the onset of crawling and later
      language ages.

PMID- 19093603
TI  - Win-shift, lose-stay: contingent switching and contextual interference in motor
      learning.
AB  - Learners (n = 48) practiced three multisegment movements with distinct target
      movement times. Four practice groups were compared: blocked, random, and two
      groups who had a win-shift/lose-stay schedule (WSLS1 and WSLS2). For these latter
      groups switching between practice tasks was performance-contingent: within 5% of
      target time for 1 or 2 consecutive trials, respectively. During acquisition,
      blocked performance was more accurate than for both random and WSLS2 groups. The
      WSLS1 group performed between blocked and random groups, but did not differ from
      either. In a next-day retention test, the random group scored better than the
      blocked group. The WSLS1 group performed similarly to the random practice while
      the WSLS2 group's scores were similar to those of the blocked group. Results
      encourage further study of similar practice schedules.

PMID- 19093604
TI  - Imagery and perceptual basis of matching tasks in young children.
AB  - Object identification in perceptual tests may include constituents of mental
      rotation. A matching-to-sample task was conducted with same or different objects
      to look for evidence of rotation. Elementary schoolchildren (6 to 8 years old) in
      Grades 1 to 4 (N = 264) participated, using the inclined Flags Test and the Water
      Level Test to ensure that children can use kinematic imagery for the Flags Test
      even if they used static imagery for the Water Level Test. Performance on the
      inclined Flags Test varied by age group. Use of implicit mental rotation of the
      inclined object was inferred in recognition. Also, children at the pre
      operational stage showed a rotational effect, i.e., they could transform the
      object by turning it, thereby confirming kinematic imagery is used from age 6. As
      a consequence, solving both rotation tasks may require not only recognition of
      object frames but also objects internal to the frame.

PMID- 19093605
TI  - Deliberate practice theory: relevance, effort, and inherent enjoyment of music
      practice.
AB  - This study examined three assumptions of the theory of deliberate practice for
      practice playing music on an electronic keyboard. 40 undergraduate students,
      divided into two separate groups, practiced one of two music sequences and rated
      the relevance of practice for improving performance on the sequences, the amount
      of effort needed to learn the sequences, and the inherent enjoyment of practice
      sessions. Findings for each assumption were consistent with those suggested by
      theory but also showed that perceptions are affected by the amount of practice
      completed and performance of the skill.

PMID- 19093606
TI  - Effects of size congruency on item and size recognition with words or pictures.
AB  - The effect of size changes (8:1 or 1:8) between learning and recognition sessions
      upon item and size recognition was tested, using either pictures or words as
      stimuli. Participants (N = 34) viewed color photographs of everyday objects or
      the corresponding printed words and then performed 160 trials of a recognition
      task, including 50% new stimuli, for which they had to indicate whether each item
      had been seen before and whether its size had changed. Item recognition, for
      pictures only, was improved by size congruency between the learning and test
      sessions. In contrast, size recognition was raised by learning/test-size
      congruency for both pictures and words. Both word- and picture-learning stimuli
      produced higher item and size recognition when large in area rather than small.
      The data are interpreted as showing the stronger role of spatial coding with
      pictorial than with verbal stimuli.

PMID- 19093607
TI  - Relationship of visual perceptual deficit and motor impairment in children with
      developmental coordination disorder.
AB  - The study explored the relations of visual perceptual deficits and motor
      impairments in 60 children with Developmental Coordination Disorder (120.8 +/-
      4.0 mo.) and 60 controls (121.0 +/- 5.3 mo.), who were matched by sex (29 boys
      and 31 girls) and age. They were separately assessed on fine and gross motor
      dexterity tasks of the Movement Assessment Battery for Children, static balance
      and reaction time of lower extremities with eyes open or closed, and the Test of
      Visual-Perceptual Skills-Revised. Analysis showed the children with Developmental
      Coordination Disorder performed significantly worse than the control group, but
      only the visual perception and motor skills with timed responses were
      significantly correlated. When visual information was controlled, no significant
      correlation was noted, so motor-free visual perception appears to be
      significantly related to motor performance having a speed component in these
      children.

PMID- 19093608
TI  - Task-specific training, learning, and memory for children with developmental
      coordination disorder: a pilot study.
AB  - This pilot study compared learning and memory profiles of 20 children (55% boys;
      M age = 7.3 yr., SD = 0.4) identified as having learning difficulties and having
      or suspected of having Developmental Coordination Disorder. 10 children
      participated in a 13-wk. program of task-specific motor exercises, while the
      other 10 received none. Analysis indicated significant improvement in motor
      skills and in visuospatial working memory by the intervention group; however,
      this effect did not transfer to reading and mathematics scores. Implications
      regarding the relations among motor skills, learning, and memory are discussed
      within the context of the intervention.

PMID- 19093609
TI  - Perspective-taking skills of 6-year-old children: preschool attendance and
      mothers' and fathers' education and empathetic skills.
AB  - The purpose was to assess whether children's sex, duration of nursery school
      attendance, and mothers' and fathers' educational levels were associated with any
      statistically significant differences in perceptual, cognitive, and emotional
      perspective-taking skills. The relation between these skills and parents'
      empathetic skill was also of interest. 100 children aged 6 years (49 girls, 51
      boys) and their parents participated in the research. Data were collected through
      a Personal Information Form, the Perspective-taking Test, and the Empathetic
      Skills Scale-Form B. Analysis suggested that sex, duration of nursery school
      attendance, and mothers' and fathers' educational levels did not affect
      perspective-taking skills. There was no significant correlation between the
      perspective-taking skills of children and the empathetic skills of their parents.

PMID- 19093610
TI  - Engaging moral development and reasoning in physical education classes: comment
      on Mouratidou, et al.
AB  - Attention is given the importance of an efficacious learning context for
      promoting moral development and reasoning and awareness of risks associated with
      confounding variables, with special focus on confusing correlation with causation
      and physical education classes and educational settings with programs.

PMID- 19093611
TI  - Mixed handedness and achievement test scores of middle school boys.
AB  - The purpose of the study was to replicate findings of an earlier study of fourth
      grade boys manifesting mixed handedness with a sample. Among 32 mixed-handed boys
      in Grades 6 to 8, the right-handed writer, left-handed thrower group obtained low
      spelling scores (Normal Curve Equivalent Scores) on the California Achievement
      Test significantly more frequently than the left-handed writer, right-handed
      thrower group. These findings are consistent with data for Grade 4 boys in the
      earlier study. Findings strengthen the hypotheses that mixed handedness is not a
      unitary neuropsychological entity and that boys who write with the right hand and
      throw with the left hand might be at risk for certain academic deficits.

PMID- 19093612
TI  - Finger, sex, and side differences in fingertip size and lack of association with
      image-based digit ratio (2D:4D) measurements.
AB  - Different methods for measuring the second-to-fourth digit ratio (2D:4D), a
      putative marker for prenatal androgen exposure, may lead to varying values of
      2D:4D. Specifically, it has been hypothesized that fingertip fat pads may be
      differentially deformed when taking palm images (photocopies or flatbed scans),
      but not when fingers are measured directly, thus yielding lower 2D:4D values from
      image-based measurements rather than direct ones. A measurement protocol for
      fingertip size is unavailable, as are data on finger and sex differences in this
      trait. Introducing such a protocol, this study found very large finger
      differences in adult fingertip size (largest for 4D, smaller for 3D and 5D,
      smallest for 2D), large side differences (larger in the left than in the right
      hand of right-handed subjects), but only small and not significant sex
      differences. Fingertip size was unrelated to image-based 2D:4D measurements,
      suggesting that fingertip size and the extent of finger and sex differences
      therein are unlikely to explain discrepant 2D:4D values obtained from image-based
      versus direct measurements.

PMID- 19093613
TI  - Effects of colored light and colors of comparison stimulus and their background
      on heaviness of lifted weight.
AB  - The effects of colored light and colors of stimuli and their backgrounds on
      participants' perceptions that the weight of a stimulus was identical to a
      standard weight were examined. A total of 23 women and 19 men, Taiwanese college
      students ages 20 to 23 years (M = 21.2, SD = 0.8) were randomly divided into
      three groups, with each assigned to one of three possible colored light
      conditions. Colored light significantly affected the constant errors between
      weight perceptions of the comparison and standard stimuli; the perception
      constant errors under yellow light were significantly less than those under red
      and blue lights, and the constant errors under red light were less than those
      under blue light. Stimulus color significantly affected the constant errors,
      which were significantly greater for white, yellow, red, and blue comparison
      stimuli than for black stimuli; the constant errors were significantly greater
      for white and yellow stimuli than for red and blue. Moreover, an interactive two
      way effect of stimulus color and colored light was detected; however, no
      significant effect of color of stimulus background on constant error was
      observed. Practical applications include development of safe lifting guidelines
      and package and product design.

PMID- 19093614
TI  - People, clothing, music, and arousal as contextual retrieval cues in verbal
      memory.
AB  - Four experiments (N = 164) on context-dependent memory were performed to explore
      the effects on verbal memory of incidental cues during the test session which
      replicated specific features of the learning session. These features involved (1)
      bystanders, (2) the clothing of the experimenter, (3) background music, and (4)
      the arousal level of the subject. Social contextual cues (bystanders or
      experimenter clothing) improved verbal recall or recognition. However, recall
      decreased when the contextual cue was a different stimulus taken from the same
      conceptual category (piano music by Chopin) that was heard during learning.
      Memory was unaffected by congruent internal cues, produced by the same
      physiological arousal level (low, moderate, or high heart rate) during the
      learning and test sessions. However, recall increased with the level of arousal
      across the three congruent conditions. The results emphasize the effectiveness as
      retrieval cues of stimuli which are socially salient, concrete, and external.

PMID- 19093615
TI  - Observational learning of fly casting using traditional and virtual modeling with
      and without authority figure.
AB  - Traditional and virtual modeling were compared during learning of a multiple
      degree-of-freedom skill (fly casting) to assess the effect of the presence or
      absence of an authority figure on observational learning via virtual modeling.
      Participants were randomly assigned to one of four groups: Virtual Modeling with
      an authority figure present (VM-A) (n = 16), Virtual Modeling without an
      authority figure (VM-NA) (n = 16), Traditional Instruction (n = 17), and Control
      (n = 19). Results showed significant between-group differences on Form and Skill
      Acquisition scores. Except for one instance, all three learning procedures
      resulted in significant learning of fly casting. Virtual modeling with or without
      an authority figure present was as effective as traditional instruction; however,
      learning without an authority figure was less effective with regard to Accuracy
      scores.

PMID- 19093616
TI  - Color, dispersion, and exposure time in performance on rotated figure
      recognition.
AB  - This study investigated the effects of dispersion, color, and rotation of figures
      on recognition under varied exposure times. A total of 30 women and 15 men,
      Taiwanese college students ages 18 to 20 years (M = 19.1, SD = 1.2),
      participated. Subjects were to recognize a target figure and respond with its
      location in each stimulus by pressing a mouse button. Analysis showed that the
      effect of rotation on accuracy was significant. Accuracy for the rotation of 180
      degrees was greater than those for 60 degrees and 300 degrees. Exposure time also
      significantly influenced accuracy. The accuracy was greater for 2 and 3 sec. than
      for 1 sec. No significant effects on accuracy were associated with dispersion and
      color, and neither had any interactive effect on accuracy. Dispersion
      significantly affected the response time as response time for dispersion under
      0.4 and 0.5 conditions were shorter than those under 0.2 and 0.3 conditions.
      Significantly less response time was needed for rotation of 180 degrees than for
      60 degrees and 300 degrees conditions. Response time was longer for red figures
      than for blue, green, and yellow figures. No significant effect on response time
      was associated with duration of exposure. Two interactive two-way effects were
      found: dispersion x color of figure and dispersion x rotation. Implications for
      figure or icon design are discussed.

PMID- 19093617
TI  - Judgments of auditory-visual affective congruence in adolescents with and without
      autism: a pilot study of a new task using fMRI.
AB  - One of the most widely reported developmental deficits associated with autism is
      difficulty perceiving and expressing emotion appropriately. Brain activation
      associated with performance on a new task, the Emotional Congruence Task,
      requires judging affective congruence of facial expression and voice, compared
      with their sex congruence. Participants in this pilot study were adolescents with
      normal IQ (n = 5) and autism or without (n = 4) autism. In the emotional
      congruence condition, as compared to the sex congruence of voice and face,
      controls had significantly more activation than the Autism group in the
      orbitofrontal cortex, the superior temporal, parahippocampal, and posterior
      cingulate gyri and occipital regions. Unlike controls, the Autism group did not
      have significantly greater prefrontal activation during the emotional congruence
      condition, but did during the sex congruence condition. Results indicate the
      Emotional Congruence Task can be used successfully to assess brain activation and
      behavior associated with integration of auditory and visual information for
      emotion. While the numbers in the groups are small, the results suggest that
      brain activity while performing the Emotional Congruence Task differed between
      adolescents with and without autism in fronto-limbic areas and in the superior
      temporal region. These findings must be confirmed using larger samples of
      participants.

PMID- 19093618
TI  - Sex differences in directional asymmetry of digit length and its effects on sex
      differences in digit ratio (2D:4D).
AB  - Patterns of directional asymmetry in the length of index and ring finger (2D and
      4D) may be sexually differentiated. Martin, Puts, and Breedlove (2008) found
      leftward bias, i.e., both a longer 2D and 4D in the left than in the right hand,
      more frequently in men, whereas rightward bias occurred more frequently in women.
      Further, rightward vs leftward bias seemed a substantial source of variation in
      digit ratio (2D:4D), a putative marker for prenatal androgen levels. Given the
      generally small effects, unreplicable results, and inconsistent findings of 2D:4D
      research, these findings potentially are important as the type of directional
      digit asymmetry could moderate or obfuscate real associations between 2D:4D and
      target traits. Based on six samples totaling about 3,000 individuals, the present
      study replicated the first finding of Martin, Puts, and Breedlove (2008):
      leftward bias was more frequent among men and rightward bias more frequent among
      women. This sex effect was small. However, the present study did not replicate
      the second finding of Martin, et al. (2008): relative to participants' sex the
      contributions of leftward vs rightward asymmetry to individual variation in 2D:4D
      were smaller by orders of magnitude and not significant. Implications of these
      findings for 2D:4D research are discussed.

PMID- 19093619
TI  - Color preference and familiarity in performance on brand logo recall.
AB  - Two experiments assessed effects of color preference and brand-logo familiarity
      on recall performance. Exp. 1 explored the color preferences, using a forced
      choice technique, of 189 women and 63 men, Taiwanese college students ages 18 to
      20 years (M = 19.4, SD = 1.5). The sequence of the three most preferred colors
      was white, light blue, and black and of the three least preferred colors was
      light orange, dark violet, and dark brown. Exp. 2 investigated the effects of
      color preference based on the results of Exp. 1 and brand-logo familiarity on
      recall. A total of 27 women and 21 men, Taiwanese college students ages 18 to 20
      years (M = 19.2, SD = 1.2) participated. They memorized a list of 24 logos (four
      logos shown in six colors) and then performed sequential recall. Analyses showed
      color preference significantly affected recall accuracy. Accuracy for high color
      preference was significantly greater than that for low preferences. Results
      showed no significant effects of brand-logo familiarity or sex on accuracy. In
      addition, the interactive effect of color preference and brand-logo familiarity
      on accuracy was significant. These results have implications for the design of
      brand logos to create and sustain memory of brand images.

PMID- 19093620
TI  - Changes in elbow flexor power with intermittent contractions and various loads.
AB  - This study examined intermittent elbow flexion every 2 sec. for 1 min. using
      various loads to study the properties of muscle power output and their
      relationship to peak power, defined as the maximum power output. 18 young men
      performed intermittent explosive elbow flexion (30 times x min.(-1)) using 30%,
      40%, and 50% maximal voluntary contraction (MVC). The power outputs at 30% and
      40% MVC slightly decreased (rate of decrease from peak power to average power
      output during the 26 to 30 contractions was about 5%). However, at 50% MVC, there
      was a marked decrease (33.6%). Power output for 8 contractions was significantly
      larger at 50% MVC than at 30% and 40% MVC, but after 9 contractions there was no
      significant difference between 40% and 50% MVC. In addition, after 27
      contractions, 40% MVC was significantly larger than 30% and 50% MVC. That is, the
      tendency for power output to decrease differed among the various loads. The rate
      of decrease of power outputs showed no significant correlation with peak power
      for each load. Therefore, the rate of decrease of power output in intermittent
      contractions may help sustain the power output and cannot be evaluated as
      accurately as peak power.

PMID- 19093621
TI  - Effects of translational and rotational motions and display polarity on visual
      performance.
AB  - This study investigated effects of both translational and rotational motion and
      display polarity on a visual identification task. Three different motion types-
      heave, roll, and pitch--were compared with the static (no motion) condition. The
      visual task was presented on two display polarities, black-on-white and white-on
      black. The experiment was a 4 (motion conditions) x 2 (display polarities) within
      subjects design with eight subjects (six men and two women; M age = 25.6 yr., SD
      = 3.2). The dependent variables used to assess the performance on the visual task
      were accuracy and reaction time. Motion environments, especially the roll
      condition, had statistically significant effects on the decrement of accuracy and
      reaction time. The display polarity was significant only in the static condition.

PMID- 19093622
TI  - Assessment of English letters' legibility using image descriptors.
AB  - The study derived seven descriptors from the pixel matrices of both the uppercase
      and lowercase forms of the 26 letters in the English alphabet in the regular and
      italic versions of the most commonly used font, Times New Roman. A factor
      analysis of the seven descriptors showed that a two-factor solution of letter
      width and height explained 76.6% of the variance. Legibility threshold of the 26
      letters in the regular and italic Times Roman font and in two-case forms were
      collected to specify effects of letter width and height. 20 university students,
      10 women and 10 men, with a mean age of 24.1 yr. (SD = 1.6) participated. They
      identified letters displayed initially on a PC screen at a minimum font size and
      enlarged gradually until the participant correctly recognized the letter.
      Analysis showed letters of greater width or height were more legible than those
      of smaller width or height. Given an oblique effect, letters in the italic Times
      Roman font had significantly greater width but were less legible than those in
      the regular font.

PMID- 19093623
TI  - Sex differences of intermittent elbow flexion power using various loads.
AB  - This study was designed to clarify a sex difference in muscle power output
      properties by intermittent elbow flexion using various loads. 10 young males and
      10 young females performed intermittent elbow flexion power outputs at 30 times x
      min.(-1) for 1 min. using 30%, 40%, and 50% MVC loads. For both sexes, the
      decreasing peak power showed a similar trend between trials at all loads, and the
      reliability of each power parameter was good. The power outputs decreased largely
      with increasing load mass, and the power output in 50% MVC for males markedly
      decreased to the same level as that during the final phase in 30% MVC. Although
      the absolute value of regression coefficients for males became significantly
      larger with increasing load mass, that for females showed a significant
      difference only between 30% and 50% MVC. In 50% MVC, a large decrease for males
      was observed. Maximal peak power outputs were significantly larger with
      increasing load mass for both sexes, but for males more than for females. In both
      sexes, there were no significant differences among final powers of each load
      mass, and between total powers of 40% and 50% MVC. For the sum of every 5
      consecutive power outputs, males showed significant differences between 30% and
      40% MVC in all periods after the 6th contraction, but females did not and also
      between 30% and 50% MVC in periods after the 16th contraction. In conclusion, it
      is considered that power outputs in the latter phases in 50% MVC are affected
      largely by muscle fatigue, and an intermittent power output test with 50% MVC can
      measure sustained power (fatigue resistance) in the latter phases, but there is a
      sex difference in the tendency to decrease.

PMID- 19093624
TI  - [Treatment of the peritoneal carcinomatosis by cytoreductive surgery and
      intraperitoneal hyperthermic chemotherapy (IHPC): postoperative morbidity and
      mortality and short-term follow-up].
AB  - BACKGROUND: In order to treat the peritoneal carcinomatosis from abdominal
      neoplasms has been recently proposed complete peritonectomy associated with
      IntraPeritoneal Hyperthermic Chemotherapy (IHPC). AIM OF THE STUDY: Estimate of
      postoperative morbidity and mortality and short-term outcome. METHODS: Twenty
      four patients with peritoneal carcinomatosis or positive cytology at peritoneal
      washing were treated in our Department from January 2005 to October 2007. Primary
      tumor was ovarian carcinoma in ten patients: four cases presented peritoneal
      surface malignancies (PSM) after any time from hysteroadnexectomy related to
      primary tumor, six cases synchronous PSM. Primary tumor was gastric cancer in
      seven patients: the peritoneal washing was positive in four cases and, during
      follow-up period after gastrectomy, other two cases presented PSM. One patient
      was previously treated with ovariectomy for ovaric mass that resulted a
      Krukenberg's tumor of gastric cancer. Primary tumor was pseudomixoma peritonei in
      four patients; cytoreductive surgery and IHPC was carried as first line therapy
      in only one patient. Three patients were previously treated for colon carcinoma.
      IHPC was carried out through abdominopelvic cavity for 60 minutes using a closed
      abdomen technique. The drugs used were Mitomycin C (3.3 mg/m2/L) and Cisplatin
      (25 mg/m2/L). The intracavitary mean temperature was 41.8 degrees C. RESULTS: The
      mean Peritoneal Cancer Index (PCI) was 14. Postoperative major complications
      occurred in 7 cases (28%), postoperative minor complications occurred in 8 cases
      (32%). No patients died in the postoperative period. Mean hospital staying was
      11.5 days ( 6-35 days). After a median follow-up of 8 months (range 2-34), 14
      (58%) patients are alive and 13 are disease free. CONCLUSIONS: Our experience is
      consistent with other studies for the high rate of postoperative morbidity
      associated with treatment, but we achieved best results on mortality and post
      operative staying. CRS associated with IHPC is a good therapeutic option
      especially in ovaric-related carcinosis and PMP. It' s still debated whether it
      could be useful or not in colorectal related carcinosis, whereas there is a
      general agreement in the un uselessness of this technique in gastric cancer.

PMID- 19093625
TI  - [Comparision between a bilio-pacreatic diversion with or without gastroresection
      after 2 years of follow-up in the treatment of the pathological obesity].
AB  - Malabsorptive bariatric procedures have a long history beginning with jejunoileal
      bypass, which was first performed in 1950s. The biliopancreatic diversion (BPD)
      has gained more prominence in Europe since its introduction by Scopinaro in 1976
      The BPD has been modified and popularized by Hess in the United States and
      Marceau in Canada to include a sleeve gastrectomy and duodenal switch in order to
      decrease the incidence of marginal ulceration and iron deficiency anemia.
      Moreover the common channel was lengthened to 100 cm to decrease the incidence of
      long-term malnutrition. More recently Vassallo and coll. introduced a BPD
      associated with a transitory vertical gastroplasty (TGR). Aim of this study is to
      compare the results after 2 years follow-up in 15 obese patients who underwent
      the classical Scopinaro's BPD (group A) and 15 obese patients operated on BPD
      associated with TGR (group B).The mean preoperative BMI was 47.9 in the Group A
      and 48.6 in Group B. The BMI trend was after 6, 12 and 24 months: 39.1, 37.2,
      33.1 in Group A and 37.3, 35.5, 31.4 in Group B. We observed in BPD+TGR one case
      of acute pancreatitis and 3 case of gastric paralysis in group A. No mortality
      was registered. Patients treated by BPD+TGR had better results in terms of weight
      loss and metabolic complications.

PMID- 19093626
TI  - The recurrent goiter: prevention and management.
AB  - AIM OF THE STUDY: Conservative surgery of thyroid is followed by recurrence in 2
      to 70% of cases in an 8-20 years period. The surgical treatment of such
      recurrence is affected by higher morbidity than a primary total thyroidectomy. We
      wanted verify in our series this difference and discuss motivations for
      conservative or radical surgery of goiter. MATERIALS AND METHODS: We compared a
      series of 91 primary total thyroidectomy (A) with 11 cases of total thyroidectomy
      for recurrence (B) performed between 2001 and 2005. RESULTS: Postoperative
      complications were: Transient hypocalcemia 7 (7.69%) in A and 3 (27%) in B,
      Permanent hypocalcemia only 1 (9%) in B, Transient RLN deficit 2 (2.1%) in A and
      2 (18.1%) in B. CONCLUSIONS: Due to the need of a lifelong therapy with LT4 no
      utility is observed in conservative surgery of thyroid. Further, in primary
      surgery, differences in incidence of perioperative complications cannot be
      advocated to justify a conservative approach. Sophisticated technologies are not
      able to prevent all damages to parathyroid or to recurrent nerves when operating
      on recurrent goiter. Our experience confirms the results of a review of
      literature on this topic: the best management of recurrent goiter is its
      prevention by primary total thyroidectomy.

PMID- 19093627
TI  - Management of secondary peritonitis: our experience.
AB  - Intra-abdominal infections are a common cause of nosocomial sepsis and are
      associated with a severe morbility, mortality and sanitary economy implications,
      especially for decentrated sanitary structures. Mortality due to diffuse
      suppurative peritonitis (fom 10 to 20%) nowadays continues to be unacceptably
      high. Patients outcome is significantly influenced by early adequate surgery
      and/or peritoneal drainage: moreover, even early and adequate empiric
      antimicrobial therapy influences patients morbidity and mortality. Multiple
      empirical regimens have been proposed, but rarely supported by reliable
      randomized-controlled studies. The authors report 201 cases of patients with
      fever and meaningful peritoneal involvement occurred since August 1999 up to
      August 2005: 110 cases were conservatively treated, 91 cases were surgically
      treated. The paper summarizes IDAB (Infection Disease Advisory Board) guidelines
      inheriting management of intra-abdominal infections: empiric antimicrobial
      therapy for the most common causes of abdominal infections is proposed for low
      mid level risk patients, focusing on antibiotic treatment duration. High risk
      patients need to be evaluated paying particular attention to timely surgical
      infection source control. CONCLUSION: Despite of the progress in antimicrobial
      agents and intensive care treatment, peritonitis is still one of the most
      important infectious problems that a surgeon has to face.

PMID- 19093628
TI  - Dietary chemoprevention of colorectal cancer.
AB  - AIMS AND BACKGROUND: Colorectal cancer is the second cause of morbidity and death
      in Italy. Genetic and environmental factors, i.e. inappropriate nutrition, are
      strongly involved in the aetiology of colon cancer. In the present review the
      authors analyze the possible mechanisms by which certain nutritive factors may
      interfere with the complex process of carcinogenesis. METHODS: The authors
      identify studies by a literature search of Medline from January 1, 1970, through
      December 31, 2006. RESULTS: The mechanism of every protective compound is
      detailed, in particular the impact of antioxidant vitamins and minerals on tumor
      development. At present, the data suggest that vegetables are associated with
      lower risk and that their fbre content alone does not account for this
      association. Further, meat consumption is associated with an increased risk but
      this, too, is not explained solely by its fat content. Several microconstituents
      of the diet may be associated with reduced risk, including folate, methionine,
      calcium and vitamin D. Short chain fatty acids also contribute to colonic health.
      Nevertheless agricultural products contain several dangerous pesticides.
      Mutagenic compounds, particularly heterocyclic amines, produced when protein is
      cooked, plausibly explain the meat association. CONCLUSIONS: Healthy nutrition is
      a necessary but not sufficient condition for colon cancer prevention: accepted
      the feasibility of an accurate control on every patient's diet, fequently the
      difficulty encountered in nutritional chemoprevention is to establish individual
      metabolic profiles.

PMID- 19093629
TI  - [Management of the thoracic drainage in the thoracic traumas. Technical mistakes
      and new procedures].
AB  - OBJECTIVE: Thoracic trauma is positioned at the third place of occurrence in
      Multiple Trauma patient. The correct position of thoracic drainages are
      fundamental for a good resolution and restore of pulmonary function in our
      mechanical ventilated patients. METHODS: This retrospective analysis of a
      prospective database on a consecutive series of patients who had haemo
      pneumothorax drained immediately or into 3 hours from trauma was conducted over a
      period of 24 months. RESULTS: Of 600 of thoracic procedures we have considered 67
      chest drainages positioned from 2002 to 2004 in patients with thoracic trauma.
      Technical aspects of the thoracic drainage were analyzed. Outcome,pulmonary
      function and clinical complications were recorded. CONCLUSIONS: The Management of
      drains and thoracic tubes after many surgical procedures is highly variable. This
      procedure is easy, feasible, secure and we have recorded a reduction of costs and
      related complications.

PMID- 19093630
TI  - Lower limb veins color and spectral Doppler ultrasonography examination. An
      examination protocol.
AB  - Lower extremity's venous pathology was traditionally investigated by intravenous
      venography. Nowadays Color Doppler flow imaging is widely accepted as a well
      established, noninvasive method for the evaluation of deep pelvic and lower
      extremity's venous system. The vast majority of authors conclude that the method
      can safely replace diagnostic venography in all patients with venous thrombosis,
      thrombophlebitis and valve or communicating veins insuffciency. Optimal
      performance of Color Doppler flow imaging as a diagnostic tool for the whole
      lower limb veins requires: Proper equipment specifications and settings.
      Knowledge of regional venous anatomy. Established examination protocols.
      Evaluation of morphological and functional findings. Documentation of the
      findings. All these steps are described as a sequence of guidelines, photographs
      and multiple ultrasonographic images. Our paper can be useful to all physicians
      or sonographers involved with color Doppler studies for the evaluation of lower
      limb venous diseases and abnormalities.

PMID- 19093631
TI  - Lower gastrointestinal bleeding treated with transcatheter arterial embolization.
      Case report and review of the literature.
AB  - Acute lower gastrointestinal bleeding, is often a dramatic situation, associated
      with mortality rate up to 28%. Currently transcatheter alternatives have found
      their place in the therapeutic spectrum of this situation. An interesting
      question is when should this procedure be performed and which are the
      difficulties when performing it. We present the case of a 75-year old woman with
      acute massive lower gastrointestinal bleeding on the tenth post-operative day of
      a colic and partial ileal resection. Superselective angiography of the superior
      mesenteric artery was obtained that disclosed marked contrast extravasation of
      distal branches of the left colic artery as well as from a small branch feeding
      the distal enteric anastomoses. Clinical success was achieved after
      superselective embolization which was accomplished by using polyvinyl alcohol
      particles. The patient was discharged 5 days later and there were no procedure
      related complications during 6-month follow-up period. So, especially in post
      operative patients who are considered to be poor candidates for surgical
      treatment, arterial embolotherapy should be established not only as treatment
      option, but also as first line therapy for LGI bleeding.

PMID- 19093632
TI  - [Surgical complications of the diverticular disease. A rare case of sigmoid
      vaginal fistula].
AB  - The Authors report on a rare case of diverticular disease complicated by a
      sigmoid- vaginal fistula with personal considerations based on a review of
      literature. A 75 year old patient becomes to our observation suffering the lost
      of smelly vaginal secretions without fever or abdominalgia. In anamnesis
      hysterectomy cholecystectomy appendectomy and visceral adhesions lysis.
      Colonoscopy RX barium enema, gynaecological examination, vaginal buffer show
      diverticulis of colon sigma with sigmoid-vaginal fistula. After laparotomy,
      visceral adhesions lysis, it was done sigmoid- vaginal fistula resection with
      healing. Diverticular disease is a XX century pathology with incidence (for some
      authors) of 50% of population. Symptomatic forms affect 30-50% of patients
      (variable percentage based on age); the 1% of these need surgery. The colonic
      anatomical-functional disorder is the principal cause of diverticular disease
      that recognize the main localization in colon-sigma. Diverticulitis with
      pericolic inflammation are frequent complications; possible evolutions are local
      tamponed peritonitis, mechanical intestinal occlusion, hemorrhage from colonic
      wall and fistulas. Sigmoid-vaginal fistula is the most frequent in women
      previously treated with laparohysterectomy. The colonoscopy and RX barium enema
      are gold standard for instrumental diagnosis; the vaginography is diriment,
      urography excludes urological diseases. The surgical treatment is the fistula
      resection, with or without colonic resection. In consideration of the necessity
      of conservative surgery and on the basis of this case, the authors suggest, if
      it's possible, the simple fistula resection, although the literature report an
      high number of relapses.

PMID- 19093634
TI  - Necrotizing fasciitis. Case report.
AB  - Necrotizing fasciitis (NF) is an infection localized at the fascial structures
      (both the superficial and deep ones) layering the muscles though never affecting
      them. NF death rate is very high (20-40%). NF can be a post-surgery, traumatic or
      infective complication and its prognosis quoad vitam is fatal without a timely
      and correct therapy. A 57-year-old woman was got into observation due to her
      temperature, left thigh pain, erythema and tumefaction in the left groin-crural
      seat. She suffered from obesity, insulin-dependent mellitus diabetes and modest
      but chronic renal failure and ischaemic cardiopathy from previous Acute
      Myocardial Infarctions. It was then started a wide-spectrum antibiotics therapy.
      But after just six hours there took place a rapid development of the clinical
      picture with the appearance of haemorrhagic-content blisters and areas of
      cutaneous necrosis. The patient therefore underwent-under general anaestesia
      multiple incisions in the groin-crural seat and on the ipsilateral thigh. The
      multiple biopsies carried out during the operation too underwent cultural and
      histomorphopathological analysis. The anatomic pathological study highlighted the
      presence of necrosis of the fascia, vascular thrombosis and myonecrosis. The
      cultural analysis of the tissue biopsies showed a polymicrobial infection. Both
      the pharmacological therapy and the surgical cleaning were carried out daily but
      without any improvement of the clinical picture. On the eighth day a worsening of
      the patient's general conditions took place, with a multiple organ failure
      determining the patient's exitus.

PMID- 19093633
TI  - [Giant mucocele of the appendix. Case report and review of the literature].
AB  - INTRODUCTION: Mucocele is a rare pathology of the appendix characterized by
      expansion of the lumen for a slow storage of mucous. Represents the 0.2-0.3% of
      all the appendectomies. Clinical signs and the symptoms are similar to those of
      the acute appendicitis, while the disease is occasionally recorded and the
      diagnosis is essentially histological. AIM OF STUDY: To recall the clinical and
      anatomopathological features of mucocele evaluating the possible evolutions of
      this rare appendicular pathology according to the updating reports of the
      literature. MATERIALS AND METHODS: Study of a clinical case. DISCUSSION: In this
      study diagnostic chriteria and prognostic factors are revised. Authors evaluate
      anatomopathological classification, possibility of evolution in a preneoplastic
      and neoplastic lesion and association with other colon cancers. The surgical
      treatment is evaluated too. CONCLUSIONS: A correct preoperative mucocele
      diagnosis is emphasized as indispensable in the choice of the proper surgical
      treatment since a good prognosis is consequent to a radical treatment.

PMID- 19093635
TI  - [Spontaneous rupture of biceps brachii tendon; ultrasound diagnosis in emergency,
      apropose of two cases. Updating results of surgical repair].
AB  - The rupture of the biceps tendon has either thraumatic or spontaneous
      degenerative etiology. Degenerative tears can occur during physiological
      abduction of shoulder, just it has been verified in woman affected by
      arthromyalgic chronic pain, due to arthrosis, or lifting light weight, like the
      second case showed Clinical suspect has been confirmed by ultrasound in
      emergency, validating surgical decision, that's the only treatment for this kind
      of pathology (arthroscopic or wide open surgery).

PMID- 19093636
TI  - Regional differences in male mortality inequalities using the National Statistics
      Socio-Economic Classification, England and Wales, 2001-03.
AB  - This article represents the first use by the Office for National Statistics of
      the National Statistics Socio-economic Classification (NS-SEC) to analyse
      regional variations in inequalities in male mortality. It is part of a serie of
      articles on social inequalities in mortality by NS-SEC. Deaths in th years 2001
      03 among men aged 25-64, from all causes and selected major cause groups, are
      examined in each of the Government Office Regions of England and in Wales. The
      results provide insights into both social gradients in mortality within regions,
      and regional differences in mortality for each NS-SEC class. The socioeconomic
      differences in mortality were more marked for men in Wales, the North East and
      the North West. The regional differences in mortality were small for the most
      advantaged classes and greatest for the least advantaged classes.

PMID- 19093637
TI  - Geographical trends in infant mortality: England and Wales, 1970-2006.
AB  - At national level in England and Wales, infant mortality rates fell rapidly from
      the early 1970s and into the 1980s. Subnational areas have also experienced a
      reduction in levels of infant mortality. While rates continued to fall to 2006,
      the rate of reduction has slowed. Although the Government Office Regions
      Yorkshire and The Humber, the North West and the West Midlands and the Office for
      National Statistics local authority types Cities and Services and London
      Cosmopolitan have experienced relatively large absolute reductions in infant
      mortality, their rates remained high compared with the national average. Within
      all regions and local authority types, a strong relationship was found between
      ward level deprivation and infant mortality rates. Nevertheless, levels of infant
      mortality declined over time even in the most deprived areas with a narrowing of
      absolute differences in rates between areas. Areas in which the level of
      deprivation eased have experienced greater than average reductions in levels of
      infant mortality.

PMID- 19093638
TI  - Standardised mortality ratios--the effect of smoothing ward-level results.
AB  - Geographical indicators of mortality provide one of the most important means of
      assessing the health of populations and are particularly effective in identifying
      inequalities in health. Geographical mortality indicators have regularly been
      produced by the Office for National Statistics, but not normally for areas
      smaller than local authorities. In order to allow variations in mortality within
      local authorities to be examined, in 2006 ONS published Standardised Mortality
      Ratios (SMRs) for wards in England and Wales, based on deaths in 1999-2003. For
      mortality indicators for small populations, based on small numbers of deaths,
      there is however a risk that results will be unstable, making geographical
      patterns hard to interpret. To examine whether this problem could be overcome,
      methods for smoothing SMRs in time and space were considered, with conclusions
      published in a methodology report in 2007. This article presents results from
      that work, illustrating the geographical patterns in mortality that emerge
      following smoothing of the ward-level SMRs.

PMID- 19093639
TI  - Infant and perinatal mortality in England and Wales by social and biological
      factors, 2007.

PMID- 19093640
TI  - Excess winter mortality in England and Wales, 2007/08 (provisional) and 2006/07
      (final).

PMID- 19093641
TI  - Health expectancies in the United Kingdom, 2004-06.

PMID- 19093642
TI  - Life expectancy at birth and at age 65 by local areas in the United Kingdom, 2005
      07.

PMID- 19093643
TI  - Cancer incidence and mortality in the United Kingdom and constituent countries,
      2003-05.

PMID- 19093644
TI  - Is physical anthropology related to craniofacial growth?

PMID- 19093645
TI  - Erbium laser treatment of an impacted first mandibular premolar: a case report.
AB  - Dental impaction defines a tooth that, instead of erupting to occupy its
      functional position, is partially or totally retained and remains within the
      bone. Retained teeth can be placed in the normal arch position through a
      combination of orthodontics and conventional surgical techniques, or a
      combination of orthodontics and laser surgery, as in the case here presented of a
      14-year-old boy with an impacted first mandibular premolar, covered by bone, and
      with complete root formation and an erupted second premolar. The impacted
      premolar was surgically exposed using an Er,Cr:YSGG laser and at the same time an
      orthodontic bracket was bonded to provide traction to move the first premolar
      into its arch position.

PMID- 19093646
TI  - Enamel deproteinization and its effect on acid etching: an in vitro study.
AB  - PURPOSE: The goal of this in vitro study was to identify the topographical
      features of the enamel surface deproteinized and etched with phosphoric acid
      (H3PO4) compared to phosphoric acid alone. MATERIALS AND METHOD: Ten extracted
      lower first and second permanent molars were polished with pumice and water, and
      then divided into 4 equal buccal sections having similar physical and chemical
      properties. The enamel surfaces of each group were subjected to the following
      treatments: Group A: Acid Etching with H3PO4 37% for 15 seconds. Group AH1:
      Sodium Hypochlorite (NaOCl) 5.25% for 30 seconds followed by Acid Etching with
      H3PO4 37% for 15 seconds. Group AH2; Sodium Hypochlorite (NaOCl) 5.25% for 60
      seconds followed by Acid Etching with H3PO4 37% for 15 seconds. Results showed
      that group AH2 etching technique reached an area of 76.6 mm2 of the total
      surface, with a 71.8 mm2 (94.47%), type 1 and 2 etching pattern, followed by
      group AH1 with 55.9 mm2 out of 75.12 mm2 (74.1%), and finally group A with only
      36.8 mm2 (48.83%) out of an area of 72.7 mm2. A significant statistical
      difference (P < 0.05) existed between all groups, leading to the conclusion that
      enamel deproteinization with 5.25% NaOCl for 1 minute before H3PO4, etching
      increases the enamel conditioning surface as well as the quality of the etching
      pattern.

PMID- 19093647
TI  - Effects of antibacterial agents on dental pulps of monkeys mechanically exposed
      and contaminated.
AB  - OBJECTIVE: The purpose of this study was to compare the effectiveness of
      antibacterial agents and mineral trioxide aggregate in the healing of bacterial
      contaminated primate pulps. STUDY DESIGN: The experiment required four adult male
      primates (Cebus opella) with 48 teeth prepared with buccal penetrations into the
      pulpal tissues. The preparations were performed under general anesthesia and the
      exposed pulps were exposed to cotton pellets soaked in a bacterial mixture
      consisting of microorganisms normally found in human pulpal abscesses obtained
      from the Endodontic Clinic of UNESP. Following bacterial inoculation (30 minute
      exposure), the pulpal tissue was immediately treated with either sterile saline,
      Cipro HC Otic solution (12), diluted Buckley' formecresol solution (12) or
      Otosporin otic solution (12) for 5 minutes. After removal of the pellet,
      hemostasis was obtained and a ZOE base applied to the DFC treated pulps and the
      non-treated controls (12). After hemostasis, the other exposed pulps were covered
      with mineral trioxide aggregate (ProRoot). The pulpal bases were all covered with
      a RMGI (Fuji II LC). The tissue samples were collected at one day, two days, one
      week and over four weeks (34 days). RESULTS: Following perfusion fixation, the
      samples were demineralized, sectioned, stained and histologically graded. After
      histologic analysis, presence of neutrophilic infiltrate and areas of hemorrhage
      with hyperemia were observed. The depth of the neutrophilic infiltrate depended
      on the agent or material used. The pulpal tissue treated with Otic suspensions
      demonstrated significantly less inflammation (Kruskal Wallis non parametric
      analysis, H = 9.595 with 1 degree of freedom; P = 0.0223) than the formocresol
      and control groups. The hard tissue bridges formed over the exposure sites were
      more organized in the MTA treatment groups than in the control and ZOE groups
      (Kruskal Wallis non parametric analysis, H = 18.291 with 1 degree of freedom; P =
      0.0004). CONCLUSIONS: Otic suspensions and MTA are effective in treating
      bacterial infected pulps and stimulate the production of a hard tissue bridge
      over the site of the exposure.

PMID- 19093648
TI  - Fuji III vs. Fuji VII glass ionomer sealants--a clinical study.
AB  - Glass ionomer cements possess several properties that support their consideration
      in a wide variety of clinical applications including Pit and fissure sealants.
      The aim of this study was to compare and evaluate Fuji III and Fuji VII glass
      ionomer sealants in terms of retention, caries incidence and salivary fluoride
      release between two groups of children aged 6 and-8 years respectively. One
      hundred and ten first permanent molars were sealed and the clinical evaluation
      showed no incidence of caries. There was partial or complete retention of the
      sealant in 80% of the treated teeth in both groups at the one-year evaluation.
      Irrespective of the sealant used, the pattern of fluoride release remained
      consistent, with an initial high fluoride release followed by low prolonged
      leakage before returning to baseline value at the end of one year.

PMID- 19093649
TI  - The erosive potential of different malt drinks: an in vitro and in situ study.
AB  - OBJECTIVES: Whereas the potential effect of acidic drinks in the etiology of
      dental erosion is well recognized the role of malt drinks is unclear. The primary
      aim of the present study was to compare the in vitro erosive effect on enamel
      produced by different aromated malt drinks. A secondary objective was to compare
      their erosive effects in situ with those determined in vitro. MATERIALS AND
      METHODS: To select the malt drink for the study in situ, six commercially
      available malt drinks were examined for erosive potential in vitro. The study in
      situ was a single centre, 2-period, 2-treatment crossover study to compare the
      erosive effect of a commercially available malt drink (Test), with that of
      natural spring water (Control), over 10 day periods on 10 healthy volunteers.
      Subjects wore upper removable appliances containing two human enamel specimens
      from 9 a.m. to 4 p.m. The regimen of intake of the drinks was 250 ml at midday.
      Measurements of enamel loss were made on samples after 5 and 10 days by
      profilometry. RESULTS: The in situ study showed a statistically significant
      difference in erosive potential between the test and control beverages. No
      specimen exposed to the control beverage displayed appreciable erosion. Erosion
      occurred with the test drink, but to a variable degree between subjects.
      CONCLUSIONS: Malt drinks should be considered as potentially erosive as the
      results for enamel specimens exposed to the test beverage in the clinical study
      showed a degree of erosion that varied greatly between different participants. It
      is likely that under these conditions an increase in the degree of erosion would
      be observed in children and young people who consume malt drinks.

PMID- 19093650
TI  - Predisposing factors and prevalence of fractured anterior teeth among 12 and 16
      years old school Malaysian children.
AB  - OBJECTIVE: This study reports on the predisposing factors and prevalence of
      fractured anterior teeth among 12 and 16 years-old school children in Kubang
      Kerian, Kelantan, West Malaysia. STUDY DESIGN: A cross-sectional study was
      performed, involving 488 school children aged 12 and 16 years old and two
      calibrated dentists on the use of the World Health Organization (WHO)
      modification of Andreasen's 1999 classification. An oral examination was
      performed and all the necessary information was collected using a specified data
      collection sheet. The data was analyzed using the SPSS version 12. RESULTS: The
      response rate was 98.8%. The prevalence of fractured anterior teeth was 11.2% at
      the age of 12 and 13.4% at the age of 16. Boys experienced more fractures than
      girls (p < 0.05) among 12 year-olds but there was no gender predilection among 16
      year olds. Most children could not remember the cause of fracture (> 53.6%). Over
      80% of dental injuries were of minor type (enamel fracture not involving the
      dentin). The maxillary central incisor was the most affected (> 60%) tooth.
      Children at the age of 12 years with over jet greater than 3 mm, incompetent and
      short lip were predisposed to dental injuries (p < 0.05). There was no
      association between molar relationship and fractures (p > 0.05) in both age
      groups. CONCLUSION: The present study assessed the prevalence of dental injuries
      in 12 and 16 year old children and determined the risk factors that predispose to
      dental injuries. The possible causes and consequences of such tooth fractures
      must be highlighted to ensure esthetics and tooth longevity.

PMID- 19093652
TI  - Juvenile ossifying fibroma of maxilla: report of a case.
AB  - Juvenile ossifying fibroma (JOF) is a rare type of fibro osseous lesion affecting
      the jaws of children under 15 years of age. We report a case of an 8-year-old boy
      diagnosed with trabecular form of JOF affecting the left maxilla with brief
      description about its histopathological differential diagnosis.

PMID- 19093651
TI  - Craniofacial architectural constraints and their importance for reconstructing
      the early Homo skull KNM-ER 1470.
AB  - OBJECTIVE: Our objective is to exploit architectural constraint for the analysis
      and interpretation of craniofacial form, which we apply here to the
      reconstruction of the early Homo cranium KNM-ER 1470. We are motivated to perform
      this study because in the absence of biological criteria our preconceptions are
      likely to govern our concept of craniofacial form. STUDY DESIGN: We reassembled
      the fragmented parts--left and right halves of the calvaria and the face-
      according to mammalian craniofacial architectural constraints described by Donald
      H. Enlow and colleagues. RESULTS: When evaluated on a biological premise, KNM-ER
      1470 is found to have a more prognathic midface than commonly appreciated. The
      relationship between facial prognathism and cranial capacity also provides an
      estimate downward for this specimen, from 752cc to ca. 700cc. CONCLUSION:
      Awareness of our preconceptions is critical to the performance of relatively
      unbiased research in fields characterized by interpretations of morphology. When
      perceptual bias is relatively minimized, applied here as an architecturally
      constrained of KNM-ER 1470 craniofacial skeleton, we are able to provide the
      scientific community with a more tractable Gestalt perspective of form.

PMID- 19093653
TI  - Lingual schwannoma involving the posterior lateral border of the tongue in a
      young individual: case report.
AB  - A schwannoma, also called neurilemmoma, is a benign, encapsulated, slow growing
      tumor arising from the neural sheath's Schwann cells of the peripheral, cranial
      or autonomic nerves. The etiology is unknown, there is no gender preference and
      the tumors occur most commonly between the ages of 20 and 50 years. Approximately
      25-48% of these tumors occur in the head and neck region, with only 1% occurring
      in the mouth. The current case reports a schwannoma of the tongue, found in a 12
      year-old boy. The lesion was present for 6 months. The clinical examination
      revealed a 1.5x1.0 cm, sessile, rubbery, non-tender non-ulcerated mass on the
      right posterior lateral border of the tongue. An excisional biopsy was performed
      under local anesthesia. The histological sections showed a circumscribed
      submucosal nodule composed of spindle cells with thin wavy nuclei arranged as
      typical Antoni A (with Verocay bodies) and Antoni B areas. Nuclear palisading
      distribution (typical of a schwannoma) was readily identifiable. The patient was
      recurrence free after one year.

PMID- 19093654
TI  - Multidisciplinary management and long-term follow-up of mesiodens: a case report.
AB  - Supernumerary teeth are relatively common in the oral cavity and are
      characterized by an excessive number of teeth. The term "mesiodens" refers to a
      supernumerary tooth located in the midline of the maxilla between the central
      incisors. Mesiodens may cause a variety of pathological complications such as
      impaction of the maxillary central incisors, tooth retention or delayed eruption
      of the permanent incisors, crowding, eruption within the nasal cavity, formation
      of diastema, intraoral infection, root anomaly, root resorption of adjacent teeth
      and cyst formation accompanied by bone destruction. Therefore it is recommended
      to follow-up with regular radiographic examination. Early diagnosis minimizes
      treatment needs and prevents associated complications. The present case, followed
      for 7 years, presented bilateral mesiodens resulting in delayed eruption of the
      permanent incisors and emphasizes the importance of multidisciplinary management
      and long-term follow-up.

PMID- 19093655
TI  - Headache and transverse maxillary discrepancy.
AB  - The purpose of this study is to evaluate the usefulness of rapid palatal
      expansion in growing patients to eliminate the nasal pyramid stenosis as a cause
      of primary headache. Patients were invited to participate in the clinical study
      at the University of Milan, Department of Orthodontics. Forty-one growing
      patients of both genders suffering from primary neurovascular headaches and
      having transverse maxillary deficiency were studied before and after rapid
      palatal expansion. A clinical examination, postero-anterior radiography and
      rhinomanometry were performed. After rapid palatal expansion (RPE) therapy all
      patients showed a constant and important increase in the values relating to both
      skeletal and dental structures, a significant reduction in the mean nasal
      resistance, and a significant decrease or elimination of headache symptoms. This
      therapy provides a preventive alternative for surgical procedures, such as the
      neurovascular decompressive septo-ethmoidosphenoidectomy performed in adult
      patients.

PMID- 19093656
TI  - Relationship between malocclusion and behavioral, demographic and socioeconomic
      variables: a cross-sectional study of 5-year-olds.
AB  - OBJECTIVE: Epidemiological studies have demonstrated that the prevalence and the
      severity of malocclusion have increased over the years. The aim of this study was
      to evaluate the relationship between malocclusions, such as open bite and
      crossbite, and behavioral, demographic and socioeconomic variables in a sample of
      5-year-old children attending preschools. METHODS: The random sample consisted of
      728 preschool children attending 22 public (n = 428) and 18 private (n = 300)
      preschools. A calibrated examiner performed the epidemiological examination
      outdoors, under natural light, using dental mirror and CPI probe. Information on
      socioeconomic status and the presence of deleterious oral habits was collected by
      a questionnaire sent to parents. Univariate and multiple logistic regression
      analyses were performed. RESULTS: The deleterious oral habits were observed in
      83.1% of the children and were significantly associated with social class.
      Pacifier use (OR = 21.71), thumb sucking (OR = 4.72); atypical swallowing (OR =
      7.35) and mouth breathing (OR = 4.65) were risk indicators for open bite.
      Pacifier use (OR = 1.59), lip interposition (OR = 1.78), mouth breathing (OR =
      1.96) and gender (OR = 1.88) were risk indicators for crossbite. CONCLUSIONS:
      Environmental factors, such as the presence of deleterious oral habits as well as
      social class, play an important role in identifying children with open and/or
      crossbite.

PMID- 19093657
TI  - Changes in hyoid position following treatment of Class II division1 malocclusions
      with a functional appliance.
AB  - OBJECTIVE: The aim of this study was to determine change of hyoid bone position
      following treatment with functional appliance in patients with class II division
      1 malocclusion. DESIGN: This study performed on pre and post treatment lateral
      cephalograms of 28 patients with class II div I malocclusion treated with Farmand
      functional appliance on average of 11 months. The range of age of girls was 10-13
      years and boys 11-14 years. To study the results, t test and Pearsons correlation
      coefficient were used. RESULTS: Hyoid bone shifted significantly (P value < 0.01)
      forward in horizontal dimension and non significantly upward in vertical
      dimension. There was no significant difference between three groups in facial
      growth patterns with respect to hyoid bone position alterations in horizontal
      dimension but was significant between horizontal and vertical growth pattern in
      vertical dimension. (P value < 0.05). There was significant correlation between
      decrease ofANB angle with forward movement of hyoid bone. CONCLUSION: Following
      treatment with Farmand functional appliance, significant changes occur in the
      position and anterior displacement of the hyoid bone.

PMID- 19093658
TI  - Responding to peer reviews: pointers that authors don't learn in school.

PMID- 19093659
TI  - Experience and expertise: how do they relate to quality and safety?

PMID- 19093660
TI  - Bringing evidence to the point of care.

PMID- 19093661
TI  - Moving beyond biomedical understanding of lipodystrophy in people living with
      HIV/AIDS.
AB  - The purpose of this article is to move beyond the biomedical standpoint in the
      field of HIV/AIDS in order to contribute to the recognition oflipodystrophy as a
      phenomenon that reaches far beyond its current definition as an unfortunate side
      effect of highly active antiretroviral therapy (HAART). This article hopes to
      demonstrate how theory, while remote to the clinical setting, can allow nurses to
      understand the experience of lipodystrophy as a social phenomenon and address it
      likewise in their practice. The specific aim of this article is to apply the
      concept of stigma to the experience of lipodystrophy in people living with
      HIV/AIDS. The objective of this theoretical piece is to fill the gaps in the way
      nurses address lipodystrophy in the clinical setting and to demonstrate the
      richness of Goffman's concept of stigma (1963) in understanding the experience of
      lipodystrophy.

PMID- 19093662
TI  - Developing a positive emotion-motivated Tai Chi (PEM-TC) exercise program for
      older adults with dementia.
AB  - Exercise, particularly Tai Chi, has many known benefits, especially in reducing
      fall risk. However, exercise studies have tended to exclude older adults with
      dementia (OAD), who may be at high fall risk but have difficulty participating in
      formal exercise programs. This paper describes development and feasibility
      testing of a Tai Chi fall risk reduction exercise protocol, the positive emotion
      motivated Tai Chi (PEM-TC) program for OAD, and explores strategies that
      facilitate their participation in and adherence to exercise programs. Preliminary
      data indicates that difficulties in delivering exercise to OAD may be eased by
      using the Sticky Hands Tai Chi teaching technique. Family members may have the
      optimum advantage in using Sticky Hands because of established emotional
      connections with their OAD.

PMID- 19093663
TI  - Journeys from addiction to recovery.
AB  - Addiction affects us all. It has wide-reaching consequences for the individual,
      the family, and society as a whole. This article attempts to assist providers and
      addicts in understanding the road to recovery. Transformation from addiction to
      recovery is best explained by recovering addicts themselves. In this qualitative
      study, nine participants describe their experiences with long-term recovery. The
      transtheoretical model of change (Prochaska & DiClemente, 1983) was combined with
      Mezirow's (1997) transformative learning theory to structure a framework that
      highlights the transition of these individuals as they moved from addiction to
      recovery. This new combination model can be used to anticipate behavior, support,
      and encourage patients in the change from active addiction to a healthier
      lifestyle without drugs and alcohol.

PMID- 19093664
TI  - Exploring the concepts of vulnerability and resilience in the context of HIV
      infection.
AB  - Based on the unique physical, psychological, and social nature of HIV infection,
      clients with HIV infection have been categorized as both vulnerable and resilient
      in the existing literature. Concept exploration of vulnerability and resilience
      via an integrative literature review was conducted in order to examine the
      existing knowledge base of these concepts in the context of HIV infection. Search
      engines were employed to review the existing data-based sources of vulnerability
      and resilience with relation to HIV infection. After the integrative literature
      review, an analysis of vulnerability and resilience in the context of HIV
      infection emerged. Implications for further concept analysis, theory, research,
      and practice are presented.

PMID- 19093665
TI  - 'Groupness'.

PMID- 19093666
TI  - Eight dental New Year's resolutions.

PMID- 19093667
TI  - Let the numbers talk.

PMID- 19093668
TI  - The office lease: a practice asset often overlooked.

PMID- 19093669
TI  - Did you wash your hands?

PMID- 19093670
TI  - Walter Webb Allport. An exceptional man leads an exceptional meeting for an
      exceptional organization.

PMID- 19093671
TI  - Oh, those crazy kids.

PMID- 19093672
TI  - Religion and health.

PMID- 19093673
TI  - Reliability and validity of the brief multidimensional measure of
      religiousness/spirituality among adolescents.
AB  - BACKGROUND: Developed for use in health research, the Brief Multidimensional
      Measure of Religiousness/Spirituality (BMMRS) consists of brief measures of a
      broad range of religiousness and spirituality (R/S) dimensions. It has
      established psychometric properties among adults, but little is known about its
      appropriateness for use with adolescents. PURPOSE: We assessed the psychometric
      properties of the BMMRS among adolescents. METHOD: We recruited a racially
      diverse (85% non-White) sample of 305 adolescents aged 12-18 years (median 16
      yrs, IQR 14-17) from 3 urban medical clinics; 93 completed a retest 1 week later.
      We assessed internal consistency and test-retest reliability. We assessed
      construct validity by examining how well the measures discriminated groups
      expected to differ based on self-reported religious preference, and how they
      related to a hypothesized correlate, depressive symptoms. Religious preference
      was categorized into "No religion/Atheist" (11%), "Don't know/Confused" (9%), or
      "Named a religion" (80%). RESULTS: Responses to multi-item measures were
      generally internally consistent (alpha > or = 0.70 for 12/16 measures) and stable
      over 1 week (intraclass correlation coefficients > or = 0.70 for 14/16).
      Forgiveness, Negative R/S Coping, and Commitment items showed lower internal
      cohesiveness. Scores on most measures were higher (p < 0.05) among those who
      "Named a religion" compared to the "No religion/Atheist" group. Forgiveness,
      Commitment, and Anticipated Support from members of one's congregation were
      inversely correlated with depressive symptoms, while BMMRS measures assessing
      negative R/S experiences (Negative R/S Coping, Negative Interactions with others
      in congregation, Loss in Faith) were positively correlated with depressive
      symptoms. CONCLUSIONS: These findings suggest that most BMMRS measures are
      reliable and valid for use among adolescents.

PMID- 19093675
TI  - Work and women's well-being: religion and age as moderators.
AB  - Religion has been found to moderate the stress-strain relationship. This
      moderator role, however, may be dependent on age. The present study tested for
      the three-way interaction between work experience, age, and religiosity in the
      prediction of women's well-being, and predicted that work experience and
      religiosity will combine additively in older women, while in younger women
      religiosity is predicted to moderate the relationship between work experience and
      well-being. In a sample of 389 married Malay Muslim women, results of the
      regression analyses showed significant three-way interactions between work
      experience, age, and religiosity in the prediction of well-being (measured by
      distress symptoms and life satisfaction). While in younger women the results were
      in line with the predictions made, in the older women, both additive and
      moderator effects of religiosity were observed, depending on the well-being
      measures used. These results are discussed in relation to the literature on work
      and family, with specific reference to women's age, religion, as well as the
      issue of stress-strain specificity.

PMID- 19093676
TI  - A spiritual screening tool for older adults.
AB  - OBJECTIVE: The purpose of this non-experimental study was to investigate the
      reliability and validity of a self-administered screening tool for spiritual
      distress in older adults. The tool was unique in that items were consistent with
      a conceptual definition of spirituality presented in the professional literature
      and supported by theories of behavioral development for older adults. METHODS:
      Questionnaires were distributed to residents of a continuing care retirement
      community participating in a class on spirituality. RESULTS: The split-half
      reliability coefficient was found to be 0.776. Construct validity was established
      and a cutoff value for spiritual distress was determined. DISCUSSION: Tests for
      reliability and validity demonstrated confidence in use of the tool to screen for
      spiritual distress in older adults.

PMID- 19093674
TI  - Spiritual assessment in African-Americans: a review of measures of spirituality
      used in health research.
AB  - BACKGROUND: A number of instruments have been developed for investigating
      relationships between spirituality and health, and have been used to assess
      spirituality in African-Americans. Yet, the cultural appropriateness for African
      Americans of these instruments has not been investigated to date. OBJECTIVES: To
      evaluate the construct validity and reliability of spirituality measures used in
      health research from 1982 to 2005. METHOD: Systematic review of the literature.
      RESULTS: Thirty five studies and five measures of spirituality met the inclusion
      criteria. Most of the spirituality measures were developed in primarily Caucasian
      American samples. African-Americans were represented in 71% of the studies (n =
      25) using spirituality measures in health research. Distinct cultural attributes
      of African-American spirituality were omitted in most of the spirituality
      measures. Two studies were retrieved in which psychometric evaluation was
      conducted in entirely African-American samples. DISCUSSION: Spirituality is a
      significant cultural experience and belief that influences the health behaviors
      of African-Americans. The lack of a culturally appropriate measure of African
      American spirituality is a major limitation of studies investigating spirituality
      and health in this population. Development of a culturally appropriate and
      sensitive measure of spirituality in African-Americans is suggested to strengthen
      the quality of research in this area.

PMID- 19093677
TI  - Puja as one dimension of a sensitive, relational approach to community health
      care provision.
AB  - This article compares two projects designed to train groups of rural Rajasthani
      women as community health workers. Through ethnographic research conducted during
      the training periods of each project I highlight stark differences in the
      management and structural approaches. The successful project recognised the
      importance of rituals, specifically puja, in the daily lives of participants.
      Both the NGO management and the trainees performed daily rituals that helped
      foster a supportive network. Sensitivity combined with a wider insight into the
      practical realities and constraints facing women in rural Rajasthan contributed
      to the long-term success of the second project. The first project has folded. I
      argue a lack of open dialogue and real connection with participants meant the
      project's management were unable to adapt/tailor the program to the needs and
      experiences of the women involved.

PMID- 19093678
TI  - William James' The Varieties of Religious Experience revisited.
AB  - This essay addresses the familial, religious, and cultural context for the
      writing and presentation of William James' classic work The Varieties of
      Religious Experience. The essay emphasizes the importance of the impact of Henry
      James, Senior, upon his son. This relationship along with a severe cardiac
      condition contributed to James' taking on and carrying through with his
      exploration of religious experience. The article explores The Varieties and
      concludes with a discussion of the importance of James' use of narrative to the
      study of mind-body medicine. This paper was originally presented at the
      Richardson Research Seminar in the History of Psychiatry at Weill Cornell Medical
      College.

PMID- 19093679
TI  - Whither the psychology of religion: a spirituality-focused discussion of
      Paloutzian and Park's (2005). Handbook of the psychology of religion and
      spirituality.
AB  - Presuming Rayburn's (2006: Child & Family Behavior Therapy, 28, 86-92) review of
      (Paloutzian and Park's, (2005, New York: The Guilford Press) [corrected] Handbook
      of the Psychology of Religion and Spirituality [corrected] and sketching an
      alternative paradigm, this review focuses on the Handbook's virtual conflation of
      religion and spirituality; relates this conflation to the hegemony of Protestant
      theology in North American psychology of religion; highlights the Handbook's lack
      of attention to [corrected] spirituality per se, which--if [corrected] not
      inseparably linked with theism, but, rather, [corrected] related to the self
      transcending, meaning-making dimension of the human mind--could [corrected]
      provide an explanatory breakthrough in the field of the psychology of religion
      and of the social sciences overall; and sees Handbook's advocacy for a
      "multilevel interdisciplinary paradigm" as a regrettable acceptance of the
      failed, long-term strategy of the field of psychology in general.

PMID- 19093680
TI  - Perception and the awareness of God: the importance of neuronal habituation in
      the context of the Jewish and Christian faiths.
AB  - One of the most significant existential dilemmas for the religious person is the
      discrepancy between the assertion that God is everywhere and eternally present,
      and the inability to become aware of His presence. In this paper, we discuss how
      developments in our understanding of the brain's mechanisms for perception may
      resolve this apparent contradiction. We submit that if God is eternally present
      and unchangeable, then by the process of neuronal habituation, an individual can
      be "unaware" of the presence of God. We also discuss the limits of human
      perception and illustrate the biblical questions concerning the awareness of God.

PMID- 19093681
TI  - Appropriate spiritual care by physicians: a theological perspective.
AB  - It is argued that when spiritual care by physicians is linked to the empirical
      research indicating the salutary effect on health of religious beliefs and
      practices an unintended degradation of religion is involved. It is contended that
      it is much more desirable to see support for the patient's spirituality as part
      of holistic care. A proposal for appropriate spiritual care by physicians is
      offered.

PMID- 19093682
TI  - The mother relationship and artistic inhibition in the lives of Leonardo da Vinci
      and Erik H. Erikson.
AB  - In four earlier articles, I focused on the theme of the relationship of
      melancholia and the mother, and suggested that the melancholic self may
      experience humor (Capps, 2007a), play (Capps, 2007b), dreams (Capps, 2008a), and
      art (Capps, 2008b) as restorative resources. I argued that Erik H. Erikson found
      these resources to be valuable remedies for his own melancholic condition, which
      had its origins in the fact that he was illegitimate and was raised solely by his
      mother until he was three years old, when she remarried. In this article, I focus
      on two themes in Freud's Leonardo da Vinci and a memory of his childhood (1964):
      Leonardo's relationship with his mother in early childhood and his inhibitions as
      an artist. I relate these two themes to Erikson's own early childhood and his
      failure to achieve his goal as an aspiring artist in his early twenties. The
      article concludes with a discussion of Erikson's frustrated aspirations to become
      an artist and his emphasis, in his psychoanalytic work, on children's play.

PMID- 19093683
TI  - Alcohol and development in youth--a multidisciplinary overview. Introduction.

PMID- 19093684
TI  - The scope of the problem.
AB  - Alcohol is the drug of choice among youth, often with devastating consequences.
      Alcohol is a leading contributor to injury death, the main cause of death for
      people under age 21. Drinking early in life also is associated with an increased
      risk of developing an alcohol use disorder at some time during the life span.
      Data consistently indicate that rates of drinking and alcohol-related problems
      are highest among White and American Indian or Alaska Native youth, followed by
      Hispanic youth, African Americans, and Asians. Prevalence rates of drinking for
      boys and girls are similar in the younger age groups; among older adolescents,
      however, more boys than girls engage in frequent and heavy drinking, and boys
      show higher rates of drinking problems. This article summarizes research on the
      epidemiology of youth drinking, including the consequences of youthful drinking,
      risk and protective factors and drinking trajectories, and information on special
      populations at particular risk for drinking-related problems.

PMID- 19093685
TI  - Developmental issues in underage drinking research.
AB  - To better understand underage drinking and how it can be prevented, research is
      being conducted in a wide variety of disciplines--focusing on aspects such as
      risk and protective factors, biological processes underlying human development,
      and the impact of socioenvironmental and pharmacologic influences on these
      mechanisms. This article examines underage drinking from a developmental
      perspective, which seeks to identify critical developmental periods during which
      interventions may be especially useful. These critical periods can provide key
      opportunities to redirect the course of development and alter the life course
      trajectory of the individual.

PMID- 19093686
TI  - The effects of alcohol on physiological processes and biological development.
AB  - Adolescence is a period of rapid growth and physical change; a central question
      is whether consuming alcohol during this stage can disrupt development in ways
      that have long-term consequences. In general, the existing evidence suggests that
      adolescents rarely exhibit the more severe chronic disorders associated with
      alcohol dependence such as liver cirrhosis, hepatitis, gastritis, and
      pancreatitis. Adolescents who drink heavily, however, may experience some adverse
      effects on the liver, bone, growth, and endocrine development. Evidence also is
      mounting, at least in animal models, that early alcohol use may have detrimental
      effects on the developing brain, perhaps leading to problems with cognition later
      in life. This article summarizes the physiological effects of alcohol on
      adolescents, including a look at the long-term behavioral and physiological
      consequences of early drinking.

PMID- 19093687
TI  - Genetics, pharmacokinetics, and neurobiology of adolescent alcohol use.
AB  - Complex behaviors such as the initiation and use of alcohol result from an
      intricate interplay between genes and environment. Genes shape physiological and
      behavioral responses to alcohol that can influence the likelihood that a young
      person will begin using alcohol and that he or she will progress to problem
      drinking. Youthful alcohol use also can have an impact on unfolding developmental
      patterns, and for some, early use becomes the entry point for pathways that lead
      to problems with alcohol. This article first describes research on genes that may
      be involved in the development of alcohol problems and how genetic factors may
      contribute to adolescent alcohol use. It then examines how the changes that occur
      during adolescent development--in alcohol metabolism, in the brain, and in the
      endocrine and stress response systems--may affect how a young person experiences
      alcohol and the likelihood that he or she will develop alcohol use problems.

PMID- 19093688
TI  - Psychosocial processes and mechanisms of risk and protection.
AB  - Psychosocial research on adolescent drinking includes studies of personality and
      the impact of particular personality traits on drinking risk, expectancies (that
      is, the effects someone expects after drinking alcohol), and cognitive
      development. Although studies involving adolescents have not identified specific
      sets of personality traits that uniquely predict alcohol use, some traits have
      been shown to be associated with heavy alcohol use and alcohol use disorders.
      These traits include disinhibition or poor self-regulation, impulsiveness and
      aggression, novelty-seeking, and negative affectivity. Externalizing behaviors in
      childhood and early adolescence have been found to predict alcohol use disorders
      in early adulthood, as have certain internalizing behaviors. This article
      examines the theories and psychosocial processes thought to underlie underage
      drinking.

PMID- 19093689
TI  - Environmental and contextual considerations.
AB  - A number of environmental factors can influence an adolescent's risk for
      drinking, including parenting styles, an adolescent's choice of peer groups, and
      even whether he or she is active in after-school activities. Alcohol advertising,
      the price of alcohol, and the degree to which underage drinking laws are enforced
      also play a role. It is difficult to establish the degree to which alcohol use is
      influenced by environmental factors. This article describes some of the
      environmental influences that may increase the risk for underage drinking.

PMID- 19093690
TI  - Interventions for alcohol use and alcohol use disorders in youth.
AB  - Designing effective interventions for adolescents with alcohol use disorders
      (AUDs) presents several challenges, not the least of which is the accurate
      diagnosis of these disorders. Diagnostic criteria for AUDs have been derived
      largely from clinical and research experience with adults. When these criteria
      were tested among adolescents, numerous developmental differences were found that
      may affect the applicability of AUD criteria to this age group. Despite the
      absence of clear diagnostic criteria for use with adolescents, research has
      identified interventions that show promise for use with youth. This article
      examines both environmental- and individual-level approaches to underage drinking
      prevention, including school- and family-based programs, and macroenvironmental
      and multicomponent comprehensive interventions. Finally, it describes brief and
      complex treatment interventions.

PMID- 19093693
TI  - Constraints on the complete optimization of human motion.
AB  - In sport and exercise biomechanics, forward dynamics analyses or simulations have
      frequently been used in attempts to establish optimal techniques for performance
      of a wide range of motor activities. However, the accuracy and validity of these
      simulations is largely dependent on the complexity of the mathematical model used
      to represent the neuromusculoskeletal system. It could be argued that complex
      mathematical models are superior to simple mathematical models as they enable
      basic mechanical insights to be made and individual-specific optimal movement
      solutions to be identified. Contrary to some claims in the literature, however,
      we suggest that it is currently not possible to identify the complete optimal
      solution for a given motor activity. For a complete optimization of human motion,
      dynamical systems theory implies that mathematical models must incorporate a much
      wider range of organismic, environmental and task constraints. These ideas
      encapsulate why sports medicine specialists need to adopt more individualized
      clinical assessment procedures in interpreting why performers' movement patterns
      may differ.

PMID- 19093692
TI  - Dehydration: cause of fatigue or sign of pacing in elite soccer?
AB  - Numerous studies have suggested that dehydration is a causal factor to fatigue
      across a range of sports such as soccer; however, empirical evidence is equivocal
      on this point. It is also possible that exercise-induced moderate dehydration is
      purely an outcome of significant metabolic activity during a game. The diverse
      yet sustained physical activities in soccer undoubtedly threaten homeostasis, but
      research suggests that under most environmental conditions, match-play fluid loss
      is minimal ( approximately 1-2% loss of body mass), metabolite accumulation
      remains fairly constant, and core temperatures do not reach levels considered
      sufficiently critical to require the immediate cessation of exercise. A complex
      (central) metabolic control system which ensures that no one (peripheral)
      physiological system is maximally utilized may explain the diversity of research
      findings concerning the impact of individual factors such as dehydration on elite
      soccer performance. In consideration of the existing literature, we propose a new
      interpretative pacing model to explain the self-regulation of elite soccer
      performance and, in which, players behaviourally modulate efforts according to a
      subconscious strategy. This strategy is based on both pre-match (intrinsic and
      extrinsic factors) and dynamic considerations during the game (such as skin
      temperature, thirst, accumulation of metabolites in the muscles, plasma
      osmolality and substrate availability), which enables players to avoid total
      failure of any single peripheral physiological system either prematurely or at
      the conclusion of a match. In summary, we suggest that dehydration is only an
      outcome of complex physiological control (operating a pacing plan) and no single
      metabolic factor is causal of fatigue in elite soccer.

PMID- 19093694
TI  - Accumulated versus continuous exercise for health benefit: a review of empirical
      studies.
AB  - Current physical activity guidelines endorse the notion that the recommended
      amount of daily physical activity can be accumulated in short bouts performed
      over the course of a day. Although intuitively appealing, the evidence for the
      efficacy of accumulated exercise is not plentiful. The purpose of this review was
      to compare the effects of similar amounts of exercise performed in either one
      continuous or two or more accumulated bouts on a range of health outcomes.
      Sixteen studies met the selection criteria for inclusion in the review, in which
      at least one outcome known to affect health was measured before and after
      continuous and accumulated exercise training interventions. Where improvements in
      cardiovascular fitness were noted, most studies reported no difference in the
      alterations between accumulated and continuous patterns of exercise. In the few
      studies where a normalization of blood pressure was observed from baseline to
      post-intervention, there appear to be no differences between accumulated and
      continuous exercise in the magnitude of this effect. For other health outcomes
      such as adiposity, blood lipids and psychological well-being, there is
      insufficient evidence to determine whether accumulated exercise is as effective
      as the more traditional continuous approach. Seven short-term studies in which at
      least one health-related outcome was measured during the 0- to 48-hour period
      after a single continuous bout of exercise and a number of short bouts of
      equivalent total duration were included in the review. Many of the studies of
      such short-term effects considered the plasma triglyceride response to a meal
      following either accumulated short or continuous bouts of exercise. Collectively,
      these studies suggest that accumulated exercise may be as effective at reducing
      postprandial lipaemia. Further research is required to determine if even shorter
      bouts of accumulated exercise (<10 minutes) confer a health benefit and whether
      an accumulated approach to physical activity increases adherence among the
      sedentary population at whom this pattern of exercise is targeted.

PMID- 19093696
TI  - Natural turf surfaces: the case for continued research.
AB  - It is well documented that health and social benefits can be attained through
      participation in sport and exercise. Participation, particularly in sports,
      benefits from appropriate surface provisions that are safe, affordable and high
      quality preferably across the recreational to elite continuum. Investment,
      construction and research into artificial sports surfaces have increased to meet
      this provision. However, not all sports (e.g. golf, rugby and cricket) are suited
      to training and match-play on artificial turf without compromising some playing
      characteristics of the games. Therefore, full sport surface provision cannot be
      met without the use of natural turf surfaces, which also have an important role
      as green spaces in the built environment. Furthermore, a significant number of
      people participate in outdoor sport on natural turf pitches, although this is a
      declining trend as the number of synthetic turf surfaces increases. Despite
      natural turf being a common playing surface for popular sports such as soccer,
      rugby and cricket, few biomechanical studies have been performed using natural
      turf conditions. It is proposed that if natural turf surfaces are to help meet
      the provision of sports surfaces, advancement in the construction and
      sustainability of natural turf surface design is required. The design of a
      natural turf surface should also be informed by knowledge of surface-related
      overuse injury risk factors. This article reviews biomechanical, engineering,
      soil mechanics, turfgrass science, sports medicine and injury-related literature
      with a view to proposing a multidisciplinary approach to engineering a more
      sustainable natural turf sport surface. The present article concludes that an
      integrated approach incorporating an engineering and biomechanical analysis of
      the effects of variations in natural turf media on human movement and the effects
      of variations in human movement on natural turf is primarily required to address
      the longer-term development of sustainable natural turf playing surfaces. It also
      recommends that the use of 'natural turf' as a catch-all categorization in injury
      studies masks the spatial and temporal variation within and among such surfaces,
      which could be important.

PMID- 19093698
TI  - Therapeutic potential of vaccines in the management of hypertension.
AB  - Therapeutic vaccination is an exciting new development in hypertension, but proof
      of-concept in the clinic is not yet clearly established. Effective renin
      angiotensin system (RAS) inhibition by a twice-yearly treatment would be
      attractive in pre-hypertension, maybe even preventing hypertension itself from
      developing. However, it is hoped that proof-of-concept with a vaccine, the
      efficacy of which is easy to measure, will encourage development of more
      adventurous vaccines directed against targets such as aldosterone or completely
      novel pathways where alternative treatments are scarce or absent. Two current
      angiotensin vaccines are in development. PMD3117 is a modified angiotensin I
      coupled to keyhole limpet haemocyanin. CYT006-AngQb is a conjugate of angiotensin
      II linked to virus particles. Studies in patients with hypertension demonstrate
      some efficacy for both vaccines, but far short of what is seen with existing RAS
      inhibitors. Modification of the immunogen or adjuvant is required to boost the
      antibody titre.

PMID- 19093695
TI  - Exercise, vascular wall and cardiovascular diseases: an update (part 2).
AB  - There is much evidence extolling the virtues of physical activity on
      cardiovascular disease (CVD). The evidence derives from different population
      groups where leisure time physical activity reduced the risk of coronary heart
      disease and cardiovascular mortality in both men and women. Recent meta-analyses
      have shown that large risk reductions for both ischaemic and haemorrhagic stroke
      can be achieved by moderate or intense physical activity. There are many data
      from human and animal studies confirming a beneficial role for exercise in the
      prevention and treatment of CVD. Physical inactivity and obesity/overweight are
      not only associated with a number of health-related risk factors, but are
      considered to be independent risk factors for CVD, type 2 diabetes mellitus and
      hypertension. Clinical trials confirm that lifestyle interventions (dietary
      modification and increased physical activity) reduce the risk of progressing from
      impaired glucose tolerance to type 2 diabetes. Moreover, epidemiological studies
      indicate that the risk of hypertension increases by being overweight. Modest
      increases in exercise intensity and frequency have hypotensive effects in
      sedentary hypertensive patients. Long-term training improves endothelium
      dependent dilatation in the aorta and resistance arteries of the heart, whereas
      short-term training increases endothelial function in coronary conduit arteries.
      Overall, more scientific evidence will undoubtedly encourage the widespread
      advocacy of the clinical benefits of exercise therapy in the prevention and
      treatment of CVD.

PMID- 19093699
TI  - Current and emerging management options for hereditary angioedema in the US.
AB  - Hereditary angioedema (HAE) is a rare disorder characterized by recurrent attacks
      of swelling that may involve multiple anatomical locations. In the majority of
      patients, it is caused by a functional or quantitative defect in the C1 inhibitor
      (C1-INH), which is an important regulator of the complement, fibrinolytic,
      kallikrein-kinin and coagulation systems. Standard treatments used for other
      types of angioedema are ineffective for HAE. Traditional therapies for HAE,
      including fresh frozen plasma, epsilon-aminocaproic acid and danazol, may be well
      tolerated and effective in some patients; however, there are limitations both in
      their safety and efficacy. Several novel therapies have completed phase III
      trials in the US, including: (i) plasma-derived C1-INH replacement therapies
      (Berinert P and Cinryze); (ii) a recombinant C1-INH replacement therapy (conestat
      alfa; Rhucin); (iii) a kallikrein inhibitor (ecallantide [DX-88]); and (iv) a
      bradykinin-2-receptor antagonist (icatibant). Both Berinert P and Cinryze are
      reported to have excellent efficacy and safety data from phase III trials.
      Currently, only Cinryze has been approved for prophylactic use in the US. US FDA
      approval for other novel agents to treat HAE and for the use of Cinryze in the
      treatment of acute attacks is pending.

PMID- 19093700
TI  - Treatment of nausea and vomiting in terminally ill cancer patients.
AB  - Nausea and vomiting is a common and distressing symptom complex in patients with
      far-advanced cancer, affecting up to 60% of individuals at some stage of their
      illness. The current approach to the palliative care of patients with nausea and
      vomiting is based on identifying the cause, understanding its pathophysiology and
      knowing the pharmacology of the drugs available for its amelioration. The
      following six main syndromes are identified: gastric stasis, biochemical, raised
      intracranial pressure, vestibular, mechanical bowel obstruction and ileus. A
      careful history, focused physical examination and appropriate investigations are
      needed to elucidate the syndrome and its cause, so that therapy is rational.
      Drugs are the mainstay of treatment in terminal cancer, and the main classes of
      antiemetic agents are prokinetics, dopamine antagonists, antihistamines,
      anticholinergics and serotonin antagonists. Dexamethasone and octreotide are also
      used, especially in bowel obstruction. Non-drug measures are important in
      relieving the associated distress. Patients should be able to die comfortably,
      without tubes. Despite decades of practice affirming this approach, the evidence
      base is weak and well designed studies are urgently needed.

PMID- 19093701
TI  - Aromatase inhibitor-associated bone loss: clinical considerations.
AB  - Aromatase inhibitors (AIs) are standard treatments for postmenopausal women with
      estrogen responsive breast cancers. The mechanism of AIs, inhibition of the
      aromatase enzyme that causes decreases in endogenous estrogens, is responsible
      for bone loss and increased fractures. Screening and prevention of AI-induced
      bone loss closely follows the standard recommendations for postmenopausal
      osteoporosis. Lifestyle changes such as increasing physical activity and weight
      bearing exercise, stopping smoking, and taking adequate amounts of daily calcium
      and vitamin D promote bone and overall health. Bisphosphonates are specific
      inhibitors of osteoclasts and reduce bone loss in women treated with AIs. The
      optimal dose administration schedule and duration of bisphosphonate treatment for
      AI-induced bone loss remains undefined.

PMID- 19093702
TI  - Strategies to improve adherence and outcomes in patients with ulcerative colitis.
AB  - This review examines studies of patient adherence to 5-aminosalicylic acid
      therapy conducted outside the context of a controlled therapy trial, considers
      the reasons why patients do not adhere to their medication and its consequences,
      and interventions to improve adherence and disease outcomes. Non-adherence in the
      inflammatory bowel disease population tends to mirror other chronic illnesses, in
      the range of 40-60%. Factors that appear to affect adherence include younger age,
      single status, heavy pill burden, perception of lack of benefit and feeling
      uninformed about the effect of medication. Three important outcomes of non
      adherence include increased risk for disease activity, increased healthcare costs
      and the possible increased risk of dysplasia/colorectal cancer. Strategies to
      improve adherence include patient education and 'health literacy', along with
      discussing patient misperceptions and fears on an individual basis, decreasing
      the daily regimen and switching to high-dose formulations, and incorporating
      patient self-management techniques into practice.

PMID- 19093704
TI  - Tigecycline: in community-acquired pneumonia.
AB  - Tigecycline is a first-in-class glycylcycline, broad-spectrum, intravenous
      antibacterial developed to overcome the two major mechanisms of tetracycline
      resistance (ribosomal protection and efflux). The drug has been in use since 2005
      for complicated intra-abdominal infections, and complicated skin and soft tissue
      structure infections, but is currently being assessed in the US for community
      acquired pneumonia (CAP) in adults. In vitro, tigecycline had good activity
      against a range of Gram-positive, Gram-negative and atypical community-acquired
      respiratory tract pathogens implicated in CAP. Compared with other
      antibacterials, tigecycline has a prolonged post-antibiotic effect against key
      bacteria and a long serum elimination half-life in humans. The drug effectively
      penetrates lung tissue. The combined results of two well designed, phase III
      studies demonstrated that tigecycline 100 mg initially, followed by 50 mg every
      12 hours for 7-14 days was not inferior to recommended dosages of levofloxacin in
      the treatment of hospitalized patients with CAP. Clinical cure rates were 89.7%
      versus 86.3% in the clinically evaluable population and 81.0% versus 79.7% in the
      clinical modified intent-to-treat population. Tigecycline was generally well
      tolerated in patients with CAP.

PMID- 19093705
TI  - Bendamustine: a review of its use in the management of indolent non-Hodgkin
      lymphoma.
AB  - Bendamustine (Treanda, Ribomustin) is a bifunctional alkylating agent that also
      has potential antimetabolite properties, and only partial cross-resistance occurs
      between bendamustine and other alkylators. In patients with indolent non-Hodgkin
      lymphoma (NHL), bendamustine monotherapy achieved high objective response rates
      in those with rituximab-refractory disease in a pivotal noncomparative trial and
      a similarly designed smaller phase II study. Many of these heavily treated
      patients were also refractory to standard chemotherapy regimens. Several phase II
      trials demonstrated good response rates with single-agent bendamustine, or
      bendamustine in combination with rituximab, in patients with indolent NHL whose
      disease relapsed after (or was refractory to) chemotherapy. Phase III studies
      comparing combination regimens as first-line therapy in patients with indolent
      NHL showed no significant differences in response rates between bendamustine
      containing regimens and standard regimens included in treatment guidelines.
      Bendamustine has been generally well tolerated in clinical trials and has a low
      propensity to induce alopecia. Results of ongoing trials will help to clarify the
      optimal role of bendamustine in indolent NHL. Available data indicate that it may
      be a particularly useful treatment option as monotherapy in patients with
      indolent NHL whose disease progressed during or following rituximab-based
      therapy, many of whom are also refractory to standard chemotherapy regimens.

PMID- 19093706
TI  - Zoledronic acid: a review of its use in breast cancer.
AB  - Zoledronic acid 4 mg administered as a 15-minute infusion every 3-4 weeks is
      effective and well tolerated in the treatment of patients with breast cancer
      metastatic to bone. It is effective in reducing complications arising from
      metastatic bone disease in this patient population, with a clinical profile that
      compares favourably with that of pamidronate. Zoledronic acid administered on a
      less frequent schedule (every 3-6 months) has also shown potential in preventing
      cancer treatment-induced bone loss in pre- and postmenopausal women with breast
      cancer receiving adjuvant hormonal therapy. Preliminary data suggest that
      zoledronic acid may have antitumour effects, which may reduce the risk of overall
      disease progression in patients with malignant disease. Thus, zoledronic acid has
      a well established role as first-line treatment in patients with bone metastases
      secondary to breast cancer, and may prove useful as a preventive treatment for
      cancer treatment-induced bone loss or an adjuvant therapy in women with breast
      cancer.

PMID- 19093703
TI  - Antidepressants for the treatment of chronic pain.
AB  - Chronic pain represents one of the most important public health problems and, in
      addition to classical analgesics, antidepressants are an essential part of the
      therapeutic strategy. This article reviews available evidence on the efficacy and
      safety of antidepressants in major chronic pain conditions; namely, neuropathic
      pain, headaches, low back pain, fibromyalgia, irritable bowel syndrome (IBS) and
      cancer pain. Studies, reviews and meta-analyses published from 1991 to March 2008
      were retrieved through MEDLINE, PsycINFO and the Cochrane database using numerous
      key words for pain and antidepressants. In summary, evidence supports the use of
      tricyclic antidepressants in neuropathic pain, headaches, low back pain,
      fibromyalgia and IBS. The efficacy of the newer serotonin and norepinephrine
      reuptake inhibitors is less supported by evidence, but can be recommended in
      neuropathic pain, migraines and fibromyalgia. To date, evidence does not support
      an analgesic effect of serotonin reuptake inhibitors, but beneficial effects on
      well-being were reported in several chronic pain conditions. These results are
      discussed in the light of current insights in the neurobiology of pain, the
      reciprocal relationship between pain and depression, and future developments in
      this field of research.

PMID- 19093707
TI  - Ibandronate: a review of its use in the management of postmenopausal
      osteoporosis.
AB  - Ibandronate (ibandronic acid; Bonviva, Boniva), a nitrogen-containing
      bisphosphonate available in once-monthly oral and quarterly intravenous
      formulations for intermittent administration, has been approved for the treatment
      of osteoporosis in postmenopausal women in the EU, the US and many other
      countries worldwide. The once-monthly oral formulation has also been approved for
      the prevention of postmenopausal osteoporosis in the US. Ibandronate is an
      effective and generally well tolerated bisphosphonate that offers an alternative
      to other bisphosphonates as a first-line treatment for postmenopausal
      osteoporosis. It occupies a similar position with respect to the prevention of
      osteoporosis in postmenopausal women at risk for the disease. The once-monthly
      oral and quarterly intravenous dosage regimens have the potential to improve
      treatment adherence and persistence, and hence clinical outcomes, compared with
      more frequently administered oral bisphosphonates. Intravenous ibandronate may be
      particularly useful for postmenopausal osteoporotic women who are noncompliant
      with, or are unable to tolerate or receive, oral bisphosphonates. Thus,
      intermittent ibandronate extends the range of pharmacological therapies for the
      treatment and prevention of postmenopausal osteoporosis.

PMID- 19093709
TI  - Anisakid parasites of fishes caught on the African shelf.
AB  - Anisakids of Scomber japonicus, Trachyrincus scabrus, Sardina pilchardus,
      Merluccius polli, Trachurus trachurus, and Hoplostethus cadenati from African
      shelf are reported. Parasites were extensively studied with respect to their
      morphology and sequence analysis of the rDNA fragment (containing internal
      transcribed spacer [ITS]-1, 5.8S subunit and ITS-2); all of them are
      approximately 1,000 base pairs. Digestion of the amplified region and its
      sequencing revealed the presence of a sibling species (A. simplex s.s. and A.
      pegreffii). Still other sequences represented closely related, but not sibling,
      species, i.e., Anisakis brevispiculata, A. ziphidarum, and A. physeteris; there
      were also 2 undescribed anisakid species. These species were temporarily
      described as Anisakis sp. HC-2005 and Anisakis sp. MP-2005 (found, respectively,
      in Hoplostethus cadenati and Merluccius polli). The study shows that the
      parasitic fauna of fishes reflects not only the geographic range of anisakid
      nematodes but also the feeding behavior of the hosts serving as links in the
      parasites' life cycles.

PMID- 19093708
TI  - Teriparatide: a review of its use in osteoporosis.
AB  - Recombinant teriparatide (Forteo; Forsteo) is an anabolic (bone forming) agent.
      Studies have shown that subcutaneous teriparatide 20 microg/day is effective in
      women with postmenopausal osteoporosis, men with idiopathic or hypogonadal
      osteoporosis and patients with glucocorticoid-induced osteoporosis. Teriparatide
      improves bone mineral density (BMD) and alters the levels of bone formation and
      resorption markers; histomorphometric studies showed teriparatide-induced effects
      on bone structure, strength and quality. Subcutaneous teriparatide 20 microg/day
      administered over a treatment period of 11-21 months was effective in reducing
      the risk of fractures in and in improving BMD in men with idiopathic or
      hypogonadal osteoporosis, women with postmenopausal osteoporosis and patients
      with glucocorticoid-induced osteoporosis. Furthermore, the beneficial effects of
      teriparatide on vertebral fracture prevention and BMD appear to persist following
      treatment cessation. Teriparatide is generally well tolerated and treatment
      compliance rates are favourable. However, current limitations on the length of
      treatment and the high acquisition cost mean that teriparatide is best reserved
      for the treatment of patients with osteoporosis at high risk of fracture, or for
      patients with osteoporosis who have unsatisfactory responses to or intolerance of
      other osteoporosis therapies.

PMID- 19093710
TI  - A new species of blood fluke (Digenea: Spirorchiidae) from the Malayan box
      turtle, Cuora amboinensis (Cryptodira: Geomydidae) in Thailand.
AB  - Spirhapalum siamensis n. sp. obtained from the heart of the Malayan box turtle,
      Cuora amboinensis, from western Thailand is described. This blood fluke differs
      from the 2 previously known species of Spirhapalum in its larger overall body
      size, constricted mid-body, greater number of pre-ovarian testes, ceca that loop
      anteriorly from the cecal bifurcation before turning to the posterior, and the
      relatively smaller size of its ventral sucker. A phylogenetic analysis using
      molecular characters places the new species in the basal clade of tetrapod blood
      flukes, more derived than Spirhapalum polesianum, but less derived than
      Spirorchis spp.

PMID- 19093711
TI  - Evaluation of a pharmacist-led, medicines education program for Aboriginal Health
      Workers.
AB  - INTRODUCTION: The health of Indigenous Australians is exceptionally poor compared
      with that of non-Indigenous Australians. Cardiovascular diseases are the leading
      cause of death, the death rate being at least 2.7 times higher than the total
      Australian population. Indigenous Australians also experience underutilisation
      and reduced quality use of medicines. Aboriginal Health Workers (AHWs) are
      appropriate members of the healthcare team to provide information about medicines
      to the Indigenous community. However, despite having an expanding role in
      medicines management, AHWs have reported they do not have adequate appropriate
      education to support this role. Community pharmacists in localities with high
      Indigenous populations are well placed to provide medicines education to AHWs;
      however, to be successful in this role they need to develop their cultural
      awareness. The purpose of this study was to evaluate a culturally appropriate,
      pharmacist-led cardiovascular medicines education program for AHWs. Research
      questions included: What was the impact of the program on the pharmacists? What
      were the barriers and facilitators? Was the program useful and acceptable to the
      AHWs? METHODS: Four educational units were developed in collaboration with AHWs.
      A purposive sample of community pharmacists from western New South Wales (NSW)
      attended training involving instruction in the delivery of the program and
      cultural awareness training. The pharmacists then recruited local AHWs and
      delivered the program. Evaluation, with respect to the pharmacists, involved a
      repeated measures, three-phase questionnaire and semi-structured, face-to-face,
      in-depth interview post-program. Feedback was obtained from the AHWs in the form
      of a brief survey, and an audit of the attendance at each session was performed.
      RESULTS: Twelve pharmacists in 10 localities throughout western NSW delivered the
      program to a total of 47 AHWs. Statistically significant differences in the
      questionnaire responses, as a result of delivering the education, indicated the
      pharmacists felt better equipped to deal with Indigenous health issues (p =
      0.002, Mann-Whitney U-test); they knew more AHWs in their area (p = 0.005, Mann
      Whitney U-test); they felt more confident as educators of AHWs (p = 0.007, Mann
      Whitney U-test); and more confident that they had the necessary resources to
      deliver this education (p = 0.005, Mann-Whitney U-test). The semi-structured
      interviews revealed that the experience of delivering the education improved
      pharmacists' confidence as educators and motivated them to develop sustainable
      relationships with AHWs. A significant barrier lay in the challenges associated
      with organizing the AHW education sessions, while an important facilitator was
      prior established relationships with local Aboriginal health services. Evaluation
      with respect to the AHWs revealed the program reached 80% (n = 47/59) of AHWs
      within the western NSW region. In total, 46% (n = 27) of AHW participants
      attended all four educational units and attendance at each educational unit was
      above 78% (n = 37) throughout. The AHWs reported that they found the program
      interesting and relevant and were enthusiastic for future collaboration with the
      pharmacists. CONCLUSIONS: The desire to develop sustainable relationships was
      seen by all participants as the most positive aspect of the program.

PMID- 19093712
TI  - Baroreflex sensitivity and essential hypertension in adolescents.
AB  - It has been known for many years that baroreflex sensitivity is lowered in
      hypertensive patients. There are several known factors implicating this
      association, e.g. high blood pressure leads to remodeling of the carotid arterial
      wall, to its stiffness and to a diminished activation of baroreceptors; leptin
      released from a fatty tissue activates the sympathetic nervous system etc. On the
      other hand, low baroreflex sensitivity (BRS, usually quantified in ms/mmHg) can
      be inborn. Studies on primary hypertension in children and adolescents have
      brought new information about the role of baroreflex in the development of an
      early stage of primary hypertension. BRS lower than 3.9 ms/mmHg was found in 5 %
      of healthy subjects. This value approaches the critical value for the risk of
      sudden cardiac death in patients after myocardial infarction and corresponds to
      the value present in hypertensive patients. A decreased BRS and BRSf (baroreflex
      sensitivity expressed in mHz/mmHg, index independent of the mean cardiac
      interval), was found not only in children with hypertension, but also in those
      with white-coat hypertension. This is in accordance with a single interpretation.
      The decrease of BRS/BRSf precedes a pathological blood pressure increase. The
      contribution of obesity and BRS/BRSf to the development of hypertension in
      adolescents was also compared. Both factors reach a sensitivity and a specificity
      between 60 % and 65 %, but there is no correlation between the values of the body
      mass index and BRS either in the group of hypertensive patients or in healthy
      controls. If a receiver operating curve (sensitivity versus specificity) is
      plotted for both values together using logistic regression analysis, a
      sensitivity higher than 70 % and a specificity over 80 % are reached. This means
      that low baroreflex sensitivity is an independent risk factor for the development
      of primary hypertension. Studies demonstrate that adolescents with increased
      blood pressure and with BRS under 7 ms/mmHg should be given care and intensively
      motivated to change their lifestyle including a change in diet and increase in
      physical activity.

PMID- 19093713
TI  - Mechanisms of chronic heart failure development in end-stage renal disease
      patients on chronic hemodialysis.
AB  - More than 50 % of end-stage renal disease (ESRD) patients treated by chronic
      hemodialysis die from cardiovascular diseases, including congestive heart failure
      (CHF). The incidence of CHF is rising in both general and ESRD population.
      However, the mechanisms, which lead to the development of CHF in dialyzed
      patients, differ considerably. First, there are several factors leading to
      increase of the left ventricular afterload: volume overload between dialyses,
      hypertension, increased arterial stiffness, anemia, vascular access flow
      (arteriovenous fistula) and sympathetic activation. Second, hypertension, left
      ventricular hypertrophy, anemia and frequently present coronary artery disease
      worsen myocardial oxygenation. The combination of these factors explains the high
      incidence of CHF in dialyzed patients and their roles are reviewed in this
      article.

PMID- 19093714
TI  - Urotensin II-induced increase in myocardial distensibility is modulated by
      angiotensin II and endothelin-1.
AB  - Endogenous regulators, such as angiotensin-II (AngII), endothelin-1 (ET-1) and
      urotensin-II (U-II) are released from various cell types and their plasma levels
      are elevated in several cardiovascular diseases. The present study evaluated a
      potential crosstalk between these systems by investigating if the myocardial
      effects of U-II are modulated by AngII or ET-1. Effects of U-II (10(-8), 10(-7),
      10(-6) M) were tested in rabbit papillary muscles in the absence and in the
      presence of losartan (selective AT(1) receptor antagonist), PD-145065
      (nonselective ET-1 receptors antagonist), losartan plus PD-145065, AngII or ET-1.
      U-II promoted concentration-dependent negative inotropic and lusitropic effects
      that were abolished in all experimental conditions. Also, U-II increased resting
      muscle length up to 1.008+/-0.002 L/L(max). Correcting it to its initial value
      resulted in a 19.5+/-3.5 % decrease of resting tension, indicating increased
      muscle distensibility. This effect on muscle length was completely abolished in
      the presence of losartan and significantly attenuated by PD-145065 or losartan
      plus PD-145065. This effect was increased in the presence of AngII, resulting in
      a 27.5+/-3.9 % decrease of resting tension, but was unaffected by the presence of
      ET-1. This study demonstrated an interaction of the U-II system with the AngII
      and ET-1 systems in terms of regulation of systolic and diastolic function.

PMID- 19093715
TI  - Effect of alpha(1)-adrenergic antagonist prazosin on behavioral alterations
      induced by MK-801 in a spatial memory task in Long-Evans rats.
AB  - Animal models of neuropsychiatric disorders are current topics in behavioral
      neuroscience. Application of non-competitive antagonists of NMDA receptors (such
      as MK-801) was proposed as a model of schizophrenia, as it leads to specific
      behavioral alterations, which are partly analogous to human psychotic symptoms.
      This study examined an animal model of schizophrenia induced by a systemic
      application of MK-801 (0.15 and 0.20 mg/kg) into rats tested in the active
      allothetic place avoidance (AAPA) task. Previous studies suggested that MK-801
      may interact in vivo with other neurotransmitter systems, including noradrenergic
      system. Our experiments therefore evaluated the hypothesis that both locomotor
      stimulation and deficit in avoidance behavior in AAPA task induced by this drug
      would be reversible by application of alpha(1)-adrenergic antagonist prazosin (1
      and 2 mg/kg). The results showed that both doses of prazosin partially reversed
      hyperlocomotion induced by higher doses of MK-801 and an avoidance deficit
      measured as number of entrances into the shock sector. Interestingly, no effect
      of prazosin on the MK-801-induced decrease of maximum time between two entrances
      (another measure of cognitive performance) was observed. These results support
      previous data showing that prazosin can compensate for the hyperlocomotion
      induced by MK-801 and newly show that this partial reduction sustains even in the
      forced locomotor conditions, which are involved in the AAPA task. The study also
      shows that certain parameters of avoidance efficiency may be closely related to
      locomotor activity, whereas other measures of cognition may more selectively
      reflect cognitive changes.

PMID- 19093716
TI  - Mechanism of action of homocysteine and its thiolactone in hemostasis system.
AB  - In the article, the actions of homocysteine (Hcys) and its metabolite - cyclic
      thioester - homocysteine thiolactone (HTL) on complex process of hemostasis,
      which regulates the flowing properties of blood, are described. Possible
      interaction of Hcys and HTL with endothelial cells, blood platelets, plasmatic
      fibrinogen and plasminogen, as the important major components of hemostasis are
      also discussed. The modification of hemostatic proteins (N-homocysteinylated or S
      homocysteinylated proteins) induced by Hcys or its thiolactone, and links of
      homocysteine or homocysteine thiolactone to "NO metabolism seem to be the main
      reason of biotoxicty of homocysteine in cardiovascular diseases.

PMID- 19093717
TI  - Beta 2-band synchronization during a visual oddball task.
AB  - The study investigated whether specific changes in phase synchrony in the beta 2
      frequency band of EEG (25-35 Hz) occurred during a recognition task. The level of
      synchrony was examined between one hundred and eighty loci in the frontal and
      temporal lobes of eight epileptic patients with intracerebral electrodes; the EEG
      records were obtained during a visual oddball task. In each pair of records, the
      correlation curves were created from the sequence of correlation coefficients
      calculated. These curves consisted of irregular oscillations between the maximal
      and minimal r-values. Transient highly synchronized activity was observed during
      the whole time course of the experiment in all record pairs investigated and a
      significant relationship was found between the number of such episodes and the
      mean correlation coefficient (Spearman R 0.84; N 3240; p<0.001). On averaged
      curves, which were calculated using stimulus onsets as the trigger of averaging,
      a significant increase of the mean correlation coefficient in the post-stimulus
      epoch was found (p<0.01 after both target and non-target stimuli; t-test for
      dependent samples). As the cognitive demand significantly increases after
      stimulus presentation, the results are considered to be the first evidence from
      intracranial recording of increased synchronization in the beta 2 frequency band
      related to the cognitive activity.

PMID- 19093718
TI  - Anorexigenic effect of cholecystokinin is lost but that of CART (Cocaine and
      Amphetamine Regulated Transcript) peptide is preserved in monosodium glutamate
      obese mice.
AB  - Monosodium glutamate (MSG) treatment of neonatal mice results in a selective
      damage to the arcuate nucleus (ARC) and development of obesity with increased
      adiposity at sustained body weight in the adulthood. Feeding pattern of the MSG
      obese mice is unusual. Our previous results showed that after 24-h fasting, MSG
      mice consumed negligible amount of food in several hours and therefore, it was
      impossible to register the effect of peptides attenuating food intake such as
      cholecystokinin (CCK) or cocaine- and amphetamine-regulated transcript (CART)
      peptide. To overcome this problem, two findings were used: firstly, orexigenic
      effect of neuropeptide Y (NPY) was attenuated both by CCK or CART peptide in lean
      fed mice and secondly, orexigenic effect of NPY was preserved in fed rats with
      MSG obesity. In this study, short-term food intake in fed lean and MSG obese
      C57BL/6 male mice was measured after simultaneous central administration of
      orexigenic NPY with either CART peptide or peripherally administered CCK.
      Anorexigenic action of exogenous CART peptide was preserved in MSG obese mice. On
      the other hand, satiety effect of exogenous CCK was completely lost in MSG obese
      mice. In conclusion, effective leptin signaling in ARC is necessary for satiety
      effect of CCK.

PMID- 19093719
TI  - The effect of rosiglitazone on the expression of thrombogenic markers on
      leukocytes in type 2 diabetes mellitus.
AB  - Diabetes mellitus is associated with a number of prothrombotic abnormalities, and
      correction of these abnormalities might translate into the reduction of
      cardiovascular risk. Glitazones improve endothelial function and reduce
      inflammation, but much less is known about their effect on thrombogenic factors.
      We have therefore studied the effect of rosiglitazone on leukocyte and soluble
      thrombogenic markers in patients with type 2 diabetes mellitus. Thirty-three
      subjects with type 2 diabetes and 32 normal controls were included; patients were
      examined at baseline and after 5 months of rosiglitazone treatment (4 mg/day). We
      measured leukocyte-platelet aggregates and leukocyte expression of either P
      selectin glycoprotein ligand 1 (PSGL-1) or receptor for urokinase-type
      plasminogen activator (uPAR) using flow cytometry, as well as several circulating
      soluble thrombogenic markers by ELISA method. Leukocyte expression of uPAR and
      PSGL-1 was significantly higher in patients than in controls. Leukocyte-platelet
      aggregates and leukocyte expression of uPAR and PSGL-1 significantly decreased
      after rosiglitazone. There was also significant decrease in CRP and fibrinogen
      levels, but there was no effect of diabetes and/or rosiglitazone on other
      circulating molecules. In conclusions, we observed a substantial improvement in
      the expression of thrombogenic markers on leukocytes after rosiglitazone
      treatment, suggesting the novel antithrombotic effects of rosiglitazone.

PMID- 19093720
TI  - Ouabain-insensitive, Na(+)-stimulated ATPase of several rat tissues: activity
      during a 24 h period.
AB  - Rhythmic daily changes in the Na,K-ATPase activity have been previously described
      for rat kidney cortex, showing two peaks: at 0900 h and 2100 h, and two valleys:
      at 1500 h and 0100 h -0300 h. The oscillations in Na,K-ATPase activity are
      produced by an inhibitor, which binds the enzyme and is present in the rat blood
      plasma at valley times and absent or at very low concentrations at peak times.
      Since it has been demonstrated that active Na(+) extrusion from the cells of
      several tissues depends not only on the Na,K-ATPase but also on the ouabain
      insensitive Na-ATPase, we studied the activity of this latter enzyme of several
      rat tissues, i.e., kidney cortex, small intestine, liver, heart and red blood
      cells along the day. None of these tissues showed any variation of their Na
      ATPase activity along the day. Preincubation of kidney cortex homogenates
      obtained at 0900 h, with blood plasma drawn at 0900 h and 1500 h, did not modify
      the Na-ATPase activity. Our results indicate that the Na-ATPase activity does not
      oscillate along the day. These results are in agreement with the idea that the Na
      ATPase could partially compensate the Na(+) transport affected by oscillations of
      the Na,K-ATPase activity.

PMID- 19093721
TI  - An initial exploration of in vivo hair cortisol responses to a brief pain
      stressor: latency, localization and independence effects.
AB  - Cortisol is secreted by the central hypothalamo-pituitary-adrenal axis and
      affects many target organs and tissues, particularly in response to stressor
      demands and infection. Recent data reporting cortisol synthesis in hair follicles
      have shown the existence of a parallel "peripheral" HPA-axis. However, although
      there is evidence from in vitro studies and single-observation comparisons
      between groups that cortisol from hair follicles reflects endocrine changes
      associated with stressor demands, there are no reports to date of repeated
      measurements of in vivo cortisol responsivity in hair to transitory stressors.
      This issue was investigated with three males who underwent 1 min cold pressor
      test (CP). Cortisol response in hair to stressor demand appears to be (a) swift
      but transitory, (b) localized to the site of the demand and (c) independent of
      central HPA-axis activity.

PMID- 19093722
TI  - Regionally-selective cell colonization of micropatterned surfaces prepared by
      plasma polymerization of acrylic acid and 1,7-octadiene.
AB  - Micropatterned surfaces have been used as a tool for controlling the extent and
      strength of cell adhesion, the direction of cell growth and the spatial
      distribution of cells. In this study, chemically micropatterned surfaces were
      prepared by successive plasma polymerization of acrylic acid (AA) and 1,7
      octadiene (OD) through a mask. Rat vascular smooth muscle cells (VSMC), bovine
      endothelial cells (EC), porcine mesenchymal stem cells (MSC) or human skeletal
      muscle cells (HSKMC) were seeded on these surfaces in densities from 9,320
      cells/cm(2) to 31,060 cells/cm(2). All cell types adhered and grew preferentially
      on the strip-like AA domains. Between day 1 and 7 after seeding, the percentage
      of cells on AA domains ranged from 84.5 to 63.3 % for VSMC, 85.3 to 73.5 % for
      EC, 98.0 to 90.0 % for MSC, and 93.6 to 55.0 % for HSKMC. The enzyme-linked
      immunosorbent assay (ELISA) revealed that the concentration of alpha-actin per mg
      of protein was significantly higher in VSMC on AA. Similarly, immunofluorescence
      staining of von Willebrand factor showed more apparent Weibel-Palade bodies in EC
      on AA domains. MSC growing on AA had better developed beta-actin cytoskeleton,
      although they were less stained for hyaluronan receptor (CD44). In accordance
      with this, MSC on AA contained a higher concentration of beta-actin, although the
      concentration of CD44 was lower. HSKMC growing on AA had a better developed alpha
      actin cytoskeleton. These results based on four cell types suggest that plasma
      polymerization is a suitable method for producing spatially defined patterned
      surfaces for controlled cell adhesion, proliferation and maturation.

PMID- 19093723
TI  - Cognitive functions and drug sensitivity in adult male rats prenatally exposed to
      methamphetamine.
AB  - The aim of the present study was to investigate the impact of prenatal
      methamphetamine (MA) exposure and application of the same drug in adulthood on
      cognitive functions of adult male rats tested in Morris water maze (MWM). Adult
      male rats prenatally exposed to MA (5 mg/kg), saline or no injection were
      examined. Half of the animals were injected daily with MA (1 mg/kg) after
      finishing the testing. Three types of tests were used: (1) "Place navigation
      test" (Learning), (2) "Probe test" and (3) "Retention memory test" (Memory). Our
      results showed that prenatal MA exposure did not affect the test of learning and
      the Probe test. In the test of memory prenatally MA-exposed rats showed smaller
      search errors and used spatial strategies more than both control groups. Further,
      MA application in adulthood prolonged trajectories, increased the incidence of
      random search and decreased the incidence of direct swim in the Place navigation
      test. In addition, MA administration in adulthood increased the speed of swimming
      regardless of prenatal exposure. The present study thus demonstrates that 1)
      Prenatal MA exposure does not affect learning in the MWM, 2) Prenatal MA exposure
      improves performance in the Retention memory test in the MWM, and 3) MA
      application in adulthood impairs learning in the Morris water maze.

PMID- 19093724
TI  - K(ATP) channels are involved in regulatory volume decrease in rat cardiac
      myocytes.
AB  - Regulatory volume decrease (RVD) is essential for the survival of animal cells.
      The aim of this study was to observe the RVD process in rat ventricular myocytes,
      and to determine if the K(ATP) channels are involved in the RVD process in these
      cells. By using reverse transcriptase polymerase chain reaction and Western blot
      analysis, we demonstrated that there are two types of K(ATP) channels expressed
      in rat ventricular myocytes: Kir6.1 and Kir6.2. When rat cardiac myocytes were
      exposed to hypotonic solution, cell volume increased significantly within 15 min
      and then gradually recovered. This typical RVD process could be inhibited by a
      Cl(-) channel blocker (0.5 mM 9-anthracene-carboxylic acid?9-AC), a K(+) channel
      blocker (5.0 mM CsCl) and a K(ATP) channel blocker glibenclamide (10 microM).
      Electrophysiological results showed that hypotonic solution activated a whole
      cell current, which had similar biophysical characteristics with K(ATP) opener
      (pinacidil)-induced currents. This current could be blocked by glibenclamide. Our
      data suggested that the RVD process in rat ventricular myocytes is dependent on
      the activation of K(+) channels, and that K(ATP) channels are involved in this
      process.

PMID- 19093725
TI  - Peroxidative damage of mitochondrial respiration is substrate-dependent.
AB  - The concentration-dependence of tert-butyl hydroperoxide (BHP) inhibitory effect
      on oxygen consumption in isolated rat liver mitochondria was measured in the
      presence of various respiratory substrates. Strong inhibitory effect at low
      concentrations of BHP (15-30 microM) was found for oxoglutarate and palmitoyl
      carnitine oxidation. Pyruvate and glutamate oxidation was inhibited at higher
      concentrations of BHP (100-200 microM). Succinate oxidation was not affected even
      at 3.3 mM BHP. Determination of mitochondrial membrane potential has shown that
      in the presence of NADH-dependent substrates the membrane potential was
      dissipated by BHP but was completely restored after addition of succinate. Our
      data thus indicate that beside peroxidative damage of complex I also various
      mitochondrial NADH-dependent dehydrogenases are inhibited, but to a different
      extent and with different kinetics. Our data also show that succinate could be an
      important nutritional substrate protecting hepatocytes during peroxidative
      damage.

PMID- 19093726
TI  - Is postconditioning effective in prevention against long-lasting myocardial
      ischemia in the rabbit?
AB  - The goal of the study was to determine whether postconditioning protects against
      different ischemia durations in the rabbit. Rabbits were assigned to a 20-, 25-,
      45- or 60-min coronary occlusion followed by 24-h of reperfusion. Rabbits
      received no further intervention (control) or were postconditioned with four
      cycles of 30-s occlusion and 30-s reperfusion after myocardial infarction. Plasma
      levels of troponin I were quantified throughout reperfusion. In control
      conditions, infarct sizes (% area at risk using triphenyltetrazolium chloride)
      after 20, 25, 45 and 60 min of coronary occlusions were 23+/-3, 51+/-4, 70+/-3
      and 81+/-3 %, respectively. With 20 and 25 min occlusion, postconditioning
      reduced infarct size by 43+/-10 and 73+/-21 %, respectively. On the other hand,
      with 45 or 60 min occlusion, postconditioning had no significant effects on
      infarct size (61+/-3 and 80+/-2 % of area at risk). Preconditioning protocol was
      performed with 25- and 60-min coronary occlusion. As expected, preconditioning
      significantly reduced infarct size. In conclusion, in the rabbit, the
      cardioprotection afforded by postconditioning is limited to less than 45 min
      coronary occlusion.

PMID- 19093727
TI  - GnRH-I and GnRH-II-induced calcium signaling and hormone secretion in neonatal
      rat gonadotrophs.
AB  - Two forms of gonadotropin-releasing hormone (GnRH), GnRH-I and GnRH-II, are
      commonly present in mammals. The main hormone controlling reproduction is GnRH-I
      acting through its receptor (GnRHR-I), whereas the function of GnRH-II is
      unknown. In primates, it has been suggested that GnRH-II is a specific agonist
      for the structurally distinct GnRHR-II. Here we compared effects of GnRH-I and
      GnRH-II on intracellular calcium and gonadotropin hormone release in neonatal rat
      gonadotrophs in vitro and the dependence of agonist actions on cyclic nucleotide
      levels. Both agonists elevated intracellular calcium and stimulated gonadotropin
      secretion in a concentration-dependent manner, with comparable peak amplitudes,
      but GnRH-I was three times more potent than GnRH-II. Antide, a specific GnRHR-I
      antagonist, completely blocked the action of both agonists on gonadotropin
      release. Inhibition of adenylyl cyclase activity by melatonin and MDL
      significantly attenuated GnRH-I- and GnRH-II-induced calcium signaling and
      gonadotropin release, whereas inhibition of soluble guanylyl cyclase activity was
      ineffective. GnRH-II also generated calcium oscillations in a fraction of
      gonadotrophs not expressing melatonin receptors. These results indicate that GnRH
      I and GnRH-II act on the same GnRHR to stimulate gonadotropin release through
      intracellular calcium and cyclic nucleotide signaling, and that GnRH-II is less
      potent agonist for this receptor in neonatal rat gonadotrophs.

PMID- 19093728
TI  - Time-course of tissue factor plasma level in patients with acute coronary
      syndrome.
AB  - Enhanced expression of tissue factor (TF) may result in thrombosis contributing
      to acute clinical consequences of coronary artery disease. Several studies
      demonstrated elevated plasma levels of TF in patients with acute coronary
      syndrome (ACS). The aim of our study was to compare the concentrations of TF in
      coronary sinus (CS), proximal part of the left coronary artery (LCA) and
      peripheral vein (PV) of patients with ACS and stable coronary artery disease
      (SCAD). Time course of the TF plasma levels in PV was followed on day 1 and day 7
      after index event of ACS presentation and was compared to day 0 values. No
      heparin was given prior to the blood sampling. Twenty-nine patients in the ACS
      group (age 63.6+/-10.8 years, 20 males, 9 females) and 24 patients with SCAD (age
      62.3+/-8.1 years, 21 males, 3 females) were examined. TF plasma level was
      significantly higher in patients with ACS than in those with SCAD (239.0+/-99.3
      ng/ml vs. 164.3+/-114.2 ng/ml; p=0.016). There was no difference in TF plasma
      levels in PV, CS and LCA (239.0+/-99.3 ng/ml vs. 253.7+/-131.5 ng/ml vs. 250.6+/
      116.4 ng/ml, respectively). TF plasma levels tended to decrease only non
      significantly on the day 7 (224.4+/-109.8 ng/ml). Significant linear correlation
      between TF and high sensitivity CRP (hs-CRP) levels on day 0 was found. In
      conclusion, TF plasma levels are elevated in patients with ACS not only locally
      in CS but also in systematic circulation. Our data support the relationship
      between TF production and proinflammatory mediators.

PMID- 19093729
TI  - The comparison of antioxidant and hematological properties of N-acetylcysteine
      and alpha-lipoic acid in physically active males.
AB  - The aim of this study was to follow up whether the modification of pro
      antioxidant status by oral thiol administration such as N-acetylcysteine and
      alpha-lipoic acid affects the hematological response. Twenty-eight healthy men
      participated in two independent experiments. Subjects were randomly assigned to
      one of four groups: controls (C(NAC) and C(ALA)), N-acetylcysteine (NAC) and
      alpha-lipoic acid (ALA). 1200 mg of N-acetylcysteine, 600 mg of alpha-lipoic acid
      or placebo were administered for 8 days in two doses. NAC or ALA administration
      significantly elevated plasma total antioxidant status (TAS) and reduced protein
      carbonylation (PC) and lipid peroxidation (TBARS) by more than 30 %. The reduced
      glutathione (GSH) and hematological parameters changed only in response to NAC
      administration. NAC significantly elevated the level of GSH (+33%), EPO (+26%),
      Hb (+9%) and Hct (+9%) compared with C(NAC). The mean corpuscular volume (MCV)
      and the mean corpuscular hemoglobin (MCH) also increased by more than 12% after
      NAC. The numerous negative or positive correlations between the measures of TAS,
      PC, TBARS and hematological parameters were found, which suggest the NAC-induced
      interaction between pro-antioxidant and hematological values. Our study has shown
      that both N-acetylcysteine and alpha-lipoic acid intake reveal an antioxidant
      action, but only N-acetylcysteine improves the haematological response.

PMID- 19093730
TI  - The effects of 17beta estradiol, 17alpha estradiol and progesterone on oxidative
      stress biomarkers in ovariectomized female rat brain subjected to global cerebral
      ischemia.
AB  - Neuroprotective effects of estrogens and progesterone have been widely studied in
      various experimental models. The present study was designed to compare possible
      neuroprotective effects of 17alpha-estradiol, 17beta-estradiol, and progesterone
      on oxidative stress in rats subjected to global cerebral ischemia. Global
      cerebral ischemia was induced in ovariectomized female rats by four vessel
      occlusion for 10 min. Following 72 h of reperfusion, levels of malondialdehyde
      (MDA, oxidative stress marker), and reduced glutathione (GSH, major endogenous
      antioxidant) were assessed in hippocampus, striatum and cortex of rats treated
      with either 17alpha-estradiol, 17beta-estradiol, progesterone or estradiol +
      progesterone beforehand. Steroid administration ameliorated ischemia-induced
      decrease in GSH and increase in MDA levels. Our data offers additional evidence
      that estrogens and progesterone or combination of two exert a remarkable
      neuroprotective effect reducing oxidative stress.

PMID- 19093731
TI  - Neurovascular compression: sympathetic activity in severe arterial hypertension.
AB  - Compression of the rostral ventrolateral medulla oblongata (RVLM) by an
      abnormally located artery is regarded as one possible cause of arterial
      hypertension. There exists a limited set of data suggesting that increased
      sympathetic activity in patients with RVLM compression may lead to arterial
      hypertension. Accordingly, we decided to assess the sympathetic activity in
      patients with severe arterial hypertension and to investigate any correlation
      with the presence of RVLM compression. Sixty-four patients with severe arterial
      hypertension were enrolled in our study. Sympathetic activity was evaluated using
      24-hour urinary norepinephrine as measured by high-pressure liquid chromatography
      with electrochemical detection. The presence of RVLM compression was assessed
      with magnetic resonance imaging. Neurovascular compression of the RVLM was
      identified in 40 patients, 27 of whom presented left-sided compression. Twenty
      four hour urinary norepinephrine averaged 263.6+/-135.9 nmol in patients with
      neurovascular compression - 255.6+/-137.3 nmol in those with left-sided
      compression and 251.6+/-138.5 nmol in patients without RVLM compression. We did
      not identify any increase in urinary norepinephrine in patients with severe
      arterial hypertension and neurovascular compression of the RVLM. Our results do
      not support the hypothesis that neurovascular compression of RVLM may exhibit a
      sympathetically mediated increase in blood pressure.

PMID- 19093732
TI  - Differential vulnerability of outer and inner hair cells during and after oxygen
      glucose deprivation in organotypic cultures of newborn rats.
AB  - Ischemia can contribute to the inner ear pathology and hearing loss. To determine
      the susceptibility of inner and outer hair cells (IHCs/OHCs) to ischemic and post
      ischemic period, we used organotypic cultures of the organ of Corti isolated from
      P3 rats as an in vitro model of inner ear ischemia (oxygen-glucose deprivation,
      OGD). We identified the hair cells (HCs) by phalloidin staining. The cells with
      damaged cellular membrane integrity were identified by propidium iodide (PI)
      exclusion assay. The cells with fragmented chromosomal DNA were detected by TUNEL
      assay. Organotypic cultures were subjected to a mild (3 h duration) or severe (4
      h duration) OGD, followed by a recovery period of 21 h and 20 h, respectively.
      Mild OGD induced a loss of 10-20% HCs, whereas severe OGD induced loss of 35%
      HCs. We confirmed that OHCs are less vulnerable to OGD than IHCs. Of all missing
      OHCs, 80-90% was lost during the OGD period and 10-20% during the recovery
      period. In contrast, the loss of IHCs was equal during both experimental periods.
      The OGD period was mainly associated with PI-positive nuclei. TUNEL-positive
      nuclei were a minor fraction during the OGD period and increased during the
      recovery period, indicating the progression of DNA fragmentation. Our results
      implicate a differential susceptibility of IHCs and OHCs during and after
      ischemia-like insult, which may be of therapeutic consequence.

PMID- 19093733
TI  - Extracellular hypotonicity induces disturbance of sodium currents in rat
      ventricular myocytes.
AB  - Hypotonic solution alters ion channel activity, but little attention has been
      paid to voltage-dependent sodium channels. The aim of this study was to
      investigate the effects of hypotonic solution on transient sodium currents
      (I(NaT)) and persistent sodium currents (I(NaP)). We also explored whether the
      intracellular signal transduction systems participated in the hypotonic
      modifications of sodium currents. I(NaT) and I(NaP) were recorded by means of
      whole-cell patch-clamp technique in isolated rat ventricular myocytes. Our
      results revealed that hypotonic solution reduced I(NaT) and simultaneously
      augmented I(NaP) with the occurrence of interconversion between I(NaT) and
      I(NaP). Hypotonic solution shifted steady-state inactivation to a more negative
      potential, prolonged the time of recovery from inactivation, and enhanced
      intermediate inactivation (I(IM)). Ruthenium red (RR, inhibitor of TRPV4),
      bisindolylmaleimide VI (BIM, inhibitor of PKC), Kn-93 (inhibitor of Ca/CaMKII)
      and BAPTA (Ca(2+)-chelator) inhibited the effects of hypotonic solution on I(NaT)
      and I(NaP). Therefore we conclude that hypotonic solution inhibits I(NaT),
      enhances I(NaP) and I(IM) with the effects being reversible. TRPV4 and
      intracellular Ca(2+), PKC and Ca/CaMKII participate in the hypotonic
      modifications of sodium currents.

PMID- 19093734
TI  - Effects of adenosine A1 receptor antagonism on lipogenesis and lipolysis in
      isolated rat adipocytes.
AB  - Adenosine is secreted from adipocytes, binds to adenosine A(1) receptor and
      modulates various functions of these cells. In the present study, the effects of
      an adenosine A(1) receptor antagonist (DPCPX; 0.01, 0.1 and 1 microM) on
      lipogenesis, glucose transport, lipolysis and the antilipolytic action of insulin
      were tested in rat adipocytes. DPCPX had a very weak effect on lipogenesis and
      did not significantly affect glucose uptake. In adipocytes incubated with 1
      microM DPCPX, lipolysis increased. This effect was blunted by insulin and by a
      direct inhibitor of protein kinase A. Moreover, 0.1 microM DPCPX substantially
      enhanced the lipolytic response to epinephrine and increased cAMP in adipocytes.
      However, DPCPX was ineffective when lipolysis was stimulated by direct activation
      of protein kinase A. Adipocyte exposure to epinephrine and insulin with or
      without 0.1 microM DPCPX demonstrated that this antagonist increased the release
      of glycerol. However, despite the presence of DPCPX, insulin was able to reduce
      lipolysis. It is concluded that DPCPX had a weak effect on lipogenesis, whereas
      lipolysis was significantly affected. The partial antagonism of adenosine A(1)
      receptor increased lipolysis in cells incubated with epinephrine alone and
      epinephrine with insulin due to the synergistic action of 0.1 microM DPCPX and
      epinephrine.

PMID- 19093735
TI  - Use of allogenic stem cells for the prevention of bone bridge formation in
      miniature pigs.
AB  - This study appears from an experiment previously carried out in New Zealand white
      rabbits. Allogenic mesenchymal stem cells (MSCs) were transplanted into an
      iatrogenically-created defect in the lateral section of the distal physis of the
      left femur in 10 miniature pigs. The right femur with the same defect served as a
      control. To transfer MSCs, a freshly prepared porous scaffold was used, based on
      collagen and chitosan, constituting a compact tube into which MSCs were
      implanted. The pigs were euthanized four months after the transplantation. On
      average, the left femur with transplanted MSCs grew more in length (0.56+/-0.14
      cm) compared with right femurs with physeal defect without transplanted MSCs
      (0.14+/-0.3 cm). The average angular (valgus) deformity of the left femur had an
      angle point of 0.78 degrees , following measurement and X-ray examination,
      whereas in the right femur without transplantation it was 3.7 degrees. The
      initial results indicate that preventive transplantation of MSCs into a physeal
      defect may prevent valgus deformity formation and probably also reduce disorders
      of the longitudinal bone growth. This part of our experiment is significant in
      the effort to advance MSCs application in human medicine by using pig as a model,
      which is the next step after experimenting on rabbits.

PMID- 19093736
TI  - Emerging role of interleukin-1 in cardiovascular diseases.
AB  - There is an increasing evidence linking dysbalance between various
      proinflammatory mediators and higher risk of cardiovascular events and
      pathologies. Likewise, some of the cardiovascular diseases lately appeared to
      have an autoimmune component. Interleukin-1 (IL-1), a master regulator of diverse
      inflammatory processes in higher eukaryotes and the key player in numerous
      autoimmune disorders including rheumatoid arthritis, diabetes mellitus or
      systemic sclerosis, has recently been proved to be involved in development of
      several cardiovascular diseases as well. This report aims to give a summary on
      current knowledge about the IL-1 signaling pathways and about the implication of
      IL-1 and the IL-1 receptor antagonist (IL-1Ra) in some of the diseases of the
      cardiovascular system.

PMID- 19093737
TI  - Effect of protein kinase C and protein kinase A inhibitors on contraction of
      isolated femoral arteries of SHR and Wistar rats.
AB  - Alterations of calcium handling and other second messenger cascades including
      protein kinase C (PKC) and A (PKA) were suggested to be responsible for abnormal
      vascular function in spontaneously hypertensive rats (SHR). However, the relative
      contribution of these pathways to vasoconstriction is still not completely
      understood. We investigated the effect of Ro 31-8220 (PKC inhibitor) and H89 (PKA
      inhibitor) on vasoconstriction induced by 120 mM KCl or by addition of 10 microM
      noradrenaline (NA) in isolated femoral arteries of control Wistar rats and SHR.
      Moreover, we investigated these responses in the presence and absence of Ca(2+)
      ions in the incubation medium in order to assess the role of calcium influx in
      these contractions. We observed that while the vasoconstriction in the presence
      of calcium was not different between Wistar and SHR, the difference between
      constriction elicited by NA addition in the absence and presence of external
      calcium was larger in SHR. The inhibition of PKC had no effect on constrictions
      in SHR, but diminished constrictions in Wistar rats. PKA inhibition slightly
      enhanced constrictions in Wistar rats, but reduced them in the presence of
      calcium in SHR. We conclude that vasoconstriction elicited by adrenergic
      stimulation is more dependent on extracellular calcium influx in SHR compared to
      Wistar rats. Moreover, the activation of PKA contributes to this calcium
      dependent vasoconstriction in SHR but not in Wistar. On the other hand, PKC
      activation seems to play a less important role in vasoconstriction in SHR than in
      Wistar rats.

PMID- 19093738
TI  - Serum visfatin levels in patients with anorexia nervosa and bulimia nervosa.
AB  - Visfatin is an adipose tissue-derived hormone shown to correlate with visceral
      fat mass in patients with obesity. Its possible role in patients with different
      types of eating disorders is unknown. We measured fasting serum levels of
      visfatin and leptin and surrogate measures of insulin sensitivity in 10 untreated
      patients with anorexia nervosa (AN), 10 untreated patients with bulimia nervosa
      (BN) and 20 age-matched healthy women (C) to study the possible role of visfatin
      in these disorders. Patients with AN had severely decreased body mass index (BMI)
      and body fat content. BMI of BN group did not significantly differ from that of C
      group, whereas body fat content of BN group was significantly lower compared to C
      and higher compared to AN group, respectively. Serum glucose levels did not
      significantly differ among the groups studied, whereas serum insulin and leptin
      levels and HOMA index were significantly decreased in AN group relative to both C
      and BN group. In contrast, serum visfatin levels in both patients with AN and BN
      did not differ from those of C group. We conclude that circulating visfatin
      levels are not affected by the presence of chronic malnutrition in AN or
      binge/purge eating behavior in BN.

PMID- 19093739
TI  - Association of the -344T/C aldosterone synthase gene variant with essential
      hypertension.
AB  - The aldosterone synthase gene (CYP11B2) is an important candidate gene region in
      essential hypertension. We therefore studied the association of -344T/C
      polymorphism of the CYP11B2 gene with the presence and severity of hypertension
      in a case-control study. We studied 369 individuals, of whom 213 were
      hypertensive patients (139 controlled hypertensive, 74 resistant hypertensive)
      and 156 were healthy normotensive subjects. The -344T/C polymorphism of the
      CYP11B2 gene was determined using polymerase chain reaction - restriction
      fragment length polymorphism analysis. The distribution of genotypes in
      normotensive controls and hypertensive subjects were: TT 25.6 vs. 31.9 %, TC 51.9
      vs. 57.3 % and CC 22.4 vs. 10.8 %. The -344T/C variant was associated with
      hypertension. Subjects carrying the -344T allele had a greater risk of
      hypertension compared to those having C allele (chi(2)=5.89, p<0.05). The
      frequency of CC genotype was significantly lower in hypertensive patients than in
      normotensive controls (chi(2)=9.44, p<0.01). A stepwise logistic regression
      analysis confirmed these findings. We did not find an association of -344T/C
      variant with the resistance of hypertensive patients to combination therapy, but
      we observed an association of -344T/C polymorphism of aldosterone synthase gene
      with increased risk of hypertension. These results support a potential role of 
      344T/C CYP11B2 gene polymorphism in genetic predisposition to develop
      hypertension.

PMID- 19093740
TI  - Plasma prohepcidin as a negative acute phase reactant after large cardiac surgery
      with a deep hypothermic circulatory arrest.
AB  - Hepcidin is a key regulator of iron metabolism and a mediator of anemia in
      inflammation. Recent in vitro studies recognized prohepcidin as a type II acute
      phase protein regulating via interleukin-6. The aim of the present study was to
      investigate the time course of plasma prohepcidin after a large cardiac surgery
      in relation to IL-6 and other inflammatory parameters. Patients with chronic
      thromboembolic hypertension (n=22, males/females 14/8, age 51.9+/-10.2 years)
      underwent pulmonary endarterectomy using cardiopulmonary bypass and deep
      hypothermic circulatory arrest were included into study. Arterial concentrations
      of prohepcidin, IL-1beta, IL-6, IL-8, tumor necrosis factor-alpha, and C-reactive
      protein were measured before/after sternotomy, after circulatory arrest, after
      separation from bypass, and then 12, 18, 24, 36, 48 h and 72 h after the
      separation from bypass. Hemodynamic parameters, hematocrit and markers of iron
      metabolism were followed up. Pulmonary endarterectomy induced a 48% fall in
      plasma prohepcidin; minimal concentrations were detected after separation from
      cardiopulmonary bypass. Prohepcidin decline correlated with an extracorporeal
      circulation time (p<0.01), while elevated IL-6 levels were inversely associated
      with duration of prohepcidin decline. Postoperative prohepcidin did not correlate
      with markers of iron metabolism or hemoglobin concentrations within a 72-h period
      after separation from CPB. Prohepcidin showed itself as a negative acute phase
      reactant during systemic inflammatory response syndrome associated with a cardiac
      surgery. Results indicate that the evolution of prohepcidin in postoperative
      period implies the antagonism of stimulatory effect of IL-6 and contraregulatory
      factors inhibiting prohepcidin synthesis or increasing prohepcidin clearance.

PMID- 19093741
TI  - Characterization of a functional NTPDase in the endoplasmic reticulum of rat
      submandibular salivary gland.
AB  - Nucleotidase activity and Ca-uptake were characterized in endoplasmic reticulum
      (ER) enriched rat submandibular gland (SMG) microsomal preparations. (i) Ca
      uptake had characteristics of an ER Ca-ATPase. (ii) Nucleotidase activity was
      equally stimulated by calcium, magnesium and manganese, but with different Km
      values. (iii) Specific inhibitors of P-type Ca-ATPases were ineffective on
      nucleotidase activity, demonstrating that this activity was not related to
      calcium uptake and did not correspond to classical Ca(2+) pumps. (iv) ATP and UTP
      were more efficient substrates, whereas ADP and UDP were hydrolyzed at
      significantly slower rate. (v) Nucleotidase activity was sensitive to mild
      detergent solubilization and insensitive to ionophore addition. (vi) Nucleotidase
      activity was strongly inhibited by suramin, a nucleoside triphosphate
      diphosphohydrolase (NTPDase) inhibitor. (vii) Nucleotidase activity exponentially
      diminished as function of time. All these observations are consistent with a
      NTPDase identity. The presence of a NTPDase was demonstrated by
      immunohistochemistry in rat SMG. Immunoreactivity was stronger in ductal cells
      than in mucous and serous acini. Although this enzyme was observed in the plasma
      membrane, colocalization with the ER marker calnexin revealed a specific
      subcellular localization in this organelle of all three types of cell. The
      putative function of this NTPDase activity in salivary glands is discussed.

PMID- 19093742
TI  - Presyncopal cardiac contractility and autonomic activity in young healthy males.
AB  - We investigated non-invasively cardiac contractility and autonomic nervous
      activity during presyncopal orthostatic stress induced in healthy humans. A
      graded orthostatic stress (GOS) paradigm, consisting of head-up tilt (HUT)
      combined with lower body negative pressure (LBNP) of increasing magnitude, was
      used to reach a presyncopal end-point in 15 healthy adults. Continuous beat-to
      beat hemodynamic and autonomic parameters were recorded. From supine control (C1)
      to presyncope (PS), total peripheral resistance index (TPRI) decreased from
      2300+/-500 to 1910+/-320 dyne*s*m(2)/cm(5) (p=0.004), index of contractility (IC)
      from 59+/-14 to 27+/-6 1000/s (p<0.0001), left ventricular working index (LVWI)
      from 5.2+/-1.3 vs. 3.6+/-0.6 mmHg*L/(min*m(2)) (p=0.0001) and acceleration index
      (ACI) from 65+/-18 vs. 54+/-15 100/s(2) (p=0.04). Low frequency variation of
      diastolic blood pressure (LF(nu)dBP) increased from 51+/-14 to 67+/-11 %
      (p=0.0006) and of systolic blood pressure (LF(nu)sBP) from 50+/-6 vs. 67+/-8 %
      (p<0.0001). High frequency variation of RR-interval (HF(ms(2))RRI) decreased from
      385+/-320 to 38+/-43 ms(2) (p=0.001). From late GOS (G3) to PS, TPRI decreased
      from 2540+/-640 to 1910+/-320 dyne*s*m(2)/cm(5) (p=0.003), IC from 35+/-6 to 27+/
      6 1000/s (p=0.003), LVWI from 4.6+/-0.9 to 3.6+/-0.6 mmHg*L/(min/m(2)) (p=0.003),
      LF(nu)sBP from 71+/-8 to 67+/-8 % (p=0.03), LF(mmHg(2))dBP from 6.6+/-4.0 to
      4.8+/-2.9 mmHg(2) (p=0.0001), LF(mmHg(2))sBP from 9.7+/-7.8 to 7.4+/-4.8 mmHg(2)
      (p=0.01). HF(nu)RRI increased from 19+/-8 to 28+/-13 % (p=0.008). Myocardial
      contractility indices and parameters of sympathetic activity were reduced in the
      presyncopal state, while parasympathic activity was increased. This suggests a
      decrease in cardiac contractility during orthostatically induced presyncope in
      healthy subjects.

PMID- 19093743
TI  - The effect of ketamine and saffan on the beta-endorphin and ACTH response to
      hemorrhage in the minipig.
AB  - The endocrine response is an important component of the physiological response to
      blood loss. There is some variability in reported levels of certain hormones
      during hemorrhage such as the stress hormone adrenocorticotrophic hormone (ACTH).
      Therefore, the effect of two anesthetic agents, ketamine and saffan, on ACTH and
      beta-endorphin levels during hemorrhage was assessed in 12 minipigs. The animals
      were divided into two groups, group I saffan and group II ketamine (n=6). Pigs
      were subjected to a continuous fixed volume hemorrhage under one of the above
      anesthetics while spontaneously breathing. Blood pressure and heart rate
      responses were recorded together with beta-endorphin and ACTH levels both before
      and at 10, 20, 30, 40 min after the onset of bleeding. ACTH levels were higher in
      the ketamine-anesthetized pigs and rose significantly faster with falling blood
      pressure than ACTH measured in pigs under saffan anesthesia. In contrast, the
      hemorrhage induced beta-endorphin increase was not significantly different
      between the two anesthetic groups. These results indicate that choice of
      anesthetic agent is important when investigating the hormone response to
      hemorrhage and may account for the variable hormone levels in the published
      literature to date.

PMID- 19093744
TI  - ETB2 receptor subtype stimulation relaxes the iris sphincter muscle.
AB  - Effects of ET(B) receptor stimulation and its subcellular pathways were evaluated
      in carbachol pre-contracted rabbit iris sphincter muscles (n=51). ET(B)
      stimulation with sarafotoxin (SRTX-c; 10(-10)-10(-6) M) was tested in the absence
      (n=7) or presence of 10(-5) M of: BQ-788 (ET(B2) receptor antagonist; n=6), L-NA
      (NOS inhibitor; n=7) or indomethacin (cyclooxygenase inhibitor; n=10). Effects of
      ET(B) stimulation by endothelin-1 (ET-1; 10(-10)-10(-7) M) in the presence of an
      ET(A) receptor antagonist (BQ-123; 10(-5) M; n=7) and of ET(B1) stimulation by
      IRL-1620 (10(-10)-10(-7) M; n=7) were also tested. Finally, the effects of SRTX-c
      (10(-9)-10(-7) M) in electric field stimulation (EFS) contraction were evaluated
      (n=7). ET(B) receptor stimulation by SRTX-c or ET-1 in presence of BQ-123
      promoted a concentration-dependent relaxation of the rabbit iris sphincter muscle
      by 10.8+/-2.0% and 9.4+/-1.8%, respectively. This effect was blocked by BQ-788 (
      2.3+/-2.0 %), L-NA (4.5+/-2.3 %) or indomethacin (2.3+/-2.9 %). Selective ET(B1)
      stimulation by IRL-1620 did not relax the iris sphincter muscle (0.9+/-5.4 %).
      EFS elicited contraction was not altered by SRTX-c. In conclusion, ET(B) receptor
      stimulation relaxes the carbachol precontracted iris sphincter muscle, an effect
      that is mediated by the ET(B2) receptor subtype, through NO and the release of
      prostaglandins.

PMID- 19093745
TI  - Differential regulation of galectin expression/reactivity during wound healing in
      porcine skin and in cultures of epidermal cells with functional impact on
      migration.
AB  - The glycophenotyping of mammalian cells with plant lectins maps aspects of the
      glycomic profile and disease-associated alterations. A salient step toward
      delineating their functional dimension is the detection of endogenous lectins.
      They can translate sugar-encoded changes into cellular responses. Among them, the
      members of the lectin family of galectins are emerging regulators of cell
      adhesion, migration and proliferation. Focusing on galectins-1, -3 and -7, we
      addressed the issue whether their expression is regulated during wound healing in
      porcine skin as model. A conspicuous upregulation is detected for galectin-1 in
      the dermis and a neoexpression in the epidermis, where an increased level of
      galectin-7 was also found. Applying biotinylated tissue lectins as probes, the
      signal intensities for accessible binding sites decreased, intimating an
      interaction of the cell lectin with reactive sites. In contrast, galectin-3
      parameters remained rather constant. Of note, epidermal cells in culture also
      showed an increase in expression/presence of galectin-1, measured on the levels
      of mRNA and protein, in this case by Western blotting and quantitative
      immunocytochemistry. Used as matrix, galectin-1 conferred resistance to trypsin
      treatment to attached human keratinocytes and reduced migration into scratch
      wound areas in vitro. This report thus presents new information on endogenous
      lectins in wound healing and differential regulation among the three tested
      cases.

PMID- 19093746
TI  - Formation of a vitreous phase at the surface of some commercial diatomaceous
      earth prevents the onset of oxidative stress effects.
AB  - To understand the effect of the commercial processing of diatomaceous earths
      (DEs) on their ultimate surface structure and potential toxicity, we investigated
      the influence of the industrial processing and the nature of the deposit. Two
      flux calcined specimens from different deposits, DE/1-FC and DE/2-FC, and the
      simply calcined sample DE/1-C, from the same deposit as DE/1-FC, were compared in
      both their bulk and their surface properties. X-ray diffraction (XRD) analysis in
      a heating chamber revealed the presence of cristobalite in all samples, more
      abundant on the flux calcined ones. The crystal lattice is probably imperfect, as
      the alpha-beta transition, visible by XRD in DE/1-FC and DE/2-FC, is not detected
      by differential scanning calorimetry. Progressive etching with HF solutions
      suggests that most of the crystalline phase is at the core and not at the outer
      region of the samples. The combined use of spectroscopic (UV-vis and IR) and
      calorimetric techniques (heat of adsorption of water as a measure of
      hydrophilicity) reveals that DE/1-FC and DE/2-FC particles have an external layer
      of glass, absent in DE/1-C, where iron impurities act as network-forming and
      sodium ions as modifier species, with few patches of a hydrophobic phase, the
      latter relatable to a heated pure silica phase. When tested on a macrophage cell
      line (MH-S) in comparison with appropriate positive and negative controls (an
      active and an inactive quartz dust, respectively), only DE/1-C exhibited a cell
      damage and activation similar to that of active quartz (measured by lactate
      dehydrogenase release, peroxidation of membrane lipids and synthesis of NO). It
      is likely that the presence of a vitreous phase mitigates or even eliminates the
      cellular responses of silica in DE.

PMID- 19093749
TI  - Segregation of molecules in lipid bilayer spreading through metal nanogates.
AB  - A new methodology for nanoscopic molecular filtering was developed using a
      substrate with a periodic array of metallic nanogates with various widths between
      75 and 500 nm. A self-spreading lipid bilayer was employed as the molecular
      transport and filtering medium. Dye-labeled molecules doped in the self-spreading
      lipid bilayer were filtered after the spreading less than a few tens of
      micrometers on the nanogate array. Quantitative analysis of the spreading
      dynamics suggests that the filtering effect originates from the formation of the
      chemical potential barrier at the nanogate region, which is believed to be due to
      structural change such as compression imposed on the spreading lipid bilayer at
      the gate. A highly localized chemical potential barrier affects the ability of
      the doped dye-labeled molecules to penetrate the gate. The use of the self
      spreading lipid bilayer allows molecular transportation without the use of any
      external field such as an electric field as is used in electrophoresis. The
      present system could be applied micro- and nanoscopic device technologies as it
      provides a completely nonbiased filtering methodology.

PMID- 19093748
TI  - Nitrogen substituent polarity influences dithiocarbamate-mediated lipid
      oxidation, nerve copper accumulation, and myelin injury.
AB  - Dithiocarbamates have a wide spectrum of applications in industry, agriculture,
      and medicine, with new applications being investigated. Past studies have
      suggested that the neurotoxicity of some dithiocarbamates may result from copper
      accumulation, protein oxidative damage, and lipid oxidation. The polarity of a
      dithiocarbamate's nitrogen substituents influences the lipophilicity of the
      copper complexes that it generates and thus potentially determines its ability to
      promote copper accumulation within nerve and induce myelin injury. In the current
      study, a series of dithiocarbamate-copper complexes differing in their
      lipophilicity were evaluated for their relative abilities to promote lipid
      peroxidation determined by malondialdehyde levels generated in an ethyl
      arachidonate oil-in-water emulsion. In a second component of this study, rats
      were exposed to either N,N-diethyldithiocarbamate or sarcosine dithiocarbamate;
      both generated dithiocarbamate-copper complexes that were lipid- and water
      soluble, respectively. Following the exposures, brain, tibial nerve, spinal cord,
      and liver tissue copper levels were measured by inductively coupled mass
      spectroscopy to assess the relative abilities of these two dithiocarbamates to
      promote copper accumulation. Peripheral nerve injury was evaluated using grip
      strengths, nerve conduction velocities, and morphologic changes at the light
      microscope level. Additionally, the protein expression levels of glutathione
      transferase alpha and heme-oxygenase-1 in nerve were determined, and the quantity
      of protein carbonyls was measured to assess levels of oxidative stress and
      injury. The data provided evidence that dithiocarbamate-copper complexes are
      redox active and that the ability of dithiocarbamate complexes to promote lipid
      peroxidation is correlated to the lipophilicity of the complex. Consistent with
      neurotoxicity requiring the formation of a lipid-soluble copper complex,
      significant increases in copper accumulation, oxidative stress, and myelin injury
      were produced by N,N-diethyldithiocarbamate but not by sarcosine dithiocarbamate.

PMID- 19093750
TI  - Kinetics membrane disruption due to drug interactions of chlorpromazine
      hydrochloride.
AB  - Drug-membrane interactions assume considerable importance in pharmacokinetics and
      drug metabolism. Here, we present the interaction of chlorpromazine hydrochloride
      (CPZ) with supported phospholipid bilayers. It was demonstrated that CPZ binds
      rapidly to phospholipid bilayers, disturbing the molecular ordering of the
      phospholipids. These interactions were observed to follow first order kinetics,
      with an activation energy of approximately 420 kJ mol(-1). Time-dependent
      membrane disruption was also observed for the interaction with CPZ, such that
      holes appeared in the phospholipid bilayer after the interaction of CPZ. For this
      process of membrane disruption, "lag-burst" kinetics was demonstrated.

PMID- 19093752
TI  - Transduction mechanism of carbon nanotubes in solid-contact ion-selective
      electrodes.
AB  - Porous carbon materials and carbon nanotubes were recently used as solid contacts
      in ion-selective electrodes (ISE), and the signal transduction mechanism of these
      carbon-based materials is therefore of great interest. In this work the ion-to
      electron transduction mechanism of carbon nanotubes is studied by using
      electrochemical impedance spectroscopy (EIS) and cyclic voltammetry (CV). Single
      walled carbon nanotubes (SWCNT) are deposited on glassy carbon (GC) disk
      electrodes by repetitive spraying, resulting in SWCNT layers with thicknesses of
      10, 35, and 50 mum. The impedance spectra of these GC/SWCNT electrodes in contact
      with aqueous electrolyte solution show a very small resistance and a large bulk
      capacitance that is related to a large effective double layer at the
      SWCNT/electrolyte interface. Interestingly, the impedance response of GC/SWCNT is
      very similar to that of poly(3,4-ethylenedioxythiophene) (PEDOT) film electrodes
      studied earlier under the same experimental conditions. The same equivalent
      circuit is valid for both types of materials. The reason is that both materials
      can be described schematically as an asymmetric capacitor where one side is
      formed by electronic charge (electrons/holes) in the SWCNT wall or along the
      conjugated polymer chain of PEDOT and the other side is formed by ions
      (anions/cations) in the solution (or in the ion-selective membrane when used as a
      solid contact in ISE).

PMID- 19093751
TI  - Self-assembled films of hydrophobin proteins HFBI and HFBII studied in situ at
      the air/water interface.
AB  - Hydrophobins are a group of surface-active fungal proteins known to adsorb to the
      air/water interface and self-assemble into highly crystalline films. We
      characterized the self-assembled protein films of two hydrophobins, HFBI and
      HFBII from Trichoderma reesei, directly at the air/water interface using Brewster
      angle microscopy, grazing-incidence X-ray diffraction, and reflectivity. Already
      in zero surface pressure, HFBI and HFBII self-assembled into micrometer-sized
      rafts containing hexagonally ordered two-dimensional crystallites with lattice
      constants of 55 A and 56 A, respectively. Increasing the pressure did not change
      the ordering of the proteins in the crystallites. According to the reflectivity
      measurements, the thicknesses of the hydrophobin films were 28 A (HFBI) and 24 A
      (HFBII) at 20 mN/m. The stable films could also be transferred to a silicon
      substrate. Modeling of the diffraction data indicated that both hydrophobin films
      contained six molecules in the unit cell, but the ordering of the molecules was
      somewhat different for HFBI and HFBII, suggesting specific protein-protein
      interactions.

PMID- 19093754
TI  - Conductive polyaniline/surfactant ion complex Langmuir-Blodgett films.
AB  - Organic-solvent-soluble amphiphilic polyanilne was prepared by ion complex
      formation of protonated polyaniline (PANI) and anionic surfactant
      dodecylbenzenesulfonic acid (DBSA). The amphiphilic PANI/DBSA ion complex shows
      stable monolayer behavior at the air-water interface and formation of LB films on
      solid substrates. The cyclic voltammograms for the monolayer PANI/DBSA LB films
      show two distinct redox process waves, that is, the quasi-reversible redox wave
      at around 0.05 V vs SCE as a lucoemeralidine/emeraldine couple and the symmetric
      surface wave behavior of PANI at 0.75 V vs SCE as an emeraldine/pernigraniline
      couple. The surface morphology of the monolayer PANI/DBSA LB film on a Si wafer
      shows that monolayer surface roughness is smooth at a molecular level with
      fiberlike bundle structures where the elongated main chains of polyanilines were
      assembled by pi-pi interaction of the polyanilines. Conductivity of PANI/DBSA LB
      films depends on the number of layers at less than four layers, and it becomes
      similar to the bulk conductivity, 0.5 S/cm, at more than four layers.

PMID- 19093755
TI  - Continuous on-site label-free ATP fluorometric assay based on aggregation-induced
      emission of silole.
AB  - In this letter, we have described the establishment of a label-free fluorometric
      assay to detect adenosine triphosphate (ATP), which can enable the monitoring of
      the ATP hydrolysis process continuously and in situ. This assay is based on a
      silole derivative with positively charged modifications, compound 1, that can
      aggregate on the negative charged ATP template through charge-charge interaction.
      Because the silole group has strong aggregation-induced fluorescence emission
      (AIE), we have found that the aggregation could induce strong fluorescence
      emission and its intensity is positively and linearly related to the ATP
      concentration. Meanwhile, 1 also shows good discrimination for ATP, where its
      hydrolysis products ADP, AMP, and adenosine could not induce sufficient
      aggregation to produce a strong fluorescence signal. These characteristics are
      sufficient to build up a sensitive fluorescence assay to monitor the ATP
      concentration change in solution in situ, and we have also verified its usability
      in studying the reaction process of phosphatase.

PMID- 19093756
TI  - Electron resist behavior of Pd hexadecanethiolate examined using X-ray
      photoelectron spectroscopy with nanometric lateral resolution.
AB  - Electron resist behavior of Pd hexadecanethiolate is studied by varying the e
      dosage from 2-280 muC.cm(-2). The e-beam exposed resist is characterized using
      energy dispersive spectroscopy, infrared spectroscopy, and X-ray photoelectron
      spectroscopy with nanometric lateral resolution. Electron beam exposure causes
      defects in the alkyl chain of the thiolate, giving the required solubility
      contrast during the developing step, thus qualifying the precursor as an e-beam
      resist. On exposure to the e-beam, the reduction of Pd(2+) to Pd(0) is observed,
      and the reduction increases with increasing e-dosage. The resist is highly
      sensitive, with the estimated sensitivity being 32 muC.cm(-2). Thermolysis at 250
      degrees C leads to the formation of Pd nanoparticles, demonstrating the essential
      feature of a direct write resist for conducting patterns.

PMID- 19093757
TI  - Carbon-centered radicals in cigarette smoke: acyl and alkylaminocarbonyl
      radicals.
AB  - The widely accepted mechanism of formation for carbon-centered radicals in the
      gas-phase cigarette smoke involves reactions of NO(2) and alkadienes. However,
      specific examples of such radicals have never been isolated from fresh cigarette
      smoke or their structure determined. We have identified two previously
      unrecognized classes of carbon-centered radicals, alkylaminocarbonyl and acyl
      radicals, that are unrelated to radicals that form by NO(x) chemistry. The
      combined abundance of these mainstream smoke radicals is significantly higher
      than the alkyl radicals previously quantified by electron paramagnetic resonance
      (EPR) solution spin-trapping methods. The new radicals were trapped directly from
      smoke with either 3-amino-proxyl (3AP) or 3-cyano-proxyl radical on a solid
      support and identified by combination of chemical synthesis, deuterium labeling,
      high-resolution mass spectrometry, nuclear magnetic resonance (NMR) spectroscopy,
      and ab initio quantum mechanical calculations. 3AP-R adducts were quantified both
      by high-performance liquid chromatography tandem mass spectrometry (HPLC-MS/MS)
      and by high-performance liquid chromatography with fluorescence detection
      (HPLC/FLD). Seven acyl and 11 alkylaminocarbonyl radicals were identified in the
      whole smoke of cigarettes made from single tobacco varieties and blended tobacco
      research cigarettes. The overall yield of these radicals was measured to be 168
      245 nmol/cigarette from machine-smoked cigarettes under Federal Trade Commission
      (FTC) conditions. The yield was significantly reduced when the gas-phase smoke
      was separated from whole smoke by filtration through a 0.1 microm Cambridge
      filter pad or upon aging whole smoke in an inert tube.

PMID- 19093758
TI  - Fluorescence correlation spectroscopy: criteria for analysis in complex systems.
AB  - We have evaluated the effect of varying three key parameters for Fluorescence
      Correlation Spectroscopy analysis, first in the context of a one species/one
      environment system, and then in a complex system composed of two species, or
      conversely, two environments. We establish experimentally appropriate settings
      for the (1) minimum lag time, (2) maximum lag time, and (3) averaging times over
      which an autocorrelation is carried out, as a function of expected diffusion
      decay time for a particular solute, and show that use of appropriate settings
      plays a critical role in recovering accurate and reliable decay times and
      resulting diffusion constants. Both experimental and simulated data were used to
      show that for a complex binary system, to extract accurate diffusion constants
      for both species, decay times must be bounded by adequate minimum and maximum lag
      times as dictated by the fast and slow diffusing species, respectively. We also
      demonstrate that even when constraints on experimental conditions do not permit
      achieving the necessary lag time limits for both of the species in a binary
      system, the accuracy of the recovered diffusion constant for the one species
      whose autocorrelation function is fully time-resolved is unaffected by
      uncertainty in fitting introduced by the presence of the second species.

PMID- 19093759
TI  - Cracking in soft-hard latex blends: theory and experiments.
AB  - Volatile organic compounds (VOCs) in the traditional paint and coating
      formulations are an important health and environmental concern, and current
      formulations are increasingly moving toward water-based dispersions. However,
      even within the water-based systems, small quantities of organic solvents are
      used to promote particle coalescence. One route to achieving this goal has been
      to use mixtures of soft and hard particles, also known as latex blends. We
      investigate the drying of colloidal films containing mixtures of silica and
      acrylic particles. Since both the particles deform only slightly at room
      temperature, this work investigates the cracking behavior of films containing
      elastic particles of two different elastic moduli. We extend an existing model
      for the stress versus strain relation for identical particles in a colloidal film
      to that containing a mixture of equal-sized hard and soft elastic spheres while
      accounting for the nonaffine deformation. A transition from soft to rigidlike
      behavior is observed beyond a critical hard particle volume fraction ratio that
      matches with published results obtained from computer simulations. The model
      predictions are validated with extensive experimental data on the critical stress
      and critical cracking thickness for various ratios of hard and soft particle
      volume fraction.

PMID- 19093760
TI  - Optimization of a reusable, DNA pseudoknot-based electrochemical sensor for
      sequence-specific DNA detection in blood serum.
AB  - We describe in detail a new electrochemical DNA (E-DNA) sensing platform based on
      target-induced conformation changes in an electrode-bound DNA pseudoknot. The
      pseudoknot, a DNA structure containing two stem-loops in which the first stem's
      loop forms part of the second stem, is modified with a methylene blue redox tag
      at its 3' terminus and covalently attached to a gold electrode via the 5'
      terminus. In the absence of a target, the structure of the pseudoknot probe
      minimizes collisions between the redox tag and the electrode, thus reducing
      faradaic current. Target binding disrupts the pseudoknot structure, liberating a
      flexible, single-stranded element that can strike the electrode and efficiently
      transfer electrons. In this article we report further characterization and
      optimization of this new E-DNA architecture. We find that optimal signaling is
      obtained at an intermediate probe density ( approximately 1.8 x 10(13)
      molecules/cm(2) apparent density), which presumably represents a balance between
      steric and electrostatic blocking at high probe densities and increased
      background currents arising from transfer from the pseudoknot probe at lower
      densities. We also find that optimal 3' stem length, which appears to be 7 base
      pairs, represents a balance between pseudoknot structural stability and target
      affinity. Finally, a 3' loop comprised of poly(A) exhibits better mismatch
      discrimination than the equivalent poly(T) loop, but at the cost of decreased
      gain. Optimization over this parameter space significantly improves the signaling
      of the pseudoknot-based E-DNA architecture, leading to the ability to sensitively
      and specifically detect DNA targets even when challenged in complex,
      multicomponent samples such as blood serum.

PMID- 19093761
TI  - Exfoliation properties of acid-activated montmorillonites and their resulting
      organoclays.
AB  - The intercalation process of acid-treated montmorillonite clays by a cationinc
      surfactant (decyltrimethylammonuium) from a hydroxide solution was affected by
      the temperature of acid activation. Although the cation exchange capacity of the
      treated clay at 90 degrees C (0.74 mequiv g(-1)) was lower compared to that
      treated at room temperature (0.84 mequiv g(-1)), the uptaken amount of the
      surfactant (1.24 mmol g(-1)) and thus the basal spacing (3.83 nm) were higher.
      These values depended on the initial loading concentrations. However, when the
      clay was treated at room temperature, the uptaken amounts of surfactant (0.81
      mmol g(-1)) and the basal spacing (2.20 nm) were lower. These values were
      independent of the initial loading concentration. The higher basal spacing (3.83
      nm) was also affected by the type of the exchange medium and the washing solution
      by a mixture of ethanolic solutions. The intercalation of the surfactants
      occurred in two different ways, and was related to exfoliation properties of the
      acid activated clays. The intercalated surfactant exhibited different
      conformations in the interlayer space and different thermal stability.

PMID- 19093762
TI  - Aggregation and its influence on macroscopic in-plane organization in thin films
      of electrostatically self-assembled perylene-diimide/polyelectrolyte nanofibers.
AB  - The influence of precursor aggregation on materials deposition efficiency, film
      morphology, and macroscopic in-plane organization is explored for
      electrostatically self-assembled perylene-diimide/polyelectrolyte (PDI/PE)
      composites. PDI/PE thin films are prepared from aqueous precursor solutions by
      sequential dip-coating methods. Three PDI dyes are employed to probe the
      influence of aggregation on electrostatic self-assembly (ESA) of the composites.
      These include a singly charged PDI, C(7)OPDI(+), and two doubly charged species,
      PDISO(3)(2-) and TAPDI(2+). Poly(diallyldimethylammonium) (PDDA(+)) chloride and
      sodium poly(acrylate) (PA(-)) are used as the PEs. UV-vis absorbance and
      fluorescence spectroscopies show that all three dyes are heavily aggregated in
      their respective aqueous solutions. Temperature-dependent fluorescence data and
      filtration studies show that C(7)OPDI(+) is most strongly associated and also
      forms the largest aggregates. Absorbance data obtained as a function of the
      number of deposition cycles employed in film preparation demonstrate that
      C(7)OPDI(+) is also most efficiently deposited. Atomic force microscopy (AFM)
      images show that all three PDI/PE films are comprised of similar serpentine
      nanofibers. Interestingly, bulk absorbance dichroism data and AFM images
      demonstrate that the C(7)OPDI(+)/PA(-) composites incorporate macroscopically
      oriented dye and aligned nanofibers. Dye and nanofiber alignment is found to be
      perpendicular and parallel, respectively, to the dipping direction. No such
      organization is observed for the other two composites. It is concluded that
      deposition is strongly influenced by the level of precursor aggregation and that
      macroscopic in-plane organization in the C(7)OPDI(+)/PA(-) composites results
      from flow-induced alignment of relatively large preformed C(7)OPDI(+) aggregates
      during deposition.

PMID- 19093764
TI  - Mucosal vaccination of the newborn: an unrealized opportunity.

PMID- 19093763
TI  - Maleimide immobilized on a PE surface: preparation, characterization and
      application as a free-radical photoinitiator.
AB  - Maleimide groups are synthesized on the surface of PE films by means of two
      different routes, from oxidized and anhydride-grafted PE films. Maleimide groups
      covalently bonded to the surface of PE film were used as photopolymerization
      initiators of acrylic acid (AA) and glycidyl methacrylate (GMA). The formation of
      poly (acrylic acid) (PAA) and poly (glycidyl methacrylate) (PGMA) covalently
      bonded to the modified PE film surface by the photopolymerization process was
      demonstrated by ATR-FTIR, gravimetry, and SEM results. The thickness of the
      polymer layers formed in the polymerization depends on the irradiation time. The
      PAA layer formed in the polymerization is thinner than 250 nm, whereas that of
      PGMA in some case is thicker than 3 mum.

PMID- 19093765
TI  - Role of injectable and oral polio vaccines in polio eradication.

PMID- 19093767
TI  - IMVAMUNE: modified vaccinia Ankara strain as an attenuated smallpox vaccine.
AB  - Smallpox vaccines based on replicating vaccinia virus are known to elicit rare
      yet serious adverse events, particularly in human populations with immune
      deficiency, atopic dermatitis and at the extremes of age. A vaccine that induces
      protective immune responses equivalent to first-generation smallpox vaccines
      while reducing the risk for severe adverse events is critical for a national
      stockpile of smallpox vaccines. Modified vaccinia Ankara (MVA) has been proposed
      as an immediate solution for vaccination of high-risk individuals. Bavarian
      Nordic's vaccine MVA-BN (IMVAMUNE) is a MVA strain that is replication
      incompetent in mammalian cell lines. IMVAMUNE has been administered to more than
      1900 human subjects to date, including high-risk populations (e.g., people
      diagnosed with atopic dermatitis or infected with HIV) in which standard
      replicating vaccines are contraindicated. We review the Phase I clinical trial
      safety profile and immune responses and compare them with other smallpox
      vaccines, including ACAM2000 and Dryvax.

PMID- 19093768
TI  - Recent advances in cancer immunotherapy with an emphasis on vaccines.
AB  - Recent Advances in Cancer Immunotherapy with an Emphasis on Vaccines was the
      first meeting organized by the European Society of Cancer Immunology and
      Immunotherapy and Progress in Vaccine against Cancer, in collaboration with the
      Institute of Biological Research and Biotechnology of the National Hellenic
      Research Foundation, in a joint effort towards the setting up of a new generation
      of cancer vaccines. The main topics of the meeting included: the role of the
      tumor microenvironment in protecting the tumor from immune attack; differences in
      immunotherapy outcome in hematological malignancies versus solid tumors;
      rationale of multi-epitope vaccines; Treg cell elimination/inactivation, tumor
      stroma destruction, angiogenesis inhibition and the potentiality of 'preventive'
      vaccination in breast, colon, prostate and ovarian cancer in the early stages and
      during the 'wait-and-see' period. The ninth Progress in Vaccines against Cancer
      meeting will be held in Sofia, Bulgaria, 8-10 October 2009, at the Hilton Hotel.

PMID- 19093769
TI  - Viral hepatitis and serotonin: altering cytotoxic T-lymphocyte function in the
      liver.
AB  - Evaluation of: Lang PA, Contaldo C, Georgiev P et al. Aggravation of viral
      hepatitis by platelet-derived serotonin. Nat. Med. 14(7), 756-761 (2008). The
      study of host-virus interactions that determine liver disease pathogenesis and
      outcome of infection have been key issues of interest in the field of viral
      hepatitis. It is generally accepted that infection with noncytopathic viruses,
      such as HBV and HCV, triggers the activation of immunological events involving
      virus-specific cytotoxic T lymphocytes (CTLs), which helps to control viral
      replication but at the same time causes liver inflammation and damage due to the
      recruitment of antigen-nonspecific inflammatory cells. However, not much is known
      regarding the factors modulating intrahepatic CTL function or the complex
      interactions in the liver microenvironment that leads to liver immunopathology.
      The paper under evaluation here introduces the concept that platelet-derived
      serotonin supports virus persistence in the liver and aggravates CTL-mediated
      liver immunopathology.

PMID- 19093771
TI  - Oral polio vaccines and their role in polio eradication in India.
AB  - Although the oral polio vaccine has reduced the incidence of polio in India, the
      current polio scenario indicates that oral polio vaccine cannot eradicate polio
      from Uttar Pradesh and Bihar, two states that have approximately 32% of the total
      Indian population and report more than 96% of polio cases that occur in India.
      Poor response to oral polio vaccine by some children from these two states could
      be due to genetic factors. Thus, for polio eradication in India, inactivated
      polio vaccine is needed.

PMID- 19093772
TI  - Future of idiotypic vaccination for B-cell lymphoma.
AB  - During the last three decades, idiotypic vaccination has cleared all the hurdles
      between preclinical studies and randomized clinical trials, assuming the
      forerunner role among human therapeutic cancer vaccines. However, over the last
      few months, the very same Phase III clinical trials that were supposed to
      consecrate idiotype vaccines as the first such products to reach the market have,
      one after another, begun failing to achieve their main end points. While their
      negative outcome had been predicted long ago, it must be underlined that most
      clinical studies on idiotypic vaccination have shown a substantial correlation
      between induction of an idiotype-specific immune response and improvement of
      clinical outcome. Failures of late-stage clinical trials were due to severe
      pitfalls in their study design and not necessarily to idiotypic vaccination
      itself. Therefore, it is desirable that dedicated scientists and clinicians
      persevere until confirming ultimately the clinical benefit of a broadly and
      readily available idiotype vaccine.

PMID- 19093773
TI  - Randomized clinical studies of anti-tumor vaccination: state of the art in 2008.
AB  - This review elucidates state-of-the-art clinical studies on active specific
      immunotherapy with tumor vaccines. It refers solely to randomized studies and has
      a special focus on patient's survival, the most important parameter for any
      therapy. Of special interest, from a tumor immunological point of view, is a
      comparison between the results obtained with allogeneic tumor cell-derived
      vaccines and those obtained with autologous tumor cell-derived vaccines. Overall,
      autologous vaccines have given better results than allogeneic vaccines. Random
      mutations in cancer generate unique antigens in each individual case. The
      superiority of autologous vaccines suggests that unique tumor-associated antigens
      are particularly important in generating responsive T cells for a therapeutic
      effect.

PMID- 19093774
TI  - Recent approaches in hantavirus vaccine development.
AB  - Rodent-borne hantaviruses are associated with two main clinical disorders in
      humans: hemorrhagic fever with renal syndrome and hantavirus cardiopulmonary
      syndrome. Although hantavirus diseases can be life threatening and numerous
      research efforts are focused on the development of hantavirus prevention, no
      specific antiviral therapy is yet available and, at this time, no WHO-approved
      vaccine has gained widespread acceptance. This review will summarize the current
      knowledge and recent progress as well as new speculative approaches in the
      development of hantavirus vaccines.

PMID- 19093775
TI  - Current progress with Moraxella catarrhalis antigens as vaccine candidates.
AB  - The success of the immunization programs against Haemophilus influenzae type b
      and, more recently, Streptococcus pneumoniae in developed and some developing
      countries has demonstrated that invasive disease caused by these bacteria can be
      very effectively controlled by vaccination. There is also evidence that
      pneumococcal vaccines can reduce the incidence of acute otitis media in children.
      More complete control of this disease would be achieved if infections caused by
      Moraxella catarrhalis and nontypeable H. influenzae, the other common agents of
      otitis media in children and of a number of respiratory-associated infections in
      both children and adults, could also be controlled. Since these bacteria do not
      possess capsules and are not known to secrete exotoxins, the search for vaccine
      candidates has focused on the conserved epitopes exposed on the bacterial outer
      membrane. In this article, we review the contribution of M. catarrhalis to
      disease and recent advances in the development and testing of various vaccine
      candidates against this bacterium, including those still in the development stage
      and those approaching clinical trials. Recommendations are proposed for
      approaches needed for the standardization of assays and use of appropriate animal
      models for quality-control testing of these vaccine candidates. Regulatory issues
      surrounding vaccines of this type are also discussed.

PMID- 19093776
TI  - Haemophilus influenzae type b vaccine impact in resource-poor settings in Asia
      and Africa.
AB  - The Haemophilus influenzae type b (Hib) conjugate vaccine has been administered
      for almost 20 years in developed countries with remarkable success. More
      recently, the vaccine has been introduced in resource-poor settings, mainly those
      in Africa. African countries have documented large declines in Hib-invasive
      disease following universal vaccine introduction based on evaluation of routine
      surveillance data. As of 2007, only Mongolia in Asia had introduced the vaccine.
      Consequently, studies are limited to clinical trials in Bangladesh and Indonesia,
      and these also demonstrate substantial vaccine impact. Beyond invasive disease,
      three pivotal trials in Africa and Asia have demonstrated vaccine impact against
      clinical pneumonia end points. In all settings evaluated, Hib vaccine was shown
      to be cost effective, although the vaccine is not yet cost saving based on
      pentavalent vaccine prices in excess of US$3 per dose. Future issues include
      monitoring for serotype replacement and the effects of the HIV epidemic,
      evaluating the usefulness of a booster dose or new vaccine schedules and working
      to lower vaccine prices.

PMID- 19093777
TI  - Delivery systems: a vaccine strategy for overcoming mucosal tolerance?
AB  - Antigens administered via the oral and, to a lesser extent, the nasal route are
      potentially able to invoke tolerance, resulting in a nonreactive immune response.
      This has been a hurdle for mucosal vaccine development and yet the desire to
      induce protective local and systemic responses, with pain-free and more
      convenient products, has been the impetus driving mucosal vaccine R&D.
      Nevertheless, few mucosal vaccines have reached the marketplace and products are
      still treated with caution, particularly where live organisms are utilized. In
      this review, we examine the use of delivery systems with adjuvant properties as
      key components in a vaccine strategy that does not require the use of live
      vectors to overcome tolerance and have exemplified their success in mucosal
      vaccines, concentrating on the nasal and oral routes of administration.

PMID- 19093780
TI  - Selective sensing of anions with calix[4]pyrroles strapped with chromogenic
      dipyrrolylquinoxalines.
AB  - New calix[4]pyrroles bearing dipyrrolylquinoxaline as strapping elements have
      been synthesized and characterized by spectroscopic means. The binding behavior
      of these receptors at 25 degrees C was investigated first by proton NMR
      spectroscopy in CD(3)CN/DMSO-d(6) (9:1 v/v), as well as by UV-vis spectroscopy
      and isothermal titration calorimetry (ITC) in CH(3)CN/DMSO (97:3 v/v). The
      receptors displayed a selective colorimetric response when exposed to the
      fluoride, dihydrogen phosphate, and acetate anions (studied in the form of the
      corresponding tetrabutylammonium salts) and an enhanced affinity as compared to a
      comparable calix[4]pyrrole system lacking the dipyrrolylquinoxaline-containing
      strap.

PMID- 19093778
TI  - Use of humanized severe combined immunodeficient mice for human vaccine
      development.
AB  - The severe combined immunodeficient (SCID) mouse has no adaptive immunity,
      lacking mature T and B cells in the peripheral blood or the lymphoid organs. It
      has been used extensively in biomedical research as a valuable translational
      model for xeno-engraftment of human tissues and cells. This review focuses on the
      engraftment of human peripheral blood cells and tissues in SCID mice, as well as
      in the newly established and more permissive SCID mice deficient in the IL-2
      receptor gamma-chain. Human immune responses could be elicited and assessed in
      these humanized SCID mice upon vaccination or sensitization with allogeneic
      tissues. A translational model is proposed to attain preclinical data for testing
      human vaccines.

PMID- 19093781
TI  - Direct CNS delivery of siRNA mediates robust silencing in oligodendrocytes.
AB  - The most significant challenge remaining in the development of small interfering
      RNAs (siRNAs) as a new class of therapeutic drugs is successful delivery in vivo.
      The majority of reported studies describing delivery of siRNA or short hairpin
      RNA (shRNA) to the central nervous system (CNS) have focused on RNA interference
      (RNAi) in neurons. Here we show direct CNS delivery of siRNA to a different cell
      type-oligodendrocytes-using convection-enhanced delivery, and demonstrate robust
      silencing of an endogenous oligodendrocyte-specific gene, 2',3'-cyclic nucleotide
      3'-phosphodiesterase (CNPase) with siRNA formulated in saline. The silencing is
      not sequence-dependent as several different siRNAs are effective in inhibiting
      target gene expression. Furthermore, we show that CNPase mRNA reduction is dose
      dependent, durable for up to 1 week, and mediated by an RNAi mechanism.
      Increasing the flow rate of siRNA infusion increased the distribution of mRNA
      suppression to encompass white matter regions distant from the infusion site.
      Finally, we demonstrate suppression of CNPase mRNA in the nonhuman primate CNS.
      Taken together, these results show for the first time robust RNAi within
      oligodendrocytes in vivo and demonstrate the important potential of siRNAs in the
      treatment of CNS disorders involving oligodendrocyte pathology.

PMID- 19093782
TI  - In honor of Judah Folkman, M.D.

PMID- 19093784
TI  - Lymphatic endothelial cells, lymphedematous lymphangiogenesis, and molecular
      control of edema formation.
AB  - Lymphedema, defined as the abnormal accumulation of protein-rich fluid in soft
      tissues, results from the dysfunction of lymphatic system, an imbalance between
      lymph formation and its absorption into the initial lymphatics. Primary
      lymphedema occurs rarely on idiopathic or developmental abnormalities, especially
      hypoplasia or aplasia of lymphatics. Secondary lymphedema commonly develops when
      lymph transport is impaired due to lymphatic damage or resection of lymph nodes
      in surgery, infection, and radiation. Lymphatic endothelial cells (LECs) actively
      participate in the phenotypic consequences of a deranged lymphangiogenesis
      relating to tissue fluid accumulation in the pathogenesis of lymphedema. Recent
      insights into molecular genetic bases have shown an updated genotype-phenotype
      correlation between lymphangiogenesis, lymphatic function, and lymphedema. FOXC2,
      EphrinB2, VEGFR-3, VEGF-C, angiopoietin-2, Prox-1 and podoplanin have proved to
      be important factors of the genetic cascade linking to hereditary lymphedema, and
      embryonic and postnatal lymphatic development. FOXC2 may have a key role in
      regulating interactions between LECs and smooth muscle cells, and in the
      morphogenesis of lymphatic valves. Reduced VEGFR-3 tyrosine kinase activity and
      subsequent failure in transducing sufficient physiological VEGF-C/-D signals may
      affect LEC function and structure in the intercellular junctions and peri
      lymphatic components. Identification of genetic markers in humans and animal
      models would facilitate the management of environmental factors influencing the
      expression and severity of lymphedema, and provide a basis for developing novel
      targeted therapies for the disease.

PMID- 19093785
TI  - Arterial regulators taken up by lymphatics.
AB  - We present three examples of key genes that function in arterial specification
      that have recently been implicated in lymphatic development; ephrinB2, FoxC2, and
      Notch. In arterial cell fate determination, Foxc2 regulates both Notch and Notch
      ligand expression. In turn, Notch signal activation in arteries drives expression
      of ephrinB2. It will be interesting to determine if the regulatory relationships
      between these pathways found in arterial development are relevant to
      understanding lymphatic development, that is, we ask whether arterial regulators
      are also key regulators of lymphatic development.

PMID- 19093786
TI  - Why and how do tumors stimulate lymphangiogenesis?
AB  - Accumulating evidence shows that a subset of solid tumors stimulates
      lymphangiogenesis, which mediates lymphatic metastasis. Unlike blood vessels,
      lymphatics do not provide oxygen and nutrients that are essential for tumor
      growth. Why then do tumors induce lymphatic vessel growth? Do lymphatics play an
      active role in promoting tumor growth? Is tumor lymphangiogenesis secondary to
      blood vessel angiogenesis? How do tumors induce lymphangiogenesis? This review
      article focuses on discussing these fundamental issues related to cancer
      metastasis.

PMID- 19093783
TI  - The lymphatic system in health and disease.
AB  - The lymphatic vascular system has an important role in the regulation of tissue
      pressure, immune surveillance and the absorption of dietary fat in the intestine.
      There is growing evidence that the lymphatic system also contributes to a number
      of diseases, such as lymphedema, cancer metastasis and different inflammatory
      disorders. The discovery of various molecular markers allowing the distinction of
      blood and lymphatic vessels, together with the availability of a increasing
      number of in vitro and in vivo models to study various aspects of lymphatic
      biology, has enabled tremendous progress in research into the development and
      function of the lymphatic system. This review discusses recent advances in our
      understanding of the embryonic development of the lymphatic vasculature, the
      molecular mechanisms mediating lymphangiogenesis in the adult, the role of
      lymphangiogenesis in chronic inflammation and lymphatic cancer metastasis, and
      the emerging importance of the lymphatic vasculature as a therapeutic target.

PMID- 19093787
TI  - Reversing cancer from inside and out: oncogene addiction, cellular senescence,
      and the angiogenic switch.
AB  - Cancer is largely caused by genetic events that result in the mutation of
      oncogenes or tumor suppressor genes, leading to cell autonomous proliferation and
      growth. The repair of these mutant gene products may be expected to subvert this
      neoplastic behavior. Indeed, oncogene inactivation can result in the elimination
      of all or almost all tumor cells by various mechanisms through the phenomena
      described as oncogene addiction. Recently, we have shown that oncogene addiction
      occurs through at least two broad classes of mechanisms: tumor cell intrinsic
      mechanisms of cellular senescence and apoptosis; and tumor cell extrinsic host
      dependent mechanisms that include the shut-down of angiogenesis. We have argued
      that the abatement of oncogenic activity within a cancer cell not only leads to
      the demise of a tumor from within but also through the instruction of the
      restoration of the microenvironment.

PMID- 19093789
TI  - From anti-angiogenesis to anti-lymphangiogenesis: emerging trends in cancer
      therapy.
AB  - The theory that angiogenesis could support tumor growth and therefore be a target
      for cancer therapy was explored in publications by Judah Folkman in the 1970s.
      This theory was then fostered by Folkman for over 2 decades until, via modern
      molecular and cell biology techniques, it was vindicated in animal tumor models,
      and subsequently with the successful clinical trials of a humanized monoclonal
      antibody which neutralizes vascular endothelial growth factor (VEGF). In the
      process of proving the "anti-angiogenesis" theory, researchers in vascular,
      cancer, and developmental biology have gained insight into how the vascular
      network operates at the molecular level. Following on from the wave of activity
      that accompanied the study of angiogenesis, some of the molecular mechanisms
      controlling the related process of lymphangiogenesis have now been identified.
      The growth of lymphatic vessels was found to be controlled by proteins related to
      VEGF, namely VEGF-C and VEGF-D, which are associated with a number of human tumor
      types. The experimental inhibition of this process in animal models has suggested
      that lymphangiogenic growth factors facilitate the metastatic spread of tumor
      cells via lymphatics. Unlike the anti-angiogenesis strategy, anti
      lymphangiogenesis is yet to be tested clinically; however, the notion that anti
      lymphangiogenesis may be beneficial for cancer therapy is supported by extensive
      data from animal models and clinicopatholgical data. History may show that anti
      angiogenesis provided the vantage point from which anti-lymphangiogenesis was
      seen as a viable concept for targeting tumors and other pathological conditions.

PMID- 19093788
TI  - Roles of integrins in tumor angiogenesis and lymphangiogenesis.
AB  - The lifelong dedication of Dr. Judah Folkman to understand how tumors co-opt
      vasculature to promote tumor growth and spread resulted in the development of an
      astounding body of knowledge and development of new clinical therapeutics for
      cancer. Angiogenesis is a critical point in the development and dissemination of
      most human tumors. Tumor-associated lymphangiogenesis also plays an important
      role in mediating tumor spread to lymph nodes. The molecular regulations of these
      processes are complex, and many key molecular families have been implicated in
      the regulation of angiogenesis and lymphangiogenesis. By regulating cell-cell and
      cell-matrix contacts, integrins participate in blood and lymphatic vessel growth
      by promoting endothelial cell migration and survival. Understanding the
      underlying mechanisms by which integrins promote tumor-associated blood and
      lymphatic vessel development might provide important modalities for the
      therapeutic intervention of metastatic spread. This review focuses on the role of
      integrins in angiogenesis and lymphangiogenesis. Integrins represent potential
      targets for pharmacological agents and open new avenues for the control of
      metastatic spread in the treatment of malignancies. This article is dedicated to
      the memory of Dr. Judah Folkman, an amazing and caring teacher, scientist,
      physician, and friend.

PMID- 19093791
TI  - Molecular targets for therapeutic lymphangiogenesis in lymphatic dysfunction and
      disease.
AB  - The convergence of multiple disciplines upon the study of the lymphatic
      vasculature has invigorated a renaissance of research, using powerful
      investigative tools and an exponential growth of interest in this historically
      underappreciated system. Fundamental discoveries in lymphatic development have
      yielded relevant animal models for vexing clinical diseases that suffer from
      nonexistent of minimally effective treatments. Inherited and acquired lymphedema
      represent the current crux of research efforts to identify potential molecular
      therapies born from these early discoveries. The importance of the lymphatic
      system is, however, not limited to lymphedema but encompasses a diverse spectrum
      of human disease including inflammation and cancer metastasis. As the lymphatic
      vasculature continues to benefit from fruits of biomedical investigation,
      translation of mechanistic insights into targeted, rationally-conceived
      therapeutics will be become a reality.

PMID- 19093790
TI  - Developmental angiogenesis of the central nervous system.
AB  - The vasculature of the central nervous system (CNS) is highly specialized with a
      blood-brain-barrier, reciprocal neuroepithelial-endothelial cell interactions and
      extensive pericyte coverage. Developmentally, numerous important signaling
      pathways participate in CNS angiogenesis to orchestrate the precise timing and
      spatial arrangement of the complex CNS vascular network. From a therapeutic
      standpoint, the CNS vasculature has attracted increased attention since many
      human ailments, such as stroke, retinopathy, cancer and autoimmune disease are
      intimately associated with the biology of CNS blood vessels. This review focuses
      on growth factor pathways that have been shown to be important in developmental
      CNS vascularization through studies of mouse genetic models and human diseases.

PMID- 19093792
TI  - Corneal (lymph)angiogenesis--from bedside to bench and back: a tribute to Judah
      Folkman.
AB  - The normal cornea, the transparent "windscreen" of the eye, is devoid of both
      blood and lymphatic vessels. Nevertheless, both hem- and lymphangiogenesis can
      occur in response to severe corneal inflammation and can lead to blindness. Judah
      Folkman and co-workers exceedingly used the normally avascular cornea as the in
      vivo model system to study the mechanisms of angiogenesis and to test activators
      and inhibitors of angiogenesis in the last 3 decades. Recently, the cornea also
      became a successful model to study especially inflammatory lymphangiogenesis. As
      the last step in the circle from bedside to bench and back, we now are seeing the
      first (usually off-label) use of specific novel angiogenesis inhibitors in the
      diseased and pathologically vascularized human cornea to treat sight-threatening
      corneal angiogenesis and to promote graft survival after corneal transplantation
      by inhibiting lymphangiogenesis.

PMID- 19093793
TI  - Judah Folkman's contribution to the inhibition of angiogenesis.

PMID- 19093794
TI  - Percutaneous sclerotherapy of lymphatic malformations with doxycycline.
AB  - BACKGROUND: Lymphatic malformations (LMs) can be effectively treated by
      percutaneous intralesional injection of a variety of sclerosant drugs. This study
      aims to evaluate the efficacy of doxycycline in the treatment of LMs. METHODS AND
      RESULTS: We reviewed the medical records of all patients with LMs who underwent
      sclerotherapy with doxycycline between January 1, 2003 and September 1, 2004 at
      Children's Hospital Boston. Follow-up imaging was performed to assess for change
      in lesion size. Surveys were sent to all study patients, to assess perceived
      improvements in symptoms and satisfaction with the results. Sixty sclerotherapy
      procedures were performed on 41 patients in the 20-month study period. The median
      age was 6.9 years (3 mo-31 y). The most common location was cervicofacial (66%),
      followed by truncal (19%) and extremity (15%). The most common lesion type was
      macrocystic (49%), followed by combined (44%) and microcystic (7%). The major and
      minor complication rates were 2% and 10%, respectively. The mean outcome score by
      imaging was 4.41/5 with a 95% CI of [4.13-4.68] corresponding to about an 83%
      reduction in lesion size, and by patient survey was 4.47/5 with a 95% CI of [4.15
      4.79] corresponding to between a good to complete response. Higher complication
      rates were associated with microcystic and combined lesions (p = 0.03), and
      greater doxycycline dose (p = 0.05). CONCLUSIONS: Doxycycline is a safe and
      effective sclerosant for LMs. Greater follow-up is necessary to quantify long
      term outcomes and assess the risks of lesion recurrence.

PMID- 19093799
TI  - LRF remembers advisor Judah Folkman--true visionary and pioneer.

PMID- 19093800
TI  - Inhibitors of the NF-kappaB activation pathway from Cryptocarya rugulosa.
AB  - The nuclear factor-kappaB (NF-kappaB) signaling pathway is constitutively active
      in many types of cancers and is a potential therapeutic target. Using a cell
      based assay for stability of inhibitor of kappa B (IkappaB), a critical regulator
      of NF-kappaB activity, we found that an organic solvent extract of the plant
      Cryptocarya rugulosa inhibited constitutive NF-kappaB activity in human lymphoma
      cell lines. The active components were identified as rugulactone, a new alpha
      pyrone (1), and the known cryptocaryone (2). Rugulactone was the more active
      compound, exhibiting up to 5-fold induction of IkappaB at 25 microg/mL; maximal
      activity was observed with 10 h exposure of test cells to 1 or 2.

PMID- 19093801
TI  - A revised, hazy methane greenhouse  for the Archean Earth.
AB  - Geological and biological evidence suggests that Earth was warm during most of
      its early history, despite the fainter young Sun. Upper bounds on the atmospheric
      CO2 concentration in the Late Archean/Paleoproterozoic (2.8-2.2 Ga) from paleosol
      data suggest that additional greenhouse gases must have been present.
      Methanogenic bacteria, which were arguably extant at that time, may have
      contributed to a high concentration of atmospheric CH4, and previous calculations
      had indicated that a CH4-CO2-H2O greenhouse could have produced warm Late Archean
      surface temperatures while still satisfying the paleosol constraints on pCO2.
      Here, we revisit this conclusion. Correction of an error in the CH4 absorption
      coefficients, combined with the predicted early onset of climatically cooling
      organic haze, suggest that the amount of greenhouse warming by CH4 was more
      limited and that pCO2 must therefore have been 0.03 bar, at or above the upper
      bound of the value obtained from paleosols. Enough warming from CH4 remained in
      the Archean, however, to explain why Earth's climate cooled and became glacial
      when atmospheric O2 levels rose in the Paleoproterozoic. Our new model also shows
      that greenhouse warming by higher hydrocarbon gases, especially ethane (C2H6),
      may have helped to keep the Late Archean Earth warm.

PMID- 19093802
TI  - A case for ancient springs in Arabia Terra, Mars.
AB  - Based on new image data from the High Resolution Imaging Science Experiment
      (HiRISE) on Mars Reconnaissance Orbiter (MRO), a case can be made that several
      structures in Vernal Crater, Arabia Terra are ancient springs. This
      interpretation is based on comprehensive geomorphologic analysis coupled with
      assessment of multiple hypotheses. The structures identified extend across
      several kilometers and are exceptional in that nothing with their detail and
      scale has been reported from Mars. The deposits are associated with an extensive
      fracture system that may have facilitated upward flow of warm fluids. Several
      additional spring-like features occur in Vernal Crater, and it is possible that
      these are part of a major province of spring activity. Since springs are
      environments where life could have evolved on Mars, where that life could have
      found refuge as the climate became colder and drier, and where signatures of that
      life may be preserved, Vernal Crater may be a site of major astrobiological
      importance.

PMID- 19093803
TI  - Stable preformed chiral palladium catalysts for the one-pot asymmetric reductive
      amination of ketones.
AB  - The application of air stable preformed [(R)-BINAP]PdBr2, [(S)-BINAP]PdBr2, [(R)
      Tol-BINAP]PdBr2, and [(S,S)-CHIRAPHOS]PdBr2 complexes in the one-pot asymmetric
      reductive amination of various carbonyl compounds, leading to chiral amines in
      very good yields with high enantioselectivities (<99% ee), is reported.

PMID- 19093804
TI  - Biodegradable polymeric fiber structures in tissue engineering.
AB  - Tissue engineering offers a promising new approach to create biological
      alternatives to repair or restore function of damaged or diseased tissues. To
      obtain three-dimensional tissue constructs, stem or progenitor cells must be
      combined with a highly porous three-dimensional scaffold, but many of the
      structures purposed for tissue engineering cannot meet all the criteria required
      by an adequate scaffold because of lack of mechanical strength and
      interconnectivity, as well as poor surface characteristics. Fiber-based
      structures represent a wide range of morphological and geometric possibilities
      that can be tailored for each specific tissue-engineering application. The
      present article overviews the research data on tissue-engineering therapies based
      on the use of biodegradable fiber architectures as a scaffold.

PMID- 19093805
TI  - A new efficient catalytic system for the chemoselective cobalt-catalyzed cross
      coupling of aryl Grignard reagents with primary and secondary alkyl bromides.
AB  - The cobalt-catalyzed alkylation of aromatic Grignard reagents is performed in
      good yields by using a new simple and efficient catalytic system: CoCl(2)/TMEDA
      (1:1). Primary and secondary cyclic or acyclic alkyl bromides were used
      successfully. The reaction is highly chemoselective since ester, amide, and keto
      groups are tolerated. The procedure is inexpensive and very easy to carry out on
      a larger scale.

PMID- 19093808
TI  - Acquiring intellectual skills.

PMID- 19093809
TI  - Catalytic enantioselective approach to the eudesmane sesquiterpenoids: total
      synthesis of (+)-carissone.
AB  - A catalytic enantioselective approach to the eudesmane sesquiterpenoids is
      reported. The strategic use of a palladium-catalyzed enantioselective alkylation
      of vinylogous ester substrates forged the C(10) all-carbon quaternary center.
      This key transformation enabled a diastereoselective olefin hydrogenation to
      create the syn stereochemistry at C(7). The devised synthetic strategy allowed
      for the preparation of the antibacterial agent (+)-carissone and a formal
      synthesis of the P/Q-type calcium channel blocker (-)-alpha-eudesmol.

PMID- 19093811
TI  - Parasite susceptibility to amphotericin B in failures of treatment for visceral
      leishmaniasis in patients coinfected with HIV type 1 and Leishmania infantum.
AB  - BACKGROUND: Visceral leishmaniasis (VL) is an opportunistic infection that can
      occur among patients infected with human immunodeficiency virus type 1 (HIV-1) in
      areas where both infections are endemic. Highly active antiretroviral therapy has
      decreased the incidence of VL in southern Europe among HIV-1-infected patients,
      but VL is still observed among patients with low CD4 cell counts, and most
      coinfected patients receiving highly active antiretroviral therapy experienced
      relapse, despite initial treatment with liposomal amphotericin B. METHODS:
      Through long-term monitoring of VL in 10 patients with HIV-1 infection and/or
      AIDS, we compared parasite strains derived from primary and secondary episodes of
      VL. All the patients have received many courses of amphotericin B treatment
      and/or prophylaxis. RESULTS: Through molecular techniques, we have shown that
      secondary episodes of VL can be attributable to relapse (7 of 10 episodes) or
      reinfection (3 of 10). We developed an assay to measure amphotericin B
      susceptibility and found no evidence of decreased susceptibility among strains
      isolated from patients, some of whom were infected with the same isolate for up
      to 10 years. CONCLUSIONS: This apparent absence of resistance, as determined by
      in vitro susceptibility testing, has important consequences and suggests that
      amphotericin B will remain a useful drug of choice against VL, even after
      repetitive treatments or prophylactic use.

PMID- 19093810
TI  - Contribution of immunological and virological factors to extremely severe primary
      HIV type 1 infection.
AB  - BACKGROUND: During acute human immunodeficiency virus (HIV) infection, high viral
      loads and the induction of host immune responses typically coincide with the
      onset of clinical symptoms. However, clinically severe presentations during acute
      HIV type 1 (HIV-1) infection, including AIDS-defining symptoms, are unusual.
      METHODS: Virus isolates were tested for clade, drug susceptibility, coreceptor
      use, and growth rate in 2 case reports of sexual transmission of HIV-1 infection.
      Human leukocyte antigen (HLA) genotype was determined, and HIV-1-specific
      cytotoxic T lymphocyte responses to an overlapping peptide set spanning the
      entire HIV clade A and clade B proteome were assayed. RESULTS: The viruses
      isolated in the 2 unrelated case reports of severe primary HIV-1 infection showed
      R5/X4 dual-mixed tropism, belonged to clade B and CRF02-AG, and were highly
      replicative in peripheral blood mononuclear cell culture. Impaired humoral
      responses were paralleled by a profound absence of HIV-1-specific cytotoxic T
      lymphocyte responses to the entire viral proteome in the 2 case reports. In 1
      case report for which the virus source was available, there was a remarkable HLA
      similarity between the 2 patients involved in the transmission event, because 3
      of 4 HLA-A and HLA-B alleles had matched HLA supertype for both patients.
      CONCLUSIONS: The data suggest that concurrence of viral and host factors
      contributes to the clinical severity of primary HIV-1 infection and that patients
      infected with highly replicative, dual-tropic viruses are more prone to develop
      AIDS-defining symptoms during acute infection if they are unable to mount humoral
      and cellular HIV-1-specific immune responses. The presence of concordant HLA
      supertypes might facilitate the preferential transmission of HLA-adapted viral
      variants, further accelerating disease progression.

PMID- 19093812
TI  - Development of new semiconducting polymers for high performance solar cells.
AB  - A new low band gap semiconducting polymer, PTB1, was synthesized and found
      promising for solar energy harvesting. Simple polymer solar cells based on PTB1
      and methanofullerene [6,6]-phenyl-C(71)-butyric acid methyl esters (PC(71)BM)
      exhibit a solar conversion efficiency of 5.6%. An external quantum efficiency of
      67% and fill-factor of 65% are achieved, both of which are among the highest
      values reported for a solar cell system based on a low band gap polymer.

PMID- 19093813
TI  - Chlorine photoelimination from a diplatinum core: circumventing the back
      reaction.
AB  - The d(9)...d(9) Pt(2)(I,I)(tfepma)(2)Cl(2) (1) compound (tfepma =
      ((CF(3)CH(2)O)(2)P)(2)NCH(3)), d(7)-d(9) Pt(2)(I,III)(tfepma)(2)Cl(4) (2) and
      d(7)-d(7) Pt(2)(III,III)(tfepma)(2)Cl(6) (3), homologous suite of compounds have
      been prepared. Irradiation of 3 with visible light generates 2 in solution in the
      presence of 2,3-dimethyl-1,3-butadiene with a quantum efficiency of approximately
      38%. The evolution of Cl(2) upon solid-state photolysis of 3 represents the first
      example of the thermodynamically unfavorable halogen elimination without the use
      of a chemical trap.

PMID- 19093814
TI  - Axially chiral binaphthyl surrogates with an inner N-H-N hydrogen bond.
AB  - Novel chiral binaphtyl surrogates with an inner hydrogen bond have been created.
      The NH appears at 13.0-13.3 ppm in thier (1)H NMR spectrum, indicating extremely
      strong hydrogen bonding. Enantiomers of these compounds were stable at ambient
      temperature and separable by HPLC with a chiral stationary phase. The half-lives
      of racemization of the enantiomer are in the range 3 months to 2 years at 20
      degrees C, and the barriers for racemization are in the range 27.0 to 28.2
      kcal/mol. An X-ray crystal analysis of the compound (R = CHPh(2)) shows that the
      pseudonaphthyl skeleton including CN...HN is almost completely planar and the
      dihedral angle between the pseudonaphthalene and naphthalene rings is 128 degrees
      .

PMID- 19093815
TI  - High-sensitivity aminoazobenzene chemisorbed monolayers for photoalignment of
      liquid crystals.
AB  - We describe a new type of optically controlled liquid crystal alignment layer
      that demonstrates unprecedented performance. It consists of an aminoazobenzene
      type material with a very simple molecular structure, which is derived from
      methyl red by a one-step synthesis. We have devised a method of forming
      covalently attached monolayers of this material on glass by an amine-assisted
      condensation reaction involving the triethoxysilane end of the molecule. A
      nematic liquid crystal (LC) cell made with the monolayer and a rubbed polymer
      layer was switched from a uniform state to a twisted state with a polarized 450
      nm control beam having a dose of 5.5 mJ/cm(2). This is equivalent to an average
      of only one absorbed photon per azobenzene group. Through atomic force
      microscopy, absorption spectroscopy, spectroscopic ellipsometry, and second
      harmonic generation experiments, we have confirmed that layers of this type are
      smooth and uniform with a surface coverage consistent with a monolayer and that
      the azobenzene groups are tilted, on average, 55 degrees with respect to the
      surface normal. These characteristics lead to a large interaction energy density
      between the layer and LC. The monolayer's rapid response in developing anisotropy
      in this property can be attributed to a large absorption cross section, as well
      as the favorable tilt angle, which allows for sufficient photoisomerization free
      volume in a dense layer.

PMID- 19093816
TI  - Application of the moving boundary truncation method to reactive scattering: H +
      H2, O + H2, O + HD.
AB  - The moving boundary truncation (MBT) method is a time-dependent adaptive method
      that can significantly reduce the number of grid points needed to perform
      accurate wave packet propagation while maintaining stability. This work presents
      a more robust variation of the method. Significant improvements have been made
      that allow the MBT method to be applied to any potential energy surface and used
      with any propagation method. The new variation of MBT is applied to the collinear
      H + H(2) reaction (using a LEPS potential) to demonstrate the stability and
      accuracy. Reaction probabilities are calculated for the three-dimensional
      nonrotating O((3)P) + H(2) and O((3)P) + HD reactions to demonstrate that the MBT
      can be used with a variety of numerical propagation techniques.

PMID- 19093817
TI  - Reversible exciplex formation followed charge separation.
AB  - The reversible exciplex formation followed by its decomposition into an ion pair
      is considered, taking into account the subsequent geminate and bulk ion
      recombination to the triplet and singlet products (in excited and ground states).
      The integral kinetic equations are derived for all state populations, assuming
      that the spin conversion is performed by the simplest incoherent (rate)
      mechanism. When the forward and backward electron transfer is in contact as well
      as all dissociation/association reactions of heavy particles, the kernels of
      integral equations are specified and expressed through numerous reaction
      constants and characteristics of encounter diffusion. The solutions of these
      equations are used to specify the quantum yields of the excited state and
      exciplex fluorescence induced by pulse or stationary pumping. In the former case,
      the yields of the free ions and triplet products are also found, while in the
      latter case their stationary concentrations are obtained.

PMID- 19093818
TI  - Determination of the rate constant for the NH2(X(2)B1) + NH2(X(2)B1) reaction at
      low pressure and 293 K.
AB  - The rate constant for the reaction NH(2)(X(2)B(1)) + NH(2)(X(2)B(1)) --> products
      was measured in CF(4), N(2) and Ar carrier gases at 293 +/- 2 K over a pressure
      range from 2 to 10 Torr. The NH(2) radical was produced by the 193 nm photolysis
      of NH(3) dilute in the carrier gas. Both the loss of NH(3) and its subsequent
      recovery and the production of NH(2) and subsequent reaction were monitored
      simultaneously following the photolysis laser pulse. Both species were detected
      using quantitative time-resolved high-resolution absorption spectroscopy. The
      NH(3) molecule was monitored in the NIR using a rotation transition of the nu(1)
      + nu(3) first combination band near 1500 nm, and the NH(2) radical was monitored
      using the (1)2(21) <-- (1)3(31) rotational transition of the (0,7,0)A(2)A(1) <--
      (0,0,0) X(2)B(1) band near 675 nm. The low-pressure rate constant showed a linear
      dependence on pressure. The slope of the pressure dependence was dominated by a
      recombination rate constant for NH(2) + NH(2) given by (8.0 +/- 0.5) x 10(-29),
      (5.7 +/- 0.7) x 10(-29), and (3.9 +/- 0.4) x 10(-29) cm(6) molecule(-2) s(-1) in
      CF(4), N(2), and Ar bath gases, respectively, where the uncertainties are +/
      2sigma in the scatter of the measurements. The average of the three independent
      measurements of the sum of the disproportionation rate constants (the zero
      pressure rate constant) was (3.4 +/- 6) x 10(-13) cm(3) molecule(-1) s(-1), where
      the uncertainty is +/-2sigma in the scatter of the measurements.

PMID- 19093819
TI  - Stoichiometric network analysis and associated dimensionless kinetic equations.
      Application to a model of the Bray-Liebhafsky reaction.
AB  - The stoichiometric network analysis (SNA) introduced by B. L. Clarke is applied
      to a simplified model of the complex oscillating Bray-Liebhafsky reaction under
      batch conditions, which was not examined by this method earlier. This powerful
      method for the analysis of steady-states stability is also used to transform the
      classical differential equations into dimensionless equations. This
      transformation is easy and leads to a form of the equations combining the
      advantages of classical dimensionless equations with the advantages of the SNA.
      The used dimensionless parameters have orders of magnitude given by the
      experimental information about concentrations and currents. This simplifies
      greatly the study of the slow manifold and shows which parameters are essential
      for controlling its shape and consequently have an important influence on the
      trajectories. The effectiveness of these equations is illustrated on two
      examples: the study of the bifurcations points and a simple sensitivity analysis,
      different from the classical one, more based on the chemistry of the studied
      system.

PMID- 19093820
TI  - Coherent anti-Stokes Raman scattering microscopy of samples probed with Gaussian
      volumes.
AB  - Coherent anti-Stokes Raman scattering (CARS) microscopy is becoming increasingly
      popular to characterize biochemical samples. Within this context, we show that
      theoretical analysis can still be accomplished under the simple assumption of
      Gaussian volumes instead of spatial shapes obtainable from diffraction necessary
      to describe the tight-focusing condition realized within the focus of microscopes
      with high numerical apertures. The assumption, common in other physical and
      chemical spectroscopic techniques based on microscopy (e.g., fluorescence
      correlation spectroscopy, photon counting histogram) and never applied to CARS,
      is here used to determine the expression of the anti-Stokes electric field.
      Contrary to the standard approach resorting to numerical methods, we find that
      either the field is analytical for certain shapes of the Raman scatterer or the
      numerical reconstruction is strongly limited. In addition, we examine tests
      against two typical problems found in the literature, namely, a description of
      CARS radiation patterns and CARS imaging. With regard to the latter, we remark
      that the loss of spatial symmetry, the treatment of which is onerous in standard
      CARS microscopy because of possible separations between the microscope focus and
      the Raman scatterer, can be handled with ease in the limit of Gaussian volumes.
      An example is considered for polystyrene beads that are usually employed as test
      model of a CARS response of relevant biochemical samples.

PMID- 19093821
TI  - Vibrational signature of the conformers in tyramine studied by IR dip and
      dispersed fluorescence spectroscopies.
AB  - Dispersed fluorescence and IR dip spectra of seven conformers of tyramine were
      measured in a supersonic jet. Observed vibrational bands are assigned based on
      quantum chemical calculations. The vibrational frequency of out-of-plane CH
      bending in the benzene ring shows characteristic shifts according to the
      conformation of C(beta)-C(alpha), while that of CH stretching in the methylene
      chain reflects the conformation of N-C(beta). From these vibrational frequencies,
      assignments of the conformers observed in the S(1)-S(0) laser induced
      fluorescence spectrum are discussed.

PMID- 19093822
TI  - Vibrational spectral diffusion in supercritical D2O from first principles: an
      interplay between the dynamics of hydrogen bonds, dangling OD groups, and
      inertial rotation.
AB  - We have presented a first principles theoretical study of vibrational spectral
      diffusion and underlying molecular dynamics in supercritical heavy water at three
      different densities ranging from 1.1 to 0.39 g cm(-3). Our calculations are based
      on ab initio molecular dynamics simulations for trajectory generation and wavelet
      analysis for frequency calculations, and no empirical potential parameters are
      involved in the present study. Calculations of OD frequency-distance (D...O)
      conditional probabilities reveal that the rate of increase of OD frequency with
      D...O distance gradually decreases with lowering of density. Also, the maximum
      probability moves to a higher frequency-larger D...O distance region with
      decreasing density due to weakening of hydrogen bonds and increased number of
      dangling OD bonds in these systems. The correlations between the stretch
      frequencies and the electric fields on D atoms (along OD bonds) are also
      calculated, and the magnitude of such correlations is found to be similar to
      those of frequency-distance (D...O) correlations for the present supercritical
      systems. The vibrational spectral diffusion in supercritical water shows two time
      scales: one around 100 fs or less and the other in the region of 150-600 fs with
      the shorter time scale carrying the larger weight. It is found that, unlike
      ambient water, for supercritical water the slower component of the spectral
      diffusion does not necessarily capture the hydrogen bond dynamics at all
      densities. Rather, an interplay between the dynamics of hydrogen bonds, dangling
      OD groups, and the inertial rotation of OD bonds determines the times scales of
      spectral diffusion in a rather subtle manner. While the slower component of
      spectral diffusion at high density is determined by the lifetimes of hydrogen
      bonds, it is the lifetime of dangling OD groups that decides the slower component
      at low density, and the reverse holds for the faster components. The fast
      inertial rotation also shows up as the faster component of spectral diffusion.
      Dynamical correlations between the relaxation of frequency fluctuations and that
      of electric field fluctuations are also explored. Our calculations of rotational
      dynamics show, unlike ambient water, no frequency dependence of the rotational
      relaxation of OD bonds because of faster interconversion of different hydrogen
      bonding states and a reduced role of the hydrogen bond strength as a significant
      determinant of rotational motion caused by higher thermal energy of supercritical
      states.

PMID- 19093823
TI  - Kinetics of the gas-phase reactions of OH and NO3 radicals and O3 with 1,4
      thioxane and 1,4-dithiane.
AB  - Rate constants for the gas-phase reactions of the cyclic organosulfur compounds
      1,4-thioxane and 1,4-dithiane with NO(3) radicals and O(3) have been measured at
      296 +/- 2 K, and rate constants for their reactions with OH radicals have been
      measured over the temperature range 278-350 K. Relative rate methods were used to
      measure rate constants for the OH radical and NO(3) radical reactions. The OH
      radical reaction in the presence of NO(x) and, to a lesser extent, the NO(3)
      radical reaction were subject to secondary reactions leading to additional
      removal of 1,4-thioxane and/or 1,4-dithiane. The rate constants obtained for the
      NO(3) radical and O(3) reactions at 296 +/- 2 K were (5.1 +/- 1.1) x 10(-14)
      cm(3) molecule(-1) s(-1) and <2 x 10(-19) cm(3) molecule(-1) s(-1), respectively,
      for 1,4-thioxane and (5.9 +/- 1.8) x 10(-14) cm(3) molecule(-1) s(-1) and <2.5 x
      10(-19) cm(3) molecule(-1) s(-1), respectively, for 1,4-dithiane. For the OH
      radical reactions, the temperature-dependent rate expressions obtained were k(OH
      + 1,4-thioxane) = 2.54 x 10(-12) e((619+/-51)/T) cm(3) molecule(-1) s(-1) (278
      349 K) and k(OH + 1,4-dithiane) = 3.71 x 10(-12) e((621+/-163)/T) cm(3) molecule(
      1) s(-1) (278-350 K), with 298 K rate constants of (2.03 +/- 0.41) x 10(-11)
      cm(3) molecule(-1) s(-1) for 1,4-thioxane and (2.98 +/- 0.75) x 10(-11) cm(3)
      molecule(-1) s(-1) for 1,4-dithiane. For the experimental conditions employed,
      aerosol formation from the OH radical-initiated reactions of both 1,4-thioxane
      and 1,4-dithiane was important, accounting for approximately 60% of the
      organosulfur compounds reacted in both the presence and absence of NO(x). The
      data obtained here for 1,4-thioxane and 1,4-dithiane are compared with literature
      data for the corresponding reactions of simple acyclic alkyl sulfides and ethers.

PMID- 19093824
TI  - Electric dipole (hyper)polarizabilities of selected X2Y2 and X3Y3 (X = Al, Ga, In
      and Y = P, As): III-V semiconductor clusters. An ab initio comparative study.
AB  - A systematic ab initio comparative study of the (hyper)polarizabilities of
      selected III-V stoichiometric semiconductor clusters has been carried out. Our
      investigation focuses on the ground state structures of the dimers and on two
      dissimilar trimer configurations of aluminum, gallium, indium phosphide and
      arsenide. The basis set effect on both the polarizabilities and
      hyperpolarizabilities of the studied systems has been explicitly taken into
      account relying on the augmented correlation consistent aug-cc-pVnZ (n = D, T, Q,
      and 5) basis sets series. In addition, a rough estimation of the effects of the
      relativistic effects on the investigated properties is provided by extension of
      the study to include calculations performed with relativistic electron core
      potentials (or pseudopotentials). Electron correlation effects have been
      estimated utilizing methods of increasing predictive reliability, e.g., the
      Moller-Plesset many body perturbation theory and the couple cluster approach. Our
      results reveal that in the considered semiconductor species the Group III
      elements (Al, Ga, In) play a vital role on the values of their relative
      (hyper)polarizability. At all levels of theory employed the most hyperpolarizable
      clusters are the indium derivatives while the aluminum arsenide clusters also
      exhibit high, comparable hyperpolarizabilities. The less hyperpolarizable species
      are those composed of gallium and this is associated with the strong influence of
      the nuclear charge on the valence electrons of Ga due to the poor shielding that
      is provided by the semicore d electrons. In addition, the analysis of the
      electronic structure and the hyperpolarizability magnitudes reveals that
      clusters, in which their bonding is characterized by strong electron transfer
      from the electropositive to the electronegative atoms, are less hyperpolarizable
      than species in which the corresponding electron transfer is weaker. Lastly, from
      the methodological point of view our results point out that the
      hyperpolarizabilities of those species converge when an augmented triple-zeta
      quality basis set is used and, also, that the second order Moller-Plesset
      approximation (MP2) overestimates considerably their second hyperpolarizabilities
      with respect to the highest level of coupled cluster theory applied in this study
      (CCSD(T)).

PMID- 19093825
TI  - Graphene terahertz generators for molecular circuits and sensors.
AB  - Using ab initio density functional theory methods, the optimized structure of the
      single-, double-, and triple-layered graphene nanoribbons with different stacking
      orders and edges is calculated along with their Raman spectrums. For each case
      studied, graphene is found to be a potential source of vibrational signals in the
      terahertz region of the spectrum when molecules or another layer are adsorbed in
      the surface; this effect is independent of the hydrogen presence at the edges,
      and the stacking order. The visible low-frequency modes increase with the
      addition of graphene layers, and the number of modes may be influenced by the
      type of edges. The monolayer shows better performance due to the lower number of
      vibrational modes. The nanoribbon with fewer modes at the terahertz range is used
      to show a potential application of graphene acting as a sensor of single
      molecules.

PMID- 19093826
TI  - Poly(N-isopropylacrylamide) thin films densely grafted onto gold surface:
      preparation, characterization, and dynamic AFM study of temperature-induced chain
      conformational changes.
AB  - Thermally responsive poly(N-isopropylacrylamide) (PNIPAM) films are attracting
      considerable attention since they offer the possibility to achieve reversible
      control over surface wettability and biocompatibility. In this paper, we first
      report a new and simple method for the grafting under melt of amine-terminated
      PNIPAM chains onto gold surfaces modified with a self-assembled monolayer (SAM)
      of reactive thiols. The formation of homogeneous tethered PNIPAM films, whose
      thickness can be tuned by adjusting polymer molecular weight or SAM reactivity,
      is evidenced by using the combination of ellipsometry, X-ray photon spectroscopy,
      infrared spectroscopy (PM-IRRAS), and atomic force microscopy. The calculation of
      grafting parameters from experimental measurements indicated the synthesis of
      densely grafted PNIPAM films and allowed us to predict a "brushlike" regime for
      the chains in good solvent. In a second part, the temperature-induced responsive
      properties are studied in situ by conducting dynamic AFM measurements using the
      amplitude modulation technique. Imaging in water environment first revealed the
      reversible modification of surface morphology below and above the theoretical
      lower critical solution temperature (LCST) of PNIPAM. Then, the determination of
      amplitude and phase approach curves at various temperatures provided direct
      measurement of the evolution of the damping factor, or similarly the dissipated
      energy, as a function of the probe indentation into the PNIPAM film. Most
      interestingly, we clearly showed the subtle and progressive thermally induced
      chain conformational change occurring at the scale of several nanometers around
      the expected LCST.

PMID- 19093827
TI  - Identification of a boron-containing intermediate in the boron tribromide
      mediated aryl propargyl ether cleavage reaction.
AB  - An alternate reaction mechanism for the boron tribromide mediated deprotection of
      aryl propargyl ethers based on the isolation of a key boron-containing byproduct
      is proposed. On the basis of the new mechanistic insight, we discovered that
      HBBr(2) x SMe(2) can also be used for cleaving aryl propargyl ethers.

PMID- 19093828
TI  - Copper-facilitated Suzuki reactions: application to 2-heterocyclic boronates.
AB  - The palladium-catalyzed Suzuki-Miyaura reaction has been utilized as one of the
      most powerful methods for C-C bond formation. However, Suzuki reactions of
      electron-deficient 2-heterocyclic boronates generally give low conversions and
      remain challenging. The successful copper(I) facilitated Suzuki coupling of 2
      heterocyclic boronates that is broad in scope is reported. Use of this
      methodology affords greatly enhanced yields of these notoriously difficult
      couplings. Furthermore, mechanistic investigations suggest a possible role of
      copper in the catalytic cycle.

PMID- 19093829
TI  - How accurate can a force field become? A polarizable multipole model combined
      with fragment-wise quantum-mechanical calculations.
AB  - A new method to accurately estimate the interaction energy between a large
      molecule and a smaller ligand is presented. The method approximates the
      electrostatic and induction contributions classically by multipole and
      polarizability expansions, but uses explicit quantum-mechanical fragment
      calculations for the remaining (nonclassical) contributions, mainly dispersion
      and exchange repulsion. Thus, it represents a limit of how accurate a force field
      can ever become for interaction energies if pairwise additivity of the
      nonclassical term is assumed (e.g., all general-purpose force fields). The
      accuracy is tested by considering protein-ligand model systems for which the true
      MP2/6-31G* interaction energies can be computed. The method is shown to be more
      accurate than related fragmentation approaches. The remaining error (2-5 and
      approximately10 kJ/mol for neutral and charged ligands, respectively) can be
      decreased by including the polarizing effect from surrounding fragments in the
      quantum-mechanical calculations.

PMID- 19093831
TI  - Discrete polyoxovanadate cluster into an organic free metal-oxide-based material:
      syntheses, crystal structures, and magnetic properties of a new series of
      lanthanide linked-POV compounds [{Ln(H2O)6}2As8V14O42(SO3)] x 8 H2O (Ln = La3+,
      Sm3+, and Ce3+).
AB  - This article describes the linking propensity of the sulfite encapsulated
      polyoxovanadate (POV) anion, [As(8)V(14)O(42)(SO(3))](6-), with aqua-lanthanide
      complex cations [Ln(H(2)O)(6)](3+) in a controlled wet synthesis resulting in a
      series of organic free metal-oxide-based materials
      [{Ln(H(2)O)(6)}(2)As(8)V(14)O(42)(SO(3))] x 8 H(2)O, Ln = La(3+) (1), Sm(3+) (2),
      and Ce(3+) (3). The title compounds have been characterized by elemental
      analyses, IR, diffuse reflectance, electron paramagnetic resonance, powder X-ray
      diffraction (XRD), thermogravimetric analysis (TGA), and single-crystal X-ray
      diffraction studies. All three compounds crystallize in the monoclinic space
      group P2(1)/n. Crystal data for 1: a = 13.4839(7), b = 12.3388(6), c =
      18.3572(10) A, beta = 108.2570 (10) degrees, V = 2900.4(3) A(3). Crystal data for
      2: a = 13.4156(3), b = 12.2588(3), c = 18.2501(4) A, beta = 108.049(3) degrees, V
      = 2853.8(10) A(3). Crystal data for 3: a = 13.4934(3), b = 12.3983(3), c =
      18.3992(4) A, beta = 108.025(3), V = 2927.0(10) A(3). Crystal structure shows
      that each cluster is surrounded by six [Ln(H(2)O)(6)](3+) complex cations, and
      each [Ln(H(2)O)(6)](3+) cation is coordinated to three surrounding POV cluster
      anions. The electron spin resonance spectra of compounds 1-3 show a typical
      single line (g = 1.9671 for 1, g = 1.9669 for 2, and g = 1.9704 for 3),
      characteristic for a V(4+) (d(4)) ion; in addition, a supplementary signal
      appears for compound 2 at g = 5.9238 due to the presence of the Sm(3+) (f(5))
      ion. All vanadium atoms exit in +4 oxidation states that have been confirmed by
      bond valence sum calculations. Variable-temperature magnetic studies for all
      three compounds 1-3 are performed and are discussed in terms of antiferromagnetic
      coupling interactions, giving importance to linking/assembling the {V(14)}
      cluster anions. TGA/mass analyses of compounds 1-3 (linked system) have been
      compared with that of the starting precursor [NH(4)](6)[As(8)V(14)O(42)(SO(3))]
      (discrete building unit). Interestingly, the evolution of SO(2) gas takes place
      for the discrete cluster compound [NH(4)](6)[As(8)V(14)O(42)(SO(3))] in a
      temperature range of 480-520 degrees C with the decomposition of the POV cluster
      anion, whereas the same evolution occurs at 520-580 degrees C for compounds 1-3.
      These comparative TGA/mass studies help to understand how the organic free linker
      elevates the thermal stability of the sulfite encapsulated POV cluster anion in
      going from a discrete cluster anion to the linked system (molecule to material).
      It has also been demonstrated that the stability of the sulfite anion increases
      to a greater extent when it is included in the cluster cage. The powder XRD
      studies of compounds 1-3 confirm that these are isostructural materials and
      provide information about the phase purity.

PMID- 19093832
TI  - Asymmetric 1,3-dipolar cycloaddition reactions of nitrile oxides catalyzed by
      chiral binaphthyldiimine-Ni(II) complexes.
AB  - Asymmetric cycloaddition reactions between several nitrile oxides and 3-(2
      alkenoyl)-2-oxazolidinones and 2-(2-alkenoyl)-3-pyrazolidinone derivatives were
      carried out in the presence of chiral binaphthyldiimine (BINIM)-Ni(II) complexes
      as catalysts. Using (R)-BINIM-4(3,5-xylyl)-2QN-Ni(II) complex (30 mol %), good
      regioselectivity (4-Me/5-Me = 85:15) along with high enantioselectivity (96% ee)
      of the 4-Me adduct were obtained for the reaction between isolable 2,4,6
      trimethylbenzonitrile oxide and 3-crotonoyl-5,5-dimethyl-2-oxazolidinone.
      Substituted and unsubstituted benzonitrile oxides and aliphatic nitrile oxides,
      which were generated from the corresponding hydroximoyl chloride in the presence
      of MS 4A, were reacted with 3-crotonoyl-5,5-dimethyl-2-oxazolidinone, 5,5
      dimethyl-3-(2-pentenoyl)-2-oxazolidinone, 5,5-dimethy-3-[3
      (ethoxycarbonyl)propenoyl]-2-oxazolidinone, 1-benzyl-2-crotonoyl-5,5-dimethyl-3
      pyrazolidinone, and 1-benzyl-2-[3-(ethoxycarbonyl)propenoyl]-5,5-dimethy-3
      pyrazolidinone in the presence of (R)-BINIM-4Ph-2QN-Ni(II) or (R)-BINIM-4(3,5
      xylyl)-2QN-Ni(II) complexes (10-30 mol %) as catalysts to give the corresponding
      cycloadducts in high yields, with high regioselectively (4-R/5-R = 85:15-99:1)
      and with moderate to high enantioselectivities (42-95% ee) of the 4-R adducts.
      Higher enantioselectivities and regioselectivities were obtained for the
      reactions using pyrazolidinone derivatives as the dipolarophiles. For the
      cycloadditions of 2-(2-alkenoyl)-1-benzyl-5,5-dimethyl-3-pyrazolidinones
      catalyzed by (R)-BINIM-4(3,5-xylyl)-2QN-Ni(II) complex (30 mol %), the
      enantioselectivity varied from 75% to 95% ee. The reactions between several
      nitrile oxides and 2-acryloyl-1-benzyl-5,5-dimethyl-3-pyrazolidinone in the
      presence of (R)-BINIM-4(3,5-xylyl)-2QN-Ni(II) complex (10 mol %) resulted in
      enantioselectivities (79-91% ee) that exceed those of previously reported
      enantioselective cycloadditions of acrylic acid derivatives. Furthermore, studies
      using a molecular modeling program using PM3 calculations were carried out to
      gain insight into the mechanisms of the asymmetric induction.

PMID- 19093830
TI  - Probing the specificity determinants of amino acid recognition by arginase.
AB  - Arginase is a binuclear manganese metalloenzyme that serves as a therapeutic
      target for the treatment of asthma, erectile dysfunction, and atherosclerosis. In
      order to better understand the molecular basis of inhibitor affinity, we have
      employed site-directed mutagenesis, enzyme kinetics, and X-ray crystallography to
      probe the molecular recognition of the amino acid moiety (i.e., the alpha-amino
      and alpha-carboxylate groups) of substrate l-arginine and inhibitors in the
      active site of arginase I. Specifically, we focus on (1) a water-mediated
      hydrogen bond between the substrate alpha-carboxylate and T135, (2) a direct
      hydrogen bond between the substrate alpha-carboxylate and N130, and (3) a direct
      charged hydrogen bond between the substrate alpha-amino group and D183. Amino
      acid substitutions for T135, N130, and D183 generally compromise substrate
      affinity as reflected by increased K(M) values but have less pronounced effects
      on catalytic function as reflected by minimal variations of k(cat). As with
      substrate K(M) values, inhibitor K(d) values increase for binding to enzyme
      mutants and suggest that the relative contribution of intermolecular interactions
      to amino acid affinity in the arginase active site is water-mediated hydrogen
      bond < direct hydrogen bond < direct charged hydrogen bond. Structural
      comparisons of arginase with the related binuclear manganese metalloenzymes
      agmatinase and proclavaminic acid amidinohydrolase suggest that the evolution of
      substrate recognition in the arginase fold occurs by mutation of residues
      contained in specificity loops flanking the mouth of the active site (especially
      loops 4 and 5), thereby allowing diverse guanidinium substrates to be
      accommodated for catalysis.

PMID- 19093833
TI  - Plasmon resonance energy transfer (PRET)-based molecular imaging of cytochrome c
      in living cells.
AB  - We describe the development of innovative plasmon resonance energy transfer
      (PRET)-based molecular imaging of biomolecules in living cells. Our strategy of
      in vivo PRET imaging relies on the resonant plasmonic energy transfer from a gold
      nanoplasmonic probe to conjugated target molecules, which creates "quantized
      quenching dips" within the Rayleigh scattering spectrum of the probe. The
      positions of these quantized quenching dips exactly match with the absorption
      peaks of the target molecule since we intentionally design nanoantennas (i.e.,
      nanoplasmonic probes) to overlap the electronic dipoles of the molecule and the
      plasmonic resonance dipole of nanoantennas. Such the quenching dips allow
      quantitative and long-term dynamic imaging of the target molecule without the
      drawbacks of photobleaching and blinking inherent to fluorescent markers, which
      cannot provide chemical fingerprints. Compared with other imaging methods, our
      PRET spectroscopic imaging method allows us to generate nanoscale specific
      wavelengths of local light sources in living systems via nanoantennas and
      transmit back the nanospectroscopic imaging data of biochemical activities in
      living cells. As a first demonstration of in vivo PRET imaging, we performed a
      visualization of the dynamics of intracellular cytochrome c in HepG2 cells under
      ethanol-induced apoptosis.

PMID- 19093834
TI  - Network dynamics and species exchange processes in aluminophosphate glasses: an
      in situ high temperature magic angle spinning NMR view.
AB  - In this contribution, we present an in situ high temperature 27Al and 31P magic
      angle spinning (MAS) NMR study of binary and ternary phosphate glasses at
      temperatures above the glass transition temperature TG. For binary phosphate
      glasses, xK2O-(1 - x)P2O5 and ternary aluminophosphate glasses 30K2O-xAl2O3-(70 
      x)P2O5 with 7 < x < 15 dynamic exchange processes between the various phosphate
      species (and aluminatespecies) present in the glasses could be identified in the
      temperature range between TG and the maximum achievable temperature Tmax of our
      high temperature MAS NMR setup, TG < T < Tmax. This observation indicates rapid P
      O-P and P-O-Al bond formation and bond breaking in the (alumino)phosphate
      glasses.From a modeling of the temperature dependence of these exchange
      processes, the activation energy EA for the corresponding process could be
      determined. These local bond breaking and making processes are ultimately linked
      to the macroscopic viscous flow and may indeed form the basic microscopic local
      step of viscous flow.

PMID- 19093836
TI  - Enantioselective total synthesis of (+)-cassiol.
AB  - An enantioselective total synthesis of (+)-cassiol is reported. The complex
      derived from Pd(2)(pmdba)(3) and enantiopure t-BuPHOX ligand catalyzes
      enantioconvergent decarboxylative alkylation to generate the quaternary carbon
      stereocenter at an early stage. The overall synthetic strategy involves a
      convergent late-stage coupling of two fragments. The synthesis features a longest
      linear sequence of eight steps.

PMID- 19093835
TI  - HIV fusion peptide and its cross-linked oligomers: efficient syntheses,
      significance of the trimer in fusion activity, correlation of beta strand
      conformation with membrane cholesterol, and proximity to lipid headgroups.
AB  - For enveloped viruses such as HIV, an approximately 20-residue N-terminal fusion
      peptide domain in the envelope protein binds to target cell membranes and plays a
      key role in fusion between the viral and cellular membranes during infection. The
      chemically synthesized HIV fusion peptide (HFP) catalyzes fusion between membrane
      vesicles and is a useful model system for understanding some aspects of HIV
      fusion. Previous studies have shown a common trimeric state for the envelope
      protein from several different viruses, including HIV, and in this study,
      practical high-yield syntheses are reported for HFP monomer (HFPmn) and
      chemically cross-linked HFP dimer (HFPdm), trimer (HFPtr), and tetramer (HFPte).
      The vesicle fusion rates per strand were ordered as follows: HFPmn < HFPdm <
      HFPtr approximately HFPte. This suggested that HFPtr is the smallest
      catalytically efficient oligomer. Solid-state NMR measurements of (13)CO chemical
      shifts were carried out in constructs labeled at either Ala-6 or Ala-15. For all
      constructs associated with cholesterol-containing membranes, the chemical shifts
      of both residues correlated with beta strand conformation while association with
      membranes without cholesterol resulted in a mixture of helical and beta strand
      conformations. The dependence of fusion rate on oligomer size is independent of
      membrane cholesterol content, so one interpretation of the data is fusion
      activity of both helical and beta strand conformations. Membrane location may be
      a determinant of fusion activity, and for all constructs in both conformations, a
      large fraction of the Ala-15 (13)CO groups were 5-6 A from the (31)P atoms in the
      lipid headgroups, while the Ala-6 (13)CO groups were more distant.

PMID- 19093837
TI  - A study of urea-dependent denaturation of beta-lactoglobulin by principal
      component analysis and two-dimensional correlation spectroscopy.
AB  - The water-urea-beta-lactoglobulin interaction was studied by means of principal
      component analysis (PCA) and two-dimensional correlation spectroscopy applied to
      the urea concentration-dependent FTIR spectra of aqueous urea-protein solutions.
      The two nu(CO) and nu(as)(CN) bands coming from urea's absorbance, instead of the
      amide bands arising from protein, were employed in the analysis. To get a precise
      view of the changes induced by the urea concentration-controlled unfolding
      process, the absorbance variations developed in the ternary water-urea-protein
      system were compared with those observed in a binary water-urea system [Y.M. Jung
      et al., J. Phys. Chem. B 2004, 108, 13008]. The comparative studies enabled to
      detect apparent differences between the absorbance changes caused solely by
      urea's concentration increase and by the urea-dependent unfolding process. Urea's
      ability to unfold protein was discussed in context of the indirect and the direct
      mechanism depending on urea's concentration. It was shown that both mechanisms
      are relevant, that is, the indirect for solutions below 3 M and the direct for
      solutions above 3 M concentration. The character of the mechanism is strictly
      correlated with the association level of urea molecules.

PMID- 19093839
TI  - Theoretical characterization of hydrogen polyoxides: HOOH, HOOOH, HOOOOH, and
      HOOO.
AB  - We have investigated the polyoxides HOOH, HOOOH, HOOOOH, and HOOO employing the
      CCSD(T) methodology, and the correlation consistent basis sets. For all
      molecules, we have computed fundamental vibrational frequencies, structural
      parameters, rotational constants, and rotation-vibration corrections. For HOOOH,
      we have obtained a good agreement between our results and microwave and infrared
      spectra measurements, although for the symmetric OO stretch some important
      differences were found. Heats of formation were computed using atomization
      energies, and our recommendation is as follows: DeltaH(o)(f,298)(HOOOH) = -21.50
      kcal/mol and DeltaH(o)(f,298)(HOOOOH) = -10.61 kcal/mol. In the case of HOOO, to
      estimate the heat of formation, we have constructed three isodesmic reactions to
      cancel high order correlation effects. The results obtained confirmed that the
      latter effects are very important for HOOO. The new DeltaH(o)(f,298)(HOOO)
      obtained is 5.5 kcal/mol. We have also calculated the zero-point energies of DO
      and DOOO to correct the experimental lower limit determined for the
      DeltaH(o)(f,298)(HOOO). The Delta(DeltaZPE) decreases the binding energy of HOOO
      by 0.56 kcal/mol. Employing the latter value, the new experimental lower limit
      for DeltaH(o)(f,298)(HOOO) is 3.07 kcal/mol, just 2.4 kcal/mol lower than our
      determination. We expect that the fundamental vibrational frequencies and
      rotational constants determined for HOOOOH and DOOOOD contribute to its
      identification in the gas phase. The vibrational spectrum of HOOOOH shows some
      overlapping with that of HOOOH thus indicating that one may encounter some
      difficulties in its characterization. We discuss the consequences of the
      thermochemical properties determined in this work, and suggest that the amount of
      HOOO present in the atmosphere is smaller than that proposed recently in this
      journal ( J. Phys. Chem A 2007, 111, 4727).

PMID- 19093838
TI  - Practical ruthenium-catalyzed cyclocarbonylation of allenyl alcohols in 2,4,6
      collidine leading to alpha,beta-unsaturated lactones: concise stereoselective
      synthesis of (+)-isomintlactone.
AB  - We have found that ruthenium-catalyzed cyclocarbonylation of allenyl alcohols in
      2,4,6-collidine under atmospheric pressure of carbon monoxide smoothly proceeds
      to afford alpha,beta-unsaturated five- and six-membered lactones in moderate to
      good yields. Furthermore, we have completed a highly stereoselective synthesis of
      (+)-isomintlactone by the cyclocarbonylation of allenyl alcohol using 2,4,6
      collidine.

PMID- 19093840
TI  - Stacking-faults-free zinc Blende GaAs nanowires.
AB  - Stacking-faults-free zinc blende GaAs nanowires have been grown by molecular beam
      epitaxy using the vapor-liquid-solid gold assisted growth method. Two different
      approaches were used to obtain continuous low supersaturation in the vicinity of
      the growing wires. A double distribution of gold droplets on the (111)B surface
      in the first case, and a highly terraced (311)B growth surface in the second case
      both avoided the commonly observed transition to wurtzite structure.

PMID- 19093841
TI  - Mechanism of very large scale assembly of SWNTs in template guided fluidic
      assembly process.
AB  - Very large scale patterned single-walled carbon nanotube (SWNT) networks were
      fabricated using a newly developed template guided fluidic assembly process. A
      mechanism for SWNT assembly and their control is described here. To maximize the
      directed assembly efficiency of SWNTs toward a wafer level SWNT deposition, Si or
      SiO(2) substrate was pretreated with precisely controlled SF(6), O(2), and Ar
      plasma. Chemical and physical properties of the surface were characterized using
      several surface characterization techniques to investigate and control the
      mechanism of SWNT assembly. We found that hydrophilic chemical groups such as
      hydroxides were created on the silicon or silicon oxide surface through the
      controlled plasma treatment and fluidic SWNT dip-coating process. Also we found
      that nanoscale rough surface structures formed during the plasma treatment
      significantly increased the number of dangling bonds and hydroxide functional
      groups on the surface. These combined chemical and physical enhancements that
      attract SWNTs in the aqueous solution enable us to build highly organized and
      very large scale SWNT network architectures effectively in various dimensions and
      geometries.

PMID- 19093842
TI  - Chirality-dependent transport properties of double-walled nanotubes measured in
      situ on their field-effect transistors.
AB  - Double-walled carbon nanotubes (DWNT), consisting of two coaxial tubes, is an
      ideal structure for chemical and physical applications. It is of essential
      importance to probe the one-to-one relationship between electrical transport and
      chiral structure of DWNTs. Here, the chirality-dependent transport properties of
      DWNTs have been systematically investigated in situ on their field-effect
      transistors, through building DWNT-based field-effect transistors into a
      transmission electron microscope. The transport characteristics of DWNTs can be
      directly correlated with their chiral indices, and the probe of inner tubes has
      also been achieved in situ.

PMID- 19093843
TI  - Hantupeptin A, a cytotoxic cyclic depsipeptide from a Singapore collection of
      Lyngbya majuscula.
AB  - Chemical investigation of the marine cyanobacterium Lyngbya majuscula from Pulau
      Hantu Besar, Singapore, has led to the isolation of a cyclodepsipeptide,
      hantupeptin A (1). The planar structure of 1 was assigned on the basis of
      extensive 1D and 2D NMR spectroscopic experiments. The absolute configuration of
      the amino and hydroxyl acid residues in the molecule was determined by
      application of the advanced Marfey method, chiral HPLC analysis, and Mosher's
      method. Hantupeptin A showed cytotoxicity to MOLT-4 leukemia cells and MCF-7
      breast cancer cells with IC(50) values of 32 and 4.0 microM, respectively.

PMID- 19093844
TI  - Catalytic asymmetric 1,3-dipolar cycloaddition of azomethine ylides with
      alpha,beta-unsaturated ketones.
AB  - Alpha,beta-unsaturated ketones are no longer the missing dipolarophiles in
      catalytic asymmetric 1,3-dipolar cycloaddition of azomethine ylides. In the
      presence of Cu(I)-Fesulphos complexes as catalysts (5 mol %), these substrates
      combine high reactivity, wide substitution tolerance, moderate to good endo/exo
      selectivities, and high enantiocontrol. The endo/exo-diastereoselectivity of the
      reaction is strongly dependent on the cis or trans nature of the enone moiety.

PMID- 19093845
TI  - Iron-catalyzed 1,4-addition of alpha-olefins to dienes.
AB  - A new intermolecular, stereo- and regioselective iron-catalyzed 1,4-addition of
      alpha-olefins to 1,3-dienes using as low as 1 mol % of an iminopyridine-ferrous
      chloride complex was developed. Importantly, both double bonds of the linear 1,4
      diene addition products are obtained with absolute stereocontrol.

PMID- 19093846
TI  - Isotope and phase effects on the proton tautomerism in polycrystalline porphycene
      revealed by NMR.
AB  - Using high resolution solid state (15)N and (2)H spectroscopy and longitudinal
      relaxometry we have studied the tautomerism of porphycene in the solid state,
      corresponding to a double proton transfer in two cooperative hydrogen bonds. The
      tautomerism is degenerate above 225 K but the degeneracy is lifted below this
      temperature, indicating a phase transition. Thus, the high-temperature phase is
      characterized by a dynamic proton disorder and the low-temperature phase by a
      dynamic proton order. (15)N magnetization transfer experiments obtained under
      cross polarization (CP) and magic angle spinning (MAS) conditions reveal the
      presence of two nonequivalent molecules A and B in the unit cell of phase II,
      exhibiting slightly different equilibrium constants of the tautomerism. Rate
      constants of the tautomerism in phase I could be obtained by the analysis of the
      longitudinal (15)N and (2)H relaxation times. The former, obtained at 9.12 MHz,
      exhibit a T(1) minimum around 270 K and are consistent with proton transfer
      induced dipolar (1)H-(15)N relaxation mechanism. The latter, obtained at 46.03
      MHz, exhibit a minimum around 330 K and arise from quadrupole relaxation. Within
      the margin of error, the rate constants of the HH and of the HD/DD tautomerism
      are the same, exhibiting a barrier of about 30 kJ mol(-1), as expected for an
      overbarrier reaction in a configuration with two compressed hydrogen bonds. By
      contrast, in the low-temperature phase a switch of the DD transfer kinetics into
      the nanosecond time scale is observed, exhibiting a non-Arrhenius temperature
      dependence which is typical for tunneling. This increase of the rate constants by
      lowering the temperature is discussed in terms of a switch from a concerted HH
      transfer in phase I to a stepwise transfer in phase II, where intermolecular
      interactions lower the energy of one of the cis-intermediates.

PMID- 19093847
TI  - All-trans-[ClRu(II)(py)4(NC)Ru(II)(py)4(CN)Ru(II)(py)4(NO)](PF6)4: a redox-active
      2-donor/1-acceptor system based on the electrophilic {RuNO}6 motif.
AB  - The new linear homotrinuclear compound trans
      [ClRu(II)(py)(4)(NC)Ru(II)(py)(4)(CN)Ru(II)(py)(4)(NO)](PF(6))(4) was prepared by
      reaction between the nitro complex trans
      [(NC)Ru(II)(py)(4)(CN)Ru(II)(py)(4)(NO(2))](+) and the solvento complex obtained
      by reaction between [ClRu(II)(py)(4)(NO)](3+) and N(3)(-) in acetone. The trans
      [ClRu(II)(py)(4) (NC)Ru(II)(py)(4)(CN)Ru(II)(py)(4)(NO)](4+) ion (I) has been
      characterized by (1)H NMR and IR spectroscopy (nu(NO) = 1919 cm(-1)). This
      species displays intense electronic absorptions in the visible region which can
      be assigned to donor-acceptor charge-transfer transitions (DACT) involving
      {RuNO}(6)-centered acceptor orbitals and donor orbitals located on the two
      different neighboring metal centers at ca. 6.7 and 12.6 A distance from the metal
      in the {RuNO}(6) fragment. Addition of OH(-) to I generated the nitro complex
      with a second-order rate constant of (12.5 +/- 0.2) x 10(3) M(-1) s(-1) (25
      degrees C). Cyclic voltammetry experiments complemented by
      spectroelectrochemistry in the UV-vis-NIR region reveal that I can be reversibly
      reduced at 0.49 or 0.20 V vs AgCl/Ag for acetonitrile and water, respectively,
      and oxidized at 0.71 or 0.57 V vs AgCl/Ag. The spectroscopic and
      spectroelectrochemical information (UV-vis-NIR, X-band EPR) supplemented with
      electronic structure computation (DFT) reveals that the one-electron reduction is
      centered on the nitrosyl moiety to yield a {RuNO}(7) species, while oxidation
      occurs on the chlororuthenium side of the molecule. Both processes yield
      significant changes of the electronic spectra which are discussed in parallel
      with the electronic structure picture as obtained by DFT.

PMID- 19093848
TI  - Bioactive pyridine-N-oxide disulfides from Allium stipitatum.
AB  - From Allium stipitatum, three pyridine-N-oxide alkaloids (1-3) possessing
      disulfide functional groups were isolated. The structures of these natural
      products were elucidated by spectroscopic means as 2-(methyldithio)pyridine-N
      oxide (1), 2-[(methylthiomethyl)dithio]pyridine-N-oxide (2), and 2,2'-dithio-bis
      pyridine-N-oxide (3). The proposed structure of 1 was confirmed by synthetic S
      methylthiolation of commercial 2-thiopyridine-N-oxide. Compounds 1 and 2 are new
      natural products, and 3 is reported for the first time from an Allium species.
      All compounds were evaluated for activity against fast-growing species of
      Mycobacterium, methicillin-resistant Staphylococcus aureus, and a multidrug
      resistant (MDR) variants of S. aureus. Compounds 1 and 2 exhibited minimum
      inhibitory concentrations (MICs) of 0.5-8 microg/mL against these strains. A
      small series of analogues of 1 were synthesized in an attempt to optimize
      antibacterial activity, although the natural product had the most potent in vitro
      activity. In a whole-cell assay at 30 microg/mL, 1 was shown to give complete
      inhibition of the incorporation of (14)C-labeled acetate into soluble fatty
      acids, indicating that it is potentially an inhibitor of fatty acid biosynthesis.
      In a human cancer cell line antiproliferative assay, 1 and 2 displayed IC(50)
      values ranging from 0.3 to 1.8 microM with a selectivity index of 2.3 when
      compared to a human somatic cell line. Compound 1 was evaluated in a microarray
      analysis that indicated a similar mode of action to menadione and 8-quinolinol by
      interfering with the thioredoxin system and up-regulating the production of
      various heat shock proteins. This compound was also assessed in a mouse model for
      in vivo toxicity.

PMID- 19093849
TI  - Lewis acidity enhancement of triarylboranes via peripheral decoration with
      cationic groups.
AB  - The cationic boranes [Ar(N+)BMes(2)](+), [Ar(N+)(2)BMes](2+), and
      [Ar(N+)(3)B](3+) (Ar(N+) = [4-(Me(3)N)-2,6-Me(2)-C(6)H(2)](+); Mes = mesityl)
      have been synthesized and studied by cyclic voltammetry. The results obtained in
      this study show that the reduction potential of these derivatives in THF is
      increased by 0.36 V upon each substitution of a mesityl by a cationic Ar(N+)
      anilium group. Remarkably, the trication [3](3+), whose triflate salt is water
      soluble, complexes cyanide anions in pure water at pH 7. These properties
      underscore the dramatic effects caused by the increased number of cationic
      groups.

PMID- 19093850
TI  - A [2 + 2 + 2]-cycloaddition approach toward 6-oxa-allocolchicinoids with
      apoptosis-inducing activity.
AB  - Following an A --> ABC strategy, a new synthesis of 6-oxa-allocolchicinoids was
      developed exploiting a microwave-promoted Co- or Rh-catalyzed intramolecular [2 +
      2 + 2]-cycloaddition (alkyne cyclotrimerization) as a key step. The approach
      opens a short and efficient access to a variety of novel compounds, some of which
      were found to exhibit significant and selective apoptosis-inducing activities
      against BJAB tumor cells.

PMID- 19093851
TI  - Palladium-catalyzed, one-pot, three-component synthesis of homoallylic amines
      from aldehydes, anisidine, and allyl trifluoroacetate.
AB  - An allylation reaction that generates homoallylic amines using allyl
      trifluoroacetate as a nucleophilic allylmetal precursor is reported. A palladium
      complex catalyzes two transformations in one pot: formation of allylsilane from
      allyl trifluoroacetate using hexamethyldisilane and subsequent imine allylation.
      A three-component reaction was developed where preformed imines were replaced
      with aldehydes and anisidine. Under these reaction conditions a variety of
      substrates, including electron-rich aromatic and aliphatic aldehydes, react
      smoothly to afford homoallylic amines.

PMID- 19093852
TI  - Comparative gas sensing in cobalt, nickel, copper, zinc, and metal-free
      phthalocyanine chemiresistors.
AB  - The sensitivities of metallophthalocyanine (MPcs: M = Co, Ni, Cu, Zn, and H(2))
      chemiresistors to vapor phase electron donors were examined using 50 nm MPc films
      deposited on interdigitated electrodes. Sensor responses were measured as changes
      in current at constant voltage. Analytes were chosen to span a broad range of
      Lewis base and hydrogen bond base strengths. The MPc sensor responses were
      correlated exponentially with binding enthalpy. These exponential fits were
      consistent with the van't Hoff equation and standard free energy relationships.
      Sensor recovery times were found to depend exponentially on binding enthalpy, in
      agreement with the Arrhenius equation. Relative sensitivities of all MPcs were
      compared via two-way ANOVA analysis. Array response patterns were differentiated
      via linear discriminant analysis, and analyte identification was achieved over a
      range of concentrations with 95.1% classification accuracy for the strong binding
      analytes. The ability to distinguish among different analytes, regardless of
      their concentration, through normalization of the responses to a reference sensor
      is particularly noteworthy.

PMID- 19093853
TI  - Effects of ZSM-5 zeolite confinement on reaction intermediates during dioxygen
      activation by enclosed dicopper cations.
AB  - We investigate how nanospaces surrounded by a 10-membered ring of ZSM-5 zeolite
      affect the reaction intermediates formed during dioxygen activation by enclosed
      dicopper cations. Two types of dioxygen intermediates are considered: one is an
      O(2)...Cu(2) complex, where dioxygen binds to the two Cu cations, and the other
      is a bis(mu-oxo)dicopper complex converted from an O(2)...Cu(2) complex by the
      cleavage of the O-O bond. We employ large-scale density functional theory (DFT)
      calculations with the B3LYP functional to examine the energetics of the two
      dioxygen intermediates inside a 10-membered ring of ZSM-5 with double Si --> Al
      substitutions at variable locations. The properties of the O(2)...Cu(2)
      complexes, such as the dioxygen bridging modes and dioxygen activation, are
      strongly affected by the locations of the two Al atoms within the 10-membered
      ring. In particular, the O(2)...Cu(2) complexes have either end-on or side-on
      bridging modes depending on the substituted Al positions. On the other hand, the
      steric hindrances of a ZSM-5 cavity play crucial roles in determining the
      properties of the bis(mu-oxo)dicopper complexes containing a diamond Cu(2)O(2)
      core. By restricting its Cu(2)O(2) core to a 10-membered ring of ZSM-5 in which
      the two Al atoms are second-nearest neighbors, each Cu cation is tetrahedral four
      coordinate. On the other hand, the Cu cations have almost square planar
      coordination inside a ZSM-5 where the Al atoms are fourth-nearest neighbors. The
      different Cu coordination environments are responsible for the different levels
      of stability; the planar diamond Cu(2)O(2) core is 30.7 kcal/mol more stable
      relative to the tetrahedral case. Since the ZSM-5 nanospaces directly influence
      the stability of the bis(mu-oxo)dicopper complexes by changing the Cu
      coordination environments, zeolite confinement effects on the bis(mu-oxo)dicopper
      complexes are more noticeable than those in the O(2)...Cu(2) cases. The DFT
      findings are important in terms of catalytic functions, because the spatial
      constraint from the ZSM-5 should significantly contribute to the stability of the
      reaction intermediates formed during the dioxygen activation.

PMID- 19093854
TI  - Manganese catalysts with molecular recognition functionality for selective alkene
      epoxidation.
AB  - Selective epoxidation of alkenes is possible with a new manganese porphyrin
      catalyst, C(PMR), that uses hydrogen bonding between the carboxylic acid on the
      substrate molecule and a Kemp's triacid unit. For two out of three olefin
      substrates employed, molecular recognition prevents the unselective oxidation of
      C-H bonds, and directs oxidation to the olefin moiety, giving only epoxide
      products. Weak diastereoselectivity is observed in the epoxide products,
      suggesting that molecular recognition affects the orientation of the catalyst
      bound substrate. The previously reported manganese terpyridine complex C(TMR) is
      shown to be a superior epoxidation catalyst to the porphyrin catalyst C(PMR).
      Good conversion of 2-cyclopentene acetic acid (substrate S2) with C(PMR) is
      consistent with molecular modeling, which indicates a particularly good
      substrate/catalyst match. Evidence suggests that hydrogen bonding between the
      substrate and the catalyst is critical in this system.

PMID- 19093855
TI  - In vivo SPECT and real-time gamma camera imaging of biodistribution and
      pharmacokinetics of siRNA delivery using an optimized radiolabeling and
      purification procedure.
AB  - Single photon emission computed tomography (SPECT) imaging provides a three
      dimensional method for exactly locating gamma emitters in a noninvasive procedure
      under in vivo conditions. For characterization of siRNA delivery systems,
      molecular imaging techniques are extremely helpful to follow biodistribution
      under in experimental animal studies. Quantification of biodistribution of siRNA
      and nonviral delivery systems using this technique requires efficient methods to
      stably label siRNA with a gamma emitter (e.g., 111In or 99mTc) and to purify
      labeled material from excesses of radiolabel or linkers. In the following study,
      we have optimized labeling and purification of siRNA, which was then applied as
      free siRNA or after complexation with polyethylenimine (PEI) 25 kDa for in vivo
      real-time gamma camera and SPECT imaging. Quantification of scintillation counts
      in regions of interest(ROIs) was compared to conventional scintillation counting
      of dissected organs, and the data acquired by imaging was shown to corroborate
      that of scintillation counting. This optimization and proof of principle study
      demonstrates that biodistribution and pharmacokinetics of siRNA and the
      corresponding polyplexes can be determined using SPECT, leading to comparable
      results as conventional methodology.

PMID- 19093856
TI  - Core expansion reactions of cyanamido/carbodiimido-bridged polynuclear iridium
      complexes.
AB  - Core expansion reactions of di- and tetrairidium complexes [Cp*Ir(mu(2)-NCN
      N,N)](2) (1; Cp* = eta(5)-C(5)Me(5)), [Cp*Ir(mu(3)-NCN-N,N,N)](4) (2), and
      phosphine derivatives of 1 have been investigated, and it has been revealed that
      cyanamido ligands in these complexes can change their coordination modes flexibly
      on reactions with a second transition metal complex. Treatment of diiridium
      complex 1 with [Cp*IrCl(2)](2) gives the tetrairidium complex [(Cp*Ir)(2)(mu(3)
      NCN-N,N,N')(2)(IrCp*Cl(2))(2)] (6) with mu(3)-kappaN,kappaN,kappaN' cyanoimido(2
      ) ligands. On the other hand, the reaction of 1 with [PdCl(eta(3)-C(3)H(5))](2)
      affords the NCN-bridged Ir(2)Pd(4) hexanuclear complex [(Cp*IrCl)(2)(mu(4)-NCN
      N,N,N',N')(2){Pd(2)(mu-Cl)(eta(3)-C(3)H(5))(2)}(2)] (7) and Ir(4)Pd(4)
      octanuclear complex [(Cp*Ir)(4)(mu(4)-NCN-N,N,N,N')(4){PdCl(eta(3)-C(3)H(5))}(4)]
      (8). The NCN-bridges in 7 provide the first example of the crystallographically
      determined mu(4)-kappaN,kappaN,kappaN',kappaN' carbodiimido(2-) ligand. Complex 8
      with mu(4)-kappaN,kappaN,kappaN,kappaN' cyanoimido(2-) ligands can also be
      synthesized selectively by the reaction of the parent cubane complex 2 with
      [PdCl(eta(3)-C(3)H(5))](2). Diphosphine derivative of 1, [{Cp*Ir(mu(2)
      NCN)}(2)(mu-dppm)] (4; dppm = Ph(2)PCH(2)PPh(2)), behaves differently on
      reactions with [PdCl(eta(3)-C(3)H(5))](2) and [MCl(cod)](2) (cod = cycloocta-1,5
      diene) to form the NCN-bridged Ir(2)M(2) (M = Pd, Rh, Ir) tetranuclear complexes
      [(Cp*Ir)(2)(mu(3)-NCN-N,N,N')(2){PdCl(eta(3)-C(3)H(5))}(2)(mu-dppm)] (9) and
      [(Cp*Ir)(2)(mu(3)-NCN-N,N,N')(2){MCl(cod)}(2)(mu-dppm)] (11a, M = Rh; 11b, M =
      Ir), respectively. The molecular structures for 6, 7, 8, 11a, and 11b have been
      determined by single-crystal X-ray analyses.

PMID- 19093857
TI  - Hydrophobic interactions determining functionalized lignocellulose solubility in
      dialkylimidazolium chlorides, as probed by 31P NMR.

PMID- 19093858
TI  - Structure and reactivity of alkynyl ruthenium alkylidenes.
AB  - The isolation and structural characterization of alkynyl Ru-alkylidene species
      has been elusive owing to their rapid metallotropic shift and fast turnover. The
      enyne ring-closing metathesis and relay metathesis provides the platform to form
      a variety of alkynyl Ru-alkylidene species possessing a sterically and
      electronically different substituent on the carbenic carbon, which allowed their
      regio-controlled trapping and structural characterization.

PMID- 19093859
TI  - A new catalytic Prins cyclization leading to oxa- and azacycles.
AB  - A new Prins cyclization process that builds up one carbon-carbon bond, one
      heteroatom-carbon bond, and one halogen-carbon bond, (in an oxa- and azacycle)
      relies on an iron catalyst system formed from Fe(acac)3 and trimethylsilyl
      halide. The method displays a broad substrate scope and is economical,
      environmentally friendly, and experimentally simple. This catalytic method
      permits the construction of chloro, bromo and iodo heterocycles, by the suitable
      combination of iron(III) source, the corresponding trimethylsilyl halide and the
      solvent, in high yields.

PMID- 19093860
TI  - Electron momentum spectroscopy study on valence electronic structures of
      ethylamine.
AB  - The valence-shell binding energy spectra and electron momentum profiles of
      gaseous ethylamine are measured by (e, 2e) electron momentum spectroscopy. When
      taking into account the Boltzmann-weighted abundance of 39% for trans and 61% for
      two equivalent gauche conformers coexisted in ethylamine, the thermally averaged
      electron momentum profiles for all valence orbitals calculated using B3LYP method
      with 6-311++G** and aug-cc-pVTZ basis sets reproduce the experimental ones well,
      which supports that the trans conformer is more stable. In addition, the
      controversial ordering of 2a'' and 7a' orbitals for the trans conformer is
      reassigned and an ionization band at about 13.7 eV, which was uncertain in
      previous literatures, is confirmed by comparing the experimental momentum
      profiles with the theoretical ones for the respective molecular orbitals.
      Furthermore, the ionization potentials and pole strengths for the inner valence
      orbitals are reported for the first time.

PMID- 19093861
TI  - By how much is protonated benzene stabilized by coordination of iron tricarbonyl?
AB  - Rate and equilibrium measurements for the hydrolysis of the Fe(CO)3-coordinated
      cyclohexadienyl cation lead to pKR = 4.7 compared with pKR = -2.1 for the
      uncoordinated ion. The hydrolysis yields exo-coordinated cyclohexadienol 10(7)
      fold more rapidly than its endo-isomer, despite the isomers being of similar
      stability. DFT calculations of the energy of isodesmic transfer of Fe(CO)3 from
      cyclohexadiene to benzene lead to an estimate of pKa 8 for loss of a proton from
      the coordinated cyclohexadienyl cation to form Fe(CO)3-coordinated benzene. This
      implies that the coordinated cation is 33 log units (46 kcal) less acidic than
      the uncoordinated ion.

PMID- 19093862
TI  - Photoreactivity of As-fabricated Au clusters at the single-cluster level.
AB  - In this study, we have photochemically fabricated a gold cluster (Au(n)),
      composed of several tens of atoms, in a polymer matrix and concurrently
      investigated the photoreactivity of newly formed clusters at the single-cluster
      level. Our attempt enabled the in situ observation of individual ligand-free
      Au(n) clusters with a resolution of the number of atoms. In addition, the
      procedure revealed the photoinduced reaction of excited Au(n) clusters with O(2)
      for the first time.

PMID- 19093863
TI  - Hydroxynaphthyridine-derived group III metal chelates: wide band gap and deep
      blue analogues of green Alq3 (tris(8-hydroxyquinolate)aluminum) and their
      versatile applications for organic light-emitting diodes.
AB  - A series of group III metal chelates have been synthesized and characterized for
      the versatile application of organic light-emitting diodes (OLEDs). These metal
      chelates are based on 4-hydroxy-1,5-naphthyridine derivates as chelating ligands,
      and they are the blue version analogues of well-known green fluorophore Alq(3)
      (tris(8-hydroxyquinolinato)aluminum). These chelating ligands and their metal
      chelates were easily prepared with an improved synthetic method, and they were
      facially purified by a sublimation process, which enables the materials to be
      readily available in bulk quantity and facilitates their usage in OLEDs. Unlike
      most currently known blue analogues of Alq(3) or other deep blue materials, metal
      chelates of 4-hydroxy-1,5-naphthyridine exhibit very deep blue fluorescence, wide
      band gap energy, high charge carrier mobility, and superior thermal stability.
      Using a vacuum-thermal-deposition process in the fabrication of OLEDs, we have
      successfully demonstrated that the application of these unusual
      hydroxynaphthyridine metal chelates can be very versatile and effective. First,
      we have solved or alleviated the problem of exciplex formation that took place
      between the hole-transporting layer and hydroxynaphthyridine metal chelates, of
      which OLED application has been prohibited to date. Second, these deep blue
      materials can play various roles in OLED application. They can be a highly
      efficient nondopant deep blue emitter: maximum external quantum efficiency
      eta(ext) of 4.2%; Commision Internationale de L'Eclairage x, y coordinates,
      CIE(x,y) = 0.15, 0.07. Compared with Alq(3), Bebq(2) (beryllium bis(benzoquinolin
      10-olate)), or TPBI (2,2',2''-(1,3,5-phenylene)tris(1-phenyl-1H-benzimidazole),
      they are a good electron-transporting material: low HOMO energy level of 6.4-6.5
      eV and not so high LUMO energy level of 3.0-3.3 eV. They can be ambipolar and
      possess a high electron mobility of 10(-4) cm(2)/V s at an electric field of 6.4
      x 10(5) V/cm. They are a qualified wide band gap host material for efficient blue
      perylene (CIE(x,y) = 0.14, 0.17 and maximum eta(ext) 3.8%) or deep blue 9,10
      diphenylanthracene (CIE(x,y) = 0.15, 0.06 and maximum eta(ext) 2.8%). For solid
      state lighting application, they are desirable as a host material for yellow
      dopant (rubrene) in achieving high efficiency (eta(ext) 4.3% and eta(P) 8.7 lm/W
      at an electroluminance of 100 cd/m(2) or eta(ext) 3.9% and eta(P) 5.1 lm/W at an
      electroluminance of 1000 cd/m(2)) white electroluminescence (CIE(x,y) = 0.30,
      0.35).

PMID- 19093865
TI  - White-light emitting hydrogen-bonded supramolecular copolymers based on pi
      conjugated oligomers.
AB  - Three different pi-conjugated oligomers (a blue-emitting oligofluorene, a green
      emitting oligo(phenylene vinylene), and a red-emitting perylene bisimide) have
      been functionalized with self-complementary quadruple hydrogen bonding
      ureidopyrimidinone (UPy) units at both ends. The molecules self-assemble in
      solution and in the bulk, forming supramolecular polymers. When mixed together in
      solution, random noncovalent copolymers are formed that contain all three types
      of chromophores, resulting in energy transfer upon excitation of the
      oligofluorene energy donor. At a certain mixing ratio, a white emissive
      supramolecular polymer can be created in solution. In contrast to their
      unfunctionalized counterparts, bis-UPy-chromophores can easily be deposited as
      smooth thin films on surfaces by spin coating. No phase separation is observed in
      these films, and energy transfer is much more efficient than in solution, giving
      rise to white fluorescence at much lower ratios of energy acceptor to donor.
      Light emitting diodes based on these supramolecular polymers have been prepared
      from all three types of pure materials, yielding blue, green, and red devices,
      respectively. At appropriate mixing ratios of these three compounds, white
      electroluminescence is observed. This approach yields a toolbox of molecules that
      can be easily used to construct pi-conjugated supramolecular polymers with a
      variety of compositions, high solution viscosities, and tuneable emission colors.

PMID- 19093864
TI  - On the mechanism of nitrosoarene-alkyne cycloaddition.
AB  - The thermal reaction between nitrosoarenes and alkynes produces N-hydroxyindoles
      as the major products. The mechanism of these novel reactions has been probed
      using a combination of experimental and computational methods. The reaction of
      nitrosobenzene (NB) with an excess of phenyl acetylene (PA) is determined to be
      first order in each reactant in benzene at 75 degrees C. The reaction rates have
      been determined for reactions between phenyl acetylene with a set of p
      substituted nitrosoarenes, 4-X-C(6)H(4)NO, and of 4-O(2)N-C(6)H(4)NO with a set
      of p-substituted arylalkynes, 4-Y-C(6)H(4)C[triple bond]CH. The former reactions
      are accelerated by electron-withdrawing X groups (rho = +0.4), while the latter
      are faster with electron-donating Y groups (rho = -0.9). The kinetic isotope
      effect for the reaction of C(6)H(5)NO/C(6)D(5)NO with PhC[triple bond]CH is found
      to be 1.1 (+/-0.1) while that between PhC[triple bond]CH/PhC[triple bond]CD with
      PhNO is also 1.1 (+/-0.1). The reaction between nitrosobenzene and the radical
      clock probe cyclopropylacetylene affords 3-cyclopropyl indole in low yield. In
      addition to 3-carbomethoxy-N-hydroxyindole, the reaction between PA and o
      carbomethoxy-nitrosobenzene also affords a tricyclic indole derivative, 3, likely
      derived from trapping of an intermediate indoline nitrone with PA and subsequent
      rearrangement. Computational studies of the reaction mechanism were carried out
      with density functional theory at the (U)B3LYP/6-31+G(d) level. The lowest energy
      pathway of the reaction of PhNO with alkynes was found to be stepwise; the N-C
      bond between nitrosoarene and acetylene is formed first, the resulting vinyl
      diradical undergoes cis-trans isomerization, and then the C-C bond forms.
      Conjugating substituents Z on the alkyne, Z-C[triple bond]CH, lower the
      calculated (and observed) activation barrier, Z = -H (19 kcal/mol), -Ph (15.8
      kcal/mol), and -C(O)H (13 kcal/mol). The regioselectivity of the reaction, with
      formation of the 3-substituted indole, was reproduced by the calculations of PhNO
      + PhC[triple bond]CH; the rate-limiting step for formation of the 2-substituted
      indole is higher in energy by 11.6 kcal/mol. The effects of -NO(2), -CN, -Cl, 
      Br, -Me, and -OMe substituents were computed for the reactions of p-X-C(6)H(4)NO
      with PhC[triple bond]CH and of PhNO and/or p-NO(2)-C(6)H(4)NO with p-Y
      C(6)H(4)C[triple bond]CH. The activation energies for the set of p-X-C(6)H(4)NO
      vary by 4.3 kcal/mol and follow the trend found experimentally, with electron
      withdrawing X groups accelerating the reactions. The range of barriers for the p
      Y-C(6)H(4)C[triple bond]CH reactions is smaller, about 1.5 and 1.8 kcal/mol in
      the cases of PhNO and p-NO(2)-PhNO, respectively. In agreement with the
      experiments, electron-donating Y groups on the alkyne accelerate the reactions
      with p-NO(2)-C(6)H(4)NO, while both ED and EW groups are predicted to facilitate
      the reaction. The calculated kinetic isotope effect for the reaction of
      C(6)H(5)NO/C(6)D(5)NO with PhC[triple bond]CH is negligible (as found
      experimentally) while that for PhC[triple bond]CH/PhC[triple bond]CD with PhNO
      (0.7) differs somewhat from the experiment (1.1). Taken together the experimental
      and computational results point to the operation of a stepwise diradical
      cycloaddition, with rate-limiting N-C bond formation and rapid C-C connection to
      form a bicyclic cyclohexadienyl-N-oxyl diradical, followed by fast
      tautomerization to the N-hydroxyindole product.

PMID- 19093866
TI  - Effect of high oxygen atmosphere storage on quality, antioxidant enzymes, and
      DPPH-radical scavenging activity of Chinese bayberry fruit.
AB  - The influence of high O(2) atmosphere on postharvest decay, quality, total
      phenolic, total anthocyanin contents, antioxidant enzymes activity, and
      antioxidant activity of Chinese bayberry fruit was investigated. Freshly
      harvested Chinese bayberry fruits were placed in jars and ventilated continuously
      with air or with 80 and 100% O(2) for up to 12 days. Samples were randomly
      selected initially and at 3-days interval during storage. The fruit exposed to
      high O(2) was resistant to decay, had high levels of total soluble solids,
      titratable acidity and ascorbic acid contents, and also reduced the increment of
      pH value. High O(2) treatment was less stressful as reflected by having the
      significantly lower malonaldehyde contents and higher catalase, ascorbic acid
      peroxidase, and peroxidase activities during storage. Both 80% and 100% O(2)
      treaments had also retained the bioactive contents and 1,1-diphenyl-2
      picrylhydrazyl radical scavenging activity during storage. These results indicate
      that elevated O(2) levels may improve the ability of the antioxidative defense
      mechanism in Chinese bayberry and result in a better control of fruit decay.

PMID- 19093867
TI  - Changes in the fatty acid composition of M. longissimus dorsi of lamb during
      storage in a high-oxygen modified atmosphere at different levels of dietary
      vitamin E supplementation.
AB  - The effect of vitamin E supplementation on fatty acid composition during storage
      of lamb meat packed in a high-oxygen modified atmosphere was studied. Lambs were
      fed with diets supplemented with four levels of vitamin E (0, 250, 500, and 1000
      mg acetate-alpha-tocopherol/kg feed). Slices of M. longissimus dorsi were packed
      in a high-oxygen modified atmosphere (70% O2:30% CO2) and stored at 2 +/- 1
      degrees C in the dark for 14, 21, and 28 days. The nonsupplemented group (E0)
      showed an increase in saturated fatty acids (SFA) and monounsaturated fatty acids
      and a reduction in polyunsaturated fatty acids (PUFA) in total fatty acids. The
      proportion of SFA and PUFA was unchanged in the supplemented groups (E250, E500,
      and E1000). The supplementation with 250 mg acetate-alpha-tocopherol/kg feed
      prevented the oxidation of PUFA in the total lipids and in the polar lipids
      fraction, while 500 mg acetate-alpha-tocopherol/kg feed was necessary to prevent
      the oxidation of PUFA in free fatty acids. Supplementing vitamin E not only
      inhibited lipid oxidation but also maintained nutritional value [essential fatty
      acids, linoleic acid (C18:2n-6) and linolenic acid (C18:3n-3), and beneficial
      fatty acids, eicosapentaenoic acid (C20:5n-3) and docosahexaenoic acid (C22:6n
      3)] throughout the storage period.

PMID- 19093868
TI  - Curcumin exerts antidifferentiation effect through AMPKalpha-PPAR-gamma in 3T3-L1
      adipocytes and antiproliferatory effect through AMPKalpha-COX-2 in cancer cells.
AB  - Curcumin has been reported to have the potential to prevent obesity as well as
      cancers. The downstream targets regulated by AMP-activated protein kinase (AMPK)
      for inhibiting adipocyte differentiation or cancer cell proliferation of curcumin
      were investigated. The activation of AMPK by curcumin was crucial for the
      inhibition of differentiation or growth in both adipocytes and cancer cells.
      Stimulation of AMPK by curcumin resulted in the down-regulation of PPAR
      (peroxisome proliferator-activated receptor)-gamma in 3T3-L1 adipocytes and the
      decrease in COX-2 in MCF-7 cells. Application of a synthetic AMPK activator also
      supported the evidence that AMPK acts as an upstream signal of PPAR-gamma in 3T3
      L1 adipocytes. In cancer cells, AMPK was found to act as a regulator of ERK1/2,
      p38, and COX-2. Regulation of AMPK and its downstream targets such as PPAR-gamma,
      Mapkinases, and COX-2 by curcumin appears to be important in controlling
      adipocytes and cancerous cells.

PMID- 19093869
TI  - Structural investigations and morphology of tomato fruit starch.
AB  - The physicochemical properties of starch from tomato (Solanum lycopersicum L.)
      pericarp and columella of cv. Moneymaker fruit at 28 days post anthesis (DPA)
      were investigated, providing the first description of the composition and
      structure of tomato fruit starch. Starch granules from pericarp were mainly
      polygonal, 13.5-14.3 microm, and increased in size through development, being
      largest in ripening fruit. Amylopectin content was 81-83% and was of molecular
      weight 1.01 x 10(8) g/mol; the phosphorus content was 139 ppm, and starch showed
      a C-type pattern with crystallinity of 30%. Starch characteristics were similar
      in columella except granule size (16.8-17.8 microm) and crystallinity (40%),
      although 6-fold more starch accumulated in the pericarp. Solara, a high-sugar
      tomato cultivar, was also studied to determine if this affects starch granule
      architecture. There were few differences from Moneymaker, except that Solara
      columella starch crystallinity was lower (26%), and more starch granule-intrinsic
      proteins could be extracted by sodium dodecyl sulfate-polyacrylamide gel
      electrophoresis.

PMID- 19093870
TI  - Lectin conjugated gastroretentive multiparticulate delivery system of
      clarithromycin for the effective treatment of Helicobacter pylori.
AB  - The aim of the research work was to develop and characterize a concanavalin-A
      (Con-A) conjugated gastroretentive multiparticulate delivery system of
      clarithromycin (CM) for the effective treatment of colonization of Helicobacter
      pylori (H. pylori). Ethylcellulose (EC) microspheres containing CM were prepared
      using emulsification/ evaporation method. Formulations were characterized for
      micromeritic properties, % drug entrapment, % yield, surface morphology, buoyancy
      behavior and in vitro drug release in simulated gastric fluid. EC microspheres of
      CM were conjugated with Con-A. IR spectroscopy and differential scanning
      calorimetry were used to confirm conjugation of Con-A to EC microspheres while
      Con-A conjugated microspheres were further characterized using the parameters of
      zeta potential, mucoadhesiveness to gastric mucosa and Con-A conjugation
      efficiency with microspheres. The gamma scintigraphy of the formulations was
      carried out in albino rabbits (New Zealand) to monitor the transit of Con-A
      conjugated EC microspheres and marketed formulation in gastrointestinal (GI)
      tract. The microparticles were found to be regular and spherical in shape. The
      particle size of microspheres was found to vary from 112.45 +/- 3.39 to 124.23 +/
      2.31 microm with polymer concentration from 1% w/v to 3% w/v. IR and DSC studies
      confirmed the attachment of Con-A with EC microspheres. All the microsphere
      formulations showed good % drug entrapment (70 +/- 3%). Zeta potential of EC
      microspheres and Con-A conjugated EC microspheres was found to be -8.77 +/- 0.5
      mV and 7.56 +/- 0.7 mV, respectively. Maximum mucoadhesion (85 +/- 2.6%) was
      shown by Con-A conjugated EC microspheres as compared with nonconjugated EC
      microspheres (12.0 +/- 3.2%). Performance of developed formulation in GI tract
      was visualized successfully by gamma scintigraphy in rabbits. Prolonged gastric
      residence time (GRT) of over 6 h was achieved in all rabbits for Con-A conjugated
      microspheres of CM. It is concluded that designed targeted delivery system could
      possibly treat the colonization of H. pylori.

PMID- 19093872
TI  - Bridged bis(amidinate) ytterbium alkoxide and phenoxide: syntheses, structures,
      and their high activity for controlled polymerization of L-lactide and epsilon
      caprolactone.
AB  - Bridged bis(amidinate) ytterbium alkoxide and phenoxide with diverse molecular
      structures were synthesized in high yields and confirmed by X-ray crystal
      structural analysis. The reaction of LYbCl(THF)(2) (L =
      Me(3)SiNC(Ph)N(CH(2))(3)NC(Ph)NSiMe(3)) with 1 equiv of NaOAr (ArO = 2,6
      diisopropylphenoxo) afforded the mononuclear complex LYb(OAr)DME 1 with a seven
      coordinated ytterbium atom surrounded by one chelating bis(amidinate) ligand, one
      phenoxo group, and one DME (dimethoxyethane) molecule. The same reaction with 1
      equiv of NaO(i)Pr yielded the binuclear complex Yb(mu(2)-L)(2)(mu(2)
      O(i)Pr)(2)Yb, 2, with two equivalent six-coordinate metal centers connected by
      two linked bis(amidinate)s and two O(i)Pr bridges formed via a ligand
      redistribution reaction that occurred during the metathesis reaction. Both 1 and
      2 initiated the ring-opening polymerization of L-lactide, as well as epsilon
      caprolactone (epsilon-CL), in a controlled manner with high reactivity, as
      indicated by a linear relationship between M(n) and conversion and by narrow
      molecular weight distributions (PDI = 1.15-1.25) up to 100% conversion. The
      differences in catalytic performance between complexes 1 and 2 are discussed.

PMID- 19093871
TI  - Antibody-mediated targeting of siRNA via the human insulin receptor using avidin
      biotin technology.
AB  - Delivery of short interfering RNA (siRNA) to cells in culture, and in vivo, is
      possible with combined use of a receptor-specific monoclonal antibody (mAb) and
      avidin-biotin technology. In the present studies, the luciferase gene is
      transiently expressed in human 293 epithelial cells. The siRNA delivery system is
      composed of the siRNA, monobiotinylated on the 3'-terminus of the sense strand,
      and a conjugate of streptavidin (SA) and a mAb to the human insulin receptor
      (HIR). Exposure of cells to 3'-biotinyl-siRNA bound to the HIRMAb/SA conjugate,
      but not to unconjugated SA, avidin, or the HIRMAb, causes a >90% reduction in
      luciferase gene expression. The receptor-targeted siRNA effect is maximal at 48 h
      after delivery of the siRNA to the cells, and the effect is lost by 7 days after
      a single application of the targeted siRNA in culture. The KI of the receptor
      targeted siRNA inhibition of gene expression is 30.5 +/- 11.7 nM, and significant
      inhibition is observed with siRNA concentrations as low as 3 nM. In conclusion,
      the combination of a receptor-specific targeting ligand, such as the HIRMAb, and
      avidin-biotin technology allows for high affinity capture of the monobiotinylated
      siRNA by the targeting mAb. The siRNA is effectively delivered to the cytosol of
      cells, and knockdown of gene expression with the HIRMAb/SA delivery system is
      comparable to RNA interference effects obtained with cationic polyplexes. Whereas
      the use of cationic polyplexes in vivo is problematic, the bond between the
      targeting mAb and the siRNA is stable with avidin-biotin technology, and RNAi
      effects at distant sites such as brain are observed in vivo following an
      intravenous administration of the targeted siRNA.

PMID- 19093873
TI  - 2D-DIGE as a strategy to identify serum markers for the progression of prostate
      cancer.
AB  - Prostate cancer is the most common solid organ malignancy affecting men in the
      United States and Western Europe. Currently, the main diagnostic tools used to
      look for evidence of prostate cancer include physical examination using digital
      rectal exam (DRE), serum concentrations of prostate specific antigen (PSA) and
      biopsy. However, due to the low specificity of PSA in differentiating prostate
      cancer from other benign conditions, many patients undergo overtreatment for
      their disease. There is an urgent need for additional markers to improve the
      diagnostic accuracy for early stages of prostate cancer. Proteomic analysis of
      serum has the potential to identify such markers. An initial discovery study has
      been completed using 12 serum samples from patients with different grades of
      prostate cancer (Gleason score 5 and 7) undergoing radical prostatectomy. Serum
      samples were subjected to immunoaffinity depletion and protein expression
      analysis using 2D-DIGE. Image analysis isolated 63 spots that displayed
      differential expression between the Gleason score 5 and 7 cohorts (p < 0.05), 13
      of which were identified as statistically significant using two independent image
      analysis packages. Identification of differentially expressed spots was carried
      out using LC-MS/MS. Because of their functional relevance and potential
      significance with regards to prostate cancer progression, two of these proteins,
      pigment epithelium-derived factor (PEDF) and zinc-alpha2-glycoprotein (ZAG), have
      undergone extensive validation in serum and tissue samples from the original
      cohort and also from a larger independent cohort of patients. These results have
      indicated that PEDF is a more accurate predictor of early stage prostate cancer.
      We are confident that proteomics-based approaches have the potential to provide
      more insight into the underlying molecular mechanisms of the disease and also
      hold great promise for biomarker discovery in prostate cancer.

PMID- 19093875
TI  - N-glycosylation pattern of E2 glycoprotein from classical swine fever virus.
AB  - The extracellular domain of E2 glycoprotein outer surface of the classical swine
      fever virus was expressed in epithelial kidney pig cells. The N-glycosylation
      determined by combination of Normal Phase-HPLC, Weak Anion Exchange-HPLC,
      exoglycosidase digestions and Mass Spectrometry revealed a complex mixture of
      neutral and monosialylated multiantennary N-glycans with variable number of
      alpha1-3-Gal-Gal antennae terminals. The most abundant neutral N-glycan has a
      composition of Hex(7)HexNAc(4)dHex(1), Negative ion ESI-MS/MS confirmed the
      presence of the alpha1-3-Gal-Gal motif on each arm of the fucosylated biantennary
      N-glycan. The most abundant monosialylated glycan was
      Hex(6)HexNAc(4)dHex(1)Neu(5)Ac(1), with the sialic acid linked to the terminal
      beta1-4-Gal-GlcNAc. Sialic acid on the antenna capping position was predominantly
      of the N-acetyl form.

PMID- 19093874
TI  - A perspective on the Maillard reaction and the analysis of protein glycation by
      mass spectrometry: probing the pathogenesis of chronic disease.
AB  - The Maillard reaction, starting from the glycation of protein and progressing to
      the formation of advanced glycation end-products (AGEs), is implicated in the
      development of complications of diabetes mellitus, as well as in the pathogenesis
      of cardiovascular, renal, and neurodegenerative diseases. In this perspective
      review, we provide an overview on the relevance of the Maillard reaction in the
      pathogenesis of chronic disease and discuss traditional approaches and recent
      developments in the analysis of glycated proteins by mass spectrometry. We
      propose that proteomics approaches, particularly bottom-up proteomics, will play
      a significant role in analyses of clinical samples leading to the identification
      of new markers of disease development and progression.

PMID- 19093876
TI  - Elucidation of O-glycosylation structures of the beta-amyloid precursor protein
      by liquid chromatography-mass spectrometry using electron transfer dissociation
      and collision induced dissociation.
AB  - Accumulation and deposition of beta-amyloid peptide, a major constituent in
      neuritic plaques are hallmarks of Alzheimer's disease (AD) and AD-related
      neurodegenerative diseases. beta-Amyloid (Abeta) is derived from the proteolytic
      cleavage of amyloid precursor protein (APP), a transmembrane protein present in
      three major isoforms in brain comprising 695, 751 and 770 amino acids,
      respectively. Among other post-translational modifications, APP is modified
      during maturation by N- and O-glycosylation, which are thought to be responsible
      for its expression and secretion. Unlike N-glycosylation, no sites of O
      glycosylation of APP have previously been reported. We report here the
      identification of three specific O-glycosylation sites of the secreted APP695
      (sAPP695) produced in CHO cells, using a combination of high-performance liquid
      chromatography and electrospray-tandem mass spectrometry. With the use of
      electron transfer dissociation and collision induced dissociation (ETD and CID),
      we identified type, composition and structures of the Core 1 type O-linked
      glycans attached at the residues Thr 291, Thr 292 and Thr 576 of the full-length
      APP695. The glycosylations comprise multiple short glycans, containing N-acetyl
      galactosamine (GalNAc), Gal-GalNAc and sialic acid terminated structures. The
      presence of the glycopeptides in the tryptic mixture was identified using the CID
      generated sugar oxonium ions. ETD proved to be valuable for the unambiguous
      identification of the modified sites as ETD fragmentation occurred along the
      peptide backbone with little or no cleavage of the glycans. Thus, the combination
      of the CID and ETD techniques in LC-MS is shown here, as a powerful tool for de
      novo identification of O-glycosylations at unknown modification sites in
      proteins.

PMID- 19093877
TI  - Photodynamic molecular beacon triggered by fibroblast activation protein on
      cancer-associated fibroblasts for diagnosis and treatment of epithelial cancers.
AB  - Fibroblast activation protein (FAP) is a cell-surface serine protease highly
      expressed on cancer-associated fibroblasts of human epithelial carcinomas but not
      on normal fibroblasts, normal tissues, and cancer cells. We report herein a novel
      FAP-triggered photodynamic molecular beacon (FAP-PPB) comprising a fluorescent
      photosensitizer and a black hole quencher 3 linked by a peptide sequence
      (TSGPNQEQK) specific to FAP. FAP-PPB was effectively cleaved by both human FAP
      and murine FAP. By use of the HEK293 transfected cells (HEK-mFAP, FAP(+); HEK
      vector, FAP(-)), systematic in vitro and in vivo experiments validated the FAP
      specific activation of FAP-PPB in cancer cells and mouse xenografts,
      respectively. FAP-PPB was cleaved by FAP, allowing fluorescence restoration in
      FAP-expressing cells while leaving non-expressing FAP cells undetectable.
      Moreover, FAP-PPB showed FAP-specific photocytotoxicity toward HEK-mFAP cells
      whereas it was non-cytotoxic toward HEK-Vector cells. This study suggests that
      the FAP-PPB is a potentially useful tool for epithelial cancer detection and
      treatment.

PMID- 19093878
TI  - Study of the effect of sample preparation and cooking on the selenium speciation
      of selenized potatoes by HPLC with ICP-MS and electrospray ionization MS/MS.
AB  - The efficiency of enzymatic hydrolysis and leaching with water using accelerated
      solvent extraction (ASE) or boiling was investigated for quantitative Se
      speciation in selenized potatoes using reversed phase HPLC coupled to ICP-MS.
      Preliminary identification of selenomethionine (SeMet), Se-methylselenocysteine
      (SeMeCys), and selenate in extracts of potato skin and flesh was achieved using
      complementary reversed phase and anion-exchange HPLC-ICP-MS and retention time
      matching with standards. The quantitative speciation data revealed a higher
      percentage of selenomethionine (73% of the total Se) found in the flesh in
      comparison with skin (containing 21% of the total Se as SeMet). ASE and boiling
      in water were found to be similar in terms of Se extraction efficiency and
      profiles. However, ASE was found to be more efficient than boiling with respect
      to sample cleanup and reduced sample handling. The presence of SeMet at parts per
      billion levels in selenized potatoes was confirmed by reversed phase HPLC with
      online ESI MS/MS.

PMID- 19093879
TI  - Glycoprotein synthesis: an update.

PMID- 19093880
TI  - Free volume dependence of the internal rotation of a molecular rotor probe in
      room temperature ionic liquids.
AB  - The fluorescence efficiency of a well-known microviscosity probe, 9
      (dicyanovinyl)julolidine (DCVJ), which is highly sensitive to the viscosity of
      the medium, has been studied in seven imidazolium ionic liquids (ILs) of varying
      viscosities over a temperature range of 10-60 degrees C. The microviscosities
      around the probe in different ILs have been estimated from the linear dependence
      of the logarithm of fluorescence quantum yield (log phi(f)) on the logarithm of
      the bulk viscosity (log eta) in various conventional solvents of different
      viscosities at room temperature. These microviscosities, which represent the
      local environments around the probe, are found to be significantly different from
      the directly measured bulk viscosities of these ILs. The log phi(f) vs log
      (eta/T) plots, which are also expected to be linear, interestingly show a
      bilinear behavior in more viscous ILs with a break around 28-30 degrees C. The
      observation of a similar break in the Arrhenius plots of the rate constant of the
      internal rotation in DCVJ and absence of any such break in the temperature
      dependence of the mobility of the ILs allow us to determine the important role of
      the free volume around the probe in dictating the nonradiative deactivation rate
      or the fluorescence efficiency of DCVJ. The break in the plots, which implies a
      change in the available free volume around the probe at approximately 28-30
      degrees C, presumably arises from the repositioning of the probe from one
      environment to a different one of these microheterogeneous ILs with change of
      temperature.

PMID- 19093881
TI  - Molecular dynamic simulation of the Kv1.2 voltage-gated potassium channel in open
      and closed state conformations.
AB  - We performed 45 ns atomistic force field based molecular dynamics (MD)
      simulations to explore the structure and dynamics of the Kvl.2 voltage-dependent
      potassium ion channel in both open and closed state conformations. The Kv1.2
      crystal structure (PDB 2A79) based open state model and homologically derived
      closed state model are embedded in a hydrated lipid membrane. We present a
      detailed analysis of the protein stability, the environment of the gating-charge
      carrying residues, the salt bridge within the voltage sensor, S4 segment helix
      movement, helix interaction between S4-S5 linker and S6, interaction between
      subunits, and interaction between protein and lipid membrane. The four subunits
      of the channel lost the symmetry from the starting structure during the
      simulation, especially the voltage sensors. According to our comparative analysis
      of the open and closed state conformations, S4 in our simulation behaves more
      near the screw helix model except for the tilt action. The S4 segment azimuthal
      rotation angle difference between two conformations shifts about 60 degrees after
      being embedded in a membrane environment. The S4-S5 linker helix remains stable.
      The contact area between the S4 and S5 from the adjacent subunit increases after
      transition to the closed state from the open state. The current investigation
      provided valuable information to our understanding of the structure and dynamics
      of membrane-associated helices and the gating mechanism of the voltage-dependent
      potassium ion channel of the Kv channel.

PMID- 19093882
TI  - Codrugs linking L-dopa and sulfur-containing antioxidants: new pharmacological
      tools against Parkinson's disease.
AB  - A series of multifunctional codrugs (1-6) were synthesized to overcome the pro
      oxidant effect associated with L-dopa (LD) therapy. Target compounds release LD
      and dopamine (DA) in human plasma after enzymatic hydrolysis, displaying an
      antioxidant effect superior to that of N-acetylcysteine (NAC). After
      intracerebroventricular injection of codrug 4, the levels of DA in the striatum
      were higher than those in LD-treated groups, indicating that this compound has a
      longer half-life in brain than LD.

PMID- 19093883
TI  - Inhibition of MDR1 activity in vitro by a novel class of diltiazem analogues:
      toward new candidates.
AB  - The reversal of multidrug resistance by 22 molecules [8-aryl-8-hydroxy-5-R'-8H
      [1,4]thiazino[3,4-c][1,2,4]oxadiazol-3-ones (1a-i) and 8-aryl-8-alkoxy-5-methyl
      8H-[1,4]thiazino[3,4-c][1,2,4]oxadiazol-3-ones (2a-m)] related to myocardial
      calcium-channel-modulator diltiazem was studied in multidrug resistant A2780/DX3
      and their sensitive counterpart A2780 cells. MTT, cytofluorimetry assays, and
      fluorescence microscopy analyses were used to define activity and accumulation of
      doxorubicin with or without the diltiazem-like modulators. Of the 22 molecules,
      1a, 2f, 2g, and 2m were able to overcome the established criteria for the
      selection in A2780/DX3 cells (IC(50) reduction > or = 25%), but only 2f, 2g, and
      2m caused a significant increase of intracellular accumulation of doxorubicin. In
      conclusion, experiments lead to the identification of three diltiazem-like
      molecules able to increase the intracellular accumulation of doxorubicin by
      inhibiting the MDR1 function, thus potentiating its antiproliferative activity in
      multidrug resistant A2780/DX3 cells.

PMID- 19093885
TI  - Detection and assignment of common scaffolds in project databases of lead
      molecules.
AB  - A method is presented for the detection and analysis of multiple common scaffolds
      for small collections of pharmaceutically relevant molecules that share a set of
      common structural motifs. The input consists of the molecules themselves,
      possibly some of the scaffolds, and possibly information about the relation
      between the substitution points of these scaffolds. Three new algorithms are
      presented: multiple scaffold detection, common scaffold alignment, and scaffold
      substructure assignment. Each of these steps is relevant for cases when either
      none, some, or all information about the common scaffolds and their substitution
      patterns is available. Each of these problems must be solved in an optimal way in
      order to produce useful structure-activity correlations. The output consists of a
      collection of scaffolds, a common numbering system, and a unique mapping of each
      molecule to a single scaffold substructure. This information can then be used to
      produce data for structure-activity analysis of medicinal chemistry project
      databases.

PMID- 19093884
TI  - Non-peptide macrocyclic histone deacetylase inhibitors.
AB  - Inhibition of histone deacetylase inhibitors (HDACi) hold great promise in cancer
      therapy because of their demonstrated ability to arrest proliferation of nearly
      all transformed cell types. Of the several structurally distinct small molecule
      HDACi reported, macrocyclic depsipeptides have the most complex recognition cap
      group moieties and present an excellent opportunity for the modulation of the
      biological activities of HDACi. Unfortunately, the structure-activity
      relationship (SAR) studies for this class of compounds have been impaired largely
      because most macrocyclic HDACi known to date comprise complex peptide
      macrocycles. In addition to retaining the pharmacologically disadvantaged
      peptidyl backbone, they offer only limited opportunity for side chain
      modifications. Here, we report the discovery of a new class of macrocyclic HDACi
      based on the macrolide antibiotics skeletons. SAR studies revealed that these
      compounds displayed both linker-length and macrolide-type dependent HDAC
      inhibition activities with IC(50) in the low nanomolar range. In addition, these
      non-peptide macrocyclic HDACi are more selective against HDACs 1 and 2 relative
      to HDAC 8, another class I HDAC isoform, and hence have subclass HDAC isoform
      selectivity.

PMID- 19093886
TI  - AcOLeDMAP and BnOLeDMAP: conformationally restricted nucleophilic catalysts for
      enantioselective rearrangement of indolyl acetates and carbonates.
AB  - The rate of indolyl O- to C-acetyl or carboxyl rearrangement is accelerated by
      the electron-withdrawing N-diphenylacetyl group (DPA) using the conformationally
      restricted chiral catalysts AcOLeDMAP (12b) and BnOLeDMAP (13b). Highly
      enantioselective conversion to quaternary C-acetylated and C-carboxylated
      oxindoles is observed, even for substrates containing branched substituents. The
      rearrangement of the carboxylate substrates 19 occurs with complementary
      enantiofacial selectivity using catalyst 13b compared to the acetyl migrations of
      16 catalyzed by 12b. Access to N-unsubstituted oxindoles is demonstrated by DPA
      cleavage with Et(2)NH.

PMID- 19093890
TI  - How we got here, where we are going and being a cog in something turning.

PMID- 19093893
TI  - Human neural cell interactions with orientated electrospun nanofibers in vitro.
AB  - AIM: Electrospun nanofibers represent potent guidance substrates for nervous
      tissue repair. Development of nanofiber-based scaffolds for CNS repair requires,
      as a first step, an understanding of appropriate neural cell type-substrate
      interactions. MATERIALS & METHODS: Astrocyte-nanofiber interactions (e.g.,
      adhesion, proliferation, process extension and migration) were studied by
      comparing human neural progenitor-derived astrocytes (hNP-ACs) and a human
      astrocytoma cell line (U373) with aligned polycaprolactone (PCL) nanofibers or
      blended (25% type I collagen/75% PCL) nanofibers. Neuron-nanofiber interactions
      were assessed using a differentiated human neuroblastoma cell line (SH-SY5Y).
      RESULTS & DISCUSSION: U373 cells and hNP-AC showed similar process alignment and
      length when associated with PCL or Type I collagen/PCL nanofibers. Cell adhesion
      and migration by hNP-AC were clearly improved by functionalization of nanofiber
      surfaces with type I collagen. Functionalized nanofibers had no such effect on
      U373 cells. Another clear difference between the U373 cells and hNP-AC
      interactions with the nanofiber substrate was proliferation; the cell line
      demonstrating strong proliferation, whereas the hNP-AC line showed no
      proliferation on either type of nanofiber. Long axonal growth (up to 600 microm
      in length) of SH-SY5Y neurons followed the orientation of both types of
      nanofibers even though adhesion of the processes to the fibers was poor.
      CONCLUSION: The use of cell lines is of only limited predictive value when
      studying cell-substrate interactions but both morphology and alignment of human
      astrocytes were affected profoundly by nanofibers. Nanofiber surface
      functionalization with collagen significantly improved hNP-AC adhesion and
      migration. Alternative forms of functionalization may be required for optimal
      axon-nanofiber interactions.

PMID- 19093895
TI  - Functionalized fluorescent nanodiamonds for biomedical applications.
AB  - In recent years, carbon and carbon-based nanomaterials have received increasing
      attention for applications in life sciences. Nanodiamond (ND) stands out as a
      unique new substance in these applications because it holds several momentous
      properties such as good biocompatibility, excellent photostability and facile
      surface functionalizability. A number of experiments have shown that ND has the
      highest biocompatibility of all carbon-based nanomaterials including carbon
      blacks, multiwalled nanotubes, single-walled nanotubes and fullerenes.
      Additionally, the surface of ND can be readily derivatized with various
      functional groups for either covalent or noncovalent conjugation with
      biomolecules. Furthermore, some radiation-damaged NDs can emit strong and stable
      photoluminescence (red or green) from nitrogen-vacancy defect centers embedded in
      the crystal lattice. These properties together make ND a highly promising
      nanomaterial for both in vitro and in vivo applications.

PMID- 19093894
TI  - On enhancers and inhibitors of elastin-derived amyloidogenesis.
AB  - AIMS: The main aim of this study is to better understand the self-aggregation
      mechanism of amyloid-like elastin-derived fibers in order to design and produce
      new powerful drugs that will inhibit the onset of 'amyloidosis'. MATERIALS &
      METHODS: Atomic force microscopy (AFM), Congo Red birefringence assay and
      Thioflavin T fluorescence measurements were used to demonstrate the amyloid-like
      behavior of some fragments of elastin protein (exon 30 [EX30] and exon 28
      [EX28]). Turbidimetry on apparent absorbance technique was used to investigate
      the effect either of enhancers or of inhibitors on the amyloidogenic elastin-like
      peptides. Circular-dichroism spectroscopy was used to study the secondary
      structures of the peptides. RESULTS & DISCUSSION: We used Congo Red birefringence
      assay, Thioflavin T fluorescence measurements and AFM measurements that are used
      commonly to demonstrate the formation of amyloids. The elastin fibrillogenesis is
      amyloid-like. Then, the elastin amyloidogenesis is inhibited by particular
      pentapeptides. CONCLUSIONS: We have reported herein that the fibrillogenesis of
      elastin-derived EX28 and EX30 polypeptides is facilitated significantly by the
      effect of sodium taurocholate bile salt and is inhibited by a classical inhibitor
      of Abeta-amyloid peptide, such as KLVFF, as well as by novel inhibitors, designed
      by us on the basis of some elastin sequences.

PMID- 19093896
TI  - Nanomaterial cell interactions: how do carbon nanotubes affect cell physiology?
AB  - Nanoparticulate materials and, among them, carbon nanotubes (CNTs) are new types
      of material that are generating high expectations owing to their unique physical,
      chemical and optical properties. Owing to the predictably increasing production
      of various types of CNTs and other nanoparticle-containing products, it is
      expected that environmental and public exposure to engineered nanoparticles will
      also increase in parallel. If and how far CNTs are able to affect health is, at
      present, discussed controversially. In this article, we summarize how CNTs are
      produced and processed to identify critical parameters, which have to be included
      in the toxicological assessment. A special effort is made to address the adverse
      effects of CNTs on cell physiology. Furthermore, we report on CNTs in medical
      applications and we discuss two selected examples of prospective applications of
      CNTs in nanomedicine, which have realistic chances of achieving ready-to-market
      products in just a few years.

PMID- 19093897
TI  - Stem cell differentiation by functionalized micro- and nanostructured surfaces.
AB  - New fabrication technologies and, in particular, new nanotechnologies have
      provided biomaterial and biomedical scientists with enormous possibilities when
      designing customized supports and scaffolds with controlled nanoscale topography
      and chemistry. The main issue now is how to effectively design these components
      and choose the appropriate combination of structure and chemistry to tailor
      towards applications as challenging and complex as stem cell differentiation.
      Occasionally, an incomplete knowledge of the fundamentals of biological
      differentiation processes has hampered this issue. However, the recent
      technological advances in creating controlled cellular microenvironments can be
      seen as a powerful tool for furthering fundamental biology studies. This article
      reviews the main strategies followed to achieve solutions to this challenge,
      particularly emphasizing the working hypothesis followed by the authors to
      elucidate the mechanisms behind the observed effects of structured surfaces on
      cell behavior.

PMID- 19093898
TI  - Inorganic nanoparticles for predictive oncology of breast cancer.
AB  - Nanoparticles (NPs) and nanosized objects are being incorporated rapidly into
      clinical medicine and particularly into the field of medical oncology, including
      breast cancer. A number of novel methods for breast cancer diagnosis and
      treatment, which are based on NPs and other nanodevices, are now available for
      translation into clinical practice. Computer tomography and MRI with iron-based
      magnetic NPs are promising methods for radiological detection of cancers.
      Semiconductor fluorescent NPs (quantum dots) are being developed for simultaneous
      detection and localization of multiple breast cancer biomarkers, enabling the
      personalization of therapeutic regimens for each patient. Additionally, inorganic
      NPs can be conjugated with tumor-specific ligands and used for tumor-selective
      delivery of chemotherapeutic or hormonal agents. NPs bearing tumor-targeted
      antibodies and oligonucleotides for anticancer gene therapy are a novel and
      rapidly developing therapeutic approach in oncology. Nab-paclitaxel and liposomal
      anthracyclines are US FDA-approved NP-based drug-delivery systems that have
      demonstrated at least equivalent efficacy and decreased toxicity compared with
      conventional chemotherapeutic agents used in the treatment of breast cancer. This
      review focuses on recent applications of NPs into predictive oncology of breast
      cancer with an emphasis placed on the role of inorganic nanosized objects in the
      diagnosis and treatment of this malignancy.

PMID- 19093899
TI  - Targeted nanomedicines: effective treatment modalities for cancer, AIDS and brain
      disorders.
AB  - Novel technology in the nanomedicine field is expected to develop innovative
      products as targeted drug-delivery approaches. Targeted drug delivery of various
      drugs for the treatment of cancer, AIDS and brain disorders is the primary
      research area in which nanomedicines have a major role and need. This review is
      concerned with emerging targeted nanomedicines (polymeric nanoparticles, solid
      lipid nanoparticles, polymeric micelles, dendrimers, liposomes, gold
      nanoparticles and magnetic nanoparticles) and multifunctional carriers capable of
      combining targeted drug delivery and imaging (polymeric micelles, dendrimers and
      magnetic nanoparticles) in the field of pharmaceutical applications. The
      significant toxicity issues associated with these nanomedicines are also explored
      here.

PMID- 19093901
TI  - A biomechanical comparison of two patterns of screw insertion.
AB  - Inserting a screw into a long bone introduces a stress riser that can predispose
      the bone to fracture. Where multiple screws are inserted this vulnerability may
      be increased. It is thought that the pattern of screw insertion plays an
      important part in determining the susceptibility of the bone to stress fracture.
      In order to study the importance of pattern of screw insertion, third generation
      composite femora with cannulated screws inserted in two different patterns were
      tested to failure by a servohydraulic materials test system. The vertical pattern
      of screw insertion is less apt to predispose a long bone to subsequent fracture
      than a horizontal pattern.

PMID- 19093902
TI  - Effect of specialty and experience on the interpretation of knee MRI scans.
AB  - The purpose of this study was to evaluate any differences in the accuracy of knee
      MRI interpretation between radiology and orthopaedic surgery residents as well as
      to evaluate differences in quality of interpretation relative to resident
      training level. In this study, 20 MRI scans demonstrating specific pathology of
      the knee were identified. From one institution, two radiology residents and two
      orthopaedic surgery residents of each postgraduate year (PGY) of training (2 to
      5) were recruited. Each resident was asked to interpret all the studies and
      choose up to 16 diagnoses for each scan from the list provided. Orthopaedic
      surgery residents showed improvement in overall accuracy and specificity with
      each year of additional training. Level of training did not correspond with
      increased sensitivity in the orthopaedic residents tested. Radiology residents
      did not demonstrate a consistent trend toward improved accuracy, sensitivity, or
      specificity with additional years of training. The only statistically significant
      differences in specificity observed between the two groups were seen in the
      readings of ACL tears, lateral femoral condyle chondromalacia, and chondromalacia
      patella. This study found that the accuracy of knee MRI interpretations between
      radiology and orthopaedic surgery residents did not demonstrate any differences.
      Level of training had no effect on the interpretation of the MRIs by radiology
      residents. Orthopaedic surgery residents did show an improvement with each year
      of additional training.

PMID- 19093903
TI  - Treatment of trochanteric fractures with the PFNA (proximal femoral nail
      antirotation) nail system - report of early results.
AB  - Currently, intramedullary devices are widely used for the treatment of
      trochanteric femoral fractures. A new device designed by AO/ASIF, the PFNA
      (proximal femoral nail antirotation), represents a unique intramedullary nail
      system for improved management, particularly in the elderly. The aim of the
      present study was to analyze the results of treatment with PFNA in 50 patients
      with trochanteric fractures. The operating time, intraoperative blood loss, and
      intraoperative and postoperative complications were recorded. The length of the
      surgical procedure averaged 20.3 min, and intraoperative blood loss averaged 22.8
      mL. Reoperation was necessary in two patients (4%). We conclude that the PFNA
      nail is as effective as other implants in the treatment of trochanteric
      fractures.

PMID- 19093904
TI  - Does anti-TNF-alpha have a role in the treatment of osteoporosis?

PMID- 19093905
TI  - Does hospital surgical volume affect in-hospital outcomes in surgically treated
      pelvic and acetabular fractures?
AB  - A retrospective evaluation was done to determine the relationship between
      hospital volume and in-hospital mortality, complications, and length of stay in
      patients with operatively treated fractures of the pelvis or acetabulum. Patients
      were divided into three groups based on hospital volume. High volume centers had
      higher percentages of patients with one or more comorbidities, but who were less
      severely injured. Mortality rates were highest in small volume centers. Moderate
      volume centers had the lowest odds of death. Complication rates were similar
      between small and high volume hospitals. Length of stay was shortest in high
      volume centers. In-hospital outcomes associated with surgical fixation of the
      pelvis, acetabulum, or both were not uniformly associated with hospital volume.

PMID- 19093906
TI  - Risk of injury associated with the use of seat belts and air bags in motor
      vehicle crashes.
AB  - Although air bags have been reported to reduce passenger mortality in frontal
      collisions, they have also been reported as a cause of injury in motor vehicle
      collisions(MVCs). The purpose of this study was to evaluate a large cohort of
      patients involved in MVCs to determine mortality and the pattern of injuries
      associated with seat belt use and air bag deployment. Information on patients
      involved in MVCs from 1988 to 2004 was obtained from the National Trauma Data
      Bank (NTDB). The data was evaluated based on four groups of safety devices: seat
      belt and deployed air bag (SBAB), seat belt only (SBO), deployed air bag only
      (ABO), and no safety devices (None). A total of 35,333 patients met study
      inclusion criteria. Air bags and seat belts used in combination decreased the
      risk of potentially fatal injuries, but increased the risk of lower extremity
      injuries (odds ratio, 1.35). The use of any type of restraint led to a decrease
      in the risk of injury or mortality in MVCs. Only half of all individuals in this
      study used any type of restraint device, which indicates the need for significant
      improvements in public health and safety seat belt utilization programs.

PMID- 19093907
TI  - Orthopaedic anesthesia - part 1. Commonly used anesthetic agents in orthopaedics.
AB  - Anesthesia is a broad discipline; for orthopaedic applications, the type and
      location of the planned orthopaedic procedure is important in the selection of
      the most appropriate anesthetic agent and technique. The purpose of this overview
      is to: 1. highlight the role of several anesthetic agents commonly used in an
      orthopaedic setting and 2. to familiarize the orthopaedist with those techniques
      of regional anesthesia that have implications for emergency rooms and other
      ambulatory settings. Because the subject matter is expansive in scope, it is
      necessary to address each of the above objectives separately, in two different
      articles. Part 1 describes anesthetic agents, whereas Part 2 encompasses
      techniques of administering regional anesthesia.

PMID- 19093908
TI  - Orthopaedic anesthesia - part 2. Common techniques of regional anesthesia in
      orthopaedics.
AB  - Anesthesia may be considered in terms of two categories: general and regional.
      The aim of general anesthesia is to induce analgesia, sedation, amnesia,
      suppression of autonomic reflexes, and relaxation of muscles. Regional anesthesia
      is more site-specific and is typically divided into three categories based on the
      location of injection: 1. a central neuraxial block is an injection of an
      anesthetic drug into the epidural or intrathecal space; 2. a peripheral nerve
      block is an injection near the nerve or plexus supplying the area under
      operation; and 3. a field block is an injection into the adjoining tissues with
      subsequent diffusion into the surgical area (in orthopaedics, it is typically
      employed for minor procedures of the hand or foot). Of these three categories of
      regional anesthesia (i.e., neuraxial, peripheral, and field blocks), this article
      focuses on the latter two. Although neuraxial blocks comprise an important part
      of regional anesthesia, they are typically performed by anesthesiologists in an
      operative setting for major procedures of the lower extremities. The intent of
      this article is to familiarize the orthopaedist with techniques that have
      implications for emergency rooms and other ambulatory settings in which regional
      techniques are sometimes favored over general alternatives because they entail
      less risk of systemic side effects and may involve more cost-effective use of
      resources.

PMID- 19093909
TI  - The chessboard technique - a new freehand aiming method for rapid distal locking
      of tibial nails.
AB  - Distal locking is considered a difficult stage of the endomedullary tibial
      nailing procedure. A new rapid, simple, and inexpensive freehand aiming technique
      is presented that uses a galvanized metal grid. The grid is positioned to overlay
      the skin of the medial cutaneous face of the tibia, giving to the underlying bone
      under fluoroscopy a pattern that resembles a chessboard. The squares of the grid
      permit a rapid and accurate localization of the corresponding distal holes of the
      endomedullary nail, requiring only a single fluoroscopy image, which can be
      important relative to radiation exposure.

PMID- 19093910
TI  - Asymmetric bilateral hip dislocation after motor vehicle accident - a case study
      and review of the literature.
AB  - Bilateral asymmetric dislocations of the hip are rare compared to unilateral
      dislocations. This case study describes a female restrained passenger involved in
      a motor vehicle accident who sustained asymmetric bilateral hip dislocations. The
      patient underwent successful closed reduction of both hips. The clinical course
      and follow-up assessment of the patient was otherwise uneventful. Computed
      tomography scans, essential for diagnosing intra-articular loose bodies and
      subtle fractures, were performed after reduction and revealed in the right hip a
      nondisplaced acetabular rim fracture of the posterior wall on the side of the
      posterior dislocation. Hip dislocations are an injury requiring careful trauma
      evaluation to rule out concomitant injuries. Time to presentation and, more
      importantly, reduction of a hip dislocation, is essential in treating this injury
      and preventing long-term complications, such as avascular necrosis and
      posttraumatic arthritis. The incidence, anatomy, mechanism of injury, treatment
      options, and long-term sequelae of hip dislocation, with literature review, are
      discussed.

PMID- 19093911
TI  - Complete anaesthesia in the cutaneous distribution of the ulnar nerve following
      submuscular anterior transposition - a case report.
AB  - Complete anaesthesia in the cutaneous distribution of the ulnar nerve following
      submuscular anterior transposition of the ulnar nerve has not been previously
      reported. We postulate vascular insult as the etiology of this condition and
      suggest there may be clinical importance to preserving the ulnar nerve blood
      supply during submuscular anterior transposition.

PMID- 19093912
TI  - Biology of the Cell: serving the cell biology community.

PMID- 19093913
TI  - A haemagglutinin from the medicinal fungus Cordyceps militaris.
AB  - There are only a few reports on agglutinins from ascomycete and medicinal fungi.
      An HA (haemagglutinin), with an N-terminal amino acid sequence different from
      those of known lectins, was isolated in the present study from dried fruiting
      bodies of the medicinal ascomycete fungus Cordyceps militaris. The purification
      protocol consisted of affinity chromatography, ion-exchange chromatography and
      gel filtration. The haemagglutinating activity of the HA could not be inhibited
      by simple sugars or heparin, and was stable over the pH range 2-13 and up to 60
      degrees C. Chemical modification of tryptophan and tyrosine residues had no
      effect. The HA exhibited some antiproliferative activity towards hepatoma (HepG2)
      cells and inhibited HIV-1 reverse transcriptase (IC50=10 microM). However, it did
      not exhibit antifungal activity, mitogenic activity towards splenocytes, nitric
      oxide-inducing activity towards macrophages or RNase activity. The results of the
      present study add to the meagre information pertaining to agglutinins from
      ascomycete and medicinal mushrooms. It is revealed in this study that C.
      militaris HA differs from other ascomycete mushroom HAs in a variety of
      biochemical characteristics.

PMID- 19093914
TI  - Intramyocellular lipid levels are associated with peripheral, but not hepatic,
      insulin sensitivity in normal healthy subjects.
AB  - Increased levels of IMCL (intramyocellular lipid) have been shown to be
      associated with reduced steady-state glucose infusion rates during a
      hyperinsulinaemic-euglycaemic clamp (M-value). The aim of the present study was
      to explore how IMCL levels relate to the insulin-mediated suppression of
      endogenous glucose production [hepatic SI (insulin sensitivity)] and increase in
      glucose disposal (peripheral SI). In the present study, 11 healthy young adults
      (7 male, 4 female; aged 21-31 years) undertook, in random order, an
      hyperinsulinaemic-euglycaemic clamp combined with stable glucose isotope
      enrichment to measure peripheral and hepatic SI, a 1H-MRS (proton-magnetic
      resonance spectroscopy) scan to determine IMCL levels and a DXA (dual-energy X
      ray absorptiometry) scan to assess body composition. IMCL levels (range, 3.2
      10.7) were associated with whole-body fat mass (r=0.787, P=0.004), fat mass
      corrected for height (r=0.822, P=0.002) and percentage of central fat mass
      (r=0.694, P=0.02), but were not related to whole-body FFM (fat-free mass; r=
      0.472, P=0.1). IMCL levels correlated closely with the M-value (r=-0.727, P=0.01)
      and FFM-corrected peripheral SI (r=-0.675, P=0.02), but were not related to
      hepatic SI adjusted for body weight (r=0.08, P=0.8). The results of the present
      study suggest that IMCL accumulation may be a sensitive marker for attenuations
      in peripheral, but not hepatic, SI in normal populations. Given the close
      relationship of IMCL levels to whole-body and central abdominal fat mass,
      relative increases in the flux of lipids from adipose tissue to the
      intramyocellular compartment may be an integral part of the mechanisms underlying
      reductions in SI.

PMID- 19093915
TI  - Recovery of activities of daily living in older adults after hospitalization for
      acute medical illness.
AB  - OBJECTIVES: To compare functional outcomes in the year after discharge for older
      adults discharged from the hospital after an acute medical illness with a new or
      additional disability in their basic self-care activities of daily living (ADL)
      (compared with preadmission baseline 2 weeks before admission) with those of
      older adults discharged with baseline ADL function and identify predictors of
      failure to recover to baseline function 1 year after discharge. DESIGN:
      Observational. SETTING: Tertiary care hospital, community teaching hospital.
      PARTICIPANTS: Older (aged >or=70) patients nonelectively admitted to general
      medical services (1993-1998). MEASUREMENTS: Number of ADL disabilities at
      preadmission baseline and 1, 3, 6, and 12 months after discharge. Outcomes were
      death, sustained decline in ADL function, and recovery to baseline ADL function
      at each time point. RESULTS: By 12 months after discharge, of those discharged
      with new or additional ADL disability, 41.3% died, 28.6% were alive but had not
      recovered to baseline function, and 30.1% were at baseline function. Of those
      discharged at baseline function, 17.8% died, 15.2% were alive but with worse than
      baseline function, and 67% were at their baseline function (P<.001). Of those
      discharged with new or additional ADL disability, the presence or absence of
      recovery by 1 month was associated with long-term outcomes. Age, cardiovascular
      disease, dementia, cancer, low albumin, and greater number of dependencies in
      instrumental ADLs independently predicted failure to recover. CONCLUSION: For
      older adults discharged with new or additional disability in ADL after
      hospitalization for medical illness, prognosis for functional recovery is poor.
      Rehabilitation interventions of longer duration and timing than current
      reimbursement allows, caregiver support, and palliative care should be evaluated.

PMID- 19093916
TI  - Area-level poverty is associated with greater risk of ambulatory-care-sensitive
      hospitalizations in older breast cancer survivors.
AB  - OBJECTIVES: To estimate the frequency of ambulatory care-sensitive
      hospitalizations (ACSHs) and to compare the risk of ACSH in breast cancer
      survivors living in high-poverty with that of those in low-poverty areas. DESIGN:
      Prospective, multilevel study. SETTING: National, population-based 1991 to 1999
      National Cancer Institute Surveillance, Epidemiology, and End Results Program
      data linked with Medicare claims data throughout the United States. PARTICIPANTS:
      Breast cancer survivors aged 66 and older. MEASUREMENTS: ACSH was classified
      according to diagnosis at hospitalization. The percentage of the population
      living below the U.S. federal poverty line was calculated at the census-tract
      level. Potential confounders included demographic characteristics, comorbidity,
      tumor and treatment factors, and availability of medical care. RESULTS: Of 47,643
      women, 13.3% had at least one ACSH. Women who lived in high-poverty census tracts
      (>or=30% poverty rate) were 1.5 times (95% confidence interval (CI)=1.34-1.72) as
      likely to have at least one ACSH after diagnosis as women who lived in low
      poverty census tracts (<10% poverty rate). After adjusting for most confounders,
      results remained unchanged. After adjustment for comorbidity, the hazard ratio
      (HR) was reduced to 1.34 (95% CI=1.18-1.52), but adjusting for all variables did
      not further reduce the risk of ACSH associated with poverty rate beyond
      adjustment for comorbidity (HR=1.37, 95% CI=1.19-1.58). CONCLUSION: Elderly
      breast cancer survivors who lived in high-poverty census tracts may be at
      increased risk of reduced posttreatment follow-up care, preventive care, or
      symptom management as a result of not having adequate, timely, and high-quality
      ambulatory primary care as suggested by ACSH.

PMID- 19093917
TI  - Effect of physical activity counseling on disability in older people: a 2-year
      randomized controlled trial.
AB  - OBJECTIVES: To study the effect of a physical activity counseling intervention on
      instrumental activity of daily living (IADL) disability. DESIGN: Primary care
      based, single-blind, randomized controlled trial. SETTING: City of Jyvaskyla,
      central Finland. PARTICIPANTS: Six hundred thirty-two people aged 75 to 81 who
      were able to walk 500 meters without assistance, were at most moderately
      physically active, had a Mini-Mental State Examination score greater than 21, had
      no medical contraindications for physical activity, and gave informed consent for
      participation. INTERVENTION: A single individualized physical activity counseling
      session with supportive phone calls from a physiotherapist every 4 months for 2
      years and annual lectures on physical activity. Control group received no
      intervention. MEASUREMENTS: The outcome was IADL disability defined as having
      difficulties in or inability to perform IADL tasks. Analyses were carried out
      according to baseline IADL disability, mobility limitation, and cognitive status.
      RESULTS: At the end of the follow-up, IADL disability had increased in both
      groups (P<.001) and was lower in the intervention group, but the group-by-time
      interaction effect did not reach statistical significance. Subgroup analyses
      revealed that the intervention prevented incident disability in subjects without
      disability at baseline (risk ratio=0.68, 95% confidence interval=0.47-0.97) but
      had no effect on recovery from disability. CONCLUSION: The physical activity
      counseling intervention had no effect on older sedentary community-dwelling
      persons with a wide range of IADL disability, although it prevented incident IADL
      disability. The results warrant further investigation to explore the benefits of
      a primary care-based physical activity counseling program on decreasing and
      postponing IADL disability.

PMID- 19093918
TI  - Cumulative anticholinergic exposure is associated with poor memory and executive
      function in older men.
AB  - OBJECTIVES: To examine the longitudinal relationship between cumulative exposure
      to anticholinergic medications and memory and executive function in older men.
      DESIGN: Prospective cohort study. SETTING: A Department of Veterans Affairs
      primary care clinic. PARTICIPANTS: Five hundred forty-four community-dwelling men
      aged 65 and older with diagnosed hypertension. MEASUREMENTS: The outcomes were
      measured using the Hopkins Verbal Recall Test (HVRT) for short-term memory and
      the instrumental activity of daily living (IADL) scale for executive function at
      baseline and during follow-up. Anticholinergic medication use was ascertained
      using participants' primary care visit records and quantified as total
      anticholinergic burden using a clinician-rated anticholinergic score. RESULTS:
      Cumulative exposure to anticholinergic medications over the preceding 12 months
      was associated with poorer performance on the HVRT and IADLs. On average, a 1
      unit increase in the total anticholinergic burden per 3 months was associated
      with a 0.32-point (95% confidence interval (CI)= 0.05-0.58) and 0.10-point (95%
      CI=0.04-0.17) decrease in the HVRT and IADLs, respectively, independent of other
      potential risk factors for cognitive impairment, including age, education,
      cognitive and physical function, comorbidities, and severity of hypertension. The
      association was attenuated but remained statistically significant with memory
      (0.29, 95% CI=0.01-0.56) and executive function (0.08, 95% CI=0.02-0.15) after
      further adjustment for concomitant non-anticholinergic medications. CONCLUSION:
      Cumulative anticholinergic exposure across multiple medications over 1 year may
      negatively affect verbal memory and executive function in older men. Prescription
      of drugs with anticholinergic effects in older persons deserves continued
      attention to avoid deleterious adverse effects.

PMID- 19093919
TI  - The effect of technology-supported, multidisease care management on the mortality
      and hospitalization of seniors.
AB  - OBJECTIVES: To explore changes in mortality and hospital usage for chronically
      ill seniors enrolled in a multidisease care management program, Care Management
      Plus (CMP). DESIGN: Controlled clinical trial with seven intervention and six
      control clinics with additional patient-level matching. SETTING: Intermountain
      Health Care, a large health system in Utah; seven intervention and six control
      clinics. PARTICIPANTS: Three thousand four hundred thirty-two senior patients
      (>or=65) enrolled in Medicare. INTERVENTION: The intervention employed nurse care
      managers supported by specialized information technology in primary care to
      manage chronically ill patients (2002-2005). MEASUREMENTS: Mortality and
      hospitalization data were collected from clinical records and Medicare billing.
      RESULTS: One thousand one hundred forty-four intervention patients were matched
      to 2,288 controls. Average age was 76.2; average comorbidity score was 2.3+/-1.1;
      75% of patients had two or more chronic diseases. Survival analyses showed lower
      mortality and slightly more emergency department visits for care managed patients
      than for controls. In patients with diabetes mellitus, the intervention resulted
      in significantly lower mortality at 1 year (6.2%, vs 10.6% for controls) and at 2
      years (12.9% vs 18.2%). Hospitalization rate was lower (21.0%, vs. 24.2% for
      controls) at 1 year and substantially more so at the 2-year follow-up.
      CONCLUSION: CMP was successful in reducing death for all patients. For complex
      patients with diabetes mellitus in the intervention group, death and hospital
      usage were lower. Per clinic, hypothesized savings from decreased
      hospitalizations was $17,384 to $70,349.

PMID- 19093920
TI  - Prognostic significance of potential frailty criteria.
AB  - OBJECTIVES: To determine the independent prognostic effect of seven potential
      frailty criteria, including five from the Fried phenotype, on several adverse
      outcomes. DESIGN: Prospective cohort study. SETTING: Greater New Haven,
      Connecticut. PARTICIPANTS: Seven hundred fifty-four initially nondisabled,
      community-living persons aged 70 and older. MEASUREMENTS: An assessment of seven
      potential frailty criteria (slow gait speed, low physical activity, weight loss,
      exhaustion, weakness, cognitive impairment, and depressive symptoms) was
      completed at baseline and every 18 months for 72 months. Participants were
      followed with monthly telephone interviews for up to 96 months to determine the
      occurrence of chronic disability, long-term nursing home (NH) stays, injurious
      falls, and death. RESULTS: In analyses adjusted for age, sex, race, education,
      number of chronic conditions, and the presence of the other potential frailty
      criteria, three of the five Fried criteria (slow gait speed, low physical
      activity, and weight loss) were independently associated with chronic disability,
      long-term NH stays, and death. Slow gait speed was the strongest predictor of
      chronic disability (hazard ratio (HR)=2.97, 95% confidence interval (CI)=2.32
      3.80) and long-term NH stay (HR=3.86, 95% CI=2.23-6.67) and was the only
      significant predictor of injurious falls (HR=2.19, 95% CI=1.33-3.60). Cognitive
      impairment was also associated with chronic disability (HR=1.82, 95% CI=1.40
      2.38), long-term NH stay (HR=2.64, 95% CI=1.75-3.99), and death (HR=1.54, 95%
      CI=1.13-2.10), and the magnitude of these associations was comparable with that
      of weight loss. CONCLUSION: The results of this study provide strong evidence to
      support the use of slow gait speed, low physical activity, weight loss, and
      cognitive impairment as key indicators of frailty while raising concerns about
      the value of self-reported exhaustion and muscle weakness.

PMID- 19093921
TI  - Does low to moderate alcohol intake protect against cognitive decline in older
      people?
AB  - OBJECTIVES: To determine whether low to moderate alcohol intake is protective
      against cognitive decline in older people. DESIGN: Prospective cohort study.
      SETTING: Community-based study in Ireland, the Netherlands, and Scotland.
      PARTICIPANTS: Five thousand eight hundred four people (3,000 women) aged 70 to 82
      and randomized to pravastatin or placebo in the Prospective Study of Pravastatin
      in the Elderly at Risk. MEASUREMENTS: Alcohol consumption was determined at study
      baseline. Serial measures of cognitive function over 3.2 years mean follow-up
      included Mini-Mental-State-Examination (MMSE), speed of information processing
      (Stroop and Letter-Digit Coding tests), and immediate and delayed memory (Picture
      Word Learning test). RESULTS: Forty-two percent of women and 71% of men were
      alcohol drinkers. Cognitive performance was better for female drinkers than
      nondrinkers for all cognitive domains over the 3.2-year follow-up; no significant
      effects were seen for men (linear mixed model, including adjusting for possible
      confounders). The rate of cognitive decline was similar for drinkers and
      nondrinkers for all cognitive domains, except for MMSE, which declined
      significantly less in female drinkers than nondrinkers (linear mixed model
      attenuated rate of decline=0.05 MMSE units per annum, P=.001). CONCLUSION:
      Drinking low to moderate amounts of alcohol may delay age-associated cognitive
      decline in older women (including slowing deterioration in global cognitive
      function), but these apparent benefits were not clearly seen in older men.

PMID- 19093922
TI  - Effect of computerized provider order entry with clinical decision support on
      adverse drug events in the long-term care setting.
AB  - OBJECTIVES: To evaluate the efficacy of computerized provider order entry with
      clinical decision support for preventing adverse drug events in long-term care.
      DESIGN: Cluster-randomized controlled trial. SETTING: Two large long-term care
      facilities. PATIENTS: One thousand one hundred eighteen long-term care residents
      of 29 resident care units. INTERVENTION: The 29 resident care units, each with
      computerized provider order entry, were randomized to having a clinical decision
      support system (intervention units) or not (control units). MEASUREMENTS: The
      number of adverse drug events, severity of events, and whether the events were
      preventable. RESULTS: Within intervention units, 411 adverse drug events occurred
      over 3,803 resident-months of observation time; 152 (37.0%) were deemed
      preventable. Within control units, there were 340 adverse drug events over 3,257
      resident-months of observation time; 126 (37.1%) were characterized as
      preventable. There were 10.8 adverse drug events per 100 resident-months and 4.0
      preventable events per 100 resident-months on intervention units. There were 10.4
      adverse drug events per 100 resident-months and 3.9 preventable events per 100
      resident-months on control units. Comparing intervention and control units, the
      adjusted rate ratios were 1.06 (95% confidence interval (CI)=0.92-1.23) for all
      adverse drug events and 1.02 (95% CI=0.81-1.30) for preventable adverse drug
      events. CONCLUSION: Computerized provider order entry with decision support did
      not reduce the adverse drug event rate or preventable adverse drug event rate in
      the long-term care setting. Alert burden, limited scope of the alerts, and a need
      to more fully integrate clinical and laboratory information may have affected
      efficacy.

PMID- 19093923
TI  - Effective exercise for the prevention of falls: a systematic review and meta
      analysis.
AB  - OBJECTIVES: To determine the effects of exercise on falls prevention in older
      people and establish whether particular trial characteristics or components of
      exercise programs are associated with larger reductions in falls. DESIGN:
      Systematic review with meta-analysis. Randomized controlled trials that compared
      fall rates in older people who undertook exercise programs with fall rates in
      those who did not exercise were included. SETTING: Older people. PARTICIPANTS:
      General community and residential care. MEASUREMENTS: Fall rates. RESULTS: The
      pooled estimate of the effect of exercise was that it reduced the rate of falling
      by 17% (44 trials with 9,603 participants, rate ratio (RR)=0.83, 95% confidence
      interval (CI)=0.75-0.91, P<.001, I(2)=62%). The greatest relative effects of
      exercise on fall rates (RR=0.58, 95% CI=0.48-0.69, 68% of between-study
      variability explained) were seen in programs that included a combination of a
      higher total dose of exercise (>50 hours over the trial period) and challenging
      balance exercises (exercises conducted while standing in which people aimed to
      stand with their feet closer together or on one leg, minimize use of their hands
      to assist, and practice controlled movements of the center of mass) and did not
      include a walking program. CONCLUSION: Exercise can prevent falls in older
      people. Greater relative effects are seen in programs that include exercises that
      challenge balance, use a higher dose of exercise, and do not include a walking
      program. Service providers can use these findings to design and implement
      exercise programs for falls prevention.

PMID- 19093924
TI  - Neutrophils of centenarians show function levels similar to those of young
      adults.
AB  - OBJECTIVES: To analyze several functions and antioxidant parameters of peripheral
      blood neutrophils from healthy centenarians (men and women) and compare them with
      those of healthy young (aged 25-35) and middle-aged (aged 65-75) men and women.
      DESIGN: Cross-sectional study. SETTING: Community-based. PARTICIPANTS: Twenty-one
      healthy centenarians (8 men), 30 young adults (15 men), and 30 middle-aged adults
      (15 men). MEASUREMENTS: Several neutrophil functions (adherence, chemotaxis,
      phagocytosis, and stimulated and nonstimulated intracellular superoxide anion
      levels) and antioxidant parameters (glutathione levels and catalase activity)
      were measured in peripheral blood neutrophil suspension in the three study
      groups. RESULTS: Neutrophil functions of the middle-aged group were worse than
      those of young adults and centenarians (lower chemotaxis and phagocytosis and
      higher adherence and superoxide anion levels). The neutrophil functions of the
      centenarians were closer to those of the young adults. Age-related differences in
      neutrophil functions were fundamentally similar in men and women, except for
      intracellular superoxide anion levels, which were lower in young adult women than
      in young adult men. With normal aging, total glutathione levels decrease, but the
      centenarians in this study showed levels similar to those of young adults.
      Centenarians showed the highest catalase activity of the three groups.
      CONCLUSION: Progressive impairment of the immune system accompanies aging. The
      better preservation of function and antioxidant systems in the neutrophils of
      centenarians could play a key role in the longevity of these subjects.

PMID- 19093925
TI  - Overweight and obesity in old age are not associated with greater dementia risk.
AB  - OBJECTIVES: To describe the association between body mass index (BMI) and
      dementia risk in older persons. DESIGN: Prospective population-based study, with
      8 years of follow-up. SETTING: The municipality of Lieto, Finland, 1990/91 and
      1998/99. PARTICIPANTS: Six hundred five men and women without dementia aged 65 to
      92 at baseline (mean age 70.8). MEASUREMENTS: Weight and height were measured at
      baseline and at the 8-year follow-up. Dementia was clinically assessed according
      to Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition,
      criteria. RESULTS: Eighty-six persons were diagnosed with dementia. Cox
      regression analyses, adjusted for age, sex, education, cardiovascular diseases,
      smoking, and alcohol use, indicated that, for each unit increase in BMI score,
      the risk of dementia decreased 8% (hazard ratio (HR)=0.92, 95% confidence
      interval (CI)=0.87-0.97). This association remained significant when individuals
      who developed dementia early during the first 4 years of follow-up were excluded
      from the analyses (HR=0.93, 95% CI=0.86-0.99). Women with high BMI scores had a
      lower dementia risk (HR=0.90, 95% CI=0.84-0.96). Men with high BMI scores also
      tended to have a lower dementia risk, although the association did not reach
      significance (HR=0.95, 95% CI=0.84-1.07). CONCLUSION: Older persons with higher
      BMI scores have less dementia risk than their counterparts with lower BMI scores.
      High BMI scores in late life should not necessarily be considered to be a risk
      factor for dementia.

PMID- 19093926
TI  - Death certificate inaccuracy and underreporting of injury in elderly people.
AB  - OBJECTIVES: To assess whether resident physicians (MDs) could complete a death
      certificate for elderly patients with injury-related fatalities and whether their
      abilities were related to training or other factors. SETTING: A large tertiary
      teaching hospital in Boston, Massachusetts. PARTICIPANTS: Three hundred thirty
      six MDs. DESIGN: Through an anonymous Web-based test, MDs were questioned
      regarding prior training and experience in completion of death certificates. The
      MDs read a case of an elderly patient who died from intracranial bleeding after a
      fall and then completed a test death certificate. Whether proper completion was
      associated with MD characteristics such as year of residency, self-assessment, or
      previous death certificate experience was examined. RESULTS: Almost two-thirds
      (63.6%) of MDs completed the test. Of participants, 52% (95% confidence interval
      (CI)=46-59%) filled out the death certificate with the correct primary cause of
      death and 10% (95% CI=6-14%) listed the three major contributing causes of death.
      Only 35% (95% CI=28-41%) correctly reported injury as a contributing cause of
      death, but 51% of the participants reported a high level of confidence in their
      ability to complete a death certificate accurately. CONCLUSION: Accurate
      completion of the sample death certificate and identification of injury was low,
      and MDs overrated their abilities. Death certificates completed by MDs may not be
      accurate and may underestimate the contribution of injury to elderly mortality.

PMID- 19093927
TI  - Predictors of in-hospital and long-term clinical outcome in elderly patients with
      massive pulmonary embolism receiving thrombolytic therapy.
AB  - OBJECTIVES: To determine the clinical, historical, and instrumental findings
      associated with unfavorable short-term and long-term prognosis in elderly
      patients (>or=65) receiving thrombolytic therapy for pulmonary embolism (PE).
      DESIGN: Case-control retrospective study. SETTING: General medicine acute care
      ward. PARTICIPANTS: Sixty-seven elderly patients with PE complicated by
      hemodynamic instability (massive PE) admitted to the "Antonio Cardarelli"
      Hospital from January 1, 2002, to December 31, 2004, and evaluated during their
      hospital stay and 174.4+/-4.6 days after discharge. MEASUREMENTS: PE diagnosis
      was confirmed using spiral computed tomography angiography. Hemodynamic
      instability was defined as cardiogenic shock and systolic blood pressure less
      than 90 mmHg or a pressure drop of 40 mmHg or more for longer than 15 minutes not
      due to new-onset arrhythmia, hypovolemia, or sepsis. INTERVENTION: Weight-adapted
      unfractionated heparin and recombinant tissue plasminogen activator. RESULTS:
      Nine patients (13.4%) died during hospitalization. Higher troponin-I (cTn-I)
      serum levels at admission to the emergency department and the occurrence of
      thrombocytopenia after thrombolysis were significantly associated with in
      hospital death. Nineteen of the 58 survivors (32.7%) died during follow-up. The
      risk factors for long-term death were historical findings of cancer and
      cardiovascular disease at hospital admission. CONCLUSION: Higher cTn-I serum
      levels in the acute phase and the occurrence of thrombocytopenia after
      thrombolysis were significantly associated with in-hospital mortality in elderly
      patients with massive PE. In the same setting, historical findings of cancer and
      cardiovascular disease are strong predictors of death in the long term.

PMID- 19093928
TI  - Sustained benzodiazepine use in a community sample of older adults.
AB  - OBJECTIVES: To identify factors associated with sustained benzodiazepine use in
      older adults. DESIGN: Twelve-year cohort study. SETTING: Community-based
      epidemiological survey. PARTICIPANTS: One thousand three hundred forty-two
      individuals aged 65 and older. MEASUREMENTS: Demographics, medication use,
      depressive symptoms, sleep complaints, alcohol use, and smoking assessed at 2
      year intervals; descriptive analysis to characterize benzodiazepine users and
      identify factors associated with sustained benzodiazepine use (use at two
      consecutive waves); and longitudinal lag-time analysis to determine
      characteristics that predicted sustained use. RESULTS: Initially, 5.5% of men and
      9.8% of women were using benzodiazepines. Users were significantly more likely
      than nonusers to be female and less educated, report more depressive and anxiety
      symptoms, use more prescription medications, have lower self-rated health, have
      difficulty maintaining sleep, and be less likely to consume alcohol.
      Approximately 50%, 44%, and 25% of these users aged 65 to 74, 75 to 84, and 85
      and older, respectively, were sustained users at follow-up. Being female, using
      two or more nonbenzodiazepine prescription medications, and smoking were
      independently associated with subsequent sustained benzodiazepine use.
      CONCLUSION: At the population level, women, smokers, and users of at least two
      prescription drugs have higher probabilities of sustaining benzodiazepine use
      once started. This information can facilitate risk assessment and counseling of
      older adults before prescribing benzodiazepines.

PMID- 19093929
TI  - The aggressive behavior scale: a new scale to measure aggression based on the
      minimum data set.
AB  - OBJECTIVES: To examine the reliability and validity of the Aggressive Behavior
      Scale (ABS), derived from the Minimum Data Set (MDS 2.0). DESIGN: Retrospective
      analysis of MDS 2.0 and Cohen Mansfield Agitation Inventory (CMAI) data. SETTING:
      Ontario nursing homes (NHs) and complex continuing care (CCC) hospitals and
      units. PARTICIPANTS: Two hundred fourteen patients of a CCC hospital, 652
      residents of four NH facilities who adopted the MDS 2.0 before its mandatory
      implementation, 124,259 CCC patients assessed with the MDS 2.0 between July 1996
      and October 2006. MEASUREMENTS: In all samples, trained facility clinical staff
      completed the MDS 2.0 as part of normal clinical practice. The ABS is a 4-item
      summary scale measuring verbal and physical abuse, socially inappropriate
      behavior, and resisting care. In the single CCC facility, clinical facility staff
      completed the CMAI during the same assessment period as the MDS 2.0. RESULTS:
      Alphas for the ABS were between 0.79 and 0.93 for the three samples. A strong
      relationship was found between the ABS and the aggressive subscale of the CMAI
      (correlation coefficient=0.72, P<.001). Impairment in cognition was found to be
      related to higher ABS scores in all three samples. In CCC, individuals who had
      higher ABS scores also had a higher prevalence of psychiatric diagnoses and
      greater frequency of daily restraint use (P<.001 for each dependent variable).
      CONCLUSION: The ABS provides a useful measure of the severity of aggressive
      behavior that can be used for care planning, quality measurement, and research.

PMID- 19093930
TI  - The effect of transitioning to medicare part d drug coverage in seniors dually
      eligible for medicare and medicaid.
AB  - OBJECTIVES: To evaluate medication use, out-of-pocket spending, and medication
      switching during the transition period for patients dually eligible for Medicaid
      and Medicare (dual eligibles). DESIGN: Time-trend analysis, using segmented
      linear regression. SETTING: Patient-level pharmacy dispensing data from January
      2005 to December 2006 from a large pharmacy chain with stores in 34 states.
      PARTICIPANTS: Dual eligibles aged 65 and older. MEASUREMENTS: Changes in
      utilization, patient copayments, and medication switching were analyzed using
      interrupted time trend analyses. Utilization and spending were evaluated for five
      study drugs: clopidogrel, proton pump inhibitors (PPIs), warfarin, and statins
      (essential drugs covered by Part D plans) and benzodiazepines (not covered
      through Part D but potentially covered through Medicaid). RESULTS: Drug use for
      13,032 dual eligibles was evaluated. There was no significant effect of the
      transition to Medicare Part D on use of all study drugs, including the uncovered
      benzodiazepines. Cumulative reductions were seen in copayments for all covered
      drugs after implementation of Part D, ranging from 25% annually for PPIs to 53%
      for warfarin, but there was a larger increase in copayments, 91% annually, for
      benzodiazepines after the transition. The rate of switching medications was 3.0
      times as great for the PPIs after implementation of Part D than before
      implementation, but there was no significant change in the other study drug
      classes. CONCLUSION: These findings in a single, large pharmacy chain indicate
      that the transition plan for dual eligibles led to less medication
      discontinuation and switching than many had expected. The substantially greater
      cost sharing for benzodiazepines highlights the importance of implementing a
      thoughtful transition plan when executing such a national policy.

PMID- 19093931
TI  - Survival in elderly persons with Down syndrome.
AB  - The longer life expectancy now experienced by persons with Down syndrome (DS)
      makes it necessary to know the factors influencing survival in older persons with
      this syndrome. In a prospective longitudinal cohort study of dementia and
      mortality, 506 persons with DS aged 45 and older were followed for a mean of 4.5
      years (range 0.0-7.6 years). Cognitive and social functioning were tested at
      baseline and annual follow-up. The diagnosis of dementia was determined according
      to a standardized protocol. Cox proportional hazards modeling was used for
      survival analysis. Relative preservation of cognitive and functional ability is
      associated with better survival in this study population. Clinically, the most
      important disorders in persons with DS that are related to mortality are
      dementia, mobility restrictions, visual impairment, and epilepsy but not
      cardiovascular diseases. Also, level of intellectual disability and
      institutionalization are associated with mortality.

PMID- 19093932
TI  - Program at home: a Veterans Affairs Healthcare Program to deliver hospital care
      in the home.
AB  - The Portland Veterans Affairs Medical Center (PVAMC) participated in a research
      based National Demonstration and Evaluation Study of Hospital at Home Care for
      Elderly Patients. PVAMC continued hospital at home care in a modified form based
      on the results of that research phase and feedback from patients, families, and
      staff. The modified clinical program (referred to as Program @ Home) provided
      care for the same diagnoses (exacerbation of congestive heart failure,
      exacerbation of chronic obstructive pulmonary disease, community-acquired
      pneumonia, cellulitis) but differed from the research-based demonstration project
      in that it accepted patients of all ages, accepted early-discharge patients from
      the hospital, and provided a less-intensive physician and nursing model. In the
      first 42 months, 290 patients were admitted; 23% came from the emergency room,
      54% were early hospital discharge, and the remainder came from an outpatient
      clinic or home care. Average length of stay was 3.2 days, and 37% were younger
      than 65. The results describe how a home hospital program has been integrated
      into the clinical care offerings of a managed care health system and how it
      supports inpatient, primary, emergency, and home care programs.

PMID- 19093933
TI  - Setting the stage for a new strategic plan for geriatrics and extended care in
      the Veterans Health Administration: summary of the 2008 VA State of the Art
      Conference, "The changing faces of geriatrics and extended care: meeting the
      needs of veterans in the next decade".
AB  - The Department of Veterans Affairs (VA) assumed an early leadership role in
      focusing on care of elderly adults. In 1998, the Federal Advisory Committee on
      the Future of VA Long-Term Care, appointed by the VA Undersecretary for Health,
      recommended redirection of VA's extended care programs toward noninstitutional
      forms. A decade later, VA's Office of Geriatrics and Extended Care (GEC)
      initiated a strategic planning process by convening experts in geriatrics and
      health care, policy, and finance in Virginia on March 25 to 27, 2008, to present
      to VA clinicians and clinical managers the "State of the Art" of VA GEC.
      Recurring clinical themes included rising numbers and complexity of aging
      veterans, recent addition of younger veterans to VA's extended care mix,
      challenges that dementia and mental illness exert throughout GEC, and need for
      seamlessness in delivery of care across multiple venues. Ongoing research efforts
      quantifying demand and resources and validating models of care will remain
      indispensible for meeting clinical challenges. Serious undersupply of clinicians
      of all disciplines with general or specialty geriatrics knowledge persists. Much
      of VA's healthcare workforce and leadership are approaching retirement age,
      driving the need for new educational approaches, recruitment and retention
      strategies, and innovative delivery systems. Growing dependence on informal
      caregivers highlights the need for supporting these partners. VA's healthcare
      budget allocation illustrates how national policy dictates systemic, regional,
      and local clinical decisions. Rehabilitation of the newest veterans is resulting
      in systemwide efficiencies. Educating and empowering patients and families
      results in optimized utilization of health resources.

PMID- 19093934
TI  - Recruitment and retention of older adults in aging research.
AB  - Older adults continue to be underrepresented in clinical research despite their
      burgeoning population in the United States and worldwide. Physicians often
      propose treatment plans for older adults based on data from studies involving
      primarily younger, more-functional, healthier participants. Major barriers to
      recruitment of older adults in aging research relate to their substantial health
      problems, social and cultural barriers, and potentially impaired capacity to
      provide informed consent. Institutionalized older adults offer another layer of
      complexity that requires cooperation from the institutions to participate in
      research activities. This paper provides study recruitment and retention
      techniques and strategies to address concerns and overcome barriers to older
      adult participation in clinical research. Key approaches include early in-depth
      planning; minimizing exclusion criteria; securing cooperation from all interested
      parties; using advisory boards, timely screening, identification, and approach of
      eligible patients; carefully reviewing the benefit:risk ratio to be sure it is
      appropriate; and employing strategies to ensure successful retention across the
      continuum of care. Targeting specific strategies to the condition, site, and
      population of interest and anticipating potential problems and promptly employing
      predeveloped contingency plans are keys to effective recruitment and retention.

PMID- 19093935
TI  - When being thin is not a virtue.

PMID- 19093936
TI  - Challenges in clinical aging research: building the evidence base for care of the
      older adult.

PMID- 19093937
TI  - Age bias in clinical trials of Parkinson's disease treatment.

PMID- 19093939
TI  - Propensity scoring.

PMID- 19093941
TI  - Cognitive functioning appears to be a better predictor of disruptive behaviour
      than analgesic intake.

PMID- 19093942
TI  - Growth in the incidence of hospitalizations with resistant infections in elderly
      people in the United States: 2000 to 2006.

PMID- 19093943
TI  - The mental status vital sign.

PMID- 19093944
TI  - Depression and medical illness in chinese nonagenarians and centenarians.

PMID- 19093945
TI  - The positive financial contribution of home-based primary care programs:
      generating revenue or reducing health expenditure?

PMID- 19093946
TI  - Polycytemia vera presenting as sudden-onset cognitive impairment.

PMID- 19093947
TI  - Effects of ghrelin treatment on patients undergoing total hip replacement for
      osteoarthritis: different outcomes from studies in patients with cardiac and
      pulmonary cachexia.

PMID- 19093948
TI  - Rare diseases in elderly persons.

PMID- 19093949
TI  - Apolipoprotein e genotype does not predict 9-year all-cause mortality in
      brazilian older adults: the Bambui Cohort Study.

PMID- 19093950
TI  - Geriatric emergency medicine.

PMID- 19093951
TI  - Relationship between periodontal status and physical fitness in an elderly
      population of nonsmokers in Bangladesh.

PMID- 19093952
TI  - Sex differences in the prevalence of frailty in a population aged 75 and older in
      Spain.

PMID- 19093953
TI  - Delirium caused by urinary retention in elderly people: a case report and
      literature review on the "cystocerebral syndrome".

PMID- 19093954
TI  - Journal of Internal Medicine--editorial update for 2009.

PMID- 19093956
TI  - Introduction: Back to basics: mucosal immunity and novel HIV vaccine concepts.

PMID- 19093957
TI  - Human immunodeficiency virus-1 acquisition in genital mucosa: Langerhans cells as
      key-players.
AB  - Human immunodeficiency virus-1 (HIV-1) infection occurs primarily via genital
      mucosal tissues and the cellular mechanisms that affect HIV-1 acquisition are
      largely unclear. Langerhans cells (LCs) are professional antigen presenting cells
      lining the mucosal stratified squamous epithelium. It is becoming evident that
      LCs have different functions in HIV-1 transmission. HIV-1 can infect mucosal LCs,
      which subsequently efficiently transmit the virus to T cells in the lymphoid
      tissues. However, this seems to be dependent on the activation status of LCs, as
      immature LCs prevent HIV-1 infection by clearing invading HIV-1 though the C-type
      lectin langerin. Recent data demonstrate that co-infections with sexual
      transmitted infection (STIs) negate the protective function of LCs by different
      mechanisms, thereby allowing LC infection with HIV-1 and subsequently HIV-1
      transmission. Here, we will discuss the function of LCs under normal
      circumstances and in the presence of STIs or inflammation. A better understanding
      of LCs function during homeostasis and inflammation is necessary for the
      development of new strategies to prevent HIV-1 infection.

PMID- 19093959
TI  - Signalling pathways leading to IFN-alpha production in human plasmacytoid
      dendritic cell and the possible use of agonists or antagonists of TLR7 and TLR9
      in clinical indications.
AB  - Plasmacytoid dendritic cells (PDC) are highly specialized immune cells capable of
      producing large amounts of type I and III IFN in response to viral infection.
      This response is mediated through TLR7 and TLR9 signalling pathways. In addition,
      PDC can differentiate into fully mature dendritic cells able to efficiently
      crosspresent viral antigens, thus playing an important role in adaptive immunity.
      This dual property of PDC is being used in clinical settings where synthetic TLR7
      and TLR9 ligands are currently evaluated in clinical trials for the treatment of
      viral infections, allergies and cancers. Interestingly, there is evidence
      suggesting that chronic activation of PDC by endogenous RNA and DNA containing
      immune complexes maybe an important mechanism of driving autoimmunity and
      significant efforts to develop bi-functional antagonists of TLR7 and TLR9 are
      currently underway.

PMID- 19093958
TI  - NK cells in HIV-1 infection: evidence for their role in the control of HIV-1
      infection.
AB  - Increasing evidence supports the notion that the innate immune response, and in
      particular, natural killer cells play a central role in determining the quality
      of the host immune response to infection. In this review we highlight recent
      evidence that suggests that NK cells influence the clinical fate of HIV-infected
      individuals.

PMID- 19093960
TI  - Mucosal T-cell responses to HIV: responding at the front lines.
AB  - Mucosal surfaces of the body serve as the major portal of entry for human
      immunodeficiency virus (HIV). These tissues also house a majority of the body's
      lymphocytes, including the CD4(+) T cells that are the major cellular target for
      HIV infection. Mucosal surfaces are defended by innate and adaptive immune
      mechanisms, including secreted antibodies and CD8(+) cytotoxic T cells (CTL). CTL
      in mucosal lymphoid tissues may serve to limit viral replication, decreasing the
      host's viral burden as well as reducing the likelihood of sexual transmission to
      a naive host. This review summarizes recent literature on HIV-specific T-cell
      responses in mucosal tissues, with an emphasis on the gastrointestinal tract.

PMID- 19093961
TI  - Antiviral CD8+ T cells in the genital tract control viral replication and delay
      progression to AIDS after vaginal SIV challenge in rhesus macaques immunized with
      virulence attenuated SHIV 89.6.
AB  - The recently failed clinical efficacy trial of an acquired immunodeficiency
      syndrome (AIDS) vaccine that elicits antiviral CD8(+) T-cell responses has
      emphasized the challenge of producing an effective vaccine against human
      immunodeficiency virus (HIV). In the simian immunodeficiency virus (SIV)/ rhesus
      monkey model of AIDS, live-attenuated lentivirus 'vaccines' provide the best
      protection from uncontrolled viral replication and clinical disease after
      pathogenic SIV challenge. This review summarizes a recent series of studies in
      which we show that after vaginal SIV challenge of rhesus macaques immunized with
      an attenuated lentivirus protection from uncontrolled viral replication is
      primarily mediated by CD8(+) T cells in the vaginal mucosa. Immunization with a
      chimeric simian/human immunodeficiency virus (SHIV) results in a systemic
      infection that induces a moderate population of SIV-specific CD8(+) and CD4(+) T
      cells with cytolytic potential in the vaginal mucosa. Depletion of CD8(+) T cells
      at the time of SIV challenge completely abrogates the protection mediated by
      prior infection with attenuated SHIV. Further after vaginal SIV challenge, the
      only significant expansion of SIV-specific T cells occurs in the vagina in these
      animals. No significant expansion of T-cell responses was observed in systemic
      lymphoid tissues. Thus, the presence of SIV-specific CD8(+) T cells in the vagina
      on the day of vaginal SIV challenge and a modest expansion of local effector T
      cells is sufficient to stop uncontrolled SIV replication. It seems that T-cell
      based vaccine strategies that can elicit mucosal effector CD8(+) T-cell
      populations and avoid inducing systemic T-cell proliferation upon exposure to HIV
      have the greatest potential for mimicking the success of live-attenuated
      lentiviral vaccines.

PMID- 19093963
TI  - Immunity in natural SIV infections.
AB  - In stark contrast to human immunodeficiency virus (HIV)-infected individuals who,
      if left untreated, almost invariably progress to acquired immunodeficiency
      syndrome (AIDS), natural hosts for the simian immunodeficiency viruses (SIV)
      remain asymptomatic throughout the course of infection. This observation
      represents one of the main unresolved puzzles of AIDS research, particularly if
      one considers that natural SIV infections are characterized by chronically high
      levels of viraemia as well as intrinsic virus cytopathicity comparable with that
      of HIV. In this review, I discuss the basic immunological features of natural,
      nonpathogenic SIV infections, the evidence suggesting that attenuated, rather
      than extraordinarily strong, immune responses to the virus may favour their
      benign course, and the implications of these findings in terms of HIV therapy and
      vaccines.

PMID- 19093964
TI  - Genetic correlates of protection against HIV infection: the ally within.
AB  - Repeated exposure to HIV does not necessarily result in infection and HIV
      infection does not inevitably lead to the development of the AIDS. Multiple
      immunological and genetic features can confer resistance to HIV acquisition and
      progression at different steps in viral infection; a full understanding of these
      mechanisms could result in the development of novel therapeutic and vaccine
      approaches for HIV infection. In this review, we focus on the genetic mechanisms
      associated with resistance to HIV infection and to the progression to AIDS.

PMID- 19093962
TI  - Immune dysregulation in human immunodeficiency virus infection: know it, fix it,
      prevent it?
AB  - Infection of humans by the human immunodeficiency virus (HIV) causes a
      progressive, multifactorial impairment of the immune system eventually leading to
      the acquired immunodeficiency syndrome (AIDS). No cure or vaccine exists yet
      against HIV infection. More worrisome is the fact that despite having identified
      HIV as the cause of the AIDS, we still do not understand what pathogenic
      mechanisms lead to the debacle of the immune system. In this review we consider
      the extent and the limits of our knowledge of HIV pathogenesis, and how this
      knowledge may be used to design preventive and therapeutic approaches.

PMID- 19093965
TI  - Developing an HIV cytotoxic T-lymphocyte vaccine: issues of CD8 T-cell quantity,
      quality and location.
AB  - Issues of quantity, quality and location impact the ability of CD8 T cells to
      mediate protection from infection. These issues are considered in light of human
      immunodeficiency virus (HIV)/simian immunodeficiency virus (SIV) vaccination.
      Methods are reviewed that result in 100- to 1000-fold higher frequencies of
      vaccine-specific memory CD8 T cells than that achieved by current HIV/SIV vaccine
      approaches. Data demonstrating that location within mucosal tissues has a direct
      impact on memory CD8 T-cell function are discussed. Arguments are made that
      establishing memory CD8 T cells within mucosal sites of transmission, a priori to
      natural infection, may be essential for conferring optimal and rapid protection.
      Lastly, it is proposed that heterologous prime-boost vaccination with recombinant
      live replicating vectors, which has the potential to induce tremendous numbers of
      cytolytic memory CD8 T cells within mucosal tissues, would provide a far more
      stringent test of the hypothesis that memory CD8 T cells could, in principal,
      form the basis for a preventative HIV vaccine.

PMID- 19093967
TI  - Immunological tests to diagnose active tuberculosis.

PMID- 19093968
TI  - Location of caspase 3-like protease in the development of sieve element and
      tracheary element of stem in Cucurbita moschata.
AB  - The casepase is considered to regulate the process of programmed cell death in
      the development of organisms. In this study, caspase 3-like protease was detected
      by immunohistochemistry and immunoelectron microscopy during the development of
      sieve element and tracheary element of stem in Cucurbita moschata Duch. Antibody
      with brown color (under light microscopy) and gold particles (under transmission
      electron microscopy) for detecting caspase 3-like protease was mainly displayed
      in inner phloem, external phloem and xylem in the region close to procambium.
      From the results it was considered that caspase 3-like protease did exist in
      vascular elements and played different roles during the development of sieve and
      tracheary elements, and different types of programmed cell death might be carried
      out. The caspase 3-like protease mainly participated in making cytoplasmic
      streaming cease and in degrading P-protein bodies; however, it rarely
      participated in the function for signal transferring in the developmental sieve
      element. However, it might induce calcium accumulation for rupturing the
      tonoplast in the signal of PCD in the developmental tracheary element.

PMID- 19093969
TI  - Anatomical and chemical alterations but not photosynthetic dynamics and
      apoplastic transport changes are involved in the brittleness culm mutation of
      rice.
AB  - Brittleness culm is an important agronomic trait that has a potential usefulness
      in agricultural activity as animal forage although the developmental mechanism is
      not clear yet. In the present study, the anatomical and chemical characteristics
      as well as some ecophysiological features in the brittleness culm mutation of
      rice (Oryza sativa L.) were investigated. Compared with the wild type (WT), the
      brittleness culm mutant (bcm) exhibited higher culm vascular bundle distance and
      lower culm wall thickness, leaf interveinal distance and leaf thickness. Ratio of
      bundle sheath cell/whole bundle and areas of whole vascular bundles and bundle
      sheath of leaves were reduced while ratios of xylem and phloem to whole bundles
      were elevated in bcm. The Fourier transform infrared (FTIR) microspectroscopy
      analysis and further histochemical and physiological measurements revealed that
      the different contents and depositions of cell wall components such as pectins,
      lignin, suberin and cellulose all participated in the mutation of brittleness.
      However, the mutant presented no significant changes in leaf photosynthetic
      dynamics and apoplastic transport ability. These results strongly indicate that
      the alterations in anatomical and chemical characteristics, rather than changes
      in major ecophysiological features such as photosynthesis and apoplastic
      transport were involved in the brittleness mutation of rice.

PMID- 19093971
TI  - AtMGT7: An Arabidopsis gene encoding a low-affinity magnesium transporter.
AB  - Magnesium (Mg(2+)) is one of the essential cations in all cells. Although the
      Mg(2+) transport mechanism has been well-documented in bacteria, less is known
      about Mg(2+) transporters in eukaryotes. The AtMGT gene family encoding putative
      magnesium transport proteins had been described previously. We report here that
      one of the Arabidopsis MGT family members, the AtMGT7 gene, encodes two mRNAs
      that have resulted from alternative splicing variants, designated AtMGT7a and
      AtMGT7b. Interestingly, the two mRNA variants were expressed with different
      patterns with AtMGT7a expressing in all organs, but AtMGT7b appearing only in
      root and flowers. The AtMGT7a variant functionally complemented a bacterial
      mutant lacking Mg(2+) transport capacity, whereas AtMGT7b did not. The (63)Ni(2+)
      tracer uptake analysis in the bacterial model showed that AtMGT7a mediated low
      affinity transport of Mg(2+). Consistent with the complementation assay result,
      (63)Ni(2+) tracer uptake analysis revealed that AtMGT7b did not transport Mg(2+).
      This study therefore has identified from a higher plant the first low-affinity
      Mg(2+) transporter encoded by a gene with alternatively spliced transcripts that
      produce proteins with distinct functions.

PMID- 19093970
TI  - Hydrogen sulfide promotes wheat seed germination and alleviates oxidative damage
      against copper stress.
AB  - With the enhancement of copper (Cu) stress, the germination percentage of wheat
      seeds decreased gradually. Pretreatment with sodium hydrosulfide (NaHS), hydrogen
      sulfide (H(2)S) donor alleviated the inhibitory effect of Cu stress in a dose
      dependent manner; whereas little visible symptom was observed in germinating
      seeds and radicle tips cultured in NaHS solutions. It was verified that H(2)S or
      HS(-) rather than other sulfur-containing components derived from NaHS attribute
      to the potential role in promoting seed germination against Cu stress. Further
      studies showed that NaHS could promote amylase and esterase activities, reduce Cu
      induced disturbance of plasma membrane integrity in the radicle tips, and sustain
      lower levels of malondialdehyde and H(2)O(2) in germinating seeds. Furthermore,
      NaHS pretreatment increased activities of superoxide dismutase and catalase and
      decreased that of lipoxygenase, but showed no significant effect on ascorbate
      peroxidase. Alternatively, NaHS prevented uptake of Cu and promoted the
      accumulation of free amino acids in seeds exposed to Cu. In addition, a rapid
      accumulation of endogenous H(2)S in seeds was observed at the early stage of
      germination, and higher level of H(2)S in NaHS-pretreated seeds. These data
      indicated that H(2)S was involved in the mechanism of germinating seeds'
      responses to Cu stress.

PMID- 19093972
TI  - Carbon monoxide-induced stomatal closure involves generation of hydrogen peroxide
      in Vicia faba guard cells.
AB  - Here the regulatory role of CO during stomatal movement in Vicia faba L. was
      surveyed. Results indicated that, like hydrogen peroxide (H(2)O(2)), CO donor
      Hematin induced stomatal closure in dose- and time-dependent manners. These
      responses were also proven by the addition of gaseous CO aqueous solution with
      different concentrations, showing the first time that CO and H(2)O(2) exhibit the
      similar regulation role in the stomatal movement. Moreover, our data showed that
      ascorbic acid (ASA, an important reducing substrate for H(2)O(2) removal) and
      diphenylene iodonium (DPI, an inhibitor of the H(2)O(2)-generating enzyme NADPH
      oxidase) not only reversed stomatal closure by CO, but also suppressed the
      H(2)O(2) fluorescence induced by CO, implying that CO induced-stomatal closure
      probably involves H(2)O(2) signal. Additionally, the CO/NO scavenger hemoglobin
      (Hb) and CO specific synthetic inhibitor ZnPPIX, ASA and DPI reversed the
      darkness-induced stomatal closure and H(2)O(2) fluorescence. These results show
      that, perhaps like H(2)O(2), the levels of CO in guard cells of V. faba are
      higher in the dark than in light, HO-1 and NADPH oxidase are the enzyme systems
      responsible for generating endogenous CO and H(2)O(2) in darkness respectively,
      and that CO is involved in darkness-induced H(2)O(2) synthesis in V. faba guard
      cells.

PMID- 19093966
TI  - Dendritic cell-based human immunodeficiency virus vaccine.
AB  - Dendritic cells (DC) have profound abilities to induce and coordinate T-cell
      immunity. This makes them ideal biological agents for use in immunotherapeutic
      strategies to augment T-cell immunity to HIV infection. Current clinical trials
      are administering DC-HIV antigen preparations carried out ex vivo as proof of
      principle that DC immunotherapy is safe and efficacious in HIV-infected patients.
      These trials are largely dependent on preclinical studies that will provide
      knowledge and guidance about the types of DC, form of HIV antigen, method of DC
      maturation, route of DC administration, measures of anti-HIV immune function and
      ultimately control of HIV replication. Additionally, promising immunotherapy
      approaches are being developed based on targeting of DC with HIV antigens in
      vivo. The objective is to define a safe and effective strategy for enhancing
      control of HIV infection in patients undergoing antiretroviral therapy.

PMID- 19093973
TI  - Possible involvement of reactive oxygen species scavenging enzymes in desiccation
      sensitivity of Antiaris toxicaria seeds and axes.
AB  - The relationships among desiccation sensitivities of Antiaris toxicaria seeds and
      axes, changes in activities of superoxide dismutase (SOD), ascorbate peroxidase
      (APX), catalase (CAT), glutathione reductase (GR) and dehydroascorbate reductase,
      (DHAR), production rate of superoxide radical (.O(2) (-)), and the contents of
      hydrogen peroxide (H(2)O(2)) and thiobarbituric acid (TBA)-reactive substance
      were studied. Desiccation tolerance of seeds and axes decreased with dehydration.
      Desiccation tolerance of axes was higher than that of seeds, and that of
      epicotyls was higher than radicles. Activities of SOD, CAT and DHAR of seeds
      increased during the initial phase of dehydration, and then decreased with
      further dehydration, whereas activities of APX and GR decreased with dehydration.
      These five enzyme activities of axes, however, increased during the initial phase
      of dehydration, and then decreased with further dehydration. The rate of
      superoxide radical production, and the contents of H(2)O(2) and TBA-reactive
      products of seeds and axes gradually increased with dehydration. These results
      show that the A. toxicaria seed is a typical recalcitrant seed. Loss of
      desiccation tolerance in seeds and axes was correlated with the increase in .O(2)
      (-) production rate, content of H(2)O(2) and TBA-reactive products, and the
      decline of antioxidant enzyme activities of seeds and axes.

PMID- 19093974
TI  - Iron deficiency-induced increase of root branching contributes to the enhanced
      root ferric chelate reductase activity.
AB  - In various plant species, Fe deficiency increases lateral root branching.
      However, whether this morphological alteration contributes to the Fe deficiency
      induced physiological responses still remains to be demonstrated. In the present
      research, we demonstrated that the lateral root development of red clover
      (Trifolium pretense L.) was significantly enhanced by Fe deficient treatment, and
      the total lateral root number correlated well with the Fe deficiency-induced
      ferric chelate reductase (FCR) activity. By analyzing the results from Dasgan et
      al. (2002), we also found that although the two tomato genotypes line227/1 (P1)
      and Roza (P2) and their reciprocal F1 hybrid lines ("P1 x P2" and "P2 x P1") were
      cultured under two different lower Fe conditions (10(-6) and 10(-7) M FeEDDHA),
      their FCR activities are significantly correlated with the lateral root number.
      More interestingly, the -Fe chlorosis tolerant ability of these four tomato lines
      displays similar trends with the lateral root density. Taking these results
      together, it was proposed that the Fe deficiency-induced increases of the lateral
      root should play an important role in resistance to Fe deficiency, which may act
      as harnesses of a useful trait for the selection and breeding of more Fe
      efficient crops among the genotypes that have evolved a Fe deficiency-induced Fe
      uptake system.

PMID- 19093975
TI  - Simple traits among diaspore weight/number, plant height and ability of
      vegetative propagation.
AB  - Several expected correlations among followed internal plant traits were confirmed
      using the dataset of 492 herbaceous species from the temporal zone of Central
      Europe. Average diaspore weight (seed mass), reproductive capacity of population
      (number of produced diaspores), species height, and ability of lateral spread
      were the plant traits considered. The evident correlations were confirmed among
      all investigated traits: (i) The reproductive capacity of population negatively
      correlated with diaspore weight, plant height, and vegetative propagation. The
      diaspore weight and their number are closely correlated and co-adapted. (ii)
      Bigger plant species produce bigger diaspores. These trends are obvious at the
      inter- and intra-family levels. (iii) Larger plant species showed higher ability
      to vegetative propagation.

PMID- 19093976
TI  - Intensity and importance of competition for a grass (Festuca rubra) and a legume
      (Trifolium pratense) vary with environmental changes.
AB  - How plant competition varies across environmental gradients has been a long
      debate among ecologists. We conducted a growth chamber experiment to determine
      the intensity and importance of competition for plants grown in changed
      environmental conditions. Festuca rubra and Trifolium pratense were grown in
      monoculture and in two- and/or three-species mixtures under three environmental
      treatments. The measured competitive variations in terms of growth (height and
      biomass) were species-dependent. Competition intensity for Festuca increased with
      decreased productivity, whilst competition importance displayed a humpback
      response. However, significant response was detected in neither competition
      intensity nor importance for Trifolium. Intensity and importance of competition
      followed different response patterns, suggesting that they may not be correlated
      along an environmental gradient. The biological and physiological variables of
      plants play an important role to determine the interspecific competition
      associated with competition intensity and importance. However, the competitive
      feature can be modified by multiple environmental changes which may increase or
      hinder how competitive a plant is.

PMID- 19093977
TI  - Assessing the response of seasonal variation of net primary productivity to
      climate using remote sensing data and geographic information system techniques in
      Xinjiang.
AB  - Net primary productivity (NPP) is a key component of energy and matter
      transformation in the terrestrial ecosystem, and the responses of NPP to global
      change locally and regionally have been one of the most important aspects in
      climate-vegetation relationship studies. In order to isolate causal climatic
      factors, it is very important to assess the response of seasonal variation of NPP
      to climate. In this paper, NPP in Xinjiang was estimated by NOAA/AVHRR Normalized
      Difference Vegetation Index (NDVI) data and geographic information system (GIS)
      techniques. The impact of climatic factors (air temperature, precipitation and
      sunshine percentage) on seasonal variations of NPP was studied by time lag and
      serial correlation ageing analysis. The results showed that the NPP for different
      land cover types have a similar correlation with any one of the three climatic
      factors, and precipitation is the major climatic factor influencing the seasonal
      variation of NPP in Xinjiang. It was found that the positive correlation at 0 lag
      appeared between NPP and precipitation and the serial correlation ageing was 0 d
      in most areas of Xinjiang, which indicated that the response of NPP to
      precipitation was immediate. However, NPP of different land cover types showed
      significant positive correlation at 2 month lag with air temperature, and the
      impact of which could persist 1 month as a whole. No correlation was found
      between NPP and sunshine percentage.

PMID- 19093978
TI  - Effects of irrigation and nitrogen on the performance of aerobic rice in northern
      China.
AB  - Aerobic rice is a new production system in which specially-developed varieties
      are grown under non-flooded, non-puddled, and non-saturated soil conditions. In
      2003-2004, irrigation x Nitrogen experiments were carried out near Beijing using
      variety HD297. Water treatments included four irrigation levels, and Nitrogen
      treatments included different fertilizer N application rates and different
      numbers of N splits. The highest yields were 4 460 kg/ha with 688 mm of total
      (rain plus irrigation) water input in 2003 and 6 026 kg/ha with 705 mm of water
      input in 2004. Because of the quite even distribution of rainfall in both years,
      the four irrigation treatments did not result in large differences of soil water
      conditions. There were few significant effects of irrigation on biomass
      accumulation, but yield increased with the total amount of water applied. High
      yields coincided with high harvest index and high percentages of grain filling.
      The application of fertilizer N either reduced biomass and yield or kept it at
      the same level as 0 N and consistently reduced the percentage grain filling and 1
      000-grain weight. With the highest water application, five splits of N gave
      higher yield than three splits, whereas three splits gave higher yield than five
      splits with lower water applications.

PMID- 19093981
TI  - Working memory functioning in children with learning disabilities: does
      intelligence make a difference?
AB  - BACKGROUND: Children with learning disabilities are identified by their severe
      learning problems and their deficient school achievement. On the other hand,
      children with sub-average school achievement and sub-average intellectual
      development are thought to suffer from a general intellectual delay rather than
      from specific learning disabilities. The open question is whether these two
      groups are characterised by differences in their cognitive functioning. The
      present study explored several functions of working memory. METHOD: A working
      memory battery with tasks for the phonological loop, the visual-spatial sketchpad
      and central executive skills was presented in individual sessions to 27 children
      with learning disabilities and normal IQ (ICD-10: mixed disorders of scholastic
      skills), 27 children with learning disabilities and low IQ (intellectual
      disabilities), and a control group of 27 typically developing children with
      regular school achievement levels and normal IQ. RESULTS: The results reveal an
      overall deficit in working memory of the two groups with learning disabilities
      compared with the control group. However, unexpectedly, there were no differences
      between the two groups of children with disabilities (normal vs. low IQ).
      CONCLUSIONS: These findings do not support the notion of different cognitive
      functioning because of differences in intelligence of these two groups. In the
      ongoing discussion about the role of intelligence (especially as to the
      postulated discrepancy between intelligence and school achievement in diagnosis
      and special education), our findings might lead to rethinking the current
      practice of treating these two groups as fundamentally different.

PMID- 19093982
TI  - Impact of environmental factors on community participation of persons with an
      intellectual disability: a systematic review.
AB  - STUDY DESIGN: A systematic review of the literature. OBJECTIVES: To describe
      which environmental factors have an impact on community participation of persons
      with an intellectual disability. METHODS: A systematic literature search was
      conducted for the period of 1996-2006 in Pubmed, CINAHL and PSYCINFO. Search
      terms were derived from the International Classification of Functioning,
      Disability and Health. Three investigators assessed the relevance of the studies
      identified using predefined selection criteria. Aspects of community
      participation included were: domestic life; interpersonal interactions and
      relationships; major life areas; community, civic and social life. Environmental
      factors included were: products and technology; natural environment and human
      made changes to environment; support and relationships; attitudes; services,
      systems and policies. RESULTS: Out of 236 initial hits, 9 quantitative studies
      and 2 qualitative studies met the predefined selection criteria and were included
      in the study. Various research instruments were used in the studies and only one
      study used a conceptual framework. The review allowed the identification of a
      number of environmental factors positively affecting participation: opportunities
      to make choices; variety and stimulation of the environment of facilities;
      opportunities for resident involvement in policy making; small residential
      facilities; opportunities for autonomy; vocational services; social support;
      family involvement; assistive technology; and positive staff attitudes. A number
      of identified environmental factors negatively affecting participation are: lack
      of transport and not feeling accepted. DISCUSSION: It can be concluded that
      little has been published about the impact of environmental factors on community
      participation. Many studies do not clearly define the concept of community
      participation. Research on the impact of environmental factors on community
      participation so far seems not to be based on a theoretical framework. Most
      studies focused on the impact of services on community participation in general.

PMID- 19093983
TI  - Ideas and thoughts of Italian teachers on the professional future of persons with
      disability.
AB  - BACKGROUND: The literature places special focus on the quality of life (QoL) of
      individuals with disability and on their self-determination and social and work
      participation. The field of vocational guidance also considers the satisfaction
      these individuals experience concerning their future crucial to their QoL. At the
      same time, however, persons with disability are at great risk of not making
      highly advantageous choices for their future. Hence, teachers and career
      counsellors can play an important role in vocational guidance for persons with
      disability. METHODS: The present study was aimed at investigating the ideas of a
      group of teachers asked to describe in writing the future of hypothetical
      students with disability. Their descriptions were first analysed to verify
      whether any reference was made to the construct of QoL and whether a significant
      role was attributed to aspects of work inclusion and work satisfaction. Response
      category differences were then compared for curricular teachers vs. specialised
      teachers, elementary school teachers vs. middle school teachers, and low self
      efficacy vs. high self-efficacy teachers. RESULTS: Teachers describing the future
      of a hypothetical student with Down's syndrome mentioned some aspects of QoL and
      emphasised certain features over others. Several category type differences
      teachers emerged, although not always in line with expectations. CONCLUSIONS:
      Teachers' ideas on the future of individuals with intellectual disability are
      characterised by a certain bias towards the restrictions that impairment can
      imply. In consideration of our findings, the need for training actions is
      highlighted.

PMID- 19093984
TI  - Foreword: On the cusp: insight and perspectives on health reform.

PMID- 19093986
TI  - Aiming high for the U.S. health system: a context for health reform.
AB  - Policy officials often assert that the U.S. has the best health care system in
      the world, but a recent scorecard on U.S. health system performance finds that
      the U.S. achieves a score of only 65 out of a possible 100 points on key
      indicators of performance in five key domains: healthy lives, access, quality,
      equity, and efficiency, where 100 represents the best achieved performance in
      other countries or within the U.S. The U.S. should aim higher by adopting a set
      of policies that will extend affordable health insurance to all; align financial
      incentives for health care providers to enhance value and achieve savings;
      organize the health care system around the patient to ensure that care is
      accessible and coordinated; meet and raise benchmarks for high-quality, efficient
      care; and ensure accountable national leadership and public-private
      collaboration. The incoming president and Congress should aspire to have the best
      health system in the world--not just assert it--and can do so by learning from
      examples of excellence within the U.S. and abroad.

PMID- 19093985
TI  - America's uninsured: the statistics and back story.
AB  - This article provides an overview of why health insurance matters, a profile of
      the uninsured, and a discussion of the roles and limits of private and public
      health insurance as sources of coverage. It concludes with reflections on the
      current health insurance environment and prospects for reform.

PMID- 19093987
TI  - Private gain and public pain: financing American health care.
AB  - Health care spending comprises about 16% of the total United States gross
      domestic product and continues to rise. This article examines patterns of health
      care spending and the factors underlying their proportional growth. We examine
      the "usual suspects" most frequently cited as drivers of health care costs and
      explain why these may not be as important as they seem. We suggest that the drive
      for technological advancement, coupled with the entrepreneurial nature of the
      health care industry, has produced inherently inequitable and unsustainable
      health care expenditure and growth patterns. Successful health reform will need
      to address these factors and their consequences.

PMID- 19093988
TI  - Protect the sick: health insurance reform in one easy lesson.
AB  - In thinking about how to expand insurance coverage, the issue that matters is
      whether insurance enables sick and high-risk people to get medical care. Over the
      course of three decades, market-oriented insurance reforms have shifted more
      costs of illness onto people who need and use medical care. By making the users
      of care pay for it (or even some of it), cost-sharing discourages sick people
      from getting care, even if they have insurance, and for people with low-incomes
      and tight budgets, cost-sharing can effectively deny them access to care. Thus,
      covering or not covering sick people is the core issue of health insurance
      reform, both as a determinant of support and opposition to proposals, and as the
      proper yardstick for evaluating reform ideas.

PMID- 19093989
TI  - There's "private" and then there's "private": ERISA, its impact, and options for
      reform.
AB  - The Employee Retirement Income Security Act of 1974 (ERISA), a federal law
      regulating private employer-sponsored employee benefit plans, was primarily
      designed for pension plans, but has had a profound impact on state health care
      reform efforts. ERISA's broad preemption language has been judicially interpreted
      to preclude states from most forms of regulation of employer health plans,
      including benefit design (except through regulation of insurance products) and
      incorporating employer expenditure requirements in state health reform financing.
      But since 1974, Congress has never seriously returned to reexamine several
      fundamental questions: Should employers be required to offer or contribute to
      employee health coverage? Should ERISA preempt state efforts to take such
      actions? Or should ERISA incorporate more comprehensive regulation of health
      plans in these areas? Although the politics of ERISA preemption have thus far
      blocked federal reform, while allowing state reform activity to be simultaneously
      curtailed, new health reform efforts may force Congress to address these
      questions.

PMID- 19093990
TI  - Why public programs matter--and will continue to matter--even after health
      reform.
AB  - Regardless of how health reform proceeds, we will continue to need public
      insurance programs to care for the poor, cover health problems not addressed by
      private insurance, and support the nation's health care infrastructure. This
      article examines that continuing role.

PMID- 19093991
TI  - War, its aftermath, and U.S. health policy: toward a comprehensive health program
      for America's military personnel, veterans, and their families.
AB  - This essay discusses the challenges faced by veterans returning to society in
      light of the current organization and structure of the military, veterans', and
      overall U.S. health care systems. It also addresses the need for an integrated
      health care financing and delivery system to ensure a continuum of care for
      service members, veterans, dependents, and other family members. The health care
      systems of both the Department of Defense and the Department of Veterans Affairs
      execute their responsibilities to active duty service members, while their
      families and retirees/veterans are under separate legal authorities. Although
      they perform their mandates with extraordinary commitment and demonstrably high
      quality, both systems need to explore improved communication, coordination, and
      sharing, as well as increased collaboration with the Department of Health and
      Human Services programs serving the same populations, far beyond current efforts.
      The health care-related missions and the locus of health care delivery of each
      agency are admittedly unique, but their distinctions must not be permitted to
      impede system integration and coordination of a continuum of care provided to the
      men and women who serve the nation, and their families.

PMID- 19093992
TI  - The states' role in national health reform.
AB  - The respective roles of states and the federal government in health reform is a
      defining feature of any proposal. Heterogeneity among states implies the need for
      different approaches in different places, but a possible consequence is variation
      in results and outcomes around the nation.

PMID- 19093993
TI  - Reducing racial, ethnic, and socioeconomic disparities in health care:
      opportunities in national health reform.
AB  - Policy often focuses on reducing health care disparities through interventions at
      the patient and provider level. While unquestionably important, system-wide
      reforms to reduce uninsurance, improve geographic availability of services,
      increase workforce diversity, and promote clinical best practices are essential
      for progress in reducing disparities.

PMID- 19093994
TI  - Aging, primary care, and self-sufficiency: health care workforce challenges
      ahead.
AB  - A combination of "environmental factors" in the U.S. has led to an increased
      demand for health care professionals. However, there has been a significant
      decrease in the number of U.S. medical graduates selecting careers in family
      medicine and general internal medicine, thus driving demand for international
      medical graduates. At the heart of our national workforce policy needs to be good
      domestic and foreign policies, such as self-sufficiency approaches that include
      strategies to incentivize rural and underserved practice for U.S. medical
      graduates.

PMID- 19093995
TI  - Building an information technology infrastructure.
AB  - The widespread adoption of health information technology (HIT) has been
      recognized as both a necessary element of health reform and a required building
      block of a modern, high performing health care system.

PMID- 19093996
TI  - Should a reformed system be prepared for public health emergencies, and what does
      that mean anyway?
AB  - Any reformed health care system must be able to react to and mitigate the
      consequences of a public health emergency. This article identifies four essential
      components of public health emergency preparedness, and presents measures that
      can be taken immediately to improve our capacity to respond to emergencies.

PMID- 19093997
TI  - Nine lessons for health reform: or will we finally learn from the past?
AB  - Health care reform sits, once again, in the eye of the political storm. This
      article, based on an analysis of past health care debates, offers nine historical
      lessons for contemporary reformers. We describe the most important political do's
      and don'ts.

PMID- 19093998
TI  - Health care reform: lessons from the past, lessons for the future.
AB  - Health care reform is a perennial issue in elections--partly because of the
      challenges facing health care and especially because health care is an important
      issue for the swing voters. Making reform happen is harder. There are deep
      divisions within each of the parties--not apparent during elections. Bipartisan
      support--and the willingness to accept the best legislation that can be passed as
      "good enough"--will be key.

PMID- 19093999
TI  - Proving the skeptics wrong: why major health reform can happen despite the odds.
AB  - Notwithstanding the pessimistic prognostications of Washington's cynical elite,
      broad health reform is achievable precisely because it is an economic and fiscal
      imperative. Indeed, the stakeholders with the greatest power to promote or
      undermine progress are on board, concluding that the status quo is unsustainable
      and the second best option is no longer to do nothing.

PMID- 19094000
TI  - Introduction: Organ donation and death from unexpected circulatory arrest:
      engaging the recommendations of the Institute of Medicine.

PMID- 19094001
TI  - The Washington, D.C. experience with uncontrolled donation after circulatory
      determination of death: promises and pitfalls.
AB  - The author recounts his experience with an uDCD program that ran for three years
      at the Washington Hospital I Center in Washington, D.C. in the 1990s. Challenges,
      I benefits, and lessons learned are considered in depth. A I primary focus is the
      importance of community education, Organ Procurement Organization support, and
      the need for immediate in-situ preservation of organs.

PMID- 19094002
TI  - Legal authority to preserve organs in cases of uncontrolled cardiac death:
      preserving family choice.
AB  - The gap between the number of organs available for transplant and the number of
      individuals who need transplanted organs continues to increase. At the same time,
      thousands of transplantable organs are needlessly overlooked every year for the
      single reason that they come from individuals who were declared dead according to
      cardio pulmonary criteria. Expanding the donor population to individuals who die
      uncontrolled cardiac deaths will reduce this disparity, but only if organ
      preservation efforts are utilized. Concern about potential legal liability for
      temporary preservation of organs pending a search for family members appears to
      be one of the impediments to wider use of donation in cases of uncontrolled
      cardiac death in states without statutes explicitly authorizing such action.
      However, we think that the risk of liability for organ preservation under these
      circumstances is de minimis, and that concerns about legal impediments to
      preservation should yield to the ethical imperative of undertaking it.

PMID- 19094003
TI  - Donation after uncontrolled cardiac death (uDCD): a review of the debate from a
      European perspective.
AB  - Presumed consent alone will not solve the organ shortage, but it will create an
      ethical and legal context that supports organ donation, respects individuals who
      object to organ donation, relieves families from the burden of decision making,
      and can save lives.

PMID- 19094004
TI  - (Uncontrolled) donation after cardiac determination of death: a note of caution.
AB  - In this short article, we articulate a position that organ recovery from
      uncontrolled DCD (uDCD)--primarily patients who have suffered a cardiac arrest-
      is unlikely to result in a significant number of organs, and this small gain must
      be balanced against significant risk of unduly influencing resuscitation provider
      decision-making, and jeopardizing public trust in the propriety of organ donation
      and transplantation.

PMID- 19094005
TI  - Organ donation after circulatory determination of death: lessons and unresolved
      controversies.
AB  - This article responds to the four pieces in this special symposium of the Journal
      of Law, Medicine & Ethics on uncontrolled organ donation following circulatory
      death (uDCD). The response will focus on lessons and debates about the kinds of
      consent necessary and sufficient for temporary organ preservation in the context
      of DCD and for organ donation itself; on conflicts of obligation, loyalty, and
      interest in DCD and ways to address those conflicts; and on benefit, cost, risk
      assessments of uDCD programs, including measures to achieve a more favorable
      balance of benefits, costs, and risks.

PMID- 19094006
TI  - Preemption and the obesity epidemic: state and local menu labeling laws and the
      nutrition labeling and education act.
AB  - Obesity is widely recognized as a preventable cause of death and disease.
      Reducing obesity among adults and children has become a national health goal in
      the United States. As one approach to the obesity epidemic, public health
      practitioners and others have asserted the need to provide consumers with
      information about the foods they eat. Some state and local governments across the
      United States have introduced menu labeling bills and regulations that require
      restaurants to post information, such as calorie content, for foods offered on
      their menus or menu boards. A major dilemma is whether state and local menu
      labeling laws are preempted by the federal Nutrition Labeling and Education Act
      (NLEA). While few courts have addressed this issue, ongoing litigation in New
      York City provides an early glimpse of judicial interpretation in this area. This
      article explores these preemption issues, arguing that appropriately written and
      implemented menu labeling laws should not be preempted by the NLEA. We offer
      guidance for states and localities that wish to develop and implement menu
      labeling laws.

PMID- 19094007
TI  - The corporate transformation of medical specialty care: the exemplary case of
      neonatology.
AB  - The key to wealth in health care is the physician, who certifies to third-party
      payers that health care items and services are necessary for patient care. To
      compete more effectively for this wealth, physician specialists are organizing
      their practices into for-profit corporations and employing other physicians.
      Focusing on neonatology, this article describes the prevailing business model of
      these for-profit medical groups as controlling employed physicians through
      restrictive employment contract provisions, e.g., non-compete and mandatory
      arbitration clauses. With this business model and because of deficiencies in
      current law, for-profit medical groups eliminate competition from other physician
      specialists to the detriment of patients and consumers.

PMID- 19094008
TI  - Neonatal pain relief and the Helsinki Declaration.
AB  - The Helsinki Declaration is the universally accepted standard for ethical
      behavior in research involving human subjects. The Declaration calls for research
      studies to compare new therapies to the best current therapies. Despite this
      standard, multiple studies of pain relief interventions in newborns have
      recruited placebo controls instead of active controls using the best current
      therapy. These studies are evaluated using the standards required by the Helsinki
      Declaration, and the reasons for the ethical shortcomings of these studies are
      explored.

PMID- 19094009
TI  - Brain death revisited: the case for a national standard.
AB  - The concept of brain death--first defined decades ago--still presents medical,
      ethical, and legal challenges despite its widespread acceptance in clinical
      practice and in law. This article reviews the medicine, law, and ethics of brain
      death, including the current inconsistencies in brain death determinations, which
      a lack of standardized federal policy promotes, and argues that a standard brain
      death policy to be used by all hospitals in all states should be created.

PMID- 19094010
TI  - Currents in contemporary ethics. GINA, the ADA, and genetic discrimination in
      employment.

PMID- 19094011
TI  - Teaching health law. What we in law can learn from our colleagues in medicine
      about teaching students how to practice their chosen profession.

PMID- 19094013
TI  - Recent developments in health law. The Genetic Information Nondiscrimination Act
      of 2008: "First major Civil Rights bill of the century" bars misuse of genetic
      test results.

PMID- 19094014
TI  - Abstracts from the Annual Congress of the British Society for Immunology.
      November 17-21, 2008. Glasgow, United Kingdom.

PMID- 19094015
TI  - Comparison between light and electron microscopy in canine and feline renal
      pathology: a preliminary study.
AB  - The aim of this study is to compare the accuracy and clinical use of light and
      transmission electron microscopy in detecting the early stages of renal
      pathologies in domestic animals. We examined 30 samples of renal tissue from cats
      and dogs referred to the Veterinary Hospital of the Department of Animal
      Pathology for different systemic diseases. The progressions of the kidney
      pathologies were classified using the scheme system proposed by the International
      Renal Interest Society. All samples were submitted for conventional histology and
      ultrastructural examination. Our study shows that electron microscopy is
      necessary to complete the histological examinations, especially to define early
      stages of kidney diseases (minimal changes disease, epithelial tubular
      pathologies, tubular basement membrane and glomerular basement membrane changes).
      Electron microscopy can be more accurate in defining the level of focal lesion,
      and permits discrimination between different clinical and pathological
      alterations such as fibrillary deposits. In conclusion, transmission electron
      microscopy associated with clinical, histological, histochemical and
      immunological examinations, is an essential method for diagnosis and prognosis of
      renal disease.

PMID- 19094016
TI  - Quantitative HRTEM analysis of FIB prepared specimens.
AB  - The preparation of good transmission electron microscopy specimens with minimum
      milling damage can be very complicated, especially from a specific area in a
      sample. Therefore, a novel approach for transmission electron microscopy specimen
      preparation using a focused ion beam system is proposed, based on the use of low
      energy (5 kV)Ga ions and a low incident ion angle (approximately 1 degree ) from
      a thickness of approximately 500 nm until the sample is electron transparent.
      Transmission electron microscopy specimens prepared by this method have
      significantly less irradiation damage, demonstrated by successful quantitative
      high-resolution transmission electron microscopy conducted on sapphire from data
      acquired using an aberration-corrected field emission gun transmission electron
      microscopy. Quantitative analysis was conducted by iterative digital image
      matching. The accuracy and sensitivity of the matching process is discussed.

PMID- 19094017
TI  - Micromorphology of trichomes of Thymus malyi (Lamiaceae).
AB  - Micromorphological, ultrastructural and morphometric investigations of the
      trichomes of Thymus malyi were carried out using a light microscope, a scanning
      electron microscope and a transmission electron microscope. Unbranched non
      glandular trichomes, peltate and capitate glandular trichomes were described. The
      leaves of Thymus malyi bear non-glandular and glandular trichomes on both sides.
      Estimates of the volume density (i.e. their volume fraction per unit volume) of
      non-glandular trichomes were higher as compared to volume density of peltate and
      capitate glandular trichomes. Estimates of the number of these trichomes per area
      on sections showed that the capitate trichomes were the most abundant.
      Ultrastructural analyses of cell inner structure have shown numerous
      mitochondria, big nuclei and plastids with lipid globules and starch grains.

PMID- 19094018
TI  - Identification and characterization of a new zirconium hydride.
AB  - Zirconium alloys are currently used in nuclear power plants where they are
      susceptible to hydrogen pick-up. Hydride precipitation may occur when the
      hydrogen solubility limit is reached. Various Zr hydride phases, gamma, delta and
      epsilon have been identified since the 1950s. Combining electron precession
      microdiffraction, electron energy loss spectroscopy and ab initio electronic
      calculations, a new Zr hydride named zeta has been identified and characterized.
      It belongs to the trigonal crystal system with space group P3 m1 and it is fully
      coherent with the alphaZr matrix.

PMID- 19094019
TI  - Use of atomic force microscopy (AFM) for microfabric study of cohesive soils.
AB  - Microfabric reflects the imprints of the geologic and stress history of the soil
      deposit, the depositional environment and weathering history. Many investigators
      have been concerned with the fundamental problem of how the engineering
      properties of clay depend on the microfabric, which can be defined as geometric
      arrangement of particles within the soil mass. It is believed that scanning
      electron microscopy (SEM) and transmission electron microscopy (TEM) are the only
      techniques that can reveal particle arrangements of clayey soils directly;
      however, current research introduces a novel and more advanced technique, atomic
      force microscopy, to evaluate the microfabric of cohesive materials. The atomic
      force microscopy has several advantages over SEM/TEM for characterizing cohesive
      particles at the sub-micrometre range by providing 3D images and 2D images with Z
      information used in quantitative measurements of soil microfabric using SPIP
      software, and having the capability of obtaining images in all environments
      (ambient air, liquids and vacuums). This paper focuses on the use of atomic force
      microscopy technique to quantify the microfabric of clayey soils by developing
      the criteria for average and maximum values of angle of particle orientation
      within the soil mass using proposed empirical equations for intermediate and
      extreme microfabrics (dispersed, flocculated).

PMID- 19094021
TI  - Morphology of the fertilizable mature egg in the Acanthopagrus latus, A.
      schlegeli and Sparus sarba (Teleostei: perciformes: sparidae).
AB  - Through appropriate scanning electron microscope (SEM) processing, the shape and
      the surface structures of just-mature eggs are preserved integrally for
      observation and measuring to guarantee accurate comparison and prediction on the
      phylogenetic relationships among three species of teleost, i.e. Acanthopagrus
      latus, Acanthopagrus schlegeli and Sparus sarba of Sparidae. Eggs in all three
      species can be categorized as type III eggs. Specifically, a regular pattern is
      found in the arrangement of micropyle and its surrounding pore canals from the
      inspected surface structures of the mature eggs in three species. Other than
      these similarities in egg surface structures, several differences in micropyle
      structures, micropyle region and size of pore canals are also observed in eggs of
      respective species. Comprehension and accurate data are statistically computed
      and analyzed through hierarchical cluster analysis to provide solid species
      specific evidences and standardized empirical reference for accurate species
      identification and phylogeny determination.

PMID- 19094020
TI  - Ex vivo characterization of human atherosclerotic iliac plaque components using
      cryo-imaging.
AB  - We characterized atherosclerotic plaque components with a novel cryo-imaging
      system in lieu of standard histological methods commonly used for imaging
      validation and research endpoints. We aim to accurately identify plaque tissue
      types from fresh cadaver specimens rapidly (less than 5 h) in three dimensions
      for large specimens (up to 4 cm vessel segments). A single-blind validation study
      was designed to determine sensitivity, specificity and inter-rater agreement
      (Fleiss' Kappa) of cryo-imaging tissue types with histology as the gold standard.
      Six naive human raters identified 344 tissue type samples in 36 cryo-image sets
      after being trained. Tissue type sensitivities are as follows: greater than 90%
      for adventitia, media-related, smooth muscle cell ingrowth, external elastic
      lamina, internal elastic lamina, fibrosis, dense calcification and haemorrhage;
      greater than 80% for lipid and light calcification; and greater than 50% for
      cholesterol clefts. Specificities were greater than 95% for all tissue types. The
      results demonstrate convincingly that cryo-imaging can be used to accurately
      identify most tissue types. If the cryo-imaging data are entered into
      visualization software, three-dimensional renderings of the plaque can be
      generated to visualize and quantify plaque components.

PMID- 19094022
TI  - Applicability of the energy dispersive x-ray microanalysis for quantification of
      irregular calcium deposits on fruit and leaf cuticles.
AB  - In our studies, we evaluated the relation between CaCl(2) concentration and the
      scanning electron microscope-energy dispersive x-ray microanalysis parameters,
      net intensity, peak/background and standardized percentage of atoms and
      percentage of weight after application of single microdroplets on enzymatically
      isolated tomato fruit cuticles and apple seedling leaves. After analysis, the
      Ca/Cl ratio was calculated and the area ultimately covered with Ca and Cl within
      the droplet spread area determined. According to our findings, all evaluated
      parameters were influenced by both droplet volume and calcium chloride
      concentration, whereas Pearson's analysis revealed a strong correlation between
      net intensity and area ultimately covered by Ca or Cl, respectively. Simple
      linear regressions for net intensity, peak/background and Ca/Cl ratio showed
      variable determination coefficients (R(2)) ranging between 0.49 and 0.79.
      Multiple regression equations comprising net intensity, Ca/Cl ratio and deposit
      area were established to estimate the amount of calcium present on the cuticles.
      Equation slopes depended on droplet volumes, with determination coefficients of
      0.89 and 0.81 for 0.5 and 1.0-microL droplets, respectively. The importance of
      the physicochemical properties of the spray solution was exploited in another
      study where a hydrophobic or a hydrophilic adjuvant was added to a 10 g L(-1)
      CaCl(2) solution, which was applied to apple seedling leaves. The addition of
      adjuvants increased values of net intensity and peak/background, which correlated
      significantly with the area covered by calcium. The importance of the methodology
      for studies on the interaction between leaf applied fertilizers (also extended to
      agrochemicals) and the characteristics of target surfaces is discussed.

PMID- 19094023
TI  - An algorithm for extracting the network geometry of three-dimensional collagen
      gels.
AB  - The geometric structure of a biopolymer network impacts its mechanical and
      biological properties. In this paper, we develop an algorithm for extracting the
      network architecture of three-dimensional (3d) fluorescently labeled collagen
      gels, building on the initial work of Wu et al., (2003). Using artificially
      generated images, the network extraction algorithm is then validated for its
      ability to reconstruct the correct bulk properties of the network, including
      fiber length, persistence length, cross-link density, and shear modulus.

PMID- 19094024
TI  - Virtual histology by means of high-resolution X-ray CT.
AB  - Micro-CT is a non-destructive technique for 3D tomographic investigation of an
      object. A 3D representation of the internal structure is calculated based on a
      series of X-ray radiographs taken from different angles. The spatial resolution
      of current laboratory-used micro-CT systems has come down over the last years
      from a few tens of microns to a few microns. This opens the possibility to
      perform histological investigations in 3D on a virtual representation of a
      sample, referred to as virtual 3D histology. The advantage of micro-CT based
      virtual histology is the immediate and automated 3D visualization of the sample
      without prior slicing, sample preparation like decalcification, photographing and
      aligning. This not only permits a drastic reduction in preparation time but also
      offers the possibility to easily investigate objects that are difficult to slice.
      This article presents results that were obtained on punch biopsies of horse skin,
      (dental) alveolus of ponies and chondro-osseous samples from the tarsus of foals
      studied with the new high resolution micro-CT set-up (HRXCT) at the Ghent
      University (Belgium) (http://www.ugct.ugent.be). This state-of-the-art set-up
      provides a 1 micron resolution and is therefore ideally suited for a direct
      comparison with standard light microscopy-based histology.

PMID- 19094025
TI  - Effect of plant growth regulators on leaf anatomy of the has mutant of
      Arabidopsis thaliana.
AB  - In this study, the effect of plant growth regulators on leaf morphogenesis of the
      recessive T-DNA insertion mutant of Arabidopsis thaliana was analyzed. The morpho
      anatomical analysis revealed that leaves of the has mutant are small and narrow,
      with lobed blades and disrupted tissue organization. When has plants were grown
      on the medium supplied with plant growth regulators: benzylaminopurine (BAP) or
      ethylene precursor, 1-aminocyclopropane-1-carboxylic acid (ACC), the leaf anatomy
      was partially restored to the wild type, although plants still exhibited
      morphological abnormalities.

PMID- 19094026
TI  - Morphological characteristics and mycelial compatibility of different Mycogone
      perniciosa isolates.
AB  - The major disease of the cultivated mushroom Agaricus bisporus Lange (Imb) in
      Serbian mushroom farms is wet bubble caused by the fungus Mycogone perniciosa
      (Magnus) Delacr. In this study we report the morpho-physiological characteristics
      and inter-relationships between colonies of five isolates of M. perniciosa. The
      results suggest that mycelial compatibility could serve as an additional
      parameter for a more reliable determination of different pathotypes of M.
      perniciosa.

PMID- 19094028
TI  - Combined FTIR and SEM-EDS study of Bi2O3 doped ZnO-SnO2 ceramics.
AB  - The effects of Bi(2)O(3) addition on the phase composition, microstructure and
      optical properties of ZnO-SnO(2) ceramics were investigated. Starting powders of
      ZnO and SnO(2) were mixed in the molar ratio 2:1. After adding Bi(2)O(3) (1.0
      mol.%) this mixture was mechanically activated for 10 min in a planetary ball
      mill, uniaxially pressed and sintered at 1300 degrees C for 2 h. Far-infrared
      reflection spectra were measured (100-1000 cm(-1)). To investigate the occurred
      differences in FTIR spectra, the Bi(2)O(3)-doped sample was examined more
      carefully with a Perkin-Elmer FTIR spectrometer (Perkin Elmer, Waltham, MA, USA)
      connected with a Perkin-Elmer FTIR microscope and itemized points of interest
      were also studied with SEM-EDS.

PMID- 19094027
TI  - Glucose-dependent insulinotropic polypeptide-producing K cells in dexamethasone
      treated rats.
AB  - Some studies indicate that diabetes mellitus exerts an influence on the
      gastrointestinal tract and its diffuse neuroendocrine system (DNES) in regard to
      cellular density and neuroendocrine content. Since there is no data about
      relationship between experimentally induced non-insulin-dependent (type 2)
      diabetes mellitus (NIDDM) on the gut K cells, the aim of our study was to
      investigate immunohistochemical, stereological and ultrastructural changes of rat
      K cells after 12 days of dexamethasone treatment. Twenty male Wistar rats aged 30
      days were given daily intraperitoneally 2 mg kg(-1) dexamethasone (group DEX, 10
      rats) or saline (group C, 10 rats) for 12 days. Tissue specimens were obtained
      from each antrum with corpus and different parts of the small (SI) and large
      intestine (LI) of all animals. Immunohistochemistry was carried out using
      antisera against the GIP and insulin. Transmission electron microscopy was also
      used. Although, according to the literature data, rat K cells are present in the
      duodenum and jejunum and, to a lesser extent, in the ileum, in the present study
      we observed that those cells were abundant also in all parts of the LI. We
      observed generally that GIP-producing K cells were augmented in all parts of SI
      and decreased in the LI of DEX rats. Insulin immunoreactivity (ir) coexpressed
      with GIP-ir in K cells and was stronger in the SI of DEX rats as compared with C
      rats. We also found by electron microscopy that small intestinal K cells have
      features not only of GIP-secreted but also of insulin-secreted cells. We
      concluded that dexamethasone treatment caused proliferation of K cells in the rat
      SI, and simultaneously transformation of GIP-producing K cells to insulin
      synthesizing cells.

PMID- 19094029
TI  - Semi-thin sections of epoxy resin-embedded mouse embryos in morphological
      analysis of whole mount in situ RNA hybridization.
AB  - Descriptive morphological studies are often combined with gene expression pattern
      analyses. Unembedded vibratome or cryotome sections are compatible with in situ
      RNA hybridization, but spatial resolution is rather low for precise microscopic
      studies necessary in embryology. Therefore, use of plastic embedding media, which
      allow semi-thin and ultra-thin sectioning for light and electron microscopy,
      could be an important advantage. This work suggested a new approach based on the
      whole mount hybridization of mouse embryos and subsequent epoxy resin embedding.
      Epoxy resin allowed serial sectioning of semi-thin sections with preserved in
      situ RNA hybridization signal, which was a necessary prerequisite for precise
      morphological analysis of embryo development.

PMID- 19094030
TI  - Levels of plant cell wall structural organization revealed by atomic force
      microscopy.
AB  - We used an atomic force microscope to image cell wall isolated from needles of
      Serbian spruce tree and that synthesized from cell wall components. We also
      observed the structure of lignin model polymer (DHP), as a best substitute for
      the natural lignin. A tendency of aggregate formation was observed in all
      samples. Cell wall was revealed as a laminated fibrous structure. General
      organization is similar in both isolated and synthesized cell wall samples, with
      dominating globular motifs arranged regularly as rods and forming cavities. The
      synthesized cell wall has a more regular structural organization than isolated
      cell wall. The dimensions of individual globular aggregates and pores differed
      between the two samples. DHP showed a similar, regular organization, with
      globular aggregates and holes. Globules and pores are smaller in size than the
      corresponding structures in both the isolated and synthesized cell walls. Such
      modular organization of cell walls may have a physiological role in response to
      the external mechanical stress caused to plant cells.

PMID- 19094031
TI  - Morphological changes of poly(DI-lactide-co-glycolide) nano-particles containing
      ascorbic acid during in vitro degradation process.
AB  - Poly(DL-lactide-co-glycolide) powder composed of uniform particles with the mean
      particle size in the range of 110-170 nm was obtained from commercial granules.
      Ascorbic acid in different concentrations was encapsulated into the poly(DL
      lactide-co-glycolide) particles. Degradation of the latter in terms of
      morphological changes in the physiological solution was followed. Within a period
      of 2 months, the particles completely degrade and all the ascorbic acid is
      released. The samples were characterized by ultraviolet spectroscopy and scanning
      electron microscopy.

PMID- 19094032
TI  - Early effects of gamma rays and protons on human melanoma cell viability and
      morphology.
AB  - The effects of irradiation with gamma rays and protons on HTB140 human melanoma
      cell morphology and viability were analyzed. Exponentially growing cells were
      irradiated close to the Bragg peak maximum of the 62-MeV proton beam, as well as
      with (60)Co gamma rays, with doses ranging from 8 to 24 Gy. The overall cell
      morphology was unchanged 6 and 48 h after gamma irradiation, also showing a
      relatively weak cell-inactivation level. After exposure to proton beam,
      considerable changes in cell morphology followed by stronger cell inactivation
      were achieved. Proliferation capacity of irradiated cells significantly decreased
      in both experimental set-ups. Higher ionization level of protons with respect to
      gamma rays, representing the main physical difference between these two types of
      radiation, was also revealed on the cell membrane level through larger pro
      apoptotic capacity of protons.

PMID- 19094033
TI  - Hydrogen storage properties of MgH2-diatomite composites obtained by high-energy
      ball milling.
AB  - To investigate the effects of specific porous microstructure of diatomite on the
      hydrogen storage properties of MgH(2), a two-step preparation was carried out.
      The first step was decrepitation of MgH(2) particle size during 10 h of milling.
      The second step was additional 1 h of milling with diatomite. The microstructure
      and phase composition of materials was characterized by X-ray diffraction,
      whereas the powder morphology and degree of additive dispersion were analyzed by
      scanning electron microscopy. The hydrogen desorption behaviour of nanocomposites
      was investigated by differential scanning calorimetry. The results show that
      addition of porous diatomite structure leads to decrease in desorption
      temperature, since there was no other effect that can have an influence on
      kinetics, such as formation of the metastable gamma-phase, reduction of oxides to
      the native metal and/or homogeneous dispersion of the catalyst. This indicates
      that the microstructure of added material plays the main role in the enhancement
      of desorption properties of composites.

PMID- 19094034
TI  - Erythrophagosomal haemolytic degradative pathway in rat brown adipocytes induced
      by hyperinsulinaemia: an ultrastructural study.
AB  - The phagocytosis and degradation of erythrocytes were studied in brown adipose
      tissue of experimentally hyperinsulinaemic rats. We found that insulin induces
      intensive erythrophagocytosis by brown adipocytes and their degradation by
      haemolytic pathway. Ultrastuctural study revealed that haemolytic degradation of
      erythrophagosomes was characterized by progressive and uniform decrease of
      erythrocyte matrix density. At the beginning of the degradative process small,
      clear vesicles resembling primary lysosomes were visible inside the
      erythrophagosome. With time, the erythrocyte structure totally disappeared and
      transformed into a fine, granular material within the erythrophagosomal vacuole.
      Finally, the erythrocyte membrane detached from the phagosomal and clumped into
      the vacuolar space forming one or several small myelin-like figures. In
      conclusion, brown adipocytes are capable of performing intensive
      erythrophagocytic activity when brown adipose tissue is stimulated and blood flow
      is enhanced. The molecular basis for favouring a haemolytic instead of more
      common granular erythrophagosomal degradative pathway remains unknown.

PMID- 19094035
TI  - The influence of bonding agents in improving interactions in composite
      propellants determined using image analysis.
AB  - Binder-oxidizer interactions in rocket composite propellants can be improved
      using adequate bonding agents. In the present work, the effectiveness of
      different 1,3,5-trisubstituted isocyanurates was determined by stereo and
      metallographic microscopy and using the software package Image-Pro Plus. The
      chemical analysis of samples was performed by a scanning electron microscope
      equipped for energy dispersive spectrometry.

PMID- 19094036
TI  - Effect of cold compression on precipitation and conductivity of an Al-Li-Cu
      alloy.
AB  - Transmission electron microscopy has been used to investigate the effect of
      increasing the degree of deformation applied by cold compression on the ageing
      kinetics and electrical conductivity response of an Al-Li-Cu alloy containing Mg
      and Ag. When cold compressed greater than 3%, the increased dislocation density
      accelerates the widespread precipitation of the T(1) phase resulting in an
      enhanced age hardening response. The lengthening rate of T(1) precipitates is
      also reduced in this cold compressed condition owing to the reduced local solute
      supersaturation, a result of the widespread precipitation of T(1) plates. Cold
      compression by less than 3% does not increase the age hardening response, and the
      precipitation of GP zones/theta'' appears to be suppressed. Precipitation of the
      T(1) phase is also not significantly enhanced compared with that of the more than
      3% cold compressed conditions. The anomalous decrease in electrical conductivity
      is associated with the nucleation and growth of the T(1) phase. Strain fields
      around T(1) precipitates combined with the increased volume fraction of T(1) are
      thought to be the cause of the anomalous conductivity behaviour.

PMID- 19094037
TI  - Effects of the Ar ions pre-amorphization of Si substrate on interface mixing of
      Fe/Si bilayers.
AB  - Ion beam mixing of Fe/Si bilayers, induced by 100 keV (40)Ar ions at room
      temperature was investigated. Rutherford backscattering spectroscopy (RBS),
      atomic force microscopy (AFM), scanning electron microscopy (SEM) and
      transmission electron microscopy (TEM) were applied for structural
      characterization. The main focus of this study was on the influence of the
      substrate structure on interface mixing. The influence of the substrate structure
      is due to the two classes of irradiated bilayers, Fe thin films deposited on
      crystalline or pre-amorphized Si substrates. An about 76% higher efficiency of
      atomic transport across the pre-amorphized Fe/a-Si interface as compared to that
      of Fe/c-Si bilayers was observed.

PMID- 19094038
TI  - Nitric oxide regulates mitochondrial re-modelling in interscapular brown adipose
      tissue: ultrastructural and morphometric-stereologic studies.
AB  - As a complex, cell-specific process that includes both division and clear
      functional differentiation of mitochondria, mitochondriogenesis is regulated by
      numerous endocrine and autocrine factors. In the present ultrastructural study,
      in vivo effects of L-arginine-nitric oxide (NO)-producing pathway on
      mitochondriogenesis in interscapular brown adipose tissue (IBAT) were examined.
      For that purpose, adult Mill Hill hybrid hooded rats were receiving L-arginine, a
      substrate of NO synthases (NOSs), or N(omega)-nitro-L-arginine methyl ester (L
      NAME), an inhibitor of NOSs, as drinking liquids for 45 days. All experimental
      groups were divided into two sub-groups - acclimated to room temperature and
      cold. IBAT mitochondria were analyzed by transmission electron microscopy and
      stereology. L-Arginine treatment acted increasing the number of mitochondrial
      profiles per cell profile, as well as volume fraction of mitochondria per cell
      volume in animals maintained at room temperature. Cold-induced enhancement of
      number of mitochondrial profiles per cell profile was additionally increased in L
      arginine-treated rats. Ultrastructural examinations of L-arginine-treated cold
      acclimated animals clearly demonstrated thermogenically active mitochondria
      (larger size, lamellar, more numerous and well-ordered cristae in their
      profiles), which however were inactive in L-arginine-receiving animals kept at
      room temperature (small mitochondria, tubular cristae). By contrast, L-NAME
      treatment of rats acclimated to room temperature induced mitochondrial
      alterations characterized by irregular shape, short disorganized cristae and
      megamitochondria formation. These results showed that NO is a necessary factor
      for mitochondrial biogenesis and that it acts intensifying this process, but NO
      alone is not a sufficient stimulus for in vivo induction of mitochondriogenesis
      in brown adipocytes.

PMID- 19094039
TI  - Maternal dexamethasone treatment reduces ovarian follicle number in neonatal rat
      offspring.
AB  - Elevated glucocorticoid levels in the gravid female circulation affect a number
      of endocrine functions in the fetuses and neonates. The aim of this study was to
      examine the effects of maternal dexamethasone (Dx) administration during late
      pregnancy on the ovaries of neonatal offspring. On the 16th day of pregnancy,
      experimental dams received subcutaneously 1.0 mg Dx/kg b.w., followed by 0.5 mg
      Dx/kg b.w./day on the 17th and 18th days of gestation. The control gravid females
      received the same volume of saline vehicle. Left ovaries from 5-day-old female
      pups were stereologically analyzed. The ovary volumes were estimated using
      Cavalieri's principle. The number of healthy and atretic primordial and primary
      follicles was estimated using a fractionator-physical dissector method. The
      number of secondary follicles was determined by exact counts of every fourth
      section encompassing whole cross-sections of the ovary. The ovary volume was
      significantly decreased (by 44.4%; P < 0.05) in the group of female pups from Dx
      treated mothers comparing to the controls. The numbers of healthy primordial and
      atretic follicles were 38.8% (P < 0.05) and 50.9% (P < 0.05), respectively,
      reduced in the ovaries of pups from the Dx-treated mothers, when compared with
      the control values. There were 53.4% (P < 0.05) fewer healthy primary and 41.8%
      (P < 0.05) fewer healthy secondary follicles as well. The numbers of atretic
      primary and secondary follicles were reduced by 60.0% (P < 0.05) and 61.7% (P <
      0.05), respectively. It can be concluded that fetal exposure to glucocorticoids
      decreased the pool of non-growing follicles in the neonatal ovary, whereas the
      processes of folliculogenesis and atresia remained unaffected.

PMID- 19094040
TI  - Photothermal microscopy: a step from thermal wave visualization to spatially
      localized thermal analysis.
AB  - The calculation of photothermal response detected by a photothermal microscope is
      presented. By using a technique based on Green's functions and integral
      transforms, a model for laser-induced temperature distribution functions has been
      derived. The mathematical method for solution of inverse problem is proposed. It
      suggests that photothermal microscopy, besides imaging subsurface of solids, has
      the potential for quantitative thermal analysis of various samples.

PMID- 19094041
TI  - Comparison of single-particle analysis and electron tomography approaches: an
      overview.
AB  - Three-dimensional structure of a wide range of biological specimens can be
      computed from images collected by transmission electron microscopy. This
      information integrated with structural data obtained with other techniques (e.g.,
      X-ray crystallography) helps structural biologists to understand the function of
      macromolecular complexes and organelles within cells. In this paper, we compare
      two three-dimensional transmission electron microscopy techniques that are
      becoming more and more related (at the image acquisition level as well as the
      image processing one): electron tomography and single-particle analysis. The
      first one is currently used to elucidate the three-dimensional structure of
      cellular components or smaller entire cells, whereas the second one has been
      traditionally applied to structural studies of macromolecules and macromolecular
      complexes. Also, we discuss possibilities for their integration with other
      structural biology techniques for an integrative study of living matter from
      proteins to whole cells.

PMID- 19094042
TI  - Morphology and viscoelastic properties of sealing materials based on EPDM rubber.
AB  - In this applicative study, the ratio of active and inactive filler loadings was
      the prime factor for determining the dynamic-mechanical behaviour of ethylene
      propylene-diene monomer rubbers. Scanning electron microscopy was used to study
      the structure of reinforced dense and microcellular elastomeric materials. The
      effects of filler and blowing agent content on the morphology of composites were
      investigated. Microcellular samples cured in salt bath show smaller cells and
      uniform cell size compared with samples cured in hot air. Dynamic-mechanical
      thermal analysis showed appreciable changes in the viscoelastic properties by
      increasing active filler content, which could enable tailoring the material
      properties to suit sealing applications.

PMID- 19094043
TI  - Influence of substrate orientation on the morphology and orientation of LaNiO3
      thin films.
AB  - LaNiO(3) thin films were successfully prepared by a chemical method from citrate
      precursors. The LNO precursor solution was spin-coated onto Si (100) and Si (111)
      substrates. To obtain epitaxial or highly oriented films, the deposited layers
      were slowly heated in a gradient thermal field, with a heating rate of 1 degrees
      min(-1), and annealed at 700 degrees C. The influence of different substrate
      orientations on the thin film morphology was investigated using atomic force
      microscopy and X-ray diffraction analysis. Well-crystallized films with grains
      aligned along a certain direction were obtained on both substrates. Films
      deposited on both substrates were very smooth, but with a different grain size
      and shape depending on the crystal orientation. Films deposited on Si (100) grew
      in the (110) direction and had elongated grains, whereas those on Si (111) grew
      in the (211) direction and had a quasi-square grain shape.

PMID- 19094044
TI  - Fractographic analysis of fatigue damage in 7000 aluminium alloys.
AB  - In this paper, an attempt is made to correlate the fatigue damage in 7000
      aluminium alloys with different impurity contents to the microstructural features
      and to explain their interdependence through fractographic observations. The
      Paris constants of these alloys in the form of hot-forged plates subjected to the
      overaged T73 temper are evaluated and differences in the fatigue crack growth
      rate described by striation spacing measurements. Scanning electron microscopy
      analysis of fatigue fracture surfaces revealed that the type and morphological
      parameters of coarse intermetallic particles play a critical role in fatigue
      crack growth behaviour. The elemental distribution determined by means of energy
      dispersive spectroscopy analysis showed that the fractured particles accelerating
      the crack advances are larger particles of Fe-rich phases. The fatigue crack
      growth rate increases considerably with increasing amounts of these particles.
      The smaller eta, S and Mg(2)Si particles contribute beneficially to fatigue life.

PMID- 19094045
TI  - Surface roughness of ultra-thin silver films sputter deposited on a glass.
AB  - Silver was sputter deposited on a glass with a thin film thickness ranging from
      10 to 80 nm. Scanning tunnelling microscopy was used to study the morphology of
      the obtained Ag-glass surfaces and to estimate the surface roughness. An equation
      for the surface roughness of the thin film was evaluated using parameters related
      to the thin film features: the surface roughness of the substrate, the
      compressibility of the thin film and the film thickness. The experimental results
      were fitted using the evaluated equation, and the conditions favouring lower or
      higher surface roughness were analyzed.

PMID- 19094046
TI  - Particle size analysis: 90Y and 99mTc-labelled colloids.
AB  - Colloidal particle size is an important characteristic to consider when choosing
      a radiopharmaceutical for diagnosis and therapeutic purposes in nuclear medicine.
      Photon correlation spectroscopy (PCS) and transmission electron microscopy (TEM)
      were used to determine the particle-size distribution of (90)Y- and (99m)Tc
      labelled antimony trisulfide (Sb(2)S(3)) and tin colloids (Sn-colloid). (90)Y
      Sb(2)S(3) and (99m)Tc-Sb(2)S(3) were found to have a diameter of 28.92 +/- 0.14
      and 35.61 +/- 0.11 nm, respectively, by PCS. By TEM, (90)Y-Sb(2)S(3) particles
      were measured to be 14.33 +/- 0.09 nm. (90)Y-labelled Sn colloid were found to
      exist with a d(v(max1)) of 805 nm and a d(v(max2)) of 2590 nm, by PCS, whereas
      (99m)Tc-Sn colloid was shown to have more than 80% of radioactive particles of
      approximately 910 nm by PCS. For (90)Y-labelled Sb(2)S(3) and Sn colloid, a
      comparison of TEM and PCS indicates that these techniques found significantly
      different mean diameters. TEM has an excellent resolution necessary for
      radiocolloid particle-sizing analysis, and it is a desirable size-measuring
      technique because it is more reliable than PCS.

PMID- 19094047
TI  - Transition temperature and fracture mode of as-castand austempered ductile iron.
AB  - The ductile to brittle transition temperature is a very important criterion that
      is used for selection of materials in some applications, especially in low
      temperature conditions. For that reason, in this paper transition temperature of
      as-cast and austempered copper and copper-nickel alloyed ductile iron (DI) in the
      temperature interval from -196 to +150 degrees C have been investigated. The
      microstructures of DIs and ADIs were examined by light microscope, whereas the
      fractured surfaces were observed by scanning electron microscope. The ADI
      materials have higher impact energies compared with DIs in an as-cast condition.
      In addition, the transition curves for ADIs are shifted towards lower
      temperatures. The fracture mode of Dls is influenced by a dominantly pearlitic
      matrix, exhibiting mostly brittle fracture through all temperatures of testing.
      By contrast, with decrease of temperature, the fracture mode for ADI materials
      changes gradually from fully ductile to fully brittle.

PMID- 19094048
TI  - Moisture and gamma-ray irradiation effects on the mechanical properties of carbon
      fibre-reinforced plastics.
AB  - The effects of gamma-irradiation and moisture absorption on the mechanical
      properties of carbon fibres-epoxy resin composites were studied. The properties
      dominated by the matrix and fibre-matrix interface (interlaminar and in-plane
      shear strength) were measured at room temperature using standard tests. These
      tests were carried out before and after exposures to gamma irradiation and before
      and after immersion in water at 80 degrees C during 21 days. The dosage of gamma
      irradiation was up to 11.7 MGy. The micrographs of surfaces fractured in
      performed tests were observed on a scanning electron microscope. They were
      analyzed with consulting the stated effects on mechanical properties and the
      measured values of the glass transition temperature of tested coupons before and
      after irradiation and immersion in water. The obtained results show that moisture
      and irradiation, if they act one after the other, have a significant influence on
      the degradation of matrix-dominated mechanical properties of the tested carbon
      epoxy composite.

PMID- 19094049
TI  - Comparison of light and fluorescence microscopy for xylem analysis in tomato
      pedicels during fruit development.
AB  - The xylem hydraulic connection between shoot and fruits has previously been
      investigated, but contradictory conclusions were drawn about the presence of a
      flow resistance barrier in the pedicel. In this paper we were studying effect of
      the drought on the functional xylem vessels in the pedicels of tomato fruit.
      Commercial tomato genotype was grown in cabinet conditions under two watering
      regimes (full and deficit irrigation). An aqueous solution of eosin Y were used
      to visualize the path of water movement through tomato fruit pedicel and
      fluorescence microscopy observations were done on transversal and longitudinal
      sections. Dye uptake studies suggested that in well watered plants and in plants
      exposed to drought, a large majority of xylem vessels are not functional in water
      transport. Reduced-irrigation treatment significantly altered number and width of
      functional xylem elements in the fruit pedicel, especially in the abscission
      zone. This indicates that drought modifies xylem architecture and, thus,
      environmentally produced change in the hydraulic property of pedicel may affect
      fruit development.

PMID- 19094050
TI  - Modelling and experimental investigations of thin films of Mg phosphorus-doped
      tungsten bronzes obtained by ultrasonic spray pyrolysis.
AB  - In this study, the synthesis of thin films of Mg phosphorus doped tungsten
      bronzes (MgPTB; MgHPW(12)O(40).29H(2)O) by the self-assembly of nano-structured
      particles of MgPTB obtained using the ultrasonic spray pyrolysis method was
      investigated. As the precursor, MgPTB, prepared by the ionic exchange method, was
      used. Nano-structured particles of MgPTB were obtained using the ultrasonic spray
      pyrolysis method. The nano-structure of the particles used as the building blocks
      in the MgPTB thin film were investigated experimentally and theoretically,
      applying the model given in this article. The obtained data for the mean particle
      size and their size distribution show a high degree of agreement. These
      previously tailored particles used for the preparation of thin films during the
      next synthesis step, by their self-assembly over slow deposition on a silica
      glass substrate, show how it is possible to create thin MgPTB films under advance
      projected conditions of the applied physical fields with a fully determined
      nanostructure of their building block particles, with a relatively small
      roughness and unique physical properties.

PMID- 19094051
TI  - Investigation of properties of electrochemically synthesized iron oxide nano
      powders.
AB  - Nano-sized powders of iron oxides have been synthesized electrochemically at
      temperatures in the range of 295-361 K, and current densities in the range of 200
      1000 mA dm(-2). The structure and morphology of the powders were investigated by
      X-ray diffraction and scanning electron and transmission electron microscopy
      techniques. Their infrared absorption spectra, specific heat C(p)(T) and magnetic
      susceptibility chi(T) temperature dependences are also determined. The obtained
      powders consist of two phases, each possessing distinguished characteristics: the
      one formed of large plates and the other of whiskers. By appropriate adjustment
      of the synthesis conditions, it is possible to change features and relative
      abundances of the two phases, and that way to control morphology and other powder
      properties. Relaxation and transformation of the phases under external influences
      was also investigated, and the optimal procedure for preparation and
      stabilization of iron oxide nano-sized powders with desired characteristics was
      established.

PMID- 19094052
TI  - Structure and morphology of Mg-Al-Fe-mixed oxides derived from layered double
      hydroxides.
AB  - The influences of the nature and the extent of M(III) ion substitution on the
      structure, morphology and surface properties of layered double hydroxides, LDHs
      [Mg(1-x) M(III)(x)(OH)(2)](CO(3))(x/n).mH(2)O, M(III) being Al or/and Fe and x=
      M(III)/[(Mg+M(III)], and derived mixed oxides were investigated. Three series: Mg
      Al, Mg-Al-Fe and Mg-Fe were synthesized using low supersaturation co
      precipitation method at constant pH, with different Mg : Al : Fe ratio and x in
      the wide range from 0.15 to 0.7 in order to obtain complex, multi-phase systems
      with disordered structure, developed surface area, acid-base and redox properties
      favourable for catalytic application. The morphology of LDHs and their derived
      mixed oxides did not change considerably although pronounced changes in
      structural and surface properties occur by thermal decomposition. The increase in
      Al amount, as well as the deviation of M(III) content from the optimal range for
      the single LDH phase synthesis, causes the formation of smaller particles and
      decrease of mixed oxide crystallite size. The nature and amount of M(III)
      influence the development of surface area, after thermal treatment, depending
      mainly on the presence of smaller mesopores, not visible by scanning electron
      microscope. Although the particle size has no considerable influence on the value
      of the surface area, it was observed that the samples with smaller particles (Mg
      Al and Mg-Al-Fe series) have also higher surface area compared with the samples
      with larger particles (Mg-Fe series).

PMID- 19094053
TI  - Microstructural characterization of mechanically activated ZnO powders.
AB  - In this paper, changes of microstructural characteristics of disperse systems
      during mechanical activation of zinc oxide (ZnO) have been investigated. ZnO
      powder was activated by grinding in a planetary ball mill in a continuous regime
      in air during 300 min at the basic disc rotation speed of 320 rpm and rotation
      speed of bowls of 400 rpm but with various balls-to-powder mass ratios. During
      ball milling in a planetary ball mill, initial ZnO powder suffered high-energy
      impacts. These impacts are very strong, and large amounts of microstructural and
      structural defects were introduced in the milled powders. The morphology and
      dispersivity of particles and agglomerates of all powders were investigated by
      scanning electron microscopy and scanning transmission electron microscopy. The
      specific surface area of initial ZnO powder was determined as 3.60 m(2) g(-1) and
      it increased to 4.42 m(2) g(-1) in mechanically activated powders. An increase of
      the ball-to-powder mass ratio led to a decrease of particle dimensions as well as
      increased the tendency for joining into quite compact agglomerates, that is
      aggregates, compared with the very loose, soft initial agglomerates. The obtained
      results pointed out that activation of ZnO powders produces a highly disperse,
      nano-scaled mixture of small particles, that is crystallites with sizes in the
      range of 10-40 nm. Most of these particles are in the form of aggregates with
      dimensions of 0.3-0.1 mum. The crystallite and aggregate size strongly depend on
      milling conditions, that is ball-to-powder mass ratio, as shown in this
      investigation.

PMID- 19094055
TI  - Pre-synaptic GABA receptors inhibit glutamate release through GIRK channels in
      rat cerebral cortex.
AB  - Neuronal G protein-gated inwardly rectifying potassium (GIRK) channels mediate
      the slow inhibitory effects of many neurotransmitters post-synaptically. However,
      no evidence exists that supports that GIRK channels play any role in the
      inhibition of glutamate release by GABA(B) receptors. In this study, we show for
      the first time that GABA(B) receptors operate through two mechanisms in nerve
      terminals from the cerebral cortex. As shown previously, GABA(B) receptors
      reduces glutamate release and the Ca(2+) influx mediated by N-type Ca(2+)
      channels in a mode insensitive to the GIRK channel blocker tertiapin-Q and
      consistent with direct inhibition of this voltage-gated Ca(2+) channel. However,
      by means of weak stimulation protocols, we reveal that GABA(B) receptors also
      reduce glutamate release mediated by P/Q-type Ca(2+) channels, and that these
      responses are reversed by the GIRK channel blocker tertiapin-Q. Consistent with
      the functional interaction between GABA(B) receptors and GIRK channels at nerve
      terminals we demonstrate by immunogold electron immunohistochemistry that pre
      synaptic boutons of asymmetric synapses co-express GABA(B) receptors and GIRK
      channels, thus suggesting that the functional interaction of these two proteins,
      found at the post-synaptic level, also occurs at glutamatergic nerve terminals.

PMID- 19094056
TI  - ABC transporters, cytochromes P450 and their main transcription factors:
      expression at the human blood-brain barrier.
AB  - We have established the expression patterns of the genes encoding ATP-binding
      cassette (ABC) transporters and cytochromes P450 (CYPs) at the adult human blood
      brain barrier (BBB) using isolated brain microvessels and cortex biopsies from
      patients with epilepsia or glioma. Microves synaptophysin (neurons) and neuron
      glial antigen 2 (NG2) (pericytes). ABCG2 [breast cancer resistance protein
      (BCRP)] and ABCB1 (MDR1) were the main ABC transporter genes expressed in
      microvessels, with 20 times more ABCG2 and 25 times more ABCB1 in microvessels
      than in the cortex. The CYP1B1 isoform represented over 80% of all the CYPs genes
      detected in microvessels. There were 14 times more CYP1B1 in microvessels than in
      the cortex, showing that CYP1B1 is mainly expressed at the BBB. p-glycoprotein
      (ABCB1), BCRP (ABCG2) and CYP1B1 proteins were found in microvessels by western
      blotting. The expression of genes encoding three transcription factors [pregnane
      xenobiotic receptor (PXR), constitutive androstane receptor (CAR), aryl
      hydrocarbon receptor (AhR)] was also investigated. The AhR gene, involved in the
      regulation of CYP1B1 expression, was highly expressed in brain microvessels,
      whereas PXR and CAR genes were almost undetected. This detailed pattern of ABC
      and CYPs gene expression at the human BBB provides useful information for
      understanding how their substrates enter the brain.

PMID- 19094054
TI  - Notch: from neural development to neurological disorders.
AB  - Notch is an integral membrane protein that functions as receptor for ligands such
      as jagged and delta that are associated with the surface of neighboring cells.
      Upon ligand binding, notch is proteolytically cleaved within its transmembrane
      domain by presenilin-1 (the enzymatic component of the gamma-secretase complex)
      resulting in the release of a notch intracellular domain which translocates to
      the nucleus where it regulates gene expression. Notch signaling plays multiple
      roles in the development of the CNS including regulating neural stem cell (NSC)
      proliferation, survival, self-renewal and differentiation. Notch is also present
      in post-mitotic neurons in the adult CNS wherein its activation influences
      structural and functional plasticity including processes involved in learning and
      memory. Recent findings suggest that notch signaling in neurons, glia, and NSCs
      may be involved in pathological changes that occur in disorders such as stroke,
      Alzheimer's disease and CNS tumors. Studies of animal models suggest the
      potential of agents that target notch signaling as therapeutic interventions for
      several different CNS disorders.

PMID- 19094058
TI  - Stimulation of delta opioid receptors located in substantia nigra reticulata but
      not globus pallidus or striatum restores motor activity in 6-hydroxydopamine
      lesioned rats: new insights into the role of delta receptors in parkinsonism.
AB  - The delta opioid peptide (DOP) receptor has been proposed as a target in the
      symptomatic therapy of Parkinson's disease. However, the circuitry underlying the
      antiparkinsonian action of DOP receptor agonists and their site of action have
      never been adequately investigated. Systemic administration of the DOP receptor
      agonist (+)-4-[(alphaR)-alpha-(2S,5R)-allyl-2,5-dimethyl-1-piperazinyl)-3-methoxy
      benzyl]-N-N-diethylbenzamide (SNC-80) attenuated akinesia/bradykinesia and
      improved motor activity in 6-hydroxydopamine hemilesioned rats. Opposite effects
      were produced by the selective DOP receptor antagonist naltrindole (NTD),
      suggesting that endogenous enkephalins tonically sustain movement under
      parkinsonian conditions. Microdialysis revealed that SNC-80 reduced GABA release
      in globus pallidus (GP) while NTD elevated it. Moreover, SNC-80 reduced GABA and
      glutamate release in substantia nigra reticulata (SNr) whereas NTD reduced GABA
      without affecting glutamate release. The bar test coupled to microdialysis showed
      that perfusion with NTD in SNr but not GP or striatum prevented the antiakinetic
      effect of systemic SNC-80 and its neurochemical correlates. Consistently,
      microinjections of SNC-80 into SNr or bicuculline in GP attenuated parkinsonian
      like symptoms while SNC-80 microinjections in GP or striatum were ineffective.
      This study demonstrates that nigral DOP receptors mediate antiparkinsonian
      actions of SNC-80 and challenges the common view that DOP receptor agonists
      solely attenuate parkinsonism via pallidal mechanisms.

PMID- 19094057
TI  - Amperometric measurements of catecholamine release from single vesicles in MN9D
      cells.
AB  - MN9D cells have been used as a successful model to investigate dopamine
      pharmacology and to test the specific effects of drugs for the treatment of
      Parkinson's disease. However, quantitative measurements of quantal release from
      these cells have not been carried out. In this work, we used amperometry to
      investigate catecholamine release from MN9D cells. Amperometric events were
      observed in both undifferentiated and differentiated (butyric acid-treated)
      cells. An increase in quantal size and half-width was observed for differentiated
      cells versus undifferentiated cells; however, the number of events per cell and
      the amplitude remained constant. In transmission electron microscopy images, no
      obvious cluster of small synaptic vesicles was observed, and large dense-core
      vesicles were present in the cell body of undifferentiated cells; however, after
      differentiation, vesicles were concentrated in the cell processes. In
      differentiated cells, l-DOPA caused an increase in quantal size and half-width,
      which could be blocked by the vesicular monoamine transporter inhibitor,
      reserpine.

PMID- 19094059
TI  - Chronic voluntary ethanol intake hypersensitizes 5-HT(1A) autoreceptors in
      C57BL/6J mice.
AB  - Alcoholism is a complex disorder involving, among others, the serotoninergic (5
      HT) system, mainly regulated by 5-HT(1A) autoreceptors in the dorsal raphe
      nucleus. 5-HT(1A) autoreceptor desensitization induced by chronic 5-HT reuptake
      inactivation has been associated with a decrease in ethanol intake in mice. We
      investigated here whether, conversely, chronic ethanol intake could induce 5
      HT(1A) autoreceptor supersensitivity, thereby contributing to the maintenance of
      high ethanol consumption. C57BL/6J mice were subjected to a progressive ethanol
      intake procedure in a free-choice paradigm (3-10% ethanol versus tap water; 21
      days) and 5-HT(1A) autoreceptor functional state was assessed using different
      approaches. Acute administration of the 5-HT(1A) receptor agonist ipsapirone
      decreased the rate of tryptophan hydroxylation in striatum, and this effect was
      significantly larger (+75%) in mice that drank ethanol than in those drinking
      water. Furthermore, ethanol intake produced both an increased potency (+45%) of
      ipsapirone to inhibit the firing of 5-HT neurons, and a raise (+35%) in 5-HT(1A)
      autoreceptor-mediated stimulation of [(35)S]GTP-gamma-S binding in the dorsal
      raphe nucleus. These data showed that chronic voluntary ethanol intake in
      C57BL/6J mice induced 5-HT(1A) autoreceptor supersensitivity, at the origin of a
      5-HT neurotransmission deficit, which might be causally related to the addictive
      effects of ethanol intake.

PMID- 19094061
TI  - Diacylglycerol analogues activate second messenger-operated calcium channels
      exhibiting TRPC-like properties in cortical neurons.
AB  - The lipid diacylglycerol (DAG) analogue 1-oleoyl-2-acetyl-sn-glycerol (OAG) was
      used to verify the existence of DAG-sensitive channels in cortical neurons
      dissociated from E13 mouse embryos. Calcium imaging experiments showed that OAG
      increased the cytosolic concentration of Ca(2+) ([Ca(2+)]i) in nearly 35% of the
      KCl-responsive cells. These Ca(2+) responses disappeared in a Ca(2+)-free medium
      supplemented with EGTA. Mn(2+) quench experiments showed that OAG activated
      Ca(2+)-conducting channels that were also permeant to Ba(2+). The OAG-induced
      Ca(2+) responses were unaffected by nifedipine or omega-conotoxin GVIA (Sigma
      Aldrich, Saint-Quentin Fallavier, France) but blocked by 1-[beta-(3-(4
      Methoxyphenyl)propoxy)-4-methoxyphenethyl]-1H-imidazole hydrochloride (SKF)-96365
      and Gd(3+). Replacing Na(+) ions with N-methyl-D-glucamine diminished the
      amplitude of the OAG-induced Ca(2+) responses showing that the Ca(2+) entry was
      mediated via Na(+)-dependent and Na(+)-independent mechanisms. Experiments
      carried out with the fluorescent Na(+) indicator CoroNa Green showed that OAG
      elevated [Na(+)]i. Like OAG, the DAG lipase inhibitor RHC80267 increased
      [Ca(2+)]i but not the protein kinase C activator phorbol 12-myristate 13-acetate.
      Moreover, the OAG-induced Ca(2+) responses were not regulated by protein kinase C
      activation or inhibition but they were augmented by flufenamic acid which
      increases currents through C-type transient receptor potential protein family
      (TRPC) 6 channels. In addition, application of hyperforin, a specific activator
      of TRPC6 channels, elevated [Ca(2+)]i. Whole-cell patch-clamp recordings showed
      that hyperforin activated non-selective cation channels. They were blocked by SKF
      96365 but potentiated by flufenamic acid. Altogether, our data show the presence
      of hyperforin- and OAG-sensitive Ca(2+)-permeable channels displaying TRPC6-like
      properties. This is the first report revealing the existence of second messenger
      operated channels in cortical neurons.

PMID- 19094060
TI  - Allele-specific silencing of mutant Huntington's disease gene.
AB  - Huntington's disease (HD) is an autosomal-dominant neurodegenerative disorder
      caused by a poly-glutamine expansion in huntingtin, the protein encoded by the HD
      gene. PolyQ-expanded huntingtin is toxic to neurons, especially the medium spiny
      neurons of the striatum. At the same time, wild-type huntingtin has important -
      indeed essential - protective functions. Any effective molecular therapy must
      preserve the expression of wild-type huntingtin, while silencing the mutant
      allele. We hypothesized that an appropriate siRNA molecule would display the
      requisite specificity and efficacy. As RNA interference is incapable of
      distinguishing among alleles with varying numbers of CAG (glutamine) codons,
      another strategy is needed. We used HD fibroblasts in which the pathogenic
      mutation is linked to a polymorphic site: the Delta2642 deletion of one of four
      tandem GAG triplets. We silenced expression of the harmful Delta2642-marked polyQ
      expanded huntingtin without compromising synthesis of its wild-type counterpart.
      Following this success in HD fibroblasts, we obtained similar results with
      neuroblastoma cells expressing both wild-type and mutant HD genes. As opposed to
      the effect of depleting wild-type huntingtin, specifically silencing the mutant
      species actually lowered caspase-3 activation and protected HD cells under stress
      conditions. These findings have therapeutic implications not only for HD, but
      also for other autosomal dominant diseases. This approach has great promise: it
      may lead to personalized genetic therapy, a holy grail in contemporary medicine.

PMID- 19094062
TI  - Aggregate formation and toxicity by wild-type and R621C synphilin-1 in the
      nigrostriatal system of mice using adenoviral vectors.
AB  - Synphilin-1 was described as a protein interacting with alpha-synuclein and is
      commonly found in Lewy bodies, the pathological hallmark of Parkinson's disease
      (PD). Our group has previously described and characterized in vitro a mutation in
      the synphilin-1 gene (R621C) in PD patients. Providing the first characterization
      of synphilin-1 expression in an animal model, we here used adenoviral gene
      transfer to study the effects of wild-type (WT) and R621C synphilin-1 in
      dopaminergic neurons in mouse brain. As synphilin-1 is commonly used to trigger
      aggregation of alpha-synuclein in cell culture, we investigated not only non
      transgenic C57Bl/6 mice but also A30P-alpha-synuclein transgenic animals. Both WT
      synphilin-1 and R621C synphilin-1 led to the formation of Thioflavine-S positive
      inclusions in C57Bl/6 mice and degeneration of dopaminergic neurons in the
      substantia nigra. R621C synphilin-1 induced more aggregate formation than WT
      synphilin-1 in A30P-alpha-synuclein transgenic mice, consistent with the role of
      the R621C mutation as a susceptibility factor for PD. Synphilin-1 expression may
      be used to improve current mouse models of PD, as it induced both the formation
      of aggregates and degeneration of dopaminergic neurons, two core characteristics
      of PD that have not been well reproduced with expression of alpha-synuclein.

PMID- 19094063
TI  - Bi-directional modulation of fast inhibitory synaptic transmission by leptin.
AB  - The hormone leptin has widespread actions in the CNS. Indeed, leptin markedly
      influences hippocampal excitatory synaptic transmission and synaptic plasticity.
      However, the effects of leptin on fast inhibitory synaptic transmission in the
      hippocampus have not been evaluated. Here, we show that leptin modulates GABA(A)
      receptor-mediated synaptic transmission onto hippocampal CA1 pyramidal cells.
      Leptin promotes a rapid and reversible increase in the amplitude of evoked
      GABA(A) receptor-mediated inhibitory synaptic currents (IPSCs); an effect that
      was paralleled by increases in the frequency and amplitude of miniature IPSCs,
      but with no change in paired pulse ratio or coefficient of variation, suggesting
      a post-synaptic expression mechanism. Following washout of leptin, a persistent
      depression (inhibitory long-lasting depression) of evoked IPSCs was observed.
      Whole-cell dialysis or bath application of inhibitors of phosphoinositide 3 (PI
      3)-kinase or Akt prevented leptin-induced enhancement of IPSCs indicating
      involvement of a post-synaptic PI 3-kinase/Akt-dependent pathway. In contrast,
      blockade of PI 3-kinase or Akt activity failed to alter the ability of leptin to
      induce inhibitory long-lasting depression, suggesting that this process is
      independent of PI 3-kinase/Akt. In conclusion these data indicate that the
      hormone leptin bi-directionally modulates GABA(A) receptor-mediated synaptic
      transmission in the hippocampus. These findings have important implications for
      the role of this hormone in regulating hippocampal pyramidal neuron excitability.

PMID- 19094064
TI  - Doublecortin induces mitotic microtubule catastrophe and inhibits glioma cell
      invasion.
AB  - Doublecortin (DCX) is a microtubule (MT) binding protein that induces growth
      arrest at the G2-M phase of cell cycle in glioma and suppresses tumor xenograft
      in immunocompromised hosts. DCX expression was found in neuronal cells, but
      lacking in glioma cells. We tested the hypothesis that DCX inhibits glioma U87
      cell mitosis and invasion. Our data showed that DCX synthesizing U87 cells
      underwent mitotic MT spindle catastrophe in a neurabin II dependent pathway.
      Synthesis of both DCX and neurabin II were required to induce apoptosis in U87
      and human embryonic kidney 293T cells. In DCX expressing U87 cells, association
      of phosphorylated DCX with protein phosphatase-1 (PP1) in the cytosol disrupted
      the interaction between kinesin-13 and PP1 in the nucleus and yielded
      spontaneously active kinesin-13. The activated kinesin-13 caused mitotic MT
      catastrophe in spindle checkpoint. Phosphorylated-DCX induced depolymerization of
      actin filaments in U87 cells, down-regulated matrix metalloproteinases-2 and -9,
      and inhibited glioma U87 cell invasion in a neurabin II dependent pathway. Thus,
      localization of the DCX-neurabin II-PP1 complex in the cytosol of U87 tumor cells
      inhibited PP1 phosphatase activities leading to anti-glioma effects via (1)
      mitotic MT spindle catastrophe that blocks mitosis and (2) depolymerization of
      actin that inhibits glioma cell invasion.

PMID- 19094065
TI  - A novel reciprocal and biphasic relationship between membrane cholesterol and
      beta-secretase activity in SH-SY5Y cells and in human platelets.
AB  - Research into the cause of Alzheimer's disease (AD) has identified strong
      connections to cholesterol. Cholesterol and cholesterol esters can modulate
      amyloid precursor protein (APP) processing, thus altering production of the Abeta
      peptides that deposit in cortical amyloid plaques. Processing depends on the
      encounter between APP and cellular secretases, and is thus subject to the
      influence of cholesterol-dependent factors including protein trafficking, and
      distribution between membrane subdomains. We have directly investigated
      endogenous membrane beta-secretase activity in the presence of a range of
      membrane cholesterol levels in SH-SY5Y human neuroblastoma cells and human
      platelets. Membrane cholesterol significantly influenced membrane beta-secretase
      activity in a biphasic manner, with positive correlations at higher membrane
      cholesterol levels, and negative correlations at lower membrane cholesterol
      levels. Platelets from individuals with AD or mild cognitive impairment (n = 172)
      were significantly more likely to lie within the negative correlation zone than
      control platelets (n = 171). Pharmacological inhibition of SH-SY5Y beta-secretase
      activity resulted in increased membrane cholesterol levels. Our findings are
      consistent with the existence of a homeostatic feedback loop between membrane
      cholesterol level and membrane beta-secretase activity, and suggest that this
      regulatory mechanism is disrupted in platelets from individuals with cognitive
      impairment.

PMID- 19094066
TI  - NF-kappaB p50/RelA and c-Rel-containing dimers: opposite regulators of neuron
      vulnerability to ischaemia.
AB  - Diverse nuclear factor-kappaB subunits mediate opposite effects of extracellular
      signals on neuron survival. While RelA is activated by neurotoxic agents, c-Rel
      drives neuroprotective effects. In brain ischaemia RelA and p50 factors rapidly
      activate, but how they associate with c-Rel to form active dimers and contribute
      to the changes in diverse dimer activation for neuron susceptibility is unknown.
      We show that in both cortical neurons exposed to oxygen glucose deprivation (OGD)
      and mice subjected to brain ischaemia, activation of p50/RelA was associated with
      inhibition of c-Rel/RelA dimer and no change p50/c-Rel. Targeting c-Rel and RelA
      expression revealed that c-Rel dimers reduced while p50/RelA enhanced neuronal
      susceptibility to anoxia. Activation of p50/RelA complex is known to induce the
      pro-apoptotic Bim and Noxa genes. We now show that c-Rel-containing dimers, p50/c
      Rel and RelA/c-Rel, but not p50/RelA, promoted Bcl-xL transcription. Accordingly,
      the OGD exposure induced Bim, but reduced Bcl-xL promoter activity and decreased
      the content of endogenous Bcl-xL protein. These findings demonstrate that within
      the same neuronal cell, the balance between activation of p50/RelA and c-Rel
      containing complexes fine tunes the threshold of neuron vulnerability to the
      ischaemic insult. Selective targeting of different dimers will unravel new
      approaches to limit ischaemia-associated apoptosis.

PMID- 19094067
TI  - No increased risk of hypoglycaemic episodes during 48 h of subcutaneous glucagon
      like-peptide-1 administration in fasting healthy subjects.
AB  - OBJECTIVE: It is uncertain whether the ability to avoid hypoglycaemia during
      fasting is preserved, and the risk of reactive hypoglycaemia after an oral
      glucose stimulus following a prolonged fasting period is increased at augmented
      glucagon-like peptide-1 (GLP-1) levels. DESIGN: A randomized, double-blind
      placebo-controlled cross-over study in eight healthy men to assess the safety, in
      terms of hypoglycaemia, of a continuously infused pharmacological dose of native
      GLP-1 during long-term fasting. After an overnight fast the fasting period
      continued for 48 h and was followed by a 3-h oral glucose tolerance test (OGTT).
      GLP-1(7-36 amide) or placebo was continuously infused subcutaneously and titrated
      to a dose of 4.8 pmol/kg per min. RESULTS: Two subjects in the GLP-1 group and
      one subject in the placebo group were withdrawn due to protocol specified plasma
      glucose (PG) < or = 2.8 mm and neuroglycopaenic symptoms. The infusion of GLP-1
      resulted in pharmacological levels of intact GLP-1. During the fasting period PG,
      insulin and C-peptide levels declined and glucagon, GH and free fatty acid (FFA)
      levels increased with no differences between GLP-1 and placebo. During OGTT
      circulating levels of insulin and C-peptide were higher with GLP-1 infusion.
      However, PG was similar during GLP-1 vs. placebo infusions. GLP-1 infusion
      increased norepinephrine and cortisol levels during OGTT. CONCLUSION: The counter
      regulatory response during 48 h of subcutaneous GLP-1 infusion was preserved
      despite long-term fasting with no apparent increased risk of hypoglycaemic
      episodes. No reactive hypoglycaemia was observed when the fast was followed by an
      OGTT. Thus use of long-acting GLP-1 analogues may not increase the risk of
      hypoglycaemia.

PMID- 19094068
TI  - Effects of 18 months of L-T4 replacement in women with subclinical
      hypothyroidism.
AB  - CONTEXT: Some of the cardiovascular and renal abnormalities seen in overt
      hypothyroidism have also been reported in subclinical hypothyroidism (SCH). Short
      term L-T4 replacement in SCH improves cardiovascular risk markers and reduces
      carotid intima-media thickness (CIMT), a surrogate marker of atherosclerosis. The
      haemodynamic and renal effects of L-T4 replacement in SCH are poorly understood.
      OBJECTIVES: To compare cardiovascular risk factors and renal variables in women
      with SCH and normal women. To study the effects of L-T4 replacement in SCH
      subjects on these variables and on structural and functional changes in common
      carotid and brachial arteries. DESIGN: Fifty-six women with SCH before and after
      L-T4 replacement for 18 months and 56 normal women of similar age distribution
      were studied. Blood Pressure (BP), plasma lipids and homocysteine were measured
      and renal function evaluated [estimation of glomerular filtration rate (eGFR)
      using standard equations and measurement of serum Cystatin-C] in women with SCH
      before and after 18 months of l-T4, and in healthy women. CIMT and endothelial
      function (using brachial artery ultrasound) were studied before and after L-T4 in
      a subgroup of women with SCH. RESULTS: Systolic and diastolic BP, total
      cholesterol, triglyceride, LDL-cholesterol, lipoprotein(a) and homocysteine were
      greater in SCH (P < 0.05), and following L-T4 replacement decreased (P < 0.05) to
      levels that no longer differed from normal subjects. Estimated GFR was reduced
      and serum Cystatin-C increased (P < 0.05) in SCH. These variables also normalized
      following L-T4. Following L-T4 replacement the carotid artery baseline diameter
      increased by 7.1% and CIMT decreased by a mean value of 13%, while brachial
      artery diameter increased basally by 12.5% and following endothelium-dependent
      vasodilatation by 17.5% (P < 0.05). However, the increment following reactive
      hyperaemia did not differ before or following L-T4 replacement. CONCLUSION:
      Normalization of cardiovascular risk factors following L-T4 replacement in SCH
      potentially explains reduced CIMT. Increased carotid and brachial artery
      diameters and normalized eGFR indicates a haemodynamic effect of L-T4
      replacement, the importance of which requires further investigation.

PMID- 19094069
TI  - Androgenetic alopecia and insulin resistance in young men.
AB  - BACKGROUND: Epidemiological studies have associated androgenetic alopecia (AGA)
      with severe young-age coronary artery disease and hypertension, and linked it to
      insulin resistance. We carried out a case-control study in age- and weight
      matched young males to study the link between AGA and insulin resistance using
      the homeostasis model assessment of insulin resistance (HOMA-IR) index or
      metabolic syndrome clinical manifestations. METHODS: Eighty young males, 18-35
      years old, with AGA > or = stage III in the Hamilton-Norwood classification, and
      80 weight- and age-matched controls were included. Alopecia, glucose, serum
      insulin, HOMA-IR index, lipid profile and androgen levels, as well as metabolic
      syndrome criteria, were evaluated. RESULTS: The HOMA-IR index was significantly
      higher in cases than controls. Nonobese cases had a higher mean diastolic blood
      pressure and a more frequent family history of AGA than nonobese controls. A
      borderline difference in the HOMA-IR index was found in obese AGA cases vs. obese
      controls [P = 0.055, 95% confidence interval (CI) 2.36-4.20 vs. 1.75-2.73]. Free
      testosterone values were significantly higher in controls than cases, regardless
      of body mass index (BMI). A statistically significant additive effect for obesity
      plus alopecia was found, with significant trends for insulin, the HOMA-IR index,
      lipids and free testosterone when BMI and alopecia status were used to classify
      the participants. CONCLUSIONS: Our results support the recommendation for
      assessing insulin resistance and cardiovascular-related features and disorders in
      all young males with stage III or higher AGA, according to the Hamilton-Norwood
      classification.

PMID- 19094070
TI  - Effect of vardenafil on endothelial progenitor cells in hypogonadotrophic
      hypogonadal patients: role of testosterone treatment.
AB  - CONTEXT: Endothelial progenitor cells (EPCs) are bone marrow-derived cells
      required for endothelial repair. Circulating EPC concentration is low in
      conditions characterized by endothelial dysfunction but their number can be
      increased by treatment with phosphodiesterase-5 (PDE5) inhibitors. EPCs are also
      reduced in hypogonadal men and testosterone (T) treatment restores their
      concentration. OBJECTIVE: To evaluate the relationship between the effect of PDE5
      inhibitors and T on EPCs, we analysed the acute effect of vardenafil on the
      number of EPCs in hypogonadotrophic hypogonadal (HH) patients, before and after T
      treatment. DESIGN AND SETTING: A case-control study at a university andrology
      centre. PATIENTS: Fifteen HH subjects and 25 aged-matched controls. MAIN OUTCOME
      MEASURES: The number of circulating EPCs and progenitor cells (PCs) in HH
      patients was evaluated after acute vardenafil administration at baseline and
      after 6 months of T supplementation. RESULTS: At baseline, HH men had
      significantly lower numbers of PCs and EPCs with respect to controls and
      vardenafil administration had no effect on the number of these cells. After 6
      months of T treatment, all HH patients were eugonadal. With respect to baseline,
      PCs and EPCs were significantly higher and reached the levels observed in
      controls. Vardenafil administration in HH men at the end of T treatment induced a
      significant increase in PCs and EPCs in a manner similar to that in controls.
      CONCLUSIONS: This study showed that normal T levels are necessary to restore the
      responsiveness of EPCs to PDE5 inhibitors, suggesting that T positively modulates
      PDE5 in bone marrow.

PMID- 19094071
TI  - Increased arterial stiffness in nonobese women with polycystic ovary syndrome
      (PCOS) without comorbidities: one more characteristic inherent to the syndrome?
AB  - BACKGROUND: Polycystic ovary syndrome (PCOS) is associated with adverse metabolic
      effects. Some cardiovascular disease (CVD) risk markers are increased in women
      with PCOS. However, early markers of atherosclerosis are also associated with
      obesity and insulin resistance, which are related to PCOS. These markers may
      result either directly from PCOS or indirectly as a consequence of the
      comorbidities associated with the syndrome. CONTEXT: To assess the presence of
      early CVD markers in young, nonobese women with PCOS. PATIENTS: Forty women with
      PCOS and 50 healthy women with regular menstrual cycles, matched for age and body
      mass index (BMI). MEASUREMENTS: The following CVD markers were assessed by
      ultrasonography: common carotid artery (CCA) stiffness index (beta),
      distensibility and intima-media thickness (IMT), and brachial artery flow
      mediated dilatation (FMD). Inflammatory markers, including interleukin (IL)-6,
      tumour necrosis factor (TNF)-alpha, homocysteine, C-reactive protein (CRP),
      glycaemia, lipid profile and insulin, were also assessed. RESULTS: CCA beta was
      higher in PCOS than in control women (3.72 +/- 0.96 vs. 3.36 +/- 0.96, P = 0.04)
      and CCA distensibility was lower (0.31 +/- 0.08 vs. 0.35 +/- 0.09 mmHg(-1), P =
      0.02). Waist circumference, total testosterone and the Free Androgen Index (FAI)
      were higher in PCOS patients than in controls (78.2 +/- 10.0 vs. 71.5 +/- 7.2 cm,
      P = 0.001; 88.1 +/- 32.4 vs. 57.1 +/- 21.2 ng/dl, P < 0.01; 12.7 +/- 15.7%vs. 4.7
      +/- 2.3%, P < 0.01, respectively), while SHBG was reduced (37.9 +/- 19.1 vs. 47.8
      +/- 18.3 nmol/l, P = 0.01). The remaining variables did not differ between the
      groups. CONCLUSIONS: Young women with PCOS exhibit changes in vascular elasticity
      even in the absence of classical risk factors for CVD, such as hypertension and
      obesity.

PMID- 19094072
TI  - Growth hormone and prolactin response to ghrelin during the normal menstrual
      cycle.
AB  - OBJECTIVE: It has been suggested that exogenous oestradiol augments ghrelin
      induced growth hormone (GH) secretion in postmenopausal women. Whether endogenous
      oestrogens exert a similar effect during the normal menstrual cycle is not known.
      The aim of this study was to test the hypothesis that physiological changes in
      ovarian steroids during the normal menstrual cycle modulate GH and prolactin
      (PRL) response to ghrelin. DESIGN: Healthy women were studied in three phases of
      the normal menstrual cycle. PATIENTS: Ten healthy normally cycling women.
      MEASUREMENTS: A single dose of ghrelin (1 microg/kg) was administered
      intravenously in the early and late follicular phases and in the mid-luteal phase
      of the cycle. Saline was injected in the preceding cycle. Blood samples were
      taken before ghrelin or saline injection (time 0) and also at -15, 15, 30, 45,
      60, 75, 90 and 120 min. The GH and PRL responses were assessed. RESULTS: Serum
      oestradiol and progesterone concentrations showed the variations of a normal
      menstrual cycle. After ghrelin administration, in the three phases of the cycle,
      plasma ghrelin and serum GH and PRL levels increased rapidly, peaking at 30 min
      and declining gradually thereafter (P < 0.001). There were no significant
      differences in the hormone levels between the three phases at all time points. No
      changes in GH and PRL levels were seen after saline injection. CONCLUSIONS: These
      results demonstrate that GH and PRL responses to ghrelin do not change across the
      menstrual cycle. It is suggested that the action of ghrelin on the pituitary
      somatotrophs is modulated differentially by endogenous and exogenous ovarian
      steroids.

PMID- 19094073
TI  - The effect of growth hormone treatment on metabolic and cardiovascular risk
      factors is similar in preterm and term short, small for gestational age children.
AB  - CONTEXT: We previously reported that short, small for gestational age (SGA)
      children who were born preterm have a lower body fat percentage and a higher
      blood pressure, insulin secretion and disposition index than short SGA children
      born at term. Whether preterm birth also influences these parameters during GH
      treatment is unknown. OBJECTIVE: To compare blood pressure, insulin sensitivity,
      beta-cell function and body composition during 4 years of GH treatment, between
      preterm and term short SGA children. PATIENTS: A total of 404 prepubertal non-GH
      deficient short SGA children were divided into 143 preterm (< 36 weeks) and 261
      term children. OUTCOME MEASURES: Height, blood pressure (n = 404), body
      composition measured by dual energy X-ray absorptiometry (DXA) (n = 138) and
      insulin sensitivity and beta-cell function calculated from a frequent sampling
      intravenous glucose tolerance test (FSIGT) with tolbutamide (n = 74) or from the
      homeostasis model assessment of insulin resistance (HOMA-IR) (n = 204). RESULTS:
      In preterm and term children, GH treatment resulted in a similar decrease in
      systolic and diastolic blood pressure, body fat percentage, limb fat/total fat
      ratio and insulin sensitivity, and a similar increase in insulin secretion and
      disposition index. Lean body mass (LBM) corrected for gender and height increased
      in term children and did not change in preterm children. Multiple regression
      analysis revealed that this difference in GH effect on LBM was not associated
      with gestational age. CONCLUSION: The effect of GH treatment on metabolic and
      cardiovascular risk factors is similar in preterm and term short, SGA children.

PMID- 19094074
TI  - Significant tumour shrinkage after 12 months of lanreotide Autogel-120 mg
      treatment given first-line in acromegaly.
AB  - OBJECTIVE: To evaluate GH and IGF-I control and tumour shrinkage in newly
      diagnosed patients with acromegaly treated first-line with lanreotide-Autogel
      (ATG) 120 mg. Design Open, prospective. PATIENTS: Twenty-six patients (17 women,
      aged 31-70 years): eight enclosed and 12 extrasellar (eight invasive)
      macroadenomas and six microadenomas (one invasive). ATG 120 mg initially given
      every 4 weeks for 12 weeks; then intervals between injections increased to every
      6 or 8 weeks if GH levels were <or= 2.5 or < 1 microg/l (equal to 6.5 and 2.6
      mU/l), respectively. RESULTS: Final dosage was ATG 120 mg every 4 weeks in nine
      patients (34.6%), every 6 weeks in eight patients (30.8%) and every 8 weeks in
      the remaining nine patients (34.6%). After 12 months, both GH and IGF-I were
      controlled in 14 patients (53.8%). The mean tumour volume decreased from 1405 +/-
      1827 mm(3) at study entry to 960 +/- 1381 mm(3) after 6 months, and 799 +/- 1161
      mm(3) after 12 months (P < 0.0001). Overall tumour shrinkage was 35.8 +/- 28.1%
      after 6 months and 48.4 +/- 27.6% after 12 months. After 12 months, 20 patients
      (76.9%) achieved > 25% tumour shrinkage: 12 of 14 with controlled disease (85.7%)
      and 8 of 12 with noncontrolled disease (66.7%; P = 0.49). Hyperhydrosis,
      paresthesiae and arthralgias significantly reduced after treatment. No patient
      withdrew from the study because of adverse events. CONCLUSION: ATG 120 mg in
      newly diagnosed patients with acromegaly controls GH and IGF-I secretion in 53.8%
      and induces >or= 25% tumour shrinkage in 76.9% during a 12-month period. The
      treatment was associated with improvement of clinical symptoms and with a good
      safety profile.

PMID- 19094075
TI  - Assessment of thyroid function during the long course of Hashimoto's thyroiditis
      in children and adolescents.
AB  - CONTEXT: The prognosis of Hashimoto's thyroiditis (HT) in children and
      adolescents is not well known and studies reporting long-term outcome of the
      disease are scarce. OBJECTIVE: To assess the thyroid hormone status during long
      term follow-up and to establish the prognosis of children and adolescents with
      HT. PATIENTS: One hundred and twenty-nine patients with HT were re-evaluated for
      thyroid hormone status after a mean follow-up period of 50 months. RESULTS:
      Seventy-seven per cent of the euthyroid patients were still euthyroid, while
      21.1% of these patients became hypothyroid at the time of re-evaluation. However,
      69.5% of hypothyroid patients remained hypothyroid (overt or subclinical) and
      30.5% recovered. CONCLUSION: HT is a dynamic process. Thyroid functions can show
      variation during follow-up. Therefore, thyroid function tests should be repeated
      periodically to detect progression to hypothyroidism in initially euthyroid
      patients as well as reversibility of hypothyroidism.

PMID- 19094076
TI  - Predisposition to vitamin D deficiency osteomalacia and rickets in females is
      linked to their 25(OH)D and calcium intake rather than vitamin D receptor gene
      polymorphism.
AB  - BACKGROUND: Osteomalacia (OSM) and rickets are widely prevalent in developing
      countries especially in females. The factors associated with such predisposition
      are not known. OBJECTIVES: To identify nutritional, endocrine and genetic factors
      related to calcium and vitamin D metabolism that are associated with OSM/rickets
      in females. SUBJECTS AND METHODS: We studied 98 patients with OSM or rickets and
      their relatives including male and female sibs and parents (n = 221) for the
      presence of biochemical OSM {low serum 25-hydroxyvitamin D [25(OH)D], raised
      intact PTH (iPTH) and raised alkaline phosphatase} and associated nutritional and
      genetic factors. Polymerase chain reaction restriction fragment length
      polymorphism (PCR-RFLP) was used for genotyping vitamin D receptor (VDR) (BsmI
      and FokI) and PTH gene (BstBI and DraII) single nucleotide polymorphisms (SNPs)
      in 74 families. The differences in the factors associated with calcium and
      vitamin D among the different groups were analysed by analysis of variance
      (ANOVA). Logistic regression analysis and the transmission disequilibrium test
      (TDT) were carried out to assess association between nutritional and genetic
      factors, and the disease, respectively. RESULTS: Most of the patients were female
      (91.8%). The mean serum 25(OH)D level of the female patients was comparable to
      that of the female sibs (14.4 +/- 5.7 vs. 18.3 +/- 9.7 nmol/l). The frequency of
      biochemical OSM was fivefold higher in female than in male sibs (24.4%vs. 4.9%).
      Female sibs also had significantly lower 25(OH)D, dietary calcium intake and
      sunshine exposure than male sibs. The frequency of biochemical OSM was comparable
      between mothers and fathers. The odds of biochemical OSM in the family members
      was reduced by 11% per 15-min daily sunshine exposure [odds ratio (OR) = 0.89,
      95% confidence interval (CI) = 0.81-0.98, P = 0.02] and decreased by 20% per 100
      mg dietary calcium intake (OR = 0.80, 95% CI = 0.67-0.96, P = 0.02). VDR/PTH gene
      SNPs showed no association with OSM/rickets on TDT analysis. CONCLUSION: Among
      the immediate family members of patients with OSM/rickets, female sibs have
      features of biochemical OSM in up to 24.4%. Female sibs, unlike male sibs, share
      with patients features of markedly low serum 25(OH)D levels, poor dietary calcium
      intake and poor exposure to sunshine. Genetic factors such as VDR and PTH gene
      SNPs were not associated with OSM/rickets.

PMID- 19094077
TI  - Meniere's attacks occur in the inner ear with excessive vasopressin type-2
      receptors.
AB  - Meniere's disease is peculiar to humans and is characterised by episodic vertigo,
      fluctuating hearing loss and tinnitus, and attacks of the affliction occurring
      under conditions of stress. Its pathology was first revealed to be inner ear
      hydrops through temporal bone studies in 1938. Although subsequently proposed as
      a disorder of water metabolism in the inner ear, its pathogenesis remains
      unsolved. The present study aimed to assess the link between the inner ear
      pathology in Meniere's disease and vasopressin, an anti-diuretic stress hormone
      with a potential role in inner ear fluid homeostasis. Blood samples were obtained
      from Meniere's disease patients in the morning, before any surgical treatment, to
      examine plasma vasopressin (pAVP) levels, and then from inner ear tissue during
      surgical treatment, to examine vasopressin type-2 receptor (V2R) in the
      endolymphatic sac. pAVP and the relative V2R mRNA expression in the endolymphatic
      sac were examined using a real-time polymerase chain reaction. Relative cAMP
      activity in the endolymphatic sac was also examined using tissue culture and cAMP
      assay. Both pAVP (1.6-fold versus controls; P = 0.048) and inner ear V2R mRNA
      expression (41.5-fold versus controls; P = 0.022) were significantly higher in
      Meniere's patients. cAMP activity was basally up-regulated (2.1-fold versus
      controls) and cAMP sensitivity to vasopressin application was largely elevated
      (4.9-fold versus controls) in Meniere's patients. We conclude that, in the
      pathogenesis of inner ear hydrops, resulting in Meniere's attacks, elevation of
      pAVP levels (probably as a result of stress) may present as a matter of
      consequence, but susceptibility of the V2R-overexpressed and cAMP-hypersensitized
      inner ear to pAVP elevation might be essential as the basis of this disease.
      Further experimental and clinical studies are needed to better clarify the
      relationship between Meniere's disease and stress.

PMID- 19094078
TI  - In three brain regions central to maternal behaviour, neither male nor female
      Phodopus dwarf hamsters show changes in oestrogen receptor alpha distribution
      with mating or parenthood.
AB  - Oestrogen receptor (ER)alpha immunoreactivity in three brain regions relevant to
      maternal behaviour (medial preoptic area, bed nucleus of the stria terminalis and
      medial amygdala) was measured in two species of dwarf hamster that both mate
      during a postpartum oestrous but differ in expression of paternal behaviour. Male
      and female Phodopus campbelli and Phodopus sungorus were sampled as sexually
      naive adults, following mating to satiety, and as new parents. In all brain
      regions, females expressed higher levels of ER alpha than males. Species did not
      have an effect on ER alpha distribution except in the medial amygdala, where P.
      sungorus females had higher expression levels than all other groups. Behavioural
      status was not associated with altered ER alpha expression. These results were
      not expected for females and suggest that a primary activational role for
      oestrogen, acting through ER alpha in these regions, does not generalize to
      maternal behaviour in Phodopus. In males, these results are consistent with
      previous manipulations of the ER alpha ligand, oestrogen, and suggest that
      paternal behaviour in P. campbelli is likely to be regulated by developmental
      effects of oestrogen on the brain during early life (similar to Microtus
      ochrogaster), rather than through activation by oestrogen at the time of
      fatherhood (similar to Peromyscus californicus).

PMID- 19094079
TI  - Tibolone rapidly attenuates the GABAB response in hypothalamic neurones.
AB  - Tibolone is primarily used for the treatment of climacteric symptoms. Tibolone is
      rapidly converted into three major metabolites: 3 alpha- and 3beta-hydroxy (OH)
      tibolone, which have oestrogenic effects, and the Delta 4-isomer (Delta 4
      tibolone), which has progestogenic and androgenic effects. Because tibolone is
      effective in treating climacteric symptoms, the effects on the brain may be
      explained by the oestrogenic activity of tibolone. Using whole-cell patch clamp
      recording, we found previously that 17beta-oestradiol (E(2)) rapidly altered
      gamma-aminobutyric acid (GABA) neurotransmission in hypothalamic neurones through
      a membrane oestrogen receptor (mER). E(2) reduced the potency of the GABA(B)
      receptor agonist baclofen to activate G-protein-coupled, inwardly rectifying K(+)
      (GIRK) channels in hypothalamic neurones. Therefore, we hypothesised that
      tibolone may have some rapid effects through the mER and sought to elucidate the
      signalling pathway of tibolone's action using selective inhibitors and whole cell
      recording in ovariectomised female guinea pigs and mice. A sub-population of
      neurones was identified post hoc as pro-opiomelanocortin (POMC) neurones by
      immunocytochemical staining. Similar to E(2), we have found that tibolone and its
      active metabolite 3 beta OH-tibolone rapidly reduced the potency of the GABA(B)
      receptor agonist baclofen to activate GIRK channels in POMC neurones. The effects
      were blocked by the ER antagonist ICI 182 780. Other metabolites of tibolone (3
      alpha OH-tibolone and Delta 4-tibolone) had no effect. Furthermore, tibolone (and
      3 beta OH-tibolone) was fully efficacious in ER alpha knockout (KO) and ER beta
      KO mice to attenuate GABA(B) responses. The effects of tibolone were blocked by
      phospholipase C inhibitor U73122. However, in contrast to E(2), the effects of
      tibolone were not blocked by protein kinase C inhibitors or protein kinase A
      inhibitors. It appears that tibolone (and 3 beta OH-tibolone) activates
      phospholipase C leading to phosphatidylinositol bisphosphate metabolism and
      direct alteration of GIRK channel function. Therefore, tibolone may enhance
      synaptic efficacy through the G(q) signalling pathways of mER in brain circuits
      that are critical for maintaining homeostatic functions.

PMID- 19094080
TI  - A genomic analysis of subclinical hypothyroidism in hippocampus and neocortex of
      the developing rat brain.
AB  - Hypothyroidism during pregnancy and the early postnatal period has severe
      neurological consequences for the developing offspring. The impact of milder
      degrees of perturbation of the thyroid axis as encompassed in conditions of
      subclinical hypothyroidism and hypothyroxinemia, however, has not been
      established. The present investigation examined the effects of graded levels of
      hypothyroidism, from subclinical to severe, on global gene expression in the
      developing rodent brain. Thyroid hormone insufficiency was induced by
      administration of propylthiouracil (PTU) to pregnant rats via drinking water from
      gestational day 6 until sacrifice of pups prior to weaning. In the first study a
      specialised microarray, the Affymetrix Rat Neurobiology array RN_U34, was used to
      contrast gene expression in the hippocampus of animals exposed to 0 or 10 ppm (10
      mg/l) PTU, a treatment producing severe hypothyroidism. In the second study, a
      more complete genome array (Affymetrix Rat 230A) was used to compare gene
      expression in the neocortex and hippocampus of postnatal day (PN) 14 animals
      experiencing graded degrees of thyroid hormone insufficiency induced by delivery
      of 0, 1, 2 or 3 ppm PTU to the dam. Dose-dependent up- and down-regulation were
      observed for gene transcripts known to play critical roles in brain development
      and brain function. Expression levels of a subset of approximately 25 genes in
      each brain region were altered at a dose of PTU (1 ppm) that induced mild
      hypothyroxinemia in dams and pups. These data indicate that genes driving
      important developmental processes are sensitive to relatively modest
      perturbations of the thyroid axis, and that the level of gene expression is
      related to the degree of hormone reduction. Altered patterns of gene expression
      during critical windows of brain development indicate that thyroid disease must
      be viewed as a continuum and that conditions typically considered 'subclinical'
      may induce structural and functional abnormalities in the developing central
      nervous system.

PMID- 19094081
TI  - Photoperiod and testosterone interact to drive seasonal changes in kisspeptin
      expression in Siberian hamsters (Phodopus sungorus).
AB  - Kisspeptin, a neuropeptide product of the KiSS-1 gene, has recently been
      implicated in the regulation of seasonal breeding in a number of species,
      including Siberian hamsters. In this species, kisspeptin expression is reduced in
      the anteroventral periventricular nucleus (AVPV) following exposure to inhibitory
      day lengths, and exogenous kisspeptin activates the reproductive neuroendocrine
      axis of reproductively quiescent animals. Because sex steroids can impact
      kisspeptin expression, it is unclear whether changes in kisspeptin occur in
      direct response to photoperiodic cues or secondarily in response to changes in
      sex steroid concentrations resulting from the transition to reproductive
      quiescence. The present study aimed to assess the relative contributions of
      photoperiod and testosterone in regulating kisspeptin expression in Siberian
      hamsters. Animals housed in long or short day lengths for 8 weeks were either
      castrated or received sham surgeries. Half of the hamsters in each photoperiod
      were given testosterone to mimic long-day sex steroid concentrations. The results
      obtained indicate that kisspeptin neurones in the AVPV and arcuate nuclei were
      influenced by both photoperiod and testosterone. In the AVPV, removal of
      testosterone or exposure to inhibitory day lengths led to a marked reduction in
      kisspeptin-immunoreactive cells, and testosterone treatment increased cell
      numbers across conditions. Importantly, long-day castrates exhibited
      significantly more kisspeptin cells than short-day castrates or intact short-day
      animals with empty capsules, suggesting the influences of photoperiod,
      independent of gonadal steroids. In general, the opposite pattern emerged for the
      arcuate nuclei. Collectively, these data suggest a role for both gonadal
      dependent and independent (i.e. photoperiodic) mechanisms regulating seasonal
      changes in kisspeptin expression in Siberian hamsters.

PMID- 19094082
TI  - Death of hypothalamic astrocytes in poorly controlled diabetic rats is associated
      with nuclear translocation of apoptosis inducing factor.
AB  - Astrocytes in the hypothalamus of poorly controlled diabetic rats are reduced in
      number, due to increased apoptosis and decreased proliferation, and undergo
      morphological changes, including a decrease in projections. These changes are
      associated with modifications in synaptic proteins and most likely affect
      neuroendocrine signalling and function. The present study aimed to determine the
      intracellular mechanisms underlying this increase in hypothalamic cell death.
      Adult male Wistar rats were injected with streptozotocin (70 mg/kg, i.p) and
      controls received vehicle. Rats were killed at 1, 4, 6 and 8 weeks after diabetes
      onset (glycaemia > 300 mg/dl). Cell death, as detected by enzyme-linked
      immunosorbent assay, increased at 4 weeks of diabetes. Immunohistochemistry and
      terminal dUTP nick-end labelling (TUNEL) assays indicated that these cells
      corresponded to glial fibrillary acidic protein (GFAP) positive cells. No
      significant change in fragmentation of caspases 2, 3, 6, 7, 8, 9, or 12 was
      observed with western blot analysis. However, enzymatic assays indicated that
      caspase 3 activity increased significantly after 1 week of diabetes and decreased
      below control levels thereafter. In the hypothalamus, cell bodies lining the
      third ventricle, fibres radiating from the third ventricle and GFAP positive
      cells expressed fragmented caspase 3, with this labelling increasing at 1 week of
      diabetes. However, because no nuclear labelling was observed and this increase in
      activity did not correlate temporally with the increased cell death, this caspase
      may not be involved in astrocyte death. By contrast, nuclear translocation of
      apoptosis inducing factor (AIF) increased significantly in astrocytes in parallel
      with the increase in death and AIF was found in TUNEL positive cells. Thus,
      nuclear translocation of AIF could underlie the increased death, whereas
      fragmentation of caspase 3 could be associated with the morphological changes
      found in hypothalamic astrocytes of diabetic rats.

PMID- 19094083
TI  - Antagonists of the protein kinase A and mitogen-activated protein kinase systems
      and of the progestin receptor block the ability of vaginocervical/flank-perineal
      stimulation to induce female rat sexual behaviour.
AB  - Brief vaginocervical stimulation using a glass rod (VCS) combined with manual
      flank-perineal stimulation (FS) rapidly (within 5 min) induced both receptive and
      proceptive behavioural responses to males in ovariectomised, oestrogen-primed
      rats. This receptive-proceptive response to males, resulting from a single brief
      (5-s duration) instance of manual VCS + FS, declined markedly within 4 h.
      However, the decline was prevented if the females were mounted by males
      immediately after the manual VCS + FS and 2 h later. We tested the participation
      of the cAMP-dependent protein kinase A system and the mitogen-activated protein
      kinase (MAPK) system in the response to VCS + FS by infusing either 100 ng of Rp
      adenosine 3',5'-cyclic monophosphorothiate triethylamonium salt (a protein kinase
      A blocker) or 3.3 microg of PD98059 (a MAPK blocker) i.c.v. 15 min prior to VCS +
      FS. Both inhibitors blocked the ability of VCS + FS to induce the proceptive
      receptive responses to males at all testing intervals. In experiment 2, systemic
      administration of 5 mg of RU486 1 h before VCS + FS also blocked the ability of
      VCS + FS to induce the proceptive-receptive responses to males. The present
      findings suggest that both VCS + FS and mating stimuli provided by males release
      neurotransmitters and neuromodulators that trigger the protein kinase A and the
      MAPK signalling systems, which interact with the progestin receptor to rapidly
      (within 5 min) induce proceptive-receptive behaviour in females.

PMID- 19094084
TI  - Evaluation of endocrine profile, hypothalamic-pituitary-testis axis and semen
      quality in multiple sclerosis.
AB  - Several endocrine and sexual disturbances have been demonstrated in multiple
      sclerosis (MS) patients of both sexes. The endocrine profile, hypothalamic
      pituitary-testis (HPT) axis and semen quality were evaluated in male patients
      with MS. A total of 68 male MS patients aged 18 years or older were recruited.
      Forty-eight age-matched healthy male volunteers served as controls. All subjects
      underwent complete physical examination and routine semen analysis. Two blood
      samples were drawn from each participant at 15-min intervals for the
      determination of the resting levels of: luteinising-hormone (LH), follicle
      stimulating hormone (FSH), prolactin, testosterone, oestradiol and sex hormone
      binding globulin. The HPT axis was assessed using gonadotrophin-releasing hormone
      (GnRH) and human chorionic gonadotrophin tests. The mean basal serum levels for
      LH, FSH and testosterone in MS patients were significantly lower than the mean
      for normal controls (P = 0.01). The injection of GnRH analogue did not yield a
      significant increase in FSH and LH levels in the MS patients compared to normal
      controls (P = 0.001). Total sperm count, sperm motility and percent normal sperm
      morphology were lower in MS patients compared to controls. MS subjects with
      progressive disease had higher and more severe HPT axis abnormalities than that
      for patients with relapsing remitting MS. Most subjects with MS have
      hypogonadotrophic hypogonadism state and fertility impairment. It appears that
      the damage to HPT axis is both in pituitary and testicular levels. Further
      studies are needed to better elucidate the underlying pathophysiology of HPT axis
      dysregulation.

PMID- 19094086
TI  - Arginine vasotocin neuronal phenotypes among congeneric territorial and shoaling
      reef butterflyfishes: species, sex and reproductive season comparisons.
AB  - Arginine vasotocin (AVT) and the homologous arginine vasopressin (AVP)
      neuropeptides are involved in the control of aggression, spacing behaviour and
      mating systems in vertebrates, but the function of AVT in the regulation of
      social behaviour among closely-related fish species needs further clarification.
      We used immunocytochemical techniques to test whether AVT neurones show species,
      sex or seasonal differences in two sympatric butterflyfish sister species: the
      territorial monogamous multiband butterflyfish, Chaetodon multicinctus, and the
      shoaling polygamous milletseed butterflyfish, Chaetodon miliaris. The territorial
      species had larger AVT-immunoreactive (-ir) somata within the preoptic area, and
      higher AVT fibre densities within but not limited to the ventral telencephalon,
      medial and dorsal nucleus of the dorsal telencephalon, torus semicircularis, and
      tectum compared to the shoaling nonterritorial species. Furthermore, AVT-ir
      somata size and number did not differ among sexes or spawning periods in the
      territorial species, and showed only limited variation within the shoaling
      species. The distinct difference in AVT neuronal characteristics among species is
      likely to be independent of body size differences, and the lack of sex and
      seasonal variability is consistent with their divergent but stable social and
      mating systems. These phenotypic differences among species may be related to the
      influence of AVT on social spacing, aggression or monogamy, as reported for other
      fish, avian and mammalian models. The present study provides the first evidence
      for variation in vasotocin neural organisation in two congeneric and sympatric
      fish species with different social systems.

PMID- 19094085
TI  - Changes in prodynorphin gene expression and neuronal morphology in the
      hypothalamus of postmenopausal women.
AB  - Human menopause is characterised by ovarian failure, gonadotrophin hypersecretion
      and hypertrophy of neurones expressing neurokinin B (NKB), kisspeptin (KiSS)-1
      and oestrogen receptor (ER) alpha gene transcripts within the hypothalamic
      infundibular (arcuate) nucleus. In the arcuate nucleus of experimental animals,
      dynorphin, an opioid peptide, is colocalised with NKB, kisspeptin, ER alpha and
      progesterone receptors. Moreover, ovariectomy decreases the expression of
      prodynorphin gene transcripts in the arcuate nucleus of the ewe. Therefore, we
      hypothesised that the hypertrophied neurones in the infundibular nucleus of
      postmenopausal women would express prodynorphin mRNA and that menopause would be
      accompanied by changes in prodynorphin gene transcripts. In the present study, in
      situ hybridisation was performed on hypothalamic sections from premenopausal and
      postmenopausal women using a radiolabelled cDNA probe targeted to prodynorphin
      mRNA. Autoradiography and computer-assisted microscopy were used to map and count
      labelled neurones, measure neurone size and compare prodynorphin gene expression
      between premenopausal and postmenopausal groups. Neurones expressing dynorphin
      mRNA in the infundibular nucleus of the postmenopausal women were larger and
      exhibited hypertrophied morphological features. Moreover, there were fewer
      neurones labelled with the prodynorphin probe in the infundibular nucleus of the
      postmenopausal group compared to the premenopausal group. The number of dynorphin
      mRNA-expressing neurones was also reduced in the medial preoptic/anterior
      hypothalamic area of postmenopausal women without changes in cell size. No
      differences in cell number or size of dynorphin mRNA-expressing neurones were
      observed in any other hypothalamic region. Previous studies using animal models
      provide strong evidence that the changes in prodynorphin neuronal size and gene
      expression in postmenopausal women are secondary to the ovarian failure of
      menopause. Given the inhibitory effect of dynorphin on the reproductive axis,
      decreased dynorphin gene expression could play a role in the elevation in
      luteinising hormone secretion that occurs in postmenopausal women.

PMID- 19094088
TI  - Photoperiod-testicular-immune interaction in a seasonal breeder Indian palm
      squirrel Funambulus pennanti during the reproductively inactive and active
      phases.
AB  - The differential effect of long (LD; 16 : 8 h light/dark), short (SD; 10 : 14 h
      light/dark) and natural day length (NDL; 12 : 12 h light/dark) during the
      reproductively inactive (RIP) and active (RAP) phases was assessed in relation to
      immunity and reproductive function of a tropical rodent Funambulus pennanti. They
      presented high immunity and low testicular activity during RIP and an opposite
      during RAP. SD increased spleen and thymus weight, leukocyte and lymphocyte
      counts, cell mediated immunity [i.e. blastogenic response in terms of percentage
      stimulation ratio of splenocytes and thymocytes (when challenged with
      concanavalin A)] and delayed type hypersensitivity to oxazolone. SD during RIP
      increased the above mentioned parameters and reduced testes weight compared to
      NDL groups. During RAP, LD reduced all the immunological parameters when compared
      with NDL and SD experiencing groups of RIP and RAP phases. The LD group reduced
      the immunological parameters compared to RAP, suggesting that LD had always an
      inhibitory effect on immune status being independent of reproductive phases. The
      intensity of the stimulatory effects of SD and inhibitory effects of LD during
      both reproductive phases was significantly different. We exposed another set of
      squirrels to the above photoperiodic schedule for prolonged period (30 weeks)
      during RAP. A clear testicular refractoriness followed by immunorefractoriness
      was observed in the group experiencing SD and LD for 30 weeks. The
      photorefractoriness presented by the testes was inversely related to the
      immunorefractoriness. The peripheral melatonin level of those squirrels reflected
      the photoperiodic signal perceived by squirrels for immunomodulation and gonadal
      function, suggesting that immune system and gonadal function might have
      coevolved.

PMID- 19094089
TI  - Serotonergic and catecholaminergic interactions with co-localised dopamine
      melatonin neurones in the hypothalamus of the female turkey.
AB  - Serotonin and catecholamines (dopamine, norepinephrine, epinephrine) have
      important roles as neurotransmitters in avian reproduction, but their anatomical
      relationship to the neuroendocrine circuitry that regulates reproduction is
      poorly understood. Our previous studies have shown that co-localised dopamine
      melatonin (DA-MEL) neurones in the avian premammillary nucleus (PMM) are active
      during periods of photoresponsiveness and, therefore, are potentially
      photosensitive neurones. Because serotonergic and catecholaminergic
      neurotransmitters are important regulators of reproductive function in the female
      turkey, we hypothesised that the serotonergic/catecholaminergic neurones within
      the brainstem might interact with PMM DA-MEL neurones and constitute an important
      circuit for reproductive function. To examine this possible interaction, the
      retrograde fluorescent tract tracer, 1,1'dioctadecyl-3,3,3'3'
      tetramethyleindocarbocyanine perchlorate (DiI) was injected into the PMM, and
      combined with serotonin, tyrosine hydroxylase (TH), dopamine beta-hydroxylase
      (DBH) and phenyl N-methyltransferse (PNMT) immunocytochemistry to reveal
      neuroanatomical connections. Changes in the activities of serotonergic,
      dopaminergic, adrenergic and noradrenergic neuronal systems projecting to the PMM
      were measured at different reproductive states with in situ hybridisation (ISH)
      techniques, using tryptophan hydroxylase 2 (TPH2) and TH mRNA expression,
      respectively. Cells labelled with DiI were found in anatomically discrete areas
      in or near the hypothalamus and the brainstem. Double immunocytochemistry
      confirmed that there were serotonin, DBH and PNMT fibres in close apposition to
      DA-MEL neurones. TPH2 mRNA expression in serotonin neurones was found in several
      nuclei, and its most abundant mRNA expression was seen in the nucleus Locus
      ceruleus of laying and incubating hens. TH mRNA expression levels in the six
      catecholaminegic areas labelled with DiI was measured across the different
      reproductive states. In the nucleus tractus solitarius (adrenergic), the highest
      level of TH mRNA expression was found in photorefractory hens and the lowest
      level in incubating hens. These observed patterns of serotonin/catecholamine
      neuronal distribution and their variable interactions with PMM DA-MEL neurones
      during different reproductive states may offer a significant neuroanatomical
      basis for understanding the control of avian reproductive seasonality.

PMID- 19094090
TI  - Down-regulation of hypothalamic kisspeptin and its receptor, Kiss1r, mRNA
      expression is associated with stress-induced suppression of luteinising hormone
      secretion in the female rat.
AB  - Identification of kisspeptin (Kiss1) and its G protein-coupled receptor 54
      (Kiss1r) as an essential component of the hypothalamic-pituitary-gonadal (HPG)
      axis controlling gonadotrophin secretion raises the possibility that kisspeptin
      Kiss1r signalling may play a critical role in the transduction of stress-induced
      suppression of reproduction. We examined the effects of: (i) three different
      stressors, known to suppress pulsatile luteinising hormone (LH) secretion; (ii)
      corticotrophin-releasing factor (CRF); and (iii) corticosterone on Kiss1 and
      Kiss1r expression in key hypothalamic sites regulating gonadotrophin secretion:
      the medial preoptic area (mPOA) and arcuate nucleus (ARC). Ovariectomised
      oestrogen-replaced rats were implanted with i.v., subcutaneous or i.c.v.
      cannulae. Blood samples were collected at 5-min intervals for 5-6 h for detection
      of LH. Quantitative reverse transcriptase-polymerase chain reaction was used to
      determine Kiss1 and Kiss1r mRNA levels in brain punches of the mPOA and ARC
      collected 6 h after restraint, insulin-induced hypoglycaemia or
      lipopolysaccharide stress, or after i.c.v. administration of CRF, or acute or
      chronic subcutaneous administration of corticosterone. We observed down
      regulation of at least one component of the kisspeptin-Kiss1r signalling system
      by each of the stress paradigms within the mPOA and ARC. CRF decreased Kiss1 and
      Kiss1r expression in both the mPOA and ARC. Both acute and chronic stress levels
      of corticosterone resulted in a concomitant decrease in Kiss1 and an increase in
      kiss1r mRNA expression in the mPOA and ARC. This differential regulation of Kiss1
      and Kiss1r might account for the lack of effect corticosterone has on pulsatile
      LH secretion. Considering the pivotal role for kisspeptin-Kiss1r signalling in
      the control of the HPG axis, these results suggest that the reduced Kiss1-Kiss1r
      expression may be a contributing factor in stress-related suppression of LH
      secretion.

PMID- 19094091
TI  - Mating-induced neuroendocrine responses during pseudopregnancy in the female
      mouse.
AB  - Pseudopregnancy (PSP) is a neuroendocrine reflex triggered by vaginocervical
      stimulation similar to the neuroendocrine response of early pregnancy and is
      characterised by short-term neural activity, resulting in long-term
      neuroendocrine responses that cause repeated release of pituitary prolactin (PRL)
      over many days. PSP is a useful model to study how somatosensory input is
      transduced in the brain into neuroendocrine responses, and has been extensively
      characterised in rats. With increasing use of mice as an experimental model,
      however, and to allow use of transgenic mice to investigate mechanisms of this
      sensory response, it is important to characterise the principal neuroendocrine
      response of pseudopregnancy in this species. The present study aimed to examine
      the induction and neuroendocrine responses of PSP in mice using vasectomised stud
      males, to investigate mating-induced changes in vaginal cytology, uterine growth,
      and PRL secretion, and to map certain aspects of somatosensory transduction by
      assessing the neural activity marker FOS. Unlike the induction of pseudopregnancy
      in rats, which can be induced simply by multiple intromissions from a male or
      artificial mechanical stimulation of the cervix, PSP induction in mice required
      the receipt of an ejaculation from a male. In mice that received PSP-inducible
      mating stimuli, FOS expression was observed in a slightly different range of
      brain regions than has been observed in rats, with increases in the bed nucleus
      of the stria terminalis, medial preoptic area, and ventromedial hypothalamus, but
      not in limbic areas examined. Moreover, PSP mice expressed a single diurnal PRL
      surge on day 6 of PSP. Thus, the data demonstrate important species differences
      in the neuroendocrine mechanisms activated in response to a mating stimulus in
      mice compared with rats. A clear understanding of the species-specific response
      will be required in interpreting research into the reproductive biology of this
      species.

PMID- 19094092
TI  - Perinatal undernutrition modifies cell proliferation and brain-derived
      neurotrophic factor levels during critical time-windows for hypothalamic and
      hippocampal development in the male rat.
AB  - Maternal perinatal undernutrition (MPU) modifies the activity of the hypothalamic
      pituitary-adrenal axis and sensitises to the development of metabolic and
      cognitive adult diseases. Because the hypothalamus and hippocampus are involved
      in the regulation of neuroendocrine activity, energy metabolism and cognition, we
      hypothesised that a maternal 50% food restriction (FR50) from day 14 of pregnancy
      (E14) until postnatal day 21 (P21) would affect the development of these
      structures in male rat offspring. Protein and mRNA levels of brain-derived
      neurotrophic factor (BDNF) and cell proliferation [analysed by 5
      bromodeoxyuridine (BrdU) incorporation] were compared in both control and FR50
      rats from E21 to P22. Although the pattern of the evolution of BDNF concentration
      and cell proliferation throughout development was not strikingly different
      between groups, several disturbances at specific developmental stages were
      observed. FR50 rats exhibited a delayed increase of hippocampal BDNF content
      whereas, in the hypothalamus, BDNF level was augmented from E21 to P14 and
      associated, at this latter stage, with an increased mRNA expression of TRkB-T2.
      In both groups, a correlation between BDNF content and the number of BrdU
      positive cells was noted in the dentate gyrus, whereas opposite variations were
      observed in CA1, CA2 and CA3 layers, and in the arcuate and ventromedial nuclei.
      In the hippocampus, P15-FR50 rats showed an increased number of BrdU positive
      cells in all regions, whereas, at P22, a decrease was observed in the CA2. In the
      hypothalamus, between E21 and P8, MPU increases the number of BrdU positive cells
      in all regions analysed and, until P15, marked differences were noticed in the
      median eminence, the paraventricular nucleus and the arcuate nucleus. Taken
      together, the results obtained in the present study show that MPU changes the
      time course of production of BDNF and cell proliferation in specific hippocampal
      and hypothalamic areas during sensitive developmental windows, suggesting that
      these early perinatal modifications may have long-lasting consequences.

PMID- 19094093
TI  - Thyroid hormone receptor alpha plays an essential role in the normalisation of
      adult-onset hypothyroidism-related hypoexpression of synaptic plasticity target
      genes in striatum.
AB  - Thyroid hormone (TH) deficiency leads to molecular changes resulting in
      behavioural deficits. TH action is mediated by two types of nuclear receptors
      (TRs), TRalpha and TRbeta, which control target gene transcription. The relative
      contributions of the two TR products in mediating adult TH responses are poorly
      understood. As TRalpha1 transcripts are widely distributed in the brain, they
      presumably mediate most of the TH effects. This report examines the role and
      specific functions of T3 receptor isoforms on regulation of striatal synaptic
      plasticity indicators using adult hypothyroid mutant mice that fail to express
      single or multiple TR gene products. We then evaluated the effect of this
      hypothyroidism, with or without subsequent administration of T3, on T3 nuclear
      receptor (TRalpha1, TRbeta) and synaptic plasticity gene expression in
      TRalpha(0/0), TRbeta(-/-) and wild-type 129/SV mice. Hypothyroid wild-type mice
      exhibited reduced TRbeta, RC3, CaMKII and Rhes expression. The mRNA levels of
      Rhes and CaMKII were the same in all three hypothyroid substrains. By contrast,
      hypothyroid TRbeta(-/-) mice had higher RC3 mRNA levels than wild-type. T3
      administration restored TRbeta, RC3 and CaMKII levels in hypothyroid wild-type
      mice, without significant Rhes upregulation. T3 administration normalised
      expression of all genes studied in hypothyroid TRbeta(-/-) but not TRalpha(0/0)
      mice. Thus, TRalpha apparently plays an essential role in restoring the
      expression of the TH-regulated genes potentially involved in striatal synaptic
      plasticity.

PMID- 19094094
TI  - Expression of leptin receptor by glial cells of the nucleus tractus solitarius:
      possible involvement in energy homeostasis.
AB  - Leptin, an adipocyte-derived hormone, regulates food intake and body weight by
      acting principally on the hypothalamus, which displays the highest expression of
      leptin receptor (Ob-R). Nevertheless, other regions of the brain express Ob-R and
      constitute leptin's target sites. The dorsal vagal complex (DVC), an integrative
      centre of autonomic functions located in the caudal brainstem, is one of these
      structures. Leptin, by acting through the DVC, affects autonomic and
      neuroendocrine functions, such as control of food intake and gastric motility. In
      the present study, we observed Ob-R labelling within the DVC in cells that
      correspond to neuronal cell bodies. We showed for the first time Ob-R expression
      in a subpopulation of glial fibrillary acid protein positive cells located at the
      border between the area postrema and the nucleus tractus solitarius (NTS). These
      glial cells exhibit an atypical morphology consisting of unbranched processes
      that radiate rostro-caudally from the fourth ventricle wall. In vitro, the glial
      cells exhibited both long and short Ob-R expression with a preferential
      expression of the Ob-Ra and-f isoforms. Interestingly, using i.v and i.c.v.
      injection of the fluorescent tracer hydroxystilbamidine, we provided evidence
      that these cells may constitute a diffusion barrier which might regulate entry of
      molecules into the NTS. Finally, modulation of energy status, by acute or chronic
      reduction of food intake, modulated especially the short Ob-R isoforms in the
      DVC. In the light of these results, we hypothesise that Ob-R positive glial cells
      of the DVC participate in the transport of leptin into the brainstem and thus
      contribute to regulation of energy homeostasis.

PMID- 19094096
TI  - Progesterone attenuates oestrogen neuroprotection via downregulation of oestrogen
      receptor expression in cultured neurones.
AB  - Recent findings indicate that progesterone can attenuate the beneficial neural
      effects of oestrogen. In the present study, we investigated the hypothesis that
      progesterone can modulate oestrogen actions by regulating the expression and
      activity of oestrogen receptors, ERalpha and ERbeta. Our studies in cultured
      neurones demonstrate that progesterone decreases the expression of both ERalpha
      and ERbeta and, as a consequence, also reduces both ER-dependent transcriptional
      activity and neuroprotection. These results identify a potential mechanism by
      which progesterone antagonises neural oestrogen actions, a finding that may have
      important implications for hormone therapy in postmenopausal women.

PMID- 19094098
TI  - Nursing leadership development: why should any nurse be led by you?

PMID- 19094095
TI  - Relationship between social rank and cortisol and testosterone concentrations in
      male cynomolgus monkeys (Macaca fascicularis).
AB  - In nonhuman primate social groups, biological differences related to social
      status have proven useful for investigating the mechanisms of sensitivity to
      various disease states. Physiological and neurobiological differences between
      dominant and subordinate monkeys have been interpreted in the context of chronic
      social stress. The present experiments were designed to investigate the
      relationships between basal cortisol and testosterone concentrations and the
      establishment and maintenance of the social hierarchy in male cynomolgus monkeys.
      Cortisol concentrations were measured at baseline and following suppression with
      dexamethasone (DEX) and subsequent administration of adrenocorticotrophic hormone
      (ACTH) while monkeys were individually housed (n = 20) and after 3 months of
      social housing (n = 4/group), by which time dominance hierarchies had stabilised.
      Cortisol was also measured during the initial 3 days of social housing. Neither
      pre-social housing hormone concentrations, nor hypothalamic-pituitary-adrenal
      (HPA) axis sensitivity predicted eventual social rank. During initial social
      housing, cortisol concentrations were significantly higher in monkeys that
      eventually became subordinate; this effect dissipated within 3 days. During the
      12 weeks of social housing, aggressive and submissive behaviours were observed
      consistently, forming the basis for assignment of social ranks. At this time,
      basal testosterone and cortisol concentrations were significantly higher in
      dominant monkeys and, after DEX suppression, cortisol release in response to a
      challenge injection of ACTH was significantly greater in subordinates. These
      results indicate that basal cortisol and testosterone concentrations and HPA axis
      function are state variables that differentially reflect position in the
      dominance hierarchy, rather than trait variables that predict future social
      status.

PMID- 19094099
TI  - Nurse leaders and competition--are the blind leading the blind to market?
AB  - Marketisation of health care provision in the UK will result in a 'seismic'
      culture shift for many organizations and their nurse leaders. This short item
      explores the role nurse leaders will need to play in a world where increasingly,
      competition is becoming as important as collaboration.

PMID- 19094100
TI  - Patient centred leadership in practice.
AB  - AIM: To explore patient centred leadership at every level in an organisation and
      provide practical examples of how this was demonstrated in an acute tertiary NHS
      Trust. BACKGROUND: There is a direct relationship between leadership and quality
      of care. With increasing expansion of their role nurses are in a key position to
      influence and lead colleagues to improve patient care. EVALUATION: The Leadership
      Qualities Framework (NHS Institute of Innovation and Improvement 2006) is used to
      illustrate the various qualities used by clinical leaders in examples of
      leadership in practice. KEY ISSUE: Leadership development with the emphasis on
      the patient drives improvements in service delivery and patient safety.
      CONCLUSION: Patient centred leadership is demonstrated when there is support at
      the top of the organisation. Politically aware nurses make effective patient
      centred leaders. Leadership development programmes provide staff with
      opportunities to acquire essential skills and qualities in order to contribute to
      the vision of the organisation. IMPLICATIONS FOR NURSING MANAGEMENT: Managers
      should support staff and take risks in order to empower nurses to implement
      initiatives which improve patient care. A process of communication using a
      variety of tools can have a impact on a range of staff. Patient centred leaders
      are role models for tomorrow's leaders, their impact has lasting effect and wider
      implications within an organisation and beyond.

PMID- 19094101
TI  - Preparing nurse leaders for 2020.
AB  - AIM: This article highlights eight leadership competencies likely to be an
      essential part of the nurse leader's repertoire in 2020. BACKGROUND: Planning for
      the future is difficult, even when environments are relatively static. When
      environments are dynamic, the challenges multiply exponentially. Unfortunately,
      few environments have been more unpredictable in the 21st century than health
      care. The healthcare system is in chaos, as is much of the business world. It is
      critical then that contemporary nursing and healthcare leaders identify skill
      sets that will be needed by nurse leaders in 2020 and begin now to create the
      educational models and management development programs necessary to assure these
      skills are present. RESULTS: Essential nurse leader competencies for 2020
      include: (i) A global perspective or mindset regarding healthcare and
      professional nursing issues. (ii) Technology skills which facilitate mobility and
      portability of relationships, interactions, and operational processes. (iii)
      Expert decision-making skills rooted in empirical science. (iv) The ability to
      create organization cultures that permeate quality healthcare and patient/worker
      safety. (v) Understanding and appropriately intervening in political processes.
      (vi) Highly developed collaborative and team building skills. (vii) The ability
      to balance authenticity and performance expectations. (viii) Being able to
      envision and proactively adapt to a healthcare system characterized by rapid
      change and chaos. CONCLUSIONS: Nursing education programmes and healthcare
      organizations must be begin now to prepare nurses to be effective leaders in
      2020. This will require the formal education and training that are a part of most
      management development programmes as well as a development of appropriate
      attitudes through social learning. Proactive succession planning will also be key
      to having nurse leaders who can respond effectively to the new challenges and
      opportunities that will be presented to them in 2020.

PMID- 19094102
TI  - Key challenges facing American nurse leaders.
AB  - What are the key challenges facing nurse leaders in the United States? To find
      out, I asked 20 prominent nurse leaders to respond to that question and tell me
      their top three issues. Their voices tell a compelling story on challenges faced
      by the nurse leaders in American healthcare. The focus is no longer just on the
      process of how care is delivered, but on the outcomes of that care. More
      attention is being given to documenting that the care is provided according to
      specific standards associated with better outcomes. Many of the standards are
      directly related to the care given by nurses, including some indicators that are
      specifically sensitive to nurse intervention. There is also a new focus on
      federal reporting of patient satisfaction with the services provide. Producing
      quality outcomes, high patient satisfaction and effective measurements of both
      are now a central theme for the entire hospital administrative team. For the
      nurse leader, however, it represents explicit accountability for managing and
      leading the staff responsible for providing the patient care. Safety and quality
      issues are directly linked to financial pressure. Reimbursement for hospital is
      being whittled away as financial accountability for services receives greater
      scrutiny from the federal government and private insurers. Close on the heels of
      the financial challenge is the ever present workforce shortage. The most
      troublesome challenge identified by these nurse leaders is the absence of an
      adequate pipeline for nursing leaders. It is an exciting time for nursing in the
      United States. Challenges to be sure, but these nurse leaders have identified the
      priorities that will create a successful future.

PMID- 19094103
TI  - Nursing leaders of tomorrow: a peer selection process.
AB  - AIMS: This paper describes a case presentation of a process for using peer
      evaluation to identify and select new nursing leaders in hospital settings.
      BACKGROUND: A reliable method for identifying emerging leaders has yet to be
      defined. Often, it is based only on managerial observation and evaluation, and
      does not involve staff opinion. METHODS: We developed a three-tiered selection
      process consisting of: confidential peer voting, head nurse recommendations and a
      personal interview. RESULTS: Forty-three potential leaders were enrolled in our
      leadership training workshop. Twelve graduates of this workshop were chosen to
      fill leadership positions in the hospital. CONCLUSIONS: Peer recognition of
      potential nursing leaders might serve as a critical component in the process of
      selecting future nursing leaders. IMPLICATIONS FOR NURSING MANAGEMENT: Combining
      peer evaluation with structured leadership selection may be beneficial for the
      early recognition of future nursing leaders. This approach is not commonly used
      in the leader identification and selection process. It may contribute to a sense
      of trust between management and staff, and promote transparency as well as
      legitimacy in the selection process.

PMID- 19094104
TI  - Is there a relationship between personality type and preferred conflict-handling
      styles? An exploratory study of registered nurses in southern Mississippi.
AB  - AIM(S): The purpose of this study was to determine the relationship between
      different personality factors of female registered nurses and their method of
      dealing with conflict. BACKGROUND: Conflict is both necessary and absolute and
      factors that influence development and resolution of conflict include personality
      traits. METHODS: Ninety-seven female registered nurses working in three health
      care facilities in south Mississippi participated in this quantitative study.
      INSTRUMENTS: The instruments used were the Myers Briggs Type Indicator and the
      Thomas Kilmann Mode Instrument, which are forced choice questionnaires resulting
      in numerical data. RESULTS: There was not a statistically significant correlation
      between female registered nurses' personality factors and methods of dealing with
      conflict. CONCLUSIONS: The literature reveals that interpersonal conflict among
      nurses is a significant issue for the nursing profession. However, according to
      this study, there is no relationship between registered nurses' personality
      factors and methods used to deal with conflict. IMPLICATIONS FOR NURSING
      MANAGEMENT: The United States is faced with a serious nursing shortage, in part
      due to job dissatisfaction related to conflict in the workplace. Understanding
      conflict management styles can increase registered nurses' positive conflict
      outcomes and lead to improved relationships, increased job satisfaction, and
      increased retention of registered nurses.

PMID- 19094105
TI  - Registered Nurses' views on their professional role.
AB  - AIM: The aim is to study Registered Nurses' opinions and reflections about their
      work tasks, competence and organization in acute hospital care. BACKGROUND: The
      definition of the role of nurses has changed over time and it is often discussed
      whether Registered Nurses have a professional status or not. METHOD: A
      qualitative research design was used. Data were derived from written reflections
      on diaries and from focus group interviews. RESULTS: All respondents had
      difficulties in identifying the essence of their work. It can be argued that
      being 'a spider in the web' is an important aspect of the nursing profession.
      CONCLUSION: Registered Nurses tend to regard their professional role as vague.
      Managers must be considered key persons in defining the professional role of
      Registered Nurses. IMPLICATIONS FOR NURSING MANAGEMENT: This study contributes to
      an understanding of the managers' and the importance of nursing education in
      Registered Nurses professional development.

PMID- 19094106
TI  - 'How do we get the managers we need and the leaders we want?' A personal view.
AB  - For most patients and the general public, their most significant interface within
      the hospital setting occurs at the ward level. Here, the professional abilities
      of the Ward Sister/Charge Nurse--as well as the ward environment--will have a
      major impact on the experience and outcome of the patient's stay in hospital. It
      will also strongly influence the opinion of relatives and friends about the
      standards of care being delivered in that hospital. Ward managers are expected to
      demonstrate not only clinical leadership, but also be competent at dealing with
      the plethora of organisational issues which arise on their ward on a daily basis.
      As part of a professional response to the public's concerns around the
      environment of care within our hospitals and the perception that nursing
      leadership is not what it was, Welsh Assembly Government have launched a new
      strategy to re-empower Ward Sisters/Charge Nurses and develop and support the
      nurse managers/leaders of the future.

PMID- 19094107
TI  - Reflection: an educational strategy to develop emotionally-competent nurse
      leaders.
AB  - AIM: This paper explores educational strategies for nurses that focus on
      reflectivity and promote the development of self-awareness, relationship and
      communication skills and ability to lead with presence and compassion in the
      midst of change. BACKGROUND: Today nurses move rapidly from carefully-controlled
      educational experiences to a fast-paced clinical world of increasing patient
      complexity amid calls for improved quality of care. Making the transition to
      clinical competence and leadership in practice requires a strong sense of self
      and emotional intelligence. EVALUATION: Pedagogies that integrate theoretical and
      data-based textbook learning with experiential learning and reflection are a
      foundation for the development of emotionally- and intellectually-competent
      leaders and requires new ways of assessing learner outcomes. KEY ISSUES:
      Reflection is a key instructional strategy for preparing transformational nurse
      leaders for interdisciplinary settings where they lead patient care management.
      The remarkable global spread of reflection in nursing education, practice and
      research follows an emphasis on developing self-awareness as a leadership
      strategy for improving individual and organizational performance. CONCLUSIONS:
      Empirical, experiential and anecdotal evidence suggests that reflection has the
      potential to prepare emotionally-capable nurse leaders. IMPLICATIONS FOR NURSING
      MANAGEMENT: As educators create more reflective and nurturing learning
      environments, they will promote the development of emotionally-competent nurse
      leaders who will, in turn, inspire individual and organizational growth and
      positive change in society.

PMID- 19094108
TI  - Promoting leadership: the development of a nurse executive team in an acute
      hospital trust.
AB  - AIM: The purpose of this study was to evaluate how an executive nursing team,
      within an acute hospital trust in the south of England, developed their
      leadership characteristics through the use of a professional development
      programme. BACKGROUND: This paper offers an insight into how this team worked
      together to clarify their views of their new role and how the role would be
      enacted. METHOD: A questionnaire using quantitative and qualitative measures was
      used to explore the group's leadership style and evaluate the professional
      development programme. FINDINGS: The findings show how the development programme
      worked and what clarity it afforded the group in terms of their leadership style.
      Group work, building on the findings, helped them define their particular
      characteristics, skills and leadership ability and what further work was needed
      to demonstrate this. CONCLUSIONS: The issues raised, such as team-working, mutual
      purpose and personal development, are discussed in terms of their function within
      an integrated executive team with vision and goals. IMPLICATIONS FOR NURSING
      MANAGEMENT: In ensuring that the nursing service has positive purpose, direction
      and goals, there needs to be a strategic approach to corporate development;
      otherwise, nursing will struggle to lead itself within a fast changing health
      care system.

PMID- 19094109
TI  - The impact of emotional intelligent leadership on staff nurse empowerment: the
      moderating effect of span of control.
AB  - AIM: To test a model linking nurses' perceptions of their nurse manager's
      emotionally intelligent leadership style and nurses' structural empowerment, and
      the impact of nurse manager span of control (number of direct reports) on the
      emotional intelligence/empowerment relationship. BACKGROUND: Hospital
      restructuring in the 1990s resulted in a dramatic reduction in nurse manager
      positions, yet nurse managers are critical to empowering nurses for professional
      practice. METHOD(S): A descriptive correlational survey design was used to test
      the hypothesized model in two community hospitals in Ontario. Two hundred and
      three nurses from two hospitals returned useable questionnaires (68% response
      rate). RESULTS: Span of control was a significant moderator of the relationship
      between nurses perceptions of their managers' emotionally intelligent behaviour
      and feelings of workplace empowerment. CONCLUSION: The results suggest that even
      managers with strong emotional intelligence may not be able to empower their
      staff if their span of control is large. IMPLICATIONS FOR NURSING MANAGEMENT:
      Every effort must be made to ensure that managers have reasonable spans of
      control that allow them to develop and use the leadership skill necessary for
      empowering their staff to practice to the full scope of their professional role.

PMID- 19094110
TI  - The relationship between emotional intelligence competencies and preferred
      conflict-handling styles.
AB  - AIMS: The purpose of this study was to determine if a relationship exists between
      emotional intelligence (EI) and preferred conflict-handling styles of registered
      nurses. BACKGROUND: Conflict cannot be eliminated from the workplace therefore
      learning appropriate conflict-handling skills is important. METHODS: Ninety-four
      registered nurses working in three south Mississippi healthcare facilities
      participated in this quantitative study. Ninety-two valid sets of data
      instruments were collected for this study. RESULTS: Higher levels of EI
      positively correlated with collaborating and negatively with accommodating.
      CONCLUSIONS: The issue of occupational stress and conflict among nurses is a
      major concern. It is imperative nurses learn how to effectively handle conflict
      in the work environment. Developing the competencies of EI and understanding how
      to effectively handle conflict is necessary for nurses working in a highly
      stressful occupation. IMPLICATIONS FOR NURSING MANAGEMENT: Effective leadership
      management includes conflict management and collaboration. The art of
      relationship management is necessary when handling other people's emotions. When
      conflict is approached with high levels of EI, it creates an opportunity for
      learning effective interpersonal skills. Understanding how EI levels and conflict
      skills correlate can be used to improve interpersonal relationships in a
      healthcare facility.

PMID- 19094111
TI  - Attaining organizational commitment across different generations of nurses.
AB  - AIM: To inform nurse managers about the generational differences that exist among
      nurses, how it affects the work environment and how this information can be used
      to encourage organizational commitment. BACKGROUND: Every person is born into a
      generational cohort of peers who experience similar life experiences that go on
      to shape distinct generational characteristics. Thanks to delayed retirements,
      mid-life career changes, job re-entry and a small but significant group of
      younger graduates, the nursing profession is now experiencing four generations in
      the workforce: Veterans, Baby Boomers, Generation X and the Millennial
      Generation. At the same time, the literature on organizational commitment is
      expanding and can provide a compelling context through which to view generational
      differences among nurses. IMPLICATIONS FOR NURSING MANAGEMENT: As part of an
      overall strategy to increase organizational commitment, consideration of
      generational differences in nurses can be helpful in leading to increased job
      satisfaction, increased productivity and decreased turnover among staff. In the
      face of the global nursing shortage, managers should increase their knowledge of
      generational diversity just as they have with ethnic and cultural diversity in
      the past. Understanding how to relate to the different generations and tap into
      their individual strengths can lead to improved nursing work environments.

PMID- 19094112
TI  - The 'F.E.E.L.' good factors in nursing leadership at board level through work
      based learning.
AB  - AIM: The aim of this commentary is to raise awareness about the apparent lack of
      formal activities and the paucity of published papers in nursing leadership
      development at the board level in the United Kingdom (UK). The paper suggests a
      way forward. BACKGROUND: The author has been serving at a board level, within and
      outside of nursing, locally, nationally and internationally since 1988. His
      current experience as an active board member and honorary treasurer of a leading
      charity organization in the Southeast of England and participation on a Board
      Leadership Development programme in the United States of America (USA) led to the
      need to write this commentary. EVALUATION: Leadership at the board level is
      different because the board is the governing body of an organization. The board
      has overall responsibility for running the organization. The overall duty is to
      manage less and LEAD more. The need for this type of leadership is on the
      increase because these are turbulent days in the healthcare industry. This
      growing trend witnesses increasing and greater demand from key stakeholders for
      nursing and healthcare services: rising exposure to liability and litigation; a
      demand for stronger accountability and questioning of the nature and delivery of
      nursing and healthcare services. Effective and successful leadership judgment is
      made based on both numbers [efficient resources utilization (RU)] and stories
      [effective client/patient satisfaction (CS)]. CONCLUSIONS: Nurses and others in
      the healthcare industry need to guide against the leadership myths that:
      'everyone can be a leader'; 'leaders deliver business (service) results'; 'people
      who get to the top are leaders'; and 'that leaders are great coaches'. This
      commentary demonstrates these myths could be converted to become realities
      through developing and possessing most if not all the knowledge, skills and
      attitudes implicated in the Effective Board Leadership Capabilities Development
      Profile presented in this paper. IMPLICATIONS FOR NURSING MANAGEMENT AND
      LEADERSHIP: Possessing board level leadership capabilities is significant to
      nursing management and leadership from three key perspectives: the need for
      nurses to become 'recognized' leaders of the healthcare industry; possessing the
      knowledge, skills and attitudes relevant for effective board leadership; and the
      need to use the technology of the 21st century to aspire to an essentially
      intentionally global nursing community.

PMID- 19094114
TI  - Magnet hospital characteristics in acute general hospitals in Ireland.
AB  - AIM: The aim of this research was to investigate characteristics of the nursing
      practice environment and the impact of organizational structures and processes on
      nursing in 11 major acute general hospitals in Ireland from the perspective of
      staff-nurses (n = 368) and Directors of Nursing (n = 10). METHODS: The study was
      descriptive, cross-sectional and quantitative. The Nursing Work Index-Revised
      (NWI-R) and an instrument developed by Havens were used and Directors of Nursing
      supplied hospital documentary evidence of organizational structures and
      processes. A convenience sample of 368 staff-nurses and 10 Directors of Nursing,
      participated. RESULTS: Staff-nurses had a moderately positive perception of
      relationships with doctors (2.77); autonomy in practice (2.56); organizational
      support (2.51) and control over practice settings (2.35). A significant
      statistical difference was found between the practice environments in the 11
      hospitals, particularly in relation to organizational support (P = 0.001);
      control over practice setting (P = 0.003); nurse autonomy (P = 0.004) and nurse
      doctor relationships (P = 0.024). CONCLUSION: When comparisons were made with US
      Magnet hospital research findings, lower scores on all dimensions of professional
      practice environment were achieved by Irish nurses.

PMID- 19094115
TI  - The roles of the first-line nurse manager: perceptions from four perspectives.
AB  - AIM: To study the perception of the first-line nurse managers (FLNMs), registered
      nurses (RNs), assistant nurses (ANs) and head of departments (HDs) on the FLNM's
      current and desired roles. BACKGROUND: In the process of decentralization, the
      role of FLNM has changed from having overall responsibility for patients to
      having responsibility for the management of the ward. METHOD: Interviews with
      five FLNMs, five RNs, five ANs, and one HD were used. Qualitative content
      analysis was used to analyse the transcribed text. RESULTS: When describing the
      current roles, the FLNMs, RNs and ANs focused on the coordination of activities
      that contributed to a well-functioning service and care of patients as well as on
      the recruitment of, support to and development of the personnel. The HD focused
      on the FLNM's responsibilities towards the personnel, especially regarding
      empowerment and staff well-being. When describing desired roles, the FLNMs, RNs
      and ANs emphasized service on the ward while the HD underlined the development of
      services and co-operation with other nurse managers. CONCLUSION: The perception
      of the current and desired roles of the FLNM varied among the groups. The FLNMs,
      RNs and ANs reported a similar understanding which in turn differed from that of
      the HD who described fewer roles and focused on other areas.

PMID- 19094116
TI  - Toll-like receptor-induced granulocyte-macrophage colony-stimulating factor
      secretion is impaired in Crohn's disease by nucleotide oligomerization domain 2
      dependent and -independent pathways.
AB  - Pattern recognition receptors (PRRs) are an integral part of the innate immune
      system and govern the early control of foreign microorganisms. Single nucleotide
      polymorphisms (SNPs) in the intracellular pattern recognition receptor nucleotide
      binding oligomerization domain-containing protein (NOD2, nucleotide
      oligomerization domain 2) are associated with Crohn's disease (CD). We
      investigated the impact of NOD2 polymorphisms on cytokine secretion and
      proliferation of peripheral blood mononuclear cells (PBMCs) in response to Toll
      like receptor (TLR) and NOD2 ligands. Based on NOD2 SNP analyses, 41 CD patients
      and 12 healthy controls were studied. PBMCs were stimulated with NOD2 and TLR
      ligands. After 18 h culture supernatants were measured using multiplex assays for
      the presence of human cytokines granulocyte-macrophage colony-stimulating factor
      (GM-CSF), interleukin (IL)-1 beta and tumour necrosis factor (TNF)-alpha. In CD
      patients, TLR-induced GM-CSF secretion was impaired by both NOD2-dependent and 
      independent mechanisms. Moreover, TNF-alpha production was induced by a TLR-2
      ligand, but a down-regulatory function by the NOD2 ligand, muramyl dipeptide, was
      impaired significantly in CD patients. Intracellular TLR ligands had minimal
      effect on GM-CSF, TNF-alpha and IL-1beta secretion. CD patients with NOD2
      mutations were able to secrete TNF-alpha, but not GM-CSF, upon stimulation with
      NOD2 and TLR-7 ligands. CD patients have impaired GM-CSF secretion via NOD2
      dependent and -independent pathways and display an impaired NOD2-dependent down
      regulation of TNF-alpha secretion. The defect in GM-CSF secretion suggests a
      hitherto unknown role of NOD2 in the pathogenesis of CD and is consistent with
      the hypothesis that impaired GM-CSF secretion in part constitutes a NOD2
      dependent disease risk factor.

PMID- 19094117
TI  - Induction of autoimmune cholangitis in non-obese diabetic (NOD).1101 mice
      following a chemical xenobiotic immunization.
AB  - Our laboratory has suggested that loss of tolerance to pyruvate dehydrogenase
      (PDC-E2) leads to an anti-mitochondrial antibody response and autoimmune
      cholangitis, similar to human primary biliary cirrhosis (PBC). We have suggested
      that this loss of tolerance can be induced either via chemical xenobiotic
      immunization or exposure to select bacteria. Our work has also highlighted the
      importance of genetic susceptibility. Using the non-obese diabetic (NOD) congenic
      strain 1101 (hereafter referred to as NOD.1101 mice), which has chromosome 3
      regions from B6 introgressed onto a NOD background, we exposed animals to 2
      octynoic acid (2OA) coupled to bovine serum albumin (BSA). 2OA has been
      demonstrated previously by a quantitative structural activity relationship to
      react as well as or better than lipoic acid to anti-mitochondrial antibodies. We
      demonstrate herein that NOD.1101 mice immunized with 2OA-BSA, but not with BSA
      alone, develop high titre anti-mitochondrial antibodies and histological
      features, including portal infiltrates enriched in CD8(+) cells and liver
      granulomas, similar to human PBC. We believe this model will allow the rigorous
      dissection of early immunogenetic cause of biliary damage.

PMID- 19094119
TI  - Localized erosive pustular dermatosis of the scalp at the site of a cochlear
      implant: successful treatment with topical tacrolimus.
AB  - Erosive pustular dermatosis of the scalp (EPDS) is a rare form of nonmicrobial
      pustulosis mainly occurring in elderly patients with long-term sun damage to the
      skin. Clinically, it is characterized by pustular lesions that progressively
      merge into erosive and crusted areas over the scalp. The histology of EPDS is
      nonspecific, and its pathophysiology remains undetermined, with various types of
      local trauma possibly acting as the triggering factor. We describe a 24-year-old
      woman who developed EPDS after cochlear implant surgery for profound
      sensorineural hearing loss. We speculate that either the cutaneous surgery during
      cochlear implantation or the skin inflammation that commonly occurs near the
      magnet might have triggered the disorder. It is of note that the patient's skin
      lesions healed completely after treatment with topical tacrolimus, a relatively
      novel immunosuppressive molecule. Thus, topical tacrolimus may be indicated as a
      therapeutic alternative to the widely used steroids for this disease, mainly to
      avoid steroid-related cutaneous atrophy.

PMID- 19094118
TI  - Successful granulocyte-colony stimulating factor treatment of Crohn's disease is
      associated with the appearance of circulating interleukin-10-producing T cells
      and increased lamina propria plasmacytoid dendritic cells.
AB  - Granulocyte-colony stimulating factor (G-CSF) has proved to be a successful
      therapy for some patients with Crohn's disease. Given the known ability of G-CSF
      to exert anti-T helper 1 effects and to induce interleukin (IL)-10-secreting
      regulatory T cells, we studied whether clinical benefit from G-CSF therapy in
      active Crohn's disease was associated with decreased inflammatory cytokine
      production and/or increased regulatory responses. Crohn's patients were treated
      with G-CSF (5 microg/kg/day subcutaneously) for 4 weeks and changes in cell
      phenotype, cytokine production and dendritic cell subsets were measured in the
      peripheral blood and colonic mucosal biopsies using flow cytometry, enzyme-linked
      immunosorbent assay and immunocytochemistry. Crohn's patients who achieved a
      clinical response or remission based on the decrease in the Crohn's disease
      activity index differed from non-responding patients in several important ways:
      at the end of treatment, responding patients had significantly more CD4(+) memory
      T cells producing IL-10 in the peripheral blood; they also had a greatly enhanced
      CD123(+) plasmacytoid dendritic cell infiltration of the lamina propria.
      Interferon-gamma production capacity was not changed significantly except in non
      responders, where it increased. These data show that clinical benefit from G-CSF
      treatment in Crohn's disease is accompanied by significant induction of IL-10
      secreting T cells as well as increases in plasmacytoid dendritic cells in the
      lamina propria of the inflamed gut mucosa.

PMID- 19094120
TI  - Asymmetrical periflexural exanthem exhibiting pseudoisomorphic Koebner response
      in an adult.
AB  - Asymmetrical periflexural exanthem is a rare clinical condition, seen almost
      exclusively in children. Very few adult cases have been reported in the
      literature. We report a case of this rare eruption in an adult man showing
      characteristic clinical and histological features. Interestingly, this patient
      also exhibited a pseudoisomorphic Koebner response. Although an infective
      aetiology of viral origin has been suggested for this localized eruption, the
      aetiology remains unknown. We are of the opinion that the pseudoisomorphic
      Koebner response in this patient may support the inoculation hypothesis in the
      pathogenesis of this disorder.

PMID- 19094121
TI  - Acute scurvy during treatment with interleukin-2.
AB  - The association of vitamin C deficiency with nutritional factors is commonly
      recognized. However, an acute form of scurvy can occur in patients with an acute
      systemic inflammatory response, which is produced by sepsis, medications, cancer
      or acute inflammation. The frequency of acute hypovitaminosis C in hospitalized
      patients is higher than previously recognized. We report the occurrence of acute
      signs and symptoms of scurvy (perifollicular petechiae, erythema, gingivitis and
      bleeding) in a patient hospitalized for treatment of metastatic renal-cell
      carcinoma with high-dose interleukin-2. Concomitantly, serum vitamin C levels
      decreased to below normal. Better diets and longer lifespan may result a lower
      frequency of acute scurvy and a higher frequency of scurvy associated with
      systemic inflammatory responses. Therefore, increased awareness of this condition
      can lead to early recognition of the cutaneous signs of acute scurvy in
      hospitalized patients with acute illnesses or in receipt of biological agents,
      and prevent subsequent morbidity such as bleeding, anaemia, impaired immune
      defences, oedema or neurological symptoms.

PMID- 19094122
TI  - Juvenile folliculotropic and ichthyosiform mycosis fungoides.
AB  - Ichthyosiform mycosis fungoides (MF) is a recently recognized clinical variant of
      MF, which appears as dry scaling patches and plaques, or as a generalized
      eruption. Acquired ichthyosis is well recognized as a paraneoplastic cutaneous
      presentation of malignancy, especially in lymphoproliferative disorders. In
      contrast, the ichthyosiform eruption in ichthyotic MF is attributable to
      infiltration of the skin by tumour cells. We report the case of a 15-year-old boy
      who presented with a 5-year history of enlarging pruritic plaques on the forehead
      and back, patchy alopecia and generalized ichthyosis. Histology of the forehead
      and back showed a dense, lymphocytic, folliculocentric and perivascular
      infiltrate of predominantly CD4-positive T cells consistent with folliculotropic
      MF. Histological examination of biopsies from ichthyotic skin found similar
      features. Our patient had a histological diagnosis at the age of 15 years, making
      him the youngest reported patient with either folliculotropic MF or ichthyotic
      MF.

PMID- 19094124
TI  - Purpura and bleeding due to calcium-channel blockers: an underestimated problem?
      Case reports and a pilot study.
AB  - BACKGROUND: Surgical bleeding and occasionally purpura due to calcium-channel
      blockers have been described. AIM: To present cases in whom purpura or internal
      bleeding due to calcium-channel blockers was a presenting feature, including one
      subject with drug-induced haematuria and haematospermia due to amlodipine and one
      with the Rumpel-Leede sign. Further support for a true association was sought in
      a pilot study using Hess testing to provoke purpuric skin lesions. METHODS: Four
      representative cases presenting due to purpura or bleeding are described, all of
      whom had an abnormal Hess test. A further 19 patients taking calcium-channel
      blockers and 13 control subjects were also tested. RESULTS: Of 19 patients on
      calcium-channel blockers, 16 had either abnormal Hess results (n = 13) or marked
      acral purpura (n = 3) after a Hess test procedure. A similar abnormal response,
      of milder degree, occurred in only 2 of 13 control subjects. CONCLUSIONS: The
      high frequency of purpura shown in this study, whether spontaneous or provoked,
      suggests that this is a pharmacological class effect rather than idiosyncratic.
      Purpura in patients taking these drugs may be a clue to diagnosis of internal or
      postsurgical bleeding. We conclude that purpura related to calcium-channel
      antagonists is probably underestimated, but further studies are needed to
      identify the mechanism by which this occurs.

PMID- 19094123
TI  - Postoperative pyoderma gangrenosum: diagnostic value of 16s ribosomal RNA
      sequencing and review of the literature.
AB  - BACKGROUND: Pyoderma gangrenosum (PG) is an uncommon condition, but can lead to
      the diagnosis of an underlying systemic disease. It can appear spontaneously or
      as a result of the pathergy phenomenon after trauma or surgery. METHODS: We
      review three patients with postoperative PG (PPG) and the relevant literature. We
      also report an accurate method for microbial detection by 16S ribosomal (r)RNA
      sequencing. RESULTS: A 47-year-old woman and two men aged 54 and 48 years,
      respectively, presented with sterile ulcerations after surgery. Associated
      conditions (Crohn's disease and leukaemia) were present. Surgical wound infection
      was suspected and systemic empirical antibiotics were prescribed. After infection
      was excluded, PPG was diagnosed and corticosteroids were started. DISCUSSION: PPG
      should be considered in the differential diagnosis of postsurgical wound
      complications. Recognition of this condition may prevent unnecessary
      administration of antimicrobial treatment and development of more extensive
      ulcerations. It may also be the clue for the diagnosis of an underlying systemic
      disease. We discuss the usefulness of 16S rRNA sequencing for microbial detection
      and identification in order to exclude a causative infection in patients who have
      previously received antibiotic treatment.

PMID- 19094125
TI  - Urticaria pigmentosa associated with acute stress and lesional skin mast-cell
      expression of CRF-R1.
AB  - A 38-year-old woman presented with a pronounced increase in symptoms and
      proliferation of urticaria pigmentosa (UP) after acute psychological stress,
      which was quantified using the Spielberger's State-Trait Anxiety Inventory.
      Immunohistochemical examination of a skin biopsy from a new UP lesion showed a
      large number of activated mast cells expressing corticotrophin-releasing factor
      receptor-1 (CRF-R1) and there was high serum CRF. This is the first documented
      report to our knowledge of UP worsening associated with acute stress, possibly
      through activation of skin mast-cell CRF-R1.

PMID- 19094126
TI  - Lupus vulgaris at the site of BCG vaccination: report of three cases.
AB  - Lupus vulgaris (LV) is a rare complication of the bacille Calmette-Guerin (BCG)
      vaccination, and about 65 cases of inoculation tuberculosis resembling LV have
      been reported in the literature. We report three cases of LV, developing many
      years later at the inoculation site of BCG vaccine. All three cases had a single
      BCG vaccination, with a LV lesion at or in the vicinity of the vaccination site,
      a strong positive Mantoux test, noncaseating granuloma histologically, and two of
      the patients had a positive PCR result for mycobacterial complex. One of the
      patients had an unusually delayed appearance of the LV lesion, after an interval
      of about 17 years, and another case was remarkable because of the large size of
      the lesion (210 x 110 mm).

PMID- 19094127
TI  - Clinical and histopathological characteristics of pityriasis alba.
AB  - BACKGROUND: Pityriasis alba (PA) is a skin disorder characterized by
      asymptomatic, variably hypopigmented, slightly scaling patches with indistinct
      margins. It is sometimes difficult to clinically differentiate PA from other
      hypopigmented disorders such as naevus depigmentosus. AIM: To examine the
      clinical and histopathological characteristics of PA that are important in
      differentiating PA from other hypopigmenting disorders. METHODS: A clinical
      survey was carried out on 56 patients with PA. Histopathological features were
      investigated with immunostains for NKI/beteb antibody, melanoma antigen
      recognized by T cells (MART)-1 and S-100 protein, and by haematoxylin and eosin
      and Fontana-Masson stains. RESULTS: Of the 56 PA patients, 10 (18%) had a
      previous history of atopic dermatitis and 9 (16%) had a solitary lesion.
      Histopathological study revealed markedly reduced pigment in the epidermis of
      lesional skin, but no significant difference in melanocyte count was found
      between lesional and normal skin. Ultrastructurally, degenerative changes in
      melanocytes and a reduced number of melanosomes within keratinocytes were seen.
      CONCLUSION: No significant difference in the number of melanocytes between
      lesional and normal skin was seen. These findings should be considered when
      diagnosing and differentiating PA from other hypopigmentary disorders.

PMID- 19094128
TI  - Malformations of the index nails.
AB  - We report a 52-year-old woman with micronychia of the index fingers. Radiographic
      examination revealed a Y-shaped bifurcation of the distal phalanx of both index
      fingers. She was diagnosed with congenital onychodysplasia of the index fingers
      (COIF) or Iso-Kikuchi syndrome. COIF is a rare condition characterized by a
      variety of nail dysplasia of the index fingers. Five criteria characterize COIF:
      congenital occurrence, unilateral or bilateral index finger involvement,
      variability in nail appearance, hereditary involvement and frequently associated
      bone abnormalities. Micronychia, polyonychia, anonychia, hemionychrogryphosis and
      malalignment are the observed index finger defects. Most cases have been
      described in Japan, and to our knowledge, this is the first case of COIF reported
      in South America.

PMID- 19094129
TI  - Cutaneous granular bacteriosis, a rarely diagnosed infection of the head and the
      neck.
AB  - A young man presented with a large multilobulated and mutilating tumour of the
      scalp, which had been relapsing for years. Histological examination of a biopsy
      from the lesion revealed chronic inflammation with granulation tissue and
      presence of granules with eosinophilic periphery, which was positive for Gram,
      Grocott and periodic-acid-Schiff stains. A large excision was performed. Cultures
      grew Staphylococcus aureus. The patient was treated with penicillin G, but 4
      weeks after the start of treatment, new small nodules appeared over the same
      area. All these new nodules disappeared within 2 weeks the addition of
      clindamycin and cotrimoxazole. This triple antibiotic treatment was carried on
      for 18 months, and the patient remained disease-free after a follow-up of 4
      years. Although the lesions were clinically and histologically suggestive of
      actinomycosis, culture revealed that they were caused by a completely different
      organism. We suggest grouping such lesions under a single term "granular
      bacteriosis" and combining surgery with broad-spectrum antibiotics covering
      Actinomyces species and botryomycosis-causing organisms (mainly Staphylococcus).

PMID- 19094130
TI  - Intravenous immunoglobulin treatment in laryngeal pemphigoid.
AB  - We report a 29-year-old white woman who presented with oral involvement and
      subsequently developed severe and extensive laryngeal involvement with mucous
      membrane pemphigoid. She could not tolerate systemic corticosteroids due to side
      effects. Dapsone improved only the oral disease, but the laryngeal disease
      remained active and progressive. She refused immunosuppressive agents, because
      she wanted to conceive. The acute severe widespread laryngeal pemphigoid was
      accompanied by severe relentless coughing and dysphonia. The patient was treated
      with intravenous immunoglobulin (IVIg) as monotherapy, which led to complete
      resolution of the symptoms and the laryngeal lesions, as seen on repeated direct
      laryngoscopies. The normal anatomy and function of the larynx was restored, and
      scarring did not occur. The patient did not develop any side-effects to the IVIg
      treatment, which led to disease remission. While on IVIg treatment, she delivered
      a healthy child. She remained in remission after 5 years of follow-up.

PMID- 19094131
TI  - Reactivity to autologous serum skin test and relationship with complement levels
      in chronic idiopathic urticaria and angio-oedema.
AB  - BACKGROUND: A role for complement in autoantibody-mediated histamine release in
      urticaria has been suggested but not proven in vivo. Aim. To study serum
      complement levels in patients with chronic idiopathic urticaria (CIU) and to
      determine whether there was a relationship with autologous serum skin test (ASST)
      reactivity. METHODS: We recruited 35 patients with CIU. Complement (C3, C4)
      levels and ASST were measured in all patients; additional investigations were
      undertaken dependent on history and examination. RESULTS: Complement
      concentrations were outside the population reference intervals in 19/35 patients,
      with low C3 noted in 3/35 and low C4 in 18/35. Of 12 patients with a positive
      ASST, 7 had low complement levels, and 12/23 with a negative ASST had low
      complement levels. Patients with a positive ASST had a median C3 of 1.24 g/L
      (range 0.35-1.51) compared with a median of 1.25 g/L in those with a negative
      ASST (P = 0.36), and a median C4 of 0.20 g/L (range 0.185-0.452) in those with a
      positive ASST compared with 0.18 g/L in those with a negative ASST (P = 0.88).
      CONCLUSIONS: We conclude that both a reduction in C4 and positive ASST are common
      in CIU and although these immunological abnormalities often coexist, there is no
      clear relationship between them. Other components of the complement system may be
      worth exploring.

PMID- 19094132
TI  - Serum levels of transforming growth factor-beta1 in patients with mild psoriasis
      vulgaris and effect of treatment with biological drugs.
AB  - BACKGROUND: Psoriasis is an immune cell-mediated disease in which cytokines play
      an important role. Studies have been performed to explore the relationship
      between the disease and cytokine blood levels with a view to finding a biomarker
      for monitoring disease severity/activity and treatment efficacy. AIM: To
      investigate the levels of transforming growth factor-beta1 (TGF-beta1) in
      patients with mild psoriasis vulgaris (PV) and the possible use of this cytokine
      in monitoring treatment with biological drugs. METHODS: Serum levels of TGF-beta1
      were estimated in 33 untreated patients (PI group), in 7 of these patients (PII
      group) before and after 3 months of treatment with one of two biological drugs
      (etanercept and efalizumab) and in 19 healthy volunteers (control group).
      RESULTS: Significantly (P < 0.0001) higher serum levels of TGF-beta1 were found
      in the PI group [Psoriasis Area and Severity Index (PASI) 9-10] compared with the
      19 healthy volunteers. In the PII group, after the administration of one of the
      biological drugs, a 50% reduction in PASI and a significant (P = 0.032) decrease
      in TGF-beta1 was noted. CONCLUSIONS: Raised TGF-beta1 levels in patients with
      mild PV decreased in tandem with a decrease in PASI after biological drug
      treatment. Hence, TGF-beta1 levels seem to be sensitive to changes in disease
      severity.

PMID- 19094133
TI  - Two cases of factitial panniculitis induced by electroacupuncture.
AB  - Factitial panniculitis can be produced by mechanical, physical, or chemical
      means. It often causes an unusual clinical and histological feature that defies
      diagnosis until self-inoculation or mechanical trauma is suspected and proved.
      Acupuncture has been used in East Asia for centuries as a method of treatment for
      various conditions, especially for pain relief, and is known to be a relatively
      safe system. The needles are often manipulated by hand once they are placed at
      the acupuncture points. Electroacupuncture, the application of pulsating
      electrical current to acupuncture needles, was developed in China as an extension
      of hand manipulation, and produces continuous and stronger stimulation; however,
      although this may provide more effective treatment, it may also provoke more
      mechanical trauma. We report two cases of factitial panniculitis in two young
      women, who presented with multiple subcutaneous nodules along the
      electroacupuncture sites.

PMID- 19094134
TI  - Multiple cutaneous metastases from hilar cholangiocarcinoma.
AB  - The most common metastatic sites of cholangiocarcinoma are the retroperitoneal
      lymph nodes, peritoneum, liver and lungs, and cutaneous metastases of
      cholangiocarcinoma are rare. Although cutaneous metastases of internal
      malignancies most commonly present clinically as nontender nodules appearing in a
      particular area of body, other presentations can occur. Cutaneous metastases of
      cholangiocarcinoma can appear as a solitary tumour at the therapeutic drainage
      site. We report a 60-year-old man with unusual cutaneous metastases from hilar
      cholangiocarcinoma, which presented as multiple indurated plaques and papules on
      the anterior chest.

PMID- 19094135
TI  - Superimposed linear psoriasis: differential therapeutic response of linear and
      nonlinear lesions.
AB  - Linear psoriasis is a very unusual clinical variation of psoriasis. Typical
      clinical features include early onset of erythematosquamous lesions along
      Blaschko's lines, ability to elicit psoriatic features, absence of pruritus and
      positive family history for psoriasis. Recently, the term 'superimposed linear
      psoriasis' was coined for cases with development of nonlinear psoriatic lesions
      at predilection sites in later life. We report a 19-year-old woman meeting all
      criteria for the diagnosis of superimposed linear psoriasis including typical
      histological features. Remarkably, treatment with topical steroids and dithranol
      cleared the psoriatic lesions on predilection sites whereas the linear lesions
      were resistant to topical therapy. Linear psoriatic lesions are believed to be
      caused by genetic alterations in early embryogenesis leading to loss of
      heterozygosity at a gene locus involved in the pathogenesis of psoriasis.
      Comparison of mosaic keratinocytes derived from linear lesions with wild-type
      keratinocytes from the same person may therefore allow identification of key
      regulatory genes.

PMID- 19094136
TI  - Ecthyma gangrenosum: an important feature of pseudomonal sepsis in a previously
      well child.
AB  - Ecthyma gangrenosum is a rare, distinctive skin disorder associated with
      potentially fatal underlying pseudomonal sepsis. Although typically occurring in
      neutropenic or immunocompromised patients, it can occasionally affect healthy
      children. The appearances are characteristic with small indurated vesicular
      papules progressing rapidly to infarcted necrotic areas with surrounding erythema
      and a typical black eschar. In young children, these are often accompanied by
      fever and diarrhoea. The absence of suppuration and slough distinguishes it from
      the more recognized pyoderma gangrenosum. Lesions can occur at any site although
      are most commonly found over the buttocks, limbs, axillae and perineum. We
      describe the case of a 28-month-old, previously well child who presented with
      typical features of ecthyma gangrenosum secondary to Pseudomonas infection who
      responded to appropriate antibiotic treatment. Despite a thorough search, no
      underlying cause was found. Early recognition and prompt treatment with
      antipseudomonal antibiotics is vital to reduce morbidity and potential mortality.

PMID- 19094137
TI  - Superficial granulomatous pyoderma treated preoperatively with infliximab.
AB  - We report a case of superficial granulomatous pyoderma (SGP) treated successfully
      with infliximab. A 71-year-old woman developed erythema, erosions and cribriform
      scarring in the right periorbital area following enucleation of the right eye.
      Histology showed three-layered granulomas typical of SGP. The patient's disease
      was unusual in that it failed to respond to a wide variety of immunosuppressants
      and this condition is rarely reported to affect the face. Eventually she was
      treated successfully with infliximab, enabling her to undergo extensive surgery
      despite the fact that her disease was pathergic in onset.

PMID- 19094139
TI  - A nursing-specific model of EPR documentation: organizational and professional
      requirements.

PMID- 19094141
TI  - Clarification to article entitled "global nurse migration today".

PMID- 19094142
TI  - Logsdon acknowledges co-author's contribution.

PMID- 19094144
TI  - Nursing implementation science: how evidence-based nursing requires evidence
      based implementation.
AB  - PURPOSE: Evidence is not always used in practice, and many examples of
      problematic implementation of research into practice exist. The aim of this paper
      is to provide an introduction and overview of current developments in
      implementation science and to apply these to nursing. METHODS: We discuss a
      framework for implementation, describe common implementation determinants, and
      provide a rationale for choosing implementation strategies using the available
      evidence from nursing research and general health services research. FINDINGS:
      Common determinants for implementation relate to knowledge, cognitions,
      attitudes, routines, social influence, organization, and resources. Determinants
      are often specific for innovation, context, and target groups. Strategies focused
      on individual professionals and voluntary approaches currently dominate
      implementation research. Strategies such as reminders, decision support, use of
      information and communication technology (ICT), rewards, and combined strategies
      are often effective in encouraging implementation of evidence and innovations.
      Linking determinants to theory-based strategies, however, can facilitate optimal
      implementation plans. CONCLUSIONS: An analytical, deliberate process of
      clarifying implementation determinants and choosing strategies is needed to
      improve situations where suboptimal care exists. Use of theory and evidence from
      implementation science can facilitate evidence-based implementation. More
      research, especially in the area of nursing, is needed. This research should be
      focused on the effectiveness of innovative strategies directed to patients,
      individual professionals, teams, healthcare organizations, and finances. CLINICAL
      RELEVANCE: Implementation of evidence-based interventions is crucial to
      professional nursing and the quality and safety of patient care.

PMID- 19094145
TI  - Effect of abuse by a close family member on health.
AB  - PURPOSE: To examine the effects of physical, sexual, and emotional abuse on
      physical and psychological health among Icelandic women visiting an emergency
      department (ED) or high-risk prenatal care clinic (HRPCC). We hypothesized that
      the women's previous experience of abuse by a close family member and current
      experiences of abuse by an intimate partner, would predict their physical and
      psychological health. METHOD: A cross-sectional study design was used. Data were
      collected using questionnaires (e.g., Women Abuse Screening Tool (WAST) and
      semistructured interviews, from a sample of 208 women (101 visiting the ED and
      107 visiting the HRPCC). RESULTS: For the women seen in the ED, their experience
      of previous sexual abuse by a close family member, emotional abuse within the
      preceding year, and current abuse predicted the women's psychological health. For
      the women seen at the HRPCC, their previous experience of physical abuse, sexual
      abuse by a close family member, and being currently in an abusive relationship
      significantly predicted the women's psychological health. CONCLUSIONS: Women in
      Iceland, who are survivors of abuse, seek healthcare services from EDs and high
      risk prenatal clinics. The complex effects of both former and current abuse on
      women's health indicates the importance of regular screening for abuse against
      women. CLINICAL RELEVANCE: Offering appropriate interventions within emergency
      departments and high-risk prenatal clinics to women who are victims of abuse is
      vital.

PMID- 19094146
TI  - Predicting admissions for childhood asthma based on proximity to major roadways.
AB  - PURPOSE: This retrospective study is an investigation of the relationship between
      traffic exposure and childhood asthma exacerbations in a previously unstudied
      geographic area. We hypothesized that, controlling for selected demographic and
      social factors, exposure to traffic emissions would allow the prediction of
      hospital utilization for children with asthma. DESIGN: Using hospital and
      emergency department (ED) records, we investigated the relationship between
      proximity to major roadways and admissions for asthma exacerbations in the Fort
      Worth metropolitan area, designated as not attaining federal air health
      standards. The sample included 2,357 children from 1 to 12 years of age admitted
      for emergency or inpatient treatment in a 288-bed, nonprofit children's medical
      center in Fort Worth, Texas from January 1, 2004 to December 31, 2005. Data were
      analyzed using GIS mapping and logistic regression. METHODS: Deidentification
      data were collected from hospital databases after IRB approval and waiver of
      parental permission or patient consent. Student's t test was used to compare
      groups with and without primary asthma diagnosis on admission in respect to
      distance from major roadways. Logistic regression was used to model relationships
      between asthma admission and patients' characteristics, exposure to traffic, and
      social environment. FINDINGS: Controlling for several demographic factors, asthma
      occurrences were positively related to traffic exposures. On average, patients
      with asthma lived closer to major roadways than did patients who did not have
      asthma. Patients with asthma also tended to live in neighborhoods with more roads
      than did those who did not have asthma; 3/4 of the children admitted for asthma
      during the study period and less than 1/3 of the children admitted for nonasthma
      diagnoses lived within 1,500 meters of a major roadway (p=.0001). Controlling for
      other factors, every meter increase in proximity to major roadways produced 0.1%
      increase in likelihood of admission. CLINICAL RELEVANCE: Knowledge of risk
      factors and their relative magnitudes enable nurses to better tailor symptom
      management for individual patients.

PMID- 19094147
TI  - Adult protective services use for older adults at the time of hospital discharge.
AB  - PURPOSE: In this article a description is given of the use of adult protective
      services (APS) as a "safety net" by healthcare team members (HCTMs) when concerns
      were evident about an older adult's hospital discharge decisions. DESIGN AND
      METHODS: The study had a descriptive qualitative design and participants'
      perceptions of discharge destination decisions were explored. A total of 13 semi
      structured interviews were conducted with 7 HCTMs, who were the primary discharge
      planners for 13 frail older adults. FINDINGS: Themes that emerged were safety,
      "reconciling the differences,""letting them fail," having confidence in the
      family caregiver, and weighing the options. If HCTMs did not view the older
      adults' discharge decisions as safe, they would first try to persuade the older
      adults to change their minds, and if that failed, they would report the older
      adult to APS for follow-up. CONCLUSIONS: The APS system does not augment, nor
      does it replace, adequate hospital discharge planning. The use of the APS system
      as a safety net at the time of hospital discharge is a symptom of a grave problem
      that will only worsen as the number of elderly adults increases and adds stress
      to an already overburdened healthcare system. CLINICAL RELEVANCE: Access to
      health and social services at the time of hospital discharge is essential to the
      health and well-being of frail older adults; major gaps in services must be
      identified and corrected.

PMID- 19094148
TI  - The legacy of childhood sexual abuse and family adversity.
AB  - PURPOSE: To describe the process by which childhood adversity influences the life
      course of survivors of childhood sexual abuse. DESIGN: A community-based,
      qualitative, grounded-theory design. METHODS: In this grounded theory study, data
      were drawn from open-ended interviews conducted as part of a larger study of
      women's and men's responses to sexual violence. The current study indicates the
      experiences of 48 female and 40 male survivors of childhood sexual abuse and
      family adversity. Data were analyzed using the constant comparison method.
      FINDINGS: Participants described a sense of inheriting a life of abuse and
      adversity. The process by which childhood adversity influences the life course of
      adult survivors of childhood sexual abuse is labeled Living the Family Legacy.
      The theory representing the process of Living the Family Legacy includes three
      major life patterns: (a) being stuck in the family legacy, (b) being plagued by
      the family legacy, and (c) rejecting the family legacy/creating a new one.
      Associated with these life patterns are three processes by which participants
      passed on a legacy to others, often their children: (a) passing on the family
      legacy, (b) taking a stab at passing on a new legacy, and (c) passing on a new
      legacy. CONCLUSIONS: The legacy of abuse and adversity has a profound effect on
      the lives of survivors of childhood sexual abuse. There are several trajectories
      by which the influence of childhood adversity unfolds in the lives of adult
      survivors and by which the legacy is passed on to others. CLINICAL RELEVANCE: The
      model representing the theoretical process of Living the Family Legacy can be
      used by clinicians who work with survivors of childhood sexual abuse and
      childhood adversity, especially those who have parenting concerns.

PMID- 19094149
TI  - Breast-cancer-related lymphedema: information, symptoms, and risk-reduction
      behaviors.
AB  - PURPOSE: To explore the effect of providing lymphedema information on breast
      cancer survivors' symptoms and practice of risk-reduction behaviors. DESIGN: A
      cross-sectional design was used to obtain data from 136 breast-cancer survivors
      in New York City from August 2006 to May 2007. Descriptive statistics, t tests,
      chi-square tests, and correlations were calculated. METHODS: Data were collected
      using a demographic and medical information interview tool, two questions
      regarding status of receiving lymphedema information, the Lymphedema and Breast
      Cancer Questionnaire, and Lymphedema Risk-Reduction Behavior Checklist. FINDINGS:
      Fifty-seven percent of the participants reported that they received lymphedema
      information. On average, participants had three lymphedema-related symptoms. Only
      18% of participants were free of symptoms. Participants who received information
      reported significantly fewer symptoms (t=3.03; p<0.00) and practicing more risk
      reduction behaviors (t=2.42; p=0.01). CONCLUSIONS: Providing lymphedema
      information has an effect on symptom reduction and more risk-reduction behaviors
      being practiced among breast cancer survivors. CLINICAL RELEVANCE: In clinical
      practice, nurses and other healthcare professionals could consider taking the
      initiative to provide adequate and accurate information and engage breast-cancer
      survivors in supportive dialogues concerning lymphedema risk-reduction.

PMID- 19094150
TI  - Nurses' body size and public confidence in ability to provide health education.
AB  - PURPOSE: To replicate research about confidence level in receiving health
      teaching from either an overweight or a weight-appropriate RN. METHODS: A quasi
      experimental post-test only design was used. Participants were randomly assigned
      to be shown images of a nurse, either overweight or weight-appropriate, then
      asked to rate their confidence in health teaching received from that nurse.
      Descriptive statistics, t test for independent samples, and covariate analyses
      were performed. RESULTS: A significant difference in confidence p=0.000 was noted
      between participants who viewed the image of a weight-appropriate nurse and
      participants who viewed the image of an overweight nurse. CONCLUSIONS: Weight
      appropriate nurses may inspire more confidence in their teaching. Further study
      is indicated to explore the implications of these findings for practice. CLINICAL
      RELEVANCE: Nurses need to be conscious of clients' perceptions of weight when
      planning teaching interventions.

PMID- 19094151
TI  - Maternal perceptions of insufficient milk supply in breastfeeding.
AB  - PURPOSE: Improving the duration of exclusive breastfeeding is a national and
      international priority. Insufficient milk supply is one of the most commonly
      cited reasons for early cessation or decreased exclusivity in women who have
      initiated breastfeeding. This paper is an integrative review of current research
      pertaining to perceived insufficient milk (PIM). DESIGN AND METHODS: CINAHL,
      MEDLINE, and PubMed were searched combining "human milk" and "milk supply" and
      "perceived milk supply." Articles were limited to original research studies
      related to healthy, full-term breastfeeding dyads conducted over the past 10
      years. Critical review indicated robust findings, limitations, and gaps in this
      body of literature. FINDINGS: A lot of women discontinue breastfeeding during the
      first few weeks of the post-partum period because of PIM and approximately 35% of
      all women who wean early report PIM as the primary reason. Many women utilize
      infant satisfaction cues as their main indication of milk supply and many
      researchers, clinicians, and breast-feeding women do not evaluate actual milk
      supply. The relationships between PIM and socioeconomic or demographic variables
      as well as early breastfeeding behaviors have not been adequately addressed in
      the literature. CONCLUSIONS: Recommendations include improvement of maternal
      education about behaviors to ensure adequate supply, assessment of milk supply,
      and infant cues as well as further research into the root causes of PIM. CLINICAL
      RELEVANCE: Practitioners involved with maternal child health can improve their
      care of women and infants by understanding the subjective nature and questionable
      accuracy of PIM and changing assessment of milk supply.

PMID- 19094152
TI  - Evolution of a conceptual model for adaptation to chronic illness.
AB  - PURPOSE: To describe the evolution of "The Women to Women Conceptual Model for
      Adaptation to Chronic Illness." DESIGN: A three-phase, computer-based research
      intervention to provide support and health information to chronically ill middle
      aged women living in rural areas of the intermountain West. EVOLUTION OF A
      CONCEPTUAL MODEL: The path of the conceptualization of the WTW project was traced
      from a single concept to its present explanatory, multiconcept model consisting
      of three major adaptation constructs (environmental stimuli, psychosocial
      response, illness management) with related middle-range theoretical concepts
      (focal, contextual, and residual stimuli, psychosocial adaptation, chronic
      illness self-management, and quality of life) including empirical indicators and
      measures for each. CLINICAL RELEVANCE: As the computer-based intervention is
      maturing, we are demonstrating its efficacy in helping rural women to better
      manage chronic illness. At the completion of this study, the intervention should
      be adequately tested so that it could be adapted for use by advanced practice
      nurses especially those working with people in isolated rural areas.

PMID- 19094153
TI  - Managing the common problem of missing data in trauma studies.
AB  - PURPOSE: To provide guidance for managing the problem of missing data in clinical
      studies of trauma in order to decrease bias and increase the validity of findings
      for subsequent use. ORGANIZING CONSTRUCT: A thoughtful approach to missing data
      is an essential component of analysis to promote the clear interpretation of
      study findings. METHODS: Integrative review of relevant biostatistics, medical
      and nursing literature, and case exemplars of missing data analyses using
      multiple linear regression based upon data from the National Study on the Costs
      and Outcomes of Trauma (NSCOT) was used as an example. FINDINGS AND CONCLUSIONS:
      In studies of traumatically injured people, multiple imputed values are often
      superior to complete case analyses that might have significant bias. Multiple
      imputation can improve accuracy of the assessment and might also improve
      precision of estimates. Sensitivity analyses which implements repeated analyses
      using various scenarios may also be useful in providing information supportive of
      further inquiry. This stepwise approach of missing data could also be valid in
      studies with similar types or patterns of missing data. CLINICAL RELEVANCE: In
      interpreting and applying findings of studies with missing data, clinicians need
      to ensure that researchers have used appropriate methods for handling this issue.
      If suitable methods were not employed, nurse clinicians need to be aware that the
      findings may be biased.

PMID- 19094154
TI  - The lived experience of genocide rape survivors in Rwanda.
AB  - PURPOSE: The purpose of this study was to explore the lived experience of women
      who were raped during the 1994 genocide in Rwanda. METHODS: A phenomenological
      approach was used and this study was carried out in Rwanda in three different
      locations. The 7 participants took part in three semi-structured, individual
      interviews which were audiotaped. RESULTS: Participants reported many themes
      unique to Rwandan women survivors of genocide. These themes included violation by
      perceived inferiors, loss of dignity and respect, loss of identity, social
      isolation, loss of hope for the future (i.e., HIV/AIDS), the ongoing torture of
      rape babies, and developing a sense of community. CONCLUSIONS: Rwandan women
      survivors of the 1994 genocide have lived through unimaginable suffering. Limited
      information is available regarding the experiences of these rape survivors and
      this information could create awareness and some understanding of what these
      women endured. CLINICAL RELEVANCE: This study can help nurses to understand the
      sequelae of war and rape and thus have needed information which can be used to
      offer assistance to women in these circumstances.

PMID- 19094155
TI  - Association between nursing workload and mortality of intensive care unit
      patients.
AB  - PURPOSE: To investigate differences in mortality of intensive care unit (ICU)
      patients according to the ratio between total patient care demands and nurse
      staffing. DESIGN: Observational, prospective study. Patients consecutively
      admitted in the medical-surgical ICU of a Greek hospital over a 1-year period
      were enrolled. METHODS: The Therapeutic Intervention Scoring System (TISS)-28 was
      used for measuring patient care demands. Daily sum of TISS-28 of patients and
      daily number of nurses were considered for estimating median and peak patient
      exposure to nursing workload. According to the values of median and peak patient
      exposure to nursing workload, patients were divided into three groups (low,
      medium, and high). Logistic regression was used for evaluating the associations
      between mortality during ICU length of stay and median or peak patient exposure
      to nursing workload, after adjusting for patient clinical severity. FINDINGS: 396
      patients were included and 102 died. Differences in ICU mortality between high
      and low groups of median and peak patient exposure to nursing workload, although
      not statistically significant, were clinically remarkable, both when all patients
      were studied and when medical and surgical patients were separately studied.
      CONCLUSIONS: Consideration of individual differences in patient acuity might add
      sensitivity to the detection of associations between nurse understaffing and ICU
      mortality. CLINICAL RELEVANCE: The findings indicate that not only differences
      among nurse characteristics, but also differences in patient care demands, are
      important when investigating the effect of nurse understaffing on mortality of
      ICU patients. Proper nurse staffing levels should be based on the estimation of
      total patient acuity, rather than on the absolute number of patients.

PMID- 19094156
TI  - Development of a self-report instrument to measure patient safety attitudes,
      skills, and knowledge.
AB  - PURPOSE: To describe the development and psychometric testing of the Patient
      Safety Attitudes, Skills and Knowledge Scale (PS-ASK). METHODS: Content validity
      of a 35-item instrument was established by a panel of experts. The instrument was
      pilot tested on 285 nursing students. Principal components analysis (PCA) with
      varimax rotation was conducted, and Cronbach's alphas were examined. Paired
      samples t-tests were used to show responsiveness of the scales pre- and post
      patient safety curriculum. RESULTS: The final instrument consists of 26 items and
      three separate scales: attitudes, skills, and knowledge. The attitudes and skills
      scales each had a three-factor solution. The knowledge items had a one-factor
      solution. Both skills and knowledge were significantly increased at Time 2
      (p<0.001). CONCLUSIONS: The skills and knowledge subscales had satisfactory
      internal consistency reliability, evidence for construct validity, and
      responsiveness for use as independent scales in future studies. The attitudes
      subscale needs further refinement before implementation. Comparison with other
      measures of patient safety skills (e.g., observation) and knowledge are
      warranted. CLINICAL RELEVANCE: A tool to measure clinicians' attitudes, skills,
      and knowledge about patient safety might be useful to evaluate nurses and other
      clinicians during educational preparation and in practice.

PMID- 19094157
TI  - Experience, time investment, and motivators of nursing journal peer reviewers.
AB  - PURPOSE: To describe nursing journal reviewers' professional backgrounds,
      reviewing experience, time investment, and perceptions of their role. DESIGN:
      Exploratory descriptive cross-sectional study. METHODS: A 69-question survey
      containing both fixed-option and open-ended questions and accessed via the World
      Wide Web was completed by 1,675 nursing journal reviewers who had been invited to
      participate by editors of 52 nursing journals. FINDINGS: Participants were from
      44 countries, with 74% from the US, and 90% were nurses. The majority were
      doctorally prepared academics who were involved in research. They reported
      spending an average of 5 hours on each critique and completed an average of 7-8
      reviews per year. The most common reason reported for becoming involved was
      personal contact with an editor. Lack of time because of competing work
      commitments was the most commonly cited barrier to reviewing and negative aspect
      of the role. The most common positive aspect was keeping up to date with the
      field. CONCLUSIONS: Nursing journal peer reviewers express rewards and challenges
      similar to those reported elsewhere for biomedical journal reviewers. Based on
      these findings, editors might consider new approaches to recruiting and
      supporting reviewers, and potential reviewers might gain insight into the role.
      Support of these distinguished scholars in this important role is critical to
      sustain the quality of scholarship that informs nursing practice, education, and
      research. CLINICAL RELEVANCE: Clinicians, researchers, and educators who rely on
      the quality of the articles published in nursing journals can learn from this
      survey about the background and experiences of those who protect that quality by
      providing expert feedback to authors and editors.

PMID- 19094159
TI  - Aggrenox (Asasantin retard)-induced Stevens-Johnson syndrome.

PMID- 19094158
TI  - The use and potential abuse of anticholinergic antiparkinson drugs in Norway: a
      pharmacoepidemiological study.
AB  - WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT: Anticholinergic antiparkinson drugs are
      used to ameliorate extrapyramidal symptoms caused by either Parkinson's disease
      or antipsychotic drugs, but their use in the treatment of Parkinson's disease is
      assumed to be in decline. Patients with psychotic conditions have a high
      prevalence of abuse of drugs, including anticholinergic antiparkinson drugs. WHAT
      THIS STUDY ADDS: Anticholinergic antiparkinson drugs in Norway were primarily
      prescribed to patients using antipsychotic medication. The risk of abuse of this
      group of drugs was small, even among patients who probably abused other drugs.
      AIMS: The use of anticholinergic antiparkinson drugs is assumed to have shifted
      from the therapy of Parkinson's disease to the amelioration of extrapyramidal
      adverse effects induced by antipsychotic drugs. There is a considerable body of
      data suggesting that anticholinergic antiparkinson drugs have a potential for
      abuse. The aim was to investigate the use and potential abuse of this class of
      drugs in Norway. METHODS: Data were drawn from the Norwegian Prescription
      Database on sales to a total of 73 964 patients in 2004 of biperiden and
      orphenadrine, and use in patients with Parkinson's disease or in patients who
      were also prescribed antipsychotic agents. Possible abuse of these drugs was
      assessed by the level of use, skewedness of use, indications of drug-seeking
      behaviour and concomitant use of benzodiazepine tranquillizers, a group of
      prescription drugs with a recognized potential for abuse. RESULTS:
      Anticholinergic antiparkinson drugs were prescribed to 4.5% of all outpatients
      who used antipsychotic drugs. This outnumbered sales to patients with Parkinson's
      disease by >20 to 1. We found indications of abuse of benzodiazepine
      tranquillizers among patients using antipsychotics, but there were no clear
      indications of abuse of anticholinergics, even among patients who were strongly
      suspected of abuse of benzodiazepines. CONCLUSIONS: Anticholinergic antiparkinson
      drugs were used primarily by patients with psychotic illnesses. These patients
      have a very high prevalence of legal and illegal drug abuse, but the risk of
      abuse of anticholinergic antiparkinson drugs seemed small.

PMID- 19094160
TI  - Influence of domperidone on pharmacokinetics, safety and tolerability of the
      dopamine agonist rotigotine.
AB  - WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT: Rotigotine transdermal patch is a new
      non-ergolinic dopamine agonist developed for the treatment of Parkinson's disease
      and restless legs syndrome. Peripheral dopaminergic side-effects of dopamine
      agonists such as nausea and vomiting can be prevented by the antiemetic agent
      domperidone. WHAT THIS STUDY ADDS: The study results show no evidence for an
      interaction of domperidone on bioavailability and steady-state pharmacokinetics
      of transdermal rotigotine. Co-administration of domperidone and rotigotine does
      not require dose adjustments for rotigotine transdermal patch. AIMS: To evaluate
      the influence of the antiemetic agent domperidone on steady-state
      pharmacokinetics, safety and tolerability of multiple-dose treatment of the
      transdermally applied non-ergolinic dopamine agonist rotigotine. METHODS: Sixteen
      healthy male subjects (mean age 30.3 years) participated in a randomized, two-way
      crossover clinical trial. Treatment A consisted of transdermal rotigotine patch
      (2 mg (24 h)(-1), 10 cm(2), total drug content 4.5 mg) applied daily for 4 days,
      and concomitant oral domperidone (10 mg t.i.d.) for 5 days. For treatment B,
      subjects received only transdermal rotigotine treatment (daily for 4 days).
      Pharmacokinetic variables describing systemic exposure and renal elimination of
      rotigotine and metabolites, and safety and tolerability of the treatment were
      assessed. RESULTS: The primary steady-state pharmacokinetic parameters (C(max,ss)
      and AUC((0-24),ss)) were similar with or without co-administration of
      domperidone. Geometric mean ratios were close to 1 and respective 90% confidence
      intervals were within the acceptance range of bioequivalence (0.8, 1.25):
      C(max,ss) 0.96 (0.86, 1.08) and AUC((0-24),ss) 0.97 (0.87, 1.08). t(max,ss),
      t(1/2), secondary parameters calculated on days 4/5 after repeated patch
      application (C(min,ss), C(ave,ss), AUC((0-tz))) and renal elimination for
      unconjugated rotigotine and its metabolites were also similar with and without
      comedication of domperidone. A reduction in the dopaminergic side-effect nausea
      was seen with domperidone comedication. CONCLUSIONS: No changes of
      pharmacokinetic parameters describing systemic exposure and renal elimination of
      rotigotine were observed when domperidone was administered concomitantly with
      rotigotine. The lack of pharmacokinetic interactions indicates that a dose
      adjustment of rotigotine transdermal patch is not necessary with concomitant use
      of domperidone.

PMID- 19094161
TI  - Tolerability, pharmacokinetics and night-time effects on postural sway and
      critical flicker fusion of gaboxadol and zolpidem in elderly subjects.
AB  - WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT: Body sway increases in older adults and
      may lead to an increase in the risk of falling. The problem of impaired stability
      in the elderly may be compounded by the use of hypnotics, which have been
      associated with an increased risk of next-day falls as well as drowsiness. The
      potential adverse effects of hypnotic drugs on steadiness may be exacerbated
      during the night, in the event that an individual needs to get out of bed. WHAT
      THIS STUDY ADDS: This study examines the effects of gaboxadol (an investigational
      treatment for insomnia), zolpidem (a current hypnotic included as an active
      control) and placebo on body sway and attention/information processing ability
      following bedtime dosing in elderly subjects who were woken during the night for
      assessments. Zolpidem and gaboxadol increased body sway at various time points
      during the night relative to placebo; at 1.5 h post dose, the time of peak
      concentrations of both drugs, gaboxadol produced less impairment than zolpidem.
      Compared with placebo, neither gaboxadol nor zolpidem impaired
      attention/information-processing ability as assessed by critical flicker fusion.
      AIMS: To evaluate tolerability, pharmacokinetics and night-time effects on body
      sway and critical flicker fusion (CFF) of gaboxadol following bedtime dosing in
      healthy elderly subjects. METHODS: Subjects (17 women, seven men) aged 65-75
      years received gaboxadol 10 mg, zolpidem 5 mg (active control) or placebo at
      22.00 h in a three-period, randomized, double-blind crossover study. They were
      awakened during the night for evaluation of body sway and CFF. Pharmacokinetics
      of gaboxadol were assessed during a fourth single-blind treatment period. Adverse
      events were recorded throughout the study. RESULTS: The number of subjects with
      adverse events was 14 for gaboxadol 10 mg, seven for zolpidem and nine for
      placebo; most were mild or moderate in intensity. Two women discontinued the
      study following gaboxadol; one vomited and one experienced a severe vasovagal
      syncope after venepuncture. Mean gaboxadol t(max) was 2 h, t((1/2)) was 1.7 h,
      AUC(0-infinity) was 430 ng.h ml(-1) and C(max) was 139 ng ml(-1). At 1.5 h and 4
      h post dose, zolpidem increased body sway relative to placebo (P < 0.01).
      Gaboxadol increased body sway at 4 h (P < 0.001) and 8 h (P < 0.05) relative to
      placebo. At 1.5 h, the time point closest to peak drug concentrations, zolpidem
      increased body sway compared with gaboxadol (P < 0.01). Gaboxadol and zolpidem
      had no effects on CFF vs. placebo. CONCLUSIONS: A bedtime dose of gaboxadol 10 mg
      was generally well tolerated. Changes in body sway at 1.5 h after bedtime dosing
      were smaller with gaboxadol 10 mg than with zolpidem 5 mg, whereas changes were
      similar at 4 h for both treatments and returned to near baseline at 8 h.

PMID- 19094162
TI  - What is the scale of prescribing errors committed by junior doctors? A systematic
      review.
AB  - AIMS: Prescribing errors are an important cause of patient safety incidents,
      generally considered to be made more frequently by junior doctors, but prevalence
      and causality are unclear. In order to inform the design of an educational
      intervention, a systematic review of the literature on prescribing errors made by
      junior doctors was undertaken. METHODS: Searches were undertaken using the
      following databases: MEDLINE; EMBASE; Science and Social Sciences Citation Index;
      CINAHL; Health Management Information Consortium; PsychINFO; ISI Proceedings; The
      Proceedings of the British Pharmacological Society; Cochrane Library; National
      Research Register; Current Controlled Trials; and Index to Theses. Studies were
      selected if they reported prescribing errors committed by junior doctors in
      primary or secondary care, were in English, published since 1990 and undertaken
      in Western Europe, North America or Australasia. RESULTS: Twenty-four studies
      meeting the inclusion criteria were identified. The range of error rates was 2
      514 per 1000 items prescribed and 4.2-82% of patients or charts reviewed.
      Considerable variation was seen in design, methods, error definitions and error
      rates reported. CONCLUSIONS: The review reveals a widespread problem that does
      not appear to be associated with different training models, healthcare systems or
      infrastructure. There was a range of designs, methods, error definitions and
      error rates, making meaningful conclusions difficult. No definitive study of
      prescribing errors has yet been conducted, and is urgently needed to provide
      reliable baseline data for interventions aimed at reducing errors. It is vital
      that future research is well constructed and generalizable using standard
      definitions and methods.

PMID- 19094163
TI  - High voriconazole trough levels in relation to hepatic function: how to adjust
      the dosage?

PMID- 19094164
TI  - The credit crunch - the potential impact on older people.

PMID- 19094165
TI  - Reaction time during semi-automated kinetic perimetry (SKP) in patients with
      advanced visual field loss.
AB  - PURPOSE: This study aimed to evaluate reaction time (RT) in patients with
      advanced visual field (VF) loss using semi-automated kinetic perimetry (SKP).
      METHODS: Seventy-eight patients with advanced VF loss caused by glaucoma (31) or
      retinitis pigmentosa (19), homonymous VF loss caused by post-chiasmal lesions
      (18) and unilateral anterior ischaemic optic neuropathy (AION) (10) were examined
      with SKP (Octopus 101 perimeter). One eye in each patient was enrolled.
      Additionally, VFs in the 10 healthy fellow eyes of the patients with AION were
      compared with those in the 10 affected eyes. Reaction time was assessed during
      the SKP session by presenting kinetic stimuli (III4e) with constant angular
      velocities of 3 degrees /second moving linearly along so-called 'RT vectors' at
      four different locations inside the III4e isoptre. Each stimulus presentation was
      repeated four times in randomized order. RESULTS: The geometric mean RT was 794
      ms (95% reference interval [RI] 391-1615 ms) in patients with glaucoma, 702 ms
      (95% RI 306-1608 ms) in patients with retinitis pigmentosa and 675 ms (95% RI 312
      1460 ms) in patients with hemianopia. Increases in RT for every 1 degree of
      eccentricity were 1%, 0.9% and 0.4%, respectively. The geometric mean RT in the
      10 patients with unilateral optic neuropathy was 644 ms in affected eyes and 435
      ms in unaffected eyes, reflecting an increase of 51% (95% confidence interval 42
      62%). CONCLUSIONS: We found substantial inter-subject variability in RT in
      patients with advanced VF loss. It is possible to correct the position of the
      isoptres by assessing individual RT. There were no relevant differences in RT
      between the disease groups. Reaction time increases with eccentricity. In
      monocular disease (AION), RT is prolonged, compared with in healthy fellow eyes.
      However, in clinical routine the RT-related displacement of isoptres is
      negligible in the vast majority of cases.

PMID- 19094166
TI  - Effect of acute postural variation on diabetic macular oedema.
AB  - PURPOSE: This study aimed to study the pathophysiology of diabetic macular oedema
      (DMO) by analysis of concomitant changes in macular volume (MV), mean arterial
      blood pressure (MABP), intraocular pressure (IOP), and retinal artery and vein
      diameters in response to acute postural changes in patients with DMO and healthy
      subjects. METHODS: Thirteen patients with DMO (13 eyes) and five healthy subjects
      (five eyes) were examined after resting in a chair for 15 mins using optical
      coherence tomography to measure MV and fundus photography to assess retinal
      vessel diameters. The patients then lay down for 60 mins, during which they were
      examined repeatedly before they were reseated and examined again. Intraocular
      pressure was measured using pulse-air tonometry, arterial blood pressure by
      sphygomanometry and fluid columns using rulers and a spirit level. RESULTS: In
      healthy subjects, retinal artery (p = 0.02) and vein (p = 0.001) diameters
      decreased when subjects lay down, whereas MV remained stable. In patients with
      DMO, no orthostatic variation in retinal vessel diameters could be demonstrated,
      whereas MV had increased by 2.4 +/- 0.6% (mean +/- standard error of the mean; p
      = 0.006) 50 mins after assuming a recumbent position. In both healthy subjects
      and DMO patients, MABP decreased and IOP increased in a recumbent position, with
      no significant difference between the groups. CONCLUSIONS: The increase in MV
      that occurs in DMO when changing from a seated to a recumbent position is
      associated with a failure of retinal artery contraction, a response seen in
      healthy subjects that appears to counter-regulate the increase in ocular
      perfusion pressure caused by assuming a recumbent position.

PMID- 19094167
TI  - Macular appearance after diabetic vitrectomy for fibrovascular proliferation: an
      optical coherence tomography study.
AB  - PURPOSE: To investigate morphological variations in the macular area with optical
      coherence tomography (OCT) after vitrectomy for diabetic fibrovascular
      proliferation. METHODS: We reviewed 108 cases using OCT 7-15 months after
      vitrectomy. Of these, 32 received OCT within 3 months postoperatively.
      Morphological variations were categorized and correlated with visual outcome.
      RESULTS: Only 24 cases (21.4%) had no obvious abnormalities. The most frequent
      findings were epiretinal membrane (52.8%), macular thickening (37.0%) and macular
      cysts (28.7%). Multivariate regression showed that diffuse macular thickening,
      loss of foveal depression and diffuse retinal thinning were significantly
      associated with poor visual acuity. Sequential OCT (< 3 and >or= 7 months)
      revealed that epiretinal membrane and oedema outside of fovea changed
      significantly between two examinations. CONCLUSION: OCT may identify diverse
      morphological changes in the macular area after diabetic vitrectomy for
      fibrovascular proliferation. Macular appearance may change over time, and certain
      types of morphological changes may be associated with poor visual function.

PMID- 19094168
TI  - Repeated measures of macular pigment optical density to test reproducibility of
      heterochromatic flicker photometry.
AB  - PURPOSE: To report the reproducibility of macular pigment optical density (MPOD)
      values assessed with heterochromatic flicker photometry (HFP) in healthy
      individuals. METHODS: Twenty-four volunteers from our department underwent MPOD
      testing of both eyes by flicker photometry on three separate occasions. To test
      reproducibility of MPOD, the coefficient of variance was calculated separately
      for right and left eyes. In addition, we investigated MPOD averages of right and
      left eyes and interocular correlations (Pearson's r) at every visit. RESULTS: The
      mean MPODs at the first visit were 0.61 +/- 0.24 and 0.72 +/- 0.27 in right and
      left eyes, respectively. Mean values of 0.58 +/- 0.29 and 0.60 +/- 0.21 (second
      visit) and 0.62 +/- 0.27 and 0.63 +/- 0.24 (third visit) were assessed for right
      and left eyes, respectively. Differences of the mean values between eyes were not
      significant. Correlations were weak at visits one and two (r = 0.49, p < 0.014
      and r = 0.43, p < 0.038, respectively) and moderate at visit three (r = 0.58, p <
      0.003). The coefficients of variance were 36.1% and 23% for right and left eyes,
      respectively. CONCLUSION: Our mean MPODs are higher and the interocular
      correlations weaker compared to the literature. The coefficient of variance in
      both eyes is high and does not imply good reproducibility of obtained MPOD
      values.

PMID- 19094169
TI  - Bilateral progressive necrotizing retinochoroiditis in an immunocompromised
      patient: histopathological diagnosis.

PMID- 19094170
TI  - Actinomycotic canaliculitis: resolution following surgery and short topical
      antibiotic treatment.
AB  - PURPOSE: This study aimed to study the incidence and clinical characteristics of
      patients diagnosed with actinomycotic canaliculitis in Iceland. METHODS: We
      present a nationwide, retrospective case series for which cases were identified
      by searches of hospital diagnostic registries and pathology databases. Case
      histories were reviewed and histopathological analysis repeated to confirm the
      diagnosis. RESULTS: Nine cases of actinomycotic canaliculitis were diagnosed in
      Iceland during 1988-2007. Subjects included six women and three men and
      represented 16% of all patients diagnosed with actinomycosis in the country. The
      incidence was 0.16 cases/100 000 inhabitants/year. Age-specific incidence rates
      were 0.59 cases/100 000 inhabitants/year for the 40-59-year-old age group and
      1.37 cases/100 000 inhabitants/year for individuals aged 60-79 years. All
      patients underwent a three-way snip procedure and 1 week of topical antibacterial
      therapy. CONCLUSIONS: Actinomycotic canaliculitis is an uncommon condition which
      frequently eludes diagnosis. Topical antibiotics for 1 week may be sufficient
      following surgery, a finding which contrasts with previous reports.

PMID- 19094171
TI  - Intravitreal bevacizumab (Avastin) for neovascular age-related macular
      degeneration in treatment-naive patients.
AB  - PURPOSE: To report the effects of intravitreal bevacizumab (Avastin) in treatment
      naive patients with exudative age-related macular degeneration (ARMD) assessed by
      visual acuity (VA), optical coherence tomography (OCT) and contrast sensitivity.
      METHODS:  A prospective, uncontrolled, pilot study of 26 eyes of 26 patients, all
      previously treatment-naive to photodynamic therapy, argon laser or anti-vascular
      endothelial growth factor (VEGF), were treated with one or more intravitreal
      injections of 1.25 mg bevacizumab. Of the 26 patients, 15 (57.7%) had occult
      choroidal neovascularization (CNV), 6 (23.1%) had predominantly classic CNV and 5
      (19.2%) had minimally classic CNV. Ophthalmic outcome measures included changes
      in standardized Early Treatment Diabetic Research Study (ETDRS) VA, contrast
      sensitivity and OCT. The patients were examined at baseline and 1 week, 6 weeks,
      3 months and 6 months after the first injection. Re-treatment was given on an 'as
      needed' basis. RESULTS:  Twenty-four eyes of 24 patients completed 6 months of
      follow-up. Two patients chose to discontinue the study. Mean ETDRS VA score
      improved from 55 letters at baseline to 60 letters at 1 week (P < 0.01) and to 61
      letters at 6 weeks (P < 0.01). No significant improvement in VA from baseline was
      found after 3 and 6 months. Patients with pigment epithelial detachment (PED) had
      a significantly worse outcome in VA at 6 months. Contrast sensitivity improved
      from baseline to 3 or 6 months, but this improvement was not statistically
      significant. Mean macular thickness decreased significantly from baseline to all
      follow-up examinations (P < 0.01). CONCLUSION:  Mean ETDRS VA improved
      significantly after 1 and 6 weeks; thereafter, it remained stable throughout the
      study period. Macular thickness improved significantly at all time points. The
      results indicate that 1.25 mg intravitreal bevacizumab is associated with
      functional as well as morphological improvement among treatment-naive ARMD
      patients.

PMID- 19094172
TI  - Conjunctival impression cytology and tear-film changes in patients with familial
      Mediterranean fever.
AB  - PURPOSE: To evaluate the ocular surface changes and tear-film functions in
      patients with familial Mediterranean fever (FMF). METHODS: This prospective case
      control clinical study examined 35 patients with FMF (group 1) and 35 controls
      (group 2). All patients underwent a full ophthalmological examination. Ocular
      surface changes were evaluated by determining cell content of surface
      conjunctival epithelium using conjunctival impression cytology and tear-film
      functions using Schirmer-I, break-up time (BUT), corneal fluorescein and Rose
      Bengal tests. Subjective ocular complaints were scored with a four-point scale.
      Between-group results were compared. RESULTS: In group 1, impression cytology
      revealed grade 0 changes in 15 eyes, grade 1 changes in 11 eyes and grade 2
      changes in nine eyes in group 1; in group 2, it revealed grade 0 changes in 27
      eyes, grade 1 changes in five eyes and grade 2 changes in three eyes (p = 0.013).
      Mean goblet cell density was 765 +/- 45 cells/mm(2) in group 1 and 1730 +/- 100
      cells/mm(2) in group 2 (P < 0.001). Mean results on the Schirmer-I test results
      were 17.36 +/- 3.18 mm in group 1 and 19.60 +/- 4.17 mm in group 2 (p = 0.364).
      Mean BUT was 8.20 +/- 1.60 seconds in group 1 and 9.93 +/- 2.33 seconds in group
      2 (p = 0.001). Mean corneal fluorescein and Rose Bengal staining scores were 3.26
      +/- 1.67 and 0.96 +/- 0.71 in group 1 and 1.37 +/- 0.34 and 0.40 +/- 0.49 in
      group 2 (p = 0.037, p = 0.005). The presence of subjective ocular complaints was
      more frequent in group 1 than in group 2. CONCLUSION: Despite normal tear
      production, the ocular surface and tear-film functions of FMF patients differ
      from those of healthy individuals. These changes may be related to the chronic
      inflammatory nature of FMF.

PMID- 19094173
TI  - Baerveldt glaucoma implants in the management of refractory glaucoma after
      vitreous surgery.
AB  - PURPOSE: To examine the effectiveness and safety of Baerveldt glaucoma implants
      in eyes with refractory glaucoma following vitrectomy. METHODS: We performed a
      retrospective study of a non-comparative case series of 30 eyes of 30 patients
      who had undergone the implantation of a Baerveldt glaucoma device. All eyes
      (30/30) had a minimum follow-up of 6 months, and 16/30 (53%) had a follow-up of
      24 months. Surgical success was defined as intraocular pressure (IOP) < 22 mmHg
      on the last two follow-up visits with or without glaucoma medication and a
      decrease in IOP of at least 20% compared to preoperative values with or without
      glaucoma medication. RESULTS: The mean IOP before implantation of a Baerveldt
      glaucoma device was 30 mmHg [+/- 11.4 mmHg standard deviation (SD)] with
      maximally tolerated medical therapy. Six months after implantation of the
      Baerveldt glaucoma device, the mean IOP was 17.3 mmHg (+/- 6.7 mmHg SD) and the
      mean number of glaucoma medications had gone down from 3.0 (+/- 0.4 SD) to 0.3
      (+/- 0.3 SD). Successful outcomes were found in 24 eyes (80%). Small
      complications occurred in six eyes (20%): transient postoperative hypotony (17%)
      and tube retraction (3%). Larger complications occurred in another six eyes
      (20%): corneal decompensation requiring keratoplasty (7%), suprachoroidal
      haemorrhage (3%) and persistently high IOP (10%). CONCLUSION: Baerveldt glaucoma
      devices are a valid treatment option in eyes with refractory glaucoma after
      vitreous surgery, although failure occurred in 20% of our patients. Transient
      complications occurred in 20% and severe complications in another 20%.

PMID- 19094174
TI  - Hemodynamic effects of PEEP in a porcine model of HCl-induced mild acute lung
      injury.
AB  - BACKGROUND: Positive end-expiratory pressure (PEEP) and sustained inspiratory
      insufflations (SI) during acute lung injury (ALI) are suggested to improve
      oxygenation and respiratory mechanics. We aimed to investigate the hemodynamic
      effects of PEEP with and without alveolar recruiting maneuver in a mild ALI model
      induced by inhalation of hydrochloric acid. METHODS: Thirty-two pigs were
      randomly allocated into four groups (Control-PEEP, Control-SI, ALI-PEEP and ALI
      SI). ALI was induced by intratracheal instillation of hydrochloric acid. PEEP
      values were progressively increased and decreased from 5, 10, 15 and 20 cmH2O in
      all groups. Three SIs maneuvers of 30 cmH2O for 20 s were applied to the
      assignable groups between each PEEP level. Transesophageal echocardiography
      (TEE), global hemodynamics, oxygenation indexes and gastric tonometry were
      measured 5 min after the maneuvers had been concluded and at each established
      value of PEEP (5, 10, 15 and 20 cmH2O). RESULTS: The cardiac index, ejection
      fraction and end-diastolic volume of right ventricle were significantly (P <
      0.001) decreased with PEEP in both Control and ALI groups. Left ventricle
      echocardiography showed a significant decrease in end-diastolic volume at 20
      cmH2O of PEEP (P < 0.001). SIs did not exert any significant hemodynamic effects
      either early (after 5 min) or late (after 3 h). CONCLUSIONS: In a mild ALI model
      induced by inhalation of hydrochloric acid, significant hemodynamic impairment
      characterized by cardiac function deterioration occurred during PEEP increment,
      but SI, probably due to low applied values (30 cmH2O), did not exert further
      negative hemodynamic effects. PEEP should be used cautiously in ALI caused by
      acid gastric content inhalation.

PMID- 19094175
TI  - Persistent pain after groin hernia surgery: a qualitative analysis of pain and
      its consequences for quality of life.
AB  - BACKGROUND: Despite a high prevalence of persistent groin pain after hernia
      repair, the specific nature of the pain and its clinical manifestation are poorly
      known. The aim of this study was to determine the type of post-herniorrhaphy pain
      and its influence on daily life. METHODS: In order to assess long-term pain
      qualitatively and to explore how it affects quality of life, 100 individuals with
      persisting pain, identified in a cohort study of patients operated for groin
      hernia, were neurologically examined, along with 100 pain-free controls matched
      for age, gender and type of operation. The patients were asked to answer the SF
      36 questionnaire, the hospital anxiety and depression scale, the Swedish Scales
      of Personality (SSP) and a standardised questionnaire for assessing everyday life
      coping. The patients were approached approximately 4.9 years after surgery.
      RESULTS: Twenty-two patients from the pain group had become pain free by the time
      of examination, whereas 76 patients still had pain, of whom 47 (68%) suffered
      from neuropathic pain and 11 from nociceptive pain. The remaining patients
      suffered from mixed pain, neuropathic and nociceptive, or were found to have
      another reason for pain. All dimensions of SF-36 were poorer for the pain group
      than the control group. CONCLUSION: Persistent post-herniorrhaphy pain is mainly
      neuropathic and has a substantial impact on health-related quality of life.

PMID- 19094176
TI  - Blood leucocyte cytokine production after LPS stimulation at different
      concentrations of glucose and/or insulin.
AB  - BACKGROUND: Previous studies have indicated that alterations in blood glucose
      and/or insulin levels modify the inflammatory response. The purpose of this study
      was to elucidate whether increased levels of glucose and/or insulin influence the
      activation pattern of blood leucocytes and their production of cytokines in
      vitro. METHODS: Venous blood was obtained from eight healthy male volunteers
      after an overnight fast. Glucose and/or insulin were added to aliquots of whole
      blood to increase the blood glucose concentration by 5 or 20 mmol/l and/or the
      insulin concentration by 6 or 30 nmol/l, respectively, before stimulation with E.
      coli lipopolysaccharide (LPS) at concentrations of 10, 100 or 1000 ng/ml. The
      samples were subsequently incubated at 37 degrees C for 6 h before cytokine
      measurements. After centrifugation the levels of interleukins (IL)-1beta, IL-6,
      IL-8, IL-10 and tumour necrosis factor (TNF)-alpha were measured in plasma using
      enzyme-linked immuno-sorbent assays. The results were compared with cytokine
      levels in parallel control samples to which only identical amounts of LPS were
      added. RESULTS: The LPS-stimulated production of IL-1beta was significantly
      reduced by on average 26% in samples to which glucose 20 mmol/l was added;
      addition of insulin and/or glucose 5 mmol/l had no apparent effect on the IL
      1beta production at any LPS concentration. The levels of IL-6, IL-8, IL-10 and
      TNF-alpha were not manifestly altered by addition of glucose and/or insulin at
      any LPS concentration. CONCLUSION: A substantial increase in blood glucose
      concentration changed the IL-1beta production, but not the production of other
      cytokines, in response to LPS stimulation.

PMID- 19094177
TI  - Tezosentan normalizes hepatomesenteric perfusion in a porcine model of cardiac
      tamponade.
AB  - BACKGROUND: To investigate endothelin-1 (ET-1)-dependent hepatic and mesenteric
      vasoconstriction, and oxygen and lactate fluxes in an acute, fixed low cardiac
      output (CO) state. METHODS: Sixteen anesthetized, mechanically ventilated pigs
      were studied. Cardiac tamponade was established to reduce portal venous blood
      flow (Q(PV)) to 2/3 of the baseline value. CO, hepatic artery blood flow (Q(HA)),
      Q(PV), hepatic laser-Doppler flow (LDF), hepatic venous and portal pressure, and
      hepatic and mesenteric oxygen and lactate fluxes were measured. Hepatic arterial
      (R(HA)), portal (R(HP)) and mesenteric (R(mes)) vascular resistances were
      calculated. The combined ET(A)-ET(B) receptor antagonist tezosentan (RO 61-0612)
      or normal saline vehicle was infused in the low CO state. Measurements were made
      at baseline, after 30, 60, 90 min of tamponade, and 30, 60, 90 min following the
      infusion of tesozentan at 1 mg/kg/h. RESULTS: Tamponade decreased CO, Q(PV),
      Q(HA), LDF, hepatic and mesenteric oxygen delivery, while hepatic and mesenteric
      oxygen extraction and lactate release increased. R(HA), R(HP) and R(mes) all
      increased. Ninety minutes after tesozentan, Q(PV), LDF and hepatic and mesenteric
      oxygen delivery and extraction increased approaching baseline values, but no
      effect was seen on CO or Q(HA). Hepatic and mesenteric handling of lactate
      converted to extraction. R(HA), R(HP) and R(mes) returned to baseline values. No
      changes were observed in these variables among control animals not receiving
      tesozentan. CONCLUSION: In a porcine model of acute splanchnic hypoperfusion,
      unselective ET-1 blockade restored hepatomesenteric perfusion and reversed
      lactate metabolism. These observations might be relevant when considering liver
      protection in low CO states.

PMID- 19094178
TI  - Effect of the preliminary hydration on gastric emptying time for water in healthy
      volunteers.
AB  - BACKGROUND: International guidelines allow healthy patients to drink clear liquid
      up to 2 h before general anesthesia. Recently, MRI measurements have been used
      for tracking gastric volume in humans. Hence, we used MRI to examine the gastric
      emptying rate of water in healthy volunteers with or without prior water loading.
      METHODS: Fifteen healthy volunteers were enrolled. The participants had MRI
      examinations on separate days under two different protocols: The preliminary
      hydration protocol (group H) and the water restriction protocol (group R). After
      the intake of water, MR imaging was performed every 10 min for 60 min. The
      gastric content was outlined as area of interest (AOI), and the AOI area of each
      slice was summated to calculate the volume of gastric contents. RESULTS: The 50%
      reduction time of gastric volume in group R and group H was 18+/-9 and 16+/-8 min
      (mean+/-SD), respectively. There were no significant changes between the two
      groups. CONCLUSION: The gastric emptying time for water evaluated with MRI was
      not affected by preliminary hydration, which shows the safety of repeated oral
      hydrations in the pre-operative period.

PMID- 19094180
TI  - Loss of translation elongation factor (eEF1A2) expression in vivo differentiates
      between Wallerian degeneration and dying-back neuronal pathology.
AB  - Wallerian degeneration and dying-back pathology are two well-known cellular
      pathways capable of regulating the breakdown and loss of axonal and synaptic
      compartments of neurons in vivo. However, the underlying mechanisms and molecular
      triggers of these pathways remain elusive. Here, we show that loss of translation
      elongation factor eEF1A2 expression in lower motor neurons and skeletal muscle
      fibres in homozygous Wasted mice triggered a dying-back neuropathy. Synaptic loss
      at the neuromuscular junction occurred in advance of axonal pathology and by a
      mechanism morphologically distinct from Wallerian degeneration. Dying-back
      pathology in Wasted mice was accompanied by reduced expression levels of the zinc
      finger protein ZPR1, as found in other dying-back neuropathies such as spinal
      muscular atrophy. Surprisingly, experimental nerve lesion revealed that Wallerian
      degeneration was significantly delayed in homozygous Wasted mice; morphological
      assessment revealed that approximately 80% of neuromuscular junctions in deep
      lumbrical muscles at 24 h and approximately 50% at 48 h had retained motor nerve
      terminals following tibial nerve lesion. This was in contrast to wild-type and
      heterozygous Wasted mice where < 5% of neuromuscular junctions had retained motor
      nerve terminals at 24 h post-lesion. These data show that eEF1A2 expression is
      required to prevent the initiation of dying-back pathology at the neuromuscular
      junction in vivo. In contrast, loss of eEF1A2 expression significantly inhibited
      the initiation and progression of Wallerian degeneration in vivo. We conclude
      that loss of eEF1A2 expression distinguishes mechanisms underlying dying-back
      pathology from those responsible for Wallerian degeneration in vivo and suggest
      that eEF1A2-dependent cascades may provide novel molecular targets to manipulate
      neurodegenerative pathways in lower motor neurons.

PMID- 19094182
TI  - Facial asymmetry in young healthy subjects evaluated by statistical shape
      analysis.
AB  - Statistical shape analysis, a relatively a new method for biological research,
      compares body forms by using specific landmarks determined by anatomical
      prominences. In this study, we aimed to identify normal facial asymmetry between
      the right and the left sides of the face. Facial landmark data were collected
      from two-dimensional digital images of 321 young healthy subjects (150 males and
      171 females). These data were analysed using Euclidean distance matrix analysis.
      The number of significantly asymmetric linear distances between the two halves of
      the face was greater in females than in males. We found that the left side of the
      face was most commonly dominant in both males and females. Such data may be
      useful in establishing a database for future similar studies.

PMID- 19094181
TI  - Short-faced mice and developmental interactions between the brain and the face.
AB  - The length of the face represents an important axis of variation in mammals and
      especially in primates. Mice with mutations that produce variation along this
      axis present an opportunity to study the developmental factors that may underlie
      evolutionary change in facial length. The Crf4 mutant, obtained from the C57BL/6J
      (wt/wt) background by chemical mutagenesis by the Baylor Mouse Mutagenesis
      Resource, is reported to have a short-faced phenotype. As an initial step towards
      developing this model, we performed 3D geometric morphometric comparisons of Crf4
      mice to C57BL/6J wild-type mice focusing on three stages of face development and
      morphology--embryonic (GD 9.5-12), neonatal, and adult. Morphometric analysis of
      adult Crf4 mutants revealed that in addition to a shortened face, these mice
      exhibit a significant reduction in brain size and basicranial length. These same
      features also differ at the neonatal stage. During embryonic face formation, only
      dimensions related to brain growth were smaller, whereas the Crf4 face actually
      appeared advanced relative to the wild-type at the same somite stage. These
      results show that aspects of the Crf4 phenotype are evident as early as embryonic
      face formation. Based on our anatomical findings we hypothesize that the
      reduction in facial growth in Crf4 mice is a secondary consequence of reduction
      in the growth of the brain. If correct, the Crf4 mutant will be a useful model
      for studying the role of epigenetic interactions between the brain and face in
      the evolutionary developmental biology of the mammalian craniofacial complex as
      well as human craniofacial dysmorphology.

PMID- 19094183
TI  - Hominid mandibular corpus shape variation and its utility for recognizing species
      diversity within fossil Homo.
AB  - Mandibular corpora are well represented in the hominin fossil record, yet few
      studies have rigorously assessed the utility of mandibular corpus morphology for
      species recognition, particularly with respect to the linear dimensions that are
      most commonly available. In this study, we explored the extent to which commonly
      preserved mandibular corpus morphology can be used to: (i) discriminate among
      extant hominid taxa and (ii) support species designations among fossil specimens
      assigned to the genus Homo. In the first part of the study, discriminant analysis
      was used to test for significant differences in mandibular corpus shape at
      different taxonomic levels (genus, species and subspecies) among extant hominid
      taxa (i.e. Homo, Pan, Gorilla, Pongo). In the second part of the study, we
      examined shape variation among fossil mandibles assigned to Homo (including H.
      habilis sensu stricto, H. rudolfensis, early African H. erectus/H. ergaster, late
      African H. erectus, Asian H. erectus, H. heidelbergensis, H. neanderthalensis and
      H. sapiens). A novel randomization procedure designed for small samples (and
      using group 'distinctness values') was used to determine whether shape variation
      among the fossils is consistent with conventional taxonomy (or alternatively,
      whether a priori taxonomic groupings are completely random with respect to
      mandibular morphology). The randomization of 'distinctness values' was also used
      on the extant samples to assess the ability of the test to recognize known taxa.
      The discriminant analysis results demonstrated that, even for a relatively modest
      set of traditional mandibular corpus measurements, we can detect significant
      differences among extant hominids at the genus and species levels, and, in some
      cases, also at the subspecies level. Although the randomization of 'distinctness
      values' test is more conservative than discriminant analysis (based on
      comparisons with extant specimens), we were able to detect at least four distinct
      groups among the fossil specimens (i.e. H. sapiens, H. heidelbergensis, Asian H.
      erectus and a combined 'African Homo' group consisting of H. habilis sensu
      stricto, H. rudolfensis, early African H. erectus/H. ergaster and late African H.
      erectus). These four groups appear to be distinct at a level similar to, or
      greater than, that of modern hominid species. In addition, the mandibular corpora
      of H. neanderthalensis could be distinguished from those of 'African Homo',
      although not from those of H. sapiens, H. heidelbergensis, or the Asian H.
      erectus group. The results suggest that the features most commonly preserved on
      the hominin mandibular corpus have some taxonomic utility, although they are
      unlikely to be useful in generating a reliable alpha taxonomy for early African
      members of the genus Homo.

PMID- 19094184
TI  - Petrosal anatomy in the fossil mammal Necrolestes: evidence for metatherian
      affinities and comparisons with the extant marsupial mole.
AB  - We present reconstructions of petrosal anatomy based on high-resolution X-ray
      computed tomography scans for the fossil mammal Necrolestes and for the marsupial
      mole Notoryctes sp. Compared with other mammals, Necrolestes exhibits a mosaic of
      plesiomorphic and derived characters, but most of the evidence supports its
      metatherian status. We revised previous descriptions and report on features of
      phylogenetic or functional significance. Necrolestes exhibits features that
      support metatherian affinities, such as the presence of a short and lateral
      prootic canal, and the loss of the stapedial artery in adults. A deep groove at
      the anterior pole of the promontorium is present in front of the cochlear
      housing, a variant on the extrabullar pathway of the internal carotid artery. The
      promontorium is laterally bordered by a large bony projection resembling the
      eutherian tegmen tympani [De Beer GR (1937) The Development of the Vertebrate
      Skull, Oxford, Clarendon Press, p. 391]. Posteromedial to the secondary facial
      foramen and anterolateral to the fenestra vestibuli is a pronounced fossa for the
      tensor tympani muscle. On the medial part of the pars canalicularis there is a
      great inflation of the medial side of the caudal tympanic process, a structure of
      unknown function. The internal acoustic meatus exhibits a broad transverse septum
      and is bordered laterally by a broad prefacial commissure. The cochleae of
      Necrolestes and of Notoryctes have fewer spiral turns (1.1 and 1.6, respectively)
      than most marsupials. The lateral semicircular canal is more expanded than the
      posterior semicircular canal in Necrolestes but not in Notoryctes. Both
      Necrolestes and Notoryctes have a second crus commune, i.e. the lateral
      semicircular canal opens into the ampulla of the posterior semicircular canal. A
      stylomastoid foramen enclosed anterodorsally by both the pars cochlearis and pars
      canalicularis is present in Dasyuridae, Dromiciops gliroides and Notoryctes.

PMID- 19094185
TI  - A three-dimensional microcomputed tomographic study of site-specific variation in
      trabecular microarchitecture in the human second metacarpal.
AB  - Variation in trabecular microarchitecture is widely accepted as being regulated
      by both functional (mechanical loading) and genetic parameters, although the
      relative influence of each is unclear. Studies reporting inter-site differences
      in trabecular morphology (volume, number and structure) reveal a complex
      interaction at the gene-environment interface. We report inter- and intra-site
      variation in trabecular anatomy using a novel model of contralateral (left vs
      right) and ipsilateral (head vs base) comparisons for the human second metacarpal
      in a sample of n = 29 historically known 19th century EuroCanadians. Measures of
      bone volume fraction, structure model index, connectivity, trabecular number,
      spacing and thickness as well as degree of anisotropy were obtained from 5-mm
      volumes of interest using three-dimensional microcomputed tomography. We
      hypothesized that: (i) the more diverse loading environment of metacarpal heads
      should produce a more robust trabecular architecture than corresponding bases
      within sides and (ii) the ipsilateral differences between epiphyses will be
      larger on the right side than on the left side, as a function of handedness.
      Analysis of covariance (Side x Epiphysis) with Age as covariate revealed a clear
      dichotomy between labile and constrained architectures within and among
      anatomical sites. The predicted variation in loading was accommodated by changes
      in trabecular volume, whereas trabecular structure did not vary significantly by
      side or by epiphysis within sides. Age was a significant covariate only for
      females. We conclude that environmental and genetic regulation of bone adaptation
      may act through distinct pathways and local anatomies to ensure an integrated
      lattice of sufficient mass to meet normal functional demands.

PMID- 19094186
TI  - Exercise-induced metacarpophalangeal joint adaptation in the Thoroughbred
      racehorse.
AB  - Repetitive bone injury and development of stress fracture is a common problem in
      humans and animals. The Thoroughbred racehorse is a model in which adaptive
      failure and associated development of stress fracture is common. We performed a
      histologic study of the distal end of the third metacarpal bone in two groups of
      horses: young Thoroughbreds that were actively racing (n = 10) and a group of non
      athletic horses (n = 8). The purpose of this study was to determine whether
      development of articular microcracks was associated with specific alterations to
      subchondral plate osteocytes. Morphometric measurements were made in five regions
      of the joint surface: lateral condyle, lateral condylar groove, sagittal ridge,
      medial condylar groove, and medial condyle. The following variables were
      quantified: hyaline cartilage width; calcified cartilage width; the number of
      tidemarks; microcrack density at the articular surface; blood vessel density
      entering articular cartilage; the presence of atypical bone matrix in the
      subchondral plate; bone volume fraction; and osteocyte density. Adaptation of
      articular cartilage was similar in both groups of horses. Vascularization of
      articular cartilage was increased in the group of non-athletic horses.
      Microcracks, which typically had an oblique orientation to the joint surface,
      were co-localized with blood vessels, and resorption spaces. Microcracking was
      increased in the condylar grooves of athletic horses compared with the other
      joint regions and was also increased compared with the condylar groove regions of
      non-athletic horses. Coalescence of microcracks also led to development of an
      intracortical articular condylar stress fracture in some joints and targeted
      remodeling of affected subchondral plate. The subchondral plate of the condyles
      in athletic horses was sclerotic, and contained atypically stained bone matrix
      with increased numbers of osteocytes with atypical morphology. However, osteocyte
      numbers were not significantly different between groups. We conclude that
      differences in site-specific microdamage accumulation and associated targeted
      remodeling between athletic and non-athletic horses are much greater than
      differences in subchondral osteocyte morphology. However, the presence of
      atypical subchondral bone matrix in athletic horses was associated with extensive
      osteocyte loss. Although osteocyte mechanotransduction is considered important
      for functional adaptation, in this model, adaptation is likely regulated by
      multiple mechanotransduction pathways.

PMID- 19094187
TI  - Development of the human Achilles tendon enthesis organ.
AB  - The attachment of the Achilles tendon is part of an 'enthesis organ' that reduces
      stress concentration at the hard-soft tissue interface. The organ also includes
      opposing sesamoid and periosteal fibrocartilages, a bursa and Kager's fat pad. In
      addition, the deep crural and plantar fasciae contribute to Achilles stress
      dissipation and could also be regarded as components. Here we describe the
      sequence in which these various tissues differentiate. Serial sections of feet
      from spontaneously aborted foetuses (crown rump lengths 22-322 mm) were examined.
      All slides formed part of an existing collection of histologically sectioned
      embryological material, obtained under Spanish law and housed in the Universidad
      Complutense, Madrid. From the earliest stages, it was evident that the Achilles
      tendon and plantar fascia had a mutual attachment to the calcaneal perichondrium.
      The first components of the enthesis organ to appear (in the 45-mm foetus) were
      the retrocalcaneal bursa and the crural fascia. The former developed by
      cavitation within the mesenchyme that later gave rise to Kager's fat pad. The tip
      of the putative fat pad protruded into the developing bursa in the 110-mm foetus
      and fully differentiated adipocytes were apparent in the 17-mm foetus. All three
      fibrocartilages were first recognisable in the 332-mm foetus--at which time
      adipogenesis had commenced in the heel fat pad. The sequence in which the various
      elements became apparent suggests that bursal formation and the appearance of the
      crural fascia may be necessary to facilitate the foot movements that subsequently
      lead to fibrocartilage differentiation. The later commencement of adipogenesis in
      the heel than in Kager's pad probably reflects the non-weight environment in
      utero. The direct continuity between plantar fascia and Achilles tendon that is
      characteristic of the adult reflects the initial attachment of both structures to
      the calcaneal perichondrium rather than to the skeletal anlagen itself.

PMID- 19094188
TI  - Zonal variations in cytoskeletal element organization, mRNA and protein
      expression in the intervertebral disc.
AB  - The intervertebral disc is important in maintaining flexibility and dissipating
      loads applied to the spine. The disc comprises a heterogeneous population of
      cells, including those of the nucleus pulposus and annulus fibrosus, which are
      diverse in phenotype, partly due to the different mechanical loads they
      experience. Several studies have implicated the cytoskeleton in
      mechanotransduction, but little characterization of the three major cytoskeletal
      elements--actin, tubulin and vimentin--in the intervertebral disc has been
      undertaken. In this study we show that there are differences in both the
      organization and the amounts of these cytoskeletal proteins across the regions of
      immature bovine intervertebral disc (nucleus pulposus and outer annulus
      fibrosus), which differs with skeletal maturity. These differences are likely to
      reflect the diverse mechanical characteristics of the disc regions, and the loads
      that they experience, i.e. tension in the annulus fibrosus and compression in the
      nucleus pulposus. Alterations to the organization and amount of cytoskeletal
      element proteins may change the ability of the cells to respond to mechanical
      signals, with a loss of tissue homeostasis, suggesting that the cytoskeleton has
      a potential role in intervertebral disc degeneration.

PMID- 19094189
TI  - Morphology of deltoid origin and end tendons--a generic model.
AB  - This study provides a model of the complex deltoid origin and end tendons, as a
      basis for further anatomical, biomechanical and clinical research. Although the
      deltoid is used in transpositions with upper limb paralysis, its detailed
      morphology and segmentation has not been object of much study. Morphologically,
      the deltoid faces two distinct challenges. It closely envelops a ball joint, and
      it reduces its width over a short distance from a very wide origin along
      clavicle, acromion and spina scapula, to an insertion as narrow as the humerus.
      These challenges necessitate specific morphological tendon adaptations. A
      qualitative model for these tendons is developed by the stepwise transformation
      of a unipennate muscle model into a functional deltoid muscle. Each step is the
      solution to one of the mentioned morphological challenges. The final model is of
      an end tendon consisting of a continuous succession of bipennate end tendon
      blades centrally interspaced by unipennate tendon parts. The origin tendon
      consists of lamellae that interdigitate with the end tendon blades, creating a
      natural segmentation. The model is illustrated by qualitative dissection results.
      In addition, in view of a proliferation of terms found in the literature to
      describe deltoid tendons, tendon concepts are reviewed and the systematic use of
      the unique and simple terminology of 'origin and end tendons' is proposed.

PMID- 19094190
TI  - Regional differences in fiber characteristics in the rat temporalis muscle.
AB  - The behavioral differences in muscle use are related to the fiber type
      composition of the muscles among other variables. The aim of this study was to
      examine the degree of heterogeneity in the fiber type composition in the rat
      temporalis muscle. The temporalis muscle was taken from 10-week-old Wistar strain
      male rats (n = 5). Fiber types were classified by immunohistochemical staining
      according to their myosin heavy chain content. The anterior temporalis revealed
      an obvious regional difference of the fiber type distribution, whereas the
      posterior temporalis was homogeneous. The deep anterior temporalis showed a
      predominant proportion of type IIA fibers and was the only muscle portion
      displaying slow type fibers (< 10%). The other two muscle portions, the
      superficial anterior and posterior temporalis, did not differ significantly from
      each other and contained mainly type IIB fibers. Moreover, the deep anterior
      temporalis was the only muscle portion showing slow type fibers (< 10%). In the
      deep portion, type IIX fibers revealed the largest cross-sectional area (1943.1
      +/- 613.7 microm(2)), which was significantly (P < 0.01) larger than those of
      type IIA and I + IIA fibers. The cross-sectional area of type IIB fibers was the
      largest in the remaining two muscle portions and was significantly (P < 0.01)
      larger than that of type IIX fibers. In conclusion, temporalis muscle in rats
      showed an obvious heterogeneity of fiber type composition and fiber cross
      sectional area, which suggests multiple functions of this muscle.

PMID- 19094191
TI  - The role of human beta-defensin-2 in bone.
AB  - Osteomyelitis often causes functional impairment due to tissue destruction. This
      report demonstrates a novel previously unappreciated role of osteoblasts. Samples
      of osteomyelitic bone and bacterially challenged osteoblasts produce increased
      amounts of antimicrobial peptides in order to combat bacterial bone infection. An
      osteomyelitis mouse model confirmed the osseous induction of the murine homologue
      of human beta-defensin-2, suggesting a central role in the prevention of
      bacterial bone infection. Antimicrobial peptides are effectors of the innate
      defence system and play a key role in host protection at cellular surfaces. Some
      of them are produced constitutively, whereas others are induced during infection.
      Human beta-defensins represent a major subclass of antimicrobial peptides and act
      as a first line of defence through their broad spectrum of potent antimicrobial
      activity. The aim of the present in-vitro and in-vivo investigations was to study
      the expression and regulation of human beta-defensin-2 in the case of bacterial
      bone infection and to analyse the effects of immunosuppressive drugs on bone
      derived antimicrobial peptide expression. Samples of healthy human bone,
      osteomyelitic bone and cultured osteoblasts (hFOB cells) were assessed for the
      expression of human beta-defensin-2. Regulation of human beta-defensin-2 was
      studied in hFOB cells after exposure to bacterial supernatants, proinflammatory
      cytokines and immunosuppressive drugs (glucocorticoids and methotrexate) and was
      assayed by enzyme-linked immunosorbent assay. An osteomyelitis mouse model was
      performed to demonstrate the regulation of the murine homologue of human beta
      defensin-2, named murine beta-defensin-3, by real-time reverse transcription
      polymerase chain reaction and immunohistochemistry. Healthy human bone and
      cultured osteoblasts are able to produce human beta-defensin-2 under standard
      conditions. Samples of infected bone produce higher levels of endogenous
      antibiotics, such as human beta-defensin-2, when compared with samples of healthy
      bone. A clear induction of human beta-defensin-2 was observed after exposure of
      cultured osteoblasts to gram-positive bacteria or proinflammatory cytokines.
      Additional treatment with glucocorticoids or methotrexate prevented bacteria
      mediated antimicrobial peptide induction in cultured osteoblasts. The
      osteomyelitis mouse model demonstrated transcriptional upregulation of the murine
      homologue of human beta-defensin-2, namely murine beta-defensin-3, in bone after
      intraosseous contamination of the tibia. Human and murine bone have the ability
      to produce broad-spectrum endogenous antibiotics when challenged by micro
      organisms in vitro and in vivo. Immunosuppressive drugs, such as glucocorticoids
      or methotrexate, may increase the susceptibility to bone infection by decreasing
      antimicrobial peptide expression levels in case of microbial challenge. The
      induction of human beta-defensin-2 following bacterial contact suggests a central
      role of antimicrobial peptides in the prevention of bacterial bone infection.

PMID- 19094192
TI  - Abrupt termination of an ethanol regimen provokes ventricular arrhythmia and
      enhances susceptibility to the arrhythmogenic effects of epinephrine in rats.
AB  - BACKGROUND: Pathologists examining victims of sudden unexpected death encounter
      alcoholics more often than expected; alcohol may play a role in sudden arrhythmic
      death. Here we determine whether a pattern of alcohol consumption, chronic
      ethanol intake, and withdrawal increases the incidence of malignant ventricular
      arrhythmia and modulates susceptibility to the arrhythmogenic potential of
      sympathetic stimulation from an epinephrine test in rats. METHODS: Male Wistar
      rats were treated with a continuous ethanol liquid diet for 7 weeks, and then
      subjected to 1-day withdrawal or 21-day abstinence. Ventricular ectopy was
      evaluated by 24-hour electrocardiographic telemetry recording; whole-body
      sympathetic activation, cardiac sympathovagal balance, and susceptibility to
      ventricular arrhythmia induced by sympathetic stimulation were evaluated based on
      blood noradrenalin metabolite concentrations, heart rate variability, and a 3
      step epinephrine test. RESULTS: Ventricular arrhythmia and related death were
      observed only in rats at 1 day of withdrawal, but not in nonalcoholic, continuous
      ethanol intake or 21-day abstinence rats. One-day withdrawal after a 7-week
      continuous ethanol regimen elevated circulating noradrenalin metabolite levels
      and induced cardiac sympathovagal imbalance. Deaths related to the epinephrine
      test and ventricular arrhythmia induced by low doses of epinephrine were observed
      only in 1-day withdrawal rats. However, all anomalies were normalized by 21-day
      abstinence. CONCLUSIONS: Abrupt termination of a 7-week continuous ethanol
      regimen is sufficient to enhance the whole-body sympathetic activation and
      cardiac sympathovagal imbalance that contribute to ventricular arrhythmia and
      sudden death in alcoholic rats. Those providing medical care for alcoholics,
      including in cases of legal imprisonment, should be aware of the possibility of
      enhanced susceptibility to sudden arrhythmic death due to the abrupt termination
      of a chronic ethanol regimen.

PMID- 19094193
TI  - Potential role of enhanced cytokinemia and plasma inhibitor on the decreased
      activity of plasma ADAMTS13 in patients with alcoholic hepatitis: relationship to
      endotoxemia.
AB  - BACKGROUND: Deficiency of ADAMTS13 (adisintegrin-like and metalloproteinase with
      thrombospondin type-1 motifs 13) results in an increase in unusually large von
      Willebrand factor multimer (UL-VWFM) of the plasma and finally causes
      microcirculatory disturbance. Our previous study demonstrated that the imbalance
      of increased UL-VWFM over decreased ADAMTS13 activity may contribute to the
      development of multiorgan failure in patients with alcoholic hepatitis (AH). The
      aim of this study was to explore the potential mechanism to reduce the activity
      of plasma ADAMTS13. METHODS: Plasma cytokine levels including interleukin (IL)-6,
      IL-8, and tumor necrosis factor-alpha (TNF-alpha), plasma endotoxin
      concentration, and the plasma inhibitor against ADAMTS13 were determined together
      with ADAMTS13 activity, VWF antigen (VWF:Ag), and UL-VWFM in 24 patients with AH
      and 5 patients with severe alcoholic hepatitis (SAH). RESULTS: The concentrations
      of IL-6, IL-8, and TNF-alpha on admission were significantly higher in patients
      with SAH than in those with AH and controls. The ADAMTS13 activity concomitantly
      decreased, and the VWF:Ag progressively elevated with increasing concentrations
      of these cytokines from normal range to over 100 pg/ml. Plasma endotoxin
      concentration was markedly higher in patients with SAH (mean 52.3 pg/ml) and AH
      (21.7 pg/ml) than in controls (7.9 pg/ml). The endotoxin concentration inversely
      correlated with ADAMTS13 activity and was higher in patients with UL-VWFM than
      those without. The inhibitor was detected in 4 patients with SAH (0.9 to 2.1
      BU/ml) and 6 patients with AH (0.5 to 1.6 BU/ml). Patients with the inhibitor
      showed lower functional liver capacity, higher endotoxin concentration, and
      marked inflammatory signs than those without. At the recovery stage, the ADAMTS13
      activity increased to normal range, the VWF:Ag decreased, and the UL-VWFM
      disappeared with the decrease in the concentrations of cytokines and endotoxin,
      and the disappearance of the inhibitor. CONCLUSION: Decreased ADAMTS13 activity
      and increased VWF:Ag could be induced not only by pro-inflammatory cytokinemia,
      but also by its inhibitor, both of which may be closely related to enhanced
      endotoxemia in patients with AH and SAH.

PMID- 19094194
TI  - Planning ahead in public health? A qualitative study of the time horizons used in
      public health decision-making.
AB  - BACKGROUND: In order to better understand factors that influence decisions for
      public health, we undertook a qualitative study to explore issues relating to the
      time horizons used in decision-making. METHODS: Qualitative study using semi
      structured interviews. 33 individuals involved in the decision making process
      around coronary heart disease were purposively sampled from the UK National
      Health Service (national, regional and local levels), academia and voluntary
      organizations. Analysis was based on the framework method using N-VIVO software.
      Interviews were transcribed, coded and emergent themes identified. RESULTS: Many
      participants suggested that the timescales for public health decision-making are
      too short. Commissioners and some practitioners working at the national level
      particularly felt constrained in terms of planning for the long-term. Furthermore
      respondents felt that longer term planning was needed to address the wider
      determinants of health and to achieve societal level changes. Three prominent
      'systems' issues were identified as important drivers of short term thinking: the
      need to demonstrate impact within the 4 year political cycle; the requirement to
      'balance the books' within the annual commissioning cycle and the disruption
      caused by frequent re-organisations within the health service. In addition
      respondents suggested that the tools and evidence base for longer term planning
      were not well established. CONCLUSION: Many public health decision and policy
      makers feel that the timescales for decision-making are too short. Substantial
      systemic barriers to longer-term planning exist. Policy makers need to look
      beyond short-term targets and budget cycles to secure investment for long-term
      improvement in public health.

PMID- 19094195
TI  - Assessment of codivergence of mastreviruses with their plant hosts.
AB  - BACKGROUND: Viruses that have spent most of their evolutionary time associated
      with a single host lineage should have sequences that reflect codivergence of
      virus and host. Several examples for RNA viruses of host-virus tree congruence
      are being challenged. DNA viruses, such as mastreviruses, are more likely than
      RNA viruses to have maintained a record of host lineage association. RESULTS: The
      full genomes of 28 isolates of Wheat dwarf virus (WDV), a member of the
      Mastrevirus genus, from different regions of China were sequenced. The analysis
      of these 28 entire genomes and 18 entire genome sequences of cereal mastreviruses
      from other countries support the designation of wheat, barley and oat mastrevirus
      isolates as separate species. They revealed that relative divergence times for
      the viruses WDV, Barley dwarf virus (BDV), Oat dwarf virus (ODV) and Maize streak
      virus (MSV) are proportional to divergence times of their hosts, suggesting
      codivergence. Considerable diversity among Chinese isolates was found and was
      concentrated in hot spots in the Rep A, SIR, LIR, and intron regions in WDV
      genomes. Two probable recombination events were detected in Chinese WDV isolates.
      Analysis including further Mastrevirus genomes concentrated on coding regions to
      avoid difficulties due to recombination and hyperdiversity. The analysis
      demonstrated congruence of trees in two branches of the genus, but not in the
      third. Assuming codivergence, an evolutionary rate of 10-8 substitutions per site
      per year was calculated. The low rate implies stronger constraints against change
      than are obtained by other methods of estimating the rate. CONCLUSION: We report
      tests of the hypothesis that mastreviruses have codiverged with their
      monocotyledonous hosts over 50 million years of evolution. The tests support the
      hypothesis for WDV, BDV and ODV, but not for MSV and other African streak
      viruses.

PMID- 19094196
TI  - Combined myocardial stress perfusion imaging and myocardial stress tagging for
      detection of coronary artery disease at 3 Tesla.
AB  - BACKGROUND: Adenosine stress perfusion is very sensitive for detection of
      coronary artery disease (CAD), and yields good specificity. Standard adenosine
      cine imaging lacks high sensitivity, but is very specific. Myocardial tagging
      improves detection of wall motion abnormalities (WMAs). Perfusion and tagging
      cardiovascular magnetic resonance (CMR) both benefit from high field imaging
      (improved contrast to noise ratio and tag persistence). We investigated the
      diagnostic impact of a combined stress perfusion-tagging protocol for detection
      of CAD at 3 Tesla. METHODS: Stress perfusion and tagging images were acquired in
      3 identical short axis locations (slice thickness 8 mm, FOV 320-380 mm, matrix
      256(2)). A positive finding at coronary angiography was defined as stenosis or
      flow limiting restenosis > 50% in native and graft vessels. A true positive CMR -
      finding was defined as > or = 1 perfusion deficit or new WMA during adenosine
      stress in angiographically corresponding regions. RESULTS: We included 60
      patients (males: 41, females: 19; 21 suspected, 39 known CAD). Myocardial tagging
      extended stress imaging by 1.5-3 min and was well tolerated by all patients.
      Sensitivity and specificity for detection of significant CAD by adenosine stress
      perfusion were 0.93 and 0.84, respectively. The sensitivity of adenosine stress
      tagging was less (0.64), while the specificity was very high (1.0). The
      combination of both stress perfusion and stress tagging did not increase
      sensitivity. CONCLUSION: The combined adenosine stress perfusion-tagging protocol
      delivers high sensitivity and specificity for detection of significant CAD. While
      the sensitivity of adenosine stress tagging is poor compared to perfusion
      imaging, its specificity is very high. This technique should thus prove useful in
      cases of inconclusive perfusion studies to help avoid false positive results.

PMID- 19094197
TI  - Changes in the total leukocyte and platelet counts in Papuan and non Papuan
      adults from northeast Papua infected with acute Plasmodium vivax or uncomplicated
      Plasmodium falciparum malaria.
AB  - BACKGROUND: There are limited data on the evolution of the leukocyte and platelet
      counts in malaria patients. METHODS: In a clinical trial of chloroquine vs.
      chloroquine plus doxycycline vs. doxycycline alone against Plasmodium vivax (n =
      64) or Plasmodium falciparum (n = 98) malaria, the total white cell (WCC) and
      platelet (PLT) counts were measured on Days 0, 3, 7 and 28 in 57 indigenous
      Papuans with life long malaria exposure and 105 non Papuan immigrants from other
      parts of Indonesia with limited malaria exposure. RESULTS: The mean Day 0 WCC (n
      = 152) was 6.492 (range 2.1-13.4) x 10(9)/L and was significantly lower in the
      Papuans compared to the non Papuans: 5.77 x 10(9)/L vs. 6.86 x 10(9)/L,
      difference = -1.09 [(95% CI -0.42 to -1.79 x 10(9)/L), P = 0.0018]. 14 (9.2%) and
      9 (5.9%) patients had leukopaenia (<4.0 x 10(9)/L) and leukocytosis (>10.0 x
      10(9)/L), respectively. By Day 28, the mean WCC increased significantly (P =
      0.0003) from 6.37 to 7.47 x 10(9)/L (73 paired values) and was similar between
      the two groups. Ethnicity was the only WCC explanatory factor and only on Day
      0.The mean Day 0 platelet count (n = 151) was 113.0 (range 8.0-313.0) x 10(9)/L
      and rose significantly to 186.308 x 10(9)/L by Day 28 (P < 0.0001). There was a
      corresponding fall in patient proportions with thrombocytopaenia (<150 x
      10(9)/L): 119/151 (78.81%) vs. 16/73 (21.92%, P < 0.00001). Papuan and non Papuan
      mean platelet counts were similar at all time points. Only malaria species on Day
      0 was a significant platelet count explanatory factor. The mean D0 platelet
      counts were significantly lower (P = 0.025) in vivax (102.022 x 10(9)/L) vs.
      falciparum (122.125 x 10(9)/L) patients. CONCLUSION: Changes in leukocytes and
      platelets were consistent with other malaria studies. The Papuan non Papuan
      difference in the mean Day 0 WCC was small but might be related to the difference
      in malaria exposure.

PMID- 19094198
TI  - Individual, facility and policy level influences on national coverage estimates
      for intermittent preventive treatment of malaria in pregnancy in Tanzania.
AB  - BACKGROUND: Delivery of two doses of intermittent preventive treatment of malaria
      during pregnancy (IPTp) is a key strategy to reduce the burden of malaria in
      pregnancy in sub-Saharan Africa. However, different settings have reported
      coverage levels well below the target 80%. Antenatal implementation guidelines in
      Tanzania recommend IPTp first dose to be given at the second antenatal visit, and
      second dose at the third visit. This investigation measured coverage of IPTp at
      national level in Tanzania and examined the role of individual, facility, and
      policy level influences on achieved coverage. METHODS: Three national household
      and linked reproductive and child health (RCH) facility surveys were conducted
      July-August 2005, 2006, and 2007 in 210 clusters sampled using two-stage cluster
      sampling from 21 randomly selected districts. Female residents who reported a
      livebirth in the previous year were asked questions about malaria prevention
      during that pregnancy and individual characteristics including education,
      pregnancy history, and marital status. The RCH facility serving each cluster was
      also surveyed, and information collected about drug stocks, health education
      delivery, and the timing of antenatal care delivery by clinic users. RESULTS: The
      national IPTp coverage had declined over the survey period being 71% for first
      dose in 2005 falling to 65% in 2007 (chi2 2.9, p = 0.05), and 38% for second dose
      in 2005 but 30% in 2007 (chi2 4.4, p = 0.01). There was no evidence of any
      individual factors being associated with second dose coverage beyond living in an
      urban area. Availability of sulphadoxine-pyrimethamine at RCH had decreased year
      on year from 85% of clinics in stock in 2005 to 60% in 2007 (chi2 20.6, p <
      0.001). This reduction was evident in rural but not urban clinics. If safety
      recommendations and national antenatal care guidelines for IPTp delivery were
      followed, in 2007 only 76% of pregnant women could have received IPTp first dose
      and only 46% could have received second dose. CONCLUSION: There is scope to
      improve IPTp first and second dose coverage at national scale within existing
      systems by improving stock at RCH, and by revising the existing guidelines to
      recommend delivery of IPTp after quickening, rather than at a pre-defined
      antenatal visit.

PMID- 19094199
TI  - Development of a quality assurance handbook to improve educational courses in
      Africa.
AB  - BACKGROUND: The attainment of the Millennium Development Goals has been hampered
      by the lack of skilled and well-informed health care workers in many developing
      countries. The departure of health care workers from developing countries is one
      of the most important causes. One of the motivations for leaving is that
      developed countries have well-established health care systems that incorporate
      continuing medical education, which enables health care workers to develop their
      skills and knowledge base. This provision is lacking in many developing
      countries. The provision of higher-education programmes of good quality within
      developing countries therefore, contributes to building capacity of the health
      care workforce in these countries. METHODS: The Liverpool School of Tropical
      Medicine is involved in delivering off-site higher educational programmes to
      health care workers in Africa. Our colleagues at one of these sites requested a
      guide to help them ensure that their professional development courses met
      international educational standards. We reviewed published literature that
      outlines the principles of quality assurance in higher education from various
      institutions worldwide. Using this information, we designed a handbook that
      outlines the quality assurance principles in a simple and practical way. This was
      intended to enable institutions, even in developing countries, to adapt these
      principles in accordance with their local resource capacity. We subsequently
      piloted this handbook at one of the sites in Ghana. The feedback from this aided
      the development of the handbook. The development of this handbook was
      participatory in nature. RESULTS: The handbook addresses six main themes that are
      the minimum requirements that a higher education course should incorporate to
      ensure that it meets internationally recognized standards. These include:
      recruitment and admissions, course design and delivery, student assessments,
      approval and review processes, support for students and staff training and
      welfare. It has been piloted in Ghana and the feedback was incorporated into the
      handbook. The handbook is currently available free of charge online and being
      used by various institutions across the world. We have had responses from
      individuals and institutions in Africa, Asia, North America and Europe.
      CONCLUSION: The principles outlined in the handbook provide a regulatory
      framework for locally establishing higher education courses of good quality that
      will contribute to enhancing the teaching and learning experience of students in
      courses in the developing world. This would contribute to providing a skilled and
      sustainable health care workforce that would reduce the need for health care
      workers to travel overseas in search of good higher education courses.

PMID- 19094200
TI  - Genetic variation in the catechol-O-methyltransferase (COMT) gene and morphine
      requirements in cancer patients with pain.
AB  - BACKGROUND: Genetic variation contributes to differences in pain sensitivity and
      response to different analgesics. Catecholamines are involved in the modulation
      of pain and are partly metabolized by the catechol-O-methyltransferase (COMT)
      enzyme. Genetic variability in the COMT gene may therefore contribute to
      differences in pain sensitivity and response to analgesics. It is shown that a
      polymorphism in the COMT gene, Rs4680 (Val158Met), influence pain sensitivity in
      human experimental pain and the efficacy for morphine in cancer pain treatment.
      In this study we wanted to investigate if variability in other regions in the
      COMT gene also contributes to interindividual variability in morphine efficacy.
      RESULTS: We genotyped 11 single nucleotide polymorphisms (SNPs) throughout the
      COMT gene, and constructed haplotypes from these 11 SNPs, which were in Hardy
      Weinberg equilibrium. We compared both genotypes and haplotypes against
      pharmacological, demographical and patient symptoms measurements in a Caucasian
      cancer patient cohort (n = 197) receiving oral morphine treatment for cancer
      pain. There were two frequent haplotypes (34.5% and 17.8%) in our cohort.
      Multivariate analyses showed that patients carrying the most frequent haplotype
      (34.5%) needed lower morphine doses than patients not carrying the haplotype,
      with a reduction factor of 0.71 (p = 0.005). On the allele level, carriers of
      alleles for six of the SNPs show weak associations in respect to morphine dose
      and the alleles associated with the lowest morphine doses constitute part of the
      most frequent haplotype. CONCLUSION: This study suggests that genetic variability
      in the COMT gene influence the efficacy of morphine in cancer patients with pain,
      and that increased understanding of this variability is reached by expanding from
      analyses of single SNPs to haplotype construction and analyses.

PMID- 19094201
TI  - Health challenges in Africa and the way forward.
AB  - Africa is confronted by a heavy burden of communicable and non-communicable
      diseases. Cost-effective interventions that can prevent the disease burden exist
      but coverage is too low due to health systems weaknesses. This editorial reviews
      the challenges related to leadership and governance; health workforce; medical
      products, vaccines and technologies; information; financing; and services
      delivery. It also provides an overview of the orientations provided by the WHO
      Regional Committee for Africa for overcoming those challenges. It cautions that
      it might not be possible to adequately implement those orientations without a
      concerted fight against corruption, sustained domestic and external investment in
      social sectors, and enabling macroeconomic and political (i.e. internally secure)
      environment.

PMID- 19094202
TI  - Enhanced external counter pulsation in treatment of refractory angina pectoris:
      two year outcome and baseline factors associated with treatment failure.
AB  - BACKGROUND: Enhanced external counter pulsation (EECP) is a non-invasive
      treatment option for patients with refractory angina pectoris ineligible to
      further traditional treatment. The aim of this study was to evaluate the effect
      of EECP on patients at a Scandinavian medical centre and to investigate if
      outcome can be predicted by analysing baseline factors. METHODS: 86 consecutive
      patients (70 male, 16 female) were treated with EECP and followed for two years
      post treatment. Canadian cardiovascular society (CCS) class was analysed, and
      medication and adverse clinical events were researched prior to EECP, at the end
      of the treatment, and at six, 12 and 24 months thereafter. Patients responding to
      therapy by improving at least one CCS class were compared with those who failed
      to respond. Any differences in background factors were recorded and analysed.
      RESULTS: 79% of the patients responded to therapy by improving at least one CCS
      class. In general, the CCS class improved by one class after EECP treatment (3.05
      before versus 2.14 after treatment). A total of 61.5% of the initial responders
      showed sustained improvement at the 12 month follow-up while 29% presented
      sustained improvement after 24 months. Treatment was most effective among
      patients suffering from CCS class III-IV angina pectoris, while patients
      suffering from CCS class II angina pectoris improved transiently but failed to
      show sustained improvement after the 12 month follow-up. Diabetes mellitus and
      calcium channel antagonists were more common among the non-responders (p < 0.05).
      CONCLUSION: This study confirms the safety and efficiency of EECP as a treatment
      option for patients suffering from refractory angina pectoris. The therapy is
      most beneficial in patients suffering from severe angina (CCS III-IV) while
      sustained response to therapy could not be verified among patients suffering from
      CCS class II angina pectoris.

PMID- 19094203
TI  - Mannose binding lectin plays a crucial role in innate immunity against yeast by
      enhanced complement activation and enhanced uptake of polymorphonuclear cells.
AB  - BACKGROUND: Mannose binding lectin (MBL) is an important host defence protein
      against opportunistic fungal pathogens. This carbohydrate-binding protein, an
      opsonin and lectin pathway activator, binds through multiple lectin domains to
      the repeating sugar arrays displayed on the surface of a wide range of clinically
      relevant microbial species. We investigated the contribution of MBL to antifungal
      innate immunity towards C. parapsilosis in vitro. RESULTS: High avidity binding
      was observed between MBL and C. albicans and C. parapsilosis. Addition of MBL to
      MBL deficient serum increased the deposition of C4 and C3b and enhanced the
      uptake of C. albicans, C. parapsilosis and acapsular C. neoformans by
      polymorphonuclear cells (PMNs). Compared to other microorganisms, such as
      Escherichia coli, Staphylococcus aureus and Cryptococcus neoformans, C.
      parapsilosis and Candida albicans were potent activators of the lectin pathway.
      CONCLUSION: Our results suggest that MBL plays a crucial role in the innate
      immunity against infections caused by yeast by increasing uptake by PMN.

PMID- 19094206
TI  - Prediction of regulatory elements in mammalian genomes using chromatin
      signatures.
AB  - BACKGROUND: Recent genomic scale survey of epigenetic states in the mammalian
      genomes has shown that promoters and enhancers are correlated with distinct
      chromatin signatures, providing a pragmatic way for systematic mapping of these
      regulatory elements in the genome. With rapid accumulation of chromatin
      modification profiles in the genome of various organisms and cell types, this
      chromatin based approach promises to uncover many new regulatory elements, but
      computational methods to effectively extract information from these datasets are
      still limited. RESULTS: We present here a supervised learning method to predict
      promoters and enhancers based on their unique chromatin modification signatures.
      We trained Hidden Markov models (HMMs) on the histone modification data for known
      promoters and enhancers, and then used the trained HMMs to identify promoter or
      enhancer like sequences in the human genome. Using a simulated annealing (SA)
      procedure, we searched for the most informative combination and the optimal
      window size of histone marks. CONCLUSION: Compared with the previous methods, the
      HMM method can capture the complex patterns of histone modifications particularly
      from the weak signals. Cross validation and scanning the ENCODE regions showed
      that our method outperforms the previous profile-based method in mapping
      promoters and enhancers. We also showed that including more histone marks can
      further boost the performance of our method. This observation suggests that the
      HMM is robust and is capable of integrating information from multiple histone
      marks. To further demonstrate the usefulness of our method, we applied it to
      analyzing genome wide ChIP-Seq data in three mouse cell lines and correctly
      predicted active and inactive promoters with positive predictive values of more
      than 80%. The software is available at
      http://http:/nash.ucsd.edu/chromatin.tar.gz.

PMID- 19094205
TI  - The fate of the duplicated androgen receptor in fishes: a late
      neofunctionalization event?
AB  - BACKGROUND: Based on the observation of an increased number of paralogous genes
      in teleost fishes compared with other vertebrates and on the conserved synteny
      between duplicated copies, it has been shown that a whole genome duplication
      (WGD) occurred during the evolution of Actinopterygian fish. Comparative
      phylogenetic dating of this duplication event suggests that it occurred early on,
      specifically in teleosts. It has been proposed that this event might have
      facilitated the evolutionary radiation and the phenotypic diversification of the
      teleost fish, notably by allowing the sub- or neo-functionalization of many
      duplicated genes. RESULTS: In this paper, we studied in a wide range of
      Actinopterygians the duplication and fate of the androgen receptor (AR, NR3C4), a
      nuclear receptor known to play a key role in sex-determination in vertebrates.
      The pattern of AR gene duplication is consistent with an early WGD event: it has
      been duplicated into two genes AR-A and AR-B after the split of the
      Acipenseriformes from the lineage leading to teleost fish but before the
      divergence of Osteoglossiformes. Genomic and syntenic analyses in addition to
      lack of PCR amplification show that one of the duplicated copies, AR-B, was lost
      in several basal Clupeocephala such as Cypriniformes (including the model species
      zebrafish), Siluriformes, Characiformes and Salmoniformes. Interestingly, we also
      found that, in basal teleost fish (Osteoglossiformes and Anguilliformes), the two
      copies remain very similar, whereas, specifically in Percomorphs, one of the
      copies, AR-B, has accumulated substitutions in both the ligand binding domain
      (LBD) and the DNA binding domain (DBD). CONCLUSION: The comparison of the
      mutations present in these divergent AR-B with those known in human to be
      implicated in complete, partial or mild androgen insensitivity syndrome suggests
      that the existence of two distinct AR duplicates may be correlated to specific
      functional differences that may be connected to the well-known plasticity of sex
      determination in fish. This suggests that three specific events have shaped the
      present diversity of ARs in Actinopterygians: (i) early WGD, (ii) parallel loss
      of one duplicate in several lineages and (iii) putative neofunctionalization of
      the same duplicate in percomorphs, which occurred a long time after the WGD.

PMID- 19094204
TI  - Tobacco use increases susceptibility to bacterial infection.
AB  - Active smokers and those exposed to secondhand smoke are at increased risk of
      bacterial infection. Tobacco smoke exposure increases susceptibility to
      respiratory tract infections, including tuberculosis, pneumonia and Legionnaires
      disease; bacterial vaginosis and sexually transmitted diseases, such as chlamydia
      and gonorrhoea; Helicobacter pylori infection; periodontitis; meningitis; otitis
      media; and post-surgical and nosocomial infections. Tobacco smoke compromises the
      anti-bacterial function of leukocytes, including neutrophils, monocytes, T cells
      and B cells, providing a mechanistic explanation for increased infection risk.
      Further epidemiological, clinical and mechanistic research into this important
      area is warranted.

PMID- 19094207
TI  - A discrepancy of Chlamydia trachomatis incidence and prevalence trends in Finland
      1983-2003.
AB  - BACKGROUND: Reported rates of Chlamydia trachomatis are on the rise contradicting
      the declining rates of C. trachomatis associated reproductive sequelae in Western
      countries. Population based evaluation of the real trend of C. trachomatis
      infection is important to contemplate prevention efforts. We studied C.
      trachomatis occurrence during the past 20 years in Finland comparing incidence
      rate data based on serology and reported C. trachomatis laboratory notifications.
      METHODS: A random sample of 7999 women with two consecutive pregnancies within
      five years was selected from the population of the Finnish Maternity Cohort (FMC)
      serum bank stratified by calendar year and age. C. trachomatis IgG antibodies
      were determined by a standard peptide-ELISA. The reported incidence rates of C.
      trachomatis infections based on case notifications were obtained from the
      National Registry of Infectious Diseases (NIDR). RESULTS: C. trachomatis
      seroprevalence rates decreased significantly from 1983 to 2003 both in women
      under 23 years of age (23.3% to 9.2%) and in women between 23-28-years of age
      (22.2% to 12.6%). However, seroconversion rates increased from 31 per 10000
      person years in 1983-85 to 97 per 10000 person years in 2001-2003 (incidence rate
      ratio 3.2, 95% CI, 1.1-8.7) among the older age group. Seroconversion rate was
      highest (264) in 1983-1985 in the younger age-group, then declined and
      subsequently increased again (188) in 2001-2003. The incidence based on
      seroconversions was in agreement with the reported incidence rates in both age
      groups. CONCLUSION: C. trachomatis seroprevalence rate decreased during 1983-2003
      among fertile-aged women in Finland. During the same time period incidence rates
      based both on seroconversions and reported laboratory notifications of diagnosed
      C. trachomatis infections increased. The discrepancy between the C. trachomatis
      incidence and seroprevalence trends warrants further studies.

PMID- 19094208
TI  - Core promoters are predicted by their distinct physicochemical properties in the
      genome of Plasmodium falciparum.
AB  - Little is known about the structure and distinguishing features of core promoters
      in Plasmodium falciparum. In this work, we describe the first method to
      computationally identify core promoters in this AT-rich genome. This prediction
      algorithm uses solely DNA physicochemical properties as descriptors. Our results
      add to a growing body of evidence that a physicochemical code for eukaryotic
      genomes plays a crucial role in core promoter recognition.

PMID- 19094209
TI  - tabAnti-HER2 (erbB-2) oncogene effects of phenolic compounds directly isolated
      from commercial Extra-Virgin Olive Oil (EVOO).
AB  - BACKGROUND: The effects of the olive oil-rich Mediterranean diet on breast cancer
      risk might be underestimated when HER2 (ERBB2) oncogene-positive and HER2
      negative breast carcinomas are considered together. We here investigated the anti
      HER2 effects of phenolic fractions directly extracted from Extra Virgin Olive Oil
      (EVOO) in cultured human breast cancer cell lines. METHODS: Solid phase
      extraction followed by semi-preparative high-performance liquid chromatography
      (HPLC) was used to isolate phenolic fractions from commercial EVOO. Analytical
      capillary electrophoresis coupled to mass spectrometry was performed to check for
      the composition and to confirm the identity of the isolated fractions. EVOO
      polyphenolic fractions were tested on their tumoricidal ability against HER2
      negative and HER2-positive breast cancer in vitro models using MTT, crystal
      violet staining, and Cell Death ELISA assays. The effects of EVOO polyphenolic
      fractions on the expression and activation status of HER2 oncoprotein were
      evaluated using HER2-specific ELISAs and immunoblotting procedures, respectively.
      RESULTS: Among the fractions mainly containing the single phenols hydroxytyrosol
      and tyrosol, the polyphenol acid elenolic acid, the lignans (+)-pinoresinol and 1
      (+)-acetoxypinoresinol, and the secoiridoids deacetoxy oleuropein aglycone,
      ligstroside aglycone, and oleuropein aglycone, all the major EVOO polyphenols
      (i.e. secoiridoids and lignans) were found to induce strong tumoricidal effects
      within a micromolar range by selectively triggering high levels of apoptotic cell
      death in HER2-overexpressors. Small interfering RNA-induced depletion of HER2
      protein and lapatinib-induced blockade of HER2 tyrosine kinase activity both
      significantly prevented EVOO polyphenols-induced cytotoxicity. EVOO polyphenols
      drastically depleted HER2 protein and reduced HER2 tyrosine autophosphorylation
      in a dose- and time-dependent manner. EVOO polyphenols-induced HER2
      downregulation occurred regardless the molecular mechanism contributing to HER2
      overexpression (i.e. naturally by gene amplification and ectopically driven by a
      viral promoter). Pre-treatment with the proteasome inhibitor MG132 prevented EVOO
      polyphenols-induced HER2 depletion. CONCLUSION: The ability of EVOO-derived
      polyphenols to inhibit HER2 activity by promoting the proteasomal degradation of
      the HER2 protein itself, together with the fact that humans have safely been
      ingesting secoiridoids and lignans as long as they have been consuming olives and
      OO, support the notion that the stereochemistry of these phytochemicals might
      provide an excellent and safe platform for the design of new HER2-targeting
      agents.

PMID- 19094210
TI  - Increased expression of lipocalin-type prostaglandin D2 synthase in
      osteoarthritic cartilage.
AB  - INTRODUCTION: Prostaglandin D synthase (PGDS) is responsible for the biosynthesis
      of PGD and J series, which have been shown to exhibit anti-inflammatory and
      anticatabolic effects. Two isoforms have been identified: hematopoietic- and
      lipocalin-type PGDS (H-PGDS and L-PGDS, respectively). The aims of this study
      were to investigate the expressions of H-PGDS and L-PGDS in cartilage from
      healthy donors and from patients with osteoarthritis (OA) and to characterize
      their regulation by interleukin-1-beta (IL-1beta) in cultured OA chondrocytes.
      METHODS: The expressions of H-PGDS and L-PGDS mRNA and protein in cartilage were
      analyzed by real-time reverse transcriptase-polymerase chain reaction (RT-PCR)
      and immunohistochemistry, respectively. Chondrocytes were stimulated with IL
      1beta, and the expression of L-PGDS was evaluated by real-time RT-PCR and Western
      blotting. The roles of de novo protein synthesis and of the signalling pathways
      mitogen-activated protein kinases (MAPKs), nuclear factor-kappa-B (NF-kappaB),
      and Notch were evaluated using specific pharmacological inhibitors. RESULTS: L
      PGDS and H-PGDS mRNAs were present in both healthy and OA cartilage, with higher
      levels of L-PGDS than H-PGDS (> 20-fold). The levels of L-PGDS mRNA and protein
      were increased in OA compared with healthy cartilage. Treatment of chondrocytes
      with IL-1beta upregulated L-PGDS mRNA and protein expressions as well as PGD2
      production in a dose- and time-dependent manner. The upregulation of L-PGDS by IL
      1beta was blocked by the translational inhibitor cycloheximide, indicating that
      this effect is indirect, requiring de novo protein synthesis. Specific inhibitors
      of the MAPK p38 (SB 203580) and c-jun N-terminal kinase (JNK) (SP600125) and of
      the NF-kappaB (SN-50) and Notch (DAPT) signalling pathways suppressed IL-1beta
      induced upregulation of L-PGDS expression. In contrast, an inhibitor of the
      extracellular signal-regulated kinase (ERK/MAPK) (PD98059) demonstrated no
      significant influence. We also found that PGD2 prevented IL-1beta-induced
      upregulation of L-PGDS expression. CONCLUSIONS: This is the first report
      demonstrating increased levels of L-PGDS in OA cartilage. IL-1beta may be
      responsible for this upregulation through activation of the JNK and p38 MAPK and
      NF-kappaB signalling pathways. These data suggest that L-PGDS might have an
      important role in the pathophysiology of OA.

PMID- 19094211
TI  - The immediate effects of local and adjacent acupuncture on the tibialis anterior
      muscle: a human study.
AB  - BACKGROUND: This study compares the immediate effects of local and adjacent
      acupuncture on the tibialis anterior muscle and the amount of force generated or
      strength in Kilogram Force (KGF) evaluated by a surface electromyography.
      METHODS: The study consisted of a single blinded trial of 30 subjects assigned to
      two groups: local acupoint (ST36) and adjacent acupoint (SP9). Bipolar surface
      electrodes were placed on the tibialis anterior muscle, while a force transducer
      was attached to the foot of the subject and to the floor. An electromyograph
      (EMG) connected to a computer registered the KGF and root mean square (RMS)
      before and after acupuncture at maximum isometric contraction. The RMS values and
      surface electrodes were analyzed with Student's t-test. RESULTS: Thirty subjects
      were selected from a total of 56 volunteers according to specific inclusion and
      exclusion criteria and were assigned to one of the two groups for acupuncture. A
      significant decrease in the RMS values was observed in both ST36 (t = -3.80, P =
      0,001) and SP9 (t = 6.24, P = 0.001) groups after acupuncture. There was a
      decrease in force in the ST36 group after acupuncture (t = -2.98, P = 0.006). The
      RMS values did not have a significant difference (t = 0.36, P = 0.71); however,
      there was a significant decrease in strength after acupuncture in the ST36 group
      compared to the SP9 group (t = 2.51, P = 0.01). No adverse events were found.
      CONCLUSION: Acupuncture at the local acupoint ST36 or adjacent acupoints SP9
      reduced the tibialis anterior electromyography muscle activity. However,
      acupuncture at SP9 did not decrease muscle strength while acupuncture at ST36
      did.

PMID- 19094212
TI  - Effectiveness of a grant program's efforts to promote synergy within its funded
      initiatives: perceptions of participants of the Southern Rural Access Program.
AB  - BACKGROUND: Foundations and public agencies commonly fund focused initiatives for
      individual grantees. These discrete, stand-alone initiatives can risk failure by
      being carried out in isolation. Fostering synergy among grantees' initiatives is
      one strategy proposed for promoting the success and impact of grant programs. We
      evaluate an explicit strategy to build synergy within the Robert Wood Johnson
      Foundation's Southern Rural Access Program (SRAP), which awarded grants to
      collaboratives within eight southeastern U.S. states to strengthen basic health
      care services in targeted rural counties. METHODS: We interviewed 39 key
      participants of the SRAP, including the program director within each state and
      the principal subcontractors heading the program's funded initiatives that
      supported heath professionals' recruitment, retention and training, made loans to
      health care providers, and built networks among providers. Interews were recorded
      and transcribed. Two investigators independently coded the transcripts and a
      third investigator distilled the main points. RESULTS: Participants generally
      perceived that the SRAP yielded more synergies than other grant programs in which
      they had participated and that these synergies added to the program's impact. The
      synergies most often noted were achieved through relationship building among
      grantees and with outside agencies, sharing information and know-how, sharing
      resources, combining efforts to yield greater capacity, joining voices to
      advocate for common goals, and spotting gaps in services offered and then filling
      these gaps. The SRAP's strategies that participants felt fostered synergy
      included targeting funding to culturally and geographically similar states,
      supporting complementary types of initiatives, promoting opportunities to network
      through semi-annual meetings and regular conference calls, and the advocacy
      efforts of the program's leadership. Participants noted that synergies were
      sometimes hindered by turf issues and politics and the conflicting perspectives
      and cultures of participating organizations and racial groups. Inadequate funding
      through the SRAP, restricting program involvement to only a few needy counties,
      and instances of over- and under-involvement by the program's leadership were
      sometimes felt to inhibit synergies and/or their sustainability. CONCLUSION:
      Participants of the SRAP generally perceived that the SRAP's deliberate
      strategies yielded synergies that added to the program's impact.

PMID- 19094213
TI  - Development and evaluation of a computer-based medical work assessment programme.
AB  - BACKGROUND: There are several ways to conduct a job task analysis in medical work
      environments including pencil-paper observations, interviews and questionnaires.
      However these methods implicate bias problems such as high inter-individual
      deviations and risks of misjudgement. Computer-based observation helps to reduce
      these problems. The aim of this paper is to give an overview of the development
      process of a computer-based job task analysis instrument for real-time
      observations to quantify the job tasks performed by physicians working in
      different medical settings. In addition reliability and validity data of this
      instrument will be demonstrated. METHODS: This instrument was developed in
      consequential steps. First, lists comprising tasks performed by physicians in
      different care settings were classified. Afterwards content validity of task
      lists was proved. After establishing the final task categories, computer software
      was programmed and implemented in a mobile personal computer. At least inter
      observer reliability was evaluated. Two trained observers recorded simultaneously
      tasks of the same physician. RESULTS: Content validity of the task lists was
      confirmed by observations and experienced specialists of each medical area.
      Development process of the job task analysis instrument was completed
      successfully. Simultaneous records showed adequate interrater reliability.
      CONCLUSION: Initial results of this analysis supported the validity and
      reliability of this developed method for assessing physicians' working routines
      as well as organizational context factors. Based on results using this method,
      possible improvements for health professionals' work organisation can be
      identified.

PMID- 19094214
TI  - Prenatal diagnosis of achondrogenesis type I: a case report.
AB  - INTRODUCTION: Achondrogenesis is a lethal osteochondrodysplasia characterized by
      hypoplasia of the bones and is associated with various anomalies varying in
      severity. Based on clinical, radiologic, and histopathologic features, two types
      are distinguished. CASE PRESENTATION: The prenatal ultrasound examination of a 32
      year-old Turkish woman who was referred to our clinic at 33 weeks and 6 days of
      gestation revealed fetal micromelia together with several other anomalies. The
      female baby died shortly after birth and was diagnosed with achondrogenesis type
      I based on the clinical and radiographic findings. CONCLUSION: Ultrasonography is
      important in prenatal diagnosis and for distinguishing lethal skeletal dysplasias
      in order to counsel the parents about future recurrent risks. As it is a
      uniformly lethal disease, a definitive prenatal diagnosis of achondrogenesis may
      be an indication for pregnancy termination.

PMID- 19094215
TI  - Central nervous system Toll-like receptor expression in response to Theiler's
      murine encephalomyelitis virus-induced demyelination disease in resistant and
      susceptible mouse strains.
AB  - BACKGROUND: In immunopathological diseases, such as multiple sclerosis (MS),
      genetic and environmental factors that contribute to the initiation and
      progression of the disease are often discussed. The Theiler murine
      encephalomyelitis virus-induced demyelination disease (TMEV-IDD) model used to
      study MS reflects this: genetically susceptible mice infected intra-cerebrally
      with TMEV develop a chronic demyelination disease. TMEV-IDD can be induced in
      resistant mouse strains by inducing innate immunity with lipopolysaccharide
      (LPS). Interestingly, Toll-like receptor 4 (TLR4) is the cognate receptor for LPS
      and its activation can induces up-regulation of other TLRs, such as TLR7 (the
      receptor for TMEV) and 9, known to be involved in autoimmunity. Up-regulation of
      TLRs could be involved in precipitating an autoimmune susceptible state.
      Consequently, we looked at TLR expression in the susceptible (SJL/J) and
      resistant (C57BL/6) strains of mice infected with TMEV. The resistant mice were
      induced to develop TMEV-IDD by two LPS injections following TMEV infection.
      RESULTS: Both strains were found to up-regulate multiple TLRs (TLR2, 7 and 9)
      following the TMEV infection. Expression of these TLRs and of viral mRNA was
      significantly greater in infected SJL/J mice. The susceptible SJL/J mice showed
      up-regulation of TLR3, 6 and 8, which was not seen in C57BL/6 mice. CONCLUSION:
      Expression of TLRs by susceptible mice and the up-regulation of the TLRs in
      resistant mice could participate in priming the mice toward an autoimmune state
      and develop TMEV-IDD. This could have implications on therapies that target TLRs
      to prevent the emergence of conditions such as MS in patients at risk for the
      disease.

PMID- 19094216
TI  - What determines subjective health status in patients with chronic obstructive
      pulmonary disease: importance of symptoms in subjective health status of COPD
      patients.
AB  - BACKGROUND: Subjective health status is the result of an interaction between
      physiological and psychosocial factors in patients with chronic obstructive
      pulmonary disease (COPD). However, there is little understanding of multivariate
      explanations of subjective health status in COPD. The purpose of this study was
      to explore what determines subjective health status in COPD by evaluating the
      relationships between background variables such as age and sex, predicted FEV1%,
      oxygen saturation, breathlessness, anxiety and depression, exercise capacity, and
      physical and mental health. METHODS: This study had a cross-sectional design, and
      included 100 COPD patients (51% men, mean age 66.1 years). Lung function was
      assessed by predicted FEV1%, oxygen saturation by transcutaneous pulse oximeter,
      symptoms with the St George Respiratory Questionnaire and the Hospital Anxiety
      and Depression Scale, physical function with the Incremental Shuttle Walking
      Test, and subjective health status with the SF-36 health survey. Linear
      regression analysis was used. RESULTS: Older patients reported less
      breathlessness and women reported more anxiety (p < 0.050). Women, older
      patients, those with lower predicted FEV1%, and those with greater depression had
      lower physical function (p < 0.050). Patients with higher predicted FEV1%, those
      with more breathlessness, and those with more anxiety or depression reported
      lower subjective health status (p < 0.050). Symptoms explained the greatest
      variance in subjective health status (35%-51%). CONCLUSION: Symptoms are more
      important for the subjective health status of patients with COPD than
      demographics, physiological variables, or physical function. These findings
      should be considered in the treatment and care of these patients.

PMID- 19094218
TI  - Habitat analysis of North American sand flies near veterans returning from
      leishmania-endemic war zones.
AB  - BACKGROUND: Nearly 1300 cases of leishmaniasis have been identified in American
      military personnel deployed to Iraq and Afghanistan. The symptoms of this disease
      can range from a mild, self-limiting cutaneous infection to a deadly visceral
      infection and are not prevented by chemoprophylaxis or immunization. Effective
      treatments, however, are available. The disease-causing parasite is spread
      through the bite of the female sand fly. Although the disease occurs in both the
      Old World and the New World, the parasite species differ between the hemispheres.
      The large number of cases in military veterans has caused some concern that Old
      World, temperate-adapted parasite species could be introduced into the native
      sand fly populations of American military facilities where veterans of the
      current conflicts return following their deployments. This paper reports part of
      a larger study to analyze the risk of such an accidental importation. Four
      potential habitats on two large Army facilities in the Southeast United States
      were surveyed to determine relative sand fly density. The National Land Cover Map
      was used to provide sand fly density prediction maps by habitat. RESULTS: Sand
      fly density was significantly higher in deciduous forest and even higher at the
      interface between forest and open grassland. The evergreen forest and
      agricultural fields supported very low densities. On Fort Campbell, KY, the
      percentage of land covered by suitable habitat was very high. A sand fly density
      prediction map identified large tracts of land where infected individuals would
      be at higher risk of exposure to sand fly bites, resulting in an increased risk
      of introducing the parasite to a native insect population. On Fort Bragg, NC,
      however, commercial farming of long leaf pine reduced the percentage of the land
      covered in vegetation suitable for the support of sand flies. The risk of
      introducing an exotic Leishmania spp. on Fort Bragg, therefore, is considered to
      be much lower than on Fort Campbell. CONCLUSION: A readily available land cover
      product can be used at the regional level to identify areas of sand fly habitat
      where human populations may be at higher risk of exposure. The sand fly density
      prediction maps can be used to direct further surveillance, insect control, or
      additional patient monitoring of potentially infected soldiers.

PMID- 19094217
TI  - Topical application of entry inhibitors as "virustats" to prevent sexual
      transmission of HIV infection.
AB  - With the continuing march of the AIDS epidemic and little hope for an effective
      vaccine in the near future, work to develop a topical strategy to prevent HIV
      infection is increasingly important. This stated, the track record of large scale
      "microbicide" trials has been disappointing with nonspecific inhibitors either
      failing to protect women from infection or even increasing HIV acquisition. Newer
      strategies that target directly the elements needed for viral entry into cells
      have shown promise in non-human primate models of HIV transmission and as these
      agents have not yet been broadly introduced in regions of highest HIV prevalence,
      they are particularly attractive for prophylaxis. We review here the agents that
      can block HIV cellular entry and that show promise as topical strategies or
      "virustats" to prevent mucosal transmission of HIV infection.

PMID- 19094219
TI  - An initial application of computerized adaptive testing (CAT) for measuring
      disability in patients with low back pain.
AB  - BACKGROUND: Recent approaches to outcome measurement involving Computerized
      Adaptive Testing (CAT) offer an approach for measuring disability in low back
      pain (LBP) in a way that can reduce the burden upon patient and professional. The
      aim of this study was to explore the potential of CAT in LBP for measuring
      disability as defined in the International Classification of Functioning,
      Disability and Health (ICF) which includes impairments, activity limitation, and
      participation restriction. METHODS: 266 patients with low back pain answered
      questions from a range of widely used questionnaires. An exploratory factor
      analysis (EFA) was used to identify disability dimensions which were then
      subjected to Rasch analysis. Reliability was tested by internal consistency and
      person separation index (PSI). Discriminant validity of disability levels were
      evaluated by Spearman correlation coefficient (r), intraclass correlation
      coefficient [ICC(2,1)] and the Bland-Altman approach. A CAT was developed for
      each dimension, and the results checked against simulated and real applications
      from a further 133 patients. RESULTS: Factor analytic techniques identified two
      dimensions named "body functions" and "activity-participation". After deletion of
      some items for failure to fit the Rasch model, the remaining items were mostly
      free of Differential Item Functioning (DIF) for age and gender. Reliability
      exceeded 0.90 for both dimensions. The disability levels generated using all
      items and those obtained from the real CAT application were highly correlated
      (i.e. > 0.97 for both dimensions). On average, 19 and 14 items were needed to
      estimate the precise disability levels using the initial CAT for the first and
      second dimension. However, a marginal increase in the standard error of the
      estimate across successive iterations substantially reduced the number of items
      required to make an estimate. CONCLUSION: Using a combination approach of EFA and
      Rasch analysis this study has shown that it is possible to calibrate items onto a
      single metric in a way that can be used to provide the basis of a CAT
      application. Thus there is an opportunity to obtain a wide variety of information
      to evaluate the biopsychosocial model in its more complex forms, without
      necessarily increasing the burden of information collection for patients.

PMID- 19094220
TI  - G-spots cause incorrect expression measurement in Affymetrix microarrays.
AB  - BACKGROUND: High Density Oligonucleotide arrays (HDONAs), such as the Affymetrix
      HG-U133A GeneChip, use sets of probes chosen to match specified genes, with the
      expectation that if a particular gene is highly expressed then all the probes in
      that gene's probe set will provide a consistent message signifying the gene's
      presence. However, probes that contain a G-spot (a sequence of four or more
      guanines) behave abnormally and it has been suggested that these probes are
      responding to some biochemical effect such as the formation of G-quadruplexes.
      RESULTS: We have tested this expectation by examining the correlation
      coefficients between pairs of probes using the data on thousands of arrays that
      are available in the NCBI Gene Expression Omnibus (GEO) repository. We confirm
      the finding that G-spot probes are poorly correlated with others in their
      probesets and reveal that, by contrast, they are highly correlated with one
      another. We demonstrate that the correlation is most marked when the G-spot is at
      the 5' end of the probe. CONCLUSION: Since these G-spot probes generally show
      little correlation with the other members of their probesets they are not fit for
      purpose and their values should be excluded when calculating gene expression
      values. This has serious implications, since more than 40% of the probesets in
      the HG-U133A GeneChip contain at least one such probe. Future array designs
      should avoid these untrustworthy probes.

PMID- 19094221
TI  - Spatio-temporal analysis of the relationship between WNV dissemination and
      environmental variables in Indianapolis, USA.
AB  - BACKGROUND: This study developed a multi-temporal analysis on the relationship
      between West Nile Virus (WNV) dissemination and environmental variables by using
      an integrated approach of remote sensing, GIS, and statistical techniques. WNV
      mosquito cases in seven months (April-October) of the six years (2002-2007) were
      collected in Indianapolis, USA. Epidemic curves were plotted to identify the
      temporal outbreaks of WNV. Spatial-temporal analysis and k-mean cluster analysis
      were further applied to determine the high-risk areas. Finally, the relationship
      between environmental variables and WNV outbreaks were examined by using
      Discriminant Analysis. RESULTS: The results show that the WNV epidemic curve
      reached its peak in August for all years in the study area except in 2007, where
      the peak was reached in July. WNV dissemination started from the central
      longitudinal corridor of the city and spread out to the east and west. Different
      years and seasons had different high-risk areas, but the southwest and southeast
      corners show the highest risk for WNV infection due to their high percentages of
      agriculture and water sources. CONCLUSION: Major environmental factors
      contributing to the outbreak of WNV in Indianapolis were the percentages of
      agriculture and water, total length of streams, and total size of wetlands. This
      study provides important information for urban public health prevention and
      management. It also contributes to the optimization of mosquito control and
      arrangement of future sampling efforts.

PMID- 19094222
TI  - Seizure control in patients with epilepsy: the physician vs. medication factors.
AB  - BACKGROUND: Little is known about the relationship between types of healthcare
      providers and outcomes in patients with epilepsy. This study compares the
      relative effects of provider type (epileptologist vs. other neurologist) and
      pharmacologic treatment (newer vs. older antiepileptic drugs) on seizure control
      in patients with epilepsy. METHODS: We conducted a retrospective study of
      patients with medication-resistant epilepsy. Consecutive charts of 200 patients
      were abstracted using a standard case report form. For each patient, data
      included seizure frequency and medication use prior to, and while being treated
      by an epileptologist. Changes in seizure frequency were modeled using a
      generalized linear model. RESULTS: After transferring care from a general
      neurologist to specialized epilepsy center, patients experienced fewer seizures
      (p < 0.001) and were more frequently seizure-free (p < 0.001). The improved
      seizure control was not related to treatment with newer vs. older antiepileptic
      drugs (p = 0.305). CONCLUSION: Our findings suggest an association between
      subspecialty epilepsy care and improved seizure control in patients with
      medication-resistant epilepsy. Further research should prospectively determine
      whether patients with medication-resistant epilepsy would benefit from being
      routinely referred to an epilepsy specialist.

PMID- 19094223
TI  - KEGG spider: interpretation of genomics data in the context of the global gene
      metabolic network.
AB  - KEGG spider is a web-based tool for interpretation of experimentally derived gene
      lists in order to gain understanding of metabolism variations at a genomic level.
      KEGG spider implements a 'pathway-free' framework that overcomes a major
      bottleneck of enrichment analyses: it provides global models uniting genes from
      different metabolic pathways. Analyzing a number of experimentally derived gene
      lists, we demonstrate that KEGG spider provides deeper insights into metabolism
      variations in comparison to existing methods.

PMID- 19094224
TI  - Automated paleontology of repetitive DNA with REANNOTATE.
AB  - BACKGROUND: Dispersed repeats are a major component of eukaryotic genomes and
      drivers of genome evolution. Annotation of DNA sequences homologous to known
      repetitive elements has been mainly performed with the program REPEATMASKER.
      Sequences annotated by REPEATMASKER often correspond to fragments of repetitive
      elements resulting from the insertion of younger elements or other
      rearrangements. Although REPEATMASKER annotation is indispensable for studying
      genome biology, this annotation does not contain much information on the common
      origin of fossil fragments that share an insertion event, especially where
      clusters of nested insertions of repetitive elements have occurred. RESULTS: Here
      I present REANNOTATE, a computational tool to process REPEATMASKER annotation for
      automated i) defragmentation of dispersed repetitive elements, ii) resolution of
      the temporal order of insertions in clusters of nested elements, and iii)
      estimating the age of the elements, if they have long terminal repeats. I have re
      annotated the repetitive content of human chromosomes, providing evidence for a
      recent expansion of satellite repeats on the Y chromosome and, from the
      retroviral age distribution, for a higher rate of evolution on the Y relative to
      autosomes. CONCLUSION: REANNOTATE is ready to process existing annotation for
      automated evolutionary analysis of all types of complex repeats in any genome.
      The tool is freely available under the GPL at
      http://www.bioinformatics.org/reannotate.

PMID- 19094225
TI  - Prospective controlled randomized trial on prevention of postoperative abdominal
      adhesions by Icodextrin 4% solution after laparotomic operation for small bowel
      obstruction caused by adherences [POPA study: Prevention of Postoperative
      Adhesions on behalf of the World Society of Emergency Surgery].
AB  - BACKGROUND: Adhesive small intestine occlusion [ASIO] is an important cause of
      hospital admission placing a substantial burden on healthcare systems worldwide.
      Often times, ASIO is associated with significant morbidity and
      mortality.Icodextrin 4% solution [Adept, Shire Pharmaceuticals, UK] is a high
      molecular-weight a-1,4 glucose polymer that is approved in Europe for use as an
      intra-operative lavage and a post-operative instillate to reduce the occurrence
      of post-surgery intra-abdominal adhesions.There are no randomized trials on the
      use of this solution to prevent adhesions after ASIO operation in current medical
      literature.The current clinical study evaluates the safety and effectiveness of
      Icodextrin 4% for decreasing the incidence, extent, and severity of adhesions in
      patients after abdominal surgery for ASIO. DESIGN: The study project is a
      prospective, randomized controlled investigation performed in the Department of
      Transplant, General and Emergency Surgery of St. Orsola-Malpighi University
      Hospital [Bologna, Italy]. The study is designed and conducted in compliance with
      the principles of Good Clinical Practice regulations.The study compares the
      results of Icodextrin 4% against a control group who does not receive anti
      adhesion treatment. This randomized study uses a double-blind procedure to
      evaluate efficacy end points. In other words, designated third party individuals
      who are unaware of the treatment assigned to the patients to assess adhesion
      formation. TRIAL REGISTRATION NUMBER: ISRCTN22061989 Prospective controlled
      randomized trial on Prevention of Postoperative Abdominal Adhesions by Icodextrin
      4% solution after laparotomic operation for small bowel obstruction caused by
      adherences[POPA study: Prevention of Postoperative Adhesions].

PMID- 19094226
TI  - Effective transvascular delivery of nanoparticles across the blood-brain tumor
      barrier into malignant glioma cells.
AB  - BACKGROUND: Effective transvascular delivery of nanoparticle-based
      chemotherapeutics across the blood-brain tumor barrier of malignant gliomas
      remains a challenge. This is due to our limited understanding of nanoparticle
      properties in relation to the physiologic size of pores within the blood-brain
      tumor barrier. Polyamidoamine dendrimers are particularly small multigenerational
      nanoparticles with uniform sizes within each generation. Dendrimer sizes increase
      by only 1 to 2 nm with each successive generation. Using functionalized
      polyamidoamine dendrimer generations 1 through 8, we investigated how
      nanoparticle size influences particle accumulation within malignant glioma cells.
      METHODS: Magnetic resonance and fluorescence imaging probes were conjugated to
      the dendrimer terminal amines. Functionalized dendrimers were administered
      intravenously to rodents with orthotopically grown malignant gliomas.
      Transvascular transport and accumulation of the nanoparticles in brain tumor
      tissue was measured in vivo with dynamic contrast-enhanced magnetic resonance
      imaging. Localization of the nanoparticles within glioma cells was confirmed ex
      vivo with fluorescence imaging. RESULTS: We found that the intravenously
      administered functionalized dendrimers less than approximately 11.7 to 11.9 nm in
      diameter were able to traverse pores of the blood-brain tumor barrier of RG-2
      malignant gliomas, while larger ones could not. Of the permeable functionalized
      dendrimer generations, those that possessed long blood half-lives could
      accumulate within glioma cells. CONCLUSION: The therapeutically relevant upper
      limit of blood-brain tumor barrier pore size is approximately 11.7 to 11.9 nm.
      Therefore, effective transvascular drug delivery into malignant glioma cells can
      be accomplished by using nanoparticles that are smaller than 11.7 to 11.9 nm in
      diameter and possess long blood half-lives.

PMID- 19094227
TI  - The epidemiology of intensive care unit-acquired hyponatraemia and hypernatraemia
      in medical-surgical intensive care units.
AB  - INTRODUCTION: Although sodium disturbances are common in hospitalised patients,
      few studies have specifically investigated the epidemiology of sodium
      disturbances in the intensive care unit (ICU). The objectives of this study were
      to describe the incidence of ICU-acquired hyponatraemia and hypernatraemia and
      assess their effects on outcome in the ICU. METHODS: We identified 8142
      consecutive adults (18 years of age or older) admitted to three medical-surgical
      ICUs between 1 January 2000 and 31 December 2006 who were documented to have
      normal serum sodium levels (133 to 145 mmol/L) during the first day of ICU
      admission. ICU acquired hyponatraemia and hypernatraemia were respectively
      defined as a change in serum sodium concentration to below 133 mmol/L or above
      145 mmol/L following day one in the ICU. RESULTS: A first episode of ICU-acquired
      hyponatraemia developed in 917 (11%) patients and hypernatraemia in 2157 (26%)
      patients with an incidence density of 3.1 and 7.4 per 100 days of ICU admission,
      respectively, during 29,142 ICU admission days. The incidence of both ICU
      acquired hyponatraemia (age, admission diagnosis, Acute Physiology and Chronic
      Health Evaluation (APACHE) II score, length of ICU stay, level of consciousness,
      serum glucose level, body temperature, serum potassium level) and ICU-acquired
      hypernatraemia (baseline creatinine, APACHE II score, mechanical ventilation,
      length of ICU stay, body temperature, serum potassium level, level of care)
      varied according to patients' characteristics. Compared with patients with normal
      serum sodium levels, hospital mortality was increased in patients with ICU
      acquired hyponatraemia (16% versus 28%, p < 0.001) and ICU-acquired
      hypernatraemia (16% versus 34%, p < 0.001). CONCLUSIONS: ICU-acquired
      hyponatraemia and hypernatraemia are common in critically ill patients and are
      associated with increased risk of hospital mortality.

PMID- 19094228
TI  - The influence of genetic variation in 30 selected genes on the clinical
      characteristics of early onset breast cancer.
AB  - INTRODUCTION: Common variants that alter breast cancer risk are being discovered.
      Here, we determine how these variants influence breast cancer prognosis, risk and
      tumour characteristics. METHODS: We selected 1,001 women with early onset
      nonfamilial invasive breast cancer from the Prospective study of Outcomes in
      Sporadic versus Hereditary breast cancer (POSH) cohort and genotyped 206 single
      nucleotide polymorphisms (SNPs) across 30 candidate genes. After quality control,
      899 cases and 133 SNPs remained. Survival analyses were used to identify SNPs
      associated with prognosis and determine their interdependency with recognized
      prognostic factors. To identify SNPs that alter breast cancer risk, association
      tests were used to compare cases with controls from the Wellcome Trust Case
      Control Consortium. To search for SNPs affecting tumour biology, cases were
      stratified into subgroups according to oestrogen receptor (ER) status and grade
      and tested for association. RESULTS: We confirmed previous associations between
      increased breast cancer risk and SNPs in CASP8, TOX3 (previously known as TNRC9)
      and ESR1. Analysis of prognosis identified eight SNPs in six genes (MAP3K1,
      DAPK1, LSP1, MMP7, TOX3 and ESR1) and one region without genes on 8q24 that are
      associated with survival. For MMP7, TOX3 and MAP3K1 the effects on survival are
      independent of the main recognized clinical prognostic factors. The SNP in 8q24
      is more weakly associated with independent effects on survival. Once grade and
      pathological nodal status (pN stage) were taken into account, SNPs in ESR1 and
      LSP1 showed no independent survival difference, whereas the effects of the DAPK1
      SNP were removed when correcting for ER status. Interestingly, effects on
      survival for SNPs in ESR1 were most significant when only ER-positive tumours
      were examined. Stratifying POSH cases by tumour characteristics identified SNPs
      in FGFR2 and TOX3 associated with ER-positive disease and SNPs in ATM associated
      with ER-negative disease. CONCLUSIONS: We have demonstrated that several SNPs are
      associated with survival. In some cases this appears to be due to an effect on
      tumour characteristics known to have a bearing on prognosis; in other cases the
      effect appears to be independent of these prognostic factors. These findings
      require validation by further studies in similar patient groups.

PMID- 19094229
TI  - A simple and rapid Hepatitis A Virus (HAV) titration assay based on antibiotic
      resistance of infected cells: evaluation of the HAV neutralization potency of
      human immune globulin preparations.
AB  - BACKGROUND: Hepatitis A virus (HAV), the causative agent of acute hepatitis in
      humans, is an atypical Picornaviridae that grows poorly in cell culture. HAV
      titrations are laborious and time-consuming because the virus in general does not
      cause cytopathic effect and is detected by immunochemical or molecular probes.
      Simple HAV titration assays could be developed using currently available viral
      construct containing selectable markers. RESULTS: We developed an antibiotic
      resistance titration assay (ARTA) based on the infection of human hepatoma cells
      with a wild type HAV construct containing a blasticidin (Bsd) resistance gene.
      Human hepatoma cells infected with the HAV-Bsd construct survived selection with
      2 microg/ml of blasticidin whereas uninfected cells died within a few days. At 8
      days postinfection, the color of the pH indicator phenol red in cell culture
      media correlated with the presence of HAV-Bsd-infected blasticidin-resistant
      cells: an orange-to-yellow color indicated the presence of growing cells whereas
      a pink-to-purple color indicated that the cells were dead. HAV-Bsd titers were
      determined by an endpoint dilution assay based on the color of the cell culture
      medium scoring orange-to-yellow wells as positive and pink-to-purple wells as
      negative for HAV. As a proof-of-concept, we used the ARTA to evaluate the HAV
      neutralization potency of two commercially available human immune globulin (IG)
      preparations and a WHO International Standard for anti-HAV. The three IG
      preparations contained comparable levels of anti-HAV antibodies that neutralized
      approximately 1.5 log of HAV-Bsd. Similar neutralization results were obtained in
      the absence of blasticidin by an endpoint dilution ELISA at 2 weeks
      postinfection. CONCLUSION: The ARTA is a simple and rapid method to determine HAV
      titers without using HAV-specific probes. We determined the HAV neutralization
      potency of human IG preparations in 8 days by ARTA compared to the 14 days
      required by the endpoint dilution ELISA. The ARTA reduced the labour, time, and
      cost of HAV titrations making it suitable for high throughput screening of sera
      and antivirals, determination of anti-HAV antibodies in human immune globulin
      preparations, and research applications that involve the routine evaluation of
      HAV titers.

PMID- 19094230
TI  - Biological processes, properties and molecular wiring diagrams of candidate low
      penetrance breast cancer susceptibility genes.
AB  - BACKGROUND: Recent advances in whole-genome association studies (WGASs) for human
      cancer risk are beginning to provide the part lists of low-penetrance
      susceptibility genes. However, statistical analysis in these studies is
      complicated by the vast number of genetic variants examined and the weak effects
      observed, as a result of which constraints must be incorporated into the study
      design and analytical approach. In this scenario, biological attributes beyond
      the adjusted statistics generally receive little attention and, more importantly,
      the fundamental biological characteristics of low-penetrance susceptibility genes
      have yet to be determined. METHODS: We applied an integrative approach for
      identifying candidate low-penetrance breast cancer susceptibility genes, their
      characteristics and molecular networks through the analysis of diverse sources of
      biological evidence. RESULTS: First, examination of the distribution of Gene
      Ontology terms in ordered WGAS results identified asymmetrical distribution of
      Cell Communication and Cell Death processes linked to risk. Second, analysis of
      11 different types of molecular or functional relationships in genomic and
      proteomic data sets defined the "omic" properties of candidate genes: i/
      differential expression in tumors relative to normal tissue; ii/ somatic genomic
      copy number changes correlating with gene expression levels; iii/ differentially
      expressed across age at diagnosis; and iv/ expression changes after BRCA1
      perturbation. Finally, network modeling of the effects of variants on germline
      gene expression showed higher connectivity than expected by chance between novel
      candidates and with known susceptibility genes, which supports functional
      relationships and provides mechanistic hypotheses of risk. CONCLUSION: This study
      proposes that cell communication and cell death are major biological processes
      perturbed in risk of breast cancer conferred by low-penetrance variants, and
      defines the common omic properties, molecular interactions and possible
      functional effects of candidate genes and proteins.

PMID- 19094231
TI  - Hemolysis and hyperhomocysteinemia caused by cobalamin deficiency: three case
      reports and review of the literature.
AB  - Concurrent hemolysis in patients with vitamin B12 deficiency is a well-recognized
      phenomenon and has been attributed to intramedullary destruction of erythrocytes
      (ineffective erythropoiesis). Recent studies revealed that homocysteine increased
      the risk of hemolysis in vitamin B12 deficiency in vitro and there is a high
      frequency (30%) of vitamin B12 deficiency in asymptomatic patients with
      homozygous methylene tetrahydrofolate reductase (MTHFR) C677T mutation, a known
      cause of hyperhomocysteinemia. Here we report three patients with MTHFR mutations
      and vitamin B12 deficiency presenting with hemolytic anemia and severely elevated
      homocysteine levels. Patients demonstrated complete resolution of hemolysis with
      simultaneous normalization of serum homocysteine levels after vitamin B12
      treatments. We reviewed pertinent literature, and hypothesized that hemolytic
      anemia may be more prevalent in patients who have a coexisting MTHFR gene
      mutation and vitamin B12 deficiency possibly related to severely elevated
      homocysteine levels. The hemolysis in these cases occurred predominantly in
      peripheral blood likely due to the combined effects of structurally defective
      erythrocytes and homocysteine-induced endothelial damage with microangiopathy.

PMID- 19094232
TI  - Three decades (1978-2008) of Advanced Trauma Life Support (ATLS) practice revised
      and evidence revisited.
AB  - The Advanced Trauma Life Support (ATLS) Program was developed to teach doctors
      one safe, reliable method to assess and initially manage the trauma patient. The
      ATLS principles represents an organized approach for evaluation and management of
      seriously injured patients and offers a foundation of common knowledge for all
      members of the trauma team. After 3 decades of teaching (1978-2008) of ATLS
      worldwide one should intuitively perceive that the evidence for the effect of
      ATLS teaching on the improved management of the injured patient be well
      established. This editorial addresses aspects of trauma education with needs for
      further development of better evidence of best practice.

PMID- 19094233
TI  - Filter survival time and requirement of blood products in patients with severe
      sepsis receiving drotrecogin alfa (activated) and requiring renal replacement
      therapy.
AB  - INTRODUCTION: Drotrecogin alfa (activated) (DrotAA) is licensed in the United
      States and the European Union for the treatment of severe sepsis with multiple
      organ failure. Patients with severe sepsis on renal replacement therapy (RRT),
      who typically receive additional anticoagulation to prevent circuit clotting, may
      be at higher risk of bleeding when DrotAA is administered in addition to standard
      anticoagulation. However, the effects of DrotAA on filter duration in the absence
      of additional anticoagulation have not been established. The aim of this study
      was to analyse the filter survival time (FST), and to quantify the requirement of
      packed red cells (PRC) and blood products during DrotAA infusion. METHODS: This
      was a single-centre, retrospective observational study conducted in an adult
      intensive care unit (ICU). Thirty-five patients with severe sepsis who had
      received both RRT and DrotAA were identified, and all relevant clinical and
      laboratory data were retrieved from the departmental electronic patient record.
      We compared haemofilter parameters, requirement of blood products and
      haemodynamic data recorded during RRT and the infusion of DrotAA with those
      recorded on RRT with standard anticoagulation after the DrotAA infusion had been
      completed (post-DrotAA). RESULTS: The proportion of filter changes due to filter
      clotting was similar during DrotAA infusion and with conventional anticoagulation
      post-DrotAA infusion. There was no difference in the FST and filter parameters
      during DrotAA in the presence or absence of additional anticoagulation with
      heparin or epoprostenol. A similar proportion of patients required red cell
      transfusion, although a greater proportion of patients received platelet and
      fresh frozen plasma during DrotAA infusion compared with the post-DrotAA period
      with no difference between medical and surgical patients. CONCLUSIONS: Additional
      anticoagulation during DrotAA infusion does not appear to improve FST. The use of
      DrotAA in patients with severe sepsis requiring RRT is safe and is not associated
      with an increased need for PRC transfusion or major bleeding events.

PMID- 19094234
TI  - Complex fate of paralogs.
AB  - BACKGROUND: Thanks to recent high coverage mass-spectrometry studies and
      reconstructed protein complexes, we are now in an unprecedented position to study
      the evolution of biological systems. Gene duplications, known to be a major
      source of innovation in evolution, can now be readily examined in the context of
      protein complexes. RESULTS: We observe that paralogs operating in the same
      complex fulfill different roles: mRNA dosage increase for more than a hundred
      cytosolic ribosomal proteins, mutually exclusive participation of at least 54
      paralogs resulting in alternative forms of complexes, and 24 proteins
      contributing to bona fide structural growth. Inspection of paralogous proteins
      participating in two independent complexes shows that an ancient, pre-duplication
      protein functioned in both multi-protein assemblies and a gene duplication event
      allowed the respective copies to specialize and split their roles. CONCLUSION:
      Variants with conditionally assembled, paralogous subunits likely have played a
      role in yeast's adaptation to anaerobic conditions. In a number of cases the gene
      duplication has given rise to one duplicate that is no longer part of a protein
      complex and shows an accelerated rate of evolution. Such genes could provide the
      raw material for the evolution of new functions.

PMID- 19094235
TI  - GeneChaser: identifying all biological and clinical conditions in which genes of
      interest are differentially expressed.
AB  - BACKGROUND: The amount of gene expression data in the public repositories, such
      as NCBI Gene Expression Omnibus (GEO) has grown exponentially, and provides a
      gold mine for bioinformaticians, but has not been easily accessible by biologists
      and clinicians. RESULTS: We developed an automated approach to annotate and
      analyze all GEO data sets, including 1,515 GEO data sets from 231 microarray
      types across 42 species, and performed 12,658 group versus group comparisons of
      24 GEO-specified types. We then built GeneChaser, a web server that enables
      biologists and clinicians without bioinformatics skills to easily identify
      biological and clinical conditions in which a gene or set of genes was
      differentially expressed. GeneChaser displays these conditions in graphs, gives
      statistical comparisons, allows sort/filter functions and provides access to the
      original studies.We performed a single gene search for Nanog and a multiple gene
      search for Nanog, Oct4, Sox2 and LIN28, confirmed their roles in embryonic stem
      cell development, identified several drugs that regulate their expression, and
      suggested their potential roles in sex determination, abnormal sperm morphology,
      malaria infection, and cancer. CONCLUSION: We demonstrated that GeneChaser is a
      powerful tool to elucidate information on function, transcriptional regulation,
      drug-response and clinical implications for genes of interest.

PMID- 19094236
TI  - Genome wide association for substance dependence: convergent results from
      epidemiologic and research volunteer samples.
AB  - BACKGROUND: Dependences on addictive substances are substantially-heritable
      complex disorders whose molecular genetic bases have been partially elucidated by
      studies that have largely focused on research volunteers, including those
      recruited in Baltimore. Maryland. Subjects recruited from the Baltimore site of
      the Epidemiological Catchment Area (ECA) study provide a potentially-useful
      comparison group for possible confounding features that might arise from
      selecting research volunteer samples of substance dependent and control
      individuals. We now report novel SNP (single nucleotide polymorphism) genome wide
      association (GWA) results for vulnerability to substance dependence in ECA
      participants, who were initially ascertained as members of a probability sample
      from Baltimore, and compare the results to those from ethnically-matched
      Baltimore research volunteers. RESULTS: We identify substantial overlap between
      the home address zip codes reported by members of these two samples. We find
      overlapping clusters of SNPs whose allele frequencies differ with nominal
      significance between substance dependent vs control individuals in both samples.
      These overlapping clusters of nominally-positive SNPs identify 172 genes in ways
      that are never found by chance in Monte Carlo simulation studies. Comparison with
      data from human expressed sequence tags suggests that these genes are expressed
      in brain, especially in hippocampus and amygdala, to extents that are greater
      than chance. CONCLUSION: The convergent results from these probability sample and
      research volunteer sample datasets support prior genome wide association results.
      They fail to support the idea that large portions of the molecular genetic
      results for vulnerability to substance dependence derive from factors that are
      limited to research volunteers.

PMID- 19094237
TI  - Alterations in cell growth and signaling in ErbB3 binding protein-1 (Ebp1)
      deficient mice.
AB  - BACKGROUND: The ErbB3 binding protein-1 (Ebp1) belongs to a family of DNA/RNA
      binding proteins implicated in cell growth, apoptosis and differentiation.
      However, the physiological role of Ebp1 in the whole organism is not known.
      Therefore, we generated Ebp1-deficient mice carrying a gene trap insertion in
      intron 2 of the Ebp1 (pa2g4) gene. RESULTS: Ebp1-/- mice were on average 30%
      smaller than wild type and heterozygous sex matched littermates. Growth
      retardation was apparent from Day 10 until Day 30. IGF-1 production and IGBP-3
      and 4 protein levels were reduced in both embryo fibroblasts and adult knock-out
      mice. The proliferation of fibroblasts derived from Day 12.5 knock out embryos
      was also decreased as compared to that of wild type cells. Microarray expression
      analysis revealed changes in genes important in cell growth including members of
      the MAPK signal transduction pathway. In addition, the expression or activation
      of proliferation related genes such as AKT and the androgen receptor, previously
      demonstrated to be affected by Ebp1 expression in vitro, was altered in adult
      tissues. CONCLUSION: These results indicate that Ebp1 can affect growth in an
      animal model, but that the expression of proliferation related genes is cell and
      context specific. The Ebp1-/- mouse line represents a new in vivo model to
      investigate Ebp1 function in the whole organism.

PMID- 19094238
TI  - Singular value decomposition-based regression identifies activation of endogenous
      signaling pathways in vivo.
AB  - The ability to detect activation of signaling pathways based solely on gene
      expression data represents an important goal in biological research. We tested
      the sensitivity of singular value decomposition-based regression by focusing on
      functional interactions between the Ras and transforming growth factor beta
      signaling pathways. Our findings demonstrate that this approach is sufficiently
      sensitive to detect the secondary activation of endogenous signaling pathways as
      it occurs through crosstalk following ectopic activation of a primary pathway.

PMID- 19094239
TI  - Genomic sequence and activity of KS10, a transposable phage of the Burkholderia
      cepacia complex.
AB  - BACKGROUND: The Burkholderia cepacia complex (BCC) is a versatile group of Gram
      negative organisms that can be found throughout the environment in sources such
      as soil, water, and plants. While BCC bacteria can be involved in beneficial
      interactions with plants, they are also considered opportunistic pathogens,
      specifically in patients with cystic fibrosis and chronic granulomatous disease.
      These organisms also exhibit resistance to many antibiotics, making conventional
      treatment often unsuccessful. KS10 was isolated as a prophage of B. cenocepacia
      K56-2, a clinically relevant strain of the BCC. Our objective was to sequence the
      genome of this phage and also determine if this prophage encoded any virulence
      determinants. RESULTS: KS10 is a 37,635 base pairs (bp) transposable phage of the
      opportunistic pathogen Burkholderia cenocepacia. Genome sequence analysis and
      annotation of this phage reveals that KS10 shows the closest sequence homology to
      Mu and BcepMu. KS10 was found to be a prophage in three different strains of B.
      cenocepacia, including strains K56-2, J2315, and C5424, and seven tested clinical
      isolates of B. cenocepacia, but no other BCC species. A survey of 23 strains and
      20 clinical isolates of the BCC revealed that KS10 is able to form plaques on
      lawns of B. ambifaria LMG 19467, B. cenocepacia PC184, and B. stabilis LMG 18870.
      CONCLUSION: KS10 is a novel phage with a genomic organization that differs from
      most phages in that its capsid genes are not aligned into one module but rather
      separated by approximately 11 kb, giving evidence of one or more prior genetic
      rearrangements. There were no potential virulence factors identified in KS10,
      though many hypothetical proteins were identified with no known function.

PMID- 19094240
TI  - Development and preliminary validation of the 'Caring for Country' questionnaire:
      measurement of an Indigenous Australian health determinant.
AB  - BACKGROUND: 'Caring for Country' is defined as Indigenous participation in
      interrelated activities with the objective of promoting ecological and human
      health. Ecological services on Indigenous-owned lands are belatedly attracting
      some institutional investment. However, the health outcomes associated with
      Indigenous participation in 'caring for country' activities have never been
      investigated. The aims of this study were to pilot and validate a questionnaire
      measuring caring for country as an Indigenous health determinant and to relate it
      to an external reference, obesity. METHODS: Purposively sampled participants were
      301 Indigenous adults aged 15 to 54 years, recruited during a cross-sectional
      program of preventive health checks in a remote Australian community.
      Questionnaire validation was undertaken with psychometric tests of internal
      consistency, reliability, exploratory factor analysis and confirmatory one-factor
      congeneric modelling. Accurate item weightings were derived from the model and
      used to create a single weighted composite score for caring for country. Multiple
      linear regression modelling was used to test associations between the caring for
      country score and body mass index adjusting for socio-demographic factors and
      health behaviours. RESULTS: The questionnaire demonstrated adequate internal
      consistency, test-retest validity and proxy-respondent validity. Exploratory
      factor analysis of the 'caring for country' items produced a single factor
      solution that was confirmed via one-factor congeneric modelling. A significant
      and substantial association between greater participation in caring for country
      activities and lower body mass index was demonstrated. Adjusting for socio
      demographic factors and health behaviours, an inter-quartile range rise in caring
      for country scores was associated with 6.1 Kg and 5.3 Kg less body weight for non
      pregnant women and men respectively. CONCLUSION: This study indicates preliminary
      support for the validity of the caring for country concept and a questionnaire
      designed to measure it. This study also highlights the importance of
      investigating Indigenous-asserted health promotion activities. Further studies in
      similar populations are merited to test the generalisability of this
      questionnaire and to explore associations with other important Indigenous health
      outcomes.

PMID- 19094241
TI  - Defence reactions in the apoplastic proteome of oilseed rape (Brassica napus var.
      napus) attenuate Verticillium longisporum growth but not disease symptoms.
AB  - BACKGROUND: Verticillium longisporum is one of the most important pathogens of
      Brassicaceae that remains strictly in the xylem during most stages of its
      development. It has been suggested that disease symptoms are associated with
      clogging of xylem vessels. The aim of our study was to investigate extracellular
      defence reactions induced by V. longisporum in the xylem sap and leaf apoplast of
      Brassica napus var. napus in relation to the development of disease symptoms,
      photosynthesis and nutrient status. RESULTS: V. longisporum (strain VL43) did not
      overcome the hypocotyl barrier until 3 weeks after infection although the plants
      showed massive stunting of the stem and mild leaf chlorosis. During this initial
      infection phase photosynthetic carbon assimilation, transpiration rate and
      nutrient elements in leaves were not affected in VL43-infected compared to non
      infected plants. Proteome analysis of the leaf apoplast revealed 170 spots after
      2-D-protein separation, of which 12 were significantly enhanced in response to
      VL43-infection. LS-MS/MS analysis and data base searches revealed matches of VL43
      responsive proteins to an endochitinase, a peroxidase, a PR-4 protein and a beta
      1,3-glucanase. In xylem sap three up-regulated proteins were found of which two
      were identified as PR-4 and beta-1,3-glucanase. Xylem sap of infected plants
      inhibited the growth of V. longisporum. CONCLUSION: V. longisporum infection did
      not result in drought stress or nutrient limitations. Stunting and mild chlorosis
      were, therefore, not consequences of insufficient water and nutrient supply due
      to VL43-caused xylem obstruction. A distinct array of extracellular PR-proteins
      was activated that might have limited Verticillium spreading above the hypocotyl.
      In silico analysis suggested that ethylene was involved in up-regulating VL43
      responsive proteins.

PMID- 19094242
TI  - CLOCK expression identifies developing circadian oscillator neurons in the brains
      of Drosophila embryos.
AB  - BACKGROUND: The Drosophila circadian oscillator is composed of transcriptional
      feedback loops in which CLOCK-CYCLE (CLK-CYC) heterodimers activate their
      feedback regulators period (per) and timeless (tim) via E-box mediated
      transcription. These feedback loop oscillators are present in distinct clusters
      of dorsal and lateral neurons in the adult brain, but how this pattern of
      expression is established during development is not known. Since CLK is required
      to initiate feedback loop function, defining the pattern of CLK expression in
      embryos and larvae will shed light on oscillator neuron development. RESULTS: A
      novel CLK antiserum is used to show that CLK expression in the larval CNS and
      adult brain is limited to circadian oscillator cells. CLK is initially expressed
      in presumptive small ventral lateral neurons (s-LNvs), dorsal neurons 2 s (DN2s),
      and dorsal neuron 1 s (DN1s) at embryonic stage (ES) 16, and this CLK expression
      pattern persists through larval development. PER then accumulates in all CLK
      expressing cells except presumptive DN2s during late ES 16 and ES 17, consistent
      with the delayed accumulation of PER in adult oscillator neurons and antiphase
      cycling of PER in larval DN2s. PER is also expressed in non-CLK-expressing cells
      in the embryonic CNS starting at ES 12. Although PER expression in CLK-negative
      cells continues in ClkJrk embryos, PER expression in cells that co-express PER
      and CLK is eliminated. CONCLUSION: These data demonstrate that brain oscillator
      neurons begin development during embryogenesis, that PER expression in non
      oscillator cells is CLK-independent, and that oscillator phase is an intrinsic
      characteristic of brain oscillator neurons. These results define the temporal and
      spatial coordinates of factors that initiate Clk expression, imply that circadian
      photoreceptors are not activated until the end of embryogenesis, and suggest that
      PER functions in a different capacity before oscillator cell development is
      initiated.

PMID- 19094245
TI  - Editorial: food choice and the control of food intake.

PMID- 19094243
TI  - Polymorphism +17 C/G in matrix metalloprotease MMP8 decreases lung cancer risk.
AB  - BACKGROUND: Matrix metalloproteases (MMPs) constitute a family of enzymes capable
      of degrading different components of the extracellular matrix and are implicated
      in the invasion of tumor cells through the basement membrane. Polymorphisms in
      MMP genes may result in changes in the expression of MMPs being associated with
      the development and progression of cancer. We have investigated the association
      between three polymorphisms (-1607 1G/2G, +17 C/G and -77 A/G) in the human
      collagenases MMP1, MMP8 and MMP13 and the risk of development or progression of
      lung cancer. METHODS: A hospital-based case-control study was designed including
      501 lung cancer patients and 510 controls matched. Genotypes were determined by
      PCR-RFLP. Results were analyzed using unconditional logistic regression, Cox's
      proportional hazard regression, and the Kaplan-Meier method. RESULTS: The MMP1
      and MMP13 promoter polymorphisms were not associated with lung cancer risk, while
      the C/G polymorphism in MMP8 was associated with a statistically significant
      decreased risk of developing lung cancer (ORadj = 0.65; 95%CI = 0.45-0.93). The
      Kaplan-Meier analysis showed that the polymorphisms in MMP1, MMP8 and MMP13 not
      seem to modify the overall survival. Multivariate analysis revealed that MMP1,
      MMP8 and MMP13 polymorphisms are not independent prognostic factors for overall
      survival. CONCLUSION: This study suggests that the polymorphism in MMP8 is
      associated with a decreased lung cancer risk, which can be used as a prognostic
      marker in lung cancer.

PMID- 19094246
TI  - Perspectives on ruminant nutrition and metabolism I. Metabolism in the rumen.
AB  - Advances in knowledge of ruminant nutrition and metabolism during the second half
      of the twentieth century have been reviewed. Part I is concerned with metabolism
      in the rumen: Part II discusses utilization of nutrients absorbed from the rumen
      and lower tract to support growth and reproduction. The time frame was prompted
      by the crucial advances in ruminant physiology which arose from the work of Sir
      Jospeh Barcroft and his colleagues at Cambridge in the 1940s and 50s, and by the
      brilliant studies of Robert Hungate on rumen microbiology at much the same time.
      In reviewing the growth of knowledge of the role of bacteria, protozoa, fungi and
      bacteriophages in the rumen, outstanding developments have included the
      identification and characterization of fungi and the recognition that the
      utilization of polysaccharides in the rumen is accomplished by the sequential
      activities of consortia of rumen microorganisms. The role of protozoa is
      discussed in relation to the long standing debate on whether or not the removal
      of protozoa (defaunation) improves the efficiency of ruminant production. In
      relation to nitrogen (N) metabolism, the predation of bacteria by protozoa
      increases protein turnover in the rumen and reduces the efficiency of microbial
      protein production. This may account for the beneficial effects of defaunation
      where dietary N intakes are low and possibly rate limiting for growth and
      production. Current approaches to the measurement of rates of production of short
      chain fatty acids (SCFA) in the rumen based on the mathematical modelling of
      isotope dilution data are outlined. The absorption of SCFA from the rumen and
      hindgut is primarily a passive permeation process. The role of microorganisms in
      N metabolism in the rumen has been discussed in relation to ammonia and urea
      interrelationships and to current inadequacies in the measurement of both protein
      degradation in the rumen and microbial protein synthesis. The growth of knowledge
      of digestion and absorption of dietary lipids has been reviewed with emphasis on
      the antimicrobial activity of lipids and the biohydrogenation of unsaturated
      fatty acids. The protection of unsaturated dietary fats from ruminal
      biohydrogenation is an approach to the manipulation of the fatty acid composition
      of meat and dairy products. Discussion of the production of toxins in the rumen
      and the role of microorganisms in detoxification has focused on the metabolism of
      oxalate, nitrate, mycotoxins, saponins and the amino acid mimosine. Mimosine
      occurs in the tropical shrub leucaena, which is toxic to cattle in Australia but
      not in Hawaii. Tolerance to leucaena stems from the presence of a bacterium found
      in the rumen of Hawaiian cattle, which when transferred to Australian cattle
      survives and confers protection from mimosine. The genetic modification of rumen
      microorganisms to improve their capacity to ultilize nutrients or to detoxify
      antinutritive factors is an attractive strategy which has been pursued with
      outstanding success in the case of fluoroacetate. A common rumen bacterium has
      been genetically modified to express the enzyme fluoroacetate dehalogenase. The
      modified organism has been shown to survive in the rumen at metabolically
      significant levels and to confer substantial protection from fluoroacetate
      poisoning.

PMID- 19094244
TI  - A systematic review and meta-analysis of the effects of clinical pathways on
      length of stay, hospital costs and patient outcomes.
AB  - BACKGROUND: To perform a systematic review about the effect of using clinical
      pathways on length of stay (LOS), hospital costs and patient outcomes. To provide
      a framework for local healthcare organisations considering the effectiveness of
      clinical pathways as a patient management strategy. METHODS: As participants, we
      considered hospitalized children and adults of every age and indication whose
      treatment involved the management strategy "clinical pathways". We include only
      randomised controlled trials (RCT) and controlled clinical trials (CCT), not
      restricted by language or country of publication. Single measures of continuous
      and dichotomous study outcomes were extracted from each study. Separate analyses
      were done in order to compare effects of clinical pathways on length of stay
      (LOS), hospital costs and patient outcomes. A random effects meta-analysis was
      performed with untransformed and log transformed outcomes. RESULTS: In total 17
      trials met inclusion criteria, representing 4,070 patients. The quality of the
      included studies was moderate and studies reporting economic data can be
      described by a very limited scope of evaluation. In general, the majority of
      studies reporting economic data (LOS and hospital costs) showed a positive
      impact. Out of 16 reporting effects on LOS, 12 found significant shortening.
      Furthermore, in a subgroup-analysis, clinical pathways for invasive procedures
      showed a stronger LOS reduction (weighted mean difference (WMD) -2.5 days versus 
      0.8 days)).There was no evidence of differences in readmission to hospitals or in
      hospital complications. The overall Odds Ratio (OR) for re-admission was 1.1 (95%
      CI: 0.57 to 2.08) and for in-hospital complications, the overall OR was 0.7 (95%
      CI: 0.49 to 1.0). Six studies examined costs, and four showed significantly lower
      costs for the pathway group. However, heterogeneity between studies reporting on
      LOS and cost effects was substantial. CONCLUSION: As a result of the relatively
      small number of studies meeting inclusion criteria, this evidence base is not
      conclusive enough to provide a replicable framework for all pathway strategies.
      Considering the clinical areas for implementation, clinical pathways seem to be
      effective especially for invasive care. When implementing clinical pathways, the
      decision makers need to consider the benefits and costs under different
      circumstances (e.g. market forces).

PMID- 19094247
TI  - Self-organization of foraging behaviour: from simplicity to complexity without
      goals.
AB  - A herbivore faces challenges while foraging-ongoing changes in its physiological
      condition along with variation in the nutrient and toxin concentrations of foods,
      spatially and temporally-that make selecting a nutritious diet a vital affair.
      Foraging behaviours arise from simple rules that operate across levels of
      resolution from cells and organs to individuals and their interactions with
      social and physical environments. At all these levels, behaviour is a function of
      its consequences: a behaviour operating on the environment to induce changes is
      itself changed by those events. Thus, behaviour emerges from its own functioning
      behaviour self-organizes-not from that of its surroundings. This ostensible
      autonomy notwith-standing, no self-organizing system (cell, organ, or individual)
      is independent of its environs because existence consists of an ongoing exchange
      of energy and matter. According to this view, the notion of cause and effect is
      replaced with functional relationships between behaviours and environmental
      consequences. Changes in physical environments alter the distribution, abundance,
      nutritional, and toxicological characteristics of plants, which affect food
      preference. Social interactions early in life influence behaviour in various
      ways: animals prefer familiar foods and environments, and they prefer to be with
      companions. Animals in unfamiliar environments often walk farther, ingest less
      food, and suffer more from malnutrition and toxicity than animals in familiar
      environments. An individual's food preferences-and its ability to discriminate
      familiar from novel foods-arise from the functional integration of sensory
      (smell, taste, texture) and postingestive (effects of nutrients and toxins on
      chemo-, osmo-, and mechano-receptors) effects. The ability to discriminate among
      foods is critical for survival: all problems with poisonous plants are due to an
      inability to discriminate or a lack of alternatives. Animals eat a variety of
      foods as a result of nearing or exceeding tolerance limits for sensory and
      postingestive effects unique to each food. After eating any food too frequently
      or excessively, the likelihood increases that animals will eat alternative foods
      owing to exceeding sensory-, nutrient-, and toxin-specific tolerance limits.
      Cyclic patterns of intake of a variety of foods reflect seemingly chaotic
      interactions among flavours, nutrients, and toxins interacting along continua.

PMID- 19094248
TI  - Does the study of feeding behaviour benefit from a teleonomic framework?
AB  - In this paper we respond to the criticisms of Provenza et al. (1998) that our
      framework of learning and feeding motivation (Day et al. 1998) resorts to higher
      order goals, which cannot be falsified by experimentation. We assert that in
      order to be able to predict the feeding behaviour of animals we first need to
      understand what they are trying to achieve (i.e. invoke teleonomy). We then
      detail our framework in such terms that one could envisage experiments that could
      quantitatively test its predictions. We contend that the framework of 'the self
      organization of behaviour' proposed by Provenza et al. (1998) cannot lead to such
      quantitative predictions, since it is invoked to describe feeding behaviour of
      animals a posteriori. It is our own desire, by contrast, to assess feeding
      behaviour a priori, which leads us to propose and defend our framework of
      learning and feeding motivation.

PMID- 19094249
TI  - Assessing dietary intake: Who, what and why of under-reporting.
AB  - Under-reporting of food intake is one of the fundamental obstacles preventing the
      collection of accurate habitual dietary intake data. The prevalence of under
      reporting in large nutritional surveys ranges from 18 to 54% of the whole sample,
      but can be as high as 70% in particular subgroups. This wide variation between
      studies is partly due to different criteria used to identify under-reporters and
      also to non-uniformity of under-reporting across populations. The most consistent
      differences found are between men and women and between groups differing in body
      mass index. Women are more likely to under-report than men, and under-reporting
      is more common among overweight and obese individuals. Other associated
      characteristics, for which there is less consistent evidence, include age,
      smoking habits, level of education, social class, physical activity and dietary
      restraint. Determining whether under-reporting is specific to macronutrients or
      food is problematic, as most methods identify only low energy intakes. Studies
      that have attempted to measure under-reporting specific to macronutrients express
      nutrients as percentage of energy and have tended to find carbohydrate under
      reported and protein over-reported. However, care must be taken when interpreting
      these results, especially when data are expressed as percentages. A logical
      conclusion is that food items with a negative health image (e.g. cakes, sweets,
      confectionery) are more likely to be under-reported, whereas those with a
      positive health image are more likely to be over-reported (e.g. fruits and
      vegetables). This also suggests that dietary fat is likely to be under-reported.
      However, it is necessary to distinguish between under-reporting and genuine under
      eating for the duration of data collection. The key to understanding this
      problem, but one that has been widely neglected, concerns the processes that
      cause people to under-report their food intakes. The little work that has been
      done has simply confirmed the complexity of this issue. The importance of
      obtaining accurate estimates of habitual dietary intakes so as to assess health
      correlates of food consumption can be contrasted with the poor quality of data
      collected. This phenomenon should be considered a priority research area.
      Moreover, misreporting is not simply a nutritionist's problem, but requires a
      multidisciplinary approach (including psychology, sociology and physiology) to
      advance the understanding of under-reporting in dietary intake studies.

PMID- 19094250
TI  - Lipids and infant formulas.
AB  - The ultimate goal in the design of infant formula is to achieve the outcome seen
      in breast fed infants. This review of lipids in infant formulas for term infants
      begins by referring to the lipid composition of human milk, and relates that to
      differences in lipid digestion and metabolism which exist between breast fed and
      formula fed infants and which may significantly influence fatty acid
      bioavailability. Recommendations are made for the lipid content and fatty acid
      composition of term infant formulas (especially for lauric, linoleic, alpha
      linolenic, long chain 20 and 22C n-3 and n-6 polyunsaturated fatty acids and the
      trans fatty acids). Further research is required to define more clearly the long
      term nutritional, growth and developmental effects of structured lipids in
      formulas for term infants. More information is required on the differential
      handling of LCPUFA and other fatty acids at the organ and cellular level. There
      is a need for large (multi-centre) randomized studies to determine the short and
      long term functional effects of LCPUFA supplementation. Further research and
      development is required to determine a commercial source of LCPUFA which is safe,
      effective and economic. Further information is required on the short and long
      term effects of cholesterol intake during infancy, and in particular its
      relationship to LCPUFA metabolism. Long term studies should be initiated to
      determine the relationship of infant diet (especially saturated fatty acid and
      cholesterol intake) to the development of cardiovascular disease.

PMID- 19094251
TI  - Dietary triggers in irritable bowel syndrome.
AB  - Irritable bowel syndrome (IBS) is a frequently occurring, benign functional
      gastrointestinal disorder with a complex poorly understood pathology which
      appears to be multifactorial in nature. There is no association with structural
      or biochemical abnormalities in the gastrointestinal tract. Functional variations
      in myoelectrical activity, visceral hypersensitivity and illness behaviours have
      all been observed in patients experimentally. In conjunction with environmental,
      psychological and alimentary factors, these mechanisms have been proposed as the
      major determinants of symptom genesis. Certainly, dietary factors are frequently
      perceived by sufferers as powerful symptom triggers, with many reporting multiple
      food intolerance. Physicians, however, remain divided upon the relevance of food
      to the disorder, with many eschewing a nutritional connection. This is
      unsurprising as, despite much experimental work to determine the clinical
      relevance of food intolerance and allergy to the aetiology of the disorder, the
      vast range of foodstuffs available for testing, inherent procedural problems with
      test foods, methodological insufficiencies and the continually evolving knowledge
      of the disorder, particularly the subgrouping of sufferers, have restricted the
      scientific validity of current findings. At the present time, it is difficult to
      make informed judgement upon the importance of food in IBS, and rigorously
      designed, large scale trials devised in the light of recent knowledge are
      required before conclusions can be drawn.

PMID- 19094252
TI  - Homocysteine as a risk factor for cardiovascular and related disease: nutritional
      implications.
AB  - The objectives were firstly to assess the evidence that homocysteine is a
      significant and independent risk factor for vascular disease with special
      reference to cardiovascular disease, and secondly to evaluate the evidence that a
      food staple fortified with folic acid will reduce this problem on a population
      basis. The structure of plasma homocysteine (tHcy) is described. Homocysteine, a
      highly reactive compound, is synthesized from the amino acid, methionine, and is
      metabolized by two pathways, the catabolic transsulphuration route via
      cystathionine beta-synthase (EC 4.2.1.22) and the remethylation path using 5
      methyltetrahy-drofolate polyglutamate, the product of 5,10
      methylenetetrahydrofolate reductase (MTHFR; EC 1.1.1.171), via the cobalamin
      dependent enzyme, methionine synthase (MS; EC 2.1.1.13).The mechanisms whereby
      hyper-tHcy is produced include both increased rates of synthesis and decreased
      metabolism. The latter may occur owing to nutritional deficiency of the vitamin
      cofactors which are necessary for the normal function of the metabolic enzymes.
      In particular, folate is required for methylene reductase, pyridoxal phosphate
      for cystathionine synthase and cobalamin for methionine synthase. When these
      vitamins are deficient hyper-tHcy is induced and this occurs especially in the
      elderly. Alternatively, a variant form of methylene reductase has recently been
      described which occurs in nearly 10% of the normal population. This variant is
      associated with hyper-tHcy, especially in situations associated with a low folate
      nutritional status. Meta-analysis of both retrospective case-control studies,
      nested prospective case-control surveys and a secondary trial of mortality in
      postmyocardial infarct patients have shown that the association of hyper-tHcy
      with vascular disease is beyond doubt. This has been further supported by direct
      assessments of the degree of vascular disease in the carotid brachial and aortic
      arteries in relation to tHcy levels. Furthermore, treatment with a cocktail of
      the vitamin cofactors has produced lowering of tHcy levels and regression of the
      vascular disease in the carotid arteries of affected individuals. Suggested
      pathogenic mechanisms in vascular disease induced by hyper-tHcy include vascular
      endothelial cell dysfunction, smooth muscle proliferation and derangements of
      normal intravascular regulation mechanisms. A variety of clinical conditions are
      known to be associated with a high incidence of thromboembolic complications.
      Some of these are associated with hyper-tHcy. Low physiological doses of folic
      acid, as well as pharmocological doses, lower tHcy. However, because of the poor
      bioavailability of food folate (50%) and the considerable chemical instability of
      the naturally occurring reduced forms of folate, in most people it would require
      unacceptably high consumption of green vegetables to accomplish the necessary
      increase in intracellular folate and reduction in tHcy. Accordingly, folic acid,
      the nonreduced synthetic form of the vitamin, which is 100% bioavailable and
      chemically extremely stable, should be added to a food staple such as flour to
      ensure maximum protection for most of the population.

PMID- 19094256
TI  - Vitamin requirements for term infants: considerations for infant formulae.
AB  - OBJECTIVE: To provide the informed health professional with an up to date
      evaluation of the current thinking regarding requirements for vitamins in infant
      feeds. ESTABLISHING CRITERIA FOR ADEQUACY: Vitamin adequacy in the neonate is
      currently defined in terms of circulating levels of a vitamin or of the activity
      of a vitamin dependent enzyme in the erythrocytes. Although these measurements
      have their value there is a need to develop biochemical, physiological or
      clinical markers of well defined specific function. For some vitamins there is a
      risk of deleterious effects of very high intakes: risk of toxicity needs to be
      taken into consideration when making recommendations for inclusion in infant
      formulae. BREAST MILK AS THE 'GOLD STANDARD': Breast milk concentrations of
      vitamins have been used as the criteria of adequate intake by neonates. This may
      not always be justified. Greater consideration needs to be given to differences
      in bioavailability of vitamins from breast milk compared with formula feeds, of
      the influence of season, and of stage of lactation, on the stated composition.
      EXPERIMENTAL APPROACHES: Animal studies have provided limited information
      regarding effects of different levels of intakes on current status indices in the
      neonatal period. There are few reports of randomized controlled studies into the
      effects of different levels of vitamins and these rely heavily on biochemical
      criteria of adequacy. RECENT DEVELOPMENTS: The inclusion of beta-carotene into
      formula feeds for premature babies is an issue of current interest. What is the
      justification for this? Are there potential benefits for the term infant?
      Riboflavin deficiency in the period around weaning may affect the normal
      structural and functional development of the gastrointestinal tract; some of
      these effects may be permanent. RESEARCH TO BE DONE: A greater understanding of
      the absorption and metabolism of vitamins during infancy is required in order to
      help establish dietary requirements. The relative bioavailability of vitamins in
      human milk and formulae needs to be investigated. Criteria for vitamin adequacy
      should be extended to include measures of function. Information regarding the
      conversion factor from tryptophan to niacin in infancy would allow us to set
      niacin requirements with greater confidence. There is a particular lack of
      information about concentrations of biotin and pantothenic acid in breast milk
      and the relative biochemical status of infants receiving breast milk and
      formulae. Benefits of including beta-carotene into infant formulae need to be
      evaluated. The role of individual micronutrients in the structural and functional
      development of the gastrointestinal tract should be explored.

PMID- 19094257
TI  - Health effects of breast feeding for mothers: a critical review.
AB  - Lactation results in a number of physiological adaptations which exert direct
      effects on maternal health, some of which may confer both short and long term
      advantages for breast feeding mothers. Breast feeding in the early postpartum
      period promotes a more rapid return of the uterus to its prepregnant state
      through the actions of oxytocin. Breast feeding may also lead to a more rapid
      return to prepregnancy weight. Among studies that had good data on duration and
      intensity of lactation, the majority show a significant association between
      lactation and weight loss. However, there is no evidence that lactation prevents
      obesity. Lactation also affects glucose and lipid metabolism. The long term
      effects of these adaptations are unknown but may have implications for preventing
      subsequent development of diabetes and heart disease. Lactation delays the return
      of ovulation and significantly reduces fertility during the period of lactational
      amenorrhoea. This process is linked with feeding patterns and may therefore be
      affected by practices such as scheduled feedings and the timing of introduction
      of complementary foods. While the evidence from epidemiologic studies is mixed,
      several large studies have shown that extended lactation is associated with
      reduced risk of premenopausal breast, ovarian and endometrial cancers. Although
      bone mineralization declines during lactation, repletion takes place after
      weaning. As a result, breast feeding does not appear to cause long term depletion
      of bone nor does it increase risk of osteoporosis. Many of the physiological
      effects of lactation are dependent on the stimulation of the hypothalamic
      pituitary axis and milk removal and thus may vary with infant feeding practices.
      Well controlled studies are needed that include detailed information regarding
      infant feeding practices in addition to the total duration of any breast feeding.
      Future feeding recommendations should reflect careful consideration of how such
      practices affect both infant and maternal health.

PMID- 19094258
TI  - Do the changes in energy balance that occur during pregnancy predispose parous
      women to obesity?
AB  - The aim of this review was to re-assess whether the changes in energy balance
      that accompany pregnancy predispose parous women to obesity. A number of cross
      sectional studies have sought to answer this question by examining the
      relationship between parity and maternal body weight. However, these studies were
      unable to control for the large number of sociobehavioural confounders that might
      be responsible for the apparent effect of parity on body weight. Longitudinal
      studies that examine changes in maternal body weight before and after regnancy
      avoid these problems by using each mother as her own control. Nevertheless, these
      studies have to overcome three methodological constraints: They must obtain an
      accurate measure of prepregnant body weight, they must give each mother
      sufficient time to lose any weight retained following delivery, and they must
      take into account the effect of ageing on maternal weight gain during pregnancy
      and the follow-up period. More than 90% of the studies reviewed found body weight
      to be greater after pregnancy than it was before (by 0.2-10.6 kg). and previous
      researchers who have examined the evidence for pregnancy-related weight gains
      suggest that body weight increases by an average of 04-4.8 kg following
      pregnancy. However, only three of the 71 longitudinal studies examined in the
      present review complied with the three methodological criteria. These studies
      concluded that mothers gain, on average, 0.9-3.3 kg more weight following
      pregnancy than nonpregnant controls, and that mean body weight remained 0.4-3.0
      kg higher, even after controlling for a number of sociobehavioural confounders.
      This apparently modest increase in mean maternal body weight for women having one
      or two children conceals the fact that some mothers experience a substantial
      increase in body weight and become obese following pregnancy. It remains unclear
      whether these increases are simply the result of changes in energy metabolism
      during pregnancy and lactation, or whether they are influenced by inherent
      changes in lifestyle that accompany pregnancy and motherhood. Understanding the
      relative importance of these alternatives might help to explain the aetiology of
      maternal obesity."Clover was a stout motherly mare approaching middle life, who
      had never quite got her figure back after her fourth foal"George Well (1945)
      Animal Farm. London: Secker and Warburg.

PMID- 19094259
TI  - The principles, practices and some future applications of near infrared
      spectroscopy for predicting the nutritive value of foods for animals and humans.
AB  - The current application and future potential of near infrared (NIR) spectroscopy
      in the evaluation of foods for domesticated animals and humans is enormous. Where
      used, NIR spectroscopy has revolutionized the analysis and nutritional evaluation
      of animal feeds and human foods by providing a rapid means of examination. The
      availability of accurate and rapid methods of evaluation is becoming increasingly
      important to meet the nutritional requirements of animals for meat, milk, wool
      and egg production. This is essential for efficient and economic animal
      production, to maintain animal health and to minimize environmental impact.
      Accurate evaluation methods are also needed in relation to national and
      international legislation that regulates the circulation, trade and inspection of
      foods and feeds, aids effective functioning of the market and guards the safety
      of animals and humans. The aim of this review is to outline the theory and
      principles of NIR spectroscopy and to focus primarily on its application in the
      field of animal nutrition. The vital role NIR spectroscopy is playing in the
      prediction of biologically meaningful feed characteristics, including data
      derived in vivo, is demonstrated particularly through its application to forage
      evaluation, but also in the examination of raw materials and compound feeds.
      While the applications of NIR spectroscopy to different foods and drinks are
      extensive, this review gives an overview only of selected reported applications
      including its use for predicting nutritive value (mainly water, protein, fat,
      sucrose and starch content), monitoring food processing and for food
      authentication. The review provides clear evidence that the future application of
      NIR spectroscopy will undoubtedly increase, playing a vital role in the
      authentication of the quality and origin of foods and feeds and enabling the
      complex methods of feed evaluation required in the future to be put into
      widespread use.

PMID- 19094260
TI  - Diet and haemostatic processes.
AB  - Diet plays an important role in the primary and secondary prevention of
      cardiovascular disease. The growing perception that abnormal haemostatic
      processes of coagulation, platelet aggregation and fibrinolysis contribute to
      cardiovascular disease aetiology motivated this review on the relationships of
      diet, specific foods and nutrients with haemostatic function. Functional
      endpoints that reflect the function and status of some of these processes and
      which can be measured in dietary trials are identified. The effects of energy
      intake and expenditure, alcohol, total fat and specific fatty acids, non-starch
      polysaccharides (dietary fibre), antioxidant nutrients and some foods on a
      variety of haemostatic markers are reviewed. The results indicate that the
      prudent low-fat, high-fibre diet and maintenance of ideal body weight recommended
      to protect against and treat hyperlipidaemia and coronary heart disease will also
      benefit haemostatic profiles. It is concluded that more research on specific
      effects is needed for improved recommendations on a population level for
      prevention of cardiovascular disease.

PMID- 19094261
TI  - Lactose digestion and maldigestion: implications for dietary habits in developing
      countries.
AB  - Milk is an important source of high quality protein, energy, calcium, potassium,
      phosphorus and riboflavin. It also has good functional properties and a highly
      acceptable taste, making milk a good alternative for the nutrition of children
      and for food programmes in developing countries. However, in some instances it
      has been advocated that milk or milk based products might not be appropriate for
      nutritional support, given the high prevalence of lactose intolerance among
      populations in those countries. After reviewing studies in different regions of
      the world it is concluded that: 1. Prevalence of lactose maldigestion in children
      and adults is significantly reduced, to less than half in most studies, when
      assessed with a dose of milk similar to that normally taken in the diet, as
      distinct from a large dose of lactose used in the lactose tolerance test. 2.
      Lactose intolerance as a result of consuming a glass of milk occurs only in a
      small proportion (about 30% in most studies) of lactose maldigesters. Even this
      small group can ingest smaller amounts of milk without adverse symptoms and there
      is good evidence that colonic metabolism in these people adapts to the presence
      of lactose to reduce or eliminate adverse symptoms. 3. Lactose maldigestion and
      intolerance in children in developing countries is more likely to exist in
      association with gastrointestinal damage associated with diarrhoea, malnutrition
      and/or infection. 4. There is no evidence to support a reduction or elimination
      of milk intake for people in developing countries because of lactose maldigestion
      or intolerance.

PMID- 19094262
TI  - Integrative models of nutrient balancing: application to insects and vertebrates.
AB  - We present and apply to data for insects, chickens and rats a conceptual and
      experimental framework for studying nutrition as a multi-dimensional phenomenon.
      The framework enables the unification within a single geometrical model of
      several nutritionally relevant measures, including: the optimal balance and
      amounts of nutrients required by an animal in a given time (the intake target),
      the animal's current state in relation to these requirements, available foods,
      the amounts of ingested nutrients which are retained and eliminated, and animal
      performance. Animals given a nutritionally balanced food, or two or more
      imbalanced but complementary foods, can satisfy their nutrient requirements, and
      hence optimize performance. However, animals eating noncomplementary imbalanced
      foods must decide on a suitable compromise between overingesting some nutrients
      and underingesting others. The geometrical models provide a means of measuring
      nutritional targets and rules of compromise, and comparing these among different
      animals and within similar animals at different developmental stages or in
      different environments. They also provide a framework for designing and
      interpreting experiments on the regulatory and metabolic mechanisms underlying
      nutritional homeostasis.

PMID- 19094263
TI  - Nutritional implications of resistant starch.

PMID- 19094264
TI  - The nutritional challenges in the new South Africa.

PMID- 19094265
TI  - Protein requirements of older individuals.

PMID- 19094266
TI  - Health advantages of breast feeding for infants: a critical review.

PMID- 19094267
TI  - Bowel function, food intake and the menstrual cycle.

PMID- 19094268
TI  - Nutrition-environment interactions in pregnancy.

PMID- 19094269
TI  - A review of recent research on nutrition and metabolism in the athletic horse.

PMID- 19094270
TI  - Antioxidant nutrients in pregnancy: a systematic review of the literature.

PMID- 19094271
TI  - Epidemiology and mechanisms relating diet to risk of colorectal cancer.

PMID- 19094272
TI  - Effects of Dietary Fat on Cholesterol Metabolism: Regulation of Plasma LDL
      Concentrations.

PMID- 19094273
TI  - Dietary Fatty acids with trans unsaturation.

PMID- 19094274
TI  - Iron deficiency alleviation in developing countries.

PMID- 19094275
TI  - Bioavailability of minerals and trace elements.

PMID- 19094276
TI  - Editorial.

PMID- 19094277
TI  - Influence of dietary Fatty acids on the atherogenic lipoprotein phenotype.

PMID- 19094278
TI  - Molecular biology of intestinal glucose transport.

PMID- 19094279
TI  - Novel substrates to maintain gut integrity.

PMID- 19094280
TI  - Nutrient regulation of skeletal muscle protein metabolism in animals. The
      involvement of hormones and substrates.

PMID- 19094281
TI  - A protein-stat mechanism for regulation of growth and maintenance of the lean
      body mass.

PMID- 19094282
TI  - Dietary effects on ruminant livestock reproduction with particular reference to
      protein.

PMID- 19094283
TI  - Water in pig nutrition: physiology, allowances and environmental implications.

PMID- 19094284
TI  - Measuring dietary exposure in nutritional epidemiological studies.

PMID- 19094285
TI  - The epidemiology of vegetarianism and health.

PMID- 19094286
TI  - The relationship between diet, nutrition and dental health: an overview and
      update for the 90s.

PMID- 19094287
TI  - Appetite control and energy (fuel) balance.

PMID- 19094288
TI  - Food, mood and appetite.

PMID- 19094289
TI  - The intake of selected minerals and trace elements in European countries.

PMID- 19094290
TI  - The composition of human milk as a model for the design of infant formulas:
      recent findings and possible applications.

PMID- 19094292
TI  - Physical activity, not diet, should be the focus of measures for the primary
      prevention of cardiovascular disease.

PMID- 19094291
TI  - Feto-maternal interaction of antibody and antigen transfer, immunity and allergy
      development.

PMID- 19094293
TI  - Nutrition, physical activity and bone health in women.

PMID- 19094294
TI  - Human bioavailability of vitamins.

PMID- 19094295
TI  - Biology of zinc and biological value of dietary organic zinc complexes and
      chelates.

PMID- 19094296
TI  - Zinc nutrition in developing countries.

PMID- 19094297
TI  - Anticarcinogenic factors in plant foods: a new class of nutrients?

PMID- 19094298
TI  - Glucosinolates and glucosinolate derivatives: implications for protection against
      chemical carcinogenesis.

PMID- 19094300
TI  - Self-experimentation in nutrition research.

PMID- 19094299
TI  - Nutritional influences on interactions between bacteria and the small intestinal
      mucosa.

PMID- 19094301
TI  - The use and construction of anthropometric growth reference standards.

PMID- 19094302
TI  - An appraisal of the adequacy of dietary mineral intakes in developing countries
      for bone growth and development in children.

PMID- 19094303
TI  - Methods for studying mineral and trace element absorption in humans using stable
      isotopes.

PMID- 19094304
TI  - Essential and conditionally-essential nutrients in clinical nutrition.

PMID- 19094305
TI  - Cassava (Manihot esculenta crantz) in the aetiology of kwashiorkor.

PMID- 19094307
TI  - Postprandial lipoprotein metabolism.

PMID- 19094306
TI  - Effects of diet and physical activity on adiposity and body fat distribution:
      implications for the prevention of cardiovascular disease.

PMID- 19094308
TI  - Nutritional implications of gastrointestinal and liver metabolism in ruminants.

PMID- 19094309
TI  - Tannins in feedstuffs for simple-stomached animals.

PMID- 19094310
TI  - Availability and utilization of amino acids for growing pigs.

PMID- 19094311
TI  - Nutritional value of grain legumes for ruminants.

PMID- 19094313
TI  - The energy values of dietary fibre and sugar alcohols for man.

PMID- 19094312
TI  - Barley beta-glucan: an antinutritional factor in poultry feeding.

PMID- 19094314
TI  - Interrelationships between the gastrointestinal microflora and non-nutrient
      components of the diet.

PMID- 19094315
TI  - Nutrition and multiple organ failure.

PMID- 19094316
TI  - The low birth weight infant and parenteral nutrition.

PMID- 19094317
TI  - Cigarette smoking and food and nutrient intakes in relation to coronary heart
      disease.

PMID- 19094318
TI  - Alcohol consumption in the elderly.

PMID- 19094319
TI  - Trace element nutrition and bone metabolism.

PMID- 19094320
TI  - Iron deficiency and the measurement of iron status.

PMID- 19094321
TI  - Food sensitivity and the nervous system: hyperactivity, addiction and criminal
      behaviour.

PMID- 19094322
TI  - The inter-organ flux of substrates in fed and fasted man, as indicated by arterio
      venous balance studies.

PMID- 19094323
TI  - Maternal vitamin nutrition and malformations of the neural tube.

PMID- 19094324
TI  - Nutrition in cystic fibrosis.

PMID- 19094325
TI  - Intra-household food and nutrient allocation.

PMID- 19094326
TI  - Nutrition and immunity in the elderly.

PMID- 19094327
TI  - The influence of legume seeds on human plasma lipid concentrations.

PMID- 19094328
TI  - Comparative aspects of gastrointestinal phosphorus metabolism.

PMID- 19094329
TI  - Critical evaluation of in vitro methods for estimating digestibility in simple
      stomach animals.

PMID- 19094330
TI  - Nutritional Deficiencies and Children's Behaviour and Mental Development.

PMID- 19094331
TI  - The contribution of weaning foods to protein-energy malnutrition.

PMID- 19094332
TI  - Physiological mechanisms in the adaptive response of metabolic rates to energy
      restriction.

PMID- 19094333
TI  - Nutrition and cancer - some biochemical mechanisms.

PMID- 19094334
TI  - Sodium-calcium inter-relationships with specific reference to osteoporosis.

PMID- 19094336
TI  - Growth hormone secretion: its regulation and the influence of nutritional
      factors.

PMID- 19094335
TI  - Nutritional aspects of aluminium toxicity.

PMID- 19094337
TI  - The nutritional regulation of growth hormone action.

PMID- 19094338
TI  - Nutrition and cytokine action.

PMID- 19094339
TI  - Nutrition and whole-body protein turnover in the chicken in relation to Mammalian
      species.

PMID- 19094340
TI  - Nutritional regulation of gastric secretion, digestion and emptying.

PMID- 19094341
TI  - Nutrition in the reproduction of farm animals.

PMID- 19094342
TI  - Factors affecting the utilization of 'poor-quality' forages by ruminants
      particularly under tropical conditions.

PMID- 19094343
TI  - Nutrition in renal failure.

PMID- 19094344
TI  - Vitamin A, immunity and infection.

PMID- 19094345
TI  - Non-haematological aspects of iron nutrition.

PMID- 19094346
TI  - Oxidants, antioxidants and cardiovascular disease.

PMID- 19094347
TI  - Dietary fat and plasma lipids.

PMID- 19094348
TI  - Peptides in human nutrition.

PMID- 19094349
TI  - Human amino acid and protein requirements: current dilemmas and uncertainties.

PMID- 19094350
TI  - Dietary fibre and mineral bioavailability.

PMID- 19094351
TI  - Physiological aspects of the requirement for sodium in mammals.

PMID- 19094352
TI  - Nutritional regulation of pancreatic and biliary secretions.

PMID- 19094353
TI  - Biochemical bases needed for the mathematical representation of whole animal
      metabolism.

PMID- 19094354
TI  - Thiamin and niacin in ruminant nutrition.

PMID- 19094355
TI  - Effects of gastrointestinal helminth parasites on ruminant nutrition.

PMID- 19094356
TI  - Cows' milk intolerance.

PMID- 19094357
TI  - Zinc in human nutrition.

PMID- 19094358
TI  - Early biochemical defects caused by dietary trace element deficiencies.

PMID- 19094359
TI  - Essential and trans-Fatty acids in nutrition.

PMID- 19094360
TI  - Nutrient regulation of the enteroinsular axis and insulin secretion.

PMID- 19094361
TI  - Taurine nutrition.

PMID- 19094362
TI  - Body composition measurements for nutrition research.

PMID- 19094363
TI  - Sensory influences on salt, sugar and fat intake.

PMID- 19094364
TI  - Metabolic aspects of the regulation of voluntary food intake and appetite.

PMID- 19094365
TI  - Hormonal control of gut motility in ruminants and non-ruminants and its
      nutritional implications.

PMID- 19094366
TI  - The nutritional implications of differential passage of particles through the
      ruminant alimentary tract.

PMID- 19094367
TI  - Nutritional effects of tannins in animal feeds.

PMID- 19094368
TI  - Nutritional constraints to lean tissue accretion in farm animals.

PMID- 19094369
TI  - The nutrition of fish: the developing scene.

PMID- 19094371
TI  - Does context or color improve object recognition in patients with low vision?
AB  - Most studies on people with age-related macular degeneration (AMD) have been
      focused on investigations of low-level processes with simple stimuli like
      gratings, letters, and in perception of isolated faces or objects. We
      investigated the ability of people with low vision to analyze more complex
      stimuli like photographs of natural scenes. Fifteen participants with AMD and low
      vision (acuity on the better eye <20/200) and 11 normally sighted age-matched
      controls took part in the study. They were presented with photographs of either
      colored or achromatic gray level scenes in one condition and with photographs of
      natural scenes versus isolated objects extracted from these scenes in another
      condition. The photographs were centrally displayed for 300 ms. In both
      conditions, observers were instructed to press a key when they saw a predefined
      target (a face or an animal). The target was present in half of the trials. Color
      facilitated performance in people with low vision, while equivalent performance
      was found for colored and achromatic pictures in normally sighted participants.
      Isolated objects were categorized more accurately than objects in scenes in
      people with low vision. No difference was found for normally sighted observers.
      The results suggest that spatial properties that facilitate image segmentation
      (e.g., color and reduced crowding) help object perception in people with low
      vision.

PMID- 19094370
TI  - Two types of cone bipolar cells express voltage-gated Na+ channels in the rat
      retina.
AB  - Two groups of retinal cone bipolar cells (CBCs) in rats were found to express
      voltage-gated Na+ channels. The axon terminals of the first group stratify in
      sublamina 2 of the inner plexiform layer (IPL) and partially overlap with the OFF
      cholinergic band. This group was identified as type 3 CBCs. The axon terminals of
      the second group stratify in sublamina 3 of the IPL, slightly distal to the ON
      cholinergic band. Cells of this second group resemble type 5 CBCs. In addition,
      we observed another group of ON-type CBCs with terminal stratification similar to
      that of the second group. However, this latter group did not show any Na+
      current, instead exhibiting a large hyperpolarization-activated cyclic nucleotide
      gated cation current, suggesting the existence of two subclasses of
      physiologically distinct type 5 CBCs. Both groups of Na+-expressing bipolar cells
      were capable of generating a rapid tetrodotoxin-sensitive action potential as
      revealed by current injection. Multiple spike-like potentials were also observed
      in some of these cells. Results of this study provide valuable insights into the
      function of voltage-gated Na+ channels of retinal bipolar cells in retinal
      processing.

PMID- 19094373
TI  - Introduction to the supplement: Controversies and challenges of tetralogy of
      fallot and other challenges facing paediatric cardiovascular practitioners and
      their patients.

PMID- 19094374
TI  - The early history of surgery for patients with tetralogy of Fallot.

PMID- 19094375
TI  - The anatomy of tetralogy of Fallot with pulmonary stenosis.

PMID- 19094376
TI  - Echocardiography in tetralogy of Fallot.

PMID- 19094377
TI  - Surgical correction for patients with tetralogy of Fallot and common
      atrioventricular junction.

PMID- 19094378
TI  - Anatomy, echocardiography, and surgical approach to double outlet right
      ventricle.

PMID- 19094379
TI  - Anatomy, morphogenesis, diagnosis, management, and outcomes for neonates with
      common arterial trunk.

PMID- 19094380
TI  - Assessment and management of the failing heart in children.

PMID- 19094381
TI  - Current challenges in cardiac intensive care: optimal strategies for mechanical
      ventilation and timing of extubation.

PMID- 19094385
TI  - Recent advances in nanomaterial plasmonics: fundamental studies and applications.

PMID- 19094387
TI  - Correction of ultraviolet-induced fluorescence spectra for the examination of
      polychromy.
AB  - Ultraviolet-induced fluorescence spectroscopy is a commonly used technique for
      the characterization and identification of painting materials, such as organic
      binders and colorants. Its interpretation is strictly connected to both the
      experimental setup and an understanding of the physical and chemical interactions
      among materials in paint layers, which are commonly composed of a fluorescent
      organic binder and a pigment. When irradiated with ultraviolet radiation, the
      light emitted by fluorophores present in the organic binder undergoes several
      types of interactions, in particular scattering and absorption by neighboring
      pigmented particles and auto-absorption. As a result of scattering and absorption
      phenomena, the emission spectrum is deformed according to the physical properties
      of the surrounding pigmented particles. This can lead to shifts of the emission
      maxima and/or to the formation of apparent new emission bands. The extent of the
      modifications to the emission spectra, caused by auto-absorption and selective
      absorption phenomena, may lead to the erroneous characterization or
      identification of the fluorescent materials. As a consequence, the interpretation
      of the emission signal can be greatly compromised. A correction based on the
      Kubelka-Munk theory is proposed to evaluate the extent of the spectral distortion
      and is assessed on modern replicas of wall paintings of known composition.
      Although the model cannot be applied to all cases, qualitative distinctions
      between real and apparent emissions are achieved.

PMID- 19094386
TI  - The tendon-to-bone transition of the rotator cuff: a preliminary Raman
      spectroscopic study documenting the gradual mineralization across the insertion
      in rat tissue samples.
AB  - We applied Raman spectroscopy to monitor the distribution of mineral and the
      degree of mineralization across the tendon-bone insertion site in the shoulders
      of five rats. We acquired Raman spectra from 100 to 4,000 Deltacm(-1) on
      individual 1 microm points across the 120 microm wide transition zone of each
      tissue sample and identified all the peaks detected in pure tendon and in pure
      bone, as well as in the transition zone. The intensity of the 960 Deltacm(-1) P-O
      stretch for apatite (normalized to either the 2,940 Deltacm(-1) C-H stretch or
      the 1,003 Deltacm(-1) C-C stretch for collagen) was used as an indicator of the
      abundance of mineral. We relate the observed histological morphology in the
      tissue thin section with the observed Raman peaks for both the organic component
      (mostly collagen) and the inorganic component (a carbonated form of the mineral
      apatite) and discuss spectroscopic issues related to peak deconvolution and
      quantification of overlapping Raman peaks. We show that the mineral-to-collagen
      ratio at the insertion site increases linearly (R(2) = 0.8 for five samples) over
      the distance of 120 microm from tendon to bone, rather than abruptly, as
      previously inferred from histological observations. In addition, narrowing of the
      960 Deltacm(-1) band across the traverse indicates that the crystalline ordering
      within the apatite increases concomitantly with the degree of mineralization.
      This finding of mineral gradation has important clinical implications and may
      explain why the uninjured tendon-to-bone connection of the rotator cuff can
      sustain very high loads without failure. Our finding is also consistent with
      recent mechanical models and calculations developed to better understand the
      materials properties of this unusually strong interface.

PMID- 19094388
TI  - Molecular hydraulic properties of montmorillonite: a polarized fourier transform
      infrared spectroscopic study.
AB  - Understanding the rates at which fluid flows into clay interlayers at the
      molecular level is fundamental to designing an effective clay barrier system. In
      this work, molecular interactions at the Na-montmorillonite (MMT)-water
      interface, emphasizing the flow properties of the clay interlayer, have been
      studied at the molecular and nanoscale level using polarized Fourier transform
      infrared (FT-IR) spectroscopic and X-ray diffraction (XRD) techniques. Clay-water
      slurries were smeared on inert gold-coated metal substrates for FT-IR experiments
      and slurries were smeared on quartz plates for XRD experiments. By analyzing the
      O-H stretching and H-O-H bending vibrations in clay slurries, it was concluded
      that the molecular behavior of interlayer water is significantly different from
      the molecular behavior of bulk water. With increasing clay-water interaction
      time, it was also seen that the Si-O stretching bands of clay are being
      significantly altered by the water molecules in the interlayer. Using these
      spectroscopic techniques we have estimated the time required for water to flow
      into the clay interlayer. Further, by analyzing the particle size of the clay
      using atomic force microscopy (AFM) imaging, we were able to estimate the flow
      velocity of the water in the clay interlayer. This velocity is found to be 3.23 x
      10(-9) cm/s. This flow velocity was found to be of the same order of magnitude as
      the hydraulic conductivity of smectite-type clay reported elsewhere. Also
      described in this work is the correct positioning of the Si-O out-of-plane
      vibration band of MMT at the two-layer saturation level in the interlayer. This
      band was only observed in p-polarized spectra at 1211 cm(-1). Thus, we attribute
      this band to the Si-O out-of-plane vibration band.

PMID- 19094389
TI  - Multiple peak reference method for polarized Fourier transform infrared
      attenuated total reflection spectroscopy to determine the three-dimensional
      orientation of a uniaxially drawn poly(trimethylene 2,6-naphthalate) film.
AB  - The polarized Fourier transform infrared-attenuated total reflection (FT-IR-ATR)
      technique is a very useful infrared spectroscopic method for characterizing the
      three-dimensional orientation of thick samples, to which the conventional
      transmission FT-IR method cannot easily be applied. To quantitatively analyze
      polarized FT-IR-ATR spectra, the dependence of the optical contact between the
      sample and the ATR crystal during the clamping and reclamping processes must be
      controlled. In this work, a new multiple peak reference (MPR) method is proposed
      and used to carry out a three-dimensional analysis of a poly(trimethylene 2,6
      naphthalate) (PTN) polymer sample. The conventional single peak reference (SPR)
      analysis technique cannot be applied to such a sample due to the lack of an
      established reference peak. A new artificial reference band was generated by the
      MPR method using two different infrared bands, at 1602 cm(-1) and 917 cm(-1), in
      identical spectra with a combination constant of 0.95. The new artificial
      reference band was successfully used to calculate the three-dimensional
      orientation of various infrared bands of a uniaxially drawn PTN film, which has
      not previously been studied by three-dimensional orientation analyses using the
      polarized FT-IR-ATR method.

PMID- 19094391
TI  - Finite element analysis modeling of pulse-laser excited photothermal deflection
      (mirage effect) from aerosols.
AB  - A finite element analysis method for numerical modeling of the photothermal
      deflection spectroscopy of aerosols is presented. The models simulate pulse-laser
      excited photothermal deflection from aerosols collected on a plane surface
      substrate in air medium. The influence of the aerosol and substrate properties on
      the transient photothermal deflection signal is examined. We have previously
      obtained experimental results for photothermal deflection spectrometry of
      aerosols deposited onto a plate from an impactor system (O. O. Dada and S. E.
      Bialkowski, Appl. Spectrosc. 62, 1336 (2008)). This paper supports the validity
      of the experimental results presented in that paper and helps in answering some
      of the questions raised. The modeling results presented here demonstrate that the
      (peak) normalized transient temperature change profile and (peak) normalized
      transient photothermal deflection profile are a good approximation and invariant
      with number of particles, inter-particle distance, and particulate shape, which
      suggests that the photothermal deflection signal amplitude may be calibrated
      linearly with total mass of aerosols and the method could be applied to analysis
      of complex aerosols.

PMID- 19094390
TI  - A mid-infrared flow-through sensor for label-free monitoring of enzyme
      inhibition.
AB  - Label-free monitoring of acetylcholinesterase (AChE) activity was achieved with a
      mid-infrared flow-through sensor. The flow-through sensor comprised agarose
      beads, carrying covalently immobilized AChE, which were placed in a temperature
      controlled (37 degrees C) CaF(2) flow cell with an optical path of 60 mum. The
      sensor was incorporated into a computer-controlled sequential injection (SI)
      system for automated liquid handling. Different mixtures of enzyme substrate
      acetylcholine (ACh) and inhibitor (tacrine) were prepared and fed into the flow
      through sensor. The flow was stopped as soon as the prepared mixtures reached the
      sensor. Enzymatic hydrolysis of ACh by AChE was directly monitored as it took
      place in the flow-through sensor. The inhibition effect of tacrine was calculated
      from the reaction-induced spectral changes, revealing an important decrease in
      the activity of AChE, approaching zero when the inhibitor concentration is high
      enough. The developed mid-infrared flow-through sensor is flexible and can be
      used to study the inhibitor activity of different target molecules as well as
      different enzymes.

PMID- 19094392
TI  - Development of infrared photothermal deflection spectroscopy (mirage effect) for
      analysis of condensed-phase aerosols collected in a micro-orifice uniform deposit
      impactor.
AB  - The potential of mid-infrared photothermal deflection spectrometry for aerosol
      analysis is demonstrated. Ammonium nitrate aerosols are deposited on a flat
      substrate using a micro-orifice uniform deposit impactor (MOUDI). Photothermal
      spectroscopy with optical beam deflection (mirage effect) is used to detect
      deposited aerosols. Photothermal deflection from aerosols is measured by using
      pulsed infrared laser light to heat up aerosols collected on the substrate. The
      deflection signal is obtained by measuring the position of a spot from a beam of
      light as it passes near the heated surface. The results indicate non-rotating
      impaction as the preferred MOUDI impaction method. Energy-dependent photothermal
      measurement shows a linear relationship between signal and laser intensity, and
      no loss of signal with time is observed. The detection limit from the signal-mass
      curve is 7.31 ng. For 30 minutes collection time and 30 L/min flow rate of the
      impactor, the limit of detection in terms of aerosol mass concentration is 0.65
      microg m(-3).

PMID- 19094393
TI  - New technique for the direct analysis of food powders confined in a small hole
      using transversely excited atmospheric CO(2) laser-induced gas plasma.
AB  - Taking advantage of the differences between the interactions of transversely
      excited atmospheric (TEA) CO(2) lasers with metal and with organic powder, a new
      technique for the direct analysis of food powder samples has been developed. In
      this technique, the powder samples were placed into a small hole with a diameter
      of 2 mm and a depth of 3 mm and covered by a metal mesh. The TEA CO(2) laser
      (1500 mJ, 200 ns) was focused on the powder sample surfaces, passing through the
      metal mesh, at atmospheric pressure in nitrogen gas. It is hypothesized that the
      small hole functions to confine the powder particles and suppresses the blowing
      off of sample, while the metal mesh works as the source of electrons to initiate
      the strong gas breakdown plasma. The confined powder particles are then ablated
      by laser irradiation and the ablated particles move into the strong gas breakdown
      plasma region to be atomized and excited; this method cannot be applied for the
      case of Nd:YAG lasers because in such case the metal mesh itself was ablated by
      the laser irradiation. A quantitative analysis of a milk powder sample containing
      different concentrations of Ca was successfully demonstrated, resulting in a good
      linear calibration curve with high precision.

PMID- 19094394
TI  - Sensing of water dissolved in solvents using a 5.629 microm multimode quantum
      cascade laser.
AB  - We report herein the detection of liquid water dissolved in a variety of solvents
      using a thermoelectrically cooled, pulsed, Fabry-Perot quantum cascade laser,
      operating at 5.629 microm at room temperature. The prototype sensor system
      consisted of the laser, a series of off-axis parabolic mirrors, and two mercury
      cadmium telluride detectors. When applied to the detection of water in
      tetrahydrofurane, a limit of detection of 0.85 parts per million was achieved. It
      is envisaged that such a sensor would be well suited to process control
      applications within the pharmaceuticals industry.

PMID- 19094395
TI  - Pressure broadening of H(2)O absorption lines in the 1.3 microm region measured
      by continuous wave-cavity ring-down spectroscopy: application in the trace
      detection of water vapor in N(2), SiH(4), CF(4), and PH(3).
AB  - A continuous wave cavity ring-down (cw-CRD) spectrometer has been developed for
      the measurement of trace levels of water vapor by absorption spectroscopy at
      wavelengths in the vicinity of 1358 nm and 1392 nm. The speed of data acquisition
      and selectivity make cavity ringdown spectroscopy potentially more useful than
      current techniques for measurement of trace water in process gases and vacuum
      environments used for semiconductor manufacture where water vapor contamination
      has a detrimental effect on the final product. The pressure broadening
      coefficients (gamma) for bath gases N(2), air, and Ar and semiconductor process
      gases SiH(4), PH(3), and CF(4) were determined for a range of absorption lines in
      the 2nu(1) and nu(1) + nu(3) bands of H(2)O. For the transitions investigated,
      the concentration of water vapor in the sample gas varied from 1.7 x 10(12) to
      2.9 x 10(15) molecule cm(-3) in N(2) at a total pressure of <10 mbar and was
      mixed with the bath gas of increasing pressure up to approximately 200 mbar. The
      values of gamma quantify the reduction in peak absorption cross-sections with
      bath gas pressure and, thus, their effects on the detection limit of water vapor.
      For a CRD spectrometer with a ring-down time of tau = 12.0 mus measured with a
      precision of 0.6%, detection limits for the measurement of water vapor in 1 atm
      N(2) and of CF(4) were estimated to be 18 and 14 ppbv, respectively. Competing
      absorption by SiH(4) and PH(3) in the 1.3 mum wavelength region results in
      respective detection limits for water vapor of 98 and 319 ppbv (relative to 1
      atm) in 0.2 atm SiH(4) and 0.37 atm PH(3).

PMID- 19094396
TI  - Application of representative layer theory to near-infrared reflectance spectra
      of powdered samples.
AB  - The diffuse reflectance near-infrared (NIR) spectrum of a powdered sample
      includes the contribution of specular and diffuse reflectance, which is a
      function of absorbance and scattering. The fraction of light scattered depends in
      a complex manner on the physical properties of the sample such as particle size,
      refraction index, etc. Several theories to study the dependence of NIR spectra on
      the particle size have been proposed. The best known is the Kubelka-Munk model,
      an approach based on continuous mathematics. Recently Dahm and Dahm put forward
      an alternative method, the representative layer theory (RLT), which uses
      discontinuous mathematics as a basis. This approach can be used to identify and
      disentangle the scattering and absorbance signals as well as their dependence on
      the particle size. The scattering and absorption coefficient of NaCl (a
      nonabsorbing material) and of potassium hydrogen phthalate, KHP (a strong
      absorber), have been estimated through the application of the representative
      layer theory, working on a particle size range from 63 to 450 microm. In both
      samples, the absorption coefficient of the sample (K) remains constant and
      practically independent of the particle size, while the scattering coefficient of
      the sample (S) decreases when the particle diameter increases, becoming stable
      around a diameter of 250 microm.

PMID- 19094397
TI  - Reflectance microspectroscopy of natural rock samples in the visible and near
      infrared.
AB  - We have collected reflectance spectra of various unprocessed rock samples in the
      450-1,650 nm wavelength range with a spatial resolution of 60 and 120 microm
      (diameter) and using three illumination modes. Spectra taken in diffuse
      reflectance (dark field) mode are comparable to those obtained from macroscopic
      measurements and can provide the basis for mineral detection at that spatial
      scale. The spectral discrimination of the dark field mode is demonstrated to be
      consistent with the spatial resolution of the microscope for the samples
      examined. These results support the conclusion that reflectance microspectroscopy
      in the visible and near-infrared regions can be a valuable tool for understanding
      mineral formation at the spatial scale of tens of micrometers.

PMID- 19094398
TI  - Possibilities for using Raman spectroscopy to determine the amount of analyte
      directly from a solid-phase extraction cartridge in water-based applications.
AB  - Raman spectroscopy is occasionally used as a detection technique in liquid
      chromatography. This paper shows that the amount of analyte can also be
      determined directly from a solid-phase extraction cartridge, which eliminates the
      need for solvents in the analysis. Transmission geometry was used in Raman
      probing of the sorbent bed and interferences from the tube material were reduced
      by using quartz glass instead of the commonly used plastic. Bonded-phase silica
      C18 was a test sorbent, and ethylbenzene, as a test analyte, was extracted from
      its water solutions. A detection limit of 3 microg/mL was obtained in the Raman
      calibration by using a univariate method with a CH band of the sorbent ligand as
      an internal standard. This is only an order of magnitude higher than what was
      estimated for liquid chromatography with the same Raman instrument as its
      detector. In addition, an optimal sorbent for each analyte can be chosen more
      freely if there is no need to bother about further elution of the analyte.

PMID- 19094399
TI  - Influences of composition on electroless deposition of silver nanoparticles on
      glass substrates for surface-enhanced Raman scattering measurements.
AB  - A silver-mirror reaction was used to prepare active substrates for surface
      enhanced Raman scattering (SERS). Glass plates were surface treated with a thin
      layer of silver nanoparticles (Ag-NPs). The factors influencing the performance
      of the SERS substrates were systematically studied. Factors included
      concentrations, species of complexing agents, and reducing agents. p
      Nitrothiophenol (pNTP) was used to test the surfaces with Ag-NPs, with the
      observed signals used to compare the performance resulting from different
      reducing and complexing agents. The morphologies of the Ag-NPs formed by
      different reaction conditions were also examined by scanning electron microscope
      (SEM) and correlated with the SERS signals. Reducing agents included
      formaldehyde, sodium tartrate, and several carbohydrates. The results indicate
      that the use of glucose as a reducing agent produced the most suitable Ag-NPs for
      SERS measurements. Complexing agents of ammonia and ethyl amine offered the best
      performances. The optimal concentration of complexing agent was found to be
      approximately six times the concentration of silver ions. With a reaction time of
      2 min, the optimized concentrations of glucose and silver nitrate were 0.5 M and
      50 mM, respectively. In general, the enhancement factor was on the order of 10(5)
      to 10(6) for the substrates prepared in this work.

PMID- 19094400
TI  - Portable equipment for luminescence lifetime measurements on surfaces.
AB  - The prototype of a portable instrument, based on the time-correlated single
      photon counting method, purposely assembled for in situ measurements of
      luminescence lifetimes on artwork surfaces, is here presented. Preliminary tests
      have been carried out using the portable instrument and the results have been
      compared with those obtained using a bench instrument. In this way we have proven
      that the prototype provides lifetime measurements with good precision. It is also
      shown that fluorescence lifetime determinations, coupled with steady-state
      fluorescence spectra, allow the distinguishing, on laboratory samples, of
      different red organic lakes having similar fluorescence spectra, achieving new
      boundaries in the nondestructive diagnosis of artwork materials. The first in
      situ application of the technique on an original work of art, The Book of Kells,
      held at Trinity College Library, Dublin, highlighted the diagnostic potential of
      coupled steady-state and time-resolved luminescence spectroscopy in the
      identification of organic colorants.

PMID- 19094401
TI  - Autumn issue of Informatics in Primary Care: extending our understanding and the
      case for greater research capacity and capability in informatics. Editorial.

PMID- 19094402
TI  - Strategic considerations for improving the quality of eHealth research: we need
      to improve the quality and capacity of academia to undertake informatics
      research.

PMID- 19094403
TI  - Two nations achieve a high level of primary care information technology (IT)
      interoperability: an introduction to a series comparing Denmark and New Zealand's
      IT and health care.

PMID- 19094404
TI  - Adoption of information technology in primary care physician offices in New
      Zealand and Denmark, part 1: healthcare system comparisons.
AB  - Denmark and New Zealand are two small countries whose primary care physicians are
      at the forefront of the use of electronic medical records (EMRs). This is the
      first of a series of five papers which contrasts the health care systems in
      Denmark and New Zealand. Though the delivery of care at the patient level is
      virtually the same in New Zealand and Denmark the way in which the health care is
      financed, administered and managed does vary. This paper highlights the
      differences, particularly in terms of the approaches taken to primary care and
      out-of-office-hours services.

PMID- 19094405
TI  - Adoption of information technology in primary care physician offices in New
      Zealand and Denmark, part 2: historical comparisons.
AB  - This second paper in a series of five looks at how computing in primary care
      began and provides background to the driving forces for automation in Danish and
      New Zealand primary care physician offices. It addresses topics such as
      government funding support, the role of professional colleges and associations,
      peer influence, change management, and comparative cultures. It also highlights
      the power of a unifying organisation and introduces the concept of a Health
      Systems Integrator.

PMID- 19094406
TI  - Needing smart home technologies: the perspectives of older adults in continuing
      care retirement communities.
AB  - BACKGROUND: At present, the vast majority of older adults reside in the
      community. Though many older adults live in their own homes, increasing numbers
      are choosing continuing care retirement communities (CCRCs), which range from
      independent apartments to assisted living and skilled-nursing facilities. With
      predictions of a large increase in the segment of the population aged 65 and
      older, a subsequent increase in demand on CCRCs can be anticipated. With these
      expectations, researchers have begun exploring the use of smart home information
      based technologies in these care facilities to enhance resident quality of life
      and safety, but little evaluation research exists on older adults' acceptance and
      use of these technologies. OBJECTIVE: This study investigated the factors that
      influence the willingness of older adults living in independent and assisted
      living CCRCs to adopt smart home technology. SUBJECTS AND SETTING: Participants
      (n = 14) were recruited from community-dwelling older adults, aged 65 or older,
      living in one of two mid-western US CCRC facilities (independent living and
      assisted living type facilities). METHODS: This study used a qualitative,
      descriptive approach, guided by principles of grounded theory research. Data
      saturation (or when no new themes or issues emerged from group sessions) occurred
      after four focus groups (n = 11 unique respondents) and was confirmed through
      additional individual interviews (n = 3). RESULTS: The findings from this study
      indicate that although privacy can be a barrier for older adults' adoption of
      smart home technology their own perception of their need for the technology can
      override their privacy concerns. CONCLUSIONS: Factors influencing self-perception
      of need for smart home technology, including the influence of primary care
      providers, are presented. Further exploration of the factors influencing older
      adults' perceptions of smart home technology need and the development of
      appropriate interventions is necessary.

PMID- 19094407
TI  - Early experience of the use of short message service (SMS) technology in routine
      clinical care.
AB  - OBJECTIVE: To conduct a technical appraisal and qualitative interviews with short
      message service (SMS--mobile phone text message) users in mainstream health care.
      DESIGN: Observation of service usage followed by in-depth semi-structured
      interviews. SETTING: A National Health Service (NHS) general practice in
      Scotland. PARTICIPANTS: One hundred and eighty patients registered. MAIN OUTCOME
      MEASURES: Service utilisation and patients' views. RESULTS: It was technically
      feasible to open up access to mainstream NHS general practice services using SMS
      for appointment booking, repeat prescription ordering, clinical enquiries and
      remote access to the core clinical summary. CONCLUSION: Patients were able to use
      SMS services responsibly and found automation of prescription ordering
      particularly useful. Service utilisation was modest and did not adversely impact
      on the workload of general practitioners (GPs) or their staff.

PMID- 19094408
TI  - Improving information management in primary care: the proof is in the pudding.
AB  - Generalists in both the USA and UK have been at the forefront of improving
      information management skills, defined here as the abilities required to locate
      and utilise synthesised information for patient care that is accessible, current,
      relevant and valid. Over the past decade, a variety of interventions designed to
      improve knowledge and skills relative to information management has been
      implemented. The goals of training are for learners to demonstrate long-term
      retention of knowledge and skills gained and to be able to transfer this learning
      from the context of training into different situations and contexts, such as
      those encountered in the workplace. Thus, to conclude that learning has taken
      place, it is essential to study performance after learners have acquired
      knowledge and skills to see how well those have been retained and generalised.
      The current study builds on previous work conducted by the authors that described
      and evaluated an intervention designed to improve information management
      knowledge, skills and use of Web-based resources by participants from generalist
      primary care practices. This cross-over study found that both groups of
      participants--those who received training initially and those who received
      training later--showed the same improvements when assessed 15 months and three
      months, respectively, after training. Given the definition of learning as
      'relatively permanent', we wondered if these improvements would last.
      Participants in the original three phases of the study completed questionnaires
      during each phase; for the current study they were asked to complete a fourth
      questionnaire administered 27 and 15 months, respectively, after their original
      training. All variables showed non-significant differences between participants'
      scores at the end of the original study, where learning was assessed as having
      occurred, and the current administration of the questionnaire. Demonstrated long
      term retention of knowledge and skills and generalisation to the workplace show
      that the goals of training have been met.

PMID- 19094409
TI  - Do electronic medical record (EMR) demonstrations change attitudes, knowledge,
      skills or needs?
AB  - INTRODUCTION: Electronic medical records (EMRs) are the future of primary care.
      Transition to electronic records can have a significant impact on physicians,
      office staff, nursing staff and patients. There are no published EMR studies
      combining these four populations or studies that have evaluated the impact of EMR
      demonstrations. To better understand the impact of EMRs, an online survey was
      administered before and after EMR demonstrations. METHODS: A longitudinal cohort
      survey design was used to assess primary outcomes (attitudes, knowledge, skills
      and needs) related to EMRs in four populations that were divided into two groups-
      one of physicians and the other of nursing staff, office staff and patients. A
      total of 39 participants (19 physicians and 20 staff/patients) completed a
      pretest survey four weeks prior to and post-test surveys at four and ten weeks
      after EMR demonstrations. Mean composite scores for each primary outcome were
      calculated for each group and mean differences were calculated and compared
      within and between groups--from baseline to four weeks and four to ten weeks
      using paired t-tests and Student's t-tests, respectively. RESULTS: Groups
      differed in several areas: physicians were younger, had more education and had
      fewer years of experience in a primary care office. There were no significant
      differences in gender or computer experience between groups. Staff/patients
      reported significant improvements in attitudes, knowledge and needs from baseline
      to four weeks (P<0.05, P<0.01 and P<0.05). Physician attitudes, knowledge and
      needs significantly increased at week four (P<0.05, P<0.01 and P<0.05).
      Attitudes, knowledge and needs were sustained in both groups from week four
      through to week ten. CONCLUSION: EMR demonstrations improved attitudes, knowledge
      and needs of staff/patients and physicians. EMR demonstrations may be effective
      in favorably influencing healthcare personnel towards EMRs.

PMID- 19094410
TI  - The use of information technology to enhance diabetes management in primary care:
      a literature review.
AB  - BACKGROUND: Evidence suggests that a more structured approach to diabetes care
      can lead to better health outcomes. We needed to develop an evidence-based
      conceptual framework for the Chronic Disease Management Network (CDM-Net) project
      which aims to use information technology (IT) to optimally support diabetes care
      in the Barwon region of Victoria, Australia. OBJECTIVE: This review aims to
      demonstrate the benefits of IT in supporting a systematic approach to diabetes
      management in general practice and to increase our understanding of perceived
      barriers to and facilitators to the use of IT in this context. METHODS: The
      literature review was based on articles extracted from relevant databases by
      using search terms related to type 2 diabetes and IT. Eligible papers were those
      based on original studies which evaluated some form of IT intervention in medical
      practice and were published after 1996 in the English language. Studies
      evaluating the use of telemedicine were excluded. FINDINGS: IT has been used to
      provide support to patients, enhance changes in healthcare delivery and provide
      clinicians with access to expertise and timely, useful data about individual
      patients and populations. IT use has been associated with a corresponding
      improvement in measures of diabetes care including HbA1c, blood pressure and
      lipids, and in the frequency of eye and foot exams. Important barriers to using
      IT in diabetes care include confidentiality concerns, inadequate funding,
      workforce shortages, lack of time and anxiety about change. Adequate training and
      integration into the usual process of care are essential facilitators to
      implementing IT. CONCLUSIONS: IT can be used to improve diabetes care by
      promoting a productive and informative interaction between the patient and the
      care team.

PMID- 19094411
TI  - The exceptional potential for quality improvement methods in the design and
      modelling of complex interventions.

PMID- 19094412
TI  - Organisational interventions in primary care.

PMID- 19094414
TI  - Quality in Primary Care indexed in Medline in 2008.

PMID- 19094413
TI  - Educational interventions for improving primary care.

PMID- 19094415
TI  - Change capacity: the route to service improvement in primary care.
AB  - BACKGROUND: This paper draws on data from five English primary care trust (PCT)
      case studies which formed part of a larger research project that explored the
      roles and relationships of clinical managers and their colleagues in periods of
      change within different healthcare organisations. AIMS: This article uses
      empirical data to further our understanding of how primary care organisations can
      successfully implement service improvements. METHOD: Qualitative methods were
      used to compare across multiple cases. Three methods were utilised comprising
      semi-structured interviews, document analysis and observation at meetings.
      Through an iterative process of data coding using the NVivo data analysis
      software, final conclusions developed and became more explicit. Data were
      collected between mid-2002 and 2005. RESULTS: Our analysis demonstrates the
      important influence of context on the change process. The case studies provide
      evidence of the nature of the relationships between context and progress in
      organisational change. We identified three interrelated dimensions of
      organisational context that played a crucial role in the progress or otherwise of
      service improvement. CONCLUSION: We conclude that primary care organisations need
      to have three key features in combination to successfully implement service
      improvements. These are (i) the presence of change leaders, at several levels
      throughout the organisation; (ii) a coherent change strategy; and (iii) a sound
      foundation of relationships between managers and clinical professional groups.

PMID- 19094416
TI  - Older people with complex long-term health conditions. Their views on the
      community matron service: a qualitative study.
AB  - BACKGROUND: The Department of Health in the UK has suggested that older people
      with complex health problems may benefit from a case-management approach to meet
      their needs. The NHS has since invested heavily in community matrons as one
      method of tackling managed care. Matrons are highly trained nurses, able to
      diagnose, prescribe and manage patients with long-term conditions within primary
      care. Early evidence suggests that the matron approach does not achieve the
      government targets of reducing unplanned hospital admissions. AIM: To explore the
      experiences and attitudes of older people who have a community matron so that we
      may gain an understanding of the successes and failures of this form of case
      management. DESIGN OF STUDY: Qualitative study using one-to-one interviews with
      patients and carers. Setting Nottingham and surrounding rural areas during 2006
      2007. METHOD: A purposive sample of patients recruited from community matron
      caseloads. In-depth semi-structured interviews were audiotaped and transcribed.
      Analysis for emergent themes used a template approach and was validated by
      discussion with lay advisors and community matrons and by separate analysis of a
      sample of interviews by an independent researcher. RESULTS: Twenty-four
      participants were recruited. They often valued their matron as a personal friend
      as well as a professional. Many suggested that matrons improved their global
      health, reduced the workload of general practitioners, kept them out of
      residential care, reduced the need for social and psychological care, and
      supported their carers. Some were unclear why they had been selected for the
      matron service and knew of others they felt would benefit more than them.
      CONCLUSIONS: Matrons seem to be generally highly valued on a professional and
      personal level, almost filling the role of family doctor vacated by changing
      practices in modern primary care. Participants suggested several reasons why
      matrons could be economically justified, which need further investigation. The
      methods of case selection for these services also need to be questioned.

PMID- 19094417
TI  - Quality improvement in primary care mental health practice. A case for political
      intervention?
AB  - Improving the quality and consistency of detecting and providing for so-called
      common mental health problems in primary care settings is a contemporary issue.
      Such conditions are common and they are now recognised as a significant burden
      upon the economy. Though energetically pursued for much of the last half century,
      a medical approach based upon syndromal diagnosis and treatment has not provided
      a clear, evidence-based approach to their management that can form the basis of
      an educational intervention. Where that has been attempted and evaluated, it has
      been found wanting. A more politically driven imperative has stimulated 'top
      down' and firmly managed processes of change, encouraged by fresh investment.
      Improving Access to Psychological Therapies will not be the first programme to
      influence mental health services in this way. Experience of other programmes of
      deliberately managed change suggests that this approach can be effective and
      productive, particularly in a context which mental health exemplifies, where
      there are relatively few clinical certainties and a multitude of opinions.

PMID- 19094418
TI  - Combined horizontal and vertical integration of care: a goal of practice-based
      commissioning.
AB  - Practice-based commissioning (PBC) in the UK is intended to improve both the
      vertical and horizontal integration of health care, in order to avoid escalating
      costs and enhance population health. Vertical integration involves patient
      pathways to treat named medical conditions that transcend organisational
      boundaries and connect community-based generalists with largely hospital-sited
      specialists, whereas horizontal integration involves peer-based and cross
      sectoral collaboration to improve overall health. Effective mechanisms are now
      needed to permit ongoing dialogue between the vertical and horizontal dimensions
      to ensure that medical and nonmedical care are both used to their best advantage.
      This paper proposes three different models for combining vertical and horizontal
      integration - each is a hybrid of internationally recognised ideal types of
      primary care organisation. Leaders of PBC should consider a range of models and
      apply them in ways that are relevant to the local context. General practitioners,
      policy makers and others whose job it is to facilitate horizontal and vertical
      integration must learn to lead such combined approaches to integration if the UK
      is to avoid the mistakes of the USA in over-medicalising health issues.

PMID- 19094419
TI  - Ethical considerations in relation to aspirin prophylaxis.
AB  - Low-dose aspirin prophylaxis, 75-150 mg per day, reduces the risk of vascular
      events and there is also promising evidence that it may also reduce the risk of
      cancer. Increased use of aspirin may confer considerable benefits to the
      population, but the risk of causing a gastric bleed is certainly a major concern.
      There are ethical considerations related to the potential increased use of
      aspirin in the population. These include the balance of benefit and risk of the
      medicine, possible undesirable effects such as 'risk compensation' and
      'iatrogenesis', as well as a potential impact on health inequalities. More
      research is therefore needed on aspirin, particularly to define and describe the
      population use of the drug. More evidence on aspirin, including an ongoing
      randomised controlled trial on vascular events, will allow appropriate policy
      responses to be made.

PMID- 19094420
TI  - Learning how to make things happen: a report of an educational intervention
      designed to support clinical governance leads in primary care.
AB  - Making Things Happen (MaTH) was devised as a six-module educational programme to
      support clinical governance leads (CGLs) in primary health care. The aim of the
      programme was to help develop practice CGLs' awareness, understanding and ability
      to initiate and manage change. The objectives of the training programme were: *
      to promote an increased and sophisticated understanding of clinical governance by
      building on knowledge gained already * to develop skills in delivering and
      sustaining improvements * to improve personal effectiveness in bringing about
      change. A pilot training programme was planned and delivered twice in 2003/2004
      to two separate cohorts of clinical governance leads (n = 30 and n = 15) from two
      pilot primary care trusts (PCTs). The six training modules were delivered to the
      two groups by the same staff but at different times and in two separate
      locations. The effectiveness of the programme was evaluated in both PCTs at three
      levels. First the content of the programme was evaluated by the CGLs that
      attended the programme. Secondly, the value of the programme to the PCT was
      considered by the PCT co-ordinators. Thirdly, the effectiveness of the programme
      was considered by the presenting team. All three groups felt that the objectives
      were met, that the principles of MaTH training were sound and that it would be a
      valuable resource to offer nationally. It was also noted that training for PCT
      local co-ordinators in how to support clinical governance would be a useful
      training co-opportunity.

PMID- 19094421
TI  - Influencing organisational change in the NHS: lessons learned from workplace
      wellness initiatives in practice.
AB  - This article presents a discussion of the key issues in influencing
      organisational change in NHS settings, in the development of workplace wellness
      interventions to improve employee health and wellbeing. To tackle poor public
      health and associated rising healthcare costs, there must be a focus on the root
      cause of many preventable diseases - unhealthy lifestyle choices. Workplace
      wellness initiatives are now an important prevention strategy adopted by socially
      responsible organisations to target the health and wellbeing of working age
      adults. Lessons learned from initiatives in secondary care suggest that effective
      implementation requires change in organisational 'health culture', through a
      combination of education, behaviour change intervention, needs-based facilities,
      and services and strategies for developing supportive and health-promoting work
      environments. Most of all, employers must demonstrate a commitment to health and
      wellness that is fully integrated with their mission, values and long-term
      vision, paving the way for sustainable lifestyle changes. Evaluation systems must
      be in place to measure the impact and outcomes of wellness schemes.

PMID- 19094422
TI  - Web alert: quality in mental health care.

PMID- 19094423
TI  - Aggrecanase and aggrecan degradation in osteoarthritis: a review.
AB  - Aggrecanase-mediated aggrecan degradation is a significant event in early-stage
      osteoarthritis (OA). Aggrecanases belonging to the 'A Disintegrin And
      Metalloproteinase with ThromboSpondin motifs' (ADAMTS) family of proteinases play
      a significant role in aggrecan depletion in osteoarthritic cartilage. There has
      been considerable interest in the possible role of these aggrecanases, especially
      ADAMTS-4 and ADAMTS-5, as therapeutic targets in OA. This article discusses
      recent data regarding ADAMTS-4 and ADAMTS-5 in OA, with emphasis on the
      relationship between aggrecanase and aggrecan degradation as well as the role of
      aggrecanase in OA.

PMID- 19094424
TI  - Glucosamine and chondroitin for osteoarthritis.
AB  - Osteoarthritis (OA) is a common, chronic disease that most frequently affects the
      knees and is a major cause of disability in the elderly. It is characterized by
      progressive cartilage loss, accompanied by secondary changes such as osteophyte
      formation and calcium deposition. Inflammatory processes are also involved,
      leading to stiffness and pain, for which patients seek treatment. Conventional
      treatment includes analgesics or non-steroidal anti-inflammatory drugs, however
      life-style changes should also be recommended, such as weight reduction and
      specific exercises. Glucosamine and chondroitin, classed as over-the-counter
      supplements or nutraceuticals, are regularly self-administered by patients with
      OA. Both agents are produced endogenously in the human body and are essential
      components of cartilage. This review discusses the evidence that supports the use
      of these agents either alone or in combination for pain relief and as disease
      modifying agents in OA.

PMID- 19094425
TI  - Insulin gene polymorphism in women with polycystic ovary syndrome.
AB  - Insulin resistance is one of the main characteristics of polycystic ovary
      syndrome (PCOS) and is probably genetically predisposed. Possible associations of
      variable nucleotide tandem repeat (VNTR) polymorphism of the insulin gene (INS)
      with insulin resistance and PCOS in Slovene patients were investigated. A total
      of 117 PCOS patients and 108 age-matched female controls were genotyped for the
      INS VNTR polymorphism using real-time polymerase chain reaction and measurement
      of appropriate biochemical and clinical parameters. Serum fasting insulin (I(0))
      levels and the homeostasis model assessment index were significantly elevated in
      PCOS patients compared with controls. Class III INS VNTR alleles were
      significantly more frequent in the PCOS group. The interaction between body mass
      index and INS VNTR genotype was a significant predictor of serum I(0) level. The
      interaction of obesity and the III/III INS VNTR genotype might be a risk factor
      for the development of PCOS.

PMID- 19094426
TI  - The relationship between clinico-biochemical characteristics and psychiatric
      distress in young women with polycystic ovary syndrome.
AB  - The relationship between clinico-biochemical characteristics and self reported
      psychological parameters in 42 women with polycystic ovary syndrome (PCOS) and 42
      age-matched healthy controls was examined. The General Health Questionnaire was
      used (GHQ-12) to ascertain emotional distress and the Beck Depression Inventory
      (BDI) to determine depressive symptoms. Emotional distress, depressive symptoms,
      hirsutism score, body mass index (BMI), waist-to-hip ratio (WHR), luteinizing
      hormone/follicle-stimulating hormone ratio, serum total testosterone,
      dehydroepiandrosterone sulphate levels and the insulin resistance index were
      significantly greater in women with PCOS than in healthy women. The BDI and GHQ
      12 scores of the women with PCOS were significantly higher than those of the
      control group (BDI, 11.69 +/- 9.49 vs 5.80 +/- 4.58; GHQ-12, 3.38 +/- 3.38 vs
      1.54 +/- 1.97, respectively), and BMI and WHR were positively correlated with the
      BDI and GHQ-12 scores. Clinicians should be aware of the increased risk of
      emotional distress and depression in women with PCOS, especially those who are
      obese, and of the need to screen these patients for such symptoms.

PMID- 19094427
TI  - Ovarian stimulation in obese and non-obese polycystic ovary syndrome using a low
      dose step-up regimen with two different starting doses of recombinant follicle
      stimulating hormone.
AB  - Sixty-seven infertile women with polycystic ovary syndrome (PCOS) were divided
      into two groups, obese and non-obese, according to their body mass index. Waist
      to-hip ratio, insulin resistance, total testosterone and dehydroepiandrosterone
      sulphate levels were significantly elevated in obese, compared with non-obese,
      patients. Both groups were treated with a low-dose step-up protocol of
      recombinant follicle-stimulating hormone (rFSH) with a starting dose of 50 IU/day
      and, every third day, a 25-IU increase in the dose until the appropriate dose was
      achieved for each individual, up to a maximum of 175 IU/day. In the obese group
      only, repeat therapy commenced in the second ovulatory cycle in women who had not
      become pregnant, however a starting dose of 75 IU/day was then used, with
      incremental and maximum dose as before. The results of the starting dose of 75
      IU/day rFSH were compared with the results of a 50 IU/day rFSH starting dose in
      the obese group. A starting dose of 50 IU/day rFSH in a low-dose step-up regimen
      was found to be effective, safe and well-tolerated for inducing follicular
      development in non-obese infertile women with PCOS. However, for obese PCOS
      patients, a starting dose of 75 IU/day rFSH is recommended.

PMID- 19094428
TI  - Transvaginal ultrasonography and saline infusion sonohysterography for the
      detection of intra-uterine lesions in pre- and post-menopausal women with
      abnormal uterine bleeding.
AB  - This prospective study investigated 79 pre- and 25 post-menopausal women with
      abnormal uterine bleeding who underwent conventional transvaginal ultrasonography
      (TVS) and saline infusion sonohysterography (SIS) and compared the results with
      histopathological findings obtained by dilatation and curettage, hysteroscopy or
      hysterectomy. Histological examination revealed normal endometrial histology in
      28 patients, intracavitary polyps in 46 patients, submucosal fibroids in 18
      patients, intramural fibroids in six patients and endometrial hyperplasia in six
      patients. The sensitivity and specificity of TVS in detecting endometrial polyps
      were 65.2% and 87.9%, respectively, compared with 91.3% and 93.1% for SIS. The
      sensitivity and specificity of TVS in detecting uterine fibroids were 95.8% and
      95.0%, respectively, versus 91.6% and 98.7% for SIS. These results show that SIS
      is a satisfactory method of identifying lesions and that it is easy and cost
      effective, and improves on the diagnostic utility of TVS. SIS is also a less
      invasive alternative to hysteroscopy, so should result in less morbidity in the
      evaluation of abnormal uterine bleeding in women.

PMID- 19094429
TI  - Detecting anti-FcepsilonRI autoantibodies in patients with asthma by flow
      cytometry.
AB  - Autoimmune diseases have been implicated in the development of intrinsic asthma,
      however little data are available on the role of autoimmunity in the pathogenesis
      of asthma. The purpose of this study was to investigate circulating
      autoantibodies against the high-affinity receptor for immunoglobulin E,
      FcepsilonRI, in patients with asthma. Seventy-eight patients with asthma and 32
      healthy control subjects were included. All individuals were tested using a
      triple-staining flow cytometry-based basophil activation test (BAT) for the
      potential presence of autoantibodies against FcepsilonRI. Of the 78 asthma
      patients, 29 (37.2%) had a positive BAT result, indicating that their serum was
      able to activate basophils, compared with only four (12.5%) of the control group,
      a statistically significant between-group difference. These data suggest that
      some asthma patients have aberrant anti-FcepsilonRI autoantibodies, which implies
      that autoimmunity may be one factor involved in the pathogenesis of intrinsic
      asthma.

PMID- 19094430
TI  - Effect of thiamine pyrophosphate on levels of serum lactate, maximum oxygen
      consumption and heart rate in athletes performing aerobic activity.
AB  - The aim of this study was to determine the effect of thiamine pyrophosphate (TPP)
      on serum lactate levels, maximum oxygen consumption (Vo(2max)) and heart rate in
      male athletes performing aerobic activity. A double-blind, randomized, crossover
      study was performed in which lactate levels, Vo(2max) and heart rates in 27 male
      athletes were compared at rest and after exercise, following administration of
      placebo (sodium chloride 0.9%) or TPP (1 mg/kg). At rest, serum lactate levels
      after placebo or TPP were similar; however, after exercise, the levels were lower
      in the athletes after taking TPP than after placebo. During exercise, Vo(2max) in
      athletes on TPP was higher than on placebo. At rest, heart rate after taking
      placebo or TPP was similar but, after exercise, heart rate was lower after taking
      TPP than after placebo. It is concluded that TPP caused serum lactate levels and
      heart rate to be lower than placebo and Vo(2max) to be higher in athletes
      performing aerobic physical activity.

PMID- 19094431
TI  - Expression of ubiquitin in peripheral inflammatory cells from patients with
      coronary artery disease.
AB  - In addition to its role in the removal of damaged and unneeded proteins, the
      ubiquitin-proteasome system (UPS) may play a key role in coronary artery disease
      (CAD). To investigate the expression of ubiquitin in monocytes and lymphocytes
      isolated from patients at different stages of CAD, 120 patients with CAD (40 with
      acute myocardial infarction [AMI], 40 with unstable angina pectoris [UAP] and 40
      with stable angina pectoris [SAP]) were selected; 40 patients with normal
      coronary arteries served as controls. At both the mRNA and protein levels,
      ubiquitin expression was higher in patients with CAD than in controls, and
      patients with AMI had a much higher expression of ubiquitin (at both the mRNA and
      protein levels) than those with SAP and UAP. These data indicate that ubiquitin
      expression increased with increasing severity of CAD, suggesting that ubiquitin
      may play a critical role in the development and progression of CAD.

PMID- 19094432
TI  - Effects of remifentanil and fentanyl on the cell-mediated immune response in
      patients undergoing elective coronary artery bypass graft surgery.
AB  - This prospective randomized pilot study compared the influence of fentanyl-based
      versus remifentanil-based anaesthesia on cytokine responses and expression of the
      suppressor of cytokine signalling (SOCS)-3 gene following coronary artery bypass
      graft surgery. Forty patients were assigned to receive anaesthesia with either
      intravenous remifentanil (0.3 - 0.6 microg/kg per min; n = 20) or intravenous
      fentanyl (5 - 10 microg/kg per h; n = 20). Levels of interleukin (IL)-6, IL-10,
      tumour necrosis factor-alpha and interferon-gamma (IFN-gamma) and the expression
      of SOCS-3 were measured pre- and post-operatively. The data from 33 of the
      patients were analysed. The IFN-gamma/IL-10 ratio after concanavalin A
      stimulation in whole blood cells on post-operative day 1 and SOCS-3 gene
      expression on post-operative day 2 were significantly lower in the remifentanil
      group than in the fentanyl group. The time in the intensive care unit was also
      significantly lower in the remifentanil group. These findings suggest that
      remifentanil can attenuate the exaggerated inflammatory response that occurs
      after cardiac surgery with cardiopulmonary bypass. Further clinical trials are
      required to define the influence of choice of intra-operative opioid on post
      operative outcome.

PMID- 19094433
TI  - Pre-operative atorvastatin therapy to decrease the systemic inflammatory response
      after coronary artery bypass grafting.
AB  - The effect of pre-operative atorvastatin on systemic inflammatory response
      syndrome (SIRS), often seen after coronary artery bypass grafting (CABG) was
      evaluated in 40 patients undergoing elective CABG. Patients were divided into two
      groups: group I (pre-operative LDL cholesterol > or = 100 mg/dl; n = 20) received
      20 mg/day atorvastatin for at least 15 days pre-operatively; group II (pre
      operative LDL cholesterol < 100 mg/dl; n = 20) did not receive
      antihyperlipidaemic agents. All patients underwent CABG with cardiopulmonary
      bypass. Blood samples were taken pre-operatively and 24 h post-operatively. There
      were no significant differences between the two groups in terms of demographic,
      pre-operative or operative parameters. At 24 h post-operatively, median high
      sensitivity C-reactive protein and mean interleukin-6 levels were significantly
      lower in group I compared with group II. There were no other significant
      differences in post-operative parameters between the two groups, except for
      duration of stay in the intensive care unit, which was shorter in group I
      patients. In conclusion, pre-operative atorvastatin treatment in patients
      undergoing elective CABG decreased inflammation parameters and could be effective
      in preventing SIRS.

PMID- 19094434
TI  - Decline in pneumonia and acute otitis media after the introduction of childhood
      pneumococcal vaccination in Liguria, Italy.
AB  - The effect of the pneumococcal conjugate vaccine immunization programme on
      pneumococcal-associated or potentially pneumococcal-associated hospital
      admissions in the Italian region of Liguria was assessed. Hospital admission
      rates were compared in subjects belonging to birth cohorts before and after the
      introduction of widespread immunization for 0 - 2-year old children with a seven
      valent conjugate vaccine (PCV7). Significant reductions in hospitalization rates
      for all-cause and pneumococcal pneumonia and for acute otitis media were observed
      in subjects born after widespread uptake of the vaccine. The preventive fraction
      (a measure of vaccine effectiveness) ranged from 15.2% for all cause pneumonia to
      70.5% for pneumococcal pneumonia. This study contributes to the growing body of
      information that supports the beneficial effect of PCV7 vaccination.

PMID- 19094435
TI  - Distribution, optimum detection time and antimicrobial susceptibility rates of
      the microorganisms isolated from blood cultures over a 4-year time period in a
      Turkish university hospital and a review of the international literature.
AB  - This study retrospectively examined 8986 blood cultures from patients over a 4
      year time period in an eastern Turkish university hospital to determine the
      detection times and distribution of isolated microorganisms using the automated
      BACTEC 9050 and BACTEC 9120 systems. A total of 1914 (21.3%) blood cultures
      contained pathogenic microorganisms and 252 (2.8%) positive cultures were
      considered contaminated. Of all the cultures, 18 (0.2%) were false positives and
      224 (2.5%) were false negatives. In cultures containing pathogenic
      microorganisms, Gram-positive and Gram-negative bacterial isolation rates were
      436 (22.8%) and 1440 (75.2%), respectively, and yeasts (all Candida sp.) were
      found in 38 (2.0%) cultures. Coagulase-negative staphylococci occurred in 936
      (48.9%) cultures and Staphylococcus aureus occurred in 302 (15.8%) cultures. The
      mean detection time for all of the pathogens was 21 h and Brucella spp were
      isolated within 10 days. This study helps in understanding the epidemiology of
      the region and in providing positive therapeutic approaches. A review of the
      international literature helps to place this understanding into a global context.

PMID- 19094436
TI  - Advanced malignant pleural or peritoneal effusion in patients treated with
      recombinant adenovirus p53 injection plus cisplatin.
AB  - The aim of this study was to evaluate the efficacy of recombinant adenovirus p53
      agent (rAd-p53) injection combined with cisplatin (CDDP) for the treatment of
      malignant pleural or peritoneal effusion. After puncture drainage, patients in
      the treatment group (n = 27) received intracavitary administration of rAd-p53 (2
      x 10(12) virus particles) once a week for 4 weeks. At 48 h after each rAd-p53
      injection, patients were given intracavitary administration of cisplatin 60
      mg/m(2). This administration procedure continued once a week for 4 weeks. The
      control group (n = 21) received the same intracavitary therapy as the treatment
      group but without rAd-p53 therapy. Efficacy was evaluated by clinical
      observations, computed tomography, tumour markers, Karnofsky score and short-term
      follow-up. The total effective rates for the treatment group (63.0%) were
      significantly higher than for the control group (42.9%), suggesting that the
      treatment group benefited over the control group. In conclusion, rAd-p53 therapy
      is a safe and effective treatment for advanced malignant pleural or peritoneal
      effusion.

PMID- 19094437
TI  - Assessment of self-reported and health-related quality of life in patients with
      brain tumours using a modified questionnaire.
AB  - Assessment of quality of life (QoL) in patients who undergo surgery for brain
      tumours helps to guide surgery, reduce recurrence and minimize morbidity. This
      study validated a 25-item, modified QoL questionnaire based on the Medical
      Outcomes Survey SF-36 and the Karnofsky Performance Scale. The aims were for it
      to be brain tumour specific for Chinese patients, hence more sensitive, more
      acceptable, briefer and more easily used. A total of 431 patients with brain
      tumours were compared with 96 age-matched healthy controls. A surgery-related QoL
      curve was used to help identify a threshold satisfaction point for QoL.
      Physiological function, psychological function, satisfaction with medical care
      and self-care ability of the patients were compared pre-operatively and post
      operatively. Cronbach's alpha-coefficient was 0.9521 and the correlation
      coefficient was 0.8685, suggesting good reliability and repeatability. With the
      exception of psychological function, which deteriorated, the modified QoL showed
      significant improvement in physiological function, satisfaction with medical care
      and self-care ability, and serves to stress the importance of post-operative
      psychological support.

PMID- 19094438
TI  - The combination of low-dose levobupivacaine and fentanyl for spinal anaesthesia
      in ambulatory inguinal herniorrhaphy.
AB  - This study investigated whether the addition of 25 microg intrathecal fentanyl to
      levobupivacaine spinal anaesthesia for outpatient inguinal herniorrhaphy allows a
      sub-anaesthetic levobupivacaine dose to be used. Forty patients were assigned to
      receive 5 mg levobupivacaine 0.5% mixed with 25 microg fentanyl (group LF) or 7.5
      mg levobupivacaine 0.5% (group L). The highest sensory block levels achieved were
      T7 (range T5 - T9) and T6 (range T4 - T9) in groups LF and L, respectively. The
      times to two-segment regression, S2 regression, ambulation, urination and
      discharge were all significantly shorter in group LF than group L. These results
      indicate that, for outpatient inguinal herniorrhaphy, intrathecal fentanyl
      combined with low-dose levobupivacaine provides good quality spinal anaesthesia
      and minimizes the need for intra-operative analgesia. This protocol is well
      suited for the outpatient setting because it features rapid recovery of full
      motor power, sensory function and bladder function.

PMID- 19094439
TI  - Randomized, multicentre, comparative clinical evaluation of cefuroxime-sulbactam
      versus amoxicillin-clavulanic acid therapy in the treatment of lower respiratory
      tract infections.
AB  - This randomized, multicentre, comparative study evaluated the efficacy and safety
      of treatment with cefuroxime-sulbactam compared with amoxicillin-clavulanic acid
      (co-amoxiclav) in patients with lower respiratory tract infections (LRTIs). The
      study enrolled 75 adult in-patients with moderate to severe LRTIs. Patients were
      treated intravenously for 7 - 10 days. The treatment groups were comparable at
      baseline with respect to demographic and disease characteristics. Efficacy was
      evaluated in 72 patients. The clinical success rate was statistically superior in
      patients treated with cefuroxime-sulbactam (100%) compared with patients treated
      with amoxicillin-clavulanic acid (88%). The bacteriological success rate was 95%
      and 100% for cefuroxime-sulbactam and amoxicillin-clavulanic acid, respectively,
      with no significant difference between treatments. Both treatments were safe and
      well tolerated. One patient in the cefuroxime-sulbactam group reported
      convulsions, which the investigator considered were probably not related to the
      study medication. Cefuroxime-sulbactam can be an effective alternative empirical
      treatment for LRTIs.

PMID- 19094440
TI  - Imaging the effects of propofol on human cerebral glucose metabolism using
      positron emission tomography.
AB  - The effects of propofol on glucose metabolism in different cerebral regions were
      observed, using positron emission tomography (PET) technology, to determine a
      possible cerebral target region. Seven healthy volunteers were injected with
      (18)F-fluorodeoxyglucose developing agent for PET scanning whilst awake (control
      group T1), during sedation (induced by 1.5 microg/ml propofol administered by
      target controlled injection [TCI], group T2) and when unconsciousness (induced by
      2.5 microg/ml propofol administered by TCI, group T3). Whole brain glucose
      metabolism was reduced during propofol anaesthesia; this was initially observed
      in the cortical areas at the lower dose of propofol (group T2) but extended to
      the subcortical regions, especially the thalamus and hippocampus, at the higher
      dose (group T3). This suggests that these regions of the brain might be important
      targets that are susceptible to propofol.

PMID- 19094441
TI  - Assessment of the efficacy of bio-absorbable oxidized regenerated cellulose for
      prevention of post-operative pericardial adhesion in the rabbit model.
AB  - Pericardial adhesions complicate re-operative cardiac surgery and several
      attempts have been made to reduce adhesion formation. The efficacy of bio
      absorbable oxidized regenerated cellulose in preventing post-operative
      pericardial adhesions was evaluated in the present study. Forty New Zealand white
      rabbits were divided into four groups of 10. In all rabbits an area of
      pericardium (2 x 2 cm) was excised. The wound was left open in groups 1 and 2 but
      replaced with bio-absorbable oxidized regenerated cellulose in groups 3 and 4.
      Rabbits in groups 1 and 3 were killed 3 weeks after surgery and those in groups 2
      and 4 were killed at 6 weeks. Groups 1 and 2 showed more severe pericardial
      adhesions, more fibrous reaction and increased visibility of coronary vessels
      than groups 3 and 4, although there was no difference in inflammation. Light
      microscopy showed a mesothelium-like cell layer in groups 3 and 4. It is
      concluded that bio-absorbable oxidized regenerated cellulose may be suitable in
      patients receiving staged cardiac surgery and in those with a high probability of
      re-operation.

PMID- 19094442
TI  - Scavenger receptor class B type I mediates cell entry of hepatitis C virus.
AB  - This study assessed the functional role of human scavenger receptor class B type
      I (SR-BI) as a putative hepatitis C virus (HCV) receptor using Chinese hamster
      ovary (CHO) cells transfected with human SR-BI (CHO-huSR-BI). The expression of
      SR-BI by primary Tupaia hepatocytes (PTHs), human hepatocarcinoma cell line
      (HepG2) cells, untransfected CHO cells and CHO-huSR-BI cells was analysed by
      Western blotting. Receptor competition assays showed that anti-SR-BI antibodies
      that block the binding of soluble envelope glycoprotein E2 could prevent HCV
      infection. Pre-incubation of CHO-huSR-BI and HepG2 cells with anti-SR-BI
      antibodies resulted in marked inhibition of E2 binding. After incubation with HCV
      RNA-positive serum from a patient with chronic HCV infection, however, HCV
      infection could not be detected in CHO-huSR-BI cells, but was detected in PTHs.
      These results demonstrate that, whilst SR-BI represents an important cell surface
      molecule for HCV infection, the presence of SR-BI alone is insufficient for HCV
      entry.

PMID- 19094443
TI  - Effects of Origanum onites on endothelial function and serum biochemical markers
      in hyperlipidaemic patients.
AB  - The effects of Origanum onites on endothelial function and antioxidative status
      were investigated in 48 patients with mild hyperlipidaemia who required no drug
      therapy. All participants were given lifestyle and low-fat dietary advice,
      however 32 of the patients (study group) were also prescribed 25 ml of aqueous
      distillate of Origanum onites to be taken after each meal for 3 months. The
      remaining 16 patients were the control group. Various biochemical markers and
      endothelial function parameters were measured at baseline and after 3 months. A
      significantly greater increase in high density lipoprotein-cholesterol and
      significantly greater decreases in low density lipoprotein-cholesterol,
      apolipoprotein B, lipoprotein(a) and high sensitivity C-reactive protein occurred
      in the study group compared with the control group over the 3-month study period.
      Paraoxonase and arylesterase activities, and flow- and nitroglycerine-mediated
      dilatation of the brachial artery showed significantly greater increases in the
      study group compared with the changes in the control group. In conclusion,
      consumption of Origanum onites distillate had beneficial effects on lipid
      profiles, antioxidant status and endothelial function in patients with mild
      hyperlipidaemia.

PMID- 19094444
TI  - Catalase activity, serum trace element and heavy metal concentrations, and
      vitamin A, D and E levels in pre-eclampsia.
AB  - Catalase (antioxidant enzyme) activity in erythrocytes and serum levels of trace
      elements (copper, iron, zinc), heavy metals (cadmium, cobalt) and vitamins A
      (retinol), D (cholecalciferol) and E (alpha-tocopherol) were measured in 145
      subjects comprising 47 pre-eclamptic pregnant women (PE), 48 healthy pregnant
      women (HP) and 50 healthy non-pregnant controls (NP). Catalase, vitamins A, D and
      E and levels of cobalt were significantly lower in the PE group compared with the
      HP and NP groups, whereas levels of copper, iron and cadmium were significantly
      higher in the PE group than in the HP and NP groups. Levels of zinc were
      significantly lower in both the PE and HP groups compared with the NP group. This
      assessment of oxidant/antioxidant imbalance in pregnant women could be useful in
      the early identification of pre-eclampsia and antioxidant supplementation in the
      early weeks of gestation might be useful.

PMID- 19094445
TI  - Anti-tumour effects of exosomes in combination with cyclophosphamide and
      polyinosinic-polycytidylic acid.
AB  - We examined the anti-tumour activity of exosomes derived from dendritic cells
      (DCs) in combination with cyclophosphamide (CTX) and polyinosinic-polycytidylic
      acid sodium salt (poly I:C). DCs were pulsed with L1210 lymphocytic leukaemia
      cell antigen and lipopolysaccharide. The exosomes that the DCs secreted were
      purified. In vitro, the anti-tumour activity of exosomes was assessed by
      measuring their ability to induce spleen cell proliferation and the extent to
      which they induced spleen cells to kill L1210 cells. Poly I:C was able to induce
      DC maturation. DC-derived exosomes stimulated spleen cell proliferation and
      enhanced the cytotoxic effects of spleen cells in vitro. DC-derived exosomes, in
      combination with CTX and poly I:C, suppressed L1210 tumour growth in vivo and
      gave the greatest prolongation of survival time in tumour-bearing DBA2 mice.
      These findings suggest that this combination of a tumour vaccine, a conventional
      anti-cancer agent and a promoter of DC maturation might be a useful anti-cancer
      therapy.

PMID- 19094446
TI  - Effects of polymorphism of the beta(1) adrenoreceptor and CYP2D6 on the
      therapeutic effects of metoprolol.
AB  - Metoprolol is a lipophilic beta(1) selective adrenergic receptor antagonist used
      in antihypertensive therapy. It is metabolized by the protein product of the
      cytochrome P450 2D6 (CYP2D6) gene. Few studies have been performed on the
      association between the beta(1) adrenoreceptor, CYP2D6 polymorphism and blood
      pressure. The one reported here is a prospective, observational, clinical study
      in Chinese Han hypertensive patients on the combined influences of CYP2D6 and
      beta(1) adrenoreceptor polymorphisms on the therapeutic effects of metoprolol in
      300 out-patients with essential hypertension. The same dose of metoprolol
      achieved different therapeutic effects in patients with different CYP2D6 and
      beta(1) adrenoreceptor polymorphisms. Additionally, different doses of metoprolol
      could achieve the same therapeutic effects in patients with different CYP2D6 and
      beta(1) adrenoreceptor polymorphisms. Knowledge of the combination of CYP2D6 and
      beta(1) adrenoreceptor polymorphisms may be used to guide antihypertensive
      therapy using beta(1) adrenoreceptor antagonists.

PMID- 19094447
TI  - Infrared thermography based on artificial intelligence for carpal tunnel syndrome
      diagnosis.
AB  - Thermography for the measurement of surface temperatures is well known in
      industry, although is not established in medicine despite its safety, lack of
      pain and invasiveness, easy reproducibility, and low running costs. Promising
      results have been achieved in nerve entrapment syndromes, although thermography
      has never represented a real alternative to electromyography. Here an attempt is
      described to improve the diagnosis of carpal tunnel syndrome with thermography
      using a computer-based system employing artificial neural networks to analyse the
      images. Method reliability was tested on 112 images (depicting the dorsal and
      palmar sides of 26 healthy and 30 pathological hands), with the hand divided into
      12 segments and compared relative to a reference. Palmar segments appeared to
      have no beneficial influence on classification outcome, whereas dorsal segments
      gave improved outcome with classification success rates near to or over 80%, and
      finger segments influenced by the median nerve appeared to be of greatest
      importance. These are preliminary results from a limited number of images and
      further research will be undertaken as our image database grows.

PMID- 19094448
TI  - Plasma ghrelin levels and weight loss in Chinese Uygur patients with chronic
      obstructive pulmonary disease.
AB  - Ghrelin is an important orexigenic hormone that reduces fat oxidation and
      increases adiposity. This study investigated plasma ghrelin levels in Chinese
      Uygur patients with chronic obstructive pulmonary disease (COPD). Plasma ghrelin
      and anabolic and catabolic factors were measured in 38 patients and 24 control
      subjects. COPD patients were divided into two groups based on body mass index
      (BMI): underweight (BMI < 20 kg/m(2), n = 18) or normoweight (BMI > or = 20
      kg/m(2), n = 20). Plasma ghrelin levels were found to be significantly higher in
      underweight than in normoweight patients or healthy controls. Circulating tumour
      necrosis factor-alpha and interleukin-6 concentrations were significantly higher
      in underweight than in normoweight patients, whereas insulin concentrations were
      significantly lower. Plasma ghrelin levels correlated negatively with forced
      expiratory volume in 1 s (FEV(1); r = 0.35), but did not significantly correlate
      with FEV(1)/forced vital capacity. Plasma ghrelin levels were elevated in
      underweight COPD patients and were associated with cachexia and abnormal
      pulmonary function.

PMID- 19094449
TI  - Detection of coagulase activity in pathogenic Candida species.
AB  - The coagulase activities of various Candida spp were assessed using a classical
      tube test. A total of 125 clinical Candida isolates representing eight species
      (C. albicans, C. parapsilosis, C. tropicalis, C. glabrata, C. kefyr, Geotrichum
      candidum, C. krusei and C. guilliermondii) were incubated with rabbit, sheep or
      human plasma. After 24 h incubation, 29/64 (45.3%) C. albicans isolates and 23/61
      (37.7%) non-albicans Candida strains were positive for coagulase in rabbit
      plasma, whereas 20/64 (31.2%) C. albicans and 6/61 (9.8%) non-albicans Candida
      isolates were positive for coagulase in sheep plasma. None of the tested Candida
      isolates reacted positively in human plasma. These results suggest that rabbit
      plasma is the most appropriate medium for detection of coagulase activity in
      Candida spp. Variations in coagulase production by Candida spp may be related to
      their pathogenicity. It is concluded that the laboratory detection of coagulase
      activity in clinical isolates of Candida spp may help the diagnosis of Candida
      related infections.

PMID- 19094450
TI  - Pilot Study: effects of parenteral glutamine dipeptide supplementation on
      neutrophil functions and prevention of chemotherapy-induced side-effects in acute
      myeloid leukaemia patients.
AB  - The effect of parenteral glutamine dipeptide (Gln) supplementation on neutrophil
      phagocytosis, superoxide anion generation (SAG), prevention of chemotherapy
      induced side-effects and cost-effectiveness was examined in a pilot study of
      acute myeloid leukaemia (AML) patients receiving chemotherapy. Sixteen AML
      patients were randomized to receive intravenous supplementation with Gln (30
      g/day) or an equivalent quantity (25 g/day) of a standard amino acid mixture
      (control) on days 1 - 5 of chemotherapy. Complete blood count was evaluated twice
      a week until hospital discharge, and neutrophil phagocytosis and SAG were
      measured when absolute neutrophil count reached > 500 /microl. Patients were
      observed for development of infection, mucositis and diarrhoea. In Gln-treated
      patients, the percentage of neutrophil phagocytosis and the SAG levels were
      significantly higher than in control patients (20.5 +/- 6.0% and 18.9 +/- 2.9
      nmol/10(6) neutrophils per 10 min, respectively). The Gln-treated patients lost
      significantly less weight, tended to have shorter in-patient duration and had
      less severe oral mucositis than controls. This pilot study provides preliminary
      indication that parenteral Gln supplementation enhances neutrophil phagocytic
      function, maintains nutritional status and is cost effective. Parenteral Gln may
      also prevent oral mucositis, although further studies involving more patients
      need to be undertaken to confirm this and the other results.

PMID- 19094451
TI  - Bone turnover markers in patients with type 2 diabetes and their correlation with
      glycosylated haemoglobin levels.
AB  - The aim of this prospective, longitudinal study was to investigate, over a period
      of 12 months, the effects of metabolic control on bone turnover markers in
      patients with type 2 diabetes mellitus. The study included 17 male and 18 female
      patients with type 2 diabetes, aged 37 - 66 years. Mean follow-up period was 12
      +/- 1.2 months. Mean glycosylated haemoglobin (HbA(1C)) levels were 10.6% +/-
      1.6% at the start of the study and decreased to 7.7% +/- 1.0% by the end of the
      study. Levels of the bone resorption markers, urinary deoxypyridinoline and N
      telopeptide, were 28.6 +/- 11.6 nmol/mmol creatinine and 93.6 +/- 13.7 nmol bone
      collagen equivalents [BCE]/mmol creatinine, respectively, at the start of the
      study, and decreased significantly to 17.9 +/- 7.1 nmol/mmol creatinine and 67.8
      +/- 12.8 nmol BCE/mmol creatinine, respectively, by the end of the study. Bone
      formation parameters also significantly decreased in parallel with HbA(1c) levels
      over the study period. It is concluded that effective management of metabolic
      disorder in patients with type 2 diabetes plays an important contribution to bone
      turnover improvement.

PMID- 19094452
TI  - Amlodipine reduces predicted risk of coronary heart disease in high-risk patients
      with hypertension in Spain (The CORONARIA Study).
AB  - We evaluated the efficacy and safety of amlodipine besylate alone or in
      combination with other antihypertensive agents in high-risk hypertensive patients
      in Spanish primary care. In this 1-year, open-label, prospective cohort study,
      7468 patients were treated with amlodipine 5 - 10 mg as a monotherapy or as an
      add-on therapy to attain blood pressure control (target of < 140/90 mmHg or, in
      patients with conditions such as diabetes or chronic kidney disease, < 130/85
      mmHg). At 12 months, the primary outcome (change from baseline in predicted 10
      year coronary heart disease risk) was -8.6%, down from 24.7% at baseline
      (relative risk reduction, 31.6%). Change in blood pressure from baseline
      (162.5/95.3 mmHg) was -26.7/-14.6 mmHg, and 38.6% of patients achieved their
      blood pressure target. In summary, significant reductions in predicted coronary
      heart disease risk and blood pressure were observed with amlodipine both as a
      monotherapy and as an add-on therapy. Amlodipine was well tolerated and
      compliance with treatment was good.

PMID- 19094453
TI  - Impression of clinical worsening fails to predict interferon-beta neutralizing
      antibody status.
AB  - The development of neutralizing antibodies (NAbs) against interferon
      beta(IFNbeta) reduces clinical efficacy and markers of bioactivity in patients
      with multiple sclerosis (MS), although it has also been shown that a poor
      response to IFNbeta coincided with unexpectedly low NAb levels. To try and
      resolve this incoherency, this study investigated 2822 patients referred to a NAb
      testing facility. The reason for NAb testing was indicated for 2506 patients:
      routine testing (76%), worsening of disease (14%) and other reasons (10%).
      Overall, 31% of patients were NAb positive and 17% had titres high enough to
      obliterate IFNbeta bioactivity. The frequency of NAbs was similar in patients in
      the routine testing group compared with the worsening group. Samples showing high
      titres failed to be associated with worsening of symptoms. The study failed to
      show low NAb levels in patients responding poorly to IFNbeta. It is concluded
      that it is not possible to predict NAb status by clinical impression of treatment
      response. This is likely to be an effect of the partial efficacy of IFNbeta. Thus
      routine testing for NAbs must be carried out in order to identify NAb status in
      patients with MS.

PMID- 19094454
TI  - The relationship between intra-operative ultrasonography and pathological grade
      in cerebral glioma.
AB  - The value of intra-operative ultrasound as a tool in guiding resection of
      cerebral gliomas and the relationship between the appearance of brain tissue on
      intra-operative ultrasonography and pathological grade of cerebral glioma were
      investigated in 98 patients who underwent neurosurgical tumour removal. Lesions
      were classified according to pathological grade. Intra-operative ultrasonography
      orientated all the cerebral gliomas accurately and helped the neurosurgeon in
      assessing the tumour prior to removal. All lesions were hyperechoic compared with
      normal brain tissue, and the majority of lesions displayed irregular shapes and
      indistinct margins. Different pathological grades of glioma presented different
      ultrasonographic appearances. The majority of low-grade (I and II) cerebral
      gliomas were homogeneous, with distinct margins and clear surrounding oedema
      compared with adjacent brain tissue. High-grade (III and IV) cerebral gliomas
      mostly exhibited poorly defined borders and central necrosis, and the surrounding
      oedema was difficult to distinguish from the lesions. Residual tumour or
      haematoma were identified. In conclusion, intra-operative ultrasonography is of
      great value in locating and assessing the grade of cerebral glioma, and is
      conducive to enabling early evaluation and total removal of the lesion.

PMID- 19094455
TI  - Primary amelanotic malignant melanoma of the parotid gland: a case report.
AB  - Amelanotic malignant melanoma in the oral region is extremely rare and has not
      previously been reported in the parotid gland. This present case report describes
      an amelanotic malignant melanoma in the parotid gland, with no other primary
      lesion detectable. The medical history, pathology and immunohistochemical
      analysis of the case are described and the relevant literature is reviewed in
      order to help in the recognition of this uncommon tumour. Amelanotic malignant
      melanoma is a melanoma subtype with little or no pigmentation and, because of
      this lack of pigmentation and its wide-ranging clinical appearance, it often
      defies clinical diagnosis. A high level of vigilance is, therefore, necessary in
      diagnosing such a tumour in the parotid gland. Where it is suspected, positive
      expression of S-100 protein and human melanoma black 45(HMB45) using
      immunohistochemical analysis can be considered reliable methods of confirming
      diagnosis.

PMID- 19094456
TI  - Clear lens phacoemulsification with continuous curvilinear capsulorhexis and
      foldable intraocular lens implantation for the treatment of a patient with
      bilateral anterior lenticonus due to Alport syndrome.
AB  - The case of a 29-year-old man is reported who presented with a gradually
      progressive, painless decrease in vision over 10 years. Anterior segment
      examination with a slit lamp revealed anterior lenticonus in both eyes. The
      patient had previously been diagnosed with bilateral sensorineural deafness,
      however investigations revealed microscopic haematuria and renal insufficiency
      that subsequently led to a diagnosis of classical Alport syndrome. Since the
      patient's quality of vision was severely affected by the bulging anterior lens
      capsule, surgical treatment was required. Clear lens phacoemulsification with
      continuous curvilinear capsulorhexis and foldable intraocular lens implantation
      were performed in each eye 2 days apart. One week after surgery, visual acuity
      was excellent in both eyes. Clear lens phacoemulsification with continuous
      curvilinear capsulorhexis and foldable intraocular lens implantation was a safe
      and effective therapeutic choice in this patient for the management of anterior
      lenticonus due to Alport syndrome.

PMID- 19094457
TI  - True hermaphroditism.

PMID- 19094459
TI  - [Helicobacter pylori infection and cytokine gene polymorphisms of host in the
      development of gastric carcinoma].

PMID- 19094458
TI  - Haemostatic actions of the folkloric medicinal plant extract Ankaferd Blood
      Stopper. J Int Med Res 2008; 36:163-170.

PMID- 19094460
TI  - [Diagnosis and differential diagnosis of gastric lymphoproliferative disorders].

PMID- 19094461
TI  - [Hypomethylation of 5'CpG island of insulin-like growth factor binding protein
      related protein 1 is associated with its overexpression in colorectal cancer].
AB  - OBJECTIVE: To investigate the methylation status of 5'CpG island of insulin-like
      growth factor binding protein-related protein 1 (IGFBP-rP1) in colorectal cancer
      and its relationship with gene expression and clinicopathologic parameters.
      METHODS: Semi-quantitative reverse transcription-PCR (RT-PCR) was used to detect
      the expression of IGFBP-rP1 in 46 cases of colorectal cancer and their matched
      normal mucosa. Methylation-specific PCR (MSP) was applied to evaluate the
      methylation status of 5'CpG island of IGFBP-rP1. Colon cancer cell lines LoVo and
      SW620 were treated with demethylation agent 5-aza-2'-deoxycytidine (5-aza-dC),
      followed by RT-PCR and MSP detection. RESULTS: At the mRNA level, the expression
      of IGFBP-rP1 was higher in colorectal cancer tissue than that in the matched
      normal mucosa (P < 0.05). IGFBP-rP1 was methylated in 28/46 (60.9%) cases of
      colorectal cancer and 37/46 (80.4%) matched normal mucosa samples (P < 0.05). A
      negative correlation was found between IGFBP-rP1 expression and its methylation
      status. The expression of IGFBP-rP1 was restored in LoVo and SW620 after
      treatment with 5-aza-dC and MSP confirmation of its demethylation status. No
      relationships was found between the methylation status and clinicopathologic
      parameters. CONCLUSIONS: IGFBP-rP1 expression is negatively correlated with its
      methylation status in colorectal cancer. DNA methylation is one of the mechanisms
      regulating the expression of IGFBP-rP1. Hypomethylation of IGFBP-rP1 gene with
      its overexpression plays an important role in the initiation and development of
      colorectal cancer.

PMID- 19094462
TI  - [Clonality and Ki-67 protein expression in gastric carcinoma and precancerous
      lesions].
AB  - OBJECTIVE: To study the clonality of gastric carcinoma and precancerous lesions
      and its relationship with Ki-67 protein expression. METHODS: Formalin-fixed
      paraffin embedded tissues were collected from 174 cases of gastric endoscopic
      biopsies and surgical removed specimens. The lesional tissues were isolated by
      Laser Capture Microdissection. Methylation sensitive restriction enzyme (HpaII)
      digestion and polymerase chain reaction (PCR) were used to detect the clonality
      at the polymorphic human androgen receptor gene locus on the X chromosome. PCR
      products were analyzed by capillary electrophoresis using applied Biosystems 3730
      DNA Analyzer. In addition, a two-step immunohistochemical staining EnVision
      method was used to detect the expression of Ki-67 protein. RESULTS: The frequency
      of detection of monoclonality and expression rate of Ki-67 were found increased
      in a stepwise fashion from gastrointestinal metaplasia, low grade intraepithelial
      neoplasia, high grade intraepithelial neoplasia to intestinal carcinoma (15.63%,
      5/32; 22.22%, 10/45; 69.44%, 25/36 and 100.0%, 20/20; respectively). The presence
      of clonal proliferation was correlated with Ki-67 expression in low grade
      intraepithelial neoplasia (P < 0.01). CONCLUSIONS: The presence of clonal
      proliferation and increased Ki-67 are increasingly detected in the lesions along
      the multi-step gastric carcinogenesis model. Clonal status is associated with the
      expression rate of Ki-67 to a certain extent, suggesting a combined application
      of both markers may be useful in assessing early stages of gastric carcinoma.

PMID- 19094463
TI  - [Clonality analysis and mutational status of IgVH gene in Hodgkin variant of
      Richter syndrome].
AB  - OBJECTIVE: To detect the clonal relationship, the rearrangement, and the
      mutational status of IgVH gene; the influence of these molecular characteristics
      on the clinical outcome in Hodgkin variant of Richter syndrome; and the possible
      molecular pathogenesis in this transformation. METHODS: The clonal rearrangements
      and mutational status of IgVH genes were analyzed in Hodgkin variant of Richter
      syndrome and B-CLL with Reed-Stemberg (R-S)-like cells by GeneScan analysis and
      sequencing. Semi-nest PCR based on laser capture microdissection was utilized to
      compare the clonal relationship between B-CLL and R-S/R-Slike cells.
      Immunohistochemical staining was used to detect the different expressions of
      ZAP70, p53, IRF-4 and LMP1 in the two components. RESULTS: (1) 5/6 B-CLL cases
      transformed to Hodgkin lymphoma (HL)/R-S-like cells carried the mutated IgVH
      genes; (2) 2 cases of R-S cells and 1 case of R-S-like cells were clonally
      distinct from B-CLL clone and express LMP1, whereas 1 case of R-S-like cells was
      relating to the surrounding B-CLL cells and did not express LMP1; (3) 2/6 B-CLL
      cases transformed to HL convey VH4-34 and VH3-48 respectively. CONCLUSIONS: (1)
      Richter transformation to HL/R-S-like cells evolves from the B-CLL which
      originates from the germinal center or post germinal center B cells, indicating
      that different lymphoma cells of different subtypes in Richter syndrome come from
      different B cell lineage and possibly involve a different pathogenesis and
      pathway; (2) HL and R-S-like cells evolve from either the B-CLL clone or may
      develop as a clonally unrelated lymphoma, the independent secondary malignancies
      are appear to be EBV-positive, possibly as a consequence of the underlying
      immunodeficiency; (3) The biased usage of IgVH genes suggested a role of antigens
      involved in the HL variant of Richter syndrome.

PMID- 19094464
TI  - [Significance of expression of stromal cell derived factor 1 and CXCR4 in
      invasive breast cancer].
AB  - OBJECTIVE: To study the expression of stromal cell derived factor 1(SDF-1)/CXCR4
      and their association with clinicopathologic features and lymph node metastasis
      in invasive breast carcinoma. METHODS: The expression of SDF-1 was studied by
      immunohistochemistry and in-situ hybridization. Immunohistochemical study for
      CXCR4 was also performed. The correlation with various clinicopathologic
      parameters was analyzed. RESULTS: (1) SDF-1 was mainly expressed in tumor cells
      and the level of its expression (both membranous and cytoplasmic) in lymph node
      positive group was higher than that in lymph node-negative group (P = 0.033).
      Only cytoplasmic expression correlated with the number of positive lymph node
      involved by metastasis, TNM tumor stage, histologic grade, tumor dimension and
      estrogen receptor status (P < 0.05). (2) SDF-1 protein was also detected in the
      endothelial cells, although its mRNA was rarely detected. SDF-1 staining in
      lymphatics was associated with positive lymph node (P = 0.005) and SDF-1 staining
      in blood vessels correlated with stromal lymphocytic reaction (P = 0.001). The
      extent of nodal involvement was higher in the group with positive SDF-1 staining
      in blood vessels and with prominent lymphocytic reaction than that in other
      groups with one or neither of the two features (P < 0.05). (3) On the other hand,
      CXCR4 was mainly expressed in tumor cells (both nuclear and cytoplasmic); and the
      level of its expression in lymph node-positive group was higher than that in
      lymph node-negative group (P = 0.005). Only cytoplasmic expression correlated
      with the number of positive lymph node involved by metastasis, TNM tumor stage,
      histologic grade, tumor dimension and HER2 status (P < 0.05). The nuclear
      expression of CXCR4 was only correlated with progesterone receptor status (P <
      0.01). The cytoplasmic expression CXCR4 also positively correlated with SDF-1
      expression (P = 0.001). CONCLUSIONS: SDF-1 and CXCR4 can serve as biomarkers for
      diagnosis and prediction of lymph node metastasis, as well as potential
      therapeutic targets in invasive breast carcinoma. The difference in localization
      and staining patterns may also carry different significance.

PMID- 19094465
TI  - [Comparative genomic hybridization: the profile of chromosomal imbalances in
      rhabdomyosarcoma].
AB  - OBJECTIVE: To characterize the profile of chromosomal imbalances of
      rhabdomyosarcoma(RMS). METHODS: Comparative genomic hybridization (CGH) was used
      to investigate genomic imbalances in 25 cases of primary RMS including 10 cases
      of alveolar rhabdomyosarcoma (ARM), 12 cases of embryonic rhabdomyosarcoma
      (ERMS), 3 cases of polymorphic rhabdomyosarcoma (PRMS) and 2 RMS cell lines (A240
      originated from ARMS and RD from PRMS), with correlation to histological type,
      pathologic grading, clinical staging, gender and age, respectively. RESULTS: All
      twenty-five rhabdomyosarcomas showed evidence of increased or decreased DNA
      sequence copy numbers involving one or more regions of the genome. (1) The
      frequently gained chromosome regions in RMS were 2p, 12q, 6p, 9q, 10q, 1p, 2q,
      6q, 8q, 15q, 18q, and the frequently lost chromosome regions were 3p, 11p, 6p.
      (2) The frequently gained chromosome arms in ARMS were 12q, 2p, 6, 2q, 4q, 10q,
      15q. The frequently lost chromosome arms were 3p, 6p, 1q, 5q. The frequently
      gained chromosome regions in ERMS were 7p, 9q, 2p, 18q, 1p, 8q. The frequently
      lost chromosome arms in ERMS were 11p. (3) The frequently gained chromosome arms
      in translocation associated RMS were 12q, 2, 6, 10q, 4q and 15q (> 30%), 3p, 6p,
      5q (> 30%) were the frequently loss chromosome arms. The frequently gained
      chromosome regions in non-translocation associated RMS were 2p, 9q, 18q (> 30%),
      and 11p, 14q (> 30%) were the frequently loss chromosome regions. Gain of 12q was
      significantly correlated with the translocation-associated tumors (P < 0.05). (4)
      Gains of 9q was significantly correlated with clinical staging (P < 0.05).
      CONCLUSIONS: Gain of 2p, 12q, 6p, 9q, 10q, 1p, 2q, 6q, 8q, 15q, 18q and loss of
      3p, 11p, 6p may be involved in the tumorigenesis of RMS. Gains of 12q may be
      correlated with gene fusion/chromosomal translocation in ARMS. Gains of 9q may be
      correlated with an early tumor stage of RMS.

PMID- 19094466
TI  - [Transforming growth factor beta1 regulation of epithelial-mesenchymal transition
      in esophagus squamous cell carcinoma].
AB  - OBJECTIVE: To study the functional role of transforming growth factor
      beta1(TGFbeta1) in the regulation of epithelial-mesenchymal transition (EMT) and
      the effect of TGFbeta1-ASODN blockage of EMT in esophagus squamous cell
      carcinoma. METHODS: Esophageal squamous cell carcinoma cell line EC9706 was
      transfected with chemically synthesized TGFbeta1-ASODN. RT-PCR,
      immunohistochemistry and flow cytometry were used to detect the protein and mRNA
      expressions of TGF-beta1, E-cadherin and vimentin before and after the
      transfection. Morphological changes were documented and scarification test was
      used to detect the migration potential of EC9706 before and after the
      transfection. RESULTS: After TGFbeta1-ASODN transfection, mRNA (0.25 +/- 0.07)
      and protein (35.07% +/- 1.42%) expressions of TGFbeta1 in EC9706 were
      significantly lower than those before transfection (mRNA: 0.43 +/- 0.09; protein:
      43.57% +/- 1.77%, chi(2) = 13.847 and chi(2) = 84.120, P < 0.05). The mRNA (0.38
      +/- 0.09) and protein (17.13% +/- 1.45%) expressions of E-cadherin were
      significantly higher than those before transfection (0.22 +/- 0.06; 12.53% +/-
      1.31%, chi(2) = 0.160 and chi(2) = 40.008, P < 0.05) and the mRNA (0.73 +/- 0.07)
      and protein (14.15% +/- 1.46%) expressions of vimentin were significantly lower
      than those (0.89 +/- 0.09; 17.97% +/- 1.42%) before transfection (chi(2) = 0.160
      and chi(2) = 21.103, P < 0.05). Scarification test showed that after
      transfection, the mobility of EC9706 was significantly inhibited and its
      migration length (0.45 +/- 0.05) was significantly shorter than that before the
      transfection (0.81 +/- 0.11, chi(2) = 16.854, P < 0.05). CONCLUSIONS: TGFbeta1
      may contribute to EMT in esophageal squamous cell carcinoma. TGFbeta1-ASODN leads
      to an over-expression of E-cadherin and a down-regulation of vimentin, along with
      the morphological alterations and migration inhibition, indicating that a
      blockage of TGFbeta1 suppresses EMT in esophagus squamous cell carcinoma.

PMID- 19094467
TI  - [Effect of human p53 minigene with different 175 structures on gastric cancer
      cells].

PMID- 19094468
TI  - [ERCC1 mRNA expression levels and outcome of gastric cancer patients receiving
      oxaliplatin-based chemotherapy].

PMID- 19094469
TI  - [Expression of estrogen receptor and transforming grouth factor in bones of
      ovariectomized rats].

PMID- 19094470
TI  - [Correlation between mutational types and targeted treatment in gastrointestinal
      stromal tumors].

PMID- 19094471
TI  - [mircoRNA and gastric cancer: an update].

PMID- 19094472
TI  - [Research advances and application of molecular genetics in renal pathology].

PMID- 19094473
TI  - [Tumour of the uterus].

PMID- 19094474
TI  - [Duodenal ulcer with cryptococcus neoformans infection: report of a case].

PMID- 19094475
TI  - [Sex cord-like tumours exhibiting prominent Leydig cell differentiation: report
      of a case].

PMID- 19094476
TI  - [Fibroleiomyomatous hamartomas of lung: report of a case].

PMID- 19094477
TI  - [Comments on quantitative and qualitative analysis and applications of
      immunohistochemistry technology developed in China.].

PMID- 19094478
TI  - [Brief comments on the differences in pathology between Japan and China.].

PMID- 19094479
TI  - [Biography of James Paget.].

PMID- 19094480
TI  - [Genes and pathology].

PMID- 19094481
TI  - [Roles of DNA repair genes in pathogenesis and treatment of glioma].

PMID- 19094483
TI  - [Diagnostic value of SYT-SSX fusion gene detection by fluorescence in-situ
      hybridization for synovial sarcoma].
AB  - OBJECTIVE: To establish a method of SYT-SSX fusion gene detection by FISH and to
      explore its diagnostic value for synovial sarcoma. METHODS: The presence of SYT
      SSX fusion gene was determined by FISH using a tissue microarray containing 62
      known synovial sarcomas, 60 non-synovial sarcomas and 133 equivocal synovial
      sarcomas. FISH results were compared with those of RT-PCR published previously.
      RESULTS: Overall, 96.9% (247/255) of the cases were successfully analyzed by
      FISH. The sensitivity of FISH for known synovial sarcomas was 96.7% (58/60), and
      the specificity for the non-synovial sarcoma was 100% (59/59). Moreover, SYT-SSX
      gene fusion was detected in 78.1% (100/128) of the equivocal synovial sarcomas.
      The concordance rate between FISH and RT-PCR was 83.6% (102/122) in those
      equivocal synovial sarcomas, and overall 79.7% (106/133) of these cases were
      confirmed as synovial sarcomas either by RT-PCR or by FISH. CONCLUSIONS: The
      sensitivity and specificity of FISH detection of SYT-SSX fusion gene are high.
      FISH and RT-PCR are complementary to each other in the confirmation of synovial
      sarcomas, particularly those questionable cases.

PMID- 19094482
TI  - [Status of gene mutation and copy number of EGFR in 290 cases of non-small cell
      lung carcinoma].
AB  - OBJECTIVE: To investigate EGFR mutations and gene copy number status in non-small
      cell lung carcinomas in the Chinese patients. METHODS: Using formalin fixed and
      paraffin embedded tissue samples, EGFR mutations were investigated in 290 cases
      of non-small cell lung carcinomas by microdissection and scorpions amplification
      refractory mutation system. The status of EGFR gene copy number was investigated
      by FISH. Furthermore, the relationship between EGFR mutations and gene copy
      number, and the relationship between EGFR gene status and clinicopathological
      variables of non-small cell lung carcinoma were analyzed. RESULTS: The overall
      mutation rate of EGFR was 41.7% (121/290). The mutation rates in adenocarcinoma,
      large cell carcinoma and squamous carcinoma were 48.4%, 16.7% and 0,
      respectively. Ninety-two of 121 cases with mutations had exon 19 deletion and
      L858R mutation, and 6 tumors contained both types of the mutation. The overall
      FISH positive rate of EGFR was 51.2% (107/209). FISH positive rates in
      adenocarcinoma, large cell carcinoma and squamous carcinoma were 52.1%, 75.0% and
      11.1%, respectively. Therefore, EGFR mutations mainly occurred in the
      adenocarcinoma, and was significantly correlated with EGFR high copy number.
      CONCLUSIONS: There are higher EGFR mutation rate and FISH positive rate in non
      small cell lung carcinoma in Chinese patients. Combined analysis of EGFR mutation
      and gene copy number by FISH may provide a superior approach in selecting
      patients who may benefit anti-EGFR target therapy.

PMID- 19094484
TI  - [Myositis ossificans: a clinicopathologic analysis of 15 cases].
AB  - OBJECTIVE: To study the clinicopathologic features, diagnosis and differential
      diagnosis of myositis ossificans (MO). METHODS: The clinical features, radiologic
      results and pathologic findings of 15 cases of MO (including biopsy and surgical
      specimens) were analyzed. The hematoxylin and eosin sections were reviewed under
      light microscope. Immunohistochemical staining for S-100 protein, vimentin,
      desmin, actin and osteonectin was performed. RESULTS: The age of the patients
      ranged from 12 to 46 years. The male-to-female ratio was 11:4. Thirteen cases
      were located in the parosteum of long bone or subperiosteal soft tissue. The
      remaining two cases occurred in iliac region and palm, respectively. Five
      patients had history of injury, while 2 patients had operation before. Four
      patients had no history of trauma and the remaining one had unknown clinical
      history. Histologically, zonation pattern was not conspicuous in 10 biopsy cases
      and 8 corresponding surgical specimens. On the other hand, zonation pattern was
      observed in 5 biopsy cases and 7 corresponding surgical specimens. Follow up
      revealed relapses in two patients. Immunohistochemical study showed various
      degree of positivity for vimentin, desmin, actin and osteonectin. S-100 protein
      was focally positive in 2 of the cases. The Ki-67 index varied from 1% to 10%.
      CONCLUSION: Correct diagnosis of MO relies on correlation of clinical features,
      radiologic examination and pathologic findings.

PMID- 19094485
TI  - [Intraductal papillary mucinous neoplasm of pancreas: a clinicopathologic and
      immunohistochemical study of 19 cases].
AB  - OBJECTIVE: To study the clinicopathologic features and diagnosis of intraductal
      papillary mucinous neoplasm (IPMN) of the pancreas. METHODS: Nineteen cases of
      IPMN encountered during the period from 1999 to 2007 were studied by light
      microscopy and immunohistochemistry. RESULTS: IPMN occurred more often in males
      (68%). It affected patients in older age group (mean age = 59) and was located
      mainly in the head of pancreas (60%). The mean tumor size was 4.2 cm (range = 1
      to 8 cm). The clinical presentation was epigastric pain (53%), weight loss (32%),
      diabetes (21%), pancreatitis (21%) and jaundice (10%). Pancreatectomy was
      performed in 18 cases. The remaining patient received bypass surgery only.
      Features of in-situ or invasive malignancy were present in 15 of the 19 cases
      (78%). Histologically, the tumor consisted of papillary proliferations protruding
      into and expanding the pancreatic ducts. Invasion into the surrounding pancreatic
      parenchyma was noted in 12 cases and chronic pancreatitis was present in 16
      cases. Follow-up data (4 to 48 months) were available in 13 patients. Apart from
      1 patient who died of other disease, all were still alive. Immunohistochemical
      study showed that p53 was positive in 6 cases, p16 in 5 cases and fascin in 8
      cases. The expression of c-erbB-2 was all negative. Ki-67 index ranged from 1% to
      80% (mean = 38%). CONCLUSIONS: Malignant changes are not uncommon in IPMN. The
      prognosis after surgical resection however is better than that of conventional
      pancreatic adenocarcinoma. The overexpression of p53, p16 and fascin may be
      related to tumor progression. The possibility of malignant transformation needs
      to be considered if the Ki-67 index is over 15%. Early recognition by radiologic
      examination (including ERCP) and pancreatic cytology would be helpful in early
      diagnosis. Surgical resection represents the mainstay of treatment and long-term
      post-operative follow up is needed.

PMID- 19094486
TI  - [Interdigitating dendritic cell sarcoma/tumor: a study of 3 cases].
AB  - OBJECTIVE: To study the pathologic features, diagnosis and differential diagnosis
      of interdigitating dendritic cell sarcoma (IDCS). METHODS: The clinical findings,
      morphologic features and immunophenotype of 3 cases of IDCS were investigated.
      RESULTS: Gross examination showed that IDCS had a greyish-white to greyish-yellow
      cut surface. The site of occurrence included lung, spleen (with lymph node
      metastasis) and lymph node. Histologically, the tumor cells were arranged in
      nests, fascicles and whorls, with intimate admixture of many lymphocytes and
      plasma cells. They were oval to spindle in shape and contained pale eosinophilic
      cytoplasm, oval and sometimes grooved nuclei, small distinct nucleoli and ill
      defined cell borders. Immunohistochemical study showed that the tumor cells
      expressed S-100 protein. CONCLUSIONS: IDCS is a rare type of histiocytic and
      dendritic cell malignancy with distinctive morphologic findings. It needs to be
      distinguished from follicular dendritic cell sarcoma, inflammatory pseudotumor,
      Langerhans' cell histiocytosis, malignant melanoma, undifferentiated carcinoma
      and anaplastic large cell lymphoma. Immunohistochemical staining for S-100
      protein is helpful in confirming the diagnosis.

PMID- 19094487
TI  - [Expression of myocardin in differentiation of bone marrow-derived mesenchymal
      stem cells to smooth muscle cells].
AB  - OBJECTIVE: To investigate the expression profiles of myocardin gene during the
      differentiation of bone marrow-derived mesenchymal stem cell to smooth muscle
      cells in the conditional medium combined with a high concentration of fetal
      bovine serum (FBS). METHODS: Marrow-derived mesenchymal stem cells were isolated
      and purified from mouse femoral bone and shinbones using differential adherent
      methods. Cells at the third passage were induced by 20% FBS in conditioned
      medium, conditioned medium alone, 20% FBS or 10% FBS alone respectively. Mouse
      aortic smooth muscle cells were cultured as the positive control. Levels of mRNA
      and protein expression of myocardin and several smooth muscle cells marker genes
      were determined by immunofluorescence, RT-PCR and Western blot before and 3, 7,
      10, 14 d after the induction. The presence of smooth muscle myofilaments was
      detected by using transmission electron microscope. RESULTS: Naive bone marrow
      derived mesenchymal stem cells displayed multiple morphological forms including
      fusiform, polygon, oval, and micro-spherical, as compared to the single macro
      spindle form after the induction. Typical appearance of peak valley was displayed
      on the 21st day after induction. At the same time, the expression of smooth
      muscle marker genes was reinforced along with an up-regulation of myocardin
      expression. Immunofluorescence study showed that the cells expressing myocardin
      and smooth muscle marker genes such as alpha-SMA and SM-MHC increased.
      Fluorescence domain of myocardin translocated from cytoplasm to nucleus and the
      amounts of double positive cells for myocardin with alpha-SMA or SM-MHC also
      increased. RT-PCR confirmed that the mRNA expression of myocardin increased
      gradually and remained stabilized after achieving its peak on the 7th day after
      induction. The expression of smooth muscle marker genes, alpha-SMA and SM22alpha,
      remained stable on the 10th day of induction. It was also confirmed by Western
      blot that the protein expression of both myocardin and alpha-SMA were markedly
      increased during the induction. Finally, transmission electron microscopy
      revealed the presence of myofilament on the 21st day after induction.
      CONCLUSIONS: Bone marrow-derived mesenchymal stem cells can be effectively
      induced into smooth muscle-like cells by conditioned medium combined with 20%
      FBS. Myocardin plays an important role in the differentiation process of bone
      marrow-derived mesenchymal stem cells to the peripheral smooth muscle cells.

PMID- 19094488
TI  - [Expression and implication of angiotensin II type 1 receptor in myocardial
      fibrosis of rats].
AB  - OBJECTIVE: To investigate the expression and pathobiological implications of
      angiotensin II type 1 receptor (AT1R) in development of myocardial fibrosis of
      rats. METHODS: Rat myocardial necrosis model was established using isoproterenol
      injection (15 mg/kg). Rat serum aspartate transaminase (AST), lactate
      dehydrogenase (LDH), creatine kinase (CK) and creatine kinase isoenzymes (CK-MB)
      were detected by MD-100 automatic biochemical analyzer. Masson staining was used
      to evaluate the morphological changes. The expression of AT1R protein was
      determined by immunohistochemistry and its mRNA expression was analyzed by RT
      PCR. The expression of collage type I and III was determined by
      immunohistochemistry. RESULTS: Serum LDH, CK and CK-MB reached their peaks at 4 h
      (chi2 = 16.90, P < 0.05), and AST achieved its peak in 6 h (chi2 = 16.90, P <
      0.05). AT1R mRNA expression was increased 2 - 12 h after isoproterenol injection,
      but no statistical significance (P > 0.05) was observed comparing with the
      control. However, a significant AT1R mRNA increase was present at 24 h and
      decreased gradually after 48 h, and back to the control level after 3 weeks.
      Protein expression of AT1R increased proportionally with the severity of the
      fibrosis. CONCLUSIONS: AT1R mRNA and protein expressions increase significantly
      during myocardial ischemia, and is closely correlated with the fibrosis. These
      findings indicate that AT1R may play an important role in the pathogenesis of
      myocardial fibrosis.

PMID- 19094489
TI  - [Diagnostic accuracy of fine needle aspiration biopsy of cervical lymph node: a
      study of 580 cases].
AB  - OBJECTIVE: Study on the diagnostic accuracy of fine needle aspiration biopsy of
      cervical lymph nodes and to discuss the reasons of making a misdiagnosis.
      METHODS: Five hundred and eighty cases of cervical lymph node fine needle
      aspiration biopsy were reviewed retrospectively. Among them, histologic findings
      were available in 161 cases. The cytologic and histologic diagnoses were
      compared. RESULTS: There were altogether 226 cases of reactive lymphoid
      hyperplasia, 202 cases of specific inflammation, 45 cases of malignant lymphoma
      and 107 cases of metastatic carcinoma. The concordance rate between the cytologic
      and corresponding histologic diagnoses was 94.4%. The primary foci of most cases
      with metastatic carcinoma could be delineated by reviewing the clinical and
      pathologic finding. Inadequate cellularity was the main reason of making
      misdiagnosis and useful diagnostic clues might be obtained by careful study of
      the clinical findings. CONCLUSIONS: Fine needle aspiration biopsy of cervical
      lymph node carries a high diagnostic accuracy. It provides important clues in
      guiding subsequent clinical management. However, for detailed subtyping of
      certain disease entities such as malignant lymphoma, surgical biopsy for
      histologic and immunohistochemical studies are required.

PMID- 19094490
TI  - [Significance of COX2 and beta-catenin expression in nephroblastoma].

PMID- 19094491
TI  - [Prognostic significance of immune cells in tumor microenvironment].

PMID- 19094492
TI  - [Focal adhesion kinase and tumors].

PMID- 19094493
TI  - [Cystic nephroma and mixed epithelial stromal tumor of kidney: evolution of
      terminology, controversies, pathologic features and differential diagnosis].

PMID- 19094494
TI  - [Development and comparison of novel double staining methods for myelin and
      axon].

PMID- 19094495
TI  - [Adult congenital cystic adenomatoid malformation of lung co-existing with
      carcinoid: report of a case].

PMID- 19094496
TI  - [Cystic adventitial degeneration of left external iliac vein: report of a case].

PMID- 19094497
TI  - [Mixed medullary-papillary thyroid carcinoma: report of a case].

PMID- 19094498
TI  - [Merkel cell carcinoma presenting as lymph node metastasis: report of a case].

PMID- 19094499
TI  - [Synchronous and metachronous carcinomas occurring in digestive tract: report of
      a case].

PMID- 19094506
TI  - [Pull-through transection and anastomosis for early lower rectal cancer using
      double stapling technique].
AB  - OBJECTIVE: To introduce the experiences of pull-through transection and double
      stapling anastomosis for early lower rectal cancer. METHODS: From May 2001 to
      March 2008, 25 patients with early stage lower rectal cancer were operated by
      using pull-through transection and double stapling anastomosis. The average
      distance between the dentate line and lower margin of the tumor is (3.2 +/- 0.5)
      cm (2.0 - 4.5 cm). The average tumor diameter is (2.8 +/- 0.8) cm (2.0 - 3.5 cm).
      RESULTS: The average distance between the lower margin of the tumor and
      transection line is (1.5 +/- 0.4) cm (1.1 - 2.2 cm). All the resection margins
      were negative. Eighteen cases of the anastomosis were above the dentate line, 0.3
      - 2.1 cm [(1.7 +/- 0.2) cm] and the other 7 were below, 0.1 - 0.5 cm (average 0.3
      cm). Anastomotic leakage occurred in 1 case, and cured with conservative
      treatment. Local recurrence occurred in 1 case (4.0%), liver metastasis in 3
      (12.0%) and lung metastasis in 2(8.0%), respectively. Mild fecal incontinence
      occurred in 7 cases. CONCLUSION: Compared with trans-abdominal transection of
      distal rectum in low anterior resection of rectal cancer, pull-through
      transection and anastomosis provides more precise control of the cutting line and
      simpler resection.

PMID- 19094507
TI  - [Preliminary clinical experience of transrectal ultrasonography in early rectal
      cancer].
AB  - OBJECTIVE: To evaluate the accuracy of transrectal ultrasonography (TRUS) in the
      assessment of the invasion depth of rectal cancer, and analyze the value of TRUS
      in diagnosis of early rectal cancer. METHODS: TRUS was performed preoperatively
      in 163 patients with rectal cancer, and the results was compared with the
      postoperative pathological findings according to TNM staging. The early rectal
      cancer was diagnosed if the lesion was limited to mucosa and submucosa. The tumor
      located in mucosa was defined as mucosal cancer, while as submucosal cancer when
      the tumor invading into submucosa. Sixteen cases were confirmed as early cancer
      by pathology after the operation. No patients received chemotherapy and
      radiotherapy before operation. RESULTS: The sensitivity of TRUS in the staging of
      the early rectal cancer was 87.5% (14/16), specificity was 98.6% (145/147), and
      the positive predictive value was 87.5% (14/16). The sensitivity of TRUS in
      predicting mucosal and submucosal cancer was 85.7% (6/7) and 66.7% (6/9),
      respectively. Sixteen patients with early rectal cancer were examined before and
      after filling rectum with water. After filling rectum, all tumors were visualized
      clearly, while 14 tumors were correctly diagnosed as early rectal cancer. Before
      filling rectum, only 6 tumors were visualized clearly, and 3 tumors were staged
      correctly. The ultrasonographic appearance of early rectal cancer manifested in
      two kinds: protruded and ulcerative, and most were protruded (81.6%).
      CONCLUSIONS: TRUS is a valuable imaging examination for diagnosis of early rectal
      cancer preoperatively. Visualization rate and diagnostic accuracy of early rectal
      cancer are improved dramatically after filling rectum with water.

PMID- 19094508
TI  - [Endoscopic therapy of adenomatous polyps and early-stage carcinomas of the colon
      and rectum].
AB  - OBJECTIVE: To assess the clinical efficacy of endoscopic treatment for colorectal
      adenomatous polyps and early-stage carcinomas. METHODS: Between January 2006 and
      October 2007, 245 patients with colorectal adenomatous polyps and early-stage
      carcinomas with lifting sign(+) were treated by such endoscopic techniques as
      polypectomy, endoscopic mucosal resection (EMR), endoscopic piecemeal mucosal
      resection (EPMR) and endoscopic submucosal dissection (ESD). RESULTS: Two hundred
      and fifty-three lesions ranged from 0.5 to 8.5 cm and the mean resected size was
      2.3 cm, of which 157 were smaller than 2 cm and 96 larger than 2 cm. Confirmed
      pathologically, 249 lesions were successfully resected and the resection rate was
      98.4% (249/253). None of patients had massive hemorrhage during the procedure and
      2 had delayed bleeding. 1 had a little free air in abdominal cavity, 2 patients
      had subcutaneous emphysema due to deep tearing of the muscle layer, all 3
      recovered after several days' conservative treatment. Visible perforation
      occurred in 4 cases during the dissection, of which 3 were typically closed with
      metallic endo-clip without surgical treatment, and 1 was managed surgically with
      obvious distention and much abdominal free air. The rate of resectional
      complication was judged to be 3.6% (9/253). Eight cases were transferred to
      surgery altogether after endoscopic procedure. Two hundred and thirty-one cases
      were followed up with confirmed healing of the large artificial ulcer after ESD
      except for local recurrence in 3 cases after EPMR. CONCLUSIONS: Endoscopic
      resection appears to be an efficacious procedure to treat adenomatous polyp and
      early-stage carcinoma and provide pathological information about the whole
      lesion. Measures should be taken to reduce the complication rate of endoscopic
      resection in the future.

PMID- 19094509
TI  - [Clinical results and prognostic analysis of local excision in lower rectal
      cancer].
AB  - OBJECTIVE: To analyze the results and the prognosis of local excision of lower
      rectal cancer, and investigate the proper indication of local excision for cure
      purpose. METHODS: The clinicopathological data of 76 patients with lower rectal
      cancer treated from February 1985 to October 2007 were analyzed. RESULTS: Sixty
      nine patients received transanal excision, 6 cases received trans-sacral excision
      and 1 case received trans-vaginal excision. Among the cases, 48 cases were ranged
      as T1 phase, 25 cases as T2, 3 cases as T3. The operation complication rate was
      7.9%, and the 30-day mortality rate post operation was 0. The local recurrence
      rate was 22.4% and the overall 5 year survival rate was 84.5%. The local
      recurrence was significantly related with T stage and resection margin status.
      The survival was significantly related with mucinous adenocarcinoma, resection
      margin status and lymphovascular invasion; and the resection margin and
      lymphovascular invasion was the independent factors affecting survival.
      CONCLUSION: Local excision was safe in early stage lower rectal cancer. Careful
      patient selection is the key of the operation. The proper indication of local
      excision is T1-2 without high risk factors (high histopathological grade,
      presence of lymphatic or vascular invasion, mucinous adenocarcinoma); and the
      cases with T2 phase tumor should undergo chemoradiotherapy after local excision.

PMID- 19094510
TI  - [Pathological manifestation and feasibility of conservative breast surgery after
      effective neoadjuvant chemotherapy for breast cancer].
AB  - OBJECTIVE: To investigate the pathological manifestation of the lesion as well as
      the feasibility of conservative breast surgery after neoadjuvant chemotherapy of
      patients with locally advanced breast cancer. METHODS: Clinic data of the 46
      patients treated by neoadjuvant chemotherapy effectively and surgical procedures
      from June 2003 to August 2007 were analyzed. All the patients were female, aged
      from 28 to 65 years old with a mean of 46.3 years old. The diameter of neoplasm
      was 7 to 13 cm. All the patients had been treated by neoadjuvant chemotherapy
      effectively and received modified radical mastectomy or Halsted radical
      mastectomy. The specimen slices were cut from 6 different directions taking the
      residual cancerous lesion as the center. RESULTS: Nineteen patients (41.3%) were
      concentrating contracted, with complete remission in 6 patients (31.6%) and
      residual focus in peripheral zone in 13 patients (68.4%). Twenty-seven patients
      (58.7%) responded in a sifter-like pattern. CONCLUSION: For most patients with
      locally advanced breast cancer treated by neoadjuvant chemotherapy effectively,
      their pathologic features are not up to the conservative breast surgery
      criterion, conservative breast surgery should be cautiously considered.

PMID- 19094511
TI  - [Clinical and pathological characteristics and treatment of elderly patients with
      breast cancer].
AB  - OBJECTIVE: To explore the clinical and pathological characteristics and treatment
      patterns and the factors influencing treatments of elderly patients with breast
      cancer. METHODS: From January 2001 to December 2006, 647 female breast cancer
      patients over 65 years old were treated. The clinical records were reviewed. All
      patients were divided into three groups according to age, including 65 to 69
      years old group, 70 to 74 years old group and 75 years or elder group. These 647
      patients accounted for 13.4% of all breast cancer patients undergoing surgery
      during the same period. Major pathological type was invasive ductal carcinoma
      (79.3%). The patients who had chronic comorbid diseases of other systems
      accounted for 54.7%. Five hundred and eighty-six patients underwent modified
      radical mastectomy, accounting for 90.6%. Two hundred and thirty-three patients
      underwent postoperative adjuvant chemotherapy, accounting for 36.0%. The
      differences of clinicopathological characteristics and treatment patterns between
      three groups were tested by Chi-square test. RESULTS: Older patients had more
      tumors with mucinous and other pathological types, less over-expression of
      Her2/Neu(+++), higher probability to have comorbidities, higher probability to
      undergo relatively conservative surgery, lower probability to receive
      postoperative chemotherapy, and higher probability to receive postoperative
      endocrine therapy alone. CONCLUSIONS: Breast cancer in the elderly exhibits
      distinctive clinical and pathological characteristics. Treatment patterns they
      received are related to age.

PMID- 19094512
TI  - [A study on the relationship between breast cancer molecular classification and
      prognosis].
AB  - OBJECTIVE: To investigate the relationship between breast cancer molecular
      classification and prognosis. METHODS: From January 2002 to December 2003, 708
      female primary breast cancer patients with a mean age of 53 years old were
      retrospectively analyzed. The classification of breast cancer was according to
      the immunohistochemical results of estrogen receptor (ER), progesterone receptor
      (PR) and human epidermal growth factor receptor (HER2) status. Molecular
      classification definitions included highly endocrine responsive, incompletely
      endocrine responsive, triple negative, and HER2 positive. The prognosis among
      different molecular classifications of breast cancer was investigated. The
      survival rates of different classifications were compared by Log-rank test.
      RESULTS: The proportion of highly endocrine responsive, incompletely endocrine
      responsive, HER2 positive and triple-negative breast cancer was 33.2% (235/708),
      23.6% (167/708), 21.3% (151/708) and 21.9% (155/708). The follow-up period were
      from 3 to 68 months with a median of 40.2 months. A total of 100 cases were
      identified to had disease recurrence or death. Factors affecting the prognosis
      were tumor size, axillary lymph node status, molecular classification, adjuvant
      radiotherapy and adjuvant endocrine therapy by univariate analysis. Multivariate
      analysis revealed that the molecular classification and lymph node status were
      the independent prognostic factors with the hazard ratio 1.205 (P = 0.047) and
      4.512 (P = 0.000), respectively. Survival analysis showed that highly endocrine
      responsive breast cancer was with superior prognosis versus others. CONCLUSIONS:
      Molecular classification of breast cancer is an independent predictor of
      prognosis. Breast cancer patients classified as highly endocrine responsive
      subtype have the best outcome.

PMID- 19094513
TI  - [A clinic study of cervical lymph node metastasis in well-differentiated thyroid
      carcinoma].
AB  - OBJECTIVE: To study the distribution of cervical lymph nodes metastasis and
      explore the surgical treating modality of cervical lymph nodes in the patients
      with differentiated thyroid carcinoma. METHODS: The clinic and pathological data
      of 104 patients with differentiated thyroid carcinoma who had undergone neck
      lymph nodes dissection from January 2003 to June 2007 were analyzed
      retrospectively. There were 29 male and 75 female patients. The age of the
      patients was 12 to 79 years old with a median of 39 years old. Patients were
      divided into clinic cervical lymph nodes metastasis (cN+) group and clinic no
      cervical lymph nodes metastasis (cN0) group according the condition of physical
      examination and image analysis preoperatively and compared respectively with
      pathological data postoperatively. RESULTS: In the cN+ group 91.3% (63/69)
      patients were pN+ while in the cN0 group 52.1% (25/48) patients were pN+. The
      distribution of metastasized lymph nodes: level VI 64.1%, level II 31.6%, level
      III 44.4%, level IV 40.2%, level V 12.0%, level I 3.2%. In the cN+ group 86.7%
      (54/63) patients with lymph nodes metastasis had multi-levels lymph nodes
      metastasis while in the cN0 group 64.0% (16/25) patients had single-level lymph
      nodes metastasis. CONCLUSIONS: Cervical lymph nodes metastasis in the patients
      with differentiated thyroid carcinoma mainly localize in level II, level III,
      level IV, level VI, especially level VI. Patients with lymph nodes metastasis had
      multi-levels lymph nodes metastasis in the cN+ group but single-level in the cN0
      group. The surgical treating modality of cervical lymph nodes should also be
      different in the two group patients.

PMID- 19094514
TI  - [The characteristics of papillary thyroid cancer lymph node metastasis and the
      clinical significance of central region cervical lymph node dissection].
AB  - OBJECTIVE: To explore the necessity of the central region cervical lymph node
      dissection for patients with papillary thyroid carcinoma. METHODS: Clinical data
      of 457 papillary thyroid cancer patients underwent bilateral thyroidectomy with
      cervical lymph node excision from June 2003 to September 2007 were
      retrospectively reviewed. There were 86 male patients and 371 female patients.
      The age was 17 to 73 years old. RESULTS: There were no death for operation or in
      hospital. The total rate of central region cervical lymph node (VI region)
      metastasis was 59.1% (270/457), and bilateral metastasis was 42.2% (114/270). The
      total rate of III + IV region cervical lymph node metastasis was 29.8% (136/457).
      For unilateral papillary thyroid cancer, when tumor diameter over 1 cm and tumor
      breaking through thyroid caps, the central region cervical lymph node metastasis
      was 64.5% (178/276) and 81.6% (120/147) respectively. When the tumor diameter <
      or = 1 cm and tumor confining in thyroid, central region cervical lymph node
      metastasis was 23.4% (11/47) and 39.2% (69/176) respectively. There were 5 cases
      with lymph node jumping metastasis. During the follow-up of 7 to 59 months, 1
      case died of lung metastasis. Four cases occurred local recurrence, 3 cases
      occurred distant metastasis. There was no case of hypothyroidism under the
      thyroxine replacement therapy. CONCLUSIONS: For papillary thyroid cancer, the
      most common cervical lymph node metastasis is central region. It is necessary to
      dissect bilateral central region lymph node following the original surgical
      procedures.

PMID- 19094515
TI  - [Continuous wave laser of 2 microm for bladder tumor treatment].
AB  - OBJECTIVE: To analyze the clinical characteristics of 2 microm continuous wave
      laser vaporization resection for the treatment of bladder tumors. METHODS: A
      total of 56 patients with 68 bladder tumors underwent 2 microm laser vaporization
      resection via a transurethral cystoscope under caudal anesthesia. In the
      operation, the wall of the urinary bladder was vaporized and cut, the muscular
      layers were removed, and then the specimens were sent for pathological inspection
      separately. The following variables were recorded: operation time, blood loss,
      complications during and after the operation, pathology staging of the tumors,
      and follow-up visit time. RESULTS: All patients endured the operation. The mean
      surgery time was 8.8 +/- 3.3 minutes (range, 4 to 15 minutes). Blood loss was
      minimal, no patient experienced an obturator nerve reflection, or a hemorrhage
      after the operation. The pathology staging of the tumors were as follows: 40
      cases (total 47 tumors) were T1 stage; 16 cases (total 21 tumors) were T2 stage.
      The follow-up periods were between 12 to 17 months, and the mean period was 14.5
      months. Tumor recurrences were found in 3 cases, and one patients suffered two
      recurrences, the total recurrence rate was 5.3%. There was no primary recurrence.
      CONCLUSIONS: The 2 microm continuous wave laser is a new, safe and efficacious
      method for the treatment of bladder tumors. Because the 2 microm laser can
      vaporize and cut the muscular layers of the bladder finely, it can not only treat
      superficial bladder tumors efficiently, but also treat some types of invasive
      tumors of the bladder.

PMID- 19094516
TI  - [Therapeutic clinical effect of radiofrequency ablation for small hepatocellular
      carcinoma in cirrhotic patients: a meta-analysis].
AB  - OBJECTIVE: To evaluate the value of radiofrequency ablation in the treatment of
      small hepatocellular carcinoma (HCC). METHODS: MEDLINE (1966 - 2008), EMBASE
      (1966 - 2008), CBMdisc (1978 - 2008) were searched. The Cochrane Library,
      Evidence Base Medicine Reviews (Ovid Edition), Cancerlit (1993 - 2008) and so on,
      date of last search: 30 January 2008. There were no restrictions in language.
      Randomized controlled trials (RCTs) and non-RCTs were both included in this
      study, and the quality of each included study was assessed. Meta-analysis was
      performed by RevMan 4.2 software. RESULTS: Four prospective controlled studies
      and two retrospective studies met the inclusion criteria. The results of meta
      analysis showed that 1-, 3-, 4-year survival rates and 1-year tumor-free survival
      rate had not statistically significant difference in RFA group compared with
      surgical resection group (P > 0.05), but surgical resection was more effective to
      improve 3-year tumor-free survival rate than RFA (P < 0.05). CONCLUSIONS: The
      effect of RFA therapy on small HCC is similar to resection, RFA could be
      considered as the first-line treatment of choice for surgical candidates with
      small HCC in cirrhotic patients.

PMID- 19094517
TI  - [The strategy of posterior decompression and re-establishing the insertion of
      extensor for ossification of posterior longitudinal ligament involved in C(2)].
AB  - OBJECTIVE: To investigate an approach of posterior cervical spinal canal
      decompression and re-establishing the insertion of extensor, aim at the
      ossification of the posterior longitudinal ligament (OPLL) involved in C(2).
      METHODS: From 2002 to 2006, 10 patients with OPLL involved in C(2) underwent open
      door laminoplasty, with the posterior cervical ligamentous complex and the
      insertion of extensor reconstructed on C(2), were reviewed retrospectively. The
      range of decompression was from C(2) to C(7). The sagittal diameter of C(2)
      vertebral canal, alignment of the cervical spine (C(2)-C(7) angle), and JOA score
      before and after operation were contrasted respectively. RESULTS: All patients
      were followed up, average 14 months. Before the operation, the average sagittal
      diameter of C(2) vertebral canal was 5.6 mm (4 - 8.8 mm), JOA score was 9.6
      scores (6 - 12 scores), C(2)-C(7) angle was 6.5 degrees (-2 degrees - 12 degrees
      ). After the operation, the average sagittal diameter of C(2) vertebral canal was
      13.4 mm (10 - 18.2 mm, P < 0.01), JOA score was 10.9 scores (8 - 14 scores) and
      the C(2)-C(7) angle was 7.4 degrees (3 degrees - 14 degrees ) in earlier.
      Finally, the JOA score was 13.2 scores (10 - 17 scores, P < 0.05), and the C(2)
      C(7) angle was 7.0 degrees (2 degrees - 15 degrees , P > 0.05) at last.
      CONCLUSIONS: The open-door laminoplasty, with an approach of the posterior
      cervical ligamentous complex and the insertion of extensor reconstructed, is an
      appropriate method for treating OPLL involved in C(2). This process keeps the
      cervical curve in a better way, and decompresses the spinal canal effectively.

PMID- 19094518
TI  - [Treatment and mechanism of cervical spondylosis with sympathetic symptoms].
AB  - OBJECTIVE: To evaluate the role of anterior decompression with resection of the
      posterior longitudinal ligament (PLL) on the cervical degenerative disease with
      sympathetic symptoms and to primarily validate our speculation on the mechanism
      of this entity. METHODS: Forty-seven cases suffered from cervical spondylosis
      from 2002 to 2007 were retrospectively reviewed. The inclusive criteria were: (1)
      cervical myelopathy or radiculopathy or both secondary to cervical degenerative
      disease; (2) complaining of unexplainable and irrelievable sympathetic symptoms
      such as dizziness, vertigo, etc; (3) performed with anterior cervical
      decompression with PLL resection and internal fixation. The JOA scores were
      recorded and evaluated. The sympathetic symptoms were evaluated by both 20 points
      evaluation system and patient's satisfaction evaluation. The posterior
      longitudinal ligaments of 8 rabbits were harvested and stained by Sucrose
      Phosphate-glyoxylic acid (SPG) to distinguish the sympathetic nerve fibers. The
      results were observed and evaluated by fluorescent microscope and Image-pro plus
      5.0. RESULTS: All the patients were followed up for 10 to 48 months. The JOA
      scores before operation were 12.6 and increased to 15.2 at the final follow up.
      The sympathetic symptoms evaluation was 6.0 before operation and 2.8 after. The
      satisfactory evaluation was excellent in 19 cases, good in 16, fair in 8 and poor
      in 4. The effective rate was 87.5%. The SPG stain showed that there were plenty
      of sympathetic post-ganglia fibers in the cervical PLL, which were distributed
      like a web, and there were more fibers distributed at the interspaced zone than
      at the vertebral body zone. The density of the sympathetic nerve fibers in the
      C(2/3), C(3/4) and C(4/5) were greater than those in C(5/6) and C(6/7); while the
      density in the shallow layer were greater than those in the deep layer.
      CONCLUSIONS: The sympathetic nerve fibers distributed in the cervical PLL maybe
      another one significant factor causing sympathetic symptom of cervical
      spondylosis. The anterior cervical decompression with resection of PLL can
      relieve the sympathetic symptoms of the patients.

PMID- 19094519
TI  - [Microsurgical treatment of gigantic dumbbell-shaped jugular foramen tumor].
AB  - OBJECTIVE: To discuss the method of microsurgical treatment for jugular foramen
      tumor (JFT). METHODS: Ten patients with dumbbell-shaped JFTs who were
      microsurgically treated by the same group were retrospectively studied, the
      surgical approaches includes infratemporal approach and modified far lateral
      approach according to tumors' size, blood feeding, hearing and growth manner.
      Cranial nerve function, pre- and postoperative complications, follow-up data were
      presented and discussed. RESULTS: Gross total tumor removal was achieved in 7
      patients, subtotal removal in 2 cases, partial removal in 1 case, postoperative
      cerebrospinal fluid leaking in 1 cases, postoperative new cranial nerve defects
      in 1 cases, aggravation in 2 cases. Postoperative deficits of the cranial nerves
      improved in 80 percent of the patients. Favorable facial function in 6 months
      postoperatively (House-Brackmann grade system in Grade 1 and Grade 2) was noted
      in 7 of the 10 patients. The postoperative level of hearing was preserved in 3 of
      the 6 patients with residual hearing. Recurrence was noted in 1 case during the
      follow-up period. CONCLUSIONS: Surgical total removal of JFT is possible depends
      on microsurgical operation with the two approaches with lowly additional
      neurological deficits. The function of preoperative affected cranial nerves can
      be recovered.

PMID- 19094525
TI  - [Clinical selection of endovascular stenting and carotid endarterectomy in
      treatment of carotid artery stenosis].
AB  - OBJECTIVE: To explore reasonable clinical decision in treating carotid artery
      stenosis under different conditions. METHODS: The data of 133 carotid artery
      stenosis patients were retrospectively analyzed. Of the patients, 46 cases were
      treated with carotid angioplasty and stenting (CAS), 87 patients received carotid
      endarterectomy (CEA). The length of hospital stay and National Institutes of
      Health Stroke Scale (NIHSS) grade before and after treatment in both groups were
      observed; the forward flow were assessed by digital subtraction angiography (DSA)
      before and after treatment; the degree of carotid artery stenosis were determined
      by using ultrasound during 3 to 24 months after treatment in both groups; the
      cumulative incidence of major cardiovascular events was concentrated, including
      appearance of death, stroke or myocardial infarction during 30 days after CAS and
      CEA and death or homonymy stroke during 31 days to 2 years. RESULTS: Significant
      difference was found in hospital stay and when NIHSS exceed 20 after treatment
      between the two groups (P < 0.05); there was no significant difference in the
      forward flow before and after treatment in both groups; the carotid artery
      stenosis had been improved significantly after the operation in both groups; the
      cumulative incidence of major cardiovascular events in CEA group was
      significantly higher than in CAS group in 30 days after the operation (P < 0.05),
      but no statistical difference in 31 days to 2 years after the operation.
      CONCLUSIONS: CAS and CEA has equivalent effects in treating carotid artery
      stenosis, and should be selected according to the location of stenosis,
      etiological factors and the condition of opposite carotid artery.

PMID- 19094526
TI  - [Diagnosis and long-term results of surgical resection of early cardiac
      adenocarcinoma].
AB  - OBJECTIVE: To summarize therapeutic experience and the long-term results of early
      cardiac adenocarcinoma with surgical resection. METHODS: Ninety cases were
      diagnosed with early cardiac adenocarcinoma during endoscopic screening in high
      incidence rate area of esophageal cancer from 1972 to 1997. All of the patients
      accepted surgical treatment. Cardiectomy included partial stomach and esophagus
      was performed through left thoracotomy in all patients. Esophagogastrostomy was
      carried out in the infra-aortic region and thoracoabdominal lymphatic dissection
      was performed in all cases. RESULTS: The resection rate was 100%. One patient
      died in one month after the operation. Postoperative complications occurred in 4
      cases (4.4%). Pathological examination of cancer specimens showed that 46 cases
      (51.1%) were intramucosal carcinoma without lymphatic metastasis and 44 cases
      (48.9%) were submucous infiltrating carcinoma with lymphatic metastasis in 5
      (11.4%). The patients were followed-up to 2002, and the overall 5, 10, 15, 20 and
      25 year survival rates were 91.9%, 83.6%, 69.6%, 49.8% and 16.6%, respectively.
      CONCLUSIONS: Early diagnosis and early treatment may be the best approach for
      promoting the survival of the cardiac cancer. Surgical resection of early cardiac
      carcinoma provides excellent long-term survival.

PMID- 19094527
TI  - [The local control of radiotherapy following Ivor-Lewis esophagectomy in the
      patients with stage II A middle-third thoracic esophageal cancer].
AB  - OBJECTIVE: To investigate the local control of radiotherapy following Ivor-Lewis
      esophagectomy in the patients with stage IIA middle-third thoracic esophageal
      cancer. METHODS: From June 1999 to June 2002, 125 patients with stage IIA
      squamous cell carcinoma of the middle-third thoracic esophagus were treated with
      Ivor-Lewis esophagectomy with two-fields lymphadenectomy. The survival rate was
      calculated by Kaplan-meier method and the difference of recurrence rate compared
      by chi(2) test. RESULTS: The 3-year and 5-year survival rates were 58.4% and
      43.2% in this group, respectively. Tumor recurrence occurred in 61 of the 125
      patients (48.8%) within 3 years after operation. Of all cases of recurrence, 38
      patients (30.4%) developed locoregional recurrence (including 5 patients with
      locoregional and hematogenous recurrence simultaneously). The locoregional
      recurrence rate of patients who received postoperative radiotherapy (20.3%) was
      significantly lower than that of both the group who received adjunctive
      chemotherapy (40.6%) and the group without adjunctive therapy (41.4%) (P < 0.05).
      CONCLUSIONS: About half of the patients would develop recurrence disease within 3
      years after Ivor-Lewis esophagectomy with two-fields lymph-adenectomy.
      Radiotherapy following Ivor-Lewis esophagectomy is an effective strategy to
      control local recurrence of the stage II A middle-third thoracic esophageal
      cancer.

PMID- 19094528
TI  - [Video-assisted minimally invasive cardiac surgery for atrial fibrillation: a
      report of 57 cases].
AB  - OBJECTIVE: To evaluate the feasibility and the efficacy of a new video-assisted
      minimally invasive surgery for patients with atrial fibrillation (AF). METHODS:
      From December 2006 to October 2007, 57 patients who were 56.4 years old in
      average underwent the video-assisted minimally invasive cardiac operation for AF,
      and there were 40 male patients. Thirty-eight patients were paroxysmal AF, 7
      patients were persistent and 12 patients were long-standing persistent. Three
      patients had failed catheter ablation, and two patients had preoperative
      permanent pacemaker implantation. All patients went under the minimally invasive
      procedure. Intraoperative electrophysiological mapping were performed. RESULTS:
      Mean operation time was 3.5 h. One patient was confirmed of left auricle
      thrombus, and one received concurrent epicardial cardiac resynchronization
      therapy during the procedure. There were no perioperative deaths. Acute
      respiratory failure occurred in 1 patient and acute heart failure in 1 patient
      after operation. Sixteen patients had electrical cardioversion after operation
      and during follow-up. At discharge, 78.9% (45/57) of all patients were in sinus
      rhythm (84.2% for paroxysmal AF, 71.4% for persistent AF, 66.7% for long-standing
      persistent AF). The patients were followed-up by 1 to 10 months. At 1 month after
      operation, overall 64.3% (36/56) were in sinus rhythm (67.6% for paroxysmal AF,
      57.1% for persistent AF, 58.3% for long-standing persistent AF). At 3 months,
      overall 83.9% (47/56) were in sinus rhythm (86.5% for paroxysmal AF, 85.7% for
      persistent AF, 75.0% for long-standing persistent AF). At > or = 6 months,
      overall 87.0% (20/23) were in sinus rhythm (89.5% for paroxysmal AF, 75.0% for
      persistent AF). No thromboembolic event was observed during follow-up period.
      CONCLUSION: The video-assisted minimally invasive cardiac surgery proves to be
      safe, less traumatic, and presents optimistic early outcomes for paroxysmal AF
      patients.

PMID- 19094529
TI  - [The use of a pneumatic tourniquet in total knee arthroplasty: a prospective,
      randomized study].
AB  - OBJECTIVE: To determine the value of the use of a pneumatic tourniquet in total
      knee arthroplasty. METHODS: Sixty patients were prospectively randomized into 2
      groups, one group underwent total knee replacement with a tourniquet (n = 30) and
      one without (n = 30). Operating time, blood loss, postoperative mean morphine
      requirement, swelling, ecchymosis, earlier straight-leg raising and postoperative
      knee flexion were measured in both groups. RESULTS: There was no significant
      difference in the total blood loss between the 2 groups although the
      intraoperative blood loss was significantly greater in those without a
      tourniquet. The mean morphine requirement, postoperative swelling, scope of
      ecchymosis, earlier straight-leg raising and postoperative knee flexion in the
      patients that had surgery without a tourniquet were significantly better than
      those with a tourniquet. CONCLUSION: Knee arthroplasty operation with the use of
      a tourniquet has only small benefits on the total blood loss, but hinder in
      patients' early postoperative rehabilitation exercises.

PMID- 19094530
TI  - [Clinical evaluation of adolescent lumbar disc herniation misdiagnosed as
      idiopathic scoliosis].
AB  - OBJECTIVE: To retrospectively review the clinical features and treatment strategy
      of lumbar disc herniation in adolescents initially misdiagnosed as idiopathic
      scoliosis. METHODS: From 1998 to 2007, nineteen adolescents with lumbar disc
      herniation were admitted to our hospital. All of them presented a scoliotic curve
      as their first complaint. There were 10 males and 9 females with the age ranged
      from 14 to 20 years. The disc herniation located at L(4,5) in 10 patients, at
      L(5)S(1) in 7, and at L(4)-S(1) in 2. The Cobb angle ranged from 23 degrees to 38
      degrees . The distance from the C(7) plumb line to the central sacral line
      averaged 4.7 cm. All the patients underwent conventional open discectomy,
      followed by a pelvic traction for 3 weeks. A cast fixation for one month was
      recommended for further correction of scoliosis if the curve improvement was not
      obvious. RESULTS: Fourteen (73.7%) patients had a disc herniation at the convex
      side of lumbar curve, and 5 (26.3%) patients had a disc herniation at the concave
      side, which showed a marginal statistical correlation between the side of the
      disc herniation and the direction of lumbar curve (P = 0.07). Leg pain and
      numbness disappeared in the 19 patients after surgical decompression. After the
      pelvic traction for 3 weeks postoperatively, the Cobb angle reduced to 14
      degrees, with the mean distance from the C(7) plumb line to the central sacral
      line of 2.2 cm. At a mean follow-up of 21 months, neither the recurrence of back
      pain and leg pain nor the loss of spontaneous scoliosis correction was found.
      CONCLUSIONS: Care should be taken to the diagnosis of lumbar disc herniation in
      adolescents with spine deformity as their chief complaint. Satisfactory clinical
      results can be achieved by early diagnosis and proper treatment.

PMID- 19094531
TI  - [Clinical research of delayed hyperextension injury concomitance spinal cord
      injury of cervical spine].
AB  - OBJECTIVE: To discuss Clinic feature and turnover of delayed hyperextension
      injury concomitance spinal cord injury of cervical spine. METHODS: The clinic
      data of 30 patients delayed hyperextension injury of cervical spine were reviewed
      and analyzed. Course of disease was from 3 months to 8 years. Thirty patients
      were divided into three groups according to course of disease. The first group, 3
      - 6 months, 17 cases; the second group, 6 - 12 months, 8 cases; the third group,
      12 months-8 years, 5 cases. Neurological function improvement rates were
      evaluated according to the JOA scores at preoperative, 3 months and 1 year post
      operation, and complications were observed in three groups. Twenty-six cases were
      treated with anterior decompression, bone graft and plate fixation. Four cases
      were treated with posterior decompression, bone graft and plate fixation.
      RESULTS: The patient number of the three group exist with statistical
      significance. Thirty patients were followed up for 18 - 39 months, 23 months on
      average. Neurological function recovery rates were 23.8% in the first group,
      53.9% in the second group and 54.3% in the third group at 1 year post operation.
      JOA scores of the first group and the second group with statistical significance
      at 3 months and 1 year post operation. JOA scores of the first group and the
      third group with statistical significance at 3 months and 1 year post operation.
      JOA scores of the second group and the third group without statistical
      significance at 3 months and 1 year post operation. CONCLUSIONS: Incidence of
      hyperextension injury associated with spinal cord injury of cervical spine would
      degrade along with course of disease prolong. If delayed spinal cord injury
      occurred earlier, the patient's condition was severer and badly improvement rate.

PMID- 19094532
TI  - [The role of initial bone mineral status in predicting the early outcome of brace
      treatment in girls with adolescent idiopathic scoliosis].
AB  - OBJECTIVE: To investigate whether initial bone mineral status acts as a predictor
      factor in evaluating the early outcome of brace treatment in adolescent
      idiopathic scoliosis (AIS) girls. METHODS: Seventy-seven girls with AIS, aged 10 
      15 years old, were included in this study. A standardized bracing protocol was
      performed in these girls, and the early outcomes of brace treatment were
      evaluated at over-1-year follow-up. Girls with a progressed scoliosis and those
      with a non-progressed scoliosis were identified. The associations between the
      outcome and the indices before bracing, including age, menstrual status, Risser
      grade, bone mineral density (BMD) status, curve magnitude and curve pattern were
      assessed using univariate analysis. A multiple Logistic stepwise regression was
      used to determine the risk factors in curve progression in AIS girls treated with
      brace treatment. RESULTS: There were 16 girls (21%) with a progressed scoliosis
      and 61 girls (79%) with a non-progressed scoliosis, respectively. In the girls
      with a progressed scoliosis, higher ratios of subjects were found with pre
      menarchal status (chi(2) = 9.628, P = 0.004), lower Risser grade (chi(2) = 4.565,
      P = 0.037), main thoracic scoliosis (chi(2) = 4.009, P = 0.045), a larger curve
      (chi(2) = 1.685, P = 0.194), as well as osteopenia (chi(2) = 3.828, P = 0.050),
      as compared with those with a non-progressed scoliosis. During brace treatment,
      besides pre-menarchal status, a larger Cobb angle, and a main thoracic scoliosis,
      osteopenia (OR = 5.362, P = 0.022) was identified as the risk factor in curve
      progression in AIS girls, as revealed by the multiple Logistic regression
      analysis. CONCLUSIONS: Osteopenia might be an independent risk factor in the
      curve progression during brace treatment. The analysis of initial BMD status
      before bracing may help to predict the outcome of brace treatment.

PMID- 19094533
TI  - [Analysis of the risk factors of postoperative renal failure of type A aortic
      dissection].
AB  - OBJECTIVE: To evaluate the risk factors of postoperative renal failure (RF) in
      the patients with type A dissection of aorta operated on with cerebral perfusion
      and deep hypothermia circulatory arrest (DHCA). METHODS: From January 2004 to
      October 2007, 157 patients with type A dissection of aorta underwent surgical
      procedures with cerebral perfusion and DHCA. There were 115 male patients and 42
      female patients with the age from 17 to 76 years old. Antegrade selective
      cerebral perfusion through axillary artery was performed for 129 patients and
      retrograde cerebral perfusion from superior cava vein was performed for 28
      patients. All the factors underwent univariate and multivariate analysis.
      RESULTS: Mean cardiopulmonary bypass duration was (188.0 +/- 10.8) min and mean
      cerebral perfusion time was (36.0 +/- 3.1) min. Fifteen patients died in hospital
      and the hospital mortality was 9.6%. Permanent neurological dysfunction (PND)
      occurred in 8 patients (5.1%). Postoperative RF was observed in 20 patients
      (12.8%). Multivariate analysis showed the preoperative renal dysfunction (P =
      0.042, OR = 4.41) and over seventy-year-old patients (P = 0.049, OR = 4.94) were
      found to be the risk factors of postoperative RF. There was a higher incidence of
      death (45%, P = 0.001) and PND (25%, P = 0.009) in the patients of postoperative
      RF when compared with the other patients. CONCLUSION: The preoperative renal
      dysfunction and elderly patients were found to be the risk factors of
      postoperative RF after type A dissection of aorta surgery.

PMID- 19094534
TI  - [Mechanical circulation support as emergency bridging for heart transplantation].
AB  - OBJECTIVE: To investigate the experience of patients in acute cardiogenic shock
      required insertion of mechanical circulation support devices (MCS) before
      undergoing standard pretransplant evaluations. METHODS: From February 2005 to
      August 2007, 10 patients including 7 male and 3 female required emergency
      bridging placement of MCS. Average age was (40 +/- 16.2) years old. Mean body
      weight was (70.8 +/- 18.1) kg. There were 5 patients of dilated cardiomyopathy, 2
      patients of arrhythmic right ventricular cardiomyopathy, 2 patients of ischemic
      cardiomyopathy and 1 patient of end-stage valvular heart disease. All patients
      were accompanied with acute decompensation of congestive heart failure. Before
      implantation of MCS, all patients received treatment of three or more inotropic
      drugs at maximal dosages, 6 patients suffered from ventricular tachycardia, 4
      patients required cardio-pulmonary resuscitation treatment and 3 patients
      suffered from definite function defect of liver and kidney. MCS included ECMO for
      8 patients, BVS5000 and MEDOS for 1 patient respectively. RESULTS: The duration
      of MCS supporting was 3 to 44 d with a mean of (11.5 +/- 13.9) d. Four patients
      were successfully supported for getting heart transplantation, 1 patient received
      kidney transplantation simultaneously. Two patients recovered from acute heart
      failure, discharged and remained on regular heart transplantation list. One
      patient died from cerebral embolism after 44 days' support and 1 died from
      multiple organ failure after 3 days' support. Because of severe infection, MCS
      treatment of 2 patients was terminated ahead of schedule by their family and the
      patients were lost finally. CONCLUSIONS: The use of MCS devices for acute
      catastrophic situation appears warranted despite the abbreviated transplant
      evaluations. It is important for improving the outcomes with beginning MCS
      support before multiple organ system failure occurs, and accurately identifying
      individuals who can benefit from MCS.

PMID- 19094535
TI  - [Preliminary experiences of application of sentinel lymph node navigation
      technique in early gastric cancer].
AB  - OBJECTIVE: To investigate the feasibility and clinical significance of sentinel
      lymph node (SLN) navigation limited surgery in early gastric cancer (EGC).
      METHODS: Thirty-nine patients confirmed with EGC between January 2002 and
      December 2006 were randomly divided into tailored surgery group (20 cases) and
      conventional surgery group (19 cases). By combining the mapping agents of (99m)Tc
      labeled sulfur colloid solution and blue violet, SLN biopsy was conducted in
      tailored surgery group, in which a limited gastric resection with D0-D1
      lymphadenectomy was performed in 17 cases with negative SLN examined by routine
      HE staining during operation; standard radical gastrectomy with lymphadenectomy
      (D2) was conducted in the other 3 cases with positive SLN and in all the cases of
      conventional surgery group. The diagnostic accuracy and false-negative rate of
      SLN status were calculated respectively. The operation outcome and postoperative
      complication and survival rate were compared between the two groups. RESULTS:
      SLNs were detected in all 20 patients with a successful detection rate of 100% in
      tailored surgery group. The number of detected SLNs ranged from 1 to 3, with a
      mean of 2.2 per case. The diagnostic accuracy and false-negative rate was 95% and
      5%, respectively. The hospital stay and recovery time of gastrointestinal
      functions in patients undergoing limited surgery were significantly shorter than
      in conventional surgery group and with similar postoperative survival and less
      complications. CONCLUSIONS: SLN biopsy may provide an accurate diagnostic
      procedure for detecting lymph node metastasis in EGC. Patients with node-negative
      EGC receiving limited surgery are likely to benefit from minimally invasive
      approach with the similar survival as standard radical surgery.

PMID- 19094536
TI  - [The clinical anatomical research of the tibial attachment of the posterior
      cruciate ligament and the tibial tunnel position in double-bundle posterior
      cruciate ligament reconstruction].
AB  - OBJECTIVES: To provide the data on the shape, sizes, and locations of the
      attachments of the anterolateral bundle (ALB) and posteromedial bundle (PMB) of
      the posterior cruciate ligament (PCL) to the tibia, and to determine the
      reference landmarks and the methods for tibial tunnel positioning in double
      bundle PCL reconstruction using double-double tunnel. METHODS: Thirty cadaveric
      knees were used as specimens. PCLs were separated into bundles according to the
      PCL tension pattern during knee flexion-extension, and the functional bundle in
      each bundle was determined. Data were obtained to describe the size, shape,
      position, and center of the attachments of PCL bundles. The reference landmarks
      and methods for tibial tunnels positioning in double-bundle PCL reconstruction
      using double-double tunnel were determined. RESULTS: The PCL insertion site was
      situated in the posterior intercondylar fossa. The longitudinal axis of the
      tibial attachment of PCL proceeded from proximal medial to distal lateral, and
      the mean angle between them and the tibial shaft was (16.5 +/- 1.4) degrees . The
      tibial insertion site of ALB and PMB were arranged in the proximal and distal on
      the whole, the tibial attachment of ALB could generally be described as rhomb in
      shape, and the mean area of it was (90 +/- 20) mm(2); the tibial attachment of
      PMB was rectangle in shape, the mean area of it was (96 +/- 32) mm(2), there was
      no statistic difference between the area of them (P > 0.05). There were
      functional bundles in both ALB and PMB persistently, which attached to the distal
      lateral portion of the tibial attachment of ALB and the distal-medial portion of
      the tibial attachment of PMB respectively, they were both oval in shape, the mean
      area of them were (35 +/- 12) mm(2) and (36 +/- 6) mm(2) respectively, the
      difference between them was no statistic significant (P > 0.05). The mean
      distance between the centres of the tibial attachments of the functional bundles
      of ALB and that of PMB was (12.7 +/- 1.9) mm. The medial tibial spine, lateral
      tibial spine and the bony ridge on the posterior-proximal tibia were the key
      anatomic landmarks that could be used to aid in placement of independent tibial
      tunnels for a 2-bundle PCL reconstruction. CONCLUSIONS: The tibial attachment of
      the PCL is sufficiently large to allow for placement of 2 independent tunnels.
      There are functional bundles in both ALB and PMB persistently and the optimum
      position for the tibial tunnel in double-bundle PCL reconstruction using double
      double tunnel should be located in the attachment sites of the functional bundles
      of ALB and PMB.

PMID- 19094537
TI  - [A cadaveric study of relationships among rotational alignment reference axes of
      distal femur and tibial mechanical axis].
AB  - OBJECTIVES: To investigate the relationships among rotational alignment reference
      axes of distal femur and tibial mechanical axis, and determine the safest
      rotational alignment reference axis. METHODS: Digital photos were taken of 30
      cadaveric lower extremities with knee in extension and flexion at 90 degrees ,
      angles were measured among tibial mechanical axis and a line perpendicular to
      clinical epicondylar axis, a line perpendicular to surgical epicondylar axis,
      Whiteside's line and femoral mechanical axis. Statistical analysis of
      relationships among those axes were performed. RESULTS: The angles among the
      tibial mechanical axis and a line perpendicular to the clinical epicondylar axis,
      a line perpendicular to the surgical epicondylar axis, Whiteside's line and
      femoral mechanical axis were 0.6 degrees varus, 3.9 degrees varus, 0.2 degrees
      valgus and 3.0 degrees varus respectively. The angle between the femoral
      mechanical axis and the tibial mechanical axis was significantly larger than the
      angles among the tibial mechanical axis and a line perpendicular to the clinical
      epicondylar axis, the Whiteside's line (P < 0.05). There was no significant
      difference compared with the angle between a line perpendicular to the surgical
      epicondylar axis and the tibial mechanical axis. Angles of the clinical
      epicondylar axis, the surgical epicondylar axis and the Whiteside's line between
      knee extension and flexion were 2.3 degrees valgus, 0.9 degrees varus and 3.1
      degrees valgus respectively. CONCLUSION: The surgical epicondylar axis rather
      than the clinical epicondylar axis or the Whiteside's line is the safest femoral
      rotational alignment reference axis intraoperatively.

PMID- 19094538
TI  - [The effects of continuous passive motion on tendon-bone healing of the tendon
      autograft used for anterior cruciate ligament reconstruction in a rabbit model].
AB  - OBJECTIVE: To study the effects of continuous passive motion on the tendon-bone
      healing of the semi-tendinous tendon autograft used for anterior cruciate
      ligament (ACL) reconstruction in rabbits. METHODS: In 12 healthy 8-month-old male
      rabbits, an ACL reconstruction was performed by using double semi-tendinous
      tendon autograft. Postoperatively these animals were treated by either continuous
      passive motion (CPM) or cage activity. Specimens of the grafts were collected at
      6, 12, 24 weeks postoperatively. Histological change in the tendon-bone healing
      was studied by haematoxylin-eosin and toluidine blue. RESULTS: There was more new
      fiber tissue in the anterior half of the interface. Osteoclasts were most
      numerous at the tunnel aperture and in the anterior half of the interface.
      Cartilage in the tendon-bone interface was localized to the posterior aspect of
      tunnels, the area where compressive stress would be predicted. CPM group
      developed a denser connective tissue with less vascularity and cellularity. The
      bone tunnel had more areas with ingrowing denser connective tissue compared with
      cage activity specimens. With the growth of Sharpery's fibers and fibrocartilage
      into the interface, a direct ligament insertion was found. In the CPM specimens,
      the interface tissue was more mature and the direct insertion was broader and
      more structured. CONCLUSIONS: Compressive stress promotes chondroid formation,
      and the tension promotes fiber formation. Tendon-bone healing may be optimized by
      CPM after tendon transplantation into a bone tunnel.

PMID- 19094539
TI  - [Research of signaling pathway of vascular endothelial growth factor regulating
      by hepatitis B virus X protein].
AB  - OBJECTIVE: To study the function of nuclear factor-kappaB (NF-kappaB) signaling
      pathway in regulating vascular endothelial growth factor (VEGF) by hepatitis B
      virus X protein (HBx). METHODS: After the establishment of L02-HBx cell line with
      stable transfected HBx gene, NF-kappaB signaling pathway blocker PDTC was
      introduced to cut off its signal transduction. Double immunofluorescent staining
      and laser scanning confocal microscopy were applied to study the activation and
      deactivation of NF-kappaB signaling pathway. Real-time PCR and Western blot were
      used to observe the expression of VEGF gene before and after the HBx
      transfection, as well as the treatment with PDTC. RESULTS: The NF-kappaB
      signaling pathway of L02-HBx cells was activated after transfection with HBx gene
      as compared to the control L02 cells without treatment. The mRNA and protein
      levels of VEGF in L02-HBx cells increased 4.07 +/- 0.31 and 4.34 +/- 0.64 times
      respectively. The difference was of statistical significance (P < 0.05) in
      comparison with the control cells. The mRNA levels of VEGF decreased to 2.33 +/-
      0.22 and 1.86 +/- 0.18(P < 0.05) and at the same time the expression of VEGF also
      reduced to 2.52 +/- 0.29 and 2.17 +/- 0.34 (P < 0.05), after treatment with 25.0
      micromol/L and 50.0 micromol/L PDTC for 24 h respectively when the NF-kappaB
      signaling pathway was blocked. There was no significant difference in VEGF mRNA
      and protein levels when treated with 12.5 micromol/L PDTC for 24 h. CONCLUSION:
      NF-kappaB signaling pathway maybe one of the routes through which HBx up-regulate
      the expression of VEGF to promote angiogenesis in hepatocellular carcinoma.

PMID- 19094540
TI  - [Study on three dimensional reconstruction and simulation surgery of spleen].
AB  - OBJECTIVE: To study the three-dimensional (3D) reconstruction and the
      visualization simulation surgery of spleen based on the scanning data of 64-slice
      helical computed tomograph (CT). METHODS: The original data of 64-slice helical
      CT of spleen was collected, and then the CT image sequences were segmented and
      automatically extracted using auto-adapted region growth algorithm, and were
      conducted with the segmented images by adopt self-developed image processing
      software for 3D reconstruction. Finally, the 3D models were imported into
      FreeForm Modeling System for modifying and smooth. And the visualization
      simulation surgery was performed before splenectomy. RESULTS: It was fast and
      effective to utilize auto-adapted region growth algorithm to conduct spleen image
      program segmentation; the reconstructed models were seen clearly and could
      reappear the structure of the spleen and the important surrounding organs. The
      effect of the splenectomy simulation surgery was similar to the practical
      surgery. CONCLUSIONS: The research on 3D models of spleen and visualization
      simulation surgery of splenectomy could lead to clinical benefits. It maybe
      improve the surgical effect and decrease the surgical risk and reduce the
      complication demonstrating visualized operation before surgery.

PMID- 19094553
TI  - [Developmental dislocation or dysplasia of hip: diagnosing early and performing
      the operation correctly according to the classification].

PMID- 19094554
TI  - [The problems and strategies in the diagnosis and treatment of developmental
      dysplasia of hip].

PMID- 19094555
TI  - [A comparative study of the role of two femoral shortening techniques in total
      hip arthroplasty on patients with Crowe's IV congenital dislocated hips].
AB  - OBJECTIVE: To compare proximal femoral resection with transverse subtrochanteric
      osteotomy in the treatment of Crowe's IV congenital dislocated hip (CDH) with
      total hip arthroplasty (THA). METHODS: Thirty-six primary hip arthroplasties were
      performed in patients with Crowe grade IV CDH from April 2003 to October 2007.
      These patients were divided into two groups, one for proximal femoral resection
      (n = 20) and another for subtrochanteric osteotomy (n = 16). The leg length
      discrepancy, rotation center height and Harris score were measured pre- and post
      operation to compare the two methods of osteotomy. RESULTS: All surgeries were
      successfully performed. The average leg discrepancy was 0.6 cm (range from 0 to
      1.5 cm) for subtrochanteric osteotomy group and 0.3 cm (range from -1.0 to 1.5
      cm) for proximal femoral resection group, there was no significant difference
      between them (P > 0.05). There were also no statistically significant difference
      between the two groups in other index. The complication rates were much higher in
      the proximal femoral resection group. At the latest follow up, the Harris score
      of subtrochanteric osteotomy group was 90 +/- 6, and the proximal femoral
      resection group was 83 +/- 8. There was statistical difference between the two
      groups (P < 0.05). CONCLUSIONS: Although both the femoral shortening techniques
      can restore the leg length of Crowe IV CDH, the subtrochanteric osteotomy
      technique has advantage of avoiding the potential complications in the high
      riding patients (high dislocation > 4 cm).

PMID- 19094556
TI  - [Hip resurfacing arthroplasty for secondary osteoarthritis after developmental
      dysplasia of hip].
AB  - OBJECTIVE: To study the clinical results of metal on metal hip resurfacing
      arthroplasty for developmental dysplasia patients. METHODS: From March 2005 to
      December 2006, 34 cases of developmental dysplasia patients (Crowe I, Crowe II)
      were attempted to have metal on metal hip resurfacing arthroplasty. There were 29
      females (32 hips), 5 males (5 hips). The average age was 45 (26 - 57) years old.
      Radiographic and clinical evaluations were taken at 6 weeks, 3 months, 1 year and
      then once a year postoperatively. The average Harris score was 35 (25 - 44). Hip
      flexion was 101 degrees , abduction 24 degrees , adduction 15 degrees . RESULTS:
      Three patients were turned to total hip arthroplasty during operations. Thirty
      one patients (34 hips) received hip resurfacing surgery. These 31 patients were
      followed for average 21.4 months (12 - 33 months). The average Harris score was
      94 (82 - 100) at the latest follow-up, and there was statistical difference
      compared with the preoperative score (P < 0.01). Hip flexion increased to 133
      degrees , abduction to 48 degrees , adduction to 26 degrees . No radiolucency
      line was found at both acetabular and femoral sides in all the patients. The
      average abduction angle of acetabular cup was 43 degrees (40 degrees - 53 degrees
      ), and the average stem shaft angle was 139 degrees (130 degrees - 145 degrees ).
      CONCLUSIONS: The short term result is excellent. While the mid to long term
      results for hip resurfacing arthroplasty in developmental dysplasia patients are
      still looking forward, and the meticulous surgical technique and strict patient
      selection are the key of the good results.

PMID- 19094557
TI  - [Effect of total hip replacement on lumbago in unilateral developmental hip
      dysplasia].
AB  - OBJECTIVE: To assess the effect of total hip replacement on lumbago in patients
      with unilaterally developmental hip dysplasia. METHODS: From January 2001 to
      January 2006, 39 adult patients with unilateral developmental hip dysplasia co
      exiting lumbago were included. Among them, there were 32 females and 7 males, age
      from 38 years to 73 years. According to Crowe classification system, there were 4
      in type I, 20 in type II,8 in type III and 7 in type IV. They were performed
      total hip replacement. The Harris Hip Score and the Oswestry Disability Index
      were used to evaluate hip and spine symptoms in same patient before and 3, 24
      months after operation. RESULTS: Thirty-nine patients were evaluated, both hip
      and spinal pain and function were significant improved. The mean Harris score
      increased from 44 to 84 (P < 0.01). The mean Oswestry Scores dropped from 36 to
      25 (P < 0.01). CONCLUSION: Spinal function and lumbago is improved after total
      hip replacement in patients with unilateral developmental hip dysplasia at 3
      months, which is maintained and enhanced in 2 years.

PMID- 19094558
TI  - [Soft tissue balancing in the total hip arthroplasty for severe developmental
      dysplasia of the hip in adults].
AB  - OBJECTIVE: To assess clinical result of soft tissue balancing in primary total
      hip arthroplasty for severe developmental dysplasia of the hip in adults.
      METHODS: From December 2000 to August 2006, 26 primary cementless total hip
      arthroplasties combined with soft tissue balancing were performed in 21 cases for
      the treatment of severe developmental dysplasia of the hip. Patients were
      classified as type III (20 hips) and type IV (6 hips) according to Crowe
      classification. All acetabular cups were placed in their original anatomic
      location by soft tissue releasing and subtrochanteric shortening osteotomy.
      Thereafter, postoperative clinical and radiological results were evaluated.
      RESULTS: The mean length of follow-up was 4.8 years (range, 13 months-7 years).
      Limp improved by at least one grade in 62% of the cases. Leg-length discrepancy
      was corrected significantly and osteotomy was undertaken in 13 hips with a mean
      decrease length of 0.9 cm by effective releasing. Harris scores improved
      significantly from a mean of 41.2 preoperatively to 89.6 postoperatively. No
      dislocations, infections and prosthesis loosening were found at the final follow
      up evaluation. CONCLUSION: Soft tissue balancing in total hip arthroplasty can
      facilitate acetabular reconstruction to normalize the hip center in severe
      developmental dysplasia of the hip, as a result, satisfactory short-term result
      can be obtained by restoring normal function and anatomic structure.

PMID- 19094559
TI  - [Reconstruction of the acetabular in the Crowe III dysplastic hip].
AB  - OBJECTIVE: To investigate the method and the outcome of the acetabular
      reconstruction in the Crowe III dysplastic hip. METHODS: From January 2001 to
      June 2007, 43 cases (54 hips) were diagnosed osteoarthritis secondary to Crowe
      III dysplastic hip. Total hip arthroplasty was performed in all cases. The Harris
      score was 39 pre-operation. The method of the acetabular reconstruction included
      acetabular deepening (group A), medial-wall osteotomy (group B), femoral head
      bone grafting (group C). Radiography data and Harris score were taken to evaluate
      the clinical outcome. RESULTS: The method of the acetabular reconstruction
      included acetabular deepening in 27 cases (34 hips), medial-wall osteotomy in 12
      cases (15 hips), femoral head bone grafting in 4 cases (5 hips). Forty cases were
      followed up by the mean time of 29 months. The bone union time of the osteotomy
      and bone grafting were 4 - 5 months postoperation. In the three groups the
      obliquity angle of the cup were (41.0 +/- 7.5) degrees , (46.0 +/- 7.7) degrees ,
      (39.0 +/- 11.0) degrees ; the anteversion angle of the cup were (10.0 +/- 2.8)
      degrees , (9.0 +/- 2.5) degrees , (4.0 +/- 1.9) degrees ; the rotation center of
      the hip was shift superiorly (8.4 +/- 3.6) mm, (7.3 +/- 2.6) mm, (1.2 +/- 0.5)
      mm; the rotation center of the hip were shift internally (7.0 +/- 1.5) mm, (9.9
      +/- 1.7) mm, (-2.7 +/- 1.2) mm, and the Harris score were 89, 91, 86 at the
      follow up. The complication included deep venous thrombosis in 2 cases, pulmonary
      embolism in 2 cases, sciatic nerve palsy in 4 cases. CONCLUSION: Acetabular
      deepening, medial-wall osteotomy, femoral head bone grafting can be used in
      reconstruction of the acetabular in the Crowe III dysplastic hip.

PMID- 19094562
TI  - [Liver resection: single center experiences of 2008 consecutive resections in 20
      years].
AB  - OBJECTIVE: To analyze operative and perioperative factors associated with
      hepatectomy. METHODS: 2008 consecutive patients undergoing hepatectomy from
      January 1986 to December 2005 at Chinese People's Liberation Army General
      Hospital were investigated retrospectively according to their medical
      documentation. Diagnoses were made on basis of pathological results. RESULTS:
      Malignant and benign liver diseases accounted for 58.5% and 41.2%, respectively.
      In the former, primary liver cancer accounted for 76.1% and hilar
      cholangiocarcinoma for 6.7%. Hemangioma (41.7%) and hepatolithiasis (29.6%) were
      listed in the first two in the latter group with relatively more patient ratios.
      Isolated caudate lobe resection was performed in 25 patients and micro-wave
      inline coagulation was induced in 236 cases of liver resection. In all cases,
      those with blood loss less than 200 ml accounted for 50.5% (1015/2008), whereas
      those with more than 400 ml accounted for 28.4% (570/2008). In patients performed
      micro-wave inline coagulation liver resection, those with blood loss less than
      200 ml and more than 400 ml accounted for 60.6% (143/236) and 19.9% (47/236),
      respectively, which differed significantly from the average level (P < 0.05). The
      postoperative complication incidence was 14.44% for all cases, 12.54% for primary
      liver cancer, 16.40% for secondary liver cancer, and 16.32% for hepatolithiasis.
      Complication incidence of primary liver cancer with tumor size smaller than 5 cm
      was 11.65% and that with tumor larger than 10 cm was 14.69%. There was no
      significant difference between the two groups. All-case hospital mortality was
      0.55% and that for liver malignant disease was 0.60%, hilar cholangiocarcinoma
      2.53%. CONCLUSION: Hepatectomy can be performed safely with low mortality and low
      complication incidence, provided that it is carried out with optimized
      perioperative management and innovative surgical technique.

PMID- 19094563
TI  - [Experiences on surgical treatment of severe aortic valve stenosis: a report of
      171 cases].
AB  - OBJECTIVE: To analyze the experiences on surgical treatment of severe aortic
      valve stenosis. METHODS: From December 1990 to December 2006, 171 patients with
      severe aortic valve stenosis underwent aortic valve replacement (AVR). There were
      135 males and 36 females aged from 10 to 75 years old, with a mean of (45.8 +/-
      15.6) years old. The intervals between the first episode of exertion dyspnea and
      administration to operation were 2 months to 52 years. The pathological lesions
      of the group were rheumatic aortic valve stenosis in 75 cases, calcified aortic
      stenosis in 66 cases, bicuspid aortic valve in 26 cases and other congenital
      aortic valve stenosis in 4 cases. One hundred and twenty-four patients underwent
      AVR, 7 AVR combined with replacement of the ascending aorta, 5 AVR with coronary
      artery bypass grafting, 19 AVR with mitral valve plasty (MVP), 8 AVR with plasty
      of the ascending aorta and 8 AVR with enlargement of the aortic root. RESULTS:
      The averaged operation time was (4.4 +/- 0.6) h. Cardiopulmonary bypass (CPB)
      time was (124.7 +/- 38.5) min and the aorta clamp time was (78.3 +/- 21.7) min.
      The averaged blood loss during operation was (754.5 +/- 518.4) ml. All the
      procedures were successfully performed and all patients were weaned off CPB
      uneventfully. The indication of early complications was 12.3% (21/171), including
      low cardiac output syndrome in 7 cases, multi-organ failure in 3 cases,
      endocarditis in 1 case, renal dysfunction in 4 cases, ventricular fibrillation in
      1 case, excessive bleeding in 2 cases, III atrial-ventricular block in 2 cases,
      and mediastinal infection in 1 case. The total mortality was 5.8% (10/171) with
      the main causes as cardiac failure for 4 cases, arrhythmia for 1 case, multi
      organ failure for 4 cases, and infectious endocarditis for 1 case. CONCLUSIONS:
      Successful management of severe aortic valve stenosis requires sophisticated
      surgical techniques and experienced peri-operative care. Satisfactory results can
      be achieved if valve replace surgery is performed adequately.

PMID- 19094564
TI  - [The relationship between endothelin receptors and chronic venous insufficiency
      of lower extremities].
AB  - OBJECTIVE: To investigate the effect of endothelin receptors in chronic venous
      insufficiency (CVI) in lower extremities. METHODS: Ten cases of varicose veins
      from CVI patients (as case group) and ten cases of non-varicose veins (as control
      group) were investigated in this study. The two groups were divided into two
      groups respectively: endothelium-intact group and de-endothelium groups. The
      vasoconstriction mediated by endothelin A (ETA) and endothelin B (ETB) receptors
      was recorded with myography. The distribution of ETA and ETB receptors was
      detected by immunohistochemistry method. RESULTS: Endothelin-1 (ET-1) and
      sarafotoxin 6c (S6c) induced concentration-dependent contraction in the veins. In
      endothelium-intact veins, the E(max) and pD(2) of contraction curve induced by ET
      1 were 132.30% +/- 43.42% and 6.03 +/- 0.35, respectively in control group;and
      were 19.24% +/- 12.94% and 6.78 +/- 0.46, respectively in case group. The E(max)
      and pD(2) in case group were much lower than in control group (P < 0.05). The
      E(max) and pD(2) induced by S6c were 30.10% +/- 12.90% and 6.54 +/- 0.36,
      respectively in control group, and were 9.61% +/- 1.32% and 6.75 +/- 0.29,
      respectively in case group; The E(max) in case group was lower than in control
      group (P < 0.05). In de-endothelium veins, E(max) and pD(2) of S6c were 146.18%
      +/- 32.33% and 6.50 +/- 0.17 in control group, and 32.93% +/- 3.00% and 6.69 +/-
      0.39 in case group; The E(max) in case group was significantly lower than in
      control group (P < 0.05). ETA receptors was located in endothelium mainly, and
      ETB receptors in smooth muscle cells mainly. The sites of both ETA and ETB
      receptors were decreased in case group obviously. CONCLUSIONS: The contraction
      mediated by ETA receptor and ETB receptor was decreased with a decrease of ETA
      receptor and ETB receptor sites in varicose veins of CVI. The contraction
      insufficiency and down-expression of ETA receptor and ETB receptor are correlated
      with CVI.

PMID- 19094565
TI  - [Using tension-band laminoplasty as a management for cervical ossification of
      posterior longitudinal ligament].
AB  - OBJECTIVE: To evaluate the effectiveness of Tension-band Laminoplasty (TBL) as a
      management for cervical ossification of posterior longitudinal ligament (OPLL).
      METHODS: Forty-six patients with cervical OPLL and undergone TBL in our
      department were chosen for the present study, including 33 male and 13 female.
      The mean age was 59 years (36 - 77 years). These OPLLs were confirmed as
      following types: 4 cases of single spinal level, 20 cases of continuous and 22
      cases of mixed type. C(3) or/and C(2) levels were involved in 16 cases. All the
      patients underwent C(2 - 7) TBL, to which C(1) laminectomy was added for the
      cases with C(3) and/or C(2) involved. The neurological effect was evaluated by
      using Japanese Orthopedic Association (JOA) scoring criteria for cervical
      myelopathy. The anatomical effect was analyzed by comparing the pre- and post
      operatively roentgenograms and MRIs. Wilcoxon's rank test was used for the
      statistics study. RESULTS: For 42 (91.3%) patients, the JOA scores were improved
      for approximately 2 points after the operation, posterior shift of the spinal
      cord was obtained, while the diameters of dural sleeves and spinal cords were
      enlarged, yet the spinal alignments were not significantly interrupted.
      CONCLUSIONS: TBL was proved an effective treatment for cervical OPLL and it could
      be expanded to include C(1) laminectomy if the spinal levels upper than C(4) were
      involved.

PMID- 19094566
TI  - [Surgical treatment and prognosis in patients with squamous cell carcinoma of
      thoracic esophagus].
AB  - OBJECTIVE: To analyze the prognostic factors of thoracic esophageal squamous cell
      carcinoma (ESCC) after esophagectomy. METHODS: The clinicopathologic data of 716
      patients with thoracic ESCC from January 1990 to December 1998 were analyzed
      retrospectively. There were 538 male and 178 female patients aged from 24 to 78
      years old with a median of 57 years old. Cumulative survival rate was analyzed by
      the Kaplan-Meier method and compared by the Log-rank test. COX regression model
      was used for multivariate prognostic analysis. RESULTS: The overall 1-, 3-, 5-
      and 10-year survival rates were 82.9%, 44.3%, 34.2% and 25.7% respectively. The 5
      year survival rates was 80.0%, 51.2%, 19.7% and 13.3% for stage I, stage IIA,
      stage IIB and stage III respectively. Of the 716 patients, 151 (21.1%) patients
      recurred, including 48 (84.2%) of stage IIA recurrence, 22 (91.7%) of stage IIB
      recurrence and 63 (90.0%) of stage III recurrence occurred within 3 years
      postoperatively. Univariate analysis revealed that the factors impacting the
      prognosis were gender, depth of invasion, lymph node metastasis, pathologic
      stage, number of lymph node metastatic field, differentiation, surgical margin
      and tumor relapse. Multivariate analysis showed that depth of invasion, lymph
      node metastasis, pathologic stage and tumor relapse were independently associated
      to poor prognosis. CONCLUSIONS: Depth of invasion, lymph node metastasis,
      pathologic stage and tumor relapse are the independent factors of ESCC. Surgery
      is still the primary treatment for stage I-IIA esophageal cancer; but it is
      suggested to adopt surgical treatment as primary modality combined with other
      therapies for stage IIB-III esophageal cancer.

PMID- 19094567
TI  - [Loss of heterozygosity analysis of microsatellites on multiple chromosome
      regions in dysplasia and squamous cell carcinoma of esophagus].
AB  - OBJECTIVE: To investigate the molecular alterations related to the carcinogenesis
      of esophageal squamous cell carcinoma (SCC), and also to find some molecular
      markers for the early detection of this cancer. METHODS: The resected tumor
      specimens and dysplasia tissues from 34 patients with esophageal cancer as well
      as their matched blood DNAs were analyzed for loss of heterozygosity (LOH) at 16
      microsatellites by using PCR and fluorescence-based DNA sequencing technology.
      Mild and moderate dysplasia was classified as light-grade dysplasia (LGD), and
      severe dysplasia as high-grade dysplasia (HGD). The frequencies of LOH at 16
      microsatellites were compared between tissue specimens with different
      histological diagnosis. RESULTS: The total frequency of LOH for 16
      microsatellites increased significantly in more severe lesions. There was
      significant difference in the frequency of LOH among LGD and HGD as well as SCC.
      A total of eight loci (D3S1597, D3S2452, D3S1285, D4S174, D5S2501, D9S125,
      D13S153 and D17S786) presented LOH in LGD samples. A reversion from LOH to retain
      of heterozygosity was observed at loci D3S2452, D4S174, D9S125 and D17S261
      respectively when compared HGD with SCC samples obtained from 4 patients.
      CONCLUSIONS: An accumulation of molecular alterations would be needed during the
      carcinogenesis of esophageal cancer. LOH analysis at some specific loci would be
      helpful for the early detection of esophageal cancer. The genetic heterogeneity
      possibly exists in the tumorigenesis of esophageal cancer.

PMID- 19094577
TI  - [Pathologic diagnosis of serous borderline tumors of the ovary].

PMID- 19094578
TI  - [Practice of cervical cytology in China and overseas].

PMID- 19094579
TI  - [Study on expression of estrogen receptor isoforms in eutopic and ectopic
      endometrium of ovarian endometriosis].
AB  - OBJECTIVE: To investigate the distribution of ER isoforms in endometriosis and
      eutopic endometrium. METHODS: Tissue samples of patients with ovarian
      endometriosis, treated in People's Liberation Army General Hospital from January
      2004 to December 2006, were retrieved. A total of 60 cases of ovarian
      endometriotic cysts with their corresponding eutopic endometrium (30 cases of
      proliferation phase and 30 of secretary phase eutopic endometrium) and 30 cases
      of normal endometrium (15 proliferative and 15 secretary phase endometrial
      samples respectively) were included. Expressions of ERalpha and ERbeta were
      analyzed using immunohistochemistry and the expression ratio was statistically
      analyzed by using SPSS 12.0 software. RESULTS: Expressions of both ERalpha and
      ERbeta in epithelial cells were positively correlated with that of the stromal
      cells. The expression of ERalpha in eutopic endometrium (73.3% in epithelium and
      76.7% in stroma) was significantly higher than that in ovarian endometriotic
      cysts (43.3% in epithelium and 46.7% in stroma), or normal control (56.7% in
      epithelium and 50.0% in stroma, respectively, each P < 0.05. However, the
      expression of ERbeta (90.0% in epithelium and 76.7% in stroma) was higher in
      ovarian endometriotic cysts than that in the eutopic endometrium (68.0% in
      epithelium and 63.3% in stroma respectively, P < 0.05), and ERbeta expression in
      eutopic endometrium was higher than that in the normal control endometrium (36.7%
      in epithelium and 26.7% in stroma, respectively, P < 0.05). The expressions of
      both ERalpha and ERbeta changed periodically in eutopic and normal endometrium,
      whereas ERalpha and ERbeta level were less variable in the ectopic endometrium.
      The expression of ERbeta was statistically higher than that of ERalpha (P < 0.05)
      in ectopic endometrium, whereas no significant difference was seen between the
      two isoforms in the eutopic or normal endometrium. CONCLUSIONS: Both ERalpha and
      ERbeta have higher expression levels in eutopic endometrium of patients with
      ovarian endometriotic cysts. ERbeta is predominantly expressed in endometriotic
      cysts, where the expression of ERalpha is limited. The different distribution of
      ERalpha and ERbeta may play an important role in the development of ovarian
      endometriosis.

PMID- 19094580
TI  - [Expression of Skp2 in cervical squamous cell carcinoma and precancerous lesions
      and its correlation with HPV16/18 infection].
AB  - OBJECTIVE: To study the expression of Skp2 in cervical squamous cell carcinoma
      (SCC) and its precancerous lesions, and to investigate its relationship with
      human papillomavirus (HPV) infection. METHODS: The expression of Skp2 protein and
      HPV16/18 DNA was determined using immunohistochemistry and in-situ hybridization
      in 30 cases of normal cervical squamous epithelium, 29 cases of low-grade
      intraepithelial neoplasia, 31 cases of high-grade intraepithelial neoplasia and
      31 cases of cervical SCC. RESULTS: Skp2 expression was not detected in normal
      cervical squamous epithelium and no significant difference was obtained
      statistically on Skp2 expression between normal cervical squamous epithelium and
      low-grade intraepithelial neoplasia (P > 0.05). However, the expression of Skp2
      gradually increased with elevation of epithelial lesion grading in an order from
      low to high grade and to cervical SCC (P < 0.01). The positive rate of HPV16/18
      DNA in cases of normal cervical squamous epithelium, low-grade, high-grade
      intraepithelial neoplasia and cervical SCC was significantly different (P <
      0.01), although both high-grade intraepithelial neoplasia and cervical SCC had a
      similar high HPV infection rate up to 96.8%. There was no correlation obtained
      between Skp2 expression and HPV16/18 infection in low-grade intraepithelial
      neoplasia. In contrast, expression of Skp2 and HPV infection were significantly
      correlated in both high-grade intraepithelial neoplasia and cervical SCC (gammaH
      = 0.373, gammaC = 0.416, P < 0.05). CONCLUSIONS: Abnormal expression of Skp2 is
      present mainly in high-grade cervical intraepithelial neoplasia and invasive
      carcinoma, which may be considered as a surrogate marker for the high-grade
      lesions. Skp2 may play a key role in the development of cervical squamous
      carcinoma induced by HPV16/18 infection, through E7-Skp2-Rb signaling pathway.

PMID- 19094581
TI  - [Primary diffuse large B-cell lymphoma of the appendix: report of a case].

PMID- 19094582
TI  - [HER2 status in breast cancer of Chinese women: a study of 1170 cases using
      fluorescence in-situ hybridization].
AB  - OBJECTIVE: To assess the prevalence of HER2 amplification according to HER2 and
      chromosome 17 copy numbers and HER2 FISH (fluorescence in-situ hybridization)
      ratio in breast cancer occurring in Chinese women. METHODS: Eleven hundreds and
      seventy cases of breast cancer occurring in Chinese women, who would be treated
      by trastuzumab and/or relevant chemotherapy based on HER2 status, were enrolled
      into the study. The formalin-fixed and paraffin-embedded tumor tissues were
      tested by FISH (PathVysion, Vysis). RESULTS: Among the 1170 cases of breast
      cancer studied, 408 cases (34.87%) were FISH-negative, whereas 762 cases (65.13%)
      were FISH-positive, including 87 cases (87/762, 11.42%) with highly amplified
      HER2 gene (signals arranged in aggregates). As for the remaining 675 FISH
      positive cases, 159 cases (23.56%) showed low amplification (HER2/CEP17 ratio = 2
      to 4), 422 cases (62.52%) showed moderate amplification (ratio = 4 to 10) and 94
      cases (13.93%) showed high amplification (ratio > 10) for HER2 gene. Only 14 of
      the 1170 cases (1.20%) had indeterminate results (ratio between 1.8 and 2.2),
      including 1.23% (5/408) borderline FISH-negative (ratio between 1.8 and 2.0) and
      1.18% (9/762) borderline FISH-positive (ratio between 2.0 and 2.2). Our data
      showed that 73.00% (854/1170) of cases were chromosome 17 aneusomy, including
      22.65% (265/1170) hypodisomy (chromosome 17 copy number per cell < or = 1.75),
      38.38% (449/1170) low polysomy (chromosome 17 copy number per cell 2.26 to 3.75)
      and 11.97% (140/1170) high polysomy (chromosome 17 copy number per cell > or =
      3.76). The frequency of chromosome 17 polysomy was 50.34%. In the FISH-positive
      subgroup, 23.88% (182/762) was disomy (chromosome 17 copy number per cell between
      1.76 and 2.25), 24.15% (184/762) hypodisomy, 39.37% (300/762) low polysomy and
      12.60% (96/762) high polysomy. The frequency of chromosome 17 polysomy in the
      FISH-positive subgroup was 51.97%. In the FISH-negative subgroup, 32.84%
      (134/408) were disomy, 19.85% (81/408) hypodisomy, 36.52% (149/408) low polysomy
      and 10.78% (44/408) high polysomy. The frequency of chromosome 17 polysomy in the
      FISH-negative subgroup was 47.30%. On the other hand, HER2 monoallelic deletion
      (HER2/CEP17 < or = 0.7) was observed in 2.39% of cases. Chromosome 17 monosomy
      was detected in 5.00% (38/762) and 4.41% (18/408) of HER2-positive and HER2
      negative groups, respectively. A HER2 ratio of < 1.5 was noted in 32.30% of all
      cases (including 92.65% of HER2-negative cases), compared with 9.23% (108/1170)
      with ratio between 1.5 and 2.2. CONCLUSIONS: The results show that a high
      amplification of HER2 gene is detected by FISH. Moderate amplification of HER2
      gene and chromosome 17 polysomy are commonly seen in breast cancer patients in
      China Mainland. These findings may carry significant clinical and pathogenetic
      implication.

PMID- 19094583
TI  - [Significance of interleukin-1beta expression and microvascular density in
      invasive micropapillary carcinoma of breast].
AB  - OBJECTIVE: To study the significance of interleukin-1beta (IL-1beta) expression
      and microvascular density (MVD) in invasive micropapillary carcinoma (IMPC) of
      breast. METHODS: Immunohistochemical study for IL-1beta and CD34 was performed on
      100 cases of IMPC and 97 cases of invasive ductal carcinoma (IDC). The
      relationship between IL-1beta expression, MVD and various pathologic parameters
      (estrogen and progesterone receptor status, Ki-67 proliferative index, histologic
      grade and lymph node metastasis) in IMPC was analyzed. RESULTS: There was no
      significant difference in expression of IL-1beta between IMPC and IDC (P =
      0.924). The expression of IL-1beta positively correlated with proliferative index
      (P = 0.023), histologic grade (P = 0.038) and lymph node metastasis (P = 0.008),
      and negatively correlated with estrogen receptor expression (P = 0.035). The MVD
      in IMPC was significantly higher than that in IDC (66.4 versus 60.0, P = 0.003).
      The mean MVD in node-positive IMPC was higher than that in node-negative IMPC
      (68.8 versus 54.4, P = 0.001). In IMPC, the MVD in histologic grade II and III
      tumors was much higher than that in histologic grade I tumors (68.3 versus 59.9,
      P = 0.025). It had no relationship with hormonal receptor status and
      proliferative index. CONCLUSION: Overexpression of IL-1beta and high microvessel
      density may have important roles in tumor cell proliferation and lymph node
      metastasis in IMPC.

PMID- 19094584
TI  - [Frequency of genetic aberrations in mucosa-associated lymphoid tissue lymphoma
      of different sites].
AB  - OBJECTIVE: To study the frequency of certain specific genetic aberrations,
      including t (11; 18)/API2-MALT1, t (1; 14)/IgH-bcl-10 and t (14; 18)/IgH-MALT1,
      in mucosa-associated lymphoid tissue (MALT) lymphoma of different sites. METHODS:
      One hundred and ninety-six cases of MALT lymphoma from Cancer Hospital of Fudan
      University were enrolled into the study. The samples consisted of MALT lymphomas
      from stomach (53 cases, including 44 cases of low-grade MALT lymphoma and 9 cases
      of MALT lymphoma with diffuse large B-cell lymphoma component), ocular adnexa (50
      cases), salivary gland (20 cases), lung (20 cases), intestine (17 cases), skin
      (17 cases), liver (8 cases), thyroid (5 cases) and other sites (2 cases from
      tongue, 1 case from pancreas, 1 case from larynx, 1 case from vocal cords and 1
      case from kidney). Fluorescence in-situ hybridization for API2-MALT1 fusion gene,
      bcl-10, MALT1 and IgH genes was performed on paraffin sections. RESULTS: Among
      the 196 cases of MALT lymphoma, 25 cases (12.8%) possessed API2-MALT1 fusion
      gene. The positive rates in various sites were significantly different (P =
      0.002), as follows: 45.0% (9/20) in lung, 22.7% (10/44) in stomach (without large
      cell component), 15.0% (3/20) in salivary gland, 2 of 17 cases in intestine and
      2.0% (1/50) in ocular adnexa. The fusion gene was not detected in the 9 cases of
      gastric MALT lymphoma with large cell transformation. It was also negative in the
      MALT lymphomas from skin, thyroid and other sites. One of the pulmonary MALT
      lymphoma cases showed simultaneous aberrations of IgH and MALT1 genes, such as t
      (14; 18)/IgH-MALT1. Two of the gastric MALT lymphoma cases without large cell
      transformation and one of the pulmonary MALT lymphoma cases showed aberrations in
      both IgH and bcl-10 genes, such as t (1; 14)/IgH-bcl-10. Six cases of MALT
      lymphoma, including 2 cases from salivary gland, 2 cases from liver, 1 case from
      thyroid and 1 case from stomach (large cell transformation), showed trisomy 18.
      On the other hand, 3 cases, including 2 cases from stomach and 1 case from
      intestine, showed MALT1 gene amplification. CONCLUSIONS: In general, specific
      genetic aberrations have a relatively low frequency of occurrence in MALT
      lymphomas. The positive rates however show a remarkable difference in tumors of
      different anatomic sites. This phenomenon may suggest that MALT lymphomas in
      different sites, though sharing similar morphologic features, may have a
      divergent tumorgenesis.

PMID- 19094585
TI  - [Clinicopathologic study of pilocytic astrocytoma].
AB  - OBJECTIVE: To study clinicopathologic features, treatment and prognosis of
      pilocytic astrocytoma (PA). METHODS: Histopathological, ultrastructural,
      immunohistochemical (EnVision method) and clinical features of 68 cases of PA
      were studied by microscopic investigation with correlation of clinical follow-up
      information when available. RESULTS: Thirty-five male patients and 33 female
      patients were studied. The patient's age ranged from 3 to 66 years (mean = 20.1
      years). The mean time from symptom onset to surgery was 371 days (range, 3 days
      to 14 years). Cystic degeneration was noted in 41 cases (60.3%), and enhancement
      of the tumor was noted in 43 cases (87.8%). On postcontrast imaging examination
      there were 33 cases involving the cerebellum (48.5%). Total tumor excision was
      performed in 35 patients, subtotal tumor excision was performed in 31 patients,
      and the procedures of other 2 patients were not clear. Among 51 patients with
      follow-up information, 44 were alive, 7 had recurrent tumor, and 7 died. The post
      operative survival ranged from 2 months to 124 months (mean survival = 48.1
      months). Five years and ten years survival rates were 89%, respectively. Tumors
      with classic histopathology demonstrated biphasic pattern of growth, consisting
      of compact elongated bipolar astrocytes associated with rosenthal fibers, and
      less cellular areas of multipolar cells with granular bodies and microcyst. Some
      cases showed atypia of nuclei, and occasional mitoses. Involvement of
      subarachnoid space was seen in 17 cases. One case had anaplastic features. All
      cases showed diffuse positive staining for GFAP and low expression for Ki-67,
      except 1 anaplastic tumor with 10% Ki-67 indices. Tumors with subarachnoid space
      involvement showed positive reticular fiber staining and negative EMA staining.
      CONCLUSIONS: PA is a benign, WHO grade I tumor with favorable prognosis, and does
      not require radiotherapy after total resection. The tumor can be mistaken as
      higher-grade astrocytoma when involving the subarachnoid space, and with
      cytological atypia, leading to unnecessary radiotherapy after surgery. Recurrence
      rate is increased when only partial resection is achieved. The outcome for
      patients with brainstem tumor or anaplastic PA is poor.

PMID- 19094586
TI  - [Relationship between expression of caveolin-1 and pERK1/2 and prognosis in non
      small cell lung cancer].
AB  - OBJECTIVE: To study the relationship between expression of caveolin-1 (Cav-1) and
      pERK1/2 and prognosis in non-small cell lung cancer (NSCLC). METHODS: Cav-1 and
      pERK1/2 protein expression was assessed by immunohistochemistry in samples
      obtained from 160 patients with NSCLC and 20 patients with normal lung tissue.
      RESULTS: Normal bronchial and alveolar epithelial cells were positive for Cav-1
      (membranous and cytoplasmic staining patterns). The expression rate of Cav-1 in
      NSCLC was 65.6% (105/160), which was significantly lower than that in normal lung
      tissue (P = 0.002). The Cav-1-positive rates in well to moderately differentiated
      tumors and poorly differentiated tumors were 56.8% (46/81) and 75.7% (53/70),
      respectively (P = 0.015). The expression of Cav-1 was much higher in patients
      with lymph node metastasis (77.8%, compared with 55.7% in lymph node-negative
      group, P = 0.003). The expression was also higher in stage III to IV than in
      stage I to II disease (75.4%, compared with 58.2%, P = 0.024). The overall
      survival of patients with Cav-1-positive tumors (71.4%, 37.1% and 17.1% 1-, 3-
      and 5-year survival, respectively) was lower than those with Cav-1-negative
      tumors (89.1%, 69.1% and 43.6% 1-, 3- and 5-year survival, respectively, P =
      0.000). On the other hand, normal bronchial and alveolar epithelial cells were
      negative for pERK1/2. The expression rate of pERK1/2 in NSCLC was 61.3%, which
      was significantly higher than that in normal lung tissues (P = 0.000). The
      pERK1/2-positive rates in well to moderately differentiated tumors and poorly
      differentiated tumors was 53.1% and 71.4%, respectively (P = 0.021). The
      expression of pERK1/2 was much higher in patients with lymph node metastasis
      (80.6%, compared with 45.5% in lymph node-negative group, P = 0.000). The
      expression of pERK1/2 was also higher in stage III to IV than in stage I to II
      disease (76.8%, compared with 49.5%, P = 0.426). The overall survival of patients
      with pERK1/2-positive tumors (74.5%, 42.9% and 19.4% 1-, 3- and 5-year survival,
      respectively) was lower than those with pERK1/2-negative tumors (82.3%, 56.5% and
      37.1% 1-, 3- and 5-year survival, respectively, P = 0.002). Cav-1 and pERK1/2
      expression showed negative correlation (P = 0.000). CONCLUSIONS: Cav-1 expression
      is lower in NSCLC than in normal lung tissue, whereas pERK1/2 expression is
      higher in NSCLC. Positive expression of Cav-1 and overexpression of pERK1/2
      correlates with tumorigenesis and tumor progression of NSCLC. Cav-1 and pERK1/2
      may serve as potential markers for predicting prognosis in NSCLC.

PMID- 19094587
TI  - [Influence of inhibited gene expression of alpha 3 nicotinic acetylcholine
      receptor by RNA interference on anti-oxidation in SH-SY5Y cells].
AB  - OBJECTIVES: To investigate the neuroprotective function of alpha 3 nicotinic
      acetylcholine receptor (nAChR) by inhibiting the gene expression in human
      neuroblastoma (SH-SY5Y) cells using small interference RNA (siRNA). METHODS: The
      siRNA coding oligonucleotide sequences targeting alpha 3 nAChR were designed and
      synthesized. The annealed product was cloned into pSilencer 3.1-H1 neo vector.
      The recombinant alpha 3 nAChR pSilencer 3.1-H1 neo vector was transfected into
      the SH-SY5Y cells. The stable clones were screened by G418 medium, and the levels
      of alpha 3 nAChR mRNA and protein were monitored by using real-time PCR and
      Western blotting, respectively. After the SH-SY5Y cells with siRNA treatment were
      exposed to 1 micromol/L Abeta(1-42), MTT [3-(4, 5-dimethylthiazol-2-yl)-2, 5
      diphenyltetrazolium bromide], SOD, GSH-px and the lipid peroxidation were
      measured by spectrophotometry. RESULTS: Compared with the controls, the
      expression levels of mRNA and protein in the stable SH-SY5Y clone cells
      transfected with the recombinant alpha 3 nAChR pSilencer 3.1-H1 neo vector were
      decreased with inhibitory efficiency of 98% and 66%, respectively, the MTT
      reduction decreased; the product of lipid peroxidation was increased and the
      activities of SOD and GSH-px were decreased. Biologically, the gene expression
      inhibition of alpha 3 nAChR enhanced the toxicity induced by Abeta in SH-SY5Y
      cells. CONCLUSIONS: The expression inhibition of alpha 3 nAChR as a result of
      recombinant alpha 3 nAChR siRNA can induce oxidative stress and improve the
      toxicity of Abeta on SH-SY5Y cells, indicating that alpha 3 nAChR may play a
      significant neuroprotective role in the pathogenesis of Alzheimer disease.

PMID- 19094588
TI  - [Study the role of PD98059 in ovarian carcinoma cell line HO-8910].

PMID- 19094589
TI  - [Updates on pathogenesis of ovarian tumors].

PMID- 19094590
TI  - [Advances in Sertoli-Leydig cell tumour of the ovary].

PMID- 19094591
TI  - [Inflammatory gynecologic conditions mimicking neoplastic growths].

PMID- 19094592
TI  - [Evaluation of different grading and staging systems of chronic hepatitis and
      problems in application].

PMID- 19094593
TI  - [Tumor mass of cranial frontal region].

PMID- 19094594
TI  - [Adenosarcoma arising in abdominal scar endometriosis: report of a case].

PMID- 19094596
TI  - [Clinical study of the method of hepatic vascular occlusion during resection of
      liver carcinoma].
AB  - OBJECTIVE: To evaluate the optimal method for hepatic vascular occlusion during
      resection of liver carcinoma. METHODS: One hundred and twenty-four patients with
      liver carcinoma were divided into four groups of hepatectomy with total hepatic
      inflow occlusion (group A, 51 cases), selective hepatic inflow occlusion (group
      B, 38 cases), selective exclusion of hepatic inflow and outflow (group C, 24
      cases) and total hemi-hepatic vascular exclusion (group D, 11 cases). The time of
      operation and hepatic vascular occlusion, intraoperative blood loss and
      transfusion, postoperative liver function, complications and mortality were
      compared among the four groups. RESULTS: There were no significant difference
      among the four groups statistically in preoperative basic states (P > 0.05). The
      duration of operation was prolonged significantly in group C and D than that of
      group A, but intra-operative blood loss and transfusion requirements were
      decreased significantly in group C and D versus group A and B (P < 0.05). There
      was no significant difference among the four groups regarding ischemia time,
      postoperative complications and mortality (P > 0.05). The level of postoperative
      alanine aminotransferase was higher in group A than other three groups (P <
      0.05). The postoperative total bilirubin increased significantly in group A
      contrast to group B (P < 0.05). CONCLUSIONS: Each hepatic vascular occlusion
      technique has its place in liver resection. The size and location of tumor,
      preoperative liver function, underlying liver disease, cardiovascular and
      cerebral vessels status, and most important the experience and capability to
      weigh the merits and demerits of the surgeon should be taken into account to
      select the most appropriate occlusion method.

PMID- 19094597
TI  - [Tumor proliferation and apoptosis after preoperative hepatic and regional
      arterial infusion chemotherapy in prevention of liver metastasis after colorectal
      cancer surgery].
AB  - OBJECTIVE: To investigate the tumor proliferation and apoptosis changes after
      preoperative hepatic and regional arterial infusion chemotherapy (PHRAIC) after
      radical colorectal cancer resection. METHODS: Five hundred and nine patients with
      stage II or stage III colorectal cancer from June 2001 to June 2007 were randomly
      assigned to PHRAIC group (n = 256) or control group (n = 253, surgery alone).
      Tumor proliferation and apoptosis index were evaluated in tumor tissues of the
      control and PHRAIC group (pre and after intervention). The survival rates were
      also recorded in the two groups. RESULTS: There was no significant differences in
      sex, age, tumor location, tumor size, tumor stage, tumor differentiation and
      follow-up time for the two groups (P > 0.05). There was no significant
      differences in all the evaluation factors between the control group and PHRAIC
      group before intervention (P > 0.05). Before and after intervention for PHRAIC
      group: stage 3 necrosis rate were 3.1% and 22.7%, stage 4 necrosis rate were 0
      and 13.5% (P < 0.05); label index of Ki67 were 48.6 +/- 17.1 and 38.4 +/- 13.3 (P
      < 0.05); expression rate of Bax, bcl-2 and survivin were 48.0% vs 77.0%, 75.0% vs
      43.0%, 52.0% vs 31.6%, respectively (P < 0.05); apoptosis rate were 4.3% +/- 2.2%
      and 16.7% +/- 6.4%(P < 0.05). In the PHRAIC group, 42.1% +/- 11.2% of the cells
      in the tumor tissue were in S phase before intervention and the rate fell to
      21.8% +/- 10.7% after intervention (P < 0.05); and G0-G1 phase rate of the group
      pre and post intervention were 35.1% +/- 12.1% and 57.1% +/- 18.1% (P < 0.05).
      All the patients were followed-up for a mean time of 42 +/- 14 months. For
      patients with stage III tumor in PHRAIC group and control group, the 5-year liver
      metastasis rate were 18.9% and 27.3% (P = 0.033), recurrence and metastasis rate
      were 26.3% and 38.0 (P = 0.024), overall survival rate were 81.0% and 60.4% (P =
      0.011), median survival time were 45 and 40 months (P = 0.02); no significant
      differences of aforementioned factors was found in patients with stage II tumors
      between the two groups. CONCLUSION: The schedule of preoperative hepatic and
      regional arterial infusion chemotherapy before surgery can restrain
      proliferation, promote apoptosis and reduce liver metastasis and improve survival
      rate in stage III colorectal cancer.

PMID- 19094598
TI  - [Use of local or epidural anesthesia in inguinal hernia repair: a randomized
      trial].
AB  - OBJECTIVE: To investigate the efficacy and safety of local anesthesia and
      epidural anesthesia in tension-free repair of inguinal hernia. METHODS: Between
      January 2004 and December 2006, 269 patients underwent inguinal hernia repair
      were randomly divided into two groups, receiving local anesthesia (143 cases) and
      epidural anesthesia (126 cases). The clinical data from the two groups were
      analyzed retrospectively. RESULTS: The operation time, ambulation time, length of
      hospital stay and cost of hospitalization in local anesthesia group were
      significantly less than those in epidural anesthesia group (P < 0.05). No
      significant differences were found in intra-operative use of ancillary sedation
      drugs, postoperative recovery situation, pain scores and operation-correlated
      complications between the two groups. The occurrence of postoperative anaesthetic
      complication rate was also significantly lower in local anesthesia group (P <
      0.05). One case of recurrence occurred in each group during postoperative follow
      up period. CONCLUSION: Tension-free inguinal hernia repair under local anesthesia
      is a simple, safe, economical, effective procedure and superior to epidural
      anesthesia.

PMID- 19094599
TI  - [The influence of thoracic kyphosis on sagittal balance of the lumbosacral spine
      in thoracic idiopathic scoliosis patients].
AB  - OBJECTIVES: To evaluate the influence of thoracic kyphosis to sagittal alignment
      and balance of the lumbosacral vertebrae in thoracic adolescent idiopathic
      scoliosis patients. METHODS: Standing posteroanterior and lateral x-rays of a
      cohort of 55 patients with thoracic adolescent idiopathic scoliosis were
      obtained. The patients were classified according to their thoracic kyphosis, the
      first group TK < 10 degrees and the second group 10 degrees < or = TK < or = 40
      degrees . The following parameters were measured: lumbar lordosis (LL), upper and
      lower arc of lumbar lordosis, sagittal vertical axis, sacral slope (SS), pelvic
      incidence (PI), pelvic tilt (PT). Sagittal plane parameters were analyzed using t
      test between two groups, with significance set at P < 0.05. Linear correlations
      between parameters were calculated using Pearson correlation coefficients, with
      significance set at P < 0.01. RESULTS: There were smaller LL and upper arc of
      lumbar lordosis in the first group. Significant linear correlations were found
      between each single adjacent shape parameter. Significant correlations were also
      found between TK, LL and upper arc of lumbar lordosis, as well as between PT, SS
      and PI. CONCLUSIONS: Sagittal alignment and balance of the lumbosacral vertebrae
      may influence the thoracic kyphosis in AIS patients. The mechanism of this
      influence may through the adaptation of upper arc of lumbar lordosis. This
      influence must be considered in thoracic adolescent idiopathic scoliosis patients
      who undergo selective posterior thoracic fusion.

PMID- 19094600
TI  - [Reliability of magnetic resonance imaging in diagnosing posterior ligament
      complex injury in thoracolumbar fractures].
AB  - OBJECTIVE: To analyze the reliability of magnetic resonance imaging (MRI) in
      detecting posterior ligament complex injury in thoracolumbar fractures. METHODS:
      Ninety-five patients with thoracolumbar fracture were evaluated by palpation of
      the inter-spinal gap, plain radiography, and MRI before operation. In addition to
      conventional MRI sequences, a fat-suppressed T2-weighted sagittal sequence was
      performed. Surgery was performed by a posterior approach. During the operation,
      posterior ligament complex was examined. RESULTS: A wide inter-spinal gap was
      palpated in 41 patients and was found in 55 patients on plain radiography.
      According to MRI, injury to the supraspinal ligament was suspected in 85
      patients, the inter-spinal ligament in 83 patients, and the ligamentum flavum in
      26 patients. There were 82 supraspinal ligament injuries, 80 inter-spinal
      ligament injuries, and 20 ligamentum flavum injuries in operative findings. The
      relations between plain radiography and operative findings, between MRI
      interpretation and operative findings were statistically significant. CONCLUSION:
      A fat-suppressed T2-weighted sagittal sequence of MRI is a highly sensitive,
      specific, and accurate method to detect posterior ligament complex injury and
      which is recommended for the accurate evaluation of posterior ligament complex
      injury in thoracolumbar fractures.

PMID- 19094601
TI  - [Safety analysis of laparoscopic adrenalectomy for adrenal pheochromocytoma of 5
      to 10 cm].
AB  - OBJECTIVE: To investigate the safety of laparoscopic adrenalectomy for adrenal
      pheochromocytoma with maximum diameter of 5 - 10 cm. METHODS: Retrospective
      analysis was performed for 79 consecutive patients who underwent adrenalectomy
      for adrenal pheochromocytoma between January 2001 and June 2007. Forty-one
      patients among these cases had tumors of maximum diameter of 5 - 10 cm. Nine
      patients who underwent laparoscopic procedures (the additional 2 cases were
      converted to open surgery and were excluded) were compared with 30 patients who
      underwent open procedures using two-tailed unpaired t tests or Mann-Whitney U
      tests. RESULTS: There was no significant difference in age, maximum diameter of
      tumor, the highest preoperative systolic/diastolic pressure, the preoperative
      heart rate and the plasma catecholamines between the two groups (P > 0.05). All
      laparoscopic procedures were performed by retroperitoneal approach. For open
      surgeries, 11 were performed by transperitoneal approach and 19 by
      retroperitoneal approach. We found significant differences between laparoscopic
      and open groups in the operative time, the blood loss, and postoperative hospital
      stay. Blood-transfusion was not required in the laparoscopic group and the median
      volume of blood-transfusion in the open group was 225 ml (0 - 3800 ml). No
      significant differences were found in intraoperative maximum and minimum blood
      pressures, maximum and minimum heart rates, systolic blood pressure increased by
      30% from the preoperative baseline, systolic blood pressure > or = 200 mm Hg (1
      mm Hg = 0.133 kPa), systolic blood pressure < or = 90 mm Hg, incidence of
      tachycardia (> or = 110 bpm) and bradycardia (< or = 50 bpm) (P > 0.05). And the
      drainage volume, drainage time, duration in ICU, time to first oral intake and
      cost of hospitalization were not significantly different between the two groups
      (P > 0.05). CONCLUSIONS: For adrenal pheochromocytoma with maximum diameter of 5 
      10 cm, the laparoscopic procedure decreased operative time, blood loss, blood
      transfusion and postoperative hospital stay compared to traditional open surgery.
      Intraoperative hemodynamic values during laparoscopic adrenalectomy are
      comparable to those of traditional open surgery. Adrenal pheochromocytoma of 5 -
      10 cm is not a contraindication of laparoscopic surgery and experienced
      urologists can perform it safely for large adrenal pheochromocytoma.

PMID- 19094602
TI  - [A study of the different effect on the expression of calcitonin gene related
      peptide and neuropeptide Y in tissue engineered bone with vascular bundle graft
      in vivo and that with sensory nerve tract graft in vivo].
AB  - OBJECTIVE: To evaluate the different effect on the expression of Calcitonin gene
      related peptide (CGRP)and neuropeptide Y (NPY) between tissue engineered bone
      with vascular bundle graft in vivo and that with sensory nerve tract graft in
      vivo. METHOD: Thirty-six healthy New Zealand rabbits were divided into 3 groups
      randomly and equally: vascular bundle group (A), sensory nerve tract group (B),
      tissue-engineering group (C). Group A segmental bone defect of 1.5 cm long was
      made at the right femur in each animal. After plate fixation, the defects were
      implanted respectively with the engineered bone prepared in the above-mentioned 3
      methods. At 3, 6 and 12 months post-operatively, the distribution of CGRP and NPY
      in the new bone were detected by immunohistochemistry and analyzed semi
      quantitatively by image analysis software. RESULTS: CGRP and NPY immuno
      histochemical results indicated their contents increased significantly in all 3
      groups as time passed (P = 0.000). Compared with group B, the contents of CGRP
      and NPY in group A significantly increased at 3 months (P = 0.000), but there was
      no statistic difference between them at 6 or 12 months (P > 0.05). The expression
      of CGRP and NPY in both group A and B were significantly more than that in group
      C at 3, 6 or 12 months (P = 0.000). CONCLUSION: Implantation of vascular bundle
      into tissue-engineered bone can significantly improve the CGRP and NPY contents
      at early 3 months comparing with Implantation of sensory tract into tissue
      engineered bone, but the changes are not significant at 6 or 12 months post
      operatively.

PMID- 19094603
TI  - [Intervention of Poloxamer 188 to chondrocyte damaged by blunt mechanical trauma
      in vitro].
AB  - OBJECTIVE: To explore Poloxamer 188, a non-ionic surfactant as a potential tool
      for early intervention into the chondrocyte damaged by blunt mechanical trauma in
      vitro. METHODS: Three groups were control group (n = 6), no treatment group (n =
      12) and Poloxamer 188 treatment group (n = 12). Two groups are then loaded to 20
      MPa in unconfined compression. At 1 and 24 h the percentages of live and dead
      cells of superficial zone in compressed and control groups were determined with a
      cell viability stain. RESULTS: At 1 h post-trauma, specimens of Poloxamer 188
      treatment group (76%) had a significantly increased percentage of live cells in
      the superficial zone versus the no treatment group (55%). In 24 h the percentages
      of live cells in the superficial zone of the Poloxamer 188 treatment group (57%)
      were significantly greater than in the no treatment group (38%). CONCLUSIONS:
      Poloxamer 188 surfactant could help restore the integrity of cell membranes in
      cartilage damaged by blunt mechanical trauma. Models of mechanical cartilage
      injury in vitro may explain aspect of the interactions between mechanical forces
      and degradative pathways which lead to osteoarthritis progression.

PMID- 19094618
TI  - [Liver resection in hepatolithiasis: 20-year's evolution].
AB  - OBJECTIVE: To analyze operative and perioperative factors associated with
      hepatectomy in hepatolithiasis. METHODS: 245 consecutive hepatolithiasis patients
      undergoing hepatectomy from January 1986 to December 2005 at Chinese People's
      Liberation Army General Hospital were investigated retrospectively according to
      medical documentation. RESULTS: Hepatolithiasis accounted for 29.6% (245/827) in
      all benign liver diseases treated with hepatectomy during this time period. There
      were 88 cases in male and 157 cases in female, the average age was (46.9 +/-
      11.3) years. Cases of right liver resection and hepatic segments resection were
      much more than that in 1963 - 1985. Blood transfusion during operation was given
      in 45.3% of cases. Complication incidence was 16.3%, with infection 3.3% and bile
      leakage 2.4%. Length of stay after operation was (15.7 +/- 9.2) days.
      Perioperative mortality rate was 0.4% (1/245). CONCLUSIONS: Individualized
      hepatectomy is the important surgical treatment of hepatolithiasis. Hepatectomy
      can be performed safely with low mortality and low complication incidence,
      provided that it is carried out with optimized perioperative management and
      innovative surgical technique.

PMID- 19094619
TI  - [Emergency right lobe adult-to-adult live-donor liver transplantation for the
      treatment of acute liver failure following severe hepatitis].
AB  - OBJECTIVE: To research the clinical feasibility of emergency right lobe adult-to
      adult live-donor liver transplantation in treating acute liver failure following
      severe hepatitis. METHODS: Consecutive ten severe hepatitis patients (4 acute-on
      chronic severe hepatitis and 6 acute severe hepatitis; 9 caused by HBV and 1 with
      drug-induced acute liver failure) underwent emergency right lobe adult-to-adult
      live-donor liver transplantation in our hospital from April 2007 to December
      2007. The +/- s of model for end-stage liver disease score was 33.22 +/- 6.55.
      The outcomes of these recipients were prospectively analyzed. RESULTS: Among
      them, 8 ABO blood group were identical and 2 compatible. One was Rh sub-group
      negative. Except 2 recipients died (1 acute renal failure caused by veno cava
      thrombosis, 1 liver graft lose caused by hepatic artery thrombosis), the rest of
      recipients (80%) and all donors were safe. The mean graft-to-recipient weight
      ratio was (1.19 +/- 0.14)%, and graft volume to recipient estimated standard
      liver volume ratio was (65.13 +/- 8.75)%. Right lobe grafts with middle hepatic
      vein (MHV) 3 cases, without MHV 4 cases, without MHV but followed by V and VIII
      hepatic vein outflow reconstruction 3 cases. Encouraging outcome was achieved in
      this group of recipient: elevated serum creatinine, serum endotoxin, decreased
      serum prothrombin activity (PTA) and total bilirubin returned to normal about on
      postoperative day (POD) 3, POD 7, POD 14 and POD 28, respectively. CONCLUSIONS:
      Outcomes of emergency right lobe adult-to-adult live-donor liver transplantation
      for acute hepatic failure following severe hepatitis are fairly encouraging and
      acceptable. emergency right lobe adult-to-adult live-donor liver transplantation
      is an effective and life-saving modality for acute liver failure following severe
      hepatitis.

PMID- 19094620
TI  - [The value of spleen sub-pedicle two steps severance with LigaSure in
      laparoscopic splenectomy].
AB  - OBJECTIVE: To evaluate the safety and utility of the methods of spleen sub
      pedicle two steps severance with LigaSure Vessel Sealing System combined with
      ultrasound scalpel to resect peri-splenic ligaments during laparoscopic
      splenectomy. METHODS: The methods and the curative effect of 32 patients with
      laparoscopic splenectomy performed by the way as mentioned above were summarized
      and analyzed. 4 males, 28 females, median 36 years (range 16 - 64 years). Mean
      dimensions of spleens were 17 cm (range 11 - 23 cm). Nineteen patients had
      idiopathic thrombocytopenia purpura (ITP), 6 hereditary spherocytosis (HS) (5 of
      them were the same family constellation), 3 hemolytic anemia (HA), 2 spleen
      injury with haematoma infection, 1 Evan syndrome, 1 leukemia. Peri-splenic
      ligaments were resected by LigaSure combined with ultrasound scalpel, splenic
      pedicle was resected by spleen sub-pedicle two steps severance with LigaSure when
      splenic pedicle were sufficiently free. Splenic pedicle was non-excisional
      occluded by LigaSure at pancreatic cauda, in the first step and was occluded and
      resected alongside of the spleen in the second step. RESULTS: All of the 32 cases
      were completely succeed, the average operating time was 70 min (55 - 130 min),
      the estimated intraoperative blood loss was 200 ml (50 - 600 ml), no
      complications such as abdominal haemorrhage, visceral injury, pancreatic leakage
      and infection were observed. All the patients were healed well, the average
      hospital stay after an operation was 6 days. The average expense of each patients
      could save 8050 yuan because Endo-GIA was not used. CONCLUSIONS: Spleen sub
      pedicle two steps severance with LigaSure Vessel Sealing System combined with
      ultrasound scalpel to resect peri-splenic ligaments during laparoscopic
      splenectomy, which shorten the operating persistence time with less hemorrhage is
      a safe, effective and low-cost minimally invasive surgery in selective cases.

PMID- 19094621
TI  - [The efficacy of preoperative portal vein embolization for extended hepatectomy:
      a meta-analysis].
AB  - OBJECTIVE: To investigate the clinical value of preoperative portal vein
      embolization (PVE) for extended hepatectomy. METHODS: A comprehensive Pubmed,
      Medline and Ovid database search to identify all registered literature on portal
      vein embolization. Meta-analysis was performed to assess the result of PVE.
      RESULTS: A total of 9 literatures provided data sufficiently enough for analysis
      involving in 494 patients. The results showed that postoperative liver failure
      was higher in the non-PVE group than the PVE group, but there was no difference
      in postoperative mortality between the PVE and non-PVE group; in sub-category
      analysis of hepatocellular carcinoma and liver metastasis of colorectal cancer,
      there was no difference in postoperative 1, 3 and 5-year survival rate between
      the PVE group and non-PVE group; 1 literature about liver metastasis of
      colorectal cancer show there was significant difference in postoperative
      metastasis between the PVE and non-PVE group; several patients after PVE didn't
      performed hepatectomy due to disease progress. CONCLUSIONS: PVE is a safe and
      effective procedure to prevent postresection liver failure due to insufficient
      liver remnant, but surgeon should be cautious to choose the patient for PVE.

PMID- 19094622
TI  - [Comparative study of ultrasonography, magnetic resonance
      cholangiopancreatography and endoscopic retrograde cholangiopancreatography in
      common duct stones].
AB  - OBJECTIVE: To compare the diagnostic value study the technique of
      ultrasonography, magnetic resonance cholangiopancreatography (MRCP) and
      endoscopic retrograde cholangiopancreatography (ERCP) in common duct stones.
      METHODS: Three hundreds and eighty-four patients suspected common duct stones
      from August 2005 to October 2007 were undergone abdominal ultrasonography, MRCP
      and ERCP. RESULTS: There was stone in common duct in 370 and no stones in 14 of
      384 patients. Ultrasonography indicated stones 268 cases, 8 false positive result
      was among them. MRCP diagnosed stones in 362 cases and false positive result in 6
      cases, ERCP diagnosed stones 370 cases. The diagnostic accuracy of
      ultrasonography, MRCP and ERCP was 70.3% (260/370), 96.2% (356/370) and 100%
      respectively. CONCLUSIONS: The diagnostic accuracy of ultrasonography for common
      duct stone was little higher, US should be used as a primary checking method.
      There was higher concordance between MRCP and ERCP for common duct stone.
      Combination of MRCP and ERCP can improve diagnostic accuracy of common duct
      stone.

PMID- 19094623
TI  - [Clinicopathologic features and prognosis of gastric cancer in young adults].
AB  - OBJECTIVE: To analyze the clinicopathologic features and prognosis of young
      patients with gastric cancer by comparing with older patients. METHOD: The
      clinicopathologic data of 157 younger adults (age, </= 40 years) with gastric
      cancer and 1761 cases of elder gastric cancer patients (age, > 40 years) was
      analyzed and compared retrospectively. All of the 1918 patients were surgically
      treated between January 1980 and December 2000. RESULTS: The rates of poorly
      differentiation, diffusive growth, Borrmann 4 type, whole-stomach invasion were
      significantly higher in younger cases than those in the elder counterparts (P <
      0.05), especially in young female patients. The rate of early gastric cancer was
      significantly higher in young patients than that in older patients (P < 0.05),
      especially in young male patients. There was significant difference between the
      survival rate of younger male cases (median survival, 35 months) and younger
      female cases (median survival, 19 months) (P = 0.0219), but no significant
      difference was found between elder male and elder female (median survival, 26 vs.
      30 months). TNM stage, operative curability, gross type were independent
      predictive factors of survival for younger patients. CONCLUSIONS: Younger female
      gastric cancer patients tends to have worse prognosis than older patients, while
      younger male patients have better prognosis due to higher percentage of early
      gastric cancer when diagnosed. Pathologic staging and operative curability are
      the independent predictive factors of survival for younger patients.

PMID- 19094624
TI  - [Sonographically guided intralesional sclerotherapy for venous malformation].
AB  - OBJECTIVE: To investigate the safety and efficacy of sonographically guided
      percutaneous intralesional sclerotherapy for peripheral venous malformations.
      METHODS: From March 2004 to October 2007, 32 patients with venous malformations
      of soft tissues were treated with sonographically guided intralesional
      sclerotherapy. The malformed venous space was identified intraoperatively by
      duplex scanning, the gauge 7 needle was inserted into this venous space under
      real-time ultrasound visualization, and sclerosants were infused in the space
      gently. Absolute alcohol and bleomycin acted as sclerosants here, combined the
      two (for type I malformation) or bleomycin only (for type II malformation). The
      treatment could be repeated if the lesion was not cured in 3 weeks. All patients
      were followed up for 6 months to 2 years. RESULTS: Of the group, each patient
      received 1 - 6 times of the therapy (mean, 3 times). Twenty-seven patients
      achieved a complete response, and 5 achieved partial response. No major
      complications occurred. CONCLUSIONS: Sonographically guided percutaneous
      intralesional sclerotherapy for peripheral venous malformation is a simple,
      effective, safe therapy with minimal invasion, lower morbidity rate, and can be
      repeated.

PMID- 19094625
TI  - [Micro-endoscopic strategies and options for recurrent lumbar disc herniation].
AB  - OBJECTIVE: To evaluate the results of micro-endoscopic revision surgery for
      recurrent disc herniation, and compare the results of disc excision with and
      without interbody fusion. METHODS: A total of 32 patients included who had
      undergone micro-endoscopic revision discectomy for recurrent disc herniation with
      or without interbody fusion has been surveyed to assess their clinical outcome.
      The 27 patients who had been followed were divided into two groups; the micro
      endoscopic discectomy alone 14 cases, the micro-endoscopic discectomy with
      interbody fusion 13 cases. With an average follow-up of 25.5 months. Clinical
      symptoms were assessed based on the VAS scores and Nakai criteria. All medical
      and surgical records were examined and analyzed, including intraoperative blood
      loss, length of surgery, and postsurgery hospital stay et al. RESULTS: The
      statistical difference in the postoperative back pain and leg pain score compared
      with preoperative score were significant (P < 0.05) or very significant (P <
      0.01). Clinical outcomes were excellent or good in 92.8% of patients undergoing a
      micro-endoscopic discectomy alone, and in 85.5% of patients with interbody
      fusion. The statistical difference between the fusion and non-fusion groups was
      insignificant (P = 0.793). But the two groups intraoperative blood loss, length
      of surgery, length of hospitalization and expenses were significantly less in
      patients undergoing discectomy alone than in patients with interbody fusion.
      CONCLUSIONS: Micro-endoscopic revision surgery for recurrent disc herniation is
      very effective and safety. Micro-endoscopic discectomy alone is first choice for
      managing recurrent disc herniation.

PMID- 19094626
TI  - [Endoscopic thyroidectomy through anterior chest and breast approach for
      papillary thyroid microcarcinoma].
AB  - OBJECTIVE: To evaluate the operative feasibility and safety of endoscopic
      thyroidectomy through anterior chest and breast approach for the treatment of the
      patients with papillary thyroid microcarcinoma (PTMC). METHODS: Endoscopic
      thyroidectomy was attempted in 164 patients with thyroid diseases. For 28 cases,
      which were diagnosed as PTMC by frozen section intraoperatively, lobotomy plus
      central compartment dissection and contralateral subtotal lobotomy was achieved
      completely by endoscopic thyroidectomy. There were 27 females and 1 male, and
      their average age was 35.2 years old. Twelve and sixteen cases were diagnosed
      preoperatively as thyroid microcarcinomas and benign tumors, respectively.
      RESULTS: The operation time of the 28 cases was (115 +/- 43) min. The maximum
      diameter of PTMC was 0.2 to 1.0 cm with a mean of 0.56 cm. 17.9% (5/28) of the
      PTMC patients had transient vocal cord palsy and restored after 1 to 2 months
      postoperatively. There were no complications such as subcutaneous emphysema and
      postoperative bleeding and postoperative hypocalcaemia. 46.4% (13/28) had node
      involvement of the central compartment. Postoperative ultrasonography and
      scintigraphy showed no evidence of recurrence or residual thyroid tissue in the
      thyroid bed where lobotomy was performed. CONCLUSIONS: The endoscopic
      thyroidectomy through anterior chest and breast approach is a choice of the
      surgical treatment for selected cases of PTMC.

PMID- 19094627
TI  - [Surgical treatment of asymptomatic primary hyperparathyroidism].
AB  - OBJECTIVE: To discuss the diagnosis and management of asymptomatic primary
      hyperparathyroidism (PHPT). METHODS: Clinical data of 46 cases of primary
      hyperparathyroidism from January 1990 to December 2006 were retrospectively
      analyzed. There were 5 cases of asymptomatic PHPT. Three out of the 5 cases
      obtained the diagnosis by routine health examination and 1 case was misdiagnosed
      as thyroid tumor before surgery, but was conformed as parathyroid adenoma by
      intraoperative biopsy. Remaining 1 case was diagnosed because of weakness. The
      serum calcium and the parathyroid hormone (PTH) levels were elevated in 4 cases,
      while only 1 being normal range. Unilateral neck exploration was performed in all
      5 cases. RESULTS: There were no operational death, recurrent nerve injury or
      other complications. All patients had the same pathological diagnosis as
      parathyroid adenomas. Three cases showed gentle circumoral paresthesia after
      surgery with normal serum level of calcium, but the symptoms were relieved with
      oral use of calcium gluconate. Only 1 patient had tetany with the lowest level of
      serum calcemia at 1.96 mmol/L in 24 h postoperatively. The signs and symptoms
      were all relieved by intravenous use of calcium gluconate for 3 d after surgery.
      Remaining 1 case has normal level of serum calcemia after surgery. Time range of
      following-up for 4 cases was from 2 months to 2 years. The level of serum
      calcemia was normal for them. One lost following-up. CONCLUSIONS: Asymptomatic
      primary hyperparathyroidism could be diagnosed according to co-elevated serum
      calcemia and PTH without typical symptoms. Unilateral neck exploration was the
      best choice for the patients with accurate imaging localization. Conservative
      management including adequate hydration, dietary calcium intake and
      pharmacological approaches could be used for the patients who were unfit for
      surgery.

PMID- 19094628
TI  - [Resection and reconstruction of upper thoracic tumor by high transthoracic
      approach].
AB  - OBJECTIVES: To define the role of high transthoracic approach in the treatment of
      cervicothoracic and high thoracic tumor, and analyze the problem encountered
      during tumor resection and reconstruction of this technique and oncological
      results of patients who received this type of surgery. METHODS: Twenty-one
      patients with cervicothoracic and high thoracic tumor (T(1 - 4)) were treated
      with high transthoracic approach. This series included metastatic tumor 11
      patients, eosinophilic granuloma of bone 2 patients, osteosarcoma 1 patient,
      Ewing's sarcoma 2 patients, chondrosarcoma 2 patients, giant cell tumor 2
      patients, lymphoma 1 patient. High transthoracic approach was applied to these
      patients for tumor resection and spinal cord decompression. Reconstruction method
      included artificial vertebrae implantation or bone graft implantation combined
      with anterior internal fixation. RESULTS: Chest-back pain of all patients
      relieved significantly after operation. Paraplegia of 3 patients was improved
      from grade A to grade D according to Frankel grading system, the other 2 patients
      recovered completely. Pulmonary infection and pulmonary atelectasis occurred in 2
      patients; cerebrospinal fluid leakage happened in 1 patient; thoracic aorta
      rupture happened in 1 patient. The follow-up period was 11 - 58 months, 9
      patients died, including 7 patients with metastatic cancer, 1 patient with
      Ewing's sarcoma, 1 patient with osteosarcoma. CONCLUSIONS: High transthoracic
      approach is a satisfactory method in dealing with the lesion of cervicothoracic
      and high thoracic vertebrae, especially with the lesion involving the vertebrae
      and single vertebral arch. The thoracic canal can be decompressed effectively by
      this approach.

PMID- 19094629
TI  - [Reconstruction and balance of soft tissue in hemi-shoulder replacement for
      patients with four-part fracture of the proximal humerus].
AB  - OBJECTIVE: To explore the effective skills of reconstruction and balance of soft
      tissue in hemi-shoulder replacement for patients with four-part fracture of the
      proximal humerus in order to avoid postoperative complications of joint
      instability and great tubercle displacement. METHODS: From June 2002 to June
      2006, 25 patients with Neer four-part fracture of the proximal humerus were
      adopted in the study which included 15 females and 10 males, with the mean age of
      66 years (ranged from 56 years to 80 years). They were treated with humeral head
      replacement and should joint reparation simultaneously by modified operation
      approach and reconstruction and balance skills of soft tissue. RESULTS: The mean
      duration of follow-up was 2.3 years (ranged from 1 to 4.5 years). No infection,
      nerve damage and prosthesis loosing were found in all cases. Two cases of infra
      forward dislocation or subluxation occurred due to affected limb placed on
      abduction splint postoperatively. One case occurred prosthesis upward
      displacement due to early active abduction exercise but no complains. Neither
      joint instability nor displacement and malunion of great tubercle were found in
      other patients. According to Neer scoring system, 6 cases were rated as
      excellent, 15 as good and 5 as fair. The good and excellent rate was 84%.
      CONCLUSION: In hemi-shoulder replacement for patients with Neer four-part
      fracture the modified operation approach and reconstruction and balance of soft
      tissue skills combined with rational rehabilitation exercise can prevent
      postoperative shoulder joint instability and displacement and malunion of great
      tubercle.

PMID- 19094630
TI  - [Urodynamic analysis of the chronic impairment of cauda equina caused by lumbar
      disk herniation].
AB  - OBJECTIVE: To evaluate the urodynamic characteristics of the chronic impairment
      of cauda equina caused by lumbar disk herniation. METHODS: Clinical data and
      urodynamic parameters of 67 male patients with lumbar disk herniation were
      retrospectively analyzed. Lower urinary obstruction was excluded from the cohort
      using the Lin-PURR analysis. Patients were divided into group A (normal detrusor
      function), group B (detrusor underactivity) and group C (detrusor areflexia)
      according to the detrusor contraction function analyzed in Lin-PURR. Clinical
      data and urodynamic parameters were analyzed statistically between these groups.
      RESULTS: The category of the detrusor contraction function had a significant
      effect on the urodynamic parameters. There were significant differences in the
      maximum flow rate (Q(max)), maximum pressure (P(max)), pressure at the maximum
      flow (P(det Qmax)) and post-voiding residual urine (PVR) among group A, B and C.
      There were significant differences in the first sensation volume of the bladder
      and the maximum cystometric capacity between group A and C, B and C, but no
      significance was found between group A and B. There was no significant difference
      in age, disease duration, and compliance of the bladder among 3 groups.
      CONCLUSIONS: Urodynamic study is important in exploring the severity of the
      chronic impairment of cauda equina caused by lumbar disk herniation. Detrusor
      areflexia and loss of bladder sensory indicate more severe degree of impairment
      of the cauda equine. Q(max) and PVR are helpful in early diagnosis of the chronic
      impairment of cauda equina.

PMID- 19094631
TI  - [The use of recombinant activated factor VII for blood loss after cardiovascular
      surgery].
AB  - OBJECTIVE: To describe the early experiences with rFVIIa in the management of
      bleeding after cardiovascular surgery. METHODS: From May 2006 through December
      2007, 16 patients received rFVIIa during or after surgery despite conventional
      medical therapy and transfusion of blood products. There were 15 male patients
      and 1 female patients, aged from 36 to 77 years old with a mean of 52 years old.
      The surgical procedures include aortic procedures for 8 cases, valve replacement
      for 6 cases, pulmonary thromboendarterectomy for 1 case and atrial septal defect
      repair for 1 case. The data of these patients were reviewed and the safety and
      efficacy of rFVIIa after cardiovascular surgery were evaluated. RESULTS: rFVIIa
      was administered as a first dose of 27.6 to 54.5 microg/kg with a mean of 40.2
      microg/kg. Six patients achieved hemostasis after the first dose. Nine patients
      received a second administration within 30 min, with a cumulative dose of 59.3 to
      90.9 microg/kg, a mean of 80.3 microg/kg. Eight patients achieved hemostasis and
      1 patient went to exploration. One patient received four doses of rFVIIa with a
      cumulative dose of 203.4 microg/kg and the bleeding stopped. Mean amount of chest
      drain loss and the amount of red blood cell, fresh frozen plasma,
      cryoprecipitate, and platelet transfusions decreased significantly after rFVIIa
      administration. The total amount of chest drain losses, transfusions of red blood
      cell and cryoprecipitate within 12 h postoperatively was positively correlated
      with the time from the end of bypass to administration of rFVIIa. No
      thromboembolic complications and other adverse reactions were noted. CONCLUSIONS:
      The use of rFVIIa is associated with reduced blood loss, rapid improvement of
      coagulation variables, and decreased need for blood products. rFVIIa is safe and
      efficacious in the management of refractory postcardiotomy bleeding.

PMID- 19094632
TI  - [The clinical significance of heparanase expression in human pancreatic carcinoma
      tissue].
AB  - OBJECTIVE: To investigate the relationship between heparanase 1 (Hpa1) expression
      and the development of human pancreatic cancer. METHODS: Real-time PCR and
      Western blot methods were used the expression of Hpa1 in 37 cases of pancreatic
      cancer were analyzed quantitatively. The relationship between the expression of
      Hpa1 and the clinicopathological features of pancreatic cancer was analyzed.
      RESULTS: The expression of Hpa1 mRNA in pancreatic cancer was 23.53 +/- 4.13, in
      pancreatic tissues was 4.08 +/- 2.14 and in pancreatic cancer adjacent tissue was
      16.93 +/- 3.06 by real-time PCR detected (P < 0.01). The expression of Hpa1
      protein in normal tissue was 0.36 +/- 0.14, in pancreatic cancer adjacent tissue
      was 1.21 +/- 0.37 and in pancreatic cancer tissue was 1.76 +/- 0.28 by Western
      blot detected (P < 0.05). The expression of Hpa1 mRNA and Hpa1 protein in
      pancreatic cancer tissue were both higher than pancreatic cancer adjacent tissue
      and normal tissue. The expression of Hpa1 was significant associated with TNM
      grade and Invasion to nerves or vascellum lymph node metastasis separately (P <
      0.05). But no relationship between histological differentiation and the tumor
      size (P > 0.05). CONCLUSIONS: The Hpa1 overexpressed in pancreatic cancer tissues
      and its abnormal expression may be involved in the oncogenesis and development of
      pancreatic cancer.

PMID- 19094643
TI  - [Video-urodynamic studies on 1800 patients with neurogenic bladder].
AB  - OBJECTIVE: To explore the Video-urodynamic characteristics of various neurogenic
      bladder. METHODS: A total of 1800 patients with neurogenic bladder were included
      in our study from December 2002 to June 2008. All patients underwent Video
      urodynamic studies. Urodynamic data was collected and analyzed. RESULTS:
      Urodynamic study showed detrusor overactivity in 71%, of which 60% with
      uninhibited sphincter relaxation, and acontractile detrusor in 29% stroke
      patients. No upper urinary tract deterioration was found in all 42 stroke
      patients. Detrusor overactivity without sphincter dyssynergia was found in 70%
      patients with head trauma. Seven patients with Parkinson disease showed detrusor
      overactivity, of which 3 with delayed sphincter relaxation. Detrusor overactivity
      was found in 91% and detrusor sphincter dyssynergia in 83% supra-sacral spinal
      cord injured patients. Acontractile detrusor was found in 73% patients with conus
      medullaris and cauda equina injury. Overall, upper urinary tract changes were
      found in 12% and vesicoureteral reflux in 4% spinal cord injured patients.
      Urodynamic study showed acontractile detrusor in 81%, reduced compliance in 86%,
      upper urinary tract changes in 55% and vesicoureteral reflux in 33% patients with
      myelodysplasia. Most patients (92%) with protruded lumbar disc showed detrusor
      areflexia. Normal bladder compliance was found in 88% patients with protruded
      lumbar disc. Urodynamic study showed reduced bladder sensation in 81% and
      detrusor under-activity in 76% patients with diabetic urinary bladder disease.
      CONCLUSIONS: Video-urodynamic study can provide the most detailed information
      about the bladder dysfunction. It is the most valuable examination before
      treatment of patients with neurogenic bladder.

PMID- 19094644
TI  - [A multicenter study of mid urethral sling procedures in treatment of female
      stress urinary incontinence].
AB  - OBJECTIVE: To investigate the clinical efficacy, surgical indications and
      postoperative complications of mid urethral sling procedures in treatment of
      female stress urinary incontinence. METHODS: A multicenter clinical trial was
      conducted from April 2002 to April 2008 in five hospitals, 304 cases of genuine
      stress urinary incontinence and 8 cases of mixed incontinence were included. TVT
      procedures were carried out in 134 patients, TVTO procedures in 167 patients,
      Monarc procedures in 11 patients. Perioperative evaluations included: operating
      time, bleeding volume, and perioperative complications. Operative efficacy was
      classified into three categories: cure, improved and failure and evaluated before
      discharge, 3 months after surgery and then every year. RESULTS: TVT group had
      longer operating time [(18.5 + or - 9.6) min] and more bleeding volume [(32.2 +
      or - 12.6) ml] than those in TVTO group [(11.5 + or - 3.1) min, (12.8 + or - 8.5)
      ml] and in Monarc group [(11.1 + or - 2.6) min, (12.3 + or - 3.5) ml] with P <
      0.05. Monarc and TVTO procedures had higher cure rates and improve rates
      comparing with TVT, but the differences were of no significance. The cure rate
      (95.7%) in patients with genuine stress incontinence were significantly higher
      than that in patients with mixed incontinence (37.5%). No significant differences
      of total intra- and postoperative complications were noted for all of the three
      procedures. However, bladder injury tended to occur in TVT group and obturator
      nerve injury and vaginal injury tended to occur in TVTO group. Transient voiding
      dysfunction and urinary retention were the most common complications.
      CONCLUSIONS: Mid urethral sling procedures have excellent clinical outcomes in
      the treatment of female stress urinary incontinence.

PMID- 19094645
TI  - [Clinical study on concomitant surgery for stress urinary incontinence and pelvic
      organ prolapse].
AB  - OBJECTIVE: To discuss indications and therapeutic effects of concomitant surgery
      for stress urinary incontinence (SUI) and pelvic organ prolapse (POP) through a
      retrospective clinical review. METHOD: A retrospective review of the data of 16
      women undergoing concomitant surgery for SUI and POP was available for analysis.
      In these cases, 12 patients presented with SUI symptoms associated with moderate
      or severe anterior vaginal wall prolapse; 4 patients had moderate or severe
      uterine prolapse associated with dysuria. All cases were confirmed to have type
      II stress urinary incontinence by preoperative physical examination, urodynamic
      study and cystography. The surgical procedures for pelvic floor repair included
      the placement of Gynemesh mesh implant, anterior or total Prolift mesh implant.
      The tension-free vaginal tape (TVT) or transvaginal tension free vaginal tape
      obturator (TVT-O) was used for the anti-incontinence procedure. During the
      concurrent surgical procedures, pelvic floor repair was performed first. RESULTS:
      Followed up from 6 to 30 months, all cases got satisfactory results. After the
      procedure, the patients achieved complete continence without occurrence of
      dysuria or recurrence of POP. CONCLUSIONS: Stress incontinence and pelvic organ
      prolapse share common pathophysiologic etiologies and often coexist with one
      another. In SUI patients with symptomatic or moderate to severe POP, concurrent
      POP surgery should be performed actively at the time of incontinence surgery to
      prevent POP exacerbation and the occurrence of dysuria; while in patients with
      sole POP, occult SUI should be considered, and concomitant prophylactic
      incontinence measures should be taken at the time of POP repair to prevent the
      postoperative unmasking of SUI.

PMID- 19094646
TI  - [The long-term outcome of Studer neobladder and associated complications].
AB  - OBJECTIVE: To investigate the long-term outcome and related complications in a
      group of patients underwent Studer neobladder surgery. METHODS: From may 2005 to
      Jan 2008, 25 patients with invasive bladder tumor underwent Studer procedure.
      Among of them, 20 patients were followed up from 6 to 44 months. Functional
      bladder capacity, residual urine, peak flow rate and incontinence in 3, 12, 24,
      36 months following neobladder were evaluated. Surgical associated complications,
      death rate were included as well. RESULTS: There was no significant difference in
      functional bladder capacity, peak flow rate after the procedure (P > 0.05), but
      there was significant difference in residual urine (36 ml vs 80 ml, P < 0.01).
      Hydronephrosis, renal atrophy, urinary infection and hematuria were major
      complications encountered in this study. CONCLUSIONS: The procedure is safe, and
      satisfied urinary function is kept in the neobladder. The long-term outcome will
      be improved with accumulated experiences.

PMID- 19094647
TI  - [Urodynamic analysis of dysuria in female patients].
AB  - OBJECTIVE: To compare the urodynamic diagnostic types of dysuria in female
      patients of different age groups. METHODS: Six hundred and sixteen female
      patients with dysuria were evaluated from March 1997 to July 2008. No patients
      had history of nervous system disease and history of lower urinary tract
      operations. They had detrusor pressure-flow studies and uroflowmetry. The
      urodynamic diagnostic types were analyzed in 3 different age groups. RESULTS: In
      3 groups of 18 - 40 years, 40 - 60 years and > or = 60 years, the diagnosis of
      bladder outlet obstruction (BOO) had the highest proportion (54.8%, 59.1% and
      45.0% respectively). The distribution of detrusor overactivity, detrusor under
      activity and normal function had no significant difference between 3 groups. The
      distribution of BOO and acontractile detrusor had significantly difference
      between 3 groups. When groups of 18 - 40 years and 40 - 60 years were combined
      into 18 - 60 years group and compared with the older group, the proportion of
      BOO, acontractile detrusor and detrusor under-activity showed significantly
      difference. The proportions of BOO in the two groups were 57.3% and 45.0%,
      acontractile detrusor 15.6% and 23.9%, detrusor under-activity 17.4% and 25.0%,
      respectively. The proportion of reduced bladder sensation among detrusor under
      activity patients in the older group was significantly higher. CONCLUSIONS: In
      the urodynamic diagnoses of voiding difficulty in female patients, bladder outlet
      obstruction has the highest proportion. This proportion decreases in the older
      patients. The proportion of acontractile detrusor and detrusor under-activity
      increases in the older group.

PMID- 19094648
TI  - [Morphological study on the role of ICC-like cells in detrusor neuro-modulation
      of rat urinary bladder].
AB  - OBJECTIVE: To investigate the role of ICC-like cells in bladder neuromodulation
      in rat urinary bladder. METHODS: 14 SD rats and 1 guinea pig were sacrificed in
      this study. The ultra structural relationships among interstitial cells, nerves
      and detrusor smooth muscle cells (DSMCs) of urinary bladder were investigated by
      transmission electron microscopy (TEM). c-kit immunofluorescence was used to
      identify ICC-like cells in SD rat urinary bladder and the structural relationship
      between ICC-like cells and nerve terminals was studied by immunofluorescence
      (double-label). RESULTS: Gap junction between ICC-like cells and DSMCs was
      confirmed by TEM. ICC-like cells were very close apposition with nerve terminals
      under TEM. ICC-like cells were identified to exist in sub-urothelium layer, along
      the longitude of smooth muscle bundles and among detrusor smooth muscle in SD rat
      urinary bladder by c-kit immunofluorescence. Double-labeled tissue with c-kit and
      PGP9.5 antibodies also showed that ICC-like cells were very close apposition with
      nerve terminals in SD rat bladder. CONCLUSIONS: Morphological study indicated
      that ICC-like cells in rat urinary bladder may play an important role in detrusor
      neuromodulation. Further study on function will be helpful for elucidating the
      mechanism of bladder neuromodulation clearly.

PMID- 19094651
TI  - [Clinical analysis of post pancreatoduodenectomy hemorrhage].
AB  - OBJECTIVE: To explore the factors of post pancreatoduodenectomy hemorrhage.
      METHODS: The clinical data of 263 cases between January 1998 and April 2008
      underwent pancreatoduodenectomy were analyzed prospectively. RESULTS: The overall
      mortality rate was 4.94% (13/263). Postoperative bleeding occurred in 23 patients
      (8.75%), with 8 episodes ending fatally (34.8%). The tumor size, Child
      classification, caput total resection and pancreatic leakage were identified as
      significant risk factors for post pancreatoduodenectomy hemorrhage by means of
      univariate analysis. The multivariate Logistic regression analysis revealed that
      all of the five factors turned out to be the independent risk factors.
      CONCLUSIONS: The prevention of these bleeding complications depends in the first
      place on meticulous hemostatic technique. The pancreatic leakage is also one of
      the most important factors due to postoperative bleeding. The prophylactic use of
      somatostatin is not necessary.

PMID- 19094652
TI  - [C(2) trans-laminar screws for atlantoaxial instability: preliminary clinical
      report of nine cases].
AB  - OBJECTIVE: C(2) pedicle screw is the classic instrumentation for posterior C(2)
      fixation. But it could be dangerous in case of anatomical variation, such as high
      riding vertebral artery and small C(2) pedicle. C(2) trans-laminar screw could be
      an alternative choice. This retrospective study is to evaluate the feasibility of
      C(2) trans-laminar screw for atlantoaxial instability with anatomical variation.
      METHODS: In our clinical work, we had nine atlantoaxial instability cases with
      C(2) pedicle malformation. If the malformation is unilateral, we inserted one
      C(2) trans-laminar screw and one C(2) pedicle screw in the normal pedicle; if the
      malformation is bilateral, bilateral trans-laminar screws were used. Then C(2)
      instrumentation could be connected with C(1) lateral mass screw or occipital
      screw in cases with C(1) occipitalization. Then atlantoaxial or occipitocervical
      fusion could be done with morselized autogenous cancellous iliac grafts. RESULTS:
      Nine cases had C(2) trans-laminar screw, including 2 atlantoaxial fusion and 7
      occipitocervical fusion. Six cases had unilateral trans-laminar screw and 3 had
      bilateral trans-laminar screw. Radiographs demonstrated all the screws were
      placed satisfactorily except one. There was no neurological deterioration or
      vertebral artery injury. All the cases had an average follow-up of 9 months (4 -
      13 months). All patients attained solid fusion without screw failure. In the 8
      cases with neurological deficit, 3 were excellent, 1 was good, 2 were fair and 2
      had no change. CONCLUSIONS: C(2) trans-laminar screw fixation could provide
      sufficient stability. This technique could be an alternative to standard C(2)
      pedicle screw in cases with pedicle malformation and high riding vertebral
      artery. It is safe and simple in experienced hands.

PMID- 19094653
TI  - [Systematic review of anterior versus posterior surgical treatments of
      thoracolumbar fractures].
AB  - OBJECTIVE: To evaluate the effectiveness of anterior versus posterior surgical
      treatments of thoracolumbar fractures. METHODS: Randomized controlled trials
      (RCTs) and clinical controlled trials (CCTs) were identified from MEDLINE (1966 -
      2006.7), EMBASE (1966 - 2006.7), PubMed (1996 - 2006.7), Cochrane Library (Issue
      2, 2006).We hand-searched Chinese Journal of Orthopedics (from establishment to
      May 2006) and Orthopaedic Journal of China (from establishment to May 2006). RCTs
      and CCTs were included. Data were extracted by two reviewers with designed
      extraction form. RevMan 4.2.8 software was used for data analysis. RESULTS: Two
      RCTs and four prospective clinical trials were included. The combined results
      showed that compare with posterior surgical management, anterior approach in the
      treatment of thoracolumbar fractures proved the less incidence of complications;
      better neurologic recovery and corrected kyphosis angle; more complete and
      reliable decompression of the canal. However, there was not difference between
      the two groups in the general status outcomes. CONCLUSIONS: To compare with
      posterior fixation system, anterior surgical managements in the thoracolumbar
      spinal trauma might be the optimal choices because the lower rates of
      complications and loss of corrected kyphosis angle; better neurologic recovery,
      also. Besides, due to the lack of Evidence-based guidelines for the treatment of
      thoracolumbar spinal injuries, the results which indicated above need further
      study.

PMID- 19094654
TI  - [Preliminary report of surgical treatment of post-traumatic stiff elbow].
AB  - OBJECTIVE: To report the method and result of open arthrolysis of patients who
      suffered from severe post-traumatic elbow stiffness. METHODS: Of the 12 patients,
      there were 9 male and 3 female, average age of 32 years old (16 - 47 years).
      Primary injury included 7 simple fractures, 1 simple dislocation, 2 fracture
      dislocations and 2 soft tissue injury. The averaged time of immobilization after
      injury was 3.3 weeks (0 - 8 weeks). The averaged time between injury and open
      arthrolysis was 6.4 months (1 - 14 months). Before open arthrolysis, the mean arc
      of total motion was 33.8 degrees (0 degrees - 80 degrees ). Three patients
      suffered from forearm rotation deficiency. Posterior approach was used for 4
      patients, medial approach for 2 patients and both medial and lateral approach for
      6 patients. tissues were resected, which hindered the motion of the elbow and
      perform proximal radioulnar joint arthrolysis for some patients. After
      arthrolysis, the arc of elbow motion could reach 0 degrees - 140 degrees , and
      for the patients who suffered from forearm rotation deficiency, pronation 80
      degrees and supination 90 degrees were gotten. Ulnar nerve transposition was not
      a routine. The patients began active and active-assisted elbow and forearm
      movement the first day after operation. Indomethacin was taken the first day
      after open arthrolysis routinely. RESULTS: Twelve patients were followed up for
      14 - 18 months (averaged 15.8 months). At the latest follow-up, the mean arc of
      total motion was 120.8 degrees (100 degrees - 140 degrees ). Nine patients
      recovered the functional arc of 30 degrees - 130 degrees , and 10 patients
      extended to less than 10 degrees , and 4 patients could extend to 0 degrees . As
      for the 3 patients who suffered forearm rotation deficiency, the forearm rotation
      improved. The mean Mayo elbow performance score was 70.4 (50 - 90) before open
      arthrolysis, and 98.8 (85 - 100) after open arthrolysis. No patient was found to
      have signs of heterotopic ossification. CONCLUSIONS: For the treatment of post
      traumatic stiff elbow, with careful open arthrolysis and early active and active
      assisted exercise we can get good results.

PMID- 19094655
TI  - [Surgical treatment of obstructive hypertrophic cardiomyopathy with ventricular
      septal myectomy concomitant mitral valve replacement].
AB  - OBJECTIVE: To summarize the experiences and results of ventricular septal
      myectomy concomitant mitral valve replacement (MVR) for obstructive hypertrophic
      cardiomyopathy (OHCM). METHODS: From January 2000 to June 2007, 22 patients of
      OHCM with moderate or severe mitral regurgitation underwent concomitant
      ventricular septal myectomy concomitant MVR. There were 20 male and 2 female
      patients. The age ranged from 28 to 51 years old with a mean of (36 + or - 5)
      years old. The left ventricular out tract gradient pressure (LVOTGP) was 55 to
      120 mm Hg (1 mm Hg = 0.133 kPa), with a mean of (88.0 + or - 15.8) mm Hg. The
      manifestation of pre-operative UCG, intra-operative transesophageal
      echocardiography (TEE) and post-operative UCG in 10 d, 6 months and 1 year were
      compared and analyzed. RESULTS: One patient died in hospital due to serious
      ventricular arrhythmias. The intra-operative TEE showed that the phenomenon of
      systolic anterior motion (SAM) of mitral valve disappeared in all patients.
      Twenty-one cases were followed-up. The intra-operative TEE and post-operative UCG
      in every period of all 21 cases survived indicated that the mean LVOTGP and
      interventricular septal thickness (IVST) decreased obviously (P < 0.01).
      CONCLUSION: Concomitant ventricular septal myectomy concomitant MVR is an
      effective and safe treatment for OHCM with moderate or severe mitral
      regurgitation, the short and mid-term outcome is excellent.

PMID- 19094656
TI  - [Promotive effect of adipose-derived stem cells on the wound model of human
      epidermal keratinocytes in vitro].
AB  - OBJECTIVE: To investigate the migrating effect of adipose derived stem cells
      (ADSCs) on the wound model of human epidermal keratinocyte (HEKa). METHODS: Rat
      ADSCs (rADSCs) were isolated and cultured (n = 10), rADSCs were direct co
      cultured with HEKa cells in experiment group (experimental group, n = 10). In the
      control groups, rADSCs were indirect co-cultured with HEKa cells in transwell
      chamber (indirect group, n = 8), or HEKa was cultured alone (single group, n =
      8). Then confluent HEKa cells were scraped to establish a wound model under
      invert microscope. After scraped 24, 48, and 72 h, cell numbers of which migrated
      across the edge of the wound was measured, the rate of wound healing was
      calculated by using SigmaScan Pro 5 software, and the proliferating effect of
      rADSCs on HEKa were examined by incorporation of [(3)H] thymidine. RESULTS: The
      cells migrated across the edge of wound after 24 hours in experimental group,
      indirect group, and single group were (9.2 + or - 0.2), (5.0 + or - 0.3), (4.2 +
      or - 0.3), and were (58.5 + or - 0.4), (26.5 + or - 0.3), (20.7 + or - 0.5) 48
      hours after, and were (125.8 + or - 0.4), (43.0 + or - 0.5), (35.6 + or - 0.5)
      cells/HP 72 hours after, respectively; the numbers were all significantly higher
      in experimental group than those in control groups (P < 0.05). The rates of wound
      healing after scraped 72 hours were 61.0% + or - 3.0%, 35.0% + or - 2.5% and 32.0
      + or - 2.1%, the outcome in experimental group was significantly better than in
      the control groups (P < 0.05). And the thymidine feeding displayed the
      proliferation of HEKa in the three groups were (1440 + or - 210), (1050 + or -
      280) and (1130 + or - 390) cpm/10(5) cell, and there was significant difference
      between the experimental and the control groups (P < 0.05). CONCLUSIONS: The
      rADSCs can promote the migration of HEKa by direct contact with it.

PMID- 19094657
TI  - [The relationship between apolipoprotein E genotype and hypertriglyceridemia
      associated recurrent acute pancreatitis].
AB  - OBJECTIVE: To explore the relationship of apolipoprotein E (ApoE) genotype with
      hypertriglyceridemia-associated recurrent acute pancreatitis. METHODS: Taking the
      fasting serum triglyceride (TG) level > or = 2.3 mmol/L as hypertriglyceridemia,
      ApoE genotypes in 115 patients with hypertriglyceridemia-associated recurrent
      acute pancreatitis were assessed by polymerase chain reaction. According to the
      fasting serum TG level, all patients were divided into 3 groups: TG mild
      elevation group (2.3 mmol/L < or = TG < 5.5 mmol/L, Group A), TG moderate
      elevation group (5.5 mmol/L < or = TG < 11.3 mmol/L, Group B), and TG severe
      elevation group (TG > or = 11.3 mmol/L, Group C). RESULTS: Group C had
      significantly fewer patients with biliary tract disease, improper diet and heavy
      alcohol consumption, and significantly more patients with passed history of
      moderate-severe hypertriglyceridemia than Group A and B (P < 0.05). The
      proportion of patients with E3/4, E3/2, E2/4 and E2/2 genotypes and gene
      frequency for epsilon 2 and epsilon 4 alleles are significantly higher in Group C
      than in Group A and B(P < 0.05). Group B had significantly more patients with
      E3/2 genotype and higher gene frequency for epsilon 2 allele than Group A (P <
      0.05). CONCLUSIONS: Apo epsilon 2 and epsilon 4 alleles are closely related to
      moderate-severe hypertriglyceridemia-associated recurrent acute pancreatitis.

PMID- 19094658
TI  - [The influence of tumor cells spreading in blood to relapse and distant
      metastasis of hepatocellular carcinoma after surgery].
AB  - OBJECTIVE: To study the relationship between peripheral blood hepatocellular
      carcinoma cells-associated AFP mRNA and tumor relapse and metastasis. METHODS: To
      detect several blood samples from the HCC patients by nested RT-PCR to find out
      AFP mRNA after 24 h, 72 h and one week and 4 weeks after surgery, and followed up
      the HCC patients for 1, 2, 3 years. RESULTS: There were 7 patients occurred
      relapse or distant metastasis in 12 patients with AFP mRNA positive (7/12,
      58.3%), there were 5 patients occurred relapse in 19 patients with AFP mRNA
      negative (5/19, 26.3%) within 1 year, there was 4 patients occurred relapse in
      second year (9/19, 47.3%); 5 patients occurred relapse in third year (10/19,
      52.6%). Obvious connection between patients AFP mRNA positive and AFP mRNA
      negative was observed (P < 0.01). CONCLUSIONS: HCC with AFP mRNA positive has
      more change to be recurrent compared with HCC patients with AFP mRNA negative.

PMID- 19094670
TI  - [Evaluation of efficacy and safety on steroid withdraw at the seventh day after
      liver transplantation].
AB  - OBJECTIVE: To evaluate efficacy and safety on steroid withdrawal at the seventh
      day after liver transplantation. METHODS: Seventy-six adult patients undergoing
      first cadaveric liver transplantation from October 2005 to October 2007 were
      randomly divided into 7 day (n = 40) and 3 month (n = 36) steroid withdrawal
      groups. All patients received FK506 3 mg and intravenous methylprednisolone 1000
      mg during intra-operation and FK506 thereafter was adjusted to predefined 8 - 12
      microg/L from day 1 to month 6. Patients in 7 day steroid withdrawal group
      received 500, 240, 200, 160, 80, 40 and 20 mg intravenous methylprednisolone
      tapered daily from postoperative day 1 to day 7. In 3 month steroid withdrawal
      group, patients received the same protocol as 7 day steroid withdrawal group for
      intravenous methylprednisolone tapered daily from postoperative day 1 to day 7
      and thereafter received oral prednisone 48, 40, 32, 24, 16, 8, 4 mg tapered every
      3 days and maintained 4 mg to the 3(rd) month. All patients were followed up for
      6 months. The incidence of treated acute rejection and side effects were
      evaluated between two groups. RESULTS: A total of 69 cases were fully followed
      up, and 7 cases were discontinued including death (n = 2), server infection (n =
      2), protocol violation (n = 2) and retransplantation (n = 1). There were no
      statistical difference between 2 groups concerning the incidence of acute
      rejection, hypertension, hyperlipemia and other adverse events (P > 0.05), but
      significant difference in incidence of diabetes (17.5% vs. 38.9%, P = 0.047).
      CONCLUSION: Steroid withdrawal strategy at day 7 is same safety and efficacy as
      steroid withdrawal at 3 month.

PMID- 19094671
TI  - [Establishment of formula predicting adult standard liver volume for liver
      transplantation].
AB  - OBJECTIVE: To establish a favorable formula of estimation adult standard liver
      volume (SLV) based on the data of living donors for liver transplantation.
      METHODS: From March 2005 to December 2007, 90 Adult-to-Adult living donor liver
      transplantation were performed. The donors' anthropometric data of gender, year,
      body weight and body height was collected prospectively. The total liver volume
      (TLV) of 90 living donors was measured by computed tomography. The correlation
      between TLV and several factors including body weight index (BMI) and body
      surface area (BSA) were analyzed. Then multiple stepwise linear regression
      analysis was performed and a new equation predicting SLV to improve approximate
      TLV was determined. TLV was then compared with the estimation standard liver
      volume (ESLV) calculated using our formula and published formulas in literature
      previously. RESULTS: All the subjects had a mean body weight of (62.4 +/- 8.7)
      kg. The mean total liver volume was (1319.1 +/- 167.0) ml. There were positively
      correlated between TLV and body weight (BW), which could be expressed in the
      equation: TLV (ml) = 12.5 x BW (kg) + 536.4 (r(2) = 0.43, P < 0.01). Compared TLV
      with ELSV, which were calculated using previously published formulas based on the
      anthropometric data of the 90 subjects, the difference was be statistically
      significant. CONCLUSION: A new simple formula is established that might be a more
      suitable to calculate TLV in Chinese adults.

PMID- 19094672
TI  - [The cause and management of postoperative venous outflow obstruction after
      orthotopic liver transplantation].
AB  - OBJECTIVE: To investigate the causes and treatment of postoperative venous
      outflow obstruction after orthotopic liver transplantation (OLT). METHODS:
      Clinical data of 776 patients after OLT were analyzed retrospectively between
      January 2000 and December 2006. The accumulated experiences in diagnosis and
      treatment of postoperative outflow obstruction after OLT were reviewed. RESULTS:
      Venous outflow obstruction occurred in 10 patients (1.29%) after OLT, among those
      6 had supra-hepatic inferior vena cava (IVC) stenosis, 2 had IVC stenosis of the
      post-hepatic segment, and 2 had outflow obstruction of hepatic vein. The
      diagnosis was confirmed by inferior vena cavography in all the patients. Of the
      10 patients, 8 received percutaneous transluminal angioplasty (PTA) or metallic
      stent replacement, and 2 underwent liver retransplantation (re-LT) when
      interventional therapy failed. Three patients died from outflow obstruction, so
      the outflow obstruction related mortality was 30% in the patients. CONCLUSIONS:
      Complications of outflow obstruction after OLT were associated with surgical
      technique like vascular anastomosis, various types of cavo-caval anastomosis and
      graft size mismatch between donor and recipient. Making an early diagnosis and
      giving timely treatment including interventional therapy or re-LT is the key to
      improve the prognosis of outflow obstruction.

PMID- 19094673
TI  - [Effect of the amount of portal blood stasis removal on endotoxemia and liver
      function after liver transplantation].
AB  - OBJECTIVE: To investigate the influence of the amount of portal blood stasis
      removal on endotoxemia and liver function after liver transplantation. METHODS:
      Forty-seven patients who received liver transplantation from February 2006 to
      November 2007 were divided into 2 groups according to the amount of portal blood
      stasis removal during operation: group A (n = 26) 50 ml and group B (n = 21) 200
      ml of portal blood stasis removal respectively. The levels of plasma endotoxin, D
      lactate, tumor necrosis factor-alpha, interleukin-6, liver function and blood
      coagulation were examined and analyzed. RESULTS: Under the condition of no
      significant difference in sex, age, primary liver diseases and Child-pugh's
      classification, cold ischemic time, total operation and anhepatic time, operation
      methods, volume of blood loss and transfusion, and all preoperative observations.
      Most of observations showed the restoration of the patients in group B was better
      than that in group A. The plasma levels of endotoxin, D-lactate, tumor necrosis
      factor-alpha, interleukin-6, alanine aminotransferase, aspartate
      aminotransferase, prothrombin time and activated partial thromboplastin time in
      group B were significantly lower than those in group A (P < 0.05). The level of
      plasma prealbumin in group B was significantly higher than that in group A (P <
      0.05). CONCLUSIONS: The removal of 200 ml portal blood stasis leads to a better
      results than that of 50 ml, and it can help alleviate endotoxemia and facilitate
      the restoration of the liver function after liver transplantation.

PMID- 19094674
TI  - [The change of intestinal microecology in rats after orthotopic liver
      transplantation].
AB  - OBJECTIVE: To investigate the intestinal microflora status and bacterial
      translocation in rats after liver transplantation. METHODS: Male Brown-Norway
      (BN) rats were randomly divided into 4 groups: group I (n = 8) for liver
      transplantation; group II (n = 8) for simulated liver transplantation; group III
      (n = 8) for sham operation and group IV (n = 8) for normal group. Caecal
      bacterial counts, plasma endotoxin, intestinal mucosal ultrastructure and
      bacterial translocation to liver, spleen, kidney, and mesenteric lymph node were
      studied 24 h after surgery. RESULTS: The numbers of Bifidobacterium and
      Lactobacillus per gram of wet feces were significantly decreased in group I
      compare with those in the group III and group IV, while Enterobacteriaceae and
      Enterococcus counts were increased markedly compare with those in the group III
      and group IV, but no different was found between group I and group II. Impaired
      intestinal mucosa integrity were found in the group I and group II. In group I,
      the levels of plasma endotoxin increased after the transplantation when compare
      with group III and group IV. Increased incidence of bacterial translocation to
      liver, spleen and mesenteric lymph node were also observed after the
      transplantation (compare with those in the group IV, P < 0.01; compare with those
      in the group III, P < 0.01, P < 0.01, P < 0.05, separately). The increased rate
      of the bacterial translocation in liver was also found in transplantation group
      as compare with group II (P < 0.05). CONCLUSIONS: Liver transplantation may lead
      to disturbance of intestinal microflora and impairment of intestinal mucosal
      barrier function, and this dysfunction might be caused by the process of
      intestinal ischemia-reperfusion injury in transplantation.

PMID- 19094677
TI  - [Management of difficult, severe and recurrent Budd-Chiari syndrome].
AB  - OBJECTIVE: To investigate the management of complicated, severe or recurrent Budd
      Chiari syndrome. METHODS: From February 2004 to August 2007, 28 patients with
      complicated, severe or recurrent Budd-Chiari syndrome were treated. In this
      series, 16 patients relapsed after treated with percutaneous transluminal
      angioplasty or stent deployment, 2 cases relapsed after surgery; and the other 10
      were under severe conditions and hard to treat, including malignancy of the
      inferior vena cava and right atrium. Meso-cavo-atrial shunt was carried out in 10
      cases, meso-cavo-jugular shunt in 6 (capitis medusa was used in one case),
      cavoatrial shunt in 2 and cavo-jugular shunt in 1, mesocaval shunt in 2, and
      radical or extended radical correction in 7. RESULTS: One patient (3.6%) died in
      24 hours after operation. Graft infection occurred in 1 case. Excellent, good,
      fair, poor and death rate were 22.2%, 55.5%, 14.8%, 3.7% and 3.7%, respectively,
      the overall effective rate was 92.5%. CONCLUSION: To select personalized
      treatment according to the disease status brings hopes to difficult, severe,
      recurrent Budd-Chiari syndrome.

PMID- 19094678
TI  - [Clinical questionnaires about benign prostatic hyperplasia].
AB  - OBJECTIVE: s To assess the understanding degree of urologists for benign
      prostatic hyperplasia (BPH) and the clinical characteristics of BPH patients.
      METHODS: The questionnaires was distributed to urologists and patients in 119
      hospitals over the country, respectively. The urologist survey was mainly focused
      on the questions of BPH progression and therapeutic model. The patient survey was
      mainly focused on the questions of patient's age, symptom features and the
      preference to receiving treatment. RESULTS: The evaluations based on 289
      completed urologist questionnaires and 4253 completed patient questionnaires
      showed that 98.6% of urologists agreed that BPH was a progressive disease but
      there were still some differences in understanding the risk factors for BPH
      progression. Additionally, 98.1% of patients were diagnosed to be moderate or
      severe BPH, nocturia was the most frequent symptom. In the treatment for BPH,
      both the urologists and patients concerned about how to improve the system
      rapidly. CONCLUSIONS: This study is the first questionnaires specifically to the
      urologists and BPH patients, the results would reflect the situations of BPH
      diagnosis and treatment in China and would be helpful to the development of BPH
      guideline.

PMID- 19094679
TI  - [Applying bladder outlet obstruction number to predict bladder outlet obstruction
      of benign prostatic hyperplasia].
AB  - OBJECTIVE: Applying bladder outlet obstruction number (BOON) to predict bladder
      outlet obstruction (BOO) of benign prostatic hyperplasia (BPH). METHODS: Seventy
      six male who were suspected to suffer from BOO due to BPH with lower urinary
      tract symptoms were evaluated. The data included prostate volume (by transrectal
      prostate ultrasound), maximum urine flow rate (Qmax) and mean voided volume to
      calculate the BOON by simple algorithm: prostate volume (cm(3))-3 x Qmax (ml/s)
      0.2 x mean voided volume (ml). Pressure-flow study was also performed on each
      patient to get AG number and Schafer obstruction grade. Correlation between
      traditional parameters, BOON and AG number was calculated to evaluate the price
      of using BOON to predict BOO. RESULTS: Parameters such as age, prostate volume,
      maximum urine flow rate, residual urine and BOON were used as independent and AG
      was used as dependent to calculated the multiple linear regression. Data
      expressed the entire regression equation's R = 0.542 (P = 0.000), and result
      showed BOON had the strongest relationship with AG (P = 0.000). Eighteen
      patients' BOON number were greater than -10, by AG number and Schafer obstruction
      grade proving, all these patients were suffered from BOO, the sensitivity and the
      specificity of judging BOO by BOON were 31% and 100% respectively. While take
      BOON as -20, the sensitivity and the specificity were 42.4% and 88.2%, when take
      BOON as -30, the sensitivity and the specificity were 66.1% and 82.4%,
      respectively. Fifty-two persons' BOON were greater than -40, 46 patients suffered
      from BOO, the sensitivity and the specificity were 77.9% and 64.7%, the
      specificity and the opportunity of having BOO decreased significantly. The data
      showed that: taking BOON = -30 as critical point can predict BOO with higher
      sensitivity and specificity, greater BOON means greater possibility of BOO.
      CONCLUSIONS: Using BOON which is deduced from prostate volume, maximum urine flow
      rate and mean voided volume, the point -30 as critical point, can predict the
      probability of BOO with higher sensitivity and specificity.

PMID- 19094681
TI  - [Classification of the pectus excavatum and minimally invasive Nuss procedure].
AB  - OBJECTIVE: To investigate the improvement of the Nuss procedure with the
      classification of the pectus excavatum by symmetry and extend the indication of
      the operation for a better outcome. METHODS: The clinic data of 403 patients who
      underwent repair of pectus excavatum by Nuss technique and its modifications from
      July 2002 to September 2007 were reviewed retrospectively. There were 299 male
      patients and 104 female patients. The age ranged from 2 years and seven months
      old to 32 years old, with a mean of (8.0 +/- 5.1) years old. The entire group of
      the CT index ranged from 3.25 to 51.20, with a mean of (5.0 +/- 3.0). According
      to the morphology of the pectus and practically the bar shaping, Park's
      classification was simplified to symmetric type, eccentric type, and unbalanced
      type. The patients of symmetric type were all received original Nuss procedure,
      and the other two types underwent the procedure using characteristic bar shaping
      and technical modification. RESULTS: Among the 403 patients, 257 patients (63.8%)
      were symmetric pectus excavatum, and 48 patients (11.9%) were eccentric, other 98
      patients (24.3%) were unbalanced type. All the patients underwent the procedure
      successfully. The total time of the procedure ranged from 30 to 165 min, with a
      mean of (45.7 +/- 12.6) min. Volume of blood loss during the operation ranged
      from 1 to 80 ml, with a mean of (4.8 +/- 6.2) ml. The days of hospitalization
      ranged from 4 to 12 d, with a mean of (7.1 +/- 1.0) d. The duration of following
      up ranged from 1 month to 5 years, and the results of the repair were excellent
      in 391 patients (97.0%). Five patients received a further operation, including 1
      patient of recurrent pectus excavatum caused by bar displacement, 4 patients of
      protruding side way. There were 23 patients of complications for an overall
      complication rate of 5.7%. And the other 18 patients of complications included 2
      patients of pericardium perforation, 2 patients of bar displacements caused
      intercostal dilaceration, 2 patients of diaphragmatic muscle injuries, 1 patient
      of hemothorax, 8 patients of pneumothorax, 2 patients of intermittent pains for 2
      months, 1 patient of scoliosis caused by persistent pain. CONCLUSION: To classify
      the pectus excavatum with symmetry and to choose different ways of procedure can
      extend the indication of Nuss procedure and receive a better outcome.

PMID- 19094682
TI  - [Create a standard mini-swine model of chronic ischemic myocardium by
      thoracoscopy].
AB  - OBJECTIVE: To create a standard mini-swine model of chronic ischemic myocardium
      by endoscopy for the research of gene transfer and stem cell. METHODS: Twenty
      three male China experimental minipigs were used, aged from 8 to 11 months with a
      mean of (9.3 +/- 1.8) months and weighed from 20 to 30 kg with a mean of (29.3 +/
      4.3) kg. The myocardial ischemia was established by gradual occlusion of the
      left circumflex coronary artery (LCX) with an Ameroid constrictor. The Ameroid
      constrictor was implanted around LCX by endoscopy. Selective coronary
      angiography, electrocardiogram and Echo-Doppler study were performed
      perioperatively to evaluate the degree of stenosis. RESULTS: Chronic ischemic
      myocardial models were successfully generated in 20 of 23 swine by full
      endoscopy. Ameroid constrictors were placed at the LCX accurately. Three swine
      died of anesthetic accident, cardiac arrhythmia at secondary coronary
      angiography, and pulmonary infection within 6 weeks after operation respectively.
      Operation time was 25 to 65 min with a mean of (46 +/- 9) min. The blood loss was
      30 to 60 ml with a mean of (55 +/- 12) ml. Six weeks later, coronary angiography
      revealed the total occlusion and partial stenosis (> 85%) of the LCX occurred in
      7 and 13 swine respectively. Cardiac systolic and diastolic dysfunction were
      found in all swine. The ejection fraction value was (65.0 +/- 6.3)% before
      operation and (41.0 +/- 9.3)% after operation (P = 0.008). The fractional
      shortening value was (36.2 +/- 4.3)% before operation and (34.2 +/- 2.3)% after
      operation (P = 0.027). CONCLUSION: The endoscopic surgery is a less invasive way
      to create a standard mini-swine model of chronic ischemic myocardium with
      effective results.

PMID- 19094683
TI  - [Prognostic factors for 72 patients with osteosarcoma of the extremity treated
      with neoadjuvant chemotherapy].
AB  - OBJECTIVE: To determine the prognostic factors that influence survival of
      patients with non-metastatic, high-grade osteosarcoma of the extremities.
      METHODS: The data of 72 patients treated between June 2003 and June 2007, was
      retrospectively evaluated in relation to many factors including gender, age, etc.
      RESULTS: Tumor necrosis was significantly related to gender, tumor volume change,
      tumor margin and T2 signal intensity of the extraosseous component of bone
      sarcomas. Multivariate analysis, tumor necrosis was only related to tumor volume
      change. Upon multivariate analysis, good histologic response was related to the
      outcome of patients. CONCLUSIONS: Event free survival is related to the tumor
      necrosis, the level of alkaline phosphatase and the change of T2 signal of the
      extraosseous component. Tumor necrosis is related to the volume change after
      preoperative chemotherapy. These factors must be considered when deciding risk
      adapted treatments for patients with osteosarcoma.

PMID- 19094684
TI  - [Measuring blood flow change of osteonecrosis of femoral head with laser doppler
      flowmetry].
AB  - OBJECTIVE: To detect the blood perfusion of the necrotic area and the femoral
      head and neck junction in the patients diagnosed as osteonecrosis of femoral head
      (ONFH) with laser doppler flowmetry (LDF). METHODS: From 2007 to 2008, 50
      patients with ONFH 82 hips were performed core decompression and autologous stem
      cells transplantation. Group A was for ARCO stage II 46 hips (IIA 6 hips, IIB 22
      hips, IIC 18 hips), and Group B was for stage III 36 hips (IIIA 20 hips, IIIB 10
      hips, IIIC 6 hips). Blood perfusion of necrotic area and femoral head and neck
      junction with LDP were detected during the operation. Statistical analysis was
      made. RESULTS: In Group A, the perfusion volume of necrotic area was (30.2 +/-
      3.0) PU, and the perfusion volume of femoral head and neck junction was (103.4 +/
      4.4) PU. In Group B, the perfusion volume of necrotic area was (30.6 +/- 2.8)
      PU, and the perfusion volume of femoral head and neck junction was (103.4 +/-
      3.9) PU. In Group A and Group B, the perfusion volume of necrotic area was lower
      than that of femoral head and neck junction, and the difference was significant
      (P < 0.01). CONCLUSIONS: LDF can effectively detect that the perfusion volume of
      ONFH decreased, which provides a theoretical basis in order to further study the
      pathogenesis of ONFH. Meanwhile, there is application value of LDF on the study
      of ONFH.

PMID- 19094685
TI  - [Comparison of clinicopathological features and operative prognosis of gastric
      carcinoma complicated with Krukenberg tumor and with pelvic peritoneal
      dissemination].
AB  - OBJECTIVE: To compare the clinicopathological characters and operative prognosis
      of gastric cancer complicated with Krukenberg tumor and with pelvic peritoneal
      dissemination. METHODS: Thirty-nine female cases of gastric carcinoma with pelvic
      metastasis were treated operated on between August 1994 and March 2006. Among
      them, 18 cases were complicated with Krukenberg tumor and 21 cases with pelvic
      peritoneal dissemination. The clinicopathological characters in the two groups
      were recorded and compared and the operative prognosis were analyzed. RESULTS:
      There was no significant difference in age, tumor location and size, hepatic
      metastasis, organic encroachment, infiltration degree, positive lymph nodes,
      differentiated degree, tissue typing, Borrmann typing, value of carcinoembryonic
      antigen between the two groups (P > 0.05). The rate of P3 (peritoneal
      dissemination) in the cases of Krukenberg tumor (44.4%) was significantly lower
      than that in pelvic peritoneal dissemination group (85.7%) (P < 0.01), whereas
      the focal resection rate (77.8%) and multi-organ dissection rate (55.6%) were
      significantly higher than in pelvic peritoneal dissemination (38.0%, 23.8%) (P <
      0.05). The mean survival of all cases was 12.6 months. The mean survival in the
      patients with Krukenberg tumor and pelvic peritoneal dissemination was 20.5, 15.0
      months, respectively (P < 0.05). The mean survival of total focal resection,
      palliative focal resection, non-focal resection was 19.9, 12.5 and 5.7 months,
      respectively (P < 0.01). Non-focal resection, pelvic peritoneal dissemination, P3
      of peritoneal implantation, hepatic metastasis, organic encroachment, total
      gastric cancer were unfavorable prognosis factors for all cases. CONCLUSIONS:
      Compared with pelvic peritoneal dissemination, the gastric cancer with Krukenberg
      tumor is associated with more limited peritoneal dissemination, higher resection
      rate and better prognosis. Focal resection can improve the prognosis.

PMID- 19094686
TI  - [Biomechanical effect of the iliac screw insertion depth on lumbo-iliac fixation
      construct].
AB  - OBJECTIVE: To biomechanically compare the stability of the short and long iliac
      screw fixation constructs in lumbo-iliac reconstruction. METHODS: Seven adult
      human embalmed cadavers (L(3)-pelvis) were used. Using posterior spinal fixation
      system, L(4)-S(1) pedicle screw fixation was performed. This was defined as
      intact state of the sacroiliac joint. After the intact test, total sacrum
      resection and L(4)-L(5)-pelvis reconstruction by pedicle screw and iliac screw
      with different lengths were performed as follow: short screw group (as the length
      of exceeding 2 mm over ischial notch) and long screw group (as the length of
      exceeding 2 mm over anterior inferior iliac spine). Using the 858 MTS material
      testing machine, biomechanical testing was performed under 800 N compression and
      7 Nm torsion loading modes. At last, the axial pullout test of two iliac screws
      was executed. Construct stiffness in compression and torsion test, and maximum
      pullout force were analyzed. RESULTS: Insertion lengths of the short and long
      iliac screw were (70 +/- 2) mm and (138 +/- 4) mm respectively. The lumbo-pelvic
      reconstruction using short and long iliac screw, respectively restored 53.3% +/-
      13.6% and 57.6% +/- 16.2% of the initial stiffness in compression testing, and
      respectively harvested 55.1% +/- 11.9% and 62.5% +/- 9.2% of the initial
      stiffness in torsion testing. No significant difference was detected between the
      two reconstructions (P > 0.05), however, the compressive and torsional stiffness
      of the two techniques were markedly less than the intact condition (P < 0.05).
      The maximum pullout strength of long iliac screw was significantly higher than
      short screw (P < 0.05). CONCLUSIONS: Under the physical loading, lumbo-pelvic
      fixation construct using the short iliac screw may obtain mechanical stability
      comparable to that by long iliac screw. The short iliac screw is only the half of
      the long iliac screw by length, could reduce the implantation risk. However, the
      long iliac screw behaves greater axial pullout force, should be applied as far as
      possible in the osteoporosis patient. The lumbo-pelvic reconstruction utilizing
      any length of iliac screw is difficult to restore the local stability.

PMID- 19094687
TI  - [Vitamin D receptor gene polymorphisms: no association with low bone mineral
      density in adolescent idiopathic scoliosis girls].
AB  - OBJECTIVE: To investigate the association of vitamin D receptor (VDR) gene
      polymorphisms with low bone mineral density (BMD) in adolescent idiopathic
      scoliosis (AIS) girls. METHODS: Blood samples were obtained from 146 AIS girls
      and 146 healthy girls. Anthropometric parameters of AIS group including age, body
      height, weight and Cobb angle were all recorded. Polymerase chain reaction
      restriction fragment length polymorphism (PCR-RFLP) technique was used to detect
      and analyze VDR gene distributions of AIS group and control group. BMD of the
      lumbar spine (L(1)-L(4)) and proximal femur were measured using dual energy x-ray
      absorptiometry in AIS group. RESULTS: The frequency of Bb genotype was
      significantly higher in patients than that in controls (P < 0.05). There was no
      distinction among the lumbar spine and proximal femur BMD of each genotype in AIS
      group (P > 0.05). CONCLUSION: VDR gene polymorphisms have no association with the
      low spine lumbar and proximal femur BMD in AIS girls.

PMID- 19094695
TI  - ?

PMID- 19094694
TI  - ?

PMID- 19094698
TI  - ?

PMID- 19094696
TI  - ?

PMID- 19094697
TI  - ?

PMID- 19094700
TI  - ?

PMID- 19094699
TI  - ?

PMID- 19094703
TI  - ?

PMID- 19094702
TI  - ?

PMID- 19094701
TI  - ?

PMID- 19094704
TI  - [Clinicopathologic features and molecular genetic analysis of multilocular cystic
      renal cell carcinoma].
AB  - OBJECTIVE: To assess the clinicopathological features and molecular genetic
      changes of multilocular cystic renal cell carcinoma (MCRCC). METHODS: All the
      data reviewed were from the files of pathology department of Changhai hospital
      collected from 1990 to 2006. In totally 706 cases of renal cell carcinoma
      studied, there were 21 MCRCC cases identified. The clinical and pathological
      features were assessed, immunohistochemical staining was performed, and loss of
      heterozygosity (LOH) and microsatellite instability (MSI) were assessed using
      four microsatellite markers on chromosomes 3, 9 and 14. RESULTS: Of the 21
      patients, the age ranged from 34 to 72 years (mean 50 years), 19 were male and
      two female. Tumors were found incidentally in 18 patients during physical
      examination, three patients had anemia or microhematuria. Among the 21 patients,
      10 tumors were in the left kidney and 11 in the right. Eighteen patients were
      stage T1, two stage T2, and one stage T3 with perinephric tissue involvement.
      Follow up information was available in 20 patients, all showed no evidence of
      tumor recurrence or metastasis. Grossly, the tumor size ranged from 0.3 cm to
      10.0 cm in the greatest dimension, consisting of multilocular cysts with variable
      sizes which contained light yellow, colloid or hemorrhagic fluid. The septae
      varied in thickness (ranged 0.1 cm to 0.5 cm, mean 0.2 cm). Microscopically the
      cysts were lined by single to multilayered epithelial cells with clear or lightly
      eosinophilic cytoplasm. There were clusters of clear cells seen in the septae
      stroma. Sixteen tumors were of Fuhrman grade 1, and five were of Fuhrman grade 2.
      Immunohistochemically, the clear cells were positive for vimentin, ABC, CAM5.2
      and EMA. Six samples were positive for CD10, and 16 were positive for NSE. Among
      21 patients, PCR amplification was successful in 11 patients. Microsatellite
      alterations were found in five patients. LOH was observed in 3 of 11 MCRCC (27%),
      two were at D3S1560 locus, and one at D14S617 locus. MSI frequency was identified
      in 2 of 11 MCRCC (18%), locating at D9S168 or D14S617 locus, respectively.
      CONCLUSIONS: MCRCC is an uncommon tumor of kidney, constituting 2.9% of all RCC
      enrolled into the study. It has distinctive clinical and pathological
      characteristics with an excellent outcome. Results indicated that MCRCC is a rare
      entity with low malignant potential.

PMID- 19094705
TI  - [Study on clinicopathologic features and immunophenotype of 114 cases of renal
      cell carcinoma].
AB  - OBJECTIVE: To study the clinicopathologic features and immunophenotype of renal
      cell carcinomas, and to discuss their diagnostic value. METHODS: The
      clinicopathologic features of 114 cases of renal cell carcinoma were reviewed and
      categorized on the basis of 2004 WHO classification. Immunohistochemical study
      for a panel of antibodies (including CK, CD10, vimentin, CD117, AMACR, CK7 and
      TFE3) was carried out. The follow-up data, if available, were also analyzed.
      RESULTS: The cases were reclassified into 5 subtypes, including 77 cases (67.5%)
      of clear cell carcinoma (CCRCC), 11 cases (9.6%) of papillary renal cell
      carcinoma (PRCC), 14 cases (12.3%) of chromophobe renal cell carcinoma (chrRCC),
      10 cases (8.8%) of renal carcinoma associated with Xp11.2 translocations/TFE3
      gene fusions (Xp11.2RCC) and 2 cases (1.8%) of unclassified renal cell carcinoma
      (unRCC). Immunohistochemical study showed that the expression rates of CK, CD10
      and vimentin in CCRCC were 93.5% (72/77), 93.5% (72/77) and 75.3% (58/77),
      respectively. On the other hand, all the 11 cases of PRCC studied were positive
      for AMACR. The expression rate of CD117 in chrRCC was 78.5% (11/14). In the 10
      cases of Xp11.2 RCC studied, the expression rates of TFE3, AMACR, CD10 and CK
      were 100% (10/10), 100% (10/10), 90% (9/10) and 70% (7/10), respectively.
      CONCLUSIONS: The various subtypes of renal cell carcinomas are heterogeneous in
      histologic appearance and demonstrate distinctive immunophenotype. The
      expressions of CD10, vimentin, CD117, AMACR, CK7 and TFE3 are helpful in the
      differential diagnosis.

PMID- 19094706
TI  - [Fluorescence in-situ hybrydization detection of 18q21 LOH in human pancreatic
      ductal carcinoma and chronic pancreatitis].
AB  - OBJECTIVE: To investigate 18q21 LOH in human pancreatic ductal adenocarcinomas
      and chronic pancreatitis by fluorescence in-situ hybrydization (FISH) technique,
      and to analyze the relationship between 18q21 LOH and clinicopathologic
      characteristics. METHODS: RP11-729G3 and RP11-850A17, the regions on 18q21, were
      selected as the target fragments, the region RP11-621L6, close to the centromere
      of chromosome 18, was selected as the reference fragment. The specific BAC clones
      were used to isolate and purify the corresponding genomic DNA, which were labeled
      with biotin or DIG by nick translation into dual color probes. 18q21 LOH was
      assessed by dual-color FISH in 30 cases of pancreatic ductal adenocarcinoma and
      10 cases of chronic pancreatitis. All samples were 10% formalin fixed and
      paraffin embedded. The relationship between 18q21 LOH and clinicopathologic
      characteristics was analyzed. RESULTS: Among 30 cases of pancreatic ductal
      adenocarcinoma, 25 cases showed LOH at the region RP11-729G3 (83.3%), and 26
      cases showed LOH at the region RP11-850A17 (86.6%). Among these, 25 cases with
      LOH at both regions, 1 case showed LOH only at the region of RP11-850A17. No LOH
      was found in 10 cases of chronic pancreatitis. CONCLUSIONS: 18q21 LOH is a high
      frequency event in human pancreatic ductal adenocarcinomas. LOH at the regions
      RP11-729G3 and RP11-850A17 demonstrates a high concordance. 18q21 may play an
      important role during pancreatic carcinogenesis and tumor progression. 18q21 LOH
      may be used as a diagnostic marker for pancreatic ductal adenocarcinoma.

PMID- 19094707
TI  - [Clinicopathologic study of pulmonary adenocarcinoma with features of
      bronchioloalveolar carcinoma].
AB  - OBJECTIVE: Further investigation on the incidence and clinicopathologic features
      of bronchioloalveolar carcinomas (BAC) including: (1) BAC of strictly defined,
      (2) adenocarcinoma with bronchioloalveolar features, (3) other different
      histologic subtypes of lung adenocarcinomas. METHODS: Surgical specimens from 348
      lung adenocarcinoma patients admitted in that hospital between 1998 - 2005 were
      included. And clinical data were collected at the same time. Patients of strictly
      defined BAC, BAC with focal invasion (BWFI), and adenomas with bronchioloalveolar
      features (AWBF) were followed-up. Data were analyzed using SPSS statistics
      software and Kaplan-Meier survival curves were constructed. RESULTS: The resected
      lung adenocarcinomas consisted of different histologic subtypes. The most
      frequent one was adenocarcinoma of mixed subtypes (78.2%, 272/348), followed by
      the acinar type (8.1%, 28/348), the papillary type (4.0%, 14/348), the BAC (3.7%,
      13/348), the mucinous (colloid) type (3.4%, 12/348) and the solid types (2.3%,
      8/348). The fetal adenocarcinoma was the least component detected. There was no
      significant difference on the survival curves between groups BAC and BWFI. The
      survival rate of patients with AWBF was poorer than that of BAC and BWFI.
      CONCLUSIONS: Since patients with strictly defined (simple) BAC, BWFI, and AWBF
      have their own distinct clinicopathologic features and prognosis respectively,
      they should be strictly distinguished from other types of pulmonary
      adenocarcinomas.

PMID- 19094708
TI  - [Clinicopathologic characteristics of breast cancer with basal-like
      immunophenotype].
AB  - OBJECTIVE: To study the clinicopathologic characteristics of basal-like
      immunophenotype breast cancer (BLBC). METHODS: 458 cases of female infiltrative
      breast cancer were studied using immunohistochemical staining with an antibody
      panel of ER, PR, HER2, Ki-67, CK5/6, CK14 and epidermal growth factor receptor
      (EGFR) and were classified basing on the immunophenotypes. The clinicopathologic
      characteristics were compared with other immunophenotypes of breast cancer. 228
      of 458 cases of breast cancer were followed up. RESULTS: 46 cases of BLBC were
      screened out among the 458 breast cancers. And histological features of BLBC were
      analysed including the larger diameter of cancer foci (average 3.3 cm),
      appearance of squeezing phenomenon of neighboring cell borders (58.7%, 27/46),
      geography-like distribution of necrosis (52.2%, 24/46), central zone fibrosis
      (30.4%, 14/46) and lymphoplasmacytic infiltration at the margin and stroma
      (63.0%, 29/46). There were nuclear pleomorphism with numerous mitoses. The cancer
      cells were closely arranged, forming irregular solid architectures. There was a
      high expression (> 25%) of Ki-67 (43.5%, 20/46). CK5/6, CK14 and EGFR were
      positive in 58.7% (27/46), 43.5% (20/46) and 65.2% (30/46) respectively. 3-year
      survival rate of BLBC was 66.9%, lower than the luminal A breast cancer and
      similar to HER2 over-expression breast cancer. CONCLUSIONS: The proportion of
      BLBC in the group of breast cancers is 10%. BLBC has its distinct histological
      and cytological features. Currently, it is still necessary to depend on
      immunophenotyping in making a BLBC diagnosis. BLBC is the one of breast cancer
      subtypes with the poorest prognosis.

PMID- 19094709
TI  - [Expression of mucin glycoproteins and cytokeratins in intrahepatic
      cholangiocarcinoma].
AB  - OBJECTIVE: To compare the immunoprofiles of intrahepatic cholangiocarcinoma and
      metastatic colorectal adenocarcinoma for mucin glycoproteins (including MUC1,
      MUC2, MUC5AC and MUC6) and cytokeratins (including CK7, CK19 and CK20), and to
      assess their diagnostic value. METHODS: One hundred cases of intrahepatic
      cholangiocarcinoma and 21 cases of metastatic colorectal adenocarcinoma were
      enrolled into the study. Immunohistochemical study for MUC1, MUC2, MUC5AC, MUC6,
      CK7, CK19 and CK20 was carried out in all cases by EnVision method. RESULTS: In
      intrahepatic cholangiocarcinoma, the expression rates of MUC1, MUC2, MUC5AC and
      MUC6 were 61.0%, 2.0%, 22.0% and 8.0% respectively, as compared to 57.1%, 47.6%,
      19.0% and 23.8% respectively in metastatic colorectal adenocarcinoma. On the
      other hand, the expression rates of CK7, CK19 and CK20 in intrahepatic
      cholangiocarcinoma were 73.0%, 53.0% and 15.0% respectively, in contrast to
      14.3%, 90.5% and 85.7% respectively in metastatic colorectal adenocarcinoma. The
      difference in expressions of MUC2, MUC6, CK7 and CK20 carried statistical
      significance. CONCLUSIONS: The immunoprofile for mucin glycoproteins and
      cytokeratins provides important clues in distinguishing between intrahepatic
      cholangiocarcinoma and metastatic colorectal adenocarcinoma to liver. The
      immunophenotype of MUC2-/MUC6-/CK7+/CK20- indicates the diagnosis of intrahepatic
      cholangiocarcinoma, while MUC2+/MUC6+/CK7-/CK20+ suggests the possibility of
      metastatic colorectal adenocarcinoma.

PMID- 19094710
TI  - [Effect of tissue factor pathway inhibitor on apoptosis of rat mesangial cells
      and Fas and bcl-2 expression].
AB  - OBJECTIVE: To study the biological impact and mechanism of recombinant tissue
      factor pathway inhibitor (rTFPI) on apoptosis of rat kidney mesangial cells
      (MsC). METHODS: TFPI expression in human glomerular minor lesion (GML), mesangial
      proliferative glomerulonephritis (MPGN) and cultured rat MsC was detected using
      immunohistochemistry and immunofluorescence, respectively. Rat MsC were incubated
      with rTFPI and its variant peptides. Morphological changes of apoptosis were
      investigated by Hoechst 33258 and the apoptotic rate was assessed by flow
      cytometry. DNA fragmentation and effect of rTFPI on expression of caspase-3, Fas
      and bcl-2 were studied using gel electrophoresis and Western blot respectively.
      RESULTS: The expression of TFPI in MPGN was higher than that in GML. TFPI was
      expressed in cultured rat mesangial cells. Apoptosis of MsC was induced by rTFPI,
      especially by its C-termianl, in a dose- and time-dependent manner. Apoptosis
      ratios of MsC treated with rTFPI were 2.1, 3.0 and 4.9 times more than control,
      respectively. Expression of gene caspase-3 and Fas was up-regulated in a dose
      dependent manner wherease bcl-2 expression did not show any changes. CONCLUSION:
      rTFPI induces apoptosis in cultured rat mesangial cells by its C-terminal
      possibly via Fas/FasL pathway.

PMID- 19094712
TI  - [Paraganglioma-like meningioma: report of four cases with ultrastructural and
      immunohistochemical studies].

PMID- 19094711
TI  - [Effect of ryanodine receptor 2 gene silencing on ischemia-reperfusion injury of
      rat myocardial cells].
AB  - OBJECTIVES: To block the synthesis of ryanodine receptor 2 (RyR2) in myocardial
      cells by RNA interference and to investigate its biological impact on ischemia
      reperfusion (I/R) in rat myocardial cells. METHODS: Rat myocardial cells were
      isolated and cultured for an I/R model in vitro. RNA interference technique was
      used to block the synthesis of RyR2 in myocardial cells. Changes of LDH level,
      apoptosis, RyR2 mRNA expression and cytosolic Ca(2+) concentration were analyzed
      accordingly. RESULTS: Myocardial cells after I/R manipolation were severely
      injuried (LDH leakage, 125 IU/L vs 12 IU/L, P < 0.05), apoptosis (60.1% vs 5.5%,
      P < 0.05), significant cytosolic Ca(2+) overload (21.2 vs 7.6, P < 0.05) and
      remarkable mitochondrial membrane potential loss (37.2 vs 85.1, P < 0.05).
      However, no visible change of RyR2 was observed (20.1 vs 22.7, P > 0.05). Pre
      treatment with RyR2 specified siRNA demonstrated suppressed expression of RyR2
      (6.8 vs 20.1, P < 0.05), increased mitochondrial membrane potential (55.8 vs
      37.2, P < 0.05), attenuated cytosolic Ca(2+) overload (8.6 vs 21.2) and cellular
      apoptosis (31.2% vs 60.1%, P < 0.05). CONCLUSION: RyR2 gene silencing enables to
      protect myocardial cells from I/R injury in vitro.

PMID- 19094713
TI  - [Complement C4d and pathologic diagnosis of antibody-mediated renal allograft
      rejection].

PMID- 19094714
TI  - [Biologic characteristics of pericytes and its role in angiogenesis].

PMID- 19094715
TI  - [Pathologic diagnosis of renal neoplasm].

PMID- 19094716
TI  - [Pathologic diagnosis of benign soft tissue tumors of urinary bladder].

PMID- 19094717
TI  - [Improved in specimen preparation of renal biopsies for transmission electron
      microscopy].

PMID- 19094718
TI  - [HOPE solution: a new fixation method for lung tissue].

PMID- 19094719
TI  - [Multiple primary carcinomas of thyroid and kidney coexisting with renalsolitary
      fibrous tumor: report of a case].

PMID- 19094720
TI  - [Further specialization and development of individual's professional skills is
      the way to speedily raise the standard of sciences of pathologic diagnosis in
      China.].

PMID- 19094721
TI  - [The current status and prospects of surgical management for cirrhotic portal
      hypertension].

PMID- 19094722
TI  - [The relationship of hemodynamic changes in portal hypertension and the choice of
      surgical approaches in portosystemic shunt].

PMID- 19094723
TI  - [Several issues of surgical treatments of disease of biliary tract complicating
      cirrhosis and portal hypertension].

PMID- 19094724
TI  - [Hemodynamic changes and its significance after liver transplantation for
      cirrhosis and portal hypertension].

PMID- 19094725
TI  - [The diagnosis and management of pancreatic portal hypertension].

PMID- 19094726
TI  - [Endoscope therapy of bleeding in portal hypertension].

PMID- 19094727
TI  - [A clinical study on splanchnic hemodynamic changes after orthotopic liver
      transplantation for patients with portal hypertension].
AB  - OBJECTIVE: To study the regularity of splanchnic hemodynamic changes after
      orthotopic liver transplantation (OLT) for patients with portal hypertension. At
      the same time, effect of such changes on splenomegaly, hypersplenism, collateral
      circulation and the postoperative liver function was discussed. METHODS: Between
      June 2002 and October 2005, 173 liver transplantations were performed. In 38
      patients with portal hypertension undergoing OLT, the following parameters were
      measured before surgery and subsequently at 1, 3, 5, 7 days, 1, 6 months and 1,
      2, 3 years after operation by using Color Doppler sonography: portal blood flow
      mean velocity (PBV), portal blood flow volume (PBF), hepatic artery resistance
      indexes (HA-RI) and spleen size. The same parameters were measured in 8 patients
      with acute liver failure and 20 healthy controls. Meanwhile to observe liver
      function and varicose vein of esophagus. RESULTS: In cirrhotics, PBV and PBF
      increased immediately after transplantation [from (13.7 +/- 4.2) cm/s to (58.4 +/
      25.2) cm/s and from (958 +/- 445) ml/min to (3024 +/- 1207) ml/min respectively,
      P < 0.05]. HA-RI also augmented [from (0.65 +/- 0.11) to (0.74 +/- 0.12), P <
      0.05]. PBV returned to normal values after 6 months, PBF returned to normal value
      after 2 years. Spleen size decreased significantly, but splenomegaly persisted
      after 3 years. In addition the esophagogastric varix ameliorated significantly.
      CONCLUSIONS: Abnormal splanchnic hemodynamic changes for patients with portal
      hypertension still will long-term exist after OLT, but does not effect recovery
      of hypersplenism, esophagogastric varix and liver function.

PMID- 19094730
TI  - [Experience of ultralow anterior excision for rectal cancer: 508 cases analysis].
AB  - OBJECTIVE: To investigate the operative techniques and postoperative effects of
      ultralow anterior excision for rectal cancer. METHODS: From October 1996 to
      October 2006, 508 cases with rectal carcinoma at or below the peritoneal
      reflection with potential to preserve the anal function were divided into two
      groups. Of the patients, 365 cases underwent ultralow anterior excision and
      instrumental anastomosis, and 143 cases underwent manual colon-anal anastomosis
      (Parks operation). RESULTS: In the group with anterior excision, the operations
      were all completed in the abdominal cavity, and avulsion of distal occlusive end
      occurred in 3 cases (0.9%), unsuccessful anastomosis happened in 2 cases (0.6%),
      unsatisfactory anastomosis with incomplete anastomosis circle turned out in 18
      cases (5.6%). In the Parks operation group, the anastomosis was carried out
      manually at the anus and in abdominal cavity. Postoperative defecation function
      (times, soiling underwear, feeling of urgent defecation) in the group anterior
      excision was clearly better than that in the group of Parks operation (P < 0.05);
      difficulty of defecation (sense of residual stool, prolonging of defecation,
      cathartic usage) was also better in the group with anterior excision (P < 0.05).
      The anastomosis leakage rate was 3.5% in anterior excision group, compared to
      5.6% in Parks operation group (P > 0.05). Anastomotic stenosis occurred in 77
      cases (22.5%) in anterior excision group, and 40 cases (27.9%) in Parks operation
      group (P > 0.05). The local recurrence rate and 5-year survival rate were 11.8%
      and 68.8% in anterior excision group, and 10.1% and 66.8% in Parks operation
      group, respectively (P > 0.05). CONCLUSIONS: Although there is no significant
      differences in local recurrence and 5-year survival rate between the two groups,
      the function and difficulty of defecation with instrumental anastomosis
      demonstrates clear advantages over Parks operation.

PMID- 19094728
TI  - [Function of portal pressure during operation on the choice of surgical
      approaches in portal hypertension].
AB  - OBJECTIVE: To investigate the relationship between perioperative free portal
      pressure (FPP) after devascularization or spleno-renal shunt operation added
      devascularization and rebleeding or encephalopathy in patients with portal
      hypertension, and evaluate the relationship between dynamic changes of FPP and
      surgical approaches. METHODS: The clinical data of 170 patients with portal
      hypertension receiving devascularization or devascularization with spleno-renal
      shunt operation (combination group) from January 2001 to December 2007 were
      retrospectively analyzed. All patients were divided into three groups: low
      pressure group [L group, after devascularization FPP <or= 22 mm Hg (1 mm Hg =
      0.133 kPa), n = 43], high pressure group (H group, FPP > 22 mm Hg, n = 60) and
      combination group (C group, n = 47). There was no significant difference in
      preoperative Child-Pugh score and pre-operation FPP (P > 0.05) among the three
      groups. Perioperative FPP, morbidity of rebleeding and encephalopathy were
      compared with each other. RESULTS: The values of postoperative FPP were (27.1 +/-
      1.9) mm Hg, (20.8 +/- 1.8) mm Hg and (21.5 +/- 2.2) mm Hg among the H group, L
      group and C group respectively. The rebleeding rates were 21.7%, 4.6% and 4.5%
      among the three groups respectively. All the values in H group were higher than
      those in L group and C group remarkably. The encephalopathy rate in C group
      (10.4%) was higher than that in L group (7.0%) or H group (3.3%), but there were
      no statistical significance (P > 0.05). CONCLUSIONS: FPP after splenectomy and
      devascularization may be a basis of choice of surgical approaches in portal
      hypertension. The spleno-renal shunt operation should be performed in the
      patients when FPP is over 22 mm Hg after devascularization.

PMID- 19094731
TI  - [Surgical treatment of 154 patients with non-traumatic acute lower limb
      ischemia].
AB  - OBJECTIVE: To analyze the surgical treatment and prognosis of non-traumatic acute
      lower limb ischemia, and compare the morbidity and prognosis of acute arterial
      embolism and acute arterial thrombosis. METHODS: The clinical data of 154 acute
      lower limb ischemia patients surgically treated from July 1999 to December 2007
      were retrospectively analyzed. Fogarty catheter embolectomy was used in all
      patients; in which, 128 cases underwent Fogarty catheter embolectomy only, 8
      cases Fogarty catheter embolectomy combined with endarterectomy, 13 cases Fogarty
      catheter embolectomy combined with vascular reconstruction with prosthetic graft
      or great saphenous vein, 5 cases Fogarty catheter embolectomy combined with
      amputation. The patients were divided into two groups according to pathogenesis:
      acute arterial embolism group (99 cases) and acute arterial thrombosis group (55
      cases). The morbidity, amputation, perioperative mortality rates and high risk
      factors of amputation in the two groups were compared. RESULTS: Female
      experienced acute arterial embolism more often than man (60.6% vs 39.4%, P <
      0.05), and more acute arterial thrombosis occurred in man (72.7% vs 27.3%, P <
      0.05). The amputation rate of all cases was 9.7%, and perioperative mortality
      rate was 11.7%. The amputation rate in acute arterial embolism group was lower
      than acute arterial thrombosis group (5.1% vs 18.2%, P < 0.05). The perioperative
      mortality rates in the two groups were equal (11.1% vs 12.7%, P > 0.05). The
      statistically high risk factor of amputation for two groups was ischemic time,
      and smoking and diabetes were high risk factors for acute arterial thrombosis.
      CONCLUSIONS: Men experiences acute arterial thrombosis more often, and women
      experiences acute arterial embolism more often. The amputation rate of acute
      arterial embolism is lower than acute arterial thrombosis, and acute arterial
      thrombosis has more high risk factors of amputation.

PMID- 19094733
TI  - [Video-assisted thoracoscopic extended thymectomy for myasthenia gravis].
AB  - OBJECTIVE: To investigate the outcome of video-assisted thoracoscopic extended
      thymectomy (VATET) for myasthenia gravis. METHODS: From January 2005 to February
      2006, VATET had been performed for 41 patients of myasthenia gravis. Among them,
      23 patients were female and 18 were male. The age ranged from 18 to 67 years old,
      and the disease duration ranged from 1 month to 3 years. In order to achieve
      maximal benefit, a transverse cervical incision was given access to the peri
      thyroid space to remove fat in the neck which may contain ectopic thymus after
      all thymic tissue, including far-reaching ectopic sites. Peri-thymic adipose
      tissue in the anterior mediastinum was completely removed. RESULTS: In the 41
      patients, mean operative time was 162 min. Sever patients sustained myasthenic
      crises that required reintubation and mechanical ventilation for a few days. Of
      all patients, 35 had lymphadenectasis, and 4 had ectopic thymus in the peri
      thyroid space. After the 2 years' follow-up, the rate of complete stable
      remission was 41.4%, and the effective rate was 85.4%. CONCLUSIONS: Video
      assisted thoracoscopic thymectomy represents a safe and valid approach for
      patients with myasthenia gravis. VATET may be a complement to completely remove
      all thymus including ectopic tissues.

PMID- 19094734
TI  - [Research on application of modified polyethylene glycol hydrogels in the
      construction of tissue engineered heart valve].
AB  - OBJECTIVE: To explore the effect of the polyethylene glycol (PEG)-hydrogels to
      enhance the seeding-cells adhesion to the biomaterial scaffolds. METHODS: Sixteen
      porcine aortic valves were decellularized with Triton X-100 and trypsin, then
      divided into A and B group, eight in each group. Group A: the donor goat's
      autologous bone marrow mesenchymal stem cells (BMSCs) Selected as the seeding
      cells were encapsulated into the modified PEG-hydrogels to complete the process
      of the cells attaching to the acellular porcine aortic valves. Non-PEG but
      reservation of BMSCs was modified in Group B. After static culture for 7 d, the
      mono semilunar tissue engineering heart valve (TEHV) were implanted respectively
      into each donor goat's abdominal aortas. Gross and histology examination,
      ultrasonic scanning, electron microscopy observation and biomechanics detection
      were performed at 16 weeks after operation. The 8 native goat aortic valves from
      the donor goats were selected at the same time as control group (Group C).
      RESULTS: There were much more improvements compared Group A to Group B (P < 0.05)
      in tensile strength [(12.9 +/- 1.3) MPa vs. (8.8 +/- 0.4) MPa], ratio of re
      endothelial (84.6% vs. 14.8%) and mural thrombosis (0/8 vs. 8/8). The data
      illustrated the critical importance of BMSCs differentiation to endothelial and
      myofibroblast for remodeling into native tissue in microenvironment in vivo.
      CONCLUSIONS: It is feasible to reconstruct TEHV efficiently by combining modified
      PEG-hydrogels with acellular biomaterial scaffold and autologous MSCs cells. It
      can improve the integration of the seeding-cells and scaffold. It can also
      protect the growth and differentiation of the BMSCs in the systemic circulation
      effectively.

PMID- 19094735
TI  - [Repair of anterior leaflet mitral valve prolapse: the comparison between chordal
      replacement and chordal shortening].
AB  - OBJECTIVE: To compare the relative merits between chordal shortening and
      artificial chordae to repair the anterior leaflet prolapses (ALP). METHODS: The
      clinic data of 50 cases underwent repair of ALP from March 1990 to March 2008
      were analyzed retrospectively. There were 29 male and 21 female patients with a
      mean age of (42.6 +/- 11.3) years old. There were 23 patients in chordal
      shortening group and 27 patients in artificial chordae group. RESULTS: There were
      3 operative deaths in chordal shortening group (13.0%), and 1 death in artificial
      chordae group (3.7%, P = 0.199). With a mean follow-up of (5.8 +/- 4.8) years and
      a total follow-up of 278 patient-years, there were 3 late deaths respectively in
      each group. According the Kaplan-Meier survival curve, the actuarial survival
      rate at 5-8 years was 70.0% +/- 18.2% for chordal shortening group and 86.8% +/-
      9.2% for artificial chordae group (chi(2) = 8.17, P = 0.046). There were 5
      reoperations, of which 4 in chordal shortening group and 1 in artificial chordae
      group. According to the Kaplan-Meier freedom from reoperation curve, the freedom
      from reoperation at 5 years was 83.3% +/- 15.2% for chordal shortening group and
      100% for artificial chordae group (chi(2) = 12.06, P = 0.007). The COX
      proportional hazard regressions revealed that chordal-shortening technique was
      the independent risk predictor for the late cardiac event after ALP surgical
      repair. CONCLUSION: Artificial chordae techniques has a relative superiority to
      chordal shortening for repair of mitral valve ALP.

PMID- 19094736
TI  - [The surgical treatment and outcome of nonmetastatic osteosarcoma of the
      extremity with pathologic fractures].
AB  - OBJECTIVE: To demonstrate the influence of pathologic fracture and the form of
      surgical therapy on the survival rate and the prognosis of the patients with
      osteosarcoma. METHODS: From 1992 to 2001 retrospective analysis was done for 22
      patients with pathological fracture out of 189 patients with primary extremity
      osteosarcoma. The 22 patients presented as primary extremity osteosarcoma with
      pathologic fracture without prior treatment. They were 7 females and 15 males and
      their age ranged from 8 to 36 years old. Most of diseases located in humerus and
      femurs. Limb salvage underwent in 12 patients (allograft 2, bone cement spacer 4,
      local resection 1, prosthesis 4 and rotation-plasty 1) and amputation in 10. All
      these patients had pre and post operative chemotherapy. The 22 patients followed
      8 to 146 months after surgery, and the average was 54.7 months. The minimum
      follow-up for survive patient was 36 months. RESULTS: The 54.5% patients had limb
      salvage surgery and 45.5% had amputation, and the limb salvage was lower than non
      fracture patients (71.9%), but without significance (P = 0.096). Nine patients
      developed lung metastases and died in 8 to 26 months postoperatively. The five
      year estimated survival rate was 53.4%. The recurrent rates were 16.7% and 10.0%
      in limb salvages and amputation respectively. The lung metastases rates were 25%
      and 60% in limb salvages and amputation respectively. CONCLUSION: The performance
      of a limb-salvage procedure in carefully selected patients with pathologic
      fracture does not significantly increase the risk of local recurrence or death.

PMID- 19094737
TI  - [Total elbow arthroplasty after resection of tumors at the elbow].
AB  - OBJECTIVE: To explore the effects and complications of the total elbow
      arthroplasty after the resection of the peri-elbow tumor. METHODS: Between June
      1998 to June 2007, 19 patients underwent total elbow arthroplasty after resection
      of tumors at the authors department, which involved 13 males and 6 females,
      including 6 patients with metastatic tumor, 1 with giant cell tumor of bone
      (GCT), 2 with malignant fibrous histiocytoma (MFH), 4 with osteosarcoma, 3 with
      Ewing sarcoma, l with lymphoma, 1 with synovial sarcoma, and 1 with desmoid
      fibroma of the bone. The age of patients ranged from 15 to 71 years (mean 43
      years). LOCATION: distal humerus in 9 cases, proximal ulna in 5 and the tumor
      involving both distal humerus and proximal ulna in 5 patients. RESULTS: Patients
      were evaluated according to the Mayo Elbow Performance Score. Pain scores
      decreased from a mean of 3.6 to 2.0. Mean arc of elbow motion from extention to
      flexion improved from 30 to 80 (range, 55 - 105). Fourteen elbows had excellent
      or good result (14/19, 77.8%), and 4 elbows had a poor result (22.2%). There was
      no wound infection or other complication after surgery. During the following up
      time, 2 patients with metastatic lung cancer, 1 with metastatic rectal cancer and
      1 with ovarian cancer died in 2 years after surgery. Two Ewing sarcoma, 1 MFH and
      1 osteosarcoma patients occurred lung metastasis (4/18, 22.2%), and two patients
      had local recurrence (11.1%). Three patients occurred complication during the
      following time (3/18, 16.7%), the stem of humerus prosthesis came out of channel
      in 1 case 5 years after surgery, the stem of ulna prosthesis came out of channel
      in 1 case 4 years after surgery, and both cases did revision surgery. The stem
      loosening was in 1 humerus prosthesis 4 years after surgery. CONCLUSIONS: The
      results show that total elbow arthroplasty after resection of tumors can decrease
      the pain, and improve the function substantially. For metastatic tumors, this
      technique also can be used if there is no other good option.

PMID- 19094739
TI  - [Digital skeletal age and histological evaluation for residual spine growth
      potential in idiopathic scoliosis].
AB  - OBJECTIVE: To ascertain the correlation between histological grades (HGs) of
      vertebral growth plates and Risser grades in idiopathic scoliosis (IS) patients;
      to identify whether digital skeletal age (DSA) is a reliable indicator for
      accurate evaluation of the spinal residual growth potential. METHODS: Twenty
      eight Chinese female patients were available for this study. Superior and
      inferior growth plates were obtained at each level when anterior approach
      surgeries were performed. Histological examinations were conducted after the
      specimens were processed. The patients were evaluated by DSA stages in this
      study. Correlations between histological grades, menarchal status, and
      chronological age were analyzed. RESULTS: There was a negative correlation
      between the following: HGs and DSA stages in 28 cases (r = -0.541, P = 0.003),
      and HGs and menarchal status in patients in DSA stage III (r = -0.591, P =
      0.006). Statistical significance of growth activity of growth plates was found
      between patients in DSA-stage II and those in DSA-stage III (P = 0.014).
      CONCLUSIONS: DSA may be a reliable indicator for predicting the spinal residual
      growth potential in IS patients, but it should be correlated with menarchal
      status and chronological ages.

PMID- 19094740
TI  - [Genetic polymorphism of growth hormone gene in adolescent idiopathic scoliosis].
AB  - OBJECTIVE: To investigate whether the growth hormone gene (GH) promotor
      polymorphism (rs2854184) is associated with the occurrence or curve severity of
      adolescent idiopathic scoliosis (AIS). METHODS: Two hundred and sixty-five AIS
      patients and 193 normal controls were recruited. The maximum Cobb angles were
      recorded in AIS patients. PCR-RFLP was used for the genotyping. RESULTS: The
      genotype frequency distribution were AA 38.3%, AT 50.3%, TT 11.4% in AIS patients
      and AA 39.6%, AT 50.2%, 10.1% TT in controls for the promotor polymorphism
      rs2854184 in GH gene. It was comparable between AIS and normal control. The
      allele frequency distribution was also comparable between AIS and normal control.
      It was 63.5% for allele A, 36.5% for allele T in AIS patients and 64.7% for
      allele A, 35.3% for allele T in normal control. The mean maximum Cobb angle in
      AIS patients with AA, AT, TT genotypes were 33.8 degrees +/- 10.0 degrees, 36.4
      degrees +/- 15.0 degrees, 34.5 degrees +/- 9.1 degrees, respectively, it was
      similar with each other. CONCLUSION: The GH gene promoter polymorphism is neither
      associated with the occurrence nor the curve severity of AIS.

PMID- 19094748
TI  - [Key issues and prospects for the study on metastasis of hepatocellular
      carcinoma].

PMID- 19094741
TI  - [Study on small diameter artificial vascular graft with eNOS gene transfected
      endothelial cells in canine].
AB  - OBJECTIVE: To investigate the patency efficacy of small diameter artificial
      vascular graft with eNOS gene transfected endothelial cells in canine. METHODS:
      By using the two steps high pressure injection, eNOS gene transfected endothelial
      cells were planted on artificial vascular graft with a diameter of 3 mm. The
      artificial vascular grafts were transplanted into canine femoral artery, and the
      patency of the artery was observed through digital subtracted angiography (DSA)
      and electron telescope 1, 4, 12 and 24 weeks after the operation. RESULTS: The
      adherence rate of eNOS gene transfected endothelial cells to artificial vascular
      grafts was up to 90%. For 10 days, the cells extended and formed a continuous
      intima. One week after the operation, 3/9 grafts were obstructed in the group of
      simple artificial vascular grafts; 4 weeks after, all of grafts (9/9) were
      obstructed in the group of simple artificial vascular grafts and almost half
      grafts (5/10, 4/9) in un-transfected groups were obstructed; 12 weeks after, all
      of the grafts were obstructed in the group of simple artificial vascular grafts
      and in un-transfected groups (9/9, 9/10); 24 weeks after, all of the grafts were
      obstructed in the groups of un-transfected artificial vascular grafts, while
      nearly all of grafts (8/10) were open in eNOS groups. Electron microscope
      scanning showed that endothelial cells of artificial vascular grafts in eNOS
      transfected groups arranged closely and formed a continuous intima; only few red
      blood cells, leucocytes, platelets deposited at the surface of endothelial cells
      in the artificial vascular grafts. CONCLUSIONS: The patency efficacy of eNOS gene
      transfected endothelial cells planting on artificial vascular graft is
      satisfactory. It could provide an experimental basis for further clinical
      application of the artificial vascular grafts.

PMID- 19094749
TI  - [Strategy to improve the prognosis of liver transplantation for hepatocellular
      carcinoma].

PMID- 19094750
TI  - [Basic and clinical study of interferon a in hepatocellular carcinoma].

PMID- 19094751
TI  - [Recurrence and metastasis of hepatocellular carcinoma after liver
      transplantation: single center experiences].
AB  - OBJECTIVE: To study the clinical features and treatment of recurrent
      hepatocellular carcinoma after liver transplantation. METHODS: Clinical data of
      95 patients with recurrent hepatocellular carcinoma (HCC) after liver
      transplantation from January 2003 to November 2005 were analyzed retrospectively.
      RESULTS: During follow-up, 42 patients (43.2%) were diagnosed HCC recurrence. The
      predominant sites of recurrence were liver graft (32 cases), lung (21 cases),
      bone (7 cases). Tumor size, tumor distribution, liver cirrhosis, pre-transplant
      AFP level, tumor differentiation, macrovascular invasion were considered risk
      factors of both post-transplant survival and HCC recurrence in univariate
      analysis. Tumor distribution, tumor differentiation, macrovascular invasion were
      considered independent risk factors of both overall post-transplant survival and
      HCC recurrence in multivariate analysis. Intervention therapy and internal
      radiation of recurrent HCC could delay tumor progression and resection of
      recurrent HCC in selected patients can significantly prolong post-recurrence
      survival. CONCLUSIONS: Carefully selection of HCC patients as candidates for
      liver transplantation can significantly reduce HCC recurrence. At the present
      stage, surgical resection of recurrent HCC is the best treatment method in
      selected patients.

PMID- 19094752
TI  - [Treatment of postoperative recurrence of hepatocellular carcinoma with
      radiofrequency ablation comparing with repeated surgical resection].
AB  - OBJECTIVE: To evaluate the efficacy of radiofrequency ablation for the treatment
      of postoperative recurrence of hepatocellular carcinoma and whether
      radiofrequency ablation can be used as first line treatment for recurrent
      hepatocellular carcinoma. METHODS: There were 213 patients with small recurrent
      hepatocellular carcinoma (tumor size of 3 cm or less and no more than 3 nodules)
      who treated in Liver Cancer Institute, Fudan University from January 2000 to
      December 2005. Among these patients 68 were treated with radiofrequency ablation
      and 145 were treated with repeated surgical resection. Kaplan-Meier method was
      used to evaluate the overall survival or disease free survival. Log-rank used to
      determine the survival difference between groups and COX proportional hazard was
      used for multivariate analysis to evaluate the risk factors for prognosis. The
      overall survival or disease free survival was calculated from the time treated
      with radiofrequency or repeated surgical resection. RESULTS: The 1-, 3-, 5-years
      overall survival rates were 94.7%, 65.1%, 37.3% and 88.1%, 62.6%, 41.0% in
      radiofrequency ablation group and surgical repeated resection group,
      respectively. There was no significant difference between two groups (P = 0.693).
      However, the disease free survival was better in repeated surgical resection than
      in radiofrequency ablation, which were 79.4%, 48.1%, 34.4% and 58.0%, 27.8%,
      12.4% in repeated surgical resection and radiofrequency ablation, respectively (P
      = 0.001). The interval between recurrence and initial hepatectomy with more than
      2 years was independent factor favor to good prognosis. CONCLUSIONS:
      Radiofrequency ablation seems to be as effective as repeated surgical resection
      owing to comparable overall survival and can be considered as alternative therapy
      for surgical resection treatment of small recurrent hepatocellular carcinoma.

PMID- 19094753
TI  - [Percutaneous radiofrequency ablation combined with other minimally invasive
      treatments for recurrent hepatocellular carcinoma after hepatectomy].
AB  - OBJECTIVE: To evaluate the efficacy and safety of percutaneous radiofrequency
      ablation (PRFA) and combined with other minimally invasive treatments for
      recurrent hepatocellular carcinoma (RHCC) after hepatectomy. METHODS: Eighty-four
      patients with RHCC after hepatectomy who were treated with PRFA or combined with
      other minimally invasive therapies between August 1999 and February 2008 were
      analyzed retrospectively. RESULTS: There was no treatment related mortality in
      the study population, and the morbidity was 2.4% (2/84). The complete ablation
      rate was 94.0% (79/84), and the 1-, 3- and 5-year overall survival rates were
      74.9%, 54.9% and 48.2%, respectively. The 1-, 3- and 5-year overall survival
      rates of patients with recurrent interval after hepatectomy less than 1 year and
      over 1 year were 72.1%, 36.2%, 24.2% and 76.8%, 70.6% and 65.1%, respectively (P
      = 0.040). The 1-, 3- and 5-year overall survival rates of patients with tumor
      size <or= 3 cm and > 3 cm were 83.2%, 67.7%, 67.7% and 59.1%, 24.2%, 12.1%,
      respectively (P = 0.003). The 1-, 3- and 5-year overall survival rates of
      patients treated with PRFA alone and combined with percutaneous ethanol injection
      (PEI) were 66.7%, 33.3%, 22.2% and 76.5%, 57.3%, 57.3%, respectively (P = 0.017).
      The 1-, 3- and 5-year overall survival rates of patients treated with PRFA alone
      and combined with transcatheter hepatic arterial chemoembolization (TACE) were
      55.6%, 24.7%, 24.7% and 81.6%, 66.0%, 57.5%, respectively (P = 0.001).
      CONCLUSIONS: PRFA is an effective and safe treatment for RHCC, and tumor size and
      recurrent interval after hepatectomy are important prognostic factors.
      Combination with PEI or TACE may improve the efficacy of PRFA for treatment of
      RHCC.

PMID- 19094754
TI  - [Primary experience of the anatomical laparoscopic left lateral hepatic lobectomy
      procedure for benign and malignant liver tumors].
AB  - OBJECTIVE: To assess the feasibility, safety and outcome of anatomical
      laparoscopic left lateral hepatic lobectomy for benign and malignant liver
      tumors. METHODS: From April 2005 to May 2008, 11 patients (7 male, 4 female; mean
      age 51.7 years) underwent anatomical laparoscopic left lateral hepatic lobectomy.
      Four patients presented with hepatocellular carcinoma and cirrhosis, while 1
      patient had metastatic liver tumors from postoperatively colon cancer, five
      patients had hemangioma (2 cases with gallstones underwent cholecystectomy), 1
      patient had a huge symptomatic angiolipoleiomyoma. Mean tumor size was 5.8 cm
      (range 2.1 to 12.0 cm). All the lesions were localized in the anatomical left
      lateral lobe (segments II to III). RESULTS: The mean operative time was 147 min
      (range 120 to 180 min). There were no intraoperative or postoperative
      complications, and blood transfusions were not required. The mean postoperative
      hospital stay was 5.9 days. CONCLUSIONS: Anatomical laparoscopic left lateral
      hepatic lobectomy are feasible and safety.

PMID- 19094755
TI  - [Relationship between epithelial-mesenchymal transition and lung metastasis in
      hepatocellular carcinoma].
AB  - OBJECTIVE: To evaluate the relationship between epithelial mesenchymal transition
      (EMT) and lung metastasis in hepatocellular carcinoma. METHODS: There were 100
      patients who underwent surgical resection of hepatocellular carcinoma between
      January 2000 and March 2004. They were classified with non-distance metastasis
      and lung metastasis depend on the close following up till March 2007. Their
      hepatocellular carcinoma specimens were retrospectively examined for EMT markers
      (E-cadherin, Vimentin, Fibronectin) with immunochemistry staining in tissue
      microarray. Univariate and multivariate analysis were used for study the
      relationship between EMT and lung metastasis. RESULTS: Univariate analysis showed
      that down regulation of E-cadherin, overexpression of fibronectin, cytosolic
      expression of vimentin, AFP >or= 400 ng/ml, tumor size more than 10 cm, portal
      vein involvement, poorly differentiated of tumor had close correlation with lung
      metastasis. Multivariate analysis indicated that overexpression of fibronectin
      was independent factor for lung metastasis apart from tumor size more than 10 cm,
      portal vein involvement and poorly differentiated of tumor. CONCLUSION: The
      results proposed that EMT has close relation with lung metastasis in
      hepatocellular carcinoma.

PMID- 19094757
TI  - [Ultrasound-guided percutaneous tube drainage combined with directly-viewed
      debridement with cholangioscopy: a mini-invasive strategy for peripancreatic
      necrotizing infection].
AB  - OBJECTIVE: To establish "an integrative therapy" of drainage and debridement on
      peripancreatic necrotizing infection (PPNI) with minimally invasive technique,
      and to detect its clinical effects. METHODS: There were 17 patients who accepted
      ultrasound-guided percutaneous tube drainage combined with directly-viewed
      debridement with cholangioscopy from March 2006 to January 2008. Percutaneous
      puncture and catheter (6 - 8 F) drainage were adopted on the patients suffering
      from PPNI with B-us guidance, then the drainage sinus was expanded progressively
      from 8 F to 24 F in diameter with Cook fascia dilator by degrees, and the 22 F or
      24 F tube was easily placed into the interior of PPNI instead of the prior
      catheter. So a better drainage effect was achieved. One week later, the
      necrotizing tissue of PPNI could be observed and debrided with choledochoscope
      under a directly-viewed way through the enlarged new sinus. Thus, with the
      continuous tube drainage and repeated debridement, the focus was absorbed and
      covered gradually. RESULTS: Seventeen cases accepted the mini-invasive therapy,
      15 cases were saved finally with cure rate of 88.2%, and 2 cases conversion to
      laparotomy because of some technical reasons. The mean healing time was 73 days,
      and the mean hospitalization time was 57 days. Bleeding was occurred in 2 cases
      localized in sinus and the inside of PPNI, digestive tract fistula was detected
      in 2 cases, and these patients with the complications were cured under
      nonoperative management. All the patients were still alive with following-up,
      neither remains nor recurrence of the PPNI was found in our group. CONCLUSIONS:
      Ultrasound-guided percutaneous tube drainage combined with directly-viewed
      debridement with cholangioscopy, as a mini-invasive therapy, could complete the
      goal-directed therapy of PPNI, meanwhile, realize the modern surgery ideal of
      damage control.

PMID- 19094758
TI  - [Clinicopathologic characteristics and postoperative prognosis in colorectal
      cancer with peritoneal dissemination].
AB  - OBJECTIVE: To investigate the correlation between clinicopathologic factors and
      peritoneal dissemination in colorectal cancer, and the impact of surgery on the
      prognosis of patients with peritoneal dissemination. METHODS: Based on the
      clinical database built in 1994, the clinicopathologic data and the result of
      follow-up of all colorectal cancer patients were analyzed retrospectively.
      RESULT: One hundred and fifty cases (7.40%) in all 2019 patients with primary
      colorectal cancer were found complicated with peritoneal dissemination. The
      clinicopathologic factors in patients with peritoneal dissemination were
      significantly correlated with tumor penetrating through serosa, lymph node
      metastasis, undifferentiated carcinoma, ascites, different pathological type,
      circumference of tumor, neoplastic intestinal obstruction, and Dukes staging.
      Peritoneal dissemination was associated with tumor penetrating through serosa,
      different pathological type on multivariate analysis. The 1-, 3-, 5-year survival
      rate of the patients with peritoneal dissemination were 70.4%, 38.1%, 30.2%; The
      1-, 3-, 5-year survival rate of the patients undergoing radical resection were
      significant better than those in the cases undergoing palliative operation or
      palliative resection (P < 0.05). CONCLUSIONS: Colorectal cancer complicated with
      peritoneal dissemination has poorer clinicopathologic characteristics. Those with
      local peritoneal dissemination has rather better prognosis than those with wide
      peritoneal dissemination. Radical resection of the disseminated tumor can improve
      the prognosis of the patients.

PMID- 19094759
TI  - [Short to midterm results of endovascular for 105 case of infrarenal abdominal
      aortic aneurysms].
AB  - OBJECTIVE: To assess short to midterm outcome of endovascular aneurysm repair
      (EVAR) of infrarenal abdominal aortic aneurysms (AAA) in 105 cases. METHODS:
      Stent-grafts were placed into 105 patients with infrarenal AAA between January
      2001 and February 2007. The clinical data of those cases were retrospectively
      analyzed. RESULTS: Primary technical success rate was 100%. Eighty-two cases
      (78.09%) were followed-up for 1 to 73 months (mean, 8.9 +/- 5.8 months). Three
      cases (2.86%) died during peri-operative period, from acute cardiac infarction,
      multi-organ failure and significant upper gastrointestinal bleeding,
      respectively. Another one died from hepatic cancer 30 months after EVAR. Twenty
      one cases experienced primary endoleak. Eighteen were type I, among which 10
      underwent secondary intervention in the form of balloon dilatation (n = 9) and
      stent-graft placement (n = 1), 8 sealed spontaneously. Two cases were type II and
      sealed spontaneously. One type III was treated by placing a stent-graft. An
      emergent femorofemoral crossover was performed for one graft limb thrombosis 2
      weeks after EVAR. Four late type I endoleaks occurred. One stent-graft migration
      without endoleak was cured conservatively. Two stent-graft infections occurred 1
      month and 3 months after EVAR respectively, and were cured with debridement,
      drainage and antibiotics. Nine femorofemoral or iliofemoral bypass and three
      internal iliac bypasses were all patent during the follow-up period. CONCLUSION:
      Endovascular repair is a safe and effective method for infrarenal AAA with
      perfect short to midterm outcomes.

PMID- 19094760
TI  - [Sagittal diameters measurements on MR of the cervical spinal cord in normal
      subjects].
AB  - OBJECTIVE: To offer normal reference of diameter of the cervical spinal cord and
      available diameter of cervical spinal canal and to screen scientific radiographic
      criteria to define and quantify cervical spinal cord disease. METHODS: The
      magnetic resonance images of 120 normal people had been measured. The data of
      diameters of cervical spinal cord, CSF, M, the ratio of diameters of cord and
      CSF, and the ratio of diameters of cord and M had been collected and statistical
      analysis was made. And the relationships between the data above and each of
      gender, the length of C-spine and age were evaluated. In addition, the ratio of
      diameters of cord and CSF, and the ratio of diameters of cord and M was
      evaluated. RESULTS: The study showed that in healthy people, the diameters of
      cervical spinal cord, CSF and M was larger in the males than in the females,
      decreased with age, and increased with the length of C-spine but the diameter of
      CSF. And the ratio of diameters of cord and CSF increased with age and not
      affected by the length of C-spine. However, the ratio of diameters of cord and M
      was not affected by age and the length of C-spine. CONCLUSION: The ratio of
      diameters of cord and M is not affected by individual variation and can be used
      to evaluate cervical spinal cord atrophy, compression and impaired in patients
      with cervical myelopathy and can be important information in looking for
      clinically critical points.

PMID- 19094761
TI  - [Malignant giant cell tumor of the tendon sheaths in the hand].
AB  - OBJECTIVES: To retrospectively study on malignant giant cell tumor of tendon
      sheath (MGCTTS) in the hand, and to evaluate its clinical, histologic,
      immunohistochemical features and biologic evolution. METHODS: Between January
      1991 and December 2001, 10 patients with histologically proven MGCTTS were
      treated. The clinical material, radiographs and hematoxylin and eosin-stained
      sections were reviewed. Immunohistochemical studies and nuclear suspensions for
      flow cytometry were done on paraffin embedded tissue. All patients were followed
      up. RESULTS: Three of 10 patients in which the diagnosis of MGCTTS was originally
      considered were excluded after the slides reviewed and immunohistochemical
      examination performed. In the other 7 patients, one showed malignant and
      aggressive nature: the lesion recurred several times and the patient eventually
      died with pulmonary metastases. The immunohistochemical profile of the patient
      was similar to that reported in benign GCTTS, and the flow cytometry DNA analysis
      detected aneuploidy. Six cases presented histologic features of malignancy, 4 of
      them undertook the immunohistochemical examination and their profiles were
      similar to that reported in benign GCTTS. An aneuploidy DNA pattern was detected
      in one case on flow cytometry evaluation, diploidy DNA pattern was detected in 3
      cases, and their S-phase fraction was 4.5%, 11.6% and 2.6% respectively. All of
      them had a benign clinical features, they were alive and without evidence of
      disease from 1.5 to 7.5 years (averagely, 4.5 years) after complete surgical
      excision or resections with wide surgical margins. None of them had received
      chemotherapy or radiation therapy. CONCLUSIONS: Malignant giant cell tumor of
      tendon sheath is an extremely rare malignant tumor, some cases have a poor
      outcome, the others, despite the histologically malignant features, have a good
      prognosis if wide surgical excision ablates the tumor completely.

PMID- 19094762
TI  - [Analysis in primary clinic outcomes of minimal extracorporeal circulation in the
      coronary artery bypass grafting].
AB  - OBJECTIVE: To analysis comparatively the primary clinic outcomes between minimal
      extracorporeal circulation (MECC) and conventional extracorporeal circulation
      (cECC). METHODS: Forty cases accepted coronary artery bypass grafting from August
      to October at 2006 were divided into MECC group and cECC group at random, 20
      cases for each group. Record and analysis of the general information, clinic data
      perioperatively, and complications postoperatively for each group were performed.
      RESULTS: There were no deference between groups in gender, anamnesis and
      preoperative cardiac function, while age (P < 0.05), standard EuroSCORE and
      logistic EuroSCORE were much more higher in MECC group than in cECC group (P <
      0.01). Similarly, there were no deference in operative time, bypass time,
      ischemic time and graft number between two groups. Contrasted with cECC group,
      the values of cTNI were lower in MECC group at 2 h, 6 h and 12 h post-ECC (P <
      0.01), oxygen index were higher post-operatively and there was a statistic
      deference at 12 h post-ECC (P < 0.05). The valves of ALT and TBIL in cECC group
      were higher abnormally at early post-ECC, and significant higher than in MECC
      group at 2 h, 6 h post-ECC of ALT (P < 0.05), and at termination, 2 h post-ECC of
      TBIL (P < 0.05). The values of activated partial thromboplastin time were almost
      at physiological status in MECC group, but were significantly prolonged in cECC
      group at early post-ECC, and were statistically longer than in MECC group at 2 h,
      6 h, 12 h post-ECC (P < 0.05). The concentration of free hemoglobin in cECC group
      were higher than in MECC group peri-operative, and there was a statistic
      deference at 2 h post-ECC (P < 0.05). There were no deference between the two
      group in Cr, PLT and WBC. CONCLUSIONS: Compared with cECC, MECC carries more
      biocompatibility, more safe and credible. MECC system can alleviate the organ
      injury postoperatively and decrease the incidence of complications, especially in
      high-risk patients.

PMID- 19094763
TI  - [Efficacy and safety of long-acting gonadotropin-releasing hormone analogue in
      the treatment for metastatic prostate cancer].
AB  - OBJECTIVE: To evaluate the efficacy and safety of gonadotropin-releasing hormone
      analogue (GnRHa) triptorelin 11.25 mg 3-month sustained release formulations in
      the treatment of metastatic prostate cancer. METHODS: From January 2004 to March
      2006, a randomized, parallel-controlled, multicenter clinical trial was
      conducted. One hundred and twenty-seven patients with documented metastatic
      prostate cancer were randomized to receive one injection of the 11.25 mg
      formulation triptorelin (n = 65) or three injections at 28-day intervals of the
      3.75 mg formulation (n = 62). Changes from baseline of TPSA, prostate volume,
      testosterone, LH, FSH, PRL and estradiol were assessed over 3 months. Changes of
      the metastatic lesions were also observed and evaluated. The occurrences of
      adverse events were evaluated as well. RESULTS: After 3 months treatment, total
      PSA level decreased significantly from baseline both in 11.25 mg group and 3.75
      mg group. At 30, 60 and 90 days, TPSA (median level) declined from 164.55
      microg/L into 11.34, 4.12, 3.89 microg/L in 11.25 mg group, and from 101.38
      microg/L into 6.88, 2.41, 2.57 microg/L in control group respectively. The
      patients ratio with over 90% decreasing from TPSA baseline were 78.6% and 75.5%
      respectively in two groups (P = 0.700). Prostate volume were also decreased
      significantly in both groups, median volume declined from 48.0 mm(3) into 21.5
      mm(3) in 11.25 mg group and from 45.0 mm(3) into 21.0 mm(3) in 3.75 mg group. No
      significant differences were found between the two groups in changes of TPSA (P =
      0.601) and prostate volume (P > 0.05). Both formulations were able to induce
      castration levels, 0.31 microg/L in 11.25 mg group and 0.26 microg/L in 3.75 mg
      group (P > 0.05). 13.8% and 17.7% of adverse events were recorded respectively in
      two groups, and no differences were found (P = 0.547). CONCLUSION: As a new long
      acting sustained release formulation, triptorelin 11.25 mg is comparable to
      triptorelin 3.75 mg formulation in the aspect of efficacy and safety for the
      treatments of metastatic prostate cancer.

PMID- 19094764
TI  - [Clinical study and numerical simulation of hemodynamics in the tortuosity of
      internal carotid artery].
AB  - OBJECTIVES: To establish a theoretical model for the tortuosity of internal
      carotid artery and summarize the hemodynamic rule of blood flow in a tortuous
      artery. To explore the relationship of cerebral ischemia and tortuous internal
      carotid artery. METHODS: Taking the internal carotid artery as a prototype, a
      geometric model of a tortuous artery was constructed according to the normal
      physiological and anatomical parameters of internal carotid artery. The boundary
      conditions and calculation conditions of blood flow are proposed. The numerical
      simulation of the blood flow in the tortuous artery is carried out with finite
      element method. Hemodynamic parameters of internal carotid artery were measured
      in 15 cases with the tortuosity of internal carotid artery and in 15 cases of
      normal control group. Blood pressure was measured by microcatheter connecting a
      pressure transducer at internal carotid artery, pre-tortuous and post-tortuous
      artery. The diameter and length of the above artery were measured and calculated
      by DSA machine. RESULTS: Numerical simulation results indicated pressure drop of
      blood flow and elongated length of artery is increased with diminution of the
      angle of tortuous artery. Clinical measurement data disclosed the same trend in
      the same curve as numerical simulation. CONCLUSION: The elongation and tortuosity
      of internal carotid artery results in decrease of blood pressure in the distal
      segment of tortuous internal carotid artery, kinking of internal carotid artery
      may be one of factors related to attack of cerebral ischemia on certain
      conditions.

PMID- 19094765
TI  - [Fabrication and characteristics of oriental poly (lactic-co-glycolic acid)
      scaffold: a preliminary study].
AB  - OBJECTIVE: To explore the method of fabricating oriental scaffolds and
      investigate the biocompatibility of the scaffolds as well as cells distribution
      within the scaffolds in vitro. METHODS: The oriental poly (lactic-co-glycolic
      acid) (PLGA) scaffolds were fabricated with modified emulsion-phase separation
      method. The scaffolds were treated with plasma and then anchored with collagen I.
      Articular chondrocytes were loaded into the scaffolds. The growth status and
      distributing characteristic of the cells were investigated by environmental
      scanning electron microscope. RESULTS: The scaffold was well compatible with the
      articular chondrocytes. The cells could reach to 2.5 mm depth with unilateral
      loading. The cells distributed evenly in the scaffold and lined along the inner
      pipes. CONCLUSIONS: The oriental scaffold fabricated could significantly promote
      the distributing characteristics of the chondrocytes. The vertical alignment of
      the chondrocytes within the scaffold is closely similar to that of articular
      cartilage.

PMID- 19094775
TI  - [Pay more attention to the prevention of iatrogenic injury].

PMID- 19094776
TI  - [Look into the future of the developing minimally invasive surgical skills from
      laparoscopic surgery].

PMID- 19094777
TI  - [Laparoscopic hepatectomy: concept and practice].

PMID- 19094778
TI  - [Laparoscopic resection of pancreatic islet cell tumors].
AB  - OBJECTIVE: To summarize the surgical technique and clinical experience of total
      laparoscopic resection of the pancreatic islet cell tumors. METHODS: From July
      2002 to December 2007, 30 cases including 12 males and 18 females were diagnosed
      as pancreatic islet cell tumor. There were at least one positive imaging
      examination of each patient preoperatively. The location of the tumors included 4
      in proximal pancreas and 26 in distal pancreas. RESULTS: The tumors were
      successfully found and removed in 28 cases and unsuccessfully located in the
      other 2 cases. The procedures included local resections in 13 cases and distal
      pancreatectomies in 15 cases (spleen reserved in 7 cases). The mean operation
      time was 165 min (range, 65 - 465 min). The mean blood loss was 145 ml (range, 50
      - 800 ml). Pancreatic leakage occurred in 3 cases, 2 of which were cured
      conservatively. And the other one were cured by endoscopic retrograde cannulation
      of the pancreatic duct. The mean postoperative hospital stay was 5.6 days (range,
      2 - 17 d). There were no conversions and death. After follow up of (14.3 +/-
      16.7) months (range, 4 - 62 months), there were no recurrences. CONCLUSION: Total
      laparoscopic resection is a safe and effective method for pancreatic islet cell
      tumors.

PMID- 19094779
TI  - [The application of laparoscopy in biliary reconstruction and rehabilitation
      after transection injury of biliary duct].
AB  - OBJECTIVE: To discuss the feasibility of biliary reconstruction and
      rehabilitation after transection injury of biliary duct by laparoscopy. METHODS:
      The clinical data of 24 cases receiving biliary reconstruction after transection
      injury of biliary duct by laparoscopy were analyzed retrospectively from August
      2002 to April 2008, including operation indications, contraindications, related
      operation skills and so on. In these 24 cases, the reasons of transection of
      biliary duct as followed: 15 cases were pancreaticoduodenectomy, 6 cases were
      resection of the choledochal cyst, 1 case was resection of high
      cholangiocarcinoma, 1 case was cholecystectomy and 1 case was resection of
      gastric cancer. RESULTS: Biliary reconstruction and rehabilitation was
      successfully completed in 24 cases by laparoscopy. There was 1 case of bile
      leakage and no duct stenosis complications. CONCLUSIONS: Biliary reconstruction
      and rehabilitation by laparoscopy was feasible and safe procedure, has a high
      successful rate, and deserves further clinical trials in hospitals.

PMID- 19094780
TI  - [Laparoscopic hepatectomy for hepatocellular carcinoma].
AB  - OBJECTIVE: To discuss the value of laparoscopic hepatectomy (LH) for
      hepatocellular carcinoma (HCC). METHODS: From April 2002 to December 2007, 123
      cases of HCC, included 82 males and 41 females, with a mean age of 53.8 years
      (range 31 - 69 years) underwent LH. RESULTS: Ninety-three cases underwent total
      laparoscopic hepatectomies (included regular hepatectomies in 52 cases). Twenty
      six cases underwent laparoscopy assisted hepatectomies (included regular
      hepatectomies in 12 cases). Four cases converted to open hepatectomies because of
      massive bleeding of hepatic vein. The operative time was (205.5 +/- 92.5) min
      (range 115 - 290 min). The median intraoperative blood loss was 250 ml (rang 100 
      1500 ml). The postoperative hospital stay was (5.8 +/- 1.6) days (range 3 - 15
      days). The biggest size of the resections was 18 cm x 16 cm x 12 cm. One patient
      died of gas embolism during the operation. Biliary fistula occurred in 5 cases
      and ascites in 8 cases postoperatively, which were cured for several days. By 4 -
      61 months of follow up, recurrence in liver occurred in 5 cases. There was no
      peritoneum and port metastasis. CONCLUSION: LH is a safe and feasible method for
      the treatment of HCC.

PMID- 19094781
TI  - [Hand-assisted laparoscopic hepatectomy for large liver cancer in 56 cases].
AB  - OBJECTIVE: To investigate the practical value of hand-assisted laparoscopic
      hepatectomy for large liver cancer in peripheral segments. METHODS: From March
      2004 to December 2007, 56 patients with large liver cancer underwent hand
      assisted laparoscopic hepatectomy including 53 cases of hepatocellular carcinoma,
      2 cases of cholangiocellular carcinoma, 1 case of hepatic metastatic squamous
      carcinoma. RESULTS: The operation procedures were completed safely in all
      patients including 27 left lateral segment hepatectomy, 6 left hemi-hepatectomy
      and 23 atypical right hepatectomy. Thirty-one cases with hepatic hilum blocking
      in the procedure and the mean time was 16.7 minutes. Mean surgical time was 105.3
      minutes. Mean blood loss was 97 ml. Mean gross tumor size was 8.6 cm. Mean
      excisional hepatic tissue volume was 10.5 cm. No serious postoperative
      complications occurred. Mean eating time was 2.1 days. The mean postoperative
      hospital stay was 7.3 days. CONCLUSION: Hand-assisted laparoscopic hepatectomy
      for large liver carcinoma is feasible and safe for selected patients.

PMID- 19094782
TI  - [Laparoscopic resection of submucosal tumors in gastric fundus].
AB  - OBJECTIVE: To investigate the feasibility and safety of extraluminal laparoscopic
      wedge resection (ELWR) in treating submucosal tumors in the gastric fundus.
      METHODS: Clinical data of 84 patients underwent ELWR for submucosal tumors in the
      gastric fundus between September 2000 and December 2006 were reviewed and
      analyzed retrospectively. The four-portal operation procedures were carried out
      as follows: localization of the tumor, dissection of the omentum, mobilization of
      the gastric fundus and the upper polar of spleen, exposure of ECJ, and resection
      of the gastric fundus with Endo GIA. RESULTS: The patients included 53 males and
      31 females, age ranged from 32 to 78 years (mean, 59 years). The mean tumor
      diameter was (4.2 +/- 1.3) cm. The distance from the tumor edge to the ECJ was
      1.1 - 3.0 cm. The operations were successful in all the 84 patients, with a mean
      operation time of (62.6 +/- 8.9) min and mean operative blood loss of (86.2 +/-
      8.1) ml. No apparent tumor focus was left. No operation was converted to open
      surgery, and no significant postoperative complications occurred. The mean post
      operative hospital stay was (5.6 +/- 0.5) days. The gastrointestinal function
      recovered within 36 h after operation in 66 cases (78.6%), and the patients
      returned to normal activity and restored oral feeding. The distance between the
      tumor and the resection margin was 0.7 - 2.5 cm from the ECJ [mean, (1.4 +/- 0.5)
      cm], and 2.5 - 6.0 cm from the other three sides [mean, (4.1 +/- 1.0) cm]. Of the
      84 cases, 29 cases were diagnosed with leiomyoma, 51 cases different types of
      stromal tumor and 4 cases neurofibroma. The mean follow-up duration was (51.0 +/-
      4.3) months, no recurrence or metastasis was found in the mean time. CONCLUSIONS:
      ELWR is a safe, simple and beneficial procedure for submucosal tumors in the
      gastric fundus, especially in the posterior wall near the ECJ. It avoids
      intraperitoneal infection, possible splenic injury and postoperative esophageal
      stenosis. In addition, the resection scope is not limited.

PMID- 19094783
TI  - [Changes of peritoneal free gastric cancer cells and its significance in patients
      after laparoscopic radical gastrectomy].
AB  - OBJECTIVE: To evaluate the safety and feasibility of laparoscopic radical
      gastrectomy on gastric cancer through comparison of peritoneal free gastric
      cancer cells detecting rates between laparoscopic and open radical gastrectomy.
      METHODS: Sixty-three patients received laparoscopic gastrectomy and 61 patients
      received open gastrectomy between April 2006 and June 2008 were included in this
      study. The peritoneal lavage fluid in those patients before and after the
      operation was collected. The cancer cell cytology and carcinoembryonic antigen
      (CEA) mRNA were detected with those samples. The relationship between peritoneal
      free gastric cancer cells and the area of cancer-invaded serosa was also
      observed. RESULTS: The positive rate of cytology in laparoscopic surgery was
      25.4% in the peritoneal fluid after the operation, while it was 29.5% in the open
      surgery, there was no significant difference between the two groups (P > 0.05).
      The positive rate of CEA mRNA in the peritoneal fluid after the operation in the
      laparoscopic group was 41.3%, and was 40.3% in the open group (P > 0.05). The
      area of cancer-invaded serosa in patients with positive cytology before and after
      the operation in the laparoscopic group was (16.2 +/- 2.2) cm(2), and it was
      (17.6 +/- 3.0) cm(2) in their counterparts in the open surgery group, while it
      was (5.3 +/- 0.8) cm(2) in patients with negative cytology before and after the
      operation. The area of cancer-invaded serosa was positively correlated with the
      positive rate of cytology(R(2) = 0.874, P = 0.000). CONCLUSIONS: Laparoscopic
      radical gastrectomy is not associated with a greater risk for peritoneal
      dissemination of cancer cells than the open technique.

PMID- 19094790
TI  - [The patterns and prognostic factors of abdominal lymph node metastasis in
      patients with the middle thoracic esophageal squamous cell carcinoma].
AB  - OBJECTIVE: To investigate the patterns of abdominal lymph node metastasis in
      patients with the middle thoracic esophageal squamous cell carcinoma and to
      evaluate the prognostic factors. METHODS: Three hundred and sixty-eight patients
      with the middle thoracic esophageal squamous cell carcinoma from January 1998 to
      January 2003 were reviewed. There were 289 male and 79 female patients. The age
      ranged from 38 to 79 years, with a mean of 56 years. Preoperative clinical stage
      was stage I to III, and all patients underwent Ivor-Lewis esophagectomy with two
      field lymphadenectomy. Follow-up was completed for all patients with a mean time
      of 68 months. Survival rate was calculated by Kaplan-Meier method. COX regression
      analysis was performed to identify risk prognostic factors. RESULTS: Abdominal
      lymph node metastasis occurred in 58 (15.8%) patients, with 36.2% (21/58) of them
      being in stage T1 or T2. Skipping abdominal lymph node metastasis was recognized
      in 13.8% (8/58) patients, with all of them being in stage T1 or T2. The overall 5
      year survival rate of patients with abdominal lymph node metastasis (10.3%) was
      lower than that of those with thoracic lymph node metastasis (18.3%). The
      prognosis of patients with distant abdominal lymph node metastasis was bad, and
      nobody could survive over 5 years.COX analysis showed that 5 or more positive
      nodes and distant abdominal node metastasis were independent risk factors of
      patients with abdominal lymph node metastasis. CONCLUSIONS: Abdominal lymph node
      metastasis in patients with the middle thoracic esophageal squamous cell
      carcinoma occurs frequently, and the surgery favorable for extensive abdominal
      lymph node dissection should be selected. The prognosis of patients with
      abdominal lymph node metastasis is poor, especially those with more positive
      nodes and distant abdominal node metastasis.

PMID- 19094792
TI  - [Long-term clinical result of posterior cruciate ligament retaining total knee
      arthroplasty: 15 years follow-up study].
AB  - OBJECTIVE: To evaluate the long-term clinical result and reason of failure of
      posterior cruciate ligament(PCL) preserved prosthesis in a 15 years of follow-up
      study. METHODS: A case series of 153 patients (178 knees) undergoing total knee
      arthroplasty (TKA) with PCL preserved prosthesis between September 1990 and March
      1992 in Center Medico-Chirurgical du Cedre was reported. All cases were evaluated
      with postoperative roentgenogram and Keen Society Clinical Scale. Measurement of
      X-ray included average hip knee ankle angle (HKA), deviation of HKA, alpha angle,
      beta angle, index of patella (AP/AT), proximal tibia angle (PTA), et al. RESULTS:
      Thirty-one patients died and 4 patients were lost at the time follow-up. And 118
      patients (125 knees) out of 153 patients were successfully followed-up. Fifteen
      years survival rate was 93.7%. And 11 knees were revised and the reasons were as
      follow: 9 aseptic loosening (7 knees with severe osteolysis, 2 knees with
      radiolucent line around tibial prosthesis); 1 recurvatum, 1 medial tibial plateau
      collapse. Postoperative score was 173 points. And 95.9% patients got good or
      excellent result. Comparing the clinical data of revised patients and un-revised
      patients, there were obvious difference between the following clinical data:
      varus and valgus angel of contralateral knee, beta angle of preoperative AP
      roentgenogram, preoperative and postoperative Knee Society Clinical Scale (P <
      0.05). CONCLUSIONS: PCL preserved prosthesis could recover the knee function to
      good or excellent result. Survival rate over 15 years is good. The way to
      sterilize the prosthesis could be the main reason for surgery failure. Few
      failures are related to PCL rupture. High wear rate and patellofemoral syndrome
      could be avoided by correct PCL and soft tissue balancing. Varus and valgus
      deformity of un-surgical knee and tibial varus deformity of surgical knee could
      be important factors for prosthesis failure.

PMID- 19094794
TI  - [Histologic study of local infiltration of spinal bone giant cell tumor and
      chordoma].
AB  - OBJECTIVE: To study the local infiltration length of spinal bone giant cell tumor
      and chordoma in various para-tumorous tissues. METHODS: Surgical specimens from 7
      patients with bone giant cell tumor and 10 patients with chordoma were divided
      into 6 groups: cortical bone group (CBG, para-tumorous tissue is bone cortex with
      periosteum), cartilage group (CG, para-tumorous tissues contain intervertebral
      disc, cartilage endplate and facet joint cartilage), trabecular bone group (TBG),
      paraspinal muscle tissue group (MTG), adipose tissue group (ATG) and scar tissue
      group (STG). Macroscopically margin (MSM) in the fresh specimens, histological
      margin (HLM) in the H&E sections and molecular margin (MCM) in the
      immunohistochemical staining sections were measured respectively. Three types of
      the margins of each group and MSM-HLMs, and MSM-MCMs among all groups were
      compared. RESULTS: Analysis of Variance comparing MSM, HLM and MCM within each
      group showed that there were significant differences in all groups (P < 0.05)
      except for CBG and CG. MSMs were significantly longer than HLMs and MCMs in TBG
      and MTG (P < 0.05), and MSMs were significantly longer than MCMs in ATG and STG
      (P < 0.05). MSM-HLMs and MSM-MCMs of TBG and ATG were significantly larger than
      those of CG and CBG. MSM-HLMs and MSM-MCMs of MTG and STG were significantly
      larger than those of CG; in addition, MSM-MCM of STG was significantly larger
      than CBG's. The maximum of tumor infiltration length in CBG, MTG, ATG and STG
      were 11.68 mm, 13.08 mm, 8.64 mm and 9.98 mm respectively. CONCLUSIONS: Each
      vertebra can be seen as a compartment, so total spondylectomy is an optimal
      procedure when bone giant cell tumor and chordoma localized in the compartment.
      To achieve a wide resection, a 1.3 cm wide margin in para-tumorous cancellous
      bone, a 1.5 cm wide margin in para-tumorous muscle and 1.0 cm wide margin in
      adipose tissues are necessary. First-time resection should be more aggressive and
      avoid tumor cell contamination. The surgical extent of salvage revision should
      contain para-tumorous scar tissue with the margin no less than 1.0 cm.

PMID- 19094795
TI  - [Preoperative enhanced three-dimensional spoiled gradient-recalled imaging for
      microvascular decompression of trigeminal neuralgia].
AB  - OBJECTIVE: To study the preoperative high resolution three-dimensional MR imaging
      of idiopathic trigeminal neuralgia, demonstrating the use in selection of
      patients and planning of the treatment. METHODS: The enhanced three-dimensional
      spoiled gradient-recalled imaging and three-dimensional MR angiography with 3-T
      MRI system were used to detect the anatomic relationship of neural and vascular
      structures at the trigeminal root entry zone preoperatively, surgical findings
      served as a reference to compare the MR visualization with the exact anatomic
      relations. RESULTS: Twenty-nine of 33 patients, who had the MRI positive vascular
      contact or compression, which was consistent to the symptom side, received the
      microvascular decompression (MVD). Surgical findings revealed neurovascular
      conflicts in all subjects, 27 of 29 (93%) were consistent to the imaging results,
      all the patients treated with MVD had the immediate complete pain relief.
      CONCLUSIONS: High-resolution MR imaging successfully demonstrated its usefulness
      in detecting the neurovascular contact at the trigeminal root entry zone, thereby
      facilitating the selection of patients who were most likely to benefit from MVD.

PMID- 19094796
TI  - [Bentall operation combined with total arch replacement and stented elephant
      trunk implantation for serious Debakey I aortic dissecting aneurysm].
AB  - OBJECTIVE: To summarize the clinical experience of Bentall operation combined
      with total arch replacement and stented elephant trunk implantation for serious
      Debakey I aortic dissecting aneurysm. METHODS: Twelve patients with serious
      Debakey I aortic dissecting aneurysm underwent surgical treatment from January
      2005 to December 2007. There were 10 male and 2 female with the mean age of (40.1
      +/- 9.5) years old. There were acute aortic dissection in 9 cases, chronic aortic
      dissection in 3 cases. The inner diameter of aorta was (5.3 +/- 1.8) cm. There
      were Marfan syndrome in 4 cases, aortic regurgitation in all cases, severely
      persistent chest pain in 9 cases, acute left heart failure in 8 cases, and
      cardiac tamponade in 4 cases. Bentall operations combined with total arch
      replacement and stented elephant trunk implantation were performed by using deep
      hypothermic circulatory arrest and antegrade selective cerebral perfusion in all
      cases. RESULTS: Urgent surgery underwent in 9 cases. The mean interval between
      the onset of aortic dissection and the accomplishment of surgery was (41.0 +/-
      15.9) hours. Cardiopulmonary bypass time was (191 +/- 26) min, average cross
      clamp time was (134 +/- 31) min, and average deep hypothermic circulatory arrest
      time was (50.0 +/- 14.5) min. One patient died in hospital. The time stayed in
      ICU was 3 to 27 d. Mental disorder in 6 cases, hemi-paralysis in 1 case,
      amputation in 1 case, hemorrhage of anastomosis in 1 case, hemorrhage of
      alimentary tract in 1 case, and pleural effusion in 4 cases were recorded. Eleven
      cases were followed-up for 8 weeks to 36 months. There were no bending of the
      stents and no obstruction in the vascular prosthesis.No re-operation was needed.
      One case died 6 months postoperatively. CONCLUSION: Bentall operation combined
      with total arch replacement and stented elephant trunk implantation is safe and
      effective for serious Debakey I aortic dissecting aneurysm, while good organs
      protection and consummate cardiopulmonary bypass were taken.

PMID- 19094797
TI  - [The primary evaluation of its safety and immune effect of NogoA vaccination for
      spinal cord injury].
AB  - OBJECTIVES: To prepare and purify NogoA vaccination for treatment of spinal cord
      injury. To study the safety and immune effect of this vaccination. METHODS:
      Artificial NogoA-13 polypeptide was coupled with KLH to improve the
      immunogenicity of vaccination. Sixty three-week-old Wistar female rats were
      divided into 3 groups randomly. Group A was immunized with NogoA vaccination,
      group B with incomplete freund's adjuvant + complete freund's adjuvant; group C
      with KLH. Rats received abdominal cavity immunization. The level of antibody and
      the binding capability were detected with ELISA. The safety of vaccination was
      evaluated by the incidence and severity of experimental autoimmune
      encephalomyelitis (EAE). RESULTS: The IgG antibody against the NogoA-13
      polypeptide had been detected with ELISA in group A. A value of serum presented
      regular gradient during multiple proportion dilution. In group B and C, no
      antibodies were detected. The statistical significant difference in A value was
      revealed between group A and B, C group. No statistical significant difference
      was found in A value between group B and group C and non-immunized negative
      control serum. The features of EAE were not found in the immunized rats.
      CONCLUSIONS: NogoA polypeptide vaccination can stimulate the antibody against the
      polypeptide. The immune effect of this vaccination is confirmed by binding
      reaction revealed in the ex vivo experiment. The good safety of vaccination is
      revealed by no features of EAE found in the immunized rats.

PMID- 19094798
TI  - [The in vitro differentiation and the variant expression of protein of bone
      marrow stromal stem cells when treating the spinal cord injury].
AB  - OBJECTIVE: To explore the differentiation and the variant expression of protein
      of the bone marrow stromal stem cells (BMSCs) when the BMSCs differentiated into
      the neuronal cells in the analogous micro-environment of spinal cord injury.
      METHODS: BMSCs were isolated from bone marrow of Wistar rats and labeled with
      PKH26 (control group), and then were cocultured with neural cells, which were
      isolated from the spinal cord of the fetal rats, in the same plate well (co
      culture group) or in the two-layer Petri well (two-layer group). Eight days
      later, the BMSCs were identified by immunofluorescence staining of NSE and GFAP
      respectively. The apparently changing proteins were analyzed by SELDI-TOF-MS
      while the BMSCs differentiated into neurons. RESULTS: Eight days after co
      culturing with neural cells in the same plate well or in the two-layer Petri
      well, BMSCs appeared more similar with neural cells. The immunofluorescence
      identification showed that, NSE and GFAP of which the BMSCs of the two-layer
      group expressed were obviously higher than control group (P < 0.05); and these
      two proteins of co-culture group were also obviously higher than the other two
      groups (P < 0.05). Five proteins in the co-culture group changed obviously as
      followed: TIP39_RAT and CALC_RAT were 5.360 and 2.807 times of that in the
      control group; INSL6_RAT, PNOC_RAT and PCSK1_RAT were 38.0, 49.9 and 43.8 percent
      of those in the control group. CONCLUSIONS: BMSCs could differentiate into neural
      cells in vitro, and the differentiation ratio of BMSCs in the co-culture group is
      higher than that of the two-layer group. Five proteins, including TIP39_RAT,
      CALC_RAT, INSL6_RAT, PNOC_RAT and PCSK1_RAT, are correlated closely to the
      mechanisms of which the BMSCs differentiated into neurons.

PMID- 19094805
TI  - [Screening of somatization disorder in primary health care. Results from a pilot
      study].
AB  - INTRODUCTION: There are no population based studies of Somatoform Disorders (SD)
      in Portugal, despite the fact that a high prevalence has been reported in other
      countries, mainly when less restrictive criteria are used for diagnosis. This
      study represents the first step to know the impact of this pathology in the
      community. AIMS: To evaluate the psychometric properties of a Portuguese version
      of SOMS-2 (Screening for Somatoform Disorders) in primary health care (PHC) and
      studying its relationship with depression and anxiety. METHOD: All persons
      attending an urban PHC unit aged 18 years or more and knowing how to read and
      write were invited to participate in this study undertaken during 2 days in
      January, 2007. All participants filled a socio-demographic questionnaire and a
      translated version of a screening instrument for Somatization Disorder (SD) (SOMS
      2), including a list of 53 somatic symptoms and 15 questions to evaluate the
      severity and presence of other somatoform disorders. A measure of anxiety and
      depression was also obtained using the Portuguese version of HADS (Hospital
      Anxiety and Depression Scale). RESULTS: The 122 participants, 16% out of the 760
      contacted, had on average 46.5 years (sd = 16.3) and 63% were woman. After
      applying criteria for frequency (> 10%) and discriminative power in terms of
      incapacity, 19 symptoms were included in the final scale. Using as standard the
      number and the specific symptoms for the presence of Somatization Disorder from
      the DSM-IV-TR, a cut-off point of at least 8 symptoms was estimated. The
      sensitivity and specificity were 94.1% and 89.5%, respectively. This cut off
      warranted 22.1% of individuals to be referred for further examination. The
      relative risk of anxiety and depression in a somatizer were 3.4 (95%CI: 2 to 6)
      and 4.3 (95%CI: 1.6 to 11.6), respectively. CONCLUSIONS: The results obtained
      with this Portuguese version of the SOMS-2 including 19 symptoms indicate it
      might be helpful for the screening of SD in PHC, though further clinical
      validation will be needed for establishing differential diagnosis.

PMID- 19094806
TI  - [Characterization of oncological disease: racional, objectives and methodology -
      perfil study].
AB  - Oncologic disease is one of the main causes of death in Portugal, as well as a
      high morbidity rate. Over the past few years, these diseases have been targeted
      with several strategies which aims at optimizing the use of available therapeutic
      and diagnostic options. Nevertheless, the amount of quantitative information
      available regarding the disease, patient profile, and treatment and monitoring
      practices is very low. In order to optimise the implementation of health policies
      specifically directed at oncologic diseases reliable and up-to-date information
      is needed, permitting optimisation and balancing of costs and benefits. The
      PERFIL national epidemiologic study is a multi-centre, retrospective cohort study
      which aims at evaluating the clinical practice regarding treatment of 6
      neoplasias -colorectal, gastric, breast, prostate, lung, and lymphoma, in
      Portugal, between 2003 and 2007. This study is based upon data collection from
      the clinical files of patients being followed in the participating centres from
      2003 to 2007. Qualitative evaluation (diagnosis and stage) was collected from the
      clinical records of all patients seen in each participating centre on a given
      month in each year from 2003 to 2007. The characterization of both patient
      profile and treatment and monitoring patterns will be based on a far-reaching
      analysis of 10,000 of those files, selected in a random and stratified sampling.
      This article describes the PERFIL study rationale, its objectives, and
      methodology.

PMID- 19094807
TI  - [Can we find predictive factors of postoperative vomiting after day surgery?].
AB  - A retrospective analyses of patients submitted to surgery on a day basis was made
      through our database. The goal of the study was to identify risk factors of
      postoperative vomiting associated to day surgery. 2115 patients operated between
      January 2003 and November 2004 on our day surgery unit were included. 70 patients
      (3,3%) suffered at least on episode of postoperative vomiting. Several factors
      were analysed: age, sex, surgical speciality, ASA physical status, anaesthetic
      technique and the duration of anesthesia. Chi-Square Test was used for testing
      each factor individually. Differences were considered significant when p <0,05.
      Logistic regression was then used to identify the multivariate association
      strength of these factors. The female sex (Odds ratio =4,94) and the duration of
      anesthesia when longer than 180 minutes (Odds ratio =8,13), had been associated
      to a higher incidence of postoperative vomiting, while loco-regional technique
      (Odds ratio = 0,15) and sedation with local anaesthesia (Odds ratio =0,09) had
      been associated with a lower incidence. Authors evidence the importance of the
      identification of postoperative vomiting risk factors that will allow us to
      establish better guidelines on postoperative nausea and vomiting prophylaxis in
      these patients and to improve the quality of our clinical care and the
      satisfaction of our patients.

PMID- 19094808
TI  - [Overweight and obesity - prevention in the school].
AB  - INTRODUCTION: The prevalence of the childhood obesity through the last decades is
      increasing, with significant comorbidities and major health consequences.
      Children's food habits are influenced by family, friends, school and the media.
      Successful interventions for preventing childhood obesity must include nutrition
      education, physical activity, school-based programs, family participation and
      counseling. AIMS: To evaluate the prevalence of overweight and obesity among
      children and adolescents in an urban area in Lisbon and to implement a school
      based program to prevent obesity. METHODOLOGY: A cross sectional study was
      performed in children and adolescents attending the public school in an urban
      area of Lisbon. Learning sessions regarding obesity were performed. FINDINGS: The
      study included 1875 children and adolescents, with ages between five and 17
      years. The overall prevalence rate found for overweight and obesity was 21% and
      9,5%, respectively. CONCLUSION: Obesity and overweight are important problems in
      children and adolescents. School-based programs can have an important role in
      preventing this disease.

PMID- 19094809
TI  - [Newborn with nonimmune hydrops fetalis - the experience of a tertiary center].
AB  - BACKGROUND AND AIMS: Nonimmune hydrops fetalis is a rare affection that can
      result from several disorders. Notwithstanding with the advances in the diagnosis
      and treatment, its morbidity and mortality are still very high. The purpose of
      this study was to characterize the newborn population with nonimmune hydrops
      fetalis admitted to our unit during the last ten years. METHODS: A descriptive
      review of the newborns with nonimmune fetalis hydrops admitted to the Neonatal
      Intensive Care Unit of Hospital de Sao Joao, between 1997 and 2006. Data on
      pregnancy, delivery, perinatal approach, etiological evaluation and outcome were
      collected. RESULTS: Nineteen neonates (9M/10F) with a median gestational age of
      32 weeks (26-39) and a median birth weight of 2695 g (884-4270) were studied.
      Sixteen (84%) were preterm. Antenatal diagnosis was made in fourteen (74%) cases,
      and two received in uterus treatment. C-section was performed in fourteen (74%)
      cases. Sixteen (84%) neonates needed resuscitation in the delivery room.
      Aetiological diagnosis was made in 89% (n = 17): cardiovascular (n = 5),
      haematological (n = 5), metabolic (n = 2), infectious (n = 2), chromosomal (n =
      1), lymphatic malformation (n = 1) and meconium peritonitis (n = 1). The median
      length of hospital stay was 17 days. Thirteen (68%) neonates were deceased.
      CONCLUSIONS: The occurrence and admission of newborns with nonimmune hydrops
      fetalis to our unit was rare. The aetiological diagnosis was made in 89% and
      mortality rate was 68%. The worse prognosis was related to preterm birth,
      anaemia, cardiac malformation, metabolic disorder, congenital infection and
      chromosomopathy. The prompt aetiological diagnosis and its proper ante and
      postnatal management are the most important steps to reduce the morbidity and
      mortality of this condition.

PMID- 19094810
TI  - [Nifedipine antihypertensive treatment effects in pre-eclampsia].
AB  - Literature analysis has been controversial about pre-eclampsia. It is known that
      not pregnant patients should be treated due cardiovascular benefits. However, the
      real benefits of antihypertensive treatment in pre-eclampsia were not
      demonstrated. Yet, there are many drugs that can be used for antihypertensive
      treatment in pregnancy. Calcium cannel blockers, particularly nifedipine, are
      used as a second line treatment. There are just a few evidences about nifedipine
      treatment in hypertension during pregnancy. Recently, researches were performed
      to evaluate the effects of nifedipine on maternal-fetal binomial, more safety,
      efficacy, and effectiveness were found using it. This literature review concludes
      that hypertension treatment only must be done in severe cases and emergency
      hypertensive. Therefore nifedipine can be used in antihypertensive treatment
      during pregnancy without serious complications.

PMID- 19094811
TI  - [Restless legs syndrome].
AB  - Restless legs syndrome (RLS) is a chronic sensorimotor disorder, with a negative
      impact in the quality of life and sleep architecture. Despite its reported high
      prevalence, remains under-recognized and under-treated. The diagnosis is based on
      the presence of four essential criteria, three supportive clinical features, and
      other three associated features. The primary or idiopathic RLS is the most common
      presentation form, but it is very important to exclude other RLS secondary forms
      and other differential diagnosis. The physiopathology of the idiopathic RLS
      remains unclear, however changes in the dopamine pathway have been proposed, and
      justifies the use of dopaminergic agents as first line treatment. Iron therapy,
      opioids, anti-epileptics (gabapentin) and benzodiazepines are others non
      dopaminergic options of treatment in selected patients.

PMID- 19094812
TI  - [Drug rash with eosinophilia and systemic symptoms (DRESS syndrome)].
AB  - Adverse cutaneous reactions to drugs are frequent, affecting from 2% to 3% of all
      hospitalized patients. But only about 2% of these cutaneous reactions are severe
      and seldom are fatal. The term drug hypersensitivity syndrome refers to a
      specific severe drug reaction, including skin rash, fever, lymph node
      enlargement, and single or multiple organ involvement. The cutaneous rash is
      usually morbilliform. The drugs associated with the syndrome are:
      anticonvulsants, ACE inhibitors, Beta-blockers, allopurinol and sulphonamides.
      The differential diagnosis includes maculopapular rash, exfoliative dermatitis,
      acute generalized exanthematous pustulosis and Sezary syndrome. The interval
      between the starting of drug therapy and the onset of cutaneous reactions may be
      at least one month, and therefore the implication of the drug in the aetiology
      may be subdiagnosed.

PMID- 19094813
TI  - [Basal-like carcinoma of the breast].
AB  - Breast cancer presents as a heterogeneous disease, not only for the clinic and
      histology, but also in genetic expression profile. Studies using cDNA microarrays
      have recently led to the re-classification of invasive breast carcinomas, based
      on their molecular signature, into three main groups: luminal; HER2 (Human
      Epidermal Receptor 2) overexpressing, and basal-like. Although the latter group
      is the least prevalent it is the most aggressive one, lacking a target based
      therapy, since their main characteristic is being negative for hormonal receptors
      or HER2. So, it is of paramount importance to try to unravel their histogenic
      origin and characterize their molecular and immunohistochemical profiles. EGFR
      (Epidermal Growth Factor Receptor), which is overexpressed in a high proportion
      of these carcinomas, is a potential therapeutic target, and clinical trials with
      inhibitors of its activity may represent important advances in basal-like breast
      carcinomas therapy.

PMID- 19094814
TI  - [Hypothyroidism and terminal renal failure in the neonatal period].
AB  - It has been described alterations of the thyroid function in patients with
      chronic renal disease without primary disease of the thyroid gland. Nevertheless
      primary hypothyroidism is more frequent in this population than in other non
      renal chronic disease. Authors report two cases of hypothyroidism diagnosed in
      infants with terminal renal failure in the neonatal period, secondary to renal
      hypoplasia / dysplasia, both in peritoneal dialysis programme. The diagnosis was
      made by elevated value of thyrotropin (TSH) on the metabolic screening test
      (TSH/PKU screening test) and confirmed later by measure of serum TSH, total
      triiodothyronine (T3), total thyroxine (T4), free triiodothyronine (FT3), free
      thyroxine (FT4) and thyroglobulin (TGB). It was also investigated antithyroid
      autoantibodies. Both infants initiated hormonal substitution with thyroxin, which
      have been suspended in one of them by two years of age when thyroid function was
      normal.

PMID- 19094815
TI  - [Cardiac arrest in the pediatric population].
AB  - A case of cardiac arrest in a ten year old child that was successfully
      resuscitated is here presented. The etiological investigation showed an
      Hypertrophic Cardiomyopathy (HCM). An Implantable Cardioverter Defibrillator
      (ICD) was placed for secondary profilaxy of Sudden Death (SD). Sudden Death in
      paediatric age is a rare accident with bad prognosis (survival with no sequel
      inferior to 5%) and with huge social impact. Hypertrophic Cardiomyopathy is a
      recognised cause of Sudden Death where prevention is possible. This report is
      important to enhance the question about the need and form of strategies to
      prevent sudden death of cardiac origin in pediatric age.

PMID- 19094816
TI  - [Post-malaria neurologic syndrome].
AB  - The neurologic symptoms in malaria are usually associated with a severe infection
      by Plasmodium falciparum. Less frequently, the presence of impaired
      consciousness, seizures and visual and auditory deficits is related with
      hypoglycemia (by malaria or quinine) or with the toxicity of anti-malarial drugs.
      In the last years, it was recognized a rare neurologic complication after the
      efficient treatment of Plasmodium falciparum malaria - post-malaria neurologic
      syndrome (PMNS). PMNS occurs days to weeks after the parasite clearance,
      presenting as an encephalopathy of variable severity. The pathogenic mechanisms
      involved in PMNS are not well understood, being admitted a possible immunological
      cause. We describe a case of a 61-year-old man presenting with a severe
      encephalopathy (delirium, cerebellar ataxia and ophthalmoparesis ), 2 days after
      complete recovery from Plasmodium falciparum malaria. Peripheral blood smears
      were repeatedly negative for malaria parasites. MRI during acute phase showed
      extensive multifocal white matter abnormalities. He was treated with high-dose
      methylprednisolone with complete resolution of neurological deficits. After 9
      months the MRI showed minimal residual lesions.

PMID- 19094818
TI  - Can metronidazole still be used for treatment of Clostridium difficile
      infections?

PMID- 19094819
TI  - Antimicrobial therapy for bone and joint infections.
AB  - Bone and joint infections present a major therapeutic dilemma for health care
      providers from different medical and surgical specialties. There is a conspicuous
      lack of strong data on epidemiologic findings, financial impact related to loss
      of work, and rehabilitation cost in the area of bone infections. This review
      outlines the antimicrobial options and duration of therapy for osteomyelitis,
      prostheses-associated orthopedic infections, and septic arthritis.

PMID- 19094820
TI  - Pharmacokinetics of antibiotics or antifungal drugs in intensive care units.
AB  - Intensive care unit (ICU) patients present several unusual pharmacokinetic (PK)
      characteristics compared with less seriously ill patients, including increased
      distribution volume and variable clearance. Interpatient PK variability is often
      considerable and can produce a wide range of values for PK parameters and major
      differences in drug exposure. These analyses have led to the development of
      simulation techniques and population PK models to assess dosing regimens in
      specific patient subsets. Plasma concentrations may frequently overestimate
      target-site concentrations and therefore clinical efficacy. The unbound drug
      concentration at the infection site should be preferred. Although renal
      replacement therapy techniques are commonly used in ICU patients, data concerning
      antibiotic dosing in this setting remain limited. Administration of antibacterial
      agents by continuous infusion is becoming a common technique to avoid undesirable
      high peak concentrations and low trough concentrations and to optimize PK
      pharmacodynamic indices.

PMID- 19094821
TI  - New antimicrobial agents for patients with Clostridium difficile infections.
AB  - Current drug treatment of Clostridium difficile infection (CDI) focuses on
      metronidazole and vancomycin. Early studies showed equivalence, but more recent
      reports indicate that oral vancomycin is preferred for serious CDI. Recent work
      has demonstrated a need for new drugs due to challenges with the NAP-1 strain,
      which appears to cause more refractory disease that is more likely to relapse.
      These two distinctive facets of treatment are the most challenging. This review
      discusses new agents in development: antibiotics, probiotics, immune response
      products, and agents to bind C. difficile toxins. None are likely to be more
      effective than oral vancomycin for acute infection. However, several may be as
      effective, without causing relapse or promoting unnecessary antibiotic use for
      multiple conditions. The greatest promise is with agents used to interrupt
      relapses. In this category the leading new agents appear to be antibiotics
      (rifaximin, nitazoxanide, difimicin, ramoplanin), toxin-binding agents
      (tolevamer), probiotics (Saccharomyces -boulardii and Lactobacillus ramosus), and
      immune agents (toxoid vaccine and hyperimmune globulin). The drugs that appear
      most promising based on recent trials are rifaximin, tolevamer, and difimicin,
      which appear promising for reducing relapses.

PMID- 19094822
TI  - Modern antifungal therapy for neutropenic fever.
AB  - Empirical antifungal therapy has been shown to decrease the number of documented
      fungal infections in the setting of persistent fever during neutropenia. For
      decades, amphotericin B deoxycholate has been considered the agent of choice for
      first-line therapy in this setting. New antifungal agents associated with less
      toxicity, including the lipid formulations of amphotericin, voriconazole, and
      caspofungin, are now available and are considered to be suitable alternative
      first-line agents. In order to ensure appropriate therapy, however, the clinician
      must consider not only the differences between these antifungals but also patient
      specific factors before initiating treatment.

PMID- 19094823
TI  - Japanese encephalitis: new vaccines.

PMID- 19094824
TI  - Tick-borne rickettsioses in America: unanswered questions and emerging diseases.
AB  - During most of the 20th century, Rickettsia rickettsii, the agent of Rocky
      Mountain spotted fever, was considered the only tick-borne rickettsia associated
      with human diseases in the Americas. This dogma suggested that the other
      characterized and noncharacterized rickettsiae isolated from ticks were not
      pathogenic to humans. This concept has been modified extensively in the past 10
      years with the identification of at least three additional rickettsial species
      that cause human tick-borne rickettsioses and that are prevalent in the Americas,
      including Rickettsia parkeri, Rickettsia massiliae, and Rickettsia africae.
      Moreover, the genetic variability of R. rickettsii and the milder forms of Rocky
      Mountain spotted fever reactivate the hypothesis that some circulating genotypes
      of R. rickettsii may be more virulent than others and may explain the wide
      variations in fatality rates of the disease.

PMID- 19094825
TI  - Travelers as a sentinel population: use of sentinel networks to inform pretravel
      and posttravel evaluation.
AB  - The establishment of collaborative sentinel surveillance networks specifically to
      monitor disease trends among travelers offers new options for evaluating travel
      health issues. These networks can inform pre- and posttravel patient management
      by providing complementary surveillance information, facilitating communication
      and collaboration between participating network sites, and enabling new
      analytical options for travel-related research. The two major multinational
      sentinel networks are TropNetEurop and GeoSentinel. Practical examples
      demonstrating their significant contributions to improved travel health
      information are discussed. Data obtained from studying health problems among
      travelers may also have significant benefits for local populations in resource
      limited countries. However, there are limitations of data collected by sentinel
      networks, so they should be considered as complementary tools and not relied on
      as an exclusive basis for evaluating health risks among travelers.

PMID- 19094826
TI  - Monitoring antimalarial drug efficacy: current challenges.
AB  - Access to effective antimalarial therapy has increased dramatically. As malaria
      endemic countries begin to use artemisinin-based combination therapy (ACT) to
      treat malaria, detecting the emergence and spread of resistance has become more
      complicated but also more urgent. Clinical efficacy studies may not be sensitive
      enough to detect the failure of a single component of combination therapy while
      standardized criteria for in vitro resistance and validated molecular markers are
      not yet available to many currently deployed drugs. This review discusses the
      challenges to various methods to monitor antimalarial drug resistance and
      proposes an integrated approach to the rapid detection and characterization of
      resistance to ACTs should it arise.

PMID- 19094827
TI  - Scrub typhus and rickettsial diseases in international travelers: a review.
AB  - Physicians caring for febrile returned travelers face the difficult task of
      recognizing the typical and atypical features of more than 16 known rickettsial
      diseases and separating these diseases from potentially serious nonrickettsial
      diseases. Currently available diagnostic tools are inadequate for timely
      diagnosis. This review summarizes the English-language literature concerning
      imported rickettsial diseases in international travelers and describes important
      clinical principles in diagnosis and treatment of these illnesses. -Travelers
      with imported rickettsial disease often become sick before or within a few days
      of return from an endemic region. Illness that begins more than 18 days after
      return is unlikely to be rickettsial in origin. The absence of a skin rash or
      exposure to a vector should not dissuade clinicians from considering the
      possibility of a rickettsial disease in a returned traveler. Finally, if empiric
      therapy does not result in defervescence within 48 hours, an alternative
      nonrickettsial illness should be strongly considered.

PMID- 19094829
TI  - Metabolic abnormalities associated with HIV infection and antiretroviral therapy.
AB  - Although noted early in the HIV epidemic, metabolic abnormalities came to
      prominence when potent combination antiretroviral therapy was introduced.
      Complications associated with HIV infection and antiretroviral therapy include
      cardiovascular disease, lipid disorders, glucose metabolism disorders, adipose
      tissue disorders, bone metabolism disorders, and lactic acidosis. Metabolic
      complications have driven the discovery of new agents and classes of
      antiretrovirals, and have shaped guidelines for the management of HIV infection.
      However, significant uncertainty remains about pathogenesis and management.
      Substantial complexity exists in the treatment of these disorders, illustrated by
      the complex drug-drug interactions between lipid-lowering agents and
      antiretroviral regimens. Several important new developments include the
      association of a higher risk of cardiovascular events with the discontinuation of
      antiretroviral therapy or use of specific drugs like abacavir and didanosine.
      This article reviews the current understanding of metabolic abnormalities
      associated with HIV and its treatment.

PMID- 19094828
TI  - Changes in the clinical epidemiology of HIV infection in the United States:
      implications for the clinician.
AB  - The HIV epidemic in the United States continues to affect racial/ethnic
      minorities disproportionately and is increasing among men who have sex with men.
      Late HIV diagnosis remains common. To reduce HIV transmission and facilitate
      early linkage to care and antiretroviral treatment, the Centers for Disease
      Control and Prevention recommends universal voluntary HIV screening for all
      persons ages 13 to 64 years in public and private care settings. Recent studies
      demonstrate dramatic reductions in morbidity and mortality with widespread use of
      highly active combination antiretroviral therapy (cART), and some document
      improved outcomes when cART is initiated with CD4 cell count >/= 350 cells/mm(3).
      As patients live longer, they are increasingly affected by chronic diseases,
      notably cardiovascular and renal disease, diabetes, and non-AIDS-defining
      cancers. Providers should ensure patients undertake preventive lifestyle changes
      (eg, smoking cessation, exercise, weight loss, dietary modification) and undergo
      recommended screening tests to reduce their risk for these important
      comorbidities.

PMID- 19094830
TI  - Allodynia as a complication of migraine: background and management.
AB  - Allodynia is a normal part of the untreated migraine attack in most people with
      episodic migraine and is prevalent in chronic migraine. The extent to which allo
      dynia contributes to the pain and disability of migraine attacks is unclear, as
      is its clinical importance. The presence of allodynia correlates with the
      severity and other features of migraine, including aura, migraine-associated
      symptoms, and motor symptoms. The development of allodynia is associated with
      resistance to triptan treatment. It is uncertain whether this treatment
      resistance is due to the accompanying increase in headache severity or whether
      the development of allo-dynia is the fundamental biologic event causing the new
      treatment-refractory state. Animal models support the relationship to allodynia.
      Intravenous ketorolac may be effective at treating migraine with allodynia
      several hours after the development of the throbbing pain, but prior treatment
      with opioid analgesics may confer treatment resistance. Occipital nerve blocks
      rapidly treat migraine pain and allodynia. Uncontrolled studies have successfully
      used dihydroergotamine to treat episodic and chronic migraine with allodynia.

PMID- 19094831
TI  - Headache and hormone replacement therapy in the postmenopausal woman.
AB  - Headache and migraine are common symptoms of the menopause, often associated with
      irregular periods, hot flashes, and night sweats. Perimenopausal women should
      routinely be asked about headache and migraine, so that they can be offered
      appropriate advice. If attacks are infrequent, it may be sufficient to optimize
      acute treatment strategies. Lifestyle changes, alone or combined with a
      nonprescription treatment such as isoflavones, may be considered, although
      evidence of efficacy is limited. In women with migraine and more severe menopause
      symptoms, continuous hormone replacement therapy should be considered, using a
      nonoral route and the lowest dose effective in controlling symptoms. For women
      who have contraindications to estrogen therapy or do not wish to use it,
      compounds that inhibit serotonin reuptake, such as venlafaxine, fluoxetine, and
      paroxetine, have all shown efficacy for the control of hot flashes and prevention
      of migraine. Gabapentin is another nonhormonal option that has clinical trial
      evidence of effectiveness in treating hot flashes and reducing the frequency and
      severity of migraine attacks. Although clonidine is licensed in several countries
      for migraine prophylaxis and treatment of vasomotor symptoms, any benefit from
      treatment is often offset by adverse events. There is evidence that hysterectomy
      can increase the frequency of migraine and menopause symptoms, with added
      morbidity and risk of mortality. Therapy should regularly be evaluated to assess
      its ongoing need, as hormonal triggers are self-limiting and abate after
      menopause.

PMID- 19094832
TI  - Is botulinum toxin useful in treating headache? Yes.
AB  - Recent scientific data support an effect of botulinum neurotoxin (BoNT) on pain
      and headache. BoNT was shown to affect the release of neurotransmitters that are
      important in pain transmission and in migraine pathogenesis. Data from both
      animal and clinical studies suggest that the toxin may have an analgesic effect
      that is independent from its effect on muscle tone. The high tolerability and
      long duration of action of the drug make it appealing as a potential prophylactic
      treatment for headache patients. Results of controlled trials on the efficacy of
      BoNT in the treatment of episodic migraine (EM) are mostly negative, although
      some subgroups of patients (eg, those with high attack frequency) may respond to
      the drug. Studies of patients with chronic daily headache have been inconclusive,
      although (as with the EM studies) specific subgroups of patients appear to
      benefit from the drug. BoNT is probably ineffective for the treatment of chronic
      tension-type headache. There are anecdotal reports on a positive effect of BoNT
      in patients with other types of headache (eg, nummular headache). Factors that
      may affect the response of patients to BoNT include headache characteristics,
      disease duration, the use of concurrent preventive medications, and the presence
      or absence of medication overuse. The authors' clinical experience shows that
      some headache patients benefit significantly from BoNT treatment. The challenge
      for future studies is to identify those patients who will best respond to the
      drug.

PMID- 19094833
TI  - Is botulinum toxin useful in treating headache? No.
AB  - The discrepancy between the widespread use of botulinum neurotoxin (BoNT) in
      managing headache and the supporting clinical evidence is unprecedented. No
      substance seems to have inspired more physicians and patients to undertake
      spirited treatment attempts. Tremendous treatment success in small, uncontrolled
      clinical trials has been repeatedly reported, but no substance that has been
      studied to an equal extent has so utterly failed to provide proof of effect in
      controlled clinical trials. Nevertheless, even though most randomized, controlled
      clinical trials have not met their defined primary outcome criterion, BoNT is
      still considered a promising treatment alternative for primary headache
      disorders. Experimental approaches to the pathophysiologic impact of BoNT on the
      perception of pain have been equally unsuccessful. Although most studies have
      been unable to find a direct antinociceptive effect in humans, some researchers
      continue to seek specific injection sites or injection techniques that may
      promise more successful results. Others look for a positive effect by narrowing
      the indications for BoNT to more homogenous symptoms or special patient
      subgroups. The results of randomized, controlled studies involving a total of
      3552 patients indicate that BoNT injection is probably ineffective for patients
      with migraine and chronic tension-type headache regardless of injection site,
      dosage, or injection regimen, and there is insufficient evidence to draw a
      conclusion about its effectiveness for the treatment of chronic daily headache or
      subforms. The lack of direct experimental or clinical trial evidence that BoNT
      has a direct antinociceptive effect in humans must be addressed before more
      trials are conducted, involving even more patients. Additional
      pathophysiologically oriented research is also needed to unravel the mechanisms
      of action of BoNT in human pain perception or, alternatively, to bring it all
      down to the placebo effect.

PMID- 19094834
TI  - Treatment of dural arteriovenous fistulas.
AB  - The treatment of a dural arteriovenous fistula (DAVF) depends on the severity of
      the symptoms, its angiographic characteristics, and the risk it presents for
      intracranial hemorrhage. In many instances, therapy may involve a combination of
      more than one modality. Low-risk DAVFs, either incidental or with minimal
      symptoms, can be treated conservatively (observation, blood pressure control,
      manual carotid compressions). If the patient does not tolerate the symptoms,
      definite or palliative treatment can be offered. All high-risk DAVFs (Borden
      Grade II or III) should receive treatment because they carry a high probability
      of intracranial hemorrhage or neurologic deterioration. For small, well
      circumscribed fistulas, radiosurgery can have excellent results, but thrombosis
      can occur many months after the treatment. For large DAVFs with severe symptoms
      (vision deterioration, ophthalmoplegia with diplopia, seizures, or neurologic
      deficit) or with high risk for hemorrhage (cortical venous drainage or venous
      varices), the first treatment option should be endovascular embolization. With
      the combination of modern materials and techniques, this procedure can yield a
      high rate of cure with minimal complications. In patients not amenable to
      embolization or after incomplete embolization, surgery should be considered if
      the DAVF is located in an easily accessible area, because of its immediate and
      definite results. Surgery can be facilitated by preoperative embolization of the
      fistula to reduce the arterial supply and minimize intraoperative bleeding.
      Radiosurgery can also be used adjunctively after embolization or surgery has
      significantly reduced the size of large DAVFs.

PMID- 19094835
TI  - Treatment of vestibular neuritis.
AB  - Vestibular neuritis is an acute peripheral vestibulopathy. It is thought to
      result from a reactivation of herpes simplex virus that affects the vestibular
      ganglion, vestibular nerve, labyrinth, or a combination of these. The symptoms
      are prolonged continuous vertigo, nausea and vomiting, and imbalance. In
      evaluating a patient with an acute vestibular syndrome, it is important not to
      miss a central cause, such as a brainstem or cerebellar stroke or hemorrhage,
      which could be life-threatening. Definitive central signs are not always present.
      Thus, any patient thought to have vestibular neuritis who has significant
      vascular risk factors should be evaluated for possible stroke. Most patients
      recover well from vestibular neuritis, even without treatment. Nonetheless,
      studies suggest that a course of oral steroids accelerates the recovery of
      vestibular function; whether steroids influence long-term outcome is less
      certain. Thus, until more data become available, it is reasonable to treat
      otherwise healthy individuals who present within 3 days of onset and to withhold
      steroids from those who are at higher risk of complications. Antiemetics and
      vestibular suppressants are useful acutely but should be withdrawn as soon as
      possible (preferably after the first several days), because their prolonged use
      may impede the process of central vestibular compensation. Early resumption of
      normal activity should be encouraged, to promote compensation. Directed
      vestibular rehabilitation therapy can further promote this process.

PMID- 19094836
TI  - Treatment of anti-Ma2/Ta paraneoplastic syndrome.
AB  - The paraneoplastic syndrome caused by Ma2/Ta antibodies alone (not in conjunction
      with Ma1 or Ma3 antibodies) varies in presentation from classic limbic
      encephalitis. The Ma2 syndrome may present with symptoms referable to the
      brainstem, diencephalon, and limbic system. These clinical symptoms are
      accompanied by MRI changes and abnormal electroencephalographic findings. It is
      important to recognize when the encephalitic syndrome is secondary to Ma2
      paraneoplastic antibodies, as the patients improve or stabilize most often when
      the underlying carcinoma is treated. Treatment of the paraneoplastic syndrome
      begins with recognition of the symptoms, such as memory impairment, seizures,
      sleep disturbances, bradykinesia or hypokinesia, and eye movement abnormalities.
      If a primary tumor is discovered during the workup, it should be removed and
      treated with the most up-to-date oncologic treatment available. In addition to
      oncologic treatment, the syndrome may be treated with an immunosuppressant
      regimen to optimize the neurologic outcome. Leaving the patient untreated will
      result in decline and eventual death from the cancer itself or from complications
      of the paraneoplastic syndrome.

PMID- 19094837
TI  - Acute demyelinating disorders of the central nervous system.
AB  - Acute demyelinating disorders of the central nervous system represent some of the
      most formidable management and therapeutic challenges to clinicians. These
      disorders include acute relapses of multiple sclerosis, neuromyelitis optica,
      acute disseminated encephalomyelitis, optic neuritis, and transverse myelitis.
      This paper summarizes clinical manifestations of these disorders, as well as
      treatment strategies. Currently, immunosuppression with corticosteroids for the
      acute events is the mainstay of treatment. Other experimental therapies, which
      may be effective in certain patients, are discussed.

PMID- 19094838
TI  - Pharmacologic management of brain edema.
AB  - Cerebral edema is an intrinsic response to a variety of structural and metabolic
      insults. It is a major contributing factor in the development of intracranial
      hypertension and brain herniation, underscoring the need for early identification
      through an integration of clinical and neuroimaging findings, followed by timely
      institution of measures to reduce brain edema and intracranial hypertension. The
      management of cerebral edema requires a comprehensive approach in which
      pharmacologic treatments play a central role. These include glucocorticoids,
      hyperosmolar agents, diuretics, and sedative-anesthetic agents. Basic,
      translational, and clinical studies are needed to further unravel mechanisms
      underlying brain edema, with the goal of identifying new treatment strategies.
      Promising targets include modulators of endothelial cell tight junction proteins
      and of aquaporin channel expression within the blood-brain barrier.

PMID- 19094839
TI  - Breast cancer and melanoma in the same pedigree.
AB  - This report is to document the occurrence of breast cancer and melanoma within
      either the same pedigree or the same patient and to make others aware of this
      association. A series of 52 patient pedigrees is presented from one clinical
      practice in which both breast cancer and melanoma were found over a 30-month
      period. It is suggested that formal pedigrees be obtained in addition to routine
      medical history questionnaires when either breast cancer or melanoma are
      encountered. It is further suggested that patients with either malignancy be
      screened for the other.

PMID- 19094840
TI  - Pentoxifylline: a drug with wide spectrum applications in dermatology.
AB  - Pentoxifylline (PTX) is a methylxanthine derivative with a variety of anti
      inflammatory effects. Currently, PTX is approved by the Food and Drug
      Administration for the treatment of intermittent claudication, but studies have
      shown that it has a variety of physiological effects at the cellular level, which
      may be important in treating a diverse group of diseases.

PMID- 19094841
TI  - Central centrifugal cicatricial alopecia: Superimposed tinea capitis as the
      etiology of chronic scalp pruritus.
AB  - We discuss a patient with central centrifugal cicatricial alopecia (CCCA) who
      developed severe scalp pruritus that was initially attributed to the cicatricial
      alopecia and ultimately diagnosed as tinea capitis. The rarity of severe pruritus
      in CCCA should prompt a search for a fungal infection in these patients.

PMID- 19094842
TI  - Pruritic urticarial papules and plaques of pregnancy wholly abated with one week
      twice daily application of fluticasone propionate lotion: a case report and
      review of the literature.
AB  - Pruritic urticarial papules and plaques of pregnancy (PUPPP) is among the most
      common dermatoses of pregnancy. Most reports of the effective treatment of PUPPP
      involve high potency topical corticosteroids or oral steroids. Many authorities
      have noted cases of PUPPP whose resolution followed parturition. A few have noted
      that PUPPP can arise and resolve the third trimester. A 36-year-old prima gravida
      at 38 weeks of gestation presented with a 2-week history of a pruritic papular
      abdominal eruption. She used fluticasone propionate 0.05 percent lotion twice a
      day. One week after starting this medication, the pruritus had resolved and the
      erythema/urticaria had abated; the pigmentary alteration had improved, but still
      remained. The PUPPP did not return after parturition. PUPPP can abate entirely
      during pregnancy. Fluticasone propionate 0.05 percent lotion, a class 5 (low
      medium potency) corticosteroid, has a benign side effect profile and should be
      considered for the treatment of PUPPP during pregnancy.

PMID- 19094843
TI  - CD4+/CD56+ Hematodermic neoplasm (plasmacytoid dendritic cell tumor).
AB  - A 60-year-old male presented with multiple, purplish-red, nodules and plaques.
      After a complete work-up, he was diagnosed with CD4+/CD56+ hematodermic neoplasm.
      We review the clinical, pathological, and immunohistochemical features of this
      disease. CD4+/CD56+ hematodermic neoplasm, which is also known as blastic natural
      killer-cell lymphoma, is a rare, aggressive neoplasm with a strong predilection
      for skin involvement.

PMID- 19094844
TI  - Lipoid proteinosis: report of three siblings.
AB  - Lipoid proteinosis is a very rare genodermatosis characterized by infiltration of
      hyaline material into the skin, oral cavity, larynx and internal organs. It
      usually presents in infancy with hoarseness. Although about 300 cases have been
      reported in the literature, the occurrence of the disease is rare in siblings. In
      this report we introduce three siblings with this disease.

PMID- 19094845
TI  - Treatment of gingival fibromas using CO2 laser and electrosurgery in a patient
      with tuberous sclerosis.
AB  - A 10-year-old boy with a history of tuberous sclerosis was sent for evaluation of
      numerous papules on his lower gum area. The parent was concerned that the lesions
      were interfering with oral hygiene. A diagnosis of oral fibromas was made and
      treatment options of gingivectomy or electrosurgery combined with carbon dioxide
      laser were described to the patient and his parent. Therapy with electrocautery
      and a pulsed carbon dioxide laser was decided on and utilized. We describe for
      the first time the combination of electrosurgery and carbon dioxide laser as a
      treatment method for oral fibromas. A short review of the literature regarding
      diagnosis and treatment is included with this report.

PMID- 19094846
TI  - Cutaneous metastasis of gastric adenocarcinoma: an exuberant and unusual clinical
      presentation.
AB  - There are different types of skin changes associated with internal malignancy.
      One type is the skin involvement as a result of cutaneous metastasis from an
      internal tumor. The skin is an uncommon site for distant metastasis; when it is
      present the most common sources are breast, lung, and colon. Metastasis generally
      occurs after an internal malignancy had been discovered and signifies
      disseminated disease with a poor prognosis. We report an exuberant and rare case
      of cutaneous metastasis from gastric adenocarcinoma as the first sign of this
      serious visceral cancer.

PMID- 19094847
TI  - A case of infliximab-induced psoriasis.
AB  - Anti-tumor necrosis factor (anti-TNF-alpha) are a group of new drugs able to
      inhibit the action of this cytokine. Although systemic side effects have been
      well described, cutaneous adverse reactions have not yet been clearly elucidated.
      The authors report a case of a 29-year-old man affected by Crohn disease and
      ankylosing spondylitis who developed psoriatic lesions after IV infusion of
      infliximab 5 mg/Kg. The patient underwent cyclosporine treatment after
      interruption of biological therapy, and had complete resolution of cutaneous
      lesions. The reason for this phenomenon is not clear, Obviously more studies are
      necessary to define more clearly this paradoxical reaction. In addition,
      dermatologists must be informed about this potential cutaneous adverse event.

PMID- 19094848
TI  - Sycosiform tinea barbae caused by Trichophyton rubrum.
AB  - Tinea barbae is an uncommon superficial dermatophyte infection of the beard and
      moustache areas. It was more frequently observed in the past, before single-use
      razors became available. In most cases, the zoophilic ectothrix Trichophyton
      mentagrophytes and Trichophyton verrucosum are responsible for this type of
      infection. Its clinical presentation is variable; it can mimic many other skin
      disorders such as sycosis, iododerma, contact dermatitis, perioral dermatitis,
      and actinomycosis. We report a case of tinea barbae caused by an uncommon agent
      Trichophyton rubrum, misdiagnosed as sycosis, and review the approach and
      management of the disease.

PMID- 19094849
TI  - A case of disseminate and recurrent infundibulofolliculitis responsive to
      treatment with topical steroids.
AB  - Disseminate and recurrent infundibulofolliculitis (DRIF) is an uncommon pruritic
      follicular eruption of unknown etiology that is predominantly seen in black men.
      This condition tends to affect the trunk and upper extremities and is usually
      unresponsive to local and systemic treatment. Recently, several investigators
      have reported successful treatment with isotretinoin. Herein, we report a case of
      a patient with disseminate and recurrent infundibulofolliculitis who was
      successfully treated with potent topical corticosteroids.

PMID- 19094850
TI  - Cutaneous metastasis of breast carcinoma mimicking malignant melanoma in scalp.
AB  - Cutaneous metastases of carcinoma of the breast may present a broad spectrum of
      clinical and histologic appearances. Pigmented metastases of a breast carcinoma
      have rarely been described in the literature and these metastases are usually
      located on the chest and abdominal wall close to the mastectomy scar. We report
      an unusual case of a cutaneous metastasis of carcinoma of the breast simulating
      malignant melanoma.

PMID- 19094851
TI  - Oculocutaneous albinism type 1A: a case report.
AB  - The term, oculocutaneous albinism (OCA), describes a group of inherited disorders
      of melanin biosynthesis that exhibits congenital hypopigmentation of ocular and
      cutaneous tissues. The clinical spectrum of OCA ranges from a complete lack of
      melanin pigmentation to mildly hypopigmented forms. OCA1A is the most severe type
      with a complete lack of melanin production throughout life; the milder forms
      OCA1B, OCA2, OCA3 and OCA4 show some pigment accumulation over time. Clinical
      manifestations include various degrees of congenital nystagmus, iris
      hypopigmentation and translucency, reduced pigmentation of the retinal pigment
      epithelium, foveal hypoplasia, reduced visual acuity and refractive errors, color
      vision impairment, and prominent photophobia. All four types of OCA are inherited
      as autosomal recessive disorders. At least four genes are responsible for the
      different types of the disease (TYR, OCA2, TYRP1, and MATP). Diagnosis is based
      on clinical findings of hypopigmentation of the skin and hair in addition to the
      characteristic ocular symptoms. Herein we present a case with OCA1A.

PMID- 19094853
TI  - The diagnostic importance of photosensitivity dermatoses in chronic alcoholism:
      report of two cases.
AB  - Many of the vitamin deficiency diseases have been almost completely eliminated in
      developed countries. Niacin deficiency is considered one of them. However, cases
      of pellagra are recently reported in West Europe, USA, Australia, and Japan in
      connection with chronic alcoholism, gastrointestinal malabsorption, and some
      medications. We report two cases of pellagra, manifesting as photosensitivity
      dermatoses with mental deterioration in chronic alcoholic abusers in the
      Mediterranean basin, the island of Crete in Greece. The report highlights the
      fact that all physicians should be alerted to photosensitivity dermatoses in
      alcoholics; early treatment with multiple vitamin therapy, including nicotinic
      acid should be initiated in these patients.

PMID- 19094852
TI  - Bortezomib-induced cutaneous lesions in multiple myeloma patients: a case report.
AB  - Proteasome inhibitors are emerging as a promising class of anti-cancer
      therapeutic agents. Bortezomib (PS341) is the first proteosome inhibitor with
      clinical significance. It acts by blocking vital functions of tumoral cells in
      myeloma, inducing apoptosis. Its toxicity is usually manageable. Gastrointestinal
      symptoms, peripheral neuropathy, neuropathic pain and thrombocytopenia are
      described as the most common side effects. We report on a case of cutaneous
      lesions induced by bortezomib in a patient with relapsed multiple myeloma (MM).

PMID- 19094854
TI  - Perioral pigmentation: what is your diagnosis?
AB  - Pigmented spots in the skin and mucosa (lentigines) can be found in various
      diseases called familial lentiginosis syndromes; Peutz-Jeghers syndrome (PJS) is
      one of them. It is characterized by the association of mucocutaneous melanin
      pigmentation and hamartomatous gastrointestinal polyps. Patients with PJS are at
      increased risk of intussusception and cancer development (gastrointestinal and
      non-gastrointestinal tumors). We present a 5-year-old girl with pigmented macules
      of perioral and perinasal skin, lips, and buccal mucosa and review lentiginoses
      and the surveillance of PJS.

PMID- 19094855
TI  - Case report: a case of pyoderma gangrenosum with intractable leg ulcers treated
      by allogeneic cultured dermal substitutes.
AB  - Pyoderma gangrenosum (PG) is an idiopathic, inflammatory, ulcerative disease of
      undetermined cause. Both topical and systemic treatments of corticosteroids and
      cyclosporine are commonly used for the ulcers of PG, but these ulcers are often
      intractable despite treatment. We employed allogeneic cultured dermal substitutes
      (CDS) in a patient with intractable ulcers due to PG. The CDS was prepared by
      cultured human fibroblasts on two-layered sponges of extracellular matrix such as
      hyaluronic acid and atelo-collagen. In the present case, re-epithelization and
      healthy granulation were induced by the CDS without increasing the dosage of
      systemic prednisolone. Then the subsequent autologous skin graft was successfully
      performed. This indicates that CDS is one of the useful tools for the treatment
      of intractable ulcers in patients with PG.

PMID- 19094856
TI  - Scar sarcoidosis with a 50-year interval between an accident and onset of
      lesions.
AB  - Cutaneous sarcoidosis has been reported to develop in scars. We report an unusual
      case of sarcoidal granuloma formation in scars that had been present for 50
      years.

PMID- 19094857
TI  - Yellow nails following hemodialysis in chronic renal failure: is it yellow nail
      syndrome or a variant?
AB  - Yellow nail syndrome (YNS) is triad of yellow nails, lymphedema, and respiratory
      tract involvement. The exact pathogenesis of nail changes in YNS is unknown. We
      present a case of yellow nails and localized lymphedema secondary to artificial
      AV fistula in a 55-year-old chronic renal failure patient on hemodialysis for 5
      years. To the best of our knowledge, this is the first case of yellow nail
      syndrome reported in association with artificial AV fistula.

PMID- 19094858
TI  - Navel melanoma: not always easy to detect, not always difficult to remove.
AB  - Melanoma diagnosis can be delayed when the tumor is present in areas that are
      poorly visualized. We present a peri-umbilical melanoma and discuss the use of Y
      plasty in this area.

PMID- 19094859
TI  - [Bacterial death and heteroresistance to antimicrobial agents].

PMID- 19094860
TI  - [Comparison of 3 methods for determining sensitivity to imipenem and meropenem in
      Acinetobacter baumannii with a carbapenem-heteroresistant phenotype].
AB  - INTRODUCTION: We assessed agreement among 3 assays for determining susceptibility
      to imipenem (IMP) and meropenem (MPM) of Acinetobacter baumannii (Ab)
      heteroresistant to carbapenems (Hr-CP). METHODS: Thirty Ab clinical isolates
      belonging to 6 clones (REP-PCR) were studied, in which IMP and MPM MICs were
      between < or = 1 and > or = 8 mg/l by Wider system. MICs determined by Wider were
      compared with those obtained by microdilution (MD) and E-test. Errors in the
      clinical category were determined considering MD as the reference method.
      RESULTS: Twenty-five Ab were Hr-CP (growth of resistant colonies within the
      inhibition area of disks and E-test strips). Agreement for the MICs (+/- 1log(2))
      in Hr-CP colonies was as follows: Wider vs. MD (96% IMP, 100% MPM), Wider vs. E
      test (50% IMP, 64% MPM), MD vs. E-test (64% IMP, 60% MPM). Major errors were not
      observed. Minor errors and moderate errors for IMP included Wider vs. MD (40% and
      0%), E-test vs. MD (40% and 12%), and disks vs. MD (36% and 8%). Agreement for
      the MICs considering colonies growing within the inhibition areas (E-test and
      disks) was Wider vs. E-test (8% IMP, 12% MPM), and MD vs. E-test (8% IMP and
      MPM). Major errors were not observed in this case either; minor errors and
      moderate errors for IMP were seen in E-test vs. MD (40% and 48%), and disks vs.
      MD (40% and 48%). CONCLUSION: Susceptibility testing methods based on
      microdilution (Wider system and MD) are not useful to detect subpopulations of Ab
      Hr-CP.

PMID- 19094861
TI  - [Comparative in vitro activity of daptomycin against gram-positive
      microorganisms: SENTRY surveillance program, Spain (2002-2006)].
AB  - INTRODUCTION AND OBJECTIVE: Daptomycin is a bactericidal lipopeptide antibiotic,
      active against gram-positive bacteria. In this study, the comparative in vitro
      activity of daptomycin and other antimicrobial agents against isolates recovered
      in 3 Spanish hospitals from 2002 to 2006 was determined as part of the
      international SENTRY antimicrobial resistance surveillance program. The possible
      therapeutic role of daptomycin is addressed in the light of Spanish
      susceptibility data. METHODS: Antimicrobial susceptibility testing was performed
      by the microdilution method with 1398 consecutively recovered gram-positive
      isolates. RESULTS: All the staphylococci (n = 1024), enterococci (n = 228), and
      streptococci (n = 146) studied were susceptible to daptomycin. The highest MIC
      values were 1, 4, and 0.5 microg/mL, respectively, regardless of methicillin,
      vancomycin, or penicillin resistance status. All Staphylococcus aureus isolates
      were also susceptible to vancomycin, teicoplanin, linezolid, and quinupristin
      dalfopristin. Coagulase-negative staphylococci were susceptible to vancomycin,
      linezolid, and quinupristin-dalfopristin. Only daptomycin and linezolid were
      active against all enterococcal isolates. In addition, vancomycin, teicoplanin,
      and ampicillin were fully active against Enterococcus faecalis. Daptomycin,
      vancomycin, teicoplanin, linezolid, and quinupristin-dalfopristin were active
      against all Streptococcus pyogenes, S. agalactiae, and S. viridans group
      isolates. The distribution of daptomycin MIC values in S. aureus and enterococci
      was homogeneously sustained along the 5-year study period. CONCLUSION: The
      sustained antimicrobial activity of daptomycin against staphylococci,
      enterococci, and streptococci in Spain makes this antibiotic an excellent
      therapeutic option in severe infection caused by gram-positive microorganisms,
      including those with multiresistance.

PMID- 19094863
TI  - Changes in liver-related hospital admissions and hospital mortality among HIV
      infected patients (1998 to 2005).
AB  - Liver-related disease has increased as a cause of hospitalization and in-hospital
      death in HIV-infected patients since the introduction of highly active
      antiretroviral therapy (HAART). Better clinical management of these diseases may
      contribute to decreasing their incidence. Admissions due to liver-related disease
      in HIV-infected patients in our institution increased from 2.9% in 1998-1999 to
      11.3% in 2004-2005 (P = 0.001). In-hospital deaths due to this cause increased
      from 2.7% in 1998-1999 to 26% in 2002-2003 (P = 0.02), with a subsequent decrease
      to 22% in 2004-2005. Hospitalization of HIV-infected patients for liver-related
      disease continues to increase, whereas the rate of in-hospital deaths from this
      cause appears to have changed since 2003.

PMID- 19094862
TI  - [What are we learning about Staphylococcus saprophyticus?].
AB  - INTRODUCTION: Staphylococcus saprophyticus is frequent cause of urinary tract
      infection in women; hence, it is important to know the epidemiology and
      antibiotic susceptibility of this microorganism. METHOD: A retrospective
      longitudinal study was performed in urine specimens from outpatients in our
      health area cultured in the Microbiology Laboratory of C.E. Arguelles (Madrid,
      Spain) over a 10-year period (1997-2006). RESULTS: Among 35,136 urine cultures
      with a significant count, we identified 331 S. saprophyticus (0.9%); 324 in women
      and 7 in men. Mean age of the infected patients was 32.7 years. A total of 83.9%
      of the strains were in women aged 15 to 44 years (37 women in this group were
      pregnant) and the largest numbers of isolates were found during the months of
      June and November. All S. saprophyticus strains were susceptible to vancomycin,
      rifampin, gentamicin and amoxicillin-clavulanic acid. Of note, there was a high
      percentage of resistance to erythromycin (37.7%) (96% consistent with the MSB
      phenotype) which has significantly increased since 1997 (P < 0.05); 1.5% were
      also resistant to clindamycin. Only 0.9% were resistant to fluorquinolones.
      Resistance to chloramphenicol, trimethoprim/sulfamethoxazole, and penicillin was
      3.9%, 6%, and 55.6%, respectively. Based on the 2006 CLSI guidelines, 45% of S.
      saprophyticus isolates were considered oxacillin-resistant. CONCLUSION: These
      results suggest the following: First, S. saprophyticus should be considered among
      agents causing urinary tract infection in women 15 to 44 years old, including
      pregnant women, particularly during spring and autumn. Second, cotrimoxazole may
      be an excellent option for treating cystitis in patients without risk factors.
      Third, almost half of S. saprophyticus strains were considered oxacillin
      resistant, thereby denying the benefit of treatment with oral beta-lactams in
      urinary tract infections. This is especially important in pregnant women, who
      should avoid trimethoprim/sulfamethoxazole and quinolones (FDA Group C), as well
      as fosfomycin, with in vitro resistance.

PMID- 19094864
TI  - [Trichophyton violaceum: an emerging pathogen].
AB  - Population changes taking place in recent years, such as more frequent travel to
      endemic areas, immigration, and international adoptions, have all contributed to
      a resurgence of certain pathogens in our geographical area. This is the case of
      Trichophyton violaceum. A retrospective review was made of all cases of
      superficial mycosis caused by T. violaceum in patients receiving in-hospital
      treatment during the years 2000 to 2006. This microorganism accounted for 18.5%
      of the 275 dermatophytes isolated during the above-mentioned period. In 96% of T.
      violaceum infections, the lesion manifested as tinea capitis, and all the
      patients were foreigners. We report in increase of tinea capitis caused by T.
      violaceum among pediatric patients that appears to be directly related to
      immigration.

PMID- 19094865
TI  - [Acute otitis media in the era of pneumococcal vaccination].
AB  - Acute otitis media (AOM) is one of the most common childhood diseases and the
      main reason for prescribing antibiotics in developed countries. Indiscriminate
      treatment of children with an inconclusive diagnosis has favored the development
      of resistance, and this has led to the creation of clinical guidelines to promote
      judicious antibiotic use. AOM has shown high rates of spontaneous resolution and
      minimal benefits from antibiotics; hence a policy of observation for 48-72 hours
      before initiating treatment is justified in many children. In recent years,
      attention has been focused on developing effective vaccines against the most
      common causative pathogens, Streptococcus pneumoniae and Haemophilus influenzae.
      The H. influenzae type b conjugate vaccine has little impact on AOM since most
      strains are nontypable. The 7-valent pneumococcal conjugate vaccine has an
      efficacy of 55% in AOM caused by vaccine serotypes, but replacement with
      nonvaccine serotypes and nontypable H. influenzae reduce the overall efficacy of
      the vaccine to 6-8%. An overall decrease of pneumococcal resistance to penicillin
      has been seen in vaccinated children, but there is a trend to an increase in
      antibiotic resistance in non-vaccine serotypes. High-dose amoxicillin is the
      treatment of choice for AOM, but the increase of H. influenzae in pneumococcal
      vaccinated children may require reconsideration of this recommendation in
      forthcoming guidelines.

PMID- 19094866
TI  - [Infectious spondylitis].
AB  - Vertebral osteomyelitis or spondylodiscitis is an uncommon, mainly hematogenous,
      disease that usually affects adults. The incidence of this condition has steadily
      risen in recent years because of increases in spine surgery and nosocomial
      bacteremia, aging of the population, and intravenous drug addiction. Pyogenic
      infection due to Staphylococcus aureus is the most frequent form of the disease,
      but tuberculosis and brucellosis are still common causes of spondylitis in Spain.
      The clinical presentation is nonspecific and the diagnosis is often delayed.
      Magnetic resonance imaging is the most sensitive radiologic technique for this
      disease. Blood cultures are often positive, but computed tomography-guided needle
      biopsy or surgical biopsy of the affected vertebra is sometimes required to
      achieve a microbiological diagnosis. Prolonged antibiotic therapy and
      occasionally surgery are essential for cure in most patients, and both factors
      have contributed to a reduction in the morbidity and mortality of the disease in
      recent years.

PMID- 19094867
TI  - [Infection associated with hemodialysis and peritoneal dialysis catheters].
AB  - Catheter-related infections in hemodialysis (HD) and peritoneal dialysis (PD) are
      one of the most common causes of morbidity and mortality in patients with end
      stage renal disease. Staphylococcus aureus in HD patients and S. aureus and
      Pseudomonas aeruginosa in PD patients are the most common causative organisms
      isolated. Currently, the diagnostic tests with highest yield in suspected
      catheter-related infection in HD patients have not been established, and tests
      used for central venous catheters (CVC) in general are applied. Management of the
      infected HD catheter and the use of antimicrobial therapy are similar to the
      measures used for other CVCs, with some specific recommendations. Peritonitis is
      the most severe complication in PD patients. Improving hygiene conditions in
      catheter insertion, treatment of S. aureus nasal carriers, regular treatment of
      the catheter's exit site, and antibiotic lock therapy have been associated with a
      reduction of infectious episodes in HD and PD patients.

PMID- 19094868
TI  - [Pruritus on the top and sole of the foot of a traveler returning from Central
      America].

PMID- 19094869
TI  - [Periungual lesions in a traveler returning from South America].

PMID- 19094870
TI  - [Evaluation of a latex agglutination test for serotyping Streptococcus
      pneumoniae].

PMID- 19094871
TI  - [Cryptogenic organizing pneumonia in an HIV-patient with good immunological
      status].

PMID- 19094872
TI  - [Nosocomial pneumonia due to community-acquired, methicillin-resistant, Panton
      Valentine-leukocidin-producing Staphylococcus aureus].

PMID- 19094873
TI  - [Aortic aneurysm and Coxiella burnetii].

PMID- 19094875
TI  - [Effect of polymorphisms of the cathecol-O-methyltransferase on schizophrenia
      risk in a Spanish population].
AB  - BACKGROUND AND OBJECTIVE: Cathecol-O-methyl transferase (COMT) is one of the most
      plausible susceptibility genes of schizophrenia risk. The main genetic variant
      (G158A or rs4680) studied is functional. It has been shown that G-A transition at
      COMT codon 158 makes COMT more thermolabile and less active at physiological
      temperature. Genetic variants in the P2 promoter have been suggested to cause
      alterations in brain COMT protein levels. A variant in the P2 promoter (-278A/G
      or rs1800706) has recently been associated with psychotic disorders. We studied
      whether polymorphisms in COMT (G158A, -278A/G) are risk factors for schizophrenia
      in a Spanish population. PATIENTS AND METHOD: 243 subjects diagnosed of
      schizophrenia and related disorders following the DSM-IV criteria and 291
      hospital-based controls participated in an association study. RESULTS: The
      heterozygotes for the COMT -278A/G polymorphism showed a 60% reduction in the
      schizophrenia risk (p = 0.009). No significant differences were observed between
      the other COMT genotypes or haplotypes in cases and controls. CONCLUSIONS: Our
      results suggest that the COMT -278A/G polymorphism may have a role in
      schizophrenia. The results are in agreement with recent findings in this field
      that indicate a minor influence of COMT G158A on schizophrenia risk and a greater
      importance of polymorphisms in the P2 promoter regions of COMT, such as -278A/G.

PMID- 19094876
TI  - [Diagnosis and secondary prevention measures in patients hospitalized for
      cerebral infarction in Spain. The DIAPRESIC study].
AB  - BACKGROUND AND OBJECTIVE: Data on implementation of stroke guidelines are scarce
      in Spain. We assessed the quality of diagnosis and prevention measures at
      discharge in patients admitted to hospital for acute cerebral infarction (ACI) in
      Spain. PATIENTS AND METHOD: Independent audit of clinical records on 1,448
      consecutive patients admitted to Spanish hospitals for an ACI, performed in a
      stratified-random sample of 30 public Spanish hospitals. The number of records
      evaluated per hospital was adjusted by hospital size. Information collected
      included demographic variables, cerebrovascular risk factors (CRF), family and
      personal history of cerebrovascular disease, prior cognitive impairment, subtype
      of infarction, use of functional and cognitive scales, supplementary
      investigations performed during hospital stay, recommendations, and treatments
      prescribed at discharge. RESULTS: No information about the ACI etiology was found
      in 46% of the clinical records. Information on prior vascular diseases was
      recorded in 69%. Information about pre-existing cognitive impairment was found
      only in 27%. The use of neurological scales was reported in only 21.1% of the
      cases. CRF information was observed in 99.2% of the cases. Antihypertensives and
      antidiabetic treatment were prescribed in 73.2% and 70% of hypertensives and
      diabetic patients, respectively. Lipid lowering drugs were prescribed in 57.3% of
      dislipemic patients. Antithrombotic treatment was prescribed in 82% of patients
      (antiplatelets 77.5%, oral anticoagulants 18.4%, combined therapy 4.1%).
      Information regarding CRF therapeutic goal attainments was scarcely registered.
      CONCLUSIONS: There is an inadequate adherence to guideline recommendations for
      the diagnosis and prevention of ACI in Spain. Particularly, the information
      included in the history regarding cerebrovascular disease, cognitive evaluation,
      characterization of cerebral infarction, and treatment and control of CRF should
      be improved.

PMID- 19094877
TI  - [Influence of pleural fluid red blood cell count on the misidentification of
      transudates].
AB  - BACKGROUND AND OBJECTIVE: Light's criteria misclassify a quarter of transudates
      as exudates. We assessed the influence of red blood cell counts on pleural
      lactate dehydrogenase (LDH) levels and, thereby, on the specificity of Light's
      criteria. PATIENTS AND METHOD: We retrospectively reviewed 1,312 consecutive
      patients with pleural effusion, of whom 1,014 were exudates and 298 transudates
      according to clinical criteria. The relationship between pleural erythrocytes and
      LDH using simple linear regression analysis, as well as the operating
      characteristics of Light's criteria, were assessed. Finally, a formula to correct
      pleural LDH levels, according to the erythrocyte count, was generated. RESULTS:
      There was a linear relationship between the pleural erythrocyte count and LDH
      levels (r = 0.44; p < 0.001). Light's criteria yielded 81% specificity in
      patients with pleural erythrocyte counts < or = 10.000 3 10(6)/l, as compared to
      61% in a group with a higher erythrocyte counts (p < 0.01). The application of
      the LDH formula enabled the correct reclassification of 24 of 64 (37%) false
      exudates. CONCLUSIONS: A high pleural erythrocyte count, through its influence on
      the LDH levels, may lead to a transudate being misclassified as an exudate after
      applying Light's criteria.

PMID- 19094878
TI  - [Pleural transudates misclassified with Light's criteria. Influence of pleural
      blood cells].

PMID- 19094879
TI  - [Lung cancer and COPD come together].

PMID- 19094880
TI  - [Postgraduate medical training in Spain (MIR): a proposal for the adaptation to
      the sanitary model requirements].

PMID- 19094881
TI  - [Chemical submission, epidemiology and some clues for the diagnosis].
AB  - The use of chemical substances to control people is not a new event. Indeed, it
      has been done for centuries. This practice has recenttly acquired a new dimension
      because of its association with sexual assaults and other type of crimes. The
      frequency of the association of the use of chemical substances with sexual
      assaults is behind the term SQ (drug facilitated sexual assauit). The Spaniish
      term foir this practice, Sumision Quimica, comes from the French one, Soumission
      Chimique, and has a wide meaning. In this review, the epidemiology of SQ is
      revised and an analysis of its main involved elements, namely the chemical, the
      victim and the assailant, is done. Chief clinical signs and clues for the
      toxicological doiagnosis are also appproached.

PMID- 19094882
TI  - [Caffeine, adenosine receptors, memory and Alzheimer disease].

PMID- 19094883
TI  - [Amniotic bands division: anesthetic implications].

PMID- 19094884
TI  - [Outcome of the coronary patients requiring mechanical ventilation].

PMID- 19094885
TI  - [Spanish version of the Severity of Dependence Scale (SDS)].

PMID- 19094886
TI  - [Acute acalculous cholecystitis due to Coxiella burnetii].

PMID- 19094887
TI  - [Hepatotoxicity related to escitalopram].

PMID- 19094888
TI  - [Fatal pneumococcal sepsis in patient with hidradenitis suppurative treated with
      infliximab].

PMID- 19094889
TI  - [Lupus pernio. Sarcoidosis].

PMID- 19094890
TI  - [Active middle ear implants. Introduction].

PMID- 19094891
TI  - [Physiology of bone conduction acoustic stimulation and the importance of high
      frequency bone conduction].
AB  - The phenomenon of bone-conducted sound transmission involves more than just
      vibration of the skull bones to induce movement of the labyrinthine fluid. This
      mechanical energy is known to be distributed through the outer, middle and inner
      ear and identifying the precise contribution of each of these parts to total
      conductance is difficult. Cochlear fluid inertia is the most important
      contributing factor to bone-conduction hearing, inertia of the ossicles plays a
      role in medium-frequency conduction, while cochlear wall compression plays a role
      in high frequencies.

PMID- 19094892
TI  - [How middle-ear implants work].
AB  - Middle-ear implants consist of a microphone, an audioprocessor, a battery, a
      receiver and a transducer. Transducers can be classified in three groups:
      piezoelectric, electromagnetic, and electromechanical. The middle ear transducer
      (MET) system (Otologics) is composed of an outer part that uses a multichannel
      digital acoustic signal processing system that transforms this acoustic signal
      into an electromagnetic stimulus. This system has fully implantable devices. The
      Vibrant Med El Soundbrige uses an electromagnetic design in which a floating mass
      transducer is crimped around the long process of the incus by a titanium strap,
      transmitting vibration to the ossicular chain.

PMID- 19094893
TI  - [Active middle-ear implants].
AB  - Active middle ear implants are classified as piezoelectric implants, which use
      the properties of piezoelectric materials. There are two types of piezoelectric
      implants: monomorphic and dimorphic; electromagnetic transduction uses a magnet,
      usually a rare earth magnet (e.g. samarium cobalt) and an energizing coil. This
      magnetic field causes the magnet to vibrate, which in turn, through the tympanic
      ossicular chain, causes movement of the cochlear fluids. Electromechanical
      transduction is a variation of electromagnetic transduction.

PMID- 19094894
TI  - [General indications of middle-ear implants].
AB  - Middle ear implants are indicated in bilateral neurosensorial hearing loss in the
      following situations: bilateral neurosensorial hearing loss with maximal
      thresholds of air conduction or air conduction within an established range. The
      differential threshold in frequencies of 500, 1,000, 2,000 and 4,000 Hz should
      not be above 10 dB in two or more of these frequencies. Minimal speech
      recognition must be 50% or more. Middle ear function and anatomy must be normal
      and there must be no evidence that hearing loss is of retrocochlear origin. Use
      of a hearing aid for at least 6 months in the ear receiving the implant must be
      proven to be unsatisfactory by a hearing test. Expectations must be realistic and
      vestibular alterations must be excluded.

PMID- 19094895
TI  - [Surgical implantation of the Med-El vibrant Soundbridge].
AB  - Surgical implantation of the Med-El Vibrant Soundbridge is, in the initial
      phases, similar to that of other otologic processes but differs in certain
      aspects that should be known. The surgical steps are as follows: incision,
      mastoidectomy, posterior tympanotomy, preparation of the implant bed, and
      placement of the device. The present article also describes the surgical
      procedure for placement of the device in the round window.

PMID- 19094896
TI  - [Surgical implantation of the fully implantable middle-ear hearing device].
AB  - The new fully implantable middle ear device (CARINA) is useful in sensorineural,
      conductive and mixed hearing loss. Surgical implantation of this device in the
      different types of hearing loss is similar in some aspects but differs in others.
      Consequently, we describe the surgical procedure in sensorineural and in
      conductive hearing loss separately.

PMID- 19094897
TI  - [Results of middle-ear implants].
AB  - The results of the various currently-available active middleear implants are
      discussed. These systems produce high satisfaction (above 85%) in patients with
      neurosensorial hearing loss. Round window stimulation systems provide excellent
      results in mixed and conductive hearing loss. Implant removal is required in less
      than 10% of patients.

PMID- 19094898
TI  - [The Esteem hearing implant by Envoy Medical].
AB  - The Esteem hearing implant by Envoy Medical is a fully implantable system that
      uses piezoelectric transducers. This device uses the eardrum as the microphone.
      The mechanical signal is detected by a piezoelectric transducer at the head of
      the incus (the sensor) and converted to an electrical signal that is amplified,
      filtered, and converted back to a vibratory signal. The processed vibratory
      signal is then delivered by another piezoelectric transducer (the driver) to the
      stapes capitulum.

PMID- 19094899
TI  - [Clinical impact of FDG-PET in patients with suspected recurrent ovarian cancer].
AB  - AIM: To evaluate the efficacy and clinical impact of FDG-PET in patients with
      suspected recurrent ovarian cancer. METHODS: Between October 2001 and October
      2006, we retrospectively studied 49 FDG-PET performed in 40 women (age: 52.4 +/-
      12.2 years) with ovarian cancer, who had suspicion of recurrent disease by
      positive morphologic imaging tests (MIT) or increased tumour markers and negative
      MIT. All patients underwent whole body FDG-PET after the injection of 370-434 MBq
      of (18)FDG. The results were confirmed by histology in 31 cases, and by clinical
      radiological follow-up in 18. RESULTS: Prevalence of disease was 79.6 %. We
      obtained a global sensitivity and positive predictive value of 87.2 % and 87.2 %,
      and an accuracy of 79.6 %. Results led to a change in the patient's management in
      25 cases (51 %). Subgroup results were: Sensitivity of 81.8 % in patients with
      increased tumour markers and negative MIT, and 89.3 % in patients with operable
      malignant lesions. CONCLUSIONS: FDG-PET has high sensitivity and clinical impact
      in patients with suspicion of recurrent ovarian cancer. Better results were
      obtained in patients with increased tumour markers and negative MIT.

PMID- 19094900
TI  - [Calculation of the left ventricular ejection fraction. Comparison between 4
      different instruments].
AB  - AIM: The aim of this study was to analyse the relationship between left
      ventricular ejection fractions (EF) obtained using four different instruments.
      MATERIAL AND METHODS: Eighty-five EF values were analysed. Gated acquisition was
      performed with the same gammacamera (SOPHA) using 99mTc-labelled red cells. Each
      EF was obtained using four processing systems: NXT (SOPHA), Entegra (Gems),
      Odyssey (Philips) and Esoft (Siemens), always working in automated mode. The
      paired student's t-test, Spearman correlation and Bland-Altman analysis were used
      to compare methods, and Deming regression was applied. RESULTS: Mean values and
      standard deviations for each program were: NXT: 61 +/- 9; Entegra: 60 +/- 10;
      Odyssey: 60 +/- 9; Esoft: 60 +/- 10. Although no significant differences were
      found as a whole and the values were linearly related, the methods are not
      interchangeable. CONCLUSIONS: The same program should be used in the follow-up of
      each patient, which is now easily achievable by means of the DICOM standard.

PMID- 19094901
TI  - [In-transit sentinel lymph nodes in malignant melanoma. What is their
      importance?].
AB  - The sentinel lymph node (SLN) is the first node in a lymph node basin to receive
      direct drainage from the primary tumour. However, in some cases,
      lymphoscintigraphy images demonstrate the presence of lymph nodes located in the
      area between the primary tumour and the first regional lymph node basin. These
      nodes are called in-transit nodes and have to be considered SLNs as well. AIM: It
      was to determine the incidence and location of in-transit SLNs in patients with
      malignant melanoma and to evaluate whether it is necessary to harvest them.
      METHOD. Nine hundred patients with malignant melanoma were included.
      Lymphoscintigraphy was performed on the day before surgery following intradermal
      injection of 74-111 MBq of 99mTc-Nanocolloid in four doses around the primary
      lesion or the biopsy scar. RESULTS: The presence of in-transit SLNs was revealed
      in 80 patients. During surgery, in-transit SLNs were identified and excised in
      all but 3 patients (96.2 %). Metastatic cell deposits were identified in these in
      transit SLNs in 15 patients (19.4 %), with 4 patients with no tumour involvement
      of the regional lymph node basin. CONCLUSIONS: Lymphoscintigraphy is mandatory in
      the location of in-transit SLNs. Moreover, although the incidence of these nodes
      is relatively low in malignant melanoma, the presence of metastatic cells in
      these in-transit SLNs reaches a significant percentage. Therefore, excision of in
      transit SLNs is necessary in all cases.

PMID- 19094902
TI  - [Potential use of bone marrow scintigraphy in suspected prosthetic hip infection
      evaluated with 99mTc-HMPAO-leukocytes].
AB  - AIM: To evaluate the usefulness of (99m)Tc-Sulphur colloid when combined with
      leukocyte scintigraphy in suspected prosthetic hip infection, comparing the
      results with information from (99m)Tc-HMPAO-leukocyte scintigraphy alone.
      MATERIALS AND METHODS: Seventy patients (42 women, 28 men; mean age 68 +/- 13
      years) with painful hip prostheses and suspicion of infection were evaluated
      prospectively. All patients had bone scintigraphy, (99m)Tc-HMPAO-labelled white
      blood cell scintigraphy and (99m)Tc-Sulphur colloid bone marrow scintigraphy. ESR
      and CRP levels were measured in all patients. The final diagnosis was made with
      microbiological findings or by clinical follow up of at least 12 months. RESULTS:
      Infections were diagnosed in 12 of the 70 patients (3 coagulase-negative
      Staphylococcus, 2 Staphylococcus aureus, 2 Staphylococcus epidermidis, 2
      enterococcus and 3 polymicrobial agents). ESR and CRP values were higher in
      patients with infection than in patients without infection (51.8 +/- 29.4 vs.
      25.4 +/- 16.4 and 2.8 +/- 2.2 vs. 1.1 +/- 1.3, respectively; p < 0.05). Bone
      scintigraphy did not show a characteristic pattern to differentiate infection
      from aseptic loosening. The pool phase of the bone scintigraphy was positive in
      only 3/12 patients with infection (25 %). Sensitivity and specificity of the
      leukocyte scintigraphy was 83 % and 57 %, respectively. When the results of the
      bone marrow scintigraphy were added, these values increased to 92 % and 98 %,
      respectively. CONCLUSION: Performing bone marrow scintigraphy significantly
      improves results when compared with leukocyte scintigraphy alone in the diagnosis
      of infected hip prostheses. Bone scintigraphy did not help to differentiate
      aseptic loosening from infection in this series.

PMID- 19094903
TI  - [Application of the ROLL technique in a case of bilateral multifocal breast
      cancer].
AB  - The increasing number of non-palpable breast lesions and the trend to perform
      less aggressive surgical procedures have prompted the development of radioguided
      surgery in breast lesions, alone (ROLL) or with sentinel node detection. We
      present a 55-year-old woman with four mammary lesions diagnosed by magnetic
      resonance. The ROLL technique allowed not only their characterisation but also
      the study of the lymphatic drainage of malignant lesions. Moreover, it was useful
      as a guide for surgical biopsy of the benign lesions. The combination of
      different colloid size allowed an accurate study of each lesion and avoided
      radical surgery. The applications of radioguided surgery are ever increasing.
      Individualisation of each indication will benefit a greater number of patients.

PMID- 19094904
TI  - [Tuberculosis in an FDG PET-TC study in a patient with suspected tumour
      recurrence of a pulmonary neoplasm].

PMID- 19094905
TI  - [Metastasis of clear-cell renal carcinoma in skeletal muscle].

PMID- 19094906
TI  - [Usefulness of bone scintigraphy in melorheostosis].

PMID- 19094908
TI  - [Iterative tomographic reconstruction].

PMID- 19094909
TI  - [Authorized specifications for human use in clinical practice of
      radiopharmaceuticals composed of iobenguane (123I) marketed in Spain].
AB  - This article details the specifications authorised for human use in the clinical
      practice for the radiopharmaceutical products composed of iobenguane ((123)I)
      marketed in Spain.

PMID- 19094912
TI  - Influenza vaccination coverage in England, 2000-2008.

PMID- 19094913
TI  - Cohort study of an outbreak of viral gastroenteritis in a nursing home for
      elderly, Majorca, Spain, February 2008.
AB  - An outbreak of acute gastroenteritis occurred in a nursing home for elderly in
      Majorca between 4 and 23 February 2008. To know its aetiology and mechanism of
      transmission a retrospective cohort study was conducted with a fixed cohort
      including 146 people (96 residents and 50 employees). The data were collected
      from clinical histories and through a survey by questionnaire. In total 71 cases
      were identified (53 residents, 18 employees), corresponding to an overall attack
      rate (AR) of 48.6%.

PMID- 19094914
TI  - Tuberculosis outbreak associated with a mosque: challenges of large scale contact
      tracing.
AB  - In this report, we describe the investigation and management of an outbreak of TB
      associated with a mosque in Scotland, and consider the implications of large
      scale TB contact tracing. The screening of casual contacts in this setting was
      complex and time-consuming with a low detection rate.

PMID- 19094915
TI  - A food-borne outbreak of cryptosporidiosis among guests and staff at a hotel
      restaurant in Stockholm county, Sweden, September 2008.
AB  - In September 2008, 21 cases of cryptosporidiosis occurred among guests and staff
      at a wedding reception in a hotel restaurant in Stockholm county, Sweden. The
      most probable source of the outbreak was bearnaise sauce containing chopped fresh
      parsley.

PMID- 19094916
TI  - Investigations and control measures following a case of inhalation anthrax in
      East London in a drum maker and drummer, October 2008.
AB  - The patient is believed to have acquired the infection from making animal hide
      drums. Environmental investigations identified one drum and two pieces of animal
      skins contaminated with anthrax spores.

PMID- 19094918
TI  - Cluster of imported malaria from Gambia in Finland--travellers do not listen to
      given advice.
AB  - Twelve Finnish tourists contracted falciparum malaria from Gambia in the period
      between 3 and 27 November 2008. None of them had used adequate malaria
      chemoprophylaxis.

PMID- 19094917
TI  - European cluster of imported falciparum malaria from Gambia.
AB  - A cluster of 56 patients returning from Gambia with falciparum malaria has been
      noted in several countries of the European Union since September this year.
      TropNetEurop, the European Network on Imported Infectious Disease Surveillance,
      collected and reported the cases. Lack of awareness and, consequently, of
      prophylactic measures against malaria were apparent in the majority of patients.

PMID- 19094919
TI  - Denmark: botulism in an infant or infant botulism?
AB  - A 4.5 months old, previously healthy Danish girl was admitted to a paediatric
      department after six days of passive behaviour and weak suck. Over the next days
      she became increasingly weak, developed bilateral ptosis, the muscle stretch
      reflexes were lost, and mydriasis with slow pupillary responses was noted.
      Botulism was suspected and confirmed by testing of patient serum in a bioassay.
      The condition of the patient improved following administration of botulism
      antiserum. The clinical picture was suggestive of intestinal (infant) botulism.
      However, botulism acquired from consumption of food with preformed neurotoxin
      could not be excluded.

PMID- 19094920
TI  - Malaria in travellers to Gambia.
AB  - Malaria incidence is reportedly declining steadily in many parts of the world,
      including in at least several African countries. The incidence of imported
      malaria is also declining in a number of European countries. However, incidence
      rates in travellers, both European tourists and the so called VFR (visiting
      friends and relatives) are difficult to estimate, due to problems with the
      numerator (many cases are not reported) and more importantly with the
      denominator, for which the information is generally lacking. An exception in the
      European Union is the United Kingdom (UK), where the International Passenger
      Survey provides a reliable denominator on the number of travellers to the
      different countries, duration of stay and reason for travel.

PMID- 19094923
TI  - [Epidemiology of osteoporosis].
AB  - Osteoporosis leads to fragility fractures. Fracture incidence increases after the
      menopause among women and with age in both genders. More than 40 % of women will
      sustain at least one fragility fracture after the age of 50. Many risk factors
      have been described, including age, familial history of fracture, low bone
      mineral density, personal history of fracture, smoking and low body mass index.
      Fracture incidence is increasing worldwide, owing to population aging. Hip and
      vertebral fractures are associated with increased mortality and morbidity. Costs
      related to fragility fractures represent a significant burden for health care
      systems.

PMID- 19094921
TI  - Adaptive strategies of African horse sickness virus to facilitate vector
      transmission.
AB  - African horse sickness virus (AHSV) is an orbivirus that is usually transmitted
      between its equid hosts by adult Culicoides midges. In this article, we review
      the ways in which AHSV may have adapted to this mode of transmission. The AHSV
      particle can be modified by the pH or proteolytic enzymes of its immediate
      environment, altering its ability to infect different cell types. The degree of
      pathogenesis in the host and vector may also represent adaptations maximising the
      likelihood of successful vectorial transmission. However, speculation upon
      several adaptations for vectorial transmission is based upon research on related
      viruses such as bluetongue virus (BTV), and further direct studies of AHSV are
      required in order to improve our understanding of this important virus.

PMID- 19094922
TI  - Neutrophils as one of the major haptoglobin sources in mastitis affected milk.
AB  - The antioxidant haptoglobin (Hp) is an acute-phase protein responsive to
      infectious and inflammatory diseases. Hp and somatic cell counts (SCC) are
      sharply elevated in bovine milk following intramammary administration of
      endotoxin or bacteria. However, the sources of milk Hp responsible for such
      increases are not fully understood. The purpose of this study was to define the
      source of milk Hp from dairy cows with naturally occurring mastitis. Quarter milk
      samples selected from 50 dairy cows were separated into four groups according to
      SCC as group A: < 100 (n = 19); B: 100-200 (n = 10); C: 201-500 (n = 10); and D:
      > 500 x 10(3) (n = 11) cells/mL. Our results reveal that milk Hp concentrations
      were correlated with SCC (r = 0.742; P < 0.01), and concentrations in group D
      were approximately 10-fold higher than in group A. Reverse transcriptase
      polymerase chain reaction (RT-PCR) analysis indicates that the milk somatic cells
      from group D were not only capable of synthesizing Hp but could also markedly
      increase Hp mRNA expression. Western blot, immunocytochemistry, double confocal
      immunofluorescence, and Hp releasing experiments demonstrate that neutrophils
      were associated with the biosynthesis and release of Hp in milk. It further shows
      that Hp was significantly elevated in the epithelium of mammary gland tissue with
      mastitis and was also expressed in the cultured mammary epithelial cells. We
      propose that neutrophils and epithelial cells may play an essential role in
      elevating milk Hp in addition to previous suggestions that Hp may be derived from
      mammary tissues and circulation.

PMID- 19094924
TI  - [Pathways regulating bone formation: a complex network].
AB  - Bone tissue undergoes permanent remodeling based on the coupled activity of
      osteoclasts resorbing old bone and osteoblasts forming a new matrix. The latter
      are considered as the main target of remodeling control pathways. Indeed, they
      have the full control of osteoclastogenesis through RANK-L / osteoprotegerin, the
      most critical pathway in the balance between bone formation and resorption. They
      also are under the effects of numerous transcription factors, especially members
      of the AP1 complex as well as the canonic Wnt - betacatenin pathway. Most bone
      tissue pathologies are mediated by alterations of these remodeling control
      pathways. Therefore, lots of efforts are made to modulate these factors which are
      very interesting potential therapeutic targets.

PMID- 19094925
TI  - [The challenges of the bone micro-architecture].
AB  - Osteoporosis is a bone disorder that leads to increased fracture risk. It was
      defined by the World Health Organisation as a decrease of bone mass and a
      deterioration of bone quality. In clinical practice, the diagnosis of
      osteoporosis is based on bone mineral density (BMD) measurements assessed by dual
      energy X-ray absorptiometry. However, BMD assessment is not the only factor that
      influences bone strength. The main objective is that clinicians can use a
      combination of risk factors that are easily assessable, for a better prediction
      of osteoporosis risk fracture. Bone strength reflects both bone density and bone
      quality. One of the most important determinants of bone quality is the trabecular
      bone micro-architecture as suggested by the definition of osteoporosis. Moreover,
      various studies have concluded to the potential clinical interest of the bone
      micro-architecture. The aim of this article was to review the challenges of bone
      micro-architecture, characterization tools (morphological analysis, topology,
      texture) and imaging techniques (X-ray imaging, scanning and MRI) to assess
      trabecular bone micro-architecture.

PMID- 19094926
TI  - [Daily clinical practice: Biological testing in osteoporosis].
AB  - Although biological testing has nothing to do with the diagnosis of osteoporosis,
      it can help the physician to: 1) identify secondary causes of low bone mass
      and/or fracture. There is however currently no consensus to define the
      biochemical parameters to be measured in this case. The cost-effectiveness of the
      biological evaluation, that is, measuring a minimum of parameters to detect a
      maximum of anomalies needs to be considered. Most experts agree that malignancy
      and especially a myeloma should be ruled out, and that an evaluation of
      calcium/phosphorus metabolism including the measurement of serum calcium,
      phosphate, PTH and 25 hydroxy-vitamin D should be performed. This allows to
      detect many anomalies including two very frequent conditions, primary
      hyperparathyroidism and vitamin D deficiency. Note however that complementary
      testing is generally needed to identify other diseases; 2) evaluate efficacy and
      observance of some osteoporosis treatments especially oral bisphosphonates. In
      this case, the evolution of the blood or urine level of some markers of bone
      turnover over a 3-6 month period after the initiation of therapy will be
      considered. For example, a decrease of more than 30% in the serum concentration
      of CTX (C-terminal telopeptide of type I collagen) will be regarded as a
      significant change indicating that treatment has reduced bone resorption.

PMID- 19094927
TI  - [Agrecan and articular cartilage: assessment of glycosyltransferases for the
      restoration of cartilage matrix in osteoarthritis].
AB  - Articular cartilage is a connective tissue containing a single type of cells,
      chondrocytes, which synthesise a dense extracellular matrix, mainly composed of
      collagens, hyaluronic acid and proteoglycans. These macromolecules play a major
      role in the resistance and elastic properties of the tissue. They also favour
      interactions with small active substances, such as growth factors and cytokines.
      Chondrocytes have a low metabolic capacity in relatively hypoxic conditions and
      absence of vascular supply. In physiopathological conditions, such as
      osteoarthritis (OA), progressive and irreversible degradation of matrix
      components is occurring. With the aim of developing new and efficient therapies
      against OA, we investigated the molecular mechanisms that initiate the disease,
      in order to identify key-proteins. These targets should hopefully lead to the
      design of new drugs able to stop degradation and restore cartilage. One of the
      earliest molecular events in OA is the degradation of aggrecan, the most abundant
      proteoglycan. The glycosaminoglycan (GAG) chains, chondroitin-sulfate, attached
      on the core protein, are subjected to hydrolysis into smaller fragments. We were
      interested in the glycosyltransferases that catalyse the formation of the
      polysaccharidic chains, namely those involved in the common tetrasaccharidic
      protein linkage region, GlcAbeta1,3Galbeta1,3Galbeta 1,4Xyl-O-Serine. The
      galactose beta1,3-glucuronosyltransferase-I (GlcAT-I) which catalyses the final
      step of this primer and which is markedly repressed during OA is an attractive
      target in that respect. Indeed, the human recombinant enzyme was found to play a
      pivotal role in GAG synthesis. Moreover, overexpression of GlcAT-I in cartilage
      explants treated with IL1beta was able to fully counteract proteoglycan depletion
      induced by the cytokine. These results prompted us to investigate the structure,
      function and regulation of this enzyme. This study provides the basis for several
      therapy approaches (gene delivery, design of glycomimetics able to initiate GAG
      synthesis) to promote cartilage repair.

PMID- 19094928
TI  - [Pathophysiological relevance of peroxisome proliferators activated receptors
      (PPAR) to joint diseases - the pro and con of agonists].
AB  - Peroxisome proliferators activated receptors (PPAR) are ligand-inducible nuclear
      transacting factors comprising three subtypes, PPARalpha, PPARbeta/delta and
      PPARgamma, which play a key role in lipids and glucose homeostasis. All PPAR
      subtypes have been identified in joint or inflammatory cells and their activation
      resulted in a transcriptional repression of pro-inflammatory cytokines (IL-1,
      TNFalpha), early inflammatory genes (NOS(2), COX-2, mPGES-1) or matrix
      metalloproteases (MMP-1, MMP-13), at least for the gamma subtype. PPAR full
      agonists were also shown to stimulate IL-1 receptor antagonist (IL-1Ra)
      production by cytokine-stimulated articular cells in a subtype-dependent manner.
      These anti-inflammatory and anti-catabolic properties were confirmed in animal
      models of joint diseases where PPAR agonists reduced synovial inflammation while
      preventing cartilage destruction or inflammatory bone loss, although many effects
      required much higher doses than needed to restore insulin sensitivity or to lower
      circulating lipid levels. However, these promising effects of PPAR full agonists
      were hampered by their ability to reduce the growth factor-dependent synthesis of
      extracellular matrix components or to induce chondrocyte apoptosis, by the
      possible contribution of immunosuppressive properties to their anti-arthritic
      effects, by the increased adipocyte differentiation secondary to prolonged
      stimulation of PPARgamma, and by a variable contribution of PPAR subtypes
      depending on the system. Clinical data are scarce in rheumatoid arthritis (RA)
      patients whereas thousands of patients worldwilde, treated with PPAR agonists for
      type 2 diabetes or dyslipidemia, are paradoxically prone to suffer from
      osteoarthritis (OA). Whereas high dosage of full agonists may expose RA patients
      to cardiovascular adverse effects, the proof of concept that PPAR agonists have
      therapeutical relevance to OA may benefit from an epidemiological follow-up of
      joint lesions in diabetic or hyperlipidemic patients treated for long periods of
      time with glitazones or fibrates. Additionally, cellular and animal studies are
      required to assess whether partial agonists of PPAR (SPPARMs) may preserve
      therapeutical properties with potentially less safety concern.

PMID- 19094929
TI  - [Cell therapy in cartilage repair: cellular and molecular bases].
AB  - The destruction of articular cartilage represents the outcome of most
      inflammatory and degenerative rheumatic diseases and leads to severe disability.
      Articular cartilage being unable to repair spontaneously, alterations of the
      joint surface often results in end-stage osteoarthritis, requiring surgical
      intervention and total joint replacement. This makes damaged tissues repair a
      major challenge in our aging society. Cartilage harbors only one cell type, the
      chondrocyte, which synthesizes and secretes specific matrix proteins such as type
      II collagen and high molecular weight proteoglycans. Matrix proteins are
      responsible for the conservation of the chondrocyte phenotype and the maintenance
      of the mechanical functions of cartilage. Development of therapeutic strategies
      for cartilage repair should thus comprise not only the replacement of lost
      cartilage cells but also that of extracellular matrix with cartilage-like
      properties. Different protocols are under investigation. The most commonly
      employed materials include transplantation of autologous osteochondral tissue.
      More recently, cell-based therapies using autologous mature chondrocytes or pre
      chondrogenic stem cells have drawn particular attention. Tissue-engineering
      procedures represent the actual trend in cartilage repair. This approach combines
      biodegradable polymeric three-dimensional matrixes and isolated prechondrogenic
      stem cells. The cells are seeded within the biocompatible matrix and then
      implanted into the joint. Numerous non-degradable and degradable polymers, which
      efficiently "mimic" the natural surroundings of cartilage cells, are currently
      under investigation.

PMID- 19094930
TI  - Otitis media: Shifting patterns, practices, priorities--chairman's introduction.

PMID- 19094931
TI  - The rocky road to rational prescribing.
AB  - Primary care physicians frequently see simple cases of acute otitis media (AOM),
      whilst specialists are generally presented with more complicated cases. Despite
      the high disease burden and high rates of consultation, diagnosis and management
      of AOM is currently suboptimal. Furthermore, problems with diagnosis and
      management have a direct impact upon worsening antibiotic resistance. This
      article discusses the unmet needs in AOM that need to be addressed in order to
      improve patient assessment and management. There is a need to further educate the
      public in order to 'demedicalize' this common disease. Effective vaccination is
      also an important component of optimal management.

PMID- 19094932
TI  - Complicated otitis media and its implications.
AB  - Complicated otitis media (OM) is a common paediatric problem and includes two
      major entities: persistent acute OM (AOM) and recurrent AOM (R-AOM). Double
      tympanocentesis studies comparing the microbiology of initial and recurrent
      episodes of AOM have demonstrated that most recurrent episodes occurring within 1
      month after antibiotic therapy are new infections, not true bacteriological
      relapses. These findings have highlighted the importance of bacteriological
      eradication in the prevention of subsequent R-AOM episodes. The seven-valent
      pneumococcal conjugate vaccine (PCV7) targets Streptococcus pneumoniae, one of
      the main AOM pathogens, and data on the impact of PCV7 on complications of AOM,
      such as mastoiditis, are presented.

PMID- 19094933
TI  - The burden of otitis media.
AB  - Otitis media (OM) is one of the most frequent diseases in young children, one of
      the most common reasons for a child to visit a physician, and also the most
      common indication for antibiotic prescribing. OM-related hearing loss due to
      middle ear effusion can delay language acquisition, alter behaviour, and
      influence quality of life. Conclusive evidence is, however, lacking. More insight
      into the individual risk factors is required in order to answer the question of
      why some children recover from OM spontaneously while others need specific
      intervention.

PMID- 19094934
TI  - Otitis media: prospects for prevention.
AB  - Alternatives to vaccination for preventing the considerable morbidity of otitis
      media (OM) are limited. Non-typable Haemophilus influenzae (NTHi) and
      Streptococcus pneumoniae together account for approximately 80% of OM cases
      worldwide, so vaccines against these most serious pathogens should materially
      reduce the burden of OM. Early trial data for a vaccine prototype including NTHi
      and 11 pneumococcal serotypes, interpreted carefully in relation to other trials,
      suggest that OM can now be considered a vaccine-preventable disease. Despite
      differences of scenario according to healthcare and bacteriology circumstances of
      different countries, a provisional analysis of health-economic precedents and
      policy considerations favours vaccination.

PMID- 19094935
TI  - Microbiology of otitis media: a moving target.
AB  - The microbiology of acute otitis media (AOM) is linked to the nasopharyngeal
      commensal flora. This respiratory ecosystem undergoes various selective
      pressures, such as antibiotic consumption and vaccine use. Socio-economic
      conditions also influence the bacterial composition of the nasopharynx.
      Streptococcus pneumoniae, non-encapsulated Haemophilus influenzae, Moraxella
      catarrhalis, and group A Streptococcus are the leading causes of bacterial AOM
      worldwide. This paper will discuss the causes and consequences of recent shifts
      in the underlying microbiology of AOM.

PMID- 19094936
TI  - Rolling back malaria--the next 10 years.

PMID- 19094937
TI  - New era at the NIH.

PMID- 19094938
TI  - Children and psychiatric drugs: disillusion and opportunity.

PMID- 19094939
TI  - Proton-pump inhibitors in peptic ulcer disease.

PMID- 19094940
TI  - National and multinational prospective trial registers.

PMID- 19094941
TI  - Blocking humanitarian assistance: a crime against humanity?

PMID- 19094942
TI  - How doctors feel: affective issues in patients' safety.

PMID- 19094943
TI  - Lunch with The Lancet. Kate Dolan.

PMID- 19094946
TI  - Smokeless tobacco for cigarette cessation?

PMID- 19094948
TI  - Varenicline and smokers with mental illnesses.

PMID- 19094949
TI  - Paan chewing as a risk factor for hepatocellular carcinoma.

PMID- 19094950
TI  - Treatment for Bell's palsy.

PMID- 19094951
TI  - Tobacco tax increase needed in Japan.

PMID- 19094953
TI  - Ankle brachial index vs metabolic syndrome for risk prediction.

PMID- 19094955
TI  - The future is not what it used to be.

PMID- 19094956
TI  - Phenotype, diagnosis, and treatment of Gaucher's disease.
AB  - Gaucher's disease continues to be a model for applications of molecular medicine
      to clinical delineation, diagnosis, and treatment. Analyses of several thousand
      affected individuals have broadened the range of the pan-ethnic disease variants,
      provided initial genotype and phenotype correlations, and established the
      effectiveness of enzyme therapy. Large numbers of affected individuals worldwide
      have provided insight into the effect of disease variation related to ethnic
      origin, prognosis, and outcome. The ability to safely and effectively use enzyme
      therapy to inhibit or reverse visceral-disease progression and involvement has
      provided impetus for design of new enzyme therapies, and creation of substrate
      depletion and pharmacological chaperone strategies. Such innovations could
      provide interventions that are effective for neuronopathic variants and,
      potentially, could be more cost effective than other treatments. These
      developments are novel, clinically important, advancements for patients with
      other lysosomal storage diseases and genetic diseases.

PMID- 19094957
TI  - Cancer and incontinence.

PMID- 19094958
TI  - A cost-effective device for the rapid transfer of gel-separated proteins onto
      membranes.
AB  - We describe here the fabrication of a cost-effective semi-dry blotting apparatus
      for the transfer of proteins onto membranes. Graphite sheets were used as
      electrodes. Protein mixtures were separated on NuPAGE 4% to 12% polyacrylamide
      gradient gels. With a Tris-bicine buffer, we demonstrated that close to 80% of
      the proteins with apparent molecular mass of 80kDa or less were removed from the
      gels after 8min of blotting. The process is much faster than the techniques
      reported previously in the literature.

PMID- 19094959
TI  - mu-Calpain mediated cleavage of the Na+/Ca2+ exchanger in isolated mitochondria
      under A23187 induced Ca2+ stimulation.
AB  - Treatment of bovine pulmonary artery smooth muscle mitochondria with the calcium
      ionophore, A23187 (0.2 microM) stimulates mu-calpain activity and subsequently
      cleaves Na(+)/Ca(2+) exchanger (NCX). Pretreatment of the A23187 treated
      mitochondria with the calpain inhibitors, calpeptin or MDL28170 or with Ca(2+)
      chelator, EGTA does not cleave NCX. Treatment of the mitochondria with A23187
      increases Ca(2+) level in the mitochondria, which subsequently dissociates mu
      calpain-calpastatin association leading to the activation of mu-calpain.
      Immunoblot study of the A23187 treated mitochondria with the NCX polyclonal
      antibody indicates the degradation of mitochondrial inner membrane NCX (110kDa)
      resulting in the doublet of approximately 54-56kDa NCX fragments. Moreover, in
      vitro cleavage of mitochondrial purified NCX by mitochondrial purified mu-calpain
      supports our conclusion. This cleavage of NCX may be interpreted as the main
      cause of Ca(2+) overload and could lay a key role in the activation of apoptotic
      process in pulmonary smooth muscle.

PMID- 19094960
TI  - Key regions of VDAC1 functioning in apoptosis induction and regulation by
      hexokinase.
AB  - The voltage-dependent anion channel (VDAC), located in the mitochondrial outer
      membrane, functions as gatekeeper for the entry and exit of mitochondrial
      metabolites, and thus controls cross-talk between mitochondria and the cytosol.
      VDAC also serves as a site for the docking of cytosolic proteins, such as
      hexokinase, and is recognized as a key protein in mitochondria-mediated
      apoptosis. The role of VDAC in apoptosis has emerged from various studies showing
      its involvement in cytochrome c release and apoptotic cell death as well as its
      interaction with proteins regulating apoptosis, including the mitochondria-bound
      isoforms of hexokinase (HK-I, HK-II). Recently, the functional HK-VDAC
      association has shifted from being considered in a predominantly metabolic light
      to the recognition of its major impact on the regulation of apoptotic
      responsiveness of the cell. Here, we demonstrate that the HK-VDAC1 interaction
      can be disrupted by mutating VDAC1 and by VDAC1-based peptides, consequently
      leading to diminished HK anti-apoptotic activity, suggesting that disruption of
      HK binding to VDAC1 can decrease tumor cell survival. Indeed, understanding
      structure-function relationships of VDAC is critical for deciphering how this
      channel can perform such a variety of differing functions, all important for cell
      life and death. By expressing VDAC1 mutants and VDAC1-based peptides, we have
      identified VDAC1 amino acid residues and domains important for interaction with
      HK and protection against apoptosis. These include negatively- and positively
      charged residues, some of which are located within beta-strands of the protein.
      The N-terminal region of VDAC1 binds HK-I and prevents HK-mediated protection
      against apoptosis induced by STS, while expression of a VDAC N-terminal peptide
      detaches HK-I-GFP from mitochondria. These findings indicate that the interaction
      of HK with VDAC1 involves charged residues in several beta-strands and in the N
      terminal domain. Displacing HK, serving as the 'guardian of the mitochondrion',
      from its binding site on VDAC1 may thus be exploited as an approach to cancer
      therapy.

PMID- 19094961
TI  - HCV infection induces mitochondrial bioenergetic unbalance: causes and effects.
AB  - Cells infected by the hepatitis C virus (HCV) are characterized by endoplasmic
      reticulum stress, deregulation of the calcium homeostasis and unbalance of the
      oxido-reduction state. In this context, mitochondrial dysfunction proved to be
      involved and is thought to contribute to the outcome of the HCV-related disease.
      Here, we propose a temporal sequence of events in the HCV-infected cell whereby
      the primary alteration consists of a release of Ca(2+) from the endoplasmic
      reticulum, followed by uptake into mitochondria. This causes successive
      mitochondrial alterations comprising generation of reactive oxygen and nitrogen
      species and impairment of the oxidative phosphorylation. A progressive adaptive
      response results in an enhancement of the glycolytic metabolism sustained by up
      regulation of the hypoxia inducible factor. Pathogenetic implications of the
      model are discussed.

PMID- 19094962
TI  - Sensory rhodopsin II/transducer complex formation in detergent and in lipid
      bilayers studied with FRET.
AB  - The photophobic receptor from Natronomonas pharaonis (NpSRII) forms a photo
      signalling complex with its cognate transducer (NpHtrII). In order to elucidate
      the complex formation in more detail, we have studied the intermolecular binding
      of both constituents (NpSRII and NpHtrII157; truncated at residue 157) in
      detergent buffers, and in lipid bilayers using FRET. The data for hetero-dimer
      formation of NpSRII/NpHtrII in detergent agrees well with KD values
      (approximately 200 nM) described in the literature. In lipid bilayers, the
      binding affinity between proteins in the NpSRII/NpHtrII complex is at least one
      order of magnitude stronger. In detergent the strength of binding is similar for
      both homo-dimers (NpSRII/NpSRII and NpHtrII/NpHtrII) but significantly weaker (KD
      approximately 16 microM) when compared to the hetero-dimer. The intermolecular
      binding is again considerably stronger in lipid bilayers; however, it is not as
      strong as that observed for the hetero-dimer. At a molar transducer/lipid ratio
      of 1:2000, which is still well above physiological concentrations, only 40% homo
      dimers are formed. Apparently, in cell membranes the formation of the assumed
      functionally active oligomeric 2:2 complex depends on the full-length transducer
      including the helical cytoplasmic part, which is thought to tighten the
      transducer-dimer association.

PMID- 19094963
TI  - Cyclosporin-A potently induces highly cardiogenic progenitors from embryonic stem
      cells.
AB  - Though cardiac progenitor cells should be a suitable material for cardiac
      regeneration, efficient ways to induce cardiac progenitors from embryonic stem
      (ES) cells have not been established. Extending our systematic cardiovascular
      differentiation method of ES cells, here we show efficient and specific expansion
      of cardiomyocytes and highly cardiogenic progenitors from ES cells. An
      immunosuppressant, cyclosporin-A (CSA), showed a novel effect specifically acting
      on mesoderm cells to drastically increase cardiac progenitors as well as
      cardiomyocytes by 10-20 times. Approximately 200 cardiomyocytes could be induced
      from one mouse ES cell using this method. Expanded progenitors successfully
      integrated into scar tissue of infracted heart as cardiomyocytes after cell
      transplantation to rat myocardial infarction model. CSA elicited specific
      induction of cardiac lineage from mesoderm in a novel mesoderm-specific, NFAT
      independent fashion. This simple but efficient differentiation technology would
      be extended to induce pluripotent stem (iPS) cells and broadly contribute to
      cardiac regeneration.

PMID- 19094964
TI  - Inhibition of PI3K by ZSTK474 suppressed tumor growth not via apoptosis but G0/G1
      arrest.
AB  - Phosphoinositide 3-kinase (PI3K) is a potential target in cancer therapy.
      Inhibition of PI3K is believed to induce apoptosis. We recently developed a novel
      PI3K inhibitor ZSTK474 with antitumor efficacy. In this study, we have examined
      the underlying mode of action by which ZSTK474 exerts its antitumor efficacy. In
      vivo, ZSTK474 effectively inhibited the growth of human cancer xenografts. In
      parallel, ZSTK474 treatment suppressed the expression of phospho-Akt, suggesting
      effective PI3K inhibition, and also suppressed the expression of nuclear cyclin
      D1 and Ki67, both of which are hallmarks of proliferation. However, ZSTK474
      treatment did not increase TUNEL-positive apoptotic cells. In vitro, ZSTK474
      induced marked G(0)/G(1) arrest, but did not increase the subdiploid cells or
      activate caspase, both of which are hallmarks of apoptosis. These results clearly
      indicated that inhibition of PI3K by ZSTK474 did not induce apoptosis but rather
      induced strong G(0)/G(1) arrest, which might cause its efficacy in tumor cells.

PMID- 19094965
TI  - Dysbindin engages in c-Jun N-terminal kinase activity and cytoskeletal
      organization.
AB  - A number of reports have provided genetic evidence for an association between the
      DTNBP1 gene (coding dysbindin) and schizophrenia. In addition, sandy mice, which
      harbor a deletion in the DTNBP1 gene and lack dysbindin, display behavioral
      abnormalities suggestive of an association with schizophrenia. However, the
      mechanism by which the loss of dysbindin induces schizophrenia-like behaviors
      remains unclear. Here, we report that small interfering RNA-mediated knockdown of
      dysbindin resulted in the aberrant organization of actin cytoskeleton in SH-SY5Y
      cells. Furthermore, we show that morphological abnormalities of the actin
      cytoskeleton were similarly observed in growth cones of cultured hippocampal
      neurons derived from sandy mice. Moreover, we report a significant correlation
      between dysbindin expression level and the phosphorylation level of c-Jun N
      terminal kinase (JNK), which is implicated in the regulation of cytoskeletal
      organization. These findings suggest that dysbindin plays a key role in
      coordinating JNK signaling and actin cytoskeleton required for neural
      development.

PMID- 19094966
TI  - Angptl 4 deficiency improves lipid metabolism, suppresses foam cell formation and
      protects against atherosclerosis.
AB  - Angiopoietin-like protein family 4 (Angptl 4) has been shown to regulate
      lipoprotein metabolism through the inhibition of lipoprotein lipase (LPL). We
      generated ApoE(-/-)Angptl 4(-/-) mice to study the effect of Angptl 4 deficiency
      on lipid metabolism and atherosclerosis. Fasting and postolive oil-loaded
      triglyceride (TG) levels were largely decreased in ApoE(-/-)Angptl 4(-/-) mice
      compared with and ApoE(-/-)Angptl 4(+/+) mice. There was a significant (75+/-12%)
      reduction in atherosclerotic lesion size in ApoE(-/-)Angptl 4(-/-) mice compared
      with ApoE(-/-) Angptl 4(+/+) mice. Peritoneal macrophages, isolated from Angptl
      4(-/-) mice to investigate the foam cell formation, showed a significant decrease
      in newly synthesized cholesteryl ester (CE) accumulation induced by acetyl low
      density lipoprotein (acLDL) compared with those from Angptl 4(+/+) mice. Thus,
      genetic knockout of Angptl 4 protects ApoE(-/-) mice against development and
      progression of atherosclerosis and strongly suppresses the ability of the
      macrophages to become foam cells in vitro.

PMID- 19094967
TI  - The Kruppel-like factor KLF15 inhibits transcription of the adrenomedullin gene
      in adipocytes.
AB  - KLF15 (Kruppel-like factor 15) plays a key role in adipocyte differentiation and
      glucose transport in adipocytes through activation of its target genes. We have
      now identified six target genes regulated directly by KLF15 in 3T3-L1 mouse
      adipocytes with the use of a combination of microarray-based chromatin
      immunoprecipitation and gene expression analyses. We confirmed the direct
      regulation by KLF15 of one of these genes, that for adrenomedullin, with the use
      of a luciferase reporter assay in 3T3-L1 preadipocytes and adipocytes. Such
      analysis revealed that the most proximal CACCC element in the promoter of the
      human adrenomedullin gene (located in the region spanning nucleotides -70 and 
      29) is required for trans-inhibition by KLF15. Furthermore, chromatin
      immunoprecipitation showed that KLF15 binds to this region of the human
      adrenomedullin gene promoter in cultured human adipocytes. These results thus
      implicate KLF15 in the regulation of adrenomedullin expression in adipose tissue.

PMID- 19094968
TI  - C75 is converted to C75-CoA in the hypothalamus, where it inhibits carnitine
      palmitoyltransferase 1 and decreases food intake and body weight.
AB  - Central nervous system administration of C75 produces hypophagia and weight loss
      in rodents identifying C75 as a potential drug against obesity and type 2
      diabetes. However, the mechanism underlying this effect is unknown. Here we show
      that C75-CoA is generated chemically, in vitro and in vivo from C75 and that it
      is a potent inhibitor of carnitine palmitoyltranferase 1 (CPT1), the rate
      limiting step of fatty-acid oxidation. Three-D docking and kinetic analysis
      support the inhibitory effect of C75-CoA on CPT1. Central nervous system
      administration of C75 in rats led to C75-CoA production, inhibition of CPT1 and
      lower body weight and food intake. Our results suggest that inhibition of CPT1,
      and thus increased availability of fatty acids in the hypothalamus, contribute to
      the pharmacological mechanism of C75 to decrease food intake.

PMID- 19094969
TI  - Psychological investigation of the "feeling of being seen through" in a non
      clinical sample using an ERP paradigm.
AB  - This study aimed to explore the validity of an experiment-based paradigm for
      assessing the suspicious thoughts in healthy volunteers and its corresponding
      neural process. Twenty-four pairs of healthy college students participated in
      this study and were randomly assigned to two experimental conditions: the
      informed (12 pairs) and the naive (12 pairs) conditions. EEG of one subject in
      each pair was recorded when the 'feeling of being seen through' was evoked. The
      findings showed a prominent positive deflection of the difference wave within the
      time window 200 ms-400 ms after stimuli presentation (0 ms) in the naive group.
      The ERP amplitude of frontal and central scalp sites was significantly different
      between high and low paranoia rating scores. These findings provide preliminary
      evidence on the use of an ERP paradigm to detect paranoid ideation or suspicious
      thoughts in non-clinical sample.

PMID- 19094970
TI  - Does the sight of physical threat induce a tactile processing bias? Modality
      specific attentional facilitation induced by viewing threatening pictures.
AB  - Threatening stimuli are thought to bias spatial attention toward the location
      from which the threat is presented. Although this effect is well-established in
      the visual domain, little is known regarding whether tactile attention is
      similarly affected by threatening pictures. We hypothesised that tactile
      attention might be more affected by cues implying physical threat to a person's
      bodily tissues than by cues implying general threat. In the present study,
      participants made temporal order judgments (TOJs) concerning which of a pair of
      tactile (or auditory) stimuli, one presented to either hand, at a range of inter
      stimulus intervals, had been presented first. A picture (showing physical threat,
      general threat, or no threat) was presented in front of one or the other hand
      shortly before the tactile stimuli. The results revealed that tactile attention
      was biased toward the side on which the picture was presented, and that this
      effect was significantly larger for physical threat pictures than for general
      threat or neutral pictures. By contrast, the bias in auditory attention toward
      the side of the picture was significantly larger for general threat pictures than
      for physical threat pictures or neutral pictures. These findings therefore
      demonstrate a modality-specific effect of physically threatening cues on the
      processing of tactile stimuli, and of generally threatening cues on auditory
      information processing. These results demonstrate that the processing of tactile
      information from the body part closest to the threatening stimulus is prioritized
      over tactile information from elsewhere on the body.

PMID- 19094971
TI  - Effects of osmolality on PLP-null myelin structure: implications re axon damage.
AB  - In order to test the adhesiveness of PLP-null compact myelin lamellae we soaked
      aldehyde-fixed CNS specimens from PLP-null and control mice overnight in
      distilled water, in Ringer's solution or in Ringer's solution with added 1 M
      sucrose. Subsequent examination of the tissue by EM showed that both PLP-null and
      control white matter soaked in Ringer remained largely compact. After the
      distilled water soak, control myelin was virtually unchanged, but PLP-null myelin
      showed some decompaction, i.e., separation of myelin lamellae from one another.
      After the sucrose/Ringer soak, normal myelin developed foci of decompaction, but
      the great majority of lamellae remained compact. In the PLP-null specimens, in
      contrast, many of the myelin sheaths became almost completely decompacted. Such
      sheaths became thicker overall and were comprised of lamellae widely separated
      from one another by irregular spaces. Thus, in normal animals, fixed CNS myelin
      lamellae are firmly adherent and resist separation; PLP-null myelin lamellae, in
      contrast, are poorly adherent and more readily separated. Mechanisms by which
      impaired adhesiveness of PLP-null myelin lamellae and fluctuations in osmolality
      in vivo might underlie slowing of conduction and axon damage are discussed.

PMID- 19094972
TI  - Mastication-induced modulation of the jaw-opening reflex during different periods
      of mastication in awake rabbits.
AB  - The present study aimed to determine if sensory inputs from the intraoral
      mechanoreceptors similarly contributed to regulating the activity of the jaw
      opening muscles throughout the masticatory sequence. We also aimed to determine
      if sensory inputs from the chewing and non-chewing sides equally regulated the
      activity of the jaw-opening muscles. Electromyographic (EMG) activities of jaw
      muscles (digastric and masseter) and jaw movements were recorded in awake
      rabbits. The entire masticatory sequence was divided into preparatory, rhythmic
      chewing and preswallow periods, based on jaw muscles activity and jaw movements.
      The jaw-opening reflex (JOR) was evoked by unilateral low-intensity stimulation
      of the inferior alveolar nerve (IAN) on either the chewing or non-chewing side.
      Amplitude of the JOR was assessed by measuring peak-to-peak EMG activity in the
      digastric muscle, and was compared among the masticatory periods and between the
      chewing and non-chewing sides. The JOR was strongly suppressed during the jaw
      closing phase in the rhythmic-chewing and preswallow periods, but this effect was
      transiently attenuated during the late part of the jaw-opening phase in these
      periods. However, modulation of the JOR varied from strong suppression to weak
      facilitation during the preparatory period. The patterns of JOR modulation were
      similar on the chewing and non-chewing sides in all masticatory periods. The
      results suggest that the sensory inputs from the intraoral mechanoreceptors
      regulate the activity of the jaw-opening muscles differently during the
      preparatory period compared with the other masticatory periods. Sensory inputs
      from both the chewing and non-chewing sides similarly regulate the activity of
      the jaw-opening muscles.

PMID- 19094973
TI  - Behavioural disturbances and altered Fos protein expression in adult rats after
      chronic pubertal cannabinoid treatment.
AB  - Cannabis is one of the world's most popular recreational drugs. However, little
      is known about long-lasting cellular and neurobehavioural effects of chronic
      cannabinoid intake, especially during puberty where cannabis use among humans is
      commonly initiated. This study in rats investigates the long-term effect of
      pubertal cannabinoid treatment on prepulse inhibition (PPI), locomotor activity
      and on anxiety in the elevated-plus maze during adulthood. Furthermore, changes
      in adult basic neuronal activity, assessed by c-Fos immunoreactivity (Fos IR),
      and a potentially altered Fos expression after acute treatment with dopaminergic
      drugs was evaluated. Chronic treatment with the synthetic cannabinoid full
      agonist WIN 55,212-2 (WIN; 1.2 mg/kg) was carried out over 25 days of the rats'
      puberty and subsequent behavioural testing was conducted in adult animals.
      Finally, Fos IR was evaluated in several brain regions under basal conditions and
      after acute administration of haloperidol (0.1 mg/kg) and apomorphine (2 mg/kg).
      Chronic WIN treated animals exhibited a lasting disruption of PPI. These rats
      were also more active in the open field and less anxious in the elevated-plus
      maze than their vehicle treated controls. Additionally, when comparing Fos IR in
      selected brain regions, these animals displayed altered basal neuronal activity
      and responded differently to acute application of haloperidol or apomorphine.
      Taken together, these results indicate that chronic stimulation of the
      cannabinoid receptor CB(1) during the rats' puberty not only leads to persistent
      behavioural changes but also to cellular long-term adaptations within brain
      regions critical for drug of abuse or neuropsychiatric diseases.

PMID- 19094974
TI  - Liposomes containing alkylated methotrexate analogues for phospholipase A(2)
      mediated tumor targeted drug delivery.
AB  - Two lipophilic methotrexate analogues have been synthesized and evaluated for
      cytotoxicity against KATO III and HT-29 human colon cancer cells. Both analogues
      contained a C16-alkyl chain attached to the gamma-carboxylic acid and one of the
      analogues had an additional benzyl group attached to the alpha-carboxylic acid.
      The cytotoxicity of the gamma-alkylated compound towards KATO III (IC(50) = 55
      nM) and HT-29 (IC(50) = 400 nM) cell lines, was unaffected by the alkylation,
      whereas the additional benzyl group on the alpha-carboxyl group made the compound
      nontoxic. The gamma-derivative with promising cytotoxicity was incorporated into
      liposomes that were designed to be particularly susceptible to a liposome
      degrading enzyme, secretory phospholipase A(2) (sPLA(2)), which is found in high
      concentrations in tumors of several different cancer types. Liposome
      incorporation was investigated by differential scanning calorimetry (DSC), and
      sPLA(2) hydrolysis was examined by fluorescence spectroscopy and high performance
      liquid chromatography (HPLC). The results showed that the methotrexate (MTX)
      analogue could be incorporated into liposomes that were degradable by sPLA(2).
      However, the in vitro cytotoxicity of the MTX-liposomes against KATO III and HT
      29 cancer cells was found to be independent of sPLA(2) hydrolysis, indicating
      that the alkylated MTX-analogue was available for cancer cell uptake even in the
      absence of liposome hydrolysis. Using a DSC based method for assessing the
      anchoring stability of alkylated compounds in liposomes, it was demonstrated that
      the MTX-analogue partitioned into the water phase and thereby became available
      for cell uptake. It was concluded that liposomes containing alkylated MTX
      analogues show promise as a drug delivery system, although the MTX-analogue needs
      to be more tightly anchored to the liposomal carrier. Also, the developed DSC
      assay for studying the anchoring stability of alkylated drugs will be a useful
      tool in the development of liposomal drug delivery systems.

PMID- 19094975
TI  - With a novel evaluation method comparison of 2 homogeneous assay kits for high
      density lipoprotein cholesterol.
AB  - BACKGROUND: 2 homogeneous assay kits, Determiner L HDL-C from Kyowa Medex, Co.,
      Ltd. (Tokyo, Japan) (KWM) and Cholestest NHDL from Daiichi Pure Chemical, Co.,
      Ltd. (Tokyo, Japan) (DIC), for HDL-C are widely used in laboratory tests
      worldwide. Meanwhile, it was reported that free cholesterol (FC) in HDL is not
      measured with one of these kits. We devised a novel evaluation method and
      analyzed the 2 kits in detail. METHODS: Using HPLC, the residual amounts of
      cholesterol in reaction mixtures were compared before and after reaction with
      homogeneous reagents. Healthy sera were reacted with homogeneous reagents or with
      heated, non-enzyme reagents from each kit. The FC and total cholesterol in each
      lipoprotein were continuously measured with HPLC. RESULTS: With KWM, the HDL-C
      was measured >95%.With DIC, all FC in sera was eliminated in the first reaction,
      and FC in HDL was not measured. Moreover, the peak X that was assumed to be a
      part of HDL was separated with DIC, and the cholesterol in the peak X was not
      measured. CONCLUSIONS: 2 HDL-C assay kits were compared using a novel evaluation
      method. KWM was good overall. DIC was found to have 2 problems: 1) FC in HDL was
      not measured, and 2) the cholesterol in peak X that was assumed to be a part of
      HDL was not measured.

PMID- 19094976
TI  - Identifying novel autoantibody signatures in ovarian cancer using high-density
      protein microarrays.
AB  - OBJECTIVES: To identify autoantibody signatures in ovarian cancer using protein
      microarray technology. DESIGN AND METHODS: Protein microarrays were screened
      using non-malignant peritoneal fluid (n=30) and ascites fluid pooled from ovarian
      cancer patients (n=30). RESULTS: Fifteen potential tumour-associated antigens
      were discovered. AASDHPPT showed the strongest signal-to-noise ratio.
      CONCLUSIONS: Protein microarrays are suitable for autoantibody discovery in
      ovarian cancer but the signatures are of low frequency.

PMID- 19094977
TI  - Sperm head defects and disturbances in spermatozoal chromatin and DNA integrities
      in idiopathic infertile subjects: association with cigarette smoking.
AB  - OBJECTIVES: To evaluate sperm chromatin and DNA integrities in idiopathic
      infertile men and determine the possible association(s) of cigarette smoking on
      oxidative stress markers, antioxidant capacity and semen quality. SUBJECTS AND
      METHODS: Semen samples from men referring to the andrology laboratory were
      categorized into 3 groups: fertile non-smokers (n=16), infertile non-smokers
      (n=36), and infertile smokers (n=34). Semen analysis was performed according to
      WHO criteria. The percentage of sperm DNA fragmentation index (%DFI) and the
      percentage of sperm with abnormally high DNA stainability (HDS%; immature
      spermatozoa) were determined by SCSA using the metachromatic properties of
      acridine orange. Lipid peroxidation, superoxide dismutase (SOD), catalase (CAT)
      and reduced glutathione (GSH) levels in seminal plasma and spermatozoa were
      measured by spectrophotometric assays. RESULTS: The classical semen parameters
      were negatively correlated with lipid peroxidation in spermatozoa; motility and
      morphology were negatively correlated with %DFI (p<0.05). HDS% was also
      negatively correlated with above markers except for morphology (r=-0.352,
      p=0.081). DFI% and HDS% were significantly higher in the infertile smokers group
      than in infertile non-smokers (p=0.032; p=0.001 respectively). Cigarette smoking
      was significantly associated with DFI%, HDS%, TBARS and the fraction of "round
      headed" sperm (r=0.796, p=0.0001; r=0.371, p=0.033; r=0.606, r=0.591, p=0.001
      respectively), and decreased SOD levels (r=-0.545). CONCLUSION: DFI%, HDS% and
      round-head sperms are increased in idiopathic infertile men; this increase is
      associated with cigarette smoking. These defects may be attributed to increased
      oxidative stress and insufficient scavenging antioxidant enzymes in the seminal
      fluid of infertile patients.

PMID- 19094978
TI  - Coenzyme Q10 deficiency associated with a mitochondrial DNA depletion syndrome: a
      case report.
AB  - OBJECTIVES: To report on a case with a mitochondrial DNA (mtDNA) depletion
      syndrome. DESIGN AND METHODS: Laboratory studies were done in muscle biopsy and
      fibroblasts to evaluate coenzyme Q(10) (CoQ(10)) status and quantify
      mitochondrial DNA. RESULTS: Decreased CoQ(10) values and a 78% of mtDNA depletion
      were detected in muscle. Mutational studies failed to reveal any pathogenic
      mutation in nuclear genes related with mtDNA maintenance. CONCLUSIONS: mtDNA
      depletion syndrome was associated with CoQ(10) deficiency in our patient.

PMID- 19094979
TI  - A comparative study of freezing single cells and spheroids: towards a new model
      system for optimizing freezing protocols for cryobanking of human tumours.
AB  - Cryopreservation of human tumour cells and tissue is a valuable tool for
      retrospective analysis and for the transport and handling of biopsy material.
      Tumour tissue consists of different cell types, which have different optimal
      freezing conditions, and extracellular matrix. A well-defined and authentic model
      system is required for developing new freezing protocols and media. This work
      describes the use of L929 and PC-3 spheroids as new model systems for freezing
      human tumours. Cell suspension and spheroids were frozen in different vessels (1
      ml cryovials and a special, cryo-compatible 30 x 25 microl multi well plate) at
      slow rate (1 degrees C/min). Freezing media were combinations of culture or
      tumour transport medium (Liforlab) with the cryoprotective agents, Me(2)SO,
      trehalose and modified starch. We also present a new method of evaluating the
      viability of three dimensional multicellular systems to compare thawed spheroids
      objectively. Best viability (70%) of L929 spheroids occurred with a combination
      of Liforlab and starch hydrolysis product. The best cryopreservation results for
      spheroids were found with extracellular cryoprotectants, while optimum viability
      of single cells was achieved with Me(2)SO.

PMID- 19094980
TI  - A specific transcriptional response of yeast cells to camptothecin dependent on
      the Swi4 and Mbp1 factors.
AB  - Topoisomerase I (Top1) is the specific target of the anticancer drug camptothecin
      (CPT) that interferes with enzyme activity promoting Top1-mediated DNA breaks and
      inhibition of DNA and RNA synthesis. To define the specific transcriptional
      response to CPT, we have determined the CPT-altered transcription profiles in
      yeast by using a relatively low concentration of the drug. CPT could alter global
      expression profiles only if a catalytically active Top1p was expressed in the
      cell, demonstrating that drug interference with Top1 was the sole trigger of the
      response. A total of 95 genes showed a statistically-significant alterations.
      Gene Ontology term analyses suggested that the cell response was mainly to the
      inhibition of nucleic acid synthesis and cell cycle progression. Promoter
      sequence analyses of the 22 up-regulated genes and expression studies in gene
      deleted strains showed that the transcription factors, Swi4p and Mbp1p, mediate
      at least partially the transcriptional response to CPT. The MBP1 gene deletion
      abrogates a transient cell growth delay caused by CPT whereas the SWI4 gene
      deletion increases yeast resistance to CPT. Thus, the findings show that yeast
      cells have a highly selective and sensitive transcriptional response to CPT
      depending on SWI4 and MBP1 genes suggesting a complex regulation of cell cycle
      progression by the two factors in the presence of CPT.

PMID- 19094981
TI  - Molecular discrimination of multiple primary versus metastatic squamous cell
      cancers of the head/neck and lung.
AB  - Patients with squamous cell carcinoma (SqCa) arising in the head and neck (H/N)
      commonly develop solitary pulmonary metastases that mimic the clinical,
      radiographic, and pathologic presentation of new primary lung SqCa. Primary
      pulmonary and metastatic SqCas cannot be differentiated from each other
      histologically. However, distinguishing multiple independent primary neoplasms
      from a primary H/N SqCa with pulmonary metastasis has prognostic significance due
      to its impact on tumor stage, the most important determinant of prognosis. Since
      genomic instability is a common feature of cancer, we hypothesized that
      independently-arising neoplasms in an individual patient would exhibit measurable
      genomic variation, enabling discrimination of tumor lineage and relatedness. In
      this study, we describe a molecular approach for analysis of genetic variation
      among multiple tumors from a single patient that does not rely on collection of
      normal tissue, and which can be performed with minimal tumor samples. Genomic DNA
      from H/N and lung SqCas from individual patients were analyzed by microsatellite
      PCR to identify discordant allelic variation. This method is rapid, sensitive,
      does not require constitutional DNA for comparison, and can be applied to the
      analysis of archival tumor DNA. Our results demonstrate that microsatellite PCR
      can identify discordant genetic variation among multiple tumors from a single
      patient, facilitating the molecular discrimination of metachronous primary SqCa
      versus solitary pulmonary metastasis from a H/N primary SqCa.

PMID- 19094982
TI  - Expression and tissue localization of beta-catenin, alpha-actinin and chondroitin
      sulfate proteoglycan 6 is modulated during rat and human left ventricular
      hypertrophy.
AB  - Left ventricular hypertrophy (LVH) correlates with chronic renal failure and is
      one of the most important causes of cardiac mortality. The understanding of the
      molecular complexity of the disease will help to find biomarkers that open new
      perspectives about early diagnosis and therapy. This work describes the
      identification of mediators during pathogenesis relevant for structural
      remodeling processes of cardiac tissue in uremic LVH. An established rat model of
      chronic renal failure allowed whole-genome transcriptome analyses as well as the
      investigation of differential expressed proteins in uremic LVH. The localization
      of potential biomarkers encoded by candidate genes was done by
      immunohistochemical analyses of cardiac tissue of the animal model as well as
      cardiac sections of LVH diseased patients. In addition, the induction of human
      cardiac fibroblasts (HCF) and human umbilical vein endothelial cells (HUVEC) with
      the LVH mediator angiotensin II enabled us to investigate uremic LVH progression
      in vitro. These results point to alterations of myocardial intercellular and cell
      matrix contacts in hypertrophic cardiac tissue. Obviously, structural changes of
      the extracellular matrix are significantly modulated by beta-catenin associated
      signaling pathways. Interestingly, intracellular translocation of beta-catenin,
      alpha-actinin and chondroitin sulfate proteoglycan 6 (CSPG6/SMC3) was observed in
      the animal model and in LVH patients. Our results show that the parallel
      investigation of rat and human cardiac tissue as well as human cellular models in
      vitro represents a promising strategy to identify reliable biomarkers of LVH.

PMID- 19094983
TI  - Cytoplasmic expression and specific binding of the VH/VL single domain
      intrabodies in transfected NIH3T3 cells.
AB  - Intracellularly expressed antibody fragments (intrabodies) have been utilized as
      powerful tools not only for clinical applications but also for the functional
      analysis of proteins inside the cell. Among several types of intrabodies
      developed so far, single domain types composed of only the variable regions (V(H)
      or V(L)) of antibodies are the smallest and thus the easiest to design. In this
      study, four types of single domain intrabodies were evaluated against a cytosolic
      protein, Wiskott-Aldrich syndrome protein (WASP), in gene-transfected NIH3T3
      cells. These single domains were composed of the V(H) and V(L) region with or
      without their leader sequences. Although these single domains were expressed at
      similar levels in NIH3T3 cells, the binding activity to the cytosolic target was
      higher in the single domain constructs with leader sequences. These results
      suggest the usefulness of the single domain intrabody constructs to analyze the
      functional domains of cytosolic proteins in cells.

PMID- 19094984
TI  - Netrin-4 regulates angiogenic responses and tumor cell growth.
AB  - Netrin-4 is a 628 amino acid basement membrane component that promotes neurite
      elongation at low concentrations but inhibits neurite extension at high
      concentrations. There is a growing body of literature suggesting that several
      molecules, including netrins, are regulators of both neuronal and vascular
      growth. It is believed that molecules that guide neural growth and development
      are also involved in regulating morphogenesis of the vascular tree. Further,
      netrins have recently been implicated in controlling epithelial cell branching
      morphogenesis in the breast, lung and pancreas. Characterization of purified
      netrin-4 in in vitro angiogenesis assays demonstrated that netrin-4 markedly
      inhibits HMVEC migration and tube formation. Moreover, netrin-4 inhibits
      proliferation of a variety of human tumor cells in vitro. Netrin-4 has only
      modest effects on proliferation of endothelial and other non-transformed cells.
      Netrin-4 treatment results in phosphorylation changes of proteins that are known
      to control cell growth. Specifically, Phospho-Akt-1, Phospho-Jnk-2, and Phospho-c
      Jun are reduced in tumor cells that have been treated with netrin-4. Together,
      these data suggest a potential role for netrin-4 in regulating tumor growth.

PMID- 19094985
TI  - All-trans retinoic acid remodels extracellular matrix and suppresses laminin
      enhanced contractility of cultured human retinal pigment epithelial cells.
AB  - All-trans retinoic acid (atRA) has been reported to inhibit the proliferation of
      retinal pigment epithelial (RPE) cells and used in treatment of proliferative
      vitreoretinopathy (PVR) in animal model. This study aimed at examining the
      effectiveness of atRA in inhibiting the extracellular matrix (ECM) biosynthesis
      by RPE cells and the RPE cell-mediated collagen gel contraction. Cultured RPE
      cells were treated with atRA and the expression of four ECM proteins (collagen
      types I, III, IV and laminin beta1) was profiled. The results indicated that atRA
      treatment up-regulated de novo synthesis of collagen type I, but decreased that
      of laminin beta1 in a dose-dependent manner. Moreover, the effect of atRA on RPE
      cell contraction was evaluated by measuring the area of collagen gel where RPE
      cells populated. Treatment with atRA significantly inhibited RPE cell-mediated
      collagen gel contraction. Addition of exogenous laminin nonapeptide into gels
      promoted RPE cell contraction, while atRA reversed the laminin-enhanced
      contractility. atRA treatment significantly suppressed the gene expression of
      integrin beta3 but not alphaV subunit, and effectively inhibited the tyrosine
      phosphorylation of integrin beta3 at residue 747 in RPE cells grown on laminin
      coated dish, suggesting that atRA may suppress the RPE contractility through
      either inhibiting integrin beta3 expression or abrogating the integrin beta3
      mediated signaling. In conclusion, atRA pharmacologically possesses a tissue
      remodeling capacity and inhibits contractility of RPE cells. Therefore, atRA
      might be potentially a therapeutic agent for certain ocular disorders such as
      PVR.

PMID- 19094987
TI  - Vitex negundo attenuates calpain activation and cataractogenesis in selenite
      models.
AB  - Recent investigations have shown that phytochemical antioxidants can scavenge
      free radicals and prevent various diseases. Cataract is the leading cause of
      blindness and is associated with oxidative damage of the lens. Selenite-induced
      cataract in rat pups is an excellent mimic of oxidative stress-induced cataract.
      Selenite cataract is associated with oxidative stress, loss of calcium
      homeostasis, calpain activation and protein insolubilization in the lens. Our
      present study focuses on the isolation of flavonoids from Vitex negundo and to
      assess its efficacy in preventing these changes in the lens of selenite-induced
      cataract models. Eight-day-old Sprague-Dawley rat pups were used for the study
      and divided into four groups: Control (G I), Sodium selenite-induced (G II),
      Sodium selenite+quercetin treated (G III), Sodium selenite+flavonoids from Vitex
      negundo (FVN) (G IV). Cataract was induced by a single subcutaneous injection of
      Sodium selenite (4 mg/Kg body weight) on the 10th day. Treatment groups received
      quercetin (1.0mg/Kg body weight) and FVN (1.0mg/Kg body weight) intraperitoneally
      from 8th to 15th day. Cataract was visualized from the 16th day. Morphological
      examination of the rat lenses revealed no opacification in G I and mild
      opacification in G III and G IV (stage 1) whereas dense opacification in G II
      (stage 4-6). The activities of superoxide dismutase (SOD), catalase,
      Ca(2+)ATPase, concentration of reduced glutathione (GSH) and protein sulfhydryl
      content were significantly increased in G III and G IV compared to G II, while
      decreased activities of calpains, lower concentration of calcium and
      thiobarbituric acid reactive substances (TBARS) were observed in G III and IV as
      compared to G II. Lens protein profile of water soluble proteins showed normal
      levels of expression in treated groups compared to that of selenite-induced rats.
      These results indicate good antioxidant and therapeutic potential of FVN in
      modulating biochemical parameters against selenite-induced cataract, which have
      been reported in this paper for the first time.

PMID- 19094986
TI  - Development of lead hammerhead ribozyme candidates against human rod opsin mRNA
      for retinal degeneration therapy.
AB  - To identify lead candidate allele-independent hammerhead ribozymes (hhRz) for the
      treatment of autosomal dominant mutations in the human rod opsin (RHO) gene, we
      tested a series of hhRzs for potential to significantly knockdown human RHO gene
      expression in a human cell expression system. Multiple computational criteria
      were used to select target mRNA regions likely to be single stranded and
      accessible to hhRz annealing and cleavage. Target regions are tested for
      accessibility in a human cell culture expression system where the hhRz RNA and
      target mRNA and protein are coexpressed. The hhRz RNA is embedded in an
      adenoviral VAI RNA chimeric RNA of established structure and properties which are
      critical to the experimental paradigm. The chimeric hhRz-VAI RNA is abundantly
      transcribed so that the hhRzs are expected to be in great excess over substrate
      mRNA. HhRz-VAI traffics predominantly to the cytoplasm to colocalize with the RHO
      mRNA target. Colocalization is essential for second-order annealing reactions.
      The VAI chimera protects the hhRz RNA from degradation and provides for a long
      half-life. With cell lines chosen for high transfection efficiency and a molar
      excess of hhRz plasmid over target plasmid, the conditions of this experimental
      paradigm are specifically designed to evaluate for regions of accessibility of
      the target mRNA in cellulo. Western analysis was used to measure the impact of
      hhRz expression on RHO protein expression. Three lead candidate hhRz designs were
      identified that significantly knockdown target protein expression relative to
      control (p<0.05). Successful lead candidates (hhRz CUC [see in text downward
      arrow] 266, hhRz CUC [see in text downward arrow] 1411, hhRz AUA [see in text
      downward arrow] 1414) targeted regions of human RHO mRNA that were predicted to
      be accessible by a bioinformatics approach, whereas regions predicted to be
      inaccessible supported no knockdown. The maximum opsin protein level knockdown is
      approximately 30% over a 48h paradigm of testing. These results validate a
      rigorous computational bioinformatics approach to detect accessible regions of
      target mRNAs in cellulo. The opsin knockdown effect could prove to be clinically
      significant when integrated over longer periods in photoreceptors. Further
      optimization and animal testing are the next step in this stratified RNA drug
      discovery program. A recently developed novel and efficient screening assay based
      upon expression of a dicistronic mRNA (RHO-IRES-SEAP) containing both RHO and
      reporter (SEAP) cDNAs was used to compare the hhRz 266 lead candidate to another
      agent (Rz525/hhRz485) already known to partially rescue retinal degeneration in a
      rodent model. Lead hhRz 266 CUC [see in text downward arrow] proved more
      efficacious than Rz525/hhRz485 which infers viability for rescue of retinal
      degeneration in appropriate preclinical models of disease.

PMID- 19094988
TI  - Enhanced pronociception by amygdaloid group I metabotropic glutamate receptors in
      nerve-injured animals.
AB  - Peripheral neuropathy has been associated with structural and functional changes
      of the amygdala, a key player in emotions. Here we study whether peripheral
      neuropathy influences pain regulation by the amygdala. For this purpose, we
      determined discharge rates of presumably pro- and antinociceptive pain-regulatory
      neurons in the rostral ventromedial medulla (RVM) following microinjection of
      various glutamatergic compounds into the central nucleus of the amygdala. RVM
      neurons were recorded in pentobarbitone-anesthetized rats with a peripheral nerve
      injury or sham-operation. In a separate behavioral experiment, we determined
      whether the influence of amygdaloid administration of a glutamatergic compound on
      affective pain-related behavior, as assessed by an aversive place-conditioning
      test, is changed by neuropathy. While glutamate or an NMDA receptor antagonist in
      the amygdala failed to induce marked changes in discharge rates of RVM cells,
      amygdaloid administration of DHPG, a group I metabotropic glutamate receptor
      (mGluR) agonist acting on mGluR(1) and mGluR(5), increased discharge rates of
      presumably pronociceptive RVM ON-cells in nerve-injured but not sham-operated
      animals. This pronociceptive effect of DHPG was reversed by MPEP (mGluR(5)
      antagonist) and CPCCOEt (mGluR(1) antagonist). CHPG, an mGluR(5) agonist, failed
      to influence ON-cell activity and DHPG failed to influence activity of presumably
      antinociceptive RVM OFF-cells. Amygdaloid administration of DHPG increased and
      that of CPCCOEt decreased affective pain-related behavior in nerve-injured
      animals. The results suggest that following nerve injury, the amygdaloid group I
      mGluR, particularly subtype mGluR(1), has an enhanced pronociceptive effect
      providing a potential mechanism for emotional enhancement of pain in peripheral
      neuropathy.

PMID- 19094989
TI  - Therapeutic benefits of angiogenetic gene-modified human mesenchymal stem cells
      after cerebral ischemia.
AB  - Intravenous transplantation of human mesenchymal stem cells (hMSCs) expanded from
      adult bone marrow ameliorates functional deficits in rat cerebral infarction
      models. Several hypotheses to account for the therapeutic mechanisms have been
      suggested, but angiogenesis is thought to be of critical importance. Recently, we
      have reported the therapeutic benefits of hMSCs which have been transfected with
      the angiopoietin-1 gene in a rat permanent middle cerebral artery occlusion
      (MCAO) model. To potentially enhance the therapeutic effects of angiopoietin-1
      gene-modified hMSC (Ang-hMSC), we transfected hMSCs with the angiopoietin-1 gene
      and the VEGF gene, and investigated whether the combination of Ang-1 and VEGF
      gene-modified hMSCs (Ang-VEGF-hMSC) contribute to functional recovery in a rat
      MCAO model. We induced MCAO using intraluminal vascular occlusion, and hMSCs, Ang
      hMSCs, VEGF-hMSCs or Ang-VEGF-hMSCs were intravenously infused 6 h later. MRI and
      behavioral analyses revealed that rats receiving Ang-VEGF-hMSCs showed the
      greatest structural-functional recovery as compared to the other groups. These
      results suggest that intravenous administration of hMSCs transfected with the
      angiopoietin-1 and VEGF gene using a fiber-mutant adenovirus vector may represent
      a new strategy for the treatment of ischemia.

PMID- 19094990
TI  - Schistosoma mansoni: developmental arrest of miracidia treated with histone
      deacetylase inhibitors.
AB  - In the present study, we examined the effect of the histone deacetylase (HDAC)
      inhibitors trichostatin A (TSA), valproic acid (VA) and sodium-butyrate on the
      metamorphosis of larvae of the human blood-fluke Schistosoma mansoni from the
      free-swimming miracidia into the intramolluskal sporocyst. We show that HDAC
      inhibitors block transformation in concentration dependant manner. TSA reversibly
      blocks this developmental process: only 13+/-11% of TSA treated miracidia
      transform into sporocysts in-vitro, compared to 92+/-3% in the mock-treated
      control. Other enzyme inhibitors such as cycloheximide or hydroxyurea had no
      effect on metamorphosis. For treatment of up to 4 h, the effect of TSA was
      completely reversible. Our data indicates that HDAC activity is necessary for the
      transformation of S. mansoni miracidia during infection of the snail host.

PMID- 19094991
TI  - Increased expression and intramitochondrial translocation of cyclophilin-D
      associates with increased vulnerability of the permeability transition pore to
      stress-induced opening during compensated ventricular hypertrophy.
AB  - Opening of the permeability transition pore (PTP) of mitochondria is a critical
      permeation event that compromises cell viability and may constitute a factor that
      participates to the loss of cardiomyocytes in compromised hearts. Mitochondria
      from hearts with volume overload-induced compensated hypertrophy are more
      vulnerable to opening of the PTP opening in response to a Ca2+ stress. Several of
      the factors known to affect PTP opening, including respiratory function, membrane
      potential, the rate of mitochondrial Ca2+ uptake and endogenous levels of Ca2+ in
      the mitochondrial matrix, were not altered by volume overload. In contrast, there
      was an 80% increase in the abundance of the PTP regulating protein cyclophilin-D
      and a 3.7 fold enhancement of Cyp-D binding to membrane, which all predispose to
      PTP opening. Mitochondria from volume overloaded animals also displayed elevated
      rates of production of reactive oxygen species, which may be causally related to
      both the intramitochondrial translocation of cyclophilin-D and PTP opening, since
      incubation of cardiac mitochondria with terbutylhydroperoxyde in vitro increased
      to binding of cyclophilin-D to mitochondrial membranes in a dose-related fashion,
      except when cyclosporin A (a ligand of cyclophilin D with a known ability to
      delay PTP opening) was present prior to the addition of terbutylhydroperoxyde.
      Taken together, these results constitute the first evidence obtained in a
      pathophysiologic situation that increased abundance of cyclophilin-D within
      mitochondrial membranes may increase mitochondrial vulnerability to stress, and
      thus possibly initiate a vicious cycle of cellular dysfunction that may
      ultimately lead to activation of cell death.

PMID- 19094992
TI  - The SV40 capsid is stabilized by a conserved pentapeptide hinge of the major
      capsid protein VP1.
AB  - The simian virus 40 (SV40) outer shell is composed of 72 pentamers of VP1. The
      core of the VP1 monomer is a beta-barrel with jelly-roll topology and extending N
      and C-terminal arms. A pentapeptide hinge, KNPYP, tethers the C-arm to the VP1
      beta-barrel core. The five C-arms that extend from each pentamer insert into the
      neighbouring pentamers, tying them together through different types of
      interactions. In the mature virion, this element adopts either of six
      conformations according to their location in the capsid. We found that the hinge
      is conserved among 16 members of the Polyomaviridae, attesting to its importance
      in capsid assembly and/or structure. We have used site-directed mutagenesis to
      gain an understanding into the structural requirements of this element: Y299 was
      changed to A, F, and T, and P300 to A and G. The mutants showed reduction in
      viability to varying degrees. Unexpectedly, assembly was reduced only to a small
      extent. However, the data showed that the mutants were highly unstable. The
      largest effect was observed for mutations of P300, indicating a role of the
      proline in the virion structure. P300G was more unstable than P300A, indicating a
      requirement for rigidity of the pentapeptide hinge. Y299T and Y299A were more
      defective in viability than Y299F, highlighting the importance of an aromatic
      ring at this position. Structural inspection showed that this aromatic ring
      contacts C-arms of neighbouring pentamers. Computational modelling predicted loss
      of stability of the Y mutants in concordance with the experimental results. This
      study provides insights into the structural details of the pentapeptide hinge
      that are responsible for capsid stability.

PMID- 19094993
TI  - Crystal structure of the parasporin-2 Bacillus thuringiensis toxin that
      recognizes cancer cells.
AB  - Parasporin-2 is a protein toxin that is isolated from parasporal inclusions of
      the Gram-positive bacterium Bacillus thuringiensis. Although B. thuringiensis is
      generally known as a valuable source of insecticidal toxins, parasporin-2 is not
      insecticidal, but has a strong cytocidal activity in liver and colon cancer
      cells. The 37-kDa inactive nascent protein is proteolytically cleaved to the 30
      kDa active form that loses both the N-terminal and the C-terminal segments.
      Accumulated cytological and biochemical observations on parasporin-2 imply that
      the protein is a pore-forming toxin. To confirm the hypothesis, we have
      determined the crystal structure of its active form at a resolution of 2.38 A.
      The protein is unusually elongated and mainly comprises long beta-strands aligned
      with its long axis. It is similar to aerolysin-type beta-pore-forming toxins,
      which strongly reinforce the pore-forming hypothesis. The molecule can be divided
      into three domains. Domain 1, comprising a small beta-sheet sandwiched by short
      alpha-helices, is probably the target-binding module. Two other domains are both
      beta-sandwiches and thought to be involved in oligomerization and pore formation.
      Domain 2 has a putative channel-forming beta-hairpin characteristic of aerolysin
      type toxins. The surface of the protein has an extensive track of exposed side
      chains of serine and threonine residues. The track might orient the molecule on
      the cell membrane when domain 1 binds to the target until oligomerization and
      pore formation are initiated. The beta-hairpin has such a tight structure that it
      seems unlikely to reform as postulated in a recent model of pore formation
      developed for aerolysin-type toxins. A safety lock model is proposed as an
      inactivation mechanism by the N-terminal inhibitory segment.

PMID- 19094996
TI  - Avian flu pandemic: Can we prevent it?
AB  - Outbreaks of highly pathogenic H5N1 avian influenza in Southeast Asia, Europe and
      Africa have led to devastating consequences for poultry, and have resulted in
      numerous infections in humans. Although these infections from the animal
      reservoir continue to accumulate, the virus does not seem to spread extensively
      among humans. However, for example, a process of genetic reassortment could occur
      in a human who is co-infected with avian influenza A virus and a human strain of
      influenza A virus. The resulting new virus might then be able to easily infect
      humans and spread from human to human. Therefore, many experts expect the
      occurrence of a pandemic due to a mutant virus which can be easily transmitted
      among humans. Thus, currently, a major public health concern is the next
      influenza pandemic; yet it remains unclear how to control such a crisis. In this
      paper, we investigate relations between the evolution of virulence and an
      effectiveness of pandemic control measures after the emergence of mutant avian
      influenza; one is an elimination policy of infected birds with avian influenza
      and the other is a quarantine policy of infected humans with mutant avian
      influenza. We found that each of these prevention policies can be ineffective
      (i.e., increase human morbidity or mortality). Further, interestingly, the same
      intervention might, under the same conditions, increase human morbidity and
      decrease human mortality, or vice versa. Our practical findings are that the
      quarantine policy can effectively reduce both human morbidity and mortality but
      the elimination policy increases either human morbidity or mortality in a worst
      case situation.

PMID- 19094994
TI  - How do type II topoisomerases use ATP hydrolysis to simplify DNA topology beyond
      equilibrium? Investigating the relaxation reaction of nonsupercoiling type II
      topoisomerases.
AB  - DNA topoisomerases control the topology of DNA (e.g., the level of supercoiling)
      in all cells. Type IIA topoisomerases are ATP-dependent enzymes that have been
      shown to simplify the topology of their DNA substrates to a level beyond that
      expected at equilibrium (i.e., more relaxed than the product of relaxation by ATP
      independent enzymes, such as type I topoisomerases, or a lower-than-equilibrium
      level of catenation). The mechanism of this effect is currently unknown, although
      several models have been suggested. We have analyzed the DNA relaxation reactions
      of type II topoisomerases to further explore this phenomenon. We find that all
      type IIA topoisomerases tested exhibit the effect to a similar degree and that it
      is not dependent on the supercoil-sensing C-terminal domains of the enzymes. As
      recently reported, the type IIB topoisomerase, topoisomerase VI (which is only
      distantly related to type IIA enzymes), does not exhibit topology simplification.
      We find that topology simplification is not significantly dependent on circle
      size in the range approximately 2-9 kbp and is not altered by reducing the free
      energy available from ATP hydrolysis by varying the ADP:ATP ratio. A direct test
      of one model (DNA tracking; i.e., sliding of a protein clamp along DNA to trap
      supercoils) suggests that this is unlikely to be the explanation for the effect.
      We conclude that geometric selection of DNA segments by the enzymes is likely to
      be a primary source of the effect, but that it is possible that other kinetic
      factors contribute. We also speculate whether topology simplification might
      simply be an evolutionary relic, with no adaptive significance.

PMID- 19094995
TI  - Orchestration of Haemophilus influenzae RecJ exonuclease by interaction with
      single-stranded DNA-binding protein.
AB  - RecJ exonuclease plays crucial roles in several DNA repair and recombination
      pathways, and its ubiquity in bacterial species points to its ancient origin and
      vital cellular function. RecJ exonuclease from Haemophilus influenzae is a 575
      amino-acid protein that harbors the characteristic motifs conserved among RecJ
      homologs. The purified protein exhibits a processive 5'-3' single-stranded-DNA
      specific exonuclease activity. The exonuclease activity of H. influenzae RecJ
      (HiRecJ) was supported by Mg(2+) or Mn(2+) and inhibited by Cd(2+), suggesting a
      different mode of metal binding in HiRecJ as compared to Escherichia coli RecJ
      (EcoRecJ). Site-directed mutagenesis of highly conserved residues in HiRecJ
      abolished enzymatic activity. Interestingly, substitution of alanine for
      aspartate 77 resulted in a catalytically inactive enzyme that bound to DNA with a
      significantly higher affinity as compared to the wild-type enzyme. Noticeably,
      steady-state kinetic studies showed that H. influenzae single-stranded DNA
      binding protein (HiSSB) increased the affinity of HiRecJ for single-stranded DNA
      and stimulated its exonuclease activity. HiSSB, whose C-terminal tail had been
      deleted, failed to enhance RecJ exonuclease activity. More importantly, HiRecJ
      was found to directly associate with its cognate single-stranded DNA-binding
      protein (SSB), as demonstrated by various in vitro assays. Interaction studies
      carried out with the truncated variants of HiRecJ and HiSSB revealed that the two
      proteins interact via the C-terminus of SSB protein and the core-catalytic domain
      of RecJ. Taken together, these results emphasize direct interaction between RecJ
      and SSB, which confers functional cooperativity to these two proteins. In
      addition, these results implicate SSB as being involved in the recruitment of
      RecJ to DNA and provide insights into the interplay between these proteins in
      repair and recombination pathways.

PMID- 19094997
TI  - The effects of aging on capillary hemodynamics in contracting rat spinotrapezius
      muscle.
AB  - Advancing age alters the structural and functional determinants of convective and
      diffusive muscle oxygen (O(2)) flux. However, capillary red blood cell (RBC)
      hemodynamics have not been investigated during contractions in muscles of old
      animals. Therefore, we tested the hypothesis that aging induces significant
      capillary hemodynamic alterations during electrically-induced contractions in the
      spinotrapezius muscle of old Fischer 344 x Brown Norway rats when compared to
      younger counterparts. The spinotrapezius muscle was observed via intravital
      microscopy under both resting and contracting conditions in 8 old (O: 26-30
      months) and 5 young (Y: 6-8 months) animals. Capillary RBC flux (F(RBC)),
      velocity (V(RBC)), hematocrit (H(CAP)), and lineal F(RBC) (F(RBC) x capillary
      lineal density) were determined in all visible capillaries and fields at rest and
      during the steady-state of muscle contractions. At rest F(RBC) and V(RBC) were
      elevated in O compared to Y rats, while there was no difference in H(CAP) or
      lineal F(RBC) between groups. During the contracting steady-state, Delta F(RBC)
      (Y: 28.8+/-7.7, O: -2.9+/-1.4 cells/s), Delta V(RBC) (Y: 253+/-68, O: -4+/-15
      microm/s), Delta H(CAP) (Y: 0.02+/-0.02, O: -0.03+/-0.01), and the Delta lineal
      F(RBC) (Y: 892+/-255, O: -24+/-30 cells/s/mm) were all lower (P<0.05) in O
      compared to Y rats. These results indicate that despite maintained total
      perfusive and diffusive O(2) transport at rest, advancing age results in
      significant impairments in capillary hemodynamics during electrically-induced
      contractions. These alterations likely contribute to the mechanisms responsible
      for the reduced exercise capacity commonly found in elderly populations.

PMID- 19094998
TI  - TREX2 exonuclease defective cells exhibit double-strand breaks and chromosomal
      fragments but not Robertsonian translocations.
AB  - TREX2 is a 3'-->5' exonuclease that binds to DNA and removes 3' mismatched
      nucleotides. By an in vitro structure function analysis, we found a single amino
      acid change (H188A) completely ablates exonuclease activity and impairs DNA
      binding by about 60% while another change (R167A) impairs DNA binding by about
      85% without impacting exonuclease activity. For a biological analysis, we
      generated trex2null cells by deleting the entire Trex2 coding sequences in mouse
      embryonic stem (ES) cells. We found Trex2 deletion caused high levels of
      Robertsonian translocations (RbTs) showing Trex2 is important for chromosomal
      maintenance. Here we evaluate the exonuclease and DNA binding domains by
      expressing in trex2(null) cells coding sequences for wild type human TREX2
      (Trex2hTX2) or human TREX2 with the H188A change (Trex2H188A) or the R167A change
      (Trex2R167A). These cDNAs are positioned adjacent to the mouse Trex2 promoter by
      Cre-mediated knock-in. By observing metaphase spreads, we found Trex2H188A cells
      exhibited high levels of double-strand breaks (DSBs) and chromosomal fragments.
      Therefore, TREX2 may suppress spontaneous DSBs or exonuclease defective TREX2 may
      induce them in a dominate-negative manner. We also found Trex2hTX2, hTrex2H188A
      and hTrex2R167A cells did not exhibit RbTs. Thus, neither the exonuclease nor DNA
      binding domains suppress RbTs suggesting TREX2 possesses additional biochemical
      activities.

PMID- 19094999
TI  - Atypical saccadic scanning in autistic spectrum disorder.
AB  - Saccadic scanning was examined for typically developing (TD) adults and those
      with autistic spectrum disorder (ASD) during inspection of the 'Repin' picture
      (Yarbus, A. (1967). Eye movements and vision. New York: Plenum) under two
      different viewing instructions: (A) material instructions ('Estimate the material
      circumstances of the family'); and (B) social instructions ('Estimate how long
      the unexpected visitor has been away'). Proportions of fixations and viewing time
      on the people and the objects in the scene differed between the two task
      instructions for TD, but not ASD participants showing that people with ASD did
      not differentially sample the scene according to top down instruction. One
      tentative explanation for these findings is that dysfunctional or underdeveloped
      fronto-parietal feedback systems in ASD, could result in defective saccadic
      sampling strategies, leading to impairments with cognitive processing in ASD.

PMID- 19095000
TI  - Molecular mechanisms of testosterone action in spermatogenesis.
AB  - Testosterone is required for the maturation of male germ cells, the production of
      sperm and thus male fertility. However, the mechanisms by which testosterone
      regulates spermatogenic processes have not been well defined. In this review,
      classical and non-classical pathways of testosterone signaling in the Sertoli
      cells of the testis are discussed in relation to testosterone-regulated processes
      that are required for spermatogenesis.

PMID- 19095003
TI  - Cytotoxicity and ultrastructural changes in H9c2(2-1) cells treated with
      pavetamine, a novel polyamine.
AB  - Intake of pavetamine, a novel polyamine, synthesized by certain rubiaceous
      plants, is the cause of gousiekte ("Quick disease") in ruminants. The disease is
      characterized by a latent period of 4-8 weeks, followed by heart failure. The aim
      of this study was to firstly investigate the cytotoxicity in H9c2(2-1) cells
      using the MTT (3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide)
      and LDH (lactate dehydrogenase) release assays. Maximum cell death occurred after
      pavetamine exposure of cells for 72h at a concentration of 200muM (55%+/-9.84),
      as measured by the MTT assay. LDH release was only observed after 72h exposure to
      pavetamine. Secondly, the ultrastructural changes induced by pavetamine in H9c2(2
      1) cells were investigated. Changes in the mitochondria and sarcoplasmic reticula
      were observed. The nucleus was not affected during the first 48h exposure of
      cells to pavetamine and no chromatin condensation occurred. However, after 72h
      exposure to pavetamine, the nucleus became fragmented and membrane blebbing
      occurred. It was concluded that the ultimate cell death of H9c2(2-1) cells
      treated with pavetamine, was through necrosis and not apoptosis. Thirdly, the
      effect of pavetamine on the mitochondrial membrane potential (DeltaPsi) was
      evaluated by using the JC-1 (5,5',6,6'-Tetrachloro-1,1',3,3'-tetraethyl
      imidacarbocyanine iodide) and TMRM (tetramethylrhodamine methyl ester
      perchlorate) probes. Pavetamine treatment led to significant hyperpolarization of
      the mitochondrial membrane potential. Cyclosporin A (CsA), an inhibitor of the
      mitochondrial permeability transition pore, did not reduce the cytotoxicity of
      pavetamine significantly, indicating that the MPTP (mitochondrial permeability
      transition pore) plays no role in the cytotoxicity of pavetamine.

PMID- 19095001
TI  - In utero and postnatal exposure to arsenic alters pulmonary structure and
      function.
AB  - In addition to cancer endpoints, arsenic exposures can also lead to non-cancerous
      chronic lung disease. Exposures during sensitive developmental time points can
      contribute to the adult disease. Using a mouse model, in utero and early
      postnatal exposures to arsenic (100 ppb or less in drinking water) were found to
      alter airway reactivity to methacholine challenge in 28 day old pups. Removal of
      mice from arsenic exposure 28 days after birth did not reverse the alterations in
      sensitivity to methacholine. In addition, adult mice exposed to similar levels of
      arsenic in drinking water did not show alterations. Therefore, alterations in
      airway reactivity were irreversible and specific to exposures during lung
      development. These functional changes correlated with protein and gene expression
      changes as well as morphological structural changes around the airways. Arsenic
      increased the whole lung levels of smooth muscle actin in a dose dependent
      manner. The level of smooth muscle mass around airways was increased with arsenic
      exposure, especially around airways smaller than 100 microm in diameter. This
      increase in smooth muscle was associated with alterations in extracellular matrix
      (collagen, elastin) expression. This model system demonstrates that in utero and
      postnatal exposure to environmentally relevant levels of arsenic can irreversibly
      alter pulmonary structure and function in the adults.

PMID- 19095002
TI  - Exposure to monomethylarsonous acid (MMA(III)) leads to altered selenoprotein
      synthesis in a primary human lung cell model.
AB  - Monomethylarsonous acid (MMA(III)), a trivalent metabolite of arsenic, is highly
      cytotoxic and recent cell culture studies suggest that it might act as a
      carcinogen. The general consensus of studies indicates that the cytotoxicity of
      MMA(III) is a result of increased levels of reactive oxygen species (ROS). A
      longstanding relationship between arsenic and selenium metabolism has led to the
      use of selenium as a supplement in arsenic exposed populations, however the
      impact of organic arsenicals (methylated metabolites) on selenium metabolism is
      still poorly understood. In this study we determined the impact of exposure to
      MMA(III) on the regulation of expression of TrxR1 and its activity using a
      primary lung fibroblast line, WI-38. The promoter region of the gene encoding the
      selenoprotein thioredoxin reductase 1 (TrxR1) contains an antioxidant responsive
      element (ARE) that has been shown to be activated in the presence of
      electrophilic compounds. Results from radiolabeled selenoproteins indicate that
      exposure to low concentrations of MMA(III) resulted in increased synthesis of
      TrxR1 in WI-38 cells, and lower incorporation of selenium into other
      selenoproteins. MMA(III) treatment led to increased mRNA encoding TrxR1 in WI-38
      cells, while lower levels of mRNA coding for cellular glutathione peroxidase
      (cGpx) were detected in exposed cells. Luciferase activity of TrxR1 promoter
      fusions increased with addition of MMA(III), as did expression of a rat quinone
      reductase (QR) promoter fusion construct. However, MMA(III) induction of the TRX1
      promoter fusion was abrogated when the ARE was mutated, suggesting that this
      regulation is mediated via the ARE. These results indicate that MMA(III) alters
      the expression of selenoproteins based on a selective induction of TrxR1, and
      this response to exposure to organic arsenicals that requires the ARE element.

PMID- 19095004
TI  - Adrenalectomy modifies the hippocampal 5-HT(1A) receptors and the anxiolytic-like
      effect of 8-OH-DPAT in rats.
AB  - Stress is closely related with levels of corticosteroid and corticotrophin
      releasing factor, which at the same time can modify 5-HT(1A) receptors and brain
      serotonin levels. Consequently, the absence of corticosteroids in rats induced by
      an adrenalectomy could be useful to understand the functionality of the brain
      serotonergic system after a stressing event. The influence of 15 min of forced
      swimming was explored on sham and adrenalectomized rats by measuring the 5-HT(1A)
      receptor density in raphe and hippocampus. Other previously stressed groups (sham
      and adrenalectomized) were tested in two anxiety models with the 5-HT(1A) agonist
      8-OH-DPAT, the postsynaptic antagonist MM-77, and with a combination of these two
      compounds. It was found that the removal of adrenals in rats that were not
      previously stressed induced an increase in the postsynaptic 5-HT(1A) receptor
      density. On the other hand, an adrenalectomy in rats that were previously
      stressed induced a reduction in the same receptor density. Adrenal gland removal
      induced an anxiolytic-like effect. However, after the injection of 8-OH-DPAT,
      adrenalectomized rats showed anxiogenic-like actions, an effect which was
      reversed by MM-77. Data show that changes in 5-HT(1A) receptors density caused by
      a stressful session can have behavioral consequences, thus emphasizing the need
      to reconsider the clinical use of 5-HT(1A) ligands after traumatic events.

PMID- 19095005
TI  - New molecular components supporting ryanodine receptor-mediated Ca(2+) release:
      roles of junctophilin and TRIC channel in embryonic cardiomyocytes.
AB  - Ca(2+) mobilization from intracellular stores is mediated by Ca(2+) release
      channels, designated ryanodine and IP(3) receptors, and directly regulates
      important cellular reactions including muscle contraction, endo/exocrine
      secretion, and neural excitability. In order to function as an intracellular
      store, the endo/sarcoplasmic reticulum is equipped with cooperative Ca(2+)
      uptake, storage and release machineries, comprising synergic collaborations among
      integral-membrane, cytoplasmic and luminal proteins. Our recent studies have
      demonstrated that junctophilins form junctional membrane complexes between the
      plasma membrane and the endo/sarcoplasmic reticulum in excitable cells, and that
      TRIC (trimeric intracellular cation) channels act as novel monovalent cation
      specific channels on intracellular membrane systems. Knockout mice have provided
      evidence that both junctophilins and TRIC channels support efficient ryanodine
      receptor-mediated Ca(2+) release in muscle cells. This review focuses on cardiac
      Ca(2+) release by discussing pathological defects of mutant cardiomyocytes
      lacking ryanodine receptors, junctophilins, or TRIC channels.

PMID- 19095006
TI  - Differences in EMG spike shape between individuals with and without non-specific
      arm pain.
AB  - The purpose of this study was to determine whether spike shape analysis of
      surface electromyographic (SEMG) activity is a useful tool to study muscle
      disorders. This study investigated SEMG spike shape parameters at low levels of
      contraction and changes in SEMG spike shape across different levels of isometric
      wrist extension contractions in individuals with non-specific arm pain (NSAP),
      asymptomatic subjects deemed at-risk for repetitive strain injury, and
      asymptomatic control subjects. Twenty-two asymptomatic control subjects, 8 at
      risk subjects, and 16 subjects with NSAP participated. Bipolar SEMG data were
      recorded from the ECRB muscle during isometric wrist extension contractions at
      10, 20, 30, 40, 50, 60, and 70% of maximum voluntary contraction (MVC) force
      performed in a randomized order. Five criterion measures: mean spike amplitude
      (MSA), mean spike duration (MSD), mean spike slope (MSS), mean spike frequency
      (MSF), and mean number of peaks per spike (MNPPS) were computed from each SEMG
      signal. A one-way analysis of covariance (ANCOVA) of the spike shape parameters
      computed from the 10% MVC data, with group as a main effect and age as a
      covariate, revealed a significant group by age interaction for MSA, and
      significant group main effects for MSS and MNPPS, where the NSAP group had lower
      MSS and lower MNPPS than the control subjects. An ANCOVA including group as a
      main effect and contraction level and age as covariates revealed that all three
      groups showed predictable changes in the spike shape analysis criterion measures
      over increasing contraction force levels, where motor unit recruitment and rate
      coding appear to be the primary mechanisms for increasing force output of the
      muscle. Significant interactions between group and contraction level were
      observed for MSD, MSA, MSS, and MNPPS. The NSAP group presented with differences
      in how the spike shape measures change with increasing contraction level that may
      be indicative of myogenic changes, a result that is consistent with previous
      quantitative EMG findings. This work provides evidence that NSAP involves
      myogenic changes in the ECRB muscle and that spike shape analysis may be a
      valuable non-invasive tool in the evaluation of neuromuscular disorders.

PMID- 19095007
TI  - Identification of measles virus epitopes using an ultra-fast method of panning
      phage-displayed random peptide libraries.
AB  - Phage-displayed random peptide libraries, in which high affinity phage peptides
      are enriched by repetitive selection (panning) on target antibody, provide a
      unique tool for identifying antigen specificity. This paper describes a new
      panning method that enables selection of peptides in 1 day as compared to about 6
      days required in traditional panning to identify virus-specific epitopes. The
      method, termed ultra-fast selection of peptide (UFSP), utilizes phage produced by
      bacterial infection (phage amplification) directly for subsequent panning. Phage
      amplified in less than 1h of infection in Escherichia coli are used for binding
      to target antibody pre-coated in the same wells of an ELISA plate, obviating the
      need for traditional large-scale amplification and purification. Importantly,
      phage elution at 37 degrees C was superior to that at room temperature, and phage
      amplification in a 150-microl volume of E. coli cells was superior to that in 250
      microl volume. Application of UFSP to two monoclonal antibodies generated from
      clonally expanded plasma cells in subacute sclerosing panencephalitis (SSPE)
      brain identified high-affinity measles virus-specific-peptide epitopes. The UFSP
      panning methodology will expedite identification of peptides reacting with
      antibodies generated in other diseases of unknown antigenic specificity such as
      multiple sclerosis (MS), sarcoidosis and Behcet's disease.

PMID- 19095008
TI  - Improvements in the detection of small ruminant lentivirus infection in the blood
      of sheep by PCR.
AB  - The polymerase chain reaction on blood samples has been considered a complement
      to serological methods for the detection of small ruminant lentiviruses (SRLV)
      infections in sheep and goats. This is a report on the results of a study to
      evaluate the use of the same blood sample for the detection of infected animals
      by ELISA and PCR. A comparison between the results obtained by applying PCRs
      targeting LTR and gag sequences on blood clot, serum and peripheral blood
      leucocytes was made. In addition to simplifying sampling and laboratory work, the
      use of blood clot samples with the gag-PCR improved remarkably the detection of
      infected animals. Finally, this study has shown the existence of a cell-free
      viremia in the serum of SRLV-infected sheep.

PMID- 19095009
TI  - Isolation of RNA from cell lines and cervical cytology specimens stored in BD
      SurePath preservative fluid and downstream detection of housekeeping gene and HPV
      E6 expression using real time RT-PCR.
AB  - This study was performed to demonstrate that RNA isolated from cell lines and
      cervical cytology specimens stored in SurePath preservative fluid would be
      functional in real-time RT-PCR assays. RNA was isolated from cervical cell lines
      or cytology samples stored in SurePath preservative at room temperature for 2-5
      weeks using five commercially available RNA purification kits, three of which
      contain proteinases. The quality of the RNA was assessed by real time RT-PCR
      amplification of GAPDH, GUSB, U1A, HPV 16 and 18 E6 mRNAs. RNA was isolated
      successfully from cells that were stored in SurePath preservative fluid with only
      the three protocols that contained proteinases. GAPDH was amplified in 98-100% of
      the samples, GUSB in 90-98%, and the least abundant transcript, U1A, was
      amplified in 81-96% of the samples. HPV 16 and 18 E6 transcripts were detected in
      56% of high grade, 39% of low grade and 2% of normal samples, with a concordance
      between DNA genotype and E6 mRNA expression of 97%. We demonstrated that RNA can
      be extracted from cervical cell lines and cytology specimens stored in BD
      SurePath preservative fluid with three different procedures that all contain
      proteinases. This RNA is suitable for real-time RT-PCR applications.

PMID- 19095010
TI  - Development of a hamster kidney cell line expressing stably T7 RNA polymerase
      using retroviral gene transfer technology for efficient rescue of infectious foot
      and-mouth disease virus.
AB  - Reverse genetics systems, with the ability to manipulate viral genomes at the DNA
      molecular level, are an important platform for study of the assembly and function
      of viruses. Genome manipulation, such as gene recombination, mosaicism, and
      mutation may interfere with replication, assembly and release of viruses. An
      efficient, convenient and economical method of virus rescue is undoubtedly
      required for increasing the efficiency of rescuing recombinant viruses. To
      develop an efficient, helper virus-free viral recovery system (reverse genetics),
      a retroviral gene transfer technology was used to establish a stable BHK-21 cell
      line (designated as BHKT7) which expressed constitutively bacteriophage T7 RNA
      polymerase (T7 RNAP). An improved method for rescue of infectious foot-and-mouth
      disease virus (FMDV) was then developed. FMDV full-length cDNA under control of a
      T7 promotor, was transfected into BHKT7 of differing passages. FMDV virus was
      rescued efficiently from the BHKT7 cells, the passage number not having an effect
      on the efficiency of recovery. As a result, the cell line was stable even after
      multiple passages, expressing sufficient T7 RNAP to support ex vivo transcription
      and efficient rescue. The reverse genetics system described below is efficient,
      stable, and convenient. The system could provide not only the basis of gene
      function research into FMDV, but could also be used for reverse genetics research
      into other positive-strand RNA viruses, without the need for helper viruses.

PMID- 19095011
TI  - The emergence of consciousness in phylogeny.
AB  - The brains of animals show chemical, anatomical, and functional differences, such
      as dopamine production and structure of sleep, between Amniota and older groups.
      In addition, play behavior, capacity to acquire taste aversion, sensory pleasure
      in decision making, and expression of emotional tachycardia and fever started
      also to be displayed by Amniota, suggesting that the brain may have began to work
      differently in early Amniota than in Lissamphibia and earlier vertebrates. Thus
      we propose that emotion, and more broadly speaking consciousness, emerged in the
      evolutionary line among the early Amniota. We also propose that consciousness is
      characterized by a common mental pathway that uses pleasure, or its counterpart
      displeasure, as a means to optimize behavior.

PMID- 19095012
TI  - Social laterality and 'transversality' in two species of mangabeys: influence of
      rank and implication for hemispheric specialization.
AB  - Individuals in social groups monitor many relationships by adapting their
      activities to the sex, age, social status, behaviour as well as the position of
      conspecifics. Here, we investigated the influence of the relative positions of
      the members of two groups of mangabeys on social visual laterality (right/left)
      and 'transversality' (frontal/rear) in two contexts: (1) 'one-to-one'
      interactions and (2) a 'one-to-many' context allowing potential observation of
      all group members. We discuss our data in relation to (1) the influence of rank
      and (2) theories explaining lateralization of cerebral hemispheres. First, in
      'one-to-one' situations, members of both groups were approached more frequently
      from their left than from their right, and red-capped mangabeys approached a
      group member more frequently from their right than from their left. In 'one-to
      many' situations, red-capped mangabeys kept more group members in their right
      than their left frontal visual field. Conversely, the social 'transversality'
      bias was the same in both contexts: the frontal field was favoured. Second,
      approach side and relative positions differed according to social rank. Mangabeys
      that were approached more frequently from their left ranked relatively high. The
      higher an individual ranked, the more it left other group members behind it; on
      the contrary dominated mangabeys generally remained below other group members.
      Thus, social structures, as well as relationships within a group, appear to be
      good candidates to explain social laterality and 'transversality'.

PMID- 19095014
TI  - Contribution of intracellular Ca2+ stores to Ca2+ signaling during chemokinesis
      of human neutrophil granulocytes.
AB  - Extracellular agonists increase the cytosolic free Ca2+ concentration ([Ca2+]c)
      by Ca2+ influx and by stimulating Ca2+ release from intracellular stores, mainly
      the endoplasmic reticulum and to a lesser extent also later compartments of the
      secretory pathway, particularly the Golgi. The Golgi takes up Ca2+ via
      Sarco/Endoplasmic Reticulum Ca2+ATPases (SERCAs) and the Secretory-Pathway
      Ca2+ATPases (SPCAs). The endogenous expression of SERCAs and SPCAs neutrophils
      was demonstrated by Western blotting and immunocytochemistry. Up till now, all
      cytosolic Ca2+ transients due to intracellular Ca2+ release have been found to
      originate from SERCA-dependent stores. We found that human neutrophils also
      present Ca2+ release from a SERCA-independent store. Changes in [Ca2+]c of
      neutrophils were investigated during chemokinesis induced by chemotactic factors
      in Ca2+-free solution with and without the SERCA-specific inhibitor thapsigargin.
      Using N-formyl-methionyl-leucyl-phenylalanine or interleukin-8 as agonists, Ca2+
      release from intracellular stores was observed in respectively about 40% and 20%
      of the neutrophils pre-treated with Ca2+-free solution and thapsigargin. In the
      latter condition, 20-30% of the cells preserved migratory behaviour. These
      results indicate that both SERCA-dependent and SERCA-independent (presumably SPCA
      dependent) intracellular Ca2+ stores contribute to Ca2+ signaling during
      chemokinesis of human neutrophil granulocytes.

PMID- 19095013
TI  - Proteomic analysis of Schistosoma mansoni proteins released during in vitro
      miracidium-to-sporocyst transformation.
AB  - Free-living miracidia of Schistosoma mansoni, upon penetration of the their snail
      intermediate host, undergo dramatic morphological and physiological changes as
      they transform to the parasitic sporocyst stage. During this transformation
      process, developing larvae release a diverse array of proteins, herein referred
      to as larval transformation proteins (LTPs), some of which are postulated to
      serve a parasite protective function. In the present study, nanoLC-tandem MS
      analysis was performed on all proteins represented in entire 1-dimensional SDS
      PAGE-separated samples in order to gain a more comprehensive picture of the
      protein constituents associated with miracidium-to-sporocyst transformation and
      thus, their potential role in influencing establishment of intramolluscan
      infections. Of 127 proteins with sufficient peptide/sequence information,
      specific identifications were made for 99, while 28 represented unknown or
      hypothetical proteins. Nineteen percent of identified proteins possessed signal
      peptides constituting a cohort of classical secretory proteins, while 22% were
      identified as putative nonclassically secreted leaderless proteins based on
      SecretomeP analysis. Proteins comprising these groups consisted mainly of
      proteases/protease inhibitors, small HSPs, redox/antioxidant enzymes, ion-binding
      proteins including those with anti-oxidant Fe-binding activities (ferritins, heme
      binding protein), and venom allergen-like (VAL) proteins. A polyclonal antibody
      generated against whole LTPs recognized proteins primarily associated with the
      cilia, ciliated epidermal plates and intercellular ridges of miracidia and the
      tegument of fully transformed sporocysts, identifying these structures as sources
      of a subset of LTPs. Thus lysis of plates and/or leakage during formation of the
      sporocyst syncytium likely represent significant contributors to the overall LTP
      makeup, especially identified nonsecretory proteins. However, as plate
      release/degradation and tegument formation are part of the normal developmental
      process, all LTPs regardless of tissue origin, would be expected at the parasite
      host interface upon infection. This study significantly expands the repertoire of
      LTPs associated with larval transformation and identifies several, e.g., those
      involved in stress responses, proteolysis/inhibition, antioxidant and
      detoxication, and immune modulation, that may play a parasite protective role
      during this crucial period of transition.

PMID- 19095015
TI  - ClassRHO: a platform for classification of bacterial rieske non-heme iron ring
      hydroxylating oxygenases.
AB  - We have developed an easy-to-use multiplatform classification tool, ClassRHO,
      which facilitates classification and comparison of bacterial Rieske non-heme iron
      aromatic ring-hydroxylating oxygenases (RHOs). Visualization and analysis can be
      generated on-the-fly by entering or uploading RHO query sequences. Pre-computed
      classifications were implemented for 42 standard RHO sequences. These 42 RHO
      sequences can be flexibly selected based on user requests. ClassRHO provides
      users with many options to view and analyze RHO sequences.

PMID- 19095016
TI  - Response inhibition and interference control in children with AD/HD: a visual ERP
      investigation.
AB  - Children with Attention-deficit Hyperactivity Disorder (AD/HD) show deficits in
      executive inhibitory functions such as behavioral inhibition and interference
      control, but investigations of both of these domains in the same groups of
      children is scarce, especially with concurrent consideration of ERP indices of
      inhibitory processes. Twenty children with AD/HD and 20 matched controls aged
      between 8 and 14 years performed visual Go-Nogo (30% Nogo) and Flanker tasks
      while EEG was recorded. Results indicated that children with AD/HD traded off
      speed for accuracy in the Go-Nogo task, resulting in similar levels of response
      inhibition accuracy; in the Flanker task response speed and errors were at
      control levels, while misses were increased and showed an enhanced interference
      effect. In the Go-Nogo task, the AD/HD group showed reduced Go/Nogo P2, a reduced
      central N2 Nogo>Go effect, and a more anterior Go/Nogo P3 compared to controls.
      For the Flanker task, the AD/HD group showed delayed N1 and P2, dramatically
      reduced N2 to Incongruent stimuli, enhanced N2 to Neutral stimuli, as well as
      increased P3 to Incongruent stimuli, compared to controls. These results indicate
      that Go-Nogo behavioral inhibition and Flanker interference control were not
      equally impaired in children with AD/HD, and that factors such as effort, arousal
      and motivation require further investigation.

PMID- 19095017
TI  - Engineering of pyranose 2-oxidase: improvement for biofuel cell and food
      applications through semi-rational protein design.
AB  - Pyranose 2-oxidase (P2Ox) has several proposed biotechnological applications such
      as a bio-component in biofuel cells or for carbohydrate transformations. To
      improve some of the catalytic properties of P2Ox from Trametes multicolor, we
      selected a semi-rational approach of enzyme engineering, saturation mutagenesis
      of active-site residues and subsequent screening of mutant libraries for improved
      activity. One of the active-site mutants with improved catalytic characteristics
      identified was V546C, which showed catalytic constants increased by up to 5.7
      fold for both the sugar substrates (D-glucose and D-galactose) and alternative
      electron acceptors (1,4-benzoquinone, BQ and ferricenium ion, Fc(+)], albeit at
      the expense of increased Michaelis constants. By combining V546C with other amino
      acid replacements, we obtained P2Ox variants that are of interest for biofuel
      cell applications due to their increased k(cat) for both BQ and Fc(+), e.g.,
      V546C/E542K showed 4.4- and 17-fold increased k(cat) for BQ compared to the wild
      type enzyme when D-glucose and D-galactose, respectively, were the saturating
      substrates, while V546C/T169G showed approx. 40- and 50-fold higher k(cat) for BQ
      and Fc(+), respectively, with D-galactose in excess. This latter variant also
      shows significantly modulated sugar substrate selectivity, due to an increase in
      k(cat)/K(M) for D-galactose and a decrease in k(cat)/K(M) for D-glucose when
      oxygen is the electron acceptor, as well as improved catalytic efficiencies for d
      galactose, regardless of the electron acceptor used. While the wild-type enzyme
      strongly prefers D-glucose over D-galactose as its substrate, V546C/T169G
      converts both sugars equally well as was shown by the kinetic constants
      determined as well as by biotransformation experiments.

PMID- 19095019
TI  - Complex expression control of the Corynebacterium glutamicum aconitase gene:
      identification of RamA as a third transcriptional regulator besides AcnR and
      RipA.
AB  - Expression of the aconitase gene acn of Corynebacterium glutamicum was previously
      shown to be repressed by the TetR-type regulator AcnR in response to a yet
      unknown stimulus and by the AraC-type regulator RipA in response to iron
      limitation. Here we have identified a third transcriptional regulator of
      aconitase, RamA. The RamA protein was enriched by DNA affinity chromatography
      with the acn promoter region from protein extracts of acetate-grown cells but not
      or only weakly from extracts of glucose-grown cells. In the wild type, aconitase
      activity is about 3-fold higher in acetate-grown cells compared to glucose-grown
      cells. In extracts of a ramA deletion mutant, acetate-grown cells possess the
      same aconitase activity as glucose-grown cells. Inspection of the acn promoter
      region led to the identification of a RamA binding motif (TGGGGGTGAGTAAGGGGGT),
      which was shown by electrophoretic mobility shift assays to be essential for
      binding of purified RamA. Furthermore, the functional relevance of this motif,
      which is located -180 to -162bp upstream of the transcriptional start site, for
      RamA-dependent activation of acn expression was confirmed by promoter fusion
      assays. Thus, RamA was shown to be responsible for activation of acn expression
      in the presence of acetate. Furthermore, evidence was obtained in this work that
      RamB negatively regulates acn expression, but in an indirect manner.

PMID- 19095018
TI  - Analysis of the secretome of the soybean symbiont Bradyrhizobium japonicum.
AB  - Proteins from the supernatant of Bradyrhizobium japonicum were separated by two
      dimensional gel electrophoresis and stained with Coomassie. This revealed more
      than 100 protein spots. Sixty-eight proteins were identified by mass
      spectrometry. Thirty-five are predicted to contain an N-terminal signal peptide
      characteristic for proteins transported by the general secretory pathway. Most of
      these appear to be substrate-binding proteins of the ABC transporter family. Ten
      proteins were categorized as unclassified conserved or hypothetical. None of the
      proteins has similarity to proteins transported by a type I secretion system or
      to autotransporters. Three of the proteins might be located in the outer
      membrane. The addition of genistein led to changes in the spot pattern of three
      flagellar proteins and resulted in the identification of the nodulation outer
      protein Pgl. Moreover, the application of shot-gun mass spectrometry resulted in
      the first-time identification of NopB, NopH and NopT, which were present only
      after genistein induction. Replacing genistein with daidzein or coumestrol
      reduced the amount of the type III-secreted protein GunA2.

PMID- 19095020
TI  - Targeting a c-Myc inhibitory polypeptide to specific intracellular compartments
      using cell penetrating peptides.
AB  - The therapeutic index of current anti-cancer chemotherapeutics can be improved by
      two major mechanisms: 1) developing drugs which are specifically toxic to the
      cancer cells and 2) developing methods to deliver drugs to the tumor site. In an
      attempt to combine these approaches, we developed a thermally responsive
      polypeptide inhibitor of c-Myc. This polypeptide is based on the thermally
      responsive Elastin-like polypeptide (ELP). When injected systemically, ELP-fused
      drugs will aggregate and accumulate at the tumor site where local hyperthermia is
      applied. ELP was fused to a peptide which blocks c-Myc/Max dimerization (H1),
      thereby inhibiting transcription activation by c-Myc (ELP-H1). In this study, the
      cellular uptake, intracellular distribution, and potency of the Pen, Tat and Bac
      cell penetrating peptides fused to ELP-H1 were evaluated. While Pen-ELP-H1 and
      Tat-ELP-H1 were localized in the cytoplasm, Bac-ELP-H1 localized to the nucleus
      in a subset of the cells and was the most potent inhibitor of MCF-7 cell
      proliferation. This data demonstrates that ELP can be targeted to the desired
      cellular compartment simply by choice of the CPP used, resulting in a more potent
      nuclear targeted c-Myc inhibitory polypeptide which may be beneficial in cancer
      therapy.

PMID- 19095022
TI  - Synergistic antitumor activity of metronomic dosing of cyclophosphamide in
      combination with doxorubicin-containing PEGylated liposomes in a murine solid
      tumor model.
AB  - Cyclophosphamide (CPA) and doxorubicin (DXR)-containing sterically stabilized
      liposomes (DXR-SL) have a proven clinical activity. We propose that a metronomic
      CPA dosing schedule enhances accumulation of DXR-SL in solid tumors, because it
      causes apoptosis in the endothelial cells of the growing tumor vasculature and
      thereby may increase the permeability of the tumor microvessels. To establish the
      validity of this hypothesis we investigated the therapeutic benefits of
      metronomic CPA dosing (p.o.) combined with DXR-SL (i.v.) in a Lewis lung
      carcinoma, subcutaneously growing in C57BL/6 mouse. The metronomic CPA dosing
      clearly promoted accumulation and subsequent deep diffusion of SL in the solid
      tumor as a result of rather a transient increase in the density of CD31(+)
      microvessels, which shows high permeability to SL. It appears that the enhancing
      effect of metronomic CPA dosing is strongly dependent on the dose of CPA as well
      as on the time at which the treatment was initiated. Our study indicates that the
      use of metronomic chemotherapy combined with nanocarriers may be of significant
      clinical and practical importance in treating intractable solid tumors.

PMID- 19095021
TI  - Complexation hydrogels for intestinal delivery of interferon beta and calcitonin.
AB  - Recent studies have suggested that complexation hydrogels poly(methacrylic acid-g
      ethylene glycol) (henceforth designated as P(MAA-g-EG)) exhibit high insulin
      incorporation efficiency, rapid insulin release in the intestine based on their
      pH-dependent complexation properties, enzyme-inhibiting effects and mucoadhesive
      characteristics. Therefore, they are promising carriers for insulin delivery via
      an oral route. As we designed these hydrogels as carriers suitable for oral
      administration of various peptide/protein drugs, in this study we aimed at
      investigating the applicability of P(MAA-g-EG) hydrogels to improving the
      intestinal absorption of various peptide/protein drugs. High loading efficiency
      into hydrogels was observed for insulin, calcitonin, and interferon beta. In
      addition, polymer microparticles loaded with calcitonin and interferon beta
      exhibited complexation/decomplexation and pH-sensitive release behavior. The
      molecular weight and chemical structure appeared to affect the efficiency of
      loading and release depending on the peptides and proteins. Furthermore, a
      drastic reduction of plasma calcium concentration accompanied by calcium
      absorption and a dose-dependent enhancement of plasma interferon beta
      concentration were observed after the administration of particles loaded with
      calcitonin or interferon beta into closed rat ileal segments. These findings
      indicate that P(MAA-g-EG) hydrogels are promising carriers for administration of
      various peptides and proteins via an oral route.

PMID- 19095023
TI  - Neuropeptide Y and CGRP concentrations in the rat tail artery: Effects of age and
      two types of diabetes.
AB  - The changes in concentrations of two neuropeptides, neuropeptide Y (NPY) and
      calcitonin gene-related peptide (CGRP) in different segments of the rat tail
      artery have been investigated (a) after 12 and 16 weeks of streptozotocin (STZ)
      induced hyperglycemia that has been induced at the age of 10 weeks, and (b) in 52
      week-old Goto-Kakizaki (GK) rats that were intolerant of glucose, and age-matched
      Wistar controls. In the control animals at 22, 26 and 52 weeks of age, the
      concentration of CGRP was significantly greater in distal, relative to proximal,
      segments of normal arteries, and this contrasted with the pattern of distribution
      of NPY, which was consistently greater in the proximal than the distal segments.
      STZ-induced diabetes caused significant reductions in the concentrations of NPY
      and CGRP in the middle and distal segments of the vessel after 12 and 16 weeks of
      hyperglycemia. In the glucose-intolerant Goto-Kakizaki (GK) rats, the
      noradrenalin and adrenalin levels increased significantly in the distal segment
      of the artery relative to controls; in contrast there was a significant fall in
      dopamine concentration. The only significant change in the level of NPY in 52
      week-old GK rats was an increase in the proximal segment, suggesting that in Type
      II pre-diabetes, noradrenalin and its co-transmitter NPY are affected
      independently. The concentration of CGRP increased significantly in all segments
      of the artery of the 12-month-old GK rats relative to controls. The similarities
      and differences between these measurements in Type I and Type II diabetic models
      are discussed.

PMID- 19095024
TI  - Efficacy of live attenuated influenza vaccine in children: A meta-analysis of
      nine randomized clinical trials.
AB  - Nine randomized clinical trials, including approximately 25,000 children aged 6
      71 months and 2000 children aged 6-17 years, have evaluated the efficacy of live
      attenuated influenza vaccine (LAIV) against culture-confirmed influenza as
      compared to placebo or trivalent inactivated vaccine (TIV). We conducted meta
      analyses, based on Mantel-Haenszel relative risks from fixed effect models, to
      provide an estimate of vaccine efficacy (VE). Relative to placebo, year 1 VE for
      two doses in vaccine-naive young children was 77% (95% CI: 72%, 80%; P<0.001)
      against antigenically similar strains and 72% against strains regardless of
      antigenic similarity. Efficacy was 85%, 76%, and 73% against antigenically
      similar A/H1N1, A/H3N2, and B, respectively. Year 1 VE of one dose against
      antigenically similar strains in vaccine-naive children was 60%; efficacy of one
      dose in previously vaccinated children in year 2 of the various studies was 87%.
      In head-to-head trials comparing two doses of TIV and LAIV, vaccine-naive
      children who received two doses of LAIV experienced 46% fewer cases of influenza
      illness caused by antigenically similar strains. Similarly, for studies including
      older children who had been previously vaccinated, those receiving one LAIV dose
      experienced 35% fewer cases of influenza illness than those receiving one TIV
      dose. LAIV showed high VE versus placebo with no evidence of difference by age or
      by circulating subtype. In these studies, LAIV was more effective than TIV.

PMID- 19095025
TI  - Prospects and challenges with introduction of a mono-valent meningococcal
      conjugate vaccine in Africa.
AB  - Epidemic meningococcal meningitis is a priority disease for prevention and
      control in Africa. The current World Health Organization (WHO) approach to the
      control of meningitis epidemics is based on early detection of cases and
      emergency vaccination of the population at risk with meningococcal polysaccharide
      (PS) vaccines. But this is a tall order for the developing nations of Africa
      where experts operate from an ineffective health system. Although the widespread
      use of meningococal polysaccharide vaccines has had a major and much appreciated
      public health impact on the disease it has not prevented epidemics of this
      dreaded infection. The current partnership between WHO and the PATH aims to
      develop, evaluate and introduce an appropriate and affordable meningococcal
      conjugate vaccine that could potentially provide for a means of preventing
      epidemic meningitis caused by N. meningitidis group A. In this paper, we review
      the prospects and challenges facing the introduction of the mono-valent conjugate
      vaccine in Africa.

PMID- 19095026
TI  - A vaccine candidate of attenuated genotype VII Newcastle disease virus generated
      by reverse genetics.
AB  - Genotype VII Newcastle disease virus (NDV) has been documented as the predominant
      epidemic genotype in China and some other Asian countries since 1990s. Recent
      work has demonstrated that NDV vaccines phylogenetically closer to epidemic
      viruses provide better protection than conventional vaccines in terms of reducing
      virus shedding and transmission. Since there is currently no available vaccine
      which possesses a close antigenic relationship to the prevalent virulent NDV, a
      new vaccine to protect against the infection of this genotype NDV is in urgent
      need. Here, we describe the generation of a pathogenicity-attenuated genotype VII
      NDV (NDV/ZJ1HN) from a velogenic NDV by mutating the velogenic amino acid motif
      at the F protein cleavage site using reverse genetics techniques. The attenuated
      pathogenicity of NDV/ZJ1HN was confirmed by examination of mean death time (MDT)
      in embryonated eggs and intracerebral pathogenicity index (ICPI) in day-old
      chickens. Subsequently, 2 weeks old birds were immunized with live and
      inactivated NDV/ZJ1HN-based vaccines and challenged 3 or 4 weeks post
      immunization with a lethal dose of a virulent genotype VII NDV strain. Results
      showed that NDV/ZJ1HN effectively protected the vaccinated birds from morbidity
      and mortality against genotype VII virus challenge and significantly reduced
      virus shedding from the vaccinated birds when compared with La Sota vaccinated
      animals, suggesting that NDV/ZJ1HN is a promising vaccine candidate for the
      control of current ND epidemic in China.

PMID- 19095027
TI  - Challenge studies in Rhesus monkeys immunized with candidate hepatitis E
      vaccines: DNA, DNA-prime-protein-boost and DNA-protein encapsulated in liposomes.
AB  - Complete ORF2 gene (1983bp) of hepatitis E virus (HEV) and the 450bp region
      within ORF2 containing neutralizing epitope (NE) cloned in pVAX1 and
      corresponding proteins expressed in baculovirus and prokaryotic systems
      respectively were evaluated as vaccine candidates. Two doses of liposome
      encapsulated DNA plus corresponding protein with both ORF2 and NE regions (Lipo
      ORF2-DP and Lipo-NE-DP) showed 100% seroconversion and comparable anti-HEV titres
      in Swiss albino mice. These vaccine candidates were further evaluated as DNA, DNA
      prime-protein-boost (DPPB) and liposome formulations in Rhesus monkeys. Monkeys
      receiving ORF2/NE DNA seroconverted after fourth dose while those immunized
      employing ORF2-DPPB format seroconverted at 7 weeks post third dose. In view of
      the delayed weak antibody response, these monkeys were not challenged. Though
      Lipo-ORF2-DP was immunogenic, 2 of the 4 monkeys developed HEV infection
      following homologous virus challenge of 100 Monkey Infectious Dose(50). Both
      monkeys immunized with Lipo-NE-DP and 1 of the 2 monkeys immunized with NE-DPPB
      showed complete protection, the second monkey being protected from hepatitis with
      limited viral replication. Irrespective of the type of immunogen, all challenged
      monkeys were protected from hepatitis. The results document Lipo-NE-DP to be a
      promising vaccine candidate needing further evaluation.

PMID- 19095028
TI  - Reduced reaction frequencies with repeated inactivated or live-attenuated
      influenza vaccination.
AB  - Data collected as part of a multi-year trial examining the efficacies of
      inactivated and live-attenuated influenza vaccines were used to evaluate the
      reported occurrence of post-vaccination reactions. Two cohorts were defined: (1)
      individuals who received the same vaccine over two consecutive years, and (2)
      individuals who first enrolled in year 2 of the study and received vaccine only
      in that year. For both vaccines there were significantly fewer reactions reported
      in year 2 in those subjects who were vaccinated both years. Declines were
      demonstrated when comparing year 1 and 2 reaction frequencies in subjects
      vaccinated both years, and differences were seen when comparing year 2 reaction
      frequencies in subjects vaccinated both years with those first vaccinated in year
      2. Reaction reporting peaked on post-vaccination days 0 and 1 following receipt
      of the inactivated vaccine, and on day 2 following receipt of the live-attenuated
      vaccine.

PMID- 19095029
TI  - A prime/boost DNA/Modified vaccinia virus Ankara vaccine expressing recombinant
      Leishmania DNA encoding TRYP is safe and immunogenic in outbred dogs, the
      reservoir of zoonotic visceral leishmaniasis.
AB  - Previous studies demonstrated safety, immunogenicity and efficacy of DNA/modified
      vaccinia virus Ankara (MVA) prime/boost vaccines expressing tryparedoxin
      peroxidase (TRYP) and Leishmania homologue of the mammalian receptor for
      activated C kinase (LACK) against Leishmania major challenge in mice, which was
      consistent with results from TRYP protein/adjuvant combinations in non-human
      primates. This study aimed to conduct safety and immunogenicity trials of these
      DNA/MVA vaccines in dogs, the natural reservoir host of Leishmania infantum,
      followed-up for 4 months post-vaccination. In a cohort of 22 uninfected outbred
      dogs, blinded randomised administration of 1000 microg (high dose) or 100 microg
      (low dose) DNA prime (day 0) and 1x10(8)pfu MVA boost (day 28) was shown to be
      safe and showed no clinical side effects. High dose DNA/MVA vaccinated TRYP dogs
      produced statistically higher mean levels of the type-1 pro-inflammatory cytokine
      IFN-gamma than controls in whole blood assays (WBA) stimulated with the
      recombinant vaccine antigen TRYP, up to the final sampling at day 126, and in the
      absence of challenge with Leishmania. TRYP vaccinated dogs also demonstrated
      significantly higher TRYP-specific total IgG and IgG2 subtype titres than in
      controls, and positive in vivo intradermal reactions at day 156 in the absence of
      natural infection, observed in 6/8 TRYP vaccinated dogs. No significant increases
      in IFN-gamma in LACK-stimulated WBA, or in LACK-specific IgG levels, were
      detected in LACK vaccinated dogs compared to controls, and only 2/9 LACK
      vaccinated dogs demonstrated DTH responses at day 156. In all groups, IgG1
      subclass responses and antigen-specific stimulation of IL-10 were similar to
      controls demonstrating an absence of Th2/T(reg) response, as expected in the
      absence of in vivo restimulation or natural/experimental challenge with
      Leishmania. These collective results indicate significant antigen-specific type-1
      responses and in vivo memory phase cellular immune responses, consistent with
      superior potential for protective vaccine immunogenicity of DNA/MVA TRYP over
      LACK.

PMID- 19095030
TI  - Isolation of antibodies specific to a single conformation-dependant antigenic
      determinant on the EG95 hydatid vaccine.
AB  - EG95 is a recombinant vaccine protein that elicits protection against hydatid
      disease in sheep. Previous studies have shown that the host-protective epitopes
      on EG95 depend on correct conformation and cannot be represented by simple
      "linear" peptides. By screening random peptide phage display libraries with
      polyclonal antibodies directed against conformation-dependant epitopes of EG95,
      we have selected a number of peptides that mimic these epitopes. The selected
      peptides did not show sequence homology to EG95. Antigen binding assays involving
      these peptides have provided evidence of at least four conformationally-dependant
      epitope regions on EG95. One of the selected peptides, E100, has been used to
      purify antibodies from anti-sera raised in sheep vaccinated with EG95. This
      yielded monospecific antibodies capable of recognizing recombinant EG95 in ELISA
      and native EG95 in Western blot assays. This antibody was demonstrated to be
      effective in antibody-dependant complement-mediated in vitro killing of
      Echinococcus granulosus oncospheres. Peptide E100 may represent the basis for a
      quality control assay for EG95 production, and has the potential to become a
      component of a synthetic peptide-based vaccine against E. granulosus.

PMID- 19095031
TI  - Construction and characterization of a novel DNA vaccine that is potent antigen
      specific tolerizing therapy for experimental arthritis by increasing
      CD4+CD25+Treg cells and inducing Th1 to Th2 shift in both cells and cytokines.
AB  - Currently available treatments for rheumatoid arthritis (RA) are often
      ineffective in ameliorating the progression of disease, particularly the invasive
      destruction of articular cartilage and bone, and RA remains incurable. Therefore,
      vaccinotherapy of RA with an antigen-specific tolerizing DNA vaccine may offer
      new promise for overcoming this difficulty. Using recombinant technology, the DNA
      sequences encoding chicken type II collagen (CCOL2A1) with deleted N-propeptides
      were obtained from the plasmid pPIC9K/pCalpha(1)(II), and then cloned into
      pcDNA3.1(+). The resulting recombinant plasmid pcDNA-CCOL2A1 was produced in
      Escherichia coli, purified, characterized and used as a tolerizing DNA vaccine
      for the treatment of collagen-induced arthritis (CIA). Therapeutic efficacy and
      potential action mechanisms of pcDNA-CCOL2A1 tolerizing DNA vaccine against CIA
      were studied. Here we demonstrate that a single intravenous treatment with novel
      tolerizing DNA vaccine pcDNA-CCOL2A1 can induce potent immune tolerance against
      CIA. The efficacy of this therapy was verified by clinical visual scoring,
      radiographic X-ray, histopathological examination, and anti-CII IgG levels.
      Furthermore, the action mechanism behind this efficacy can be at least partially
      attributed to increased CD4(+)CD25(+) T regulatory cells, which specifically down
      modulate the T lymphocyte proliferative response to CCII, induce a shift of Th1
      to Th2 cells, as well as down-regulate Th1-cytokine TNF-alpha, while up
      regulating both Th2-cytokine IL-10 and Th3-cytokine TGF-beta. More importantly,
      pcDNA-CCOL2A1 alone seems to be as effective as the current "golden standard"
      treatment, methotrexate (MTX). Taken together, these results suggest that we have
      successfully developed a novel tolerizing DNA vaccine encoding CCII, which is the
      first description of a tolerizing DNA vaccine encoding CCII for antigen-specific
      tolerizing therapy but not prophylactic against CIA.

PMID- 19095033
TI  - Booster vaccination of adults with reduced-antigen-content diphtheria, Tetanus
      and pertussis vaccine: immunogenicity 5 years post-vaccination.
AB  - At 60 months post-vaccination, adults (mean age 45.6 years) randomised to receive
      combined reduced-antigen-content diphtheria-tetanus and acellular pertussis
      vaccine (dTpa) versus tetanus-diphtheria (Td)+monovalent acellular pertussis (pa)
      were seroprotected against diphtheria (> or =0.016IU/mL Vero cell assay) and
      tetanus (> or =0.1IU/mL ELISA assay) in 94.4% and 96.2%, respectively (dTpa),
      compared with 93.7% and 90.6% (Td+pa). Anti-FHA, anti-PT and anti-PRN antibodies
      (> or =5EL.U/mL) were maintained in 100%, 89.5% and 95.0% of dTpa versus 100%,
      85.5% and 90.6% of pa vaccine recipients. At 5 years post boosting, antibody
      levels to diphtheria and tetanus are similar amongst adults receiving a dTpa or
      dT, and pertussis antibodies remain above pre-booster levels in at least 85%.

PMID- 19095034
TI  - Allergen databases and allergen semantics.
AB  - The efficacy of any specific bioinformatic analysis of the potential
      allergenicity of new food proteins depends directly on the nature and content of
      the databases that are used in the analysis. A number of different allergen
      related databases have been developed, each designed to meet a different need.
      These databases differ in content, organization, and accessibility. These
      differences create barriers for users and prevent data sharing and integration.
      The development and application of appropriate semantic web technologies, (for
      example, a food allergen ontology) could help to overcome these barriers and
      promote the development of more advanced analytic capabilities.

PMID- 19095032
TI  - Vaccination with HPV16 L2E6E7 fusion protein in GPI-0100 adjuvant elicits
      protective humoral and cell-mediated immunity.
AB  - A vaccine comprising human papillomavirus type 16 (HPV16) L2, E6 and E7 in a
      single tandem fusion protein (termed TA-CIN) has the potential advantages of both
      broad cross-protection against HPV transmission through induction of L2
      antibodies able to cross neutralize different HPV types and of therapy by
      stimulating T cell responses targeting HPV16 early proteins. However, patients
      vaccinated with TA-CIN alone develop weak HPV neutralizing antibody and E6/E7
      specific T cell responses. Here we test TA-CIN formulated along with the adjuvant
      GPI-0100, a semi-synthetic quillaja saponin analog that was developed to promote
      both humoral and cellular immune responses. Subcutaneous administration to mice
      of TA-CIN (20 microg) with 50microg GPI-0100, three times at biweekly intervals,
      elicited high titer HPV16 neutralizing serum antibody, robust neutralizing titers
      for other HPV16-related types, including HPV31 and HPV58, and neutralized to a
      lesser extent other genital mucosatropic papillomaviruses like HPV18, HPV45, HPV6
      and HPV11. Notably, vaccination with TA-CIN in GPI-0100 protected mice from
      cutaneous HPV16 challenge as effectively as HPV16 L1 VLP without adjuvant.
      Formulation of TA-CIN with GPI-0100 enhanced the production of E7-specific,
      interferon gamma producing CD8(+) T cell precursors by 20-fold. Vaccination with
      TA-CIN in GPI-0100 also completely prevented tumor growth after challenge with
      5x10(4) HPV16-transformed TC-1 tumor cells, whereas vaccination with TA-CIN alone
      delayed tumor growth. Furthermore, three monthly vaccinations with 125 microg of
      TA-CIN and 1000 microg GPI-0100 were well tolerated by pigtail macaques and
      induced both HPV16 E6/E7-specific T cell responses and serum antibodies that
      neutralized all HPV types tested.

PMID- 19095035
TI  - Age-related differential responses to curcumin-induced apoptosis during the
      initiation of colon cancer in rats.
AB  - Curcumin is a widely-used dietary supplement and a chemopreventive agent for
      various cancers. Pre-clinical chemopreventive studies rarely consider the effect
      of aging. We previously reported that unlike young animals, curcumin is
      ineffective in middle-aged rats for colon chemoprevention. This study
      investigated whether resistance to apoptosis during cancer initiation contributes
      to this age-dependent effect. Young, middle-aged, and old F344 rats were fed
      either curcumin (0.6%) or control diet. Colonic apoptosis was evaluated 0, 8, and
      16 h after azoxymethane (AOM) injection. Colonic Hsp70 mRNA levels, caspase-9
      activity, cell proliferation, and crypt morphology were measured. In AOM-treated
      rats, only middle-aged rats were resistant to curcumin-induced apoptosis whereas
      cell proliferation was reduced by curcumin in all ages. Curcumin-induced
      apoptosis was mediated by caspase-9 in young but not older rats. Transcriptional
      Hsp70 expression was induced in only young rats and was suppressed by curcumin.
      Therefore, the age-related difference in curcumin chemoprevention is due to a
      differential response in induction of apoptosis. The mitochondria-dependent
      pathway seems to mediate curcumin-induced apoptosis in young but not older
      animals. Hsp70 expression was not related with resistance to curcumin-induced
      apoptosis. Understanding age-related differences in the apoptotic response may
      lead to improved translation from pre-clinical animal studies to humans.

PMID- 19095036
TI  - Lack of genotoxic effect of food dyes amaranth, sunset yellow and tartrazine and
      their metabolites in the gut micronucleus assay in mice.
AB  - The food dyes amaranth, sunset yellow and tartrazine were administered twice, at
      24h intervals, by oral gavage to mice and assessed in the in vivo gut
      micronucleus test for genotoxic effects (frequency of micronucleated cells) and
      toxicity (apoptotic and mitotic cells). The concentrations of each compound and
      their main metabolites (sulfanilic acid and naphthionic acid) were measured in
      faeces during a 24-h period after single oral administrations of the food dyes to
      mice. Parent dye compounds and their main aromatic amine metabolites were
      detected in significant amounts in the environment of colonic cells. Acute oral
      exposure to food dye additives amaranth, sunset yellow and tartrazine did not
      induce genotoxic effect in the micronucleus gut assay in mice at doses up to 2000
      mg/kg b.w. Food dyes administration increased the mitotic cells at all dose
      levels when compared to controls. These results suggest that the transient DNA
      damages previously observed in the colon of mice treated by amaranth and
      tartrazine by the in vivo comet assay [Sasaki, Y.F., Kawaguchi, S., Kamaya, A.,
      Ohshita, M., Kabasawa, K., Iwama, K., Taniguchi, K., Tsuda, S., 2002. The comet
      assay with 8 mouse organs: results with 39 currently used food additives. Mutat.
      Res. 519, 103-119] are unable to be fixed in stable genotoxic lesions and might
      be partly explained by local cytotoxicity of the dyes.

PMID- 19095037
TI  - Anti-inflammatory effects of essential oil isolated from the buds of Cleistocalyx
      operculatus (Roxb.) Merr and Perry.
AB  - Cleistocalyx operculatus (Roxb.) Merr and Perry buds (Myrtaceae) are widely used
      in folk medicine for the treatment of gastric ailments as well as an antiseptic
      agent in China, Vietnam and some other tropical countries. However, to be
      clinically useful, more scientific data are needed. In the present study, we
      investigated the in vitro and in vivo anti-inflammatory activities of the
      essential oil of the C. operculatus buds (EO-CO). In the applied tests, EO-CO
      significantly inhibited lipopolysaccharide (LPS)-induced secretion of pro
      inflammatory cytokines, including tumor necrosis factor-alpha (TNF-alpha) and
      interleukin-1beta (IL-1beta), in RAW 264.7 cells, a mouse macrophage-like cell
      line. Also the mRNA expression of TNF-alpha and IL-1beta was suppressed by
      treatment with EO-CO in LPS-stimulated RAW 264.7 cells. Moreover, reporter gene
      analysis revealed that the EO-CO significantly blocked LPS-induced
      transcriptional activation of NF-kappaB in RAW 264.7 cells. Nuclear translocation
      of p65 subunit was also suppressed by EO-CO treatment. In addition, EO-CO
      inhibited phorbol ester-induced increase in ear swelling and skin water content
      in BALB/c mice. These results suggest that EO-CO might exert an anti-inflammatory
      effect by suppressing the expression of pro-inflammatory cytokines which is
      mediated, at least in part, by blocking NF-kappaB activation.

PMID- 19095038
TI  - Structural characterization of promoter sequences of the gene coding human PKI55
      protein, a protein kinase C inhibitor.
AB  - The PKI55 protein was identified in our laboratory as specific protein kinase C
      inhibitor. We previously demonstrated that PKI55 is poorly translated in vivo and
      acts promoting PKC degradation and establishing a feedback loop of inhibition.
      However, our understanding of mechanisms by which the expression of PKI55 is
      regulated, is limited. In the present work we investigated the mRNA expression of
      PKI55 in human tissues by Northern blotting and RT-PCR, demonstrating that it is
      highly expressed in brain tissue. Moreover, since the computational analysis of
      the gene promoter region showed two sites (Box 1 and Box 2) similar to consensus
      sequences for AP1 and GAGA factors, we investigated their ability to bind to
      these proteins. Electrophoretic mobility shift assays showed that GAGA factors
      preferentially interacted with Box 2, while AP1 elements linked preferentially
      Box 1 sequence. We suggest that the interaction of these transcription factors
      with Box 1 and Box 2 could regulate the transcription of the PKI55 gene and,
      consequently, the expression of PKC.

PMID- 19095039
TI  - Evolution of cooperation on dynamical graphs.
AB  - There are two key characteristic of animal and human societies: (1) degree
      heterogeneity, meaning that not all individual have the same number of
      associates; and (2) the interaction topology is not static, i.e. either
      individuals interact with different set of individuals at different times of
      their life, or at least they have different associations than their parents.
      Earlier works have shown that population structure is one of the mechanisms
      promoting cooperation. However, most studies had assumed that the interaction
      network can be described by a regular graph (homogeneous degree distribution).
      Recently there are an increasing number of studies employing degree heterogeneous
      graphs to model interaction topology. But mostly the interaction topology was
      assumed to be static. Here we investigate the fixation probability of the
      cooperator strategy in the prisoner's dilemma, when interaction network is a
      random regular graph, a random graph or a scale-free graph and the interaction
      network is allowed to change. We show that the fixation probability of the
      cooperator strategy is lower when the interaction topology is described by a
      dynamical graph compared to a static graph. Even a limited network dynamics
      significantly decreases the fixation probability of cooperation, an effect that
      is mitigated stronger by degree heterogeneous networks topology than by a degree
      homogeneous one. We have also found that from the considered graph topologies the
      decrease of fixation probabilities due to graph dynamics is the lowest on scale
      free graphs.

PMID- 19095040
TI  - The C-type lectin CD209b is expressed on microglia and it mediates the uptake of
      capsular polysaccharides of Streptococcus pneumoniae.
AB  - Although Streptococcus pneumoniae is the major cause of meningitis, how it causes
      disease is poorly understood. The C-type lectin SIGN-R1 mediates the recently
      described SIGN-R1 complement activation pathway, which operates against capsular
      polysaccharides (CPSs) of S. pneumoniae in splenic marginal macrophages. Here, we
      demonstrate that SIGN-R1, as well as the rat SIGN-R1 homologue CD209b are
      expressed in most regions of mouse or rat brain, respectively. Moreover, both C
      type lectins are obviously expressed on microglia, but not on neurons or
      astrocytes. We also found that rat CD209b mediates the uptake of dextran or CPS14
      within the rat splenic marginal zone, similar to SIGN-R1. On microglia, rat
      CD209b also mediates the uptake of CPS14 of S. pneumoniae. Our findings strongly
      suggest that both rat CD209b and SIGN-R1 on microglia mediate the SIGN-R1
      complement activation pathway against S. pneumoniae, and thereby plays an
      important role in the pathogenesis of pneumococcal meningitis.

PMID- 19095041
TI  - Dietary tryptophan restriction in rats triggers astrocyte cytoskeletal
      hypertrophy in hippocampus and amygdala.
AB  - We have previously reported that dietary tryptophan (TRP) restriction in a rat
      crucial postnatal developmental stage induces depression-like behavior and alters
      dendritic spine density in CA1 pyramidal neurons and granule cells of the
      hippocampus. Due to astrocyte involvement in critical brain mechanisms, it seems
      worth to investigate possible adaptive changes in the glial population with TRP
      restriction. Experimental rats were fed with low TRP diet (20% of TRP level of
      the laboratory rat chow) from postnatal days 30-60. Antibody against glial
      fibrillary acidic protein (GFAP), a principal intermediate filament in
      astrocytes, was used to evaluate cytoskeletal hypertrophy and glial
      proliferation. Our results showed an increase in size and branching of GFAP
      immunoreactive (IR) cells in the dorsal hippocampus and amygdala, characteristics
      of an astrocytic activation. No significant differences were found regarding the
      number of GFAP-IR cells in both regions. These results indicate that dietary TRP
      restriction can induce astrocytic activation, hence, provide further evidences
      supporting the hypothesis that serotonin may also modulate glial morphology.

PMID- 19095042
TI  - Silencing of ZnT1 reduces Zn2+ efflux in cultured cortical neurons.
AB  - Zinc dyshomeostasis in brain might be involved in the pathogenesis of a series of
      brain diseases such as Alzheimer's disease and stroke. It is essential that the
      level of intracellular free Zn2+ in neurons is tightly controlled to maintain a
      narrow window of optimal concentration. The plasma membrane bound transporter
      ZnT1 is suggested to lower intracellular Zn2+ concentration. In this study, the
      function of ZnT1 in cultured cortical neurons was studied. Using vector-based
      shRNA interference, the expression of this protein was reduced approximately 40%
      in cultured rat cortical neurons when measured by immunofluorescence using a ZnT1
      antibody. Changes in intracellular Zn2+ levels were tracked in individual neurons
      by microfluorometry using the Zn2+ selective fluorophore, FluoZin3. Unopposed
      Zn2+ efflux was measured by first loading cultured cortical neurons with Zn2+
      then reducing extracellular Zn2+ to near zero by addition of EDTA. Reducing ZnT1
      expression caused Zn2+ efflux to decrease compared with the Zn2+ efflux measured
      in nonsense transfected neurons, suggesting that ZnT1 plays a direct role in Zn2+
      efflux. ZnT1 dependent Zn2+ efflux rate was higher in the first 10 min than at
      later time periods suggesting that ZnT1-mediated efflux was heavily dependent on
      the intracellular free Zn2+ concentration and/or required an outwardly directed
      Zn2+ gradient.

PMID- 19095044
TI  - Sex differences in water maze performance and cortical neurotrophin levels of
      LHX7 null mutant mice.
AB  - Mice lacking both alleles of the LIM-homeobox gene Lhx7 display dramatically
      reduced number of forebrain cholinergic neurons. Given the fact that sex
      differences are consistently observed in forebrain cholinergic function, in the
      present study we investigated whether the absence of LHX7 differentially affects
      water maze performance in the two sexes. Herein we demonstrate that LHX7 null
      mutants display a sex-dependent impairment in water maze, with females appearing
      more affected than males. Moreover, neurotrophin assessment revealed a
      compensatory increase of brain-derived neurotrophic factor and neurotrophin 3 in
      the neocortex of both male and female mutants and an increase of nerve growth
      factor levels only in the females. Nevertheless, the compensatory increase of
      cortical neurotrophin levels did not restore cognitive abilities of Lhx7
      homozygous mutants. Finally, our analysis revealed that cortical neurotrophin
      levels correlate negatively with water maze proficiency, indicating that there is
      an optimal neurotrophin level for successful cognitive performance.

PMID- 19095043
TI  - Extra-nuclear estrogen receptor GPR30 regulates serotonin function in rat
      hypothalamus.
AB  - Selective serotonin reuptake inhibitors (SSRIs), such as Prozac, are used to
      treat mood disorders. SSRIs attenuate (i.e. desensitize) serotonin 1A (5-HT(1A))
      receptor signaling, as demonstrated in rats through decreased release of oxytocin
      and adrenocorticotropin hormone (ACTH) following 5-HT(1A) receptor stimulation.
      Maximal therapeutic effects of SSRIs for treatment of mood disorders, as well as
      effects on hypothalamic 5-HT(1A) receptor signaling in animals, take 1 to 2 weeks
      to develop. Estradiol also attenuates 5-HT(1A) receptor signaling, but, in rats,
      these effects occur within 2 days; thus, estrogens or selective estrogen receptor
      modulators may serve as useful short-term tools to accelerate desensitization of
      5-HT(1A) receptors in response to SSRIs if candidate estrogen receptor targets in
      the hypothalamus are identified. We found high levels of GPR30, which has been
      identified recently as a pertussis-toxin (PTX) sensitive G-protein-coupled
      estrogen receptor, in the hypothalamic paraventricular nucleus (PVN) of rats.
      Double-label immunohistochemistry revealed that GPR30 co-localizes with 5-HT(1A)
      receptors, corticotrophin releasing factor (CRF) and oxytocin in neurons in the
      PVN. Pretreatment with PTX to the PVN before peripheral injections of 17-beta
      estradiol 3-benzoate completely prevented the reduction of the oxytocin response
      to the 5-HT(1A) receptor agonist, (+)-8-hydroxy-2-dipropylaminotetralin (DPAT).
      Treatment with the selective GRP30 agonist, G-1, attenuated 5-HT(1A) receptor
      signaling in the PVN as measured by an attenuated oxytocin (by 29%) and ACTH (by
      31%) response to DPAT. This study indicates that a putative extra-nuclear
      estrogen receptor, GPR30, may play a role in estradiol-mediated attenuation of 5
      HT(1A) receptor signaling, and potentially in accelerating the effects of SSRIs
      in treatment of mood disorders.

PMID- 19095045
TI  - The muscarinic inhibition of the potassium M-current modulates the action
      potential discharge in the vestibular primary-afferent neurons of the rat.
AB  - There is consensus that muscarinic and nicotinic receptors expressed in
      vestibular hair cells and afferent neurons are involved in the efferent
      modulation of the electrical activity of the afferent neurons. However the
      underlying mechanisms of postsynaptic control in neurons are not well understood.
      In our work we show that the activation of muscarinic receptors in the vestibular
      neurons modulates the potassium M-current modifying the activity of afferent
      neurons. Whole-cell patch-clamp recordings were made on vestibular-afferent
      neurons isolated from Wistar rats (postnatal days 7-10) and held in primary
      culture (18-24 h). The M-current was studied during its deactivation after
      depolarizing voltage-clamp pulses. In 68% of the cells studied, those of larger
      capacitance, the M-current antagonists linopirdine and XE-991 reduced the
      amplitude of the M-current by 54%+/-7% and 50%+/-3%. The muscarinic-receptor
      agonist oxotremorine-M also significantly reduced the M-current by 58%+/-12% in
      the cells. The action of oxotremorine-M was blocked by atropine, thus indicating
      its cholinergic nature. The erg-channel blocker E-4031 did not significantly
      modify the M-current amplitude. In current-clamp experiments, linopirdine, XE
      991, and oxotremorine-M modified the discharge response to current pulses from
      single spike to multiple spiking, reducing the adaptation of the electrical
      discharge. Our results indicate that large soma-size cultured vestibular-afferent
      neurons (most probably calyx-bearing neurons) express the M-current and that the
      modulation of this current by activation of muscarinic-receptor reduces its spike
      frequency adaptation.

PMID- 19095046
TI  - Intermittent hypoxia regulates RNA polymerase II in hippocampus and prefrontal
      cortex.
AB  - Intermittent hypoxia (IH) is a major pathological factor in the development of
      neural deficits associated with sleep-disordered breathing. Here we demonstrate
      that IH lasting 2 or 30 days, but not sustained hypoxia (SH) of the same
      duration, was accompanied by several posttranslational modifications of the large
      subunit of RNA polymerase II, Rpb1, including hydroxylation of proline 1465,
      phosphorylation of serine 5 residues within the C-terminal domain, and
      nondegradative ubiquitylation. These modifications were found to occur in two
      regions of the brain, hippocampal region CA1 and the prefrontal cortex, but not
      in neocortex, brainstem and CA3 region of hippocampus. We also found that mice
      exposed to 14 or 30 days of IH, but not SH, demonstrated cognitive deficits in
      behavioral assays. Furthermore, by using the pheochromocytoma-derived PC12 cell
      line, we showed that, under in vitro IH conditions, induction of Rpb1
      hydroxylation, phosphorylation, and ubiquitylation required that the von Hippel
      Lindau protein be present. We hypothesize that the observed modifications of Rpb1
      participate in regulating the expression of genes involved in mediating cognitive
      deficits evoked by chronic IH.

PMID- 19095048
TI  - Characterization of the murine Dfna5 promoter and regulatory regions.
AB  - Mutations in DFNA5 cause a non-syndromic autosomal dominant type of hearing loss.
      Although not much is known regarding the physiological function of DFNA5, it is
      not only related to hearing loss. A clear link with cancer exists. For example,
      methylation of the 5' flanking region of DFNA5 was detected in breast, colorectal
      and gastric cancer. So far, this 5' flanking region has not been studied in
      detail. Here, we describe the identification of the cochlear transcription
      initiation site (TIS), the identification of the core promoter region between 
      120 and +70 relative to the TIS and the identification of an enhancer (between 
      121 and -356 bp) and a silencer element (between -356 and -670 bp). Results were
      similar in HEK293 cells and in the organ of Corti cell line OC-k3. Transfection
      with a reversely-oriented construct resulted in high transcriptional activity. We
      subsequently confirmed this antisense activity and identified a novel antisense
      transcript partly overlapping Dfna5.

PMID- 19095047
TI  - Expression of nicotinic acetylcholine receptors and subunit messenger RNAs in the
      enteric nervous system of the neonatal rat.
AB  - In the enteric nervous system (ENS) excitatory nicotinic cholinergic transmission
      is mediated by neuronal nicotinic acetylcholine receptors (nAChR) and is critical
      for the regulation of gastric motility. nAChRs are ligand-gated pentameric ion
      channels found in the CNS and peripheral nervous system. The expression of
      heteromeric nAChR and receptor subunit mRNAs was investigated in the neonatal rat
      ENS using receptor autoradiography with the radiolabeled ligand (125)I
      epibatidine, and in situ hybridization with subtype specific probes for ligand
      binding alpha (alpha2, alpha3, alpha4, alpha5, alpha6) and structural beta
      (beta2, beta3, beta4) subunits. The results showed strong nicotine sensitive
      binding of (125)I-epibatidine around the stomach, and small and large intestines.
      The binding was partially displaced by A85380, a nicotinic ligand which
      differentiates between different heteromeric nAChR subtypes, suggesting a mixed
      receptor population. Radioactive in situ hybridization detected expression of
      alpha3, alpha5, alpha7, beta2 and beta4 mRNA in the myenteric plexus of the
      stomach, and small and large intestines. In the submucosal plexus of the small
      and large intestines expression of alpha3, alpha5 and beta4 was found in some
      ganglia. There was no signal for alpha4, alpha6 and beta3 in the ENS but positive
      hybridization signal for alpha2 transcripts was seen in some areas of the small
      intestines. However, the signal was not associated with any ganglion cells. The
      results confirm the presence of heteromeric nAChRs in the ENS similar to those
      found in the peripheral nervous system, with the majority being composed of
      alpha3(alpha5)beta4, and a few alpha3beta2 nAChRs. In addition, homomeric alpha7
      nAChRs could be present.

PMID- 19095049
TI  - Developmentally dynamic changes of DNA methylation in the mouse Snurf/Snrpn gene.
AB  - The mouse Snurf/Snrpn gene has two differentially methylated regions (DMRs), the
      maternally methylated region at the 5' end (DMR1) and the paternally methylated
      region at the 3' end (DMR2). DMR1, a region that includes the Snrpn promoter and
      the entire intron 1, has been thought to be a germline DMR, which inherits the
      parental-specific methylation profile from the gametes. DMR1 is not only
      associated with imprinted Snrpn expression, but implicated in imprinting control
      of other genes in the region. We have now characterized the highly conserved
      activator sequence (CAS) in the Snrpn intron 1 among human and rodents and
      demonstrate that the mouse CAS is not a germline DMR but shows developmentally
      dynamic changes of DNA methylation and has methylation-sensitive enhancer
      activity. The tissue-specific methylation of the mouse CAS and its methylation
      sensitive enhancer activity may control tissue-specific expression of IC
      transcripts, resulting in the establishment and/or maintenance of imprinting in
      the Snrpn locus.

PMID- 19095050
TI  - EGF-recruited JunD/c-fos complexes activate CD2AP gene promoter and suppress
      apoptosis in renal tubular epithelial cells.
AB  - CD2-associated protein (CD2AP) plays a critical role in the maintenance of the
      kidney filtration barrier. In this study, we showed that epidermal growth factor
      (EGF) led to an increase of the CD2AP protein and mRNA in the human renal
      proximal tubular epithelial cell line HK-2 cells, which was due to the elevation
      of CD2AP promoter activity. Upon deletion and mutation analysis, electrophoretic
      mobility shift assays and chromatin immunoprecipitation, an AP-1-like element
      within CD2AP promoter was characterized, by which EGF recruited c-fos and JunD,
      two components of AP-1, to the human CD2AP gene promoter and suppressed
      angiotensin II-induced apoptosis in HK-2 cells. Specific siRNA was synthesized to
      knock down the human CD2AP gene in HK-2 cells. We found that CD2AP deficiency
      attenuated the inhibitory effects of EGF and predisposed the renal tubular
      epithelial cells to undergo angiotensin II-induced apoptosis. Furthermore, EGF
      induced increases of CD2AP protein and mRNA expressions in HK-2 cells were
      significantly inhibited by the transfection of dominant negative JunD or c-fos
      vector, which was in parallel with a marked reduction of antiapoptotic effect of
      EGF. These results indicated that the antiapoptotic effect of EGF/CD2AP signal
      transduction was mediated by JunD and c-fos, at least partially. This study
      defined a new EGF/AP-1/CD2AP mediated cell-survival signaling, which might be
      useful to clarify the molecular mechanisms responsible for CD2AP associated
      kidney diseases.

PMID- 19095051
TI  - DNA single- and double-strand breaks by alkaline- and immuno-comet assay in
      lymphocytes of workers exposed to styrene.
AB  - Occupational exposure to styrene was studied in 34 workers employed in the
      production of fiberglass-reinforced plastic sheets and compared to 29 unexposed
      healthy controls. We evaluated genotoxic effects induced by occupational styrene
      exposure in lymphocytes by alkaline version of the comet assay to detect single
      strand breaks (SSBs), DNA oxidation products (formamido pyrimidine glycosilase
      (Fpg)- and endonuclease (Endo III)-sensitive sites) and DNA repair kinetics
      studies, as well as the neutral version of comet assay for DNA double-strand
      breaks (DSBs). An innovative aspect of this study was the use of immuno-comet
      assay, a new technique that recognizes DSBs with specific antibody by DAPI/FITC
      method. The battery of parameters included markers of external and internal
      exposure. Exposed workers showed significant high levels of SSBs (p<0.0001) and
      DSBs (p<0.0001) in neutral- and immuno-comet assay. A drastic decrease in DNA
      repair activity as compared to controls was observed (180 min vs. 35 min).
      Styrene workplace concentration significantly correlated with alkaline comet
      parameters (TM, p=0.013; TI, p=0.008), in negative with TL (p=0.022), and with
      DNA-base oxidation (TM Endo III, p=0.048 and TI Endo III, p=0.028). There was a
      significant negative correlation between urinary metabolites (MA+PGA) and TM Endo
      III (p=0.032) and TI Endo III (p=0.017).

PMID- 19095052
TI  - Cytotoxicity and gene expression profiling of two hydroxylated polybrominated
      diphenyl ethers in human H295R adrenocortical carcinoma cells.
AB  - Polybrominated diphenyl ethers (PBDEs) are commonly used as flame retardants in a
      variety of commercial and household products. They have been detected in the
      environment and accumulate in mammalian tissues and fluids. PBDE toxicity is
      thought to be associated with endocrine disruption, developmental neurotoxicity
      and changes in fetal development. Although humans are exposed to PBDEs, our
      knowledge of the effects of PBDE metabolites on human cells with respect to
      health risk is insufficient. Two hydroxylated PBDEs (OH-PBDEs), 2-OH-BDE47 and 2
      OH-BDE85, were investigated for their effects on cell viability/proliferation,
      DNA damage, cell cycle distribution and gene expression profiling in H295R
      adrenocortical carcinoma cells. We show that the two agents are cytotoxic in a
      dose-dependent manner only at micromolar concentrations, with 2-OH-BDE85 being
      more toxic than 2-OH-BDE47. However, no DNA damage was observed for either
      chemical, suggesting that the biological effects of OH-PBDEs occur primarily via
      non-genotoxic routes. Furthermore, no evidence of aryl hydrocarbon receptor (AHR)
      mediated, dioxin-like toxicity was observed. Instead, we report that a micromolar
      concentration of OH-PBDEs induces transcriptional changes associated with
      endoplasmic reticulum stress and the unfolded protein response. We discuss
      whether OH-PBDE bioaccumulation could result in impairment of the adrenocortical
      secretory function.

PMID- 19095053
TI  - Estrogen and hearing from a clinical point of view; characteristics of auditory
      function in women with Turner syndrome.
AB  - Turner syndrome is a chromosomal aberration affecting 1:2000 newborn girls, in
      which all or part of one X chromosome is absent. This leads to ovarial dysgenesis
      and little or no endogenous estrogen production. These women have, among many
      other syndromal features, a high occurrence of ear and hearing problems, and
      neurocognitive dysfunctions, including reduced visual-spatial abilities; it is
      assumed that estrogen deficiency is at least partially responsible for these
      problems. In this, study 30 Turner women aged 40-67, with mild to moderate
      hearing loss, performed a battery of hearing tests aimed at localizing the lesion
      causing the sensorineural hearing impairment and assessing central auditory
      function, primarily sound localization. The results of TEOAE, ABR and speech
      recognition scores in noise were all indicative of cochlear dysfunction as the
      cause of the sensorineural impairment. Phase audiometry, a test for sound
      localization, showed mild disturbances in the Turner women compared to the
      reference group, suggesting that auditory-spatial dysfunction is another facet of
      the recognized neurocognitive phenotype in Turner women.

PMID- 19095054
TI  - Pharmacological properties of the extract and some isolated compounds of Clausena
      lansium stem bark: anti-trichomonal, antidiabetic, anti-inflammatory,
      hepatoprotective and antioxidant effects.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: Clausena lansium (Fool's Curry Leaf) is used for
      various ethnomedical conditions in some countries, including bronchitis, malaria,
      viral hepatitis, acute and chronic gastro-intestinal inflammation, and as a spicy
      substitute of the popular Curry leaf tree (Murraya koenigii). AIM OF THE STUDY:
      This study was to evaluate the ethnomedical uses of the stem bark in inflammatory
      conditions, hepatotoxicity and to determine the anti-diabetic and anti
      trichomonal properties of the plant. MATERIALS AND METHOD: Anti-trichomonal, in
      vivo and in vitro antidiabetic and insulin stimulating, anti-inflammatory,
      hepatoprotective and anti-oxidant activities using Trichomonas gallinae, glucose
      loaded rats and in vitro insulin secreting cell line (INS-1 cell), carrageenin
      induced rat paw oedema, CCl(4)-induced hepatotoxicity and DPPH scavenging ability
      methods respectively for the extracts and some isolates were determined. RESULTS:
      A dichloromethane extract was superior over methanolic extract with respect to an
      anti-trichomonal activity which was measured after 24 and 48 h. The isolated
      compounds imperatorin and 3-formylcarbazole had the main anti-trichomonal
      activity (LC(50)s of 6.0, 3.0 and 3.6, 9.7 microg/mL after 24 and 48 h,
      respectively). Methanolic extract (100 mg/kg) induced maximum and significant
      (p<0.05) anti-hyperglycaemic activity of 15.8% at 30 min and a 38.5% increase in
      plasma insulin at 60 min, compared to control. The increase in plasma insulin
      after 60 min, compared to 0 min, was 62.0% (p<0.05). The significant 174.6%
      increase of insulin release from INS-1 cells (in vitro) at 0.1 mg/ml indicates
      that it mediates its antidiabetic action mainly by stimulating insulin release.
      Imperatorin and chalepin were the major active constituents increasing in vitro
      insulin release to 170.3 and 137.9%, respectively. 100 mg/kg of the methanolic
      extract produced an anti-inflammatory activity after 4 h. A sedative effect was
      not observed. 100 and 200 mg/kg of methanolic extract administered i.p., reduced
      CCl4-induced hepatotoxicity firstly by 5.3 and 8.4% reduction in phenobarbitone
      sleeping time respectively, secondly by reversing the reduction in serum liver
      proteins by 7.0-8.8%, serum AST, ALT and ALP activities by 27.7-107.9% and
      thirdly by diminishing increased values of plasma AST, ALT and ALP activities by
      13.2-83.8%. The extract exhibited antioxidant activities. CONCLUSION: The
      hepatoprotective activity of C. lansium is partly due to its anti-oxidant and
      anti-inflammatory properties and confirms its folkloric use in the treatment of
      gastro-intestinal inflammation, bronchitis and hepatitis. In addition the use of
      C. lansium stem bark would be useful in diabetes and trichomoniasis.

PMID- 19095055
TI  - Histone-like protein H-NS regulates biofilm formation and virulence of
      Actinobacillus pleuropneumoniae.
AB  - Actinobacillus pleuropneumoniae is the causative agent of porcine contagious
      pleuropneumonia, a very important swine respiratory infectious disease causing
      great economic losses worldwide. The pathogenesis of this disease is still not
      completely understood. Biofilm formation contributes to full virulence in many
      Gram-negative bacterial pathogens. In the present study, two biofilm-producing
      mutants were identified from the transposon mutagenesis mutant pools of A.
      pleuropneumoniae strain 4074 of serovar 1 (a non-biofilm forming strain). Inverse
      PCR and sequencing analysis revealed that the hns gene encoding the histone-like
      nucleoid structuring protein (H-NS) was inactivated by the mini-Tn10 transposon
      in both mutant strains. Further analysis revealed that the virulence was
      attenuated in the mutant strains when their haemolytic activity and 50% lethal
      doses in mice were compared with the parental strain. Real-time RT-PCR analysis
      suggested that the down-regulation of the exotoxin genes in the hns mutants may
      partly contribute to the virulence attenuation. Our data indicate that H-NS plays
      important roles in regulating biofilm formation and virulence in A.
      pleuropneumoniae.

PMID- 19095056
TI  - Protocatechuic acid promotes cell proliferation and reduces basal apoptosis in
      cultured neural stem cells.
AB  - Protocatechuic acid (PCA), a phenolic compound isolated from the kernels of
      Alpinia oxyphylla, showed anti-oxidant neuroprotective property in our previous
      study. However, it is still unknown whether PCA have effects on the cultured
      neural stem cells (NSCs). In this study, we investigated the roles of PCA in the
      survival and apoptosis of rat NSCs under normal conditions. NSCs obtained from
      13.5-day-old rat embryos were propagated as neurospheres and cultured under
      normal conditions with or without PCA for 4 and 7 days. The cell viability was
      determined by the cell counting kit-8 (CCK-8) test, while cell proliferation was
      assayed by bromodeoxyuridine (BrdU) labeling. PCA increased the cellular
      viability of NSCs and stimulated cell proliferation in a dose- and time-dependent
      manner. Apoptotic cells were detected after 4 days by observing the nuclear
      morphological changes and flow cytometric analysis. Compared with the control on
      both culture days, treatment with PCA effectively reduced the levels of apoptosis
      of NSCs. At the same time, the reactive oxygen species (ROS) level in NSCs was
      depressed. In addition, PCA also significantly decreased the activity of elevated
      caspase-3, indicating that PCA may inhibit apoptosis of NSCs via suppression of
      the caspase cascade. These results suggest that PCA may be a potential growth
      inducer and apoptosis inhibitor for NSCs.

PMID- 19095057
TI  - Effects of perfluorooctanoic acid on mouse mammary gland development and
      differentiation resulting from cross-foster and restricted gestational exposures.
AB  - The adverse consequences of developmental exposures to perfluorooctanoic acid
      (PFOA) are established in mice, and include impaired development of the mammary
      gland (MG). However, the relationships between timing or route of exposure, and
      consequences in the MG have not been characterized. To address the effects of
      these variables on the onset and persistence of MG effects in female offspring,
      timed pregnant CD-1 dams received PFOA by oral gavage over various gestational
      durations. Cross-fostering studies identified the 5mg/kg dose, under either
      lactational- or intrauterine-only exposures, to delay MG development as early as
      postnatal day (PND) 1, persisting beyond PND 63. Intrauterine exposure during the
      final days of pregnancy caused adverse MG developmental effects similar to that
      of extended gestational exposures. These studies confirm a window of MG
      sensitivity in late fetal and early neonatal life, and demonstrate developmental
      PFOA exposure results in early and persistent MG effects, suggesting permanent
      consequences.

PMID- 19095058
TI  - Stereological investigation and expression of calcium-binding proteins in
      developing human inferior colliculus.
AB  - The mammalian inferior colliculus (IC) is a major relay nucleus in the auditory
      pathway. Prenatal development of the human IC has been inadequately studied. The
      present study reports the morphometric development and maturation of the human IC
      using unbiased stereology, in 18 aborted fetuses of various gestational ages (12
      29 weeks) and two babies aged 40 postnatal days (PND) and 5 months (that died of
      postoperative complications). It also demonstrates the functional maturation of
      the IC by examining the expression of calcium-binding proteins--parvalbumin (PV)
      and calbindin (CB). There was a significant increase in the total number of
      neurons and glia from 18 weeks of gestation (WG). The glia and neuron volume
      increased significantly from 16 WG to 22 WG, respectively. The total volume of IC
      also increased significantly from 18 WG onwards. On the other hand, the number
      and volume of undifferentiated cell bodies across all ages decreased
      significantly. Expression of CB was concentrated in the dorsal cortex while that
      of PV was mainly confined to the central nucleus of the IC, possibly indicating
      an early segregation of parallel processing of information in the auditory
      pathways. Intense staining for CB in the soma and dendrites appeared earlier than
      that of the PV. The morphological maturation appeared to overlap the onset of
      functional maturation suggesting an activity-dependent mechanism in the
      development of IC.

PMID- 19095059
TI  - Regulation of progesterone receptor isoforms content in human astrocytoma cell
      lines.
AB  - Progesterone regulates several functions through the interaction with its
      intracellular receptor (PR) which expresses two isoforms with different functions
      and regulation: PR-A and PR-B. Both PR isoforms have been detected in human
      astrocytomas, the most common and aggressive primary brain tumours, but their
      regulation and function are unknown. We studied the effects of estradiol,
      progesterone and their receptor antagonists (ICI 182,780 and RU 486) on PR
      isoforms content in U373 and D54 human astrocytoma cell lines, respectively
      derived from grades III and IV astrocytomas, by Western blot analysis. In U373
      cells we also evaluated the effects of PR-A overexpression on cell growth. We
      observed that in U373 cells estradiol increased the content of both PR isoforms
      whereas in D54 cells it had no effects. Estradiol effects were blocked by ICI
      182,780. In both cell lines, PR isoforms content was down-regulated by
      progesterone after estradiol treatment. This effect was blocked by RU 486. We
      observed that overexpression of PR-A significantly diminished the increase in
      U373 cells number produced after progesterone treatment. Our results suggest a
      differential PR isoforms regulation depending on the evolution grade of human
      astrocytoma cells, and an inhibitory role of PR-A on progesterone effects on
      astrocytomas cell growth.

PMID- 19095060
TI  - Validation of the mechanism of cholesterol binding by StAR using short molecular
      dynamics simulations.
AB  - We previously proposed an original two-state cholesterol binding mechanism by
      StAR, in which the C-terminal alpha-helix of StAR gates the access of cholesterol
      to its binding site cavity. This cavity, which can accommodate one cholesterol
      molecule, was proposed to promote the reversible unfolding of the C-terminal
      alpha-helix and allow for the entry and dissociation of cholesterol. In our
      molecular model of the cholesterol-StAR complex, the hydrophobic moiety of
      cholesterol interacts with hydrophobic amino acid side-chains located in the C
      terminal alpha-helix and at the bottom of the cavity. In this study, we present a
      structural in silico analysis of StAR. Molecular dynamics simulations showed that
      point mutations of Phe(267), Leu(271) or Leu(275) at the alpha-helix 4 increased
      the gyration radius (more flexibility) of the protein's structure, whereas the
      salt bridge double mutant E169M/R188M showed a decrease in flexibility (more
      compactness). Also, in the latter case, an interaction between Met(169) and
      Phe(267) disrupted the hydrophobic cavity, rendering it impervious to ligand
      binding. These obtained results are in agreement with previous in vitro
      experiments, and provide further validation of the two-state binding mode of
      action.

PMID- 19095061
TI  - Short alleles of both GGN and CAG repeats at the exon-1 of the androgen receptor
      gene are associated to increased PSA staining and a higher Gleason score in human
      prostatic cancer.
AB  - The exon 1 of the human androgen receptor (AR) gene contains two length
      polymorphisms of CAG (polyglutamine) and GGN (polyglycine). "In vitro"
      experiments suggest that the larger GGN repeats provide a lower AR-protein yield,
      whereas the larger CAG repeats decrease the AR transcriptional activity, both
      decreasing the AR signalling intensity. Here we have tested such possibilities in
      human prostatic cancer (CaP) specimens. We used 72 archival samples of radical
      prostatectomy. Parallel slides were used for AR protein or PSA
      immunohistochemistry, and for genotyping studies. Polymorphisms were genotyped by
      PCR, fragment length analysis and sequencing selected samples. The AR staining
      was positively correlated with the Gleason score (r=0.320; P=0.005), but it was
      not correlated to CAG or GGN repeat length or PSA staining. The number of GGN
      repeats was negatively correlated to the intensity of PSA staining (r=-0.243;
      P=0.04). Combination of short alleles of both tracts was significantly higher in:
      the heavier stained tertiles for PSA (P=0.03) and AR (P=0.06); and in the
      subgroup of samples having a Gleason score of 7 or higher (P=0.021). The results
      support the hypothesis that the shorter alleles of CAG and GGN repeats in the AR
      gene are associated to an increased AR signalling intensity in human prostate
      cancer, and with more aggressive forms of the disease.

PMID- 19095062
TI  - Inhibition of human catechol-O-methyltransferase (COMT)-mediated O-methylation of
      catechol estrogens by major polyphenolic components present in coffee.
AB  - In the present study, we investigated the inhibitory effect of three catechol
      containing coffee polyphenols, chlorogenic acid, caffeic acid and caffeic acid
      phenethyl ester (CAPE), on the O-methylation of 2- and 4-hydroxyestradiol (2-OH
      E(2) and 4-OH-E(2), respectively) catalyzed by the cytosolic catechol-O
      methyltransferase (COMT) isolated from human liver and placenta. When human liver
      COMT was used as the enzyme, chlorogenic acid and caffeic acid each inhibited the
      O-methylation of 2-OH-E(2) in a concentration-dependent manner, with IC(50)
      values of 1.3-1.4 and 6.3-12.5 microM, respectively, and they also inhibited the
      O-methylation of 4-OH-E(2), with IC(50) values of 0.7-0.8 and 1.3-3.1 microM,
      respectively. Similar inhibition pattern was seen with human placental COMT
      preparation. CAPE had a comparable effect as caffeic acid for inhibiting the O
      methylation of 2-OH-E(2), but it exerted a weaker inhibition of the O-methylation
      of 4-OH-E(2). Enzyme kinetic analyses showed that chlorogenic acid and caffeic
      acid inhibited the human liver and placental COMT-mediated O-methylation of
      catechol estrogens with a mixed mechanism of inhibition (competitive plus
      noncompetitive). Computational molecular modeling analysis showed that
      chlorogenic acid and caffeic acid can bind to human soluble COMT at the active
      site in a similar manner as the catechol estrogen substrates. Moreover, the
      binding energy values of these two coffee polyphenols are lower than that of
      catechol estrogens, which means that coffee polyphenols have higher binding
      affinity for the enzyme than the natural substrates. This computational finding
      agreed perfectly with our biochemical data.

PMID- 19095063
TI  - Brain-derived neurotrophic factor (BDNF) overexpression in the forebrain results
      in learning and memory impairments.
AB  - In this study we analyzed the effect on behavior of a chronic exposure to brain
      derived neurotrophic factor (BDNF), by analysing a mouse line overexpressing BDNF
      under the alphaCaMKII promoter, which drives the transgene expression exclusively
      to principal neurons of the forebrain. BDNF transgenic mice and their WT
      littermates were examined with a battery of behavioral tests, in order to
      evaluate motor coordination, learning, short and long-term memory formation. Our
      results demonstrate that chronic BDNF overexpression in the central nervous
      system (CNS) causes learning deficits and short-term memory impairments, both in
      spatial and instrumental learning tasks. This observation suggests that a
      widespread increase in BDNF in forebrain networks may result in adverse effects
      on learning and memory formation.

PMID- 19095064
TI  - Brain and lungs of rats are differently affected by cigarette smoke exposure:
      antioxidant effect of an organoselenium compound.
AB  - Cigarette smoke exposure has been associated with oxidative stress in several
      organs. Antioxidant effect of diphenyl diselenide (PhSe)(2), an organoselenium
      compound, on oxidative damage induced by sub-chronic cigarette smoke exposure in
      brain and lungs of rats was investigated. Animals were exposed 5 times/week to
      one, two, three and four cigarettes for exposure periods of 15 min during the
      first, second, third and fourth weeks. Reactive species (RS) levels, enzymatic
      antioxidant defenses (superoxide dismutase (SOD), catalase (CAT), glutathione
      peroxidase (GPx), glutathione reductase (GR) and glutathione S-transferase (GST)
      activities) and non-enzymatic antioxidant defenses (ascorbic acid and non-protein
      thiol (NPSH) levels) were examined in brain and lungs of rats. An increase in RS
      levels induced by cigarette smoke in both tissues of rats was demonstrated.
      Cigarette smoke altered enzymatic antioxidant defenses (GST, CAT and SOD
      activities) in both tissues, and reduced the non-enzymatic antioxidant defenses
      in lungs. (PhSe)(2) (0.5 mg/kg/day, 5 times/week) restored RS levels and
      antioxidant defenses in brain of rats exposed to cigarette smoke. (PhSe)(2)
      treatment increased NPSH levels, GST and GR activities per se in lungs of rats.
      In conclusion, sub-chronic exposure to cigarette smoke caused alterations in
      antioxidant defense system and a tissue-specific oxidative stress in brain and
      lungs of rats. (PhSe)(2) restored antioxidant defenses in lungs and brain of
      rats.

PMID- 19095065
TI  - Functional expression of Francisella tularensis FabH and FabI, potential
      antibacterial targets.
AB  - Francisella tularensis is an extremely infectious airborne pathogen that has long
      been considered as a potential biological weapon. Enzymes of fatty acid synthesis
      (FAS) pathway are attractive targets for the development of new antibacterial
      agents because of differences between the biosynthesis pathways of bacteria and
      mammals. We report here the first expression of three functional enzymes in F.
      tularensis FAS-II pathway: FabH (3-oxoacyl-acyl carrier protein synthase III)
      which initiates elongation in FAS-II; FabD (Malonyl-CoA-acyl carrier protein
      transacylase) which catalyzes the transfer of a malonyl moiety from malonyl-CoA
      to ACP generating malonyl-ACP, and FabI (enoyl-ACP reductase) which catalyzes the
      reduction of enoyl-acyl-ACP derivatives. The genes encoding the FabD, FabH, and
      FabI were custom synthesized and cloned in pET15b expression vector. Each
      recombinant His-tagged fusion protein was overexpressed by IPTG induction, and
      then purified by affinity chromatography on a Ni-NTA column. The purified FabH
      and FabI have been used as targets for new drug development. Screening of a class
      of indole-2-carboxylic acid compounds has led to the discovery of several new
      compounds with promising activity against F. tularensis FabH or FabI enzymes. For
      example, indole derivative WIUAKP-001 inhibited 80% the FabH enzyme at 40 microM
      with IC(50) value of 2 microM whereas WIUAKP-031 inhibited 98% the FabI enzyme at
      37.5 microM with IC(50) value of 6 microM. These compounds hold great promise for
      future development of new indole derivatives as inhibitors of type II FAS
      enzymes, and as potential new treatment for tularemia.

PMID- 19095066
TI  - The effect of two CpG oligodeoxynucleotides with different sequences on
      haemocytic immune responses of giant freshwater prawn, Macrobrachium rosenbergii.
AB  - A previous study has demonstrated that the intrahaemocytic phenoloxidase (PO)
      activity of the prawn Macrobrachium rosenbergii was enhanced by CpG
      oligodeoxynucleotide (ODN) 2006, but not by os-ODN13. The study described herein
      determined the binding characteristics of the two ODNs to haemocytes. Treating
      haemocytes with FAM-ODN or FAM-ODN plus different concentrations of the same ODN
      revealed that both ODNs specifically bound to haemocytes. Results from haemocytes
      treated with FAM-ODN2006 plus ROX-os-ODN13 in a competitive assay indicated that
      about 91% of haemocytes were simultaneously bound by the two ODNs and that the
      remaining haemocytes were only bound by ODN2006; moreover, ODN2006 binding to
      haemocytes was stronger than that of os-ODN13. To clarify the interactive effect
      of the two ODNs on haemocytic function, mRNA levels of haemocytic genes from
      single or double ODN-injected prawns were determined by semi-quantitative RT-PCR.
      The expression of either the prophenoloxidase (proPO) or peroxinectin (pon) genes
      was elevated by ODN2006 but reduced by os-ODN13; furthermore, ODN2006-increased
      proPO expression was abated following treatment with os-ODN13. In comparison with
      ODN-injected prawns alone, the NF-kappaB inhibitor PDTC reduced the proPO mRNA
      levels induced by ODN2006, but it elevated proPO expression inhibited by os
      ODN13. These results support the notion that os-ODN13 may be able to neutralise
      or negate the enhancing effect of ODN2006 on proPO expression via the NF-kappaB
      signalling pathway as well as an unknown signalling pathway.

PMID- 19095068
TI  - Do women see things differently than men do?
AB  - The aim of the study was to investigate the influence of gender on brain
      activity. Thirty male and 30 female respondents solved simple auditory and visual
      tasks while their electroencephalogram (EEG) was recorded. Also recorded was the
      percentage of oxygen saturation of hemoglobin (%StO(2)) in the respondents'
      frontal brain areas with near-infrared spectroscopy (NIRS). The attended task
      condition was based on the oddball paradigm. Respondents had to mentally count
      infrequent target stimuli - tones or shapes. In the unattended condition they
      just listened to tones or viewed different shapes. Gender related differences in
      EEG activity were only observed in the amplitudes of the early evoked gamma
      response and the P3 component. Women displayed higher amplitudes than men. A
      second finding was that these differences were more pronounced for the visual
      than for the auditory stimuli. No gender related differences were observed in the
      ERP latencies, as well as in the amplitudes of the P1-N1 complex, and the induced
      gamma response. The NIRS data showed that males in their frontal brain areas
      displayed a higher percentage of StO(2) than did females; and males also showed a
      higher increase in %StO(2) during task performance as compared with the resting
      condition. Taken all together the results suggest that the females' visual event
      categorization process is more efficient than in males. The data are discussed in
      the theoretical framework of the evolutionary theory of human spatial sex
      differences.

PMID- 19095067
TI  - Loss of cerebral white matter structural integrity tracks the gray matter
      metabolic decline in normal aging.
AB  - Relationships between structural MRI-based markers of declining cerebral
      integrity, and regional PET measurements of (18)FDG uptake have not been studied
      well in normal aging. In this manuscript we relate changes in cerebral morphology
      to regional cerebral glucose uptake for 14 major cortical areas in 19 healthy
      older individuals (age 59-92 years). Measurements of cerebral integrity included
      gray matter (GM) thickness, sulcal and intergyral spans, fractional anisotropy
      (FA) of water diffusion and volume of hyperintense WM (HWM) lesions. (18)FDG-PET
      measurements were converted to standard uptake values and corrected for partial
      volume artifact. Following this, cortical FDG uptake was significantly correlated
      with several indices of WM integrity that we previously observed to be sensitive
      to cognitive decline in executive function, including intergyral span and HWM
      volumes. Our findings suggest that the age-related decline in white matter
      integrity, observed as increases in HWM lesions, intergyral spans and reduction
      in FA, correlated with a decline in the global and regional cerebral glucose
      uptake. Our findings support the emerging consensus that WM integrity indices are
      sensitive predictors of declining cerebral health in normal aging. Specifically,
      age-related WM degradation in the thinly myelinated association tracts appears to
      track the decreases in global and regional rates of glucose uptake.

PMID- 19095070
TI  - Retina and lens regeneration in anuran amphibians.
AB  - Anuran amphibians can regenerate the retina through differentiation of stem cells
      in the ciliary marginal zone and through transdifferentiation of the retinal
      pigmented epithelium. By contrast, the regeneration of the lens has been
      demonstrated only in larvae of species belonging to the Xenopus genus, where the
      lens regenerates through transdifferentiation of the outer cornea. Retinal
      pigmented epithelium to neural retina and outer cornea to lens
      transdifferentiation processes are triggered and sustained by signaling molecules
      belonging to the family of the fibroblast growth factor. Both during retina and
      lens regeneration there is a re-activation of many of the genes which are
      activated during development of the eye, even though the spatial and temporal
      pattern of gene expression is not a simple repetition of that found in
      development.

PMID- 19095069
TI  - Real-time MR imaging of adeno-associated viral vector delivery to the primate
      brain.
AB  - We are developing a method for real-time magnetic resonance imaging (MRI)
      visualization of convection-enhanced delivery (CED) of adeno-associated viral
      vectors (AAV) to the primate brain. By including gadolinium-loaded liposomes
      (GDL) with AAV, we can track the convective movement of viral particles by
      continuous monitoring of distribution of surrogate GDL. In order to validate this
      approach, we infused two AAV (AAV1-GFP and AAV2-hAADC) into three different
      regions of non-human primate brain (corona radiata, putamen, and thalamus). The
      procedure was tolerated well by all three animals in the study. The distribution
      of GFP determined by immunohistochemistry in both brain regions correlated
      closely with distribution of GDL determined by MRI. Co-distribution was weaker
      with AAV2-hAADC, although in vivo PET scanning with FMT for AADC activity
      correlated well with immunohistochemistry of AADC. Although this is a relatively
      small study, it appears that AAV1 correlates better with MRI-monitored delivery
      than does AAV2. It seems likely that the difference in distribution may be due to
      differences in tissue specificity of the two serotypes.

PMID- 19095071
TI  - The ABC transporter ATR1 is necessary for efflux of the toxin cercosporin in the
      fungus Cercospora nicotianae.
AB  - The Cercospora nicotianae mutant deficient for the CRG1 transcription factor has
      marked reductions in both resistance and biosynthesis of the toxin cercosporin.
      We cloned and sequenced full-length copies of two genes, ATR1 and CnCFP,
      previously identified from a subtractive library between the wild type (WT) and a
      crg1 mutant. ATR1 is an ABC transporter gene and has an open reading frame (ORF)
      of 4368bp with one intron. CnCFP encodes a MFS transporter with homology to
      Cercospora kikuchii CFP, previously implicated in cercosporin export, and has an
      ORF of 1975bp with three introns. Disruption of ATR1 indicated atr1-null mutants
      had dramatic reductions in cercosporin production (25% and 20% of WT levels) in
      solid and liquid cultures, respectively. The ATR1 disruptants also showed
      moderately higher sensitivity to cercosporin. Constitutive expression of ATR1 in
      the crg1 mutant restored cercosporin biosynthesis and moderately increased
      resistance. In contrast, CnCFP overexpression in the mutant did not restore toxin
      production, however, it moderately enhanced toxin resistance. The results
      together indicate ATR1 acts as a cercosporin efflux pump in this fungus and plays
      a partial role in resistance.

PMID- 19095072
TI  - A small G protein Rhb1 and a GTPase-activating protein Tsc2 involved in nitrogen
      starvation-induced morphogenesis and cell wall integrity of Candida albicans.
AB  - Rheb is a new member of the small G proteins of the Ras superfamily in eukaryotic
      organisms and controls various physiological processes. Activity of Rheb is
      regulated by Tsc2, a GTPase-activating protein (GAP). In this study, we have
      identified Candida albicans homologs of Rheb (named as Rhb1) and Tsc2. Deletion
      of the RHB1 gene showed enhanced sensitivity to rapamycin (an inhibitor of TOR
      kinase), suggesting that Rhb1 is associated with the TOR signaling pathway in C.
      albicans. Further analysis indicated RHB1 and TSC2 are involved in nitrogen
      starvation-induced filamentation, likely by controlling the expression of MEP2
      whose gene product is an ammonium permease and a sensor for the nitrogen signal.
      Moreover, we have demonstrated that Rhb1 is also involved in cell wall integrity
      pathway, by transferring signals through the TOR kinase and the Mkc1 MAP kinase
      pathway. Together, this study brings new insights into the complex interplay of
      signaling and regulatory pathways in C. albicans.

PMID- 19095073
TI  - A moderate threonine deficiency differently affects protein metabolism in tissues
      of early-weaned piglets.
AB  - A moderate threonine deficiency may affect differently tissue protein metabolism.
      In this study, we compared protein metabolism in the small and large intestines,
      the liver, and the carcass of piglets (Sus scrofa) pair-fed either a control well
      balanced diet (C: 9.3 g threonine/kg diet) or a low threonine diet (LT: 6.5 g
      threonine/kg diet) for 2 weeks. In the small intestine, the LT diet did not
      modify protein deposition, fractional protein synthesis rate (K(S)) and AA
      protein composition. Ubiquitin mRNA level, a component of the ubiquitin-dependent
      proteolytic pathway, was significantly decreased in the jejunum of the LT
      piglets. Protein deposition measured in the carcass and the colon, and K(S)
      measured in the semitendinosus muscle and the colon, did not differ between LT
      and C piglets. Nevertheless, in these compartments, threonine content was reduced
      indicating deposition of proteins less rich in threonine. In the liver, protein
      retention was reduced, K(S) was increased and AA protein composition was modified
      in the LT compared to the C piglets. In conclusion compared to the other
      compartments, small intestinal protein metabolism seems to be less sensitive to a
      moderate dietary threonine deficiency. This indicates that dietary threonine
      extraction by the small intestine may reduce threonine availability for the other
      tissues when young piglets were fed a diet marginally deficient in threonine.

PMID- 19095074
TI  - cDNA cloning of Japanese flounder stanniocalcin 2 and its mRNA expression in a
      variety of tissues.
AB  - Stanniocalcin 1 (STC1) is a glycoprotein hormone important in the maintenance of
      calcium and phosphate homeostasis in both fishes and mammals. Although two
      related STC genes, STC1 and STC2, were found to be expressed in multiple tissues
      as paracrine regulators in mammals, spatial expression pattern of stc2 mRNA has
      not been elucidated in fishes in contrast to that of clearly described stc1. In
      the present study, we have cloned and characterized a full-length stc2 cDNA from
      Japanese flounder (Paralichyhus olivaceus) ovary and analyzed expression pattern
      of stc2 in both sexes. The flounder stc2 cDNA (1501 nucleotides) encoded a
      putative prehormone of 286 amino acids (aa) with a signal peptide of 20 aa and a
      mature protein of 266 aa. The deduced aa sequence of flounder stc2 showed high
      sequence identity with those of pufferfish, zebrafish, and human (57.7-89.0%),
      whereas it showed less identity with that of flounder stc1 (24.3%). RT-PCR
      analysis revealed that the flounder stc2 gene is expressed in all examined
      tissues including the pituitary, brain, heart, kidney, gills, stomach, spleen,
      skin, dorsal fin, skeletal muscle, liver, corpuscles of Stannius, intestine,
      ovary and testis. Our data indicate that fish stc2 gene, like stc1, is expressed
      in a wide variety of tissues.

PMID- 19095075
TI  - Cloning and characterization of a calmodulin gene (CaM) in crayfish Procambarus
      clarkii and expression during molting.
AB  - Calmodulin (CaM) is a highly conserved calcium (Ca(2+)) binding protein that
      transduces Ca(2+) signals into downstream effects influencing a range of cellular
      processes, including Ca(2+) homeostasis. The present study explores CaM
      expression when Ca(2+) homeostasis is challenged during the mineralization cycle
      of the freshwater crayfish (Procambarus clarkii). In this paper we report the
      cloning of a CaM gene from axial abdominal crayfish muscle (referred to as
      pcCaM). The pcCaM mRNA is ubiquitously expressed but is far more abundant in
      excitable tissue (muscle, nerve) than in any epithelia (gill, antennal gland,
      digestive) suggesting that it plays a greater role in the biology of excitation
      than in epithelial ion transport. In muscle cells the pcCaM was colocalized on
      the plasma membrane with the Ca(2+) ATPase (PMCA) known to regulate intracellular
      Ca(2+) through basolateral efflux. While PMCA exhibits a greater upregulation in
      epithelia (than in non-epithelial tissues) during molting stages requiring
      transcellular Ca(2+) flux (pre- and postmolt compared with intermolt), expression
      of pcCaM exhibited a uniform increase in epithelial and non-epithelial tissues
      alike. The common increase in expression of CaM in all tissues during pre- and
      postmolt stages (compared with intermolt) suggests that the upregulation is
      systemically (hormonally) mediated. Colocalization of CaM with PMCA confirms
      physiological findings that their regulation is linked.

PMID- 19095076
TI  - Activation of insect anti-oxidative mechanisms by mammalian glucagon.
AB  - Resembling the main function of insect adipokinetic hormones (AKHs), the
      vertebrate hormone glucagon mobilizes energy reserves and participates in the
      control of glucose level in the blood. Considering the similarities, the effect
      of porcine glucagon was evaluated in an insect model species, the firebug
      Pyrrhocoris apterus. Using the mouse anti-glucagon antibody, presence of
      immunoreactive material was demonstrated for the first time in the firebug CNS
      and gut by ELISA. Mammalian (porcine) glucagon injected into the adult bugs
      showed no effect on hemolymph lipid level or on the level of AKH in CNS and
      hemolymph, however, it activated an antioxidant response when oxidative stress
      was elicited by paraquat, a diquaternary derivative of 4, 4'-bipyridyl. Glucagon
      elicited the antioxidant response by increasing glutathione and decreasing
      protein carbonyl levels in hemolymph, decreasing both protein carbonyl and
      protein nitrotyrosine levels in CNS. Additionally, when co-injected with
      paraquat, glucagon partially eliminated oxidative stress markers elicited by this
      redox cycling agent and oxidative stressor. This indicates that glucagon might
      induce an antioxidant defense in insects, as recently described for AKH. Failure
      of glucagon to alter AKH level in the bug's body indicates employment of an
      independent pathway without involving the native AKH.

PMID- 19095077
TI  - Apolipoprotein A-I, a hyperosmotic adaptation-related protein in ayu
      (Plecoglossus altivelis).
AB  - Apolipoprotein A-I (apoA-I) is the major protein component of high density
      lipoprotein (HDL) particles in serum and participates in the reverse transport of
      cholesterol from tissues to the liver for excretion. 2DE gel and protein
      identification by MALDI-TOF-MS revealed that an apoA-I-like molecule was
      significantly decreased in the liver of ayu transferred from freshwater (FW) to
      brackish water (BW). A full-length cDNA clone of this protein was subsequently
      isolated. It contains 1209 bp with an open reading frame of 825 bp, coding for
      275 amino acids with MW 31.1 kDa and pI 5.25. Ayu apoA-I had highest similarity
      (88.6% amino acid identity) to that of rainbow smelt. Phylogenetic analysis
      showed that vertebrate apoA-Is formed two major groups, representing mammalian
      bird-amphibian (M-A) and fish apoA-Is respectively. Ayu apoA-I was most closely
      related to rainbow smelt apoA-I. In FW ayu, apoA-I transcripts were present in
      all tested tissues including brain, spleen, liver, kidney, gill, muscle, heart
      and intestine, and highest in liver, brain and intestine. In BW ayu, the
      expression levels of apoA-I gene were significantly decreased and almost totally
      inhibited in spleen, kidney, gill, heart and muscle. Significant down-regulation
      of proteins and mRNA in ayu transferred from FW to BW suggests an involvement in
      hyperosmotic regulation in this species.

PMID- 19095078
TI  - Histophilus somni biofilm formation in cardiopulmonary tissue of the bovine host
      following respiratory challenge.
AB  - Biofilms form in a variety of host sites following infection with many bacterial
      species. However, the study of biofilms in a host is hindered due to the lack of
      protocols for the proper experimental investigation of biofilms in vivo.
      Histophilus somni is an agent of respiratory and systemic diseases in bovines,
      and readily forms biofilms in vitro. In the present study the capability of H.
      somni to form biofilms in cardiopulmonary tissue following experimental
      respiratory infection in the bovine host was examined by light microscopy,
      transmission electron microscopy, immunoelectron microscopy of ultrathin
      cryosections, scanning electron microscopy of freeze-fractured samples, and
      fluorescent in situ hybridization. Biofilms were evident and most prominent in
      the myocardium, and were associated with a large amount of amorphous
      extracellular material. Furthermore, Pasteurella multocida was often cultured
      with H. somni from heart and lung samples. Transposon mutagenesis of H. somni
      strain 2336 resulted in the generation of mutants that expressed more or less
      biofilm than the parent strain. Six mutants deficient in biofilm formation had an
      insertion in the gene encoding for a homolog of filamentous haemagglutinin (FHA),
      predicted to be involved in attachment. Thus, this investigation demonstrated
      that H. somni is capable of forming a biofilm in its natural host, that such a
      biofilm may be capable of harboring other bovine respiratory disease pathogens,
      and that the genes responsible for biofilm formation can be identified by
      transposon mutagenesis.

PMID- 19095079
TI  - Cytosine arabinoside-induced cytogenotoxicity in bone marrow and spermatogonial
      cells of mice and its potential transmission through the male germline.
AB  - Cytosine arabinoside (Ara-C), a widely prescribed antineoplastic drug, especially
      for the treatment of acute myeloid leukaemia, is a pyrimidine analog, in which
      the ribose sugar of cytidine is replaced by arabinose moiety. Ara-C reportedly
      competes with dCTP for incorporation into DNA during synthesis and exhibits
      various cytogenotoxic effects. In the present study, single intraperitoneal
      treatment of three different doses of Ara-C, 100, 150 and 200 mg/kg b.w. of mice,
      selected in accordance with its human therapeutic dose, induced statistically
      significant (p < or = 0.01) and dose dependent increase in the percentages of
      aberrant metaphases and chromosomal aberrations (CAs) at 24h post-treatment, and
      micronuclei (MN) in polychromatic erythrocytes (PCEs) at 30 h post-treatment.
      However, there was no significant change in the mitotic index (MI) at 24h post
      treatment, when compared to that of the control mice. In the male germline, all
      the three doses of Ara-C induced statistically significant (p < or = 0.05 or p <
      or = 0.01) and dose dependent increase in the percentages of aberrant
      spermatogonial metaphases and CAs at 24h post-treatment and statistically
      significant (p < or = 0.01) and dose dependent increase in the percentages of
      aberrant primary spermatocytes at week 4 post-treatment. However, the induction
      of abnormal sperm at week 8 post-treatment was decreased, although significantly.
      The results indicated that Ara-C was clastogenic to both bone marrow and
      spermatogonial cells of mice, and some of its cytogenotoxic effects were found
      transmitted through the male germline, at least up to the formation of primary
      spermatocytes. As the drug is not target specific, the induced cytogenotoxic
      effects of Ara-C on non-cancerous cells of cancer patients retain possible risk
      of recurrence of second malignancy among the post-chemotherapeutic cancer
      survivors. In addition, there is every risk of transmission of some induced
      genetic alterations to the next generation through the gametes of the cancer
      survivors pre-treated with this drug. Therefore, Ara-C essentially be made target
      specific.

PMID- 19095080
TI  - The thermo-sensitive sensilla coeloconica of leaf-cutting ants (Atta
      vollenweideri).
AB  - Social insects show a variety of temperature-guided behaviors. Depending on
      whether heat reaches the sensillum via air movements (convective heat) or as
      radiant heat, specific adaptations of thermo-sensitive sensilla are expected. In
      the present study the morphology and the physiology of thermo-sensitive peg-in
      pit sensilla (S. coeloconica) of the leaf-cutting ant Atta vollenweideri were
      investigated. S. coeloconica are located predominantly in a single cluster on the
      apical antennomere, and connect to the outside through a small aperture. The
      sensory peg is double-walled, embedded in a chamber and innervated by three
      unbranched dendrites. Using tungsten electrodes, activity of the sensory neurons
      was measured. In most cases, the neuron with the largest spike amplitude responds
      to changes in air temperature (convective heat) as well as to radiant heat. In
      response to a drop in air temperature, the neuron shows a phasic-tonic response
      followed by a complete adaptation within 1 min (cold-sensitive neuron). Based on
      their morphology and physiology, it is suggested that the S. coeloconica are
      involved in the recently described thermal orientation behavior of A.
      vollenweideri leaf-cutting ants.

PMID- 19095081
TI  - Is the fish embryo toxicity test (FET) with the zebrafish (Danio rerio) a
      potential alternative for the fish acute toxicity test?
AB  - The fish acute toxicity test is a mandatory component in the base set of data
      requirements for ecotoxicity testing. The fish acute toxicity test is not
      compatible with most current animal welfare legislation because mortality is the
      primary endpoint and it is often hypothesized that fish suffer distress and
      perhaps pain. Animal alternative considerations have also been incorporated into
      new European REACH regulations through strong advocacy for the reduction of
      testing with live animals. One of the most promising alternative approaches to
      classical acute fish toxicity testing with live fish is the fish embryo toxicity
      (FET) test. The FET has been a mandatory component in routine whole effluent
      testing in Germany since 2005 and has already been standardized at the
      international level. In order to analyze the applicability of the FET also in
      chemical testing, a comparative re-evaluation of both fish and fish embryo
      toxicity data was carried out for a total of 143 substances, and statistical
      approaches were developed to evaluate the correlation between fish and fish
      embryo toxicity data. Results confirm that fish embryo tests are neither better
      nor worse than acute fish toxicity tests and provide strong scientific support
      for the FET as a surrogate for the acute fish toxicity test.

PMID- 19095082
TI  - Predicting iron overload in hyperferritinemia.
AB  - BACKGROUND & AIMS: Hyperferritinemia is a common abnormality. This study
      determined the prevalence of hepatic iron overload in subjects of northern
      European origin with hyperferritinemia. METHODS: Fifty-two consecutive subjects
      referred for evaluation of suspected iron overload (serum ferritin level >350
      microg/L) were divided into 3 groups: group 1, increased transferrin saturation
      and no significant hemochromatosis gene product (HFE) mutations (N = 17); group
      2, increased transferrin saturation and C282Y homozygosity or C282Y/H63D compound
      heterozygosity (N = 22); and group 3, normal transferrin saturation and no
      significant HFE mutations (N = 13). All subjects underwent magnetic resonance R2
      relaxometry for quantitation of hepatic iron concentration (HIC). RESULTS: The
      HIC was significantly higher in group 2 subjects (123 +/- 22 micromol/g) compared
      with groups 1 and 3 subjects (39 +/- 4 and 36 +/- 5 micromol/g, respectively) (P
      < .01). Nine of 22 subjects in group 2 had an increase of their HIC to greater
      than 3 times the upper limit of normal compared with none in the other 2 groups
      (P < .01). CONCLUSIONS: An increase of HIC to greater than 3 times the upper
      limit of normal is highly unlikely in hyperferritinemic subjects who do not have
      HFE-related hereditary hemochromatosis or causes of secondary iron overload.

PMID- 19095083
TI  - A retroperitoneal bronchogenic cyst.

PMID- 19095084
TI  - Simple sequence repeats in Haemophilus influenzae.
AB  - Simple sequence repeat (SSRs) of DNA are subject to high rates of mutation and
      are important mediators of adaptation in Haemophilus influenzae. Previous studies
      of the Rd KW20 genome identified the primacy of tetranucleotide SSRs in mediating
      phase variation (the rapid reversible switching of gene expression) of surface
      exposed structures such as lipopolysaccharide. The recent sequencing of the
      genomes of multiple strains of H. influenzae allowed the comparison of the SSRs
      (repeat units of one to nine nucleotides in length) in detail across four
      complete H. influenzae genomes and then comparison with a further 12 genomes when
      they became available. The SSR loci were broadly classified into three groups:
      (1) those that did not vary; (2) those for which some variation between strains
      was observed but this could not be linked to variation of gene expression; and
      (3) those that both varied and were located in regions consistent with mediating
      phase variable gene expression. Comparative analysis of 988 SSR associated loci
      confirmed that tetranucleotide repeats were the major mediators of phase
      variation and extended the repertoire of known tetranucleotide SSR loci by
      identifying ten previously uncharacterised tetranucleotide SSR loci with the
      potential to mediate phase variation which were unequally distributed across the
      H. influenzae pan-genome. Further, analysis of non-tetranucleotide SSR in the 16
      strains revealed a number of mononucleotide, dinucleotide, pentanucleotide,
      heptanucleotide, and octanucleotide SSRs which were consistent with these tracts
      mediating phase variation. This study substantiates previous findings as to the
      important role that tetranucleotide SSRs play in H. influenzae biology. Two
      Brazilian isolates showed the most variation in their complement of SSRs
      suggesting the possibility of geographic and phenotypic influences on SSR
      distribution.

PMID- 19095085
TI  - Human influenza A viruses isolated in South America: genetic relations,
      adamantane resistance and vaccine strain match.
AB  - In order to gain insight into the genetic relations among H3N2 Influenza A virus
      (IAV) circulating in the South American region from 1999 to 2007, to investigate
      the presence of adamantane-resistant strains in this region, and to establish the
      genetic relations among that strains and vaccine strains recommended for the
      Southern hemisphere, 11 haemagglutinin (HA) H3 IAV sequences obtained from
      Uruguayan patients were aligned with corresponding sequences from 68 H3 IAV
      strains isolated in South America and 9 H3 IAV vaccine strains. Maximum
      likelihood phylogenetic tree analysis was performed using the GTR evolutionary
      model. The results of these studies indicate that multiple clades co-circulate
      during most influenza seasons in South America. Strikingly, one strain isolated
      in Uruguay in 2005 and all strains isolated in that country during the 2007
      season bear an HA adamantane-resistant polymorphism. No other strain isolated in
      South America previous to the 2005 season bears that HA characteristic amino acid
      change. Only vaccine strains recommended for the 2007 season were assigned to the
      same cluster with all available IAV isolated in South America for that season.
      Evolution of IAV in this region appears to be shaped by re-introduction of new
      strains.

PMID- 19095086
TI  - Critical involvement of Th1-related cytokines in renal injuries induced by
      ischemia and reperfusion.
AB  - Renal ischemia and reperfusion injury (IRI) is considered an inflammatory
      syndrome. To move forward in its pathogenesis, we exploited the role of several
      cytokines on renal damages triggered by IRI. Specifically to evaluate the role of
      Th1 immune profile in this system, IL-12, IFN-gamma, and IFN-gamma/IL-12
      deficient (KO) mice on C57BL/6 background and their controls were subjected to
      IRI. In each group, blood and kidney samples were harvested. Renal function was
      evaluated by serum creatinine and renal morphometric analyses. Gene expression of
      IL-6 and HO-1 were also investigated by Q-PCR. IFN-gamma KO animals presented the
      highest impairment in renal function compared to controls. Conversely, IL-12 KO
      animals were absolutely protected and, in a lesser extent, IFN-gamma/IL-12 KO
      double knockout was also protected from IRI. Gene expression analyses showed
      higher expression of HO-1, a cytoprotective gene, and IL-6, a pro-inflammatory
      cytokine, in IFN-gamma deficient animals subjected to IRI. Our results confirm
      that Th1 related cytokines such as IL-12 and IFN-gamma are critically involved in
      renal ischemia and reperfusion injury.

PMID- 19095087
TI  - INO80-dependent chromatin remodeling regulates early and late stages of mitotic
      homologous recombination.
AB  - Chromatin remodeling is emerging as a critical regulator of DNA repair factor
      access to DNA damage, and optimum accessibility of these factors is a major
      determinant of DNA repair outcome. Hence, chromatin remodeling is likely to play
      a key role in genome stabilization and tumor suppression. We previously showed
      that nucleosome eviction near double-strand breaks (DSBs) in yeast is regulated
      by the INO80 nucleosome remodeling complex and is defective in mutants lacking
      the Arp8 subunit of INO80. In the absence of homologous donor sequences, RPA
      recruitment to a DSB appeared normal in arp8Delta, but Rad51 recruitment was
      defective. We now show that the early strand invasion step of homologous
      recombination (HR) is markedly delayed in an arp8Delta haploid, but there is only
      a minor defect in haploid HR efficiency (MAT switching). In an arp8Delta diploid,
      interhomolog DSB repair by HR shows a modest defect that is partially suppressed
      by overexpression of Rad51 or its mediator, Rad52. In wild type cells, DSB repair
      typically results in gene conversion, and most gene conversion tracts are
      continuous, reflecting efficient mismatch repair of heteroduplex DNA. In
      contrast, arp8Delta gene conversion tracts are longer and frequently
      discontinuous, indicating defects in late stages of HR. Interestingly, when a
      homologous donor sequence is present, Rad51 is recruited normally to a DSB in
      arp8Delta, but its transfer to the donor is delayed, and this correlates with
      defective displacement of donor nucleosomes. We propose that retained nucleosomes
      at donors destabilize heteroduplex DNA or impair mismatch recognition, reflected
      in delayed strand invasion and altered conversion tracts.

PMID- 19095089
TI  - High bone density in young Hutterite children.
AB  - We previously reported greater than average aBMD in adult Hutterites; however, it
      is unknown whether higher aBMD occurs at younger ages. We examined Hutterite
      children to test the hypotheses that aBMD Z-scores in younger (<15 years)
      Hutterite children would be similar to reference data; but greater in older
      children after they enter the adult workforce at age 15. A secondary aim was to
      determine lifestyle factors associated with bone measures among Hutterite
      children. Hip, femoral neck, and spine BMC and aBMD were measured in 323
      Hutterite children aged 8 through 19 years: 186 (108 girls) were <15 years
      (younger) and 137 (87 girls) were >or=15 years (older). Anthropometric
      measurements and activity and dietary recalls were obtained. Overall, children
      were lighter (Z=-0.29+/-0.72 [mean+/-SD]), shorter (Z=-0.15+/-0.86, and had lower
      BMI's (Z=-0.27+/-0.70) than other South Dakota children residing in the same
      counties (all, p<or=0.002). Older girls and boys had higher percent time in
      moderate+vigorous activity (21+/-10% and 29+/-11% [mean+/-SD]) than younger girls
      and boys (15+/-10% and 18+/-10%, both p<0.001). Younger girls and boys had high
      hip aBMD Z-scores (0.30+/-1.0, 0.44+/-0.97; both greater than 0 at p<or=0.002).
      Younger males had low spine Z-score (-0.27+/-1.15, p=0.04). None of the Z-scores
      for the older ages were different from 0. Controlling for covariates, miles
      walked/day and grip strength were associated with greater hip bone area among
      girls (both, p<0.05). Grip strength was associated with hip and femoral neck BMC
      and hip aBMD among boys (all, p<0.05). Femoral neck bone area was inversely
      associated with calcium intake among boys (p<or=0.05), while higher hip BMC and
      spine BMC and aBMD were associated with increased vitamin D intake (all,
      p<or=0.05). Lean mass was an independent predictor of all bone measures, while
      fat mass was inversely associated with most measures of bone area. In summary,
      contrary to our hypothesis younger Hutterite children had greater hip aBMD Z
      scores than the normative DXA database, whereas older children did not. We
      speculate that high activity levels during the rapid growth phase leads to
      increased bone turnover and bone size; following bone consolidation later in
      young adulthood this will result in greater bone size and aBMD.

PMID- 19095088
TI  - Zfp521 antagonizes Runx2, delays osteoblast differentiation in vitro, and
      promotes bone formation in vivo.
AB  - Zfp521, a 30 C2H2 Kruppel-like zinc finger protein, is expressed at high levels
      at the periphery of early mesenchymal condensations prefiguring skeletal elements
      and in all developing bones in the perichondrium and periosteum, in osteoblast
      precursors and osteocytes, and in chondroblast precursors and growth plate
      prehypertrophic chondrocytes. Zfp521 expression in cultured mesenchymal cells is
      decreased by BMP-2 and increased by PTHrP, which promote and antagonize
      osteoblast differentiation, respectively. In vitro, Zfp521 overexpression reduces
      the expression of several downstream osteoblast marker genes and antagonizes
      osteoblast differentiation. Zfp521 binds Runx2 and represses its transcriptional
      activity, and Runx2 dose-dependently rescues Zfp521's inhibition of osteoblast
      differentiation. In contrast, osteocalcin promoter-targeted overexpression of
      Zfp521 in osteoblasts in vivo results in increased bone formation and bone mass.
      We propose that Zfp521 regulates the rate of osteoblast differentiation and bone
      formation during development and in the mature skeleton, in part by antagonizing
      Runx2.

PMID- 19095090
TI  - Body mass influences cortical bone mass independent of leptin signaling.
AB  - Obesity in humans is associated with increased bone mass. Leptin, a hormone
      produced by fat cells, functions as a sentinel of energy balance, and may mediate
      the putative positive effects of body mass on bone. We performed studies in male
      C57Bl/6 wild type (WT) and leptin-deficient ob/ob mice to determine whether body
      mass gain induced by high fat intake increases bone mass and, if so, whether this
      requires central leptin signaling. The relationship between body mass and bone
      mass and architecture was evaluated in 9-week-old and 24-week-old WT mice fed a
      regular mouse diet. Femora and lumbar vertebrae were analyzed by micro computed
      tomography. In subsequent studies, slowly and rapidly growing ob/ob mice were
      injected in the hypothalamus with a recombinant adeno-associated virus containing
      the leptin gene (rAAV-lep) or a control vector, rAAV-GFP (green fluorescent
      protein). The mice were maintained on a regular control diet for 5 or 7 weeks and
      then subdivided into groups and either continued on the control diet or fed a
      high fat diet (45% of kcal from fat) for 8 weeks. In the WT mice, femoral and
      vertebral bone mass was positively correlated with body mass (Pearson's r=0.65
      0.88 depending on endpoint). rAAV-lep therapy dramatically decreased body mass (
      61%) but increased femur length. However, in the distal femur and lumbar
      vertebra, rAAV-lep therapy reduced cancellous bone volume/tissue volume,
      trabecular number and trabecular thickness, and increased trabecular spacing. The
      high fat diet increased body mass, irrespective of vector treatment. Total femur
      bone volume, length, cross-sectional volume, and cortical volume and thickness
      were increased in mice with increased body mass, independent of rAAV treatment.
      In the distal femur, increased body mass had no effect on cancellous architecture
      and there were no vector x body mass interactions. In WT mice, increased body
      mass resulted in increased (+33%) vertebral cancellous bone volume/tissue volume.
      Increased body mass had minimal independent effect on cancellous vertebral bone
      mass in ob/ob mice. Taken together, these findings suggest that increased body
      mass has a positive effect on femur cortical bone mass that is independent of
      leptin signaling.

PMID- 19095091
TI  - Periostin-like-factor and Periostin in an animal model of work-related
      musculoskeletal disorder.
AB  - Work-related musculoskeletal disorders (WMSDs), also known as overuse injuries,
      account for a substantial proportion of work injuries and workers' compensation
      claims in the United States. However, the pathophysiological mechanisms
      underlying WMSDs are not well understood, especially the early events in their
      development. In this study we used an animal model of upper extremity WMSD, in
      which rats perform a voluntary repetitive reaching and pulling task for a food
      reward. This innovative model provides us an opportunity to investigate the role
      of molecules which may be used either as markers of early diagnosis of these
      disorders, and/or could be targeted for therapeutic purposes in the future.
      Periostin-like-factor (PLF), and Periostin were examined in this study. Both
      belong to a family of vitamin K-dependent gamma carboxylated proteins
      characterized by the presence of conserved Fasciclin domains and not detected in
      adult tissues except under conditions of chronic overload, injury, stress or
      pathology. The spatial and temporal pattern of PLF and Periostin localization was
      examined by immunohistochemistry and western blot analysis in the radius and ulna
      of animals performing a high repetition, high force task for up to 12 weeks and
      in controls. We found that PLF was present primarily in the cellular periosteum,
      articular cartilage, osteoblasts, osteocytes and osteoclasts at weeks 3 and 6 in
      all distal bone sites examined. This increase coincided with a transient increase
      in serum osteocalcin in week 6, indicative of adaptive bone formation at this
      time point. PLF immunoexpression decreased in the distal periosteum and
      metaphysis by week 12, coincided temporally with an increase in serum Trap5b,
      thinning of the growth plate and reduced cortical thickness. In contrast to PLF,
      once Periostin was induced by task performance, it continued to be present at a
      uniformly high level between 3 and 12 weeks in the trabeculae, fibrous and
      cellular periosteum, osteoblasts and osteocytes. In general, the data suggest
      that PLF is located in tissues during the early adaptive stage of remodeling but
      not during the pathological phase and therefore might be a marker of early
      adaptive remodeling.

PMID- 19095092
TI  - President's address: a subspecialist's view of the specialty of general surgery.

PMID- 19095093
TI  - Best poster award: accuracy of surgery residents' interpretation of computed
      tomography scans in trauma.
AB  - BACKGROUND: We evaluated the accuracy of surgery residents in interpreting
      computed axial tomography (CT) scans of trauma patients as compared with
      attending radiologists. METHODS: Residents listed injuries they identified on
      initial CT scans of trauma patients in a time-stamped computerized system before
      the official report becoming available. Head, chest, and abdomen/pelvis CT scans
      were included. We compared the accuracy of these reads with final radiology
      reports. RESULTS: There were 84 injuries in 31 patients. Residents correctly
      identified 25 of 26 (96%) injuries to the head, 28 of 42 (67%) chest injuries,
      and 15 of 16 (94%) injuries to the abdomen and pelvis. The accuracy of resident
      reads of chest CT scans was lower (P = .035) than for other body areas.
      Radiologists' identified 23 of 26 (89%) head injuries, 38 of 42 (90%) chest
      injuries, and 14 of 16 (88%) injuries in the abdomen and pelvis CT scans. None of
      the missed injuries were life threatening or required immediate attention.
      CONCLUSIONS: Surgical residents accurately identify acute injuries on the CT
      scans of trauma victims.

PMID- 19095094
TI  - Jack Barney award: the effect of fatigue on cognitive and psychomotor skills of
      trauma residents and attending surgeons.
AB  - BACKGROUND: Fatigue and sleep deprivation and their effects on surgical
      proficiency have been actively researched areas. Past studies that have focused
      solely on residents have provided an important insight into how fatigue affects
      residents' ability to perform. This study aims to quantify the effect of fatigue
      on attending surgeons. METHODS: To quantify the effect of fatigue on psychomotor
      and cognitive skills of surgical residents and attending surgeons, visiohaptic
      simulations were created to mimic realistic interactions. RESULTS: Both groups
      showed a significant decrement in proficiency measures postcall. When tasks were
      separated based on psychomotor versus cognitive-dominated skills, attending
      surgeons made 25% fewer (P < .05) cognitive errors than residents postcall.
      Psychomotor skills were equally affected in both groups. CONCLUSIONS: Call
      associated fatigue is associated with increased error rates in the cognitive
      skill domain, although less so in attending surgeons compared with their resident
      counterparts.

PMID- 19095095
TI  - The recent decline in mammography rates is limited to low- to average-risk women.
AB  - INTRODUCTION: There has recently been a decline in mammography rates noted in the
      general population. We sought to determine whether similar trends hold in high
      risk populations. METHODS: Mammography rates from the National Health Interview
      Survey for 2000 and 2005 were analyzed for differences among risk-stratified
      populations of women over the age of 40. RESULTS: Although high-risk women (those
      with a personal of family history of breast cancer) were more likely to report
      having had a mammogram than lower risk women, they, too, showed a small decline
      in mammography rates. This, however, did not reach statistical significance. The
      decline in mammography rates in lower risk women, however, was significant and
      correlated with that of the general population. CONCLUSIONS: The decline in
      breast cancer-screening rates noted over the past 5 years has been predominantly
      in lower-risk women.

PMID- 19095096
TI  - Utility of frozen-section analysis of sentinel lymph node biopsy specimens for
      melanoma in surgical decision making.
AB  - BACKGROUND: Debate exists whether frozen-section analysis of sentinel lymph nodes
      (SLNs) for melanoma is an accurate method to detect disease that has metastasized
      to the lymph nodes. The purpose of this study was to evaluate the utility of
      intraoperative frozen section for SLNs in melanoma. METHODS: We reviewed 133
      patients (271 nodes) who underwent SLN biopsy with frozen section for melanoma
      between April 2003 and September 2007. Frozen-section diagnosis was compared with
      final diagnosis to determine concordance between intraoperative and postsurgical
      diagnosis. RESULTS: A total of 11 nodes (8% of patients) were found to have
      metastatic disease. All patients underwent lymph node dissections at the time of
      SLN biopsy. No false-positive SLNs were found on frozen section. The false
      negative rate for SLN biopsy frozen section was 8% (1 of 133 patients).
      CONCLUSIONS: Intraoperative frozen section can be an accurate and reliable tool
      in the right setting for analysis of sentinel nodes in cutaneous melanoma and
      deserves further study.

PMID- 19095097
TI  - Factors influencing time between biopsy and definitive surgery for malignant
      melanoma: do they impact clinical outcome?
AB  - BACKGROUND: Whether time between biopsy and surgery for malignant melanoma
      affects clinical outcomes is sparsely defined. This study evaluated factors
      influencing surgical interval and surgical interval effect on outcomes. METHODS:
      We performed a review of a prospective 10-year, single-institution database.
      RESULTS: There were 473 patients treated for 478 malignant melanomas. The mean
      surgical interval was 30.5 days. The mean thickness was 2.1 mm; 46% of patients
      had a surgical interval of more than 28 days whereas 8% had a surgical interval
      of more than 56 days. Residual melanoma was found at excision in 170 (36%)
      patients. Age, sex, and referral source significantly affected surgical interval,
      however, lesion thickness, sentinel lymph node status, ulceration, and residual
      melanoma at excision did not. In univariate Cox models, neither a surgical
      interval of 28 or less nor less than 56 days showed better overall survival (OS)
      or disease-free survival (DFS). In multivariate Cox models of OS and DFS
      including lesion thickness, sentinel lymph node status, ulceration, and residual
      melanoma at excision, neither a surgical interval of 28 days or fewer nor a
      surgical interval of 56 days or fewer significantly affected outcomes.
      CONCLUSIONS: Age, sex, referral source, and lesion thickness were associated with
      surgical interval. Immediate surgery for malignant melanoma does not
      significantly impact OS or DFS.

PMID- 19095098
TI  - Breast cancer tumor size: correlation between magnetic resonance imaging and
      pathology measurements.
AB  - BACKGROUND: As physicians increasingly use magnetic resonance imaging (MRI) for
      the evaluation of newly diagnosed breast cancers, a review of the correlation
      between MRI and pathology tumor size is imperative. METHODS: A retrospective
      review of 91 breast tumors comparing preoperative MRI tumor size to final
      pathology tumor size was performed. RESULTS: MRI and pathology tumor size were
      positively correlated (R = .650), but with an average overestimation by MRI of
      .63 cm (P <.0001). When stratified by MRI tumor size (< or = 2.0 cm and > 2.0
      cm), a significant difference was found only in tumors greater than 2.0 cm
      (average overestimation = 1.06 cm; P <.0001). This trend continued for the
      histological subtypes of ductal carcinoma in situ (DCIS), invasive ductal
      carcinoma (IDC), and invasive lobular carcinoma (ILC). CONCLUSIONS: MRI tumor
      size correlates with pathology size; however, a significant overestimation
      exists, particularly for tumors > 2.0 cm. Clinicians should therefore use caution
      in relying on MRI tumor size in determining candidacy for breast conservation
      therapy (BCT).

PMID- 19095099
TI  - Selective use of intraoperative sentinel lymph node pathological evaluation in
      breast cancer.
AB  - BACKGROUND: In breast cancer staging, the need for intraoperative sentinel lymph
      (SLN) evaluation is not well established. This study compares intraoperative use
      of touch preparation (TP), frozen section (FS), and factors that may influence
      the selective use of intraoperative SLN analysis. METHODS: Breast cancer patients
      (1998-2007) undergoing SLN evaluation were retrospectively reviewed. RESULTS: Of
      205 SLN procedures, 157 cases underwent intraoperative evaluation, 43% (FS) and
      57% (TP) with positive pathology in 21% and 20%, respectively. The false negative
      case rate was 16% for TP versus 12% for FS. Of T1, low-grade tumors, 9% were
      intraoperatively positive, versus 43% of T2-3, moderate- to high-grade tumors (P
      = .006). Additional positive axillary nodes were found in 43% of the higher risk
      patients versus 0% in the lower risk groups. CONCLUSIONS: Both TP and FS are
      accurate for intraoperative SLN evaluation and can be selectively applied to
      breast cancer staging in low- and high-risk groups.

PMID- 19095100
TI  - Screening cervical spine MRI after normal cervical spine CT scans in patients in
      whom cervical spine injury cannot be excluded by physical examination.
AB  - BACKGROUND: Cervical spine injuries can occur in as many as 10% of patients with
      blunt trauma with mental status changes from closed head injuries. Despite normal
      results on cervical spine computed tomography (CT), magnetic resonance imaging
      (MRI) is often recommended to exclude ligamentous or soft tissue injury. METHODS:
      A retrospective review was conducted of trauma patients admitted to a level I
      trauma center from 2002 to 2006, in whom cervical spine injuries could not be
      excluded by physical examination. All patients with normal results on cervical
      spine CT followed by cervical spine MRI were included in the analysis. RESULTS:
      One hundred twenty patients underwent MRI to examine their cervical spines. Seven
      patients had abnormal MRI findings suggestive of acute traumatic injury. No MRI
      studies led to operative intervention. Screening MRI increased from 1% of
      comatose patients in 2002 to 18% in 2006. CONCLUSIONS: The use of MRI in patients
      with normal results on cervical spine CT does not appear to alter treatment.

PMID- 19095101
TI  - Risk factors for delirium after major trauma.
AB  - BACKGROUND: This study aimed to describe the natural history of delirium after
      major injury, to identify risk factors that predict the development of postinjury
      delirium, and to compare outcome measures in subjects with and without delirium.
      METHODS: A prospective study was performed on patients with an injury severity
      score of 8 or higher admitted to the trauma intensive care unit (ICU) of a level
      I trauma center. Patients underwent daily assessments for delirium with the
      Confusion Assessment Method-ICU. RESULTS: Sixty-nine patients (53 male) were
      enrolled. Delirium occurred in 41 (59%) subjects. Logistic regression found lower
      arrival Glasgow Coma Score (12 +/- 1.0 vs 15 +/- .1; P < .01), increased blood
      transfusions (2.8 +/- .7 vs .5 +/- .3; P < .01), and higher multiple organ
      failure score (1.2 +/- .2 vs .1 +/- .1; P < .01) to be the strongest predictors
      for developing delirium. Outcome measures revealed subjects with delirium had
      longer hospital stays, longer ICU stays, and were more likely require
      postdischarge institutionalization. CONCLUSIONS: Delirium is common in the trauma
      ICU. Higher multiple organ failure score was the strongest predictor of
      postinjury delirium.

PMID- 19095102
TI  - The utility of diagnostic laparoscopy in the evaluation of anterior abdominal
      stab wounds.
AB  - BACKGROUND: To assess if diagnostic laparoscopy (DL) is superior to nonoperative
      modes (serial abdominal examination with/without computed axial tomography [CAT]
      and diagnostic peritoneal lavage) in determining the need for therapeutic
      laparotomy (TL) after anterior abdominal stab wound (ASW). METHODS: Retrospective
      review of ASW patients. Patients were divided into group A (DL/exploratory
      laparotomy) to identify peritoneal violation (PV) and group B (initial
      nonoperative modes). RESULTS: Seventy-three patients met inclusion criteria. In
      group A (n = 38), 29 patients (76%) had PV by DL and underwent exploratory
      laparotomy. Only 10 (35%) underwent TL (sensitivity for PV = 100%; specificity
      and positive predictive value of PV in determining need for TL = 29% and 33%,
      respectively). In group B (n = 35), 7 patients (20%) underwent TL, yielding an
      improved specificity (96%) and positive predictive value (88%). CONCLUSIONS: We
      find no role for DL in the evaluation of ASW patients solely to determine PV.

PMID- 19095103
TI  - Practice management education during surgical residency.
AB  - BACKGROUND: Surgical education has undergone radical changes in the past decade.
      The introductions of laparoscopic surgery and endovascular techniques have
      required program directors to alter surgical training. The 6 competencies are now
      in place. One issue that still needs to be addressed is the business aspect of
      surgical practice. Often residents complete their training with minimal or no
      knowledge on coding of charges or basic aspects on how to set up a practice. We
      present our program, which has been in place over the past 2 years and is
      designed to teach the residents practice management. METHODS: The program begins
      with a series of 10 lectures given monthly beginning in August. Topics include an
      introduction to types of practices available, negotiating a contract, managed
      care, and marketing the practice. Both medical and surgical residents attend
      these conferences. In addition, the surgical residents meet monthly with the
      business office to discuss billing and coding issues. These are didactic sessions
      combined with in-house chart reviews of surgical coding. The third phase of the
      practice management plan has the coding team along with the program director
      attend the outpatient clinic to review in real time the evaluation and management
      coding of clinic visits. RESULTS: Resident evaluations were completed for each of
      the practice management lectures. The responses were recorded on a Likert scale.
      The scores ranged from 4.1 to 4.8 (average, 4.3). Highest scores were given to
      lectures concerning negotiating employee agreements, recruiting contracts,
      malpractice insurance, and risk management. The medical education department has
      tracked resident coding compliance over the past 2 years. Surgical coding
      compliance increased from 36% to 88% over a 12-month period. The program director
      who participated in the educational process increased his accuracy from 50% to
      90% over the same time period. CONCLUSIONS: When residents finish their surgical
      training they need to be ready to enter the world of business. These needs will
      be present whether pursuing a career in academic medicine or the private sector.
      A program that focuses on the business aspect of surgery enables the residents to
      better navigate the future while helping to fulfill the systems-based practice
      competency.

PMID- 19095104
TI  - Impact of a patient care pathway protocol on surgical site infection rates in
      cardiothoracic surgery patients.
AB  - BACKGROUND: We hypothesized that implementing a quality care initiative,
      including peri-incisional antibiotic administration, tight blood glucose control,
      and hair removal with clippers would reduce surgical site infection (SSI) rates
      in patients undergoing coronary artery bypass grafting (CABG), with or without
      valve replacement. METHODS: Patients undergoing CABG were studied
      retrospectively, before (n = 808) and after (n = 674) instituting a patient care
      protocol. The pathway included peri-incisional antibiotics, tight glucose control
      (80 mg/dL-110 mg/dL) throughout intensive care unit (ICU) stays, and hair removal
      with clippers. RESULTS: SSIs were significantly decreased in the experimental
      group (1.5%), compared with the control group (3.5%), (P = .001, odds ratio [OR]
      = .21). Significant independent predictors of infection included diabetes
      mellitus (P = .001, OR = 4.71), Nosocomial Infection Surveillance System (NNIS)
      wound class II (P = .044, OR = 2.07), and female gender (P = .001, OR = 2.83).
      CONCLUSIONS: Protocols implementing timely perioperative antibiotics, tight blood
      glucose control, and avoidance of shaving decrease SSI rates in CABG patients.

PMID- 19095105
TI  - A 2-minute pre-extubation protocol for ventilated intensive care unit patients.
AB  - BACKGROUND: Clinicians often are challenged with safely predicting the optimal
      time of extubation for ventilated patients. Commonly used weaning parameters have
      poor positive predictive value for successful extubation. METHODS: A total of 213
      intubated patients in our 20-bed surgical intensive care unit were enrolled in a
      trial to test a prospective, observational, 2-minute extubation protocol (TMEP).
      Daily measurements were obtained on all intubated patients who met criteria,
      which included adequate oxygenation, systolic blood pressure, heart rate,
      hemoglobin, Glasgow Coma Score greater than 10t, absence of significant
      metabolic/respiratory acidosis, and absence of therapeutic or neurologic
      paralysis. During TMEP, endotracheally intubated patients were physically
      disconnected from the ventilator for a 2-minute period of observation while
      spontaneously breathing room air. Patients were extubated if they tolerated the
      trial without clinically significant desaturation or alteration of vital signs or
      mental status. RESULTS: The TMEP reliably predicted successful extubations in 203
      of 213 patients (95.3%). Patients who required reintubation had a longer
      intensive care unit stay and a longer hospital stay. CONCLUSIONS: TMEP is a
      simple and reliable method of predicting successful extubation.

PMID- 19095106
TI  - A proposed staging system for small bowel carcinoid tumors based on an analysis
      of 6,380 patients.
AB  - BACKGROUND: Little is known about the long-term prognosis of small bowel
      carcinoids because currently no staging system exists. METHODS: A search of the
      Surveillance, Epidemiology and End Results (SEER) database identified 6,380
      patients with small bowel carcinoid tumors from 1977 to 2004. Patients were
      analyzed according to various clinicopathologic factors and a tumor (T1, T2, T3),
      lymph node (N0, N1), and metastasis (M0, M1) staging system was created according
      to these parameters. RESULTS: Among the 6,380 patients, 2,985 women and 3,395
      men, with a median age of 66 years (range 14-98), the median tumor size was 1.9
      cm (range .1-30 cm). Multivariate analysis demonstrated that age, size of the
      primary tumor, and depth of invasion were significant factors. Four stages were
      created according to statistically significant prognostic factors: 13% of
      patients were classified into stage I, 31% into stage II, 16% into stage III, and
      40% into stage IV. Five-year survival rates were 96%, 87%, 74%, and 43% for
      stages I through IV, respectively. CONCLUSIONS: The newly developed TNM staging
      system accurately discriminates prognosis for small bowel carcinoid tumors.

PMID- 19095107
TI  - How important is rigid proctosigmoidoscopy in localizing rectal cancer?
AB  - BACKGROUND: Colonoscopic localization of rectal and rectosigmoid tumors may be
      inaccurate. Rigid proctosigmoidoscopy has been suggested as an adjunctive
      technique to accurately localize rectal tumors as it may alter treatment options.
      METHODS: A retrospective review was performed of patients with rectal and
      rectosigmoid cancer from 2001 to 2006. Patients were stratified into 1 of 4
      anatomic regions based on colonoscopic localization of the tumor. The distances
      of the tumor from the anal verge by colonoscopy were compared with distances
      obtained via rigid proctosigmoidoscopy. RESULTS: Rigid proctosigmoidoscopy
      localization likely changed the treatment options in 21% of lower rectal tumors,
      14% of middle rectal tumors, 38% of upper rectal tumors, and 29% of rectosigmoid
      tumors. Overall, this modality impacted 25% of patients. CONCLUSIONS: Rigid
      proctosigmoidoscopy localization of rectal tumors can significantly change
      treatment options and should be performed on all patients with colonoscopic
      localization of a cancer thought to be in the rectosigmoid or rectum.

PMID- 19095108
TI  - Preoperative performance status predicts outcome following heated intraperitoneal
      chemotherapy.
AB  - BACKGROUND: Peritoneal carcinomatosis has a typical natural history of bowel
      obstruction and death. Significant evidence suggests that cytoreduction with
      heated intraperitoneal chemotherapy (HIPEC) improves long-term survival for these
      tumors. METHODS: A retrospective case series of patients who underwent initial
      HIPEC treatment was performed at 2 moderate-volume centers. Clinicopathologic
      data were reviewed and univariate analyses performed to determine predictors of
      periprocedural complications. RESULTS: Twenty-eight patients underwent HIPEC
      procedures. The most common pathologies were colonic adenocarcinoma and
      pseudomyxoma peritonei. The median preoperative peritoneal cancer index was 9.5.
      Thirteen patients had 34 complications, with no postoperative deaths. Pleural
      effusion and wound infection were the most common complications. Preoperative
      performance status and the extent of disease were predictive of complications.
      CONCLUSIONS: Cytoreduction and HIPEC can be done at moderate-volume centers with
      morbidity and mortality rates comparable with published results from large-volume
      centers. Preoperative performance status and the extent of disease predict
      postoperative complications.

PMID- 19095109
TI  - Association of tobacco and alcohol use with earlier development of colorectal
      cancer: should we modify screening guidelines?
AB  - BACKGROUND: Current guidelines recommend initial colorectal cancer screening at
      age 50 years for average-risk patients. Alcohol and tobacco use can be associated
      with earlier onset of colorectal cancer. We hypothesized an earlier age at
      diagnosis and/or more advanced stage in patients with these habits. METHODS: We
      queried our tumor registry for colorectal cancer diagnosed between January 1997
      and December 2006. Data were analyzed to evaluate effects of alcohol and tobacco
      use. RESULTS: Of 335 colorectal cancer patients, 81% used tobacco, 51% used
      alcohol, 45% used both, and 14% used neither. Current tobacco and alcohol use
      were associated with younger ages at onset of colorectal cancer. Thirteen of 332
      patients were diagnosed with colorectal cancer before age 50 years. All had
      exposure to alcohol and tobacco. Fifty-four percent (7/13) of these patients
      presented at stage 3/4 compared with 34% of the overall population. CONCLUSIONS:
      Modification of screening guidelines to include these habits as "high-risk"
      factors may be indicated.

PMID- 19095110
TI  - The effect of preoperative corticosteroids on peritoneal macrophage function
      after laparoscopic and open abdominal surgery in a rat model.
AB  - BACKGROUND: Peritoneal macrophages play an important role in the immune response
      after abdominal operations. The stress response after these operations has been
      associated with impaired phagocytosis by peritoneal macrophages. This study
      examined the influence of minimally invasive techniques and preoperative
      corticosteroid administration on postoperative peritoneal macrophage phagocytic
      activity. METHODS: After IACUC approval, 66 Sprague Dawley rats were randomly
      divided into 7 groups: baseline animals (B), anesthesia controls (AC), open
      cecectomy (OC), and laparoscopic cecectomy (LC). Within the AC, OC, and LC
      groups, half received intraperitoneal (IP) dexamethasone (10 mg/kg) 1 hour before
      surgery (+S), and the other half received an equal volume of normal saline IP (
      S). Animals were observed postoperatively for 24 hours and were then euthanized.
      Peritoneal macrophages were harvested via intraperitoneal lavage. A phagocytosis
      assay was performed to calculate the net phagocytosis and percent response to the
      effector agent. Statistical analysis was performed using analysis of variance and
      a Student t test between groups. A P value of <.05 was considered significant.
      RESULTS: Significant differences were observed between groups. The B group had a
      response rate of 94.2% +/- 56.7%, which was not different from the AC groups (-S,
      P = .28; +S, P = .16) or the LC-S group (P = .9). The lowest phagocytic activity
      rate was in the OC-S group with a response rate of 33.8% +/- 28.5%. The highest
      phagocytic response rates occurred in the AC +S (145.2% +/- 60.2%) and LC +S
      (198.1% +/- 103.5%). These were not significantly different from each other (P =
      .3). The LC +S group had a significantly higher percent response than all of the
      other groups. The phagocytic response rate of the OC +S group was not different
      from either the AC-S group (P = .07) or the LC-S group (P = .8); however, it was
      less than the AC +S group (P = .02) and the LC +S group (P = .003). CONCLUSION:
      Open cecectomy resulted in greater impairment of the phagocytic activity of
      peritoneal macrophages than laparoscopic cecectomy. The addition of preoperative
      corticosteroids improved phagocytic activity back to baseline function. The
      combination of minimally invasive surgical technique and preoperative
      corticosteroid administration resulted in the greatest postoperative phagocytic
      function of peritoneal macrophages in a rat model.

PMID- 19095111
TI  - Low sensitivity of physical examination findings in necrotizing soft tissue
      infection is improved with laboratory values: a prospective study.
AB  - BACKGROUND: When clinical "hard signs" of necrotizing soft tissue infection
      (NSTI) are present, establishing the diagnosis of NSTI is not difficult. However,
      hard signs of NSTIs are often absent on presentation, thus potentially delaying
      diagnosis and surgical intervention. A prior retrospective study performed at our
      institution demonstrated that admission white blood cell (WBC) count
      >15,400/microL x 10(9)/L and/or serum sodium (Na) <135 mEq/L could help
      differentiate NSTI from non-NSTI. The purpose of this study was to prospectively
      determine how often "hard signs" of NSTI are present and to evaluate how
      knowledge of laboratory parameters influence our surgeons' abilities to diagnose
      and manage NSTI. METHODS: Prospective observational data collection to determine
      the sensitivity of NSTI "hard signs" and administration of a questionnaire in
      which the surgeon was asked whether he believed the patient had an NSTI based on
      physical examination (PE) alone, and then after being informed of the Na level
      and WBC count. RESULTS: Twenty-one patients with a mean age of 41 years had NSTI.
      Mean admission WBC count and Na level were 31,500/microL and 127 mEq/L,
      respectively. Only 9 (43%) had hard signs of NSTI. Suspicion for NSTI increased
      from 9 to 18 (86%) after evaluating laboratory criteria (P = .008). CONCLUSIONS:
      Fewer than half of the patients presented with hard clinical signs of NSTI.
      Admission WBC count >15,400/microL or serum Na <135 mEq/L significantly increased
      suspicion for NSTI and aided early diagnosis.

PMID- 19095112
TI  - Gamma probe identification of normal parathyroid glands during central neck
      surgery can facilitate parathyroid preservation.
AB  - BACKGROUND: We evaluated gamma probe identification (GPI) of sestamibi-labeled
      normal parathyroid glands during central neck surgery. METHODS: GPI was judged to
      be helpful if it resulted in the identification of parathyroid glands not
      identified by direct inspection. RESULTS: GPI was performed in 54 patients and
      was helpful in 20, including 9 patients in whom GPI identified intact parathyroid
      glands in vivo and 11 patients in whom GPI identified incidentally excised
      parathyroid glands ex vivo in the central neck dissection (CND) specimen. GPI was
      more commonly helpful in patients who underwent reoperation (9/16, 56%) compared
      with primary surgery (11/38, 29%; P = .04) and was more commonly helpful in
      patients who underwent CND (17/28, 61%) compared with thyroidectomy without CND
      (2/26, 8%; P < .0001). In 11 patients, normal parathyroid glands were salvaged by
      GPI from the ex vivo CND specimens and autografted. CONCLUSIONS: GPI is a
      relatively simple and effective technique that may help maximize parathyroid
      preservation.

PMID- 19095113
TI  - Reoperative parathyroidectomy in 228 patients during the era of minimal-access
      surgery and intraoperative parathyroid hormone monitoring.
AB  - BACKGROUND: Reoperative parathyroidectomy (R-PTX) in primary hyperparathyroidism
      (1HPT) has increased failure rates and morbidity. This study evaluated R-PTX
      during the era of minimal-access PTX with intraoperative parathyroid hormone
      (IOPTH) monitoring. METHODS: Two thousand sixty-five patients with 1HPT who
      underwent PTX were assessed for R-PTX. Preoperative studies, operative findings,
      and outcomes were evaluated. RESULTS: Two hundred twenty-eight patients underwent
      236 R-PTX procedures. Imaging performed included sestamibi (89%), ultrasound (US;
      56%), computed axial tomography/magnetic resonance imaging (5%), and selective
      venous sampling (1%). Sestamibi was more sensitive than US (84% vs 68%). Curative
      surgery was performed in 89% of patients. IOPTH was 99% sensitive. There was no
      relationship between cure and the following parameters: preoperative calcium or
      PTH levels, persistent or recurrent disease, or use of IOPTH. Solitary gland
      disease and a single previous operation were associated with increased likelihood
      of cure (P = .06). Hypoparathyroidism was decreased using IOPTH monitoring (2% vs
      9%). One patient had recurrent laryngeal nerve palsy. CONCLUSIONS: R-PTX can be
      performed effectively with minimal complications. IOPTH is an accurate predictor
      of cure and may decrease the frequency of permanent hypoparathyroidism.

PMID- 19095114
TI  - Vena cava filter retrieval in therapeutically anticoagulated patients.
AB  - BACKGROUND: Vena cava filters (VCFs) are indicated in patients with active venous
      thromboembolism and are a contraindication to therapeutic anticoagulation. When
      patients can be anticoagulated, VCFs can be removed; however, patients often have
      anticoagulation discontinued during the retrieval procedure, leaving them at risk
      for pulmonary embolism (PE). The authors evaluated their experience with
      retrieving VCFs in therapeutically anticoagulated patients. METHODS: Data from a
      prospectively collected database of patients with VCFs placed between January
      2005 and September 2007 were reviewed. The retrievals in therapeutically
      anticoagulated patients (international normalized ratio, 2.0-3.4) were performed
      using a strict protocol, including preretrieval and postretrieval cavograms. All
      retrievals were performed in the operating room, and patients were discharged
      home the same day and examined within 7 to 14 days. Descriptive statistics
      including means and counts were calculated. RESULTS: One hundred thirteen VCF
      removals occurred during the study period; 62 were attempted on anticoagulated
      patients (42 male and 20 female patients; mean age, 36.5 years). Thirty-five
      patients (56%) had VCFs placed for prophylaxis, 22 (35%) had deep venous
      thromboses or PEs but had contraindications to anticoagulation, and 5 (8%) were
      on anticoagulation, which was discontinued perioperatively for major surgical
      operations. The mean time the filters were in place was 153.7 days (range, 22-684
      days). No extravasation was seen on postretrieval cavography. Eight of 62 removal
      attempts in anticoagulated patients were unsuccessful. One patient had a
      postoperative pneumothorax that was successfully managed without intervention.
      There were no operative bleeding complications, and no hematomas or contusions
      were seen at follow-up. CONCLUSIONS: The retrieval of VCFs in therapeutically
      anticoagulated patients can be performed without complication. Given the
      perioperative risk for PE, anticoagulation should not be discontinued for VCF
      retrieval.

PMID- 19095116
TI  - Noninvasive Doppler ultrasonography for assessing cardiac function: can it
      replace the Swan-Ganz catheter?
AB  - BACKGROUND: Cardiac function, including cardiac index (CI), traditionally has
      been measured by a pulmonary artery catheter (PAC). A noninvasive alternative for
      measuring cardiac function would offer obvious advantages. METHODS: A prospective
      study of trauma and nontrauma patients was performed in a surgical intensive care
      unit over a 3-month period. CI was determined using both a standard PAC and a
      continuous-wave Doppler ultrasound (UTS). The study had 2 phases: phase I was
      nonblinded and phase II was blinded; the correlation between UTS- and PAC-derived
      CI was assessed. RESULTS: A total of 120 paired measurements of CI were observed
      in 31 patients. The UTS-derived CI measurements showed agreement with PAC
      measurements in both phase I and phase II of the study with a bias of .06
      L/min/m(2) +/- .4 L/min/m(2). Paired measurements correlated well in both phase I
      (r = .97, R2 = .95, P < .0001) and phase II (r = .93, R2 = .86, P < .0001) of the
      study. CONCLUSIONS: Doppler UTS correlates well with PAC measurements of CI. This
      noninvasive modality is an accurate and safe alternative to PAC.

PMID- 19095115
TI  - Is there a role for aggressive use of fresh frozen plasma in massive transfusion
      of civilian trauma patients?
AB  - BACKGROUND: Damage control resuscitation (DCR) with early plasma in combat
      casualties requiring massive transfusion (MT) decreases early deaths from
      bleeding. METHODS: To ascertain the potential role of early plasma DCR in
      civilian MT, we queried a prospective traumatic shock database of 383 civilians.
      RESULTS: Ninety-three (24%) of the traumatic shock civilians received a MT, of
      which 26 (28%) died early, predominantly from bleeding within 6 hours.
      Comparatively, this early MT death cohort arrived in more severe shock and were
      coagulopathic (mean INR 2.4). In the critical period of MT (ie, the first 3
      hours), these patients received 20 U of packed red blood cells (PRBCs) but only 4
      U of fresh frozen plasma (FFP). They remained severely acidotic and their
      coagulopathy worsened as they exsanquinated. CONCLUSION: Civilians who arrived in
      traumatic shock, required a MT, and died early had worsening coagulopathy, which
      was not treated. DCR with FFP may have a role in civilian trauma.

PMID- 19095117
TI  - Clinical outcomes of complicated diverticulitis managed nonoperatively.
AB  - BACKGROUND: Surgical resection is typically recommended for patients with
      computed tomography (CT)-confirmed complicated diverticulitis. This study was
      designed to assess outcomes of patients with complicated diverticulitis managed
      nonoperatively. METHODS: A retrospective study covering 14 years evaluated
      patients with complicated diverticulitis diagnosed by CT scan. Patient outcomes,
      including recurrence and need for operations, were reviewed. RESULTS: Of 256
      patients identified, 99 were managed nonoperatively. Forty-six of the 99 patients
      had a recurrent episode of diverticulitis. Of these 46 patients, 20 underwent a
      sigmoid colon resection, with only 1 patient requiring a colostomy for
      obstruction. None of these recurrences resulted in the need for emergency
      resection. CONCLUSIONS: Surgical treatment should play an important role in the
      management of patients with complicated diverticulitis because of the high risk
      of recurrence. However, nonoperative management may be appropriate in a select
      population if age or medical comorbidities preclude a safe operation since the
      need for emergency operation is unlikely.

PMID- 19095119
TI  - Morbidity associated with laparoscopic repair of suprapubic hernias.
AB  - BACKGROUND: Laparoscopic suprapubic hernia repair (LSHR) is frequently a
      technically difficult procedure. This is often due to extensive adhesions from
      multiple previous operations, the necessary wide pelvic dissection, and adequate
      mesh coverage with transfascial suture fixation. The aim of the current study was
      to document the complications and morbidity associated with the repair of
      suprapubic hernias. METHODS: A retrospective review of patients with complex
      suprapubic ventral hernias undergoing laparoscopic repair between 2003 and 2007
      at 2 university-based practices by 1 surgeon at each facility was conducted. The
      operative techniques were similar and included dissection into the space of
      Retzius to mobilize the dome of the bladder, intraperitoneal onlay of mesh using
      a barrier mesh, careful tack fixation to the pubic bone and Cooper's ligaments,
      and extensive transfascial suture fixation of the mesh. RESULTS: A total of 47
      patients were reviewed, 29 women and 18 men, with a mean age of 54 years.
      Patients averaged 3.5 previous abdominal surgeries (SD +/-2.3) and had a mean
      body mass index (BMI) of 35.1 (SD +/-7.5). Previous ventral hernia repairs had
      been performed in 57% of patients. Average defect size was 139.8 cm(2) (SD +/
      126) and average mesh size was 453.8 (SD +/-329.0), with an average hernia-to
      mesh ratio of 3.2. Median length of stay was 3 days with a mean follow-up of 2.6
      months (SD +/-3.1). There were 18 complications (38%): symptomatic seroma (n =
      4), prolonged ileus (n = 2), chronic pain (n = 2), postoperative urinary
      retention (n = 2), enterotomy (n = 1), intraoperative bladder injury (n = 1),
      postoperative urinary tract infection (n = 1), mesh infection (n = 1), rapid
      ventricular rate (n = 1), small bowel obstruction (n = 1), pulmonary embolism (n
      = 1), and pneumonia (n = 1). One patient required conversion to open ventral
      hernia repair, no injury was identified. Recurrence occurred in 3 patients
      (6.3%). The mechanisms of recurrence included reherniation at the level of the
      pubic tubercle, a lateral mesh recurrence in a patient with a high BMI and small
      abdominal excursion, and in a pregnant patient who developed a fixation suture
      hernia. CONCLUSIONS: Laparoscopic suprapubic hernia repair is safe and effective
      with a relatively low recurrence rate, considering the complexity of the repair.

PMID- 19095118
TI  - Management of duodenal and pancreaticobiliary perforations associated with
      periampullary endoscopic procedures.
AB  - BACKGROUND: The purpose of this study was to determine the incidence and outcome
      of pancreaticobiliary and duodenal (PB/D) perforations from periampullary
      endoscopic procedures and to examine whether clinical indexes are predictive of
      the need for operative management. METHODS: A retrospective review compared
      patients who had operative intervention for PB/D perforation with those managed
      nonoperatively. RESULTS: Thirty-two PB/D perforations occurred in 4,919
      procedures (.6%). Twelve (37%) required operation; 20 (63%) were successfully
      managed nonoperatively. Radiographic imaging was not helpful in predicting the
      need for operation. A clinical scoring system was predictive of the need for
      operative management. The length of stay and morbidity rates were higher in the
      operatively managed patients. CONCLUSIONS: Most endoscopic PB/D perforations can
      be successfully managed without operation and, clinical indices are most
      predictive in determining the need for surgery. Further prospective evaluation of
      this scoring system may help guide the need for and timing of operative
      intervention for PB/D perforations.

PMID- 19095120
TI  - Laparoscopic improves perioperative outcomes of antireflux surgery at US academic
      centers.
AB  - BACKGROUND: Open and laparoscopic antireflux surgeries are standard for the
      treatment of gastroesophageal reflux disease (GERD). The in-hospital outcomes of
      laparoscopic and open antireflux procedures were analyzed and compared at US
      academic medical centers. METHODS: Using International Classification of
      Diseases, Ninth Revision, Clinical Modification codes for 5,737 patients with
      GERD that underwent open (n = 1,377) or laparoscopic (n = 4,360) antireflux
      surgery were identified from the University Health-System Consortium Database
      over a 3-year period (2004-2007). Demographic and outcome data measured included
      length of stay, overall complications, in-hospital mortality, observed-to
      expected mortality ratio (risk-adjusted mortality), and hospital costs. RESULTS:
      Laparoscopic antireflux procedures offered significantly lower mean length of
      stay, in-hospital morbidity, and hospital costs. Both procedures had a low
      observed to expected in-hospital mortality. Open surgery was associated with
      significantly higher procedure-related and pulmonary complications. CONCLUSIONS:
      In the context of US academic centers, approximately three quarters of antireflux
      procedures are being performed using the laparoscopic approach. These data
      suggest that laparoscopy has improved in-hospital outcomes when compared with
      open surgery and is preferred for the surgical treatment of GERD.

PMID- 19095121
TI  - Risk of late bleeding following hemorrhoidal banding in patients on
      antithrombotic prophylaxis.
AB  - BACKGROUND: The risk of bleeding following rubber band ligation of internal
      hemorrhoids is 1%-2%. This risk may be increased in patients taking
      antithrombotic therapy. The goal of the current study was to find a safer
      approach to banding without increasing the risk of bleeding. METHODS: This
      retrospective review identified patients undergoing banding while on
      antithrombotic therapy. These medications were held for 7-10 days following the
      procedure. The number of bands placed while on antithrombotic therapy and their
      post band complications were recorded. RESULTS: There were 605 bands placed on
      364 patients taking antithrombotic medications. There were 23 complications
      involving bleeding, a value that was not statistically different from those not
      taking antithrombotic therapy. Patients on clopidogrel experienced 50% of the
      significant bleeding episodes and 18% of the insignificant bleeding episodes.
      CONCLUSIONS: Holding antithrombotic medication following banding appears to
      equalize the risk of bleeding to that of patients not taking antithrombotic
      medications. Patients taking clopidogrel may be at higher risk for bleeding
      complications.

PMID- 19095122
TI  - Hemicorporectomy: back to front.
AB  - Hemicorporectomy involves amputation of the pelvis and lower extremities by
      disarticulation through the lumbar spine with concomitant transection of the
      aorta, inferior vena cava, and spinal cord, as well as creation of conduits for
      diversion of the urinary and fecal streams. A review of the literature reveals
      that the surgical technique has been relatively unchanged since 1960. The
      standard anterior to posterior approach is associated with significant blood loss
      and morbidity, likely contributing to lengthy hospital stay. Herein, we describe
      our back-to-front approach to hemicorporectomy, involving early division of the
      vertebral structures and spinal cord, pre-empting engorgement of Batson's plexus,
      thus minimizing blood loss. In addition, this approach greatly improves exposure
      of the pelvic vessels, allowing for a technically less challenging and safer
      procedure.

PMID- 19095123
TI  - Focal therapy for prostate cancer: analysis by an international panel.

PMID- 19095124
TI  - Evaluating localized prostate cancer and identifying candidates for focal
      therapy.
AB  - Can focal therapy successfully control prostate cancer? Also, if so, which
      patients should be considered eligible? With limited data available from
      relatively few patients, these questions are difficult to answer. At this
      writing, the most likely candidates for focal therapy are patients with low-risk,
      small-volume tumors, located in 1 region or sector of the prostate, who would
      benefit from early intervention. The difficulty lies in reliably identifying
      these men. The larger number of cores obtained in each needle biopsy session has
      increased both the detection of prostate cancer and the potential risk of
      overtreating many patients whose cancers pose very little risk to life or health.
      Urologists typically perform at least a 12-core template biopsy. Although the
      debate continues about the optimal template, laterally and peripherally directed
      biopsies have been shown to improve the diagnostic yield. However, as many as 25%
      of tumors arise anteriorly and can be missed with peripherally directed
      techniques. Prostate cancer tends to be multifocal, even in its earliest stages.
      However, the secondary cancers are usually smaller and less aggressive than the
      index cancer. They appear similar to the incidental cancers found in
      cystoprostatectomy specimens and appear to have little effect on prognosis in
      surgical series. When a single focus of cancer is found in 1 core, physicians
      rightly suspect that more foci of cancer are present in the prostate. Assessing
      the risk in these patients is challenging when determined by the biopsy data
      alone. To predict the presence of a very low-risk or "indolent" cancer, nomograms
      have been developed to incorporate clinical stage, Gleason grade, prostate
      specific antigen levels, and prostate volume, along with the quantitative
      analysis of the biopsy results. Transperineal "mapping" or "saturation" biopsies
      have been advocated to detect cancers missed or underestimated by previous
      transrectal biopsies. This approach could provide the accurate staging, grading,
      and tumor localization needed for a focal therapy program. Nevertheless, for men
      with minimal cancer who are amenable to active surveillance or focal therapy,
      consensus about the most accurate biopsy strategy has not yet been reached.
      Imaging, particularly magnetic resonance imaging and magnetic resonance
      spectroscopic imaging, has been used to assess men with early-stage prostate
      cancer. Large-volume cancers can be seen reasonably well, but small lesions have
      been difficult to detect reliably or measure accurately. Factors such as voxel
      resolution, organ movement, biopsy artifact, and benign changes have limited the
      consistent estimation of the quantitative tumor volume. Nevertheless, magnetic
      resonance imaging and magnetic resonance spectroscopic imaging can aid in
      evaluating patients with prostate cancer being considered for focal therapy by
      providing additional evidence that the patient does not harbor an otherwise
      undetected high-risk, aggressive cancer. In some cases, imaging can usefully
      identify the location of even a limited-sized index cancer. When imaging findings
      are substantiated by mapping biopsy results, confidence in the accurate
      characterization of the cancer is enhanced. Correlating the imaging results with
      tissue changes during and after treatment can be of use in monitoring the
      ablative effects in the prostate and in assessing for tumor recurrence. More work
      is necessary before staging studies can uniformly characterize a prostate cancer
      before therapy, much less reliably identify and locate small-volume cancer within
      the prostate. However, exploring the role of focal ablation as a therapeutic
      option for selected men with low-risk, clinically localized, prostate cancer need
      not await the emergence of perfectly accurate staging studies, any more than the
      application of radical surgery or radiotherapy have. Modern biopsy strategies,
      combined with optimal imaging and nomograms to estimate the pathologic stage and
      risk, taken together, provide a sound basis for the selection of appropriate
      patients for entry into prospective clinical trials of focal therapy.

PMID- 19095125
TI  - Conventional treatments of localized prostate cancer.
AB  - Established therapeutic approaches for clinically localized prostate cancer
      include watchful waiting (active surveillance), radical prostatectomy, and
      radiotherapy. The risk of progression during surveillance is related to the
      initial cancer stage and grade; reasonable evidence has supported the safety and
      feasibility, during a period of 5-10 years, of an active surveillance regimen for
      men with low-risk prostate cancer. The progression rates at >10 years have not
      yet been studied in modern trials. Patients with low-risk tumor characteristics
      can be actively monitored without sacrificing the possibility of cure and without
      being exposed to an undue risk of disease progression, although some patients
      will not accept the emotional burden of living with an untreated cancer. Focal
      ablation might be an attractive alternative to active surveillance for some
      patients with low-risk cancer, if it proves to have minimal adverse effects on
      their quality of life. Radical prostatectomy is an effective form of therapy for
      patients with clinically significant prostate cancer; however, outcomes are
      highly sensitive to variations in surgical technique. Because of the risks of
      perioperative complications and urinary and sexual dysfunction, which appear to
      be as great with robotic-assisted prostatectomy as with any other technique,
      patients with low-risk cancer, especially those >60 years, might be attracted to
      more conservative alternatives, including active surveillance, radiotherapy, and
      focal ablation. External beam radiotherapy is an effective, noninvasive form of
      therapy, but it carries the long-term risks of troublesome bowel and sexual and
      urinary dysfunction. It might be too aggressive for many low-risk cancers
      detected in screened populations. For more aggressive cancers, local recurrence
      after radiotherapy carries substantial morbidity and low rates of long-term
      cancer control. Brachytherapy, a convenient, effective form of radiotherapy, is
      targeted at selected patients with clinically confined cancer and a prostate size
      of <60 g without evidence of extraprostatic extension on imaging. However,
      excellent outcomes require meticulous technique; acute urinary symptoms are
      frequent; and the long-term risks of proctitis and erectile dysfunction are
      comparable to the risks associated with external beam radiotherapy. Androgen
      deprivation therapy is not recommended for men with localized prostate cancer who
      would otherwise be candidates for surgery or radiotherapy, because, even with
      short-term use, the risk of side effects, including osteopenic fracture and major
      cardiovascular events, serious. For locally extensive cancer, androgen
      deprivation therapy should be used alone only for the relief of local symptoms in
      men with a life expectancy of <5 years who are not eligible for more aggressive
      treatment.

PMID- 19095126
TI  - Prostate cancer: epidemiology and health-related quality of life.
AB  - The dramatic increase during the past decade in prostate-specific antigen (PSA)
      testing and prostate biopsies has resulted in the detection of large numbers of
      small lesions, an increase in the incidence of prostate cancer, and an increasing
      incidence-to-mortality ratio. Currently, the risk of being diagnosed with
      prostate cancer is increasingly greater than the risk of dying of it. The
      currently available treatments for prostate cancer are not well suited to
      treating small or indolent tumors. Radical treatment, whether surgery or
      radiotherapy, can eradicate cancer effectively, but these techniques, as well as
      hormonal manipulations, can have adverse effects on patients' health and quality
      of life. Watchful waiting, or "active surveillance," has the advantage of
      avoiding the deleterious effects on quality of life, but it confronts patients
      with the emotional burden of living with an untreated cancer that could progress
      and metastasize. For active surveillance, no established, objective criteria are
      available for progression that would signal the optimal time for therapeutic
      intervention. PSA levels in patients with low-risk, small-volume cancers are more
      indicative of the size of the benign prostate or the presence of inflammation
      than of changes in the volume or growth of the cancer, and PSA levels inherently
      fluctuate, creating a low signal-to-noise ratio until the cancer is very large.
      Little risk exists in waiting to confirm a sustained increase in the PSA level
      before proceeding with a diagnostic biopsy. This policy would decrease the number
      of unnecessary biopsies, but still diagnose men within a safe timeframe. In
      studies controlled for age and comorbidity, the survival rate for patients with
      low-risk prostate cancer mirrors that expected in the general population. This
      holds true across cohorts of patients, whatever the treatment used. Because no
      strong medical or scientific evidence supports any particular ablative technique
      for low-risk prostate cancer, no standard of care has been universally accepted.
      Therefore, practice patterns are heterogeneous and depend more on the
      availability of treatments than on the features of the disease itself.

PMID- 19095127
TI  - New treatments for localized prostate cancer.
AB  - Interest in focal therapy for prostate cancer has recently been renewed owing to
      downward stage migration, improved biopsy and imaging techniques, and the
      prevalence of either unifocal cancer or a dominant cancer with secondary tumors
      of minimal malignant potential. Several techniques have potential for focal
      ablation of prostate cancer. Cryotherapy has been used for some time as primary
      therapy for complete ablation of the prostate or local recurrence after
      radiotherapy. Enthusiasm for cryotherapy as the primary therapy has been tempered
      by the uncertainty about complete ablation of the cancer, the frequent
      persistence of measurable prostate-specific antigen levels after the procedure,
      and a high rate of erectile dysfunction. Studies have reported "focal ablation"
      of prostate cancer with cryotherapy, targeting 1 side of the gland to eliminate a
      cancer confined to that side with less risk of urinary or sexual complications.
      Whether cryotherapy has sufficient power to eradicate focal cancer and can be
      targeted with sufficient accuracy to avoid damage to surrounding structures
      remains to be demonstrated in prospective clinical trials. High-intensity focused
      ultrasound (HIFU) has been used widely in Europe for complete ablation of the
      prostate, especially in elderly men who are unwilling or unable to undergo
      radical therapy. For low- or intermediate-risk cancer, the short- and
      intermediate-term oncologic results have been acceptable but need confirmation in
      prospective multicenter trials presently underway. Whole gland therapy with
      transrectal ultrasound guidance has been associated with a high risk of acute
      urinary symptoms, often requiring transurethral resection before or after HIFU.
      Adverse effects on erectile function seem likely after a therapy that depends on
      heat to eradicate the cancer, but erectile function after HIFU has not been
      adequately documented with patient-reported questionnaires. HIFU holds promise
      for focal ablation of prostate cancer. As with cryotherapy, focal HIFU should
      reduce the adverse sexual, urinary, and bowel effects of whole gland ablation.
      New techniques are being developed to allow HIFU treatment under real-time
      guidance using magnetic resonance imaging, which could improve the precision and
      reduce the adverse effects further. Another promising technique, currently in
      clinical trials, is vascular-targeted photodynamic therapy, which has been used
      for whole gland ablation of locally recurrent cancer after radiotherapy and, more
      recently, for focal ablation of previously untreated cancer. In combination with
      a new, systemically administered photodynamic agent, laser light is delivered
      through fibers introduced into the prostate under ultrasound guidance. This
      technique does not heat the prostate but destroys the endothelial cells and
      cancer by activating the photodynamic agent. Damage to surrounding structures
      appears to be limited and can be controlled by the duration and intensity of the
      light. We have reviewed the principles of focal therapy and these new therapeutic
      modalities.

PMID- 19095128
TI  - Interpreting the results of cost-effectiveness studies.
AB  - In developed nations, health care spending is an increasingly important economic
      and political issue. The discipline of cost-effectiveness (CE) analysis has
      developed over several decades as a tool for objectively assessing the value of
      new medical strategies, by simultaneously examining incremental health benefits
      in light of incremental costs. The underlying goal of CE research is to allow
      clinicians and policymakers to make more rational decisions regarding clinical
      care and resource allocation. This review will provide the reader with an
      understanding of the theoretical underpinnings of CE analysis, the types of
      analyses commonly performed and reported in the medical literature, some
      important strengths and weaknesses of different analytical approaches, and key
      principles in the interpretation of CE results. Key principles reviewed include
      the impact of analytic perspective, the importance of proper incremental
      comparisons, the effect of time horizon, and methods for exploring and describing
      uncertainty. Illustrative examples from the cardiology literature are discussed.

PMID- 19095129
TI  - Bosentan for treatment of inoperable chronic thromboembolic pulmonary
      hypertension: BENEFiT (Bosentan Effects in iNopErable Forms of chronIc
      Thromboembolic pulmonary hypertension), a randomized, placebo-controlled trial.
AB  - OBJECTIVES: Our goal was to investigate the effect of treatment with the oral
      dual endothelin receptor antagonist bosentan on the hemodynamics and exercise
      capacity of patients with chronic thromboembolic pulmonary hypertension (CTEPH).
      BACKGROUND: CTEPH is characterized by vascular obstruction and remodeling,
      leading to increased pulmonary vascular resistance (PVR). Although pulmonary
      endarterectomy (PEA) is potentially curative, medical therapy is needed in
      patients with inoperable disease or persistent/recurrent pulmonary hypertension
      after PEA. METHODS: The BENEFiT (Bosentan Effects in iNopErable Forms of chronIc
      Thromboembolic pulmonary hypertension) study was a double-blind, randomized,
      placebo-controlled study in CTEPH including patients with either inoperable CTEPH
      or persistent/recurrent pulmonary hypertension after PEA (>6 months after PEA).
      Independent coprimary end points were change in PVR as a percentage of baseline
      and change from baseline in 6-min walk distance after 16 weeks of treatment with
      bosentan or placebo. Secondary end points included change from baseline in World
      Health Organization functional class and other hemodynamic parameters. RESULTS:
      One hundred fifty-seven patients were enrolled and randomized: 80 to placebo, 77
      to bosentan. A statistically significant treatment effect (TE) of bosentan over
      placebo on PVR was demonstrated: -24.1% of baseline (95% confidence interval
      [CI]: -31.5% to -16.0%; p < 0.0001). Total pulmonary resistance (TE: -193
      dynxsxcm(-5); 95% CI: -283 to -104 dyn.s.cm(-5); p < 0.0001) and cardiac index
      (TE: 0.3 lxmin(-1)xm(-2); 95% CI: 0.14 to 0.46 lxmin(-1)xm(-2); p = 0.0007)
      improved. Mean TE on 6-min walk distance was +2.2 m (95% CI: -22.5 to 26.8 m; p =
      0.5449). Bosentan treatment was well tolerated. CONCLUSIONS: This study
      demonstrated a positive TE of bosentan on hemodynamics in this patient
      population. No improvement was observed in exercise capacity. Further trials are
      needed to define the role of medical therapy in patients with CTEPH (Bosentan
      Effects in Inoperable Forms of Chronic Thromboembolic Pulmonary Hypertension;
      NCT00313222).

PMID- 19095130
TI  - Diagnostic accuracy of 64-slice computed tomography coronary angiography: a
      prospective, multicenter, multivendor study.
AB  - OBJECTIVES: This study sought to determine the diagnostic accuracy of 64-slice
      computed tomographic coronary angiography (CTCA) to detect or rule out
      significant coronary artery disease (CAD). BACKGROUND: CTCA is emerging as a
      noninvasive technique to detect coronary atherosclerosis. METHODS: We conducted a
      prospective, multicenter, multivendor study involving 360 symptomatic patients
      with acute and stable anginal syndromes who were between 50 and 70 years of age
      and were referred for diagnostic conventional coronary angiography (CCA) from
      September 2004 through June 2006. All patients underwent a nonenhanced calcium
      scan and a CTCA, which was compared with CCA. No patients or segments were
      excluded because of impaired image quality attributable to either coronary motion
      or calcifications. Patient-, vessel-, and segment-based sensitivities and
      specificities were calculated to detect or rule out significant CAD, defined as
      >or=50% lumen diameter reduction. RESULTS: The prevalence among patients of
      having at least 1 significant stenosis was 68%. In a patient-based analysis, the
      sensitivity for detecting patients with significant CAD was 99% (95% confidence
      interval [CI]: 98% to 100%), specificity was 64% (95% CI: 55% to 73%), positive
      predictive value was 86% (95% CI: 82% to 90%), and negative predictive value was
      97% (95% CI: 94% to 100%). In a segment-based analysis, the sensitivity was 88%
      (95% CI: 85% to 91%), specificity was 90% (95% CI: 89% to 92%), positive
      predictive value was 47% (95% CI: 44% to 51%), and negative predictive value was
      99% (95% CI: 98% to 99%). CONCLUSIONS: Among patients in whom a decision had
      already been made to obtain CCA, 64-slice CTCA was reliable for ruling out
      significant CAD in patients with stable and unstable anginal syndromes. A
      positive 64-slice CTCA scan often overestimates the severity of atherosclerotic
      obstructions and requires further testing to guide patient management.

PMID- 19095131
TI  - Limitations of computed tomography coronary angiography.

PMID- 19095133
TI  - Psychological distress as a risk factor for cardiovascular events:
      pathophysiological and behavioral mechanisms.
AB  - OBJECTIVES: This study sought to estimate the extent to which behavioral and
      pathophysiological risk factors account for the association between psychological
      distress and incident cardiovascular events. BACKGROUND: The intermediate
      processes through which psychological distress increases the risk of
      cardiovascular disease (CVD) are incompletely understood. An understanding of
      these processes is important for treating psychological distress in an attempt to
      reduce CVD risk. METHODS: In a prospective study of 6,576 healthy men and women
      (ages 50.9 +/- 13.1 years), we measured psychological distress (using the 12-item
      version of the General Health Questionnaire >or=4) and behavioral (smoking,
      alcohol, physical activity) and pathophysiological (C-reactive protein,
      fibrinogen, total and high-density lipoprotein cholesterol, obesity,
      hypertension) risk factors at baseline. The main outcome was CVD events
      (hospitalization for nonfatal myocardial infarction, coronary artery bypass,
      angioplasty, stroke, heart failure, and CVD-related mortality). RESULTS:
      Cigarette smoking, physical activity, alcohol intake, C-reactive protein, and
      hypertension were independently associated with psychological distress. There
      were 223 incident CVD events (63 fatal) over an average follow-up of 7.2 years.
      The risk of CVD increased in relation to presence of psychological distress in
      age- and sex-adjusted models (hazard ratio: 1.54, 95% confidence interval: 1.09
      to 2.18, p = 0.013). In models that were adjusted for potential mediators,
      behavioral factors explained the largest proportion of variance ( approximately
      65%), whereas pathophysiological factors accounted for a modest amount (C
      reactive protein approximately 5.5%, hypertension, approximately 13%).
      CONCLUSIONS: The association between psychological distress and CVD risk is
      largely explained by behavioral processes. Therefore, treatment of psychological
      distress that aims to reduce CVD risk should primarily focus on health behavior
      change.

PMID- 19095132
TI  - The relationship of left ventricular mass and geometry to incident cardiovascular
      events: the MESA (Multi-Ethnic Study of Atherosclerosis) study.
AB  - OBJECTIVE: The purpose of this study was to evaluate the relationship of left
      ventricular (LV) mass and geometry measured with cardiac magnetic resonance
      imaging (MRI) to incident cardiovascular events in the MESA (Multi-Ethnic Study
      of Atherosclerosis) study. BACKGROUND: MRI is highly accurate for evaluation of
      heart size and structure and has not previously been used in a large
      epidemiologic study to predict cardiovascular events. METHODS: A total of 5,098
      participants in the MESA study underwent cardiac MRI at the baseline examination
      and were followed up for a median of 4 years. Cox proportional hazard models were
      constructed to predict the end points of coronary heart disease (CHD), stroke,
      and heart failure (HF) after adjustment for cardiovascular risk factors. RESULTS:
      A total of 216 incident events were observed during the follow-up period. In
      adjusted models, the end points of incident CHD and stroke were positively
      associated with increased LV mass-to-volume ratio (CHD, hazard ratio [HR]: 2.1
      per g/ml, p = 0.02; stroke, HR: 4.2 per g/ml, p = 0.005). In contrast, LV mass
      showed the strongest association with incident HF events (HR: 1.4 per 10%
      increment, p < 0.0001). The HF events occurred primarily in participants with LV
      hypertrophy, that is, >or=95th percentile of LV mass (HR: 8.6, 95% confidence
      interval: 3.7 to 19.9, reference group <50th percentile of LV mass). CONCLUSIONS:
      The LV size was related to incident HF, stroke, and CHD in this multiethnic
      cohort. Whereas body size-adjusted LV mass alone predicted incident HF,
      concentric ventricular remodeling predicted incident stroke and CHD.

PMID- 19095134
TI  - Psychological distress and cardiovascular risk: what are the links?

PMID- 19095136
TI  - Left-dominant arrhythmogenic cardiomyopathy: an under-recognized clinical entity.
AB  - OBJECTIVES: We sought to investigate the clinical-genetic profile of left
      dominant arrhythmogenic cardiomyopathy (LDAC). BACKGROUND: In the absence of
      coronary disease and left ventricular (LV) systolic dysfunction, lateral T-wave
      inversion and arrhythmia of LV origin are often considered benign. Similarly,
      chest pain with enzyme release might be attributed to viral myocarditis. We
      hypothesized that these abnormalities might be manifestations of the "left
      dominant" subtype of arrhythmogenic right ventricular cardiomyopathy. METHODS:
      The 42-patient cohort was established through clinical evaluation of individuals
      with unexplained (infero)lateral T-wave inversion, arrhythmia of LV origin,
      and/or proven LDAC/idiopathic myocardial fibrosis in the family. RESULTS:
      Patients presented from adolescence to age >80 years with arrhythmia or chest
      pain but not heart failure. Desmosomal mutations were identified in 8 of 24
      families (15 of 33 patients). Magnetic resonance findings included LV late
      enhancement in a subepicardial/midwall distribution, corresponding to fibrofatty
      replacement and fibrosis on histopathology. Fifty percent had previously been
      misdiagnosed with viral myocarditis, dilated cardiomyopathy (DCM), hypertrophic
      cardiomyopathy, or idiopathic ventricular tachycardia. Arrhythmic events included
      presentation with ventricular fibrillatory arrest in 1 patient and 2 instances of
      sudden cardiac death during follow-up. CONCLUSIONS: Arrhythmogenic cardiomyopathy
      is distinguished from DCM by a propensity towards arrhythmia exceeding the degree
      of ventricular dysfunction. The left-dominant subtype is under-recognized owing
      to misattribution to other disorders and lack of specific diagnostic criteria.
      Clinicians are alerted to the possibility of LDAC in patients of any age with
      unexplained arrhythmia of LV origin, (infero)lateral T-wave inversion, apparent
      DCM (with arrhythmic presentation), or myocarditis (chest pain and enzyme rise
      with unobstructed coronary arteries).

PMID- 19095137
TI  - Expanding the spectrum of arrhythmogenic cardiomyopathy.

PMID- 19095135
TI  - Nonmyocardial production of ST2 protein in human hypertrophy and failure is
      related to diastolic load.
AB  - OBJECTIVES: This study was designed to investigate: 1) relationships between
      serum ST2 levels and hemodynamic/neurohormonal variables; 2) myocardial ST2
      production; and the 3) expression of ST2, membrane-anchored ST2L, and its ligand,
      interleukin (IL)-33, in myocardium, endothelium, and leukocytes from patients
      with left ventricular (LV) pressure overload and congestive cardiomyopathy.
      BACKGROUND: Serum levels of ST2 are elevated in heart failure. The relationship
      of ST2 to hemodynamic variables, source of ST2, and expression of ST2L and IL-33
      in the cardiovascular system are unknown. METHODS: Serum ST2 (pg/ml; median
      [25th, 75th percentile]) was measured in patients with LV hypertrophy (aortic
      stenosis) (n = 45), congestive cardiomyopathy (n = 53), and controls (n = 23).
      ST2 was correlated to N-terminal pro-brain natriuretic peptide, C-reactive
      protein, and hemodynamic variables. Coronary sinus and arterial blood sampling
      determined myocardial gradient (production) of ST2. The levels of ST2, ST2L, and
      IL-33 were measured (reverse transcriptase-polymerase chain reaction) in
      myocardial biopsies and leukocytes. The ST2 protein production was evaluated in
      human endothelial cells. The IL-33 protein expression was determined
      (immunohistochemistry) in coronary artery endothelium. RESULTS: The ST2 protein
      was elevated in aortic stenosis (103 [65, 165] pg/ml, p < 0.05) and congestive
      cardiomyopathy (194 [69, 551] pg/ml, p < 0.01) versus controls (49 [4, 89] pg/ml)
      and correlated with B-type natriuretic peptide (r = 0.5, p < 0.05), C-reactive
      protein (r = 0.6, p < 0.01), and LV end-diastolic pressure (r = 0.38, p < 0.03).
      The LV ST2 messenger ribonucleic acid was similar in aortic stenosis and
      congestive cardiomyopathy versus control (p = NS). No myocardial ST2 protein
      gradient was observed. Endothelial cells secreted ST2. The IL-33 protein was
      expressed in coronary artery endothelium. Leukocyte ST2L and IL-33 levels were
      highly correlated (r = 0.97, p < 0.001). CONCLUSIONS: In human hypertrophy and
      failure, serum ST2 correlates with the diastolic load. Though the heart,
      endothelium, and leukocytes express components of ST2/ST2L/IL-33 pathway, the
      source of circulating serum ST2 is extra-myocardial.

PMID- 19095138
TI  - Long-term effects of fenofibrate on carotid intima-media thickness and
      augmentation index in subjects with type 2 diabetes mellitus.
AB  - OBJECTIVES: The aim of this substudy was to ascertain whether long-term treatment
      with fenofibrate reduces surrogate measures of atherosclerosis, biomarkers of
      inflammation, and endothelial activation in patients with type 2 diabetes.
      BACKGROUND: Some fibrates may decrease cardiovascular events, improve endothelial
      function, and reduce levels of acute-phase proteins. In the FIELD (Fenofibrate
      Intervention and Event Lowering in Diabetes) study, fenofibrate failed to
      decrease the primary end point of coronary events in patients with type 2
      diabetes. METHODS: A total of 170 patients with type 2 diabetes of the FIELD
      Helsinki cohort were randomly assigned to micronized fenofibrate 200 mg/day or
      placebo in a double-blind design. Carotid intima-media thickness (IMT) and the
      augmentation index (a measure of large artery stiffness) were measured at
      baseline and at second- and fifth-year visits. Plasma levels of interleukin (IL)
      6, C-reactive protein (CRP), serum amyloid A (SAA), secretory phospholipase A2
      IIA (SPLA2), E-selectin, vascular cellular adhesion molecule (VCAM)-1, and
      intercellular adhesion molecule (CAM)-1 were determined by commercial enzyme
      linked immunosorbent assay kits at the same visits. RESULTS: IMT and the
      augmentation index increased similarly in both treatment groups during the study.
      Plasma levels of CRP, IL-6, SPLA2, SAA, VCAM-1, ICAM-1, and E-selectin remained
      unchanged in both groups. CONCLUSIONS: Fenofibrate treatment was not associated
      with beneficial changes in IMT, augmentation index, or biomarkers of inflammation
      and endothelial function. (Fenofibrate Intervention and Event Lowering in
      Diabetes; NCT00132886).

PMID- 19095140
TI  - Additional lipid lowering trials using surrogate measurements of atherosclerosis
      by carotid intima-media thickness: more clarity or confusion?

PMID- 19095141
TI  - Cardiac amyloid.

PMID- 19095139
TI  - Effect of statins alone versus statins plus ezetimibe on carotid atherosclerosis
      in type 2 diabetes: the SANDS (Stop Atherosclerosis in Native Diabetics Study)
      trial.
AB  - OBJECTIVES: This secondary analysis from the SANDS (Stop Atherosclerosis in
      Native Diabetics Study) trial examines the effects of lowering low-density
      lipoprotein cholesterol (LDL-C) with statins alone versus statins plus ezetimibe
      on common carotid artery intima-media thickness (CIMT) in patients with type 2
      diabetes and no prior cardiovascular event. BACKGROUND: It is unknown whether the
      addition of ezetimibe to statin therapy affects subclinical atherosclerosis.
      METHODS: Within an aggressive group (target LDL-C <or=70 mg/dl; non-high-density
      lipoprotein cholesterol <or=100 mg/dl; systolic blood pressure <or=115 mm Hg),
      change in CIMT over 36 months was compared in diabetic individuals >40 years of
      age receiving statins plus ezetimibe versus statins alone. The CIMT changes in
      both aggressive subgroups were compared with changes in the standard subgroups
      (target LDL-C <or=100 mg/dl; non-high-density lipoprotein cholesterol <or=130
      mg/dl; systolic blood pressure <or=130 mm Hg). RESULTS: Mean (95% confidence
      intervals) LDL-C was reduced by 31 (23 to 37) mg/dl and 32 (27 to 38) mg/dl in
      the aggressive group receiving statins plus ezetimibe and statins alone,
      respectively, compared with changes of 1 (-3 to 6) mg/dl in the standard group (p
      < 0.0001) versus both aggressive subgroups. Within the aggressive group, mean
      CIMT at 36 months regressed from baseline similarly in the ezetimibe (-0.025 [
      0.05 to 0.003] mm) and nonezetimibe subgroups (-0.012 [-0.03 to 0.008] mm) but
      progressed in the standard treatment arm (0.039 [0.02 to 0.06] mm), intergroup p
      < 0.0001. CONCLUSIONS: Reducing LDL-C to aggressive targets resulted in similar
      regression of CIMT in patients who attained equivalent LDL-C reductions from a
      statin alone or statin plus ezetimibe. Common carotid artery IMT increased in
      those achieving standard targets. (Stop Atherosclerosis in Native Diabetics Study
      [SANDS]; NCT00047424).

PMID- 19095142
TI  - Looking back.

PMID- 19095143
TI  - Endothelialization and late stent thrombosis in diabetics.

PMID- 19095146
TI  - Influence of symptoms and age on the predictive value of coronary artery calcium
      scanning.

PMID- 19095147
TI  - Survey results: a decade of change in professional life in cardiology: a 2008
      report of the ACC women in cardiology council.

PMID- 19095148
TI  - Melanoma and pigmented lesions, part 1.

PMID- 19095149
TI  - Melanoma epidemiology and trends.
AB  - Rising incidence rates of cutaneous melanoma have been observed during the last
      four decades in white populations worldwide. The cancer statistics in the United
      States have revealed 6 cases per 100,000 and year at the beginning of the 1970s
      and 18 cases per 100,000 inhabitants and year at the beginning of 2000,
      demonstrating a threefold increase in incidence rates. Incidence rates in central
      Europe increased in the same time period from 3 to 4 cases to 10 to 15 cases per
      100,000 inhabitants and year, which is very similar to the increase in the United
      States. Cohort studies from several countries indicate that the trend of
      increasing incidence rates will continue in the future for at least the next 2
      decades; thus, an additional doubling of incidence rates is expected. The highest
      incidence rates have been reported from Australia and New Zealand, from 40 to 60
      cases per 100,000 inhabitants and year. Mortality rates likewise slightly
      increased in the United States and in Europe during the 1970s and 1980s. In the
      1990 s, however, a leveling off of mortality rates was observed in many
      countries. Simultaneously, a clear decrease of Breslow tumor thickness was
      reported in the United States and European countries. This development indicates
      improved early recognition of cutaneous melanoma, which is presently the main
      factor for a more favorable prognosis.

PMID- 19095150
TI  - The value of screening in melanoma.
AB  - The incidence of cutaneous melanoma has increased substantially in most white
      populations during the past several decades. Despite improvements in the early
      recognition of melanoma and the use of novel diagnostic techniques that enhance
      our diagnostic capabilities, disease-related mortality remains a significant
      public health issue. In the absence of effective treatment approaches for
      advanced disease, the best means for reducing deaths by melanoma are screening as
      well as professional and public education. The role of population-or community
      based screening remains controversial, but evidence from self-selected screening
      campaigns, health care professional surveillance, and specialized pigmented
      lesions clinics underscores the value of screening and early detection programs,
      particularly in high-risk groups. Annual screening campaigns coupled with intense
      media promotion have become commonplace in many countries, and despite their low
      yield of melanoma detection, the dissemination of educational material and
      information to the public during these events is important in increasing public
      awareness. Future directions should include using screening campaigns to target
      middle-aged and older men and persons of lower socioeconomic status, who suffer
      most from the burden of the disease and its associated mortality. On a worldwide
      scale, comprehensive educational and screening campaigns should be implemented or
      intensified in underserved areas and geographic regions with lower survival
      rates, such as Eastern European countries. A better understanding of the biology
      of the disease, already occurring with notable strides, will help us to define
      better those individuals who will benefit most from screening and early detection
      efforts. Technologic advances and new diagnostic modalities will afford a more
      reliable and vigilant surveillance of high-risk individuals, whereas the wide use
      of the Internet will enhance the distribution of relevant information to the
      public with the ultimate goal of achieving a better control of melanoma.

PMID- 19095151
TI  - Dermoscopy: what's new?
AB  - Dermoscopy has been described as a useful tool for the early diagnosis of
      melanoma and the differential diagnosis of pigmented lesions of the skin. This
      has been proven by three independent meta analyses of the literature. Dermoscopy
      is a fast evolving field with a high number of new publications every year.
      Initially, the use of dermoscopy was limited to pigmented lesions, but it is used
      more and more in other situations. It has become an important tool for the
      diagnosis of nail pigmentations, hair and scalp disorders, and so forth. In this
      article we try to provide an update on recent trends and developments in
      dermoscopy.

PMID- 19095153
TI  - Melanoma and genetics.
AB  - As the incidence of malignant melanoma continues to increase and with the
      completion of the sequencing of the human genome, there have been increasing
      efforts to identify the "melanoma gene(s)." Although some patients and families
      have significantly increased risks due to genetic predisposition, most melanoma
      cases are sporadic and likely result from low to moderate risk genetic factors.
      This review focuses on the genes that cover the greatest risk of developing
      melanoma. It is important to remember that many--if not most--cases of melanoma
      are the result of undiscovered variants. The strongest genetic risk for the
      development of melanoma results from heritable alterations in cyclin-dependent
      kinase inhibitor 2A (CDKN2A) gene, which encodes two separate but related
      proteins, p16/INK4a and p14/ARF. These proteins help regulate cell division and
      apoptosis, both of which are necessary to maintain cellular homeostasis. Other
      important genes include CDK4/6 and retinoblastoma (RB1), which encode downstream
      proteins in the same pathway as p16/INK4a and p14/ARF. Finally, we discuss the
      relative importance of the melanocortin 1 receptor (MC1R) gene as a moderate risk
      factor for melanoma. Although great advances have been made in understanding the
      molecular basis and genetic predisposition of melanoma, many questions still
      remain to be answered. Someday soon, it will be possible to predict a patient's
      risk of melanoma by DNA analysis; however, it is important to reconcile our
      tremendous technologic capabilities with documented clinical utility.

PMID- 19095154
TI  - Melanoma prognostic factors found in the dermatopathology report.
AB  - Significant prognostic information is available in a routine melanoma
      dermatopathology report. Features that are enumerated in the pathology report and
      that portend a potentially poorer prognosis are older age, site (acral, head,
      neck), male sex, increasing Breslow tumor thickness, increasing Clark's level,
      ulceration, increasing number of mitoses, vertical growth phase, regression,
      absence of a host inflammatory response, increased tumor vascularity,
      angiotropism, vascular invasion, neurotropism, marked atypia, and satellite
      metastasis.

PMID- 19095152
TI  - Current and emerging technologies in melanoma diagnosis: the state of the art.
AB  - Relative to other specialties, dermatologists have been slow to adopt advanced
      technologic diagnostic aids. Most skin disease can be diagnosed by simple visual
      inspection, and the skin is readily accessible for a diagnostic biopsy.
      Diagnostic aids, such as total body photography and dermoscopy, improve the
      clinician's ability to diagnose melanoma beyond unaided visual inspection,
      however, and are now considered mainstream methods for early detection. Emerging
      technologies such as in vivo reflectance confocal microscopy are currently being
      investigated to determine their utility for noninvasive diagnosis of melanoma.
      This review summarizes the currently available cutaneous imaging devices and new
      frontiers in noninvasive diagnosis of skin disease. We anticipate that multimodal
      systems that combine different imaging technologies will further improve our
      ability to detect, at the bedside, melanoma at an earlier stage.

PMID- 19095155
TI  - New techniques in dermatopathology that help to diagnose and prognosticate
      melanoma.
AB  - Routine light microscopy supplemented with immunohistochemistry in cases of
      metastatic or spindle cell melanoma are standards of care for the diagnosis and
      staging of melanoma. Not all melanocytic tumors can be confidently classified as
      melanoma or benign nevus by histology, however. In addition, tumor thickness and
      ulceration, the current American Joint Classification on Cancer prognosticators
      for primary cutaneous (stages I and II) melanoma used in clinical practice, do
      not perfectly predict an individual's clinical course. Recent advances in
      molecular techniques and bioinformatics mandate testing and use of novel methods
      for the detection, diagnosis, and classification of melanocytic tumors that can
      accurately predict tumor behavior and help in selecting the most optimal and
      individualized therapy.

PMID- 19095156
TI  - The "dysplastic" nevus.
AB  - Dysplastic nevi have become an increasing focus clinically, with evidence that
      they are associated with a higher risk of developing melanoma. However, there
      still is contention regarding the significance of dysplastic nevi. This
      contribution provides an overview of the history, epidemiology, genetics,
      clinical and histologic features, and procedures for clinical management of
      dysplastic nevi. Since dysplastic nevi were described originally in 1978, a great
      deal of research has examined the epidemiology of these lesions and the genetic
      factors related to the development of dysplastic nevi. However, there is
      disagreement regarding the clinical management of dysplastic nevi and the
      histologic definition of dysplastic nevi. Current recommendations include
      preventative measures, such as sun protection and careful surveillance and
      biopsies of suspicious lesions as needed. The advent of new technologies, such as
      computer-vision systems, have the potential to significantly change treatment of
      dysplastic nevi in the future.

PMID- 19095157
TI  - Nevi and melanoma in the pregnant woman.
AB  - Multiple difficult questions arise when a pregnant woman presents to the
      dermatologist with a changing melanocytic nevus or melanoma. Our review of the
      literature provides some insight into these issues. We recommend that a changing
      pigmented lesion in the pregnant woman should be biopsied promptly and can be
      safely performed. Women who have dysplastic nevus syndrome require closer
      monitoring during pregnancy. For the pregnant woman with a confirmed, localized
      melanoma, prognosis does not appear to be affected by pregnancy. Likewise,
      limited data indicate that pregnancy before or after a diagnosis of melanoma does
      not affect prognosis. Wide local excision may be performed safely, but if
      sentinel lymph node mapping and biopsy is indicated, the technique and safety of
      this procedure in the pregnant woman remains controversial. There appears to be
      no absolute contraindication to the prescription of oral contraceptive pills or
      hormone replacement therapy in someone who has been previously diagnosed with
      melanoma if no reasonable alternative exists.

PMID- 19095158
TI  - Ocular melanoma: relatively rare but requiring respect.
AB  - Primary ocular melanoma can involve the uveal tract, conjunctiva, eyelid, or
      orbit. Uveal melanoma is the most common ocular melanoma and carries a serious
      prognosis, especially if the tumor is medium or large in size. Conjunctival
      melanoma manifests on the surface of the eye and has been increasing in
      incidence. Eyelid and primary orbital melanoma are the least common variants.
      Early diagnosis from annual ocular examination by an experienced ophthalmologist
      and treatment strategies are reviewed.

PMID- 19095159
TI  - Tales of bugs, delusions of parasitosis, and what to do.
AB  - Delusions of parasitosis are usually a monosymptomatic dermatopsychiatric
      disorder manifested by the fixed false belief that insects are crawling over the
      body producing an intractable itch. Also known as parasitophobia, this disease
      can also be associated with other psychiatric disorders, such as schizophrenia or
      obsessive compulsive disorders. In most cases, the delusion is encapsulated and
      other mental functions remain intact. Parasitophobia is usually seen in middle
      aged women and has proven a vexing problem for dermatologists to treat because
      patients are often reluctant to obtain a psychiatric consultation and wary of
      taking antipsychotic or antidepressant medication. Four patients with this
      disorder illustrate the problem, provide a new approach to understanding the
      precipitating factors in the onset of the disease, and permit the introduction of
      a previously undescribed therapy, escitalopram (Lexapro, Forest Pharmaceuticals,
      New York, NY), a selective serotonin reuptake inhibitor with less side effects
      than the previously favored therapy with pimozide.

PMID- 19095160
TI  - Constantine the Great and leprosy: fact or fiction?

PMID- 19095161
TI  - Postpartum depressive symptoms and smoking relapse.
AB  - BACKGROUND: Smokers with depressive symptoms are more likely to relapse after
      attempting to quit than those without depressive symptoms. Little is known about
      the relationship between depressive symptoms and relapse during the postpartum
      period; thus the aim of the present study is to assess the relationship between
      postpartum smoking relapse and depressive symptoms. METHODS: Analysis of 2004
      Pregnancy Risk Assessment Monitoring System (PRAMS) data from women in 16 states
      who reported smoking 3 months before pregnancy and reported abstinence from
      smoking during the last 3 months of pregnancy (n=2566). For women experiencing
      postpartum depressive symptoms, chi-square tests were computed for homogeneity of
      distribution between two groups (sustained abstinence versus relapsed) and an OR
      for relapsing during the postpartum period. Potential confounders, including
      demographic characteristics, intensity of smoking before pregnancy, and time
      since delivery, were computed. RESULTS: Compared to women who did not experience
      postpartum depressive symptoms, women who did were 1.86 (95% CI=1.31, 2.65) times
      as likely to relapse during the postpartum period. After adjusting for
      demographic characteristics, intensity of smoking, and time since delivery, the
      association decreased slightly (adjusted OR=1.77, 95% CI=1.21, 2.59).
      CONCLUSIONS: Women who quit smoking during pregnancy may be more likely to
      relapse if they experience depressive symptoms. Further research is needed into
      the screening and treatment of postpartum depressive symptoms as a possible
      method for preventing postpartum smoking relapse.

PMID- 19095163
TI  - Automated telephone counseling for parents of overweight children: a randomized
      controlled trial.
AB  - BACKGROUND: Interactive technologies have the potential to increase the reach and
      frequency of practical clinical interventions that assist the parents of
      overweight and at-risk children to promote healthy lifestyle behaviors for their
      families. DESIGN: A practical RCT evaluated the relative effectiveness of three
      interventions to support parents of overweight or at-risk children to change the
      home environment to foster more healthful child eating and activity behaviors,
      thereby reducing child BMI and BMI z-scores. A secondary purpose was to determine
      the patterns of use and potential dose effect for the highest-intensity
      intervention. SETTING/PARTICIPANTS: Parent-and-child (aged 8-12 years) dyads
      (N=220) who received care from Kaiser Permanente Colorado were assigned randomly
      to one of the three Family Connections (FC) interventions: FC-workbook, FC-group,
      or FC-interactive voice response (IVR) counseling. MAIN OUTCOME MEASURES: Child
      BMI z-scores, as well as symptoms of eating disorders and body image, were
      assessed at baseline, 6 months, and 12 months. RESULTS: The BMI z-scores of
      children assigned to the FC-IVR intervention were the only ones that decreased
      from baseline to 6 months (0.07 SD) and from baseline to 12 months (0.08 SD,
      p<0.05). Children whose parents completed at least six of the ten FC-IVR
      counseling calls had decreased BMI z-scores to a greater extent than children in
      the FC-workbook or FC-group interventions at both 6 months (p<0.05) and 12 months
      (p<0.01). No intervention increased child symptoms of eating disorders or body
      dissatisfaction at any time point. CONCLUSIONS: This trial demonstrated that
      automated telephone counseling can support the parents of overweight children to
      reduce the extent to which their children are overweight. TRIAL REGISTRATION:
      NCT00433901.

PMID- 19095162
TI  - Coronary heart disease attributable to passive smoking: CHD Policy Model.
AB  - BACKGROUND: Passive smoking is a major risk factor for coronary heart disease
      (CHD), and existing estimates are out of date due to recent and substantial
      changes in the level of exposure. OBJECTIVE: To estimate the annual clinical
      burden and cost of CHD treatment attributable to passive smoking. OUTCOME
      MEASURES: Annual attributable CHD deaths, myocardial infarctions (MI), total CHD
      events, and the direct cost of CHD treatment. METHODS: A Monte Carlo simulation
      estimated the CHD events and costs as a function of the prevalence of CHD risk
      factors, including passive-smoking prevalence and a low (1.26) and high (1.65)
      relative risk of CHD due to passive smoking. Estimates were calculated using the
      CHD Policy Model, calibrated to reproduce key CHD outcomes in the baseline Year
      2000 in the U.S. RESULTS: At 1999-2004 levels, passive smoking caused 21,800
      (SE=2400) to 75,100 (SE=8000) CHD deaths and 38,100 (SE=4300) to 128,900
      (SE=14,000) MIs annually, with a yearly CHD treatment cost of $1.8 (SE=$0.2) to
      $6.0 (SE=$0.7) billion. If recent trends in the reduction in the prevalence of
      passive smoking continue from 2000 to 2008, the burden would be reduced by
      approximately 25%-30%. CONCLUSIONS: Passive smoking remains a substantial
      clinical and economic burden in the U.S.

PMID- 19095164
TI  - Intimate partner violence in Latina and non-Latina women.
AB  - BACKGROUND: No single study has delineated the prevalence of intimate partner
      violence (IPV) over multiple time periods for Latina versus non-Latina women and
      compared the health of abused Latina women to the health of abused non-Latina
      women using multiple health indicators. The objective of this study was to
      describe the prevalence of IPV over multiple time periods and the association
      between lifetime IPV exposure and current health in Latina and non-Latina women.
      METHODS: A total of 3429 women (mean age=47 years) were randomly sampled from a
      large U.S. healthcare system; 139 (4%) were Latina. During a telephone survey,
      past-5-year and past-year IPV prevalence was assessed using five questions on
      physical and psychological abuse from the Behavioral Risk Factor Surveillance
      System (BRFSS), and ten questions from the Women's Experience with Battering
      Scale; lifetime IPV prevalence was assessed using the BRFSS questions. Current
      physical, social, and mental health was assessed using well-validated
      questionnaires. RESULTS: Prevalence of IPV for Latina versus non-Latina women
      was, respectively: 44.6% vs 44% lifetime; 20.1% vs 14.5% for the past 5 years;
      and 11.5% vs 7.8% for the past year. In models adjusted for age and income, women
      with a lifetime IPV history had significantly worse health compared to non-abused
      women across many health indicators; for example, Latina women with a lifetime
      IPV history had Short Form-36 Health Survey (SF-36) subscale scores that were
      5.62 (mental health) to 7.77 (vitality) points lower than those for non-abused
      Latina women; depression prevalence more than two times higher; and more physical
      symptoms. Adverse IPV-related health was significantly worse for Latina than non
      Latina women for overall mental health functioning (p<0.02), vitality (p<0.01),
      and emotional functioning (p<0.01) according to SF-36. CONCLUSIONS: This
      exploratory study showed that IPV is common in Latina and non-Latina women, and
      adverse IPV-related mental health was pronounced in Latina women.

PMID- 19095165
TI  - Rural-urban differences in injury hospitalizations in the U.S., 2004.
AB  - BACKGROUND: Despite prior research demonstrating higher injury-mortality rates
      among rural populations, few studies have examined the differences in nonfatal
      injury risk between rural and urban populations. The objective of this study was
      to compare injury-hospitalization rates between rural and urban populations using
      population-based national estimates derived from patient-encounter data. METHODS:
      A cross-sectional analysis of the 2004 Nationwide Inpatient Sample was conducted
      in 2007. Rural-urban classifications were determined based on residence. SUDAAN
      software and U.S. Census population estimates were used to calculate nationally
      representative injury-hospitalization rates. Injury rates between rural and urban
      categories were compared with rate ratios and 95% CIs. RESULTS: An estimated 1.9
      million (95% CI=1,800,250-1,997,801) injury-related hospitalizations were
      identified. Overall, injury-hospitalization rates generally increased with
      increasing rurality; rates were 27% higher in large rural counties (95% CI=10%,
      44%) and 35% higher in small rural counties (95% CI=16%, 55%). While
      hospitalization rates for assaults were highest in large urban counties, the
      rates for unintentional injuries from motor vehicle traffic, falls, and
      poisonings were higher in rural populations. Rates for self-inflicted injuries
      from poisonings, cuttings, and firearms were higher in rural counties. The total
      estimated hospital charges for injuries were more than $50 billion. On a per
      capita basis, hospital charges were highest for rural populations. CONCLUSIONS:
      These findings highlight the substantial burden imposed by injury on the U.S.
      population and the significantly increased risk for those residing in rural
      locations. Prevention and intervention efforts in rural areas should be expanded
      and should focus on risk factors unique to these populations.

PMID- 19095166
TI  - The comparative effectiveness of heart disease prevention and treatment
      strategies.
AB  - BACKGROUND: Policymakers must be able to calculate the comparative effectiveness
      of interventions to control heart disease if they are to optimize the population
      impact of programmatic initiatives. METHODS: A model was created to calculate the
      number of deaths that would be prevented or postponed if perfect care for heart
      disease prevention and treatment were achieved--that is, the elimination of risk
      factors and the prescription of all effective medications before and between
      acute events, and the delivery of all effective therapies to individuals
      suffering an acute heart disease event. The impact of perfect care was calculated
      for a hypothetic population aged 30-84 years with risk-factor levels, event
      rates, current patterns of behavior, levels of treatment, and mortality rates
      resembling those of the U.S. The analysis was performed in 2007 and 2008.
      RESULTS: In this population, 44% of all deaths were due to heart disease. Perfect
      care before the first heart disease event would prevent or postpone 33% of all
      deaths. Perfect care between acute events would prevent or postpone 23% of all
      deaths. Perfect care during acute events would prevent or postpone 8% of all
      deaths. CONCLUSIONS: This direct comparison of heart disease prevention and
      treatment strategies indicates that nearly 90% of the impact from perfect care
      for heart disease would accrue from interventions before and between acute
      events. The impact of risk-factor interventions before or between events is
      amplified by the fact that these interventions also reduce the risk of death from
      other chronic diseases.

PMID- 19095167
TI  - Variability in diagnostic accuracy can be estimated using simple population
      weighting.
AB  - OBJECTIVE: Diagnostic accuracy of a quantitative diagnostic test at a given
      numeric cutoff is dependent on the type of population (e.g., chronic, referrals,
      or screening) under investigation. Simple weighted averages calculated from a
      single study sample may be used to assess variability in accuracy in different
      types of populations. STUDY DESIGN AND SETTING: We evaluated the accuracy of the
      4-variable Modification of Diet in Renal Disease (MDRD) Study equation as a
      diagnostic test to separate stage 1 and 2 chronic kidney disease (>or=60 mL/min
      per 1.73 m(2)) from stage 3-5 (<60 mL/min per 1.73 m(2) requiring treatment to
      prevent progression) in a sample of 850 patients referred for determination of
      glomerular filtration rate (GFR). Using population weighting, we also estimated
      the accuracy of the MDRD equation when the GFR distribution typically found in
      screening situations was mimicked. RESULTS: Estimated diagnostic accuracy of the
      MDRD equation varied substantially for different population types (sensitivity
      range 82%-97%, specificity 67%-93%; figures include the original MDRD study).
      CONCLUSIONS: Reports of diagnostic accuracy should include estimates of the
      variability of diagnostic accuracy, using different real or tentative population
      distributions. Population weighting is a useful tool for this purpose.

PMID- 19095168
TI  - Traditional assessment of health outcome following total knee arthroplasty was
      confounded by response shift phenomenon.
AB  - OBJECTIVES: To examine the existence, direction, and effect of response shift as
      measured by the total score of Western Ontario and McMaster Universities
      Osteoarthritis Index (WOMAC) and SF-36 physical and mental component score
      domains at 6 months and 1 year after primary total knee arthroplasty (TKA). STUDY
      DESIGN AND SETTING: Consecutive candidates participated in the study. In line
      with the Then-test design, two sets of questionnaires were completed at 6 months
      and 1 year postoperatively. Patients were divided into three groups on the basis
      of minimal clinically important differences (MCIDs). Parametric and nonparametric
      statistics and generalized mixed effects models were used. RESULTS: Two hundred
      and thirty-six patients completed the study. The magnitude of response shift
      increased over time for SF-36 physical and mental component scores. The
      traditional unadjusted presurgical and 1-year postsurgical assessment failed to
      reveal any mental health improvement, whereas the adjusted treatment effect
      demonstrated statistically significant changes. CONCLUSION: Response shift
      phenomenon increases with time in patients undergoing orthopedic interventions.
      The traditional pre- and post-assessment of joint replacement surgery may be
      confounded by a change in perspective and in internal standards of measurement in
      patients undergoing surgery. Response shift has substantial impact on measuring
      recovery in this population.

PMID- 19095169
TI  - Increased African-American involvement in vaccine studies.

PMID- 19095170
TI  - Journal of Shoulder and Elbow Surgery. Editor's note.

PMID- 19095171
TI  - Comparison of perioperative complications in patients with and without rheumatoid
      arthritis who receive total elbow replacement.
AB  - Total elbow replacement is a well-recognized surgical treatment for patients with
      advanced rheumatoid arthritis (RA) of the elbow. At present, there is minimal
      literature outlining the perioperative complications associated with total elbow
      replacement. We endeavored to identify complication rates and hospital
      disposition differences between patients with and without RA who received a total
      elbow replacement. Data from the Nationwide Inpatient Sample was used to capture
      3,617 patients who received a total elbow arthroplasty between 1988-2005. Of
      these, 888 had a primary diagnosis of RA and were compared against patients
      without RA. Analyses addressed perioperative complications and hospital
      disposition factors, such as charges and length of stay. Overall complication
      rates were very low with only 2 variables, respiratory complications (P = .01)
      and renal failure (P = .04) demonstrating significantly worse outcomes in
      patients without RA (P = .01). Patients without RA had also had longer lengths of
      stay (P < 0.01). There were 9 reported perioperative deaths. The findings suggest
      that the perioperative complications of a total elbow replacement for all
      patients studied are few and that outcomes in patients with RA are nearly
      equivalent to those in patients without RA.

PMID- 19095172
TI  - Morphologic analysis of the medullary canal in rheumatoid elbows.
AB  - Total elbow arthroplasty is a standard approach for patients with arthritic
      elbows. To design appropriate stems for elbow prostheses, it is important to
      understand the shape of the medullary canals. The purpose of this study was to
      evaluate the shape and size of the medullary canals from normal cadavers and
      rheumatoid arthritis patients. These canals were measured based on geometric
      constructions of the 3-dimensional bone models generated from computed tomography
      images. The cross-sectional area of the medullary canals in rheumatoid arthritis
      patients decreased near the elbow joint as a result of morphologic changes after
      a long-standing inflammatory reaction. When designing the press-fit component of
      the humerus, an increase in the width of the transverse diameter of the
      intramedullary stem could increase stability in the canal. In contrast, for the
      ulnar component, such morphologic changes would impose difficulty in placing the
      press-fit model despite an anatomically designed stem. Therefore, a cement
      technique would be required for improved stabilization of the ulnar component.

PMID- 19095173
TI  - Corrective dome osteotomy for cubitus varus and valgus in adults.
AB  - A corrective dome osteotomy was performed in 19 adult patients for cubitus varus
      and valgus deformity. The mean age at operation was 31.1 years and the mean
      follow-up was 41 months. The average postoperative carrying angle in 16 patients
      with cubitus varus was 6.1 degrees (range, 1-10 degrees), an average correction
      of 24 degrees (range, 5-36 degrees). The average postoperative carrying angle in
      3 patients with cubitus valgus was 6.7 degrees (range, 6-7 degrees), an average
      correction of 29.3 degrees (range, 29-30 degrees). None of the patients had
      recurrence of deformity, unsightly scarring, or a prominent lateral or medial
      condyle at final follow-up. An excellent result was achieved in 13 patients and
      good in 6. We conclude that corrective dome osteotomy with secure fixation using
      plates and screws is a reliable option for cubitus varus or valgus deformity in
      adults.

PMID- 19095174
TI  - Type II error in the shoulder and elbow literature.
AB  - Although the randomized controlled trial (RCT) has been recognized as the gold
      standard for comparing interventions, trials that fail to show a difference
      between 2 interventions may suffer from type II error. This study was conducted
      to determine if the published RCTs in the shoulder and elbow literature have
      sufficient power to minimize potential type II error and conclude accurately that
      no difference between interventions exists. We searched Medline for RCTs with
      negative results in Arthroscopy, the Journal of Bone and Joint Surgery
      (American), and the Journal of Shoulder and Elbow Surgery (1994 through 2007)
      with strict inclusion criteria pertaining to care of shoulder and elbow injuries.
      Eligible studies were analyzed for type II error and the power of their
      conclusions. The power to detect a difference, if in fact one was present, was
      only 41% (common standard, 80%). It is a critically important distinction to
      conclude no difference was observed rather than no true difference between
      interventions exists.

PMID- 19095175
TI  - After rotator cuff tears, the remaining (intact) tendons are mechanically
      altered.
AB  - Although presumed, damage in the remaining (intact) rotator cuff tendons in the
      presence of an isolated supraspinatus tendon tear or multiple tendon tear has not
      been well studied. This study used an animal model of multiple rotator cuff
      tendon tears to investigate alterations in the remaining (intact) tendon
      mechanical properties at 4 and 8 weeks after injury. Twenty-four rats served as
      uninjured controls, whereas 72 were divided among 3 tendon detachment groups:
      supraspinatus tendon detachment, supraspinatus + infraspinatus tendon detachment,
      and supraspinatus + subscapularis tendon detachment. The remaining (intact)
      rotator cuff tendons had decreased mechanical properties in the presence of
      rotator cuff tears. The remaining (intact) subscapularis and infraspinatus tendon
      cross-sectional areas increased, whereas tendon modulus decreased after tears of
      both 1 and 2 tendons. The remaining (intact) tendon cross-sectional areas
      continued to increase with time after injury. These alterations could potentially
      lead to further tendon damage and tear progression.

PMID- 19095176
TI  - An analysis of four ulnar collateral ligament reconstruction procedures with
      cyclic valgus loading.
AB  - We describe a new transolecranon fossa ulnar (TOFU) collateral ligament
      reconstruction technique and compare its response to cyclic valgus loading with
      the Jobe, Docking, and DANE procedures. TOFU is an arthroscopically assisted,
      modified all-interference screw technique. A cyclic valgus moment was applied to
      32 intact and reconstructed, unembalmed elbows. Valgus angles were measured at 1,
      10, 100, and 1000 cycles. At all cycles, there was no difference between intact
      and TOFU-treated elbows. TOFU resulted in significantly smaller angles than DANE
      at cycles 10, 100, and 1000; Docking at cycle 1000; and Jobe at cycles 10, 100,
      and 1000. The TOFU procedure shows superior resistance to valgus loading than
      DANE and Jobe by cycle 10, and Docking by cycle 1000. Further study is needed to
      evaluate the clinical value of the TOFU procedure as an arthroscopically assisted
      technique.

PMID- 19095177
TI  - Pronation can increase the pressure on the posterior interosseous nerve under the
      arcade of Frohse: a possible mechanism of palsy after two-incision repair for
      distal biceps rupture--clinical experience and a cadaveric investigation.
AB  - Posterior interosseous nerve palsy is a recognized complication of 2-incision
      distal biceps tendon repair. We hypothesize that intraoperative forearm pronation
      can cause compression of the posterior interosseous nerve beneath the supinator
      and arcade of Frohse. Six human male cadaver upper extremities were dissected.
      Pressure on the posterior interosseous nerve beneath the arcade of Frohse and
      supinator was measured with a Swan-Ganz catheter connected to a pressure
      transducer. Pressure was significantly elevated in maximal pronation in all
      specimens with the elbow in both flexion and extension. Pressures at full
      pronation were significantly higher than pressures measured at 60 degrees of
      pronation (5 +/- 2 mm Hg in 60 degrees of pronation and 90 degrees of flexion, P
      < .0001; 7 +/- 3 mm Hg in 60 degrees of pronation and extension, P < 005).
      Maximal pronation can cause increased pressure on the posterior interosseous
      nerve. The safety of 2-incision distal biceps repair may be increased by avoiding
      prolonged, uninterrupted periods of hyperpronation.

PMID- 19095178
TI  - Biomechanics of open Bankart and coracoid abutment procedures in a human
      cadaveric shoulder model.
AB  - The specific aims of this experiment were (1) to develop a clinically relevant
      model of anteroinferior shoulder dislocation in the apprehension position to
      compare the biomechanics of the intact anterior capsuloligamentous structures,
      and (2) to evaluate the initial strength of an open Bankart and of a coracoid
      abutment procedure. Fifteen shoulders from deceased donors were used. For the
      intact shoulders, mean peak load was 486 N, and stiffness was 26,7 N/mm. For the
      Bankart repair, the mean peak load was 264 N, and mean stiffness was 14.1 N/mm.
      Transosseous repairs failed by suture pullout through soft tissues. For the
      coracoid abutment repair, the mean peak load was 607 N and stiffness was 25.57
      N/mm. This study reveals that the biomechanical performance of the Bankart and
      coracoid abutment repairs fails to reproduce the properties of the natural intact
      state.

PMID- 19095179
TI  - Health status as an important outcome factor after hemiarthroplasty.
AB  - The goal of this study was to determine functional results of hemiarthroplasty
      for 3- and 4-part proximal humeral fractures in elderly patients and to analyze
      factors affecting the outcome. Thirty-eight consecutive shoulders were treated
      with hemiarthroplasty after proximal humeral fracture. Two groups of patients
      with different health status were classified. Group I consisted of patients with
      2 or less comorbidities and a maximum of 2 medications at the time of injury.
      Patients in group II had 3 or more comorbidities with a minimum of 3 medications
      at the time of injury. The mean of the absolute Constant score in group I was 41,
      compared to 27 in group II (P < .05). Furthermore, compliance of the patient and
      regular physiotherapy proved to be important prognostic factors. If primary
      hemiarthroplasty is not likely to be successful with a low functional score, this
      surgical procedure should be reconsidered especially in patients with more than
      three comorbidities.

PMID- 19095180
TI  - Prognostic factors for unstable proximal humeral fractures treated with locking
      plate fixation.
AB  - This study evaluated the functional outcomes of proximal humeral fractures
      treated with locking plates and determined the prognostic factors for successful
      clinical outcomes. We included 44 patients with 45 unstable proximal humeral
      fractures. There were 19 two-part, 22 three-part, and 4 four-part fractures.
      Outcomes were analyzed by use of multivariate linear regression with several
      different combinations of 7 independent variables: age, fracture pattern,
      osteoporosis, calcium sulfate graft, rotator cuff suture loop, head-neck shaft
      angle, and comorbidity. The mean head-shaft angle was 132.4 degrees after the
      operation and decreased to 127.7 degrees at final follow-up. Five patients showed
      considerable loss of fixation. The analysis showed that delay in rehabilitation
      because of comorbidities and decreased head-neck shaft angle induced by lack of
      medial support were the primary prognostic factors that led to poor outcomes. The
      absence of comorbidity and the restoration of the medial metaphysis were the most
      reliable predictors of successful clinical outcomes.

PMID- 19095181
TI  - Methodological properties of six shoulder disability measures in patients with
      rheumatic diseases referred for shoulder surgery.
AB  - The aim of this study was to explore the methodological properties in 6 commonly
      used shoulder disability measures (Dash, Spadi, Oxford, the Constant score,
      Shoulder Function Assessment Scale, Bostrom's shoulder movement impairment scale)
      in patients with inflammatory or degenerative diseases referred for shoulder
      surgery. One-hundred and six patients completed the measures preoperatively.
      Fifty-five (51.9%) were not able to carry out the assessment of the strength
      component of the Constant score. Pearson correlation coefficients between the
      measures varied between 0.22 and 0.87. The lowest correlation coefficients were
      found between performance-based and self-report measures. All measures, except
      the Dash, were able to differentiate significantly between patients who were more
      and less severely affected. Performance-based measures differentiated better
      (effect size, 0.68- 0.87) than self-report measures (effect size, 0.21-0.61)
      between the 2 patient groups. Performance-based and self-report assessments
      provide complementary information about shoulder status and should not be used
      interchangeably.

PMID- 19095182
TI  - Total shoulder arthroplasty in patients with Parkinson's disease.
AB  - Currently, there is little information available on the results of total shoulder
      arthroplasty (TSA) in patients with Parkinson's disease. The purpose of the
      current study was to determine the results, risk factors for an unsatisfactory
      outcome, and rates of failure of TSA in patients with Parkinson's disease.
      Between 1978 and 2005, 49 total shoulder arthroplasties were performed in
      patients with Parkinson's disease for osteoarthritis of the shoulder. Forty-three
      shoulders (36 patients) were followed for a minimum of 2 years (mean, 8 years) or
      until the time of revision surgery. Total shoulder arthroplasty in patients with
      Parkinson's disease was associated with significant improvement in pain from 4.6
      to 1.8 (P < .001), external rotation from 21 degrees to 44 degrees (P < .001),
      and active abduction from 100 degrees to 119 degrees (P = .0489). There was no
      significant improvement in internal rotation (P = .09). There was no significant
      difference in outcome between males and females nor was there an association with
      stage of Parkinson's disease and outcome (P > .05). Eight shoulders underwent
      revision arthroplasty. Three of the 8 revisions were performed less than 1 year
      from the time of surgery due to instability. Total shoulder arthroplasty is
      associated with significant long-term improvement in pain, external rotation, and
      abduction in patients with Parkinson's disease. However, early postoperative
      instability appears to be higher in this patient population. The results of TSA
      in our patients with Parkinson's disease were marginal, with 20 (47%) achieving
      unsatisfactory results.

PMID- 19095183
TI  - Deep vein thrombosis after reconstructive shoulder arthroplasty: a prospective
      observational study.
AB  - This clinical study was performed to document the prevalence of deep vein
      thrombosis (DVT) after prosthetic shoulder replacement surgery. We prospectively
      followed 100 consecutive shoulder arthroplasty procedures (total shoulder
      replacement in 73 and hemiarthroplasty in 27) in 44 male and 56 female patients
      for 12 weeks (mean age, 67 years; range, 17-88 years). Risk factors for venous
      thromboembolic disease were assessed preoperatively and postoperatively. A 4-limb
      surveillance color flow Doppler ultrasound was performed at 2 days (100 patients)
      and 12 weeks (50 patients randomly selected) after surgery, and the presence and
      location of DVT were recorded. Postoperative symptomatic or fatal pulmonary
      emboli (PE) were also recorded. The overall prevalence of DVT was 13.0%,
      consisting of 13 DVTs in 12 patients. These included 6 ipsilateral and no
      contralateral upper extremity DVTs and 5 ipsilateral and 2 contralateral lower
      extremity DVTs. The prevalence of DVT was 10.0% (10/100) at day 2 after surgery
      and 6.0% (3/50) at week 12 after surgery. The incidence of symptomatic nonfatal
      PE was 2.0% (2/100), and that of fatal PE was 1.0% (1/100). Risk factors
      associated with venous thromboembolic disease did not reach statistical
      significance because of the small study population sample size. At our
      institution, the prevalence of DVT after reconstructive shoulder arthroplasty was
      13.0%, a rate comparable to that after hip arthroplasty (10.3%) but lower than
      that after knee arthroplasty (27.2%). Shoulder arthroplasty surgeons should be
      aware of the potential risk of perioperative thromboembolic complications in both
      the acute and subacute postoperative periods.

PMID- 19095184
TI  - Shoulder reconstruction in obstetric brachial plexus palsy in older children via
      a one-stage release and tendon transfers.
AB  - Shoulder contracture from obstetric palsy was surgically released in 24 older
      children, with simultaneous transfer of the latissimus dorsi and teres major
      tendons to the posterolateral humerus or rotator cuff. The mean age at surgery
      was 8 years 11 months. The children were evaluated at a mean follow-up time of 6
      years 8 months by the Modified American Shoulder and Elbow Surgeons Form and
      Shoulder Pain and Disability Index standardized shoulder assessment forms, a
      questionnaire assessing activities of daily living, and parent and patient
      satisfaction scales. The fixed internal rotation deformity of 30 degrees +/- 12
      degrees improved to 72.5 degrees +/- 27 degrees of external rotation.
      Improvements of 65 degrees +/- 26 degrees and 47 degrees +/- 33 degrees were seen
      in abduction and forward elevation, respectively, all without preoperative
      casting or manipulation. Increased external rotation had a more positive
      correlation with a higher functional score than abduction. Patients with lower
      preoperative functional scores had more rotational gain and higher functional
      scores after surgery. Those aged over 9 years had a functional gain similar to
      that of the younger children.

PMID- 19095185
TI  - Changes in shoulder muscle function with humeral position: a graphical
      description.
AB  - A graphical description of the change in the role played by each of the
      scapulohumeral muscles with respect to spatial joint position is presented.
      Moment arms were collected from a biomechanical model using the tendon travel
      method. Data cover elevation and flexion in a space between the frontal plane and
      a plane of elevation 60 degrees anterior to this. Segments of a given muscle were
      seen possibly to exhibit antagonistic moment components in relation to others,
      emphasizing the importance of muscle segmentation in biomechanical models.
      Graphical description of muscle function in conjunction with electromyographic
      studies enables a more complete assessment of active muscle function in relation
      to arm motion and position. In cases of attenuated muscular function, this also
      offers a means of detecting which muscle is involved and which other muscles
      possess compensating potential. Two examples illustrate the use of this data,
      particularly to clarify clinical issues.

PMID- 19095186
TI  - Cross-linked glenoid prosthesis: a wear comparison to conventional glenoid
      prosthesis with wear particulate analysis.
AB  - Wear debris has been observed in shoulder arthroplasties that use an ultrahigh
      molecular weight polyethylene (UHMWPE) glenoid component, and the biologic
      response to this debris contributes to aseptic loosening of the implant. The
      objective of this study was to assess the wear and particle morphology of a cross
      linked UHMWPE prosthetic glenoid. To our knowledge, this is the first time a
      simulator with kinematic considerations for assessing wear has been used in a
      shoulder model. Shoulder wear testing was conducted on 2 groups of glenoids (n =
      3 in each group) by use of an orthopaedic joint simulator to create worst-case
      scenario motions. One group was manufactured from conventional UHMWPE. The second
      was manufactured from 50-kGy cross-linked UHMWPE. The resulting wear rates for
      the conventional and cross-linked glenoid components were 46.7 +/- 2.6 mg/million
      cycles and 7.0 +/- 0.4 mg/million cycles, respectively. Particles isolated from
      the 2 groups showed similar morphologies; however, the calculated osteolytic
      potential of the cross-linked glenoid was significantly lower. The results of
      this study support the use of cross-linked UHMWPE glenoids in clinical
      applications.

PMID- 19095187
TI  - A day to remember leprosy.

PMID- 19095188
TI  - Drotrecogin alfa on trial.

PMID- 19095189
TI  - Household contact investigation of tuberculosis in low-income and middle-income
      countries: public-health impact.

PMID- 19095190
TI  - Efficacy and safety of cefepime.

PMID- 19095192
TI  - A strategic plan for Japanese encephalitis control by 2015.

PMID- 19095194
TI  - On the buses.

PMID- 19095195
TI  - Framework for the design and operation of high-level isolation units: consensus
      of the European Network of Infectious Diseases.
AB  - Patients with highly infectious diseases require safe, secure, high-quality
      medical care with high-level infection control, which may be most effectively
      delivered by specially trained staff in the setting of a high-level isolation
      unit (HLIU). The European Network of Infectious Diseases is a European Commission
      co-funded network of experts in the management of highly infectious diseases from
      national (or regional) centres designated for the care of this patient
      population. Participants took a consensus-based approach to develop a framework
      for the design and operation of HLIUs in Europe, covering clinical care
      provision, diagnostic services, transport, health and safety, and essential
      design and construction features, to support planning by health authorities for
      the safe and effective management of highly infectious diseases and preparedness
      for infectious disease emergencies in Europe.

PMID- 19095196
TI  - Interventions to reduce HIV transmission related to injecting drug use in prison.
AB  - The high prevalence of HIV infection and drug dependence among prisoners,
      combined with the sharing of injecting drug equipment, make prisons a high-risk
      environment for the transmission of HIV. Ultimately, this contributes to HIV
      epidemics in the communities to which prisoners return on their release. We
      reviewed the effectiveness of interventions to reduce injecting drug use risk
      behaviours and, consequently, HIV transmission in prisons. Many studies reported
      high levels of injecting drug use in prisons, and HIV transmission has been
      documented. There is increasing evidence of what prison systems can do to prevent
      HIV transmission related to injecting drug use. In particular, needle and syringe
      programmes and opioid substitution therapies have proven effective at reducing
      HIV risk behaviours in a wide range of prison environments, without resulting in
      negative consequences for the health of prison staff or prisoners. The
      introduction of these programmes in countries with an existing or emergent
      epidemic of HIV infection among injecting drug users is therefore warranted, as
      part of comprehensive programmes to address HIV in prisons.

PMID- 19095197
TI  - Errors in the approval process and post-marketing evaluation of drotrecogin alfa
      (activated) for the treatment of severe sepsis.
AB  - Regulatory agencies take responsibility for the safety and efficacy of the drugs
      they license. Over the past few years, however, several serious failings in the
      approval procedure have raised widespread concern that the present process of
      drug regulation is inadequate to guarantee the defence of public health. We
      discuss the approval process of drotrecogin alfa (activated), a non-antibacterial
      drug for the treatment of severe sepsis. The US Food and Drug Administration
      (FDA) and the European Medicines Agency (EMEA) approved drotrecogin alfa
      following a phase III trial that showed efficacy of the drug. However, on the
      basis of subgroup analyses, the drug was licensed only for use in part of the
      study population. This methodology is contrary to guidelines established by the
      FDA and EMEA themselves. According to these guidelines, analyses of non
      predefined subgroups do not provide sufficient evidence for drug approval.
      Although the results of several post-marketing trials raised doubts about the
      efficacy of drotrecogin alfa, both regulatory agencies passively accepted the
      reassuring interpretations of sponsored investigators and of the manufacturing
      company itself. The recent requirement of a confirmatory trial by the EMEA
      without recalling the drug from the market is the latest inconsistent step taken
      by the agency. The case of the approval and post-marketing evaluation of
      drotrecogin alfa, we believe, shows that the current drug regulation system needs
      reforming.

PMID- 19095199
TI  - Future directions in nephrolithiasis research.

PMID- 19095200
TI  - Economics and cost of care of stone disease.
AB  - Nephrolithiasis is associated with a high cost to society because of the high
      prevalence of disease and high recurrence rates. The total annual medical
      expenditures for urolithiasis in the United States were estimated at $2.1 billion
      in 2000. The cost of stone disease reflects the cost of health care services
      required to manage stone disease and the rate of utilization. Although the care
      of individuals with urolithiasis has shifted from the inpatient to the outpatient
      setting and the hospital length of stay has decreased, costs continue to rise
      because of increases in the prevalence of kidney stones. There are 2 potential
      areas that would allow for a decrease in stone disease-related costs, lower
      health care-related costs, and decreased prevalence of stone disease. Reducing
      treatment-related costs are unlikely to provide a solution to the high cost of
      caring for stone disease because physician-fee reductions did not result in a
      significant reduction in costs. Furthermore, there are no significant
      advancements in surgical technique or technologies in the horizon. One area of
      cost savings could be to develop better guidelines for acute management,
      optimizing timing for surgery in acute settings and increasing the practice of
      medical expulsive therapy. Another area with potential to reduce costs is the
      reduction of overall stone burden through the prevention of new stones or
      recurrences. Strategies for primary prevention in high-risk populations have not
      been studied and represent an area for future research. More efforts should be
      made to improve medical management of stone formers. These efforts include
      improving dietary recommendations, identifying barriers to evaluations and
      treatment of recurrent stone formers, improving patient compliance with
      recommendations, and development of new medications.

PMID- 19095201
TI  - Obesity and urolithiasis.
AB  - The current obesity epidemic in the United States has deleterious effects on the
      health of the population. Temporally related to the increase in obesity is an
      increase in the prevalence of urolithiasis. Epidemiologic studies have shown that
      the incident stone risk increases with body mass index. Obesity can increase
      stone risk in multiple ways. Excess nutritional intake increases traffic of
      lithogenic substances such as calcium, oxalate, and uric acid. Metabolic
      syndrome, commonly associated with obesity, alters renal acid-base metabolism,
      resulting in a lower urine pH and increased risk of uric acid stone disease. The
      low urine pH is caused by deficient ammonia production, which appears to be
      related to insulin resistance. Even weight-loss programs to combat obesity can
      influence stone risk. Contemporary bariatric surgery has been shown to frequently
      cause hyperoxaluria with associated stone formation and even oxalate nephropathy.
      Commonly used low-carbohydrate diets increase the risk of both calcium and uric
      acid stones. Certainly, the many health risks of obesity, including urolithiasis,
      necessitate weight loss, but recognition of the potential complications of such
      therapies is required to prevent induction of new and equally severe medical
      problems. The optimal approach to weight control that minimizes stone risk needs
      to be determined.

PMID- 19095202
TI  - Prospects for dietary therapy of recurrent nephrolithiasis.
AB  - The goal of this article is to propose a randomized controlled trial (RCT) that
      tests a hypothesis that dietary manipulation prevents recurrent kidney stones.
      Dietary interventions based on epidemiologic and pathophysiologic data are
      reviewed. The only diet trial successful in preventing stones showed that calcium
      intake of 1,200 mg/d, accompanied by restriction of animal protein, salt, and
      oxalate ingestion, was superior to 400 mg of calcium and restricted oxalate
      intake. This study may be worth repeating in women and in a society in which salt
      restriction might be less effective (eg, United States). The net result of diet
      trials establishes significant positive effects on urine chemistries, but these
      have not yet shown efficacy with regard to stone recurrence. Oxalate restriction
      alone could be effective, but many questions regarding which populations to study
      are not defined, and dietary oxalate's contribution to stone formation is
      disputed. Would such a study be limited to patients identified as having high
      dietary oxalate intake or high intestinal oxalate absorption? Would colonization
      with Oxalobacter formigenes influence the result? The increased prevalence of
      stones is linked to weight gain and obesity, making weight loss a possible
      therapy to prevent stones. Randomized trials show that diets consisting of low
      fat content or low-caloric content cause modest weight loss and might be
      effective in reducing stone formation. Because the efficacy of thiazides in the
      prevention of stones in patients with hypercalciuria is clear, I propose dietary
      comparison of higher calcium intake to thiazides for the prevention of calcium
      based kidney stones.

PMID- 19095204
TI  - Imaging in diagnosis, treatment, and follow-up of stone patients.
AB  - Imaging has an essential role in the diagnosis, management, and follow-up of
      patients with stone disease. A variety of imaging modalities are available to the
      practicing urologist, including conventional radiography (KUB), intravenous
      urography (IVU), ultrasound (US), magnetic resonance urography, and computed
      tomography (CT) scans, each with its advantages and limitations. Traditionally,
      IVU was considered the gold standard for diagnosing renal calculi, but this
      modality has largely been replaced by unenhanced spiral CT scans at most centers.
      Renal US is recommended as the initial imaging modality for suspected renal colic
      in pregnant women and children, but recent literature suggests that a low-dose CT
      scan may be safe in pregnancy. Intraoperative imaging by fluoroscopy or US plays
      a large part in assisting the urologist with the surgical intervention chosen for
      the individual stone patient. Posttreatment imaging of stone patients is
      recommended to ensure complete fragmentation and stone clearance. Plain
      radiography is suggested for the follow-up of radiopaque stones, with ultrasound
      and limited IVU reserved for the follow-up of radiolucent stones to minimize
      cumulative radiation exposure from repeated CT scans. Patients with asymptomatic
      calyceal stones who prefer an observational approach should have a yearly KUB to
      monitor progression of stone burden. Current research has been aimed toward the
      development of a micro-CT scan and coherent-scatter analysis to determine stone
      composition in vivo. This may have a significant impact on the future clinical
      management of renal calculi by facilitating selection of the most appropriate
      surgical intervention based on stone composition at the time of presentation.

PMID- 19095205
TI  - Radiology of urolithiasis: implications of radiation exposure and new imaging
      modalities.
AB  - Computed tomography (CT) scanning is now the standard imaging technique for
      detecting and characterizing urolithiasis. However, the potential effects of the
      radiation exposure from CT examinations have raised concern among some
      physicians. This article describes the radiation doses for various urolithiasis
      imaging techniques and describes techniques to optimize and reduce radiation
      exposures to patients undergoing these examinations. Potential future directions
      in radiologic techniques used for studying urolithiasis are also discussed.

PMID- 19095203
TI  - Pharmacology of stone disease.
AB  - Kidney stone disease remains a major health and economic burden on the nation. It
      has been increasingly recognized that nephrolithiasis can be both a chronic or
      systemic illness. There have been major limitations in the development of new
      drugs for the prevention and management of this disease, largely due to our lack
      of understanding of the complex pathophysiologic mechanisms involving the
      interaction of three major target organs: the kidney, bone, and intestine. We
      also do not yet understand the molecular genetic basis of this polygenic
      disorder. These limitations are coupled with the incorrect perception that kidney
      stone disease is solely an acute illness, and the lack of reliable tests to
      assess outcome measures. All of these factors combined have diminished the
      willingness of the pharmaceutical industry to engage in the development of novel
      drugs.

PMID- 19095206
TI  - Adjuvant therapy after surgical stone management.
AB  - The aim of this article was to review the most widely researched adjuvant medical
      therapies for the surgical management of urolithiasis. Articles were identified
      and reviewed from PubMed and Medline databases with MeSH headings focusing on the
      various surgical treatments of urolithiasis and adjuvant therapy. Additional
      articles were retrieved from references and conference proceedings. Surgical
      treatments reviewed included shockwave lithotripsy, ureteroscopy, and
      percutaneous nephrolithotomy. Adjuvant therapy was considered medical or
      complementary therapy as an adjunct to these surgical interventions. Adjuvant
      therapy for the surgical management of urolithiasis has been documented to
      increase stone-free rates, reduce stone remission rates, prevent renal damage,
      and decrease postoperative morbidity. A variety of agents have been studied,
      ranging from antioxidants to alpha-blockers and to alkalinizing agents.
      Additionally, there is increasing interest in complementary adjuvant therapy (ie,
      acupuncture). Adjuvant therapy is a fertile area for research in the surgical
      management of urolithiasis. The optimal agents have yet to be determined and
      therefore further investigation is warranted and necessary.

PMID- 19095208
TI  - Clinical trials of the surgical management of urolithiasis: current status and
      future needs.
AB  - We reviewed the literature on the surgical treatment of urolithiasis. All
      prospective, randomized trials on the surgical treatment of stone disease were
      reviewed. Percutaneous nephrolithotomy (PNL) is superior to shockwave lithotripsy
      (SWL) or open surgery in the treatment of staghorn calculi. For ureteral stones,
      ureteroscopy appears to result in a higher stone-free rate and lower need for
      retreatment compared with SWL but has a higher complication rate and increased
      hospital stay. For lower pole renal calculi, PNL results in a higher stone-free
      rate and lower need for retreatment compared with SWL but has a higher
      complication rate and increased hospital stay. Most areas of surgical stone
      treatment have been addressed by a randomized controlled trial; however, most
      trials were of poor quality. Trials tend to focus only on radiologic outcomes. No
      study to date has been able to show a measurable quality of life benefit to
      patients, possibly because no condition-specific quality of life instruments have
      been developed. In addition, economic impact, both direct and indirect, has been
      rarely characterized. The surgical treatment of kidney stones is poorly
      researched. Future trials should be performed with adequate funding and patient
      focused outcomes.

PMID- 19095207
TI  - Surgical management of stones: new technology.
AB  - In recent years, the surgical treatment of kidney stone disease has undergone
      tremendous advances, many of which were possible only as a result of improvements
      in surgical technology. Rigid intracorporeal lithotrites, the mainstay of
      percutaneous nephrolithotomy, are now available as combination ultrasonic and
      ballistic devices. These combination devices have been reported to clear a stone
      burden with much greater efficiency than devices that operate by either
      ultrasonic or ballistic energy alone. The laser is the most commonly used
      flexible lithotrite; advances in laser lithotripsy have led to improvements in
      the currently utilized Holmium laser platform, as well as the development of
      novel laser platforms such as Thulium and Erbium devices. Our understanding of
      shock wave lithotripsy (SWL) has been improved over recent years as a consequence
      of basic science investigations. It is now recognized that there are certain
      maneuvers with SWL that the treating physician can do that will increase the
      likelihood of a successful outcome while minimizing the likelihood of adverse
      treatment-related events.

PMID- 19095209
TI  - Salvage of cartilage framework exposure in microtia reconstruction using a
      mastoid fascial flap.
AB  - One of the common complications of microtia reconstruction with cartilage
      grafting is exposure of the framework. Recently, we used a mastoid fascial flap
      for salvage operations in two microtia patients, who had partial skin necrosis
      with resultant exposure of the cartilage framework. Following the excision of the
      necrotic skin, the anteriorly based mastoid fascial flap was elevated and
      transferred as a hinge flap on to the portion of the exposed framework. Split
      thickness skin grafts were applied over the mastoid fascial flap. Each skin graft
      took well and the relief of the reconstructed ear was preserved in both cases.
      This salvage method has a large advantage of not leaving any visible scars on the
      temporal region and the reliability of its rich blood supply.

PMID- 19095210
TI  - Pancreatoduodenectomy using a no-touch isolation technique.
AB  - BACKGROUND: Pancreatoduodenectomy is the only effective treatment for cancers of
      the periampullary region. Because surgeons usually grasp tumors during
      pancreatoduodenectomy, this procedure may increase the risk of squeezing and
      shedding the cancer cells into the portal vein, retroperitoneum, and/or
      peritoneal cavity. In an effort to overcome these problems, we have developed a
      surgical technique for no-touch pancreatoduodenectomy. METHODS: From March 2005
      through May 2008, 42 patients have been operated on following this technique.
      Resected margins were microscopically analyzed. RESULTS: We describe a technique
      for pancreatoduodenectomy using a no-touch isolation technique. We resect cancers
      with wrapping them within Gerota's fascia and transect the retroperitoneal margin
      along the right surface of the superior mesenteric artery and abdominal aorta
      without grasping tumors. CONCLUSIONS: No-touch pancreatoduodenectomy has many
      potential advantages that merit further investigation in future randomized
      controlled trials.

PMID- 19095211
TI  - Hemolysis falsely decreases intraoperative parathyroid hormone levels.
AB  - BACKGROUND: Intraoperative parathyroid hormone (IOPTH) measurement is used to
      confirm biochemical cure during parathyroidectomy. Falsely decreased IOPTH
      measurements could result in false-negative or false-positive results and lead to
      failed parathyroidectomy or unnecessary additional exploration. STUDY DESIGN: The
      records of all patients who underwent parathyroidectomy with IOPTH between May
      and August 2007 were retrospectively reviewed, and the frequency of hemolysis of
      IOPTH samples was determined. Separately, 10 split-samples were hemolyzed using
      the freeze-thaw technique. RESULTS: Forty-seven patients underwent
      parathyroidectomy, and 226 IOPTH samples were sent. Seventeen (7.5%) specimens
      from 9 (18.8%) patients were hemolyzed. In 8 split-samples, the range of decrease
      caused by hemolysis was 24.5% to 53.8% compared with nonhemolyzed controls.
      CONCLUSIONS: Hemolysis of IOPTH samples occurs commonly and falsely decreases
      IOPTH levels. Unrecognized hemolysis in pre-excision specimens could result in
      false-negative IOPTH results and lead to unnecessary continued exploration.
      Unrecognized hemolysis in postexcision specimens could lead to false-positive
      IOPTH results and lead to failed parathyroidectomy and the need for reoperation.
      Thus, hemolysis may be an easily preventable cause of erroneous IOPTH
      measurements.

PMID- 19095212
TI  - Prevention of wound healing disorders and recurrence.

PMID- 19095213
TI  - Telavancin versus vancomycin for the treatment of complicated skin and skin
      structure infections associated with surgical procedures.
AB  - BACKGROUND: We compared telavancin with vancomycin for the treatment of
      complicated skin and skin-structure infections (cSSSI) caused by Gram-positive
      bacteria. METHODS: This was a retrospective analysis of clinical and
      microbiologic efficacy assessed at test-of-cure (7 to 14 days after completing
      therapy) in 194 patients from 2 randomized, double-blind clinical trials
      comparing telavancin (10 mg/kg intravenous [IV] every 24 hours; n = 101) with
      vancomycin (1 g IV every 12 hours; n = 93) for the treatment of cSSSI. RESULTS:
      Baseline characteristics were similar for both treatment groups. Clinical cure
      and microbiologic eradication rates demonstrated consistent trends favoring
      telavancin over vancomycin; however, the differences were not statistically
      significant. The incidence of adverse events was mostly similar between groups.
      CONCLUSIONS: The efficacy of telavancin was at least equivalent to that of
      vancomycin for the treatment of cSSSI. These data suggest that telavancin may be
      a useful alternative for treatment of cSSSI caused by S. aureus, particularly
      MRSA.

PMID- 19095214
TI  - International medical graduates in surgery: facing challenges and breaking
      stereotypes.

PMID- 19095215
TI  - Accurate axillary lymph node dissection is feasible after neoadjuvant
      chemotherapy.
AB  - BACKGROUND: Recently, lower axillary lymph node retrieval after neoadjuvant
      chemotherapy was reported. We did not have this experience, and retrospectively
      analyzed our axillary lymph node dissections (ALNDs). METHODS: One hundred ninety
      one patients who had ALND after neoadjuvant chemotherapy were compared with 192
      patients with primary ALND after a positive sentinel node biopsy. RESULTS: There
      were no differences in the mean number of nodes retrieved between the neoadjuvant
      group and the primary surgery group: 16.3 (range 4-38) and 15.8 (range 6-33),
      respectively (P = .4); or in the retrieval of fewer than 10 lymph nodes: 13/191
      (7%) and 11/192 (6%) (P = .7). The number of cases with retrieval of more than 20
      lymph nodes was higher in the neoadjuvant group: 42/191 (22%) versus 26/192 (13%)
      (P = .03). In the neoadjuvant group, 150/191 (79%) patients had residual lymph
      node metastasis after neoadjuvant chemotherapy. CONCLUSION: Our results show the
      feasibility and need to remove enough lymph nodes to provide precise prognostic
      information and adequate local control.

PMID- 19095216
TI  - Collagen in the transversalis fascia of patients with indirect inguinal hernia: a
      case-control study.
AB  - BACKGROUND: The aim of this study was to analyze the constituents of total and
      types I and III collagen fibers in the transversalis fascias of patients with
      indirect inguinal hernias, compared with samples removed from nonherniated
      cadavers. METHODS: Biopsy samples from 26 patients and 26 cadavers were analyzed.
      Hematoxylin-eosin and picrosirius staining techniques were used. The images
      obtained were analyzed using a video morphometric technique to determine the
      constituents of total collagen and types I and III collagen in the transversalis
      fascia. The picrosirius-stained tissues were submitted to observation under
      polarized-light microscopy. RESULTS: The results showed 17.3% less total collagen
      in patients with hernias compared with the control group (P < .01). Type I
      collagen in patients with indirect inguinal hernias was 23.7% less than the
      control group (P < .01), type III collagen was 6.4% less in the controls (P <
      .01). CONCLUSION: The lower percentages of total collagen and type I collagen in
      the transversalis fascias of patients with indirect inguinal hernias could be a
      factor in hernia formation.

PMID- 19095217
TI  - [Adherence to national guidelines for lipid management in a department of
      endocrinology].
AB  - OBJECTIVES: National guidelines for lipid management have been updated in March
      2005 by the French Health Products Safety Agency (Afssaps). The objective of this
      study was to assess clinical practices based on these recommendations in a
      department of endocrinology specialized in the management of dyslipidemic
      patients. MATERIALS AND METHODS: A sample of patients was independently selected
      among those referred to our outpatient clinic for assessment of hyperlipidemia.
      We analyzed retrospectively whether the management of dyslipidemia in these
      patients was consistent with national guidelines. RESULTS: We included 62
      patients. At admission, 61% of patients had a lipid-lowering treatment that was
      consistent with the guidelines and a LDL-cholesterol value below the target
      level. At discharge, the lipid-lowering treatment was modified in 27% of
      patients. The changes were consistent with Afssaps guidelines in 79% of patients.
      Cases of non-compliance with the guidelines were explained by a lower threshold
      of LDL-cholesterol target in patients with carotid plaques and no changes because
      LDL-cholesterol was just above the LDL-cholesterol target. CONCLUSION: Lipid
      management was consistent with Afssaps guidelines in a majority of patients.
      However, this study emphasized unresolved problems in lipid management, such as
      the question of integrating arterial status in the therapeutic decision.

PMID- 19095218
TI  - Lesions in the associative striatum improve obsessive-compulsive disorder.

PMID- 19095219
TI  - Variation in catechol-O-methyltransferase is associated with duloxetine response
      in a clinical trial for major depressive disorder.
AB  - BACKGROUND: The study objective was to evaluate variations in genes implicated in
      antidepressant mechanism of action for association with response to duloxetine
      treatment in major depressive disorder (MDD). METHODS: We assessed response over
      6 weeks in 250 duloxetine-treated Caucasian patients in a randomized, double
      blind study of patients with MDD. Single nucleotide polymorphisms (SNPs) were
      genotyped in 19 candidate genes selected based on evidence for involvement in
      antidepressant mechanism of action. Primary analysis examined baseline to end
      point reduction in the 17-item Hamilton Depression Rating Scale (HAMD17) total
      score, using a set-based test for association for each gene. Follow-up analyses
      examined individual SNPs within any significant gene for association with
      reduction in HAMD17 and 30-item Inventory of Depressive Symptomatology-Clinician
      Rated (IDS-C-30). RESULTS: After correction for multiple comparisons, only COMT
      was associated with change in HAMD17 (experiment wide p = .018). Peak association
      was detected with rs165599 (p = .006), which accounted for approximately 3% of
      variance in HAMD17 change and >4% of variance in IDS-C-30 change (p = .001). The
      least-squared mean change (SE) in HAMD17 score by rs165599 genotype was -10.8
      (1.2), -8.7 (.6), and -6.5 (.7) for patients with GG, GA, and AA genotypes,
      respectively. For SNPs in serotonin 2A receptor (HTR2A) previously associated
      with citalopram response, including rs7997012, no significant evidence of
      association with duloxetine response was identified. CONCLUSIONS: Single
      nucleotide polymorphisms in COMT were associated with symptom change in
      duloxetine-treated patients with MDD. If replicated, the magnitude of the COMT
      genotype effect is of clinical relevance.

PMID- 19095220
TI  - Baseline expression of alpha4beta2* nicotinic acetylcholine receptors predicts
      motivation to self-administer nicotine.
AB  - BACKGROUND: Marked interindividual differences in vulnerability to nicotine
      dependence exist, but factors underlying such differences are not well
      understood. The midbrain alpha4beta2* subtype of nicotinic acetylcholine
      receptors (nAChRs) has been implicated in mediation of the reinforcing effects of
      nicotine responsible for dependence. However, no study has been performed
      evaluating the impact of interindividual differences in midbrain nAChR levels on
      motivation to self-administer nicotine. METHODS: Baseline levels of alpha4beta2*
      nAChRs were measured using 2-[(18)F]fluoro-A-85380 (2-FA) and positron emission
      tomography (PET) in five squirrel monkeys. Motivation to self-administer nicotine
      (number of lever presses) was subsequently measured using a progressive-ratio
      (PR) schedule of reinforcement. RESULTS: Greater motivation to self-administer
      nicotine was associated with lower levels of midbrain nAChRs. CONCLUSIONS: The
      results suggest that level of expression of nAChRs is a contributing factor in
      the development of nicotine dependence. Similarly, it has been previously shown
      that low levels of dopamine D(2) receptors (DRD2) are associated with a higher
      preference for psychostimulant use in humans and nonhuman primates. Together,
      results from these PET studies of dopaminergic and nicotinic cholinergic
      transmission suggest that an inverse relationship between the availability of
      receptors that mediate reinforcement and the motivation to take drugs exists
      across different neurotransmitter systems.

PMID- 19095221
TI  - The role of the galaninergic system in modulating stress-related responses in an
      animal model of posttraumatic stress disorder.
AB  - BACKGROUND: Converging evidence implicates the regulatory neuropeptide galanin in
      anxiety- and depression-related behaviors, through modulation of neuroendocrine,
      serotonergic, and noradrenergic systems. This study examined the relationship
      between stress-induced posttraumatic stress disorder (PTSD)-like behavioral
      response patterns in rats and galanin mRNA levels in key brain areas and the
      effects of acute phase pharmacologic manipulation using an agonist (galnon) on
      behavioral, physiologic, and response patterns of brain-derived neurotrophic
      factor (BDNF) and 5-hydroxytryptamine-1A (5HT-1A). METHOD: Galanin mRNA
      expression was assessed in the frontal cortex and hippocampus in the short- and
      long-term (30 min and 7 days) after exposure to predator scent stress. The
      effects of intraperitoneal galnon .5 mg/kg versus saline 1 hour postexposure on
      behavioral tests (elevated plus maze and acoustic startle response) were
      evaluated 7 days later. Trauma-cue response, circulating corticosterone, and
      localized brain expression of 5HT-1A receptors and BDNF were subsequently
      assessed. All data were analyzed in relation to individual behavior patterns.
      RESULTS: Whereas animals with minimal behavioral disruption displayed a lasting
      upregulation of galanin mRNA in the hippocampal CA1 area, those with extreme
      behavioral responses displayed downregulation in both CA1 and frontal cortex.
      Immediate postexposure treatment with galnon significantly reduced prevalence
      rates of extreme responders, reduced trauma-cue freezing responses, corrected the
      corticosterone response, and increased CA1 expression of 5HT-1A and BDNF mRNA
      compared with saline controls. CONCLUSIONS: Galanin is actively involved in the
      neurobiological response to predator scent stress with resilience/recovery after
      stress exposure and thus warrants further study as a potential therapeutic avenue
      for the treatment of anxiety-related disorders.

PMID- 19095223
TI  - Spontaneous mapping of number and space in adults and young children.
AB  - Mature representations of space and number are connected to one another in ways
      suggestive of a 'mental number line', but this mapping could either be a cultural
      construction or a reflection of a more fundamental link between the domains of
      number and geometry. Using a manual bisection paradigm, we tested for number line
      representations in adults, young school children, and preschool children. Non
      symbolic numerical displays systematically distorted localization of the midpoint
      of a horizontal line at all three ages. Numerical and spatial representations
      therefore are linked prior to the onset of formal instruction, in a manner that
      suggests a privileged relation between spatial and numerical cognition.

PMID- 19095224
TI  - Explanation and categorization: how "why?" informs "what?".
AB  - Recent theoretical and empirical work suggests that explanation and
      categorization are intimately related. This paper explores the hypothesis that
      explanations can help structure conceptual representations, and thereby influence
      the relative importance of features in categorization decisions. In particular,
      features may be differentially important depending on the role they play in
      explaining other features or aspects of category membership. Two experiments
      manipulate whether a feature is explained mechanistically, by appeal to proximate
      causes, or functionally, by appeal to a function or goal. Explanation type has a
      significant impact on the relative importance of features in subsequent
      categorization judgments, with functional explanations reversing previously
      documented effects of 'causal status'. The findings suggest that a feature's
      explanatory importance can impact categorization, and that explanatory
      relationships, in addition to causal relationships, are critical to understanding
      conceptual representation.

PMID- 19095222
TI  - A line of mice selected for high blood ethanol concentrations shows drinking in
      the dark to intoxication.
AB  - BACKGROUND: Many animal models of alcoholism have targeted aspects of excessive
      alcohol intake (abuse) and dependence. In the rodent, models aimed at increasing
      alcohol self-administration have used genetic or environmental manipulations, or
      their combination. Strictly genetic manipulations (e.g., comparison of inbred
      strains or targeted mutants, selective breeding) have not yielded rat or mouse
      genotypes that will regularly and voluntarily drink alcohol to the point of
      intoxication. Although some behavioral manipulations (e.g., scheduling or
      limiting access to alcohol, adding a sweetener) will induce mice or rats to drink
      enough alcohol to become intoxicated, these typically require significant food or
      water restriction or a long time to develop. We report progress toward the
      development of a new genetic animal model for high levels of alcohol drinking.
      METHODS: High Drinking in the Dark (HDID-1) mice have been selectively bred for
      high blood ethanol concentrations (BEC, ideally exceeding 100 mg%) resulting from
      the ingestion of a 20% alcohol solution. RESULTS: After 11 generations of
      selection, more than 56% of the population now exceeds this BEC after a 4-hour
      drinking session in which a single bottle containing 20% ethanol is available.
      The dose of ethanol consumed also produced quantifiable signs of intoxication.
      CONCLUSIONS: These mice will be useful for mechanistic studies of the biological
      and genetic contributions to excessive drinking.

PMID- 19095225
TI  - Dr. Strangelove syndrome.

PMID- 19095226
TI  - Parkinson's disease: the syndrome, the pathogenesis and pathophysiology.
AB  - Parkinson's disease (PD) is characterised by a slowly expanding degeneration of
      neurons particularly in the mesencephalon. The causes are unknown although risk
      factors in the genetic and toxic domain are being discovered. An important
      pathophysiological feature in PD is the loss of part of the dopaminergic neurons
      in the substantia nigra (SN) resulting in a specific dysorganisation of the
      complicated basal ganglia (BG) circuits. The relay functions at the level of the
      striatum e.g., are out of balance leading to disturbed subcortico-cortical
      interactions. At a functional level this is shown by timing and scaling problems
      when performing movements and clinically this translates into initiation
      problems, bradykinesia and others. Dysarthria can of course be an important
      problem. However, how these basic disturbances of motor organisation can be
      copied into the cognitive domain (in terms of disturbed "mental movements") is a
      topic under discussion. It remains to be seen whether the basic pathophysiology
      of PD has consequences for the specific language organisation by the brain or
      whether language problems are merely secondary to the overall "mental motor
      slowing". Here an overview of the pathogenesis, basic pathophysiology and
      clinical problems of PD will be given.

PMID- 19095227
TI  - Hartline's Limulus.

PMID- 19095229
TI  - Feature detectors.

PMID- 19095230
TI  - Recovery from hemineglect: differential neurobiological effects of optokinetic
      stimulation and alertness training.
AB  - We prospectively investigated by means of neuropsychological tests and functional
      magnetic resonance imaging (fMRI) the behavioural and neural effects of a 3-week
      optokinetic stimulation (OKS) training in 7 patients with chronic visuospatial
      neglect resulting from right-hemisphere lesions. Behaviourally, OKS caused both a
      short- and a long-term (4 weeks) improvement of performance in a neglect test
      battery (compared to a 3-week baseline period). This amelioration of neglect
      symptoms was associated with increases of neural activity during an fMRI spatial
      attention task bilaterally in the middle frontal gyrus and the precuneus.
      Additional left hemisphere increases in neural activity were observed in the
      cingulate gyrus, angular gyrus, middle temporal gyrus and occipital cortex. This
      pattern of activation represents a combination of areas normally involved in
      spatial attention plus a compensatory recruitment of left hemisphere areas. These
      results were then compared with data from our previous study (Thimm et al., 2006)
      which employed an alertness training (AIXTENT) with an otherwise identical
      treatment study design. After the OKS training there was more activation
      bilaterally in the precuneus than after the AIXTENT training. In contrast, after
      AIXTENT training there was more activation bilaterally in frontal cortex. Taken
      together, the results show that amelioration of neglect can be induced by both
      OKS and alertness training. The data furthermore suggest that the differential
      activations of frontal or parietal areas may reflect the specific impact of the
      two types of training either on an anterior system for the control of attention
      intensity (AIXTENT) or on the posterior system of spatial attention (OKS).

PMID- 19095231
TI  - The rhythmic brain.

PMID- 19095232
TI  - Potential for infection in orthopaedic practice due to individually packaged
      screws.
AB  - The use of implants is widespread in orthopaedic practice. In recent times screws
      and plates have increasingly been supplied individually pre-packaged. We
      hypothesised that there is a potential for an increased risk of infection
      associated with the practice of using individually packaged screws. In this study
      an attempt was made to recreate as closely as possible the standard practice of
      opening screw packets in the operating theatre. The exterior of 50 screw packets
      was cultured. The outer screw packets were then opened over a draped instrument
      table above a petri dish. As a control, petri dishes were left open to the air in
      the same theatre environment. The packet exteriors grew cultures of organisms in
      24/50 cases. The act of opening the packets yielded a growth in 7/50 cases. There
      was no growth on the control petri dishes. The significance of the result and
      potential solutions are discussed.

PMID- 19095233
TI  - Outcome and complications of posterior transiliac plating for vertically unstable
      sacral fractures.
AB  - Vertically unstable sacral fractures often make it difficult to achieve rigid
      fixation and there is no consensus on the optimal fixation technique for these
      injuries. The purpose of this study was to evaluate complication rate and short
      term outcome of vertically unstable sacral fractures treated by posterior
      transiliac plate fixation. We performed a retrospective review of prospectively
      collected data of patients who underwent posterior transiliac plating for sacral
      fractures at two institutions. All patients were treated with the standard
      posterior approach using a 4.5-mm reconstruction plate and followed for at least
      12 months. Patients' demographics, Majeed functional questionnaire surveys, and
      radiographic outcomes were collected. There were 19 patients with a mean age of
      37.5-years. The mean follow-up was 26.3 months. The most frequent mechanism of
      injury was a fall from a height. According to the AO/OTA classification, there
      were 10 C1, 6 C2, and 3 C3, which were classified as 2 Denis I, 20 Denis II, and
      2 Denis III, including 5 bilateral sacral fractures. Neurological deficit at the
      initial examination was recorded in 10 patients. The mean ISS was 20.7 and the
      mean timing of the internal fixation was 6.4 days. Anterior internal fixation of
      pelvic ring was added in eight patients. A Morel-Lavallee lesion was identified
      in 5 patients during the operation. Reductions were graded as nine excellent,
      seven good, and three fair according to the method of Tornetta. There were two
      postoperative surgical wound infections, both occurring in patients with a Morel
      Lavallee lesion. All the sacral fractures united eventually and no implant
      failure occurred, though there were two patients with a small loss of reduction
      (<5mm) over the follow-up period. A total of 18 patients completed the functional
      assessment with a mean score of 78.5 points. Posterior plate fixation of
      vertically unstable sacral fractures is effective in maintaining fracture
      reduction even in the presence of significant posterior comminution. We caution
      its use in the presence of a known Morel-Lavallee lesion, as this may increase
      the wound complication and infection risk.

PMID- 19095234
TI  - The magnification of digital radiographs in the trauma patient: implications for
      templating.
AB  - INTRODUCTION: Digital radiographs are increasingly used for planning orthopaedic
      surgical procedures, despite the fact that they are frequently not calibrated to
      correct for magnification. The typical magnification of digital radiographs in
      the trauma patient has not yet been reported. The aims of this study were to
      assess the magnification of such radiographs, and to discuss if and when accurate
      calibration is required for trauma templating. MATERIALS AND METHODS: The
      operative notes and postoperative radiographs of 227 trauma patients were
      obtained. Each patient had undergone one of the following procedures: hip
      hemiarthroplasty, femoral nailing, tibial nailing, ankle plating, humeral
      nailing, humeral plating, or forearm plating. The dimensions of the implants used
      were measured on the uncalibrated postoperative radiographs using the hospital's
      Picture Archiving and Communication System software. The actual dimensions of the
      orthopaedic implants were obtained from the operation notes, and these were
      compared with the radiographic measurements. The intraobserver and interobserver
      variability of the radiographic measurements was also assessed. RESULTS: The
      radiographic magnification was greatest for the femoral head, and most variable
      for the femoral shaft. The magnification was least for the forearm. In general
      the magnitude and variability of magnification was least at the peripheries.
      There was good correlation between the measured and actual dimensions of the
      implants. The intraobserver and interobserver variability between the
      radiographic measurements was extremely small. CONCLUSION: Despite the ease and
      convenience of performing measurements on digital radiographs, these measurements
      are unreliable if the radiograph has not been calibrated. We believe that careful
      calibration of digital radiographs is essential for accurate templating in the
      trauma patient, although is less critical when templating the humeral canal, the
      tibial canal, the ankle and the forearm.

PMID- 19095235
TI  - Comprehensive evaluation of coronary arteries by multidetector-row cardiac
      computed tomography according to the glucose level of asymptomatic individuals.
AB  - BACKGROUND: Early detection of atherosclerosis in individuals with diabetes is
      important because of high cardiovascular mortality in this population. We
      performed multidetector-row computed tomography (MDCT) in asymptomatic
      individuals to investigate the status of coronary artery stenosis and plaque
      characteristics depending on the glucose level. METHODS AND RESULTS: The plaque
      burden (number of diseased coronary segments), severity of stenosis, plaques
      characteristics, and coronary artery calcium score (CACS) were assessed by MDCT
      in 1043 asymptomatic individuals. Anthropometric parameters and metabolic
      profiles were also acquired. Twenty-one percents of subjects had plaques and 5%
      had significant stenosis. Mean (+/-S.D.) CACS of study population was 17+/-81.
      Subjects with impaired fasting glucose (IFG, n=215, 21%) or diabetes (n=112, 11%)
      had a greater plaque burden, more coronary stenosis (>50% of diameter stenosis)
      and higher CACS than normal subjects (all, p<0.01). Noncalcified and mixed
      plaques were observed more in subjects with diabetes (19%) and IFG (11%) than
      normal (7%). After adjustment for confounding factors, higher fasting glucose was
      strongly associated with significant coronary stenosis and a greater plaque
      burden. CONCLUSIONS: More significant coronary stenosis and multivessel
      involvement, higher CACS, and greater plaque burden were observed in subjects
      with IFG or diabetes by MDCT, even they are asymptomatic. Proactive screening,
      irrespective of the imaging modalities used, in asymptomatic subjects with
      prediabetes and diabetes is helpful to identify those who have a higher
      cardiovascular morbidity and mortality. Further studies will guide us with
      respect to which imaging modality is more appropriate.

PMID- 19095236
TI  - Understanding the importance of the viscosity contrast between the sample solvent
      plug and the mobile phase and its potential consequence in two-dimensional high
      performance liquid chromatography.
AB  - The effect of solvent viscosity mismatch on elution performance in reversed-phase
      HPLC was studied using moment analysis. Two conditions were tested: (1) the
      mobile phase viscosity was less than the injection plug viscosity, and (2) the
      mobile phase viscosity was greater than the injection plug viscosity. Under the
      first condition, retention time and elution performance decreased as the
      viscosity contrast between the mobile phase and injection plug increased. The
      effect on performance was more marked as the injection volume increased. A
      decrease in performance of 12% for compounds with retention factors up to 2.8 was
      apparent even when the viscosity contrast was only 0.165 cP. In the second set of
      conditions, elution performance was actually observed to increase, by as much as
      25% for a 40 microL injection, as the viscosity contrast between the mobile phase
      and the solute plug increased. No change in the retention factor was observed.
      This behaviour was attributed to the shape of an injection plug as it enters into
      the column, whereby a low viscosity plug permeates away from the wall when the
      column contains a higher viscosity mobile phase, and vice a versa for a high
      viscosity plug entering a low viscosity mobile phase. At no stage was either a
      band splitting or shoulders observed with viscosity contrasts up to 1.283 cP, as
      could have been expected.

PMID- 19095237
TI  - Simple assay for monitoring seven quinolone antibacterials in eggs: extraction
      with hot water and liquid chromatography coupled to tandem mass spectrometry.
      Laboratory validation in line with the European Union Commission Decision
      657/2002/EC.
AB  - A simple and rapid method able to determine residues of seven quinolone
      antibacterials in whole eggs is presented here. This method is based on the
      matrix solid-phase dispersion technique with hot water as extractant followed by
      liquid chromatography-tandem mass spectrometry. After depositing 1.5 g of an egg
      sample containing the analytes and the analyte surrogate (norfloxacin) on sand
      (crystobalite), this material was packed into an extraction cell. Quinolones were
      extracted by flowing 6 mL of water acidified with 50 mmol/L formic acid through
      the cell heated at 100 degrees C. After pH adjustment and filtration of the
      extract, 100 microL of it was injected into the LC column. MS data acquisition
      was performed in the multiple reaction monitoring mode, selecting two precursor
      ion to product ion transitions for each target compound. Hot water appeared an
      efficient extracting medium, since absolute recoveries of the analyte in egg at
      the level of 20 ng/g were 89-103%. Estimated limits of quantification (S/N=10)
      were 0.2-0.6 ng/g. Based on the EU Commission Decision 2002/657/EC, the method
      was validated in terms of ruggedness, specificity, linearity, within-laboratory
      reproducibility, decision limit (CCalpha and detection capability (CCbeta).
      Depending on the particular analyte, CCalphas ranged between 0.41 and 2.6 ng/g,
      while CCbetas were 0.64-3.7 ng/g. The method was linear in the 3-30 ng/g range,
      with typical R(2) values higher than 0.97. The within-laboratory reproducibility
      (n=21) at 6 ng/g level was in the 9.0-12% range. After validation, a depletion
      study of enrofloxacin and one of its metabolites, i.e. ciprofloxacin, in eggs was
      conducted.

PMID- 19095238
TI  - Highly sensitive detection of human thrombin in serum by affinity capillary
      electrophoresis/laser-induced fluorescence polarization using aptamers as probes.
AB  - The detection and quantification of disease-related proteins play critical roles
      in clinical practice and diagnostic assays. We present an affinity probe
      capillary electrophoresis/laser-induced fluorescence polarization (APCE/LIFP)
      assay for detection of human thrombin using a specific aptamer as probe. In the
      APCE/LIFP assay, the mobility and fluorescence polarization of complex are
      measured simultaneously during CE analysis. The affinity complex of human
      thrombin can be well separated from unbound aptamer on CE and clearly identified
      on the basis of its fluorescence polarization and migration. Because of the
      binding favorable G-quartet conformation potentially involved in the specific
      aptamer, it was assumed that monovalent and bivalent cations promoting the
      formation of a stable G quadruplex conformation in the aptamer may enhance the
      binding of the aptamer and thrombin. Therefore, we investigated the effects of
      various metal cations on the binding of human thrombin and the aptamer. Our
      results show that cations like K(+) and Mg(2+) could not stabilize the affinity
      complex. Without the use of typical cations, a highly sensitive assay of human
      thrombin was developed with the corresponding detection limits of 4.38x10(-19)
      and 2.94x10(-19)mol in mass for standard solution and human serum, respectively.

PMID- 19095239
TI  - Retention of long-chain acetylenic hydrocarbons on non-polar stationary phases.
AB  - The retention indices of methyl and trimethylsilyl esters of octadeca-, eicosa-
      and tricosa-ynoic fatty acids containing acetylenic bonds were measured on non
      polar stationary phase (dimethylsilicone with 5% phenyl groups). An unusually
      large increase in retention is observed for compounds containing conjugated and
      methylene interrupted acetylenic bonds. The additional increase in retention
      index as a result of the presence of one conjugated acetylenic bond is roughly
      equivalent to the retention increase caused by lengthening of the hydrocarbon
      chain for one carbon atom. The increase in retention for methylene interrupted
      bonds constitutes approximately 50% increase for conjugated triple bonds. A
      further increase in interruption substantially decreases the effect. Based on
      available literature data and the results of this work, the contributions of
      conjugated acetylenic and olefinic bonds, and methylene interrupted acetylenic
      bonds to retention were estimated.

PMID- 19095240
TI  - Alkaloid profiling of the Chinese herbal medicine Fuzi by combination of matrix
      assisted laser desorption ionization mass spectrometry with liquid chromatography
      mass spectrometry.
AB  - A matrix-assisted laser desorption ionization mass spectrometry (MALDI-MS) method
      was developed for the high throughput and robust qualitative profiling of
      alkaloids in Fuzi--the processed lateral roots of the Chinese herbal medicine
      Aconitum carmichaeli Debx (A. carmichaeli). After optimization, powdered roots-
      without any further sample preparation--could be used to screen for the presence
      of Aconitum alkaloids. Furthermore, the semi-quantitative potential of MALDI-MS
      was confirmed using liquid chromatography-mass spectrometry (LC-MS) as reference.
      In total over sixty alkaloids were detected by LC-MS and fifteen of them were
      tentatively identified. Both MALDI-MS and LC-MS analysis revealed significant
      variation in alkaloid content in different (commercial) samples. LC-MS analysis
      of three toxic alkaloids in 14 batches of Fuzi resulted in a variation of their
      concentrations expressed as RSDs of 138%, 99% and 221% for aconitine,
      hypaconitine and mesaconitine, respectively. The variation in concentrations
      (expressed as RSD) of about the ninety constituents detected were classified as
      follows: 13 constituents showed an RSD of 77-100%, 46 with an RSD of 100-150%, 21
      with an RSD of 150-200% and 9 constituents with an RSD in concentration of 200
      235%. These results demonstrate a strong difference in chemical composition of
      the various Fuzi and illustrate the necessity of adequate QA/QC procedures for
      both safety and efficiency of herbal medicine. The described analytical
      procedures for alkaloid profiling could play a role in these procedures.

PMID- 19095241
TI  - Surface and volume properties of dodecylethyldimethylammonium bromide and
      benzyldimethyldodecylammonium bromide I. Surface properties of
      dodecylethyldimethylammonium bromide and benzyldimethyldodecylammonium bromide.
AB  - Surface tension measurements were carried out for aqueous solutions of two
      cationic surfactants: dodecylethyldimethylammonium bromide (C(12)(EDMAB)) and
      benzyldimethyldodecylammonium bromide (BDDAB). Isotherms and thermodynamic
      adsorption parameters were determined from the surface tension data. Firstly, the
      surface excess concentration in the adsorbed monolayer and the total
      concentration of the surfactants were determined, then the standard free energy
      of adsorption was calculated by different methods. In the calculations, different
      orientations of the surfactants at the adsorbed monolayer were also taken into
      account. From the experimental and calculated data it results that the difference
      in the structure of the two cationic surfactants by changing the methyl group for
      aryl one in their heads causes an increase of the efficiency and a decrease of
      the effectiveness of adsorption at water-air interface, and that the standard
      free energy of adsorption can be predicted from the surface tension of the
      surfactants assuming the aryl group to be equivalent to 3.5 methylene groups. The
      experimentally obtained difference between the standard free energy of adsorption
      of the C(12)(EDMAB) and BDDAB was in good agreement with that theoretically
      accounted, corresponding to the standard free energy of adsorption of the aryl
      group. However, the best correlation between the values was obtained when a
      parallel orientation of the surfactant molecules at the adsorbed monolayer was
      taken into account.

PMID- 19095242
TI  - The immobilization of 3-(chloropropyl)triethoxysilane onto silica by a simple one
      pot synthesis.
AB  - Sodium silicate from rice husk ash (RHA) was transformed to functionalized silica
      with 3-(chloropropyl)triethoxysilane (CPTES) via a simple sol-gel technique in a
      one-pot synthesis. The (29)Si MAS NMR of the organo-silica complex (RHACCl)
      showed the presence of T(2), T(3), Q(3) and Q(4) silicon centers. The (13)C MAS
      NMR showed that RHACCl had three chemical shifts at 10.37, 26.70 and 47.69 ppm
      consistent with the three carbon atoms of the CPTES moiety. The presence of
      carbon, silicon and chlorine was determined by a combination of elemental
      analysis and EDX study.

PMID- 19095243
TI  - The lyotropic phase behaviour of ester quaternary surfactants.
AB  - The lyotropic phase behaviour of two analogues of dioctadecyl dimethylammonium
      chloride was investigated. Both the inclusion of ester groups and subsequent
      minor structural rearrangement of the interfacial region of the surfactant were
      found to increase the chain melting temperature, although the overall phase
      behaviour remained similar for both compounds. Both of the two analogues were
      found to underswell, due to the formation of multi-lamellar vesicles. We also
      found that the inclusion of these ester linkages substantially reduced the
      metastability of the 'gel phase' in which the surfactants usually reside,
      accelerating the rate of collapse to a coagel state. This occurred via a
      nucleation-growth mechanism, where the growth was found to be one-dimensional,
      i.e. needle-like.

PMID- 19095244
TI  - Fabrication of ordered lamellar polyacrylamide/P123 composite membranes via
      solvent-evaporation-induced self-assembly.
AB  - A series of composite membranes of poly(ethylene oxide)-b-poly(propylene oxide)-b
      poly(ethylene oxide) (P123) and polyacrylamide (PAM) have been successfully
      prepared by solvent-evaporation-induced self-assembly. Micellar self-assembly of
      P123 in aqueous solution plays an important role as a model for the formation of
      composite membranes. XRD patterns show that the synthesized compositions are in a
      lamellar mesostructure. The lattice spacing changes with P123 concentration: the
      higher the concentration of P123, the smaller the lattice spacing of the
      composite membranes. The data on sizes and zeta potentials of pure p-PAM
      aggregates, P123 micelles, p-PAM/P123 mixtures, and c-PAM/P123 composite
      aggregates suggest that interactions take place between PAM and P123
      aggregations. The fabrication of the lamellar membranes via water-evaporation
      induced self-assembly is recorded by fluorescent emission spectroscopy and
      dynamic light-scattering methods. Based on analysis of the results, a tentative
      mechanism for the formation of the lamellar membranes has been proposed.

PMID- 19095245
TI  - Communication attitude of Italian children who do and do not stutter.
AB  - The purpose of this factorial study was to establish normative data for the
      Italian version of the Communication Attitude Test (CAT) in order to determine
      whether or not the speech-associated attitude reported by Italian children who
      stutter (CWS) differs significantly from that of their nonstuttering peers
      (CWNS). Toward this end, the Italian CAT was administered to 149 CWS and 148 CWNS
      between the ages of 6 and 14. The results showed that the mean CAT score of the
      CWS sampled is higher, to a statistically significant extent, than that of their
      nonstuttering peers. Moreover, age and gender did not differentially affect this
      result. Together, these findings and the large between-group effect size suggest
      that the CAT is a useful clinical aid in evaluating the attitude of Italian
      children whose fluency is problematic. It can serve well to determine if a
      child's speech-associated belief system needs to be addressed in therapy and, if
      so, whether or not the cognitive change tactics employed have been effective.

PMID- 19095246
TI  - ECG acquisition errors due to arm leads placed on the chest.

PMID- 19095247
TI  - Distinctive impaired cardiac autonomic modulation of heart rate variability in
      chronic Chagas' indeterminate and heart diseases.
AB  - INTRODUCTION: Cardiac autonomic dysfunction occurs in Chagas' indeterminate and
      heart disease, but comparison of this disturbance between both forms was not yet
      performed. METHODS: Time- and frequency-domain 5-minute heart rate variability in
      supine and standing positions were evaluated in 17 subjects with Chagas' disease
      with the indeterminate form, 13 with heart disease and 15 controls. Trend of
      variability indices across the groups was also tested. RESULTS: In the supine
      position, reduced time-domain and absolute frequency-domain indices reflecting
      overall autonomic modulation were observed in both Chagas' disease groups. In the
      standing position, the coefficient of variation and those frequency-domain
      indices were also reduced, and the other time-domain indices were reduced only in
      the cardiac group. Heart rate variability indices hypothesized to reflect
      relative sympathetic and parasympathetic activity showed no alteration. A
      significant graded reduction was observed in the altered indices in both
      postures, from the control to the Chagas' indeterminate and heart disease groups.
      CONCLUSION: Cardiac autonomic dysfunction, with preserved putative measures of
      sympathetic and parasympathetic modulation in relative terms, was less severe or
      absent in the indeterminate and pronounced in cardiac form of Chagas' disease.

PMID- 19095248
TI  - Access to prostate cancer care and implications for survival among minorities.

PMID- 19095249
TI  - Stromal anti-apoptotic androgen receptor target gene c-FLIP in prostate cancer.
AB  - PURPOSE: The tumor microenvironment significantly influences prostate cancer
      progression. Androgen receptor exerts its effect through downstream target genes
      to regulate prostate cancer cell proliferation. The c-FLIP gene was recently
      shown to be an androgen receptor target gene. c-FLIP is an inactive homologue of
      caspase-8 and, thus, it inhibits the death receptor mediated apoptosis pathway. c
      FLIP over expression was shown to accelerate the progression of prostate cancer
      cells to androgen independence. We evaluated the role of c-FLIP expression in
      stromal cells in prostate cancer development. MATERIALS AND METHODS: We examined
      c-FLIP expression in 53 androgen dependent and 21 androgen independent prostate
      cancer stromal cells by immunohistochemical analysis. The effects of c-FLIP over
      expression in stromal cells on the growth and invasion of LNCaP and PC3 prostate
      cancer cells were determined in indirect coculture systems. RESULTS: At the
      androgen dependent stage the stromal c-FLIP level was increased in prostate
      cancer tissue. The expression level of stromal c-FLIP was associated with tumor
      differentiation. However, stromal c-FLIP expression was not increased in androgen
      independent human prostate cancer. c-FLIP over expression in stromal cells
      stimulated the growth and invasion of prostate cancer, including LNCaP and PC3
      cells in vitro. CONCLUSIONS: These results indicate the over expression of
      stromal c-FLIP and its function for promoting prostate cancer growth and
      invasion.

PMID- 19095250
TI  - Effects of ischemia on human renal interstitial fluid metabolites.
AB  - PURPOSE: Microdialysis is a technique for monitoring the concentration of
      molecules in the interstitial fluid of living tissue. We report the effects of
      ischemia on human renal interstitial fluid molecules. MATERIALS AND METHODS: Ten
      patients with a renal mass or upper tract transitional cell carcinoma who elected
      laparoscopic nephrectomy or nephroureterectomy were studied with in situ renal
      microdialysis. Microdialysate was continuously collected into separate vials
      every 10 minutes before and after the renal artery was stapled. Samples were
      analyzed for the glucose, pyruvate, lactate and glycerol concentration. RESULTS:
      The concentration of all 4 molecules was stable throughout the pre-ischemia
      baseline period. Glucose and pyruvate concentrations decreased to almost zero
      during the first 60 minutes of ischemia. Lactate increased during the initial 60
      minutes of ischemia and then plateaued with continued ischemia. The glycerol
      concentration increased directly throughout the ischemia time. CONCLUSIONS: The
      trends of human interstitial metabolite concentrations during ischemia are
      similar to trends found in the porcine model. The human renal interstitial
      glycerol concentration increases directly throughout the duration of ischemia and
      serves as a marker of nephron damage. Microdialysis is a tool that provides real
      time, renal unit specific, minimally invasive data on the metabolic status of the
      human kidney during ischemia. It may be helpful for avoiding permanent renal
      ischemic injury.

PMID- 19095251
TI  - High intensity focused ultrasound renal tissue ablation: a laparoscopic porcine
      model.
AB  - PURPOSE: High intensity focused ultrasound for renal lesions is still
      experimental. In a porcine model we evaluated the safety and efficacy of a newly
      designed laparoscopic high intensity focused ultrasound probe and software that
      allows real-time ultrasound guidance during renal tissue ablation. MATERIALS AND
      METHODS: A Sonatherm 600 high intensity focused ultrasound system with a newly
      designed laparoscopic high intensity focused ultrasound probe was used through a
      standard Endopath 18 mm port. A total of 16 lesions were created in 15 kidneys in
      a total of 8 animals and randomized into 2 groups, including acute with sacrifice
      4 days postoperatively and subacute with sacrifice 14 days postoperatively.
      Lesion size and location varied for each surgical procedure to simulate various
      treatment scenarios. RESULTS: Mean +/- SD planned ablation volume was 7.1 +/- 5.1
      cc and mean treatment time was 7.2 +/- 06.88 minutes. For all lesions an injury
      volume was observed with a central zone of complete necrosis and no viable
      tissue. Mean total injury volume was 6.5 + 3.5 cc (range 1.1 to 13.7), comparable
      to preoperative mean planned ablation volume (p = 0.84). Mean necrosis volume was
      4.89 +/- 2.9 cc (range 0.8 to 10.5), appreciably lower than preoperative mean
      planned ablation volume (p = 0.33). Presence of the collecting system interposed
      with the treatment region did not impact the injury volume-to-planned ablation
      volume ratio or the necrosis volume-to-planned ablation volume ratio. No animals
      died before study completion. Two intraoperative complications occurred,
      including a back wall musculature burn and a ureteral burn. CONCLUSIONS:
      Laparoscopic high intensity focused ultrasound for renal tissue using the newly
      developed probe was feasible and efficacious. The ability to perform renal high
      intensity focused ultrasound through an 18 mm laparoscopic port offers a new
      alternative for renal tumor ablation.

PMID- 19095254
TI  - Comparison of manual and computer assisted ultrasonic guidance for
      transparenchymal percutaneous renal needle placement.
AB  - PURPOSE: We evaluated a novel computer based guidance system for deploying
      needles into the renal parenchyma. We compared it to current standards, including
      a fixed needle guide and a freehand technique. MATERIALS AND METHODS: We
      performed an in vitro comparison followed by a porcine trial. The in vitro model
      consisted of a bath of ultrasound medium with suspended metallic targets. We
      compared the number of attempts and the time needed by the novel guide design
      with and without its software and a support arm vs the freehand approach. In the
      porcine model we tested the software guide with and without a support arm for
      targeting a 5 mm lesion embedded in the renal parenchyma. Impressions of
      difficulty, time, the number of attempts, needle tip visualization and needle tip
      divergence were documented. RESULTS: Compared to freehand targeting the software
      guide and support arm decreased the number of targeting attempts in the in vitro
      model from 4.8 to 1.6 (p <0.001) and decreased the time required from 31.8 to
      11.4 seconds (p <0.001). In the porcine study needle tip visualization with the
      software and support arm received an average score of 1.3 vs 1.8 with the
      software guide alone (p = 0.04). Tip divergence received a score of 1.4 with the
      arm and 1.8 without it (p = 0.07). Overall contribution received a score of 1.4
      with and without the support arm (p = 0.35). CONCLUSIONS: Computer assisted
      needle deployment decreased the time and number of attempts required to
      successfully target simulated parenchymal lesions and also decreased the
      subjective difficulty inherent in the standard freehand approach.

PMID- 19095256
TI  - An experimental approach to the interrelationship between hyperthyroidism and
      ejaculation latency time in male rats.
AB  - PURPOSE: We investigated the effects of experimentally induced hyperthyroidism on
      seminal vesicle pressure measurements and bulbospongiosus muscle contractile
      activity in a para-chloroamphetamine (Sigma-Aldrich) induced ejaculation model in
      rats. MATERIALS AND METHODS: Male Wistar rats were used in the study. Daily
      injection of 25 microg/100 gm body weight L-thyroxine (T4, Sigma-Aldrich) for 14
      days was performed in 14 rats to induce hyperthyroidism. Seven L-thyroxine
      injected rats were in the hyperthyroid group. The remaining 7 rats (recovery
      group) underwent operation after a 28-day washout period to determine spontaneous
      recovery from hyperthyroidism. At each operation seminal vesicle catheterization
      was done to measure intraluminal pressure and bulbospongiosus muscle dissection
      was performed for electromyography. After intraperitoneal administration of 5
      mg/kg para-chloroamphetamine physiological parameters related to the ejaculatory
      process were measured. RESULTS: The interval between para-chloroamphetamine
      administration and first ejaculation was significantly decreased in the
      hyperthyroid rat group compared with that in the control group (mean +/- SD 202.8
      +/- 22.3 vs 465.4 +/- 104.6 seconds, p = 0.001). Seminal vesicle phasic
      contraction frequency was significantly higher than control group values in
      hyperthyroid rats (for 30 minutes 32.3 +/- 13.9, p = 0.047). The mean AUC of
      bulbospongiosus muscle electromyography activity was also significantly increased
      in this group (11.1 +/- 4.1 V per second x 10(-4), p = 0.0001). All parameters in
      recovery and control group rats were not significantly differed from each other.
      CONCLUSIONS: Hyperthyroidism leads to enhanced seminal vesicle contraction
      frequency and bulbospongiosus muscle contractile activity in rats.
      Hyperthyroidism affects the emission and expulsion phases of ejaculation in
      reversible fashion.

PMID- 19095258
TI  - Differential expression in clear cell renal cell carcinoma identified by gene
      expression profiling.
AB  - PURPOSE: Gene expression profiling has been shown to provide prognostic
      information on patients with solitary sporadic renal cell carcinoma. To our
      knowledge there is no reliable way to differentiate synchronous renal metastasis
      from bilateral primary tumors in patients with bilateral renal cell carcinoma. We
      present data using a custom kidney cancer cDNA array that can predict the outcome
      in patients with unilateral and bilateral renal cell carcinoma. MATERIALS AND
      METHODS: Fresh frozen tissue from 38 clear cell renal cell carcinomas was
      analyzed using a cancer cDNA array containing 3,966 genes relevant to cancer or
      kidney development. Median followup was 5.3 years. Cancer recurred in 12 patients
      (43%) and 11 (39%) had died by the last followup. RESULTS: Using a training data
      set of 8 tumors a 44 gene expression profile distinguishing aggressive and
      indolent clear cell renal cell carcinoma was identified. Of 29 single clear cell
      renal cell carcinomas 16 and 13 were predicted to be indolent and aggressive,
      respectively, by the gene expression profile. Recurrence-free survival at 5 years
      was 68% and 42% in these 2 groups, respectively (p = 0.032). Clear cell renal
      cell carcinoma classified as indolent or aggressive according to SSIGN (stage,
      size, grade and necrosis) score showed a 5-year recurrence-free survival rate of
      78% and 42%, respectively (p = 0.021). On Cox proportional hazards analysis the
      gene expression profile was not an independent predictor of recurrence-free
      survival after accounting for SSIGN score. Gene expression profile classification
      correlated with cancer specific survival at 5 years in 4 of 4 patients with
      metachronous clear cell renal cell carcinoma but in only 2 of 4 with bilateral
      synchronous clear cell renal cell carcinoma. CONCLUSIONS: Gene expression
      profiling using a kidney cancer relevant cDNA array can differentiate between
      aggressive and indolent clear cell renal cell carcinomas. Gene expression profile
      results may be most useful for unilateral clear cell renal cell carcinoma when
      results are discordant with predictions of tumor behavior based on standard
      clinicopathological features. In addition, gene expression profiling can provide
      prognostic information that may help characterize tumors of unknown clinical
      stage, such as bilateral metachronous clear cell renal cell carcinoma.

PMID- 19095259
TI  - Computerized tomography diagnosis of caliceal rupture.

PMID- 19095260
TI  - Sildenafil inhibits superoxide formation and prevents endothelial dysfunction in
      a mouse model of secondhand smoke induced erectile dysfunction.
AB  - PURPOSE: We determined the effect of passive secondhand cigarette smoke on 1)
      erectile function in vivo, 2) molecular mechanisms involved in penile vascular
      function, and 3) erectile function and penile molecular signaling in the presence
      of phosphodiesterase type 5 inhibitor therapy. MATERIALS AND METHODS: Four groups
      of mice were used, including group 1--controls, group 2--mice exposed to 3 weeks
      of secondhand smoke (5 hours per day for 5 days per week), group 3--control plus
      sildenafil (100 mg/kg per day) and group 4--smoke exposed plus sildenafil (100
      mg/kg per day). Cavernous nerve electrical stimulation and intracavernous
      injection of acetylcholine were done to assess erectile function. Constitutive
      and inducible nitric oxide synthase activity, reactive oxygen species generation,
      nitrotyrosine formation and superoxide anion levels were assessed. RESULTS:
      Decreased erectile responses to cavernous nerve electrical stimulation and
      impaired endothelium dependent erectile responses to ACh in mice exposed to
      secondhand smoke were observed. Superoxide anion was increased in endothelial and
      corporeal smooth muscle cells of smoking mouse penises. In mice exposed to
      secondhand smoke constitutive nitric oxide synthase activity was decreased, and
      inducible nitric oxide synthase activity, reactive oxygen species generation and
      nitrotyrosine formation increased. Sildenafil therapy restored constitutive
      nitric oxide synthase activity in the penis of smoking mice, decreased inducible
      nitric oxide synthase activity, reactive oxygen species generation and
      nitrotyrosine formation, and improved erectile responses to cavernous nerve
      electrical stimulation and acetylcholine. CONCLUSIONS: Short-term exposure to
      secondhand smoke impairs erectile function through excessive penile reactive
      oxygen species signaling and inducible nitric oxide synthase activity. Decreased
      penile constitutive nitric oxide synthase activity may be attributable to the
      decreased endothelial nitric oxide synthase activity resulting from increased
      oxidative stress. Sildenafil therapy restored nitric oxide synthase activity and
      decreased reactive oxygen species signaling, resulting in improved erectile
      function.

PMID- 19095262
TI  - New histopathological experimental model for benign prostatic hyperplasia:
      stromal hyperplasia in rats.
AB  - PURPOSE: Histological observations of clinical benign prostatic hyperplasia
      specimens show that benign prostatic hyperplasia tissue is mainly composed of
      stromal components, smooth muscle and fibrous tissue, so-called stromal
      hyperplasia. However, little is understood regarding the pathogenesis of this
      stromal hyperplasia due to no suitable stromal hyperplasia model to elucidate the
      pathology of benign prostatic hyperplasia. We created a novel model of benign
      prostatic hyperplasia accompanied by clinically relevant stromal hyperplasia.
      MATERIALS AND METHODS: The urogenital sinus isolated from male rat 20-day embryos
      was implanted into pubertal male rat ventral prostates. Two to 8 weeks after the
      operation the implanted urogenital sinus was isolated, weighed and subjected to
      histochemical analysis. To distinguish between and characterize the epithelial
      and stromal components we stained for collagen, smooth muscle components, growth
      factors and proliferating cell nuclear antigen. In addition, to determine whether
      the implanted urogenital sinus had differentiated into functional prostate we
      stained for androgen receptor and dorsolateral prostatic secretory protein.
      RESULTS: Urogenital sinuses removed from male rat 20-day embryos initially
      weighed approximately 1 mg. After implantation into host rat ventral prostates
      they grew in time dependent fashion with no apparent change in the original
      ventral prostate weight in the host rat. Implanted urogenital sinus weight was
      more than 100 mg 3 weeks after implantation. Histological observation
      demonstrated that the ratio of stromal to total area was approximately 70%, which
      was much higher than that in age matched rat ventral prostates and in a
      testosterone induced epithelial hyperplasia model (approximately 20% and 15%,
      respectively). This predominantly stromal tissue composition was maintained up to
      8 weeks after implantation. Proliferating cell nuclear antigen staining revealed
      that the ratio of proliferating cells in stroma was equal to or greater than that
      in epithelium. In this model the antiandrogen agent chlormadinone acetate (Wako
      Pure Chemicals Industries, Osaka, Japan) at a dose of 10 mg/kg prevented the
      increase in implanted urogenital sinus weight (19.1%) but its potency was less
      than that seen in the testosterone induced epithelial hyperplasia model, that is
      93.4% at the 10 mg/kg dose. CONCLUSIONS: We have established a new experimental
      stromal hyperplasia model corresponding to clinical benign prostatic hyperplasia
      in terms of the composition of stromal components and functional differentiation
      of the prostate. Furthermore, the localization and time course of growth factor
      expression were also similar to those in men with benign prostatic hyperplasia.

PMID- 19095263
TI  - CXCR3-B expression correlates with tumor necrosis extension in renal cell
      carcinoma.
AB  - PURPOSE: We investigated the expression of the 2 spliced variants of the CXCR3
      receptor (CXCR3-A and CXCR3-B) and their ligands (MIG, IP-10 and I-TAC) in
      patients with renal cell carcinoma according to conventional prognostic factors
      and the necrosis pattern. MATERIALS AND METHODS: A total of 59 patients with
      renal cell carcinoma were selected for study. Histotype, stage, grade and tumor
      diameter were first analyzed. Subsequently tumor necrosis extension, stratified
      as low-less than 30%, intermediate-30% to 75% and high-greater than 75%, was
      determined while blinded to pathological data, and CXCR3-B, IP-10, MIG and I-TAC
      mRNA levels were assessed. The overall correlation between CXCR3-B expression
      with the specific ligands, and tumor histotype, stage, grade, volume, necrosis
      extension and ligand expression were assessed on univariate and multivariate
      analyses. CXCR3-B levels stratified according to necrosis pattern were analyzed
      with the unpaired t test. RESULTS: CXCR3-B correlated with tumor necrosis and I
      TAC (p = 0.0005 and 0.032, respectively). We did not note any correlation between
      CXCR3-B and histotype, stage, grade, diameter and expression of the other ligands
      IP-10 and MIG. Moreover, I-TAC did not correlate with tumor necrosis (p =
      0.1102). In the multiple regression model a correlation between tumor necrosis
      and CXCR3-B expression was noted (p = 0.0005). Significant differences in CXCR3-B
      expression according to the necrosis pattern were observed between low and high,
      and between intermediate and high patterns (p = 0.0007 and 0.0183, respectively).
      CONCLUSIONS: Results demonstrate that CXCR3-B is an independent determinant
      factor for the extensive tumor necrosis pattern. These data emphasize the
      immunoangiostatic activity of the CXCR3/CXCR3 ligand biological axis for
      nonmetastatic human renal cell carcinoma.

PMID- 19095264
TI  - Re: Correlation of radiographic imaging and histopathology following cryoablation
      and radio frequency ablation for renal tumors: C. J. Weight, J. H. Kaouk, N. J.
      Hegarty, E. M. Remer, C. M. O'Malley, B. R. Lane, I. S. Gill and A. C. Novick, J
      Urol 2008; 179: 1277-1283.

PMID- 19095265
TI  - Vesicoureteral reflux and urinary tract infection in children with a history of
      prenatal hydronephrosis--should voiding cystourethrography be performed in cases
      of postnatally persistent grade II hydronephrosis?
AB  - PURPOSE: The clinical relevance of prenatal hydronephrosis is not well-defined.
      We determined the risk of febrile urinary tract infection in the absence of
      screening for vesicoureteral reflux, and whether postnatal voiding
      cystourethrography should be performed in patients with a history of prenatal
      hydronephrosis and postnatally persistent Society for Fetal Urology grade II
      hydronephrosis. MATERIALS AND METHODS: From a longitudinal database of patients
      with prenatal hydronephrosis maintained since 1998 we identified those with
      postnatally persistent grade II hydronephrosis. This cohort was divided into
      patients who were and were not screened with an initial voiding cystourethrogram.
      The rates of vesicoureteral reflux and development of febrile urinary tract
      infection were determined. RESULTS: Of 2,076 patients with prenatal
      hydronephrosis 1,514 had grade II hydronephrosis. Of the patients 76% underwent
      an initial voiding cystourethrogram and vesicoureteral reflux was found in 28%.
      There was no relation between laterality of hydronephrosis and incidence of
      vesicoureteral reflux. There was no difference between nonscreened and screened
      patients with respect to gender and laterality of hydronephrosis. Urinary tract
      infection developed in 1.3% of the patients who were screened and did not have
      vesicoureteral reflux and, therefore, were not receiving antibiotics. Of the
      screened patients with vesicoureteral reflux who were receiving prophylactic
      antibiotics urinary tract infection developed in 1.6% at a mean age of 9.4
      months. In 363 patients who did not undergo an initial voiding cystourethrogram
      we estimated (based on the screened population) that 101 would have
      vesicoureteral reflux and 5 would have a urinary tract infection. However, a
      febrile urinary tract infection developed in 16 patients (4.4% overall, p
      <0.0001) at a mean age of 9.3 months. Voiding cystourethrogram performed in these
      16 patients revealed vesicoureteral reflux in 12. Of all the patients with a
      urinary tract infection who were ultimately observed to have vesicoureteral
      reflux (including those initially screened and those discovered to have reflux
      after a urinary tract infection) the laterality of hydronephrosis, grade of
      reflux and laterality of reflux were comparable. CONCLUSIONS: In patients with a
      history of prenatal hydronephrosis who are observed to have postnatally
      persistent grade II hydronephrosis identification of vesicoureteral reflux and
      use of prophylactic antibiotics significantly reduce the risk of febrile urinary
      tract infection. Therefore, we recommend that patients with a history of prenatal
      hydronephrosis and postnatally persistent hydronephrosis be screened with voiding
      cystourethrography early in life, and be placed on prophylactic antibiotics until
      the screening results are known.

PMID- 19095266
TI  - Obesity does not decrease the accuracy of testicular examination in anesthetized
      boys with cryptorchidism.
AB  - PURPOSE: Given that the prevalence of childhood obesity is increasing in the
      United States, we tested the timely hypothesis that obesity hinders physical
      examination based localization of the cryptorchid testis. MATERIALS AND METHODS:
      Body mass index and percentiles of weight for height and body mass index for age
      were calculated for boys undergoing surgery for cryptorchidism at the University
      of California San Francisco Children's Hospital and Children's Hospital of
      Oakland. Two definitions of obesity were examined, ie greater than 85% or greater
      than 95% for either percentile. Patients were examined in the office and under
      general anesthesia before the skin incision. Intraoperative testicular location
      was recorded for each patient. The numbers of correct and incorrect preoperative
      determinations of testicular location were stratified by weight classification.
      Results were analyzed using contingency tables and Fisher's exact test. RESULTS:
      A total of 161 boys were recruited, accounting for 171 testes. The predictive
      value of palpating a suspected testis preoperatively with patients under
      anesthesia was greater than 95% for all weight classifications (p <0.0001). The
      predictive value of not palpating a testis preoperatively under anesthesia was
      greater than 56% for obese boys and greater than 42% for nonobese boys (p
      <0.0001). The concordance rates between examinations in the office and those
      performed under anesthesia were 90.9% and 82.7% for obese and nonobese boys,
      respectively (p = 0.51). The predictive value of not palpating a suspected
      cryptorchid testis in the office was higher in nonobese boys than in obese boys
      (81% vs 22%, p <0.0001). CONCLUSIONS: In our series childhood obesity did not
      make preoperative testicular examinations under anesthesia less accurate.
      However, office examinations may be more accurate in nonobese boys.

PMID- 19095267
TI  - Use of second look nephroscopy in children undergoing percutaneous
      nephrolithotomy.
AB  - PURPOSE: We determined the rate of stone clearance in children following
      percutaneous nephrolithotomy, endoscopic assessment of residual stone and the
      judicious use of second look nephroscopy. MATERIALS AND METHODS: We
      retrospectively reviewed the charts of all children undergoing percutaneous
      nephrolithotomy from 1996 to 2007. Cases were reviewed for pertinent details
      including preoperative and postoperative imaging, specifics of the procedure and
      followup. On completion of percutaneous nephrolithotomy the collecting system was
      assessed via combined nephrostogram and direct nephroscopy. If the collecting
      system could not be completely visualized or all stone fragments could not be
      cleared, the patient was referred for second look nephroscopy. Any residual stone
      present on initial followup imaging constituted a treatment failure. RESULTS: A
      total of 24 patients underwent percutaneous nephrolithotomy for 30 separate renal
      calculi. Mean patient age was 9.6 years, and mean stone burden was 2.53 cm. The
      success rate for percutaneous nephrolithotomy (inclusive of second look
      nephroscopy) was 87%. Of 30 cases 16 were managed by second look nephroscopy,
      with findings of residual fragments in all 16. Treatment failure was noted in 1
      patient without second look nephroscopy and in 3 patients with second look
      nephroscopy. Of the 4 patients with treatment failure all were eventually
      rendered stone-free. CONCLUSIONS: Second look nephroscopy based on endoscopic
      findings during initial percutaneous nephrolithotomy is a reliable method of
      detecting and clearing residual stone fragments. Using such a protocol we
      achieved a high success rate of stone clearance in a population of patients with
      a significant stone burden.

PMID- 19095268
TI  - Small cell carcinoma of the prostate.

PMID- 19095269
TI  - Assessment of renal injury with a clinical dual head lithotriptor delivering 240
      shock waves per minute.
AB  - PURPOSE: Lithotriptors with 2 treatment heads deliver shock waves along separate
      paths. Firing 1 head and then the other in alternating mode has been suggested as
      a strategy to treat stones twice as rapidly as with conventional shock wave
      lithotripsy. Because the shock wave rate is known to have a role in shock wave
      lithotripsy induced injury, and given that treatment using 2 separate shock wave
      sources exposes more renal tissue to shock wave energy than treatment with a
      conventional lithotriptor, we assessed renal trauma in pigs following treatment
      at rapid rate (240 shock waves per minute and 120 shock waves per minute per
      head) using a Duet lithotriptor (Direx Medical Systems, Petach Tikva, Israel)
      fired in alternating mode. MATERIALS AND METHODS: Eight adult female pigs (Hardin
      Farms, Danville, Indiana) each were treated with sham shock wave lithotripsy or
      2,400 shock waves delivered in alternating mode (1,200 shock waves per head, 120
      shock waves per minute per head and 240 shock waves per minute overall at a power
      level of 10) to the lower renal pole. Renal functional parameters, including
      glomerular filtration rate and effective renal plasma flow, were determined
      before and 1 hour after shock wave lithotripsy. The kidneys were perfusion fixed
      in situ and the hemorrhagic lesion was quantified as a percent of functional
      renal volume. RESULTS: Shock wave treatment resulted in no significant change in
      renal function and the response was similar to the functional response seen in
      sham shock wave treated animals. In 6 pigs treated with alternating mode the
      renal lesion was small at a mean +/- SEM of 0.22% +/- 0.09% of functional renal
      volume. CONCLUSIONS: Kidney tissue and function were minimally affected by a
      clinical dose of shock waves delivered in alternating mode (120 shock waves per
      minute per head and 240 shock waves per minute overall) with a Duet lithotriptor.
      These observations decrease concern that dual head lithotripsy at a rapid rate is
      inherently dangerous.

PMID- 19095270
TI  - Testing BOPA index in sewage affected soft-bottom communities in the north
      western Mediterranean.
AB  - The implementation of the European directive (ELD) 2000/60/EC has produced the
      development of several biotic indices based in benthic communities. These indices
      try to summarise ecological quality status of different communities. However, a
      universal index that works in all situations is difficult to establish, because
      there are several sources of variation. Therefore, there is the need for testing
      and validation of these indices which is required for making management decisions
      on different scales, and in different regions and communities. In this study we
      test one of these indices, BOPA index, developed by Dauvin and Ruellet [Dauvin,
      J.C., Ruellet, T., 2007. Polychaete/amphipod ratio revisited. Marine Pollution
      Bulletin 55, 215-224] in five locations affected by sewage disposal. These
      disposals are often released via outfall into shallow subtidal habitats, leading
      to a common source of pollution in coastal marine environments. BOPA index
      provides a valuable overview of the gradient status of a benthic environment,
      discriminating between stations more affected by discharge. Nevertheless, BOPA
      index, used to establish the ecological quality status, seemed to overestimate
      the status and hence there is the need to calibrate the thresholds between EcoQs
      classes as defined for these medium-to-fine sand communities, which are
      characteristics of shallow sublittoral soft-bottoms of the north-western
      Mediterranean Sea.

PMID- 19095271
TI  - [Clostridial brain abscess after glioblastoma resection: case report and critical
      review of the literature].
AB  - Clostridium perfringens is rare in neurosurgery. The source of clostridial brain
      abscess is usually a penetrating head injury. We report the case of a 57-year-old
      man who had parietal glioblastoma resection with local carmustine chemotherapy
      and who presented a clostridial brain abscess three weeks later. Progression was
      especially brutal, leading to patient's death in few hours. We discuss the
      etiology and progression of this case compared to the data reported in the
      literature.

PMID- 19095272
TI  - [Brain abscess (80 cases)].
AB  - BACKGROUND AND PURPOSE: Cerebral abscesses are focal suppurations of infectious
      origin developed within the cerebral parenchyma. This is a rare pathology, with a
      relatively poor prognosis. Therapy continues to be debated and the results are
      inconsistent. The objectives of this study were to define the factors influencing
      prognosis. METHODS: In a search for predictive factors, we analyzed 80
      observations of intracranial abscesses compiled between January 1990 and December
      2004. RESULTS: We noted a strong male prevalence (7:1) with age ranging from
      three to 65 years. The duration of symptoms was short in 34 patients (42.5%). A
      motor deficit existed in 25 cases (31.25%), aphasia in five patients, and seizure
      in 11. A CT scan in 77 patients and MRI in three patients provided the diagnosis
      in all patients. The supratentorial location was found in 72.5% of the cases.
      Otitis ranked first among etiologies, followed by cranial injuries and sinusitis.
      The pathogenic agent found in the pus from the abscess was seldom found at the
      entry point. Staphylococcus aureus was found in 12.1% of the cases, followed by
      Proteus (11.8% of the cases). Seventy-eight patients underwent surgery, two were
      treated with antibiotics only, with favorable progression in 76.3%. We noted a
      13.1% rate of complications and five deaths. CONCLUSIONS: Comparing the data from
      this study with those of the literature, we observed that progression was better
      among young patients with a mean age of 20-35 years, a good level of
      consciousness, and supratentorial location.

PMID- 19095273
TI  - Prevalence of smoking and environmental tobacco smoke exposure, and attitudes and
      beliefs towards tobacco control among Hong Kong medical students.
AB  - OBJECTIVES: To investigate the prevalence of active smoking and environmental
      tobacco smoke (ETS) exposure among medical students in Hong Kong, and their
      attitudes and beliefs towards tobacco control. STUDY DESIGN: A cross-sectional
      survey with a self-administrated questionnaire. METHODS: All medical students
      from a university in Hong Kong were invited to participate in this survey and
      completed structured questionnaires. Descriptive data analyses were performed.
      RESULT: In total, 313 medical students participated in this study (response rate
      44.7%). Only 7.2% [95% confidence interval (CI) 4.3-10.1] reported having ever
      smoked and 0.7% (95% CI 0-1.6%) were current smokers. ETS exposure at home was
      reported by 19.3% (95% CI 14.9-23.8) of students, but the proportion of ETS
      exposure in public places was much higher (61.6%, 95% CI 56.2-67.1%). More than
      85% of students had positive attitudes towards tobacco control, but 30.8% (95% CI
      25.6-36.0) disagreed with banning smoking in disco/bars/pubs. Although the
      majority (93.1%, 95% CI 90.3-96.0) of students thought that health professionals
      should receive specific training for counselling on smoking cessation, only 38.0%
      (95% CI 32.5-43.5) reported having received any formal training in this area.
      CONCLUSIONS: This study suggests that a specific professional training programme,
      including counselling on smoking cessation and actions on legislation and tobacco
      tax policy, should be built into the undergraduate medical curriculum.

PMID- 19095274
TI  - Reducing the dilution of breath samples for breath hydrogen testing.
AB  - Breath hydrogen testing has a diagnostic potential as a gastrointestinal function
      test that could be performed in general practice. The purpose of this study was
      to improve techniques for collection of breath samples and transfer of samples to
      transport vessels. Breath samples from 10 dogs were collected using both a snug
      fitting and a loose-fitting standard anesthetic mask attached to a reservoir bag,
      and a modified snug-fitting system. CO(2) was used as internal standard and mean
      CO(2) concentrations were 1.19+/-0.76, 2.17+/-0.66 and 2.68+/-0.92, respectively.
      Additional samples were saved in transport tubes for 19 days, during which the
      hydrogen and carbon dioxide concentrations remained stable. A reliable method for
      transferring the breath samples from the reservoir bag to vacuum transport tubes
      was also identified. Our results demonstrate less contamination of breath samples
      with air than previously reported, and a reproducible method to transfer breath
      samples to transport vessels.

PMID- 19095275
TI  - HIV-1 harboring renal tubular epithelial cell interaction with T cells results in
      T cell trans-infection.
AB  - Renal biopsy data suggest that renal tubular cells may serve as a reservoir for
      HIV-1, however the mechanism underlying this finding has not been studied. Here
      we show that primary human renal proximal tubular epithelial cells (HRPTECs) have
      the potential to harbor HIV-1 through the DEC-205 receptor. The interaction of
      HIV-1 with DEC-205 results in the rapid internalization of the virus for
      lysosomal degradation, without establishing a productive infection. However, a
      small fraction of incoming virus escapes degradation and can be rescued by T
      cells. Since pH-modulating agents and an inhibitor of endosomal transport
      increased HIV-1 accumulation and trans-infection to T cells, it appears that
      HRPTECs endocytic compartments may be the site of viral persistence and
      transmission to target cells. The ability of T cells to rescue the virus from
      HRPTECs further supports the hypothesis that these cells have the potential to
      serve as a reservoir for HIV-1.

PMID- 19095276
TI  - Determination of virus abundance, diversity and distribution in a municipal
      wastewater treatment plant.
AB  - Procedures to extract and count sludge viruses-like particles from municipal
      sewage treatment plant were optimized by epifluorescence microscopy using SYBR
      Green I as a stain. The highest indigenous virus yields from the bulk of the
      anaerobic digestion sludge and influent (solid) were obtained by utilizing 10 mM
      sodium pyrophosphate as eluant solution with vortex and 1 min of sonication. The
      use of 1x phosphate buffered saline as eluant with vortex and 1 min of sonication
      yields highest indigenous virus from activated sludge. The efficiency of
      extracting indigenous viruses by sodium pyrophosphate-ultrasound treatment was
      about 62% of the extractable virus particles from activated sludge and 87% for
      anaerobic digestion sludge, respectively. Samples treated with DNase had
      decreased, but not significant, virus counts, suggesting a minor effect of
      extracellular DNA on virus count. Following the optimized procedure, we
      investigated the abundance and diversity of virus particles in the wastewater
      stream of a municipal treatment plant. The concentrations of virus particles
      ranged from 0.28 x 10(9) ml(-1) to 27.04 x 10(9) ml(-1). Transmission electron
      microscopy (TEM) showed a high variety of virus morphotypes in sludge. Pulsed
      field gel electrophoresis (PFGE) revealed a diverse and dynamic viral community
      in different stages of the system with genome sizes ranging from 33 kb to >350 kb
      with most of the viral DNA in the 30-80 kb and 200-350 kb size ranges.
      Collectively, our study suggested that indigenous viruses are abundant and
      dynamic in the municipal wastewater treatment system and may play an important
      role in functioning of the system.

PMID- 19095278
TI  - The impact of flow surges on rapid gravity filtration.
AB  - In drinking water treatment flow fluctuations or surges can occur at the
      filtration stage. Pilot plant tests were carried out to investigate the impact of
      flow surges on filter performance in this study. Moreover a filtration model was
      applied to analyse the impact of flow surges on filter performance and predict
      the experimental data obtained from pilot plant tests. Experimental results
      showed that flow surges caused an increase in effluent particle concentration and
      head loss. Theoretical analysis in this study showed that the impact of a flow
      surge became more significant as the filtration run approaches the particle
      breakthrough stage. The model was also used to fit the data from one water
      treatment plant. The comparison demonstrated a good agreement.

PMID- 19095277
TI  - Sorption behavior of potential organic wastewater indicators with soils.
AB  - Soil-aquifer treatment is a wastewater treatment and reclamation option to
      facilitate beneficial water reuse. The fate of wastewater originated
      micropollutants in the soil-aquifer system is important to understand. In the
      study the sorption behavior of potential wastewater indicators such as two
      antiepileptic drugs (carbamazepine, primidone), one sulfonamide
      (sulfamethoxazole), and one corrosion inhibitor (benzotriazole) were determined
      with three natural soils (Lufa 2.2, Euro Soil 5, and Wulpen sand) that differed
      in pH, organic carbon content and particle size distribution. As aqueous phase a
      0.01M CaCl(2) solution as well as the effluent of a municipal wastewater
      treatment plant was used. Affinities of all analytes to the soil increased from
      Wulpen sand, over Lufa 2.2 to Euro Soil 5, indicating that the organic carbon
      contents might be crucial for sorption. Isotherms were well described by the
      Freundlich model. Sorption was mainly close to linear (n=0.93-1.07) for most
      target compounds and soils. Desorption gave rise to a small hysteresis only for
      Euro Soil 5 which was likely artificial, due to slow desorption kinetics beyond
      24h used in the experiment. All sorption studies confirmed that Carbamazepine,
      Benzotriazole and Primidone are appropriate to be used as wastewater indicator
      substances based on their low sorption affinity to soils, while the suitability
      of Sulfamethoxazole is limited due to the formation of non-extractable residues,
      especially at lower pH values.

PMID- 19095279
TI  - Sorption of perfluorooctane sulfonate and perfluorooctanoate on activated carbons
      and resin: Kinetic and isotherm study.
AB  - Perfluorooctane sulfonate (PFOS) and perfluorooctanoate (PFOA) have increasingly
      attracted global concerns in recent years due to their global distribution,
      persistence, strong bioaccumulation and potential toxicity. The feasibility of
      using powder activated carbon (PAC), granular activated carbon (GAC) and anion
      exchange resin (AI400) to remove PFOS and PFOA from water was investigated with
      regard to their sorption kinetics and isotherms. Sorption kinetic results show
      that the adsorbent size influenced greatly the sorption velocity, and both the
      GAC and AI400 required over 168h to achieve the equilibrium, much longer than 4h
      for the PAC. Two kinetic models were adopted to describe the experimental data,
      and the pseudo-second-order model well described the sorption of PFOS and PFOA on
      the three adsorbents. The sorption isotherms show that the GAC had the lowest
      sorption capacity both for PFOS and PFOA among the three adsorbents, while the
      PAC and AI400 possessed the highest sorption capacity of 1.04mmolg(-1) for PFOS
      and 2.92mmolg(-1) for PFOA according to the Langmuir fitting. Based on the
      sorption behaviors and the characteristics of the adsorbents and adsorbates, ion
      exchange and electrostatic interaction as well as hydrophobic interaction were
      deduced to be involved in the sorption, and some hemi-micelles and micelles
      possibly formed in the intraparticle pores.

PMID- 19095280
TI  - Probing the active site of rat porphobilinogen synthase using newly developed
      inhibitors.
AB  - The structurally related tetrapyrrolic pigments are a group of natural products
      that participate in many of the fundamental biosynthetic and catabolic processes
      of living organisms. Porphobilinogen synthase catalyzes a rate-limiting step for
      the biosyntheses of tetrapyrrolic natural products. In the present study, a
      variety of new substrate analogs and reaction intermediate analogs were
      synthesized, which were used as probes for studying the active site of rat
      porphobilinogen synthase. The compounds 1, 3, 6, 9, 14, 16, and 28 were found to
      be competitive inhibitors of rat porphobilinogen synthase with inhibition
      constants ranging from 0.96 to 73.04mM. Compounds 7, 10, 12, 13, 15, 17, 18, and
      26 were found to be irreversible enzyme inhibitors. For irreversible inhibitors,
      loose-binding inhibitors were found to give stronger inactivation. The amino
      group and carboxyl group of the analogs were found to be important for their
      binding to the enzyme. This study increased our understanding of the active site
      of porphobilinogen synthase.

PMID- 19095281
TI  - Validation of high-throughput measurement system with microwave-assisted
      extraction, fully automated sample preparation device, and gas chromatography
      electron capture detector for determination of polychlorinated biphenyls in whale
      blubber.
AB  - Validation of a high-throughput measurement system with microwave-assisted
      extraction (MAE), fully automated sample preparation device (SPD), and gas
      chromatography-electron capture detector (GC-ECD) for the determination of
      polychlorinated biphenyls (PCBs) in minke whale blubber was performed. PCB
      congeners accounting for > 95% of the total PCBs burden in blubber were
      efficiently extracted with a small volume (20 mL) of n-hexane using MAE due to
      simultaneous saponification and extraction. Further, the crude extract obtained
      by MAE was rapidly purified and automatically substituted to a small volume (1
      mL) of toluene using SPD without using concentrators. Furthermore, the
      concentration of PCBs in the purified and concentrated solution was accurately
      determined by GC-ECD. Moreover, the result of accuracy test using a certified
      material (SRM 1588b; Cod liver oil) showed good agreement with the NIST certified
      concentration values. In addition, the method quantification limit of total-PCB
      in whale blubbers was 41 ng g(-1). This new measurement system for PCBs takes
      only four hours. Consequently, it indicated this method is the most suitable for
      the monitoring and screening of PCBs in the conservation of the marine ecosystem
      and safe distribution of foods.

PMID- 19095282
TI  - A two-stage process using electrokinetic remediation and electrochemical
      degradation for treating benzo[a]pyrene spiked kaolin.
AB  - An innovative process that combines soil electrokinetic remediation and liquid
      electrochemical oxidation for the degradation of organic compounds present in a
      polluted soil was developed and evaluated by using benzo[a]pyrene spiked kaolin.
      In order to increase benzo[a]pyrene solubility during electrokinetic treatment,
      the addition of a co-solvent or surfactant, such as ethanol or Brij 35, as
      flushing solution was tested. The research carried out demonstrated the influence
      of the desorption agent employed on benzo[a]pyrene remediation from the kaolin
      matrix. Thus, if the flushing solution was ethanol at 40%, there was no presence
      of contaminant in either chamber. On the contrary, when a solution of surfactant
      Brij 35 was used, benzo[a]pyrene was transported towards the cathode chamber,
      where it was collected. Moreover, the extent of this recovery depends on the pH
      profile on the soil. When no pH control was used, around 17% of initial
      contaminant was detected in the cathode chamber; however, when pH control was
      applied, the recovery of benzo[a]pyrene could be higher than 76%, when the pH
      control in the anode chamber was set at 7.0. In order to obtain the total
      degradation of mobilised benzo[a]pyrene from the contaminated soil, the liquid
      collected by electrokinetic remediation was oxidised by electrochemical
      treatment. This oxidation was accomplished via an electrochemical cell with a
      working volume of 0.4 L, and graphite as electrode material. The benzo[a]pyrene
      was almost totally degraded in 1d, reaching a degradation of about 73% in 16 h.

PMID- 19095283
TI  - Interactions of mixed organic contaminants in uptake by rice seedlings.
AB  - Uptakes of o-chlorophenol (CP), 2,4-dichlorophenol (DCP), trichloroethylene
      (TCE), and atrazine (ATR), as single and mixed contaminants, by roots and shoots
      of rice seedlings (Oryza sativa L.) from hydroponic solutions were measured
      following a 48-h exposure of plant roots. As single contaminants, the
      concentrations of CP, DCP, and ATR in rice roots and shoots increased
      significantly with increasing concentrations in external solutions; however, TCE
      concentrations in rice roots and shoots decreased with increasing external TCE
      concentration or the exposure time. The observed bioconcentration factors (BCFs)
      of CP and DCP with roots and the BCF of ATR with shoots approximated the
      equilibrium values according to the partition-limited model. The BCF of DCP with
      shoots was about 30% of the partition limit, due to insufficient water transport
      into plants for DCP. In the ATR-CP-DCP mixed system, the BCFs of CP and DCP with
      both roots and shoots decreased significantly with increasing contaminant
      concentrations due to the enhanced mixed-contaminant phytotoxicity, as manifested
      by the greatly reduced plant transpiration rate. In the ATR-CP-DCP mixture
      system, the BCFs of ATR with roots at low concentrations were comparable with
      those for ATR alone, whereas the BCFs increased at high concentrations for an
      unknown reason. In the TCE-DCP system, TCE concentrations in roots increased with
      increasing TCE in external solutions, while TCE concentration in shoots stayed
      steady because of the strong TCE exchange at the air-leaf interface. The BCF of
      DCP with roots was comparable with that of DCP alone because there was no
      significant effect of added TCE on the plant transpiration rate.

PMID- 19095284
TI  - Congener specific distributions of polybrominated diphenyl ethers (PBDEs) in
      sediment and mussel (Mytilus edulis) of the Bo Sea, China.
AB  - Congener specific distributions of polybrominated diphenyl ethers (PBDEs) were
      investigated in sediment and mussel (Mytilus edulis) collected from the coast of
      Bo Sea, China. The median values of BDE-209 and SigmaPBDEs (including BDE-17, 
      28, -47, -66, -71, -85, -99, -100, -138, -153, -154, -183 and -190) were 2.29 and
      0.16 ng g(-1)dry weight in sediment, and 2.43 and 0.68 ng g(-1)dry weight in
      mussel, respectively. BDE-209 was the predominant congener (61-99% in mussel and
      75-99% in sediment except for one sample with 17%). Different congener patterns
      (excluding BDE-209) were observed between sediment and mussel, which were
      attributed to individual congener's bioaccumulation potential and/or the ability
      to metabolize. The four most abundant congeners were BDE-47 (40.3%), -99 (22.5%),
      -71 (8.9%) and -28 (5.8%) in sediment, and -47 (36.4%), -28 (14.5%), -154 (8.6%)
      and -71 (8.6%) in mussel, respectively. The ratios of BDE-47/BDE-99 and BDE
      100/BDE-99 in sediment were lower than those in mussel, indicating higher
      transformation and uptake rate of BDE-99 in mussel. The biota-sediment
      accumulation factor (BSAF) of individual PBDE congeners declined with the
      increase of their logarithm of octanol-water partition coefficients (log K(OW))
      except for BDE-154, indicating congeners with higher logK(OW) were more likely to
      retain in sediment. These can be explained with a high affinity of these
      compounds for carbonaceous geosorbents, and molecular steric hindrance that
      limits large, very hydrophobic organic compounds from penetrating the cellular
      membranes.

PMID- 19095285
TI  - Ecotoxicity of the degradation products of triphenylborane pyridine (TPBP)
      antifouling agent.
AB  - Triphenylborane pyridine (TPBP) is an alternative to organotin antifouling
      compounds. This work aimed to identify the unknown Peak #1, and to evaluate the
      ecotoxicity of TPBP and its degradation products. Peak #1 was produced from TPBP
      dissolved in acetonitrile under UV-A photolysis using a high-pressure mercury
      lamp. The Peak #1 fraction was purified using two-step column chromatography from
      a TPBP-acetonitrile solution. The major compound of the fraction was identified
      as being biphenyl from the 1H NMR and 13C NMR spectra. The ecotoxicity of four
      degradation products (diphenylborane hydroxide, phenylborane dihydroxide, phenol,
      and biphenyl) and TPBP towards two marine planktons were assessed. The 48 h
      LC(50) values of the crustacean, Artemia salina, were 0.13 mg L(-1) for TPBP, 14
      mg L(-1) for biphenyl, 17 mg L(-1) for phenol, and > 50 mg L(-1) for the other
      degradation products. The 72 h EC(50) values of the diatom, Skeletonema costatum,
      were 0.0022 mg L(-1) for TPBP, 1.2 mg L(-1) for biphenyl, and > 2 mg L(-1) for
      the other degradation products. Thus, the ecotoxicity of biphenyl and the other
      degradation products were not high compared to the parent compound, TPBP.

PMID- 19095286
TI  - Enantioselective induction of estrogen-responsive gene expression by permethrin
      enantiomers in embryo-larval zebrafish.
AB  - Enantioselectivity in the separation, toxicology, biodegradation and estrogenic
      activity of chiral pesticides has become a groundbreaking topic recently. In this
      study, real-time, quantitative polymerase chain reaction was adapted to
      investigate the induction of estrogen-responsive gene expression in embryo-larval
      zebrafish after 7 d of exposure to permethrin (PM) enantiomers. The PM
      enantiomers were completely separated by a chiral HPLC column. The in vivo study
      found that a 7 d exposure to 250 ng L(-1) PM racemate and its enantiomers was
      sufficient to stimulate vtg1, esralpha and cyp19b expression, while 1000 ng L(-1)
      exposure significantly induced gene expression in a pattern similar to that of
      the control (50 ng L(-1) E2), except for vtg2. Significant differences were
      detected between the enantiomers in the induction of estrogen-responsive gene
      expression. At the exposure level of 1000 ng L(-1), the vtg1, esralpha and cyp19b
      responses to the (-)-trans enantiomer were about 3.2-, 1.8- and 1.5-fold higher,
      respectively, than those in the group treated with (+)-trans enantiomer (p <
      0.05). In the two cis-enantiomer treatment groups, (+)-cis increased the mRNA
      level of the cyp19b gene about 1.5-fold higher than the (-)-cis-enantiomer did.
      Of the four enantiomers, the (-)-trans enantiomer showed the greatest estrogenic
      activity. The results strongly indicate the occurrence of significant
      enantioselectivity in estrogenic activity of PM enantiomers exposed to embryo
      larval zebrafish. These findings add to a growing body of evidence concerning
      enantioselectivity in the toxicity, endocrine-disrupting activity, and
      environmental biodegradation of chiral pesticides.

PMID- 19095287
TI  - A method to measure total antioxidant capacity against peroxyl radicals in
      aquatic organisms: application to evaluate microcystins toxicity.
AB  - Determination of total antioxidant capacity, instead of the measurements of
      limited number of antioxidants, is very important for the understanding of how
      antioxidants interact with reactive oxygen species (ROS). Several techniques
      already exist with this propose, although some of them are extremely time
      consuming. A new methodology is proposed, based on the detection of ROS by
      fluorometry (ex/em: 485/520 nm) employing 2',7'-dichlorofluorescein diacetate
      (H(2)DCF-DA) as substrate. Supernatant of homogenized samples from different
      organs (gill, muscle, liver, and brain) of the teleost fish Jenynsia multidentata
      (Anaplebidae) were exposed to peroxyl radicals generated by thermal (35 degrees
      C) decomposition of 2,2'-azobis (2 methylpropionamidine) dihydrochloride (ABAP, 4
      mM). Different protein concentrations (0.5, 1, 2 and 8 mg/ml) were assayed to get
      the best signal and curve fitting of fluorescence data over time (30 min). Total
      antioxidant capacity against peroxyl radicals was estimated as the difference in
      ROS area with and without ABAP, relative to the fluorescence registered without
      ABAP. For application of this methodology, J. multidentata specimens were exposed
      for 24 h to microcystins, cyanotoxins known to induce oxidative stress. Almost
      all organs showed a lower antioxidant capacity (p<0.05) in samples with 8 mg
      proteins/ml, when compared to protein content of 1-2 mg/ml. In liver samples,
      higher (p<0.05) free iron content was determined in samples with 8 mg
      proteins/ml. Sensitivity test employing GSH spiked in homogenized samples showed
      the protocol efficiency in detecting total antioxidant capacity. In the test with
      microcystins a dose-dependent decrease (p<0.05) of antioxidant competence in
      gills and brain and an inverse result with liver samples were observed. The use
      of antioxidant defenses was efficient in avoiding oxidative damage, as the
      content of oxidized proteins was not altered. Data obtained show the potential of
      this new methodology to be used in ecotoxicological studies.

PMID- 19095288
TI  - Changes in point and diffuse source phosphorus inputs to the River Frome (Dorset,
      UK) from 1966 to 2006.
AB  - Changes in the relationship between soluble reactive phosphorus (SRP)
      concentration and river flow between 1966 and 2006 were assessed for the River
      Frome, UK using the recently developed Load Apportionment Model. The resulting
      source load estimates gave good agreement with known changes within the
      catchment. The model indicated an increase in point source contribution to the
      total river load from 46% to 62% between 1970 and 1985. This corresponded with
      the population increase within the catchment during that time. The predicted mean
      SRP load was highest between 1996 and 2000 (30 t y(-1)), with 49% coming from
      point sources. Despite no lowering in population or major changes in agricultural
      practice, the model predicted a reduced load of 18.1 t y(-1) for the period 2001
      to 2005, due mainly to a decrease in point source inputs from 14.6 t y(-1) to 6.1
      t y(-1) (equivalent to 34% of the total load). This prediction matches the major
      improvements in sewage treatment that occurred within the catchment in 2002. This
      study thus provides a major validation of the Load Apportionment Model. The model
      provides an effective and rapid method of determining past changes in phosphorus
      sources, based entirely on the P concentration - flow relationship: critically,
      it does not require any historical information on land use, fertiliser
      application rates, topography, soil types and sewage inputs. Further decreases in
      SRP concentration in the River Frome during the algal growing season would be
      best achieved by further reductions of STW inputs.

PMID- 19095289
TI  - Urinary 1-hydroxypyrene and PAH exposure in 4-year-old Spanish children.
AB  - AIMS: Exposure to polycyclic aromatic hydrocarbons (PAH), among the main
      compounds present in polluted urban air, is of concern for children's health.
      Childhood exposure to PAH was assessed by urinary monitoring of 1-hydroxypyrene
      (1-OHP), a pyrene metabolite, investigating its association with exposure to air
      pollution and other factors related to PAH in air. METHODS: A group of 174 4-year
      old children were recruited and a questionnaire on their indoor and outdoor
      residential environment was completed by parents. At the same time, environmental
      measurements of traffic-related air pollution (NO2) were carried out. A urine
      sample was collected from each child in order to analyze 1-OHP using HPLC with
      fluorescence detection, correcting for creatinine concentrations. Non-parametric
      tests and regression analyses were used to identify environmental factors that
      influence 1-OHP excretion. RESULTS: Mean urinary 1-OHP concentration was 0.061
      micromol/mol creatinine, ranging from 0.004 to 0.314 micromol/mol. Non-parametric
      tests and regression analysis showed positive and significant associations
      (P<or=0.05) between 1-OHP and predicted residential exposure to NO2 (which was
      based on outdoor environmental measurements and geo-statistical analysis), self
      reported residential vehicle traffic, passive smoking and cooking appliance. 1
      OHP levels tended to be higher among children living in urban areas (0.062
      micromol/mol vs. 0.058 micromol/mol for children living in rural areas) but
      differences were not significant (P=0.20). CONCLUSION: In Southern Spain,
      concentrations of urinary 1-OHP were in the lower range of those generally
      reported for children living in non-polluted areas in Western Europe and the USA.
      Traffic-related air pollution, passive smoking and cooking appliance influenced
      urinary 1-OHP level in the children, which should be prevented due to the health
      consequences of the inadvertent exposure to PAH during development.

PMID- 19095290
TI  - Life cycle assessment of ecological sanitation system for small-scale wastewater
      treatment.
AB  - Ecological sanitation (EcoSan) concepts, relying on an environmentally sound
      management of water, nutrient and energy fluxes, have been poorly characterized
      in literature and are widely ignored by public planning authorities, architects
      or engineers. A comparative life cycle assessment (LCA) of an EcoSan system at an
      office building and of conventional systems was carried out in order to provide
      practical data and information to (partially) fill this gap. Compared to
      conventional systems, EcoSan can reduce the contribution to ecosystem quality
      damage by more than 60%. EcoSan leads, however, to higher damages on resources
      and human health and higher impact on climate change. Key improvement
      possibilities and research needs related to these results are discussed
      throughout the paper. Ecological sanitation appears to be a promising alternative
      to small-scale wastewater treatment. At higher scales, low water consumption
      conventional systems are better performing and are not likely to be replaced by
      EcoSan systems in the short term. Standard conventional systems have very poor
      environmental performances and should be upgraded as far as possible.

PMID- 19095291
TI  - Assessment of the chemical contamination in home-produced eggs in Belgium:
      general overview of the CONTEGG study.
AB  - This overview paper describes a study conducted for the Belgian Federal Public
      Service of Health, Food Chain Safety and Environment during 2006-2007. Home
      produced eggs from Belgian private owners of hens were included in a large study
      aiming to determine concentration levels of various environmental contaminants.
      By means of the analyses of soil samples and of kitchen waste samples, obtained
      from the same locations, an investigation towards the possible sources of
      contaminants was possible. Eggs, soils, faeces and kitchen waste samples were
      checked for the presence of dioxins, PCBs (including dioxin-like PCBs),
      organochlorine pesticides, trace elements, PAHs, brominated flame retardants and
      mycotoxins. The study design, sampling methodology and primary conclusions of the
      study are given. It was found that in some cases dioxin-like compounds were
      present at levels that are of concern for the health of the egg consumers.
      Therefore, measures to limit their contamination in eggs, produced by hens of
      private owners, were proposed and deserve further attention.

PMID- 19095292
TI  - Lead contamination of inexpensive seasonal and holiday products.
AB  - Lead is a potent neurotoxin and because of this, the US regulatory limit for lead
      content of paint on items intended for children is 0.06% by weight. There were
      numerous recalls of name-brand toys in the United States for lead paint
      contamination during 2007. Most of these items were manufactured in China.
      Seasonal and holiday items are inexpensive and often directed specifically toward
      children, yet the use of lead paints in these products has not been widely
      recognized. The objective of this study was to determine the extent of lead
      contamination in this product category. Ninety-five samples were tested,
      including primarily Halloween and Easter products. Twelve of the products were
      found to contain lead in excess of the current US regulatory limit of 0.06% by
      weight for lead in paints on items intended for children. The high percentage of
      products found to be contaminated in this limited sampling implies that many more
      lead-painted items are being sold. These results suggest that the potential
      hazards of seasonal and holiday products deserve the attention of government
      agencies seeking to limit the exposure of children to lead.

PMID- 19095293
TI  - Willingness-to-pay stated preferences for 8 health-related quality-of-life
      domains in psoriatic arthritis: a pilot study.
AB  - OBJECTIVES: Psoriatic arthritis (PsA) is a seronegative inflammatory arthritis
      found in up to 5 to 42% of patients with psoriasis. As current instruments do not
      fully capture health-related quality of life (HR-QOL) in PsA from the patient's
      perspective, we piloted a novel application of "willingness-to-pay" (WTP) as a
      Patient Reported Outcome to measure the relative impact of PsA in 8 domains of HR
      QOL. METHODS: Fifty-nine PsA patients were interviewed on 8 WTP HR-QOL domains
      (physical, emotional, sleep, work, social, self-care, intimacy, and
      concentration). Participants were asked to rank the 8 domains of health in order
      of HR-QOL impact. In each domain, participants were asked whether PsA affected
      that domain, whether they were willing to pay for a cure in that domain, and the
      amount they were willing to pay. Median WTP amounts were compared with the
      proportion of participants affected by and willing to pay in each domain.
      Responses in US dollars were interpreted as strength of preference rather than
      absolute monetary values. RESULTS: The majority of participants were white (98%),
      > or =45 years of age (70%), insured (98%), and earned >$65,000/yr (66%). The
      physical domain was most affected by PsA; intimacy and concentration were ranked
      lowest. Participants reported a wide range of WTP amounts ($0 to $1,000,000), and
      median WTP amounts were highest in the physical, work, sleep, and self-care
      domains. Related domains elicited median WTP amounts that were highly correlated.
      No significant differences in median WTP amounts were found across ages, genders,
      and income levels for the different domains. CONCLUSIONS: WTP is a novel
      quantitative patient-perspective measure that is comprehensible and feasible to
      administer in PsA patients. It represents a unique tool for capturing the complex
      manifestations of PsA and its impact on the individual, allowing the
      quantification of specific HR-QOL parameters and providing the potential for
      comparison across various disease processes in a given individual.

PMID- 19095294
TI  - Wnt pathway and IL-17: novel regulators of joint remodeling in rheumatic
      diseases. Looking beyond the RANK-RANKL-OPG axis.
AB  - OBJECTIVES: During the last decade research has focused on the RANK-RANKL-OPG
      (Receptor Activator of Nuclear factor KappaB-Receptor Activator of Nuclear factor
      KappaB Ligand-Osteoprotegerin) pathway that is currently considered the final
      common route to bone and joint remodeling. The potential role of novel additional
      mediators has been highlighted by several reports. This review focuses on the
      recent information about the pathophysiology of the Wingless (Wnt) pathway and
      interleukin-17 (IL-17) in relation of their role in bone and joint remodeling.
      METHODS: An extensive internet search was performed (PubMed) from 1998 and onward
      using the following keywords: Wnt, bone remodeling, bone, rheumatic diseases,
      rheumatoid arthritis, IL-17, Th17, osteoblastogenesis, and osteoclastogenesis.
      RESULTS: Several members of the Wnt pathway play an important role in bone
      remodeling. Recent experimental data indicate a key role for Dickkopf-1, a
      soluble inhibitor of the Wnt pathway, in bone remodeling. Increased Dickkopf-1
      levels are linked to bone resorption and decreased levels to new bone formation.
      Low-density lipoprotein receptor-related protein-5, the main receptor that
      mediates Wnt signaling, plays a critical role in bone mass regulation. Gain-of
      function mutations of lipoprotein receptor-related protein-5 cause high bone mass
      phenotypes, whereas loss-of-function mutations are linked to severe osteoporosis.
      IL-17 is a proinflammatory cytokine that is produced by a recently described T
      cell subset, known as Th17 cells. Evidence suggests that IL-17 is a critical
      mediator of joint destruction in animal models of arthritis. IL-17 blockade has
      beneficial effects on murine arthritis, a fact that points to the direction of
      this cytokine as a potential therapeutic target in human inflammatory arthritides
      as well. CONCLUSIONS: The available data suggest that mediators in these 2
      biologic systems are critical in joint remodeling and may be appropriate targets
      in the treatment of bone and joint abnormalities that characterize a variety of
      inflammatory arthritides and bone diseases.

PMID- 19095295
TI  - Functional properties of feline foot pads as studied by lectin histochemical and
      immunohistochemical methods.
AB  - The localization of sialic acids and antimicrobial substances in the foot pads of
      the cat was examined by lectin histochemical and immunohistochemical methods. The
      lectin binding patterns of the eccrine glands were suggestive of the existence of
      large concentrations of sialoglycoconjugates that terminated in Siaalpha2-3Gal1
      4GlcNAc. Results were consistent with localization of O-linked (mucin-type)
      sialoglycoproteins with the Siaalpha2-6Gal/GalNAc sequence in the epidermal
      layers, especially the stratum spinosum. Additionally, antimicrobial peptides,
      such as lysozyme, secretory component, lactoferrin, and the peptide group of beta
      defensins were demonstrated to be immunolocalised in the eccrine glandular cells.
      These substances, except for secretory component, were also distributed in the
      epidermal strata. The sialic acids and antimicrobial substances found in the
      eccrine glandular secretions and epidermis may play an essential role in the
      preservation of skin integrity in feline foot pads.

PMID- 19095296
TI  - SFRP1 and SFRP2 suppress the transformation and invasion abilities of cervical
      cancer cells through Wnt signal pathway.
AB  - OBJECTIVES: Aberrant activation of the Wnt/beta-catenin signaling pathway is
      common in human cancers, including cervical cancer. The secreted frizzled-related
      proteins (SFRPs) function as Wnt antagonists and play important implications in
      carcinogenesis. Recently, we have shown that SFRP1 and SFRP2 are frequently
      downregulated through promoter hypermethylation. However, the function of SFRP1
      and SFRP2 in cervical cancer remains unclear. METHODS: To improve our
      understanding of the role of SFRP1 and SFRP2 in cervical cancer cells, we use
      overexpression or shRNA approach in cervical cancer cell lines. RESULTS:
      Restoration of the expression of SFRP1 and SFRP2 attenuated Wnt signaling in
      CaSki cells, decreased abnormal accumulation of free beta-catenin in the nucleus,
      and suppressed cancer cell growth. In addition, different statuses of beta
      catenin accumulation in the cytoplasm of CaSki or HeLa3rd cells were observed,
      suggesting that different Wnt pathways are executed. Furthermore, we demonstrated
      that SFRP1 and SFRP2 enhance the expression of the epithelial marker E-cadherin,
      through inhibition of the expression of SLUG, TWIST and SNAIL, three
      transcription factors involved in the epithelial mesenchymal transition (EMT)
      program. Finally, in a xenograft animal model, we showed that SFRP1 suppresses
      tumorigenicity of cancer cells in vivo. CONCLUSIONS: Taken together, these data
      strongly suggest that epigenetic silencing of SFRP genes leads to oncogenic
      activation of the Wnt pathway and contributes to cervical cancer progression
      through the EMT program.

PMID- 19095297
TI  - The roles of PGF(2alpha) and PGE(2) in regression of the corpus luteum after
      intrauterine infusion of Arcanobacterium pyogenes in cows.
AB  - To study the effect of bacteria in the uterus on the fate of the corpus luteum
      (CL), Arcanobacterium pyogenes was inoculated into the uteri of cows on Day 3
      (Day 0=day of spontaneous ovulation). Plasma concentrations of 13,14-dihydro-15
      keto-PGF(2alpha) (PGFM), 13,14-dihydro-15-keto-PGE(2) (PGEM) and progesterone
      (P(4)) were determined. In five cows, the developing CL regressed and first-wave
      dominant follicles, which normally become atretic, ovulated (Group OV) after
      bacterial inoculation. In another five cows (Group NOV) and five control cows,
      the developing CL did not regress and first-wave dominant follicles did not
      ovulate. In Group OV, PGFM concentrations increased by 126.2pg/mL (from 36.8+/
      7.8pg/mL on Day 3 to 163+/-37.2pg/mL on Day 6), with an increase ratio of 5.8
      fold. Conversely, in Group NOV, PGFM had a greater increase of 198.4pg/mL (from
      128.2+/-27.8pg/mL on Day 3 to 326.6+/-115.1pg/mL on Day 5), but the increase
      ratio was only 2.3-fold. Although PGEM tended to increase in both groups, raw
      increases and increase ratios were small. Bacterial inoculation into the uterus
      stimulated the release of prostaglandins and affected the fate of the CL; in that
      regard, the CL was affected more by PGF(2alpha) than by PGE(2), and the increase
      ratio of PGF(2alpha) was more important than the raw increase.

PMID- 19095298
TI  - Enhanced osteoblast function on ultraviolet light-treated zirconia.
AB  - Unlike titanium, surface roughening of zirconia for enhanced bone integration has
      been technically challenging. The photochemical reaction of semiconductor oxides,
      e.g., titanium dioxide, has earned considerable and broad interest in
      environmental and clean energy sciences. This study determined whether
      ultraviolet (UV) light treatment of zirconia enhances its bioactivity on
      osteoblasts. Machined zirconia disks were treated with UV light for various time
      periods up to 48 h. UV light treatment for 48 h increased the rates of
      attachment, spread, and proliferation of rat bone marrow-derived osteoblasts.
      Alkaline phosphatase-positive and mineralized nodule areas doubled on UV light
      treated zirconia. The expression of osteoblastic genes, such as osteopontin and
      osteocalcin, was not modulated by UV light treatment. X-ray diffraction and X-ray
      photoelectron spectroscopy analyses showed that zirconia disks consisted of
      monoclinic and tetragonal phases of ZrO(2) and Y(2)O(3) having a wide light
      absorption band of 200-400 nm with its peak at <250 nm. UV light treatment
      transformed the zirconia surface from hydrophobic to hydrophilic status and
      reduced the atomic percentage of surface carbon in a UV light dose-dependent
      manner. These results suggest that UV treatment of yttrium-containing partially
      stabilized zirconia enhances its bioactivity on osteoblasts, in terms of their
      attachment, proliferation, and eventually mineralization. This
      biofunctionalization was associated with UV light-catalytic hydrophilic
      conversion of zirconia surfaces and progressive removal of hydrocarbons.

PMID- 19095299
TI  - The adsorption of preferential binding peptides to apatite-based materials.
AB  - The objective of this work was to identify peptide sequences with high affinity
      to bone-like mineral (BLM) to provide alternative design methods for functional
      bone regeneration peptides. Adsorption of preferential binding peptide sequences
      on four apatite-based substrates [BLM and three sintered apatite disks pressed
      from powders containing 0% CO(3)(2-) (HA), 5.6% CO(3)(2-) (CA5), 10.5% CO(3)(2-)
      (CA10)] with varied compositions and morphologies was investigated. A combination
      of phage display, ELISA, and computational modeling was used to elucidate three
      12-mer peptide sequences APWHLSSQYSRT (A), STLPIPHEFSRE (S), and VTKHLNQISQSY
      (V), from 243 candidates with preferential adsorption on BLM and HA. Overall,
      peptides S and V have a significantly higher adsorption to the apatite-based
      materials in comparison to peptide A (for S vs. A, BLM p=0.001, CA5 p<0.001, CA10
      p<0.001, HA p=0.038; for V vs. A, BLM p=0.006, CA5 p=0.033, CA10 p=0.029). FT-IR
      analysis displayed carbonate levels in CA5 and CA10 dropped to approximately 1.1
      2.2% after sintering, whereas SEM imaging displayed CA5 and CA10 possess distinct
      morphologies. Adsorption results normalized to surface area indicate that small
      changes in carbonate percentage at a similar morphological scale did not provide
      enough carbonate incorporation to show statistical differences in peptide
      adsorption. Because the identified peptides (S and V) have preferential binding
      to apatite, their use can now be investigated in bone and dentin tissue
      engineering, tendon and ligament repair, and enamel formation.

PMID- 19095300
TI  - Ovine amniotic fluid volume response to intra-amniotic balloon filling.

PMID- 19095301
TI  - IFPA Trophoblast Research Award Lecture: the dynamic role of Bcl-2 family members
      in trophoblast cell fate.
AB  - Bcl-2 family members are important regulators of cell fate in normal organ
      development and in disease status. Pro- and anti-apoptotic members of this family
      function through a complex network of homo- and hetero-dimers to determine
      whether a cell lives or dies. Members of the Bcl-2 family are classically
      recognized for their role in apoptosis, yet emerging evidence has highlighted
      their importance in the regulation of cell cycle. Cellular proliferation,
      differentiation and death accompany early placental development of the
      trophoblast lineage. We have recently reported on the expression and function of
      two Bcl-2 family members in normal placental development, namely the pro
      apoptotic Mtd/Bok, and its anti-apoptotic partner Mcl-1 and have found that their
      expression is upregulated by low oxygen, a key mediator of trophoblast cell
      proliferation in early placentation. Interestingly, we have also reported that
      the expression of the Mtd/Mcl-1 system is altered in preeclampsia, a placental
      pathology associated with a status of oxidative stress and typically
      characterized by an immature proliferative trophoblast phenotype and excessive
      trophoblast cell death. In this pathology levels of pro-apototic Mtd-L and Mtd-P
      are increased and anti-apoptotic Mcl-1 is cleaved in to a pro-apoptotic isoform.
      Disruption in Mtd/Mcl-1 expression seen in preeclampsia may contribute to both
      the increased apoptosis and hyperproliferative nature of this disorder.

PMID- 19095303
TI  - How to use clinical vignettes in hematology--a pilot survey in the context of
      chronic lymphocytic leukemia.
AB  - RATIONALE: Case vignettes have been validated as an efficient tool for assessing
      the quality of clinical practices, and have been used in a variety of medical
      settings. However, their use in the field of hematology has not been tested.
      OBJECTIVES: We undertook a study to pre-test seven case vignettes, and thereby to
      assess practice patterns and, when possible, guideline adherence in the treatment
      of chronic lymphocytic leukemia (CLL) by French hematologists. FINDINGS: Of the
      64 hematologists who agreed to participate, 26 (41%) completed the vignettes. We
      found significant differences in the physicians' patterns of ordering further
      investigations among young and old patients in the same clinical context. This is
      not consistent with published guidelines. Moreover, the most striking differences
      concerned the physicians' interpretations of prognostic factors and the use of
      radiological testing before treatment. Modalities of treatment were variable
      across clinical situations, especially with regard to second-line treatments.
      Clinicians understood the vignettes well, except for those that dealt with stem
      cell transplantation. CONCLUSIONS: This pilot study showed the feasibility of the
      use of case vignettes to assess the quality of clinical practice in CLL. The
      initial results identified deviations from the published guidelines. A large
      scale European survey will commence in a few months.

PMID- 19095304
TI  - Female impulsive aggression: a sleep research perspective.
AB  - The rate of violent crimes among girls and women appears to be increasing. One in
      every five female prisoners has been reported to have antisocial personality
      disorder. However, it has been quite unclear whether the impulsive, aggressive
      behaviour among women is affected by the same biological mechanisms as among men.
      Psychiatric sleep research has attempted to identify diagnostically sensitive and
      specific sleep patterns associated with particular disorders. Most psychiatric
      disorders are typically characterized by a severe sleep disturbance associated
      with decreased amounts of slow wave sleep (SWS), the physiologically significant,
      refreshing part of sleep. Among men with antisocial behaviour with severe
      aggression, on the contrary, increased SWS has been reported, reflecting either
      specific brain pathology or a delay in the normal development of human sleep
      patterns. In our preliminary study among medication-free, detoxified female
      homicidal offenders with antisocial personality disorder, the same profound
      abnormality in sleep architecture was found. From the perspective of sleep
      research, the biological correlates of severe impulsive aggression seem to share
      similar features in both sexes.

PMID- 19095305
TI  - Persistent organic pollutant residues in the sediments and mollusks from the
      Bohai Sea coastal areas, North China: an overview.
AB  - The Bohai Sea costal area is one of the most developed zones of China and the
      sewage water from populous and developed cities, including Beijing, Tianjin,
      Qinhuangdao and Dalian is discharged into the Bohai Sea. Additionally, its semi
      enclosed characteristic restricts water exchange, which leads to high
      accumulation of pollutants in the environment. This overview presents the
      residues of 6 classes of Persistent Organic Pollutants (POPs), including PAHs,
      DDTs, HCHs, PCBs and PCDD/Fs, in the sediments and mollusks of the Bohai Sea
      through analyzing previous literatures. In the sediments, the highest PAH
      concentrations were detected in the vicinities of Qinhuangdao, while the
      northeast corner of the Bohai Bay possessed the highest levels of DDTs and PCBs.
      The investigations on HCHs and PCDD/Fs distributions on the whole sea scale have
      not been reported. In mollusks, PAH concentrations were in the same order of
      magnitude in the whole Bohai Sea, so were DDTs, HCHs and PCBs, while the outlier
      maximum values of PCDDs and PCDFs occurred in Yingkou. In general, the POPs
      residues in mollusks collected from Shandong Province were higher than the other
      areas. The compositions of DDTs, HCHs and PCBs in sediments indicated their
      recent usage. By comparing POP concentrations in sediments with the recommended
      criterions, it was shown that some individual PAH compounds occasionally
      associated with adverse biological effects in the vicinities of the Liaodong Bay
      and Qinhuangdao, and the Liaohe River Estuary were heavily contaminated with
      DDTs, but PCBs were all below the thresholds. In order to reveal the transference
      and transformation of POPs in the environment, further studies concerning with
      their behavior, fate and bioaccumulation in the different trophic levels should
      be programmed. Moreover, laws and regulations should be enforced to ban the
      illegal usage of POPs-containing pesticides to guarantee health of the
      environment and human.

PMID- 19095306
TI  - Glutathione depletion reveals impairment of antigen processing and inhibition of
      cathepsin activity by nitric oxide in antigen-presenting cells.
AB  - Nitric oxide has been shown to induce immunosuppression by inhibiting class II
      MHC molecule expression and T-lymphocyte proliferation. However, much less is
      known about the ability of NO to interfere with antigen processing and
      presentation. So we questioned whether B lymphoma cells exposed to NO could be
      impaired in their ability to process lysozyme and to stimulate proliferation of a
      syngeneic T-cell hybridoma. As immunosuppressive pathological conditions are
      often associated with a pro-oxidative milieu, we also examined the influence of
      intracellular GSH levels on NO responsiveness. Exposure of GSH-depleted B cells
      to NO-releasing compounds lowered their capacity to present a reduced and
      alkylated lysozyme (TAP-HEL), although presentation of a lysozyme-derived peptide
      was unaffected. Cells with a normal GSH content were protected from this
      inhibition. Fluid phase endocytosis, protein synthesis and expression of class II
      molecules remained normal in GSH-depleted cells. However, proteolysis of a dye
      conjugate of ovalbumin was strongly inhibited, suggesting that protease
      inhibition might be involved. Cathepsin B activity, which was necessary to TAP
      HEL processing, was inhibited by the NO-donors. The inhibition was higher in GSH
      depleted cells and reproduced by treatment of A20 B cells by two cathepsin
      inhibitors. These results show that, in addition to cytostasis and reduction in
      class II expression, NO-induced immunosuppression could also implicate inhibition
      of antigen processing under oxidative stress conditions.

PMID- 19095307
TI  - Reconstitution inflammatory syndrome related to histoplasmosis, with a
      hemophagocytic syndrome in HIV infection.
AB  - Immune reconstitution after initiation of antiretroviral therapy may unmask a
      latent infection. We report a case of disseminated Histoplasma capsulatum
      capsulatum infection associated with a hemophagocytic syndrome in an HIV-infected
      patient, three weeks after initiation of antiretroviral therapy. The immune
      reconstitution inflammatory syndrome might be a risk factor for hemophagocytosis.

PMID- 19095308
TI  - Prediction of childhood cognitive abilities from a set of early indicators of
      information processing capabilities.
AB  - Childhood tests of intelligence are often composed of several different tasks or
      scales. In contrast to this, many studies assessing early indicators of cognitive
      ability include only one or two different infant paradigms. The present study
      employs an extended set of infant paradigms for the prediction of childhood
      development and intelligence. Two groups of infants (64 three- and 63 six-months
      olds) were tested. Subjects were retested at 24- and 32-months of age with
      several indicators related to developmental state, verbal skills and
      intelligence. Especially in the group of 6-month-olds, the analysis demonstrated
      that significant R(2) contributions were yielded by a set of different predictor
      variables. The results show that a set of predictors in contrast to single
      predictors leads to a substantial increase of the variance accounted for.

PMID- 19095309
TI  - p38 mitogen-activated kinase (MAPK) is essential for equine neutrophil migration.
AB  - Equine laminar tissues do not contain resident neutrophils and have less
      superoxide dismutase (SOD) activity than other equine tissues, which makes them
      inherently more vulnerable to damage induced by reactive oxygen species (ROS)
      produced by neutrophils that enter the tissues. In the advanced clinical stages
      of acute laminitis, pathologic events in affected feet include a breakdown in the
      basement membrane, neutrophil infiltration, and platelet-neutrophil aggregates in
      laminar dermal veins, highlighting the contribution of neutrophils to the
      pathophysiology of the disease. The aim of this study was to determine the role
      of p38 MAPK in the mechanism underlying equine neutrophil migration to
      potentially reveal therapeutic targets that may limit lamellar damage from the
      neutrophil influx that occurs in acute laminitis. We determined that the
      endogenous chemoattractant LTB(4) transiently activated p38 MAPK and induced
      chemotaxis of equine primary neutrophils. Inhibition with the p38 MAPK specific
      inhibitor SB203580 reduced LTB(4)-induced migration in a dose-dependent manner
      with an IC(50) of 2.8 microM. We then examined the potential mechanisms
      underlying the ability of SB203580 to abolish migration. We determined that
      inhibition of p38 MAPK with 10 microM SB203580 disrupted the ability of
      neutrophils to polarize in response to LTB(4) and PAF. In contrast, p38 MAPK did
      not appear to be required for chemoattractant- or PKC-induced beta2 integrin
      dependent adhesion or chemoattractant-induced upregulation of surface beta2
      integrins, but was required for TNFalpha-induced adhesion. These findings support
      a function for p38 MAPK in equine neutrophil migration and suggest the potential
      for the ability of p38 MAPK inhibition to limit neutrophilic inflammation in the
      laminae during acute laminitis.

PMID- 19095310
TI  - The use of piperacillin-tazobactam coated tympanostomy tubes against
      ciprofloxacin-resistant Pseudomonas biofilm formation: an in vitro study.
AB  - BACKGROUND AND OBJECTIVE: Bacterial biofilm formation has been implicated in the
      high rate of persistent otorrhea after tympanostomy tube insertion. It has been
      suggested that the tube material may be an important factor in the development of
      otorrhea. Recently we reported the presence of ciprofloxacin-resistant
      Pseudomonas aeruginosa (CRPA) biofilms on infected tympanostomy tubes following
      the use of intractable post-tympanostomy tubes and the onset of otorrhea. In this
      study, we have evaluated the resistance of piperacillin-tazobactam coated with
      chitosan on a tympanostomy tube to prevent CRPA biofilm formation in vitro.
      MATERIALS AND METHODS: Three sets each of piperacillin-tazobactam coated silicone
      tubes (n=5), commercial silver-oxide coated silicone tubes (Activent, Silic)
      (n=5) and control uncoated tympanostomy tubes (Paparella type 1) (n=5) were
      processed for evaluation. The piperacillin-tazobactam coated tympanostomy tubes
      were compared with the silver-oxide coated tubes and the uncoated control tubes
      for resistance to CRPA biofilm formation after in vitro incubation. RESULTS:
      Scanning electron microscopy showed that the surface of the silver-oxide coated
      tube (Activent) formed a thick biofilm with crusts as well as an uncoated tube.
      In contrast, the surface of a piperacillin-tazobactam coated tympanostomy tube
      showed virtually no CRPA biofilm formation. CONCLUSION: The piperacillin
      tazobactam coated tympanostomy tube showed resistance to CRPA biofilm formation.
      The piperacillin-tazobactam coating may be useful to reduce CRPA biofilm
      formation; however, further in vivo studies are necessary.

PMID- 19095311
TI  - Toxicity of the pharmaceutical clotrimazole to marine microalgal communities.
AB  - Clotrimazole belongs to the group of 14alpha-demethylase inhibiting fungicides.
      It is widely used in human and veterinary medicine and has been identified as a
      priority pollutant for the marine environment. However, the toxicity of
      clotrimazole to marine primary producers is largely unknown. We therefore sampled
      natural microalgal communities (periphyton) and exposed them to concentration
      series of clotrimazole over 4 days. 50 pmol/L clotrimazole caused a concentration
      dependent accumulation of C14alpha-methylated sterol precursors, which coincided
      with a decrease in algal-specific C14-desmethyl sterols. This indicates an
      inhibition of algal 14 alpha-demethylases already at environmental
      concentrations. A clotrimazole concentration of 500 pmol/L reduced total sterol
      content to 64% of control level. Community chlorophyll a content was affected by
      clotrimazole in a bi-phasic manner with first reductions becoming visible at 500
      pmol/L, along with indications of an altered cycling of photoprotective
      xanthophyll pigments. Concentrations of 10-100 nmol/L and higher caused large
      reductions in community growth, and changed community pigment profiles in a
      concentration-dependent monotonous manner. The study further indicated that
      diatoms use obtusifoliol as a natural substrate for 14alpha-demethylase, just as
      higher plants do but also utilize norlanosterol.

PMID- 19095312
TI  - Factors affecting institutionalization in older Hong Kong Chinese patients after
      recovery from acute medical illnesses.
AB  - Older patients with medical illnesses are at risk of institutionalization. The
      purpose of this study is to investigate the factors leading to
      institutionalization in older patients after recovery from medical illnesses. We
      studied 535 older patients in two convalescence hospitals in Hong Kong. Of them,
      116 patients (21.7%) needed to move to nursing homes upon discharge. Univariate
      analysis showed that age, single/divorced/widowed status, longer length of stay,
      pressure sores, urinary incontinence, urinary catheterization, falls, dementia,
      diabetes mellitus, Barthel index (100), Elderly Mobility Score (EMS), Chinese
      version of the mini-mental state examination (C-MMSE) and albumin levels were
      significant factors associated with institutionalization. Multivariate analysis
      showed that being single/divorced/widowed (odds ratio=OR=2.74, 95% confidence
      interval=CI=1.36-5.53, p=0.0048), having urinary incontinence on discharge
      (OR=5.13, CI=2.66-10.6, p<0.001) and admission due to falls (OR=2.4, CI=1.03
      5.57, p=0.04) were independent risk factors for nursing home admission. Higher
      admission EMS (OR=0.91, CI=0.84-0.97, p=0.009), admission C-MMSE (OR=0.93,
      CI=0.87-0.98, p=0.019), and discharge albumin levels (OR=0.93, CI=0.88-0.99,
      p=0.02) were independent protecting factors against nursing home admission.
      Knowledge of these factors can allow us to predict accommodation outcome and
      develop intervention strategy to reduce institutionalization in the older
      patients.

PMID- 19095313
TI  - The process and organizational characteristics of memory clinics in Israel in
      2007.
AB  - We previously described the characteristics and activities of 25 memory clinics
      in Israel in 1998 using a mail survey. Questionnaires assessing the
      administrative structure of the clinics, patient characteristics, processes and
      methods used, and outcomes of the assessment were mailed again in 2007 to 35
      memory clinics. Overall, the general operating characteristics of the clinics in
      2007 were found to be similar to those reported in the previous survey conducted
      in 1998. The assessment process in 2007 was shorter than in 1998 (mean time=1.92
      and 3.12 h, respectively), although both surveys were based on an
      interdisciplinary team, including a physician, a nurse and a social worker.
      However, in 2007 the teams were more wide-ranging. A wider variety of instruments
      were reported in the more recent survey. Most of the clinics in both surveys
      reported that family members were involved at all stages of the assessment.
      Medication treatment was the main outcome reported by the clinics in both
      surveys. There has been a development in the process and organizational
      characteristics of memory clinics in Israel over the years, probably as a
      consequence of the development of knowledge in the area of cognitive
      deterioration.

PMID- 19095314
TI  - The factorial structure of the mini mental state examination (MMSE) in
      Alzheimer's disease.
AB  - Our aim was to evaluate the factorial structure of the mini mental state
      examination (MMSE) in Alzheimer's disease (AD). Five hundred and twenty-four
      consecutive outpatients at their first diagnostic work-up (age 78.02+/-6.07
      years, education 6.62+/-3.48 years, mean MMSE score 20.23+/-4.89) (+/-S.D.) with
      probable AD (based on DSM-IV and NINCDS-ADRDA criteria) were enrolled in a
      multicenter, cross-sectional, regional-based study. For the purpose of the
      present study, the 11 subtests composing the MMSE and the global MMSE score
      (ranging from 10 to 29, included) were considered. Factor analysis with Varimax
      rotation method identified two factors that explained about the 85% of total
      variance. The first factor explained the 65% of variance and mainly included
      temporal orientation, delayed recall, attention/concentration, and constructional
      praxia. The second factor explained the 20% of variance and included reading a
      sentence, writing a sentence, naming, verbal repetition and immediate memory. The
      first factor was a reliable index of cognitive deterioration along the MMSE score
      interval between 29 and 10, whereas the second factor was not a suitable marker
      in this range. The two-factor structure of the MMSE in AD is shown in a large
      series of patients. The first factor expresses the ability to use new information
      and is related with working memory. The second factor is related with a more
      consolidated knowledge, namely verbal abilities, and is essentially useless in
      mild to moderate AD.

PMID- 19095315
TI  - Can an individualized and comprehensive care strategy improve urinary
      incontinence (UI) among nursing home residents?
AB  - Urinary incontinence (UI) is one of the most common and distressing conditions
      among nursing home residents. Although scheduled care is usually provided for
      them, incontinence care should be individualized regarding going to the toilet,
      changing diapers, and taking food and water. We have developed an individualized
      and comprehensive care strategy to address the problem. We conducted an
      intervention study that involved training chiefs of staffs, who in turn trained
      other staffs, and encouraging residents. A total of 153 elderly subjects selected
      from 1290 residents in 17 nursing homes were eligible to receive our
      individualized and comprehensive care. The goals of the care strategy were (i) to
      complete meal intake; (ii) to take fluids up to 1500 ml/day; (iii) to urinate in
      a toilet; (iv) to spend over 6h out of bed; and (v) to reduce time spent in wet
      diapers. We explained the aims of our strategy to the chiefs of staff of each
      nursing home and instructed them to encourage residents to take an active part in
      our individualized and comprehensive care strategy for 12 weeks. For 3 days
      before and after that period, we assessed the changes in fluid volume intake,
      time spent in wet diapers, size of diaper pads, and urination habits. The result
      was that fluid volume intake significantly increased (p<0.001) while time spent
      in wet diapers decreased (p<0.001). The number of residents wearing diapers
      decreased as did the size of pads during the day (p=0.0017). The proportion of
      residents using diapers at night was reduced and those using toilets at night
      increased (p=0.007). This study suggests that such an individualized and
      comprehensive care strategy can offer a measurable improvement in UI care.

PMID- 19095316
TI  - Long-term prognostic importance of resting heart rate in patients with left
      ventricular dysfunction in connection with either heart failure or myocardial
      infarction: the DIAMOND study.
AB  - BACKGROUND: Elevated resting heart rate is associated with increased mortality in
      a variety of cardiac diseases, but comparisons between different clinical
      settings are lacking. We investigated the long-term prognostic importance of
      resting heart rate in patients hospitalized with left ventricular dysfunction in
      connection with either heart failure (HF) or myocardial infarction (MI). METHODS:
      In the Danish Investigations and Arrhythmia ON Dofetilide (DIAMOND) study;
      patients with left ventricular dysfunction were randomized to Dofetilide (class
      III antiarrhythmic drug) or placebo. One part of the study enrolled 1518 patients
      with HF and another 1510 patients with MI. Mortality analyses were performed
      using multivariable adjusted Cox proportional hazard models. RESULTS: During 10
      years of follow-up, 1076 (72%) patients with MI and 1336 (89%) patients with HF
      died. In multivariable adjusted models, every increment in baseline heart rate of
      10 bpm was associated with an increase in mortality in both MI-patients (hazard
      ratio, 1.14; 95%-confidence interval (CI): 1.09-1.19; P<.0001) and HF-patients
      (hazard ratio, 1.10; CI: 1.06-1.15; P<.0001). The importance of resting heart
      rate on short-term prognosis was stronger in the MI patients compared to the HF
      patients (P<.0001 for interaction). There was no interaction between heart rate
      and beta-blockade, and inclusion of beta-blockade in the model did not change the
      results. CONCLUSIONS: Resting heart rate was independently associated with
      increased risk of overall mortality. The prognostic importance of resting heart
      rate is stronger in patients with MI compared to patients with HF, especially in
      the short term.

PMID- 19095317
TI  - Over-expression of hepatocyte growth factor in smooth muscle cells regulates
      endothelial progenitor cells differentiation, migration and proliferation.
AB  - BACKGROUND: Endothelial repair is one of key events after vascular injury. The
      mechanisms by which hepatocyte growth factor (HGF) and endothelial progenitor
      cells (EPCs) may be responsible for re-endothelialization of injured blood vessel
      wall are poorly understood. METHODS: Primary culture SMCs were transfected with
      pcDNA3.0-HGF followed by G418 selection, one of G418-resistant colonies in well
      was picked, propagated and used as donor cells for further experiments. HGF and
      VEGF expression in SMCs were detected with western blot and enzyme linked
      immunosorbent assays (ELISA). Rat EPCs were cultured in untreated, pcDNA3.0 and
      pcDNA3.0-HGF transfected SMCs conditioned medium with or without anti-VEGF or
      exogenous recombinant HGF addition. eNOS, KDR and CD31 expression in EPCs was
      determined by real-time quantitative polymerase chain reaction (RT-qPCR) or flow
      cytometry; EPCs migration and proliferation were measured by using a modified
      Boyden chambers and MTT assay respectively. RESULTS: Abundant and stable
      expression of HGF was found in G418-resistant colony-derived SMCs. VEGF
      expression significantly increased in HGF transfected SMCs. Exogenous recombinant
      HGF (rHGF) markedly up-regulated eNOS mRNA expression in EPCs and promoted EPCs
      migration and proliferation, but no significant changes were found in KDR and
      CD31 mRNA expression. HGF transfection in SMCs was more effective than exogenous
      HGF for EPCs differentiation, proliferation and migration. CONCLUSIONS: Over
      expression of HGF in SMCs can be helpful for promoting EPCs differentiation,
      increasing EPCs migration and proliferation. It may be responsible for
      angiogenesis of arteriosclerosis lesions and useful for blood vessel tissue
      engineering.

PMID- 19095318
TI  - Diagnosis of pleuritic chest pain query PE: beware of dissecting thoracic
      aneurysm of aorta.

PMID- 19095319
TI  - In- and outpatients with noncompaction: differences in cardiac and neuromuscular
      co-morbidity.
AB  - BACKGROUND AND METHODS: The prognosis of patients with left ventricular
      hypertrabeculation/noncompaction (LVHT) is controversial. LVHT is associated with
      neuromuscular disorders (NMD) and diagnosed echocardiographically in in- as well
      as outpatients. We compared cardiologic and neurologic findings and mortality in
      LVHT-patients according to their diagnosis established as in- or outpatients.
      RESULTS: Among 113 patients (33 females, mean-age 53 years), 91 were investigated
      neurologically. Fifty-nine inpatients were older (55 versus 50 years, p<0.05),
      more frequently referred because of heart failure (73 versus 37%, p<0.001), had
      more often diabetes (24 versus 7%, p<0.05), heart failure (81 versus 57%,
      p<0.01), a lower left-ventricular fractional-shortening (21 versus 26%, p<0.05)
      and more extensive LVHT (1.7 versus 1.5 affected walls, p<0.05). Fifty-four
      outpatients were referred more often because of chest-pain (33 versus 12%,
      p<0.01), myopathy (13 versus 2%, p<0.05), were more often neurologically normal
      (20 versus 7%, p<0.05) or had a specific NMD (28 versus 12%, p<0.05). During a
      mean follow-up of 3.8 years, mortality was 5.8%/year. Inpatients had a higher
      mortality (12.1 versus 2.1%/year, p=0.0002) and a shorter time between LVHT
      diagnosis and death (1.7 versus 4.6 years, p=0.0197) than outpatients.
      CONCLUSIONS: Outpatients with LVHT have a better prognosis than inpatients.
      Inpatients with LVHT should be closely monitored.

PMID- 19095320
TI  - Prevention of stroke by percutaneous left atrial appendage closure: short term
      follow-up.
AB  - Preliminary studies suggest that left atrial appendage (LAA) closure might be
      beneficial in the prevention of stroke in patients with atrial fibrillation (AF).
      We evaluated the preliminary clinical efficacy of percutaneous LAA closure using
      the PLAATO-device (ev3 Endovascular, Inc., North Plymouth, MN) and found that
      none of the patients suffered from thrombo-embolic events within a time period of
      2 years after successful LAA closure. Therefore, we believe that percutaneous
      closure of the LAA might be a valuable technique for AF patients with contra
      indications for or failure of oral anticoagulation to prevent thrombo-embolic
      events.

PMID- 19095321
TI  - Femoral pseudoaneurysms and current cardiac catheterization: evaluation of risk
      factors and treatment.
AB  - OBJECTIVES: We sought to determine the incidence of femoral pseudoaneurysm (FPA)
      following cardiac catheterization, identify the risk factors for FPA and factors
      influencing therapeutic strategy. METHODS: 11,992 consecutive patients who
      underwent cardiac catheterization via femoral artery were studied over a period
      of four years in one University Hospital. Our prospective case control group
      analysis registered patients who developed FPA after the procedure. Patient
      related factors, procedure related factors and peri-procedure treatment were
      compared between the two groups. RESULTS: 76 FPA were diagnosed over the study
      period accounting for a global incidence of 0.6% procedures. By univariate
      analysis, interventional procedure (p<0.01), rhythmologic procedure (p=0.03),
      sheath>or=6F (p=0.04) and left groin puncture (p<0.001) were FPA risk factors. By
      multivariate analysis, interventional procedure (adjusted odds ratio [OR]=1.99;
      95% confidence interval [CI]1.14-3.44 p=0.01) and left groin puncture (OR=4.65;
      95% CI, 1.78-12.1 p=0.001) are independent predictive factors of FPA. FPA
      thrombosis was obtained by ultrasound guided compression (UGC) in 71% of the
      cases. By univariate analysis, PFA diameter larger than 4 cm (p<0.001), the use
      of anticoagulation (p<0.01) or GPIIbIIIa inhibitors (p=0.001) and UGC under
      anticoagulation (p=0.01) are predictive factors of need for FPA surgical repair.
      By multivariate analysis, FPA diameter>4 cm and use of GPIIbIIIa inhibitors are
      independent predictive factors of FPA's surgical treatment. Superficial femoral
      puncture was predictive of successful UGC both by uni and multivariate analysis.
      CONCLUSIONS: Our study shows that FPA occurrence is mainly due to by procedure
      related factors. FPA size, level of puncture and the use of GPIIbIIIa inhibitors
      are independent predictive factors of need for surgical therapy.

PMID- 19095323
TI  - Anatomical bases for the radiological delineation of lymph node areas. Part III:
      Pelvis and lower limbs.
AB  - Cancer spreads locally through direct infiltration into soft tissues, or at a
      distance by invading vascular structures, then migrating through the lymphatic or
      blood flow. Although cancer cells carried in the blood can end in virtually any
      corner of the body, lymphatic migration is usually stepwise, through successive
      nodal stops, which can temporarily delay further progression. In radiotherapy,
      irradiation of lymphatic paths relevant to the localization of the primary has
      been common practice for decades. Similarly, excision of cancer is often
      completed by lymphatic dissection. Both in radiotherapy and in surgery, advanced
      knowledge of the lymphatic pathways relevant to any tumor location is an
      important information for treatment preparation and execution. The third part of
      these series describes the lymphatics of the pelvis and the lower limb. It
      Provides anatomical bases for the radiological delineation of lymph nodes areas
      in the pelvic cavity and in the groin. It also offers the first original
      classification for labeling the intrapelvic nodes, grouped in seven paired
      volumes (called levels I-VII), functionally linked with one another and lower
      abdominal levels by eight potential drainage pathways.

PMID- 19095324
TI  - Characterisation of non-pathogenic Yersinia pseudotuberculosis-like strains
      isolated from food and environmental samples.
AB  - Non-pathogenic Yersinia pseudotuberculosis-like strains were recovered from
      Finnish food and environmental samples. These strains could not be differentiated
      from Y. pseudotuberculosis strains using API 20E or other phenotypical tests.
      However, all of the strains were inv-, and virF-negative with polymerase chain
      reaction (PCR), while all Y. pseudotuberculosis strains used as controls were inv
      positive and fresh Y. pseudotuberculosis strains were also virF-positive,
      indicating that the Y. pseudotuberculosis-like strains were non-pathogenic. Using
      pulsed-field gel electrophoresis (PFGE) with NotI enzyme and ribotyping with
      EcoRI and HindIII enzymes, the Y. pseudotuberculosis-like strains, which grouped
      genetically together, could be differentiated from true Y. pseudotuberculosis
      strains and from strains belonging to other sucrose-negative Yersinia species. In
      addition, the O-antigen gene cluster of one Y. pseudotuberculosis-like strain was
      characterized, and it differed from those of known Y. pseudotuberculosis
      serotypes. This study demonstrates that identification of Y. pseudotuberculosis
      from food and environmental sources using solely biochemical reactions can be
      incorrect, and when a strain cannot be serotyped to known Y. pseudotuberculosis
      serotypes, the pathogenic potential of isolates should be determined.

PMID- 19095325
TI  - Enhanced expressions of sodium-glucose cotransporters in the kidneys of diabetic
      Zucker rats.
AB  - Diabetes-mediated changes in mRNA expressions of kidney glucose transporters
      SGLT1 and SGLT2 were investigated in Zucker rats. SGLTs expressions in pre
      diabetic obese rats were similar to leans. SGLT1 and SGLT2 levels in diabetic
      obese rats were 1.6 (P<0.03) and 4.8 (P<0.002) folds higher than age-matched
      leans, respectively.

PMID- 19095326
TI  - Immediate impact of a diabetes training programme for primary care physicians--an
      endeavour for national capacity building for diabetes management in India.
AB  - AIMS: India faces a huge burden from diabetes. National capacity for management
      of diabetes has to be strengthened by improving knowledge of physicians treating
      diabetes, especially in semi urban and rural areas. A training programme was
      formulated and conducted at national level, as a step towards this goal. METHODS:
      Physicians from 6 states of India (n=3023, M:F 2311:712), aged 30-55 years, with
      service of >or=3 years, (government n=1720, private n=1303, semi urban and rural
      areas (n=1581:1442)) were trained in diabetes care in 5-day workshops between
      March 2004 to December 2006. Impact of training was assessed by pre- and post
      training knowledge scores, feedback on usefulness of training modules,
      prioritizing activities to be introduced in their practice and methods to be used
      for raising public awareness on diabetes. RESULTS: The training significantly
      improved knowledge on treatment, complications, pathophysiology and diagnosis of
      diabetes (p<0.001). The participants considered information on preventive aspects
      of diabetes and foot care as highly educative. Patient education and team
      training were considered important in diabetes management. Interest was evinced
      in raising public awareness about the disease. CONCLUSIONS: Well-planned short
      training programmes are useful in improving knowledge and in creating enthusiasm
      to improve diabetes care and awareness.

PMID- 19095327
TI  - Phase II study of oral vinorelbine in combination with carboplatin followed by
      consolidation therapy with oral vinorelbine as single-agent in unresectable
      localized or metastatic non-small cell lung carcinoma.
AB  - INTRODUCTION: This phase II study assessed the efficacy and safety of oral
      vinorelbine given weekly in combination with carboplatin (CBDCA) AUC 5 once every
      3 weeks for four cycles in chemonaive patients with advanced non-small cell lung
      carcinoma (NSCLC), followed by consolidation therapy with single-agent oral
      vinorelbine in non-progressive patients. METHODS: Chemonaive advanced NSCLC
      patients received four cycles of combination therapy with CBDCA AUC 5 day 1 and
      oral vinorelbine, 60 mg/m2 on days 1, 8 and 15 (cycle 1), dose increased to 80
      mg/m2 (cycles 2-4) in absence of grades 3-4 neutropenia (NCI-CTCv2).
      Consolidation therapy with oral vinorelbine was continued (cycle 5) at same
      dosage; if dose was decreased during combination therapy, it was given at 60
      mg/m2, then increased at 80 mg/m2 (cycle 6) in absence of grades 3-4 neutropenia
      until PD, toxicity or patient's refusal. RESULTS: A total of 57 patients were
      registered and 56 patients were treated (ITT population), median age was 61 years
      (37-71). Objective response evaluated by RECIST was 17.9% (95% confidence
      interval, CI [8.9-30.4]) and disease control (CR, PR, NC) 73.2% (95% CI [59.7
      84.2]), median progression-free survival 4.3 months (95% CI [3.1-5.1]) with
      median overall survival 9.7 months (95% CI [7.7-11.9]) and 1-year survival 37.1%
      (95% CI [24.4, 49.9]). Grades 3-4 neutropenia occurred in 67.9% of patients
      during combination and 20% during consolidation; febrile neutropenia occurred in
      4 patients (7.1%) during combination therapy. Non-hematological toxicities
      occurred primarily during combination (grade 3 nausea and grade 3 vomiting in
      7.1% of patients). CONCLUSIONS: The combination of oral vinorelbine given weekly
      in 3-week cycles in combination with carboplatin followed by consolidation
      therapy with oral vinorelbine as a single-agent was able to achieve efficacy
      results in line with other doublets including carboplatin in terms of response as
      well as survival. This regimen reported a good profile of tolerability in the
      treatment of advanced NSCLC, allowing that this combination can be easily
      proposed for the palliative care of NSCLC patients where the advantages of
      carboplatin over cisplatin are still appreciated.

PMID- 19095328
TI  - Enhanced biodegradation by hydraulic heterogeneities in petroleum hydrocarbon
      plumes.
AB  - In case of dissolved electron donors and acceptors, natural attenuation of
      organic contaminant plumes in aquifers is governed by hydrodynamic mixing and
      microbial activity. Main objectives of this work were (i) to determine whether
      aerobic and anaerobic biodegradation in porous sediments is controlled by
      transverse dispersion, (ii) to elucidate the effect of sediment heterogeneity on
      mixing and biodegradation, and (iii) to search for degradation-limiting factors.
      Comparative experiments were conducted in two-dimensional sediment microcosms.
      Aerobic toluene and later ethylbenzene degradation by Pseudomonas putida strain
      F1 was initially followed in a plume developing from oxic to anoxic conditions
      and later under steady-state mixing-controlled conditions. Competitive anaerobic
      degradation was then initiated by introduction of the denitrifying strain
      Aromatoleum aromaticum EbN1. In homogeneous sand, aerobic toluene degradation was
      clearly controlled by dispersive mixing. Similarly, under denitrifying
      conditions, microbial activity was located at the plume's fringes. Sediment
      heterogeneity caused flow focusing and improved the mixing of reactants.
      Independent from the electron accepting process, net biodegradation was always
      higher in the heterogeneous setting with a calculated efficiency plus of 23-100%
      as compared to the homogeneous setup. Flow and reactive transport model
      simulations were performed in order to interpret and evaluate the experimental
      results.

PMID- 19095329
TI  - Genotype-dependent expression of specific members of potato protease inhibitor
      gene families in different tissues and in response to wounding and nematode
      infection.
AB  - Protease inhibitors (PIs) are small ubiquitous proteins with a variety of
      biological functions in plants, including protein stabilization, modulation of
      apoptosis and defense against pathogens. Kunitz-like inhibitors (PKPIs) and
      proteinase inhibitors 1 (PI-1) are abundant in storage organs of potato plants
      and are up-regulated in other tissues in response to biotic and abiotic stress.
      However, little information is available on genotype-dependent regulation of
      individual PKPI group- and PI-1 genes. We isolated, sequenced and characterized
      four novel full-length PI-1 cDNAs (PPI3A2, PPI3A4, PPI2C4 and PPI2C1A) from
      Solanum tuberosum cv. Desiree. Specific primers were developed for PI-1 genes
      PPI3A2, PPI3B2 and PPI2C4 and the three PKPI homology groups A, B and C. Their
      expression profiles were studied by semi-quantitative RT-PCR in comparison with
      transcripts of the PI-1, Pin2 and PR1 gene families in various tissues, after
      wounding and Globodera rostochiensis infection of nematode-resistant genotypes
      P40 and LB7/4/c-I-7, and susceptible cv. Desiree. Individual PI-1 genes and PKPI
      homology groups were expressed in a tissue- and genotype-dependent manner after
      wounding and nematode infection. The differences in PI expression patterns were
      related to the intensity, type of inhibitors produced, and the kinetics of
      induction. Therefore, different genotype-environment combinations produce
      different sets of PI transcripts. Potato plants reacted to G. rostochiensis
      infection by modulating PKPI, PI-1 and Pin2, but not PR1 gene expression,
      suggesting that the jasmonic acid but not the salicylic acid defense signaling
      pathway is activated. PI expression profiles were not correlated with the
      resistance status of the potato genotype infected with G. rostochiensis.

PMID- 19095330
TI  - Factors affecting compliance with glove removal after contact with a patient or
      environment in four intensive care units.

PMID- 19095331
TI  - [Indications of vitamin K antagonists and aspirin in the atrial fibrillation of
      the elderly].
AB  - Non valvular atrial fibrillation is a public health concern because of the
      frequency and the severity of its embolic complications, particularly strokes.
      The aim of this paper is to analyze the recent recommendations for the prevention
      of embolic events and their application in the elderly. The recommendations for
      the prevention of stroke, published in 2001 on the basis of the results of
      randomized studies comparing vitamin K antagonists (VKA) and aspirin versus
      placebo, have been modified in August 2006. VKA are recommended in patients at
      high risk of stroke. In patients considered at moderate risk, the choice is now
      possible between VKA and aspirin, with a reduced dosage of aspirin (75 to 325
      mg). The absolute risk of stroke related to age, hypertension, heart failure or
      diabetes is not yet evaluated. Further studies would be necessary in order to
      precise the recommendations for patients with only one of these risk factors:
      aspirin or VKA? In geriatric patients with several risk factors, VKA are under
      prescribed. A better knowledge of the embolic risk of atrial fibrillation, of the
      often overestimated hemorrhagic risk of VKA, of the quite underestimated
      hemorrhagic risk of aspirin and of the recommendations for prevention would be
      necessary.

PMID- 19095332
TI  - [An umbilical nodule and a periungeal hallux ulceration].

PMID- 19095333
TI  - Late onset of abducens palsy after Le Fort I maxillary osteotomy.
AB  - Abducens nerve palsy after low-level Le Fort 1 maxillary osteotomy is a rare
      complication, but with few cases reported, its true incidence is not known. We
      report an unusual case of late postoperative onset of abducens palsy that differs
      from existing case reports.

PMID- 19095334
TI  - Health-care professionals' views about safety in maternity services: a
      qualitative study.
AB  - OBJECTIVE: to explore health-care professionals' views about safety in maternity
      services. This paper identifies aspects of care that are less safe than they
      should be, possible ways to improve safety, and potential obstacles to achieving
      these improvements. This study was part of the King's Fund inquiry into the
      safety of maternity services in England. DESIGN: qualitative study with a sample
      of health-care professionals who work in maternity services and who responded to
      the call for evidence. Data were collected by questionnaire and analysed using
      thematic content analysis. SETTING: maternity professionals throughout England
      were invited to take part. PARTICIPANTS: midwives, obstetricians, student
      midwives, nurses, neonatal nurses, general practitioners, managers, hospital
      doctors and paediatricians. In total, there were 591 respondents. MEASUREMENTS
      AND FINDINGS: participants were asked to respond to open-ended questions
      identifying aspects of maternity care that were less safe than they should be,
      potential solutions to improve safety of care, and any barriers to implementing
      these improvements. Problems described included the increasing social and medical
      complexity of the pregnant population, low staffing levels, inappropriate skill
      mix, low staff morale, inadequate training and education, medicalisation of
      birth, poor management, lack of resources and reconfiguration. Proposed solutions
      included more staff, better teamwork and skill mix, improved training, more one
      to-one care, caseloading, better management, more resources, better guidelines
      and learning from incidents. Barriers to implementing improvements included
      stressed staff who were resistant to change, inadequate management/poor staff
      management relationships and financial restraints. KEY CONCLUSIONS: the responses
      of maternity professionals convey a deep sense of staff anxiety regarding how the
      problems they face pose a threat to safety. IMPLICATIONS FOR PRACTICE: policy
      makers and professional bodies need to take the concerns expressed by staff
      seriously. Concerted efforts are required to improve maternity services and
      support maternity professionals.

PMID- 19095335
TI  - Toxicity biomarker expression in daphnids exposed to manufactured nanoparticles:
      changes in toxicity with functionalization.
AB  - In previous work we have shown that the toxicity of nanomaterials to Daphnia spp.
      differs with the type of nanoparticle either due to the core of the particle or
      to the way in which a particle suspension is prepared. The purpose of this study
      was to investigate the toxicity and antioxidant response of Daphnia pulex in
      relation to a change in surface functionalization of nanomaterials with the same
      core material, nC60. Despite the lack of acute toxicity for various nC60
      suspensions up to 100 ppm concentration, there was a significant production of
      the toxicity biomarkers glutathione-S-transferase and catalase, at lower
      concentrations indicating changes in reactive oxygen species. Nanoparticle
      functionalization significantly affected this response. Oxidative stress markers
      appear to be a good predictor of potential future toxicity of nanomaterials.
      Functionalization alters both toxicity and oxidative stress in whole organism
      assays.

PMID- 19095336
TI  - Even low to medium nitrogen deposition impacts vegetation of dry, coastal dunes
      around the Baltic Sea.
AB  - Coastal dunes around the Baltic Sea have received small amounts of atmospheric
      nitrogen and are rather pristine ecosystems in this respect. In 19 investigated
      dune sites the atmospheric wet nitrogen deposition is 3-8kg Nha(-1)yr(-1). The
      nitrogen content of Cladonia portentosa appeared to be a suitable biomonitor of
      these low to medium deposition levels. Comparison with EMEP-deposition data
      showed that Cladonia reflects the deposition history of the last 3-6 years. With
      increasing nitrogen load, we observed a shift from lichen-rich short grass
      vegetation towards species-poor vegetation dominated by the tall graminoid Carex
      arenaria. Plant species richness per field site, however, does not decrease
      directly with these low to medium N deposition loads, but with change in
      vegetation composition. Critical loads for acidic, dry coastal dunes might be
      lower than previously thought, in the range of 4-6kg Nha(-1)yr(-1) wet
      deposition.

PMID- 19095337
TI  - Informed consent in biobank research: a deliberative approach to the debate.
AB  - As acknowledged in the literature, public consultation related to biobanks has
      been largely oriented to assuring and informing rather than seeking considered
      input. In April and May of 2007, the authors participated in running a
      deliberative public engagement event in British Columbia, Canada, which sought to
      enhance public input related to the governance of biobanks. The topic of the
      event was 'Biobanking in British Columbia (BC)' and at the event a random-digit
      dialed demographically stratified sample of 21 participants deliberated on what
      values and interests ought to be considered in the regulation and use of biobanks
      for health research. In this paper, we report results related to debate over the
      place of informed consent in biobank research. Drawing on a pre/post-survey and
      qualitative analysis of event transcripts, we show that participants indicated
      strong support for biobanks, for a general reduction in concern for withdrawal of
      samples, and placed a strong emphasis on the need for review of biobanks research
      that is independent of funders and researchers. In this context, there was
      persistent disagreement about when consent was required for new research
      activities.

PMID- 19095338
TI  - Global variations in health: evaluating Wilkinson's income inequality hypothesis
      using the World Values Survey.
AB  - This international comparative study analyses individual-level data derived from
      the World Values Survey to evaluate Wilkinson's [(1996). Unhealthy societies: The
      afflictions of inequality. London: Routledge; (1998). Mortality and distribution
      of income. Low relative income affects mortality [letter; comment]. British
      Medical Journal, 316, 1611-1612] income inequality hypothesis regarding
      variations in health status. Random-coefficient, multilevel modelling provides a
      direct test of Wilkinson's hypothesis using micro-data on individuals and macro
      data on income inequalities analysed simultaneously. This overcomes the
      ecological fallacy that has troubled previous research into links between
      individual self-rated health, individual income, country income and income
      inequality data. Logic regression analysis reveals that there are substantial
      differences between countries in self-rated health after taking account of age
      and gender, and individual income has a clear effect in that poorer people report
      experiencing worse health. The Wilkinson hypothesis is not supported, however,
      since there is no significant relationship between health and income inequality
      when individual factors are taken into account. Substantial differences between
      countries remain even after taking account of micro- and macro-variables; in
      particular the former communist countries report high levels of poor health.

PMID- 19095339
TI  - Weighing the importance of neighbourhood: a multilevel exploration of the
      determinants of overweight and obesity.
AB  - Overweight and obesity have reached epidemic proportions in many countries,
      including Canada. In addition to becoming critical public health challenges in
      and of themselves, they represent major risk factors for chronic disease and
      disability (e.g. cardiovascular disease, diabetes). The various symptoms and co
      morbidities associated with these chronic conditions place tremendous stress on
      the Canadian health care system, generating economic concern. This research takes
      a population health approach to the study of obesity, examining the complex
      relationships between individual demographics and behaviours, and aspects of the
      local social and physical environments. A subset of a nationally representative
      survey was linked to neighbourhood-level data from the 1991 Canadian Census, and
      analysed from a multilevel perspective. This study found substantial area-level
      variation in body mass index and waist circumference, and discovered an important
      role for neighbourhood-level characteristics independent of individual-level
      characteristics. These findings provide evidence that the underlying mechanisms
      driving the increasing prevalence of overweight and obesity may be so called
      obesogenic environments that encourage physical inactivity and unhealthy eating.
      An effective policy response must address environmental conditions in order to
      curb current obesity trends.

PMID- 19095341
TI  - Investigating the medical forensic examination from the perspectives of sexually
      assaulted women.
AB  - Across many jurisdictions, a key institutional response to sexual assault is
      centred on the collection of medico-legal evidence through a medical forensic
      examination (MFE). Despite the increased routinization of this practice, such
      evidence often is not related to positive criminal justice outcomes. As there has
      been little systematic investigation of the perspectives of victims regarding the
      MFE, we conducted semi-structured, face-to-face interviews with 19 women aged 17
      46 years who had been sexually assaulted and had undergone an MFE in the previous
      six months at one of four specialized hospital-based sexual assault centres in
      Ontario, Canada. Extracts from the transcribed interviews were coded into two
      broad themes, 'Expectations' and 'Experiences', from which a series of lower
      order constructs were derived. We found that most women went to a centre to have
      their physical and emotional needs addressed rather than medico-legal evidence
      collected and were overwhelmingly satisfied with their interactions with
      specially trained nurse examiners. However, some women were confused about the
      purpose of the MFE, believing that their access to treatment hinged upon
      undergoing this process. Moreover, though optional, several indicated that they
      had been instructed to have an MFE by the police and/or nurse examiner. Most
      women who chose to have evidence collected did so with the hope that it would
      hold the assailant accountable and generate social recognition of the harm done
      to them. While many stated that they were distressed during the MFE, some
      reported feeling simultaneously empowered by the fact that the experience
      fostered a "sense of doing something". These findings point to the value of
      collecting medico-legal evidence in settings staffed with supportive
      practitioners who also attend to women's health related concerns. Implications
      with respect to issues of informed consent, revictimization, and empowerment, as
      well as the relative weight given to the MFE in the post-sexual assault care
      encounter, are discussed.

PMID- 19095342
TI  - Restoration survival within the general dental services in England and Wales.
      Introduction.

PMID- 19095340
TI  - Discrimination and health among Asian American immigrants: disentangling racial
      from language discrimination.
AB  - We examined whether self-reported discrimination based on race and language was
      associated with the number of chronic health conditions among Asian American
      immigrants. We also examined whether these relationships were moderated by years
      in the United States. Data are from adults participating in an Asian American
      supplement to the 2001 Health Care Quality Survey. Language and racial
      discrimination in seeking health care were independently associated with
      increased number of chronic health conditions after controlling for age, sex,
      education, family income, health insurance, primary language, nativity, and
      ethnicity. Language discrimination was significantly associated with health
      conditions even with the presence of racial discrimination in the statistical
      model. Racial discrimination did not show a significant association in the full
      analytic model. The relationship between language discrimination and chronic
      conditions was stronger for Asian immigrants living in the USA 10 years or more
      compared to more recently arrived immigrants. Language discrimination may be an
      understudied type of discrimination associated with chronic illness among Asian
      Americans.

PMID- 19095343
TI  - Short-term effects of two continuous combined oestrogen-progestogen therapies on
      several cardiovascular risk markers in healthy postmenopausal women: a randomised
      controlled trial.
AB  - OBJECTIVE: To compare the short-term effects of two oral continuous combined
      oestrogen-progestogen treatment regimens on blood concentrations of several
      cardiovascular risk markers in healthy postmenopausal women. STUDY DESIGN: In a
      12-week randomised controlled study, 48 healthy non-hysterectomised
      postmenopausal women, aged 41-58 years, received either no treatment (control
      group; n=16), or daily oral continuous combined treatment with 1 mg micronised
      17beta-oestradiol plus 5 mg dydrogesterone (E/D group; n=18) or 0.625 mg
      conjugated equine oestrogens plus 5 mg medroxyprogesterone acetate (CEE/MPA
      group; n=14). Fasting blood sampling was performed at baseline and after 12 weeks
      of follow-up. RESULTS: Compared with the control group, 12-week treatment with
      E/D or CEE/MPA reduced fibrinogen (-7.7%, p=0.004 and -3.3%, p=0.083,
      respectively), factor VII-act (-8.7%, p=0.14 and -9.7%, p=0.06, respectively),
      homocysteine (-20.5%, p=0.02 and -26.7%, p=0.005, respectively), and IGF-1 (
      27.9%, p<0.001 and -18.1%, p=0.002, respectively), but increased factor VII-ag
      (+10.1%, p=0.03 and +4.4%, p=0.46, respectively), endothelin-1 (+15.2%, p=0.12
      and +20.0%, p=0.13, respectively) and C-reactive protein (+88.8%, p=0.18 and
      +71.0%, p=0.44, respectively). Fibrinolytic factors were not affected by either
      hormone therapy (HT). CONCLUSIONS: Short-term oral continuous combined therapy
      with oestradiol/dydrogesterone and conjugated equine
      oestrogens/medroxyprogesterone acetate had comparable effects on the investigated
      cardiovascular risk markers.

PMID- 19095344
TI  - Oestrogens and prostate cancer: novel concepts about an old issue.

PMID- 19095345
TI  - A study of diffusion-weighted magnetic resonance imaging in men with untreated
      localised prostate cancer on active surveillance.
AB  - BACKGROUND: Markers that predict the behaviour of localised prostate cancer are
      needed to identify patients that require treatment. OBJECTIVE: We have analysed
      the apparent diffusion coefficient (ADC) generated from diffusion-weighted
      magnetic resonance imaging (DW-MRI) with respect to repeat biopsy findings and
      time to radical treatment in patients in a prospective study of active
      surveillance. DESIGN, SETTING, AND PARTICIPANTS: Some 86 men recruited between
      2002 and 2006 were followed for a median of 29 mo. Patients had clinical stage
      T1/T2a N0/Nx M0/Mx adenocarcinoma of the prostate, prostate-specific antigen
      (PSA) level<15 ng/ml, Gleason score<=7, primary Gleason grade<=3, and positive
      biopsy cores (pbc)<=50%. MEASUREMENTS: All patients had DW-MRI in addition to
      standard MRI sequences. Tumour regions of interest (ROIs) were identified using
      T2-weighted fast-spin echo images as focal areas of restricted diffusion.
      Univariate analyses including all clinical variables and tumour ADC data were
      performed with respect to repeat biopsy findings and time to radical treatment.
      Receiver operating curves (ROC) compared predictive variables. RESULTS AND
      LIMITATIONS: Patients in the study had a median age of 66 yr and a median initial
      PSA level of 6.7 ng/ml. Some 39 patients (45%) received deferred radical
      treatment, and 34 patients (40%) had adverse histology on repeat biopsy.
      According to univariate analysis, tumour ADC was a significant predictor of both
      adverse repeat biopsy findings (p<0.0001; hazard ratio [HR]: 1.3; 95% confidence
      interval [CI]: 1.1-1.6), and time to radical treatment (p<0.0001; HR: 1.5; 95%
      CI: 1.2-1.8). ROC curves for ADC showed an area under the curve (AUC) of 0.7 for
      prediction of adverse repeat biopsy findings and an AUC of 0.83 for prediction of
      radical treatment. CONCLUSIONS: In patients with low-risk, localised disease,
      tumour ADC on DW-MRI may be a useful marker of prostate cancer progression and
      may help to identify patients who stand to benefit from radical treatment. This
      possibility warrants further study.

PMID- 19095346
TI  - Editorial comment on: A study of diffusion-weighted magnetic resonance imaging in
      men with untreated localized prostate cancer on active surveillance.

PMID- 19095347
TI  - Japanese encephalitis in Western Europe.
AB  - Japanese encephalitis is the leading cause of viral encephalitis in Asia. In
      Western Europe, however, Japanese encephalitis has not been reported so far. We
      report on a 59-year-old German woman with typical neurological symptoms and
      clinical presentation 8 days after a journey to northern China. The case report
      summarizes the patient's clinical course as well as pathological findings in
      blood samples, the cerebro-spinal fluid, MRI scans, and EEGs.

PMID- 19095349
TI  - Marchantin C, a novel microtubule inhibitor from liverwort with anti-tumor
      activity both in vivo and in vitro.
AB  - Microtubules are long-standing targets in cancer chemotherapy. Previously, we
      reported that marchantin C triggers apoptosis of human tumor cells. We show here
      that marchantin C induced cell cycle arrest at G(2)/M phase in A172 and HeLa
      cells. In addition, marchantin C decreased the quantity of microtubules in a time
      and dose-dependent manner in these cells. Exposure of purified bovine brain
      tubulin to marchantin C inhibited polymerization of gross tubulin in vitro.
      Moreover, marchantin C potently suppressed the growth of human cervical carcinoma
      xenografts in nude mice. Marchantin C-treated xenografts showed decreased
      microtubules, Bcl-2 and increased cyclin B1, Bax, caspase-3, indicating that
      marchantin C possess the same ability to induce microtubules depolymerization and
      tumor cell apoptosis in tumor-bearing mice as in vitro. In conclusion, marchantin
      C is a novel microtubule inhibitor that induces mitotic arrest of tumor cells and
      suppresses tumor cell growth, exhibiting promising antitumor therapeutic
      potential.

PMID- 19095350
TI  - Human hepatocellular carcinoma: expression profiles-based molecular
      interpretations and clinical applications.
AB  - Primary liver cancer is the fifth most common cancer worldwide and hepatocellular
      carcinoma (HCC) accounts for over 85% of all primary liver cancers. The clinical
      management of advanced and metastatic HCC is challenging on many counts. Besides
      largely occurs within a background of underlying chronic liver disease and
      cirrhosis, HCC is a phenotypically and genetically heterogeneous polyclonal
      disease and resistant to most conventional chemotherapy. Early manifestation of
      HCC is characteristically slow growing with few symptoms, and HCC is therefore
      often diagnosed at an advanced stage when potentially curative surgical or local
      ablative therapy is not feasible. In this review, I have summarized my
      presentation at the recent HCC workshop at IARC, Lyon, on our knowledge generated
      from comprehensive molecular studies of primary liver cancer tissues and attempt
      to translate these results to gain molecular insights, especially on
      identification of biomarkers that could confer pathological and functional
      changes associated with the pathogenesis and progression of HCC, hoping to
      provide important molecular basis for the development of novel diagnosis and
      treatments to alter clinical outcomes of this disease.

PMID- 19095348
TI  - Stem cells in melanoma development.
AB  - Cutaneous melanoma is a significant health problem worldwide. Available
      treatments can induce objective tumor regression in a small percent of patients,
      but these responses are not always associated with improved long-term survival.
      The resistance of melanoma to therapy and its predestined recurrence are related
      to the genetic heterogeneity and genomic instability of the tumor. For many years
      these genetic alterations were thought to be linked to the accumulation of random
      mutations in functionally differentiated cells which transform them into
      malignant cells that have lost their ability to differentiate and have acquired
      drug resistance. In the last few years it has been largely demonstrated that
      melanoma as other solid tumors contains a subpopulation of cells (CSCs)
      considered the source of the primary tumor mass, of new tumor nodules and
      responsible for drug resistance and cancer recurrence. In this review, we provide
      an overview of findings and advances in CSCs research that are relevant to the
      initiation, natural history, and the response to treatment of malignant melanoma.

PMID- 19095351
TI  - Simultaneous sorption of crystal violet and 2-naphthol to bentonite with
      different CECs.
AB  - This work was to examine the feasibility and efficiency to use bentonite for
      simultaneous removal of cationic dyes and hydrophobic organic carbons (HOCs) from
      water. The sorption capacities of crystal violet (CV) on two bentonites and one
      activated carbon were compared. Simultaneous sorption of CV and 2-naphthol on the
      two bentonites were tested, and the removal efficiencies of 2-naphthol by the
      simultaneous sorption method and by CV modified bentonite was also compared. The
      experimental results in this study showed that the bentonite is more effective in
      sorption of CV than the activated carbon. With the sorption of CV, bentonite
      surfaces were altered from hydrophilicity to hydrophobicity, and thus 2-naphthol
      could be simultaneously removed. The aromatic effect between CV and 2-naphthol
      was supposed to be the primary driving force for the sorption of 2-naphthol. The
      simultaneous sorption method was shown to be more effective in the sorption of 2
      naphthol than the CV modified bentonite. Results of this work could provide novel
      information for the treatment of wastewater containing both cationic dyes and
      HOCs.

PMID- 19095352
TI  - Quantifying effects of pH and surface loading on arsenic adsorption on NanoActive
      alumina using a speciation-based model.
AB  - Arsenic (As) poses a significant water quality problem and challenge for the
      environmental engineers and scientists throughout the world. Batch tests were
      carried out in this study to investigate the adsorption of As(V) on NanoActive
      alumina. The arsenate adsorption envelopes on NanoActive alumina exhibited broad
      adsorption maxima when the initial As(V) loading was less than a 50 mg g(-1)
      sorbent. As the initial As(V) loading increased to 50 mg g(-1) sorbent, a
      distinct adsorption maximum was observed at pH 3.2-4.6. FTIR spectra revealed
      that only monodentate complexes were formed upon the adsorption of arsenate on
      NanoActive alumina over the entire pH range and arsenic loading conditions
      examined in this study. A speciation-based adsorption model was developed to
      describe arsenate adsorption on NanoActive alumina and it could simulate arsenate
      adsorption very well in a broad pH range of 1-10, and a wide arsenic loading
      range of 0.5-50 mg g(-1) adsorbent. Only four adjustable parameters, including
      three adsorption constants, were included in this model. This model offers a
      substantial improvement over existing models in accuracy and simplification in
      quantifying pH and surface loading effects on arsenic adsorption.

PMID- 19095353
TI  - Adsorption of trichloroethylene and benzene vapors onto hypercrosslinked
      polymeric resin.
AB  - In this research, the adsorption equilibria of trichloroethylene (TCE) and
      benzene vapors onto hypercrosslinked polymeric resin (NDA201) were investigated
      by the column adsorption method in the temperature range from 303 to 333 K and
      pressures up to 8 kPa for TCE, 12 kPa for benzene. The Toth and Dubinin-Astakov
      (D-A) equations were tested to correlate experimental isotherms, and the
      experimental data were found to fit well by them. The good fits and
      characteristic curves of D-A equation provided evidence that a pore-filling
      phenomenon was involved during the adsorption of TCE and benzene onto NDA-201.
      Moreover, thermodynamic properties such as the Henry's constant and the isosteric
      enthalpy of adsorption were calculated. The isosteric enthalpy curves varied with
      the surface loading for each adsorbate, indicating that the hypercrosslinked
      polymeric resin has an energetically heterogeneous surface. In addition, a simple
      mathematic model developed by Yoon and Nelson was applied to investigate the
      breakthrough behavior on a hypercrosslinked polymeric resin column at 303 K and
      the calculated breakthrough curves were in high agreement with corresponding
      experimental data.

PMID- 19095354
TI  - Cold-induced aggregation microextraction based on ionic liquids and fiber optic
      linear array detection spectrophotometry of cobalt in water samples.
AB  - A new simple and rapid cold-induced aggregation microextraction (CIAME) method
      was applied to preconcentrate cobalt(II) ions from water samples as a prior step
      to its determination by fiber optic-linear array detection spectrophotometry (FO
      LADS). In this method, very small amounts of 1-hexyl-3-methylimidazolium
      hexafluorophosphate [Hmim][PF(6)] and 1-hexyl-3-methylimidazolium bis
      (trifluoromethylsulfonyl) imide [Hmim][Tf(2)N] as hydrophobic ionic liquids (ILs)
      and extractant solvents were dissolved in the sample solution containing Triton X
      114 (anti-sticking agent). 1-(2-Pyridylazo)-2-naphthol (PAN) was chosen as the
      complexing agent. After dissolving, the solution was cooled in the ice bath and a
      cloudy solution was formed of IL fine droplets due to the decrease of IL
      solubility. After centrifuging, the fine droplets of extractant phase were
      settled to the bottom of the conical-bottom centrifuge tube. Analysis was carried
      out by a fiber optic-linear array detector spectrophotometer at 570 nm. In this
      method, which is robust against high content of salt and water-miscible organic
      solvents, various parameters were investigated and optimized. The applicability
      of the technique was evaluated by the determination of trace amounts of cobalt in
      several water samples. Under the optimum conditions, the limit of detection (LOD)
      of the method was 0.14 ng mL(-1) and the relative standard deviation (R.S.D.) for
      30 ng mL(-1) cobalt was 2.32%.

PMID- 19095355
TI  - Removal of BTEX vapours from waste gas streams using silica aerogels of different
      hydrophobicity.
AB  - Silica aerogels are alternative adsorbents to activated carbon (AC) for the
      removal and the recovery of organic vapours from gas streams. The adsorption
      capacity measurements of different silica aerogels were done by mini-column
      method. Continuous adsorption measurements show that silica aerogels are
      excellent adsorbents of BTEX vapours from waste gas stream. Compared to the most
      used adsorbents, such as AC and silica gel, aerogels exhibit capacities which
      enormously exceed that of both commonly used adsorbents. By increasing the degree
      of hydrophobicity, aerogels become less effective, but they do not adsorb water
      vapour from gas stream. Silica monolith aerogels with different degrees of
      hydrophobicity by incorporating methyltrimethoxysilane (MTMS) or
      trimethylethoxysilane (TMES) in standard sol-gel synthesis were prepared.
      Excellent properties of aerogels, obtained with the sol-gel synthesis, were
      preserved with supercritical drying with CO(2). The degree of hydrophobicity of
      the aerogels was tested by measuring the contact angle (theta) of a water droplet
      with the aerogel surface. The aerogels were also characterised by FTIR, nitrogen
      sorption and DSC/TG measurements.

PMID- 19095356
TI  - Do burn injuries during infancy affect pain and sensory sensitivity in later
      childhood?
AB  - Studies in animals and humans suggest that neonatal and early infant pain or
      stress experiences can induce long-term alterations in somatosensory and pain
      processing. We studied pain and sensory sensitivity in school-aged children (9-16
      years) who had suffered moderate (N=24) or severe (N=24) burn injuries in infancy
      (6-24 months of age) and 24 controls. Quantitative sensory testing entailing
      detection and pain thresholds for thermal and mechanical stimuli and perceptual
      sensitization to tonic heat and repetitive mechanical stimuli was performed. Two
      testing sites (thenar, trigeminal region), both not affected by the burn injury,
      were used to determine whether there are global changes in pain sensitivity. The
      result pattern suggests a differential impact of burn severity. Compared to
      controls, moderately burned children showed significantly higher mechanical
      detection thresholds (thenar) and significantly lower mechanical pain thresholds
      and significantly greater perceptual sensitization to repetitive mechanical
      stimuli (both testing sites). No significant alterations were observed for
      thermal stimuli. In contrast, severely burned children showed, compared to
      controls, primarily alterations in thermal pain sensitivity (elevated pain
      thresholds at both testing sites, significantly greater perceptual sensitization
      at the thenar). In these children, mechanical pain sensitivity and detection
      thresholds were not consistently altered. This differential pattern of altered
      sensory and pain sensitivity may reflect differences in experienced stress, pain
      and analgesic treatment between moderately and severely burned children. Most
      importantly, our findings suggest that early traumatic and painful injuries, such
      as burns, can induce global, long-term alterations in sensory and pain
      processing.

PMID- 19095357
TI  - Motoneurone recruitment is altered with pain induced in non-muscular tissue.
AB  - Motoneurone discharge rate is reduced despite the maintenance of force when pain
      is induced via injection of hypertonic saline into muscle. Two aspects require
      consideration. First, hypertonic saline may have direct effects on axons other
      than small diameter pain fibres including the motoneurones that innervate the
      painful muscle. Second, it is unclear how force is maintained, when motoneurone
      discharge rate is decreased. We aimed to determine; (1) if motoneurone discharge
      rate is reduced during force-matched tasks when pain is induced in non-muscle
      tissue (to exclude direct effects on motoneurones) and (2) if the reduction of
      discharge rate is associated with additional changes in motoneurone recruitment
      over multiple muscle regions. Motoneurone discharge was recorded in the
      quadriceps with eight pairs of fine-wire electrodes. Seven subjects performed 30
      s low-level, force-matched contractions before and during anterior knee pain,
      which was induced by a bolus (0.25ml) injection of 5% hypertonic saline into the
      infra-patellar fat pad. In total, 119 motor units were identified. Of these, 34
      were identified both before and during pain. The discharge rate of these units
      decreased during pain from 8.9(1.5) to 7.2(1.4)Hz (P<0.0001). In addition, 31
      units were recruited in the no-pain condition but not during pain, when 53 new
      units were recruited. These changes coincided with a large variability in gross
      muscle activity measures between muscle regions. These data confirm that
      motoneurone recruitment is altered when direct effects of saline on motoneurones
      are excluded. Recruitment of additional motor units may explain force maintenance
      despite reduced discharge rate of some units.

PMID- 19095358
TI  - Salivary cortisol as a biomarker in stress research.
AB  - Salivary cortisol is frequently used as a biomarker of psychological stress.
      However, psychobiological mechanisms, which trigger the hypothalamus-pituitary
      adrenal axis (HPAA) can only indirectly be assessed by salivary cortisol
      measures. The different instances that control HPAA reactivity (hippocampus,
      hypothalamus, pituitary, adrenals) and their respective modulators, receptors, or
      binding proteins, may all affect salivary cortisol measures. Thus, a linear
      relationship with measures of plasma ACTH and cortisol in blood or urine does not
      necessarily exist. This is particularly true under response conditions. The
      present paper addresses several psychological and biological variables, which may
      account for such dissociations, and aims to help researchers to rate the validity
      and psychobiological significance of salivary cortisol as an HPAA biomarker of
      stress in their experiments.

PMID- 19095359
TI  - Athletic identity, descriptive norms, and drinking among athletes transitioning
      to college.
AB  - College student-athletes are at risk for heavy alcohol consumption and related
      consequences. The present study evaluated the influence of college student and
      college athlete descriptive norms and levels of athletic identity on drinking and
      related consequences among incoming college students attending two universities
      (N=1119). Prior to the beginning of their first year of college, students
      indicating high school athletic participation completed assessments of athletic
      identity, alcohol consumption, drinking-related consequences, and normative
      perceptions of alcohol use. Estimations of drinking by college students and
      student-athletes were significantly greater than self-reported drinking. Athletic
      identity moderated associations among gender, perceived norms, drinking, and
      related consequences. Athlete-specific norms had a stronger effect on drinking
      among those reporting higher levels of athletic identity, and higher levels of
      athletic identity exclusively protected males from experiencing drinking-related
      consequences. Implications of the role of athletic identity in the development of
      social norms interventions targeted at high school athletes transitioning to
      college are discussed.

PMID- 19095360
TI  - Relationship between smoking status and body weight in a military population of
      young adults.
AB  - The purpose of the present study was to determine the association between smoking
      and body weight in a cohort of young U.S. Air Force recruits (mean age=20 years)
      enrolled in basic military training (N=35986). Twenty-two percent of recruits
      smoked daily prior to basic military training (n=8087) and were compared to never
      smokers, former smokers, and experimental or nondaily smokers. A three-way
      interaction among smoking status, gender and ethnicity suggested a small effect
      for daily smoking among White male recruits only and no significant differences
      for female recruits or members of any other ethnic group. Although there was a
      statistically significant relationship between smoking and body weight in White
      males, the effect size was approximately 1 kg. These results suggest that the
      energy balance differences in body weight between young smokers and nonsmokers
      are minimal and that it would take decades to accrue the differences typically
      seen in adult smokers.

PMID- 19095361
TI  - Using the Prototype/Willingness model to predict smoking behaviour among
      Norwegian adolescents.
AB  - This paper examines cognitive antecedents of non-smoking among adolescents who
      reported smoking less than 1-2 times a week, and reported non-smoking intentions
      and willingness, in the framework of the Prototype/Willingness model. Two waves
      of data were obtained from a nation-wide sample of 760 Norwegian adolescents who
      responded to a school-based survey on smoking. Structural equation modelling was
      used to evaluate the predictive power of the social reaction pathway (prototype
      and willingness) of the P/W model, and in addition, the constructs from the
      Theory of Reasoned Action (subjective norm, attitude and intention). Results
      demonstrated the unique importance of the social reaction path when examining
      smoking behaviour among non-smoking adolescents. Implications of the findings and
      possible applications are discussed.

PMID- 19095362
TI  - Does cervical vertebrae length correlate with cervical spondylotic myelopathy?

PMID- 19095363
TI  - Incense - A problematic method of drug-delivery.

PMID- 19095364
TI  - Cardiovascular disease may lead to female sexual dysfunction.

PMID- 19095365
TI  - Chronic prostatitis/chronic pelvic pain syndrome in males may be an autoimmune
      disease, potentially responsive to corticosteroid therapy.
AB  - Chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) represents the most
      common form of prostatitis. No known etiology factor in most cases can be found.
      It is possible that at least in some cases autoimmune response could be causative
      factor. Common treatment options include antibiotics, alpha blockers,
      myorelaxants, phytotherapeuticals, non steroidal anti-inflammatory drugs,
      hormonal treatment and surgery but corticosteroids have not been investigated.
      HYPOTHESIS: Chronic pelvic pain syndrome is in some cases autoimmune disease and
      this could have repercussions on treatment using low dose corticosteroids.
      RATIONALE: Currently corticosteroids are not a standard treatment option in
      CP/CPPS. Theoretical, experimental and scarce clinical evidence suggest that
      treatment with low dose corticosteroids could be beneficial in some patients with
      chronic prostatitis. If our hypothesis could be supported with well designed,
      randomized clinical trials this could change the approach of the medical
      treatment of CP/CPPS.

PMID- 19095366
TI  - Does angiotensin II-aldosterone have a role in radiation-induced heart disease?
AB  - Radiation-induced heart disease (RIHD) is the potentially lethal side effect of
      radiation therapy. Clinical trials and epidemiologic studies show the adverse
      impact of RIHD on the outcome of long-term cancer survivors. However, what
      factors affect RIHD and how RIHD develop are not yet clear. On the other hand, as
      we all known, angiotensin II (Ang II) and aldosterone play a vital
      pathophysiological role in the common cardiovascular disease, including
      hypertension, atherosclerosis, heart failure, myocardial infarction and cardiac
      hypertrophy. The pathophysiology of these various syndromes is similar, starting
      by prior microvascular injury that leads to subsequent myocardium ischemia, all
      of which cause late fibrous scars. So the pathophysiology of RIHD is similar to
      the common heart diseases induced by angiotensin-aldosterone. But the effect of
      angiotensin-aldosterone on RIHD has little been studied. Thus, in the present
      hypothesis we suggest that angiotensin II-aldosterone plays an important
      pathophysical role in RIHD, which was confirmed by our pilot study.

PMID- 19095367
TI  - Development and external validation of prognostic model for 2-year survival of
      non-small-cell lung cancer patients treated with chemoradiotherapy.
AB  - PURPOSE: Radiotherapy, combined with chemotherapy, is the treatment of choice for
      a large group of non-small-cell lung cancer (NSCLC) patients. Recent developments
      in the treatment of these patients have led to improved survival. However, the
      clinical TNM stage is highly inaccurate for the prediction of survival, and
      alternatives are lacking. The objective of this study was to develop and validate
      a prediction model for survival of NSCLC patients, treated with
      chemoradiotherapy. PATIENTS AND METHODS: The clinical data from 377 consecutive
      inoperable NSCLC patients, Stage I-IIIB, treated radically with chemoradiotherapy
      were collected. A prognostic model for 2-year survival was developed, using 2
      norm support vector machines. The performance of the model was expressed as the
      area under the curve of the receiver operating characteristic and assessed using
      leave-one-out cross-validation, as well as two external data sets. RESULTS: The
      final multivariate model consisted of gender, World Health Organization
      performance status, forced expiratory volume in 1 s, number of positive lymph
      node stations, and gross tumor volume. The area under the curve, assessed by
      leave-one-out cross-validation, was 0.74, and application of the model to the
      external data sets yielded an area under the curve of 0.75 and 0.76. A high- and
      low-risk group could be clearly identified using a risk score based on the model.
      CONCLUSION: The multivariate model performed very well and was able to accurately
      predict the 2-year survival of NSCLC patients treated with chemoradiotherapy. The
      model could support clinicians in the treatment decision-making process.

PMID- 19095368
TI  - Cone-beam computed tomographic image guidance for lung cancer radiation therapy.
AB  - PURPOSE: To determine the geometric accuracy of lung cancer radiotherapy using
      daily volumetric, cone-beam CT (CBCT) image guidance and online couch position
      adjustment. METHODS AND MATERIALS: Initial setup accuracy using localization CBCT
      was analyzed in three lung cancer patient cohorts. The first (n = 19) involved
      patients with early-stage non-small-cell lung cancer (NSCLC) treated using
      stereotactic body radiotherapy (SBRT). The second (n = 48) and third groups (n =
      20) involved patients with locally advanced NSCLC adjusted with manual and remote
      controlled couch adjustment, respectively. For each group, the couch position was
      adjusted when positional discrepancies exceeded +/-3 mm in any direction, with
      the remote-controlled couch correcting all three directions simultaneously.
      Adjustment accuracy was verified with a second CBCT. Population-based setup
      margins were derived from systematic (Sigma) and random (sigma) positional errors
      for each group. RESULTS: Localization imaging demonstrates that 3D positioning
      errors exceeding 5 mm occur in 54.5% of all delivered fractions. CBCT reduces
      these errors; post-correction Sigma and sigma ranged from 1.2 to 1.9 mm for Group
      1, with 82% of all fractions within +/-3 mm. For Group 2, Sigma and sigma ranged
      between 0.8 and 1.8 mm, with 76% of all treatment fractions within +/-3 mm. For
      Group 3, the remote-controlled couch raised this to 84%, and Sigma and sigma were
      reduced to 0.4 to 1.7 mm. For each group, the postcorrection setup margins were 4
      to 6 mm, 3 to 4 mm, and 2 to 3 mm, respectively. CONCLUSIONS: Using IGRT, high
      geometric accuracy is achievable for NSCLC patients, potentially leading to
      reduced PTV margins, improved outcomes and empowering adaptive radiation therapy
      for lung cancer.

PMID- 19095369
TI  - Pelvic lymph node topography for radiotherapy treatment planning from ferumoxtran
      10 contrast-enhanced magnetic resonance imaging.
AB  - PURPOSE: To define a population-based pelvic lymph node clinical target volume
      (CTV) for radiotherapy treatment planning using magnetic resonance (MR) imaging
      and the ultrasmall superparamagnetic iron oxide lymph node contrast agent
      ferumoxtran-10. METHODS AND MATERIALS: A total of 55 eligible patients with
      endometrial, cervical, prostate, or bladder cancer underwent MR imaging sessions
      before and after contrast administration on 2 consecutive days. Ferumoxtran-10
      was administered immediately after the first scan. The three-dimensional spatial
      distribution of the pelvic lymph nodes was determined in relation to adjacent
      vessels and other musculoskeletal landmarks, from which guidelines for
      determining a nodal CTV in individual patients were developed. RESULTS: On
      average, 30 lymph nodes (range, five to 62 nodes) were identified in each
      patient. The distribution of nodal distances to the closest artery or vein was
      observed to vary in different anatomic regions. Symmetrical three-dimensional
      margins of expansion around the distal para-aortic (12 mm), common iliac (10 mm),
      external iliac (9 mm), and internal iliac (10 mm) vessels, drawn in continuity
      with a 12-mm expansion anterior to the sacrum and a 22-mm expansion medial to the
      pelvic sidewall, were shown to encompass the majority of detectable lymph nodes
      in most patients. CONCLUSION: Use of MR lymphography with ferumoxtran-10 provides
      an objective description of lymph node locations for radiotherapy planning. Use
      of this nodal CTV model in clinical practice could ensure a high probability of
      encompassing the regions at risk of harboring metastatic disease while minimizing
      the dose to adjacent normal tissues.

PMID- 19095370
TI  - Motion analysis of 100 mediastinal lymph nodes: potential pitfalls in treatment
      planning and adaptive strategies.
AB  - PURPOSE: The motion of mediastinal lymph nodes may undermine local control with
      involved-field radiotherapy. We studied patterns of nodal and tumor motion in 41
      patients with lung cancer. METHODS AND MATERIALS: Four-dimensional (4D) computed
      tomography planning scans were retrospectively evaluated to identify patients
      with clearly visible mediastinal lymph nodes. One hundred nodes from 14 patients
      with Stage I and 27 patients with Stage III were manually contoured in all 4D
      computed tomography respiratory phases. Motion was derived from changes in the
      nodal center-of-mass position. Primary tumors were also delineated in all phases
      for 16 patients with Stage III disease. Statistical analysis included a
      multivariate mixed-effects model of grouped data. RESULTS: Average 3D nodal
      motion during quiet breathing was 0.68 cm (range, 0.17-1.64 cm); 77% moved
      greater than 0.5 cm, and 10% moved greater than 1.0 cm. Motion was greatest in
      the lower mediastinum (p = 0.002), and nodes measuring 2 cm or greater in
      diameter showed motion similar to that in smaller nodes. In 11 of 16 patients
      studied, at least one node moved more than the corresponding primary tumor. No
      association between 3D primary tumor motion and nodal motion was observed. For
      mobile primary tumors, phase offsets between the primary tumor and nodes of two
      or more and three or more phases were observed for 33% and 12% of nodes,
      respectively. CONCLUSIONS: Mediastinal nodal motion is common, with phase offsets
      seen between the primary tumor and different nodes in the same patient. Patient
      specific information is needed to ensure geometric coverage, and adaptive
      strategies based solely on the primary tumor may be misleading.

PMID- 19095371
TI  - Alterations in hormone levels after adjuvant chemoradiation in male rectal cancer
      patients.
AB  - PURPOSE: To evaluate follicle-stimulating hormone (FSH), luteinizing hormone
      (LH), and testosterone levels after postoperative chemoradiation in men with
      rectal cancer. METHODS AND MATERIALS: Forty-three men with rectal cancer had
      baseline and postchemoradiation FSH, LH, and testosterone measured. Adjuvant
      chemoradiation consisted of two 5-day cycles of bolus 5-fluorouracil (5-FU) every
      4 weeks at a dose of 500 mg/m(2)/d followed by concurrent chemoradiation followed
      by two additional 5-day cycles of 5-FU at a dose of 450 mg/m(2)/d. Continuous
      infusion 5-FU at 225 mg/m(2)/d was given during radiation. Pelvic radiation
      consisted of a three- or four-field technique with a median dose of 54.0 Gy in 30
      fractions. RESULTS: Median follow-up was 6.1 years. Mean baseline FSH levels
      increased from 5.3 to a peak of 23.9 IU/L (p < 0.001) 13-24 months after
      chemoradiation. Mean baseline LH levels increased from 4.3 to a peak of 8.5 IU/L
      (p < 0.001) within 6 months after chemoradiation. Mean testosterone levels
      decreased from 15.4 nmol/L at baseline to 8.0 nmol/L more than 4 years after
      chemoradiation. Mean testosterone to mean LH ratio decreased from 4.4 at baseline
      to 1.1 after 48 months posttreatment, suggesting a continued decrease in Leydig
      cell function with time. Testicular dose was measured in 5 patients. Median dose
      was 4 Gy (range, 1.5-8.9 Gy). CONCLUSIONS: Chemoradiation in men with rectal
      cancer causes persistent increases in FSH and LH levels and decreases in
      testosterone levels.

PMID- 19095372
TI  - Phase II study of high-dose photon/proton radiotherapy in the management of spine
      sarcomas.
AB  - PURPOSE: Radiotherapy (XRT) for spine sarcomas is constrained by spinal cord,
      nerve, and viscera tolerance. Negative surgical margins are uncommon; hence,
      doses of >or=66 Gy are recommended. A Phase II clinical trial evaluated high-dose
      photon/proton XRT for spine sarcomas. METHODS AND MATERIALS: Eligible patients
      had nonmetastatic, thoracic, lumbar, and/or sacral spine/paraspinal sarcomas.
      Treatment included pre- and/or postoperative photon/proton XRT with or without
      radical resection; patients with osteosarcoma and Ewing's sarcoma received
      chemotherapy. Shrinking fields delivered 50.4 cobalt Gray equivalent (Gy RBE) to
      subclinical disease, 70.2 Gy RBE to microscopic disease in the tumor bed, and
      77.4 Gy RBE to gross disease at 1.8 Gy RBE qd. Doses were reduced for
      radiosensitive histologies, concurrent chemoradiation, or when diabetes or
      autoimmune disease present. Spinal cord dose was limited to 63/54 Gy RBE to
      surface/center. Intraoperative boost doses of 7.5 to 10 Gy could be given by
      dural plaque. RESULTS: A total of 50 patients (29 chordoma, 14 chondrosarcoma, 7
      other) underwent gross total (n = 25) or subtotal (n = 12) resection or biopsy (n
      = 13). With 48 month median follow-up, 5-year actuarial local control, recurrence
      free survival, and overall survival are: 78%, 63%, and 87% respectively. Two of
      36 (5.6%) patients treated for primary versus 7/14 (50%) for recurrent tumor
      developed local recurrence (p < 0.001). Five patients developed late radiation
      associated complications; no myelopathy developed but three sacral neuropathies
      appeared after 77.12 to 77.4 Gy RBE. CONCLUSIONS: Local control with this
      treatment is high in patients radiated at the time of primary presentation.
      Spinal cord dose constraints appear to be safe. Sacral nerves receiving 77.12
      77.4 Gy RBE are at risk for late toxicity.

PMID- 19095373
TI  - Target definition by C11-methionine-PET for the radiotherapy of brain metastases.
AB  - PURPOSE: To evaluate the ability of 11C-methionine positron emission tomography
      (MET-PET) to delineate target volumes for brain metastases and to investigate to
      what extent tumor growth is presented by magnetic resonance imaging (MRI) and MET
      PET. MATERIALS AND METHODS: Three observers undertook target definition in 19
      patients with 95 brain metastases by MRI and MET-PET images. MRI gross target
      volume (GTV) (GTV-MRI) was defined as the contrast-enhanced area on gadolinium
      enhanced T1-weighted MRI. MET-PET GTV (GTV-PET) was defined as the area of an
      accumulation of MET-PET apparently higher than that of normal tissue on MET-PET
      images. The size of occupation ratio was determined using the following equation:
      SOR (%) of MET are within x mm margin outside GTV-MRI = the volume of the GTV-PET
      within x mm outside the GTV-MRI/the volume of the GTV-PET. RESULTS: For GTV-MRI
      volumes of <or=0.5 mL, the sensitivity of tumor detection by MET-PET was 43%. For
      GTV-MRI volume of >0.5 mL, GTV-PET volumes were larger than GTV-MRI volumes and a
      significant correlation was found between these variables by linear regression.
      For all tumor sizes and tumor characteristics, a 2-mm margin outside the GTV-MRI
      significantly improved the coverage of the GTV-PET. CONCLUSIONS: Although there
      were some limitations in our study associated with spatial resolution, blurring
      effect, and image registrations with PET images, MET-PET was supposed to have a
      potential as a promising tool for the precise delineation of target volumes in
      radiotherapy planning for brain metastases.

PMID- 19095374
TI  - Stereotactic body radiotherapy is effective salvage therapy for patients with
      prior radiation of spinal metastases.
AB  - PURPOSE: To provide actuarial outcomes and dosimetric data for spinal/paraspinal
      metastases, with and without prior radiation, treated with stereotactic body
      radiotherapy (SBRT). METHODS AND MATERIALS: A total of 39 consecutive patients
      (60 metastases) were treated with SBRT between April 2003 and August 2006 and
      retrospectively reviewed. In all, 23 of 60 tumors had no previous radiation
      (unirradiated) and 37/60 tumors had previous irradiation (reirradiated). Of 37
      reirradiated tumors, 31 were treated for "salvage" given image-based tumor
      progression. Local failure was defined as progression by imaging and/or
      clinically. RESULTS: At last follow-up, 19 patients were deceased. Median patient
      survival time measured was 21 months (95% CI = 8-27 months), and the 2-year
      survival probability was 45%. The median total dose prescribed was 24 Gy in three
      fractions prescribed to the 67% and 60% isodose for the unirradiated and
      reirradiated cohorts, respectively. The median tumor follow-up for the
      unirradiated and reirradiated group was 9 months (range, 1-26) and 7 months
      (range, 1-48) respectively. Eight of 60 tumors have progressed, and the 1- and 2
      year progression-free probability (PFP) was 85% and 69%, respectively. For the
      salvage group the 1 year PFP was 96%. There was no significant difference in
      overall survival or PFP between the salvage reirradiated vs. all other tumors
      treated (p = 0.08 and p = 0.31, respectively). In six of eight failures the
      minimum distance from the tumor to the thecal sac was <or=1 mm. Of 60 tumors
      treated, 39 have >or=6 months follow-up and no radiation-induced myelopathy or
      radiculopathy has occurred. CONCLUSION: Spine SBRT has shown preliminary efficacy
      and safety in patients with image-based progression of previously irradiated
      metastases.

PMID- 19095375
TI  - Evaluation of different score index for predicting prognosis in gamma knife
      radiosurgical treatment for brain metastasis.
AB  - PURPOSE: To assess the utility of the Radiation Therapy Oncology Group Recursive
      Partitioning Analysis (RPA) and Score Index for Radiosurgery (SIR) stratification
      systems in predicting survival in patients with brain metastasis treated with
      Gamma Knife radiosurgery (GKRS). METHODS AND MATERIALS: A total of 185 patients
      were included in the study. Patients were stratified according to RPA and SIR
      classes. The RPA and SIR classes, age, Karnofsky Performance Status (KPS), and
      systemic disease were correlated with survival. RESULTS: Five patients were lost
      to follow-up. Median survival in patients in RPA Class 1 (30 patients) was 17
      months; in Class 2 (140 patients), 10 months; and in Class 3 (10 patients), 3
      months. Median survival in patients in SIR Class 1 (30 patients) was 3 months; in
      Class 2 (135 patients), 8 months; and in Class 3 (15 patients), 20 months. In
      univariate testing, age younger than 65 years (p = 0.0004), KPS higher than 70 (p
      = 0.0001), RPA class (p = 0.0078), SIR class (p = 0.0002), and control of the
      primary tumor (p = 0.02) were significantly associated with improved outcome. In
      multivariate analysis, KPS (p < 0.0001), SIR class (p = 0.0008), and RPA class (p
      = 0.03) had statistical value. CONCLUSIONS: This study supports the use of GKRS
      as a single-treatment modality in this selected group of patients. Stratification
      systems are useful in the estimation of patient eligibility for GKRS. A second
      line treatment was necessary in 30% of patients to achieve distal or local brain
      control. This strategy is useful to control brain metastasis in long-surviving
      patients.

PMID- 19095377
TI  - [Comparative study of two single-use vacuum extractor].
AB  - OBJECTIVE: To compare the effectiveness of two single-use vacuum devices, the
      Kiwi Omnicup and the Mitysoft Bell. MATERIAL AND METHODS: This retrospective
      study was conducted during two different periods: from January 15th to March 14th
      to assess the Kiwi Omnicup and from March 15th to June 15th for the Mitysoft
      Bell. The primary outcome was the successful completion of delivery with the
      allocated instrument. Secondary outcomes were fetal scalp trauma and maternal
      perineal lesions. All deliveries were performed by similar teams. RESULTS: Thirty
      nine patients were included in the Kiwi Omnicup group and 48 in the Mitysoft Bell
      group. Compared to the Kiwi Omnicup, the Mitysoft Bell was associated with a
      greater number of cup detachments (41.7% vs. 10.3%; p<0.01) and a significantly
      higher rate of failure (31.3% vs. 12.8%). Rates of substantial scalp trauma and
      maternal trauma were similar in both groups. CONCLUSION: The Mitysoft Bell is not
      as successful at achieving a vaginal delivery as the Kiwi Omnicup. This could be
      explained by the shape of the cup.

PMID- 19095376
TI  - Postoperative external beam radiotherapy for differentiated thyroid cancer:
      outcomes and morbidity with conformal treatment.
AB  - PURPOSE: To review institutional outcomes for patients treated for differentiated
      thyroid cancer with postoperative conformal external beam radiotherapy (EBRT).
      METHODS AND MATERIALS: This is a single-institution retrospective review of 131
      consecutive patients with differentiated thyroid cancer who underwent EBRT
      between January 1996 and December 2005. Histologic diagnoses included 104
      papillary, 21 follicular, and six mixed papillary-follicular types. American
      Joint Committee on Cancer stage distribution was Stage III in 2 patients, Stage
      IVa-IVc in 128, and not assessable in 1. Thirty-four patients (26%) had high-risk
      histologic types and 76 (58%) had recurrent disease. Extraglandular disease
      spread was seen in 126 patients (96%), microscopically positive surgical margins
      were seen in 62 patients (47%), and gross residual disease was seen in 15
      patients (11%). Median EBRT dose was 60 Gy (range, 38-72 Gy). Fifty-seven
      patients (44%) were treated with intensity-modulated radiotherapy (IMRT) to a
      median dose of 60 Gy (range, 56-66 Gy). Median follow-up was 38 months (range, 0
      134 months). RESULTS: Kaplan-Meier estimates of locoregional relapse-free
      survival, disease-specific survival, and overall survival at 4 years were 79%,
      76%, and 73%, respectively. On multivariate analysis, high-risk histologic
      features and gross residual disease predicted for inferior locoregional relapse
      free survival, whereas high-risk histologic features, M1 disease, and gross
      residual disease predicted for inferior disease-specific and overall survival.
      The IMRT did not impact on survival outcomes, but was associated with less
      frequent severe late morbidity (12% vs. 2%). CONCLUSIONS: Postoperative conformal
      EBRT provides durable locoregional disease control for patients with high-risk
      differentiated thyroid cancer if disease is reduced to microscopic burden.
      Patients with gross disease face significantly worse outcomes. The IMRT may
      significantly reduce chronic radiation morbidity, but requires additional study.

PMID- 19095378
TI  - [Place of Streptococcus pyogenes in the throat infection in Morocco and overview
      of its susceptibility to antibiotics].
AB  - OBJECTIVE: In this study we report the prevalence of the throat infections to
      Streptococcus pyogenes in child and adult in Morocco, and the current
      antimicrobial susceptibility of the aminopenicillins and erythromycin. PATIENTS
      AND METHODS: A prospective surveillance study was made from March 2006 to
      February 2007 in four primary health care in Rabat and Sale cities. Six hundred
      and ninety-seven patients (494 children and 203 adults) were the object of
      samplings by throat cotton swab probe, for researching the group A Streptococcus
      (GAS). The patients were those proposed by their doctors for the treatment of
      throat infections. The antimicrobial susceptibility was realized by two methods:
      the disc-diffusion method on Mueller-Hinton agar plates and MICs were determined
      by E-test. The antibiotics tested were the penicillin G, the amoxicillin and the
      erythromycin. RESULTS: S. pyogenes was identified in 65 cases (9.3%): 45 strains
      in children (9.1%) and 20 strains in adults (9.9%). Two peaks of throat
      infections to S. pyogenes were recorded in children aged 12 to 15 years and in
      adults between 36 and 39 years old. All strains were susceptible to penicillin G
      and amoxicillin. One strain was resistant to erythromycin with a MIC greater than
      256 microg/mL.

PMID- 19095380
TI  - Under double influence: assessment of simultaneous alcohol and cannabis use in
      general youth populations.
AB  - BACKGROUND/AIMS: We assessed to what extent adolescents use alcohol and cannabis
      simultaneously and expanded previous research by estimating the proportion of all
      events of cannabis use that had occurred in relation to drinking. How the
      prevalence of this form of polysubstance use co-varied with the overall level of
      alcohol and cannabis use in different countries was also examined. METHOD: We
      analysed individual level data from a survey of 14-20 year-olds in Norway (n=16
      813) and population level data from the 2003 ESPAD study on substance use among
      15-16 year-olds in 35 European countries. RESULTS: The prevalence of simultaneous
      intake of alcohol and cannabis in the past year among Norwegian youth was 7%. The
      overall prevalence of cannabis use was only slightly higher (8%), implying that a
      majority (82%) of the cannabis users had taken the drug in combination with
      alcohol. Moreover, in about 80% of all incidents of cannabis use, alcohol had
      been consumed as well. Correspondingly, a majority of the cannabis users in most
      of the countries in the ESPAD study had used the drug in combination with
      alcohol. Such simultaneous polysubstance use was more prevalent in countries
      where cannabis use was relatively widespread and alcohol rather frequently
      consumed. CONCLUSION: Because adolescents most often combine cannabis with
      alcohol, their use of the drug may be more harmful than assumed. The results also
      indicate that cannabis is a complement rather than a substitute for alcohol,
      suggesting that policies that reduce adolescent drinking may reduce the use of
      cannabis as well.

PMID- 19095379
TI  - Dimensionality of lifetime alcohol abuse, dependence and binge drinking.
AB  - Questions relevant to DSM-V alcohol use disorders (AUD) include whether
      dimensional measures provide more information than categorical diagnoses, whether
      to combine abuse and dependence criteria, and whether to add a new diagnostic
      criterion, binge drinking. Binary and dimensional models of three versions of AUD
      criteria were investigated: (1) dependence criteria; (2) abuse and dependence
      criteria combined; and (3) abuse and dependence criteria combined with a binge
      drinking criterion added. In a national sample of lifetime drinkers (N=27,324),
      these models of AUD criteria were investigated in relation to two well
      established risk factors for AUD, family history and early drinking onset.
      Logistic or Poisson regression modeled the relationships between the validating
      variables and dependence in categorical, dimensional and hybrid forms; Wald tests
      were used to assess differences between the dimensional, categorical and hybrid
      models. Alcohol dependence criteria represented a single continuum (family
      history Wald=9.93, p=0.13; early drinking Wald=7.62, p=0.27) with no support for
      a categorical or hybrid version of alcohol dependence. Adding four abuse criteria
      produced similar results for family history (Wald=15.4, p=0.12) although with
      early drinking, this model showed a trend towards deviating from the data
      (Wald=16.7, p=0.08). No support was found for any diagnostic threshold at 3, 4,
      5, 6, or 7 criteria when abuse and dependence were combined. Adding binge
      drinking resulted in a significant departure from linearity for family history
      (Wald=21.8, p=0.03) and early drinking (Wald=23.9, p=0.01). The number of alcohol
      dependence and abuse criteria met should be explored further as a useful AUD
      severity indicator or phenotype.

PMID- 19095381
TI  - Expression of immunoregulatory genes in peripheral blood mononuclear cells of
      European wild boar immunized with BCG.
AB  - The objective of this study was to analyze the expression of immunoregulatory
      genes in European wild boar (Sus scrofa) immunized with BCG. Eighteen
      immunoregulatory genes were selected for expression analysis based on their role
      in host immune response during tuberculosis and/or for their association with
      resistance to bovine tuberculosis in European wild boar populations. Initially,
      mRNA levels were analyzed by quantitative real-time reverse transcription PCR
      (qRT-PCR) in spleen samples from Mycobacterium bovis-infected (N=18) and
      uninfected (N=22) European wild boar. Statistical analysis of qRT-PCR data
      revealed that four genes, complement component C3, IFN-gamma, IL-4 and RANTES
      were downregulated in infected animals (P<0.05). These genes were selected for
      analysis of mRNA levels in peripheral blood mononuclear cells (PBMCs) from seven
      wild boar experimentally immunized with BCG and seven non-immunized controls.
      Blood was collected at 0, 5, 13 and 25 weeks post-immunization (wpi). The mRNA
      levels of IFN-gamma and C3 showed a peak (>15-fold increase) at 5 wpi, whereas
      transcripts for RANTES and IL-4 showed a peak (>2-fold increase) at 13 wpi in BCG
      immunized animals when compared to non-immunized controls. The pattern of
      expression of these genes over the time provides the first description of BCG
      specific immune response in European wild boar. These results provide new
      insights into the molecular basis of wild boar response to M. bovis infection and
      BCG vaccination and may be used to monitor BCG vaccination in this species.

PMID- 19095382
TI  - Development and validation of a triplex real-time PCR for rapid detection and
      specific identification of M. avium sub sp. paratuberculosis in faecal samples.
AB  - A triplex real-time (TRT-PCR) assay was developed to ensure a rapid and reliable
      detection of Mycobacterium avium subsp. paratuberculosis (Map) in faecal samples
      and to allow routine detection of Map in farmed livestock and wildlife species.
      The TRT-PCR assay was designed using IS900, ISMAP02 and f57 molecular targets.
      Specificity of TRT-PCR was first confirmed on a panel of control mycobacterial
      Map and non-Map strains and on faecal samples from Map-negative cows (n=35) and
      from Map-positive cows (n=20). The TRT-PCR assay was compared to direct
      examination after Ziehl-Neelsen (ZN) staining and to culture on 197 faecal
      samples collected serially from five calves experimentally exposed to Map over a
      3-year period during the sub-clinical phase of the disease. The data showed a
      good agreement between culture and TRT-PCR (kappa score=0.63), with the TRT-PCR
      limit of detection of 2.5 x 10(2)microorganisms/g of faeces spiked with Map. ZN
      agreement with TRT-PCR was not good (kappa=0.02). Sequence analysis of IS900
      amplicons from three single IS900 positive samples confirmed the true Map
      positivity of the samples. Highly specific IS900 amplification suggests therefore
      that each single IS900 positive sample from experimentally exposed animals was a
      true Map-positive specimen. In this controlled experimental setting, the TRT-PCT
      was rapid, specific and displayed a very high sensitivity for Map detection in
      faecal samples compared to conventional methods.

PMID- 19095383
TI  - Bovine papillomavirus type 9 induces epithelial papillomas on the teat skin of
      heifers.
AB  - Experiments were carried out to investigate whether papillomas could be induced
      on the teat skin of heifers by intradermal injection with bovine papillomavirus
      type 9 (BPV-9). Three heifers (#1 and 2, two 0.5-year-old Holsteins; #3, a 1.5
      year-old Japanese Black) were injected with BPV-9 and one heifer (#4, a 0.5-year
      old Holstein) was mock-infected. Viral DNA load in the inocula was quantified by
      real-time polymerase chain reaction assay and adjusted to 1.56x10(12) copies per
      injection. Papillomas appeared at the injection sites in the BPV-9-injected
      heifers #1, 2 and 3 and grew over the 8 (#1 and 2) and 4 (#3)mo observation
      period, respectively. However, no papillomas were found in the mock-infected
      heifer #4. The experimentally induced papillomas were excised and examined.
      Histologically, the lesions were characterized by hyperplasia of the epidermis
      with hyperkeratosis and marked acanthosis and were morphologically similar to
      naturally occurring lesions. BPV-9 DNA and bovine papillomavirus capsid antigen
      were abundant in the lesions. Therefore, we conclude that BPV-9 is an etiological
      agent causing epithelial papillomas on the teat skin of heifers.

PMID- 19095384
TI  - E. coli O157:H7 catabolism of intestinal mucin-derived carbohydrates and
      colonization.
AB  - E. coli O157:H7 colonizes the bovine intestine, can contaminate food through
      fecal shedding, and causes human diarrheal and systemic illnesses. Catabolism of
      particular carbohydrates by E. coli has been found to be important for intestinal
      colonization of mice. In this study, we assessed whether catabolism of two mucin
      derived carbohydrates are important for E. coli O157:H7 colonization of adult
      cattle. This was accomplished by competitively co-colonizing streptomycin-treated
      adult cattle with a wild-type strain of E. coli O157:H7 and isogenic mutants in
      catabolic pathways for mucin-derived carbohydrates N-acetylgalactosamine or l
      fucose. Both mutants colonized poorly compared to the wild-type during the
      initiation stage of colonization (days 0-6). During the maintenance stage of
      colonization (days 7-15), the mutant unable to use N-acetylgalactosamine did not
      show a colonization defect, whereas the strain unable to use fucose had a
      significant colonization defect. These results support the concept that growth
      and colonization of E. coli O157:H7 in the bovine rectum has a nutritional basis,
      with a nutrient preference for l-fucose over N-acetylgalactosamine.

PMID- 19095385
TI  - Survival and developmental competence of buffalo preantral follicles using three
      dimensional collagen gel culture system.
AB  - The aim of the present study was to develop a three-dimensional (3D) collagen gel
      culture system for the in vitro growth and survival of buffalo preantral
      follicles with or without growth factors. Buffalo ovaries were collected from a
      local abattoir and preantral follicles were isolated through microdissection.
      Isolated preantral follicles were put either in collagen gel coated culture dish
      or embedded in a microdrop of collagen gel. The culture medium was TCM-199
      fortified with fetal calf serum (10%), insulin transferin selenium solution (ITS,
      1%), epidermal growth factor (EGF, 20 ng/ml) and follicle stimulating hormone
      (FSH, 0.5 microg/ml). Follicles were divided into three groups and cultured in
      the medium described above (group a, control), with addition of insulin like
      growth factor (IGF-I, 100 ng/ml, group b), or with addition of IGF-I and basic
      fibroblast growth factor (bFGF, 10 ng/ml, group c). Preantral follicles were
      incubated at 38.5 degrees C in 5% CO(2) and maximum humidity. Culture medium was
      replenished after every 72 h and spent medium was stored at -30 degrees C for
      hormone analysis. We found that the extracellular matrix of collagen gel
      maintained follicle viability and growth by providing surface interaction and
      increasing attachment of follicles. Preantral follicles embedded in collagen gel
      droplets had better antrum formation and development as compared to the whole
      surface coated culture method. Follicles cultured with IGF-I on collagen gel
      matrix showed a significantly (P<0.05) higher survival rate and larger mean
      diameter of follicles on day 10 of culture with improved growth and mucification
      as compared to the control group. However, follicles cultured in the combination
      of IGF-I with bFGF had decreased survival rate and smaller mean follicles
      diameter than the IGF-I group (b). Progesterone (P(4)) accumulation was greater
      on day 9 of culture in follicles cultured in IGF-I as compared to control;
      whereas, P(4) was markedly decreased in the combination of IGF-I with bFGF.
      Follicles of the control group could survive for up to 10-15 days before
      degenerating, but follicles cultured with growth factors were able to survive up
      to 20 days and showed signs of early antrum formation. In summary, we have shown
      that collagen gel was a novel and efficacious 3D microenvironment for the
      extended culture of buffalo preantral follicles. Supplementation of culture
      medium with growth factors was found to be essential for antrum formation.

PMID- 19095386
TI  - Effects of Trifolium pratense and Cimicifuga racemosa on the endometrium of
      Wistar rats.
AB  - OBJECTIVE: The aim of this study was to evaluate the effects of Trifolium
      pratense and Cimicifuga racemosa upon the endometrium of castrated female Wistar
      rats, comparing these results with a placebo and estradiol valerate. METHODS:
      Thirty-two adult castrated female Wistar rats were divided into four groups
      (eight rats per group) that receiving either tap water, estradiol valerate,
      isoflavones from T. pratense or deoxyactein from C. racemosa daily. The doses
      used were equivalent to normal doses used in humans. The results were analyzed by
      endometrial histology and the expression of alpha-estrogen receptor and protein
      Ki67. Both alpha-receptor and Ki67 expressions were determined by
      immunohistochemical and morphometric analysis. RESULTS: Endometrium histology
      stayed atrophic with both herbal extracts, but T. pratense supplementation
      increased the expression of alpha-estrogen receptors when compared to the placebo
      group, without protein Ki67 expression enhancement. Both herbal extracts
      presented a lower Ki67 expression when compared to the placebo group. CONCLUSION:
      T. pratense presented alpha-estrogen receptor stimulation in the endometrium
      without increasing cell proliferation. Both herbal extracts reduced endometrial
      proliferation in comparison to the placebo group.

PMID- 19095387
TI  - Freezing skeletal muscle tissue does not affect its decomposition in soil:
      evidence from temporal changes in tissue mass, microbial activity and soil
      chemistry based on excised samples.
AB  - The study of decaying organisms and death assemblages is referred to as forensic
      taphonomy, or more simply the study of graves. This field is dominated by the
      fields of entomology, anthropology and archaeology. Forensic taphonomy also
      includes the study of the ecology and chemistry of the burial environment.
      Studies in forensic taphonomy often require the use of analogues for human
      cadavers or their component parts. These might include animal cadavers or
      skeletal muscle tissue. However, sufficient supplies of cadavers or analogues may
      require periodic freezing of test material prior to experimental inhumation in
      the soil. This study was carried out to ascertain the effect of freezing on
      skeletal muscle tissue prior to inhumation and decomposition in a soil
      environment under controlled laboratory conditions. Changes in soil chemistry
      were also measured. In order to test the impact of freezing, skeletal muscle
      tissue (Sus scrofa) was frozen (-20 degrees C) or refrigerated (4 degrees C).
      Portions of skeletal muscle tissue (approximately 1.5 g) were interred in
      microcosms (72 mm diameter x 120 mm height) containing sieved (2mm) soil (sand)
      adjusted to 50% water holding capacity. The experiment had three treatments:
      control with no skeletal muscle tissue, microcosms containing frozen skeletal
      muscle tissue and those containing refrigerated tissue. The microcosms were
      destructively harvested at sequential periods of 2, 4, 6, 8, 12, 16, 23, 30 and
      37 days after interment of skeletal muscle tissue. These harvests were replicated
      6 times for each treatment. Microbial activity (carbon dioxide respiration) was
      monitored throughout the experiment. At harvest the skeletal muscle tissue was
      removed and the detritosphere soil was sampled for chemical analysis. Freezing
      was found to have no significant impact on decomposition or soil chemistry
      compared to unfrozen samples in the current study using skeletal muscle tissue.
      However, the interment of skeletal muscle tissue had a significant impact on the
      microbial activity (carbon dioxide respiration) and chemistry of the surrounding
      soil including: pH, electroconductivity, ammonium, nitrate, phosphate and
      potassium. This is the first laboratory controlled study to measure changes in
      inorganic chemistry in soil associated with the decomposition of skeletal muscle
      tissue in combination with microbial activity.

PMID- 19095388
TI  - [Vascular surgery; vascular medicine].

PMID- 19095389
TI  - [Venous leiomyosarcoma mimicking deep venous thrombosis: contribution of positron
      emission tomography].
AB  - Leiomyosarcomas are rare malignant mesenchymal tumors. We report the case of a 55
      year-old man with a lung metastasis from an iliofemoral leiomyosarcoma mimicking
      a deep venous thrombosis (DVT). Vascular leiomyosarcoma occurs in the wall of
      large vessels, and usually presents as unexplained DVT. To date, few cases of
      peripheral leiomyosarcomas have been described in the literature. This
      observation demonstrates the usefulness of Positron Emission Tomography (PET),
      beyond oncologic staging, in such indications as the workup of an unexplained
      DVT. In this report, PET prevented a misdiagnosis of DVT by showing a peculiar
      cockade appearance of the vessel. Compared with conventional imaging, PET can
      provide complementary information. The specificity of such information still
      needs to be assessed.

PMID- 19095390
TI  - [Retrospective study of 106 cases of varicella in immunocompetent adults.
      Parameters associated with varicella pneumonia].
AB  - INTRODUCTION: Varicella occurring in healthy adults may extend to the lungs.
      Diagnosing this complication is sometimes difficult because of the discrepancy
      between imaging and clinical presentation usually reported in this affection.
      METHOD: The authors report the result of a retrospective study on 106
      immunocompetent patients including 48 cases of varicella pneumonia. This
      condition is defined as the presence of clinical signs of pneumonia and
      radiological and biological abnormalities consistent with viral pneumonitis.
      RESULTS: Comparison of the patients with or without varicella pneumonia (VP)
      showed that smoking was a risk factor for VP. Other parameters seem to be more
      associated with VP, such as fever greater than 38.3 degrees C, enanthem in the
      mouth, and biological hepatitis. In this study, 29.2% of the patients had
      received nonjustified acyclovir treatment because of missing specific criteria
      for the diagnosis of VP. CONCLUSION: An exact definition of VP and using
      parameters associated to VP would help to specify indication for hospitalization
      and acyclovir treatment. Careful monitoring of healthy patients with varicella is
      essential for an early detection of clinical signs requiring hospitalization.

PMID- 19095391
TI  - Physical-chemical characterization of binary and ternary systems of ketoprofen
      with cyclodextrins and phospholipids.
AB  - Binary and ternary interaction products of ketoprofen (an anti-inflammatory drug
      very poorly water soluble) with phospholipids (phosphatidylcholine (EPC3) and
      phosphatidylglycerol (EPG)) and cyclodextrins (beta-cyclodextrin and its
      methylated derivative (MebetaCd)), were prepared to evaluate their ability in
      improving drug dissolution properties. The different binary and ternary drug
      carrier(s) systems were obtained by microwave irradiation, in order to
      investigate the effectiveness of such a newly proposed preparation technology in
      bringing about effective solid-state interactions among the components. The
      effect of different experimental conditions such as microwave irradiation power
      (500 and 750 W) and treatment time (5, 10 and 15 min) on the physicochemical
      properties of the products has been also assessed. All solid systems were
      characterized by differential scanning calorimetry (DSC) analysis, supported by X
      ray powder diffractometry, and examined for dissolution properties. The study
      pointed out the better performance of ternary systems than the binary ones and
      allowed selection of the best drug-phospholipid-Cd combination and of the most
      effective preparation conditions. In particular drug-EPC3-MebetaCd ternary
      systems obtained by using the greatest microwave irradiation energy and the
      longest treatment time exhibited complete drug amorphization and allowed
      achievement after 60 min of almost 80% dissolved drug, with an increase in
      dissolution efficiency of 10.7 and 1.4 times in comparison with drug alone and
      the corresponding drug-Cd binary system, respectively. The synergistic effect
      between cyclodextrin and phospholipid in enhancing the drug dissolution
      properties has been attributed to the combination of the surfactant properties of
      phospholipids and the wetting and solubilizing power of cyclodextrins and/or the
      possible formation of a "multicomponent" complex.

PMID- 19095392
TI  - Development and validation of an HPLC method for the rapid and simultaneous
      determination of 6-mercaptopurine and four of its metabolites in plasma and red
      blood cells.
AB  - An HPLC method has been developed and validated for the rapid determination of
      mercaptopurine and four of its metabolites; thioguanine, thiouric acid,
      thioxanthine and methylmercaptopurine in plasma and red blood cells. The method
      involves a simple treatment procedure based on deproteinisation by perchloric
      acid followed by acid hydrolysis and heating for 45min at 100 degrees C. The
      developed method was linear over the concentration range studied with a
      correlation coefficient >0.994 for all compounds in both plasma and erythrocytes.
      The lower limits of quantification were 13, 14, 3, 2, 95pmol/8 x 10(8) RBCs and
      2, 5, 2, 3, 20ng/ml plasma for thioguanine, thiouric acid, mercaptopurine,
      thioxanthine and methylmercaptopurine, respectively. The method described is
      selective and sensitive enough to analyse the different metabolites in a single
      run under isocratic conditions. Furthermore, it has been shown to be applicable
      for monitoring these metabolites in paediatric patients due to the low volume
      requirement (200microl of plasma or erythrocytes) and has been successfully
      applied for investigating population pharmacokinetics, pharmacogenetics and non
      adherence to therapy in these patients.

PMID- 19095393
TI  - Identification of multiple constituents in the traditional Chinese medicine
      formula GuiZhiFuLing-Wan by HPLC-DAD-MS/MS.
AB  - GuiZhiFuLing-Wan (GFW) has been used in China for centuries to improve blood
      stagnation. In this paper, a HPLC-DAD-MS/MS method was established for the
      efficient and rapid identification of the chemical constituents in extract of
      GuiZhiFuLing-Wan. Separation was performed on an Alltima C(18) analytical column
      by gradient elution with CH(3)CN/H(2)O-CH(3)COOH as mobile phase at a flow rate
      1.0ml/min. 27 potentially bioactive compounds including monoterpene glycosides,
      galloyl glucoses, acetophenones, phenylallyl compounds and triterpenoids were
      identified or tentatively characterized by online ESI/MS/MS and the comparison
      with literature data and authentic compounds. After the identification, six
      different brands of GFW commercial products in various dosage forms were
      evaluated. The results demonstrated that capsule of GFW was superior to the other
      two dosage forms, honeyed pill and concentrated pill in administration. The
      points that should be paid more attention during the manufacturing process of GFW
      were also analyzed. The method can be the basis for the quality control of this
      commonly used herbal formula.

PMID- 19095394
TI  - Magnesium effect on testosterone-SHBG association studied by a novel molecular
      chromatography approach.
AB  - A biochromatographic approach is developed to measure for the first time
      thermodynamic data and magnesium (Mg(2+)) effect for the binding of testosterone
      (TT) to sex hormone-binding globulin (SHBG) in a wide temperature range. For
      this, the SHBG was immobilized on a chromatographic support. It was established
      that this novel SHBG column was stable during an extended period of time. The
      affinity of TT to SHBG is high and changes slightly with the Mg(2+) concentration
      because the number of Mg(2+) linked to binding is low. The determination of the
      testosterone retention with the steroid hormone at different Mg(2+)
      concentrations and temperatures demonstrated that the Mg(2+) binding heat effect
      associated with this Mg(2+) release or uptake during this binding was in
      magnitude around 17kJ/mol corresponding to the model describing the electrostatic
      attraction that occurs between the negatively charged non specific areas of SHBG
      and the positively charged of magnesium. At all the magnesium concentrations
      studied, the DeltaH values were negative due to van der Waals interactions and
      hydrogen bonding which are engaged at the complex interface confirming strong TT
      SHBG hydrogen bond networks. As well, the DeltaS values were all positive due to
      hydrophobic forces in the testosterone-SHBG complex formation. In addition our
      results suggest that adaptive conformational transitions contribute to the
      specific testosterone-SHBG complex formation. As well, in the biological Mg(2+)
      concentration domain, it was clearly demonstrated that there was an uncompetitive
      inhibition of Mg(2+) on TT-SHBG binding which led an enhancement of bioavailable
      TT. Our work indicated that our biochromatographic approach could soon become
      very attractive for study other SHBG-steroid (or phytoestrogen) binding.

PMID- 19095395
TI  - Determination of mirodenafil and sildenafil in the plasma and corpus cavernous of
      SD male rats.
AB  - The purpose of the present study was to determine sildenafil and a novel PDE-5
      inhibitor, mirodenafil in the plasma and corpus cavernosum tissue of rats to
      compare their pharmacokinetic properties. The concentrations of mirodenafil and
      sildenafil in the rat plasma and corpus cavernosum tissue samples were analyzed
      using LC-MS/MS after a single oral administration at a dose of 40mg/kg to rats.
      Although the T(max), Tlambda(1/2) and MRT were not different between mirodenafil
      and sildenafil, the C(max) and AUC of mirodenafil were significantly higher than
      those of sildenafil in the plasma and corpus cavernosum tissue. Consequently
      mirodenafil remained longer than sildenafil in the plasma and tissue. This may
      provide pharmacokinetic evidence for assessment of the in vivo efficacy of
      mirodenafil and sildenafil.

PMID- 19095396
TI  - Backyard mushroom ingestions: no gastrointestinal decontamination--no effect? Are
      you sure?

PMID- 19095397
TI  - Bland-Altman analysis for determining agreement between two methods.

PMID- 19095398
TI  - Falling ice and snow masses: a rare mechanism of injury.

PMID- 19095400
TI  - Molar pregnancy.

PMID- 19095401
TI  - Pediatric supracondylar fracture.

PMID- 19095403
TI  - C-reactive protein testing does not decrease antibiotic use for acute cough
      illness when compared to a clinical algorithm.
AB  - BACKGROUND: Antibiotics are commonly overused in adults seeking emergency
      department (ED) care for acute cough illness. OBJECTIVE: To evaluate the effect
      of a point-of-care C-reactive protein (CRP) blood test on antibiotic treatment of
      acute cough illness in adults. METHODS: A randomized controlled trial was
      conducted in a single urban ED in the United States. The participants were adults
      (age >= 18 years) seeking care for acute cough illness (<= 21 days duration); 139
      participants were enrolled, and 131 completed the ED visit. Between November 2005
      and March 2006, study participants had attached to their medical charts a
      clinical algorithm with recommendations for chest X-ray study or antibiotic
      treatment. For CRP-tested patients, recommendations were based on the same
      algorithm plus the CRP level. RESULTS: There was no difference in antibiotic use
      between CRP-tested and control participants (37% [95% confidence interval (CI) 29
      45%] vs. 31% [95% CI 23-39%], respectively; p = 0.46) or chest X-ray use (52%
      [95% CI 43-61%] vs. 48% [95% CI 39-57%], respectively; p = 0.67). Among CRP
      tested participants, those with normal CRP levels received antibiotics much less
      frequently than those with indeterminate CRP levels (20% [95% CI 7-33%] vs. 50%
      [95% CI 32-68%], respectively; p = 0.01). CONCLUSIONS: Point-of-care CRP testing
      does not seem to provide any additional value beyond a point-of-care clinical
      decision support for reducing antibiotic use in adults with acute cough illness.

PMID- 19095404
TI  - Cyclosporine diminishes multidrug resistance in K562/ADM cells and improves
      complete remission in patients with acute myeloid leukemia.
AB  - This study was designed to investigate the effects of cyclosporine A (CsA) on a
      multidrug resistance cultured cell line, and its effect on complete remission in
      patients with acute myeloid leukemia (AML). A multidrug resistant K562/ADM cell
      line and drug-sensitive K562 cell line was used. The intracellular concentration
      of daunorubicin and the accumulation of Rhodamine 123 (Rh123) in the K562/ADM and
      K562 cells were evaluated. Clinical effects of CsA were also studied in 65
      patients with AML. In the K562/ADM cells, the 50% of inhibition concentration
      (IC50) of daunorubicin only group was 23.0+/-5.2 micromol/L, which was greater
      than in other groups co-administered with CsA (1.2+/-4.8 micromol/L), verapamil
      (1.5+/-5.4 micromol/L) or CsA+verapamil (1.4+/-4.3 micromol/L) (all P<0.01). The
      relative fluorescence intensity of Rh123 in the K562/ADM cells treated with CsA
      and daunorubicin was increased from 48.9% to 69.8% (P<0.05). CsA also improved
      the complete remission rate in the AML patients (72.7% vs 21.9%, P<0.01). We
      conclude that CsA can significantly diminish the multidrug resistance in K562/ADM
      cells. It also enhances the complete remission rates in patients with AML. CsA
      may be used as an integral part of the chemotherapy for AML.

PMID- 19095405
TI  - Emergency department utilization and determinants of use by 0- to 6-year-old
      children with disabilities in Taipei.
AB  - Although many studies have explored emergency services for children, there are
      few published reports of the utilization of emergency services by children with
      disabilities. The present study attempts to provide data regarding the
      utilization of, and factors affecting, emergency department visits by disabled
      children in Taipei. A general census of 1006 children with disabilities,
      identified from the Taiwan National Disability Registry System in Taipei, was
      conducted. The overall response rate was 38%, yielding a sample of 340 disabled
      children. The results showed that 30.1% of children with disabilities had
      utilized emergency department services over the past 4 months with an average of
      1.4 visits per child. The most common reasons for emergency visits were fever
      (34.7%), respiratory symptoms (24.2%), abdominal pain (15.8%), injury (7.4%), and
      epilepsy seizures (7.4%). This study also found, using a logistic regression
      model, that emergency department utilization may be associated with household
      economic status and the reported physical health of children with disabilities.
      The 'deficit' and 'balance' household economic status groups gave odds ratios of
      3.902 (95% CI=1.469-10.364) and 3.311 (95% CI=1.249-8.779), relative to the
      'surplus' group. The model also indicated that those children with disabilities
      who were reported as being in poor physical health had 11.359 times (95% CI=2.968
      43.469) the likelihood of using emergency care than those whose physical health
      was in excellent condition. The study suggests that in order to maximize the
      health of children with disabilities, medical care stakeholders should consider
      who are the most likely groups to use emergency department services and develop
      anticipatory guidance or preventive services for this vulnerable population.

PMID- 19095406
TI  - Generation and control of cortical gamma: findings from simulation at two scales.
AB  - A continuum model of electrocortical activity was applied separately at
      centimetric and macrocolumnar scales, permitting analysis of interaction between
      scales. State equations included effects of retrograde action potential
      propagation in dendritic trees, and kinetics of AMPA, GABA and NMDA receptors.
      Parameter values were provided from independent physiological and anatomical
      estimates. Realistic field potentials and pulse rates were obtained, including
      resonances in the alpha/theta and gamma ranges, 1/f(2) background activity, and
      autonomous gamma activity. Zero-lag synchrony and travelling waves occurred as
      complementary aspects of cortical transmission, and lead/lag relations between
      excitatory and inhibitory cell populations varied systematically around
      transition to autonomous gamma oscillation. Properties of the simulations can
      account for generation and control of gamma activity. All factors acting on
      excitatory/inhibitory balance controlled the onset and offset of gamma
      oscillation. Autonomous gamma was initiated by focal excitation of excitatory
      cells, and suppressed by laterally spreading trans-cortical excitation, which
      acted on both excitatory and inhibitory cell populations. Consequently, although
      spatially extensive non-specific reticular activation tended to suppress
      autonomous gamma, spatial variation of reticular activation could preferentially
      select fields of synchrony.

PMID- 19095407
TI  - Practical application of contrast-enhanced magnetic resonance mammography [CE
      MRM] by an algorithm combining morphological and enhancement patterns.
AB  - The purpose of this article is to report our practical utilization of dynamic
      contrast-enhanced magnetic resonance mammography [DCE-MRM] in the diagnosis of
      breast lesions. In many European centers, was preferred a high-temporal
      acquisition of both breasts simultaneously in a large FOV. We preferred to scan
      single breasts, with the aim to combine the analysis of the contrast intake and
      washout with the morphological evaluation of breast lesions. We followed an
      interpretation model, based upon a diagnostic algorithm, which combined contrast
      enhancement with morphological evaluation, in order to increase our confidence in
      diagnosis. DCE-MRM with our diagnostic algorithm has identified 179 malignant and
      41 benign lesions; final outcome has identified 178 malignant and 42 benign
      lesions, 3 false positives and 2 false negatives. Sensitivity of CE-MRM was
      98.3%; specificity, 95.1%; positive predictive value, 98.9%; negative predictive
      value, 92.8% and accuracy, 97.7%.

PMID- 19095408
TI  - X-ray angiogram images enhancement by facet-based adaptive anisotropic diffusion.
AB  - The paper presents a versatile nonlinear diffusion method to visually enhance the
      angiogram images for improving the clinical diagnosis. Traditional nonlinear
      diffusion has been shown very effective in edge-preserved smoothing of images.
      However, the existing nonlinear diffusion models suffer several drawbacks:
      sensitivity to the choice of the conductance parameter, limited range of edge
      enhancement, and the sensitivity to the selection of evolution time. The new
      anisotropic diffusion we proposed is based on facet model which can solve the
      issues mentioned above adaptively according to the image content. This method
      uses facet model for fitting the image to reduce noise, and uses the sum square
      of eigenvalues of Hessian as the standard of the conductance parameter selection
      synchronously. The capability of dealing with noise and conductance parameter can
      also change adaptively in the whole diffusion process. Moreover, our method is
      not sensitive to the choice of evolution time. Experimental results show that our
      new method is more effective than the original anisotropic diffusion.

PMID- 19095409
TI  - Sialolithiasis in a stump of Wharton's duct of an aplastic unilateral
      submandibular gland.
AB  - Congenital absence of the salivary glands is an uncommon disorder. Isolated
      aplasia of a unilateral submandibular gland is rare and only 6 cases have been
      reported. The formation of a sialolith within the remaining Wharton's duct,
      associated with isolated aplasia of a unilateral submandibular gland, has not
      been reported previously. The authors report two cases of sialolithiasis within
      the ipsilateral remaining Wharton's duct in patients with isolated aplasia of a
      unilateral submandibular gland.

PMID- 19095411
TI  - Tackling multiple antibiotic resistance in enteropathogenic Escherichia coli
      (EPEC) clinical isolates: a diarylheptanoid from Alpinia officinarum shows
      promising antibacterial and immunomodulatory activity against EPEC and its
      lipopolysaccharide-induced inflammation.
AB  - Antibiotic treatment for infectious diseases commonly leads to host inflammatory
      responses. Molecules with bifunctional antibacterial and anti-inflammatory
      properties could provide a solution for such clinical manifestations. Here we
      report such bifunctional activity for a diarylheptanoid (5-hydroxy-7-(4''-hydroxy
      3-methoxyphenyl)-1-phenyl-3-heptanone) isolated from Alpinia officinarum, a
      medicinal plant belonging to the Zingiberaceae family, against enteropathogenic
      Escherichia coli (EPEC). The diarylheptanoid showed inhibitory and bactericidal
      activity against EPEC clinical isolates and efficiently suppressed EPEC
      lipopolysaccharide-induced inflammation in human peripheral blood mononuclear
      cells. In silico docking analysis revealed that the diarylheptanoid could
      interact with subunit A of E. coli DNA gyrase. Such molecules with bifunctional
      activity may be potential therapeutics for infectious diseases.

PMID- 19095412
TI  - Allicin enhances the oxidative damage effect of amphotericin B against Candida
      albicans.
AB  - Amphotericin B (AmB) is the gold standard of antifungal treatment for the most
      severe invasive mycoses. In addition to the interaction of AmB with ergosterol in
      the fungi cell membrane, several studies have demonstrated oxidative damage
      involved in the fungicidal activity of AmB. In this study, allicin, an allyl
      sulphur compound from garlic, was shown to enhance significantly the effect of
      AmB against Candida albicans in vitro and in vivo, although allicin did not exert
      a fungicidal effect. Further study first demonstrated that allicin-mediated
      oxidative damage, such as phospholipid peroxidation in the plasma membrane, via
      influencing the defence of C. albicans against oxidative damage may be the cause
      of the synergistic interaction between allicin and AmB. We envision that a
      combination of AmB with allicin may prove to be a promising strategy for the
      therapy of disseminated candidiasis.

PMID- 19095413
TI  - Effects of tea tree (Melaleuca alternifolia) oil on Staphylococcus aureus in
      biofilms and stationary growth phase.
AB  - Tea tree oil (TTO) is known for its antimicrobial activity. In this study, we
      determined whether TTO is effective against Staphylococcus aureus in biofilms and
      how TTO activity is affected by the S. aureus growth phase. All clinical strains
      tested were killed by TTO both as planktonic cells and as biofilms. The minimum
      biofilm eradication concentration was usually two times higher than the minimum
      bactericidal concentration, yet it was never higher than 1% v/v. The fastest
      killing of biofilm occurred during the first 15min of contact with TTO and was
      not influenced by increasing TTO concentration above 1% v/v. Planktonic
      stationary phase cells exhibited decreased susceptibility to TTO compared with
      exponential phase cells. The killing rate for stationary phase cells was also
      less affected by increasing TTO concentration than that for exponential phase
      cells. These data show that TTO efficiently kills S. aureus in the stationary
      growth phase and within biofilms and is therefore a promising tool for S. aureus
      eradication.

PMID- 19095410
TI  - Driving cost factors in adult outpatients with refractory epilepsy: a daily
      clinical practice in clinics of neurology in Spain.
AB  - OBJECTIVE: To explore the association between patient-reported-outcomes
      measurements and costs in adult outpatients with drug refractory epilepsy (DRE)
      in Spain. METHODS: Secondary analysis of a cross-sectional study to determine
      resources utilization and related costs of refractory epilepsy in Spain (LINCE
      study). Consecutive adult outpatients fulfilling criteria for DRE were analyzed.
      Health-related quality of life (HRQoL), anxiety and depression, self-perceived
      health status and patient's satisfaction with treatment were assessed
      respectively by QOLIE-10, HAD scales, EQ-5D-VAS and SATMED-Q questionnaire. Costs
      were estimated from public tariffs computing healthcare and non-healthcare
      resources use in the year 2005. RESULTS: Seven hundred sixty two consecutive
      patients (728 (95.5%) valuables; 50.8% males, 40.5+/-13.5 years) were analyzed.
      Severe levels of anxiety and depression were both associated with higher costs:
      from a mean yearly total cost of 6291 euros +/- 7748 (no anxiety) to 10325.8
      euros +/-9900.8 (severe), p<0.0012 and from 5983.5 euros +/-6726.1 (no
      depression) to 12691.4 euros +/-11745.9 (severe), p<0.0001. Total yearly cost was
      inversely associated with HRQoL, self-perceived health status and satisfaction
      with treatment: from 11517.3 euros +/-11449.2 to 5430.2 euros +/-7776.6, first
      and tenth QOLIE-10 decile intervals, respectively, from 11494 euros +/- 11668 to
      5334.3 +/- 7606, first and tenth VAS decile intervals, respectively, and from
      9762.6 euros +/- 9956.6 to 4746.4 euros +/- 5616.7, first and tenth SATMED-Q
      decile intervals, respectively, p<0.0001. CONCLUSIONS: Higher costs of refractory
      epilepsy were associated with poorer patient-reported-outcomes scores. These
      findings may be of interest for both health decision makers and clinicians when
      evaluating the resources devoted to epilepsy.

PMID- 19095414
TI  - In vitro activity of nadifloxacin against several Gram-positive bacteria and
      analysis of the possible evolution of resistance after 2 years of use in Germany.
AB  - Nadifloxacin has good activity against Propionibacterium acnes as well as against
      both meticillin-susceptible and -resistant Staphylococcus aureus (MSSA and MRSA,
      respectively) and Staphylococcus epidermidis. The aim of this study was to
      evaluate the activity of this fluoroquinolone against the abovementioned
      microorganisms, comparing isolates collected in 2007 in Germany, a country where
      nadifloxacin has been used for the last 2 years, with isolates collected from
      2006-2007 in Spain where nadifloxacin has not been used. A collection of P. acnes
      from Hungary (strains collected during 2005-2006) and a collection of P. acnes
      from different countries in Europe (collected during 2002) were also included.
      The activity of nadifloxacin was compared with ciprofloxacin, erythromycin and
      clindamycin. Susceptibility testing of P. acnes was performed by agar dilution,
      whereas the susceptibility of the different staphylococci was determined by
      microdilution. Although the isolates were collected from three different
      countries (Spain, Hungary and Germany) where the use of quinolones can produce a
      different effect, no significant differences in the percentages of resistance to
      nadifloxacin were observed in P. acnes, MSSA, MRSA and S. epidermidis. Therefore,
      topical antibiotics such as nadifloxacin do not have an additional effect on
      resistance. Moreover, nadifloxacin presented much better activity than the
      comparator drugs used in this study against the studied microorganisms.

PMID- 19095415
TI  - Spread of multidrug-resistant Proteus mirabilis isolates producing an AmpC-type
      beta-lactamase: epidemiology and clinical management.
AB  - A remarkable increase in Proteus mirabilis strains producing acquired AmpC-type
      beta-lactamases (CBLs) has been observed at Ospedale di Circolo e Fondazione
      Macchi (Varese, Italy) over the last few years. The epidemiology and treatment
      outcome of infections associated with this unprecedented spread are reported.
      From 2004-2006, 2070 P. mirabilis isolates were investigated. Extended-spectrum
      beta-lactamases (ESBLs) and CBL resistance determinants were identified by gene
      amplification and direct sequencing. Clonal relatedness was evaluated by
      macrorestriction analysis. Overall, 43 CBL-positive isolates were obtained from
      hospitalised (n=22) and non-hospitalised (n=21) patients (median age 78.8 years).
      The prevalence of CBL-positive isolates increased from 0.3% in 2004 to 4.6% in
      2006, whereas that of ESBL-positive isolates remained constant (ca. 10%). CBL
      positive isolates were multidrug-resistant and carried the CMY-16 determinant.
      All but two isolates were genetically identical or closely related. Retrospective
      analysis of clinical records revealed that the majority of CMY-16-positive
      isolates were associated with urinary tract infections. Treatment with amikacin
      or carbapenems was consistently effective, whereas piperacillin/tazobactam
      produced a clinical response in seven of nine cases. This is the first report of
      a rapid spread of CBL-positive P. mirabilis strains endowed with remarkable
      antimicrobial resistance. Practical methods for CBL detection are needed for the
      appropriate management of related infections.

PMID- 19095416
TI  - Metallo-beta-lactamases in Gram-negative bacteria: introducing the era of pan
      resistance?
AB  - Metallo-beta-lactamases (MBLs) are being reported with increasing frequency and
      from several countries worldwide and are becoming the prevalent and most
      clinically significant determinants of carbapenem resistance. Furthermore, MBL
      producing strains that exhibit a pan-resistant phenotype are increasingly
      detected. Initially MBLs were detected in Pseudomonas aeruginosa, however
      nowadays they are frequently found in Acinetobacter baumannii, Klebsiella
      pneumoniae and other Enterobacteriaceae. MBLs spread easily on plasmids and cause
      nosocomial infections and outbreaks with excess mortality. Such infections mainly
      concern patients admitted to Intensive Care Units with several co-morbidities and
      a history of prolonged administration of antibiotics. MBL-producing strains
      exhibit resistance to almost all currently available antibiotics. In vitro
      studies reveal that tigecycline and colistin are the only antibacterial agents
      with consistent activity against MBL-producing strains. Randomised controlled
      trials are required in order to evaluate the available therapeutic regimens,
      including treatment combinations. Tigecycline and colistin should be used under
      appropriate prescribing practices. Surveillance to monitor the emergence of
      resistance to these agents as well as implementation of infection control
      measures should be strengthened. MBL inhibitors are urgently needed, however,
      none is in late pre-clinical development.

PMID- 19095417
TI  - Comparative susceptibilities of hepatitis A virus, feline calicivirus,
      bacteriophage MS2 and bacteriophage PhiX-174 to inactivation by quaternary
      ammonium and oxidative disinfectants.

PMID- 19095418
TI  - Pharmacokinetic-pharmacodynamic target attainment analysis of doripenem in
      infected patients.
AB  - This study was a pharmacokinetic (PK)-pharmacodynamic (PD) target attainment
      analysis of doripenem. Drug concentration data in plasma (115 samples) and urine
      (61 samples) from 18 infected patients were concurrently analysed to develop a
      more accurate population PK model for doripenem. In the final PK model,
      creatinine clearance (CL(Cr)) was the most significant covariate: CL(r)
      (L/h)=0.137xCL(Cr); CL(nr) (L/h)=2.49; V(1) (L)=8.29; Q (L/h)=8.10; and V(2)
      (L)=9.37, where CL(r) and CL(nr) are the renal and non-renal clearances, V(1) and
      V(2) are the volumes of distribution of the central and peripheral compartments,
      and Q is the intercompartmental (central-peripheral) clearance. Based on the PK
      model, a Monte Carlo simulation predicted the probabilities of attaining the
      bactericidal exposure target (40% of the time above the minimum inhibitory
      concentration (MIC)) in plasma and defined the PK-PD breakpoints (the highest MIC
      values at which the target attainment probabilities were >or=90%). The breakpoint
      for 500 mg every 8h (q8h) (1-h infusion) with a CL(Cr) of 80 mL/min (1 microg/mL)
      corresponded to those for 250 mg q8h with a CL(Cr) of 40 mL/min and 250 mg every
      12h with a CL(Cr) of 20 mL/min. Prolonging the infusion time was a more effective
      strategy than dose escalation to increase the breakpoint. These results provide
      guidance for constructing a PK-PD-based strategy for dosing guidance for
      tailoring doripenem regimens.

PMID- 19095419
TI  - Consecutive human bifidobacteria isolates and acquired tet genes.

PMID- 19095420
TI  - Linezolid pharmacodynamics with Staphylococcus aureus in an in vitro dynamic
      model.
AB  - To describe the relationship between the ratio of the 24-h area under the
      concentration-time curve (AUC(24)) to minimum inhibitory concentration (MIC) as
      well as the effect of linezolid on Staphylococcus aureus, the killing kinetics of
      three S. aureus strains was studied by in vitro simulation of 5-day antibiotic
      dosing over a wide range of AUC(24)/MIC ratios. Similarly susceptible meticillin
      resistant S. aureus ATCC 43300 and S. aureus 479 and vancomycin-intermediate S.
      aureus ATCC 700699 (Mu50) at a starting inoculum of 10(8) colony-forming units
      (CFU)/mL were exposed to multiple-dose pharmacokinetics of twice-daily linezolid
      for 5 days. The simulated AUC(24)/MIC ratios varied from 30 h to 1200 h (S.
      aureus ATCC 43300), from 30h to 600 h (S. aureus 479) and from 50h to 400 h (S.
      aureus ATCC 700699). The cumulative antimicrobial effect was expressed by its
      intensity (I(E)) measured from the start of treatment to the time after the last
      antibiotic dose when numbers of antibiotic-exposed bacteria reached
      >or=10(8)CFU/mL. With each organism, bacterial re-growth followed a pronounced
      reduction of the starting inoculum that occurred at each simulated AUC(24)/MIC
      ratio except for the lowest value (30 h). This reduction was AUC(24)/MIC
      dependent: the minimum numbers of surviving organisms decreased with increasing
      AUC(24)/MIC ratios. A sigmoid relationship was established between I(E) and the
      simulated AUC(24)/MIC ratio. This relationship was bacterial strain-independent;
      a logistic function fits the combined data with r(2)=0.95. The established
      AUC(24)/MIC-I(E) relationship is useful to predict the antistaphylococcal effects
      of linezolid at clinically attainable AUC(24)/MIC values.

PMID- 19095421
TI  - The EQ-5D: A useful quality of life measure in borderline personality disorder?
AB  - INTRODUCTION: Borderline Personality Disorder (BPD) is a severe psychiatric
      disorder and is associated with significant impairment in quality of life. The
      aim of the present study is to assess the internal and external responsiveness of
      the EuroQoL-5D (EQ-5D) in BPD patients. PATIENTS AND METHODS: Data from 49
      patients included in a multi-center Dutch randomized trial were used. We used
      both the EQ-5D utility score and the Visual Analogue Scale of the EuroQoL, and
      the Borderline Personality Disorder Severity Index-IV (BPDSI-IV). To determine
      internal responsiveness, we calculated the standardized response mean (SRM). To
      determine external responsiveness, we calculated Spearman correlations for the
      change scores, and compared EQ-5D scores for clinically improved vs. non
      clinically improved patients as measured with the BPDSI-IV. RESULTS: Patient
      scores improved on all instruments during the three years. SRMs for BPDSI-IV were
      significantly higher than EQ-5D utility. Three-year Spearman correlation between
      change scores of BPDSI-IV and EQ-5D utility was 0.487, between BPDSI-IV and EQ
      VAS it was 0.404, both statistically significant. EQ-5D utility scores for
      patients who clinically improved were significantly higher than for patients who
      did not. DISCUSSION: We conclude that the EQ-5D is fairly responsive in BPD, and,
      therefore, especially because of its brevity and user-friendliness, can serve as
      a useful tool in economic evaluations in patients with BPD.

PMID- 19095422
TI  - Cuttlebone-derived organic matrix as a scaffold for assembly of silver
      nanoparticles and application of the composite films in surface-enhanced Raman
      scattering.
AB  - Biologically derived materials provide a rich variety of approaches toward new
      functional materials because of their fascinating structures and environment
      friendly features, which is currently a topic of research interest. In this
      paper, we show that the cuttlebone-derived organic matrix (CDOM) is an excellent
      scaffold for the one-step synthesis and assembly of silver nanoparticles (AgNPs),
      which can be further used as substrate for surface-enhanced Raman scattering
      (SERS). Formation of AgNPs-CDOM composite was accomplished by the reaction of
      CDOM with AgNO(3) and NH(3).H(2)O solution at 80 degrees C without using any
      other stabilizer and reducing agents. UV-vis spectra and TEM were utilized to
      characterize the AgNPs and investigate their formation process. Results
      demonstrate that the size and distribution of AgNPs can be partly regulated by
      changing incubation time; the concentration of NH(3).H(2)O is critical to the
      formation rate of AgNPs. As a proof of principle, we show that the AgNPs-CDOM
      composite can be employed in trace analysis using SERS.

PMID- 19095423
TI  - Immobilization of proteins on metal ion chelated polymer surfaces.
AB  - Over the last decade, the chelator-based strategy for protein immobilization has
      received considerable attention. Here, we describe a stepwise approach for the
      modification of polyurethane (PU) surfaces which involves the introduction of a
      poly(ethylene glycol) (PEG) layer to shield the PU substrate surface against
      nonspecific protein adsorption and a chelator head (quinolin-8-ol, HQ), to
      provide relatively high-target protein binding capacity. The surface properties,
      the immobilization of proteins on the surface, and the bioactivity of the
      immobilized proteins were investigated by various techniques. It was demonstrated
      that this approach provides a powerful means for surface immobilization of
      proteins with high density, with a homogeneous distribution and retaining the
      bioactivity of the immobilized proteins.

PMID- 19095424
TI  - [Videogames risks: diagnosis and management].
AB  - Videogames accompany teenagers from childhood to adulthood, because they are the
      stage of their fantasies and hopes. But they are dangerous when teenagers are
      insecure, when they have lived early sufferings, or when they have a bad self
      esteem. Doctor must in the same time advice the parents, and appreciate the
      gravity.

PMID- 19095425
TI  - [Vaccination coverage among health care workers in the pediatric emergency and
      intensive care department of Edouard Herriot hospital in 2007, against influenza,
      pertussis, varicella, and measles].
AB  - AIM: The aim of this study was to determine the vaccination coverage among the
      medical and paramedical health care workers of the pediatric intensive care and
      emergency department of Edouard Herriot hospital in Lyon, with respect to
      influenza, pertussis, varicella, and measles, 4 diseases with air transmission
      and vaccination recommendations. METHOD: During February and March 2007, a
      questionnaire was given by hand to 123 health care workers by a medical student
      working there or available in the intensive care unit. RESULTS: The response rate
      to the questionnaire was 68.3%. The vaccination coverage against influenza was
      42.8%; men and medical health care workers were better vaccinated. With respect
      to vaccination against pertussis, one third had received an injection in
      adulthood, adults under age 30 and medical health care workers were better
      vaccinated, but the difference was not statistically significant. Ten health care
      workers were not vaccinated and had no history of measles: only 1 had had a
      measles serology and none were vaccinated. Eleven had no history of varicella: 6
      had had a varicella serology and none were vaccinated. CONCLUSIONS: Vaccination
      coverage against influenza is higher than what has been reported in the
      literature, possibly because of a mobile vaccination campaign against influenza
      made during winter 2006 in this pediatric department. Vaccination coverage
      against pertussis is encouraging and probably the consequence of an awareness of
      the gravity of the disease among infants. Individual information is necessary for
      health care workers on the nosocomial risk for influenza and pertussis in
      infants, and vaccination must be proposed. Serology against varicella and measles
      is compulsory for all health care workers with no history and no vaccination
      against these 2 diseases, to track and vaccinate the nonimmunized personnel.
      Occupational physicians have a very important role to play in meeting this goal.

PMID- 19095426
TI  - [Recurrent infection in a child caused by Job-Buckley syndrome].

PMID- 19095427
TI  - Situated cognition in clinical visualization: the role of transparency in
      GammaKnife neurosurgery planning.
AB  - OBJECTIVE: The aim of this study was to investigate how the clinical use of
      visualization technology can be advanced by the application of a situated
      cognition perspective. METHODS AND MATERIALS: The data were collected in the
      GammaKnife radiosurgery setting and analyzed using qualitative methods.
      Observations and in-depth interviews with neurosurgeons and physicists were
      performed at three clinics using the Leksell GammaKnife. RESULT: The users'
      ability to perform cognitive tasks was found to be reduced each time
      visualizations incongruent with the particular user's perception of clinical
      reality were used. The main issue here was a lack of transparency, i.e. a black
      box problem where machine representations "stood between" users and the cognitive
      tasks they wanted to perform. For neurosurgeons, transparency meant their
      previous experience from traditional surgery could be applied, i.e. that they
      were not forced to perform additional cognitive work. From the view of the
      physicists, on the other hand, the concept of transparency was associated with
      mathematical precision and avoiding creating a cognitive distance between basic
      patient data and what is experienced as clinical reality. The physicists
      approached clinical visualization technology as though it was a laboratory
      apparatus--one that required continual adjustment and assessment in order to
      "capture" a quantitative clinical reality. CONCLUSION: Designers of visualization
      technology need to compare the cognitive interpretations generated by the new
      visualization systems to conceptions generated during "traditional" clinical
      work. This means that the viewpoint of different clinical user groups involved in
      a given clinical task would have to be taken into account as well. A way forward
      would be to acknowledge that visualization is a socio-cognitive function that has
      practice-based antecedents and consequences, and to reconsider what analytical
      and scientific challenges this presents us with.

PMID- 19095428
TI  - Diabetes-linked zinc transporter ZnT8 is a homodimeric protein expressed by
      distinct rodent endocrine cell types in the pancreas and other glands.
AB  - BACKGROUND AND AIMS: Zinc is abundant in pancreas, being required by endocrine
      islet cells for hormone secretion and by exocrine acinar cells as pancreatic
      juice component. ZnT8 is a member of the SLC30A family of zinc transporters whose
      overexpression in cultured pancreatic beta cells leads to increased insulin
      secretion in response to glucose, suggesting a possible role in regulating
      glycemia. ZnT8 was therefore proposed as a therapeutic target for diabetes, and
      recent genome-wide association studies identified polymorphisms in the ZNT8 gene
      conferring increased type 2 diabetes risk. METHODS AND RESULTS: As limited
      information was available on the biochemical properties of ZnT8 and on its
      endogenous expression, we have raised a specific polyclonal antibody and
      immunostained protein extracts, cell lines and tissue sections. We show that ZnT8
      forms a very stable dimer that requires biological membranes to properly
      assemble. We demonstrate localization of murine ZnT8 to the secretory granules in
      pancreatic beta and alpha islet cells. Moreover, we show that ZnT8 is also
      expressed in other secretory cell types, namely the cubical epithelium that lines
      thyroid follicles and the cortex of the adrenal gland, suggesting a more
      widespread role in endocrine secretion. CONCLUSION: We provide novel insights
      into the features of the ZnT8 transporter, of special relevance in light of its
      proposed role as therapeutical target for diabetes treatment.

PMID- 19095429
TI  - The thalidomide analog 3-phthalimido-3-(3,4-dimethoxyphenyl)-propanoic acid
      improves the biliary cirrhosis in the rat.
AB  - Chronic cholestasis and cholangitis may lead to the last phase known as biliary
      cirrhosis, characterized by cellular necrosis, apoptosis, tissue damage, local
      regeneration, inflammation and fibrosis. Such events are mediated by cytokines.
      Thalidomide and its analogs have shown to be effective immunomodulatory and
      hepatoprotective agents. The aim of this work was to evaluate the
      hepatoprotective properties of a thalidomide analog, the 3-phthalimido-3-(3,4
      dimethoxyphenyl)-propanoic acid (PDA), on bile duct obstruction-induced
      cirrhosis. Vehicle or PDA (67 mg/kg) was orally administered twice a day to sham
      (Sham) or bile duct-ligated (BDL) male Wistar rats. The animals were sacrificed
      28 days after treatments. Alkaline phosphatase (AP), gamma-glutamyl
      transpeptidase (GGTP) and alanine aminotransferase (ALT) enzyme activities as
      well as direct and total bilirubins concentration were determined in plasma.
      Lipid peroxidation (LP), glycogen and collagen were quantified in liver; in
      addition, histopathology was performed. PDA improved cholestasis, necrosis and
      fibrosis by significantly diminishing most of liver injury markers (P<0.05).
      Histopathology also showed remarkable liver damage amelioration. PDA
      effectiveness may be due to its water-solubility, stability, phosphodiesterase-4
      inhibitory and immunomodulatory actions. Thalidomide and its analogs seem to be
      promising drugs for further treatment of biliary cirrhosis.

PMID- 19095431
TI  - Effect of exposure test conditions on leaching behavior of inorganic contaminants
      from recycled materials for roadbeds.
AB  - Throughout the utilization of recycled materials, weathering factors such as
      humidity, gas composition and temperature have the potential to change the
      material properties and enhance the release of inorganic contaminants. In this
      research, the effects of weathering factors on recycled gravel materials for
      roadbeds were evaluated by applying three kinds of accelerating exposure tests:
      freezing-melting cycle test, carbonation test, and dry-humid cycle test. The
      effects of exposure tests were determined by X-ray diffraction (XRD) analysis and
      serial batch leaching test, making it possible to identify the change in release
      mechanisms. Sixteen elements, mainly metals, were investigated. Tested samples
      were molten slag from municipal solid waste, molten slag from automobile shredded
      residue, and crushed natural stone. After the exposure tests, the increase of
      cumulative release in the leaching test was generally less than 2.0 times that of
      the samples without the exposure test. Among the three test conditions, freezing
      melting showed a slightly higher effect of enhancing the release of constituents.
      XRD analysis showed no change in chemical species. From these results, it was
      determined that the stony samples were stable enough so that their properties
      were not significantly changed by the exposure tests.

PMID- 19095430
TI  - Liquid chromatography tandem mass spectrometry identification of
      proanthocyanidins in rat plasma after oral administration of grape seed extract.
AB  - Proanthocyanidin rich plant extracts derived from grape seed extract (GSE),
      hawthorn and cranberry are on markets for their preventive effects against
      cardiovascular diseases and uroinfections in woman. However, the importance of
      these health beneficial effects of these botanicals remains elusive due to
      incomplete understanding of uptake, metabolism and bioavailability of
      proanthocyanidins in vivo. In the present study rats were given GSE orally (300
      mg/kg, twice a day) and blood and urine were collected over a 24 h period.
      Monomeric catechins and their methylated metabolites, and proanthocyanidins up to
      trimers were detected in blood samples treated with GSE using LC-MS/MS operating
      in the multiple reaction monitoring (MRM) mode. A new tetramethylated metabolite
      of dimeric proanthocyanidin (m/z 633) in GSE-treated urine was tentatively
      identified. Using LC-MS/MS, (+)-catechin and (-)-epicatechin were identified in
      the brain conclusively. These data suggested that GSE catechins cross the blood
      brain barrier and may be responsible for the neuroprotective effects of GSE.

PMID- 19095432
TI  - Long range surface plasmon-enhanced fluorescence spectroscopy for the detection
      of aflatoxin M1 in milk.
AB  - A novel biosensor for the highly sensitive detection of aflatoxin M(1) (AFM(1))
      in milk was developed. This biosensor is based on surface plasmon-enhanced
      fluorescence spectroscopy (SPFS) which was advanced through the excitation of
      long range surface plasmons (LRSPs). In SPFS, the binding of fluorophore-labeled
      molecules to the sensor surface is probed with surface plasmons (SPs) and the
      emitted fluorescence light is detected. This approach takes advantages of the
      enhanced intensity of electromagnetic field occurring upon the resonant
      excitation of SPs which directly increases the fluorescence signal. For the
      detection of AFM(1), LRSP-enhanced fluorescence spectroscopy was combined with an
      inhibition immunoassay in which a derivative of AFM(1) was immobilized on the
      sensor surface and antibodies against AFM(1) were used as recognition elements.
      The developed biosensor allowed for the detection of AFM(1) in milk within 53min
      at concentrations as low as 0.6pgmL(-1). The achieved limit of detection was
      about two orders of magnitude lower than the maximum AFM(1) residue level in milk
      stipulated by the European Commission legislation.

PMID- 19095433
TI  - Genomic analysis of cichlid fish 'natural mutants'.
AB  - In the lakes of East Africa, cichlid fishes have formed adaptive radiations that
      are each composed of hundreds of endemic, morphologically stunningly diverse, but
      genetically extremely similar species. In the past 20 years, it became clear that
      their extreme phenotypic diversity arose within very short time spans, and that
      phenotypically radically different species are exceptionally similar genetically;
      hence, they could be considered to be 'natural mutants'. Many species can be
      hybridized and, therefore, provide a unique opportunity to study the genetic
      underpinnings of phenotypic diversification. Comparative large-scale genomic
      analyses are beginning to unravel the patterns and processes that led to the
      formation of the cichlid species flocks. Cichlids are an emerging evolutionary
      genomic model system for fundamental questions on the origin of phenotypic
      diversity.

PMID- 19095434
TI  - Rapidly evolving fish genomes and teleost diversity.
AB  - Teleost fishes are the largest and most diverse group of vertebrates. The
      diversity of teleosts has been attributed to a whole-genome duplication (WGD)
      event in the ray-finned fish lineage. Recent comparative genomic studies have
      revealed that teleost genomes have experienced frequent gene-linkage disruptions
      compared to other vertebrates, and that protein-coding sequences in teleosts are
      evolving faster than in mammals, irrespective of their duplication status. A
      significant number of conserved noncoding elements (CNEs) shared between
      cartilaginous fishes and tetrapods have diverged beyond recognition in teleost
      fishes. The divergence of CNEs seems to have been initiated in basal ray-finned
      fishes before the WGD. The fast evolving singleton and duplicated genes as well
      as the divergent CNEs might have contributed to the diversity of teleost fishes.

PMID- 19095435
TI  - Implicit online corrections of reaching movements.
AB  - Many neuroscience studies of arm control have attempted to explain how aimed
      movements are planned, generated, and corrected. The mechanisms of subconscious
      online reaching correction to a target shift are now being widely examined from
      computational, physiological, and pathological viewpoints. Recent evidence of a
      quick manual response to surrounding visual motion suggests an additional online
      compensatory mechanism in reaching movements for bodily and/or external
      environmental changes, although the computational principle underlying this
      process remains controversial. Together with preprogrammed voluntary motor
      command generation, it appears that multiple online visually guided correction
      mechanisms implicitly govern reaching control to bring the hand to the goal. It
      is important to reveal unknown mechanisms and underlying neural substrates of
      generating the response to visual motion, which is additionally modulated by
      action contexts.

PMID- 19095436
TI  - The predictive value of interleukin-8 (IL-8) in hospitalised patients with fever
      and chemotherapy-induced neutropenia.
AB  - AIM: To demonstrate whether serum Interleukin-8 (IL-8) is a relevant parameter to
      select hospitalised patients with chemotherapy-induced neutropenic fever with low
      or high probability of infection. RESULTS: 90 assessable febrile episodes in 73
      patients were evaluated; 46% of the febrile episodes were microbiologically
      documented infection (MDI), 8% clinical documented infection (CDI), and 47% fever
      of unknown origin (FUO). Median IL-8 level was lower in the FUO group compared to
      CDI and MDI (p<0.0005). In 45 of 48 episodes (94%) with CDI/MDI, IL-8 level at
      the start was > or =60 ng/l while in 18 of 21 episodes (86%) with IL-8 level <60
      ng/l, no infectious cause was demonstrated. FUO and CDI/MDI patients with IL-8 >
      or =60 ng/l and responsive on antibiotic treatment showed a decline of IL-8
      levels within days in contrast to non-responding patients. CONCLUSIONS: Serum IL
      8 level can be a useful marker to identify hospitalised FUO patients with low
      probability of infection.

PMID- 19095437
TI  - Individual patient data analysis to assess modifications to the RECIST criteria.
AB  - BACKGROUND: After the initial RECIST 1.0 were published in 2000, the criteria
      were widely implemented in the scientific oncology community. Since then, the
      RECIST working group has identified several issues to examine further. Two key
      issues that required careful, data-based assessment were the maximum number of
      lesions that should be assessed at each evaluation and the added value of
      requiring confirmation of response. METHODS: To address these questions, data
      were obtained from 16 clinical trials in metastatic cancer, with patients
      enrolled between 1993 and 2005. A total of 6512 patients were included in the
      primary analysis dataset, accounting for over 18,000 potential target lesions.
      Nine percent of the included patients (n=585) had six or more reported target
      lesions. The response and progression outcomes in the database were calculated
      using an adjusted RECIST methodology with a maximum of 5 (or 3) target lesions
      with/without confirmation and this was compared to the original RECIST version
      1.0 which required up to 10 target lesions plus confirmation of response.
      RESULTS: Assessment of 5 lesions per patient led to a difference in best overall
      response assignment for an estimated 209 (3.2%) patients as compared to RECIST
      version 1.0. However, these changes did not affect the overall response rate.
      Progression-free survival was only minimally affected by measuring fewer lesions.
      In contrast, removing the requirement for response confirmation led to a
      significant increase in the numbers of patients classified as responders,
      resulting in a relative increase of approximately 19% in response rate. An
      algorithm using a maximum of three target lesions shows high concordance with the
      10 lesions requirement in terms of response and TTP assignment. Concern that
      appropriate assessment of disease within an organ requires two lesions to be
      followed per organ suggests the approach of following two target lesions per
      organ, up to a maximum of five target lesions overall. Both strategies seem
      reasonable based on the data warehouse. The requirement of response confirmation
      in trials where this is a primary end-point is recommended to be maintained as
      its removal would substantially increase reported response rates.

PMID- 19095438
TI  - Wine, liquor, beer and risk of breast cancer in a large population.
AB  - Population studies show a relation of alcohol drinking to an increased risk of
      breast cancer (BrCa). Aiming to investigate uncertainties about a risk threshold,
      the role of beverage type and interactions with other BrCa predictors, we
      performed a cohort study among 70,033 women, 2,829 of whom developed BrCa. Using
      Cox proportional hazards models with 8 covariates, the following relative risks
      (95% confidence intervals) for BrCa versus lifelong abstainers were found: 1.08
      (0.95-1.22) at <1 drink per day, 1.21 (1.05-1.40, p=0.01) at 1-2 drinks daily and
      1.38 (1.13-1.68, p=0.002) at > or = 3 drinks daily. Increased BrCa risk was
      concentrated in women with oestrogen receptor positive tumours with no major
      disparity related to choice of wine, liquor, beer or type of wine (red, white,
      etc). We conclude that with a threshold below 1-2 drinks daily, a hormone-related
      mechanism mediates a relation of alcohol drinking to an increased BrCa risk.

PMID- 19095439
TI  - A simulation study to evaluate the impact of the number of lesions measured on
      response assessment.
AB  - The objectives of this study were to evaluate whether the number of lesions that
      are used to measure tumour burden affects response assessment and inter-rater
      variability. In order to accomplish this, a simulation study was conducted. Data
      were generated from a mixed-effects mixture model. Parameter values to input in
      the model were obtained from the analysis of real data. Response assessments
      based on 10, five, three, two and one lesion were evaluated. There was little
      difference between response assessments based on five lesions and response
      assessments based on 10 lesions. When fewer than five lesions were used to assess
      response, there were notable differences from the 10 lesion-based response
      assessment. Basing response assessment on a small number of lesions tends to
      overestimate response rates and leads to misclassification of patients' response
      status. Therefore, measuring five lesions per patient appears to sufficiently
      capture patients' response to therapy. Measuring fewer than five lesions results
      in the loss of information that may adversely affect clinical trial results as
      well as patient management.

PMID- 19095440
TI  - The deacetylation reaction in Eucalyptus wood: kinetics and effects on the
      effective diffusion.
AB  - The removal of native acetyl groups from hardwood O-acetyl-glucuronoxylan has a
      strong effect on physical characteristics, accessibility and structure of this
      polymer. The removal also has effects on the swelling and ion transport capacity
      of the cell wall of hardwoods. In this work, a kinetic expression for Eucalyptus
      wood deacetylation is determined. Two liquid mediums are considered: a simple
      alkaline one and another with a higher sodium concentration. The kinetic
      expression is a power law for the acetyl content and the concentrations in the
      liquid medium dependence, and is an Arrhenius type expression for temperature
      dependence. The kinetic expression can be useful to predict the physical
      properties of wood since the analysis of deacetylation effects on effective
      capillarity (ECCSA) shows that the acetyl content is a determining factor of wood
      ionic transport capacity.

PMID- 19095441
TI  - Characterization of 5-aminolevulinate synthase from Agrobacterium radiobacter,
      screening new inhibitors for 5-aminolevulinate dehydratase from Escherichia coli
      and their potential use for high 5-aminolevulinate production.
AB  - The hemA gene encoding 5-aminolevulinate synthase (ALAS) from Agrobacterium
      radiobacter zju-0121 showed 92.6% homology with that from A. radiobacter ATCC4718
      and contained several rare codons. To enhance the expression of this gene,
      Escherichia coli Rosetta(DE3), which is a rare codon optimizer strain, was used
      as the host to construct an efficient recombinant strain. And the encoded protein
      was over-expressed as fusion protein and was purified by affinity purification on
      Ni-NTA agarose and by gel filtration chromatography on Sephadex G-25 Medium
      resin. The recombinant protein was partly characterized, and D-glucose, D
      fructose, D-xylose, D-mannose, L-arabinose, D-galactose, lactose, sucrose and
      maltose were detected to have no distinct inhibition on this recombinant ALAS.
      Meanwhile, 20mM D-glucose or D-xylose inhibited about 20% activity of ALA
      dehydratase (ALAD) from Escherichia coli Rosetta(DE3). Combining D-xylose as a
      new inhibitor for ALAD with D-glucose in fed-batch culture and based on the
      optimal culture system using Rosetta(DE3)/pET28a-hemA, the yield of ALA achieved
      was 7.3g/l (56 mM) under the appropriate conditions in the fermenter.

PMID- 19095442
TI  - Anthranilimide-based glycogen phosphorylase inhibitors for the treatment of type
      2 diabetes: 1. Identification of 1-amino-1-cycloalkyl carboxylic acid headgroups.
AB  - Optimization of the amino acid residue within a series of anthranilimide-based
      glycogen phosphorylase inhibitors is described. These studies culminated in the
      identification of anthranilimides 16 and 22 which displayed potent in vitro
      inhibition of GPa in addition to reduced inhibition of CYP2C9 and excellent
      pharmacokinetic properties.

PMID- 19095443
TI  - Anthranilimide-based glycogen phosphorylase inhibitors for the treatment of Type
      2 diabetes: 2. Optimization of serine and threonine ether amino acid residues.
AB  - Optimization of the amino acid residue of a series of anthranilimide-based
      glycogen phosphorylase inhibitors is described leading to the identification of
      serine and threonine ether analogs. t-Butylthreonine analog 20 displayed potent
      in vitro inhibition of GPa, low potential for P450 inhibition, and excellent
      pharmacokinetic properties.

PMID- 19095444
TI  - 1,2,3-Triazole derivatives as new cannabinoid CB1 receptor antagonists.
AB  - This letter reports the new entry of novel 1,2,3-triazole derivatives as CB1
      receptor antagonists. The design, synthesis and biological evaluation of N1 and
      N2 substituted 1,2,3-trizoles are described. The N2 substituted, symmetrical
      1,2,3-triazoles are more potent ligands than the unsymmetrical analogues. The in
      vitro activity of these triazoles is further improved by inserting a methylene
      group between the central core and the carbonyl side chain. The most potent
      antagonists prepared in this series (IC(50)<20 nM) are the triazoles containing
      benzyl amides. These triazoles also show excellent selectivity between CB1 and
      CB2 receptors (IC(50)>10 microM for CB2; CB2/CB1>1000).

PMID- 19095445
TI  - DNA gyrase (GyrB)/topoisomerase IV (ParE) inhibitors: synthesis and antibacterial
      activity.
AB  - The synthesis and antibacterial activities of three chemotypes of DNA
      supercoiling inhibitors based on imidazolo[1,2-a]pyridine and [1,2,4]triazolo[1,5
      a]pyridine scaffolds that target the ATPase subunits of DNA gyrase and
      topoisomerase IV (GyrB/ParE) is reported. The most potent scaffold was selected
      for optimization leading to a series with potent Gram-positive antibacterial
      activity and a low resistance frequency.

PMID- 19095446
TI  - Effect of incorporation of alkyl linkers into siRNAs on RNA interference.
AB  - Unintended (off-target) transcript silencing is a critical problem associated
      with RNA interference (RNAi)-based therapeutic applications. This paper shows
      that the incorporation of appropriate alkyl linkers at the center of the sense
      strands can suppress the off-target effects induced by the sense strands without
      reducing the RNAi-inducing activity of the antisense strands.

PMID- 19095447
TI  - Discovery and optimization of highly ligand-efficient oxytocin receptor
      antagonists using structure-based drug design.
AB  - A novel oxytocin antagonist was identified by 'scaffold-hopping' using Cresset
      FieldScreen molecular field similarity searching. A single cycle of optimization
      driven by an understanding of the key pharmacophoric elements required for
      activity led to the discovery of a potent, selective and highly ligand-efficient
      oxytocin receptor antagonist. Selectivity over vasopressin receptors was
      rationalized based on differences in the structure of the natural ligands.

PMID- 19095448
TI  - Replacing alkyl sulfonamide with aromatic sulfonamide in sulfonamide-type RXR
      agonists favors switch towards antagonist activity.
AB  - Retinoid X receptor (RXR) ligands are attractive candidates for clinical
      application because of their activity against tamoxifen-resistant breast cancer,
      taxol-resistant lung cancer, metabolic syndrome, and allergy. Though several RXR
      ligands, especially RXR antagonists, have been reported, the rational molecular
      design of such compounds is not well advanced. 4-[N-Methanesulfonyl-N-(5,5,8,8
      tetramethyl-5,6,7,8-tetrahydro-2-naphthyl)amino]nicotinic acid (5a) is a
      moderately RXRalpha-preferential agonist, and we examined the feasibility of
      replacing the methyl group on the sulfonamide with a longer alkyl chain or an
      aromatic ring as an approach to produce new RXR antagonists. Several of the
      resulting benzenesulfonanilide-type compounds showed RXR antagonist activity.
      This design strategy should be a useful approach for addressing the lack of
      structure diversity of RXR antagonists.

PMID- 19095449
TI  - Synthesis, in vitro antitrypanosomal and antibacterial activity of phenoxy,
      phenylthio or benzyloxy substituted quinolones.
AB  - Chagas' disease, caused by Trypanosoma cruzi(T. cruzi), is one of the most
      serious parasitic diseases in Latin America. The currently available
      chemotherapy, based on nifurtimox or benznidazole, is unsatisfactory due to the
      limited efficacy in the prevalent chronic stage of the disease and toxic side
      effects. In order to address these deficiencies, a series of quinolones based
      novel molecules have been synthesized and evaluated as potential antitrypanosomal
      agents. The most active analogue 10 inhibited T. cruzi with an IC(50) of 1.3
      microg/mL. The results of this study have implications in the development of
      novel quinolone's antitrypanosomal agents.

PMID- 19095450
TI  - HY251, a novel cell cycle inhibitor isolated from Aralia continentalis, induces
      G1 phase arrest via p53-dependent pathway in HeLa cells.
AB  - This study was aimed to elucidate the novel structure of HY251 isolated from the
      roots of Aralia continentalis and to evaluate its detailed inhibition mechanisms
      on cell cycle progression in HeLa cells. The structure of HY251 was elucidated
      based on the interpretation of the NMR spectra, as 3-propyl-2-vinyl
      1,2,3,3a,3b,6,7,7a,8,8a-decahydrocyclopenta[a]indene-3,3a,7a,8a-tetraol. The flow
      cytometric analysis revealed an appreciable G(1) phase arrest in HeLa cells
      treated with 100 microM of HY251. This HY251-induced G(1) phase arrest is
      associated with decreased expression of cyclin D3 and up-regulation of p21(CIP1)
      and p27(KIP1), via p53 phosphorylation at Ser-15 by transcriptional up-regulation
      of ATM, which resulted in increased hypophosphorylated pRb in HeLa cells.

PMID- 19095451
TI  - Novel NGF-potentiating diterpenoids from a Brazilian medicinal plant,
      Ptychopetalum olacoides.
AB  - From the MeOH extract of Ptychopetalum olacoides, which is used in Brazilian folk
      medicine for the treatment of chronic degenerative conditions of the nervous
      system, four novel clerodane-type diterpenoids named 6alpha,7alpha
      dihydroxyannonene (1), 7alpha,20-dihydroxyannonene (2), 7alpha
      hydroxysolidagolactone I (3), and ptycho-6alpha,7alpha-diol (4) were isolated by
      bioassay-directed fractionation using NGF-differentiated PC12 cells. The
      structures of 1-4 were established by extensive NMR spectroscopic analyses and
      chemical conversion. Compounds 1 and 2 significantly enhanced NGF-mediated
      neurite outgrowth in PC12 cells at concentrations ranging from 0.1 to 50.0 microM
      for 1 and 0.1 to 30.0 microM for 2, whereas 3 and 4 had no morphological effect
      on NGF-mediated PC12 cells in the same concentration range. The structure
      activity relationship of these compounds is also discussed.

PMID- 19095452
TI  - Forward lunge as a functional performance test in ACL deficient subjects: test
      retest reliability.
AB  - The forward lunge movement may be used as a functional performance test of
      anterior cruciate ligament (ACL) deficient and reconstructed subjects. The
      purposes were 1) to determine the test-retest reliability of a forward lunge in
      healthy subjects and 2) to determine the required numbers of repetitions
      necessary to yield satisfactory reliability. Nineteen healthy subjects performed
      four trials of a forward lunge on two different days. The movement time, impulses
      of the ground reaction forces (IFz, IFy), knee joint kinematics and dynamics
      during the forward lunge were calculated. The relative reliability was determined
      by calculation of Intraclass Correlation Coefficients (ICC). The IFz, IFy and the
      positive work of the knee extensors showed excellent reliability (ICC >0.75). All
      other variables demonstrated acceptable reliability (0.4>ICC<0.75). The relative
      reliability increased when more than a single forward lunge was used. In
      conclusion, the reliability was acceptable. It is recommended to represent the
      biomechanical variables as an average of at least three trials of the forward
      lunge.

PMID- 19095453
TI  - Superior pole sleeve fracture following patellar stabilisation.
AB  - Sleeve fractures of the superior pole of the patella are rare. The importance of
      their diagnosis lies in the fact that the avulsed fragment contains a source of
      bone forming tissue which may lead to duplication or enlargement of the patella.
      We report a case in a 16 year old boy who underwent plication of the medial
      patellofemoral ligament, vastus medialis obliquus advancement and percutaneous
      lateral release, for recurrent instability. Interruption of the blood supply with
      subsequent avascular necrosis is one possible mechanism for this complication.
      Another more likely mechanism is that of failure of the repair and re
      dislocation, which may have been contributed to by prolonged cast immobilization.

PMID- 19095454
TI  - Current perspective of TACE inhibitors: a review.
AB  - Rheumatoid Arthritis (RA) is one of the most common autoimmune inflammatory
      conditions, affecting approximately 1% of the adult population worldwide. TNF
      alpha is a pleitropic, pro-inflammatory cytokine which plays a pivotal role in
      the origin and progression of RA and other immune mediated disorders. The success
      of anti-TNF-alpha biological agents proved that inhibition of TNF-alpha could
      result in effective control of RA. Since the discovery of anti-TNF-alpha
      biologicals, much efforts have gone into developing an orally bioavailable small
      size TNF-alpha antagonist. One of the ways to block TNF-alpha in biological
      fluids is to inhibit TNF-alpha converting enzyme (TACE). This target has been
      validated in preclinical trials using TACE inhibitors. But, even after more than
      a decade no single TACE inhibitor has passed the Phase II clinical trials. Very
      recently, it has been shown that TACE inhibitors could also be used for
      inhibition of pathogenic EGFR signaling in cancer. Hence, TACE inhibitors could
      perform a dual role, in curing not only RA but also certain cancerous conditions.
      Developments in the field have prompted us to review the research work on TACE
      inhibitors, especially their structure activity relationships and molecular
      modeling studies.

PMID- 19095455
TI  - Organocatalyzed highly atom economic one pot synthesis of tetrahydropyridines as
      antimalarials.
AB  - A highly atom economic one pot synthesis of tetrahydropyridines was achieved by L
      proline/TFA catalysed multicomponent reaction of beta-keto-esters, aromatic
      aldehydes and anilines. The synthesized compounds were screened against
      Plasmodium falciparum in vitro and one of them showed antimalarial activity with
      MIC as low as 0.09 microg/mL.

PMID- 19095456
TI  - Interrogating the mechanism of a tight binding inhibitor of AIR carboxylase.
AB  - The enzyme aminoimidazole ribonucleotide (AIR) carboxylase catalyzes the
      synthesis of the purine intermediate, 4-carboxy-5-aminoimidazole ribonucleotide
      (CAIR). Previously, we have shown that the compound 4-nitro-5-aminoimidazole
      ribonucleotide (NAIR) is a slow, tight binding inhibitor of the enzyme with a Ki
      of 0.34 nM. The structural attributes and the slow, tight binding characteristics
      of NAIR implicated this compound as a transition state or reactive intermediate
      analog. However, it is unclear what molecular features of NAIR contribute to the
      mimetic properties for either of the two proposed mechanisms of AIR carboxylase.
      In order to gain additional information regarding the mechanism for the potent
      inhibition of AIR carboxylase by NAIR, a series of heterocyclic analogs were
      prepared and evaluated. We find that all compounds are weaker inhibitors than
      NAIR and that CAIR analogs are not alternative substrates for the enzyme.
      Surprisingly, rather subtle changes in the structure of NAIR can lead to profound
      changes in binding affinity. Computational investigations of enzyme intermediates
      and these inhibitors reveal that NAIR displays an electrostatic potential surface
      similar to a proposed reaction intermediate. The result indicates that AIR
      carboxylase is likely sensitive to the electrostatic surface of reaction
      intermediates and thus compounds which mimic these surfaces should possess tight
      binding characteristics. Given the evolutionary relationship between AIR
      carboxylase and N(5)-CAIR mutase, we believe that this concept extends to the
      mutase enzyme as well. The implications of this hypothesis for the design of
      selective inhibitors of the N(5)-CAIR mutase are discussed.

PMID- 19095457
TI  - A simulation study of the DQE of a linear plastic scintillating fiber array for
      hard gamma-rays.
AB  - The detector quantum efficiency (DQE) of a linear plastic scintillating fiber
      (PSF) array coupled with a charge-coupled device (CCD) for hard gamma-ray imaging
      is studied using a Monte Carlo simulation. The focus is on the energy from a few
      MeV to about 12 MeV. The excellent characteristic of PSF offers a method to
      balance the detection efficiency and spatial resolution. Our simulation results
      indicate that the modulation transfer function (MTF) for different energies
      become almost the same below the certain frequency and the DQE should be better
      at lower frequency for imaging lower incident energy. These characteristics
      suggest that the PSF may be useful for detecting high energy gamma-rays.

PMID- 19095458
TI  - Extended replacement of aortic arch aneurysms through left posterolateral
      thoracotomy.
AB  - OBJECTIVE: To present our experience of total aortic arch replacement through a
      left posterolateral thoracotomy. METHODS: Sixteen patients (13 males; mean age
      62.1+/-11.3 years) with extended thoracic aortic aneurysms, including those in
      the thoracoabdominal aorta, underwent replacement through a left posterolateral
      thoracotomy. The pathology of the diseased aorta was non-dissecting aneurysm due
      to aortitis in 1 patient and aortic dissection in 15 patients (acute type A: 1,
      chronic type A: 12, chronic type B: 2). In a prior operation, the patient with
      aortitis had undergone the Bentall procedure with endovascular stenting of the
      brachiocephalic artery, and among the other 15 patients, one previously had
      endovascular stenting for the aortic arch and 12 had hemi-arch replacement for
      acute type A dissection. Extension of arch replacement was the aortic arch and
      descending aorta in eight patients, the ascending arch and descending aorta in
      five patients and the descending arch, and thoracoabdominal aorta in three
      patients. Additional retroperitoneal dissection was required for the repair of a
      thoracoabdominal aortic aneurysm. RESULTS: One patient died of traumatic cerebral
      hemorrhage on day 145 (hospital mortality 6.3%). Average duration of ventilation
      support was 19.4+/-17.0h and length of ICU stay was 3.6+/-1.6 days. Actuarial
      survival at 2 years after the operations was 67.7%. However, no aortic-related
      mortality was observed during follow-up. CONCLUSIONS: Early results of extended
      aortic arch replacement through a left posterolateral thoracotomy were
      satisfactory in selected patients.

PMID- 19095459
TI  - Study on continuous (254 nm) and pulsed UV (266 and 355 nm) lights on BVD virus
      inactivation and its effects on biological properties of fetal bovine serum.
AB  - Both continuous UV lights and pulsed UV lasers have potentials to inactivate
      known and emerging viruses. Bovine viral diarrhea virus (BVDV), from the
      Pestivirus genus, is known to be a common viral contamination in (fetal) bovine
      serum (FBS). Also, BVDV has been used in the blood product industry as a
      surrogate for Hepatitis C virus (HCV), due to its similarity in structure and
      genome. Germicidal UV lamp with the wavelength of 254 nm and Nd:YAG laser (pulsed
      UV laser) in its third and fourth harmonic with the wavelengths of 355 and 266
      nm, respectively, were used. BVDV suspended in PBS or FBS were exposed to
      different intensities and doses and then reduction in BVDV titer were calculated.
      To complete inactivation of BVDV suspended in PBS and PBS containing 5% FBS, 1.6
      (t=30 min) and 3.2 (t=60 min)J/cm(2) were used. The minimum doses for
      inactivation of BVDV suspended in PBS with the 355 and 266 nm of pulsed UV laser
      were 352 and 92.25 J/cm(2). Also, the minimum doses for inactivation of BVDV
      suspended in FBS with 355 and 266 nm wavelengths of pulsed UV laser were 704 and
      127 J/cm(2). To evaluate the irradiated FBS quality to support cell culture
      growth, FBS was treated with the dose of 190.5 J/cm(2) and 266 nm pulsed UV laser
      and was used to grow Vero cells, in comparison with a control group. The
      viability of cells in two groups was identical and the statistical evaluation
      showed no significant difference in 12 passages.

PMID- 19095460
TI  - Early-life origins of metabolic dysfunction: role of the adipocyte.
AB  - More than 60% of adults in the US are classified as overweight, with most
      developing associated metabolic problems. It is increasingly clear that the
      origins of obesity and metabolic disease are early in life, yet the physiological
      basis for this is not well understood. We propose that perturbations to nutrient
      supply in utero affect adipocyte development, altering functional properties and
      promoting excess body fat accumulation after birth. We also propose that
      excessive body fat accumulation leads to leptin and insulin resistance in these
      individuals, rendering them more susceptible to further weight gain and metabolic
      deterioration. Finally, we propose that interventions that inhibit this early
      increase in fat deposition have the potential to interrupt the pathway to
      obesity.

PMID- 19095461
TI  - Fast reversed-phase liquid chromatography to reduce back exchange and increase
      throughput in H/D exchange monitored by FT-ICR mass spectrometry.
AB  - In solution-phase hydrogen/deuterium exchange (HDX), it is essential to minimize
      the back-exchange level of H for D after the exchange has been quenched, to
      accurately assign protein conformation and protein-protein or protein-ligand
      interactions. Reversed-phase HPLC is conducted at low pH and low temperature to
      desalt and separate proteolytic fragments. However, back exchange averages
      roughly 30% because of the long exposure to H(2)O in the mobile phase. In this
      report, we first show that there is no significant backbone amide hydrogen back
      exchange during quench and digestion; backbone exchange occurs primarily during
      subsequent liquid chromatography separation. We then show that a rapid reversed
      phase separation reduces back exchange for HDX by at least 25%, resulting from
      the dramatically reduced retention time of the peptide fragments on the column.
      The influence of retention time on back exchange was also evaluated. The rapid
      separation coupled with high-resolution FT-ICR MS at 14.5 T provides high amino
      acid sequence coverage, high sample throughput, and high reproducibility and
      reliability.

PMID- 19095462
TI  - Neer Award 2007: Reversion of structural muscle changes caused by chronic rotator
      cuff tears using continuous musculotendinous traction. An experimental study in
      sheep.
AB  - HYPOTHESIS: Chronic rotator cuff tears are associated with irreversible
      architectural muscle changes and a high rate of repair failure. The changes
      observed in man and their irreversibility with a single stage repair can be
      reproduced in sheep. It was the purpose of this experiment to test the hypothesis
      that slow, continuous elongation of a retracted musculotendinous unit allows
      reversal of the currently irreversible structural muscle changes. MATERIALS AND
      METHODS: The infraspinatus tendon of 12 sheep was released using a greater
      tuberosity osteotomy and allowed to retract for 4 months. Then, a new device was
      mounted on the scapular spine and used to extend the infraspinatus
      muscuculotendinous unit transcutaneously by 1 mm per day. Thereafter, the tendon
      was repaired back to the greater tuberosity. We assessed the muscular
      architecture using magnetic resonance imaging, macroscopic dissection, histology,
      and electron microscopy. Fatty infiltration (in Hounsfield units 1/4 HU) and
      muscular cross-sectional area (in % of the control side) were monitored with
      computed tomography at tendon release, initiation of elongation, repair, and at
      sacrifice. RESULTS: Sixteen weeks after tendon release, the mean tendon
      retraction was 29 +/- 6 mm (14% of original length, P = .008). In 8 sheep,
      elongation was achieved as planned (group I), but in 4, the elongation failed
      technically (group II). The mean traction time was 24 +/- 6 days with a mean
      traction distance of 19 +/- 4 mm. At sacrifice, the mean pennation angle in the
      infraspinatus of group I was not different from the control side (29.8 degrees +/
      7.5 degrees vs. 30 degrees +/-6 degrees , P = .575). In group II, the pennation
      angle had increased from 30 degrees +/-6 degrees to 55 degrees +/-14 degrees (P =
      .035). There was no fatty infiltration at the time of tendon release. After
      retraction, there was a significant increase in fatty infiltration of the
      infraspinatus muscle and a decrease of its cross-sectional area to 57% of the
      contralateral side (P = .0001). During traction, the degree of fatty infiltration
      remained unchanged (36 HU to 38 HU, P = .381), and atrophy improved to a muscle
      square area of 78% of the contralateral side (P = .0001) in group I. In group II,
      an increase of fatty infiltration was measured from 36 HU to 28 HU; however, this
      increase was not significant (P = .144). Atrophy did not change in group II (57
      55%, P = .946). At sacrifice, the remaining muscle mass was 64% in group I and
      46% in group II (P = .019). DISCUSSION: Our preliminary results document, that
      continuous elongation of a retracted, fatty infiltrated and atrophied
      musculotendinous unit is technically feasible. CONCLUSION: In the sheep,
      continuous elongation can lead to restoration of normal muscle architecture, to
      partial reversal of muscle atrophy, and to arrest of the progression of fatty
      infiltration. LEVEL OF EVIDENCE: Basic science level 2; Prospective comparative
      therapeutic study.

PMID- 19095463
TI  - Selective capsular repair for the treatment of anterior-inferior shoulder
      instability: review of seventy-nine shoulders with seven years' average follow
      up.
AB  - HYPOTHESIS: Selective capsular repair for the treatment of antero-inferior
      shoulder instability gives satisfactory results at mid-range follow-up. MATERIALS
      AND METHODS: Seventy-five patients (79 shoulders) with anterior instability
      underwent selective tightening of the anterior capsule and repair of any labral
      lesion. RESULTS: At an average of seven years (5-12 years), results according to
      the Duplay-Walch score and Rowe score were satisfactory in 80% and 92% of the
      cases, respectively. Most patients (84%) were able to return to their previous
      sports activity at the same level, and 90% were satisfied with their surgery.
      Recurrence of instability was observed in 10 patients (12.6%). Restriction of
      motion was limited to external rotation and averaged a loss of 12.6 degrees elbow
      at the side, and 6 degrees at 90 degrees of abduction. Dynamometric evaluation
      found slight decrease in strength in internal rotation in 32 shoulders. According
      to the Samilson and Prieto classification, signs of osteoarthritis were present
      in 52% of the cases. Older age at the first episode of instability was the only
      factor correlated with development of postoperative osteoarthritis. DISCUSSION:
      This study supports the results of other studies that anatomic stabilization of
      the shoulder demonstrates high levels of recovery of shoulder stability
      (recurrence rates 12.6%), with minimum restriction of range-of-motion, but with a
      relatively high incidence of possible development of osteoarthritis. CONCLUSION:
      This retrospective study from a single center revealed that selective capsular
      repair for the treatment of posttraumatic anterior glenohumeral instability
      yielded a 90% of satisfaction rate and 80% excellent and good functional results.
      LEVEL OF EVIDENCE: Level 4; Retrospective case series, no control group.

PMID- 19095464
TI  - Impingement syndrome: temporal outcomes of nonoperative treatment.
AB  - HYPOTHESIS: We prospectively studied patients with impingement syndrome to look
      at outcomes of nonoperative treatment on a temporal basis. MATERIALS AND METHODS:
      Temporal outcomes of 100 consecutive patients treated for impingement syndrome
      were prospectively evaluated. All patients began a standardized, nonoperative
      treatment protocol consisting of a subacromial steroid injection, followed by
      physical therapy. RESULTS: Data were available on 94 patients at the final two
      year follow-up assessment. Overall, 74 of 94 patients did not require surgery. In
      that group, the average American Shoulder and Elbow Surgeons (ASES) outcome score
      increased from 56 to 95, with an average decrease in the pain score from 4.8 to
      0.6. Improvement was demonstrated in patient shoulder outcome scores (ASES score)
      and visual analog pain scores between treatment initiation and the one-year
      follow-up assessment (p < .0001); no improvement was identified past one year. Of
      the non-surgical patients, 22 continued to have some shoulder pain. CONCLUSION:
      Of patients with impingement syndrome treated nonoperatively, 79% did not require
      surgery after two-year follow-up. Predictors of patients going on to surgical
      intervention included the total number of subacromial steroid/lidocaine
      injections and patient response to the initial subacromial injection. Of the
      patients not undergoing surgery, 30% continued to have some shoulder pain. LEVEL
      OF EVIDENCE: Level 1; Prospective prognosis study, >80% follow-up.

PMID- 19095465
TI  - Revision total shoulder arthroplasty for painful humeral head replacement with
      glenoid arthrosis.
AB  - HYPOTHESIS: After humeral head replacement, revision total shoulder arthroplasty
      may become necessary for painful glenoid arthrosis. The hypothesis of this study
      was revision surgery would significantly relieve the patients' pain. MATERIALS
      AND METHODS: This report retrospectively reviewed the results of revision total
      shoulder arthroplasty in seventeen patients with a painful humeral head
      replacement and glenoid arthrosis. The mean time interval to revision was 36.4
      months (6-144) and the patients were followed for an average of 56.1 months (24
      119). Outcomes were graded with the Neer classification. RESULTS: There were 7
      (41.2%) excellent, 5 (29.4%) satisfactory, and 5 (29.4%) unsatisfactory results.
      The visual analogue pain score decreased from 8.8 to 2.4, flexion improved from
      73 degrees to 124, abduction from 63 to 115.6, and external rotation from 12.1 to
      46.8. In 13 shoulders with sufficient data, the ASES score was 76.8 and the SST
      9.5. It was necessary to revise the humeral stem in 12 of the 17 procedures,
      typically for poor stem position or improved exposure. CONCLUSION: Conversion of
      humeral head replacement to total shoulder arthroplasty can be accomplished with
      excellent results, but the surgery is complex and unsatisfactory results are
      frequent. LEVEL OF EVIDENCE: Level 4; Retrospective case series, no control
      group.

PMID- 19095467
TI  - An anatomic and histologic study of the coracohumeral ligament.
AB  - Although the anatomy and histology of the coracohumeral ligament (CHL) play an
      important role in the diagnosis and treatment of frozen shoulder, they remain
      unclear. Our objective was to study the anatomic features of the CHL and analyze
      its histology. Twenty-six fresh-frozen, normal cadaveric shoulders were used to
      examine the position and morphology of the CHL and their relationship with the
      superior glenohumeral ligament and to determine the CHL's histologic features in
      comparison with the joint capsule and coracoacromial ligament. The CHLs were all
      located in the rotator interval, with an irregular trapezoidal structure. The
      subacromial bursa was above the CHL, and the subcoracoid bursa was below the it.
      The CHLs in all shoulders originated from the lateral aspect of the base of the
      coracoid process. In 11 shoulders, it inserted into the supraspinatus tendon,
      whereas in 11 other shoulders, it inserted into the rotator interval. In 3
      shoulders, the CHLs were split and inserted into both the supraspinatus and
      subscapularis tendons, respectively. Finally, the CHL in 1 shoulder only inserted
      into the subscapularis tendon. We also observed that the pectoralis minor tendons
      in 4 shoulders passed over the coracoid process top and inserted into the CHLs.
      In 11 shoulders, a complex of the CHL and the superior glenohumeral ligament was
      formed. Histologically, the CHL was found to be similar to the joint capsule
      without any ligament features. The position, morphology, and origin of the CHL
      did not change much, but its insertion varied greatly. In addition, the CHL had
      the histologic feature of a capsule, not a ligament.

PMID- 19095466
TI  - Extracorporeally irradiated scapula as autograft in tumor surgery.

PMID- 19095468
TI  - Subscapularis repair after shoulder arthroplasty: biomechanical and clinical
      validation of a novel technique.
AB  - HYPOTHESIS: We hypothesized that releasing the subscapularis with lesser
      tuberosity bone may improve strength of fixation of the subscapularis during
      total shoulder atthroplasty (TSA). MATERIALS AND METHODS: In 15 cadaveric humeri,
      all musculature was removed except the subscapularis. A standard humeral head
      osteotomy was performed for TSA. The subscapularis was released with a fleck of
      lesser tuberosity bone in 10 specimens from five matched pairs, and a tenotomy
      was performed in five. Five osteotomies were repaired with single-row heavy non
      absorbable sutures and five with an additional double-row. Repairs were subjected
      to cyclical loading at 180 newtons for 400 cycles, increasing by 180 newtons to
      failure. A retrospective review of 100 consecutive patients who underwent dual
      row repair of the subscapularis fleck osteotomy following TSA was also performed
      with minimal follow-up of 24 months (24-48). RESULTS: Both single (430 N) and
      double-row (466 N) fixation of the fleck osteotomy were significantly stronger
      than tenotomy suture repair (252 N) (p < .04). There was no significant
      difference between single and double-row ultimate strengths. Qualitatively,
      double-row fixation fixed the fleck osteotomy more securely to the donor site
      with respect to gross rotational motion. At final clinical review, the lift-off
      test was rated as normal in 79%. The belly press was rated as normal in 86%.
      Eighty-two percent were able to tuck in their shirts. CONCLUSION: Subscapularis
      release with fleck osteotomy provides superior biomechanical ultimate strength
      compared to standard tenotomy. There was no visible motion during biomechanical
      testing with dual-row osteotomy fixation compared to single-row fixation.
      Clinical results of this dual-row technique document showed good restoration of
      subscapularis integrity for activities of daily living. LEVEL OF EVIDENCE: Basic
      science study and level 4; retrospective review, case series, no control group.

PMID- 19095469
TI  - Posterior bony humeral avulsion of glenohumeral ligament with reverse bony
      Bankart lesion.

PMID- 19095470
TI  - Symptoms of the knee and hip in individuals with and without limb length
      inequality.
AB  - OBJECTIVE: This cross-sectional study examined the association of limb length
      inequality (LLI) with chronic joint symptoms at the hip and knee in a large,
      community-based sample, adjusting for the presence of radiographic osteoarthritis
      (OA) and other confounders. METHODS: The total study group comprised 3012
      participants with complete knee symptoms data, 3007 participants with complete
      hip symptoms data, and 206 with LLI>or=2 cm. Presence of chronic knee symptoms
      was defined as report of pain, aching, or stiffness (symptoms) of the knee on
      most days. Presence of chronic hip symptoms was defined as hip pain, aching, or
      stiffness on most days or groin pain. Multiple logistic regression models were
      used to examine the relationship of LLI with knee and hip symptoms, while
      adjusting for demographic and clinical factors, radiographic knee or hip OA and
      history of knee or hip problems (joint injury, fracture, surgery, or congenital
      anomalies). RESULTS: Participants with LLI were more likely than those without
      LLI to have knee symptoms (56.8% vs 43.0%, P<0.001), and hip symptoms (49.5% vs
      40.0%, P=0.09). In adjusted models, knee symptoms were significantly associated
      with presence of LLI (adjusted odds ratio [aOR]=1.41, 95% confidence interval,
      [95% CI] 1.02-1.97), but the relationship between hip symptoms and LLI (aOR=1.20,
      95% CI 0.87-1.67) was not statistically significant. CONCLUSION: LLI was
      moderately associated with chronic knee symptoms and less strongly associated
      with hip symptoms. LLI may be a new modifiable risk factor for therapy of people
      with knee or hip symptoms.

PMID- 19095471
TI  - Western blot quantification of aggrecan fragments in human synovial fluid
      indicates differences in fragment patterns between joint diseases.
AB  - OBJECTIVE: To develop a Western blot method for quantification of multiple
      aggrecan fragments in human synovial fluids (SFs). METHOD: SF aggrecan fragments
      were prepared from knee healthy (reference), knee injury and arthritis subjects
      by CsCl gradient centrifugations collecting D1 fractions. Samples were analyzed
      by Western blot, using antibodies against the N-terminal epitope ARGS and the G3
      domain, and fragments were quantified using a digital luminescence image
      analyzer. RESULTS: The method had a coefficients of variation of 10-30%, and a
      high correlation (r(S)=0.86) with a corresponding enzyme-linked immunosorbent
      assay (ELISA). The SFs from reference, knee injured and arthritic subjects
      contained two major ARGS fragments, ARGS-SELE and ARGS-CS1, and three major G3
      fragments (GRGT-G3, GLGS-G3 and AGEG-G3). Compared to the reference, the acute
      arthritis and acute joint injury groups had a 30-fold elevated concentration of
      ARGS fragments, and both groups had a higher proportion of the aggrecan in joint
      fluid as ARGS fragments compared to the other groups. The reference and chronic
      injury groups had an excess of ARGS-CS1 fragments over ARGS-SELE fragments, while
      subjects with acute arthritis or osteoarthritis had a more even distribution
      between these fragments. CONCLUSIONS: We have developed a novel Western blot
      quantification method for quantification of SF aggrecan fragments which can
      differentiate fragments of different sizes sharing the same epitope. The anti
      ARGS and anti-G3 quantitative Western blots provided information important for a
      better understanding of the proteolytic pathways in aggrecan breakdown,
      information that discriminates between different joint diseases, and may aid in
      identification of new biomarkers.

PMID- 19095472
TI  - Resistin is elevated following traumatic joint injury and causes matrix
      degradation and release of inflammatory cytokines from articular cartilage in
      vitro.
AB  - OBJECTIVE: Resistin is a secreted factor that is elevated in rheumatoid arthritis
      (RA) and believed to drive joint inflammation in vivo. This study was undertaken
      to determine if resistin is present in the joint following joint injury and to
      elucidate the role of resistin in cartilage degradation. METHODS: The level of
      resistin was measured in paired synovial fluid (SF) and serum samples from
      patients following joint injury (anterior cruciate ligament, ACL or meniscus
      tear). Localization of resistin was visualized by immunohistochemistry of
      synovial tissue and cartilage from healthy and OA donors. Mouse and human
      cartilage cultures were used to assess the effect of resistin on cartilage
      metabolism. RESULTS: In trauma patients, resistin levels declined with increasing
      time post injury. The resistin levels were highest in samples collected up to 1
      week following traumatic injury (SF: 2980 pg/ml, serum: 7901 pg/ml) and lowest in
      samples collected 6-26 years post injury (SF: 686 pg/ml, serum: 5682 pg/ml).
      Resistin was shown to be expressed in macrophage-like cells in both healthy and
      OA synovial tissue. Treatment of mouse cartilage cultures with recombinant
      resistin led to a dose dependent loss of proteoglycan and induction of
      inflammatory cytokine and PGE(2) production. Recombinant resistin inhibited
      proteoglycan synthesis in human cartilage explants. CONCLUSION: Resistin is
      elevated both systemically and locally in the weeks immediately following joint
      injury and has a direct effect on cartilage matrix turnover and cytokine
      production. Resistin may play a role in the early stages of trauma-induced OA and
      may represent a new therapeutic target to slow joint destruction in OA.

PMID- 19095473
TI  - A comparative study of two noninvasive techniques to evaluate implant stability:
      Periotest and Osstell Mentor.
AB  - OBJECTIVES: The purpose of this study was to examine the usefulness of Periotest
      and Osstell Mentor (a resonance frequency analysis) as nondestructive analytical
      tools for determining implant stability in clinics, to evaluate the precision of
      both instruments, and to determine the applicability of these measured values as
      clinically relevant indices. STUDY DESIGN: Four adult mongrel dogs weighing about
      12 to 15 kg were used in this study. Bilateral extractions of the first through
      the fourth mandibular and maxillary premolars were performed and a total of 48
      commercially pure titanium screw implants (USII Plus; OSTEM Implant, Seoul,
      Republic of Korea) were placed at 4 weeks after extraction. All implants (10 mm
      length and 3.3 mm diameter) were self-tapping and surface-treated with resorbable
      blast media (RBM). Periotest values (PTVs) obtained from Periotest, and Implant
      Stability Quotient (ISQ) obtained from Osstell Mentor, were measured at the time
      of implantation, and 3 and 6 weeks after implantation. At 3 and 6 weeks after
      implantation, 4 dogs were humanely killed and histomorphometric analysis was
      performed. The new peri-implant bone formation rate (NBFR) was measured. RESULTS:
      The PTV value was lower and ISQ value was higher at 6 weeks when compared with
      data collected at 3 weeks after implantation. The PTVs of the maxilla were higher
      than the mandible and the ISQ values of the maxilla were lower than the mandible.
      Based on the NBFR, the 6-week group showed higher bone formation when compared to
      the 3-week group, correlating to the observed PTV and ISQ values. Additionally,
      the NBFR was higher in the maxilla than the mandible. No significant difference
      between PTV and ISQ was also observed when PTV and ISQ were compared to NBFR.
      CONCLUSION: The results indicated that the Periotest and Osstell Mentor, both
      noninvasive diagnostic devices, were useful and comparably reliable, showing a
      strong association with each other in assessing implant stability.

PMID- 19095474
TI  - Melatonin, sleep disturbance and cancer risk.
AB  - The pineal hormone melatonin is involved in the circadian regulation and
      facilitation of sleep, the inhibition of cancer development and growth, and the
      enhancement of immune function. Individuals, such as night shift workers, who are
      exposed to light at night on a regular basis experience biological rhythm (i.e.,
      circadian) disruption including circadian phase shifts, nocturnal melatonin
      suppression, and sleep disturbances. Additionally, these individuals are not only
      immune suppressed, but they are also at an increased risk of developing a number
      of different types of cancer. There is a reciprocal interaction and regulation
      between sleep and the immune system quite independent of melatonin. Sleep
      disturbances can lead to immune suppression and a shift to the predominance in
      cancer-stimulatory cytokines. Some studies suggest that a shortened duration of
      nocturnal sleep is associated with a higher risk of breast cancer development.
      The relative individual contributions of sleep disturbance, circadian disruption
      due to light at night exposure, and related impairments of melatonin production
      and immune function to the initiation and promotion of cancer in high-risk
      individuals such as night shift workers are unknown. The mutual reinforcement of
      interacting circadian rhythms of melatonin production, the sleep/wake cycle and
      immune function may indicate a new role for undisturbed, high quality sleep, and
      perhaps even more importantly, uninterrupted darkness, as a previously
      unappreciated endogenous mechanism of cancer prevention.

PMID- 19095475
TI  - Role of spinal microglia in myositis-induced central sensitisation: an
      immunohistochemical and behavioural study in rats.
AB  - There is increasing evidence that spinal glial cells play an important role in
      chronic pain states. However, so far no data on the role of microglia in muscle
      pain are available. The aim of the present study was to investigate the
      involvement of spinal microglial cells in chronic muscle pain. In a rat model of
      chronic muscle inflammation (injection of complete Freund s adjuvant into the
      gastrocnemius-soleus muscle) alterations of microglia were visualized with
      quantitative OX-42 immunohistochemistry in the dorsal horn of the segments L4 and
      L5 12 days after induction of inflammation. In behavioural experiments the
      influence of chronic intrathecally applied minocycline - a specific microglia
      inhibitor - or an antibody against tumour necrosis factor-alpha (TNF-alpha; a
      cytokine released from microglia) on pain-related behaviour was investigated
      after 1, 3, 6, and 12 days. The immunhistochemical data show that in the deep
      laminae of the spinal dorsal horn microglial cells reacted with morphological
      changes to the muscle inflammation. Following inflammation, the mean boundary
      length surrounding the OX-42 immunostained area was significantly shorter. This
      indicates that microglial cells were activated by the myositis and withdrew their
      processes. Chronic intrathecal administration of minocycline or anti TNF-alpha
      with an osmotic mini-pump largely normalised the inflammation-induced changes in
      spontaneous exploratory behaviour and attenuated the hypersensitivity to
      mechanical stimulation. Both the immunohistochemical and behavioural data show
      that spinal microglial cells are involved in nociceptive processes in the cause
      of a chronic muscle inflammation.

PMID- 19095476
TI  - Introduction of low dose transdermal buprenorphine -- did it influence use of
      potentially addictive drugs in chronic non-malignant pain patients?
AB  - The aim was to study the introduction of the new low dose transdermal
      buprenorphine (LD-TD-BUP) in Norway, particularly with regard to former use and
      co-medication with other potentially addictive drugs. The nationwide Norwegian
      Prescription Database contains information on all prescription drugs dispensed to
      individual non-institutionalised patients, and we may follow all individuals who
      received LD-TD-BUP (Norspan) after marketing on the Norwegian market on 15/11/05.
      We studied all prescriptions of opioids and other potentially addictive drugs to
      patients receiving at least two LD-TD-BUP prescriptions during 2004-2006. Poisson
      regressions were run with concomitant use of addictive drugs (yes, no) as the
      endpoint. Overall, 1884, non cancer individuals received at least two
      prescription of LD-TD-BUP. Of these 91.7% received prescriptions of other opioids
      and 58.6% of them had also been prescribed benzodiazepines/carisoprodol before
      the prescription of LD-TD-BUP. Of the LD-TD-BUP users who received more than one
      prescription, 60% co-medicated with at least one other potentially addictive
      drug, and 24% with at least two. In the multivariate analysis, the variables
      associated with a higher likelihood of using co-medicated drugs were: previous
      use of benzodiazepines/carisoprodol relative risk RR=16.7 (95% CI 10.4-26.9),
      previous use of opioids RR=4.0 (1.9-8.7) and younger age 20-40 years RR=1.9 (1.6
      2.3). So far, it is questionable whether the introduction of LD-TD-BUP actually
      has stabilised opioids consumption or whether it has complicated and increased
      the consumption of potentially addictive drugs.

PMID- 19095477
TI  - A dynamics study of the A-chain of ricin by terahertz vibrational calculation and
      normal modes analysis.
AB  - We studied the terahertz (THz) spectroscopy and low frequency normal modes of
      both apo- and holo- (adenosine monophosphate (AMP)-bound) ricin-A-chain (RTA) as
      a means to understand the dynamical changes that RTA undergoes upon substrate
      binding. The calculated THz spectra of apo- and holo-RTAs demonstrated a general
      intensity suppression upon substrate binding, which is attributed to the reduced
      number of collective motion in THz region. In normal mode analysis of RTA we find
      a shearing motion that is shared by both the apo- and holo-RTAs, whereas a
      breathing motion, and an upward hinge rising and an alpha-G bending
      characteristic motion are dampened significantly upon AMP binding, suggesting
      these motions are involved in the necessary flexibility of the active site. In
      contrast, we find a normal mode motion that separates domains I and II of RTA at
      the interface that is more common in the holo-protein. We hypothesized that the
      flexibility of the entrance of RTA can facilitate the entry of rRNA and allow the
      substrate to adjust its conformation and orientation prior to depurination. This
      process suggests an rRNA binding pathway which is supplemental the current RTA
      depurination mechanism.

PMID- 19095478
TI  - Chronic kidney disease with three cases of oxalate-like nephrosis in Ragdoll
      cats.
AB  - Two unrelated Ragdoll cat mothers in Norway were found dead from renal disease.
      The histopathology was consistent with oxalate nephrosis with chronic or acute-on
      chronic underlying kidney disease. Both cats had offspring and relatives with
      signs of urinary tract disease, including a kitten dead with urethral gravel.
      Eleven living Ragdoll cats, including nine relatives of the dead cats and the
      male father of a litter with similarly affected animals, were tested for primary
      hyperoxaluria (PH) type 1 and 2 by urine oxalate and liver enzyme analysis. Renal
      ultrasound revealed abnormalities in five living cats. One of these was azotaemic
      at the time of examination and developed terminal kidney disease 9 months later.
      A diagnosis of PH was excluded in 11 cats tested. The inheritance and
      aetiological background of the renal disease present in the breed remains
      unresolved at this point in time.

PMID- 19095480
TI  - Cutaneous leishmaniasis in Sri Lanka: a study of possible animal reservoirs.
AB  - BACKGROUND: Cutaneous leishmaniasis (CL) has been detected with increasing
      frequency in Sri Lanka in recent years. Leishmania donovani has been identified
      as the causative agent, but no information is available on vector(s) or
      reservoir(s). In this paper we present data on the screening of possible
      reservoirs for evidence of infection. METHODS: Patients with clinically
      suggestive CL referred from dermatology clinics for a confirmatory diagnosis were
      examined parasitologically and by PCR. There were no immunocompromised patients
      and none had any visceralizing symptoms. Pet dogs and rodents from areas where
      the patients were diagnosed were similarly examined for infection. RESULTS: The
      disease was confirmed in 86 of 116 patients. All positive patients were from
      rural areas of the country, closely associated with scrub jungles. Of the 151
      dogs examined, two showed Leishmania amastigotes in Giemsa-stained smears, one in
      the skin and one in peripheral blood. None of the 47 rodents screened showed any
      evidence of Leishmania infection. CONCLUSIONS: The evidence gathered shows that
      in Sri Lanka the disease is restricted to persons in the hinterland areas, with a
      possibility of it being a zoonosis. The detection of Leishmania amastigotes in
      two dogs is, however, not sufficient to incriminate them as reservoirs. More
      studies are needed for evidence of reservoir(s) and identification of behavior of
      the vector species in order to explain the atypical presentation of L. donovani
      in Sri Lanka.

PMID- 19095479
TI  - Gastrointestinal tract pseudo-obstruction or obstruction due to Mycobacterium
      tuberculosis breakthrough.
AB  - The development of tuberculosis-related bowel obstruction or pseudo-obstruction
      during anti-tuberculosis therapy is rarely reported in immunocompetent patients.
      A 44-year-old male, who had neither HIV infection nor diabetes, was hospitalized
      because of pulmonary tuberculosis in November 2006. Three months after starting
      anti-tuberculosis therapy, he was admitted for suspected mechanical bowel
      obstruction. An emergency exploratory laparotomy showed distended bowel loops,
      and multiple skip lesions from the terminal ileum to the ascending colon. PCR
      analyses showed Mycobacterium tuberculosis. The therapy regimen was unchanged
      after the operation; the patient gradually improved over the course of a month
      and was discharged without further symptoms thereafter.

PMID- 19095481
TI  - A paucity of co-infecting respiratory viral pathogens in nasopharyngeal specimens
      from patients infected with H274Y-positive influenza A (H1N1) strains.

PMID- 19095482
TI  - Intra-abdominal abscess caused by toothpick injury.
AB  - We present the case of a 42-year-old female who presented to our emergency
      department (ED) complaining of epigastric pain for four days. She had been seen
      in the outpatient department and ED previously for evaluation, but continued to
      experience epigastric pain with fever. Emergency panendoscopy was performed and a
      toothpick was discovered impacted in the duodenal bulb. The gastroenterologist
      was unable to remove the toothpick endoscopically. Computed tomography of the
      abdomen revealed a long and straight hyperdense foreign body, and intra-abdominal
      abscess formation. An emergency laparotomy was performed. The patient recovered
      gradually and was discharged 11 days later. She could not remember when she
      swallowed the wooden toothpick, but guessed that it was while out drinking. There
      is an old wives' tale in Taiwan that putting a toothpick in the cup while
      drinking beer reduces the likelihood of abdominal distention from the carbonation
      of the beer.

PMID- 19095483
TI  - Comment on Jing et al. original article "In vivo MR imaging tracking of magnetic
      iron oxide nanoparticle labeled, engineered, autologous bone marrow mesenchymal
      stem cells following intra-articular injection".

PMID- 19095484
TI  - [Aneurysmal carpal scaphoid cyst. A case report].
AB  - Aneurysmal bone cyst is a rare, benign bone tumor and its location in the carpal
      scaphoid has never been described in the literature. We report a clinical case
      illustrating this location.

PMID- 19095485
TI  - [Sciatic paralysis following uterine artery embolization].
AB  - Early postpartum bleeding remains in France the leading cause of maternal
      mortality in perinatal period. In association with obstetrical and medical
      measures to control bleeding, uterine arteries embolization constitutes an
      efficient non-surgical measure whose potential side effects must be kept in mind.
      We report the case of a patient that presented a popliteal sciatic paralysis in
      the hours following the procedure. Through this case, we will review the
      different types of embolization complications.

PMID- 19095486
TI  - Head and neck cancer information on the internet: type, accuracy and content.
AB  - This study aimed to determine the type, accuracy and content of information
      available on the internet regarding head and neck cancer. The search engine
      Google was used to generate a list of the top 100 websites about head and neck
      cancer. The websites were evaluated using the DISCERN instrument and the JAMA
      benchmarks and whether the site displayed the Health on the Net seal was also
      recorded. The search yielded 1,650,000 sites on the Google website. Of the top
      100 sites, a total of 33 sites were suitable for analysis due to duplicate links,
      non-functioning links and irrelevant website. 45% achieved all four JAMA
      benchmarks and 18% achieved only 1 benchmark. No website receiving the maximum
      mark on the overall score and four websites received the lowest overall score
      regarding the DISCERN instrument. The question with the poorest response score
      was 'Does it describe how the treatment choices affect overall quality of life?'
      39% of the websites displayed the Health on the Net (HON) seal. A wide variety of
      types of information are available on the internet regarding head and neck cancer
      with variable accuracy levels based on both Journal of the American Medical
      Association (JAMA) benchmarks and DISCERN. The onus lies with the practitioner to
      guide the patient regarding scientific reliability of information and to direct
      the patient in filtering the information sourced. The inclusion of quality of
      life related information is currently lacking and should be addressed to ensure a
      more comprehensive understanding for patients of treatment options.

PMID- 19095487
TI  - Detection of locoregional recurrent head and neck cancer after
      (chemo)radiotherapy using modern imaging.
AB  - After radiotherapy with or without chemotherapy differentiation between residual
      and recurrent head and neck cancer and (chemo)radiation sequelae is often
      difficult. Currently, most physicians aggressively pursue potential recurrences,
      leading to a high rate of futile invasive diagnostic, e.g. examinations under
      general anaesthesia with taking of biopsies, and surgical procedures, e.g.
      planned neck dissections, and a waste of health care resources. Therefore,
      diagnostic techniques which reliably select patients who should undergo these
      procedures are warranted. Conventional imaging techniques are not reliable enough
      for this purpose. Potential imaging techniques to detect residual and recurrent
      locoregional disease after chemoradiation are (serial) CT or MRI and FDG-PET,
      eventually in combination with specific response criteria or scoring systems.
      Diffusion MRI and PET/CT may further improve these techniques. FDG-PET may help
      to select patients clinically suspected of recurrent laryngeal carcinoma after
      radiotherapy for direct laryngoscopy under general anaesthesia. It is not yet
      clear whether FDG-PET can reliable avoid futile routine evaluation by examination
      under general anaesthesia in oral and oropharyngeal cancer and planned neck
      dissection when a residual mass persists in the neck after (chemo)radiation. The
      most reliable scoring criteria and the optimal time interval between completion
      of radiation and FDG-PET still has to be assessed.

PMID- 19095488
TI  - Recurrence interval affects survival after local relapse of oral cancer.
AB  - The aim of this study was to investigate whether the recurrence interval
      influenced survival rate of patients with relapse of oral squamous cell carcinoma
      (OSCC). From 1992 to 2006, a total of 773 patients with OSCC treated at the
      Department of Oral and Maxillofacial Plastic Surgery of the Ruhr-University
      Bochum were reviewed. Statistical analysis included descriptive statistics,
      Kaplan-Meier survival analyses, receiver operating characteristic, the Youden
      Index and analysis using the log-rank test and Cox-regression. The overall
      recurrence rate was 23.9%. Local recurrence was more common (64.9%) than
      locoregional recurrence (25.1%). Patients with relapse more than 18 months after
      completion of their primary treatment had significantly improved survival rates
      compared with those who relapsed within 18 months of initial treatment (20.5% vs
      42.3%). A significant difference was noted in the survival rate between patients
      with local and locoregional recurrence (37.5% vs 21.5%). Overall survival rate
      after salvage was 31.9%. The interval from initial treatment to recurrence is an
      independent prognostic factor for OSCC patients. Patients with a recurrence
      interval of 18 months had a statistically significant higher probability of death
      than those with a recurrence interval >18 months. This information can help
      inform salvage treatment strategies and provide a classification of early and
      late recurrences.

PMID- 19095490
TI  - Comorbidity and diagnostic delay in cancer of the larynx, tongue and pharynx.
AB  - Comorbidity and diagnostic delay are independent prognostic factors in head and
      neck cancer, most notably in laryngeal cancer. We investigated their inter
      relationship and their relative significance in survival of three different head
      and neck cancers. A population-based retrospective cohort of 221 patients with
      cancer of oral tongue, pharynx or larynx diagnosed between 1986 and 1996.
      Diagnostic delays and data on the onset of symptoms from real-time primary care
      charts. Comorbidity classified according to Charlson comorbidity index. Survival
      analyses were performed using Cox multivariate model. Significant association was
      found between increased comorbidity score and long professional delay in
      laryngeal cancer. In tongue cancer, longer patient delay and increased
      comorbidity were associated. In laryngeal cancer, high comorbidity (adjusted
      hazard ratio HR 5.6), professional delay of 6 months (HR 3.3) and advanced stage
      (HR 3.8) all were independent determinants of survival. In laryngeal cancer,
      comorbid illnesses are associated with professional diagnostic delay. However,
      despite their inter-correlation both comorbidity and professional delay are
      significant and independent prognostic factors.

PMID- 19095491
TI  - Comment on "Management of clinically negative neck for the patients with head and
      neck squamous cell carcinomas in the modern era" (Bar Ad V, Chalian A. Oral Oncol
      2008;44:817-22).

PMID- 19095489
TI  - Survival from salivary glands adenoid cystic carcinoma in European populations.
AB  - Adenoid cystic carcinoma (ACC) of salivary gland origin is rare. The EUROCARE
      data provide a good opportunity to study the survival of this uncommon cancer in
      a large population. A total of 2611 cases, aged 15 to 99 years, diagnosed between
      1983 and 1994 with primary salivary gland ACC were analyzed. Thirty-two
      population based cancer registries from seventeen countries participating in
      EUROCARE contributed the data. Relative survival by sex, age, period of
      diagnosis, region, site and stage, and the adjusted relative excess risk (RER) of
      death were estimated. Survival since diagnosis was 94%, 78% and 65% at 1, 5 and
      ten years, respectively. Ten-year survival was best (69%) in patients of the
      youngest age group (15-54 years) and from Northern Europe (69%). In the UK was
      higher (65%) than in Western (62%) and Eastern (56%) Europe. ACCs in nasal cavity
      (RER 2.6), pharynx (RER 3.5) and larynx and bronchus (RER 3.9) had a worse
      prognosis compared to those of oral cavity. A strong effect of stage at diagnosis
      on RERs and some worsening of survival at five years over time (80% in 1983-1985,
      76% in 1992-1994) were also evident. The findings of the present study, as those
      from clinical studies, confirm the important impact of primary site and stage at
      diagnosis on survival. Furthermore, we could demonstrate that survival for ACC
      did not improve over time and that cases from Eastern countries had a significant
      worse prognosis. Improvements in the disease detection in its early stage and
      international collaborative research should be encouraged.

PMID- 19095492
TI  - The effect of electrical stimulation therapy on dysphagia following treatment for
      head and neck cancer.
AB  - The purpose of this study was to evaluate the effect of neuromuscular electrical
      stimulation (NMES) in patients suffering from dysphagia following treatment for
      head and neck cancer. In a prospective, double blinded, randomized case control
      study between January 2006 and December 2007, 14 patients were randomized to
      30min of NMES and 30min of traditional swallowing training for 5 days per week
      for 2 weeks (experimental group), and 12 patients were randomized to sham
      stimulation plus traditional swallowing training (control group). Effects were
      assessed using the clinical dysphagia scale (CDS), the functional dysphagia scale
      (FDS), the American speech-language-hearing association national outcome
      measurement system (ASHA NOMS) and the M.D. Anderson dysphagia inventory (MADI).
      Pretreatment evaluation showed no significant differences between the two groups
      for all parameters. Average changes of FDS score were 11.4+/-8.1 for the
      experimental group and 3.3+/-14.0 for the control group (P=0.039). CDS, ASHA NOMS
      and MADI showed some difference with treatment, but the changes were not
      significant (P>0.05). NMES combined with traditional swallowing training is
      superior to traditional swallowing training alone in patients suffering from
      dysphagia following treatment for head and neck cancer.

PMID- 19095493
TI  - The 'inner circle' of the cereal genomes.
AB  - Early marker-based macrocolinearity studies between the grass genomes led to
      arranging their chromosomes into concentric 'crop circles' of synteny blocks that
      initially consisted of 30 rice-independent linkage groups representing the
      ancestral cereal genome structure. Recently, increased marker density and genome
      sequencing of several cereal genomes allowed the characterization of intragenomic
      duplications and their integration with intergenomic colinearity data to identify
      paleo-duplications and propose a model for the evolution of the grass genomes
      from a common ancestor. On the basis of these data an 'inner circle' comprising
      five ancestral chromosomes was defined providing a new reference for the grass
      chromosomes and new insights into their ancestral relationships and origin, as
      well as an efficient tool to design cross-genome markers for genetic studies.

PMID- 19095494
TI  - Stability of pyrene-1-carboxylic acid and other pyrene derivatives immobilized on
      silane gels.
AB  - The main aim of this research was to select a silane gel with appropriate
      composition containing fluorophore immobilized in it, in view of application of
      this carrier in the construction of a fluorescence optical sensor. Results of
      stationary fluorescence studies on gelation of silane gel with different
      composition, obtained as a result of acidic or basic hydrolysis using the
      fluorophores: pyrene-1-carboxylic acid and 1,3-bis(1-pyrenyl)propane, are
      presented. The form of probe during sol-gel transition and in the formed gel is
      discussed. The presence of a protonated form of PyCOOH(2)(+) was observed in the
      gel obtained by acidic hydrolysis and of PyCOO(-) ions and neutral form of PyCOOH
      in the gel obtained with the use of basic hydrolysis. The aim of the research was
      also to estimate suitability of the silane gel, which contained a selected
      immobilized fluorophore, for application in the optical sensor. This criterion
      includes determination of the kinetics of fluorophore elution from the gel as
      well as estimation of the interactions of fluorophore immobilized in the gel with
      microenvironment. Therefore, to carry out this part of the research, the silane
      gel was formed into a thin layer deposited on a glass surface. Next, the kinetics
      of elution of pyrene-1-carboxylic acid, 1,3-bis(1-pyrenyl)propane as well as
      pyrene and aminopyrene from this layers by water and ethanol was investigated.
      Elution rate constants were determined with the use of the first-order kinetics.
      Three stages of the elution with different duration were distinguished: I 0-4
      min, II 4 min-1h and III, the slowest one-above 1h. Stability of the probes
      immobilized in these gels during storage in water or ethanol for several days was
      also determined.

PMID- 19095495
TI  - Vibrational spectroscopic study of fluticasone propionate.
AB  - Fluticasone propionate is a synthetic glucocorticoid with potent anti
      inflammatory activity that has been used effectively in the treatment of chronic
      asthma. The present work reports a vibrational spectroscopic study of fluticasone
      propionate and gives proposed molecular assignments on the basis of ab initio
      calculations using BLYP density functional theory with a 6-31G* basis set and
      vibrational frequencies predicted within the quasi-harmonic approximation.
      Several spectral features and band intensities are explained. This study
      generated a library of information that can be employed to aid the process
      monitoring of fluticasone propionate.

PMID- 19095496
TI  - Patterns and changes in prescriber attitudes toward PDA prescription-assistive
      technology.
AB  - CONTEXT: Medication error prevention is a priority for the U.S. healthcare system
      in the 21st century. Use of technology is considered by some as critical to
      achieve this goal. Knowledge of the attitudinal barriers to such adoption,
      however, is limited. OBJECTIVE: To determine the attitudes of frontline
      prescriber clinicians towards technology in general, and PDAs specifically,
      before and after introduction of a PDA in the clinical setting of medication
      prescribing. DESIGN: A pre- and post-intervention web-based survey, 12-14 months
      apart. SETTING: Academic tertiary care children's hospital. PARTICIPANTS: Total
      of 244 prescriber clinicians. INTERVENTION: Distribution of a PDA with pediatric
      specific medication prescribing information after completion of an on-line
      medication safety certification and other safety focused educational sessions.
      MAIN OUTCOME MEASURES: Ratings (5-point Likert scale) reflecting perceptions and
      attitudes towards technology in general and technology in medical settings along
      with self-reported usage of the PDA for Rx. RESULTS: Early Adopters and Late
      Adopters were identified statistically, and the group membership reflected their
      prior exposure to and ownership of other technologies. Early Adopters tended to
      be younger and less experienced clinically (e.g., residents) and more frequent
      owners and users of technology. Early Adopters expressed significantly more
      favorable attitudes toward technology and PDAs on both pre- to post-intervention
      survey occasions. They also utilized the PDA for Rx more often than LAs.
      Interestingly, PDA use for Early Adopters was based on its ease of use, while PDA
      use among later adopters was based on its clinical usefulness. CONCLUSIONS:
      Provision of point of care information using PDAs and a user-friendly, pediatric
      specific medication information software package did not positively affect the
      attitudes of prescriber clinicians among those already favorable toward
      technology. However, a significant change was found among those with initially
      less favorable attitudes. Organizations need to understand the nature of both
      Early and Late Adopters and plan appropriately for managing the respective needs
      and expectations when potentially beneficial technologies are introduced. In
      order to ensure the success of an implementation, the training and supportive
      interventions need to be carefully designed and specifically catered to the
      personality-based outcome expectations of the prescriber.

PMID- 19095497
TI  - Efficacy and safety of sorafenib in patients in the Asia-Pacific region with
      advanced hepatocellular carcinoma: a phase III randomised, double-blind, placebo
      controlled trial.
AB  - BACKGROUND: Most cases of hepatocellular carcinoma occur in the Asia-Pacific
      region, where chronic hepatitis B infection is an important aetiological factor.
      Assessing the efficacy and safety of new therapeutic options in an Asia-Pacific
      population is thus important. We did a multinational phase III, randomised,
      double-blind, placebo-controlled trial to assess the efficacy and safety of
      sorafenib in patients from the Asia-Pacific region with advanced (unresectable or
      metastatic) hepatocellular carcinoma. METHODS: Between Sept 20, 2005, and Jan 31,
      2007, patients with hepatocellular carcinoma who had not received previous
      systemic therapy and had Child-Pugh liver function class A, were randomly
      assigned to receive either oral sorafenib (400 mg) or placebo twice daily in 6
      week cycles, with efficacy measured at the end of each 6-week period. Eligible
      patients were stratified by the presence or absence of macroscopic vascular
      invasion or extrahepatic spread (or both), Eastern Cooperative Oncology Group
      performance status, and geographical region. Randomisation was done centrally and
      in a 2:1 ratio by means of an interactive voice-response system. There was no
      predefined primary endpoint; overall survival, time to progression (TTP), time to
      symptomatic progression (TTSP), disease control rate (DCR), and safety were
      assessed. Efficacy analyses were done by intention to treat. This trial is
      registered with ClinicalTrials.gov, number NCT00492752. FINDINGS: 271 patients
      from 23 centres in China, South Korea, and Taiwan were enrolled in the study. Of
      these, 226 patients were randomly assigned to the experimental group (n=150) or
      to the placebo group (n=76). Median overall survival was 6.5 months (95% CI 5.56
      7.56) in patients treated with sorafenib, compared with 4.2 months (3.75-5.46) in
      those who received placebo (hazard ratio [HR] 0.68 [95% CI 0.50-0.93]; p=0.014).
      Median TTP was 2.8 months (2.63-3.58) in the sorafenib group compared with 1.4
      months (1.35-1.55) in the placebo group (HR 0.57 [0.42-0.79]; p=0.0005). The most
      frequently reported grade 3/4 drug-related adverse events in the 149 assessable
      patients treated with sorafenib were hand-foot skin reaction (HFSR; 16 patients
      [10.7%]), diarrhoea (nine patients [6.0%]), and fatigue (five patients [3.4%]).
      The most common adverse events resulting in dose reductions were HFSR (17
      patients [11.4%]) and diarrhoea (11 patients [7.4%]); these adverse events rarely
      led to discontinuation. INTERPRETATION: Sorafenib is effective for the treatment
      of advanced hepatocellular carcinoma in patients from the Asia-Pacific region,
      and is well tolerated. Taken together with data from the Sorafenib Hepatocellular
      Carcinoma Assessment Randomised Protocol (SHARP) trial, sorafenib seems to be an
      appropriate option for the treatment of advanced hepatocellular carcinoma.

PMID- 19095498
TI  - Anopheles mosquitoes: not just flying malaria vectors... especially in the field.
AB  - The polymorphism of genes involved in the immunity of malaria vectors has been
      the subject of several recent studies with mosquitoes from natural populations.
      Most of the genes examined are known for their role against Plasmodium berghei
      and not necessarily for their role against Plasmodium falciparum. It seems,
      therefore, to be highly important not only to be cautious when linking natural
      selection with malaria epidemiology but also to consider the importance of other
      parasites and the environment on the mosquito genome.

PMID- 19095499
TI  - Infection-control interventions for cancer patients after chemotherapy: a
      systematic review and meta-analysis.
AB  - To quantify the evidence for infection-control interventions among high-risk
      cancer patients and haematopoietic stem-cell recipients, we did a systematic
      review of prospective comparative studies. Protective isolation, including air
      quality control, prophylactic antibiotics, and barrier isolation (29 studies),
      brought about a significant reduction in all-cause mortality: risk ratio 0.60
      (95% CI 0.50-0.72) at 30 days (number needed to treat [NNT] 20 [95% CI 14-33])
      and 0.86 (95% CI 0.81-0.91) at the longest follow-up (up to 3 years; NNT 12 [95%
      CI 9-20]). Inclusion of prophylactic antibiotics in the intervention was
      necessary to show the effect on mortality. The combined intervention reduced
      bacteraemia, and Gram-negative, Gram-positive, and Candida spp infections. Mould
      infections were not significantly reduced. 11 non-randomised prospective studies
      assessed inpatient versus outpatient management after autologous stem-cell
      transplantation. All-cause mortality was lower among outpatients: risk ratio 0.72
      [95% CI 0.55-0.95]. We conclude that prophylactic antibiotics are the most
      effective treatment within the protective environment. Randomised trials on
      outpatient management of haematological cancer patients are needed.

PMID- 19095500
TI  - HRT and cardiovascular disease.
AB  - Hormone replacement therapy (HRT) has profound effects on the cardiovascular
      system, with plausible biological mechanisms explaining both the benefits and
      harm. Benefits may result from oestrogen action on metabolic risk factors, such
      as lipids, glucose and insulin metabolism, as well as direct arterial effects,
      reducing atherogenesis. Harm may arise from inappropriately high starting doses
      causing transient increases in coagulation activation and adverse vascular
      remodelling. Observational studies of HRT suggest that there is a beneficial
      effect on the incidence of coronary heart disease (CHD). Any benefit of HRT seen
      in randomized clinical trials appears to be confined to those women within
      several years of their menopause, and it is clear from the randomized trials that
      age at initiation is a crucially important consideration. Women initiating HRT
      within 10 years of menopause onset may achieve cardiovascular benefit,
      particularly in terms of primary CHD prevention, whilst avoiding risks of stroke
      and venous thrombo-embolism.

PMID- 19095501
TI  - Effects of hormone replacement therapy on connective tissue: why is this
      important?
AB  - Oestrogen deprivation has a negative effect on connective tissue and its
      turnover, although it can be difficult to distinguish these changes from those
      related to age. Such an effect can be prevented to some extent, and in some cases
      reversed, with oestrogen therapy. This has been shown to happen in the skin
      dermis, bone matrix, carotid artery media and intervertebral discs. This effect
      is also likely to extend to the extracellular non-collagenous matrix in all these
      systems, as oestrogen has profound effects on connective tissue turnover,
      regardless of the site. This has implications not only in maintaining the
      structure and aesthetic appearance of tissue, but also its strength and
      stiffness, and the functioning of neighbouring and surrounding organs. Large
      scale clinical trials are necessary to help make informed recommendations
      regarding postmenopausal oestrogen use and its role in connective tissue
      turnover.

PMID- 19095502
TI  - Effect of lipid core material on characteristics of solid lipid nanoparticles
      designed for oral lymphatic delivery.
AB  - Solid lipid nanoparticles (SLNs) are essentially composed of triglyceride(s) that
      orient to form a polar core with polar heads oriented toward the aqueous phase,
      resembling chylomicrons. The composition of such SLNs may alter the course of
      drug absorption predominantly to and through lymphatic route and regions,
      presumably following a transcellular path of lipid absorption, especially by
      enterocytes and polar epithelial cells of the intestine. SLNs were prepared using
      stearic acid, glycerol monostearate, tristearin, and Compritol 888 ATO by solvent
      diffusion method using demineralized double-distilled water as the dispersion
      medium. The SLNs were characterized for shape, size, zeta potential, and
      percentage drug content and its release. The characterization of SLNs suggests
      that Compritol 888 ATO-based nanoparticles were heterogeneous with better drug
      loading and release characteristics as compared with the other formulations. The
      selected products were studied for in vivo absorption and hence bioavailability
      by measure of area under the blood plasma curve plotted as a function of time.
      Periodic lymphatic concentration of drug following oral administration of
      respective formulations was also determined by mesenteric duct cannulation and
      collection of samples. The comparative study conducted on methotrexate (MTX)
      bearing SLNs revealed that the formulation based on Compritol 888 ATO could
      noticeably improve the oral bioavailability of MTX, presumably following SLNs
      constituting lipid digestion and co-absorption through lymphatic transport and
      route.

PMID- 19095503
TI  - Bile reflux after Roux-en-Y gastric bypass: an unrecognized cause of
      postoperative pain.
AB  - BACKGROUND: To determine, in a private practice, whether symptomatic bile reflux
      can occur after Roux-en-Y gastric bypass (RYGB) for morbid obesity and the
      outcome after laparoscopic alimentary (Roux) limb lengthening. Bile reflux as a
      cause of pain after laparoscopic RYGB has not been previously described. We
      report on a series of patients with chronic pain after RYGB as a result of bile
      reflux owing an abnormally short alimentary limb. METHODS: A prospective database
      of patients who underwent revisional surgery to treat symptomatic bile reflux at
      our center was retrospectively reviewed and analyzed for the onset of symptoms,
      interval to revision, length of alimentary limb, and outcome after revision.
      RESULTS: A total of 16 patients were diagnosed with bile reflux and underwent
      revisional surgery. The onset of symptoms occurred at 58.3 +/- 22.2 months after
      RYGB. All patients complained of pain, 13 (81.3%) had vomiting, and 7 (43.8%) had
      dysphagia. Endoscopy was performed in all patients and confirmed the presence of
      bile in all patients and detected marginal ulceration in 5 (31.3%) and gastritis
      in 8 (50.0%). At revisional surgery, the mean alimentary limb length was 37.7 +/-
      12.4 cm (range 20-62 cm). At a mean follow-up of 14.9 months after revision, all
      patients had reported resolution of their symptoms. CONCLUSION: Although
      previously unreported after RYGB, bile reflux can be an important possible cause
      of chronic pain. Bile reflux, however, responds favorably to alimentary limb
      lengthening to 100 cm and was not been seen in patients with an alimentary limb
      length >62 cm.

PMID- 19095504
TI  - Results of gastrojejunal anastomotic technique designed to reduce stricture.
AB  - BACKGROUND: The incidence of strictures developing after gastrojejunostomy has
      been reported to range from 3% to 31%. We found an unacceptably high stricture
      rate (13%) using a 21-mm circular stapler. Attempts to use the 25-mm circular
      stapler were frustrated by disparities between the size of the instrument and the
      patient's anatomy. We, therefore, modified the technique to accomplish the
      anastomosis with the linear stapler and hand sewing (LSA) at community hospitals
      in Southern California. METHODS: A total of 124 anastomoses were accomplished
      with the circular stapler (CSA) followed by 100 anastomoses using the LSA
      technique. Drains were used routinely with the CSA technique but were used only
      selectively with the LSA technique. Stricture was defined as that requiring
      endoscopic dilation for symptoms. Leaks were confirmed radiologically or
      surgically, and bleeding was defined as the need for transfusion. Our analysis
      used the Student t test and Fisher's exact test, with P <.05 considered
      statistically significant. RESULTS: No patient died. The LSA technique was faster
      and resulted in significantly fewer postoperative strictures and complications
      compared with the CSA technique. CONCLUSION: The results of our study have shown
      that the LSA technique, as described, is preferable to the CSA technique.

PMID- 19095505
TI  - Unrestricted insurance access to bariatric surgery: no more excuses.

PMID- 19095506
TI  - Preinductive use of clonidine and ketamine improves recovery and reduces
      postoperative pain after bariatric surgery.
AB  - BACKGROUND: In obese patients, concomitant use of clonidine and ketamine might be
      suitable to reduce the doses and minimize the undesired side effects of
      anesthetic and analgesic drugs. In this study, we evaluated the perioperative
      effects of administration of clonidine and ketamine in morbidly obese patients
      undergoing weight loss surgery at a university hospital in Rome, Italy. METHODS:
      A total of 50 morbidly obese patients undergoing open biliopancreatic diversion
      for weight loss surgery were enrolled. The patients were randomly allocated into
      a study group (n = 23) receiving a slow infusion of ketamine-clonidine before
      anesthesia induction and a control group (n = 27) who received standard
      anesthesia. The hemodynamic profile, intraoperative end-tidal sevoflurane and
      opioid consumption, tracheal extubation time, Aldrete score, postoperative pain
      assessment by visual analog scale, and analgesic requirements were recorded.
      RESULTS: The patients in the study group required less end-tidal sevoflurane,
      lower total doses of fentanyl (3.8 +/- 0.3 gamma/kg actual body weight versus 5.0
      +/- 0.2 gamma/kg actual body weight, respectively; P <.05) and had a shorter time
      to extubation (15.1 +/- 5 min versus 28.2 +/- 6 min, P <.05). The Aldrete score
      was significantly better in the postanesthesia care unit in the study group. The
      study group consumed less tramadol than did the control group (138 +/- 57 mg
      versus 252 +/- 78 mg, P <.05) and had a lower visual analog scale score
      postoperatively during the first 6 hours. CONCLUSION: The preoperative
      administration of low doses of ketamine and clonidine at induction appears to
      provide early extubation and diminished postoperative analgesic requirements in
      morbidly obese patients undergoing open bariatric surgery.

PMID- 19095507
TI  - Rapid quantification of miglustat in human plasma and cerebrospinal fluid by
      liquid chromatography coupled with tandem mass spectrometry.
AB  - Miglustat (OGT 918) is an iminosugar recently introduced in therapeutic as
      potential alternative therapy in disorders found in several diseases such as Tay
      Sachs, Gaucher or Niemann-Pick diseases. A highly sensitive liquid-chromatography
      electrospray tandem mass spectrometry (LC-MS/MS) assay was developed for the
      quantification of miglustat in human plasma and cerebrospinal fluid (CSF). The
      sample preparation consists in a simple protein precipitation with a mixture of
      acetonitrile/methanol (75/25) which yields 100% recovery. The isocratic
      separation utilizes an Atlantis Hilic (3 microm, 150 mm x 2.1 mm) column, with a
      mobile phase of acetonitrile/water/ammonium acetate buffer (75/10/15, v/v/v)
      delivered at 230 microl/min. Selected reaction monitoring (SRM) mode was used
      with the transitions m/z 220-->158 for the miglustat and m/z 208-->m/z 146 for
      the miglitol (internal standard). Good linearity was observed in a range from 125
      to 2500 ng/ml and from 50 to 1000 ng/ml, for plasma and CSF, respectively. The
      within-run precision of the assay was less than 6%, and the between-run run
      precision was less than 6.5%, for six replicates at each of three concentrations
      and evaluated on three separated days for both plasma and CSF mediums. Assay
      accuracy was in the range of 98-106.5%. Stability of miglustat was reported under
      a variety of storage conditions. The miglustat concentrations in two children are
      presented to demonstrate the clinical interest of this new method.

PMID- 19095509
TI  - Preparation and characterization of starch-poly-epsilon-caprolactone
      microparticles incorporating bioactive agents for drug delivery and tissue
      engineering applications.
AB  - One limitation associated with the delivery of bioactive agents concerns the
      short half-life of these molecules when administered intravenously, which results
      in their loss from the desired site. Incorporation of bioactive agents into depot
      vehicles provides a means to increase their persistence at the disease site.
      Major issues are involved in the development of a proper carrier system able to
      deliver the correct drug, at the desired dose, place and time. In this work,
      starch-poly-epsilon-caprolactone (SPCL) microparticles were developed for use in
      drug delivery and tissue engineering (TE) applications. SPCL microparticles were
      prepared by using an emulsion solvent extraction/evaporation technique, which was
      demonstrated to be a successful procedure to obtain particles with a spherical
      shape (particle size between 5 and 900 microm) and exhibiting different surface
      morphologies. Their chemical structure was confirmed by Fourier transform
      infrared spectroscopy. To evaluate the potential of the developed microparticles
      as a drug delivery system, dexamethasone (DEX) was used as model drug. DEX, a
      well-known component of osteogenic differentiation media, was entrapped into SPCL
      microparticles at different percentages up to 93%. The encapsulation efficiency
      was found to be dependent on the polymer concentration and drug-to-polymer ratio.
      The initial DEX release seems to be governed mainly by diffusion, and it is
      expected that the remaining DEX will be released when the polymeric matrix starts
      to degrade. In this work it was demonstrated that SPCL microparticles containing
      DEX can be successfully prepared and that these microparticular systems seem to
      be quite promising for controlled release applications, namely as carriers of
      important differentiation agents in TE.

PMID- 19095508
TI  - Direct profiling of tissue lipids by MALDI-TOFMS.
AB  - Advances in matrix-assisted laser desorption/ionization time-of-flight mass
      spectrometry (MALDI-TOFMS) have allowed for the direct analysis of biological
      molecules from tissue. Although most of the early studies of direct tissue
      profiling by MALDI-TOFMS have focused on proteins and peptides, analysis of
      lipids has increased dramatically in recent years. This review gives an overview
      of the factors to consider when analyzing lipids directly from tissue and some
      recent examples of the use of MALDI-TOFMS for the direct profiling of lipids in
      tissue.

PMID- 19095510
TI  - Outpatient general surgical follow-up: are we using this resource effectively?
AB  - BACKGROUND: Raised patient expectations and the 2-week rule for the investigation
      of suspected malignancy have led to heightened demands on surgical outpatient
      clinics. In this context, the utility of benign post-operative or investigative
      follow-ups requires justification. METHODS: The surgical outpatient clinic
      workload of four substantive general surgeons at a typical DGH was analysed over
      a 4-week period. All notes were examined to identify referral source, management
      plan and whether that clinic attendance was justified. RESULTS: Twenty three
      clinics (410 patients) were examined over the period of this study. Three hundred
      and twenty one patient episodes were examined; 52 episodes did not occur due to
      patient non-attendance and 37 episodes were not accounted for
      ('missing/incomplete data'). Thirty three percent of the patients underwent
      consultant review whilst 57% were reviewed by middle grade surgeons and 9% by
      SHO/ST2 doctors. Forty eight percent of the consultations were new referrals: 37%
      of these patients were added to the elective surgical waiting list. One hundred
      and sixty eight follow-up consultations occurred, which included cancer patients
      (6%), review patients (12%), patients attending for investigative results (13%)
      and benign post-operative follow-ups (22%). Forty six of the 69 (66%) post
      operative follow-ups were deemed unnecessary as patients were being seen after
      benign procedures (hernia repair, anorectal surgery or laparoscopic
      cholecystectomy). CONCLUSION: Over 50% attendances (21/41) for 'normal' results
      could have been avoided by the use of a directed informative letter. Outpatient
      clinics are an important resource whose usage must be optimised.

PMID- 19095511
TI  - Subacute hematoma after augmentation mammaplasty: case report.

PMID- 19095512
TI  - Superior orbital fissure syndrome after repair of maxillary and naso-orbito
      ethmoid fractures: a case study.
AB  - OBJECTIVE: The superior orbital fissure syndrome results from damage to the
      nerves passing through the superior orbital fissure. In the present case, the
      superior orbital fissure syndrome developed after repair of facial bone
      fractures, although the symptoms were not observed before surgery and no obvious
      cause was found. To investigate the aetiology of this syndrome, we examined the
      superior orbital fissure anatomically. METHODS: We measured the width of superior
      orbital fissure on the horizontal plane including the optic canal using the
      computed tomography (CT) scans of other patients and cadavers. RESULTS: The
      results indicated that the width was 3.73+/-1.64 mm in the CT scans of patients
      and 3.21+/-1.09 mm in the cadavers. There was no significant difference between
      the width in the CT scans and cadavers. The width in the present patient on the
      affected side was 1.6mm, that is relatively narrow. CONCLUSION: After operation,
      narrow superior orbital fissure may reduce the tolerance to compression of the
      nerves by oedema. We consider the narrow superior orbital fissure as a risk
      factor for superior orbital fissure syndrome. When the superior orbital fissure
      is congenitally narrow, the surgeons should try to avoid excessive pulling of the
      bone fragment and compression of the orbital tissue during repair of the facial
      bone fractures.

PMID- 19095513
TI  - Insulin therapy in type 2 diabetes is no longer a secondary care activity in the
      Netherlands.
AB  - AIM: Because Dutch health care organisations did want to establish well-defined
      diabetes shared care groups, we investigated the organisation of insulin therapy
      in general practice in the Netherlands and assessed factors that were associated
      with providing insulin therapy in type 2 diabetes (DM2) patients. METHODS:
      Questionnaire to half of the Dutch general practitioners (GPs) (n=3848). We
      compared GPs who both start insulin treatment and monitor the dosages with those
      who always refer patients requiring insulin therapy or only monitor insulin
      dosages. RESULTS: Total response was 42% (n=1621). 67% of the GPs start insulin
      therapy in patients with DM2, especially male GPs and those above the age of 40,
      as well as GPs working in a health centre and those working together with a
      practice nurse. GPs working in urban regions less often start insulin. The most
      often mentioned barriers for starting and/or monitoring insulin therapy are lack
      of knowledge of insulin therapy, lack of time and insufficient financial
      incentives. CONCLUSION: This nation-wide overview shows that insulin therapy is
      no longer a secondary care based activity. However, there is still need to
      enlarge the practice staff and to overcome the perceived skills deficit.

PMID- 19095514
TI  - A skeleton family generator via physics-based deformable models.
AB  - This paper presents a novel approach for object skeleton family extraction. The
      introduced technique utilizes a 2-D physics-based deformable model that
      parameterizes the objects shape. Deformation equations are solved exploiting
      modal analysis, and proportional to model physical characteristics, a different
      skeleton is produced every time, generating, in this way, a family of skeletons.
      The theoretical properties and the experiments presented demonstrate that
      obtained skeletons match to hand-labeled skeletons provided by human subjects,
      even in the presence of significant noise and shape variations, cuts and tears,
      and have the same topology as the original skeletons. In particular, the proposed
      approach produces no spurious branches without the need of any known skeleton
      pruning method.

PMID- 19095515
TI  - Variational bayesian blind deconvolution using a total variation prior.
AB  - In this paper, we present novel algorithms for total variation (TV) based blind
      deconvolution and parameter estimation utilizing a variational framework. Using a
      hierarchical Bayesian model, the unknown image, blur, and hyperparameters for the
      image, blur, and noise priors are estimated simultaneously. A variational
      inference approach is utilized so that approximations of the posterior
      distributions of the unknowns are obtained, thus providing a measure of the
      uncertainty of the estimates. Experimental results demonstrate that the proposed
      approaches provide higher restoration performance than non-TV-based methods
      without any assumptions about the unknown hyperparameters.

PMID- 19095516
TI  - Image sequence denoising via sparse and redundant representations.
AB  - In this paper, we consider denoising of image sequences that are corrupted by
      zero-mean additive white Gaussian noise. Relative to single image denoising
      techniques, denoising of sequences aims to also utilize the temporal dimension.
      This assists in getting both faster algorithms and better output quality. This
      paper focuses on utilizing sparse and redundant representations for image
      sequence denoising, extending the work reported in. In the single image setting,
      the K-SVD algorithm is used to train a sparsifying dictionary for the corrupted
      image. This paper generalizes the above algorithm by offering several extensions:
      i) the atoms used are 3-D; ii) the dictionary is propagated from one frame to the
      next, reducing the number of required iterations; and iii) averaging is done on
      patches in both spatial and temporal neighboring locations. These modifications
      lead to substantial benefits in complexity and denoising performance, compared to
      simply running the single image algorithm sequentially. The algorithm's
      performance is experimentally compared to several state-of-the-art algorithms,
      demonstrating comparable or favorable results.

PMID- 19095517
TI  - Generalizing the nonlocal-means to super-resolution reconstruction.
AB  - Super-resolution reconstruction proposes a fusion of several low-quality images
      into one higher quality result with better optical resolution. Classic super
      resolution techniques strongly rely on the availability of accurate motion
      estimation for this fusion task. When the motion is estimated inaccurately, as
      often happens for nonglobal motion fields, annoying artifacts appear in the super
      resolved outcome. Encouraged by recent developments on the video denoising
      problem, where state-of-the-art algorithms are formed with no explicit motion
      estimation, we seek a super-resolution algorithm of similar nature that will
      allow processing sequences with general motion patterns. In this paper, we base
      our solution on the Nonlocal-Means (NLM) algorithm. We show how this denoising
      method is generalized to become a relatively simple super-resolution algorithm
      with no explicit motion estimation. Results on several test movies show that the
      proposed method is very successful in providing super-resolution on general
      sequences.

PMID- 19095518
TI  - Subband weighting with pixel connectivity for 3-D wavelet coding.
AB  - Performing optimal bit-allocation with 3-D wavelet coding methods is difficult
      because energy is not conserved after applying the motion-compensated temporal
      filtering (MCTF) process and the spatial wavelet transform. The problem cannot be
      solved by extending the 2-D wavelet coefficients weighting method directly and
      then applying the result to 3-D wavelet coefficients, since this approach does
      not consider the complicated pixel connectivity that results from the lifting
      based MCTF process. In this paper, we propose a novel weighting method, which
      takes account of the pixel connectivity, to solve the problem and derive the
      effect of the quantization error of a subband on the reconstruction error of a
      group of pictures. We employ the proposed method on a 2-D + t structure with
      different temporal filters, namely the 5-3 filter and the 9-7 filter. Experiments
      on various coding parameters and sequences show that the proposed approach
      improves the bit-allocation performance over that obtained by using the
      weightings derived without considering the pixel connectivity in the MCTF
      process.

PMID- 19095519
TI  - Joint optimization of run-length coding, Huffman coding, and quantization table
      with complete baseline JPEG decoder compatibility.
AB  - To maximize rate distortion performance while remaining faithful to the JPEG
      syntax, the joint optimization of the Huffman tables, quantization step sizes,
      and DCT indices of a JPEG encoder is investigated. Given Huffman tables and
      quantization step sizes, an efficient graph-based algorithm is first proposed to
      find the optimal DCT indices in the form of run-size pairs. Based on this graph
      based algorithm, an iterative algorithm is then presented to jointly optimize run
      length coding, Huffman coding, and quantization table selection. The proposed
      iterative algorithm not only results in a compressed bitstream completely
      compatible with existing JPEG and MPEG decoders, but is also computationally
      efficient. Furthermore, when tested over standard test images, it achieves the
      best JPEG compression results, to the extent that its own JPEG compression
      performance even exceeds the quoted PSNR results of some state-of-the-art wavelet
      based image coders such as Shapiro's embedded zerotree wavelet algorithm at the
      common bit rates under comparison. Both the graph-based algorithm and the
      iterative algorithm can be applied to application areas such as web image
      acceleration, digital camera image compression, MPEG frame optimization, and
      transcoding, etc.

PMID- 19095520
TI  - Down-sampling design in DCT domain with arbitrary ratio for image/video
      transcoding.
AB  - This paper proposes a designing framework for down-sampling compressed
      images/video with arbitrary ratio in the discrete cosine transform (DCT) domain.
      In this framework, we first derive a set of DCT-domain down-sampling methods
      which can be represented by a linear transform with double-sided matrix
      multiplication (LTDS) in the DCT domain and show that the set contains a wide
      range of methods with various complexity and visual quality. Then, for a
      preselected spatial-domain down-sampling method, we formulate an optimization
      problem for finding an LTDS to approximate the given spatial-domain down-sampling
      method for a trade-off between the visual quality and the complexity. By modeling
      LTDS as a multiple layer network, a so-called structural learning with forgetting
      algorithm is then applied to solve the optimization problem. The proposed
      framework has been applied to discover optimal LTDSs corresponding to a spatial
      down-sampling method with Butterworth low-pass filtering and bicubic
      interpolation. Experimental results show that the resulting LTDS achieves a
      significant reduction on the complexity when compared with other methods in the
      literature with similar visual quality.

PMID- 19095521
TI  - Joint source-channel distortion modeling for MPEG-4 video.
AB  - Multimedia communication has become one of the main applications in commercial
      wireless systems. Multimedia sources, mainly consisting of digital images and
      videos, have high bandwidth requirements. Since bandwidth is a valuable resource,
      it is important that its use should be optimized for image and video
      communication. Therefore, interest in developing new joint source-channel coding
      (JSCC) methods for image and video communication is increasing. Design of any
      JSCC scheme requires an estimate of the distortion at different source coding
      rates and under different channel conditions. The common approach to obtain this
      estimate is via simulations or operational rate-distortion curves. These
      approaches, however, are computationally intensive and, hence, not feasible for
      real-time coding and transmission applications. A more feasible approach to
      estimate distortion is to develop models that predict distortion at different
      source coding rates and under different channel conditions. Based on this idea,
      we present a distortion model for estimating the distortion due to quantization
      and channel errors in MPEG-4 compressed video streams at different source coding
      rates and channel bit error rates. This model takes into account important
      aspects of video compression such as transform coding, motion compensation, and
      variable length coding. Results show that our model estimates distortion within
      1.5 dB of actual simulation values in terms of peak-signal-to-noise ratio.

PMID- 19095523
TI  - Event-by-event image reconstruction from list-mode PET data.
AB  - This paper adapts the classical list-mode OSEM and the globally convergent list
      mode COSEM methods to the special case of singleton subsets. The image estimate
      is incrementally updated for each coincidence event measured by the PET scanner.
      Events are used as soon as possible to improve the current image estimate, and,
      therefore, the convergence speed toward the maximum-likelihood solution is
      accelerated. An alternative online formulation of the list-mode COSEM algorithm
      is proposed first. This method saves memory resources by re-computing previous
      incremental image contributions while processing a new pass over the complete
      dataset. This online expectation-maximization principle is applied to the list
      mode OSEM method, as well. Image reconstructions have been performed from a
      simulated dataset for the NCAT torso phantom and from a clinical dataset. Results
      of the classical and event-by-event list-mode algorithms are discussed in a
      systematic and quantitative way.

PMID- 19095522
TI  - Accurate distortion estimation and optimal bandwidth allocation for scalable
      H.264 video transmission over MIMO systems.
AB  - In this paper, we propose an optimal strategy for the transmission of scalable
      video over packet-based multiple-input multiple-output (MIMO) systems. The
      scalable extension of H.264/AVC that provides a combined temporal, quality and
      spatial scalability is used. For given channel conditions, we develop a method
      for the estimation of the distortion of the received video and propose different
      error concealment schemes. We show the accuracy of our distortion estimation
      algorithm in comparison with simulated wireless video transmission with packet
      errors. In the proposed MIMO system, we employ orthogonal space-time block codes
      (O-STBC) that guarantee independent transmission of different symbols within the
      block code. In the proposed constrained bandwidth allocation framework, we use
      the estimated end-to-end decoder distortion to optimally select the application
      layer parameters, i.e., quantization parameter (QP) and group of pictures (GOP)
      size, and physical layer parameters, i.e., rate-compatible turbo (RCPT) code rate
      and symbol constellation. Results show the substantial performance gain by using
      different symbol constellations across the scalable layers as compared to a fixed
      constellation.

PMID- 19095524
TI  - A unifying approach to moment-based shape orientation and symmetry
      classification.
AB  - In this paper, the problem of moment-based shape orientation and symmetry
      classification is jointly considered. A generalization and modification of
      current state-of-the-art geometric moment-based functions is introduced. The
      properties of these functions are investigated thoroughly using Fourier series
      analysis and several observations and closed-form solutions are derived. We
      demonstrate the connection between the results presented in this work and
      symmetry detection principles suggested from previous complex moment-based
      formulations. The proposed analysis offers a unifying framework for shape
      orientation/symmetry detection. In the context of symmetry classification and
      matching, the second part of this work presents a frequency domain method, aiming
      at computing a robust moment-based feature set based on a true polar Fourier
      representation of image complex gradients and a novel periodicity detection
      scheme using subspace analysis. The proposed approach removes the requirement for
      accurate shape centroid estimation, which is the main limitation of moment-based
      methods, operating in the image spatial domain. The proposed framework
      demonstrated improved performance, compared to state-of-the-art methods.

PMID- 19095525
TI  - Correspondence propagation with weak priors.
AB  - For the problem of image registration, the top few reliable correspondences are
      often relatively easy to obtain, while the overall matching accuracy may fall
      drastically as the desired correspondence number increases. In this paper, we
      present an efficient feature matching algorithm to employ sparse reliable
      correspondence priors for piloting the feature matching process. First, the
      feature geometric relationship within individual image is encoded as a spatial
      graph, and the pairwise feature similarity is expressed as a bipartite similarity
      graph between two feature sets; then the geometric neighborhood of the pairwise
      assignment is represented by a categorical product graph, along which the
      reliable correspondences are propagated; and finally a closed-form solution for
      feature matching is deduced by ensuring the feature geometric coherency as well
      as pairwise feature agreements. Furthermore, our algorithm is naturally
      applicable for incorporating manual correspondence priors for semi-supervised
      feature matching. Extensive experiments on both toy examples and real-world
      applications demonstrate the superiority of our algorithm over the state-of-the
      art feature matching techniques.

PMID- 19095526
TI  - Improvements in shape-from-focus for holographic reconstructions with regard to
      focus operators, neighborhood-size, and height value interpolation.
AB  - This paper presents a shape-from-focus method, which is improved with regard to
      the mathematical operator used for contrast measurement, the selection of the
      neighborhood size, surface refinement through interpolation, and surface
      postprocessing. Three-dimensional models of living human faces are presented with
      such a high resolution that single hairs are visible.

PMID- 19095527
TI  - Independent component analysis-based background subtraction for indoor
      surveillance.
AB  - In video surveillance, detection of moving objects from an image sequence is very
      important for target tracking, activity recognition, and behavior understanding.
      Background subtraction is a very popular approach for foreground segmentation in
      a still scene image. In order to compensate for illumination changes, a
      background model updating process is generally adopted, and leads to extra
      computation time. In this paper, we propose a fast background subtraction scheme
      using independent component analysis (ICA) and, particularly, aims at indoor
      surveillance for possible applications in home-care and health-care monitoring,
      where moving and motionless persons must be reliably detected. The proposed
      method is as computationally fast as the simple image difference method, and yet
      is highly tolerable to changes in room lighting. The proposed background
      subtraction scheme involves two stages, one for training and the other for
      detection. In the training stage, an ICA model that directly measures the
      statistical independency based on the estimations of joint and marginal
      probability density functions from relative frequency distributions is first
      proposed. The proposed ICA model can well separate two highly-correlated images.
      In the detection stage, the trained de-mixing vector is used to separate the
      foreground in a scene image with respect to the reference background image. Two
      sets of indoor examples that involve switching on/off room lights and
      opening/closing a door are demonstrated in the experiments. The performance of
      the proposed ICA model for background subtraction is also compared with that of
      the well-known FastICA algorithm.

PMID- 19095528
TI  - Estimation of motions in color image sequences using hypercomplex fourier
      transforms.
AB  - Although the motion estimation problem has been extensively studied, most of the
      proposed estimation approaches deal mainly with monochrome videos. The most usual
      way to apply them also in color image sequences is to process each color channel
      separately. A different, more sophisticated approach is to process the color
      channels in a "holistic" manner using quaternions, as proposed by Ell and
      Sangwine. In this paper, we extend standard spatiotemporal Fourier-based
      approaches to handle color image sequences, using the hypercomplex Fourier
      transform. We show that translational motions are manifested as energy
      concentration along planes in the hypercomplex 3-D Fourier domain and we describe
      a methodology to estimate the motions, based on this property. Furthermore, we
      compare the three-channels-separately approach with our approach and we show that
      the computational effort can be reduced by a factor of 1/3, using the
      hypercomplex Fourier transform. Also, we propose a simple, accompanying method to
      extract the moving objects in the hypercomplex Fourier domain. Our experimental
      results on synthetic and natural images verify our arguments throughout the
      paper.

PMID- 19095529
TI  - A sparsity-enforcing method for learning face features.
AB  - In this paper, we propose a new trainable system for selecting face features from
      over-complete dictionaries of image measurements. The starting point is an
      iterative thresholding algorithm which provides sparse solutions to linear
      systems of equations. Although the proposed methodology is quite general and
      could be applied to various image classification tasks, we focus here on the case
      study of face and eyes detection. For our initial representation, we adopt
      rectangular features in order to allow straightforward comparisons with existing
      techniques. For computational efficiency and memory saving requirements, instead
      of implementing the full optimization scheme on tenths of thousands of features,
      we propose a three-stage architecture which consists of finding first
      intermediate solutions to smaller size optimization problems, then merging the
      obtained results, and next applying further selection procedures. The devised
      system requires the solution of a number of independent problems, and, hence, the
      necessary computations could be implemented in parallel. Experimental results
      obtained on both benchmark and newly acquired face and eyes images indicate that
      our method is a serious competitor to other feature selection schemes recently
      popularized in computer vision for dealing with problems of real-time object
      detection. A major advantage of the proposed system is that it performs well even
      with relatively small training sets.

PMID- 19095530
TI  - Improved block truncation coding based on the void-and-cluster dithering
      approach.
AB  - Block Truncation Coding (BTC) is an efficient technology for image compression.
      An improved BTC algorithm, namely Ordered Dither Block Truncation Coding (ODBTC),
      is presented in this study. In order to provide better image quality, the void
      and-cluster halftoning is combined with the BTC. The ODBTC results show that the
      image quality is improved when it is operated in high coding gain applications.
      Another feature of the ODBTC is the dither array Look Up Table (LUT), which
      significantly reduces the complexity compared to the BTC.

PMID- 19095531
TI  - Comments on "optimal erasure protection for scalably compressed video streams
      with limited retransmission".
AB  - In order to prove a key result for their development (Lemma 2), Taubman and Thie
      need the assumption that the upper boundary of the convex hull of the channel
      coding probability-redundancy characteristic is sufficiently dense. Since a floor
      value for the density level for which the claim to hold is not specified, it is
      not clear whether their lemma applies to practical situations. In this
      correspondence, we show that the constraint of sufficient density can be removed,
      and, thus, we validate the conclusion of the lemma for any scenario encountered
      in practice.

PMID- 19095532
TI  - Uncorrelated multilinear discriminant analysis with regularization and
      aggregation for tensor object recognition.
AB  - This paper proposes an uncorrelated multilinear discriminant analysis (UMLDA)
      framework for the recognition of multidimensional objects, known as tensor
      objects. Uncorrelated features are desirable in recognition tasks since they
      contain minimum redundancy and ensure independence of features. The UMLDA aims to
      extract uncorrelated discriminative features directly from tensorial data through
      solving a tensor-to-vector projection. The solution consists of sequential
      iterative processes based on the alternating projection method, and an adaptive
      regularization procedure is incorporated to enhance the performance in the small
      sample size (SSS) scenario. A simple nearest-neighbor classifier is employed for
      classification. Furthermore, exploiting the complementary information from
      differently initialized and regularized UMLDA recognizers, an aggregation scheme
      is adopted to combine them at the matching score level, resulting in enhanced
      generalization performance while alleviating the regularization parameter
      selection problem. The UMLDA-based recognition algorithm is then empirically
      shown on face and gait recognition tasks to outperform four multilinear subspace
      solutions (MPCA, DATER, GTDA, TR1DA) and four linear subspace solutions
      (Bayesian, LDA, ULDA, R-JD-LDA).

PMID- 19095533
TI  - Robust label propagation on multiple networks.
AB  - Transductive inference on graphs such as label propagation algorithms is
      receiving a lot of attention. In this paper, we address a label propagation
      problem on multiple networks and present a new algorithm that automatically
      integrates structure information brought in by multiple networks. The proposed
      method is robust in that irrelevant networks are automatically deemphasized,
      which is an advantage over Tsuda's approach (2005). We also show that the
      proposed algorithm can be interpreted as an expectation-maximization (EM)
      algorithm with a student-t prior. Finally, we demonstrate the usefulness of our
      method in protein function prediction and digit classification, and show
      analytically and experimentally that our algorithm is much more efficient than
      existing algorithms.

PMID- 19095534
TI  - Necessary and sufficient convergence conditions for algebraic image
      reconstruction algorithms.
AB  - The Landweber scheme is an algebraic reconstruction method and includes several
      important algorithms as its special cases. The convergence of the Landweber
      scheme is of both theoretical and practical importance. Using the singular value
      decomposition (SVD), we derive an iterative representation formula for the
      Landweber scheme and consequently establish the necessary and sufficient
      conditions for its convergence. In addition to verifying the necessity and
      sufficiency of known convergent conditions, we find new convergence conditions
      allowing relaxation coefficients in an interval not covered by known results.
      Moreover, it is found that the Landweber scheme can converge within finite
      iterations when the relaxation coefficients are chosen to be the inverses of
      squares of the nonzero singular values. Furthermore, the limits of the Landweber
      scheme in all convergence cases are shown to be the sum of the minimum norm
      solution of a weighted least-squares problem and an oblique projection of the
      initial image onto the null space of the system matrix.

PMID- 19095535
TI  - Automated geospatial conflation of vector road maps to high resolution imagery.
AB  - As the availability of various geospatial data increases, there is an urgent need
      to integrate multiple datasets to improve spatial analysis. However, since these
      datasets often originate from different sources and vary in spatial accuracy,
      they often do not match well to each other. In addition, the spatial discrepancy
      is often nonsystematic such that a simple global transformation will not solve
      the problem. Manual correction is labor-intensive and time-consuming and often
      not practical. In this paper, we present an innovative solution for a vector-to
      imagery conflation problem by integrating several vector-based and image-based
      algorithms. We only extract the different types of road intersections and
      terminations from imagery based on spatial contextual measures. We eliminate the
      process of line segment detection which is often troublesome. The vector road
      intersections are matched to these detected points by a relaxation labeling
      algorithm. The matched point pairs are then used as control points to perform a
      piecewise rubber-sheeting transformation. With the end points of each road
      segment in correct positions, a modified snake algorithm maneuvers intermediate
      vector road vertices toward a candidate road image. Finally a refinement
      algorithm moves the points to center each road and obtain better cartographic
      quality. To test the efficacy of the automated conflation algorithm, we used U.S.
      Census Bureau's TIGER vector road data and U.S. Department of Agriculture's 1-m
      multi-spectral near infrared aerial photography in our study. Experiments were
      conducted over a variety of rural, suburban, and urban environments. The results
      demonstrated excellent performance. The average correctness measure increased
      from 20.6% to 95.5% and the average root-mean-square error decreased from 51.2 to
      3.4 m.

PMID- 19095536
TI  - K-means clustering versus validation measures: a data-distribution perspective.
AB  - K-means is a well-known and widely used partitional clustering method. While
      there are considerable research efforts to characterize the key features of the K
      means clustering algorithm, further investigation is needed to understand how
      data distributions can have impact on the performance of K-means clustering. To
      that end, in this paper, we provide a formal and organized study of the effect of
      skewed data distributions on K-means clustering. Along this line, we first
      formally illustrate that K-means tends to produce clusters of relatively uniform
      size, even if input data have varied "true" cluster sizes. In addition, we show
      that some clustering validation measures, such as the entropy measure, may not
      capture this uniform effect and provide misleading information on the clustering
      performance. Viewed in this light, we provide the coefficient of variation (CV)
      as a necessary criterion to validate the clustering results. Our findings reveal
      that K-means tends to produce clusters in which the variations of cluster sizes,
      as measured by CV, are in a range of about 0.3-1.0. Specifically, for data sets
      with large variation in "true" cluster sizes (e.g., CV > 1.0), K-means reduces
      variation in resultant cluster sizes to less than 1.0. In contrast, for data sets
      with small variation in "true" cluster sizes (e.g., CV < 0.3), K-means increases
      variation in resultant cluster sizes to greater than 0.3. In other words, for the
      earlier two cases, K-means produces the clustering results which are away from
      the "true" cluster distributions.

PMID- 19095537
TI  - A new approach for overlay text detection and extraction from complex video
      scene.
AB  - Overlay text brings important semantic clues in video content analysis such as
      video information retrieval and summarization, since the content of the scene or
      the editor's intention can be well represented by using inserted text. Most of
      the previous approaches to extracting overlay text from videos are based on low
      level features, such as edge, color, and texture information. However, existing
      methods experience difficulties in handling texts with various contrasts or
      inserted in a complex background. In this paper, we propose a novel framework to
      detect and extract the overlay text from the video scene. Based on our
      observation that there exist transient colors between inserted text and its
      adjacent background, a transition map is first generated. Then candidate regions
      are extracted by a reshaping method and the overlay text regions are determined
      based on the occurrence of overlay text in each candidate. The detected overlay
      text regions are localized accurately using the projection of overlay text pixels
      in the transition map and the text extraction is finally conducted. The proposed
      method is robust to different character size, position, contrast, and color. It
      is also language independent. Overlay text region update between frames is also
      employed to reduce the processing time. Experiments are performed on diverse
      videos to confirm the efficiency of the proposed method.

PMID- 19095538
TI  - Multiresolution image representation using combined 2-D and 1-D directional
      filter banks.
AB  - In this paper, effective multiresolution image representations using a
      combination of 2-D filter bank (FB) and directional wavelet transform (WT) are
      presented. The proposed methods yield simple implementation and low computation
      costs compared to previous 1-D and 2-D FB combinations or adaptive directional WT
      methods. Furthermore, they are nonredundant transforms and realize quad-tree like
      multiresolution representations. In applications on nonlinear approximation,
      image coding, and denoising, the proposed filter banks show visual quality
      improvements and have higher PSNR than the conventional separable WT or the
      contourlet.

PMID- 19095539
TI  - Shearlet-based total variation diffusion for denoising.
AB  - We propose a shearlet formulation of the total variation (TV) method for
      denoising images. Shearlets have been mathematically proven to represent
      distributed discontinuities such as edges better than traditional wavelets and
      are a suitable tool for edge characterization. Common approaches in combining
      wavelet-like representations such as curvelets with TV or diffusion methods aim
      at reducing Gibbs-type artifacts after obtaining a nearly optimal estimate. We
      show that it is possible to obtain much better estimates from a shearlet
      representation by constraining the residual coefficients using a projected
      adaptive total variation scheme in the shearlet domain. We also analyze the
      performance of a shearlet-based diffusion method. Numerical examples demonstrate
      that these schemes are highly effective at denoising complex images and
      outperform a related method based on the use of the curvelet transform.
      Furthermore, the shearlet-TV scheme requires far fewer iterations than similar
      competitors.

PMID- 19095540
TI  - Exploratory undersampling for class-imbalance learning.
AB  - Undersampling is a popular method in dealing with class-imbalance problems, which
      uses only a subset of the majority class and thus is very efficient. The main
      deficiency is that many majority class examples are ignored. We propose two
      algorithms to overcome this deficiency. EasyEnsemble samples several subsets from
      the majority class, trains a learner using each of them, and combines the outputs
      of those learners. BalanceCascade trains the learners sequentially, where in each
      step, the majority class examples that are correctly classified by the current
      trained learners are removed from further consideration. Experimental results
      show that both methods have higher Area Under the ROC Curve, F-measure, and G
      mean values than many existing class-imbalance learning methods. Moreover, they
      have approximately the same training time as that of undersampling when the same
      number of weak classifiers is used, which is significantly faster than other
      methods.

PMID- 19095541
TI  - A dynamic method to forecast the wheel slip for antilock braking system and its
      experimental evaluation.
AB  - The control of an antilock braking system (ABS) is a difficult problem due to its
      strongly nonlinear and uncertain characteristics. To overcome this difficulty,
      the integration of gray-system theory and sliding-mode control is proposed in
      this paper. This way, the prediction capabilities of the former and the
      robustness of the latter are combined to regulate optimal wheel slip depending on
      the vehicle forward velocity. The design approach described is novel, considering
      that a point, rather than a line, is used as the sliding control surface. The
      control algorithm is derived and subsequently tested on a quarter vehicle model.
      Encouraged by the simulation results indicating the ability to overcome the
      stated difficulties with fast convergence, experimental results are carried out
      on a laboratory setup. The results presented indicate the potential of the
      approach in handling difficult real-time control problems.

PMID- 19095542
TI  - Reinforcement learning versus model predictive control: a comparison on a power
      system problem.
AB  - This paper compares reinforcement learning (RL) with model predictive control
      (MPC) in a unified framework and reports experimental results of their
      application to the synthesis of a controller for a nonlinear and deterministic
      electrical power oscillations damping problem. Both families of methods are based
      on the formulation of the control problem as a discrete-time optimal control
      problem. The considered MPC approach exploits an analytical model of the system
      dynamics and cost function and computes open-loop policies by applying an
      interior-point solver to a minimization problem in which the system dynamics are
      represented by equality constraints. The considered RL approach infers in a model
      free way closed-loop policies from a set of system trajectories and instantaneous
      cost values by solving a sequence of batch-mode supervised learning problems. The
      results obtained provide insight into the pros and cons of the two approaches and
      show that RL may certainly be competitive with MPC even in contexts where a good
      deterministic system model is available.

PMID- 19095543
TI  - Boosted online learning for face recognition.
AB  - Face recognition applications commonly suffer from three main drawbacks: a
      reduced training set, information lying in high-dimensional subspaces, and the
      need to incorporate new people to recognize. In the recent literature, the
      extension of a face classifier in order to include new people in the model has
      been solved using online feature extraction techniques. The most successful
      approaches of those are the extensions of the principal component analysis or the
      linear discriminant analysis. In the current paper, a new online boosting
      algorithm is introduced: a face recognition method that extends a boosting-based
      classifier by adding new classes while avoiding the need of retraining the
      classifier each time a new person joins the system. The classifier is learned
      using the multitask learning principle where multiple verification tasks are
      trained together sharing the same feature space. The new classes are added taking
      advantage of the structure learned previously, being the addition of new classes
      not computationally demanding. The present proposal has been (experimentally)
      validated with two different facial data sets by comparing our approach with the
      current state-of-the-art techniques. The results show that the proposed online
      boosting algorithm fares better in terms of final accuracy. In addition, the
      global performance does not decrease drastically even when the number of classes
      of the base problem is multiplied by eight.

PMID- 19095544
TI  - Delay-distribution-dependent stability and stabilization of T-S fuzzy systems
      with probabilistic interval delay.
AB  - In this paper, we are concerned with the problem of stability analysis and
      stabilization control design for Takagi-Sugeno (T-S) fuzzy systems with
      probabilistic interval delay. By employing the information of probability
      distribution of the time delay, the original system is transformed into a T-S
      fuzzy model with stochastic parameter matrices. Based on the new type of T-S
      fuzzy model, the delay-distribution-dependent criteria for the mean-square
      exponential stability of the considered systems are derived by using the Lyapunov
      Krasovskii functional method, parallel distributed compensation approach, and the
      convexity of some matrix equations. The solvability of the derived criteria
      depends not only on the size of the delay but also on the probability
      distribution of the delay taking values in some intervals. The revisions of the
      main criteria in this paper can also be used to deal with the case when only the
      information of variation range of the delay is considered. It is shown by
      practical examples that our method can lead to very less conservative results
      than those by other existing methods.

PMID- 19095545
TI  - Multiagent optimization system for solving the traveling salesman problem (TSP).
AB  - The multiagent optimization system (MAOS) is a nature-inspired method, which
      supports cooperative search by the self-organization of a group of compact agents
      situated in an environment with certain sharing public knowledge. Moreover, each
      agent in MAOS is an autonomous entity with personal declarative memory and
      behavioral components. In this paper, MAOS is refined for solving the traveling
      salesman problem (TSP), which is a classic hard computational problem. Based on a
      simplified MAOS version, in which each agent manipulates on extremely limited
      declarative knowledge, some simple and efficient components for solving TSP,
      including two improving heuristics based on a generalized edge assembly
      recombination, are implemented. Compared with metaheuristics in adaptive memory
      programming, MAOS is particularly suitable for supporting cooperative search. The
      experimental results on two TSP benchmark data sets show that MAOS is competitive
      as compared with some state-of-the-art algorithms, including the Lin-Kernighan
      Helsgaun, IBGLK, PHGA, etc., although MAOS does not use any explicit local search
      during the runtime. The contributions of MAOS components are investigated. It
      indicates that certain clues can be positive for making suitable selections
      before time-consuming computation. More importantly, it shows that the
      cooperative search of agents can achieve an overall good performance with a macro
      rule in the switch mode, which deploys certain alternate search rules with the
      offline performance in negative correlations. Using simple alternate rules may
      prevent the high difficulty of seeking an omnipotent rule that is efficient for a
      large data set.

PMID- 19095546
TI  - SQualTrack: a tool for robust fault detection.
AB  - One of the techniques used to detect faults in dynamic systems is analytical
      redundancy. An important difficulty in applying this technique to real systems is
      dealing with the uncertainties associated with the system itself and with the
      measurements. In this paper, this uncertainty is taken into account by the use of
      intervals for the parameters of the model and for the measurements. The method
      that is proposed in this paper checks the consistency between the system's
      behavior, obtained from the measurements, and the model's behavior; if they are
      inconsistent, then there is a fault. The problem of detecting faults is stated as
      a quantified real constraint satisfaction problem, which can be solved using the
      modal interval analysis (MIA). MIA is used because it provides powerful tools to
      extend the calculations over real functions to intervals. To improve the results
      of the detection of the faults, the simultaneous use of several sliding time
      windows is proposed. The result of implementing this method is SemiQUALitative
      TRACKing (SQualTrack), a fault-detection tool that is robust in the sense that it
      does not generate false alarms, i.e., if there are false alarms, they indicate
      either that the interval model does not represent the system adequately or that
      the interval measurements do not represent the true values of the variables
      adequately. SQualTrack is currently being used to detect faults in real
      processes. Some of these applications using real data have been developed within
      the European project Advanced Decision Support System for Chemical/Petrochemical
      Manufacturing Processes and are also described in this paper.

PMID- 19095547
TI  - Novel robust stability criteria for stochastic Hopfield neural networks with time
      delays.
AB  - In this paper, the problem of asymptotic stability for stochastic Hopfield neural
      networks (HNNs) with time delays is investigated. New delay-dependent stability
      criteria are presented by constructing a novel Lyapunov-Krasovskii functional.
      Moreover, the results are further extended to the delayed stochastic HNNs with
      parameter uncertainties. The main idea is based on the delay partitioning
      technique, which differs greatly from most existing results and reduces
      conservatism. Numerical examples are provided to illustrate the effectiveness and
      less conservativeness of the developed techniques.

PMID- 19095548
TI  - Construction of tunable radial basis function networks using orthogonal forward
      selection.
AB  - An orthogonal forward selection (OFS) algorithm based on leave-one-out (LOO)
      criteria is proposed for the construction of radial basis function (RBF) networks
      with tunable nodes. Each stage of the construction process determines an RBF
      node, namely, its center vector and diagonal covariance matrix, by minimizing the
      LOO statistics. For regression application, the LOO criterion is chosen to be the
      LOO mean-square error, while the LOO misclassification rate is adopted in two
      class classification application. This OFS-LOO algorithm is computationally
      efficient, and it is capable of constructing parsimonious RBF networks that
      generalize well. Moreover, the proposed algorithm is fully automatic, and the
      user does not need to specify a termination criterion for the construction
      process. The effectiveness of the proposed RBF network construction procedure is
      demonstrated using examples taken from both regression and classification
      applications.

PMID- 19095549
TI  - Guaranteed cost control of polynomial fuzzy systems via a sum of squares
      approach.
AB  - This paper presents the guaranteed cost control of polynomial fuzzy systems via a
      sum of squares (SOS) approach. First, we present a polynomial fuzzy model and
      controller that are more general representations of the well-known Takagi-Sugeno
      (T-S) fuzzy model and controller, respectively. Second, we derive a guaranteed
      cost control design condition based on polynomial Lyapunov functions. Hence, the
      design approach discussed in this paper is more general than the existing LMI
      approaches (to T-S fuzzy control system designs) based on quadratic Lyapunov
      functions. The design condition realizes a guaranteed cost control by minimizing
      the upper bound of a given performance function. In addition, the design
      condition in the proposed approach can be represented in terms of SOS and is
      numerically (partially symbolically) solved via the recent developed SOSTOOLS. To
      illustrate the validity of the design approach, two design examples are provided.
      The first example deals with a complicated nonlinear system. The second example
      presents micro helicopter control. Both the examples show that our approach
      provides more extensive design results for the existing LMI approach.

PMID- 19095550
TI  - Efficient population utilization strategy for particle swarm optimizer.
AB  - The particle swarm optimizer (PSO) is a population-based optimization technique
      that can be applied to a wide range of problems. This paper presents a variation
      on the traditional PSO algorithm, called the efficient population utilization
      strategy for PSO (EPUS-PSO), adopting a population manager to significantly
      improve the efficiency of PSO. This is achieved by using variable particles in
      swarms to enhance the searching ability and drive particles more efficiently.
      Moreover, sharing principals are constructed to stop particles from falling into
      the local minimum and make the global optimal solution easier found by particles.
      Experiments were conducted on unimodal and multimodal test functions such as
      Quadric, Griewanks, Rastrigin, Ackley, and Weierstrass, with and without
      coordinate rotation. The results show good performance of the EPUS-PSO in solving
      most benchmark problems as compared to other recent variants of the PSO.

PMID- 19095551
TI  - Adaptive neural control for a class of uncertain nonlinear systems in pure
      feedback form with hysteresis input.
AB  - In this paper, adaptive neural control is investigated for a class of unknown
      nonlinear systems in pure-feedback form with the generalized Prandtl-Ishlinskii
      hysteresis input. To deal with the nonaffine problem in face of the nonsmooth
      characteristics of hysteresis, the mean-value theorem is applied successively,
      first to the functions in the pure-feedback plant, and then to the hysteresis
      input function. Unknown uncertainties are compensated for using the function
      approximation capability of neural networks. The unknown virtual control
      directions are dealt with by Nussbaum functions. By utilizing Lyapunov synthesis,
      the closed-loop control system is proved to be semiglobally uniformly ultimately
      bounded, and the tracking error converges to a small neighborhood of zero.
      Simulation results are provided to illustrate the performance of the proposed
      approach.

PMID- 19095552
TI  - A volume-based heat-diffusion classifier.
AB  - Heat-diffusion models have been successfully applied to various domains such as
      classification and dimensionality-reduction tasks in manifold learning. One
      critical local approximation technique is employed to weigh the edges in the
      graph constructed from data points. This approximation technique is based on an
      implicit assumption that the data are distributed evenly. However, this
      assumption is not valid in most cases, so the approximation is not accurate in
      these cases. To solve this challenging problem, we propose a volume-based heat
      diffusion model (VHDM). In VHDM, the volume is theoretically justified by
      handling the input data that are unevenly distributed on an unknown manifold. We
      also propose a novel volume-based heat-diffusion classifier (VHDC) based on VHDM.
      One of the advantages of VHDC is that the computational complexity is linear on
      the number of edges given a constructed graph. Moreover, we give an analysis on
      the stability of VHDC with respect to its three free parameters, and we
      demonstrate the connection between VHDC and some other classifiers. Experiments
      show that VHDC performs better than Parzen window approach, K nearest neighbor,
      and the HDC without volumes in prediction accuracy and outperforms some recently
      proposed transductive-learning algorithms. The enhanced performance of VHDC shows
      the validity of introducing the volume. The experiments also confirm the
      stability of VHDC with respect to its three free parameters.

PMID- 19095553
TI  - Correlative linear neighborhood propagation for video annotation.
AB  - Recently, graph-based semisupervised learning methods have been widely applied in
      multimedia research area. However, for the application of video semantic
      annotation in multilabel setting, these methods neglect an important
      characteristic of video data: The semantic concepts appear correlatively and
      interact naturally with each other rather than exist in isolation. In this paper,
      we adapt this semantic correlation into graph-based semisupervised learning and
      propose a novel method named correlative linear neighborhood propagation to
      improve annotation performance. Experiments conducted on the Text REtrieval
      Conference VIDeo retrieval evaluation data set have demonstrated its
      effectiveness and efficiency.

PMID- 19095554
TI  - Comprehensive unified control strategy for underactuated two-link manipulators.
AB  - This paper presents a unified treatment of the motion control of underactuated
      two-link manipulators, including acrobots and pendubots. The motion space is
      divided into two areas: swing-up and attractive; and control laws are designed
      for each. First, a control law based on a weak-control Lyapunov function (WCLF)
      is employed to increase the energy of and control the posture of the actuated
      link in the swing-up area. Next, one parameter of the WCLF is chosen to be a
      nonlinear function of the state to avoid singularities. Then, another parameter
      of the control law is adjusted based on the state to improve the control
      performance. Finally, an optimal control law is designed for the attractive area.
      Stability is guaranteed in the swing-up area by the use of a WCLF based on
      LaSalle's invariance principle. Moreover, the global stability of the control
      system is guaranteed by integrating the WCLF and a nonsmooth Lyapunov function.

PMID- 19095555
TI  - Tracking by parts: a bayesian approach with component collaboration.
AB  - Instead of using global-appearance information for visual tracking, as adopted by
      many methods, we propose a tracking-by-parts (TBP) approach that uses partial
      appearance information for the task. The proposed method considers the
      collaborations between parts and derives a probability propagation framework by
      encoding the spatial coherence in a Bayesian formulation. To resolve this
      formulation, a TBP particle-filtering method is introduced. Unlike existing
      methods that only use the spatial-coherence relationship for particle-weight
      estimation, our method further applies this relationship for state prediction
      based on system dynamics. Thus, the part-based information can be utilized
      efficiently, and the tracking performance can be improved. Experimental results
      show that our approach outperforms the factored-likelihood and particle reweight
      methods, which only use spatial coherence for weight estimation.

PMID- 19095556
TI  - Adaptive fuzzy output-feedback controller design for nonlinear time-delay systems
      with unknown control direction.
AB  - In this paper, the robust-control problem is investigated for a class of
      uncertain nonlinear time-delay systems via dynamic output-feedback approach. The
      considered system is in the strict-feedback form with unknown control direction.
      A full-order observer is constructed with the gains computed via linear matrix
      inequality at first. Then, with the bounds of uncertain functions known, we
      design the dynamic output-feedback controller such that the closed-loop system is
      asymptotically stable. Furthermore, when the bound functions of uncertainties are
      not available, the adaptive fuzzy-logic system is employed to approximate the
      uncertain function, and the corresponding output-feedback controller is designed.
      It is shown that the resulting closed-loop system is stable in the sense of
      semiglobal uniform ultimate boundedness. Finally, simulations are done to verify
      the feasibility and effectiveness of the obtained theoretical results.

PMID- 19095557
TI  - Transmission rate allocation in multisensor target tracking over a shared
      network.
AB  - In a multisensor target tracking application running on a shared network, at what
      bit rates should the sensors send their measurements to the tracking fusion
      center? Clearly, the sensors cannot use arbitrary rates in a shared network, and
      a standard network rate control algorithm may not provide rates amenable to
      effective target tracking. For Kalman filter-based multisensor target tracking,
      we derive a utility function that captures the tracking quality of service as a
      function of the sensor bit rates. We incorporate this utility function into a
      network rate resource allocation framework, deriving a distributed rate control
      algorithm for a shared network that is suitable for current best effort packet
      networks, such as the Internet. In simulation studies, the new rate control
      algorithm engenders significantly better tracking performance than a standard
      rate control method, while the ordinary data transfer flows continue to
      effectively operate while using their standard rate control methods.

PMID- 19095558
TI  - Neural network control of mobile robot formations using RISE feedback.
AB  - In this paper, an asymptotically stable (AS) combined kinematic/torque control
      law is developed for leader-follower-based formation control using backstepping
      in order to accommodate the complete dynamics of the robots and the formation,
      and a neural network (NN) is introduced along with robust integral of the sign of
      the error feedback to approximate the dynamics of the follower as well as its
      leader using online weight tuning. It is shown using Lyapunov theory that the
      errors for the entire formation are AS and that the NN weights are bounded as
      opposed to uniformly ultimately bounded stability which is typical with most NN
      controllers. Additionally, the stability of the formation in the presence of
      obstacles is examined using Lyapunov methods, and by treating other robots in the
      formation as obstacles, collisions within the formation do not occur. The
      asymptotic stability of the follower robots as well as the entire formation
      during an obstacle avoidance maneuver is demonstrated using Lyapunov methods, and
      numerical results are provided to verify the theoretical conjectures.

PMID- 19095559
TI  - Tumor amount in prostatic tissues in relation to patient outcome and management.

PMID- 19095560
TI  - Refining our criteria: a critical challenge.

PMID- 19095561
TI  - The role of multiparameter flow cytometry for detection of minimal residual
      disease in acute myeloid leukemia.
AB  - The presence of minimal residual disease (MRD) in the bone marrow (BM) of
      patients with acute myeloid leukemia (AML) following chemotherapy has been
      established by many studies to be strongly associated with relapse of leukemia.
      In addition, detection of MRD is the major objective of many of the newer
      diagnostic techniques used in malignant hematology. Because of the wide
      availability and conceptual straightforwardness of immunophenotyping, flow
      cytometry is the most accessible method for MRD detection. This review is not an
      overview of all MRD studies, but rather discusses the possibilities for
      optimizing MRD detection, the use of multiparameter flow cytometry (MFC)
      techniques in MRD detection, and the implications for future patient treatment.
      This review focuses on MRD detection in AML using MFC and discusses the reported
      correlations of MRD, clinical and biologic features of the disease, and outcome.
      In addition, it discusses the laboratory and clinical aspects of this approach.

PMID- 19095562
TI  - Small B-cell neoplasms with typical mantle cell lymphoma immunophenotypes often
      include chronic lymphocytic leukemias.
AB  - Mantle cell lymphoma (MCL) and chronic lymphocytic leukemia (CLL) are CD5+ small
      B-cell neoplasms (SBCNs) with overlapping features. Flow cytometric
      immunophenotyping is often used to help differentiate CLL from MCL, and a
      characteristic CLL phenotype is considered essentially diagnostic. However,
      previous studies have not specifically examined how well a typical MCL
      immunophenotype distinguishes MCL from CLL. We identified 28 cases of SBCN with
      typical flow cytometry-determined MCL immunophenotypes consisting mostly of
      peripheral blood and bone marrow specimens. Fluorescence in situ hybridization
      analysis indicated that 57% (16/28) had t(11;14) translocations consistent with
      MCL, while 32% (9/28) lacked t(11;14) translocations but harbored other
      cytogenetic abnormalities commonly found in CLL. There were no significant
      morphologic or immunophenotypic differences between the t(11;14)-positive and
      t(11;14)-negative cases. Our findings suggest that many blood-based SBCNs with
      typical MCL immunophenotypes likely represent cases of phenotypically atypical
      CLL, which would have important clinical implications.

PMID- 19095563
TI  - Germinal-center T-helper-cell markers PD-1 and CXCL13 are both expressed by
      neoplastic cells in angioimmunoblastic T-cell lymphoma.
AB  - Gene expression profiling identified genes uniquely expressed by human germinal
      center T-helper (GCTh) cells, including programmed death-1 (PD-1) and CXCL13.
      Recently, we demonstrated that PD-1 is an immunophenotypic marker of GCTh cells
      and angioimmunoblastic T-cell lymphoma (AITL). The goal of this study was to
      investigate the expression pattern of CXCL13 in comparison with PD-1. We studied
      63 cases of T-cell lymphoproliferative disorders, including 22 cases of AITL. In
      cases of AITL, PD-1+ and CXCL13+ neoplastic cells were seen at foci of expanded
      CD21+ follicular dendritic cell networks. CXCL13 expression was limited in other
      peripheral T-cell lymphomas. PD-1 and CXCL13 identified germinal-center T-helper
      cells, showed a similar pattern of expression in AITL, and should serve as useful
      new markers for AITL. The similar pattern of expression of CXCL13 and PD-1 in
      AITL provides further evidence that AITL is a neoplasm derived from germinal
      center T-helper cells.

PMID- 19095564
TI  - Prevalence of elevated hemoglobin A2 measured by the CAPILLARYS system.
AB  - Hemoglobin (Hb) A2 electrophoresis has been used for prenatal screening for the
      beta-thalassemia trait (betaTT). We retrospectively reviewed Hb capillary
      electrophoresis performed in our laboratory. We found that of the 122 cases
      showing elevated HbA2 levels, 79 cases were due to hemoglobinopathies, mostly
      HbS. Review of the RBC indices suggested that 3 of 36 cases with elevation of
      HbA2 in the HbAA-pregnancy group had betaTT and 29 had normal RBC indices; data
      were not available for 4 patients. Among 7 cases with elevation of HbA2 in the
      HbAA-other group, 5 had betaTT and 2 were normal. The number of patients without
      betaTT but with HbA2 elevation in the pregnant group was significantly higher
      than that in the nonpregnant group. When a higher HbA2 cutoff (3.5%) was used,
      only 3 pregnant patients without betaTT had HbA2 elevation, similar to the
      nonpregnant group. We found that a significant number of pregnant women with mild
      HbA2 elevation had no evidence of betaTT, compared with the nonpregnant group.

PMID- 19095565
TI  - Detection of isolated tumor cells in neuroblastoma by immunohistochemical
      analysis in bone marrow biopsy specimens: improved detection with use of beta
      catenin.
AB  - Evaluation of the bone marrow is a critical component of accurate staging and
      surveillance for recurrent disease in neuroblastoma. The value of routine
      immunohistochemical analysis of otherwise histologically negative bone marrow
      biopsy specimens has not been adequately evaluated. By using synaptophysin,
      chromogranin, and beta-catenin, immunohistochemical analysis performed on
      otherwise histologically negative bone marrow specimens identified isolated tumor
      cells (ITCs) in 9.1%, 5.0%, and 10.0% of 220 biopsy specimens, respectively.
      Overall survival, as estimated by the Kaplan-Meier method, was not significantly
      different between patients with and without ITCs (P = .357). Of the
      immunohistochemical markers evaluated, beta-catenin showed the greatest
      sensitivity for identifying ITCs in the bone marrow and showed reactivity in
      primary tumor samples. We found that the presence of ITCs identified by
      immunohistochemical analysis may predict the persistence of disease but does not
      show significant overall survival differences. We also identified beta-catenin as
      a sensitive immunohistochemical marker of primary and metastatic neuroblastoma.

PMID- 19095566
TI  - The clinical reliability of automated cerebrospinal fluid cell counts on the
      Beckman-Coulter LH750 and Iris iQ200.
AB  - Although automation has improved the accuracy and precision of blood cell counts
      and is more rapid and less labor-intensive, cerebrospinal fluid (CSF) samples are
      still counted manually. We compared the IRIS iQ200 Body Fluids Module (Iris
      Diagnostics, Chatsworth, CA) and the Beckman-Coulter LH750 (Beckman-Coulter,
      Brea, CA) with manual counts and evaluated the impact of automation on the
      laboratory if clinically acceptable performance was to be maintained. Automated
      counts were compared with manual counts on 313 specimens. Clinical reliability
      was estimated using the weighted kappa coefficient and the impact of errors
      discussed in the context of a historic census of 3,653 samples spanning 19
      months. Nucleated cell counts had a reliability of 0.73 for the LH750 and 0.84
      for the iQ200. However, our results showed unacceptable rates of error at counts
      less than 200/microL (200 x 106/L) for the LH750 and less than 50/microL (50 x
      106/L) for the iQ200, representing 94% and 83% of the census specimens,
      respectively. If clinical reliability is to be maintained, neither the LH750 nor
      iQ200 would have a significant impact on improving the efficiency of the
      laboratory because of the high percentage of low CSF cell counts.

PMID- 19095567
TI  - A bcr3/short form PML-RARalpha transcript in an acute promyelocytic leukemia
      resulted from a derivative chromosome 17 due to submicroscopic insertion of the
      PML gene into the RARalpha locus.
AB  - Acute promyelocytic leukemia (APL) is a subtype of acute myeloid leukemia.
      Submicroscopic insertion of RARalpha into PML, resulting in PML-RARalpha from
      derivative chromosome 15, has been rarely reported. Herein, we describe a
      functional PML-RARalpha transcript from the long arm of derivative chromosome 17
      in a patient with microgranular APL. The conventional karyotype showed normal
      chromosomes 15 and 17. It is interesting that interphase and metaphase
      fluorescence in situ hybridizations demonstrated a fusion signal on the long arm
      of one chromosome 17 homolog, with both PML and RARalpha still present on
      chromosomes 15 and 17, respectively, although the signal on one chromosome 15 was
      weaker, indicating partial loss of the PML gene. Reverse transcriptase-polymerase
      chain reaction revealed a transcript corresponding to a break cluster region 3
      (bcr3) short form PML-RARalpha. To the best of our knowledge, this is the first
      report of an APL with a bcr3/short form PML-RARalpha transcript generated from
      derivative chromosome 17 due to submicroscopic insertion of the PML gene into the
      RARalpha locus.

PMID- 19095568
TI  - Relevance of serology for Mycoplasma pneumoniae diagnosis compared with PCR and
      culture in acute exacerbation of bronchial asthma.
AB  - We studied Mycoplasma pneumoniae as the etiologic pathogen in acute exacerbations
      of asthma and the value of polymerase chain reaction (PCR), culture, and
      serologic tests for its accurate diagnosis. For the study, 59 nonsmoking patients
      with asthma (37 females, 22 males; age, 15-50 years) underwent clinical,
      radiologic, and laboratory examinations. Bacteria isolated from sputum were
      Streptococcus pneumoniae (32 [54%]), Staphylococcus aureus (23 [39%]), and M
      pneumoniae (5 [15%]). All M pneumoniae were associated with S pneumoniae (8/32
      [25%]) and S aureus (1/23 [4%]). No M pneumoniae were isolated as single
      pathogens. Serologic testing for M pneumoniae revealed that all samples were
      positive for specific IgG; 40 (68%) had a high titer, and 19 (32%) had a moderate
      titer. Of 59 samples, 29 (49%) were positive by Serodia Myco II gelatin particle
      testing (Fujirebio, Tokyo, Japan). PCR was positive in 25 samples, all of which
      had a high IgG titer; all culture-positive cases were PCR+. M pneumoniae is a
      common bacterial pathogen associated with acute exacerbations of asthma in people
      15 years or older. Prompt laboratory diagnosis of M pneumoniae requires direct
      detection by PCR and culture. A high serologic titer can be a clue for the
      presence of M pneumoniae.

PMID- 19095569
TI  - Evaluation of enzyme immunoassays to detect Clostridium difficile toxin from
      anaerobic stool culture.
AB  - Stool culture for Clostridium difficile, while necessary for strain typing and
      antimicrobial surveillance, cannot determine toxin production. We prospectively
      tested in triplicate 91 C difficile cultured isolates for toxin production by 2
      enzyme immunoassays (EIAs) (Meridian Premier Toxins A&B, Meridian Bioscience,
      Cincinnati, OH; and TechLab Tox A/B II, TechLab, Blacksburg, VA) and cytotoxin
      neutralization bioassay (CTN). By CTN, 88% (80/91) were toxigenic.
      Reproducibility was 93% (85/91) for CTN, 80% (73/91) for Meridian EIA, and 79%
      (72/91) for TechLab EIA. Compared with CTN, sensitivities were 87.1% and 89.2%
      for the Meridian and TechLab EIAs, respectively. In an additional 115 stool
      specimens, CTN detected toxin more frequently from cultured isolates (96/115)
      than stool (84/115). For C difficile toxin detection from isolates, EIA was less
      reproducible than CTN. EIA methods can be falsely negative in 10% to 12% of
      isolates, and these should be tested by CTN or polymerase chain reaction. When
      positive, EIA is fast and reliable for detecting C difficile toxin from culture.

PMID- 19095570
TI  - Percentage of tumor in prostatectomy specimens: a study of American Veterans.
AB  - In this study, I have estimated the percentage of tumor by visual estimate in 447
      prostatectomy specimens from American Veterans Affairs patients and related this
      measurement to overall survival. Although percentage of tumor was significantly
      related to the serum prostate-specific antigen level, tumor stage, and Gleason
      score-that is, it was not statistically independent from these-it was more
      closely associated with overall survival than any of them. Altogether, 2
      variables available at the time of the prostatectomy related to survival: patient
      age (P = .0032; Cox proportional hazards model analysis) and percentage of tumor
      (P = .0013; Cox model). Patient age undoubtedly reflects the combination of
      comorbidities and general expected length of life. Percentage of tumor, by
      contrast, seems to efficiently reflect any undue hazard for early death due to
      prostate cancer. The results suggest that percentage of tumor is a useful
      prognostic variable for understanding risk of early death after prostatectomy.

PMID- 19095571
TI  - Lymphatic vessel density as prognostic marker in esophageal adenocarcinoma.
AB  - We studied tumor lymphatic vascular density (LVD) as a predictive marker for the
      risk of lymph node (LN) metastasis and its relationship to other prognostic
      parameters and survival in 75 patients with esophageal adenocarcinoma. Samples
      were immunostained for D2-40, CD31, and vascular endothelial growth factor
      (VEGF). Microvessels were counted in densely vascular/lymphatic foci (hot spots)
      at x400 field (0.17 mm2). Intensity of staining for VEGF was scored on a 2-tiered
      scale. CD31 microvessel counts showed significant correlation with tumor stage
      and patient survival (P < .01). D2-40 LVD demonstrated a significant correlation
      with LN metastases, lymphovascular invasion, and tumor stage (r = 0.45, r = 0.47,
      and r = 0.37, respectively) and with shorter disease-free survival. D2-40
      detected lymphovascular invasion in 29 of 75 cases, more than with CD31 (23/75)
      and H&E (18/75). VEGF was expressed in 48 (64%) of 75 cases and was significantly
      correlated with lymphovascular invasion, LN metastases, and overall survival. Our
      study showed that angiogenesis and lymphangiogenesis have important roles in the
      progression of esophageal adenocarcinoma.

PMID- 19095572
TI  - Lack of clinical usefulness of Das-1 monoclonal antibody and mucin expression as
      risk markers of gastric carcinoma in patients with gastric intestinal metaplasia.
AB  - Our aim was to evaluate the usefulness of the monoclonal antibody Das-1 as a
      premalignant marker of gastric intestinal metaplasia (GIM) associated with
      gastric cancer and its association with mucin expression. We evaluated Das-1 and
      mucin expression in 4 groups: 1 (n = 50), gastric carcinoma, paired samples of
      the cancer area and GIM away from the tumor; 2 (n = 25), gastric or duodenal
      ulcer with Helicobacter pylori infection with GIM and chronic gastritis; 3 (n =
      25),H pylori- autoimmune chronic atrophic gastritis with GIM; and 4 (n = 25),H
      pylori- chronic gastritis without GIM. Das-1 immunostaining was observed in 20
      (40%) of 50 cases in cancer areas. The expression of Das-1 in GIM from group 1
      cases away from the cancer area was different from that in GIM from nontumor
      cases (groups 2 and 3): 13 (26%) of 50 vs 2 (8%) and 0 (0%) of 25 (P = .004).
      There was no association between Das-1 and mucin expression. Das-1 expression was
      associated with GIM from patients with gastric cancer. However, this relation was
      weaker than previously reported, precluding clinical usefulness as a premalignant
      marker of GIM.

PMID- 19095573
TI  - External quality assurance of HER2 FISH and ISH testing: three years of the UK
      national external quality assurance scheme.
AB  - The American Society of Clinical Oncology/College of American Pathologists
      guidelines highlighted the critical importance of quality assurance in diagnostic
      testing for HER2. Unstained formalin-fixed, paraffin-embedded human breast
      carcinoma cell line sections were circulated to scheme participants on 9
      occasions. "Reference laboratories" reported results for the HER2/chromosome 17
      ratio and HER2 copy number for 3 years for each cell line, including 418 sets of
      results (1,671 results total). The number of participants was 62 laboratories in
      the final analysis. The mean and SD of results from reference laboratories
      demonstrated consistency during the 3-year period. The percentage of laboratories
      achieving "appropriate" results ranged from 45% to 88%, and the percentage
      achieving "inappropriate" results ranged from 5% to 29%. No consistent effect of
      the HER2 in situ hybridization testing method was demonstrated. Participation in
      external quality assurance schemes is a valuable mechanism for demonstrating and
      acquiring consistency for HER2 testing by in situ hybridization. Poor performance
      can be corrected via assistance and advice.

PMID- 19095574
TI  - Extent and histologic pattern of atypical ductal hyperplasia present on core
      needle biopsy specimens of the breast can predict ductal carcinoma in situ in
      subsequent excision.
AB  - Atypical ductal hyperplasia (ADH) diagnosed by core needle biopsy (CNB) is
      regarded as an indication for surgical excision. We investigated whether
      histologic subtype and extent of ADH in a series of 123 CNB specimens can predict
      the presence of carcinoma on surgical excision. We found that ADH present in more
      than 2 foci in CNB specimens was a strong predictor of ductal carcinoma in situ
      (DCIS) on excision (>2 foci, 16/41 vs 6/82 for 1 or 2 foci; P < .0001). The
      micropapillary subtype of ADH also predicted the presence of DCIS (P = .0006).
      Our study suggests that micropapillary histologic subtype and extent of ADH in
      CNB specimens can be applied to predict the presence of DCIS on surgical
      excision. By using the combination of the extent of ADH in CNB specimens (1 or 2
      foci), the presence of microcalcifications within the lesion, and the lack of
      residual mammographic calcifications after CNB, we identified a low-risk group of
      patients (n = 25), none of whom had carcinoma on surgical excision. Patients with
      ADH restricted to fewer than 3 foci may not need surgical excision, especially
      when the mammographic abnormality is completely removed by CNB.

PMID- 19095575
TI  - Evidence-based criteria to help distinguish metastatic breast cancer from primary
      lung adenocarcinoma on thoracic frozen section.
AB  - The distinction between primary lung adenocarcinoma and metastatic breast
      carcinoma in patients with a history of breast cancer is difficult by frozen
      section (FS) analysis. Our experience with 129 FSs from 121 patients with a
      pulmonary nodule and a history of breast cancer was reviewed. The pretest odds
      ratio of primary pulmonary carcinoma/metastatic breast carcinoma was 2.6. The
      incidence of 12 histopathologic features was assessed in a "training set"
      composed of 20 FSs, 10 with primary lung adenocarcinoma and 10 with metastatic
      breast cancer. A differential diagnosis model composed of significant pathologic
      features that favor the diagnosis of primary lung adenocarcinoma (acini, lepidic
      growth, nuclear pseudoinclusions, and scar) or metastatic breast carcinoma
      (comedonecrosis, solid nests, trabecular architecture, and cribriform growth) was
      identified. The external validity of this model was successfully tested by
      challenging 19 pathologists and trainees with a test set of 20 unknown FSs,
      supporting the clinical applicability of the diagnostic model.

PMID- 19095576
TI  - Primary pulmonary adenocarcinoma with intestinal differentiation mimicking
      metastatic colorectal carcinoma: case report and review of literature.
AB  - Pulmonary adenocarcinoma with intestinal differentiation is rare and typically
      expresses proteins common to lung primaries. We report a case in a 51-year-old
      woman with a solitary 3.3-cm mass in the left lower lobe. Additional clinical
      investigation, including positron emission tomography scan with fluorine 18
      labeled fluorodeoxyglucose, colonoscopy, and capsule endoscopy of her small
      bowel, revealed no evidence of tumor elsewhere. She underwent left lower
      lobectomy with mediastinal lymphadenectomy. Histologic examination revealed tall
      columnar cells without goblet cell differentiation arranged in a cribriform and
      acinar pattern with extensive central necrosis. Metastatic carcinoma was present
      in multiple hilar lymph nodes. Mediastinal lymph nodes were negative.
      Immunohistochemical stains demonstrated diffuse positivity for cytokeratin (CK)
      20 and CDX-2 in neoplastic cells with negative staining for CK7 and thyroid
      transcription factor-1. CK7 expression has been documented in all 14 cases
      previously reported. This is the first description of pulmonary adenocarcinoma
      with intestinal differentiation with histopathologic and immunophenotypic
      findings indistinguishable from metastatic colorectal adenocarcinoma.

PMID- 19095577
TI  - Cribriform-morular variant of papillary thyroid carcinoma: molecular
      characterization of a case with neuroendocrine differentiation and aggressive
      behavior.
AB  - We describe an especially aggressive case of cribriform-morular variant (C-MV) of
      papillary thyroid carcinoma (PTC) in a 42-year-old man with familial adenomatous
      polyposis who died with lung and brain metastases 17 months after thyroidectomy.
      The angioinvasive neoplasm combined a mixture of trabecular, solid, cribriform,
      and follicular patterns of growth with CD10+ morules. Follicles were devoid of
      colloid, and the nuclear features typical of PTC were present in some areas and
      missing in others. Tumor cells were positive for thyroid transcription factor-1
      and, in 40% of the tumoral mass, also were positive for chromogranin and
      synaptophysin and were negative for thyroglobulin and calcitonin. Strong nuclear
      staining for beta-catenin was found in all tumor cells, as was positivity for p53
      and cyclin D1. In addition to the germline heterozygous APC Ex 2-3 duplication
      mutation, a somatic homozygous silent p. Thr1493Thr gene variant was found in the
      neoplastic cells along with RET/PTC rearrangement. This tumor represents the
      first case of C-MV of PTC showing neuroendocrine differentiation.

PMID- 19095578
TI  - Overweight and obesity among adults in Poland, 1983-2005.
AB  - INTRODUCTION: Overweight and obesity are causes for numerous non-communicable
      chronic diseases. In recent years their incidence have become a major
      epidemiological problem both in Poland and many other countries. PURPOSE:
      Evaluation of the current situation of the overweight and obesity prevalence
      among adults in Poland and changes in this regard in the years 1983-2005.
      MATERIAL AND METHODS: Review of the countrywide research and research in selected
      towns and regions on overweight and obesity occurrence conducted in Poland over
      the last 20 years. RESULTS: On the basis of national data for Poland, the
      incidence of overweight is estimated to be 39-40% among men and 28-29% among
      women, while the percentage of obese men and women is 16-21% and 19-22%
      respectively. The incidence of overweight and obesity differs with respect to
      gender, age, environment, the region of the country and social status. Excessive
      body weight is often observed in patients treated in hospitals. Abdominal obesity
      is very common and according to the ATP III guidelines, affects 16-28% of men and
      35-40% of women, whereas under more strict IDF criteria it involves almost 40% of
      adult males and almost a half of adult females. CONCLUSIONS: Results from
      numerous surveys conducted in the last few years indicate growth of the incidence
      of overweight and obesity, especially among men. The prevalence of overweight and
      obesity in Poland is comparable with most European countries.

PMID- 19095579
TI  - Quantification of the mRNA encoding Tumor Necrosis Factor alpha (TNFalpha) and
      its receptors in human nasal polyps.
AB  - PURPOSE: The object of the study was to assess the expression of the genes
      encoding TNFalpha and its receptors (TNF-R1 and TNF-R2) in patients with nasal
      polyps (NP). MATERIAL AND METHODS: The number of the mRNA copies was assessed by
      QRT-PCR in RNA extracts from 16 eosinophilic (ENP) and 5 neutrophilic nasal
      polyps (NNP), and 9 normal mucosa (NM) samples. The expression of corresponding
      proteins was demonstrated using immunohistochemistry. RESULTS: The mean level of
      mRNA copies for TNFalpha in ENP (82229c/microg) was not significantly higher when
      compared with controls (74869c/microg). NNP demonstrated significantly lower mean
      TNFalpha gene expression (7021c/microg) than the controls (p<0.05). A
      statistically higher mRNA TNFalpha copy number in ENP than in NNP was also
      revealed (p<0.01). A noticeably lower mRNA expression of TNF-R1 in ENP and NNP
      was seen as compared to the control group (10198c/microg vs. 30749c/microg,
      p<0.05 and 3440c/microg vs. 30749c/microg; p<0.05 respectively). In ENP the mean
      TNF-R2 mRNA copy number was markedly higher than in NNP (185c/microg vs.
      7.6c/microg, p<0.05). TNF-R2 mRNA level did not differ significantly between ENP
      and the control group (185c/microg vs. 469c/microg). TNF-R1 expression was
      significantly higher than TNF-R2 at the mRNA (p<0.01) and protein (p<0.05) level
      both in ENP and NNP. No significant correlations in proteins expression were
      detected between ENP and NNP. CONCLUSIONS: TNF-R1 has been identified to be a
      prevalent form of the TNFalpha receptor in nasal polyps which may reflect the
      apparent dominance of this form in TNFalpha signalling. The findings raise the
      possibility that the eosinophils from NP may influence biological responses
      through TNFalpha-dependent mechanisms. The differences between ENP and NNP
      relating to TNFalpha and the expression of its receptors may reflect the distinct
      character of those diseases.

PMID- 19095580
TI  - Does variability in carotenoid composition and concentration in tissues of the
      breast and reproductive tract in women depend on type of lesion?
AB  - PURPOSE: Vitamin A takes part in many physiological and pathological processes in
      women's reproductive organs. The study objective was to compare the carotenoid
      content in benign and malignant lesions of the breast, ovary and uterus, and to
      demonstrate quantitative and qualitative similarities or differences between the
      study groups. MATERIALS AND METHODS: Materials for analysis were physiological
      and pathological tissues of breast, ovary and uterus. The carotenoid pigments
      were isolated using column chromatography (CC), thin-layer chromatography (TLC)
      and high-performance liquid chromatography (HPLC). RESULTS: Sixteen carotenoids
      were identified in the study material, including those belonging to the
      provitamin A group. The most common were: beta-carotene, beta-cryptoxanthin,
      lutein, mutatoxanthin, violaxanthin, lutein epoxide and zeaxanthin. All the
      tissues subjected to analysis contained beta-carotene, 98% of the tissues had
      beta-cryptoxanthin, whereas alpha-carotene was detected in about 50% of breast
      tissue. No differences in carotenoid concentration were found between benign and
      malignant lesions in the examined tissues, apart from hydroxyechinenone,
      canthaxanthin, astaxanthin, lutein epoxide, antheraxanthin and neoxanthin.
      Similarly, no differences in concentration of the provitamin A carotenoids (alpha
      carotene, beta-carotene, beta-cryptoxanthin, and echinenone) were found between
      benign and malignant lesions except hydroxyechinenone. The highest total content
      of carotenoids and the biggest spectrum of predominant carotenoids were found in
      the breast. Only in tissues of malignant lesions of the uterus, we observed
      statistically higher total content of carotenoids compared to remaining samples
      from the uterus (p<0.001) and more frequent isolation of some carotenoids
      (compared to benign lesions). CONCLUSION: The results of our study confirmed the
      presence of a high diversity of carotenoids in the physiologic, benign and
      malignant tissues of the breast and the reproductive tract in women. The
      differences observed among the frequency of isolation of some carotenoids do not
      allow to make straightforward conclusions. The frequent isolation of provitamin A
      carotenoids in the examined material and the lack of their occurrence as major
      carotenoids may be connected with using them in the cellular biological
      processes. However, this requires further investigation.

PMID- 19095581
TI  - Acid gastroesophageal reflux and intensity of symptoms in children with
      gastroesophageal reflux disease. Comparison of primary gastroesophageal reflux
      and gastroesophageal reflux secondary to food allergy.
AB  - The ability to differentiate between primary and secondary causes of
      gastroesophageal reflux (GER) is extremely important during the diagnostic
      procedure. At the same time, the quality of symptoms and the intensity of the
      course of gastroesophageal reflux disease (GERD) should be estimated. Acid GER is
      assessed using 24-hour esophageal pH monitoring; the results of this diagnostic
      test should always be interpreted alongside the clinical picture. PURPOSE: To
      establish the interdependence between the intensity of the clinical symptoms and
      the acid reflux index in children with primary GER and GER secondary to cow's
      milk protein allergy (CMA) and/or other food allergies (FA). MATERIALS AND
      METHODS: A total of 138 children of various ages with symptoms of GERD were
      included in the study. The diagnostic procedure included 24-hour pH monitoring of
      the esophagus with a 2-channel probe (distal and proximal lead). For this
      purpose, ESPGAN diagnostic criteria were implemented. The type and intensity of
      typical manifestations of GERD were assessed with the help of our own scoring
      system. This diagnostic and therapeutic algorithm which includes an oral food
      challenge test, was applied to 138 children in order to differentiate primary GER
      from GER secondary to CMA/FA. RESULTS: Primary GERD was diagnosed in 76 patients
      (55.1%) with a mean age: x=25.20 months+/-27.28 (group 1) and GERD secondary to
      CMA/FA was confirmed in 62 children (44.9%) with a mean age: x=21.53 months+/
      17.79 (group 2). The most important pH-metric parameter analyzed in study groups
      1 and 2 was the GER index: total and supine. An assessment of the intensity of
      symptoms and a comparative analysis of intensity was evaluated against the GER
      index: total and supine. Among study group 1, the following gradation of symptoms
      was found: in 31 children (40.8%)-degree 3, in 33 children (43.4%)-degree 4, and
      in 12 children (15.8%)-degree 5, whereas among the patients in group 2:25 (40.3%)
      were in degree 3, 27 (43.6%) were in degree 4, and 10 (16.1%) were in degree 5.
      It was estimated that the higher the GER result in both total and supine
      positions (for both leads), the higher the level of symptoms noted. This
      interdependence was demonstrated for both groups. CONCLUSIONS: In seeking to
      determine any etiopathogenetic connection between primary GER or GER secondary to
      CMA/FA and their clinical consequences, 24-hour esophageal pH monitoring with a 2
      channel probe is recommended, since it provides for better clinical control of
      GERD and its appropriate treatment.

PMID- 19095582
TI  - The effect of mastication on occlusal parameters in healthy volunteers.
AB  - PURPOSE: To assess possible associations between occlusal parameters and
      comminution of solid food during chewing in a group of completely dentate
      subjects. MATERIALS AND METHODS: Twenty-five completely dentate volunteers (28
      teeth, 14 functional dental units) aged 24-50 yrs, without any complaints of the
      stomatognathic system participated in this study. An Optosil test was used to
      estimate masticatory efficiency for 20 and 80 cycles of chewing. An occlusal
      analysis, using the T-Scan II System, was performed to assess the following
      occlusal parameters: the distribution of occlusal contacts, the time of
      occlusion, the chewing platform area before chewing and after 20 and 80 cycles of
      chewing. RESULTS: The parameters, that were taken into account: i. X50 for 20 and
      80 cycles of chewing, ii. the occlusion time, iii. the occlusal contact area. The
      occlusion time decreased after 20 and 80 chewing cycles (mean TO0=0.28+/-0.07 vs
      TO20=0.21+/-0.05 s vs TO80=0.18+/-0.05 s, respectively). The mean value of the
      chewing platform area was 125.12+/-46.5 mm2. CONCLUSION: Prolongation of chewing
      produces, shortening of the occlusion time while the chewing platform area
      remains at the same level independent of the number of chewing cycles.

PMID- 19095583
TI  - Annual variations of quantitative EEG in patients with chronic epilepsy.
AB  - PURPOSE: Annual changes in powers of the close-eyed EEG were measured over 12
      months in 12 patients with epilepsy. MATERIAL AND METHODS: The present study
      included 12 patients aged 14.6+/-2.7 years with chronic epilepsy, suffering for 6
      14 years. EEGs were recorded every month between 9 and 11 a.m. Five patients had
      generalized seizures and 7 partial complex seizures secondarily generalized.
      Visual analysis of EEG was performed before the quantitative assessment. The
      signals were recorded using a set of 14 (F3, F4, F7, F8, C3, C4, P3, P4, 01, 02,
      T3, T4, T5, T6) scalp electrodes. For each patient, 20 artifact-free EEG epochs,
      each of 2 s. duration were selected for spectral analysis to calculate spectral
      power. The sampling frequency was 240 Hz. Frequencies below 1 Hz and above 70 Hz
      were eliminated by digital filtering. The channels were recorded relative to a
      vertex reference. A fast Fourier transformation algorithm of signal processing
      was used to obtain the power spectrum of each lead. Absolute power spectrum was
      calculated within 4 frequency bands: delta (1-3.99 Hz), theta (4-7.99 Hz), alpha
      (8-12.99 Hz), and beta (13-30.99 Hz). RESULTS: We found the abnormalities to be
      predominantly focal in EEG. None of the EEG recordings were normal, and the power
      spectra differed over the year. A statistically significant increase of delta and
      theta bands in May and a decrease of alpha bands in September was found. We did
      not find positive correlations between the changes in the quantitative EEG
      analysis and the number of seizures in patients. CONCLUSIONS: These findings
      suggest the annual variations of EEG in patients with chronic epilepsy.
      Furthermore studies are needed to clarify the annual variations of EEG among
      healthy volunteers.

PMID- 19095584
TI  - Chosen IL-17 family proteins in neutrophils of patients with oral inflammation.
AB  - PURPOSE: Recent studies have indicated that human neutrophils (PMN), belonging to
      the first line of cellular defence against various infectious agents and
      inflammation can produce cytokines of the interleukin 17 (IL-17) family. The
      relation between pro-inflammatory IL-17A and anti-inflammatory IL-17E may be
      responsible for the development and maintenance of the inflammatory process. The
      study objective was to determine the expression of IL-17E and IL-17BR in
      confrontation with IL-17A and IL-17R in neutrophils of patients with oral cavity
      inflammation and to compare protein expressions in autologous peripheral blood
      mononuclear cells (PBMC). MATERIAL AND METHODS: Expressions of IL-17E, IL-17A, IL
      17BR and IL-17R was assessed by the Western blot method. IL-17E and IL-17A levels
      was determined by the ELISA method. RESULTS: The expressions of IL-17E, IL-17A,
      IL-17BR and IL-17R in PMN and PBMC in patients were higher in the cells of
      patients, as compared to the controls. The expressions of IL-17E and IL-17BR in
      both kinds of cells were lower than the levels of IL-17A and IL-17R. The levels
      of IL-17E and IL-17A were increased in cell supernatants and blood serum of
      patients, as compared to the control group. CONCLUSIONS: The preliminary
      examinations indicate the predominance of pro-inflammatory effects of IL-17A
      controlled by PMN, as well as PBMC in patients with oral inflammation. Results
      obtained also suggest a more significant involvement of PMN in the IL-17E and IL
      17A dependent reactions.

PMID- 19095585
TI  - Editor's foreword.

PMID- 19095586
TI  - "One day I might find myself HIV-positive like her": audience involvement and
      identification with role models in an entertainment-education radio drama in
      Botswana.
AB  - Entertainment-education programs promote health and development goals throughout
      the world. This study looks specifically at a radio serial drama designed to
      provide behavioral role models for HIV prevention and reproductive health in
      Botswana as part of the behavior-change strategy, Modeling and Reinforcement to
      Combat HIV/AIDS (MARCH). The purpose of this qualitative study is to elucidate
      regular listeners' involvement and identification with three different types of
      fictional characters in the drama. Regular listeners were interviewed using a
      semi-structured guide; 31 interviews were analyzed to assess respondents'
      reactions to three female characters. The findings suggest that characters
      designed to be "negative," "positive," and "transitional" (i.e., moving from
      negative to positive) role models were generally perceived as such and that the
      type of behavior modeled influenced whether a character was perceived to be
      transitional or positive. Audience members discussed the implications of specific
      behaviors by contrasting the different character types. Although characters
      modeled behaviors within distinct but interrelated storylines, the respondents
      spontaneously compared characters' ways of confronting similar dilemmas across
      storylines, suggesting that listeners perceived the drama as a unified whole
      rather than as a series of parallel stories. The use of more than one
      transitional character for each behavioral objective might be beneficial for
      improving audience identification with agents of behavior change by providing
      several models to which the audience can relate.

PMID- 19095588
TI  - Clean hands: prevention of typhoid fever in rural communities in Egypt.
AB  - Typhoid fever is a serious public health problem in Egypt. Effective prevention
      strategies include the promotion of handwashing. This study explores factors that
      influence handwashing practices in the Egyptian setting and makes recommendations
      on how to use this information in a handwashing campaign. In addition to key
      informant interviews, 16 focus group discussions and 21 in-depth interviews were
      carried out with female respondents in three different rural sites. The data was
      analyzed by using content analysis technique. The findings showed that the
      concept of dirt (microbaat and talaus) influences hygiene behavior as it relates
      to the outside (i.e., real and visible things). The respondents have low risk
      perceptions related to typhoid fever and they do not conceptualize long disease
      transmission chains. The scarcity of water and problems with disposal of waste
      water hinder handwashing. These findings were incorporated into a pilot campaign
      to promote handwashing using strategies that included the visualization of germs
      in critical areas during critical times, discussions of germ theory, and
      encouragement to solve environmental and infrastructural constraints that hinder
      handwashing practices at the household level.

PMID- 19095587
TI  - "My mother told me I must not cook anymore"--food, culture, and the context of
      HIV- and AIDS-related stigma in three communities in South Africa.
AB  - The purpose of this study was to examine the role of food as an instrument in
      expressing and experiencing HIV/AIDS stigma by HIV-positive women and their
      families, with the goal of reducing discrimination. It goes beyond willingness to
      share utensils, which has been identified in HIV/AIDS research. As part of an
      ongoing capacity-building HIV/AIDS stigma project in South Africa, 25 focus
      groups and 15 key informant interviews were conducted among 195 women and 54 men
      in three Black communities. Participants were asked to discuss how they were
      treated in the family as women living with HIV and AIDS, and data was organized
      using the PEN-3 model. Findings highlight both the positive and negative
      experiences HIV-positive women encounter. Women would not disclose their HIV
      status to avoid being isolated from participating in the socio-cultural aspects
      of food preparation, while others that have disclosed their status have
      experienced alienation. The symbolic meanings of food should be a major
      consideration when addressing the elimination of HIV/AIDS stigma in South Africa.

PMID- 19095589
TI  - Reproductive health knowledge, sexual partners, contraceptive use and motives for
      premarital sex among female sub-urban Nigerian secondary students.
AB  - Adolescents in sub-Saharan African countries constitute a large proportion of the
      population. They are sexually active, engage in unsafe reproductive health
      behavior with attendant consequences but lack appropriate reproductive health
      education. In the Nigeria Nation Reproductive Health Strategy Framework and Plan,
      the status of adolescents' reproductive health care is considered low. This study
      assessed reproductive health knowledge, sexual partners, contraceptive use, and
      motives for premarital sex among female sub-urban Nigerian secondary students.
      The study was cross-sectional, involving 500 senior secondary 1 and 2 female sub
      urban students. The instrument used was a self-administered questionnaire. Data
      were analyzed using SPSS. More than 70.0% of the respondents had knowledge of all
      reproductive health items; male and female condoms were popular contraceptives.
      At least 53.4% were sexually active and a majority (49.6%) had boyfriends as sex
      partners. Peer pressure (31.6%) and fun/pleasure (29.2%) were major motives for
      engaging in premarital sex. Majority (40.3%) terminated pregnancies through self
      medication. Though respondents had knowledge of reproductive health, there is
      need to introduce health education (incorporating reproductive health education)
      as a core subject in schools as well as provision of youth-friendly health
      facilities.

PMID- 19095590
TI  - Addressing the health needs of the aged in the U.S.A.
AB  - The segment of the population consisting of those sixty-five years of age and
      older will continue to grow in both absolute and relative terms. The fastest rate
      of growth will occur among those in the oldest age brackets where there is a
      greater amount of disability. Certain health problems are associated with
      behavioral factors that are sometimes amenable to educational interventions. This
      paper discusses structural aspects of the health care system that make such
      intervention efforts more difficult. An incomplete array of health programs,
      inadequate benefits, and lack of suitable training for health professionals are
      among the items considered.

PMID- 19095591
TI  - How basic beliefs about human life relate to ethical judgments about induced
      abortion.
AB  - This survey explores family planning field workers' basic beliefs and value
      assessments related to a new human life and their relationship to their verbal
      statements of ethical judgments about induced abortion under varying
      circumstances in Taiwan. It also relates these beliefs to stated experience of
      abortion referrals. Implications for education and research with application to
      other countries and international social issues are discussed.

PMID- 19095594
TI  - Pheochromocytoma in patients suspected of harboring adrenal metastasis:
      management and clinical predictors.
AB  - OBJECTIVE: To study clinical management of patients with suspected adrenal
      metastasis and to assess whether there are clinical predictors of
      pheochromocytoma in this patient population. METHODS: In this retrospective cross
      sectional study, we reviewed medical records of patients who had adrenalectomy
      for adrenal lesions or had adrenal biopsy performed between January 1997 and July
      2007 in a large academic hospital. Patients who harbored adrenal masses that were
      suspected of being metastases were identified on clinical findings. Pathologic
      diagnosis, demographic data, clinical history, imaging studies, and laboratory
      test results were reviewed and compared among patients whose adrenal mass was
      determined to be metastasis, adenoma, or pheochromocytoma. RESULTS: One-hundred
      sixty-three patients had adrenalectomy or had adrenal biopsy during the study
      period. Thirty patients (18%) had adrenal masses that were suspected of being
      metastases. Of the adrenal masses, 18 (60%) were metastases, 8 (27%) were benign
      adenomas, and 4 (13%) were pheochromocytomas. Eleven patients (37%) had
      biochemical testing for pheochromocytoma. Adrenal biopsy was performed without
      biochemical testing for pheochromocytoma in 9 patients (30%), including 2
      subsequently found to have this tumor. Adrenalectomy was performed in 10 patients
      (33%) without biochemical testing for pheochromocytoma. Clinical parameters were
      similar among patients with metastasis, adenoma, or pheochromocytoma. There were
      no clinical predictors to suggest pheochromocytoma. CONCLUSIONS: Pheochromocytoma
      occurs frequently in patients suspected of harboring adrenal metastasis, but this
      tumor is often not considered in clinical practice. The size and imaging
      characteristics of the adrenal mass and history of known metastasis may help
      clinicians in decision-making. Biochemical testing for pheochromocytoma should
      ideally be performed in all patients suspected of having adrenal metastasis.

PMID- 19095593
TI  - Optimum recombinant human thyrotropin dose in patients with differentiated
      thyroid carcinoma and end-stage renal disease.
AB  - OBJECTIVE: To evaluate serum thyrotropin (TSH) concentrations after conventional
      (0.9 mg) or half-dose (0.45 mg) administration of recombinant human TSH (rhTSH)
      injections intramuscularly in patients with end-stage renal disease and
      differentiated thyroid cancer. METHODS: In this case series, we administered 2
      doses of 0.9-mg rhTSH or 2 doses of 0.45-mg rhTSH to 3 patients with renal
      failure and differentiated thyroid cancer who were receiving hemodialysis. Basal
      serum TSH concentrations were assessed while the patients were taking thyroid
      hormone therapy. Serum TSH was measured on days 2, 3, 5, 8, 10, 14, and 17 of the
      study. Thyroglobulin and thyroglobulin antibodies were also measured on days 5
      and 7. Patients were asked to report any adverse effects. RESULTS: Patient 1, who
      received 2 injections of 0.9-mg rhTSH administered on days 1 and 3, had
      persistently elevated serum TSH levels for approximately 11 days. Peak serum TSH
      measured on day 5 was 644 mIU/L. Self-limited diarrhea was the only reported
      adverse effect. Patients 2 and 3 received 0.45 mg of rhTSH on 2 consecutive days
      (days 1 and 2), and both exhibited persistently elevated serum TSH levels for 12
      days. The peak serum TSH values on day 3 were 402 mIU/L in Patient 2 and 386
      mIU/L in Patient 3. No adverse events were observed in these 2 patients. Patient
      2 received thyrotropin alfa for injection to confirm disease status. Patient 3
      also received a radioiodine dose because of presumed persistent disease.
      CONCLUSION: High serum TSH levels achieved after conventional and half-dose
      administration of rhTSH suggest that a dose adjustment might be considered in
      patients with end-stage renal disease.

PMID- 19095595
TI  - Changes in body composition in women following treatment of overt and subclinical
      hyperthyroidism.
AB  - OBJECTIVE: To determine changes in weight, body composition, and bone density
      after treatment of overt hyperthyroidism (OH) and subclinical hyperthyroidism
      (SCH) in women. METHODS: Women with OH and SCH referred to the Mayo Clinic
      Thyroid Clinic were recruited. Hyperthyroid patients and euthyroid control women
      were matched for age (within decade) and body mass index. Patients with OH and
      SCH were treated to normalize thyroid function test results and were restudied
      after 6 months of normal thyroid function. Baseline and posttreatment studies
      included measurement of height, weight, bone density, lean mass, fat mass, and
      thigh muscle cross-sectional area. All participants had normal thyroid function
      test results for at least 6 months before completion of the posttreatment
      studies. RESULTS: Twenty-four patients with OH, 21 patients with SCH, and 36
      control patients were studied. In the OH group, fat-free mass increased from a
      mean of 36.8 kg (95% confidence interval [CI], 34.8-38.8) to 40.4 kg (95% CI,
      38.5-42.3); in the SCH group, fat-free mass increased from a mean of 40.3 kg (95%
      CI, 38.1-42.5) to 42.2 kg (95% CI, 39.7-44.7). In both groups, fat mass increased
      to approximately the same extent, and both groups experienced significant weight
      gain with no change in percent body fat. Thigh muscle cross-sectional area
      increased in both groups -- from 100.6 cm(2) (95% CI, 92.7-108.5) to 113.3 cm(2)
      (95% CI, 105.5-121.1) in the OH group and from 106.1 cm(2) (95% CI, 96.7-115.5)
      to 112.2 cm(2) (95% CI, 102.0-122.4) in the SCH group. Bone density increased in
      patients with OH (P<.01) and in patients with SCH (P<.05). CONCLUSIONS: Treatment
      of OH and SCH leads to increases in muscle area and bone density. Weight gain
      reflects increases in both fat and fat-free mass. While these results provide
      some support for actively treating SCH in women, further prospective studies are
      needed to determine whether the changes documented translate into real patient
      benefit.

PMID- 19095596
TI  - Effectiveness and long-term safety of thiazolidinediones and metformin in renal
      transplant recipients.
AB  - OBJECTIVE: To investigate the long-term safety and effectiveness of
      thiazolidinediones and metformin in renal transplant recipients with
      posttransplant diabetes mellitus (PTDM) or preexisting diabetes mellitus (DM).
      METHODS: Retrospective chart review was performed for renal transplant recipients
      with PTDM or preexisting DM followed up during the years 2000-2006. Data
      collected included baseline characteristics; glomerular filtration rate (GFR);
      creatinine; hemoglobin A1c; and development of congestive heart failure, edema,
      and liver function abnormalities. GFR was calculated using the Modification of
      Diet in Renal Disease study equation calculator. RESULTS: Thirty-two patients
      comprised the metformin group (PTDM = 21, preexisting DM = 11), and 46 patients
      were included in the TZD group (PTDM = 33, preexisting DM = 13). Only 24 patients
      taking metformin and 31 patients taking TZDs were included for effectiveness
      analysis since the others required additional medications to control their DM.
      Mean follow-up was 16.4 months (range, 1-55 months) for patients treated with
      metformin and 37.1 months (range, 6-72 months) for patients treated with TZDs.
      GFR was decreased from baseline in all patients, but the only significant change
      was in patients with preexisting DM. While there was a significant change in
      creatinine levels in the metformin group, only 5 patients had to discontinue the
      drug because of this elevation (3 in preexisting DM group, 2 in PTDM group).
      Change in hemoglobin A1c from baseline was not significant in either study group.
      Development of congestive heart failure or liver function abnormalities was not
      observed. CONCLUSIONS: Metformin appears to be safe in the renal transplant
      population for a mean duration of 16 months, although caution should be exercised
      using close monitoring in patients with preexisting DM. TZDs appear to be safe
      for a mean duration of 37 months after renal transplant.

PMID- 19095597
TI  - Effect of spironolactone therapy on albuminuria in patients with type 2 diabetes
      treated with angiotensin-converting enzyme inhibitors.
AB  - OBJECTIVE: To investigate whether the addition of spironolactone to angiotensin
      converting enzyme (ACE) inhibitors further decreases albuminuria in patients with
      type 2 diabetes mellitus (DM). METHODS: We conducted a prospective open-label
      trial in patients recruited at the Cleveland Clinic between February 2004 and
      November 2006. Patients with type 2 DM were eligible if they were older than 18
      years of age, had been treated with any ACE inhibitor for longer than 1 month,
      and had a random urinary albumin to creatinine ratio (ACR) greater than 100 mg/g
      within 1 month of study entry. Based on screening ACR, patients were assigned to
      a microalbuminuria group (ACR 100-300 mg/g) or a macroalbuminuria group (ACR >300
      mg/g). Patients were followed up for 12 weeks, with 4 clinic visits, 4 weeks
      apart. At visit 2, spironolactone, 25 mg once daily, was initiated and continued
      for 4 weeks. At visit 3, spironolactone was discontinued. Clinical information
      was obtained at each visit as were serum chemistries and 24-hour urinary albumin
      excretion. RESULTS: Twenty-four patients with type 2 DM and albuminuria completed
      the study. Eleven patients had microalbuminuria and 13 had macroalbuminuria.
      Following treatment with spironolactone, urinary albumin excretion dropped from a
      mean +/- SD of 404.6 +/- 60.9 mg/d to 302.7 +/- 52.7 mg/d (25.7% decrease,
      P<.001). In the microalbuminuria and macroalbuminuria groups, the urinary albumin
      excretion dropped 27.2% (P = .05) and 24.3% (P = .02), respectively. Despite a
      significant decrease in systolic blood pressure between visits 2 and 3 (141.2 +/-
      3.5 to 132.5 +/- 3.6 mm Hg; P = .002), this change did not correlate to the
      change in albuminuria (r(2) = 0.02; P = .23). There were no withdrawals due to
      hyperkalemia. CONCLUSION: Spironolactone is effective in further decreasing
      albuminuria in patients with type 2 DM who are already treated with ACE
      inhibitors.

PMID- 19095598
TI  - Exenatide use in the management of metabolic syndrome: a retrospective database
      study.
AB  - OBJECTIVE: To evaluate the effect of exenatide therapy on cardiometabolic risk
      factors and anthropometric parameters in patients with metabolic syndrome.
      METHODS: From June 2005 to June 2007, we performed a retrospective analysis of
      data extracted from the records of adult patients with metabolic syndrome being
      treated with exenatide. Diagnosis of any type of diabetes mellitus was
      exclusionary. Patients were initiated on exenatide therapy, 5 mcg, 1 hour before
      their morning and evening meals for the first month and were instructed to
      titrate up to 10 mcg. Cardiometabolic risk factors (total cholesterol, high
      density lipoprotein cholesterol, triglycerides, calculated low-density
      lipoprotein cholesterol, and blood pressure) and anthropometric parameters
      (absolute body weight, body mass index, and abdominal girth) were measured at
      baseline and at 16 +/- 4 weeks after initiating exenatide therapy. Data collected
      also included age, sex, metabolic syndrome diagnosis, and other concomitant
      medication used in the management of endocrine disorders. RESULTS: The study
      population consisted of 299 patients (259 women, 40 men) with an age range of 18
      to 74 years. Exenatide treatment was associated with significant reductions in
      mean body weight (P<.001) and body mass index (P<.001). Weight loss in 76.6% of
      patients was concomitant with a significant reduction in mean abdominal girth
      (P<.001). Further analysis revealed significant decreases in mean triglycerides
      (P<.001), total cholesterol (P<.01), and both systolic (P<.01) and diastolic
      blood pressure (P<.03). Approximately 60.2% of patients used metformin
      concomitantly, and half either decreased or discontinued metformin therapy.
      CONCLUSIONS: This is the first report examining the effect of exenatide on
      patients with metabolic syndrome. We observed a significant improvement in
      cardiometabolic risk factors and anthropometric parameters as a result of
      exenatide over the treatment interval.

PMID- 19095599
TI  - Relationship of prostate-specific antigen to age and testosterone in men with
      type 2 diabetes mellitus.
AB  - OBJECTIVE: To determine whether prostate-specific antigen (PSA) concentrations in
      type 2 diabetic men with hypogonadotrophic hypogonadism are lower than those in
      eugonadal men with type 2 diabetes and whether PSA concentrations are related to
      plasma testosterone concentrations. METHODS: In this cross-sectional study, we
      measured serum total testosterone, sex hormone-binding globulin, free
      testosterone, PSA, hematocrit, and hemoglobin A1c in consecutive type 2 diabetic
      men who presented to 2 endocrinology referral centers between January 2006 and
      January 2007. We collected other clinical and demographic data including age,
      height, weight, and ethnicity. RESULTS: Of 400 eligible patients, 280 men met
      inclusion criteria. Plasma PSA concentrations were lower in type 2 diabetic men
      with low free testosterone concentrations than in those with normal free
      testosterone concentrations (0.89 +/- 0.07 ng/mL vs 1.10 +/- 0.08 ng/mL,
      [corrected] P = .011). PSA concentrations were positively related to age (r =
      0.34, P<.001), total testosterone (r = 0.29, P<.001), free testosterone (r =
      0.17, P = .02), and sex hormone-binding globulin (r = 0.22, P<.001) and
      negatively related to body mass index (r = -0.28, P<.001). In stepwise backward
      regression analysis, PSA concentration was predicted by age (P<.001) and free
      testosterone (P<.001), but not by body mass index or sex hormone-binding
      globulin. CONCLUSIONS: Plasma PSA concentrations are lower in type 2 diabetic men
      with hypogonadism than in eugonadal men with type 2 diabetes, and plasma PSA is
      related to age, plasma total testosterone concentrations, and free testosterone
      concentrations in patients with type 2 diabetes.

PMID- 19095600
TI  - Insulin immunoassays in the detection of insulin analogues in factitious
      hypoglycemia.
AB  - OBJECTIVE: To report a case of surreptitious insulin use and to review the
      differences in insulin assays and how they may be optimally used in testing for
      factitious hypoglycemia. METHODS: We describe the clinical, physical, and
      laboratory findings of the study patient and review the current relevant
      literature regarding surreptitious insulin use and detection by insulin assays.
      RESULTS: A 36-year-old man with type 1 diabetes mellitus was admitted to the
      hospital with a serum glucose concentration of 28 mg/dL. He reported taking very
      small amounts of glargine and aspart insulin (16 units per day). Mitigating
      endocrine causes of hypoglycemia (eg, adrenal insufficiency) were investigated
      and excluded. His serum insulin concentration was 14 microIU/mL (reference range,
      3-25 microIU/mL) despite his statement that he was not taking human insulin.
      Serum insulin concentration steadily decreased over the hospital course. The
      declining insulin levels, coupled with resolution of hypoglycemia, suggested the
      abuse of human insulin. After confrontation with this evidence, he was referred
      to psychiatric services. Evaluation of surreptitious human insulin use is
      straightforward since it can be distinguished from endogenous insulin excess (eg,
      insulinoma) by existing assays for insulin, C-peptide, and proinsulin. However,
      the increasing use of insulin analogues in lieu of human insulin has made such
      evaluations more difficult because commercially available insulin assays detect
      these synthetic insulins with varying sensitivity. CONCLUSIONS: Factitious
      insulin use remains an uncommon yet hazardous problem. Human insulin is readily
      available without a prescription, providing easy access to an extremely dangerous
      substance. Understanding the specific detection abilities of each assay is
      essential to the evaluation of factitious insulin-induced hypoglycemia.

PMID- 19095601
TI  - Vitamin D-mediated hypercalcemia and Cushing syndrome as manifestations of
      malignant pleural mesothelioma.
AB  - OBJECTIVE: To report a case of coincident hypercalcemia and Cushing syndrome
      arising from mesothelioma. METHODS: We describe the clinical, laboratory,
      imaging, and pathologic findings of a patient with malignant pleural mesothelioma
      and elucidate the underlying biologic mechanisms resulting in concurrent
      overexpression of steroid and polypeptide hormones. RESULTS: A 62-year-old woman
      presented with chest discomfort and cough. Radiologic imaging revealed a diffuse
      pleural-based mass encasing the right lung. There was no invasion into the chest
      wall, diaphragm, or mediastinum, and there was no distant disease. Laboratory
      analyses documented hypercalcemia and Cushing syndrome, which were due to ectopic
      overproduction of 1,25-dihydroxyvitamin D (1,25[OH](2)D) and corticotropin.
      Surgical resection resulted in normocalcemia with normalization of serum
      1,25(OH)(2)D and reduction in hypercortisolemia. The extrapleural pneumonectomy
      specimen revealed overexpression of the 1,25(OH)(2)D synthetic enzyme 25
      hydroxyvitamin-D-1alpha-hydroxylase (1alpha-hydroxylase) and underexpression of
      the 1,25(OH)(2)D catabolic enzyme 24-hydroxylase. Immunohistochemistry and
      electron microscopy demonstrated corticotropin and secretory granules in the
      tumor tissue. CONCLUSION: These findings support the evidence for a paracrine
      role of vitamin D in the resistance of the human host to antigen.

PMID- 19095602
TI  - Severe hyponatremia due to rosiglitazone use in an elderly woman with diabetes
      mellitus: a rare cause of syndrome of inappropriate antidiuretic hormone
      secretion.
AB  - OBJECTIVE: To describe the first case of syndrome of inappropriate antidiuretic
      hormone secretion with life-threatening hyponatremia due to rosiglitazone
      therapy. METHODS: We describe the clinical, laboratory, and imaging findings of
      the study patient. RESULTS: An 89-year-old woman with a 5-year history of type 2
      diabetes mellitus was admitted to the emergency department because of
      unconsciousness. She had reported generalized weakness for 15 days and nausea and
      vomiting for 3 days. Findings from laboratory analysis showed severe hyponatremia
      (sodium, 110 mEq/L). She had normal renal, cardiac, and adrenal function, and she
      did not have edema or volume depletion. The cause of hyponatremia was syndrome of
      inappropriate antidiuretic hormone secretion. We did not find any cause for her
      condition other than rosiglitazone, an antihyperglycemic drug that is
      increasingly being used in patients with type 2 diabetes mellitus. According to
      her medical history, rosiglitazone was prescribed 1 month previously after
      withdrawal of gliclazide. We stopped the rosiglitazone and administered
      hypertonic saline infusion to treat the hyponatremia. Saline infusion was stopped
      and blood sodium levels were stabilized in the normal range after 2 days. The
      patient's plasma sodium concentration has remained in the reference range at
      follow-up visits. CONCLUSIONS: This is the first reported case of syndrome of
      inappropriate antidiuretic hormone secretion as an adverse effect of
      rosiglitazone, and this drug should possibly be considered for addition to the
      list of drugs that cause this condition.

PMID- 19095603
TI  - A case of severe neuropathy associated with hypertriglyceridemia.
AB  - OBJECTIVE: To describe a case of severe neuropathy associated with
      hypertriglyceridemia. METHODS: We describe the clinical and laboratory findings
      of the study patient and review the relevant literature. RESULTS: A 45-year-old
      woman presented to the emergency department with recurrent abdominal pain and
      severe peripheral neuropathy. Her laboratory data revealed elevated lipase and a
      very high triglyceride concentration (>10,000 mg/dL), consistent with a diagnosis
      of recurrent hypertriglyceridemia-induced pancreatitis. Workup for peripheral
      neuropathy showed normal concentrations of thyrotropin, fasting blood glucose,
      vitamin B(12), and creatinine, as well as a normal hemoglobin A(1c) level, serum
      protein electrophoresis, and urine protein electrophoresis. Rapid plasma reagin
      antibodies, antinuclear antibodies, and lyme antibodies were not detected. In the
      absence of other identifiable causes, hypertriglyceridemia was deemed the likely
      etiology of severe neuropathy in this patient. CONCLUSIONS: Peripheral nerve
      conduction abnormalities can be identified in patients with mild
      hypertriglyceridemia in the absence of symptoms. Early recognition and aggressive
      management of hypertriglyceridemia may prevent the complications of severe
      peripheral neuropathy.

PMID- 19095604
TI  - Rhabdomyolysis after withdrawal of thyroid hormone in a patient with papillary
      thyroid cancer.
AB  - OBJECTIVE: To report a case of rhabdomyolysis presenting with severe hyperkalemia
      after withdrawal of thyroid hormone in a patient with differentiated thyroid
      cancer. METHODS: We describe the clinical and laboratory findings of the study
      patient and review the relevant literature. RESULTS: A 54-year-old man with
      progressive generalized weakness and myalgias presented with acute renal failure
      and hyperkalemia. He had undergone total thyroidectomy for papillary thyroid
      cancer 6 weeks earlier and had discontinued thyroid hormone 2 weeks before his
      current presentation in preparation for thyroid remnant ablation. He had a
      history of multiple colon and small-bowel resections for familial adenomatous
      polyposis and desmoid tumor. He was severely dehydrated on examination.
      Laboratory tests results included the following values: creatine phosphokinase,
      5265 U/L (reference range, 52-336 U/L); creatinine, 2.1 mg/dL; potassium, >8.0
      mEq/L; and thyrotropin, 92.2 mIU/L. His condition was diagnosed as
      rhabdomyolysis, and his fluid deficit and hyperkalemia were treated aggressively.
      Cardiac status remained stable, and both acute renal failure and hyperkalemia
      improved. He then received remnant ablation, and thyroid hormone was restarted.
      His muscle complaints resolved over the following 3 months. CONCLUSIONS:
      Hypothyroidism-induced rhabdomyolysis can occur during thyroid hormone withdrawal
      and can present with life-threatening hyperkalemia. Patients under-going thyroid
      hormone withdrawal should be assessed for risk of rhabdomyolysis, and preventive
      strategies should be implemented, including prevention of dehydration. The use of
      recombinant thyrotropin, rather than thyroid hormone withdrawal, should be
      considered in those who are at high risk for such complications.

PMID- 19095605
TI  - Sexual precocity in a 2-year-old boy caused by indirect exposure to testosterone
      cream.
AB  - OBJECTIVE: To report a rare case of sexual precocity caused by inadvertent
      exposure to testosterone cream. METHODS: We report the clinical, laboratory, and
      radiologic findings of a boy presenting with sexual precocity; review short- and
      long-term consequences; and discuss preventative measures. RESULTS: A 2 and 7/12
      year-old boy had onset of pubic hair without testicular enlargement and a period
      of rapid linear growth. History revealed possible topical testosterone exposure
      from close contact with the child's father. On physical examination, the boy had
      Tanner stage II pubic hair distribution. Laboratory evaluation findings were
      normal for age except for the testosterone concentration, which was comparable to
      late-pubertal and adult male levels at 371 ng/dL (reference range, <3-10 ng/dL
      for prepubertal male). Brain magnetic resonance imaging and testicular
      ultrasonography were normal. Skeletal age was advanced at age 4 and 6/12 years.
      Repeated laboratory evaluation, after the child's father ceased testosterone use,
      revealed a normal testosterone concentration of 10 ng/dL. Thus, this boy's sexual
      precocity was attributed to inadvertent exogenous androgen exposure. CONCLUSIONS:
      When examining a child with sexual precocity, asking about possible exposure to
      androgens and estrogens is important. Patients being treated with these products
      should be educated about the possible risks of testosterone exposure to others
      and ways to limit exposure.

PMID- 19095606
TI  - Hypertension and diabetes: a toxic combination.
AB  - OBJECTIVE: To assess the relationship of diabetes and hypertension and the effect
      on cardiovascular outcomes. METHODS: A review of the English-language literature
      regarding the effects of diabetes and hypertension published between January 1,
      1980, and April 30, 2008, was performed. RESULTS: In type 2 diabetes, the
      prevalence of hypertension due to both hyperglycemia and insulin resistance is
      increased. High insulin levels are associated with left ventricular hypertrophy
      and decreased ventricular function. The growth factor effects of insulin on the
      myocardium are worsened by hypertension. The diabetic hypertensive patient is
      exquisitely sensitive to blood pressure lowering as it relates to cardiac events
      and mortality. Because of this, the blood pressure goals for diabetic
      hypertensive patients are lower than those for their nondiabetic hypertensive
      peers. Cardiac events have a stronger association with systolic hypertension and
      the pulse pressure than with diastolic hypertension. The presence of
      microalbuminuria not only signifies a higher risk of developing diabetic
      nephropathy, but also increased mortality and incidence of cardiovascular events.
      Thus, when microalbuminuria is detected, intensification of hypertensive
      therapies, especially suppression of the renin-angiotensin-aldosterone system, is
      essential. CONCLUSION: The effects of hypertension in persons with diabetes
      increase the frequency and severity of cardiac events, especially when
      microalbuminuria is present.

PMID- 19095607
TI  - Metastatic renal cell carcinoma to the thyroid gland.
AB  - OBJECTIVE: To examine the presentation, diagnosis, and appropriate management of
      renal clear cell carcinoma metastasis to the thyroid gland. METHODS: We describe
      a clinical case of solitary thyroid metastasis from renal clear cell carcinoma
      and present a comprehensive review of the related English-language literature.
      Common patterns of presentation and generalized overall management
      recommendations are evaluated and summarized. RESULTS: Eight years after
      nephrectomy for renal carcinoma at age 61 years, a man presented with a thyroid
      mass. Cytology and histopathologic surgical findings were consistent with a
      solitary metastasis most compatible with metastatic clear cell carcinoma from his
      previous renal carcinoma. After left thyroid lobectomy and isthmusectomy, the
      patient remains disease-free 5 years later. Although uncommon, nearly 150 cases
      of clinically recognized metastatic renal cell carcinoma to the thyroid have been
      reported in the English-language literature. Metastatic disease from the kidney
      to the thyroid gland can occur more than 20 years after nephrectomy with the
      average time interval being 7.5 years. Obtaining a full clinical history in any
      patient who presents with a thyroid nodule is essential to allow consideration of
      possible metastatic disease from previous primary tumor. Metastatic disease to
      the thyroid gland can be correctly diagnosed preoperatively. If metastatic renal
      cancer is limited to the thyroid gland only, prompt, appropriate surgical
      intervention can be curative. CONCLUSION: Metastatic renal carcinoma to the
      thyroid should be considered in any patient presenting with a thyroid mass and a
      medical history of renal cell carcinoma.

PMID- 19095608
TI  - Intensive metabolic support: evolution and revolution.
AB  - OBJECTIVE: To describe a new aspect of critical care termed intensive metabolic
      support. METHODS: We performed a MEDLINE search of the English-language
      literature published between 1995 and 2008 for studies regarding the metabolic
      stages of critical illness, intensive insulin treatment, and intensive metabolic
      support in the intensive care unit, and we summarize the clinical data. RESULTS:
      Intensive metabolic support is a 3-component model involving metabolic control
      and intensive insulin therapy, early nutrition support, and nutritional
      pharmacology aimed at preventing allostatic overload and the development of
      chronic critical illness. To improve clinical outcome and prevent mortality,
      intensive metabolic support should start on arrival to the intensive care unit
      and should end only when patients are in the recovery phase of their illness.
      CONCLUSIONS: Intensive metabolic support should be an essential part of the daily
      treatment strategy in critical care medicine. This will involve a newfound and
      extensive collaboration between the endocrinologist and the intensivist. We call
      for well-designed future studies involving implementation of this protocol to
      decrease the burden of chronic critical illness.

PMID- 19095610
TI  - Visual vignette. Autoimmune hypophysitis (lymphocytic hypophysitis).

PMID- 19095609
TI  - The endocrinopathies of anorexia nervosa.
AB  - OBJECTIVE: To describe the hormonal adaptations and alterations in anorexia
      nervosa. METHODS: We performed a PubMed search of the English-language literature
      related to the pathophysiology of the endocrine disorders observed in anorexia
      nervosa, and we describe a case to illustrate these findings. RESULTS: Anorexia
      nervosa is a devastating disease with a variety of endocrine manifestations. The
      effects of starvation are extensive and negatively affect the pituitary gland,
      thyroid gland, adrenal glands, gonads, and bones. Appetite is modulated by the
      neuroendocrine system, and characteristic patterns of leptin and ghrelin
      concentrations have been observed in anorexia nervosa. A thorough understanding
      of refeeding syndrome is imperative to nutrition rehabilitation in these patients
      to avoid devastating consequences. Although most endocrinopathies associated with
      anorexia nervosa reverse with recovery, short stature, osteoporosis, and
      infertility may be long-lasting complications. We describe a 20-year-old woman
      who presented with end-stage anorexia nervosa whose clinical course reflects the
      numerous complications caused by this disease. CONCLUSIONS: The effects of severe
      malnutrition and subsequent refeeding are extensive in anorexia nervosa.
      Nutrition rehabilitation is the most appropriate treatment for these patients;
      however, it must be done cautiously.

PMID- 19095611
TI  - Visual vignette. Metastatic neuroendocrine tumor.

PMID- 19095612
TI  - EDTA-dependent lymphoagglutination.
AB  - Lymphoagglutination is an extremely rare EDTA-dependent phenomenon and is far
      less frequent than neutrophil agglutination. We describe 6 new cases and briefly
      review the literature on lymphoagglutination.

PMID- 19095614
TI  - Ex vivo coagulation test on tissue factor-expressing cells with a calibrated
      automated thrombogram.
AB  - A calibrated automated thrombogram is not affected by the turbidity of platelet
      and cell preparations because the measurement is based on fluorescence. To
      examine conditions that mimic the physiological state, we investigated
      thrombograms that show thrombin generation on tissue factor (TF)-bearing cells.
      An increase in the number of J82 cells did not affect the endogenous thrombin
      potential (ETP) of normal plasma, although the lag time (LT), the peak height,
      and the time to peak (ttPeak) did depend on cell concentration. When 5 parameters
      of coagulation factor-deficient plasmas were plotted on a radar graph, the
      thrombogram pattern of factor XI (FXI)-deficient plasma became slightly reduced.
      The thrombogram did not improve when washed normal platelets or washed normal
      platelets with adenosine diphosphate (ADP) were added. FVII-depleted plasma,
      FVIII-deficient plasma, and FIX-deficient plasma showed remarkably reduced peak
      heights, ttPeaks, and times to the end of thrombin generation (start tails). The
      thrombogram of FVII-depleted plasma was characterized by a remarkably prolonged
      LT, unlike the patterns of FVIII- or FIX-deficient plasma and FXI-depleted
      plasma. The ETP of FVIII- and FIX-deficient plasma, but not FVII-depleted plasma,
      improved significantly upon addition of washed normal platelets or washed normal
      platelets with ADP. The thrombograms of coagulation factor-deficient plasma
      containing TF-bearing cells differed from those for recombinant TF and
      phospholipid in the liquid phase. We suggest that thrombograms using TF-bearing
      cells can be a useful ex vivo test, because this experimental model may be
      analogous to most coagulation processes in vivo.

PMID- 19095615
TI  - Stochastic dynamics and non-equilibrium thermodynamics of a bistable chemical
      system: the Schlogl model revisited.
AB  - Schlogl's model is the canonical example of a chemical reaction system that
      exhibits bistability. Because the biological examples of bistability and
      switching behaviour are increasingly numerous, this paper presents an integrated
      deterministic, stochastic and thermodynamic analysis of the model. After a brief
      review of the deterministic and stochastic modelling frameworks, the concepts of
      chemical and mathematical detailed balances are discussed and non-equilibrium
      conditions are shown to be necessary for bistability. Thermodynamic quantities
      such as the flux, chemical potential and entropy production rate are defined and
      compared across the two models. In the bistable region, the stochastic model
      exhibits an exchange of the global stability between the two stable states under
      changes in the pump parameters and volume size. The stochastic entropy production
      rate shows a sharp transition that mirrors this exchange. A new hybrid model that
      includes continuous diffusion and discrete jumps is suggested to deal with the
      multiscale dynamics of the bistable system. Accurate approximations of the
      exponentially small eigenvalue associated with the time scale of this switching
      and the full time-dependent solution are calculated using Matlab. A breakdown of
      previously known asymptotic approximations on small volume scales is observed
      through comparison with these and Monte Carlo results. Finally, in the appendix
      section is an illustration of how the diffusion approximation of the chemical
      master equation can fail to represent correctly the mesoscopically interesting
      steady-state behaviour of the system.

PMID- 19095616
TI  - Dyskeratosis congenita mutations in the H/ACA domain of human telomerase RNA
      affect its assembly into a pre-RNP.
AB  - Dyskeratosis congenita (DC) is an inherited disorder that implicates defects in
      the biology of telomeres, which are maintained by telomerase, a ribonucleoprotein
      with reverse transcriptase activity. Like all H/ACA RNAs, the H/ACA domain of
      nascent human telomerase RNA (hTR) forms a pre-RNP with H/ACA proteins NAF1,
      dyskerin, NOP10, and NHP2 in vivo. To assess the pre-RNP assembly of hTR mutants
      that poorly accumulate in vivo, we developed an in vitro system that uses
      components of human origin. Pre-RNPs were reconstituted with synthetic (32)P
      labeled RNAs and (35)S-labeled proteins produced in rabbit reticulocyte lysate,
      and immunoprecipitations were carried out to analyze RNP formation. We show that
      human NAF1 cannot bind directly to the H/ACA domain of hTR, and requires the core
      trimer dyskerin-NOP10-NHP2 to be efficiently incorporated into the pre-RNP. This
      order of assembly seems common to H/ACA RNAs since it was observed with snoRNA
      ACA36 and scaRNA U92, which are predicted to guide pseudouridylation of 18S rRNA
      and U2 snRNA, respectively. However, the processing H/ACA snoRNA U17 did not
      conform to this rule, as NAF1 alone was able to bind it. We also provide the
      first evidence that DC-related mutations of hTR C408G and Delta378-451 severely
      impair pre-RNP assembly. Integrity of boxes H and ACA of hTR are also crucial for
      pre-RNP assembly, while the CAB box is dispensable. Our results offer new
      insights into the defects caused by some mutations located in the H/ACA domain of
      hTR.

PMID- 19095617
TI  - A role for the 30S subunit E site in maintenance of the translational reading
      frame.
AB  - The exit (E) site has been implicated in several ribosomal activities, including
      translocation, decoding, and maintenance of the translational reading frame.
      Here, we target the 30S subunit E site by introducing a deletion in rpsG that
      truncates the beta-hairpin of ribosomal protein S7. This mutation (S7DeltaR77
      Y84) increases both -1 and +1 frameshifting but does not increase miscoding,
      providing evidence that the 30S E site plays a specific role in frame
      maintenance. Mutation S7DeltaR77-Y84 also stimulates +1 programmed frameshifting
      during prfB'-lacZ translation in many synthetic contexts. However, no effect is
      seen when the E codon of the frameshift site corresponds to those found in
      nature, suggesting that E-tRNA release does not normally limit the rate of prfB
      frameshifting. Ribosomes containing S7DeltaR77-Y84 exhibit an elevated rate of
      spontaneous reverse translocation and an increased K (1/2) for E-tRNA. These
      effects are of similar magnitude, suggesting that both result from
      destabilization of E-tRNA. Finally, this mutation of the 30S E site does not
      inhibit EF-G-dependent translocation, consistent with a primary role for the 50S
      E site in the mechanism.

PMID- 19095618
TI  - Actin filament labels for localizing protein components in large complexes viewed
      by electron microscopy.
AB  - Localizing specific components in three-dimensional reconstructions of protein
      complexes visualized in an electron microscope increases the scientific value of
      those structures. Subunits are often identified within the complex by labeling;
      however, unless the label produces directly visible features, it must be detected
      by computational comparison with unlabeled complex. To bypass this step, we
      generated a cloneable tag from the actin-nucleating protein Spire that produces a
      directly visible "pointer" to the subunit after actin polymerization. We have
      used this new label to identify the intron of the C complex spliceosome to its
      small domain by fusing the 10 kDa Spire moiety to the affinity label that binds
      recombinant stem loops in the pre-mRNA substrate and assembling an actin filament
      on the particle.

PMID- 19095619
TI  - Mapping metal-binding sites in the catalytic domain of bacterial RNase P RNA.
AB  - Ribonuclease P (RNase P) is a ribonucleoprotein enzyme that contains a
      universally conserved, catalytically active RNA component. RNase P RNA requires
      divalent metal ions for folding, substrate binding, and catalysis. Despite recent
      advances in understanding the structure of RNase P RNA, no comprehensive analysis
      of metal-binding sites has been reported, in part due to the poor crystallization
      properties of this large RNA. We have developed an abbreviated yet still
      catalytic construct, Bst P7Delta RNA, which contains the catalytic domain of the
      bacterial RNase P RNA and has improved crystallization properties. We use this
      mutant RNA as well as the native RNA to map metal-binding sites in the catalytic
      core of the bacterial RNase P RNA, by anomalous scattering in diffraction
      analysis. The results provide insight into the interplay between RNA structure
      and focalization of metal ions, and a structural basis for some previous
      biochemical observations with RNase P. We use electrostatic calculations to
      extract the potential functional significance of these metal-binding sites with
      respect to binding Mg(2+). The results suggest that with at least one important
      exception of specific binding, these sites mainly map areas of diffuse
      association of magnesium ions.

PMID- 19095620
TI  - Pre-tRNA turnover catalyzed by the yeast nuclear RNase P holoenzyme is limited by
      product release.
AB  - Ribonuclease P (RNase P) is a ribonucleoprotein that catalyzes the 5' maturation
      of precursor transfer RNA in the presence of magnesium ions. The bacterial RNase
      P holoenzyme consists of one catalytically active RNA component and a single
      essential but catalytically inactive protein. In contrast, yeast nuclear RNase P
      is more complex with one RNA subunit and nine protein subunits. We have devised
      an affinity purification protocol to gently and rapidly purify intact yeast
      nuclear RNase P holoenzyme for transient kinetic studies. In pre-steady-state
      kinetic studies under saturating substrate concentrations, we observed an initial
      burst of tRNA formation followed by a slower, linear, steady-state turnover, with
      the burst amplitude equal to the concentration of the holoenzyme used in the
      reaction. These data indicate that the rate-limiting step in turnover occurs
      after pre-tRNA cleavage, such as mature tRNA release. Additionally, the steady
      state rate constants demonstrate a large dependence on temperature that results
      in nonlinear Arrhenius plots, suggesting that a kinetically important
      conformational change occurs during catalysis. Finally, deletion of the 3'
      trailer in pre-tRNA has little or no effect on the steady-state kinetic rate
      constants. These data suggest that, despite marked differences in subunit
      composition, the minimal kinetic mechanism for cleavage of pre-tRNA catalyzed by
      yeast nuclear RNase P holoenzyme is similar to that of the bacterial RNase P
      holoenzyme.

PMID- 19095621
TI  - A signal relay between ribosomal protein S12 and elongation factor EF-Tu during
      decoding of mRNA.
AB  - Codon recognition by aminoacyl-tRNA on the ribosome triggers a process leading to
      GTP hydrolysis by elongation factor Tu (EF-Tu) and release of aminoacyl-tRNA into
      the A site of the ribosome. The nature of this signal is largely unknown. Here,
      we present genetic evidence that a specific set of direct interactions between
      ribosomal protein S12 and aminoacyl-tRNA, together with contacts between S12 and
      16S rRNA, provide a pathway for the signaling of codon recognition to EF-Tu.
      Three novel amino acid substitutions, H76R, R37C, and K53E in Thermus
      thermophilus ribosomal protein S12, confer resistance to streptomycin. The
      streptomycin-resistance phenotypes of H76R, R37C, and K53E are all abolished by
      the mutation A375T in EF-Tu. A375T confers resistance to kirromycin, an
      antibiotic freezing EF-Tu in a GTPase activated state. H76 contacts aminoacyl
      tRNA in ternary complex with EF-Tu and GTP, while R37 and K53 are involved in the
      conformational transition of the 30S subunit occurring upon codon recognition. We
      propose that codon recognition and domain closure of the 30S subunit are signaled
      through aminoacyl-tRNA to EF-Tu via these S12 residues.

PMID- 19095622
TI  - Intensive glycemic control and the prevention of cardiovascular events:
      implications of the ACCORD, ADVANCE, and VA diabetes trials: a position statement
      of the American Diabetes Association and a scientific statement of the American
      College of Cardiology Foundation and the American Heart Association.

PMID- 19095623
TI  - Using antibody arrays to detect microparticles from acute coronary syndrome
      patients based on cluster of differentiation (CD) antigen expression.
AB  - Microparticles circulate in plasma and have recently emerged as potential
      inflammatory markers in cardiovascular disease. They are fragments of cell
      membranes that express cluster of differentiation (CD) antigens and are present
      at elevated levels in patients with acute coronary syndrome. We have developed a
      novel method for the rapid detection of microparticles in plasma using a
      fluorescence-based antibody array system. Isolated microparticles are captured on
      anti-CD antibody spots immobilized on a nitrocellulose membrane. These CD
      antibodies are directed against extracellular epitopes, whereas the intracellular
      exposed surface of the microparticles is labeled with a fluorescent anti-annexin
      antibody. The array is then scanned and quantified. A pilot study was undertaken
      to compare microparticle CD antigen expression in acute coronary syndrome and
      healthy subjects. Ten CD antigens (44, 45, 54, 62E, 79, 102, 117, 130, 138, and
      154) had significantly increased expression in the disease group relative to the
      healthy controls. These results were then verified using flow cytometry and
      scanning electron microscopy. Although we have focused our analysis on changes in
      microparticle CD antigen expression, this technique is amenable to analyzing
      other surface markers. Microparticles can be derived from a wide variety of cell
      types, so selection of the primary antibody can be tailored to the cell origin
      that is to be investigated.

PMID- 19095624
TI  - Activity-based electrical stimulation training in a stroke patient with minimal
      movement in the paretic upper extremity.
AB  - BACKGROUND: Existing task-specific practice interventions do not increase
      movement in stroke patients exhibiting minimal distal movement in the paretic
      upper extremity. Although often used, an important limitation of conventional
      electrical stimulation is that it does not involve task-specific practice.
      OBJECTIVE: To determine the impact of an activity-specific electrical stimulation
      program on paretic limb impairment, functional limitation, and ability to perform
      valued activities in a subacute stroke patient exhibiting minimal paretic wrist
      and hand movement. METHOD: A female subject exhibiting trace paretic hand and
      finger movement was administered, 9 months after stroke, the upper extremity
      section of the Fugl-Meyer Impairment Scale (FM), the Action Research Arm Test
      (ARAT), and the Arm Motor Ability Test (AMAT). She then engaged in paretic upper
      extremity, task-specific training incorporating an electrical stimulation
      neuroprosthesis. Training occurred 3 hours per day, 5 days per week for 3 weeks.
      The FM, ARAT, and AMAT were again administered. RESULTS: After intervention, she
      exhibited reduced impairment (evidenced by an FM score change of 22 to 29),
      decreased functional limitation (evidenced by an ARAT score change of 4 to 10),
      and increased ability and speed in performing valued AMAT activities. She also
      reported using the paretic hand and fingers more and new abilities to perform
      valued activities such as playing piano. CONCLUSION: Although conventional
      paretic upper extremity training strategies are ineffective in patients at this
      level, electrical stimulation training incorporating a neuroprosthesis appears
      promising.

PMID- 19095629
TI  - Chronic urticaria in children.

PMID- 19095630
TI  - Three-year outcome data of second-line antiretroviral therapy in Ugandan adults:
      good virological response but high rate of toxicity.
AB  - OBJECTIVE: To evaluate the safety and virological response to lopinavir/ritonavir
      containing second-line therapy after failing a first line nonnucleoside reverse
      transcriptase inhibitor (NNRTI) based regimen. DESIGN: Prospective 36 months
      cohort study of patients switched to zidovudine/stavudine plus didanosine plus
      lopinavir/ritonavir capsules as second-line regimen. METHODOLOGY: Structured
      interview, medical examination, and laboratory assessment performed every 6
      months. RESULTS: We enrolled 40 patients; 1 died and 3 were lost to follow-up.
      Median CD4+ count at baseline was 108 cell/microL, median log viral load was 4.8
      copies/mL. Sixteen (40%) patients had baseline genotypic resistant test, 14 (87%)
      had lamivudine resistance mutations, and all had NNRTIs resistance mutations. At
      month 36, 82% of the patients achieved viral suppression (<400 copies/ mL) and
      the median increase in CD4+ count was 214 cell/microL, (interquartile range: 128
      295). Twenty-five patients (62%) experienced at least one adverse event.
      CONCLUSIONS: Our study confirms lopinavir/ ritonavir-based second-line regimen
      but with a high rate of toxicities.

PMID- 19095631
TI  - Prostanoids in health and disease.
AB  - The prostanoids are a family of lipid mediators generated by the action of
      cyclooxygenase on a 20-carbon unsaturated fatty acid, arachidonic acid.
      Prostanoids are generated widely in response to diverse stimuli and, acting in a
      paracrine or autocrine manner, play important roles in normal physiology and
      disease. This review summarizes the current knowledge on prostanoid generation
      and the roles of individual mediators, their biosynthetic pathways, and their
      receptors in health and disease.

PMID- 19095635
TI  - Bilateral carotid bifurcation thrombi caused by neck overextension: case report
      and review of the literature.

PMID- 19095637
TI  - Commentary on "Setting up an outpatient imaging center: adding computed
      tomographic angiography, magnetic resonance angiography, and an outpatient
      angiography suite to surgeon-run vascular laboratories".

PMID- 19095638
TI  - Commentary. Anand, Yusuf, Xie, et al. The Warfarin Antiplatelet Vascular
      Evaluation Trial Investigators. Oral anticoagulation and antiplatelet therapy and
      peripheral arterial disease. N Engl J Med. 2007;357:217-227.

PMID- 19095639
TI  - Commentary. Prinssen, buskens, de jong, et Al. Cost-effectiveness of conventional
      and endovascular repair of abdominal aortic aneurysms: results of a clinical
      trial. J vasc surg. 2007;46:883-890.

PMID- 19095640
TI  - Commentary. Pawaskar M, Satiani B, Balkrishnan R, Starr JE. Economic evaluation
      of carotid artery stenting versus carotid endarterectomy for the treatment of
      carotid artery stenosis. J Am Coll Surg. 2007;205:413-419.

PMID- 19095641
TI  - Commentary. Lam RC, Shah S, Faries PL, McKinsey JF, Kent KC, Morrissey NJ.
      Incidence and clinical significance of distal embolization during percutaneous
      interventions involving the superficial femoral artery. J Vasc Surg. 2007;46:1155
      1159.

PMID- 19095642
TI  - Ceramide synthase inhibition by fumonisin B1 causes accumulation of 1
      deoxysphinganine: a novel category of bioactive 1-deoxysphingoid bases and 1
      deoxydihydroceramides biosynthesized by mammalian cell lines and animals.
AB  - Fumonisin B(1) (FB(1)) is a mycotoxin that inhibits ceramide synthases (CerS) and
      causes kidney and liver toxicity and other disease. Inhibition of CerS by FB(1)
      increases sphinganine (Sa), Sa 1-phosphate, and a previously unidentified
      metabolite. Analysis of the latter by quadrupole-time-of-flight mass spectrometry
      assigned an m/z = 286.3123 in positive ionization mode, consistent with the
      molecular formula for deoxysphinganine (C(18)H(40)NO). Comparison with a
      synthetic standard using liquid chromatography, electrospray tandem mass
      spectrometry identified the metabolite as 1-deoxysphinganine (1-deoxySa) based on
      LC mobility and production of a distinctive fragment ion (m/z 44, CH(3)CH=NH
      (+)(2)) upon collision-induced dissociation. This novel sphingoid base arises
      from condensation of alanine with palmitoyl-CoA via serine palmitoyltransferase
      (SPT), as indicated by incorporation of l-[U-(13)C]alanine into 1-deoxySa by Vero
      cells; inhibition of its production in LLC-PK(1) cells by myriocin, an SPT
      inhibitor; and the absence of incorporation of [U-(13)C]palmitate into 1
      [(13)C]deoxySa in LY-B cells, which lack SPT activity. LY-B-LCB1 cells, in which
      SPT has been restored by stable transfection, however, produce large amounts of 1
      [(13)C]deoxySa. 1-DeoxySa was elevated in FB(1)-treated cells and mouse liver and
      kidney, and its cytotoxicity was greater than or equal to that of Sa for LLC
      PK(1) and DU-145 cells. Therefore, this compound is likely to contribute to
      pathologies associated with fumonisins. In the absence of FB(1), substantial
      amounts of 1-deoxySa are made and acylated to N-acyl-1-deoxySa (i.e. 1
      deoxydihydroceramides). Thus, these compounds are an underappreciated category of
      bioactive sphingoid bases and "ceramides" that might play important roles in cell
      regulation.

PMID- 19095643
TI  - NF-kappaB transcription factor p50 critically regulates tissue factor in deep
      vein thrombosis.
AB  - NF-kappaB transcription factors regulate the expression of tissue factor (TF), a
      principal initiator of the coagulation cascade. Dominant among them is the
      p50/p65 heterodimer. Here we report that Andrographolide (Andro; a p50 inhibitor)
      and genetic deletion of p50 attenuated TF activity in stimulated endothelial
      cells and monocytes/macrophages. Results of the electrophoretic mobility
      "supershift" assay and chromatin immunoprecipitation demonstrated the direct
      interaction of the p50/p65 heterodimer with the NF-kappaB site of the human TF
      promoter. Andro-treated and p50 null mice both exhibited blunted TF expression
      and reduced venous thrombosis, which were recapitulated by an anti-murine TF
      antibody in vivo. Our findings thus indicate that regulation of TF by NF-kappaB
      transcription factor p50 is essential for the pathogenesis of deep vein
      thrombosis and suggest that specific inhibitors of p50, such as Andro, may be
      therapeutically valuable for preventing and perhaps treating venous thrombosis.

PMID- 19095645
TI  - Redox intermediates of the Mn-Fe Site in subunit R2 of Chlamydia trachomatis
      ribonucleotide reductase: an X-ray absorption and EPR study.
AB  - The R2 protein of class I ribonucleotide reductase (RNR) from Chlamydia
      trachomatis (Ct) can contain a Mn-Fe instead of the standard Fe-Fe cofactor. Ct
      R2 has a redox-inert phenylalanine replacing the radical-forming tyrosine of
      classic RNRs, which implies a different mechanism of O(2) activation. We studied
      the Mn-Fe site by x-ray absorption spectroscopy (XAS) and EPR. Reduced R2 in the
      R1R2 complex (R2(red)) showed an isotropic six-line EPR signal at g approximately
      2 of the Mn(II)Fe(II) state. In oxidized R2 (R2(ox)), the Mn(III)Fe(III) state
      exhibited EPR g values of 2.013, 2.009, and 2.015. By XAS, Mn-Fe distances and
      oxidation states of intermediates were determined and assigned as follows:
      approximately 4.15 A, Mn(II)Fe(II); approximately 3.25 A, Mn(III)Fe(II);
      approximately 2.90 A, Mn(III)Fe(III); and approximately 2.75 A, Mn(IV)Fe(III).
      Shortening of the Mn/Fe-ligand bond lengths indicated formation of additional
      metal bridges, i.e. microO(H) and/or peroxidic species, upon O(2) activation at
      the site. The structural parameters suggest overall configurations of the Mn-Fe
      site similar to those of homo-metallic sites in other R2 proteins. However, the
      approximately 2.90 A and approximately 2.75 A Mn-Fe distances, typical for di
      microO(H) metal bridging, are shorter than inter-metal distances in any R2
      crystal structure. In diffraction data collection, such bridges may be lost due
      to rapid x-ray photoreduction of high-valent metal ions, as demonstrated here for
      Fe(III) by XAS.

PMID- 19095644
TI  - Rab1 guanine nucleotide exchange factor SidM is a major phosphatidylinositol 4
      phosphate-binding effector protein of Legionella pneumophila.
AB  - The causative agent of Legionnaires disease, Legionella pneumophila, forms a
      replicative vacuole in phagocytes by means of the intracellular
      multiplication/defective organelle trafficking (Icm/Dot) type IV secretion system
      and translocated effector proteins, some of which subvert host GTP and
      phosphoinositide (PI) metabolism. The Icm/Dot substrate SidC anchors to the
      membrane of Legionella-containing vacuoles (LCVs) by specifically binding to
      phosphatidylinositol 4-phosphate (PtdIns(4)P). Using a nonbiased screen for novel
      L. pneumophila PI-binding proteins, we identified the Rab1 guanine nucleotide
      exchange factor (GEF) SidM/DrrA as the predominant PtdIns(4)P-binding protein.
      Purified SidM specifically and directly bound to PtdIns(4)P, whereas the SidM
      interacting Icm/Dot substrate LidA preferentially bound PtdIns(3)P but also
      PtdIns(4)P, and the L. pneumophila Arf1 GEF RalF did not bind to any PIs. The
      PtdIns(4)P-binding domain of SidM was mapped to the 12-kDa C-terminal sequence,
      termed "P4M" (PtdIns4P binding of SidM/DrrA). The isolated P4M domain is largely
      helical and displayed higher PtdIns(4)P binding activity in the context of the
      alpha-helical, monomeric full-length protein. SidM constructs containing P4M were
      translocated by Icm/Dot-proficient L. pneumophila and localized to the LCV
      membrane, indicating that SidM anchors to PtdIns(4)P on LCVs via its P4M domain.
      An L. pneumophila DeltasidM mutant strain displayed significantly higher amounts
      of SidC on LCVs, suggesting that SidM and SidC compete for limiting amounts of
      PtdIns(4)P on the vacuole. Finally, RNA interference revealed that PtdIns(4)P on
      LCVs is specifically formed by host PtdIns 4-kinase IIIbeta. Thus, L. pneumophila
      exploits PtdIns(4)P produced by PtdIns 4-kinase IIIbeta to anchor the effectors
      SidC and SidM to LCVs.

PMID- 19095646
TI  - Thromboxane A2-induced bi-directional regulation of cerebral arterial tone.
AB  - Myosin light chain phosphatase plays a critical role in modulating smooth muscle
      contraction in response to a variety of physiologic stimuli. A downstream target
      of the RhoA/Rho-kinase and nitric oxide (NO)/cGMP/cyclic GMP-dependent kinase
      (cGKI) pathways, myosin light chain phosphatase activity reflects the sum of both
      calcium sensitization and desensitization pathways through phosphorylation and
      dephosphorylation of the myosin phosphatase targeting subunit (MYPT1). As
      cerebral blood flow is highly spatio-temporally modulated under normal
      physiologic conditions, severe perturbations in normal cerebral blood flow, such
      as in cerebral vasospasm, can induce neurological deficits. In nonpermeabilized
      cerebral vessels stimulated with U-46619, a stable mimetic of endogenous
      thromboxane A2 implicated in the etiology of cerebral vasospasm, we observed
      significant increases in contractile force, RhoA activation, regulatory light
      chain phosphorylation, as well as phosphorylation of MYPT1 at Thr-696, Thr-853,
      and surprisingly Ser-695. Inhibition of nitric oxide signaling completely
      abrogated basal MYPT1 Ser-695 phosphorylation and significantly increased and
      potentiated U-46619-induced MYPT1 Thr-853 phosphorylation and contractile force,
      indicating that NO/cGMP/cGKI signaling maintains basal vascular tone through
      active inhibition of calcium sensitization. Surprisingly, a fall in Ser-695
      phosphorylation did not result in an increase in phosphorylation of the Thr-696
      site. Although activation of cGKI with exogenous cyclic nucleotides inhibited
      thromboxane A2-induced MYPT1 membrane association, RhoA activation, contractile
      force, and regulatory light chain phosphorylation, the anticipated decreases in
      MYPT1 phosphorylation at Thr-696/Thr-853 were not observed, indicating that the
      vasorelaxant effects of cGKI are not through dephosphorylation of MYPT1. Thus,
      thromboxane A2 signaling within the intact cerebral vasculature induces
      "buffered" vasoconstrictions, in which both the RhoA/Rho-kinase calcium
      sensitizing and the NO/cGMP/cGKI calcium-desensitizing pathways are activated.

PMID- 19095648
TI  - The fine structure of Neisseria meningitidis lipooligosaccharide from the M986
      strain and three of its variants.
AB  - Neisseria meningitidis is a cause of fatal sepsis and epidemic meningitis. A
      major virulence factor is cell wall lipooligosaccharide (LOS). The M986 strain
      has been used extensively in immunological and vaccine research. Yet, the LOS
      repertoire of this strain is not known. Here we have investigated the LOS
      structures of M986 and three of its variants OP1, OP2-, and OP2+. This strain and
      its variants present a series of related LOS families that are increasingly
      truncated in their listed order. The major structural differences are seen in the
      lacto-N-neotetraose alpha-chain. The gamma-chain Hep II contains two
      phosphoethanolamine (PEA) substitutions at C3 and C6/7. These substitutions were
      seen in all strains except OP2+ where the canonical core Hep II is missing. The
      PEA disubstitution was present in nearly stoichiometric amounts with only minor
      amounts of monosubstitution observed, and no glycomers devoid of PEA were seen.
      This was also the case in LOS with a complete lacto-N-neotetraosyl alpha-chain
      even though previous reports suggested that the presence of an extended alpha
      chain hinders C3 PEA substitution of Hep II. Approximately 50% of gamma-chain
      GlcNAc was present in its 3-OAc-substituted form. Because Hep II C3 PEA
      substitution and gamma-chain GlcNAc OAc addition have been reported to negatively
      interact, the co-existence of these two modifications in these strains is unique.
      The LOS structures of M986 and three of its variants have been determined, which
      better defines these strains as tools for immunological and vaccine research.

PMID- 19095647
TI  - Tiam1 and Rac1 are required for platelet-activating factor-induced endothelial
      junctional disassembly and increase in vascular permeability.
AB  - It is known that platelet-activating factor (PAF) induces severe endothelial
      barrier leakiness, but the signaling mechanisms remain unclear. Here, using a
      wide range of biochemical and morphological approaches applied in both mouse
      models and cultured endothelial cells, we addressed the mechanisms of PAF-induced
      disruption of interendothelial junctions (IEJs) and of increased endothelial
      permeability. The formation of interendothelial gaps filled with filopodia and
      lamellipodia is the cellular event responsible for the disruption of endothelial
      barrier. We observed that PAF ligation of its receptor induced the activation of
      the Rho GTPase Rac1. Following PAF exposure, both Rac1 and its guanine nucleotide
      exchange factor Tiam1 were found associated with a membrane fraction from which
      they co-immunoprecipitated with PAF receptor. In the same time frame with Tiam1
      Rac1 translocation, the junctional proteins ZO-1 and VE-cadherin were relocated
      from the IEJs, and formation of numerous interendothelial gaps was recorded.
      Notably, the response was independent of myosin light chain phosphorylation and
      thus distinct from other mediators, such as histamine and thrombin. The changes
      in actin status are driven by the PAF-induced localized actin polymerization as a
      consequence of Rac1 translocation and activation. Tiam1 was required for the
      activation of Rac1, actin polymerization, relocation of junctional associated
      proteins, and disruption of IEJs. Thus, PAF-induced IEJ disruption and increased
      endothelial permeability requires the activation of a Tiam1-Rac1 signaling
      module, suggesting a novel therapeutic target against increased vascular
      permeability associated with inflammatory diseases.

PMID- 19095650
TI  - Distinctions between hydrophobic helices in globular proteins and transmembrane
      segments as factors in protein sorting.
AB  - Transmembrane (TM) segments in proteins can be distinguished in amino acid
      sequences as continuous stretches of hydrophobic residues. However, examination
      of a data base of helical water-soluble (globular) proteins revealed that nearly
      one-third contained helices of sufficient length to span a bilayer (> or =19
      residues) that had mean hydrophobicity > or =actual TM segments. We now report
      that synthetic peptides corresponding to these globular protein sequences, which
      we termed "delta-helices," behave like native TM sequences and readily insert
      into membrane mimetic environments in helical conformations. As well, certain
      delta-helix sequences can integrate into the membrane bilayer when placed into a
      membrane-targeted chimeric protein. We establish that delta-helices can be
      distinguished computationally from bona fide TM segments by the decreased
      frequency of occurrence of Ile/Val residues and by their relatively decreased
      solvent accessibilities (versus other globular helices) within tertiary
      structure. The further observations that (i) delta-helices generally contain
      three or more charged residues and (ii) delta-helices display relatively even
      distribution of these charged residues along their lengths, rather than
      concentration near their N and C termini as observed for TM segments, may
      constitute key recognition factors in diverting delta-helices from the membrane
      in vivo. Although a discrete biological role for delta-helices remains to be
      pinpointed, our overall results suggest that such segments may be required for
      globular protein folding and identify additional factors that may be important in
      the correct selection of TM segments by the cellular machinery.

PMID- 19095649
TI  - Sonic hedgehog-responsive genes in the fetal prostate.
AB  - The Hedgehog (Hh) signaling pathway plays an important role in prostate
      development and appears to play an equally important role in promoting growth of
      advanced prostate cancer. During prostate development, epithelial cells in the
      urogenital sinus (UGS) express Sonic Hedgehog (Shh) and secrete Shh peptide. The
      secreted Hh peptide acts on adjacent mesenchymal cells to activate the Hh signal
      transduction pathway and elicit paracrine effects on epithelial proliferation and
      differentiation. To identify mesenchymal targets of Shh signaling, we performed
      microarray analysis on a Shh-responsive, immortalized urogential sinus
      mesenchymal cell line. We found 68 genes that were up-regulated by Shh and 21
      genes that were down-regulated. Eighteen of those were selected for further study
      with Ptc1 and Gli1 serving as reference controls. We found 10 of 18 were also Hh
      regulated in primary UGS mesenchymal cells and 13 of 18 in the cultured UGS.
      Seven of 18 exhibited Shh-regulated expression in both assays (Igfbp-6, Igfbp-3,
      Fbn2, Ntrk3, Agpt4, Dmp1, and Mmp13). Three of the 18 genes contained putative
      Gli binding motifs that bound Gli1 peptide in electrophoretic mobility shift
      assays. With the exception of Tiam1, target gene expression generally showed no
      differences in the concentration dependence of ligand-induced expression, but we
      observed strikingly different responses to direct pathway activation by
      transfection with activated Smo, Gli1, and Gli2.

PMID- 19095651
TI  - Structural analysis of MED-1 reveals unexpected diversity in the mechanism of DNA
      recognition by GATA-type zinc finger domains.
AB  - MED-1 is a member of a group of divergent GATA-type zinc finger proteins recently
      identified in several species of Caenorhabditis. The med genes are
      transcriptional regulators that are involved in the specification of the mesoderm
      and endoderm precursor cells in nematodes. Unlike other GATA-type zinc fingers
      that recognize the consensus sequence (A/C/T)GATA(A/G), the MED-1 zinc finger
      (MED1zf) binds the larger and atypical site GTATACT(T/C)(3). We have examined the
      basis for this unusual DNA specificity using a range of biochemical and
      biophysical approaches. Most strikingly, we show that although the core of the
      MED1zf structure is similar to that of GATA-1, the basic tail C-terminal to the
      zinc finger unexpectedly adopts an alpha-helical structure upon binding DNA. This
      additional helix appears to contact the major groove of the DNA, making contacts
      that explain the extended DNA consensus sequence observed for MED1zf. Our data
      expand the versatility of DNA recognition by GATA-type zinc fingers and perhaps
      shed new light on the DNA-binding properties of mammalian GATA factors.

PMID- 19095652
TI  - Regulation of C-type lectin antimicrobial activity by a flexible N-terminal
      prosegment.
AB  - Members of the RegIII family of intestinal C-type lectins are directly
      antibacterial proteins that play a vital role in maintaining host-bacterial
      homeostasis in the mammalian gut, yet little is known about the mechanisms that
      regulate their biological activity. Here we show that the antibacterial
      activities of mouse RegIIIgamma and its human ortholog, HIP/PAP, are tightly
      controlled by an inhibitory N-terminal prosegment that is removed by trypsin in
      vivo. NMR spectroscopy revealed a high degree of conformational flexibility in
      the HIP/PAP inhibitory prosegment, and mutation of either acidic prosegment
      residues or basic core protein residues disrupted prosegment inhibitory activity.
      NMR analyses of pro-HIP/PAP variants revealed distinctive colinear backbone amide
      chemical shift changes that correlated with antibacterial activity, suggesting
      that prosegment-HIP/PAP interactions are linked to a two-state conformational
      switch between biologically active and inactive protein states. These findings
      reveal a novel regulatory mechanism governing C-type lectin biological function
      and yield new insight into the control of intestinal innate immunity.

PMID- 19095653
TI  - Coordination of eukaryotic translation elongation factor 1A (eEF1A) function in
      actin organization and translation elongation by the guanine nucleotide exchange
      factor eEF1Balpha.
AB  - Eukaryotic translation elongation factor 1A (eEF1A) both shuttles aminoacyl-tRNA
      (aa-tRNA) to the ribosome and binds and bundles actin. A single domain of eEF1A
      is proposed to bind actin, aa-tRNA and the guanine nucleotide exchange factor
      eEF1Balpha. We show that eEF1Balpha has the ability to disrupt eEF1A-induced
      actin organization. Mutational analysis of eEF1Balpha F163, which binds in this
      domain, demonstrates effects on growth, eEF1A binding, nucleotide exchange
      activity, and cell morphology. These phenotypes can be partially restored by an
      intragenic W130A mutation. Furthermore, the combination of F163A with the lethal
      K205A mutation restores viability by drastically reducing eEF1Balpha affinity for
      eEF1A. This also results in a consistent increase in actin bundling and partially
      corrected morphology. The consequences of the overlapping functions in this eEF1A
      domain and its unique differences from the bacterial homologs provide a novel
      function for eEF1Balpha to balance the dual roles in actin bundling and protein
      synthesis.

PMID- 19095654
TI  - 17beta-Estradiol modulates apoptosis in pancreatic beta-cells by specific
      involvement of the sulfonylurea receptor (SUR) isoform SUR1.
AB  - Apoptosis of pancreatic beta-cells is an important factor in the pathophysiology
      of diabetes. Previously, we have shown that the "phytoestrogen" resveratrol can
      induce beta-cell apoptosis dependent on the expression of sulfonylurea receptor
      (SUR) 1, the regulatory subunit of pancreatic ATP-sensitive K(+) channels. Here,
      we investigate whether 17beta-estradiol also influences beta-cell apoptosis in a
      SUR1-dependent manner. Therefore, islets from wild type or SUR1 knock-out mice,
      clonal beta-cells, or HEK293 cells expressing different SUR forms were treated
      with 17beta-estradiol or estrone. Different apoptotic parameters were determined
      and estrogen binding to SUR was analyzed. In murine islets, 17beta-estradiol
      treatment resulted in significant apoptotic changes, which in their nature
      (either apoptotic or anti-apoptotic) were dependent on the age of the animal.
      These effects were not observed in SUR1 knock-out mice. Furthermore, 17beta
      estradiol, which specifically binds to SUR, induced enhanced apoptosis in SUR1
      expressing HEK293 cells and clonal beta-cells, whereas apoptosis in recombinant
      cells expressing SUR2A or SUR2B (cardiac or vascular SUR-isoforms) or sham
      transfected control cells was significantly lower. The apoptotic potency of
      17beta-estradiol was much higher than that of resveratrol or estrone. SUR1
      specific 17beta-estradiol-induced apoptosis was either abolished by the mutation
      M1289T in transmembrane helix 17 of SUR1 or clearly enhanced by two mutations in
      nucleotide binding fold 2 (R1379C, R1379L). In conclusion, 17beta-estradiol
      treatment modulates beta-cell apoptosis under specific involvement of SUR1 in an
      age-dependent manner. 17beta-Estradiol-induced apoptosis can be influenced by
      certain SUR1 mutations. These findings may contribute to the understanding of
      pathophysiological changes in beta-cell mass and could, for instance, provide
      interesting aspects concerning the etiology of gestational diabetes.

PMID- 19095656
TI  - Inhibition of TRPM8 by icilin distinct from desensitization induced by menthol
      and menthol derivatives.
AB  - TRPM8 is a cation channel activated by cold temperatures and the chemical stimuli
      menthol and icilin. Both compounds use different mechanisms of current
      activation; amino acid residues within the S2-S3 linker have been identified
      critical for current activation by icilin but not by menthol. Current decline in
      the course of menthol stimulation reflects Ca(2+)-dependent desensitization
      attributed to phosphatidylinositol 4,5-bisphosphate depletion. Carboxyamide
      derivatives chemically resembling menthol have been described as activators of
      TRPM8 analogous to icilin. Our aim was a detailed analysis of whether differences
      exist between all these substances with respect to their activation and
      inactivation of currents. We studied wild-type TRPM8 as well as an s3-TRPM8
      mutant with mutations in the S2-S3 linker region that could not be activated by
      icilin. Menthol and menthol derivatives behaved indistinguishable in evoking
      currents through both channels in a Ca(2+)-independent manner as well as inducing
      Ca(2+)-dependent desensitization. Icilin, in contrast, activated currents only in
      wild type TRPM8 and in the presence of Ca(2+). Moreover, it completely reversed
      currents induced by menthol, menthol derivatives, and cold temperatures in wild
      type TRPM8 and s3-TRPM8; this current inhibition was independent of Ca(2+).
      Finally, icilin suppressed current activation by the other agonists. None of the
      inhibiting effects of icilin occurred in the cation channel TRPA1 that is also
      stimulated by both menthol and icilin. Thus, icilin specifically inhibits TRPM8
      independently of its interaction site within the S2-S3 linker through a process
      distinct from desensitization.

PMID- 19095655
TI  - Mechanistic insight into control of CFTR by AMPK.
AB  - The cystic fibrosis transmembrane conductance regulator (CFTR) is a cAMP and
      protein kinase A (PKA)-regulated Cl(-) channel in the apical membrane of
      epithelial cells. The metabolically regulated and adenosine monophosphate
      stimulated kinase (AMPK) is colocalized with CFTR and attenuates its function.
      However, the sites for CFTR phosphorylation and the precise mechanism of
      inhibition of CFTR by AMPK remain obscure. We demonstrate that CFTR normally
      remains closed at baseline, but nevertheless, opens after inhibition of AMPK.
      AMPK phosphorylates CFTR in vitro at two essential serines (Ser(737) and
      Ser(768)) in the R domain, formerly identified as "inhibitory" PKA sites.
      Replacement of both serines by alanines (i) reduced phosphorylation of the R
      domain, with Ser(768) having dramatically greater impact, (ii) produced CFTR
      channels that were partially open in the absence of any stimulation, (iii)
      significantly augmented their activation by IBMX/forskolin, and (iv) eliminated
      CFTR inhibition post AMPK activation. Attenuation of CFTR by AMPK activation was
      detectable in the absence of cAMP-dependent stimulation but disappeared in
      maximally stimulated oocytes. Our data also suggest that AMP is produced by local
      phosphodiesterases in close proximity to CFTR. Thus we propose that CFTR channels
      are kept closed in nonstimulated epithelia with high baseline AMPK activity but
      CFTR may be basally active in tissues with lowered endogenous AMPK activity.

PMID- 19095657
TI  - Mitochondrial DNA damage in iron overload.
AB  - Chronic iron overload has slow and insidious effects on heart, liver, and other
      organs. Because iron-driven oxidation of most biologic materials (such as lipids
      and proteins) is readily repaired, this slow progression of organ damage implies
      some kind of biological "memory." We hypothesized that cumulative iron-catalyzed
      oxidant damage to mtDNA might occur in iron overload, perhaps explaining the
      often lethal cardiac dysfunction. Real time PCR was used to examine the
      "intactness" of mttDNA in cultured H9c2 rat cardiac myocytes. After 3-5 days
      exposure to high iron, these cells exhibited damage to mtDNA reflected by
      diminished amounts of near full-length 15.9-kb PCR product with no change in the
      amounts of a 16.1-kb product from a nuclear gene. With the loss of intact mtDNA,
      cellular respiration declined and mRNAs for three electron transport chain
      subunits and 16 S rRNA encoded by mtDNA decreased, whereas no decrements were
      found in four subunits encoded by nuclear DNA. To examine the importance of the
      interactions of iron with metabolically generated reactive oxygen species, we
      compared the toxic effects of iron in wild-type and rho(o) cells. In wild-type
      cells, elevated iron caused increased production of reactive oxygen species,
      cytostasis, and cell death, whereas the rho(o) cells were unaffected. We conclude
      that long-term damage to cells and organs in iron-overload disorders involves
      interactions between iron and mitochondrial reactive oxygen species resulting in
      cumulative damage to mtDNA, impaired synthesis of respiratory chain subunits, and
      respiratory dysfunction.

PMID- 19095659
TI  - Dominant mutants of ceruloplasmin impair the copper loading machinery in
      aceruloplasminemia.
AB  - The multicopper oxidase ceruloplasmin plays a key role in iron homeostasis, and
      its ferroxidase activity is required to stabilize cell surface ferroportin, the
      only known mammalian iron exporter. Missense mutations causing the rare autosomal
      neurodegenerative disease aceruloplasminemia were investigated by testing their
      ability to prevent ferroportin degradation in rat glioma C6 cells silenced for
      endogenous ceruloplasmin. Most of the mutants did not complement (i.e. did not
      stabilize ferroportin) because of the irreversible loss of copper binding
      ability. Mutant R701W, which was found in a heterozygous very young patient with
      severe neurological problems, was unable to complement per se but did so in the
      presence of copper-glutathione or when the yeast copper ATPase Ccc2p was co
      expressed, indicating that the protein was structurally able to bind copper but
      that metal loading involving the mammalian copper ATPase ATP7B was impaired.
      Notably, R701W exerted a dominant negative effect on wild type, and it induced
      the subcellular relocalization of ATP7B. Our results constitute the first
      evidence of "functional silencing" of ATP7B as a novel molecular defect in
      aceruloplasminemia. The possibility to reverse the deleterious effects of some
      aceruloplasminemia mutations may disclose new possible therapeutic strategies.

PMID- 19095658
TI  - A role for protein phosphorylation in cytochrome P450 3A4 ubiquitin-dependent
      proteasomal degradation.
AB  - Cytochromes P450 (P450s) incur phosphorylation. Although the precise role of this
      post-translational modification is unclear, marking P450s for degradation is
      plausible. Indeed, we have found that after structural inactivation, CYP3A4, the
      major human liver P450, and its rat orthologs are phosphorylated during their
      ubiquitin-dependent proteasomal degradation. Peptide mapping coupled with mass
      spectrometric analyses of CYP3A4 phosphorylated in vitro by protein kinase C
      (PKC) previously identified two target sites, Thr(264) and Ser(420). We now
      document that liver cytosolic kinases additionally target Ser(478) as a major
      site. To determine whether such phosphorylation is relevant to in vivo CYP3A4
      degradation, wild type and CYP3A4 with single, double, or triple Ala mutations of
      these residues were heterologously expressed in Saccharomyces cerevisiae
      pep4Delta strains. We found that relative to CYP3A4wt, its S478A mutant was
      significantly stabilized in these yeast, and this was greatly to markedly
      enhanced for its S478A/T264A, S478A/S420A, and S478A/T264A/S420A double and
      triple mutants. Similar relative S478A/T264A/S420A mutant stabilization was also
      observed in HEK293T cells. To determine whether phosphorylation enhances CYP3A4
      degradation by enhancing its ubiquitination, CYP3A4 ubiquitination was examined
      in an in vitro UBC7/gp78-reconstituted system with and without cAMP-dependent
      protein kinase A and PKC, two liver cytosolic kinases involved in CYP3A4
      phosphorylation. cAMP-dependent protein kinase A/PKC-mediated phosphorylation of
      CYP3A4wt but not its S478A/T264A/S420A mutant enhanced its ubiquitination in this
      system. Together, these findings indicate that phosphorylation of CYP3A4
      Ser(478), Thr(264), and Ser(420) residues by cytosolic kinases is important both
      for its ubiquitination and proteasomal degradation and suggest a direct link
      between P450 phosphorylation, ubiquitination, and degradation.

PMID- 19095660
TI  - Mechanism of allosteric inhibition of N-acetyl-L-glutamate synthase by L
      arginine.
AB  - N-Acetylglutamate synthase (NAGS) catalyzes the first committed step in l
      arginine biosynthesis in plants and micro-organisms and is subject to feedback
      inhibition by l-arginine. This study compares the crystal structures of NAGS from
      Neisseria gonorrhoeae (ngNAGS) in the inactive T-state with l-arginine bound and
      in the active R-state complexed with CoA and l-glutamate. Under all of the
      conditions examined, the enzyme consists of two stacked trimers. Each monomer has
      two domains: an amino acid kinase (AAK) domain with an AAK-like fold but lacking
      kinase activity and an N-acetyltransferase (NAT) domain homologous to other GCN5
      related transferases. Binding of l-arginine to the AAK domain induces a global
      conformational change that increases the diameter of the hexamer by approximately
      10 A and decreases its height by approximately 20A(.) AAK dimers move 5A outward
      along their 2-fold axes, and their tilt relative to the plane of the hexamer
      decreases by approximately 4 degrees . The NAT domains rotate approximately 109
      degrees relative to AAK domains enabling new interdomain interactions.
      Interactions between AAK and NAT domains on different subunits also change. Local
      motions of several loops at the l-arginine-binding site enable the protein to
      close around the bound ligand, whereas several loops at the NAT active site
      become disordered, markedly reducing enzymatic specific activity.

PMID- 19095662
TI  - Phenotypes of the ovarian follicular basal lamina predict developmental
      competence of oocytes.
AB  - BACKGROUND: The ovarian follicular basal lamina underlies the epithelial membrana
      granulosa and maintains the avascular intra-follicular compartment. Additional
      layers of basal lamina occur in a number of pathologies, including pili annulati
      and diabetes. We previously found additional layers of follicular basal lamina in
      a significant percentage of healthy bovine follicles. We wished to determine if
      this phenomenon existed in humans, and if it was related to oocyte function in
      the bovine. METHODS AND RESULTS: We examined follicles from human ovaries (n =
      18) by electron microscopy and found that many follicles had additional layers of
      basal lamina. Oocytes (n = 222) from bovine follicles with normal or unusual
      basal laminas were isolated and their ability to undergo in vitro maturation,
      fertilization and culture to blastocyst was compared. Healthy bovine follicles
      with a single layer of basal lamina had oocytes with significantly (P < 0.01)
      greater developmental competence than healthy follicles with additional layers of
      follicular basal lamina (65% versus 28%). CONCLUSIONS: These findings provide
      direct evidence that the phenotype of the follicular basal lamina is related to
      oocyte competence.

PMID- 19095661
TI  - Mediation of Endogenous beta-Endorphin in the Plasma Glucose-Lowering Action of
      Herbal Products Observed in Type 1-Like Diabetic Rats.
AB  - Recently, there have been advances in the development of new substances effective
      in managing diabetic disorders. Opioid receptors couple multiple systems to
      result in various biological effects, although opioids are best known for
      analgesia. In the present review, we used our recent data to describe the advance
      in plasma glucose-lowering action of herbal products, especially the mediation of
      beta-endorphin in glucose homeostasis of insulin-deficient diabetes. In type 1
      like streptozotocin-induced diabetic rats, we identified many products purified
      from herbs that show a dose-dependent plasma glucose-lowering action. Increase in
      beta-endorphin secretion from the adrenal gland may activate peripheral opioid MU
      receptors (MOR) to enhance the expression of muscle glucose transporters and/or
      to reduce hepatic gluconeogenesis at the gene level, thereby leading to improved
      glucose utilization in peripheral tissues for amelioration of severe
      hyperglycemia. It has also been observed that stimulation of alpha(1)
      adrenoceptors (alpha(1)-ARs) in the adrenal gland by some herbal products is
      responsible for the increase in beta-endorphin secretion via a phospholipase C
      protein kinase dependent pathway. However, an increase in beta-endorphin
      secretion from the adrenal gland by herbal products can function via another
      receptor. New insights into the mediation of endogenous beta-endorphin activation
      of peripheral MOR by herbal products for regulation of glucose homeostasis
      without the presence of insulin have been established. Therefore, an increase in
      beta-endorphin secretion and/or direct stimulation of peripheral MOR via an
      insulin-independent action might serve as the potential target for development of
      a therapeutic agent or promising adjuvant in intensive plasma glucose control.

PMID- 19095664
TI  - Endometrial fluid is a specific and non-invasive biological sample for protein
      biomarker identification in endometriosis.
AB  - BACKGROUND: The development of non-invasive diagnostic methods for endometriosis
      requires sensitive and disease specific biomarkers. Here, we describe the use of
      aspirated endometrial fluid from women with and without endometriosis as a novel
      biological sample for biomarker discovery. METHODS: Differential protein
      expression profiling of aspirates from women with early endometriosis (n = 14),
      advanced endometriosis (n = 32) and without evidence of the disease (n = 32) was
      assessed by two-dimensional gel electrophoresis (2-DE). A biomarker validation
      study was performed in an independent cohort (early endometriosis n = 6 and
      advanced endometriosis n = 14, controls n = 15). RESULTS: The analysis resulted
      in the identification of 31 proteins showing statistically significant
      differences in expression. The proteins identified are related to cell
      signalling, cell death and cell movement, processes that may be involved in the
      onset and/or progression of endometriosis. The differences in expression observed
      for 14-3-3 (signal transduction) and moesin (cytoskeletal structure) were
      confirmed in an independent group of endometriosis patients. CONCLUSIONS:
      Endometrial fluid represents a novel sample for proteomic analysis offering
      reliable, disease specific information on protein expression, facilitating the
      discovery of biomarkers for endometriosis. The results described here complement
      previous proteomic studies, providing new endometriosis-related proteins to be
      validated as diagnostic markers.

PMID- 19095663
TI  - An RCT of metformin versus orlistat for the management of obese anovulatory
      women.
AB  - BACKGROUND: Treatment of obesity-related anovulation poses a significant clinical
      challenge. Occasionally, the use of antiobesity medications such as orlistat or
      insulin sensitizing agents such as metformin is sometimes indicated in these
      patients. This study aimed to compare the effects of metformin and orlistat for
      improving ovulation in obese anovulatory women. METHODS: This was an open-label
      RCT. A total of 40 women were randomized to receive either metformin (n = 20) or
      orlistat (n = 20). BMI as well as the androgen profile and the ovulatory status
      were assessed at baseline and at four weekly intervals for 3 months. Different
      anthropometric and endocrine parameters were also assessed as possible predictors
      of ovulation. RESULTS: There was no significant difference between the two study
      arms regarding the ovulation rate for metformin and orlistat [40% (n = 8/20) and
      25% (n = 5/20), respectively, P = 0.31]. Both arms showed a significant drop in
      the BMI, testosterone and androstendione concentrations (P < 0.05), but there was
      no difference between the two arms. Patients who ovulated had significantly lower
      concentrations of baseline LH, androstendione, dehydroepiandrosterone and free
      androgen index (P < 0.05). Among these factors, a low baseline LH was found to be
      the only independent predictor of ovulation (area under curve, 0.85).
      CONCLUSIONS: Both metformin and orlistat show a similar effect on weight loss,
      ovulation rates and androgen concentrations. However, the effects on ovulation
      rates need to be confirmed in larger studies. The presence of a low baseline
      serum LH was found to be the most important predictor of ovulation. The study was
      registered at clinicaltrials.gov. NCT00292799.

PMID- 19095665
TI  - The efficacy of the embryo transfer catheter in IVF and ICSI is operator
      dependent: a randomized clinical trial.
AB  - BACKGROUND: Embryo transfer is a crucial step in the IVF process. Most randomized
      prospective studies comparing transfer catheters have demonstrated significantly
      higher pregnancy rates with soft versus firm catheters, but none have taken the
      operator effect into account. Our aim was to perform a prospective randomized
      clinical trial comparing two catheters and to study interactions between
      catheters and operators. METHODS: A prospective randomized trial comparing the
      Cook K-SOFT-5100 and Frydman classical catheters 4.5 was performed. Three
      experienced operators participated in the trial, using a fixed distance transfer
      protocol. Primary end-point was clinical pregnancy rate, secondary end-points
      were rates of difficult transfer and of catheter failure. Patients were
      randomized by a computer program prior to embryo transfer. RESULTS: A total of
      1446 embryo transfers were performed in 1155 women undergoing IVF or ICSI
      treatment. A total of 723 cycles were randomized to the Cook catheter and 723
      cycles to the Frydman catheter. Following intention-to-treat analysis, the
      adjusted odds ratio of clinical pregnancy between for the Cook versus the Frydman
      catheter was 1.11 [95% confidence interval (95% CI) 0.89-1.38]. Odds ratios of
      clinical pregnancy between the Cook and Frydman catheters for the three operators
      were respectively 1.19 (95% CI 0.84-1.69), 2.35 (95% CI 1.40-3.95) and 0.69 (95%
      CI 0.48-0.99). CONCLUSIONS: Variation in pregnancy rates between embryo transfer
      catheters depends on variation between operators. Results from randomized
      clinical trials comparing embryo transfer catheters should not be generalized,
      because inconsistent conclusions may be unavoidable on the account of different
      proportions of cycles with transfers by each type of operator. The study was
      registered at clinicaltrials.gov. NCT00766714.

PMID- 19095666
TI  - Increased access to emergency contraception: why it may fail.
AB  - BACKGROUND: To explore why increased access to emergency contraception (EC)
      failed to reduce pregnancies in a recent randomized controlled trial. METHODS: We
      used multivariable logistic regression to identify risk factors for unintended
      pregnancy using data from a trial involving sexually active women (n = 1490, aged
      14-24 years) randomly assigned to either increased access or standard access to
      EC. We used predictive modeling to generate estimated pregnancy risk scores for
      each participant. We then examined EC use among women at low or high baseline
      risk of pregnancy. RESULTS: Gravidity, recent history of unprotected sex (within
      14 days of enrollment to study) and lower aversion to pregnancy predicted
      unintended pregnancy. Women in the increased access group were more likely than
      women in the standard access group to use EC repeatedly. This difference was
      significantly stronger (P = 0.03) among low risk women than high risk women
      [Relative risk (RR) 10.0, 95% confidence interval (CI) 6.5-15.4 and RR 5.5, 95%
      CI 3.8-7.9, respectively]. CONCLUSIONS: Increased access to EC had a greater
      impact on women who were at lower baseline risk of pregnancy. This may explain in
      part why increased access to EC has had no measurable benefit in clinical trials.

PMID- 19095667
TI  - Assisted conception following radical trachelectomy.
AB  - BACKGROUND: Radical trachelectomy (RT) has been established as a valuable
      fertility-preserving treatment in women with early stage cervical cancer. A
      number of these women will require assisted conception which may bring certain
      challenges to those managing treatment. An awareness of those challenges is
      essential to maximize outcome in terms of live birth rates. METHODS: All women
      who had undergone assisted conception following RT were assessed with respect to
      treatment management and pregnancy outcome. RESULTS: Pregnancy rates were good,
      with nine pregnancies in seven women treated. Difficulties in treatment were
      essentially related to isthmic stenosis. There was a clear need for trial embryo
      transfer (ET) prior to treatment and dilatation of the isthmus where necessary.
      The premature delivery rate was high (75% at <37 weeks), highlighting the
      importance of single ET to avoid multiple pregnancy. CONCLUSIONS: Assisted
      conception following RT is associated with a good pregnancy rate, although there
      is a high miscarriage and premature delivery rate. Treatment outcome should be
      maximized by careful patient preparation in terms of assessing the need for
      isthmic dilatation, and ET should be performed by an experienced operator.

PMID- 19095668
TI  - Effect of ghrelin on gonadotrophin secretion in women during the menstrual cycle.
AB  - BACKGROUND: It has been suggested that ghrelin may affect reproduction in animals
      by decreasing pituitary LH secretion. The role of ghrelin on LH secretion in
      women has not been investigated. Our aim was to assess the effect of ghrelin
      administration on basal and GnRH-induced LH secretion during the menstrual cycle.
      METHODS: Normally cycling women (n = 10) received on Day 3 of three consecutive
      cycles a single bolus i.v. of either ghrelin (1 microg/kg, cycle 1) or GnRH (100
      microg, cycle 2) or GnRH plus ghrelin (cycle 3). In cycle 1, ghrelin was also
      injected in late follicular and mid-luteal phase of the cycle. Saline was
      injected in a preceding cycle (cycle 1, control). Blood samples were taken before
      drugs or saline injection (time 0) as well as at -15, 15, 30, 45, 60, 75, 90 and
      120 min. RESULTS: Plasma ghrelin levels increased rapidly, peaking at 15 or 30
      min (P < 0.001), then decreased steadily, approaching pre-injection levels at 120
      min. Serum FSH, LH, estradiol and progesterone levels remained unchanged. The
      stimulating effect of GnRH on LH and FSH secretion was unaffected by ghrelin
      injection. In contrast to saline, ghrelin stimulated a significant increase in
      growth hormone levels. CONCLUSIONS: Under these experimental conditions, our
      results demonstrate for the first time the inability of a bolus of ghrelin to
      affect basal and GnRH-induced LH and FSH secretion. It is suggested that ghrelin
      does not play a major physiological role in gonadotrophin secretion in women.

PMID- 19095669
TI  - Preoperative work-up for patients with deeply infiltrating endometriosis:
      transvaginal ultrasonography must definitely be the first-line imaging
      examination.
AB  - BACKGROUND: Transvaginal ultrasonography (TVUS) has important advantages compared
      with transrectal ultrasonography (TRUS): it is less invasive, is cost-effective,
      is a familiar and well-accepted approach, and anesthesia is not required. We
      compared the accuracy of TVUS and TRUS for diagnosing rectal wall involvement in
      patients presenting with histologically proved deeply infiltrating endometriosis
      (DIE). METHODS: Prospective study of 134 patients with histologically proved DIE
      underwent preoperative investigations using both TVUS and TRUS. The radiologist
      (TVUS) and sonographer (TRUS) were unaware of the clinical findings but knew that
      DIE was suspected. RESULTS: DIE was confirmed histologically for all the
      patients. A rectal wall involvement was histologically proved for 75 patients
      (56%). For the diagnosis of infiltration of the intestinal wall, TVUS and TRUS,
      respectively, had a sensitivity of 90.7% and 96.0%, a specificity of 96.5% and
      100.0%, a positive predictive value of 97.1% and 100.0% and a negative predictive
      value of 88.9% and 95.2%. CONCLUSIONS: TVUS and TRUS have similar degrees of
      accuracy for predicting intestinal involvement. TVUS must be the first-line
      imaging process to perform for patients presenting with clinically suspected DIE.
      The question for the coming years is to define if it is necessary for TRUS to be
      carried out systematically in cases of clinically suspected DIE.

PMID- 19095670
TI  - Development of an animal experimental model to study the effects of
      levonorgestrel on the human endometrium.
AB  - BACKGROUND: This study was designed to develop an animal model to test the
      response of endometrium to local progestin delivery. METHODS: Proliferative human
      endometrium was subcutaneously grafted in two groups of SCID mice that received,
      2 days before, a subcutaneous estradiol (E(2)) pellet and, for half of them, an
      additional implant of levonorgestrel (LNG). Mice were sacrificed 1, 2, 3 or 4
      weeks after endometrial implantation and grafts were histologically analysed.
      Proliferation, steroid hormone receptors, blood vessels and stromal
      decidualization in both groups (E(2) and LNG) were immunohistologically evaluated
      and compared with proliferative endometrium and endometrium from women with an
      LNG intrauterine device. RESULTS: Grafts presented normal morphological
      endometrial characteristics. The expression of progesterone receptors was
      significantly decreased in glands and stroma of the LNG group as compared with
      the E(2) group at all times. A significant decrease was also observed in the
      stromal expression of estrogen receptor-alpha in the LNG group. At 4 weeks, the
      mean cross-sectional area of vessels was significantly higher after LNG
      treatment. CONCLUSIONS: These morphological and immunohistochemical
      characteristics are similar to those observed in women treated with local LNG.
      This mouse model might facilitate further investigations needed to understand the
      mechanisms responsible for the breakthrough bleeding frequently observed in
      progestin users.

PMID- 19095671
TI  - Evaluation of Ki-67 antigen expression in the zona reticularis of the adrenal
      cortex of female rats in persistent estrus.
AB  - BACKGROUND: Hyperandrogenism and chronic anovulation are basic characteristics of
      polycystic ovary syndrome (PCOS), and androgens from the adrenal glands play an
      important role in the hyperandrogenism. Our aim was to evaluate the proliferative
      activity in the zona reticularis cells of the adrenal cortex of female rats in
      persistent estrus, a model developed to mimic PCOS. METHODS: Forty-four female
      Wistar-Hannover rats were randomly divided into two groups: control (n = 17) and
      animals which received 1.25 mg testosterone propionate s.c. on the second day of
      life (n = 27). At 90 days of age, after confirmation of persistent estrus, the
      animals were sacrificed, and the adrenal glands were removed and fixed in 10%
      buffered formalin to investigate Ki-67 antigen (marker of proliferation)
      expression by immunohistochemical analysis. Student's t-test and Levene's test
      were used in the statistical analysis. RESULTS: The mean percentage of Ki-67
      stained nuclei per 1000 cells in the zona reticularis of the adrenal cortex was
      15.58 +/- 1.14 (SEM) and 51.59 +/- 1.81 in the control and persistent estrus
      animals, respectively (P < 0.001). CONCLUSIONS: Proliferative activity in the
      zona reticularis cells of the adrenal cortex of the androgenized female rats was
      significantly greater than that of the control animals.

PMID- 19095672
TI  - Gene copy number variations in Asian patients with congenital bilateral absence
      of the vas deferens.
AB  - BACKGROUND: Congenital bilateral absence of the vas deferens (CBAVD) is a
      distinct clinical entity accounting for approximately 25% of obstructive
      azoospermia in infertile men. The association between CBAVD and mutated CFTR
      (cystic fibrosis transmembrane conductance regulator) alleles is well
      demonstrated in Caucasians, but the identity of CBAVD-susceptibility genes
      remains elusive in Asians. We investigate genomic copy number variations (CNVs)
      in a patient cohort of Taiwan. METHODS AND RESULTS: Genome-wide screening for
      genetic CNVs was conducted on eight individuals with CBAVD using array-based
      comparative genomic hybridization. One recurrent CNV was detected on 3q26.1 in
      five patients, and another was detected on a reproduction-related gene PANK2 in
      two patients. For the former, we further characterized the breakpoints in CBAVD
      and assessed the incidence in healthy individuals by tiling path arrays. The
      deletion in each patient was confirmed, and seven out of the eight controls were
      also affected. Examination of the homozygous loss of PANK2 by PCR in a larger
      cohort showed a homozygous deletion in only one of the 26 CBAVD males, and not in
      any of the 20 azoospermic patients without CBAVD, nor in any of the 16 control
      subjects. CONCLUSIONS: Our results suggest that 3q26.1 may not be a critical
      region for CBAVD. Additionally no strong association was found for PANK2 in this
      reproduction disorder. Other reproduction-related genes, such as PBX1, BRD3,
      COL18A1 and HMOX1, identified by this initial study may inspire further
      investigation.

PMID- 19095673
TI  - Information processing, attention and visual-motor function of adolescents born
      after in vitro fertilization compared with spontaneous conception.
AB  - BACKGROUND: Adverse conditions during prenatal life are associated with changes
      in physical and mental functioning in later life, as shown in children born
      preterm or small for gestational age. While recently in IVF children
      cardiometabolic differences have been demonstrated, there might also be risks for
      disturbance in cognitive functions. Therefore, this study examined information
      processing, attention and visual-motor function in pubertal IVF children compared
      with spontaneously conceived controls from subfertile parents. Results of these
      cognitive functions were then related to cardiometabolic measures to explore
      whether both can be explained by changes in fetal programming due to IVF.
      METHODS: A total of 139 IVF and 143 control adolescents underwent various
      neuropsychological tests to measure information processing, attention and visual
      motor function. The results were then related to data on blood pressure and
      glucose levels previously obtained from the same groups. RESULTS: No differences
      between IVF and control adolescents were found in the various test results for
      information processing and attention. A slight difference was found between the
      groups for motor speed, but these scores were within the normal range for the
      test. No direct relation was found between cognitive measures and cardiometabolic
      outcome. CONCLUSIONS: Comparison of IVF adolescents and controls revealed no
      disturbances in information processing, attention and visual-motor function. In
      addition, these cognitive functions were not directly related to cardiometabolic
      outcome. Therefore, these results do not support the hypothesis that cognition is
      influenced by IVF conception or an altered programming of metabolic systems due
      to IVF, and indicate that cognitive abilities in IVF children, as measured by the
      tasks assessed, appear to develop normally.

PMID- 19095674
TI  - Expression of secretory leukocyte protease inhibitor and elafin in human
      fallopian tube and in an in-vitro model of Chlamydia trachomatis infection.
AB  - BACKGROUND: Secretory leukocyte protease inhibitor (SLPI) and elafin are anti
      protease and anti-microbial molecules with a role in innate immune defence. They
      have been demonstrated at multiple mucosal surfaces including those of the female
      reproductive tract. METHODS AND RESULTS: This study details their expression in
      human Fallopian tubes (ampullary region) throughout the menstrual cycle (n = 18)
      and from women with ectopic pregnancy (n = 6), and examined their regulation by
      infection with Chlamydia trachomatis in an in-vitro model. Quantitative real-time
      PCR analysis showed that SLPI and elafin were constitutively expressed in the
      Fallopian tube during the menstrual cycle but were increased in ectopic pregnancy
      (P < 0.05 versus early-mid luteal phase, P < 0.01 versus all phases,
      respectively). SLPI and elafin were immunolocalised to the Fallopian tube
      epithelium in biopsies from non-pregnant women and those with ectopic pregnancy.
      An in-vitro culture model of C. trachomatis infection of the OE-E6/E7 oviductal
      epithelial cell line showed that elafin mRNA expression was upregulated in
      response to chlamydial infection. CONCLUSION: These data suggest that SLPI and
      elafin have a role in the innate immune defence of the Fallopian tube in
      infection and ectopic pregnancy. Their role is likely to include regulation of
      protease activity, wound healing and tissue remodelling.

PMID- 19095675
TI  - Indicators for metabolic disturbances in anovulatory women with polycystic ovary
      syndrome diagnosed according to the Rotterdam consensus criteria.
AB  - BACKGROUND: Polycystic ovary syndrome (PCOS) is associated with metabolic
      abnormalities. It is debated whether all women with PCOS should be screened for
      metabolic abnormalities as these may vary with PCOS phenotype, age and ethnicity.
      The aims of this study were to assess the prevalence of metabolic abnormalities
      in Dutch anovulatory PCOS women and to define criteria for metabolic screening.
      METHODS: Anovulatory patients, diagnosed with PCOS according to the Rotterdam
      consensus criteria, underwent metabolic screening. Through stepwise multivariate
      analysis patient characteristics associated with metabolic syndrome (MetS) and
      insulin resistance (IR) were evaluated for their use as selection parameters for
      metabolic screening. RESULTS: Overall, prevalence of MetS and IR was 15.9% (n =
      25) and 14% (n = 22), respectively, in 157 PCOS women (age 29.0 +/- 4.8 years,
      BMI 26.1 +/- 6.7 kg/m(2)). Anovulatory hyperandrogenic women (with or without
      polycystic ovaries) had more often MetS and IR (with, 20.8 and 19.8%; without,
      100 and 40%, respectively) than non-hyperandrogenic PCOS women (0 and 1.8%; P <
      0.001). Waist circumference >83.5 cm along with increased free androgen index
      (FAI) had the most powerful association with the presence of MetS and IR (area
      under the receiver operating characteristic curve 0.912) and offered a reduction
      in the necessity of screening for metabolic derailments of about 50%.
      CONCLUSIONS: The hyperandrogenic PCOS phenotypes are highly linked to the
      presence of MetS and IR in Dutch PCOS women. Waist circumference combined with
      FAI was identified as an efficient combination test to select those PCOS women
      who should be screened for the presence of MetS and/or IR.

PMID- 19095676
TI  - Antioxidant treatment for heart failure: friend or foe?
AB  - Increasing studies demonstrate a pivotal role for oxidant stress in the
      pathophysiology of heart failure (HF). Recent meta-analyses also reveal the
      potential pitfall of a mono-dimensional antioxidant approach. This review article
      summarizes the main biological pathways involved in oxidant stress and HF, the
      possible deleterious nature of certain antioxidant monotherapy and proposes
      potential antioxidant strategies necessary to challenge specific HF aetiology and
      progression.

PMID- 19095678
TI  - Angst-driven medicine?
AB  - Side-by-side with the quintessential scientific process and humanistic values,
      doctors' behavior and decisions in the clinical encounter are increasingly
      influenced by 'foreign' considerations that are little mentioned and seldom
      recognized as a significant force. Many such issues can be identified in the
      literature. They include reactions to uncertainty and to fear of litigation or
      complaint; responses to pressures of managed care organizations; time
      constraints; avoidance of exposure to emotions and suffering; yielding to demands
      of patients or families; compromises made due to the presence of the computer as
      a third party in the encounter; and the accumulating effects of work-related
      stress. All these varied factors, many of them new in the arena or increasing in
      importance in recent years, often cause angst in the clinician. Thus, they may
      skew the doctor's behavior and decisions away from 'best' evidence-based and
      compassionate medical practice towards less optimal, but angst-reducing
      solutions. Several multifaceted approaches may prove useful in minimizing angst
      driven medicine and its potential harm, thus improving the quality of care.

PMID- 19095679
TI  - Temocillin revived.
AB  - Resistance in Gram-negative pathogens is an increasing concern, with carbapenems
      often appearing as the only acceptable treatment option in serious infections.
      Reviving older compounds that have fallen into disuse may help to alleviate this
      burden. Temocillin (6-alpha-methoxy-ticarcillin) is resistant to most if not all
      classical and extended-spectrum beta-lactamases and to AmpC enzymes. It is also
      chemically stable, allowing administration by continuous infusion.
      Pharmacokinetic/pharmacodynamic analysis, aided by Monte-Carlo simulations,
      suggests a breakpoint of 8 mg/L for the registered maximum dosage of 4 g daily.
      Temocillin's weaknesses, explaining its limited previous use, are a lack of
      activity against Gram-positive organisms, anaerobes and Pseudomonas. In settings
      where these are unlikely or are covered by other agents, temocillin may be
      useful, potentially 'sparing' carbapenems and having little apparent potential to
      select for Clostridium difficile.

PMID- 19095680
TI  - Sustainability for behaviour change in the fight against antibiotic resistance: a
      social marketing framework.
AB  - Antibiotic resistance is one of today's most urgent public health problems,
      threatening to undermine the effectiveness of infectious disease treatment in
      every country of the world. Specific individual behaviours such as not taking the
      entire antibiotic regimen and skipping doses contribute to resistance development
      as does the taking of antibiotics for colds and other illnesses that antibiotics
      cannot treat. Antibiotic resistance is as much a societal problem as it is an
      individual one; if mass behaviour change across the population does not occur,
      the problem of resistance cannot be mitigated at community levels. The problem is
      one that potentially can be solved if both providers and patients become
      sufficiently aware of the issue and if they engage in appropriate behaviours.
      Although a number of initiatives have been implemented in various parts of the
      world to elicit behaviour change, results have been mixed, and there is little
      evidence that trial programmes with positive outcomes serve as models of
      sustainability. In recent years, several scholars have suggested social marketing
      as the framework for behaviour change that has the greatest chance of sustained
      success, but the antibiotic resistance literature provides no specifics for how
      the principles of social marketing should be applied. This paper provides an
      overview of previous communication-based initiatives and offers a detailed
      approach to social marketing to guide future efforts.

PMID- 19095681
TI  - Emergence and persistence of integron structures harbouring VIM genes in the
      Children's Memorial Health Institute, Warsaw, Poland, 1998-2006.
AB  - OBJECTIVES: The aim was to perform a genetically detailed study of the emergence
      of metallo-beta-lactamase (MBL) genes in Pseudomonas spp. in the Children's
      Memorial Health Institute over a 9 year period. METHODS: Carbapenem-resistant
      Pseudomonas spp. isolates were collected from 1998 to 2006 and screened for MBL
      production. MBL-positive isolates were further investigated by a combination of
      genetic techniques including PCR, genomic location experiments using pulsed-field
      gel electrophoresis (PFGE) of I-Ceu1, S1 and SpeI digests, and sequencing.
      RESULTS: Of the 20 MBL-containing Pseudomonas isolates collected from 1998 to
      2006, 16 Pseudomonas aeruginosa isolates contained an identical class 1 integron
      structure. Two P. aeruginosa isolates contained the bla(VIM-2) gene, and two
      Pseudomonas putida isolates harboured the bla(VIM-4) gene cassette in different
      integron structures. PFGE analysis indicated that all bla(VIM-4)-containing P.
      aeruginosa isolates were closely related, whereas the P. putida isolates were
      not. All MBL genes in this study were chromosomally encoded, and all isolates
      harboured only one class 1 integron. The bla(VIM-2) isolates were clonal, and the
      genetic structure supporting the bla(VIM-2) gene was found in an identical
      chromosomal position. CONCLUSIONS: MBL gene emergence in this hospital has
      paralleled a 6-fold increase in carbapenem usage. We have found an increase in
      MBL gene diversity, MBL host organisms and MBL genetic support structures in the
      hospital over the 9 year study period. There is also compelling evidence of the
      persistence of individual strains in the hospital throughout the study period.
      This suggests that once MBL genes have emerged in a hospital environment, they
      are difficult to remove.

PMID- 19095682
TI  - Application of denaturing HPLC to rapidly identify rifampicin-resistant
      Mycobacterium tuberculosis in low- and high-prevalence areas.
AB  - OBJECTIVES: Since the emergence of multidrug-resistant and extensively drug
      resistant tuberculosis, there has been a call for a rapid assay to detect
      rifampicin-resistant strains that can be implemented into a routine service to
      analyse all strains in a specific geographical location. Denaturing HPLC (dHPLC)
      is a rapid screening test that can detect mutations in PCR amplicons. The aim of
      this study was to evaluate the dHPLC analysis of rifampicin-resistant
      Mycobacterium tuberculosis isolates using an extensive strain collection from
      Hong Kong and the UK and a collection of 84 consecutive clinical isolates.
      METHODS: DNA from 51 rifampicin-resistant M. tuberculosis strains from the UK and
      Hong Kong identified from 1996 to 2005 was extracted and each mutation was
      defined by capillary electrophoresis. A 400 bp PCR product was amplified from
      each strain, heteroduplexed with a known susceptible control (H37Rv) and analysed
      by dHPLC at 67.0 degrees C. RESULTS: Forty-five out of 51 (88.2%) rifampicin
      resistant strains with known DNA mutations were detected by dHPLC. Two out of 84
      clinical isolates were phenotypically rifampicin-resistant and dHPLC detected a
      mutation in the rpoB amplicon for both these isolates. dHPLC detected a mutation
      in 1 out of 82 phenotypically rifampicin-susceptible isolates (M482T, a non
      cluster I/II mutation). In a combined analysis of all strains and isolates,
      mutation detection by dHPLC analysis exhibited 88.2% sensitivity and 98.8%
      specificity. CONCLUSIONS: This study shows that dHPLC analysis is sensitive and
      specific and could be implemented in a routine clinical service.

PMID- 19095683
TI  - Glomerular filtration rates in HIV-infected patients treated with and without
      tenofovir: a prospective, observational study.
AB  - OBJECTIVES: The aim of our study was to assess the impact of plasma HIV-1 RNA
      level [viral load (VL)] variation and tenofovir exposure on kidney functions by
      analysing changes in calculated glomerular filtration rates (GFRs) over a 48 week
      period in patients with mild renal impairment. PATIENTS AND METHODS: A
      prospective observational study that included data from all consecutive HIV
      infected patients who attended a metabolic clinic was conducted. Included were
      adult, antiretroviral (ARV)-experienced, tenofovir-naive patients, whose kidney
      functions were evaluated by calculated GFR using the simplified Modification of
      Diet in Renal Disease study equation (MDRD). Tenofovir-exposed patients were
      patients who initiated tenofovir therapy at baseline and tenofovir-unexposed
      patients were patients whose ARV therapy did not include tenofovir. Participants
      were stratified into three sub-groups according to the plasma HIV-1 RNA (VL)
      changes observed: sub-groups 1, 2 and 3 were patients with stable VL < or =50
      copies/mL, >0.5 log(10) VL increases and >0.5 VL log(10) decreases, respectively.
      RESULTS: Ninety-nine patients were enrolled and included in the analysis. Within
      the tenofovir-unexposed group, GFRs remained stable (ANOVA, P = 0.94) over the
      follow-up period. Within the tenofovir-exposed group, mean GFR changes varied
      significantly by sub-group (ANOVA, P < 0.01). In particular, GFR changes in sub
      group 3 (+8.4 +/- 12.4 mL/min) were different from those seen in sub-group 1 (
      1.0 +/- 8.8 mL/min) (P < 0.05) and sub-group 2 (-4.6 +/- 8.8 mL/min) (P < 0.01).
      CONCLUSIONS: Observed improvements in GFR that occurred as a consequence of
      highly active ARV therapy-induced viral suppression may have more than offset any
      potential negative effects of tenofovir on renal function.

PMID- 19095684
TI  - Tamoxifen as a potential antileishmanial agent: efficacy in the treatment of
      Leishmania braziliensis and Leishmania chagasi infections.
AB  - OBJECTIVES: The aim of this study was to evaluate the efficacy of tamoxifen in
      vivo in experimental models of cutaneous (CL) and visceral leishmaniasis (VL)
      caused by Leishmania braziliensis and Leishmania chagasi, respectively. METHODS:
      Drug activity was assessed against intracellular amastigotes by treating infected
      macrophage cultures and evaluating the number of infected cells. In vivo efficacy
      of tamoxifen was tested in L. braziliensis-infected BALB/c mice and in L. chagasi
      infected hamsters. Treatment with 20 mg/kg/day tamoxifen was administered for 15
      days by the intraperitoneal route. Efficacy was evaluated through measurements of
      lesion size, parasite burden at the lesion site or liver and spleen and survival
      rate. RESULTS: Tamoxifen killed L. braziliensis and L. chagasi intracellular
      amastigotes with 50% inhibitory concentrations (IC(50)) of 1.9 +/- 0.2 and 2.4 +/
      0.3 microM, respectively. Treatment of L. braziliensis-infected mice with
      tamoxifen resulted in significant reductions in lesion size and 99% decrease in
      parasite burden, compared with mock-treated controls. L. chagasi-infected
      hamsters treated with tamoxifen showed significant reductions in liver parasite
      load expressed as Leishman-Donovan units and 95% to 98% reduction in spleen
      parasite burden. All animals treated with tamoxifen survived while 100% of the
      mock-treated animals had died by 11 weeks after the interruption of treatment.
      CONCLUSIONS: Tamoxifen is effective in the treatment of CL and VL in rodent
      models.

PMID- 19095685
TI  - Reducing out-of-pocket expenditures to reduce poverty: a disaggregated analysis
      at rural-urban and state level in India.
AB  - Out-of-pocket (OOP) expenditure on health care has significant implications for
      poverty in many developing countries. This paper aims to assess the differential
      impact of OOP expenditure and its components, such as expenditure on inpatient
      care, outpatient care and on drugs, across different income quintiles, between
      developed and less developed regions in India. It also attempts to measure
      poverty at disaggregated rural-urban and state levels. Based on Consumer
      Expenditure Survey (CES) data from the National Sample Survey (NSS), conducted in
      1999-2000, the share of households' expenditure on health services and drugs was
      calculated. The number of individuals below the state-specific rural and urban
      poverty line in 17 major states, with and without netting out OOP expenditure,
      was determined. This also enabled the calculation of the poverty gap or poverty
      deepening in each region. Estimates show that OOP expenditure is about 5% of
      total household expenditure (ranging from about 2% in Assam to almost 7% in
      Kerala) with a higher proportion being recorded in rural areas and affluent
      states. Purchase of drugs constitutes 70% of the total OOP expenditure.
      Approximately 32.5 million persons fell below the poverty line in 1999-2000
      through OOP payments, implying that the overall poverty increase after accounting
      for OOP expenditure is 3.2% (as against a rise of 2.2% shown in earlier
      literature). Also, the poverty headcount increase and poverty deepening is much
      higher in poorer states and rural areas compared with affluent states and urban
      areas, except in the case of Maharashtra. High OOP payment share in total health
      expenditures did not always imply a high poverty headcount; state-specific
      economic and social factors played a role. The paper argues for better methods of
      capturing drugs expenditure in household surveys and recommends that special
      attention be paid to expenditures on drugs, in particular for the poor. Targeted
      policies in just five poor states to reduce OOP expenditure could help to prevent
      almost 60% of the poverty headcount increase through OOP payments.

PMID- 19095686
TI  - Long-QT syndrome and torsades de pointes in a patient with Takotsubo
      cardiomyopathy: an unusual case.
AB  - Takotsubo cardiomyopathy is a syndrome characterized by transient left
      ventricular apical ballooning associated with electrocardiogram (ECG) changes and
      minimal myocardial enzymatic release, mimicking acute myocardial infarction in
      patients without significant coronary disease at angiography. We report an
      unusual case of a patient who presented with Takotsubo cardiomyopathy associated
      with long-QT syndrome and who developed cardiac arrest secondary to torsades de
      pointes.The relationship between Takotsubo cardiomyopathy and abnormal
      repolarization has been well documented. Despite this, there have been few
      reports of malignant ventricular arrhythmias or sudden death. This report
      suggests that prolongation of QTc interval in Takotsubo cardiomyopathy may not be
      as benign as previously suggested but may in fact uncover an abnormality of
      repolarization that may be genetic in basis and carry a risk of sudden death.

PMID- 19095687
TI  - Induction of ventricular fibrillation rather than ventricular tachycardia
      predicts tachyarrhythmia recurrences in patients with idiopathic dilated
      cardiomyopathy and implantable cardioverter defibrillator for secondary
      prophylaxis.
AB  - AIMS: We sought to investigate the association of inducibility of polymorphic
      ventricular tachycardia or ventricular fibrillation (PVT/VF) or sustained
      monomorphic ventricular tachycardia (SMVT) at standardized programmed ventricular
      stimulation (PVS) with the long-term likelihood of sudden death and/or fast VT in
      a large cohort of patients with idiopathic non-ischaemic dilated cardiomyopathy
      (DCM) and implantable cardioverter defibrillator (ICD) for secondary prophylaxis.
      METHODS AND RESULTS: Between 1994 and 2007, 160 consecutive patients with DCM and
      spontaneous sustained VT/VF or cardiac arrest underwent PVS prior to ICD
      implantation. Outcome data, particularly probability of survival without (sudden)
      death or appropriate ICD therapies for fast VT, were assessed during long-term
      follow-up. PVT/VF was induced in 50 (31%) and SMVT in 30 (19%) patients. During a
      mean follow-up of 53 +/- 15 months, we observed 19/50 (38%), 10/30 (33%), and
      14/80 (18%) deaths in the PVT/VF, SMVT, and non-inducible group, respectively.
      These deaths were sudden in 7/50 (14%), 2/30 (7%), and 0/80 (0%) of patients,
      respectively. At least one fast VT was treated by the ICD in 26/50 (52%), 6/30
      (20%), and 22/80 (28%) patients, respectively. PVT/VF but not SMVT-inducible
      patients had a significantly worse overall survival (log-rank P = 0.013),
      survival without sudden cardiac death (P < 0.01), or survival without fast VT (P
      < 0.01) according to Kaplan-Meier method than non-inducible patients.
      Additionally, survival free of fast VT was significantly worse in PVT/VF vs. SMVT
      inducible patients (P < 0.01). CONCLUSION: Inducibility of PVT/VF is a much
      stronger predictor of recurrences of fast VT as opposed to SMVT induction in DCM
      patients with ICD for secondary prevention.

PMID- 19095688
TI  - Implantable cardioverter defibrillator lead diaphragmatic perforation.

PMID- 19095689
TI  - Spatial and temporal organization of the dominant frequencies in the fibrillating
      heart: body surface potential mapping in a rare case of sustained human
      ventricular fibrillation.
AB  - AIMS: The aim of this study was to assess the spatial and temporal variability of
      dominant fibrillation frequencies in a rare case of sustained human ventricular
      fibrillation (VF). METHODS AND RESULTS: Body surface potential mapping was
      performed in a patient with sustained VF and who was supported by a biventricular
      assist device. Dominant frequencies at 54 body sites were calculated from two
      recordings obtained 38 days apart. Variability of dominant frequencies between
      recordings and across body sites was quantified. Median dominant frequencies
      within recordings varied between 6.1 and 7.2 Hz in recording 1 and 5.6 and 6.6 Hz
      in recording 2, indicating a significant reduction in dominant frequencies
      between the recordings (P < 0.0001). Dominant frequencies differed across body
      sites by a mean (range) of 1.7 (0.4-2.8) Hz. CONCLUSION: In this rare case of
      sustained VF, there was significant spatial and temporal variability of VF
      dominant frequencies. These findings should be considered in future ECG studies
      on VF where the spatial variability of dominant frequency might not otherwise
      have been considered.

PMID- 19095690
TI  - Residual recipient right atrial tissue responsive to atropine 10 years following
      'bi-caval' orthotopic heart-lung transplantation.
AB  - A 51-year-old-man who had undergone a heart-lung transplant by 'bi-caval'
      anastomosis technique demonstrated residual recipient right atrial (RA)
      electrical activity responsive to muscarinic blockade 10 years after the surgery.
      The presumably initially denervated donor RA proved to be responsive to
      muscarinic blockade as well.

PMID- 19095691
TI  - Up-to-date catalogues of yeast protein complexes.
AB  - Gold standard datasets on protein complexes are key to inferring and validating
      protein-protein interactions. Despite much progress in characterizing protein
      complexes in the yeast Saccharomyces cerevisiae, numerous researchers still use
      as reference the manually curated complexes catalogued by the Munich Information
      Center of Protein Sequences database. Although this catalogue has served the
      community extremely well, it no longer reflects the current state of knowledge.
      Here, we report two catalogues of yeast protein complexes as results of
      systematic curation efforts. The first one, denoted as CYC2008, is a
      comprehensive catalogue of 408 manually curated heteromeric protein complexes
      reliably backed by small-scale experiments reported in the current literature.
      This catalogue represents an up-to-date reference set for biologists interested
      in discovering protein interactions and protein complexes. The second catalogue,
      denoted as YHTP2008, comprises 400 high-throughput complexes annotated with
      current literature evidence. Among them, 262 correspond, at least partially, to
      CYC2008 complexes. Evidence for interacting subunits is collected for 68
      complexes that have only partial or no overlap with CYC2008 complexes, whereas no
      literature evidence was found for 100 complexes. Some of these partially
      supported and as yet unsupported complexes may be interesting candidates for
      experimental follow up. Both catalogues are freely available at:
      http://wodaklab.org/cyc2008/.

PMID- 19095693
TI  - A feedback regulatory loop between methyltransferase PRMT1 and orphan receptor
      TR3.
AB  - PRMT1, an arginine methyltransferase, plays an important role in numerous
      cellular processes. In this study, we demonstrate a feedback regulatory loop
      between PRMT1 and the orphan receptor TR3. Unlike another orphan receptor HNF4,
      TR3 is not methylated by PRMT1 although they physically interact with each other.
      By delaying the TR3 protein degradation, PRMT1 binding leads to the elevation of
      TR3 cellular protein level, thereby enhances the DNA binding and transactivation
      activity of TR3 in a non-methyltransferase manner. Another coactivator SRC-2 acts
      synergistically with PRMT1 to regulate TR3 functions. In turn, TR3 binding to the
      catalytic domain of PRMT1 causes an inhibition of the PRMT1 methyltransferase
      activity. This repression results in the functional changes in some of PRMT1
      substrates, including STAT3 and Sam68. The negative regulation of PRMT1 by TR3
      was further confirmed in both TR3-knockdown cells and TR3-knockout mice with the
      use of an agonist for TR3. Taken together, our study not only identifies a
      regulatory role of PRMT1, independent on methyltransferase activity, in TR3
      transactivation, but also characterizes a novel function of TR3 in the repression
      of PRMT1 methyltransferase activity.

PMID- 19095692
TI  - Cellular versus viral microRNAs in host-virus interaction.
AB  - MicroRNAs (miRNAs) mark a new paradigm of RNA-directed gene expression regulation
      in a wide spectrum of biological systems. These small non-coding RNAs can
      contribute to the repertoire of host-pathogen interactions during viral
      infection. This interplay has important consequences, both for the virus and the
      host. There have been reported evidences of host-cellular miRNAs modulating the
      expression of various viral genes, thereby playing a pivotal role in the host
      pathogen interaction network. In the hide-and-seek game between the pathogens and
      the infected host, viruses have evolved highly sophisticated gene-silencing
      mechanisms to evade host-immune response. Recent reports indicate that virus too
      encode miRNAs that protect them against cellular antiviral response. Furthermore,
      they may exploit the cellular miRNA pathway to their own advantage. Nevertheless,
      our increasing knowledge of the host-virus interaction at the molecular level
      should lead us toward possible explanations to viral tropism, latency and
      oncogenesis along with the development of an effective, durable and nontoxic
      antiviral therapy. Here, we summarize the recent updates on miRNA-induced gene
      silencing mechanism, modulating host-virus interactions with a glimpse of the
      miRNA-based antiviral therapy for near future.

PMID- 19095694
TI  - Lymphadenovarix of the head-neck region--a rare presentation of Bancroftian
      filariasis.
AB  - Cystic swellings of the neck in children have limited differential diagnoses,
      often either lymphatic or vascular malformations. Other cystic inflammations can
      be the result of tuberculous abscesses, suppurated lymph nodes and actinomycosis.
      Microfilaria causing lmphadenovarix of head-neck region has not yet been
      described in the literature. A 10-year-old Indian boy presented with an
      asymptomatic cystic neck mass of 8 months duration. Aspiration of the swelling
      demonstrated numerous Wuchereria bancrofti microfilaria and the patient responded
      well to 6 weeks of daily anti-filarial treatment using diethylcarbamazine citrate
      (6mg kg(-1) day(-1)). This appears to be the first report of microfilariae
      associated lymphadenovarix of head-neck region. Though rare, filariasis should be
      considered as a differential diagnosis for aberrant swellings where lymphatic
      filarids are endemic.

PMID- 19095695
TI  - Psychotic disorder and extrapyramidal symptoms associated with vitamin B12 and
      folate deficiency.
AB  - Vitamin B12 and folate deficiency causing neuropsychiatric and thrombotic
      manifestations, such as peripheral neuropathy, subacute combined degeneration of
      cord, dementia, ataxia, optic atrophy, catatonia, psychosis, mood disturbances,
      myocardial infarction and portal vein thrombosis are well known. This present
      report highlights an unusual presentation of vitamin B12 deficiency-psychotic
      disorder, extrapyramidal symptoms in a 12-year-old boy. His symptoms responded to
      parenteral vitamin B12 therapy. So with this report we emphasized that serum
      vitamin B12 and folate levels should be measured, especially in those patients
      who present with other known neuropsychiatric features of vitamin B12 and folate
      deficiency.

PMID- 19095696
TI  - Calprotectin (a major S100 leucocyte protein) predicts 10-year radiographic
      progression in patients with rheumatoid arthritis.
AB  - BACKGROUND: Plasma levels of calprotectin, a major S100 leucocyte protein, are
      cross-sectionally associated with clinical and laboratory markers of inflammation
      and with radiographic damage in rheumatoid arthritis (RA). High amounts of
      calprotectin are found in synovial fluid from patients with RA. OBJECTIVE: To
      examine whether calprotectin might be an independent predictor of joint
      destruction over time. METHODS: 124 patients with RA were assessed at baseline
      and after 10 years with inflammatory markers (calprotectin, C-reactive protein
      (CRP), erythrocyte sedimentation rate (ESR)), serological variables (antibodies
      to cyclic citrullinated peptide (anti-CCP), IgA rheumatoid factor (RF) and IgM
      RF) and radiographic and clinical assessments of joint damage (hand radiographs
      and Rheumatoid Arthritis Articular Damage (RAAD) score). Progression of
      radiographic damage was assessed according to the van der Heijde modified Sharp
      score. RESULTS: At both examinations the highest calprotectin levels were found
      in patients positive for anti-CCP, IgA and IgM RF. Calprotectin had moderate to
      good correlations with inflammatory and serological markers (r = 0.41-0.67).
      Patients with normal baseline calprotectin levels had a lower degree of joint
      damage. High univariate associations were found between baseline calprotectin
      levels and progression in the Sharp score as well as the RAAD score. Baseline
      calprotectin was independently associated with progression in the Sharp score and
      with the RAAD score in multiple linear regression analyses, including baseline
      levels of CRP, ESR, anti-CCP in addition to demographic variables. CONCLUSION:
      Calprotectin was an independent predictor of clinical and radiographic joint
      damage after 10 years. These findings support the proposal that calprotectin may
      be a prognostic biomarker for erosive disease in patients with RA.

PMID- 19095697
TI  - Localization of O-glycans in MUC1 glycoproteins using electron-capture
      dissociation fragmentation mass spectrometry.
AB  - MUC1 is a mucin glycoprotein containing multiple tandem repeats of 20 amino
      acids, with five serines and threonines that can be O-glycosylated. Here, we
      investigated the O-glycosylation site occupancy in MUC1 glycoproteins produced in
      two mutant CHO cell lines, Lec3.2.8.1 and ldlD. We found that the average site
      occupancy was higher in MUC1 from Lec3.2.8.1 than from ldlD and that the
      occupancy increased with the number of tandem repeats in the protein and also
      depended on the culture conditions used for production. Moreover, we describe the
      successful use of electron-capture dissociation (ECD) fragmentation, coupled to
      online liquid chromatography mass spectrometry, to determine the glycosylation of
      individual sites in recombinant MUC1 proteins with 16 tandem repeats. We analyzed
      MUC1 tandem repeat peptides with 1-5 GalNAc residues by ECD fragmentation and
      found that the first site to be glycosylated was either Ser-5 or Thr-6, with the
      addition of a second GalNAc at Thr-14. For peptides with three GalNAc residues,
      several different variants of glycopeptides were found, indicating a
      heterogeneous order of glycosylation at this stage. In contrast, only one variant
      was found for peptides with four GalNAc residues, where Thr-19 in the PDTR motif
      was left unglycosylated, indicating that this site is glycosylated last. The
      results gave novel insight into the order of GalNAc substitution in MUC1 in vivo.

PMID- 19095698
TI  - Bidirectional N-acetylglucosamine transfer mediated by beta-1,4-N
      acetylglucosaminyltransferase III.
AB  - beta-1,4-N-Acetylglucosaminyltransferase III (GnT-III) catalyzes the formation of
      the bisecting GlcNAc and plays a regulatory role in the biosynthesis of the N
      linked oligosaccharide. In this study, we examined whether the glycosyl transfer
      catalyzed by GnT-III is reversible, and, in addition, investigated the
      equilibrium of the GnT-III-catalyzed reaction. Incubation of the agalactosyl
      bisected biantennary oligosaccharide with GnT-III in the presence of the
      sufficiently high concentration of uridine diphosphate (UDP) resulted in
      conversion of the bisected oligosaccharide into the nonbisected one. This
      reaction was accompanied by the stoichiometric formation of UDP-GlcNAc, which
      appeared to result from the transfer of GlcNAc from the oligosaccharide to UDP.
      Thus, these results indicate that GnT-III is capable of perceivably catalyzing
      the reverse reaction in vitro, as found in some glycosyltransferases. When the
      equilibrium of the reaction was kinetically analyzed, it was found that the state
      of the equilibrium is greatly displaced toward the formation of the bisecting
      GlcNAc. In terms of free energy change, as estimated, the reaction by GnT-III can
      be comparable to the hydrolysis of ATP. Although GnT-III catalyzes bidirectional
      transfer of GlcNAc between the oligosaccharide and UDP, the removal of the
      bisecting GlcNAc is unlikely in vivo, due to the displacement of the equilibrium.
      It is known that equilibria of certain glycosyltransferase reactions are not
      biased as greatly as the case of GnT-III, and thus it seems likely that there are
      a variety of equilibrium states in glycosyltransferase reactions. In living
      cells, the assembly of oligosaccharides could be regulated by not only rate
      control but also equilibrium control.

PMID- 19095699
TI  - Probabilistic assignment of formulas to mass peaks in metabolomics experiments.
AB  - MOTIVATION: High-accuracy mass spectrometry is a popular technology for high
      throughput measurements of cellular metabolites (metabolomics). One of the major
      challenges is the correct identification of the observed mass peaks, including
      the assignment of their empirical formula, based on the measured mass. RESULTS:
      We propose a novel probabilistic method for the assignment of empirical formulas
      to mass peaks in high-throughput metabolomics mass spectrometry measurements. The
      method incorporates information about possible biochemical transformations
      between the empirical formulas to assign higher probability to formulas that
      could be created from other metabolites in the sample. In a series of
      experiments, we show that the method performs well and provides greater insight
      than assignments based on mass alone. In addition, we extend the model to
      incorporate isotope information to achieve even more reliable formula
      identification. AVAILABILITY: A supplementary document, Matlab code, data and
      further information are available from
      http://www.dcs.gla.ac.uk/inference/metsamp.

PMID- 19095700
TI  - Prediction of RNA secondary structure using generalized centroid estimators.
AB  - MOTIVATION: Recent studies have shown that the methods for predicting secondary
      structures of RNAs on the basis of posterior decoding of the base-pairing
      probabilities has an advantage with respect to prediction accuracy over the
      conventionally utilized minimum free energy methods. However, there is room for
      improvement in the objective functions presented in previous studies, which are
      maximized in the posterior decoding with respect to the accuracy measures for
      secondary structures. RESULTS: We propose novel estimators which improve the
      accuracy of secondary structure prediction of RNAs. The proposed estimators
      maximize an objective function which is the weighted sum of the expected number
      of the true positives and that of the true negatives of the base pairs. The
      proposed estimators are also improved versions of the ones used in previous
      works, namely CONTRAfold for secondary structure prediction from a single RNA
      sequence and McCaskill-MEA for common secondary structure prediction from
      multiple alignments of RNA sequences. We clarify the relations between the
      proposed estimators and the estimators presented in previous works, and
      theoretically show that the previous estimators include additional unnecessary
      terms in the evaluation measures with respect to the accuracy. Furthermore,
      computational experiments confirm the theoretical analysis by indicating
      improvement in the empirical accuracy. The proposed estimators represent
      extensions of the centroid estimators proposed in Ding et al. and Carvalho and
      Lawrence, and are applicable to a wide variety of problems in bioinformatics.
      AVAILABILITY: Supporting information and the CentroidFold software are available
      online at: http://www.ncrna.org/software/centroidfold/.

PMID- 19095701
TI  - All hits all the time: parameter-free calculation of spaced seed sensitivity.
AB  - MOTIVATION: Standard search techniques for DNA repeats start by identifying small
      matching words, or seeds, that may inhabit larger repeats. Recent innovations in
      seed structure include spaced seeds and indel seeds which are more sensitive than
      contiguous seeds. Evaluating seed sensitivity requires (i) specifying a homology
      model for alignments and (ii) assigning probabilities to those alignments.
      Optimal seed selection is resource intensive because all alternative seeds must
      be tested. Current methods require that the model and its probability parameters
      be specified in advance. When the parameters change, the entire calculation has
      to be rerun. RESULTS: We show how to eliminate the need for prior parameter
      specification by exploiting a simple observation: given a homology model, the
      alignments hit by a particular seed remain the same regardless of the probability
      parameters. Only the weights assigned to those alignments change. Therefore, if
      we know all the hits, we can easily (and quickly) find optimal seeds. We describe
      an efficient preprocessing step, which is computed once per seed. Then we show
      several increasingly efficient methods to find the optimal seed when given
      specific probability parameters. Indeed, we show how to determine exactly which
      seeds can never be optimal under any set of probability parameters. This leads to
      the startling observation that out of thousands of seeds, only a handful have any
      chance of being optimal. We then show how to identify optimal seeds and the
      boundaries within probability space where they are optimal.

PMID- 19095702
TI  - Risk factors for work related injury among male farmers.
AB  - OBJECTIVE: To identify risk factors for serious farm work related injury among
      men. METHODS: A case-control study was conducted in Victoria, Australia. Eligible
      cases (n = 252) were males aged > or =16 years injured while working on a farm
      and scoring 2 or higher on the Abbreviated Injury Scale. Non-fatal injury cases
      were identified on presentation to hospital. Fatal cases (next of kin) were
      recruited via the Coroner's Office. Two age-matched controls per case were
      recruited by telephone. Data were collected with a structured telephone
      questionnaire. Logistic regression was used to compare risk factors between cases
      and controls, adjusting for design factors and average weekly hours worked.
      RESULTS: The most common external causes of injury were machinery (26%), falls
      (19%), transport (18%), animals (17%) and being struck by an object (11%).
      Increased injury risk was observed for being an employee/contractor (odds ratio
      1.8, 95% CI 1.2 to 2.7), not having attended farm training courses (1.5, 95% CI
      1.0 to 2.1), absence of roll-over protective structures on all/almost all
      tractors (2.5, 95% CI 1.7 to 3.8), absence of personal protective equipment for
      chemical use (4.7, 95% CI 1.6 to 13.9) and a low average annual farm income of
      AUD$5000 or less (2.7, 95% CI 1.3 to 5.6). Decreased injury risk was observed for
      several health related characteristics and some farm characteristics. CONCLUSION:
      We identified some risk factors possibly relevant to farm injury prevention
      programs. However, other factors were not associated with farm work injury
      suggesting these may not be as important as previously hypothesised.

PMID- 19095703
TI  - Modelling the non-linear multiple-lag effects of ambient temperature on mortality
      in Santiago and Palermo: a constrained segmented distributed lag approach.
AB  - OBJECTIVES: Exposure to ambient temperature can affect mortality levels for days
      or weeks following exposure, making modelling such effects in regression analysis
      of daily time-series data complex. METHODS: We propose a new approach involving a
      multi-lag segmented approximation to account for the non-linear effect of
      temperature and the use of two different penalized spline bases to model the
      distributed lag of both heat and cold exposure. Compared with standard splines,
      the novel penalized framework is more flexible at short lags where change in
      coefficients is greatest, and selection of the maximum lag appears substantially
      less important in determining the overall pattern of the effect. RESULTS:
      Applying the approach to daily mortality in Santiago (Chile) and Palermo (Italy),
      we observed a heat effect that was mostly immediate and followed by negative
      estimates consistent with short-term mortality displacement (harvesting). Cold
      effects were mostly positively sustained and more evenly distributed across the
      60-day analysis period: in Santiago we estimated an overall increase in deaths of
      2.36% (95% CI 0.26% to 4.51%) in the 65+ age group associated with every 1
      degrees C decrease below the cold threshold, and an increase of 1.11% (0.09% to
      2.14%) per 1 degrees C for Palermo. Heat effects for Palermo were much larger
      than for Santiago, and less harvesting of heat deaths was evident. The estimated
      heat thresholds were higher in Palermo than in Santiago. CONCLUSIONS: Our
      approach provides a flexible and precise method to quantify health effects of
      both heat and cold exposure at individual lags and to model the overall pattern
      of the delayed effect.

PMID- 19095704
TI  - Working for a healthier tomorrow.

PMID- 19095705
TI  - Research challenges in occupational and environmental medicine until 2030.

PMID- 19095706
TI  - Identifying research challenges for occupational and environmental medicine until
      2030: an initiative.

PMID- 19095707
TI  - Systematic review and meta-analysis of mortality in crop protection product
      manufacturing workers.
AB  - OBJECTIVES: The potential health effects of the manufacture and use of crop
      protection chemicals were investigated through systematic review and meta
      analysis of studies of cohorts of workers in the crop protection product
      manufacturing industry. METHODS: Several computerised literature databases were
      searched from inception until December 2003, with references listed in identified
      articles checked for further relevant articles. Random effects meta-analyses of
      log standardised mortality ratios (SMRs) were carried out. Heterogeneity was
      explored through subgroup analyses and meta-regression; sensitivity analyses of
      different approaches for zero events were performed. RESULTS: 21 references
      reporting information on 37 separate cohorts for mortality were identified. The
      meta-SMR for all cause mortality was 0.94 (95% CI 0.88 to 1.00) (37 cohorts).
      Significantly raised mortality was found for cancers of the buccal cavity and
      pharynx, oesophagus, rectum, larynx, lung, and lymphatic and haematopoietic
      system with little heterogeneity being observed. Excluding studies with zero
      events identified additional excesses. CONCLUSIONS: Evidence of multiple
      excesses, particularly in subgroups exposed to phenoxy herbicides contaminated
      with dioxins, substantiates previous findings. The importance of careful
      treatment of zero cases was highlighted. Future systematic reviews and meta
      analyses would benefit from availability of results for a standard list of causes
      of disease.

PMID- 19095708
TI  - Interpersonal conflicts at work as a predictor of self-reported health outcomes
      and occupational mobility.
AB  - OBJECTIVES: The aim of this prospective study was to examine the relationship
      between interpersonal conflicts at work and subsequent self-reported health
      outcomes (self-reported general health, need for recovery, and prolonged fatigue)
      and occupational mobility (internal mobility ie, changing job function, and
      external mobility ie, changing employers). METHODS: Data from the Maastricht
      Cohort Study on fatigue at work (n = 5582 for co-worker conflict; n = 5530 for
      supervisor conflict) were used. Interpersonal conflict with either co-workers or
      supervisors was assessed between baseline and 1-year follow-up. Outcomes were
      studied every 4 months between 1-year and 2-year follow-up. Logistic regression
      analyses using generalised estimating equations were conducted for each of the
      dichotomous outcomes, while controlling for demographic factors, the presence of
      a long-term illness, other workplace stressors, coping, and outcome at baseline.
      Analyses were conducted for men only. RESULTS: At baseline, conflicts with co
      workers occurred in 7.2% of the study population, while conflicts with
      supervisors occurred in 9.5% of the study population. In general, this study
      showed that co-worker conflict was a statistically significant risk factor for
      the onset of an elevated need for recovery, prolonged fatigue, poor general
      health and external occupational mobility. Supervisor conflict was a significant
      risk factor for the onset of an elevated need for recovery, prolonged fatigue,
      external occupational mobility, and internal occupational mobility. CONCLUSIONS:
      The results of this study indicate a possible causal relationship between
      interpersonal conflicts at work and self-reported health and occupational
      mobility. Given the considerable impact of interpersonal conflicts at work on the
      individual worker and on the organisation, and the fact that interpersonal
      conflicts at work are highly prevalent, these findings underline the need for
      interventions aimed at preventing the occurrence of interpersonal conflicts at
      work, or at least reducing the harmful effects on both the employee and the
      organisation.

PMID- 19095709
TI  - Pathological role of angiostatin in heart failure: an endogenous inhibitor of
      mesenchymal stem-cell activation.
AB  - OBJECTIVE: Recently, a clinical trial was initiated to evaluate the efficacy of
      transendocardial transplantation of autologous bone marrow-derived mesenchymal
      stem cells (MSC) for the treatment of heart failure (HF). Because some HF patient
      derived sera did not induce proliferation of autologous MSC, the present study
      aimed to elucidate humoral factors in sera that attenuate MSC activation and to
      investigate the role of these humoral factors in the pathogenesis of HF. METHODS
      AND RESULTS: Inhibitory effects present in serum were analysed by culturing human
      MSC with sera from 10 HF patients (FS <25%, BNP >100 pg/ml) and four healthy
      control subjects. Among the patients, two sera from HF patients showed
      significant inhibitory activity on MSC proliferation. Protein array and ELISA
      analysis revealed that these sera contained high levels of angiostatin as well as
      the active form of matrix metalloproteinase (MMP)-9, which generates angiostatin.
      Angiostatin significantly inhibited the proliferation and migration of cultured
      human MSC and increased their apoptosis in a dose-dependent manner. In a rat HF
      model, serum levels of angiostatin and MMPs increased, but treatment with an MMP
      inhibitor suppressed these increases. CONCLUSIONS: The results suggest that
      angiostatin, which can attenuate the activity of MSC, might play a role in the
      progression of HF.

PMID- 19095710
TI  - Appropriateness criteria: a useful tool for the cardiologist.

PMID- 19095711
TI  - Coronary heart disease epidemics: not all the same.
AB  - BACKGROUND: Coronary heart disease (CHD) was an important epidemic in many
      developed countries in the 20th century and there is concern because the epidemic
      has affected Eastern Europe, Russia and Central Asia and is starting to affect
      developing countries. METHODS: The epidemic curves of CHD mortality for 55
      countries, which had reliable data and met other selection criteria, were
      examined using age-standardised death rates 35-74 years from the World Health
      Organization. Annual male mortality rates for individual countries from 1950 to
      2003 were plotted and a table and a graph used to classify countries by
      magnitude, pattern and timing of its CHD epidemic. RESULTS: The natural history
      of CHD epidemics varies markedly among countries. Different CHD patterns are
      distinguishable including "rise and fall" (classic epidemic pattern), "rising"
      (first part of epidemic) and "flat" (no epidemic yet). Furthermore, epidemic
      peaks were higher in Anglo-Celtic countries first affected by the epidemic, and
      subsequent peaks were less, except for the recent extraordinary epidemics in
      Russia and Central Asian republics. There were considerable differences among
      some continental or regional geographical areas. Eastern European, South American
      and Asian countries have quite different epidemic characteristics, including
      shorter epidemic cycles. CONCLUSIONS: It cannot be assumed that WHO regions or
      any other geographical regions will be useful when analysing CHD epidemics or
      deciding upon strategic policies to reduce CHD in individual countries. The needs
      for action that are urgent in some countries are less so in others, and even
      regional country groups can have quite different epidemic characteristics.

PMID- 19095712
TI  - Left ventricular long axis dysfunction in adults with "corrected" aortic
      coarctation is related to an older age at intervention and increased aortic
      stiffness.
AB  - OBJECTIVES: This study examined the prevalence of left ventricular (LV) long axis
      dysfunction (LAD, septal annulus pulsed-wave (PW) tissue Doppler imaging (TDI)
      early diastolic velocity < or =8 cm/s) in patients with "corrected" aortic
      coarctation and its relationship to patient demographics and aortic elastic
      properties. METHODS: A retrospective study of 80 consecutive patients with
      "corrected" aortic coarctation (aged 27 (SD 6) years, seven postballoon
      aortoplasty, 41 poststenting and 32 postsurgical repair) was carried out.
      Patients' ages at intervention, comorbidities and medications were recorded. The
      LV long axis motions were recorded by M-mode and PW TDI. Aortic stiffness indices
      were calculated from the aortic diameters and pulse pressures. RESULTS: Forty
      seven patients (59%) had LAD. They were older (28 (5) vs 9 (6) years) at
      treatment, had stiffer aorta (stiffness index 18.4 (6.0) vs 9.2 (2.3)), thicker
      LV walls (146.7 (59.7) vs 103.8 (44.9) g/m2), higher wall stress (80 (6) vs 70
      (7) 10(3) dynes/cm2), larger left atria (31.7 (4.6) vs 24.5 (5.3) ml/m2) and
      higher LV filling pressures (p<0.01 for all) compared with those without LAD,
      despite a similar prevalence of antihypertensive use and bicuspid aortic valves.
      The age at intervention (OR 2.92, 95% CI 1.29 to 6.60, p<0.01) and aortic
      stiffness index (OR 1.98, 95% CI 1.41 to 2.79, p<0.001) were the two independent
      predictors for LAD in patients on multivariate analysis. A cut-off age of > or
      =25 year at intervention was 89% sensitive and 76% specific in predicting LAD
      (AUC = 0.90, p<0.001). CONCLUSIONS: LAD is common in adults with aortic
      coarctation despite apparently successful treatment. Its presence is related to
      older age at intervention and increased aortic stiffness.

PMID- 19095713
TI  - Angiostatin: drying out the roots in cardiac muscle.

PMID- 19095714
TI  - Cost-effectiveness of radiofrequency catheter ablation for the treatment of
      atrial fibrillation in the United Kingdom.
AB  - OBJECTIVE: To assess the cost-effectiveness of radiofrequency catheter ablation
      (RFCA) compared with anti-arrhythmic drug (AAD) therapy for the treatment of
      atrial fibrillation (AF) from the perspective of the UK NHS. DESIGN: Bayesian
      evidence synthesis and decision analytical model. METHODS: A systematic review
      and meta-analysis was conducted and Bayesian statistical methods used to
      synthesise the effectiveness evidence from randomised control trials. A decision
      analytical model was developed to assess the costs and consequences associated
      with the primary outcome of the trials over a lifetime time horizon. MAIN OUTCOME
      MEASURE: Costs from a health service perspective and outcomes measured as quality
      adjusted life years (QALYs). RESULTS: The incremental cost-effectiveness ratio of
      RFCA varied between pound7763 and pound7910 for each additional QALY according to
      baseline risk of stroke, with a probability of being cost-effective from 0.98 to
      0.99 for a cost-effectiveness threshold of pound20 000. Results were sensitive to
      the duration of quality of life benefits from treatment. CONCLUSIONS: RFCA is
      potentially cost-effective for the treatment of paroxysmal AF in patients'
      predominantly refractory to AAD therapy provided the quality-of-life benefits
      from treatment are maintained for more than 5 years. These findings remain
      subject to limitations in the existing evidence regarding the nature of life
      benefits and the prognostic importance of restoring normal sinus rhythm conferred
      using RFCA.

PMID- 19095715
TI  - Putting research in context: understanding confidence intervals from one or more
      studies.
AB  - OBJECTIVES: To support wider use and higher quality interpretation of confidence
      intervals (CIs) in psychology. METHODS: We discuss the meaning and interpretation
      of CIs in single studies, and illustrate the value of CIs when reviewing and
      integrating research findings across studies. We demonstrate how to find CIs from
      summary statistics and published data in some simple situations. RESULTS: We
      provide the ESCI graphical software, which runs under Microsoft Excel, to assist
      with calculating and plotting CIs. (www.latrobe.edu.au/psy/esci) CONCLUSIONS: The
      wider use of CIs in psychology should support quality research communication and
      integrated interpretation of findings in context.

PMID- 19095716
TI  - Telomere elongation involves intra-molecular DNA replication in cells utilizing
      alternative lengthening of telomeres.
AB  - Alternative lengthening of telomeres (ALT) is a telomere length maintenance
      mechanism based on recombination, where telomeres use other telomeric DNA as a
      template for DNA synthesis. About 10% of all human tumors depend on ALT for their
      continued growth, and understanding its molecular details is critically important
      for the development of cancer treatments that target this mechanism. We have
      previously shown that telomeres of ALT-positive human cells can become lengthened
      via inter-telomeric copying, i.e. by copying the telomere of another chromosome.
      The possibility that such telomeres could elongate by using other sources of
      telomeric DNA as copy templates has not been investigated previously. In this
      study, we have determined whether a telomere can become lengthened by copying its
      own sequences, without the need for using another telomere as a copy template. To
      test this, we transduced an ALT cell line with a telomere-targeting construct and
      obtained clones with a single tagged telomere. We showed that the telomere tag
      can be amplified without the involvement of other telomeres, indicating that
      telomere elongation can also occur by intra-telomeric DNA copying. This is the
      first direct evidence that the ALT mechanism involves more than one method of
      telomere elongation.

PMID- 19095717
TI  - Mechanisms of formation and accumulation of mitochondrial DNA deletions in aging
      neurons.
AB  - Age-dependent accumulation of partially deleted mitochondrial DNA (DeltamtDNA)
      has been suggested to contribute to aging and the development of age-associated
      diseases including Parkinson's disease. However, the molecular mechanisms
      underlying the generation and accumulation of DeltamtDNA have not been addressed
      in vivo. In this study, we have developed a mouse model expressing an inducible
      mitochondria-targeted restriction endonuclease (PstI). Using this system, we
      could trigger mtDNA double-strand breaks (DSBs) in adult neurons. We found that
      this transient event leads to the generation of a family of DeltamtDNA with
      features that closely resemble naturally-occurring mtDNA deletions. The formation
      of these deleted species is likely to be mediated by yet uncharacterized DNA
      repairing machineries that participate in homologous recombination and non
      homologous end-joining. Furthermore, we obtained in vivo evidence that
      DeltamtDNAs with larger deletions accumulate faster than those with smaller
      deletions, implying a replicative advantage of smaller mtDNAs. These findings
      identify DSB, DNA repair systems and replicative advantage as likely mechanisms
      underlying the generation and age-associated accumulation of DeltamtDNA in
      mammalian neurons.

PMID- 19095718
TI  - A translational approach to myocardial remodelling.

PMID- 19095719
TI  - Long-term outcomes of patients receiving drug-eluting stents.
AB  - BACKGROUND: We sought to establish the long-term safety of drug-eluting stents
      compared with bare-metal stents in a usual care setting. METHODS: Using data from
      a prospective multicentre registry, we compared rates of death and of death or
      repeat revascularization during 3 years of follow-up of 6440 consecutive patients
      who underwent angioplasty with either drug-eluting or bare-metal stents between
      Apr. 1, 2003, and Mar. 31, 2006. RESULTS: Drug-eluting stents were inserted in
      1120 patients and bare-metal stents in 5320. The drug-eluting stents were
      selected for patients who had a greater burden of comorbid illness, including
      diabetes mellitus (32.8% v. 20.8% in the bare-metal group, p < 0.001) and renal
      disease (7.4% v. 5.0%, p = 0.001). At 1-year follow-up, the drug-eluting stents
      were associated with a mortality of 3.0%, as compared with 3.7% with the bare
      metal stents (adjusted odds ratio [OR] 0.62, 95% confidence interval [CI] 0.46
      0.83). The rate of the composite outcome of death or repeat revascularization was
      12.0% for the drug-eluting stents and 15.8% for the bare-metal stents (adjusted
      OR 0.40, 95% CI 0.33-0.49). In the subgroup of patients who had acute coronary
      syndromes, the adjusted OR for this composite outcome was 0.46 (95% CI 0.35
      0.61). During the 3 years of observation, the relative risks for death and repeat
      revascularization varied over time. In year 1, there was an initial period of
      lower risk in the group with drug-eluting stents than in the group with bare
      metal stents; this was followed by a shift toward outcome rates favouring bare
      metal stents in years 2 and 3. The adjusted relative risk of the composite
      outcome of death or repeat revascularization associated with drug-eluting stents
      relative to bare-metal stents was 0.73 early in the first year of follow-up; it
      then rose gradually over time, to a peak of 2.24 at 3 years. INTERPRETATION: Drug
      eluting stents are safe and effective in the first year following insertion.
      Thereafter, the possibility of longer term adverse events cannot be ruled out.

PMID- 19095721
TI  - Medical injury compensation: beyond 'no-fault'.

PMID- 19095720
TI  - Pinoline may be used as a probe for CYP2D6 activity.
AB  - Pinoline, 6-methoxy-1,2,3,4-tetrahydro-beta-carboline, is a serotonin analog that
      selectively inhibits the activity of monoamine oxidase-A and shows antidepressant
      activity. Our previous study using a panel of recombinant cytochrome P450 (P450)
      enzymes suggests that pinoline O-demethylation may be selectively catalyzed by
      polymorphic CYP2D6. The current study, therefore, aimed to delineate the impact
      of CYP2D6 status on pinoline metabolism. Enzyme kinetic studies using recombinant
      CYP2D6 allelic isozymes revealed that CYP2D6.2 exhibited 5-fold lower enzyme
      efficiency (V(max)/K(m)) toward pinoline compared with CYP2D6.1, and CYP2D6.10
      did not show any catalytic activity. Inhibition study showed that quinidine (1
      microM) completely blocked pinoline O-demethylase activity in human liver
      microsomes, whereas other P450 isoform-selective inhibitors had no or minimal
      effects. Pinoline O-demethylase activities in 10 human liver microsomes showed
      significantly strong correlation with bufuralol 1'-hydroxylase activities
      (R(2)=0.93; p<0.0001) and CYP2D6 contents (R(2)=0.82; p=0.005), whereas no
      appreciable correlations with enzymatic activities of other P450 enzymes were
      found. Furthermore, we compared pinoline urinary metabolic ratio (pinoline/6
      hydroxy-1,2,3,4-tetrahydro-beta-carboline) between CYP2D6-humanized and wild-type
      control mice after intraperitoneal injection of pinoline (30 mg/kg). Results
      indicated that the two genotyped mice were clearly distinguished by pinoline
      metabolic ratio (mean +/- S.D.), which was much higher in wild-type mice (0.29+/
      0.19, n=4) than in CYP2D6-humanized transgenic mice (0.0070+/-0.0048, n=4). Our
      findings suggest that pinoline O-demethylation is governed by CYP2D6 status, and
      pinoline, at a proper concentration or dose, may be a good probe to evaluate
      CYP2D6 activity.

PMID- 19095722
TI  - On the materiality of risk: paper tigers and panaceas.

PMID- 19095723
TI  - C-reactive protein: eighty years from discovery to emergence as a major risk
      marker for cardiovascular disease.

PMID- 19095724
TI  - Inhibition of endothelial nitric oxide synthase by C-reactive protein: clinical
      relevance.

PMID- 19095726
TI  - Tracking of high-sensitivity C-reactive protein after an initially elevated
      concentration: the JUPITER Study.
AB  - BACKGROUND: The JUPITER (Justification for the Use of Statins in Prevention: An
      Intervention Trial Evaluating Rosuvastatin) trial suggests that increased high
      sensitivity C-reactive protein (hsCRP) concentrations may be useful in decisions
      about the initiation of statin therapy for primary prevention of vascular
      disease. Although studies of specific populations have suggested that hsCRP is a
      reliable longitudinal marker, it is unclear how strongly hsCRP tracks in
      individuals after a single increased concentration. METHODS: We evaluated
      tracking of hsCRP in 8901 individuals randomized to placebo in the JUPITER trial.
      These individuals had screening LDL cholesterol concentrations <130 mg/dL (<3.37
      mmol/L) and hsCRP concentrations > or =2 mg/L, with subsequent hsCRP measurements
      made before randomization; at 13 weeks; 1, 2, 3, and 4 years later; and at trial
      termination. Longitudinal trends and associations were evaluated
      nonparametrically with box plots and Spearman correlations. After data
      transformation to achieve normality, repeated-measures regression models
      estimated the intraclass correlation of hsCRP, with and without controlling for
      known demographic, lifestyle, and medical determinants of hsCRP concentration.
      For comparison, we evaluated tracking of systolic and diastolic blood pressure;
      total, LDL, and HDL cholesterol; and fasting triglycerides. RESULTS: The median
      hsCRP concentration in these untreated individuals showed modest regression to
      the mean over time, declining from 3.8 mg/L at randomization to 3.4 mg/L at 4
      years. Tracking correlations for hsCRP over time were comparable to those for
      blood pressure and LDL cholesterol, but lower than those for HDL, fasting
      triglycerides, and total cholesterol. The intraclass correlation for repeated
      hsCRP measurements was 0.54 (95% CI, 0.53-0.55) without covariate adjustment and
      0.50 (95% CI, 0.49-0.51) after adjustment for demographic, lifestyle, and
      comorbidity determinants. CONCLUSIONS: Concentrations of hsCRP show strong
      tracking, even after selection of individuals with initially high values. Without
      statin therapy, increased concentrations of hsCRP generally remain high over
      time.

PMID- 19095725
TI  - Relation of genetic variation in the gene coding for C-reactive protein with its
      plasma protein concentrations: findings from the Women's Health Initiative
      Observational Cohort.
AB  - BACKGROUND: Although common genetic variants of the CRP gene (C-reactive protein,
      pentraxin related) have been associated with plasma concentrations of high
      sensitivity CRP (hsCRP) in several cohorts of European Americans, relatively few
      studies have comprehensively assessed this association in well-characterized
      multiethnic populations. METHODS: In a case-control study of diabetes nested in
      the Women's Health Initiative Observational Cohort, we comprehensively evaluated
      the association of genetic variation in CRP with plasma hsCRP concentrations.
      Thirteen haplotype-tagging single-nucleotide polymorphisms (tSNPs) were
      identified and subsequently genotyped in 3782 postmenopausal women. RESULTS: The
      allele frequencies for these tSNPs and the haplotype blocks defined by these
      tSNPs varied significantly by ethnic group (P < 0.0001). Consistent with prior
      studies of whites, rs3093068, rs1130864, and rs1417938 were significantly
      associated with higher hsCRP concentrations (geometric-mean increase per minor
      allele change, 1.20-1.25 mg/L), and rs1205 and rs1800947 were significantly
      associated with lower hsCRP values (decrease of 1.28-1.48 mg/L). The associations
      with rs3093068 and rs1205 appeared to be stronger in Asians/Pacific Islanders
      than in whites (geometric-mean increase, 1.65 mg/L vs 1.25 mg/L, respectively).
      Minor alleles at rs3093075 and rs3093059 were associated with substantially
      increased hsCRP concentrations, whereas rs1800947 was associated with lower hsCRP
      values. All haplotype-based association results tended to be consistent with the
      associations seen with single CRP SNPs. CONCLUSIONS: Our large multiethnic case
      control study of postmenopausal women provides evidence that common genetic
      variants in the CRP gene are substantially associated with plasma hsCRP
      concentrations in this case-control subcohort. The data also suggest ethnic
      variations in these associations.

PMID- 19095727
TI  - High-sensitivity C-reactive protein and cardiovascular disease.

PMID- 19095728
TI  - Concentrations of C-reactive protein and B-type natriuretic peptide 30 days after
      acute coronary syndromes independently predict hospitalization for heart failure
      and cardiovascular death: just another brick in the wall?

PMID- 19095729
TI  - Determinants of the acute-phase protein C-reactive protein in myocardial
      infarction survivors: the role of comorbidities and environmental factors.
AB  - BACKGROUND: C-reactive protein (CRP), a sensitive marker of the acute-phase
      response, has been associated with future cardiovascular endpoints independently
      of other risk factors. A joint analysis of the role of risk factors in predicting
      mean concentrations and variation of high-sensitivity CRP (hsCRP) in serum has
      not been carried out previously. METHODS: We used data from 1003 myocardial
      infarction (MI) survivors who had hsCRP measured monthly up to 8 times and
      multivariate mixed effects statistical models to study the role of time-variant
      and -invariant factors on the geometric mean of and the intraindividual variation
      in hsCRP concentrations. RESULTS: Patients with > or =6.5% glycosylated
      hemoglobin (HbA1c) had 26.2% higher hsCRP concentrations (95% CI, 7.2%-48.6%) and
      20.7% greater variation in hsCRP values (P = 0.0034) than patients with lower
      baseline Hb A(1c) values (<6.5%). Similar but less pronounced differences were
      seen in patients with a self-reported diagnosis of type 2 diabetes. hsCRP
      concentrations showed less variation in patients who reported angina pectoris,
      congestive heart failure, or emphysema (-11.0%, -24.9%, and -41.6%, respectively,
      vs patients without these conditions) but greater variation in males and smokers
      (+24.8% and +27.3%, respectively, vs females and nonsmokers). Exposures in the 24
      h before blood sampling, including exposure to environmental tobacco smoke,
      alcohol consumption, and extreme stress, did not have a major impact.
      CONCLUSIONS: One or 2 hsCRP measurements may not be sufficient to adequately
      characterize different patient groups after MI with similar precisions. We found
      hsCRP concentrations to be especially variable in males, smokers, and patients
      with increased Hb A(1c) values.

PMID- 19095730
TI  - The clinical utility of high-sensitivity C-reactive protein in cardiovascular
      disease and the potential implication of JUPITER on current practice guidelines.
AB  - BACKGROUND: High-sensitivity C-reactive protein (hsCRP) testing is relatively
      inexpensive and has been shown to predict the risk of cardiovascular disease
      (CVD) and diabetes in multiple patient groups, including those treated with
      statin therapy. JUPITER (Justification for the Use of Statins in Primary
      Prevention: An Intervention Trial Evaluating Rosuvastatin) is a recently
      completed large multicenter randomized clinical trial that tested whether statin
      therapy should be given to apparently healthy individuals with lower LDL
      cholesterol (LDL-C) concentrations but increased hsCRP concentrations. CONTENT:
      This review discusses the literature on hsCRP in asymptomatic populations,
      analyzes it according to CVD and diabetes, and provides summary recommendations
      for the use of hsCRP in clinical practice. In this context, we highlight recent
      data from the landmark JUPITER trial, which demonstrated that hsCRP can be used
      to target high-risk patients who have typical LDL-C concentrations and no known
      vascular disease or diabetes and who would benefit from statin use. We also
      summarize evidence that among patients treated with statin therapy, achieving low
      hsCRP concentrations may be a clinically relevant therapeutic goal along with
      achieving very low LDL-C concentrations. SUMMARY: JUPITER has demonstrated that
      combining hsCRP testing with traditional testing of lipids can reduce incident
      CVD in high-risk asymptomatic individuals by 44% and all-cause mortality by
      approximately 20%, extending the therapeutic use of statins for the primary
      prevention of CVD. Guidelines for practitioners could include testing
      asymptomatic individuals for increased concentrations of hsCRP in men > or =50
      years and women > or =60 years when LDL-C concentrations are not increased and
      for whom the decision to treat with statin therapy is not otherwise clear.

PMID- 19095732
TI  - A carbon monoxide-releasing molecule (CORM-3) exerts bactericidal activity
      against Pseudomonas aeruginosa and improves survival in an animal model of
      bacteraemia.
AB  - The search for new molecules to fight Pseudomonas aeruginosa is of paramount
      importance. Carbon monoxide (CO) is known to act as an effective inhibitor of the
      respiratory chain in P. aeruginosa, but the practical use of this gas as an
      antibacterial molecule is hampered by its toxicity and difficulty to manipulate.
      Here, we show that a water-soluble CO releaser (CORM-3) possesses bactericidal
      properties against laboratory and antibiotic-resistant P. aeruginosa. CORM-3
      reduced the bacterial count by 4 logs 180 min after in vitro treatment. CORM-3
      treated bacteria had a lower O(2) consumption than vehicle-treated bacteria, and
      the decrease in O(2) consumption temporally preceded the bactericidal action of
      CORM-3. These results support the hypothesis that the antimicrobial effect of
      CORM-3 is mediated by an interaction of CO liberated by the carrier with the
      bacterial respiratory chain. The antibacterial effect occurred at concentrations
      of CORM-3 that are 50-fold lower than toxic concentrations for eukaryotic cells.
      CORM-3 treatment compared to vehicle treatment decreased bacterial counts in the
      spleen and increased survival in immunocompetent and immunosuppressed mice
      following P. aeruginosa bacteremia. Our results suggest that CORMs could form the
      basis for developing a new therapeutic strategy against P. aeruginosa-induced
      infection.

PMID- 19095731
TI  - The evolving role of C-reactive protein in atherothrombosis.
AB  - BACKGROUND: Inflammation is pivotal in all phases of atherosclerosis. Among the
      numerous inflammatory biomarkers, the largest amount of published data supports a
      role for C-reactive protein (CRP) as a robust and independent risk marker in the
      prediction of primary and secondary adverse cardiovascular events. In addition to
      being a risk marker, there is much evidence indicating that CRP may indeed
      participate in atherogenesis. CONTENT: In this review, we focus on the role of
      CRP in promoting atherothrombosis by discussing its effects on endothelial cells,
      endothelial progenitor cells, monocyte-macrophages, and smooth muscle cells.
      CONCLUSIONS: CRP is clearly a risk marker for cardiovascular disease and is
      recommended for use in primary prevention. In addition, CRP appears also to
      contribute to atherogenesis. However, much further research is needed, especially
      in appropriate animal models, to confirm the possible role of CRP in promoting
      atherothrombosis.

PMID- 19095733
TI  - The magnitude and temporal dependence of apoptosis early after myocardial
      ischemia with or without reperfusion.
AB  - In view of the conventional wisdom in the cardiology literature that apoptosis is
      extensive early after myocardial ischemia, predicated largely from results with
      the TUNEL assay known to be nonspecific, this study was performed to delineate
      its extent with multiple assays and at multiple intervals. Coronary occlusion
      with and without subsequent revascularization was induced in 10-wk-old C57BL6
      mice subjected to 1 or 4 h of transient ligation followed by 24 h of reperfusion,
      or 24 h persistent ligation. Apoptosis was quantified throughout the left
      ventricle immunohistochemically by assay of TUNEL, single-stranded DNA (ssDNA),
      and cleaved caspase 3; electron microscopy (EM); and activity assays of caspase 3
      and 8. TUNEL staining was marked, but ssDNA and cleaved caspase 3 staining were
      significantly less (P<0.001 compared with TUNEL), and apoptosis defined by EM was
      virtually absent in all groups. Caspase 3 and caspase 8 activities per milligram
      protein were not significantly different from those in normal hearts. Only rare,
      potentially apoptotic cells were seen by EM in hearts from any group. Thus, the
      results with TUNEL were not specific, and the extent of apoptosis was markedly
      less than that predicated on the results with the TUNEL procedure. Apoptosis is
      de minimus early after transitory or persistent ischemia, though it is
      overestimated by TUNEL assays. Thus, antiapoptotic interventions per se are not
      likely to preserve substantial amounts of myocardium early after ischemic
      insults.

PMID- 19095734
TI  - Inhibition of spontaneous neutrophil apoptosis by parabutoporin acts
      independently of NADPH oxidase inhibition but by lipid raft-dependent stimulation
      of Akt.
AB  - Neutrophil cell death plays a crucial role in neutrophil homeostasis and the
      resolution of inflammation. The superoxide-producing NADPH oxidase is involved in
      pathogen degradation and subsequent activation of cell death programs.
      Neutrophils from patients with chronic granulomatous disease, who have a
      deficient NADPH oxidase activity, have been demonstrated previously to have a
      prolonged lifespan, suggesting that a basal NADPH oxidase activity also regulates
      spontaneous neutrophil turnover. The NADPH oxidase inhibitor parabutoporin (PP)
      does delay spontaneous apoptosis, but this effect is completely independent of
      NADPH oxidase inhibition. Instead, the prosurvival effect of PP depends on
      activation of protein kinase B/Akt via lipid raft signaling. Disruption of lipid
      rafts abrogates the prosurvival effect without interfering with NADPH oxidase
      activity. Furthermore, we cannot detect a different rate of spontaneous apoptosis
      between normal and NADPH oxidase-deficient neutrophils, arguing against a role of
      NADPH oxidase in spontaneous neutrophil apoptosis.

PMID- 19095735
TI  - Antigen-independent adhesion and cell spreading by inducible costimulator
      engagement inhibits T cell migration in a PI-3K-dependent manner.
AB  - Engagement of the costimulatory protein ICOS activates effector/memory T cells in
      tissue by enhancing TCR-mediated proliferation and cytokine production. We now
      report that in an antigen-independent manner, ICOS also induces adhesion and
      spreading in human effector/memory T cells, consequently inhibiting cell
      migration. T cell spreading and elongation after ICOS ligation are accompanied by
      the formation of two types of actin-rich membrane protrusions: thin, finger-like
      structures similar to filopodia and short, discrete microspikes. Although
      filopodia/microspike formation occurs independently of the PI-3K signaling
      cascade, ICOS-mediated T cell elongation depends on PI-3K activity, which
      inhibits the accumulation of GTP-bound RhoA. Further inhibition of RhoA
      activation exacerbates the ICOS-mediated, elongated phenotype. We propose that in
      inflamed tissue, ICOS engagement by ICOS ligand on a professional or
      nonprofessional APC prevents the forward motility of the T cell by inhibiting
      RhoA-dependent uropod retraction. The resulting ICOS-induced T cell spreading and
      filopodia/microspike formation may promote antigen recognition by enhancing a T
      cell's scanning potential of an adherent APC surface.

PMID- 19095736
TI  - Adenosine and IFN-{alpha} synergistically increase IFN-gamma production of human
      NK cells.
AB  - Prevention of overwhelming immune reactions is essential for an organism to
      survive. Adenosine, a ribonucleoside produced by various cell types during
      inflammatory processes, has been shown to inhibit effector functions of different
      immune cells. Here, we show that the adenosine A(3) receptor agonist iodobenzyl
      methylcarboxamidoadenosine potently inhibited proliferation, IFN-gamma
      production, and cytotoxicity of activated human lymphoid cells. Stimulation of
      the A(3) receptor also caused apoptosis of activated PBMC. However, when PBMC
      were stimulated with IFN-alpha, adenosine did not decrease, but synergistically
      increased, the IFN-gamma production of NK cells. This effect was also mediated
      mainly via the A(3) receptor. Thus, our data suggest that adenosine
      differentially contributes to the regulation of immune responses during
      inflammatory processes: It may increase effector functions of NK cells in
      combination with IFN-alpha but also prevents overwhelming immune responses by
      inhibiting proliferation and induction of apoptosis of activated lymphoid cells.
      Future studies need to define the role of the different adenosine receptors in
      more detail.

PMID- 19095737
TI  - Activation of insulin-like growth factor II receptor induces mitochondrial
      dependent apoptosis through G(alpha)q and downstream calcineurin signaling in
      myocardial cells.
AB  - In previous studies, we have found that IGF-II and IGF-II receptor (IGF-IIR) dose
      dependently correlated with the progression of pathological hypertrophy after
      complete abdominal aorta ligation, which may play a critical role in angiotensin
      II-induced cardiomyocyte apoptosis. However, the detail mechanisms of IGF-IIR in
      the regulation of cell apoptosis in response to IGF-II remain unclear. By using
      IGF-IR short hairpin RNA to inhibit IGF-IR expression and using Leu27 IGF-II
      analog to activate specifically the IGF-IIR, we investigated the role of IGF
      II/IGF-IIR activation and its downstream signaling. Our results revealed that IGF
      II synergistically increased the cell apoptosis induced by suppressing of IGF-IR
      in neonatal rat ventricular myocytes. After binding of Leu27IGF-II, IGF-IIR
      became associated with alpha-q polypeptide, acted like a protein-coupled receptor
      to activate calcineurin, led to the translocation of Bad into mitochondria and
      release of cytochrome c into cytoplasm, and contributed to mitochondrial
      dependent apoptosis in neonatal rat ventricular myocytes. Furthermore, inhibition
      of IGF-IIR, alpha-q polypeptide, or calcineurin by RNA interference could block
      the Leu27IGF-II-induced cell apoptosis. Together, this study provides a new
      insight into the effects of the IGF-IIR and its downstream signaling in
      myocardial apoptosis. Suppression of IGF-IIR signaling pathways may be a good
      strategy for both the protection against myocardial cell apoptosis and the
      prevention of heart failure progression.

PMID- 19095738
TI  - Inflammatory cytokines regulate glycoprotein subunit beta5 of thyrostimulin
      through nuclear factor-kappaB.
AB  - Thyrostimulin is a heterodimeric hormone comprised of two glycoprotein hormone
      subunits, namely glycoprotein hormone subunit alpha2 and glycoprotein hormone
      subunit beta5 (GPB5). Immunological studies have revealed that both subunits
      colocalize in human pituitary corticotroph cells. Although recombinant
      thyrostimulin protein selectively activates the TSH receptor and has thyrotropic
      activity in rats, its biological functions have not been clarified. To explore
      the physiological regulators for the GPB5, the 5'-flanking region of the GPB5
      coding sequence up to 3-kb upstream was analyzed by luciferase reporter assays.
      We found that nuclear factor-kappaB (NF-kappaB) markedly activated GPB5
      transcription. Disruption of the putative NF-kappaB-binding motifs in the GPB5 5'
      flanking region silenced the GPB5 activation by p65. Chromatin
      immunoprecipitation assays revealed that recombinant p65 bound to the predicted
      NF-kappaB-binding sites. Because NF-kappaB is known to associate with acute phase
      inflammatory cytokines, we examined whether TNFalpha or IL-1beta could regulate
      GPB5. Both these cytokines activated GPB5 transcription by 2- to 3-fold, and
      their effects were abolished by the addition of MG132, a NF-kappaB inhibitor. Our
      results suggest that inflammatory cytokines positively regulate thyrostimulin
      through NF-kappaB activation.

PMID- 19095739
TI  - Expression pattern of G protein-coupled receptor 30 in LacZ reporter mice.
AB  - Multiple reports implicated the function of G protein-coupled receptor (GPR)-30
      with nongenomic effects of estrogen, suggesting that GPR30 might be a G-protein
      coupled estrogen receptor. However, the findings are controversial and the
      expression pattern of GPR30 on a cell type level as well as its function in vivo
      remains unclear. Therefore, the objective of this study was to identify cell
      types that express Gpr30 in vivo by analyzing a mutant mouse model that harbors a
      lacZ reporter (Gpr30-lacZ) in the Gpr30 locus leading to a partial deletion of
      the Gpr30 coding sequence. Using this strategy, we identified the following cell
      types expressing Gpr30: 1) an endothelial cell subpopulation in small arterial
      vessels of multiple tissues, 2) smooth muscle cells and pericytes in the brain,
      3) gastric chief cells in the stomach, 4) neuronal subpopulations in the cortex
      as well as the polymorph layer of the dentate gyrus, 5) cell populations in the
      intermediate and anterior lobe of the pituitary gland, and 6) in the medulla of
      the adrenal gland. In further experiments, we aimed to decipher the function of
      Gpr30 by analyzing the phenotype of Gpr30-lacZ mice. The body weight as well as
      fat mass was unchanged in Gpr30-lacZ mice, even if fed with a high-fat diet. Flow
      cytometric analysis revealed lower frequencies of T cells in both sexes of Gpr30
      lacZ mice. Within the T-cell cluster, the amount of CD62L-expressing cells was
      clearly reduced, suggesting an impaired production of T cells in the thymus of
      Gpr30-lacZ mice.

PMID- 19095740
TI  - Postnatal stress in birds: a novel model of glucocorticoid programming of the
      hypothalamic-pituitary-adrenal axis.
AB  - There is growing international interest in how environmental conditions
      experienced during development can shape adult phenotypes and the extent to which
      such induced changes are adaptive. One physiological system that links an
      individual to changes in environmental circumstances during development is the
      hypothalamic-pituitary-adrenal axis. Mammalian studies have linked early
      postnatal stress to later changes in the hypothalamic-pituitary-adrenal axis;
      however, the physiological link [lactational corticosterone (CORT) transfer]
      between mother and offspring during postnatal development constrains the ability
      to determine the direct effects of such stressors on subsequent physiology and
      behavior. Here we present a novel model using an avian species, the zebra finch
      (Taeniopygia guttata), in which maternal hormonal transfer during postnatal
      development is likely to be absent. Postnatal exposure of chicks to the stress
      hormone CORT was manipulated for a 16-d period up until nutritional independence
      (28 d), and the long-term effects on the physiological response to stress
      determined. CORT doses were scaled to mimic the physiological response of
      juvenile birds to a capture-handling-restraint protocol. CORT-fed birds showed
      exaggerated and prolonged responses to acute stress at 60 d of age. Our results
      clearly demonstrate that postnatal stress has significant long-term effects on
      the physiological stress response in birds and provides a potential mechanism
      underlying long-term behavioural responses to developmental conditions. This
      study represents the first direct evidence for postnatal glucocorticoid
      programming of the stress response using this novel model for postnatal stress.
      This model therefore provides an important tool with which to investigate the
      role of glucocorticoids in shaping adult phenotypes.

PMID- 19095742
TI  - Prolactin treatment improves engraftment and function of transplanted pancreatic
      islets.
AB  - Transplantation of pancreatic islets is clinically used to treat type 1 diabetes
      but requires multiple donors. Previous experimental studies demonstrated that
      transplanted islets have a low blood vessel density, which leads to a hypoxic
      microenvironment. The present study tested the hypothesis that experimental
      prolactin pretreatment, a substance that seems to stimulate angiogenesis in
      endogenous islets, would increase graft blood vessel density, thereby improving
      transplantation outcome. Pancreatic islets from C57BL/6 mice were incubated with
      prolactin (500 ng/ml) or vehicle during the last 24 h of culture before syngeneic
      transplantation beneath the renal capsule, or recipients were injected with
      prolactin or vehicle for the first 7 d after transplantation. One month after
      transplantation, graft vascular density, blood flow, oxygen tension, endocrine
      volume, and function were evaluated. Also, human islets were incubated with
      prolactin or vehicle before experimental transplantation and investigated for
      vascular engraftment. Vascular engraftment of syngeneically transplanted mouse
      islets was improved by both in vivo and in vitro prolactin pretreatment.
      Moreover, prolactin pretreatment in vitro of islets used for transplantation
      improved recovery from diabetes in a minimal islet mass model. Interestingly,
      also human islets subjected to prolactin treatment before experimental
      transplantation demonstrated improved revascularization, blood perfusion, and
      oxygen tension when evaluated 1 month after transplantation. We conclude that
      prolactin may improve engraftment of transplanted pancreatic islets. The protocol
      with pretreatment of islets ex vivo could minimize the risk of side effects when
      used in the clinical setting.

PMID- 19095741
TI  - A protective role for type 3 deiodinase, a thyroid hormone-inactivating enzyme,
      in cochlear development and auditory function.
AB  - Thyroid hormone is necessary for cochlear development and auditory function, but
      the factors that control these processes are poorly understood. Previous evidence
      indicated that in mice, the serum supply of thyroid hormone is augmented within
      the cochlea itself by type 2 deiodinase, which amplifies the level of T(3), the
      active form of thyroid hormone, before the onset of hearing. We now report that
      type 3 deiodinase, a thyroid hormone-inactivating enzyme encoded by Dio3, is
      expressed in the immature cochlea before type 2 deiodinase. Dio3-/- mice display
      auditory deficits and accelerated cochlear differentiation, contrasting with the
      retardation caused by deletion of type 2 deiodinase. The Dio3 mRNA expression
      pattern in the greater epithelial ridge, stria vascularis, and spiral ganglion
      partly overlaps with that of thyroid hormone receptor beta (TRbeta), the T(3)
      receptor that is primarily responsible for auditory development. The proposal
      that type 3 deiodinase prevents premature stimulation of TRbeta was supported by
      deleting TRbeta, which converted the Dio3-/- cochlear phenotype from one of
      accelerated to one of delayed differentiation. The results indicate a protective
      role for type 3 deiodinase in hearing. The auditory system illustrates the
      considerable extent to which tissues can autoregulate their developmental
      response to thyroid hormone through both type 2 and 3 deiodinases.

PMID- 19095743
TI  - Disruption of tubulobulbar complex by high intratesticular estrogens leading to
      failed spermiation.
AB  - Spermiation is the final phase of spermatogenesis leading to release of mature
      spermatids into the lumen of the seminiferous tubules. Morphologically, it
      involves a series of events, namely removal of excess spermatid cytoplasm,
      removal of ectoplasmic specialization, formation of tubulobulbar complex, and
      final disengagement of the spermatid from the Sertoli cell. Previous studies in
      our laboratory have shown that administration of 17beta-estradiol at a dose of
      100 microg/kg body weight for 10 d resulted in failure of spermiation. This was
      accompanied by a suppression of FSH and intratesticular testosterone with a
      concomitant rise in intratesticular 17beta-estradiol. The present study was
      undertaken to determine the cause of failure and subsequently the molecular
      events in spermiation. Electron microscopic and confocal studies revealed an
      absence of tubulobulbar complex in step 19 spermatids after estradiol treatment,
      highlighting the significance of these structures in spermiation. It was further
      observed that treatment affected the Sertoli cell cytoskeleton and Arp2/3 complex
      that is critical for de novo polymerization of actin during tubulobulbar complex
      formation. In conclusion, the present study reports the role of 17beta-estradiol
      in inhibiting the formation of tubulobulbar complex, which could be one of the
      mechanism by which environmental estrogens influence male fertility.

PMID- 19095744
TI  - Maturation of adult beta-cells revealed using a Pdx1/insulin dual-reporter
      lentivirus.
AB  - The enigmatic process of beta-cell maturation has significant implications for
      diabetes pathogenesis, and potential diabetes therapies. This study examined the
      dynamics and heterogeneity of insulin and pancreatic duodenal homeobox (Pdx)-1
      gene expression in adult beta-cells. Insulin and Pdx1 expression were monitored
      in human and mouse islet cells and MIN6 cells using a Pdx1-monomeric red
      fluorescent protein/insulin-enhanced green fluorescent protein dual-reporter
      lentivirus. The majority of fluorescent cells were highly positive for both Pdx1
      and insulin. Cells expressing Pdx1 but little or no insulin (Pdx1(+)/Ins(low))
      comprised 15-25% of the total population. Time-lapse imaging demonstrated that
      Pdx1(+)/Ins(low) primary beta-cells and MIN6 cells could convert to
      Pdx1(+)/Ins(+) cells without cell division. Genes involved in the mature beta
      cell phenotype (Glut2, MafA) were expressed at higher levels in Pdx1(+)/Ins(+)
      cells relative to Pdx1(+)/Ins(low) cells. Conversely, genes implicated in early
      beta-cell development (MafB, Nkx2.2) were enriched in Pdx1(+)/Ins(low) cells.
      Sorted Pdx1(+)/Ins(low) MIN6 cells had a higher replication rate and secreted
      less insulin relative to double-positive cells. Long-term phenotype tracking of
      Pdx1(+)/Ins(low) cells showed two groups, one that matured into Pdx1(+)/Ins(+)
      cells and one that remained immature. These results demonstrate that adult beta
      cells pass through distinct maturation states, which is consistent with
      previously observed heterogeneity in insulin and Pdx1 expression in adult beta
      cells. At a given time, a proportion of adult beta-cells share similar
      characteristics to functionally immature embryonic beta-cell progenitors. The
      maturation of adult beta-cells recapitulates development in that Pdx1 expression
      precedes the robust expression of insulin and other mature beta-cell genes. These
      results have implications for harnessing the maturation process for therapeutic
      purposes.

PMID- 19095745
TI  - Aldosterone inhibits insulin-induced glucose uptake by degradation of insulin
      receptor substrate (IRS) 1 and IRS2 via a reactive oxygen species-mediated
      pathway in 3T3-L1 adipocytes.
AB  - Serum aldosterone level is clinically known to correlate with body weight and
      insulin resistance. Because the underlying molecular mechanism is largely
      unknown, we examined the effect of aldosterone on insulin-induced metabolic
      signaling leading to glucose uptake in 3T3-L1 adipocytes. Aldosterone reduced the
      amounts of insulin receptor substrate (IRS) 1 and IRS2 in a time- and dose
      dependent manner. As a result, insulin-induced phosphorylation of Akt-1 and -2,
      and subsequent uptake of 2-deoxyglucose were decreased. Degradation of IRSs was
      effectively prevented by a glucocorticoid receptor antagonist and antioxidant N
      acetylcysteine, but not by a mineralocorticoid receptor antagonist. Because
      aldosterone induced phosphorylation of IRS1 at Ser(307), responsible kinases were
      investigated, and we revealed that rapamycin and BMS345541, but neither SP600125
      nor calphostin C, conferred for degradation of IRSs. Although lactacystin
      prevented the degradation of IRSs, glucose uptake was not preserved. Importantly,
      sucrose-gradient-sediment intracellular fraction analysis revealed that
      lactacystin did not effectively restore the reduction of IRS1 in the low-density
      microsome fraction, important for the transduction of insulin's metabolic
      signaling. These results indicate that aldosterone deteriorates metabolic action
      of insulin by facilitating the degradation of IRS1 and IRS2 via glucocorticoid
      receptor-mediated production of reactive oxygen species, and activation of
      IkappaB Kinase beta and target of rapamycin complex 1. Thus, aldosterone appears
      to be a novel key factor in the development of insulin resistance in visceral
      obesity.

PMID- 19095746
TI  - Unique roles of p160 coactivators for regulation of breast cancer cell
      proliferation and estrogen receptor-alpha transcriptional activity.
AB  - Each of the three members of the p160 steroid receptor coactivator (SRC) family
      of coactivators (SRC-1, SRC-2 and SRC-3) stimulates estrogen receptor (ER)-alpha
      function in trans-activation assays. Consequently, we sought to elucidate their
      contributions to the ER-regulated processes of cell proliferation, apoptosis, and
      the expression of ERalpha target genes in MCF-7 breast cancer cells. The small
      interfering RNA depletion of SRC-2 or SRC-3 but not SRC-1 inhibited growth of MCF
      7 cells, and this was reflected in decreased cell cycle progression and increased
      apoptosis in SRC-2- or SRC-3-depleted cells as well as a reduction in ERalpha
      transcriptional activity measured on a synthetic reporter gene. However, only SRC
      3 depletion blocked estradiol stimulated cell proliferation. Depletion of SRC-1
      did not affect these events, and together this reveals functional differences
      between each of the three SRC family coactivators. Regulation of the endogenous
      ERalpha target gene, c-myc was not affected by depletion of any of the p160
      coactivators although depletion of each of them decreased pS2 mRNA expression in
      estradiol-treated MCF-7 cells. Moreover, progesterone receptor and cyclin D1 gene
      expression were decreased in SRC-3 small interfering RNA-treated cells.
      Expression of mRNA and protein levels for the antiapoptotic gene, Bcl-2 was
      dependent on SRC-3 expression, whereas Bcl-2 protein but not mRNA expression also
      was sensitive to SRC-1 depletion. Together these data indicate that the closely
      related p160 coactivators are not functionally redundant in breast cancer cells
      because they play gene-specific roles in regulating mRNA and protein expression,
      and they therefore are likely to make unique contributions to breast
      tumorigenesis.

PMID- 19095748
TI  - Fatigue in working muscles.

PMID- 19095747
TI  - JP-8 induces immune suppression via a reactive oxygen species NF-kappabeta
      dependent mechanism.
AB  - Applying jet fuel (JP-8) to the skin of mice induces immune suppression. JP-8
      treated keratinocytes secrete prostaglandin E(2), which is essential for
      activating immune suppressive pathways. The molecular pathway leading to the
      upregulation of the enzyme that controls prostaglandin synthesis, cyclooxygenase
      (COX)-2, is unclear. Because JP-8 activates oxidative stress and because reactive
      oxygen species (ROS) turn on nuclear factor kappa B (NF-kappabeta), which
      regulates the activity of COX-2, we asked if JP-8-induced ROS and NF-kappabeta
      contributes to COX-2 upregulation and immune suppression in vivo. JP-8 induced
      the production of ROS in keratinocytes as measured with the ROS indicator dye,
      aminophenyl fluorescein. Fluorescence was diminished in JP-8-treated
      keratinocytes overexpressing catalase or superoxide dismutase (SOD) genes. JP-8
      induced COX-2 expression was also reduced to background in the catalase and SOD
      transfected cells, or in cultures treated with N-acetylcysteine (NAC). When NAC
      was injected into JP-8-treated mice, dermal COX-2 expression, and JP-8-induced
      immune suppression was inhibited. Because ROS activates NF-kappabeta, we asked if
      this transcriptional activator played a role in the enhanced COX-2 expression and
      JP-8-induced immune suppression. When JP-8-treated mice, or JP-8-treated
      keratinocytes were treated with a selective NF-kappabeta inhibitor, parthenolide,
      COX-2 expression, and immune suppression were abrogated. Similarly, when JP-8
      treated keratinocytes were treated with small interfering RNA specific for the
      p65 subunit of NF-kappabeta, COX-2 upregulation was blocked. These data indicate
      that ROS and NF-kappabeta are activated by JP-8, and these pathways are involved
      in COX-2 expression and the induction of immune suppression by jet fuel.

PMID- 19095749
TI  - Energetics and mammary carcinogenesis: effects of moderate-intensity running and
      energy intake on cellular processes and molecular mechanisms in rats.
AB  - The objective of this experiment was to determine the effects on mammary
      carcinogenesis of similar limitations in energy availability either by energy
      expenditure due to moderate-intensity running (physical activity, PA) or by
      regulating dietary energy (RE) intake relative to a sedentary control (SC) group
      that ate ad libitum. A total of 90 female Sprague-Dawley rats were injected with
      1-methyl-1-nitrosourea (50 mg/kg) and 7 days thereafter were randomized to either
      SC, a PA group given free access to a motorized running wheel, or a RE group
      whose food intake limited growth to the rate observed in PA. Compared with SC,
      mammary carcinogenesis was inhibited by RE or PA. Cancer incidence, 92.6%, 77.8%,
      and 66.7% (P = 0.06), and cancer multiplicity, 3.44, 2.11, and 1.62 cancers/rat
      (P = 0.006), in SC, RE, and PA, respectively, were reduced to a similar extent by
      RE and PA. Histological and Western blot analyses of mammary carcinomas provided
      evidence that RE and PA induced apoptosis via the mitochondrial pathway, that
      cell cycle progression was suppressed at the G(1)/S transition, and that
      intratumoral blood vessel density was reduced, although it remains to be
      determined whether PA and RE exert these effects via the same mechanisms.

PMID- 19095750
TI  - Stress responses and baroreflex function in coronary disease.
AB  - Exaggerated pressor responses to mental stress in patients with coronary artery
      disease (CAD) are associated with increased risk for subsequent cardiovascular
      events. The integrated baroreflex gain and its mechanical and neural component
      were estimated and then related to the blood pressure and heart rate responses to
      simulated real-life stressors: mental arithmetic and public speaking. Eighteen
      healthy individuals (aged 61 +/- 8 yr) and 29 individuals with documented CAD but
      no other comorbidities (aged 59 +/- 8 yr) were studied. Heart rate and blood
      pressures were continuously assessed before, during preparation for, and during
      performance of a math task and a speech task. The assessment of beat-to-beat
      carotid diameters during baroreflex engagement was used to estimate the
      integrated baroreflex gain and its mechanical and neural component. The CAD
      subjects demonstrated significantly greater increases in heart rate and blood
      pressures for the performance of the speech task. However, there were no group
      differences in integrated cardiovagal baroreflex gain or either mechanical or
      neural baroreflex component. These findings indicate that the augmented pressor
      responses in CAD do not result from a generalized arterial baroreflex deficit.

PMID- 19095751
TI  - Anthropometry, CT, and DXA as predictors of GH deficiency in premenopausal women:
      ROC curve analysis.
AB  - Visceral adiposity is a strong determinant of growth hormone (GH) secretion, and
      states of GH deficiency are associated with increased visceral adiposity and
      decreased lean body mass. The purpose of our study was to determine the
      sensitivity and specificity of different methods of assessing body composition
      [anthropometry, dual-energy X-ray absorptiometry (DXA), and computed tomography
      (CT)] to predict GH deficiency in premenopausal women and threshold values for
      each technique to predict GH deficiency, using receiver operator characteristic
      (ROC) curve analysis. We studied a group of 45 healthy lean, overweight, and
      obese premenopausal women who underwent anthropometric measurements (body mass
      index, waist and hip circumferences, skin fold thickness), DXA, CT, and a GH
      releasing hormone-arginine stimulation test. ROC curve analysis was used to
      determine cutoff values for each method to identify GH deficiency. Visceral
      adiposity measured by CT showed the highest sensitivity and specificity for
      identifying subjects with GH deficiency with a cutoff of >9,962 mm(2) [area under
      the curve (AUC), 0.95; sensitivity, 100%; specificity, 77.8%; P = 0.0001].
      Largest waist circumference showed high sensitivity and specificity with a cutoff
      of >101.7 cm (AUC, 0.89; sensitivity, 88.9%; specificity, 75%; P = 0.0001). When
      the ROC curves of visceral fat measured by CT and largest waist circumference
      were compared, the difference between the two methods was not statistically
      significant (P = 0.36). Our study showed that the largest waist circumference
      predicts the presence of GH deficiency in healthy premenopausal women with high
      sensitivity and specificity and nearly as well as CT measurement of visceral
      adiposity. It can be used to identify women in whom GH deficiency is likely and
      therefore in whom formal GH stimulation testing might be indicated.

PMID- 19095753
TI  - Control of breathing and volitional respiratory rhythm in humans.
AB  - When breathing frequency (f) is imperceptibly increased during a volitionally
      paced respiratory rhythm imposed by an auditory signal, tidal volume (Vt)
      decreases such that minute ventilation (Ve) rises according to f-induced dead
      space ventilation changes (18). As a result, significant change in alveolar
      ventilation and Pco(2) are prevented as f varies. The present study was performed
      to determine what regulatory properties are retained by the respiratory control
      system, wherein the spontaneous automatic rhythmic activity is replaced by a
      volitionally paced rhythm. Six volunteers were asked to trigger each breath cycle
      on hearing a brief auditory signal. The time interval between subsequent auditory
      signals was imperceptibly changed for 10-15 min, during 1) air breathing
      (condition 1), 2) the addition of a 300 ml of instrumental dead space (condition
      2), 3) an increase in the inspired level of CO(2) (condition 3), and 4) light
      exercise (condition 4). We found that as f was slowly increased the elaborated Vt
      decreased in accordance to the background level of CO(2) and metabolic rate.
      Indeed, for any given breath duration, Vt was shifted upward in condition 2 vs.
      1, whereas the slope of Vt changes according to the volitionally rhythm was much
      steeper in conditions 3 and 4 vs. 1. The resulting changes in Ve offset any f
      induced changes in dead-space ventilation in all conditions. We conclude that
      there is an inherent, fundamental mechanism that elaborates Vt based on f when
      imposed by the premotor cortex in humans. The chemoreflex and exercise drive to
      breath interacts with this cortically mediated rhythm maintaining alveolar rather
      than Ve constant as f changes. The implications of our findings are discussed in
      the context of our current understanding of the central generation of breathing
      rhythm.

PMID- 19095754
TI  - Effects of galvanic mastoid stimulation in seated human subjects.
AB  - The vestibular responses evoked by transmastoid galvanic stimulation (GS) in the
      rectified soleus electromyogram (EMG) in freely standing human subjects disappear
      when seated. However, a GS-induced facilitation of the soleus monosynaptic (H and
      tendon jerk) reflex has been described in few experiments in subjects lying prone
      or seated. This study addresses the issue of whether this reflex facilitation
      while seated is of vestibulospinal origin. GS-induced responses in the soleus
      (modulation of the rectified ongoing EMG and of the monosynaptic reflexes) were
      compared in the same normal subjects while freely standing and sitting with back
      and head support. The polarity-dependent biphasic responses in the free-standing
      position were replaced by a non-polarity-dependent twofold facilitation while
      seated. The effects of GS were hardly detectable in the rectified ongoing
      voluntary EMG activity, weak for the H reflex, but large and constant for the
      tendon jerk. They were subject to habituation. Anesthesia of the skin beneath the
      GS electrodes markedly reduced the reflex facilitation, while a similar, although
      weaker, facilitation of the tendon jerk was observed when GS was replaced with
      purely cutaneous stimulation, a tap to the tendon of the sternomastoid muscle, or
      an auditory click. The stimulation polarity independence of the GS-induced reflex
      facilitation argues strongly against a vestibular response. However, the
      vestibular afferent volley, insufficient to produce a vestibular reflex response
      while seated, could summate with the GS-induced tactile or proprioceptive volley
      to produce a startle-like response responsible for the reflex facilitation.

PMID- 19095752
TI  - Normal breathing pattern and arterial blood gases in awake and sleeping goats
      after near total destruction of the presumed pre-Botzinger complex and the
      surrounding region.
AB  - Abrupt neurotoxic destruction of >70% of the pre-Botzinger complex (preBotzC) in
      awake goats results in respiratory and cardiac failure (Wenninger JM, Pan LG,
      Klum L, Leekley T, Bastastic J, Hodges MR, Feroah TR, Davis S, Forster HV. J Appl
      Physiol 97: 1629-1636, 2004). However, in reduced preparations, rhythmic
      respiratory activity has been found in other areas of the brain stem (Huang Q,
      St. John WM. J Appl Physiol 64: 1405-1411, 1988; Janczewski WA, Feldman JL. J
      Physiol 570: 407-420, 2006; Lieske SP, Thoby-Brisson M, Telgkamo P, Ramierz JM.
      Nature Neurosci 3: 600-607, 2000; St. John WM, Bledsoe TA. J Appl Physiol 59: 684
      690, 1985); thus we hypothesized that, when the preBotzC is destroyed
      incrementally over weeks, time-dependent plasticity within the respiratory
      network will result in a respiratory rhythm capable of maintaining normal blood
      gases. Microtubules were bilaterally implanted into the presumed preBotzC of
      seven goats. After recovery from surgery, studies were completed to establish
      baseline values for respiratory parameters. At weekly intervals, increasing
      volumes (in order 0.5, 1, 5, and 10 microl) of ibotenic acid (IA; 50 mM) were
      then injected into the preBotzC. All IA injections resulted in an acute tachypnea
      and dysrhythmia featuring augmented breaths, apneas, and increased breath-to
      breath variation in breathing. In studies at night, apneas were nearly all
      central and occurred in the awake state. Breath-to-breath variation in breathing
      was greater (P < 0.05) during wakefulness than during non-rapid eye movement
      sleep. However, one week after the final IA injection, the breathing pattern,
      breath-to-breath variation, and arterial blood gases and pH were unchanged from
      baseline, but there was a 20% decrease in respiratory frequency (f) and CO(2)
      sensitivity (P < 0.05), as well as a 40% decrease in the ventilatory response to
      hypoxia (P < 0.001). In subsequent histological analysis of the presumed preBotzC
      region of lesioned goats, it was determined that there was a 90 and 92% reduction
      from control goats in total and neurokinin-1 receptor neurons, respectively.
      Therefore, it was concluded that 1) the dysrhythmic effects on breathing are
      state dependent; and 2) after incremental, near total destruction of the presumed
      preBotzC region, time-dependent plasticity within the respiratory network
      provides a rhythm capable of sustaining normal arterial blood gases.

PMID- 19095755
TI  - Inferring selection on amino acid preference in protein domains.
AB  - Models that explicitly account for the effect of selection on new mutations have
      been proposed to account for "codon bias" or the excess of "preferred" codons
      that results from selection for translational efficiency and/or accuracy. In
      principle, such models can be applied to any mutation that results in a preferred
      allele, but in most cases, the fitness effect of a specific mutation cannot be
      predicted. Here we show that it is possible to assign preferred and unpreferred
      states to amino acid changing mutations that occur in protein domains. We propose
      that mutations that lead to more common amino acids (at a given position in a
      domain) can be considered "preferred alleles" just as are synonymous mutations
      leading to codons for more abundant tRNAs. We use genome-scale polymorphism data
      to show that alleles for preferred amino acids in protein domains occur at higher
      frequencies in the population, as has been shown for preferred codons. We show
      that this effect is quantitative, such that there is a correlation between the
      shift in frequency of preferred alleles and the predicted fitness effect. As
      expected, we also observe a reduction in the numbers of polymorphisms and
      substitutions at more important positions in domains, consistent with stronger
      selection at those positions. We examine the derived allele frequency
      distribution and polymorphism to divergence ratios of preferred and unpreferred
      differences and find evidence for both negative and positive selections acting to
      maintain protein domains in the human population. Finally, we analyze a model for
      selection on amino acid preferences in protein domains and find that it is
      consistent with the quantitative effects that we observe.

PMID- 19095756
TI  - A little bit pregnant: modeling how the accurate detection of pregnancy can
      improve HIV prevention trials.
AB  - The prevalence of unplanned pregnancies contributes to the methodological
      challenges of human immunodeficiency virus (HIV) prevention trials. In this
      paper, the authors discuss the incidence of pregnancy, including chemical
      pregnancy, and how the different methods of pregnancy diagnosis could affect the
      statistical power and calculated outcomes of HIV prevention trials. Study sample
      size inflation factors are estimated to aid in the design of clinical trials.The
      authors used published data of women attempting pregnancy as well as data from
      HPTN 055 (www.HPTN.org/research_studies/hptn055.asp) to estimate the percentage
      of early study discontinuation that would be associated with 3 diagnostic methods
      for pregnancy in a hypothetical clinical trial. They classified chemical
      pregnancies as false-positive pregnancy tests and showed the sample size
      adjustment that would be necessary in clinical trial design because of the early
      discontinuations associated with pregnancy. There is a greater than 3-fold
      difference in the number of falsely positive pregnancy tests that will be
      detected, depending upon the diagnostic method used. The number of incident
      pregnancies may render HIV prevention trial sample sizes inadequate by as much as
      50%. Pregnancy prevention and precise pregnancy diagnosis are critical to the
      statistical power and integrity of HIV prevention trials.

PMID- 19095757
TI  - Dietary glycemic index, glycemic load, and risk of cancer: a prospective cohort
      study.
AB  - Previous studies have provided limited evidence for a harmful effect of high
      glycemic index and dietary glycemic load on cancer. The authors analyzed
      associations among glycemic index, glycemic load, and risk of cancer in women and
      men in the National Institutes of Health-AARP Diet and Health Study. Published
      glycemic index values were assigned to 225 foods/food groups. Glycemic load was
      calculated by multiplying the glycemic index, carbohydrate content, and intake
      frequency of individual foods reported on a food frequency questionnaire. From
      1995 through 2003, the authors identified 15,215 and 33,203 cancer cases in women
      and men, respectively. Cox proportional hazards models were used to estimate
      multivariate relative risks and 95% confidence intervals. For women and men,
      respectively, the relative risks for total cancer for high versus low glycemic
      index were 1.03 (P(trend)=0.217) and 1.04 (P(trend)=0.012) and, for glycemic
      load, were 0.90 (P(trend)=0.024) and 0.93 (P(trend)=0.01). Associations with
      total cancer held only among the overweight for glycemic index and among those of
      healthy weight for glycemic load. These findings suggest that glycemic index and
      glycemic load are not strong predictors of cancer incidence. The direction and
      small magnitude of associations might be explained by the manner in which high
      glycemic index and glycemic load track with overall diet and lifestyle patterns.

PMID- 19095758
TI  - Periods of recovery in deficit syndrome schizophrenia: a 20-year multi-follow-up
      longitudinal study.
AB  - Periods of recovery were examined in patients with and without deficit syndrome
      schizophrenia. Fifty-six patients with schizophrenia were studied, 39 of whom
      were divided into deficit and nondeficit syndrome schizophrenia subtypes using a
      proxy method. We also studied 39 nonpsychotic depressive comparison patients.
      Patients were evaluated as part of the Chicago Follow-up Study, which
      prospectively examined patients at regular intervals over a 20-year period. Using
      standardized instruments, patients were evaluated for the deficit syndrome,
      global recovery, rehospitalization, social dysfunction, occupational disability,
      and symptom presentation. Recovery was examined at 6 time points measured at 2-,
      4.5-, 7.5-, 10-, 15-, and 20-year postindex hospitalization. Cumulatively, over
      the 20-year period, 13% of patients classified as meeting criteria for the
      deficit syndrome showed 1 or more 1-year periods of global recovery, in
      comparison to 63% of nondeficit schizophrenia patients and 77% of depressed
      patient controls. Results indicate that the deficit syndrome represents a
      persistently impaired subsample of schizophrenia patients, with continuous
      social, occupational, and symptom impairment. In contrast, nondeficit syndrome
      schizophrenia patients showed at least some periods of remission or recovery,
      with the likelihood of these periods increasing as they became older. Findings
      provide further support for the validity of the deficit syndrome concept and
      suggest that deficit status is characterized by a more persistently impaired
      course of illness and particularly poor long-term prognosis.

PMID- 19095759
TI  - Functional ENTPD1 polymorphisms in African Americans with diabetes and end-stage
      renal disease.
AB  - OBJECTIVE: The vascular ectonucleotidase ENTPD1 protects against renal injury and
      modulates glucose homeostasis in mouse models. We sought to determine whether
      human variation in ENTPD1 influences predisposition to diabetes or diabetic
      nephropathy. RESEARCH DESIGN AND METHODS: We analyzed ENTPD1 single nucleotide
      polymorphisms (SNPs) in 363 African American control subjects, 380 subjects with
      type 2 diabetes and end-stage renal disease (DM-ESRD), and 326 subjects with ESRD
      unrelated to diabetes (non-DM-ESRD). Using human cell lines, we correlated
      disease-associated ENTPD1 haplotypes with ENTPD1 gene expression. Finally, we
      studied consequences of ENTPD1 deletion in a mouse model of type 2 diabetes
      (db/db). RESULTS: A common ENTPD1 two-SNP haplotype was associated with increased
      risk for DM-ESRD (P = 0.0027), and an uncommon four-SNP haplotype was associated
      with protection against DM-ESRD (P = 0.004). These haplotypes correlated with
      ENTPD1 gene expression levels in human cell lines in vitro. Subjects with high
      ENTPD1-expressing haplotypes were enriched in the DM-ESRD group. By crossing
      ENTPD1-null mice with db mice, we show that ENTPD1 deletion has prominent effects
      on metabolic syndrome traits. Specifically, deletion of ENTPD1 lowered glucose
      levels in control (db/-) mice with one functional leptin receptor and
      dramatically lowered weights in db/db mice with no functional leptin receptors.
      Similar effects were seen in aged ENTPD1-null mice with normal leptin receptors.
      CONCLUSIONS: ENTPD1 polymorphisms appear to influence susceptibility to type 2
      diabetes and/or diabetic nephropathy in African Americans. Studies in human cell
      lines and in vivo mouse data support a potential role for ENTPD1 genetic
      variation in susceptibility to type 2 diabetes.

PMID- 19095760
TI  - Relationship between cerebrospinal fluid visfatin (PBEF/Nampt) levels and
      adiposity in humans.
AB  - OBJECTIVE: Observations of elevated circulating concentrations of visfatin
      (PBEF/Nampt) in obesity and diabetes suggest that this recently described
      adipokine is involved in the regulation of body weight and metabolism. We
      examined in humans whether visfatin is found in cerebrospinal fluid (CSF) and, if
      so, how CSF visfatin concentrations relate to adiposity and metabolic parameters.
      RESEARCH DESIGN AND METHODS: We measured visfatin concentrations in the plasma
      and CSF of 38 subjects (18 men and 20 women; age 19-80 years) with a wide range
      of body weight (BMI 16.24-38.10 kg/m2). In addition, anthropometric parameters
      and endocrine markers were assessed. Bivariate correlation coefficients were
      determined and stepwise multiple regression analyses were performed to detect
      associations of CSF and plasma visfatin levels with relevant parameters. RESULTS:
      Plasma visfatin levels increased with rising BMI (P < 0.0001) and body fat mass
      (P < 0.0001). In contrast, CSF visfatin levels decreased with increasing plasma
      visfatin concentrations (P < 0.03), BMI (P < 0.001), body fat mass (P < 0.0001),
      and insulin resistance (P < 0.05). Body fat was the only factor independently
      associated with CSF visfatin, explaining 58% of the variation of CSF visfatin
      levels (P < 0.0001). Neither plasma (P > 0.13) nor CSF (P > 0.61) visfatin
      concentrations differed between men and women. CONCLUSIONS: Our data indicate
      that visfatin concentrations in human CSF decrease with rising body fat,
      supporting the assumption that visfatin transport across the blood-brain barrier
      is impaired in obesity and that central nervous visfatin insufficiency or
      resistance are linked to pathogenetic mechanisms of obesity.

PMID- 19095761
TI  - Protein kinase A regulatory subunits in human adipose tissue: decreased R2B
      expression and activity in adipocytes from obese subjects.
AB  - OBJECTIVE: In human adipocytes, the cAMP-dependent pathway mediates signals
      originating from beta-adrenergic activation, thus playing a key role in the
      regulation of important metabolic processes, i.e., lipolysis and thermogenesis.
      Cyclic AMP effects are mainly mediated by protein kinase A (PKA), whose R2B
      regulatory isoform is the most expressed in mouse adipose tissue, where it
      protects against diet-induced obesity and fatty liver development. The aim of the
      study was to investigate possible differences in R2B expression, PKA activity,
      and lipolysis in adipose tissues from obese and nonobese subjects. RESEARCH
      DESIGN AND METHODS: The expression of the different PKA regulatory subunits was
      evaluated by immunohistochemistry, Western blot, and real-time PCR in
      subcutaneous and visceral adipose tissue samples from 20 nonobese and 67 obese
      patients. PKA activity and glycerol release were evaluated in total protein
      extract and adipocytes isolated from fresh tissue samples, respectively. RESULTS:
      Expression techniques showed that R2B was the most abundant regulatory protein,
      both at mRNA and protein level. Interestingly, R2B mRNA levels were significantly
      lower in both subcutaneous and visceral adipose tissues from obese than nonobese
      patients and negatively correlated with BMI, waist circumference, insulin levels,
      and homeostasis model assessment of insulin resistance. Moreover, both basal and
      stimulated PKA activity and glycerol release were significantly lower in visceral
      adipose tissue from obese patients then nonobese subjects. CONCLUSIONS: Our
      results first indicate that, in human adipose tissue, there are important BMI
      related differences in R2B expression and PKA activation, which might be included
      among the multiple determinants involved in the different lipolytic response to
      beta-adrenergic activation in obesity.

PMID- 19095762
TI  - Beta- and alpha-cell dysfunction in subjects developing impaired glucose
      tolerance: outcome of a 12-year prospective study in postmenopausal Caucasian
      women.
AB  - OBJECTIVE: This study assessed insulin and glucagon secretion in relation to
      insulin sensitivity in Caucasian women who develop impaired glucose tolerance
      (IGT) versus those who maintain normal glucose tolerance (NGT) over a 12-year
      period. RESEARCH DESIGN AND METHODS: At baseline and after 3, 8, and 12 years,
      glucose tolerance (75-g oral glucose tolerance test), insulin sensitivity
      (euglycemic-hyperinsulinemic clamp), and insulin and glucagon secretion (2- to 5
      min responses to 5 g arginine i.v. at fasting, 14 and >25 mmol/l glucose) were
      determined in 53 healthy Caucasian women (aged 58 years at baseline) who all had
      NGT at baseline. RESULTS: During the 12-year period, 26 subjects developed IGT,
      whereas the remaining 27 subjects maintained NGT throughout the 12-year period.
      Subjects developing IGT had lower insulin sensitivity than those maintaining NGT
      in the tests preceding diagnosis of IGT (P < or = 0.05). When judged in relation
      to insulin sensitivity, beta-cell glucose sensitivity and maximal insulin
      secretion were lower in those who later developed IGT than in those maintaining
      NGT at all tests (P < or = 0.05). Furthermore, subjects who developed IGT had
      defective suppression of glucagon secretion by glucose in the test preceding
      diagnosis of IGT when they still had NGT (P < or = 0.05). CONCLUSIONS: Beta- and
      alpha-cell dysfunction are evident several years before diagnosis of IGT, and
      islet dysfunction is manifested as impaired glucose sensitivity of the beta- and
      alpha-cells and reduced maximal insulin secretion.

PMID- 19095763
TI  - Role of serotonin in intestinal inflammation: knockout of serotonin reuptake
      transporter exacerbates 2,4,6-trinitrobenzene sulfonic acid colitis in mice.
AB  - Serotonin (5-HT) regulates peristaltic and secretory reflexes in the gut. The
      serotonin reuptake transporter (SERT; SLC6A4), which inactivates 5-HT, is
      expressed in the intestinal mucosa and the enteric nervous system. Stool water
      content is increased and colonic motility is irregular in mice with a targeted
      deletion of SERT. We tested the hypotheses that 5-HT plays a role in regulating
      intestinal inflammation and that the potentiation of serotonergic signaling that
      results from SERT deletion is proinflammatory. Rectal installation of 2,4,6
      trinitrobenzene sulfonic acid (TNBS) was used to induce an immune-mediated
      colitis, which was compared in SERT knockout mice and littermate controls.
      Intestinal myeloperoxidase and histamine levels were significantly increased,
      whereas the survival rate and state of health were significantly decreased in
      TNBS-treated mice that lacked SERT. Deletion of SERT thus increases the severity
      of TNBS colitis. These data suggest that 5-HT and its SERT-mediated termination
      play roles in intestinal immune/inflammatory responses in mice.

PMID- 19095764
TI  - Deletion of hepatic Ctr1 reveals its function in copper acquisition and
      compensatory mechanisms for copper homeostasis.
AB  - Copper is a vital trace element required for normal growth and development of
      many organisms. To determine the roles for copper transporter 1 (Ctr1) in hepatic
      copper metabolism and the contribution of the liver to systemic copper
      homeostasis, we have generated and characterized mice in which Ctr1 is deleted
      specifically in the liver. These mice express less than 10% residual Ctr1 protein
      in the liver and exhibit a small but significant growth retardation, which
      disappears with age. Hepatic copper concentrations and the activities of copper
      requiring enzymes are reduced; however, mild copper deficiency relative to Ctr1
      protein deficit indicates compensatory mechanisms for copper metabolism. Copper
      concentrations of other organs did not alter despite the defect in hepatic copper
      uptake. Whereas biliary copper excretion is reduced, urinary copper concentration
      in these mice is higher than that of control mice. Our data indicate that Ctr1
      plays a critical role in copper acquisition in the liver, and, when Ctr1
      expression is compromised, compensatory mechanisms facilitate copper uptake
      and/or retention in the liver and excretion of copper via urine.

PMID- 19095765
TI  - Ischemia-mediated aggregation of the actin cytoskeleton is one of the major
      initial events resulting in ischemia-reperfusion injury.
AB  - Ischemia-reperfusion (IR) injury represents a major clinical challenge, which
      contributes to morbidity and mortality during surgery. The critical role of
      natural immunoglobulin M (IgM) and complement in tissue injury has been
      demonstrated. However, cellular mechanisms that result in the deposition of
      natural IgM and the activation of complement are still unclear. In this report,
      using a murine intestinal IR injury model, we demonstrated that the beta-actin
      protein in the small intestine was cleaved and actin filaments in the columnar
      epithelial cells were aggregated after a transient disruption during 30 min of
      ischemia. Ischemia also led to deposition of natural IgM and complement 3 (C3). A
      low dose of cytochalasin D, a depolymerization reagent of the actin cytoskeleton,
      attenuated this deposition and also attenuated intestinal tissue injury in a dose
      dependent manner. In contrast, high doses of cytochalasin D failed to worsen the
      injury. These data indicate that ischemia-mediated aggregation of the actin
      cytoskeleton, rather than its disruption, results directly in the deposition of
      natural IgM and C3. We conclude that ischemia-mediated aggregation of the actin
      cytoskeleton leads to the deposition of natural IgM and the activation of
      complement, as well as tissue injury.

PMID- 19095766
TI  - Every slow-wave impulse is associated with motor activity of the human stomach.
AB  - Using a newly developed high-resolution three-dimensional magnetic detector
      system (3D-MAGMA), we observed periodical movements of a small magnetic marker in
      the human stomach at the typical gastric slow-wave frequency, that is 3 min(-1).
      Thus we hypothesized that each gastric slow wave induces a motor response that is
      not strong enough to be detected by conventional methods. Electrogastrographies
      (EGG, Medtronic, Minneapolis, MN) for measurement of gastric slow waves and 3D
      MAGMA (Innovent, Jena, Germany) measurements were simultaneously performed in 21
      healthy volunteers (10 men, 40.4+/-13.6 yr; 11 women, 35.8+/-11.6 yr). The 3D
      MAGMA system contains 27 highly sensitive magnetic field sensors that are able to
      locate a magnetic pill inside a human body with an accuracy of +/-5 mm or less in
      position and +/-2 degrees in orientation at a frequency of 50 Hz. Gastric transit
      time of the magnetic marker ranged from 19 to 154 min. The mean dominant EGG
      frequency while the marker was in the stomach was 2.87+/-0.15 cpm. The mean
      dominant 3D-MAGMA frequency during this interval was nearly identical; that is,
      2.85+/-0.15 movements per minute. We observed a strong linear correlation between
      individual dominant EGG and 3D-MAGMA frequency (R=0.66, P=0.0011). Our findings
      suggest that each gastric slow wave induces a minute contraction that is too
      small to be detected by conventional motility investigations but can be recorded
      by the 3D-MAGMA system. The present slow-wave theory that assumes that the slow
      wave is a pure electrical signal should be reconsidered.

PMID- 19095767
TI  - Dietary glutamine and oral antibiotics each improve indexes of gut barrier
      function in rat short bowel syndrome.
AB  - Short bowel syndrome (SBS) is associated with gut barrier dysfunction. We
      examined effects of dietary glutamine (GLN) or oral antibiotics (ABX) on indexes
      of gut barrier function in a rat model of SBS. Adult rats underwent a 60% distal
      small bowel + proximal colonic resection (RX) or bowel transection (TX; control).
      Rats were pair fed diets with or without l-GLN for 20 days after operation. Oral
      ABX (neomycin, metronidazole, and polymyxin B) were given in some RX rats fed
      control diet. Stool secretory immunoglobulin A (sIgA) was measured serially. On
      day 21, mesenteric lymph nodes (MLN) were cultured for gram-negative bacteria.
      IgA-positive plasma cells in jejunum, stool levels of flagellin- and
      lipopolysaccharide (LPS)-specific sIgA, and serum total, anti-flagellin- and anti
      LPS IgG levels were determined. RX caused gram-negative bacterial translocation
      to MLN, increased serum total and anti-LPS IgG and increased stool total sIgA.
      After RX, dietary GLN tended to blunt bacterial translocation to MLN (-29%, P =
      NS) and significantly decreased anti-LPS IgG levels in serum, increased both
      stool and jejunal mucosal sIgA and increased stool anti-LPS-specific IgA. Oral
      ABX eliminated RX-induced bacterial translocation, significantly decreased total
      and anti-LPS IgG levels in serum, significantly decreased stool total IgA and
      increased stool LPS-specific IgA. Partial small bowel-colonic resection in rats
      is associated with gram-negative bacterial translocation from the gut and a
      concomitant adaptive immune response to LPS. These indexes of gut barrier
      dysfunction are ameliorated or blunted by administration of dietary GLN or oral
      ABX, respectively. Dietary GLN upregulates small bowel sIgA in this model.

PMID- 19095768
TI  - Minireview: latest perspectives on antiinflammatory actions of glucocorticoids.
AB  - Taking into consideration that glucocorticoid (GC) hormones have been used
      clinically for over half a century and that more than 20 yr have passed since the
      cloning of the GC receptor (GR), it is hard to imagine that novel aspects in the
      molecular mechanism by which GCs mediate their antiinflammatory actions are still
      being unveiled today. Partly, this is because almost on a daily basis, novel
      insights arise from parallel fields, e.g. nuclear receptor cofactor and chromatin
      regulation and their concomitant impact on gene transcription events, eventually
      leading to a revisitation or refinement of old hypotheses. On the other hand, it
      does remain striking and puzzling why GCs use different mechanisms in so many
      different cell types and on many different target genes to elicit an
      antiinflammatory effect. Meanwhile, the obvious question for the clinic remains:
      is the separation of GR functionalities through differential ligand design the
      strategy of choice to avoid most GC-mediated side effects? This minireview aims
      to highlight some of the latest findings on aspects of the antiinflammatory
      working mechanisms of GCs.

PMID- 19095769
TI  - Molecular mechanism of action of pharmacoperone rescue of misrouted GPCR mutants:
      the GnRH receptor.
AB  - The human GnRH receptor (hGnRHR), a G protein-coupled receptor, is a useful model
      for studying pharmacological chaperones (pharmacoperones), drugs that rescue
      misfolded and misrouted protein mutants and restore them to function. This
      technique forms the basis of a therapeutic approach of rescuing mutants
      associated with human disease and restoring them to function. The present study
      relies on computational modeling, followed by site-directed mutagenesis,
      assessment of ligand binding, effector activation, and confocal microscopy. Our
      results show that two different chemical classes of pharmacoperones act to
      stabilize hGnRHR mutants by bridging residues D(98) and K(121). This ligand
      mediated bridge serves as a surrogate for a naturally occurring and highly
      conserved salt bridge (E(90)-K(121)) that stabilizes the relation between
      transmembranes 2 and 3, which is required for passage of the receptor through the
      cellular quality control system and to the plasma membrane. Our model was used to
      reveal important pharmacophoric features, and then identify a novel chemical
      ligand, which was able to rescue a D(98) mutant of the hGnRHR that could not be
      rescued as effectively by previously known pharmacoperones.

PMID- 19095770
TI  - Estrogen-mediated suppression of the gene encoding protein tyrosine phosphatase
      PTPRO in human breast cancer: mechanism and role in tamoxifen sensitivity.
AB  - We have previously demonstrated the tumor suppressor characteristics of protein
      tyrosine phosphatase receptor-type O (PTPRO) in leukemia and lung cancer,
      including its suppression by promoter methylation. Here, we show tumor-specific
      methylation of the PTPRO CpG island in primary human breast cancer. PTPRO
      expression was significantly reduced in established breast cancer cell lines MCF
      7 and MDA-MB-231 due to promoter methylation compared with its expression in
      normal human mammary epithelial cells (48R and 184). Further, the silenced gene
      could be demethylated and reactivated in MCF-7 and MDA-MB-231 cells upon
      treatment with 5-Azacytidine, a DNA hypomethylating agent. Because PTPRO promoter
      harbors estrogen-responsive elements and 17beta-estradiol (E2) plays a role in
      breast carcinogenesis, we examined the effect of E2 and its antagonist tamoxifen
      on PTPRO expression in human mammary epithelial cells and PTPRO-expressing breast
      cancer cell line Hs578t. Treatment with E2 significantly curtailed PTPRO
      expression in 48R and Hs578t cells, which was facilitated by ectopic expression
      of estrogen receptor (ER)beta but not ERalpha. On the contrary, treatment with
      tamoxifen increased PTPRO expression. Further, knockdown of ERbeta by small
      interfering RNA abolished these effects of E2 and tamoxifen. Chromatin
      immunoprecipitation assay showed association of c-Fos and c-Jun with PTPRO
      promoter in untreated cells, which was augmented by tamoxifen-mediated
      recruitment of ERbeta to the promoter. Estradiol treatment resulted in
      dissociation of c-Fos and c-Jun from the promoter. Ectopic expression of PTPRO in
      the nonexpressing MCF-7 cells sensitized them to growth-suppressive effects of
      tamoxifen. These data suggest that estrogen-mediated suppression of PTPRO is
      probably one of the early events in estrogen-induced tumorigenesis and that
      expression of PTPRO could facilitate endocrine therapy of breast cancer.

PMID- 19095771
TI  - PAPA-1 Is a nuclear binding partner of IGFBP-2 and modulates its growth-promoting
      actions.
AB  - IGF-binding proteins (IGFBPs) have multiple cellular effects, which occur by both
      IGF-dependent and -independent mechanisms. IGFBP-2 is involved in the regulation
      of both normal and carcinogenic cell growth. To further understand the actions of
      IGFBP-2, we carried out a yeast two-hybrid screen to search for intracellular
      partner proteins using a human prostate cDNA library. We isolated Pim-1
      associated protein-1 (PAP-1)-associated protein-1 (PAPA-1) as an IGFBP-2-binding
      protein, whose expression and subcellular localization is regulated by both IGFBP
      2 and androgens. Coimmunoprecipitation and glutathione S-transferase pull-down
      assay confirmed the interaction in vitro, and confocal microscopy showed the
      colocalization of IGFBP-2 and PAPA-1 in the nucleus. Suppression of PAPA-1 by
      small interfering RNA treatment enhanced the growth-promoting effect of IGFBP-2.
      Conversely, IGFBP-2-promoted bromodeoxyuridine incorporation into LNCaP cells was
      abrogated by the simultaneous overexpression of myc-hPAPA-1. Mouse embryonic
      fibroblasts from IGFBP-2 knockout mouse showed diminished growth activity
      compared with wild type, and expression of FLAG-mPAPA-1 decreased cell
      proliferation in IGFBP-2 knockout, but not control mouse embryonic fibroblasts.
      These studies suggest that the growth-promoting role of IGFBP-2 in prostate
      cancer is inhibited by its intracellular interaction with PAPA-1.

PMID- 19095772
TI  - Proteasome regulation of dynamic transcription factor occupancy on the GnRH
      stimulated luteinizing hormone beta-subunit promoter.
AB  - GnRH is the main modulator of LH secretion and transcription of the LH subunit
      genes in pituitary gonadotropes. The LHbeta gene is preferentially transcribed
      during pulsatile GnRH stimuli of one pulse/30 min and is thus carefully
      controlled by specific signaling pathways and transcription factors. We now show
      that GnRH-stimulated LHbeta transcription is also influenced by the ubiquitin
      proteasome system. GnRH-stimulated activity of an LHbeta reporter gene was
      prevented by proteasome inhibitors MG-132 and lactacystin. Inhibition was not
      rescued by overexpression of two key transcription factors for LHbeta, early
      growth response-1 (Egr-1) and steroidogenic factor-1 (SF-1). Increased endogenous
      LHbeta transcription after GnRH treatment was also prevented by MG-132, as
      measured by primary transcript assays. To investigate possible mechanisms of
      LHbeta transcriptional inhibition by proteasome blockade, we employed chromatin
      immunoprecipitation to measure LHbeta promoter occupancy by transcription
      factors. Without GnRH, binding was low and unorganized. With GnRH, Egr-1 and SF-1
      associations were stimulated, cyclic, and coincidental, with a period of
      approximately 30 min. MG-132 disrupted GnRH-induced Egr-1 and SF-1 binding and
      prevented phosphorylated RNA polymerase II association with the LHbeta promoter.
      Egr-1, but not SF-1, protein was induced by GnRH and accumulated with MG-132. Egr
      1 and SF-1 were ubiquitinated in gonadotropes and ubiquitinated forms of these
      factors associated with the LHbeta promoter, suggesting their degradation may be
      key for LHbeta proteasome-dependent transcription. Together, these results
      demonstrate that degradation via the proteasome is vital to GnRH-stimulated
      LHbeta expression, and this occurs in part by allowing proper transcription
      factor associations with the LHbeta promoter.

PMID- 19095774
TI  - Direct bacterial profiling by matrix-assisted laser desorption-ionization time-of
      flight mass spectrometry for identification of pathogenic Neisseria.
AB  - The present study investigates the suitability of direct bacterial profiling as a
      tool for the identification and subtyping of pathogenic Neisseria. The genus
      Neisseria includes two human pathogens, Neisseria meningitidis and Neisseria
      gonorrhoeae, as well as several nonpathogenic Neisseria species. Here, a matrix
      assisted laser desorption/ionization time-of-flight mass spectrometry profiling
      protocol was optimized using a laboratory strain of E. coli DH5alpha to guarantee
      high quality and reproducible results. Subsequently, mass spectra for both
      laboratory and clinical strains of N. gonorrhoeae, N. meningitidis, and several
      nonpathogenic Neisseria species were collected. Significant interspecies
      differences but little intraspecies diversity were revealed by means of a visual
      inspection and bioinformatics examination using the MALDI BioTyper software.
      Cluster analysis successfully separated mass spectra collected from three groups
      that corresponded to N. gonorrhoeae, N. meningitidis, and nonpathogenic Neisseria
      isolates. Requiring only one bacterial colony for testing and using a fast and
      easy measuring protocol, this approach represents a powerful tool for the rapid
      identification of pathogenic Neisseria and can be adopted for other
      microorganisms.

PMID- 19095773
TI  - Laboratory practice guidelines for detecting and reporting BCR-ABL drug
      resistance mutations in chronic myelogenous leukemia and acute lymphoblastic
      leukemia: a report of the Association for Molecular Pathology.
AB  - The BCR-ABL tyrosine kinase produced by the t(9;22)(q34;q11) translocation, also
      known as the Philadelphia chromosome, is the initiating event in chronic myeloid
      leukemia (CML) and Ph+ acute lymphoblastic leukemia (ALL). Targeting of BCR-ABL
      with tyrosine kinase inhibitors (TKIs) has resulted in rapid clinical responses
      in the vast majority of patients with CML and Philadelphia chromosome+ ALL.
      However, long-term use of TKIs occasionally results in emergence of therapy
      resistance, in part through the selection of clones with mutations in the BCR-ABL
      kinase domain. We present here an overview of the current practice in monitoring
      for such mutations, including the methods used, the clinical and laboratory
      criteria for triggering mutational analysis, and the guidelines for reporting BCR
      ABL mutations. We also present a proposal for a public database for correlating
      mutational status with in vitro and in vivo responses to different TKIs to aid in
      the interpretation of mutation studies.

PMID- 19095775
TI  - Multi-probe real-time PCR identification of common Mycobacterium species in blood
      culture broth.
AB  - Mycobacterium tuberculosis complex, M. avium, and M. intracellulare are the most
      common causes of systemic bacterial infection in AIDS patients. To identify these
      mycobacterial isolates in primary blood culture broths, we developed a multiple
      hybridization probe-based real-time PCR assay using the LightCycler system. The
      primers were designed to amplify a 320-bp fragment of Mycobacterium 16S rRNA
      genes. Reaction specificity was evaluated using PCR amplification curves along
      with specific melting temperatures of probes on DNA extracted from 13
      Mycobacterium species. In this study, results showed 100% accuracy for the
      selected bacterial panel. Detection limits were 350, 600, and 650 colony-forming
      unit (CFU)/ml blood culture broths for M. tuberculosis complex, M. avium, and M.
      intracellulare, respectively (1 to 2 CFU/reaction). To evaluate clinical
      applicability, 341 acid-fast bacilli in blood culture broths were analyzed. In
      total, 327 (96%) were positively identified: 54.5% M. tuberculosis complex, 37.5%
      M. avium, and 3.8% M. intracellulare. Results can be available within 3 hours of
      receiving a broth sample, which makes this rapid and simple assay an attractive
      diagnostic tool for clinical use.

PMID- 19095776
TI  - Progression-free survival and time to progression as primary end points in
      advanced breast cancer: often used, sometimes loosely defined.
AB  - BACKGROUND: The growing availability of active agents makes the development of
      novel therapies increasingly complex and the choice of end points critical. We
      assessed the frequency of use of efficacy end points in advanced breast cancer.
      METHODS: We searched PubMed for randomized trials published between 2000 and 2007
      in 10 leading medical journals. We abstracted data on progression-free survival
      (PFS), time to tumor progression (TTP), response rate (RR) and overall survival.
      RESULTS: A total of 58 studies enrolled 23,371 assessable patients in 122
      treatment arms. The primary end points most frequently used were RR and TTP (n=21
      each), followed by PFS (n=14). In five of the trials using TTP as the primary end
      point, no definition of TTP was reported; in 13 of the other 16 cases, death was
      counted as an event, making TTP indistinguishable from PFS. Trials having PFS,
      TTP or time to treatment failure as the primary end point (n=36) had a higher
      mean number of patients than those using RR (P=0.061). CONCLUSION: Investigators
      seem to be frequently using PFS and TTP interchangeably in advanced breast
      cancer. Such use of terms may lead to confusion when results of different trials
      are compared, and uniform use of definitions seems in order.

PMID- 19095777
TI  - Epidermal growth factor receptor gene copy number, K-ras mutation and
      pathological response to preoperative cetuximab, 5-FU and radiation therapy in
      locally advanced rectal cancer.
AB  - BACKGROUND: Cetuximab improves activity of chemotherapy in metastatic colorectal
      cancer (mCRC). Gene copy number (GCN) of epidermal growth factor receptor (EGFR)
      has been suggested to be a predictive factor of response to cetuximab in patients
      (pts) with mCRC; on the contrary, K-ras mutation has been associated with
      cetuximab resistance. PATIENTS AND METHODS: We have conducted a phase II study
      with cetuximab administered weekly for 3 weeks as single agent and then with 5
      fluorouracil and radiation therapy as neo-adjuvant treatment for locally advanced
      rectal cancer (LARC). EGFR immunohistochemistry expression, EGFR GCN and K-ras
      mutation were evaluated on diagnostic tumor biopsy. Dworak's tumor regression
      grade (TRG) was evaluated on surgical specimens. RESULTS: Forty pts have been
      treated; 39 pts are assessable. TRG 3 and 4 were achieved in nine (23.1%) and
      three pts (7.7%) respectively; TRG 3-4 rate was 55% and 5.3% in case of high and
      low GCN, respectively (P 0.0016). Pts with K-ras mutated tumors had lower rate of
      high TRG: 11% versus 36.7% (P 0.12). In pts with wild-type K-ras, TRG 3-4 rate
      was 58.8% versus 7.7% in case of high or low GCN, respectively (P 0.0012).
      CONCLUSIONS: In pts with LARC, EGFR GCN is predictive of high TRG to cetuximab
      plus 5-FU radiotherapy. Moreover, our data suggest that a wild-type K-ras
      associated with a high EGFR GCN can predict sensitivity to cetuximab-based
      treatment.

PMID- 19095778
TI  - Relationship of adiposity with arterial stiffness as mediated by adiponectin in
      older men and women: the Hoorn Study.
AB  - OBJECTIVE: To investigate whether adiponectin is associated with arterial
      stiffness, and whether adiponectin explains the association between body
      composition and arterial stiffness. DESIGN: Cross-sectional cohort study.
      METHODS: Subjects were participants (n=456, mean age 68.9+/-6.1 years; age range
      60-86 years) of the third follow-up examination of the Hoorn Study. Trunk fat,
      leg fat, trunk lean, and leg lean mass were measured by dual-energy X-ray
      absorptiometry. Ultrasound was used to measure distensibility and compliance of
      the carotid, femoral, and brachial arteries, and carotid Young's elastic modulus
      (as estimates of peripheral arterial stiffness). Results Trunk fat mass was
      negatively associated with (ln-transformed) adiponectin (standardized beta=-0.49,
      P<0.001), while leg fat mass was positively associated with adiponectin
      (beta=0.44, P<0.001), after adjustment for each other, age, and lean mass. After
      adjustment for age, sex, mean arterial pressure, and estimated glomerular
      filtration rate, higher adiponectin was associated with decreased peripheral
      arterial stiffness (beta of mean Z-scores of all three arteries=0.14, P=0.001).
      However, the associations of trunk fat (beta=-0.26, P<0.001) and leg fat
      (beta=0.16, P=0.006) with peripheral arterial stiffness were only minimally
      explained by adiponectin levels. CONCLUSION: Trunk fat and leg fat are oppositely
      associated with adiponectin. Although low adiponectin was a determinant of
      increased peripheral arterial stiffness, it only explained a small part of the
      association between body fat and peripheral arterial stiffness. This indicated
      that factors other than adiponectin may be more important in the
      pathophysiological mechanisms by which abdominal obesity leads to arterial
      stiffness.

PMID- 19095779
TI  - Thyroid dysfunction and kidney disease.
AB  - Thyroid hormones (TH) are essential for an adequate growth and development of the
      kidney. Conversely, the kidney is not only an organ for metabolism and
      elimination of TH, but also a target organ of some of the iodothyronines'
      actions. Thyroid dysfunction causes remarkable changes in glomerular and tubular
      functions and electrolyte and water homeostasis. Hypothyroidism is accompanied by
      a decrease in glomerular filtration, hyponatremia, and an alteration of the
      ability for water excretion. Excessive levels of TH generate an increase in
      glomerular filtration rate and renal plasma flow. Renal disease, in turn, leads
      to significant changes in thyroid function. The association of different types of
      glomerulopathies with both hyper- and hypofunction of the thyroid has been
      reported. Less frequently, tubulointerstitial disease has been associated with
      functional thyroid disorders. Nephrotic syndrome is accompanied by changes in the
      concentrations of TH due primarily to loss of protein in the urine. Acute kidney
      injury and chronic kidney disease are accompanied by notable effects on the
      hypothalamus-pituitary-thyroid axis. The secretion of pituitary thyrotropin (TSH)
      is impaired in uremia. Contrary to other non-thyroidal chronic disease, in
      uraemic patients it is not unusual to observe the sick euthyroid syndrome with
      low serum triodothyronine (T(3)) without elevation of reverse T(3) (rT(3)). Some
      authors have reported associations between thyroid cancer and kidney tumors and
      each of these organs can develop metastases into the other. Finally, data from
      recent research suggest that TH, especially T(3), can be considered as a marker
      for survival in patients with kidney disease.

PMID- 19095780
TI  - Incidence and prevalence of nutritional and hereditary rickets in southern
      Denmark.
AB  - OBJECTIVE: To estimate the incidence of nutritional rickets and the incidence and
      prevalence of hereditary rickets. DESIGN: Population-based retrospective cohort
      study based on a review of medical records. METHODS: Patients aged 0-14.9 years
      referred to or discharged from hospitals in southern Denmark from 1985 to 2005
      with a diagnosis of rickets were identified by register search, and their medical
      records were retrieved. Patients fulfilling the diagnostic criteria of primary
      rickets were included. RESULTS: We identified 112 patients with nutritional
      rickets of whom 74% were immigrants. From 1995 to 2005, the average incidence of
      nutritional rickets in children aged 0-14.9 and 0-2.9 years was 2.9 and 5.8 per
      100,000 per year respectively. Among immigrant children born in Denmark, the
      average incidence was 60 (0-14.9 years) per 100,000 per year. Ethnic Danish
      children were only diagnosed in early childhood and the average incidence in the
      age group 0-2.9 years declined from 5.0 to 2.0 per 100,000 per year during 1985
      1994 to 1995-2005. Sixteen cases of hereditary rickets were diagnosed during the
      study period giving an average incidence of 4.3 per 100,000 (0-0.9 years) per
      year. The prevalence of hypophosphatemic rickets and vitamin D-dependent rickets
      type 1 was 4.8 and 0.4 per 100,000 (0-14.9 years) respectively. CONCLUSIONS:
      Nutritional rickets is rare in southern Denmark and largely restricted to
      immigrants, but the incidence among ethnic Danish children was unexpectedly high.
      Hereditary rickets is the most common cause of rickets in ethnic Danish children,
      but nutritional rickets is most frequent among all young children.

PMID- 19095781
TI  - Intrauterine growth restriction and adult disease: the role of adipocytokines.
AB  - Intrauterine growth restriction (IUGR) is the failure of the fetus to achieve
      his/her intrinsic growth potential, due to anatomical and/or functional disorders
      and diseases in the feto-placental-maternal unit. IUGR results in significant
      perinatal and long-term complications, including the development of insulin
      resistance/metabolic syndrome in adulthood. The thrifty phenotype hypothesis
      holds that intrauterine malnutrition leads to an adaptive response that alters
      the fetal metabolic and hormonal milieu designed for intrauterine survival. This
      fetal programming predisposes to an increased susceptibility for chronic
      diseases. Although the mechanisms controlling intrauterine growth are poorly
      understood, adipose tissue may play an important role in linking poor fetal
      growth to the subsequent development of adult diseases. Adipose tissue secretes a
      number of hormones, called adipocytokines, important in modulating metabolism and
      recently involved in intrauterine growth. This review aims to summarize reported
      findings concerning the role of adipocytokines (leptin, adiponectin, ghrelin,
      tumor necrosis factor (TNF), interleukin-6 (IL6), visfatin, resistin, apelin) in
      early life, while attempting to speculate mechanisms through which differential
      regulation of adipocytokines in IUGR may influence the risk for development of
      chronic diseases in later life.

PMID- 19095782
TI  - Hepatocellular carcinoma with a pseudocapsule on gadolinium-enhanced MR images:
      correlation with histopathologic findings.
AB  - PURPOSE: To evaluate the characteristics of hepatocellular carcinoma (HCC) with a
      pseudocapsule on dynamic magnetic resonance (MR) images. MATERIALS AND METHODS:
      The institutional review board approval was obtained, and the requirements for
      informed consent were waived for this retrospective study. Dynamic MR studies of
      surgically resected 106 HCCs in 93 patients were retrospectively reviewed. A
      false-positive fibrous capsule (FC) on dynamic MR images was considered to be a
      pseudocapsule. Pathologic specimens of HCCs with a pseudocapsule were reviewed.
      The differences in size, tumor grade, the degree of liver fibrosis and background
      liver diseases, and the incidence of vascular invasion were compared between HCCs
      with a pseudocapsule on MR images and those with FC at histologic examination by
      using Student t, Kruskal-Wallis, and chi(2) tests. RESULTS: The sensitivity,
      specificity, and accuracy of dynamic MR in the diagnosis of histologic FC were
      94.0% (47 of 50), 73.2% (41 of 56), and 83.0% (88 of 106), respectively. There
      were 15 (14.2%) HCCs with a pseudocapsule. The pathologic specimens suggested
      possible causes of the pseudocapsule that included prominent sinusoids (n = 6),
      peritumoral fibrosis mimicking bridging fibrosis (n = 3), and both (n = 5). In
      one case, the capsulated HCC was surrounded by a well-differentiated HCC
      component. The mean size of a HCC with a pseudocapsule tended to be smaller than
      that with histologic FC, although it was not significant (mean +/- standard
      deviation: 2.8 cm +/- 1.0 vs 3.5 cm +/- 2.0, P = .09). Liver cirrhosis was less
      frequent in HCCs with a pseudocapsule than in those with a histologic FC (one of
      14 [7.1%] vs 20 of 49 [40.8%], P < .05). The tumor grades were not significantly
      different, and the incidence of vascular invasion after standardizing the tumor
      size (<or=4 cm) was similar (five of 14 [35.7%] vs 12 of 37 [32.4%]). CONCLUSION:
      Dynamic MR imaging is accurate in depicting FC in HCCs. HCC with a pseudocapsule
      at MR possibly consists of peritumoral sinusoids and/or fibrosis. The
      pseudocapsule may be similar to histologic FC in terms of tumor invasiveness.

PMID- 19095783
TI  - Mapping the zonal organization of tumor perfusion and permeability in a rat
      glioma model by using dynamic contrast-enhanced synchrotron radiation CT.
AB  - PURPOSE: To depict and analyze in vivo the tumor zone organization of C6 gliomas
      depicted on quantitative parametric maps obtained with dynamic contrast material
      enhanced synchrotron radiation computed tomography (CT) in a tightly controlled
      data-processing protocol. MATERIALS AND METHODS: Animal use was compliant with
      official French guidelines and was assessed by the local Internal Evaluation
      Committee for Animal Welfare and Rights. Fifteen Wistar rats with orthotopically
      implanted gliomas were studied at monochromatic synchrotron radiation CT after
      receiving a bolus injection of contrast material. The iodine concentration maps
      were analyzed by using a compartmental model selected from among a package of
      models. Choice of model and assessment of the relevance of the model were guided
      by quality criteria. Tissue blood flow (F(T)), tissue blood volume fraction
      (V(T)), permeability-surface area product (PS), artery-to-tissue delay (D(A-T)),
      and vascular mean transit time (MTT) maps were obtained. Parametric map findings
      were compared with histologic findings. Local regions of interest were selected
      in the contralateral hemisphere and in several tumor structures to characterize
      the tumor microvasculature. Differences in parameter values between regions were
      assessed with the Wilcoxon method. RESULTS: Whole-tumor parameters were expressed
      as means +/- standard errors of the mean: Mean F(T), V(T), PS, and D(A-T) values
      and MTT were 61.4 mL/min/100 mL +/- 15.3, 2.4% +/- 0.4, 0.37 mL/min/100 mL +/-
      0.11, 0.24 second +/- 0.06; and 3.9 seconds +/- 0.83, respectively. MTT and mean
      PS were significantly lower (P < .01) in the normal contralateral tissue: 1.10
      seconds +/- 0.06 and < or = 10(-5) mL/min/100 mL, respectively. Tumor regions
      were characterized by significantly different (P < .05) F(T) and V(T) pairs: 108
      mL/min/100 mL and 3.66%, respectively, at the periphery; 45.9 mL/min/100 mL and
      1.91%, respectively, in the intermediate zone; 5.1 mL/min/100 mL and 0.42%,
      respectively, in the center; and 210 mL/min/100 mL and 6.82%, respectively, in
      the maximal value region. CONCLUSION: Fine mapping of the glioma microcirculation
      is feasible with dynamic contrast-enhanced synchrotron radiation CT performed
      with well-controlled analytic protocols. SUPPLEMENTAL MATERIAL:
      http://radiology.rsnajnls.org/cgi/content/full/2501071929/DC1.

PMID- 19095784
TI  - Pancreatic endocrine tumors: tumor blood flow assessed with perfusion CT reflects
      angiogenesis and correlates with prognostic factors.
AB  - PURPOSE: To prospectively correlate multidetector computed tomographic (CT)
      perfusion measurement of pancreatic endocrine tumors with tumor microvascular
      density (MVD) assessed by using histologic techniques and to determine whether
      perfusion CT parameters differ between tumor grades. MATERIALS AND METHODS:
      Institutional review board approval and informed consent were obtained. Thirty
      six patients (15 men, 21 women; mean age, 53 years; range, 18-78 years) with
      resectable pancreatic endocrine tumors underwent presurgical dynamic perfusion
      CT. Twenty-eight (78%) of 36 patients were included in the study group; eight
      were excluded because of artifacts that were not compatible with perfusion
      postprocessing. Multidetector CT perfusion data were analyzed to calculate tumor
      and normal pancreatic blood flow, blood volume, mean transit time, and
      permeability-surface area product. Multidetector CT perfusion parameters were
      compared with intratumoral MVD by using the Spearman correlation coefficient and
      with World Health Organization (WHO) classification, tumor size, tumor
      proliferation index, hormonal profile, and presence of metastases by using Mann
      Whitney tests. RESULTS: High correlation (r = 0.620, P < .001) was observed
      between tumor blood flow and intratumoral MVD. Blood flow was significantly
      higher (P = .02) in the group of benign tumors (WHO 1) than in the groups of
      tumors of indeterminate prognosis (WHO 2) or well-differentiated carcinomas (WHO
      3). Blood flow was significantly higher in tumors with a proliferation index of
      2% or less (P = .005) and in those without histologic signs of microscopic
      vascular involvement (P = .008). Mean transit time was longer in tumors with
      lymph node (P = .02) or liver (P = .05) metastasis. CONCLUSION: Perfusion CT is
      feasible in patients with pancreatic endocrine tumors and reflects MVD. Perfusion
      CT measurements are correlated with histoprognostic factors, such as
      proliferation index and WHO classification.

PMID- 19095785
TI  - Staging of T3 and T4 gastric carcinoma with multidetector CT: added value of
      multiplanar reformations for prediction of adjacent organ invasion.
AB  - PURPOSE: To determine the added value of multiplanar reformation (MPR) images
      combined with computed tomographic (CT) images in staging of T4 gastric cancers.
      MATERIALS AND METHODS: The institutional review board approved this retrospective
      study and waived informed consent. One hundred forty-nine consecutive patients
      (99 men [age range, 33-85 years; mean age, 63.1 years] and 50 women [age range,
      30-85 years; mean age, 57.1 years]; age range, 30-85 years; mean age, 61.1 years)
      with pathologically and/or surgically confirmed T3 (n = 110) or T4 tumors (n =
      39), with invasion of the transverse colon or mesocolon (n = 23), pancreas (n =
      16), diaphragm (n = 4), liver (n = 3), and/or spleen (n = 1) were included. Two
      experienced radiologists independently reviewed 4-mm-thick transverse CT images
      and, 10 weeks later, reviewed both transverse CT and additional coronal and
      sagittal MPR images to assess tumor invasion in each of the aforementioned five
      adjacent organs. Receiver operating characteristic (ROC) analyses and weighted
      kappa statistics were obtained to evaluate reader performance and agreement in
      identifying tumor invasion. RESULTS: With addition of MPR images, the area under
      the ROC curve (AUC) led to a significant increase in the prediction of adjacent
      organ invasion in per-organ analyses (0.88 vs 0.95 for reader 1 [P = .01], 0.88
      vs 0.98 for reader 2 [P < .001]) and identification of T4 tumors in per-patient
      analyses (0.79 vs 0.91 for reader 1 [P = .006], 0.78 vs 0.96 for reader 2 [P <
      .001]). In the five analyzed organs, AUC was significantly increased in regard to
      invasion of the transverse colon or mesocolon and pancreas; separate analysis was
      not performed for the diaphragm, liver, and spleen because of the small number of
      true invasions. Interobserver agreement increased in per-organ (kappa = 0.43 vs
      0.67) and per-patient (kappa = 0.42 vs 0.62) analyses. CONCLUSION: Adding MPR
      images to transverse CT images improves the capability for distinguishing T3 from
      T4 gastric cancer and prediction of adjacent organ invasion. SUPPLEMENTAL
      MATERIAL: http://radiology.rsnajnls.org/cgi/content/full/2502071872/DC1.

PMID- 19095786
TI  - Short- and midterm reproducibility of apparent diffusion coefficient measurements
      at 3.0-T diffusion-weighted imaging of the abdomen.
AB  - PURPOSE: To test the hypothesis that there is no significant variability in
      apparent diffusion coefficients (ADCs) at assessment of the short- and midterm
      reproducibility of ADC measurements in a healthy population. MATERIALS AND
      METHODS: Twenty healthy male volunteers were enrolled in this prospective
      institutional review board-approved study after they provided written informed
      consent. A 3.0-T magnetic resonance (MR) system was used to perform five axial
      diffusion-weighted (DW) abdominal acquisitions (session 1). A mean of 147 days +/
      20 (standard deviation) later, 16 of the 20 volunteers were imaged again with
      use of the same protocol and MR system (session 2). The mean ADCs for three
      regions of interest (ROIs) in five anatomic locations (right hepatic lobe,
      spleen, and head, body, and tail of pancreas) were calculated. The coefficient of
      variation (CV, equal to standard deviation divided by mean) was calculated for
      each subject, session, and anatomic location. The ADC and CV data were then
      analyzed by using repeated-measures analysis of variance. RESULTS: There were
      significant differences (P < .001) in mean ADCs among the five anatomic
      locations. There were no significant differences in ADCs among the various
      repeated sequence acquisitions or the three ROIs. There were no significant
      differences in ADCs between imaging sessions 1 and 2. ADCs were fairly stable
      over the midterm within a given individual. Finally, there were no significant
      differences in resulting CVs between the imaging sessions or anatomic locations.
      The mean CV for ADC measurement reproducibility was 14% (95% confidence interval:
      13%, 15%). CONCLUSION: The mean CV for short- and midterm ADC reproducibility was
      14% at abdominal DW imaging. Treatment effects of less than approximately 27%
      (change in ADC divided by pretreatment ADC) will not be clinically detectable
      with confidence with one acquisition in a single individual.

PMID- 19095787
TI  - Spin-echo echo-planar perfusion MR imaging in the differential diagnosis of
      solitary enhancing brain lesions: distinguishing solitary metastases from primary
      glioma.
AB  - Unlike the more widely reported gradient-echo echo-planar perfusion-weighted
      imaging (EPI-PWI) technique, spin-echo (SE) EPI relative cerebral blood volume
      maps select for blood volume in microvessels <8 microm in diameter. This first
      report of SE-EPI PWI for distinguishing brain metastasis from high-grade glioma
      demonstrated 88% sensitivity and 72% specificity in 83 patients. We discuss
      differences in microvessel architecture between high-grade glioma and brain
      metastasis that may explain the surprising success of SE-EPI in this application
      and may deserve further investigation.

PMID- 19095788
TI  - Proton MR spectroscopy improves discrimination between tumor and pseudotumoral
      lesion in solid brain masses.
AB  - BACKGROUND AND PURPOSE: Differentiating between tumors and pseudotumoral lesions
      by conventional MR imaging may be a challenging question. This study aims to
      evaluate the potential usefulness and the added value that single-voxel proton MR
      spectroscopy could provide on this discrimination. MATERIALS AND METHODS: A total
      of 84 solid brain lesions were retrospectively included in the study (68 glial
      tumors and 16 pseudotumoral lesions). Single-voxel spectra at TE 30 ms (short TE)
      and 136 ms (long TE) were available in all cases. Two groups were defined:
      "training-set" (56 cases) and "test-set" (28 cases). Tumors and pseudotumors were
      compared in the training-set with the Mann-Whitney U test. Ratios between
      resonances were defined as classifiers for new cases, and thresholds were
      selected with receiver operating characteristic (ROC) curves. The added value of
      spectroscopy was evaluated by 5 neuroradiologists and assessed with the Wilcoxon
      signed-rank test. RESULTS: Differences between tumors and pseudotumors were found
      in myo-inositol (mIns); P < .01) at short TE, and N-acetylaspartate (NAA; P <
      .001), glutamine (Glx; P < .01), and choline (CHO; P < .05) at long TE.
      Classifiers suggested tumor when mIns/NAA ratio was more than 0.9 at short TE and
      also when CHO/NAA ratio was more than 1.9 at long TE. Classifier accuracy was
      tested in the test-set with the following results: short TE, 82% (23/28); long
      TE, 79% (22/28). The neuroradiologists' confidence rating of the test-cases on a
      5-point scale (0-4) improved between 5% (from 2.86-3) and 27% (from 2.25-2.86)
      with spectroscopy (mean, 17%; P < .01). CONCLUSIONS: The proposed ratios of
      mIns/NAA at short TE and CHO/NAA at long TE provide valuable information to
      discriminate between brain tumor and pseudotumor by improving neuroradiologists'
      accuracy and confidence.

PMID- 19095789
TI  - Imaging lesions of the cavernous sinus.
AB  - Our aim was to review the imaging findings of relatively common lesions involving
      the cavernous sinus (CS), such as neoplastic, inflammatory, and vascular ones.
      The most common are neurogenic tumors and cavernoma. Tumors of the nasopharynx,
      skull base, and sphenoid sinus may extend to the CS as can perineural and
      hematogenous metastases. Inflammatory, infective, and granulomatous lesions show
      linear or nodular enhancement of the meninges of the CS but often have
      nonspecific MR imaging features. In many of these cases, involvement elsewhere
      suggests the diagnosis. MR imaging is sensitive for detecting vascular lesions
      such as carotid cavernous fistulas, aneurysms, and thromboses.

PMID- 19095790
TI  - MR imaging features of isolated cortical vein thrombosis: diagnosis and follow
      up.
AB  - BACKGROUND AND PURPOSE: To our knowledge, very few MR imaging data have been
      reported in isolated cortical venous thrombosis (ICoVT). The purpose of this
      study was to describe MR imaging features, including T2*gradient-echo (GE)
      sequence, in presumed ICoVT. MATERIALS AND METHODS: MR imaging examinations were
      performed in 8 patients with ICoVT (MR venography was performed in all patients
      and digital substraction angiography in 4) at the time of diagnosis and during
      the follow-up at 15 days (4 patients) and at 3 (8 patients), 6 (6 patients), 12
      (3 patients), and 18 months (1 patient). We assessed the presence of a magnetic
      susceptibility effect (MSE) on T2*GE imaging at each site of cerebral venous
      thrombosis and the presence or absence of a normal flow void and iso-, hypo-, or
      hyperintense signal intensity on T1, T2, diffusion-weighted imaging (DWI), and
      fluid-attenuated inversion recovery (FLAIR) images. Parenchymal signal-intensity
      changes were also assessed on the same sequences. RESULTS: MSE was detected on
      T2*GE imaging at the site of a cortical vein in all subjects at the first MR
      imaging examination. The occluded vein appeared as hyperintense in 3 patients,
      iso- to slightly hyperintense in 1 on T1, hypointense in 6 on FLAIR images, and
      as signal-intensity loss on DWI in 3. At follow-up, persisting signal-intensity
      abnormalities on T2*GE imaging were detected at the venous sites in all patients,
      whereas signal-intensity changes on T1- and T2-weighted images were no longer
      present. Parenchymal hyperintensities on FLAIR and DWI (increased apparent
      diffusion coefficient [ADC]) were observed in close vicinity to the thrombosis in
      6/8 patients. Petechial hemorrhages (n = 3) or hematoma (n = 2) was present on
      T2*GE imaging in 5/8 patients. During the follow-up, all cerebral tissue signal
      intensity changes on T1, T2, and FLAIR images decreased both in volume and
      intensity. ADC values normalized within the tissue after 3 months in all
      patients. CONCLUSIONS: On T2*GE imaging, MSE of hemoglobin products within the
      thrombus was observed both at the early and late phases of ICoVT and appears to
      be of high diagnostic value compared with the other signal intensity changes
      detected on standard MR imaging.

PMID- 19095791
TI  - 3D CT evaluation of common crus aplasia.
AB  - Aplasia of the common crus is an uncommon congenital anomaly. We present the case
      of a patient with common crus aplasia and discuss the relevant embryology and the
      role of 3D CT in evaluation of this rare congenital anomaly.

PMID- 19095792
TI  - The neuronal connexin36 interacts with and is phosphorylated by CaMKII in a way
      similar to CaMKII interaction with glutamate receptors.
AB  - Electrical synapses can undergo activity-dependent plasticity. The
      calcium/calmodulin-dependent kinase II (CaMKII) appears to play a critical role
      in this phenomenon, but the underlying mechanisms of how CaMKII affects the
      neuronal gap junction protein connexin36 (Cx36) are unknown. Here we demonstrate
      effective binding of (35)S-labeled CaMKII to 2 juxtamembrane cytoplasmic domains
      of Cx36 and in vitro phosphorylation of this protein by the kinase. Both domains
      reveal striking similarities with segments of the regulatory subunit of CaMKII,
      which include the pseudosubstrate and pseudotarget sites of the kinase. Similar
      to the NR2B subunit of the NMDA receptor both Cx36 binding sites exhibit
      phosphorylation-dependent interaction and autonomous activation of CaMKII. CaMKII
      and Cx36 were shown to be significantly colocalized in the inferior olive, a
      brainstem nucleus highly enriched in electrical synapses, indicating physical
      proximity of these proteins. In analogy to the current notion of NR2B interaction
      with CaMKII, we propose a model that provides a mechanistic framework for CaMKII
      and Cx36 interaction at electrical synapses.

PMID- 19095793
TI  - Failure of T cell homing, reduced CD4/CD8alphaalpha intraepithelial lymphocytes,
      and inflammation in the gut of vitamin D receptor KO mice.
AB  - Specific pathogen-free IL-10 KO mice failed to develop inflammatory bowel disease
      (IBD), whereas IL-10/vitamin D receptor (VDR) double KO mice developed
      fulminating IBD. WT CD4 T cells inhibited experimental IBD, while VDR KO CD4 T
      cells failed to suppress IBD. VDR KO mice had normal numbers and functions of
      regulatory T cells. The percentages of IL-17- and IFN-gamma-secreting T cells in
      the gut of mice reconstituted with WT and VDR KO CD4 T cells were also not
      different. Instead, there were twice as many CD8alphaalpha intraepithelial
      lymphocytes (IEL) in mice that were reconstituted with WT CD4 T cells than in
      mice reconstituted with VDR KO CD4 T cells. Furthermore, VDR KO mice had reduced
      numbers of CD8alphaalpha IEL, absent CD4/CD8alphaalpha populations, and as a
      result low IL-10 production in the IEL. The lack of CD8alphaalpha IEL was due in
      part to decreased CCR9 expression on T cells that resulted in the failure of the
      VDR KO T cells to home to the small intestine. We conclude that the VDR mediates
      T cell homing to the gut and as a result the VDR KO mouse has reduced numbers of
      CD8alphaalpha IEL with low levels of IL-10 leading to increased inflammatory
      response to the normally harmless commensal flora.

PMID- 19095794
TI  - Identification of gene 3' ends by automated EST cluster analysis.
AB  - The properties and biology of mRNA transcripts can be affected profoundly by the
      choice of alternative polyadenylation sites, making definition of the 3' ends of
      transcripts essential for understanding their regulation. Here we show that 22
      52% of sequences in commonly used human and murine "full-length" transcript
      databases may not currently end at bona fide polyadenylation sites. To identify
      probable transcript termini over the entire murine and human genomes, we analyzed
      the EST databases for positional clustering of EST ends. The analysis yielded
      58,282 murine- and 86,410 human-candidate polyadenylation sites, of which 75%
      mapped to 23,091 known murine transcripts and 22,891 known human transcripts. The
      murine dataset correctly predicted 97% of the 3' ends in a manually curated and
      experimentally supported benchmark transcript set. Of currently known genes, 15%
      had no associated prediction and 25% had only a single predicted termination
      site. The remaining genes had an average of 3-4 alternative polyadenylation sites
      predicted for each murine or human transcript, respectively. The results are made
      available in the form of tables and an interactive web site that can be mined for
      rapid assessment of the validity of 3' ends in existing collections, enumeration
      of potential alternative 3' polyadenylation sites of known transcripts, direct
      retrieval of terminal sequences for design of probes, and detection of
      polyadenylation sites not currently mapped to known genes.

PMID- 19095796
TI  - Direct role of structural dynamics in electron-lattice coupling of
      superconducting cuprates.
AB  - The mechanism of electron pairing in high-temperature superconductors is still
      the subject of intense debate. Here, we provide direct evidence of the role of
      structural dynamics, with selective atomic motions (buckling of copper-oxygen
      planes), in the anisotropic electron-lattice coupling. The transient structures
      were determined using time-resolved electron diffraction, following carrier
      excitation with polarized femtosecond heating pulses, and examined for different
      dopings and temperatures. The deformation amplitude reaches 0.5% of the c axis
      value of 30 A when the light polarization is in the direction of the copper
      oxygen bond, but its decay slows down at 45 degrees. These findings suggest a
      selective dynamical lattice involvement with the anisotropic electron-phonon
      coupling being on a time scale (1-3.5 ps depending on direction) of the same
      order of magnitude as that of the spin exchange of electron pairing in the high
      temperature superconducting phase.

PMID- 19095795
TI  - Preclinical evaluation of multiple species of PEGylated recombinant phenylalanine
      ammonia lyase for the treatment of phenylketonuria.
AB  - Phenylketonuria (PKU) is a metabolic disorder, in which loss of phenylalanine
      hydroxylase activity results in neurotoxic levels of phenylalanine. We used the
      Pah(enu2/enu2) PKU mouse model in short- and long-term studies of enzyme
      substitution therapy with PEGylated phenylalanine ammonia lyase (PEG-PAL
      conjugates) from 4 different species. The most therapeutically effective PAL (Av,
      Anabaena variabilis) species was one without the highest specific activity, but
      with the highest stability; indicating the importance of protein stability in the
      development of effective protein therapeutics. A PEG-Av-p.C503S/p.C565S-PAL
      effectively lowered phenylalanine levels in both vascular space and brain tissue
      over a >90 day trial period, resulting in reduced manifestations associated with
      PKU, including reversal of PKU-associated hypopigmentation and enhanced animal
      health. Phenylalanine reduction occurred in a dose- and loading-dependent manner,
      and PEGylation reduced the neutralizing immune response to the enzyme. Human
      clinical trials with PEG-Av-p.C503S/p.C565S-PAL as a treatment for PKU are
      underway.

PMID- 19095797
TI  - White spot syndrome virus protein ICP11: A histone-binding DNA mimic that
      disrupts nucleosome assembly.
AB  - White spot syndrome virus (WSSV) is a large ( approximately 300 kbp), double
      stranded DNA eukaryotic virus that has caused serious disease in crustaceans
      worldwide. ICP11 is the most highly expressed WSSV nonstructural gene/protein,
      which strongly suggests its importance in WSSV infection; but until now, its
      function has remained obscure. We show here that ICP11 acts as a DNA mimic. In
      crystal, ICP11 formed a polymer of dimers with 2 rows of negatively charged spots
      that approximated the duplex arrangement of the phosphate groups in DNA.
      Functionally, ICP11 prevented DNA from binding to histone proteins H2A, H2B, H3,
      and H2A.x, and in hemocytes from WSSV-infected shrimp, ICP11 colocalized with
      histone H3 and activated-H2A.x. These observations together suggest that ICP11
      might interfere with nucleosome assembly and prevent H2A.x from fulfilling its
      critical function of repairing DNA double strand breaks. Therefore, ICP11
      possesses a functionality that is unique among the handful of presently known DNA
      mimic proteins.

PMID- 19095798
TI  - Selectin catch-slip kinetics encode shear threshold adhesive behavior of rolling
      leukocytes.
AB  - The selectin family of leukocyte adhesion receptors is principally recognized for
      mediating transient rolling interactions during the inflammatory response. Recent
      studies using ultrasensitive force probes to characterize the force-lifetime
      relationship between P- and L-selectin and their endogenous ligands have
      underscored the ability of increasing levels of force to initially extend the
      lifetime of these complexes before disrupting bond integrity. This so-called
      "catch-slip" transition has provided an appealing explanation for shear threshold
      phenomena in which increasing levels of shear stress stabilize leukocyte rolling
      under flow. We recently incorporated catch-slip kinetics into a mechanical model
      for cell adhesion and corroborated this hypothesis for neutrophils adhering via L
      selectin. Here, using adhesive dynamics simulations, we demonstrate that
      biomembrane force probe measurements of various P- and L-selectin catch bonds
      faithfully predict differences in cell adhesion patterns that have been described
      extensively in vitro. Using phenomenological parameters to characterize the
      dominant features of molecular force spectra, we construct a generalized phase
      map that reveals that robust shear-threshold behavior is possible only when an
      applied force very efficiently stabilizes the bound receptor complex. This
      criteria explains why only a subset of selectin catch bonds exhibit a shear
      threshold and leads to a quantitative relationship that may be used to predict
      the magnitude of the shear threshold for families of catch-slip bonds directly
      from their force spectra. Collectively, our results extend the conceptual
      framework of adhesive dynamics as a means to translate complex single-molecule
      biophysics to macroscopic cell behavior.

PMID- 19095799
TI  - In vivo commitment and functional tissue regeneration using human embryonic stem
      cell-derived mesenchymal cells.
AB  - Development of clinically relevant regenerative medicine therapies using human
      embryonic stem cells (hESCs) requires production of a simple and readily
      expandable cell population that can be directed to form functional 3D tissue in
      an in vivo environment. We describe an efficient derivation method and
      characterization of mesenchymal stem cells (MSCs) from hESCs (hESCd-MSCs) that
      have multilineage differentiation potential and are capable of producing fat,
      cartilage, and bone in vitro. Furthermore, we highlight their in vivo survival
      and commitment to the chondrogenic lineage in a microenvironment comprising
      chondrocyte-secreted morphogenetic factors and hydrogels. Normal cartilage
      architecture was established in rat osteochondral defects after treatment with
      chondrogenically-committed hESCd-MSCs. In view of the limited available cell
      sources for tissue engineering applications, these embryonic-derived cells show
      significant potential in musculoskeletal tissue regeneration applications.

PMID- 19095800
TI  - The crystal structure of the second Z-DNA binding domain of human DAI (ZBP1) in
      complex with Z-DNA reveals an unusual binding mode to Z-DNA.
AB  - Mammalian DAI (DNA-dependent activator of IFN-regulatory factors), an activator
      of the innate immune response, senses cytosolic DNA by using 2 N-terminal Z-DNA
      binding domains (ZBDs) and a third putative DNA binding domain located next to
      the second ZBD. Compared with other previously known ZBDs, the second ZBD of
      human DAI (hZbeta(DAI)) shows significant variation in the sequence of the
      residues that are essential for DNA binding. In this article, the crystal
      structure of the hZbeta(DAI)/Z-DNA complex reveals that hZbeta(DAI) has a similar
      fold to that of other ZBDs, but adopts an unusual binding mode for recognition of
      Z-DNA. A residue in the first beta-strand rather than residues in the beta-loop
      contributes to DNA binding, and part of the (alpha3) recognition helix adopts a
      3(10) helix conformation. The role of each residue that makes contact with DNA
      was confirmed by mutational analysis. The 2 ZBDs of DAI can together bind to DNA
      and both are necessary for full B-to-Z conversion. It is possible that binding 2
      DAIs to 1 dsDNA brings about dimerization of DAI that might facilitate DNA
      mediated innate immune activation.

PMID- 19095801
TI  - Na+-mediated coupling between AMPA receptors and KNa channels shapes synaptic
      transmission.
AB  - Na(+)-activated K(+) (K(Na)) channels are expressed in neurons and are activated
      by Na(+) influx through voltage-dependent channels or ionotropic receptors, yet
      their function remains unclear. Here we show that K(Na) channels are associated
      with AMPA receptors and that their activation depresses synaptic responses.
      Synaptic activation of K(Na) channels by Na(+) transients via AMPA receptors
      shapes the decay of AMPA-mediated current as well as the amplitude of the
      synaptic potential. Thus, the coupling between K(Na) channels and AMPA receptors
      by synaptically induced Na(+) transients represents an inherent negative feedback
      mechanism that scales down the magnitude of excitatory synaptic responses.

PMID- 19095802
TI  - Neurogenesis and widespread forebrain migration of distinct GABAergic neurons
      from the postnatal subventricular zone.
AB  - Most forebrain GABAergic interneurons in rodents are born during embryonic
      development in the ganglionic eminences (GE) and migrate tangentially into the
      cortical plate. A subset, however, continues to be generated postnatally in the
      subventricular zone (SVZ). These interneurons populate the olfactory bulb (OB)
      reached via migration in the rostral migratory stream (RMS). Employing transgenic
      mice expressing EGFP in 5-HT(3)-positive neurons, we identified additional
      migratory pathways in the early postnatal brain. Time-lapse imaging experiments
      revealed massive migration of EGFP-positive cells from the SVZ into numerous
      forebrain regions, including cortex, striatum, and nucleus accumbens. The
      neuronal fate of the migratory EGFP-labeled cells was indicated by their
      doublecortin (DCX) expression. Birthdating experiments, by using 5-bromo-2'
      deoxyuridine (BrdU) and retrovirus-based experiments, provided evidence that
      migrating neuroblasts were born in the SVZ postnatally and developed a distinct
      GABAergic phenotype. Our results demonstrate that the SVZ is a reservoir of
      GABAergic interneurons not only for the OB, but also for other cortical and
      subcortical areas.

PMID- 19095803
TI  - SMD and NMD are competitive pathways that contribute to myogenesis: effects on
      PAX3 and myogenin mRNAs.
AB  - UPF1 functions in both Staufen 1 (STAU1)-mediated mRNA decay (SMD) and nonsense
      mediated mRNA decay (NMD), which we show here are competitive pathways. STAU1-
      and UPF2-binding sites within UPF1 overlap so that STAU1 and UPF2 binding to UPF1
      appear to be mutually exclusive. Furthermore, down-regulating the cellular
      abundance of STAU1, which inhibits SMD, increases the efficiency of NMD, whereas
      down-regulating the cellular abundance of UPF2, which inhibits NMD, increases the
      efficiency of SMD. Competition under physiological conditions is exemplified
      during the differentiation of C2C12 myoblasts to myotubes: The efficiency of SMD
      increases and the efficiency of NMD decreases, consistent with our finding that
      more STAU1 but less UPF2 bind UPF1 in myotubes compared with myoblasts. Moreover,
      an increase in the cellular level of UPF3X during myogenesis results in an
      increase in the efficiency of an alternative NMD pathway that, unlike classical
      NMD, is largely insensitive to UPF2 down-regulation. We discuss the remarkable
      balance between SMD and the two types of NMD in view of data indicating that PAX3
      mRNA is an SMD target whose decay promotes myogenesis whereas myogenin mRNA is a
      classical NMD target encoding a protein required for myogenesis.

PMID- 19095804
TI  - MAPK target networks in Arabidopsis thaliana revealed using functional protein
      microarrays.
AB  - Signaling through mitogen-activated protein kinases (MPKs) cascades is a complex
      and fundamental process in eukaryotes, requiring MPK-activating kinases (MKKs)
      and MKK-activating kinases (MKKKs). However, to date only a limited number of MKK
      MPK interactions and MPK phosphorylation substrates have been revealed. We
      determined which Arabidopsis thaliana MKKs preferentially activate 10 different
      MPKs in vivo and used the activated MPKs to probe high-density protein
      microarrays to determine their phosphorylation targets. Our analyses revealed
      known and novel signaling modules encompassing 570 MPK phosphorylation
      substrates; these substrates were enriched in transcription factors involved in
      the regulation of development, defense, and stress responses. Selected MPK
      substrates were validated by in planta reconstitution experiments. A subset of
      activated and wild-type MKKs induced cell death, indicating a possible role for
      these MKKs in the regulation of cell death. Interestingly, MKK7- and MKK9-induced
      death requires Sgt1, a known regulator of cell death induced during plant innate
      immunity. Our predicted MKK-MPK phosphorylation network constitutes a valuable
      resource to understand the function and specificity of MPK signaling systems.

PMID- 19095805
TI  - Electrical stimulation using kilohertz-frequency alternating current.
AB  - Transcutaneous electrical stimulation using kilohertz-frequency alternating
      current (AC) became popular in the 1950s with the introduction of "interferential
      currents," promoted as a means of producing depth-efficient stimulation of nerve
      and muscle. Later, "Russian current" was adopted as a means of muscle
      strengthening. This article reviews some clinically relevant, laboratory-based
      studies that offer an insight into the mechanism of action of kilohertz-frequency
      AC. It provides some answers to the question: "What are the optimal stimulus
      parameters for eliciting forceful, yet comfortable, electrically induced muscle
      contractions?" It is concluded that the stimulation parameters commonly used
      clinically (Russian and interferential currents) are suboptimal for achieving
      their stated goals and that greater benefit would be obtained using short
      duration (2-4 millisecond), rectangular bursts of kilohertz-frequency AC with a
      frequency chosen to maximize the desired outcome.

PMID- 19095807
TI  - An abdominal muscular fold mimicking tumour.
AB  - Mass-like lesions and anatomical variations sometimes create challenges for
      diagnosis in both clinical and radiology practice. We present a "pseudomass"
      originating from the right abdominal wall in a 75-year-old patient with invasive
      ductal carcinoma of the breast. Age-related structural changes in the abdominal
      wall, as well as anatomical variations, should be kept in mind in order to
      establish the correct radiological diagnosis and to avoid unnecessary procedures.

PMID- 19095808
TI  - Acute necrotizing pancreatitis following inadvertent extensive splenic artery
      embolisation for trauma.
AB  - We present a case of splenic artery embolisation (SAE) after traumatic splenic
      injury that was complicated by acute necrotizing pancreatitis, caused by
      inadvertently extensive embolisation of the splenic artery. Although SAE is
      increasingly used for splenic preservation in trauma, there is insufficient
      knowledge on its efficacy and pitfalls. This report aims to draw attention to a
      rare but potentially serious complication of SAE.

PMID- 19095806
TI  - Clinical prediction rules for physical therapy interventions: a systematic
      review.
AB  - BACKGROUND AND PURPOSE: Clinical prediction rules (CPRs) involving physical
      therapy interventions have been published recently. The quality of the studies
      used to develop the CPRs was not previously considered, a fact that has potential
      implications for clinical applications and future research. The purpose of this
      systematic review was to determine the quality of published CPRs developed for
      physical therapy interventions. METHODS: Relevant databases were searched up to
      June 2008. Studies were included in this review if the explicit purpose was to
      develop a CPR for conditions commonly treated by physical therapists. Validated
      CPRs were excluded from this review. Study quality was independently determined
      by 3 reviewers using standard 18-item criteria for assessing the methodological
      quality of prognostic studies. Percentage of agreement was calculated for each
      criterion, and the intraclass correlation coefficient (ICC) was determined for
      overall quality scores. RESULTS: Ten studies met the inclusion criteria and were
      included in this review. Percentage of agreement for individual criteria ranged
      from 90% to 100%, and the ICC for the overall quality score was .73 (95%
      confidence interval=.27-.92). Criteria commonly not met were adequate description
      of inclusion or exclusion criteria, inclusion of an inception cohort, adequate
      follow-up, masked assessments, sufficient sample sizes, and assessments of
      potential psychosocial factors. Quality scores for individual studies ranged from
      48.2% to 74.0%. DISCUSSION AND CONCLUSION: Validation studies are rarely reported
      in the literature; therefore, CPRs derived from high-quality studies may have the
      best potential for use in clinical settings. Investigators planning future
      studies of physical therapy CPRs should consider including inception cohorts,
      using longer follow-up times, performing masked assessments, recruiting larger
      sample sizes, and incorporating psychological and psychosocial assessments.

PMID- 19095809
TI  - Primary malignant lymphoma of the gallbladder: a case report and literature
      review.
AB  - Primary malignant lymphoma of the gallbladder is extremely rare and the
      associated radiological findings are not well described in the literature. We
      report a case of malignant lymphoma in the gallbladder wall of a 78-year-old
      woman. Pre-operative CT and MRI showed homogeneous submucosal thickening of the
      gallbladder wall with a preserved mucosal surface. These unique radiological
      findings may be useful for diagnosing malignant lymphoma of the gallbladder.

PMID- 19095810
TI  - Clear cell adenocarcinoma of the uterine cervix arising from a background of
      cervical endometriosis.
AB  - The radiological findings of cervical clear cell adenocarcinoma (CCA) have not
      been described previously. Here, we present MR findings of this neoplasm that
      included mixed solid and cystic components with eccentric solid components. These
      are similar to the MR features of ovarian CCA. Endometriosis was also noted in
      the uterine cervix. Coexistence of CCA and endometriosis at the cervix suggests
      that the pathogenesis may be similar to that of ovarian CCA.

PMID- 19095811
TI  - False-positive positron emission tomography appearance with 18F
      fluorodeoxyglucose after definitive radiotherapy for cancer of the mobile tongue.
AB  - (18)F-fluorodeoxyglucose-positron emission tomography (FDG-PET) is an effective
      tool for evaluating the results of radiotherapy. However, some false-positive
      appearances caused by physiological or pathological accumulation are reported. We
      report on three patients who showed a high accumulation of FDG in the lingual
      muscles but had no recurrent tumour after definitive radiotherapy for the mobile
      tongue. All patients had squamous cell carcinoma of the tongue and received
      interstitial radiotherapy with small sources. High uptake was seen in the lingual
      muscles without recurrence or inflammation, based on physical and MR
      examinations. This false-positive appearance is thought to relate to ill-balanced
      high activity of the lingual muscles after definitive radiotherapy.

PMID- 19095812
TI  - Coronary myocardial bridging in Noonan syndrome: definitive diagnosis with high
      resolution CT.
AB  - Noonan syndrome is an autosomal dominant disorder reported at an incidence of 1
      in 1000-2500 live-born patients. Pulmonary stenosis with a dysplastic pulmonary
      valve and hypertrophic cardiomyopathy are often associated with this syndrome. We
      report on a 9-year-old patient affected by Noonan syndrome with left ventricle
      hypertrophy, in whom a sudden clinical presentation of chest pain after effort
      led to the clinical suspicion of associated coronary myocardial bridging, which
      was confirmed by high-resolution CT. We also review the literature on this topic.

PMID- 19095813
TI  - Do screen-detected lobular and ductal carcinoma present with different
      mammographic features?
AB  - The aim of this study is to investigate any difference in the shape and location
      of infiltrating lobular carcinoma (ILC) with respect to the parenchymal density
      between the cranio-caudal (CC) and medio-lateral oblique (MLO) mammographic
      views. Six film-readers independently re-read 59 ILC mammograms and a matched
      sample of 59 infiltrating ductal carcinoma (IDC) mammograms from one 3-year
      screening round to quantify lesion characteristics. There is fair to moderate
      reader agreement for parenchymal pattern, lesion shape and location (kappa = 0.41
      0.60). Both ILC (33/60, 55%) and IDC (22/65, 37%) appear as a spiculate mass more
      often on the CC view than on the MLO view. 41% (25/60) of the ILC spiculate
      masses become architectural distortions or asymmetric densities on the MLO view.
      No more ILC lesions (4/60, 7%) are seen in dense breasts than IDC (5/65, 8%), but
      ILC is mainly associated with (58/60, 97%), and rarely isolated from (2/60, 3%),
      the main glandular density. The appearance of ILC is significantly different
      between the MLO and CC views (paired Wilcoxon test: z = -17.059; significance
      level <or=0.0005). IDC appearance is not significantly different between these
      two views (z = -1.244; significance level 0.213). In conclusion, the CC view is
      optimum for distinctly visualizing ILC as a spiculate mass, as it appears as a
      more subtle distortion or asymmetry on the MLO view. ILC is not often isolated
      from the main glandular density and so optimizing visualization of this area of
      the breast is key to perception.

PMID- 19095814
TI  - Advanced pancreatic cancer: the use of the apparent diffusion coefficient to
      predict response to chemotherapy.
AB  - The purpose of this study was to determine if the apparent diffusion coefficient
      (ADC) on diffusion-weighted MRI could predict the response of patients with
      advanced pancreatic cancer to chemotherapy. Diffusion-weighted MRI was performed
      in 63 consecutive patients with advanced pancreatic cancer who were subsequently
      treated with chemotherapy. The ADC values of the primary tumour with a middle b
      value (400 s mm(-2)) and a high b-value (1000 s mm(-2)) were determined; cystic
      or necrotic components were avoided. The patients were classified into two
      groups: (i) those with progressive disease and (ii) those who were stable 3
      months and 6 months after initial treatment. The groups were compared with
      respect to the ADC and clinical factors, including gender, age, Union
      International Contre le Cancer (UICC ) stage, initial tumour size and
      chemotherapy agents used. Local tumour progression rates were evaluated using the
      Kaplan-Meier method. The middle b-value ADC of the pancreatic cancers ranged from
      0.93-2.42 x10(-3) mm(2) s(-1) (mean, 1.50 x10(-3) mm(2) s(-1)), and the high b
      value ADC ranged from 0.72-1.88 x10(-3) mm(2) s(-1) (mean, 1.20 x10(-3) mm(2) s(
      1)). The high b-value ADC was significantly different between the progressive and
      stable groups at 3 months' and 6 months' follow-up (p = 0.03 and p = 0.04,
      respectively). The rate of tumour progression was significantly higher in those
      with a lower high b-value ADC than in those with a higher b-value ADC (median
      progression time, 140 days vs 182 days; p = 0.01). In conclusion, a lower high b
      value ADC in patients with advanced pancreatic cancer may be predictive of early
      progression in chemotherapy-treated patients.

PMID- 19095816
TI  - Optimizing the tube potential for lumbar spine radiography with a flat-panel
      digital detector.
AB  - The purpose of this study was to find the optimal settings for lumbar spine
      radiography with a flat-panel detector. A CDRAD contrast-detail phantom was
      imaged at various tube potentials, system speeds and filtration settings.
      Factorial experiments yielded a range of optimized exposure settings, which were
      submitted to visual grading analysis with images of an Alderson phantom. The
      first optimized settings involved a system speed increase from 400 to 800. For
      anteroposterior projection, the optimal tube potential was reduced from the
      default of 77 kV to 60 kV to give the best image quality without increasing the
      effective dose, or to 66 kV to give the lowest dose without reducing image
      quality. For lateral projection, the tube potential was similarly reduced from
      the default of 90 kV to 70 kV or 77 kV. Visual grading analysis confirmed the
      results, with significantly better image quality when optimizing for image
      quality. The study thus shows that the tube potential can be reduced as long as
      the system speed is increased simultaneously. This leads to a lower effective
      dose and/or increased image quality depending on the settings chosen. The
      factorial experiments provided a powerful way to evaluate several parameters
      concomitantly.

PMID- 19095815
TI  - Sentinel lymph node biopsy using dynamic lymphoscintigraphy combined with
      ultrasound-guided fine needle aspiration in penile carcinoma.
AB  - The purpose of this study was to assess the utility of sentinel lymph node
      lymphoscintigraphy (SLNL) and ultrasound-guided fine needle aspiration cytology
      (FNAC) in patients with penile carcinoma. A prospective study was undertaken of
      64 patients with stage T1 (or greater) clinically N0 squamous cell carcinoma of
      the penis. Patients underwent SLNL and bilateral groin ultrasonography with or
      without FNAC. Following intradermal blue dye, patients underwent unilateral or
      bilateral sentinel lymph node excision biopsy (SNB). 17 patients had sentinel
      nodes that contained metastases (21 nodal basins). Lymphatic drainage was
      demonstrated in all patients by lymphoscintigraphy. Bilateral drainage was seen
      in 57/64 patients. 61/64 patients had ultrasonography of the inguinal basins on
      the same day as FNAC of 38 basins. FNAC showed malignancy in eight basins. FNAC
      was negative in six basins, which were subsequently shown to be positive
      following SNB. 82 inguinal basins did not warrant FNAC by ultrasound criteria, of
      which 5 contained metastases at SNB. The sensitivity and specificity of
      ultrasonography was 74% and 77%, respectively. The positive and negative
      predictive values were 37% and 94%, respectively. Two patients had a negative
      initial SNB; however, ultrasonography identified a metastatic node and re
      evaluation of the sentinel node confirmed micro-metastases. There has been no
      evidence of recurrence in any patients with negative SNB (during 6-28 months'
      follow-up). In conclusion, when investigating clinically stage N0 penile cancer,
      the combination of SNB and groin ultrasonography, with or without FNAC,
      identifies accurately those with occult nodal metastases. Ultrasonography alone
      is not adequate as a staging technique, and SNB alone might miss between 5% and
      10% of metastases.

PMID- 19095817
TI  - Interobserver variability in the measurement of abdominal aortic calcification
      using unenhanced CT.
AB  - Arterial calcification is well recognized as being associated with an increased
      risk of adverse cardiovascular events. Numerous methods for its quantification
      have been published, with no consensus on the technique used. In order to assess
      the reproducibility of a novel technique for quantifying aortic calcification, we
      measured the interobserver variability between two observers analysing the
      abdominal aortas of 34 volunteer patients. Using non-contrast abdominal CT images
      together with commercial imaging software, the quantity of calcium in a pre
      determined section of aorta was calculated for each patient, and the difference
      in values obtained between the two observers compared using a Bland-Altman plot.
      Minimal interobserver variability was observed, with a significant difference in
      results occurring for only two patients. This protocol therefore represents a
      reliable technique that may be applied as a future standard in order to
      facilitate comparison between studies.

PMID- 19095818
TI  - Case of the month. Flank swelling following abdominal trauma: an easily
      overlooked injury.

PMID- 19095819
TI  - CT diagnosis of pulmonary artery dissection--potential pitfall of multidetector
      CT.

PMID- 19095820
TI  - Radiofrequency ablation of renal cell carcinoma with pathological correlation.

PMID- 19095821
TI  - Changes in Anesthesia & Analgesia for 2009.

PMID- 19095822
TI  - Targeting beta2-adrenoceptors for neuroprotection after cerebral ischemia: is
      inhibition or stimulation best?

PMID- 19095823
TI  - Lake Wobegon for anesthesia...where everyone is above average except those who
      aren't: variability in the management of simulated intraoperative critical
      incidents.

PMID- 19095824
TI  - The intraoperative quantification of aortic stenosis.

PMID- 19095825
TI  - The feasibility of epicardial echocardiography for measuring aortic valve area by
      the continuity equation.
AB  - BACKGROUND: Measuring the aortic valve area (AVA) remains an important component
      of a comprehensive intraoperative echocardiographic examination in patients
      undergoing aortic valve surgery. Epicardial echocardiography (EE) represents an
      accessible alternative to transesophageal echocardiography (TEE), however, its
      agreement and correlation with other imaging modalities for measuring AVA has not
      been systematically validated. METHODS: EE was used in 85 patients undergoing
      cardiac surgery to measure AVA (AVA-EE) using the continuity equation. AVA-EE was
      compared to measurements obtained by intraoperative transesophageal
      echocardiography (AVA-TEE) in the same population. In a subset of patients, AVA
      EE was also compared to AVA measurements from either preoperative transthoracic
      echocardiography (AVA-TTE) (n = 65) or cardiac catheterization (AVA-Cath) (n =
      35) that were acquired within 4 wk before the date of surgery. RESULTS: Adequate
      trans-AV Doppler recordings were obtained in 94% of patients for AVA-TEE and 100%
      of patients for AVA-EE. EE measurements of AVA showed close agreement with TEE
      measurements (mean difference [bias] +/- 95% CI = -0.09 cm(2) +/- 0.18 cm(2),
      r(2) = 0.83, P < 0.0001). AVA-EE also agreed well with AVA-Cath (mean difference
      +/- 95% CI = -0.03 cm(2) +/- 0.12 cm(2), r(2) = 0.87, P < 0.0001) and AVA-TTE
      (mean difference +/- 95% CI = -0.06 cm(2) +/- 0.22 cm(2), r(2) = 0.81, P <
      0.0001). CONCLUSIONS: EE measurements of AVA by the continuity equation show high
      agreement and closely correlate with established techniques of AVA assessment.

PMID- 19095826
TI  - Intrathecal morphine preconditioning induces cardioprotection via activation of
      delta, kappa, and mu opioid receptors in rats.
AB  - BACKGROUND: Small doses of intrathecal morphine provide cardioprotection similar
      to that conferred by IV morphine. However, the extent of intrathecal morphine
      preconditioning (IT-MPC) relative to that resulting from ischemic preconditioning
      (IPC) is unknown. Further, it is uncertain whether IT-MPC is mediated by opioid
      receptor dependent pathways. In this study, we compared the extent of
      cardioprotection conferred by IT-MPC with IPC and investigated the role of opioid
      receptors in this effect. METHODS: Eighty anesthetized, open-chest, male Sprague
      Dawley rats were assigned to 1 of 13 groups (n = 6-7) after successful
      intrathecal catheter placement. Rats in the IPC group were subjected to three 5
      min cycles of myocardial ischemia (induced by occlusion of the left main coronary
      artery) interspersed with 5 min of reperfusion. After IPC, myocardial ischemia
      and reperfusion injury was induced by 30 min of left main coronary artery
      occlusion followed by 2 h of reperfusion. In the IT-MPC groups, the rats were
      given 3 consecutive 5 min intrathecal morphine infusions (0.03, 0.3, 3.0, or 30.0
      microg/kg, respectively) interspersed with 5 min infusion-free periods, before
      myocardial ischemia reperfusion injury. In 2 other groups either 300microg/kg of
      IV morphine or 10 microL of intrathecal normal saline were given. The selective
      delta, kappa, and mu opioid receptor antagonists naltrindole, nor
      binaltorphimine, and D-Phe-Cys-Tyr-D-Trp-Orn-Thr-Pen-Thr-NH2 (CTOP),
      respectively, were given to groups of animals receiving IT-MPC to evaluate the
      relative role of the specific opioid receptor subtypes in IT-MPC preconditioning.
      Myocardial infarct size (IS), as a percentage of the area at risk (AAR), was
      determined by 2,3,5-triphenyltetrazolium staining. RESULTS: Intrathecal morphine
      0.3 to 30 microg/kg reduced myocardial IS compared with intrathecal normal saline
      control animals. The IS/AAR were 33% +/- 10% (0.3 microg/kg), 29% +/- 10% (3
      microg/kg) and 29% +/- 16% (30 mug/kg), versus 53% +/- 8% for the control group
      (P < 0.01). The reduction in IS/AAR with IT-MPC was similar to that produced by
      IV morphine (33% +/- 6%, P = 0.84) and IPC (22% +/- 4%, P = 0.41). Myocardial
      preconditioning due to IT-MPC was attenuated by co-administration of any one of
      the opioid receptor antagonists (IT-MPC + naltrindole 50% +/- 9%, IT-MPC + nor
      binaltorphimine 43% +/- 6%, IT-MPC + CTOP 53% +/- 9%, P = 0.14). CONCLUSIONS: IT
      MPC produced comparable cardioprotection to myocardial IPC and IV morphine.
      Myocardial preconditioning from intrathecal morphine seems to involve delta,
      kappa, and mu opioid receptors.

PMID- 19095827
TI  - Rapidly degradable hydroxyethyl starch solutions impair blood coagulation after
      cardiac surgery: a prospective randomized trial.
AB  - BACKGROUND: There is continuing concern about the effect of hydroxyethyl starch
      (HES) solutions on blood coagulation. Rapidly degradable HES solutions with more
      favorable effects on clot strength have therefore been developed. Because the
      risk of bleeding is increased after cardiopulmonary bypass, we examined whether
      these types of HES solutions could be administered after cardiac surgery without
      an alteration of coagulation. METHODS: Two new rapidly degradable HES solutions
      were compared with human albumin in 45 patients scheduled for elective primary
      cardiac surgery. After admission to the cardiac surgical intensive care unit, the
      patients were allocated in random order to receive either 15 mL/kg of HES
      solution with low molecular weight and low molar substitution (either 6%
      HES200/0.5 or 6% HES130/0.4) or 4% human albumin solution as a short-time (70-240
      min) infusion. RESULTS: Clot formation time was prolonged and maximum clot
      firmness was decreased in thromboelastometry tracings after infusion of both HES
      solutions. This impairment in thromboelastometry tracings partly recovered (using
      InTEM and ExTEM coagulation activators) at 2 h after the completion of the study
      infusion. Platelet contribution to maximum clot firmness remained unaffected in
      all of the study groups. HES did not induce fibrinolysis. No changes in
      thromboelastometry tracings were observed after human albumin infusion. Chest
      tube drainage was comparable in the study groups. CONCLUSIONS: We conclude that a
      short-time infusion of rapidly degradable HES solutions after cardiac surgery
      produces impairment in fibrin formation and clot strength in thromboelastometry
      tracings. In this clinical setting, human albumin does not impair hemostasis.

PMID- 19095828
TI  - PRO: Intraoperative Doppler tissue imaging is a valuable addition to cardiac
      anesthesiologists' armamentarium.

PMID- 19095829
TI  - CON: Intraoperative Doppler tissue imaging is a valuable addition to cardiac
      anesthesiologists' armamentarium.

PMID- 19095830
TI  - Intraoperative Doppler tissue imaging is a valuable addition to cardiac
      anesthesiologists' armamentarium: a core review.
AB  - Endocardial motion and surface/volume changes during the cardiac cycle are
      echocardiographic methods for regional (analysis of wall motion) and global
      (fractional area change, stroke volume, and ejection fraction) evaluation of
      cardiac function. These conventional methods can be subjective, and/or time
      consuming and, depending upon circumstances, may divert the anesthesiologist's
      attention from intraoperative activities. Doppler tissue imaging (DTI) is a novel
      echocardiographic technique, which displays and measures systolic and diastolic
      velocity from a myocardial region. DTI is simple to perform and independent of
      adequate endocardial imaging. The numeric information (velocity or time
      intervals) is easily obtained and measured. Assessment of systolic and diastolic
      function on regional (detection of ischemia) as well as global level (ejection
      fraction, grading of diastolic dysfunction) and evaluation of filling pressure
      can be derived from DTI signals and used by any practicing cardiac
      anesthesiologist. This review describes the principles, imaging modalities, and
      clinical applications of DTI.

PMID- 19095831
TI  - Echocardiographic evaluation during pulmonary artery stenting.

PMID- 19095832
TI  - Thrombus or bilobar left atrial appendage? Diagnosis by real-time three
      dimensional transesophageal echocardiography.

PMID- 19095833
TI  - Left ventricular assist device outflow cannula obstruction by the rare
      environmental fungus Myceliophthora thermophila.
AB  - Left ventricular assist devices are used to provide mechanical circulatory
      support during end-stage heart failure either as a destination therapy or as a
      bridge to heart transplantation. Perioperative transesophageal echocardiography
      is becoming an invaluable tool to investigate device function during implantation
      and in case of mechanical malfunction. Most malfunctions are due to inflow graft
      occlusion, or device malfunction, while outflow graft dysfunction is rare. Here,
      we present a case of severe outflow conduit obstruction by a rare environmental
      fungus, Myceliophthora thermophila. After replacement of the infected device and
      intensive antifungal treatment, heart transplantation was performed 2 yr later.

PMID- 19095834
TI  - Routine preoperative coagulation screening detects a rare bleeding disorder.
AB  - Factor X deficiency is a rare hereditary coagulation disorder. We report a case
      of congenital factor X deficiency diagnosed preoperatively in an 8-yr-old female
      child scheduled to undergo corrective surgery for congenital thoracolumbar
      kyphoscoliosis. Her preoperative coagulation profile revealed prolonged
      prothrombin time and activated partial thromboplastin time values. Further
      evaluation showed functional activity of factor X was <8% of the normal activity
      and was corrected to 10%-40% of the normal activity with fresh frozen plasma. IV
      tranexamic acid was also administered to reduce intraoperative blood loss. There
      were no postoperative bleeding complications. This case emphasizes the need for
      routine preoperative coagulation screening, at least for major surgical
      procedures.

PMID- 19095835
TI  - Incidence and risk factors for perioperative hyperglycemia in children with
      traumatic brain injury.
AB  - BACKGROUND: Hyperglycemia after traumatic brain injury (TBI) is associated with
      poor outcome. In this study, we examined the incidence and risk factors for
      perioperative hyperglycemia in children with TBI. METHODS: A retrospective cohort
      study of children <or=13 yr who underwent urgent or emergent craniotomy for TBI
      at Harborview Medical Center (level I Adult and Pediatric Trauma Center) between
      1994 and 2004 was performed. Preoperative (emergency department to general
      anesthesia start), intraoperative (during general anesthesia), and immediate
      postoperative (first 24 h after surgery) glucose values for each patient were
      retrieved. The incidence of hyperglycemia (glucose >or=200 mg/dL) and
      hypoglycemia (glucose <60 mg/dL) was determined. Persistent hyperglycemia was
      defined as hyperglycemia during any 2/3 (preoperative, intraoperative, and
      immediate postoperative) study periods, whereas transient hyperglycemia was
      defined as hyperglycemia during any one study period. Multivariate logistic
      regression analysis was used to determine the independent predictors of
      perioperative hyperglycemia. Data are presented as adjusted odds ratio (AOR) (95%
      CI) and P < 0.05 reflects significance. RESULTS: At least one serum glucose value
      was recorded during each study period: preoperative (86 [82%]), intraoperative
      (94 [89%]), and postoperative (101 [97%]). Sixty-four percent of children had
      less than one glucose recorded per anesthetic hour. Forty-seven (45%) children
      had hyperglycemia during at least one study period. Transient hyperglycemia
      occurred in 29 (28%) and persistent hyperglycemia occurred in 18 (17%) children.
      Independent predictors of perioperative hyperglycemia were age <4 yr (AOR [95%
      CI]; 3.5 [1.2-10.6]), Glasgow Coma Scale <or=8 (AOR 95% CI; 7.2 [2.4-21.5]) and
      the presence of multiple lesions including subdural hematoma (AOR 95% CI; 34.7
      [2.3-525.5]). Six children were treated with insulin, and two children had
      hypoglycemia, unrelated to insulin treatment. CONCLUSIONS: Perioperative
      hyperglycemia was common and intraoperative hypoglycemia was not rare, but more
      frequent intraoperative glucose sampling may be needed to better determine the
      incidence of hypo and hyperglycemia during the perioperative period. Age <4 yr,
      severe TBI and the presence of multiple lesions, including subdural hematoma,
      were risk factors for perioperative hyperglycemia.

PMID- 19095836
TI  - The effects of neonatal isoflurane exposure in mice on brain cell viability,
      adult behavior, learning, and memory.
AB  - BACKGROUND: Volatile anesthetics, such as isoflurane, are widely used in infants
      and neonates. Neurodegeneration and neurocognitive impairment after exposure to
      isoflurane, midazolam, and nitrous oxide in neonatal rats have raised concerns
      regarding the safety of pediatric anesthesia. In neonatal mice, prolonged
      isoflurane exposure triggers hypoglycemia, which could be responsible for the
      neurocognitive impairment. We examined the effects of neonatal isoflurane
      exposure and blood glucose on brain cell viability, spontaneous locomotor
      activity, as well as spatial learning and memory in mice. METHODS: Seven-day-old
      mice were randomly assigned to 6 h of 1.5% isoflurane with or without injections
      of dextrose or normal saline, or to 6 h of room air without injections (no
      anesthesia). Arterial blood gases and glucose were measured. After 2 h, 18 h, or
      11 wk postexposure, cellular viability was assessed in brain sections stained
      with Fluoro-Jade B, caspase 3, or NeuN. Nine weeks postexposure, spontaneous
      locomotor activity was assessed, and spatial learning and memory were evaluated
      in the Morris water maze using hidden and reduced platform trials. RESULTS:
      Apoptotic cellular degeneration increased in several brain regions early after
      isoflurane exposure, compared with no anesthesia. Despite neonatal cell loss,
      however, adult neuronal density was unaltered in two brain regions significantly
      affected by the neonatal degeneration. In adulthood, spontaneous locomotor
      activity and spatial learning and memory performance were similar in all groups,
      regardless of neonatal isoflurane exposure. Neonatal isoflurane exposure led to
      an 18% mortality, and transiently increased Paco(2), lactate, and base deficit,
      and decreased blood glucose levels. However, hypoglycemia did not seem
      responsible for the neurodegeneration, as dextrose supplementation failed to
      prevent neuronal loss. CONCLUSIONS: Prolonged isoflurane exposure in neonatal
      mice led to increased immediate brain cell degeneration, however, no significant
      reductions in adult neuronal density or deficits in spontaneous locomotion,
      spatial learning, or memory function were observed.

PMID- 19095837
TI  - Subspecialty impact factors: the contribution of pediatric anesthesia and pain
      articles.
AB  - BACKGROUND: The Science Citation Index "Journal Impact Factor" (JIF) is widely
      used to assess journal quality and prestige. The JIFs for the specialty
      anesthesia are reported annually, however, the impact factors (IFs) for
      subspecialties in those journals have not been reported. Therefore, we compared
      the IFs of pediatric anesthesia (Ped IFs) and pain (Pain IFs) articles from four
      anesthesia journals for two epochs. METHODS: An article-by-article manual search
      for "source" pediatric anesthesia and pain articles published in 1998, 1999,
      2003, and 2004 in Anesthesiology, Anesthesia & Analgesia, British Journal of
      Anaesthesia, and Canadian Journal of Anesthesia was performed. The citations for
      each of these articles in each of the years were surveyed in the ISI Web of
      Science database. Ped IFs and Pain IFs for the 2000 and 2005 epochs were
      calculated and compared with the JIF from which they were derived and to those of
      the journal, Pediatric Anesthesia. RESULTS: Ped IFs for the four journals in 2005
      exceeded those in 2000, whereas the Pain IFs were unchanged. For both the Ped IFs
      and the Pain IFs, there was a significant effect of the journal. The Pain IFs
      were 70% greater than the Ped IFs. CONCLUSIONS: Ped IFs were consistently less
      than the JIFs in which they were published and the Pain IFs, except for the
      British Journal of Anaesthesia 2005 in the latter case. The numbers of citations
      of pediatric anesthesia articles were greater in journals with greater IFs. The
      implications of subspecialty IFs warrant further consideration.

PMID- 19095838
TI  - The influence of head and neck position on the oropharyngeal leak pressure and
      cuff position of three supraglottic airway devices.
AB  - BACKGROUND: With supraglottic airway devices, such as the laryngeal tube suction
      (LTS), ProSeal laryngeal mask airway (PLMA) and Cobra perilaryngeal airway
      (CobraPLA), oropharyngeal leak pressure or cuff position may vary according to
      changes in the position of the head and neck. We evaluated oropharyngeal leak
      pressure and cuff pressure of the PLMA, LTS, and CobraPLA in different head and
      neck positions. METHODS: One-hundred-thirty-nine patients (aged 18-70 yr)
      scheduled for minor surgical procedures were randomly allocated to one of the
      supraglottic airway devices. Oropharyngeal leak pressure and cuff pressure were
      evaluated in four head and neck positions: neutral, 45 degrees of flexion, 45
      degrees of extension, and 45 degrees of right rotation. Adverse events (i.e.,
      difficulty in ventilation or gastric insufflation) were assessed during the
      study. RESULTS: Leak pressures of the PLMA were lowest in the extension (18.5 vs
      23.9 and 26.8 cm H(2)O of LTS and CobraPLA, respectively; P < 0.001) and in the
      rotation position (25.0 vs 29.4 and 28.5 cm H(2)O of LTS and CobraPLA,
      respectively; P < 0.005). With the CobraPLA, gastric insufflations occurred
      before the oropharyngeal leak in 37 of 45 patients. There were ventilatory
      difficulties in seven patients with LTS after neck flexion, which required
      tracheal intubation. CONCLUSIONS: The PLMA showed significantly lower
      oropharyngeal leak pressures than did the LTS or CobraPLA in the neck extension
      and rotation positions. Caution is warranted when changing the position of the
      head and neck when using the Cobra-PLA or LTS as gastric insufflation or
      ventilatory difficulty may occur.

PMID- 19095839
TI  - Alveolar recruitment and arterial desflurane concentration during bariatric
      surgery.
AB  - BACKGROUND: We investigated whether reversal of intraoperative atelectasis with
      the lung recruitment maneuver (RM) affects desflurane arterial concentrations
      during bariatric surgery. METHODS: After anesthetic induction and maintenance
      with propofol, patients were randomized to receive alveolar RM at intervals (RM
      group) or not (controls). Desflurane 6% was initiated, and rate of increase of
      alveolar desflurane concentration (ratio of end-expiratory to inspiratory
      concentrations, F(A)/F(I)) and desflurane blood concentrations were measured in
      both groups. Blood and end-tidal desflurane concentrations were also measured
      after the discontinuation of anesthesia. RESULTS: The RM group had higher
      intraoperative Pao(2)/Fio(2) compared with the control group (both, P < 0.001).
      During induction, the rate of increase in blood desflurane concentrations was
      rapid in both groups. At comparable mechanical ventilation settings, median times
      to achieve 0.5 mM (approximately 3%) were 2.1 and 1.59 min (P = 0.09) in the
      control and RM group, respectively. The times to achieve 0.7 mM (approximately
      4.2%) desflurane were 15.9 and 9.3 min in the control and RM group, respectively
      (P = 0.08). Desflurane blood concentrations tended to be higher during the first
      30 min after induction in the RM group (P = 0.066). During maintenance or
      emergence, the blood desflurane concentrations were not different between control
      and RM groups. Consequently, the time to eye opening did not differ between
      groups. CONCLUSION: Although the RM during bariatric surgery represents an
      effective method for improving intraoperative oxygenation, it does not
      significantly affect the desflurane blood concentrations during anesthesia or its
      elimination during emergence.

PMID- 19095841
TI  - Nicotinic receptors partly mediate brainstem autonomic dysfunction evoked by the
      inhaled anesthetic isoflurane.
AB  - BACKGROUND: Isoflurane is one of the most commonly used volatile anesthetics, yet
      the cardiorespiratory depression that occurs with its use remains poorly
      understood. In this study, the author examined isoflurane modulation of
      postsynaptic gamma-aminobutyric acid (GABA) receptors in parasympathetic cardiac
      vagal neurons (CVNs) and alterations of GABAergic function by targeting nicotinic
      acetylcholine receptors on GABAergic presynaptic terminals. METHODS: Rhythmic
      inspiratory-related activity was recorded from the hypoglossal rootlet of 800
      microm medullary sections. CVNs were identified by retrograde fluorescent
      labeling, and GABAergic neurotransmission to CVNs were examined using patch-clamp
      electrophysiological techniques. RESULTS: Isoflurane at concentrations of >50
      microM significantly suppressed inspiratory bursting frequency, amplitude, and
      duration. Isoflurane dose-dependently decreased the frequency and increased the
      decay time of spontaneous GABAergic inhibitory postsynaptic currents (IPSCs) in
      CVNs. To test whether the inhibition of GABAergic activity to CVNs was mediated
      by presynaptic nicotinic receptors, the nicotinic antagonist, dihydro-beta
      erythroidine in an alpha(4)beta(2)-selective concentration (3 microM), was used.
      Dihydro-beta-erythroidine (3 microM) prevented the isoflurane-evoked depression
      of spontaneous GABAergic IPSC frequency, yet isoflurane still increased the IPSC
      decay time. CONCLUSIONS: These results suggest clinically relevant concentrations
      of isoflurane inhibit brainstem respiratory rhythmogenesis, prolong inhibitory
      GABAergic postsynaptic currents and reduce GABA activity in CVNs. The decrease of
      GABAergic IPSCs frequency is dependent upon inhibition of presynaptic
      alpha(4)beta(2) nicotinic receptors.

PMID- 19095840
TI  - Arteriovenous differences in plasma dilution and the distribution kinetics of
      lactated ringer's solution.
AB  - BACKGROUND: Conventional concept suggests that infused crystalloid fluid is first
      distributed in the plasma volume and then, since the capillary permeability for
      fluid is very high, almost instantly equilibrates with the extracellular fluid
      space. We challenge whether this view is consistent with findings based on volume
      kinetic analysis. METHODS: Fifteen volunteers received an IV infusion of 15 mL/kg
      of lactated Ringer's solution during 10 min. Simultaneous arterial and venous
      blood hemoglobin (Hgb) samples were obtained and Hgb concentrations measured. The
      arteriovenous (AV) difference in Hgb dilution in the forearm was determined and a
      volume kinetic model was fitted to the series of Hgb concentrations in arterial
      and venous blood. RESULTS: The AV difference in plasma dilution was only positive
      during the infusion and for 2.5 min thereafter, which represents the period of
      net flow of fluid from plasma to tissue. Kinetic analysis showed that volume
      expansion of the peripheral fluid space began to decrease 14 min (arterial blood)
      and 20 min (venous blood) after the infusion ended. Distribution of lactated
      Ringer's solution apparently occurs much faster in the forearm than in the body
      as a whole. Therefore, the AV difference in the arm does not accurately reflect
      the distribution of Ringer's solutions or whole-body changes in plasma volume.
      CONCLUSIONS: The relatively slow whole-body distribution of lactated Ringer's
      solution, which boosts the plasma volume expansion during and for up to 30 min
      after an infusion, is probably governed by a joint effect of capillary
      permeability and differences in tissue perfusion between body regions.

PMID- 19095842
TI  - Propofol and isoflurane enhancement of tonic gamma-aminobutyric acid type a
      current in cardiac vagal neurons in the nucleus ambiguus.
AB  - BACKGROUND: General anesthesia with propofol and isoflurane induces alterations
      of the cardiovascular system, including hypotension and changes in heart rate.
      The preganglionic cardiac vagal neurons (CVNs) are one of the major central
      components controlling heart rate and autonomic regulation. In this study, we
      examined whether propofol and isoflurane act on phasic or tonic gamma
      aminobutyric acid type A (GABA(A)) receptor-mediated inhibition in CVNs. METHODS:
      CVNs were identified in vitro by retrograde fluorescent labeling. Phasic and
      tonic GABA currents in CVNs were examined using the whole cell patch-clamp
      technique. RESULTS: Propofol (10 microM) increased the membrane holding currents
      by 63 +/- 13% and prolonged the decay time of GABAergic miniature inhibitory
      postsynaptic currents (mIPSCs) from 42.3 +/- 2.8 ms in control to 61.8 +/- 4.5
      ms. Isoflurane, at concentrations of 100, 300, and 500 microM, decreased
      GABAergic mIPSCs frequency by 26.0 +/- 16%, 64.6 +/- 10.4%, and 70.5 +/- 9.8%,
      prolonged the decay time of GABAergic mIPSCs from 47.9 +/- 7.3 to 64.5 +/- 8.1
      ms, 70.3 +/- 10.4 ms, and 66.8 +/- 8.1 ms, and increased the membrane holding
      currents by 32.8 +/- 12.8%, 42.7 +/- 10%, and 39.9 +/- 3%, respectively. The
      GABAergic antagonist gabazine (25 microM) blocked GABAergic mIPSCs, but failed to
      alter the enhanced holding potential induced by propofol and isoflurane. In
      contrast, the channel blocker of GABA(A) receptors, picrotoxin (100 microM),
      reversed the propofol and isoflurane-evoked increase in membrane holding current.
      CONCLUSION: The results demonstrate that the general anesthetics propofol and
      isoflurane enhance both phasic and tonic GABA(A) receptor-mediated inhibition of
      CVNs.

PMID- 19095843
TI  - Competitive substrates for P-glycoprotein and organic anion protein transporters
      differentially reduce blood organ transport of fentanyl and loperamide:
      pharmacokinetics and pharmacodynamics in Sprague-Dawley rats.
AB  - BACKGROUND: Drug transport proteins may be instrumental in controlling the
      concentration of fentanyl at mu receptors in the brain and may provide potential
      therapeutic targets for controlling an individual response to opioid
      administration. P-glycoprotein (P-gp) efflux transporter and organic anion
      transport protein inward transporters (OATP, human; Oatp, rat) have been
      implicated in fentanyl and verapamil (only P-gp) transport across the blood-brain
      barrier. We hypothesized that transport proteins P-gp and Oatp mediate opioid
      uptake in a drug and organ-specific manner, making them excellent potential
      targets for therapeutic intervention. METHODS: Opioid (fentanyl or loperamide)
      was administered by IV infusion to Sprague-Dawley rats alone or in combination
      with competitive substrates of P-gp (verapamil) or Oatp (pravastatin, naloxone).
      Plasma, lung, and brain were collected over 10 min and at 60 min after opioid
      infusion and opioid concentration determined using liquid chromatography/mass
      spectrometry (LC/LC-MS/MS). Continuous electroencephalogram was used to determine
      the in vivo response to fentanyl and loperamide in the presence and absence of
      verapamil. RESULTS: Loperamide brain:plasma (P(B)) and lung:plasma (P(L))
      partitioning was increased two and fivefold, respectively in the presence of
      verapamil. Verapamil administration was lethal unless the loperamide dose was
      reduced by half (0.95-0.475 mg/kg). Fentanyl brain:plasma and lung:plasma were
      reduced four and sixfold, respectively, by pravastatin and naloxone, whereas
      verapamil had much less effect. Electroencephalogram results indicated that
      verapamil reduced the fentanyl-induced central nervous system (CNS) effect and
      increased the loperamide CNS effect. CONCLUSION: Protein transporters appear to
      be organ and drug-specific in vivo, affecting first-pass pulmonary uptake and CNS
      response to opioid administration. Further, data suggest that transport protein
      inhibition may prove useful for normalizing an individual response to opioids.

PMID- 19095844
TI  - Modeling the GABAergic action of etomidate on the thalamocortical system.
AB  - BACKGROUND: We have used a computational model of the thalamocortical system to
      investigate the effects of a GABAergic anesthetic (etomidate) on cerebral
      cortical and thalamic neuronal function. We examined the effects of phasic and
      tonic inhibition, as well as the relative importance of anesthetic action in the
      thalamus and cortex. METHODS: The amount of phasic GABAergic inhibition was
      adjusted in the model to simulate etomidate concentrations of between 0.25 and 2
      microM, with the concentration range producing unconsciousness assumed to be
      between 0.25 and 0.5 microM. In addition, we modeled tonic inhibition separately,
      and then phasic and tonic inhibition together. We also introduced phasic and
      tonic inhibition into the cerebral cortex and thalamus separately to determine
      the relative importance of each of these structures to anesthetic-induced
      depression of the thalamocortical system. RESULTS: Phasic inhibition decreased
      cortical neuronal firing by 11%-18% in the 0.25-0.5 microM range and by 38% at 2
      microM. Tonic inhibition produced similar depression (11%-21%) in the 0.25-0.5
      microM range but 65% depression at 2 microM; phasic and tonic inhibition combined
      produced the most inhibition (76% depression at 2 microM). When the thalamus and
      cortex were separately subjected to phasic and tonic inhibition, cortical firing
      rates decreased less compared to when both structures were targeted. In the 0.25
      0.5 microM range, cortical firing rate was minimally affected when etomidate
      action was simulated in the thalamus only. CONCLUSIONS: This computational model
      of the thalamocortical system indicated that tonic GABAergic inhibition seems to
      be more important than phasic GABAergic inhibition (especially at larger
      etomidate concentrations), although both combined had the most effect on cerebral
      cortical firing rates. Furthermore, etomidate action in the thalamus, by itself,
      does not likely explain etomidate-induced unconsciousness.

PMID- 19095845
TI  - A comparison of the molecular bases for N-methyl-D-aspartate-receptor inhibition
      versus immobilizing activities of volatile aromatic anesthetics.
AB  - BACKGROUND: Aromatic anesthetics exhibit a wide range of N-methyl-d-aspartate
      (NMDA) receptor inhibitory potencies and immobilizing activities. We sought to
      characterize the molecular basis of NMDA receptor inhibition using comparative
      molecular field analysis (CoMFA), and compare the results to those from an
      equivalent model for immobilizing activity. METHODS: Published potency data for
      14 compounds were supplemented with new values for 2 additional agents. The
      anesthetics were divided into a training set (n = 12) used to formulate the
      activity models and a test set (n = 4) used to independently assess the models'
      predictive capability. The anesthetic structures were geometry optimized using ab
      initio quantum mechanics and aligned by field-fit minimization to provide the
      best correlation between the steric and electrostatic fields of the molecules and
      one or more lead structures. Orientations that yielded CoMFA models with the
      greatest predictive capability (assessed by leave-one-out cross-validation) were
      retained. RESULTS: The final CoMFA model for the inhibition of NR1/NR2B NMDA
      receptors explained 99.3% of the variance in the observed activities of the 12
      training set agents (F(2,)(9) = 661.5, P < 0.0001). The model effectively
      predicted inhibitory potency for the training set (cross-validated r(2)(CV) =
      0.944) and 4 excluded test set compounds (predictive r(2)(Pred) = 0.966). The
      equivalent model for immobility in response to noxious stimuli explained 98.0% of
      the variance in the observed activities for the training set (F(2,)(9) = 219.2, P
      < 0.0001) and exhibited adequate predictive capability for both the training set
      (r(2)(CV) = 0.872) and test set (r(2)(Pred) = 0.926) agents. Comparison of
      pharmacophoric maps showed that several key steric and electrostatic regions were
      common to both activity models, but differences were observed in the relative
      importance of these key regions with respect to the two aspects of anesthetic
      activity. CONCLUSIONS: The similarities in the pharmacophoric maps are consistent
      with NMDA receptors contributing part of the immobilizing activity of volatile
      aromatic anesthetics.

PMID- 19095846
TI  - Tolerance to isoflurane does not occur in developing Xenopus laevis tadpoles.
AB  - INTRODUCTION: Tolerance is observed for a variety of central nervous system
      depressants including ethanol, which is an anesthetic, but has not been
      convincingly demonstrated for a potent halogenated volatile anesthetic. Failure
      to demonstrate tolerance to these agents may be the result of inadequate exposure
      to anesthetic. In this study, we exposed Xenopus laevis tadpoles to surgical
      anesthetic concentrations of isoflurane for 1 wk. METHODS: Xenopus laevis
      tadpoles were produced by in vitro fertilization, and exposed to isoflurane
      (0.59%, 0.98%, 1.52%) or oxygen for 1 wk starting from the time of fertilization.
      RESULTS: Changes in anesthetic EC(50) were small and not in a consistent
      direction. Control animals had an anesthetic EC(50) of 0.594% +/- 0.003%
      isoflurane. Tadpoles exposed to 1.52% isoflurane had a lower EC(50) than controls
      (by 16%), whereas tadpoles raised under 0.59% and 0.98% isoflurane had higher
      EC(50)s than control (by 4.7% and 7.4%, respectively). CONCLUSION: We provide the
      first description of week-long exposures of vertebrates to surgical anesthetic
      concentrations of isoflurane, and the first report of such exposures in
      developing vertebrates. Tolerance to isoflurane does not occur in developing
      Xenopus laevis tadpoles. Taken together with studies in other organisms, the
      development of tolerance to ethanol but not isoflurane suggests that mechanisms
      shared by these drugs probably do not account for the development of tolerance.

PMID- 19095847
TI  - Electrical noise in the intraoperative magnetic resonance imaging setting.
AB  - BACKGROUND: Intraoperative magnetic resonance imaging (iMRI) is a tool now
      commonly used in neurosurgery. Safe and reliable patient care in this (or any
      other) operating room setting depends on an environment, where electrical noise
      (EN) does not interfere with the operation of the electronic monitoring or
      imaging equipment. In this investigation, we evaluated the EN generated by the
      iMRI system and the anesthesia patient monitor used at this institution that
      impacts the performance of these two devices. METHODS: We measured the EN
      generated by our iMRI-compatible anesthesia patient monitor as detected by the EN
      analysis algorithm in our iMRI system. We measured the EN generated by our iMRI
      system during scanning as detected in the electrocardiogram (ECG) waveform of our
      patient monitor. We analyzed the effects on EN reduction and signal quality of
      the ECG noise filters provided in our iMRI-compatible anesthesia patient monitor.
      RESULTS: Our patient monitor generated EN that was detectable by the iMRI EN
      analysis algorithm; however, this interference was within the iMRI manufacturer's
      acceptable limits for an iMRI scan (<10% more than background system-level
      noise). In the clinical case analyzed, the iMRI generated a narrow-band low
      frequency (20 Hz) relatively high-energy EN that interfered with the ECG signal
      of our patient monitor during an iMRI scan. This EN was correlated with the
      acoustic noise from the iMRI system during the scan and was associated with the
      radio frequency (RF) and magnetic gradient pulsations of the iMRI system. The
      integrity of the ECG waveform was nearly entirely lost during a scan. The filters
      of the ECG monitor diminished but did not entirely eliminate this 20 Hz
      interference. We found that the filters alter the morphology of the ECG signal,
      which may make it difficult to identify clinically relevant ECG changes.
      CONCLUSION: The EN generated by our anesthesia patient monitor is within
      acceptable limits for the iMRI system. The iMRI generates EN which renders the
      ECG unreadable in the most commonly used filter mode. The monitor's filters
      diminish this noise but also alter the morphology of the ECG waveform. The
      anesthesiologist must be cognizant of these technical compromises and recognize
      that adjusting the ECG filters on the monitor is required to obtain a useful ECG
      signal for patient monitoring during the iMRI scan but that the diagnostic value
      of the ECG will be reduced.

PMID- 19095848
TI  - Forces applied to the maxillary incisors during video-assisted intubation.
AB  - BACKGROUND: Modern, video laryngoscopes provide an easier view of the glottis,
      possibly facilitating easier intubations. We describe an objective method for
      evaluating the benefits of video-assisted laryngoscopy, compared with standard
      techniques using force measurements. METHOD: Macintosh and video laryngoscopes
      (both Karl Storz, Tuttlingen, Germany) were used on the patients until the
      anesthesiologist was convinced he or she had the best possible view of the
      glottis. Actual intubation was only performed with the second of the
      laryngoscopes. Sensors measured the forces directly applied to the patients'
      maxillary incisors. Additionally, common subjective pre- (e.g., Mallampati) and
      intraintubation (e.g., Cormack-Lehane [C&L]) metrics of intubation difficulty
      were evaluated by the anesthesiologists. RESULTS: All patients (24 female, [50 +/
      16 yr], 20 male [56 +/- 13 yr]) included in the study were successfully
      intubated with both the classic and video laryngoscopes. The forces recorded for
      the classic Macintosh blade ranged from 0 to 87.4 N with a median of 15.3 N,
      whereas the video laryngoscope forces ranged from 0 to 45.2 N, with a median of
      2.1 N. The only factor determined to be significantly influential on the
      associated forces applied to the maxillary incisors was the laryngoscope type (P
      < 0.01). Video-assisted laryngoscopes reduced the applied forces over standard
      blades. Mallampati and C&L grade were not predictive of the forces applied.
      CONCLUSIONS: Video-assisted laryngoscopes seem beneficial when considering forces
      applied to the maxillary incisors as an objective metric of intubation
      difficulty. In this study, we could not support that Mallampati and C&L grades
      predict the forces that are applied to the maxillary incisors.

PMID- 19095849
TI  - What determines the efficacy of forced-air warming systems? A manikin evaluation
      with upper body blankets.
AB  - BACKGROUND: Forced-air warming has gained acceptance as an effective means to
      prevent perioperative hypothermia. However, little is known about the influence
      of air flow and air temperature at the nozzle and the influence of heat
      distribution in the blankets on the efficacy of these systems. METHODS: We
      conducted a manikin study with heat flux transducers using five forced-air
      warming systems to determine the factors that are responsible for heat transfer
      from the blanket to the manikin. RESULTS: There was no relation between air
      temperature at the nozzle of the power unit and the resulting heat transfer.
      There was also no relation between the air flow at the nozzle of the power unit
      and the resulting heat transfer. However, all blankets performed best at high air
      flows above 19 L/s. The heat exchange coefficient, the mean temperature gradient
      between the blanket and the manikin correlated positively with the resulting heat
      transfer and the difference between the minimal and maximal blanket temperature
      correlated negatively with the resulting heat transfer. CONCLUSIONS: The efficacy
      of forced-air warming systems is primarily determined by the blanket. Modern
      power units provide sufficient heat energy to maximize the ability of the blanket
      to warm the patient. Optimizing blanket design by optimizing the mean temperature
      gradient between the blanket and the manikin (or any other surface) with a very
      homogeneous temperature distribution in the blanket will enable the manufacturers
      to develop better forced-air warming systems.

PMID- 19095850
TI  - The efficacy of a resistive heating under-patient blanket versus a forced-air
      warming system: a randomized controlled trial.
AB  - BACKGROUND: We compared temperature changes in patients undergoing hip
      replacement during warming with a resistive heating blanket or air-forced system.
      METHODS: Fifty-six patients were enrolled. Patients were randomly allocated to
      the "forced-air group" (forced-air system) or to the "heating-blanket group"
      (resistive heating under-patient blanket). RESULTS: Baseline tympanic
      temperatures were 36.0 +/- 0.6 degrees C in the forced-air group and 36.1 +/- 0.4
      degrees C in the heating-blanket group (P > 0.05). At the end of surgery tympanic
      temperatures were 35.3 +/- 0.5 degrees C in the forced-air group and 35.1 +/- 0.6
      degrees C in the heating-pad group (P > 0.05). CONCLUSIONS: We demonstrated that,
      using either a resistive heating-blanket or forced-air warming systems, patients
      ended surgery in mild hypothermia after elective total hip replacement, but
      without significant differences between these two warming devices.

PMID- 19095851
TI  - A novel process for introducing a new intraoperative program: a multidisciplinary
      paradigm for mitigating hazards and improving patient safety.
AB  - BACKGROUND: Since the Institute of Medicine's report, To Err is Human, was
      published, numerous interventions have been designed and implemented to correct
      the defects that lead to medical errors and adverse events; however, most efforts
      were largely reactive. Safety, communication, team performance, and efficiency
      are areas of care that attract a great deal of attention, especially regarding
      the introduction of new technologies, techniques, and procedures. We describe a
      multidisciplinary process that was implemented at our hospital to identify and
      mitigate hazards before the introduction of a new technique: high-dose-rate
      intraoperative radiation therapy, (HDR-IORT). METHODS: A multidisciplinary team
      of surgeons, anesthesiologists, radiation oncologists, physicists, nurses,
      hospital risk managers, and equipment specialists used a structured process that
      included in situ clinical simulation to uncover concerns among care providers and
      to prospectively identify and mitigate defects for patients who would undergo
      surgery using the HDR-IORT technique. RESULTS: We identified and corrected 20
      defects in the simulated patient care process before application to actual
      patients. Subsequently, eight patients underwent surgery using the HDR-IORT
      technique with no recurrence of simulation-identified or unanticipated defects.
      CONCLUSION: Multiple benefits were derived from the use of this systematic
      process to introduce the HDR-IORT technique; namely, the safety and efficiency of
      care for this select patient population was optimized, and this process mitigated
      harmful or adverse events before the inclusion of actual patients. Further work
      is needed, but the process outlined in this paper can be universally applied to
      the introduction of any new technologies, treatments, or procedures.

PMID- 19095852
TI  - The new Food and Drug Administration drug package insert: implications for
      patient safety and clinical care.
AB  - The United States Food and Drug Administration (FDA) is the scientific,
      regulatory, and public health agency that regulates many products, including food
      products, drugs, medical devices, radiation emitting devices, and cosmetics for
      the federal government of the United States. The FDA's mission is to assure that
      consumer products made and sold in the United States are safe, effective, and
      pure. The purpose of the package insert (also known as prescription drug product
      insert or professional labeling) is to provide detailed drug information compiled
      and distributed by the drug manufacturer, after FDA review and approval. In 2006,
      the standard format for the package insert was changed in an attempt to make it
      more user-friendly and a more efficient resource tool for practitioners.
      According to the Institute of Medicine, in-hospital adverse drug reactions occur
      at a rate of 400,000 per year and incur $3.5 billion of extra hospital expense.
      It is expected that the new package insert format will enhance rapid access to
      important pharmacologic information and improve patient safety by decreasing
      medication errors.

PMID- 19095853
TI  - Interruptions and blood transfusion checks: lessons from the simulated operating
      room.
AB  - Interruptions occur frequently in the operating room with both positive and
      negative consequences. Interruptions can distract anesthesiologists from safety
      critical tasks, such as the pretransfusion blood check. In a simulated operating
      room, 12 anesthesiologists requested blood as part of a "bleeding patient"
      scenario. They were distracted while their assistant accepted delivery of the
      product and began transfusing without performing the standard check.
      Anesthesiologists who immediately engaged with the interruption failed to notice
      the omission, whereas those who rejected or deferred the interruption all noted
      and remedied the omitted check (P < 0.05). We discuss the role of displays and
      strategies on safety.

PMID- 19095854
TI  - The effect of endothelin-1 on alveolar fluid clearance and pulmonary edema
      formation in the rat.
AB  - BACKGROUND: Endothelin-1 (ET-1) is thought to play a pivotal role in pulmonary
      edema formation. The underlying mechanisms remain uncertain but may include
      alterations in capillary pressure and vascular permeability. There are no studies
      investigating whether ET-1 also affects alveolar fluid clearance which is the
      primary mechanism for the resolution of pulmonary edema. Therefore, we performed
      this study to clarify effects of ET-1 on alveolar reabsorption and fluid balance
      in the rat lung. METHODS: Alveolar fluid clearance was measured in fluid
      instilled rat lungs using a 5% albumin solution with or without ET-1 (10(-7) M)
      and/or amiloride (100 microM). Net alveolar fluid balance, time course of edema
      formation, pulmonary capillary pressure, and alveolar permeability to albumin
      were measured in the isolated, ventilated, constant pressure perfused rat lung
      with or without ET-1 (0.8 nM) added to the perfusate. RESULTS: In the fluid
      instilled lung, ET-1 reduced alveolar fluid clearance by about 65%, an effect
      that was related to a decrease in amiloride-sensitive transepithelial Na(+)
      transport (P < 0.001). The ET-1-induced inhibition was completely prevented by
      the endothelin B receptor antagonist BQ788 (P = 0.006), whereas the endothelin A
      receptor antagonist BQ123 had no effect (P = 0.663). In the isolated, ventilated,
      perfused rat lung ET-1 caused a net accumulation of alveolar fluid by about 20%
      (P = 0.011 vs control), whereas lungs of control rats cleared about 20% of the
      instilled fluid. ET-1 increased pulmonary capillary pressure (+9.4 cm H(2)O),
      decreased perfusate flow (-81%), accelerated lung weight gain and reduced lung
      survival time (P < 0.001). Permeability to albumin was not significantly affected
      by ET-1 (P = 0.24). CONCLUSION: ET-1 inhibits alveolar fluid clearance of
      anesthetized rats by inhibition of amiloride-sensitive epithelial Na(+) channels.
      The inhibitory effect of ET-1 results from activation of the endothelin B
      receptor. These findings suggest a mechanism by which ET-1, in addition to
      increasing capillary pressure, contributes to pulmonary edema formation.

PMID- 19095855
TI  - Acute interstitial pneumonia-Hamman-Rich syndrome: clinical characteristics and
      diagnostic and therapeutic considerations.
AB  - BACKGROUND: Acute interstitial pneumonia is a rapidly progressive disease
      frequently leading to respiratory failure and mechanical ventilation. The
      prognosis is usually poor despite aggressive diagnostic and treatment efforts.
      METHODS: In this retrospective cohort survey, we enrolled patients with hypoxemic
      respiratory failure who met predefined criteria of acute idiopathic interstitial
      pneumonia. Patients' records, radiologic studies, and pathologic specimens were
      reviewed. All data were recorded in each patient's study file and subsequently
      analyzed. RESULTS: Our cohort consisted of 5 men and 4 women with a mean age of
      69.4 yr (55-80 yr). The chest radiograph in all patients progressed to diffuse
      bilateral infiltrates over a 12-day course. All nine patients had histological
      proof of diffuse alveolar damage consistent with acute interstitial pneumonia,
      obtained by either transbronchial biopsy or open lung biopsy. All patients
      required admission to the medical intensive care unit and mechanical ventilation.
      The mortality rate was 100%, and patients died within 5-26 days of their
      admission to the unit. CONCLUSIONS: Acute interstitial pneumonia (Hamman-Rich
      syndrome) is an idiopathic, rapidly progressive and, at times, fatal form of
      interstitial lung disease. A transbronchial biopsy is a logical first diagnostic
      step, to be followed by an open lung biopsy, if necessary. Response to
      corticosteroids in our series was minimal. In patients who fail to respond to
      conventional therapy and are otherwise appropriate candidates, lung
      transplantation may be considered as an additional alternative.

PMID- 19095856
TI  - Etomidate infusion in the critical care setting for suppressing the acute phase
      of Cushing's syndrome.
AB  - A 17-year-old, 55 kg girl was referred to the endocrinology department of a
      university hospital to determine the etiology of suspected Cushing's syndrome.
      The patient was treated with oral ketoconazole for 3 days, but a rapid and severe
      elevation in her liver function test results led to selection of IV etomidate as
      a therapeutic option. This approach led to decreasing levels of serum cortisol,
      and the patient was able to tolerate surgical adrenalectomy.

PMID- 19095857
TI  - A randomized trial of maximum cephalad sensory blockade with single-shot spinal
      compared with combined spinal-epidural techniques for cesarean delivery.
AB  - BACKGROUND: Previous studies have shown more extensive cephalad sensory blockade
      in women receiving combined spinal-epidural (CSE) anesthesia compared with single
      shot spinal (SSS) anesthesia for elective cesarean delivery. It has been
      postulated that introduction of the epidural needle during CSE disturbs the
      negative pressure in the epidural space, resulting in relatively greater
      cerebrospinal fluid (CSF) pressure and increased spread of intrathecal local
      anesthetic. We tested the hypothesis that CSE results in more extensive cephalad
      sensory blockade than SSS anesthesia and that loss-of-resistance during
      initiation of CSE anesthesia increases CSF pressure compared with SSS. METHODS:
      Thirty parturients scheduled for elective cesarean delivery were enrolled in this
      randomized, double-blind study. Patients received either SSS or CSE anesthesia
      with equal doses of intrathecal anesthetic (hyperbaric bupivacaine 12 mg,
      fentanyl 10 microg and morphine 200 microg). Before the intrathecal injection,
      the CSF pressure was measured with a fiberoptic pressure sensor. Maximum cephalad
      sensory blockade to pinprick, cold and touch was measured. The total dose of
      phenylephrine required to maintain baseline arterial blood pressure was also
      recorded. RESULTS: There were no significant differences in the median
      (interquartile range) pinprick sensory block height [T4 (T4-2) vs T3 (T4-1)] or
      CSF pressures [6 (4-12) vs 9 (8-12) mm Hg] between the SSS and CSE groups. There
      were no significant correlations between CSF pressure and block height or total
      dose of phenylephrine. CONCLUSION: The SSS and CSE techniques inserted in the
      lateral decubitus position resulted in similar extent of sensory blockade and CSF
      pressure. These findings suggest that altering the intrathecal dose is not
      necessary and that any difference in intrathecal pressure associated with initial
      placement of an epidural needle in the epidural space during CSE anesthesia is
      clinically inconsequential.

PMID- 19095858
TI  - A randomized trial of breakthrough pain during combined spinal-epidural versus
      epidural labor analgesia in parous women.
AB  - BACKGROUND: There is controversy regarding the benefits and risks of combined
      spinal-epidural compared with epidural analgesia (CSE, EPID) for labor analgesia.
      We hypothesized that CSE would result in fewer patient requests for top-up doses
      compared to EPID. METHODS: One-hundred ASA physical status I or II parous women
      at term in early labor (<5 cm cervical dilation) requesting analgesia were
      randomized in double-blind fashion to the EPID group (epidural bupivacaine 2.5
      mg/mL, 3 mL, followed by bupivacaine 1.25 mg/mL, 10 mL with fentanyl 50 microg)
      or the CSE group (intrathecal bupivacaine 2.5 mg with fentanyl 25 microg). Both
      groups received identical infusions of bupivacaine 0.625 mg/mL with fentanyl 2
      microg/mL at 12 mL/h. The primary outcome variable was the number of top-up doses
      requested to treat breakthrough pain. RESULTS: There was no significant
      difference between the two groups in the percentage of patients requesting top-up
      doses (44% CSE vs 51% EPID; 95% confidence interval of the difference -28% to
      +14%) nor in the need for multiple top-up doses (14% CSE vs 15% EPID). Visual
      analog scale scores were lower in the CSE group compared to the EPID group at 10
      min after initiation of analgesia [median 0 cm (0, 0) vs 4 cm (1, 6)
      respectively, P < 0.001] and at 30 min [0 cm (0, 0) vs 0 cm (0, 1), respectively,
      P = 0.03]. CONCLUSIONS: We did not find a difference in the need for top-up doses
      in parous patients; however, CSE provided better analgesia in the first 30 min
      compared to EPID.

PMID- 19095859
TI  - Failure of augmentation of labor epidural analgesia for intrapartum cesarean
      delivery: a retrospective review.
AB  - In this study, we aimed to identify the incidence and predictive factors
      associated with failed labor epidural augmentation for cesarean delivery. Data of
      parturients, who had received neuraxial labor analgesia and who subsequently
      required intrapartum cesarean delivery during an 18-mo period, were
      retrospectively studied. Predictors associated with failure of extension of
      epidural analgesia in the presence of adequate time for onset of epidural
      anesthesia were identified by univariate logistic regression. Of the 1025
      parturients, 1.7% had failed epidural extension. Predictors of failed epidural
      anesthesia included initiation of labor analgesia with plain epidural technique
      (compared to combined spinal-epidural) (P = 0.001), >or=2 episodes of
      breakthrough pain during labor (P < 0.001) and prolonged duration of neuraxial
      labor analgesia (P = 0.02).

PMID- 19095860
TI  - Performance of certified registered nurse anesthetists and anesthesiologists in a
      simulation-based skills assessment.
AB  - BACKGROUND: Anesthesiologists and certified registered nurse anesthetists (CRNAs)
      must acquire the skills to recognize and manage a variety of acute intraoperative
      emergencies. A simulation-based assessment provides a useful and efficient means
      to evaluate these skills. In this study, we evaluated and compared the
      performance of board-certified anesthesiologists and CRNAs managing a set of
      simulated intraoperative emergencies. METHODS: We enrolled 26 CRNAs and 35 board
      certified anesthesiologists in a prospective, randomized, single-blinded study.
      These 61 specialists each managed 8 of 12 randomly selected, scripted,
      intraoperative simulation exercises. Participants were expected to recognize and
      initiate appropriate therapy for intraoperative events during a 5-min period. Two
      primary raters scored 488 simulation exercises (61 participants x 8 encounters).
      RESULTS: Anesthesiologists achieved a modestly higher mean overall score than
      CRNAs (66.6% +/- 11.7 [range = 41.7%-86.7%] vs 59.9% +/- 10.2 [range = 38.3%
      80.4%] P < 0.01). There were no significant differences in performance between
      groups on individual encounters. The raters were consistent in their
      identification of key actions. The reliability of the eight-scenario assessment,
      with two raters for each scenario, was 0.80. CONCLUSION: Although
      anesthesiologists, on average, achieved a modestly higher overall score, there
      was marked and similar variability in both groups. This wide range suggests that
      certification in either discipline may not yield uniform acumen in management of
      simulated intraoperative emergencies. In both groups, there were practitioners
      who failed to diagnose and treat simulated emergencies. If this is reflective of
      clinical practice, it represents a patient safety concern. Simulation-based
      assessment provides a tool to determine the ability of practitioners to respond
      appropriately to clinical emergencies. If all practitioners could effectively
      manage these critical events, the standard of patient care and ultimately patient
      safety could be improved.

PMID- 19095861
TI  - Six-year follow-up on work force and finances of the United States anesthesiology
      training programs: 2000 to 2006.
AB  - BACKGROUND: In the mid 1990s, interest in the field of anesthesiology decreased
      significantly among medical students, resulting in a decreasing resident class
      size and, subsequently, fewer anesthesiologists entering the United States
      workforce. This apparent practitioner shortage was associated with increased
      salary demands, which placed anesthesiology training departments in financial
      jeopardy. Starting in 1999, a survey was sent to the department chairs of the
      United States anesthesiology training programs to assess the status of faculty
      and finances of their departments. Follow-up surveys have been conducted each
      year thereafter. We present the results of the 2006 survey and 7 yr trend data.
      METHODS: Surveys were distributed by e-mail in September 2006 to anesthesiology
      department chairs of the United States training programs. The responses were
      received by e-mail. Descriptive statistics were performed on responder data. In
      addition, a linear regression model to predict institutional support was
      developed. RESULTS: One-hundred-eighteen departments were surveyed with a
      response rate of 61%. There were an average of 4 open faculty positions in the
      71% of the departments reporting open faculty positions. This would imply an
      overall 5% open position rate, down from 10% in 2000. Of the 96% of departments
      who employ certified registered nurse anesthetists, 70% had an average of 4 open
      positions, or approximately 11% shortage. The average department received
      $5,500,000 in total institutional support annually ($120,000/faculty). When the
      portion of this support provided for certified registered nurse anesthetists was
      removed, the average amount received was $4,600,000 or $100,000/faculty. This is
      a 10% increase over the previous year and an approximate 300% increase over the
      year 2000. Faculty academic time averaged 18% (where 20% is 1 day per week). The
      departments billed an average of 12,200 U/faculty/year. The average anesthesia
      unit value collected was $31/unit, while departments would require $46/unit to
      meet expenses. In a linear regression model, clinical revenue per unit billed
      minus expenses per unit billed predicted faculty support per full-time
      equivalent. CONCLUSION: This current survey reveals a continuing need for
      institutional support to keep anesthesiology training departments financially
      solvent. The amount of support is associated with the reimbursement for
      anesthesia work. There is also a continuing, but decreasing, number of open
      faculty anesthesiologist positions nationwide.

PMID- 19095862
TI  - Airway scope and StyletScope for tracheal intubation in a simulated difficult
      airway.
AB  - BACKGROUND: Direct laryngoscopy is difficult when the cervical spine is
      immobilized. The Airway Scope and StyletScope are new laryngoscopes designed to
      facilitate intubation under these circumstances. Thus, in patients wearing a
      rigid cervical collar to simulate a difficult airway, we tested the hypothesis
      that the intubation success rates of the Airway Scope and StyletScope are
      similar, but that intubation with Airway Scope is faster. METHODS: Adult patients
      requiring tracheal intubation as part of anesthesia were enrolled. After
      anesthesia induction and muscle relaxation, patients' necks were stabilized with
      a rigid Philadelphia collar and patients were randomly assigned to tracheal
      intubation with Airway Scope (n = 50) or StyletScope (n = 50). Overall intubation
      success rate, time required for intubation, the number of attempts required for
      successful intubation, and airway complications related to intubation were
      recorded. RESULTS: Overall intubation success rates were 98% with Airway Scope
      and 96% with StyletScope. Intubation was 19 s faster with Airway Scope (32[8] s;
      mean) versus StyletScope (51[29] s). The number of required intubation attempts
      was similar with each device: 26/18/5 (first/second/third attempt) for Airway
      Scope versus 26/17/5 for StyletScope. The incidence of mucosal trauma and lip
      injury was similar, except esophageal intubation occurred only with StyletScope
      (n = 6); neither dental injury nor hypoxia occurred. CONCLUSIONS: Both the Airway
      Scope and StyletScope offer high success rates in a simulated difficult airway
      achieved by a rigid collar. However, the Airway Scope is faster and less likely
      to cause esophageal intubation.

PMID- 19095864
TI  - The effects of beta-adrenoceptor antagonists on proinflammatory cytokine
      concentrations after subarachnoid hemorrhage in rats.
AB  - BACKGROUND: Proinflammatory cytokines increase in cerebrospinal fluid (CSF) after
      subarachnoid hemorrhage (SAH). Recent evidence suggested that beta-adrenoceptor
      antagonist could reduce proinflammatory cytokines. We conducted the present study
      to examine whether beta-adrenoceptor antagonists would reduce proinflammatory
      cytokine concentrations after SAH in rats. METHODS: In Experiment 1, to
      investigate the time course of interleukin-6 (IL-6) and tumor necrosis factor
      alpha (TNF-alpha), rats were randomized into groups: 1, 3, 6, and 12 h after SAH
      or sham operation. CSF and blood samples were obtained at each time point. In
      Experiment 2, to investigate the effects of beta-adrenoceptor antagonists on the
      IL-6 and TNF-alpha concentrations, rats were randomized into groups: 1) control
      group: SAH + normal saline, 2) propranolol group: SAH + propranolol, 3)
      metoprolol group: SAH + metoprolol, and 4) butoxamine group: SAH + butoxamine
      (beta(2)-adrenoceptor antagonist). CSF and blood samples were obtained 6 h after
      SAH. IL-6 and TNF-alpha concentrations in samples were measured. RESULTS: In
      Experiment 1, CSF IL-6 concentrations in the SAH groups increased markedly and
      peaked at 6 h after SAH, whereas CSF TNF-alpha concentrations in the SAH groups
      were consistently low. In Experiment 2, CSF IL-6 concentrations in the
      propranolol and butoxamine groups were significantly lower compared with those in
      the control group (P < 0.01 and P < 0.05 for each group). Plasma IL-6, CSF TNF
      alpha, and plasma TNF-alpha concentrations were comparable in all four groups.
      CONCLUSIONS: CSF IL-6 concentrations increased in the acute stage of SAH and beta
      adrenoceptor antagonists with a beta(2)-adrenoceptor blocking action suppressed
      this elevation of IL-6 concentrations after SAH in rats.

PMID- 19095863
TI  - Postischemic brain injury is attenuated in mice lacking the beta2-adrenergic
      receptor.
AB  - BACKGROUND: Several beta-adrenergic receptor (betaAR) antagonists have been shown
      to have neuroprotective effects against cerebral ischemia. However, clenbuterol,
      a beta(2)AR agonist, was shown to have neuroprotective activity by increasing
      nerve growth factor expression. We used beta(2)AR knockout mice and a beta(2)
      selective antagonist to test the effect of loss of beta(2)ARs on outcome from
      transient focal cerebral ischemia. METHODS: Ischemia was induced by the
      intraluminal suture method, for 60 min of middle cerebral artery occlusion (MCAO)
      followed by 24 h reperfusion. Neurological score was determined at 24 h
      reperfusion and infarct size was determined by cresyl violet or 2,3,5
      triphenyltetrazolium chloride staining. beta(2)AR knockout mice and wild-type
      congenic FVB/N controls were studied, as well as 2 groups of wild type mice given
      either ICI 118,551 (0.2 mg/kg) or 0.9% saline intraperitoneally 30 min before
      MCAO (n = 10 per group). Changes in expression of heat shock protein (Hsp)72
      after ischemia were examined by immunohistochemistry and western blots. RESULTS:
      Compared with wild type littermates, infarct volume was decreased by 22.3% in
      beta(2)AR knockout mice (39.7 +/- 10.7 mm(3) vs 51.0 +/- 11.4 mm(3), n =
      10/group, P = 0.034) after 60 min of MCAO followed by 24 h reperfusion.
      Pretreatment with a beta(2)AR selective antagonist, ICI 118,551, also decreased
      infarct size significantly, by 25.1%, compared with the saline control (32.8 +/-
      11.9 mm(3) vs 43.8 +/- 10.3 mm(3), n = 10/group, P = 0.041). Neurological scores
      were also significantly improved in mice lacking the beta(2)AR or pretreated with
      ICI 118,551. After cerebral ischemia, total levels of Hsp72 and the number of
      Hsp72 immunopositive cells were greater in mice lacking beta(2) AR. CONCLUSION:
      Brain injury is reduced and neurological outcome improved after MCAO in mice
      lacking the beta(2)AR, or in wild type mice pretreated with a selective beta(2)AR
      antagonist. This is consistent with a shift away from prosurvival signaling to
      prodeath signaling in the presence of beta(2)AR activation in cerebral ischemia.
      Protection is associated with higher levels of Hsp72, a known antideath protein.
      The effect of beta(2)AR signaling in the setting of cerebral ischemia is complex
      and warrants further study.

PMID- 19095865
TI  - The Ninth Annual Conference of the Indian Society of Neuroanaesthesiology and
      Critical Care, Hyderabad, India, February 9-10, 2008.

PMID- 19095866
TI  - Cardiovascular safety of the cyclooxygenase-2 selective inhibitors parecoxib and
      valdecoxib in the postoperative setting: an analysis of integrated data.
AB  - BACKGROUND: Studies of parecoxib, the inactive prodrug of the cyclooxygenase-2
      selective inhibitor valdecoxib, and valdecoxib for postoperative pain relief in
      patients undergoing coronary artery bypass graft surgery revealed an increased
      risk of cardiovascular (CV) adverse events compared with placebo. We conducted
      this study to address whether parecoxib and valdecoxib increased CV risk in
      noncardiac surgery patients. METHODS: A pooled post hoc analysis was conducted
      using 2 large datasets: 17 controlled trials of parecoxib for noncardiac studies
      and 32 studies, including the 17 noncardiac parecoxib studies plus 15 studies of
      valdecoxib. The 32-study dataset provided 95% power to detect a twofold increase
      in the incidence of CV adverse events assuming a placebo group incidence of 1%
      (estimated from previous study data), and 69% power to detect a twofold increase
      from a 0.5% incidence. RESULTS: The incidence of total CV events for the 17
      parecoxib studies was 0.44% (13 of 2966) in patients who received parecoxib and
      0.37% (7 of 1915) in those receiving placebo (P > 0.20). In the analysis of 32
      studies, the incidence of total CV events was 0.40% (21 of 5285) in the
      parecoxib/valdecoxib group compared with 0.50% (16 of 3226) in the placebo group
      (P > 0.20). No significant differences in the incidence of total or any
      individual CV event category were observed between the parecoxib or
      parecoxib/valdecoxib and placebo groups in the two analyses. When patients were
      stratified by number of baseline CV risk factors, no significant difference in CV
      events was detected in parecoxib/valdecoxib patients compared with placebo.
      CONCLUSIONS: In the largest analysis of the CV risk of cyclooxygenase selective
      inhibitors or nonsteroidal antiinflammatory drugs for perioperative pain
      management, parecoxib and valdecoxib were not found to increase the risk of CV
      adverse events after noncardiac surgery.

PMID- 19095867
TI  - The effects of smoking status on opioid tapering among patients with chronic
      pain.
AB  - OBJECTIVE: The primary aim of this study was to determine if smoking status
      affected the ability of patients with chronic pain to reduce opioid consumption
      during a 3-wk pain rehabilitation program. Secondary aims included determining
      the associations between smoking status, admission opioid use, and pain severity.
      METHODS: We used a retrospective, repeated measures design to assess pre- and
      post-treatment outcomes in a consecutive series of patients admitted to a 3-wk,
      outpatient pain treatment program from September 2003 through February 2007.
      Outcome measures included the frequency of successful opioid tapering, pain
      severity subscale of the Multidisciplinary Pain Inventory, and program completion
      status. RESULTS: The study cohort included 1241 patients (women 928); 313 (25%)
      smokers, 294 (24%) former smokers, and 634 (51%) never smokers. There were more
      smokers using opioids at admission (P < 0.001) compared to former and never
      smokers. Likewise, the mean morphine equivalent dose (P = 0.013) and pain
      severity scores (P < 0.001) of smokers were higher compared to former and never
      smokers. The success of opioid tapering did not depend on smoking status, and all
      groups experienced significant reductions in pain severity at program completion
      (P < 0.001). However, a higher proportion of smokers did not complete treatment
      (P < 0.001). CONCLUSIONS: For patients completing a pain rehabilitation program,
      most were able to eliminate opioid use, regardless of smoking status. However,
      significantly more smokers did not complete treatment. The most frequent reasons
      for program noncompletion included discrepant expectations of treatment, acute
      illness, and psychosocial stressors.

PMID- 19095868
TI  - Biochemical and biological properties of 4-(3-phenyl-[1,2,4] thiadiazol-5-yl)
      piperazine-1-carboxylic acid phenylamide, a mechanism-based inhibitor of fatty
      acid amide hydrolase.
AB  - Fatty acid amide hydrolase (FAAH) is an integral membrane enzyme within the
      amidase-signature family. It catalyzes the hydrolysis of several endogenous
      biologically active lipids, including anandamide (arachidonoyl ethanolamide),
      oleoyl ethanolamide, and palmitoyl ethanolamide. These endogenous FAAH substrates
      have been shown to be involved in a variety of physiological and pathological
      processes, including synaptic regulation, regulation of sleep and feeding,
      locomotor activity, pain and inflammation. Here we describe the biochemical and
      biological properties of a potent and selective FAAH inhibitor, 4-(3-phenyl
      [1,2,4]thiadiazol-5-yl)-piperazine-1-carboxylic acid phenylamide (JNJ-1661010).
      The time-dependence of apparent IC(50) values at rat and human recombinant FAAH,
      dialysis and mass spectrometry data indicate that the acyl piperazinyl fragment
      of JNJ-1661010 forms a covalent bond with the enzyme. This bond is slowly
      hydrolyzed, with release of the piperazinyl fragment and recovery of enzyme
      activity. The lack of inhibition observed in a rat liver esterase assay suggests
      that JNJ-1661010 is not a general esterase inhibitor. JNJ-1661010 is >100-fold
      preferentially selective for FAAH-1 when compared to FAAH-2. JNJ-1661010 dose
      dependently increases arachidonoyl ethanolamide, oleoyl ethanolamide, and
      palmitoyl ethanolamide in the rat brain. The compound attenuates tactile
      allodynia in the rat mild thermal injury model of acute tissue damage and in the
      rat spinal nerve ligation (Chung) model of neuropathic pain. JNJ-1661010 also
      diminishes thermal hyperalgesia in the inflammatory rat carrageenan paw model.
      These data suggest that FAAH inhibitors with modes of action similar to JNJ
      1661010 may be useful clinically as broad-spectrum analgesics.

PMID- 19095869
TI  - The efficacy of ilioinguinal-iliohypogastric and intercostal nerve co-blockade
      for postoperative pain relief in kidney recipients.
AB  - BACKGROUND: Postoperative pain is severe in patients undergoing renal
      transplantation. Systemic analgesia may produce complications as a result of
      impaired renal function. We investigated whether combined lower intercostal and
      Ilioinguinal-Iliohypogastric (IG-IH) nerve block might improve the quality of
      analgesia and reduce morphine consumption during the first 24 h after surgery.
      METHODS: Forty-two patients, scheduled as kidney transplant recipients were
      randomized into two equal groups and were anesthetized with the same technique.
      After surgery IG-IH, T11 and T12 intercostal nerves on the side of surgery were
      blocked by bupivacaine 0.5%. The control group was not blocked. Postoperative
      pain and total amount of morphine consumption were recorded by a person who was
      blinded to the allocation. RESULTS: There were significant differences in median
      visual analog scale scores (25th-75th) measurements at all time points in the
      study groups (P < 0.05). The total amount of morphine consumption during 24 h was
      12.7 +/- 10.5 mg in the blocked group compared with 34.9 +/- 5.9 mg in the
      nonblocked group (P < 0.001). CONCLUSIONS: Combined IG-IH and lower intercostal
      nerves blockade after renal transplantation significantly reduced postoperative
      pain and opioid consumption.

PMID- 19095871
TI  - The effects of local anesthetic concentration and dose on continuous
      infraclavicular nerve blocks: a multicenter, randomized, observer-masked,
      controlled study.
AB  - BACKGROUND: It remains unclear whether local anesthetic concentration or total
      drug dose is the primary determinant of continuous peripheral nerve block
      effects. The only previous investigation, involving continuous popliteal-sciatic
      nerve blocks, specifically addressing this issue reported that insensate limbs
      were far more common with higher volumes of relatively dilute ropivacaine
      compared with lower volumes of relatively concentrated ropivacaine. However, it
      remains unknown if this relationship is specific to the sciatic nerve in the
      popliteal fossa or whether it varies depending on anatomic location. We therefore
      tested the null hypothesis that providing ropivacaine at different concentrations
      and rates, but at an equal total basal dose, produces comparable effects when
      used in a continuous infraclavicular brachial plexus block. METHODS:
      Preoperatively, an infraclavicular catheter was inserted using the coracoid
      approach in patients undergoing moderately painful orthopedic surgery distal to
      the elbow. Patients were randomly assigned to receive a postoperative perineural
      ropivacaine infusion of either 0.2% (basal 8 mL/h, bolus 4 mL) or 0.4% (basal 4
      mL/h, bolus 2 mL) through the second postoperative day. Both groups, therefore,
      received 16 mg of ropivacaine each hour with a possible addition of 8 mg every 30
      min via a patient-controlled bolus dose. Our primary end point was the incidence
      of an insensate limb during the 24-h period beginning the morning after surgery.
      Secondary end points included analgesia and patient satisfaction. RESULTS:
      Patients given 0.4% ropivacaine (n = 27) experienced an insensate limb, a mean
      (sd) of 1.8 (1.6) times, compared with 0.6 (0.9) times for subjects receiving
      0.2% ropivacaine (n = 23; estimated difference = 1.2 episodes, 95% confidence
      interval, 0.5-1.9 episodes; P = 0.001). Satisfaction with postoperative analgesia
      (scale 0-10, 10 = highest) was scored a median (25th-75th percentiles) of 10.0
      (8.0-10.0) in Group 0.2% and 7.0 (5.3-8.9) in Group 0.4% (P = 0.018). Analgesia
      was similar in each group. CONCLUSIONS: For continuous infraclavicular nerve
      blocks, local anesthetic concentration and volume influence perineural infusion
      effects in addition to the total mass of local anesthetic administered. Insensate
      limbs were far more common with smaller volumes of relatively concentrated
      ropivacaine. This is the opposite of the relationship previously reported for
      continuous popliteal-sciatic nerve blocks. The interaction between local
      anesthetic concentration and volume is thus complex and varies among catheter
      locations.

PMID- 19095872
TI  - An evaluation of the epidural catheter position by epidural nerve stimulation in
      conjunction with continuous epidural analgesia in adult surgical patients.
AB  - BACKGROUND: The epidural stimulation test to confirm epidural catheter position
      has been described as being simple, fast, and reliable. We evaluated the
      feasibility of the epidural stimulation test and its potential in contributing to
      effective postoperative continuous epidural analgesia. METHODS: Thirty adult
      patients (ASA I-III) undergoing major abdominal surgery or thoracotomy were to
      receive continuous epidural analgesia at a thoracic level postoperatively. The
      epidural stimulation test was performed after catheter placement, after local
      anesthetic boluses, and during epidural analgesia, up to six times in each
      patient. Catheter positions were verified by epidurography (before start of
      epidural analgesia and again on the second postoperative day). RESULTS: Several
      technical issues (e.g., need to flush catheter with saline in order to maintain
      adequate stimulation during >25% of all measurements) and interpretation problems
      (e.g., interference of respiratory activity [n = 6]) made the implementation of
      the epidural stimulation test rather time consuming, both at the time of catheter
      placement and during epidural analgesia. Immediately after catheter placement
      (before test dose) the epidural stimulation test did not identify four of four
      catheters positioned outside the spinal canal. In addition, the initial epidural
      stimulation test indicated a possible intrathecal or paravertebral placement in 3
      of 25 catheters correctly positioned in the epidural space. During 107 of 122
      (88%) measurements with the catheter tip situated epidurally and with preceding
      or simultaneous administration of epidural local anesthetic, the epidural
      stimulation test elicited a motor response. Continuous epidural analgesia
      provided adequate pain relief in all 25 patients having positive epidurography.
      CONCLUSIONS: The epidural stimulation test was often associated with technical
      difficulties and interpretation problems. The role of the repeated use of the
      epidural stimulation test for quality assurance in patients undergoing
      postoperative continuous epidural analgesia remains undetermined.

PMID- 19095870
TI  - The effect of intravenous lidocaine on brain activation during non-noxious and
      acute noxious stimulation of the forepaw: a functional magnetic resonance imaging
      study in the rat.
AB  - BACKGROUND: Lidocaine can alleviate acute as well as chronic neuropathic pain at
      very low plasma concentrations in humans and laboratory animals. The mechanism(s)
      underlying lidocaine's analgesic effect when administered systemically is poorly
      understood but clearly not related to interruption of peripheral nerve
      conduction. Other targets for lidocaine's analgesic action(s) have been
      suggested, including sodium channels and other receptor sites in the central
      rather than peripheral nervous system. To our knowledge, the effect of lidocaine
      on the brain's functional response to pain has never been investigated. Here, we
      therefore characterized the effect of systemic lidocaine on the brain's response
      to innocuous and acute noxious stimulation in the rat using functional magnetic
      resonance imaging (fMRI). METHODS: Alpha-chloralose anesthetized rats underwent
      fMRI to quantify brain activation patterns in response to innocuous and noxious
      forepaw stimulation before and after IV administration of lidocaine. RESULTS:
      Innocuous forepaw stimulation elicited brain activation only in the contralateral
      primary somatosensory (S1) cortex. Acute noxious forepaw stimulation induced
      activation in additional brain areas associated with pain perception, including
      the secondary somatosensory cortex (S2), thalamus, insula and limbic regions.
      Lidocaine administered at IV doses of either 1 mg/kg, 4 mg/kg or 10 mg/kg did not
      abolish or diminish brain activation in response to innocuous or noxious
      stimulation. In fact, IV doses of 4 mg/kg and 10 mg/kg lidocaine enhanced S1 and
      S2 responses to acute nociceptive stimulation, increasing the activated cortical
      volume by 50%-60%. CONCLUSION: The analgesic action of systemic lidocaine in
      acute pain is not reflected in a straightforward interruption of pain-induced
      fMRI brain activation as has been observed with opioids. The enhancement of
      cortical fMRI responses to acute pain by lidocaine observed here has also been
      reported for cocaine. We recently showed that both lidocaine and cocaine
      increased intracellular calcium concentrations in cortex, suggesting that this
      pharmacological effect could account for the enhanced sensitivity to
      somatosensory stimulation. As our model only measured physiological acute pain,
      it will be important to also test the response of these same pathways to
      lidocaine in a model of neuropathic pain to further investigate lidocaine's
      analgesic mechanism of action.

PMID- 19095873
TI  - A randomized comparison of a modified intertendinous and classic posterior
      approach to popliteal sciatic nerve block.
AB  - INTRODUCTION: In this prospective randomized study, we compared a single
      injection modified intertendinous (n = 55) with the classic posterior (n = 54)
      popliteal sciatic nerve block for patients undergoing ankle/foot surgery.
      METHODS: Nerve stimulator-guided blocks were performed 7-8 cm (classic posterior)
      or 12-14 cm (modified intertendinous) above the popliteal crease. Levobupivacaine
      0.625% with epinephrine 1:300,000 (Chirocaine(R), Purdue Pharma, Stamford, CT),
      was injected in 5 mL aliquots to a total volume of 0.4 mL/kg (range, 25-35 mL).
      The needle position was considered acceptable if an evoked motor response of
      plantar flexion, inversion, eversion or a dorsiflexion of the ipsilateral foot
      was elicited at <or=0.4 mA. Complete block was defined as pinprick anesthesia and
      motor paralysis of the foot within 60 min. RESULTS: The median distance from the
      popliteal crease to the modified intertendinous site was 14.0 cm (interquartile
      range, 13.5-15 cm) compared to 7.5 cm (interquartile range 7.0-8.0 cm) for the
      classic posterior site (P < 0.01). Complete block was achieved in 44 of 55
      patients (81.5%) in the modified intertendinous compared to 39 of 54 patients
      (70.9%) in the classic posterior group (P = 0.26). Complete block frequency was
      greater with an evoked motor response of inversion 49 of 56 patients (87.5%) and
      plantar flexion 23 of 30 patients (76.7%) compared with dorsiflexion/eversion 11
      of 23 patients (47.8%) (P = 0.001). The median (95% CI) time (min) to complete
      block with an evoked motor response of inversion was 10 (0-22 min) for the
      modified intertendinous compared to 30 (4-56 min) with the classic posterior
      approach (P = 0.04). CONCLUSIONS: Potential advantages of the modified
      intertendinous approach include more rapid onset of anesthesia with an evoked
      motor response of inversion compared to a classic posterior popliteal sciatic
      nerve block.

PMID- 19095874
TI  - The influence of arm abduction on the anatomic relations of infraclavicular
      brachial plexus: an ultrasound study.
AB  - BACKGROUND: Distances from brachial plexus to the coracoid process and the pleura
      are critical for performing infraclavicular block. We evaluated the influence of
      arm abduction on the position of the neurovascular bundle relative to the skin,
      to the coracoid process and to the pleura using ultrasonography. METHODS: An
      ultrasound examination of the brachial plexus at the infraclavicular level was
      performed on 26 patients. Distances from the axillary artery to the skin, to the
      coracoid process and to the pleura were measured and noted with different degrees
      of arm abduction (0 degrees , 45 degrees , and 90 degrees ). Vertical
      infraclavicular brachial plexus block was then performed by means of nerve
      stimulation in 14 additional patients undergoing hand surgery. RESULTS: Under
      ultrasound examination, the distance from the axillary artery to the skin was
      found to be significantly less with arm abduction (0 degrees : 32 +/- 7 mm, 45
      degrees : 29 +/- 7 mm, 90 degrees : 25 +/- 5 mm, P < 0.05). The distance from the
      skin to the pleura was 47 +/- 5 mm with a medial deviation of 18 +/- 3 degrees
      and was not influenced by arm position. Brachial plexus was identified by nerve
      stimulation at a vertical depth of 41 +/- 7 mm from the skin. CONCLUSION:
      Abduction of the arm reduces the depth of the brachial plexus but does not change
      the position of the axillary artery relative to the coracoid process or the
      pleura. Ultrasonography may under-estimate the actual depth of the plexus.

PMID- 19095876
TI  - Migration of a thoracic epidural catheter into the intercostal space via the
      intervertebral foramen.
AB  - We describe a documented migration of a thoracic epidural catheter into the
      thoracic cage in a 5-wk-old with DiGeorge's syndrome and an uncorrected acyanotic
      Tetralogy of Fallot who underwent laparotomy for malrotation, gastric
      fundoplication, and gastrostomy tube insertion under combined general and
      epidural anesthesia. A 20-gauge stimulating catheter was inserted caudally and
      advanced cephalad to the thoracic level while applying a low electrical current
      (1-10 mA) to confirm epidural placement at approximately T5-6. Despite good pain
      control through the third postoperative day, using an epidural infusion of
      bupivacaine 0.1% at 1-1.2 mL/h, radiography demonstrated catheter migration into
      the seventh intercostal space.

PMID- 19095875
TI  - Tramadol as an adjuvant to lidocaine for axillary brachial plexus block.
AB  - BACKGROUND: In this prospective randomized study, we evaluated the effect of
      tramadol as an adjuvant to axillary block. METHODS: We studied 102 patients
      scheduled for hand surgery under axillary block with lidocaine 1.5% (epinephrine
      1/200,000) and the addition of either 4 mL saline (control group), 100 mg
      tramadol and 2 mL saline (TL group), or 200 mg tramadol (TH group). RESULTS:
      Onset time was longer in the TH group, 16 +/- 7 min (9 +/- 3 min in control
      group; P = 0.01). Sensory block and time for first rescue analgesia were
      significantly prolonged in the TH group compared with both TL and control groups
      (265 +/- 119 min vs 190 +/- 87 min vs 126 +/- 48 min; P = 0.018); (734 +/- 434
      min vs 573 +/- 516 min vs 375 +/- 316 min; P = 0.02). CONCLUSIONS: The benefit of
      block prolongation associated with the addition of 200 mg tramadol to lidocaine
      during axillary block is limited by the slow onset of the block.

PMID- 19095877
TI  - Do no harm.

PMID- 19095878
TI  - Research, not quality assurance.

PMID- 19095879
TI  - I appreciate the dialog between Drs. Anderson and Schonfeld and Murphy et al.

PMID- 19095880
TI  - Dixon and massey's method: the starting dose.

PMID- 19095881
TI  - Dexmedetomidine sedation (and cardiac perforation, pericardial tamponade, cardiac
      arrest, and cardiopulmonary resuscitation) leading to refractory cardiogenic
      shock.

PMID- 19095882
TI  - Sequential allocation method.

PMID- 19095883
TI  - Caution is necessary when dexmedetomidine is used off-label, especially when
      combined with other sedatives.

PMID- 19095884
TI  - Dexmedetomidine and refractory cardiogenic shock.

PMID- 19095885
TI  - Fospropofol assay issues and impact on pharmacokinetic and pharmacodynamic
      evaluation.

PMID- 19095886
TI  - Simplifying the noncardiac surgery evaluation pathway.

PMID- 19095887
TI  - Peripheral neuropathy following colonoscopy is not uncommon.

PMID- 19095888
TI  - Prevention of corneal abrasions in patients with autoimmune dry eyes.

PMID- 19095889
TI  - Alexandrite 755 nm laser-induced pulse oximetry dysfunction.

PMID- 19095891
TI  - ADHD and health services utilization in the national health interview survey.
AB  - OBJECTIVE: Describe the general health, comorbidities and health service use
      among U.S. children with ADHD. METHOD: The 2001 National Health Interview Survey
      (NHIS) contained the Strengths and Difficulties Questionnaire (SDQ; used to
      determine probable ADHD), data on medical problems, overall health, and health
      care utilization. RESULTS: Asthma was two and headaches were three times more
      prevalent, and overall health was significantly lower, among children with SDQ
      ADHD. Of children with SDQ ADHD, 45% saw a mental health professional in the past
      year and over half were not taking medication regularly. Urban residence, age (9
      13), higher family education, having health insurance, and having comorbid
      emotional problems were associated with mental health care utilization in
      children with SDQ AD/HD, while race, gender and family income were not
      associated. CONCLUSIONS: Children with SDQ AD/HD had more medical problems and
      were more likely to visit the emergency room. Treatment data suggest a problem
      with under-treatment of ADHD in the United States. Interventions should be
      targeted in rural areas, and among families with low education and without health
      insurance.

PMID- 19095890
TI  - Bonfils fiberscope: better preoxygenate rather than oxygenate!

PMID- 19095892
TI  - Effective methylphenidate treatment of an adult Aspergers Syndrome and a comorbid
      ADHD: a clinical investigation with fMRI.
AB  - OBJECTIVE: Aspergers Syndrome can present as comorbid with attention
      deficit/hyperactivity disorder (ADHD). Very few cases of the assessment and
      treatment of this comorbidity in adulthood are described in the research
      literature. METHOD: A 26-year-old patient as suffering from ADHD in combination
      with Aspergers Syndrome is diagnosed. Treatment is started with methylphenidate
      (MPH), and the patient's clinical response is observed, psychological tests
      concerning attention are analyzed, and a functional magnetic resonance imaging
      (fMRI) examination is performed during an attention-task. RESULTS: On the
      functional magnetic resonance imaging, a reduction of cerebral activity
      bilaterally in the parietal lobe under the influence of MPH is detected.
      CONCLUSION: Besides the neurophysiological findings, this case reports the
      complex impairment caused by the combination of AD/HD with Aspergers Syndrome and
      the broad social and behavioral benefits of treatment with MPH for this
      comorbidity.

PMID- 19095894
TI  - The experiences of socioeconomically disadvantaged postpartum women in the first
      4 weeks at home.
AB  - We used a qualitative descriptive approach to explore and describe the situated
      experiences of socioeconomically disadvantaged (SED) postpartum women in the
      first 4 weeks after hospital discharge. Qualitative content analysis was used to
      analyze the data from in-depth interviews with 24 SED postpartum women. Two
      intertwining, overarching themes emerged: (a) the ongoing burden of their day-to
      day lives, with subthemes of poverty and material deprivation, stigmatization
      through living publicly examined lives, and precarious social support; and (b)
      the ongoing struggles to adjust to changes that came with the baby's arrival,
      with subthemes of "the first weeks were hard," "feeling out of control," "absence
      of help at home," "complex relationship with the baby's father," and "health and
      well-being." Knowledge of SED women's situated experiences is vital to the
      development of health policies and services that will truly meet their needs.

PMID- 19095895
TI  - A meta-analysis examining clinical test utility for assessing superior labral
      anterior posterior lesions.
AB  - BACKGROUND: The reported accuracy of clinical tests for superior labral anterior
      posterior lesions is extremely variable. Pooling results from multiple studies of
      higher quality is necessary to establish the best clinical tests to use.
      HYPOTHESIS: Certain clinical tests are superior to others for diagnosing the
      presence or absence of a superior labral anterior posterior lesion. STUDY DESIGN:
      Meta-analysis. METHODS: A literature search of MEDLINE (1966-2007), CINAHL (1982
      2007), and BIOSIS (1995-2007) was performed for (labrum OR labral OR SLAP OR
      Bankart) AND (shoulder OR shoulder joint OR glenoid) AND (specificity OR
      sensitivity AND specificity). Identified articles were reviewed for inclusion
      criteria. Sensitivity and specificity values were recorded from each study and
      used for meta-analysis. RESULTS: Six of 198 identified studies satisfied the
      eligibility criteria. Active compression, anterior slide, crank, and Speed tests
      were analyzed using receiver operating characteristic curves. The accuracy of the
      anterior slide test was significantly inferior to that of the active compression,
      crank, and Speed tests. There was no significant difference in test accuracy
      found among active compression, crank, and Speed tests. Between studies,
      methodological scores did not significantly affect sensitivity and specificity
      values. CONCLUSION: The anterior slide test is a poor test for detecting the
      presence of a labral lesion in the shoulder. Active compression, crank, and Speed
      tests are more optimal choices. Clinicians should choose the active compression
      test first, crank second, and Speed test third when a labral lesion is suspected.

PMID- 19095896
TI  - Foraminiferal isotope evidence of reduced nitrogen fixation in the ice age
      Atlantic Ocean.
AB  - Fixed nitrogen (N) is a limiting nutrient for algae in the low-latitude ocean,
      and its oceanic inventory may have been higher during ice ages, thus helping to
      lower atmospheric CO2 during those intervals. In organic matter within planktonic
      foraminifera shells in Caribbean Sea sediments, we found that the 15N/14N ratio
      from the last ice age is higher than that from the current interglacial,
      indicating a higher nitrate 15N/14N ratio in the Caribbean thermocline. This
      change and other species-specific differences are best explained by less N
      fixation in the Atlantic during the last ice age. The fixation decrease was most
      likely a response to a known ice age reduction in ocean N loss, and it would have
      worked to balance the ocean N budget and to curb ice age-interglacial change in
      the N inventory.

PMID- 19095897
TI  - Rapid membrane disruption by a perforin-like protein facilitates parasite exit
      from host cells.
AB  - Perforin-like proteins are expressed by many bacterial and protozoan pathogens,
      yet little is known about their function or mode of action. Here, we describe
      Toxoplasma perforin-like protein 1 (TgPLP1), a secreted perforin-like protein of
      the intracellular protozoan pathogen Toxoplasma gondii that displays structural
      features necessary for pore formation. After intracellular growth, TgPLP1
      deficient parasites failed to exit normally, resulting in entrapment within host
      cells. We show that this defect is due to an inability to rapidly permeabilize
      the parasitophorous vacuole membrane and host plasma membrane during exit. TgPLP1
      ablation had little effect on growth in culture but resulted in a reduction
      greater than five orders of magnitude of acute virulence in mice. Perforin-like
      proteins from other intracellular pathogens may play a similar role in microbial
      egress and virulence.

PMID- 19095899
TI  - Electron cryomicroscopy of E. coli reveals filament bundles involved in plasmid
      DNA segregation.
AB  - Bipolar elongation of filaments of the bacterial actin homolog ParM drives
      movement of newly replicated plasmid DNA to opposite poles of a bacterial cell.
      We used a combination of vitreous sectioning and electron cryotomography to study
      this DNA partitioning system directly in native, frozen cells. The diffraction
      patterns from overexpressed ParM bundles in electron cryotomographic
      reconstructions were used to unambiguously identify ParM filaments in Escherichia
      coli cells. Using a low-copy number plasmid encoding components required for
      partitioning, we observed small bundles of three to five intracellular ParM
      filaments that were situated close to the edge of the nucleoid. We propose that
      this may indicate the capture of plasmid DNA within the periphery of this loosely
      defined, chromosome-containing region.

PMID- 19095898
TI  - Glucosinolate metabolites required for an Arabidopsis innate immune response.
AB  - The perception of pathogen or microbe-associated molecular pattern molecules by
      plants triggers a basal defense response analogous to animal innate immunity and
      is defined partly by the deposition of the glucan polymer callose at the cell
      wall at the site of pathogen contact. Transcriptional and metabolic profiling in
      Arabidopsis mutants, coupled with the monitoring of pathogen-triggered callose
      deposition, have identified major roles in pathogen response for the plant
      hormone ethylene and the secondary metabolite 4-methoxy-indol-3
      ylmethylglucosinolate. Two genes, PEN2 and PEN3, are also necessary for
      resistance to pathogens and are required for both callose deposition and
      glucosinolate activation, suggesting that the pathogen-triggered callose response
      is required for resistance to microbial pathogens. Our study shows that well
      studied plant metabolites, previously identified as important in avoiding damage
      by herbivores, are also required as a component of the plant defense response
      against microbial pathogens.

PMID- 19095900
TI  - A glucosinolate metabolism pathway in living plant cells mediates broad-spectrum
      antifungal defense.
AB  - Selection pressure exerted by insects and microorganisms shapes the diversity of
      plant secondary metabolites. We identified a metabolic pathway for
      glucosinolates, known insect deterrents, that differs from the pathway activated
      by chewing insects. This pathway is active in living plant cells, may contribute
      to glucosinolate turnover, and has been recruited for broad-spectrum antifungal
      defense responses. The Arabidopsis CYP81F2 gene encodes a P450 monooxygenase that
      is essential for the pathogen-induced accumulation of 4-methoxyindol-3
      ylmethylglucosinolate, which in turn is activated by the atypical PEN2 myrosinase
      (a type of beta-thioglucoside glucohydrolase) for antifungal defense. We propose
      that reiterated enzymatic cycles, controlling the generation of toxic molecules
      and their detoxification, enable the recruitment of glucosinolates in defense
      responses.

PMID- 19095901
TI  - Celebrating a year of Science.

PMID- 19095902
TI  - Breakthrough of the year. Reprogramming Cells.

PMID- 19095903
TI  - Video: reprogramming cells.
AB  - This video introduction to Science's year-end special issue features Shinya
      Yamanaka of Kyoto University, George Daley of Harvard University, and Science's
      Gretchen Vogel reviewing some of the work that led studies in reprogramming cells
      to be tagged the top scientific story for 2008.

PMID- 19095904
TI  - Breakthrough of the year. The runners-up.

PMID- 19095905
TI  - Phenomenon of the year. European big science.

PMID- 19095906
TI  - Breakthrough of the year. Scorecard.

PMID- 19095908
TI  - Breakthrough of the year. Areas to watch.

PMID- 19095907
TI  - Breakdown of the year. Financial meltdown.

PMID- 19095909
TI  - The transition. Nobelist gets energy portfolio, raising hopes and expectations.

PMID- 19095910
TI  - The transition. Obama's choice to direct EPA is applauded.

PMID- 19095911
TI  - Malaria. Signs of drug resistance rattle experts, trigger bold plan.

PMID- 19095912
TI  - Nuclear physics. DOE picks Michigan State lab for rare-isotope accelerator.

PMID- 19095913
TI  - Endangered species. Rangers assess toll of Congo conflict on threatened mountain
      gorillas.

PMID- 19095914
TI  - Science policy. Report faults U.S. strategy for nanotoxicology research.

PMID- 19095916
TI  - Planetary science. Europa vs. Titan.

PMID- 19095917
TI  - Zack Booth Simpson profile. An artist develops a new image--with aid of bacteria.

PMID- 19095918
TI  - Materials Research Society fall meeting. Shortfalls in electron production dim
      hopes for MEG solar cells.

PMID- 19095919
TI  - Materials Research Society fall meeting. Protein chip promises cheaper
      diagnostics.

PMID- 19095920
TI  - Materials Research Society fall meeting. Graphene recipe yields carbon
      cornucopia.

PMID- 19095921
TI  - Marine mammals. Does 'junk food' threaten marine predators in northern seas?

PMID- 19095922
TI  - Making waves with the Clean Water Act.

PMID- 19095923
TI  - The state of global hunger.

PMID- 19095924
TI  - Bird brains key to the functions of sleep.

PMID- 19095925
TI  - Old seeds coming in from the cold.

PMID- 19095926
TI  - Comment on "Declining wild salmon populations in relation to parasites from farm
      salmon".
AB  - Krkosek et al. (Reports, 14 December 2007, p. 1772) claimed that sea lice spread
      from salmon farms placed wild pink salmon populations "on a trajectory toward
      rapid local extinction." Their prediction is inconsistent with observed pink
      salmon returns and overstates the risks from sea lice and salmon farming.

PMID- 19095927
TI  - The pipeline. Science faculty with education specialties.

PMID- 19095928
TI  - Research funding. Politics and funding in the U.S. public biomedical R&D system.

PMID- 19095929
TI  - Evolution. Who's your daddy?

PMID- 19095930
TI  - Computer science. The ethical frontiers of robotics.

PMID- 19095931
TI  - Materials science. Now you see them.

PMID- 19095932
TI  - Developmental biology. From genetic association to genetic switch.

PMID- 19095933
TI  - Transcription. Gene expression--where to start?

PMID- 19095934
TI  - Nuclear reprogramming in cells.
AB  - Nuclear reprogramming describes a switch in gene expression of one kind of cell
      to that of another unrelated cell type. Early studies in frog cloning provided
      some of the first experimental evidence for reprogramming. Subsequent procedures
      included mammalian somatic cell nuclear transfer, cell fusion, induction of
      pluripotency by ectopic gene expression, and direct reprogramming. Through these
      methods it becomes possible to derive one kind of specialized cell (such as a
      brain cell) from another, more accessible, tissue (such as skin) in the same
      individual. This has potential applications for cell replacement without the
      immunosuppression treatments that are required when cells are transferred between
      genetically different individuals. This article provides some background to this
      field, a discussion of mechanisms and efficiency, and comments on prospects for
      future nuclear reprogramming research.

PMID- 19095935
TI  - Matching glass-forming ability with the density of the amorphous phase.
AB  - The density of the amorphous phase of metals is generally thought to be related
      to glass formation, but this correlation has not been demonstrated experimentally
      to date. In this work, systematic deflection measurements using microcantilevers
      and a combinatorial deposition method show a correlation between glass-forming
      ability and the density change upon crystallization over a broad compositional
      range in the copper-zirconium binary system. Distinct peaks in the density of the
      amorphous phase were found to correlate with specific maxima in the critical
      thickness for glass formation. Our findings provide quantitative data for the
      development of structural models of liquids that are readily quenched to the
      amorphous state. The experimental method developed in this work can facilitate
      the search for new glass-forming alloys.

PMID- 19095936
TI  - Stable prenucleation calcium carbonate clusters.
AB  - Calcium carbonate forms scales, geological deposits, biominerals, and ocean
      sediments. Huge amounts of carbon dioxide are retained as carbonate ions, and
      calcium ions represent a major contribution to water hardness. Despite its
      relevance, little is known about the precipitation mechanism of calcium
      carbonate, and specified complex crystal structures challenge the classical view
      on nucleation considering the formation of metastable ion clusters. We
      demonstrate that dissolved calcium carbonate in fact contains stable
      prenucleation ion clusters forming even in undersaturated solution. The cluster
      formation can be characterized by means of equilibrium thermodynamics, applying a
      multiple-binding model, which allows for structural preformation. Stable clusters
      are the relevant species in calcium carbonate nucleation. Such mechanisms may
      also be important for the crystallization of other minerals.

PMID- 19095937
TI  - Shock-wave exploration of the high-pressure phases of carbon.
AB  - The high-energy density behavior of carbon, particularly in the vicinity of the
      melt boundary, is of broad scientific interest and of particular interest to
      those studying planetary astrophysics and inertial confinement fusion. Previous
      experimental data in the several hundred gigapascal pressure range, particularly
      near the melt boundary, have only been able to provide data with accuracy capable
      of qualitative comparison with theory. Here we present shock-wave experiments on
      carbon (using a magnetically driven flyer-plate technique with an order of
      magnitude improvement in accuracy) that enable quantitative comparison with
      theory. This work provides evidence for the existence of a diamond-bc8-liquid
      triple point on the melt boundary.

PMID- 19095938
TI  - Avian paternal care had dinosaur origin.
AB  - The repeated discovery of adult dinosaurs in close association with egg clutches
      leads to speculation over the type and extent of care exhibited by these extinct
      animals for their eggs and young. To assess parental care in Cretaceous
      troodontid and oviraptorid dinosaurs, we examined clutch volume and the bone
      histology of brooding adults. In comparison to four archosaur care regressions,
      the relatively large clutch volumes of Troodon, Oviraptor, and Citipati scale
      most closely with a bird-paternal care model. Clutch-associated adults lack the
      maternal and reproductively associated histologic features common to extant
      archosaurs. Large clutch volumes and a suite of reproductive features shared only
      with birds favor paternal care, possibly within a polygamous mating system.
      Paternal care in both troodontids and oviraptorids indicates that this care
      system evolved before the emergence of birds and represents birds' ancestral
      condition. In extant birds and over most adult sizes, paternal and biparental
      care correspond to the largest and smallest relative clutch volumes,
      respectively.

PMID- 19095939
TI  - Orbital identification of carbonate-bearing rocks on Mars.
AB  - Geochemical models for Mars predict carbonate formation during aqueous
      alteration. Carbonate-bearing rocks had not previously been detected on Mars'
      surface, but Mars Reconnaissance Orbiter mapping reveals a regional rock layer
      with near-infrared spectral characteristics that are consistent with the presence
      of magnesium carbonate in the Nili Fossae region. The carbonate is closely
      associated with both phyllosilicate-bearing and olivine-rich rock units and
      probably formed during the Noachian or early Hesperian era from the alteration of
      olivine by either hydrothermal fluids or near-surface water. The presence of
      carbonate as well as accompanying clays suggests that waters were neutral to
      alkaline at the time of its formation and that acidic weathering, proposed to be
      characteristic of Hesperian Mars, did not destroy these carbonates and thus did
      not dominate all aqueous environments.

PMID- 19095940
TI  - The circadian clock in Arabidopsis roots is a simplified slave version of the
      clock in shoots.
AB  - The circadian oscillator in eukaryotes consists of several interlocking feedback
      loops through which the expression of clock genes is controlled. It is generally
      assumed that all plant cells contain essentially identical and cell-autonomous
      multiloop clocks. Here, we show that the circadian clock in the roots of mature
      Arabidopsis plants differs markedly from that in the shoots and that the root
      clock is synchronized by a photosynthesis-related signal from the shoot. Two of
      the feedback loops of the plant circadian clock are disengaged in roots, because
      two key clock components, the transcription factors CCA1 and LHY, are able to
      inhibit gene expression in shoots but not in roots. Thus, the plant clock is
      organ-specific but not organ-autonomous.

PMID- 19095941
TI  - A conserved molecular framework for compound leaf development.
AB  - Diversity in leaf shape is produced by alterations of the margin: for example,
      deep dissection leads to leaflet formation and less-pronounced incision results
      in serrations or lobes. By combining gene silencing and mutant analyses in four
      distantly related eudicot species, we show that reducing the function of NAM/CUC
      boundary genes (NO APICAL MERISTEM and CUP-SHAPED COTYLEDON) leads to a
      suppression of all marginal outgrowths and to fewer and fused leaflets. We
      propose that NAM/CUC genes promote formation of a boundary domain that delimits
      leaflets. This domain has a dual role promoting leaflet separation locally and
      leaflet formation at distance. In this manner, boundaries of compound leaves
      resemble boundaries functioning during animal development.

PMID- 19095942
TI  - CRISPR interference limits horizontal gene transfer in staphylococci by targeting
      DNA.
AB  - Horizontal gene transfer (HGT) in bacteria and archaea occurs through phage
      transduction, transformation, or conjugation, and the latter is particularly
      important for the spread of antibiotic resistance. Clustered, regularly
      interspaced, short palindromic repeat (CRISPR) loci confer sequence-directed
      immunity against phages. A clinical isolate of Staphylococcus epidermidis harbors
      a CRISPR spacer that matches the nickase gene present in nearly all
      staphylococcal conjugative plasmids. Here we show that CRISPR interference
      prevents conjugation and plasmid transformation in S. epidermidis. Insertion of a
      self-splicing intron into nickase blocks interference despite the reconstitution
      of the target sequence in the spliced mRNA, which indicates that the interference
      machinery targets DNA directly. We conclude that CRISPR loci counteract multiple
      routes of HGT and can limit the spread of antibiotic resistance in pathogenic
      bacteria.

PMID- 19095943
TI  - Label-free biomedical imaging with high sensitivity by stimulated Raman
      scattering microscopy.
AB  - Label-free chemical contrast is highly desirable in biomedical imaging.
      Spontaneous Raman microscopy provides specific vibrational signatures of chemical
      bonds, but is often hindered by low sensitivity. Here we report a three
      dimensional multiphoton vibrational imaging technique based on stimulated Raman
      scattering (SRS). The sensitivity of SRS imaging is significantly greater than
      that of spontaneous Raman microscopy, which is achieved by implementing high
      frequency (megahertz) phase-sensitive detection. SRS microscopy has a major
      advantage over previous coherent Raman techniques in that it offers background
      free and readily interpretable chemical contrast. We show a variety of biomedical
      applications, such as differentiating distributions of omega-3 fatty acids and
      saturated lipids in living cells, imaging of brain and skin tissues based on
      intrinsic lipid contrast, and monitoring drug delivery through the epidermis.

PMID- 19095944
TI  - Leukemic cells create bone marrow niches that disrupt the behavior of normal
      hematopoietic progenitor cells.
AB  - The host tissue microenvironment influences malignant cell proliferation and
      metastasis, but little is known about how tumor-induced changes in the
      microenvironment affect benign cellular ecosystems. Applying dynamic in vivo
      imaging to a mouse model, we show that leukemic cell growth disrupts normal
      hematopoietic progenitor cell (HPC) bone marrow niches and creates abnormal
      microenvironments that sequester transplanted human CD34+ (HPC-enriched) cells.
      CD34+ cells in leukemic mice declined in number over time and failed to mobilize
      into the peripheral circulation in response to cytokine stimulation.
      Neutralization of stem cell factor (SCF) secreted by leukemic cells inhibited
      CD34+ cell migration into malignant niches, normalized CD34+ cell numbers, and
      restored CD34+ cell mobilization in leukemic mice. These data suggest that the
      tumor microenvironment causes HPC dysfunction by usurping normal HPC niches and
      that therapeutic inhibition of HPC interaction with tumor niches may help
      maintain normal progenitor cell function in the setting of malignancy.

PMID- 19095945
TI  - Representation of geometric borders in the entorhinal cortex.
AB  - We report the existence of an entorhinal cell type that fires when an animal is
      close to the borders of the proximal environment. The orientation-specific edge
      apposing activity of these "border cells" is maintained when the environment is
      stretched and during testing in enclosures of different size and shape in
      different rooms. Border cells are relatively sparse, making up less than 10% of
      the local cell population, but can be found in all layers of the medial
      entorhinal cortex as well as the adjacent parasubiculum, often intermingled with
      head-direction cells and grid cells. Border cells may be instrumental in planning
      trajectories and anchoring grid fields and place fields to a geometric reference
      frame.

PMID- 19095947
TI  - Elevated expressions of 15-lipoxygenase and lipoxin A4 in children with acute
      poststreptococcal glomerulonephritis.
AB  - Anti-inflammatory effects of the 15-lipoxygenase (15-LO) derivatives lipoxin A(4)
      (LXA(4)) and 15-S-hydroxyeicosatetraenoic acid (15-S-HETE) have been documented
      in many experimental models of acute inflammation. However, the expression levels
      of 15-LO and its products in human renal diseases remain unknown. This study
      investigated the expression levels of LXA(4), leukotriene B(4) (LTB(4)), and 15
      LO in leukocytes and glomeruli obtained from 22 children with acute
      poststreptococcal glomerulonephritis (APSGN), and determined the modulatory
      effects of both 15-S-HETE and LXA(4) on LTB(4) synthesis in leukocytes and LTB(4)
      evoked chemotaxis of polymorphonuclear leukocytes (PMNs) obtained from children
      during the first 3 days after onset of APSGN. Expression levels of both LXA(4)
      and 15-LO in leukocytes and glomeruli were up-regulated during the acute phase of
      disease, further peaking between days 10 and 14, and remained increased after 6
      to 8 weeks of APSGN onset. In contrast, blood and urinary levels of LTB(4) as
      well as the number of glomerular PMNs peaked during the acute phase of disease
      and then decreased during the resolution phase. Administration of both 15-S-HETE
      and LXA(4) in vitro inhibited LTB(4)-induced chemotaxis of PMNs and production of
      LTB(4) from leukocytes obtained from patients with APSGN. The current study
      provides further support for an anti-inflammatory role for 15-LO products in
      human nephritis through both antagonism and inhibition of leukotriene synthesis
      and its biological activity.

PMID- 19095948
TI  - Activin C antagonizes activin A in vitro and overexpression leads to pathologies
      in vivo.
AB  - Activin A is a potent growth and differentiation factor whose synthesis and
      bioactivity are tightly regulated. Both follistatin binding and inhibin subunit
      heterodimerization block access to the activin receptor and/or receptor
      activation. We postulated that the activin-beta(C) subunit provides another
      mechanism regulating activin bioactivity. To test our hypothesis, we examined the
      biological effects of activin C and produced mice that overexpress activin
      beta(C). Activin C reduced activin A bioactivity in vitro; in LNCaP cells,
      activin C abrogated both activin A-induced Smad signaling and growth inhibition,
      and in LbetaT2 cells, activin C antagonized activin A-mediated activity of an
      follicle-stimulating hormone-beta promoter. Transgenic mice that overexpress
      activin-betaC exhibited disease in testis, liver, and prostate. Male infertility
      was caused by both reduced sperm production and impaired sperm motility. The
      livers of the transgenic mice were enlarged because of an imbalance between
      hepatocyte proliferation and apoptosis. Transgenic prostates showed evidence of
      hypertrophy and epithelial cell hyperplasia. Additionally, there was decreased
      evidence of nuclear Smad-2 localization in the testis, liver, and prostate,
      indicating that overexpression of activin-beta(C) antagonized Smad signaling in
      vivo. Underlying the significance of these findings, human testis, liver, and
      prostate cancers expressed increased activin-betaC immunoreactivity. This study
      provides evidence that activin-beta(C) is an antagonist of activin A and supplies
      an impetus to examine its role in development and disease.

PMID- 19095949
TI  - Neuroprotection and remyelination after autoimmune demyelination in mice that
      inducibly overexpress CXCL1.
AB  - In rodents, the chemokine CXCL1 both induces the proliferation and inhibits the
      migration of oligodendrocyte precursor cells. We previously reported that in
      multiple sclerosis, the same chemokine is expressed by hypertrophic astrocytes,
      which associate with oligodendrocytes that express the receptor CXCR2. To
      investigate whether chemokines influence repair after autoimmune demyelination,
      we generated GFAP-rtTA x beta-Gal-TRE-CXCL1 double-transgenic (Tg) mice that
      inducibly overexpress CXCL1 under the control of the astrocyte-specific gene,
      glial fibrillary acidic protein. Experimental autoimmune encephalomyelitis, an
      animal model of multiple sclerosis, was induced in these animals (and controls)
      by the subcutaneous injection of myelin oligodendrocyte glycoprotein, and after
      disease onset, CXCL1 production was initiated by the intraperitoneal injection of
      doxycycline. Double-Tg animals displayed a milder course of disease compared with
      both single (CXCL1 or glial fibrillary acidic protein)-Tg and wild-type controls.
      Pathologies were similar in all groups during the acute stage of disease. During
      the chronic disease phase, both inflammation and demyelination were diminished in
      double-Tg mice and Wallerian degeneration was markedly decreased. Remyelination
      was strikingly more prominent in double-Tg mice, together with an apparent
      increased number of oligodendrocytes. Moreover, cell proliferation, indicated by
      BrdU incorporation within the central nervous system, was more widespread in the
      white matter of double-Tg animals. These findings suggest a neuroprotective role
      for CXCL1 during the course of autoimmune demyelination.

PMID- 19095950
TI  - Irs2 inactivation suppresses tumor progression in Pten+/- mice.
AB  - Mutations in the phosphatase and tensin homologue (PTEN)/phosphatidylinositol-3
      kinase-alpha (PI3K) signaling pathway are frequently found in human cancer. In
      addition, Pten(+/-) mice develop tumors in multiple organs because of the
      activation of the PI3K signaling cascade. Because activation of PI3K signaling
      leads to feedback inhibition of insulin receptor substrate-2 (IRS2) expression,
      an upstream activator of PI3K, we therefore anticipated that IRS2 expression
      would be low in tumors that lack PTEN. Surprisingly, however, an elevation of
      IRS2 was often detected in tumor samples in which PTEN levels were compromised.
      To determine the potential contribution of Irs2 to tumor progression, Pten(+/-)
      mice were crossed with Irs2(+/-) mice. Deletion of Irs2 did not affect the
      initiation of neoplasia found in Pten(+/-) mice but suppressed cancer cell
      growth, proliferation, and invasion through the basement membrane. Deletion of
      Irs2 also attenuated the expression of Myc in prostatic intraepithelial neoplasia
      in Pten(+/-) mice. In addition, the expression levels of IRS2 and MYC were highly
      correlated in human prostate cancer, and IRS2 could stimulate MYC expression in
      cultured cells. Our findings provide evidence that the PI3K-activating adaptor
      Irs2 contributes to tumor progression in Pten(+/-) mice by stimulating both Myc
      and DNA synthesis.

PMID- 19095951
TI  - Expression pattern and subcellular localization of human papillomavirus minor
      capsid protein L2.
AB  - The expression pattern of human papillomavirus (HPV) capsid antigen L2 is poorly
      described, and the significance of its localization with both promyelocytic
      leukemia protein (PML) and Daxx in a subnuclear domain, nuclear domain 10 (ND
      10), when ectopically expressed in tissue culture cells is controversial. To
      address whether ND-10 localization of L2 occurs in natural cervical lesions, we
      used a HPV16 and HPV18 L2-specific monoclonal antibody (RG-1), in addition to
      rabbit antiserum to HPV6 L2, to localize L2. Immunohistochemical staining with RG
      1 produced diffuse staining in the nuclei of some cells located within the
      superficial epithelial layers in eight of nine cases of HPV16/18(+) cervical
      intraepithelial neoplasia grade 1 (CIN1); however, no staining was observed in
      HPV16/18(+) high-grade CIN (0 of 8 cases), normal cervical epithelium (0 of 20
      cases), cervical squamous cell carcinoma (0 of 102 cases), adenocarcinoma (0 of
      51 cases), or adenosquamous carcinoma (0 of 6 cases). HPV16/18(+) cervical
      lesions that express L2 exhibit higher HPV16/18 genome copies per cell compared
      with those that do not positively stain with RG-1 (P = 0.04). RG-1 staining of
      HeLa cells transfected with L2 expression constructs was frequently concentrated
      in the ND-10, particularly in cells expressing high levels of L2, and co
      localized with the cellular markers of ND-10, PML, and Daxx. In contrast, L2 was
      primarily diffuse within the nucleus and distinct from ND-10 as defined by PML
      immunofluorescent staining in CIN lesions, condylomata, and HPV16-transduced
      organotypic cultures.

PMID- 19095952
TI  - Valproate attenuates accelerated atherosclerosis in hyperglycemic apoE-deficient
      mice: evidence in support of a role for endoplasmic reticulum stress and glycogen
      synthase kinase-3 in lesion development and hepatic steatosis.
AB  - We have previously shown that glucosamine promotes endoplasmic reticulum (ER)
      stress in vascular cells leading to both inflammation and lipid accumulation--the
      hallmark features of atherosclerosis. Pretreatment with glycogen synthase kinase
      (GSK)-3 inhibitors protects cultured cells from ER stress-induced dysfunction.
      Here we evaluate the potential role of GSK-3 on the pro-atherogenic effects of
      hyperglycemia and ER stress. We show that GSK-3-deficient mouse embryonic
      fibroblasts do not accumulate unesterified cholesterol under conditions of ER
      stress. Furthermore, GSK-3 inhibitors, including valproate, attenuate ER stress
      induced unesterified cholesterol accumulation in wild-type mouse embryonic
      fibroblasts. In vivo we show that hyperglycemic apoE-deficient mice have
      accelerated atherogenesis at the aortic root compared with normoglycemic control
      mice. Mice fed a diet supplemented with 625 mg/kg valproate have significantly
      reduced lesion volume relative to nonsupplemented controls. Valproate
      supplementation has no apparent effect on the plasma levels of either glucose or
      lipids or on the expression of diagnostic markers of ER stress in the lesion.
      Significant reductions were observed in total hepatic lipids (>50.4%) and hepatic
      GSK-3beta activity (>55.8%) in mice fed the valproate diet. In conclusion,
      dietary supplementation with low levels of valproate significantly attenuates
      atherogenesis in hyperglycemic apoE-deficient mice. The in vivo anti-atherogenic
      effects of valproate are consistent with its ability to inhibit GSK-3 and
      interfere with pro-atherogenic ER stress signaling pathways in vitro.

PMID- 19095953
TI  - CD83+CCR7- dendritic cells accumulate in the subepithelial dome and internalize
      translocated Escherichia coli HB101 in the Peyer's patches of ileal Crohn's
      disease.
AB  - Recurrent Crohn's disease originates with small erosions in the follicle
      associated epithelium overlying the Peyer's patches. Animal studies have
      illustrated mucosal immune regulation by dendritic cells located in the
      subepithelial dome. The aim of this study was to characterize the dendritic cells
      at this specific site in patients with Crohn's disease. Ileal tissues were
      obtained after surgery performed on Crohn's patients; ileal samples from
      noninflammatory bowel disease and ulcerative colitis served as standard and
      inflammatory controls, respectively. Flow cytometry of isolated intestinal
      mononuclear cells showed a larger subset of dendritic cells in Crohn's samples
      compared with controls. This finding was corroborated by confocal microscopy,
      showing enhanced infiltrates of cells positive for the dendritic cell markers, DC
      SIGN(+) and CD83(+), in the subepithelial dome. Moreover, the CD83(+) cells in
      Crohn's tissues showed reduced expression of the lymph node migratory receptor,
      CCR7, possibly contributing to the high numbers of dendritic cells. After
      exposure to nonpathogenic Escherichia coli in Ussing chambers, dendritic cells in
      the subepithelial dome of Crohn's disease demonstrated increased co-localization
      with translocated bacteria. Immunohistochemical results revealed that DC-SIGN(+)
      cells in Crohn's tissues were found to express toll-like receptor 4 and produce
      tumor necrosis factor-alpha. In conclusion, nonmigrating dendritic cells that
      accumulate in the subepithelial dome and internalize nonpathogenic bacteria may
      be important for the onset and perpetuation of mucosal inflammation in Crohn's
      disease.

PMID- 19095954
TI  - The Krebs cycle and mitochondrial mass are early victims of endothelial
      dysfunction: proteomic approach.
AB  - Endothelial cell dysfunction is associated with bioavailable nitric oxide
      deficiency and an excessive generation of reactive oxygen species. We modeled
      this condition by chronically inhibiting nitric oxide generation with subpressor
      doses of N(G)-monomethyl-L-arginine (L-NMMA) in C57B6 and Tie-2/green fluorescent
      protein mouse strains. L-NMMA-treated mice exhibited a slight reduction in
      vasorelaxation ability, as well as detectable abnormalities in soluble adhesion
      molecules (soluble intercellular adhesion molecule-1 and vascular cellular
      adhesion molecule-1, and matrix metalloproteinase 9), which represent surrogate
      indicators of endothelial dysfunction. Proteomic analysis of the isolated
      microvasculature using 2-dimensional gel electrophoresis and matrix-assisted
      laser desorption/ionization time-of-flight mass spectroscopy revealed abnormal
      expression of a cluster of mitochondrial enzymes, which was confirmed using
      immunodetection. Aconitase-2 and enoyl-CoA-hydratase-1 expression levels were
      decreased in L-NMMA-treated animals; this phenotype was absent in nitric oxide
      synthase-1 and -3 knockout mice. Depletion of aconitase-2 and enoyl-CoA-hydratase
      1 resulted in the inhibition of the Krebs cycle and enhanced pyruvate shunting
      toward the glycolytic pathway. To assess mitochondrial mass in vivo, co
      localization of green fluorescent protein and MitoTracker fluorescence was
      detected by intravital microscopy. Quantitative analysis of fluorescence
      intensity showed that L-NMMA-treated animals exhibited lower fluorescence of
      MitoTracker in microvascular endothelia as a result of reduced mitochondrial
      mass. These findings provide conclusive and unbiased evidence that
      mitochondriopathy represents an early manifestation of endothelial dysfunction,
      shifting cell metabolism toward "metabolic hypoxia" through the selective
      depletion of both aconitase-2 and enoyl-CoA-hydratase-1. These findings may
      contribute to an early preclinical diagnosis of endothelial dysfunction.

PMID- 19095955
TI  - The effects of AGEing on diet.

PMID- 19095957
TI  - Functional and ultrastructural analysis of annexin A1 and its receptor in
      extravasating neutrophils during acute inflammation.
AB  - The purpose of this study was twofold: to reveal cellular events associated with
      the protective role of endogenous annexin A1 (AnxA1) in inflammation and to
      highlight the potential involvement of members of the formyl peptide receptor
      (Fpr) family in this process. We found that wild-type, AnxA1-null, and Fpr1-null
      mice all displayed an intense neutrophil recruitment into the peritoneal cavity
      as assessed 4 hours after carrageenin injection, and that this recruitment was
      most pronounced in AnxA1-null mice. In addition, this cell influx could be
      inhibited by the AnxA1 pharmacophore peptide, Ac2-26, in wild-type, AnxA1-null,
      and Fpr1-null mice, but was restored when co-treated with the pan-receptor
      antagonist Boc2. Using the LacZ gene reporter assay, an enhancement of AnxA1 gene
      promoter activity in extravasated neutrophils was evident in AnxA1-null mice;
      again this response was reduced after peptide treatment. The lack of functional
      involvement of Fpr1 prompted us to monitor the structurally related receptor
      Fpr2. We report, for the first time, the ultrastructural immunocytochemical co
      localization of Fpr2 with AnxA1 in neutrophils that migrate into the mesenteric
      microcirculation and extravasate into the peritoneal fluid. Collectively, these
      data provide in vivo support to the hypothesis that endogenous AnxA1 is an
      essential effector of endogenous anti-inflammation and provide an ultrastructural
      indication that this mediator interacts with Fpr2 in murine neutrophils. We
      believe that these findings could significantly affect the development of novel
      therapeutics, which are modeled after the anti-migratory actions of AnxA1.

PMID- 19095956
TI  - WNT/beta-catenin signaling is involved in regulation of osteoclast
      differentiation by human immunodeficiency virus protease inhibitor ritonavir:
      relationship to human immunodeficiency virus-linked bone mineral loss.
AB  - Untreated human immunodeficiency virus (HIV) infection is accompanied by reduced
      bone mineral density, which appears to be exacerbated by certain HIV protease
      inhibitors (PIs). The mechanisms leading to this apparent paradox, however,
      remain unclear. We have previously shown that, the HIV envelope glycoprotein
      gp120 used at levels similar those in plasmas of untreated HIV(+) patients,
      induced expression of the osteoclast (OC) differentiation factor RANKL in CD4+ T
      cells. In addition, the HIV PI ritonavir abrogated the interferon-gamma-mediated
      degradation of the RANKL nuclear adapter protein TRAF6, a physiological block to
      RANKL activity. Here, using oligonucleotide microarrays and quantitative
      polymerase chain reaction, we explored potential upstream mechanisms for these
      effects. Ritonavir, but not the HIV PIs indinavir or nelfinavir, up-regulated the
      production of transcripts for OC growth factors and the non-canonical Wnt
      Proteins 5B and 7B as well as activated promoters of nuclear factor-kappaB
      signaling, but suppressed genes involved in canonical Wnt signaling. Similarly,
      ritonavir blocked the cytoplasmic to nuclear translocation of beta-catenin, the
      molecular node of the Wnt signaling pathway, in association with enhanced beta
      catenin ubiquitination. Exposure of OC precursors to LiCl, an inhibitor of the
      canonical Wnt antagonist GSK-3beta, suppressed OC differentiation, as did
      adenovirus-mediated overexpression of beta-catenin. These data identify, for the
      first time, a biologically relevant role for Wnt signaling via beta-catenin in
      isolated OC precursors and the modulation of Wnt signaling by ritonavir. The
      reversal of these ritonavir-mediated changes by interferon-gamma provides a model
      for possible intervention in this metabolic complication of HIV therapy.

PMID- 19095958
TI  - p47phox deficiency induces macrophage dysfunction resulting in progressive
      crystalline macrophage pneumonia.
AB  - Nicotinamide dinucleotide phosphate oxidase-deficient (p47(phox-/-)) mice are a
      model of human chronic granulomatous disease; these mice are prone to develop
      systemic infections and inflammatory diseases. The use of antibiotic (Bactrim)
      prophylaxis in a specific pathogen-free environment, however, impedes infection
      in the majority of p47(phox-/-) mice. We examined infection-free p47(phox-/-)
      mice between 1 and 14 months of age and found that they developed proliferative
      macrophage lesions containing Ym1/Ym2 protein and crystals in lung, bone marrow,
      lymph nodes, and spleen. Here, we show that the lung lesions progressed from
      single macrophages with intracellular Ym1/Ym2 protein crystals to severe diffuse
      crystalline macrophage pneumonia without histological evidence of either
      granulation tissue or pulmonary fibrosis. Ym1/Ym2 is a chitinase-like secretory
      protein that is transiently induced in alternatively activated macrophages during
      T-helper (Th)2-biased pathogenesis and during chemical and traumatic
      inflammation. Bronchoalveolar lavage from p47(phox-/-) mice contained
      significantly higher levels of Th-1 (interferon-gamma), Th-2 (interleukin-4), and
      Th-17 (interleukin-17)-associated cytokines than wild-type mice, as well as
      copious amounts of interleukin-12, indicating that Ym1-secreting p47(phox-/-)
      macrophages are also integrated into classically activated macrophage responses.
      These results suggest that p47(phox-/-) macrophages are extremely pliable, due in
      part to an intrinsic dysfunction of macrophage activation pathways that allows
      for distinct classical or alternative activation phenotypes.

PMID- 19095959
TI  - Adipose tissue sensitivity to radiation exposure.
AB  - Treatment of cancer using radiation can be significantly compromised by the
      development of severe acute and late damage to normal tissue. Treatments that
      either reduce the risk and severity of damage or that facilitate the healing of
      radiation injuries are being developed, including autologous adipose tissue
      grafts to repair tissue defects or involutional disorders that result from tumor
      resection. Adipose tissue is specialized in energy storage and contains different
      cell types, including preadipocytes, which could be used for autologous
      transplantation. It has long been considered a poorly proliferative connective
      tissue; however, the acute effects of ionizing radiation on adipose tissue have
      not been investigated. Therefore, the aim of this study was to characterize the
      alterations induced in adipose tissue by total body irradiation. A severe
      decrease in proliferating cells, as well as a significant increase in apoptotic
      cells, was observed in vivo in inguinal fat pads following irradiation.
      Additionally, irradiation altered the hematopoietic population. Decreases in the
      proliferation and differentiation capacities of non-hematopoietic progenitors
      were also observed following irradiation. Together, these data demonstrate that
      subcutaneous adipose tissue is very sensitive to irradiation, leading to a
      profound alteration of its developmental potential. This damage could also alter
      the reconstructive properties of adipose tissue and, therefore, calls into
      question its use in autologous fat transfer following radiotherapy.

PMID- 19095960
TI  - A physical mechanism for coupling bone resorption and formation in adult human
      bone.
AB  - During skeletal remodeling, pre-osteoclasts and pre-osteoblasts are targeted to
      critical sites of the bone to resorb and reconstruct bone matrix, respectively.
      Coordination of site-specific recruitment of these two cell types is a
      prerequisite to maintain the specific architecture of each bone within strict
      limits throughout adult life. Here, we determined that the bone marrow
      microanatomy adjacent to remodeling areas is a central player in this process. By
      using histomorphometry and multiple immunostainings, we demonstrated in biopsies
      exhibiting coupled bone resorption and formation that osteoclasts and osteoblasts
      on the bone surface were always covered by a canopy of flat cells expressing
      osteoblast markers. In contrast, in biopsies in which this canopy was disrupted,
      bone formation was deficient. Three-dimensional visualizations revealed that this
      canopy covered the entire remodeling site and was associated with capillaries,
      thereby forming a previously unrecognized microanatomical entity. Furthermore,
      pre-osteoclasts were positioned along these capillaries. These findings led to a
      model that implicates vasculature in the site-specific recruitment of osteoclasts
      and osteoblasts and embraces the current knowledge on the molecular mechanism of
      bone remodeling.

PMID- 19095961
TI  - A C-type lectin MGL1/CD301a plays an anti-inflammatory role in murine
      experimental colitis.
AB  - Inflammatory bowel disease is caused by abnormal inflammatory and immune
      responses to harmless substances, such as commensal bacteria, in the large bowel.
      Such responses appear to be suppressed under healthy conditions, although the
      mechanism of such suppression is currently unclear. The present study aimed to
      reveal whether the recognition of bacterial surface carbohydrates by the
      macrophage galactose-type C-type lectin-1, MGL1/CD301a, induces both the
      production and secretion of interleukin (IL)-10. Dextran sulfate sodium salt
      (DSS) was orally administrated to mice that lacked MGL1/CD301a (Mgl1(-/-) mice)
      and their wild-type littermates. Mgl1(-/-) mice showed significantly more severe
      inflammation than wild-type mice after administration of DSS. MGL1-positive cells
      in the colonic lamina propria corresponded to macrophage-like cells with F4/80
      high, CD11b-positive, and CD11c-intermediate expression. These cells in Mgl1(-/-)
      mice produced a lower level of IL-10 mRNA compared with wild-type mice after the
      administration of DSS for 2 days. Recombinant MGL1 was found to bind both
      Streptococcus sp. and Lactobacillus sp. among commensal bacteria isolated from
      mesenteric lymph nodes of DSS-treated mice. Heat-killed Streptococcus sp. induced
      an increase in IL-10 secretion by MGL1-positive colonic lamina propria
      macrophages, but not the macrophage population from Mgl1(-/-) mice. These results
      strongly suggest that MGL1/CD301a plays a protective role against colitis by
      effectively inducing IL-10 production by colonic lamina propria macrophages in
      response to invading commensal bacteria.

PMID- 19095962
TI  - Renal ischemia-induced cholesterol loading: transcription factor recruitment and
      chromatin remodeling along the HMG CoA reductase gene.
AB  - Acute kidney injury evokes renal tubular cholesterol synthesis. However, the
      factors during acute kidney injury that regulate HMG CoA reductase (HMGCR)
      activity, the rate-limiting step in cholesterol synthesis, have not been defined.
      To investigate these factors, mice were subjected to 30 minutes of either
      unilateral renal ischemia or sham surgery. After 3 days, bilateral nephrectomy
      was performed and cortical tissue extracts were prepared. The recruitment of RNA
      polymerase II (Pol II), transcription factors (SREBP-1, SREBP-2, NF-kappaB, c
      Fos, and c-Jun), and heat shock proteins (HSP-70 and heme oxygenase-1) to the
      HMGCR promoter and transcription region (start/end exons) were assessed by Matrix
      ChIP assay. HMGCR mRNA, protein, and cholesterol levels were determined. Finally,
      histone modifications at HMGCR were assessed. Ischemia/reperfusion (I/R) induced
      marked cholesterol loading, which corresponded with elevated Pol II recruitment
      to HMGCR and increased expression levels of both HMGCR protein and mRNA. I/R also
      induced the binding of multiple transcription factors (SREBP-1, SREBP-2, c-Fos, c
      Jun, NF-kappaB) and heat shock proteins to the HMGCR promoter and transcription
      regions. Significant histone modifications (increased H3K4m3, H3K19Ac, and H2A.Z
      variant) at these loci were also observed but were not identified at either the
      5' and 3' HMGCR flanking regions (+/-5000 bps) or at negative control genes (beta
      actin and beta-globin). In conclusion, I/R activates the HMGCR gene via multiple
      stress-activated transcriptional and epigenetic pathways, contributing to renal
      cholesterol loading.

PMID- 19095964
TI  - Failure of pelvic organ support in mice deficient in fibulin-3.
AB  - Fibulin-5 is crucial for normal elastic fiber synthesis in the vaginal wall; more
      than 90% of fibulin-5-knockout mice develop pelvic organ prolapse by 20 weeks of
      age. In contrast, fibulin-1 and -2 deficiencies do not result in similar
      pathologies, and fibulin-4-knockout mice die shortly after birth. EFEMP1 encodes
      fibulin-3, an extracellular matrix protein important in the maintenance of
      abdominal fascia. Herein, we evaluated the role of fibulin-3 in pelvic organ
      support. Pelvic organ support was impaired significantly in female Efemp1
      knockout mice (Fbln3(-[supi]/-)), and overt vaginal, perineal, and rectal
      prolapse occurred in 26.9% of animals. Prolapse severity increased with age but
      not parity. Fibulin-5 was up-regulated in vaginal tissues from Fbln3(-[supi]/-)
      mice regardless of prolapse. Despite increased expression of fibulin-5 in the
      vaginal wall, pelvic organ support failure occurred in Fbln3(-[supi]/-) animals,
      suggesting that factors related to aging led to prolapse. Elastic fiber
      abnormalities in vaginal tissues from young Fbln3(-[supi]/-) mice progressed to
      severe elastic fiber disruption with age, and vaginal matrix metalloprotease
      activity was increased significantly in Fbln3(-[supi]/-) animals with prolapse
      compared with Fbln3(-[supi]/-) mice without prolapse. Overall, these results
      indicate that both fibulin-3 and -5 are important in maintaining pelvic organ
      support in mice. We suggest that increased vaginal protease activity and abnormal
      elastic fibers in the vaginal wall are important components in the pathogenesis
      of pelvic organ prolapse.

PMID- 19095965
TI  - Muscleblind-like proteins: similarities and differences in normal and myotonic
      dystrophy muscle.
AB  - In myotonic dystrophy, muscleblind-like protein 1 (MBNL1) protein binds
      specifically to expanded CUG or CCUG repeats, which accumulate as discrete
      nuclear foci, and this is thought to prevent its function in the regulation of
      alternative splicing of pre-mRNAs. There is strong evidence for the role of the
      MBNL1 gene in disease pathology, but the roles of two related genes, MBNL2 and
      MBNL3, are less clear. Using new monoclonal antibodies specific for each of the
      three gene products, we found that MBNL2 decreased during human fetal development
      and myoblast culture, while MBNL1 was unchanged. In Duchenne muscular dystrophy
      muscle, MBNL2 was elevated in immature, regenerating fibres compared with mature
      fibres, supporting some developmental role for MBNL2. MBNL3 was found only in
      C2C12 mouse myoblasts. Both MBNL1 and MBNL2 were partially sequestered by nuclear
      foci of expanded repeats in adult muscle and cultured cells from myotonic
      dystrophy patients. In adult muscle nucleoplasm, both proteins were reduced in
      myotonic dystrophy type 1 compared with an age-matched control. In normal human
      myoblast cultures, MBNL1 and MBNL2 always co-distributed but their distribution
      could change rapidly from nucleoplasmic to cytoplasmic. Functional differences
      between MBNL1 and MBNL2 have not yet been found and may prove quite subtle. The
      dominance of MBNL1 in mature, striated muscle would explain why ablation of the
      mouse mbnl1 gene alone is sufficient to cause a myotonic dystrophy.

PMID- 19095967
TI  - Differences in the nature of stroke in a multiethnic urban South African
      population: the Johannesburg hospital stroke register.
AB  - BACKGROUND AND PURPOSE: The burden of stroke is increasing in Sub-Saharan Africa
      (SSA) as the population undergoes epidemiological and demographic transition.
      Little is known about the nature (risk factors, stroke type and subtype, and
      causes) of stroke in SSA and whether it differs from stroke in high-income
      populations. We aimed to compare the nature of stroke between black and white
      populations in South Africa. METHODS: We used overlapping sources to ascertain
      consecutive first-ever-in-a-lifetime stroke patients admitted to Johannesburg
      Hospital over 23 months. We assessed each patient's demographic details, risk
      factors, CT confirmed pathological stroke type, ischemic stroke subtype and
      stroke severity, and compared the nature of stroke between black and white stroke
      patients. RESULTS: 524 patients with presumed stroke were referred. Of these, 432
      were first-ever strokes; 308 patients were black and 76 white. Black patients
      were significantly younger (mean age 51) than white patients (61). Stroke
      severity was similar (median NIH stroke score 10; 95% CI 8 to 11). More black
      than white patients had cerebral hemorrhage (27% versus 15%), lacunar stroke (28%
      versus 22%) and total anterior circulation infarcts (28% versus 22%). Large
      vessel atherosclerosis (none detected) and ischemic heart disease were very
      uncommon (1%) as a cause of stroke in black patients. Hypertension (70% versus
      68%) and diabetes (14 versus 15%) were as common in black and white stroke
      patients, but mean cholesterol levels were lower (4.6 mmol/L; 95% CI 4.3 to 4.9
      versus 5.3 mmol/L; 4.8 to 5.7) and cigarette smoking less frequent in black
      patients (23 versus 54%). CONCLUSIONS: Although this was a hospital-based study,
      the difference in the nature of stroke between black and white stroke patients
      likely reflects the profile of stroke risk factors. There is an opportunity to
      prevent an otherwise inevitable increase in atherosclerotic stroke (and IHD) by
      targeting dietary and smoking habits in the black South African population.

PMID- 19095966
TI  - Potential role of PUMA in delayed death of hippocampal CA1 neurons after
      transient global cerebral ischemia.
AB  - BACKGROUND AND PURPOSE: p53-upregulated modulator of apoptosis (PUMA), a BH3-only
      member of the Bcl-2 protein family, is required for p53-dependent and 
      independent forms of apoptosis. PUMA localizes to mitochondria and interacts with
      antiapoptotic Bcl-2 and Bcl-X(L) or proapoptotic Bax in response to death
      stimuli. Although studies have shown that PUMA is associated with pathomechanisms
      of cerebral ischemia, clearly defined roles for PUMA in ischemic neuronal death
      remain unclear. The purpose of this study was to determine potential roles for
      PUMA in cerebral ischemia. METHODS: Five minutes of transient global cerebral
      ischemia (tGCI) were induced by bilateral common carotid artery occlusion
      combined with hypotension. RESULTS: PUMA was upregulated in vulnerable
      hippocampal CA1 neurons after tGCI as shown by immunohistochemistry. In Western
      blot and coimmunoprecipitation analyses, PUMA localized to mitochondria and was
      bound to Bcl-X(L) and Bax in the hippocampal CA1 subregion after tGCI. PUMA
      upregulation was inhibited by pifithrin-alpha, a specific inhibitor of p53,
      suggesting that PUMA is partly controlled by the p53 transcriptional pathway
      after tGCI. Furthermore, reduction in oxidative stress by overexpression of
      copper/zinc superoxide dismutase, which is known to be protective of vulnerable
      ischemic hippocampal neurons, inhibited PUMA upregulation and subsequent
      hippocampal CA1 neuronal death after tGCI. CONCLUSIONS: These results imply a
      potential role for PUMA in delayed CA1 neuronal death after tGCI and that it
      could be a molecular target for therapy.

PMID- 19095968
TI  - The cost of stroke prevention.

PMID- 19095969
TI  - Edaravone, a free radical scavenger, inhibits MMP-9-related brain hemorrhage in
      rats treated with tissue plasminogen activator.
AB  - BACKGROUND AND PURPOSE: Intracerebral hemorrhage, induced by recombinant tissue
      plasminogen activator (rtPA) in ischemic stroke, is attributable to the increased
      activity of matrix metalloproteinase-9 (MMP-9). Patients with acute infarct
      benefit from the neuroprotective drug edaravone, a free radical scavenger. We
      examined the mechanisms by which edaravone may help to suppress rtPA-induced
      brain hemorrhage. METHODS: Male Wistar rats weighing 250 to 280 g were subjected
      to 3-hour transient middle cerebral artery occlusion (MCAO) and divided randomly
      into 3 groups. Immediately after reperfusion, 1 group was intravenously injected
      with 10 mg/kg rtPA, another with rtPA plus 3 mg/kg edaravone, and the 3rd group
      received no treatment. We assessed the hemorrhage volume and the activity of MMP
      9 in the brain 24 hours postischemia. We also studied the activity of MMP-9, its
      mRNA expression, and nuclear factor-kappa B (NF-kappaB) activity in rtPA
      stimulated human microvascular endothelial cells (HBECs). RESULTS: The degree of
      hemorrhage and the level of endothelial cell-derived MMP-9 were elevated in rats
      treated with rtPA alone and attenuated in rats treated with rtPA plus edaravone.
      In rtPA-stimulated HBECs, edaravone suppressed the activity and mRNA expression
      of MMP-9 in a dose-dependent manner. Edaravone also inhibited NF-kappaB
      activation. CONCLUSIONS: We demonstrate that edaravone inhibits rtPA-induced
      cerebral hemorrhage in the ischemic brain of rats via the inhibition of MMP-9
      expression in vivo, which is substantiated by inhibition of MMP-9 expression and
      NF-kappaB activation in HBECs. Edaravone may render thrombolytic therapy safer
      for the administration of rtPA in patients with ischemic stroke.

PMID- 19095970
TI  - The prognostic value of capillary glucose levels in acute stroke: the GLycemia in
      Acute Stroke (GLIAS) study.
AB  - BACKGROUND AND PURPOSE: Evidence is accumulating regarding the prognostic
      influence of hyperglycemia in patients with acute ischemic stroke. However, the
      level associated with poor outcome is unknown. Our objectives were to establish
      the capillary glucose threshold with the highest predictive accuracy of poor
      outcome and to evaluate its hypothetical value in influencing functional outcome
      by adjusting for other well-known prognostic factors in acute stroke. METHODS:
      The authors conducted a multicenter, prospective, and observational cohort study
      of 476 patients with ischemic stroke within less than 24 hours from stroke onset.
      Capillary finger-prick glucose and stroke severity were determined on admission
      and 3 times a day during the first 48 hours. Poor outcome (modified Rankin Scale
      >2) was evaluated at 3 months. RESULTS: The receiver operating characteristic
      curves showed the predictive value of maximum capillary glucose at any time
      within the first 48 hours with an area under the curve of 0.656 (95% CI, 0.592 to
      0.720; P<0.01) and pointed to 155 mg/dL as the optimal cutoff level for poor
      outcome at 3 months (53% sensitivity; 73% specificity). This point was associated
      with a 2.7-fold increase (95% CI, 1.42 to 5.24) in the odds of poor outcome after
      adjustment for age, diabetes, capillary glucose on admission, infarct volume, and
      baseline stroke severity and with a 3-fold increase in the risk of death at 3
      months (hazard ratio, 3.80; 95% CI, 1.79 to 8.10). CONCLUSIONS: Hyperglycemia
      >or=155 mg/dL at any time within the first 48 hours from stroke onset, and not
      only the isolated value of admission glycemia, is associated with poor outcome
      independently of stroke severity, infarct volume, diabetes, or age.

PMID- 19095971
TI  - A spectrum of knock-type Doppler signals in the intracranial vessels.
AB  - BACKGROUND AND PURPOSE: Knock-type Doppler signals (KTDS) are detectable by
      transcranial Doppler, and it has been hypothesized that they are related to an
      occlusion of a small perforating artery and microvascular ischemia. However, the
      nature of KTDS has not been prospectively defined. We aimed at describing the
      spectral and power motion Doppler characteristics of KTDS and ultrasound exposure
      conditions that lead to their appearance. METHODS: Consecutive patients referred
      with symptoms of stroke or transient ischemic attacks to our cerebrovascular
      ultrasound laboratory were screened for the presence of KTDS. The presence of
      microvascular ischemia was assessed using brain MRI. RESULTS: Among 327 patients
      with cerebrovascular symptoms, 46 (14%) had KTDS. KTDS were found more frequently
      in posterior circulation vessels (55% vertebral artery, 21.5% basilar artery, and
      6% posterior cerebral artery). There was no association between ultrasound
      identification of KTDS and the presence of brain ischemia in the distribution of
      any vessel (OR, 0.37; 95% CI, 0.09-1.53; P=0.171) on univariate logistic
      regression analyses. KTDS was not related to the presence of microvascular
      ischemia on brain MRI (OR, 1.12; 95% CI, 0.55-2.29; P=0.761). We described the
      range of spectral and power motion Doppler appearances of KTDS and experimentally
      demonstrated the most likely underlying mechanism being a large vessel wall
      movement artifact. CONCLUSIONS: Although KTDS can be distinguished from other
      spectral flow signals, they can be found in normal vessels, they do not seem to
      be associated with the vessel affected by ischemia, and they should not be
      overinterpreted.

PMID- 19095972
TI  - Doppler ultrasound detection of side-vessel occlusion: an in vitro study.
AB  - BACKGROUND AND PURPOSE: Small-vessel knock is a recently reported Doppler
      ultrasound finding that has been identified in patients with cerebral ischemia.
      It has been hypothesized that knock-type signals are linked to the presence of
      either small-vessel occlusion or wall motion. The aim of this study was to
      investigate the origins of "knock-type" signals by reproducing occlusion of a
      peripheral artery model in vitro. METHODS: Synthetic bifurcations were fabricated
      from glass and latex and placed in a flow-rig mimicking physiological blood-flow
      conditions. The glass model permitted study of fluid flow in the absence of wall
      motion, whereas the latex model also produced wall motion effects. Vessels were
      artificially obstructed to examine Doppler signal characteristics associated with
      blood flow and wall motion. RESULTS: Complete obstruction of the peripheral
      branch of the glass model revealed discrete (<100 ms) knock-type signals caused
      by local fluid flow in the occluded branch. Imaging of the obstructed vessel
      using color Doppler revealed forward and reflected flow. The walls produced
      periodic bidirectional knock-type signals, which occurred during systole and were
      not related to the presence of an obstruction. CONCLUSIONS: In our laboratory
      model, transcranial Doppler ultrasound was found to be capable of detecting knock
      signals produced by circulating fluid within an occluded branch. However, because
      similar signals are also generated by nonpathological wall motion, these results
      cannot be directly translated to a clinical setting. Clinicians should be careful
      to avoid casual overinterpretation of transcranial Doppler ultrasound data.

PMID- 19095973
TI  - Psychosocial functioning of spouses of patients with stroke from initial
      inpatient rehabilitation to 3 years poststroke: course and relations with coping
      strategies.
AB  - BACKGROUND AND PURPOSE: Few studies have focused on long-term changes in the
      caregiving experience after stroke. This study assessed changes in the
      psychosocial functioning of spouses (burden, depressive symptoms, harmony in the
      relationship between patient and spouse, and social relations) during the first 3
      years after stroke and identified predictors of the course of spouses'
      psychosocial functioning based on the characteristics of patients and spouses
      with special emphasis on coping style. METHODS: We examined 211 couples shortly
      after the patient's admission to a rehabilitation center, 197 2 months after
      discharge, 187 1 year poststroke, and 121 3 years poststroke. Burden was assessed
      using the Caregiver Strain Index, depressive symptoms with the Goldberg
      Depression Scale, harmony in the relationship with the Interactional Problem
      Solving Inventory, and social relations with the Social Support List. Multilevel
      regression analyses were performed. RESULTS: A significant effect of time
      (P<0.01) was found for all 4 aspects of spouses' psychosocial functioning.
      Although burden decreased, harmony in the relationship and social relations also
      decreased. The depression score showed a nonlinear pattern with an initial
      decrease but a long-term increase. All outcomes were significantly related to
      caregiver coping strategies. A total of 15% to 27% of the variance in
      psychosocial functioning could be explained. CONCLUSIONS: Follow-up of spouses of
      patients with stroke requires not only assessment of burden, but also other
      aspects of psychosocial functioning like harmony in the relationship, depression,
      and social relations, because our results show negative long-term consequences of
      stroke for these aspects of caregiver quality of life.

PMID- 19095975
TI  - Serial diffusion imaging in a case of mitochondrial encephalomyopathy, lactic
      acidosis, and stroke-like episodes.
AB  - BACKGROUND AND PURPOSE: Most diffusion MRI studies of mitochondrial
      encephalomyopathy, lactic acidosis, and stroke-like episode stroke-like lesions
      report high- or normal-apparent diffusion coefficient, and this has been used to
      differentiate stroke-like lesion from ischemic stroke. There are, however, 3
      recent reports of restricted diffusion in the acute phase of the stroke-like
      lesions. The purpose of our study was to investigate this apparent paradox.
      METHODS: We performed 9 serial MRI covering 2 stroke-like episodes in a 36-year
      old man with mitochondrial encephalomyopathy, lactic acidosis, and stroke-like
      episode caused by the common mitochondrial DNA mutation 3243A>G. RESULTS: We
      found clear evidence of initial restricted diffusion in the stroke-like lesions,
      which gradually evolved to high-apparent diffusion coefficient as lesions aged.
      Evolution was, however, asynchronous with both high- and low-apparent diffusion
      coefficients temporally coexisting. CONCLUSIONS: Our findings suggest that
      cytotoxic edema does occur early in the course of a stroke-like lesions and that
      its presence or, conversely, the absence of vasogenic edema, should not weaken
      the possibility of mitochondrial encephalomyopathy, lactic acidosis, and stroke
      like episode in favor of ischemic stroke.

PMID- 19095974
TI  - Lipoprotein-associated phospholipase A2 and high-sensitivity C-reactive protein
      improve the stratification of ischemic stroke risk in the Atherosclerosis Risk in
      Communities (ARIC) study.
AB  - BACKGROUND AND PURPOSE: Inflammation plays a critical role in the development of
      vascular disease, and increased levels of the inflammatory biomarkers,
      lipoprotein-associated phospholipase A(2) (Lp-PLA(2)), and high-sensitivity C
      reactive protein (hs-CRP) have been shown to be associated with an increased risk
      for ischemic stroke. METHODS: In a prospective case-cohort (n=949) study in 12
      762 apparently healthy, middle-aged men and women in the Atherosclerosis Risk in
      Communities (ARIC) study, we first examined whether Lp-PLA(2) and hs-CRP levels
      improved the area under the receiver operator characteristic curve (AUC) for 5
      year ischemic stroke risk. We then examined how Lp-PLA(2) and hs-CRP levels
      altered classification of individuals into low-, intermediate-, or high-risk
      categories compared with traditional risk factors. RESULTS: In a model using
      traditional risk factors alone, the AUC adjusted for optimism was 0.732, whereas
      adding hs-CRP improved the AUC to 0.743, and adding Lp-PLA(2) significantly
      improved the AUC to 0.752. Addition of hs-CRP and Lp-PLA(2) together in the model
      improved the AUC to 0.761, and the addition of the interaction between Lp-PLA(2)
      and hs-CRP further significantly improved the AUC to 0.774. With the use of
      traditional risk factors to assess 5-year risk for ischemic stroke, 86% of
      participants were categorized as low risk (<2%); 11%, intermediate risk (2% to
      5%); and 3%, high risk (>5%). The addition of hs-CRP, Lp-PLA(2), and their
      interaction to the model reclassified 4%, 39%, and 34% of the low-, intermediate-
      and high-risk categories, respectively. CONCLUSIONS: Lp-PLA(2) and hs-CRP may be
      useful in individuals classified as intermediate risk for ischemic stroke by
      traditional risk factors.

PMID- 19095976
TI  - Venous hemodynamics may enhance collateral perfusion and the fibrinolytic milieu
      in paradoxical embolism.

PMID- 19095977
TI  - No association of the plasma glutathione peroxidase (GPx-3) gene with cerebral
      venous thrombosis in the German population.

PMID- 19095978
TI  - Should right-to-left shunts be detected before thrombolysis in acute ischemic
      stroke patients?

PMID- 19095979
TI  - Recurrent events in transient ischemic attack and minor stroke.

PMID- 19095980
TI  - Cathepsin enzymes and cystatin C: do they play a role in positive arterial
      remodeling?

PMID- 19095981
TI  - 25-Hydroxyvitamin d and risk of stroke: possible mediation by statin therapy?

PMID- 19095982
TI  - Low vitamin D levels and bone mineral density in stroke.

PMID- 19095983
TI  - Novel LMNA mutation in atypical Werner syndrome presenting with ischemic disease.
AB  - BACKGROUND AND PURPOSE: Laminopathies arise through mutations in genes encoding
      Lamin A/C (LMNA) or associated proteins. They cause 4 different groups of
      disorders with diverse severity and often overlapping features: diseases of
      striated muscle (leading to muscular or cardiac involvement), peripheral
      neuropathy, lipodystrophy syndromes, and accelerated aging disorders. SUMMARY OF
      CASE: We report on a familial case of atypical Werner syndrome (a progeroid
      syndrome with Werner syndrome phenotype but without typical RECQL2 mutation)
      presenting with acute ischemic cerebral disease or peripheral artery disease
      associated with diffuse atherosclerosis, attributable to transmission of a novel
      LMNA mutation. CONCLUSIONS: In young patients with ischemic events and a positive
      family history, other progeroid features have to be searched and LMNA testing has
      to be considered, allowing for genetic counseling and presymptomatic testing of
      at-risk relatives.

PMID- 19095984
TI  - Long-term health-related quality of life after aneurysmal subarachnoid
      hemorrhage: relationship with psychological symptoms and personality
      characteristics.
AB  - BACKGROUND AND PURPOSE: Many patients who survive an aneurysmal subarachnoid
      hemorrhage experience decreased health-related quality of life (HRQoL). Physical
      factors have been identified as determinants of HRQoL. We describe long-term
      HRQoL and assessed whether psychological symptoms and personality characteristics
      determine HRQoL after subarachnoid hemorrhage. METHODS: In a cross-sectional
      study in 141 patients living independently in the community 2 to 4 years after
      subarachnoid hemorrhage, we assessed whether HRQoL, evaluated by the Stroke
      Specific Quality of Life scale, was related to psychological symptoms (mood
      disorders, fatigue, and cognitive complaints), personality characteristics
      (neuroticism and passive coping style), demographic characteristics, and
      subarachnoid hemorrhage disease characteristics. RESULTS: Best Stroke Specific
      Quality of Life scale scores were found in the physical domain and worst in the
      emotional and social domains. Thirty-two percent reported anxiety, 23%
      depression, and 67% fatigue. Mood (beta between -0.42 and -0.18), fatigue (beta
      between -0.40 and -0.24), and cognitive complaints (beta between -0.46 and -0.16)
      were strongly associated with Stroke Specific Quality of Life scale scores in
      multivariate regression analyses. CONCLUSIONS: Depression, anxiety, and fatigue
      were present in a substantial proportion of patients and were strongly related to
      decreased HRQoL. These symptoms identified are helpful to tailor rehabilitation
      to the needs of patients in the chronic phase after subarachnoid hemorrhage.

PMID- 19095985
TI  - Enhanced contractile response of the basilar artery to platelet-derived growth
      factor in subarachnoid hemorrhage.
AB  - BACKGROUND AND PURPOSE: The level of platelet-derived growth factor (PDGF) in
      cerebrospinal fluid is elevated in subarachnoid hemorrhage (SAH). Therefore, the
      contractile effect of PDGF on the basilar artery was examined in SAH. METHODS: A
      rabbit double-hemorrhage SAH model was used. In the medial layers of the control
      basilar artery, PDGF had no effect on contraction up to 1 nmol/L, whereas 3
      nmol/L PDGF induced slight contraction. In SAH, PDGF induced an enhanced
      contraction with an increase in [Ca(2+)](i) at 1 nmol/L and higher
      concentrations. The levels of [Ca(2+)](i) and tension induced by 1 nmol/L PDGF in
      SAH were 17% and 20%, respectively, of those obtained with 118 mmol/L K(+)
      depolarization. The PDGF-induced elevation of [Ca(2+)](i) and contraction seen in
      SAH were abolished in the absence of extracellular Ca(2+). In alpha-toxin
      permeabilized strips of SAH animals, PDGF induced no further development of
      tension during contraction induced by 300 nmol/L Ca(2+), suggesting no direct
      effect on myofilament Ca(2+) sensitivity. Genistein at 10 micromol/L completely
      inhibited the tension induced by 1 nmol/L PDGF. The level of myosin light-chain
      phosphorylation was significantly increased by 1 nmol/L PDGF. CONCLUSIONS: These
      results show that the contractile response to PDGF of the basilar artery was
      enhanced in SAH. The PDGF-induced contraction depended mostly on tyrosine
      phosphorylation and Ca(2+)-dependent myosin light-chain phosphorylation. The
      enhancement of the responsiveness to PDGF may therefore contribute to the
      development of cerebral vasospasm after SAH.

PMID- 19095986
TI  - Flow-mediated vascular remodeling in hypertension: relation to hemodyamics.
AB  - BACKGROUND AND PURPOSE: Changes in shear and medial wall stress induced by blood
      flow contribute to vascular remodeling, but details of these relations remain
      undefined. We hypothesized that remodeling has a strong genetic component and
      that phenotypic responses to hemodynamic stress will differ among rat strains.
      Here, we characterized phenotypic traits related to carotid remodeling in the 2
      rat strains that we previously showed the greatest difference in shear stress
      regulation: Genetically Hypertensive (GH) and Brown Norway (BN) rat strains.
      METHODS: Left internal and external carotid arteries were ligated and blood flow
      was reduced in the left common (LCA) by 90% and increased in the right common
      carotid artery (RCA) by 60%. Rats were studied for up to 28 days after flow
      modification and carotid outer diameters were measured in vivo, and wall and
      luminal components by histomorphometry, to obtain indices of remodeling. Blood
      flow and pressure measurements were made at corresponding time points. RESULTS:
      By day 28, remodeling in the GH was greater in response to high flow than in BN,
      and shear stress was normalized. In contrast, remodeling in the BN was greater in
      the low flow LCA than in GH. Media stress was greater in GH than BN for any value
      of carotid shear stress and remained relatively unchanged in low flow, but
      markedly increased in high flow remodeling. Importantly, pressure was not a major
      determinant of flow remodeling in these conditions. CONCLUSIONS: There are key
      differences in the ability of carotids in GH and BN rats to adhere to hemodynamic
      laws during vascular remodeling. GH rats exhibit intact regulatory mechanisms for
      increased, but not reduced, shear stress. Moreover, the ability to maintain
      physiological shear and media stresses during vascular remodeling in response to
      modified flow appears to be intrinsically "genetically" determined.

PMID- 19095987
TI  - LDL cholesterol and the development of stroke subtypes and coronary heart disease
      in a general Japanese population: the Hisayama study.
AB  - BACKGROUND AND PURPOSE: Although the relation between serum LDL cholesterol level
      and coronary heart disease (CHD) is well established, its relation with stroke
      subtypes is less clear. METHODS: A total of 2351 inhabitants age >or=40 years in
      a Japanese community were followed up for 19 years. RESULTS: During follow-up,
      271 subjects developed stroke and 144 developed CHD. Whereas the age- and sex
      adjusted incidences of CHD significantly increased with increasing LDL
      cholesterol levels (P for trend <0.001), the associations between LDL cholesterol
      level and the incidences of ischemic or hemorrhagic stroke were not significant.
      The age- and sex-adjusted incidences of atherothrombotic infarctions (ATIs) and
      lacunar infarctions (LIs) significantly increased with increasing LDL cholesterol
      level (P for trend=0.03 for ATIs and=0.02 for LIs), but no such association was
      observed for cardioembolic infarction. After multivariate adjustment, the
      positive associations of LDL cholesterol level with the risks of ATI and CHD
      remained significant (P for trend=0.02 for ATIs and=0.03 for CHD), whereas the
      association with LIs was not significant. The risk of ATI significantly increased
      in the fourth quartile of LDL cholesterol compared with the first quartile
      (multivariate-adjusted hazard ratio=2.84; 95% CI, 1.17 to 6.93). The multivariate
      adjusted risks for developing nonembolic infarction (ATIs and LIs) and CHD were
      significantly elevated in the groups with elevated LDL cholesterol values with
      and without the metabolic syndrome. CONCLUSIONS: Our findings suggest that an
      elevated LDL cholesterol level is a significant risk factor for developing ATI as
      well as CHD, and these associations are independent of the metabolic syndrome.

PMID- 19095988
TI  - Increased levels of circulating endothelial progenitor cells in patients with
      Moyamoya disease.
AB  - BACKGROUND AND PURPOSE: Chronic cerebral ischemia leads to higher risk for
      strokes attributable to insufficient collateralization, resulting from inadequate
      capacity for arteriogenesis and angiogenesis. Patients with Moyamoya disease
      (MMD) have similar transient ischemic attack frequencies compared to patients
      with chronic cerebral ischemia with other etiologies, but a strong capacity for
      arteriogenesis and angiogenesis. The mechanisms involved in the upregulation of
      the arteriogenesis and angiogenesis in MMD still remain unknown. In the present
      study we investigated if circulating endothelial progenitor cells are
      increasingly mobilized during MMD. METHODS: Twenty MMD patients, 8 patients with
      atherosclerotic cerebrovascular disease, and 15 healthy individuals were included
      in this study. Peripheral blood mononuclear cells were isolated by Ficoll density
      gradient centrifugation and circulating endothelial progenitor cells were
      characterized by triple staining using antibodies against CD133, CD34, and
      vascular endothelial growth factor receptor-2. Serum concentrations of vascular
      endothelial growth factor and granulocyte-macrophage colony-stimulating factor
      were determined by enzyme-linked immunosorbent assay. RESULTS: In MMD patients
      the number of circulating endothelial progenitor cells was significantly higher
      than in atherosclerotic cerebrovascular disease patients (P<0.002) and healthy
      controls (P<0.0001). Serum vascular endothelial growth factor concentrations in
      MMD patients and in atherosclerotic cerebrovascular disease patients were
      significantly higher compared to those in healthy controls (P<0.0001). Similar
      findings were observed for granulocyte-macrophage colony-stimulating factor. An
      inverse correlation between circulating endothelial progenitor cell numbers and
      serum levels of vascular endothelial growth factor (r=-0.53; P<0,02) was found in
      the MMD group. CONCLUSIONS: Our results show increased circulating endothelial
      progenitor cell numbers in MMD, which may play a role in the increased
      arteriogenesis and angiogenesis in MMD. Moreover, our results suggest that
      increased circulating endothelial progenitor cell mobilization in MMD may not be
      entirely mediated by vascular endothelial growth factor or granulocyte-macrophage
      colony-stimulating factor.

PMID- 19095989
TI  - Retinopathy in ischemic stroke subtypes.
AB  - BACKGROUND AND PURPOSE: Lacunar stroke is associated with an intrinsic cerebral
      small vessel disorder of unknown etiology, although possible causes include
      increased blood-brain barrier permeability. Retinal arterioles are similar to
      cerebral small vessels and retinopathy occurs secondary to increased blood
      retinal barrier permeability. We hypothesized that there would be higher rates of
      retinopathy in patients with acute lacunar versus cortical stroke. METHODS: We
      prospectively recruited patients presenting with acute lacunar and cortical
      ischemic stroke. An experienced stroke physician diagnosed and subtyped the
      stroke based on clinical features and cerebral MRI. We performed 6 dilated
      digital retinal photographs of each eye in all patients. A carefully trained
      physician graded retinopathy (one or more of hard or soft exudates,
      microaneurysms, or hemorrhages) blind to stroke type as definitely present/absent
      or uncertain. RESULTS: We recruited 220 patients; 6 were excluded with
      ungradeable photographs leaving 214 patients for analysis (105 lacunar and 109
      cortical strokes). Mean age was 68 years (SD, 11 years) and median National
      Institutes of Health Stroke Scale 2. Similar proportions of each group had
      diabetes (17% lacunar versus 10% cortical) and hypertension (56% lacunar and 66%
      cortical). Eighteen percent of lacunar and 19% of cortical patients had any
      retinopathy. After adjusting for baseline differences in age, hypertension, and
      diabetes, retinopathy was not associated with ischemic stroke subtype.
      CONCLUSIONS: We have not demonstrated a strong association between retinopathy
      and ischemic stroke subtype. However, larger samples or assessment of other
      retinal vascular abnormalities may yield positive associations.

PMID- 19095990
TI  - Independent associations between electrocardiographic abnormalities and outcomes
      in patients with aneurysmal subarachnoid hemorrhage: findings from the
      intraoperative hypothermia aneurysm surgery trial.
AB  - BACKGROUND AND PURPOSE: Electrocardiographic abnormalities are common after
      subarachnoid hemorrhage, but their significance remains uncertain. The aim of
      this study was to determine whether any specific electrocardiographic
      abnormalities are independently associated with adverse neurological outcomes.
      METHODS: This was a substudy of the Intraoperative Hypothermia Aneurysm Surgery
      Trial, which was designed to determine whether intraoperative hypothermia would
      improve neurological outcome in patients with subarachnoid hemorrhage undergoing
      aneurysm surgery. The outcome was the 3-month Glasgow Outcome Score treated as
      both a categorical measure (Glasgow Outcome Score 1 [good outcome] to 5 [death])
      and dichotomously (mortality/Glasgow Outcome Score 5 versus Glasgow Outcome Score
      1 to 4). The predictor variables were preoperative electrocardiographic
      characteristics, including heart rate, corrected QT interval, and ST- and T-wave
      abnormalities. Univariate logistic regression was performed to screen for
      significant electrocardiographic variables, which were then tested for
      associations with the outcome by multivariate logistic regression adjusting for
      clinical covariates. RESULTS: The study included 588 patients, of whom 31 (5%)
      died. There was a significant, nonlinear association between heart rate and
      mortality such that lowest quartile (<or=60 beats/min; OR, 6.5; P=0.027) and
      highest quartile (>80 beats/min; OR, 8.8; P=0.006) were associated with higher
      risk. There was also a significant association between nonspecific ST- and T-wave
      abnormalities and mortality (OR, 3.1; P=0.031). CONCLUSIONS: Bradycardia,
      relative tachycardia, and nonspecific ST- and T-wave abnormalities are strongly
      and independently associated with 3-month mortality after subarachnoid
      hemorrhage. Further research should be performed to determine whether there is a
      causal relationship between cardiac dysfunction and neurological outcome after
      subarachnoid hemorrhage.

PMID- 19095991
TI  - Failure of antithrombotic therapy and risk of stroke in patients with symptomatic
      intracranial stenosis.
AB  - BACKGROUND AND PURPOSE: We sought to determine if patients with intracranial
      stenosis who have a transient ischemic attack or stroke on antithrombotic therapy
      are at particularly high risk for recurrent stroke. METHODS: We compared baseline
      features and the rates of stroke or vascular death and stroke in the territory of
      the symptomatic artery between patients ON (n=299) versus OFF (n=269)
      antithrombotics at the time of their qualifying event for the Warfarin-Aspirin
      Symptomatic Intracranial Disease (WASID) trial. RESULTS: In univariate analyses,
      there was no difference in the rates of stroke or vascular death (21% versus 23%;
      hazard ratio [ON/OFF], 0.91; 95% CI, 0.64 to 1.29; P=0.59) or stroke in territory
      (13% versus 14%; hazard ratio [ON/OFF], 0.90; 95% CI, 0.57 to 1.39; P=0.61)
      between patients ON versus OFF antithrombotics at the time of their qualifying
      event. A multivariable analysis adjusted for the difference in risk factors
      between patients ON and OFF antithrombotic therapy also showed no significant
      differences in the combined end point of stroke or vascular death (hazard ratio
      [ON/OFF], 0.86; 95% CI, 0.55 to 1.34; P=0.51) or stroke in territory (hazard
      ratio [ON/OFF], 1.01; 95% CI, 0.58 to 1.77; P=0.97) between patients ON versus
      OFF antithrombotic therapy at the time of the qualifying event. CONCLUSIONS:
      Patients with intracranial stenosis who fail antithrombotic therapy are not at
      higher risk of stroke than those who do not fail antithrombotic therapy. Given
      our finding that patients ON and OFF antithrombotic therapy are both at high risk
      for stroke in the territory, intracranial stenting trials should not be limited
      to just those who fail antithrombotic therapy.

PMID- 19095992
TI  - Atherosclerotic burden findings in young cryptogenic stroke patients with and
      without a patent foramen ovale.
AB  - BACKGROUND AND PURPOSE: To further determine the mechanisms of cryptogenic stroke
      or transient ischemic attack in young patients, we evaluated indices of
      atherosclerosis in patients <or=55 years old diagnosed with cryptogenic
      cerebrovascular event comparing those with patent foramen ovale (PFO) with those
      without PFO. METHODS: This was a prospective study including 100 consecutive
      patients <or=55 years old (mean age, 45+/-8 years; 56 males) diagnosed with
      cryptogenic stroke/transient ischemic attack. PFO was identified in 59 of these
      patients with the use of transesophageal echocardiography with contrast study.
      The following surrogate markers of atherosclerosis were evaluated in all
      patients: carotid intima media thickness as measured by carotid ultrasonography
      and endothelial function as determined by brachial flow-mediated vasodilation.
      The same measurements were obtained in a control group of 50 age- and sex-matched
      control subjects. RESULTS: Patients without PFO were more likely to be current
      smokers and obese and more frequently had a history of hypertension and
      dyslipidemia. Carotid intima media thickness measurements were higher (P<0.0001)
      in patients without PFO (1.03+/-0.31 mm) compared with those with PFO (0.75+/
      0.20 mm) and control subjects (0.79+/-0.17 mm). The absence of PFO was also
      associated with lower brachial flow-mediated vasodilation (without PFO: 5.04+/
      3.39%; with PFO: 7.16+/-4.09%; control subjects: 7.33+/-4.07%; P=0.02). There
      were no differences in carotid intima media thickness and flow-mediated
      vasodilation between patients with stroke/transient ischemic attack with PFO and
      control subjects. The presence of PFO was independently associated with reduced
      carotid intima media thickness (P<0.0001) and increased flow-mediated
      vasodilation (P=0.019). CONCLUSIONS: In patients <or=55 years old diagnosed with
      cryptogenic stroke/transient ischemic attack, the presence of PFO was associated
      with a lower atherosclerotic burden as measured by carotid intima media thickness
      and endothelial function with no differences compared with a control group
      without cerebrovascular event. These results suggest that an atherosclerotic
      mediated mechanism may be involved in cryptogenic stroke/transient ischemic
      attack in patients without PFO, whereas a nonatherosclerotic mechanism may
      mediate the cerebrovascular event in the presence of PFO.

PMID- 19095993
TI  - Stem Cell Therapies as an Emerging Paradigm in Stroke (STEPS): bridging basic and
      clinical science for cellular and neurogenic factor therapy in treating stroke.
AB  - Investigators developing cellular therapy for stroke face many challenges.
      Preclinical models used for cellular therapy studies should be relevant to human
      stroke and predictive of benefit despite differences in stroke size,
      cerebrovascular anatomy, immune status, and neurological responses. Translating
      preclinical testing to human trials is compounded by consideration of delivery
      method and translation of dosing with cell survival. Many issues must be
      approached in designing clinical trials of cellular therapy for stroke, including
      appropriate outcome measures, controlling for confounding factors such as
      rehabilitation therapy, and possible surrogate outcomes using imaging such as MRI
      and newer imaging techniques. It is also important to establish standardized
      clinical protocols and clinical database registries in advance of early proof-of
      concept studies. Investigators must adopt a standardized nomenclature and
      characterization schema for cell products to accurately define potency and
      determine clinical outcome from early proof-of-concept studies. The Stem Cell
      Therapies as an Emerging Paradigm in Stroke (STEPS) meeting was organized to
      bring together clinical and basic researchers with industry and regulatory
      representatives to assess the critical issues in the field and to create a
      framework to guide future investigations.

PMID- 19095994
TI  - Safety and efficacy of endovascular thrombectomy in patients with abnormal
      hemostasis: pooled analysis of the MERCI and multi MERCI trials.
AB  - BACKGROUND AND PURPOSE: Patients with abnormal hemostasis are not considered
      candidates for thrombolysis. We analyzed the MERCI/Multi MERCI cohort as an
      attempt to establish the risks and benefits of thrombectomy in this patient
      population. METHODS: Two patient groups were identified: Group 1 (n=35): patients
      with INR >1.7 or PTT >45 seconds or platelet count <100,000/microL; Group 2
      (n=270): patients with INR <or=1.7, PTT <or=45 seconds, and platelet count
      >or=100,000/microL. Clinical, radiographic, and revascularization outcomes were
      subsequently compared. RESULTS: In Group 1, 20 patients had INR >1.7 (mean: 2.4;
      range: 1.8 to 4.9), 11 had PTT >45 seconds (mean: 95; range: 46 to 190), and 6
      had platelets <100,000/microL (mean: 63 400; range: 16,000 to 94,000). Two
      patients had both INR >1.7 and PTT >45 seconds. The two groups did not
      significantly differ in terms of age, gender, baseline NIHSS scores,
      intraarterial thrombolytic use/dosage, or occlusion site. Time-to-treatment was
      slightly earlier in Group 1. There was no significant difference in the rates of
      revascularization (TIMI 2 to 3: 60% versus 65%), mortality (40% versus 38%), or
      major symptomatic intracranial hemorrhage (SICH; 8.6% versus 8.5%). Group 2 had
      higher rates of good clinical outcomes (9% versus 35%; P=0.002). This was likely
      related to a lower prestroke health status in Group 1 patients. In Group 1,
      successful revascularization was associated with improved outcomes (P=0.015) and
      lower mortality (24% versus 64%; P=0.033). CONCLUSIONS: Patients with abnormal
      hemostasis who undergo thrombectomy do not appear to be at a higher risk for SICH
      but have lower rates of good outcomes. In this patient group, successful
      revascularization appears to be associated with improved clinical outcomes and
      lower mortality.

PMID- 19095995
TI  - When disclosures are more interesting than the evidence.

PMID- 19095996
TI  - Leukocyte cathepsin S is a potent regulator of both cell and matrix turnover in
      advanced atherosclerosis.
AB  - OBJECTIVE: A dysbalance of proteases and their inhibitors is instrumental in
      remodeling of atherosclerotic plaques. One of the proteases implicated in matrix
      degradation is cathepsin-S (CatS). To address its role in advanced lesion
      composition, we generated chimeric LDLr(-/-) mice deficient in leukocyte CatS by
      transplantation with CatS(-/-)xLDLr(-/-) or with LDLr(-/-) bone marrow and
      administered a high-fat diet. METHODS AND RESULTS: No difference in aortic root
      lesion size could be detected between CatS(+/+) and CatS(-/-) chimeras. However,
      leukocyte CatS deficiency markedly changed plaque morphology and led to a
      dramatic reduction in necrotic core area by 77% and an abundance of large foam
      cells. Plaques of CatS(-/-) chimeras contained 17% more macrophages, 62% less
      SMCs, and 33% less intimal collagen. The latter two could be explained by a
      reduced number of elastic lamina fractures. Moreover, macrophage apoptosis was
      reduced by 60% with CatS deficiency. In vitro, CatS was found to be involved in
      cholesterol metabolism and in macrophage apoptosis in a collagen and fibronectin
      matrix. CONCLUSIONS: Leukocyte CatS deficiency results in considerably altered
      plaque morphology, with smaller necrotic cores, reduced apoptosis, and decreased
      SMC content and collagen deposition and may thus be critical in plaque stability.

PMID- 19095997
TI  - Despite antiatherogenic metabolic characteristics, SCD1-deficient mice have
      increased inflammation and atherosclerosis.
AB  - OBJECTIVE: Absence of stearoyl-CoA desaturase-1 (SCD1) in mice reduces plasma
      triglycerides and provides protection from obesity and insulin resistance, which
      would be predicted to be associated with reduced susceptibility to
      atherosclerosis. The aim of this study was to determine the effect of SCD1
      deficiency on atherosclerosis. METHODS AND RESULTS: Despite an antiatherogenic
      metabolic profile, SCD1 deficiency increases atherosclerosis in hyperlipidemic
      low-density lipoprotein receptor (LDLR)-deficient mice challenged with a Western
      diet. Lesion area at the aortic root is significantly increased in males and
      females in two models of SCD1 deficiency. Inflammatory changes are evident in the
      skin of these mice, including increased intercellular adhesion molecule (ICAM)-1
      and ulcerative dermatitis. Increases in ICAM-1 and interleukin-6 are also evident
      in plasma of SCD1-deficient mice. HDL particles demonstrate changes associated
      with inflammation, including decreased plasma apoA-II and apoA-I and paraoxonase
      1 and increased plasma serum amyloid A. Lipopolysaccharide-induced inflammatory
      response and cholesterol efflux are not altered in SCD1-deficient macrophages. In
      addition, when SCD1 deficiency is limited to bone marrow-derived cells, lesion
      size is not altered in LDLR-deficient mice. CONCLUSIONS: These studies reinforce
      the crucial role of chronic inflammation in promoting atherosclerosis, even in
      the presence of antiatherogenic biochemical and metabolic characteristics.

PMID- 19095998
TI  - Endothelial nitric oxide synthase inhibits G12/13 and rho-kinase activated by the
      angiotensin II type-1 receptor: implication in vascular migration.
AB  - BACKGROUND: Although, endothelial nitric oxide (NO) synthase (eNOS) is believed
      to antagonize vascular remodeling induced by the angiotensin II (AngII) type-1
      receptor, the exact signaling mechanism remains unclear. METHODS AND RESULTS: By
      expressing eNOS to vascular smooth muscle cells (VSMCs) via adenovirus, we
      investigated a signal transduction mechanism of the eNOS gene transfer in
      preventing vascular remodeling induced by AngII. We found marked inhibition of
      AngII-induced Rho/Rho-kinase activation and subsequent VSMC migration by eNOS
      gene transfer whereas G(q)-dependent transactivation of the epidermal growth
      factor receptor by AngII remains intact. This could be explained by the specific
      inhibition of G(12/13) activation by eNOS-mediated G(12/13) phosphorylation.
      CONCLUSIONS: The eNOS/NO cascade specifically targets the Rho/Rho-kinase system
      via inhibition of G(12/13) to prevent vascular migration induced by AngII,
      representing a novel signal cross-talk in cardiovascular protection by NO.

PMID- 19096000
TI  - Certain progestins prevent the enhancing effect of 17beta-estradiol on NO
      mediated inhibition of platelet aggregation by endothelial cells.
AB  - OBJECTIVE: Estro-progestin treatments have been associated with an increased risk
      of thromboembolic events in postmenopausal women. This study examined whether
      progestins affect the stimulatory effect of estrogens on the endothelial
      formation of nitric oxide (NO), a potent antithrombotic factor. METHODS AND
      RESULTS: Experiments were performed with human endothelial cells. Endothelial NO
      synthase (eNOS) and GTP cyclohydrolase I (GTPCH I) mRNA expression was assessed
      by RT-PCR, eNOS protein by Western blotting, NO formation by electron spin
      resonance spectroscopy, and platelet aggregation by an aggregometer.
      Medroxyprogesterone acetate (MPA), progesterone, levonorgestrel, and nomegestrol
      acetate prevented the 17beta-estradiol (17beta-E)-induced expression of eNOS mRNA
      and protein. MPA and progesterone reduced the 17beta-E-induced formation of NO
      and potentiation of the inhibitory effect of endothelial cells on platelet
      aggregation whereas levonorgestrel and nomegestrol acetate were without effect.
      Moreover, MPA and progesterone prevented the 17beta-E-induced expression of GTPCH
      I mRNA. Mifepristone, a glucocorticoid and progesterone receptor antagonist, and
      L-sepiapterin prevented the inhibitory effect of MPA and progesterone on platelet
      aggregation. CONCLUSIONS: Certain progestins, including MPA, attenuate the 17beta
      E-induced NO-mediated inhibition of platelet aggregation by endothelial cells
      through preventing both eNOS and GTPCH I expression most likely via activation of
      glucocorticoid receptors.

PMID- 19095999
TI  - Role of Src tyrosine kinase in the atherogenic effects of the 12/15-lipoxygenase
      pathway in vascular smooth muscle cells.
AB  - OBJECTIVE: The 12/15-Lipoxygenase (12/15-LO) and its metabolite 12(S)
      Hydroxyeicosatetraenoic acid [12(S)-HETE] mediate proatherogenic responses in
      vascular smooth muscle cells (VSMCs). We examined the role of the nonreceptor
      tyrosine kinase Src in the signaling and epigenetic chromatin mechanisms involved
      in these processes. METHODS AND RESULTS: Rat VSMCs (RVSMCs) were stimulated with
      12(S)-HETE (0.1 micromol/L) in the presence or absence of the Src inhibitor PP2
      (10 micromol/L). Src activation and downstream signaling events including
      inflammatory gene expression and chromatin histone H3-Lys-9/14 acetylation were
      examined by immunoblotting, RT-PCR, and chromatin immunoprecipitation assays,
      respectively. 12(S)-HETE significantly activated Src, focal adhesion kinase, Akt,
      p38MAPK, and CREB. Expression of monocyte chemoattractant protein-1 and
      interleukin-6 genes and histone H3-Lys-9/14 acetylation on their promoters were
      also increased by 12(S)-HETE. PP2 inhibited these responses as well as 12(S)-HETE
      induced VSMC migration. Furthermore, dominant negative mutants of Src, CREB, and
      a histone acetyltransferase p300 significantly blocked 12(S)-HETE-induced
      inflammatory gene expression. In addition, growth factor induced Src signaling
      and downstream events including H3-Lys-9/14 acetylation and migration were
      significantly attenuated in VSMCs derived from 12/15-LO(-/-) mice relative to WT.
      CONCLUSIONS: Src kinase signaling plays a central role in the proatherogenic
      responses mediated by 12/15-LO and its oxidized lipid metabolite 12(S)-HETE in
      VSMCs.

PMID- 19096001
TI  - Downregulation of platelet responsiveness upon contact with LDL by the protein
      tyrosine phosphatases SHP-1 and SHP-2.
AB  - OBJECTIVE: The sensitivity of platelets to aggregating agents increases when low
      density lipoprotein (LDL) binds to apolipoprotein E receptor 2' (apoER2'),
      triggering activation of p38MAPK and formation of thromboxane A2. LDL signaling
      is terminated by PECAM-1 through recruitment and activation of the Ser/Thr
      protein phosphatase PP2A, but platelets remain unresponsive to LDL when PECAM-1
      activation disappears. We report a second mechanism that halts LDL signaling and
      in addition lowers platelet responsiveness to aggregating agents. METHODS AND
      RESULTS: After a first stimulation with LDL, platelets remain unresponsive to LDL
      for 60 minutes, despite normal apoER2' activation by a second dose of LDL. A
      possible cause is persistent activation of the tyrosine phosphatases SHP-1 and
      SHP-2, which may not only block a second activation of p38MAPK, PECAM-1, and PP2A
      by LDL but also seem to reduce aggregation by TRAP, collagen, and ADP.
      CONCLUSION: These findings reveal that p38MAPK phosphorylation and platelet
      activation by LDL are suppressed by two mechanisms: (1) short activation of PECAM
      1/PP2A, and (2) prolonged activation of SHP-1 and SHP-2. Activation of SHP-1 and
      SHP-2 is accompanied by reduced responsiveness to aggregating agents, which--if
      present in vivo--would make LDL an aggregation inhibitor during prolonged contact
      with platelets.

PMID- 19096002
TI  - C-reactive protein levels, haplotypes, and the risk of incident chronic
      obstructive pulmonary disease.
AB  - RATIONALE: Chronic obstructive pulmonary disease (COPD) is characterized by
      substantial chronic inflammation in the pulmonary compartment as well as in the
      systemic circulation. OBJECTIVES: To investigate potentially causal association,
      we examined whether serum levels of high-sensitivity C-reactive protein (hsCRP)
      and variations in the CRP gene are associated with the risk of developing COPD.
      METHODS: This study is part of the Rotterdam Study, a prospective population
      based cohort study among subjects aged 55 years or older. At baseline, 6,836
      subjects without COPD had a blood sample available for assessment of hsCRP serum
      levels and haplotypes of the CRP gene. We analyzed the association between hsCRP
      levels, CRP gene haplotypes, and incident COPD with Cox proportional hazard
      models, adjusted for age, sex, and other confounders. MEASUREMENTS AND MAIN
      RESULTS: High levels of hsCRP (>3 mg/L) were associated with a significantly
      increased risk of incident COPD (hazard ratio [HR], 1.7; 95% confidence interval
      [CI], 1.16-2.49) compared with persons with low levels (<1 mg/L). The risk
      remained increased after adjusting for potential confounders and introducing a
      latency period of 3 years. The risk was most pronounced in former smokers (HR,
      2.2; 95% CI, 1.12-3.74). hsCRP was not a risk factor in never smokers. No CRP
      single nucleotide polymorphism or haplotype was associated with a significantly
      increased or decreased COPD risk. CONCLUSIONS: Increased hsCRP levels are
      predictive for the occurrence of COPD in smokers. However, haplotypes of the CRP
      gene, which influence hsCRP levels, are not associated with an altered risk of
      developing COPD.

PMID- 19096003
TI  - CD14 and toll-like receptor gene polymorphisms, country living, and asthma in
      adults.
AB  - RATIONALE: It has been shown that country living protects against asthma, which
      may be explained by microbial exposures. OBJECTIVES: To study whether single
      nucleotide polymorphisms (SNPs) in CD14 and Toll-like receptor (TLR) 2, TLR4 and
      TLR9 genes are associated with asthma in adults, and whether these SNPs modify
      associations between country living and asthma. METHODS: Twenty-five SNPs in
      CD14, TLR2, TLR4, and TLR9 genes were genotyped in adult subjects from the French
      Epidemiological study on the Genetics and Environment of Asthma, Bronchial
      Hyperresponsiveness, and Atopy (EGEA). We conducted a case-control analysis on
      unrelated subjects (239 with asthma and 596 without asthma), and a family-based
      association test (FBAT) in 192 families ascertained through probands with asthma.
      MEASUREMENTS AND MAIN RESULTS: The TLR2/+596 C allele was associated with an
      increased risk for asthma in both case-control and family-based analyses (under a
      dominant model, odds ratio [OR] 1.91 and 95% confidence interval [CI] 1.34-2.72,
      P = 0.0003; Z statistics from FBAT = 2.48, P = 0.01). In skin prick test (SPT)
      positive subjects, the CD14/-260 C allele was negatively associated with asthma
      (additive model, OR 0.66; CI 0.48-0.91). Significant gene-environment
      interactions between variation in CD14 and TLR genes and country living during
      childhood were found for ten SNPs. In SPT positive subjects carrying CD14/-260
      CC, country living protected against asthma (OR, 0.32; 95% CI, 0.12-0.85),
      whereas country living was not associated with asthma in subjects who were atopic
      and carrying CD14/-260 T (OR, 1.11; 95% CI, 0.65-1.90) (gene-environment
      interaction, P < 0.05). CONCLUSIONS: TLR2 and CD14 SNPs were associated with
      asthma and atopic asthma respectively. In addition, CD14, TLR2, TLR4, and TLR9
      SNPs modified associations between country living and asthma.

PMID- 19096004
TI  - Gastroesophageal reflux and pulmonary fibrosis in scleroderma: a study using pH
      impedance monitoring.
AB  - RATIONALE: Interstitial lung disease (ILD) in patients with systemic sclerosis
      (SSc) is associated with increased morbidity and mortality. Gastroesophageal
      reflux (GER) is considered a contributing factor in the pathogenesis of ILD.
      OBJECTIVES: To characterize GER (acid and nonacid) in patients with SSc with and
      without ILD. METHODS: Patients with SSc underwent pulmonary high-resolution
      computer tomography (HRCT) scan and 24-hour impedance-pH monitoring off-proton
      pump inhibitor therapy. The presence of pulmonary fibrosis was assessed using
      validated HRCT-scores. Reflux monitoring parameters included number of acid and
      nonacid reflux episodes, proximal migration of the refluxate, and distal
      esophageal acid exposure. Unless otherwise specified, data are presented as
      median (25th-75th percentile). MEASUREMENTS AND MAIN RESULTS: Forty consecutive
      patients with SSc (35 female; mean age, 53 yr; range, 24-71; 15 patients with
      diffuse and 25 with limited SSc) were investigated; 18 (45%) patients with SSc
      had pulmonary fibrosis (HRCT score >or= 7). Patients with SSc with ILD had higher
      (P < 0.01) esophageal acid exposure (10.3 [7.5-15] vs. 5.2 [1.5-11]), higher (P <
      0.01) number of acid (41 [31-58] vs. 19 [10-23]) and nonacid (25 [20-35] vs. 17
      [11-19]) reflux episodes, and higher (P < 0.01) number of reflux episodes
      reaching the proximal esophagus (42.5 [31-54] vs. 15 [8-22]) compared with
      patients with SSc with normal HRCT scores. Pulmonary fibrosis scores (HRCT score)
      correlated well with the number of reflux episodes in the distal (r(2) = 0.637)
      and proximal (r(2) = 0.644) esophagus. CONCLUSIONS: Patients with SSc with ILD
      have more severe reflux (i.e., more reflux episodes and more reflux reaching the
      proximal esophagus). Whether or not the development of ILD in patients with SSc
      can be prevented by reflux-reducing treatments needs to be investigated.

PMID- 19096005
TI  - Variants in TGFB1, dust mite exposure, and disease severity in children with
      asthma.
AB  - RATIONALE: Polymorphisms in the gene for transforming growth factor-beta1 (TGFB1)
      have been associated with asthma, but not with airway responsiveness or disease
      exacerbations in subjects with asthma. OBJECTIVES: To test for association
      between single nucleotide polymorphisms (SNPs) in TGFB1 and markers of asthma
      severity in childhood. METHODS: We tested for the association between nine SNPs
      in TGFB1 and indicators of asthma severity (lung function, airway responsiveness,
      and disease exacerbations) in two cohorts: 416 Costa Rican parent-child trios and
      465 families of non-Hispanic white children in the Childhood Asthma Management
      Program (CAMP). We also tested for the interaction between these polymorphisms
      and exposure to dust mite allergen on asthma severity. MEASUREMENTS AND MAIN
      RESULTS: The A allele of promoter SNP rs2241712 was associated with increased
      airway responsiveness in Costa Rica (P = 0.0006) and CAMP (P = 0.005), and the C
      allele of an SNP in the promoter region (rs1800469) was associated with increased
      airway responsiveness in both cohorts (P <or= 0.01). Dust mite exposure modified
      the effect of the C allele of exonic SNP rs1800471 on airway responsiveness (P =
      0.03 for interactions in both cohorts). The T allele of a coding SNP (rs1982073)
      was associated with a reduced risk of asthma exacerbations in Costa Rica (P =
      0.009) and CAMP (P = 0.005). Dust mite exposure also significantly modified the
      effect of the A allele of the promoter SNP rs2241712 on asthma exacerbations in
      both cohorts. CONCLUSIONS: SNPs in TGFB1 are associated with airway
      responsiveness and disease exacerbations in children with asthma. Moreover, dust
      mite exposure may modify the effect of TGFB1 SNPs on airway responsiveness and
      asthma exacerbations.

PMID- 19096006
TI  - Fragile histidine triad gene inactivation in lung cancer: the European Early Lung
      Cancer project.
AB  - RATIONALE: Fragile histidine triad (FHIT) is a tumor suppressor gene involved in
      the pathogenesis of lung cancer. OBJECTIVES: The purpose of this study was to
      investigate the different molecular alterations leading to the inactivation of
      FHIT gene function and to validate their use as biomarkers of risk for
      progression of the disease in patients belonging to the multicentric European
      study for the Early detection of Lung Cancer (EUELC) who were resected for early
      stage lung tumors. METHODS: FHIT immunostaining was performed on 305 tumor
      samples. The methylation status of FHIT promoter was assessed by nested
      methylation-specific polymerase chain reaction (MSP-PCR) in 232 tumor and 225
      normal lung samples of which a subset of 187 patients had available normal/tumor
      DNA pairs. Loss of heterozygosity (LOH) at the FHIT locus was analyzed in 202
      informative cases by D3S1300 and D3S1234 microsatellite markers. MEASUREMENTS AND
      MAIN RESULTS: Lost or reduced FHIT expression was found in 36.7 and 75.7% of the
      tumor samples, respectively. Methylation of the FHIT promoter was found in 36.7%
      of tumor and 32.7% of normal lung samples, whereas LOH was detected in 61.9% of
      the tumors. A strong association with complete loss of FHIT expression was
      present when methylation and LOH were analyzed together (P = 0.0064). Loss of
      FHIT protein expression was significantly more frequent in squamous cell
      carcinoma histotype (P < 0.0001) and in smokers (P = 0.008). FHIT methylation in
      normal lung was associated with an increased risk of progressive disease (OR,
      2.27; P = 0.0415). CONCLUSIONS: Our results indicate that different molecular
      mechanisms interplay to inactivate FHIT expression and support the proposition
      that FHIT methylation in normal lung tissue could represent a prognostic marker
      for progressive disease.

PMID- 19096007
TI  - Alveolar type II epithelial cells present antigen to CD4(+) T cells and induce
      Foxp3(+) regulatory T cells.
AB  - RATIONALE: Although the contribution of alveolar type II epithelial cells
      (AECIIs) in respiratory immunity has become increasingly appreciated, their
      precise function in the induction and regulation of T-cell reactivity to self
      antigen remains poorly understood. OBJECTIVES: To investigate the role of AECII
      in the initiation of T-cell reactivity to alveolar self-antigen, and to clarify
      their function in the peripheral induction of Foxp3(+) regulatory CD4(+) T cells.
      METHODS: To dissect the complex cellular and molecular functions of AECIIs in
      lung inflammation and immune regulation, we use a transgenic mouse model for
      CD4(+) T-cell-mediated pulmonary inflammation. MEASUREMENTS AND MAIN RESULTS:
      Here we report that AECIIs present endogenously expressed antigen on major
      histocompatibility complex class II molecules to CD4(+) T cells. Epithelial
      antigen display was sufficient to induce primary T-cell activation and pulmonary
      inflammation. Upon inflammation, AECIIs induce the differentiation of Foxp3(+)
      regulatory T cells by a mechanism involving antiproliferative soluble factors,
      including transforming growth factor (TGF)-beta. Whereas, in acute inflammation,
      TGF-beta appears to be the dominant factor to induce regulatory T cells, other
      AECII-derived factors can substitute for and/or synergize with TGF-beta in
      chronic pulmonary inflammations. CONCLUSIONS: AECIIs are capable of priming naive
      CD4(+) T cells, demonstrating an active participation of these cells in
      respiratory immunity. Moreover, AECIIs display as yet unrecognized functions in
      balancing inflammatory and regulatory T-cell responses in the lung by connecting
      innate and adaptive immune mechanisms to establish peripheral T-cell tolerance to
      respiratory self-antigen.

PMID- 19096008
TI  - Primary central nervous system lymphoma: tumor-related clones exist in the blood
      and bone marrow with evidence for separate development.
AB  - Primary central nervous system (CNS) lymphoma is an aggressive B-cell tumor that
      is defined clinically by the absence of systemic disease. We have used
      immunoglobulin variable (V)-gene analysis to identify tumor cells at the CNS site
      in 12 cases and to probe the involvement of peripheral tissues in 3 patients.
      Clonal tracking revealed tumor cells in the bone marrow and/or blood for 3 of 3
      cases, with evidence for increased V-gene mutational activity at peripheral
      sites. In 2 of 3 cases, intraclonal variant analysis revealed identity with the
      brain biopsy but detected additional variants unique to extracerebral sites.
      These findings suggest that peripheral tumor cells can undergo separate
      development locally with no reentry into the brain. Primary CNS lymphoma appears
      to have both CNS-specific and systemic components with limited interchange. The
      more malignant behavior of tumor cells in the CNS suggests either a local
      environmental influence or a less malignant phenotype of the peripheral clone.

PMID- 19096009
TI  - Specific activation of microRNA106b enables the p73 apoptotic response in chronic
      lymphocytic leukemia by targeting the ubiquitin ligase Itch for degradation.
AB  - Chronic lymphocytic leukemia (CLL) is characterized by cells that exhibit
      dysfunctional apoptosis. Here, we show that deacetylase inhibition led to the
      E2F1- and myc-mediated transcriptional activation of the microRNA miR106b in
      primary CLL cells. Induction of miR106b was associated with a down-regulation in
      the levels of the E3-ubiquitin ligase Itch. Decreases in Itch protein levels were
      associated with a reciprocal accumulation of its proapoptotic substrate, TAp73
      (p73), and induction of p53 up-regulated modulator of apoptosis (PUMA) mRNA and
      protein. This event was accompanied by mitochondrial dysfunction, processing of
      caspase-9, and apoptosis of CLL cells. Ectopic expression of miR106b in CLL cells
      demonstrated that Itch was a direct target of miR106b such that miR106b-induced
      decreases in Itch resulted in an accumulation of p73. Thus, our results identify
      a novel regulatory mechanism wherein microRNA regulate cell survival by mediating
      the posttranscriptional down-regulation of an ubiquitin ligase, leading to the
      induction of a proapoptotic regulator in malignant cells. Silencing of miRNA
      expression in CLL may selectively suppress proapoptotic pathways, providing such
      tumors with a survival advantage. Consequently, chemotherapeutic drugs that
      activate miR106b could initiate a p53-independent mechanism that targets CLL
      cells.

PMID- 19096010
TI  - The endothelial antigen ESAM marks primitive hematopoietic progenitors throughout
      life in mice.
AB  - Although recent advances have enabled hematopoietic stem cells (HSCs) to be
      enriched to near purity, more information about their characteristics will
      improve our understanding of their development and stage-related functions. Here,
      using microarray technology, we identified endothelial cell-selective adhesion
      molecule (ESAM) as a novel marker for murine HSCs in fetal liver. Esam was
      expressed at high levels within a Rag1(-) c-kit(Hi) Sca1(+) HSC-enriched
      fraction, but sharply down-regulated with activation of the Rag1 locus, a valid
      marker for the most primitive lymphoid progenitors in E14.5 liver. The HSC
      enriched fraction could be subdivided into 2 on the basis of ESAM levels. Among
      endothelial antigens on hematopoietic progenitors, ESAM expression showed
      intimate correlation with HSC activity. The ESAM(Hi) population was highly
      enriched for multipotent myeloid-erythroid progenitors and primitive progenitors
      with lymphopoietic activity, and exclusively reconstituted long-term
      lymphohematopoiesis in lethally irradiated recipients. Tie2(+) c-kit(+)
      lymphohematopoietic cells in the E9.5-10.5 aorta-gonad-mesonephros region also
      expressed high levels of ESAM. Furthermore, ESAM was detected on primitive
      hematopoietic progenitors in adult bone marrow. Interestingly, ESAM expression in
      the HSC-enriched fraction was up-regulated in aged mice. We conclude that ESAM
      marks HSC in murine fetal liver and will facilitate studies of hematopoiesis
      throughout life.

PMID- 19096011
TI  - Identification of a potent natural triterpenoid inhibitor of proteosome
      chymotrypsin-like activity and NF-kappaB with antimyeloma activity in vitro and
      in vivo.
AB  - As multiple myeloma tumors universally dysregulate cyclin D genes we conducted
      high-throughput chemical library screens for compounds that induce suppression of
      cyclin D2 promoter transcription. The top-ranked compound was a natural
      triterpenoid, pristimerin. Strikingly, the early transcriptional response of
      cells treated with pristimerin closely resembles cellular responses elicited by
      proteosome inhibitors, with rapid induction of heat shock proteins, activating
      transcription factor 3 (ATF3), and CHOP. Enzymatic assays and immunoblotting
      confirm that pristimerin rapidly (< 90 minutes) and specifically inhibits
      chymotrypsin-like proteosome activity at low concentrations (< 100 nM) and causes
      accumulation of cellular ubiquitinated proteins. Notably, cytotoxic triterpenoids
      including pristimerin inhibit NF-kappaB activation via inhibition of IKK alpha or
      IKK beta, whereas proteosome inhibitors instead suppress NF-kappaB function by
      impairing degradation of ubiquitinated I kappaB. By inhibiting both IKK and the
      proteosome, pristimerin causes overt suppression of constitutive NF-kappaB
      activity in myeloma cells that may mediate its suppression of cyclin D. Multiple
      myeloma is exquisitely sensitive to proteosome or NF-kappaB pathway inhibition.
      Consistent with this, pristimerin is potently and selectively lethal to primary
      myeloma cells (IC(50) < 100 nM), inhibits xenografted plasmacytoma tumors in
      mice, and is synergistically cytotoxic with bortezomib--providing the rationale
      for pharmaceutical development of triterpenoid dual-function proteosome/NF-kappaB
      inhibitors as therapeutics for human multiple myeloma and related malignancies.

PMID- 19096012
TI  - Molecular profiling of classical Hodgkin lymphoma tissues uncovers variations in
      the tumor microenvironment and correlations with EBV infection and outcome.
AB  - The outcome of classical Hodgkin lymphoma (cHL) patients may be related to the
      tumor microenvironment, which in turn may be influenced by Epstein-Barr virus
      (EBV) infection. To characterize the cHL microenvironment, a set of 63 cHL tissue
      samples was profiled using DNA microarrays. Their gene expression profile
      differed from that of histiocyte T cell-rich B-cell lymphoma (H/TCRBCL) samples
      that were used as controls, mainly due to high expression of PDCD1/PD-1 in
      H/TCRBCL. EBV(+) cHL tissues could be distinguished from EBV(-) samples by a gene
      signature characteristic of Th1 and antiviral responses. Samples from cHL
      patients with favorable outcome overexpressed genes specific for B cells and
      genes involved in apoptotic pathways. An independent set of 146 cHL samples was
      analyzed using immunohistochemistry. It showed a significant adverse value in
      case of high percentage of either TIA-1(+)-reactive cells or topoisomerase-2(+)
      tumor cells, whereas high numbers of BCL11A(+), FOXP3(+), or CD20(+) reactive
      cells had a favorable influence. Our results suggest an antitumoral role for B
      cells in the cHL microenvironment and a stronger stromal influence of the PD1
      pathway in H/TCRBCL than cHL. The observation of Th1/ antiviral response in
      EBV(+) cHL tissues provides a basis for novel treatment strategies.

PMID- 19096013
TI  - Of mice and men: an open-label pilot study for treatment of immune
      thrombocytopenic purpura by an inhibitor of Syk.
AB  - To determine whether inhibition of Syk would be useful in FcgammaR-dependent
      cytopenias such as immune thrombocytopenic purpura (ITP) or autoimmune hemolytic
      anemia, mouse models were used to evaluate efficacy of R406, an inhibitor of Syk
      function, in treating cytopenia. Both disease models responded favorably to
      treatment, with amelioration of ITP being more dramatic. Thus, phase 2 clinical
      trial was initiated to study the effects of Syk inhibition in humans with ITP.
      Sixteen adults with chronic ITP were entered into an open-label, single-arm
      cohort dose-escalation trial beginning with 75 mg and escalating as high as 175
      mg twice daily. Doses were increased until a persistent response was seen,
      toxicity occurred, or 175 mg twice daily was reached. Eight patients achieved
      persistent responses with platelet counts greater than 50 x 10(9)/L (50 000
      mm(3)) on more than 67% (actually 95%) of their study visits, including 3 who had
      not persistently responded to thrombopoietic agents. Four others had nonsustained
      responses. Mean peak platelet count exceeded 100 x 10(9)/L (100 000 mm(3)) in
      these 12 patients. Toxicity was primarily GI-related with diarrhea (urgency) and
      vomiting; 2 patients had transaminitis. In conclusion, inhibition of Syk was an
      efficacious means of increasing and maintaining the platelet count in half the
      patients with chronic refractory ITP. (ClinicalTrials.gov, no. NCT00706342).

PMID- 19096014
TI  - Hypomethylating drugs convert HA-1-negative solid tumors into targets for stem
      cell-based immunotherapy.
AB  - Clinical responses of solid tumors after allogeneic human leukocyte antigen
      matched stem cell transplantation (SCT) often coincide with severe graft-versus
      host disease (GVHD). Targeting minor histocompatibility antigens (mHags) with
      hematopoiesis- and cancer-restricted expression, for example, HA-1, may allow
      boosting the antitumor effect of allogeneic SCT without risking severe GVHD. The
      mHag HA-1 is aberrantly expressed in cancers of most entities. However, an
      estimated 30% to 40% of solid tumors do not express HA-1 (ie, are HA-1(neg)) and
      cannot be targeted by HA-1-specific immunotherapy. Here, we investigated the
      transcriptional regulation of HA-1 gene expression in cancer. We found that DNA
      hypermethylation in the HA-1 promoter region is closely associated with the
      absence of HA-1 gene expression in solid tumor cell lines. Moreover, we detected
      HA-1 promoter hypermethylation in primary cancers. The hypomethylating agent 5
      aza-2'-deoxycytidine induced HA-1 expression only in HA-1(neg) tumor cells and
      sensitized them for recognition by HA-1-specific cytotoxic T lymphocytes.
      Contrarily, the histone deacetylation inhibitor trichostatin A induced HA-1
      expression both in some HA-1(neg) tumor cell lines and in normal nonhematopoietic
      cells. Our data suggest that promoter hypermethylation contributes to the HA-1
      gene regulation in tumors. Hypomethylating drugs might extend the safe
      applicability of HA-1 as an immunotherapeutic target on solid tumors after
      allogeneic SCT.

PMID- 19096015
TI  - Molecular genetics of alcohol-related brain damage.
AB  - AIMS: In the scientific literature it has been repeatedly hypothesized that there
      is a heritable susceptibility to thiamine deficiency comparable to other
      hereditary metabolic disorders. The aim of this paper is to review the most
      recent knowledge on the genetic susceptibility to the development of alcohol
      related Wernicke-Korsakoff syndrome (WKS). METHODS: A literature review was
      carried out looking at the molecular genetics studies performed in alcohol
      dependent patients affected by WKS. RESULTS: A genetic component in the
      pathogenesis of WKS has been postulated since the late seventies. Since then,
      very few genetic studies have been carried out on candidate genes such as
      thiamine-dependent enzymes, alcohol-metabolizing enzymes and GABA receptors. The
      findings are controversial and not conclusive. Several authors reported the
      important role of the thiamine transporters in the pathogenesis of the thiamine
      deficiency disorders. Our findings on SLC19A2 and SLC19A3 suggest a potential
      role of these two genes in the pathophysiology of alcohol-related thiamine
      deficiency but further studies need to be carried out. CONCLUSIONS: The WKS may
      be a very complex, multifactorial disorder where the interaction of multiple
      genes and environment plays an important role in the pathogenesis. However, it is
      still plausible that megaphenic gene effects are responsible for WKS
      susceptibility and the thiamine transport genes are good candidates for having
      such a role. Further genetic studies are definitely needed to investigate the
      association with candidate genes or linkage with hot spot areas.

PMID- 19096016
TI  - Treating low back pain: Alexander technique and exercise, antibiotics (!) and
      Paul Hodges on dynamic stability.

PMID- 19096017
TI  - Transversus abdominis: a different view of the elephant.

PMID- 19096018
TI  - Birth date and birth place effects in National Hockey League draftees 2000-2005:
      comments on Baker and Logan (2007).

PMID- 19096019
TI  - Randomised controlled trial of Alexander technique lessons, exercise, and massage
      (ATEAM) for chronic and recurrent back pain.
AB  - OBJECTIVE: To determine the effectiveness of lessons in the Alexander technique,
      massage therapy, and advice from a doctor to take exercise (exercise
      prescription) along with nurse delivered behavioural counselling for patients
      with chronic or recurrent back pain. DESIGN: Factorial randomised trial. Setting
      64 general practices in England. PARTICIPANTS: 579 patients with chronic or
      recurrent low back pain; 144 were randomised to normal care, 147 to massage, 144
      to six Alexander technique lessons, and 144 to 24 Alexander technique lessons;
      half of each of these groups were randomised to exercise prescription.
      INTERVENTIONS: Normal care (control), six sessions of massage, six or 24 lessons
      on the Alexander technique, and prescription for exercise from a doctor with
      nurse delivered behavioural counselling. MAIN OUTCOME MEASURES: Roland Morris
      disability score (number of activities impaired by pain) and number of days in
      pain. RESULTS: Exercise and lessons in the Alexander technique, but not massage,
      remained effective at one year (compared with control Roland disability score
      8.1: massage -0.58, 95% confidence interval -1.94 to 0.77, six lessons -1.40, 
      2.77 to -0.03, 24 lessons -3.4, -4.76 to -2.03, and exercise -1.29, -2.25 to 
      0.34). Exercise after six lessons achieved 72% of the effect of 24 lessons alone
      (Roland disability score -2.98 and -4.14, respectively). Number of days with back
      pain in the past four weeks were lower after lessons (compared with control
      median 21 days: 24 lessons -18, six lessons -10, massage -7) and quality of life
      improved significantly. No significant harms were reported. CONCLUSIONS: One to
      one lessons in the Alexander technique from registered teachers have long term
      benefits for patients with chronic back pain. Six lessons followed by exercise
      prescription were nearly as effective as 24 lessons.

PMID- 19096020
TI  - Cricket ball injury: a cause of symptomatic muscle hernia of the leg.
AB  - A case of symptomatic muscle hernia of the leg in a provincial cricketer caused
      by a cricket ball injury is presented. It was diagnosed clinically and treated
      with a limited fasciotomy. However, delay in the diagnosis and treatment ended
      the professional career of the player. An awareness of the condition and a high
      index of suspicion are required to treat this condition in time.

PMID- 19096022
TI  - Increased Ca2+ sensitivity of the ryanodine receptor mutant RyR2R4496C underlies
      catecholaminergic polymorphic ventricular tachycardia.
AB  - Cardiac ryanodine receptor (RyR2) mutations are associated with autosomal
      dominant catecholaminergic polymorphic ventricular tachycardia, suggesting that
      alterations in Ca(2+) handling underlie this disease. Here we analyze the
      underlying Ca(2+) release defect that leads to arrhythmia in cardiomyocytes
      isolated from heterozygous knock-in mice carrying the RyR2(R4496C) mutation.
      RyR2(R4496C-/-) littermates (wild type) were used as controls. [Ca(2+)](i)
      transients were obtained by field stimulation in fluo-3-loaded cardiomyocytes and
      viewed using confocal microscopy. In our basal recording conditions (2-Hz
      stimulation rate), [Ca(2+)](i) transients and sarcoplasmic reticulum Ca(2+) load
      were similar in wild-type and RyR2(R4496C) cells. However, paced RyR2(R4496C)
      ventricular myocytes presented abnormal Ca(2+) release during the diastolic
      period, viewed as Ca(2+) waves, consistent with the occurrence of delayed
      afterdepolarizations. The occurrence of this abnormal Ca(2+) release was enhanced
      at faster stimulation rates and by beta-adrenergic stimulation, which also
      induced triggered activity. Spontaneous Ca(2+) sparks were more frequent in
      RyR2(R4496C) myocytes, indicating increased RyR2(R4496C) activity. When
      permeabilized cells were exposed to different cytosolic [Ca(2+)](i), RyR2(R4496C)
      showed a dramatic increase in Ca(2+) sensitivity. Isoproterenol increased
      [Ca(2+)](i) transient amplitude and Ca(2+) spark frequency to the same extent in
      wild-type and RyR2(R4496C) cells, indicating that the beta-adrenergic sensitivity
      of RyR2(R4496C) cells remained unaltered. This effect was independent of protein
      expression variations because no difference was found in the total or
      phosphorylated RyR2 expression levels. In conclusion, the arrhythmogenic
      potential of the RyR2(R4496C) mutation is attributable to the increased Ca(2+)
      sensitivity of RyR2(R4496C), which induces diastolic Ca(2+) release and lowers
      the threshold for triggered activity.

PMID- 19096023
TI  - Activation of AMP-activated protein kinase by metformin improves left ventricular
      function and survival in heart failure.
AB  - Clinical studies have reported that the widely used antihyperglycemic drug
      metformin significantly reduces cardiac risk factors and improves clinical
      outcomes in patients with heart failure. The mechanisms by which metformin exerts
      these cardioprotective effects remain unclear and may be independent of
      antihyperglycemic effects. We tested the hypothesis that chronic activation of
      AMP-activated protein kinase (AMPK) with low-dose metformin exerts beneficial
      effects on cardiac function and survival in in vivo murine models of heart
      failure. Mice were subjected to permanent left coronary artery occlusion or to 60
      minutes left coronary artery occlusion followed by reperfusion for 4 weeks. High
      resolution, 2D echocardiography was performed at baseline and 4 weeks after
      myocardial infarction to assess left ventricular dimensions and function.
      Metformin (125 microg/kg) administered to mice at ischemia and then daily
      improved survival by 47% (P<0.05 versus vehicle) at 4 weeks following permanent
      left coronary artery occlusion. Additionally, metformin given at reperfusion and
      then daily preserved left ventricular dimensions and left ventricular ejection
      fraction (P<0.01 versus vehicle) at 4 weeks. The improvement in cardiac structure
      and function was associated with increases in AMPK and endothelial nitric oxide
      synthase (eNOS) phosphorylation, as well as increased peroxisome proliferator
      activated receptor-gamma coactivator (PGC)-1alpha expression in cardiac myocytes.
      Furthermore, metformin significantly improved myocardial cell mitochondrial
      respiration and ATP synthesis compared to vehicle. The cardioprotective effects
      of metformin were ablated in mice lacking functional AMPK or eNOS. This study
      demonstrates that metformin significantly improves left ventricular function and
      survival via activation of AMPK and its downstream mediators, eNOS and PGC
      1alpha, in a murine model of heart failure.

PMID- 19096024
TI  - Pravastatin improves function in hibernating myocardium by mobilizing CD133+ and
      cKit+ bone marrow progenitor cells and promoting myocytes to reenter the growth
      phase of the cardiac cell cycle.
AB  - 3-hydroxy-3-methyl glutaryl coenzyme A reductase inhibitors have been reported to
      increase circulating bone marrow progenitor cells and variably improve global
      function in heart failure. The potential role of improved perfusion versus direct
      effects of statins on cardiac myocytes has not been established. We chronically
      instrumented swine with a left anterior descending artery (LAD) stenosis to
      produce chronic hibernating myocardium with regional contractile dysfunction in
      the absence of heart failure. Hemodynamics, function, perfusion, and
      histopathology were assessed in pigs treated for 5 weeks with pravastatin (n=12)
      versus untreated controls (n=10). Regional LAD wall thickening was depressed
      under baseline conditions (LAD 3.7+/-0.3 versus 6.6+/-0.3 in remote regions,
      P<0.01). It remained unchanged in untreated animals but increased from 3.8+/-0.6
      to 5.2+/-0.5 mm after pravastatin (P<0.01). There was no increase in myocardial
      perfusion at rest or during vasodilation. Pravastatin mobilized circulating
      CD133(+)/cKit(+) bone marrow progenitor cells and increased myocardial tissue
      levels (LAD CD133(+) cells from 140+/-33 to 884+/-167 cells/10(6) myocyte nuclei
      and cKit(+) cells from 223+/-49 to 953+/-123 cells/10(6) myocyte nuclei).
      Pravastatin increased myocytes in mitosis (phospho-histone-H3; 9+/-5 to 43+/-7
      nuclei/10(6) myocyte nuclei, P<0.05) and the growth phase of the cell cycle
      (Ki67; 410+/-82 to 1261+/-235 nuclei/10(6) myocyte nuclei, P<0.05) in diseased
      but not normal hearts. As a result, pravastatin increased LAD myocyte nuclear
      density from 830+/-41 to 1027+/-55 nuclei/mm(2) (P<0.05). These data indicate
      that, in the absence of impaired endothelial function and heart failure,
      dysfunctional hibernating myocardium improves after pravastatin. This effect is
      independent of myocardial perfusion and related to mobilization of
      CD133(+)/cKit(+) bone marrow progenitor cells which stimulate myocyte
      proliferation resulting in quantitative increases in myocyte nuclear density.

PMID- 19096025
TI  - IL-10 inhibits inflammation and attenuates left ventricular remodeling after
      myocardial infarction via activation of STAT3 and suppression of HuR.
AB  - Persistent inflammatory response has adverse effects on left ventricular (LV)
      function and remodeling following acute myocardial infarction. We hypothesized
      that suppression of inflammation with interleukin (IL)-10 treatment attenuates LV
      dysfunction and remodeling after acute myocardial infarction. After the induction
      of acute myocardial infarction, mice were treated with either saline or
      recombinant IL-10, and inflammatory response and LV functional and structural
      remodeling changes were evaluated. IL-10 significantly suppressed infiltration of
      inflammatory cells and expression of proinflammatory cytokines in the myocardium.
      These changes were associated with IL-10-mediated inhibition of p38 mitogen
      activated protein kinase activation and repression of the cytokine mRNA
      stabilizing protein HuR. IL-10 treatment significantly improved LV functions,
      reduced infarct size, and attenuated infarct wall thinning. Myocardial infarction
      induced increase in matrix metalloproteinase (MMP)-9 expression and activity was
      associated with increased fibrosis, whereas IL-10 treatment reduced both MMP-9
      activity and fibrosis. Small interfering RNA knockdown of HuR mimicked IL-10
      mediated reduction in MMP-9 expression and activity in NIH3T3 cells. Moreover, IL
      10 treatment significantly increased capillary density in the infarcted
      myocardium which was associated with enhanced STAT3 phosphorylation. Taken
      together, our studies demonstrate that IL-10 suppresses inflammatory response and
      contributes to improved LV function and remodeling by inhibiting fibrosis via
      suppression of HuR/MMP-9 and by enhancing capillary density through activation of
      STAT3.

PMID- 19096026
TI  - Formation of the sinus node head and differentiation of sinus node myocardium are
      independently regulated by Tbx18 and Tbx3.
AB  - The sinus node (or sinoatrial node [SAN]), the pacemaker of the heart, is a
      functionally and structurally heterogeneous tissue, which consists of a large
      "head" within the right caval vein myocardium and a "tail" along the terminal
      crest. Here, we investigated its cellular origin and mechanism of formation.
      Using genetic lineage analysis and explant assays, we identified T-box
      transcription factor Tbx18-expressing mesenchymal progenitors in the inflow tract
      region that differentiate into pacemaker myocardium to form the SAN. We found
      that the head and tail represent separate regulatory domains expressing
      distinctive gene programs. Tbx18 is required to establish the large head
      structure, as seen by the existence of a very small but still functional tail
      piece in Tbx18-deficient fetuses. In contrast, Tbx3-deficient embryos formed a
      morphologically normal SAN, which, however, aberrantly expressed Cx40 and other
      atrial genes, demonstrating that Tbx3 controls differentiation of SAN head and
      tail cardiomyocytes but also demonstrating that Tbx3 is not required for the
      formation of the SAN structure. Our data establish a functional order for Tbx18
      and Tbx3 in SAN formation, in which Tbx18 controls the formation of the SAN head
      from mesenchymal precursors, on which Tbx3 subsequently imposes the pacemaker
      gene program.

PMID- 19096028
TI  - Wnt5a is required for endothelial differentiation of embryonic stem cells and
      vascularization via pathways involving both Wnt/beta-catenin and protein kinase
      Calpha.
AB  - In this study, we examined the signaling pathways activated by Wnt5a in
      endothelial differentiation of embryonic stem (ES) cells and the function of
      Wnt5a during vascular development. We first found that Wnt5a(-/-) mouse embryonic
      stem (mES) cells exhibited a defect in endothelial differentiation, which was
      rescued by addition of Wnt5a, suggesting that Wnt5a is required for endothelial
      differentiation of ES cells. Involvement of both beta-catenin and protein kinase
      (PK)Calpha pathways in endothelial differentiation of mES cells requiring Wnt5a
      was indicated by activation of both beta-catenin and PKCalpha in Wnt5a(+/-) but
      not in Wnt5a(-/-) mES cells. We also found that beta-catenin or PKCalpha
      knockdowns inhibited the Wnt5a-induced endothelial differentiation of ES cells.
      Moreover, the lack of endothelial differentiation of Wnt5a(-/-) mES cells was
      rescued only by transfection of both beta-catenin and PKCalpha, indicating that
      both genes are required for Wnt5a-mediated endothelial differentiation. Wnt5a was
      also found to be essential for the differentiation of mES cells into immature
      endothelial progenitor cells, which are known to play a role in repair of damaged
      endothelium. Furthermore, a defect in the vascularization of the neural tissue
      was detected at embryonic day 14.5 in Wnt5a(-/-) mice, implicating Wnt5a in
      vascular development in vivo. Thus, we conclude that Wnt5a is involved in the
      endothelial differentiation of ES cells via both Wnt/beta-catenin and PKC
      signaling pathways and regulates embryonic vascular development.

PMID- 19096027
TI  - Fate of culture-expanded mesenchymal stem cells in the microvasculature: in vivo
      observations of cell kinetics.
AB  - Vascular delivery of mesenchymal stem cells (MSCs) following myocardial
      infarction is under clinical investigation. Little is known about the
      microvascular fate of MSCs. We used intravital microscopy of rat cremaster muscle
      microcirculation to track intraarterially delivered MSCs. Rat MSCs (average
      diameter, 23 microm) were bolused into the ipsilateral common iliac artery.
      Interrogation of an arteriole-venule pair revealed that 92+/-7% (n=6) of MSCs
      arrest and interrupt flow during first pass at the precapillary level, resulting
      in decreased flow in the feeding arteriole (velocity decreased from 6.3+/-1.0 to
      4.6+/-1.3 mm/sec; P<0.001). MSC deformability evaluated using filtration through
      polycarbonate membranes revealed that the cortical tension of MSCs (0.49+/-0.07
      dyne/cm, n=9) was not different from that of circulating mononuclear cells
      (0.50+/-0.05 dyne/cm, n=7). When intravital microscopy was performed 3 days
      following injection, the number of MSCs in the cremaster further decreased to 14%
      of the initial number, because of cell death in situ. In vivo labeling of the
      basement membrane revealed that at 1 day, the surviving cells were spread out on
      the luminal side of the microvessel, whereas at 3 days, they integrated in the
      microvascular wall. Despite their deformability, intraarterially delivered MSCs
      entrap at the precapillary level because of their large size, with a small
      proportion of surviving MSCs integrating in a perivascular niche.

PMID- 19096029
TI  - Gap junction remodeling and spironolactone-dependent reverse remodeling in the
      hypertrophied heart.
AB  - Pressure overload is a common pathological insult to the heart and the resulting
      hypertrophy is an independent risk factor for sudden cardiac death. Gap junction
      remodeling (GJR) has been described in hypertrophied hearts; however, a detailed
      understanding of the remodeling process and its effects on impulse propagation is
      lacking. Moreover, there has been little progress developing therapeutic
      strategies to diminish GJR. Accordingly, transverse aortic banding (TAC) was
      performed in mice to determine the effects of progressive pathological
      hypertrophy on connexin (Cx)43 expression, posttranslational phosphorylation, gap
      junction assembly, and impulse propagation. Within 2 weeks after TAC, total and
      phospho-Cx43 abundance was reduced and incorporation of Cx43 into gap junctional
      plaques was markedly diminished. These molecular changes were associated with
      progressive slowing of impulse propagation, as determined by optical mapping with
      voltage-sensitive dyes. Treatment with the aldosterone receptor antagonist
      spironolactone, which has been shown to diminish sudden arrhythmic death in
      clinical trials, was examined for its effects on GJR. We found that
      spironolactone blunted the development of GJR and also potently reversed
      established GJR, both at the molecular and functional levels, without diminishing
      the extent of hypertrophy. These data suggest a potential mechanism for some of
      the salutary electrophysiological and clinical effects of mineralocorticoid
      antagonists in myopathic hearts.

PMID- 19096030
TI  - miR-133 and miR-30 regulate connective tissue growth factor: implications for a
      role of microRNAs in myocardial matrix remodeling.
AB  - The myocardium of the failing heart undergoes a number of structural alterations,
      most notably hypertrophy of cardiac myocytes and an increase in extracellular
      matrix proteins, often seen as primary fibrosis. Connective tissue growth factor
      (CTGF) is a key molecule in the process of fibrosis and therefore seems an
      attractive therapeutic target. Regulation of CTGF expression at the promoter
      level has been studied extensively, but it is unknown how CTGF transcripts are
      regulated at the posttranscriptional level. Here we provide several lines of
      evidence to show that CTGF is importantly regulated by 2 major cardiac microRNAs
      (miRNAs), miR-133 and miR-30. First, the expression of both miRNAs was inversely
      related to the amount of CTGF in 2 rodent models of heart disease and in human
      pathological left ventricular hypertrophy. Second, in cultured cardiomyocytes and
      fibroblasts, knockdown of these miRNAs increased CTGF levels. Third,
      overexpression of miR-133 or miR-30c decreased CTGF levels, which was accompanied
      by decreased production of collagens. Fourth, we show that CTGF is a direct
      target of these miRNAs, because they directly interact with the 3' untranslated
      region of CTGF. Taken together, our results indicate that miR-133 and miR-30
      importantly limit the production of CTGF. We also provide evidence that the
      decrease of these 2 miRNAs in pathological left ventricular hypertrophy allows
      CTGF levels to increase, which contributes to collagen synthesis. In conclusion,
      our results show that both miR-133 and miR-30 directly downregulate CTGF, a key
      profibrotic protein, and thereby establish an important role for these miRNAs in
      the control of structural changes in the extracellular matrix of the myocardium.

PMID- 19096031
TI  - Macrophages generate reactive oxygen species in response to minimally oxidized
      low-density lipoprotein: toll-like receptor 4- and spleen tyrosine kinase
      dependent activation of NADPH oxidase 2.
AB  - Oxidative modification of low-density lipoprotein (LDL) plays a causative role in
      the development of atherosclerosis. In this study, we demonstrate that minimally
      oxidized LDL (mmLDL) stimulates intracellular reactive oxygen species (ROS)
      generation in macrophages through NADPH oxidase 2 (gp91phox/Nox2), which, in
      turn, induces production of RANTES and migration of smooth muscle cells.
      Peritoneal macrophages from gp91phox/Nox2(-/-) mice or J774 macrophages in which
      Nox2 was knocked down by small interfering RNA failed to generate ROS in response
      to mmLDL. Because mmLDL-induced cytoskeletal changes were dependent on Toll-like
      receptor (TLR)4, we analyzed ROS generation in peritoneal macrophages from wild
      type, TLR4(-/-), or MyD88(-/-) mice and found that mmLDL-mediated ROS was
      generated in a TLR4-dependent, but MyD88-independent, manner. Furthermore, we
      found that ROS generation required the recruitment and activation of spleen
      tyrosine kinase (Syk) and that mmLDL also induced phospholipase PLCgamma1
      phosphorylation and protein kinase C membrane translocation. Importantly, the
      phospholipase Cgamma1 phosphorylation was reduced in J774 cells expressing Syk
      specific short hairpin RNA. Nox2 modulated mmLDL activation of macrophages by
      regulating the expression of proinflammatory cytokines interleukin-1beta,
      interleukin-6, and RANTES. We showed that purified RANTES was able to stimulate
      migration of mouse aortic smooth muscle cells and addition of neutralizing
      antibody against RANTES abolished the migration of mouse aortic smooth muscle
      cells stimulated by mmLDL-stimulated macrophages. These results suggest that
      mmLDL induces generation of ROS through sequential activation of TLR4, Syk,
      phospholipase Cgamma1, protein kinase C, and gp91phox/Nox2 and thereby stimulates
      expression of proinflammatory cytokines. These data help explain mechanisms by
      which endogenous ligands, such as mmLDL, can induce TLR4-dependent,
      proatherogenic activation of macrophages.

PMID- 19096032
TI  - Heparanase alters arterial structure, mechanics, and repair following
      endovascular stenting in mice.
AB  - Heparan sulfate proteoglycans (HSPGs) are potent regulators of vascular
      remodeling and repair. Heparanase is the major enzyme capable of degrading
      heparan sulfate in mammalian cells. Here we examined the role of heparanase in
      controlling arterial structure, mechanics, and remodeling. In vitro studies
      supported that heparanase expression in endothelial cells serves as a negative
      regulator of endothelial inhibition of vascular smooth muscle cell (vSMC)
      proliferation. Arterial structure and remodeling to injury were also modified by
      heparanase expression. Transgenic mice overexpressing heparanase had increased
      arterial thickness, cellular density, and mechanical compliance. Endovascular
      stenting studies in Zucker rats demonstrated increased heparanase expression in
      the neointima of obese, hyperlipidemic rats in comparison to lean rats. The
      extent of heparanase expression within the neointima strongly correlated with the
      neointimal thickness following injury. To test the effects of heparanase
      overexpression on arterial repair, we developed a novel murine model of stent
      injury using small diameter self-expanding stents. Using this model, we found
      that increased neointimal formation and macrophage recruitment occurs in
      transgenic mice overexpressing heparanase. Taken together, these results support
      a role for heparanase in the regulation of arterial structure, mechanics, and
      repair.

PMID- 19096033
TI  - Cyclooxygenase-2-derived prostaglandin F2alpha mediates endothelium-dependent
      contractions in the aortae of hamsters with increased impact during aging.
AB  - Hypertension and vascular dysfunction result in the increased release of
      endothelium-derived contracting factors (EDCFs), whose identity is poorly
      defined. We tested the hypothesis that endothelial cyclooxygenase (COX)-2 can
      generate EDCFs and identified the possible EDCF candidate. Changes in isometric
      tension of aortae of young and aged hamsters were recorded on myograph. Real-time
      changes in intracellular calcium concentrations ([Ca(2+)](i)) in native aortic
      endothelial cells were measured by imaging. Endothelium-dependent contractions
      were triggered by acetylcholine (ACh) after inhibition of nitric oxide production
      and they were abolished by COX-2 but not COX-1 inhibitors or by thromboxane
      prostanoid receptor antagonists. 2-Aminoethoxydiphenyl borate (cation channel
      blocker) eliminated endothelium-dependent contractions and ACh-stimulated rises
      in endothelial cell [Ca(2+)](i). RT-PCR and Western blotting showed COX-2
      expression mainly in the endothelium. Enzyme immunoassay and high-performance
      liquid chromatography-coupled mass spectrometry showed release of prostaglandin
      (PG)F(2alpha) and prostacyclin (PGI(2)) increased by ACh; only PGF(2alpha) caused
      contraction at relevant concentrations. COX-2 expression, ACh-stimulated
      contractions, and vascular sensitivity to PGF(2alpha) were augmented in aortae
      from aged hamsters. Human renal arteries also showed thromboxane-prostanoid
      receptor-mediated ACh- or PGF(2alpha)-induced contractions and COX-2-dependent
      release of PGF(2alpha). The present study demonstrates that PGF(2alpha), derived
      from COX-2, which is localized primarily in the endothelium, is the most likely
      EDCF underlying endothelium-dependent, thromboxane-prostanoid receptor-mediated
      contractions to ACh in hamster aortae. These contractions involved increases in
      endothelial cell [Ca(2+)](i). The results support a critical role of COX-2 in
      endothelium-dependent contractions in this species with an increased importance
      during aging and, possibly, a similar relevance in humans.

PMID- 19096034
TI  - Regulation of surfactant protein B gene expression in bone marrow-derived cells.
AB  - While investigating the differentiation potential of bone marrow-derived cells,
      we previously demonstrated upregulated expression of the lung-related surfactant
      protein B (SP-B) gene in hematopoietic progenitor cells (HPCs) when they were
      cocultured with macerated lung tissue. During coculture, HPCs differentiated
      toward a dendritic-like myeloid cell phenotype (hematopoietic progenitor cell
      derived dendritic-like cells [HPC-DCs]). However, immature dendritic cells (iDCs)
      cocultured under identical conditions did not express SP-B mRNA before or after
      coculture. We have now further examined the regulation of SP-B expression in HPC
      DCs and iDCs. Of the transcription factors involved in SP-B gene expression,
      neither cell type expressed TTF-1, HNF3alpha, or HNF3beta, but both cell types
      expressed Sp1 and Sp3. Sp1 binding to the SP-B promoter was investigated in these
      cells. Three novel Sp1 binding motifs were identified in the mouse SP-B promoter.
      Using chromatin immunoprecipitation, it was demonstrated that Sp1 was bound to
      all three sites in HPC-DCs after coculture with lung tissue, but not in iDCs. We
      hypothesized that although genes from multiple lineages may be active in HPCs,
      gene silencing events, such as methylation, may subsequently occur to suppress
      expression of these genes in more mature myeloid cells, such as iDCs. Treatment
      with the demethylating agent 5-azacytidine resulted in expression of the SP-B
      gene in iDCs. These data indicate that tissue-specific transcription factors are
      not required to express the lung-related gene SP-B in hematopoietic progenitor
      cells. Furthermore, silencing events, such as methylation, may occur to suppress
      lung-related gene expression as progenitor cells become committed toward more
      mature hematopoietic cell phenotypes.

PMID- 19096035
TI  - Induced pluripotent stem cell generation using a single lentiviral stem cell
      cassette.
AB  - Induced pluripotent stem (iPS) cells can be generated using retroviral vectors
      expressing Oct4, Klf4, Sox2, and cMyc. Most prior studies have required multiple
      retroviral vectors for reprogramming, resulting in high numbers of genomic
      integrations in iPS cells and limiting their use for therapeutic applications.
      Here we describe the use of a single lentiviral vector expressing a "stem cell
      cassette" composed of the four transcription factors and a combination of 2A
      peptide and internal ribosome entry site technology, generating iPS cells from
      postnatal fibroblasts. iPS cells generated in this manner display embryonic stem
      cell-like morphology, express stem cell markers, and exhibit in vivo
      pluripotency, as evidenced by their ability to differentiate in teratoma assays
      and their robust contribution to mouse chimeras. Combining all factors into a
      single transcript achieves the most efficient reprogramming system to date and
      allows derivation of iPS cells with a single viral integration. The use of a
      single lentiviral vector for reprogramming represents a powerful laboratory tool
      and a significant step toward the application of iPS technology for clinical
      purposes.

PMID- 19096037
TI  - Neural progenitors of the postnatal and adult mouse forebrain retain the ability
      to self-replicate, form neurospheres, and undergo multipotent differentiation in
      vivo.
AB  - Somatic stem cells are reservoirs to replace lost cells or damaged tissue. Cells
      with neural stem cell (NSC) characteristics can be isolated from the postnatal
      mammalian brain into adulthood and expanded as neurospheres. We addressed the
      ability of these in vitro expanded putative NSCs to retain progenitor
      characteristics in vivo, in analogy to hematopoietic stem cells. When
      transplanted in utero, both postnatal and adult neural progenitors colonize host
      brains and contribute neurons and glia. In stark contrast to what has been
      reported when transplanted in postnatal hosts, epidermal growth factor-expanded
      cells also remain self-replicating and multipotent in vivo over many months and
      can be serially transplanted into multiple hosts. Surprisingly, embryonically
      transplanted NSCs remain in the neurogenic regions in adult hosts, where they
      express progenitor cell markers and continue to proliferate even after 6 months
      without tumor formation. These data indicate that spherogenic cells of the
      postnatal and adult mammalian brain retain their potential in vitro and in vivo
      throughout the life of the organism and beyond transplantation, which has
      important implications for cell replacement strategies.

PMID- 19096038
TI  - Reciprocal interactions between human mesenchymal stem cells and gammadelta T
      cells or invariant natural killer T cells.
AB  - The immunomodulatory activities of human mesenchymal stem cells (MSCs) provide a
      rational basis for their application in the treatment of immune-mediated
      diseases, such as graft versus host disease and multiple sclerosis. The effects
      of MSCs on invariant natural killer T (iNKT) and gammadelta T cells, both
      involved in the pathogenesis of autoimmune diseases, are unknown. Here, we
      investigated the effects of MSCs on in vitro expansion of these unconventional T
      cell populations. MSCs inhibited iNKT (Valpha24(+)Vbeta11(+)) and gammadelta T
      (Vdelta2(+)) cell expansion from peripheral blood mononuclear cells in both cell
      to-cell contact and transwell systems. Such inhibition was partially counteracted
      by indomethacin, a prostaglandin E(2) inhibitor. Block of indoleamine 2,3
      deoxygenase and transforming growth factor beta1 did not affect
      Valpha24(+)Vbeta11(+) and Vdelta2(+) cell expansion. MSCs inhibited interferon
      gamma production by activated Valpha24(+)Vbeta11(+) and impaired CD3-mediated
      proliferation of activated Valpha24(+)Vbeta11(+) and Vdelta2(+) T cells, without
      affecting their cytotoxic potential. MSCs did not inhibit antigen
      processing/presentation by activated Vdelta2(+) T cells to CD4(+) T cells. In
      contrast, MSCs were lysed by activated Vdelta2(+) T cells through a T-cell
      receptor-dependent mechanism. These results are translationally relevant in view
      of the increasing interest in MSC-based therapy of autoimmune diseases.

PMID- 19096039
TI  - Autocrine regulation of interferon gamma in mesenchymal stem cells plays a role
      in early osteoblastogenesis.
AB  - Interferon (IFN)gamma is a strong inhibitor of osteoclast differentiation and
      activity. However, its role in osteoblastogenesis has not been carefully
      examined. Using microarray expression analysis, we found that several IFNgamma
      inducible genes were upregulated during early phases of osteoblast
      differentiation of human mesenchymal stem cells (hMSCs). We therefore
      hypothesized that IFNgamma may play a role in this process. We first observed a
      strong and transient increase in IFNgamma production following hMSC induction to
      differentiate into osteoblasts. We next blocked this endogenous production using
      a knockdown approach with small interfering RNA and observed a strong inhibition
      of hMSC differentiation into osteoblasts with a concomitant decrease in Runx2, a
      factor indispensable for osteoblast development. Additionally, exogenous addition
      of IFNgamma accelerated hMSC differentiation into osteoblasts in a dose-dependent
      manner and induced higher levels of Runx2 expression during the early phase of
      differentiation. We next examined IFNgamma signaling in vivo in IFNgamma receptor
      1 knockout (IFNgammaR1(-/-)) mice. Compared with their wild-type littermates,
      IFNgammaR1(-/-) mice exhibited a reduction in bone mineral density. As in the in
      vitro experiments, MSCs obtained from IFNgammaR1(-/-) mice showed a lower
      capacity to differentiate into osteoblasts. In summary, we demonstrate that the
      presence of IFNgamma plays an important role during the commitment of MSCs into
      the osteoblastic lineage both in vitro and in vivo, and that this process can be
      accelerated by exogenous addition of IFNgamma. These data therefore support a new
      role for IFNgamma as an autocrine regulator of hMSC differentiation and as a
      potential new target of bone-forming cells in vivo.

PMID- 19096040
TI  - Activation of hedgehog signaling inhibits osteoblast differentiation of human
      mesenchymal stem cells.
AB  - Mesenchymal stem cells within the bone are responsible for the generation of
      osteoblasts, chondrocytes, and adipocytes. In rodents, Indian hedgehog has been
      shown to play a role in osteoblast differentiation. However, evidence for a
      direct function of hedgehog (Hh) in human osteoblastic differentiation is
      missing. Using different models of human mesenchymal stem cells we show that Hh
      signaling decreases during osteoblast differentiation. This is associated with a
      decrease in Smoothened expression, a key partner that triggers Hh signaling, and
      in the number of cells displaying a primary cilium, an organelle necessary for Hh
      signaling. Remarkably, treatment of human mesenchymal stem cells with sonic
      hedgehog or two molecules able to activate Hh signaling inhibits osteoblast
      differentiation. This inhibition is visualized through a decrease in
      mineralization and in the expression of osteoblastic genes. In particular,
      activation of Hh signaling induces a decrease in Runx2 expression, a key
      transcriptional factor controlling the early stage of osteoblast differentiation.
      Consistently, the activation of Hh signaling during the first days of
      differentiation is sufficient to inhibit osteoblast differentiation, whereas
      differentiated osteoblasts are not affected by Hh signaling. In summary, we show
      here, using various inducers of Hh signaling and mesenchymal stem cells of two
      different origins, that Hh signaling inhibits human osteoblast differentiation,
      in sharp contrast to what has been described in rodent cells. This species
      difference should be taken into account for screening for pro-osteogenic
      molecules.

PMID- 19096041
TI  - Tumor immunotherapy using gene-modified human mesenchymal stem cells loaded into
      synthetic extracellular matrix scaffolds.
AB  - Mesenchymal stem cells (MSCs) are appealing as gene therapy cell vehicles given
      their ease of expansion and transduction. However, MSCs exhibit immunomodulatory
      and proangiogenic properties that may pose a risk in their use in anticancer
      therapy. For this reason, we looked for a strategy to confine MSCs to a
      determined location, compatible with a clinical application. Human MSCs
      genetically modified to express luciferase (MSC(luc)), seeded in a synthetic
      extracellular matrix (sECM) scaffold (sentinel scaffold) and injected
      subcutaneously in immunodeficient mice, persisted for more than 40 days, as
      assessed by bioluminescence imaging in vivo. MSCs modified to express a
      bispecific alpha-carcinoembryonic antigen (alphaCEA)/alphaCD3 diabody (MSC(dAb))
      and seeded in an sECM scaffold (therapeutic scaffolds) supported the release of
      functional diabody into the bloodstream at detectable levels for at least 6 weeks
      after implantation. Furthermore, when therapeutic scaffolds were implanted into
      CEA-positive human colon cancer xenograft-bearing mice and human T lymphocytes
      were subsequently transferred, circulating alphaCEA/alphaCD3 diabody activated T
      cells and promoted tumor cell lysis. Reduction of tumor growth in MSC(dAb)
      treated mice was statistically significant compared with animals that only
      received MSC(luc). In summary, we report here for the first time that human MSCs
      genetically engineered to secrete a bispecific diabody, seeded in an sECM
      scaffold and implanted in a location distant from the primary tumor, induce an
      effective antitumor response and tumor regression.

PMID- 19096042
TI  - Lineage-negative bone marrow cells protect against chronic renal failure.
AB  - Progressive renal failure continues to be a challenge. The use of bone marrow
      cells represents a means of meeting that challenge. We used lineage-negative
      (Lin(-)) cells to test the hypothesis that Lin(-) cell treatment decreases renal
      injury. Syngeneic Fischer 344 rats were divided into four groups: sham
      (laparotomy only, untreated); Nx (five-sixth nephrectomy and untreated); NxLC1
      (five-sixth nephrectomy and receiving 2 x 10(6) Lin(-) cells on postnephrectomy
      day 15); and NxLC3 (five-sixth nephrectomy and receiving 2 x 10(6) Lin(-) cells
      on postnephrectomy days 15, 30, and 45). On postoperative day 16, renal mRNA
      expression of interleukin (IL)-1beta, tumor necrosis factor-alpha, and IL-6 was
      lower in NxLC rats than in Nx rats. On postnephrectomy day 60, NxLC rats
      presented less proteinuria, glomerulosclerosis, anemia, renal infiltration of
      immune cells, and protein expression of monocyte chemoattractant protein-1, as
      well as decreased interstitial area. Immunostaining for proliferating cell
      nuclear antigen showed that, in comparison with sham rats, Nx rats presented
      greater cell proliferation, whereas NxLC1 rats and NxLC3 rats presented less cell
      proliferation than did Nx rats. Protein expression of the cyclin-dependent kinase
      inhibitor p21 and of vascular endothelial growth factor increased after
      nephrectomy and decreased after Lin(-) cell treatment. On postnephrectomy day
      120, renal function (inulin clearance) was significantly better in Lin(-) cell
      treated rats than in untreated rats. Lin(-) cell treatment significantly improved
      survival. These data suggest that Lin(-) cell treatment protects against chronic
      renal failure.

PMID- 19096043
TI  - Identification of a small subpopulation of candidate leukemia-initiating cells in
      the side population of patients with acute myeloid leukemia.
AB  - In acute myeloid leukemia (AML), apart from the CD34(+)CD38(-) compartment, the
      side population (SP) compartment contains leukemic stem cells (LSCs). We have
      previously shown that CD34(+)CD38(-) LSCs can be identified using stem cell
      associated cell surface markers, including C-type lectin-like molecule-1 (CLL-1),
      and lineage markers, such as CD7, CD19, and CD56. A similar study was performed
      for AML SP to further characterize the SP cells with the aim of narrowing down
      the putatively very low stem cell fraction. Fluorescence-activated cell sorting
      (FACS) analysis of 48 bone marrow and peripheral blood samples at diagnosis
      showed SP cells in 41 of 48 cases that were partly or completely positive for the
      markers, including CD123. SP cells in normal bone marrow (NBM) were completely
      negative for markers, except CD123. Further analysis revealed that the SP
      fraction contains different subpopulations: (a) three small lymphoid
      subpopulations (with T-, B-, or natural killer-cell markers); (b) a
      differentiated myeloid population with high forward scatter (FSC(high)) and high
      sideward scatter (SSC(high)), high CD38 expression, and usually with aberrant
      marker expression; (c) a more primitive FSC(low)/SSC(low), CD38(low), marker
      negative myeloid fraction; and (d) a more primitive FSC(low)/SSC(low), CD38(low),
      marker-positive myeloid fraction. NBM contained the first three populations,
      although the aberrant markers were absent in the second population. Suspension
      culture assay showed that FSC(low)/SSC(low) SP cells were highly enriched for
      primitive cells. Fluorescence in situ hybridization (FISH) analyses showed that
      cytogenetically abnormal colonies originated from sorted marker positive cells,
      whereas the cytogenetically normal colonies originated from sorted marker
      negative cells. In conclusion, AML SP cells could be discriminated from normal SP
      cells at diagnosis on the basis of expression of CLL-1 and lineage markers. This
      reveals the presence of a low-frequency (median, 0.0016%) SP subfraction as a
      likely candidate to be enriched for leukemia stem cells.

PMID- 19096044
TI  - Identification of glucose-regulated miRNAs from pancreatic {beta} cells reveals a
      role for miR-30d in insulin transcription.
AB  - MicroRNAs (miRNAs) are small noncoding ribonucleotides that bind mRNAs and
      function mainly as translational repressors in mammals. MicroRNAs have been
      implicated to play a role in many diseases, including diabetes. Several reports
      indicate an important function for miRNAs in insulin production as well as
      insulin secretion. We have recently carried out a screen in the pancreatic beta
      cell line MIN6 to identify miRNAs with altered abundance in response to changes
      in glucose concentrations. This screen resulted in identification of 61 glucose
      regulated miRNAs from a total of 108 miRNAs detectable in MIN6 cells. Many of the
      identified miRNAs, including miR-124a, miR-107, and miR-30d were up-regulated in
      the presence of high glucose. Only a few of the miRNAs, including miR-296, miR
      484, and miR-690 were significantly down-regulated by high glucose treatment.
      Interestingly, we found that overexpression of miR-30d, one of the miRNAs up
      regulated by glucose, increased insulin gene expression, while inhibition of miR
      30d abolished glucose-stimulated insulin gene transcription. Overexpression or
      inhibition of miR-30d did not have any effect on insulin secretion. These data
      suggest that the putative target genes of miR-30d may be negative regulators of
      insulin gene expression.

PMID- 19096045
TI  - The MRB1 complex functions in kinetoplastid RNA processing.
AB  - Mitochondrial (mt) gene expression in Trypanosoma brucei entails multiple types
      of RNA processing, including polycistronic transcript cleavage, mRNA editing,
      gRNA oligouridylation, and mRNA polyadenylation, which are catalyzed by various
      multiprotein complexes. We examined the novel mitochondrial RNA-binding 1 (MRB1)
      complex that has 16 associated proteins, four of which have motifs suggesting RNA
      interaction. RNase treatment or the lack of kDNA in mutants resulted in lower
      MRB1 complex sedimentation in gradients, indicating that MRB1 complex associates
      with kDNA transcripts. RNAi knockdowns of expression of the Tb10.406.0050
      (TbRGGm, RGG motif), Tb927.6.1680 (C2H2 zinc finger), and Tb11.02.5390 (no known
      motif) MRB1 proteins each inhibited in vitro growth of procyclic form parasites
      and resulted in cells with abnormal numbers of nuclei. Knockdown of TbRGGm, but
      not the other two proteins, disrupted the MRB1 complex, indicating that it, but
      perhaps not the other two, is required for complex assembly and/or stability. The
      knockdowns resulted in similar but nonidentical patterns of altered in vivo
      abundances of edited, pre-edited, and preprocessed mt mRNAs, but did not
      appreciably affect the abundances of mRNAs that do not get edited. These results
      indicate that MRB1 complex is critical to the processing of mt RNAs, and although
      its specific function is unknown, it appears essential to parasite viability.

PMID- 19096046
TI  - Molecular and cellular mechanisms of the thrombotic complications of
      atherosclerosis.
AB  - Clinicians have traditionally regarded the complications of atherosclerosis as a
      consequence of progressive arterial stenosis leading to critical narrowings that
      impede blood flow. Our contemporary understanding of the thrombotic complications
      of atherosclerosis has undergone a transformation based on a body of observations
      by pathologists and clinicians. In the late 1980s, clinicians had to confront the
      counterintuitive notion that plaques that cause acute myocardial infarction often
      do not produce high-grade stenoses (Smith, S. C., Jr. 1996. Risk-reduction
      therapy: the challenge to change. Circulation. 93: 2205-2211.). Observations from
      serial angiographic studies and on culprit lesions of acute myocardial infarction
      postthrombolysis highlighted this apparent paradox. These contrarian clinical
      findings prompted cardiologists to consider more carefully the findings of
      generations of pathologists that plaques that cause fatal coronary thrombi often
      result from a physical disruption of the atheromatous plaque that may not indeed
      cause critical arterial narrowing. This convergence of clinical and pathological
      observations highlighted the importance of understanding the mechanisms of
      disruption of plaques that can precipitate thromboses.

PMID- 19096047
TI  - Identification of phosphatidylserylglutamate: a novel minor lipid in Escherichia
      coli.
AB  - Advances in mass spectrometry have facilitated the identification of novel lipid
      structures. In this work, we fractionated the lipids of Escherichia coli B and
      analyzed the fractions using negative-ion electrospray ionization mass
      spectrometry to reveal unknown lipid structures. Analysis of a fraction eluting
      with high salt from DEAE cellulose revealed a series of ions not corresponding to
      any of the known lipids of E. coli. The ions, with m/z 861.5, 875.5, 887.5,
      889.5, and 915.5, were analyzed using collision-induced dissociation mass
      spectrometry (MS/MS) and yielded related fragmentation patterns consistent with a
      novel diacylated glycerophospholipid. Product ions arising by neutral loss of 216
      mass units were observed with all of the unknowns. A corresponding negative
      product ion was also observed at m/z 215.0. Additional ions at m/z 197.0, 171.0,
      146.0, and 128.0 were used to propose the novel structure
      phosphatidylserylglutamate (PSE). The hypothesized structure was confirmed by
      comparison with the MS/MS spectrum of a synthetic standard. Normal phase liquid
      chromatography-mass spectrometry analysis further showed that the endogenous PSE
      and synthetic PSE eluted with the same retention times. PSE was also observed in
      the equivalent anion exchange fractions of total lipids extracted from the wild
      type E. coli K-12 strain MG1655.

PMID- 19096049
TI  - Importance of peer-reviewed science in the debates on public policy.

PMID- 19096050
TI  - An examination of anatomic, physiologic, and metabolic factors associated with
      well-being of broilers differing in field gait score.
AB  - An experiment was conducted to evaluate potential differences for indicators of
      well-being in birds classified as having field gait score (FGS)2 and 3 and to
      evaluate potential causal factors affecting gait score. In 2 trials, birds with
      FGS2 and FGS3 were similar for most broiler traits (BW, feed conversion ratio)
      and fearfulness. Birds with FGS3, however, had improved breast conformation score
      in both studies and greater breast angle in the second trial compared with birds
      with FGS2. This improved breast conformation, along with differing ratios of
      length (hip to neck/hip to tail; P < 0.05), appears to be highly related to gait
      score. In other words, varying a bird's physical proportions necessitates that
      the bird's gait changes to maintain center of gravity during locomotion. In trial
      2, behaviors were measured to determine if gait score affected behavior. Birds
      with FGS3 rested more and stood less than those with FGS2. Similar pathological
      analysis and heterophil:lymphocyte ratio suggest that gait score differences are
      not due to increased physiological stress or stress-associated pain. The lack of
      difference in heterophil:lymphocyte ratio, respiratory quotient, and pathology,
      combined with differing ratios of body proportions and anatomical length ratios,
      suggests that behavior and gait differences between birds with differing FGS
      occur with similar levels of well-being.

PMID- 19096048
TI  - A shotgun lipidomics approach in Sinorhizobium meliloti as a tool in functional
      genomics.
AB  - A shotgun lipidomics approach that allowed the analysis of eight lipid classes
      directly from crude extracts of the soil bacterium Sinorhizobium meliloti is
      presented. New MS-MS transitions are reported for the analysis of
      monomethylphosphatidylethanolamines, dimethylphosphatidylethanolamines, and three
      bacterial non-phosphorus-containing lipid classes
      [sulfoquinovosyldiacylglycerols, ornithines, and diacylglyceryl-(N,N,N-trimethyl)
      homoserines]. Unique MS-MS transitions allowed the analysis of isomeric species
      from various lipid classes without chromatography. Analyses required small sample
      amounts and minimal preparation; thus, this methodology has excellent potential
      to be used as a screening tool for the analysis of large numbers of samples in
      functional genomics studies. FA distributions within lipid classes of S. meliloti
      are described for the first time, and the relative positions of fatty acyl
      substituents (sn-1, sn-2) in phospholipids are presented. FA distributions in
      diacylglyceryl-(N,N,N-trimethyl)-homoserines were identical to those of
      phospholipids, indicating a common biosynthetic origin for these lipids. The
      method was applied to the analysis of mutants deficient in the PhoB regulator
      protein. Increased lipid cyclopropanation was observed in PhoB-deficient mutants
      under P(i) starvation.

PMID- 19096051
TI  - Remote monitoring of electroencephalogram, electrocardiogram, and behavior during
      controlled atmosphere stunning in broilers: implications for welfare.
AB  - This study examined the welfare implications of euthanizing broilers with 3 gas
      mixtures relevant to the commercial application of controlled atmosphere stunning
      (CAS). Birds were implanted/equipped with electrodes to measure brain activity
      (electroencephalogram, EEG) and heart rate. These signals were recorded using a
      purpose-built telemetry-logging system, small enough to be worn by each bird in a
      spandex backpack. The birds were euthanized in a scaled-down CAS apparatus
      consisting of a conveyor belt passing through 2 compartments. Three gas
      environments were applied (8 birds per treatment): 1) anoxia (N(2) with <2%
      residual O(2), in both compartments), 2) hypercapnic anoxia (N(2) with 30% CO(2)
      and <2% residual O(2), in both compartments), and 3) a 2-phase approach with a
      hypercapnic hyperoxygenated anesthetic phase (40% CO(2), 30% O(2), and 30% N(2),
      in the first compartment, 80 s) followed by a second euthanasia phase (80% CO(2)
      in air, in the second compartment). All 3 CAS approaches effectively achieved
      nonrecovery states, and time to loss of consciousness for each bird was
      determined by visual determination of isoelectric EEG and by calculation of the
      correlation dimension of the EEG. Hypercapnic anoxia resulted in rapid
      unconsciousness and death; both anoxic treatments were associated with early
      onset prolonged wing flapping and sustained tonic convulsions as displayed in the
      electrophysiological recordings. These responses were seen in the period when
      consciousness remained a possibility. Hypercapnic hyperoxygenation (the 2-phase
      approach) was associated with respiratory disruption, but this treatment
      eliminated initial clonic convulsions in the stunning process, and tonic
      convulsions were not seen. These results suggest that the presence of O(2) in the
      first stage of CAS is associated with an absence of potentially distressing
      behavioral responses. The respiratory discomfort associated with hypercapnic
      hyperoxygenation is an issue. We propose that this may be compensated by a more
      gradual induction to unconsciousness, which eliminates the impact of other
      potentially negative experiences.

PMID- 19096052
TI  - The effect of light intensity on the behavior, eye and leg health, and immune
      function of broiler chickens.
AB  - Broilers are typically raised commercially in dim lighting. It has been suggested
      that providing brighter light intensity could improve health and provide
      opportunities for more normal behavioral rhythms. We examined the effects of 3
      photophase light intensities (5, 50, and 200 lx) on activity patterns, immune
      function, and eye and leg condition of broilers (n = 753; 6 replicate
      pens/treatment). Broilers were reared with one of these intensities from 1 to 6
      wk of age; photoperiod consisted of 16L:8D with 1 lx intensity during the
      scotophase. Broilers reared with 5 lx were less active (P = 0.023) during the day
      than 50 or 200 lx and showed less (P < 0.0001) change in activity between day and
      night than 50 or 200 lx. There was no difference between treatments for final BW
      (2.30 +/- 0.02 kg) or for most immune parameters (IgG primary and secondary
      responses to keyhole limpet hemocyanin, B and T lymphocyte proliferation, plasma
      lysozyme, haptoglobin, NO, whole blood killing of Escherichia coli and
      Staphylococcus aureus), but there was a trend (P = 0.072) for a greater IgM
      response in 50 lx (6.21 titer) than 5 lx (5.78 titer), with 200 lx (5.92 titer)
      intermediate. There was no effect of light intensity on back-to-front (1.13 +/-
      0.01 cm) or side-to-side (1.48 +/- 0.01 cm) diameter of the eyes or on corneal
      radii (0.82 +/- 0.01 cm), but 5 lx (2.33 +/- 0.07 g) had heavier eyes (P = 0.002)
      than 50 lx (2.09 +/- 0.04 g) or 200 lx (2.11 +/- 0.04 g). There were no
      differences in gait score, although 200 lx broilers had more hock and footpad
      bruising (P = 0.038) but fewer erosions (P = 0.006) than 5 or 50 lx. Increased
      daylight intensity had little effect on broiler health but resulted in more
      pronounced behavioral rhythms.

PMID- 19096053
TI  - Effect of providing light during incubation on the health, productivity, and
      behavior of broiler chickens.
AB  - Environmental stimuli present during incubation can affect the behavior and
      health of birds posthatch. Commercial broiler chickens are often incubated in
      complete darkness, receiving light only intermittently when the incubator is
      opened. To determine the effect of providing light during the prehatch period, we
      incubated Cobb broiler eggs (n = 664) under continuous light (24L:0D), no light
      (0L:24D), or 12 h of light (12L:12D); the light level was 550 lx. Various
      parameters were measured posthatch in these broilers (n = 506), which were raised
      in floor pens on a 12L:12D regimen. There were no incubation treatment
      differences in hatchability, mortality, growth, feed consumption, feed conversion
      ratio, gait score, overall feeding behavior activity, or general behavioral
      activity. However, broilers hatched from eggs incubated under 24L:0D or 12L:12D
      had greater feeding activity (P < 0.05) than the 0L:24D broilers during the 2 h
      after the lights came on. Eye dimensions did not differ between treatments, but
      the eyes of the 12L:12D broilers weighed less (P < 0.05) than those of the other
      treatments. Broilers incubated under 0L:24D had a greater level of composite
      physical asymmetry (1.87 +/- 0.11 mm), considered to be an indicator of
      developmental stress, than did 12L:12D (1.57 +/- 0.09 mm; P = 0.05) broilers;
      they also tended to have more composite asymmetry than 24L:0D (1.62 +/- 0.11 mm;
      P = 0.10) broilers. The results of this study indicate that providing light
      during incubation has no detrimental effect on production or health of broilers,
      but does have potential benefits in terms of reducing the effects of stressors
      associated with production and growth.

PMID- 19096054
TI  - Infrared beak treatment method compared with conventional hot-blade trimming in
      laying hens.
AB  - Infrared lasers have been widely used for noninvasive surgical applications in
      human medicine, and their results are reliable, predictable, and reproducible.
      Infrared lasers have recently been designed for the express purpose of providing
      a less painful, more precise beak-trimming method compared with conventional beak
      trimming. This study was designed to examine the potential of the infrared (IR)
      beak treatment to provide a welfare-friendly alternative to the conventional hot
      blade method for chickens. The birds were beak trimmed by IR at the hatchery or
      by hot blade at 7 to 10 d of age in a commercial production setting, in
      accordance with standard procedures. The beak morphology and associated
      physiological characteristics, including production and aggressive behavior of
      the birds, were analyzed at 30 wk of age. There was no difference in egg
      production or bird BW between the 2 beak-trimming treatments. Birds also
      exhibited no difference in stress physiology measured in the study, such as
      fluctuating asymmetry and heterophil and lymphocyte profiles. However, birds
      receiving the IR treatment showed a superior feather condition and reduced
      aggressiveness under high light intensity, even though they had longer beak
      stumps. The results may indicate that the IR beak treatment may reduce the damage
      done by aggressive pecking and feather pecking. Indeed, IR trimming may provide a
      more welfare-friendly alternative to conventional beak trimming without
      compromising productivity.

PMID- 19096055
TI  - Transmission of Salmonella to broilers by contaminated larval and adult lesser
      mealworms, Alphitobius diaperinus (Coleoptera: Tenebrionidae).
AB  - The ability of the lesser mealworm, Alphitobius diaperinus (Panzer), commonly
      known as the darkling beetle, to transmit marker Salmonella Typhimurium to day-of
      hatch broiler chicks was evaluated, as well as the spread to nonchallenged pen
      mates. In trial 1, day-of-hatch chicks were orally gavaged with 4 larval or 4
      adult beetles that had been exposed to marker Salmonella-inoculated feed for 72
      h. In addition, chicks were gavaged with the marker Salmonella in saline
      solution. These chicks were then placed into pens to serve as challenged
      broilers. In trial 2, all pens received 2 challenged chicks that were gavaged
      with larvae or beetles that had been exposed to marker Salmonella-inoculated feed
      for 24 h and then removed from the inoculated feed for a period of 7 d. At 3 wk
      of age, cecal samples from the marker Salmonella-challenged broilers and from 5
      pen mates in trial 1, or 10 pen mates in trial 2, were evaluated for the presence
      of the marker Salmonella in their ceca, and at 6 wk of age, all remaining pen
      mates were sampled. To monitor the presence of the marker Salmonella within pens,
      stepped-on drag swab litter samples were taken weekly. For the Salmonella-saline
      pens, 29 to 33% of the broilers that had been challenged and 10 to 55% of the pen
      mates were positive at 3 wk of age, and only 2 to 6% had positive ceca at 6 wk.
      For the pens challenged with adult beetles, 0 to 57% of the challenged broilers
      and 20 to 40% of the pen mates had positive ceca at 3 wk, and 4 to 7% were
      positive at 6 wk. The pens challenged with larvae had the greatest percentage of
      marker Salmonella-positive broilers; 25 to 33% of the challenged broilers and 45
      to 58% of pen mates were positive at 3 wk, and 11 to 27% were positive at 6 wk.
      These results demonstrated that ingestion of larval or adult beetles contaminated
      with a marker Salmonella could be a significant vector for transmission to
      broilers.

PMID- 19096056
TI  - Effects of dietary inclusion of probiotic and synbiotic on growth performance,
      organ weights, and intestinal histomorphology of broiler chickens.
AB  - A feeding trial was conducted to investigate the effects of dietary
      supplementations of synbiotic and probiotic on broiler performance, carcass
      yield, organs weights, and histomorphological measurements of small intestine.
      Six hundred 1-d-old broiler chicks were randomly assigned to 1 of 3 dietary
      treatments for 5 wk. The dietary treatments were 1) control, 2) basal diets
      supplemented with synbiotic (1 kg of Biomin IMBO/ ton of the starter diets and
      0.5 kg/ton of the grower diets), 3) basal diets supplemented with probiotic (1 kg
      of a homofermentative and a heterofermentative Lacto-bacillus sp./ton of feed).
      The BW, average daily weight gain, carcass yield percentage, and feed conversion
      rate were significantly (P < 0.05) increased by the dietary inclusion of the
      synbiotic compared with the control and probiotic-fed broilers. Moreover, a
      slight improvement in performance traits was observed in broilers fed the
      probiotic compared with control birds. The absolute and relative weight of spleen
      and thymus tended to be greater (P < 0.1) for the probiotic-supplemented group
      compared with the synbiotic-supplemented group. The relative liver weight was
      greater (P < 0.05) for probiotic-fed birds compared with synbiotic-fed birds.
      Additionally, the weight of small intestine was greater for either probiotic-
      (3.17) or synbiotic-fed birds (3.11) than the controls (2.89). Furthermore,
      dietary treatments influenced the histomorphological measurements of small
      intestinal villi. The addition of either probiotic or synbiotic increased (P <
      0.05) the villus height:crypt depth ratio and villus height in both duodenum and
      ileum. The duodenal crypt depth remained unaffected (P > 0.05). However, the
      ileal crypt depth was decreased by dietary supplementations compared with
      control. In conclusion, synbiotic or probiotic displayed a greater efficacy as
      growth promoters for broilers. Furthermore, the dietary supplementations resulted
      in an increase in the villus height and crypt depth of intestinal mucosa of
      broilers. The increase in the villus height and villus height:crypt depth ratio
      was associated with improvement of growth performance for both synbiotic and
      probiotic. This indicates that the synbiotic and probiotic can be used as a
      growth promoter in broiler diets and can improve the gut health. These products
      show promising effects as alternatives for antibiotics as pressure to eliminate
      growth-promotant antibiotic use increases.

PMID- 19096057
TI  - Comparison of beak-trimming methods on early broiler breeder performance.
AB  - Beak trimming is necessary in commercial broiler breeders to prevent or decrease
      trauma as they mature. Two common beak-trimming methods were evaluated by early
      performance comparison with nontrimmed chicks (NBT). The robotic electrocautery
      device (ECD) trims and cauterizes the beak tip. The robotic infrared beak
      trimming device (IBT) applies an infrared light beam to destroy the live basal
      tissue while leaving the hard corneum intact for the first approximately 10 d. In
      2 experiments, day-of-hatch Ross 708 by-product chicks were obtained from a local
      hatchery, where 1/3 of the chicks were trimmed using IBT. All chicks were then
      transported to another hatchery where 1/3 were trimmed using ECD and 1/3 were
      NBT. Personnel at each hatchery were highly experienced and skilled with their
      respective technique. All chicks were then transported to University of Arkansas
      facilities. Before placement in each experiment, chicks were individually neck
      tagged and weighed, and in experiment 1, beaks were measured using a digital
      caliper. A small but significant transient reduction in BW gain was observed at
      14 d due to ECD as compared with NBT controls, although ECD was not different
      than IBT in experiment 1. In experiment 2, IBT birds were significantly heavier
      at 11 d by 7.8 and 8.7 g than the NBT or ECD, respectively. However, at d 21 and
      42, no significant differences in BW or BW gain were observed. When beak trimming
      was performed on day of hatch by skilled and experienced personnel, little
      measurable effect on early performance was observed during the first 6 wk of
      life. Decreased broiler performance is generally considered a sensitive
      indication of physical or psychogenic stress. Given the marked reduction in beak
      inflicted trauma with beak trimming birds as they reach sexual maturity, these
      results suggest that when properly performed, neither of these beak-trimming
      methods causes sufficient physical or psychogenic stress to markedly affect early
      growth rate.

PMID- 19096058
TI  - The natural feed additive caprylic acid decreases Campylobacter jejuni
      colonization in market-aged broiler chickens.
AB  - Campylobacter causes human foodborne illness, and epidemiological evidence
      indicates poultry and poultry products as a significant source of human
      infection. Decreasing Campylobacter in the poultry intestinal tract would
      decrease contamination of poultry products. Caprylic acid is a medium-chain fatty
      acid reported to be effective in killing a variety of bacterial pathogens,
      including Campylobacter jejuni, but its effect has not been investigated in the
      control of C. jejuni in preslaughter market-aged poultry already colonized with
      this bacterium. The objective of this study was to determine the therapeutic
      effect of caprylic acid on C. jejuni counts in the cecal contents of 42-d-old
      chickens. Four trials were conducted. In the first 2 trials, day-of-hatch chicks
      (n = 60 per trial) were assigned to 6 treatment groups (n = 10 birds per
      treatment group): positive controls (Campylobacter, no caprylic acid), 0.7 or
      1.4% of caprylic acid in feed for the last 3 d of the trial with or without a 12
      h feed withdrawal. Treatments were similar for trials 3 and 4 except the doses
      used were 0.35 or 0.7% caprylic acid supplementation for the last 7 d of the
      trial. On d 42, ceca were collected and Campylobacter counts determined. The
      supplementation of caprylic acid at 0.35 and 0.7% consistently decreased (P <
      0.05) the colonization of C. jejuni in the chicken ceca compared with positive
      control treatment. When these treatments were evaluated after a 12-h feed
      withdrawal period, 0.7% caprylic acid decreased Campylobacter colonization in the
      3-d treatment supplementation. Body weight and feed consumption did not differ
      between the caprylic acid and control groups. The results suggest that
      therapeutic supplementation of caprylic acid in the feed can effectively decrease
      Campylobacter in market-aged chickens and may be a potential treatment for
      decreasing pathogen carriage in poultry.

PMID- 19096059
TI  - Associations among fluctuating asymmetry, duration of tonic immobility,
      heterophil-to-lymphocyte ratio, and one-legged standing, crooked toes, or footpad
      dermatitis in chickens.
AB  - The purpose of this study was to analyze the associations among fluctuating
      asymmetry, duration of tonic immobility, heterophil-to-lymphocyte ratio, and one
      legged standing, crooked toes, or footpad dermatitis in chickens. In experiment
      1, cocks (n = 96; 36 wk old) from 11 Spanish breeds and a White Leghorn
      population that showed one-legged or normal standing were used. There were no
      significant differences for the relative fluctuating asymmetry, the duration of
      tonic immobility, and the heterophil-to-lymphocyte ratio between both groups of
      cocks, with mean values of one-legged standing birds being similar to those of
      normal birds. Thus, this pain-related behavior is not associated with some
      measures of well-being, fear, and stress. In experiment 2, cocks (n = 106; 36 wk
      old) from 9 Spanish breeds and the White Leghorn population that showed crooked
      or normal toes were used. Group effect was not significant for the relative
      fluctuating asymmetry and duration of tonic immobility. Heterophil-to-lymphocyte
      ratio and heterophil number were significantly greater (P < 0.001) in cocks with
      crooked toes and smaller in cocks with normal toes, with the opposite being true
      for lymphocyte number. Thus, this leg problem is associated with the
      stressfulness of birds and does not contribute to their well-being or fear
      levels. In experiment 3, cocks (n = 68; 36 wk old) from 5 Spanish breeds with or
      without footpad dermatitis were used. Group effect was significant for the
      relative asymmetry of toe length (P < 0.05), the relative asymmetry of cocks with
      footpad dermatitis being larger. Group x breed interaction was significant for
      the relative asymmetry of wattle length (P < 0.001), with the difference between
      cocks with footpad dermatitis and normal cocks being significant in one breed. In
      this breed (Red-Barred Vasca), fluctuating asymmetry of wattle length was
      significantly greater in cocks with footpad dermatitis, suggesting that this leg
      problem negatively affects the well-being of cocks.

PMID- 19096060
TI  - Broiler pulmonary hypertensive responses during lipopolysaccharide-induced
      tolerance and cyclooxygenase inhibition.
AB  - Bacterial lipopolysaccharide (LPS, endotoxin) triggers pulmonary hypertension
      (PH) characterized by an increase in pulmonary arterial pressure (PAP) that
      reaches a peak value within 20 to 25 min and then gradually subsides within 60
      min. As the PAP subsides PH cannot be reinitiated, signifying the onset of a
      period of tolerance (refractoriness) to repeated LPS exposure. The present study
      was conducted to determine the duration of this tolerance, and to evaluate key
      mediators thought to contribute to LPS-mediated PH in broilers. Tolerance was
      shown to persist for 4 to 5 d after the initial exposure to LPS. In tolerant
      broilers supramaximal i.v. injections of LPS did not reinitiate PH, nor was a
      significant modulatory role for nitric oxide demonstrated. The pulmonary
      vasculature of tolerant broilers remains responsive to the thromboxane A(2)
      (TxA(2)) mimetic U44069, 5-hydroxytryptamine (5-HT, serotonin), and constitutive
      nitric oxide. Meclofenamate successfully blocked the conversion of arachidonic
      acid to vasoconstrictive eicosanoids such as TxA(2); nevertheless, meclofenamate
      failed to inhibit PH in response to LPS. Therefore, TxA(2) does not appear to be
      the primary vasoconstrictor involved in the PH response to LPS and neither does 5
      HT. Broilers emerging from tolerance 5 d after the initial exposure to LPS
      exhibited interindividual variation in their PH responsiveness to a second LPS
      injection, ranging from zero response (individuals that remain fully tolerant) to
      large increases in PAP (post-tolerant individuals). Tolerance might be an
      important compensatory or protective mechanism for broilers whose pulmonary
      vascular capacity is marginally adequate under optimal conditions, and whose
      respiratory systems are chronically challenged with LPS in commercial production
      facilities. The key vasoconstrictors responsible for the PH elicited by LPS
      remain to be determined.

PMID- 19096061
TI  - Effects of salinomycin on cell-mediated immunity of broiler chickens against
      hydropericardium syndrome and Newcastle disease viruses.
AB  - The effects of salinomycin (SAL) on protective cell-mediated immune (CMI)
      responses of vaccinated and challenged broiler chicks against hydropericardium
      syndrome virus (HPSV) and Newcastle disease (NDV) were investigated while
      comparing 3 reference drugs [levamisole, cyclophosphamide (CYP), and cyclosporine
      (CYS)]. Peripheral lymphoproliferation, skin hypersensitivity reactions, and the
      ability of chicks to resist virulent HPSV and virulent NDV challenges were used
      to determine the effects of drugs on CMI responses in chicks. Salinomycin
      medicated chicks showed significant (P < 0.05) stimulation of lymphoproliferation
      and nonsignificant (P > 0.05) stimulation of skin hypersensitivity reactions
      compared with untreated control chicks. However, skin thickness and
      lymphoproliferation of SAL-medicated chicks were significantly greater (P < 0.05)
      than those of CYP- and CYS-treated chicks. The greatest survival rate was
      recorded in SAL-medicated chicks compared with immune-suppressed (CYP- and CYS
      treated) and untreated control chicks after virulent NDV and virulent HPSV
      challenges. Thus, it was concluded that SAL had beneficial effects on the CMI
      responses of broiler chicks against HPSV and NDV.

PMID- 19096062
TI  - Prediction of true metabolizable energy from chemical composition of wheat
      milling by-products for ducks.
AB  - The present study was conducted to evaluate the effect of chemical composition of
      wheat by-products on the TME value to ducks and to establish the prediction
      models estimating TME. Seven representative samples were selected from 23 wheat
      by-products millings samples based on the neutral detergent fiber (NDF) content.
      According to the Sibbald method, male Cherry Valley ducks were chosen to assay
      the TME of 7 representative samples. Stepwise regression analysis was performed
      to establish the prediction equations of TME using CP, ether extract (EE), NDF,
      acid detergent fiber, crude fiber, and gross energy (GE) as independent
      variables. The NDF, CP, and DM of 23 samples of wheat by-product averaged to be
      33.39 +/- 11.04%, 19.2 +/- 3.25%, 87.17 +/- 0.95%, respectively. The TME values
      of 7 representative samples averaged 12.02 MJ/kg, with much larger CV than GE
      (17.72 vs. 2.82%). The crude fiber, NDF, acid detergent fiber were highly but
      negatively correlated with TME (P < 0.01), in which the greatest correlation
      coefficient (r = -0.969) was observed between NDF and TME. No significant
      correlation of CP, EE, ash, and GE to TME was found among the 7 representative
      samples. The optimal equation in terms of R(2) from using a single chemical
      analysis was obtained in the total group: TME = -0.1564NDF + 17.4696 (R(2) =
      0.94, P = 0.0003), and the TME prediction equation was improved by the addition
      of the EE and CP content to sequential analysis: TME = -0.17NDF + 0.98EE - 0.27CP
      + 19.31 (R(2) = 0.99, residual SD = 0.35, P < 0.01). The results of present study
      suggest that NDF could be used as an effective indicator for the prediction of
      the TME value of wheat by-products for ducks.

PMID- 19096063
TI  - The partitioning of metabolizable energy by broiler chickens.
AB  - Broiler chickens were used to alter the partitioning of ME between maintenance
      and production. They were fed amounts of feed that ranged between ad libitum and
      75 to 80% ad libitum each day from a BW of 1.1 to 2.2 kg. The experiment was done
      with 2 strains of broilers, both sexes, and 2 forms of feed (mash or pellets).
      Data were collected to determine live performance, digestibility of the feed, and
      carcass composition. The daily amount of feed did not affect the ME of the feed,
      but broilers fed limited amounts of feed gained less BW per day and had a larger
      feed:gain ratio. For most measurements, strain of broiler, sex, and form of feed
      also were significant factors. Because broilers that gained BW more slowly
      required more days to gain 1.1 kg and more feed during that time, a larger
      proportion of the energy was used for maintenance. The net energy theory proposes
      that heat increment, net energy for maintenance, and net energy for production
      are constants for a feed ingredient or feed. Results from the present research
      did not support the net energy theory. A different model was proposed that used
      ME as the basis for energy partitioning. Amounts of feed or energy per day had no
      effect on the ME content of the feed; however, amounts of energy consumed per day
      had dramatic effects on the proportion of the ME from each gram of feed that was
      used for maintenance, product, or heat increment. A model was developed that
      showed these effects and the feed:gain ratio over a wide range of daily energy
      intake.

PMID- 19096064
TI  - Changes of biochemical parameters and enzyme activities in broiler chickens with
      cold-induced ascites.
AB  - An experiment with 250 one-day-old male broilers (Ross 308) was conducted to
      investigate the differences of some blood parameters of cold-induced ascitic and
      healthy broiler chicks in a 6-wk period. The chickens were divided into 2 groups
      of 5 replicates each. One group of these chickens was raised in normal
      temperature (NT) treatment and the other in cold temperature (CT) treatment to
      induce ascites. Mortality was necropsied daily to determine cause of death. At
      the end of the experiment (wk 6), 5 chickens from each replicate were randomly
      selected and slaughtered. The heart was removed; the right ventricle was
      dissected away from the left ventricle and septum. Weights of right and left
      ventricles were determined separately. Average BW gain and average feed intake
      were measured weekly, and weekly average feed conversion ratio was calculated.
      Serum glucose, total protein, cholesterol, triglyceride, activity of lactate
      dehydrogenase, as-partate aminotransferase, and alanine aminotransferase were
      determined. Throughout the study, the right ventricle-to-total ventricle ratio
      and total mortality percentage due to ascites of CT-treated birds at the end of
      experiment was greater (P < or = 0.05) than those of NT-treated ones. Fasting
      blood sugar of CT-treated birds in wk 4 and 6 was greater (P < or = 0.05) than NT
      treated birds. Total blood protein of CT treatment was lower than NT-treated
      birds in every week and whole period, but this difference was only significant (P
      < or = 0.05) in wk 6. There was not a significant difference between 2 treatments
      for triglyceride and cholesterol, lactate dehydrogenase, aspartate
      aminotransferase, and alanine aminotransferase. It was concluded that cold
      induced ascites could affect serum protein and fasting blood sugar of broiler
      chickens.

PMID- 19096065
TI  - Effect of enzyme supplementation and acidification of diets on nutrient
      digestibility and growth performance of broiler chicks.
AB  - Two experiments were conducted to examine the effects of alpha-galactosidase
      supplementation and acidification of diets on nutrient digestibility and growth
      performance of broiler chicks. In experiment 1, dietary treatments consisted of
      feeding a low-energy basal diet (2.74 Mcal of ME/kg) alone, the basal diet
      supplemented with 1,724 units of alpha-galactosidase per kg, the basal diet
      supplemented with 2% citric acid, or the basal diet supplemented with both. alpha
      Galactosidase significantly increased feed intake, weight gain, AME(n) of the
      diets, and retention of CP and neutral detergent fiber (NDF) (P < 0.05). Citric
      acid significantly increased the retention of DM, CP, and NDF, but decreased feed
      intake and weight gain. The greatest values for DM and NDF retention and for
      AME(n) were obtained with the combination of alpha-galactosidase plus citric
      acid. In experiment 2, chicks were fed diets with 2 levels of energy (2.74 or
      3.11 Mcal/kg), 2 levels of citric acid (0 or 1.5%), and 2 levels of alpha
      galactosidase (0 or 1,724 units/kg) in a 2 x 2 x 2 factorial arrangement of
      treatments. alpha-Galactosidase significantly increased the reducing sugar
      concentration in the crop content, whereas citric acid decreased the pH and
      increased the reducing sugar concentration in the crop content. Citric acid
      decreased the gain to feed ratio in the absence but not in the presence of alpha
      galactosidase. The data from these studies indicate that acidification of diet
      improves the efficacy of alpha-galactosidase.

PMID- 19096066
TI  - Organic trace minerals and 25-hydroxycholecalciferol affect performance
      characteristics, leg abnormalities, and biomechanical properties of leg bones of
      turkeys.
AB  - Leg problems and resulting mortality can exceed 1% per week in turkey toms
      starting at approximately 15 wk of age. Dietary supplementation of organic trace
      minerals (MIN) and 25-hydroxycholecalciferol (HyD) may improve performance,
      decrease incidence of leg abnormalities, and increase bone strength. Nicholas
      85X700 toms were assigned to 4 treatments consisting of a factorial arrangement
      of 2 concentrations of MIN (0 and 0.1% of Mintrex P(Se), which adds 40, 40, 20,
      and 0.3 mg/kg of Zn, Mn, Cu, and Se, respectively) and 2 concentrations of HyD (0
      and 92 microg/kg of HyD). Diets were formulated to be equal in nutrient content
      and fed ad libitum as 8 feed phases. Feed intake and BW were measured at 6, 12,
      15, 17, and 20 wk of age. Valgus, varus, and shaky leg defects were determined at
      12, 15, 17, and 20 wk of age. Tibia and femur biomechanical properties were
      evaluated by torsion and bending tests at 17 wk of age. There were no treatment
      effects on BW. Only MIN significantly improved feed conversion ratio through to
      20 wk of age. Cumulative mortality at 3 wk of age was greater among the MIN
      birds, but it was lower by 20 wk (P = 0.085). The MIN decreased the incidence of
      varus defects at 17 wk of age; shaky leg at 12, 15, and 17 wk of age; and valgus
      defects at 15, 17, and 20 wk of age. There were no MIN x HyD interaction effects
      on individual gait problems. Maximum load and the bending stress required for
      tibias to break in a 4-point assay were increased with MIN supplementation,
      especially when HyD was also added. Maximum shear stress at failure of femoral
      bones in a torsion assay was increased by supplementation with both MIN and HyD
      together. Dietary supplementation of MIN and HyD may improve biomechanical
      properties of bones. Dietary MIN supplementation may improve feed conversion of
      turkeys, likely by decreasing leg problems.

PMID- 19096067
TI  - Effects of diet type and enzyme addition on growth performance and gut health of
      broiler chickens during subclinical Clostridium perfringens challenge.
AB  - The effects of diet type (corn- vs. wheat-based) and multicarbohydrase addition
      on growth performance, digesta pH and viscosity, intestinal populations of
      Clostridium perfringens and lactic acid bacteria, and gut lesion score (from 0 to
      4, where 0 = no gross lesions, 4 = severe extensive necrosis) of broiler chickens
      during oral challenge with C. perfringens (none or 10(8) cfu/bird on d 13) were
      studied in a 39-d experiment. A total of 1,216 male Ross-308 chickens was
      assigned to 8 dietary treatments in a randomized complete block design providing
      8 replicate pens per treatment. Diets were formulated to meet the NRC protein
      requirement but were suboptimal in energy level. When compared with birds fed
      corn-based diets, chickens fed wheat-based diets had inferior (P < 0.01) final BW
      (2.49 vs. 2.59 kg) and feed conversion ratio (FCR; 1.83 vs. 1.78). Pathogen
      challenge significantly (P < 0.05) impaired growth performance and increased C.
      perfringens numbers and average lesion score. Increased (P < 0.01) C. perfringens
      counts (2.4 vs. 1.5 log(10) cfu/g of digesta) and intestinal lesion score (0.9
      vs. 0.4) were observed for challenged birds fed wheat-based diets. No difference
      in digesta pH and lactic acid bacteria numbers were found among the treatments.
      Enzyme addition to both the corn- and wheat-based diets increased bird final BW
      (2.57 vs. 2.51 kg; P < 0.01), decreased overall FCR (1.78 vs. 1.83; P < 0.01),
      and, in those consuming wheat-based diets, reduced digesta viscosity (from 4.1 to
      2.7 mPa.s; P < 0.01). Enzyme supplementation assisted the challenged birds in
      maintaining their optimal growth performance by improving (P < 0.05) average
      daily gain (59.5 vs. 56.9 g) in those consuming corn-based diets and FCR (1.83
      vs. 1.90) in those consuming wheat-based diets to values similar to those
      observed in control birds (59.7 g/d and 1.84, respectively). In conclusion,
      enzyme addition improved growth performance and mitigated the negative effects of
      C. perfringens challenge.

PMID- 19096068
TI  - Interaction of dietary high-oleic-acid sunflower hulls and different fat sources
      in broiler chickens.
AB  - The effect of dietary fat sources (high-oleic-acid sunflower seeds, HOASS; palm
      oil, PO; and high-oleic-acid sunflower oil, HOASO) and high-oleic-acid sunflower
      hulls (HOAS hulls; 40 g/kg of diet) on performance, digestive organ size, fat
      digestibility, and fatty acid profile in abdominal fat and blood serum parameters
      was evaluated in chickens (from 1 to 21 d of age). Bird performance and digestive
      organ size were not affected by either dietary fat source or sunflower hull
      supplementation. Fat digestibility in birds fed diets enriched (HOASS and HOASO)
      in monounsaturated fatty acids (MUFA) was increased compared with those fed the
      PO diet. The addition of sunflower hulls did not modify fat digestibility. The
      fatty acids pattern of abdominal fat reflected the dietary fat profile. The
      greatest concentrations of C16:0 and C18:0 were found in birds fed PO diets. The
      C18:1n-9 content was increased in birds that received HOASS and HOASO diets
      compared with those fed PO diets. The greatest content of C18:2n-6 was observed
      in birds fed HOASS diets. The ratio of polyunsaturated fatty acid (PUFA) to MUFA
      was significantly increased in birds fed PO diets compared with those fed HOASS
      or HOASO diets. The addition of sunflower hulls to the diets resulted in a
      decrease of C18:2n-6 and PUFA concentrations and PUFA:MUFA ratio in abdominal
      fat. Dietary fat sources and sunflower hulls modify blood triglycerides and serum
      lipoproteins. A decrease in triglyceride concentrations was observed in birds fed
      HOASS diets compared with those fed PO and HOASO diets. The greatest
      concentrations of serum high density, very low density (VLDL), and low density
      lipoproteins were found in birds receiving HOASO, PO, and HOASS diets,
      respectively. The addition of sunflower hulls to the diets caused an increase of
      serum triglycerides and VLDL concentrations. The MUFA-enriched diets had lower
      triglyceride and VLDL concentrations than did diets rich in saturated fatty
      acids. However, the sunflower hull addition had the opposite effect.

PMID- 19096069
TI  - Feeding laying hens a bioavailable soy sterol mixture fails to enrich their eggs
      with phytosterols or elicit egg yolk compositional changes.
AB  - Coronary heart disease (CHD) is the leading cause of death in the United States.
      Elevated levels of plasma total cholesterol (TC), and particularly plasma low
      density lipoprotein-cholesterol (LDLC), are primary contributing factors to CHD.
      Dietary plant sterols (phytosterols) have been shown to significantly reduce
      plasma TC and LDLC in humans, primarily through inhibition of intestinal
      cholesterol absorption, and are potentially effective agents for reduction of CHD
      risk. Although a variety of phytosterol-containing foods are currently available,
      phytosterol-enriched eggs, which represent a potential value-added product, are
      conspicuously absent from the marketplace. Therefore, the objectives of this
      study were 1) to enrich shell eggs with phytosterols; and 2) to determine if
      feeding phytosterols to hens elicits egg compositional changes, particularly that
      of yolk cholesterol content. Sixteen 32-wk-old White Leghorn hens were fed a corn
      soy-based layer diet without (n = 8) or with (n = 8) 1 g of supplemental soy
      sterols/100 g of diet for 28 d.. Hen performance was determined on an individual
      basis, and 1 egg/hen per week was collected, processed, and analyzed for yolk
      cholesterol, CP, crude fat (CF), and phytosterol content. There was no effect (P
      > 0.05) of supplemental dietary phytosterols on 28-d weight gain, feed
      consumption, feed efficiency, plasma TC, hen-day egg production, egg weights, egg
      component weights, and yolk cholesterol, CP, and CF contents. Small amounts of
      campesterol were present in most of the eggs (average of 0.29 and 1.02 mg/yolk
      for control vs. soy sterol-fed hens, respectively; P < or = 0.05), whereas only 3
      of the 80 analyzed eggs contained trace amounts of beta-sitosterol and none
      contained any detectable stigmasterol. It was concluded that phytosterols are
      either poorly absorbed from the chicken intestine or, if they are absorbed, they
      are efficiently secreted back into the intestinal lumen, most likely via as yet
      uncharacterized adenosine triphosphate-binding cassette transporters.

PMID- 19096070
TI  - Expression and activity of the 5'-adenosine monophosphate-activated protein
      kinase pathway in selected tissues during chicken embryonic development.
AB  - The 5'-adenosine monophosphate-activated protein kinase (AMPK) is a highly
      conserved serine-threonine protein kinase and a key part of a kinase-signaling
      cascade that senses cellular energy status (adenosine monophosphate:adenosine
      triphosphate ratio) and acts to maintain energy homeostasis by coordinately
      regulating energy-consuming and energy-generating metabolic pathways. The
      objective of this study was to investigate aspects of the AMPK pathway in the
      liver, brain, breast muscle, and heart from d 12 of incubation through hatch in
      chickens. We first determined mRNA and protein expression profiles for a major
      upstream AMPK kinase, LKB1, which is known to activate (phosphorylate) AMPK in
      response to increases in the adenosine monophosphate:adenosine triphosphate
      ratio. Expression of LKB1 protein was greatest in the brain, which demonstrated
      tissue-specific patterns for phosphorylation. Next, AMPK subunit mRNA and protein
      expression profiles were determined. Significant changes in AMPK subunit mRNA
      expression occurred in all tissues from d 12 of incubation to hatch. Differences
      in the levels of active (phosphorylated) AMPK as well as alpha and beta subunit
      proteins were observed in all 4 tissues during embryonic development. Finally, we
      determined the protein level and phosphorylation status of an important
      downstream target for AMPK, acetyl-coenzyme A carboxylase. The expression of
      acetyl-co-enzyme A carboxylase and phosphorylated acetyl-coenzyme A was greater
      in the brain than the liver, but was undetectable by Western blotting in the
      breast muscle and heart throughout the period of study. Together, our results are
      the first to demonstrate the expression and activity of the AMPK pathway in key
      tissues during the transition from embryonic to posthatch development in
      chickens.

PMID- 19096071
TI  - Ontogenetic development of the uncinate processes in the domestic turkey
      (Meleagris gallopavo).
AB  - Uncinate processes extend off the vertebral ribs in most species of bird. The
      processes are a crucial component of ventilatory mechanics, being involved in
      inspiration and expiration. Here we examine the pattern of ossification of the
      uncinate processes using histochemistry and biomechanical testing in developing
      domestic turkeys (Meleagris gallopavo). Ossification begins just before hatching,
      and the processes are fully ossified in the adult bird. We suggest that the
      development of these processes is linked to the onset of air breathing and the
      increase in sternal mass that occurs after hatching.

PMID- 19096072
TI  - The relationship among age, yolk fatty acids content, and incubation results of
      broiler breeders.
AB  - This research was carried out to investigate the correlations among age, yolk
      fatty acids content, and incubation results of broiler breeders. Egg samples were
      obtained from Ross 308 broiler breeder parent stock at 28, 45, and 65 wk of age.
      A total of 1,800 eggs were used for incubation results of each age period. The
      mean values of hatchability of fertile eggs (H/F) were 94.04 +/- 0.42, 91.36 +/-
      1.08, 85.97 +/- 0.96%, values for hatchability of total eggs (H) were 92.00 +/-
      0.47, 83.61 +/- 1.23, 62.78 +/- 1.57%, and fertility ratios (F) were 97.83 +/-
      0.30, 91.50 +/- 0.54, and 73.00 +/- 1.55% at 28, 45, and 65 wk of age,
      respectively (P < 0.01). The mean values of early embryonic mortality and hatched
      chick weight were 2.73 +/- 0.27, 4.01 +/- 0.56, 8.93 +/- 0.89% and 36.58 +/-
      0.51, 42.47 +/- 0.48, 45.31 +/- 0.96 g, at 28, 45, and 65 wk of age, respectively
      (P < 0.01). Myristic acid and linoleic acid contents of yolk significantly
      decreased with increasing age of broiler breeder (P < 0.01). The mean yolk
      myristic acid contents were 0.34 +/- 0.02, 0.29 +/- 0.06, and 0.24 +/- 0.01 mg/g,
      and linoleic acid contents were 21.60 +/- 1.26, 16.05 +/- 3.04, and 13.87 +/-
      0.49 mg/g at 28, 45, and 65 wk of age, respectively (P < 0.01). Correlations
      between breeder age and myristic acid and linoleic acid (r = -0.317 and -0.435,
      respectively) were significant when data were pooled from 28 to 65 wk of age.
      Significant correlations between H/F and myristic acid and linoleic acid were
      determined. The correlation between F and linoleic acid (r = 0.364; P < 0.05) was
      found to be significant with the change of breeder age. There were negative
      correlations between late embryonic mortality and myristic acid (r = -0.432; P <
      0.05), stearic acid (r = -0.437; P < 0.05), and linoleic acid (r = -0.469; P <
      0.5) at 28 to 65 wk of age. The findings from this study will contribute to the
      hatcheries of the poultry sector and the new studies that are going to be carried
      out..

PMID- 19096073
TI  - Exposure duration to long day lengths associated with the expression of
      photorefractoriness in turkey breeder hens.
AB  - In addition to inducing egg production, exposure to long days concomitantly
      activates processes that eventually result in photorefractoriness (PR) and
      cessation of egg production. Experiments were conducted to evaluate the duration
      of exposure to long days that result in these processes. In each of 3
      experiments, we subjected Large White turkey breeder hens to long days (16 or 18
      h per day) for differing lengths of time from initial photostimulation and then
      returned them to a photoperiod (12L:12D) that provided sufficient, but decreased,
      photoperiodic drive to support egg production but not induce PR.
      Photoresponsiveness was then evaluated by egg production after a return to a
      longer day length (20 h per day) late in the lay period and beyond the mean onset
      of PR typical for these turkey hens. Hens that have undergone any reduction in
      photoresponsiveness should not increase egg production in response to the
      increased photoperiod. From experiments 1 and 2, exposure to long days for as
      little as 1 d and as much as 9 wk from initial photostimulation did not result in
      an alteration in subsequent photoresponsiveness. This was based on an increased
      egg production response to a change in photoperiod from 12L:12D to 20L:4D after
      20 wk of photostimulation that was similar to controls held continuously on
      12L:12D and opposite to the response of controls held continuously on 18L:6D. It
      was clear that PR had been fully programmed by 20 wk of exposure to long days.
      Exposure to long days for 12 wk (experiment 3) resulted in a partial alteration
      of subsequent photoresponsiveness. It was concluded that programming of PR during
      late spring-summer season occurs after 9 wk of long day exposure, is not fully
      expressed by 12 wk of long days, and can be fully expressed by 20 wk of
      photostimulation.

PMID- 19096074
TI  - In vitro effects of alpha toxin from Clostridium perfringens on the
      electrophysiological parameters of jejunal tissues from laying hens preincubated
      with inulin and N-acetyl-L-cysteine.
AB  - The present report demonstrates the effect of alpha toxin from Clostridium
      perfringens on electrophysiological indexes of jejunal mucosa from laying hens
      pretreated with inulin and N-acetyl-l-cysteine (ACC), a mucolytic agent. In a
      first set of experiments, the effect of alpha toxin with or without pretreatment
      with ACC on the electrophysiological parameters was determined when jejunal
      tissues from laying hens were mounted in Ussing chambers. The short-circuit
      current remained unchanged when alpha toxin was added mucosally in the tissues
      whether pretreated with ACC or not. The change in the transmural tissue
      conductance (DeltaGt) was higher (P = 0.18) after 90 min exposure of toxin
      independent of pretreament with ACC. The effect of alpha toxin on DeltaGt became
      significant (P < or = 0.05) after 120 min of incubation. In the second set of
      experiments, the effect of alpha toxin on the jejunal tissues preincubated with
      inulin (0.1%) was investigated. The effect of toxin was also time dependent, and
      DeltaGt became significantly higher (P < or = 0.05) after 120 min of incubation
      independent of preinubation with inulin. Inulin did not influence the DeltaGt
      during the experimental period when compared with control tissues. In conclusion,
      alpha toxin from C. perfringens can impair the intestinal mucosal barrier. The
      effect is obviously not dependent on the presence of a mucolytic agent nor can it
      be affected by direct addition of inulin under in vitro conditions. Whether there
      is an effect of inulin after long-term supplementation in feeding trials or it is
      due to fermentation bacterial metabolites remains an open question.

PMID- 19096075
TI  - Fate of Listeria monocytogenes in ready-to-eat turkey breast rolls formulated
      with antimicrobials following electron-beam irradiation.
AB  - The objective of this study was to determine the effect of antimicrobials on the
      survival and proliferation of Listeria monocytogenes in turkey breast rolls
      following electron-beam irradiation. Six antimicrobial additive treatments that
      include no preservatives (control), 0.1% potassium benzoate (PB), 2% sodium
      lactate (SL), 0.1% potassium benzoate plus 2% sodium lactate (PB + SL), 2% sodium
      lactate plus 0.1% sodium diacetate (SL + SDA), and 0.1% potassium benzoate, 2%
      sodium lactate, and 0.1% sodium diacetate (PB + SL + SDA) were used. Sliced
      turkey breast rolls were artificially inoculated with approximately 10(6)
      cfu/cm(2) of 5-strain L. monocytogenes cocktails, then vacuum-packaged and
      irradiated at 0, 1.0, 1.5, 2.0, or 2.5 kGy. The radiation dose (kGy) that results
      in 90% reduction of viable cells for breast rolls, D(10) value, with various
      additive treatments ranged from 0.56 to 0.58 kGy. Adding PB (0.1%) or SL (2%) in
      turkey rolls failed to prevent L. monocytogenes from growing during refrigerated
      storage. In turkey rolls added with 2 (PB + SL or SL + SDA) or 3 (PB + SL + SDA)
      antimicrobial combinations had 2 or 3 wk of lag phases before L. monocytogenes
      growth, respectively. Irradiating turkey rolls, which were added with PB + SL or
      SL + SDA, at 1.0 kGy was effective in suppressing the growth of L. monocytogenes
      for about 6 wk when stored at 4 degrees C. No growth of L. monocytogenes after
      irradiation occurred during 42 d of storage for 2.0 kGy irradiated breast rolls
      formulated with 0.1% PB + 2% SL, 2% SL + 0.1% SDA or 0.1% PB + 2% SL + 0.1% SDA,
      and 1.0 kGy irradiated turkey breast with 0.1% PB + 2% SL + 0.1% SDA. Sensory
      panelists found that low-dose irradiation (1.0 kGy) had no effect on the sensory
      characteristics of ready-to-eat turkey breast rolls. Including SL + SDA had
      slightly negative effect for nonirradiated turkey breast rolls, but the sensory
      characteristics of 1.0 kGy irradiated turkey roll containing SL + SDA was not
      significantly different from the others receiving 1.0 kGy irradiation. For
      microbial safety, PB + SL and SL + SDA antimicrobial treatments combined with 1.0
      kGy or 2.0 kGy irradiation are a promising technology.

PMID- 19096076
TI  - Variation and Pearson correlation coefficients of Warner-Bratzler shear force
      measurements within broiler breast fillets.
AB  - Measurements of texture properties related to tenderness at different locations
      within deboned broiler breast fillets have been used to validate techniques for
      texture analysis and establish correlations between different texture evaluation
      methods. However, it has been demonstrated that meat texture can vary from
      location to location within individual muscles. The objective of our study was to
      investigate the intramuscular variation and Pearson correlation coefficients of
      Warner-Bratzler (WB) shear force measurements within early deboned broiler breast
      fillets and the effect of deboning time and cold storage on the variation and
      correlation coefficients. Broiler breast fillets were removed from carcasses
      early postmortem (2 h) and later postmortem (24 h). Storage treatments of the 2 h
      samples included 0 d, 7 d at 3 degrees C, 7 d at -20 degrees C, and 6 d at -20
      degrees C plus 1 d at 3 degrees C. The WB shears of cooked fillets were measured
      using a TA-XTPlus Texture Analyzer and a TA-7 WB shear type blade. Our results
      showed that although the average WB shear force values differed within the 0-d, 2
      h fillets, compared with the variation among the fillets within the treatment,
      the difference within a fillet is still evidently small. The Pearson correlation
      coefficients were significant between the locations; however, values of the
      correlation coefficients depended on the paired locations. Location differences
      in the WB shear values and the correlation coefficient values between them
      changed with deboning time and cold storage. These results demonstrate that the
      variation of WB shear force measurements is substantial within early deboned
      broiler breast fillets and the Pearson correlation coefficient values of the
      measurements vary among the locations. Both the variation and the Pearson
      correlation coefficients can be affected by postmortem aging time and storage.
      The differences in the means between the locations in early deboned breasts are
      much smaller than the variation among the fillets.

PMID- 19096077
TI  - Composition of intramuscular phospholipids and free fatty acids in three kinds of
      traditional Chinese duck meat products.
AB  - Composition of intramuscular phospholipids and free fatty acids in 3 kinds of
      traditional Chinese duck meat products (dry-cured duck, roasted duck, and water
      boiled salted duck) was investigated. Phospholipids were identified and
      quantified by HPLC combined with ultraviolet and evaporative light scattering
      detectors. The types and quantities of free fatty acids and fatty acids derived
      from phospholipids were analyzed by capillary gas chromatography. The results
      showed that raw duck meat had high quantities of phosphatidyl-ethanolamine and
      phosphatidylcholine (28.1 and 64.7% of total phospholipids, respectively), which
      contained high percentages of polyunsaturated fatty acids. The percentages of
      total phospholipids, phosphatidylethanolamine, and phosphatidylcholine decreased
      during processing, with a concomitant increase in quantities of free fatty acids.
      A selective degradation of fatty acids distributions of phospholipids was found
      through the dry-cured duck processing, but was not found during the roasted and
      water-boiled duck processing.

PMID- 19096078
TI  - Characterization of energetic efficiency in adult broiler breeder hens.
AB  - This trial characterized residual feed intake (RFI) and residual maintenance
      requirement (RME(m)) as measures of energetic efficiency in broiler breeder hens.
      The RFI was defined as the difference between observed and expected ME intake and
      RME(m) as the difference between observed and expected maintenance requirements.
      A total of 600 Ross 708 1-d-old pullets were placed in floor pens. At 16 wk, 144
      hens were caged and randomly assigned to 1 of 2 feed allocation treatments (72
      birds each). The control treatment had feed allocated on a group basis (GRP)
      following the standard BW target. A second treatment had feed allocated on an
      individual-bird basis (IND) and followed the same BW target as GRP. Sexual
      maturity age, egg and chick production, and several feed conversion ratios were
      correlated to standardized efficiency indices of RFI (SRFI) and RME(m) (SRME(m))
      in each treatment. Greater SRFI and SRME(m) values described a greater energetic
      efficiency. Residual feed intake was more variable in IND than GRP hens (P <
      0.001). The variability of RME(m) did not differ between treatments (P = 0.14).
      The SRFI was positively correlated to egg production in the GRP hens (r = 0.31),
      but negatively correlated in IND hens (r = -0.40) and was correlated to feed
      conversion per chick only in the GRP-based feed allocation (r = -0.44). The
      SRME(m) correlated strongly to egg production (r = 0.64), chick production (r =
      0.64), and feed conversion per chick (r = -0.59) in both feed allocation
      treatments. Feed intake confounded the RFI calculation, which limits the value of
      RFI as a selection criterion in meat-producing animals. The independence of
      RME(m) from feed intake is desirable for energetic efficiency assessment in
      selection programs because consistent values can be obtained across different
      management schemes. Hens with lower maintenance requirements (greater RME(m)
      efficiency) partitioned more energy toward reproduction than did high-maintenance
      hens. The RME(m) methodology provided an unbiased estimate of energetic
      efficiency by adjusting the maintenance requirement for the effect of dietary
      thermogenesis.

PMID- 19096079
TI  - Effects of maternal energetic efficiency on egg traits, chick traits, broiler
      growth, yield, and meat quality.
AB  - This study assessed egg traits, chick traits, growth, yield, and meat quality
      characteristics of the offspring from broiler breeders classified by 2
      measurements of energetic efficiency: residual feed intake (RFI), defined as the
      difference between observed and expected ME intake, and residual maintenance
      requirement (RME(m)), defined as the residual of the relationship between hen
      maintenance requirement and feed intake. A group of 72 pullets were placed in
      laying cages from 16 to 60 wk of age. Individual hen-based feed allocation was
      provided following a standard BW target. At 41wk, eggs from 8 d of production
      were collected and pedigree hatched. Chicks were assigned to 1 of 3 maternal RFI
      (RFI(mat)) categories: low, average, and high. A total of 366 chicks were placed
      in 36 floor pens, 6 per sex x RFI(mat) interaction, and raised to 38 d. At the
      end of the breeder experiment (60 wk), broilers were retrospectively assigned to
      a low or high maternal RME(m) (RME(mmat)) category. Low RFI(mat) broilers had
      greater 38-d BW than average and high RFI(mat) broilers. That was achieved
      through a greater BW gain and feed intake of low RFI(mat) broilers from 21 to 28
      d. It was found that RFI(mat) had no effect on feed conversion, yield, or meat
      quality characteristics. Low RME(m) hens produced heavier eggs (62.3 g) and
      chicks (42.5 g) than high RME(m) hens (60.0 g; 41.0 g), but RME(mmat) did not
      affect broiler 38-d BW. High RME(mmat) broilers had greater breast yield (29.5%)
      and lower breast shear force (4.7 kg of force/g) than low RME(mmat) broilers
      (28.5%; 5.6 kg of force/g). The low RFI(mat) x high RME(mmat) broilers had the
      greatest growth to 38 d. It was found that RFI(mat) was inversely related to
      broiler growth, particularly when RME(mmat) was high. Although low maintenance
      requirements may be desirable for egg and chick production, hens with a high
      maintenance requirement produced broilers with greater breast yield and
      tenderness. Minimizing maintenance requirements may not be compatible with
      maximizing broiler performance and meat yield.

PMID- 19096080
TI  - Molecular predictors for anaemia after kidney transplantation.
AB  - BACKGROUND: Anaemia of chronic kidney disease is a well-studied comorbidity, but
      the molecular predictors of post-transplant anaemia remain elusive. METHODS: In
      this case-control study, 25 subjects with post-transplant anaemia, defined as
      erythropoiesis-stimulating agent (ESA) requirement within the first post
      transplant year, were matched to 25 control recipients with comparable
      demographics but no anaemia using the Austrian Dialysis and Transplant Registry.
      Genome-wide gene expression analyses of deceased donor kidney biopsies obtained
      immediately before engraftment were performed using custom cDNA microarrays.
      Significant molecular features were included together with clinical variables in
      a multivariable logistic regression analysis and further analysed with respect to
      their molecular functions, biological processes and cellular locations using gene
      ontology terms and protein-protein interactions. RESULTS: Immunity response
      molecules were over-represented in the up-regulated gene list suggesting the
      involvement of the inflammation cascade as a predictor of ESA requirement after
      engraftment. From the initial list of the 34 differentially expressed genes, we
      identified the best three genes predicting ESA requirement in the first year by a
      stepwise gene selection algorithm. SPRR2C (OR = 0.24, 95% CI 0.07-0.85, P =
      0.027) and GSTT1 (OR = 2.40, 95% CI 1.21-4.77, P = 0.013) remained significant
      after adjusting for donor age, eGFR, BCAR and CRP. CONCLUSION: In summary, we
      identified three biomarkers (SPRR2C, B3GALTL and GSTT1) of post-transplant
      anaemia in donor kidney biopsies that correctly predicted ESA requirement within
      the first year after transplantation in 93% of the cases.

PMID- 19096081
TI  - Disruption of the Smad7 gene promotes renal fibrosis and inflammation in
      unilateral ureteral obstruction (UUO) in mice.
AB  - BACKGROUND: The present study tested the hypothesis that disruption of Smad7
      function may accelerate renal fibrosis and inflammation. METHODS: This was
      investigated in a unilateral ureteral obstruction (UUO) model induced in wild
      type (WT) and Smad7DeltaE1 mice in which functional Smad7 is disrupted by
      deleting exon I in the Smad7 gene. Renal fibrosis and inflammation after UUO were
      examined by histology, real-time PCR, western blot analyses and
      immunohistochemistry. RESULTS: Seven days after UUO, severe tubulointerstitial
      fibrosis developed in WT mice as evidenced by a marked increase in alpha-SMA,
      collagen I and III extracellular matrix. This was associated with a significant
      upregulation of renal TGF-beta1 and CTGF and activation of Smad2/3.
      Interestingly, compared to WT UUO mice, Smad7DeltaE1 mice with UUO exhibited a
      further increase in TGF-beta/Smad2/3-dependent renal fibrosis. Moreover, compared
      to WT UUO mice, deletion of the Smad7 gene also sustained NF-kappaB activation
      and thus enhanced further renal inflammation such as macrophage infiltration and
      upregulation of TNF-alpha, MCP-1, OPN and ICAM-1. CONCLUSION: Smad7 is a critical
      negative regulator of TGF-beta/Smad2/3 and NF-kappaB signalling and plays a
      negative regulating role in both renal fibrosis and inflammation after UUO.
      Results from this study further support the notion that Smad7 may be a
      therapeutic agent for kidney diseases.

PMID- 19096082
TI  - Athrombocytopenic thrombotic microangiopathy, a condition that could be
      overlooked based on current diagnostic criteria.
AB  - BACKGROUND: Thrombotic thrombocytopenic purpura (TTP) and haemolytic uraemic
      syndrome (HUS) are thrombotic microangiopathies (TMAs). They are generally
      diagnosed and treated by plasmapheresis in the presence of non-immune haemolytic
      anaemia and thrombocytopenia. Yet, many individuals admitted in our hospital for
      athrombocytopenic renal failure of unknown cause were reported to have TMA as
      main lesion on kidney biopsies. METHODS: Speculating that this presentation is
      not uncommon and that the underlying lesion might not be suspected because of
      current diagnostic criteria, we determined its prevalence and other accompanying
      features through a retrospective single-centre cohort of 50 cases where TMA had
      been identified histologically. RESULTS: At presentation, normal serum platelets
      were common (44%) but still accompanied by abnormal serum LDH in most subjects.
      End-stage renal disease and mortality at 5 years were also high especially in the
      athrombocytopenic group, but unrelated to the underlying aetiology of TMA.
      Importantly, several subjects in both groups received and apparently responded to
      plasmapheresis. CONCLUSION: In the absence of thrombocytopenia, TMA should still
      be contemplated when renal failure is associated with high serum LDH and its
      possible treatment with plasmapheresis assessed through prospective trials.

PMID- 19096083
TI  - Frequencies of hepatitis B and C infections among haemodialysis and peritoneal
      dialysis patients in Asia-Pacific countries: analysis of registry data.
AB  - BACKGROUND: The impact of dialysis modality on the rates and types of infectious
      complications has not been well studied. The aim of the present investigation was
      to evaluate the rates of hepatitis C virus (HCV) and hepatitis B virus (HBV)
      infections in peritoneal dialysis (PD) and haemodialysis (HD) patients in the
      Asia-Pacific region. METHODS: The study included the most recent period-prevalent
      data recorded in the national or regional dialysis registries of the 10 Asia
      Pacific countries/areas (Australia, New Zealand, Japan, China, Taiwan, Korea,
      Thailand, Hong Kong, Malaysia and India), where such data were available.
      Longitudinal data were also available for all incident Australian and New Zealand
      patients commencing dialysis between 1 April 1995 and 31 December 2005. Rates of
      HCV and HBV infections were compared by chi-square, Poisson regression and Kaplan
      Meier survival analyses, as appropriate. RESULTS: Data were obtained on 201,590
      patients (HD 173,788; PD 27,802). HCV seroprevalences ranged between 0.7% and
      18.1% across different countries and were generally higher in HD versus PD
      populations (7.9% +/- 5.5% versus 3.0% +/- 2.0%, P = 0.01). Seroconversion rates
      on dialysis were also significantly higher in HD patients (incidence rate ratio
      PD versus HD 0.33, 95% CI 0.13-0.75). HCV infection was highly predictive of
      mortality in Japan (relative risk 1.37, 95% CI 1.15-1.62, P = 0.003) and in
      Australia and New Zealand (adjusted hazards ratio 1.29, 95% CI 1.05-1.58). HBV
      infection data were limited, but less clearly influenced by dialysis modality.
      CONCLUSIONS: Dialysis modality selection significantly influences the risk of HCV
      infection experienced by end-stage renal failure patients in the Asia-Pacific
      region. No such association could be identified for HBV infection.

PMID- 19096084
TI  - Characteristics of dialysis-related amyloidosis in patients on haemodialysis
      therapy for more than 30 years.
AB  - BACKGROUND: Dialysis-related amyloidosis is one of the chronic the complications
      of haemodialysis. We conducted an investigation of dialysis-associated
      amyloidosis in extremely long-term survivors. METHODS: Twenty-one patients on
      haemodialysis for more than 30 years ('30+' group) and 13 patients on
      haemodialysis for 20-30 years ('20-30' group) at Sangenjaya Hospital were
      enrolled in this study. The frequencies of operations for conditions related to
      haemodialysis-related amyloidosis were examined. RESULTS: The mean age at the
      start of haemodialysis was younger in the '30+' group (29.1 +/- 7.3 years) than
      in the '20-30' group (40.5 +/- 8.2 years, P = 0.0003). Eighteen (85.7%) patients
      had undergone surgery for CTS, six (28.6%) had undergone surgery for trigger
      finger and six (28.6%) had undergone surgery for cervical destructive
      spondyloarthropathy (DSA) at 30 years after the start of haemodialysis therapy.
      Patients who were over the age of 30 years at the start of dialysis therapy more
      frequently underwent CTS operations (100%) than those who were under 30 years of
      age at the start of dialysis (76.9%; P = 0.025) in the '30+' group at 30 years
      after the start of haemodialysis. The frequencies of operations for CTS did not
      differ significantly between the '20-30' group and the '30+' group. CONCLUSIONS:
      Haemodialysis-associated amyloidosis was common in extremely long-term survivors.
      Even though the mean age at the start of haemodialysis was younger in the '30+'
      group than in the '20-30' group, the frequency of operations for CTS did not
      differ. This may be attributable to the recent advances in haemodialysis
      technologies.

PMID- 19096085
TI  - Development of an affordable dye-stained microalbuminuria screening test.
AB  - BACKGROUND: A simple spot test was developed, which allows quantification of
      microalbuminuria. Evaluation was carried out according to the ISO 15189
      guidelines. METHODS: Urine was spotted on cellulose acetate strips and stained
      using different sensitive protein binding dyes (nigrosin, Coomassie Blue R-250,
      amido black). The colour intensity of the stained spots was quantified using a
      Kodak Image 450 station. RESULTS: Analytical sensitivity of the Coomassie Blue
      based method (18 mg/L) was better than that for nigrosin (50 mg/ L) or amido
      black (100 mg/L) based methods. Within-run coefficient of variation (CV) and
      between-run CV of the Coomassie blue assay were, respectively, 8.4% and 9.7% (50
      mg/L), and 3% and 4.5% (400 mg/L). For nigrosin, these data were, respectively,
      8.4 and 9.4 (50 mg/L), and 3.4 and 6.4% (400 mg/L). Coomassie Blue showed a
      preferential binding selectivity towards albumin. The method was found to be
      linear between 20 and 600 mg/L. A good correlation (r2 = 0.89) was obtained
      between Coomassie Blue based and immunonephelometric measurements. Immuno
      unreactive albumin (prepared by protease treatment) could be detected by the spot
      test, which offers an advantage of the method versus immunochemical tests.
      Ammonium sulphate precipitation could further increase the specificity of the
      assay by eliminating effects of free light chains. CONCLUSION: The described
      method is very simple and extremely cheap, which makes it potentially suited for
      screening programmes, particularly in third world countries.

PMID- 19096086
TI  - Phenotype-genotype correlation in antenatal and neonatal variants of Bartter
      syndrome.
AB  - BACKGROUND: Ante/neonatal Bartter syndrome (BS) is a hereditary salt-losing
      tubulopathy due to mutations in genes encoding proteins involved in NaCl
      reabsorption in the thick ascending limb of Henle's loop. Our aim was to study
      the frequency, clinical characteristics and outcome of each genetic subtype.
      METHODS: Charts of 42 children with mutations in KCNJ1 (n = 19), SLC12A1 (n = 13)
      CLCNKB (n = 6) or BSND (n = 4) were retrospectively analysed. The median follow
      up was 8.3 [0.4-18.0] years. RESULTS: We describe 24 new mutations: 10 in KCNJ1,
      11 in SLC12A1 and 3 in CLCNKB. The onset of polyhydramnios, birth term, height
      and weight were similar for all groups; three patients had no history of
      polyhydramnios or premature birth and had CLCNKB mutations according to a less
      severe renal sodium wasting. Contrasting with these data, patients with CLCNKB
      had the lowest potassium (P = 0.006 versus KCNJ1 and P = 0.034 versus SLC12A1)
      and chloride plasma concentrations (P = 0.039 versus KCNJ1 and P = 0.024 versus
      SLC12A1) and the highest bicarbonataemia (P = 0.026 versus KCNJ1 and P = 0.014
      versus SLC12A1). Deafness at diagnosis was constant in patients with BSND
      mutations; transient neonatal hyperkalaemia was present in two-thirds of the
      children with KCNJ1 mutations. Nephrocalcinosis was constant in KCNJ1 and SLC12A1
      but not in BSND and CLCNKB patients. In most cases, water/electrolyte
      supplementation + indomethacin led to catch-up growth. Three patients developed
      chronic renal failure: one with KCNJ1 mutations during the second decade of age
      and two with CLCNKB and BSND mutations and without nephrocalcinosis during the
      first year of life. CONCLUSIONS: We confirmed in a large cohort of ante/ neonatal
      BS that deafness, transient hyperkalaemia and severe hypokalaemic hypochloraemic
      alkalosis orientate molecular investigations to BSND, KCNJ1 and CLCNKB genes,
      respectively. Chronic renal failure is a rare event, associated in this cohort
      with three genotypes and not always associated with nephrocalcinosis.

PMID- 19096087
TI  - A clinical score to predict 6-month prognosis in elderly patients starting
      dialysis for end-stage renal disease.
AB  - AIM: The aim of this study was to develop and validate a prognostic score for 6
      month mortality in elderly patients starting dialysis for end-stage renal
      disease. METHODS: Using data from the French Rein registry, we developed a
      prognostic score in a training sample of 2500 patients aged 75 years or older who
      started dialysis between 2002 and 2006, which we validated in a similar sample of
      1642 patients. Multivariate logistic regression with 500 bootstrap samples
      allowed us to select risk factors from 19 demographic and baseline clinical
      variables. RESULTS: The overall 6-month mortality was 19%. Age was not associated
      with early mortality. Nine risk factors were selected and points assigned for the
      score were as follows: body mass index <18.5 kg/m2 (2 points), diabetes (1),
      congestive heart failure stages III to IV (2), peripheral vascular disease stages
      III to IV (2), dysrhythmia (1), active malignancy (1), severe behavioural
      disorder (2), total dependency for transfers (3) and unplanned dialysis (2). The
      median score was 2. Mortality rates ranged from 8% in the lowest risk group (0
      point) to 70% in the highest risk group (> or =9 points) and 17% in the median
      group (2 points). Seventeen percent of all deaths occurred after withdrawal from
      dialysis, ranging from 0% for a score of 0-1 to 15% for a score of 7 or higher.
      CONCLUSIONS: This simple clinical score effectively predicts short-term prognosis
      among elderly patients starting dialysis. It should help to illuminate clinical
      decision making, but cannot be used to withhold dialysis. It ought to only be
      used by nephrologists to facilitate the discussion with the patients and their
      families.

PMID- 19096089
TI  - Declining sperm counts and increases in testicular cancer: a legacy of the cold
      war?

PMID- 19096088
TI  - Differential gene expression in the testes of different murine strains under
      normal and hyperthermic conditions.
AB  - Cryptorchidism and scrotal heating result in abnormal spermatogenesis, but the
      mechanism(s) prescribing this temperature sensitivity are unknown. It was
      previously reported that the AKR/N or MRL/MpJ-+/+ mouse testis is more heat
      resistant than the testis from the C57BL/6 strain. We have attempted to probe
      into the mechanism(s) involved in heat sensitivity by examining global gene
      expression profiles of normal and heat-treated testes from C57BL/6, AKR/N, and
      MRL/MpJ-+/+ mice by microarray analysis. In the normal C57BL/6 testis, 415 and
      416 transcripts were differentially expressed (at least 2-fold higher or lower)
      when compared with the normal AKR/N and MRL/MpJ-+/+ testis, respectively. The
      AKR/N and MRL/MpJ-+/+ strains revealed 268 differentially expressed transcripts
      between them. There were 231 transcripts differentially expressed between C57BL/6
      and 2 purported heat-resistant strains, AKR/N and MRL/MpJ-+/+. Next, the testes
      of C57BL/6 and AKR/N mice were exposed to 43 degrees C for 15 minutes and
      harvested at different time points for terminal deoxynucleotidyl transferase dUTP
      nick end labeling (TUNEL) studies and microarrays. An increase of TUNEL-positive
      germ cell numbers was significant 8 hours after heat exposure in the C57BL/6
      mouse. However, this increase was not observed in the AKR/N mouse until 10 hours
      after heat exposure. All tubules showed germ cell loss and disruption in C57BL/6
      testis 24 hours after heat shock. In contrast, although a number of seminiferous
      tubules showed an abnormal morphology 24 hours post-heat shock in the AKR/N
      mouse, many tubules still retained a normal structure. Numerous transcripts
      exhibited differential regulation between the 2 strains within 24 hours after
      heat exposure. The differentially expressed transcripts in the testes 8 hours
      after heat exposure were targeted to identify the genes involved in the initial
      response rather than those attributable to germ cell loss. Twenty transcripts
      were significantly down-regulated and 19 genes were up-regulated by hyperthermia
      in C57BL/6 and did not show a parallel change in the AKR/N testis. Conversely,
      heat shock resulted in 30 up-regulated transcripts and 31 down-regulated
      transcripts in AKR/N that were not similarly regulated in C57BL/6. A number of
      genes shared similar differential expression patterns and differential regulation
      by hyperthermia in both strains of mice. Taken together, the results of the
      present study indicate that the diverse genetic backgrounds in the 3 strains lead
      to major differences in normal testis gene expression profiles, whereas the
      differences in heat shock responses involve a significantly smaller number of
      genes. The data generated may provide insights regarding gene networks and
      pathways involved in heat stress and their relationship to spermatogenesis.

PMID- 19096090
TI  - Racial and ethnic disparities in antidepressant drug use.
AB  - BACKGROUND: Little is known about racial and ethnic disparities in health care
      utilization, expenditures and drug choice in the antidepressant market. AIMS:
      This study investigates factors associated with the racial and ethnic disparities
      in antidepressant drug use. We seek to determine the extent to which disparities
      reflect differences in observable population characteristics versus heterogeneity
      across racial and ethnic groups. Among the population characteristics, we are
      interested in identifying which factors are most important in accounting for
      racial and ethnic disparities in antidepressant drug use. METHODS: Using Medical
      Expenditure Panel Survey (MEPS) data from 1996-2003, we have an available sample
      of 10,416 Caucasian, 1,089 African American and 1,539 Hispanic antidepressant
      drug users aged 18 to 64 years. We estimate individual out-of-pocket payments,
      total prescription drug expenditures, drug utilization, the probability of taking
      generic versus brand name antidepressants, and the share of drugs that are older
      types of antidepressants (e.g., TCAs and MAOIs) for these individuals during a
      calendar year. Blinder-Oaxaca decomposition techniques are employed to determine
      the extent to which disparities reflect differences in observable population
      characteristics versus unobserved heterogeneity across racial and ethnic groups.
      RESULTS: Caucasians have the highest antidepressant drug expenditures and
      utilization. African-Americans have the lowest drug expenditures and Hispanics
      have the lowest drug utilization. Relative to Caucasians and Hispanics, African
      Americans are more likely to purchase generics and use a higher share of older
      drugs (e.g., TCAs and MAOIs). Differences in observable characteristics explain
      most of the racial/ethnic differences in these outcomes, with the exception of
      drug utilization. Differences in health insurance and education levels are
      particularly important factors in explaining disparities. In contrast,
      differences in drug utilization largely reflect unobserved heterogeneity across
      these population groups. CONCLUSIONS: Substantive racial and ethnic disparities
      exist in all dimensions of antidepressant drug use examined. Observable
      population characteristics account for most of the differences in the
      expenditures, with health insurance and education key factors driving differences
      in spending. Observable characteristics are also important in explaining racial
      and ethnic disparities in the probability of purchasing generics and new vs old
      antidepressant drugs used. Differences in total utilization are not well
      explained by observable characteristics, and may reflect unobserved heterogeneity
      such as unobserved physician-patient relationships, mistrust, and cultural
      factors. IMPLICATIONS FOR POLICY: Reducing differences in observable
      characteristics such as health insurance and education will mitigate racial and
      ethnic disparities in expenditures on antidepressant drug use and in the types of
      antidepressant used (e.g., generics vs. brands; new vs old). But these factors
      will have less influence in reducing racial and ethnic disparities in overall
      antidepressant drug utilization. To limit differences in overall antidepressant
      drug use, policymakers must take into account cultural factors and other sources
      of heterogeneity.

PMID- 19096091
TI  - Job loss, retirement and the mental health of older Americans.
AB  - BACKGROUND: Millions of older individuals cope with physical limitations,
      cognitive changes, and various losses such as bereavement that are commonly
      associated with aging. Given increased vulnerability to various health problems
      during aging, work displacement might exacerbate these due to additional distress
      and to possible changes in medical coverage. Older Americans are of increasing
      interest to researchers and policymakers due to the sheer size of the Baby Boom
      cohort, which is approaching retirement age, and due to the general decline in
      job security in the U.S. labor market. AIMS OF THE STUDY: This research compares
      and contrasts the effect of involuntary job loss and retirement on the mental
      health of older Americans. Furthermore, it examines the impact of re-employment
      on the depressive symptoms. METHODS: There are two fundamental empirical
      challenges in isolating the effect of employment status on mental health. The
      first is to control for unobserved heterogeneity--all latent factors that could
      impact mental health so as to establish the correct magnitude of the effect of
      employment status. The second challenge is to verify the direction of causality.
      First difference models are used to control for latent effects and a two-stage
      least squares regression is used to account for reverse causality. RESULTS: We
      find that involuntary job loss worsens mental health, and re-employment
      recaptures the past mental health status. Retirement is found to improve mental
      health of older Americans. DISCUSSION: With the use of longitudinal data from the
      Health and Retirement Study surveys and the adoption of proper measures to
      control for the possibility of reverse causality, this study provides strong
      evidence of elevating depressive symptoms with involuntary job displacement even
      after controlling for other late-life events. Women suffer from greater distress
      levels than men after job loss due to business closure or lay-off. However, women
      also exhibit better psychological well-being than men following retirement. The
      present study is the first to report that the re-employment of involuntary job
      loss sufferers leads to a recapturing of past mental health status. Additionally,
      we find that re-entering the labor force is psychologically beneficial to
      retirees as well. IMPLICATIONS FOR HEALTH CARE PROVISION: It is well established
      that out-of-pocket expenditures on all forms of health care for seniors with self
      diagnosed depression significantly exceeds expenditures for seniors with other
      common ailments such as hypertension and arthritis in the U.S. Thus, our research
      suggests that re-employment of older Americans displaced from the labor force
      will be cost-effective with regard to personal mental health outcomes.
      IMPLICATIONS FOR HEALTH POLICIES: That re-employment of involuntary job loss
      sufferers leads to a recapturing of past mental health status illuminates one
      potential policy trade off - increased resources dedicated to job training and
      placement for older U.S. workers could reap benefits with regard to reduced
      private and public mental health expenditures. IMPLICATIONS FOR FURTHER RESEARCH:
      Further research could more clearly assess the degree to which the mental health
      benefits of employment among older Americans would warrant the expansion of job
      training and employment programs aimed at this group.

PMID- 19096092
TI  - Insurance coverage and the treatment of mental illness: effect on medication and
      provider use.
AB  - BACKGROUND: Canada's public health insurance system fully covers medically
      necessary hospital and physician services, but does not cover community-based non
      physician mental health provider services or prescription drugs. Almost 2/3 of
      Canadians have private supplemental insurance for extended health benefits,
      typically through their employer, so its distribution is skewed to higher-income,
      employed Canadians, and typically features substantial cost-sharing and coverage
      limits. A recent national survey suggests only one-third of Canadians with
      selected mental disorders talked to a health professional during the previous 12
      months and only a minority (19.3%) receive drug treatment. Financial barriers to
      care constitute a potentially important contributor to this under-use of mental
      health treatments. AIMS OF THE STUDY: The objective is to understand how private
      supplemental insurance status affects the utilization of prescription medication
      and four types of community-based providers for mental health problems in Canada.
      METHODS: The data derive from a special mental health supplement to the
      nationally representative Canadian Community Health Survey. Utilization of five
      types of prescribed medications (sleep, anxiety, mood stabilizers, anti
      depressants and anti-psychotics) is measured dichotomously as use/no-use in the
      previous 12 months. Utilization of community-based provider services (family
      physician, psychiatrist, psychologist and social worker) is measured as (i)
      use/no-use and (ii) conditional on use, number of contacts in the previous 12
      months. We employ multivariate regression methods appropriate to the binary and
      count nature of the dependent variable to measure the impact of supplemental
      private insurance status on utilization, controlling for health, demographic and
      socio-economic characteristics. We test for endogeneity of insurance status using
      instrumental variable techniques. RESULTS: Having private supplemental insurance
      significantly increases the odds of using medications for mental illness, with
      particularly large increases for anti-psychotic and mood-stabilizer medications.
      Private supplemental insurance coverage does not increase use of provider
      services. We find little evidence of endogeneity of private insurance.
      DISCUSSION: Lack of supplemental insurance for prescription medication is a
      potentially important financial barrier to mental health treatment in Canada. The
      estimated effect is likely understated because the utilization measure does not
      capture quantity of medication use. It is not surprising that no significant
      relationship between private insurance status and utilization of provider
      services is found for publicly-covered family physician and psychiatry services,
      where the link between supplemental insurance and use is indirect, through the
      need to visit a physician to obtain a prescription. The result is surprising for
      psychologists and social workers, and may reflect limits to private coverage
      which are not fully captured here. IMPLICATIONS FOR HEALTH CARE PROVISION AND
      USE: Insurance coverage has an important relative impact on the likelihood of
      drug use for mental illness. IMPLICATIONS FOR HEALTH POLICIES: A program that
      offers insurance coverage for anti-psychotic and mood-stabilizing medication
      could reduce the high personal and societal burden associated with serious mental
      illness, without a large overall budgetary impact. IMPLICATIONS FOR FUTURE
      RESEARCH: Future research should incorporate insurance measures which capture
      details of coverage among all survey respondents. Linking survey to utilization
      data will help to overcome issues of recall bias.

PMID- 19096093
TI  - The Israeli mental health insurance reform--perspectives.
AB  - BACKGROUND: At present, Israel's mental health system functions separately from
      its physical health system in terms of financing, planning, organization and
      practice setting. The government is responsible for the provision of mental
      health care, while the country's four, competing, non-profit health plans are
      responsible for physical health care. A reform effort is underway to transfer
      legal responsibility for the provision of mental health care from the government
      to the health plans. AIMS: The main objectives of this paper are to summarize the
      key components of the reform, its objectives, and the concerns that it has
      raised. The paper also seeks to foster interactions between experts from Israel
      and other countries about the Israeli reform. METHODS: The analysis is based on
      official government documents, the scholarly literature about the Israeli reform
      and the relevant international literature about mental health care in other
      countries, participation in key public meetings related to the reform,
      discussions with leaders of the reform effort, and discussions with leading
      mental health experts in other countries. RESULTS: Two elements of the reform-
      the application of managed care principles to mental health and the integration
      of mental and physical care--are shown to be central both to the reform's
      objectives and to the concerns that have been raised about the reform.
      DISCUSSION: These same two elements are relevant to many countries implementing
      or considering reforms in their mental health systems. CONCLUSIONS: The
      architects of the Israeli reform could learn a great deal from the experience
      with mental health care and related reforms in other countries. At the same time,
      the Israeli reform could offer important insights and lessons for other
      countries. IMPLICATIONS FOR POLICY: The Government of Israel should work with the
      international mental health care professional community to create frameworks that
      would facilitate cross-national learning. IMPLICATIONS FOR FURTHER RESEARCH: It
      will be important to monitor the implementation of the reform and evaluate its
      impact, in order to assess the extent to which the objectives are met and the
      extent to which the concerns materialize. Cross-national research collaborations
      could be very helpful.

PMID- 19096094
TI  - The fifth conference of the International CoQ10 Association, Kobe 2007--50th
      anniversary of CoQ10 discovery. Introduction.

PMID- 19096095
TI  - The evolution of coenzyme Q.
AB  - In the 50 years since the identification of coenzyme Q as an electron carrier in
      mitochondria, it has been identified with diverse and unexpected functions in
      cells. Its discovery came as a result of a search for electron carriers in
      mitochondria following the identification of flavin and cytochromes by Warburg,
      Keilin, Chance and others. As a result of investigation of membrane lipids at
      D.E. Green's laboratory at University of Wisconsin coenzyme Q was identified as
      the electron carrier between primary flavoprotein dehydrogenases and the
      cytochromes. Then Peter Mitchell identified the role of transmembrane proton
      transfer as a basis for ATP synthesis. The general distribution of coenzyme Q in
      all cell membranes then led to the recognition of a role as a primary
      antioxidant. The protonophoric function was extended to acidification of Golgi
      and lysosomal vericles. A further role in proton release through the plasma
      membrane and its relation to cell proliferation has not been fully developed. A
      role in generation of H202 as a messenger for hormone and cytokine action is
      indicated as well as prevention of apoptosis by inhibition of ceramide release.
      Identification of the genes and proteins required for coenzyme Q synthesis has
      led to a basis for defining deficiency. For 50 years Karl Folkers has led the
      search for deficiency and therapeutic application. The development of large scale
      production, better formulation for uptake, and better methods for analysis have
      furthered this search. The story isn't over yet. Questions remain about effects
      on membrane structure, breakdown and control of cellular synthesis and uptake and
      the basis for therapeutic action.

PMID- 19096097
TI  - Function of a bound ubiquinone in Escherichia coli quinoprotein glucose
      dehydrogenase.
AB  - Membrane-bound glucose dehydrogenase (mGDH) is a single integral protein in the
      respiratory chain in Escherichia coli which oxidizes D-glucose and feeds
      electrons to ubiquinol oxidase via bulk ubiquinone (UQ). mGDH contains a bound
      UQ, CoQ8, for its intramolecular electron transfer in addition to
      pyrroloquinoline quinone (PQQ) as a coenzyme. Pulse radiolysis analysis revealed
      that the bound UQ exists very close to PQQ at a distance of 11-13 angstroms.
      Studies on mGDH mutants with substitutions for amino acid residues around PQQ
      showed that Asp-466 and Lys-493, which are crucial for catalytic activity,
      interact with bound UQ. Based on these findings, we propose that the bound UQ is
      involved in the catalytic reaction in addition to the intramolecular electron
      transfer in mGDH.

PMID- 19096096
TI  - Functional role of coenzyme Q in the energy coupling of NADH-CoQ oxidoreductase
      (Complex I): stabilization of the semiquinone state with the application of
      inside-positive membrane potential to proteoliposomes.
AB  - Coenzyme Q10 (which is also designated as CoQ10, ubiquinone-10, UQ10, CoQ, UQ or
      simply as Q) plays an important role in energy metabolism. For NADH-Q
      oxidoreductase (complex I), Ohnishi and Salerno proposed a hypothesis that the
      proton pump is operated by the redox-driven conformational change of a Q-binding
      protein, and that the bound form of semiquinone (SQ) serves as its gate [FEBS
      Letters 579 (2005) 45-55]. This was based on the following experimental results:
      (i) EPR signals of the fast-relaxing SQ anion (designated as QNf(.-)) are
      observable only in the presence of the proton electrochemical potential
      (DeltamuH+); (ii) iron-sulfur cluster N2 and QNf(.-) are directly spin-coupled;
      and (iii) their center-to-center distance was calculated as 12angstroms, but
      QNf(.-) is only 5angstroms deeper than N2 perpendicularly to the membrane. After
      the priming reduction of Q to QNf(.-), the proton pump operates only in the steps
      between the semiquinone anion (QNf(.-)) and fully reduced quinone (QH2). Thus, by
      cycling twice for one NADH molecule, the pump transports 4H+ per 2e(-). This
      hypothesis predicts the following phenomena: (a) Coupled with the piericidin A
      sensitive NADH-DBQ or Q1 reductase reaction, DeltamuH+ would be established; (b)
      DeltamuH+ would enhance the SQ EPR signals; and (c) the dissipation of DeltamuH+
      with the addition of an uncoupler would increase the rate of NADH oxidation and
      decrease the SQ signals. We reconstituted bovine heart complex I, which was
      prepared at Yoshikawa's laboratory, into proteoliposomes. Using this system, we
      succeeded in demonstrating that all of these phenomena actually took place. We
      believe that these results strongly support our hypothesis.

PMID- 19096098
TI  - Mitochondrial production of reactive oxygen species: role of complex I and
      quinone analogues.
AB  - Mitochondrial reactive oxygen species (ROS) are mainly produced by the
      respiratory chain enzymes. The sites for ROS production in mitochondrial
      respiratory chain are normally ascribed to the activity of Complex I and III. The
      presence of specific inhibitors modulates reactive oxygen species production in
      Complex I: inhibitors such as rotenone induce a strong ROS increase, while
      inhibitors such as stigmatellin prevent it. We have investigated the effect of
      hydrophilic quinones on Complex I ROS production in presence of different
      inhibitors. Some short chain quinones are Complex I inhibitors (CoQ2, idebenone
      and its derivatives), while CoQ1, decylubiquinone~ (DB) and duroquinone (DQ) are
      good electron acceptors from Complex I. Our results show that the ability of
      short chain quinones to induce an oxidative stress depends on the site of
      interaction with Complex I and on their physical-chemical characteristics. We can
      conclude that hydrophilic quinones may enhance oxidative stress by interaction
      with the electron escape sites on Complex I while more hydrophobic quinones can
      be reduced only at the physiological quinone reducing site without reacting with
      molecular oxygen.

PMID- 19096099
TI  - Effect of CoQ homologues on reactive oxygen generation by mitochondria.
AB  - Effect of CoQ compounds (Qs) on reactive oxygen (ROS) generation by mitochondrial
      complex I was studied using rat liver mitochondria and chemiluminescence probe
      L012. Kinetic analysis revealed that short chain Qs, such as Q2 and idebenone
      enhanced ROS generation by mitochondrial NADH oxidase system by a succinate
      inhibitable mechanism. Lipid peroxidation in mitochondrial membranes induced by
      NADH and iron was inhibited by short chain Qs. The inhibitory activity was
      enhanced by co-oxidation of succinate as determined by chemiluminescence method
      and by electron spin resonance spectroscopy. These results suggested that the
      reduced form of short chain Qs inhibited mitochondrial ROS generation and lipid
      peroxidation.

PMID- 19096100
TI  - Comparison between the free-radical-scavenging activities with vitamin E and
      ubiquinol in biological systems based on their reaction rates: a research
      account.
AB  - Detailed kinetic studies have been performed for the reaction of aroxyl (ArO.)
      radical with vitamin E (alpha-, beta-, gamma-, delta-tocopherol, TocH), ubiquinol
      10, and related antioxidants in micellar solution, using a stopped-flow
      spectrophotometer. The second-order reaction rates (ks) obtained increased in the
      order of hydroquinone < tocol<delta-TocH<ubiquinol-0<gamma-TocH-beta
      TocH<ubiquinol-10<alpha-TocH at pH 4-8. The antioxidants which have lower
      oxidation potentials (Ep) showed higher reactivities. The reaction rates obtained
      in micellar solution were pH dependent because of the dissociation of OH groups
      in the antioxidants. For instance, by comparing the ks values with the mole
      fraction of each molecular form of ubiquinol-10, the reaction rate ks1 (1.21 x
      10(5) M(-1)s(-1)) for undissociated form, ks2 (1.04 x 10(6) M(-1)s(-1)) for
      monoanion and ks3 (0 M(-1)s(-1)) for dianion, and the pKa1 and pKa2 values (11.4
      and 12.7) were determined. It was found that the relative ratio of ks values
      (100:21:20:2.9) of alpha-, beta-, gamma-, delta-tocopherols in micellar
      dispersion has good correlation with the relative biological activities for rat
      fetal resorption, rat haemolysis, and chicken muscle dystrophy. The relative
      antioxidant activities of alpha-tocopherol and ubiquinol-10 have been discussed
      on the basis of the products of the ks values and their concentrations in serum
      and several tissues (heart, muscle, liver, kidney, and brain).

PMID- 19096101
TI  - NADPH-dependent coenzyme Q reductase is the main enzyme responsible for the
      reduction of non-mitochondrial CoQ in cells.
AB  - We purified an NADPH-dependent coenzyme Q reductase (NADPH-CoQ reductase) in rat
      liver cytosol and compared its enzymatic properties with those of the other CoQ10
      reductases such as NADPH: quinone acceptor oxidoreductase 1 (NQO1), lipoamide
      dehydrogenase, thioredoxine reductase and glutathione reductase. NADPH-CoQ
      reductase was the only enzyme that preferred NADPH to NADH as an electron donor
      and was also different from the other CoQ10 reductases in the sensitivities to
      its inhibitors and stimulators. Especially, Zn2+ was the most powerful inhibitor
      for NADPH-CoQ reductase, but CoQ10 reduction by the other CoQ10 reductases could
      not be inhibited by Zn2+. Furthermore, the reduction of the CoQ9 incorporated
      into HeLa cells was also inhibited by Zn2+ in the presence of pyrithione, a zinc
      ionophore. Moreover, NQO1 gene silencing in HeLa cells by transfection of a small
      interfering RNA resulted in lowering of both the NQO1 protein level and the NQO1
      activity by about 75%. However, this transfection did not affect the NADPH-CoQ
      reductase activity and the reduction of CoQ9 incorporated into the cells. These
      results suggest that the NADPH-CoQ reductase located in cytosol may be the main
      enzyme responsible for the reduction of non-mitochondrial CoQ in cells.

PMID- 19096102
TI  - NAD(P)H:quinone oxidoreductase (NQO1) loss of function in Burkitt's lymphoma cell
      lines.
AB  - Two-electron reduction of quinones catalyzed by NAD(P)H:quinone oxidoreductase
      (NQO1) protects cells against oxidative stress and toxic quinones. In fact, low
      level of NQO1 activity is often associated with increased risk of developing
      different types of tumours and with toxic effects linked to environmental
      quinones. In a previous report we analyzed the relationship between the oxidative
      stress induced by UV radiation and CoQ10 content in Burkitt's lymphoma cell lines
      compared to HL-60. The basal content of CoQ10 in Raji cells was slightly higher
      compared to HL-60. Moreover, after irradiation or ubiquinone supplementation in
      the medium, reduced CoQ10 levels were higher in Raji and Daudi cells compared to
      HL-60. In the present work, in order to inquire if NQO1 plays a role in the CoQ
      reducing capacity observed in the lymphoblastoid cell lines, we analyzed the
      transcription and translation products of this gene in Raji and Daudi cells,
      compared to cell lines possessing low and high NQO1 activity. The amount of
      transcripts of this gene in lymphoblastoid cells was comparable to that observed
      in HL-60 cells (low activity), as well as the level of two alternatively spliced
      mRNAs; one of which is described for the first time in this work. From the
      genotype analysis of polymorphisms C609T and C465T we observed that HL-60, Raji
      and Daudi cells were all heterozygous. Furthermore, NQO1 enzyme activity and
      protein synthesis in the cytosol of Raji and Daudi cells were undetectable.
      Therefore in Burkitt's lymphoma cell lines the NQO1 gene is not efficiently
      translated and this effect is not related to (C609T) polymorphism. Further
      studies will be necessary to find the enzyme responsible for CoQ10 reducing
      activity observed in lymphoma cell lines. On the other hand, this result suggests
      a careful re-evaluation of data concerning loss of NQO1 activity and
      polymorphisms in tumour cells.

PMID- 19096103
TI  - Ubichromanol: a prodrug to support mitochondrial ubiquinone functions?
AB  - Ubichromanol-9 (UCa9), with a side chain consisting of nine isoprene units) is a
      reductive cyclization product of ubiquinone-10 (UQ10). It acts as a radical
      scavenging antioxidant and is about half as effective as alpha-tocopherol.
      Already decades ago its one-electron oxidation product, the ubichromanoxyl
      radical had been identified. However, nothing was known so far about the two
      electron oxidation product of this antioxidant and its bioactivity. This study
      proves that ubichromanol can be oxidized to a ubiquinone-like compound with a
      hydroxyl-substituted side chain (UQ10OH), a metabolite that is naturally present
      in bovine liver mitochondria. The bioactivity of this ubiquinone derivative in
      its reduced form as substrate for mitochondrial complex III (cytochrome bc1
      complex) was slightly below that of native ubiquinol, but significantly higher
      than that of reduced alpha-tocopheryl quinone. Since ubiquinone-like molecules
      (UQ10OH, UQ10) were identified as oxidation products of UCa9 during lipid
      peroxidation, this ubiquinone derivative could provide a possibility to combine
      antioxidant properties of chromanols and bioenergetic benefits of UQ10.

PMID- 19096104
TI  - High production of sulfide in coenzyme Q deficient fission yeast.
AB  - We have constructed coenzyme Q deficient fission yeast strains by deletion of ten
      different genes, all of which are absolutely required for the CoQ10 biosynthesis.
      We found that sulfide was highly accumulated in all fission yeast CoQ10 deficient
      mutants. In fission yeast sulfide is required for the synthesis of cysteine and
      homocysteine which are catalyzed by cysteine synthase (Cys1a) and homocysteine
      synthase (Met17), respectively. To better understand the relation between sulfide
      metabolism and coenzyme Q, we expressed cys1a, met17 and hmt2, which encodes
      sulfide-quinone oxidoreductase, in CoQ10 deficient mutants and other mutants, and
      measured the level of sulfide. Although expression of cys1a and met17 lowered
      sulfide production in CoQ10 deficient mutants, hmt2 did not lower the level of
      sulfide, because Hmt2 requires coenzyme Q for its function. In contrast,
      expression of hmt2 lowered sulfide production in cys1a and met17 mutants. These
      and other results indicate that coenzyme Q is important for sulfide oxidation
      through sulfide-quinone oxidoreductase to detoxify excess sulfide in fission
      yeast.

PMID- 19096105
TI  - Stimulation of coenzyme Q synthesis.
AB  - Uptake of dietary coenzyme Q (CoQ) into organs is limited but there are some
      exceptions such as adrenal glands and ovaries. Under deficient conditions an
      optimal solution could be stimulation of the endogenous synthesis. In rodent
      exercise, cold exposure and a few substances elevate the CoQ levels to some
      extent. Investigations of the nuclear receptors PPARalpha, RXRalpha and
      LXRalpha&beta did not answer the question which nuclear receptor regulates CoQ
      biosynthesis and at present we cannot design a ligand for upregulation of the
      synthesis. Upon ultraviolet irradiation of CoQ a number of products are formed
      which influence the synthesis of the mevalonate pathway lipids. Among them
      epoxidated derivatives were identified. Upon chemical epoxidation of a series of
      polyisoprenoids it was found that none of the tested poly-cis polyisoprenols had
      any effect but some of the all-trans polyisoprenols stimulated CoQ synthesis and
      in some cases also inhibited cholesterol biosynthesis. Tocotrienol epoxides were
      proved to be very efficient, those having one epoxide in the side chain doubled
      or trebled the CoQ synthesis while those with two epoxides additionally also
      inhibited cholesterol synthesis by 50-90%. The elevation of CoQ synthesis was
      elicited by increased mRNA levels for biosynthetic enzymes while the inhibition
      point in the cholesterol synthesis was localized to oxidosqualene cyclase.

PMID- 19096107
TI  - Supplemental ubiquinol in patients with advanced congestive heart failure.
AB  - Patients with CHF, NYHA class IV, often fail to achieve adequate plasma CoQ10
      levels on supplemental ubiquinone at dosages up to 900 mg/day. These patients
      often have plasma total CoQ10 levels of less than 2.5 microg/ml and have limited
      clinical improvement. It is postulated that the intestinal edema in these
      critically ill patients may impair CoQ10 absorption. We identified seven patients
      with advanced CHF (mean EF 22%) with sub-therapeutic plasma CoQ10 levels with
      mean level of 1.6 microg/ml on an average dose of 450 mg of ubiquinone daily (150
      600 mg/day). All seven of these patients were changed to an average of 580 mg/day
      of ubiquinol (450-900 mg/day) with follow-up plasma CoQ10 levels, clinical
      status, and EF measurements by echocardiography. Mean plasma CoQ10 levels
      increased from 1.6 microg/ml (0.9-2.0 microg/ml) up to 6.5 microg/ml (2.6-9.3
      microg/ml). Mean EF improved from 22% (10-35%) up to 39% (10-60%) and clinical
      improvement has been remarkable with NYHA class improving from a mean of IV to a
      mean of II (I to III). Ubiquinol has dramatically improved absorption in patients
      with severe heart failure and the improvement in plasma CoQ10 levels is
      correlated with both clinical improvement and improvement in measurement of left
      ventricular function.

PMID- 19096106
TI  - Human CoQ10 deficiencies.
AB  - Coenzyme Q10 (CoQ10 or ubiquinone) is a lipid-soluble component of virtually all
      cell membranes and has multiple metabolic functions. A major function of CoQ10 is
      to transport electrons from complexes I and II to complex III in the respiratory
      chain which resides in the mitochondrial inner membrane. Deficiencies of CoQ10
      (MIM 607426) have been associated with four major clinical phenotypes: 1)
      encephalomyopathy characterized by a triad of recurrent myoglobinuria, brain
      involvement, and ragged-red fibers; 2) infantile multisystemic disease typically
      with prominent nephropathy and encephalopathy; 3) cerebellar ataxia with marked
      cerebellar atrophy; and 4) pure myopathy. Primary CoQ10 deficiencies due to
      mutations in ubiquinone biosynthetic genes (COQ2, PDSS1, PDSS2, and ADCK3
      [CABC1]) have been identified in patients with the infantile multisystemic and
      cerebellar ataxic phenotypes. In contrast, secondary CoQ10 deficiencies, due to
      mutations in genes not directly related to ubiquinone biosynthesis (APTX, ETFDH,
      and BRAF), have been identified in patients with cerebellar ataxia, pure
      myopathy, and cardiofaciocutaneous syndrome. In many patients with CoQ10
      deficiencies, the causative molecular genetic defects remain unknown; therefore,
      it is likely that mutations in additional genes will be identified as causes of
      CoQ10 deficiencies.

PMID- 19096108
TI  - Oxidative stress, endothelial function and coenzyme Q10.
AB  - Reactive oxygen species seem to play an important role in vascular homeostasis.
      In conditions of high oxidative stress, such as chronic heart failure and
      multiple coronary risk factors, the rate of inactivation of nitric oxide to
      peroxynitrite by superoxide anions may be reduced by CoQ10, which can also
      protect against nitrosative damage. CoQ10 may also influence vascular function
      indirectly via inhibition of oxidative damage to LDL. Patients with lower levels
      of extracellular superoxide dismutase (ecSOD) demonstrate greater improvements
      than patients with normal ec-SOD levels, suggesting that the higher the oxidative
      stress the greater the improvement in the endothelium-dependent relaxation after
      the administration of a compound with antioxidant properties like CoQ10. Future
      studies are needed to inquire whether these effects may translate into benefits
      in clinical practice.

PMID- 19096109
TI  - Positive inotropic effect of coenzyme Q10, omega-3 fatty acids and propionyl-L
      carnitine on papillary muscle force-frequency responses of BIO TO-2
      cardiomyopathic Syrian hamsters.
AB  - The inability of heart muscle to generate ventricular pressure to adequately
      propel blood through the cardiovascular system is a primary defect associated
      with congestive heart failure (CHF). Force-frequency relationship (FFR) is one of
      the main cardiac defects associated with congestive heart failure. Thus FFR is a
      convenient methodological tool for evaluating the severity of muscle contractile
      dysfunction and the effectiveness of therapeutic agents. Papillary muscle
      isolated from BIO TO-2 cardiomyopathic Syrian hamsters (CMSHs), show a depressed
      FFR and represents an animal model of human idiopathic dilated cardiomyopathy. In
      the present study we investigated the effect of CoQ10, omega-3 fatty acids,
      propionyl-L-carnitine (PLC) and a combination of these 3 agents (formulation
      HS12607) on FFR in 8 month old BIO TO-2 CMSHs. Papillary muscles isolated from
      the anesthetized animals were placed in an incubation bath and attached to an
      isometric force transducer. A digital computer with an analog/digital interface
      allowed control of both muscle developed force and electrical stimulus
      parameters. Force-frequency response was evaluated, at Lmax, with increasing
      frequencies: 0.06, 0.12, 0.25, 0.5, 1, 2 and 4 Hz. HS12607-treatment produced a
      positive inotropic effect resulting in a significant enhancement (p < 0.05) of
      the peak force at the highest frequencies (1-4 Hz). In the range of frequency of
      1-4 Hz also CoQ10 and omega-3 significantly (p < 0.05) attenuated the fractional
      decline in developed force. The significant improvement (p < 0.05) of the timing
      parameter peak rate of tension rise (+ T') and peak rate of tension fall (-T')
      indicating a faster rate of muscle contraction and relaxation respectively, found
      in CoQ10, omega-3 and PLC-treated CMSHs, may be due to the positive effects of
      these substances on sarcoplasmic reticulum functions. These findings suggest that
      naturally occurring CoQ10, omega-3 and PLC, particularly when administered
      together in a coformulation, might be a valid adjuvant to conventional therapy in
      dilated cardiomyopathy especially when considering that they are natural
      substances, devoid of side effects.

PMID- 19096110
TI  - Coenzyme Q10 (CoQ10) in isolated diastolic heart failure in hypertrophic
      cardiomyopathy (HCM).
AB  - It is well known that by improving mitochondrial bioenergetics, Coenzyme Q10
      improves the systolic function in heart failure. The aim of this study was to see
      whether it benefits the diastolic dysfunction in hypertrophic cardiomyopathy
      (HCM) cases since diastolic relaxation also requires energy like the systole. 200
      mg/day of CoQ10 was added to the conventional treatment in 46 patients with HCM
      diagnosed clinically and by echocardiography and by excluding cases of long
      standing hypertension. A comparable group of 41 age/sex matched cases received
      only conventional therapy. There was a significant improvement in the parameters
      like NYHA class > or = 1, in quality of life (QOL) on 6 minutes walk test, in
      diastolic dysfunction by > or = 1 parameter and in MR > or = 1 grade. Post
      treatment echocardiogram showed significant reduction in left ventricular outflow
      tract (LVOT) gradient > or = 15 mm Hg in obstructive cases (12 out of 46) in the
      treatment group. The mean interventricular septal thickness (IVS) showed a 22.4%
      reduction (p < 0.005). The mean posterior wall thickness showed a 23.1% reduction
      (p < 0.005). No patient in the treatment Group had ventricular tachycardia (VT)
      whereas 4 cases in the control group had VT. In both groups 1 patient was lost
      due to sudden cardiac death (SCD).

PMID- 19096111
TI  - Antiangiogenic and hypolipidemic activity of coenzyme Q10 supplementation to
      breast cancer patients undergoing Tamoxifen therapy.
AB  - Tamoxifen, a non-steroidal anti-estrogen is now widely used and has led to an
      increase in both disease-free and overall survival of women after primary
      surgery. Tamoxifen therapy is found to cause hypertriglyceridemia by reducing
      activity of lipolytic enzymes on triglycerides, and thereby increasing the risk
      of cardiovascular disease. Angiogenesis promotes local tumour progression and
      invasion and enables tumour cell dissemination and metastasis formation. Our
      study has found that co-administration of Coenzyme Q10 (100 mg) along with
      tamoxifen (10 mg, twice a day) to breast cancer patients reduced the level of
      angiogenesis markers and lipid levels.

PMID- 19096112
TI  - Coenzyme Q10 and oxidative imbalance in Down syndrome: biochemical and clinical
      aspects.
AB  - Down syndrome (DS) is a chromosomal abnormality (trisomy 21) associated with
      mental retardation and Alzheimer-like dementia, characteristic change of the
      individual's phenotype and premature ageing. Oxidative stress is known to play a
      major role in this pathology since a gene dose effect leads to elevated ratio of
      superoxide dismutase to catalase/glutathione peroxidase compared to controls in
      all age categories suggesting that oxidative imbalance contributes to the
      clinical manifestation of DS. Hyperuricemia is another feature of DS that has an
      interesting relationship with oxidative stress since uric acid represents an
      important free radical scavenger. However its formation is connected to the
      conversion of Xanthine dehydrogenase (XDH) to Xanthine oxidase (XO) which leads
      to concomitant production of free radicals. Here we report that plasma samples
      from DS patients in pediatric age, despite an increased total antioxidant
      capacity, largely due to elevated Uric acid content (UA), present significantly
      elevated markers of oxidative damage such as increased allantoin levels. Moreover
      DS plasma samples do not differ from healthy control ones in terms of Coenzyme
      Q10 and susceptibility to peroxidative stimuli. On the contrary, lymphocyte and
      platelet CoQ10 content was significantly lower in DS patients, a fact that might
      underlie oxidative imbalance at a cellular level.

PMID- 19096113
TI  - Diet supplement CoQ10 delays brain atrophy in aged transgenic mice with mutations
      in the amyloid precursor protein: an in vivo volume MRI study.
AB  - We tested the hypotheses that supplemental intake of the diet supplement Coenzyme
      Q10 (CoQ10) could delay brain atrophy in double transgenic amyloid precursor
      protein (APP) / presenilin 1 (PS1), single transgenic APP and PS1 as well as wild
      type mice by volume MR image in vivo. One hundred and twelve mice (28 APP/PS1, 28
      APP, 28 PS1 and 28 wild types) were studied. Half of each genotype group (n = 14
      per group) was treated with CoQ10 2400 mg/kg/day, and the other half with placebo
      for 60 days. Magnetic resonance (MR) images were used to obtain the volumes of
      the hemispheres and hippocampi. APP / PS1, APP, PS1 and wild type mice treated
      with CoQ10 exhibited significantly less atrophy in hemisphere and hippocampus
      than those receiving placebo. The neuro-protective effect of the CoQ10 on
      hemispheric volume, and hippocampal volume was related to genotype; greater in
      APP/PS1 than APP and PS1 mice and less in wild type mice. Our result indicated
      that CoQ10 may have therapeutic potential in the prevention and treatment of MCI
      and AD.

PMID- 19096114
TI  - Functions of coenzyme Q10 in inflammation and gene expression.
AB  - Clinical studies demonstrated the efficacy of Coenzyme Q10 (CoQ10) as an adjuvant
      therapeutic in cardiovascular diseases, mitochondrial myopathies and
      neurodegenerative diseases. More recently, expression profiling revealed that
      Coenzyme Q10 (CoQ10) influences the expression of several hundred genes. To
      unravel the functional connections of these genes, we performed a text mining
      approach using the Genomatix BiblioSphere. We identified signalling pathways of G
      protein coupled receptors, JAK/STAT, and Integrin which contain a number of CoQ10
      sensitive genes. Further analysis suggested that IL5, thrombin, vitronectin,
      vitronectin receptor, and C-reactive protein are regulated by CoQ10 via the
      transcription factor NFkappaB1. To test this hypothesis, we studied the effect of
      CoQ10 on the NFkappaB1-dependent pro-inflammatory cytokine TNF-alpha. As a model,
      we utilized the murine macrophage cell lines RAW264.7 transfected with human
      apolipoprotein E3 (apoE3, control) or pro-inflammatory apoE4. In the presence of
      2.5 microM or 75 microM CoQ10 the LPS-induced TNF-alpha response was
      significantly reduced to 73.3 +/- 2.8% and 74.7 +/- 8.9% in apoE3 or apoE4 cells,
      respectively. Therefore, the in silico analysis as well as the cell culture
      experiments suggested that CoQ10 exerts anti-inflammatory properties via
      NFkappaB1-dependent gene expression.

PMID- 19096115
TI  - Coenzyme Q10 levels in women with preeclampsia living at different altitudes.
AB  - BACKGROUND: Preeclampsia is a common disorder of pregnancy exhibiting abnormal
      plasma and placental coenzyme Q10 (CoQ10) levels when compared to normal
      pregnancies. OBJECTIVE: To evaluate CoQ10 levels both in plasma and placenta
      among normal pregnant (n = 60) and preeclamptic (n = 63) primigravid women and
      determine the effect of high or low altitude residency. STUDY DESIGN: CoQ10 was
      determined using High Performance Liquid Chromatography (HPLC) technique and
      group comparisons were performed. RESULTS: Preeclamptic women living at high
      altitude displayed significantly lower CoQ10 plasma levels (0.64 +/- 0.23 vs.
      0.82 +/- 0.46 micromol/L, p = 0.05). No differences were found in CoQ10 plasma
      levels among women living at sea level. Interestingly, plasma CoQ10 levels at low
      altitude in normal pregnancies were significantly lower than high altitude normal
      pregnancies. Compared to normal pregnancies, preeclamptic women displayed higher
      placental CoQ10 content, which was only significant among those living at sea
      level (0.120 +/- 0.07 vs. 0.076 +/- 0.04 ng/mg protein, p < 0.005). Normal
      pregnant women living at high altitude displayed higher placental CoQ10 content
      when compared to those residing at sea level (p < 0.0005). CONCLUSION: Women
      suffering from preeclampsia (high or low altitude) display high placental CoQ10
      content, with significant low plasma CoQ10 levels among those residing in high
      altitude. More research is warranted to establish the cause-effect relationship
      between CoQ10 levels and preeclampsia.

PMID- 19096116
TI  - Plasma and thrombocyte levels of coenzyme Q10 in children with Smith-Lemli-Opitz
      syndrome (SLOS) and the influence of HMG-CoA reductase inhibitors.
AB  - INTRODUCTION: SLOS is caused by a defect of cholesterol synthesis. HMG-CoA
      reductase inhibitors have been shown to improve biochemical parameters in this
      condition, but they have also been associated with CoQ10 deficiency in patients
      with hypercholesterolemia. The aim of this study was to analyse plasma and
      intracellular CoQ10 levels in SLOS patients and to determine the influence of HMG
      CoA reductase inhibitors. METHODS: Plasma concentrations of CoQ10 and vitamin E
      were measured in 14 patients, intracellular CoQ10 levels were determined in
      platelets of 10 patients with SLOS and compared to controls. RESULTS: Plasma
      CoQ10 and vitamin E levels were significantly lower in SLOS patients. This
      difference equalised after adjustment to cholesterol concentrations. Treatment
      with simvastatin did not influence CoQ10 levels and redox status. Platelet CoQ10
      concentrations were similar between patients and controls but there were striking
      differences in the CoQ10 redox status with a decrease of oxidised CoQ10.
      CONCLUSION: Decreased concentrations of plasma CoQ10 and vitamin E in SLOS
      patients are due to a diminished carrier capacity. The higher percentage of
      reduced CoQ10 in platelets points to an up-regulation of mitochondrial protection
      mechanisms. Further studies are needed to evaluate a possible benefit of CoQ10
      supplementation in SLOS patients.

PMID- 19096117
TI  - Safety assessment of coenzyme Q10 (CoQ10).
AB  - Coenzyme Q10 (CoQ10) is a naturally occurring component present in living cells.
      Its physiological function is to act as an essential cofactor for ATP production,
      and to perform important antioxidant activities in the body. In most countries,
      CoQ10 has been widely used as a dietary supplement for more than 20 years.
      Recently, the use of CoQ10 as a dietary supplement has grown with a corresponding
      increase in daily dosage. The present review describes the safety profile of
      CoQ10 on the basis of animal and human data. The published reports concerning
      safety studies indicate that CoQ10 has low toxicity and does not induce serious
      adverse effects in humans. The acceptable daily intake (ADI) is 12mg/kg/day,
      calculated from the no-observed-adverse-effect level (NOAEL) of 1200 mg/kg/day
      derived from a 52-week chronic toxicity study in rats, i.e., 720 mg/day for a
      person weighing 60 kg. Risk assessment for CoQ10 based on various clinical trial
      data indicates that the observed safety level (OSL) for CoQ10 is 1200
      mg/day/person. Evidence from pharmacokinetic studies suggest that exogenous CoQ10
      does not influence the biosynthesis of endogenous CoQ9/CoQ10 nor does it
      accumulate into plasma or tissues after cessation of supplementation. Overall,
      these data from preclinical and clinical studies indicate that CoQ10 is highly
      safe for use as a dietary supplement. Additionally, analysis of CoQ10
      bioavailability or its pharmacokinetics provides the pertinent safety evaluation
      for CoQ10.

PMID- 19096118
TI  - Blood CoQ10 levels and safety profile after single-dose or chronic administration
      of PureSorb-Q40: animal and human studies.
AB  - Coenzyme Q10 (CoQ10) is known to be highly hydrophobic and, as such, insoluble in
      water: this leads to serious inconvenience when trying to incorporate it in food
      products. Its absorption is also known to be very limited. PureSorb-Q40 (P40)
      (Water-soluble type CoQ10 powder, CoQ10 content 40 w/w % was developed in order
      to improve its use with food products and to enhance its absorption. In the
      present study the absorption of this novel formulation was compared to a
      conventional lipid soluble CoQ10 by administering both products to rats and
      humans. Acute, single-administration studies in rats showed that P40 has a higher
      absorption, compared to lipid soluble CoQ10, both in prandial and fasting states.
      Similarly, single administration in humans revealed a higher absorption level for
      P40, taken in the fasting state or together with meals. In the rat study, no
      adverse effects were observed with P40 at doses up to 2,000 mg/kg in both sexes.
      In a double-blind, placebo controlled, comparative study conducted on 46 healthy
      volunteers and randomly divided into two groups, in the group receiving 900~mg of
      CoQ10 per day, for 4 consecutive weeks, the average level at two weeks was 8.79
      +/- 3.34 microg/mL, similar to the corresponding level after 4 weeks (8.33 +/-
      4.04 microg/mL). After 2 weeks of washout, serum CoQ10 level decreased to 1.30 +/
      0.49 microg/mL. P40 intake did not cause any significant changes in symptoms and
      clinical laboratory tests as assessed by physical, hematological, blood
      biochemical or urinalysis. Clinical examinations also did not reveal any
      abnormalities. The above blood (serum) CoQ10 level at 2 weeks after start of
      intake was compared with other reported values. The same dose of CoQ10
      (900mg/day), when administered by softgel capsules yielded a plasma CoQ10
      concentration of 3.6 microg/mL, while P40 levels were 8.79 +/- 3.34 microg/mL.
      These levels are remarkably high for instance when compared to the corresponding
      levels obtained, in patients affected by Parkinson's disease, with CoQ10 doses up
      to 2,400mg/day. A clinical study was conducted using doses of 300 mg/day and 600
      mg/day, in patients affected by cardiovascular disease. Also in this case there
      was linearity in the response with the levels obtained by administering P40 at a
      dose of 100 and 900 mg/day.

PMID- 19096119
TI  - Supplementation with CoQ10 lowers age-related (ar) NOX levels in healthy
      subjects.
AB  - Our work has identified an aging-related ECTO-NOX activity (arNOX), a
      hydroquinone oxidase which is cell surface located and generates superoxide. This
      activity increases with increasing age beginning >30 y. Because of its cell
      surface location and ability to generate superoxide, the arNOX proteins may serve
      to propagate an aging cascade both to adjacent cells and to oxidize circulating
      lipoproteins as significant factors determining atherogenic risk. The generation
      of superoxide by arNOX proteins is inhibited by Coenzyme Q10 as one basis for an
      anti-aging benefit of CoQ10 supplementation in human subjects. In a preliminary
      pilot study, 25 female subjects between 45 and 55 y of age were recruited at
      Stanford University from the Palo Alto, CA area. Informed consent was obtained.
      Ten of the subjects received Coenzyme Q10 supplementation of 180 (3 x 60 mg) per
      day for 28 days. Serum, saliva and perspiration levels of arNOX were determined
      at 7, 14 and 28 days of CoQ10 supplementation and compared to the initial
      baseline value. Activity correlated with subject age up to a maximum between age
      50 and 55 years of age for saliva and perspiration as well and then declined.
      With all three sources, the arNOX activity extrapolated to zero at about age 30.
      Response to Coenzyme Q10 also increased with age being least between ages 45 and
      50 and greatest between ages 60 and 65. With all three biofluids, arNOX activity
      was reduced between 25 and 30% by a 3 x 60 mg daily dose Coenzyme Q10
      supplementation. Inhibition was the result of Coenzyme Q10 presence.

PMID- 19096120
TI  - arNOX activity of saliva as a non-invasive measure of coenzyme Q10 response in
      human trials.
AB  - arNOX is a coenzyme Q10-inhibited, aging-related ECTO-NOX protein of the cell
      surface also present in sera. It is capable of superoxide generation measured as
      superoxide dismutase-inhibited reduction of ferricytochrome c and is a potential
      contributor to atherogenic risk. Here, we report an arNOX activity of saliva of
      older individuals also inhibited by coenzyme Q10. The activity first appears
      after age 30 to a near maximum at about age 55. Those surviving beyond age 55
      usually have reduced arNOX activities. Our studies demonstrate significant (25 to
      30%) reduction of arNOX levels with coenzyme Q10 supplementation of 60 mg (2 x 30
      mg) per day for 28 days. Activity correlated with age. Response to coenzyme Q10
      increased with age being greatest between ages 60 and 65. Saliva arNOX levels
      varied in a regular pattern throughout the day so it was important that samples
      be collected at approximately the same time each day for comparative purposes.
      The coenzyme Q10 response was reversible and within 12 h after the last intake of
      coenzyme Q10, the salivary arNOX levels returned to base line. The findings
      suggest that salivary arNOX provides a convenient and non-invasive method to
      monitor arNOX levels in clinical coenzyme Q10 intervention trials with the
      response levels paralleling those seen with serum and cellular arNOX.

PMID- 19096121
TI  - Mechanisms of inhibitory effects of CoQ10 on UVB-induced wrinkle formation in
      vitro and in vivo.
AB  - Photodamaged skin exhibits wrinkles, pigmented spots, dryness and tumors. Solar
      UV radiation induces cyclobutane pyrimidine dimers (CPD) and further produces
      base oxidation by reactive oxygen species (ROS). ROS are thought to be a major
      factor to initiate the up-regulation of matrix metalloproteinases (MMPs) in
      keratinocytes and fibroblasts via activation of receptor proteins on the cell
      membrane of keratinocytes and fibroblasts, and to degrade fiber components in
      dermis, leading to wrinkle formation. Coenzyme Q10 (CoQ10) was reported to reduce
      ROS production and DNA damage triggered by UVA irradiation in human keratinocytes
      in vitro. Further, CoQ10 was shown to reduce UVA-induced MMPs in cultured human
      dermal fibroblasts. We speculated that UVB radiation-induced cytokine production
      in keratinocytes may be inhibited by CoQ10, resulting in the reduction of MMPs in
      fibroblasts leading to wrinkle reduction. Our in vitro studies showed that UVB
      induced IL-6 production of normal human keratinocyte (NHKC) decreased in the
      presence of CoQ10. Furthermore, MMP-1 production of fibroblasts cultured with the
      medium containing CoQ10 collected from UVB-irradiated NHKC significantly
      decreased during 24 h culture. In the clinical trial study, we found that the use
      of 1% CoQ10 cream for five months reduced wrinkle score grade observed by a
      dermatologist. Taken together, our results indicate that CoQ10 may inhibit the
      production of IL-6 which stimulate fibroblasts in dermis by paracrine manner to
      up-regulate MMPs production, and contribute to protecting dermal fiber components
      from degradation, leading to rejuvenation of wrinkled skin.

PMID- 19096122
TI  - Aging skin is functionally anaerobic: importance of coenzyme Q10 for anti aging
      skin care.
AB  - The functional loss of mitochondria represents an inherent part in modern
      theories trying to explain the cutaneous aging process. The present study shows
      significant age-dependent differences in mitochondrial function of keratinocytes
      isolated from skin biopsies of young and old donors. Our data let us postulate
      that energy metabolism shifts to a predominantly non-mitochondrial pathway and is
      therefore functionally anaerobic with advancing age. CoQ10 positively influences
      the age-affected cellular metabolism and enables to combat signs of aging
      starting at the cellular level. As a consequence topical application of CoQ10 is
      beneficial for human skin as it rapidly improves mitochondrial function in skin
      in vivo.

PMID- 19096123
TI  - Improved HPLC column-switching determination of Coenzyme Q and Vitamin E in
      plasma.
AB  - A novel isocratic modified column-switching HPLC method for automated
      quantitative analysis of Vitamin E and Coenzyme Q, in the reduced and oxidized
      form, is described. Many column-switching HPLC methods are found in the
      literature, also for determining antioxidant substances, but we developed a
      different system of column-switching. An empty column, 5 cm long, was connected
      to the switching valve, before the sample loop and the extraction column. The
      sample loop was connected directly after the empty column. The inserted column,
      containing about 1.4 ml of the extraction eluent simulated a gradient elution,
      enhancing sensitivity and resolution. When switching the columns, the empty
      column is placed right before the extraction column and acts as a static mixer
      for the extraction phase and the incoming analytical phase. Samples were cleaned
      from interfering compounds by transfer onto a extraction-column, using a C-8
      silica. Separation was performed onto an analytical column C18 3 m icrom, 150 mm
      x 4.6 mm at a flow rate of 1.0 ml/min with 20 mmol/l lithium
      perchlorate/perchloric acid, pH3.0 in Ethanol as analytical eluent. Detection was
      performed with a ESA Coulochem 5100 A model. The method was found to be suitable
      for automated analysis of Coenzyme Q, reduced and oxidized form, and Vitamin E in
      serum.

PMID- 19096124
TI  - Oxidative stress status in liver mitochondria and lymphocyte DNA damage of
      atherosclerotic rabbits supplemented with water soluble coenzyme Q10.
AB  - The effects of the administration of water soluble coenzyme Q10 (25 mg/kg per
      day) over 30 days, after 50 days feeding on a high-fat diet (3% lard + 1.3%
      cholesterol), were investigated in the plasma and liver mitochondria of rabbits.
      Results showed that this atherogenic diet enhanced lipid levels both in plasma
      and liver mitochondria, reduced plasma and mitochondrial concentrations of
      retinol and coenzyme Q10, led to higher DNA damage in peripheral blood
      lymphocytes and reactive oxygen species concentration in liver mitochondria. The
      treatment of animals with coenzyme Q10 reduced (to the healthy group levels)
      lipid concentration in liver mitochondria with no effect on plasma lipids,
      increased mitochondrial levels of alpha-tocopherol, restored mitochondrial
      coenzyme Q10 and improved alpha-tocopherol levels in plasma. Moreover, coenzyme
      Q10 supplementation reduced mitochondrial reactive oxygen species levels and
      decreased DNA damage in peripheral blood lymphocytes. The findings suggest that
      antioxidant therapy with coenzyme Q10 may be used in the treatment of liver
      pathologies associated to the intake of high-fat, atherogenic, diets.

PMID- 19096125
TI  - Mitochondrial transcription factors TFA, TFB1 and TFB2: a search for DNA
      variants/haplotypes and the risk of cardiac hypertrophy.
AB  - Mitochondrial transcription factors mtTFA, mtTFB1 and mtTFB2 are required for the
      replication of mitochondrial DNA (mtDNA), regulating the number of mtDNA copies.
      Mice with a mtTFA deletion showed a reduced number of mtDNA copies, a reduction
      in respiratory chain activity, and a characteristic dilated cardiomyopathy. DNA
      variants in these genes could be involved in the risk for cardiac hypertrophy
      (HCM). We determined the variation in the TFAM, TFB1M, and TFB2M genes (using
      SSCA, DHPLC, and direct sequencing) in a total of 200 HCM-patients from Spain and
      Germany, and in 250 healthy controls. We found several common polymorphisms that
      defined haplotype blocks in these genes, with frequencies that did not differ
      between patients and controls. We also found four novel variants in patients
      which were absent in the controls: -91 C > A (5'-UTR) and Ala105 > Thr in TFAM,
      and Thr211 > Ala and Arg256 > Lys in TFB1M. The three missense changes were in
      highly conserved amino acids, and could be involved in HCM-risk. In conclusion,
      common variants in the mitochondrial transcription factors were not associated
      with the risk for HCM. However, rare DNA variants (putative mutations) could be
      involved in the pathogenesis of HCM in a reduced number of cases.

PMID- 19096126
TI  - Expression of hypoxia-inducible factor (HIF)-1alpha and vascular endothelial
      growth factor (VEGF)-D as outcome predictors in resected esophageal squamous cell
      carcinoma.
AB  - Hypoxia-inducible factor (HIF)-1alpha and vascular endothelial growth factor
      (VEGF) are important angiogenic factors in human cancers. Relative to VEGF-C,
      prognostic significance of VEGF-D expression and its association with HIF-1alpha
      expression remain elusive in esophageal squamous cell cancer (ESCC). We studied
      expression of HIF-1alpha and VEGF-D using immunohistochemistry in 85 resected
      ESCC specimens and correlated results with patients' clinicopathologic parameters
      and survival. Association between expression of HIF-1alpha and VEGF-D was
      investigated using a concordance analysis. High expression of HIF-1alpha and VEGF
      D was observed in 52 (61.2%) and 56 (65.9%) patients, respectively. HIF-1alpha
      expression correlated well with tumor stage (P = 0.041), whereas VEGF-D
      expression correlated with tumor stage (P = 0.027) and N status (P = 0.019).
      Groups of high HIF-1alpha and VEGF-D showed worse survivals than those of low
      expression (P = 0.002 and 0.001, respectively). Multivariate analysis supported
      expression of HIF-1alpha and VEGF-D as significant survival predictors (P = 0.044
      and 0.035, respectively). A concordance rate of 69.5% was observed between
      expression of HIF-1alpha and VEGF-D. In conclusion, protein expression of HIF
      1alpha and VEGF-D are independent prognostic predictors. An association between
      expression of HIF-1alpha and VEGF-D suggests that these two angiogenic factors
      are essential in progression of ESCC.

PMID- 19096127
TI  - The impact of folate pathway polymorphisms combined to nutritional deficiency as
      a maternal predisposition factor for Down syndrome.
AB  - Polymorphisms in genes encoding folate metabolizing enzymes have been linked to
      an increased risk of maternal chromosomal nondisjunction in several populations.
      With the purpose of evaluating this relationship, we compared the frequencies of
      677C>T and 1298A>C polymorphisms in the methylenetetrahydrofolate reductase gene
      (MTHFR) and 66A>G in the methionine synthase reductase gene (MTRR) between 103
      young mothers of Down syndrome (DS) individuals and 108 control mothers, whose
      offspring was karyotypically normal, correlating it with an estimative of folate
      and - related micronutrients levels intake. Maternal and paternal transmission
      frequencies of MTHFR 677T allele were also examined to access potential parent-of
      origin effects. PCR-RFLP for genomic DNA was accomplished and allele/genotype
      frequencies differences were determined using the x(2) test, whereas pattern of
      transmission of the MTHFR 677 allele was analyzed by transmission disequilibrium
      test. None of the polymorphisms seemed to be more frequent in case mothers than
      in controls, either individually or combined. The estimative of nutritional
      intake revealed that folate consumption median was inadequate in both groups,
      whereas methionine and zinc consumption medians were significantly greater in
      control mothers. It suggests that such interaction between genetic profile and
      environment could predispose this sub group of women to have a DS child.
      Additional studies focusing the interaction between nutritional intakes,
      biochemical data and folate pathway polymorphisms are needed to confirm the
      present results. The possibility of neutralize the biochemical negative effects
      of folate-related polymorphisms through oral supplementation could provide new
      targets for DS prevention.

PMID- 19096128
TI  - Circulating cell-free DNA in plasma of locally advanced rectal cancer patients
      undergoing preoperative chemoradiation: a potential diagnostic tool for therapy
      monitoring.
AB  - Circulating cell-free DNA opens up an interesting field for therapy monitoring,
      in particular during multimodal therapy protocols. The objective of this proof of
      principle study was to evaluate whether the amount of circulating plasma DNA has
      the potential to serve as a marker for therapy monitoring during the treatment
      course of locally advanced rectal cancer patients. We especially focused on
      kinetics of circulating DNA to assess whether variances in kinetics have the
      potential to discriminate between therapy responders and nonresponders. The
      amount of circulating DNA in plasma of rectal cancer patients undergoing
      preoperative chemoradiation was determined using real-time PCR before
      chemoradiation, after the end of chemoradiation and at the end of treatment. The
      study population was divided into responders (ypT0-T2 stage) and nonresponders
      (ypT3-T4 stage). Both groups showed comparable median plasma DNA values before
      and after the end of chemoradiation. At the end of treatment responders showed a
      further decrease in circulating DNA, whereas in nonresponders the circulating DNA
      manifestly increased (P = 0.006). This study demonstrates that circulating DNA in
      plasma of rectal cancer patients undergoing preoperative chemoradiation might
      serve as a surrogate marker to discriminate between responders and nonresponders.
      Therefore, we hypothesize that quantification of plasma DNA could be of use as an
      easily accessible tool for therapy monitoring in these patients.

PMID- 19096129
TI  - Sialic acid and sialidase activity in acute stroke.
AB  - Stroke is a heterogeneous syndrome caused by multiple disease mechanisms,
      resulting in a disruption of cerebral blood flow with subsequent tissue damage.
      It is well known that erythrocytes have a large amount of sialic acid and could
      represent a model to investigate changes occurring in a pathology like stroke.
      The aim of this study was to investigate a possible relationship among
      erythrocyte membrane, plasma and sialic acid content. The possible impact of the
      sialic acid content and the activity of sialidase on stroke severity was also
      evaluated. The study population consisted of 54 patients with a first stroke and
      of 53 age-and sex matched healthy volunteers. The total bound sialic acid was
      substantially decreased in patients. There was a significant correlation between
      the sialidase activity values and the severity of the neurological deficit
      defined by the National Institute of Health Stroke Scale. This study shows that
      low sialic acid erythrocyte concentrations with contemporary high sialic acid
      plasma levels and elevated sialidase activity can be considered as markers of
      ischemic stroke. Further investigations are needed to clarify the possible role
      of these biochemical changes in producing and sustaining cerebral ischemic
      damage.

PMID- 19096130
TI  - Microsatellite scan identifies new candidate genes for susceptibility to
      alcoholic chronic pancreatitis in Japanese patients.
AB  - Alcohol abuse is one of the most common risk factor for chronic pancreatitis, but
      the underlying pathophysiological mechanisms remain unclear. The aim of this
      study was to identify genes that contribute to susceptibility or resistance for
      alcoholic chronic pancreatitis by screening the whole genome. Sixty-five patients
      with alcoholic chronic pancreatitis (63 men and 2 women, mean age 55.2 years) and
      99 healthy Japanese controls were enrolled in this study. This was an association
      study using 400 polymorphic microsatellite markers with an average spacing of
      10.8 cM distributed throughout the whole genome. This search revealed 10
      candidate susceptibility regions and 5 candidate resistant regions throughout the
      genome. No specific microsatellite markers were detected in association with
      previously reported susceptibility genes for chronic pancreatitis, such as PRSS1,
      PRSS2, CTRC, SPINK1, CFTR, ALDH2, and CYP2E1. Among the statistically significant
      markers, D15S1007 on chromosome 15q14 showed strong evidence for disease
      susceptibility (70.8% vs. 35.1%, Pc = 0.0001). Within 500 kb of D15S1007, several
      genes were candidate genes for susceptibility, including FMN1, DKFZP686C2281,
      LOC440268, RYR3, and AVEN, This study identified 10 candidate susceptibility and
      5 candidate resistant regions that may contain genes involved in ACP
      pathogenesis.

PMID- 19096131
TI  - Biological signatures of brain damage associated with high serum ferritin levels
      in patients with acute ischemic stroke and thrombolytic treatment.
AB  - BACKGROUND AND PURPOSE: Increased body iron stores have been related to greater
      oxidative stress and brain injury in clinical and experimental cerebral ischemia
      and reperfusion. We aimed to investigate the biological signatures of
      excitotoxicity, inflammation and blood brain barrier disruption potentially
      associated with high serum ferritin levels-related damage in acute stroke
      patients treated with i.v. t-PA. METHODS: Serum levels of ferritin (as index of
      increased cellular iron stores), glutamate, interleukin-6, matrix
      metalloproteinase-9 and cellular fibronectin were determined in 134 patients
      treated with i.v. t-PA within 3 hours from stroke onset in blood samples obtained
      before t-PA treatment, at 24 and 72 hours. RESULTS: Serum ferritin levels before
      t-PA infusion correlated to glutamate (r = 0.59, p < 0.001) and interleukin-6 (r
      = 0.55, p < 0.001) levels at baseline, and with glutamate (r = 0.57, p < 0.001),
      interleukin-6 (r = 0.49, p < 0.001), metalloproteinase-9 (r = 0.23, p = 0.007)
      and cellular fibronectin (r = 0.27, p = 0.002) levels measured at 24 hours and
      glutamate (r = 0.415, p < 0.001), interleukin-6 (r = 0.359, p < 0.001) and
      metalloproteinase-9 (r = 0.261, p = 0.004) at 72 hours. The association between
      ferritin and glutamate levels remained after adjustment for confounding factors
      in generalized linear models. CONCLUSIONS: Brain damage associated with increased
      iron stores in acute ischemic stroke patients treated with iv. tPA may be
      mediated by mechanisms linked to excitotoxic damage. The role of inflammation,
      blood brain barrier disruption and oxidative stress in this condition needs
      further research.

PMID- 19096132
TI  - Dopaminergic neurons derived from BG01V2, a variant of human embryonic stem cell
      line BG01.
AB  - BACKGROUND AND PURPOSE: Human embryonic stem cells (hESC) are considered a
      renewable source of dopamine producing neurons, and are of particular interest
      for their potential clinical use in Parkinson's disease. In this study, we
      characterized human dopaminergic neurons generated by stromal-derived inducing
      activity (SDIA) from BG01V2, a strain of human embryonic stem cell line, BG01,
      characterized by a chromosome 17 trisomy. Similar chromosomal changes have been
      repeatedly observed in hESC cultures in different laboratories, indicating the
      importance of chromosome 17 for growth and adaptation of hESC to culture.
      METHODS: We investigated in vitro proliferation of differentiating cells using a
      BrDU incorporation assay, and monitored the cell population in long term
      cultures. Despite the cytogenetic abnormality, TH+ neurons were postmitotic at
      all stages of differentiation. After 30 days of differentiation, cell division
      ceased in 91% of the overall population of cells in the culture, indicating
      intact cell cycle regulation. RESULTS: Expression of midbrain specific marker
      genes (Otx2, Pax5, Msx-1) showed differentiation of hESC-derived neural
      progenitor cells into midbrain specific dopamine neurons. These neurons expressed
      the dopamine transporter (DAT), and displayed functional DAT activity and
      electrical excitability. CONCLUSIONS: TH+ cells derived from the BG01V2 hESC line
      using SDIA are postmitotic and have functional characteristics of normal
      dopaminergic neurons.

PMID- 19096133
TI  - A genetic fusion GDNF-C fragment of tetanus toxin prolongs survival in a
      symptomatic mouse ALS model.
AB  - PURPOSE: Amyotrophic Lateral Sclerosis (ALS) is a paralyzing disorder that kills
      individuals within three to five years of onset without any possibility for
      effective treatment. One proposed therapy has been the use of neurotrophic
      factors to inhibit the apoptosis of motorneurones. At the present, one way to
      deliver neurotrophic factors after intramuscular injection to the motor neurones
      is through the use of adenoviral vectors. An alternative strategy is the use of
      the atoxic C fragment of tetanus toxin (TTC) as a neurotrophic factor carrier for
      motorneurones. METHODS: We have produced the recombinant protein fusion Glial
      Derived Neurotrophic Factor and C fragment of tetanus toxin (GDNF-TTC) and we
      have tested its antiapoptotic activity in degeneration culture cells and in the
      symptomatic SOD;{G93A} transgenic animal model for ALS. RESULTS: We demonstrated
      that GDNF-TTC induces the neuronal survival Akt kinase pathway in mouse cortical
      culture neurons and~maintains its antiapoptotic neuronal activity in Neuro2A
      cells. Moreover, we have found that genetic fusion is able to increase survival
      by 9 days and improves life quality in symptomatic ALS animal models. CONCLUSION:
      These results suggest that recombinant GDNF-TTC fusion protein intramuscular
      injections provide a potential therapy for ALS treatment.

PMID- 19096134
TI  - Protective effects of gastrodia elata on aluminium-chloride-induced learning
      impairments and alterations of amino acid neurotransmitter release in adult rats.
AB  - PURPOSE: High brain levels of aluminum (Al) can be neurotoxic and cause learning
      and memory deficits. Gastrodia elata (GE) is a Chinese herb widely used for
      improving mental function in traditional Chinese medicine. We measured changes in
      Al-induced neurotransmitter alteration and performance on a learning and memory
      task to elucidate the mechanism of Al toxicity and to assess whether these
      alterations could be attenuated by GE. METHODS: Thirty-six adult, male rats were
      randomly divided into six groups. Four Al-exposed groups were given aluminum
      chloride at 5 mg/kg/day or 10 mg/kg/day (i.p.) for two months, with two of these
      groups (one for each dose of Al) receiving GE (0.4 g/kg, via oral intubation,
      with the GE powder mixed in the drinking water) while the other two groups
      received vehicle. A GE control group was given injections of saline plus GE and a
      saline control group was given injections of saline and with 3 injection days and
      one day off. A step-down test was used to measure learning and memory ability. Al
      concentrations in the neocortex were assayed with a graphite furnace atomic
      absorption spectrophotometer. Amino acid neurotransmitter levels in the neocortex
      were determined by high performance liquid chromatogram-fluorescence. RESULTS: Al
      exposed rats showed impaired learning and memory ability as indicated by shorter
      step down latency and more retention errors. Cortical concentrations (mean +/-
      SEM) of Al were: 56.22 +/- 34.10 ng/g (wet weight) in the Saline control group;
      172.87 +/- 111.06 in the 5 mg/kg/dayAl group; 289.15 +/- 102.55 in the 10 mg Al
      group; 74.98 +/- 19.00 in the GE control group; 232.55 +/- 35.74 in 5 mg Al+GE
      group; and 291.35 98.38 in 10 mg Al+GE group respectively. Al exposure produced a
      significant increase in cortical GABA levels. Gastrodia elata reduced learning
      and memory deficits without affecting brain Al levels. CONCLUSIONS: Rats exposed
      to AlCl_{3} suffer from deficits in learning and memory, accompanied by increases
      in GABA levels in the neocortex. Gastrodia elata is effective in improving memory
      functions and normalizing GABA levels.

PMID- 19096135
TI  - Cerebellar control of cortico-striatal LTD.
AB  - PURPOSE: Recent anatomical studies showed the presence of cerebellar and basal
      ganglia connections. It is thus conceivable that the cerebellum may influence the
      striatal synaptic transmission in general, and synaptic plasticity in particular.
      METHODS: In the present neurophysiological investigation in brain slices, we
      studied striatal long-term depression (LTD), a crucial form of synaptic
      plasticity involved in motor learning after cerebellar lesions in rats. RESULTS:
      Striatal LTD was fully abolished in the left striatum of rats with right
      hemicerebellectomy recorded 3 and 7 days following surgery, when the motor
      deficits were at their peak. Fifteen days after the hemicerebellectomy, rats had
      partially compensated their motor deficits and high-frequency stimulation of
      excitatory synapses in the left striatum was able to induce a stable LTD.
      Striatal plasticity was conversely normal ipsilaterally to cerebellar lesions, as
      well as in the right and left striatum of sham-operated animals. CONCLUSIONS:
      These data show that the cerebellum controls striatal synaptic plasticity,
      supporting the notion that the two structures operate in conjunction during motor
      learning.

PMID- 19096136
TI  - Neural correlates of recovery from acute hemispatial neglect.
AB  - PURPOSE: To investigate the neural correlates associated with recovery from acute
      spatial neglect resulting from right hemispheric stroke. METHODS: Four neglect
      patients were investigated both behaviourally and by fMRI at an acute (18 +/- 5
      days) and at a chronic stage (123 +/- 18 days) post stroke. RESULTS: At the
      second assessment all patients showed substantial behavioural improvements. These
      were associated with an increase of neural activity in the right middle frontal
      gyrus, right inferior parietal cortex, right inferior temporal gyrus/fusiform
      gyrus, left superior temporal gyrus/angular gyrus and left anterior cingulate
      gyrus. Decreased neural activity at the second assessment was found in the right
      parahippocampal gyrus and left fusiform gyrus. CONCLUSIONS: The pattern of neural
      reorganisation comprises areas of a right hemisphere fronto-parietal attentional
      network and corresponding left hemisphere areas suggesting a compensatory
      recruitment of analogous contralesional areas. Interestingly, a more complex
      pattern of neural changes was observed in the fusiform gyri which have previously
      been implicated in lateralised directed spatial attention. There was an increase
      in the right hemisphere and a decrease in the left hemisphere. This pattern of
      recovery is reminiscent of a "push-pull" pattern previously described for the
      dorsal parietal cortex by Corbetta et al. (2005) in the recovery from spatial
      neglect.

PMID- 19096137
TI  - Improved sensorimotor function by rolipram following focal cerebral ischemia in
      rats.
AB  - PURPOSE: Rolipram, a specific phosphodiesterase 4 inhibitor (PDE4), is suggested
      to facilitate functional recovery following brain injury by activation of
      cAMP/CREB pathway. We examined the effect of rolipram on sensorimotor recovery in
      rats following transient occlusion of the middle cerebral artery (MCAO). METHODS:
      Rats were subjected to transient MCAO for 2 h. Rolipram was administered at a
      dose of 0.1 or 1 mg/kg (i.p., twice a day, for 13 days) starting administration
      on postoperative day 2. Sensorimotor outcome was assessed using limb-placing,
      beam-walking and cylinder tests at baseline and 7, 14, and 21 days after MCAO.
      RESULTS: Rolipram decreased locomotor activity and rearing, produced atypical
      head twitches, and possible hyperalgesia immediately after treatments, which were
      all considered as acute side effects. The analysis of hindlimb function utilizing
      beam-walking tests showed that overall performance was impaired in MCAO vehicle
      rats (p < 0.01) and MCAO rats treated with rolipram, at a dose of 0.1 mg/kg (p <
      0.01), compared to sham-operated rats. Interestingly, MCAO rats treated with
      rolipram at a dose of 1.0 mg/kg had significantly fewer slips when traversing an
      elevated beam than those treated with a dose of 0.1 mg/kg (p < 0.05) indicating
      improved sensorimotor function. More importantly, hindlimb function at the higher
      rolipram dose was not different from sham-operated rats after cessation of drug
      treatment at day 21. There was a significant group effect (p < 0.001) in the
      cylinder test, however, this was due to the decreased use of the impaired
      forelimb in MCAO rats compared to sham-operated rats at day 7, 14 and 21. In
      addition, MCAO rats treated with rolipram seemed to use their impaired forelimbs
      less compared to MCAO controls. Limb-placing performance was severely impaired
      but not different among MCAO rats. CONCLUSIONS: The present data suggest that
      rolipram provides some improvement in sensorimotor recovery in MCAO rats possibly
      by augmenting cAMP/CREB signalling, but this is masked by its side effects.

PMID- 19096138
TI  - Dimethyl sulfoxide provides neuroprotection in a traumatic brain injury model.
AB  - PURPOSE: The objective of this study was to evaluate the neuroprotective
      potential of the antioxidant, curcumin compared to alpha-tocopherol in a rat
      model of traumatic brain injury (TBI). METHODS: Male Sprague-Dawley rats were
      administered curcumin (3, 30, 300 mg/kg), alpha-tocopherol (100 mg/kg), DMSO
      vehicle, or saline, 30 min prior to and 30 and 90 min after moderate lateral
      fluid percussion TBI. Rats were euthanized at 24 hours after injury and coronal
      brain sections were stained with Fluoro-Jade to identify degenerating neurons.
      Degenerating neurons in the CA2-3 sector of the dorsal hippocampus were
      quantified in 10 sections spaced 300 microm apart in each rat. RESULTS: One way
      ANOVA revealed a significant difference (p = 0.01) between groups. The curcumin,
      alpha-tocopherol, and DMSO groups had significantly reduced numbers of
      degenerating neurons compared to the saline-treated group. No significant
      differences were observed between any of the drug treatment groups or the DMSO
      group. CONCLUSIONS: Since protection in the DMSO vehicle group was equal to that
      of the experimental groups, no conclusions about neuroprotection regarding alpha
      tocopherol or curcumin can be made from this study. The results suggest that DMSO
      may be acting as an overriding neuroprotectant in this experiment. We conclude
      that DMSO is a viable neuroprotective agent against secondary cell death in TBI.

PMID- 19096139
TI  - Retrograde viral transduction of cortical pyramidal neurons from the spinal cord.
AB  - PURPOSE: The primary motor pathway, the corticospinal tract, is a major target
      for spinal cord regeneration studies. One way of improving the regeneration of
      corticospinal axons is to introduce regeneration-associated genes into cortical
      motor neurons using viral vector delivery. METHODS: We used an engineered Herpes
      Simplex virus (HSV1) with the EF1alpha promoter encoding either LacZ or GFP to
      transduce cortical neurons through retrograde transport following the injection
      of vector into adult rat striatum or spinal cord. After three-days to one-month
      post-injection, sections of brain and spinal cord were viewed with fluorescence
      microscopy or processed for LacZ histochemistry. RESULTS: Many layer V motor
      cortical neurons were transduced following striatal injections. These were not
      corticospinal neurons as they were not fluorogold-labelled following tracer
      injection into spinal cord. Corticospinal neurons in both hemispheres were,
      however, transduced following direct vector injections into the dorsal column of
      spinal cord, yielding 250-400 transduced corticospinal neurons per animal. No non
      pyramidal neurons or thalamic neurons were transduced by spinal injections.
      CONCLUSIONS: Therefore, this HSV1.EF1alpha vector is highly effective for the
      transduction of corticospinal neurons without direct injection into the brain and
      could be used to introduce regeneration-relevant genes into these neurons with
      the aim of regenerating the corticospinal tract.

PMID- 19096140
TI  - Visual hypo and hypergnosia as exemplars of poles of psychic tonus in the
      occipital lobes: multiple case analyses.
AB  - The "psychic tonus" model or PTM [1] of hemispheric specialization states that
      the left hemisphere is a psychic and behavioral activator and that the right
      hemisphere is an inhibitor. The PTM predicts that the tonus of visual
      representation ought to manifest hemispheric specialization in the occipital
      lobes. Specifically PTM predicts that pathological positive visual tonus (visual
      hallucination) ought to be associated more frequently with right occipital
      lesions. PTM also predicts that pathological negative visual tonus (loss of
      visual imagery) ought to result more often from left occipital lesions. We
      reviewed 78 cases of post lesion hallucination and 12 cases of post lesion loss
      of evocation of images, all following a unilateral lesion. Analyses of these
      relevant previously published cases support the predictions. In accordance with
      previously published demonstrations of hemispheric specialization for auditory
      tonus in the temporal lobes and for somesthetic tonus in the parietal lobes, the
      present findings extend the psychic tonus model of hemispheric specialization to
      vision in the occipital lobes.

PMID- 19096141
TI  - Dysgraphia in patients with primary lateral sclerosis: a speech-based rehearsal
      deficit?
AB  - The present study aims to demonstrate that errors when writing are more common
      than expected in patients affected by primary lateral sclerosis (PLS) with severe
      dysarthria or complete mutism, independent of spasticity. Sixteen patients
      meeting Pringle's et al. [34] criteria for PLS underwent standard
      neuropsychological tasks and evaluation of writing. We assessed writing abilities
      in spelling through dictation in which a set of words, non-words and short
      phrases were presented orally and by composing words using a set of preformed
      letters. Finally, a written copying task was performed with the same words.
      Relative to controls, PLS patients made a greater number of spelling errors in
      all writing conditions, but not in copy task. The error types included:
      omissions, transpositions, insertions and letter substitutions. These were
      equally distributed on the writing task and the composition of words with a set
      of preformed letters. This pattern of performance is consistent with a spelling
      impairment. The results are consistent with the concept that written production
      is critically dependent on the subvocal articulatory mechanism of rehearsal,
      perhaps at the level of retaining the sequence of graphemes in a graphemic
      buffer. In PLS patients a disturbance in rehearsal opportunity may affect the
      correct sequencing/assembly of an orthographic representation in the written
      process.

PMID- 19096142
TI  - Crossed aphasia and visuo-spatial neglect following a right thalamic stroke: a
      case study and review of the literature.
AB  - Crossed aphasia in dextrals (CAD) following pure subcortical lesions is rare.
      This study describes a right-handed patient with an ischemic lesion in the right
      thalamus. In the post-acute phase of the stroke, a unique combination of 'crossed
      thalamic aphasia' was found with left visuo-spatial neglect and constructional
      apraxia. On the basis of the criteria used in Marien et al. [67], this case
      report is the first reliable representative of vascular CAD following an isolated
      lesion in the right thalamus. Furthermore, this paper presents a detailed
      analysis of linguistic and cognitive impairments of 'possible' and 'reliable'
      subcortical CAD-cases published since 1975. Out of 25 patients with a pure
      subcortical lesion, nine cases were considered as 'possibly reliable or
      reliable'. A review of these cases reveals that: 1) demographic data are
      consistent with the general findings for the entire group of vascular CAD, 2) the
      neurolinguistic findings do not support the data in the general CAD-population
      with regard to a) the high prevalence of transcortical aphasia and b) the
      tendency towards a copresence of an oral versus written language dissociation and
      a 'mirror-image' lesion-aphasia profile, 3) subcortical CAD is not a transient
      phenomenon, 4) the lesion-aphasia correlations are not congruent with the high
      incidence of anomalous cases in the general CAD-population, 5) neuropsychological
      impairments may accompany subcortical CAD.

PMID- 19096143
TI  - Foreign accent syndrome mimicked by Garcin syndrome with spontaneous resolution.
AB  - An English speaking women developed a French accent, without any aphasic
      syndromes, in conjunction with multiple left sided cranial nerve deficits,
      temporally related to cranial trauma. Extensive testing with multimodality
      magnetic resonance imaging, cerebrospinal fluid and laboratory analysis was
      unremarkable. She was followed over a 3 year period during which her French
      accent resolved as did the majority of her multiple unilateral cranial
      neuropathies. The neurological diagnoses included a foreign accent syndrome
      attributed to a reversible Garcin syndrome.

PMID- 19096144
TI  - Delusion of pregnancy in frontotemporal lobar degeneration with motor neurone
      disease (FTLD/MND).
AB  - Psychotic phenomena such as delusions and hallucinations are rare in
      frontotemporal dementia syndromes but have recently been recognised as an early
      feature in some cases of frontotemporal lobar degeneration with motor neurone
      disease (FTLD/MND). A patient with delusion of pregnancy as an early feature of
      FTLD/MND is presented to illustrate the need to consider neurodegenerative
      disease as well as primary psychiatric disorder as the underlying cause of this
      striking symptom.

PMID- 19096145
TI  - HER-2/neu amplification testing in breast cancer by multiplex ligation-dependent
      probe amplification in comparison with immunohistochemistry and in situ
      hybridization.
AB  - BACKGROUND: Assessment of HER-2/neu status in invasive breast cancer is crucial
      to establish eligibility for trastuzumab and taxane based chemotherapy. Next to
      immunohistochemistry (IHC) to evaluate protein overexpression, a second line gene
      amplification test is required for cases with equivocal protein expression. This
      study aimed to validate a new PCR based test, called Multiplex Ligation-dependent
      Probe Amplification (MLPA), as a simple and quick method to assess HER-2/neu gene
      amplification status in invasive breast cancer. METHODS: MPLA results were
      compared with gene amplification status assessed by fluorescence in situ
      hybridization (FISH) and chromogenic in situ hybridization (CISH) as gold
      standard, and with protein overexpression by IHC in 518 breast carcinoma
      patients. RESULTS: About 10% of cases overexpressed HER-2/neu at the protein
      level (IHC), and 11% of cases showed gene-amplification by MLPA. A high
      concordance was found between FISH and CISH, MLPA and IHC, and MLPA and CISH.
      MLPA showed amplification in 7/36 (19%) of the equivocal IHC 2+ cases. However,
      of the IHC 0/1+ cases, 6/434 (1.4%) were also amplified by MLPA, and
      amplification was confirmed in all of these cases by FISH/CISH. On the other
      hand, one of the 48 (2%) IHC 3+ cases was normal by MLPA and lack of
      amplification was confirmed by FISH/CISH. CONCLUSION: MLPA is a fast, accurate
      and cheap method to detect breast cancer HER-2/neu amplification in small
      quantities of DNA extracted from paraffin blocks, and thereby a reliable
      alternative to FISH and CISH.

PMID- 19096146
TI  - Quantitative fluorescence determination of long-fragment DNA in stool as a marker
      for the early detection of colorectal cancer.
AB  - BACKGROUND: A variety of molecular markers have been evaluated for the
      development of a non-invasive approach to the diagnosis of colorectal cancer. We
      aimed to validate the diagnostic accuracy, using the same threshold as in the
      previous pilot study, of fluorescent long DNA test as a relatively simple and
      inexpensive tool for colorectal cancer detection. METHODS: A case-control study
      was conducted on 100 healthy subjects and 100 patients at first diagnosis of
      colorectal cancer. Human long-fragment DNA in stool was quantified by
      fluorescence primers and a standard curve and expressed in DNA nanograms.
      RESULTS: We validated the 25-ng value, which emerged as the most accurate cut-off
      in the pilot study, obtaining 79% (95% CI, 71-87%) sensitivity and 89% (95% CI,
      83-95%) specificity. Specificity was very high for all cut-off values (15-40 ng)
      analyzed, ranging from 78 to 96%. Sensitivity was only slightly lower, reaching
      84% at the lowest cut-off and maintaining a good level at the higher values.
      Diagnostic potential was independent of gender, age and tumor site. CONCLUSION:
      Fecal DNA analysis is a non-invasive and fairly simple test showing high
      diagnostic potential. These characteristics, together with the small amount of
      stool required, make it potentially suitable to be used alongside or as an
      alternative to current non-invasive screening approaches. Our next step will be
      to validate these results in a large-scale cohort study of a screening
      population, which is needed prior to implementation into clinical practice.

PMID- 19096147
TI  - Potential biomarkers of colorectal adenoma-dysplasia-carcinoma progression: mRNA
      expression profiling and in situ protein detection on TMAs reveal 15 sequentially
      upregulated and 2 downregulated genes.
AB  - BACKGROUND: As most colorectal cancers (CRC) develop from villous adenomas,
      studying alterations in gene expression profiles across the colorectal adenoma
      dysplasia-carcinoma sequence may yield potential biomarkers of disease
      progression. METHODS: Total RNA was extracted, amplified, and biotinylated from
      colonic biopsies of 15 patients with CRC, 15 with villous adenoma and 8 normal
      controls. Gene expression profiles were evaluated using HGU133Plus2.0 microarrays
      and disease progression associated data were validated with RT-PCR. The potential
      biomarkers were also tested at the protein level using tissue microarray samples
      of 103 independent and 16 overlapping patients. RESULTS: 17 genes were validated
      to show sequentially altered expression at mRNA level through the normal-adenoma
      dysplasia-carcinoma progression. Prostaglandin-D2 receptor (PTGDR) and amnionless
      homolog (AMN) genes revealed gradually decreasing expression while the rest of 15
      genes including osteonectin, osteopontin, collagen IV-alpha 1, biglycan, matrix
      GLAprotein, and von Willebrand factor demonstrated progressively increasing
      expression. Similar trends of expression were confirmed at protein level for
      PTGDR, AMN, osteopontin and osteonectin. CONCLUSIONS: Downregulated AMN and PTGDR
      and upregulated osteopontin and osteonectin were found as potential biomarkers of
      colorectal carcinogenesis and disease progression to be utilized for prospective
      biopsy screening both at mRNA and protein levels. Gene alterations identified
      here may also add to our understanding of CRC progression.

PMID- 19096148
TI  - Genomic profiling by array comparative genomic hybridization reveals novel DNA
      copy number changes in breast phyllodes tumours.
AB  - Breast phyllodes tumour (PT) is a rare fibroepithelial tumour. The genetic
      alterations contributing to its tumorigenesis are largely unknown. To identify
      genomic regions involved in pathogenesis and progression of PTs we obtained
      genome-wide copy number profiles by array comparative genomic hybridization
      (CGH).DNA was isolated from fresh-frozen tissue samples. 11 PTs and 3
      fibroadenomas, a frequently occurring fibroepithelial breast tumour, were
      analyzed. Arrays composed of 2464 genomic clones were used, providing a
      resolution of ~1.4 Mb across the genome. Each clone contains at least one STS for
      linkage to the human genome sequence.No copy number changes were detected in
      fibroadenomas. On the other hand, 10 of 11 PT (91%) showed DNA copy number
      alterations. The mean number of chromosomal events in PT was 5.5 (range 0-16) per
      case. A mean of 2.0 gains (range 0-10) and 3.0 losses (range 0-9) was seen per
      case of PT. Three cases showed amplifications. DNA copy number change was not
      related to PT grade. We observed recurrent loss on chromosome 1q, 4p, 10, 13q,
      15q, 16, 17p, 19 and X. Recurrent copy number gain was seen on 1q, 2p, 3q, 7p,
      8q, 16q, 20.In this study we used array CGH for genomic profiling of
      fibroepithelial breast tumours. Whereas most PT showed chromosomal instability,
      fibroadenomas lacked copy number changes. Some copy number aberrations had not
      previously been associated with PT. Several well-known cancer related genes, such
      as TP53 and members of the Cadherin, reside within the recurrent regions of copy
      number alteration. Since copy number change was found in all benign PT, genomic
      instability may be an early event in PT genesis.

PMID- 19096149
TI  - TGF-beta repressors SnoN and Ski are implicated in human colorectal
      carcinogenesis.
AB  - BACKGROUND: The TGF-beta signaling repressors SnoN and Ski have been critically
      implicated in human cancer. METHODS: To explore the role of SnoN and Ski in the
      development and progression of colorectal cancer we examined their protein
      expression profile by immunohistochemistry in a series of human colorectal
      adenomas, carcinomas and lymph node metastases. The mRNA expression of SnoN was
      also quantified by Real-Time RT-PCR. RESULTS: SnoN and Ski were overexpressed
      both in adenomas with severe dysplasia and colorectal carcinomas. Protein
      expression was cytoplasmic and nuclear with predominant cytoplasmic localization.
      The subcellular localization was related differently to pathologic variables of
      colorectal carcinomas. Although there was no significant association of protein
      levels with tumor invasion and metastasis, a significant correlation of nuclear
      SnoN and Ski with beta-catenin pathway was observed. Moreover, SnoN mRNA did not
      differ in carcinomas as compared to normal control and there was no correlation
      between SnoN protein and mRNA levels. CONCLUSION: Our findings suggest that SnoN
      and Ski exert oncogenic effects in human colorectal carcinogenesis and their
      overexpression is implicated in early stage disease.

PMID- 19096150
TI  - No evidence for FANCF gene silencing in head-and-neck squamous cell carcinomas.

PMID- 19096151
TI  - Multiple numerical chromosome aberrations in carcinogenesis: the kidney cancer
      model.

PMID- 19096152
TI  - David Paul Hansemann: chromosomes and the origin of the cancerous features of
      tumor cells.

PMID- 19096153
TI  - Animal models of Alzheimer's disease: therapeutic implications.
AB  - This Special Issue of the Journal of Alzheimer's Disease (JAD) provides an
      overview of animal models of Alzheimer's disease (AD). Very few species
      spontaneously develop the cognitive, behavioral, and neuropathological symptoms
      of AD, yet AD research must progress at a more rapid pace than the rate of human
      aging. In recent years, a variety of models have been created--from tiny
      invertebrates with life spans measurable in months to huge mammals that live
      several decades. The fruit fly, Drosophila melanogaster, is a powerful genetic
      tool that has recently emerged as a model of AD with neural features and
      assessable learning and memory. Transgenic mice are the most widely used animal
      models of AD and have yielded significant research breakthroughs. Accelerated
      aging seen in the SAMP8 mouse is a non-transgenic model with great utility. Rat
      models provided early evidence about the deleterious impact of amyloid-beta
      (Abeta) on neurons and continue to provide insights. Rabbits, as langomorphs, are
      more closely related to primates than are rodents and have conserved the sequence
      of Abeta in humans (as have canines and non-human primates). The
      hypercholesterolemic rabbit is an excellent AD model. The aging canine develops
      AD neuropathology spontaneously and is especially suitable for tests of
      therapeutics. Non-human primates are invaluable for the development of
      therapeutics translating to humans. Each animal model has limitations and
      strengths, but used together in complementary fashion, animal models for research
      on AD are essential for rapid progress toward a cure.

PMID- 19096154
TI  - Drosophila models of Alzheimer's amyloidosis: the challenge of dissecting the
      complex mechanisms of toxicity of amyloid-beta 42.
AB  - Alzheimer's disease (AD) is the most common form of senile dementia, and a cure
      is desperately needed. The amyloid-beta42 (Abeta42) has been suggested to play a
      central role in the pathogenesis of AD. However, the mechanism by which Abeta42
      causes AD remains unclear. To understand the pathogenesis and to develop
      therapeutic avenues, it is crucial to generate animal models of AD in genetically
      tractable organisms. Drosophila is a well-established model system for which
      abundant genetic tools are available. Moreover, its well organized brain permits
      the study of complex behaviors such as learning and memory. We have established
      transgenic flies that express human Abeta42 in the nervous system. These flies
      developed age-dependent short-term memory impairment and neurodegeneration. In
      this review, we will first describe transgenic Abeta42 fly models and discuss the
      unique features of this system compared to mouse AD models. Secondly, we will
      discuss the usage of the fly models to evaluate currently proposed therapeutic
      strategies. Thirdly, we will briefly review the results of a genetic screen for
      modifiers of Abeta42 toxicity in the fly model. Finally, we will discuss how to
      dissect the complex mechanisms of Abeta42 toxicity focusing on its aggregation
      propensity using the fly model system.

PMID- 19096155
TI  - Modeling Tauopathy in the fruit fly Drosophila melanogaster.
AB  - The fruit fly Drosophila melanogaster has emerged as a powerful system in which
      to model human disease. This review focuses on the utility of the fly to model
      tau-dependent neurodegeneration, a hallmark of Alzheimer's disease and related
      neurodegenerative disorders. I provide a detailed description of fly tauopathy
      models and summarize a number of studies that demonstrate their ability to
      recapitulate both primary features of tauopathy, including tau-induced
      neurodegeneration and phosphorylation, and secondary features, including
      oxidative stress, cell-cycle activation and changes in the actin cytoskeleton.
      Important genetic and biochemical insights are discussed, and future directions
      proposed.

PMID- 19096156
TI  - Anti-amyloid-beta immunotherapy in Alzheimer's disease: relevance of transgenic
      mouse studies to clinical trials.
AB  - Therapeutic approaches to the treatment of Alzheimer's disease are focused
      primarily on the amyloid-beta peptide which aggregates to form amyloid deposits
      in the brain. The amyloid hypothesis states that amyloid is the precipitating
      factor that results in the other pathologies of Alzheimer's disease. One such
      therapy that has attracted significant attention is anti-amyloid-beta
      immunotherapy. First described in 1999, immunotherapy uses anti-amyloid-beta
      antibodies to lower brain amyloid levels. Active and passive immunization were
      shown to lower brain amyloid levels and improve cognition in multiple transgenic
      mouse models. Mechanisms of action were studied in these mice and revealed a
      complex set of mechanisms that depended on the type of antibody used. When active
      immunization advanced to clinical trials a subset of patients developed
      meningoencephalitis, an event not predicted in mouse studies. It was suspected
      that a T-cell response due to the type of adjuvant used was the cause. Passive
      immunization has also advanced to Phase III clinical trials on the basis of
      successful transgenic mouse studies. Reports from the active immunization
      clinical trial indicated that, similarly to effects observed in mouse studies,
      amyloid levels in brain were reduced.

PMID- 19096157
TI  - The effects of NOS2 gene deletion on mice expressing mutated human AbetaPP.
AB  - Nitric oxide synthase 2 (NOS2) and its gene product, inducible NOS (iNOS) play an
      important role in neuroinflammation by generating nitric oxide (NO), a critical
      signaling and redox factor in the brain. Although NO is associated with tissue
      damage, it can also promote cell survival. We hypothesize that during long-term
      exposure to amyloid-beta (Abeta) in Alzheimer's disease (AD), NO levels fall in
      the brain to a threshold at which the protective effects of NO cannot be
      sustained, promoting Abeta mediated damage. Two new mouse models of AD have been
      developed that utilize this concept of NO's action. These mice express human
      amyloid-beta protein precursor (AbetaPP) mutations that generate Abeta peptides
      on a mouse NOS2 knockout background. The APP/NOS2(-/-) bigenic mice progress from
      Abeta production and amyloid deposition to hyperphosphorylated normal mouse tau
      at AD-associated epitopes, aggregation and redistribution of tau to
      somatodendritic regions of neurons and significant neuronal loss including loss
      of interneurons. This AD-like pathology is accompanied by robust behavioral
      changes. As APP/NOS2(-/-) bigenic mice more fully model the human AD disease
      pathology, they may serve as a tool to better understand disease progression in
      AD and the role of NO in altering chronic neurological disease processes.

PMID- 19096159
TI  - Apparent behavioral benefits of tau overexpression in P301L tau transgenic mice.
AB  - Transgenic mice expressing human tau containing the P301L tau mutation (JNPL3;
      tau mice) develop motor neuron loss, paralysis and death between 7 and 12 months.
      Surprisingly, at 5 and 7 months of age, tau transgenic mice were superior to
      other genotypes in the rotarod task, and had near perfect scores on the balance
      beam and coat hanger tests. One tau transgenic mouse was performing at a superior
      level in the rotarod one day prior to developing paralysis. Cognitive function
      was also normal in the tau mice evaluated in the radial arm water maze and the Y
      maze tasks. We also crossed the tau transgenic mice with Tg2576 amyloid-beta
      protein precursor (AbetaPP) transgenic mice. Although AbetaPP mice were deficient
      in the radial arm maze task, AbetaPP + tau mice were not impaired, implying a
      benefit of the tau transgene. Some mice were homozygous for the retinal
      degeneration mutation (rd/rd) and excluded from the genotype analysis. Only the
      water maze task discriminated the rd/rd mice from nontransgenic mice. In
      conclusion, it seems that the modest tau overexpression or the presence of mutant
      tau in the JNPL3 tau mice may provide some benefit with respect to motor and
      cognitive performance before the onset of paralysis.

PMID- 19096158
TI  - Estrogen and hippocampal plasticity in rodent models.
AB  - Accumulating evidence indicates that ovarian hormones regulate a wide variety of
      non-reproductive functions in the central nervous system by interacting with
      several molecular and cellular processes. A growing animal literature using both
      adult and aged rodent models indicates that 17beta-estradiol, the most potent of
      the biologically relevant estrogens, facilitates some forms of learning and
      memory, in particular those that involve hippocampal-dependent tasks. A recently
      developed triple-transgenic mouse (3xTg-AD) has been widely used as an animal
      model of Alzheimer's disease, as this mouse exhibits an age-related and
      progressive neuropathological phenotype that includes both plaque and tangle
      pathology mainly restricted to hippocampus, amygdala and cerebral cortex. In this
      report, we examine recent studies that compare the effects of ovarian hormones on
      synaptic transmission and synaptic plasticity in adult and aged rodents. A better
      understanding of the non-reproductive functions of ovarian hormones has far
      reaching implications for hormone therapy to maintain health and function within
      the nervous system throughout aging.

PMID- 19096160
TI  - From aging to Alzheimer's disease: unveiling "the switch" with the senescence
      accelerated mouse model (SAMP8).
AB  - Current mouse models of Alzheimer's disease (AD) are restricted to the expression
      of AD-related pathology associated with specific mutations present in early-onset
      familial AD and thus represent < 5% of AD cases. To date there are no mouse lines
      that model late-onset/age-related AD, the feature which accounts for the vast
      majority of cases. As such, based on current mutation-associated models, the
      chronology of events that lead to the disease in the aged population is difficult
      to establish. However, published data show that senescence-accelerated mouse
      (SAMP8), as a model of aging, display many features that are known to occur early
      in the pathogenesis of AD such as increased oxidative stress, amyloid-beta
      alterations, and tau phosphorylation. Therefore, SAMP8 mice may be an excellent
      model for studying the earliest neurodegenerative changes associated with AD and
      provide a more encompassing picture of human disease, a syndrome triggered by a
      combination of age-related events. Here, the neurochemical, neuropathological,
      and behavioral alterations, characterized in SAMP8 mice are critically reviewed
      and discussed in relation to the potential use of this mouse model in the study
      of AD pathogenesis.

PMID- 19096162
TI  - The early and ongoing experience with the cholesterol-fed rabbit as a model of
      Alzheimer's disease: the old, the new and the pilot.
AB  - Pioneering autopsy studies revealed a possible link between coronary artery
      disease, cholesterol and Alzheimer's disease (AD). In the cholesterol-fed rabbit
      model of human coronary artery disease, we identified numerous neuropathologic
      features of AD including central accumulation of amyloid-beta (Abeta) and
      cognitive deficits compared to rabbits fed unaltered diet. Removing cholesterol
      from the diet or treatment with cholesterol-lowering medications reversed the
      severity of AD-like alterations. This fostered the rationale for testing a
      cholesterol-lowering statin medication for benefit in the treatment of AD.
      Further studies suggested that the cholesterol-fed rabbit was a viable model for
      AD, but the severity of the neuropathology produced exhibited gender-related
      differences. Furthermore the induction of AD-like neuropathology by dietary
      cholesterol was found to depend on the quality of water the animal was drinking.
      Cholesterol-fed rabbits drinking distilled water showed minimal central changes,
      whereas animals drinking distilled water supplemented with low levels of copper
      were severely affected. It was clear that cholesterol caused the over-production
      of Abeta in the brain and copper influenced its clearance to the blood. Emerging
      data suggest that low-density lipoprotein receptor-related protein-1 (LRP) on
      brain capillaries clears Abeta from brain and that excess circulating copper
      negatively influences this process.

PMID- 19096161
TI  - Use of copper and insulin-resistance to accelerate cognitive deficits and
      synaptic protein loss in a rat Abeta-infusion Alzheimer's disease model.
AB  - The rat amyloid-beta (Abeta) intracerebroventricular infusion can model aspects
      of Alzheimer's disease (AD) and has predicted efficacy of therapies such as
      ibuprofen and curcumin in transgenic mouse models. High density lipoprotein
      (HDL), a normal plasma carrier of Abeta, is used to attenuate Abeta aggregation
      within the pump, causing Abeta-dependent toxicity and cognitive deficits within 3
      months. Our goal was to identify factors that might accelerate onset of Abeta
      dependent deficits to improve efficiency and cost-effectiveness of model. We
      focused on: 1) optimizing HDL-Abeta preparation for maximal toxicity; 2)
      evaluating the role of copper, a factor typically in water that can impact
      oligomer stability; and 3) determining impact of insulin resistance (type II
      diabetes), a risk factor for AD. In vitro studies were performed to determine
      doses of copper and methods of Abeta-HDL preparation that maximized toxicity.
      These preparations when infused resulted in earlier onset of cognitive deficits
      within 6 weeks post-infusion. Induction of insulin resistance did not exacerbate
      Abeta-dependent cognitive deficits, but did exacerbate synaptic protein loss. In
      summary, the newly described in vivo infusion model may be useful cost-effective
      method for screening for new therapeutic drugs for AD.

PMID- 19096163
TI  - Immunotherapy for Alzheimer's disease: harnessing our knowledge of T cell biology
      using a cholesterol-fed rabbit model.
AB  - This timely special issue of the Journal of Alzheimer's Disease provides the
      opportunity to examine interfaces between basic science and clinical medicine
      using animal models to develop more effective therapies for the treatment and,
      ideally, prevention of Alzheimer's disease (AD). That some patients with AD
      enrolled in a clinical trial to inoculate against amyloid-beta (Abeta)
      experienced a misdirected polarization of Th cells reminds us that our knowledge
      of T cell biology, immune regulation, and the precise functional properties of
      adjuvants is incomplete. We review this knowledge and consider the advantages of
      the rabbit for immunological studies. The langomorph species is proximate to
      primates on the phylogenetic scale, its amino acid sequence of Abeta is 97%
      identical to the human Abeta sequence, and the rabbit model system is extensively
      characterized on a form of associative learning with parallels in normal aging in
      rabbits and humans that is severely impaired in human AD. Cholesterol-fed rabbits
      treated with Abeta immunotherapy generate high titer anti-Abeta responses. The
      cholesterol-fed rabbit model of AD with its close parallels to human genetics and
      physiology, along with its validity from molecular to cognitive levels as a model
      of human AD, provides a promising vehicle for development of immunotherapies.

PMID- 19096165
TI  - The canine (dog) model of human aging and disease: dietary, environmental and
      immunotherapy approaches.
AB  - Aged dogs (beagles) develop losses in executive function, learning and memory.
      The severity of decline in these cognitive domains represents a spectrum that
      captures normal aging, mild cognitive impairment and early/mild Alzheimer's
      disease (AD) in humans. In parallel, dogs naturally accumulate several types of
      neuropathology (although not all) consistent with human brain aging and AD
      including cortical atrophy, neuron loss, loss of neurogenesis, amyloid-beta
      (Abeta) plaques, cerebral amyloid angiopathy and oxidative damage. Many of these
      neuropathological features correlate with the extent of cognitive decline in a
      brain region-dependent manner. Dogs are ideally suited for longitudinal studies,
      and we provide a summary of the beneficial effects of an antioxidant diet,
      behavioral enrichment, and Abeta immunotherapy. In addition, combinatorial
      treatment approaches can be a powerful strategy for improving brain function
      through enhancement of multiple molecular pathways.

PMID- 19096164
TI  - Potential mechanisms linking cholesterol to Alzheimer's disease-like pathology in
      rabbit brain, hippocampal organotypic slices, and skeletal muscle.
AB  - Epidemiological, animal, and cellular studies suggest that abnormalities in
      cholesterol metabolism are important in the pathogenesis of Alzheimer's disease
      (AD), potentially by increasing amyloid-beta (Abeta) peptide levels. Accumulation
      of Abeta in the brain is suggested to play a key role in the neurodegenerative
      processes by triggering the hyperphosphorylation of tau and the neuronal death
      that develop in the course of AD. However, the mechanisms by which cholesterol
      increases Abeta levels are still ill-defined. Previous and ongoing work from our
      laboratory indicates that hypercholesterolemia leads to the increased neuronal
      content of cholesterol and increased levels and processing of the amyloid-beta
      protein precursor (AbetaPP). We also have found that the oxidized cholesterol
      metabolite, 27-hydroxycholesterol, increases Abeta levels in both organotypic
      hippocampal slices and in neuronal preparations cultured from adult rabbits. This
      cholesterol metabolite is predominantly formed in the circulation and, in
      contrast to cholesterol, has the ability to cross into the brain. These results
      may indicate that 27-hydroxycholesterol is the link between circulating
      cholesterol and AD-like pathology in the brain. We also have found pathological
      hallmarks in the skeletal muscle of cholesterol-fed rabbits that are suggestive
      of inclusion body myositis, a disease that shares some pathological similarities
      with AD.

PMID- 19096166
TI  - Estimation of working memory in macaques for studying drugs for the treatment of
      cognitive disorders.
AB  - Non-human primates have served as subjects for studies of the cognition-enhancing
      potential of novel pharmacological agents for over 25 years. Only recently has a
      greater appreciation of the translational applicability of this model been
      realized. Though most Old-World monkeys do not appear to acquire an Alzheimer's
      like syndrome in old age, their value resides in the brain physiology they have
      in common with humans. Paradigms like the delayed matching-to-sample task
      engender behavior that models aspects of working memory that are substrates for
      the actions of cognition-enhancing drugs. Our studies have provided information
      relevant to factors that limit the effectiveness of clinical trial design for
      compounds that potentially improve cognition. For example, cognition-enhancing
      compounds from different pharmacological classes, when administered to monkeys,
      can exhibit remarkable pharmacodynamic effects that outlast the presence of the
      drug in the body. Studies with non-human primates also can provide information
      regarding dose ranges and individual subject sensitivity experienced in the
      clinic. Components of working memory are differentially sensitive to drug effects
      and may be characterized by different dose ranges for certain compounds, even
      within the same task. Examples are provided that underscore the possible
      idiosyncrasies of drug action in the pharmacology of cognition--which could be of
      critical importance in the design of clinical trials.

PMID- 19096167
TI  - Dynamic performance of the beam position monitor support at the SSRF.
AB  - Electron beam stability is very important for third-generation light sources,
      especially for the Shanghai Synchrotron Radiation Facility whose ground
      vibrations are much larger than those for other light sources. Beam position
      monitors (BPMs), used to monitor the position of the electron beam, require a
      greater stability than other mechanical structures. This paper concentrates on an
      investigation of the dynamic performance of the BPM support prototype. Modal and
      response analyses have been carried out by finite-element (FE) calculations and
      vibration measurements. Inconsistent results between calculation and measurement
      have motivated a change in the soft connections between the support and the
      ground from a ground bolt in the initial design to full grout. As a result the
      mechanical stability of the BPM support is greatly improved, showing an increase
      in the first eigenfrequency from 20.2 Hz to 50.2 Hz and a decrease in the ratio
      of the root-mean-square displacement (4-50 Hz) between the ground and the top of
      the support from 4.36 to 1.23 in the lateral direction. An example is given to
      show how FE analysis can guide the mechanical design and dynamic measurements
      (i.e. it is not just used as a verification method). Similar ideas can be applied
      to improve the stability of other mechanical structures.

PMID- 19096168
TI  - Diamond kinoform hard X-ray refractive lenses: design, nanofabrication and
      testing.
AB  - Motivated by the anticipated advantageous performance of diamond kinoform
      refractive lenses for synchrotron X-ray radiation studies, this report focuses on
      progress in designing, nanofabricating and testing of their focusing performance.
      The method involves using lift-off and plasma etching to reproduce a planar
      definition of numerically determined kinoform refractive optics. Tests of the
      focusing action of a diamond kinoform refractive lens at the APS 8-ID-I beamline
      demonstrate angular control of the focal spot.

PMID- 19096169
TI  - Upgrade of the CATS sample changer on FIP-BM30A at the ESRF: towards a
      commercialized standard.
AB  - An upgraded version of the sample changer ;CATS' (Cryogenic Automated Transfer
      System) that was developed on the FIP-BM30A beamline at the ESRF is presented. At
      present, CATS is installed at SLS (three systems), BESSY (one system), DLS (two
      systems) and APS (four systems for the LSCAT beamline). It consists mainly of an
      automated Dewar with an assortment of specific grippers designed to obtain a fast
      and reliable mounting/dismounting rate without jeopardizing the flexibility of
      the system. The upgraded system has the ability to manage any sample standard
      stored in any kind of puck.

PMID- 19096170
TI  - A combined microRaman and microdiffraction set-up at the European Synchrotron
      Radiation Facility ID13 beamline.
AB  - This article describes the current status of the microRaman set-up at the ID13
      beamline of the European Synchrotron Radiation Facility. This offers an in situ
      on-axis microprobe which has a common focal position to the X-ray microbeam and
      can collect spectral data simultaneously. It can also be used in an offline
      sample characterization role, both before and after beamline experiments. To
      demonstrate the application of microRaman spectroscopy within a beamline
      environment, a number of examples are given.

PMID- 19096171
TI  - Correlation between local vibrations and metal mass in AlB2-type transition-metal
      diborides.
AB  - Lattice vibrations have been investigated in TiB2, ZrB2 and HfB2 by temperature
      dependent extended X-ray absorption fine structure (EXAFS) experiments. Data
      clearly show that the EXAFS oscillations are characterized by an anomalous
      behavior of the Debye-Waller factor of the transition-metal-boron pair, which is
      suggested to be associated with a superposition of an optical mode corresponding
      to phonon vibrations induced by the B sublattice and an acoustic mode
      corresponding to the transition-metal (TM) sublattice. Data can be interpreted as
      a decoupling of the metal and boron vibrations observed in these transition-metal
      diborides (TMB2), a mechanism that may be responsible for the significant
      reduction of the superconducting transition temperature observed in these systems
      with respect to the parent MgB2 compound. The vibrational behavior of TM-TM bonds
      has also been investigated to study the occurrence of anisotropy and anomalies in
      the lattice vibrational behavior of TM-TM bonds.

PMID- 19096172
TI  - Temperature dependence of the Ho L2-edge XMCD spectra of Ho6Fe23.
AB  - An X-ray magnetic circular dichroism (XMCD) study performed at the Ho L2,3-edges
      in Ho6Fe23 as a function of temperature is presented. It is demonstrated that the
      anomalous temperature dependence of the Ho L2-edge XMCD signal is due to the
      magnetic contribution of Fe atoms. By contrast, the Ho L3-edge XMCD directly
      reflects the temperature dependence of the Ho magnetic moment. By combining the
      XMCD at both Ho L2- and L3-edges, the possibility of determining the temperature
      dependence of the Fe magnetic moment is demonstrated. Then, both microHo(T) and
      microFe(T) have been determined by tuning only the absorption L-edges of Ho. This
      result opens new possibilities of applying XMCD at these absorption edges to
      obtain quantitative element-specific magnetic information that is not directly
      obtained by other experimental tools.

PMID- 19096173
TI  - Hard X-ray phase-contrast imaging with the Compact Light Source based on inverse
      Compton X-rays.
AB  - The first imaging results obtained from a small-size synchrotron are reported.
      The newly developed Compact Light Source produces inverse Compton X-rays at the
      intersection point of the counter propagating laser and electron beam. The small
      size of the intersection point gives a highly coherent cone beam with a few
      milliradian angular divergence and a few percent energy spread. These
      specifications make the Compact Light Source ideal for a recently developed
      grating-based differential phase-contrast imaging method.

PMID- 19096174
TI  - Pressure study of monoclinic ReO2 up to 1.2 GPa using X-ray absorption
      spectroscopy and X-ray diffraction.
AB  - The crystal and local atomic structure of monoclinic ReO2 (alpha-ReO2) under
      hydrostatic pressure up to 1.2 GPa was investigated for the first time using both
      X-ray absorption spectroscopy and high-resolution synchrotron X-ray powder
      diffraction and a home-built B4C anvil pressure cell developed for this purpose.
      Extended X-ray absorption fine-structure (EXAFS) data analysis at pressures from
      ambient up to 1.2 GPa indicates that there are two distinct Re-Re distances and a
      distorted ReO6 octahedron in the alpha-ReO2 structure. X-ray diffraction analysis
      at ambient pressure revealed an unambiguous solution for the crystal structure of
      the alpha-phase, demonstrating a modulation of the Re-Re distances. The
      relatively small portion of the diffraction pattern accessed in the pressure
      dependent measurements does not allow for a detailed study of the crystal
      structure of alpha-ReO2 under pressure. Nonetheless, a shift and reduction in the
      (011) Bragg peak intensity between 0.4 and 1.2 GPa is observed, with correlation
      to a decrease in Re-Re distance modulation, as confirmed by EXAFS analysis in the
      same pressure range. This behavior reveals that alpha-ReO2 is a possible inner
      pressure gauge for future experiments up to 1.2 GPa.

PMID- 19096175
TI  - X-ray fluorescent CT imaging of cerebral uptake of stable-iodine perfusion agent
      iodoamphetamine analog IMP in mice.
AB  - Using X-ray fluorescent computed tomography (XFCT), the in vivo and ex vivo
      cerebral distribution of a stable-iodine-labeled cerebral perfusion agent,
      iodoamphetamine analog (127I-IMP), has been recorded in the brains of mice. In
      vivo cerebral perfusion in the cortex, hippocampus and thalamus was depicted at
      0.5 mm in-plane spatial resolution. Ex vivo XFCT images at 0.25 mm in-plane
      spatial resolution allowed the visualisation of the detailed structures of these
      regions. The quality of the XFCT image of the hippocampus was comparable with the
      125I-IMP autoradiogram. These results highlight the sensitivity of XFCT and its
      considerable potential to evaluate cerebral perfusion in small animals without
      using radioactive agents.

PMID- 19096176
TI  - First XANES evidence of a disorder-order transition in a spinel ferrite compound:
      nanocrystalline ZnFe2O4.
AB  - In situ Zn K-edge XANES experiments were performed to investigate the thermal
      evolution of the non-equilibrium state in nano-sized ZnFe2O4. The initially
      disordered ferrite was annealed under oxygen atmosphere and kept at temperatures
      of 673, 773 and 873 K. Modifications of the XANES features allowed the direct
      detection of the Zn local surrounding changes from Oh to Td symmetry.
      Quantitative analyses of these results were performed by using the principal
      component analysis approach. The ferrite inversion does not change until the
      activation barrier is overcome at Ta = 585 K. Above Ta, the Zn ions continuously
      change their environment to their normal equilibrium state. Isothermal treatments
      confirm that the Zn transference follows a first-order kinetic process. In
      addition, the thermal treatment produces a partial recrystallization that
      increases the average grain size from 13 to 50 nm and reduces the microstrain.
      The room-temperature magnetic state changes from ferrimagnetic to paramagnetic,
      while the blocking temperature increases after the treatment.

PMID- 19096177
TI  - The MX2 macromolecular crystallography beamline: a wiggler X-ray source at the
      LNLS.
AB  - The Brazilian Synchrotron Light Laboratory [Laboratorio Nacional de Luz
      Sincrotron (LNLS), Campinas, SP, Brazil] is the first commissioned synchrotron
      light source in the southern hemisphere. The first wiggler macromolecular
      crystallography beamline (MX2) at the LNLS has been recently constructed and
      brought into operation. Here the technical design, experimental set-up,
      parameters of the beamline and the first experimental results obtained at MX2 are
      described. The beamline operates on a 2.0 T hybrid 30-pole wiggler, and its
      optical layout includes collimating mirror, Si(111) double-crystal monochromator
      and toroidal bendable mirror. The measured flux density at the sample position at
      8.7 eV reaches 4.8 x 10(11) photons s(-1) mm(-2) (100 mA)(-1). The beamline is
      equipped with a MarResearch Desktop Beamline Goniostat (MarDTB) and 3 x 3
      MarMosaic225 CCD detector, and is controlled by a customized version of the Blu
      Ice software. A description of the first X-ray diffraction data sets collected at
      the MX2 LNLS beamline and used for macromolecular crystal structure solution is
      also provided.

PMID- 19096179
TI  - Selected techniques in diamond anvil cell crystallography: centring samples using
      X-ray transmission and rocking powder samples to improve X-ray diffraction image
      quality.
AB  - The distinct X-ray transmission profile obtained by scanning a sample in a
      diamond anvil cell across a collimated X-ray beam is used to monitor sample
      displacement brought about by rotation. This measured displacement can in turn be
      used to calculate, and subsequently correct, the sample position with respect to
      a centre of rotation. This centring method differs from others also based on
      transmission in that it does not require a 180 degrees sample rotation, nor does
      it require prior positioning of the rotation axis in the path of the X-ray beam.
      After a full description of the method, an example is presented together with an
      extended record of use to evaluate the method in a practical setting. The
      practice and benefits of rocking polycrystalline samples during X-ray exposure
      have also been quantitatively examined. Changing the orientation of the sample
      grains with respect to the incident beam yields the expected result of a more
      homogeneous intensity distribution along Debye rings. Interestingly, by limiting
      the amount of time large grains assume a particular orientation, rocking brings
      about the added effect of significantly reducing detector saturation. Sample
      rocking yields more reliable relative intensities, a more appropriate line shape
      and narrower line width. Data are presented for a calibration standard at ambient
      pressure as well as a research sample at high pressure.

PMID- 19096178
TI  - High-flux hard X-ray microbeam using a single-bounce capillary with doubly
      focused undulator beam.
AB  - A pre-focused X-ray beam at 12 keV and 9 keV has been used to illuminate a single
      bounce capillary in order to generate a high-flux X-ray microbeam. The BioCAT
      undulator X-ray beamline 18ID at the Advanced Photon Source was used to generate
      the pre-focused beam containing 1.2 x 10(13) photons s(-1) using a sagittal
      focusing double-crystal monochromator and a bimorph mirror. The capillary
      entrance was aligned with the focal point of the pre-focused beam in order to
      accept the full flux of the undulator beam. Two alignment configurations were
      tested: (i) where the center of the capillary was aligned with the pre-focused
      beam (;in-line') and (ii) where one side of the capillary was aligned with the
      beam (;off-line'). The latter arrangement delivered more flux (3.3 x 10(12)
      photons s(-1)) and smaller spot sizes (< or =10 microm FWHM in both directions)
      for a photon flux density of 4.2 x 10(10) photons s(-1) microm(-2). The
      combination of the beamline main optics with a large-working-distance
      (approximately 24 mm) capillary used in this experiment makes it suitable for
      many microprobe fluorescence applications that require a micrometer-size X-ray
      beam and high flux density. These features are advantageous for biological
      samples, where typical metal concentrations are in the range of a few ng cm(-2).
      Micro-XANES experiments are also feasible using this combined optical
      arrangement.

PMID- 19096180
TI  - A dedicated small-angle X-ray scattering beamline with a superconducting wiggler
      source at the NSRRC.
AB  - At the National Synchrotron Radiation Research Center (NSRRC), which operates a
      1.5 GeV storage ring, a dedicated small-angle X-ray scattering (SAXS) beamline
      has been installed with an in-achromat superconducting wiggler insertion device
      of peak magnetic field 3.1 T. The vertical beam divergence from the X-ray source
      is reduced significantly by a collimating mirror. Subsequently the beam is
      selectively monochromated by a double Si(111) crystal monochromator with high
      energy resolution (DeltaE/E approximately 2 x 10(-4)) in the energy range 5-23
      keV, or by a double Mo/B4C multilayer monochromator for 10-30 times higher flux (
      approximately 10(11) photons s(-1)) in the 6-15 keV range. These two
      monochromators are incorporated into one rotating cradle for fast exchange. The
      monochromated beam is focused by a toroidal mirror with 1:1 focusing for a small
      beam divergence and a beam size of approximately 0.9 mm x 0.3 mm (horizontal x
      vertical) at the focus point located 26.5 m from the radiation source. A plane
      mirror installed after the toroidal mirror is selectively used to deflect the
      beam downwards for grazing-incidence SAXS (GISAXS) from liquid surfaces. Two
      online beam-position monitors separated by 8 m provide an efficient feedback
      control for an overall beam-position stability in the 10 microm range. The beam
      features measured, including the flux density, energy resolution, size and
      divergence, are consistent with those calculated using the ray-tracing program
      SHADOW. With the deflectable beam of relatively high energy resolution and high
      flux, the new beamline meets the requirements for a wide range of SAXS
      applications, including anomalous SAXS for multiphase nanoparticles (e.g.
      semiconductor core-shell quantum dots) and GISAXS from liquid surfaces.

PMID- 19096181
TI  - A Geiger-mode avalanche photodiode array for X-ray photon correlation
      spectroscopy.
AB  - X-ray photon correlation spectroscopy (XPCS) provides an opportunity to study the
      dynamics of systems by measuring the temporal fluctuations in a far-field
      diffraction pattern. A two-dimensional detector system has been developed to
      investigate fluctuations in the frequency range of several Hz to kHz. The X-ray
      detector system consists of a thin 100 microm scintillation crystal coupled to a
      Geiger-mode avalanche photodiode array. In this article the elements of the
      system are detailed and the detector for XPCS measurements is demonstrated.

PMID- 19096182
TI  - Capturing molecular structural dynamics by 100 ps time-resolved X-ray absorption
      spectroscopy.
AB  - An experimental set-up for time-resolved X-ray absorption spectroscopy with 100
      ps time resolution at beamline NW14A at the Photon Factory Advanced Ring is
      presented. The X-ray positional active feedback to crystals in a monochromator
      combined with a figure-of-merit scan of the laser beam position has been utilized
      as an essential tool to stabilize the spatial overlap of the X-ray and laser
      beams at the sample position. As a typical example, a time-resolved XAFS
      measurement of a photo-induced spin crossover reaction of the tris(1,10
      phenanthrorine)iron(II) complex in water is presented.

PMID- 19096183
TI  - Focusing synchrotron radiation using a polycapillary half-focusing X-ray lens for
      imaging.
AB  - An imaging system based on a polycapillary half-focusing X-ray lens (PHFXRL) and
      synchrotron radiation source has been designed. The focal spot size and the gain
      in power density of the PHFXRL were 22 microm (FWHM) and 4648, respectively, at
      14.0 keV. The spatial resolution of this new imaging system was better than 5
      microm when an X-ray charge coupled device with a pixel size of 10.9 x 10.9
      microm was used. A fossil of an ancient biological specimen was imaged using this
      system.

PMID- 19096186
TI  - The CardioWest total artificial heart for chronic heart transplant rejection.
AB  - Mechanical circulatory support has been used to treat graft failure after heart
      transplantation, but in patients who needed mechanical circulatory support
      because of chronic rejection, we have suffered from the treatment because its
      outcome was catastrophic. Multiple organ failure was often caused by the addition
      of or increase in immunosuppressive medications, and it is known as a cause of
      the poor outcomes. The CardioWest total artificial heart was implanted for a case
      of chronic heart transplant rejection to enable complete withdrawal of
      immunosuppressive medication. The patient underwent re-heart transplantation,
      with a good result. This is a new therapeutic technique for chronic graft
      rejection.

PMID- 19096187
TI  - A case of massive pulmonary embolism with ST elevation in leads V1-4.
AB  - A 35-year-old man was referred to the emergency department after having a short
      syncopal episode while waiting for a Doppler scan of the lower extremities for a
      4-week history of a painful right leg. He had no significant past medical history
      and was a non-smoker. On presentation he had severe chest pain and dyspnea
      associated with diaphoresis, and was hemodynamically unstable. His initial
      electrocardiogram (ECG) showed ST segment elevations in leads V(1-4), mimicking
      an anteroseptal myocardial infarction. However, the angiography showed the
      coronary arteries were normal and the right main pulmonary artery was partially
      occluded by large pulmonary emboli. The ECG changes were recorded in detail which
      also pointed to the diagnosis of pulmonary embolism (PE). This case shows how a
      PE can mimic an anteroseptal myocardial infarction on ECG, and the
      physiopathology of the ST elevation in PE was discussed.

PMID- 19096188
TI  - Adenosine triphosphate exposes dormant pulmonary vein conduction responsible for
      recurrent atrial tachyarrhythmias: importance of evaluating the dormant
      conduction during the re-do ablation procedure.
AB  - A 61-year-old man suffered from atrial tachycardia (AT) following pulmonary vein
      isolation (PVI) treatment of atrial fibrillation. During a re-do procedure, all
      pulmonary veins (PVs) were isolated from the left atrium (LA) and programmed
      stimulation could not induce any atrial arrhythmias. Adenosine triphosphate
      exposed dormant PV-LA conduction at the right superior PV. PV firing during the
      reconnection caused AT with the same P-wave morphology as clinical AT. For 6
      months after the elimination of that dormant PV conduction, the patient has been
      free of any AT. Evaluation of dormant PV conduction was effective in curing the
      recurrent AT after PVI.

PMID- 19096189
TI  - Congenital atresia of the left main coronary artery associated with patent ductus
      arteriosus and aortic regurgitation.
AB  - Congenital left main coronary artery (LMCA) atresia is a rare anomaly and
      surgical revascularization is recommended once the diagnosis is confirmed. In
      some cases, LMCA atresia will coexist with other cardiac anomalies, mostly in
      pediatric patients. A 32-year-old woman had congenital LMCA atresia associated
      with patent ductus arteriosus (PDA), aortic regurgitation (AR), and moderate
      pulmonary hypertension. The PDA and AR were repaired surgically and the patient's
      symptoms improved. Coronary revascularization was not performed because the LCA
      was supplied by 2 large conus arteries, as "naturally occurring" bypass arteries.
      The patient remained asymptomatic at the 2.5-year follow-up visit. Given the
      positive outcome in this patient, surgical repair of the associated cardiac
      defect without coronary revascularization may be a reasonable approach for
      patients with congenital LMCA atresia, in which the left coronary arterial tree
      is supplied by other "naturally occurring" bypass arteries.

PMID- 19096190
TI  - Pioglitazone reduces the necrotic-core component in coronary plaque in
      association with enhanced plasma adiponectin in patients with type 2 diabetes
      mellitus.
AB  - BACKGROUND: Pioglitazone has a preventive effect on cardiovascular disease, but
      its ability to stabilize coronary plaque is unknown. METHODS AND RESULTS: A
      prospective, randomized trial was conducted in 54 patients with type 2 diabetes
      and stable angina pectoris, randomly assigned to either a pioglitazone group or
      control group. Non-culprit, angiographically mild-to-moderate obstructive lesions
      were examined with virtual histology intravascular ultrasound (VH-IVUS) at
      coronary intervention and 6 months later. In total, 42 lesions of 22 patients in
      the pioglitazone group and 44 lesions of 24 patients in the control group were
      analyzed. After 6 months, patients in the pioglitazone group had significantly
      improved blood sugar, high-sensitivity C-reactive protein, and plasma adiponectin
      levels. VH-IVUS analysis revealed that, although the total plaque-to-vessel
      volume was not changed in either group, the necrotic-core area had significantly
      decreased in the pioglitazone group (-4.6+/-5.9% vs 1.1+/-9.3%, P=0.001). There
      was a significant inverse correlation between the change in plasma adiponectin
      levels and the change in necrotic-core area (r=-0.46, P<0.0001). CONCLUSIONS:
      Pioglitazone may stabilize coronary plaque by reducing the necrotic-core
      component, in association with enhanced plasma adiponectin levels.

PMID- 19096191
TI  - Anxiety and poor social support are independently associated with adverse
      outcomes in patients with mild heart failure.
AB  - BACKGROUND: The impact of psychosocial states, such as depression or anxiety, and
      social support on the outcomes of stable outpatients with mild heart failure (HF)
      has not been evaluated in the "real world" clinical practice. METHODS AND
      RESULTS: In the present study, 139 patients with a prior history of admission for
      HF provided the baseline demographic, clinical, socio-environmental, and
      psychosocial information. Cardiac death or re-admission because of worsening of
      HF was monitored during the follow-up period of 1 year. The prevalence of
      depression and anxiety were 37% and 37%, respectively, in HF patients. Depression
      was independently associated with male (sbeta=-0.36, P=0.01), social ties
      (sbeta=0.22, P=0.04) and low social support (sbeta=-0.39, P<0.01). Anxiety was
      associated with alcohol drinking (sbeta=0.22, P=0.04), brain natriuretic peptide
      > or =200 pg/dl (sbeta=0.35, P<0.01), and low social support (sbeta=-0.28,
      P=0.01). Kaplan-Meier analysis demonstrated that patients with anxiety (log-lank
      test; P<0.01) and lower scores of social support (P<0.01) had a higher rate of HF
      related re-admission. CONCLUSIONS: Anxiety and low social support were
      independently associated with HF-related re-admission, which indicates the need
      for their inclusion in the assessment and management of HF.

PMID- 19096192
TI  - Effects of pretreatment with statins on infarct size in patients with acute
      myocardial infarction who receive fibrinolytic therapy.
AB  - BACKGROUND: Experimental studies suggest that statins promote vascular
      fibrinolysis, so statin treatment before the onset of acute myocardial infarction
      (AMI) may result in a smaller infarct size. METHODS AND RESULTS: The study group
      comprised 310 patients with AMI who received fibrinolysis within 12 h after
      symptom onset: 39 had received statin pretreatment (statin group) and 271 had not
      (non-statin group). Initial Thrombolysis In Myocardial Infarction (TIMI) flow
      grade did not differ between groups. Among 120 patients with initial TIMI flow
      grade 0/1, achievement of TIMI flow grade > or =2 after passing the guidewire
      through the culprit lesion was more frequent in the statin group (70% vs 35%,
      P=0.03). The final rate of TIMI flow grade 3 was higher in the statin group (95%
      vs 86%, P=0.11). Area under the curve (AUC) for creatine kinase (CK) was lower in
      the statin group (55,972+/-45,934 vs 84,195+/-84,276 IU . L(-1) . h(-1), P=0.04).
      Multivariate analysis revealed statin pretreatment as an independent negative
      predictor of larger infarct size as defined by the upper tertile of AUC for CK
      (odds ratio 0.25, 95% confidence interval 0.07-0.91, P=0.035). CONCLUSION: Statin
      pretreatment may enhance fibrinolysis and reduce infarct size in patients with
      AMI.

PMID- 19096193
TI  - Venous thromboembolism: deep vein thrombosis with pulmonary embolism, deep vein
      thrombosis alone, and pulmonary embolism alone.
AB  - BACKGROUND: There are few data on the differences between deep vein thrombosis
      (DVT) with pulmonary embolism (PE) (Group A) and without PE (Group B), and no
      recent data on the incidence of PE and DVT in Japan. METHODS AND RESULTS: The
      symptoms and findings of the lower extremities and risks for venous
      thromboembolism were compared between Groups A and B, and the numbers of new
      patients with PE and those with DVT in 2006 were calculated. DVT was found
      equally in left and right legs in Group A, but more frequently in left legs than
      in right legs in Group B. Proximal thrombus was more frequent in Group A than in
      Group B, and the number of cases of symptoms resulting from DVT was less in Group
      A than in Group B. Proximal DVT, DVT in the right leg, no symptoms, and younger
      age were related to the presence of PE. The calculated number of new patients
      with PE per year was 7,864 (3,492 cases in 1996), and that with DVT per year was
      14,674. CONCLUSION: DVT in patients with PE and those without PE differed in the
      site and symptoms. The calculated number of new patients with PE per year doubled
      in 1 decade in Japan.

PMID- 19096194
TI  - Preoperative left atrial emptying fraction is a powerful predictor of successful
      maze procedure.
AB  - BACKGROUND: The maze procedure for the treatment of atrial fibrillation (AF) is a
      widely used adjunctive therapy. It is necessary to define the precise indications
      for the procedure based on preoperative factors, but definitive parameters in
      terms of atrial function have not been well determined. METHODS AND RESULTS: In
      the present study, 55 consecutive patients undergoing the maze procedure for
      persistent AF in combination with operations for organic heart diseases were
      evaluated. After dividing the patients into successful (n=41) and unsuccessful
      procedure (n=14) groups, based on the postoperative rhythm, the preoperative left
      atrial (LA) emptying fraction measured by transthoracic 2-dimensional
      echocardiogram was compared between groups. The LA emptying fraction was
      calculated as [(LA maximum volume - LA minimum volume)/LA maximum volume]x100.
      The preoperative LA emptying fraction was higher in the successful procedure
      group than in the unsuccessful procedure group (31.2+/-8.5 vs 21.4+/-10.9%,
      P=0.0011). Based on receiver-perating characteristic curve analyses, LA emptying
      fraction >26% predicted successful maze procedure with 70.7% sensitivity and
      78.6% specificity. CONCLUSIONS: LA emptying fraction should be considered in the
      precise indications of the maze procedure as adjunctive therapy.

PMID- 19096195
TI  - Di-(2-ethylhexyl) phthalate upregulates ATF3 expression and suppresses apoptosis
      in mouse genital tubercle.
AB  - OBJECTIVES: To investigate the effect of di-(2-ethylhexyl) phthalate (DEHP) on
      the expression of activating transcription factor 3 (ATF3) and apoptosis of fetal
      mouse genital tubercle (GT). METHODS: In this developmental toxicity study,
      pregnant C57BL/6 mice were exposed to corn oil or DEHP (100 or 500 mg/kg/day)
      from embryonic day 12 (ED12) to ED16. Apoptosis was characterized by Terminal
      transferase dUTP nick end labeling (TUNEL) assay. Using RT-PCR and western blot,
      the expressions of ATF3 and apoptosis-related genes (P53, Bcl-2 and Bax) were
      investigated. RESULTS: Apoptosis of fetal mouse GT cells notably decreased after
      DEHP treatment. DEHP activated ATF3 both at the mRNA and protein levels in GT.
      Furthermore, pro-apoptotic P53 was downregulated and the ratio of anti-apoptotic
      (Bcl-2)/pro-apoptotic (Bax) was not significantly changed. CONCLUSIONS: These
      results suggest that DEHP may induce external genital defects via a mechanism
      involving apoptosis, which might correlate with the regulation of ATF3 and P53
      expressions.

PMID- 19096196
TI  - Diffusion of health education programs with reference to health behavior theories
      in Japanese workplaces: present status and future plans.
AB  - OBJECTIVES: This study investigated the characteristics of health education
      programs and the health behavior theories used to establish more effective
      programs for Japanese companies. METHODS: The study surveyed 1,372 companies with
      500 or more employees. In a cross-sectional study, the characteristics of the
      health education programs were surveyed using a questionnaire, which included
      items regarding target lifestyle-related diseases and lifestyle areas, and the
      health behavior theories used to develop the present status and future plans.
      RESULTS: One hundred ninety companies responded giving a response rate of 13.8%.
      At the time of the survey, the most common diseases targeted for primary
      prevention were obesity (27.1%), hypertension (22.7%), hyperlipidemia (22.1%),
      and diabetes (22.1%). Approximately 60% of the respondents were implementing
      health education programs that targeted certain lifestyles, and the most
      frequently reported target lifestyles were diet (41.0%) and exercise (38.2%). At
      the time of the survey, 40% of respondents had implemented programs that included
      health behavior theory, and 55.6% were going to implement such program plans in
      the future, a significantly higher percentage than at the time of the survey.
      CONCLUSIONS: In Japanese workplaces, it has been suggested that programs that
      include health behavior theories have not been implemented frequently enough, but
      such programs are expected to become more common in the future. The findings of
      this survey may be useful for planning health education programs using health
      behavior theories to establish more effective programs for Japanese companies.

PMID- 19096197
TI  - Reliability and validity of the Japanese version of the Organizational Justice
      Questionnaire.
AB  - OBJECTIVES: Previous European studies reporting low procedural justice and low
      interactional justice were associated with increased health problems have used a
      modified version of the Moorman's Organizational Justice Questionnaire (OJQ,
      Elovainio et al., 2002) to assess organizational justice. We translated the
      modified OJQ into the Japanese language and examined the internal consistency
      reliability, and factor-based and construct validity of this measure. A back
      translation procedure confirmed that the translation was appropriate, pending a
      minor revision. METHODS: A total of 185 men and 58 women at a manufacturing
      factory in Japan were surveyed using a mailed questionnaire including the OJQ and
      other job stressors. RESULTS: Cronbach alpha coefficients of the two OJQ
      subscales were high (0.85-0.94) for both sexes. The hypothesized two factors
      (i.e., procedural justice and interactional justice) were extracted by the factor
      analysis for men; for women, procedural justice was further split into two
      separate dimensions supporting a three- rather than two-factor structure.
      Convergent validity was supported by expected correlations of the OJQ with job
      control, supervisor support, effort-reward imbalance, and job future ambiguity in
      particular among the men. CONCLUSION: The present study shows that the Japanese
      version of the OJQ has acceptable levels of reliability and validity at least for
      male employees.

PMID- 19096198
TI  - Occupational risk from measles in healthcare personnel: a case report.

PMID- 19096199
TI  - Oral lead exposure induces dysbacteriosis in rats.
AB  - OBJECTIVES: Lead's (Pb(II)) possible role in intestinal pathologies of microbial
      etiology remains mostly unknown. The aim of this study was to examine the effects
      of lead on the gut microbial community and its interactions with rat intestinal
      epithelium. METHODS: The lead-induced changes in different intestinal microbial
      groups (lactose-positive lac(+) and -negative lac(-) E.coli strains, lactobacilli
      and yeasts) were followed separately by the colony-forming unit (CFU) method.
      Samples were taken from outbred white rats subjected to different exposure
      schedules. Additionally, the impact of different lead doses on microbial adhesion
      to cultured intestinal cells (IEC-6) was investigated. Finally, the lead
      accumulation and distribution were measured by means of atomic absorption
      spectrometry. RESULTS: For the first time it was shown that oral lead exposure
      causes drastic changes in the gut microbial community. Proportional to the lead
      dose received, the relative number of lactose-negative E.coli cells increased
      dramatically (up to 1,000-fold) in comparison to the other microbial groups
      during 2 wk of exposure. Considering the number of microbes in the intestine,
      such a shift in intestinal microflora (dysbacteriosis) is very significant.
      Adhesion studies showed certain stimulating effects of lead on E. coli attachment
      to rat intestinal epithelium as compared to Lactobacillus attachment.
      CONCLUSIONS: The mechanisms providing the apparent competitive success of the
      lac(-) group are unclear but could be related to changes in surface interactions
      between microbial and host cells. This study may provide important clues for
      understanding the pathological effects of metal dietary toxins in human beings.

PMID- 19096200
TI  - Do we recover from vacation? Meta-analysis of vacation effects on health and well
      being.
AB  - OBJECTIVES: The aim of this meta-analysis is to investigate to what extent
      vacation has positive effects on health and well-being, how long such effects
      endure after work resumption, and how specific vacation activities and
      experiences affect these relationships. METHODS: Based on a systematic literature
      search (PsycInfo, Medline) and methodological exclusion criteria, in a stepwise
      approach, 7 studies were selected and reviewed. Effect sizes (Cohen's d) were
      calculated i) for every outcome variable within every study, ii) for every study
      by averaging the effect sizes per study, and iii) for homogeneous categories of
      outcome variables (exhaustion, health complaints, life satisfaction). RESULTS:
      The results suggest that vacation has positive effects on health and well-being
      (small effect, d=+0.43), but that these effects soon fade out after work
      resumption (small effect, d=-0.38). Our research further demonstrated that
      vacation activities and experiences have hardly been studied. Therefore, their
      contribution to vacation effect and fade out remains unclear. DISCUSSION:
      Progress in future vacation research will depend on strong research designs that
      incorporate repeated measurements pre-, inter- and post-vacation.

PMID- 19096201
TI  - Neuropeptide urocortin 1 and its receptors are expressed in the human liver.
AB  - The corticotropin-releasing hormone (CRH) system, consisting of CRH, urocortins
      (Ucns), their receptors CRH(1) and CRH(2), and CRH-binding protein, holds the
      principal role in mediating the response to stress stimuli. Besides their
      expression in the brain, CRH neuropeptides and receptors have been found in
      multiple peripheral sites. We investigated the expression of the CRH system in
      the human liver, using RT-PCR and immunohistochemistry. Ucn 1 gene transcripts
      were amplified in all the human liver biopsies examined. Ucn 1 immunoreactivity
      was localized in hepatocytes. CRH(1) and CRH(2(alpha)) receptor gene expression
      was also found, and receptor protein had a similar distribution to Ucn 1.
      Finally, Ucn 1 and CRH receptor expression was demonstrated in hepatic biopsies
      from a variety of liver pathologies, including primary or metastatic liver
      carcinoma and cirrhosis. We conclude that the CRH system is expressed by human
      liver under normal and pathological conditions, Ucn 1 being the major ligand.
      Further study is required to unfold the biological role of these effectors in
      liver physiology and pathogenesis, as they may act in an autocrine manner through
      activation of the CRH receptors expressed locally.

PMID- 19096202
TI  - Effects of ageing on adaptation during vibratory stimulation of the calf and neck
      muscles.
AB  - BACKGROUND: The ability to adapt and habituate based on prior experiences is
      important for human movement control, fall prevention and for the ability to
      enhance performance during various human activities. However, little is known
      about the ability for the elderly to adapt to balance perturbations in the
      lateral direction. OBJECTIVE: To determine whether adaptation, i.e., the ability
      to adjust postural control to handle balance perturbations better over time,
      differed in the elderly subjects compared with young subjects in the
      anteroposterior and lateral directions, and whether the site of the balance
      perturbation or the presence or absence of vision affected the response. METHODS:
      Postural stability was measured as anteroposterior and lateral torque variance in
      a young group (n = 18 (9 female and 9 male), average age = 29.1 years) and an
      elderly group (n = 16 (5 female and 11 male), average age = 71.5 years) with eyes
      open and closed during balance perturbations from calf and neck vibrations. After
      a 30-s period of quiet stance, these vibrations were repeated over a period of
      200 s, so the adaptive responses could be analyzed by splitting the data into 50
      s periods. RESULTS: The adaptive responses in the anteroposterior and lateral
      directions were different. Adaptation in the anteroposterior direction occurred
      to an almost equal extent in the elderly and young, whereas adaptation in the
      lateral direction was markedly larger in the elderly in all tests except for neck
      vibration with eyes closed. Age, vision and vibration site were all influential
      factors for recorded body movements, but no significant combined effects were
      found. CONCLUSION: Balance perturbation instigates an adaptive response in the
      elderly in both the anteroposterior and lateral directions. However, during
      perturbation, age and vision are both very influential factors for the stability,
      thus associating the previously documented age-related decline in visual
      functioning with a higher risk of falls in this age range.

PMID- 19096203
TI  - Marco Fraccaro, 1926-2008.

PMID- 19096204
TI  - Humans and chimpanzees differ in their cellular response to DNA damage and non
      coding sequence elements of DNA repair-associated genes.
AB  - Compared to humans, chimpanzees appear to be less susceptible to many types of
      cancer. Because DNA repair defects lead to accumulation of gene and chromosomal
      mutations, species differences in DNA repair are one plausible explanation. Here
      we analyzed the repair kinetics of human and chimpanzee cells after cisplatin
      treatment and irradiation. Dot blots for the quantification of single-stranded
      (ss) DNA repair intermediates revealed a biphasic response of human and
      chimpanzee lymphoblasts to cisplatin-induced damage. The early phase of DNA
      repair was identical in both species with a peak of ssDNA intermediates at 1 h
      after DNA damage induction. However, the late phase differed between species.
      Human cells showed a second peak of ssDNA intermediates at 6 h, chimpanzee cells
      at 5 h. One of four analyzed DNA repair-associated genes, UBE2A, was
      differentially expressed in human and chimpanzee cells at 5 h after cisplatin
      treatment. Immunofluorescent staining of gammaH2AX foci demonstrated equally high
      numbers of DNA strand breaks in human and chimpanzee cells at 30 min after
      irradiation and equally low numbers at 2 h. However, at 1 h chimpanzee cells had
      significantly less DNA breaks than human cells. Comparative sequence analyses of
      approximately 100 DNA repair-associated genes in human and chimpanzee revealed
      13% and 32% genes, respectively, with evidence for an accelerated evolution in
      promoter regions and introns. This is strikingly contrasting to the 3% of DNA
      repair-associated genes with positive selection in the coding sequence. Compared
      to the rhesus macaque as an outgroup, chimpanzees have a higher accelerated
      evolution in non-coding sequences than humans. The TRF1-interacting, ankyrin
      related ADP-ribose polymerase (TNKS) gene showed an accelerated intraspecific
      evolution among humans. Our results are consistent with the view that chimpanzee
      cells repair different types of DNA damage faster than human cells, whereas the
      overall repair capacity is similar in both species. Genetic differences in non
      coding sequence elements may affect gene regulation in the DNA repair network and
      thus contribute to species differences in DNA repair and cancer susceptibility.

PMID- 19096205
TI  - The karyotype of Alouattapigra (Primates: Platyrrhini): mitotic and meiotic
      analyses.
AB  - We describe for the first time the karyotype of the black howler monkey, Alouatta
      pigra. Conventional staining, G- and C-banding, and fluorescence in situ
      hybridization (FISH) with a peptide nucleic acid (PNA) pantelomeric probe were
      performed. Eight free ranging adult individuals, four males and four females,
      within the natural distribution of the species presented a diploid karyotype with
      2n = 58. Mitotic analyses showed an autosomal complement composed of 6
      submetacentric, 3 metacentric, and 19 acrocentric chromosome pairs for females,
      and 6 submetacentric, 3 metacentric, and 18 acrocentric pairs for males. Meiotic
      analyses in males revealed 27 autosomal bivalents and a quadrivalent composed of
      a submetacentric X(1) and acrocentric X(2), Y(1), and Y(2). The G-banded
      karyotype allowed us to identify pair #17 as the autosomal pair involved in the
      rearrangement and the morphology of the quadrivalent components. C-banding
      technique in metaphase I corroborated the structure of the quadrivalent showing
      four C+ centromeres. FISH analysis showed telomeric signals at the terminal
      regions of all chromosomes. No interstitial signals were detected. DNA sequence
      data were in accordance with those previously published for this species.

PMID- 19096206
TI  - A genome assembly-integrated dog 1 Mb BAC microarray: a cytogenetic resource for
      canine cancer studies and comparative genomic analysis.
AB  - Molecular cytogenetic studies have been instrumental in defining the nature of
      numerical and structural chromosome changes in human cancers, but their
      significance remains to be fully understood. The emergence of high quality genome
      assemblies for several model organisms provides exciting opportunities to develop
      novel genome-integrated molecular cytogenetic resources that now permit a
      comparative approach to evaluating the relevance of tumor-associated chromosome
      aberrations, both within and between species. We have used the dog genome
      sequence assembly to identify a framework panel of 2,097 bacterial artificial
      chromosome (BAC) clones, selected at intervals of approximately one megabase.
      Each clone has been evaluated by multicolor fluorescence in situ hybridization
      (FISH) to confirm its unique cytogenetic location in concordance with its
      reported position in the genome assembly, providing new information on the
      organization of the dog genome. This panel of BAC clones also represents a
      powerful cytogenetic resource with numerous potential applications. We have used
      the clone set to develop a genome-wide microarray for comparative genomic
      hybridization (aCGH) analysis, and demonstrate its application in detection of
      tumor-associated DNA copy number aberrations (CNAs) including single copy
      deletions and amplifications, regional aneuploidy and whole chromosome
      aneuploidy. We also show how individual clones selected from the BAC panel can be
      used as FISH probes in direct evaluation of tumor karyotypes, to verify and
      explore CNAs detected using aCGH analysis. This cytogenetically validated, genome
      integrated BAC clone panel has enormous potential for aiding gene discovery
      through a comparative approach to molecular oncology.

PMID- 19096207
TI  - SNP detection and comparative linkage mapping of 66 bone-related genes in the
      pig.
AB  - Osteoporosis is a multigenic complex disorder. Though the mouse and rat are used
      as experimental models for human osteoporosis, the pig bone remodeling cycle is
      histologically more similar to human than the rat or mouse. Moreover, livestock
      genomics have many advantages over model organisms and human studies for complex
      trait dissection. Hence, in the present work 66 bone-related genes were newly
      genetically mapped on pig chromosomes. Comparative chromosomal patterns of bone
      related genes in the pig, human, mouse and rat provide clues that the chromosomal
      organization of bone-related genes in pigs is more similar to human than that of
      the mouse and rat. Therefore, the pig can be considered as one of the better
      models for studying the molecular genetics of bone-related disorders.

PMID- 19096208
TI  - Karyotype evolution of giraffes (Giraffa camelopardalis) revealed by cross
      species chromosome painting with Chinese muntjac (Muntiacus reevesi) and human
      (Homo sapiens) paints.
AB  - Considering the giraffe (Giraffa camelopardalis, GCA, 2n = 30) as a primitive
      species, its comparative genomic data are critical for our understanding of the
      karyotype evolution of pecorans. Here, we have established genome-wide
      chromosomal homologies between giraffe, Chinese muntjac (Muntiacus reevesi, MRE,
      2n = 46) and human (Homo sapiens, HSA, 2n = 46) with whole sets of chromosome
      specific paints from Chinese muntjac and human, in addition to providing a high
      resolution G-banding karyotype of giraffe. Chinese muntjac and human chromosome
      paints detected 32 and 45 autosomal homologs in the genome of giraffe,
      respectively. Our results suggest that it would require at least thirteen
      fissions, six fusions and three intrachromosomal rearrangements to 'transform'
      the 2n = 44 eutherian ancestral karyotype to the 2n = 58 pecoran ancestral
      karyotype. During giraffe evolution, some ancestral eutherian syntenies (i.e.
      association of HSA3/21, 4/8, 7/16, 14/15, 16/19 and two forms of 12/22) have been
      retained, while several derived syntenies (i.e. associations of human homologous
      segments 2/1, 2/9, 5/19, 4/12/22, 8/9, and 10/20) have been produced. The
      reduction of chromosome number in giraffe from the 2n = 58 pecoran ancestral
      karyotype could be primarily attributed to extensive Robertsonian translocations
      of ancestral chromosomal segments. More complex chromosomal rearrangements
      (including tandem fusion, centromere repositioning and pericentric inversion)
      have happened during the evolution of GCA2 and GCA8.

PMID- 19096209
TI  - Discrimination of 2n = 60 Spalax leucodon cytotypes (Spalacidae, Rodentia) in
      Turkey by means of classical and molecular cytogenetic techniques.
AB  - Comparative studies among seven populations of 2n = 60 S. leucodon employing
      classic cytogenetics (G- bands, C-bands, AgNOR-staining), fluorochrome staining,
      and fluorescence in situ hybridization of telomeric and rDNA probes are reported
      here for the first time. The studied specimens were assigned to two cytotypes: 2n
      = 60W and 2n = 60R. The basic karyotype of both cytotypes consisted of eight
      pairs of subtelocentric and 21 pairs of acrocentric autosomes, subtelocentric X
      and acrocentric Y chromosomes. Both cytotypes had variable numbers of B
      chromosomes (1-3) and variable numbers of autosomal arms (NFa = 74-76) caused by
      amplification (deletion) of heterochromatin short arms in the second pair. The
      short arms of subtelocentric chromosomes were comprised of heterochromatin in
      both cytotypes. Nucleolar organizer regions (NORs) and rDNA clusters were
      detected at telomeric sites of the short arms in pairs Nos. 3, 5, 6, 9, and 13 in
      cytotype W, and in the short arms of pair No. 6, 8, 12, 13, and 16 in cytotype R.
      Different locations of rDNA clusters allowed unambiguous discrimination between
      two S. leucodon cytotypes possessing the same 2n = 60 and similar NFa (74-76)
      variability. Our findings suggest a high level of chromosomal divergence, which
      means that it is possible to consider these cytotypes as a well-differentiated,
      chromosomal lineage within the leucodon group.

PMID- 19096210
TI  - Synteny conservation of the Z chromosome in 14 avian species (11 families)
      supports a role for Z dosage in avian sex determination.
AB  - In order to determine synteny conservation of the avian Z chromosome, a chicken
      (Gallus gallus, GGA) Z chromosome painting probe was hybridized to the
      chromosomes of 14 bird species belonging to 11 different families. The GGAZ
      painted the Z chromosomes in all species analyzed, suggesting strong conservation
      of its gene content among the different avian lineages. This was confirmed by the
      mapping of five GGAZ-orthologous genes (DMRT1, GHR, CHRNB3, ALDOB, B4GALT1) to
      the Z chromosomes of eight other species. The shuffled order of these genes on
      different Z chromosomes can be explained by the prevalence of intrachromosomal
      rearrangements during avian evolution. Synteny conservation of the mammalian X is
      generally thought to be the result of X chromosome inactivation. The absence of Z
      chromosome inactivation implies sex-specific dosage differences of a highly
      conserved array of Z-linked genes in birds. The evolutionary conservation of the
      entire Z chromosome among avian lineages supports the idea that avian sex
      determination and/or sex-specific functions are largely based on sex chromosome
      dosage. We propose that the accumulation of male-specific genes on the Z
      chromosome confers selective pressure on the Z to conserve its synteny.

PMID- 19096211
TI  - Comparative chromosome painting between chicken and spectacled owl (Pulsatrix
      perspicillata): implications for chromosomal evolution in the Strigidae (Aves,
      Strigiformes).
AB  - The spectacled owl (Pulsatrix perspicillata), a species found in the Neotropical
      region, has 76 chromosomes, with a high number of biarmed chromosomes. In order
      to define homologies between Gallus gallus and Pulsatrixperspicillata
      (Strigiformes, Strigidae), we used chromosome painting with chicken DNA probes of
      chromosomes 1-10 and Z and telomeric sequences. This approach allowed a
      comparison between Pulsatrixperspicillata and other species of Strigidae already
      analyzed by chromosome painting (Strix nebulosa and Bubo bubo, both with 2n =
      80). The results show that centric fusions and fissions have occurred in
      different chromosomal pairs and are responsible for the karyotypic variation
      observed in this group. No interstitial telomeric sequences were found. Although
      the largest pair of chromosomes in P. perspicillata and Bubo bubo are
      submetacentric, they are homologous to different chicken chromosomes: GGA1/GGA2
      in P. perspicillata and GGA2/GGA4 in B. bubo.

PMID- 19096212
TI  - Microdissection and whole chromosome painting. Improving sex chromosome analysis
      in Triportheus (Teleostei, Characiformes).
AB  - Triportheus fish species present 2n = 52 chromosomes. The karyotypes show similar
      macrostructure and a ZZ/ZW sex chromosome system, which probably represents
      synapomorphy for the genus. A probe of the Z chromosome was obtained from T.
      nematurus through microdissection, followed by unspecific amplification via DOP
      PCR. This probe was used for WCP (whole chromosome painting) through fluorescent
      in situ hybridization (FISH) in several other Triportheus species, to analyze the
      differentiation of the ZZ/ZW system. The homology between this probe and
      chromosomes of species from other genera, putatively related to Triportheus, was
      also examined to search for evidence about evolution of their sex chromosomes.
      Complete homology was found among the Z chromosomes of all Triportheus species,
      while only small positive signals were found on the W chromosomes. Hybridization
      signals were absent in species from other genera. The present results reinforce
      both the conservative nature of Z chromosomes and the hypothesis that the ZZ/ZW
      sex chromosome system is a synapomorphic feature of Triportheus. On the other
      hand, besides reduction of size, W chromosomes have undergone accentuated
      composition changes in relation to Z chromosomes, since only a small region,
      usually located in the short arm, kept homology with the Z chromosomes.

PMID- 19096213
TI  - XX/XY heteromorphic sex chromosome systems in two bullhead catfish species,
      Liobagrusmarginatus and L. styani (Amblycipitidae, Siluriformes).
AB  - Karyotypes and chromosomal characteristics of two species of bullhead catfish of
      the genus Liobagrus, namely L. marginatus and L. styani were examined by means of
      conventional (Giemsa and CMA(3) staining) and molecular (FISH with telomeric, 5S
      and 18S rDNA probes, respectively) cytogenetic techniques. The diploid numbers of
      L. marginatus and L. styani were 2n = 24 and 30 respectively. The karyotypes
      were: L. marginatus, 20m+2sm+2st in females and 19m+2sm+2st+1a in males; L.
      styani, 16m+ 10sm+4st in both sexes. The karyotypes of the two species and the
      delayed-pairing of synaptonemal complexes in meiosis of L. marginatus suggested
      the presence of heteromorphic XX/XY sex chromosome systems. The results of
      (TTAGGG)(n)FISH and CMA(3)-staining suggested that Robertsonian fusion might play
      an important role in chromosome differentiation among these species of Liobagrus.
      The 5S rDNA situated on the sex chromosomes of L. marginatus and 18S rDNA on the
      sex chromosomes of L. styani were located by FISH, and the origins of
      heteromorphic sex chromosomes via chromosomal reversion or unequal crossing over
      of heterochromatin were hypothesized.

PMID- 19096214
TI  - Chromosome reduction in Eleocharis maculosa (Cyperaceae).
AB  - Chromosome numbers in Cyperaceae lower than the typical basic number x = 5 have
      been described for only three species: Rhynchospora tenuis (n = 2), Fimbristylis
      umbellaris (n = 3) and Eleocharis subarticulata (n = 3). Eleocharis maculosa is
      recorded here as the fourth species of Cyperaceae that has a chromosome number
      lower than 2n = 10, with 2n = 8, 7 and 6. The karyotype differentiation in E.
      maculosa was studied using conventional staining (mitosis and meiosis), FISH with
      45S and 5S rDNA and telomere probes. The results allow us to determine which
      chromosomes of the chromosome race with 2n = 10 fused to form the remaining
      reduced numbers, as well as to understand how the symploidy and translocation
      mechanisms were important in karyotype differentiation and the formation of
      chromosome races in Eleocharis.

PMID- 19096215
TI  - Characterization of 11p14-p12 deletion in WAGR syndrome by array CGH for
      identifying genes contributing to mental retardation and autism.
AB  - WAGR (Wilms tumor, Aniridia, Genitourinary malformations and mental Retardation)
      syndrome is a rare genomic disorder caused by deletion of the 11p14-p12
      chromosome region. The majority of WAGR patients have mental retardation and
      behavioral problems, and more than 20% of the patients also have features of
      autism. While the Wilms tumor/genitourinary anomalies and aniridia are caused by
      deletion of WT1 and PAX6 respectively, the genomic cause of mental retardation
      and autism in WAGR syndrome remains unknown. Using oligonucleotide arrays, we
      have characterized the 11p14-p12 deletions in 31 patients and identified all the
      genes involved in each deletion. The deletions had sizes ranging from 4.9 to 23
      Mb that encompass 18-62 genes (40 on average). In addition to WT1 and PAX6, all
      the patients had deletion of PRRG4 (transmembrane gamma-carboxyglutamic acid
      protein 4). The majority of them had deletion of BDNF (brain-derived neurotrophic
      factor) and SLC1A2 [solute carrier family 1 (glial high affinity glutamate
      transporter) member 2]. Deletion of BDNF and SLC1A2 occurred in patients with
      autism more frequently than in those without autism. Literature review on the
      functions of the genes suggests that haploinsufficiency of SLC1A2, PRRG4, and
      BDNF may contribute to mental retardation and behavioral problems. In particular,
      BDNF may modulate the risk of autism in WAGR patients as suggested by its link
      with Rett syndrome as a target of MECP2. We observed that all the de novo
      deletions occurred in the chromosome 11 inherited from the father in the families
      genotyped, implying a predisposition for de novo mutations occurring in
      spermatogenesis and possible involvement of imprinting in cognitive impairment in
      WAGR patients.

PMID- 19096216
TI  - [Fetal programming].
AB  - The intrauterine environment not only influences fetal well-being and behaviour
      during pregnancy, but also predisposes the fetus in many health aspects of later
      life. The terms 'fetal programming' and 'developmental origins of health and
      disease' reflect the enormous impact of pregnancy-related factors on the
      individual and the health.

PMID- 19096217
TI  - [Fetal growth retardation and diseases in adult life].
AB  - Numerous epidemiologic studies in different populations reveal an association
      between intrauterine growth restriction and the occurrence of arterial
      hypertension, arteriosclerosis, hyperlipidemia, type 2 diabetes mellitus and
      mental diseases later in life. Animal studies confirm these associations to be
      independent from genetic conformation and postpartum influences. However, both
      the mechanisms of intrauterine programming and the critical time of an insult to
      result in fetal problems are unclear. Therefore, the results of large-scale,
      prospective studies are needed before therapeutic interventions during pregnancy
      or post partum to prevent adverse effects of fetal programming are scientifically
      justified.

PMID- 19096218
TI  - [Fetal programming by disturbed intrauterine environment - fundamental mechanisms
      exemplified by the regulation of body weight and metabolism].
AB  - Currently, epidemiological and experimental data indicate that exposures during
      prenatal and perinatal life may have lifelong consequences for the risk of
      developing obesity and metabolic and cardiovascular diseases. In this context,
      observations of the offspring of mothers with gestational diabetes as well as
      studies of children with low birth weight were most influential. This paper
      illustrates the current knowledge about perinatal programming of obesity and
      associated diseases and discusses possible etiopathogenic mechanisms, focussing
      on epidemiological and animal studies of the consequences of exposure to maternal
      diabetes and pre-/neonatal undernutrition. The resultant far-reaching potential
      for primary prevention of chronic diseases as well as the paradigmatic character
      of these hypotheses and observations for the general understanding of health and
      disease are highlighted.

PMID- 19096219
TI  - [Preeclampsia and pregnancy-induced hypertension - diseases determined in the
      uterus?].
AB  - 'Fetal programming' describes the association of alterations of the intrauterine
      fetal environment and the subsequent development of cardiovascular, metabolic and
      endocrine disorders in adult life. It is now commonly accepted that beside these
      so-called lifestyle disorders hypertensive disorders in pregnancy have also an
      intrauterine determination. It is commonly agreed that women born with low birth
      weight do have an elevated risk for the development of hyper-tensive pregnancy
      disorders, which is pronounced especially in those women born with low birth
      weight, who become obese in later life. Until now the exact pathophysiological
      mechanisms remain elusive: beside placental mechanisms intrauterine alterations
      in kidney development and insulin resistance seem to be major key factors. The
      pathophysiological similarities and risks of hypertensive pregnancy disorders
      (especially preeclampsia) and these 'lifestyle disorders' - both are also
      considered to be mutual risk factors for the development of the other disorder -
      suggest the possibility of a general impairment of the maternal cardiovascular
      system by intrauterine factors.

PMID- 19096220
TI  - [Reproductive techniques and concepts of psychosomatic medicine].
AB  - OBJECTIVE: The objective of this study was to assess the expectations of the
      patients regarding prenatal examination and assisted reproductive treatment.
      METHODS: The first sample included patients and their partners at the
      commencement of assisted reproductive treatment. The couples were asked to
      predict the success of in vitro fertilization on a scale ranging from 0 to 100%.
      The second sample included pregnant women and their partners prior to prenatal
      examination (level III). These couples were asked what expectations they had
      regarding the prenatal examination. RESULTS: On average, 57% of the women and 61%
      of their partners expected a successful pregnancy in the course of the ongoing
      reproductive treatment. The expectations at the prenatal examination indicated
      that both the women and their partners wished, in the first instance, a
      reassuring outcome and a positive diagnosis of pregnancy. Lower down the scale in
      third and fourth position were safety and assurance. DISCUSSION: The patients
      focused their expectations mainly on the technical possibilities of the
      reproductive techniques. It is therefore necessary in psychosomatic medicine to
      introduce personal concepts for discussion in order to avoid being subordinated
      to prevalent facts.

PMID- 19096221
TI  - [Family and career planning in young physicians].
AB  - OBJECTIVES: The study investigates in what way physicians integrate their desire
      to have children into their career planning. METHODS: Within the framework of a
      prospective cohort study of Swiss medical school graduates on career development
      of young physicians, beginning in 2001, 534 participants (285 women, 249 men)
      were assessed in January 2007, in terms of having children, planning to have
      children, the career aspired to and the work-family balance used or planned.
      RESULTS: Among the study participants, 19% (54) of the women and 24% (59) of the
      men have children. Of the others 88% plan to start a family in the future. Female
      physicians with children are less advanced in their careers than women without
      children; for male physicians no such difference can be observed. Of the female
      physicians with children or the desire for children 42% aspire to work in a
      practice, 28% to a clinical and only 4% to an academic career. Of the male
      physicians with children or the desire for children one third aspire to work in a
      practice, one third to a clinical and 14% to an academic career. The preferred
      model of work repartition of female physicians with children is father full
      time/mother part time or both parents part time; the preferred model of male
      physicians is father full time/mother part time or not working. CONCLUSION:
      Children are an important factor in the career and life planning of physicians,
      female physicians paying more attention to an even work-family balance than male
      physicians.

PMID- 19096222
TI  - [Umbilical cord blood donation: relevant facts. Experts letter Nr. 24 from 24
      from 21 October 2007 (supersedes experts letter Nr. 10 from January, 2002]].

PMID- 19096223
TI  - Erythropoietin prevents diabetes-induced podocyte damage.
AB  - OBJECTIVE: Erythropoietin (EPO) has cytoprotective effects apart from its
      hematopoietic effects. We studied the effects of different EPO molecules on
      podocyte signaling in vitro and on podocyte survival in an experimental model of
      diabetic kidney injury (db/db mouse). METHODS: We elucidated intracellular
      signaling by epoetin-beta, darbepoetin-alpha, and the continuous erythropoietin
      receptor activator (CERA) in immortalized murine podocyte cultures. Moreover, we
      treated db/db mice with placebo or with CERA in a chronic (14-week) randomized
      controlled study. We also studied non-diabetic db/m mice as controls. RESULTS: We
      could clearly demonstrate phosphorylation of the JAK/PI3K pathway and Akt
      signaling in podocytes by epoetin-beta, darbepoetin-alpha and CERA. In the long
      term animal study we found significantly reduced podocyte numbers in placebo
      treated db/db mice compared to db/m control mice (7.4 +/- 0.2 vs. 10.2 +/- 0.9
      per glomerular field; p < 0.05). Chronic CERA treatment ameliorated podocyte loss
      in kidneys of diabetic animals (8.5 +/- 0.5 per glomerular field; p < 0.05 vs.
      placebo-treated db/db mice). CONCLUSION: EPO activates pro-survival intracellular
      pathways in podocytes in vitro, and ameliorates diabetes-induced podocyte loss in
      vivo. Chronic EPO administration may be a feasible way to protect podocyte from
      diabetic injury.

PMID- 19096224
TI  - Patterns of influenza vaccination among stroke survivors.
AB  - BACKGROUND: Influenza remains a leading cause of vaccine-preventable death in the
      USA. Vaccination rates in the eligible general population are well below targets,
      and rates in stroke survivors are unknown. METHODS: We assessed the prevalence
      and independent predictors of influenza vaccination among stroke survivors using
      the National Health Interview Survey (NHIS) 2006 survey. RESULTS: There were a
      total of 706 self-reported strokes (3%) out of a total of 24,275 adults
      completing the survey (mean age 67 +/- 15 years). The prevalence of influenza
      vaccination over the previous year among stroke survivors was 54.3%. Factors
      independently associated with vaccination were increasing age (odds ratio = 1.04
      per year, 95% CI: 1.02-1.06), Black race (odds ratio = 0.52, 95% CI: 0.33-0.82
      compared to white race), and health insurance coverage (odds ratio = 3.5, 95% CI:
      1.37-9.05). CONCLUSIONS: In 2006, only about half the stroke survivors in the USA
      received influenza vaccinations, leaving substantial room for improvement.
      Targeting stroke survivors in minority groups or without health insurance
      coverage may help bridge this gap.

PMID- 19096225
TI  - Prevalence of possible idiopathic normal-pressure hydrocephalus in Japan: the
      Osaki-Tajiri project.
AB  - BACKGROUND: Several studies have reported that the prevalence of idiopathic
      normal-pressure hydrocephalus (iNPH) was between 0 and 5%. However, the precise
      prevalence in a community-based elderly population remains unclear. We
      investigated the prevalence of possible iNPH retrospectively using an age- and
      gender-stratified random sample database. METHODS: Five hundred and sixty-seven
      participants were randomly selected from among the 1,654 members of the
      population aged 65 years and older in Tajiri, Japan, and 497 underwent MRI. We
      classified participants as having possible iNPH if they had: (1) ventricular
      enlargement, as shown by an Evans index of > or = 0.3, with closing sulci at the
      high convexity with dilation of the sylvian fissure on MRI, (2) at least one of
      the iNPH clinical triad (gait disturbance, urinary incontinence and cognitive
      impairment), and (3) no identifiable potential secondary cause of hydrocephalus.
      RESULTS: We found 7 participants who met the criteria mentioned above. Cognitive
      impairments were the most common symptoms (n = 6) followed by gait disturbances
      (n = 3); however, urinary incontinence was not observed. No full clinical triad
      was present in the patients and only 3 participants had 2 of the triad.
      CONCLUSIONS: We considered the prevalence of possible iNPH in elderly adults to
      be 1.4% (95% confidence interval = 0.6-2.9%).

PMID- 19096226
TI  - Transparency of information on eye diseases on the internet.
AB  - BACKGROUND: Transparency is an indicator of trustworthiness and quality of health
      information about eye diseases on the Internet. METHODS: 20 websites that
      contained information about eye diseases aimed at the general public were
      evaluated. A modified Afgis (Aktionsforum Gesundheitsinformationssystem/action
      forum health information system) project transparency checklist was used.
      RESULTS: On average, 6.15 +/- 1.68 criteria were fulfilled. All websites
      maintained separation between advertising and editorial content. Between 80 and
      90% of the websites studied contained complete information about the provider,
      aims and target audience, and feedback from users. The criteria for privacy were
      met by 70% of websites, 40% met those for currency of content and data, 35% those
      for methods of quality assurance, 15% those for financing and sponsoring and 0%
      met the requirements for authors and sources of information. CONCLUSION: Visually
      impaired people benefit from transparency, because this facilitates accessibility
      to web-based health information. Hence, websites containing health information
      related to eye diseases should meet the demands of transparency.

PMID- 19096227
TI  - Why might people donate tissue for cancer research? Insights from
      organ/tissue/blood donation and clinical research.
AB  - Little is known about why patients with cancer do or do not donate their
      biopsied/cancerous tissue to research. A review of the literature on motivations
      to participate in clinical research and to donate tissues/organs for therapeutic
      use may provide some insights relevant to tumour banking research. While more
      research is necessary, a better understanding of the factors that motivate
      patients to give or refuse consent to tumour banking may ultimately improve
      consent practices, public trust and donation rates.

PMID- 19096228
TI  - Effect of hypoxic-ischemic injury on serine palmitoyltransferase activity in the
      developing rat brain.
AB  - BACKGROUND: Sphingolipid metabolism is strongly associated with central nervous
      system myelination. Ceramide is the most active of the sphingolipid metabolites.
      On the basis of ceramide biosynthesis indicated by serine palmitoyltransferase
      activity and cerebroside generated by ceramide, the evaluation of serine
      palmitoyltransferase activity in developing brains or hypoxic-ischemic damaged
      brains is worthwhile. METHODS: Using a scintillation counter, we assessed serine
      palmitoyltransferase activity, a rate-limiting enzyme of sphingolipid metabolism,
      in the brains of developing rats and compared the activity with hypoxic-ischemic
      brains, using the method of Rice on postnatal day 7 (P7). RESULTS: In the control
      groups, serine palmitoyltransferase activity was detected in the microsomal
      fraction of whole brain homogenates from P4, which was earlier than the initial
      expression of myelin-specific proteins such as myelin basic protein and
      proteolipid protein on immunochemistry. Serine palmitoyltransferase activity
      increased along with development on P8, P10, P14 and P21. However, hypoxic
      ischemic brains showed lower serine palmitoyltransferase activity than control
      brains on P8, P10, P14 and P21. CONCLUSIONS: These results suggest that increase
      in serine palmitoyltransferase activity before myelin-specific protein expression
      may be an initial step in myelinogenesis and a decline in serine
      palmitoyltransferase activity in hypoxic-ischemic brains may be one of the major
      causes of delayed myelination.

PMID- 19096229
TI  - Expression of angiogenesis-related genes regulates different steps in the process
      of tumor growth and metastasis in human urothelial cell carcinoma of the urinary
      bladder.
AB  - OBJECTIVE: This study was designed to determine the relative activity of
      angiogenesis-related genes in the regulation of tumorigenicity and subsequent
      metastases of urothelial cell carcinomas (UC) of the urinary bladder. METHODS: We
      selected the clones with the highest and lowest expression level of basic
      fibroblast growth factor (bFGF), vascular endothelial growth factor
      (VEGF)/vascular permeability factor or interleukin-8 (IL-8) in the highly
      tumorigenic and metastatic human UC cell line 253J B-V. Tumorigenicity and
      production of spontaneous lymph node metastases were evaluated 1, 2, 4, 8 and 12
      weeks after orthotopic implantation of each specific expression clone into the
      urinary bladder of athymic nude mice. Moreover, the transitional changes in the
      expression of angiogenesis-related genes and neovascularization were determined
      in tumors and metastases. RESULTS: At the early stage of tumor growth following
      orthotopic implantation, tumorigenicity and metastases were significantly
      increased in the clones with the highest expression of bFGF and IL-8, while they
      were significantly inhibited in the clones with the lowest expression of bFGF and
      IL-8 compared to parental 253J B-V. In the tumors, specific expression of
      angiogenesis-related genes and intratumor neovascularity of each clone were
      gradually regulated to the same level as parental 253J B-V. In metastasized
      tumors of the highest and lowest IL-8-expressing clones, IL-8 expression was
      consistently high and low, respectively. CONCLUSIONS: These findings indicate
      that at the early stage of tumor growth, bFGF and IL-8 expression play important
      roles in the regulation of angiogenesis, tumorigenicity and subsequent metastases
      of human bladder cancer.

PMID- 19096230
TI  - Specific induction of tumor neovasculature death by modified murine PPE-1
      promoter armed with HSV-TK.
AB  - BACKGROUND: One strategy to increase tissue specificity of gene therapy is to use
      promoters or enhancers. OBJECTIVES: (1) To enhance the selectivity of a murine
      preproendothelin-1 (PPE-1) promoter in tumor angiogenesis by using a positive
      endothelial transcription-binding element. (2) To test the specificity and
      efficiency of the modified PPE-1 promoter [PPE-1(3X)] in vitro and in vivo by
      using reporter genes, and the therapeutic gene herpes simplex virus-thymidine
      kinase (HSV-TK) in a mouse model of Lewis lung carcinoma (LLC). RESULTS: The
      modified PPE-1 promoter specifically induced expression in the tumor angiogenic
      vascular bed with a 35-fold higher expression compared to the normal vasculare
      bed of the lung. Thus, when the HSV-TK gene controlled by the modified PPE-1
      promoter was used systemically, it induced tumor-specific necrosis, apoptosis and
      mononuclear infiltrates, leading to massive destruction of the neovasculature of
      the pulmonary metastasis, which suppressed metastasis development. CONCLUSIONS:
      These results show that an adenoviral vector armed with HSV-TK controlled by the
      endothelial-selective murine PPE-1(3X) promoter is efficient and safe to target
      tumor neovasculature.

PMID- 19096231
TI  - Susceptibility of XRCC3, XPD, and XPG genetic variants to cervical carcinoma.
AB  - OBJECTIVE: DNA repair genes play a key role in maintaining genomic stability and
      integrity. DNA repair gene polymorphisms, such as those of XRCC3 and xeroderma
      pigmentosum, complementation group D and G (XPD, XPG), contribute to
      carcinogenesis. In this study, we investigated the correlation between cervical
      carcinoma risk and XRCC3, XPD, XPG genetic variants. METHODS: A case-control
      study of 400 cases including 200 carcinoma, 200 cervical intraepithelial
      neoplasia (CIN) and 200 normal women was performed. Four single nucleotide
      polymorphisms (SNPs) (XRCC3 Thr241Met, XPG His1104Asp, XPD Asp312Asn, and XPD
      Lys751Gln) were genotyped by mismatch amplification polymerase chain reaction.
      RESULTS: Women carrying homozygous Asp1104Asp genotypes had a significantly
      decreased risk of cervical or cervical squamous cell carcinoma compared to
      His1104Asp or His1104His genotypes. Similarly, XPD Asn312Asn (AA) reduced the
      risk of cervical or cervical squamous cell carcinoma. No association of XRCC3
      Thr241Met or XPD Lys751Gln and cervical carcinoma was found. None of the 4 SNPs
      influenced the risk of CIN in our study. CONCLUSION: Our results support the
      hypothesis that genetic variations in DNA repair genes may contribute to an
      inherited genetic susceptibility to cervical carcinoma.

PMID- 19096232
TI  - Immunohistochemical analysis of cell cycle-related molecules in gastric
      carcinoma: prognostic significance, correlation with clinicopathological
      parameters, proliferation and apoptosis.
AB  - OBJECTIVE: We aimed to investigate the biological significance of cell cycle
      regulators in gastric carcinoma. METHODS: Immunohistochemistry and TUNEL staining
      were performed on tissue array slides containing 293 gastric carcinoma specimens.
      The relationship between the protein expression of each of the cell cycle
      regulators and prognosis, clinicopathological features, proliferation, or
      apoptosis was evaluated. RESULTS: The nuclear immunoreactivity for cyclin D1,
      cyclin E, p21, and p27 was observed in 22, 14, 31 and 27% of cases, respectively.
      The expression of cyclin D1, p21, or p27 positively correlated with early pTNM
      stages, tumor cell proliferation (represented by Ki-67 labeling) and good
      prognosis, whereas it inversely correlated with the lymph node metastasis (p <
      0.05). On the other hand, p27 expression inversely correlated with the apoptosis
      index represented by TUNEL staining (p < 0.001). In addition, the expression of
      cyclin D1 positively correlated with that of p21 or p27 (p < 0.05). CONCLUSIONS:
      Our results showed that the expression of cyclin D1, p21 and p27, alone or in
      combination, are early events in gastric tumorigenesis and may serve as a
      candidate molecular marker for the early gastric carcinoma.

PMID- 19096233
TI  - Antioxidant activity of bisabolol: inhibitory effects on chemiluminescence of
      human neutrophil bursts and cell-free systems.
AB  - Human polymorphonuclear neutrophils (PMN), reactive oxygen species (ROS) and
      inflammatory reactions are closely interrelated, and increasing attention is
      being given to the search for new synthetic or natural antioxidant agents,
      capable of reducing ROS and consequent inflammation. It has been claimed that
      bisabolol (a monocyclic sesquiterpene alcohol) has an antioxidant/anti
      inflammatory activity, but this has almost exclusively been investigated using
      chemical or biochemical tests. We studied the ability of bisabolol to interfere
      with ROS production (luminol-amplified chemiluminescence, LACL) during human PMN
      respiratory bursts induced by both corpusculate(Candida albicans)and soluble
      stimulants (N-formyl-methionyl-leucyl-phenylalanine, fMLP). LACL was also used to
      test cell-free systems (SIN-1 and H2O2/HOCl(-) systems) in order to investigate
      the presence of scavenging activity. After C. albicans stimulation, significant
      concentration-dependent LACL inhibition was observed at bisabolol concentrations
      ranging from 7.7 to 31 microg/ml; after the fMLP stimulus, significant LACL
      inhibition was observed at bisabolol concentrations ranging from 3.8 to 31
      microg/ml. A similar effect was observed in the SIN-1 and H2O2/HOCl(-) systems.
      These findings draw the attention to the possible medical use of bisabolol as a
      means of improving the antioxidant network and restoring the redox balance by
      antagonising oxidative stress.

PMID- 19096234
TI  - Contribution of transient receptor potential vanilloid subtype 1 to the analgesic
      and antihyperalgesic activity of nefopam in rodents.
AB  - In order to further elucidate the mechanism(s) of action of analgesic and
      antihyperalgesic nefopam, its interactions with the transient receptor potential
      vanilloid subtype 1 (TRPV1) were investigated. In sensory neurons of rat embryos,
      dorsal root ganglion (DRG) in culture, nefopam (3-30 mumol/l) and capsazepine
      (TRPV1 antagonist, 10 mumol/l) prevented intracellular calcium elevation and
      calcitonin gene-related peptide release induced by vanilloid agonist capsaicin.
      Unlike nefopam, capsazepine failed to inhibit these same responses induced by KCl
      excess. In vivo, nefopam (0.5 and 2 mg/kg, i.v.) and capsazepine (40 mg/kg, i.p.)
      reduced the licking response due to intraplantar injection of capsaicin in mice.
      These findings suggest that nefopam exerts its analgesic and antihyperalgesic
      effects through multiple mechanisms including blockade of TRPV1 in addition to
      voltage-dependent calcium channels in the DRG.

PMID- 19096235
TI  - Suture fixation technique for a single-piece foldable closed-loop intraocular
      lens.
AB  - PURPOSE: We describe a suture fixation technique for a single-piece foldable
      acrylic closed-loop intraocular lens (IOL) (C-flex, Rayner). METHODS: In our
      experimental model analyzing the stability of acrylic haptics, we confirmed that
      the IOL could be in counterpoise without tilt using only a two-point fixation.
      This new surgical technique was performed in seven patients. RESULTS: The unique
      haptic design allows easy and secure suture fixation. The clinical outcomes were
      encouraging. CONCLUSIONS: It is conceivable that better stabilization can be
      achieved by the broad arc of distal haptic-tissue contact, in addition to suture
      fixation, using our surgical technique with the C-flex IOL.

PMID- 19096236
TI  - Comparison of internal and total optical aberrations for 2 aberrometers: iTrace
      and OPD scan.
AB  - PURPOSE: To compare and evaluate the total and internal aberrations measured by
      two aberrometers: the laser ray tracing aberrometer (iTrace, Tracey Technology)
      and the automatic retinoscope aberrometer (OPD Scan, Nidek). METHODS: A total of
      54 healthy eyes were enrolled in the study. Following pupil dilation, aberrations
      were measured with the iTrace and OPD Scan. We compared the aberrations obtained
      from measurements obtained at pupillary diameters of 4 mm and 6 mm with the OPD
      Scan and iTrace. Aberrations of internal optics and total aberrations were
      compared for the two aberrometers. For each aberrometer and each eye, the
      averaged Zernike data were used to calculate various root-mean-square (RMS) data.
      These parameters, together with the refractive parameters, were then analyzed and
      complimented by paired t-tests. RESULTS: At a pupil diameter of 4 mm, the number
      of total aberrations in the entire eye showed significant differences for the
      mean values of spherical aberrations (Z4,0) obtained with the OPD Scan and iTrace
      aberrometers (p=0.001). Aberrations of the internal optics showed significant
      differences in the mean values of total RMS, coma (Z3,-1), and trefoil (Z3,3)
      between the iTrace and OPD Scan (p<0.001, p=0.01, p<0.001) for the same pupil
      diameter of 4 mm. At a pupil diameter of 6 mm, the two instruments showed a
      similar number of total aberrations. Aberrations of the internal optics showed
      significant differences in the mean values of total RMS, spherical aberration
      (Z4,0), and coma (Z3,-1) between the two devices (p<0.001, p=0.01, p<0.001).
      CONCLUSIONS: The iTrace and OPD Scan showed the largest number of differences for
      aberrations of internal optics rather than total aberrations for both pupil
      diameters. These results suggest that in healthy eyes, the two aberrometers may
      vary in some details. The aberrometers showed more agreement at a pupil diameter
      of 6 mm compared to 4 mm.

PMID- 19096237
TI  - Prediction of refractive error in combined vitrectomy and cataract surgery with
      one-piece acrylic intraocular lens.
AB  - PURPOSE: To compare the predicted and actual refractive errors of hydrophilic,
      one-piece, C-flex 570C (C-flex) intraocular lens (IOL) implantation in
      simultaneous vitrectomy and lens extraction in various conditions. METHODS: One
      hundred fifty-nine eyes of patients who had lens extraction between March 2004
      and September 2005 were enrolled in a retrospective study. Group 1 had lens
      extraction and IOL implantation, and Group 2 had lens extraction and IOL
      implantation with vitrectomy. IOL calculation was done with axial length and
      keratometry measurements. The actual and predicted refractive errors were
      compared at 1 and 6 months postoperatively. The factors influencing the
      postoperative refractive outcomes were analyzed. RESULTS: The mean refractive
      predictive error (i.e., the actual minus predicted spherical equivalent) was
      +0.19+/-0.39 D (Diopter) and -0.26+/-0.45 D at 1 and 6 months postoperatively
      (all: p<0.001) in group 1, and -0.22+/-0.39 D and -0.06+/-0.62 D at 1 and 6
      months postoperatively (p=0.013, p=0.399 respectively). In group 2, all surgical
      factors related to refractive errors were not statistically significant (all:
      p>0.05). CONCLUSIONS: Refractive errors in combined surgery showed myopic shift
      of -0.50 D and -0.32 D at 1 and 6 months postoperatively compared with C-flex IOL
      implantation alone. With the hyperopic tendency of IOL and myopic tendency of
      vitrectomy, the combined surgery made postoperative refractive errors near
      emmetropia.

PMID- 19096238
TI  - Development of toxic anterior segment syndrome immediately after uneventful phaco
      surgery.
AB  - PURPOSE: We report on 15 cases of suspected toxic anterior segment syndrome after
      uneventful phaco surgery. METHODS: We retrospectively reviewed the charts of
      patients who had developed toxic anterior segment syndrome (TASS) after
      uneventful phacoemulsification for senile cataracts between April and December of
      2005. Clinical features and all possible causes were investigated including
      irrigating solutions or drugs, surgical instruments or intraocular lenses,
      sterilization techniques for instruments, or any other accompanying disease.
      RESULTS: The patients consisted of 2 males and 13 females with an average age of
      64.7+/-10.9 years. Five different surgeons had performed their phaco surgeries.
      No abnormal preoperative or operative findings were reported. Nevertheless, all
      15 patients developed a moderate degree of corneal edema. Ordinary treatments
      were not helpful. We suspect that lack of sterilization resulted in the
      development of the syndrome, because after ethylene oxide gas sterilization was
      replaced with autoclaving, no such incidents have occurred. CONCLUSIONS: Toxic
      anterior segment syndrome requires special attention and thorough management,
      including sterilization of reused surgical instruments.

PMID- 19096239
TI  - Clinical efficacy and complications of intraocular lens exchange for opacified
      intraocular lenses.
AB  - PURPOSE: To evaluate the clinical efficacy and complications of intraocular lens
      (IOL) exchange. METHODS: A review of medical records was performed for 52 eyes
      that had undergone an IOL exchange due to IOL opacification. Surgical
      complications and their incidences were analyzed. The mean best corrected visual
      acuity (BCVA) after the IOL exchange was compared with the mean pre-exchange BCVA
      and with the mean BCVA after the initial IOL implantation. Prediction error of
      refraction and biometric data obtained for the IOL exchange were, if available,
      compared with those obtained for the initial IOL implantation. The prediction
      error for the IOL exchange, calculated from the biometric data obtained before
      the IOL exchange, was compared with that calculated from the measurements
      obtained before the initial IOL implantation. RESULTS: The overall complication
      rates were low and no serious complications were found. The mean BCVA improved
      significantly after the IOL exchange and was not significantly different from
      that obtained after the initial IOL implantation. However, the refractive
      prediction for the IOL exchange was not as good as it was for the initial IOL
      implantation, which was thought to be related with difficulties in axial length
      (AL) measurements. Biometric data taken before the initial IOL implantation was
      associated with a significantly better refractive prediction than those taken
      before the IOL exchange. CONCLUSIONS: IOL exchange was both efficacious and safe
      for visual recovery. However, IOL exchange was related with increased difficulty
      of predicting postoperative refraction; difficulties in AL measurements are the
      suggested cause.

PMID- 19096240
TI  - Comparison of OCT and HRT findings among normal, normal tension glaucoma, and
      high tension glaucoma.
AB  - PURPOSE: To evaluate the relationship between optic disc and retinal nerve fiber
      layer (RNFL) measurements obtained with the optical coherence tomography (OCT)
      and the Heidelberg retina topography (HRT) in normal, normal tension glaucoma
      (NTG), and high tension glaucoma (HTG). METHODS: Normal, NTG and HTG subjects who
      met inclusion and exclusion criteria were evaluated retrospectively. One hundred
      seventy eyes of 170 patients (30 normal, 40 NTG, and 100 HTG) were enrolled.
      Complete ophthalmologic examination, HRT, OCT, and automated perimetry were
      evaluated. RESULTS: Disc area, cup area and cup/disc area ratio measured with HRT
      were significantly different between NTG and HTG (all p < 0.05). Mean RNFL
      thickness measured by OCT with ascanning diameter of 3.4 mm was larger in NTG
      than HTG (84.97+/-24.20 micrometer vs. 73.53+/-27.17 micrometer, p = 0.037). Four
      quadrant RNFL thickness measurements were not significantly different between NTG
      and HTG (all p > 0.05). Mean deviation and corrected pattern standard deviation
      measured by automated perimetry was significantly correlated with mean and
      inferior RNFL thickness in both NTG and HTG (Pearson's r, p < 0.05). Mean RNFL
      thickness/disc area ratio was significantly larger in HTG than NTG (35.21+/-18.92
      vs. 31.30+/-10.91, p = 0.004). CONCLUSIONS: These findings suggest that optic
      disc and RNFL damage pattern in NTG may be different from those of HTG.

PMID- 19096241
TI  - Anterior chamber measurements by pentacam and AS-OCT in eyes with normal open
      angles.
AB  - PURPOSE: To assess the reproducibility and agreement of anterior chamber
      measurements between the Pentacam (PTC) and the Anterior segment optical
      coherence tomography (AOCT) in normal healthy eyes with open angle. METHODS:
      Prospective cross-sectional comparative case series. A total of 162 eyes of 81
      healthy volunteers with normal open angle were included in this study. Anterior
      chamber angle (ACA) and anterior chamber depth (ACD) were measured with PTC and
      AOCT. Intra-observer variability and inter-methods agreement of both instruments
      for ACA and ACD were evaluated. RESULTS: Values of temporal and nasal ACA
      measured by two instruments were similar, and the results of ACD were also not
      significantly different between modalities (p > 0.01). ACA and ACD measurements
      by PTC and AOCT showed good intra-observer and inter-method agreements (all >
      0.9). CONCLUSIONS: PTC and AOCT are presumed to be very useful for the anterior
      chamber angle examination. They may provide good images and quantitative data
      about the angle structures including ACA and ACD.

PMID- 19096242
TI  - Effect of muscle relaxants on short-term results of exotropia surgery: a focus on
      resection procedures.
AB  - PURPOSE: We investigated the effect of muscle relaxants (atracurium) on the
      outcomes of intermittent exotropia surgery under general anesthesia, with a focus
      on resection procedures. METHODS: Thirty four patients who underwent recession
      and resection (R&R) were divided into two groups: atracurium usage (group A,
      n=18) and no atracurium usage (group B, n=16). Patients were divided into two
      subgroups according to the amount of resection of the medial rectus (MR): less
      than 5 mm (group 1, n=13) or 5 mm and greater (group 2, n=21). Deviation angles
      were compared between groups and subgroups. Surgical outcome was defined as
      successful if distant deviation angles were equal to or less than 10 prism
      diopters. RESULTS: The overall postoperative deviation angles did not show
      statistically significant differences between groups A and B. However, in
      patients with larger MR resections (> or = 5 mm), the 1 week postoperative
      distant deviation was significantly larger in group A (1.8+/-2.6 PD) than in
      group B (-1.6+/-4.6 PD, p=0.048 by t-test). The overall undercorrection rate at 3
      months postoperatively for group A was 16.7%, which was higher than that of group
      B (6.3%), and the difference was even larger in subgroups with larger MR
      resections (> or = 5 mm): 18.2% in group A and 0% in group B. CONCLUSIONS:
      Patients who underwent R&R procedures under general anesthesia with a muscle
      relaxant tended to be less corrected than those without muscle relaxant,
      especially in the early postoperative period and with a larger MR resection equal
      to or greater than 5 mm. However, there was no significant difference in the
      later postoperative period.

PMID- 19096243
TI  - Pattern visual evoked potential as a predictor of occlusion therapy for
      amblyopia.
AB  - PURPOSE: This study was conducted to investigate the role of the pattern visual
      evoked potential (pVEP) as a predictor of occlusion therapy for patients with
      strabismic, anisometropic, and isometropic amblyopia. The secondary aim was to
      compare the characteristics of pVEP between strabismic and anisometropic
      amblyopia. METHODS: This retrospective comparative case series included 120
      patients who had received occlusion therapy or a glasses prescription for
      correction of strabismic, anisometropic, and isometropic amblyopia (20 patients
      had strabismic amblyopia, 41 patients had anisometropic amblyopia, and 59
      patients had isometropic amblyopia). For each patient, the value of the P100
      latency on pVEP at the time of the initial diagnosis of amblyopia was collected.
      Subsequently, the P100 latency was compared according to types of amblyopia.
      Fifty of 120 patients (7 patients with strabismic amblyopia, 21 patients with
      anisometropic amblyopia, and 22 patients with isometropic amblyopia) who were
      followed-up for longer than 6 months were divided into two groups based on the
      value of their P100 latency (Group 1, P100 latency 120 msec or less; Group 2,
      P100 latency longer than 120 msec.) The amount of visual improvement after
      occlusion therapy or glasses was compared between two study groups. RESULTS: The
      mean P100 latency was 119.7+/-25.2 msec in eyes with strabismic amblyopia and
      111.9+/-17.8 msec in eyes with non-strabismic (anisometropic or isometropic)
      amblyopia (p=0.213). In Group 1, the mean visual improvement after occlusion
      therapy or glasses was 3.69+/-2.14 lines on Dr. Hahn's standard test chart; in
      Group 2, the mean improvement was 2.27+/-2.21 lines (p=0.023). CONCLUSIONS: The
      P100 latency on pVEP at the time of initial diagnosis was significantly related
      to the visual improvement after occlusion therapy or glasses in patients with
      strabismic, anisometropic, and isometropic amblyopia. Therefore, it was presumed
      that patients with a delayed P100 latency might have less visual improvement
      after occlusion therapy or glasses. In addition, there was no apparent difference
      in P100 latency between patients with strabismic and non-strabismic
      (anisometropic or isometropic) amblyopia.

PMID- 19096244
TI  - Upper eyelid retraction after periorbital trauma.
AB  - We report four unusual cases of upper eyelid retraction following periorbital
      trauma. Four previously healthy patients were evaluated for unilateral upper
      eyelid retraction following periorbital trauma. A 31-year-old man (Case 1) and a
      24-year-old man (Case 2) presented with left upper eyelid retraction which
      developed after blow-out fractures, a 44-year-old woman (Case 3) presented with
      left upper eyelid retraction secondary to a periorbital contusion that occurred
      one week prior, and a 56-year-old man (Case 4) presented with left upper eyelid
      retraction that developed 1 month after a lower canalicular laceration was
      sustained during a traffic accident. The authors performed a thyroid function
      test and orbital computed tomography (CT) in all cases. Thyroid function was
      normal in all patients, CT showed an adhesion of the superior rectus muscle and
      superior oblique muscle in the first case and diffuse thickening of the superior
      rectus muscle and levator complex in the third case. CT showed no specific
      findings in the second or fourth cases. Upper eyelid retraction due to superior
      complex adhesion can be considered one of the complications of periorbital
      trauma.

PMID- 19096245
TI  - A case of epithelial inclusion cyst of iris.
AB  - To report on an epithelial inclusion cyst of the iris that was successfully
      treated with needle aspiration and Ab externo laser photocoagulation. A 6-year
      old boy was treated for a 6.0 mm fluid-filled cyst in the anterior chamber of the
      right eye. Thirteen months previously, he had undergone primary closure of a 6 mm
      full-thickness corneal laceration. The subsequent cyst was diagnosed as an
      epithelial inclusion cyst of the iris. His vision decreased to finger-count at 30
      cm as the cyst grew over the pupil. We performed needle aspiration of the cyst
      and Ab externo laser photocoagulation of the cyst wall. The treated lesion was
      completely removed. The patient's visual acuity recovered to 20/40 without
      complications. There was no recurrence as determined by slit lamp examination up
      to 6 months after treatment. Needle aspiration and Ab externo laser
      photocoagulation can be used to effectively treat epithelial inclusion cysts of
      the iris.

PMID- 19096246
TI  - Ophthalmologic findings of Boucher-Neuhauser syndrome.
AB  - To report a case of Boucher-Neuhauser syndrome, which is an autosomal recessive
      disorder characterized by the triad of spinocerebellar ataxia, chorioretinal
      dystrophy, and hypogonadotropic hypogonadism. An 18-year-old man was seen for
      visual problems, which had been diagnosed as retinitis pigmentosa at the age of
      12 years. His puberty was delayed. At 16 years of age, the patient experienced
      progressive deterioration of his balance and gait disturbance. Then he was
      referred to our clinic because Boucher-Neuhauser syndrome was suspected. He had
      no specific family history; his visual acuity was 0.04 in both eyes. We observed
      broad retinal pigment epithelium atrophy and degeneration in both fundi. Both
      fluorescein and indocyanine green angiography showed choriocapillaris atrophy in
      the posterior pole area and midperiphery. Macular optical coherence tomography
      showed thinning of the neurosensory retina. An electroretinographic examination
      showed no photopic or scotopic responses. The Boucher-Neuhauser syndrome should
      be included in the differential diagnosis of patients with retinitis pigment
      epithelium atrophy and degeneration.

PMID- 19096247
TI  - Pericardium plug in the repair of the corneoscleral fistula after Ahmed Glaucoma
      Valve explantation.
AB  - We report four cases in which a pericardium (Tutoplast) plug was used to repair a
      corneoscleral fistula after Ahmed Glaucoma Valve (AGV) explantation. In four
      cases in which the AGV tube had been exposed, AGV explantation was performed
      using a pericardium (Tutoplast) plug to seal the defect previously occupied by
      the tube. After debridement of the fistula, a piece of processed pericardium
      (Tutoplast), measured 1 mm in width, was plugged into the fistula and secured
      with two interrupted 10-0 nylon sutures. To control intraocular pressure, a new
      AGV was implanted elsewhere in case 1, phaco-trabeculectomy was performed
      concurrently in case 2, cyclophotocoagulation was performed postoperatively in
      case 3 and anti-glaucomatous medication was added in case 4. No complication
      related to the fistula developed at the latest follow-up (range: 12-26 months).
      The pericardium (Tutoplast) plug seems to be an effective method in the repair of
      corneoscleral fistulas resulting from explantation of glaucoma drainage implants.

PMID- 19096249
TI  - Transforming growth factor-beta does not induce endothelin-1 secretion in primary
      cultured human tenon's fibroblasts.

PMID- 19096248
TI  - A case of an asymptomatic intralenticular foreign body.
AB  - The purpose of this article is to report a case of an asymptomatic
      intralenticular metallic foreign body that was retained for 6 months. A 66-year
      old male visited our ophthalmology department because of decreased visual acuity
      in his left eye 6 months after he suffered ocular trauma while mowing. He had not
      been treated because he did not experience any discomfort. His corrected visual
      acuity was 0.4. Central corneal opacity, an intralenticular metallic foreign
      body, and an intact posterior capsule were observed on slit lamp examination.
      Phacoemulsification with posterior chamber lens implantation and simultaneous
      removal of the intralenticular foreign body was performed. Seventeen days after
      the operation, his corrected visual acuity was 1.0, the intraocular lens was well
      seated, and there was no intraocular inflammation. In this case report, a patient
      was found to have an intralenticular metallic foreign body retained for 6 months.
      During this time he did not experience any ocular dysfunction due to the foreign
      body. Mowing accidents are common in Korea. Despite the absence of symptoms,
      patients reporting a history of lawn mowing should be thoroughly examined.

PMID- 19096250
TI  - [Neuroendocrine carcinoma of the sigmoid colon].

PMID- 19096251
TI  - [Treatment of esophageal cancer].
AB  - Esophageal cancer is usually detected in the advanced stage due to its anatomical
      characteristics. Recently, early esophageal cancers are detected more frequently
      with the nationwide screening of digestive tract cancer and development of new
      endoscopic technology in Korea. From the treatment view point, esophageal cancer
      can be categorized into early, locally advanced resectable, locally advanced
      unresectable, and metastatic esophageal cancer. Traditionally, surgery has been
      the mainstay of treatment for resectable esophageal cancer. However, endoscopic
      resection can be another therapeutic option in selected early esophageal cancer
      cases. Although most studies with preoperative chemoradiotherapy and subsequent
      surgery in locally advanced resectable cancer could not demonstrate definite
      survival benefit, many authorities prefer this multimodality approach to surgery
      alone. Best supportive care is always necessary for those with unresectable
      esophageal cancer, and palliation for dysphagia can be considered according to
      the patients' status. For the best management of esophageal cancer, the
      development of diagnostic method for more accurate staging should be followed.

PMID- 19096252
TI  - [The changes in incidence of Crohn's disease and intestinal tuberculosis in
      Korea].
AB  - BACKGROUND/AIMS: The incidence of Crohn's disease (CD) has been steadily
      increasing in Korea due to westernized life style and widely used imaging studies
      such as colonoscopy. There were few studies about the status of longterm trend of
      CD and intestinal tuberculosis (IT). Therefore, we aimed to evaluate the trend of
      CD and IT in Korea. METHODS: We retrospectively reviewed the medical records of
      newly diagnosed 65 patients with CD and 54 patients with IT at Chonnam National
      University Hospital between January 1998 and August 2007. RESULTS: Between 1998
      and 2002, 16 and 40 patients were newly diagnosed as having CD and IT
      respectively, but between 2003 and 2007, 39 and 14 patients were newly diagnosed
      as having CD and IT respectively. CD patients (28.2+/-15.2 years) were younger
      than IT (46.2+/-18.5 years) (p=0.001). The male to female ratio of CD and IT were
      2:1 and 1.1:1, respectively. The most common symptom of CD and IT was abdominal
      pain. Longitudinal ulceration, hyperemia, luminal narrowing, pseudopolyp, and
      cobble stone appearance were more common in CD than in IT (p<0.05). CONCLUSIONS:
      While the incidence of CD has increased, the incidence of IT has fallen over the
      last decade.

PMID- 19096253
TI  - [Immunohistochemical analysis of nuclear factor, p38, and cyclin D1 proteins in
      premalignant lesions and carcinomas of the colorectal mucosa].
AB  - BACKGROUND/AIMS: Nuclear factor-kappaB p65 (NF-kappaB p65), nuclear factor
      kappaB1 p50 (NF-kappaB p50) have been shown to play a role in cell proliferation,
      apoptosis, cytokine production, and oncogenesis. Recently, p38 mitogen-activated
      protein kinase (MAPK)/ NF-kappaB/ cyclin D1 signaling pathway has been shown to
      play an important part in the pathogenesis of human cancers. This study was
      designed to investigate the expression of NF-kappaB p65, NF-kappaB p50, p38
      MAPKalpha, and cyclin D1 proteins in premalignant lesions of colon and colorectal
      adenocarcinoma. METHODS: Paraffin sections of 20 normal mucosa, 20 low-grade
      tubular adenoma, 20 high-grade tubular adenoma and 64 adenocarcinoma tissues were
      analysed immunohistochemically for the expression of NF-kappaB p65, NF-kappaB
      p50, p38 MAPKalpha, and cyclin D1 proteins. RESULTS: The expression of NF-kappaB
      p65, NF-kappaB p50, and p38 MAPKalpha proteins were significantly higher in
      adenocarcinoma tissue in comparison with that in normal mucosa, low-grade tubular
      adenoma, and high-grade tubular adenoma tissues. Expression of NF-kappaB p50 was
      more frequent in poorly differentiated histologic grade, presence of nodal
      metastasis, and advanced stage. Expression of p38 MAPKalpha protein was higher in
      advanced tumor stage, presence of nodal metastasis and advanced stage.
      Synchronous expression of NF-kappaB p65, NF-kappaB p50, p38 MAPKalpha, and cyclin
      D1 proteins were significantly higher in adenocarcinoma tissue. CONCLUSIONS: With
      the increased expression of NF-kappaB p65, NF-kappaB p50, and p38 MAPKalpha
      proteins, p38 MAPK/ NF-kappaB/ cyclin D1 signaling pathway may play a role in the
      pathogenesis of colorectal carcinoma.

PMID- 19096254
TI  - [Clinical outcomes of lamivudine therapy and HLA alleles in chronic hepatitis B
      patients].
AB  - BACKGROUND/AIMS: The human leukocyte antigen (HLA) system is an integral
      component of immune response. Highly polymorphic HLA genes may play a pivotal
      role in the response of antiviral therapy. We investigated the effects of HLA
      gene polymorphism on the clinical outcome of chronic hepatitis B patients who
      received lamivudine treatment. METHODS: Depending on their clinical response to
      lamivudine therapy, a total of sixty one patients were divided into following
      groups; non-responders, viral breakthroughers, relapsers, and seroconverters. HLA
      A, -B, -Cw, -DRB and HLA-DRB1 alleles typing was performed on each group through
      the polymerase chain reaction and the sequence-specific oligonucleotide
      hybridization method. The distribution patterns of HLA-A, HLA-B, HLA-Cw, HLA-DRB,
      and HLA-DRB1 were then analysed. RESULTS: When non-responders were compared to
      the other groups, high frequencies in HLA-Cw1, HLA-DRB14 and HLA-DRB4 (p=0.015,
      0.033 and 0.004 respectively) were evident. When seroconverters were compared to
      viral breakthroughers, high frequencies in HLA-A2 and HLA-DRB4 (p=0.048, 0.025
      respectively) were evident. CONCLUSIONS: Our data suggests that HLA-A2, HLA-Cw1,
      HLA-DRB14 genes are related to the clinical outcomes of lamivudine treatment in
      chronic hepatitis B patients. These genes may be used in the prediction of the
      clinical outcome of lamivudine therapy in chronic hepatitis B patients.

PMID- 19096255
TI  - [Clinical, radiological and pathological exploration of focal nodular hyperplasia
      of liver reported in Korea].
AB  - BACKGROUND/AIMS: Focal nodular hyperplasia (FNH) is mandatory to be
      differentiated from other hepatic tumorous conditions such as hepatocellular
      carcinoma and adenoma. The purpose of this study was to explore the clinical,
      radiological and pathological features of FNH cases reported in Korea. METHODS:
      We have searched the journals from the web site "http://koreamed.org" using
      keywords "focal nodular hyperplasia" and "liver" - total of 38 cases of FNH, 37
      cases from 17 published articles and one case from our experience confirmed
      histologically, were reviewed and analyzed. RESULTS: Thirty eight cases were
      diagnosed between gestational age of 36 weeks and 67 years. Seventeen female
      patients (45%) had no history of taking oral contraceptives. Twenty cases (52.6%)
      experienced clinical symptoms such as abdominal pain and palpable mass. Computed
      tomography revealed contrast-enhancement in 34 nodules (85%) and typical central
      stellate scar in 9 (22.5%) of 40 nodules. Magnetic resonance imaging showed T1
      weighted low signal in 18 (60%) and T2 weighted high signal in 22 (73.3%) of 30
      nodules. Six (60%) of 10 cases showed hypervascular staining on hepatic
      angiography. Among 38 cases, 32 (84.2%) cases had single nodule and their mean
      size was 3.9 cm (0.5-16 cm). Pathologically, fibrous septa, proliferation of bile
      ductules and arterial wall thickening were seen in most cases. CONCLUSIONS: Of
      all the FNH cases reported in Korea, there were some differences in clinical
      aspects of sex ratio, accompanying clinical symptoms, and relationship with oral
      contraceptives, compared with previous reports. Further prospective studies are
      needed by means of nation-wide clinical survey and analysis.

PMID- 19096256
TI  - [A case of giant Brunner's gland hyperplasia combined with adenomyomatous
      hyperplasia].
AB  - Brunner's gland hyperplasia is a rare tumor of the duodenum and might also be an
      unusual cause of gastrointestinal bleeding. In symptomatic patients, treatment
      requires either surgical resection or endoscopic polypectomy. We report a case of
      upper gastrointestinal bleeding from a pedunculated Brunner's gland hyperplasia
      in the duodenal bulb. Endoscopic resection using the detachable snare and
      hemoclipping was instituted to remove a large pedunculated polyp. The pathologic
      diagnosis was Brunner's gland hyperplasia with adenomyomatous hyperplasia.

PMID- 19096257
TI  - [Hepatocellular carcinoma with metastasis to the cavernous sinus of skull base
      causing ptosis].
AB  - The cavernous sinus of skull base is a extremely rare metastastatic site for
      hepatocellular carcinoma (HCC). A 51-year-old man was diagnosed with HCC by liver
      biopsy and palliative radiotherapy on HCC including main portal vein was
      performed. One month later, he was admitted due to sudden onset ptosis.
      Neurologic findings were normal except for abnormal movement of right eye, and it
      raised the possibility of abnormality in the right occulomotor, trochlear and the
      abducens nerves. Contrast-enhanced CT scan of brain showed a mass with
      homogeneous enhancement involving the right cavernous sinus. T2-weighted axial MR
      images demonstrated a homogeneous mass with intermediate signal intensity, and
      contrast-enhanced axial T1-weighted MR images demonstrated a mass with
      homogeneous enhancement in the right cavernous sinus. We describe a case of HCC
      metastasis to the cavernous sinus with symptoms of ptosis and disturbance of
      right eyeball movement.

PMID- 19096258
TI  - [Obstructive jaundice due to compression of the common bile duct by right hepatic
      artery originated from gastroduodenal artery].
AB  - Obstructive jaundice by vascular compression is rare. The causative arteries were
      identified as the right hepatic artery, gastroduodenal artery, cystic artery,
      proper hepatic artery, and an unspecified branch of the common hepatic artery.
      Also the venous system, such as enlarging collateral veins in cases of portal
      hypertension was a causative vessel. Herein, we describe a case of a proximal
      choledocholithiasis due to compression of the common bile duct by right hepatic
      artery originated from gastroduodenal artery. Final diagnosis and treatment were
      achieved through an operation.

PMID- 19096259
TI  - [A case of systemic amyloidosis with pancreatic involvement mimicking autoimmune
      pancreatitis].
AB  - Systemic amyloidosis is a disorder characterized by extracellular deposition of
      amyloid in various organs and tissues including the kidney, heart, and liver.
      However, pancreatic involvement is rare, and has not been reported in Korea.
      Systemic amyloisosis involving pancreas needs to be differentiated from several
      pancreatic diseases because of diffuse pancreatic enlargement and partial
      stricture or obstruction of main pancreatic duct. Recently, we experienced a 60
      year old man who was suspected as autoimmune pancreatitis or infiltrative
      disorders on imaging studies, and finally diagnosed as systemic amyloidosis
      involving pancreas and liver on biopsy examination. We report the case with
      review of the relevant literatures.

PMID- 19096261
TI  - Strategic levers for a high-performing health system.

PMID- 19096262
TI  - Equity of what in healthcare? Why the traditional answers don't help policy--and
      what to do in the future.

PMID- 19096263
TI  - Cost control, equity and efficiency: can we have it all?

PMID- 19096264
TI  - Balancing equity issues in health systems: perspectives of primary healthcare.

PMID- 19096265
TI  - The reform of health and social services in Quebec.

PMID- 19096266
TI  - Balancing equity issues in health systems: the example of Vancouver Coastal
      Health.

PMID- 19096267
TI  - Strategic purchasing to improve health system performance: key issues and
      international trends.

PMID- 19096268
TI  - Strategic purchasing: the experience in England.

PMID- 19096269
TI  - Strategic purchasing in home and community care across Canada: coming to grips
      with "what" to purchase.

PMID- 19096270
TI  - Strategic outsourcing by a regional health authority: the experience of the
      Vancouver Island Health Authority.

PMID- 19096271
TI  - Thoughts on the day: strategic purchasing and equity.

PMID- 19096272
TI  - The next step on the road to high efficiency: finding common ground between
      equity and performance.

PMID- 19096273
TI  - Finding a window into the skin: it depends on the color of your skin. 2002.

PMID- 19096277
TI  - Needs assessment for continuing education activity.

PMID- 19096278
TI  - Evidence-based medicine in wound care: time for a new paradigm.

PMID- 19096279
TI  - CMS announced new 2009 HCPCS codes for skin substitutes.

PMID- 19096280
TI  - Transdermal oxygen delivery to diabetic wounds: a report of 6 cases.
AB  - OBJECTIVE: To evaluate the use of a transdermal sustained oxygen delivery system
      to promote the healing of chronic lower extremity wounds in patients with
      diabetes. METHODS: Six patients (5 men, 1 woman; age range, 32-77 years) with
      diabetes and chronic lower extremity wounds unresponsive to previous multimodal
      therapy were treated with transdermal sustained oxygen. The transdermal sustained
      oxygen delivery device (EpiFLO; Ogenix Corp, Cleveland, Ohio) delivered 100%
      oxygen at 3 mL/h with ambient humidity, 24 h/day, directly to the wound site,
      which was covered by an occlusive dressing. RESULTS: Despite chronicity of wounds
      (aged 4 months to >15 years) and nonresponsiveness to previous treatments, all
      wounds in this case series treated with transdermal sustained oxygen therapy
      improved within 2 to 20 weeks, within which time 5 of the 6 wounds had healed
      completely. In 2 cases, scheduled amputations were prevented. CONCLUSION: The
      results of the 6 cases reported here strongly support the use of transdermal
      sustained oxygen therapy in promoting the healing of diabetic foot and leg ulcers
      refractory to previous treatments. In addition, amputation was prevented in 2
      cases, thus reducing prolonged costly patient care.

PMID- 19096281
TI  - Maggot therapy for wound management.

PMID- 19096283
TI  - Standardization of wound photography using the Wound Electronic Medical Record.

PMID- 19096284
TI  - Body image and facial burns.
AB  - PURPOSE: To provide the wound care practitioner with a framework for managing
      altered body image. TARGET AUDIENCE: This continuing education activity is
      intended for physicians and nurses with an interest in skin and wound care.
      OBJECTIVES: After reading this article and taking this test, the reader should be
      able to: 1. Describe theories and research relating to normal and altered body
      image. 2. Discuss the effect of facial burns on body image.

PMID- 19096286
TI  - Monitoring laboratory values: protein and albumin.

PMID- 19096287
TI  - Simultaneous measurement of perceptual and motor cortical potentials:
      implications for assessing information processing in traumatic brain injury.
AB  - OBJECTIVE: Psychomotor slowing is a common manifestation of traumatic brain
      injury. Previous electrophysiological studies of traumatic brain injury have
      focused on abnormal attentional and perceptual responses to incoming stimuli. We
      hypothesize that traumatic brain injury is also associated with abnormal cortical
      components of motor execution. DESIGN: To test this hypothesis, we analyzed event
      related potentials of 22 subjects (11 with a history of severe traumatic brain
      injury and 11 age-matched healthy subjects) during oddball discrimination tasks.
      In addition to the usual stimulus-locked averaging of electrophysiological data
      to reveal cognitive components, such as the P300, we also analyzed subjects'
      response-locked data to reveal motor potential waveforms. To focus on generalized
      effects across modality, analyses were performed on composite measures from both
      auditory and visual event-related potentials. RESULTS: (1) Traumatic brain injury
      subjects had abnormal P300 responses (with reduced amplitude and prolonged
      latency) in both sensory modalities. (2) Traumatic brain injury subjects' motor
      potential waveforms showed significantly reduced amplitude in both sensory
      modalities. (3) Abnormalities in P300 latency, amplitude, and motor potential
      amplitude (effect sizes = 1.2-1.5 SD) were greater than behavioral slowing, as
      measured by reaction times (0.7 SD). (4) P300 latency and motor potential
      amplitude together accounted for much of the reaction time prolongation (r =
      0.73). CONCLUSIONS: This study demonstrates the value of concurrently analyzing
      stimulus-locked and response-locked event-related potential data to evaluate
      cortical components of perceptual and motor processing. The present findings
      indicate that patients with traumatic brain injury have impairments in both the
      perceptual interpretation of incoming stimuli and the execution of motor
      responses and that both abnormalities contribute to psychomotor slowing in
      patients with traumatic brain injury.

PMID- 19096288
TI  - Effects of a foot drop neuroprosthesis on functional abilities, social
      participation, and gait velocity.
AB  - DESIGN: Prospective, single group, repeated measures 1-yr follow-up of 16
      patients (aged 55 +/- 14.6 yrs) with chronic hemiparesis who used a
      neuroprosthesis for 1 yr and were available for follow-up. Outcome measures
      included the Short Version of the Stroke Impact Scale, the Participation domain
      of the Stroke Impact Scale, and the gait velocity. RESULTS: Significant increases
      of 18.0% in physical functioning and of 25.2% in participation in community life
      were attained 2 mos after the application of the neuroprosthesis. The gains were
      maintained at the 1-yr follow-up. Gait velocity increased significantly by 29.2%
      by 2 mos, with significant further increases of 22.6% observed at the 1-yr follow
      up. CONCLUSIONS: Use of the studied neuroprosthesis to correct foot drop
      significantly enhanced functional abilities, social reintegration, and gait
      velocity. These results support the prolonged use of the neuroprosthesis in
      patients with chronic hemiparesis.

PMID- 19096290
TI  - Self-delivered home-based mirror therapy for lower limb phantom pain.
AB  - Home-based patient-delivered mirror therapy is a promising approach in the
      treatment of phantom limb pain. Previous studies and case reports of mirror
      therapy have used a therapist-guided, structured protocol of exercises. No case
      report has described treatment for either upper or lower limb phantom pain by
      using home-based patient-delivered mirror therapy. The success of this case
      demonstrates that home-based patient-delivered mirror therapy may be an
      efficacious, low-cost treatment option that would eliminate many traditional
      barriers to care.

PMID- 19096289
TI  - Examination of selected clinical factors and medication use as risk factors for
      pneumonia during stroke rehabilitation: a case-control study.
AB  - OBJECTIVE: To assess the association of selected clinical factors and specific
      medication use (proton pump inhibitors, H2 receptor antagonists [H2 blockers],
      and angiotensin-converting enzyme inhibitors) with presence of pneumonia in
      patients with stroke undergoing acute inpatient rehabilitation. DESIGN: Matched
      case-control study in a freestanding urban academic inpatient acute
      rehabilitation hospital. Participants were 72 stroke survivors, consisting of 36
      patients who developed pneumonia during rehabilitation hospitalization
      individually matched in order of decreasing priority on age, sex, stroke side,
      depth, and severity with 36 patients with stroke not developing pneumonia.
      Potential risk factors, including severe dysphagia, dietary interventions,
      presence of tracheostomy or feeding tube, and specific medications, were assessed
      for association with pneumonia during rehabilitation using separate univariate
      and multivariate analyses. Functional change was assessed using the functional
      independence measure. RESULTS: Although pneumonia was associated with proton pump
      inhibitors or H2 blockers (odds ratio, 3.3; 95% confidence interval, 1.0-13.7),
      any feeding tube (odds ratio: 5.0; 95% confidence interval, 1.4-27.0), severe
      dysphagia (odds ratio: 15.0; 95% confidence interval, 2.3-631), and tracheostomy
      (odds ratio: 10; 95% confidence interval, 1.4-434.0) on univariate evaluation,
      none of these individual factors was significantly associated with pneumonia in a
      multivariate model. Risk factors were found to be highly related to each other.
      Odds of pneumonia did not significantly decrease with angiotensin-converting
      enzyme inhibitors (odds ratio: 0.9; 95% confidence interval, 0.2-3.0). Patients
      with pneumonia had a significantly lower functional independence measure score at
      discharge. CONCLUSIONS: A reduction in pneumonia was not found with the use of
      angiotensin-converting enzyme inhibitors. Although tracheostomies, feeding tubes,
      proton pump inhibitor or H2 blocker use, and the presence of dysphagia were
      identified as risk factors for pneumonia on univariate analyses, none of these
      factors demonstrated an independent association with pneumonia on multivariate
      analyses. It may be more that the underlying impairment, rather than the assessed
      interventions, may confer greater risk of pneumonia in the poststroke patient.

PMID- 19096291
TI  - Sciatic nerve paralysis following arteriovenous malformation embolization.

PMID- 19096293
TI  - In this issue/abstract thinking: thinking inside the box.

PMID- 19096292
TI  - Practical solutions to the challenges of uncontrolled hypertension: a white
      paper.
AB  - This white paper is an urgent call to action from an international group of
      physicians. The continued failure to control hypertension takes an unacceptable
      toll on patients, families and society and it must be addressed. Any patient with
      blood pressure of 140/90 mmHg or greater can be characterized as a 'challenging
      patient', is at significant risk, and requires persistent optimization of therapy
      until target blood pressure is achieved. Six key challenges in reaching this goal
      blood pressure are described: (1) inadequate primary prevention; (2) faulty
      awareness of risk; (3) lack of simplicity; (4) therapeutic inertia; (5)
      insufficient patient empowerment; and (6) unsupportive healthcare systems. This
      white paper identifies straightforward actions that will produce rapid
      improvements in the management of hypertension, with a simple aim: to treat all
      challenging patients effectively to goal blood pressure, preventing disability
      and saving lives.

PMID- 19096294
TI  - Childhood psychopathology can be really bad for your health.

PMID- 19096295
TI  - Learning and memory, part II: molecular mechanisms of synaptic plasticity.

PMID- 19096296
TI  - Prevalence of enuresis and its association with attention-deficit/hyperactivity
      disorder among U.S. children: results from a nationally representative study.
AB  - OBJECTIVE: There are no published nationally representative prevalence estimates
      of enuresis among children in the United States using standardized diagnostic
      criteria. This study sets out to describe the prevalence, demographic correlates,
      comorbidities, and service patterns for enuresis in a representative sample of
      U.S. children. METHOD: The diagnosis of enuresis was derived from parent-reported
      data for "enuresis, nocturnal" collected using the computerized version of the
      Diagnostic Interview Schedule for Children (C-DISC 4.0) from a nationally
      representative sample of 8- to 11-year-old children (n = 1,136) who participated
      in the 2001-2004 National Health and Nutrition Examination Surveys. RESULTS: The
      overall 12-month prevalence of enuresis was 4.45%. The prevalence in boys (6.21%)
      was significantly greater than that in girls (2.51%). Enuresis was more common at
      younger ages and among black youth. Attention-deficit/hyperactivity disorder
      (ADHD) was strongly associated with enuresis (odds ratio 2.88; 95% confidence
      interval 1.26-6.57). Only 36% of the enuretic children had received health
      services for enuresis. CONCLUSIONS: Enuresis is a common condition among children
      in the United States. Few families seek treatment for enuresis despite the
      potential for adverse effects on emotional health. Child health care
      professionals should routinely screen for enuresis and its effects on the
      emotional health of the child and the family. Assessment of ADHD should routinely
      include evaluation for enuresis and vice versa. Research on the explanations for
      the association between enuresis and ADHD is indicated.

PMID- 19096298
TI  - First Americans: psychopathology and a shortage of professionals.

PMID- 19096299
TI  - EGFR T790M mutation: a double role in lung cancer cell survival?
AB  - Even though lung cancer patients harboring a mutation in the epidermal growth
      factor receptor (EGFR) gene exhibit an initial dramatic response to EGFR tyrosine
      kinase inhibitors (EGFR-TKIs), acquired resistance is almost inevitable after a
      progression-free period of approximately 10 months. A secondary point mutation
      that substitutes methionine for threonine at amino acid position 790 (T790M) is a
      molecular mechanism that produces a drug-resistant variant of the targeted
      kinase. The T790M mutation is present in about half of the lung cancer patients
      with acquired resistance, and reported to act by increasing the affinity of the
      receptor to adenosine triphosphate, relative to its affinity to TKIs.
      Nevertheless, several lines of evidence indicate that the T790M mutation confers
      growth advantage to cancer cells, and it was shown that mice expressing
      tetracycline-inducible EGFR transgenes harboring the T790M mutation develop lung
      tumors. Thus, T790M mutation seems to play a double role in the survival of lung
      cancer cells. Several second-generation EGFR-TKIs are currently being developed
      to overcome the acquired resistance caused by the T790M mutation. MET (met proto
      oncogene) amplification or activation of IGF1R are reported as alternative
      mechanisms for acquired resistance to EGFR-TKIs. Clarification of the pathways
      leading to acquired resistance is essential to maximize the efficacy of EGFR-TKI
      therapy for patients with lung cancer.

PMID- 19096300
TI  - Activation of MET by gene amplification or by splice mutations deleting the
      juxtamembrane domain in primary resected lung cancers.
AB  - INTRODUCTION: MET (Met proto-oncogene) activation either by gene amplification or
      mutation is implicated in various types of human cancers. For lung cancer, MET
      gene amplification is reported to occur in a subset of adenocarcinomas. Although
      somatic mutations of MET in lung adenocarcinomas are rare, all but one of those
      reported so far entail a splice mutation deleting the juxtamembrane domain for
      binding the c-Cbl E3-ligase; normally such binding leads to ubiquitination and
      receptor degradation, and loss of this domain leads to MET activation. The
      purpose of this study was to clarify in the role of MET activation in lung
      carcinogenesis. MATERIALS AND METHODS: MET gene copy number was determined by
      real-time quantitative polymerase chain reaction in 187 of the patients with lung
      cancer and the MET gene splice mutation deleting the juxtamembrane domain was
      examined by direct sequencing in 262. The results were correlated with various
      clinical and pathologic features including mutations of the epidermal growth
      factor receptor, KRAS, and HER2 genes. RESULTS: All the instances of MET
      activation occurred in patients with adenocarcinomas. The prevalences of MET gene
      amplification and splice mutations were 1.4% (2 of 148) and 3.3% (7 of 211),
      respectively. We identified four different intronic mutations that disrupted a
      splice consensus sequence in genomic DNA. Activation of MET and mutations of the
      epidermal growth factor receptor, KRAS, and HER2 genes had strict mutual
      exclusionary relationships. CONCLUSIONS: About 5% of pulmonary adenocarcinomas in
      this cohort of Japanese patients were driven by activated MET by gene
      amplification or splice mutations. Such patients would be candidates for targeted
      therapy against MET.

PMID- 19096301
TI  - Using whole genome amplification (WGA) of low-volume biopsies to assess the
      prognostic role of EGFR, KRAS, p53, and CMET mutations in advanced-stage non
      small cell lung cancer (NSCLC).
AB  - BACKGROUND: Progression of non-small cell lung cancer (NSCLC) from early- to late
      stage may signify the accumulation of gene mutations. An advanced-stage tumor's
      mutation profile may also have prognostic value, guiding treatment decisions.
      Mutation detection of multiple genes is limited by the low amount of
      deoxyribonucleic acid extracted from low-volume diagnostic lung biopsies. We
      explored whole genome amplification (WGA) to enable multiple molecular analyses.
      METHODS: Eighty-eight advanced-stage NSCLC patients were enrolled. Their low
      volume lung biopsies underwent WGA before direct sequencing for epidermal growth
      factor receptor (EGFR), KRAS (rat sarcoma virus), p53, and CMET (mesenchymal
      epithelial transition factor) mutations. Overall survival impact was examined.
      Surgically-resected tumors from 133 early-stage NSCLC patients were sequenced for
      EGFR, KRAS and p53 mutations. We compared the mutation frequencies of both
      groups. RESULTS: It is feasible for low-volume lung biopsies to undergo WGA for
      mutational analysis. KRAS and CMET mutations have a deleterious effect on overall
      survival, hazard ratios 5.05 (p = 0.009) and 23.65 (p = 0.005), respectively.
      EGFR and p53 mutations, however, do not have a survival impact. There also does
      not seem to be significant differences in the frequency of mutations in EGFR,
      KRAS, and p53 between early- and advanced-stage disease: 20% versus 24% (p =
      0.48), 29% versus 27% (p = 0.75), 10% versus 6% (p = 0.27), respectively.
      CONCLUSIONS: In advanced-stage NSCLC, KRAS, and CMET mutations suggest poor
      prognosis, whereas EGFR and p53 mutations do not seem to have survival impact.
      Mutations in EGFR, KRAS and p53 are unlikely to be responsible for the
      progression of NSCLC from early- to late-stage disease. WGA may be used to expand
      starting deoxyribonucleic acid from low-volume lung biopsies for further analysis
      of advanced-stage NSCLC.

PMID- 19096302
TI  - Prognostic implication of EGFR, KRAS, and TP53 gene mutations in a large cohort
      of Japanese patients with surgically treated lung adenocarcinoma.
AB  - INTRODUCTION: Although mutation of the epidermal growth factor receptor (EGFR)
      gene is predictive for the response to EGFR-tyrosine kinase inhibitor, its
      prognostic impact for patients without EGFR-tyrosine kinase inhibitor treatment
      remains controversial. We examined for EGFR, KRAS or TP53 mutations in a
      consecutive large cohort of patients with lung adenocarcinoma, and evaluated
      their prognostic impact. METHODS: We analyzed 397 patients with lung
      adenocarcinoma who underwent potentially curative pulmonary resection. Total
      ribonucleic acid was extracted and direct sequencing of each gene was performed
      after reverse transcription-polymerase chain reaction. RESULTS: We found that 196
      patients (49%) had EGFR mutations. Of these, 83 were exon 19 deletions (42%) and
      92 were L858R (47%). Univariate analysis showed that patients with EGFR mutations
      survived for a longer period than those without mutations (p = 0.0046). However,
      there was no difference in overall survival between the patients with exon 19
      deletion and those with L858R (p = 0.4144). Patients with KRAS mutations or TP53
      mutations tended to survive for a shorter period (p = 0.2183 and 0.0230,
      respectively). Multivariate analysis using the Cox proportional hazards model
      revealed that smoking status (p = 0.0310) and disease stage (p < 0.0001) were
      independent prognostic factors. However, none of the gene mutations was
      independent prognostic factors (EGFR, p = 0.3225; KRAS, p = 0.8500; TP53, p =
      0.3191). CONCLUSIONS: EGFR, KRAS, and TP53 gene mutations were not independently
      associated with the prognosis for Japanese patients with surgically treated lung
      adenocarcinoma.

PMID- 19096303
TI  - Preliminary investigation of the clinical significance of detecting circulating
      tumor cells enriched from lung cancer patients.
AB  - BACKGROUND: Enumeration of circulating tumor cells (CTCs) may be valuable for
      lung cancer treatment and monitoring cancer patient relapse. In the present study
      we report clinical significance of lung cancer CTC. METHODS: CTCs were enriched
      from peripheral blood of 47 lung cancer patients by means of a modified
      enrichment strategy, followed by identification with immunofluorescence staining
      using anticytokeratins 18 and 19 monoclonal antibodies. RESULTS: A control group
      consisted of 18 healthy donors and 13 nonmalignant pulmonary tuberculosis
      patients had no positive subject detected. Among 41 newly diagnosed and 6
      recurrent lung cancer patients (3 stage I-II, 22 stage III and 22 stage IV)
      including 27 adenocarcinoma (ADC), 7 squamous cell carcinoma and 13 small cell
      lung cancer (SCLC), positive detection rate of newly diagnosed patients with CTC
      >/=2/7.5 ml blood was 78% (ADC stage III), 75% (squamous cell carcinoma stage
      III) and 60% (SCLC stage III), respectively. Whereas 46% (ADC IV) and 71% (SCLC
      IV) were observed for stage IV patients. Recurrent patients showed highest
      detection sensitivity of 83%. A small scale follow-up study was performed on 12
      patients following 2 courses of first line chemotherapy. This demonstrated a good
      correlation of CTC enumeration with radiographic response. CONCLUSIONS: Results
      of the present study suggest potential clinical utilities of CTC enumeration on
      lung cancer patients in terms of rapid evaluation of chemotherapy effect in real
      time and monitoring lung cancer recurrence. A large scale of study which is
      necessary for further validation of the significance of lung cancer CTC is being
      performed.

PMID- 19096304
TI  - Prognostic factors for survival in extensive stage small cell lung cancer (ED
      SCLC): the importance of smoking history, socioeconomic and marital statuses, and
      ethnicity.
AB  - BACKGROUND: : We investigated whether independent prognostic factors for overall
      survival (OS) in non-small cell lung cancer such as ethnicity, smoking history,
      socioeconomic, and marital statuses are also applicable to extensive stage small
      cell lung cancer (ED-SCLC). METHODS: : SCLC patients diagnosed from 1991 to 2005
      from 3 Southern California counties were identified. Prognostic factors for ED
      SCLC patients were evaluated by univariate and multivariate analysis. RESULTS: :
      Of the 4782 SCLC patients analyzed, only 2.5% of the patients were never-smokers
      and 71.7% of patients presented with ED-SCLC. By multivariate analysis, a
      positive smoking status was a statistically significant poor prognostic factor
      for OS in ED-SCLC patients (versus never-smoker; hazard ratio [HR] = 1.310; p =
      0.0125), in addition low socioeconomic status (SES) (from the lowest to the
      highest SES score; ptrend = 0.0128) and being unmarried (versus married; HR =
      1.179; p < 0.0001). Asian ethnicity was a favorable prognostic factor in ED-SCLC
      (versus Caucasian; HR = 0.785; p = 0.0076). Female gender was another independent
      favorable prognostic factor (versus male; HR = 0.823; p < 0.0001). CONCLUSIONS: :
      A positive history of smoking, low SES, and being unmarried are independent
      unfavorable prognostic factors for OS in ED-SCLC while Asian ethnicity and female
      gender are independent favorable prognostic factors for OS in ED-SCLC by
      multivariate analysis.

PMID- 19096305
TI  - EBUS-TBNA for the clarification of PET positive intra-thoracic lymph nodes-an
      international multi-centre experience.
AB  - INTRODUCTION: To determine the sensitivity and accuracy of endobronchial
      ultrasound guided transbronchial needle aspiration (EBUS-TBNA) for clarification
      of the nature of fluorodeoxyglucose-positron emission tomography (FDG) positive
      hilar and/or mediastinal lymph nodes in patients with (suspected) lung cancer.
      METHODS: All consecutive patients who had undergone EBUS-TBNA alone for
      assessment of abnormal FDG-uptake in hilar and/or mediastinal lymph nodes between
      January 2005 and August 2007 were reviewed. RESULTS: One-hundred-nine patients
      underwent EBUS-TBNA of 127 positron emission tomography positive lymph nodes.
      Hilar (station 10 or 11) nodes (N1 or N3) were aspirated in 26 patients and
      mediastinal (stations 2, 4, 7) nodes (N2 or N3) in 90 patients. In 7 patients
      both hilar and mediastinal nodes were sampled. There were no procedure-related
      complications. Malignancy was detected in 77 (71%) cases. Thirty-two patients
      were tumor negative by EBUS-TBNA; subsequent surgical biopsy in 19 showed
      malignancy in 7. In four cases the false negative result was due to sampling
      error and in three cases due to detection error. In 13 cases surgical staging was
      not performed although long term follow-up in 3 showed no evidence of malignancy.
      The sensitivity and accuracy of EBUS-TBNA for malignancy in patients with
      reference pathology was 91% and 92%, respectively. The negative predictive value
      was 60%. If the 10 cases for which confirmatory surgical staging was not
      performed are assumed to be false negative results, overall sensitivity and
      accuracy were 82% and 84%, respectively. CONCLUSIONS: EBUS-TBNA offers an
      effective accurate, minimally invasive strategy for evaluating FDG avid hilar and
      mediastinal lymph nodes. However, negative findings should be confirmed by
      surgical staging.

PMID- 19096306
TI  - Detection and localization of intraepithelial neoplasia and invasive carcinoma
      using fluorescence-reflectance bronchoscopy: an international, multicenter
      clinical trial.
AB  - OBJECTIVES: The primary objective of this study was to evaluate the benefit of
      using a new fluorescence-reflectance imaging system, Onco-LIFE, for the detection
      and localization of intraepitheal neoplasia and early invasive squamous cell
      carcinoma. A secondary objective was to evaluate the potential use of
      quantitative image analysis with this device for objective classification of
      abnormal sites. DESIGN: This study was a prospective, multicenter, comparative,
      single arm trial. Subjects for this study were aged 45 to 75 years and either
      current or past smokers of more than 20 pack-years with airflow obstruction,
      forced expiratory volume in 1 second/forced vital capacity less than 75%,
      suspected to have lung cancer based on either sputum atypia, abnormal chest
      roentgenogram/chest computed tomography, or patients with previous curatively
      treated lung or head and neck cancer within 2 years. MATERIALS AND METHODS: The
      primary endpoint of the study was to determine the relative sensitivity of white
      light bronchoscopy (WLB) plus autofluorescence-reflectance bronchoscopy compared
      with WLB alone. Bronchoscopy with Onco-LIFE was carried out in two stages. The
      first stage was performed under white light and mucosal lesions were visually
      classified. Mucosal lesions were classified using the same scheme in the second
      stage when viewed with Onco-LIFE in the fluorescence-reflectance mode. All
      regions classified as suspicious for moderate dysplasia or worse were biopsied,
      plus at least one nonsuspicious region for control. Specimens were evaluated by
      the site pathologist and then sent to a reference pathologist, each blinded to
      the endoscopic findings. Positive lesions were defined as those with
      moderate/severe dysplasia, carcinoma in situ (CIS), or invasive carcinoma. A
      positive patient was defined as having at least one lesion of moderate/severe
      dysplasia, CIS, or invasive carcinoma. Onco-LIFE was also used to quantify the
      fluorescence-reflectance response (based on the proportion of reflected red light
      to green fluorescence) for each suspected lesion before biopsy. RESULTS: There
      were 115 men and 55 women with median age of 62 years. Seven hundred seventy-six
      biopsy specimens were included. Seventy-six were classified as positive (moderate
      dysplasia or worse) by pathology. The relative sensitivity on a per-lesion basis
      of WLB + FLB versus WLB was 1.50 (95% confidence interval [CI], 1.26-1.89). The
      relative sensitivity on a per-patient basis was 1.33 (95% CI, 1.13-1.70). The
      relative sensitivity to detect intraepithelial neoplasia (moderate/severe
      dysplasia or CIS) was 4.29 (95% CI, 2.00-16.00) and 3.50 (95% CI, 1.63-12.00) on
      a per-lesion and per-patient basis, respectively. For a quantified fluorescence
      reflectance response value of more than or equal to 0.40, a sensitivity and
      specificity of 51% and 80%, respectively, could be achieved for detection of
      moderate/severe dsyplasia, CIS, and microinvasive cancer. CONCLUSIONS: Using
      autofluorescence-reflectance bronchoscopy as an adjunct to WLB with the Onco-LIFE
      system improves the detection and localization of intraepitheal neoplasia and
      invasive carcinoma compared with WLB alone. The use of quantitative image
      analysis to minimize interobserver variation in grading of abnormal sites should
      be explored further in future prospective clinical trial.

PMID- 19096307
TI  - Simple laboratory parameters which can determine the clinical state of patients
      after pneumonectomy for lung cancer.
AB  - INTRODUCTION: The clinical state of patients after pneumonectomy varies from
      normal to seriously impaired daily life. The objective of the study is to
      identify laboratory parameters which determine the clinical postpneumonectomy
      state. METHODS: Thirty-five patients who underwent pneumonectomy for lung
      carcinoma (mean age: 61.5 +/- 7.2 years, left sided: 23) were prospectively
      studied with preoperative and 6-month postoperative spirometry, Doppler
      echocardiography for calculation of right ventricular systolic pressure and
      arterial blood gas. The clinical postpneumonectomy state was defined as the class
      of dyspnea on exertion: I = on heavy exertion, II = on moderate exertion, III =
      on mild exertion, IV = on minimal exertion. RESULTS: Postoperative forced
      expiratory volume in 1 second (FEV1), forced vital capacity (FVC) and percent of
      the predicted FVC were significantly lower in patients with class III and IV than
      in patients with class I and II dyspnea, while right ventricular systolic
      pressure and percent reduction of FVC and FEV1 were significantly higher in
      patients with class IV dyspnea. On multiple regression analysis, postoperative
      FEV1 and percent reduction of FVC were found to strongly affect the
      postpneumonectomy state. Right pneumonectomy, obstructive pattern at preoperative
      spirometry, bronchial obstruction limited to up to three bronchopulmonary
      segments at preoperative bronchoscopy and predicted FEV1 less than 1.4 liter by
      the ventilation/perfusion lung scanning were connected with seriously impaired
      postpneumonectomy state. CONCLUSIONS: The postpneumonectomy state is affected by
      low actual postpneumonectomy FEV1 values and serious percent reduction of FVC
      from preoperative values. Right pneumonectomy together with obstructive
      ventilatory pattern and minimal bronchial obstruction are preoperative factors
      that result in serious reduction of FEV1 and percent reduction of FVC.

PMID- 19096308
TI  - Survival after trimodality treatment for superior sulcus and central T4 non-small
      cell lung cancer.
AB  - INTRODUCTION: For sulcus superior tumors and central cT4 tumors, low
      resectability and poor long-term survival rates are obtained with single-modality
      treatment. METHODS: Analysis of all consecutive patients in our prospective
      database, who had potentially resectable superior sulcus (cT3-T4) and central cT4
      tumors and were treated with induction chemoradiotherapy (two courses of
      cisplatin-etoposide) and concomitant radiotherapy (45 Gy/1.8 Gy) after
      multidisciplinary discussion. Surgery with attempted complete resection was
      performed in patients showing response or stable disease on computed tomography.
      RESULTS: Between April 2002 and February 2008, 32 consecutive patients were
      enrolled. Two patients did not complete the induction chemoradiotherapy. Thirty
      patients were reassessed after induction, 28 had response or stable disease by
      conventional imaging. Twenty-seven patients were surgically explored since one
      patient became medically inoperable during induction treatment. The overall
      complete resectability was 78% (25/32). Resection was microscopically incomplete
      (R1) in two patients. In 11 patients (41%), a pneumonectomy was performed, and in
      14 patients (52%), a chest wall resection was necessary. In 74% of the resected
      patients, there was a complete pathologic response or minimal residual
      microscopic disease. The mean postoperative hospital stay was 9.2 days with no
      hospital mortality and no bronchopleural fistula. With a median follow-up of 26.5
      months, 5-year survival rates are 74% in the intent-to-treat population (n = 32)
      and 77% in completely resected patients (n = 25), with no statistically
      significant difference between sulcus superior tumors and centrally located T4
      tumors. CONCLUSION: In patients with sulcus superior tumors and in selected
      patients with centrally located T4 tumors, trimodality treatment is feasible with
      acceptable morbidity and mortality. The complete resectability is high, and long
      term survival is promising.

PMID- 19096309
TI  - Definitive treatment of poor-risk patients with stage I lung cancer: a single
      institution experience.
AB  - PURPOSE: Lung cancer remains the leading cause of cancer death in both men and
      women. A substantial number of patients with early stage non-small cell lung
      cancer (NSCLC) are unfit for standard surgery due to cardiopulmonary dysfunction
      and/or other comorbidity. The appropriate management for this population has not
      been defined. METHODS: Retrospective analysis of patients with clinical stage I
      NSCLC judged to be unsuitable for lobectomy between 1996 and 2005. RESULTS:
      Ninety-six patients, representing 23% of all patients treated for clinical stage
      I NSCLC were included in this analysis. The median age was 73 years and most
      patients were female. Patients underwent limited resection (LR, n = 45), primary
      radiotherapy (RT, n = 39) or radiofrequency ablation (n = 12). With median follow
      up of 30 months, 61 patients remain alive. Actuarial 3-year survival is 65%
      following LR and 60% after primary RT. Local tumor relapse and distant metastases
      were observed with approximate equal probability following either LR or RT.
      CONCLUSION: Medical inoperability does not necessarily correspond to poor
      survival in patients with early stage NSCLC. A nihilistic approach is not
      warranted towards this population, and prospective trials are needed to better
      define optimal treatment strategies.

PMID- 19096310
TI  - Late complications of high-dose (>/=66 Gy) thoracic conformal radiation therapy
      in combined modality trials in unresectable stage III non-small cell lung cancer.
AB  - BACKGROUND: Combined modality treatment is the standard of care for patients
      (pts) with unresectable stage III non-small cell lung cancer. Dose escalation of
      radiotherapy is one strategy used to improve locoregional control and survival,
      but it increases the risk of both early and late treatment related toxicities.
      METHODS: From May 1996 to August 2004, a total of 112 stage III non-small cell
      lung cancer pts were treated on 4 phase I/II or phase II trials to assess the
      safety and feasibility of high-dose (60-90 Gy) thoracic conformal radiotherapy.
      Patients who received >/=66 Gy (n = 88) were included in an analysis of late
      complications. Late complications were defined as complications that developed or
      persisted >/=90 days postradiotherapy. The classic lung toxicities of radiation
      pneumonitis and fibrosis were not included in this analysis. RESULTS: Of the 88
      patients included in this analysis of late complications, 21 patients (24%)
      developed a late complication and a total of 28 late complications were observed.
      The late complications were: pulmonary (n = 5; bronchial stenosis [n = 3] and
      fatal pulmonary hemoptysis [n = 2]), esophageal (n = 6), cardiac (n = 9), osseous
      (n = 6), and second primary tumor (n = 2). The median survival for all patients
      enrolled on the 4 trials (with 95% confidence interval [CI]) was 24.7 months
      (18.1-30.4 months), and the 5-year overall survival (with 95% CI) was 24% (16
      32%). Data to assess for radiographic evidence of local progression were
      available for 99 patients, and the rate of local progression was 43% (95% CI 34
      53%). CONCLUSIONS: High-dose thoracic conformal radiotherapy is feasible and
      results in promising survival outcomes. Late complications occur in a minority of
      patients.

PMID- 19096311
TI  - RTOG 0017: a phase I trial of concurrent gemcitabine/carboplatin or
      gemcitabine/paclitaxel and radiation therapy ("ping-pong trial") followed by
      adjuvant chemotherapy for patients with favorable prognosis inoperable stage
      IIIA/B non-small cell lung cancer.
AB  - PURPOSE: The optimal dose of gemcitabine that can be used with concurrent
      radiation therapy for locally advanced non-small cell lung cancer has not been
      well defined. This trial addresses this question in an alternating sequence "ping
      pong" design trial to find the maximum tolerated dose (MTD) for
      gemcitabine/carboplatin (Sequence A) or gemcitabine/paclitaxel (Sequence B) and
      thoracic radiation therapy followed by adjuvant gemcitabine/carboplatin
      chemotherapy. PATIENTS AND METHODS: Thirty-five patients with histologically
      confirmed Stage IIIA/B non-small cell lung cancer were entered into two separate
      sequences, each with multiple cohorts. A dose level was considered acceptable if,
      of the first six eligible patients on each cohort, fewer than three experienced
      dose limiting toxicities. RESULTS: Sequence B of this 2 sequence "ping-pong"
      trial closed early due to toxicity in cohort 2 (gemcitabine 300 mg/m/wk and
      paclitaxel 30 mg/m/wk). On Sequence A, the MTD was the cohort 5 dose: gemcitabine
      450 mg/m/wk and carboplatin 2 area under curve (AUC) concurrently with thoracic
      radiation. Cohort 7 (gemcitabine 600 mg/m/wk and carboplatin 2 AUC) showed 4 dose
      limiting toxicities: 2 grade 3 esophagitis; one grade 3 febrile neutropenia; and
      one grade 4 neutropenia. CONCLUSION: Concurrent gemcitabine/paclitaxel
      chemoradiation regimen followed by adjuvant gemcitabine/carboplatin produced
      excessive toxicity at the lowest tested dose combination and was not suitable for
      further study in this trial. Meanwhile, the MTD of concurrent
      gemcitabine/carboplatin chemoradiation was determined to be gemcitabine 450 mg/m
      and carboplatin AUC-2. This combination was found to be tolerable. Although not a
      primary end point, survival results are summarized as well.

PMID- 19096312
TI  - Bortezomib plus gemcitabine/carboplatin as first-line treatment of advanced non
      small cell lung cancer: a phase II Southwest Oncology Group Study (S0339).
AB  - INTRODUCTION: Bortezomib is a small-molecule proteasome inhibitor with single
      agent activity in patients with non-small cell lung carcinoma (NSCLC) and synergy
      with gemcitabine in preclinical studies. This phase II study of bortezomib in
      combination with gemcitabine/carboplatin was conducted in chemotherapy-naive
      advanced NSCLC patients to assess efficacy and safety. METHODS: Patients with
      selected stage IIIB/IV NSCLC, performance status 0-1, and no history of brain
      metastasis received up to six 21-day cycles of gemcitabine 1000 mg/m, days 1 and
      8, carboplatin area under curve 5.0, day 1, and bortezomib 1.0 mg/m, days 1, 4,
      8, and 11. RESULTS: One-hundred-fourteen patients (52% adenocarcinoma, 85% stage
      IV) received a median of 3.6 treatment cycles. Median follow-up was >3 years.
      Median overall survival was 11 months; 1-year and 2-year survival rates were 47%
      and 19%, respectively. Median progression-free survival was 5 months; 1-year
      progression-free survival rate was 7%. Response rate was 23%, and disease control
      rate (responses + stable disease) was 68%. The most common grade 3/4 toxicities
      were thrombocytopenia (63%) and neutropenia (52%). One patient experienced
      febrile neutropenia. Grade 3/4 neuropathy occurred in 4%, and a further 6%
      experienced grade 2 sensory neuropathy. CONCLUSIONS: Bortezomib plus
      gemcitabine/carboplatin resulted in a notable survival benefit in patients with
      advanced NSCLC, with the anticipated primary toxicity of myelosuppression.
      Further studies designed to investigate the role of bortezomib in advanced NSCLC
      are warranted.

PMID- 19096313
TI  - Pemetrexed in second line and beyond small cell lung cancer: a Hoosier Oncology
      Group phase II study.
AB  - INTRODUCTION: : Small cell lung cancer (SCLC) is initially a chemotherapy
      sensitive disease. Nevertheless, drug-resistance results in disease recurrence in
      most patients. Many drugs, including antimetabolites, are active, but only
      minimal progress has been made in improving survival times for those with
      advanced disease. Based on the need to discover better systemic therapies, we
      conducted a phase II study of pemetrexed in patients with relapsed SCLC. PATIENTS
      AND METHODS: : Eligible patients had SCLC or poorly differentiated neuroendocrine
      cancers of the lung, Eastern Cooperative Oncology Group performance status of 0
      to 2, and had received less than or equal to two prior chemotherapy regimens
      (additional targeted agents were allowed). Both chemotherapy-sensitive (relapse
      >/=90 days from completion of first line therapy) and chemotherapy-resistant
      (progressive disease during or within 90 days from completion of first line
      treatment) patients were eligible and analyzed separately. Pemetrexed was
      administered at 500 mg/m intravenously every 21 days for up to six cycles. All
      patients received folic acid, vitamin B12, and steroid prophylaxis. The primary
      objective of the trial was to estimate the clinical benefit rate (complete plus
      partial response plus stable disease) in each group. RESULTS: : From January 2005
      to September 2005, 20 patients were enrolled in the chemotherapy-sensitive arm
      and 23 patients in the chemotherapy-resistant arm. The majority of patients were
      men, the median age of the two groups were 62.5 and 65, respectively; 75% had a
      performance status of 0 or 1, and more than 50% had received more than one prior
      regimen. Grade 3/4 toxicities were as expected for pemetrexed. Progressive
      disease was the best response in 16 patients (80%) in the chemo-sensitive group
      and 19 patients (83%) in the chemo-refractory group. One patient had a partial
      response and three had stable disease in each group. CONCLUSION: : Pemetrexed has
      minimal single agent activity in relapsed SCLC.

PMID- 19096314
TI  - Phase II study of belinostat (PXD101), a histone deacetylase inhibitor, for
      second line therapy of advanced malignant pleural mesothelioma.
AB  - BACKGROUND: Belinostat (PXD 101) is a novel inhibitor of class I and II histone
      deacetylases. This class of compounds has demonstrated anticancer activity in
      malignant mesothelioma. We conducted a phase II study of belinostat in patients
      with relapsed malignant pleural mesothelioma. METHODS: Patients with advanced
      mesothelioma, progression with one prior chemotherapy regimen and Eastern
      Cooperative Oncology Group performance status 0-2 were eligible. Belinostat was
      administered at 1000 mg/m intravenously over 30 minutes on days 1-5 of every 3
      week cycle. The primary end point was response rate. The Simon two-stage design
      was used. Disease assessments were performed every two cycles. RESULTS: Thirteen
      patients were enrolled. Baseline characteristics were: median age of 73 years;
      Eastern Cooperative Oncology Group performance status 0 (n = 4), 1 (8) and 2 (1).
      A median of two cycles of therapy were administered. Disease stabilization was
      seen in two patients. No objective responses were noted and the study did not
      meet criteria to proceed to the second stage of accrual. Median survival was 5
      months with a median progression-free survival of 1 month. Salient toxicities
      included nausea, emesis, fatigue, and constipation. One patient died as a
      consequence of cardiac arrhythmia which was deemed 'possibly' related to therapy.
      CONCLUSIONS: Belinostat is not active as monotherapy against recurrent malignant
      pleural mesothelioma. Evaluation of combination strategies or alternate dosing
      schedules may be necessary for further development of this novel agent in
      mesothelioma.

PMID- 19096315
TI  - A review of mesothelioma information on the World Wide Web.
AB  - INTRODUCTION: The Internet is a widely used information resource for patients
      with mesothelioma. The goal of this study is to assess the content and quality of
      mesothelioma information presented on the internet using Google as a search
      engine, as well as to test the hypothesis that more popular sites (i.e., higher
      Google rank) are of higher quality. METHODS: The top 100 websites appearing in
      Google using the terms "mesothelioma" were included in the study. Websites were
      evaluated using (a) JAMA benchmarks (authorship, references, currency, and
      disclosure), and (b) an Information score (IS) that awarded websites points (0
      100) for specific information on various aspects of mesothelioma. RESULTS: Of the
      top 100 websites identified, 84 websites were suitable for scoring. Only 5 (6.0%)
      sites met all 4 criteria of the JAMA benchmarks. The mean IS was 23.8 (range, 0
      86). There was a weak but significant positive correlation with Google ranking of
      websites and IS (r = 0.275, p = 0.006). CONCLUSIONS: There is marked variation in
      the quality, integrity, and currency of the information in educational websites
      for mesothelioma patients. Google ranking has shown a weak but significant
      positive correlation to the quality of medical information relating to
      mesothelioma.

PMID- 19096316
TI  - Cystic metastases of papillary thyroid carcinoma mimicking a primary mediastinal
      cyst.

PMID- 19096317
TI  - Unexpected slight fluorodeoxyglucose-uptake on positron emission tomography in a
      pulmonary hamartoma.
AB  - We report the case of a patient with suspected hamartoma with slight
      fluorodeoxyglucose (FDG) uptake on positron emission tomography (PET). Initially,
      follow-up with repeat computed tomography (CT) scan was proposed. Because of the
      risk for retro-obstructive pneumonia, and because there was a small increase in
      diameter of the lesion on CT, thoracotomy was proposed. Pathologic examination
      revealed a surprising and rare finding.

PMID- 19096319
TI  - Thymoma: a focus on current therapeutic management.
AB  - Thymomas are rare intrathoracic malignant tumors. Commonly used staging system is
      the Masaoka classification, based on peroperative and histopathological findings.
      Surgery is the cornerstone of the management of thymomas, initially being useful
      for precise histopathological diagnosis and staging, and in most cases ensuring
      the first step of the therapeutics simultaneously. After tumor stage, complete
      resection is the most constant and significant prognostic factor for progression
      free and overall survival. Postoperative radiotherapy is recommended in
      incompletely resected thymomas. Completely resected stage II and III tumors may
      also benefit from adjuvant radiotherapy to reduce local recurrence rates but
      without impact on survival. In primary unresectable thymomas, multimodal strategy
      nowadays includes neoadjuvant chemotherapy, extensive surgery, adjuvant
      radiotherapy, and in some cases, adjuvant chemotherapy. The most popular
      chemotherapy regimens combine cisplatin, adriamycin, etoposide, cyclophophamide,
      or ifosfamide.The management of thymomas is a paradigm of cooperation between
      clinicians, surgeons, and pathologists from establishing the diagnosis to
      organizing the therapeutic strategy and evaluating the prognosis. As a
      consequence of their rarity, no prospective randomized trials are available and
      collaborative studies are warranted to evaluate and improve current therapeutic
      standards, taking into account recent improvements in techniques, such as robotic
      surgery, radiotherapy, and supportive treatments.

PMID- 19096318
TI  - Clinical impact of high-throughput gene expression studies in lung cancer.
AB  - Lung cancer is the leading cause of cancer death in the United States and the
      world. The high mortality rate results, in part, from the lack of effective tools
      for early detection and the inability to identify subsets of patients who would
      benefit from adjuvant chemotherapy or targeted therapies. The development of high
      throughput genome-wide technologies for measuring gene expression, such as
      microarrays, have the potential to impact the mortality rate of lung cancer
      patients by improving diagnosis, prognosis, and treatment. This review will
      highlight recent studies using high-throughput gene expression technologies that
      have led to clinically relevant insights into lung cancer. The hope is that
      diagnostic and prognostic biomarkers that have been developed as part of this
      work will soon be ready for wide-spread clinical application and will have a
      dramatic impact on the evaluation of patients with suspect lung cancer, leading
      to effective personalized treatment regimens.

PMID- 19096320
TI  - Detection of an asymptomatic right-ventricle cardiac metastasis from a small-cell
      lung cancer by F-18-FDG PET/CT.
AB  - A right heart metastasis of a small-cell lung cancer was found on the whole-body
      F-fluoro-deoxy-glucose positron emission tomography/computed tomography (F-FDG
      PET/CT) of a 69-year-old smoker investigated for a right pulmonary mass
      discovered on chest radiography after a fracture of the right humerus. The PET
      scan showed an increased FDG uptake by the mass in the right lung and an intense,
      atypical focal activity of the right ventricle strongly suggestive of a
      neoplastic process. CT-guided lung biopsy revealed a small-cell lung cancer and
      myocardial biopsy confirmed the presence of a cardiac metastasis. The patient was
      treated with six cycles of chemotherapy followed by radiation therapy, which
      included the heart lesion. At follow-up PET/CT 2 months after the end of
      treatment, the abnormal cardiac uptake had disappeared, whereas increased FDG
      uptake persisted in the pulmonary residual mass.

PMID- 19096321
TI  - The port site recurrence after a thoracoscopic and video-assisted esophagectomy
      for advanced esophageal cancer.
AB  - INTRODUCTION: Thoracoscopic or video-assisted thoracic esophagectomies have been
      performed for the last 10 years. Nevertheless, some reports have showed a risk of
      dissemination with endoscopic or video-assisted surgery for malignant disease.
      This institute experienced three cases of port site recurrence after a
      thoracoscopic esophagectomy for advanced esophageal cancer. Following those
      cases, induction chemo-radiation therapy was performed for patient with advanced
      esophageal cancer before thoracoscopic or video-assisted esophagectomy. Since
      introducing induction chemo-radiation therapy, no patients have experienced port
      site recurrence after a thoracoscopic or video-assisted esophagectomy for
      advanced esophageal cancer. In this study, the two patients groups are compared
      before and after the introduction of induction chemo-radiation therapy. PATIENTS
      AND METHODS: Between November 1995 and December 2005, thoracoscopic and video
      assisted esophagectomies were performed on 112 (72.7%) patients out of 154 who
      underwent a surgical resection for thoracic and abdominal esophageal cancer. The
      histologic type of cancer was squamous cell carcinoma in 109 (97.4%) patients and
      adenocarcinoma in 3 (2.6%). Ninety-one patients were men and 21 were women. The
      tumor was located in the upper thoracic esophagus in 22 (19.6%) patients, the
      middle thoracic esophagus in 49 (43.8%), the lower thoracic esophagus in 34
      (30.4%), and the abdominal esophagus in 7 (6.2%). RESULTS: Before December 1999,
      port site recurrence occurred in three cases of those of 29 patients with
      clinical T2-T4 esophageal cancer from 3 to 6 months after surgery, and pleural
      dissemination was observed in two of those patients. Since January 2000,
      induction chemo-radiation therapy (low-dose fluorouracil and platinum + 40 Gy
      radiation) has been performed to 31 patients with clinical T2-T4 disease, and
      port site recurrence has not occurred in any patients who received trimodality
      therapy. CONCLUSIONS: We think that the trend toward less port site recurrences
      with induction therapy should be examined in future studies of video-assisted
      thoracic surgery esophagectomy to confirm our findings.

PMID- 19096322
TI  - Malignant triton tumor of the brachial plexus invading the left thoracic inlet: a
      rare differential diagnosis of pancoast tumor.
AB  - Malignant triton tumor is a divergent malignant peripheral nerve sheath tumor
      with rhabdomyoblastic differentiation. We report a case of malignant triton tumor
      arising in the brachial plexus of a 28-year-old women with neurofibromatosis type
      1. Fluorodeoxyglucose-positron emission tomography-computed tomography before
      excision demonstrated a tumor with a maximum standard uptake value of 21 at 4
      hours postinjection. The patient underwent complete excision of the tumor through
      median sternotomy and left supraclavicular approach. Adjuvant radiotherapy and
      chemotherapy were planned but the patient died of metastatic disease within 3
      months of surgical resection.

PMID- 19096323
TI  - Erlotinib combined with cyclosporine in a liver-transplant recipient with
      epidermal growth factor receptor-mutated non-small cell lung cancer.

PMID- 19096324
TI  - Germ-line and somatic presentations of the EGFR T790M mutation in lung cancer.

PMID- 19096325
TI  - Complete response of recurrent squamous cell carcinoma of the lung: dose the dose
      matter?

PMID- 19096326
TI  - Wood-smoke exposure (WSE) as a predictor of response and survival in erlotinib
      treated non-small cell lung cancer (NSCLC) patients.

PMID- 19096327
TI  - Current approach to treatment of non-small cell lung cancer in developing
      countries--time for a rethink?

PMID- 19096352
TI  - To intubate or not to intubate at birth, this is still the question! Will
      experimental studies give us the answer?: commentary on the article by Polglase
      et al. on page 67.

PMID- 19096353
TI  - Mitochondrial energy production correlates with the age-related BMI.
AB  - Besides characteristic neurologic and musculoskeletal symptoms, children with
      mitochondrial dysfunction often present with feeding problems and failure to
      thrive. Substrate depletion for the respiratory chain has an effect on energy
      expenditure. Secondary mitochondrial dysfunction has been reported in severe
      chronic malnutrition. We evaluated the nutritional state, the growth parameters,
      and the metabolic condition in 172 children undergoing muscle biopsy for a
      suspected disorder of the oxidative phosphorylation system (OXPHOS). We performed
      dietary evaluation and initiated nutritional intervention when needed before the
      biopsy. Mitochondrial dysfunction was confirmed by detection of enzyme-complex
      deficiencies and/or by mutations in 83 children, in 14 patients no biochemical
      abnormalities were found. In the whole study group, and in the subgroup with
      enzyme-complex deficiency and/or mutation, a significant correlation was found
      between the mitochondrial production of adenosine triphosphate (ATP) and the age
      related body mass index (BMI). Nutritional state and growth should be considered
      by interpreting the results of ATP-production in fresh muscle biopsy. Because of
      a positive correlation between the age-appropriate BMI and the ATP-production, we
      strongly advise optimizing the nutritional state preceding the muscle biopsy in
      children with a suspected OXPHOS-disorder. Dietary intervention remains although
      challenging because of frequent gastrointestinal problems and eating disorders.

PMID- 19096355
TI  - I read with great interest the article by Hafkamp et al.

PMID- 19096356
TI  - Traffic-generated air pollution and myocardial infarction.
AB  - BACKGROUND: Although long-term air pollution exposure has been linked to
      cardiovascular mortality, data on incidence and nonfatal coronary disease are
      limited and inconclusive. The aim of this study was to investigate the
      association between long-term residential exposure to air pollution from traffic
      and the risk of nonfatal and fatal myocardial infarction. METHODS: The records of
      all individuals aged 15 to 79 with a first event of myocardial infarction in
      Stockholm County during 1985 to 1996 were retrieved from a registry. Population
      controls were randomly selected from the study base stratified by age, sex, and
      calendar year. Individual socioeconomic data and home addresses were obtained
      from population censuses 1970 to 1995. Annual air pollution exposure was assessed
      by dispersion modeling at the home addresses of 24,347 cases and 276,926
      controls. RESULTS: Five-year average traffic-generated air pollution exposure
      corresponding to a difference in nitrogen dioxide from the fifth to the 95th
      percentile (31 microg/m) was associated with an odds ratio for fatal myocardial
      infarction adjusted for age, sex, calendar year, and socioeconomic status of 1.23
      (95% confidence interval [CI] = 1.15-1.32). The corresponding odds ratio was 2.54
      (1.96-3.29) among those with least expected misclassification of true individual
      exposure (those who did not move between censuses). Different time-windows and
      analyses of other pollutants including carbon monoxide and particles less than 10
      mum in diameter (PM10) produced weaker associations. There was no increased risk
      for nonfatal myocardial infarction (ORs 0.94-0.98). CONCLUSIONS: Long-term
      exposure to traffic-generated air pollution is associated with fatal myocardial
      infarction but not with nonfatal infarction.

PMID- 19096357
TI  - The effect of Web-based Braden Scale training on the reliability of Braden
      subscale ratings.
AB  - PURPOSE: The primary purpose of this study was to evaluate the effect of Web
      based Braden Scale training on the reliability of Braden Scale subscale ratings
      made by nurses working in acute care hospitals. A secondary purpose was to
      describe the distribution of reliable Braden subscale ratings before and after
      Web-based Braden Scale training. DESIGN: Secondary analysis of data from a
      recently completed quasi-experimental, pretest-posttest, interrater reliability
      study. SUBJECTS AND SETTING: A convenience sample of RNs working at 3 Michigan
      medical centers voluntarily participated in the study. RN participants included
      nurses who used the Braden Scale regularly at their place of employment ("regular
      users") as well as nurses who did not use the Braden Scale at their place of
      employment ("new users"). METHODS: Using a pretest-posttest, quasi-experimental
      design, pretest interrater reliability data were collected to identify the
      percentage of nurses making reliable Braden subscale assessments. Nurses then
      completed a Web-based Braden Scale training module after which posttest
      interrater reliability data were collected. The reliability of nurses' Braden
      subscale ratings was determined by examining the level of agreement/disagreement
      between ratings made by an RN and an "expert" rating the same patient. In total,
      381 RN-to-expert dyads were available for analysis. RESULTS: During both the
      pretest and posttest periods, the percentage of reliable subscale ratings was
      highest for the activity subscale, lowest for the moisture subscale, and second
      lowest for the nutrition subscale. With Web-based Braden Scale training, the
      percentage of reliable Braden subscale ratings made by new users increased for
      all 6 subscales with statistically significant improvements in the percentage of
      reliable assessments made on 3 subscales: sensory-perception, moisture, and
      mobility. Training had virtually no effect on the percentage of reliable subscale
      ratings made by regular users of the Braden Scale. CONCLUSION: With Web-based
      Braden Scale training the percentage of nurses making reliable ratings increased
      for all 6 subscales, but this was true for new users only. Additional research is
      needed to identify educational approaches that effectively improve and sustain
      the reliability of subscale ratings among regular users of the Braden Scale.
      Moreover, special attention needs to be given to ensuring that all nurses working
      with the Braden Scale have a clear understanding of the intended meanings and
      correct approaches to rating moisture and nutrition subscales.

PMID- 19096358
TI  - Development and psychometric evaluation of the Ostomy Adjustment Inventory-23.
AB  - PURPOSE: This article describes the development of the Ostomy Adjustment
      Inventory-23 (OAI-23), a self-report, multidimensional scale designed to assess
      psychosocial adjustment in patients with ostomy. SUBJECTS AND SETTING: Five
      hundred seventy persons with a colostomy, ileostomy, or urostomy, who were
      randomly selected from 3 national databases, provided assessable data. RESULTS:
      The results indicate that the OAI-23 is reliable (the Cronbach alpha = .93, split
      half = 0.91, and test-retest (r) = 0.83) and valid, correlating positively with
      Felton's Acceptance of Illness Scale (r = 0.72) and confirming expected
      improvements in adjustment consistent with increasing time since surgery (F 5,531
      = 5.22, P < .001). Four factors (eigenvalue >or= 1) that accounted for 55.4% of
      the total variance emerged from factor analysis. CONCLUSION: The OAI-23 is a
      valid and reliable measure of psychosocial adjustment that will be of interest to
      both researchers investigating life after stoma surgery and clinicians making
      objective assessments of their patients' progress.

PMID- 19096359
TI  - Analysis of pairwise cell interactions using an integrated dielectrophoretic
      microfluidic system.
AB  - Blood vessel formation, during either normal vascular reconstruction or
      pathogenic tumour formation, relies upon highly organized cell-cell interactions.
      Isolating the function of any particular component of this cell-cell
      communication is often difficult, given the vast complexity of communication
      networks in multicellular systems. One way to address this problem is to analyse
      cell-cell communication on the most elementary scale--cell pairs. Here, we
      describe an integrated dielectrophoretic (DEP)-microfluidic device allowing for
      such analysis. Single cancer and endothelial cells (ECs) and cell pairs were
      patterned using DEP force and cultured within a minimally stressful microfluidic
      channel network. Controlling both the initial cell positions and extracellular
      environment, we investigated cell motility in homo- and heterotypic cell pairs
      under diverse conditions. We found that secreted collagen IV and soluble vascular
      endothelial growth factor have considerable guidance effect on ECs at the level
      of two interacting cells. Cell interaction rules extracted from the experiments
      of cell pairs were used to mathematically predict branching patterns
      characteristic of developing multicellular blood vessels. This integrative
      analysis method can be extended to other systems involving complex multicellular
      interactions.

PMID- 19096360
TI  - Metabolomic and flux-balance analysis of age-related decline of hypoxia tolerance
      in Drosophila muscle tissue.
AB  - The fruitfly Drosophila melanogaster is increasingly used as a model organism for
      studying acute hypoxia tolerance and for studying aging, but the interactions
      between these two factors are not well known. Here we show that hypoxia tolerance
      degrades with age in post-hypoxic recovery of whole-body movement, heart rate and
      ATP content. We previously used (1)H NMR metabolomics and a constraint-based
      model of ATP-generating metabolism to discover the end products of hypoxic
      metabolism in flies and generate hypotheses for the biological mechanisms. We
      expand the reactions in the model using tissue- and age-specific microarray data
      from the literature, and then examine metabolomic profiles of thoraxes after 4 h
      at 0.5% O(2) and after 5 min of recovery in 40- versus 3-day-old flies. Model
      simulations were constrained to fluxes calculated from these data. Simulations
      suggest that the decreased ATP production during reoxygenation seen in aging
      flies can be attributed to reduced recovery of mitochondrial respiration pathways
      and concomitant overdependence on the acetate production pathway as an energy
      source.

PMID- 19096361
TI  - Robust and sensitive control of a quorum-sensing circuit by two interlocked
      feedback loops.
AB  - The quorum-sensing (QS) response of Vibrio fischeri involves a rapid switch
      between low and high induction states of the lux operon over a narrow
      concentration range of the autoinducer (AI) 3-oxo-hexanoyl-L-homoserine lactone.
      In this system, LuxR is an AI-dependent positive regulator of the lux operon,
      which encodes the AI synthase. This creates a positive feedback loop common in
      many bacterial species that exhibit QS-controlled gene expression. Applying a
      combination of modeling and experimental analyses, we provide evidence for a LuxR
      autoregulatory feedback loop that allows LuxR to increase its concentration in
      the cell during the switch to full lux activation. Using synthetic lux gene
      fragments, with or without the AI synthase gene, we show that the buildup of LuxR
      provides more sensitivity to increasing AI, and promotes the induction process.
      Elevated LuxR levels buffer against spurious variations in AI levels ensuring a
      robust response that endows the system with enhanced hysteresis. LuxR
      autoregulation also allows for two distinct responses within the same cell
      population.

PMID- 19096362
TI  - Functional specialization of transcription elongation factors.
AB  - Elongation factors NusG and RfaH evolved from a common ancestor and utilize the
      same binding site on RNA polymerase (RNAP) to modulate transcription. However,
      although NusG associates with RNAP transcribing most Escherichia coli genes, RfaH
      regulates just a few operons containing ops, a DNA sequence that mediates RfaH
      recruitment. Here, we describe the mechanism by which this specificity is
      maintained. We observe that RfaH action is indeed restricted to those several
      operons that are devoid of NusG in vivo. We also show that RfaH and NusG compete
      for their effects on transcript elongation and termination in vitro. Our data
      argue that RfaH recognizes its DNA target even in the presence of NusG. Once
      recruited, RfaH remains stably associated with RNAP, thereby precluding NusG
      binding. We envision a pathway by which a specialized regulator has evolved in
      the background of its ubiquitous paralogue. We propose that RfaH and NusG may
      have opposite regulatory functions: although NusG appears to function in concert
      with Rho, RfaH inhibits Rho action and activates the expression of poorly
      translated, frequently foreign genes.

PMID- 19096363
TI  - TGFbeta-stimulated Smad1/5 phosphorylation requires the ALK5 L45 loop and
      mediates the pro-migratory TGFbeta switch.
AB  - During the course of breast cancer progression, normally dormant tumour-promoting
      effects of transforming growth factor beta (TGFbeta), including migration,
      invasion, and metastasis are unmasked. In an effort to identify mechanisms that
      regulate the pro-migratory TGFbeta 'switch' in mammary epithelial cells in vitro,
      we found that TGFbeta stimulates the phosphorylation of Smad1 and Smad5, which
      are typically associated with bone morphogenetic protein signalling.
      Mechanistically, this phosphorylation event requires the kinase activity and,
      unexpectedly, the L45 loop motif of the type I TGFbeta receptor, ALK5, as
      evidenced by studies using short hairpin RNA-resistant ALK5 mutants in ALK5
      depleted cells and in vitro kinase assays. Functionally, Smad1/5 co-depletion
      studies demonstrate that this phosphorylation event is essential to the
      initiation and promotion of TGFbeta-stimulated migration. Moreover, this
      phosphorylation event is preferentially detected in permissive environments such
      as those created by tumorigenic cells or oncogene activation. Taken together, our
      data provide evidence that TGFbeta-stimulated Smad1/5 phosphorylation, which
      occurs through a non-canonical mechanism that challenges the notion of selective
      Smad phosphorylation by ALK5, mediates the pro-migratory TGFbeta switch in
      mammary epithelial cells.

PMID- 19096364
TI  - Neurite consolidation is an active process requiring constant repression of
      protrusive activity.
AB  - During development, neurons extend projections that pathfind to reach their
      appropriate targets. These projections are composed of two distinct domains: a
      highly dynamic growth cone and a stable neurite shaft, which is considered to be
      consolidated. Although the regulation of these domains is critical to the
      appropriate formation of neural networks, the molecular mechanisms that regulate
      neurite shape remain poorly understood. Here, we show that calpain protease
      activity localizes to the neurite shaft, where it is essential for the repression
      of protrusive activity by limiting cortactin levels and inhibiting actin
      polymerization. Correspondingly, inhibition of calpain by branching factors
      induces the formation of new growth cones along the neurite shaft through cAMP
      elevation. These findings demonstrate that neurite consolidation is an active
      process requiring constant repression of protrusive activity. We also show that
      sprouting is, at least in part, accomplished by turning off the mechanism of
      consolidation.

PMID- 19096365
TI  - Structure of the transcriptional regulator LmrR and its mechanism of multidrug
      recognition.
AB  - LmrR is a PadR-related transcriptional repressor that regulates the production of
      LmrCD, a major multidrug ABC transporter in Lactococcus lactis. Transcriptional
      regulation is presumed to follow a drug-sensitive induction mechanism involving
      the direct binding of transporter ligands to LmrR. Here, we present crystal
      structures of LmrR in an apo state and in two drug-bound states complexed with
      Hoechst 33342 and daunomycin. LmrR shows a common topology containing a typical
      beta-winged helix-turn-helix domain with an additional C-terminal helix involved
      in dimerization. Its dimeric organization is highly unusual with a flat-shaped
      hydrophobic pore at the dimer centre serving as a multidrug-binding site. The
      drugs bind in a similar manner with their aromatic rings sandwiched in between
      the indole groups of two dimer-related tryptophan residues. Multidrug recognition
      is facilitated by conformational plasticity and the absence of drug-specific
      hydrogen bonds. Combined analyses using site-directed mutagenesis, fluorescence
      based drug binding and protein-DNA gel shift assays reveal an allosteric coupling
      between the multidrug- and DNA-binding sites of LmrR that most likely has a
      function in the induction mechanism.

PMID- 19096366
TI  - Lifestyle modification counseling for hypertensive patients: results from the
      National Health and Nutrition Examination Survey 1999-2004.
AB  - BACKGROUND: Lifestyle modification is recommended for all patients with the
      diagnosis of hypertension. METHODS: We examined 3,497 adult hypertensive
      participants (representing 42 million Americans), from the National Health and
      Nutrition Examination Survey (NHANES) 1999-2004. We analyzed the rate,
      demographic, and clinical factors of participants who reported receiving
      lifestyle counseling and their adherence. RESULTS: Of the 3,497 participants with
      hypertension, 84% reported receiving lifestyle modification counseling. After
      adjustment for demographic and clinical characteristics, non-Hispanic blacks were
      more likely to report receiving counseling (odds ratio (OR), 2.5; P < 0.001) when
      compared to whites. Men (OR, 1.5; P = 0.02) reported receiving counseling more
      often than women as well as those with Medicare insurance (OR, 1.5; P = 0.02)
      compared to the privately insured. Participants who were hypercholesterolemic
      (OR, 1.7; P < 0.001), diabetic (OR, 3.5; P < 0.001), overweight (OR, 1.5; P <
      0.001), or obese (OR 3.0; P < 0.001) reported receiving lifestyle counseling more
      often than those without these conditions. Of those receiving counseling, 88%
      reported adhering to those recommendations. After adjustment for demographic and
      clinical characteristics, only non-Hispanic blacks (OR, 2.8; P < 0.001) and those
      aged >60 (OR, 1.9; P = 0.04) were more likely to report adhering when advised.
      CONCLUSIONS: High cardiovascular risk hypertensive patients had high rates of
      lifestyle counseling. However, gaps exist in lifestyle counseling for young and
      low cardiovascular risk hypertensive patients. In addition, differences in rates
      of adherence exist especially in those with high cardiovascular risk comorbid
      conditions. Future work is needed to increase adherence to lifestyle counseling
      for all hypertensive patients.

PMID- 19096367
TI  - Polydendrocytes (NG2 cells): multifunctional cells with lineage plasticity.
AB  - NG2 cells (also known as polydendrocytes) are a population of CNS cells that are
      distinct from neurons, mature oligodendrocytes, astrocytes and microglia. They
      can be identified by the expression of the proteoglycan NG2, have a highly
      branched morphology and are distributed throughout the grey and white matter.
      They differentiate into oligodendrocytes in vitro and have often been equated
      with oligodendrocyte precursor cells. However, whether polydendrocytes are
      multipotential cells that can give rise to neurons and astrocytes as well as
      oligodendrocytes is now highly debated. Furthermore, electrophysiological studies
      indicate that polydendrocytes receive synaptic input from neurons, suggesting
      that they are integrated in the neural network. This Review highlights recent
      findings and unresolved questions related to the lineage and function of
      polydendrocytes in the CNS.

PMID- 19096369
TI  - How do you feel--now? The anterior insula and human awareness.
AB  - The anterior insular cortex (AIC) is implicated in a wide range of conditions and
      behaviours, from bowel distension and orgasm, to cigarette craving and maternal
      love, to decision making and sudden insight. Its function in the re
      representation of interoception offers one possible basis for its involvement in
      all subjective feelings. New findings suggest a fundamental role for the AIC (and
      the von Economo neurons it contains) in awareness, and thus it needs to be
      considered as a potential neural correlate of consciousness.

PMID- 19096371
TI  - Functional specialization in the supplementary motor complex.

PMID- 19096368
TI  - Pathological and protective roles of glia in chronic pain.
AB  - Glia have emerged as key contributors to pathological and chronic pain
      mechanisms. On activation, both astrocytes and microglia respond to and release a
      number of signalling molecules, which have protective and/or pathological
      functions. Here we review the current understanding of the contribution of glia
      to pathological pain and neuroprotection, and how the protective, anti
      inflammatory actions of glia are being harnessed to develop new drug targets for
      neuropathic pain control. Given the prevalence of chronic pain and the partial
      efficacy of current drugs, which exclusively target neuronal mechanisms, new
      strategies to manipulate neuron-glia interactions in pain processing hold
      considerable promise.

PMID- 19096372
TI  - Treatment of hypertension: a failing report card.

PMID- 19096373
TI  - Blood pressure variability remains an elusive predictor of cardiovascular
      outcome.

PMID- 19096375
TI  - Children, obesity, and high blood pressure: Asian populations at high risk.

PMID- 19096376
TI  - Deletion of the alpha-8 integrin gene does not protect mice from myocardial
      fibrosis in DOCA hypertension.

PMID- 19096377
TI  - Strengthening the case for global risk assessment of patients with high blood
      pressure.

PMID- 19096378
TI  - Critique of "The influence of gender on the association of alcohol drinking with
      blood pressure".

PMID- 19096379
TI  - Inverse associations between androgens and renal function: the Young Men
      Cardiovascular Association (YMCA) study.
AB  - BACKGROUND: Men exhibit higher risk of nondiabetic renal diseases than women.
      This male susceptibility to renal disease may be mediated by gender-specific
      factors such as sex hormones. METHODS: We have undertaken a cross-sectional
      examination of associations between renal function (creatinine clearance
      estimated based on Cockcroft-Gault equation) and circulating levels of sex
      steroids (total testosterone, total estradiol, estrone, androstenedione,
      dehydroepiandrosterone sulfate (DHEA-S), and dihydrotestosterone) in 928 young
      (mean age: 18.5 +/- 1.2 years) men. RESULTS: Both androstenedione and DHEA-S
      showed inverse linear associations with renal function in the crude analysis of
      lean men (those with body mass index (BMI) less than median). However, only DHEA
      S retained its association with renal function in lean subjects after adjustment-
      assuming no changes in other independent variables 1 s.d. increase in DHEA-S was
      associated with 13%-s.d. decrease in creatinine clearance (P = 0.004).
      Testosterone decreased across tertiles of creatinine clearance only in the crude
      analysis of nonlean (BMI greater than median) subjects (P < 0.001). The adjusted
      regression analysis that assumed no changes in other independent variables showed
      that 1 s.d. increase in total testosterone was associated with 11%-s.d. decrease
      in creatinine clearance of nonlean men (P = 0.006). Factor analysis confirmed an
      inverse association of renal function with both sex steroids and a different
      pattern of their loadings on glomerular filtration-related factors in lean (DHEA
      S) and nonlean (testosterone) subjects. CONCLUSIONS: Our data may suggest that
      androgens are inversely associated with estimated renal function in apparently
      healthy men without history of cardiovascular disease.

PMID- 19096381
TI  - Innovation, innovation, innovation.
AB  - The financial crisis teaches us about the consequences of ignoring risks. We
      cannot afford to repeat the same mistakes for the continuing crises in energy and
      climate.

PMID- 19096382
TI  - Investing in the future. Interview by Joerg Heber.
AB  - Joseph Michels, a managing director at One Equity Partners, talks to Nature
      Materials about making private equity investments in high-tech companies in times
      of recession.

PMID- 19096384
TI  - Optoelectronics: Combining chemical worlds.

PMID- 19096385
TI  - Quantum dots: Squeeze or stretch?

PMID- 19096386
TI  - Ferroelectrics: Start the presses.

PMID- 19096380
TI  - Drug development from marine natural products.
AB  - Drug discovery from marine natural products has enjoyed a renaissance in the past
      few years. Ziconotide (Prialt; Elan Pharmaceuticals), a peptide originally
      discovered in a tropical cone snail, was the first marine-derived compound to be
      approved in the United States in December 2004 for the treatment of pain. Then,
      in October 2007, trabectedin (Yondelis; PharmaMar) became the first marine
      anticancer drug to be approved in the European Union. Here, we review the history
      of drug discovery from marine natural products, and by describing selected
      examples, we examine the factors that contribute to new discoveries and the
      difficulties associated with translating marine-derived compounds into clinical
      trials. Providing an outlook into the future, we also examine the advances that
      may further expand the promise of drugs from the sea.

PMID- 19096387
TI  - Drug delivery: Stealth particles give mucus the slip.

PMID- 19096388
TI  - Material witness: nature versus naturoid.

PMID- 19096389
TI  - Physical approaches to biomaterial design.
AB  - The development of biomaterials for drug delivery, tissue engineering and medical
      diagnostics has traditionally been based on new chemistries. However, there is
      growing recognition that the physical as well as the chemical properties of
      materials can regulate biological responses. Here, we review this transition with
      regard to selected physical properties including size, shape, mechanical
      properties, surface texture and compartmentalization. In each case, we present
      examples demonstrating the significance of these properties in biology. We also
      discuss synthesis methods and biological applications for designer biomaterials,
      which offer unique physical properties.

PMID- 19096390
TI  - Regulation of T-helper-cell lineage development by osteopontin: the inside story.
AB  - Studies of osteopontin (OPN)-dependent regulation of immune responses have
      focused on the cytokine activities of the secreted form of this protein. Recent
      evidence has revealed that an intracellular form of OPN expressed by dendritic
      cells regulates the expression of pro-inflammatory cytokines and the
      differentiation of T helper (T(H))-cell lineages. In this Opinion article, we
      discuss the properties of both OPN isoforms and their respective contributions to
      the immune response. We propose that cell-type-specific expression of secreted
      and intracellular OPN regulates the development of distinct effector T(H) cells,
      including that of T(H)1 and T(H)17 cells.

PMID- 19096391
TI  - Mitotic catastrophe is the predominant response to histone acetyltransferase
      depletion.
AB  - Histone acetylation induces chromatin opening by perturbing higher-order
      chromatin compaction and folding, suggesting that histone acetylation and
      deacetylation dynamics are central to chromosome condensation or decondensation.
      The condensation of chromosomes during mitosis is an essential prerequisite for
      successful chromosome segregation. In this study, we depleted three
      representative histone acetyltransferases (HATs; p300, CBP, and P/CAF) using
      shRNAs to explore their role in regulating mitotic progression and chromosome
      segregation. We showed that HAT depletion severely interfered with the normal
      timing of mitotic progression, and it reduced condensin subunit levels. The
      predominant response to HAT depletion, in both human primary and cancer cells,
      was a mitotic catastrophe following aberrant mitotic arrest. Alternatively,
      adaptation to HAT depletion, particularly in cancer cells, led to multinucleation
      and aneuploidy. Interestingly, mitotic catastrophe induced by HAT depletion
      appeared to be coupled to the signaling process of H2AX phosphorylation and foci
      formation, independently of DNA double-strand breaks and DNA damage. Taken
      together, our results provide novel molecular evidence that HAT proteins maintain
      mitotic chromatin assembly and integrity as a cellular determinant of mitotic
      cell death.

PMID- 19096392
TI  - IEX-1 targets mitochondrial F1Fo-ATPase inhibitor for degradation.
AB  - IEX-1 (Immediate Early response gene X-1) is a stress-inducible gene. It
      suppresses production of reactive oxygen species (ROS) and protects cells from
      apoptosis induced by a wide range of stimuli, but the underlying mechanism is not
      known. This study reveals that IEX-1 targets the mitochondrial F1Fo-ATPase
      Inhibitor (IF1) for degradation, resulting in acceleration of ATP hydrolysis,
      concomitant with reduction in ROS production. A prominent role for IF1
      degradation in the function of IEX-1 was corroborated by siRNA-mediated gene
      silencing of IF1 that recapitulated the effects of IEX-1 on ATP hydrolysis and
      ROS production. Moreover, progressive C-terminal truncation studies demonstrated
      that IEX-1 interacted with the C terminus of IF1 and the interaction might render
      IF1 prone to degradation by an as yet unidentified mitochondrial protease. In
      support of a physiological importance of IEX-1 in the modulation of IF1
      expression, gene-targeted deletion of IEX-1 stabilized IF1 and reduced
      mitochondrial F1Fo-ATPase activity in vivo. The altered activity of the F1Fo
      enzyme may account for a metabolic switch from oxidative phosphorylation toward
      glycolysis in IEX-1 deficient cells. Thus, IEX-1 deficient cells were more
      susceptible to glucose deprivation than wild type counterparts and displayed
      increased glucose uptake and lactate production in hypoxic conditions. The cells
      were also relatively refractory to oligomycin-mediated inhibition of ATP
      production. The studies offer novel insights into the primary role of IEX-1 in
      regulating a balance between energy provision and ROS production.

PMID- 19096395
TI  - Lessons learned from lung cancer chemoprevention trials.

PMID- 19096394
TI  - Sentinel node biopsy needs for a suitable therapeutic management of the cutaneous
      melanoma.

PMID- 19096393
TI  - Polarized fluid movement and not cell death, creates luminal spaces in adult
      prostate epithelium.
AB  - There are two predominant theories for lumen formation in tissue morphogenesis:
      cavitation driven by cell death, and membrane separation driven by epithelial
      polarity. To define the mechanism of lumen formation in prostate acini, we
      examined both theories in several cell lines grown in three-dimensional (3D)
      Matrigel culture. Lumen formation occurred early in culture and preceded the
      expression of cell death markers for apoptosis (active caspase 3) and autophagy
      (LC-3). Active caspase 3 was expressed by very few cells and inhibition of
      apoptosis did not suppress lumen formation. Despite LC-3 expression in all cells
      within a spheroid, this was not associated with cell death. However, expression
      of a prostate-secretory protein coincided with lumen formation and subsequent
      disruption of polarized fluid movement led to significant inhibition of lumen
      formation. This work indicates that lumen formation is driven by the polarized
      movement of fluids and proteins in 3D prostate epithelial models and not by
      cavitation.

PMID- 19096396
TI  - Sunitinib is superior to interferon alpha with respect to quality of life for
      patients with renal cell carcinoma.
AB  - Randomized trials have shown that both anti-vascular endothelial growth factor
      (VEGF) therapy and inhibition of the mammalian target of rapamycin have superior
      clinical efficacy when compared with interferon alpha in the first-line treatment
      of advanced renal cell carcinoma. In 2007, a pivotal phase III trial randomly
      allocated 750 patients with advanced renal cell carcinoma to receive either the
      VEGF-receptor tyrosine kinase inhibitor sunitinib or interferon alpha, and showed
      that sunitinib led to improved response rates, progression-free and overall
      survival. In this Practice Point, we discuss the data reported by Cella et al.,
      which showed that the quality of life of patients in this trial was better with
      sunitinib than interferon alpha; these differences were predominantly due to
      better control of disease-related symptoms by sunitinib. This landmark study is
      the first to report comparative quality-of-life data for an anti-VEGF therapy and
      a cytokine therapy.

PMID- 19096398
TI  - Dammed if you don't.

PMID- 19096399
TI  - Golden additions.

PMID- 19096400
TI  - Lost file?

PMID- 19096401
TI  - Relevant criteria.

PMID- 19096402
TI  - A double molar.

PMID- 19096403
TI  - Let's face it.

PMID- 19096404
TI  - Bidi tobacco.

PMID- 19096405
TI  - Swabbing for accuracy.

PMID- 19096423
TI  - A study of patients attending a multidisciplinary hypodontia clinic over a five
      year period.
AB  - AIM: To gather information about planned treatment, outcomes and type of patient
      attending a multidisciplinary hypodontia clinic over a five year period at
      Glasgow Dental Hospital and School. STUDY DESIGN: There were three parts to the
      study: (i) to report demographics of the patients with hypodontia attending the
      multidisciplinary clinic from its outset in February 2002 until February 2007;
      (ii) to report on both the treatment planned on the clinic and whether this was
      completed as intended; and (iii) to show the number of patients for whom implants
      were considered. METHODS: The existing hypodontia database was analysed,
      supplemented where required by data gathered retrospectively from patients'
      clinical records and radiographs. RESULTS: In the demographic component there
      were 108 patients seen between February 2002 and February 2007, 57% female
      patients with a mean age of 13 years. Ninety-one percent (n = 107) of patients
      were missing two or more teeth, with the most common missing teeth being upper
      lateral incisors. Orthodontic therapy was most frequently considered in treatment
      planning. Nineteen patients (23%) may require dental implants. CONCLUSIONS: The
      majority of the patients were female, adolescent and had a positive or suspected
      family history of hypodontia. Orthodontic therapy was most frequently considered
      in treatment planning. Nineteen patients may undergo surgery for placement of
      dental implants.

PMID- 19096443
TI  - Nanoparticle delivery of anti-metastatic NM23-H1 gene improves chemotherapy in a
      mouse tumor model.
AB  - Gene therapy provides a promising approach for cancer treatment. Earlier studies
      suggested that poly-L-lysine-modified iron oxide nanoparticles (IONP-PLL) might
      be a promising gene delivery system that can transfect DNA efficiently in vitro
      and in vivo. In this study we used IONP-PLL as gene carriers to deliver the NM23
      H1 gene, the first suppressor gene of cancer metastasis, to tumor cells in vivo.
      The intravenous injection of IONP-PLL carrying NM23-H1-GFP plasmid DNA
      significantly extended the survival time of an experimental pulmonary metastasis
      mouse model. In the IONP-PLL/NM23-H1-GFP-treated group, metastasis was clearly
      suppressed compared with the group treated with free NM23-H1-GFP plasmid.
      Furthermore, this gene therapy combined with cyclophosphamide treatment resulted
      in longer survival times and greater suppression of metastasis growth. In
      conclusion, treatment with IONP-PLL nanoparticles incorporating the NM23-H1gene
      is an efficient gene therapy method, and it is even more effective in combination
      with chemotherapy. This approach appears to be a promising strategy for treatment
      of metastatic tumors.

PMID- 19096444
TI  - Transgene expression of alpha tumor necrosis factor with mutations D142N and
      A144R under control of human telomerase reverse transcriptase promoter eradicates
      well-established tumors and induces long-term antitumor immunity.
AB  - Recombinant adenoviral vectors (AdVTNF-alpha) expressing alpha tumor necrosis
      factor (TNF-alpha) under control of cytomegalovirus (CMV) promoter have been used
      in cancer gene therapy. To reduce its cytotoxicity, we constructed a recombinant
      AdV(TERT)mTNF-alpha expressing a mutant TNF-alpha (mTNF-alpha) with mutations at
      D142N and A144R under control of human telomerase reverse transcriptase (hTERT)
      promoter for treatment of well-established ovalbumin (OVA)-expressing murine B16
      melanoma (BL6-10(OVA)) (6 mm in diameter). We demonstrated that the mTNF-alpha
      with mutations at D142N and A144R has less in vitro cytotoxicity, but maintains
      its functional effect in the stimulation of T-cell proliferation. The in vitro
      and in vivo transgene expressions under control of hTERT promoter are highly
      restricted in tumor cells compared with those under the control of the CMV
      promoter. AdV(TERT)mTNF-alpha gene therapy by intratumoral injection of
      AdV(TERT)mTNF-alpha vector (2 x 10(9) PFU) expressing the mutant mTNF-alpha under
      control of hTERT promoter reduces its in vivo toxicity, eradicates well
      established BL6-10(OVA) tumors in 4/10 tumor-bearing mice, and induces OVA
      specific CD8(+) T-cell-mediated long-term antitumor immunity. Therefore,
      AdV(TERT)mTNF-alpha gene therapy may be very useful in the immunotherapy of
      cancer.

PMID- 19096445
TI  - Expression of HBX, an oncoprotein of hepatitis B virus, blocks reoviral oncolysis
      of hepatocellular carcinoma cells.
AB  - Although reovirus has been used in tests as a potential cancer therapeutic agent
      against a variety of cancer cells, its application to hepatocellular carcinoma
      cells, in which the hepatitis B virus (HBV) X (HBX) protein of HBV plays a
      primary role, has not yet been explored. Here, we describe experiments in which
      we use reovirus to treat Chang liver carcinoma cells expressing either a vector
      only (Chang-vec) or a vector encoding HBX protein (Chang-HBX). Although Chang-vec
      cells readily support reoviral proliferation and undergo apoptosis, Chang-HBX
      cells are highly resistant to reoviral infection and virus-induced apoptosis,
      even though HBX protein induces activation of Ras and inactivation of PKR, which
      are normally thought to enhance reoviral oncolysis. The resistance of Chang-HBX
      cells to reovirus may instead be explained by HBX-induced downregulation of death
      receptor 5 and activation of Stat1. Phosphorylated Stat1 activates interferon
      (IFN)-stimulated regulatory element (ISRE)- and IFN-gamma-activated sequence
      (GAS)-mediated transcription, leading to the production of IFN-beta, whereas the
      reduced expression of Stat1 with its siRNA results in a decrease in IFN-beta
      production, by which Chang-HBX cells eventually succumb to reovirus infection.
      This result further indicates that HBX induces the establishment of an antiviral
      state through Stat1 activation. Thus, it appears that active Ras does not
      override the antiviral effect mediated by the activation of Stat1. Accordingly,
      we report that HBX, an oncoprotein of HBV, can prevent reoviral oncolysis of
      hepatocellular carcinoma. This suggests there may be limits to the practical
      application of reovirus in the treatment of human cancers already expressing
      other oncoviral proteins.

PMID- 19096446
TI  - Retrovirally transduced murine T lymphocytes expressing FasL mediate effective
      killing of prostate cancer cells.
AB  - Adoptively transferred T cells possess anticancer activities partially mediated
      by T-cell FasL engagement of Fas tumor targets. However, antigen-induced T-cell
      activation and clonal expansion, which stimulates FasL activity, is often
      inefficient in tumors. As a gene therapy approach to overcome this obstacle, we
      have created oncoretroviral vectors to overexpress FasL or non-cleavable FasL
      (ncFasL) on murine T cells of a diverse T-cell receptor repertoire. Expression of
      c-FLIP was also engineered to prevent apoptosis of transduced cells. Retroviral
      transduction of murine T lymphocytes has historically been problematic, and we
      describe optimized T-cell transduction protocols involving CD3/CD28 co
      stimulation of T cells, transduction on ice using concentrated oncoretrovirus,
      and culture with IL-15. Genetically modified T cells home to established prostate
      cancer tumors in vivo. Co-stimulated T cells expressing FasL, ncFasL and ncFasL/c
      FLIP each mediated cytotoxicity in vitro against RM-1 and LNCaP prostate cancer
      cells. To evaluate the compatibility of this approach with current prostate
      cancer therapies, we exposed RM-1, LNCaP, and TRAMP-C1 cells to radiation,
      mitoxantrone, or docetaxel. Fas and H-2(b) expression were upregulated by these
      methods. We have developed a novel FasL-based immuno-gene therapy for prostate
      cancer that warrants further investigation given the apparent constitutive and
      inducible Fas pathway expression in this malignancy.

PMID- 19096447
TI  - Adoptive immunotherapy using human peripheral blood lymphocytes transferred with
      RNA encoding Her-2/neu-specific chimeric immune receptor in ovarian cancer
      xenograft model.
AB  - The current gene transfer technology for single chain (scFv)-based chimeric
      immune receptor (CIR) has relied on retrovirus and lentivirus vectors which
      require a long time to obtain sufficient number of transduced cells and stably
      incorporate into genome. To ameliorate these limitations, we applied RNA
      electroporation to human peripheral blood lymphocytes (PBLs) activated with anti
      CD3 antibody and interleukin-2 (IL-2) for 3 days and assessed that PBL
      transiently expressing anti-Her-2/neu CIR (CIR-PBL) containing signaling portion
      of CD28 and CD3zeta could elicit strong cytotoxicity in vitro and antitumor
      responses in vivo. The CIR-PBL expressed high level of CIR in CD4+, CD8+ and
      CD56+ cells. Her-2/neu-specific stimulation induced secretion of type-I cytokines
      including interferon-gamma (IFN-gamma), IL-8 and granulocyte-macrophage colony
      stimulating factor, and IFN-gamma secretion was mainly mediated by CD8+ T cells.
      CIR-PBL specifically killed SKOV3 cell line expressing Her-2/neu. Adoptive
      transfer of CIR-PBL in SKOV3 xenograft model led to significant inhibition of
      tumor growth compared with transfer of mock-transduced PBL and showed higher
      inhibition than those with Herceptin, humanized monoclonal antibody specific for
      Her-2/neu. These results provided evidence that electroporation of CIR RNA to
      human PBLs could be used for rapid generation and high number of therapeutic
      antigen-specific T cells for adoptive immunotherapy.

PMID- 19096449
TI  - Is there a role for chromaffin progenitor cells in neurodegenerative diseases?

PMID- 19096450
TI  - The neural correlates of moral decision-making in psychopathy.

PMID- 19096451
TI  - Multiple rare SAPAP3 missense variants in trichotillomania and OCD.

PMID- 19096452
TI  - Heat-shock-induced oxidative stress and antioxidant response in Aspergillus niger
      26.
AB  - To extend the knowledge about the relationship between heat shock and oxidative
      stress in lower eukaryotes, the filamentous fungus Aspergillus niger 26 was
      chosen as a model system. Here, the response of A. niger cells to heat shock is
      reported. The temperature treatment significantly increased the levels of
      reactive oxygen species, superoxide anions (O2), and hydrogen peroxide and the
      rate of cyanide-resistant respiration as a marker of oxidative stress. Enhanced
      reactive oxygen species generation coincided with an increase in the content of
      oxidative damaged protein and in the accumulation of the storage carbohydrates
      trehalose and glycogen. Thermal survival of the A. niger cells corresponded to a
      significant increase in the levels of the antioxidant enzymes superoxide
      dismutase and catalase for all variants. These observations suggest that heat and
      oxidative stress have a common cellular effect.

PMID- 19096453
TI  - Heterogeneity in enterohemorrhagic Escherichia coli O157:H7 fecal shedding in
      cattle is related to Escherichia coli O157:H7 colonization of the small and large
      intestine.
AB  - In the last decade, Escherichia coli O157:H7 have emerged as important pathogens
      of the gastrointestinal tract of humans. Healthy cattle have been identified as
      the primary reservoir, however, the factors affecting heterogeneous E. coli
      O157:H7 fecal shedding are not fully understood. The aim of this study was to
      investigate the contribution of E. coli O157:H7 colonization of small and large
      intestinal sites to the heterogeneity of fecal shedding in cattle. There was a
      dose-dependant E. coli O157:H7 E318N colonization of duodenum, jejunum, ileum,
      cecum, ascending colon, spiral colon, descending colon, and the rectoanal
      junction in vitro with no difference in E. coli O157:H7 colonization of the
      rectoanal junction and other intestinal sites. There were 10-100 times greater E.
      coli O157:H7 colonization of intestinal sites from persistent shedding cattle
      compared with non persistent shedding cattle. Novel pathologies were associated
      with E. coli O157:H7 colonization sites in the small and large intestine. The
      first pathology, focal petechiae, was present throughout the intestinal tract of
      cattle that ceased shedding E. coli O157:H7 for 5-12 weeks or in the jejunum,
      ileum, cecum, and ascending colon of cattle shedding E. coli O157:H7 for 4-5
      months. The second pathology, mucosal hemorrhages, was present in the same sites
      as the focal petechiae in cattle shedding for 5 months and these hemorrhages were
      in the final stages of repair. Several features of these hemorrhages support this
      conclusion including the brown appearance, low amount of classic E. coli O157:H7
      induced A/E lesions, flattened epithelium, and blunted villi. Although mucosal
      hemorrhages were present in the jejunum, ileum, cecum, and ascending colon in
      cattle shedding for 4 months, many other pathologies were also present that were
      indicative of hemorrhagic enteritis as evidenced by the blood red appearance of
      hemorrhages, severe edema, and dark red erythema. Escherichia coli O157:H7 were
      associated with both pathologies suggesting it is the causative agent. The
      current study supports a relationship between the amount of E. coli O157:H7
      colonization in intestinal sites and heterogeneous fecal shedding by cattle.

PMID- 19096454
TI  - Molecular bacterial diversity and distribution in waste from a steel plant.
AB  - We characterized the bacterial diversity of newly produced steelmaking wastes
      (NPSW) and steelmaking wastes deposited (SWD) in a restricted land area,
      generated by the siderurgic industry, using the 16S rDNA clone library approach.
      A total of 212 partial-length sequences were analyzed, revealing 123 distinct
      operational taxonomic units (OTUs) determined by the DOTUR program to 97%
      sequence similarity. Phylogenetic analysis of bacterial 16S rDNA sequences from
      the NPSW and SWD libraries demonstrated that Gammaproteobacteria,
      Betaproteobacteria, Alphaproteobacteria, Actinobacteria, Planctomycetes,
      Firmicutes, and Bacteroidetes were represented in both libraries.
      Deltaproteobacteria, Acidobacteria, Chloroflexi, Deinococcus-thermus,
      Gemmatimonadetes, and candidate divisions OP10 and OD1 were only present in the
      SWD library, and Nitrospira was only present in the NPSW library. The abundance
      of sequences affiliated with Gammaproteobacteria was high in both libraries. Six
      previously unclassified OTUs may represent novel taxa. Based on diversity indices
      (Simpson, Shannon-Weaver, Chao1, and ACE), the SWD library had a higher
      diversity. LIBSHUFF comparisons of the composition of the 2 libraries showed that
      they were significantly different. These results indicate that the bacterial
      communities in steelmaking wastes present high phylogenetic diversity and
      complexity. A possible association between the functional diversity and the
      bacterial communities' complexity requires further phenotypic investigation.

PMID- 19096455
TI  - Identification of human enteric pathogens in gull feces at Southwestern Lake
      Michigan bathing beaches.
AB  - Ring-billed (Larus delawarensis Ord, 1815) and herring (Larus argentatus
      Pontoppidan, 1763) gulls are predominant species of shorebirds in coastal areas.
      Gulls contribute to the fecal indicator burden in beach sands, which, once
      transported to bathing waters, may result in water quality failures. The
      importance of these contamination sources must not be overlooked when considering
      the impact of poor bathing water quality on human health. This study examined the
      occurrence of human enteric pathogens in gull populations at Racine, Wisconsin.
      For 12 weeks in 2004 and 2005, and 7 weeks in 2006, 724 gull fecal samples were
      examined for pathogen occurrence on traditional selective media (BBL CHROMagar
      Salmonella, Remel Campy-BAP, 7% horse blood agar) or through the use of novel
      isolation techniques (Campylobacter, EC FP5-funded CAMPYCHECK Project), and
      confirmed using polymerase chain reaction (PCR) for pathogens commonly harbored
      in gulls. An additional 226 gull fecal samples, collected in the same 12-week
      period in 2004, from a beach in Milwaukee, Wisconsin, were evaluated with
      standard microbiological methods and PCR. Five isolates of Salmonella (0.7%), 162
      (22.7%) isolates of Campylobacter, 3 isolates of Aeromonas hydrophila group 2
      (0.4%), and 28 isolates of Plesiomonas shigelloides (3.9%) were noted from the
      Racine beach. No occurrences of Salmonella and 3 isolates of Campylobacter (0.4%)
      were found at the Milwaukee beach. A subset of the 2004 samples was also examined
      for Giardia and Cryptosporidium and was found to be negative. Information as to
      the occurrence of human pathogens in beach ecosystems is essential to design
      further studies assessing human health risk and to determine the parameters
      influencing the fate and transport of pathogens in the nearshore environment.

PMID- 19096456
TI  - Sinusoidal magnetic field stimulates magnetosome formation and affects mamA,
      mms13, mms6, and magA expression in Magnetospirillum magneticum AMB-1.
AB  - Magnetic particles are currently one of the most important materials in the
      industrial sector, where they have been widely used for biotechnological and
      biomedical applications. To investigate the effects of the imposed magnetic field
      on biomineralization in Magnetospirillum magneticum AMB-1 and to suggest a new
      approach that enhances formation of magnetosomes, cultures inoculated with either
      magnetic or nonmagnetic precultures were incubated under a sinusoidal magnetic
      field or geomagnetic field. The results showed that the sinusoidal magnetic field
      up-regulated mms6 expression in the cultures inoculated with magnetic cells, and
      magA, mms6, and mamA expression in the cultures inoculated with nonmagnetic
      cells. The applied sinusoidal magnetic field could block cell division, which
      could contribute to a decrease in the OD600 values and an increase in the
      coefficient of magnetism values of the cultures, which could mean that the
      percentage of mature magnetosome-containing bacteria was increased. The linearity
      of magnetosome chains was affected, but the number of magnetic particles in cells
      was increased when a sinusoidal magnetic field was applied to the cultures. The
      results imply that the variable intensity and orientation of the sinusoidal
      magnetic field resulted in magnetic pole conversion in the newly forming magnetic
      particles, which could affect the formation of magnetic crystals and the
      arrangement of the adjacent magnetosome.

PMID- 19096457
TI  - Effects of xanthotoxin treatment on trichothecene production in Fusarium
      sporotrichioides.
AB  - There are 4 P450 oxygenases involved in the biosynthesis of T-2 toxin in Fusarium
      sporotrichioides. Exactly how these enzymes react to antimicrobial plant defense
      compounds is unknown. Xanthotoxin (8-methoxypsoralen) is a phototoxic
      furanocoumarin that acts as a P450 oxygenase inhibitor. The current study shows
      that the addition of concentrations of 1.0 mmol/L or less of xanthotoxin to
      liquid cultures of F. sporotrichioides NRRL3299 can effectively block T-2 toxin
      production and cause an increase in accumulation of trichodiene, the hydrocarbon
      precursor of trichothecenes. The addition of xanthotoxin to liquid cultures of a
      trichodiene-accumulating F. sporotrichioides Tri4- mutant caused a 3- to 10-fold
      increase in trichodiene accumulation, suggesting that xanthotoxin not only blocks
      trichothecene oxygenation reactions, but may in some way also promote the
      synthesis of trichodiene. Feeding studies showed that 2 of the 4 P450 oxygenases,
      TRI4 and TRI1, were more sensitive to xanthotoxin, while oxygenases TRI11 and
      TRI13 were unaffected. Quantitative reverse-transcriptase PCR indicated that
      several of the genes in the toxin biosynthetic pathway were upregulated by
      xanthotoxin, with Tri4 showing the highest increase in expression. These results
      indicate that while xanthotoxin inhibits specific P450 oxygenase activity, it
      also has an effect on gene expression.

PMID- 19096458
TI  - Innate immunity prevents tissue invasion by Entamoeba histolytica.
AB  - Although innate and adaptive immunity both play a role in amoebiasis, the
      mechanisms involved in the elimination of Entamoeba histolytica are poorly
      understood. To provide more information about the innate immune mechanisms that
      may confer protection against invasive amoebiasis, we administered inflammatory
      substances (bacillus Calmette-Guerin, lipopolysaccharide, complete Freund's
      adjuvant, or mineral oil) into the peritoneum of hamsters. The animals were then
      challenged with pathogenic trophozoites of E. histolytica and, after 7 days, the
      protective host response was analysed. We found that the nonspecific inflammatory
      response induced in the peritoneum was sufficient to prevent liver invasion by E.
      histolytica. In vitro experiments showed that the killing of trophozoites was
      mediated by peritoneal macrophages and a protein of 68 kDa with peroxidase
      activity.

PMID- 19096459
TI  - Bacterial chemotaxis differences in Escherichia coli isolated from different
      hosts.
AB  - The mechanisms mediating the association between Escherichia coli and specific
      hosts are unknown. This study investigates the hypothesis that the host-specific
      associations of E. coli strains are mediated in part by differences in
      chemotaxis. To test this hypothesis, chemotactic responses of E. coli strains
      isolated from different host groups (carnivores, herbivores, and omnivores) were
      tested with various attractants. In low-density agar chemotaxis assays, the
      average motility of E. coli in response to aspartate, serine, and ribose among
      the different groups was not significantly different; however, strains from
      carnivores responded significantly more to aspartate, relative to their responses
      to serine, in comparison with strains from herbivores, which responded equally or
      better to serine than to aspartate. The relatively greater chemotactic response
      of strains from carnivores to aspartate than to serine was confirmed in a subset
      of strains by capillary chemotaxis assay. Differences in responses to serine and
      aspartate were not due to growth differences, as determined by comparison of 24 h
      growth curves with glycerol, aspartate, and serine carbon sources. The
      differences in chemotactic behavior of E. coli strains isolated from herbivores
      and carnivores support the hypothesis that host-specific associations of E. coli
      strains are mediated in part by differences in chemotactic behavior.

PMID- 19096460
TI  - Spatial distribution of bacterial communities in sediment of a eutrophic lake
      revealed by denaturing gradient gel electrophoresis and multivariate analysis.
AB  - Bacterial community structure and the effects of several environmental factors on
      the microbial community distribution were investigated in the sediment of the
      eutrophic Lake Xuanwu. Profiles of bacterial communities were generated using
      denaturing gradient gel electrophoresis (DGGE), and the results were interpreted
      with multivariate statistical analysis. Five major variables in sediment were
      examined in a principal component analysis, which indicates notable differences
      of physicochemical parameters among different sites of the lake. To assess
      changes in the genetic diversity of bacterial communities of different sampling
      sites, DGGE band patterns were analyzed by multidimensional scaling analysis,
      which indicated that sampling sites having similar environmental characteristics
      also have the similar microbial communities. Canonical correspondence analysis
      demonstrated that pH and redox potential had significant effects on the bacterial
      community composition in the sediments. Analysis of DNA sequences revealed that
      the dominant bacterial groups in Lake Xuanwu belonged to Proteobacteria,
      Actinobacteria, Verrucomicrobia, and Nitrospirae, which are commonly isolated
      from freshwater ecosystems.

PMID- 19096461
TI  - Isolation and characterization of silicate mineral-solubilizing Bacillus
      globisporus Q12 from the surfaces of weathered feldspar.
AB  - A silicate mineral-solubilizing bacterial strain Q12 was isolated from the
      surfaces of weathered feldspar and identified as Bacillus globisporus Q12 based
      on the 16S rDNA gene sequence analysis. Three silicate minerals (feldspar,
      muscovite, and biotite) were used to investigate potassium and silicon
      mobilization by strain Q12. In liquid cultures, the strain showed better growth
      on the biotite than on feldspar and muscovite. The biotite was the best potassium
      source for growth of the strain. Solubilization of potassium and silicon from the
      silicate minerals by the strain resulted mostly from the action of organic acids.
      Gluconic acid seemed to be the most active agent for the solubilization of the 3
      silicate minerals. Gluconic and acetic acids were likely involved in the
      solubilization of feldspar. The strain could be acid or alkali and salt tolerant
      and temperature resistant.

PMID- 19096462
TI  - [The potential of death].

PMID- 19096463
TI  - [Home childbirth--safe enough for the mother and the child?].

PMID- 19096464
TI  - [Utilization of diagnostic tools and health care services for obstructive lung
      disease].
AB  - BACKGROUND: Chronic obstructive pulmonary disease (COPD) has been under-diagnosed
      and the patients are commonly misdiagnosed as having asthma. Due to the lack of
      recent data on Norwegian COPD diagnoses, we wished to assess the development of
      diagnosing and treating COPD and asthma in Norway. MATERIAL AND METHODS: We
      identified patients with an ICPC-diagnosis of COPD and/or asthma at eight primary
      health care centres in Norway, 1995 - 2004. Data on prescription of medical
      drugs, spirometry testing, visits to casualty/outpatient clinics, and
      hospitalization were retrieved from electronic sources. RESULTS: The diagnosis
      COPD was used increasingly over the study period, while the the use of the asthma
      diagnosis declined in the oldest age-groups. The proportion of COPD patients
      tested with spirometry increased from 24 % (68/288) in 1995 - 96, to 41 % in 2003
      - 04. 16 % of COPD patients were in contact with out-of-hours services, 19 % had
      an outpatient consultation, and 24 % were hospitalized the same calendar year as
      the diagnosis was given in general practice. Corresponding numbers for asthma
      patients were substantially lower. INTERPRETATION: The increased use of the COPD
      diagnosis indicates improved diagnostic routines, probably because of increased
      use of spirometry in primary care. Early and correct diagnosis contributes to
      more optimal use of medication and improved follow/up.

PMID- 19096465
TI  - [Outcomes after planned home births].
AB  - BACKGROUND: About 150 planned home births take place in Norway annually.
      Professionals have different opinions on whether such births are safe or not. The
      aim of the present study was to perform a systematic literature review on
      maternal and neonatal outcomes after planned home births. MATERIAL AND METHODS: A
      review was performed of literature retrieved from searches in MEDLINE, PubMed,
      Embase, Cinahl and The Cochrane Library and relevant references found in the
      articles. The searches were limited to studies published in 1985 and later.
      RESULTS: 10 studies with data from 30 204 women who had planned and were selected
      to home birth at the onset of labour were included. Three of the studies had
      control groups including women with planned hospital births. All included studies
      were assessed to be of medium quality. Between 9.9 and 23.1 % of women and
      infants were transferred to hospital during labour or after birth. There were few
      caesarean sections, other interventions or complications in the studies assessed;
      the total perinatal mortality rate was 2.9/1000 and the intrapartum mortality
      rate 0.8/1000. INTERPRETATION: There is no sound basis for discouraging low-risk
      women from planning a home birth. Results from the included studies do not
      directly apply to Norwegian conditions. Outcomes and transfers after planned home
      births should be systematically registered.

PMID- 19096466
TI  - [Should platelet inhibitors be discontinued before gastrointestinal endoscopy?].
AB  - BACKGROUND: . In Norway, different attitudes prevail to discontinuation of
      antiplatelet agents, such as ASA, NSAID, ADP-receptor inhibitors (clopidogrel and
      ticlopidine) phosphodiestase inhibitors (dipyridamole) and glycoprotein IIb/IIIa
      receptor inhibitors (abciximab and eptifibatide), before endoscopic procedures.
      The Norwegian Association of Gastroenterology have appointed a group, consisting
      of a medical and a surgical gastroenterologist, a haematologist, a cardiologist
      and a pharmacologist, to review literature concerning the issue in order to give
      a recommendation. MATERIAL AND METHODS: Literature retrieved from a non
      systematic search of Pubmed was critically reviewed by the study group. RESULTS:
      No randomised controlled studies were found to have addressed the problem. Two
      prospective and three retrospective studies have compared the frequency of
      bleeding complications for patients using or not using ASA/NSAID during
      endoscopic papillotomy or polypectomy. The studies showed either no differences
      in bleeding complications, or only an increase in mild, self-limiting haemorrhage
      for those using ASA/NSAID. INTERPRETATION: The group recommends that all
      gastroenterological procedures may be performed on patients taking ASA/NSAID
      provided there are no pre-existing bleeding disorders. As no clinical data are
      available for other antiplatelet agents, the group recommends to stop the
      treatment for 7 days before the procedure, but this will have to be balanced
      against the risk of thrombosis associated with the discontinuation.

PMID- 19096467
TI  - [Clerkship in general practice--organized for learning?].
AB  - BACKGROUND: Clerkship in general practice has been considered removed from the
      fifth year at the University of Oslo for economical reasons. During the autumn
      2007, we evaluated the clerkship after the implementation of a new feedback tool,
      StudPEP. This study presents how the clerkship was organized for learning based
      on pedagogical advice for effective learning. MATERIAL AND METHODS: 79 of 81
      students completed a questionnaire regarding the clerkship. After five
      independent tutor-observed consultations, the students recorded their patients'
      diagnosis, age and gender, in a total of 363 consultations. RESULTS: The students
      received eight patients per day on average during their last week of clerkship.
      On average, they had their own office during 64 % of their clerkship, but 19 %
      had their own office in less than a third of the time. The tutor observed 42 % of
      the students during more than six consultations in addition to the five
      compulsory ones, but 23 % of the students were only observed during the five
      compulsory sessions. The students were generally content with the feedback from
      their tutor, but 20 % gave critical answers. The students recorded 167 different
      diagnoses from all the chapters in the International Classification of Primary
      Care. INTERPRETATION: The clerkship is well organized for learning medicine in
      general practice. There is a potential for quality improvement and this article
      presents suggestions from educational literature.

PMID- 19096468
TI  - [Bacterial resistance against antibiotics].
AB  - BACKGROUND: Antibiotic resistance has progressed over many decades and is
      increasingly problematic. This paper gives a short summary of antibiotic
      resistance and its biology. MATERIAL AND METHODS: The authors have worked in this
      field for many years. References to major overviews and important work are given,
      but no systematic literature search has been done. RESULTS: Development of
      resistance is driven by positive selection of resistant clones of bacteria. There
      are multiple, often interlinked molecular mechanisms behind this resistance, and
      they all lead to a less effective interaction between antibiotics and their
      target. INTERPRETATION: Many observations of antibiotic resistance phenomena and
      their development over the last decades indicate that the problem is substantial,
      persisting and increasing. It will probably have an important impact on many
      medical disciplines in the future. Work to counteract this development is needed
      in every medical field in order to halt and hopefully counteract resistance
      development as strongly as we can.

PMID- 19096469
TI  - [Antimicrobial resistance after antibiotic use in animals--impact on human
      health].
AB  - BACKGROUND: This review describes the use of antibiotics and the occurrence of
      antimicrobial resistance in animal husbandry, with emphasis on the current
      situation in Norway. The clinically most important resistance problems in human
      medicine that are associated with antimicrobial resistance in animals, are
      discussed in a global perspective. MATERIAL AND METHODS: This review is based on
      a Pubmed search with the terms "animal" and "antimicrobial resistance", as well
      as the authors' own research experience. RESULTS: Antibiotic use in animals is
      the main cause for selection and dissemination of antimicrobial resistance in
      animals. The prevalence of antimicrobial resistance in animal husbandry in Norway
      is lower than that in many non-Nordic countries, and is associated with less use
      of therapeutic antibiotics. Antimicrobial resistance may spread from animals to
      humans by transfer of resistant bacteria from animals to humans and resistance
      genes from animal bacteria to human pathogens. INTERPRETATION: It is adamant to
      have efficient prevention measures and rational use of antibiotics in animals to
      delay development of antibiotic resistant bacteria. Although good examples exist
      of how resistance in animal bacteria can create problems for human health, it is
      well documented that the human use of therapeutic antibiotics and lack of
      efficient infection control measures have the most profound influence on the
      occurrence of antibiotic resistance in humans.

PMID- 19096470
TI  - [Antimicrobial resistance in developing countries].
AB  - BACKGROUND: While bacterial infections are one of the most important causes of
      disease and death in developing countries, the prevalence and consequences of
      antimicrobial resistance are not well known. MATERIAL AND METHODS: This is a
      review article based on literature retrieved from a non-systematic review and own
      experience from research on the topic. RESULTS: Research on antimicrobial
      resistance is increasing in developing countries, but most of the data are
      obtained from referral hospitals in capitals and major cities. Multiresistant
      Gram-negative bacteria, including ESBL-(extended-spectrum beta-lactamase)
      producing bacteria have been documented in several countries and are associated
      with increased lethality. The most serious resistance problems in developing
      countries are associated with Gram-negative bacteria and tuberculosis and may
      result in increased risk of death. INTERPRETATION: Developing countries have a
      much higher overall burden of infectious diseases than the rich western countries
      and also poor access to newer antibiotics, which can be lifesaving when treating
      infections caused by resistant bacteria. To combat overuse and misuse of
      antibiotics, the diagnosis of infectious diseases must be strengthened and
      antimicrobial resistance must be emphasized in education of health professionals
      and the general public. There is a need for improved surveillance of
      antimicrobial resistance and strengthened quality control of antimicrobial drugs.
      In the long-term perspective, poverty reduction, improved living conditions and
      hygiene, safe water supplies and access to quality health care (including
      vaccination and HIV care), may contribute to prevent emerging antimicrobial
      resistance.

PMID- 19096471
TI  - [Antibiotic treatment of women with group B Steptococci during delivery?].
AB  - BACKGROUND: Transmission of group B Steptococci from mother to child during
      delivery may cause serious disease in some children, but this can be prevented by
      use of antibiotic treatment during delivery. We have estimated how antibiotic
      treatment of all pregnant carriers of group B streptococcus during delivery would
      affect the total antibiotic use in Norway. MATERIAL AND METHODS: We estimated the
      use of penicillin G for treatment of 10 %, 20 % and 30 % of streptococcus
      carriers among those delivering. The Medical Birth Registry was used to obtain
      number of births and the Norwegian Drug Wholesalers Database to obtain total use
      of the various substances. RESULTS: If 30 % of delivering women were carriers of
      group B streptococcus and treated with penicillin G, the treatment would equal
      2.8 % of today's total use of penicillin G and 0.09 % of the total use of the
      whole group of beta-lactam antibacterial agents, penicillins. INTERPRETATION:
      Prophylactic antibiotic treatment of pregnant carriers of group B streptococcus
      during delivery would not lead to a substantial change in the current antibiotic
      use. The possibility of increasing antibiotic resistance should not be a main
      argument against using antibiotics in prevention of group B streptococcus
      infection in newborns.

PMID- 19096472
TI  - [What is needed to supervise the nation's health?].

PMID- 19096473
TI  - [Blood specimen collection should be performed by qualifies personnel].

PMID- 19096474
TI  - [Writing on the wall].

PMID- 19096475
TI  - [To be wrong].

PMID- 19096476
TI  - [Problem solving or problem wasting?].

PMID- 19096477
TI  - [Discovering a masterpiece--the Russian physician and author Leonid Tsypkin (1926
      82)].
AB  - The paper presents a literary work unknown to most readers. The Russian author
      Leonid Tsypkin (1926 - 82) is among those who were discovered and even declared
      literary geniuses after their dead. He never saw a line of his own fiction
      published. Tsypkin studied medicine in Minsk in Belarus and later practiced as a
      pathologist in Moscow where he obtained two PhDs and authored numerous scientific
      publications. In his novel "Summer in Baden-Baden", the Jew Tsypkin declares his
      love to the anti-Semitic author Fjodor Dostojevskij. Tsypkins' own life became
      more and more complicated due to anti-Semitism in the Soviet Union.

PMID- 19096479
TI  - [MedHum 2007--how did it go?].

PMID- 19096482
TI  - [When the editor makes an error].

PMID- 19096483
TI  - [The selected contagions].

PMID- 19096484
TI  - [The metabolic syndrome among obese patients].
AB  - BACKGROUND: The metabolic syndrome is a widely prevalent constellation of risk
      factors for cardiovascular disease. We examined the prevalence and determinants
      of the metabolic syndrome in overweight/obese patients requesting treatment.
      MATERIAL AND METHODS: We conducted a retrospective journal search for patients
      with a diagnosis of obesity that were examined at the Department of Preventive
      Cardiology, Ullevaal University Hospital between 1999 - 2002. The patients were
      self-referred (14 %) or referred from primary (55 %) or secondary care (27 %). We
      compared the definition of the metabolic syndrome modified by the National
      Cholesterol Education Program with that used by the International Diabetes
      Federation (IDF). RESULTS: Of 162 women and 116 men (mean body mass index of 39
      kg/m 2 ), 71 % (95 % CI 66 % - 77 %) met both sets of criteria. Only 16 women and
      two men had no other components of the metabolic syndrome than an elevated waist
      circumference. Patients with the metabolic syndrome were older (47 years versus
      43 years; p = 0.005) and had more prevalent cardiovascular disease (16 % versus 6
      %; p = 0.05) than those without the syndrome. Men had a higher prevalence of the
      metabolic syndrome than women (81 % versus 66 %, p = 0.007) and higher systolic
      blood pressure and triglyceride levels. INTERPRETATION: We conclude that both
      definitions identify nearly the same populations among obese patients. Men should
      be encouraged more strongly to enrol in obesity treatment programs because of
      their metabolic risk profile.

PMID- 19096485
TI  - [Do physicians' gender and workload affect patients?].
AB  - BACKGROUND: The article discusses the effect of general practitioners' gender and
      workload on patients' experience with consultation time, waiting hours, use of
      out-of-hours services and planned health visits. MATERIAL AND METHODS: Data were
      retrieved from the 2003 version of Statistics Norway's household panel study
      (5000 persons) and the National Insurance administration's register of regular
      general practitioners. RESULTS: Health condition was the most important factor
      related to patient experiences. A high workload was neither associated with more
      frequent use of out-of-hours services nor satisfaction with time spent in
      consultation. These results apply to physicians of both genders. Patients who
      used a female physician with a large workload had to wait longer for an
      appointment and more often reported dissatisfaction with the waiting time; this
      was not the case for male physicians. However, male physicians with a low
      workload had shorter waiting times. INTERPRETATION: Patients who use
      practitioners with a high workload may have chosen their doctor more deliberately
      than others, which may be an explanation for few negative outcomes for physicians
      with a high workload. It is unlikely that these physicians would be as popular if
      the patients had fewer appointments, shorter consultations or more often had to
      use the out-of-hours services. Longer waiting time for appointments with female
      doctors may be related to more part time work, and the fact that female
      physicians more often are engaged in group practices.

PMID- 19096486
TI  - [Cancer risk in coeliac disease].
AB  - BACKGROUND: Coeliac disease is a common disease which seems to be considered less
      harmful now than previously. An association between coeliac disease and some
      types of cancer is well known. It is thus important to evaluate the seriousness
      of the condition and give patients advice and proper follow-up. MATERIAL AND
      METHODS: The article is based upon literature retrieved through a non-systematic
      search of PubMed. There are no Norwegian, but several European studies on the
      topic. Study design and patient selection varies. RESULTS: Most studies show
      increased cancer risk and mortality, especially for B-and T-cell lymphoma also
      outside the gut. The risk of breast and lung cancer is decreased. The studies
      show that the risk of mortality and cancer development is most pronounced the
      first three years after coeliac disease is diagnosed. The mortality of patients
      with coeliac disease during this period is nearly doubled in relation to a
      control population. There does not seem to be an increased cancer risk when the
      disease is diagnosed during childhood. Adherance to a gluten-free diet is at
      least partly protective. INTERPRETATION: Coeliac disease causes a certain
      increased risk of cancer and early death. It is not an innocent condition. This
      strengthens the arguments for coeliac patients to adhere to a gluten free diet.

PMID- 19096487
TI  - [Patient Activation Measure].
AB  - BACKGROUND: Patient education is a mandatory activity for Norwegian hospitals,
      but its effects have not been possible to assess properly due to lack of suitable
      instruments in Norwegian. This article describes the work undertaken to find a
      suitable questionnaire, translate it to Norwegian and validate it. MATERIAL AND
      METHODS: The heads of centres for patient education in the hospitals in Central
      Norway were presented with 15 different questionnaires measuring various areas -
      for example quality of life and coping. They were then asked to pick out
      the/those instruments which in their opinion best captured the aim of patient
      education. The unanimously chosen questionnaire was translated from English to
      Norwegian and back and was then validated in two samples of patients. RESULTS:
      The American "Patient Activation Measure (PAM)" was chosen because it focused on
      the patients' own efforts, was viewed as respectful and patient-oriented and
      emphasised self- management skills, knowledge and ability to choose. The
      correlation between PAM score and a question about ability to take care of own
      health was good (r = 0.477, p = 0.018) and the test-retest showed good
      reliability. INTERPRETATION: The Norwegian version of PAM is suitable as a
      measure of knowledge, skills, and ability to cope with own health and use of
      health services. The questionnaire is suitable for evaluation of interventions
      aimed at activating patients' ability to take care of their own health.

PMID- 19096488
TI  - [Antibiotic use in Norway].
AB  - BACKGROUND: Antibiotic use is a major cause of development and spread of
      resistant bacteria. Sensible antibiotic use should aim at decreasing total
      antibiotic use and replace broad-spectrum antibiotics with narrow-spectrum ones;
      pharmaceutical drug statistics are vital in this context. MATERIAL AND METHODS:
      Data were collected from the wholesaler-based drug statistics (for the period
      1974 - 2007) and from the Norwegian Prescription Database (2006). The ATC/DDD
      methodology is used in the drug statistics. Data are presented as number of users
      (prevalence), number of dispensed prescriptions, defined daily doses (DDD per 1
      000 inhabitants per day) and in Norwegian kroner. RESULTS AND INTERPRETATIONS:
      Longitudinal trends show a relatively stable and high use of narrow-spectrum
      antibiotics, even though broad-spectrum antibiotic use is slightly increasing.
      Antibiotic use varies largely by age and sex. The highest prevalences are seen
      among small children (0 - 5 years), women in their twenties and in people over 70
      years. Over 30 % of people in these groups receive at least one antibiotic per
      year. The therapy profile differs between the types of prescription issued.
      Neither the wholesaler statistics nor the Prescription Database contains
      information on diagnosis, making it difficult to monitor whether the Norwegian
      primary health service has a rational antibiotic therapy.

PMID- 19096489
TI  - [New guidelines for antibiotic use in primary health care].
AB  - BACKGROUND: In 2000, the first national guideline is on antibiotic use in general
      practice wee distributed to all general practitioners and medical students in
      Norway. Here we describe the development of new guidelines. MATERIAL AND METHODS:
      A working group of 30 people searched relevant databases for literature. We have
      especially used research from Norway and from general practice and nursing homes.
      RESULTS: The main recommendations of the 2000 guidelines are upheld. For upper
      respiratory tract infections there is now an even better evidence base to support
      strict indications for antibiotic treatment. INTERPRETATION: A good evidence base
      supports continuation of the Norwegian tradition of prudent antibiotic use in
      primary health care. In some areas there is insufficient research. After an
      initiative from the Directorate of Health, the Antibiotic Centre for Primary
      Medicine have developed the new guidelines as a part of the governmental strategy
      to combat antimicrobial resistance. Prudent antibiotic use is seen as an
      important measure. For this reason, the guidelines will also be printed in a
      booklet that will be sent to general practitioners, medical students and nursing
      homes.

PMID- 19096490
TI  - [Rational use of antibiotics in hospitals].
AB  - BACKGROUND: The Norwegian antibiotic policy emphasises use of narrow-spectrum
      antibiotics and has been regarded as successful. We have a low occurrence of
      antibiotic resistance, but hospital use of antibiotics in general, and broad
      spectrum antibiotics specifically, has increased substantially the last 10 years.
      We now see a trend towards increasing antibiotic resistance, which will
      inevitably lead to the same serious resistance problems in Norway as abroad.
      MATERIAL AND METHODS: We have assessed resistance profiles for the most common
      human pathogens in Norway in the light of literature retrieved through a non
      systematic search of PubMed and Norwegian literature on rational antibiotic use.
      The article emphasises pharmacodynamic and pharmacokinetic aspects, as well as
      ecological side effects of antibiotics and discusses rational treatment of the
      most common infections in Norwegian hospitals. RESULTS: Most research in this
      context is performed in settings with different antibiotic resistance patterns
      and attitudes towards antibiotic treatment than in Norway; few studies have
      focused on rational antibiotic use in Norwegian hospitals. We conclude that "old
      fashioned" narrow-spectrum antibiotics can still be used in Norwegian hospitals,
      as there is little resistance to these agents. INTERPRETATION: It is still
      possible to treat most infections in Norwegian hospitals with narrow-spectrum
      antibiotics. We encourage physicians to adhere to the Norwegian antibiotic
      therapy tradition.

PMID- 19096491
TI  - [Is otitis and tonsillitis handled in the same way within normal working hours
      and out-of-hours?].
AB  - BACKGROUND: Several factors influence physicians' prescribing of antibiotics. The
      purpose of this study is to see whether physicians use diagnostic testing and
      prescribe antibiotics differently for acute otitis media (AOM) and tonsillitis
      when they work within normal working hours and out-of-hours. MATERIAL AND
      METHODS: The study was a retrospective study of electronic patient records in a 6
      month period, from 1.09.1998 to 31.3.1999. All journal notes from the out-of
      hours services and the participating general practice clinics were examined. The
      following variables were recorded: diagnosis, patient age and gender, use of C
      reactive protein (CRP) and StrepA testing and treatment. RESULTS: In the
      diagnosis of AOM, CRP was used in 8 % of patients cared for out-of-hours and 6 %
      of those treated during normal working hours. There was no significant difference
      between the proportion of patients treated with antibiotics out-of-hours (74 %)
      and within normal working hours (73 %), but individual physicians differed
      significantly with respect to prescription of antibiotics and use of diagnostic
      tests. In the diagnosis of tonsillitis, either StrepA antigen test, CRP, or both
      tests were used in 65 % of patients cared for out-of-hours and in 50 % of those
      cared for during normal working hours. There was no significant difference in the
      proportion of patients treated with antibiotics out-of-hours (76 %) or during
      normal working hours (69 %). INTERPRETATION: Individual physicians use diagnostic
      testing and prescribe antibiotics in a similar way within and out-of-hours, but
      there were significant differences between individual physicians.

PMID- 19096492
TI  - [Fighting antibiotic resistance].
AB  - BACKGROUND: Due to the emergence and spread of antibiotic resistance, several
      infectious diseases are no longer treatable with standard drugs, and in many
      cases there are no adequate therapeutic options. Even though the situation in the
      Nordic countries is considerably better than in large parts of the world, we must
      also contribute to fight this development. In addition to continuing the prudent
      use of antibiotics, it is important to strengthen certain infection control
      strategies. WHO has stated that antibiotic resistance is a global health problem.
      MATERIAL AND METHODS: The article is based on personal experience from infection
      control and infectious diseases, and impressions from discussions in National and
      Nordic forums during the last years. We have also reviewed literature retrieved
      from non-systematic database searches. RESULTS AND INTERPRETATION: The
      introduction of pneumococcal vaccine in the Norwegian Childhood Vaccination
      Programme will probably contribute to both reducing the use of antibiotics, and
      preventing the spread of pneumococci that are resistant to antibiotics. Increased
      influenza vaccination uptake, standard barrier precautions (hand hygiene etc.)
      against infections in health care institutions, isolation and surveillance of
      resistant bacteria are among the most important infection control measures that
      should be strengthened if we are to succeed.

PMID- 19096493
TI  - [Climate and health].

PMID- 19096495
TI  - [Physicians' criticism].

PMID- 19096497
TI  - [Watering flowers in the neighbour's garden].

PMID- 19096499
TI  - Synthesis of 1,4-dihydro-benzo[d][1,3]oxazin-2-ones from phthalides via an
      aminolysis-Hofmann rearrangement protocol.
AB  - A simple two-step procedure for the conversion of readily available phthalides to
      the corresponding benzoxazinones was developed. Initial ring-opening aminolysis
      to form a primary 2-hydroxymethylbenzamide, followed by reaction with
      bis(trifluoroacetoxy)iodobenzene (BTI) conveniently provided a variety of 4
      substituted benzoxazinones.

PMID- 19096500
TI  - Disordered flanks prevent peptide aggregation.
AB  - Natively unstructured or disordered regions appear to be abundant in eukaryotic
      proteins. Many such regions have been found alongside small linear binding
      motifs. We report a Monte Carlo study that aims to elucidate the role of
      disordered regions adjacent to such binding motifs. The coarse-grained
      simulations show that small hydrophobic peptides without disordered flanks tend
      to aggregate under conditions where peptides embedded in unstructured peptide
      sequences are stable as monomers or as part of small micelle-like clusters.
      Surprisingly, the binding free energy of the motif is barely decreased by the
      presence of disordered flanking regions, although it is sensitive to the loss of
      entropy of the motif itself upon binding. This latter effect allows for
      reversible binding of the signalling motif to the substrate. The work provides
      insights into a mechanism that prevents the aggregation of signalling peptides,
      distinct from the general mechanism of protein folding, and provides a testable
      hypothesis to explain the abundance of disordered regions in proteins.

PMID- 19096501
TI  - Malleable machines in transcription regulation: the mediator complex.
AB  - The Mediator complex provides an interface between gene-specific regulatory
      proteins and the general transcription machinery including RNA polymerase II
      (RNAP II). The complex has a modular architecture (Head, Middle, and Tail) and
      cryoelectron microscopy analysis suggested that it undergoes dramatic
      conformational changes upon interactions with activators and RNAP II. These
      rearrangements have been proposed to play a role in the assembly of the
      preinitiation complex and also to contribute to the regulatory mechanism of
      Mediator. In analogy to many regulatory and transcriptional proteins, we reasoned
      that Mediator might also utilize intrinsically disordered regions (IDRs) to
      facilitate structural transitions and transmit transcriptional signals. Indeed, a
      high prevalence of IDRs was found in various subunits of Mediator from both
      Saccharomyces cerevisiae and Homo sapiens, especially in the Tail and the Middle
      modules. The level of disorder increases from yeast to man, although in both
      organisms it significantly exceeds that of multiprotein complexes of a similar
      size. IDRs can contribute to Mediator's function in three different ways: they
      can individually serve as target sites for multiple partners having distinctive
      structures; they can act as malleable linkers connecting globular domains that
      impart modular functionality on the complex; and they can also facilitate
      assembly and disassembly of complexes in response to regulatory signals. Short
      segments of IDRs, termed molecular recognition features (MoRFs) distinguished by
      a high protein-protein interaction propensity, were identified in 16 and 19
      subunits of the yeast and human Mediator, respectively. In Saccharomyces
      cerevisiae, the functional roles of 11 MoRFs have been experimentally verified,
      and those in the Med8/Med18/Med20 and Med7/Med21 complexes were structurally
      confirmed. Although the Saccharomyces cerevisiae and Homo sapiens Mediator
      sequences are only weakly conserved, the arrangements of the disordered regions
      and their embedded interaction sites are quite similar in the two organisms. All
      of these data suggest an integral role for intrinsic disorder in Mediator's
      function.

PMID- 19096502
TI  - Dependence of bacterial chemotaxis on gradient shape and adaptation rate.
AB  - Simulation of cellular behavior on multiple scales requires models that are
      sufficiently detailed to capture central intracellular processes but at the same
      time enable the simulation of entire cell populations in a computationally cheap
      way. In this paper we present RapidCell, a hybrid model of chemotactic
      Escherichia coli that combines the Monod-Wyman-Changeux signal processing by
      mixed chemoreceptor clusters, the adaptation dynamics described by ordinary
      differential equations, and a detailed model of cell tumbling. Our model
      dramatically reduces computational costs and allows the highly efficient
      simulation of E. coli chemotaxis. We use the model to investigate chemotaxis in
      different gradients, and suggest a new, constant-activity type of gradient to
      systematically study chemotactic behavior of virtual bacteria. Using the unique
      properties of this gradient, we show that optimal chemotaxis is observed in a
      narrow range of CheA kinase activity, where concentration of the response
      regulator CheY-P falls into the operating range of flagellar motors. Our
      simulations also confirm that the CheB phosphorylation feedback improves
      chemotactic efficiency by shifting the average CheY-P concentration to fit the
      motor operating range. Our results suggest that in liquid media the variability
      in adaptation times among cells may be evolutionary favorable to ensure
      coexistence of subpopulations that will be optimally tactic in different
      gradients. However, in a porous medium (agar) such variability appears to be less
      important, because agar structure poses mainly negative selection against
      subpopulations with low levels of adaptation enzymes. RapidCell is available from
      the authors upon request.

PMID- 19096503
TI  - Association rate constants of ras-effector interactions are evolutionarily
      conserved.
AB  - Evolutionary conservation of protein interaction properties has been shown to be
      a valuable indication for functional importance. Here we use homology interface
      modeling of 10 Ras-effector complexes by selecting ortholog proteins from 12
      organisms representing the major eukaryotic branches, except plants. We find that
      with increasing divergence time the sequence similarity decreases with respect to
      the human protein, but the affinities and association rate constants are
      conserved as predicted by the protein design algorithm, FoldX. In parallel we
      have done computer simulations on a minimal network based on Ras-effector
      interactions, and our results indicate that in the absence of negative feedback,
      changes in kinetics that result in similar binding constants have strong
      consequences on network behavior. This, together with the previous results,
      suggests an important biological role, not only for equilibrium binding constants
      but also for kinetics in signaling processes involving Ras-effector interactions.
      Our findings are important to take into consideration in system biology
      approaches and simulations of biological networks.

PMID- 19096504
TI  - A simple screen to identify promoters conferring high levels of phenotypic noise.
AB  - Genetically identical populations of unicellular organisms often show marked
      variation in some phenotypic traits. To investigate the molecular causes and
      possible biological functions of this phenotypic noise, it would be useful to
      have a method to identify genes whose expression varies stochastically on a
      certain time scale. Here, we developed such a method and used it for identifying
      genes with high levels of phenotypic noise in Salmonella enterica ssp. I serovar
      Typhimurium (S. Typhimurium). We created a genomic plasmid library fused to a
      green fluorescent protein (GFP) reporter and subjected replicate populations
      harboring this library to fluctuating selection for GFP expression using
      fluorescent-activated cell sorting (FACS). After seven rounds of fluctuating
      selection, the populations were strongly enriched for promoters that showed a
      high amount of noise in gene expression. Our results indicate that the activity
      of some promoters of S. Typhimurium varies on such a short time scale that these
      promoters can absorb rapid fluctuations in the direction of selection, as imposed
      during our experiment. The genomic fragments that conferred the highest levels of
      phenotypic variation were promoters controlling the synthesis of flagella, which
      are associated with virulence and host-pathogen interactions. This confirms
      earlier reports that phenotypic noise may play a role in pathogenesis and
      indicates that these promoters have among the highest levels of noise in the S.
      Typhimurium genome. This approach can be applied to many other bacterial and
      eukaryotic systems as a simple method for identifying genes with noisy
      expression.

PMID- 19096505
TI  - The Arabidopsis BLAP75/Rmi1 homologue plays crucial roles in meiotic double
      strand break repair.
AB  - In human cells and in Saccharomyces cerevisiae, BLAP75/Rmi1 acts together with
      BLM/Sgs1 and TopoIIIalpha/Top3 to maintain genome stability by limiting crossover
      (CO) formation in favour of NCO events, probably through the dissolution of
      double Holliday junction intermediates (dHJ). So far, very limited data is
      available on the involvement of these complexes in meiotic DNA repair. In this
      paper, we present the first meiotic study of a member of the BLAP75 family
      through characterisation of the Arabidopsis thaliana homologue. In A. thaliana
      blap75 mutants, meiotic recombination is initiated, and recombination progresses
      until the formation of bivalent-like structures, even in the absence of ZMM
      proteins. However, chromosome fragmentation can be detected as soon as metaphase
      I and is drastic at anaphase I, while no second meiotic division is observed.
      Using genetic and imunolocalisation studies, we showed that these defects reflect
      a role of A. thaliana BLAP75 in meiotic double-strand break (DSB) repair -- that
      it acts after the invasion step mediated by RAD51 and associated proteins and
      that it is necessary to repair meiotic DSBs onto sister chromatids as well as
      onto the homologous chromosome. In conclusion, our results show for the first
      time that BLAP75/Rmi1 is a key protein of the meiotic homologous recombination
      machinery. In A. thaliana, we found that this protein is dispensable for
      homologous chromosome recognition and synapsis but necessary for the repair of
      meiotic DSBs. Furthermore, in the absence of BLAP75, bivalent formation can
      happen even in the absence of ZMM proteins, showing that in blap75 mutants,
      recombination intermediates exist that are stable enough to form bivalent
      structures, even when ZMM are absent.

PMID- 19096506
TI  - News from Arabidopsis on the meiotic roles of Blap75/Rmi1 and Top3alpha.

PMID- 19096507
TI  - Topoisomerase 3alpha and RMI1 suppress somatic crossovers and are essential for
      resolution of meiotic recombination intermediates in Arabidopsis thaliana.
AB  - Topoisomerases are enzymes with crucial functions in DNA metabolism. They are
      ubiquitously present in prokaryotes and eukaryotes and modify the steady-state
      level of DNA supercoiling. Biochemical analyses indicate that Topoisomerase
      3alpha (TOP3alpha) functions together with a RecQ DNA helicase and a third
      partner, RMI1/BLAP75, in the resolution step of homologous recombination in a
      process called Holliday Junction dissolution in eukaryotes. Apart from that,
      little is known about the role of TOP3alpha in higher eukaryotes, as knockout
      mutants show early lethality or strong developmental defects. Using a hypomorphic
      insertion mutant of Arabidopsis thaliana (top3alpha-2), which is viable but
      completely sterile, we were able to define three different functions of the
      protein in mitosis and meiosis. The top3alpha-2 line exhibits fragmented
      chromosomes during mitosis and sensitivity to camptothecin, suggesting an
      important role in chromosome segregation partly overlapping with that of type IB
      topoisomerases. Furthermore, AtTOP3alpha, together with AtRECQ4A and AtRMI1, is
      involved in the suppression of crossover recombination in somatic cells as well
      as DNA repair in both mammals and A. thaliana. Surprisingly, AtTOP3alpha is also
      essential for meiosis. The phenotype of chromosome fragmentation, bridges, and
      telophase I arrest can be suppressed by AtSPO11 and AtRAD51 mutations, indicating
      that the protein is required for the resolution of recombination intermediates.
      As Atrmi1 mutants have a similar meiotic phenotype to Attop3alpha mutants, both
      proteins seem to be involved in a mechanism safeguarding the entangling of
      homologous chromosomes during meiosis. The requirement of AtTOP3alpha and AtRMI1
      in a late step of meiotic recombination strongly hints at the possibility that
      the dissolution of double Holliday Junctions via a hemicatenane intermediate is
      indeed an indispensable step of meiotic recombination.

PMID- 19096509
TI  - Enhancing e-health information systems with agent technology.
AB  - Agent Technology is an emerging and promising research area in software
      technology, which increasingly contributes to the development of value-added
      information systems for large healthcare organizations. Through the MediMAS
      prototype, resulting from a case study conducted at a local Swiss hospital, this
      paper aims at presenting the advantages of reinforcing such a complex E-health
      man-machine information organization with software agents. The latter will work
      on behalf of human agents, taking care of routine tasks, and thus increasing the
      speed, the systematic, and ultimately the reliability of the information
      exchanges. We further claim that the modeling of the software agent layer can be
      methodically derived from the actual "classical" laboratory organization and
      practices, as well as seamlessly integrated with the existing information system.

PMID- 19096508
TI  - Frequent toggling between alternative amino acids is driven by selection in HIV
      1.
AB  - Host immune responses against infectious pathogens exert strong selective
      pressures favouring the emergence of escape mutations that prevent immune
      recognition. Escape mutations within or flanking functionally conserved epitopes
      can occur at a significant cost to the pathogen in terms of its ability to
      replicate effectively. Such mutations come under selective pressure to revert to
      the wild type in hosts that do not mount an immune response against the epitope.
      Amino acid positions exhibiting this pattern of escape and reversion are of
      interest because they tend to coincide with immune responses that control
      pathogen replication effectively. We have used a probabilistic model of protein
      coding sequence evolution to detect sites in HIV-1 exhibiting a pattern of rapid
      escape and reversion. Our model is designed to detect sites that toggle between a
      wild type amino acid, which is susceptible to a specific immune response, and
      amino acids with lower replicative fitness that evade immune recognition. Through
      simulation, we show that this model has significantly greater power to detect
      selection involving immune escape and reversion than standard models of
      diversifying selection, which are sensitive to an overall increased rate of non
      synonymous substitution. Applied to alignments of HIV-1 protein coding sequences,
      the model of immune escape and reversion detects a significantly greater number
      of adaptively evolving sites in env and nef. In all genes tested, the model
      provides a significantly better description of adaptively evolving sites than
      standard models of diversifying selection. Several of the sites detected are
      corroborated by association between Human Leukocyte Antigen (HLA) and viral
      sequence polymorphisms. Overall, there is evidence for a large number of sites in
      HIV-1 evolving under strong selective pressure, but exhibiting low sequence
      diversity. A phylogenetic model designed to detect rapid toggling between wild
      type and escape amino acids identifies a larger number of adaptively evolving
      sites in HIV-1, and can in some cases correctly identify the amino acid that is
      susceptible to the immune response.

PMID- 19096510
TI  - Dissecting the cell entry pathway of dengue virus by single-particle tracking in
      living cells.
AB  - Dengue virus (DENV) is an enveloped RNA virus that causes the most common
      arthropod-borne infection worldwide. The mechanism by which DENV infects the host
      cell remains unclear. In this work, we used live-cell imaging and single-virus
      tracking to investigate the cell entry, endocytic trafficking, and fusion
      behavior of DENV. Simultaneous tracking of DENV particles and various endocytic
      markers revealed that DENV enters cells exclusively via clathrin-mediated
      endocytosis. The virus particles move along the cell surface in a diffusive
      manner before being captured by a pre-existing clathrin-coated pit. Upon clathrin
      mediated entry, DENV particles are transported to Rab5-positive endosomes, which
      subsequently mature into late endosomes through acquisition of Rab7 and loss of
      Rab5. Fusion of the viral membrane with the endosomal membrane was primarily
      detected in late endosomal compartments.

PMID- 19096511
TI  - Shaping skeletal growth by modular regulatory elements in the Bmp5 gene.
AB  - Cartilage and bone are formed into a remarkable range of shapes and sizes that
      underlie many anatomical adaptations to different lifestyles in vertebrates.
      Although the morphological blueprints for individual cartilage and bony
      structures must somehow be encoded in the genome, we currently know little about
      the detailed genomic mechanisms that direct precise growth patterns for
      particular bones. We have carried out large-scale enhancer surveys to identify
      the regulatory architecture controlling developmental expression of the mouse
      Bmp5 gene, which encodes a secreted signaling molecule required for normal
      morphology of specific skeletal features. Although Bmp5 is expressed in many
      skeletal precursors, different enhancers control expression in individual bones.
      Remarkably, we show here that different enhancers also exist for highly
      restricted spatial subdomains along the surface of individual skeletal
      structures, including ribs and nasal cartilages. Transgenic, null, and regulatory
      mutations confirm that these anatomy-specific sequences are sufficient to trigger
      local changes in skeletal morphology and are required for establishing normal
      growth rates on separate bone surfaces. Our findings suggest that individual
      bones are composite structures whose detailed growth patterns are built from many
      smaller lineage and gene expression domains. Individual enhancers in BMP genes
      provide a genomic mechanism for controlling precise growth domains in particular
      cartilages and bones, making it possible to separately regulate skeletal anatomy
      at highly specific locations in the body.

PMID- 19096513
TI  - Apocynin: molecular aptitudes.
AB  - Apocynin is a naturally occurring methoxy-substituted catechol, experimentally
      used as an inhibitor of NADPH-oxidase. It can decrease the production of
      superoxide (O(2)(-)) from activated neutrophils and macrophages while the ability
      of phagocytosis remains unaffected. The anti-inflammatory activity of apocynin
      has been demonstrated in a variety of cell and animal models of inflammation.
      Apocynin, after metabolic conversion, inhibits the assembly of NADPH-oxidase that
      is responsible for reactive oxygen species (ROS) production. It is, therefore,
      extensively used to reveal the role of this enzyme in cell and experimental
      models. Although some of the ROS serve as signaling molecules in the cells,
      excessive production is damaging and has been implicated to play an important
      role in the progression of many disease processes. This is why in many studies
      apocynin presents a promising potential treatment for some disorders; however,
      its utility with inflammatory diseases remains to be determined. Since its mode
      of action is not well defined, we tried to get a more precise insight into the
      mechanisms by which apocynin exerts its activity. Considering the anti
      inflammatory activities of apocynin, we may conclude that this compound
      definitely deserves further study.

PMID- 19096512
TI  - The effects of Thiazolidinediones on metabolic complications and Lipodystrophy in
      HIV-infected patients.
AB  - Highly active antiretroviral therapy (HAART)-associated metabolic complications
      include lipoatrophy (loss of subcutaneous adipose tissue (SAT)) and insulin
      resistance. Thiazolidinediones are insulin-sensitizing antidiabetic agents which
      as an untoward side effect in obese diabetic patients-increase SAT. Furthermore,
      troglitazone has improved lipoatrophy and glycemic control in non-HIV patients
      with various forms of lipodystrophy. These data have led to 14 clinical trials to
      examine whether thiazolidinediones could be useful in the treatment of HAART
      associated metabolic complications. The results of these studies indicate very
      modest, if any, effect on lipoatrophic SAT, probably due to ongoing HAART
      negating the beneficial effect. The benefit might be more prominent in patients
      not taking thymidine analoges. Despite the poor effect on lipoatrophy,
      thiazolidin-ediones improved insulin sensitivity. However, especially
      rosiglitazone induced harmful effects on blood lipids. Current data do not
      provide evidence for the use of thiazolidinediones in the treatment of HAART
      associated lipoatrophy, but treatment of lipoatrophy-associated diabetes may be
      warranted. The role of thiazolidinediones for novel indications, such as
      hepatosteatosis, should be studied in these patients.

PMID- 19096514
TI  - Antiaversive effects of cannabinoids: is the periaqueductal gray involved?
AB  - Cannabinoids play an important role in activity-dependent changes in synaptic
      activity and can interfere in several brain functions, including responses to
      aversive stimuli. The regions responsible for their effects, however, are still
      unclear. Cannabinoid type 1 (CB1) receptors are widely distributed in the central
      nervous system and are present in the periaqueductal gray (PAG), a midbrain
      structure closely involved in responses related to aversive states. Accordingly,
      exposure to stressful stimuli increases endocannabinoid (eCB) levels in the PAG,
      and local administration of CB1 agonists or drugs that facilitate eCB-mediated
      neurotransmission produces antinociceptive and antiaversive effects. To
      investigate if these drugs would also interfere in animal models that are
      sensitive to anxiolytic drugs, we verified the responses to intra-PAG injection
      of CB1 agonists in rats submitted to the elevated plus-maze, the Vogel punished
      licking test, or contextual aversive conditioning model. The drugs induced
      anxiolytic-like effects in all tests. The same was observed with the transient
      receptor potential vanilloid type 1 (TRPV1) antagonist capsazepine and with
      cannabidiol, a nonpsychotomimetic phytocannabinoid that produces anxiolytic-like
      effects after systemic administration in humans and laboratory animals. These
      results, therefore, suggest that the PAG could be an important site for the
      antiaversive effects of cannabinoids.

PMID- 19096515
TI  - Progesterone withdrawal-evoked plasticity of neural function in the female
      periaqueductal grey matter.
AB  - Cyclical changes in production of neuroactive steroids during the oestrous cycle
      induce significant changes in GABA(A) receptor expression in female rats. In the
      periaqueductal grey (PAG) matter, upregulation of alpha4beta1delta GABA(A)
      receptors occurs as progesterone levels fall during late dioestrus (LD) or during
      withdrawal from an exogenous progesterone dosing regime. The new receptors are
      likely to be extrasynaptically located on the GABAergic interneurone population
      and to mediate tonic currents. Electrophysiological studies showed that when
      alpha4beta1delta GABA(A) receptor expression was increased, the excitability of
      the output neurones in the PAG increased, due to a decrease in the level of
      ongoing inhibitory tone from the GABAergic interneurones. The functional
      consequences in terms of nociceptive processing were investigated in conscious
      rats. Baseline tail flick latencies were similar in all rats. However, acute
      exposure to mild vibration stress evoked hyperalgesia in rats in LD and after
      progesterone withdrawal, in line with the upregulation of alpha4beta1delta
      GABA(A) receptor expression.

PMID- 19096516
TI  - Comparative analysis of fatty acid desaturases in cyanobacterial genomes.
AB  - Fatty acid desaturases are enzymes that introduce double bonds into the
      hydrocarbon chains of fatty acids. The fatty acid desaturases from 37
      cyanobacterial genomes were identified and classified based upon their conserved
      histidine-rich motifs and phylogenetic analysis, which help to determine the
      amounts and distributions of desaturases in cyanobacterial species. The
      filamentous or N(2)-fixing cyanobacteria usually possess more types of fatty acid
      desaturases than that of unicellular species. The pathway of acyl-lipid
      desaturation for unicellular marine cyanobacteria Synechococcus and
      Prochlorococcus differs from that of other cyanobacteria, indicating different
      phylogenetic histories of the two genera from other cyanobacteria isolated from
      freshwater, soil, or symbiont. Strain Gloeobacter violaceus PCC 7421 was isolated
      from calcareous rock and lacks thylakoid membranes. The types and amounts of
      desaturases of this strain are distinct to those of other cyanobacteria,
      reflecting the earliest divergence of it from the cyanobacterial line. Three
      thermophilic unicellular strains, Thermosynechococcus elongatus BP-1 and two
      Synechococcus Yellowstone species, lack highly unsaturated fatty acids in lipids
      and contain only one Delta9 desaturase in contrast with mesophilic strains, which
      is probably due to their thermic habitats. Thus, the amounts and types of fatty
      acid desaturases are various among different cyanobacterial species, which may
      result from the adaption to environments in evolution.

PMID- 19096517
TI  - Botulinum neurotoxin devoid of receptor binding domain translocates active
      protease.
AB  - Clostridium botulinum neurotoxin (BoNT) causes flaccid paralysis by disabling
      synaptic exocytosis. Intoxication requires the tri-modular protein to undergo
      conformational changes in response to pH and redox gradients across endosomes,
      leading to the formation of a protein-conducting channel. The approximately 50
      kDa light chain (LC) protease is translocated into the cytosol by the
      approximately 100 kDa heavy chain (HC), which consists of two modules: the N
      terminal translocation domain (TD) and the C-terminal Receptor Binding Domain
      (RBD). Here we exploited the BoNT modular design to identify the minimal
      requirements for channel activity and LC translocation in neurons. Using the
      combined detection of substrate proteolysis and single-channel currents, we
      showed that a di-modular protein consisting only of LC and TD was sufficient to
      translocate active protease into the cytosol of target cells. The RBD is
      dispensable for cell entry, channel activity, or LC translocation; however, it
      determined a pH threshold for channel formation. These findings indicate that, in
      addition to its individual functions, each module acts as a chaperone for the
      others, working in concert to achieve productive intoxication.

PMID- 19096518
TI  - Novel association of HK1 with glycated hemoglobin in a non-diabetic population: a
      genome-wide evaluation of 14,618 participants in the Women's Genome Health Study.
AB  - Type 2 diabetes is a leading cause of morbidity and mortality. While genetic
      variants have been found to influence the risk of type 2 diabetes mellitus,
      relatively few studies have focused on genes associated with glycated hemoglobin,
      an index of the mean blood glucose concentration of the preceding 8-12 weeks.
      Epidemiologic studies and randomized clinical trials have documented the
      relationship between glycated hemoglobin levels and the development of long-term
      complications in diabetes; moreover, higher glycated hemoglobin levels in the
      subdiabetic range have been shown to predict type 2 diabetes risk and
      cardiovascular disease. To examine the common genetic determinants of glycated
      hemoglobin levels, we performed a genome-wide association study that evaluated
      337,343 SNPs in 14,618 apparently healthy Caucasian women. The results show that
      glycated hemoglobin levels are associated with genetic variation at the GCK
      (rs730497; P = 2.8 x 10(-12)), SLC30A8 (rs13266634; P = 9.8 x 10(-8)), G6PC2
      (rs1402837; P = 6.8 x 10(-10)), and HK1 (rs7072268; P = 6.4 x 10(-9)) loci. While
      associations at the GCK, SLC30A8, and G6PC2 loci are confirmatory, the findings
      at HK1 are novel. We were able to replicate this novel association in an
      independent validation sample of 455 additional non-diabetic men and women. HK1
      encodes the enzyme hexokinase, the first step in glycolysis and a likely
      candidate for the control of glucose metabolism. This observed genetic
      association between glycated hemoglobin levels and HK1 polymorphisms paves the
      way for further studies of the role of HK1 in hemoglobin glycation, glucose
      metabolism, and diabetes.

PMID- 19096520
TI  - Reductive evolution of the mitochondrial processing peptidases of the unicellular
      parasites trichomonas vaginalis and giardia intestinalis.
AB  - Mitochondrial processing peptidases are heterodimeric enzymes (alpha/betaMPP)
      that play an essential role in mitochondrial biogenesis by recognizing and
      cleaving the targeting presequences of nuclear-encoded mitochondrial proteins.
      The two subunits are paralogues that probably evolved by duplication of a gene
      for a monomeric metallopeptidase from the endosymbiotic ancestor of mitochondria.
      Here, we characterize the MPP-like proteins from two important human parasites
      that contain highly reduced versions of mitochondria, the mitosomes of Giardia
      intestinalis and the hydrogenosomes of Trichomonas vaginalis. Our biochemical
      characterization of recombinant proteins showed that, contrary to a recent
      report, the Trichomonas processing peptidase functions efficiently as an
      alpha/beta heterodimer. By contrast, and so far uniquely among eukaryotes, the
      Giardia processing peptidase functions as a monomer comprising a single betaMPP
      like catalytic subunit. The structure and surface charge distribution of the
      Giardia processing peptidase predicted from a 3-D protein model appear to have co
      evolved with the properties of Giardia mitosomal targeting sequences, which,
      unlike classic mitochondrial targeting signals, are typically short and
      impoverished in positively charged residues. The majority of hydrogenosomal
      presequences resemble those of mitosomes, but longer, positively charged
      mitochondrial-type presequences were also identified, consistent with the
      retention of the Trichomonas alphaMPP-like subunit. Our computational and
      experimental/functional analyses reveal that the divergent processing peptidases
      of Giardia mitosomes and Trichomonas hydrogenosomes evolved from the same
      ancestral heterodimeric alpha/betaMPP metallopeptidase as did the classic
      mitochondrial enzyme. The unique monomeric structure of the Giardia enzyme, and
      the co-evolving properties of the Giardia enzyme and substrate, provide a
      compelling example of the power of reductive evolution to shape parasite biology.

PMID- 19096519
TI  - Sexually antagonistic "zygotic drive" of the sex chromosomes.
AB  - Genomic conflict is perplexing because it causes the fitness of a species to
      decline rather than improve. Many diverse forms of genomic conflict have been
      identified, but this extant tally may be incomplete. Here, we show that the
      unusual characteristics of the sex chromosomes can, in principle, lead to a
      previously unappreciated form of sexual genomic conflict. The phenomenon occurs
      because there is selection in the heterogametic sex for sex-linked mutations that
      harm the sex of offspring that does not carry them, whenever there is competition
      among siblings. This harmful phenotype can be expressed as an antagonistic green
      beard effect that is mediated by epigenetic parental effects, parental
      investment, and/or interactions among siblings. We call this form of genomic
      conflict sexually antagonistic "zygotic drive", because it is functionally
      equivalent to meiotic drive, except that it operates during the zygotic and
      postzygotic stages of the life cycle rather than the meiotic and gametic stages.
      A combination of mathematical modeling and a survey of empirical studies is used
      to show that sexually antagonistic zygotic drive is feasible, likely to be
      widespread in nature, and that it can promote a genetic "arms race" between the
      homo- and heteromorphic sex chromosomes. This new category of genomic conflict
      has the potential to strongly influence other fundamental evolutionary processes,
      such as speciation and the degeneration of the Y and W sex chromosomes. It also
      fosters a new genetic hypothesis for the evolution of enigmatic fitness-reducing
      traits like the high frequency of spontaneous abortion, sterility, and
      homosexuality observed in humans.

PMID- 19096521
TI  - Genetic and computational identification of a conserved bacterial metabolic
      module.
AB  - We have experimentally and computationally defined a set of genes that form a
      conserved metabolic module in the alpha-proteobacterium Caulobacter crescentus
      and used this module to illustrate a schema for the propagation of pathway-level
      annotation across bacterial genera. Applying comprehensive forward and reverse
      genetic methods and genome-wide transcriptional analysis, we (1) confirmed the
      presence of genes involved in catabolism of the abundant environmental sugar myo
      inositol, (2) defined an operon encoding an ABC-family myo-inositol transmembrane
      transporter, and (3) identified a novel myo-inositol regulator protein and cis
      acting regulatory motif that control expression of genes in this metabolic
      module. Despite being encoded from non-contiguous loci on the C. crescentus
      chromosome, these myo-inositol catabolic enzymes and transporter proteins form a
      tightly linked functional group in a computationally inferred network of protein
      associations. Primary sequence comparison was not sufficient to confidently
      extend annotation of all components of this novel metabolic module to related
      bacterial genera. Consequently, we implemented the Graemlin multiple-network
      alignment algorithm to generate cross-species predictions of genes involved in
      myo-inositol transport and catabolism in other alpha-proteobacteria. Although the
      chromosomal organization of genes in this functional module varied between
      species, the upstream regions of genes in this aligned network were enriched for
      the same palindromic cis-regulatory motif identified experimentally in C.
      crescentus. Transposon disruption of the operon encoding the computationally
      predicted ABC myo-inositol transporter of Sinorhizobium meliloti abolished growth
      on myo-inositol as the sole carbon source, confirming our cross-genera functional
      prediction. Thus, we have defined regulatory, transport, and catabolic genes and
      a cis-acting regulatory sequence that form a conserved module required for myo
      inositol metabolism in select alpha-proteobacteria. Moreover, this study
      describes a forward validation of gene-network alignment, and illustrates a
      strategy for reliably transferring pathway-level annotation across bacterial
      species.

PMID- 19096523
TI  - Statistical significance of precisely repeated intracellular synaptic patterns.
AB  - Can neuronal networks produce patterns of activity with millisecond accuracy? It
      may seem unlikely, considering the probabilistic nature of synaptic transmission.
      However, some theories of brain function predict that such precision is feasible
      and can emerge from the non-linearity of the action potential generation in
      circuits of connected neurons. Several studies have presented evidence for and
      against this hypothesis. Our earlier work supported the precision hypothesis,
      based on results demonstrating that precise patterns of synaptic inputs could be
      found in intracellular recordings from neurons in brain slices and in vivo. To
      test this hypothesis, we devised a method for finding precise repeats of activity
      and compared repeats found in the data to those found in surrogate datasets made
      by shuffling the original data. Because more repeats were found in the original
      data than in the surrogate data sets, we argued that repeats were not due to
      chance occurrence. Mokeichev et al. (2007) challenged these conclusions, arguing
      that the generation of surrogate data was insufficiently rigorous. We have now
      reanalyzed our previous data with the methods introduced from Mokeichev et al.
      (2007). Our reanalysis reveals that repeats are statistically significant, thus
      supporting our earlier conclusions, while also supporting many conclusions that
      Mokeichev et al. (2007) drew from their recent in vivo recordings. Moreover, we
      also show that the conditions under which the membrane potential is recorded
      contributes significantly to the ability to detect repeats and may explain
      conflicting results. In conclusion, our reevaluation resolves the methodological
      contradictions between Ikegaya et al. (2004) and Mokeichev et al. (2007), but
      demonstrates the validity of our previous conclusion that spontaneous network
      activity is non-randomly organized.

PMID- 19096522
TI  - CD8+ T-cell interleukin-7 receptor alpha expression as a potential indicator of
      disease status in HIV-infected children.
AB  - BACKGROUND: Initiation and modification of antiretroviral therapy in HIV-infected
      children depend on viral load and CD4+ T-cell count. However, these surrogates
      have limitations, and complementary immunological markers to assess therapeutic
      response are needed. Our aim was to evaluate CD8+ T-cell expression of CD127 as a
      marker of disease status in HIV-infected children, based on adult data suggesting
      its usefulness. We hypothesized that CD127 expression on CD8+ T-cells is lower in
      children with more advanced disease. METHODS: In a cross-sectional evaluation, we
      used flow cytometry to measure CD127+ expression on CD8+ T-cells in whole blood
      from HIV-infected children with varying disease status. This was compared with
      expression of CD38 on this subset, currently used in clinical practice as a
      marker of disease status. RESULTS: 51 HIV-infected children were enrolled. There
      was a strong positive correlation between CD127 expression on CD8+ T-cells and
      CD4+ T-cell count, and height and weight z-scores, and a strong negative
      correlation between CD127 expression and viral load. In contrast, we found no
      association between CD38 expression and these disease status markers.
      CONCLUSIONS: CD8+ T-cell CD127 expression is significantly higher in children
      with better HIV disease control, and may have a role as an immunologic indicator
      of disease status. Longitudinal studies are needed to determine the utility of
      this marker as a potential indicator of HIV disease progression.

PMID- 19096524
TI  - Liver resections combined with closure of loop ileostomies: a retrospective
      analysis.
AB  - BACKGROUND: The management of patients with colorectal liver metastases and loop
      ileostomies remains controversial. This study was performed to assess the outcome
      of combined liver resection and loop ileostomy closure. METHODS: Analysis of
      prospectively collected perioperative data, including morbidity and mortality, of
      283 consecutive hepatectomies for colorectal liver metastases was undertaken.
      Consecutive liver resections were performed from 1996 to 2006 in one centre by a
      single surgeon (NDK). Fourteen of these patients had combined liver resection and
      ileostomy closure. Case-matched analysis was undertaken. RESULTS: Six (2.2%)
      patients died in the hepatectomy only group and none died in the combined group.
      There was no difference in operative blood loss between the two groups (0.09).
      Perioperative morbidity was 36% in the combined group and 23% in the hepatectomy
      alone group (P = 0.33). Mean hospital stay was 14 days in the combined group and
      11 days in the hepatectomy only group (P = 0.046). Case-matched analysis showed a
      significant increase in hospital stay (P = 0.03) and complications (P = 0.049) in
      the combined group. CONCLUSION: In patients with CRLM, combined liver resection
      and closure of ileostomy may be associated with a higher operative morbidity and
      a prolonged hospital stay.

PMID- 19096525
TI  - Comprehensive management of upper tract urothelial carcinoma.
AB  - Urothelial carcinoma of the upper urinary tract represents only 5% of all
      urothelial cancers. The 5-year cancer-specific survival in the United States is
      roughly 75% with grade and stage being the most powerful predictors of survival.
      Nephroureterectomy with excision of the ipsilateral ureteral orifice and bladder
      cuff en bloc remains the gold standard treatment of the upper urinary tract
      urothelial cancers, while endoscopic and laparoscopic approaches are rapidly
      evolving as reasonable alternatives of care depending on grade and stage of
      disease. Several controversies remain in their management, including a selection
      of endoscopic versus laparoscopic approaches, management strategies on the distal
      ureter, the role of lymphadenectomy, and the value of chemotherapy in upper tract
      disease. Aims of this paper are to critically review the management of such
      tumors, including endoscopic management, laparoscopic nephroureterectomy and
      management of the distal ureter, the role of lymphadenectomy, and the emerging
      role of chemotherapy in their treatment.

PMID- 19096526
TI  - Ir-LBP, an ixodes ricinus tick salivary LTB4-binding lipocalin, interferes with
      host neutrophil function.
AB  - BACKGROUND: During their blood meal, ticks secrete a wide variety of proteins
      that can interfere with their host's defense mechanisms. Among these proteins,
      lipocalins play a major role in the modulation of the inflammatory response.
      METHODOLOGY/PRINCIPAL FINDINGS: We previously identified 14 new lipocalin genes
      in the tick Ixodes ricinus. One of them codes for a protein that specifically
      binds leukotriene B4 with a very high affinity (Kd: +/-1 nM), similar to that of
      the neutrophil transmembrane receptor BLT1. By in silico approaches, we modeled
      the 3D structure of the protein and the binding of LTB4 into the ligand pocket.
      This protein, called Ir-LBP, inhibits neutrophil chemotaxis in vitro and delays
      LTB4-induced apoptosis. Ir-LBP also inhibits the host inflammatory response in
      vivo by decreasing the number and activation of neutrophils located at the tick
      bite site. Thus, Ir-LBP participates in the tick's ability to interfere with
      proper neutrophil function in inflammation. CONCLUSIONS/SIGNIFICANCE: These
      elements suggest that Ir-LBP is a "scavenger" of LTB4, which, in combination with
      other factors, such as histamine-binding proteins or proteins inhibiting the
      classical or alternative complement pathways, permits the tick to properly manage
      its blood meal. Moreover, with regard to its properties, Ir-LBP could possibly be
      used as a therapeutic tool for illnesses associated with an increased LTB4
      production.

PMID- 19096527
TI  - Protective antiviral immunity conferred by a nonintegrative lentiviral vector
      based vaccine.
AB  - Lentiviral vectors are under intense scrutiny as unique candidate viral vector
      vaccines against tumor and aggressive pathogens because of their ability to
      initiate potent and durable specific immune responses. Strategies that alleviate
      safety concerns will facilitate the clinical developments involving lentiviral
      vectors. In this respect, the development of integration deficient lentiviral
      vectors circumvents the safety concerns relative to insertional mutagenesis and
      might pave the way for clinical applications in which gene transfer is targeted
      to non-dividing cells. We thus evaluated the potential use of nonintegrative
      lentiviral vectors as vaccination tools since the main targeted cell in
      vaccination procedures is the non-dividing dendritic cell (DC). In this study, we
      demonstrated that a single administration of nonintegrative vectors encoding a
      secreted form of the envelope of a virulent strain of West Nile Virus (WNV)
      induces a robust B cell response. Remarkably, nonintegrative lentiviral vectors
      fully protected mice from a challenge with a lethal dose of WNV and a single
      immunization was sufficient to induce early and long-lasting protective immunity.
      Thus, nonintegrative lentiviral vectors might represent a safe and efficacious
      vaccination platform for the development of prophylactic vaccines against
      infectious agents.

PMID- 19096529
TI  - Inter-Rater Reliability of the Diagnoses of Psychosis and Depression in
      Individuals with Intellectual Disabilities.
AB  - BACKGROUND: There is a history of over-prescription of antipsychotics to
      individuals with intellectual disability (ID), while antidepressants may be under
      prescribed. However, appropriate treatment is best supported when the diagnosis
      of psychosis or depression is valid and carries good predictive validity. The
      present authors report a study examining one aspect of validity, namely whether
      skilled clinicians can agree on whether an individual with an ID is psychotic or
      depressed. MATERIALS AND METHODS: Pairs of clinicians assessed 52 individuals.
      Agreement was assessed using Cohen's kappa statistic and agreement proportion.
      RESULTS: Overall agreement was high for both psychosis and depression. Whether
      the individual had mild ID or moderate/severe ID did not have a significant
      impact on agreement. CONCLUSIONS: Experienced clinicians achieved a high level of
      agreement as to whether a person with ID was psychotic or depressed similar to
      that found for those without ID. The findings provide some support for treatment
      interventions based on diagnosis.

PMID- 19096528
TI  - Polymorphism of DCDC2 Reveals Differences in Cortical Morphology of Healthy
      Individuals-A Preliminary Voxel Based Morphometry Study.
AB  - OBJECTIVE: The purpose of this investigation was to determine whether there is an
      association between the putative reading disability (RD) susceptibility gene
      Doublecortin Domain Containing 2 (DCDC2), and gray matter (GM) distribution in
      the brain, in a sample of healthy control individuals. METHOD: Fifty-six control
      subjects were genotyped for an RD-associated deletion in intron 2 of DCDC2. Voxel
      based morphometry (VBM) was used to examine structural magnetic resonance imaging
      (MRI) scans to assess GM differences between the two groups. RESULTS: Individuals
      heterozygous for the deletion exhibited significantly higher GM volumes in
      reading/language and symbol-decoding related brain regions including superior,
      medial and inferior temporal, fusiform, hippocampal/para-hippocampal, inferior
      occipito-parietal, inferior and middle frontal gyri, especially in the left
      hemisphere. GM values correlated with published data on regional DCDC2 expression
      in a lateralized manner. CONCLUSIONS: These data suggest a role for DCDC2 in GM
      distribution in language-related brain regions in healthy individuals.

PMID- 19096530
TI  - Flux Tensor Constrained Geodesic Active Contours with Sensor Fusion for
      Persistent Object Tracking.
AB  - This paper makes new contributions in motion detection, object segmentation and
      trajectory estimation to create a successful object tracking system. A new
      efficient motion detection algorithm referred to as the flux tensor is used to
      detect moving objects in infrared video without requiring background modeling or
      contour extraction. The flux tensor-based motion detector when applied to
      infrared video is more accurate than thresholding "hot-spots", and is insensitive
      to shadows as well as illumination changes in the visible channel. In real world
      monitoring tasks fusing scene information from multiple sensors and sources is a
      useful core mechanism to deal with complex scenes, lighting conditions and
      environmental variables. The object segmentation algorithm uses level set-based
      geodesic active contour evolution that incorporates the fusion of visible color
      and infrared edge informations in a novel manner. Touching or overlapping objects
      are further refined during the segmentation process using an appropriate shape
      based model. Multiple object tracking using correspondence graphs is extended to
      handle groups of objects and occlusion events by Kalman filter-based cluster
      trajectory analysis and watershed segmentation. The proposed object tracking
      algorithm was successfully tested on several difficult outdoor multispectral
      videos from stationary sensors and is not confounded by shadows or illumination
      variations.

PMID- 19096535
TI  - Erratum.
AB  - This corrects the article on p. e1000281 in Vol. 4, PMID: 19043566. Hypermutable
      Non-Synonymous Sites Are Under Stronger Negative Selection.

PMID- 19096531
TI  - Optineurin coding variants in Ghanaian patients with primary open-angle glaucoma.
AB  - PURPOSE: Coding variants in the optineurin gene (OPTN, GLC1E) have been reported
      to play a role in primary open-angle glaucoma (POAG) in various populations. This
      study investigated the role of OPTN sequence variants in patients with POAG in
      Ghana (West Africa). METHODS: This is a case-control study of unrelated Ghanaian
      POAG cases and non-glaucomatous controls. Ascertainment criteria for POAG
      included the presence of glaucomatous optic nerve neuropathy, associated visual
      field loss, and elevated intraocular pressure (IOP) in both eyes, all in the
      absence of secondary causes of glaucoma. Controls had normal optic nerves, visual
      fields, and IOP. All the coding exons of OPTN were polymerase chain reaction
      (PCR) amplified and sequenced in all 140 cases and 130 controls using an ABI 3730
      DNA analyzer. RESULTS: All the coding exons of OPTN were sequenced in 140 POAG
      patients and 130 controls. Several coding variants were identified including
      M98K, A134A, V147L, P292P, A301G, S321S, and E322K. Three coding variants (V147L,
      P292P, and A301G) have not been reported previously. There were no significant
      differences on the frequencies of all the identified variants between POAG cases
      and controls in this population. CONCLUSIONS: This is the first comprehensive
      study of OPTN in a single West African population. Our results suggest that
      coding variants in OPTN may not contribute to the risk for POAG in persons of
      West African descent.

PMID- 19096536
TI  - Proposal for the promotion of korean neurosurgery.
AB  - The author conducted a survey on the current status of neurosurgery around the
      world in preparation for Presidential Address at the International Society for
      Pediatric Neurosurgery (ISPN). The addresses and findings from the survey were
      presented at ISPN in 2006 and Child's Nervous System in 2007. After reviewing the
      current status of neurosurgery of various countries, the author would like to
      share this information with members of the Korean Neurosurgical Society, as well
      as offer a proposal to promote Korean neurosurgery around the world.

PMID- 19096537
TI  - Anterior interbody grafting and instrumentation for advanced spondylodiscitis.
AB  - OBJECTIVE: To evaluate the surgical outcomes of ventral interbody grafting and
      anterior or posterior spinal instrumentation for the treatment of advanced
      spondylodiscitis in patients who had failed medical management. METHODS: A total
      of 28 patients were evaluated for associated medical illness, detected pathogen,
      level of involved spine, and perioperative complications. Radiological evaluation
      including the rate of bony union, segmental Cobb angle, graft- and
      instrumentation-related complications, and clinical outcomes by mean Frankel
      scale and VAS score were performed. RESULTS: There are 14 pyogenic
      spondylodiscitis, 6 postoperative spondylodiscitis, and 8 tuberculous
      spondylodiscitis. There were 21 males and 7 females. Mean age was 51 years, with
      a range from 18 to 77. Mean follow-up period was 10.9 months. Associated medical
      illnesses were 6 diabetes, 3 pulmonary tuberculosis, and 4 chronic liver
      diseases. Staphylococcus was the most common pathogen isolated (25%), and
      Mycobacterium tuberculosis was found in 18% of the patients. Operative
      approaches, either anterior or posterior spinal instrumentation, were done
      simultaneously or delayed after anterior aggressive debridement, neural
      decompression, and structural interbody bone grafting. All patients with
      neurological deficits improved after operation, except only one who died from
      aggravation as military tuberculosis. Mean Frankel scale was changed from 3.78+/
      0.78 preoperatively to 4.78+/-0.35 at final follow up and mean VAS score was
      improved from 7.43+/-0.54 to 2.07+/-1.12. Solid bone fusion was obtained in all
      patients except only one patient who died. There was no need for prolongation of
      duration of antibiotics and no evidence of secondary infection owing to spinal
      instrumentations. CONCLUSION: According to these results, debridement and
      anterior column reconstruction with ventral interbody grafting and
      instrumentation is effective and safe in patients who had failed medical
      management and neurological deficits in advanced spondylodiscitis.

PMID- 19096538
TI  - Clinical analysis of risk factors related to recurrent chronic subdural hematoma.
AB  - OBJECTIVE: Burr hole drainage has been widely used to treat chronic subdural
      hematoma (CSDH). However, the incidence of recurrent CSDH varies from 3.7 to 30%
      after surgery. The authors attempted to elucidate the risk factors associated
      with the recurrence of CSDH in one burr hole drainage technique. METHODS: A total
      of 255 consecutive cases who underwent one burr hole drainage for CSDH were
      included in this study. Twenty-four patients (9.4%) underwent a repeated
      operation because of the recurrence of CSDH. We analyzed retrospectively the
      demographic, clinical and radiologic factors associated with the recurrence of
      CSDH. RESULTS: In this study, two risk factors were found to be independently
      associated with the recurrence of CSDH. The incidence of CSDH recurrence in the
      high- and mixed-density groups was significantly higher than those in the low-
      and iso-density groups (p<0.001). Bleeding tendency such as in leukemia, liver
      disease and chronic renal failure was also significantly associated with
      recurrence of CSDH (p=0.037). CONCLUSION: These results suggest that high- and
      mixed- density shown on computed tomographic scan was closely relates with a high
      incidence of recurrence. Therefore, the operation could be delayed in those cases
      unless severe symptoms or signs are present. Reoperation using the previous burr
      hole site is a preferred modality to treat the recurrent CSDH.

PMID- 19096539
TI  - Recent epidemiological trends of stroke.
AB  - OBJECTIVE: Rapid increase in aged population and westernization of lifestyle have
      modified epidemiological status of stroke. The purpose of this study is to
      analyze changing trends of stroke epidemiology in South Korea. METHODS: We
      reviewed retrospectively medical records of 1,124 cases diagnosed as stroke among
      54,534 patients who visited the Emergency Medical Center at our hospital from
      January 1994 to December 1996 (Group A). Also, we evaluated 1,705 cases diagnosed
      as stroke among 55,381 patients who visited to the same hospital from January
      2003 to December 2005 (Group B). The variable features of stroke, such as age,
      sex, seasonal variation and distribution of stroke subtypes were studied by
      comparing group A with B. RESULTS: In group A, hemorrhagic stroke (67.9%) was
      more prevalent than ischemic stroke (32.1%). However, group B showed that the
      ratio of hemorrhagic stroke (40.3%) to ischemic stroke (59.6%) has been reversed.
      The highest incidence of stroke was noted in their sixties and seventies of age
      in group B, which was older than that of group A. In group A, male ischemic
      stroke (IS) patients outnumbered female patients (1.26:1). Moreover, this gender
      disproportion became higher in group B (1.53:1). In group A, the number of male
      intracerebral hermorrhage (ICH) patients were similar to that of female patients
      (0.97:1). However, male ICH patients outnumbered female patients in group B
      (1.23:1). As for subarachnoid hemorrhage (SAH), female patients outnumbered male
      patients more than two-fold in both groups. Both groups showed that the
      occurrence of ischemic stroke was highest in summer, but that of hemorrhagic
      stroke was the highest in winter. CONCLUSION: This study showed the changing
      trends of stroke in its distribution of subtypes. Multicenter prospective study
      using stroke registry would be required for the determination of national
      epidemiologic trends.

PMID- 19096540
TI  - Combined endovascular and microsurgical procedures as complementary approaches in
      the treatment of a single intracranial aneurysm.
AB  - OBJECTIVE: Both endovascular coil embolization and microsurgical clipping are now
      firmly established as treatment options for the management of cerebral aneurysms.
      Moreover, they are sometimes used as complementary approaches each other. This
      study retrospectively analyzed our experience with endovascular and microsurgical
      procedures as complementary approaches in treating a single aneurysm. METHODS:
      Nineteen patients with intracranial aneurysm were managed with both endovascular
      and microsurgical treatments. All of the aneurysms were located in the anterior
      circulation. Eighteen patients presented with SAH, and 14 aneurysms had diameters
      of less than 10 mm, and five had diameters of 10-25 mm. RESULTS: Thirteen of the
      19 patients were initially treated with endovascular coil embolization, followed
      by microsurgical management. Of the 13 patients, 9 patients had intraprocedural
      complications during coil embolization (intraprocedural rupture, coil protrusion,
      coil migration), rebleeding with regrowth of aneurysm in two patients, residual
      sac in one patient, and coil compaction in one patient. Six patients who had
      undergone microsurgical clipping were followed by coil embolization because of a
      residual aneurysm sac in four patients, and regrowth in two patients. CONCLUSION:
      In intracranial aneurysms involving procedural endovascular complications or
      incomplete coil embolization and failed microsurgical clipping, because of
      anatomical and/or technical difficulties, the combined and complementary therapy
      with endovascular coiling and microsurgical clipping are valuable in providing
      the best outcome.

PMID- 19096541
TI  - Development of a stereotactic device for gamma knife irradiation of small
      animals.
AB  - OBJECTIVE: The authors developed a stereotactic device for irradiation of small
      animals with Leksell Gamma Knife(R) Model C. Development and verification
      procedures were described in this article. METHODS: The device was designed to
      satisfy three requirements. The mechanical accuracy in positioning was to be
      managed within 0.5 mm. The strength of the device and structure were to be
      compromised to provide enough strength to hold a small animal during irradiation
      and to interfere the gamma ray beam as little as possible. The device was to be
      used in combination with the Leksell G-frame(R) and KOPF(R) rat adaptor. The
      irradiation point was determined by separate imaging sequences such as plain X
      ray images. RESULTS: The absolute dose rate with the device in a Leksell Gamma
      Knife was 3.7% less than the value calculated from Leksell Gamma Plan(R). The
      dose distributions measured with GAFCHROMIC(R) MD-55 film corresponded to those
      of Leksell Gamma Plan(R) within acceptable range. The device was used in a series
      of rat experiments with a 4 mm helmet of Leksell Gamma Knife. CONCLUSION: A
      stereotactic device for irradiation of small animals with Leksell Gamma Knife
      Model C has been developed so that it fulfilled above requirements. Absorbed dose
      and dose distribution at the center of a Gamma Knife helmet are in acceptable
      ranges. The device provides enough accuracy for stereotactic irradiation with
      acceptable practicality.

PMID- 19096542
TI  - Transverse fracture and dislocation at the sacrum.
AB  - We present a rare case of fracture-dislocation at the level of the first sacral
      (S1) and second sacral (S2) vertebrae. The S1 was displaced forward into the
      pelvic cavity and was located just in front of the S2. Because the patient also
      had extensive neurological injury to the lumbar plexus and instability of the
      pelvic ring, surgery to stabilize the pelvis and to decompress the lumbar plexus
      was performed. The surgery was successful and the patient experienced marked
      improvement in neurological function.

PMID- 19096543
TI  - An osteolytic meningioma en plaque of the sphenoid ridge.
AB  - Meningioma en plaque (MEP) is a rare tumor characterized more by its clinical and
      biological behavior than its histological appearance. Hyperostosis of the skull
      is one of the characteristic signs of MEP. This bony change can produce clinical
      symptoms and signs in MEP by pressing against adjacent structures. The authors
      report a rare case of an osteolytic MEP extending from the sphenoid wing into the
      orbital wall, middle fossa, and temporalis muscle.

PMID- 19096544
TI  - A case of spondylodiscitis with spinal epidural abscess due to Brucella.
AB  - Brucellosis, a zoonosis with worldwide distribution, is a systemic infection
      caused by facultative intracellular bacteria of the genus Brucella, which can
      involve multiple organs and tissues. We report an uncommon case of
      spondylodiscitis with epidural abscess due to Brucella in a male stockbreeder.
      Diagnosis was based on clinical history, and supported by Brucella serology and
      magnetic resonance imaging. Clinical and radiological improvement were observed
      with a combined antimicrobial therapy of doxycycline, rifampicin, and gentamycin.

PMID- 19096545
TI  - Coil Embolization of Aneurysm Followed by Stereotactic Aspiration of Hematoma in
      a Patient with Anterior Communicating Artery Aneurysm Presenting with SAH and
      ICH.
AB  - Even though intracerebral hematoma (ICH) due to ruptured cerebral aneurysm has
      been treated by aneurysm clipping at the same time of removal of ICH through
      craniotomy, such management strategy is controversial in an aged patients with
      poor clinical grade. In this regards, stereotactic aspiration of hematoma
      following coil embolization can be an alternative treatment modality. Thus, the
      authors report a case of an aged patient who underwent stereotactic aspiration of
      ICH following coil embolization for the ruptured aneurysm with a brief review of
      literature.

PMID- 19096546
TI  - Cervical spondylodiscitis caused by Candida albicans in non-immunocompromised
      patient.
AB  - Fungal infections of the spine are relatively uncommon. Moreover, cervical
      spondylodiscitis due to Candida albicans in non-immunocompromised patient is very
      rare. We report a case of Candida spondylodiscitis in a 64-year-old woman who
      complained of neck pain. The clinical feature and treatment option are presented
      with a review of pertinent literatures.

PMID- 19096547
TI  - Giant arachnoid granulation misdiagnosed as transverse sinus thrombosis.
AB  - We experienced a case of giant arachnoid granulation misdiagnosed as dural sinus
      thrombosis. A 66-year-old woman presented with a one month history of progressive
      occipital headache. Computed tomography angiography and cerebral angiography
      showed a round filling defect at the transverse sinus which was speculated as a
      transverse sinus thrombosis. Anticoagulation therapy was performed to prevent
      worsening of thrombosis for 2 weeks and then a Gadolinium-enhanced magnetic
      resonance imaging scan was performed. The filling defect lesion at the transverse
      sinus revealed a non-enhancing granule with central linear enhancement, which was
      compatible with giant arachnoid granulation. We checked the intrasinus pressure
      difference across the lesion the through the dural sinus in order to exclude the
      lesion as the cause of headache. Normal venous pressure with no significant
      differential pressure across the lesion was noted. Headache was treated with
      medical therapy.

PMID- 19096548
TI  - "Syndrome of the sinking skin-flap" secondary to the ventriculoperitoneal shunt
      after craniectomy.
AB  - The syndrome of the sinking skin flap was introduced to explain the phenomenon of
      neurological deterioration after decompressive craniectomy. A 37-year-old man was
      admitted with acute subdural hematoma and traumatic intraparenchymal hematoma.
      After decompressive craniectomy, the patient suffered from hydrocephalus for
      which a ventriculoperitoneal (V-P) shunt was inserted. Following this procedure,
      the depression of the skin flap became remarkable and his mentation was
      deteriorated. The patient recovered uneventfully after temporary elevating of
      valve pressure and cranioplasty. We present a patient who was successfully
      managed with elevation of valve pressure and cranioplasty for the syndrome of the
      sinking scalp flap with review of a pertinent literature.

PMID- 19096549
TI  - Arachnoid cyst with spontaneous intracystic hemorrhage and chronic subdural
      hematoma.
AB  - We report a case of arachnoid cyst in which subdural hematoma and intracystic
      hemorrhage developed spontaneously. Usually, arachnoid cysts are asymptomatic,
      but can become symptomatic because of cyst enlargement or hemorrhage, often after
      mild head trauma. Although they are sometimes combined with subdural hematoma,
      intracystic hemorrhage has rarely been observed. Our patient had a simultaneous
      subdural hematoma and intracystic hemorrhage without evidence of head trauma.

PMID- 19096550
TI  - Staging in vestibular schwannoma surgery: a modified technique.
AB  - The authors herein propose the staged excision as a novel strategy to preserve
      facial nerve and minimize complication during microsurgery of large vestibular
      schwannoma (VS). At the first stage, for reducing mass effect on the brain stem
      and cerebellum, subtotal tumor resection was performed via a retrosigmoid
      craniotomy without intervention of meatal portion of tumor. With total resection
      of the remaining tumor, the facial nerve was decompressed and delineated during
      the second stage translabyrinthine approach at a later date. A 38-year-old female
      who underwent the staging operation for resection of her huge VS is illustrated.

PMID- 19096551
TI  - Clinical applications of the tubular retractor on spinal disorders.
AB  - Tubular retractor system as a minimally invasive surgery (MIS) technique has many
      advantages over other conventional MIS techniques. It offers direct visualization
      of the operative field, anatomical familiarity to spine surgeons, and minimizing
      tissue trauma. With technical advancement, many spinal pathologies are being
      treated using this system. Namely, herniated discs, lumbar and cervical stenosis,
      synovial cysts, lumbar instability, trauma, and even some intraspinal tumors have
      all been treated through tubular retractor system. Flexible arm and easy change
      of the tube direction are particularly useful in contralateral spinal
      decompression from an ipsilateral approach. Careful attention to surgical
      technique through narrow space will ensure that complications are minimized and
      will provide improved outcomes. However, understanding detailed anatomies and
      keeping precise surgical orientation are essential for this technique. Authors
      present the technical feasibility and initial results of use a tubular retractor
      system as a minimally invasive technique for variaties of spinal disorders with a
      review of literature.

PMID- 19096552
TI  - A Multi-center Clinical Study of Posterior Lumbar Interbody Fusion with the
      Expandable Stand-alone Cage (Tyche(R) Cage) for Degenerative Lumbar Spinal
      Disorders.
AB  - OBJECTIVE: This multi-center clinical study was designed to determine the long
      term results of patients who received a one-level posterior lumbar interbody
      fusion with expandable cage (Tyche(R) cage) for degenerative spinal diseases
      during the same period in each hospital. METHODS: Fifty-seven patients with low
      back pain who had a one-level posterior lumbar interbody fusion using a newly
      designed expandable cage were enrolled in this study at five centers from June
      2003 to December 2004 and followed up for 24 months. Pain improvement was checked
      with a Visual Analogue Scale (VAS) and their disability was evaluated with the
      Oswestry Disability Index. Radiographs were obtained before and after surgery. At
      the final follow-up, dynamic stability, quality of bone fusion, interveretebral
      disc height, and lumbar lordosis were assessed. In some cases, a lumbar computed
      tomography scan was also obtained. RESULTS: The mean VAS score of back pain was
      improved from 6.44 points preoperatively to 0.44 at the final visit and the score
      of sciatica was reduced from 4.84 to 0.26. Also, the Oswestry Disability Index
      was improved from 32.62 points preoperatively to 18.25 at the final visit. The
      fusion rate was 92.5%. Intervertebral disc height, recorded as 9.94+/-2.69 mm
      before surgery was increased to 12.23+/-3.31 mm at postoperative 1 month and was
      stabilized at 11.43+/-2.23 mm on final visit. The segmental angle of lordosis was
      changed significantly from 3.54+/-3.70 degrees before surgery to 6.37+/-3.97
      degrees by 24 months postoperative, and total lumbar lordosis was 20.37+/-11.30
      degrees preoperatively and 24.71+/-11.70 degrees at 24 months postoperative.
      CONCLUSION: There have been no special complications regarding the expandable
      cage during the follow-up period and the results of this study demonstrates a
      high fusion rate and clinical success.

PMID- 19096553
TI  - The incidence of aneurysmal subarachnoid hemorrhage in youngdong district, Korea.
AB  - OBJECTIVE: The purpose of this study is to investigate the incidence of
      aneurysmal subarachnoid hemorrhage (SAH) in Youngdong district for 10 years.
      METHODS: From Jan. 1997 to Dec. 2006, 732 patients (327 males, 405 females, mean
      age: 54.8+/-13.1 years) with spontaneous SAH were admitted to our hospital. We
      reviewed the medical records and radiological findings regarding to the ictus of
      SAH, location and size of the ruptured aneurysms, Hunt-Hess grade and Fisher
      grade on admission, personal details such as address, age, and sex, and previous
      history of medical diseases. RESULTS: In these 732 patients, 672 cases were
      confirmed as aneurysmal SAH. Among them, 611 patients (262 males, 349 females,
      mean age: 54.9+/-13.2 years) came from Youngdong district. The average crude
      annual incidence of aneurysmal SAH for men, women, and both sexes combined in
      Youngdong district was 7.8+/-1.7, 10.5+/-2.7, and 9.1+/-2.1 per 100,000
      population, respectively. Because of the problems related to the observation
      period and geographical confinement, it was suspected that the representative
      incidence of aneurysmal SAH in Youngdong district should be made during the later
      eight years in six coastal regions. Therefore, the average age-adjusted annual
      incidence for men, women, and both sexes combined was 8.8+/-1.4, 11.2+/-1.3 and
      10.0+/-1.0, respectively in the coastal regions of Youngdong district from 1999
      to 2006. CONCLUSION: In overall, our results on the incidence of aneurysmal SAH
      was not very different from previous observations from other studies.

PMID- 19096555
TI  - Outcome and efficacy of height gain and sagittal alignment after kyphoplasty of
      osteoporotic vertebral compression fractures.
AB  - OBJECTIVE: Although a significant correction of local kyphosis has been reported
      previously, only a few studies have investigated whether this correction leads to
      an improved overall sagittal alignment. The study objective was to determine
      whether an improvement in the local kyphotic angle improves the overall sagittal
      alignment. We examined and compared the effects of thoracic and lumbar level
      kyphoplasty procedures on local versus overall sagittal alignment of the spine.
      METHODS: Thirty-eight patients with osteoporotic vertebral compression fractures
      who showed poor response to conventional, palliative medical therapy underwent
      single-level kyphoplasty. The pertinent clinical data of these patients, from
      June 2006 to November 2006, were reviewed retrospectively. We measured
      preoperative and postoperative vertebral body heights, which were classified as
      anterior, middle, or posterior fractured vertebral body heights. Furthermore, the
      local and overall sagittal angles after polymethylmethacrylate deposition were
      measured. RESULTS: More height was gained at the thoracic level, and the middle
      vertebral height regained the most. A significant local kyphosis correction was
      observed at the fractured level, and the correction at larger spanning segments
      decreased with the distance from the fractured level. CONCLUSION: The inflatable
      balloon kyphoplasty procedure was the most effective in regaining the height of
      the thoracic fractured vertebra in the middle vertebral body. The kyphosis
      correction by kyphoplasty was mainly achieved in the fractured vertebral body.
      Sagittal angular correction decreased with an increase in the distance from the
      fractured vertebra. No significant improvement was observed in the overall
      sagittal alignment after kyphoplasty. Further studies in a larger population are
      required to clarify this issue.

PMID- 19096554
TI  - Short-segment Pedicle Instrumentation of Thoracolumbar Burst-compression
      Fractures; Short Term Follow-up Results.
AB  - OBJECTIVE: The current literature implies that the use of short-segment pedicle
      screw fixation for spinal fractures is dangerous and inappropriate because of its
      high failure rate, but favorable results have been reported. The purpose of this
      study is to report the short term results of thoracolumbar burst and compression
      fractures treated with short-segment pedicle instrumentation. METHODS: A
      retrospective review of all surgically managed thoracolumbar fractures during six
      years were performed. The 19 surgically managed patients were instrumented by the
      short-segment technique. Patients' charts, operation notes, preoperative and
      postoperative radiographs (sagittal index, sagittal plane kyphosis, anterior body
      compression, vertebral kyphosis, regional kyphosis), computed tomography scans,
      neurological findings (Frankel functional classification), and follow-up records
      up to 12-month follow-up were reviewed. RESULTS: No patients showed an increase
      in neurological deficit. A statistically significant difference existed between
      the patients preoperative, postoperative and follow-up sagittal index, sagittal
      plane kyphosis, anterior body compression, vertebral kyphosis and regional
      kyphosis. One screw pullout resulted in kyphotic angulation, one screw was
      misplaced and one patient suffered angulation of the proximal segment on follow
      up, but these findings were not related to the radiographic findings. Significant
      bending of screws or hardware breakage were not encountered. CONCLUSION: Although
      long term follow-up evaluation needs to verified, the short term follow-up
      results suggest a favorable outcome for short-segment instrumentation. When
      applied to patients with isolated spinal fractures who were cooperative with 3-4
      months of spinal bracing, short-segment pedicle screw fixation using the
      posterior approach seems to provide satisfactory result.

PMID- 19096556
TI  - Falx meningiomas: surgical results and lessons learned from 68 cases.
AB  - OBJECTIVE: The purpose of this study was to review the characteristics of falcine
      meningioma retrospectively and to identify the parameters associated with tumor
      recurrence. METHODS: The analysis included; age, sex, extent of resection, and
      radiologic and pathologic findings. Falcine meningiomas were classified by
      location as anterior, middle, or posterior as described for parasagittal
      meningiomas. RESULTS: Of the 795 meningioma patients treated between 1990 and
      2004 at the authors' institution, 68 patients with meningiomas arising from the
      falx underwent craniotomies. There were 22 male and 46 female patients (1 : 2.1).
      Mean age was 55 years and ranged from 14 to 77 years. Locations of falcine
      meningioma were; the anterior third in 33 cases, middle in 20, and posterior in
      15. Mean tumor volume was 42 cc and ranged from 4 to 140 cc. In 58 of the 68
      patients tumors were totally removed. Additional surgery for recurrence was
      performed in 6 patients over 15 years. Of these 6 patients, only two patients
      underwent gross total tumor resection at first operation; the other four
      underwent subtotal tumor resection. Based on pathologic reports, the largest
      tumor subtype was transitional. There were four patients with a high grade tumor
      three atypical and one anaplastic meningioma. Of the 68 patients, 59 achieved a
      good outcome (no neurological deficit or recurrence), six had temporary
      complications, two suffered new permanent postoperative deficits, and the
      remaining one died due to severe brain swelling despite postoperative intensive
      care. Extent of surgical resection was found to be significantly related to tumor
      recurrence. CONCLUSION: Falcine meningioma accounted for 8.5% of intracranial
      meningiomas and the transitional meningioma was the most common subtype of
      falcine meningioma. Gross total resection of tumor was the single most important
      predictor of an improved surgical outcome.

PMID- 19096557
TI  - Surgical experience of the ruptured distal anterior cerebral artery aneurysms.
AB  - OBJECTIVE: Distal anterior cerebral artery (DACA) aneurysms are fragile and known
      to have high risks for intraoperative premature rupture and a relatively high
      associated morbidity. To improve surgical outcomes of DACA aneurysms, we reviewed
      our surgical strategy and its results postoperatively. METHODS: A total of 845
      patients with ruptured cerebral aneurysms were operated in our hospital from
      January 1991 to December 2005. Twenty-three of 845 patients had ruptured DACA
      aneurysms which were operated on according to our surgical strategy. Our surgical
      strategy was as follows; early surgery, appropriate releasing of CSF, appropriate
      surgical approach, using neuronavigating system, securing the bridging veins,
      using temporary clipping and/or tentative clipping, meticulous manipulation of
      aneurysm, and using micro-Doppler flow probe. Twenty of 23 patients who had
      complete medical records were studied retrospectively. We observed the
      postoperative radiographic findings and checked Glasgow Outcome Scale score sixth
      months after the operation. RESULTS: Nineteen DACA aneurysms were clipped through
      a unilateral interhemispheric approach and one DACA aneurysm was clipped through
      a pterional approach. Postoperative radiographic findings revealed complete
      clipping of aneurysmal neck without stenosis or occlusion of parent arteries. In
      two patients, a residual neck of aneurysm was visualized. Seventeen patients
      showed good recovery, one patient resulted in moderate disability, while 2
      patients died. CONCLUSION: With our surgical strategy it was possible to achieve
      acceptable surgical morbidity and mortality rates in patients with DACA
      aneurysms. Appropriate use of tentative clipping, temporary clipping and neuro
      navigating systems can give great help for safe approach and clipping of DACA
      aneurysm.

PMID- 19096558
TI  - Long-term Outcomes of Gamma Knife Stereotactic Radiosurgery of Vestibular
      Schwannomas.
AB  - OBJECTIVE: Gamma Knife Stereotactic Radiosurgery (GK SRS) has become an important
      treatment modality for vestibular schwannomas. We evaluated the tumor control
      rate, patterns of tumor volume change and preservation of hearing following low
      dose radiation for vestibular schwannomas in a homogeneous cohort group in which
      the mean marginal dose was 12 Gy. METHODS: A total of 59 patients were enrolled
      in this study. All enrolled patients were followed-up for at least 5 years and
      the radiation dose was 11-13 Gy. Regular MRI, audiometry and clinical evaluations
      were done and tumor volumes were obtained from MRI using the OSIRIS program.
      RESULTS: The tumor control rate was 97%. We were able to classify the patterns of
      change in tumor volume into three categories. Transient increases in tumor volume
      were detected in 29% of the patients and the maximum transient increase in tumor
      volume was identified at 6 to 30 months after GK SRS. The transient increases in
      tumor volume ranged from 121% to 188%. Hearing was preserved in 4 of the 12
      patients who had serviceable hearing prior to treatment. There were no other
      complications associated with GK SRS. CONCLUSION: Low-dose GK SRS was an
      effective and safe mode of treatment for vestibular schwannomas in comparison to
      the previously used high-dose GK SRS. Transient increases in tumor volume can be
      identified during the follow-up period after low-dose GK SRS for vestibular
      schwannomas. Physicians should be aware that these increases are not always
      indicative of treatment failure and that close observation is required following
      treatments. Unfortunately, a satisfactory hearing preservation rate was not
      achieved by reducing the radiation dose. It is thought that hearing preservation
      is a more sophisticated problem and further research is required.

PMID- 19096559
TI  - Clinical Analysis of Video-assisted Thoracoscopic Spinal Surgery in the Thoracic
      or Thoracolumbar Spinal Pathologies.
AB  - OBJECTIVE: Thoracoscopic spinal surgery provides minimally invasive approaches
      for effective vertebral decompression and reconstruction of the thoracic and
      thoracolumbar spine, while surgery related morbidity can be significantly
      lowered. This study analyzes clinical results of thoracoscopic spinal surgery
      performed at our institute. METHODS: Twenty consecutive patients underwent video
      assisted thoracosopic surgery (VATS) to treat various thoracic and thoracolumbar
      pathologies from April 2000 to July 2006. The lesions consisted of spinal trauma
      (13 cases), thoracic disc herniation (4 cases), tuberculous spondylitis (1 case),
      post-operative thoracolumbar kyphosis (1 case) and thoracic tumor (1 case). The
      level of operation included upper thoracic lesions (3 cases), midthoracic lesions
      (6 cases) and thoracolumbar lesions (11 cases). We classified the procedure into
      three groups: stand-alone thoracoscopic discectomy (3 cases), thoracoscopic
      fusion (11 cases) and video assisted mini-thoracotomy (6 cases). RESULTS:
      Analysis on the Frankel performance scale in spinal trauma patients (13 cases),
      showed a total of 7 patients who had neurological impairment preoperatively :
      Grade D (2 cases), Grade C (2 cases), Grade B (1 case), and Grade A (2 cases).
      Four patients were neurologically improved postoperatively, two patients were
      improved from C to E, one improved from grade D to E and one improved from grade
      B to grade D. The preoperative Cobb's and kyphotic angle were measured in spinal
      trauma patients and were 18.9+/-4.4 degrees and 18.8+/-4.6 degrees ,
      respectively. Postoperatively, the angles showed statistically significant
      improvement, 15.1+/-3.7 degrees and 11.3+/-2.4 degrees , respectively (P<0.001).
      CONCLUSION: Although VATS requires a steep learning curve, it is an effective and
      minimally invasive procedure which provides biomechanical stability in terms of
      anterior column decompression and reconstruction for anterior load bearing, and
      preservation of intercostal muscles and diaphragm.

PMID- 19096560
TI  - Surgical outcome of spinal canal meningiomas.
AB  - OBJECTIVE: We report experiences and clinical outcomes of 61 cases with spinal
      canal meningiomas from January 1970 through January 2005. METHODS: Thirty-eight
      patients were enrolled with follow-up duration of more than one year after
      surgery. There were 7 male and 31 female patients. The mean age was 52 years
      (range, 19 to 80 years). All patients underwent microsurgical resection using a
      posterior approach. RESULTS: Twenty-nine (79.4%) cases experienced clinical
      improvement after surgery. The extent of tumor resection at the first operation
      was Simpson Grade I in 10 patients, Grade II in 17, Grade III in 4, Grade IV in
      6, and unknown in one. We did not experience recurrent cases with Simpson grade
      I, II, or III resection. There were 6 recurrent cases, consisting of 5 cases with
      an extent of Simpson grade IV and one with an unknown extent. The mean duration
      of recurrence was 100 months after surgery. Radiation therapy was administered as
      a surgical adjunct in four patients (10.5%). Two cases were recurrent lesions
      that could not be completely resected. The other two cases were malignant
      meningiomas. No immediate postoperative death occurred in the patient group.
      CONCLUSION: We experienced no recurrent cases of intraspinal meningiomas once
      gross total resection has been achieved, regardless of the control of the dural
      origin. Surgeons do not have to take the risk of causing complication to the
      control dural origin after achieving gross total resectioning of spinal canal
      meningioma.

PMID- 19096561
TI  - The management of bilateral interfacetal dislocation with anterior fixation in
      cervical spine : comparison with combined antero-posterior fixation.
AB  - OBJECTIVE: Combined antero-posterior fixation has been a standard method for
      bilateral interfacetal dislocation in cervical spine. The purpose of this study
      is to evaluate the efficacy and complication of anterior cervical stabilization
      in treatment of bilateral interfacetal dislocation. METHODS: A total of 65 cases
      of traumatic bilateral interfacetal dislocation in cervical spine who were
      managed in our institution, from Mar. 1997 to Feb. 2006, were included in this
      study. Closed reduction was tried in all cases before operation. If closed
      reduction was accomplished successfully, only anterior cervical fixation was
      performed (Group I), and attempted to place screws bicortically as possible with
      unicortical screws. If failed, posterior open reduction with fixation was first
      tried, followed by anterior cervical fixation (Group II). All patients were
      evaluated for neurological outcome and radiological evidence of healing. RESULTS:
      The Group I included 47 patients and the Group II, 18 patients. The improvement
      of Frankel grade and increase of mean cervical lordosis angles were not
      statistically different between two groups. Screw-plate system used did not
      influence the outcome. On follow up, solid bone fusion was evident and there were
      no cases of instability in both groups. CONCLUSION: Our study demonstrated that
      anterior cervical fixation on BID is safe and effective in comparison with
      combined antero-posterior cervical fixation.

PMID- 19096562
TI  - Clinical experiences and usefulness of cervical posterior stabilization with
      polyaxial screw-rod system.
AB  - OBJECTIVE: The objective of this study is to investigate the safety, surgical
      efficacy, and advantages of a polyaxial screw-rod system for posterior
      occipitocervicothoracic arthrodesis. METHODS: Charts and radiographs of 32
      patients who underwent posterior cervical fixation between October 2004 and
      February 2006 were retrospectively reviewed. Posterior cervical polyaxial screw
      rod fixation was applied on the cervical spine and/or upper thoracic spine. The
      surgical indication was fracture or dislocation in 18, C1-2 ligamentous injury
      with trauma in 5, atlantoaxial instability by rheumatoid arthritis (RA) or
      diffuse idiopathic skeletal hyperostosis (DISH) in 4, cervical spondylosis with
      myelopathy in 4, and spinal metastatic tumor in 1. The patients were followed up
      and evaluated based on their clinical status and radiographs at 1, 3, 6 months
      and 1 year after surgery. RESULTS: A total of 189 screws were implanted in 32
      patients. Fixation was carried out over an average of 3.3 spinal segment (range,
      2 to 7). The mean follow-up interval was 20.2 months. This system allowed for
      screw placement in the occiput, C1 lateral mass, C2 pars, C3-7 lateral masses, as
      well as the lower cervical and upper thoracic pedicles. Satisfactory bony fusion
      and reduction were achieved and confirmed in postoperative flexion-extension
      lateral radiographs and computed tomography (CT) scans in all cases. Revision
      surgery was required in two cases due to deep wound infection. One case needed a
      skin graft due to necrotic change. There was one case of kyphotic change due to
      adjacent segmental degeneration. There were no other complications, such as cord
      or vertebral artery injury, cerebrospinal fluid leak, screw malposition or back
      out, or implant failure, and there were no cases of postoperative radiculopathy
      due to foraminal stenosis. CONCLUSION: Posterior cervical stabilization with a
      polyaxial screw-rod system is a safe and reliable technique that appears to offer
      several advantages over existing methods. Further biomechanical testings and
      clinical experiences are needed in order to determine the true benefits of this
      procedure.

PMID- 19096563
TI  - A clinical analysis of surgical treatment for spontaneous spinal infection.
AB  - OBJECTIVE: The purpose of the study was to determine the clinical effects of
      anterior radical debridement on a series of patients with spontaneous spinal
      infection. METHODS: We retrospectively analyzed the clinical characteristics of
      32 patients who underwent surgical treatment from January 2000 to December 2005
      in our department. The average follow-up Period was 33.4 months (range, 6 to 87
      months). Thirty-two patients presented with the following : 23 cases with
      pyogenic spondylitis, eight with tuberculous spondylitis and one with fungal
      spondylitis. The indications for surgery were intractable pain, failure of
      medical management, neurological impairment with or without an associated
      abscess, vertebral destruction causing spinal instability and/or segmental
      kyphosis. RESULTS: The study included 15 (46.9%) males and 17 (53.1%) females
      ranging in age from 26 to 75 years (mean, 53.1 years). Diabetes mellitus (DM) and
      pulmonary Tbc were the most common predisposing factors for pyogenic spondylitis
      and tuberculous spondylitis. Staphylococcus aureus (13%) was the main organism
      isolated. The most prevalent location was the lumbar spine (75%). Changes in the
      pain score, Frankel's classification, and laboratory parameters demonstrated a
      significant clinical improvement in all patients. However, there were recurrent
      infections in two patients with tuberculous spondylitis and inappropriate
      debridement and intolerance of medication and noncompliance. Autologous rib,
      iliac bone and allograft (fibular) were performed in most patients. However, 10
      patients were grafted using a titanium mesh cage after anterior radical
      debridement. There were no recurrent infections in the 10 cases using the mesh
      cage with radical debridement. CONCLUSION: The findings of this study indicate
      that surgery based on appropriate surgical indications is effective for the
      control of spinal infection and prevention of recurrence with anterior radical
      debridement, proper drug use and abscess drainage.

PMID- 19096564
TI  - Surgical treatment for acute, severe brain infarction.
AB  - OBJECTIVE: Stroke is the most prevalent disease involving the central nervous
      system. Since medical modalities are sometimes ineffective for the acute edema
      following massive infarction, surgical decompression may be an effective option
      when medical treatments fail. The present study was undertaken to assess the
      outcome and prognostic factors of decompressive surgery in life threatening
      acute, severe, brain infarction. METHODS: We retrospectively analyzed twenty-six
      patients (17 males and 9 females; average age, 49.7yrs) who underwent
      decompressive surgery for severe cerebral or cerebellar infarction from January
      2003 to December 2006. Surgical indication was based on the clinical signs such
      as neurological deterioration, pupillary reflex, and radiological findings.
      Clinical outcome was assessed by Glasgow Outcome Scale (GOS). RESULTS: Of the 26
      patients, 5 (19.2%) showed good recovery, 5 (19.2%) showed moderate disability, 2
      (7.7%) severe disability, 6 (23.1%) persistent experienced vegetative state, and
      8 (30.8%) death. In this study, the surgical decompression improved outcome for
      cerebellar infarction, but decompressive surgery did not show a good result for
      MCA infarction (30.8% overall mortality vs 100% mortality). The dominant
      hemisphere infarcts showed worse prognosis, compared with nondominant-hemisphere
      infarcts (54.5% vs 70%). Poor prognostic factors were diabetes mellitus, dominant
      hemisphere infarcts and low preoperative Glasgow Coma Scale (GCS) score.
      CONCLUSION: The patients who exhibit clinical deterioration despite aggressive
      medical management following severe cerebral infarction should be considered for
      decompressive surgery. For better outcome, prompt surgical treatment is
      mandatory. We recommend that patients with severe cerebral infarction should be
      referred to neurosurgical department primarily in emergency setting or as early
      as possible for such prompt surgical treatment.

PMID- 19096565
TI  - Surgical management of massive cerebral infarction.
AB  - OBJECTIVE: The aim of this study was to analyze the treatment results and
      prognostic factors in patients with massive cerebral infarction who underwent
      decompressive craniectomy. METHODS: From January 2000 to December 2005, we
      performed decompressive craniectomy in 24 patients with massive cerebral
      infarction. We retrospectively reviewed the medical records, radiological
      findings, initial clinical assessment using the Glasgow Coma Scale, serial
      computerized tomography (CT) with measurement of midline and septum pellucidum
      shift, and cerebral infarction territories. Patients were evaluated based on the
      following factors : the pre- and post-operative midline shifting on CT scan,
      infarction area or its dominancy, consciousness level, pupillary light reflex and
      Glasgow Outcome Scale. RESULTS: All 24 patients (11 men, 13 women; mean age, 63
      years; right middle cerebral artery (MCA) territory, 17 patients; left MCA
      territory, 7 patients) were treated with large decompressive craniectomy and
      duroplasty. The average time interval between the onset of symptoms and surgical
      decompression was 2.5 days. The mean Glasgow Coma Scale was 12.4 on admission and
      8.3 preoperatively. Of the 24 surgically treated patients, the good outcome group
      (Group 2 : GOS 4-5) comprised 9 cases and the poor outcome group (Group1 : GOS 1
      3) comprised 15 cases. CONCLUSION: We consider decompressive craniectomy for
      large hemispheric infarction as a life-saving procedure. Good preoperative GCS,
      late clinical deterioration, small size of the infarction area, absence of
      anisocoria, and preoperative midline shift less than 11mm were considered to be
      positive predictors of good outcome. Careful patient selection based on the above
      mentioned factors and early operation may improve the functional outcome of
      surgical management for large hemispheric infarction.

PMID- 19096566
TI  - Accumulated mannitol and aggravated cerebral edema in a rat model of middle
      cerebral artery infarction.
AB  - OBJECTIVE: Repeated administration of mannitol in the setting of large
      hemispheric infarction is a controversial and poorly defined therapeutic
      intervention. This study was performed to examine the effects of multiple-dose
      mannitol on a brain edema after large hemispheric infarction. METHODS: A middle
      cerebral artery was occluded with the rat suture model for 6 hours and reperfused
      in 22 rats. The rats were randomly assigned to either control (n=10) or the
      mannitol-treated group (n=12) in which intravenous mannitol infusions (0.8 g/kg)
      were performed six times every four hours. After staining a brain slice with
      2,3,5-triphenyltetrazolium chloride, the weight of hemispheres, infarcted (IH)
      and contralateral (CH), and the IH/CH weight ratio were examined, and then
      hemispheric accumulation of mannitol was photometrically evaluated based on
      formation of NADH catalyzed by mannitol dehydrogenase. RESULTS: Mannitol
      administration produced changes in body weight of -7.6+/-1.1%, increased plasma
      osmolality to 312+/-8 mOsm/L. It remarkably increased weight of IH (0.77+/-0.06
      gm versus 0.68+/-0.03 gm : p<0.01) and the IH/CH weight ratio (1.23+/-0.07 versus
      1.12+/-0.05 : p<0.01). The photometric absorption at 340 nm of the cerebral
      tissue in the mannitol-treated group was increased to 0.375+/-0.071 and 0.239+/
      0.051 in the IH and CH, respectively from 0.167+/-0.082 and 0.162+/-0.091 in the
      IH and CH of the control group (p<0.01). CONCLUSION: Multiple-dose mannitol is
      likely to aggravate cerebral edema due to parenchymal accumulation of mannitol in
      the infarcted brain tissue.

PMID- 19096567
TI  - Saccular aneurysm of the azygos anterior cerebral artery: three case reports.
AB  - The azygos anterior cerebral artery, a rare anomaly in the circle of Willis in
      which only a single vessel supplies the medial aspects of both anterior cerebral
      hemispheres, is closely associated with saccular aneurysms. We present three
      cases of azygos anterior cerebral artery aneurysms among the 781 cerebral
      aneurysms surgically treated at our institution in an 11-year period. These three
      cases all involved elderly women who presented with subarachnoid hemorrhage.
      Conventional cerebral angiography and CT angiography revealed small saccular
      aneurysms at the distal ends of the azygos anterior cerebral arteries. These
      aneurysms were clipped successfully using a bifrontal interhemispheric approach.
      Hence, the pathogenesis of these particular aneurysms relating to hemodynamic
      change, associated anomalies, and surgical pitfalls is discussed with review of
      literature.

PMID- 19096568
TI  - Elevation of depressed skull fracture with a cup of breast pump and a suction
      generator : a case report in technical aspects.
AB  - Surgical elevation of the depressed bone is known to be the conventional
      treatment usually recommended for a simple depressed skull fracture in the adult
      or pediatric age. The authors introduce, however, a case of depressed skull
      fracture in an infant which was elevated by means of a cup of breast pump and a
      suction generator without surgical elevation. In our case, without surgery, a
      'cup-shaped' depressed skull fracture in an infant was safely elevated with no
      neurological signs. This method is considered a simple, effective, safe, and
      alternative procedure in an infant with simple depressed skull fracture.

PMID- 19096569
TI  - Hemifacial spasm: a neurosurgical perspective.
AB  - Hemifacial spasm (HFS) is characterized by tonic clonic contractions of the
      muscles innervated by the ipsilateral facial nerve. Compression of the facial
      nerve by an ectatic vessel is widely recognized as the most common underlying
      etiology. HFS needs to be differentiated from other causes of facial spasms, such
      as facial tic, ocular myokymia, and blepharospasm. To understand the overall
      craniofacial abnormalities and to perform the optimal surgical procedures for
      HFS, we are to review the prevalence, pathophysiology, differential diagnosis,
      details of each treatment modality, usefulness of brainstem auditory evoked
      potentials monitoring, debates on the facial EMG, clinical course, and
      complications from the literature published from 1995 to the present time.

PMID- 19096570
TI  - Balloon Kyphoplasty through Extrapedicular Approach in the Treatment of Middle
      Thoracic Osteoporotic Compression Fracture : T5-T8 Level.
AB  - OBJECTIVE: Kyphoplasty performed in the middle thoracic spine presents technical
      challenges that differ from those in the lower thoracic or lumbar region due to
      small pedicle size and angular severity for thoracic kyphosis. The purpose of
      this study was to evaluate the efficacy of balloon kyphoplasty through
      extrapedicular approach for the treatment of intractable osteoporotic compression
      fractures in the middle thoracic spine. METHODS: The patients who were performed
      with one level balloon kyphoplasty through extrapedicular approach due to painful
      osteoporotic compression fractures at T5-T8 from June 2003 to July 2005 were
      retrospectively analyzed. Imaging and clinical features were analyzed including
      involved vertebrae level, vertebral height, injected cement volume, clinical
      outcome and complications. RESULTS: Eighteen female patients (age ranged from 60
      to 77 years old) were included in this study. The average amount of the implanted
      cement was 4.2+/-1.5 cc. The mean cobb angle and compression rate were improved
      from 12.1+/-6.5 degrees to 8.5+/-7.2 degrees and from 30% to 15%, respectively.
      The mean pain score (visual analogue scale) prior to kyphoplasty was 7.9 and it
      decreased to 3.0 after the procedure. Cement leakage to the adjacent disc (2
      cases) and paravertebral soft tissues (1 case) were seen but there were no major
      complications such as pneumothorax, segmental artery injury, pulmonary embolism,
      or epidural leakage. CONCLUSION: Balloon kyphoplasty through extrapedicular
      approach is considered as a safe and effective in treating the middle thoracic
      regions with low complication rate.

PMID- 19096571
TI  - Subsidence of Cylindrical Cage (AMSLUtrade mark Cage) : Postoperative 1 Year
      Follow-up of the Cervical Anterior Interbody Fusion.
AB  - OBJECTIVE: There are numerous reports on the primary stabilizing effects of the
      different cervical cages for cervical radiculopathy. But, little is known about
      the subsidence which may be clinical problem postoperatively. The goal of this
      study is to evaluate subsidence of cage and investigate the correlation between
      radiologic subsidence and clinical outcome. METHODS: To assess possible
      subsidence, the authors investigated clinical and radiological results of the one
      hundred patients who underwent anterior cervical fusion by using AMSLUtrade mark
      cage during the period between January 2003 and June 2005. Preoperative and
      postoperative lateral radiographs were measured for height of intervertebral disc
      space where cages were placed. Intervertebral disc space was measured by dividing
      the sum of anterior, posterior, and midpoint interbody distance by 3. Follow-up
      time was 6 to 12 months. Subsidence was defined as any change in at least one of
      our parameters of at least 3 mm. RESULTS: Subsidence was found in 22 patients
      (22%). The mean value of subsidence was 2.21 mm, and mean subsidence rate was
      22%. There were no cases of the clinical status deterioration during the follow
      up period. No posterior or anterior migration was observed. CONCLUSION: The
      phenomenon of subsidence is seen in substantial number of patients. Nevertheless,
      clinical and radiological results of the surgery were favorable. An excessive
      subsidence may result in hardware failure. Endplate preservation may enables us
      to control subsidence and reduce the number of complications.

PMID- 19096572
TI  - Segmental deformity correction after balloon kyphoplasty in the osteoporotic
      vertebral compression fracture.
AB  - OBJECTIVE: Balloon kyphoplasty can effectively relieve the symptomatic pain and
      correct the segmental deformity of osteoporotic vertebral compression fractures.
      While many articles have reported on the effectiveness of the procedure, there
      has not been any research on the factors affecting the deformity correction.
      Here, we evaluated both the relationship between postoperative pain relief and
      restoration of the vertebral height, and segmental kyphosis, as well as the
      various factors affecting segmental deformity correction after balloon
      kyphoplasty. METHODS: Between January 2004 and December 2006, 137 patients (158
      vertebral levels) underwent balloon kyphoplasty. We analyzed various factors such
      as the age and sex of the patient, preoperative compression ratio, kyphotic angle
      of compressed segment, injected PMMA volume, configuration of compression,
      preoperative bone mineral density (BMD) score, time interval between onset of
      symptom and the procedure, visual analogue scale (VAS) score for pain rating and
      surgery-related complications. RESULTS: The mean postoperative VAS score
      improvement was 4.93+/-0.17. The mean postoperative height restoration rate was
      17.8+/-1.57% and the kyphotic angle reduction was 1.94+/-0.38 degrees . However,
      there were no significant statistical correlations among VAS score improvement,
      height restoration rate, and kyphotic angle reduction. Among the various factors,
      the configuration of the compressed vertebral body (p=0.002) was related to the
      height restoration rate and the direction of the compression (p=0.006) was
      related with the kyphotic angle reduction. The preoperative compression ratio
      (p=0.023, p=0.006) and injected PMMA volume (p<0.001, p=0.035) affected both the
      height restoration and kyphotic angle reduction. Only the preoperative
      compression ratio was found to be as an independent affecting factor (95% CI :
      1.064-5.068). CONCLUSION: The two major benefits of balloon kyphoplasty are
      immediate pain relief and local deformity correction, but segmental deformity
      correction achieved by balloon kyphoplasty does not result in additional pain
      relief. Among the factors that were shown to affect the segmental deformity
      correction, configuration of the compressed vertebral body, direction of the most
      compressed area, and preoperative compression ratio were not modifiable. However,
      careful preoperative consideration about the modifiable factor, the PMMA volume
      to inject, may contribute to the dynamic correction of the segmental deformity.

PMID- 19096573
TI  - A Comparative Coagulopathic Study for Treatment of Vasospasm by Using Low- and
      High-molecular Weight Hydroxyethyl Starches.
AB  - OBJECTIVE: High-molecular-weight hydroxyethyl starch (HES) compromises blood
      coagulation more than does low-molecular-weight HES. We compared the effects of
      low- and high-molecular-weight HES for the treatment of vasospasm and
      investigated the dose relationship with each other. METHODS: Retrospectively, in
      a series of consecutive 102 patients with subarachnoid hemorrhage (SAH), 35
      patients developed clinical symptoms of vasospasm of these fourteen patients were
      treated with low-molecular-weight HES for volume expansion while the other 21
      received high-molecular-weight HES as continuous intravenous infusion.
      Prothrombin time (PT), partial thromboplastin time (PTT), fibrinogen level, and
      platelet count were all measured prior to initiation, during treatment and after
      termination of therapy for symptomatic vasospasm. The total dose of HES ranged
      from 5 L to 14 L and median infusion duration was 10 days. RESULTS: A more
      pronounced PTT prolongation was observed in high-molecular-weight HES group
      compared with low-molecular-weight HES group. No other coagulation parameters
      were altered. Dosage (=duration) shows a positive correlation with PTT.
      Clinically, significant bleeding episodes were noted in four patients who
      received high-molecular-weight HES. CONCLUSION: Coagulopathy was developed in
      direct proportion to molecular weight of starch and dosages. We propose the
      extreme caution in the administration of HES solution for the vasospasm
      treatment.

PMID- 19096574
TI  - Simple decompression of the ulnar nerve for cubital tunnel syndrome.
AB  - OBJECTIVE: Cubital tunnel syndrome is the second most common entrapment
      neuropathy of the upper extremity. Although many different operative techniques
      have been introduced, none of them have been proven superior to others. Simple
      cubital tunnel decompression has numerous advantages, including simplicity and
      safety. We present our experience of treating cubital tunnel syndrome with simple
      decompression in 15 patients. METHODS: According to Dellon's criteria, one
      patient was classified as grade 1, eight as grade 2, and six as grade 3.
      Preoperative electrodiagnostic studies were performed in all patients and 7 of
      them were rechecked postoperatively. Five patients of 15 underwent simple
      decompression using a small skin incision (2 cm or less). RESULTS: Preoperative
      mean value of motor conduction velocity (MCV) within the segment (above the elbow
      below the elbow) was 41.8+/-15.2 m/s and this result showed a decrease compared
      to the result of MCV in the below the elbow-wrist segment (57.8+/-6.9 m/s) with
      statistical significance (p<0.05). Postoperative mean values of MCV were improved
      in 6 of 7 patients from 39.8+/-12.1 m/s to 47.8+/-12.1 m/s (p<0.05). After an
      average follow-up of 4.8+/-5.3 months, 14 patients of 15 (93%) reported good or
      excellent clinical outcomes according to a modified Bishop scoring system. Five
      patients who had been treated using a small skin incision achieved good or
      excellent outcomes. There were no complications, recurrences, or subluxation of
      the ulnar nerve. CONCLUSION: Simple decompression of the ulnar nerve is an
      effective and successful minimally invasive technique for patients with cubital
      tunnel syndrome.

PMID- 19096575
TI  - Clipping of the Anterior Communicating Artery Aneurysm without Sylvian Fissure
      Dissection.
AB  - OBJECTIVE: The focus of aneurysm surgery is eliminating unnecessary operative
      manipulations and preparing the surgeon for any crises that might arise. With
      this concept in mind, we have tried resection of the gyrus rectus without routine
      sylvian fissure dissection in selected patients with anterior communicating
      artery (ACom) aneurysms, and compared these results with those from the
      conventional transsylvian approach. METHODS: This retrospective study included
      231 surgically treated patients with ACom aneurysms from March, 1997 to May,
      2005. The patients were divided into two groups : Group A (96 with sylvian
      fissure dissection, March, 1997-December, 2000) and Group B (135 without sylvian
      fissure dissection, January, 2001-May, 2005). Overall surgical outcomes were
      compared, and operative times have been prospectively recorded since January, 04
      to evaluate how this maneuver affected the length of surgical procedures.
      RESULTS: All aneurysms were satisfactorily clipped, and there was no evidence of
      increased number of procedure-related retraction injuries in group B. Overall
      outcome was good in 186 (80.5%); 76 (79.2%) in group A, and 110 (81.5%) in group
      B (x(2) test, p=0.79). In good clinical grade of group A, good outcome was
      observed in 60 patients (89.6%) and in group B, 97 patients (94.2%) (Fisher's
      exact test, p=0.38) (Fig. 2). CONCLUSION: In this study, eliminating the step of
      sylvian fissure dissection by gentle lateral basal-frontal retraction to the side
      of the sylvian fissure did not increase morbidity and mortality. However, we do
      not intend to modify the standard approach to the ACom aneurysm that is familiar
      to and has been mastered by many others. Rather, we report our experience on the
      basis of our anatomic understanding of the technique and its results.

PMID- 19096576
TI  - Enhancement of Arsenic Trioxide (As(2)O(3))- Mediated Apoptosis Using Berberine
      in Human Neuroblastoma SH-SY5Y Cells.
AB  - OBJECTIVE: Arsenic trioxide (As(2)O(3)) has been used as an anticancer agent in
      traditional Chinese medicine for thousand years and berberine is an isoquinoline
      alkaloid present that has indicated significant antimicrobial activity. We have
      examined the combined anticancer effects of As(2)O(3) and berberine against the
      human neuroblastoma (HNB) SH-SY5Y cells in vitro, and to elucidate underlying
      molecular mechanism. METHODS: HNB SH-SY5Y cells were treated with 2 microM
      As(2)O(3) and 75 microg/ml berberine, and their survival, cell death mechanism as
      well as synergistic cytotoxic effects were estimated by using MTT assay, DAPI
      staining, agarose gel electrophoresis, flow cytometric analysis, and western blot
      analysis. RESULTS: The combined treatment of two drugs also markedly decreased
      cell viability. The cytotoxic effects of two drugs were revealed as apoptosis
      characterized by chromatin condensation, DNA fragmentation, and the loss of
      mitochondrial membrane potential. The apoptotic cytotoxicity was accompanied by
      activation of caspase-3 protease as well as decreased the expression of Bcl-2,
      Bid, and Bcl-x/L. In addition, the cells treated with combination of two drugs
      also showed significantly increased intracellular reactive oxygen species levels
      and lipid peroxidation compared to cells As(2)O(3) or berberine only. CONCLUSION:
      Combined treatment of As(2)O(3) with berberine induced activation of apoptotic
      signaling pathways in HNB SH-SY5Y cells. These results suggest that the
      possibility of the combined treatment of two chemotherapeutic agents with low
      concentration improving cytotoxic effect for cancer cells with minimal side
      effects.

PMID- 19096577
TI  - Isolated cerebral mucormycosis.
AB  - Isolated cerebral mucoromycosis, without rhino-orbital focus, is an extremely
      rare but life-threatening infection of central nervous system that most commonly
      found in intravenous drug abuser. We present a case of isolated cerebral
      mucormycosis diagnosed by open biopsy and treated with amphotericin B. The
      patient has returned to independent living.

PMID- 19096578
TI  - Extraordinarily long-term posttraumatic cerebrospinal fluid fistula.
AB  - Most posttraumatic cerebrospinal fluid (CSF) leakage is noticed by the patients
      with the first symptom, rhinorrhea. A 38-year-old woman presented with frequent
      clear continuous rhinorrhea and otorrhea for 5 years after basilar skull
      fracture. After this, meningitis was developed with subsequent CSF fistula. Her
      clinical symptom was improved by medical treatment. The dural defect and CSF
      leakage were not detected by computerized tomography (CT) cisternography. We
      report a rare case of persistent posttraumatic CSF fistula that continued for
      five years.

PMID- 19096579
TI  - Craniovertebral junction tuberculosis with atlantoaxial dislocation : a case
      report and review of the literature.
AB  - Craniovertebral junction (CVJ) tuberculosis is a rare disease, potentially
      causing severe instability and neurological deficits. The authors present a case
      of CVJ tuberculosis with atlantoaxial dislocation and retropharyngeal abscess in
      a 28-year-old man with neck pain and quadriparesis. Radiological evaluations
      showed a widespread extradural lesion around the clivus, C1, and C2. Two stage
      operations with transoral decompression and posterior occipitocervical fusion
      were performed. The pathological findings confirmed the diagnosis of
      tuberculosis. Treatment options in CVJ tuberculosis are controversial without
      well-defined guidelines. But radical operation (anterior decompression and
      posterior fusion and fixation) is necessary in patient with neurological deficit
      due to cord compression, extensive bone destruction, and instability or
      dislocation. The diagnosis and treatment options are discussed.

PMID- 19096580
TI  - Pleomorphic xanthoastrocytoma with an intracystic hemorrhage : a case report and
      literature review.
AB  - Pleomorphic xanthoastrocytoma (PXA) has been considered as a low grade tumor of
      adolescents and young adults. Although this tumor often shows cystic component,
      the hemorrhage within the cyst is extremely rare. The authors report a rare case
      of cystic PXA with a hemorrhage within the cyst and the mural nodule in the left
      frontal lobe. A 64-year-old male presented with a week history of the right side
      hemiparesis. After gross total resection of the tumor, the patient was fully
      recovered from neurological deficit. It is suggested that this typically benign
      tumor could be presented with hemorrhage, causing a rapid neurological
      deterioration. Prompt surgical intervention, especially total removal of the
      tumor can provide an excellent functional recovery.

PMID- 19096581
TI  - Occlusion of the middle cerebral artery branch mimicking aneurysm.
AB  - A 26-year-old man was admitted to our department due to intermittent left
      hemiparesis for 3 months. Magnetic resonance image showed subacute infarction in
      the right precentral gyrus. Digital subtraction angiography and magnetic
      resonance angiography revealed an aneurysmal protrusion at the right middle
      cerebral artery (MCA) bifurcation. It was difficult to differentiate the aneurysm
      from the occlusion of the middle trunk of the MCA trifurcation. Brain single
      photon emission computerized tomography showed a decrease in perfusion in the
      right posterior frontal lobe without vascular reserve. Therefore, we planned a
      superficial temporal artery-MCA anastomosis with an exploration of the right MCA
      bifurcation. Intraoperatively, the aneurysmal opacification on preoperative
      angiography proved to be the proximal stump of the occluded middle trunk of the
      MCA trifurcation. An aneurysmal protrusion at the MCA bifurcation does not always
      indicate an aneurysm. In diagnosing protruding vascular lesions at the MCA
      bifurcation, the possibility of a vascular stump should be considered according
      to their angioanatomical appearance and the history of the patient.

PMID- 19096582
TI  - Intracerebral hematoma caused by ruptured traumatic pseudoaneurysm of the middle
      meningeal artery : a case report.
AB  - Hematomas caused by ruptured traumatic pseudoaneurysms of the middle meningeal
      artery (MMA) usually present with extradural hematomas, whereas intradural
      intraparenchymal hematomas are extremely rare. We report a case of traumatic
      pseudoaneurysm of the MMA giving rise to an intracerebral hematoma after head
      trauma. A 70-year-old man suffered a massive intracerebral temporoparietal
      hemorrhage after a head injury. CT angiogram of the brain revealed a large
      hematoma in the right middle cranial fossa extending to the right sylvian
      fissure. Cerebral angiogram also revealed a pseudoaneurysm of the MMA, which was
      successfully treated surgically. Although traumatic MMA pseudoaneurysm producing
      intracerebral hematoma (ICH) is rare, it should be considered as a possible cause
      of intracerebral hematoma.

PMID- 19096583
TI  - Endoscopic discectomy for the cauda equina syndrome during third trimester of
      pregnancy.
AB  - Low back pain is common during pregnancy. However, the prevalence of symtomatic
      lumbar disc herniation is rare, and cauda equina syndrome due to disc herniation
      during pregnancy is even rarer. We report a rare case of lumbar disc herniation
      causing cauda equina syndrome during third trimester of pregnancy which
      successfully treated by endoscopic discectomy. This case shows that endoscopic
      discectomy can be the treatment option for the lumbar disc herniation during
      pregnancy.

PMID- 19096584
TI  - Intracranial atherosclerotic disease; current options for surgical or medical
      treatment.
AB  - Recently, intracranial atherosclerosis has become a major cause of ischemic
      stroke, appearing more frequently in Koreans than Caucasians. Symptomatic or
      asymptomatic intracranial atherosclerosis is a disease that could recur readily
      even during the treatment with anti-platelet agents. When the symptoms develop,
      ischemic stroke can not be recovered readily. Therefore, aggressive treatments
      such as endovascular therapy and bypass surgery are required in addition to
      medical treatment for the intracranial artery stenosis. Recent intracranial
      stenting and drug eluting stenting have shown as very advanced effective
      therapeutic modalities. Nevertheless, until now, a randomized controlled study
      has not been conducted. Regarding bypass surgery, since the failed EC-IC bypass
      surgery study performed 20 years ago, extensive studies on its efficacy has not
      been conducted yet, and thus it has to be performed strictly only in
      hemodynamically compromised patients. Unless breakthrough drugs that suppress the
      progression of intracranial atherosclerosis and the formation of thrombi, and
      facilitate the regression of the arterial stenosis, the treatment concept of the
      recovery of the blood flow of stenotic arterial territory by mechanical
      recanalization or bypass surgery would be remained for the prevention as well as
      treatment of ischemic stroke caused by intracranial atherosclerosis.

PMID- 19096586
TI  - Myelopathy caused by soft cervical disc herniation : surgical results and
      prognostic factors.
AB  - OBJECTIVE: The purpose of this study was to investigate the surgical results and
      prognostic factors for patients with soft cervical disc herniation with
      myelopathy. METHODS: During the last 7 years, 26 patients with cervical
      discogenic myelopathy were undertaken anterior discectomy and fusion. Clinical
      and radiographic features were reviewed to evaluate the surgical results and
      prognostic factors. The clinical outcome was judged using two grading systems
      (Herkowitz's scale and Nurick's grade). RESULTS: Male were predominant (4:1), and
      C5-6 was the most frequently involved level. Gait disturbance, variable degree of
      spasticity, discomfort in chest and abdomen, hand numbness were the most obvious
      signs. Magnetic resonance(MR) images showed that central disc herniation was
      revealed in 16 cases, and accompanying cord signal changes in 4. Postoperatively,
      23 patients showed favorable results (excellent, good and fair) according to
      Herkowitz's scale. CONCLUSION: Anterior cervical discectomy and fusion
      effectively reduced myelopathic symptoms due to soft cervical disc herniation.
      The authors assured that the shorter duration of clinical attention, the lesser
      the degree of myelopathy and better outcome in discogenic myelopathy.

PMID- 19096585
TI  - Spinal cord hemangioblastoma : diagnosis and clinical outcome after surgical
      treatment.
AB  - OBJECTIVE: Spinal cord hemangioblastoma is an uncommon vascular neoplasm with a
      benign nature and is associated with von Hippel-Lindau (VHL) disease in 20-30% of
      patients. Total removal of these tumors without significant neurological deficit
      remains a great challenge. The purpose of this study was to investigate the
      efficacy of VHL mutation analysis and to evaluate surgical outcome of patients
      with spinal cord hemangioblastomas. METHODS: This study included nine patients
      treated for spinal cord hemangioblastomas at our institute between December 1994
      and March 2006. There were four male and five female patients. Mean age was 37.8
      years. The mean follow-up period was 22.4 months. Magnetic resonance imaging
      (MRI) of the complete neuraxis was done in all cases and VHL mutation analysis
      was performed in three cases for a definite diagnosis. RESULTS: Six patients had
      intramedullary tumor, and the remaining patients had intradural extramedullary
      lesions. Five patients were associated with VHL disease. The von Hippel-Lindau
      mutation analysis was done in three patients and two of them showed VHL gene
      abnormality. Tumors were located in the cervical cord in five cases and in the
      thoracic cord in four cases. All patients underwent surgical intervention, and
      total removal was achieved in six cases. All patients showed improvement or, at
      least, clinically stationary state. Surgical complications did not develop in any
      cases. CONCLUSION: Spinal hemangioblastoma in this series has been safely and
      effectively removed via a posterior approach. Postoperatively, clinical outcome
      was excellent in the majority of cases. The VHL mutation analysis was useful in
      patients with family history and in those with multiple hemangioblastomas.

PMID- 19096587
TI  - Persistent trigeminal artery variant detected by conventional angiography and
      magnetic resonance angiography-incidence and clinical significance-.
AB  - OBJECTIVE: Persistent trigeminal artery variant (PTAV) is an anastomosis between
      the internal carotid artery (ICA) and the cerebellar artery without any
      interposing basilar artery segment. We discuss its probable embryological origin
      and emphasize clinical implications. METHODS: Retrospectively 1250 conventional
      cerebral angiograms and 2947 cranial magnetic resonance angiographies (MRAs) were
      evaluated for the patients with PTAV. RESULTS: Five patients (four men and one
      woman, 23 to 76 years of age, median age 65 years) had a PTAV. Three patients who
      underwent MRA had a PTAV (3/2947=0.1%). Four of the patients who underwent
      cerebral angiography had a PTAV (4/1250=0.32%). Two of 143 patients who underwent
      both conventional angiography and cranial MRA showed PTAV. The PTAV was an
      incidental finding in all five patients. The PTAV originated from the cavernous
      segment of the left ICA in four patients and from the cavernous segment of the
      right ICA in one patient. The terminal branch of the PTAV was the anterior
      inferior cerebellar artery (AICA) and superior cerebellar artery (SCA) in two
      patients and the AICA only in the other three patients. CONCLUSION: Neurosurgeons
      should be aware of possible presence of PTAV. Manipulation of this vessel during
      a surgical approach to the parasellar region and percutaneous gasserian ganglion
      procedure may result in hemorrhage or ischemia.

PMID- 19096588
TI  - The anatomical location and course of the facial nerve in vestibular schwannomas
      : a study of 163 surgically treated cases.
AB  - OBJECTIVE: The aim of this study was to identify the anatomical location and
      course of the facial nerve (FN) and their relationship to the tumor size in
      surgically treated vestibular schwannomas. METHODS: A retrospective study was
      conducted on 163 patients who had been treated by the microsurgical resection for
      a newly diagnosed vestibular schwannoma between 1995 and 2005 (mean age of 46.1
      years; 108 females and 55 males). Surgery was carried out via retrosigmoid
      approach in all patients with the electromyographic monitoring for the FN
      function. The anatomical location and course of the FN along the tumor surface
      were verified in each patient during the microsurgery, and were classified into 4
      groups : 1) the FN displaced along the ventral and superior surface of the tumor
      (VS); 2) the ventral and central (VC); 3) the ventral and inferior (VI); and 4)
      the dorsal (Do). RESULTS: THE FN DISPLACEMENT WAS IDENTIFIED AS THE FOLLOWINGS :
      VS in 91 patients (55.8%); VC in 57 (35.0%); VI in 14 (8.6%); and Do in 1 (0.6%).
      In the subgroup with tumors less than 2 cm in diameter (n=23), the FN was
      displaced along the ventral and central surface of the tumor in the majority
      (65.2%), whereas, in the patients with tumors larger than 2cm (n=140), it was
      displaced along the ventral and superior surface most frequently (59.3%).
      CONCLUSION: The FN can be displaced variably in vestibular schwannomas, and most
      frequently along the ventral and superior surface of the tumor, especially in
      large ones.

PMID- 19096589
TI  - Lesion of subthalamic nucleus in parkinsonian rats : effects of dopamine d(1) and
      d(2) receptor agonists on the neuronal activities of the substantia nigra pars
      reticulata.
AB  - OBJECTIVE: It was hypothesized that dopamine agonist administration and
      subthalamic nucleus (STN) lesion in the rat might have a synergistic effect on
      the neuronal activities of substantia nigra pars reticulata (SNpr) as observed in
      patients with Parkinson's disease. The effects of SKF38393 (a D(1) receptor
      agonist) and Quinpirole (a D(2) receptor agonist) were compared in parkinsonian
      rat models with 6- hydroxydopamine (6-OHDA) after STN lesion. METHODS: SKF38393
      and Quinpirole were consecutively injected intrastriatally. SNpr was
      microrecorded to ascertain the activity of the basal ganglia output structure.
      The effect of SKF38393 or Quinpirole injection on the firing rate and firing
      patterns of SNpr was investigated in medial forebrain bundle (MFB) lesioned rats
      and in MFB+STN lesioned rats. RESULTS: The administration of SKF38393 decreased
      SNpr neuronal firing rates and the percentage of burst neurons in the MFB
      lesioned rats, but did not alter them in MFB+STN lesioned rats. The
      administration ofQuinpirole significantly decreased the spontaneous firing rate
      in the MFB lesioned rats. However, after an additional STN lesion, it increased
      the percentage of burst neurons. CONCLUSION: This study demonstrated that
      dopamine agonists and STN lesion decreased the hyperactive firing rate and the
      percentage of burst neurons of SNpr neurons in 6-OHDA lesioned rats,
      respectively. Quinpirole with STN lesion increased a percentage of burst neurons.
      To clear the exact interactive mechanism of D(1) and D(2) agonist and the
      corresponding location, it should be followed a study using a nonselective
      dopamine agonist and D(1), D(2) selective antagonist.

PMID- 19096590
TI  - The VR1-Positive Primary Afferent-Mediated Expression of pERK in the Lumbosacral
      Neurons in Response to Mechanical and Chemical Stimulation of the Urinary Bladder
      in Rats.
AB  - OBJECTIVE: This study characterized the neurons in the lumbosacral cord that
      express phospho ERK (pERK) after distension or irritation of the bladder, and
      their relation to the vanilloid receptor 1 (VR1) positive primary afferents.
      METHODS: Mechanical distension and chemical irritation of the bladder were
      induced by intravesical injection of the saline and mustard oil, respectively.
      Spinal neurons expressing pERK and the primary afferent fibers were characterized
      using multiple immunofluorescence for neurokinin 1 (NK1), neuronal nitric oxide
      synthetase (nNOS) and VR1. RESULTS: Neurons in lamina I, medial dorsal horn
      (MDH), dorsal gray commissure (DGC) and sacral parasympathetic nucleus (SPN) were
      immunoreactive for pERK after either mechanical or chemical stimulation. The
      majority of pERK positive cells were positive for NK1 in lamina I and SPN, but
      not in the DGC. Most of pERK positive cells are not stained for nNOS except in a
      small population of the cells in the SPN and DGC. Contacts between perikarya and
      dendrites of pERK-positive cells and terminals of primary afferents expressing
      VR1 were identified in lamina I, lateral collateral path (LCP) and SPN.
      CONCLUSION: In this study, the lumbosacral neurons activated by mechanical and
      chemical stimulation of the urinary bladder were identified with expression of
      the pERK, and also provided the evidence that VR1-positive primary afferents may
      mediate the activation of these neurons.

PMID- 19096591
TI  - Identification of Novel Metabolic Proteins Released by Insulin Signaling of the
      Rat Hypothalmus Using Liquid Chromatography-Mass Spectrometry (LC-MS).
AB  - OBJECTIVE: The brain is dependent on glucose as an energy source. Intricate
      homeostatic mechanisms have been implicated in maintaining the blood glucose
      concentration in the brain. The aim of this study is to find the way to identify
      the metabolic proteins regulating the glucose in rat hypothalamus. METHODS: In
      this study, we analysed the secretome from rat hypothalamus in vivo. We
      introduced 500 nM of insulin into the rat hypothalamus. The chromatographic
      patterns of the secretome were identified, after which Mass Spectrometry-Mass
      Spectrometry (MS-MS) analysis was performed. RESULTS: In Liquid Chromatography
      Mass Spectrometry (LC-MS) analysis, 60 proteins were identified in the secretome.
      Among them, 8 novel proteins were unveiled and were associated with the energy
      metabolism of insulin signaling in mitochondria of rat hypothalamic neuron.
      Nineteen other proteins have unknown functions. These ligands were confirmed to
      be secreting from the rat hypothalmus on insulin signaling by western blotting.
      CONCLUSION: The hypothalamus is the master endocrine gland responsible for the
      regulation of various physiological and metabolic processes. Proteomics using LC
      MS analysis offer a efficient means for generating a comprehensive analysis of
      hypothalamic protein expression by insulin signaling.

PMID- 19096592
TI  - Spinal drop metastasis from a posterior fossa choroid plexus papilloma.
AB  - Choroid plexus papillomas (CPPs) are typically considered as benign tumors, with
      a favorable long-term prognosis. Drop metastasis of CPP into the spinal
      subarachnoid space is rare. We report a 42-year-old woman who presented with
      headache and back pain 6 years after removal of a posterior fossa CPP. Magnetic
      resonance imaging revealed mass lesions in the lumbosacral subarachnoid space and
      recurrent intracranial tumor. The lesions were resected and histologically
      diagnosed was CPP. We consider that CPP can spread via cerebrospinal fluid
      pathways and cause spinal drop metastasis. Therefore, it is necessary to evaluate
      the whole spinal axis and to perform periodic follow-up examinations in patients
      with CPP.

PMID- 19096593
TI  - Distal Middle Cerebral Artery M4 Aneurysm Surgery Using Navigation-CT
      Angiography.
AB  - Unruptured non-traumatic dissecting aneurysm in the M4 segment of the middle
      cerebral artery (MCA) accompanied by complete occlusion of the ipsilateral
      internal cerebral artery (ICA) has never been reported. A 41-year-old man
      presented with an infarction manifesting as left-sided weakness and dysarthria.
      Magnetic resonance angiography revealed a subacute stage infarction in the right
      MCA territory and complete occlusion of the right ICA. Angiography demonstrated
      aneurysmal dilatation of the M4 segment of the right MCA. Surgery was performed
      to prevent hemorrhage from the aneurysm. The aneurysm was proximally clipped
      guided by Navigation-CT angiography and flow to the distal MCA was restored by
      superficial temporal artery-middle cerebral artery (STA-MCA) anastomosis. We
      report this rare case with literature review.

PMID- 19096594
TI  - Lumbosacral plexopathy, complicating rhabdomyolysis in a 57-year-old man,
      presented with sudden weakness in both legs.
AB  - A 57-year-old man presented with weakness in both legs upon awakening after
      drinking. Magnetic resonance imaging (MRI) of the lumbar spine did not reveal any
      intraspinal abnormalities but MRI of the pelvis revealed lesions with abnormal
      intensities with heterogeneous contrast enhancement in both gluteal muscles.
      Serum creatine phosphokinase was markedly elevated. A diagnosis of lumbosacral
      plexopathy, complicating rhabdomyolysis was made. With supportive care he
      recovered well but mild weakness of the right ankle remained at 6 month-follow
      up. Pelvic MRI is a helpful diagnostic tool in localizing rhabdomyolysis.
      Lumbosacral plexopathy should be included in the differential diagnosis of the
      such cases, presenting with sudden weakness of legs.

PMID- 19096595
TI  - Radiculopathy caused by internal iliac artery pseudoaneurysm managed with
      endovascular embolization.
AB  - The authors describe a case of pseudoaneurysm arising from internal iliac artery
      presented with radiculopathy mimicking the symptoms of lumbar disc disease or
      spinal cord tumor. Among the several preoperative evaluation including CT, MRI,
      electrophysiologic study and ultrasonography, important diagnostic clue was
      obtained by ultrasonographic findings of turbulence flow at the core of partially
      enhanced mass in the pelvic cavity. The patient was managed with endovascular
      coil embolization successfully. The current case makes us remind that assessment
      of neurological symptoms on lower extremity should include consideration of
      extraspinal cause in pelvis.

PMID- 19096596
TI  - Complete Cord Injury after Minimal Trauma in a Patient with Forestier's Disease
      Accompanying Ossification of the Posterior Longitudinal Ligament.
AB  - Forestier's disease is a systemic rheumatological abnormality in which exuberant
      ossification occurs along ligaments throughout the body, but most notably the
      anterior longitudinal ligament of the spine. This disease is usually
      asymptomatic; however dysphagia, dyspnea, and peripheral nerve entrapment have
      all been documented in association with the disorder. We report a rare case of
      catastrophic neurologic damage caused by Forestier's disease accompanying
      ossification of the posterior longitudinal ligament.

PMID- 19096597
TI  - Pneumorrhachis and paraspinal air with vacuum disc : case report and literature
      review.
AB  - Air within the spinal canal called pneumorrhachis has been seen rarely. We report
      a case showing multiple air pockets in the paraspinal and epidural space with
      vacuum disc and review pathogenesis and treatment of pneumorrhachis.

PMID- 19096598
TI  - A case of myelopathy after intrathecal injection of fluorescein.
AB  - We present a case with seizure, confusion, hypesthesia and paraplegia after
      intrathecal injection of fluorescein. A 41-year-old man was admitted to our
      institution for the management of the CSF leakage. Intrathecal injection of
      fluorescein was performed and he complained of severe pain and numbness in the
      lower extremities at the end of the injection. Four hours later, he exhibited
      confusion, paraparesis and two episodes of generalized seizures. Two days later,
      he showed paraplegia and all sensory modalities below the T12 level were absent.
      Spine magnetic resonance imaging revealed myelopathic change in the lower
      thoracic spinal cord. There was no improvement of weakness and sensory deficits
      in lower extremity even 14 days after fluorescein injection. We speculated that
      thoracic myelopathy was associated with the intrathecal injection of fluorescein.
      In spite of its rarity, the complication after intrathecal injection of
      fluorescein could be serious. Thus, obtaining an informed consent with discussion
      with patient before the procedure is mandatory.

PMID- 19096599
TI  - Lumbo-sacro-pelvic Fixation Using Iliac Screws for the Complex Lumbo-sacral
      Fractures.
AB  - Fractures of lumbo-sacral junction involving bilateral sacral wings are rare.
      Posterior lumbo-sacral fixation does not always provide with sufficient stability
      in such cases. Various augmentation techniques including divergent sacral ala
      screws, S2 pedicle screws and Galveston rods have been reported to improve lumbo
      sacral stabilization. Galveston technique using iliac bones would be the best
      surgical approach especially in patients with bilateral comminuted sacral
      fractures. However, original Galveston surgery is technically demanding and
      bending rods into the appropriate alignment is time consuming. We present a
      patient with unstable lumbo-sacral junction fractures and comminuted U-shaped
      sacral fractures treated by lumbo-sacro-pelvic fixation using iliac screws and
      discuss about the advantages of the iliac screws over the rod system of Galveston
      technique.

PMID- 19096600
TI  - Clinical experience of the dynamic stabilization system for the degenerative
      spine disease.
AB  - OBJECTIVE: The aim of the present study was to assess the safety and efficacy of
      the dynamic stabilization system in the treatment of degenerative spinal
      diseases. METHODS: The study population included 20 consecutive patients (13
      females, 7 males) with a mean age of 61+/-6.98 years (range 46-70) who underwent
      decompression and dynamic stabilization with the Dynesys system between January
      2005 and August 2006. The diagnoses included spinal stenosis with degenerative
      spondylolisthesis (9/20, 45%), degenerative spinal stenosis (5/20, 25%), adjacent
      segmental disease after fusion (3/20, 15%), spinal stenosis with degenerative
      scoliosis (2/20, 10%) and recurrent intervertebral lumbar disc herniation (1/20,
      5%). All of the patients completed the visual analogue scale (VAS) and the Korean
      version of the Oswestry Disability Index (ODI). The following radiologic
      parameters were measured in all patients : global lordotic angles and segmental
      lordotic angles (stabilized segments, above and below adjacent segments). The
      range of motion (ROM) was then calculated. RESULTS: The mean follow-up period was
      27.25+/-5.16 months (range 16-35 months), and 19 patients (95%) were available
      for follow-up. One patient had to have the implant removed. There were 30
      stabilized segments in 19 patients. Monosegmental stabilization was performed in
      9 patients (47.3%), 9 patients (47.3%) underwent two segmental stabilizations and
      one patient (5.3%) underwent three segmental stabilizations. The most frequently
      treated segment was L4-5 (15/30, 50%), followed by L3-4 (12/30, 40%) and L5-S1
      (3/30, 10%). The VAS decreased from 8.55+/-1.21 to 2.20+/-1.70 (p<0.001), and the
      patients' mean score on the Korean version of the ODI improved from 79.58%+/
      15.93% to 22.17%+/-17.24% (p<0.001). No statistically significant changes were
      seen on the ROM at the stabilized segments (p=0.502) and adjacent segments (above
      segments, p=0.453, below segments, p=0.062). There were no patients with implant
      failure. CONCLUSION: The results of this study show that the Dynesys system could
      preserve the motion of stabilized segments and provide clinical improvement in
      patients with degenerative spinal stenosis with instability. Thus, dynamic
      stabilization systems with adequate decompression may be an alternative surgical
      option to conventional fusion in selected patients.

PMID- 19096601
TI  - Clinical factors for the development of posttraumatic hydrocephalus after
      decompressive craniectomy.
AB  - OBJECTIVE: Earlier reports have revealed that the incidence of posttraumatic
      hydrocephalus (PTH) is higher among patients who underwent decompressive
      craniectomy (DC). The aim of this study was to determine the influencing factors
      for the development of PTH after DC. METHODS: A total of 693 head trauma patients
      admitted in our hospital between March 2004 and May 2007 were reviewed. Among
      thee, we analyzed 55 patients with severe traumatic brain injury who underwent
      DC. We excluded patients who had confounding variables. The 33 patients were
      finally enrolled in the study and data were collected retrospectively for these
      patients. The patients were divided into two groups: non-hydrocephalus group
      (Group I) and hydrocephalus group (Group II). Related factors assessed were
      individual Glasgow Coma Score (GCS), age, sex, radiological findings, type of
      operation, re-operation and outcome. RESULTS: Of the 693 patients with head
      trauma, 28 (4.0%) developed PTH. Fifty-five patients underwent DC and 13 (23.6%)
      developed PTH. Eleven of the 33 study patients (30.3%) who had no confounding
      factors were diagnosed with PTH. Significant differences in the type of
      craniectomy and re-operation were found between Group I and II. CONCLUSION: It is
      suggested that the size of DC and repeated operation may promote posttraumatic
      hydrocephalus in severe head trauma patients who underwent DC.

PMID- 19096602
TI  - Removal of intradural-extramedullary spinal cord tumors with unilateral limited
      laminectomy.
AB  - Total laminectomy for the removal of intradural-extramedullary spinal cord tumors
      has been used widely, but postoperative complications often develop, such as
      kyphosis, spinal instability, and persistent back pain. In this study, we
      evaluated seven patients with intradural-extramedullary spinal cord tumors with
      respect to the value of unilateral limited laminectomy. Our cases included six
      schwannomas, and one meningioma. The cervical region was involved in four cases,
      the thoracolumbar region in two cases, and the lumbar region in one case. The
      rationale for choosing a unilateral approach is to preserve musculoligamentous
      attachments and posterior bony elements as much as possible. The patients were
      mobilized on the third postoperative day and preoperative neurological symptoms
      were recovered within a few weeks. We did not observe any complication relating
      to unilateral limited laminectomy and at follow-up evaluation (at 3 and 12 months
      postoperatively), none of the patients showed spinal deformity or spinal
      instability. We think that the unilateral limited laminectomy is a safe and
      efficient technique for the treatment of intradural-extramedullary spinal cord
      tumors. We suggest that this technique is one of the best treatments for these
      tumors.

PMID- 19096603
TI  - Myoclonus induced by the use of gabapentin.
AB  - Myoclonus is a rare side effect of gabapentin (GBP) and has been reported in
      patients with preexisting myoclonus, mental retardation, chronic static
      encephalopathy, diffuse brain damage, impaired renal function, or end stage renal
      disease. We report a case of myoclonus in a patient with normal renal function
      and no previous disorders. A 69-year-old female underwent diskectomy and
      foraminotomy at the left L4-L5 level. Postoperatively, she complained of
      paresthesia in her left leg, which was thought to be due to root manipulation
      during surgery. To relieve the paresthesia, she was given tramadol, an oral
      opioid agonist, and GBP. One week after GBP was increased to 900 mg per day,
      myoclonus developed, which severely impaired her normal activity. Her symptoms
      resolved 2 days after discontinuation of GBP. The coadministration of tramadol
      and GBP may mutually enhance the myoclonic potential of each drug. The causal
      relationship between GBP and myoclonus was suggested by cessation of myoclonus
      after GBP discontinuation despite continued therapy with tramadol.

PMID- 19096604
TI  - Posterior epidural migration of thoracic disc fragment.
AB  - Migration of a disc fragment to the posterior epidural space is rare, especially
      in the thoracic spine. Only four such cases of posterior epidural migration of
      thoracic disc fragments have been reported. The authors report a case of 66-year
      old man who presented with back pain and right leg weakness due to posterior
      epidural migration of thoracic disc fragment. The patient was successfully
      treated by laminectomy and partial facetectomy with disc removal.

PMID- 19096605
TI  - Spinal subdural hemorrhage as a cause of post-traumatic delirium.
AB  - A 64-year-old man with TBI was admitted to our institute. In following days, he
      showed unusual behavior of agitation, restlessness, emotional instability and
      inattention. Post-traumatic delirium was tentatively diagnosed, and donepezil was
      given for his cognitive dysfunction. Although there was partial relief of
      agitation, he sustained back pain despite medication. Lumbar magnetic resonance
      image revealed SDH along the whole lumbar spine, and surgical drainage was
      followed. Postoperatively, his agitation disappeared and further medication was
      discontinued. We report a unique case of post-traumatic delirium in a patient
      with concomitant TBI and spinal subdural hemorrhage (SDH) that resolved with
      operative drainage of spinal hemorrhage.

PMID- 19096606
TI  - Pituitary Apoplexy due to Pituitary Adenoma Infarction.
AB  - Cause of pituitary apoplexy has been known as hemorrhage, hemorrhagic infarction
      or infarction of pituitary adenoma or adjacent tissues of pituitary gland.
      However, pituitary apoplexy caused by pure infarction of pituitary adenoma has
      been rarely reported. Here, we present the two cases pituitary apoplexies caused
      by pituitary adenoma infarction that were confirmed by transsphenoidal approach
      (TSA) and pathologic reports. Pathologic report of first case revealed total
      tumor infarction of a nonfunctioning pituitary macroadenoma and second case
      partial tumor infarction of ACTH secreting pituitary macroadenoma. Patients with
      pituitary apoplexy which was caused by pituitary adenoma infarction unrelated to
      hemorrhage or hemorrhagic infarction showed good response to TSA treatment.
      Further study on the predisposing factors of pituitary apoplexy and the mechanism
      of infarction in pituitary adenoma is necessary.

PMID- 19096607
TI  - Unusual Intracranial Parasagittal Meningioma Extending into the Internal Jugular
      Vein through the Sinuses.
AB  - Meningiomas frequently invade cerebral venus sinuses, especially parasagittal
      meningioma to superior sagittal sinus. However, most invasions do not reach
      internal jugular vein. We present a case of parasagittal meningioma extending
      into the internal jugular vein through the sinuses. Radiological investigation
      revealed that the tumor was invading the sagittal, transverse, sigmoid sinus and
      junction of the internal jugular vein to subclavian vein, which was filled with
      tumor. The histopathological examinations revealed that both the cerebral tumor
      and mass in the internal jugular vein contributed to the transitional meningioma.
      This is a rare case of a meningioma extending into the internal jugular vein
      through the sinuses. According to this case, the frontal parasagittal meningioma
      could invade directly the internal jugular vein. The significance of this
      association to cerebral venus sinuses and internal jugular vein are discussed.

PMID- 19096609
TI  - Inter-racial, gender and aging influences in the length of anterior commissure
      posterior commissure line.
AB  - OBJECTIVE: The length of anterior-posterior commissure (AC-PC) in racial groups,
      age, gender of patients with deep brain stimulation (DBS) and pallidotomy were
      investigated. METHODS: From January 1996 to December 2003, 211 patients were
      treated with DBS and pallidotomy. There were 160 (76%) Caucasians, 35 (17%)
      Hispanics, 12 (5%) Asians and 4 Blacks (2%). There were 88 males and 52 females
      in DBS-surgery group and 44 males, 27 females in pallidotomy group. Mean age was
      58 year-old. There were 19 males and 19 females and mean age was 54.7 years in
      the control group. Measurements were made on MRI and @Target software. RESULTS:
      The average AC-PC distance was 24.89 mm (range 32 to 19), which increased with
      aging until 75 years old in Caucasian and also increased with aging in Hispanic,
      but the AC-PC distance peaked at 45 years old in Hispanic. The order of AC-PC
      distance were 25.2+/-2 mm in Caucasian, 24.6+/-2.24 mm in Asian, 24.53 mm in
      Black, 23.6+/-1.98 mm in Hispanic. The average AC-PC distance in all groups was
      24.22 mm in female who was mean age of 56.35, 25.28 mm in male who was mean age
      of 60.19 and 24.5+/-2 mm in control group that was excluded because of the
      difference of thickness of slice. According to multiple regression analysis, the
      AC-PC distance was significantly correlated with age, race, and gender.
      CONCLUSION: The AC-PC distance is significantly correlated with age, gender, and
      race. The atlas of functional stereotaxis would be depended on the variation of
      indivisual brain that can influenced by aging, gender, and race.

PMID- 19096608
TI  - Current status and future prospect of endovascular neurosurgery.
AB  - Recently, due to the evolution of technology, the field of neurosurgery is
      receiving spotlight. In particular endovascular neurosurgery has gained a great
      interest along with the advancement of the modern neurosurgery. The most
      remarkable advances were made in embolization of the cerebral aneurysms,
      arteriovenous malformations and intracranial stenosis during the past 10 years.
      These advances will further change the role of neurosurgeons in treating
      cerebrovascular disease. Because interventional neuroradiologists have performed
      most of procedures in the past, neurosurgeons have been deprived of chances to
      learn endovascular procedure. This article discusses the development of
      technological aspect of endovascular neurosurgery in chronological order. By
      understanding the history and current status of the endovascular surgery, the
      future of neurosurgery will be promising.

PMID- 19096610
TI  - Analysis of failed spinal cord stimulation trials in the treatment of intractable
      chronic pain.
AB  - OBJECTIVE: The purpose of this study is to identify the factors affecting the
      failure of trials (<50% pain reduction in pain for trial period) to improve
      success rate of spinal cord stimulation (SCS) trial. METHODS: A retrospective
      review of the failed trials (44 patients, 36.1%) among the patients (n=122) who
      underwent SCS trial between January 1990 and December 1998 was conducted. We
      reviewed the causes of failed trial stimulation, age, sex, etiology of pain, type
      of electrode, and third party support. RESULTS: Of the 44 patients, 65.9% showed
      unacceptable pain relief in spite of sufficient paresthesia on the pain area with
      trial stimulation. Four of six patients felt insufficient paresthesia with
      stimulation had the lesions of the spinal cord. Seventy five percent of the
      patients experienced unpleasant or painful sensation during stimulation had
      allodynia dominant pain. Third-party involvement, sex, age and electrode type had
      no influence on the outcome. CONCLUSION: We conclude that SCS trial is less
      effective for patients with neuropathic pain of cord lesions, postherpetic
      neuropathy or post-amputation state. Further, patients with allodynia dominant
      pain can feel unpleasant or painful during trial stimulation.

PMID- 19096611
TI  - Impact of cardio-pulmonary and intraoperative factors on occurrence of cerebral
      infarction after early surgical repair of the ruptured cerebral aneurysms.
AB  - OBJECTIVE: Delayed ischemic deficit or cerebral infarction is the leading cause
      of morbidity and mortality after aneurysmal subarachnoid hemorrhage (SAH). The
      purpose of this study is to reassess the prognostic impact of intraoperative
      elements, including factors related to surgery and anesthesia, on the development
      of cerebral infarction in patients with ruptured cerebral aneurysms. METHODS:
      Variables related to surgery and anesthesia as well as predetermined factors were
      all evaluated via a retrospective study on 398 consecutive patients who underwent
      early microsurgery for ruptured cerebral aneurysms in the last 7 years. Patients
      were dichotomized as following; good clinical grade (Hunt-Hess grade I to III)
      and poor clinical grade (IV and V). The end-point events were cerebral
      infarctions and the clinical outcomes were measured at postoperative 6 months.
      RESULTS: The occurrence of cerebral infarction was eminent when there was an
      intraoperative rupture, prolonged temporary clipping and retraction time,
      intraoperative hypotension, or decreased O(2) saturation, but there was no
      statistical significance between the two different clinical groups. Besides the
      Fisher Grade, multiple logistic regression analyses showed that temporary
      clipping time, hypotension, and low O(2) saturation had odds ratios of 1.574,
      3.016, and 1.528, respectively. Cerebral infarction and outcome had a meaningful
      correlation (gamma=0.147, p=0.038). CONCLUSION: This study results indicate that
      early surgery for poor grade SAH patients carries a significant risk of ongoing
      ischemic complication due to the brain's vulnerability or accompanying cardio
      pulmonary dysfunction. Thus, these patients should be approached very cautiously
      to overcome any anticipated intraoperative threat by concerted efforts with neuro
      anesthesiologist in point to point manner.

PMID- 19096612
TI  - Neurochemical Characterization of the TRPV1-Positive Nociceptive Primary
      Afferents Innervating Skeletal Muscles in the Rats.
AB  - OBJECTIVE: Transient receptor potential vanilloid subfamily type 1 (TRPV1), a
      most specific marker of the nociceptive primary afferent, is expressed in
      peptidergic and non-pepetidergic primary afferents innervating skin and viscera.
      However, its expression in sensory fibers to skeletal muscle is not well known.
      In this study, we studied the neurochemical characteristics of TRPV1-positive
      primary afferents to skeletal muscles. METHODS: Sprague-Dawley rats were injected
      with total 20 microl of 1% fast blue (FB) into the gastrocnemius and erector
      spinae muscle and animals were perfused 4 days after injection. FB-positive cells
      were traced in the L4-L5 (for gastrocnemius muscle) and L2-L4 (for erector spinae
      muscle) dorsal root ganglia. The neurochemical characteristics of the muscle
      afferents were studied with multiple immunofluorescence with TRPV1, calcitonin
      gene-related peptide (CGRP) and P2X(3). To identify spinal neurons responding to
      noxious stimulus to the skeletal muscle, 10% acetic acids were injected into the
      gastrocnemius and erector spinae muscles and expression of phospho extracellular
      signal-regulated kinase (pERK) in spinal cords were identified with
      immunohistochemical method. RESULTS: TRPV1 was expressed in about 49% of muscle
      afferents traced from gastrocnemius and 40% of erector spinae. Sixty-five to 60%
      of TRPV1-positive muscles afferents also expressed CGRP. In contrast, expression
      of P2X(3) immnoreaction in TRPV1-positive muscle afferents were about 20%. TRPV1
      positive primary afferents were contacted with spinal neurons expressing pERK
      after injection of acetic acid into the muscles. CONCLUSION: It is consequently
      suggested that nociception from skeletal muscles are mediated by TRPV1-positive
      primary afferents and majority of them are also peptidergic.

PMID- 19096613
TI  - Midline glioblastoma multiforme with bilateral symmetric cysts.
AB  - Cystic glioblastoma multiforme (GBM) is a rare disease. Its exact prevalence has
      not yet been reported. Also, the mechanism of cyst formation remains to be
      elucidated. We report a case of GBM with a large peripheral cyst. A 43-year-old
      woman visited our clinic with a 3-month history of severe headache, memory
      impairment and general weakness. T1-weighted gadolinium-enhanced magnetic
      resonance (MR) image revealed a midline enhanced solid mass and bilateral
      symmetric banana-shaped peripheral cysts. A centrally enhanced mass was measured
      2x4 cm in size and both mass and cysts as 7x7 cm. Both the frontal lobe and the
      frontal horn were severely compressed inferiorly and posteriorly. We resected a
      midline solid tumor and cysts via the bilateral interhemispheric transcortical
      approach. Histopathologic examination revealed GBM. The patient was subsequently
      treated with fractionated conventional brain radiation therapy, followed by
      temozolomide chemotherapy. Eighteen months later, there was no tumor recurrence
      and no neurological deficits were noted. Our patient showed no tumor recurrence
      and a long survival at a long follow-up.

PMID- 19096615
TI  - Troublesome occipital neuralgia developed by c1-c2 harms construct.
AB  - Recently, Harms and Melcher modified Goel's approach, the C1 lateral mass and C2
      pedicle screw fixation, and the new technique is currently in favor among
      neurosurgeons. Comparing to the advantages of Harms construct, the disadvantages
      were not extensively investigated. We experienced a patient with severe occipital
      pain developed after the C1 lateral mass screw placement for the traumatic
      atlantoaxial instability. We reviewed literatures about Harms construct with
      focus on the occipital neuralgia as a postoperative complication and suggest here
      technical tips to avoid the troublesome pain.

PMID- 19096614
TI  - Cubital tunnel syndrome, associated with synovial chondromatosis.
AB  - A 62-year-old female patient suffered from numbness and resting pain in the right
      ring and little fingers for 3 years. We confirmed cubital tunnel syndrome with
      electrodiagnostic study and performed the operation. We found seven firm
      consistent nodules, compressing the overlying the ulnar nerve, proximal to the
      medial epicondyle in the operation field. Histological finding showed synovial
      chondromatosis. We report a rare case of a patient with cubital tunnel syndrome
      caused by synovial chondromatosis.

PMID- 19096616
TI  - Paraplegia due to Spinal Cord Infarction After Lifting Heavy Objects.
AB  - Spinal cord infarction is uncommon and usually presents with sudden onset of
      motor and sensory disturbances. We report a case of a 64-year-old women without
      previous medical history, who presented with acute onset of paraplegia after
      lifting. However, radiologic examinations did not show any abnormal lesion in the
      spinal cord. And, cerebrospinal fluid studies also showed no remarkable findings.
      This case illustrates the cause of spontaneous paraplegia after lifting injury
      and we consider the presumptive cause of paraplegia as spinal cord infarction.

PMID- 19096617
TI  - Severe vertebral erosion by huge symptomatic pulsating aortic aneurysm.
AB  - Aortic abdominal aneurysm rarely has been reported as causing osteolytic lesions
      of the spine. It may produce back and radiating pain patterns similar to those of
      several commonly encountered neurosurgical processes. We report a uncommon
      complication of huge pulsating aortic aneurysm causing severe vertebral erosion
      with incapacitating back and radiating pain.

PMID- 19096618
TI  - Modified trajectory of c2 laminar screw - double bicortical purchase of the
      inferiorly crossing screw.
AB  - The crossing laminar screw fixation might be the most recently developed approach
      among various fixation techniques for C2. The new construct has stability
      comparable to transarticular or transpedicular screw fixation without risk of
      vertebral artery injury. Quantitative anatomical studies about C2 vertebra
      suggest significant variation in the thickness of C2 lamina as well as cross
      sectional area of junction of lamina and spinous process. We present an elderly
      patient who underwent an occipito-cervical stabilization incorporating crossed C2
      laminar screw fixation. We preoperatively recognized that she had low profiles of
      C2 lamina, and thus made a modification of trajectory for the inferiorly crossing
      screw. We introduce a simple modification of crossing C2 laminar screw technique
      to improve stability in patients with low laminar profiles.

PMID- 19096619
TI  - Analysis of Clip-induced Ischemic Complication of Anterior Choroidal Artery
      Aneurysms.
AB  - OBJECTIVE: The surgical approach is typically similar to those used for other
      supraclinoid internal carotid artery (ICA) lesions. However, the surgical
      clipping of this aneurysm is complicated and as a result, can result in
      postoperative ischemic complications. We studied to clarify the clip-induced
      ischemic complication risk of AChA aneurysm and to get the benefits for helping
      decision making. METHODS: We retrospectively investigated 53 cases (4.0%) of AchA
      aneurysm treated surgically. We divided the AChA aneurysm to 3 subtype according
      to the origin of aneurysmal neck; A type originating from the AChA itself, J type
      from junction of AChA and ICA, and I type from the ICA itself. We evaluated brain
      CT about 1 week post-operative day to confirm the low density in AChA territory.
      RESULTS: Ruptured aneurysm was 26 cases and unruptured aneurysm 27 cases. The
      aneurysmal subtype of A, J, and I was 13, 17, and 23 cases. Of the 53 cases who
      performed surgical neck clipping, twelve (22.6%) had postoperative AChA
      distribution infarcts. Increased infarct after neck clipping had statistic
      significance in non-I subtype (p=0.005). CONCLUSION: It is easy to classify as
      "easy" surgery. But surgery for AChA aneurysms carries with it a significant risk
      of postoperative stroke. Don't always stick to clipping only, especially in non-I
      type of incidental small aneurysm, which has high risk of post-clip ischemic
      complications.

PMID- 19096620
TI  - Spinal schwannoma; analysis of 40 cases.
AB  - OBJECTIVE: This study is to report our experience of 40 cases of spinal
      schwannoma. METHODS: From 1995 to 2006, medical records were retrospectively
      reviewed in 40 cases of spinal schwannoma. RESULTS: We treated 40 spinal
      schwannomas in 38 (22 male and 16 female) patients. The mean age was 50.2. Four
      cases were sited in the cervical spine, 11 cases in the thoracic spine, and 25
      cases in the lumbar spine. Two patients showed recurrences. Thirty-eight cases
      were intradural-extramedullary type and 2 cases were extradural. Two cases (5%)
      including 1 recurred case had no postoperative motor improvement. Ninety-five
      percents of patients improved on postoperative motor grade. CONCLUSION: Spinal
      schwannoma is mostly benign and extramedullary tumor. There were 2 recurred cases
      (5%) that had history of previous subtotal removal at first operation and had
      shown worse prognosis compared with the cases without recurrence. To reduce the
      recurrence of spinal schannoma, total excision of tumor mass should be done.

PMID- 19096621
TI  - Efficacy of spinal implant removal after thoracolumbar junction fusion.
AB  - OBJECTIVE: The purpose of this study was to evaluate the efficacy of spinal
      implant removal and to determine the possible mechanisms of pain relief. METHODS:
      Fourteen patients with an average of 42 years (from 22 to 67 years) were
      retrospectively evaluated. All patients had posterior spinal instrumentation and
      fusion, who later developed recurrent back pain or persistent back pain despite a
      solid fusion mass. Patients' clinical charts, operative notes, and preoperative x
      rays were evaluated. Relief of pain was evaluated by the Visual Analog Scale
      (VAS) pain change after implant removal. Clinical outcome using VAS and modified
      MacNab's criteria was assessed on before implant removal, 1 month after implant
      removal and at the last clinical follow-up. Radiological analysis of sagittal
      alignment was also assessed. RESULTS: Average follow-up period was 18 months
      (from 12 to 25 months). There were 4 patients who had persistent back pain at the
      surgical site and 10 patients who had recurrent back pain. The median time after
      the first fusion operation and the recurrence of pain was 6.5 months (from 3 to
      13 months). All patients except one had palpation pain at operative site. The
      mean blood loss was less than 100ml and there were no major complications. The
      mean pain score before screw removal and at final follow up was 6.4 and 2.9,
      respectively (p<0.005). Thirteen of the 14 patients were graded as excellent and
      good according to modified MacNab's criteria. Overall 5.9 degrees of sagittal
      correction loss was observed at final follow up, but was not statistically
      significant. CONCLUSION: For the patients with persistent or recurrent back pain
      after spinal instrumentation, removal of the spinal implant may be safe and an
      efficient procedure for carefully selected patients who have palpation pain and
      are unresponsive to conservative treatment.

PMID- 19096622
TI  - Incidence and risk factors of acute postoperative delirium in geriatric
      neurosurgical patients.
AB  - OBJECTIVE: Postoperative delirium (POD) is characterized by an acute change in
      cognitive function and can result in longer hospital stays, higher morbidity
      rates, and more frequent discharges to long-term care facilities. In this study,
      we investigated the incidence and risk factors of POD in 224 patients older than
      70 years of age, who had undergone a neurosurgical operation in the last two
      years. METHODS: Data related to preoperative factors (male gender, >70 years,
      previous dementia or delirium, alcohol abuse, serum levels of sodium, potassium
      and glucose, and co morbidities), perioperative factors (type of surgery and
      anesthesia, and duration of surgery) and postoperative data (length of stay in
      recovery room, severity of pain and use of opioid analgesics) were
      retrospectively collected and statistically analyzed. RESULTS: POD appeared in 48
      patients (21.4%) by postoperative day 3. When we excluded 26 patients with
      previous dementia or delirium, 17 spontaneously recovered by postoperative day
      14, while 5 patients recovered by postoperative 2 months with medication, among
      22 patients with newly developed POD. The univariate risk factors for POD
      included previously dementic or delirious patients, abnormal preoperative serum
      glucose level, pre-existent diabetes, the use of local anesthesia for the
      operation, longer operation time (>3.2 hr) or recovery room stay (>90 min), and
      severe pain (VAS>6.8) requiring opioid treatment (p<0.05). Backward regression
      analysis revealed that previously dementic patients with diabetes, the operation
      being performed under local anesthesia, and severe postoperative pain treated
      with opioids were independent risk factors for POD. CONCLUSION: Our study shows
      that control of blood glucose levels and management of pain during local
      anesthesia and in the immediate postoperative period can reduce unexpected POD
      and help preventing unexpected medicolegal problems and economic burdens.

PMID- 19096623
TI  - The Relation Between Sox9, TGF-beta1, and Proteoglycan in Human Intervertebral
      Disc Cells.
AB  - OBJECTIVE: The aim of this study is to elucidate the effects of transforming
      growth factor-beta (TGF-beta)1 and L-ascorbic acid on proteoglycan synthesis, and
      the relationship between Sox9, proteoglycan, and TGF-beta1 in intervertebral disc
      cells. METHODS: Human intervertebral disc tissue was sequentially digested to
      0.2% pronase and 0.025% collagenase in DMEM/F-12 media and extracted cells were
      cultured in 37, 5% CO(2) incubator. When intervertebral disc cells were cultured
      with TGF-beta1 or L-ascorbic acid, the production level of sulfated
      glycosaminoglycan (sGAG) was estimated by dimethyl methyleneblue (DMMB) assay.
      The changes of Sox9 mRNA and protein levels via TGF-beta1 were detected by RT-PCR
      and Western blot analysis in each. RESULTS: The amount of sGAG was increased with
      the lapse of time during incubation, and sGAG content of pellet cultured cells
      was much larger than monolayer culture. When primary cultured intervertebral disc
      cells in monolayer and pellet cultures were treated by TGF-beta1 20 ng, sGAG
      content of experimental group was increased significantly compared to control
      group in both cultures. L-Ascorbic acid of serial concentrations (50-300 ug/ml)
      increased sGAG content of mono layer cultured intervertebral disc cells
      significantly in statistics. The co-treatment of TGF-beta1 and L-ascorbic acid
      increased more sGAG production than respective treatment. After treating with TGF
      beta1, Sox9 mRNA and protein expression rates were significantly increased in
      disc cells compared with the control group. CONCLUSION: This study suggests that
      TGF-beta1 would increase sulfated glycosaminoglycan (sGAG) and other
      proteoglycans such as versican by elevating Sox9 mRNA and protein expressions in
      order.

PMID- 19096624
TI  - An Unusual Case of a Thrombosed Giant Distal PICA Aneurysm Simulating a Large
      Cavernous Angioma.
AB  - A 64-year-old woman was referred to our hospital with a one-month history of
      progressive headache. Magnetic resonance imaging (MRI) showed a hemorrhagic mass
      adjacent to the left inferior cerebellar hemisphere associated with a peripheral
      rim of signal void. Angiography demonstrated an avascular mass and the
      provisional diagnosis was a large cavernous angioma in the cerebellum.
      Intraoperative findings revealed a thrombosed giant aneurysm of the left distal
      posterior inferior cerebellar artery (PICA). We report an unusual case of a
      completely thrombosed giant aneurysm simulating a large cavernous angioma in the
      cerebellum. The cerebellar cisternal location of the mass may be a clue for the
      pre-operative diagnosis of an aneurysm.

PMID- 19096625
TI  - Hydrothorax due to migration of ventriculoperitoneal shunt catheter.
AB  - A cerebrospinal fluid hydrothorax is a very rare complication following
      ventriculoperitoneal (VP) shunt and usually reported in children. We report a
      case of 47-year-old woman who developed massive hydrothorax and respiratory
      distress following intrathoracic migration of distal shunt catheter. After the
      confirmation of catheter in thoracic cavity using radionuclide shuntogram, the
      patient was successfully treated with laparoscopic shunt catheter reposition.

PMID- 19096626
TI  - Contralateral intraparenchymal hemorrhage following aneurysmal clipping.
AB  - Post-clipping intraparenchymal hemorrhage of the contralateral hemisphere is a
      very unusual phenomenon in a patient with aneurysmal subarachnoid hemorrhage,
      unless there is an underlying condition. We report a complicated case of 47-year
      old man, who underwent uneventful clipping of ruptured aneurysm and experienced
      vasospasm two weeks later. Vasospasm was treated by intra-arterial nimodipine and
      systemic hyperdynamic therapy. One week thereafter, he became unconscious due to
      intraparenchymal hemorrhage on the anterior border-zone of contalateral
      hemisphere, but intraoperative and pathologic findings failed to disclose any
      vascular anomaly. We suggest that the anti-spastic regimens cause local
      hemodynamic redistribution through the vasodilatory effect and in turn, resulted
      in such an unexpected bleeding.

PMID- 19096627
TI  - Cerebellar ganglioglioma.
AB  - The location of ganglioglioma (GG) within the infratentorial compartment is
      unusual. The authors report a rare case of GG in the cerebellar hemisphere. A 12
      year-old boy suffered from headache and gait disturbance. Neuroimaging studies
      demonstrated a large enhancing cerebellar mass with cystic components compressing
      the forth ventricle. After complete resection of the tumor, the patient became
      symptom free. Histological examination on the tumor disclosed glial cells and
      dysplastic ganglion cells. Although it is a rare tumor, in the appropriate
      clinical setting, a GG should be considered in the presence of a cerebellar mass
      with both solid and cystic components on magnetic resonance images in children.

PMID- 19096628
TI  - Giant Lymph Node Hyperplasia (Castleman's Disease) as a Rare Cause of Back Pain.
AB  - Giant lymph node hyperplasia (Castleman's disease) is a nonneoplastic
      lymphoproliferative disorder of unknown etiology that usually occurs in the
      chest. Its morphological recognition is based on a composition of various
      histological features. The mass is often asymptomatic, but it can cause
      nonspecific thoracic symptoms, such as regional pain. This disease can be found
      wherever lymph nodes are present, but two-thirds of these tumors are found in the
      chest, along the tracheobronchial tree in the mediastinum or lung hilus. However,
      we experienced an unusual case of Castleman's disease as a cause of back pain
      that was localized in the posterior mediastinum bordering the chest wall.

PMID- 19096629
TI  - Post-laminectomy kyphosis in patients with cervical ossification of the posterior
      longitudinal ligament : does it cause neurological deterioration?
AB  - OBJECTIVE: Total laminectomy (TL) is an effective surgical technique for the
      treatment of cervical ossification of the posterior longitudinal ligament (OPLL)
      along multiple levels. However, kyphosis and probable neurological deterioration
      have been frequently reported after laminectomy. We analyzed the changes in the
      cervical curvature after TL and subsequent changes in neurological status.
      METHODS: We retrospectively reviewed the records of 14 patients who underwent TL
      for the treatment of cervical OPLL between Jan. 1998 and Dec. 2003. TL was
      selected according to the previously determined criteria. The curvature of the
      cervical spine was visualized on a lateral cervical spine X-ray and measured
      using Ishihara's Curvature Index (CI) before the operation and at the last follow
      up examination. Perioperative neurological status was estimated using the
      modified Japanese Orthopedic Association score and the Improvement Rate (IR) at
      the same time as the images were evaluated. RESULTS: The mean age of the patients
      was 57 years, the male/female ratio was 10:4, and the mean follow-up period was
      41 months. The mean number of OPLL was 4.9, and the mean number of operated
      levels was also 4.9. The CI decreased after TL (p=0.002), which was indicative of
      a kyphotic change. However, this kyphotic change showed no correlation with the
      length of the follow-up period, number of operated levels and preoperative CI.
      Neurological examination at the last follow-up showed an improved neurological
      status in all patients (p=0.001). There was no neurological deterioration in any
      case during the follow-up period. Moreover, there was no correlation between IR
      and the degree of kyphotic change. Postoperative complications, such as C5
      radiculopathy and epidural bleeding, resolved spontaneously without neurological
      sequelae. CONCLUSION: Kyphotic change was observed in all but one patient who
      underwent TL for the treatment of cervical OPLL. However, we did not find any
      contributing factors to kyphosis or evidence of postoperative neurological
      deterioration.

PMID- 19096630
TI  - Retrospective analysis on 76 cases of cerebral arteriovenous malformations
      treated by gamma knife radiosurgery.
AB  - OBJECTIVE: Outcome of gamma knife radiosurgery (GKS) in the consecutive 100 cases
      with cerebral arteriovenous malformations (AVMs) was analyzed. METHODS: Data from
      initial 100 patients treated with GKS in the authors' institute were reviewed
      retrospectively. Spetzler-Martin grade at diagnosis were I in 18 patients, II in
      27, III in 36, IV in 11, and V in 8. Thirty-five patients had experienced
      previous bleeding, 27 patients presented with seizure, and 31 patients presented
      with headache. The mean volume of the lesion was 4.3 cm(3) (0.1-29.3 cm(3)). The
      median radiation dose delivered to the margin was 20.0 Gy (13-32 Gy). Mean follow
      up period was 37.5 months (5-63 months). RESULTS: Angiographic follow-up was
      performed in 48 patients at least 2 years after GKS. Sixteen patients were lost
      in follow up following 2 years from GKS. Twenty-eight of 48 patients (58%) showed
      complete obliteration and 20 patients (42%) showed partial obliteration. Seven
      patients presented with post-GKS hemorrhage. Adverse radiation effect (ARE) was
      observed at follow-up MRI in 25 of 76 patients, and it was symptomatic in 5
      patients. Complete obliteration was confirmed in 24 of 31 (77%) patients with
      volume less than 4 cm(3), meanwhile only 4 of 17 (24%) patients with volume of 4
      cm(3) or more showed complete obliteration. Complete obliteration rate was 67%
      with 20 Gy or higher marginal dose, 63% with 15-20 Gy, and 17% with less than 15
      Gy. CONCLUSION: GKS can provide high rates of obliteration with acceptable risk
      of morbidity in a subgroup of small AVMs. However, overall outcome in whole
      spectrum of AVMs, in which large proportion of cases have unfavorable
      characteristics for radiosurgery, is much worse. More effective therapeutic
      strategy needs to be developed for large AVMs that are difficult to be managed
      with current available treatment modalities.

PMID- 19096631
TI  - The merits of endovascular coil surgery for patients with unruptured intracranial
      aneurysms.
AB  - OBJECTIVE: The purpose of this study was to report the morbidity, mortality,
      angiographic results, and merits of elective coiling of unruptured intracranial
      aneurysms. METHODS: Ninety-six unruptured aneurysms in 92 patients were
      electively treated with detachable coils. Eighty-one of these aneurysms were
      located in the anterior circulation, and 15 were located in the posterior
      circulation. Thirty-six aneurysms were treated in the presence of previously
      ruptured aneurysms that had already undergone operation. Nine unruptured
      aneurysms presented with symptoms of mass effect. The remaining 51 aneurysms were
      incidentally discovered in patients with other cerebral diseases and in
      individuals undergoing routine health maintenance. Angiographic and clinical
      outcomes and procedure-related complications were analyzed. RESULTS: Eight
      procedure-related untoward events (8.3%) occurred during surgery or within
      procedure-related hospitalization, including thromboembolism, sac perforation,
      and coil migration. Permanent procedural morbidity was 2.2% ; there was no
      mortality. Complete occlusion was achieved in 73 (76%) aneurysms, neck remnant
      occlusion in 18 (18.7%) aneurysms, and incomplete occlusion in five (5.2%)
      aneurysms. Recanalization occurred in 8 (15.4%) of 52 coiled aneurysms that were
      available for follow-up conventional angiography or magnetic resonance
      angiography over a mean period of 13.3 months. No ruptures occurred during the
      follow-up period (12-79 months). CONCLUSION: Endovascular coil surgery for
      patients with unruptured intracranial aneurysms is characterized by low
      procedural mortality and morbidity and has advantages in patients with poor
      general health, cerebral infarction, posterior circulation aneurysms, aneurysms
      of the proximal internal cerebral artery, and unruptured aneurysms associated
      with ruptured aneurysm. For the management of unruptured aneurysms, endovascular
      coil surgery is considered an attractive alterative option.

PMID- 19096632
TI  - Thromboembolic Events after Coil Embolization of Cerebral Aneurysms : Prospective
      Study with Diffusion-Weighted Magnetic Resonance Imaging Follow-up.
AB  - OBJECTIVE: In order to assess the incidence of thromboembolic events and their
      clinical presentations, the present study prospectively examined routine brain
      magnetic resonance images (MRI) taken within 48 hours after a coil embolization
      of cerebral aneurysms. METHODS: From January 2006 to January 2008, 163 cases of
      coil embolization of cerebral aneurysm were performed along with routine brain
      MRI, including diffusion-weighted magnetic resonance (DW-MR) imaging, within 48
      hours after the embolization of the aneurysm to detect the silent thromboembolic
      events regardless of any neurological changes. If any neurological changes were
      observed, an immediate brain MRI follow-up was performed. High-signal-intensity
      lesions in the DW-MR images were considered as acute thromboembolic events and
      the number and locations of the lesions were also recorded. RESULTS: Among the
      163 coil embolization cases, 98 (60.1%) showed high-signal intensities in the DW
      MR imaging follow-up, 66 cases (67.0%) involved the eloquent area and only 6
      cases (6.0%) showed focal neurological symptoms correlated to the DW-MR findings.
      The incidence of DW-MR lesions was higher in older patients (>/=60 yrs) when
      compared to younger patients (<60 yrs) (p=0.002, odd's ratio=1.043). The older
      patients also showed a higher incidence of abnormal DW-MR signals in aneurysm
      unrelated lesions (p=0.0003, odd's ratio=5.078). CONCLUSION: The incidence of
      symptomatic thromboembolic attacks after coil embolization of the cerebral
      aneurysm was found to be lower than that reported in previous studies. While DW
      MR imaging revealed a higher number of thromboembolic events, most of these were
      clinically silent and transient and showed favorable clinical outcomes. However,
      the incidence of DW-MR abnormalities was higher in older patients, along with
      unpredictable thromboembolic events on DW-MR images. Thus, in order to provide
      adequate and timely treatment and to minimize neurological sequelae, a routine DW
      MR follow-up after coil embolization of cerebral aneurysms might be helpful,
      especially in older patients.

PMID- 19096633
TI  - The Utility and Benefits of External Lumbar CSF Drainage after Endovascular
      Coiling on Aneurysmal Subarachnoid Hemorrhage.
AB  - OBJECTIVE: Cerebral vasospasm still remains a major cause of the morbidity and
      mortality, despite the developments in treatment of aneurysmal subarachnoid
      hemorrhage. The authors measured the utility and benefits of external lumbar
      cerebrospinal fluid (CSF) drainage to prevent the clinical vasospasm and its
      sequelae after endovascular coiling on aneurysmal subarachnoid hemorrhage in this
      randomized study. METHODS: Between January 2004 and March 2006, 280 patients with
      aneurysmal subarachnoid hemorrhage were treated at our institution. Among them,
      107 patients met our study criteria. The treatment group consisted of 47 patients
      who underwent lumbar CSF drainage during vasospasm risk period (about for 14 days
      after SAH), whereas the control group consisted of 60 patients who received the
      management according to conventional protocol without lumbar CSF drainage. We
      created our new modified Fisher grade on the basis of initial brain computed
      tomography (CT) scan at admission. The authors established five outcome criteria
      as follows : 1) clinical vasospasm; 2) GOS score at 1-month to 6-month follow-up;
      3) shunt procedures for hydrocephalus; 4) the duration of stay in the ICU and
      total hospital stay; 5) mortality rate. RESULTS: The incidence of clinical
      vasospasm in the lumbar drain group showed 23.4% compared with 63.3% of
      individuals in the control group. Moreover, the risk of death in the lumbar drain
      group showed 2.1% compared with 15% of individuals in the control group. Within
      individual modified Fisher grade, there were similar favorable results. Also,
      lumbar drain group had twice more patients than the control group in good GOS
      score of 5. However, there were no statistical significances in mean hospital
      stay and shunt procedures between the two groups. IVH was an important factor for
      delayed hydrocephalus regardless of lumbar drain. CONCLUSION: Lumbar CSF drainage
      remains to play a prominent role to prevent clinical vasospasm and its sequelae
      after endovascular coiling on aneurysmal subarachnoid hemorrhage. Also, this
      technique shows favorable effects on numerous neurological outcomes and
      prognosis. The results of this study warrant clinical trials after endovascular
      treatment in patients with aneurysmal SAH.

PMID- 19096635
TI  - Surgical treatments for cervical spondylotic myelopathy associated with athetoid
      cerebral palsy.
AB  - OBJECTIVE: To evaluate the clinical characteristics and surgical outcomes of the
      patients with cervical spondylotic myelopathy associated with athetoid cerebral
      palsy. METHODS: The authors reviewed the clinical and neurodiagnostic findings,
      surgical managements and outcomes in six consecutive patients with cervical
      spondylotic myelopathy associated with athetoid cerebral palsy who had been
      treated with surgical decompression and fusion procedures between January 1999
      and December 2005. The mean age of the 6 patients (four women and two men) at the
      time of surgery was 42.8 years (range, 31-55 years). The mean follow-up period
      was 56.5 months (range, 17-112 months). The neurological outcome was evaluated
      before and after operations (immediately, 6 months after and final follow-up)
      using grading systems of the walking ability, brachialgia and deltoid power.
      RESULTS: At immediate postoperative period, after 6 months, and at final follow
      up, all patients showed apparent clinical improvements in walking ability, upper
      extremity pain and deltoid muscle strength. Late neurological deterioration was
      not seen during follow-up periods. There were no serious complications related to
      surgery. CONCLUSION: Surgical decompression and stabilization in patients with
      cervical spondylotic myelopathy associated with athetoid cerebral palsy have been
      challenging procedure up to now. Our results indicate that early diagnosis and
      appropriate surgical procedure can effectively improve the clinical symptoms and
      neurological function in patients with cervical spondylotic myelopathy and
      athetoid cerebral palsy, even in those with severe involuntary movements.

PMID- 19096634
TI  - The Patterns of Intraosseous Venography before Percutaneous Vertebroplasty for
      Osteoporotic Compression Fractures.
AB  - OBJECTIVE: Bone cement leakage is a well-known potential complication of
      percutaneous vertebroplasty (PVP) in patients with osteoporotic compression
      fracture. Even though there has been a controversy in the efficacy of antecedent
      venography to prevent this complication, many authors have performed intraosseous
      venography before bone cement injection. The goal of this study was to classify
      the venous drainage patterns of spine before PVP, and compare their patterns at
      different vertebral levels. METHODS: The authors retrospectively reviewed 1,042
      intraosseous venographic patterns in 321 patients with 574 osteoporotic
      compression fractures during six-year period in one institution. To classify
      venogram patterns, we selected simple lateral X-ray of spine taken immediately
      after injection of the contrast dye. We classified the venography patterns
      according to contrast leakage pattern and leakage direction as follows;
      trabecular (TR), trabecular anterior (TA), trabecular posterior (TP), trabecular
      anterior-posterior (TAP), trabecular lateral (TL), venous anterior(VA), venous
      posterior (VP), venous anterior-posterior (VAP), soft tissue (ST). Also, we
      compared venogram patterns according to different spinal levels. RESULTS: In
      overall, the most common pattern was TP type accounting for 37.4% (390/1042) of
      all intraosseous venograms. This is followed by TAP in 21.5%, TR 17.4%, TA 11.6%,
      TL 5.8%, ST 4.1%, VA 1.2%, VP 0.6%, and VAP 0.4% in descending order of
      frequency. According to the spinal level, TR and TAP types were most common in
      thoracic spine (T6-T10), TP type was most common in thoraco-lumbar spine (T11
      L2), and TP and TAP types were most common in lumbo-sacral spine (L3-S1).
      Contrast dye leakage to soft tissue such as psoas muscle or disc were detected in
      43 (4.1%) venograms. Direct venous drainage without staining of vertebral body
      was found in 23 (2.2%) venograms. The 8.3% of thoracic venogram showed direct
      venous drainage. Thoracic level showed a more tendency of direct venous drainage
      than other spine levels (p<0.01). CONCLUSION: The authors propose a new
      classification system of intraosseous venography during PVP. The trabecular
      posterior (TP) type is most common through all spine, and venous-filling (V) type
      was most frequent in thoracic spine. Further study would be necessary to
      elucidate the efficacy of this classification system to prevent bone cement
      leakage during PVP.

PMID- 19096636
TI  - Delayed cerebral abscess as a shunt complication and endoscopic removal of the
      ventricular catheter and abscess.
AB  - Shunt infections are a common complication of ventriculoperitoneal (VP) shunts,
      but the formation of a brain abscess related to a shunt system is very rare. A 44
      year-old woman had a VP shunt inserted for hydrocephalus secondary to a
      subarachnoid hemorrhage. She suffered an episode of meningitis and sepsis 8
      months after the shunt operation. After recovering from the meningitis, she
      complained of a loss of cognitive function. An enhancing mass was found in the
      frontal lobe, around the frontal horn of the lateral ventricle, and the
      ventricular catheter was embedded inside the mass. The ventricular catheter and
      cerebral abscess were removed using neuroendoscopy. We present an interesting
      case of a shunt-related brain abscess which illustrates the usefulness of
      neuroendoscopy.

PMID- 19096637
TI  - Eosinophilic granuloma presenting as an epidural hematoma and cyst.
AB  - Langerhans' cell histiocytosis (LCH) is a rare immunologic disorder characterized
      by histiocyte proliferation in multiple organ systems. Eosinophilic granuloma, a
      benign bone lesion, represents a focal form of LCH. We experienced a case of
      Langerhans' cell histiocytosis in a patient who presented with intracranial
      epidural hematoma and cyst on the midline of the frontal skull. A 10-year-old boy
      presented with a rapidly growing large scalp mass on the midline frontal area
      after mild head trauma. The scalp mass was painless and immobile. Plain skull x
      ray showed a punched-out bone lesion. Computed tomography and magnetic resonance
      imaging showed a non-enhancing osteolytic lesion presenting with an epidural
      hematoma and cyst on the midline of the frontal skull. The lesion of the skull
      was completely resected and the patient's recovery was uneventful. The acute
      presentation of a solitary eosinophilic granuloma of skull with an epidural
      hematoma has been described in only five cases in the literature and we report
      the first case of LCH presenting as an intracranial epidural hematoma on frontal
      area.

PMID- 19096638
TI  - Linezolid Treatment for Osteomyelitis due to Staphylococcus Epidermidis with
      Reduced Vancomycin Susceptibility.
AB  - Limited therapeutic options are available for vancomycin intermediate-resistant
      Staphylococcus Epidermidis (VISE) infections and no optimum therapy has been
      established. We report a case of VISE skull osteomyelitis that was successfully
      treated with linezolid. The patient was a 53-year-old man who presented with
      headache, nausea and dysphasia. Brain computerized tomography (CT) demonstrated a
      subdural hematoma in the left hemisphere. Craniotomy and hematoma evacuation was
      performed and he showed good recovery despite a scalp wound infection caused by
      methicillin-resistant Staphylococcus aureus (MRSA). The organism isolated from
      the scalp wound was sensitive to vancomycin. The patient was treated with
      intravenous vancomycin for 44 days. However, he showed a high fever, persistent
      positive methicillin-resistant Staphylococcus Epidermidis (MRSE) blood cultures,
      and a deteriorating clinical status. He underwent infected skull bone flap
      removal and linezolid treatment for 35 days. During one year of follow up, he has
      not had any further episodes of osteomyelitis or fever. Linezolid has shown to be
      effective agent to eradiate osteomyelitis caused by VISE.

PMID- 19096639
TI  - Predisposing factors related to shunt-dependent chronic hydrocephalus after
      aneurysmal subarachnoid hemorrhage.
AB  - OBJECTIVE: Hydrocephalus is a common sequelae of aneurysmal subarachnoid
      hemorrhage (SAH) and patients who develop hydrocephalus after SAH typically have
      a worse prognosis than those who do not. This study was designed to identify
      factors predictive of shunt-dependent chronic hydrocephalus among patients with
      aneurysmal SAH, and patients who require permanent cerebrospinal fluid diversion.
      METHODS: Seven-hundred-and-thirty-four patients with aneurysmal SAH who were
      treated surgically between 1990 and 2006 were retrospectively studied. Three
      stages of hydrocephalus have been categorized in this paper, i.e., acute (0-3
      days after SAH), subacute (4-13 days after SAH), chronic (>/=14 days after SAH).
      Criteria indicating the occurrence of hydrocephalus were the presence of
      significantly enlarged temporal horns or ratio of frontal horn to maximal
      biparietal diameter more than 30% in computerized tomography. RESULTS: Overall,
      66 of the 734 patients (8.9%) underwent shunting procedures for the treatment of
      chronic hydrocephalus. Statistically significant associations among the following
      factors and shunt-dependent chronic hydrocephalus were observed. (1) Increased
      age (p < 0.05), (2) poor Hunt and Hess grade at admission (p < 0.05), (3)
      intraventricular hemorrhage (p < 0.05), (4) Fisher grade III, IV at admission (p
      < 0.05), (5) radiological hydrocephalus at admission (p < 0.05), and (6) post
      surgery meningitis (p < 0.05) did affect development of chronic hydrocephalus.
      However the presence of intracerebral hemorrhage, multiple aneurysms, vasospasm,
      and gender did not influence on the development of shunt-dependent chronic
      hydrocephalus. In addition, the location of the ruptured aneurysms in posterior
      cerebral circulation did not correlate with the development of shunt-dependent
      chronic hydrocephalus. CONCLUSION: Hydrocephalus after aneurysmal SAH seems to
      have a multifactorial etiology. Understanding predisposing factors related to the
      shunt-dependent chronic hydrocephalus may help to guide neurosurgeons for better
      treatment outcomes.

PMID- 19096640
TI  - Long term results of microsurgical dorsal root entry zonotomy for upper extremity
      spasticity.
AB  - OBJECTIVE: The purpose of the present study is to assess the long-term results of
      microsurgical dorsal root entry zonotomy (MDT) for the treatment of medically
      intractable upper-extremity spasticity. METHODS: The records of nine adult
      patients who underwent MDT by one operating neurosurgeon from March 1999 to June
      2004 were retrospectively reviewed by another investigator who had no role in the
      management of these patients. In all patients, MDT was performed on all roots of
      the upper limb (from C5 to T1) for spasticity of the upper extremity. The degree
      of spasticity was measured by the Modified Ashworth Scale (grade 0-4). Severity
      of the pain level was determined using the Numeric Rating Scale (NRS, score 0
      10). Also, patient satisfaction of the post-operative outcome was assessed.
      RESULTS: Comparing the preoperative and postoperative spasticity using the
      Modified Ashworth Scale, we observed improvement in all patients, particularly in
      five of the nine patients (55.6%) who improved by three grades over an average of
      66.4 months (range, 40-96). Regarding patient satisfaction, seven patients
      (77.8%) had affirmative results. None of the patients experienced severe, life
      threatening, postoperative complications. We observed a decrease in the intensity
      of painful spasms to less than three scores as measured by NRS in all four
      patients with associated pain. CONCLUSION: This study shows that MDT provides
      significant, long-term reduction of harmful spasticity and associated pain in the
      upper limbs.

PMID- 19096641
TI  - Percutaneous balloon compression of trigeminal ganglion for the treatment of
      idiopathic trigeminal neuralgia : experience in 50 patients.
AB  - OBJECTIVE: We assessed the surgical results of percutaneous balloon compression
      in 50 patients with idiopathic trigeminal neuralgia. METHODS: Fifty patients with
      follow-up period of more than 12 months were retrospectively analyzed. The mean
      follow-up period was 42 months (range, 12-82). The mean age was 65.8 years
      (range, 27-83). Seventeen patients (34%) had other previous surgical procedures.
      The balloon was inflated by injecting radio-contrast media under brief general
      anesthesia according to Mullan's technique. The mean inflating time was 88
      seconds (range, 60-120). The whole procedure took about 20 minutes. RESULTS: We
      reported excellent and good results in 70% of the cases, poor in 6% as annoying
      dysesthesia, recurrence in 16%, and 8% failure due to technical deficiencies.
      Forty-six patients (92%) were initially relieved of their pain. There were
      permanent motor weakness of the masseter muscle in 4% of patients and transitory
      diplopia in 8%. Neither anesthesia dolorosa nor keratitis occurred. Almost all
      patients (92%) were discharged postoperatively within two days. CONCLUSION: These
      results indicate that balloon compression would be an effective method with
      acceptable morbidity, technically, it can be performed rapidly and simply in the
      treatment of idiopathic trigeminal neuralgia.

PMID- 19096642
TI  - Expression of cancer-testis genes in brain tumors.
AB  - OBJECTIVE: Cancer-testis (CT) genes are considered promising candidates for
      immunotherapeutic approaches. The aim of this study was to investigate which CT
      genes should be targeted in immunotherapy for brain tumors. METHODS: We
      investigated the expression of 6 CT genes (MAGE-E1, SOX-6, SCP-1, SSX-2, SSX-4,
      and HOM-TES-85) using reverse-transcription polymerase chain reaction in 26
      meningiomas and 32 other various brain tumor specimens, obtained from the
      patients during tumor surgery from 2000 to 2005. RESULTS: The most frequently
      expressed CT genes of meningiomas were MAGE-E1, which were found in 22/26 (85%)
      meningioma samples, followed by SOX-6 (9/26 or 35%). Glioblastomas were most
      frequently expressed SOX-6 (6/7 or 86%), MAGE-E1 (5/7 or 71%), followed by SSX-2
      (2/7 or 29%) and SCP-1 (1/7 or 14%). However, 4 astrocytomas, 3 anaplastic
      astrocytomas, and 3 oligodendroglial tumors only expressed MAGE-E1 and SOX-6.
      Schwannomas also expressed SOX-6 (5/6 or 83%), MAGE-E1 (4/6 or 67%), and SCP-1
      (2/6 or 33%). CONCLUSION: The data presented here suggest that MAGE-E1 and SOX-6
      genes are expressed in a high percentage of human central nervous system tumors,
      which implies the CT genes could be the potential targets of immunotherapy for
      human central nervous system tumors.

PMID- 19096643
TI  - Cerebellar glioblastoma multiforme in an adult.
AB  - Primary cerebellar glioblastoma multiforme (GBM) is a rare tumor in adults that
      accounts for just 1% of all cases of GBM. Due to their rarity, cerebellar GBMs
      are not yet completely understood about the pathogenesis and the prognosis. Here,
      we present a case of GBM in a 69-year-old man. Neurologic examination revealed
      the presence of cerebellar signs. Magnetic resonance imaging (MRI) showed a 4.5 x
      3.6 cm-sized, ill-defined, heterogeneously enhancing mass in the left cerebellum
      and two patchy hyperintense lesions in the right cerebellum with minimal
      enhancement. After operation, glioblastoma was histologically confirmed.
      Postoperative radiotherapy with concomitant and adjuvant temozolomide
      chemotherapy was subsequently followed. Here, a case of unusual GBM in the
      cerebellum is reported with review of literature regarding the pathogenesis, the
      differential diagnosis and prognosis. There was no evidence of recurrence during
      postoperative one year. This patient showed a good prognosis in spite of the
      multiple lesions.

PMID- 19096644
TI  - Giant cavernous malformation : a case report and review of the literature.
AB  - Giant cavernous malformations (GCMs) occur very rarely and little has been
      reported about their clinical characteristics. The authors present a case of a 20
      year-old woman with a GCM. She was referred due to two episodes of generalized
      seizure. Computed tomography and magnetic resonance image demonstrated a
      heterogeneous multi-cystic lesion of 7 x 5 x 5 cm size in the left frontal lobe
      and basal ganglia, and enhancing vascular structure abutting medial portion of
      the mass. These fingings suggested a diagnosis of GCM accompanying venous
      angioma. After left frontal craniotomy, transcortical approach was done. Total
      removal was accomplished and the postoperative course was uneventful. GCMs do not
      seem differ clinically, surgically or histopathologically from small cavernous
      angiomas, but imaging appearance of GCMs may be variable. The clinical,
      radiological feature and management of GCMs are described based on pertinent
      literature review.

PMID- 19096645
TI  - Intracranial invasion from recurrent angiosarcoma of the scalp.
AB  - Angiosarcoma of the brain, either primary or metastatic is extremely rare.
      Moreover, angiosarcoma metastasizing to the brain is also highly unlike to occur
      comparing with metastases to the other organs. Thus, an ideal treatment strategy
      has not been established. A 67-year-old man with past surgical history of a scalp
      angiosarcoma underwent surgical resection of intracranial invasion. Because of
      wide scalp flap excision and resultant poor vascularity of the scalp flap,
      additional radiation was not provided. Because adjuvant therapy is impossible due
      to poor scalp condition, more careful but ample resection of the primary lesion
      is essential to conduct initial operation.

PMID- 19096646
TI  - A Cerebral Astroblastoma Mimicking an Extra-axial Neoplasm.
AB  - Astroblastoma is a rarely diagnosed primary brain neoplasm whose histogenesis has
      been clarified recently. It occurs in children and young adults and presents as a
      well circumscribed, contrast-enhancing lesion in the cerebral hemisphere. We
      present a case of 20-year-old woman with an astroblastoma in the left temporal
      convexity that was treated with total tumor resection alone. We thought the mass
      was extra-axial neoplasm based on radiological findings of computed tomography
      and magnetic resonance imaging initially, but later, we obtained angiographic
      findings suggesting an intra-axial neoplasm. The patient is doing well even two
      years after surgery. The characteristic radiological and histopathological
      features of this case are described with a literature review. An astroblastoma
      should be included in the differential diagnosis of a superficially located tumor
      presenting with the findings of an extra-axial mass, especially in a young
      patient.

PMID- 19096647
TI  - Traumatic Pseudoaneurysm of the Superficial Temporal Artery Diagnosed by 3
      dimensional CT Angiography.
AB  - Pseudoaneurysm arising from the superficial temporal artery (STA) is a rare and
      potentially critical cause of palpable mass. Most pseudoaneurysms form as a
      result of blunt trauma and present as painless, pulsatile mass that may be
      associated with pathologic finding and enlarged size. We report a rare case of
      pseudoaneurysm arising from STA caused by blunt injury and diagnosed by 3
      dimensional computed tomography (CT) angiography.

PMID- 19096648
TI  - Delayed bone cement displacement following balloon kyphoplasty.
AB  - We report a rare case of delayed cement displacement after balloon kyphoplasty in
      patient with Kummell's desease. A 78-year-old woman with Kummell's desease at T12
      level received percutaneous balloon kyphoplasty. Two months after surgery, the
      patient complained of progressive severe back pain. Computed tomographic scans
      revealed a breakdown of the anterior cortex and anterior displacement of bone
      cement. Although this complication is very rare, it is likely to occur in
      treatment of Kummell's desease accompanying anterior cortical defect.

PMID- 19096649
TI  - Open Surgical Evacuation of Spontaneous Putaminal Hematomas: Prognostic Factors
      and Comparison of Outcomes between Transsylvian and Transcortical Approaches.
AB  - OBJECTIVE: The purpose of this study was to investigate the factors affecting the
      surgical outcome and to compare the surgical results between transsylvian and
      transcortical approaches in patients with putaminal hematomas. METHODS:
      Retrospective review of charts and CT scan images was conducted in 45 patients
      (20 transsylvian and 25 transcortical approaches) who underwent open surgical
      evacuation of putaminal hematomas. Mean Glasgow coma scale (GCS) score and
      hematoma volume were 7.5+/-3.2 and 78.1+/-29.3 cc, respectively. The factors
      affecting the functional mortality were investigated using a multivariate
      logistic regression analysis. In addition, surgical results between transsylvian
      and transcortical approaches were compared. RESULTS: None of the patients had a
      good recovery after the surgery. Overall functional survival rate and mortality
      were 37.7% and 31%, respectively. The only risk factor for functional mortality
      was GCS motor score after controlling age, history of hypertension, side of
      hematoma, hematoma amount, midline shift, presence of intraventricular hemorrhage
      and surgical approach (p=0.005). Even though a transcortical approach was shorter
      in operative time (4.4 versus 5.1 hour) and showed a higher mortality rate (40%
      versus 20%) and lower functional survival (45% versus 35%) compared to the
      transsylvian approach, the differences were not statistically significant between
      the two groups. CONCLUSION: In patients who have large amounts of hematoma and
      require open surgical evacuation, the only significant risk factor for functional
      survival is the preoperative GCS score. Cortical incision methods such as
      transsylvian and transcortical approaches have no influence on the surgical
      outcome. To decompress the swollen brain rapidly, transcortical approach seems to
      be more suitable than transsylvian approach.

PMID- 19096650
TI  - Bone cement augmentation of short segment fixation for unstable burst fracture in
      severe osteoporosis.
AB  - OBJECTIVE: The purpose of this study was to determine the efficacy of short
      segment fixation following postural reduction for the re-expansion and
      stabilization of unstable burst fractures in patients with osteoporosis. METHODS:
      Twenty patients underwent short segment fixation following postural reduction
      using a soft roll at the involved vertebra in cases of severely collapsed
      vertebrae of more than half their original height. All patients had unstable
      burst fracture with canal compromise, but their motor power was intact. The
      surgical procedure included postural reduction for 2 days and bone cement
      augmented pedicle screw fixations at one level above, one level below and the
      fractured level itself. Imaging and clinical findings, including the level of the
      vertebra involved, vertebral height restoration, injected cement volume, local
      kyphosis, clinical outcome and complications were analyzed. RESULTS: The mean
      follow-up period was 15 months. The mean pain score (visual analogue scale) prior
      to surgery was 8.1, which decreased to 2.8 at 7 days after surgery. The kyphotic
      angle improved significantly from 21.6+/-5.8 degrees before surgery to 5.2+/-3.7
      degrees after surgery. The fraction of the height of the vertebra increased from
      35% and 40% to 70% in the anterior and middle portion. There were no signs of
      hardware pull-out, cement leakage into the spinal canal or aggravation of
      kyphotic deformities. CONCLUSION: In the management of unstable burst fracture in
      patients with severe osteoporosis, short segment pedicle screw fixation with bone
      cement augmentation following postural reduction can be used to reduce the total
      levels of pedicle screw fixation and to correct kyphotic deformities.

PMID- 19096651
TI  - Computerized tomographic measurements of morphometric parameters of the c2 for
      the feasibility of laminar screw fixation in korean population.
AB  - OBJECTIVE: C2 laminar screw fixation is considered as an excellent alternative to
      Magerl's transfacetal approach or Harms construct for the atlantoaxial
      stabilization. However, to our knowledge, there is no report on the feasibility
      of the new approach to Korean population. We investigated morphometric parameters
      of the dorsal arch of the C2 to provide the quantitative data for the feasibility
      of laminar screw fixation. METHODS: One-hundred-and-two patients' cervical
      computed tomography had been reconstructed and investigated on the anatomical
      parameters related with C2 laminar screw placement. Sixty patients were male and
      forty-two patients were female. Measurements included the laminar thickness and
      slope, spino-laminar angle, and maximal screw length. RESULTS: Ages ranged from
      20 to 81 and the mean age was 48.4. Mean laminar thickness was 5.7 mm (+/-1.0)
      (5.8 mm in male and 5.4 mm in female). Fifty-one patients (50%) had a laminar
      thickness smaller than 5.5 mm at least unilaterally, therefore the patients were
      considered as inappropriate candidates for the laminar screw fixation in the
      smaller side of the laminae. Mean value of maximal length of screw was 33.3 mm
      (34.3 mm in male and 31.9 mm in female). Mean spino-laminar angle was 43.2
      degrees and mean slope angle was 32.9 degrees . CONCLUSION: Half of patients had
      inappropriate laminar profiles to accommodate a 3.5 mm screw in at least one side
      of the axis. The three-dimensional computed tomography reconstruction is
      mandatory for the preoperative assessment for the feasibility of the C2 lamina.

PMID- 19096652
TI  - Microdecompression for extraforaminal L5-s1 disc herniation; the significance of
      concomitant foraminal disc herniation for postoperative leg pain.
AB  - OBJECTIVE: To analyze the relationship of concomitant foraminal lumbar disc
      herniation (FLDH) with postoperative leg pain after microdecompression for
      extraforaminal lumbar disc herniation (EFLDH) at the L5-S1 level. METHODS: Sixty
      five patients who underwent microdecompression for symptomatic EFLDH at the L5-S1
      level were enrolled. According to the severity of accompanying FLDH, EFLDH was
      classified into four categories (Class I : no FLDH; Class II : mild to moderate
      FLDH confined within a lateral foraminal zone; Class III : severe FLDH extending
      to a medial foraminal zone; Class IV : Class III with intracanalicular disc
      herniation). The incidence of postoperative leg pain, dysesthesia, analgesic
      medication, epidural block, and requirement for revision surgery due to leg pain
      were evaluated and compared at three months after initial surgery. RESULTS: The
      incidences of postoperative leg pain and dysesthesia were 36.9% and 26.1%,
      respectively. Pain medication and epidural block was performed on 40% and 41.5%,
      respectively. Revision surgery was recommended in six patients (9.2%) due to
      persistent leg pain. The incidences of leg pain, dysesthesia, and requirement for
      epidural block were higher in Class III/IV, compared with Class I/II. The
      incidence of requirement for analgesic medication was significantly higher in
      Class III/IV, compared with Class I/II (p=0.02, odds ratio=9.82). All patients
      who required revision surgery due to persistent leg pain were included in Class
      III/IV. CONCLUSION: Concomitant FLDH seems related to postoperative residual leg
      pain after microdecompression for EFLDH at the L5-S1 level.

PMID- 19096654
TI  - Multiple tuberculoma involving the brain and spinal cord in a patient with
      miliary pulmonary tuberculosis.
AB  - Although tuberculosis of the central nervous system is well known, the incidence
      of intramedullary tuberculomas is low and a combination of intramedullary with
      intracranial tuberculomas is extremely rare. We report a case of disseminated
      tuberculoma involving brain and spine with miliary pulmonary tuberculosis in a 66
      year-old woman initially presenting with fever, general weakness, back pain and
      motor weakness of both lower extremities. Despite medical therapy, she developed
      progressive motor weakness of both lower extremities with muscle strength 1/5 in
      both lower extremities. Urgent surgical intervention was followed and her muscle
      power and motor functions were improved gradually. The anti-tuberculous drugs
      were continued and the follow-up magnetic resonance imaging (MRI) of brain and
      spine showed that the lesions had become smaller or disappeared.

PMID- 19096653
TI  - STN DBS of Advanced Parkinson's Disease Experienced in a Specialized Monitoring
      Unit with a Prospective Protocol.
AB  - OBJECTIVE: In the evaluation of patients with Parkinson's disease (PD), most
      neurologists only see their patients during a limited period of their fluctuating
      24-hour-a-day lives. This study aimed to assess the short-term outcome of STN
      stimulation for patients with advanced PD evaluated in a 24-hour monitoring unit
      for movement disorder (MUMD) using a prospective protocol. METHODS: Forty-two
      patients with advanced PD consecutively treated with bilateral STN stimulation
      using multi-channel microelectrode recording were included in this study. All
      patients were evaluated using a 24-hour MUMD with a video recording/editing
      system and were evaluated with a prospective protocol of the Unified Parkinson's
      Disease Rating Scale, Hoehn and Yahr Staging, Schwab and England Activities of
      Daily Living, levodopa equivalent daily dose (LEDD), Short Form-36 Health Survey,
      and neuropsychological tests. Magnetic resonance (MR) images of the brain were
      performed prior to and six months after surgery. RESULTS: All patients were
      evaluated at three and six months after surgery. There was a rapid and
      significant improvement of the motor symptoms, especially in tremor and rigidity,
      after STN stimulation with low morbidity. Dyskinesia was markedly decreased with
      much lowered LEDD values by 50% after STN stimulation. 1.5T MR images were safely
      taken according to the manufacturer's guidelines at six months after surgery
      without any adverse effects in 41 patients treated with STN stimulations.
      CONCLUSION: Evaluations in a 24-hour monitoring unit could reduce the dose of
      medication efficiently to an optimal level with patients'comfort and improve the
      clinical symptoms in harmony with STN stimulation.

PMID- 19096655
TI  - Spontaneous spinal epidural hematoma.
AB  - Spontaneous spinal epidural hematoma (SSEH) is a relatively rare but significant
      spinal condition. Urgent surgical evacuation of a hematoma is generally indicated
      to prevent serious permanent neurological deficits. We encountered three cases of
      spontaneous spinal epidural hematomas associated with motor weakness that were
      treated successfully by surgical intervention.

PMID- 19096656
TI  - Fusiform intracanalicular ophthalmic artery aneurysm; case report and review of
      literature.
AB  - A 35-year-old man's vision had progressively deteriorated over a 3-month period.
      His left visual acuity was 5/20. Enhanced orbital computed tomographic (CT) scans
      revealed a fusiform dilatation of the ophthalmic artery in the left optic canal.
      Cerebral Angiography revealed a fusiform aneurysm on the left ophthalmic artery
      in the optic canal, measuring 6.2 x 4.6 mm in size. Four days after admission,
      visual acuity dropped to hand-motion. Endovascular treatment was chosen and a
      microcatheter was guided into the proximal segment of the ophthalmic artery.
      Using 4 detachable coils, parent artery occlusion was done. Three months after
      the intervention, the visual acuity in his left eye improved to 20/20. Dramatic
      recovery of visual acuity is exceptional with an ophthalmic artery trunk
      aneurysm. When an occlusion of the proximal ophthalmic artery is the only
      treatment option in such a situation, the endovascular occlusion of the proximal
      ophthalmic artery is quite feasible in the sense that it does not require any
      optic nerve manipulation.

PMID- 19096657
TI  - Spontaneous ligamentum flavum hematoma in the rigid thoracic spine : a case
      report and review of the literature.
AB  - Ligamentum flavum hematoma is a rare condition. Twenty cases including present
      case have been reported in English-language literature. Among them, only one case
      reported in pure thoracic spine. A 72-year-old man presented with thoracic
      myelopathy without precedent cause. Magnetic resonance images revealed a
      posterior semicircular mass which was located in T7 and T8 level compressing the
      spinal cord dorsally. T7-8 total laminectomy and extirpation of the mass was
      performed. One month later following surgery, the patient fully recovered to
      normal state. Pathologic result was confirmed as ligamentum flavum hematoma.
      Ligamentum flavum hematoma of rigid thoracic spine is a very rare disease entity.
      Most reported cases were confined to mobile cervical and lumbar spine. Surgeons
      should be aware that there seems to be another different pathogenesis other than
      previously reported cases of mobile cervical and lumbar spine.

PMID- 19096658
TI  - Short segment anterior correction of adolescent idiopathic scoliosis.
AB  - OBJECTIVE: The purpose of this study was to introduce our surgical experiences of
      scoliosis and to evaluate the effectiveness of anterior correction and fusion in
      adolescent idiopathic scoliosis (AIS). METHODS: Between August 2004 and August
      2007, four patients with AIS were treated with anterior segmental fusion and
      fixation at our hospital. Mean follow-up period was 9 (6-12) months. The average
      age was 14.0 (13-15) years. According to Lenke classification, three patients
      showed Lenke 1 curve and one patient with Lenke 5 curve. Single rod
      instrumentation was performed in one patient, dual rod instrumentation in one
      patient and combined rod instrumentation in two patients. Coronal Cobb
      measurements were performed on all curves in thoracic, thoracolumbar and, lumbar
      spine and the angle of hump was measured by a scoliometer pre- and
      postoperatively. RESULTS: The average operative time was 394 minutes (255-525)
      with an average intraoperative blood loss of 1,225 ml (1,000-1,700). The mean
      period of hospital stay was 19.3 days and there was no complication related to
      the surgery. The mean Cobb angle was reduced from 43.3 degrees to 14.8 degrees
      (65.8% correction) postoperatively and the rib hump corrected less than 5 degrees
      . All patients and their parents were satisfied with the deformity correction.
      CONCLUSION: Anterior spinal correction and fusion of AIS with Lenke 1 and 5 curve
      showed excellent deformity correction without any complications. In particular,
      we recommend anterior dual rod instrumentation because of mechanical stability,
      better control of kyphosis, and a higher fusion rate.

PMID- 19096659
TI  - Vertebral artery dissection: natural history, clinical features and therapeutic
      considerations.
AB  - When a tear occurs in one of the major cervicocerebral arteries and allows blood
      to enter the wall of the artery and split its layers, the result is either
      stenosis or aneurysmal dilatation of the vessel. Vertebral artery dissection
      (VAD) is an infrequent occurrence but is a leading cause of stroke in young and
      otherwise healthy patients. This article discusses recent developments in
      understanding of the epidemiology and pathogenesis of VAD and the various
      clinical manifestations, methods of diagnosis, and approaches to treatment.

PMID- 19096660
TI  - Intracranial Fusiform Aneurysms: It's Pathogenesis, Clinical Characteristics and
      Managements.
AB  - OBJECTIVE: The objective of this study is to investigate clinical
      characteristics, management methods and possible causes of intracranial fusiform
      aneurysm. METHODS: Out of a series of 2,458 intracranial aneurysms treated
      surgically or endovascularly, 22 patients were identified who had discrete
      fusiform aneurysms. Clinical presentations, locations, treatment methods and
      possible causes of these aneurysms were analyzed. RESULTS: Ten patients of
      fusiform aneurysm were presented with hemorrhage, 5 patients with dizziness
      with/without headache, 4 with ischemic neurologic deficit, and 1 with 6th nerve
      palsy from mass effect of aneurysm. Two aneurysms were discovered incidentally.
      Seventeen aneurysms were located in the anterior circulation, other five in the
      posterior circulation. The most frequent site of fusiform aneurysm was a middle
      cerebral artery. The aneurysms were treated with clip, and/or wrapping in 7,
      resection with/without extracranial-intracranial (EC-IC) bypass in 6, proximal
      occlusion with coils with/without EC-IC bypass in 5, EC-IC bypass only in 1 and
      conservative treatment in 3 patient. We obtained good outcome in 20 out of 22
      patients. The possible causes of fusiform aneurysms were regard as dissection in
      16, atherosclerosis in 4 and collagen disease or uncertain in 2 cases.
      CONCLUSION: There is a subset of cerebral aneurysms with discrete fusiform
      morphology. Although the dissection or injury of internal elastic lamina of the
      cerebral vessel is proposed as the underlying cause for most of fusiform
      aneurysm, more study about pathogenesis of these lesions is required.

PMID- 19096661
TI  - Comparative Analysis of Cervical Lateral Mass Screw Insertion among Three
      Techniques in the Korean Population by Quantitative Measurements with Reformatted
      2D CT Scan Images: Clinical Research.
AB  - OBJECTIVE: Our purpose of this study is to compare insertion angles and screw
      lengths from Roy-Camille, Magerl, and our designed method for cervical lateral
      mass screw fixation in the Korean population by quantitative measurement of
      reformatted two dimensional (2D) computed tomography (CT) images. METHODS: We
      selected thirty Korean patients who were evaluated with thin section CT scans and
      reconstruction program to obtain reformatted 2D-CT images of the transversal
      plane passing the cranio-caudal angle using three different techniques. We
      measured the minimum angle to avoid vertebral artery (VA) injury, the ideal angle
      and depth for bicortical screwing of cervical lateral mass. Morphometric
      measurements of the lateral masses from C3-C7 were also taken. RESULTS: In all
      three techniques, the mean safety angles from the VA were less than 8 degrees and
      the necessary depth of the screw was about 14 mm for safety to the VA and for the
      bicortical purchase. In our designed technique, the mean beta angles of each
      level from C3 to C7 were 29.0, 29.8, 29.5, 26.3, and 23.9 degrees, respectively.
      CONCLUSION: Results of this study and data from the literature indicate that
      differences may exist between the Korean and Western people in the length and
      angle for ideal lateral mass screw fixation. In addition, our technique needs
      further cadaveric and clinical study for safety and efficacy for being performed
      as alternative method for cervical lateral mass fixation.

PMID- 19096662
TI  - Microvascular decompression for hemifacial spasm associated with vertebrobasilar
      artery.
AB  - OBJECTIVE: Hemifacial spasm (HFS) is considered as a reversible
      pathophysiological condition mainly induced by continuous vascular compression of
      the facial nerve root exit zone (REZ) at the cerebellopontine angle. As an
      offending vessel, vertebrobasilar artery tends to compress much more heavily than
      others. The authors analyzed HFS caused by vertebrobasilar artery and described
      the relationships between microsurgical findings and clinical courses. METHODS:
      Out of 1,798 cases treated with microvascular decompression (MVD) from Jan. 1980
      to Dec. 2004, the causative vessels were either vertebral artery or basilar
      artery in 87 patients. Seventy-nine patients were enrolled in this study.
      Preoperatively, computed tomography (CT) or brain magnetic resonance (MR) imaging
      with 3-dimentional short range MR technique was performed and CT was checked
      immediately or 2-3 days after anesthetic recovery. The authors retrospectively
      analyzed the clinical features, the compression patterns of the vessels at the
      time of surgery and treatment outcomes. RESULTS: There were 47 were male and 32
      female patients. HFS developed on the left side in 52 cases and on the right side
      in 27. The mean age of onset was 52.3 years (range 19-60) and the mean duration
      of symptoms was 10.7 years. Many patients (39 cases; 49.1%) had past history of
      hypertension. HFS caused only by the vertebral artery was 8 cases although most
      of the other cases were caused by vertebral artery (VA) in combination with its
      branching arteries. Most frequently, the VA and the posterior inferior cerebellar
      artery (PICA) were the simultaneous causative blood vessels comprising 32 cases
      (40.5%), and in 27 cases (34.2%) the VA and the anterior inferior cerebellar
      artery (AICA) were the offenders. Facial symptoms disappeared in 61 cases (77.2%)
      immediately after the operation and 68 cases (86.1%) showed good outcome after 6
      months. Surgical outcome just after the operation was poor in whom the
      perforators arose from the offending vessels concurrently (p<0.05). CONCLUSION:
      In case where the vertebral artery is a cause of HFS, commonly branching arteries
      associated with main arterial compression on facial REZ requires more definite
      treatment for proper decompression because of its relatively poor results
      compared to the condition caused by other vascular compressive origins.

PMID- 19096663
TI  - Familial intracranial aneurysms.
AB  - OBJECTIVE: Numerous studies have compared the characteristics of familial
      intracranial aneurysms with those of non-familial aneurysms. To better understand
      familial subarachnoid hemorrhage (SAH), we studied a series of patients with SAH
      who had at least one first-degree relative with SAH, and compared our results
      with those of previous studies. METHODS: We identified patients treated for SAH
      at our hospital between January 1993 and October 2006 and analyzed those patients
      with one or more first-degree relatives with SAH. We retrospectively collected
      data from patients with a family history and searched for patients who had
      relatives with aneurysms or who had been treated at other hospitals for SAH.
      RESULTS: We identified 12 patients from six families with at least two first
      degree relatives with SAH. All patients had affected first-degree relatives; in
      five families, they were siblings. The mean age at the time of rupture was 49.75
      years; in four families, the age difference was within 5 years. In five patients
      (42%), the aneurysm was located in the middle cerebral artery. Only one patient
      had an aneurysm in the anterior communicating artery. CONCLUSION: In agreement
      with previous studies, our results showed that familial aneurysms, in comparison
      with non-familiar aneurysms, ruptured at a younger age and smaller size, had a
      high incidence in the middle cerebral artery, and were underrepresented in the
      anterior communicating artery. Interestingly, the age at the time of rupture was
      similar between relatives. Screening should be considered in the fifth or sixth
      decade for those who have a sibling with SAH.

PMID- 19096664
TI  - The effect of barbiturate coma therapy for the patients with severe intracranial
      hypertension: a 10-year experience.
AB  - OBJECTIVE: Barbiturate coma therapy (BCT) has been known to be an useful method
      to control increased intracranial pressure (IICP) refractory to medical and
      surgical treatments. We have used BCT for patients with severe IICP during the
      past 10 years, and analyzed our results with review of literatures. METHODS: We
      analyzed 92 semicomatose or comatose patients with Glasgow coma scale (GCS) of 7
      or less with severe IICP due to cerebral edema secondary to parenchymal damages
      irrespective of their causes. Forty patients who had received BCT with ICP
      monitoring from January 1997 to December 2006 were included in BCT group, and
      fifty-two patients who had been managed without BCT from January 1991 to December
      1995 were divided into control group. We compared outcomes with Glasgow outcome
      scale (GOS) and survival rate between the two groups. RESULTS: Good outcome
      (GOS=4 and 5) rates at 3-month after insult were 27.5% and 5.8% in BCT and
      control group, respectively (p<0.01). One-year survival rates were 35.9% and
      12.5% in BCT and control group, respectively (p<0.01). In BCT group, the mean age
      of good outcome patients (37.1 +/- 14.9) was significantly lower than that of
      poor outcome patients (48.1 +/- 13.5) (p<0.05). CONCLUSION: With our 10-year
      experience, we suggest that BCT is an effective treatment method for severe IICP
      patients for better survival and GOS, especially for younger patients.

PMID- 19096665
TI  - Surgical treatment of orbital tumors at a single institution.
AB  - OBJECTIVE: The authors reviewed the experience of 19 patients with orbital tumors
      and summarize the clinical features, surgical treatment and outcomes. METHODS:
      The authors searched the database for all patients who underwent surgery for the
      treatment of orbital tumors at a single institution between 1999 and 2007. Data
      from clinical notes, surgical reports, and radiological findings were obtained
      for the analysis. RESULTS: Orbital tumors constituted a heterogenous array of
      histopathology. The presenting symptoms were exophthalmos (52.6%), visual
      disturbance (26.3%) and pain (21.1%). The surgical approaches used were
      transcranial in 17 patients. Tumors located in the intraconal or perioptic space
      were surgically excised using a frontoorbital approach (8 cases), while pterional
      (3 cases), orbital (2 cases) and combined approaches (6 cases) were used for
      tumors in other sites. Total resection of tumors was achieved in 12 of 19
      patients. In 4 patients with glioma and lymphoma only diagnostic biopsy was done.
      Three patients experienced visual deterioration postoperatively. Two patients had
      temporary diplopia, and one patient had temporary ptosis. CONCLUSION: Surgical
      treatment could be the mainstay of therapy for the majority of symptomatic
      orbital tumors. Many orbital tumors can be treated safely via a transcranial
      approach. Frontoorbital approach allows the surgeon to reach both the
      intraorbital and intracranial structures. Knowledge of the microanatomy of the
      orbit and meticulous surgical skills are necessary to overcome the pitfalls of
      intraorbital surgery.

PMID- 19096666
TI  - Endocrine outcome of endoscopic endonasal transsphenoidal surgery in functioning
      pituitary adenomas.
AB  - OBJECTIVE: Microscopic and endoscopic transsphenoidal approach (TSA) are major
      surgical techniques in the treatment of pituitary adenoma. Endoscopic endonasal
      transsphenoidal approach (EETSA) has been increasingly used for pituitary
      adenomas, however, its surgical outcome particularly in functioning pituitary
      adenoma has been debated. Here, we investigated the endocrine outcome of the
      patients with growth hormone (GH) and adrenocorticotropic hormone (ACTH)
      secreting pituitary adenoma treated by EETSA. METHODS: We treated 80 patients
      with pituitary adenoma by EETSA since 2004, of which 12 patients were affected by
      functioning pituitary adenomas (9 GH, 3 ACTH, 0 PRL; 9 macro, 3 micro). Surgical
      outcome of those patients treated by EETSA was compared with that of the 11
      functioning pituitary adenoma patients (8 GH, 3 ACTH; 8 macro, 3 micro) who
      underwent sublabial microscopic TSA between 1997 and 2003. RESULTS: Imaging
      remission based on postoperative MRI was achieved in 8 (73%) and hormonal
      remission in 5 (45%) of 11 patients treated by sublabial microscopic TSA. Imaging
      remission was observed in 10 (83%, p=0.640) and hormonal remission in 10 (83%,
      p=0.081) of 12 patients by EETSA. CSF leakage was noticed in 2 (17%) of EETSA
      group and in 2 (18%) of sublabial microscopic TSA group. Panhypopituitarism was
      observed in 1 (9%) of EETSA group and in 3 (27%) of sublabial microscopic TSA
      group. CONCLUSION: EETSA appears to be an effective and safe method for the
      treatment of functioning pituitary adenomas.

PMID- 19096667
TI  - Spontaneous intraorbital hemorrhage: a case report.
AB  - Intraorbital hemorrhage is a rare clinical condition caused by orbital trauma,
      surgery around the orbit, intraorbital vascular abnormalities, and neoplasm. It
      was reported to occur spontaneously without any known causes and in association
      with orbital pseudotumor in a very few cases. A 59-year-old, female patient
      admitted with sudden onset of severe exophthalmos and pain on the left eye.
      Orbital CT and MR imaging suggested hemorrhage in the upper part of retrobulbar
      area of the left orbit. Cerebral angiography was taken to rule out any possible
      vascular abnormalities. On the left carotid cerebral angiography, the run-off of
      the distal ophthalmic artery was not seen and the engorgement of the
      supraophthalmic artery was noted. Systemic administration of corticosteroid did
      not improve the clinical status and craniectomy was done and retrobulbar hematoma
      was removed, and the clinical symptoms and signs were improved. Authors report a
      case of spontaneous intraorbital hemorrhage with the clinical features similar to
      those of orbital pseudotumor, requiring surgical decompression.

PMID- 19096668
TI  - Contralateral cerebral infarction after stent placement in carotid artery: an
      unexpected complication.
AB  - Stenting is a useful alternative treatment modality in carotid artery stenosis
      patients who are too high-risk to undergo carotid endarterectomy (CEA). We report
      a case of contralateral cerebral infarction after stenting for extracranial
      carotid stenosis. A 78-year-old woman was admitted to the hospital with left
      sided weakness. Based on magnetic resonance imaging (MRI) of the brain and
      conventional angiography, she was diagnosed with an acute watershed infarct of
      the right hemisphere secondary to severe carotid stenosis. Stenting was performed
      for treatment of the right carotid artery stenosis after a one-week cerebral
      angiogram was completed. Thirty minutes after stent placement, the patient
      exhibited a generalized seizure. Four hours later, brain MRI revealed left
      hemispheric cerebral infarction. Complex aorta-like arch elongation, tortuosity,
      calcification, and acute angulation at the origin of the supra-aortic arteries
      may increase the risk of procedural complications. In our case, we suggest that
      difficult carotid artery catheterization, with aggressive maneuvering during
      stenting, likely injured the tortuous, atherosclerotic aortic arch, and led to
      infarction of the contralateral cerebral hemisphere by thromboemboli formed on
      the wall of the atherosclerotic aorta.

PMID- 19096669
TI  - Endovascular treatment of "kissing aneurysms" at the anterior communicating
      artery.
AB  - Kissing aneurysms are the rare type of multiple aneurysms. They are adjacent
      aneurysms of different origin arteries in the same region, which require great
      care in diagnosis and treatment. We report a case of kissing aneurysms at the
      anterior communicating artery (AcomA) which were treated by endovascular coil
      embolization.

PMID- 19096670
TI  - Sacral insufficiency fracture, usually overlooked cause of lumbosacral pain.
AB  - Sacral insufficiency fractures are usually known to develop in elderly patients
      with osteoporosis without definite trauma history. It is difficult to diagnose
      the sacral insufficiency fracture at an early stage because lower lumbar
      diseases, concurrently or not, may also be presented with similar symptoms and
      signs. We report a rare case of sacral insufficiency fracture who was not
      diagnosed initially but, instead, showed progressively worsening of clinical
      symptoms and radiological findings after decompression surgery for upper level
      lumbar stenosis.

PMID- 19096671
TI  - Upward migration of distal ventriculoperitoneal shunt catheter into the heart:
      case report.
AB  - Ventriculoperitoneal (VP) shunt is commonly and effectively used to treat
      hydrocephalus. Intracardiac migration of the shunt catheter is a rare
      complication. A 68-year-old woman underwent ventriculoperitoneal shunting for
      hydrocephalus secondary to subarachnoid hemorrhage due to anterior communicating
      artery aneurysm rupture. Two weeks after the shunt surgery, she had suffered from
      the abdominal pain. Plain chest x-rays, computed tomography, and echocardiography
      revealed the distal catheter which was in the right ventricle of the heart. We
      tried to remove the catheter through the internal jugular vein by fluoroscopic
      guidance. But, the distal catheter was kinked and knotted; therefore, we failed
      to withdraw the catheter. After then, we punctured the right femoral vein and
      pulled down the multi-knotted shunt catheter to the femoral vein using the snare
      catheter. Finally, we removed the knotted distal catheter via the femoral vein
      and a new distal catheter was placed into the peritoneal cavity. We report a case
      in which the distal catheter of the VP shunt migrated into the heart via the
      internal jugular vein. We emphasize the importance of careful and proper
      placement of the distal catheter during the tunneling procedure to prevent life
      threatening complications.

PMID- 19096672
TI  - Two cases of symptomatic perineural cysts (tarlov cysts) in one family: a case
      report.
AB  - Symptomatic sacral perineural cysts are uncommon. Several hypotheses have been
      proposed to explain the etiologies of perineural cysts, but the accurate
      etiologies remain unclear. We experienced two cases of symptomatic sacral
      perineural cysts (Tarlov cysts) in one family, who presented with perianal
      paresthesia. Both of them were operated and postoperatively their symptoms were
      disappeared immediately. We experienced the excellent treatment outcome with the
      surgical management of symptomatic perineural cysts in the sacral region. We
      assume that the theory of congenital origin including a familial tendency is the
      most plausible of the hypotheses that have been proposed.

PMID- 19096673
TI  - Extravasation during Aneurysm Embolization without Neurologic Consequences.
      Lessons learned from Complications of Pseudoaneurysm Coiling. Report of 2 Cases.
AB  - Although endovascular intervention is the first-line treatment of intracranial
      aneurysm, intraprocedural rupture or extravasation is still an endangering event.
      We describe two interesting cases of extravasation during embolotherapy for
      ruptured peripheral cerebral pseudoaneurysms. Two male patients were admitted
      after development of sudden headache with presentation of intracerebral and
      subarachnoid hemorrhage, respectively. Initial angiographic assessment failed to
      uncover any aneurysmal dilatation in both patients. Two weeks afterwards,
      catheter angiography revealed aneurysms each in the peripheral middle cerebral
      artery and anterior inferior cerebellar artery. Under a general anesthesia,
      endovascular embolization was attempted without systemic heparinization. In each
      case, sudden extravasation was noted around the aneurysm during manual injection
      of contrast after microcatheter navigation. Immediate computed tomographic scan
      showed a large amount of contrast collection within the brain, but they tolerated
      and made an unremarkable recovery thereafter. Intraprocedural extravasation is an
      endangering event and needs prompt management, however proximal plugging with
      coil deployment can be sufficient alternative, if one confronts with peripheral
      pseudoaneurysm. Peculiar angiographic features are deemed attributable to
      extremely fragile, porous vascular wall of the pseudoaneurysm. Accordingly, it
      should be noted that extreme caution being needed to handle such a friable
      vascular lesion.

PMID- 19096674
TI  - Stereotactic multiplanar reformatted computed tomography-guided catheter
      placement and thrombolysis of spontaneous intracerebral hematomas.
AB  - OBJECTIVE: The authors present their experiences with stereotactic multiplanar
      reformatted (MPR) computed tomography (CT)-guided catheter placement for
      thrombolysis of spontaneous intracerebral hematoma (sICH) and their clinical
      results. METHODS: In 23 patients with sICH, MPR CT-guided catheter placement was
      used to select the trajectory and target point of hematoma drainage. This group
      was comprised of 11 men and 12 women, and the mean age was 57.5 years (range, 31
      79 years). The patients' initial Glasgow Coma Scale scores ranged from 7 to 15
      with a median of 11. The volume of the hematoma ranged from 24 mL to 86 mL (mean
      44.5 mL). A trajectory along the main axis of the hematoma was considered to be
      optimal for thrombolytic therapy. The trajectory was calculated from the point of
      entry through the target point of the hematoma using reformatted images. RESULTS:
      The hematoma catheter was left in place for a median duration of 48.9 hours
      (range 34 to 62 hours). In an average of two days, the average residual hematoma
      volume was 6.2 mL (range 1.4 mL to 10.2 mL) and was reduced by an average of
      84.7% (range 71.6% to 96.3%). The residual hematoma at postoperative seven days
      was less than 5 mL in all patients. There was no treatment-related death during
      hospitalization. CONCLUSION: The present study indicates that stereotactic MPR CT
      guided catheter placement for thrombolysis is an accurate and safe procedure. We
      suggest that this procedure for stereotactic removal of sICH should be considered
      for the optimization of the trajectory selection in the future.

PMID- 19096675
TI  - Clinical and angiographic results after treatment with combined clipping and
      wrapping technique for intracranial aneurysm.
AB  - OBJECTIVE: There have been numerous follow-up studies of patients who had
      ruptured or unruptured intracranial aneurysms treated by wrapping technique using
      various materials have been reported. Our objective was to ascertain whether our
      particular wrapping technique using the temporalis muscle provides protection
      from rebleeding and any aneurysm configuration changes in follow-up studies.
      METHODS: Clinical presentation, the location and shape of the aneurysm, outcomes
      at discharge and last follow-up, and any aneurysm configuration changes on last
      angiographic study were analyzed retrospectively in 21 patients. Reinforcement
      was acquired by clipping the wrapped temporalis muscle. Wrapping and clipping
      after incomplete clipping was also done. Follow-up loss and non-angiographic
      follow-up patient groups were excluded in this study. RESULTS: The mean age was
      53 years (range 29-67), and 15 patients were female. Among 21 patients, 10
      patients had ruptured aneurysms (48%). Aneurysms in 21 patients were located in
      the anterior circulation. Aneurysm shapes were broad neck form (14 cases),
      fusiform (1 case), and bleb to adjacent vessel (6 cases). Five patients were
      treated by clipping the wrapped temporalis, and 16 patients by wrapping after
      partial clipping. The mean Glasgow coma scale (GCS) at admission was 14.2. The
      mean Glasgow outcome scale (GOS) at discharge was 4.8, and 18 patients were grade
      5. The mean period between initial angiography and last angiography was 18.5
      months (range 8-44). Aneurysm size was not increased in any of these patients and
      configuration also did not change. There was no evidence of rebleeding in any of
      these treated aneurysms. CONCLUSION: Our study results show that wrapping
      technique, using the temporalis muscle and aneurysm clip(s), for intracranial
      aneurysm treatment provides protection from rebleeding or regrowth.

PMID- 19096676
TI  - Effect of vagus nerve stimulation in post-traumatic epilepsy and failed epilepsy
      surgery : preliminary report.
AB  - OBJECTIVE: Vagus nerve stimulation (VNS) has been used in epilepsy patients
      refractory to standard medical treatments and unsuitable candidates for resective
      or disconnective surgery. In this study, we investigated the efficacy of VNS to
      patients who had refractory result to epilepsy surgery and patients with post
      traumatic epilepsy. METHODS: We analyzed the effect of VNS in 11 patients who had
      undergone previous epilepsy surgery and patients with intractable post-traumatic
      epilepsy associated with brain injury. All patients underwent VNS implantation
      between October 2005 and December 2006. RESULTS: We evaluated seizure frequency
      before and after implantation of VNS and maximum follow up period was 24 months.
      In the first 6 months, 11 patients showed an average of 74.3% seizure reduction.
      After 12 months, 10 patients showed 85.2% seizure reduction. Eighteen months
      after implantation, 9 patients showed 92.4% seizure reduction and 7 patients
      showed 97.2% seizure reduction after 24 months. Six patients were seizure-free at
      this time. CONCLUSION: We conclude that the VNS is a helpful treatment modality
      in patients with surgically refractory epilepsy and in patients with post
      traumatic epilepsy due to severe brain injury.

PMID- 19096677
TI  - The Treatment Outcome of Elderly Patients with Idiopathic Trigeminal Neuralgia :
      Micro-Vascular Decompression versus Gamma Knife Radiosurgery.
AB  - OBJECTIVE: This study was designed to compare the efficacy of micro-vascular
      decompression (MVD) and Gamma knife radiosurgery (GKRS) for elderly idiopathic
      trigeminal neuralgia patients by analyzing the clinical outcome. METHODS: In the
      past 10 years, 27 elderly patients were treated with MVD while 18 patients were
      treated with GKRS (>65-years-old). We reviewed their clinical characteristics and
      clinical courses after treatment as well as the treatment outcomes. For patients
      who were treated with MVD, additional treatment methods such as rhizotomy were
      combined in some areas. In GKRS, we radiated the root entry zone (REZ) with the
      mean maximum dose of 77.8 (70-84.3) Gy and one 4 mm collimator. RESULTS: The mean
      age was 68.1 years for MVD, and 71.1 years for GKS group. The average time
      interval between first presenting symptom and surgery was 84.1 (1-361) months,
      and 51.4 (1-120) months, respectively. The mean follow-up period after the
      surgery was 35.9 months for MVD, and 33.1 months for GKRS. According to Pain
      Intensity Scale, MVD group showed better prognosis with 17 (63%) cases in grade I
      II versus 10 (55.6%) cases in GKRS group after the treatment. The pain recurrence
      rate during follow up did not show much difference with 3 (11.1%) in MVD, and 2
      (11.1%) in GKRS. After the treatment, 2 cases of facial numbness, and 1 case each
      of herpes zoster, cerebrospinal fluid (CSF) leakage, hearing disturbance, and
      subdural hematoma occurred in MVD Group. In GKRS, there was 1 (5.6%) case of
      dysesthesia but was not permanent. Three cases were retreated by GKRS but the
      prognosis was not as good as when the surgery was used as primary treatment, with
      1 case of grade I-II, and 1 case of recurrence. The maximal relieve of pain was
      seen just after surgery in MVD group, and 1 year after treatment in GKRS group.
      CONCLUSION: For trigeminal neuralgia patients with advanced age, MVD showed
      advantages in immediately relieving the pain. However, in overall, GKRS was
      preferable, despite the delayed pain relief, due to the lower rate of surgical
      complications that arise owing to the old age.

PMID- 19096678
TI  - Aneurysms of distal posterior inferior cerebellar artery.
AB  - OBJECTIVE: Aneurysms are very rarely encountered in the distal posterior inferior
      cerebellar artery (PICA). The authors experienced 5 cases with a distal PICA
      aneurysm among 368 cases of intracranial aneurysms during the period from January
      2003 to January 2008. Here, the authors describe their clinical and surgical
      experiences and include a review of the relevant literature. METHODS: Using
      radiologic findings and charts, we retrospectively reviewed the surgical results
      of 5 cases with a distal PICA aneurysm treated from January 2003 to January 2008.
      RESULTS: The current five cases were composed of four cases of 'Good' and one
      case of 'Fair'. No postoperative complications occurred other than a ventriculo
      peritoneal shunt due to hydrocephalus in Case 2. In all five cases, treatment was
      successful without neurological deficit. CONCLUSION: Surgical outcome of PICA
      aneurysms have been reported to be excellent because the amount of
      intraparenchymal injury is limited. More clinical experience, microsurgical
      technique developments, and endovascular surgery advancements are certain to
      improve treatment outcomes.

PMID- 19096679
TI  - Comparative Study of Outcomes between Shunting after Cranioplasty and in
      Cranioplasty after Shunting in Large Concave Flaccid Cranial Defect with
      Hydrocephalus.
AB  - OBJECTIVE: The cranioplasty and ventriculoperitoneal (VP) shunt operation have
      been used to treat a large cranial defect with posttraumatic hydrocephalus (PTH).
      The aim of this study was to evlauate the difference of outcomes between in the
      shunting after the cranioplasty (group 1) and the cranioplasty after the shunting
      (group 2) in a large flaccid cranial defect with PTH. METHODS: In this study, a
      retrospective review was done on 23 patients undergoing the cranioplasty and VP
      shunt operation after the decompressive craniectomy for a refractory intracranial
      hypertension from 2002 to 2005. All of 23 cases had a large flaccid concave
      cranial defect and PTH. Ten cases belong to group 1 and 13 cases to group 2. The
      outcomes after operations were compared in two groups 6 months later. RESULTS:
      The improvement of Glasgow outcome scale (GOS) was seen in 8 cases (80.0%) of
      total 10 cases in group 1, and 6 cases (46.2%) of 13 cases in group 2. Three
      (75.0%) of 4 cases with hemiparesis in group 1 and 3 of 6 cases (50.0%) in group
      2 were improved. All cases (2 cases) with decrease of visual acuity were improved
      in each group. Dysphasia was improved in 3 of 5 cases (60%) in group 1 and 4 of 6
      cases (66.6%) in group 2. CONCLUSION: These results suggest that outcomes in
      group 1 may be better than in group 2 for a large flaccid concave cranial defect
      with PTH.

PMID- 19096680
TI  - Comparative analysis of cervical arthroplasty using mobi-c(r) and anterior
      cervical discectomy and fusion using the solis(r) -cage.
AB  - OBJECTIVE: Although anterior cervical discectomy and fusion (ACDF) is the
      standard treatment for degenerative cervical disc disease, concerns regarding
      adjacent level degeneration and loss of motion have suggested that arthroplasty
      may be a better alternative. We have compared clinical and radiological results
      in patients with cervical disc herniations treated with arthroplasty and ACDF.
      METHODS: We evaluated 53 patients treated for cervical disc herniations with
      radiculopathy, 21 of whom underwent arthroplasty and 32 of whom underwent ACDF.
      Clinical results included the Visual Analogue Scale (VAS) score for upper
      extremity radiculopathy, neck disability index (NDI), duration of hospital stay
      and convalescence time. All patients were assessed radiologically by measuring
      cervical lordosis, segmental lordosis and segmental range-of-movement (ROM) of
      operated and adjacent disc levels. RESULTS: Mean hospital stay (5.62 vs. 6.26
      days, p<0.05) and interval between surgery and return to work (1.10 vs. 2.92
      weeks, p<0.05) were significantly shorter in the arthroplasty than in the fusion
      group. Mean NDI and extremity VAS score improved after 12 months in both groups.
      Although it was not significant, segmental ROM of adjacent levels was higher in
      the fusion group than in the arthroplasty group. And, segmental motion of
      operated levels in arthroplasty group maintained more than preoperative value at
      last follow up. CONCLUSION: Although clinical results were similar in the two
      groups, postoperative recovery was significantly shorter in the arthroplasty
      group. Although it was not significant, ROM of adjacent segments was less in the
      arthroplasty group. Motion of operated levels in arthroplasty group was preserved
      at last follow up.

PMID- 19096681
TI  - The outcomes of concomitant chemoradiotherapy followed by adjuvant chemotherapy
      with temozolomide for newly diagnosed high grade gliomas : the preliminary
      results of single center prospective study.
AB  - OBJECTIVE: Malignant gliomas are the most common primary cerebral neoplasms in
      adults. Despite multimodality treatments, the prognosis for patients with
      malignant glioma remains poor. However, recently, the effectiveness of
      concomitant chemoradiotherapy (CCRT) with temozolomide (TMZ) has been reported.
      We report for the first time preliminary results of the treatment with CCRT of
      newly diagnosed malignant gliomas in Korean people. METHODS: Thirty-two patients
      over the age of 17 years with newly diagnosed and histologically confirmed high
      grade gliomas (HGG), from June 2004 to August 2007 were the subjects of this
      study. There were 17 men and 15 women, with a median age of 53.5 years (range, 17
      74). Pathologically, glioblastoma, anaplastic astrocytoma, anaplastic
      oligodendroglioma, and gliomatosis cerebri had been diagnosed in eighteen, eight,
      four, and two patients, respectively. These 32 patients were treated with CCRT
      with TMZ. RESULTS: The median follow-up period was 12.5 months (range 3-48). At
      the time of this analysis, 13 patients died and three patients had been lost to
      follow-up. There was no mortality caused by drug toxicity. The median progression
      free survival (PFS) of these patients was 9.0 months, and the six-month PFS rate
      was 72.4%. The median overall survival (OS) was 26 months, and the one-year OS
      rate was 83.6%. The 18 patients with glioblastoma were analyzed separately from
      the other patients with HGG, and the median OS was 18 months, and the one-year OS
      rates were 81.8%. The median PFS was seven months, and the six-month PFS rate was
      75.0%. CONCLUSION: Our results are consistent with many other reports, confirming
      that CCRT with TMZ achieves good clinical outcomes in the treatment of HGG.
      Therefore, we suggest that CCRT with TMZ as adjuvant chemotherapy be considered
      as a standard therapy for patients with HGG.

PMID- 19096682
TI  - Result of extracranial-intracranial bypass surgery in the treatment of complex
      intracranial aneurysms : outcomes in 15 cases.
AB  - OBJECTIVE: The standard treatment strategy of intracranial aneurysms includes
      either endovascular coiling or microsurgical clipping. In certain situations such
      as in giant or dissecting aneurysms, bypass surgery followed by proximal
      occlusion or trapping of parent artery is required. METHODS: The authors assessed
      the result of extracranial-intracranial (EC-IC) bypass surgery in the treatment
      of complex intracranial aneurysms in one institute between 2003 and 2007
      retrospectively to propose its role as treatment modality. The outcomes of 15
      patients with complex aneurysms treated during the last 5 years were reviewed.
      Six male and 9 female patients, aged 14 to 76 years, presented with symptoms
      related to hemorrhage in 6 cases, transient ischemic attack (TIA) in 2 unruptured
      cases, and permanent infarction in one, and compressive symptoms in 3 cases.
      Aneurysms were mainly in the internal carotid artery (ICA) in 11 cases, middle
      cerebral artery (MCA) in 2, posterior cerebral artery (PCA) in one and posterior
      inferior cerebellar artery (PICA) in one case. RESULTS: The types of aneurysms
      were 8 cases of large to giant size aneurysms, 5 cases of ICA blood blister-like
      aneurysms, one dissecting aneurysm, and one pseudoaneurysm related to trauma.
      High-flow bypass surgery was done in 6 cases with radial artery graft (RAG) in
      five and saphenous vein graft (SVG) in one. Low-flow bypass was done in nine
      cases using superficial temporal artery (STA) in eight and occipital artery (OA)
      in one case. Parent artery occlusion was performed with clipping in 9 patients,
      with coiling in 4, and with balloon plus coil in 1. Direct aneurysm clip was done
      in one case. The follow up period ranged from 2 to 48 months (mean 15.0 months).
      There was no mortality case. The long-term clinical outcome measured by Glasgow
      outcome scale (GOS) showed good or excellent outcome in 13/15. The overall
      surgery related morbidity was 20% (3/15) including 2 emergency bypass surgeries
      due to unexpected parent artery occlusion during direct clipping procedure. The
      short-term postoperative bypass graft patency rates were 100% but the long-term
      bypass patency rates were 86.7% (13/15). Nonetheless, there was no bypass surgery
      related morbidity due to occlusion of the graft. CONCLUSION: Revascularization
      technique is a pivotal armament in managing complex aneurysms and scrupulous
      prior planning is essential to successful outcomes.

PMID- 19096683
TI  - Surgical complications of epilepsy surgery procedures : experience of 179
      procedures in a single institute.
AB  - OBJECTIVE: There are a few reports on the complications of surgery for epilepsy.
      We surveyed our data to present complications of epilepsy surgeries from the
      neurosurgeon's point of view and compare our results with other previous reports.
      METHODS: A total of 179 surgical procedures for intractable epilepsy (41
      diagnostic, 138 therapeutic) were performed in 92 consecutive patients (10
      adults, 82 children) during the last 9.2 years (February. 1997-April. 2006).
      Their medical records and radiological findings were reviewed to identify and
      analyze the surgical complications. RESULTS: The diagnostic procedures
      encompassed various combinations of subdural grid, subdural strips, and depth
      electrodes. Four minor transient complications developed in 41 diagnostic
      procedures (4/41=9.8%). A total of 138 therapeutic procedures included 28
      anterior temporal lobectomies, 21 other lobectomies, 6 lesionectomies, 21
      topectomies, 13 callosotomies, 20 vagus nerve stimulations, 13 multiple subpial
      transections, and 16 hemispherectomies. Twenty-six complications developed in
      therapeutic procedures (26/138=18.8%). Out of the 26 complications, 21
      complications were transient and reversible (minor; 21/138=15.2%), and 5 were
      serious complications (major; 5/138=3.6%). Five major complications were one
      visual field defect, two mortality cases and two vegetative states. There were 2
      additional mortality cases which were not related to the surgery itself.
      CONCLUSION: Our results indicate that complication rate was higher than previous
      other reports in minor complications and was comparable in major complications.
      However, our results show relatively high frequency of mortality cases and severe
      morbidity case compared to other previous reports. The authors would like to
      emphasize the importance of acute postoperative care in young pediatric patients
      as well as meticulous surgical techniques to reduce morbidity and mortality in
      epilepsy surgery.

PMID- 19096684
TI  - The first neurosurgical analysis of 8 korean children with sotos syndrome.
AB  - OBJECTIVE: Sotos Syndrome is characterized by macrocephaly, overgrowth, and
      developmental delay, and more than 300 patients have been reported worldwide to
      date. The authors reviewed the clinical characteristics of 8 patients with Sotos
      Syndrome in Korea for a new understanding and treatment strategies. METHODS: The
      medical records of a total of eight Korean children with Sotos Syndrome were
      reviewed. All patients underwent developmental checkup, lumbar punctures for
      measurement of intracranial pressure (ICP), brain and spine magnetic resonance
      imaging and computerized tomography. RESULTS: All 8 patients showed macrocephaly
      and the characteristic craniofacial features of Sotos Syndrome. Other clinical
      characteristics shown were overgrowth (7/8), developmental delay (7/8),
      congenital heart defect (3/8), flat foot (8/8), scoliosis (4/8), spina bifida
      (8/8), hydrocephalus (4/8), cavum vergae (3/8), and increased subdural fluid
      collection (5/8). Mean ICP measured via lumbar puncture was 27.35+/-6.25 cm H(2)O
      (range 20 to 36 cm H(2)O). Two patients received ventriculo-peritoneal shunt, and
      1 patient underwent subduro-peritoneal shunt with improvement. Spinal orthosis
      was applied to 4/5 patients with scoliosis and 4/8 children with flat foot were
      provided with foot orthosis. CONCLUSION: In this first Korean study of 8 Sotos
      Syndrome patients we demonstrated the presence of spina bifida and increased ICP,
      which had not been previously described. The authors therefore suggest that all
      patients with Sotos Syndrome should undergo examination for the presence of spina
      bifida, and that shunt procedures would improve development and alleviate
      clinical symptoms.

PMID- 19096685
TI  - Time course of symptom disappearance after microvascular decompression for
      hemifacial spasm.
AB  - OBJECTIVE: This study is to investigate time course of symptom disappearance in
      patients whose spasm relieved completely after microvascular decompression (MVD).
      METHODS: Of 115 patients with hemifacial spasm (HFS) who underwent MVD from April
      2003 to December 2006, 89 patients who had no facial paralysis after operation
      and showed no spasm at last follow-up more than 1.5 years after operation were
      selected. Symptom disappearance with time after MVD was classified into type 1
      (symptom disappearance right after operation), type 2 (delayed symptom
      disappearance) and type 3 (unusual symptom disappearance). Type 2 was classified
      into type 2a (with postoperative silent period) and type 2b (without silent
      period). RESULTS: Type 1, type 2a, type 2b and type 3 were 38.2%, 48.37%, 12.4%
      and 1.1%, respectively. Delayed disappearance group (type 2) was 60.7%. Post
      operative symptom duration in all cases ranged from 0 to 900 days, average was
      74.6 days and median was 14 days. In case of type 2, average post-operative
      symptom duration was 115.1 days and median was 42 days. Five and 3 patients
      required more than 1 year and 2 years, respectively, until complete disappearance
      of spasm. In type 2a, postoperative silent period ranged from 1 to 10 days, with
      an average of 2.4 days. CONCLUSION: Surgeons should be aware that delayed symptom
      disappearance after MVD for HFS is more common than it has been reported, silent
      period can be as long as 10 days and time course of symptom disappearance is
      various as well as unpredictable.

PMID- 19096686
TI  - The neovascularization effect of bone marrow stromal cells in temporal muscle
      after encephalomyosynangiosis in chronic cerebral ischemic rats.
AB  - OBJECTIVE: In Moyamoya disease, the primary goal of treatment is to improve
      collateral circulation through angiogenesis. In the present study, we obtained
      and sub-cultured bone marrow stromal cells (BMSCs) from rats without a cell
      mediated immune response. Then, we injected the labeled BMSCs directly into
      adjacent temporal muscle during encephalomyosynangiosis (EMS). Three weeks after
      BMSC transplantation, we examined the survival of the cells and the extent of
      neovascularization. METHODS: We divided 20 rats into a BMSC transplantation group
      (n=12) and a control group (n=8). Seven days after the induction of chronic
      cerebral ischemia, an EMS operation was performed, and labeled BMSCs
      (1x106(6)/100 microL) were injected in the temporal muscle for the
      transplantation group, while an equivalent amount of culture solution was
      injected for the control group. Three weeks after the transplantation, temporal
      muscle and brain tissue were collected for histological examination and western
      blot analysis. RESULTS: The capillary/muscle ratio in the temporal muscle was
      increased in the BMSC transplantation group compared to the control group,
      showing a greater increase of angiogenesis (p<0.05). In the brain tissue,
      angiogenesis was not significantly different between the two groups. The injected
      BMSCs in the temporal muscle were vascular endothelial growth factor (VEGF)
      positive by immunofluorescence staining. In both temporal muscle and brain
      tissue, the expression of VEGF by western blot analysis was not much different
      between the two groups. CONCLUSION: During EMS in a chronic cerebral ischemia rat
      model, the injection of BMSCs resulted in accelerated angiogenesis in the
      temporal muscle compared to the control group.

PMID- 19096687
TI  - Large Ossified Rathke's Cleft Cyst - A Case Report and Review of the Literature 
      .
AB  - We report a rare case of symptomatic Rathke's cleft cyst with thick calcified
      wall. Brain CT scans revealed a large cystic mass with round thick calcified
      wall. In this case, we selected the pterional approach instead of transsphenoidal
      approach due to the possibility of cystic craniopharyngioma. Histopathologically,
      it was calcified Rathke's cleft cyst with focal epithelial metaplasia. This case
      illustrates that calcification of the suprasellar cyst does not always suggest
      craniopharyngioma and the calcification pattern of Rathke's cleft cyst is
      different from that of the craniopharyngioma.

PMID- 19096688
TI  - Oral extrusion of screw after anterior cervical interbody fusion.
AB  - We present a case of delayed oral extrusion of a screw after anterior cervical
      interbody fusion in a 68-year-old man with osteoporosis. Fifteen months earlier,
      he had undergone C5 corpectomy and anterior cervical interbody fusion at C4-6 for
      multiple spinal stenoses. The patient was nearly asymptomatic, except for a
      foreign body sensation in his throat. We conclude that the use of a mesh graft or
      other instrument in elderly patients and those with osteoporosis or problematic
      bone quality should be considered carefully and that if surgery were to be
      performed, periodic postoperative follow-up evaluations are mandatory.

PMID- 19096689
TI  - Discal cyst of the lumbar spine.
AB  - Discal cysts are rare lesions that can cause radiating leg pain. Because they are
      very rare, their natural history and the details of the therapeutic guidelines
      for the treatment of these cysts are still unknown. A 30-year-old male patient
      presented to our institute with radiating pain in his left leg and mild back
      pain. Magnetic resonance imaging (MRI) revealed an intraspinal extradural cystic
      mass with low signal intensity on T1-weighted images and high signal intensity on
      T2-weighted images at the L5-S1 level. The partial hemilaminectomy and cyst
      resection were performed. We report a patient with low back pain and radiating
      leg pain caused by a lumbar discal cyst and discuss the treatment of this cyst.

PMID- 19096690
TI  - Lumbar spinal extradural angiolipoma: case report and review of the literature.
AB  - Angiolipomas in the lumbar spinal region are extremely rare. The present report
      describes the identification of such a tumor and its removal, and discusses the
      tumor characteristics and prognosis. A 74-year-old woman was presented with a 5
      month history of lower back pain. Severe radiculopathy was experienced in the
      left leg for 5 days prior to the presentation, and there were no neurological
      deficits. Magnetic resonance (MR) images showed an approximately 3.5 cm
      heterogeneously enhanced and elongated mass at the left L5-S1 level. A portion of
      the mass appeared with high signal intensity on T2-weighted MR images, with low
      signal intensity on T1-weighted images, and with high signal intensity on T1 fat
      suppression enhancement images. Resection of the tumor was approached via an L5
      and S1 laminectomy. A fibrous sticky yellowish hypervascular tumor was
      identified. Histological study revealed the tumor as an angiolipoma. Symptoms
      were relieved after tumor excision, and there were no neurological sequelae.
      Although extremely rare, lumbar epidural angiolipoma should be considered in the
      differential diagnosis of lumbar spinal epidural lesions. The prognosis after
      surgical management of this lesion is favorable.

PMID- 19096691
TI  - Endolymphatic sac tumors : report of four cases.
AB  - Endolymphatic sac tumor is rare, locally aggressive hypervascular tumor of
      papillary structure, arising from the endolymphatic duct or sac in the posterior
      petrous bone. We present four cases with this tumor. Two patients were male and
      the other two were female. Age of each patient was 15, 52, 58, and 67 years.
      Three patients presented with progressive hearing loss and sustained vertigo for
      months to years and another one was referred for the tumor detected in routine
      medical check-up. Preoperative embolization was performed in 3 patients. Complete
      excision of the tumor was achieved in all patients using translabyrinthine or
      retrosigmoid approach. Herein, we describe the clinical and radiographic
      features, surgical treatment and pathologic findings with a review of the
      literature.

PMID- 19096692
TI  - Skull base invasion of adenoid cystic carcinoma of the lacrimal gland : a case
      report.
AB  - Although adenoid cystic carcinoma (ACC) of the lacrimal gland is a rarely
      encountered orbital tumor, it invades intracranially more frequently than
      carcinomas of other glands in the head and neck. A 52-year-old man underwent
      orbital exenteration and resection of intracranially extended tumor via a fronto
      orbito-zygomatic approach in combination with a transfacial approach.
      Histopathologically, the tumor showed perineural, vascular, and lymphatic
      invasion. Additionally, he received radiotherapy (60 Gy) and adjuvant systemic
      cisplatin and 5-fluorouracil chemotherapy due to residual tumor in the orbit and
      systemic metastases (lung, ribs, and spines). He was free of progression and
      recurrence at 6 months after treatment. The authors report a case of skull base
      invasion by an ACC of the lacrimal gland to remind neurosurgeons planning
      intervention that this disease shows a tendency to invade intracranially.

PMID- 19096693
TI  - Brucellar spondylitis.
AB  - The incidence of Brucellosis is increasing in Korea. Spondylitis is the most
      frequent complication, but it is difficult to diagnose because its clinical
      symptoms are non-specific. It should therefore be included in the differential
      diagnosis of back pain. We report three rare cases of brucellar spondylitis
      successfully treated by medical and surgical therapy.

PMID- 19096695
TI  - Preliminary report of multisession gamma knife radiosurgery for benign perioptic
      lesions: visual outcome in 22 patients.
AB  - OBJECTIVE: Radiosurgery may be contraindicated for lesions adjacent to the optic
      pathways because of the substantial risk of visual complication. Multisession
      radiosurgery has been tried as a compromise between single session radiosurgery
      and fractionated radiotherapy. The purpose of this study is to evaluate the
      outcomes of multisession gamma knife radiosurgery (GKRS) in 22 patients with
      perioptic lesions of benign pathology. METHODS: In all 22 cases, the lesions were
      within 1 mm of the optic apparatus and were therefore not considered suitable for
      single session radiosurgery. Radiation was delivered in 3 to 4 fractions with a
      median cumulated marginal dose of 20 Gy (range, 15-20 Gy). RESULTS: During a mean
      follow-up of 29 months (range, 14-44 months), tumor control was achieved in 21
      patients. Visual function improved in 7 patients, remained unchanged in 14
      patients, and deteriorated in 1 patient with tumor progression. No other
      complication was observed. CONCLUSION: This preliminary result supports the idea
      that multisession GKRS may be an effective and safe alternative for treatment in
      perioptic lesions that are unsuitable for single session radiosurgery.

PMID- 19096694
TI  - Is Transcranial Doppler Ultrasonography Old-fashioned?: One Institutional
      Validity Study.
AB  - OBJECTIVE: The purpose of this study is to investigate the correlation between
      various transcranial Doppler (TCD) ultrasonography parameters and clinical
      vasospasm after aneurysmal subarachnoid hemorrhage (SAH). METHODS: This study
      enrolled 40 patients presented with aneurysmal SAH between September 2006 and
      August 2007. We measured differences of mean blood flow velocity (BFVm), highest
      systolic blood flow velocity (BFVh), and Lindegaard ratio (LR) in the middle
      cerebral artery on TCD examination. These parameters were evaluated for
      correlation with clinical vasospasm by univariate analysis and the receiver
      operating characteristic analysis. RESULTS: Twelve patients (30%) developed
      clinical vasospasm. The best TCD parameters for the detection of clinical
      vasospasm were revealed to be differences of BFVm, BFVh, and LR values between
      1(st) TCD test and 3(rd) TCD (7 cm/s, 11.5 cm/s, 0.45 respectively). The positive
      predictive value of any one of three parameters was 60% and the negative
      predictive value was 100%. CONCLUSION: TCD is still considered a useful tool for
      screening clinical vasospasm. To confirm the predictive value of the above
      parameters, further prospective study will be needed.

PMID- 19096696
TI  - Surgical treatment of primary spinal tumors in the conus medullaris.
AB  - OBJECTIVE: The objective of this study was to evaluate the characteristics and
      surgical outcome of the conus medullaris tumors. METHODS: We retrospectively
      reviewed 26 patients who underwent surgery for conus medullaris tumor from August
      1986 to July 2007. We analyzed clinical manifestation, preoperative MRI findings,
      extent of surgical resection, histopathologic type, adjuvant therapy, and
      outcomes. RESULTS: There were ependymoma (13), hemangioblastoma (3), lipoma (3),
      astrocytoma (3), primitive neuroectodermal tumor (PNET) (2), mature teratoma (1),
      and capillary hemangioma (1) on histopathologic type. Leg pain was the most
      common symptom and was seen in 80.8% of patients. Pain or sensory change in the
      saddle area was seen in 50% of patients and 2 patients had severe pain in the
      perineum and genitalia. Gross total or complete tumor resection was obtained in
      80.8% of patients. On surgical outcome, modified JOA score worsened in 26.9% of
      patients, improved in 34.6%, and remained stable in 38.5%. The mean VAS score was
      improved from 5.4 to 1.8 among 21 patients who had lower back pain and leg pain.
      CONCLUSION: The surgical outcome of conus medullaris tumor mainly depends on
      preoperative neurological condition and pathological type. The surgical treatment
      of conus medullaris tumor needs understanding the anatomical and functional
      characteristics of conus meudllaris tumor for better outcome.

PMID- 19096697
TI  - A morphometric study on cadaveric aortic arch and its major branches in 25 korean
      adults : the perspective of endovascular surgery.
AB  - OBJECTIVE: To understand the anatomic characteristics of the aortic arch (AA) and
      its major branches to build a foundation toward performing endovascular surgery
      safely. METHODS: A total of 25 formalin fixed Korean adult cadavers were used.
      The authors investigated : anatomical variations of the AA and its major
      branches; curvature of the AA; distance from the mid-vertebrae line to the origin
      of the major branches; distances from the origin of the major branches of AA to
      the origin of its distal branches; and the angle of the three major branches, the
      brachiocephalic trunk (BCT), the left common carotid artery (LCCA) and the left
      subclavian artery (LSCA) arising from AA. RESULTS: The three major branches
      directly originated from AA in 21 (84%) of the cadavers. In two (8%) of remaining
      four cadavers, orifice of LCCA was slightly above the stem of BCT. In remaining
      two (8%) cadavers, the left vertebral artery (LVA) was directly originated from
      AA. Average angle of AA curvature to the coronal plane was 62.2 degrees. BCT
      originated 0.92 mm on the right of the mid-vertebrae line. LCCA and LSCA
      originated from 12.3 mm and 22.8 mm on the left of the mid-vertebrae line. Mean
      distance from the origin of the BCT to the origin of the RCCA was 32.5 mm. Mean
      distance from the origin of the LSCA to the origin of the LVA was 33.8 mm.
      Average angles at which the major branches arise from the AA were 65.3, 46.9 and
      63.8 degrees. CONCLUSION: This study may provides a basic anatomical information
      to catheterize AA and its branches for safely performing endovascular surgery.

PMID- 19096698
TI  - Spontaneous spinal epidural hematoma in an infant : a case report and review of
      the literature.
AB  - Spontaneous spinal epidural hematoma (SSEH) is rare in children, especially in
      infants, in whom only 12 cases have been reported. Because of the nonspecificity
      of presenting symptoms in children, the diagnosis may be delayed. We report
      herein a case of SSEH in a 20-month-old girl who initially presented with neck
      pain, and developed lower extremity motor weakness and symptoms of neurogenic
      bladder 2 weeks prior to admission. The magnetic resonance imaging showed an
      epidural mass lesion extending from C7 to T4, and the spinal cord was severely
      compressed by the mass. After emergency decompressive surgery the neurologic
      function was improved immediately. Two months after surgery, the neurological
      status was normal with achievement of spontaneous voiding. We suggest that
      surgical intervention can provide excellent prognosis in case of SSEH in infants,
      even if surgery delayed.

PMID- 19096699
TI  - Cavernous malformation of the optic chiasm : case report.
AB  - Cavernous malformations (CMs) arising from the optic nerve and chiasm are
      extremely rare. The authors present a case of 39-year-old woman with CMs of the
      optic chiasm. She was referred due to sudden onset of bitemporal hemianopsia and
      headache, the so-called 'chiasmal apoplexy'. MRI findings suggested a diagnosis
      of hemorrhage and vascular malformation of the optic chiasm. Pterional craniotomy
      revealed an intrachiasmatic cavernous malformation with hemorrhage. The
      malformation was totally excised, but field deficits remained unchanged after
      surgery.

PMID- 19096700
TI  - Primary paraspinal malignant peripheral nerve sheath tumor.
AB  - Malignant peripheral nerve sheath tumors (MPNSTs) are very rare tumors. We
      experienced a case of MPNST in the cervical paraspinal space which was not
      associated with neurofibromatosis. The tumor located in left C6-7 foramen and
      compressed C7 root. The tumor was removed through the occipital triangle. We
      report a case of the primary cerivcal MPNST in a patient who did not have
      neurofibromatosis-1.

PMID- 19096701
TI  - Intraventricular and subarachnoid fat after spinal injury.
AB  - The authors report an extremely rare case with intraventricular and subarachnoid
      fat developed after trauma to spine and soft tissue in a 54-year-old male. The
      initial computed tomography (CT) showed multiple low attenuation lesions, which
      were thought to be pneumocephalus. Cerebral magnetic resonance imaging (MRI)
      showed lesions with high signal intensity on T1-weighted magnetic resonance
      images and high signal intensity on T2-weighted images, indicating fat globules
      within the CSF. In this report, the clinical presentation, radiological findings,
      and a review of the literature are presented.

PMID- 19096702
TI  - Rapidly calcified epidural hematoma in a neonate.
AB  - We report a very rare case of a rapidly calcified chronic epidural hematoma (EDH)
      in a neonate. A 26-day-old female infant was referred to us from a regional
      hospital because of drowsy mentality and a seizure attack. She was delivered
      through caesarian section because normal spontaneous vaginal delivery was
      prolonged and failed. At birth, mild scalp swelling was found on the right
      frontal area. Scalp swelling was spontaneously resolved and she was discharged
      without any problems. On the 25th day after her birth, the baby presented with
      drowsiness and hypotonia following a generalized tonic-clonic seizure. Magnetic
      resonance imaging (MRI) and a computed tomography (CT) scan revealed a chronic
      EDH that had a thick layer of calcification. A small burr-hole trephination was
      performed and a single silastic drainage catheter was inserted. After the
      operation, a total of 12 ml of liquefied hematoma was drained, and the patient's
      mentality improved from drowsiness to alertness. The patient was asymptomatic
      when discharged.

PMID- 19096703
TI  - Intracranial pial arteriovenous fistulas.
AB  - Intracranial pial arteriovenous fistula (AVF) is a rare cerebrovascular lesion
      that has only recently been recognized as a distinct pathological entity. A 41
      year-old woman (Patient 1) presented with the sudden development of an altered
      mental state. Brain CT showed an acute subdural hematoma. A red sylvian vein was
      found intraoperatively. A pial AVF was revealed on postoperative angiography, and
      surgical disconnection of the AVF was performed. A 10-year-old boy (Patient 2)
      presented with a 10-day history of paraparesis and urinary incontinence. Brain,
      spinal MRI and angiography revealed an intracranial pial AVF and a spinal
      perimedullary AVF. Endovascular embolization was performed for both lesions. The
      AVFs were completely obliterated in both patients. On follow-up, patient 1
      reported having no difficulty in performing activities of daily living. Patient 2
      is currently able to walk without assistance and voids into a diaper.
      Intracranial pial AVF is a rare disease entity that can be treated with surgical
      disconnection or endovascular embolization. It is important for the appropriate
      treatment strategy to be selected on the basis of patientspecific and lesion
      specific factors in order to achieve good outcomes.

PMID- 19096704
TI  - Interpersonal trust and quality-of-life: a cross-sectional study in Japan.
AB  - BACKGROUND: There is growing interest in psychosocial factors with positive
      attitudes, such as interpersonal trust, as determinants for Quality-of-life (QOL)
      or subjective well-being. Despite their longevity, Japanese people report a
      relatively poor subjective well-being, as well as lower interpersonal trust. Our
      aim in this study was to evaluate the possible association between interpersonal
      trust and QOL among Japanese people. METHODOLOGY AND PRINCIPAL FINDINGS: Based on
      the cross-sectional data for Japanese adults (2008), we analyzed the relationship
      between interpersonal trust and each of four domains of the WHOQOL-BREF.
      Interpersonal trust was assessed using three scales for trust in people, in human
      fairness and in human nature. In a total of 1000 participants (mean age: 45
      years; 49% women), greater trust was recognized among women (vs. men), those aged
      60-69 (vs. 20-29), or the high-income group (vs. low-income). Each of three trust
      scales was positively correlated with all domains of QOL. Multiple linear
      regression models were constructed for each of QOL and the principal component
      score of the trust scales, adjusted for age, gender, area size of residence,
      income, education, and occupation. For all QOL domains, interpersonal trust was
      significantly and positively associated with better QOL with p<0.001 for all four
      domains including physical, psychological, social, and environmental QOL. Other
      factors associated with QOL included gender, age class, area size of residence,
      and income. Education and occupation were not associated with QOL. CONCLUSIONS
      AND SIGNIFICANCE: Greater interpersonal trust is strongly associated with a
      better QOL among Japanese adults. If a causal relationship is demonstrated in a
      controlled interventional study, social and political measures should be
      advocated to increase interpersonal trust for achieving better QOL.

PMID- 19096705
TI  - Physcomitrella patens DCL3 is required for 22-24 nt siRNA accumulation,
      suppression of retrotransposon-derived transcripts, and normal development.
AB  - Endogenous 24 nt short interfering RNAs (siRNAs), derived mostly from intergenic
      and repetitive genomic regions, constitute a major class of endogenous small RNAs
      in flowering plants. Accumulation of Arabidopsis thaliana 24 nt siRNAs requires
      the Dicer family member DCL3, and clear homologs of DCL3 exist in both flowering
      and non-flowering plants. However, the absence of a conspicuous 24 nt peak in the
      total RNA populations of several non-flowering plants has raised the question of
      whether this class of siRNAs might, in contrast to the ancient 21 nt microRNAs
      (miRNAs) and 21-22 nt trans-acting siRNAs (tasiRNAs), be an angiosperm-specific
      innovation. Analysis of non-miRNA, non-tasiRNA hotspots of small RNA production
      within the genome of the moss Physcomitrella patens revealed multiple loci that
      consistently produced a mixture of 21-24 nt siRNAs with a peak at 23 nt. These
      Pp23SR loci were significantly enriched in transposon content, depleted in
      overlap with annotated genes, and typified by dense concentrations of the 5
      methyl cytosine (5 mC) DNA modification. Deep sequencing of small RNAs from two
      independent Ppdcl3 mutants showed that the P. patens DCL3 homolog is required for
      the accumulation of 22-24 nt siRNAs, but not 21 nt siRNAs, at Pp23SR loci. The 21
      nt component of Pp23SR-derived siRNAs was also unaffected by a mutation in the
      RNA-dependent RNA polymerase mutant Pprdr6. Transcriptome-wide, Ppdcl3 mutants
      failed to accumulate 22-24 nt small RNAs from repetitive regions while
      transcripts from two abundant families of long terminal repeat (LTR)
      retrotransposon-associated reverse transcriptases were up-regulated. Ppdcl3
      mutants also displayed an acceleration of leafy gametophore production,
      suggesting that repetitive siRNAs may play a role in the development of P.
      patens. We conclude that intergenic/repeat-derived siRNAs are indeed a broadly
      conserved, distinct class of small regulatory RNAs within land plants.

PMID- 19096706
TI  - Developmental constraints on vertebrate genome evolution.
AB  - Constraints in embryonic development are thought to bias the direction of
      evolution by making some changes less likely, and others more likely, depending
      on their consequences on ontogeny. Here, we characterize the constraints acting
      on genome evolution in vertebrates. We used gene expression data from two
      vertebrates: zebrafish, using a microarray experiment spanning 14 stages of
      development, and mouse, using EST counts for 26 stages of development. We show
      that, in both species, genes expressed early in development (1) have a more
      dramatic effect of knock-out or mutation and (2) are more likely to revert to
      single copy after whole genome duplication, relative to genes expressed late.
      This supports high constraints on early stages of vertebrate development, making
      them less open to innovations (gene gain or gene loss). Results are robust to
      different sources of data -- gene expression from microarrays, ESTs, or in situ
      hybridizations; and mutants from directed KO, transgenic insertions, point
      mutations, or morpholinos. We determine the pattern of these constraints, which
      differs from the model used to describe vertebrate morphological conservation
      ("hourglass" model). While morphological constraints reach a maximum at mid
      development (the "phylotypic" stage), genomic constraints appear to decrease in a
      monotonous manner over developmental time.

PMID- 19096707
TI  - Novel low abundance and transient RNAs in yeast revealed by tiling microarrays
      and ultra high-throughput sequencing are not conserved across closely related
      yeast species.
AB  - A complete description of the transcriptome of an organism is crucial for a
      comprehensive understanding of how it functions and how its transcriptional
      networks are controlled, and may provide insights into the organism's evolution.
      Despite the status of Saccharomyces cerevisiae as arguably the most well-studied
      model eukaryote, we still do not have a full catalog or understanding of all its
      genes. In order to interrogate the transcriptome of S. cerevisiae for low
      abundance or rapidly turned over transcripts, we deleted elements of the RNA
      degradation machinery with the goal of preferentially increasing the relative
      abundance of such transcripts. We then used high-resolution tiling microarrays
      and ultra high-throughput sequencing (UHTS) to identify, map, and validate
      unannotated transcripts that are more abundant in the RNA degradation mutants
      relative to wild-type cells. We identified 365 currently unannotated transcripts,
      the majority presumably representing low abundance or short-lived RNAs, of which
      185 are previously unknown and unique to this study. It is likely that many of
      these are cryptic unstable transcripts (CUTs), which are rapidly degraded and
      whose function(s) within the cell are still unclear, while others may be novel
      functional transcripts. Of the 185 transcripts we identified as novel to our
      study, greater than 80 percent come from regions of the genome that have lower
      conservation scores amongst closely related yeast species than 85 percent of the
      verified ORFs in S. cerevisiae. Such regions of the genome have typically been
      less well-studied, and by definition transcripts from these regions will
      distinguish S. cerevisiae from these closely related species.

PMID- 19096708
TI  - Ixodes ricinus tick lipocalins: identification, cloning, phylogenetic analysis
      and biochemical characterization.
AB  - BACKGROUND: During their blood meal, ticks secrete a wide variety of proteins
      that interfere with their host's defense mechanisms. Among these proteins,
      lipocalins play a major role in the modulation of the inflammatory response.
      METHODOLOGY/PRINCIPAL FINDINGS: Screening a cDNA library in association with RT
      PCR and RACE methodologies allowed us to identify 14 new lipocalin genes in the
      salivary glands of the Ixodes ricinus hard tick. A computational in-depth
      structural analysis confirmed that LIRs belong to the lipocalin family. These
      proteins were called LIR for "Lipocalin from I. ricinus" and numbered from 1 to
      14 (LIR1 to LIR14). According to their percentage identity/similarity, LIR
      proteins may be assigned to 6 distinct phylogenetic groups. The mature proteins
      have calculated pM and pI varying from 21.8 kDa to 37.2 kDa and from 4.45 to 9.57
      respectively. In a western blot analysis, all recombinant LIRs appeared as a
      series of thin bands at 50-70 kDa, suggesting extensive glycosylation, which was
      experimentally confirmed by treatment with N-glycosidase F. In addition, the in
      vivo expression analysis of LIRs in I. ricinus, examined by RT-PCR, showed
      homogeneous expression profiles for certain phylogenetic groups and relatively
      heterogeneous profiles for other groups. Finally, we demonstrated that LIR6 codes
      for a protein that specifically binds leukotriene B4. CONCLUSIONS/SIGNIFICANCE:
      This work confirms that, regarding their biochemical properties, expression
      profile, and sequence signature, lipocalins in Ixodes hard tick genus, and more
      specifically in the Ixodes ricinus species, are segregated into distinct
      phylogenetic groups suggesting potential distinct function. This was particularly
      demonstrated by the ability of LIR6 to scavenge leukotriene B4. The other LIRs
      did not bind any of the ligands tested, such as 5-hydroxytryptamine, ADP,
      norepinephrine, platelet activating factor, prostaglandins D2 and E2, and finally
      leukotrienes B4 and C4.

PMID- 19096709
TI  - Improved Insulin Resistance and Lipid Metabolism by Cinnamon Extract through
      Activation of Peroxisome Proliferator-Activated Receptors.
AB  - Peroxisome proliferator-activated receptors (PPARs) are transcriptional factors
      involved in the regulation of insulin resistance and adipogenesis. Cinnamon, a
      widely used spice in food preparation and traditional antidiabetic remedy, is
      found to activate PPARgamma and alpha, resulting in improved insulin resistance,
      reduced fasted glucose, FFA, LDL-c, and AST levels in high-caloric diet-induced
      obesity (DIO) and db/db mice in its water extract form. In vitro studies
      demonstrate that cinnamon increases the expression of peroxisome proliferator
      activated receptors gamma and alpha (PPARgamma/alpha) and their target genes such
      as LPL, CD36, GLUT4, and ACO in 3T3-L1 adipocyte. The transactivities of both
      full length and ligand-binding domain (LBD) of PPARgamma and PPARalpha are
      activated by cinnamon as evidenced by reporter gene assays. These data suggest
      that cinnamon in its water extract form can act as a dual activator of PPARgamma
      and alpha, and may be an alternative to PPARgamma activator in managing obesity
      related diabetes and hyperlipidemia.

PMID- 19096710
TI  - The study of a new method to determine copper ion by square-wave voltammetry
      extraction iodometry at the liquid/liquid interfaces.
AB  - A new method of indirect determination of Cu(2+) was developed based on square
      wave voltammetry by the oxidation of iodide in organic solvent at the
      liquid/liquid (L/L) interface. The limit of detection for the determination of
      Cu(2+) in this method was found to be 5 x 10(-4) mol/L, and the concentration
      ranged up to 1 x 10(-2) mol/L gave a linear limiting current versus concentration
      response. For the same simulated wastewater, this method showed high accuracy
      compared with the result tested by sodium diethyldithiocarbamate extraction
      spectrophotometry. This approach could be applied to the indirect determination
      of the oxidative heavy metals in the industrial wastewater.

PMID- 19096712
TI  - PPARgamma, PTEN, and the Fight against Cancer.
AB  - Peroxisome proliferator-activated receptor gamma (PPARgamma) is a ligand
      activated transcription factor, which belongs to the family of nuclear hormone
      receptors. Recent in vitro studies have shown that PPARgamma can regulate the
      transcription of phosphatase and tensin homolog on chromosometen (PTEN), a known
      tumor suppressor. PTEN is a susceptibility gene for a number of disorders,
      including breast and thyroid cancer. Activation of PPARgamma through agonists
      increases functional PTEN protein levels that subsequently induces apoptosis and
      inhibits cellular growth, which suggests that PPARgamma may be a tumor
      suppressor. Indeed, several in vivo studies have demonstrated that genetic
      alterations of PPARgamma can promote tumor progression. These results are
      supported by observations of the beneficial effects of PPARgamma agonists in the
      in vivo cancer setting. These studies signify the importance of PPARgamma and
      PTEN's interaction in cancer prevention.

PMID- 19096711
TI  - Steady state bioequivalence of generic and innovator formulations of stavudine,
      lamivudine, and nevirapine in HIV-infected Ugandan adults.
AB  - BACKGROUND: Generic antiretroviral therapy is the mainstay of HIV treatment in
      resource-limited settings, yet there is little evidence confirming the
      bioequivalence of generic and brand name formulations. We compared the steady
      state pharmacokinetics of lamivudine, stavudine and nevirapine in HIV-infected
      subjects who were receiving a generic formulation (Triomune) or the corresponding
      brand formulations (Epivir, Zerit, and Viramune). METHODOLOGY/PRINCIPAL FINDINGS:
      An open-label, randomized, crossover study was carried out in 18 HIV-infected
      Ugandan subjects stabilized on Triomune-40. Subjects received lamivudine (150
      mg), stavudine (40 mg), and nevirapine (200 mg) in either the generic or brand
      formulation twice a day for 30 days, before switching to the other formulation.
      At the end of each treatment period, blood samples were collected over 12 h for
      pharmacokinetic analysis. The main outcome measures were the mean AUC(0-12h) and
      C(max). Bioequivalence was defined as a geometric mean ratio between the generic
      and brand name within the 90% confidence interval of 0.8-1.25. The geometric mean
      ratios and the 90% confidence intervals were: stavudine C(max), 1.3 (0.99-1.71)
      and AUC(0-12h), 1.1 (0.87-1.38); lamivudine C(max), 0.8 (0.63-0.98) and AUC(0
      12h), 0.8 (0.65-0.99); and nevirapine C(max), 1.1 (0.95-1.23) and AUC(0-12h), 1.1
      (0.95-1.31). The generic formulation was not statistically bioequivalent to the
      brand formulations during steady state, although exposures were comparable. A
      mixed random effects model identified about 50% intersubject variability in the
      pharmacokinetic parameters. CONCLUSIONS/SIGNIFICANT FINDINGS: These findings
      provide support for the use of Triomune in resource-limited settings, although
      identification of the sources of intersubject variability in these populations is
      critical.

PMID- 19096713
TI  - The effect of patient arrival time on overall wait time and utilization of
      physician and examination room resources in the outpatient urology clinic.
AB  - Introduction and objective. We examined patient waiting times, physician
      utilization, and exam room utilization in order to identify process improvements
      that may improve patient satisfaction. Methods. Time patient arrived to clinic,
      time patient was placed in the exam room, time the physician arrived in the exam
      room, and time physician discharged the patient from the exam room were
      prospectively recorded for 226 outpatient visits. Results. Overall, 63.2% of
      patients were on time for their scheduled appointment with 14.8% patient "no
      shows." On-time patients were found to have a longer wait time once in the exam
      room for the physician than those that were late (14.8 +/- 9.2 minutes versus
      11.0 +/- 8.4 minutes, P = .005); however, those patients spent a significantly
      longer time with the physician (10.7 +/- 6.0 minutes versus 8.9 +/- 5.8 minutes,
      P = .041). Exam room utilization was lower for late patients (28.9% versus 44.7%,
      P = .03) with physician utilization lower in clinics with 3 or more late patients
      when compared to clinics with 2 or fewer (59.7% versus 68.7%, P = .004).
      Conclusions. Late patients had significantly less time with the physician than on
      time patients. Late patients also decreased the overall efficiency of the clinic;
      therefore, measures to reduce late patients are vital to improve clinic
      efficiency.

PMID- 19096714
TI  - Never resting brain: simultaneous representation of two alpha related processes
      in humans.
AB  - Brain activity is continuously modulated, even at "rest". The alpha rhythm (8-12
      Hz) has been known as the hallmark of the brain's idle-state. However, it is
      still debated if the alpha rhythm reflects synchronization in a distributed
      network or focal generator and whether it occurs spontaneously or is driven by a
      stimulus. This EEG/fMRI study aimed to explore the source of alpha modulations
      and their distribution in the resting brain. By serendipity, while computing the
      individually defined power modulations of the alpha-band, two simultaneously
      occurring components of these modulations were found. An 'induced alpha' that was
      correlated with the paradigm (eyes open/ eyes closed), and a 'spontaneous alpha'
      that was on-going and unrelated to the paradigm. These alpha components when used
      as regressors for BOLD activation revealed two segregated activation maps: the
      'induced map' included left lateral temporal cortical regions and the
      hippocampus; the 'spontaneous map' included prefrontal cortical regions and the
      thalamus. Our combined fMRI/EEG approach allowed to computationally untangle two
      parallel patterns of alpha modulations and underpin their anatomical basis in the
      human brain. These findings suggest that the human alpha rhythm represents at
      least two simultaneously occurring processes which characterize the 'resting
      brain'; one is related to expected change in sensory information, while the other
      is endogenous and independent of stimulus change.

PMID- 19096715
TI  - Reordering for improved constrained reconstruction from undersampled k-space
      data.
AB  - Recently, there has been a significant interest in applying reconstruction
      techniques, like constrained reconstruction or compressed sampling methods, to
      undersampled k-space data in MRI. Here, we propose a novel reordering technique
      to improve these types of reconstruction methods. In this technique, the
      intensities of the signal estimate are reordered according to a preprocessing
      step when applying the constraints on the estimated solution within the iterative
      reconstruction. The ordering of the intensities is such that it makes the
      original artifact-free signal monotonic and thus minimizes the finite differences
      norm if the correct image is estimated; this ordering can be estimated based on
      the undersampled measured data. Theory and example applications of the method for
      accelerating myocardial perfusion imaging with respiratory motion and brain
      diffusion tensor imaging are presented.

PMID- 19096716
TI  - The Potential Applications of Peroxisome Proliferator-Activated Receptor delta
      Ligands in Assisted Reproductive Technology.
AB  - Peroxisome proliferator-activated receptor delta (PPARdelta, also known as
      PPARbeta) has ubiquitous distribution and extensive biological functions. The
      reproductive function of PPARdelta was first revealed in the uterus at the
      implantation site. Since then, PPARdelta and its ligand have been discovered in
      all reproductive tissues, including the gametes and the preimplantation embryos.
      PPARdelta in preimplantation embryos is normally activated by oviduct-derived
      PPARdelta ligand. PPARdelta activation is associated with an increase in
      embryonic cell proliferation and a decrease in programmed cell death (apoptosis).
      On the other hand, the role of PPARdelta and its ligand in gamete formation and
      function is less well understood. This review will summarize the reproductive
      functions of PPARdelta and project its potential applications in assisted
      reproductive technology.

PMID- 19096717
TI  - Voltage-dependent Ca2+ channels, not ryanodine receptors, activate Ca2+-dependent
      BK potassium channels in human retinal pigment epithelial cells.
AB  - PURPOSE: In different tissues the activation of large conductance Ca2+-activated
      (BK) potassium channels has been shown to be coupled to voltage-gated Ca2+
      channels as well as ryanodine receptors. As activation of BK channels leads to
      hyperpolarization of the cell, these channels provide a negative feedback
      mechanism for Ca2+-induced functions. Many cellular functions of the retinal
      pigment epithelium (RPE) are coupled to changes in [Ca2+]i. The aim of this study
      was to identify which Ca2+-entry pathway leads to the activation of BK channels
      in the RPE. METHODS: We used freshly isolated human RPE cells and the ARPE-19
      cell line for the detection of transcripts of BK channel alpha subunits. Patch
      Clamp measurements were used to characterize BK channels in ARPE-19 cells
      electrophysiologically. To monitor changes in [Ca2+]i ARPE-19 cells were loaded
      with Fura-2. RESULTS: Freshly isolated human RPE cells and ARPE-19 cells were
      shown to express BK channels. In ARPE-19 cells these channels were shown to be
      functionally active. Application of iberiotoxin led to a block of outward
      currents by 28.15%. At +50 mV ARPE-19 cells had a BK channel-mediated current
      density of 2.42 pA/pF. Activation of ryanodine receptors by caffeine led to a
      significant increase in [Ca2+]i by 34.16%. Nevertheless, caffeine-induced Ca2+
      signals were not sufficient to activate BK channels. Instead, the activation of L
      type Ca2+ channels by BayK 8644 caused a dramatic increase in BK channel activity
      and a shift of the reversal potential of the ARPE-19 cells by -22.6 mV.
      CONCLUSIONS: We have shown here for the first time that human RPE cells express
      BK channels. These channels are activated in RPE cells by increases in [Ca2+]i
      that are mediated by the opening of voltage gated L-type Ca2+ channels. As Ca2+
      entering the RPE cells through these Ca2+ channels are known to be important for
      growth factor secretion and light-induced transepithelial transport, we speculate
      that BK channels coupled directly to these Ca2+ channels may provide a good tool
      for negative feedback control of the L-type Ca2+ channels.

PMID- 19096718
TI  - Screening of common CYP1B1 mutations in Iranian POAG patients using a microarray
      based PrASE protocol.
AB  - PURPOSE: The gene coding cytochrome P4501B1 (CYP1B1) has been shown to be a major
      cause of primary congenital glaucoma in the Iranian population. More recently it
      was shown to also be important in juvenile-onset open angle glaucoma (JOAG). We
      aimed to further investigate the role of CYP1B1 in a larger cohort of primary
      open angle glaucoma (POAG) patients which included late-onset patients. We also
      aimed to set up a microarray based protocol for mutation screening with an intent
      of using the protocol in a future population level screening program. METHODS:
      Sixty three POAG patients, nine affected family members, and thirty three
      previously genotyped primary congenital glaucoma (PCG) patients were included in
      the study. Clinical examination included slit lamp biomicroscopy, IOP
      measurement, gonioscopic evaluation, fundus examination, and measurement of
      perimetry. G61E, R368H, R390H, and R469W were screened by a protocol that
      included multiplexed allele specific amplification in the presence of a protease
      (PrASE), use of sequence tagged primers, and hybridization to generic arrays on
      microarray slides. The entire coding sequences of CYP1B1 and myocilin (MYOC)
      genes were sequenced in all individuals assessed by the microarray assay to carry
      a mutation. Intragenic single nucleotide polymorphism (SNP) haplotpes were
      determined for mutated alleles. RESULTS: Genotypes assessed by the array-based
      PrASE methodology were in 100% concordance with sequencing results. Seven
      mutation carrying POAG patients (11.1%) were identified, and their distribution
      was quite skewed between the juvenile-onset individuals (5/21) as compared to
      late-onset cases (2/42). Four of the seven mutation carrying Iranian patients
      harbored two mutated alleles. CYP1B1 mutated alleles in Iranian PCG and POAG
      patients shared common haplotypes. MYOC mutations were not observed in any of the
      patients. CONCLUSIONS: The PrASE approach allowed reliable simultaneous
      genotyping of many individuals. It can be an appropriate tool for screening
      common mutations in large sample sizes. The results suggest that CYP1B1 is
      implicated in POAG among Iranians, notably in the juvenile-onset form. Contrary
      to POAG patients studied in other populations, many mutation harboring Iranian
      patients carry two mutated alleles. We propose an explanation for this
      observation.

PMID- 19096720
TI  - A nitrile hydratase in the eukaryote Monosiga brevicollis.
AB  - Bacterial nitrile hydratase (NHases) are important industrial catalysts and waste
      water remediation tools. In a global computational screening of conventional and
      metagenomic sequence data for NHases, we detected the two usually separated NHase
      subunits fused in one protein of the choanoflagellate Monosiga brevicollis, a
      recently sequenced unicellular model organism from the closest sister group of
      Metazoa. This is the first time that an NHase is found in eukaryotes and the
      first time it is observed as a fusion protein. The presence of an intron, subunit
      fusion and expressed sequence tags covering parts of the gene exclude
      contamination and suggest a functional gene. Phylogenetic analyses and genomic
      context imply a probable ancient horizontal gene transfer (HGT) from
      proteobacteria. The newly discovered NHase might open biotechnological routes due
      to its unconventional structure, its new type of host and its apparent
      integration into eukaryotic protein networks.

PMID- 19096721
TI  - An analysis pipeline for genome-wide association studies.
AB  - We developed an efficient pipeline to analyze genome-wide association study
      single nucleotide polymorphism scan results. Purl scripts were used to convert
      genotypes called using the BRLMM algorithm into a modified PB format. We computed
      summary statistics characteristic of our case and control populations including
      allele counts, missing values, heterozygosity, measures of compliance with Hardy
      Weinberg equilibrium, and several population difference statistics. In addition,
      we computed association tests, including exact tests of association for
      genotypes, alleles, the Cochran-Armitage linear trend test, and dominant,
      recessive, and over dominant models at every single nucleotide polymorphism
      (SNP). In addition, pairwise linkage disequilibrium statistics were elaborated,
      using the command line version of HaploView, which was possible by writing a
      reformatting script. Additional Perl scripts permit loading the results into a
      MySQL database conjoined with a Generic Genome Browser (gbrowse) for
      comprehensive visualization. This browser incorporates a download feature that
      provides actual case and control genotypes to users in associated genomic
      regions. Thus, re-analysis "on the fly" is possible for casual browser users from
      anywhere on the Internet.

PMID- 19096722
TI  - Acute Kidney Injury Biomarkers - Needs, Present Status, and Future Promise.

PMID- 19096719
TI  - Evaluation of splicing efficiency in lymphoblastoid cell lines from patients with
      splicing-factor retinitis pigmentosa.
AB  - PURPOSE: Retinitis pigmentosa (RP) is caused by mutations in a variety of genes,
      most of which have known functions in the retina. However, one of the most
      perplexing findings of recent retinal genetics research was the discovery of
      mutations causing dominant RP in four ubiquitously expressed splicing factors.
      The aim of this study was to use lymphoblast cell lines derived from RP patients
      to determine whether mutations in two of these splicing factors, PRPF8 and
      PRPF31, cause measurable deficiencies in pre-mRNA splicing. METHODS: cDNA was
      prepared from lymphoblastoid cell lines derived from RP patients bearing
      mutations in the splicing factor genes and controls, grown under a variety of
      conditions. Introns representing the U2 and U12 intron classes, with both
      canonical and noncanonical donor and acceptor sequences, were analyzed by real
      time PCR to measure the ratio of spliced versus unspliced transcripts for these
      introns. In addition, plasmids encoding the retinal outer segment membrane
      protein-1 (ROM-1; exon 1 to exon 2) gene, both in the wild-type form and with
      mutations introduced into the splice donor sites, were transfected into cell
      lines. The spliced versus unspliced cDNA ratios were measured by real-time RT
      PCR. RESULTS: Splicing of four canonical U2 introns in the actin beta (ACTB),
      glyceraldehyde-3-phosphate dehydrogenase (GAPDH), PRPF8, and retinitis pigmentosa
      GTPase regulator (RPGR) genes was unaffected in PRPF8 mutant cells. However, the
      splicing efficiency of RPGR intron 9 was significantly decreased in PRPF31 mutant
      cell lines. In contrast, a consistent decrease in the splicing efficiency of all
      U12 and noncanonical U2 introns was seen in PRPF8, but not in PRPF31, mutant
      cells, with statistical significance for STK11 intron 3. CONCLUSIONS: In spite of
      the ubiquitous expression patterns of the genes implicated in splicing factor RP,
      no pathology has yet been documented outside the retina. The observed differences
      in splicing efficiency described herein favor the hypothesis that these mutations
      may have a subpathological effect outside the retina. These observations argue
      against a defect in some yet to be discovered additional function of these
      proteins and support the alternative hypothesis that this form of RP does indeed
      result from aberrant splicing of retinal transcripts.

PMID- 19096723
TI  - Causal Vaccine Effects on Binary Postinfection Outcomes.
AB  - The effects of vaccine on postinfection outcomes, such as disease, death, and
      secondary transmission to others, are important scientific and public health
      aspects of prophylactic vaccination. As a result, evaluation of many vaccine
      effects condition on being infected. Conditioning on an event that occurs
      posttreatment (in our case, infection subsequent to assignment to vaccine or
      control) can result in selection bias. Moreover, because the set of individuals
      who would become infected if vaccinated is likely not identical to the set of
      those who would become infected if given control, comparisons that condition on
      infection do not have a causal interpretation. In this article we consider
      identifiability and estimation of causal vaccine effects on binary postinfection
      outcomes. Using the principal stratification framework, we define a postinfection
      causal vaccine efficacy estimand in individuals who would be infected regardless
      of treatment assignment. The estimand is shown to be not identifiable under the
      standard assumptions of the stable unit treatment value, monotonicity, and
      independence of treatment assignment. Thus selection models are proposed that
      identify the causal estimand. Closed-form maximum likelihood estimators (MLEs)
      are then derived under these models, including those assuming maximum possible
      levels of positive and negative selection bias. These results show the relations
      between the MLE of the causal estimand and two commonly used estimators for
      vaccine effects on postinfection outcomes. For example, the usual intent-to-treat
      estimator is shown to be an upper bound on the postinfection causal vaccine
      effect provided that the magnitude of protection against infection is not too
      large. The methods are used to evaluate postinfection vaccine effects in a
      clinical trial of a rotavirus vaccine candidate and in a field study of a
      pertussis vaccine. Our results show that pertussis vaccination has a significant
      causal effect in reducing disease severity.

PMID- 19096724
TI  - A Comparison of African American and Cuban American Adolescent Juvenile
      Offenders: Risky Sexual and Drug Use Behaviors.
AB  - Racial and ethnic disparities exist in HIV seroconversion rates, with African
      American and Hispanic youth in the 13-19-year-old age group representing 61% and
      21% of new AIDS cases, respectively. The aim of this study was to examine sexual
      and drug use behaviors among a sample of 138 African American and Cuban American
      juvenile offenders. Cuban American adolescents showed higher levels of
      unprotected sex, higher levels of sex while using drugs, and higher levels of
      drug/alcohol use in the three and six months prior to confinement. These
      differences may be explained by multiple factors, including differences in
      acculturation levels among the Cuban American adolescents, differences in health
      messages targeted at the two groups, and family mores and norms.

PMID- 19096726
TI  - Automated trapping, assembly, and sorting with holographic optical tweezers.
AB  - We combine real-time feature recognition with holographic optical tweezers to
      automatically trap, assemble, and sort micron-sized colloidal particles. Closed
      loop control will enable new applications of optical micromanipulation in
      biology, medicine, materials science, and possibly quantum computation.

PMID- 19096727
TI  - Watching Hydrogen Bonds Break: A Transient Absorption Study of Water.
AB  - Ultrafast infrared transient absorption measurements of the complete hydroxyl OD
      stretching mode spectrum of HOD in water, from 100 fs to tens of picoseconds,
      observe hydrogen bond breaking and monitor the equilibration of the hydrogen bond
      network in water. In addition, the vibrational lifetime, the time constant for
      hydrogen bond breaking, and the rate of orientational relaxation are determined.
      The reactant and photoproduct spectra of the hydrogen bond breaking process are
      identified by decomposing the transient spectra into two components, the initial
      spectrum associated with vibrational excited states (reactants) and the long-time
      spectrum associated with broken hydrogen bonds (photoproducts). By properly
      taking into account the perturbation of the reactant spectrum decay by the growth
      of the photoproduct spectrum, it is found that the vibrational relaxation (1.45
      ps) and orientational relaxation (1.53 ps) are wavelength independent and,
      therefore, independent of the degree of hydrogen bonding. Energy deposited into
      water by vibrational relaxation does not immediately break a hydrogen bond by
      predissociation nor produce a thermally equilibrated hydrogen bond distribution
      at an elevated temperature. Following deposition of energy by vibrational
      relaxation, the hydrogen bond breaking time is 800 fs, and there is a transient
      period of several picoseconds during which the hydrogen bond distribution is not
      in thermal equilibrium.

PMID- 19096725
TI  - The Genetic Basis of HIV-1 Resistance to Reverse Transcriptase and Protease
      Inhibitors.
AB  - HIV-1 drug resistance is caused by mutations in the reverse transcriptase (RT)
      and protease enzymes, the molecular targets of antiretroviral therapy. At the
      beginning of the year 2000, two expert panels recommended that HIV-1 RT and
      protease susceptibility testing be used to help select antiretroviral drugs for
      HIV-1-infected patients. Genotypic assays have been developed to detect HIV-1
      mutations known to confer antiretroviral drug resistance. Genotypic assays using
      dideoxynucleoside sequencing provide extensive insight into the presence of drug
      resistant variants in the population of viruses within an individual. However,
      the interpretation of these assays in clinical settings is formidable because of
      the large numbers of drug resistance mutations and because these mutations
      interact with one another and emerge in complex patterns. In addition, cross
      resistance between antiretroviral drugs is greater than that anticipated from
      initial in vitro studies. This review summarises the published data linking HIV-1
      RT and protease mutations to in vitro and clinical resistance to the currently
      available nucleoside RT inhibitors, non-nucleoside RT inhibitors, and protease
      inhibitors.

PMID- 19096728
TI  - Adaptive-optics optical coherence tomography for high-resolution and high-speed
      3D retinal in vivo imaging.
AB  - We have combined Fourier-domain optical coherence tomography (FD-OCT) with a
      closed-loop adaptive optics (AO) system using a Hartmann-Shack wavefront sensor
      and a bimorph deformable mirror. The adaptive optics system measures and corrects
      the wavefront aberration of the human eye for improved lateral resolution (~4
      MUm) of retinal images, while maintaining the high axial resolution (~6 MUm) of
      stand alone OCT. The AO-OCT instrument enables the three-dimensional (3D)
      visualization of different retinal structures in vivo with high 3D resolution
      (4*4*6 MUm). Using this system, we have demonstrated the ability to image
      microscopic blood vessels and the cone photoreceptor mosaic.

PMID- 19096729
TI  - LARVAL COMPETITION DIFFERENTIALLY AFFECTS ARBOVIRUS INFECTION IN AEDES
      MOSQUITOES.
AB  - Both density-mediated and trait-mediated indirect biotic interactions may be
      important in structuring communities. Indirect interactions in many study systems
      remain unexplored; in part, because they are often difficult to detect, and in
      many instances, have been identified empirically only when unexpected results
      arise. Indirect effects induced by competition may be particularly important
      among organisms with complex life cycles, wherein competitive effects experienced
      in one life stage influence species interactions in one or more subsequent
      stages. We determined whether species-specific effects of larval competition in
      the mosquitoes Aedes albopictus and Aedes aegypti have indirect effects at the
      adult stage, specifically testing for effects on arboviral infection with Sindbis
      virus (SINV). For A. albopictus, but not for A. aegypti, competition resulted in
      greater infection, body titer, and dissemination rates compared to low
      competition conditions. Whole body titers of virus increased with adult size
      irrespective of competition. However, between competitive treatments, mosquitoes
      from low-competition conditions had greater mean size, with lower infection rates
      and lower whole body titers than the smaller mosquitoes from high-competition
      conditions. These results suggest that larval competition, common in natural
      mosquito populations, has important indirect effects on adults by altering
      mosquito-virus interactions. Such indirect effects may change transmission
      parameters of pathogens.

PMID- 19096730
TI  - High-speed volumetric imaging of cone photoreceptors with adaptive optics
      spectral-domain optical coherence tomography.
AB  - We report the first observations of the three-dimensional morphology of cone
      photoreceptors in the living human retina. Images were acquired with a high-speed
      adaptive optics (AO) spectral-domain optical coherence tomography (SD-OCT)
      camera. The AO system consisted of a Shack-Hartmann wavefront sensor and bimorph
      mirror (AOptix) that measured and corrected the ocular and system aberrations at
      a closed-loop rate of 12 Hz. The bimorph mirror was positioned between the XY
      mechanical scanners and the subject's eye. The SD-OCT system consisted of a
      superluminescent diode and a 512 pixel line scan charge-coupled device (CCD) that
      acquired 75,000 A-scans/s. This rate is more than two times faster than that
      previously reported. Retinal motion artifacts were minimized by quickly acquiring
      small volume images of the retina with and without AO compensation. Camera
      sensitivity was sufficient to detect reflections from all major retinal layers.
      The regular distribution of bright spots observed within C-scans at the inner
      segment / outer segment (IS/OS) junctions and at the posterior tips of the OS
      were found to be highly correlated with one another and with the expected cone
      spacing. No correlation was found between the posterior tips of the OS and the
      other retinal layers examined, including the retinal pigment epithelium.

PMID- 19096731
TI  - Image Reconstruction for a Partially Collimated Whole Body PET Scanner.
AB  - Partially collimated PET systems have less collimation than conventional 2-D
      systems and have been shown to offer count rate improvements over 2-D and 3-D
      systems. Despite this potential, previous efforts have not established image
      based improvements with partial collimation and have not customized the
      reconstruction method for partially collimated data. This work presents an image
      reconstruction method tailored for partially collimated data. Simulated and
      measured sensitivity patterns are presented and provide a basis for modification
      of a fully 3-D reconstruction technique. The proposed method uses a measured
      normalization correction term to account for the unique sensitivity to true
      events. This work also proposes a modified scatter correction based on simulated
      data. Measured image quality data supports the use of the normalization
      correction term for true events, and suggests that the modified scatter
      correction is unnecessary.

PMID- 19096732
TI  - The speed of ecological speciation.
AB  - Adaptation can occur on ecological time-scales (contemporary evolution) and
      adaptive divergence can cause reproductive isolation (ecological speciation).
      From the intersection of these two premises follows the prediction that
      reproductive isolation can evolve on ecological time-scales. We explore this
      possibility in theory and in nature. Finding few relevant studies, we examine
      each in some detail. THEORY: Several models have demonstrated that ecological
      differences can drive the evolution of partial reproductive barriers in dozens to
      hundreds of generations. Barriers likely to evolve quickly include dispersal
      rate, habitat preference and selection against migrants/hybrids. PLANTS: Adjacent
      populations adapting to different fertilizer treatments or to mine tailings can
      develop reproductive barriers within at least 100 generations. These barriers
      include differences in flowering time and selection against migrants/hybrids.
      INVERTEBRATES: Populations on native and introduced host plants can manifest
      reproductive barriers in dozens to hundreds of generations. These barriers
      include local host preference and selection against migrants/hybrids.
      VERTEBRATES: Salmon adapting to divergent breeding environments can show
      restricted gene flow within at least 14 generations. Birds evolving different
      migratory routes can mate assortatively within at least 10-20 generations. Hybrid
      sculpins can become isolated from their ancestral species within at least 20-200
      generations. Ecological speciation can commence within dozens of generations. How
      far it goes is an important question for future research.

PMID- 19096733
TI  - Torso side airbag out-of-position evaluation using stationary and dynamic
      occupants.
AB  - The risk of injury from torso side airbags in out-of-position (OOP) scenarios is
      assessed using stationary occupant conditions. Although stationary tests have
      been effective in frontal airbag assessments, their applicability to torso side
      airbags remains uncertain. Using the MADAYMO facet occupant model, thoracic OOP
      injury was evaluated using full-chest compression criteria (%C) and viscous
      criteria (VC) under stationary occupant conditions and occupant impact velocities
      of 6.0 m/s, 7.0 m/s, 8.0 m/s, and 9.0 m/s. During airbag deployment with a
      stationary occupant, peak %C = 21.8 % while peak VC = 0.86. At 6.0 m/s impact
      velocity, peak %C increased to 35.1 %; at 9.0 m/s impact velocity %C = 45.0 %.
      Similarly, peak VC increased from 1.19 at 6.0 m/s and to 1.96 at 9.0 m/s. These
      results demonstrated that thoracic injury metrics %C and VC increased in dynamic
      testing conditions. Therefore dynamic occupant tests may be required to
      effectively assess OOP thoracic injury risk.

PMID- 19096734
TI  - HAART and Liver: a discussion of hepatic disease in those living with HIV.
      Interview by Paul C Adams.

PMID- 19096735
TI  - The inpatient colonoscopy: a worthwhile endeavour.

PMID- 19096736
TI  - Natural orifice transluminal endoscopic surgery and transrectal abscess drainage:
      is this what we are getting into?

PMID- 19096737
TI  - Endoscopic transcolonic catheter-free pelvic abscess drainage.
AB  - Natural orifice transluminal endoscopic surgery is a novel therapeutic method in
      development that uses different routes of surgical approach. The use of various
      methods, instruments and accessories during this procedure are currently being
      investigated. A case of appendicitis-related intra-abdominal abscess that was
      resolved by a transcolonic endoscopic approach using a wide-channel colonoscope
      with the help of precut and standard sphincterotome without radiological
      percutaneous drainage is presented.

PMID- 19096738
TI  - Local infection after placement of percutaneous endoscopic gastrostomy tubes: a
      prospective study evaluating risk factors.
AB  - BACKGROUND: Due to its high efficacy and technical simplicity, percutaneous
      endoscopic gastrostomy (PEG) has gained wide-spread use. Local infection,
      occurring in approximately 2% to 39% of procedures, is the most common
      complication in the short term. Risk factors for local infection are largely
      unknown and therefore--apart from calculated antibiotic prophylaxis--preventive
      strategies have yet to be determined. OBJECTIVE: To assess the potential patient-
      and procedure-related risk factors for peristomal infection following PEG tube
      placement. METHODS: Potential patient-related (eg, age, sex, diseases, body mass
      index, concomitant antibiotic therapy) and procedure-related (endoscopist
      experience, institutional factors, findings on endoscopy) risk factors and their
      coincidence with local infection, defined as a positive peristomal infection
      three days after PEG tube placement, were evaluated at two institutions. A
      standardized antibiotic prophylaxis was not performed. The peristomal infection
      score was also evaluated in 390 patients. RESULTS: Using a multivariate binary
      regression analysis, four risk factors were established as relevant for local
      infection after PEG: clinical institution (OR 6.69; P = 0.0001), size of PEG
      tubes (15 Fr versus 9 Fr; OR 2.12; P = 0.05), experience of the endoscopist (more
      than 100 investigations versus less than 100 investigations; OR 0.54; P = 0.05)
      and the existence of a malignant underlying disease (OR 2.28; P = 0.019).
      CONCLUSIONS: Similar to other endoscopic interventions, local infection as a
      complication of PEG tube placement depends on the experience of the endoscopist.
      Institutional factors also play a significant role. Additional risk factors
      include PEG tube size and underlying diseases. These findings indicate that the
      local infection after PEG tube placement may be influenced by both endoscopy
      associated factors and by the underlying disease status of the patient.

PMID- 19096739
TI  - Percutaneous endoscopic gastrostomy in children.
AB  - Percutaneous endoscopic gastrostomy has been a valuable tool in nutritional
      rehabilitation since its inception in 1980. Although it was originally described
      in children, a large sector of the adult population is dependent on it for
      nutritional support. Percutaneous endoscopic gastrostomy tube insertion is
      generally a safe procedure. Nevertheless, variable incidence rates of
      complications have been reported. The present review highlights the up-to-date
      indications, contraindications and complications of percutaneous endoscopic
      gastrostomy in children, along with a discussion of issues that need further
      exploring through future research.

PMID- 19096741
TI  - Psychological distress in first year university students: socioeconomic and
      academic stressors, mastery and social support in young men and women.
AB  - PURPOSE: Little is known about the role of stressors associated with university
      life on psychological distress (PD). The aims of this article are to: (1) assess
      the prevalence of PD among students during their first year of university; (2)
      study its associations with stressors (socioeconomic and university-related) and
      protective factors (mastery, social support); and (3) to compare these factors
      according to gender. METHODS: Cross-sectional study of a random sample of
      students aged 18-24 years, in their first year of university in 2005-2006,
      enrolled in the 6 universities of southeastern France. Standardised
      questionnaire, by self-administration or telephone interview. Overall, 1,743
      students agreed to participate (71.0%). RESULTS: PD prevalence was estimated at
      15.7% (95% CI: 12.9-18.5) among the young men and 33.0% (95% CI: 30.2-35.9) among
      the young women. Multiple logistic regressions adjusted for social and
      demographic variables, mode of questionnaire administration, psychiatric history,
      and recent adverse life events, showed that among men PD was associated with lack
      of adjustment to the university academic environment (OR = 1.08; 95% CI: 1.00
      1.17, P = 0.04), and mastery (OR = 0.73; 95% CI: 0.68-0.79). Among women, the
      prevalence of PD was associated with medical studies (OR = 2.46; 95% CI: 1.50
      4.05), lack of adjustment to the university academic environment (OR = 1.07; 95%
      CI: 1.03-1.12), mastery (OR = 0.78; 95% CI: 0.75-0.82), and social support (OR =
      0.68; 95% CI: 0.54-0.85), with a strong negative statistical interaction between
      mastery and lack of adjustment. CONCLUSIONS: This study shows an intermediate
      prevalence of PD among French first-year university students compared with those
      observed in university students in other countries. It suggests that PD is
      related to university-related stressors but failed to find a relation to
      socioeconomic factors. Risk and protective factors for PD in first-year
      university students differed somewhat according to gender. However, mastery
      appeared to have a protective role in both genders. Further research is necessary
      to confirm these results in other universities and years.

PMID- 19096742
TI  - Mental health literacy of autism spectrum disorders in the Japanese general
      population.
AB  - OBJECTIVE: We aimed to clarify the public's mental health literacy of autism
      spectrum disorders (ASD). METHODS: Using a vignette of a young child, 500
      Japanese participants were asked their perspectives, such as causes and
      appropriate coping strategies. For each response from those respondents who
      correctly identified the child as having autism, we tested the effects of sex and
      generation. RESULTS: Two hundred twenty-nine respondents (45.8%) correctly
      identified the child as having autism. Significantly (P < 0.05) more females
      planned practical coping strategies such as contacting public agencies, whereas
      males had relatively more irrelevant perceptions, for example, significantly more
      males attributed ASD to social environment. Significantly more young respondents
      expected psychiatric treatments such as antipsychotic administration to be
      effective, and more seniors estimated low that the prevalence is approximately
      0.01% or less. CONCLUSIONS: The mental health literacy of ASD among the Japanese
      public appears to be acceptable but there is still much room for improvement.
      Females showed more accurate knowledge, possibly reflecting gender roles. Some
      young people are not likely to know of the impact of psychiatric treatment, and
      seniors appear to be unaware of the current broadened recognition of ASD.
      Continued efforts to disseminate accurate information are required, particularly
      among males.

PMID- 19096743
TI  - Bed utilization in two differently organized community mental health services in
      Northern Norway: the VELO-project.
AB  - BACKGROUND: The literature on the dynamics between community- and hospital
      services concerning utilization of psychiatric beds is inconclusive. The
      Norwegian VELO-project provides an opportunity to study this in a natural
      experiment. Two service-systems are compared. The "central-bed system" have
      mainly outpatient- and day-hospital services locally, with psychiatric beds at a
      central mental hospital. The "local-bed system" have only one outpatient clinic,
      with beds at three local inpatient units. Also utilization of sheltered homes was
      studied. Hypotheses were predicted from Goldberg and Huxley's' stage theory and
      the Thornicroft and Tansella's' hydraulic model. MATERIALS AND METHODS: The case
      registries of 2005 were linked across service levels by patients' 11-digit Social
      Security Number. From 1,865 single treatment episodes, 1,348 continuous courses
      by 1,253 individual patients were extracted. RESULTS: For overall utilization of
      psychiatric beds there was only a small difference, were the central-bed system
      utilized 10% less than the other. For utilization of emergency inpatient
      admissions and acute hospital beds, the rate was more than twice in the central
      bed system compared to the other. For utilization of municipalities sheltered
      homes, the rate was three times higher in the local-bed system. DISCUSSION: There
      may be bedrock of need for psychiatric beds regardless of system-organization.
      Distance may in general be a minor issue for utilization of psychiatric beds, and
      may primarily interact with patient- or contextual characteristics associated
      with acute situations. Activity of day-hospital services rather than outpatient
      consultations may affect utilization of sheltered homes. The main theoretical
      models are conceptually useful, although more research is needed to specify
      mechanisms.

PMID- 19096744
TI  - Factors predicting osteoporosis treatment initiation in a regionally based
      cohort.
AB  - Osteoporosis treatment initiation was assessed during the year after baseline BMD
      testing in 8,689 previously untreated women. Treatment initiation increased
      progressively as BMD T-scores decreased, but there was a gradient response rather
      than step increases at conventional T-score intervention thresholds.
      INTRODUCTION: Bone mineral density (BMD) testing is used to identify those at
      high fracture risk and guide osteoporosis treatment (OTx) initiation. Clinical
      guidelines have used the World Health Organization T-score diagnostic cutoffs as
      thresholds for treatment intervention. Our objective was to assess whether OTx
      initiation tracks these T-score cutoffs. METHODS: Eight thousand six hundred and
      eighty-nine women age > or = 50 years who had not been dispensed any OTx
      medication in the year prior to baseline BMD were identified from a regionally
      based database in the Province of Manitoba, Canada, and OTx initiation rates were
      analyzed. RESULTS: Forty-four percent of women were dispensed OTx in the year
      after BMD. OTx initiation increased progressively as BMD T-scores decreased (8.2%
      normal, 41.0% osteopenic, 78.5% osteoporotic, p-for-trend < 0.0001). There was a
      gradient response to OTx initiation, rather than step increases at conventional T
      score intervention thresholds. BMD was strongly associated with OTx (p < 0.0001)
      while age, weight, and fracture in the last year were not. CONCLUSIONS:
      Physicians rely heavily on BMD T-score to decide on OTx initiation. Although
      guidelines suggest using clinical risk factors to guide decision making, we did
      not see evidence of this. More explicit methods of reporting fracture risk may
      help physicians select patients who are likely to derive the largest benefit from
      OTx.

PMID- 19096745
TI  - Strontium ranelate improves bone strength in ovariectomized rat by positively
      influencing bone resistance determinants.
AB  - SUMMARY: Treatment of adult ovariectomized (OVX) rats with strontium ranelate
      prevented vertebral biomechanics degradation as a result of the prevention of
      bone loss and micro-architecture deterioration associated to an effect on
      intrinsic bone material quality. Strontium ranelate influenced the determinants
      of bone strength by prevention of ovariectomy-induced changes which contribute to
      explain strontium ranelate antifracture efficacy. INTRODUCTION: Strontium
      ranelate effects on the determinants of bone strength in OVX rats were evaluated.
      METHODS: Adult female Sprague-Dawley rats were OVX, then treated daily for 52
      weeks with 125, 250, or 625 mg strontium ranelate/kg. Bone strength, mass, micro
      architecture, turnover, and intrinsic quality were assessed. RESULTS: Strontium
      ranelate prevented ovariectomy-induced deterioration in mechanical properties
      with energy necessary for fracture completely maintained vs. SHAM at 625
      mg/kg/day, which corresponds to the clinical dose. This was related to a dose
      dependent effect on bone volume, higher trabeculae number, and lower trabecular
      separation in strontium ranelate vs. OVX. Load and energy required to induce
      lamella deformation were higher with strontium ranelate than in OVX and in SHAM,
      indicating that the bone formed with strontium ranelate is able to withstand
      greater damage before fracture. Bone formation was maintained high or even
      increased in strontium ranelate as shown by mineralizing surfaces and alkaline
      phosphatase while strontium ranelate led to reductions in deoxypyridinoline.
      CONCLUSION: Strontium ranelate administered at 625 mg/kg/day for 52 weeks
      prevented OVX-induced biomechanical properties deterioration by influencing the
      determinants of bone strength: it prevented bone loss and micro-architecture
      degradation in association with an effect on intrinsic bone quality. These
      beneficial effects on bone contribute to explain strontium ranelate antifracture
      efficacy.

PMID- 19096747
TI  - Tibial or hip BMD predict clinical fracture risk equally well: results from a
      prospective study in 700 elderly Swiss women.
AB  - SUMMARY: In a randomly selected cohort of Swiss community-dwelling elderly women
      prospectively followed up for 2.8 +/- 0.6 years, clinical fractures were assessed
      twice yearly. Bone mineral density (BMD) measured at tibial diaphysis (T-DIA) and
      tibial epiphysis (T-EPI) using dual-energy X-ray absorptiometry (DXA) was shown
      to be a valid alternative to lumbar spine or hip BMD in predicting fractures.
      INTRODUCTION: A study was carried out to determine whether BMD measurement at the
      distal tibia sites of T-EPI and T-DIA is predictive of clinical fracture risk.
      METHODS: In a predefined representative cohort of Swiss community-dwelling
      elderly women aged 70-80 years included in the prospective, multi-centre Swiss
      Evaluation of the Methods of Measurement of Osteoporotic Fracture risk (SEMOF)
      study, fracture risk profile was assessed and BMD measured at the lumbar spine
      (LS), hip (HIP) and tibia (T-DIA and T-EPI) using DXA. Thereafter, clinical
      fractures were reported in a bi-yearly questionnaire. RESULTS: During 1,786 women
      years of follow-up, 68 clinical fragility fractures occurred in 61 women. Older
      age and previous fracture were identified as risk factors for the present
      fractures. A decrease of 1 standard deviation in BMD values yielded a 1.5-fold
      (HIP) to 1.8-fold (T-EPI) significant increase in clinical fragility fracture
      hazard ratio (adjusted for age and previous fracture). All measured sites had
      comparable performance for fracture prediction (area under the curve range from
      0.63 [LS] to 0.68 [T-EPI]). CONCLUSION: Fracture risk prediction with BMD
      measurements at T-DIA and T-EPI is a valid alternative to BMD measurements at LS
      or HIP for patients in whom these sites cannot be accessed for clinical,
      technical or practical reasons.

PMID- 19096746
TI  - To stop or not to stop, that is the question.
AB  - Treatment aimed at preventing fractures should be stopped if evidence of
      continued antifracture efficacy is lacking, if continued treatment increases bone
      fragility by adversely affecting matrix properties, and if stopping does not
      increased bone fragility. Credible evidence of antifracture efficacy beyond 5
      years is lacking because of attrition of the cohort originally allocated to
      treatment or placebo and lack of controls. Prolonged suppression of remodeling is
      associated with accumulation of microdamage, advanced glycation products and
      increased tissue mineral density in animal studies but the structural benefits
      appear to out weight these adverse effects. Atypical minimal trauma
      subtrochanteric fractures are associated with prolonged treatment in human
      subjects but these are exceedingly rare. Stopping treatment does result in the
      reemergence of remodeling, rapidly with some drugs, more slowly with others while
      fracture rates are increased in poor compliers to treatment. Thus, within the
      constraints of limited evidence, I infer that stopping therapy is more likely to
      do net harm than continuing therapy - treatment should be continued in the
      majority of individuals.

PMID- 19096748
TI  - Underweight and obese states both associate with worse disease activity and
      physical function in patients with established rheumatoid arthritis.
AB  - Obesity is characterised by low-grade inflammation and could potentially affect
      disease activity and severity in patients with rheumatoid arthritis (RA). Body
      mass index (BMI), body fat (BF), erythrocyte sedimentation rate, C-reactive
      protein, disease activity score 28, physical function (health assessment
      questionnaire) and presence of erosions and joint surgery were assessed in 294
      (female=219) volunteers with established RA [age 63.3 (56.2-69.6); disease
      duration 13 (7-20) years]. Smoking status, rheumatoid factor and anti-cyclic
      citrullinated peptide positivity were also assessed. BMI and BF independently
      associated with disease characteristics. Compared to normal-weight patients,
      underweight and obese had higher C-reactive protein (p=0.046) and physical
      dysfunction (p=0.034). BMI or BF did not associate with presence of erosions or
      joint surgery. In patients with established RA, both very low and very high BMI
      and BF associate independently with increased disease activity and physical
      dysfunction; however, this does not seem to associate with presence of erosions
      or joint surgery. Further longitudinal studies are required to address this
      apparent dissociation.

PMID- 19096749
TI  - Evaluation of small bowel tumors: MR enteroclysis.
AB  - Magnetic resonance imaging (MRI) of the small bowel has become widely accepted at
      centers dedicated to the diagnosis and treatment of inflammatory bowel disease,
      due to the method's diagnostic efficacy. MR enteroclysis is an imaging modality
      that combines the advantages of enteroclysis and multiplanar MR and allows the
      detection and the manifestations of small bowel diseases wherever they are
      located (intraluminal, intramural, or extramural). Magnetic resonance
      enteroclysis (MRE) is an emerging technique used for the detection and evaluation
      of small bowel neoplasms. This article illustrates the imaging appearances of
      small bowel tumors on MRI and the usefulness of MR enteroclysis in the diagnosis
      and categorization of these tumors, also discussing the role of MRE in comparison
      with other diagnostic modalities.

PMID- 19096750
TI  - Prevalence and severity of atherosclerosis in renal artery in Northwest Indian
      population: an autopsy study.
AB  - BACKGROUND: Atherosclerosis has been described as the most common cause of renal
      artery stenosis. The purpose of this autopsy study was to assess the
      preponderance and severity of atherosclerotic changes in renal artery in
      different age groups in normal population. METHODS: Ninety renal arteries from 45
      cadavers above 30 years of age were obtained at autopsy. Fifty-four renal
      arteries were studied grossly after Sudan IV staining for extent and severity of
      fatty deposits in terms of Atherosclerotic index (AI). Another 36 renal arteries
      were studied microscopically for changes in different layers and at different
      sites of artery and luminal narrowing, if any with advancing age. RESULTS: In
      grossly stained specimens, incidence and AI which is the marker of extent and
      severity of lesions were found to increase gradually with advancement of age.
      Increased incidence of atherosclerotic changes with better nutritional status was
      recorded. In microscopically studied specimens, intimal thickness which is a
      marker of disease also showed upward rise with advancing age. Renal artery
      stenosis was prevalent in 13.8% cases. Lesions were most commonly detected at
      renal ostium and proximal segment. CONCLUSIONS: Fatty changes appear with
      advancing age. Advanced types of changes including fibrous plaques, calcification
      and ulceration were noticed first in fifth decade. The changes were usually
      bilateral. Proximal segment was the most affected part. Four cases had less than
      50% and one case had 70% luminal narrowing. The changes were only moderately
      severe in most of the cases.

PMID- 19096751
TI  - Anatomical basis of transgluteal pudendal nerve block.
AB  - BACKGROUND: The pudendal nerve may become entrapped either within the pudendal
      canal or near the sacrotuberous ligament resulting in a partial conduction block.
      The goal of the present anatomical study was to assess a new transgluteal
      injection technique in terms of the precise injection site and the resulting
      distribution of the injected agent. MATERIALS AND METHODS: This study was carried
      out using eight fresh human cadavers. An epidural needle with a removable wing
      was inserted and the catheter position visualized using MRI. Through the catheter
      10 ml of gadolinium contrast medium was injected into three of the cadavers. A
      further four cadavers were injected with latex and blue pigment and the pelvi
      perineal area of each then separated from the trunk for freezing before being cut
      into 4-8 mm thick sections with an electric bandsaw. One final cadaver was
      injected with a mix of gadolinium (5 ml) and latex (5 ml) and both the MRI and
      anatomical procedures outlined above were performed. RESULTS: Using MRI, we
      clearly imaged both the site of injection, near the trunk of the pudendal nerve,
      and the gadolinium contrast medium in different pelvic and perineal areas and
      around the fascia of the obturator internus and levator ani muscle. Concerning
      the anatomical study, latex was observed mainly around the sacrotuberous
      ligament, along the obturator internus muscle and in the perineal area in contact
      with the dividing branches of the pudendal nerve. The mixed injection of latex
      and gadolinium in the pudendal canal was found with the same localization between
      MRI and anatomical studies. CONCLUSION: This easily performed technique should
      provide a new approach for treating perineal neuralgia via pudendal nerve block
      in the consultation room without the need for computed tomography.

PMID- 19096752
TI  - Clinical and pathological features of primary carcinoma of the cystic duct.
AB  - BACKGROUND: According to Farrar's criteria, a tumor restricted to the cystic duct
      is defined as cystic duct carcinoma, but this definition excludes advanced
      carcinoma originating from the cystic duct. PATIENTS AND METHODS: For the purpose
      of this study, primary cystic duct carcinoma was defined as a tumor originating
      from the cystic duct. We investigated the clinicopathological features of 15
      cystic duct carcinomas, including 13 that did not fit Farrar's criteria, and
      compared them with those of 52 cases of gallbladder carcinoma and 161 cases of
      extrahepatic bile duct carcinoma. RESULTS: The incidence of primary cystic duct
      carcinoma was 6.6% among all malignant biliary tumors. The main symptom was
      jaundice in 67% of cases. The operative procedures employed ranged from
      cholecystectomy to hepatopancreatoduodenectomy. The cases of cystic duct
      carcinoma and bile duct carcinoma showed a high frequency of perineural
      infiltration. The overall 5-year survival rate of the 15 patients was 40%.
      CONCLUSION: Patients with advanced cystic duct carcinoma show a high frequency of
      jaundice and perineural infiltration. Our data suggest that cystic duct carcinoma
      may be considered a distinct subgroup of gallbladder carcinoma. Radical surgery
      is necessary for potentially curative resection in patients with advanced cystic
      duct carcinoma.

PMID- 19096753
TI  - Splenic-intrahepatic left portal shunt in an adult patient with extrahepatic
      portal vein obstruction without recurrence after pancreaticoduodenectomy.
AB  - In the last decade, a superior mesenteric-intrahepatic left portal shunt (Rex
      shunt) has been reported for successful management of extrahepatic portal vein
      obstruction in children. However, in adults, a mesocaval shunt has been generally
      performed for the surgical management of extrahepatic portal vein obstruction
      because of the complexity of the underlying disease and the difficulty of the
      superior mesenteric-intrahepatic left portal shunt. We herein report an adult
      patient who was successfully treated by splenic-intrahepatic left portal shunt
      with an artificial graft (6-mm polytetrafluoroethylene) for complete obstruction
      of the extrahepatic portal vein following pancreaticoduodenectomy. The shunt
      procedure not only relieved portal hypertension but also restored hepatic portal
      flow. In the near future, the Rex shunt should be considered for a beneficial
      management of extrahepatic portal vein obstruction, even in adults.

PMID- 19096754
TI  - Mucin-producing carcinoma of the gallbladder associated with primary sclerosing
      cholangitis and ulcerative colitis.
AB  - Mucin-producing carcinoma of the gallbladder is very rare. We report here a case
      of mucin-producing carcinoma of the gallbladder associated with primary
      sclerosing cholangitis (PSC) and ulcerative colitis (UC). A 74-year-old female
      had been treated with salazosulfapyridine and ursodesoxycholic acid becase of UC
      and PSC. After 7 years of treatment, laboratory data showed that the liver
      function took a turn for the worse, and the patient was admitted to our hospital
      for further examination. Enhanced computed tomography and ultrasonography showed
      an enlarged gallbladder associated with wall thickening and diffuse papillary
      protrusion. Endoscopic retrograde cholangiography showed stenosis and dilatation
      of the bile duct, which were compatible with PSC. Under the diagnosis of an early
      carcinoma of the gallbladder, we performed simple cholecystectomy. The tumor
      showed a papillary growth pattern located diffusely in the gallbladder with a
      massive amount of mucin filling the gallbladder. Histologically, it was diagnosed
      as a papillary adenocarcinoma localized in the mucosal layer. To the best of our
      knowledge, this is the first case of mucin-producing carcinoma of the gallbladder
      associated with PSC and UC. PSC and UC patients should be regarded as a high-risk
      group not only for cholangiocarcinoma but also carcinoma of the gallbladder.

PMID- 19096755
TI  - Successful treatment of myeloid neoplasms associated with PDGFRA rearrangement
      with imatinib mesylate.
AB  - Hypereosinophilic syndromes (HES) constitute a rare and heterogeneous group of
      disorders, defined as persistent and marked blood eosinophilia associated with
      evidence of eosinophil-induced organ damage. Cardiac dysfunction is the most
      frequent result of end-organ damage and is the major cause of morbidity and
      mortality among patients with HES. Despite patients with FIP1-like-1-platelet
      derived growth factor alpha (FIP1L1-PDGFRA) associated HES (myeloid neoplasms
      associated with PDGFRA rearrangement) have been shown to respond to low-dose
      imatinib with a complete and durable hematological and cytogenetic remission,
      influences of imatinib on clinical manifestations related to hypereosinophilia
      heart involvement are variable. Here we describe the case of a young male patient
      with severe heart involvement who had a prompt, clinical and hematological
      complete remission following administration of imatinib. However, as
      endomyocardial fibrosis and related loss of function are deteriorated after
      initiation of imatinib therapy, valvular replacement and tricuspid annuloplasty
      had to perform to restore his heart function. Our finding concurs with recent
      reports that severe heart involvement was irreversible with imatinib treatment.

PMID- 19096756
TI  - Convexity dural cavernous malformation with intradural and extradural extension
      mimicking a meningioma: a case report.
AB  - BACKGROUND: Dural-based cavernous malformations are rare and have been more
      commonly described in the middle fossa. Fewer than 20 cases outside of the middle
      fossa have been reported and they often mimic more commonly found lesions such as
      meningiomas or hemangiopericytomas. CASE DESCRIPTION: We describe the unusual
      case of a right frontal convexity dural cavernous malformation with intradural
      and extradural components as well as erosion through the calvarium. The patient
      underwent a right frontal craniotomy and en-bloc resection of the mass. Final
      pathologic interpretation confirmed a cavernous malformation that had eroded
      through the calvarium. CONCLUSION: Dural-based cavernous malformations are a rare
      entity, but should be considered in the differential diagnosis of atypical
      appearing dural-based lesions and soft subgaleal masses. If atypical features are
      present, further radiographic investigations should be undertaken. To our
      knowledge, this is the only reported case of a dural-based cavernous malformation
      eroding through the calvarium and presenting initially as a soft scalp mass.

PMID- 19096758
TI  - Hemicrania continua unresponsive or partially responsive to indomethacin: does it
      exist? A diagnostic and therapeutic dilemma.
AB  - Hemicrania continua (HC) is a primary headache disorder characterized by a
      continuous, unilateral headache that varies in intensity, waxing and waning
      without disappearing completely. Ipsilateral cranial autonomic features and
      response to indomethacin are essential features for the diagnosis of HC. We
      hereby, describe three patients with the clinical phenotypes of HC in whom
      response to indomethacin was either incomplete or not sustained. We also review
      the literature especially for the presence of indomethacin response and
      ipsilateral cranial autonomic features.

PMID- 19096757
TI  - Comparison of the effect of decompressive craniectomy on different neurosurgical
      diseases.
AB  - BACKGROUND: Many previous studies have reported that decompressive craniectomy
      has improved clinical outcomes in patients with intractable increased
      intracranial pressure (ICP) caused by various neurosurgical diseases. However
      there is no report that compares the effectiveness of the procedure in the
      different conditions. The authors performed decompressive craniectomy following a
      constant surgical indication and compared the clinical outcomes in different
      neurosurgical diseases. MATERIALS AND METHODS: Seventy five patients who
      underwent decompressive craniectomy were analysed retrospectively. There were 28
      with severe traumatic brain injury (TBI), 24 cases with massive intracerebral
      haemorrhage (ICH), and 23 cases with major infarction (MI). The surgical
      indications were GCS score less than 8 and/or a midline shift more than 6 mm on
      CT. The clinical outcomes were assessed on the basis of mortality and Glasgow
      Outcome Scale (GOS) scores. The changes of ventricular pressure related to the
      surgical intervention were also compared between the different disease groups.
      FINDINGS: Clinical outcomes were evaluated 6 months after decompressive
      craniectomy. The mortality was 21.4% in patients with TBI, 25% in those with ICH
      and 60.9% in MI. A favourable outcome, i.e. GOS 4-5 (moderate disability or
      better) was observed in 16 (57.1%) patients with TBI, 12 (50%) with ICH and 7
      (30.4%) with MI. The change of ventricular pressure after craniectomy and was
      53.2 (reductions of 17.4%) and further reduced by 14.9% (with dural opening) and
      (24.8%) after returning to its recovery room, regardless of the diseases group.
      CONCLUSIONS: According to the mortality and GOS scores, decompressive craniectomy
      with dural expansion was found to be more effective in patients with ICH or TBI
      than in the MI group. However, the ventricular pressure change during the
      decompressive craniectomy was similar in the different disease groups. The
      authors thought that decompressive craniectomy should be performed earlier for
      the major infarction patients.

PMID- 19096759
TI  - Iron- and 2-oxoglutarate-dependent dioxygenases: an emerging group of molecular
      targets for nickel toxicity and carcinogenicity.
AB  - Nickel compounds are important occupational and environmental pollutants. Chronic
      exposure to these pollutants has been connected with increased risks of
      respiratory cancers and cardiovascular diseases. However, it is still not clear
      what are the specific molecular targets for nickel toxicity and carcinogenicity.
      Here, we propose that the iron- and 2-oxoglutarate-dependent dioxygenase family
      enzymes are important intracellular targets that mediate the toxicity and
      carcinogenicity of nickel. In support of this hypothesis, our data show that
      three different classes of enzymes in this iron- and 2-oxoglutarate-dependent
      dioxygenase family, including HIF-prolyl hydroxylase PHD2, histone demethylase
      JHDM2A/JMJD1A, and DNA repair enzyme ABH3, are all highly sensitive to nickel
      inhibition. Inactivation of these enzymes accounts for a number of deleterious
      effects caused by nickel in cells, namely hypoxia-mimic stress and aberrant
      epigenetic changes. Future studies on nickel's effects on these iron- and 2
      oxoglutarate-dependent dioxygenases would deepen our understanding on nickel
      toxicity and carcinogenicity.

PMID- 19096760
TI  - Ectopic expression of VlmybA1 in grapevine activates a narrow set of genes
      involved in anthocyanin synthesis and transport.
AB  - The colour of the red wine is essentially due to the release of anthocyanins from
      the red skin of grape berries during the process of wine making. Anthocyanins are
      synthesized during ripening of the berries under the control of VvMYBA1
      transcription factor that controls the expression of UFGT. In order to identify
      the whole set of downstream regulated genes, we targeted constitutive ectopic
      expression of VlmybA1-2 into grapevine hairy roots and plants. The ectopic
      expression of VlmybA1-2 triggered de novo production and storage of anthocyanins
      in all transgenic vegetative organs, leading to a very intense red coloration,
      and did not interfere with proanthocyanidin (PA) biosynthesis. The ectopic red
      pigmentation was due to the accumulation of anthocyanins in vacuoles and
      anthocyanin vacuolar inclusion (AVIs) in all organs but only in specific tissues.
      A transcriptomic analysis using a 14 K oligoarray revealed that the ectopic
      expression of VlmybA1-2 activated only few genes, most of which are involved in
      both PA and anthocyanin biosynthesis, while the expression of BAN and LAR (two
      specific genes of the PA biosynthesis pathway) was unaffected. Among these, 4
      genes emerged given the amplitude of their up-regulation, quantitatively similar
      to VlmybA1-2 itself. In addition to the previously described UFGT, this set
      comprised an isogen of GST, an O-methyltransferase, both of which are supposed to
      play a role in the anthocyanin biosynthesis pathway, as well as a candidate gene
      putatively involved in the vacuolar anthocyanin transport in grapevine
      (anthoMATE). Together, these results suggest that MybA1 activates the last steps
      of anthocyanin synthesis and transport through the regulation of a narrow,
      specific spectrum of genes regulated as a cluster.

PMID- 19096761
TI  - NF-kappaB suppression provokes the sensitization of hormone-resistant breast
      cancer cells to estrogen apoptosis.
AB  - The progression of breast cancer cells to estrogen-independent growth may be
      accompanied with the paradoxical cell sensitization to estrogen apoptotic action;
      however, the mechanism of this phenomenon is still unclear. In the present study,
      we have shown that the sensitization of hormone-resistant breast cancer cells to
      estrogen apoptotic action is accompanied with the gradual NF-kappaB suppression.
      Using the chemical inhibitors of NF-kappaB as well as the dominant-negative NF
      kappaB constructs, we have proved the sufficiency of NF-kappaB inhibition for the
      sensitization of the resistant cells to estrogen apoptosis. Estradiol treatment
      results in the additional suppression of NF-kappaB, demonstrating the possible NF
      kappaB involvement in the regulation of cell response to estrogens. Totally, the
      results presented suggest that the constitutive NF-kappaB suppression in the
      estrogen-independent cells may be considered as one of the factors resulting in a
      imbalance between pro- and anti-apoptotic pathways and enhancement in estrogen
      apoptotic action in the cells.

PMID- 19096762
TI  - Progesterone, but not estradiol, synchronizes circadian oscillator in the uterus
      endometrial stromal cells.
AB  - The circadian oscillator is generated within the suprachiasmatic nuclei and
      synchronizes circadian clocks in numerous peripheral tissues. The molecular basis
      is composed of a number of genes and proteins that form transcriptional and
      translational feedback loops. Such molecular oscillators are also operative in
      peripheral tissues, including in the uterus. Although ovarian steroids regulate
      the function of uterine endometrial stromal cells, the modulation of ovarian
      steroids on the circadian rhythms remains unknown. Here we investigate the
      possibility that estradiol (E2) and progesterone (P4) modulate the circadian
      oscillator of the stromal cells. The study using transgenic rats constructed with
      Period 2 (Per2) promoter-destabilized luciferase (Per2-dLuc) gene, with the real
      time monitoring system of Per2-dLuc oscillation. The stromal cells displayed
      constant Per2-dLuc oscillation after treatment with dexamethasone, suggesting
      that the circadian oscillator is operative. However, the circadian oscillator was
      disrupted by in vivo administration of human chorionic gonadotropin (hCG)
      following equine chorionic gonadotropin (eCG), although it was altered into a
      rhythmic pattern 4 days later following hCG. Chronic treatment with P4 induced
      constant Per2-dLuc oscillation in the stromal cells from eCG-treated immature and
      pregnant rats, whereas E2 did not promote such a rhythmic Per2-dLuc oscillation.
      Collectively, P4 synchronizes the circadian oscillator of the uterus endometrial
      stromal cells through transcriptional and translational feedback loops of the
      clockwork system.

PMID- 19096763
TI  - Toll-like receptors and their role in carcinogenesis and anti-tumor treatment.
AB  - Toll-like receptors (TLRs) have been described as major components of the innate
      immune system, recognizing the conserved molecular structures found in the large
      groups of pathogens called pathogen-associated molecular patterns (PAMPs). TLR
      expression is ubiquitous, from epithelial to immunocompetent cells. TLR ligation
      triggers several adapter proteins and downstream kinases, leading to the
      induction of key pro-inflammatory mediators but also anti-inflammatory and anti
      tumor cytokines. The result of this activation goes beyond innate immunity to
      shape the adaptive responses against pathogens and tumor cells, and maintains
      host homeostasis via cell debris utilization. TLRs have already become potent
      targets in infectious disease treatment and vaccine therapy and in neoplastic
      disease treatment, due to their ability to enhance antigen presentation. However,
      some studies show the dual effect of TLR stimulation on malignant cells: they can
      be proapoptotic or promote survival under different conditions. It is therefore
      crucial to design further studies assessing the biology of these receptors in
      normal and transformed cells. The established role of TLRs in human disease
      therapy is based on TLR7 and TLR4 agonists, respectively for the novel treatment
      of some types of skin cancer and for the anti-hepatitis B virus vaccine. Some
      clinical trials involving TLR agonists as potent enhancers of the anti-tumor
      response in solid tumors have begun.

PMID- 19096764
TI  - Acheron, an novel LA antigen family member, binds to CASK and forms a complex
      with Id transcription factors.
AB  - Acheron, a Lupus antigen ortholog, was identified as a novel death-associated
      transcript from the intersegmental muscles of the moth Manduca sexta. Acheron is
      phylogenetically-conserved and represents a new sub-family of Lupus antigen
      proteins. Acheron is expressed predominantly in neurons and muscle in
      vertebrates, and regulates several developmental events including myogenesis,
      neurogenesis and possibly metastasis. Using Acheron as bait, we performed a yeast
      two-hybrid screen with a mouse embryo cDNA library and identified CASK-C, a novel
      CASK/Lin-2 isoform, as an Acheron binding partner. Acheron and CASK-C bind via
      the C-terminus of Acheron and the CaMKII-like domain of CASK-C. Co
      immunoprecipitation assays verify this interaction and demonstrate that Acheron
      also forms a complex with all members of the Id (inhibitor of differentiation)
      proteins. Taken together, these data suggest a mechanism by which Acheron may
      regulate development and pathology.

PMID- 19096765
TI  - Effects of lead and/or cadmium on the expression of metallothionein in the kidney
      of rats.
AB  - Lead acetate (300 mg/L) and/or cadmium chloride (50 mg/L) were administered as
      drinking water of Sprague-Dawley rats for 8 weeks to investigate the possible
      combined effect of these metals on the expression of metallothionein (MT) in
      kidneys. Immunohistochemical staining and real-time quantitative polymerase chain
      reaction analyses were performed on kidney samples to identify the distribution
      of MT and to quantify the relative expression levels of MT-1 and MT-2 gene,
      respectively. There is no significant difference in distribution of the
      intensity, amount of MT immunostaining, and expression level of MT-1 and MT-2
      gene in the kidneys between the lead group and control group (P > 0.05), whereas
      those in the cadmium group and (Pb + Cd) group were significantly higher than
      that in the control group (P < 0.01). Compared to the (Pb + Cd) group with the
      lead or cadmium group, the expression level of MT-1 and MT-2 gene increased
      significantly (P < 0.01). In summary, there was an obvious synergistic effect of
      lead combined with cadmium on the expression of metallothionein in the kidney of
      rats.

PMID- 19096766
TI  - Should we be cautious on the use of commercially available antibodies to dopamine
      receptors?
AB  - Evidence indicate that it is difficult to obtain specific antibodies to G protein
      coupled receptors and different technical difficulties may allow the generation
      of antibodies that lack specificity. We conducted experiments to validate the
      specificity of commercially available antibodies raised against dopamine (DA)
      receptors hD(1), hD(4), and hD(5) using a transfection approach: we studied
      whether, in HEK 293 cells selectively transfected with the various cloned
      subtypes, each antibody generates bands only in cells expressing its cognate
      receptor but not in those expressing the other DA receptors. Our results
      demonstrated that hD(1) and hD(4) receptor antibodies recognize not only their
      respective epitope, but also other DA receptor subtypes, while for the hD(5)
      receptor detection, we observed a signal only in the lane loaded with hD(5)
      transfected HEK 293 cells, although with a lack of purity. Therefore, we
      recommend caution on the use of commercially available DA receptor antibodies.

PMID- 19096767
TI  - Nanotechnology for regenerative medicine.
AB  - Future biomaterials must simultaneously enhance tissue regeneration while
      minimizing immune responses and inhibiting infection. While the field of tissue
      engineering has promised to develop materials that can promote tissue
      regeneration for the entire body, such promises have not become reality. However,
      tissue engineering has experienced great progress due to the recent emergence of
      nanotechnology. Specifically, it has now been well established that increased
      tissue regeneration can be achieved on almost any surface by employing novel nano
      textured surface features. Numerous studies have reported that nanotechnology
      accelerates various regenerative therapies, such as those for the bone, vascular,
      heart, cartilage, bladder and brain tissue. Various nano-structured polymers and
      metals (alloys) have been investigated for their bio (and cyto) compatibility
      properties. This review paper discusses several of the latest nanotechnology
      findings in regenerative medicine (also now called nanomedicine) as well as their
      relative levels of success.

PMID- 19096768
TI  - Understanding the BIG results: Insights from the BIG 1-98 trial analyses.
AB  - Third-generation aromatase inhibitors (AIs), including letrozole, are now
      standard therapy for initial adjuvant endocrine treatment of postmenopausal women
      with early breast cancer. The International Breast Cancer Study Group's Breast
      International Group (BIG) 1-98 trial is examining efficacy and safety of
      letrozole or tamoxifen, whether used upfront or sequentially, for postmenopausal
      with hormone receptor-positive breast cancer. Women in the BIG 1-98 trial were
      randomized to either 5 years' monotherapy with tamoxifen or letrozole (trial arms
      A and B, respectively), or to 5 years' sequential therapy with 2 years of
      tamoxifen followed by 3 years of letrozole, or 2 years of letrozole followed by 3
      years of tamoxifen (arms C and D, respectively). Results of the primary core
      analysis (PCA) of BIG 1-98, at a median follow-up of 25.8 months, showed a
      significant improvement in disease-free survival for patients treated with
      initial adjuvant letrozole relative to those on tamoxifen (P=0.003). Of interest,
      there was an important reduction in distant metastases, the most common and
      ultimately fatal type of early recurrence, for patients allocated to initial
      letrozole compared with initial tamoxifen. Since the PCA, there have been further
      analyses of BIG 1-98 with variations in the cohorts analyzed and follow-up
      period. The first and largest central pathology review in an adjuvant AI trial to
      date was also performed in the BIG 1-98 trial. In light of the impending sequence
      analysis, expected in late 2008, the goal of this article is to describe and
      summarize the breadth of information learned to date and highlight the key
      findings regarding the efficacy and safety of letrozole in the initial adjuvant
      setting.

PMID- 19096769
TI  - Transmission electron microscopy of VX2 liver tumors after high-intensity focused
      ultrasound ablation enhanced with SonoVue.
AB  - INTRODUCTION: The purpose of this study was to observe sequential changes in
      rabbit VX2 liver tumors using transmission electron microscopy after high
      intensity focused ultrasound (HIFU) ablation enhanced with the contrast agent
      SonoVuer (Bracco, Milan, Italy). METHODS: Thirty New Zealand rabbits with VX2
      liver tumors were randomly divided into two groups. The liver tumors of rabbits
      in Group A underwent single HIFU ablation; those in Group B were given the
      ultrasound contrast agent SonoVue 0.2 mL/kg before HIFU exposure. Five rabbits
      from each of the two groups were killed at 0 hours, 6 days, and 14 days after
      HIFU ablation. Tissue samples that included targeted and untargeted tissue were
      observed using transmission electron microscopy. RESULTS: Using transmission
      electron microscopy, it was evident that most of the cellular organs in the
      targeted areas of tumors in Groups A and B had disappeared early after HIFU, but
      the basic cell structure was seen in Group A. On the sixth day after HIFU
      ablation, all cells in the targeted areas were disrupted, and fibrous bands were
      detected in the rims of targeted areas in both groups. In the surrounding areas,
      cell swelling in Group B was more severe than in Group A, and a greater number of
      apoptotic bodies were found in Group B. CONCLUSION: The use of an ultrasound
      contrast agent can enhance the effects of HIFU ablation on the destruction of
      cell ultrastructure and can enlarge the region of HIFU ablation; this provides
      experimental evidence for the use of contrast agents in controlling the effects
      of HIFU.

PMID- 19096770
TI  - Discovery of the aquaporins and development of the field.
AB  - The study of water transport began long before the molecular identification of
      water channels with studies of water-permeable tissues. The discovery of the
      first aquaporin, AQP1, occurred during experiments focused on the identity of the
      Rh blood group antigens. Since then the field has expanded dramatically to study
      aquaporins in all types of organisms. In mammals, some of the aquaporins
      transport only water. However, there are some family members that collectively
      transport a diverse set of solutes. The aquaporins can be regulated by factors
      that affect channel permeability or subcellular localization. An extensive set of
      studies examines the physiological role of many of the mammalian aquaporins.
      However, much is still to be discovered about the physiological role of this
      membrane protein family.

PMID- 19096771
TI  - The AQP structure and functional implications.
AB  - Progress in the structure determination of AQPs has led to a deep understanding
      of water and solute permeation by these small integral membrane proteins. The
      atomic structures now available have allowed the water permeation and exclusion
      of protons to be monitored by molecular dynamics simulations, and have provided a
      framework for assessing the water and solute permeation in great detail by site
      directed mutations. In spite of this, further structural and molecular dynamics
      analyses are required to elucidate the basis for regulation as well as for gas
      permeation, processes that are still to be deciphered.

PMID- 19096772
TI  - Dynamics and energetics of permeation through aquaporins. What do we learn from
      molecular dynamics simulations?
AB  - Aquaporins (AQPs) are a family of integral membrane proteins, which facilitate
      the rapid and yet highly selective flux of water and other small solutes across
      biological membranes. Molecular dynamics (MD) simulations contributed
      substantially to the understanding of the molecular mechanisms that underlie this
      remarkable efficiency and selectivity of aquaporin channels. This chapter reviews
      the current state of MD simulations of aquaporins and related aquaglyceroporins
      as well as the insights these simulations have provided. The mechanism of water
      permeation through AQPs and methods to determine channel permeabilities from
      simulations are described. Protons are strictly excluded from AQPs by a large
      electrostatic barrier and not by an interruption of the Grotthuss mechanism
      inside the pore. Both the protein's electric field and desolvation effects
      contribute to this barrier. Permeation of apolar gas molecules such as CO(2)
      through AQPs is accompanied by a large energetic barrier and thus can only be
      expected in membranes with a low intrinsic gas permeability. Additionally, the
      insights from simulations into the mechanism of glycerol permeation through the
      glycerol facilitator GlpF from E. coli are summarized. Finally, MD simulations
      are discussed that revealed that the aro-matic/arginine constriction region is
      generally the filter for uncharged solutes, and that AQP selectivity is
      controlled by a hydrophobic effect and steric restraints.

PMID- 19096773
TI  - In vitro analysis and modification of aquaporin pore selectivity.
AB  - Aquaporins enable the passage of a diverse set of solutes besides water. Many
      novel aquaporin permeants, such as antimonite and arsenite, silicon, ammonia, and
      hydrogen peroxide, have been described very recently. By the same token, the
      number of available aquaporin sequences has rapidly increased. Yet, sequence
      analyses and structure models cannot reliably predict permeability properties.
      Even the contribution to pore selectivity of individual residues in the channel
      layout is not fully understood. Here, we describe and discuss established in
      vitro assays for water and solute permeability. Measurements of volume change due
      to flux along osmotic or chemical gradients yield quantitative biophysical data,
      whereas phenotypic growth assays can hint at the relevance of aquaporins in the
      physiological setting of a certain cell. We also summarize data on the
      modification of pore selectivity of the prototypical water-specific mammalian
      aquaporin-1. We show that replacing residues in the pore constriction region
      allows ammonia, urea, glycerol, and even protons to pass the aquaporin pore.

PMID- 19096774
TI  - Aquaporins in the kidney.

PMID- 19096775
TI  - Regulation of aquaporin-2 trafficking.
AB  - Principal cells lining renal collecting ducts control the fine-tuning of body
      water homeostasis by regulating water reabsorption through the water channels
      aquaporin-2 (AQP2), aquaporin-3 (AQP3), and aquaporin-4 (AQP4). While the
      localization of AQP2 is subject to regulation by arginine-vasopressin (AVP), AQP3
      and AQP4 are constitutively expressed in the basolateral plasma membrane. AVP
      adjusts the amount of AQP2 in the plasma membrane by triggering its
      redistribution from intracellular vesicles into the plasma membrane. This permits
      water entry into the cells and water exit through AQP3 and AQP4. The
      translocation of AQP2 is initiated by an increase in cAMP following V2R
      activation through AVP. The AVP-induced rise in cAMP activates protein kinase A
      (PKA), which in turn phosphorylates AQP2, and thereby triggers the redistribution
      of AQP2. Several proteins participating in the control of cAMP-dependent AQP2
      trafficking have been identified; for example, A kinase anchoring proteins
      (AKAPs) tethering PKA to cellular compartments; phosphodiesterases (PDEs)
      regulating the local cAMP level; cytoskeletal components such as F-actin and
      microtubules; small GTPases of the Rho family controlling cytoskeletal dynamics;
      motor proteins transporting AQP2-bearing vesicles to and from the plasma membrane
      for exocytic insertion and endocytic retrieval; SNAREs inducing membrane fusions,
      hsc70, a chaperone, important for endocytic retrieval. In addition, cAMP
      independent mechanisms of translocation mainly involving the F-actin cytoskeleton
      have been uncovered. Defects of AQP2 trafficking cause diseases such as
      nephrogenic diabetes insipidus (NDI), a disorder characterized by a massive loss
      of hypoosmotic urine.This review summarizes recent data elucidating molecular
      mechanisms underlying the trafficking of AQP2. In particular, we focus on
      proteins involved in the regulation of trafficking, and physiological and
      pathophysiological stimuli determining the cellular localization of AQP2. The
      identification of proteins and protein-protein interactions may lead to the
      development of drugs targeting AQP2 trafficking. Such drugs may be suitable for
      the treatment of diseases associated with dysregulation of body water
      homeostasis, including NDI or cardiovascular diseases (e.g., chronic heart
      failure) where the AVP level is elevated, inducing excessive water retention.

PMID- 19096777
TI  - Aquaporins as potential drug targets for Meniere's disease and its related
      diseases.
AB  - The homeostasis of water in the inner ear is essential for maintaining function
      of hearing and equilibrium. Since the discovery of aquaporin water channels, it
      has become clear that these channels play a crucial role in inner ear fluid
      homeostasis. Indeed, proteins or mRNAs of AQP1, AQP2, AQP3, AQP4, AQP5, AQP6,
      AQP7 and AQP9 are expressed in the inner ear. Many of them are expressed mainly
      in the stria vascularis and the endolymphatic sac, which are the main sites of
      secretion and/or absorption of endolymph. Vasopressin type2 receptor is also
      expressed there. Water homeostasis of the inner ear is regulated in part via the
      arginine vasopressin-AQP2 system in the same fashion as in the kidney, and
      endolymphatic hydrops, a morphological characteristic of Meniere's disease, is
      thought to be caused by mal-regulation of this system. Therefore, aquaporins
      appear to be important for the development of novel drug therapies for Meniere's
      disease and related disorders.

PMID- 19096776
TI  - Role of aquaporin-4 in cerebral edema and stroke.
AB  - Cerebral edema plays a central role in the pathophysiology of many diseases of
      the central nervous system (CNS) including ischemia, trauma, tumors,
      inflammation, and metabolic disturbances. The formation of cerebral edema results
      in an increase in tissue water content and brain swelling which, if unchecked,
      can lead to elevated intracranial pressure (ICP), reduced cerebral blood flow,
      and ultimately cerebral herniation and death. Despite the clinical significance
      of cerebral edema, the mechanism of brain water transport and edema formation
      remain poorly understood. As a result, current therapeutic tools for managing
      cerebral edema have changed little in the past 90 years. "Malignant ischemic
      stroke" is characterized by high mortality (80%) and represents a major clinical
      problem in cerebrovascular disease. Widespread ischemic injury in these patients
      causes progressive cerebral edema, increased ICP, and rapid clinical decline. In
      response to these observations, a series of recent studies have begun to target
      cerebral edema in the management of large ischemic strokes. During cerebral edema
      formation, the glial water channel aquaporin-4 (AQP4) has been show to facilitate
      astrocyte swelling ("cytotoxic swelling"). AQP4 has also been seen to be
      responsible for the reabsorption of extracellular edema fluid ("vasogenic
      edema"). In the present review, the role of AQP4 in the development of cerebral
      edema is discussed with emphasis on its contribution to ischemic edema. We also
      examine the potential of AQP4 as a therapeutic target in edema associated with
      stroke.

PMID- 19096778
TI  - Aquaporins in secretory glands and their role in Sjogren's syndrome.
AB  - Salivary, lacrimal and pancreatic secretions are known to account for multiple
      physiological functions. These exocrine secretions are watery fluids containing
      electrolytes, and a mixture of proteins, and can be stimulated by a number of
      agonists. Since water movement is involved in exocrine secretion, aquaporins
      (AQPs) have been hypothesised to contribute to fluid production in exocrine
      glands. This chapter will focus on the expression, localisation and function of
      AQPs in salivary and lacrimal glands and pancreas. The role of multiple water and
      ion transporters and channels in exocrine fluid secretion will also be reviewed.
      Finally, this chapter will address the potential role of AQPs in Sjogren's
      syndrome.

PMID- 19096779
TI  - Skin aquaporins: function in hydration, wound healing, and skin epidermis
      homeostasis.
AB  - Several aquaporins (AQPs) are expressed in mammalian skin. Some are directly
      involved in water transport, such as AQP5, which is involved in sweat secretion.
      In contrast, the physiological role of skin aquaglyceroporins, which permeate
      both water and glycerol, appears more and more complex. AQP3 is the most abundant
      skin aquaglyceroporin. Both water and glycerol transport by AQP3 appear to play
      an important role in hydration of mammalian skin epidermis. In addition, recent
      data suggest that glycerol transport by AQP3 is involved in the metabolism of
      lipids in skin as well as in the regulation of proliferation and differentiation
      of keratinocytes. Finally, AQP3 is also believed to be important in wound
      healing, as a water channel by facilitating cell migration, and as a glycerol
      transporter by enhancing keratinocyte proliferation and differentiation.

PMID- 19096780
TI  - Function of aquaporin-7 in the kidney and the male reproductive system.
AB  - The aquaporin-7 (AQP7) water channel is known to be a member of the
      aquaglyceroporins, which allow the rapid transport of glycerol and water. In this
      chapter, we review the physiological functions of AQP7 in the kidney and the male
      reproductive system.In the kidney, AQP7 is abundantly present at the apical
      membrane of the proximal straight tubules. Although the contribution of AQP7 to
      the water permeability of proximal straight tubules was found to be minimal
      compared with that of AQP1, we identified a novel glycerol reabsorption pathway
      that may be important for preventing glycerol from being excreted into urine.In
      the male reproductive system, AQP7 is present particularly in the spermatids, as
      well as in the testicular and epididymal spermatozoa, suggesting that AQP7 has
      some role in late spermatogenesis. However, male AQP7 knockout mice were not
      sterile, and their sperm did not show any morphological or functional
      abnormalities.

PMID- 19096781
TI  - Role of aquaporin-7 and aquaporin-9 in glycerol metabolism; involvement in
      obesity.
AB  - The discovery of aquaporin (AQP) has had a great impact on life sciences. So far,
      13 AQPs have been identified in human. AQP3, 7, 9, and 10 are subcategorized as
      aquaglyceroporins which permeabilize glycerol as well as water. Many
      investigators have demonstrated that AQPs play a crucial role in maintaining
      water homeostasis, but the physiological significance of some AQPs as a glycerol
      channel has not been fully understood. Adipocyte is considered to be a major
      source of glycerol which is one of substrates for hepatic gluconeogenesis. This
      review focuses on recent studies of glycerol metabolism through AQP7 and AQP9,
      and discusses the importance of glycerol channel in adipose tissues and liver.

PMID- 19096782
TI  - New members of mammalian aquaporins: AQP10-AQP12.
AB  - Thirteen members of mammalian aquaporins have been identified. Initial ten
      members (AQP-AQP9) are relatively well detailed and their roles are clarified.
      However, the last three members, AQP10-AQP12, are poorly characterized and little
      is known about their roles though they were cloned 6 years ago. In this review,
      we focus on these three AQPs. AQP10 is an aquaglyceroporin while AQP11 and AQP12
      belong to a new subfamily, superaquaporins. Knockout mice for these aquaporins
      are now available. The AQP11 null mouse has a remarkable phenotype, polycystic
      kidneys, which is neonatally fatal. On the other hand, the absence of the other
      two affected little. In some animals, AQP10 is even a pseudogene. This review
      summarizes the current knowledge on these AQPs and will hopefully stimulate
      future research on the subject.

PMID- 19096783
TI  - Structural function of MIP/aquaporin 0 in the eye lens; genetic defects lead to
      congenital inherited cataracts.
AB  - Aquaporin 0 (AQP0) was originally characterized as a membrane intrinsic protein,
      specifically expressed in the lens fibers of the ocular lens and designated MIP,
      for major intrinsic protein of the lens. Once the gene was cloned, an internal
      repeat was identified, encoding for the amino acids Asp-Pro-Ala, the NPA repeat.
      Shortly, the MIP gene family was emerging, with members being characterized in
      mammals, insects, and plants. Once Peter Agre's laboratory developed a functional
      assay for water channels, the MIP family became the aquaporin family and MIP
      became known as aquaporin 0. Besides functioning as a water channel, aquaporin 0
      also plays a structural role, being required for maintaining the transparency and
      optical accommodation of the ocular lens. Mutations in the AQP0 gene in human and
      mice result in genetic cataracts; deletion of the MIP/AQP0 gene in mice results
      in lack of suture formation required for maintenance of the lens fiber
      architecture, resulting in perturbed accommodation and focus properties of the
      ocular lens. Crystallography studies support the notion of the double function of
      aquaporin 0 as a water channel (open configuration) or adhesion molecule (closed
      configuration) in the ocular lens fibers. The functions of MIP/AQP0, both as a
      water channel and an adhesive molecule in the lens fibers, contribute to the
      narrow intercellular space of the lens fibers that is required for lens
      transparency and accommodation.

PMID- 19096784
TI  - pH regulated anion permeability of aquaporin-6.
AB  - The kidney is a model organ for transport physiology (Nielsen 1996). AQPs are
      well-characterized in mammalian kidneys, where they facilitate transepithelial
      water reabsorption. Most renal AQPs are expressed either in proximal tubule cells
      or in collecting duct principal cells, which are known as sites for water
      reabsorption. AQP1 is present in both apical and basolateral membranes of
      proximal tubules, and in descending limbs of Henle's loop where 70% of filtrated
      water is isoosmotically reabsorbed (King and Agre 1996). AQP2 is expressed in
      principal cells of the collecting duct; in response to vasopressin, AQP2
      translocates from intracellular vesicles to the apical plasma membranes, thereby
      increasing water permeability to concentrate urine (Nielsen et al. 1993, 1995;
      Knepper 1997; Schrier 2006). AQP3 and AQP4 reside in the basolateral membranes of
      collecting duct principal cells, where they may provide the exit pathways for
      urine. AQP7, AQP8, and AQP11 are also present in the proximal tubules (Nielsen et
      al. 1998).A rat cDNA clone encoding AQP6 was isolated by PCR-based homologous
      cloning from a rat kidney cDNA library (Ma et al. 1993; Yasui et al. 1999). AQP6
      has high sequence homology to AQP0, AQP2, and AQP5. A human AQP6 was also cloned
      (Ma et al. 1996). Interestingly, the genes encoding AQP2, AQP5, and AQP6 are
      mapped to chromosome band 12q13 as a family gene cluster at this locus (Ma et al.
      1997). Nevertheless, AQP6 is distinct from AQP0, AQP2, and AQP5 in terms of
      function. Among the renal aquaporins mentioned above, AQP6 has a unique
      distribution and a distinct function.

PMID- 19096785
TI  - Aquaglyceroporins and metalloid transport: implications in human diseases.
AB  - Aquaglyceroporin (AQP) channels facilitate the diffusion of a wide range of
      neutral solutes, including water, glycerol, and other small uncharged solutes.
      More recently, AQPs have been shown to allow the passage of trivalent arsenic and
      antimony compounds. Arsenic and antimony are metalloid elements. At physiological
      pH, the trivalent metalloids behave as molecular mimics of glycerol, and are
      conducted through AQP channels. Arsenicals and antimonials are extremely toxic to
      cells. Despite their toxicity, both metalloids are used as chemotherapeutic
      agents for the treatment of cancer and protozoan parasitic diseases. The
      metalloid homeostasis property of AQPs can be a mixed blessing. In some cases,
      AQPs form part of the detoxification pathway, and extrude metalloids from cells.
      In other instances, AQPs allow the transport of metalloids into cells, thereby
      conferring sensitivity. Understanding the factors that modulate AQP expression
      will aid in a better understanding of metalloid toxicity and also provide newer
      approaches to metalloid based chemotherapy.

PMID- 19096786
TI  - Ammonia and urea permeability of mammalian aquaporins.
AB  - The human aquaporins,AQP3,AQP7, AQP8,AQP9, and possibly AQP10, are permeable to
      ammonia, and AQP7, AQP9, and possibly AQP3, are permeable to urea. In humans,
      these aquaporins supplement the ammonia transport of the Rhesus (Rh) proteins and
      the urea transporters (UTs). The mechanism by which ammonium is transported by
      aquaporins is not fully resolved. A comparison of transport equations, models,
      and experimental data shows that ammonia is transported in its neutral form,
      NH(3). In the presence of NH(3), the aquaporin stimulates H(+) transport.
      Consequently, this transport of H(+) is only significant at alkaline pH. It is
      debated whether the H(+) ion passes via the aquaporin or by some external route;
      the investigation of this problem requires the aquaporin-expressing cell to be
      voltage-clamped. The ammonia-permeable aquaporins differ from other aquaporins by
      having a less restrictive aromatic/arginine region, and an exclusively water
      permeable aquaporin can be transformed into an ammonia-permeable aquaporin by
      single point mutations in this region. The ammonia-permeable aquaporins fall into
      two groups: those that are permeable (AQP3, 7, 9, 10) and those that are
      impermeable (AQP8) to glycerol. The two groups differ in the amino acid
      composition of their aromatic/arginine regions. The location of the ammonia
      permeable aquaporins in the body parallels that of the Rh proteins. This applies
      to erythrocytes and to cells associated with nitrogen homeostasis and high rates
      of anabolism. In the liver, AQPs 8 and 9 are found together with Rh proteins in
      cells exposed to portal blood coming from the intestine. In the kidney, AQP3
      might participate in the excretion of NH(4) (+) in the collecting duct. The
      interplay between the ammonia-permeable aquaporins and the other types of ammonia
      and urea-permeable proteins is not well understood.

PMID- 19096788
TI  - Design, synthesis and assaying of potential aquaporin inhibitors.
AB  - The aquaporin protein family performs fundamental tasks in the physiology of
      several organs in the human body. Their roles in several disorders known to
      involve water movement make them attractive targets for the development of novel
      drug therapies.This chapter describes assays commonly used to study the water
      permeability across AQPs. It also describes the effect of some known inhibitors
      of aquaporins on water permeability, such as mercury, gold, silver, copper,
      phloretin, tetraethyl ammonium salts and acetazolamide compounds.

PMID- 19096789
TI  - Aquaporin-1 gene transfer to correct radiation-induced salivary hypofunction.
AB  - Irradiation damage to salivary glands is a common iatrogenic consequence of
      treatment for head and neck cancers. The subsequent lack of saliva production
      leads to many functional and quality-of-life problems for affected patients and
      there is no effective conventional therapy. To address this problem, we developed
      an in vivo gene therapy strategy involving viral vector-mediated transfer of the
      aquaporin-1 cDNA to irradiation-damaged glands and successfully tested it in two
      pre-clinical models (irradiated rats and miniature pigs), as well as demonstrated
      its safety in a large toxicology and biodistribution study. Thereafter, a
      clinical research protocol was developed that has received approval from all
      required authorities in the United States. Patients are currently being enrolled
      in this study.

PMID- 19096787
TI  - Knock-out models reveal new aquaporin functions.
AB  - Knockout mice have been informative in the discovery of unexpected biological
      functions of aquaporins. Knockout mice have confirmed the predicted roles of
      aquaporins in transepithelial fluid transport, as in the urinary concentrating
      mechanism and glandular fluid secretion. A less obvious, though predictable role
      of aquaporins is in tissue swelling under stress, as in the brain in stroke,
      tumor and infection. Phenotype analysis of aquaporin knockout mice has revealed
      several unexpected cellular roles of aquaporins whose mechanisms are being
      elucidated. Aquaporins facilitate cell migration, as seen in aquaporin-dependent
      tumor angiogenesis and tumor metastasis, by a mechanism that may involve
      facilitated water transport in lamellipodia of migrating cells. The '
      aquaglyceroporins', aquaporins that transport both glycerol and water, regulate
      glycerol content in epidermis, fat and other tissues, and lead to a multiplicity
      of interesting consequences of gene disruption including dry skin, resistance to
      skin carcinogenesis, impaired cell proliferation and altered fat metabolism. An
      even more surprising role of a mammalian aquaporin is in neural signal
      transduction in the central nervous system. The many roles of aquaporins might be
      exploited for clinical benefit by modulation of aquaporin expression/function -
      as diuretics, and in the treatment of brain swelling, glaucoma, epilepsy, obesity
      and cancer.

PMID- 19096790
TI  - Cell transplant techniques: engraftment detection of cells.
AB  - The use of isolated human hepatocyte infusions to treat human disease will
      require safe, acceptable, reliable, and reproducible measures of engraftment and
      function of the donor liver cell. Cell transplant for inborn errors of hepatic
      metabolism can be followed by measuring the specific protein missing from the
      recipient, expressed by the transplanted unmodified donor hepatocytes expressing
      the genes in question. This chapter will focus on the clinical techniques
      successful in identifying the engraftment and function of donor human hepatocytes
      when no specific identifiable genes are expressed by donor hepatocytes in acute
      and chronic liver diseases treated by cell infusion. Radiolabeling and dye
      labeling techniques, DNA typing of HLA class I alleles, soluble class I HLA
      ELISA, real-time quantitative PCR techniques including short tandem repeats
      analysis will be detailed and critiqued.

PMID- 19096791
TI  - Hepatocyte transplantation techniques: large animal models.
AB  - The poor hepatocyte engraftment efficiency and the low level of their expansion
      in the host liver are a major limitation to cell therapy for the treatment of
      life-threatening liver diseases. Many rodent models have shown that liver
      repopulation via transplanted hepatocytes occurs only when liver growth capacity
      is impaired for an extended period of time. However, these models are not
      transposable to the clinics and to date there is no safe method to achieve this
      result in a clinical setting.Therefore, it is necessary to define on large animal
      models strategies that provide to transplanted hepatocytes sufficient
      proliferation stimuli to induce their division and that could permit a direct
      extrapolation to humans. Such procedures should be transposable to patients. We
      have defined a protocol of liver partial portal branch embolisation and shown
      that it induces the proliferation of transplanted hepatocytes in non-human
      primates (Macaca mulatta). This animal model is also appropriate to evaluate the
      lentiviral-mediated ex vivo gene therapy approach, since simian hepatocytes are
      efficiently transduced by HIV-1-derived lentivirus vectors.

PMID- 19096792
TI  - Small animal models of hepatocyte transplantation.
AB  - In this chapter, we describe techniques used to determine the efficiency of
      hepatocyte transplantation in animal models of liver disease. We have included
      the Gunn rat as a model of an inherited liver disease without hepatocyte damage
      and Abcb4 knockout mice as a model for an inherited liver disease with hepatocyte
      damage. Immunodeficient mice are included as an animal model for human hepatocyte
      transplantation.We describe problems that can be encountered in the maintenance
      and breeding of Gunn rats and immunodeficient Rag2/gamma common knockout mice.
      Protocols for the collection of bile in rats and mice are described, and we have
      also detailed the detection of green fluorescent protein (GFP)-labelled human
      hepatocytes in immunodeficient mice in this chapter.

PMID- 19096793
TI  - Hepatocyte apoptosis.
AB  - Apoptosis has been documented as a frequent hurdle phenomenon that occurs in
      human hepatocytes during isolation, storage, infusion and after engraftment
      within the recipient liver parenchyma. Apoptosis is an active form of cell death
      that involves programmed cellular machineries leading to a progressive self
      destruction of the cell. In contrary to necrosis, it can affect individual cells
      within a cell population. It is characterized by chronological alteration of
      intracellular biochemical signaling pathways followed by cellular morphological
      changes, DNA fragmentation, perturbation of mitochondrial membrane function and
      changes in the plasma membrane. These cellular alterations can be analyzed using
      different methodologies on adherent, suspended and in situ engrafted hepatocytes.
      This chapter presents a brief overview of these techniques and provides
      methodology for the evaluation of hepatocyte apoptosis at the structural and
      biochemical levels.

PMID- 19096794
TI  - In vitro assays for induction of drug metabolism.
AB  - Hepatic microsomal cytochrome P450 (CYP) forms have a major role in the
      metabolism of drugs and other chemicals. Primary hepatocyte cultures from humans
      and experimental animals are a valuable in vitro system for studying the effects
      of chemicals on CYP forms. This chapter describes methods to evaluate CYP form
      induction in human and rat hepatocytes cultured in a 96-well plate format. The
      use of a 96-well plate format permits studies to be performed with relatively
      small numbers of hepatocytes and obviates the need to harvest cells and prepare
      subcellular fractions prior to the assay of enzyme activities. The induction of
      CYP1A and CYP3A forms in human and rat hepatocytes can be determined by
      measurement of 7-ethoxyresorufin O-deethylase and testosterone 6beta-hydroxylase
      activities, respectively, whereas 7-benzyloxy-4-trifluoromethylcoumarin (BFC) O
      debenzylase can be employed to assess both CYP1A and CYP2B form induction in rat
      hepatocytes. An assay for determining the protein content of hepatocytes cultured
      in a 96-well plate format is also described.

PMID- 19096795
TI  - Liver cell culture techniques.
AB  - Different sources of hepatic tissue, including whole or split livers from organ
      donors or from cadavers, waste liver from therapeutic hepatectomies or small
      sized surgical biopsies, can be successfully used to prepare human hepatocytes
      cultures. The two-step collagenase perfusion remains the most effective way to
      isolate high yields of viable hepatocytes from human liver samples that express
      many typical hepatic functions, among them drug-metabolising (detoxification)
      enzymes, when placed in primary culture. Once isolated, human hepatocytes
      cultured in monolayer in chemically defined conditions (serum-free) survive for
      limited periods of time gradually losing their differentiated phenotype, in
      particular the drug-metabolising enzymes. Supplementation of chemically defined
      media with growth factors, hormones and other specific additives has been used
      with variable success to extend hepatocyte survival and functionality in culture.
      Other culture improvements include the use of extracellular components to coat
      plates or to entrap cells. Conditions for short-term monolayer cultures, allowing
      the maintenance of liver-specific functions for approximately 1 week, are now
      well established. Cultures on plastic dishes coated with extracellular matrix
      components (i.e. Matrigel(TM), collagen, fibronectin or mixture of collagen and
      fibronectin) do meet many of the requirements for short-term incubation
      experiments, without adding too much complexity to the system. Practical details
      on how to carry out these cultures and to assess their functionality (CYP
      activity and ureogenesis) are discussed in this chapter.

PMID- 19096796
TI  - An optimised method for cryopreservation of human hepatocytes.
AB  - Successful cryopreservation of hepatocytes is essential for their use in
      hepatocyte transplantation. Cryopreservation allows hepatocytes to be available
      for emergency treatment of acute liver failure and also for planned treatment of
      liver-based metabolic disorders. In addition, cryopreservation of human
      hepatocytes can facilitate their use in metabolism and toxicity studies.
      Cryopreservation can adversely affect the viability and function, especially
      reduce the attachment efficiency, of hepatocytes on thawing.The cryopreservation
      process can be divided into steps so that improvements can be made on the
      'standard' protocols that are followed in some laboratories. These steps are as
      follows: pre-incubation of cells; freezing solution, cryoprotectants and
      cytoprotectants; freezing process; storage; thawing; post-thawing culture. This
      chapter presents an optimised protocol for cryopreservation of human hepatocytes
      as developed at King's College Hospital.

PMID- 19096797
TI  - Isolation of human hepatocytes.
AB  - Protocols for isolation of human hepatocytes have been developed. The isolated
      cells can be used not only in research but also for transplantation in patients
      with liver disease, especially acute liver failure and liver-based
      metabolic/synthetic conditions. The aim of hepatocyte transplantation is to
      correct the missing liver function(s) and allow either the recovery of the liver
      or buy the patient time until a suitable donor liver is available for
      transplantation.

PMID- 19096798
TI  - Microbiological monitoring of hepatocyte isolation in the GMP laboratory.
AB  - For clinical hepatocyte transplantation, cells need to be prepared in a sterile
      GMP environment. Strict regulations are in place that set the standard for this
      environment that cells are prepared in. These regulations control all aspects of
      the environment. In the United Kingdom, the laboratory must have a licence from
      the Human Tissue Authority to prepare cell for clinical administration. The
      physical parameters such as air quality, pressure, temperature and microbiology
      counts have to be monitored regularly usually through direct measurement.
      Described here are the methods for microbial monitoring of the laboratory
      environment and the isolated cell preparations.

PMID- 19096799
TI  - Liver cell labelling with MRI contrast agents.
AB  - Cell transplantation is a promising approach to improve the life of patients with
      liver disease. At present, however, techniques to track and visualise
      transplanted cells in patients are fairly limited and further development of non
      invasive imaging technology is needed to advance the monitoring of liver cell
      grafts. Magnetic resonance imaging (MRI) is a non-invasive imaging technology
      that already allows the visualisation of particular cell fractions in the liver
      by using MR contrast agents. The use of contrast agents to pre-label liver cells
      prior to transplantation will potentially provide a method to identify, track and
      study the integration of engrafted cells non-invasively by MRI. Before this
      technique can find its clinical application, in vitro and pre-clinical in vivo
      studies need to be conducted to determine the safety and specificity of this
      approach.

PMID- 19096800
TI  - Human intrahepatic biliary epithelial cell lineages: studies in vitro.
AB  - The human intrahepatic biliary epithelium is composed of a morphologically
      heterogeneous population of epithelial cells. During liver cirrhosis, new biliary
      ductular structures develop at the portal margins that express markers of
      immaturity such as CD56 and Bcl-2. These markers are also expressed transiently
      on immature biliary duct precursors during embryological development; thus their
      reappearance during cirrhosis suggests a recapitulation of ontogenesis during
      some liver conditions. Here we describe methods, based on the differential
      expression of membrane markers, for separating immature biliary epithelial cells
      from those associated with mature ducts. We also describe two- and three
      dimensional culture models for the maintenance of mature and immature populations
      in vitro. Both populations readily establish colonies in monolayer culture but
      only cells from mature ducts can be maintained in medium-term culture as serially
      proliferating, passageable cultures; immature cells deteriorate and detach within
      2-3 weeks of isolation. In three-dimensional collagen gel culture, both mature
      and immature populations form duct-like structures with clearly definable lumena
      that persist for up to 6 weeks.

PMID- 19096801
TI  - Isolation, in vitro cultivation and characterisation of foetal liver cells.
AB  - Hepatocyte transplantation has recently become an efficient clinical method in
      the treatment of patients with metabolic liver diseases. The shortage of donor
      cells remains an obstacle to treat more patients. Foetal liver tissues may
      therefore be useful as an alternative source of generating functional hepatocytes
      after in vitro culture and maturation.

PMID- 19096802
TI  - Generation of hepatocytes from human embryonic stem cells.
AB  - Use of human hepatocytes for therapeutic and drug discovery applications is
      hampered by limited tissue source and the inability of hepatocytes to proliferate
      and maintain function long-term in vitro. Human embryonic stem (hES) cells are
      immortal and pluripotent and may provide a cell source for functional human
      hepatocytes (1) Here we have outlined some of the protocols currently in use for
      the generation of hepatocytes from hES cells.

PMID- 19096803
TI  - Production of hepatocyte-like cells from human amnion.
AB  - Cells isolated from the placenta have been the subject of intense investigation
      because many of the cells express characteristics of multipotent or even
      pluripotent stem cells. Cells from the placental tissues such as amnion and
      chorion have been reported to display multilineage differentiation and surface
      marker and gene expression patterns consistent with embryonic stem (ES) and
      mesenchymal stem cells, respectively. We have reported that epithelial cells
      isolated from term placenta contain cells that express surface markers such as
      the stage-specific embryonic antigens (SSEA) and a gene expression profile that
      is similar to ES cells. When subjected to specific differentiation protocols,
      amniotic epithelial cells display markers of differentiation to cardiomyocytes,
      neurons, pancreatic cells and hepatocytes. If specific and efficient methods
      could be developed to induce differentiation of these cells to hepatocytes, the
      amnion may become a useful source of cells for hepatocyte transplants. Cells
      isolated from amnion also have some unique properties as compared to some other
      stem cell sources in that they are isolated from a tissue that is normally
      discarded following birth, they are quite plentiful and easily isolated and they
      do not produce tumors when transplanted. Cells isolated from the amnion may be a
      uniquely useful and noncontroversial stem cell source.

PMID- 19096804
TI  - Sources of adult hepatic stem cells: haematopoietic.
AB  - Bone marrow cells can engraft in the liver and differentiate into a variety of
      cell types including hepatocytes and myofibroblasts. This chapter describes how,
      after transplantation of male bone marrow into female recipients, cells of bone
      marrow origin (male) can be identified in the female liver by virtue of detection
      of the Y chromosome by the technique of in situ hybridisation (ISH). Furthermore,
      ISH for Y chromosome detection can be combined both with immunohistochemistry
      (IHC) to identify phenotype and with ISH for mRNA to demonstrate function.
      Additionally, we show that bone marrow-derived cells can be identified in the
      liver without prior sex-mismatch bone marrow transplantation, identifying instead
      the BCR:ABL fusion gene that is present in all such cells in almost all patients
      suffering from chronic myelogenous leukaemia (CML).

PMID- 19096805
TI  - Ex vivo gene transfer into hepatocytes.
AB  - Ex vivo gene transfer into hepatocytes could serve several purposes in the
      context of gene therapy or cell transplantation: (1) isolated hepatocytes can be
      transduced in culture with therapeutic genes and then transplanted into the
      recipient; (2) marker genes can be introduced for subsequent identification of
      transplanted cells and their progeny; (3) gene transfer can be used for
      conditional immortalization of hepatocytes for expansion in culture; (4)
      immunomodulatory genes can be transferred into hepatocytes to prevent allograft
      rejection. Gene transfer into cultured hepatocytes can be achieved using DNA that
      is not incorporated into recombinant viruses. In such systems, transgene
      integration into the host cell genome can be enhanced using transposon systems,
      such as "sleeping beauty." In addition to using the conventional reagents, such
      as cationic liposomes, DNA transfer into hepatocytes can be achieved by
      Nucleofection or special hepatocyte-targeted carriers such as proteoliposomes
      containing galactose-terminated glycoproteins (e.g. the F protein of the Sendai
      virus). Alternatively, genes can be transferred using recombinant viruses, such
      as adenoviral vectors that are episomal or retroviral vectors (including
      lentiviruses) that permit integration of the transgene into the host genome. Gene
      transfer using lentiviral vectors has been achieved in both attached and
      suspended hepatocytes. Transduction efficiency of lentiviral vectors can be
      enhanced using magnetic nanoparticles (Magnetofection).

PMID- 19096806
TI  - Hepatic preconditioning for transplanted cell engraftment and proliferation.
AB  - Hepatocyte transplantation has therapeutic potential for multiple hepatic and
      extrahepatic disorders with genetic or acquired basis. To demonstrate whether
      cell populations of interest will be effective for clinical applications, it is
      first necessary to characterize their properties in animal systems. Demonstrating
      the potential of cells to engraft and proliferate is a critical part of this
      characterization. Similarly, for stem/progenitor cells, demonstrating the
      capacity to differentiate along appropriate lineages and generate mature cells
      that can engraft and proliferate is essential. In various animal models,
      preconditioning of recipients prior to cell transplantation has been necessary to
      improve engraftment of cells, to stimulate proliferation of engrafted cells, and
      to induce extensive repopulation of the host liver by transplanted cells.
      Although this is an area of active investigation, effective preconditioning
      protocols should alter the hepatic microenvironment, such that transplanted cells
      can obtain selective advantages for engrafting and proliferating in the liver.
      Use of such experimental systems in animals will help generate further strategies
      for liver repopulation and thereby advance clinical applications of liver cell
      therapy.

PMID- 19096807
TI  - Human hepatocyte transplantation overview.
AB  - The interest in hepatocyte transplantation has been growing continuously in
      recent years and this treatment may represent an alternative clinical approach
      for patients with acute liver failure and liver-based metabolic disorders. This
      chapter presents an overview of liver cell transplantation, from the basic
      research to human experience. It summarizes the pre-clinical studies and present
      status of clinical hepatocyte transplantation and identifies some possible areas
      of future research in this area.

PMID- 19096808
TI  - [Indication and performance of endocrine surgery. The significance of molecular
      genetic examination].
AB  - The molecular genetic changes from certain endocrine tumors are already
      understood, reflecting as they do the etiology of these sporadic familial
      disorders. This already has clinical consequences to the treatment of familial
      endocrine tumors, which often appear in the course of syndromatic disorders.
      These consequences consist in slight changes to surgical technique, the search
      for other active and usually endocrinal tumors, and examination of family members
      for other gene carriers (of disease-specific mutations) and the most suitable
      prophylactic tumor therapy. In contrast, for sporadic endocrine tumors there
      exists far less clinically relevant knowledge. Starting with anamnesis and
      clinical findings of active endocrine tumors, we discuss the current
      possibilities for molecular genetic determination of disease-specific mutations
      (germline and tumor DNA) and their effect on surgical procedure.

PMID- 19096809
TI  - [Ulcerated plantar lichen planus. Successful treatment with cyclosporine].
AB  - Plantar ulcerations of lichen planus are unusual manifestations that constrain
      the patient's quality of life and are often refractory to treatment. We report on
      a 71-year-old man in whom a prompt and complete healing of plantar ulcerative
      lichen planus was achieved by treatment with oral cyclosporine.

PMID- 19096810
TI  - [Multiple skin cancers in a patient treated with hydroxyurea].
AB  - A 62-year-old patient treated for 9 years with hydroxyurea for chronic
      myeloproliferative disease developed multiple cutaneous neoplasms. Hydroxyurea
      minimizes DNA synthesis via inhibition of the enzyme ribonucleotide reductase and
      is used to treat hematological malignancies. The most important and severe side
      effect is a dose-dependent myelodepression. An association with multiple skin
      tumors has been reported. The presented case emphasizes this potential risk of
      hydroxyurea therapy. Continuous dermatologic monitoring of patients treated with
      hydroxyurea is recommended.

PMID- 19096811
TI  - [Psychosocial aspects of coping with tinnitus and psoriasis patients. A
      comparative study of suicidal tendencies, anxiety and depression].
AB  - BACKGROUND: Treatment of tinnitus is primarily the task of ENT specialists, while
      treatment of the psychiatric diseases lies in the hand of psychotherapists.
      Different from mostly very apparent dermatological diseases, the severity level
      of tinnitus can often only be determined by psychological test batteries as well
      as a specific psychosomatic exploration. In this study patients with psoriasis
      were compared with tinnitus patients regarding quality of life, anxiety,
      depression and imminent suicidal tendencies, in order to realize the
      psychological impact and find appropriate instruments for treatment. METHODS:
      Between February and April 2005, 89 tinnitus patients, who underwent in-patient
      therapy in a neurootological and psychosomatic hospital, and 105 psoriasis
      patients, who had in-patient treatment from October 1999 until October 2004 in a
      specialized clinic, were examined with psychological tests, which included the
      Tinnitus questionnaire proposed by Goebel und Hiller, the Symptoms Check List of
      Derogatis SCL-90-R, the HADS and the suicide rating according to Poldinger.
      RESULTS: Tinnitus in-patients suffered significantly more from suicidal
      tendencies, depression and anxiety in contrast to patients with psoriasis, who
      suffered more from problems associated with their outward appearance. CONCLUSION:
      The use of a specific psychological test diagnostic is very helpful in the hand
      of the ENT specialist, but the Tinnitus questionnaire of Goebel and Hiller
      enables an initial screening.

PMID- 19096813
TI  - [Important viral and bacterial infections of the skin and mucous membrane].
AB  - Skin infections are more frequent in immunodeficient patients, seniors and
      infants than in healthy individuals with an intact immune system. The severity of
      infections ranges from localized, self-limiting cutaneous infections to
      widespread necrosis of the skin, muscle, and fascia. The most frequent infections
      of the skin and mucous membranes are caused by bacterial and viral infectious
      agents. Fungal infection are also important especially in immunocompromised
      patients. In particular, viruses play an important and increasing role in the
      development of several tumors including HPV-associated cervical, anal and penile
      cancer or HHV-8-induced Kaposi sarcoma.

PMID- 19096814
TI  - [Cutaneous metastases from malignancies which do not originate from the skin. An
      epidemiological study].
AB  - The objective of our study was to get epidemiological data in the region of
      Aarau, Switzerland, about the frequency of cutaneous metastases from visceral
      malignancies. With a computer search we analyzed all patients with skin
      metastases from visceral malignancies who had attended our clinic between January
      1, 1998, and December 31, 2003. Out of 19 491 patients, 37 had cutaneous
      metastases from visceral tumours (0,19%): 25 women (67.5%) and 12 men (32.5%)
      were affected. 19 had breast cancer (51%), 8 sarcomas (21%), 2 leukemia (5%), 2
      colorectal cancer, and one each ovary carcinoma, bronchial cancer, prostate
      cancer, malignant histiocytoma and Non-Hodgkin lymphoma (3%). In 24 cases the
      primary malignancy was known (65%). In 35% cutaneous metastases were diagnosed at
      the same time as the primary tumour. Primary malignancies were diagnosed in 54%
      within the age range of 50-70 years, and 65% of cutaneous metastases were
      diagnosed within the age range of 50-80 years. In 51% skin metastases were the
      first site of dissemination. In 49% other known metastases were present (5%
      locoregional, 38% lymph nodes, 3% brain, 3% lung, 3% liver). Our study documents
      that cutaneous metastases from visceral malignancies are rare. However, early
      diagnosis has an impact concerning further treatment and prognosis.

PMID- 19096815
TI  - [Skin signs of systemic diseases].
AB  - Many aspects of cutaneous signs are of importance to nondermatologists, as skin
      manifestations can reflect internal disease states, either directly or as a
      result of a complication or treatment and therefore can lead to the diagnosis of
      systemic illness. Serious morbidity and mortality can be avoided by early
      recognition of only minor cutaneous manifestations signaling internal problems.
      Limited forms of collagen vascular disease exemplify the important marker
      function of the skin for diagnosis as well as for prognosis with their typically
      favorable course permitting a less aggressive treatment. The utmost important
      prerequisite of diagnosing skin conditions is an accurate and thorough
      examination of the skin, the adjacent mucous membranes and the integumentary
      appendages. In a first step, the primary site of the cutaneous condition should
      be identified (e.g. epidermal, dermal or subdermal) and then the form, the
      pattern, and distribution should be recognized. There are many comprehensive and
      excellent textbooks available for guidance. This article focuses on the more
      common dermatologic conditions linked to different organ systems involved
      (excluding infectious diseases, metabolic diseases and drug induced conditions).

PMID- 19096816
TI  - [Hypertension in patients with renal artery stenosis].
AB  - Renal artery stenosis (RAS) is often present in patients with severe hypertension
      and atherosclerotic vascular disease. In this setting it is important to screen
      patients for renovascular disease, e.g. with Duplex-ultrasound, CT- or MR
      angiography. The challenge of treating these patients is to find the evidence
      proving that the RAS is responsible for hypertension and/or renal dysfunction.
      Measurement of the intra-arterial pressure gradient is necessary in order to
      determine hemodynamic relevance. On the other side, in these patients
      hypertension is often of primary and/or renoparenchymatous origin and is
      aggravated by a renovascular disease. This explains why hypertension cannot be
      cured even if a high grade stenosis has been removed. In addition, thromb- and
      cholesterol-embolic material is often mobilized during an invasive procedure and
      leads to renaparenchymatous ischemia which sustains hypertension after
      intervention. An individual evaluation of profit versus risk is important for the
      decision for or against an invasive procedure, especially since there is no
      sufficient evidence for a decrease of mortality after interventions of RAS. The
      optimal conservative treatment, including the treatment of atherosclerotic risk
      factors is recommended.

PMID- 19096817
TI  - [Glucocorticoids and hypertension].
AB  - Severe arterial hypertension is a hallmark of Cushing syndrome which occurs in
      80% of the patients. Additionally, persistent cortisol excess induces obesity,
      hyperinsulinemia with disturbed glucose tolerance and dyslipidemia which all
      contribute to the development of hypertension and its deleterious sequelae.
      Cortisol effects are mediated through diversely distributed intracellular
      glucocorticoid and mineralocorticoid receptors which are protected by the 11-beta
      hydroxysteroiddehydrogenase type 2 in cells of some organs (i.e. kidney) but not
      in other. A highly complex clinical picture evolves in case of hypercortisolism
      due to the ubiquitous distribution of steroid receptors with different affinity
      and binding capacities for glucocorticoids. The present review focuses on the
      cortisol induced changes in blood pressure regulation which contribute to the
      development of hypertension.

PMID- 19096818
TI  - Lysosomal cysteine peptidase cathepsin L protects against cardiac hypertrophy
      through blocking AKT/GSK3beta signaling.
AB  - The lysosomal cysteine peptidase cathepsin L (CTSL) is an important lysosomal
      proteinase involved in a variety of cellular functions including intracellular
      protein turnover, epidermal homeostasis, and hair development. Deficiency of CTSL
      in mice results in a progressive dilated cardiomyopathy. In the present study, we
      tested the hypothesis that cardiac overexpression of human CTSL in the murine
      heart would protect against cardiac hypertrophy in vivo. The effects of
      constitutive human CTSL expression on cardiac hypertrophy were investigated using
      in vitro and in vivo models. Cardiac hypertrophy was produced by aortic banding
      (AB) in CTSL transgenic mice and control animals. The extent of cardiac
      hypertrophy was quantitated by two-dimensional and M-mode echocardiography as
      well as by molecular and pathological analyses of heart samples. Constitutive
      overexpression of human CTSL in the murine heart attenuated the hypertrophic
      response, markedly reduced apoptosis, and fibrosis. Cardiac function was also
      preserved in hearts with increased CTSL levels in response to hypertrophic
      stimuli. These beneficial effects were associated with attenuation of the
      Akt/GSK3beta signaling cascade. Our in vitro studies further confirmed that CTSL
      expression in cardiomyocytes blunts cardiac hypertrophy through blocking of
      Akt/GSK3beta signaling. The study indicates that CTSL improves cardiac function
      and inhibits cardiac hypertrophy, inflammation, and fibrosis through blocking
      Akt/GSK3beta signaling.

PMID- 19096820
TI  - [3D navigated osteosynthesis of calcaneal fractures. Open and minimally invasive
      techniques].
AB  - BACKGROUND: It is hypothesized that misplacement of sustentacular screws during
      osteosynthesis of intraarticular calcaneal fractures can be reduced with the help
      of navigation. A method for three-dimensional (3D) navigated placement of
      sustentacular screws for treating intraarticular calcaneal fractures is presented
      and evaluated. MATERIAL AND METHODS: 11 consecutive patients with 15
      intraarticular calcaneal fractures were treated using 3D navigation. In 12 cases
      osteosynthesis was done through an extended lateral approach; in three cases, it
      was achieved through a minimally invasive percutaneous approach. For verification
      and documentation of the placed screws, a second 3D scan was performed. RESULTS:
      A total of 20 screws were placed using 3D navigation. None of the navigated
      screws was misplaced. Extra operating time due to navigation averaged 11.9
      minutes (+/-2.2 min). CONCLUSION: Through a combination of intraoperative 3D
      imaging and navigation, placement of sustentacular screws is possible and can
      yield precise and reliable results. Especially in minimally invasive treatment, a
      high quality of osteosynthesis can be achieved.

PMID- 19096821
TI  - [Persistent dysphagia and mechanical glottic paralysis. Complications of a
      ventral fracture spondylodesis with Forestier's disease].
AB  - Persistent dysphagia after ventral instrumentation of a patient with a cervical
      spine fracture and diffuse idiopathic skeletal hyperostosis (DISH, or Forestier's
      disease) is a rare but dramatic complication. In this case report some
      pathogenetic factors are discussed. Accurate resection of the spondylophytes
      should be considered to avoid a ventral protrusion of the plate.

PMID- 19096822
TI  - [Radiotherapy of lymph node metastases].
AB  - Radiotherapy of lymph node stations with clinical or subclinical disease can
      markedly reduce the risk of recurrence in these regions. The therapeutic gain
      depends on multiple concurrent risks, the underlying risk of recurrence in the
      respective lymph node station, the risk reduction by radiotherapy, the risk of
      local relapse of the primary tumor, the risk of distant metastases, and the risks
      of side effects of the therapy. An overview of the evidence from randomized
      studies on radiotherapy of lymph node regions is given.

PMID- 19096823
TI  - Hyperglycaemia is associated with changes in the regional concentrations of
      glucose and myo-inositol within the brain.
AB  - AIMS/HYPOTHESIS: The aim of the study was to assess the effect of hyperglycaemia
      on regional concentrations of glucose and other substrates within the brain in
      non-diabetic individuals and in patients with type 1 diabetes. METHODS: The brain
      metabolites of 17 men with type 1 diabetes and 12 age-matched non-diabetic men
      (22-43 years old) were studied after an overnight fast (plasma glucose 9.2 +/-
      3.0 vs 4.8 +/- 0.5 mmol/l, respectively). N-Acetylaspartate (NAA), creatine,
      choline, myo-inositol (mI) and glucose in the frontal cortex, frontal white
      matter and thalamus were quantified with proton magnetic resonance spectroscopy.
      RESULTS: In the non-diabetic participants, the glucose level was 47% higher (p <
      0.01) in the frontal cortex than in the frontal white matter. In contrast, this
      regional variation was not observed in the diabetic participants, in whom the
      glucose level in the frontal white matter was 64% higher (p < 0.001) and in the
      frontal cortex 25% higher (p = 0.033) than that of the non-diabetic participants.
      In the diabetic participants, the glucose level in each of the three regions
      studied correlated with fasting plasma glucose (r = 0.88-0.67, p < 0.01). In
      addition, in the diabetic participants, mI was 20% higher (p < 0.001) and NAA 6%
      lower (p = 0.037) in the frontal white matter, and mI was 8% higher (p = 0.042)
      in the frontal cortex, than in the non-diabetic participants.
      CONCLUSIONS/INTERPRETATION: In type 1 diabetes, hyperglycaemia is associated with
      accumulation of glucose and mI in the cortex and in the white matter.

PMID- 19096824
TI  - Ghrelin-producing epsilon cells in the developing and adult human pancreas.
AB  - AIMS/HYPOTHESIS: While the mechanisms of specification and the reciprocal
      relationships of the four types of endocrine cell (alpha, beta, delta and
      pancreatic polypeptide cells) within the human endocrine pancreas are well
      described in adults and during fetal development, ghrelin-immunoreactive cells
      (epsilon cells) remain poorly understood. METHODS: We studied epsilon cells in 24
      human fetal pancreases between 11 and 39 weeks of development and in 32
      pancreases from adult organ donors. RESULTS: We observed single epsilon cells
      scattered in primitive exocrine tissue from gestational week 13 in developing
      pancreas. Later in the developmental process, epsilon cells started to aggregate
      into clusters. From gestational week 21, epsilon cells were observed located
      around developing islets, forming an almost continuous layer at the peripheral
      rim of the islets. They remain localised on the mantle of the islets, although at
      different amounts, in the adult pancreas. Co-production of ghrelin with insulin,
      glucagon or somatostatin was not detected during fetal development. Co-production
      with pancreatic polypeptide was evident sporadically. Epsilon cells co-produced
      NK2 homeobox 2 and ISL LIM homeobox 1, but not NK6 homeobox 1 and paired box 6. A
      quantitative analysis was performed in the adult pancreas: there was an average
      of 1.17 + 1.17 epsilon cells per islet, the relative epsilon cell volume was 0.14
      + 0.16% and the epsilon cell mass was 0.13 + 0.15 g. Neither sex nor age affected
      the epsilon cell mass, although there was a significant inverse correlation with
      BMI. CONCLUSIONS/INTERPRETATION: During fetal development epsilon cells show an
      ontogenetic and morphogenetic pattern that is distinct from that of alpha and
      beta cells.

PMID- 19096825
TI  - [Arthropathy of instability. Causes, treatment options and results].
AB  - Glenohumeral arthritis may develop after primary or recurrent shoulder
      dislocation or after surgery for stabilization. Postoperatively, the incidence is
      reported to be from 12% to 62%, depending on different risk factors. There is no
      certain correlation between the surgical technique and the rate of arthrosis.
      Capsulorraphy arthropathy is biomechanically and clinically a well defined
      entity. The risk of developing severe arthrosis of the shoulder following
      dislocation of the shoulder is between 10 and 20 times greater in comparison to
      the normal population. Risk factors are the age during the first episode of
      instability, the age at instability surgery, bony lesions on the humeral head or
      the glenoid and rotator cuff tears.For mild stages of glenohumeral arthritis,
      arthroscopic revision with removal of intraarticular metallic parts, arthroscopic
      debridement or arthroscopic arthrolysis of an internal rotation contracture might
      be sufficient. For more severe stages mobilization of the internal rotation
      contracture and glenohumeral arthroplasty are indicated. With sufficient
      integrity of the head and glenoid, a surface replacement is adequate. With intact
      rotator cuff and without bone graft the results for shoulder arthroplasty are
      comparable to those following primary omarthrosis. With a bone graft at the
      glenoidal side the risk for implant loosening is 10 times greater. For the
      functional outcome the quality of the rotator cuff, i.e. the fatty degeneration,
      is more predictive than the type of previous surgery or the preoperative external
      rotation contracture.

PMID- 19096826
TI  - [Open and arthroscopic procedures for posterior shoulder instability].
AB  - Posterior instability is less common than anterior shoulder instability and
      diagnosis and treatment are more difficult and complex. This review article gives
      an overview on diagnostics, classification and the influence on therapy.
      Furthermore different arthroscopic and open procedures are presented and the
      surgical techniques are described in detail.

PMID- 19096827
TI  - Genetic analysis of the role of the ABC transporter Ota and Otb in glycine
      betaine transport in Methanosarcina mazei Go1.
AB  - The methanogenic archaeon Methanosarcina mazei Go1 accumulates glycine betaine in
      response to hypersalinity but differs from most other methanoarchaea in having
      two gene clusters both encoding a potential glycine betaine transporter, Ota and
      Otb. We have created mutants with either ota or otb deleted to address their role
      in salt adaptation. The mutants were not impaired in growth at low or high salt,
      neither at 37 degrees C nor at lower temperatures. However, the Deltaota mutant
      was completely defective in glycine betaine transport demonstrating that Ota is
      the only glycine betaine transporter in M. mazei. The mutation in otb led to
      increased transcription of ota and thus increased transport and accumulation of
      glycine betaine suggesting a cross talk between the two transporters.

PMID- 19096828
TI  - Uranium induces apoptosis in lung epithelial cells.
AB  - Uranium is a naturally occurring radioactive material present everywhere in the
      environment. It is toxic because of its chemical or radioactive properties.
      Uranium enters environment mainly from mines and industry and cause threat to
      human health by accumulating in lungs as a result of inhalation. In our previous
      study, we have shown the effectiveness of antioxidant system response to the
      oxidative stress induced by uranyl acetate (UA) in rat lung epithelial (LE)
      cells. As part of our continuing studies; here, we investigated the mechanism
      underlying when LE cells are exposed to different concentration of UA. Oxidative
      stress may lead to apoptotic signaling pathways. LE cells treated with 0.25, 0.5
      and 1 mM of UA results in dose and time-dependent increase in activity of both
      caspases-3 and -8. Increase in the concentration of cytochrome-c oxidase in
      cytosol was seen in LE cells treated with 1 mM UA as a result of mitochondria
      membrane permeability. The cytochrome-c leakage may trigger the apoptotic
      pathway. TUNEL assay performed in LE cells treated with 1 mM of UA showed
      significant incorporation of dNTPs in the nucleus after 24 h. In the presence of
      the caspase inhibitors, we observed the significant decrease in the activity of
      caspases-8 and -3 in 0.5 and 1 mM UA-treated LE cells.

PMID- 19096830
TI  - A capacitive biosensor for detection of staphylococcal enterotoxin B.
AB  - A sensitive method for the detection of staphylococcal enterotoxin B (SEB) using
      a flow-injection capacitive biosensor is presented. SEB was purified from a crude
      culture filtrate of Staphylococcus aureus through three chromatographic steps.
      The first two steps were based on ion-exchange chromatography, and the last step
      was carried out on a gel filtration column. The SEB recovery values after the
      purification stages were 88%, 74%, and 12%, respectively. A horseradish
      peroxidase labeled antistaphylococcal enterotoxin B was prepared by the periodate
      method and was further employed in a sandwich-enzyme-linked immunosorbent assay
      (ELISA) for the determination of SEB concentrations in different samples obtained
      during the processing of the crude filtrate. The capacitive biosensor could
      detect SEB concentrations as low as 0.3 pg ml(-1) with a linearity ranging from
      2.8 pg ml(-1) to 2.8 ng ml(-1) under optimized conditions. The response time was
      about 10 min. A good agreement was achieved between the developed capacitive
      biosensor system and ELISA as a reference method for detection of SEB levels in
      different purification samples. The newly developed sensor has the benefits of
      simplicity, high sensitivity, and multiple use capability.

PMID- 19096829
TI  - Differential susceptibility to ethanol and amphetamine sensitization in dopamine
      D3 receptor-deficient mice.
AB  - RATIONALE: Dopamine D3 receptors (D3Rs) have been implicated in behavioral
      sensitization to various drugs of abuse, but their role in ethanol (EtOH)
      sensitization has not been directly examined. We used D3R knockout (D3 KO) mice
      to examine whether the D3R plays a permissive role in EtOH and amphetamine (AMPH)
      sensitization. We also investigated whether EtOH sensitization is accompanied by
      alterations in D3R mRNA expression or binding. MATERIALS AND METHODS: After
      comparing EtOH sensitization in C57Bl/6 mice and DBA/2 mice, D3 KO, wild type
      (WT), and for comparison, D1 and D2 KOs received five biweekly injections of EtOH
      (2.2 g/kg, i.p.) or saline. Another group of D3 KOs and WT controls received six
      times AMPH (1.5 mg/kg, i.p.). D3R mRNA and binding were measured in EtOH
      sensitized DBA/2 mice with in situ hybridization and [(125)I]-7-OH-PIPAT
      autoradiography, respectively. RESULTS: C57Bl/6 mice expressed EtOH sensitization
      albeit to a lesser extent than DBA/2 mice. Compared to WT mice, D3 KOs were
      resistant to EtOH sensitization. The behavioral profile of D3 KOs was more
      similar to D1 KOs than D2 KOs, which also failed to develop EtOH sensitization.
      However, D3 KOs developed AMPH sensitization normally. EtOH sensitization was not
      accompanied by changes in either D3R mRNA or D3R binding in the islands of
      Calleja, nucleus accumbens, dorsal striatum, or cerebellum. CONCLUSIONS: These
      results suggest a necessary role for the D3R in EtOH but not AMPH sensitization,
      possibly through postreceptor intracellular mechanisms. Results also suggest that
      different neurochemical mechanisms underlie sensitization to different drugs of
      abuse.

PMID- 19096831
TI  - Quantitative analysis of DHEA and androsterone in female urine: investigating the
      effects of menstrual cycle, oral contraception and training on exercise-induced
      changes in young women.
AB  - Dehydroepiandrosterone (DHEA) and its metabolite androsterone (A) are natural
      steroids secreted in high quantities in human body. To assess the influence of
      oral contraceptives, menstrual cycle phase, and also physical exercise (acute and
      chronic such as training) on these metabolites excretions, a collection of 28
      female urine specimens was organized. A three-extraction-step method was
      developed, and the analyses were performed by gas chromatography-mass
      spectrometry using deuterated 19-noretiocholanolone as the internal standard.
      Sample hydration state was found to be of great importance for kinetic studies,
      as it directly influenced the concentrations. No influence of menstrual cycle and
      training was found for androsterone and DHEA. However, oral contraceptive intake
      lowered DHEA excretion in urine and A seems to be slightly affected by exercise.

PMID- 19096832
TI  - A new procalcitonin optical immunosensor for POCT applications.
AB  - A new immunosensor for the determination of procalcitonin was developed. A
      sandwich assay format was implemented on a polymethylmetacrylate optical biochip,
      opportunely shaped in order to obtain several flow channels and potentially
      suitable for point of care testing applications. The sandwich format makes use of
      two new rat monoclonal antibodies. The capture antibody was covalently
      immobilised on the surface of the plastic chip, and the detection antibody was
      labelled with DY647 dye. Different combinations of capture and detection
      antibodies were investigated, and particular attention was devoted in order to
      avoid the non-specific adsorption. A limit of detection of 0.088 mg L(-1) was
      achieved within the working range of 0.28-50 mg L(-1) in buffer samples. The
      assay was also implemented in human serum, and 0.2 and 0.7-25 mg L(-1) were the
      attained limit of detection and working range, respectively.

PMID- 19096833
TI  - Determination of viable Escherichia coli using antibody-coated paramagnetic beads
      with fluorescence detection.
AB  - A rapid and convenient assay system was developed to detect viable Escherichia
      coli in water. The target bacteria were recovered from solution by immunomagnetic
      separation and incubated in tryptic soy broth with isopropyl-beta-D
      thiogalactopyranoside, which induces formation of beta-galactosidase in viable
      bacteria. Lysozyme was used to lyse E. coli cells and release the beta
      galactosidase. Beta-galactosidase converted 4-methylumbelliferyl-beta-D
      galactoside to 4-methylumbelliferone (4-MU), which was measured by fluorescence
      spectrophotometry using excitation and emission wavelengths of 355 and 460 nm,
      respectively. Calibration graphs of 4-MU fluorescence intensity versus E. coli
      concentration showed a detection range between 8 x 10(4) and 1.6 x 10(7) cfu mL(
      1), with a total analysis time of less than 3 h. The advantage of this method is
      that it detects viable cells because it is based on the activity of the enzyme
      intrinsic to live E. coli.

PMID- 19096834
TI  - Task-specific modulation of multi-digit forces to object texture.
AB  - During multi-digit grasping both local and non-local digit force responses occur
      in response to changes in texture at selected digits depending on the grasp
      configuration. However, the extent to which the specific patterns of force
      distribution depend on the requirement to hold the object against gravity remains
      to be determined. In the present study, we examined whether grasp force sharing
      patterns are invariant when the constraint of maintaining the object orientation
      vertical against gravity is removed. We used changes in object texture to elicit
      force changes at single digits during two grasping tasks with different
      behavioral contexts. One task entailed holding an object against gravity (object
      hold [OH]). A second (force production [FP]) task consisted of generating lifting
      forces on an object clamped to the tabletop that were matched to those used
      during OH. Unlike OH, the FP task lacks the behavioral consequences associated
      with erroneous sharing of normal and tangential digit forces, e.g., object tilt.
      Ten subjects lifted and simulated lifting an instrumented object measuring
      grasping normal and vertical tangential forces at all five digits when the
      textures were uniformly high-friction sandpaper or low-friction rayon and when
      one digit contacted a different frictional texture than the other four digits. We
      found that in both tasks texture changes at individual digits elicited force
      changes at that digit as well as other digits. However, the specific pattern of
      force distribution changes differed during OH compared to FP. While subjects
      modulate the normal and tangential digit forces to different degrees depending on
      object texture and the grasping task, they ignore the requirement of moment
      equilibrium when this has no consequences on object orientation (FP task). These
      findings indicate that multi-digit force responses to texture revealed by
      previous studies are not obligatory and suggest that the behavioral context of a
      task should be considered when inferring general principles of multi-digit force
      coordination.

PMID- 19096836
TI  - Sampling density for the quantitative evaluation of air trapping.
AB  - BACKGROUND: Concerns have been expressed recently about the radiation burden on
      patient populations, especially children, undergoing serial radiological testing.
      To reduce the dose one can change the CT acquisition settings or decrease the
      sampling density. OBJECTIVE: In this study we determined the minimum desirable
      sampling density to ascertain the degree of air trapping in children with cystic
      fibrosis. MATERIALS AND METHODS: Ten children with cystic fibrosis in stable
      condition underwent a volumetric spiral CT scan. The degree of air trapping was
      determined by an automated algorithm for all slices in the volume, and then for
      1/2, 1/4, to 1/128 of all slices, or a sampling density ranging from 100% to 1%
      of the total volume. The variation around the true value derived from 100%
      sampling was determined for all other sampling densities. RESULTS: The precision
      of the measurement remained stable down to a 10% sampling density, but decreased
      markedly below 3.4%. CONCLUSION: For a disease marker with the regional
      variability of air trapping in cystic fibrosis, regardless of observer
      variability, a sampling density below 10% and even more so, below 3.4%,
      apparently decreases the precision of the evaluation.

PMID- 19096835
TI  - Harmonic voiding urosonography with a second-generation contrast agent for the
      diagnosis of vesicoureteral reflux.
AB  - BACKGROUND: Voiding urosonography with harmonic imaging (VUS HI) has been
      introduced as a sensitive and radiation-free imaging method for the diagnosis and
      follow-up of vesicoureteral reflux (VUR) in children. OBJECTIVE: The purpose of
      this study was to evaluate the sensitivity of VUS HI using a second-generation US
      contrast agent compared to standard voiding cystourethrography (VCUG). MATERIALS
      AND METHODS: A total of 228 children with 463 kidney-ureter units (KUUs)
      underwent two cycles of VUS HI and two cycles of VCUG at the same session. VUS HI
      was performed after intravesical administration of 1 ml of a second-generation US
      contrast agent (sulphur-hexafluoride gas microbubbles, SonoVue, Bracco, Italy).
      For statistical analysis we used McNemar's test, Student's t-test and k
      coefficient tests. RESULTS: VUR was shown in 161/463 (34.7%) KUUs, 57 by both
      methods, 90 only by VUS, and 14 only by VCUG. Concordance in findings regarding
      the presence or absence of VUR was found in 359/463 (77.5%) KUUs (k=0.40). The
      difference in the detection rate of reflux between the two methods was
      significant (P<0.01). More importantly, reflux missed by VCUG was of higher grade
      (2 grade I, 65 grade II, 19 grade III, 4 grade IV) than that missed by VUS (8
      grade I, 5 grade II, 1 grade III). CONCLUSION: VUS HI and a second-generation
      contrast agent improved the identification of reflux in children. Our data reveal
      a higher sensitivity of the method compared to VCUG. Thus it can be used as an
      alternative radiation-free imaging method.

PMID- 19096837
TI  - Simultaneous flue gas bioremediation and reduction of microalgal biomass
      production costs.
AB  - A flue gas originating from a municipal waste incinerator was used as a source of
      CO(2) for the cultivation of the microalga Chlorella vulgaris, in order to
      decrease the biomass production costs and to bioremediate CO(2) simultaneously.
      The utilization of the flue gas containing 10-13% (v/v) CO(2) and 8-10% (v/v)
      O(2) for the photobioreactor agitation and CO(2) supply was proven to be
      convenient. The growth rate of algal cultures on the flue gas was even higher
      when compared with the control culture supplied by a mixture of pure CO(2) and
      air (11% (v/v) CO(2)). Correspondingly, the CO(2) fixation rate was also higher
      when using the flue gas (4.4 g CO(2) l(-1) 24 h(-1)) than using the control gas
      (3.0 g CO(2) l(-1) 24 h(-1)). The toxicological analysis of the biomass produced
      using untreated flue gas showed only a slight excess of mercury while all the
      other compounds (other heavy metals, polycyclic aromatic hydrocarbons,
      polychlorinated dibenzodioxins and dibenzofurans, and polychlorinated biphenyls)
      were below the limits required by the European Union foodstuff legislation.
      Fortunately, extending the flue gas treatment prior to the cultivation unit by a
      simple granulated activated carbon column led to an efficient absorption of
      gaseous mercury and to the algal biomass composition compliant with all the
      foodstuff legislation requirements.

PMID- 19096838
TI  - Cell wall adaptations of planktonic and biofilm Rhodococcus erythropolis cells to
      growth on C5 to C16 n-alkane hydrocarbons.
AB  - Rhodococcus erythropolis was found to utilize C5 to C16 n-alkane hydrocarbons as
      sole source of carbon and energy when growing as planktonic or biofilm cells
      attached to polystyrene surfaces. Growth rates on even numbered were two- to
      threefold increased relatively to odd-numbered n-alkanes and depended on the
      chain length of the n-alkanes. C10-, C12-, C14-, and C16-n-alkanes gave rise to
      two- to fourfold increased maximal growth rates relative to C5- to C9
      hydrocarbons. In reaction to the extremely poor water solubility of the n
      alkanes, both planktonic and biofilm cells exhibited distinct adaptive changes.
      These included the production of surface active compounds and substrate-specific
      modifications of the physicochemical cell surface properties as expressed by the
      microbial adhesion to hydrocarbon- and contact angle-based hydrophobicity, as
      well as the zeta potential of the cells. By contrast, n-alkane-specific
      alterations of the cellular membrane composition were less distinct. The
      specificity of the observed autecological changes suggest that R. erythropolis
      cells may be used in the development and application of sound biocatalytic
      processes using n-alkanes as substrates or substrate reservoirs or for target
      specific bioremediation of oils and combustibles, respectively.

PMID- 19096839
TI  - Anatomy of the subtalar joint and imaging of talo-calcaneal coalition.
AB  - Talo-calcaneal coalitions may be intra-articular or extra-articular in position
      and may be classified as fibrous, cartilaginous or osseous in morphology. Fibrous
      coalitions, particularly extra-articular talo-calcaneal coalitions, may have
      cross-sectional imaging findings that resemble normal anatomic variants,
      particularly the medial talo-calcaneal ligament and to a lesser extent the
      presence of an accessory articular facet between the posterior margin of the
      sustentaculum and postero-medial process of the talus. Typically, in the adult
      fibrous coalition, there will be some osseous deformity at the entheses, allowing
      differentiation from a medial talo-calcaneal ligament. The anatomy of the
      subtalar joint and its ligamentous supports, normal anatomic variations and their
      corresponding imaging appearance are reviewed in the first part of this article.
      In the second part, the various forms of talo-calcaneal coalition and their
      imaging appearance are reviewed.

PMID- 19096840
TI  - Relationship of Modic type 1 change with disc degeneration: a prospective MRI
      study.
AB  - OBJECTIVE: The objective was to study the natural course of Modic type 1 change
      (M1) in relation to lumbar disc degeneration. MATERIALS AND METHODS: Twenty-four
      chronic low back pain (LBP) patients with M1 on lumbar spine were selected from
      1,015 patients with magnetic resonance imaging from a follow-up study lasting for
      18-74 months. Exclusion criteria were any other specific back disorder, age
      >or=60 years, or a recent spine operation. The association between the
      development of M1 and degenerative disc changes was studied using multivariate
      modeling (complex samples logistic regression). RESULTS: At baseline, 20 of 28
      (71%) disc spaces with M1 had a decreased disc height (DH) and 16 of 28 (57%) a
      dark nucleus pulposus, but ten of 28 (36%) a very dark annulus fibrosus and a
      paradoxically bright nucleus pulposus albeit decreased DH. During follow-up, DH
      decreased in 13 of 28 (46%) and signal intensity of nucleus pulposus (DSI) in
      eight of 28 (29%) disc spaces with M1, but it increased in four (14%) discs. In
      those without M1, only few changes occurred. The larger the M1, the more likely
      was the DH low or decreased further. Both the presence and changes in M1 were
      associated with a decrease in DH and changes in DSI and bulges. CONCLUSION: The
      degenerative process in discs with adjacent M1 seems to be accelerated and leads
      to advanced and deforming changes with special morphologic features. M1 may be a
      sign of a pathologic degenerative process in the discovertebral unit.

PMID- 19096841
TI  - Comparison of subcutaneous and intraperitoneal injection of D-luciferin for in
      vivo bioluminescence imaging.
AB  - PURPOSE: We compared subcutaneous (SC) injection and intraperitoneal (IP)
      injection of D-luciferin for in vivo bioluminescence imaging (BLI) to determine
      the utility of SC injection. METHODS: Mice bearing SC tumours stably expressing
      firefly luciferase underwent in vivo BLI using SC and IP injection of D: 
      luciferin. BLI studies were repeated at an interval of 3 h using a given
      injection route to assess repeatability and using different injection routes to
      assess correlation. In mice bearing both SC and IP tumours, BLI was performed
      successively using intravenous (IV), SC, and IP injection of D: -luciferin.
      Haematological malignancy model mice underwent BLI using SC and IP injection.
      RESULTS: In SC tumours, the peak time was slightly shorter and the peak signal
      was greater using SC injection than using IP injection. The repeatability of
      determining peak signals was comparable between the two injection routes, and a
      good correlation was observed between them. In mice bearing both SC and IP
      tumours, signals from IP tumours relative to those from SC tumours were much
      greater using IP injection than using IV or SC injection. In the haematological
      malignancy model, signals from the spleen relative to those from the bone marrow
      were greater using IP injection than using SC injection. CONCLUSION: In addition
      to rare injection failure, the IP injection of D: -luciferin led to the
      overestimation of signals from IP tissues. For BLI, SC injection was shown to be
      a convenient alternative to IP injection.

PMID- 19096842
TI  - Bone marrow involvement in diffuse large B-cell lymphoma: correlation between FDG
      PET uptake and type of cellular infiltrate.
AB  - PURPOSE: To assess, in patients with diffuse large B-cell lymphoma (DLBCL),
      whether the low sensitivity of (18)F-fluorodeoxyglucose positron emission
      tomography (FDG-PET) for bone marrow assessment may be explained by histological
      characteristics of the cellular infiltrate. METHODS: From a prospective cohort of
      110 patients with newly diagnosed aggressive lymphoma, 21 patients with DLBCL had
      bone marrow involvement. Pretherapeutic FDG-PET images were interpreted visually
      and semiquantitatively, then correlated with the type of cellular infiltrate and
      known prognostic factors. RESULTS: Of these 21 patients, 7 (33%) had lymphoid
      infiltrates with a prominent component of large transformed lymphoid cells
      (concordant bone marrow involvement, CBMI) and 14 (67%) had lymphoid infiltrates
      composed of small cells (discordant bone marrow involvement, DBMI). Only 10
      patients (48%) had abnormal bone marrow FDG uptake, 6 of the 7 with CBMI and 4 of
      the 14 with DBMI. Therefore, FDG-PET positivity in the bone marrow was
      significantly associated with CBMI, while FDG-PET negativity was associated with
      DBMI (Fisher's exact test, p=0.024). There were no significant differences in
      gender, age and overall survival between patients with CBMI and DBMI, while the
      international prognostic index was significantly higher in patients with CBMI.
      CONCLUSION: Our study suggests that in patients with DLBCL with bone marrow
      involvement bone marrow FDG uptake depends on two types of infiltrate, comprising
      small (DBMI) or large (CBMI) cells. This may explain the apparent low sensitivity
      of FDG-PET previously reported for detecting bone marrow involvement.

PMID- 19096843
TI  - Mean and maximum standardized uptake values in [18F]FDG-PET for assessment of
      histopathological response in oesophageal squamous cell carcinoma or
      adenocarcinoma after radiochemotherapy.
AB  - PURPOSE: To evaluate the potential of [(18)F]fluorodeoxyglucose positron emission
      tomography (FDG-PET) for the assessment of histopathological response and
      survival after neoadjuvant radiochemotherapy in patients with oesophageal cancer.
      PATIENTS AND METHODS: In 2005 and 2006, 55 patients (43 men, 12 women; median age
      60 years) with locally advanced oesophageal cancer (cT3-4 Nx M0; 24 with squamous
      cell carcinoma, 31 with adenocarcinoma) underwent transthoracic en bloc
      oesophagectomy after completion of treatment with cisplatin, 5-fluorouracil, and
      radiotherapy ad 36 Gy in a prospective clinical trial. Of the 55 patients, 21
      (38%) were classified as histopathological responders (<10% vital residual tumour
      cells) and 34 (62%) as nonresponders. FDG-PET was performed before (PET 1) and 3
      4 weeks after the end (PET 2) of radiochemotherapy with assessment of maximum and
      average standardized uptake values (SUV) for correlation with histopathological
      response and survival. RESULTS: Histopathological responders had a slightly
      higher baseline SUV than nonresponders (p<0.0001 between PET 1 and PET 2 for
      responders and nonresponders) and the decrease was more prominent in responders.
      Except for SUVmax in patients with squamous cell carcinoma neither baseline nor
      preoperative SUV nor percent SUV reduction correlated significantly with
      histopathological response. Histopathological responders had a 2-year overall
      survival of 91 +/- 9% and nonresponders a survival of 53 +/- 10% (p = 0.007).
      CONCLUSION: Our study does not support recent reports that FDG-PET predicts
      histopathological response and survival in patients with locally advanced
      oesophageal cancer treated by neoadjuvant radiochemotherapy.

PMID- 19096845
TI  - Long-term efficacy of Helicobacter pylori eradication in patients with idiopathic
      thrombocytopenic purpura: 7-year follow-up prospective study.
AB  - Helicobacter pylori eradication is useful for improvement of a half of patients
      with idiopathic thrombocytopenic purpura (ITP), but its long-term therapeutic
      efficacy has not been elucidated. We investigated the long-term efficacy of H.
      pylori eradication in 30 cases with ITP that were included in our previous study
      regarding the association between H. pylori infection and ITP. Twenty-one cases
      were positive and nine cases were negative for H. pylori infection. H. pylori
      eradication therapy including secondary regimen was successful in 20 cases, half
      (responder) of whom showed ITP remission 1 month later. Nine responders could be
      followed up for a long time and did not show re-infection of H. pylori. Eight of
      nine needed no medication except for eradication therapy. Another case remained
      in remission for 1 year but thereafter needed a steroid therapy due to the
      recurrence. Eight nonresponders could be followed up for a long time. All these
      cases showed a bad clinical course even though they received the other post
      treatments including steroid therapy. Three of nine H. pylori-negative cases
      underwent eradication therapy after obtaining the written informed consent, but
      none of them showed improvement. Of these three cases, two cases could be
      followed up. Only one case remained a remission although receiving corticosteroid
      as a post-treatment. Conditions of H. pylori-negative ITP cases were usually
      unstable for a long time. H. pylori eradication has a short-term efficacy for
      about half of H. pylori-positive ITP patients, and the responders to the
      eradication therapy may receive a long-term clinical benefit without other
      therapies.

PMID- 19096844
TI  - Are "knife and fork" good enough for day case surgery of resistant tennis elbow?
AB  - This observational retrospective study was performed on 22 consecutive patients
      treated surgically in a day surgery unit for resistant tennis elbow to ascertain
      the effectiveness of the "knife and fork" procedure. All patients had an
      unfavourable response to nonsurgical treatment lasting at least six months. A
      simple and inexpensive "knife and fork" technique yielded excellent results in
      90.5% of patients and a high percentage (95.2%) of satisfied patients at an
      average follow-up of two years. There were no fair or poor results and no
      complications. We conclude that the "knife and fork" technique is a simple and
      dependable day case procedure. In the present National Health Service (NHS) era
      of tariff and "payment by results", this approach is more cost effective than an
      arthroscopic alternative.

PMID- 19096846
TI  - Hydroxyurea (HU) is effective in reducing JAK2V617F mutated clone size in the
      peripheral blood of essential thrombocythemia (ET) and polycythemia vera (PV)
      patients.
AB  - Ph-negative chronic myeloproliferative disorders (Ph(neg)cMPD) are treated
      according to the estimated vascular risk. The recent discovery of V617F point
      mutation of the JAK2 kinase, which frequently occurs in these diseases, has not
      changed their management so far. However, emerging data tend to support a
      prothrombotic role for the mutation, along with a better response of JAK2V617F
      mutated patients to hydroxyurea treatment. Our data further support this notion.

PMID- 19096847
TI  - Application of prolonged microdialysis sampling in carboplatin-treated cancer
      patients.
AB  - PURPOSE: To better understand the mechanisms underlying (in)sensitivity of tumors
      to anticancer drugs, assessing intra-tumor drug pharmacokinetics (PKs) could be
      important. We explored the feasibility of microdialysis in tumor tissue for
      multiple days in a clinical setting, using carboplatin as model drug. METHODS:
      Plasma and microdialysate samples from tumor and adipose normal tissues were
      collected up to 47 h after dosing in eight carboplatin-treated patients with an
      accessible (sub)cutaneous tumor. RESULTS: Pharmacokinetics were evaluable in
      tumor tissue in 6/8 patients and in adipose normal tissue in 3/8 patients.
      Concentration-time curves of unbound platinum in both the tissues followed the
      pattern of the curves in plasma, with exposure ratios of tissue versus plasma
      ranging from 0.64 to 1.46. CONCLUSIONS: Microdialysis can be successfully
      employed in ambulant patients for multiple days, which enables one to study
      tissue PK of anticancer drugs in normal and malignant tissues in more detail.

PMID- 19096848
TI  - Synergistic anti-tumor efficacy of lovastatin and protein kinase C-beta inhibitor
      in hepatocellular carcinoma.
AB  - PURPOSE: Hepatocellular carcinoma (HCC) is characterized by hypervascularity and
      chemoresistance. Protein kinase C (PKC) participates in cancer progression by
      enhancing anti-apoptotic signals, angiogenesis, and chemoresistance. Statins have
      a selective anti-cancer effect due to over-expression of 3-hydroxy-3
      methylglutaryl-coenzyme A reductase (HMG-CoAR) in cancer cells, but statins may
      also activate PKC. Thus, we hypothesized that simultaneous treatment with statin
      and PKC inhibitor might synergistically enhance their anti-tumor efficacies
      against HCCs. METHODS: Hepatocellular carcinoma cell growth was assessed using
      MTS assays, apoptotic cell death by DAPI staining, and apoptotic signaling
      cascades were explored by immunoblotting. An in vivo model of HCC was established
      in C3H mice intradermally implanted with MH134 cells. Lovastatin and/or a PKC
      inhibitor (enzastaurin) was subsequently administered. Anti-tumor efficacies were
      evaluated by measuring tumor volumes and quantifying apoptotic cells and
      microvessel densities (MVD). RESULTS: Co-treatment with lovastatin and
      enzastaurin was found to synergistically suppress HCC cell growth in vitro.
      Lovastatin induced HCC cellular apoptosis by activating mitochondrial apoptotic
      signals, and although enzastaurin alone did not induce apoptosis, its addition
      significantly enhanced lovastatin-induced apoptosis. This enhanced apoptosis was
      attributed to increased caspase-9 activation in these cells. Moreover, tumor
      growth was significantly suppressed in mice co-treated with lovastatin and
      enzastaurin, and percentages of TUNEL-positive cells were significantly increased
      and MVDs were significantly decreased in those mice. CONCLUSION: Combinatorial
      treatment with statin and PKC inhibitor was found to enhance anti-tumor efficacy
      in vivo and in vitro. Further studies are warranted to prove anti-tumor efficacy
      of this potential therapy in human HCCs.

PMID- 19096849
TI  - Distributed parameter identification for a label-structured cell population
      dynamics model using CFSE histogram time-series data.
AB  - In this work we address the problem of the robust identification of unknown
      parameters of a cell population dynamics model from experimental data on the
      kinetics of cells labelled with a fluorescence marker defining the division age
      of the cell. The model is formulated by a first order hyperbolic PDE for the
      distribution of cells with respect to the structure variable x (or z) being the
      intensity level (or the log(10)-transformed intensity level) of the marker. The
      parameters of the model are the rate functions of cell division, death, label
      decay and the label dilution factor. We develop a computational approach to the
      identification of the model parameters with a particular focus on the cell birth
      rate alpha(z) as a function of the marker intensity, assuming the other model
      parameters are scalars to be estimated. To solve the inverse problem numerically,
      we parameterize alpha(z) and apply a maximum likelihood approach. The
      parametrization is based on cubic Hermite splines defined on a coarse mesh with
      either equally spaced a priori fixed nodes or nodes to be determined in the
      parameter estimation procedure. Ill-posedness of the inverse problem is indicated
      by multiple minima. To treat the ill-posed problem, we apply Tikhonov
      regularization with the regularization parameter determined by the discrepancy
      principle. We show that the solution of the regularized parameter estimation
      problem is consistent with the data set with an accuracy within the noise level
      in the measurements.

PMID- 19096850
TI  - Comparing fibromyalgia patients from primary care and rheumatology settings:
      clinical and psychosocial features.
AB  - The aim of this study was to compare clinical symptoms, perceived health status,
      health resource use and psychosocial features in fibromyalgia (FM) patients at
      different health care levels. A total of 315 participants were recruited from
      primary care (PC) (n=101) and rheumatology settings (RS) (n=214). Subjects
      completed a protocol of clinical features and health resource use, hospital
      anxiety and depression scale, sickness impact profile, chronic pain self-efficacy
      scale, multidimensional pain locus of control scale, perceived health competence
      scale and chronic pain coping inventory. Student's t test, effect size, and
      contrast and power test were performed to examine differences between samples. FM
      patients treated in PC and RS were similar in most variables assessed and only
      differed significantly in tender points, sleep disturbance, wellness-focused
      coping strategies and in self-efficacy beliefs. The similarities do not support
      patient selection through care levels and thus, in the Spanish health care system
      at least, endorse PC as a reference unit for treatment and questioning the
      benefits of referring patients to RS.

PMID- 19096851
TI  - Preliminary study on the immunologic background of good clinical outcome in
      rheumatoid arthritis patients after one month therapy with leflunomide.
AB  - This preliminary study focuses on early peripheral cellular immune changes after
      1 month therapy with leflunomide, in 18 patients with severe rheumatoid
      arthritis, previously treated with methotrexate. A good clinical outcome of
      disease was documented and we showed that a particular target of short-time
      leflunomide therapy in rheumatoid arthritis was the peripheral innate immune
      system (NK cells and the population of granulocytes developing phagocytosis and
      superoxide anion production when challenged ex vivo with zymosan particles).
      Meanwhile, the high inter-individual variability of adaptive immunity required
      data analysis in subgroups of patients. We showed that the abnormal increase of
      peripheral leukocytes counts, or the decrease towards normal values of the
      CD4:CD8 lymphocytes ratio, or the inhibition of uridine uptake by ex vivo
      activated lymphocytes were consistent with a positive clinical evolution, proved
      by the reduction of tender/swollen joints, morning stiffness duration or acute
      phase response. We emphasized that significant benefits of short-term leflunomide
      therapy were associated with functional suppression of peripheral B lymphocytes.
      Hence, the positive evolution of rheumatoid arthritis patients seemed to be
      specifically linked to early drug-induced changes of trafficking or uridine
      metabolism of mononuclear cells.

PMID- 19096852
TI  - Characterization of a sugarcane (Saccharum spp.) gene homolog to the
      brassinosteroid insensitive1-associated receptor kinase 1 that is associated to
      sugar content.
AB  - The present article reports on the characterization of ScBAK1, a leucine-rich
      repeat receptor-like kinase from sugarcane (Saccharum spp.), expressed
      predominantly in bundle-sheath cells of the mature leaf and potentially involved
      in cellular signaling cascades mediated by high levels of sugar in this organ. In
      this report, it was shown that the ScBAK1 sequence was similar to the
      brassinosteroid insensitive1-associated receptor kinase1 (BAK1). The putative
      cytoplasmatic domain of ScBAK1 contains all the amino acids characteristic of
      protein kinases, and the extracellular domain contains five leucine-rich repeats
      and a putative leucine zipper. Transcripts of ScBAK1 were almost undetectable in
      sugarcane roots or in any other sink tissue, but accumulated abundantly in the
      mature leaves. The ScBAK1 expression was higher in the higher sugar content
      individuals from a population segregating for sugar content throughout the
      growing season. In situ hybridization in sugarcane leaves showed that the ScBAK1
      mRNA accumulated at much higher levels in bundle-sheath cells than in mesophyll
      cells. In addition, using biolistic bombardment of onion epidermal cells, it was
      shown that ScBAK1-GFP fusions were localized in the plasma membrane as predicted
      for a receptor kinase. All together, the present data indicate that ScBAK1 might
      be a receptor involved in the regulation of specific processes in bundle-sheath
      cells and in sucrose synthesis in mature sugarcane leaves.

PMID- 19096854
TI  - Is tubularization of the mobilized urethral plate a better alternative to
      tubularization of an incised urethral plate for hypospadias repair?
AB  - INTRODUCTION: Trial of a new procedure of hypospadias repair based on the
      incorporation of the entire available innate urethral tissue for the formation of
      neo-urethra in patients with hypospadias. MATERIALS AND METHODS: Fifteen
      consecutive children, nine with distal hypospadias and six with proximal
      hypospadias (all with severe chordee), whose parents consented to application of
      a new procedure of hypospadias repair, were the study subjects. This procedure is
      inspired by Cantwell Ransley procedure for epispadias repair and Snodgras
      procedure for hypospadias repair. The entire urethral plate was mobilized (i.e.,
      lifted off the corpora) distal to the urethral meatus and was tubularized in two
      layers; inner urethral skin and outer spongiosal tissue, in Duplay fashion. The
      repair was reinforced with dartos vascularized flap. The skin incisions on the
      urethral strip are guided by the disposition of the spongiosal tissue underlying
      the urethral plate (rather than the conventional U-shaped incision on either side
      of hypospadiac urethral meatus). In the patients with proximal hypospadias with
      severe chordee urethral advancement was combined to achieve orthoplasty and a
      single stage hypospadias repair. The catheter was removed on tenth postoperative
      day. RESULTS: Even in patients with proximal hypospadias with severe chordee,
      good single staged repair was achieved without resorting to dorsal plication that
      would have been necessary had any other methods based on the preservation of
      urethral plate was performed in these subjects. Therefore, the procedure was
      found to have an extended applicability to even those patients where tubularized
      incised urethral plate urethroplsty is not advised. All patients had good results
      (in 1 year follow-up), except in three early subjects of the series; two of whom
      developed minor urethrocutaneous fistulae (probably due to frank urinary leak
      secondary to repeated catheter blockade) and one developed partial glanular wound
      dehiscence. CONCLUSIONS: Though the authors have an initial limited experience
      with this procedure, the procedure is likely to have a promising future due to
      its versatility and utilization of the entire urethral tissue.

PMID- 19096853
TI  - Pistil-function breakdown in a new S-allele of European pear, S21*, confers self
      compatibility.
AB  - European pear exhibits RNase-based gametophytic self-incompatibility controlled
      by the polymorphic S-locus. S-allele diversity of cultivars has been extensively
      investigated; however, no mutant alleles conferring self-compatibility have been
      reported. In this study, two European pear cultivars, 'Abugo' and 'Ceremeno',
      were classified as self-compatible after fruit/seed setting and pollen tube
      growth examination. S-genotyping through S-PCR and sequencing identified a new S
      RNase allele in the two cultivars, with identical deduced amino acid sequence as
      S(21), but differing at the nucleotide level. Test-pollinations and analysis of
      descendants suggested that the new allele is a self-compatible pistil-mutated
      variant of S(21), so it was named S(21)*. S-genotypes assigned to 'Abugo' and
      'Ceremeno' were S(10)S(21)* and S(21)*S(25) respectively, of which S(25) is a new
      functional S-allele of European pear. Reciprocal crosses between cultivars
      bearing S(21) and S(21)* indicated that both alleles exhibit the same pollen
      function; however, cultivars bearing S(21)* had impaired pistil-S function as
      they failed to reject either S(21) or S (21)* pollen. RT-PCR analysis showed
      absence of S(21)* -RNase gene expression in styles of 'Abugo' and 'Ceremeno',
      suggesting a possible origin for S(21)* pistil dysfunction. Two polymorphisms
      found within the S-RNase genomic region (a retrotransposon insertion within the
      intron of S(21)* and indels at the 3'UTR) might explain the different pattern of
      expression between S(21) and S(21)*. Evaluation of cultivars with unknown S
      genotype identified another cultivar 'Azucar Verde' bearing S(21)*, and pollen
      tube growth examination confirmed self-compatibility for this cultivar as well.
      This is the first report of a mutated S-allele conferring self-compatibility in
      European pear.

PMID- 19096855
TI  - Hepatectomy for liver metastasis of colorectal cancer.
AB  - OBJECTIVE: The objective of this study was to investigate whether hepatic
      resection (HR) can increase the survival of liver metastasis of colorectal cancer
      (CRC). MATERIALS AND METHODS: CRC patients (n=669) with liver metastasis treated
      at the Zhongshan Hospital, Fudan University from 1/2000 to 7/2007 were included
      in the study to investigate the relationship between HR and cancer survival.
      RESULTS: CRC patients (n=669) with liver metastases who had primary tumor
      resection were grouped in synchronous liver metastasis (SLM; 56.7%, n=379) and
      metachronous liver metastasis (MLM) groups (43.3%, n=290). Hepatic resection
      rates were lower (32.5%, n=123) in the SLM than the MLM group (44.8%, n=130,
      P<0.05). The 30-day mortality rate in the MLM (2.3%) was significantly lower than
      SLM (2.4%) groups. The 5-year survival rates (36.6%) was same compared to SLM
      group (33.1%, P>0.05). One-, 2-, and 3-year survival of stages I and II operation
      cases were 92.5% vs 86.5%, 0.7% vs 58.0%, and 42.1% vs 44.9% (P>0.05) in the SLM
      group, respectively. Recurrence after first hepatic resection associated with a
      2.23-fold increased risk of death (P<0.01). Incision margins larger than 1 cm and
      HR for recurrence associated with 34% and 27% (P<0.05) decreased death risk.
      CONCLUSIONS: Hepatic resection could help the survival of liver metastasis of
      colorectal cancer, and stage I surgery is safe for this disease.

PMID- 19096856
TI  - [Vasculitis. Treatment outcome parameters].
AB  - The definition of outcome parameters has improved the care of vasculitis patients
      dramatically in recent decades. In the first phase of joint European studies,
      disease stages and activity were defined. In the second and third phases results
      of the randomized and controlled trials were summarized and published as European
      recommendations for the care of small and large vessel vasculitis. Irrespective
      of the type of vasculitis, inducing remission, maintaining remission and
      preventing disease- and therapy-related complications are the main outcome
      criteria.

PMID- 19096857
TI  - Correction of severe wrist deformity following physeal arrest of the distal
      radius with the aid of a three-dimensional computer simulation.
AB  - Growth arrest following physeal injury may result in severe limb deformity. We
      report a case of complex wrist deformity caused by injury to the distal radial
      physis resulting in radial shortening and abnormal inclination of the radial
      articular surface, which was successfully treated by gradual correction after
      computer simulation. The simulation enabled us to develop an appropriate
      operative plan by accurately calculating the axis of the three-dimensional (3D)
      deformity using computer bone models. In the simulative surgery with a full-size
      stereolithography bone model, an Ilizarov external fixator was applied to the
      radius such that its two hinges were located on the virtual axis of the
      deformity, which was reproduced in the actual surgery. This technique of 3D
      computer simulation is a useful alternative to plan accurate correction of
      complex limb deformities following growth arrest.

PMID- 19096859
TI  - A unique case of ovarian psammocarcinoma with mediastinal, pulmonary,
      subcutaneous, and omental metastases.
AB  - Psammocarcinoma is a rare form of serous ovarian and peritoneal carcinoma,
      characterized by abundant psammoma bodies, invasiveness, and low-grade
      cytological features. Many of the cases which have been reported had extraovarian
      spread and peritoneal seeding at the time of presentation. We present a case of
      45-year-old woman with ovarian psammocarcinoma who initially presented with a
      metastatic subcutaneous nodule, and was found to have pulmonary and mediastinal
      metastases. We believe this to be the first report of a psammocarcinoma with
      these metastases. Ovarian and peritoneal psammocarcinomas are quite rare, and
      because of this, knowledge of their behavior is limited. Although most seem to
      follow an indolent course similar to that of borderline lesions of the ovary,
      this case demonstrates that some of these tumors may be clinically aggressive
      with distant metastases.

PMID- 19096858
TI  - Microwave endometrial ablation as an alternative to hysterectomy for the emergent
      control of uterine bleeding in patients who are poor surgical candidates.
AB  - BACKGROUND: Microwave endometrial ablation is a new, minimally invasive treatment
      option for menorrhagia. Its popularity in many countries is increasing due to its
      safety and simplicity. CASES: We treated menorrhagia due to submucosal myomas in
      two patients with a modified microwave endometrial ablation device. Surgery was
      contraindicated in the first patient secondary to medical co-morbidities and in
      the second patient because of acute hemorrhagic shock. In both cases, the
      operation was highly effective and each patient was satisfied with her treatment
      outcome. CONCLUSION: Given its safety, simplicity, and effectiveness, microwave
      endometrial ablation may be widely adopted for the emergent control of uterine
      bleeding in patients with poor surgical candidates.

PMID- 19096860
TI  - Ovarian embedding of a transmigrated intrauterine device: a case report and
      literature review.
AB  - AIM: To report an unusual location of a transmigrated IUD which become embedded
      in the right ovary causing chronic pelvic pain and dyspareunia. CASE: A 22-year
      old woman who had an IUD (Copper T), inserted 7 years ago presented with
      complaint of lower abdominal pain. Pelvic ultrasonographic examination revealed
      ovarian embedding of the IUD. Laparoscopic IUD removal was successfully
      performed. DISCUSSION: De novo lower abdominal pain in a woman with an IUD in
      situ should alert the clinician to the possibility of total or partial
      transmigration of the device into the pelvis or abdomen. Ovarian penetration is
      very rare and this is the second case of IUD transmigration into the ovary
      reported in the medical literature.

PMID- 19096861
TI  - Prognosticators and the role of lymphadenectomy in uterine leiomyosarcomas.
AB  - OBJECTIVE: To analyze prognostic factors, the role of lymphadenectomy and
      postoperative adjuvant treatments in patients with uterine leiomyosarcomas (LMS).
      STUDY DESIGN: Sixty-three patients with uterine LMS are retrospectively analyzed
      with respect to both DFS and OS. RESULTS: Multivariate DFS analysis revealed
      percentage necrosis to be the unique factor to be significant (median DFS was
      3.31 years for <25% necrosis and 0.78 for >25% necrosis). Multivariate analysis
      revealed the mitotic counts to be the unique significant factor affecting the OS
      (median OS was 7.20 and 1.73 years, respectively, for patients with mitotic
      counts of 1-5 and >6; respectively). Median DFS was 2.51 years for patients who
      had undergone lymphadenectomy and 2.36 years for remaining who did not have a
      lymphadenectomy procedure (P = 0.4). With respect to OS, median values were 2.44
      and 3.16 years, respectively (P = 0.7). Number of the resected lymph nodes was
      also not significant for both OS and DFS. CONCLUSIONS: Mitotic counts and
      percentage necrosis have significant effects on OS and DFS; respectively. Neither
      the performance nor the extent of lymphadenectomy has an effect on patient
      survival.

PMID- 19096862
TI  - Rhinitis medicamentosa: what an otolaryngologist needs to know.
AB  - Rhinitis medicamentosa (RM) is a drug induced non-allergic rhinitis associated
      with prolonged use of topical nasal decongestants. This review discusses the
      nasal mucosa microcirculation, basic pharmacology of topical decongestants and
      the theories of the pathophysiology of RM. Diagnostic problems are discussed in
      addition to the current opinion on how to treat RM.

PMID- 19096863
TI  - Critical literature review on the management of intraparotid facial nerve
      schwannoma and proposed decision-making algorithm.
AB  - Management of intraparotid facial nerve schwannomas (IFNS) is very challenging
      because the diagnosis is often made intra-operatively and in most cases,
      resection could lead to severe facial nerve (FN) paralysis, with important
      aesthetic consequences. Articles in the English language focused on the
      management of FN schwannoma have been selected and critically reviewed. A
      decision-making algorithm is proposed. In the case of type A or B neoplasms, or
      in case of a pre-operative FN House-Brackmann (HB) grade IV or worse, the authors
      would favor a resection of the IFNS and (where necessary) a reconstruction of the
      nerve. In the case of pre-operative HB grade III or better and type C or D
      neoplasms, patients would undergo an intra-operative biopsy to rule out
      malignancy, and a possible conservative management could be adopted. Localization
      and adherences of IFNS, as well as pre-operative FN function are important
      factors that must be considered in the decision-making process for IFNS to
      optimize the functional outcomes.

PMID- 19096864
TI  - Importance of patient, tumour and treatment related factors on quality of life in
      head and neck cancer patients after definitive treatment.
AB  - The purpose of this study is to assess patient, tumour and treatment related
      factors on quality of life (QoL) outcomes of patients who received definitive or
      postoperative radiotherapy +/- chemotherapy for head and neck (H&N) cancer. In
      this cross-sectional study, 110 H&N cancer patients were evaluated in follow-up
      visit and were asked to fill out the European Organisation for Research and
      Treatment of Cancer QoL Core Questionnaire (QLQ-C-30) and H&N Module (QLQ-H&N35).
      Patients were also graded for their late side effects using EORTC/RTOG scoring
      system. The QLQ C-30 and QLQ-H&N35 mean scores were compared using ANOVA analysis
      for these variables: age, gender, occupation, educational status, social security
      status, place of residence, tumour localization, clinical stage, comorbidity,
      Karnofsky performance score, treatment modality and side effects. Median follow
      up was 29 (4-155) months. Tumour localization was significant factor affecting
      physical (P = 0.03), social (P = 0.01), cognitive (P = 0.002) functioning.
      Treatment modality had significant impact on the physical (P = 0.02) and
      cognitive scores (P = 0.008). Global QoL was affected significantly by disease
      stage (P = 0.01) and occupation (P = 0.01). The QLQ-H&N35 scores were found
      significantly higher in patients with moderate/severe late morbidity. Tumour
      localization and the treatment modality are the most important factors affecting
      the QoL of H&N cancer patients treated definitively.

PMID- 19096865
TI  - Pupil campimetry in patients with retinitis pigmentosa and functional visual
      field loss.
AB  - BACKGROUND: The aim of our study was to test in a small series of cases if pupil
      perimetry can prove real concentric visual field loss in retinal degeneration and
      distinguish from feigned visual field loss. METHODS: By means of infrared-video
      pupillography, light responses to perimetric stimuli were recorded. The stimulus
      pattern consisted of 41 stimuli presented in the central 30 degrees visual field.
      Stimulus intensity was 140 cd/m(2). 5 healthy subjects, 6 patients with retinitis
      pigmentosa and 2 patients with suspected functional visual field loss were
      examined. RESULTS: Pupil perimetry was able to reproduce the visual field in
      retinitis pigmentosa very well. Normal subjects and patients with suspected
      feigned visual field loss showed normal pupillomotor fields, different from the
      findings in retinitis pigmentosa. CONCLUSIONS: This study provides sufficient
      evidence that pupil campimetry is applicable for differentiating between retinal
      dystrophy and functional concentric visual field loss. Possible residual light
      sensitivity of the blind retina due to melanopsin ganglion cells is obviously not
      sufficient to provide a pupillary light response to perimetric stimuli.

PMID- 19096866
TI  - DEHP effects on histology and cell proliferation in lung of newborn rats.
AB  - Di-(2-ethylhexyl)-phthalate (DEHP), the plasticizer employed in the fabrication
      of polyvinyl chloride, is known to be released by many medical devices, namely
      endotracheal tubes currently utilised for pulmonary ventilation of pre-term
      newborns. When experimentally administered, especially to rodents, the phthalate
      reportedly causes alterations to several tissues, immature animals being even
      more responsive targets than adult ones. In the present research, female rats
      were fed with DEHP in the last week of pregnancy and after delivery, and lung of
      their pups was morphologically and immunohistochemically analysed. We detected
      significant alveolar simplification (larger but fewer alveoli with decreased
      septation), with consequent sensible reduction of gas-exchange surface, at
      several stages of postnatal development, in distal lung parenchyma of DEHP
      treated rats. Moreover, the quantification of PCNA-expressing cells demonstrates
      that in treated pups the proliferation rates of epithelial and mesenchymal cells
      progressively increased during the first two postnatal weeks, at difference with
      controls animals, where the highest proliferation levels were reached at
      postnatal day 7. The obtained results strongly support the hypothesis that DEHP
      profoundly affects the alveolarization process in mammalian lung.

PMID- 19096868
TI  - Relative importance of lean and fat mass on bone mineral density in a group of
      adolescent girls and boys.
AB  - The aim of this study was to determine the relative importance of lean mass (LM)
      and fat mass (FM) on bone mineral density (BMD) in a group of adolescent girls
      and boys. A total of 65 adolescent boys and 35 adolescent girls participated in
      this study. Whole body (WB) and lumbar spine (L1-L4) BMD were measured by dual
      energy X-ray absorptiometry (DXA). Body composition was assessed using the same
      technique. In boys, LM was strongly related to WBBMD (r = 0.68; p < 0.001) and to
      L1-L4 BMD (r = 0.61; p < 0.001), whereas FM was not positively related to BMD and
      was negatively associated with WB bone mineral apparent density (WBBMAD). In
      girls, both LM and FM were positively related to WBBMD (r = 0.41; p < 0.05 and r
      = 0.49; p < 0.01, respectively), whereas only FM was correlated to L1-L4 BMD (r =
      0.33; p < 0.05). Finally, in a multiple regression analysis, FM was found to be a
      better positive determinant of WBBMD than LM in girls, whereas in boys, FM was
      found to be a negative determinant of WBBMD and L1-L4 BMD. This study suggests
      that LM is a strong determinant of WBBMD and L1-L4 BMD in boys, and that FM is a
      stronger determinant of WBBMD than LM in girls.

PMID- 19096869
TI  - Cold-induced vasodilation.

PMID- 19096867
TI  - Preserved expression of fibroblast growth factor (FGF)-2 and FGF receptor 1 in
      brain and spinal cord of amyotrophic lateral sclerosis patients.
AB  - Impaired trophic support of motor neurons appears to be an important pathogenic
      factor in amyotrophic lateral sclerosis (ALS). We investigated the mRNA
      expression of the pluripotent fibroblast growth factor 2 (FGF-2) and its
      receptors in post mortem spinal cord of ALS and control patients. FGF-2 and FGF
      receptor (FGFR) 1 and 2 transcripts were first studied in the spinal cord using
      RT-PCR. The cellular distribution of FGF-2 and FGFR mRNA in the spinal cord,
      motor cortex and brain stem was then assessed by in situ hybridization
      histochemistry. RT-PCR revealed the presence of FGF-2 and FGF receptor 1 and 2
      transcripts with no obvious differences between ALS and control spinal cord.
      Comparing mRNA expression in the motoneuron-containing ventral horn with the
      clinically and neuropathologically spared dorsal horn of ALS spinal cord
      displayed similar expression levels. At the cellular level, we found a prominent
      neuronal expression of FGF-2 and FGFR1. Interestingly, both morphologically
      intact and damaged motoneurons showed positive staining for FGF-2 and FGFR1
      transcripts. The distribution of cells expressing FGF-2 and FGFR1 transcripts
      showed no differences between ALS and controls. Our data suggest that FGF-2 and
      FGFR1 expression is preserved in the motor system in end stage ALS.

PMID- 19096870
TI  - The eccentric muscle loading influences the pacing strategies during repeated
      downhill sprint intervals.
AB  - The purpose was to compare self-chosen pace during ten repetitions of 60 m
      running sprints performed on a level surface (SPL), or when running uphill (SPU)
      or downhill (SPD) on a 4.7% slope. When expressed as percent of maximal running
      speed for corresponding condition, SPD was lower than SPL (95.28 +/- 1.93 vs.
      97.31 +/- 1.29%; P = 0.044), which was lower than SPU (97.31 +/- 1.29 vs. 98.09
      +/- 0.74%; P = 0.026). Heart rates, blood lactate concentrations and general
      perceived exertion were lower during SPD (163.8 +/- 8.3 bpm, 11.66 +/- 1.24 mmol
      L( -1), and 4.1 +/- 1.0) than SPL (169.8 +/- 7.8 bpm, 13.69 +/- 0.33 mmol L(-1),
      and 5.8 +/- 0.6), which were lower than SPU (174.9 +/- 8.7 bpm, 15.27 +/- 0.02,
      mmol L(-1), and 6.3 +/- 0.5) (P < 0.05 for all analyzes). Results show that the
      level of eccentric muscle loading influences the pacing strategy.

PMID- 19096871
TI  - The dynamic surface of dividing cyanelles and ultrastructure of the region
      directly below the surface in Cyanophora paradoxa.
AB  - The cyanelles of glaucocystophytes are probably the most primitive of known
      extant plastids and the closest to cyanobacteria. Their kidney shape and FtsZ arc
      during the early stage of division define cyanelle division. In order to deepen
      and expand earlier results (Planta 227:177-187, 2007), cells of Cyanophora
      paradoxa were fixed with two different chemical and two different freeze-fixation
      methods. In addition, cyanelles from C. paradoxa were isolated to observe the
      surface structure of dividing cyanelles using field emission scanning electron
      microscopy (FE-SEM). A shallow furrow started on one side of the division plane.
      The furrow subsequently extended, covering the entire division circle, and then
      invaginated deeply, becoming clearly visible. The typical FtsZ arc was 2.3-3.4
      microm long. This length matches that of the cleavage furrow observed using FE
      SEM. The cyanelle cleavage furrows are from one-fourth to one-half of the
      circumference of the division plane. The shallow furrow that appears on the
      cyanelle outer surface effectively changes the division plane. Using freeze
      fixation methods, the electron-dense stroma and peptidoglycan could be
      distinguished. In addition, an electron-dense belt structure (the cyanelle ring)
      was observed inside the leading edge at the cyanelle division plane. The FtsZ arc
      is located at the division plane ahead of the cyanelle ring. Immunogold-TEM
      localization shows that FtsZ is located interiorly of the cyanelle ring. The lack
      of an outer PD ring, together with the arch-shaped furrow, suggests that the
      mechanical force of the initial (arch shaped) septum furrow constriction comes
      from inside the cyanelle.

PMID- 19096872
TI  - Biomaterial-induced sarcomagenesis is not associated with microsatellite
      instability.
AB  - Sarcomagenesis, in contrast to carcinogenesis, is poorly understood.
      Microsatellite instability has been implicated in the development of many
      cancers, in particular those associated with chronic inflammatory conditions. In
      an experimental animal model, rats developed not only a peri-implantational
      chronic inflammatory reaction, but also malignant mesenchymal tumors in response
      to different biomaterials. Therefore, it was the aim of our study to test if the
      development of biomaterial-induced sarcomas is characterized by a mutator
      phenotype. A multiplex-PCR approach was designed to screen biomaterial-induced
      sarcomas for the presence of microsatellite instability. Seven different
      microsatellite loci were tested in ten tumors for microsatellite instability
      using a fluorochrome-labelled multiplex-PCR and subsequent fragment analysis. All
      tumors provided a microsatellite-stable phenotype at all loci tested. Our data
      suggest that microsatellite instability is rarely or not at all a feature of
      malignant transformation of biomaterial-induced soft tissue tumors. Thus, there
      is no evidence that a mutator phenotype is a hallmark of biomaterial-induced
      sarcomagenesis.

PMID- 19096873
TI  - Tetracycline-resistant Escherichia coli strains are inherited from parents and
      persist in the infant's intestines in the absence of selective pressure.
AB  - The study investigated tetracycline (TC), ampicillin (AMP), cefazolin (CEF), and
      trimethoprim (TMP) resistance in Escherichia coli (E. coli) in the feces of 21
      infants up to 6 months of age and in their parents in the absence of selective
      antimicrobial pressure. Clonality of strains was assessed by pulsed-field gel
      electrophoresis. Three infants had resistant E. coli strains in their feces
      identical to the mothers' from week 1 on, which persisted over weeks. From week 2
      on, in another four infants, persisting resistant E. coli were found, two of them
      identical to the mothers'. All of these persisting E. coli strains (except one
      family) showed at least resistance to TC. In infants, resistant E. coli strains
      inherited from their mothers tended to persist over months. Therefore, the
      persistence of resistant E. coli and their possible capacity to cause symptomatic
      infection or transfer its resistance genes to other bacteria deserves more
      attention.

PMID- 19096874
TI  - Estimated intake levels of methylmercury in children, childbearing age and
      pregnant women in a Mediterranean region, Murcia, Spain.
AB  - Methylmercury (MeHg) is a bioaccumulable toxin in the trophic chain and a
      powerful neurotoxin during fetal and child development. Consumption of
      contaminated fish and shellfish is a principal environmental source of MeHg
      exposure. This study was designed to assess the Hg and estimated MeHg intake in
      vulnerable groups of the Murcia region, a Mediterranean part of Spain, compared
      with international regulations. A validated food frequency questionnaire was used
      to assess seafood consumptions in 320 children younger than 10 years, 301 women
      of childbearing age, and 537 pregnant women. Hg concentrations were measured in
      the most consumed fish products by cold vapor generation-atomic fluorescence
      spectrometry. The weekly intake of MeHg (microg/kg bw/week) was 2.60 (95% CI =
      2.10-3.10) in children 1-5 years, 2.65 (95% CI = 2.26-3.03) in children 6-10
      years, 0.98 (95% CI = 0.89-1.07) in women of childbearing age, and 0.88 (95% CI =
      0.81-0.95) in pregnant women. The main exposure to MeHg, especially in young
      children, is related to intake of bluefin tuna and swordfish. Fifty-four percent
      of children aged 1-10 years, 10% of pregnant women, and 15% of women of
      childbearing age exceed the Joint Expert Committee on Food Additives provisional
      tolerable weekly intake of MeHg. In the Murcia region, where fish is a central
      component of the diet, the focus should be on educating vulnerable populations to
      reorient fish consumption in order to lower the amount of Hg incorporated with
      the diet as well as to reduce Hg emissions into the environment.

PMID- 19096875
TI  - Extrauterine growth retardation in premature infants in Shanghai: a multicenter
      retrospective review.
AB  - Intrauterine growth retardation (IUGR) represents the degree of body growth and
      development decided by genes and by placental function. Extrauterine growth
      retardation/restriction (EUGR) refers to severe nutritional deficits during the
      first weeks of life that result in growth that is less than expected based on
      intrauterine growth rates (growth values < or =10th percentile of intrauterine
      growth expected in accordance with the estimated gestational age). The deficits
      affect not only weight but also head circumference and height. As is well known,
      a nutrition support team (NST) is a multidisciplinary team comprised of
      physicians, nurses, dietitians, pharmacists, social workers, and medical
      technologists who provide nutritional management. In this study, we review 2,015
      premature infants (1,209 boys and 806 girls) from four hospitals in the Shanghai
      area from January 1, 2003 to December 31, 2006, two of which had NSTs. The
      overall incidence of EUGR was 56.8% assessed by weight, while the incidence of
      IUGR was 26.1%. Higher incidence of EUGR was associated with lower birth weight,
      but higher gestational age. There was a significant relationship between EUGR
      incidence and NST availability (chi(2) = 60.630, p < 0.001), though there was no
      similar finding for IUGR incidence. The incidence of EUGR was 44% in NST
      hospitals and 62.6% in non-NST hospitals. According to logistic regression, the
      following five factors were related to EUGR: male gender, gestational age at
      birth, birth weight, length of hospital stay, and NST availability. NSTs reduced
      the risk of EUGR by a magnitude of 0.47. EUGR remains a serious problem in
      premature infants in Shanghai, but NSTs can reduce EUGR incidence.

PMID- 19096876
TI  - Saccharomyces boulardii in childhood.
AB  - INTRODUCTION: Probiotics are live microorganisms which confer a health benefit on
      the host. Saccharomyces boulardii, a yeast, has been found to be an effective
      probiotic in double-blind placebo-controlled randomized clinical studies.
      MATERIALS AND METHODS: We reviewed the established mechanisms of actions and
      clinical efficacy in children of S. boulardii. CONCLUSIONS: The mechanisms of
      action of S. boulardii depend mainly on the inhibition of some bacterial toxins,
      anti-inflammatory effects, and on stimulating effects on the intestinal mucosa
      such as trophic effects on the brush border enzymes and immunostimulatory
      effects. At present, in pediatric populations, there is evidence that S.
      boulardii is beneficial for the treatment of acute gastroenteritis and the
      prevention of antibiotic-associated diarrhea. More data are needed in other
      indications such as traveller's diarrhea, Helicobacter pylori eradication, and
      inflammatory bowel disease. S. boulardii is a yeast strain that has been
      extensively studied in vitro and in vivo. Recent data have opened the door for
      new therapeutic indications.

PMID- 19096878
TI  - Multiplex PCR on single unembryonated Ascaris (roundworm) eggs.
AB  - A sensitive and inexpensive method for DNA isolation and amplification by
      polymerase chain reaction (PCR) from single unembryonated Ascaris sp. eggs is
      described. The resistant shell of single eggs was crushed mechanically and PCR
      applied to the crude egg contents without any further purification steps. The
      ITS1 region of the rDNA and three regions of the mtDNA could be successfully
      amplified. Using two primer sets, it was possible to amplify the rDNA and mtDNA
      simultaneously in one single reaction. The ability to perform PCR on single
      unembryonated eggs may result in better and more precise species identification
      of eggs recovered from faecal material, environmental samples and possibly
      archaeological samples. In addition, single egg PCR makes it possible to perform
      population genetic studies without having to recover adult worms by deworming or
      autopsy.

PMID- 19096877
TI  - In vitro schistosomicidal activity of curcumin against Schistosoma mansoni adult
      worms.
AB  - The in vitro schistosomicidal activity of curcumin (doses ranging from 5 to 100
      microM) was carried out against Schistosoma mansoni adult worms. Curcumin (at 50
      and 100 microM) caused death of all worms. When tested at the doses of 5 and 20
      microM, it decreased the worm viability in comparison with negative (Roswell
      Memorial Park Institute (RPMI) 1640 medium alone or RPMI 1640 medium with 10%
      dimethyl sulfoxide) and positive (heat-killed worms at 56 degrees C or
      praziquantel 10 microM) control groups. All pairs of coupled adult worms were
      separated into individual male and female by the action of curcumin at the doses
      of 20 to 100 microM. When tested at 5 and 10 microM, curcumin reduced egg
      production by 50% in comparison with the positive control group. It is the first
      time that the schistosomicidal activity has been reported for curcumin.

PMID- 19096879
TI  - Outcome of severe acute post-streptococcal glomerulonephritis in New Zealand
      children.
AB  - Post-streptococcal glomerulonephritis (PSGN) is the commonest cause of severe
      acute glomerulonephritis in New Zealand children, with the majority (85%) of the
      patients being of either Pacific Island or Maori ethnicity. We have performed a
      retrospective study on 27 pediatric patients with acute PSGN. Of these patients,
      those with crescentic glomerulonephritis (n = 11) had a greater tendency (72.7%)
      for needing acute dialysis and were left with persistent urinary sediment
      abnormalities after a mean follow-up of 3.2 years (95% confidence interval 2.1
      4.3). The efficacy of immunosuppression in the group with crescentic disease was
      uncertain. The severity of renal histopathological abnormalities as judged by the
      total biopsy score did not correlate with either presentation or eventual
      outcome. Severe childhood acute post-streptococcal glomerulonephritis, although
      uncommon, results in significant long-term renal morbidity, particularly among
      Maori and Pacific Island children.

PMID- 19096880
TI  - Chronic peritoneal dialysis in a 4-year-old boy with Lesch-Nyhan disease.

PMID- 19096881
TI  - Blood pressure load, proteinuria and renal function in pre-hypertensive children.
AB  - It is as yet unclear whether blood pressure load (BPL) can affect renal function
      in pre-hypertensive children. We have studied 250 children, with a mean age of
      9.12 +/- 3.28 years, with the aim of assessing if pre-hypertension in children
      can indeed affect renal function. The study cohort consisted of 146 children with
      pre-hypertension (group P) and a control group of 104 children with normal blood
      pressure (group C). All children were tested for orthostatic proteinuria, an
      exclusion criterion, glomerular filtration rate (GFR), and proteinuria, and
      ambulatory blood pressure monitoring was performed. Based on the BPL, group P was
      further subdivided into group P1 (BPL <or= 40%, low BPL) and group P2 (BPL > 40%,
      high BPL). We found that GFR was reduced in pre-hypertensive children (90.74 +/-
      48.69 vs. 110.32 +/- 20.30 ml/min per 1.73 m(2), p < 0.0001) and that proteinuria
      was increased (145.36 +/- 110.91 vs. 66.84 +/- 42.94 mg/m(2) per 24 h; p <
      0.0001). However, mean values were still within normal limits. A comparison of
      the group with high BPL and that with low BPL revealed that the former had
      relatively reduced GFR (79.15 +/- 42.04 vs. 96.78 +/- 51.20 ml/min per 1.73 m(2);
      p < 0.006) and increased proteinuria (198.29 +/- 142.17 vs. 118.31 +/- 80.07
      mg/m(2) per 24 h; p < 0.036). In comparison to the reference values of the normal
      population, the GFR was reduced and proteinuria was increased in the group with
      high BPL. Based on our results, pre-hypertension in children with high BPL seems
      to be associated with reduced GFR and increased proteinuria. A reasonable doubt
      remains that the patients with higher proteinuria and larger reduction of GFR may
      harbor an as yet unknown subclinical renal condition responsible for the onset of
      pre-hypertension. Therefore, children with even mildly elevated BP are at risk of
      developing renal damage and should change their lifestyle to prevent further
      increases in BP.

PMID- 19096882
TI  - Quality management of potential chemotherapy-induced neutropenic complications:
      evaluation of practice in an academic medical center.
AB  - GOALS: Management of the risk of potential chemotherapy-induced neutropenic
      complications such as febrile neutropenia (FN) and severe neutropenia (SN) is a
      quality of care priority. How frequently does care at our institution conform to
      established guidelines? MATERIALS AND METHODS: This retrospective chart review
      study included a random sample of 305 cancer patients receiving care at a single
      US academic medical center. Abstracted data included demographics, risk factors,
      and outcome variables (e.g., development of FN/SN, administration of myeloid
      growth factors). To evaluate quality of care, we assessed conformance between
      actual practice and established clinical practice guidelines for the use of
      myeloid growth factors from the National Comprehensive Cancer Network (NCCN).
      MAIN RESULTS: Of the 305 cases reviewed, 8% were classified as low risk (<10%),
      48% as intermediate risk (10-20%), and 44% as high risk (>20%), using the risk
      classifications in the NCCN guidelines modified to accommodate illness and other
      risk factors. Thirty-four percent received prophylactic administration of myeloid
      growth factors. Half of the cases had adequate documentation of mid-cycle
      absolute neutrophil count to determine whether FN/SN developed. Among these cases
      with adequate documentation, 21% developed FN/SN. Use of growth factors did not
      conform to established quality guidelines. Overall, 77 of 133 (58%) high-risk
      cases received myeloid growth factors, whereas six of 25 (24%) low-risk cases
      received myeloid growth factors. CONCLUSIONS: Routine clinical practice in this
      academic oncology setting was poorly aligned with established guidelines; there
      is substantial opportunity to standardize clinical strategies and increase
      conformance with evidence-based guidelines.

PMID- 19096883
TI  - Infective and thrombotic complications of central venous catheters in patients
      with hematological malignancy: prospective evaluation of nontunneled devices.
AB  - GOALS: Central venous catheter (CVC)-related bloodstream infection (CR-BSI) is a
      significant complication in hematology patients. A range of CVC devices may be
      used, and risks for the development of complications are not uniform. The
      objectives of this study were to determine the natural history and rate of CVC
      related complications and risk factors for CR-BSI and to compare device-specific
      complications in a hematology population. PATIENTS AND METHODS: An observational
      cohort of patients with hematologic malignancy was prospectively studied
      following CVC insertion. Participants were reviewed until a CVC-related
      complication necessitated device removal, completion of therapy, death, or
      defined end-of-study date. The National Nosocomial Infection Surveillance
      definition for CR-BSI was used. Overall and device-specific rates of infective
      and noninfective complications were calculated and potential risk factors were
      captured. MAIN RESULTS: One hundred six CVCs (75 peripherally inserted central
      venous catheters [PICCs], 31 nontunneled CVCs) were evaluated in 66 patients,
      over 2,399 CVC days. Thrombosis occurred in 16 cases (15.1%), exit-site infection
      in two (1.9%), and CR-BSI in 18 (7.5 per 1,000 CVC days). No significant
      differences were found when complication rates in PICC and nontunneled devices
      were compared. An underlying diagnosis of acute myeloid leukemia was negatively
      associated with CR-BSI (odds ratio (OR) 0.14, p = 0.046), and a previous
      diagnosis of fungal infection was associated with infection (OR 22.82, p =
      0.031). CONCLUSIONS: CR-BSI rates in our hematology population are comparable to
      prior reports. A low rate of exit-site infection and high proportion of
      thrombotic complications were observed. No significant differences in thrombotic
      or infective complications were evident when PICC and nontunneled devices were
      compared. PICC devices are a practical and safe option for management of
      hematology patients.

PMID- 19096884
TI  - Three-dimensional analysis of cervical spine motion: reliability of a computer
      assisted magnetic tracking device compared to inclinometer.
AB  - We aimed to investigate the reliability and reproducibility of a magnetic
      tracking technique for the assessment of overall cervical spine motion (principal
      and coupled movements). Ten asymptomatic male volunteers with a mean age of 29.3
      years (range 20-37 years) were included in the study. Flexion, extension, left
      and right lateral bending and left and right axial rotation were measured using a
      magnetic tracking device (MTD) mounted onto a custom head-piece. For rotational
      movements in the frontal and sagittal planes the results were compared with the
      measurements of two standard inclinometers. Intra-observer, inter-observer and
      intra-instrument reliability was assessed with the intraclass correlation
      coefficient method. There were no significant differences for all motion
      measurements between the MTD and the inclinometer. High inter-observer
      reliability was found in flexion, extension, axial rotation and lateral bending
      indicating that the testing routine is applicable for different examiners. The
      intra-observer variability was high in flexion and extension, whereas in lateral
      bending the reliability coefficients were lower and displayed a fair to good
      reliability for most of the measurements with the MTD. The results of the MTD
      were found to be highly comparable with the inclinometer results with an inter
      instrument correlation coefficient ranging from 0.88 to 0.99. The MTD is a
      reliable, reproducible method for three-dimensional motion analysis of the
      cervical spine and therefore a valuable method both for the clinical assessment
      of various degenerative and traumatic disorders and as a supplement of different
      therapeutic procedures and rehabilitation.

PMID- 19096885
TI  - Conformational and electronic (AIM/NBO) study of unsubstituted A-type dimeric
      proanthocyanidin.
AB  - The conformational space of the unsubstituted A-type dimeric proanthocyanidin was
      scanned using molecular dynamics at a semiempirical level, and complemented with
      functional density calculations. The lowest energy conformers were obtained.
      Electronic distributions were analysed at a higher calculation level, thus
      improving the basis set. A topological study based on Bader's theory ( AIM: atoms
      in molecules) and natural bond orbital (NBO) framework was performed.
      Furthermore, molecular electrostatic potential maps (MEPs) were obtained and
      analysed. NMR chemical shifts were calculated at ab initio level and further
      compared with previous experimental values; coupling constants were also
      calculated. The stereochemistry of the molecule is thoroughly discussed,
      revealing the key role that hyperconjugative interactions play in defining
      experimental trends. These results show the versatility of geminal spin-spin
      coupling (2)J(C-1',O) as a probe for stereochemical studies of proanthocyanidins.

PMID- 19096887
TI  - PRES (posterior reversible encephalopathy syndrome), a rare complication of
      tacrolimus therapy.
AB  - With increasing numbers of solid organ and hematopoietic stem cell
      transplantations being performed, there have been significant increases in the
      use of immunosuppressive agents such as cyclosporine and tacrolimus. Posterior
      reversible encephalopathy syndrome (PRES) is a serious complication of
      immunosuppressive therapy use following solid organ or stem cell transplants.
      Clinical findings including headache, mental status changes, focal neurological
      deficits, and/or visual disturbances. Associated with these are characteristic
      imaging features of subcortical white matter lesions on computed tomography (CT)
      or magnetic resonance imaging (MRI). The changes in the subcortical white matter
      are secondary to potentially reversible vasogenic edema, although conversion to
      irreversible cytotoxic edema has been described. These imaging findings
      predominate in the territory of the posterior cerebral artery. Many studies have
      shown that the neurotoxicity associated with tacrolimus may occur at therapeutic
      levels. In most cases of PRES, the symptom complex is reversible by reducing the
      dosage or withholding the drug for a few days. While PRES is an uncommon
      complication, it is associated with significant morbidity and mortality if it is
      not expeditiously recognized. MRI represents the most sensitive imaging technique
      for recognizing PRES. This report highlights the value of MRI in prompt
      recognition of this entity, which offers the best chance of avoiding long-term
      sequelae.

PMID- 19096886
TI  - Hospital infections, animal models and alternatives.
AB  - Bacteria represent a threat to human health, especially in healthcare settings,
      and treatment options are limited due to increasingly common antibiotic
      resistance. It is, therefore, imperative that we continue to investigate the
      mechanisms of pathogenesis and host-pathogen interactions. Despite the fact that
      some bacterial pathogens are capable of infecting both humans and at least one
      laboratory animal species, the relevance and animal welfare implications of
      animal infection models are of concern. Here, we consider whether plants and
      lower organisms are suitable candidates to investigate certain aspects of
      bacterial pathogenicity. Indeed, many of the virulence factors employed by micro
      organisms render the capacity to infect a range of hosts. The scope for using
      such models, together with 3D human "organoids", to accelerate the development
      and screening of novel drugs and treatment combinations for bacterial infections
      is considered.

PMID- 19096888
TI  - Special Corner: representational content and cognitive abilities.

PMID- 19096889
TI  - Different venous angioplasty manoeuvres for successful implantation of CRT
      devices.
AB  - AIMS: Cardiac resynchronization therapy (CRT) has growing impact in the treatment
      of severe heart failure Stenosis of coronary veins, complex structure of coronary
      sinus and occlusions of subclavian veins can limit lead passage in the target
      vein. METHODS AND RESULTS: Retrospective analysis of 705 implantation procedures
      of CRT devices from 1999 to July 2007 in a single centre to show the impact of
      venous angioplasty manoeuvres for successful placement of left ventricular lead.
      In 31 patients (3.5%) venous angioplasty was performed for LV-lead placement: 24
      coronary veins (balloons 2.5-4.0 mm), 4 subclavian veins, 3 valves in the
      coronary sinus and one Marshall vein were dilated. Ring like strictures of
      coronary veins made high inflation pressures (16 +/- 4 atm) necessary. Success
      rate of LV lead placement were 99%. Complications were rare. CONCLUSIONS:
      Angioplasty of coronary or subclavian veins and valve structures of coronary
      sinus are a useful and safe tool for successful lead placement. The use of
      balloons of 3.0mm in size usually allows implantation of at least a unipolar
      lead.

PMID- 19096890
TI  - A dramatic storm of idiopathic ventricular fibrillation.

PMID- 19096891
TI  - Communicating the diagnosis of multiple sclerosis: results of a survey among
      Greek neurologists.
AB  - In the frame of current treatment options for multiple sclerosis (MS) and
      recommendations for early intervention, we investigated the practice and
      attitudes of neurologists towards MS-diagnosis communication in Greece. We
      constructed and sent out a 22-item questionnaire to neurologists practising in
      different employment settings and geographic regions in Greece. Overall, 217
      (37.41 %) of 580 neurologists replied. The vast majority (94.9 %) informs the
      patient of a definite MS diagnosis, and 73.6 % do so immediately, but only 41.7 %
      use the term multiple sclerosis. Furthermore, neurologists strongly agreed that
      timing of diagnosis communication depends to a large extent on the individual
      patient's personality (62.5 %) and mental state (52.3 %). Most neurologists (78.7
      %) inform relatives about the diagnosis, but only in the presence of the patient.
      In cases where disclosure was delayed, 59.5 % noted that they did not observe any
      changes as regards the trust or confidence of their patients towards them. Most
      neurologists also noted that education level (72 %) and mental state (51.9 %), at
      the time of disclosure influenced patients who did not fully understand the
      meaning of their diagnosis. This survey provided some useful new findings with
      respect to MS diagnosis communication; however, the questions of how and possibly
      how much to communicate warrant further cross-cultural investigation.

PMID- 19096892
TI  - Treatment of diffuse pigmented villonodular synovitis of the knee with combined
      surgical and radiosynovectomy.
AB  - Treatment of extensive diffuse pigmented villonodular synovitis (PVNS) of large
      joints by isolated surgical resection is unsatisfactory, with high rates of local
      recurrence. Post-synovectomy adjuvant treatment with external beam radiation
      therapy or intra-articular injection of radioactive material as yttrium-90
      ((90)Y) yielded better results. Between January 2005 and January 2007, 12
      patients (eight men and four women aged 19-49 years) with extensive diffuse PVNS
      of the knee were treated. All patients had an adjuvant post-operative external
      beam radiation therapy (2,600-3,000 cGy) conventionally fractionated 200
      cGy/fraction, five fractions/week, 6-8 weeks after surgery. Mean follow-up time
      was 27 months (range from 20 to 36 months). All patients were followed up using
      clinical assessment, magnetic resonance imaging, and plain X-ray. In all
      patients, neither evidence of disease recurrence nor progression of bone or
      articular destruction was noted. No complications were noticed after surgery or
      after post-operative external beam radiation therapy. A combination of debulking
      surgery using anterior and posterior approach with adjuvant post-operative
      external beam radiation therapy for extensive diffuse PVNS of the knee joint is a
      reliable treatment method, with good results in regard to the incidence of local
      recurrence and functional outcome.

PMID- 19096893
TI  - Catastrophic antiphospholipid syndrome triggered by sepsis.

PMID- 19096894
TI  - Dynamics of indirectly transmitted infectious diseases with immunological
      threshold.
AB  - There are numerous examples of human pathogens which persist in environmental
      reservoirs while infectious outbreaks remain rare. In this manuscript, we
      consider the dynamics of infectious diseases for which the primary mode of
      transmission is indirect and mediated by contact with a contaminated reservoir.
      We evaluate the realistic scenario in which the number of ingested pathogens must
      be above a critical threshold to cause infection in susceptible individuals. This
      minimal infectious dose is a consequence of the clearance effect of the innate
      immune system. Infected individuals shed pathogens back into the aquatic
      reservoir, indirectly increasing the transmittability of the pathogen to the
      susceptible. Building upon prior works in the study of cholera dynamics, we
      introduce and analyze a family of reservoir mediated SIR models with a threshold
      pathogen density for infection. Analyzing this family of models, we show that an
      outbreak can result from noninfinitesimal introductions of either infected
      individuals or additional pathogens in the reservoir. We devise two new measures
      of how likely it is that an environmentally persistent pathogen will cause an
      outbreak: (i) the minimum fraction of infected individuals; and (ii) the minimum
      fluctuation size of in-reservoir pathogens. We find an additional control
      parameter involving the shedding rate of infected individuals, which we term the
      pathogen enhancement ratio, which determines whether outbreaks lead to epidemics
      or endemic disease states. Thus, the ultimate outcome of disease is controlled by
      the strength of fluctuations and the global stability of a nonlinear dynamical
      system, as opposed to conventional analysis in which disease reflects the linear
      destabilization of a disease free equilibrium. Our model predicts that in the
      case of waterborne diseases, suppressing the pathogen density in aquatic
      reservoirs may be more effective than minimizing the number of infected
      individuals.

PMID- 19096895
TI  - Traumatic extensor hood rupture.
AB  - We report a traumatic rupture of the extensor hood of the dominant middle finger
      in an elite boxer. Surgical repair of the extensor hood with the
      metacarpophalangeal joint (MCPJ) in 90 degrees of flexion and immobilisation of
      the MCPJ in flexion for 4 weeks allowed successful return of function to an
      international level.

PMID- 19096896
TI  - Use of and communication about dietary supplements among hospitalized patients.
AB  - BACKGROUND: Use of dietary supplements (DS) is common in the United States;
      however little is known about the use of DS specifically in hospitalized
      patients. OBJECTIVE: The goal of this study is to begin to characterize trends in
      DS use by hospitalized patients and to assess the degree of patient-physician
      communication about use of DS that occurs during hospitalization. DESIGN: This is
      a cross-sectional, observational pilot study. PARTICIPANTS: Participants were
      admitted to the general internal medicine or geriatrics service by house staff
      residents; those >or= 18 years of age who were medically stable, cognitively
      intact and fluent in English and/or Spanish were invited to participate in the
      study. RESULTS: Nearly 80% of hospitalized patients reported use of DS, with 52%
      reporting use of non-vitamin/non-mineral DS. During the admission process,
      physicians documented inquiring about DS use only 20% of the time. While the
      majority of patients had no concern about temporarily discontinuing their DS
      during hospitalization, 13% of patients reported that they believed there was
      nothing wrong with continued use of DS while hospitalized regardless of the
      recommendations provided by their inpatient physicians. CONCLUSIONS: Use of DS in
      hospitalized patients is common, and communication between patients and
      physicians regarding their use is limited.

PMID- 19096897
TI  - Patient experiences with coordination of care: the benefit of continuity and
      primary care physician as referral source.
AB  - BACKGROUND: Coordination across a patient's health needs and providers is
      important to improving the quality of care. OBJECTIVES: (1) Describe the extent
      to which adults report that their care is coordinated between their primary care
      physician (PCP) and specialists and (2) determine whether visit continuity with
      one's PCP and the PCP as the referral source for specialist visits are associated
      with higher coordination ratings. DESIGN: Cross-sectional study of the 2007
      Health Tracking Household Survey. PARTICIPANTS: A total of 3,436 adults with a
      PCP and one or more visits to a specialist in the past 12 months. MEASUREMENTS:
      Coordination measures were patient perceptions of (1) how informed and up to date
      the PCP was about specialist care received, (2) whether the PCP talked with the
      patient about what happened at the recent specialist visit and (3) how well
      different doctors caring for a patient's chronic condition work together to
      manage that care. RESULTS: Less than half of respondents (46%) reported that
      their PCP always seemed informed about specialist care received. Visit continuity
      with the PCP was associated with better coordination of specialist care. For
      example, 62% of patients who usually see the same PCP reported that their PCP
      discussed with them what happened at their recent specialist visit vs. 48% of
      those who do not usually see the same PCP (adjusted percentages, p < 0.0001).
      When a patient's recent specialist visit was based on PCP referral (vs. self
      referral or some other source), 50% reported that the PCP was informed and up to
      date about specialist care received (vs. 35%, p < 0.0001), and 66% reported that
      their PCP discussed with them what happened at their recent specialist visit (vs.
      47%, p < 0.0001). CONCLUSIONS: Facilitating visit continuity between the patient
      and PCP, and encouraging the use of the PCP as the referral source would likely
      enhance care coordination.

PMID- 19096898
TI  - Imported fenproporex-based diet pills from Brazil: a report of two cases.
AB  - Banned amphetamine-based anorectics are illicitly imported into the United States
      (US), but little is known regarding the harm these diet pills pose to US
      residents. A 26-year-old woman using imported diet pills presented with a two
      year history of intermittent chest pains, palpitations, headaches and insomnia.
      Urine toxicology screen detected amphetamines and benzodiazepines. Fenproporex
      and chlordiazepoxide were detected in her pills. Her symptoms resolved after she
      stopped using diet pills. A 38-year-old man using imported diet pills presented
      after his occupational urine screen was significantly positive for amphetamine.
      Fenproporex and fluoxetine were detected in his pills. These cases illustrate the
      potential harm from imported prescription diet pills that combine fenproporex
      with benzodiazepines, antidepressants, diuretics, laxatives and other substances.
      Increasing physicians' awareness of imported diet pill use may improve care of
      patients suffering from the pills' many adverse effects.

PMID- 19096899
TI  - Turning and churning: loss of health insurance among adults in Medicaid.

PMID- 19096900
TI  - Rhabdomyolysis after bariatric surgery by Roux-en-Y gastric bypass: a prospective
      study.
AB  - BACKGROUND: Obesity is a worldwide epidemic associated to comorbidities and
      increased mortality. Because it is chronic and recurrent and has little response
      to clinical measures, surgical treatment (bariatric surgery) is a therapeutic
      option frequently used. Different surgical complications have been associated
      with this type of procedure, but there is little knowledge about neuromuscular
      complications. Among the latter, rhabdomyolysis (RML), described a few years ago,
      has not been well characterized to date. METHODS: We have studied 22 consecutive
      patients who underwent surgical treatment with open Roux-en-Y gastric bypass
      (RYGBP) for morbid obesity in a university hospital. A database was created
      including the following information of each patient: gender, age, body mass index
      (BMI), comorbidities, surgical time, pre- and postoperative creatine
      phosphokinase (CPK) dosages, and neuromuscular symptoms after surgery. The main
      outcome measure was the frequency of RML using CPK dosage after 24 h of surgery.
      RML was diagnosed as an increase of more than five times the superior limit of
      normal range of CPK. RESULTS: Fourteen women and eight men were evaluated, with
      median age of 39.9+/-11.2 years, median BMI of 52.4+/-8.0 kg/m2 and mean surgical
      time of 253.2+/-51.9 min. The mean value of postoperative CPK was 7,467.7+/
      12,177.1 IU/L, being greater than 5,000 IU/L in 40.9% of the patients. RML was
      diagnosed in 17 (77.3%) patients. No patient had renal failure caused by RML, but
      there was one death (4.5%) related to abdominal infectious complications.
      Clinical neuromuscular symptoms occurred in 45% of patients, and muscular pain
      was the most common one, especially in gluteus region. Comparative analyzes
      between patients without and with RML diagnosis showed that longer surgical time
      (p=0.005), and occurrence of neuromuscular symptoms (p=0.04) were more common in
      the latter. CONCLUSION: The results of this study are similar to few other
      investigations and confirm that RML in open bariatric surgery with RYGBP
      (Capella) is a common complication. A longer surgical time can be involved in RML
      pathogenesis, and muscular pain is suggestive of RML occurrence.

PMID- 19096901
TI  - Letter to the editor: early outcome of TKA with a medial pivot fixed-bearing
      prosthesis is worse than with a PFC mobile-bearing prosthesis.

PMID- 19096902
TI  - Arthroscopic femoroplasty in the management of cam-type femoroacetabular
      impingement.
AB  - Cam-type femoroacetabular impingement is a recognized cause of intraarticular
      pathology and secondary osteoarthritis in young adults. Arthroscopy is reportedly
      useful to treat selected hip abnormalities and has been proposed as a method of
      correcting underlying impingement. We report the outcomes of arthroscopic
      management of cam-type femoroacetabular impingement. We prospectively assessed
      all 200 patients (207 hips) who underwent arthroscopic correction of cam
      impingement from December 2003 to October 2007, using a modified Harris hip
      score. The minimum followup was 12 months (mean, 16 months; range, 12-24 months);
      no patients were lost to followup. The average age was 33 years with 138 men and
      62 women. One hundred and fifty-eight patients (163 hips) underwent correction of
      cam impingement (femoroplasty) alone while 42 patients (44 hips) underwent
      concomitant correction of pincer impingement. The average increase in Harris hip
      score was 20 points; 0.5% converted to THA. We had a 1.5% complication rate. The
      short-term outcomes of arthroscopic treatment of cam-type femoroacetabular
      impingement are comparable to published reports for open methods with the
      advantage of a less invasive approach.

PMID- 19096903
TI  - Changes in cortical blood oxygenation during arithmetical tasks measured by near
      infrared spectroscopy.
AB  - Solving arithmetical problems is a core skill which is learned starting early in
      childhood and has been shown to involve a temporo-parietal network. In this
      study, we investigated hemodynamic concentration changes in oxygenated (O(2)Hb)
      and deoxygenated hemoglobin (HHb) within cortical brain regions by means of near
      infrared spectroscopy (NIRS). Ten healthy subjects had to calculate or just read
      two-digit addition tasks that were either presented as numeric formulas or
      embedded in text. We found higher increases for O(2)Hb in parietal brain regions
      of both hemispheres for the calculation compared to the reading-only condition.
      Furthermore, these increases were more pronounced during text-embedded tasks than
      during numeric tasks. Corresponding decreases of HHb could also be detected.
      These first NIRS findings on that topic confirm that parietal regions are
      involved in the processing of arithmetic tasks while the amount of activation
      seems to depend on task modalities like difficulty or complexity.

PMID- 19096904
TI  - Complete nucleotide and amino acid sequences and genetic organization of porcine
      kobuvirus, a member of a new species in the genus Kobuvirus, family
      Picornaviridae.
AB  - Kobuvirus is a new genus in the family Picornaviridae. Two species are currently
      known: Aichi virus (human kobuvirus) and Bovine kobuvirus (U-1). In this study,
      the complete nucleotide and amino acid sequences and genetic organization of
      porcine kobuvirus (Kobuvirus/swine/S-1-HUN/2007/Hungary, EU787450) were
      determined. The structure of the S-1-HUN genome, VPg-5'UTR-leader protein
      structural proteins (VP0, VP3, VP1)-non-structural proteins (2A-2C, 3A-3D)-3'UTR
      poly(A) tail, was found to be typical of picornavirus. The 8210-nucleotide (nt)
      long RNA genome contains a large open reading frame (7467 nt) encoding a
      potential polyprotein precursor of 2488 amino acids (aa) that has 57/56% and
      63/64% nt/aa identity with Aichi virus and U-1, respectively. The 5'UTR contains
      a hepacivirus/pestivirus-like internal ribosomal entry site (IRES type IV group-B
      like) with conserved pseudoknot, II and IIIa-f domains. A tandem repeat (a 30
      amino-acid-long motif) was detected in 2B. Thirty-nine (65%) of the 60 fecal
      samples from pigs under the age of 6 months at the tested farm were positive (the
      incidence was 90% under the age of 3 weeks). Porcine kobuvirus belongs to a
      potential new species-the third-in the genus Kobuvirus.

PMID- 19096905
TI  - Systemic gene delivery into soybean by simple rub-inoculation with plasmid DNA of
      a Soybean mosaic virus-based vector.
AB  - Plant virus-based vectors provide attractive and valuable tools for conventional
      transgenic technology and gene function studies in plants. In the present study,
      we established the infectivity of intact plasmid DNA of Soybean mosaic virus
      (SMV) cDNA upon simple rub-inoculation of soybean leaves by utilizing viral
      transcription and processing signals to produce infectious in vivo transcripts.
      Furthermore, we engineered this SMV cDNA clone as a gene delivery vector for
      systemic expression of foreign proteins in soybean. Using this SMV-based vector,
      several genes with different biological activities were successfully expressed
      and stably maintained following serial plant passage in soybean. Thus, DNA
      mediated gene delivery using this SMV-based vector provides a rapid and cost
      effective approach for the overproduction of valuable proteins and for the
      evaluation of new traits in soybean after simple rub-inoculation onto leaves.

PMID- 19096906
TI  - Accumulation of iron and arsenic in the Chandina alluvium of the lower delta
      plain, Southeastern Bangladesh.
AB  - Accumulations of iron, manganese, and arsenic occur in the Chandina alluvium of
      southeastern Bangladesh within 2.5 m of the ground surface. These distinctive
      orange-brown horizons are subhorizontal and consistently occur within 1 m of the
      contact of the aerated (yellow-brown) and water-saturated (gray) sediment. Ferric
      oxyhydroxide precipitates that define the horizons form by oxidation of reduced
      iron in pore waters near the top of the saturated zone when exposed to air in the
      unsaturated sediment. Hydrous Fe-oxide has a high specific surface area and thus
      a high adsorption capacity that absorbs the bulk of arsenic also present in the
      reduced pore water, resulting in accumulations containing as much as 280 ppm
      arsenic. The steep redox gradient that characterizes the transition of saturated
      and unsaturated sediment also favors accumulation of manganese oxides in the
      oxidized sediment. Anomalous concentrations of phosphate and molybdenum also
      detected in the ferric oxyhydroxide-enriched sediment are attributed to sorption
      processes.

PMID- 19096907
TI  - Immunohistochemical detection of p53 protein in basal cell skin cancer after
      microwave-assisted antigen retrieval.
AB  - p53 is the most frequently altered tumor-suppressor gene in skin cancer. In
      normal tissues the p53 protein (wild type) has a very short half-life and it is
      not detectable immunohistochemically. In contrast, the mutant p53 protein has an
      extended half-life in tumor cells and can be detected by immunohistochemical
      methods. p53 is widely used as an indicator of tumor aggression and progression.
      Fixation methods especially formaldehyde based fixation may mask the
      immunohistochemical detection of p53 protein but antigen retrieval methods
      enhance the inmmunohistochemical detection of p53 protein by remodification of
      protein structure. This study was designed to evaluate the efficacy of different
      fixatives, of microwaving and microwave pretreatment method to retrieve p53
      immunoreactivity in paraffin-embedded non-lesioned (adjacent normal tissue) human
      skin samples or pathological human skin samples diagnosed as basal cell
      carcinoma. The samples were fixed at RT and/or in microwave oven either in
      neutral buffered formalin or alcohol for different time periods. For antigen
      retrieval, the sections were irradiated in a microwave oven for 5 cycles in 10 mM
      citrate buffer (pH 6.00). In this study the effects of six different fixation
      methods on the immunohistochemical staining have been investigated in basal cell
      tumor specimens. The application of antigen retrieval method was also examined
      and compared. Optimal results were obtained using samples fixed in alcohol either
      at room temperature (24 h) or in microwave oven.

PMID- 19096908
TI  - Comparative study based on sediment characteristics and macrobenthic communities
      in two Italian lagoons.
AB  - The aims of this study were to analyse sediment characteristics and macrobenthic
      assemblages in two very close Italian coastal lagoons (Lesina and Varano) and to
      assess the different behaviour between the two basins and the relationship
      between sediment matrix and benthic organisms within and between the two lagoons.
      The comparative study was performed in July 2007 at 13 sampling sites in Lesina
      lagoon and 15 sites in Varano basin for sediment grain size, total organic carbon
      (TOC), total nitrogen (TN), total phosphorus (TP) and macrobenthic structure
      analyses. Both lagoons were generally dominated by fine-grained sediments (clay
      and silt components). The average contents of TOC and TN measured in Lesina was
      higher than in Varano (3.31% vs 2.52% for TOC and 5,200 microg.g(-1) vs 3,713
      microg.g(-1) for TN); in contrast, the TP was lower (540 microg.g(-1) vs 620
      microg.g(-1)). Based on macrobenthic community patterns, the central zone in
      Varano lagoon and the eastern area in Lesina lagoon were characterised by the
      lowest abundance (168.7 ind.m(-2) and 503.2 ind.m(-2), respectively) and by the
      lowest number of species, as highlighted by the diversity indices (Shannon
      Wiener, H' range was 0.47-1.45 for Lesina and 0.00-1.68 for Varano; Margalef
      species richness, d range was 0.00-1.67 for Lesina lagoon and 0.00-2.38 for
      Varano basin). Ordination diagrams suggested an influence of marine and
      freshwater inputs on the sediment distribution in Varano lagoon and on
      macrobenthic assemblages in Lesina lagoon.

PMID- 19096909
TI  - Groundwater quality mapping in urban groundwater using GIS.
AB  - Konya City, located in the central part of Turkey, has grown and urbanized
      rapidly. A large amount of the water requirement of Konya City is supplied from
      groundwater. The quality of this groundwater was determined by taking samples
      from 177 of the wells within the study area. The purposes of this investigation
      were (1) to provide an overview of present groundwater quality and (2) to
      determine spatial distribution of groundwater quality parameters such as pH,
      electrical conductivity, Cl-, SO4(-2), hardness, and NO3- concentrations, and (3)
      to map groundwater quality in the study area by using GIS and Geostatistics
      techniques. ArcGIS 9.0 and ArcGIS Geostatistical Analyst were used for generation
      of various thematic maps and ArcGIS Spatial Analyst to produce the final
      groundwater quality map. An interpolation technique, ordinary kriging, was used
      to obtain the spatial distribution of groundwater quality parameters. The final
      map shows that the southwest of the city has optimum groundwater quality, and, in
      general, the groundwater quality decreases south to north of the city; 5.03%
      (21.51 km2) of the total study area is classified to be at the optimum
      groundwater quality level.

PMID- 19096910
TI  - On the intensity and type transition of land use at the basin scale using RS/GIS:
      a case study of the Hanjiang River Basin.
AB  - The purpose of this study is to investigate the land use intensity and land use
      change type at the basin scale in the middle and lower reaches of the Hanjiang
      River Basin (in Hubei Province, China) by combining the Landsat TM images in 1995
      and 2000 with the land use database (in scale 1:10,000) and relative data. In
      this study, the basic data is acquired from the interpretation of remote sensing
      (RS) images. The intensity of land use and the rate of change in double
      directions of land use dynamics are calculated with the support of software
      ARC/INFO. The intensity of land use is indicated by the intensity coefficient of
      land use, and the transition of land use types is quantified as the rate of
      change in double-direction of land use types and also expressed as the transition
      matrix of land use types. The results are expressed in space by Geographic
      Information System (GIS) software. Results of this study show that (1) the
      intensity of land use is high in the study region, the intensity coefficients of
      land use in 1995 and 2000 are 260.025 and 290.526, respectively, and the
      intensity of development and utilization of land is trend to increscent; and (2)
      the rate of land use change in double directions in the whole study region is
      0.52 with great spatial variation and the differentiation of land use types. In
      the differentiation of land use types, the unutilized land (with the rate to
      4.391) is developed fast, the grassland (with 2.836) and water area (with 1.664)
      are disturbed severely, and these changes will influence the eco-environment in
      the Hanjiang River Basin and all the Yangtze Basin. The rates of the farmland and
      the woodland are 0.424 and 0.344, respectively, meaning that the fundamentals of
      regional human-environmental system are relative stable. With this study, we can
      conclude that (1) the patterns of land use are increasingly changing in the study
      region, the environmental impacts are escalated on this stage, and the further
      outcomes are destined to change the stability of the regional human-environmental
      system; and (2) the most useful method to study the present land use and its
      change is through the use of the RS/GIS with the land use database (in scale
      1:10,000).

PMID- 19096911
TI  - A methodology for treating missing data applied to daily rainfall data in the
      Candelaro River Basin (Italy).
AB  - Environmental time series are often affected by the "presence" of missing data,
      but when dealing statistically with data, the need to fill in the gaps estimating
      the missing values must be considered. At present, a large number of statistical
      techniques are available to achieve this objective; they range from very simple
      methods, such as using the sample mean, to very sophisticated ones, such as
      multiple imputation. A brand new methodology for missing data estimation is
      proposed, which tries to merge the obvious advantages of the simplest techniques
      (e.g. their vocation to be easily implemented) with the strength of the newest
      techniques. The proposed method consists in the application of two consecutive
      stages: once it has been ascertained that a specific monitoring station is
      affected by missing data, the "most similar" monitoring stations are identified
      among neighbouring stations on the basis of a suitable similarity coefficient; in
      the second stage, a regressive method is applied in order to estimate the missing
      data. In this paper, four different regressive methods are applied and compared,
      in order to determine which is the most reliable for filling in the gaps, using
      rainfall data series measured in the Candelaro River Basin located in South
      Italy.

PMID- 19096912
TI  - Impact of sampling strategy on stream load estimates in till landscape of the
      Midwest.
AB  - Accurately estimating various solute loads in streams during storms is critical
      to accurately determine maximum daily loads for regulatory purposes. This study
      investigates the impact of sampling strategy on solute load estimates in streams
      in the US Midwest. Three different solute types (nitrate, magnesium, and
      dissolved organic carbon (DOC)) and three sampling strategies are assessed.
      Regardless of the method, the average error on nitrate loads is higher than for
      magnesium or DOC loads, and all three methods generally underestimate DOC loads
      and overestimate magnesium loads. Increasing sampling frequency only slightly
      improves the accuracy of solute load estimates but generally improves the
      precision of load calculations. This type of investigation is critical for water
      management and environmental assessment so error on solute load calculations can
      be taken into account by landscape managers, and sampling strategies optimized as
      a function of monitoring objectives.

PMID- 19096913
TI  - Three-generational alkaptonuria in a non-consanguineous family.
AB  - OBJECTIVE: Alkaptonuria (AKU) is a rare inborn error of metabolism of aromatic
      amino acids and considered to be an autosomal recessive trait caused by mutations
      in the homogentisate 1,2-dioxygenase (HGD) gene. A dominant pattern of
      inheritance has been reported but was attributed to extended consanguinity in
      many cases. However, we have observed a non-consanguineous family segregating AKU
      in a dominant manner over three generations. RESULTS: All affected individuals
      presented with typical features of AKU including darkening of the urine,
      ochronosis, arthropathy, and elevated urinary excretion of homogentisic acid.
      Sequence analysis of the HGD gene from genomic DNA of two affected individuals,
      uncle and niece, revealed a heterozygous missense mutation (M368V) in the uncle
      that was not present in his niece. Microsatellite genotyping demonstrated that
      both were heterozygous at the HGD locus and shared one haplotype. This haplotype
      did not contain a detectable HGD mutation. The haplotype was also found in a
      healthy son of the niece, making a dominant HGD mutation unlikely. Moreover,
      sequencing of cDNA from lymphoblastoid cells of the niece did not reveal an HGD
      mRNA with a potentially dominant-negative effect. CONCLUSION: Rare causes of the
      uncommon AKU inheritance in this family have to be considered, ranging from the
      coincidence of undetectable HGD mutations to a dominant mutation of a second,
      hitherto unknown AKU gene.

PMID- 19096914
TI  - Metabolic programming: Role of nutrition in the immediate postnatal life.
AB  - Although genes and dietary habits are generally implicated in the aetiology of
      the prevailing obesity epidemic, the steep increase in the incidence of obesity
      within a relatively short span of time suggests that other contributing factors
      may be at play. The role of nutritional experience during the very early periods
      of life is increasingly being recognized as contributing to growth and metabolic
      changes in later life. Epidemiological data and studies from animal models have
      established a strong correlation between an aberrant intrauterine environment and
      adult-onset disorders in offspring. The nutritional experience in the immediate
      postnatal life is another independent factor contributing to the development of
      metabolic diseases in adulthood. Although studies on the small-litter rat model
      have shown that overnourishment during the suckling period results in adult-onset
      metabolic disorders, our studies have shown that a change in the quality of
      calories-specifically, increased carbohydrate intake by newborn rat pups in the
      immediate postnatal period-results in chronic hyperinsulinaemia and adult-onset
      obesity. Several functional alterations in islets and in the hypothalamic energy
      homeostatic mechanism appear to support this phenotype. Remarkably, female rats
      that underwent the high-carbohydrate dietary modification as neonates
      spontaneously transmitted the obesity phenotype to their offspring, thus
      establishing a vicious generational effect. The high-carbohydrate diet-fed rat
      model has particular relevance in the context of the current human infant feeding
      practices: reduction in breast feeding and increase in formula feeding for
      infants, accompanied by early introduction of carbohydrate-enriched baby foods.

PMID- 19096915
TI  - PIG11 is involved in hepatocellular carcinogenesis and its over-expression
      promotes Hepg2 cell apoptosis.
AB  - PIG11 (p53-induced gene 11) is a p53 target gene and candidate tumour suppressor
      gene. In this study, the expression of PIG11 protein was detected in human
      hepatocellular carcinoma (HCC) and normal liver tissues with an
      immunohistochemical method. Compared with expression in human normal liver
      tissues, the expression of PIG11 protein was significantly down-regulated in
      human HCC tissues. In addition, a recombinant pLXSN-PIG11 retroviral vector was
      constructed and transfected into HepG2 cells (human hepatocellular carcinoma cell
      line) and the role of PIG11 in apoptosis was analyzed. The percentage (18.60%) of
      apoptotic cells transfected with pLXSN-PIG11 was higher than that in cells
      transfected with pLXSN only (6.03%) or the vehicle control (3.81%) (P < 0.01).
      DNA gel electrophoresis showed a clear DNA ladder in pLXSN-PIG11-infected HepG2
      cells. Our results suggested that the PIG11 gene is involved in carcinogenesis
      and development of hepatocarcinoma. Therefore, PIG11 is considered to be a new
      candidate liver tumour suppressor gene, and may play an important role in tumour
      suppression through promotion of cell apoptosis.

PMID- 19096917
TI  - Competition between energy transfer quenching and chelation enhanced fluorescence
      in a Cu (II) coordinated conjugated polymer system.
AB  - An investigation of the mechanism of the fluorescence quenching by Cu(2+) for a
      conjugated polymer system initially designed as a fluorescence "turn-on"
      chemosensor based on chelation enhanced fluorescence (CHEF) is described in this
      paper. Unlike all other metal cations tested, the polymer/Cu(2+) hybrid system
      with a 1:1 ratio between the receptor and Cu(2+) has only weak fluorescence with
      lambda(max) = 490 nm and a quantum yield of 0.004 in THF at room temperature. In
      solvent glasses at 77 K the fluorescence remained quenched suggesting that the
      quenching mechanism was due to energy transfer between the Cu(2+) and the
      conjugated polymer backbone. The energy transfer quenching competes effectively
      with the electron transfer involved in the CHEF resulting in a more selective
      chemosensory system.

PMID- 19096918
TI  - The construction of "cultural difference" and its therapeutic significance in
      immigrant mental health services in France.
AB  - Since the early 1970s, the French public health system has been accorded
      considerable responsibility for immigrants identified by the educational,
      judicial or social service authorities as psychologically distressed or socially
      disruptive. In this paper we discuss three models of healing embedded in
      constructs of "cultural difference" and addressed at specialized mental health
      care centers catering to immigrants in Paris: "cultural mediation," transcultural
      psychiatry/ethnopsychiatry and clinical medical anthropology. Based on
      observations and interviews at three specialized mental health centers in Paris,
      we explore how these clinical approaches address migrant wellbeing and seek to
      resolve crises in migrant families, especially those of West African origin. We
      suggest that the prevalent approaches to therapy creatively blend concepts and
      practices of anthropology, psychiatry and psychology but, at the same time,
      confront challenges inherent in the use of a generic "African" healing modality.
      Cases studies demonstrate that in order for such interventions to be perceived as
      effective by patients, "cultural difference" must be acknowledged but also
      situated in broader social, political and economic contexts.

PMID- 19096916
TI  - Presence of myofibroblasts and expression of matrix metalloproteinase-2 (MMP-2)
      in ameloblastomas correlate with rupture of the osseous cortical.
AB  - Myofibroblasts are frequent in the stroma of neoplasm and by the expression of
      proteinases they can influence tumor infiltration and progression. In the present
      study, presence of myofibroblasts and expression of matrix metalloproteinase-2
      (MMP-2) and urokinase plasminogen activator (uPA) were examined in intra-osseous
      solid multicystic ameloblastomas to determine their roles in the
      clinicopathological features of the tumors. Fifty seven ameloblastomas were
      analyzed immunohistochemically with antibodies against the isoform alpha of the
      smooth muscle actin (alpha-SMA), a specific marker of myofibroblasts, MMP-2 and
      uPA. Myofibroblasts were found in the stroma, in close contact with neoplastic
      cell islands, of approximately 58% (n = 33) of the ameloblastomas. MMP-2 and uPA
      were found in the cytoplasm of both neoplastic and stromal cells. A significant
      correlation between presence of myofibroblasts and MMP-2 expression was observed.
      Abundant presence of myofibroblast in the stroma of the tumors and expression of
      MMP-2 in the neoplastic or stromal cells were significantly correlated with
      rupture of the osseous cortical, which has been considered an important
      prognostic marker of ameloblastoma aggressiveness. Ours results suggest that
      abundant presence of myofibroblasts and expression of MMP-2 in solid
      ameloblastomas may be associated with a more aggressive infiltrative behavior.

PMID- 19096919
TI  - Edematogenic activity of scorpion venoms from the Buthidae family and the role of
      platelet-activating factor and nitric oxide in paw edema induced by Tityus
      venoms.
AB  - We compared the edematogenic activity of venoms of scorpions from the Buthidae
      family, Tityus bahiensis (Tbv), Tityus serrulatus (Tsv) and Rhopalurus rochai
      (Rrv). Three doses (20, 40 and 80 microg/kg sc) of each venom were administrated
      in hind paw of mice and edema was measured from 5 min to 24 h. Tbv and Tsv both
      induced edema of rapid onset (135% of increase at 15 min); Rrv induced only a
      mild edema (40% of increase). We then investigated the involvement of platelet
      activating factor (PAF) and endogenous nitric oxide (NO) in Tbv and Tsv-induced
      paw edema. Pretreatment of mice with a PAF antagonist (WEB-2170) inhibited Tsv
      but not Tbv-induced edema. Pretreatment with a non selective inhibitor of NO
      synthases (L: -NAME) inhibited or increased the edema depending on the dose and
      the time the edema was measured. In conclusion, the venoms from Tityus are
      stronger inducers of edema than the venom from the Rhopalurus scorpion. The
      venoms of Tityus species are similar in potency and time-course edema
      development. PAF is involved in the edema induced only by Tsv.

PMID- 19096920
TI  - Early systemic inflammatory response to drug-eluting stents implantation: the
      heart of the difference? Editorial to: "Comparison of changes in early
      inflammatory markers between sirolimus- and paclitaxel-eluting stent
      implantation" by Li et al.

PMID- 19096922
TI  - Vaginal vibrator in the rectum of a young man.

PMID- 19096921
TI  - Trial design challenges when combining medication and parent training in children
      with pervasive developmental disorders.
AB  - This paper presents the rationale for a 24-week, randomized trial designed to
      test whether risperidone plus structured parent training would be superior to
      risperidone only on measures of noncompliance, irritability and adaptive
      functioning. In this model, medication reduces tantrums, aggression and self
      injury; parent training promotes improvement in noncompliance and adaptive
      functioning. Thus, medication and parent training target related, but separate,
      outcomes. At week 24, the medication was gradually withdrawn to determine whether
      subjects in the combined treatment group could be managed on a lower dose or off
      medication without relapse. Both symptom reduction and functional improvement are
      important clinical treatment targets. Thus, experimental evidence on the
      beneficial effects of combining pharmacotherapy and exportable behavioral
      interventions is needed to guide clinical practice.

PMID- 19096923
TI  - Cross-fostering effects on weight, exploratory activity, acoustic startle reflex
      and corticosterone stress response in Norway gray rats selected for elimination
      and for enhancement of aggressiveness towards human.
AB  - Two rat lines, one tame, the other aggressive, differing by many behavioral
      features and stress reactivity were developed by long-term selection of wild gray
      rats for elimination and enhancement of aggressiveness towards humans. The aim of
      this work was to study the role of the maternal environment in the expression of
      these differences between the two rat lines using the cross-fostering paradigm.
      Fostering of tame rats of both sexes by aggressive mothers and aggressive females
      by tame mothers was without effect on behavior score towards humans, but the
      cross-fostered aggressive males had a small, yet significant, increase in
      aggressiveness score. Cross-fostering revealed that exploratory behavior in the
      hole-board test and the acoustic startle amplitude were weakly affected by
      maternal interactions, although there was an effect on body weight and on the
      stress corticosterone response. Body weight was decreased in tame males fostered
      by aggressive mothers only and it was increased in cross-fostered aggressive rats
      of both sexes. Fostering of tame males and females by an aggressive mother
      enhanced almost twofold the corticosterone response immediately after stress,
      while fostering of aggressive ratlings of both sexes by a tame mother was without
      effect. The current results demonstrated that the maternal postnatal environment
      had no substantial effect on the behavioral responses of both tame and aggressive
      rats, but it possibly contributed to the development of the corticosterone
      response to restraint stress in the tame, and not the aggressive rats, i.e. these
      effects of cross-fostering were dependent on ratling genotype.

PMID- 19096924
TI  - Barriers and facilitators in implementing illness management and recovery for
      consumers with severe mental illness: trainee perspectives.
AB  - We conducted an on-line survey of clinicians who attended training on illness
      management and recovery (IMR) to identify the extent of implementation and
      barriers and facilitators of IMR practice. Of 89 direct service providers, 50.6%
      reported using the formal IMR curriculum, 25.8% reported using parts of IMR, and
      23.6% never used IMR following training. Factor analysis of facilitator items
      revealed three internally consistent factors: agency leadership support, program
      level structure, and job-related structural support. Participants who used formal
      IMR endorsed a greater percentage of overall facilitators, and scored higher on
      each of the three factors of agency leadership support, program-level structures
      (e.g., fidelity reports) and job-related structures (e.g., presence of weekly
      supervision). In addition to training and toolkit materials, attention needs to
      be given to other elements to support IMR implementation.

PMID- 19096925
TI  - Improvement of embryonic development and production of offspring by transferring
      meiosis-II chromosomes of senescent mouse oocytes into cytoplasts of young mouse
      oocytes.
AB  - PURPOSE: The effects of reciprocal transplantation of meiosis-II chromosomes
      between senescent and young mouse oocytes were evaluated based on pre- and post
      implantation development ability of resultant embryos. METHODS: Karyoplasts
      including meiosis-II chromosomes of oocytes from senescent Rockefeller mouse/Ms
      Rb(6, 15) females (10 to 12 months, age-related infertile mice) were transferred
      into cytoplasts of oocytes from young F(1) females (3 to 5 months). Reconstructed
      oocytes were fertilized in vitro, and then the resultant embryos were cultured in
      vitro and transferred to recipient mice. RESULTS: The reconstructed oocytes that
      consisted of aged-karyoplasts and young-cytoplasts showed significantly improved
      embryonic development (from 23.2% to 30.0%) and development to term (from 6.3% to
      27.1%, P < 0.05) as compared with the oocytes reconstructed from young
      karyoplasts and aged-cytoplasts. CONCLUSIONS: The present study showed successful
      rejuvenation for age-related infertility using transplantation of meiosis-II
      chromosomes in animal experimental models.

PMID- 19096926
TI  - Predicting treatment and follow-up attrition in parent-child interaction therapy.
AB  - Predictors of attrition from individual parent-child interaction therapy were
      examined for 99 families of preschoolers with disruptive behavior disorders.
      Seventy-one percent of treatment dropouts were identified by lower SES, more
      maternal negative talk, and less maternal total praise at pretreatment. Following
      PCIT, families were randomly assigned to an Assessment-Only or Maintenance
      Treatment condition. Higher maternal distress predicted 63% of dropouts in the
      Assessment-Only condition. Lower maternal intellectual functioning predicted 83%
      of dropouts from Maintenance Treatment. Findings highlight a continuing need for
      evidence-based retention strategies at various phases of engagement in PCIT.

PMID- 19096927
TI  - High ISSR variation in 14 surviving individuals of Euryodendron excelsum
      (Ternstroemiaceae) endemic to China.
AB  - Euryodendron excelsum is a critically endangered Ternstroemiaceae species endemic
      to southern China, with only 14 individuals surviving in Ba Jia Zhen of Yangchun,
      Guangdong Province. Intersimple sequence repeat (ISSR) markers were used to
      assess genetic variation and relationships among these individuals. Population
      genetic parameters were estimated by a Bayesian approach as well as conventional
      methods. Of the 225 loci generated by 21 primers, 147 (65.33%) were polymorphic.
      Compared with other species of Theaceae and related families, a high level of
      genetic variation was identified in E. excelsum (Nei's gene diversity, 0.2458;
      Shannon's index, 0.3626). An unweighted pair group method with arithmetic mean
      (UPGMA) dendrogram showed that the 14 individuals were mainly clustered into
      three groups, a conclusion further supported by principal coordinate analysis.
      Based on these results, a management and conservation strategy for E. excelsum
      was proposed.

PMID- 19096928
TI  - Expression of vitellogenin and transferrin in activated ovaries of worker honey
      bees, Apis mellifera.

PMID- 19096929
TI  - Plasma carotenoids, tocopherols, retinol and breast cancer risk: results from the
      Shanghai Women Health Study (SWHS).
AB  - Evidence from some previous studies suggests that lipophilic antioxidants,
      particularly carotenoids, may reduce the risk of breast cancer. We prospectively
      investigated the associations of plasma levels of tocopherols, retinol,
      carotenoids with the risk of developing breast cancer among Chinese women. We
      conducted a study of 365 incident breast cancer cases and 726 individually
      matched controls nested within a large cohort study of women aged 40-70 years at
      baseline. We observed no associations between breast cancer risk and any of the
      tocopherols, retinol, and most carotenoids. However, high levels of plasma
      lycopene other than trans, 5- and 7-cis or trans alpha-cryptoxanthin were
      inversely associated with the risk of developing breast cancer. Our results do
      not support an overall protective effect of lipophilic antioxidants on breast
      cancer risk. The few inverse associations observed for subtype of carotenoids may
      need to be confirmed in future studies.

PMID- 19096930
TI  - The role of thyroid hormone nuclear receptors in the heart: evidence from
      pharmacological approaches.
AB  - This review evaluates the hypothesis that the cardiac effects of amiodarone can
      be explained-at least partly-by the induction of a local 'hypothyroid-like
      condition' in the heart. Evidence supporting the hypothesis comprises the
      observation that amiodarone exerts an inhibitory effect on the binding of T3 to
      thyroid hormone receptors (TR) alpha-1 and beta-1 in vitro, and on the expression
      of particular T3-dependent genes in vivo. In the heart, amiodarone decreases
      heart rate and alpha myosin heavy chain expression (mediated via TR alpha-1), and
      increases sarcoplasmic reticulum calcium-activated ATPase and beta myosin heavy
      chain expression (mediated via TR beta-1). Recent data show a significant
      similarity in expression profiles of 8,435 genes in the heart of hypothyroid and
      amiodarone-treated animals, although similarities do not always exist in
      transcripts of ion channel genes. Induction of a hypothyroid cardiac phenotype by
      amiodarone may be advantageous by decreasing energy demands and increasing energy
      availability.

PMID- 19096933
TI  - Good policy follows good science: using criteria and indicators for assessing
      sustainable biofuel production.
AB  - Developing scientific criteria and indicators should play a critical role in
      charting a sustainable path for the rapidly developing biofuel industry. The
      challenge ahead in developing such criteria and indicators is to address the
      limitations on data and modeling.

PMID- 19096931
TI  - Phosphodiesterase inhibition in heart failure.
AB  - Drugs that inhibit cyclic nucleotide phosphodiesterase activity act to increase
      intracellular cyclic adenosine monophosphate (cAMP) and cyclic guanosine
      monophosphate (cGMP) content. In total, 11 families of these enzymes-which differ
      with respect to affinity for cAMP and cGMP, cellular expression, intracellular
      localization, and mechanisms of regulation-have been identified. Inhibitors of
      enzymes in the PDE3 family of cyclic nucleotide phosphodiesterases raise
      intracellular cAMP content in cardiac and vascular smooth muscle, with inotropic
      and, to a lesser extent, vasodilatory actions. These drugs have been used for
      many years in the treatment of patients with heart failure, but their long-term
      use has generally been shown to increase mortality through mechanisms that remain
      unclear. More recently, inhibitors of PDE5 cyclic nucleotide phosphodiesterases
      have been used as cGMP-raising agents in vascular smooth muscle. With respect to
      cardiovascular disease, there is evidence that these drugs are more efficacious
      in the pulmonary than in the systemic vasculature, for which reason they are used
      principally in patients with pulmonary hypertension. Effects attributable to
      inhibition of myocardial PDE5 activity are less well characterized. New
      information indicating that enzymes from the PDE1 family of cyclic nucleotide
      phosphodiesterases constitute the majority of cAMP- and cGMP-hydrolytic activity
      in human myocardium raises questions as to their role in regulating these
      signaling pathways in heart failure.

PMID- 19096932
TI  - Vasodilators in the treatment of acute heart failure: what we know, what we
      don't.
AB  - Although we have recently witnessed substantial progress in management and
      outcome of patients with chronic heart failure, acute heart failure (AHF)
      management and outcome have not changed over almost a generation. Vasodilators
      are one of the cornerstones of AHF management; however, to a large extent, none
      of those currently used has been examined by large, placebo-controlled, non
      hemodynamic monitored, prospective randomized studies powered to assess the
      effects on outcomes, in addition to symptoms. In this article, we will discuss
      the role of vasodilators in AHF trying to point out which are the potentially
      best indications to their administration and which are the pitfalls which may be
      associated with their use. Unfortunately, most of this discussion is only
      partially evidence based due to lack of appropriate clinical trials. In general,
      we believe that vasodilators should be administered early to AHF patients with
      normal or high blood pressure (BP) at presentation. They should not be
      administered to patients with low BP since they may cause hypotension and
      hypoperfusion of vital organs, leading to renal and/or myocardial damage which
      may further worsen patients' outcome. It is not clear whether vasodilators have a
      role in either patients with borderline BP at presentation (i.e., low-normal) or
      beyond the first 1-2 days from presentation. Given the limitations of the
      currently available clinical trial data, we cannot recommend any specific agent
      as first line therapy, although nitrates in different formulations are still the
      most widely used in clinical practice.

PMID- 19096934
TI  - Comparative study of three analysis methods (TTGE, flow cytometry and HPLC) for
      xenobiotic impact assessment on phytoplankton communities.
AB  - The impacts of the fungicide Opus (epoxiconazole) on marine phytoplankton
      communities were assessed in a 12-day field experiment using in situ microcosms
      maintained underwater at 6 m depth. Three community analysis methods were
      compared for their sensitivity threshold in fungicide impact detection. When
      phytoplankton communities were exposed to 1 microg l(-1) of epoxiconazole, no
      effects could be demonstrated using TTGE (Temporal Temperature Gradient gel
      Electrophoresis), flow cytometry or HPLC. When exposed to 10 microg l(-1), TTGE
      fingerprints from PCR amplified 18S rDNA of communities exhibited significant
      differences compared with controls (ANOSIM, P = 0.028). Neither flow cytometry
      counts, nor HPLC pigment profiles allowed to show significant differences in
      microcosms exposed to 10 microg l(-1) of epoxiconazole. When exposed to 100
      microg l(-1), all three methods allowed to detect significant differences in
      treated microcosms, as compared to controls. The TTGE analysis appears in this
      study as the most sensitive method for fungicide impact assessment on eukaryote
      microbial communities.

PMID- 19096936
TI  - Promoting a social justice approach to prevention: future directions for
      training, practice, and research.
AB  - The final paper of this special issue devoted to prevention and social justice
      calls for prevention practitioners and researchers to redirect their energy and
      resources to creating genuine social change. To begin, the contribution of the
      American Psychological Association ethical code to social justice-oriented
      prevention work is explored, and significant ethical issues that need to be
      further addressed by the current code are briefly outlined. Second, we discuss
      the implications of a social justice approach to prevention for training,
      practice and research. Finally, we invite readers to take the lead in putting a
      social justice prevention approach into practice.

PMID- 19096937
TI  - The associations between area of residence, sexual violence victimization, and
      asthma episodes among US adult women in 14 states and territories, 2005-2007.
AB  - Gaps in understanding of how area-based differences in exposure to violence are
      associated with asthma prevalence may limit the development of effective
      prevention programs and the identification of risk for asthma episodes. The
      current investigation examines the associations between sexual violence
      victimization and asthma episodes among US adult women across three different
      metropolitan settings. The association between sexual assault victimizations and
      asthma attacks in the past year was examined using data from the 2005, 2006, and
      2007 Behavioral Risk Factor Surveillance System surveys. Cross-sectional analyses
      were based on adult women with current asthma (n = 4,099). Multivariate logistic
      regression models were used to identify associations between four categories of
      sexual violence victimization and asthma episodes across three categories of
      metropolitan and non-metropolitan settings. Our findings show that unwanted
      touching, attempted unwanted intercourse, forced unwanted intercourse, and any
      sexual violence victimization (touching, attempted intercourse, or forced
      intercourse) were significantly associated with asthma episodes (OR(adj.) = 3.67,
      95% CI, 1.76-7.69; OR(adj.) = 1.77, 95% CI, 1.32-2.37; OR(adj.) = 2.24, 95% CI,
      1.64-3.05, and OR(adj.) = 1.93, 95% CI, 1.47-2.53, respectively). While no
      significant differences in the associations between asthma episodes and
      metropolitan status were found, a significant interaction between non
      metropolitan areas and attempted sexual intercourse was identified (OR(adj) =
      0.53, 95% CI, 0.29-0.96). Sexual victimization appears to be an important, but
      understudied, correlate of asthma morbidity among adult women in the USA,
      suggesting that additional research is needed to better understand the
      associations between sexual violence, psychological distress, and asthma.

PMID- 19096938
TI  - Taxonomic identification and use of free and entrapped cells of a new
      Mycobacterium sp., strain Spyr1 for degradation of polycyclic aromatic
      hydrocarbons (PAHs).
AB  - A polycyclic aromatic hydrocarbon (PAH)-degrading bacterial strain Spyr1 was
      isolated from Greek creosote polluted soil by an enrichment method using pyrene
      as sole carbon and energy source. Spyr1 was identified as Mycobacterium sp. based
      on 16S rDNA analysis and it was capable of degrading pyrene, fluoranthene,
      fluorene, anthracene, and acenaphthene. The effect of entrapment in glass beads
      and alginate/starch mixtures on the survival and pyrene degradation ability of
      Spyr1 cells in liquid suspensions and soil microcosms was tested and compared
      with that of freely suspended cells. In general, free cells showed higher
      degradation of pyrene and other PAH than immobilized cells. However, immobilized
      cells could better tolerate PAH and they maintained their viability and PAH
      degradation capability for at least 1 year after storage at 4 degrees C.
      Entrapped cells in glass beads exhibited better pyrene biodegradation performance
      than alginate/starch entrapped cells in liquid suspensions and could be used
      effectively for at least ten repeated cycles. Alginate/starch entrapped cells
      exhibited better yields than glass beads entrapped cells for removing pyrene as
      well as mixtures of PAH in soil microcosms.

PMID- 19096939
TI  - Assessment of xylanase activity in dry storage as a potential method of reducing
      feedstock cost.
AB  - Enzymatic preprocessing of lignocellulosic biomass in dry storage systems has the
      potential to improve feedstock characteristics and lower ethanol production
      costs. To assess the potential for endoxylanase activity at low water contents,
      endoxylanase activity was tested using a refined wheat arabinoxylan substrate and
      three commercial endoxylanases over the water activity range 0.21-1.0,
      corresponding to water contents of 5% to >60% (dry basis). Homogeneously mixed
      dry samples were prepared at a fixed enzyme to substrate ratio and incubated in
      chambers at a variety of fixed water activities. Replicates were sacrificed
      periodically, and endoxylanase activity was quantified as an increase in reducing
      sugar relative to desiccant-stored controls. Endoxylanase activity was observed
      at water activities over 0.91 in all enzyme preparations in less than 4 days and
      at a water activity of 0.59 in less than 1 week in two preparations. Endoxylanase
      activity after storage was confirmed for selected desiccant-stored controls by
      incubation at 100% relative humidity. Water content to water activity
      relationships were determined for three lignocellulosic substrates, and results
      indicate that two endoxylanase preparations retained limited activity as low as
      7% to 13% water content (dry basis), which is well within the range of water
      contents representative of dry biomass storage. Future work will examine the
      effects of endoxylanase activity toward substrates such as corn stover, wheat
      straw, and switchgrass in low water content environments.

PMID- 19096940
TI  - Primary small cell neuroendocrine carcinoma of the kidney: morphological,
      immunohistochemical, ultrastructural, and cytogenetic study of a case and review
      of the literature.
AB  - Poorly differentiated neuroendocrine carcinomas (PDNECs) of the kidney are
      extremely rare high-grade cancers accounting for only 42 cases reported in the
      literature. In this paper, we describe the morphological, immunohistochemical,
      ultrastructural, and for the first time, cytogenetic features of a renal PDNEC.
      In addition, we have reviewed the literature and compared the published
      clinicopathological data with our morphological and genetic results. The tumor
      arose within the kidney parenchyma and showed the typical histological features
      of a pure small cell PDNEC. Fluorescence in situ hybridization study demonstrated
      a complex chromosomal assessment indicative of a high degree of chromosome
      instability with gain of multiple chromosomes, loss of p53, and amplification of
      myc gene. These results suggest that renal PDNEC has a different genetic
      background to renal clear cell carcinoma, mainly characterized by the loss of the
      short arm of chromosome 3. Conversely, genetic alterations seem to resemble those
      of type 2 papillary renal cell carcinoma. The review of the literature
      demonstrated that PDNECs are associated with poor prognosis and that parenchymal
      tumors show some differences from those arising in the pelvis, in that
      parenchymal tumors are purely neuroendocrine while pelvic tumors are mostly mixed
      neuroendocrine-exocrine neoplasms.

PMID- 19096941
TI  - Enrichment of cancer stem cells based on heterogeneity of invasiveness.
AB  - Cancer stem cells (CSCs) have multiple potentials in carcinogenesis and tumor
      progression. However, it is rather difficult to enrich and amplify CSCs either
      from tumor cell lines or even primary tumor tissues. Therefore, establishing new
      methodologies for isolation and enrichment based on the functional properties of
      CSCs is of great importance for studies on CSCs. According to the findings that
      CSCs possess more infiltrative capability as compared with their differentiated
      descendants, we propose a novel strategy based on heterogeneity of cancer cell
      invasiveness for isolation and enrichment of CSCs from committed cancer cell
      population. In addition, we hypothesize that existence of CSCs might be the real
      root of tumor invasion and metastasis.

PMID- 19096944
TI  - Transfer of response codes from choice-response to go/no-go tasks.
AB  - The present study investigated the conditions for observing the Simon effect in
      go/no-go tasks. The Simon effect denotes faster and more accurate responses when
      irrelevant stimulus location and response location correspond than when they do
      not correspond. In four experiments, participants performed both in a choice
      response task (CRT) and in a go/no-go task, and we varied the order and the
      similarity of the tasks. In the CRT, participants pressed a left key to one
      stimulus colour and a right key to another stimulus colour; in the go/no-go task,
      participants pressed one (e.g., left) key to one stimulus colour and refrained
      from responding to the other stimulus colour. As expected, Simon effects were
      consistently observed in the CRT. In contrast, Simon effects in the go/no-go task
      were only observed when it followed the CRT and when the mapping of stimulus
      colours to response locations was preserved between tasks (i.e., in Experiment
      4). Results suggest that transfer of a particular S-R rule including response
      location from the CRT to the go/no-go task was responsible for the Simon effect
      in the latter task. In general, results are consistent with a response
      discrimination account of the Simon effect.

PMID- 19096942
TI  - Identification of RKIP as a differentially tyrosine-phosphorylated protein in
      nasopharyngeal carcinoma and normal nasopharyngeal epithelial tissues by
      phosphoproteomic approach.
AB  - AIMS: To screen for differentially tyrosine-phosphorylated proteins between
      nasopharyngeal carcinoma (NPC) and normal nasopharyngeal epithelial tissues
      (NNET) to provide a basis for elucidate the molecular mechanisms of NPC
      carcinogenesis. METHODS: Two-dimensional (2-D) electrophoresis was applied to
      separate proteins from NPC and NNET, respectively, and 2-D Western blotting was
      performed to detect tyrosine-phosphorylated proteins using antiphosphotyrosine
      antibody. Differentially tyrosine-phosphorylated proteins were identified by
      electrospray ionization-quadrupole time-of-flight MS (ESI-Q-TOF MS). NetPhos
      software was used to predict the tyrosine-phosphorylation sites of the identified
      proteins, and Western blotting was used to detect the tyrosine-phosphorylated
      levels of RKIP in NPC and NNET. RESULTS: Twenty-five differentially tyrosine
      phosphorylated proteins in the two types of tissues were found, 13 of which were
      identified by ESI-Q-TOF MS. Among the 13 identified proteins, tyrosine
      phosphorylated levels of 7 proteins were increased, and those of 6 proteins were
      decreased in NPC compared with NNET. NetPhos software prediction showed that all
      the 13 identified proteins contained tyrosine phosphorylation sites, and the
      differentially tyrosine-phosphorylated level of RKIP in NPC and NNET was
      confirmed. CONCLUSION: The 13 differentially tyrosine-phosphorylated proteins may
      be involved in the development and progression of NPC.

PMID- 19096945
TI  - Effectiveness of subcutaneous injection of sterile water to the lower back for
      pain relief in labor.
AB  - The analgesic efficacy of subcutaneous injection of sterile water compared to
      isotonic saline was investigated in a randomized, controlled study on a total of
      100 women in the active phase of labor and who complained of low back pain. Pain
      perception was rated on a numerical rating scale before and at 10 and 45 minutes
      after the injection. The initial pain score was the same in both groups and pain
      relief was expressed by both groups irrespective of the solution injected, but
      the sterile water group had significantly higher relief scores compared to those
      receiving saline. This was not influenced by maternal age, parity, education,
      body mass index, cervical dilatation at intervention or fetal size, suggesting
      that subcutaneous injection of sterile water to the lower back provides relief
      from back pain during labor.

PMID- 19096946
TI  - NT-proBNP is increased in healthy pregnancies compared to non-pregnant controls.
AB  - Serum concentrations of the amino-terminal pro-B-type natriuretic peptide (NT
      proBNP) may be used to monitor cardiac function during pregnancy but normal
      values are not established for this purpose. Therefore, we investigated NT-proBNP
      in normotensive healthy pregnancies compared to a non-pregnant control group.
      Serum NT-proBNP was measured in 94 normotensive, healthy pregnant women (32+/-6
      years) every five weeks beginning from 12th gestational week (GW) in a
      longitudinal study and compared to a non-pregnant control group of 521 women
      (32+/-7 years). Pooled median serum NT-proBNP levels (25th; 75th percentile) were
      significantly higher in pregnant women compared to non-pregnant women (56 (33;
      95) pg/ml vs. 38 (22; 62) pg/ml (p<0.001)). NT-proBNP increased during pregnancy
      to 73 (51; 124) pg/ml in the 11+6 to 15+6 GW (p<0.001). However, NT-proBNP levels
      from 23+0 GW towards term were comparable to non-pregnant controls. NT-proBNP is
      significantly elevated in healthy pregnancies until mid-pregnancy. As
      preeclampsia and gestational hypertension are associated with increased NT
      proBNP, our results have to be considered in future diagnostic approaches using
      NT-proBNP for these pathologic conditions.

PMID- 19096947
TI  - Stillbirths and infant deaths among migrants in industrialized countries.
AB  - INTRODUCTION: The relation of migration to infant outcomes is unclear. There are
      studies which show that some migrant groups have similar or even better outcomes
      than those from the receiving country. Equally, raised risk of adverse outcomes
      for other migrant groups has been reported. OBJECTIVE: We sought to determine (1)
      if migrants in western industrialized countries have consistently higher risks of
      stillbirth, neonatal mortality, or infant mortality, (2) if there are migrant sub
      groups at potentially higher risk, and (3) what might be the explanations for any
      risk differences found. DESIGN AND SETTING: Systematic review of the literature
      on perinatal health outcomes among migrants in western industrialized countries.
      METHODS AND MAIN OUTCOME MEASURES: Drawing on a larger systematic review of
      perinatal outcomes and migration, we reviewed studies including mortality
      outcomes (stillbirths and infant deaths). RESULTS: Eligible studies gave
      conflicting results. Half (53%) reported worse mortality outcomes, one third
      (35%) reported no differences and a few (13%) reported better outcomes for births
      to migrants compared to the receiving country population. Refugees were the most
      vulnerable group. For non-refugees, non-European migrants in Europe and foreign
      born blacks in the United States had the highest excess mortality. In general,
      adjustment of background factors did not explain the increased mortality rate
      among migrants. Regarding causes of death, higher preterm birth rates explained
      the increased mortality figures among some migrant groups. The increased
      mortality from congenital anomalies may be related to restricted access to
      screening, but also to differing attitudes to screening and termination of
      pregnancy. CONCLUSIONS: Mortality risk among babies born to migrants is not
      consistently higher, but appears to be greatest among refugees, non-European
      migrants to Europe, and foreign-born blacks in the US. To understand this
      variation better, more information is needed about migrant background, such as
      length of time in receiving country and receiving country language fluency.
      Additional data on demographic, health care, biological, medical, and
      socioeconomic risk factors should be gathered and analyzed in greater detail.

PMID- 19096948
TI  - Cognitive function and quality of life after surgery for early breast cancer in
      North Jutland, Denmark.
AB  - OBJECTIVE: The aim of this study was to assess cognitive function, quality of
      life, and psychological distress after surgery for early breast cancer but before
      initiation of adjuvant treatment. MATERIAL AND METHODS: We performed a population
      based study in the county of North Jutland, Denmark, including 124 women aged
      less than 60 years who had surgery for early breast cancer from 2004 - 2006. They
      were compared with an aged-matched group of 224 women without previous cancer
      selected randomly from the same population. The cognitive function of patients
      and controls was tested using a revised battery from the ISPOCD study. Data were
      collected on quality of life (EORTC QLQ-C30) and psychological distress (POMS).
      RESULT: The neuropsychological tests did not reveal significant differences
      between patients and controls. Compared to the control group, breast cancer
      patients had a significantly 3 - 4 fold increased risk of experiencing cognitive
      impairment. Quality of life and psychological distress were also significantly
      poorer among patients. CONCLUSION: This study demonstrated that women diagnosed
      with breast cancer experience a significant deterioration of their perceived
      cognitive functioning, quality of life and of psychological well being.

PMID- 19096949
TI  - Safety of pregnancy following breast cancer diagnosis.

PMID- 19096950
TI  - Differentiation of primary central nervous system lymphoma and high-grade glioma
      with dynamic susceptibility contrast-enhanced perfusion magnetic resonance
      imaging.
AB  - BACKGROUND: Preoperative differentiation of primary central nervous system
      lymphomas (PCNSLs) from other tumors is important for presurgical staging,
      intraoperative management, and postoperative treatment. Dynamic susceptibility
      contrast-enhanced perfusion magnetic resonance imaging (DSC perfusion MRI) can
      provide in vivo assessment of the microvasculature in intracranial mass lesions.
      PURPOSE: To determine the utility of DSC perfusion MRI in the differentiation of
      PCNSLs and high-grade gliomas, as well as their pathological and physiological
      differences. MATERIAL AND METHODS: Nine patients with pathologically proven
      PCNSLs and 11 patients with high-grade gliomas were examined using a 1.5 T MRI
      scanner. DSC perfusion MRI was performed by gradient-echo echo-planar imaging (GE
      EPI). The maximum rCBV ratio, the signal intensity-time curves, and the
      percentage of signal intensity recovery were obtained. The maximum relative
      cerebral blood volume (rCBV) ratio and the percentage of signal intensity
      recovery of PCNSLs were compared with those of high-grade gliomas by using
      Student's t test. Microvessel density (MVD) was evaluated using
      immunohistochemical staining of surgical specimens with anti-CD34, and MVDs of
      the two tumor groups were compared by using Student's t test. RESULTS: The
      maximum rCBV ratio of primary intracranial lymphomas was 1.72+/-0.59, while that
      of high-grade gliomas was 4.86+/-2.18. PCNSLs tended to have relatively low
      perfusion compared to high-grade gliomas (P=0.001), and the MVD labeled by anti
      CD34 of PCNSLs was much lower than that of gliomas (P<0.001). The signal
      intensity-time curve of primary intracranial lymphomas was different from that of
      high-grade gliomas. The percentage of signal intensity recovery was significantly
      greater in PCNSLs compared with that of high-grade gliomas (P<0.001). CONCLUSION:
      The difference in DSC perfusion MRI characteristics between PCNSLs and high-grade
      gliomas is determined by their different vascularities and different patterns of
      contrast agent leakage. This difference may be helpful in the diagnosis and
      preoperative differentiation between PCNSLs and high-grade gliomas, which
      sometimes may have similar conventional MR imaging appearance.

PMID- 19096951
TI  - Association of lumbar arterial stenosis with low back symptoms: a cross-sectional
      study using two-dimensional time-of-flight magnetic resonance angiography.
AB  - BACKGROUND: Recent studies indicate that diminished blood flow may cause low back
      symptoms and intervertebral disc degeneration. PURPOSE: To explore the
      association between lumbar arterial stenosis as detected by two-dimensional time
      of-flight magnetic resonance angiography (2D TOF-MRA) and lumbar pain symptoms in
      an occupational cohort of middle-aged Finnish males. MATERIAL AND METHODS: 228
      male subjects aged 36 to 55 years (mean 47 years) were imaged with 2D TOF-MRA.
      Additionally, 20 randomly selected subjects were scanned with contrast-enhanced
      MRA (ceMRA). In each subject, the first (L1) to fourth (L4) segmental lumbar
      arteries were evaluated for lumbar artery stenosis using a dichotomic scale. One
      subject was excluded because of poor image quality, reducing the study population
      to 227 subjects. Logistic regression analysis was used to evaluate the
      association between arterial stenosis in 2D TOF-MRA and low back pain and
      sciatica symptoms (intensity, duration, frequency). RESULTS: Comparing 2D TOF-MRA
      and ceMRA images, the kappa value (95% confidence interval) was 0.52 (0.31-0.73).
      The intraobserver reliability kappa value for 2D TOF-MRA was 0.85 (0.77-0.92),
      and interobserver kappa was 0.57 (0.49-0.65). The sensitivity of 2D TOF-MRA in
      detecting stenosis was 0.58, the accuracy 0.89, and the specificity 0.94. In 97
      (43%) subjects all arteries were normal, whereas 130 (57%) had at least one
      stenosed artery. The left L4 artery was most often affected. The degree of
      arterial stenosis was associated with intensity of low back and sciatic pain, and
      sciatica pain duration during the past 3 months. CONCLUSION: 2D TOF-MRA is an
      acceptable imaging method for arterial stenosis compared to ceMRA. Arterial
      stenosis was associated with subjective pain symptoms, indicating a role of
      decreased nutrition in spinal disorders.

PMID- 19096952
TI  - Respiratory-gated positron emission tomography and breath-hold computed
      tomography coupling to reduce the influence of respiratory motion: methodology
      and feasibility.
AB  - BACKGROUND: Respiratory motion causes uptake in positron emission tomography
      (PET) images of chest and abdominal structures to be blurred and reduced in
      intensity. PURPOSE: To compare two respiratory-gated PET binning methods (based
      on frequency and amplitude analyses of the respiratory signal) and to propose a
      "BH-based" method based on an additional breath-hold computed tomography (CT)
      acquisition. MATERIAL AND METHODS: Respiratory-gated PET consists in list-mode
      (LM) acquisition with simultaneous respiratory signal recording. A phantom study
      featured rectilinear movement of a 0.5-ml sphere filled with (18)F
      fluorodeoxyglucose ((18)F-FDG) solution, placed in a radioactive background
      (sphere-to-background contrast 6:1). Two patients were also examined. Three
      figures of merit were calculated: the target-to-background ratio profile (TBRP)
      in the axial direction through the uptake (i.e., the sphere or lesion), full
      width-at-half-maximum (FWHM) values, and maximized standard uptake values
      (SUV(max)). RESULTS: In the phantom study, the peak TBRP was 0.9 for non-gated
      volume, 1.83 for BH-based volume, and varied between 1.13 and 1.73 for Freq-based
      volumes and between 1.34 and 1.66 for Amp-based volumes. A reference volume (REF
      static) was also acquired for the phantom (in a static, "expiratory" state), with
      a peak TBRP at 1.88. TBRPs were computed for patient data, with higher peak
      values for all gated volumes than for non-gated volumes. CONCLUSION: Respiratory
      gated PET acquisition reduces the blurring effect and increases image contrast.
      However, Freq-based and Amp-based volumes are still influenced by inappropriate
      attenuation correction and misregistration of mobile lesions on CT images. The
      proposed BH-based method both reduces motion artifacts and improves PET-CT
      registration.

PMID- 19096953
TI  - Effect of radiation monitoring method and formula differences on estimated
      physician dose during percutaneous coronary intervention.
AB  - BACKGROUND: Currently, one or two dosimeters are used to monitor radiation
      exposure in most cardiac laboratories. In addition, several different formulas
      are used to convert exposure data into an effective dose (ED). PURPOSE: To
      clarify the effect of monitoring methods and formula selection on the estimated
      ED for physicians during percutaneous coronary interventions (PCIs). MATERIAL AND
      METHODS: The ED of physicians during cardiac catheterization was determined using
      an optically stimulated luminescence dosimeter (Luxel badge). Two Luxel badges
      were worn: one beneath a personal lead apron (0.35-mm lead equivalent) at the
      chest and one outside of the apron at the neck. RESULTS: The difference in the
      average ED of seven physicians was approximately fivefold (range 1.13-5.43
      mSv/year) using the six different formulas in the clinical evaluation. The
      estimated physician ED differed markedly according to both the monitoring method
      and formula selected. CONCLUSION: ED estimation is dependent on both the
      monitoring method and the formula used. Therefore, it is important that
      comparisons among laboratories are based on the same monitoring method and same
      formula for calculating the ED.

PMID- 19096954
TI  - Organ doses and effective doses in pediatric radiography: patient-dose survey in
      Finland.
AB  - BACKGROUND: Use of the effective dose in diagnostic radiology permits the
      radiation exposure of diverse diagnostic procedures to be quantified. Fundamental
      knowledge of patient doses enhances the implementation of the "as low as
      reasonably achievable" (ALARA) principle. PURPOSE: To provide comparative
      information on pediatric examination protocols and patient doses in skull, sinus,
      chest, abdominal, and pelvic radiography examinations. MATERIAL AND METHODS: 24
      Finnish hospitals were asked to register pediatric examination data, including
      patient information and examination parameters and specifications. The total
      number of examinations in the study was 1916 (1426 chest, 228 sinus, 96
      abdominal, 94 skull, and 72 pelvic examinations). Entrance surface dose (ESD) and
      dose-area products (DAP) were calculated retrospectively or DAP meters were used.
      Organ doses and effective doses were determined using a Monte Carlo program
      (PCXMC). RESULTS: There was considerable variation in examination protocols
      between different hospitals, indicating large variations in patient doses. Mean
      effective doses of different age groups ranged from 5 microSv to 14 microSv in
      skull and sinus examinations, from 25 microSv to 483 microSv in abdominal
      examinations, and from 6 microSv to 48 microSv in chest examinations. CONCLUSION:
      In chest and sinus examinations, the amount of data was extensive, allowing
      national pediatric diagnostic reference levels to be defined. Parameter selection
      in pediatric examination protocols should be harmonized in order to reduce
      patient doses and improve optimization.

PMID- 19096955
TI  - Reproducibility of dynamic computed tomography brain perfusion measurements in
      patients with significant carotid artery stenosis.
AB  - BACKGROUND: Perfusion computed tomography (PCT) determination is a minimally
      invasive and widely available technique for brain blood flow assessment, but its
      application may be restricted by large variation of results. PURPOSE: To
      determine the intraobserver, interobserver, and interexamination variability of
      brain PCT absolute measurements in patients with significant carotid artery
      stenosis (CAS), and to evaluate the effect of the use of relative perfusion
      values on PCT reproducibility. MATERIAL AND METHODS: PCT imaging was completed in
      61 patients before endarterectomy, and in 38 of these within 4 weeks after
      treatment. Cerebral blood flow (CBF), cerebral blood volume (CBV), time to peak
      (TTP), and peak enhancement intensity (PEI) were calculated with the maximum
      slope method. Interexamination variability was evaluated based on perfusion of
      hemisphere contralateral to the treated CAS, from repeated examinations.
      Interobserver and intraobserver variability were established for the untreated
      side, based on pretreatment examination. RESULTS: Interobserver and intraobserver
      variability were highest for CBF measurement (28.8% and 32.5%, respectively), and
      interexamination variability was the highest for CBV (24.1%). Intraobserver and
      interobserver variability were higher for absolute perfusion values compared with
      their respective ratios for CBF and TTP. The only statistically significant
      difference between perfusion values measured by two observers was for CBF (mean
      78.3 vs. 67.5 ml/100 g/min). The interexamination variability of TTP (12.1%) was
      significantly lower than the variability of other absolute perfusion measures,
      and the interexamination variability of ratios was significantly lower than
      absolute values for all the parameters. CONCLUSION: In longitudinal studies of
      patients with chronic cerebral ischemia, PCT ratios and either TTP or CBV are
      more suitable measures than absolute CBF values, because of their considerably
      lower inter- and intraobserver variability. Differences in CBF between two
      examinations as high as 30% may be considered as significant in such patients.

PMID- 19096956
TI  - Value of perineural edema/inflammation detected by fat saturation sequences in
      lumbar magnetic resonance imaging of patients with unilateral sciatica.
AB  - BACKGROUND: Routine lumbar spine magnetic resonance imaging (MRI) may not show
      any evidence of the cause of sciatica in some cases. The relationship between
      nerve root compression detected on lumbar MRI and sciatica is also sometimes
      uncertain. PURPOSE: To ascertain whether axial (and, when necessary, sagittal and
      coronal) short-tau inversion recovery or fat-saturated T2-weighted MRI findings
      can be used to study the level of sciatica in patients with a non-yielding
      routine MRI examination. MATERIAL AND METHODS: A total of 215 patients with
      unilateral sciatica underwent MRI. All patients were asked to complete pain
      drawing forms describing their pain dermatomal distributions. Perineural
      edema/inflammation corresponding to the pain location indicated by the pain
      drawings was sought on short-tau inversion recovery or fat-saturated T2-weighted
      images. RESULTS: Routine MRI findings revealed that 110 of the 215 patients had
      nerve root compromise related to the patients' symptoms. Routine MRI could not
      ascertain the cause of these symptoms in the remaining 105 patients. In 31
      (29.5%) of these 105 patients, short-tau inversion recovery or fat-saturated T2
      weighted magnetic resonance images revealed perineural edema/inflammation
      surrounding the nerve roots related to the pain locations indicated in the pain
      drawings. CONCLUSION: Axial (and, when required, sagittal and coronal) short-tau
      inversion recovery or fat-saturated T2-weighted magnetic resonance images may be
      helpful for revealing additional findings in cases of unexplained sciatica in
      standard magnetic resonance imaging. However, the value of this imaging may be
      not great enough to justify routine use of these additional sequences to study
      the level of sciatica.

PMID- 19096957
TI  - Aortic dissection with left atrial compression: an unusual cause of
      breathlessness.

PMID- 19096958
TI  - Editorial. Happy new year!

PMID- 19096960
TI  - MicroRNAs as biomarkers and therapeutic drugs in human cancer.
AB  - MicroRNAs (miRNAs) are evolutionarily conserved, endogenous, noncoding small RNAs
      that act as post-transcriptional gene regulators. Experimental evidence has shown
      that miRNAs can play roles as oncogenes or tumor suppressor genes, suggesting
      their contribution to cancer development and progression. Expression profiles of
      human miRNAs demonstrated that many miRNAs are deregulated in cancers and are
      differentially expressed in normal tissues and cancers. Therefore, miRNA
      profiling is used to create signatures for a variety of cancers, indicating that
      the profile will help further establish molecular diagnosis, prognosis and
      therapy using miRNAs. This paper introduces the aberrant expression of miRNAs in
      human cancer, and discusses the potential of these miRNAs as biomarkers and
      targets/molecules for molecular therapy.

PMID- 19096959
TI  - The anxiety disorder spectrum: fear imagery, physiological reactivity, and
      differential diagnosis.
AB  - This review considers recent research assessing psychophysiological reactivity to
      fear imagery in anxiety disorder patients. As in animal subjects, fear cues
      prompt in humans a state of defensive motivation in which autonomic and somatic
      survival reflexes are markedly enhanced. Thus, a startle stimulus presented in a
      fear context yields a stronger (potentiated) reflex, providing a quantitative
      measure of fearful arousal. This fear potentiation is further exaggerated in
      specific or social phobia individuals when viewing pictures or imagining the
      phobic object. Paradoxically, fear imagery studies with more severe anxiety
      disorder patients--panic disorder with agoraphobia, generalized anxiety disorder,
      or anxious patients with comorbid depression--show a blunted, less robust fear
      potentiated response. Furthermore, this reflex blunting appears to systematically
      be more pronounced over the anxiety disorder spectrum, coincident with lengthier
      chronicity, worsening clinician-based judgments of severity and prognosis, and
      increased questionnaire-based indices of negative affectivity, suggesting that
      normal defensive reactivity may be compromised by an experience of long-term
      stress.

PMID- 19096961
TI  - Effect of intensive lifestyle intervention on C-reactive protein in subjects with
      impaired glucose tolerance and obesity. Results from a randomized controlled
      trial with 5-year follow-up.
AB  - C-reactive protein (CRP) is a marker of metabolic and cardiovascular disease. To
      study the effects of lifestyle on CRP in a high-risk population we conducted a
      randomized controlled trial on 200 obese subjects (BMI > 27 kg m(-2)) with
      impaired glucose tolerance recruited from primary care settings. They were
      randomized to either a 1-month stay at a wellness centre focusing on diet,
      exercise and stress management (intervention group) or 30-60 min of oral and
      written information on lifestyle intervention (control group). A significant
      reduction of CRP was observed after 1 month and 1 year in the intervention group.
      They reduced their CRP levels more than the control group 1 year after
      intervention (p=0.004). In conclusion lifestyle intervention can decrease CRP in
      obese individuals with impaired glucose tolerance for up to 1 year. Further
      research is needed to evaluate whether the CRP level reduction translates into a
      decreased risk for cardiovascular morbidity.

PMID- 19096962
TI  - HIF-1alpha mRNA gene expression levels in improved diagnosis of early stages of
      prostate cancer.
AB  - OBJECTIVES: Several clinical studies have indicated that the rates of invasive
      growth and metastatic disease in cancer depend on the degree of hypoxia, which is
      mediated by hypoxia-inducible factor 1 alpha (HIF-1alpha). To determine its
      potential role as a marker for prostate cancer (CaP) diagnosis, HIF-1alpha mRNA
      levels were measured in blood samples of patients diagnosed with different stages
      of prostatic disease. METHODS: HIF-1alpha mRNA levels were measured by
      quantitative reverse transcriptase-polymerase chain reaction (qRT-PCR) and
      correlated with accurate clinicopathological data. Quantitative data were
      compared with serum prostate-specific antigen (PSA) measurements to determine
      variations in the accuracy of the CaP diagnosis. RESULTS: HIF-1alpha mRNA levels
      were significantly upregulated in patients with localized CaP (LocCaP; n=63;
      p<0.0001), compared with patients with no evidence of malignancy (NEOM) and
      benign prostatic hyperplasia (BPH) (n=35 for both patient groups combined).
      Receiver operator characteristic (ROC) curve analysis demonstrated that HIF
      1alpha specificity for the NEOM/BPH diagnosis was 88.6%. Sensitivity for LocCaP
      was 74.6% with an overall diagnostic efficiency of 79.6%. Specificity of the NEOM
      diagnosis at PSA levels of 4.0 ng ml(-1) was 28.6% and sensitivity of the LocCap
      diagnosis was 65.1%, demonstrating a reduced overall diagnostic efficiency,
      compared with that given by HIF-1alpha measurements, of 52.0%. Levels of HIF
      1alpha in patients with metastatic CaP (MetCaP; n=27)) were similar to those in
      the NEOM/BPH group. CONCLUSIONS: HIF-1alpha is upregulated early in CaP
      development with subsequent downregulation at later metastatic stages. This study
      demonstrates increased accuracy of early-stage disease diagnosis using HIF-1alpha
      qRT-PCR compared with serum PSA measurements. HIF-1alpha may therefore be a
      useful adjunct, together with other diagnostic markers used in relative qRT-PCR
      and current diagnostic techniques (including serum PSA and PSA velocity) to
      minimize unnecessary biopsies indicated by elevated serum PSA levels alone.

PMID- 19096963
TI  - The evolving systemic and local biomarker milieu at different stages of disease
      progression in rat collagen-induced arthritis.
AB  - Rats with collagen-induced arthritis (CIA) were necropsied on 14 occasions from 4
      days after induction to 27 days after disease onset to evaluate the kinetics of
      local (joint protein extracts) and systemic (serum) levels of inflammatory and
      pro-erosive factors. Systemic increases in alpha1 acid glycoprotein and KC/GRO
      together with systemic and local enrichment of interleukin (IL)-1beta, IL-6,
      CCL2, transforming growth factor (TGF)-beta and elevated IL-1alpha and IL-18 in
      joint extracts preceded the onset of clinical disease. Systemic upregulation of
      IL-1beta, IL-6, TGF-beta CCL2, RANKL and prostaglandin E(2) (PGE(2)) during acute
      and/or chronic CIA coincided with systemic leukocytosis and a CD4+ T-cell
      increase in blood and spleen. In contrast, progression of joint erosions during
      clinical CIA was associated with intra-articular increases in IL-1alpha/beta, IL
      6, IL-18, CCL2, KC/GRO and RANKL, and a dramatic decline in osteoprotegerin
      (OPG). These data indicate that systemic and local events in inflammatory
      arthritis can be discrete processes, driven by multiple cellular and humoral
      mediators with distinct temporospatial profiles.

PMID- 19096964
TI  - Serum interleukin-1beta as a marker for differentiation of asthma and chronic
      obstructive pulmonary disease.
AB  - Asthma and chronic obstructive pulmonary disease (COPD) are diseases of airway
      inflammation with clinical and physiological similarities, making their
      differentiation difficult. Airway inflammatory changes are associated with
      systemic changes. However, no serum marker is known for their differentiation.
      Therefore, serum interleukin (IL)-1beta levels were determined. Out of a total of
      1023 patients screened, we included in the study ten patients each with atopic
      asthma, non-atopic asthma and COPD and ten healthy subjects. Skin prick tests
      with 14 inhalant allergens were performed on each patient. Blood was collected in
      the symptomatic and asymptomatic phases of the diseases and serum IL-1beta and
      IgE levels were determined. Our results showed that in the symptomatic phase in
      asthmatics, serum IL-1beta levels were higher (P<0.05) than in patients with
      COPD. Serum IgE levels were higher (P<0.05) in atopic asthmatics than in non
      atopic asthmatics and in COPD patients. We conclude that serum IL-1beta level
      determination during the symptomatic phase of the diseases may help to
      differentiate asthmatics from patients with COPD. Serum IgE levels may
      differentiate atopic asthmatics from non-atopic asthmatics and COPD patients.

PMID- 19096965
TI  - Activity and function in lung injuries due to sulphur mustard.
AB  - AIM: Pulmonary complications are known to occur in over half the patients exposed
      to sulphur mustard. Many studies have focused on the clinical complications,
      often ignoring the pathogenesis of sulphur mustard. Also, the reasons for the
      variable severity of lung injuries caused by sulphur mustard are unclear. Hence,
      the current study was performed to evaluate the correlation between superoxide
      dismutase (SOD) and catalase (CAT) activity and pulmonary function in patients
      exposed to sulphur mustard. METHODS: Our study was a comparative cross-sectional
      survey. Two hundred and fifty incident survivors were selected from the Sardasht
      population who were exposed to sulphur mustard in 1987. A control group from non
      exposed civilians was also selected. We used a pulmonary function test, and SOD
      and CAT activity was measured in these groups. RESULTS: The mean SOD activity in
      the healthy control group (70.5+/-10.8 U ml(-1)) was higher than in the moderate
      to-severe group (67.0+/-6.1 U ml(-1)) (p <0.001, one-tail ANOVA, least
      significant difference (LSD) post hoc). The mean activity in the mild group
      (72.5+/-6.9 U ml(-1)) was no higher than in the healthy control group (70.5+/
      10.8 U ml(-1)) (p=0.095 one-tail ANOVA, LSD post hoc). The mean CAT activity in
      the healthy control group (4.9+/-1.5 U ml(-1)) was lower than in the moderate-to
      severe group (8.0+/-1.8 U ml(-1)) (p <0.001, one-tail ANOVA, LSD post hoc) and in
      the mild group (7.5+/-1.5 U ml(-1)) (p=0.012 one-tail ANOVA, LSD post hoc).
      CONCLUSION: According to our findings, it is reasonable to hypothesize that re
      establishment of the activation-inactivation or oxidant-antioxidant balance in
      favour of the activation and antioxidant balances would be useful as a
      therapeutic strategy to suppress pathological mechanisms underlying lung
      injuries.

PMID- 19096966
TI  - Stain and dye stability over a 30-year period: a comparison of certified dye
      powders by the Biological Stain Commission.
AB  - The Biological Stain Commission (BSC) Assay Laboratory has received numerous
      inquiries during the past several years regarding the long-term stability of
      stain and dye powders, particularly since packaging requirements call for
      expiration dates on reagents. We have conducted a study to examine the long-term
      stability of selected dye powders. We used the standard procedures of the BSC for
      testing biological stains for certification to give an indication of the long
      term chemical stability as well as staining performance of the dye powders. An
      earlier study by Emmel and Stotz examined the stability of various dye powders
      after a five-year storage period. The present study is a follow-up project
      covering the same dyes after storage for 30 years. The dye samples chosen for the
      study are the same samples used in the five-year storage period study and give
      comparative results for all three time periods. The results of this study affirm
      the generally held speculation that dye powders are stable for many years and
      thus have a substantial shelf-life.

PMID- 19096967
TI  - Screening for traumatic brain injury.
AB  - PRIMARY OBJECTIVE: The researchers implemented a traumatic brain injury (TBI)
      screening procedure in settings likely to have relatively frequent contacts with
      survivors to better document TBI occurrence among populations at high-risk for
      under-identification. METHODS AND PROCEDURES: Professionals from four service
      agencies administered a TBI screening protocol to all incoming clients over a 6
      month period. MAIN OUTCOMES AND RESULTS: Of the 1999 protocols collected, 531
      (26.56%) were positive for a possible history of TBI of sufficient severity to
      impact quality of life. Memory challenges were the most common chronic complaint
      among individuals with positive screen results, with struggles with headaches,
      depression, concentration and anxiety also commonly reported. CONCLUSIONS: Large
      numbers of people seeking vocational rehabilitation, domestic abuse, homeless
      shelter or mental health services may experience persistent challenges stemming
      from unidentified TBIs. Identifying these individuals and the source of their
      challenges is important when developing intervention and supportive services.
      Using a TBI screening tool is one means of facilitating this identification
      process.

PMID- 19096968
TI  - Determinants of health-related quality of life 22 years after hospitalization for
      traumatic brain injury.
AB  - PRIMARY OBJECTIVE: To assess health-related quality of life (HRQoL) and its
      determinants in a cohort who had sustained a traumatic brain injury 22 years
      earlier. RESEARCH DESIGN: Cohort study with a postal follow-up survey. METHODS
      AND PROCEDURES: Two hundred and fifty-nine individuals with traumatic brain
      injury responded to the Short Form-36 (SF-36) and General Health Questionnaire-30
      (GHQ-30) questionnaires. SF-36 scores were compared with a general population
      sample (n = 6800). In multiple linear regression analysis determinants of
      physical and mental component summary scores (PCS, MCS) of SF-36 and the GHQ-30
      total score were assessed. MAIN OUTCOMES AND RESULTS: Except on the physical
      functioning scale, SF-36 scores were lower in the traumatic brain injury cohort
      than in the general population, after adjusting for age, sex and education. In
      multiple linear regression analysis, reported psychiatric disease and headache
      >or=1 day per month were associated with impaired MCS and GHQ-30 total scores.
      Age, severe headache 3 months after the injury, previous sick leave, lung disease
      and heart disease were associated with PCS. No injury variable was associated
      with HRQoL. CONCLUSIONS: Headache 3 months after traumatic brain injury and later
      comorbidity were associated with HRQoL 22 years after traumatic brain injury, but
      there was no association of HRQoL with injury data.

PMID- 19096969
TI  - Skull fracture, with or without clinical signs, in mTBI is an independent risk
      marker for neurosurgically relevant intracranial lesion: a cohort study.
AB  - PRIMARY OBJECTIVE: To explore the possibility of identifying skull fracture, with
      or without clinical signs, as a predictor of positive CT scans in mild traumatic
      brain injury (mTBI). RESEARCH DESIGN: Prospective cohort study, matched 1:1 for
      five potential confounding variables (age, sex, symptoms, mechanism of injury and
      extracranial trauma severity). METHODS AND PROCEDURES: The study was performed on
      patients with mTBI (Glasgow Coma Scale 15-14), with or without radiologically
      demonstrated skull fracture. The cohort with skull fracture included 155 patients
      selected from a sample of 5097 mTBI patients treated during 1998 at the Critical
      Care and Emergency Department of the Trauma Centre. The cohort without skull
      fracture was prospectively recruited from patients with mTBI treated in the same
      department from 2002-2005. MAIN OUTCOMES AND RESULTS: The percentage of patients
      with intracranial lesion (IL) was significantly higher in mTBI patients with
      skull fracture than in those without. The risk of requiring neurosurgery was 5
      fold higher when skull fracture was present. Of mTBI patients with skull fracture
      and IL, 63.2% showed no clinical signs of bone injury. CONCLUSIONS: Skull
      fracture, with or without clinical signs, in mTBI patients is associated with an
      increased risk of neurosurgically-relevant intracranial lesion.

PMID- 19096970
TI  - Ecological validity of the neuropsychological assessment battery screening module
      in post-acute brain injury rehabilitation.
AB  - PRIMARY OBJECTIVE: To assess the ecological validity of the Screening Module of
      the Neuropsychological Assessment Battery (NAB-SM) using the Functional
      Independence Measure (FIM). METHOD: Seventy individuals with moderate-to-severe
      traumatic brain injury at a residential post-acute rehabilitation facility were
      administered the FIM instrument and the NAB-SM upon admission. Hierarchical
      regression analysis was used to examine the relationship between the variables
      from these two assessment measures. RESULTS: Hierarchical models revealed that
      (1) the NAB-SM Total score was significantly associated with the FIM instrument
      Total score as well as the Motor and Cognition sub-scale scores, above and beyond
      the contribution of demographic variables, (2) the NAB-SM Language, Memory and
      Spatial domain scores were significantly associated with of the FIM instrument
      Cognition sub-scale score and (3) the NAB-SM Spatial domain score was
      significantly associated with of the FIM instrument Total and Motor sub-scale
      scores. CONCLUSIONS: The current findings support previous research and provide
      strong evidence for the ecological validity of the NAB-SM with regard to
      functional abilities as assessed by the FIM instrument.

PMID- 19096971
TI  - Injury severity and disability in the selection of next level of care following
      acute medical treatment for traumatic brain injury.
AB  - PRIMARY OBJECTIVE: To evaluate the association of demographic factors, post
      traumatic amnesia (PTA) and a standardized measure of ability limitations with
      clinical decisions for Next Level of Care following acute hospital treatment for
      moderate-severe traumatic brain injury (TBI). RESEARCH DESIGN: A TBI Clinical
      Nurse specialist recorded PTA for 212 individuals and rated 159 on the Ability
      and Adjustment Indices of the Mayo-Portland Adaptability Inventory (MPAI-4) for
      comparison with clinical decisions. MAIN OUTCOMES AND RESULTS: Multivariate
      logistic regression analyses revealed that independent ratings on the MPAI-4
      Ability Index and PTA were associated with the clinical decision to admit to
      Inpatient Rehabilitation vs discharge to Home in 92.7% of the sample; ratings on
      the Ability Index alone were associated with this decision in 92.2% of cases. Age
      over 65 was the only variable associated with discharge to a Skilled Nursing
      Facility, correctly predicting this decision in 64% of cases. CONCLUSIONS: Use of
      a standardized measure of ability limitations appears feasible to provide
      supportive documentation and potentially improve the consistency of decision
      making in recommending Inpatient Rehabilitation vs discharge to Home. Although
      age is a significant factor in the decision to discharge to a Skilled Nursing
      Facility, this decision appears complex and merits further study.

PMID- 19096972
TI  - Treatment paths and costs for young adults with acquired brain injury in the
      United Kingdom.
AB  - PRIMARY OBJECTIVES: To identify the health and social care services used by young
      adults aged 18-25 years with acquired brain injury (ABI) and the costs of these
      supports. RESEARCH METHODS: A review of existing literature and databases and
      contact with academics and stakeholders working with people with ABI. MAIN
      OUTCOMES AND RESULTS: The likely care pathways of young adults with ABI were
      mapped over a notional 1-year period after presentation at hospital accident and
      emergency departments. Most young adults with ABI will use minimal health and
      social care support following injury but those with subsequent disabilities may
      cost the health and social care budget in excess of pound47.2 million per year.
      CONCLUSION: Lack of available data mean the service use and cost estimates draw
      from a range of sources. However, the costs may under-estimate the true impact on
      budgets as incidence rates may be higher than identified and conservative values
      were selected for unit costs. The model estimates the cost of treatment and
      support as provided today, but high levels of unmet need remain.

PMID- 19096973
TI  - Evidence for chronically elevated serum protein oxidation in systemic lupus
      erythematosus patients.
AB  - Serum protein oxidation levels in people with the autoimmune disease systemic
      lupus erythematosus (SLE) have previously been shown to (a) be elevated at a
      single time point and (b) correlate with disease activity. This study
      investigates whether this elevation is a chronic phenomenon, by analysis of
      multiple serum samples collected from 21 SLE patients and nine controls over a
      period of up to 38 months. Protein thiols were chronically decreased in SLE
      patients with stable or variable disease activity compared to controls, whilst
      protein-bound carbonyls and glycine were chronically increased. 2D-gel analysis
      of carbonyl distribution showed albumin and immunoglobulins to be particularly
      affected. In SLE patients with stable disease activity, higher long-term protein
      oxidation correlated with higher long-term disease activity. SLE patients with
      variable disease activity exhibited varying correlations between protein
      oxidation and disease activity markers. These results further support a role for
      oxidative stress in the pathogenesis of SLE.

PMID- 19096975
TI  - Integrative action of receptor mosaics: relevance of receptor topology and
      allosteric modulators.
AB  - After a definition of the receptor mosaic (RM, high order heteromer or homomer)
      concept, this study analyzes some relevant theoretical aspects related to
      receptor-receptor interactions (RRIs). In particular, the possible influence of
      the plasma membrane microdomain on RM integrative functions are discussed.
      Furthermore, a possible mathematical approach may identify the RM topologies
      [i.e., the spatial arrangements the receptors (tesserae of the mosaic) can assume
      within the RM assembly]. Finally, data are presented on homocysteine possible
      biasing action on the well-characterized heterodimer/receptor mosaic formed by
      adenosine A2A and dopamine D2 receptors. We discuss how these findings can lead
      to a new possible approach for developing drugs for the treatment of certain
      neuropsychiatric disorders.

PMID- 19096976
TI  - Phospholipase C-activating plasma membrane receptors and calcium signaling in
      immortalized human airway epithelial cells.
AB  - Mechanical clearance of inhaled dust particles and microorganisms is an important
      part of the innate defense mechanisms of mammalian airways. Airway epithelia are
      composed of various cell types with different degrees of cell polarity. Serous
      cells regulate composition and volume of luminal periciliary fluid and mucus.
      Autocrine, paracrine, or neuronal messengers determine the secretory and
      reabsorptive rates of electrolytes and water via cAMP-or inositol
      triphosphate/calcium-mediated intracellular signals. Comparison of the expression
      of calcium-mobilizing receptor types (G protein-coupled-, growth factor-, and
      cytokine receptors) in two types of human immortalized airway epithelial cells
      (S9, 16HBE14o-) revealed that receptor populations were qualitatively and
      quantitatively different in the two cell types. Sustained calcium signals were
      elicited by activation of purinergic receptors in 16HBE14o-cells or muscarinic
      acetylcholine or histamine receptors in S9 cells. These G protein-coupled
      receptors mobilized calcium from intracellular stores and activated capacitative
      calcium influx. The experimental cells may represent different types of original
      airway epithelial cells and seem to be suited as model cells to study cell
      signaling and protein expression during interaction with pathogens or their
      secretory products (e.g., virulence factors).

PMID- 19096977
TI  - Short-term ECG for out of hospital detection of silent atrial fibrillation
      episodes.
AB  - OBJECTIVES: We evaluated a short-term ECG, thumb ECG, for detection of
      asymptomatic atrial fibrillation (AF) episodes. The aim was to evaluate
      registration efficacy, sensitivity, specificity, quality and feasibility in
      patients with special emphasis on asymptomatic AF. DESIGN: One hundred patients
      registered their cardiac rhythm with 12-lead ECG immediately followed by thumb
      ECG. The registrations were compared blindly. A second group of 12 patients, who
      had successfully undergone cardioversion, performed rhythm registration twice
      daily for 30 days. A third group of 606 individuals underwent an AF screening
      procedure. RESULTS: Thumb ECG correctly diagnosed AF (sensitivity) in 96% and
      sinus rhythm (specificity) in 92% compared with 12-lead ECG. In the group of
      cardioverted patients, 466 registrations were validated: 95% had satisfactory
      quality for diagnosis: four patients experienced AF recurrence in which three
      were asymptomatic. In the third group 12 persons were diagnosed with AF, six of
      these had neither symptoms nor a history of AF. CONCLUSIONS: Short-term ECG is
      able to diagnose AF with a high sensitivity, specificity and simple application
      making detection of asymptomatic AF possible for screening purposes.

PMID- 19096979
TI  - A modified canine model of portal hypertension with hypersplenism.
AB  - OBJECTIVE: The aim of this study was to develop and describe an experimental
      canine model of portal hypertension with hypersplenism. MATERIAL AND METHODS:
      Twenty-five dogs were used randomly divided into three groups: group I (control
      group, n = 5), group II (PVS, n = 10) and group III (PVS + SVS, n = 10). Portal
      vein stenosis (PVS) was performed in dogs of group II; in group III dogs the
      model was first prepared by PVS and additional splenic vein stenosis 3 weeks
      later (PVS + SVS). Portal vein pressure (PVP), length of spleen and fluctuation
      of hematocyte counts were measured and recorded at the appointed times. Surgery
      permitted visual verification of portosystemic collateral circulation.
      Histopathological variation of the spleen and condition of the bone marrow
      hyperplasia were examined to confirm the development of hypersplenism. RESULT:
      Both group II and group III developed prehepatic portal hypertension; group III
      also presented satisfactory hypersplenism compared to the control group and group
      II, as documented at surgery and by hematologic and pathologic examination.
      CONCLUSIONS: Based on this study, the modified model of portal hypertension (by
      PVS + SVS) appears appropriate when studying the relationship between
      hypersplenism and hemodynamics in portal hypertension. It is also likely to be
      useful in studying the influence of diseased spleen in the treatment of portal
      hypertension.

PMID- 19096980
TI  - Secondary C-kit mutation is a cause of acquired resistance to imatinib in
      gastrointestinal stromal tumor.
AB  - C-kit gene gain of function mutations are important in the pathogenesis of
      gastrointestinal stromal tumors (GISTs). Imatinib is a selective tyrosine kinase
      inhibitor of KIT and achieves a partial response or stable disease in most
      patients with metastatic GIST, but there is increasing evidence of acquired
      resistance. We report a case of GIST with acquired resistance to imatinib during
      therapy and secondary c-kit mutation besides the primary mutation.

PMID- 19096978
TI  - Increased FOXP3 expression in small-bowel mucosa of children with coeliac disease
      and type I diabetes mellitus.
AB  - OBJECTIVE: To determine whether the expression of FOXP3 is changed in small-bowel
      mucosa in coeliac disease (CD). MATERIAL AND METHODS: The study comprised 52
      patients (mean age 8.01+/-6.14 years) who had undergone small-bowel biopsies. CD
      only was diagnosed in 16 patients, and CD with type I diabetes mellitus (T1D) in
      7. These 23 patients and 4 others without CD had partial or subtotal villous
      atrophy (PVA, SVA). Twenty-five persons without CD had normal mucosa. The
      transcription level of the FOXP3 gene (Hs00203958_m1) was evaluated in biopsy
      samples (small bowel) using TaqMan gene expression assays. FOXP3 protein in
      mucosal cells was evaluated with mouse anti-human FOXP3 antibodies and CD25(+),
      and CD4(+) T cells were evaluated by mouse monoclonal antibodies. RESULTS:
      Expression of FOXP3 mRNA was higher in both PVA and SVA compared to normal mucosa
      (p=0.007). Patients with CD and T1D had higher expression of FOXP3 mRNA than
      patients with CD alone (p=0.02). The number of FOXP3(+) cells in intestinal
      mucosa was higher in patients with CD, especially those with coexisting T1D, than
      in those with normal mucosa (p=0.01). The results of double staining showed that,
      among all positive cells, FOXP3 expression alone was revealed in 25.6% of the
      cells, CD25 positivity in 18% and both markers simultaneously were found in 56.5%
      of lymphocytes (p=0.03). Double staining for CD4 and FOXP3 showed that 87.5% of
      cells were CD4(+), 2.8% were FOXP3(+) and 9.7% of cells simultaneously expressed
      the CD4 and FOXP3 markers. CONCLUSIONS: A more pronounced expression of FOXP3
      mRNA and also the number of FOXP3(+) cells (with simultaneous expression of CD25
      and CD4 markers) were found in the small-bowel biopsy specimens obtained from
      children with CD, particularly those with coexisting T1D, compared with the FOXP3
      expression in normal mucosa.

PMID- 19096981
TI  - Severity of human non-typhoid salmonellosis as a predictor of short- and long
      term mortality.
AB  - We hypothesized that severity of human non-typhoid Salmonella (NTS) infection was
      a marker of 0-30 and 31-365-d mortality. All patients with first-time detection
      of NTS in stool specimens in North Jutland County, Denmark, 1995-2003, were
      categorized into 4 groups. Group 1 was not hospitalized in relation to their NTS
      infection, group 2 was hospitalized without sampling of blood cultures, group 3
      was hospitalized with blood cultures obtained in which pathogenic micro-organisms
      were not detected, and group 4 had blood culture-proven bacteraemia. Among 1764
      NTS patients, 2 of 1082 (0.2%) in group 1, 14 of 344 (4.1%) in group 2, 20 of 248
      (8.1%) in group 3, and 19 of 90 (21.1%) in group 4 died within 365 d. Using group
      2 as reference, age and comorbidity adjusted 0-30-d mortality rate ratios (MRR)
      with 95% confidence intervals (CI) could not be computed for group 1 (no deaths),
      while they were 1.8 (0.6-5.5) for group 3 and 1.4 (0.4-4.9) for group 4. For the
      31-365-d period, MRR (95% CI) were 0.16 (0.03-0.8), 1.6 (0.7-3.7), and 2.5 (1.1
      5.8), respectively, for the 3 groups. Severity of NTS infection was an age- and
      comorbidity-independent short- and long-term prognostic marker of mortality.

PMID- 19096982
TI  - Detection of Rickettsia spp. in Danish ticks (Acari: Ixodes ricinus) using real
      time PCR.
AB  - We examined 192 Ixodes ricinus tick nymphs from Denmark for the presence of
      Rickettsia spp. We used a species-specific real-time PCR; 13.0% of the ticks were
      positive for rickettsial DNA. Only DNA from Rickettsia helvetica was found in the
      ticks.

PMID- 19096983
TI  - Prevalence of cystinuria among elementary schoolchildren in Eskisehir, Turkey.
AB  - OBJECTIVE: Cystinuria is an inherited transport disorder due to defects in
      intestinal and renal transport of cystine and dibasic amino acids. Early
      diagnosis is required for some general and specific treatments because cystinuric
      patients have an increased risk of recurrent urinary stone formation. The
      prevalence of cystinuria varies widely in different countries. The aim of this
      study is to determine the prevalence of cystinuria among schoolchildren in
      Eskisehir, a central Anatolian city in Turkey. MATERIAL AND METHODS: The sodium
      cyanide-nitroprusside spot test was applied to the first morning urine samples
      from 8260 schoolchildren (4087 female, 4173 male, aged between 6 and 12 years).
      Urine and blood amino acids were determined with paper chromatography and special
      cystine-homocystine chromatography were performed if a child had a positive spot
      test result. Urinary cystine levels of two children were measured quantitatively.
      RESULTS: Spot-test results were positive in four students. Increased levels of
      cystine and dibasic amino acids in the urine were determined with paper
      chromatography and cystine spots were also detected with special cystine
      homocystine chromatography for these four students. Urinary cystine levels were
      elevated in two children whose urine could be studied. The prevalence of
      cystinuria in this study was 1:2065. There was no history or symptoms related to
      urolithiasis in these students. CONCLUSION: The prevalence of cystinuria in this
      study is higher than many other countries. Patients in Turkey with urinary stones
      or with symptoms related to urolithiasis must also be investigated for
      cystinuria.

PMID- 19096984
TI  - Investigating the complex nature of the stressor-cortisol association is
      possible: a response to Michaud et al. 2008.

PMID- 19096985
TI  - Cortisol changes associated with stressors in humans. Reply to Schubert.

PMID- 19096986
TI  - Forgiveness and the appraisal-coping process in response to relationship
      conflicts: implications for depressive symptoms.
AB  - The present investigation assessed the mediating role of appraisal-coping
      processes in the relation between forgiveness and depressive symptoms associated
      with intimate relationship conflicts. Study 1 assessed the role of forgiveness in
      the context of a severe relationship stressor, namely women experiencing dating
      abuse, along with the appraisal-coping responses and depressive symptoms
      associated with such a stressor. Study 2 evaluated the function served by
      forgiveness among men and women in response to non-abusive relationship
      stressors, including the dissolution of the relationship, and also assessed the
      relations among forgiveness, appraisal-coping processes, and depressive symptoms.
      Women who encountered dating abuse were less likely to forgive their partners,
      and this was linked to higher levels of depressive symptoms. The relation between
      forgiveness and lower depressive symptoms was partially mediated by lower threat
      appraisals, secondary appraisals of the effectiveness of emotion-focused coping,
      and the reduced endorsements of this coping strategy (Study 1). Appraisal-coping
      processes similarly mediated the relation between forgiveness and depressive
      symptoms among men and women reporting conflict in an ongoing (non-abusive)
      relationship or a relationship break-up (Study 2). It is suggested that the
      relation between forgiveness and diminished distress operates primarily by
      guiding individuals' appraisals of the conflict and by diminishing the reliance
      on emotion-focused coping.

PMID- 19096987
TI  - Longitudinal platelet reactivity to acute psychological stress among older men
      and women.
AB  - Platelet reactivity to acute stress is associated with increased cardiovascular
      disease risk; however, little research exists to provide systematic
      methodological foundations needed to generate strong longitudinal research
      designs. Study objectives were: 1) to evaluate whether markers of platelet
      function increase in response to an acute psychological stress test among older
      adults, 2) to establish whether reactivity remains robust upon repeated
      administration (i.e. three occasions approximately 1 year apart), and 3) to
      evaluate whether two different acute speech stress tasks elicit similar platelet
      responses. The 149 subjects (mean age 71 years) gave a brief impromptu speech on
      one of two randomly assigned topics involving interpersonal conflict. Blood
      samples drawn at baseline and post-speech were assayed using flow cytometry for
      platelet responses on three outcomes (% aggregates, % P-selectin expression, and
      % fibrinogen receptor expression). Three-level hierarchical linear modeling
      analyses revealed significant stress-induced increases in platelet activation on
      all outcomes (p < 0.001). No significant habituation on any measure was found.
      Additional reactivity differences were associated with male gender, history of
      myocardial infarction, and use of aspirin, statins, and antidepressants. The
      results demonstrate that laboratory acute stress tests continued to produce
      robust platelet reactivity on three activation markers among older adults over 3
      years.

PMID- 19096988
TI  - The role of working memory in tactile selective attention.
AB  - Load theory suggests that working memory controls the extent to which irrelevant
      distractors are processed (e.g., Lavie, Hirst, De Fockert, & Viding, 2004).
      However, so far this proposal has only been tested in vision. Here, we examine
      the extent to which tactile selective attention also depends on working memory.
      In Experiment 1, participants focused their attention on continuous target
      vibrations while attempting to ignore pulsed distractor vibrations. In Experiment
      2, targets were always presented to a particular hand, with distractors being
      presented to the other hand. In both experiments, a high (vs. low) load in a
      concurrent working memory task led to greater interference by the tactile
      distractors. These results establish the role of working memory in the control of
      tactile selective attention, demonstrating for the first time that the principles
      of load theory also apply to the tactile modality.

PMID- 19096989
TI  - Selective interference with image retention and generation: evidence for the
      workspace model.
AB  - We address three types of model of the relationship between working memory (WM)
      and long-term memory (LTM): (a) the gateway model, in which WM acts as a gateway
      between perceptual input and LTM; (b) the unitary model, in which WM is seen as
      the currently activated areas of LTM; and (c) the workspace model, in which
      perceptual input activates LTM, and WM acts as a separate workspace for
      processing and temporary retention of these activated traces. Predictions of
      these models were tested, focusing on visuospatial working memory and using dual
      task methodology to combine two main tasks (visual short-term retention and image
      generation) with two interference tasks (irrelevant pictures and spatial
      tapping). The pictures selectively disrupted performance on the generation task,
      whereas the tapping selectively interfered with the retention task. Results are
      consistent with the predictions of the workspace model.

PMID- 19096990
TI  - The contribution of familiarity to recognition memory is a function of test
      format when using similar foils.
AB  - Patient Y.R., who suffered hippocampal damage that disrupted recollection but not
      familiarity, was impaired on a yes/no (YN) object recognition memory test with
      similar foils. However, she was not impaired on a forced-choice corresponding
      (FCC) version of the test that paired targets with corresponding similar foils
      (Holdstock et al., 2002). This dissociation is explained by the Complementary
      Learning Systems (CLS) neural-network model (Norman & O'Reilly, 2003) if
      recollection is impaired but familiarity is preserved. The CLS model also
      predicts that participants relying exclusively on familiarity should be impaired
      on forced-choice noncorresponding (FCNC) tests, where targets are presented with
      foils similar to other targets. The present study tests these predictions for all
      three test formats (YN, FCC, FCNC) in normal participants using two variants of
      the remember/know procedure. As predicted, performance using familiarity alone
      was significantly worse than standard recognition on the YN and FCNC tests, but
      not on the FCC test. Recollection in the form of recall-to-reject was the major
      process driving YN recognition. This adds support to the interpretation of
      patient data, according to which hippocampal damage causes a recollection deficit
      that leads to poor performance on the YN test relative to FCC.

PMID- 19096991
TI  - The different representational frameworks underpinning abstract and concrete
      knowledge: evidence from odd-one-out judgements.
AB  - Recent evidence from neuropsychological investigations of individuals with global
      aphasia and deep or deep-phonological dyslexia suggests that abstract and
      concrete concepts are underpinned by qualitatively different representational
      frameworks. Abstract words are represented primarily by their association to
      other words, whilst concrete words are represented primarily by their taxonomic
      similarity to one another. In the current study, we present the first evidence
      for this association/similarity distinction to be gathered from healthy research
      participants. Using a semantic odd-one-out task, it is shown that normal
      participants identify associative connections more quickly than similarity-based
      connections when processing abstract words, but that the pattern is reversed for
      concrete words. It is also demonstrated that the typical concrete-word advantage
      observed in many cognitive tasks is abolished and even reversed when participants
      have to comprehend the semantic associations between words. The data provide
      converging evidence for the different representational frameworks hypothesis and
      suggest that claims based on information from previous neuropsychological
      investigations can be generalized to normal cognition.

PMID- 19096992
TI  - Delusion of pregnancy associated with antipsychotic induced metabolic syndrome.
AB  - Metabolic syndrome is currently the research topic of several studies. Although
      physical manifestations of metabolic syndrome have been described, the
      psychological and psychiatric impact of metabolic syndrome has not been studied
      to date. We report the first case of antipsychotic-induced metabolic syndrome
      which was associated with development of delusions of pregnancy in a post
      menopausal woman.

PMID- 19096993
TI  - Antifungal triterpene glycosides from the sea cucumber Bohadschia marmorata.
AB  - Four new holostan-type triterpene glycosides, marmoratoside A ( 1), 17 alpha
      hydroxy impatienside A ( 2), marmoratoside B ( 3), 25-acetoxy bivittoside D ( 4),
      together with two known triterpene glycosides, impatienside A ( 5) and
      bivittoside D ( 6), were isolated from the sea cucumber Bohadschia Marmorata
      Jaeger. On the basis of spectroscopic analyses, including two-dimensional NMR
      techniques, and chemical reactions, the structures of the new triterpene
      glycosides were elucidated. Compounds 1, 2, 5, and 6 exhibited significant
      antifungal activity against six strains (0.70 < or = MIC (80) < or = 2.81
      microM).

PMID- 19096994
TI  - EGCG inhibits proliferation of cardiac fibroblasts in rats with cardiac
      hypertrophy.
AB  - This study was carried out in order to investigate the effects of
      epigallocatechin gallate (EGCG) on myocardial fibrosis and cell proliferation in
      cardiac hypertrophy. Cardiac hypertrophy was established in rats by abdominal
      aortic constriction, and EGCG at doses of 25, 50 and 100 mg/kg was administered
      intragastrically for 6 weeks. The results showed that in the rats with cardiac
      hypertrophy, EGCG at 25 - 100 mg/kg dose-dependently reduced heart weight
      indices, decreased atrial natriuretic polypeptide and endothelin levels in
      plasma, but increased nitrite (the oxidative product of NO) levels in the serum
      and in the myocardium. EGCG also reduced the hydroxyproline concentration and
      decreased the proliferating cell nuclear antigen expression in the hypertrophic
      myocardium. EGCG remarkably inhibited pressure overload-induced c-myc increase in
      Western blot analysis. In cultured newborn rat cardiac fibroblasts, treatment
      with EGCG at 12.5 - 200 mg/L for 6 - 48 h decreased cell proliferation induced by
      serum. EGCG at 12.5 - 100 mg/L dose-dependently inhibited cell proliferation and
      DNA synthesis of fibroblasts induced by angiotensin II (Ang II) at 1 mumol/L.
      EGCG also significantly increased nitrite levels in culture medium, and up
      regulated inducible nitric oxide synthase protein expression if compared with the
      Ang II group. The inhibitory effect of EGCG on cell proliferation induced by Ang
      II was partly blocked by pretreatment with N(omega)-nitro- L-arginine methyl
      ester hydrochloride. These results suggest that EGCG inhibits the proliferation
      of cardiac fibroblasts both in vivo and in vitro, thereby preventing myocardial
      fibrosis in cardiac hypertrophy. EGCG might exert its cardiac protective action
      through induction of NO production.

PMID- 19096996
TI  - Application of rotated PCA models to facilitate interpretation of metabolite
      profiles: commercial preparations of St. John's Wort.
AB  - This paper describes the application of orthogonal rotation of models based on
      principal component analysis (PCA) of (1)H nuclear magnetic resonance (NMR)
      spectra and high-performance liquid chromatography-photo diode array detection
      (HPLC-PDA) profiles of natural product mixtures using extracts of antidepressive
      pharmaceutical preparations of St. John's wort as an example. (1)H-NMR
      spectroscopy of complex mixtures is often used in metabolomic, metabonomic and
      metabolite profiling studies for assessment of sample composition. Interpretation
      of the derived chemometric models may be complicated because several sample
      properties often contribute to each principal component and because the influence
      of individual metabolites may be shared by several principal components.
      Furthermore, extensive signal overlap in (1)H-NMR spectra poses additional
      challenges to the interpretation of PCA models derived from such data. Orthogonal
      rotation of PCA models derived from (1)H-NMR spectra and HPLC-PDA profiles of the
      extracts of St. John's wort preparations facilitate interpretation of the model.
      Using the varimax criterion, rotation of loadings provides simpler conditions for
      understanding the influence of individual metabolites on the observed clustering.
      Alternatively, rotation of scores simplifies the understanding of the influence
      of whole metabolite profiles on the clustering of individual samples.

PMID- 19096995
TI  - In silico target fishing for rationalized ligand discovery exemplified on
      constituents of Ruta graveolens.
AB  - The identification of targets whose interaction is likely to result in the
      successful treatment of a disease is of growing interest for natural product
      scientists. In the current study we performed an exemplary application of a
      virtual parallel screening approach to identify potential targets for 16
      secondary metabolites isolated and identified from the aerial parts of the
      medicinal plant RUTA GRAVEOLENS L. Low energy conformers of the isolated
      constituents were simultaneously screened against a set of 2208 pharmacophore
      models generated in-house for the IN SILICO prediction of putative biological
      targets, i. e., target fishing. Based on the predicted ligand-target
      interactions, we focused on three biological targets, namely acetylcholinesterase
      (AChE), the human rhinovirus (HRV) coat protein and the cannabinoid receptor type
      2 (CB (2)). For a critical evaluation of the applied parallel screening approach,
      virtual hits and non-hits were assayed on the respective targets. For AChE the
      highest scoring virtual hit, arborinine, showed the best inhibitory IN VITRO
      activity on AChE (IC (50) 34.7 muM). Determination of the anti-HRV-2 effect
      revealed 6,7,8-trimethoxycoumarin and arborinine to be the most active antiviral
      constituents with IC (50) values of 11.98 muM and 3.19 muM, respectively. Of
      these, arborinine was predicted virtually. Of all the molecules subjected to
      parallel screening, one virtual CB (2) ligand was obtained, i. e., rutamarin.
      Interestingly, in experimental studies only this compound showed a selective
      activity to the CB (2) receptor ( Ki of 7.4 muM) by using a radioligand
      displacement assay. The applied parallel screening paradigm with constituents of
      R. GRAVEOLENS on three different proteins has shown promise as an IN SILICO tool
      for rational target fishing and pharmacological profiling of extracts and single
      chemical entities in natural product research.

PMID- 19096997
TI  - Development and validation of an RP-HPLC method for quantification of cinnamic
      acid derivatives and kaurane-type diterpenes in Mikania laevigata and Mikania
      glomerata.
AB  - MIKANIA GLOMERATA and MIKANIA LAEVIGATA (Asteraceae) are medicinal plants
      popularly named 'guaco' in Brazil. The leaves of both species are used to treat
      respiratory diseases, with coumarin (CO) and kaurane-type diterpenes being
      regarded as the bioactive constituents. A new and simple RP-HPLC method was
      developed and validated for the simultaneous quantification of CO, O-coumaric
      (OC), benzoylgrandifloric (BA), cinnamoylgrandifloric (CA) and kaurenoic (KA)
      acids in the species. Optimal separation was achieved with an alternating
      gradient elution of methanol and acetonitrile and detection was carried out by
      DAD at three different wavelengths: 210 nm for CO, OC, KA; 230 nm for BA; and 270
      nm for CA. The extracts showed good stability during 42 hours under normal
      laboratory conditions (temperature of 23 +/- 2 degrees C). The standard curves
      were linear over the range 0.5 - 5.0 microg (CO), 0.25 - 4.0 microg (OC), 1.0 -
      8.0 microg (BA), 0.5 - 3.0 microg (CA) and 0.8 - 12.0 microg (KA), with R(2) >
      0.999 for all compounds. The method showed good precision for intra-day (RSD <
      4.6 %) and inter-day assays (RSD < 4.4 %). The recovery was between 99.9 and
      105.3 %, except for CO and OC in M. glomerata (73.2 - 91.6 % and 86.3 - 117.4 %,
      respectively). The limits of quantification and detection were in the range of
      0.025 - 0.800 microg and 0.007 - 0.240 microg. The method was tested for new and
      old columns, temperature variation (26 and 28 degrees C) and by different
      operators in the same laboratory. The method was successfully applied to samples
      of both species.

PMID- 19096998
TI  - Low levels of gibberellic acid control the biosynthesis of ajmalicine in
      Catharanthus roseus cell suspension cultures.
AB  - In periwinkle cell suspensions, amounts of gibberellic acid ranging from 10 ( -
      10) M to 10 ( - 7) M significantly antagonized, in a dose-dependant manner, the
      stimulation of ajmalicine biosynthesis by cytokinins (CKs). This inhibitory
      effect was strictly correlated with the abolition of the expression of two genes
      encoding enzymes of the monoterpenoid indole alkaloid (MIA) biosynthetic pathway
      and was normally upregulated after CK treatments. Moreover, low concentrations of
      the gibberellin biosynthesis inhibitor paclobutrazol could reverse the inhibitory
      effects of low auxin levels on ajmalicine accumulation in the cells. On the other
      hand, gibberellic acid could not affect the expression of two type-A response
      regulators considered to be CK primary response genes in periwinkle cells. The
      antagonistic effects of gibberellins and cytokinins on MIA biosynthesis and their
      possible impact on elements of the signal transduction are discussed.

PMID- 19096999
TI  - Machilin A isolated from Myristica fragrans stimulates osteoblast
      differentiation.
AB  - This study evaluated the stimulatory effects of machilin A and structurally
      related lignans isolated from Myristica fragrans on osteoblast differentiation.
      In two IN VITRO osteoblast differentiation models, machilin A stimulated
      osteoblast differentiation via activation of p38 MAP kinase. Lignans isolated
      from Myristica fragrans also stimulated osteoblast differentiation in MC3T3-E1
      cells; the lignans included macelignan, machilin F, nectandrin B, safrole,
      licarin A, licarin B, myristargenol, and meso-dihydroguaiaretic acid. These data
      suggest that lignans isolated from Myristica fragrans have anabolic activity in
      bone metabolism.

PMID- 19097000
TI  - Prenylisoflavonoids from Erythrina senegalensis as novel HIV-1 protease
      inhibitors.
AB  - Eight compounds were isolated from the CH (2)Cl (2) extracts of ERYTHRINA
      SENEGALENSIS to assess HIV-1 protease (PR) activity inhibition. The prenylated
      isoflavone structures, identified by spectroscopic analysis, were 8-prenylluteone
      ( 1), auriculatin ( 2), erysenegalensein O ( 3), erysenegalensein D ( 4),
      erysenegalensein N ( 5), derrone ( 6), alpinumisoflavone ( 7), and 6,8
      diprenylgenistein ( 8). The constituents showed dose-dependent inhibitory
      activities on HIV-1 PR with IC (50) values from 0.5 to 30.0 muM. Compounds 1 - 5
      possessing two hydroxy groups in the 2' and 4' positions of the B ring, potently
      inhibited HIV-1 PR activity. In addition, 6,8-diprenylgenistein ( 8) with two
      prenyl groups in the 6 and 8 positions of the A ring and one hydroxy group in the
      4' position of B-ring was the most potent HIV-1 PR inhibitor.

PMID- 19097001
TI  - Cytotoxicity and phytotoxicity of trichothecene macrolides from Myrothecium
      gramminum.
AB  - (1)H-NMR guided fractionation of the EtOAc extract from the culture of
      Myrothecium gramminum (strain no. 3.1968) led to the isolation of eight cytotoxic
      trichothecene macrolides ( 1 - 8), all being substantially inhibitory against
      HepG2 (human hepatocellular carcinoma) and KB (human nasopharynyeal epidermoid
      tumor) cell lines with IC (50) values ranging from 2.2 to 12.2 mug/mL. Their
      inactivity to or weaker action on Vero cells (IC (50) values > 20 microg/mL,
      originated from the African green monkey kidney) highlighted preliminarily the
      nature of the selective cytotoxicity of the fungal metabolites against the test
      cancer cell lines. In addition, verrucarin A ( 1) and roridin A ( 5) were found
      to be potent inhibitors of the radial growth of Echinochloa crusgalli with
      corresponding IC (50) values of (7.96 +/- 0.31) x 10 ( - 6) and (9.18 +/- 0.44) x
      10 ( - 6) M, respectively, which were more potent than that of the positive
      control (2,4-dichlorophenoxyacetic acid) [(9.40 +/- 0.04) x 10 ( - 5) M].

PMID- 19097002
TI  - [Unwanted side effects of antibacterials--a diagnostic challenge].
AB  - We present three cases of rare side effects which appeared to be attributable to
      antibacterial drug treatment. A 57-year-old female patient was admitted to
      hospital due to increasing dyspnea. Computed tomography revealed interstitial
      lung fibrosis which was attributed to the toxic effects of nitrofurantoin (50
      mg/d) that the patient used for approximately one year for recurrent urinary
      tract infection. She died two weeks after hospital admission due to acute
      respiratory failure. A 20-year-old male patient presented with most intense
      headache and psychomotor deceleration. Pseudotumor cerebri, which was suspected
      to be the underlying cause, is described as a rare side effect of minocyclin
      which the patient has taken for acne pustulosa (100 mg single dose). After
      dechallenge of minocyclin, neurological symptoms quickly subsided. A 82-year-old
      female patient used moxifloxacin (400 mg/d) for febrile bronchopulmonary
      infection for one week. During this therapy, confusion and severe dementia
      presented and remained for more than two months after discontinuation. The
      demential syndrome appears to be possibly related to the fluoroquinolone use. In
      summary, adverse drug effects not pertaining to the primary physician's field are
      especially difficult to identify. Most importantly, rare side effects must be
      borne in mind by the prescribing physician.

PMID- 19097003
TI  - Role of hip arthrodesis in current practice: long term results following
      conversion to total hip arthroplasty.
AB  - BACKGROUND: Hip arthrodesis was once considered as a preferred treatment option
      in young people with hip arthritis. The purpose of this retrospective study was
      to evaluate the long term outcome following conversion of hip arthrodesis to
      arthroplasty. The main indications for conversion were back pain and ipsilateral
      muscular or knee pain. METHODS: Sixty-eight procedures in 67 patients performed
      between 1963 and 2000 at Wrightington Hospital were evaluated. RESULTS: The mean
      age at the time of hip arthrodesis was 16.7 years (3 to 39 years). The mean age
      at the time of conversion was 48.7 years (24 to 74 years). The Merle d'Aubigne
      score improved from a mean of 8.81 pre-operatively to 13.6 at the latest follow
      up. Complications included DVT (3 patients), transient foot drop (1 patient), and
      hepatitis following blood transfusion (1 patient). Seven patients required
      further revision surgery following conversion. CONCLUSIONS: Arthrodesis remains a
      sensible and safe treatment option maintaining independent mobility without
      multiple operations or significant bone loss for 20-30 years which subsequently
      can be successfully converted to an arthroplasty.

PMID- 19097004
TI  - The polished tri-tapered stem for cement-in-cement revision hip arthroplasty, a
      reliable and reproducible technique?
AB  - The object of this study was to determine the short to medium term outcome of
      cementing a highly polished tapered implant into the old cement mantle once
      damaged cement is removed at the time of revision hip surgery. A consecutive
      series of 36 patients underwent c-stem cement-in-cement revision hip arthroplasty
      between June 2000 and April 2006. The primary outcome measure was the validated
      shortened Western Ontario and McMaster Universities (WOMAC) score, secondary
      outcomes were the Orthowave company patient satisfaction survey, radiological
      analysis, and general complications. The follow-up period was between 12 and 84
      months (average 48.86 months). The mean post op WOMAC score at latest follow-up
      was 10.89 (0 to 29). Two patients died with their hip in situ. Two patients had
      radiological signs of prosthesis loosening on follow-up. Complications included:
      one sacral plexus palsy which had a partial recovery and one intra-operative
      periprosthetic fracture. One patient underwent cup revision for recurrent
      dislocation. Cement within cement revision hip arthroplasty using a highly
      polished tapered stem in the short to medium term provides satisfactory
      functional outcomes and is associated with a low complication rate and good
      survivorship.

PMID- 19097005
TI  - Femoral revision with impaction allografting and an uncemented femoral component.
AB  - A technique for uncemented revision of the femoral component which combines
      impaction allografting and the use of a long-stemmed proximally coated titanium
      prostheses (Bimetric, Biomet Inc.) is described. The results after a mean follow
      up of 112 months are reported. From 1991 to 1995 femoral component revision for
      aseptic loosening was performed on 100 hips. In 14 cases (14%) an intraoperative
      fracture occurred and 7 patients (7%) had other postoperative complications.
      Seventeen patients (17%) required further revision, 10 because of aseptic
      loosening. Of 50 surviving patients with retained implants 88% had no pain, 10%
      had slight pain and only 2% had severe pain. Thirty-eight patients had
      radiographic signs of remodelling of the graft and/or cortical repair. In cases
      with a successful outcome, the results have been encouraging in relation to
      clinical performance, regeneration of bone and implant survival.

PMID- 19097006
TI  - Optimizing for head height, head offset, and canal fit in a set of uncemented
      stemmed femoral components.
AB  - When inserting an uncemented hip stem, the objectives are to obtain a close fit
      of the stem in the canal and anatomic head placement. Our goals were to formulate
      a set of stems which would satisfy these two objectives, and to test the
      resulting templates on sequential radiographs of hip replacement patients. Using
      98 cases for which a custom primary hip had been designed, thirteen dimensional
      parameters for a hip stem were defined, most importantly proximal medial width
      (PMW), proximal lateral width (PLW), head offset (HOF), head height (HHT), mid
      stem diameter (BD), and distal diameter (DD). These parameters were analyzed in
      155 patients' radiographs, and the resulting data were evaluated to obtain the
      optimal combinations of parameters. A 14-size stem system was defined and
      evaluated on the AP radiographs of 103 successive hip replacement patients. For
      each stem diameter between 11 and 17 mm, two pairs of PMW and PLW values,
      equivalent to 'varus' and 'valgus' shapes, provided the best fit for the
      population of radiographs. The template analysis showed that out of 103 cases,
      93% of offsets were within 4mm of ideal, while 81% of heights were within 1mm of
      ideal, and 99% were within 4mm of the ideal. Canal fit was within 1.5mm in the
      proximal-medial Gruen Zone 7 in 58% of the cases. The dimensional parameters of
      the 14 size system enabled the close matching of the important dimensional
      parameters simultaneously. The error that did occur could largely be corrected by
      modular heads and by minor canal broaching. By providing two stem shape
      variations for each stem diameter, our system achieved an accurate head center
      position while simultaneously obtaining a sufficiently close fit in the canal.

PMID- 19097007
TI  - Early discharge after hip arthroplasty with home support: experience at a UK
      District General Hospital.
AB  - One hundred and thirty-eight consecutive patients undergoing hip arthroplasty and
      accelerated discharge at our institution over 6 months were reviewed. Our
      protocol included transfer to a dedicated home support team. No minimal incision
      techniques or special anaesthetic/analgesic techniques were used. 66% of patients
      having primary joint replacements went home by the third post operative day and
      91% by the fourth day. Re-admission rates were under 1% whilst under the care of
      the home support team. Patient satisfaction was high. 94% said they would use the
      service again. This protocol has saved over 1500 bed days per year whilst
      maintaining standards of care.

PMID- 19097008
TI  - Medium to long term results of the Exeter bipolar hemiarthroplasty for femoral
      neck fractures in active, independent patients. 5-13 year follow-up.
AB  - We present the clinical and radiographic outcome of 49 Exeter bipolar
      hemiarthroplasties for femoral neck fractures in 49 patients with a median age of
      71 years at the time of operation. Median length of follow-up was 7.1 years (5 to
      13). There was one dislocation, and one peri-prosthetic fracture. There were no
      revisions for infection, acetabular erosion or stem loosening. Twenty-six
      patients had died by the time of final follow-up with an overall 5 year
      cumulative survival of 60.2%. Thirty day mortality was 36% in patients with an
      ASA score of 3. We present excellent clinical and radiological medium to long
      term results with no evidence of acetabular erosion. However, careful patient
      selection is necessary to avoid high early mortality rates.

PMID- 19097009
TI  - Quality of life in different age groups after metal-on-metal hip resurfacing
      arthroplasty.
AB  - Hip resurfacing arthroplasty is known to improve quality of life (QoL) and allow
      increased activity levels in young patients. It is, however, traditionally
      offered to the younger age group of patients, largely those aged under 60 years.
      We studied 42 consecutive patients (42 hips) aged 60 years or over (mean age 64)
      and 41 consecutive patients (42 hips) under this age (mean age 49), all of whom
      had undergone a metal-on-metal hip resurfacing arthroplasty. A modified Harris
      hip score was translated to QoL scores using the Rosser Index Matrix immediately
      pre-operatively, and at six weeks, six months, one year and four years after
      surgery. We found a significant improvement in QoL for both groups (p <0.0001)
      but no difference between the two groups. The maximum improvement was reached one
      year after surgery. Implant survival at four years was also similar (97.6% for
      group I and 100% for group II). We thus conclude that in carefully selected
      active patients aged 60 years and over, hip resurfacing arthroplasty provides
      significant and equal QoL improvement as it does for those under this age with
      similar implant survival. For this reason, age alone should not influence a
      surgeon's decision to proceed with a hip resurfacing arthroplasty.

PMID- 19097010
TI  - The treatment of femoral neuropathy due to pseudotumour caused by metal-on-metal
      resurfacing arthroplasty.
AB  - Concerns now exist about the long-term biological effects of exposure to
      orthopaedic metal alloys, particularly serum cobalt and chromium ions derived
      from metal-on-metal wear debris in these patients. A pseudotumour mass
      complicating metal-on-metal resurfacing arthroplasty has been recognized by
      orthopaedic oncologists and specialist hip units. Pseudotumours may also present
      with a major nerve palsy. Two cases of femoral neuropathy due to pseudotumour
      masses caused by metal-on-metal resurfacing arthroplasty are presented.
      Preoperative neurophysiological studies showed severe and irreversible
      pathological changes to nerve function with neurohistopathological evidence of
      complete nerve destruction with a previously unreported pathological appearance.
      This may represent a previously unrecognized pathological process, possibly
      'toxic' in nature, resulting from metal-on-metal wear debris. Prolonged follow-up
      and detailed clinical assessment of patients after hip resurfacing arthroplasty
      is advocated with planned and expeditious revision of any patient in whom
      evidence of femoral neuropathy develops.

PMID- 19097011
TI  - A displaced acetabular component causing femoral neck notching following hip
      resurfacing.
AB  - We describe the case of a patient who developed a notch on the femoral neck
      following a hip resurfacing operation as a result of a displaced acetabular
      component. The acetabular cup displaced in the coronal plane and impinged on the
      femoral neck leading to a large notch in the inferior femoral neck.

PMID- 19097012
TI  - Total hip arthroplasty in a patient affected by post-traumatic acetabular non
      union: case report and review of the literature.
AB  - Total hip arthroplasty in the presence of acetabular non-union can be demanding.
      The irregular anatomy, the defect, and the presence of fibrous and necrotic
      tissue can hamper insertion of the acetabular component. We present a case of
      total hip arthroplasty in a patient with post-traumatic necrosis of the femoral
      head and non-union of the acetabulum and follow-up one year after the operation.
      Following accurate preoperative planning, removal of the pseudarthrosis material,
      and the use of the femoral head as an autograft, it was possible to insert the
      acetabular cup satisfactorily in a single-stage procedure.

PMID- 19097013
TI  - Acute Q-fever and history taking--a lesson learned.
AB  - A 50-year-old patient underwent a routine primary total hip replacement. Soon
      after surgery, he developed acute respiratory failure from post-operative sepsis.
      His condition deteriorated rapidly despite supportive management and he required
      admission into intensive care unit for assisted ventilation. It took almost one
      week before the underlying cause of the deterioration was determined to be
      unrelated to complications of surgery. A diagnosis of Q-fever was made following
      detailed attention to the clinical history. Appropriate treatment was started and
      the patient made a full recovery. The diagnosis was confirmed later following
      discharge from hospital.

PMID- 19097017
TI  - More choice, more issues, more "chemistry".

PMID- 19097014
TI  - Fatal fat embolism following femoral head resection in total hip arthroplasty.
AB  - We report a rare complication during primary total hip arthroplasty. A fatal fat
      pulmonary embolism immediately followed removal of the femoral head, prior to
      further preparation of the acetabulum or femoral shaft. Fat embolism syndrome is
      a well-known complication during total joint arthroplasty, usually attributed to
      preparation of the femoral shaft, particularly intramedullary reaming and
      insertion of the prosthesis. These risk factors have previously been identified
      in the literature. We believe that this case highlights the need for further
      research to establish the intramedullary pressures during the processes of
      dislocation and resection of the femoral neck and the attendant risk.

PMID- 19097021
TI  - Toxicity of delta-phenothrin and resmethrin to non-target insects.
AB  - BACKGROUND: The susceptibility of adult house cricket, Acheta domesticus (L.),
      adult convergent lady beetle, Hippodamia convergens (Guerin-Meneville), and
      larval fall armyworm, Spodoptera frugiperda (JE Smith), to resmethrin and delta
      phenothrin synergized with piperonyl butoxide (PBO) was evaluated in a laboratory
      bioassay procedure. RESULTS: The 1 day LC(50) values for resmethrin + PBO were
      23.2, 32.08 and 307.18 ng cm(-2) for A. domesticus, H. convergens and S.
      frugiperda respectively. The 1 day LC(50) values for delta-phenothrin + PBO were
      26.9, 74.91 and 228.57 ng cm(-2) for A. domesticus, H. convergens and S.
      frugiperda respectively. The regression relationship between species mortality
      and concentration explained 51-81% of the variation for resmethrin + PBO and 72
      97% of the variation for delta-phenothrin + PBO. The LC(50) values decreased with
      time for these insecticides for all surrogate species. In terms of sensitivities
      among the insects to resmethrin + PBO and delta-phenothrin + PBO, A. domesticus
      was most sensitive, followed by H. convergens and then S. frugiperda. CONCLUSION:
      The results indicate that resmethrin + PBO was generally more toxic than delta
      phenothrin + PBO. Based on the results, A. domesticus seems to be a good
      surrogate species for estimating potential non-target terrestrial insect impacts
      from exposure to pyrethroids used in public health applications.

PMID- 19097022
TI  - Toxicity of emamectin benzoate to Cydia pomonella (L.) and Cydia molesta (Busck)
      (Lepidoptera: Tortricidae): laboratory and field tests.
AB  - BACKGROUND: Emamectin benzoate is a novel macrocyclic lactone insecticide derived
      from naturally occurring avermectin molecules isolated by fermentation from the
      soil microorganism Streptomyces avermitilis Kim & Goodfellow. The present study
      aims to evaluate the toxicity of emamectin benzoate to codling moth, Cydia
      pomonella (L.), and oriental fruit moth, C. molesta (Busck), under laboratory and
      semi-field conditions. RESULTS: Dose response bioassays showed that emamectin
      benzoate had a high level of intrinsic toxicity to early-stage larvae of both
      species, and that contact activity might contribute significantly to mortality.
      In the semi-field trials, residual toxicity lasted for more than 1 week. Ovicidal
      activity was recorded only for C. pomonella (approximately 30%), irrespective of
      the concentrations tested. Field trials confirmed the efficacy of emamectin
      benzoate on codling moth when applied at 7 day intervals. Fruit damage, both from
      the first and second generations, was comparable with that on treatment with
      chlorpyrifos-ethyl, used as a chemical reference. CONCLUSION: Emamectin benzoate
      may be considered a valuable tool for the control of codling moth as a component
      of an IPM programme. Its collective advantages are: high efficacy, lack of cross
      resistance with currently used products, control of secondary pests such as
      oriental fruit moth and selective toxicity that spares beneficials.

PMID- 19097023
TI  - Sublethal effects of spinosad on survival, growth and reproduction of Helicoverpa
      armigera (Lepidoptera: Noctuidae).
AB  - BACKGROUND: Helicoverpa armigera (Hubner) is one of the most important pests in
      many countries. Spinosad is used widely for the control of pests, but there is
      sparse information available regarding its sublethal effects on H. armigera.
      Here, the authors attempt to investigate the sublethal effects of spinosad on H.
      armigera in order to reveal the negative, non-lethal impact of insecticides on
      this pest. RESULTS: The toxicity of spinosad against H. armigera was determined
      under laboratory conditions by oral exposure of late second-instar larvae to the
      compound. The 48 h LC(50) and 72 h LC(50) values of spinosad to this pest were
      found to be 0.41 mg kg(-1) and 0.35 mg kg(-1) respectively. Spinosad at sublethal
      concentrations significantly extended the developmental time of survivor larvae,
      and reduced larval wet weight. Post-exposure effects were indicated by decreased
      pupation ratio and pupal weight, by prolonged prepupal and pupal periods and by
      decreased emergence ratio, fecundity and longevity of adults. CONCLUSION: These
      results suggest that the combination of lethal and sublethal effects of spinosad
      might affect pest population dynamics significantly by decreasing its survival
      and reproduction, and by delaying its development.

PMID- 19097024
TI  - Lack of fitness costs associated with pyriproxyfen resistance in the B biotype of
      Bemisia tabaci.
AB  - BACKGROUND: The insect growth regulator pyriproxyfen has provided effective
      control of the whitefly Bemisia tabaci Gennadius in many countries. Here, whether
      or not fitness costs were associated with pyriproxyfen resistance in a laboratory
      selected resistant strain (QC02-R) of the B biotype was determined. RESULTS:
      Mortality caused by pyriproxyfen and fitness traits over time were measured in
      unselected and selected hybrid strains, which were created by crossing
      individuals of the resistant strain with individuals of a susceptible strain.
      Fitness costs were not associated with resistance in QC02-R, as mortality caused
      by pyriproxyfen did not increase over time in unselected hybrid strains and
      fitness traits were similar in unselected and selected hybrid strains. Using a
      new method to examine the inheritance of resistance, based on data from fitness
      cost experiments, it was estimated that pyriproxyfen resistance is controlled by
      two loci in the QC02-R strain. CONCLUSION: The lack of fitness costs associated
      with pyriproxyfen resistance could promote the evolution of resistance in field
      populations with similar traits to QC02-R.

PMID- 19097025
TI  - Glutamine synthetase mutation conferring target-site-based resistance to
      glufosinate in soybean cell selections.
AB  - BACKGROUND: Glufosinate-resistant soybean cells were achieved through direct
      selection of diploid cells in the suspension culture. Here, the mutations in the
      glutamine synthetase (GS) gene are described to understand the evidence pointing
      to the functional role of the GS gene in the herbicide sensitivity of the mutant
      cells. RESULTS: Based on the I(50) values, dose-response experiments at the cell
      level showed that the resistance ratio of the resistant cell was 50-fold, whereas
      the in vitro inhibition of GS activity required a 4.56-fold greater concentration
      of glufosinate in the resistant cell than in the untreated control. Comparison of
      the nucleotide sequences identified nine point differences in the GS gene between
      the resistant and untreated cells, leading to eight amino acid substitutions in
      the deduced polypeptide sequence. Northern hybridization of the GS mRNA showed
      that the accumulation of GS gene mRNA transcript in resistant cells was higher
      than that in the untreated cells. CONCLUSION: Changes in sensitivity to
      glufosinate have been related to mutations at the binding site of the herbicide
      on the glutamine synthetase. His(249) is one of the residues implicated in the
      binding domain for the substrate and inhibitor, and hence the exchange of this
      residue with tyrosine plays a role in lowering the sensitivity of the mutated
      enzyme.

PMID- 19097026
TI  - Coactivity of sulfide ingredients: a new perspective of the larvicidal activity
      of garlic essential oil against mosquitoes.
AB  - BACKGROUND: The activity of several garlic oil ingredients against Culex pipiens
      L. larvae was studied. In addition to diallyl sulfide (DS) and diallyl disulfide
      (DDS), the garlic oils used included one essential oil (EO) and two semi
      synthetic garlic essential oils (SSGEO1 and SSGEO2), which resulted from the
      enrichment of EO with DS and DDS standards respectively. The oils were compared
      with respect to their toxicity. RESULTS: The chemical composition of the tested
      oils was evaluated by means of gas chromatography-mass spectrometry. Experimental
      data from the tested samples revealed high toxicity. In detail, DDS (6.09 mg L(
      1)) was the most active, followed by SSGEO2 (7.05 mg L(-1)) and EO (8.01 mg L(
      1)), while SSGEO1 and DS were relatively inactive. CONCLUSION: The addition of
      DDS to EO did not change the toxic effect of the essential oil, whereas the
      presence of DS in excess produced an enriched essential oil with low toxicity.
      Furthermore, the antagonistic effect of DS and DDS against the other components
      of EO was shown by the application of two equations obtained from the literature.
      Their larvicidal performances were correlated, for the first time, with their
      detailed chemical composition. Data analysis strongly indicated the toxicity of
      the other EO sulfur ingredients.

PMID- 19097027
TI  - Field evaluations of insecticide treatment regimens for control of the common bed
      bug, Cimex lectularius (L.).
AB  - BACKGROUND: Because bedbugs, Cimex lectularius L., have not been a problem in the
      USA for over 40 years, few insecticide products are labeled for their control.
      Most products that are labeled for bedbugs are pyrethroids. However, recent
      studies indicate that field-collected bedbugs may be resistant to pyrethroids.
      There are also non-pyrethroid products labeled for bedbugs, but, like the
      pyrethroids, none of these products has been evaluated for field efficacy. This
      study evaluated the efficacy of two insecticide treatment regimens for bedbugs in
      multi-unit housing. Both of the treatments included multiple products currently
      being used by the pest management industry. RESULTS: The 'traditional' treatment
      consisted of applications of pyrethroid products and an insect growth regulator.
      The 'novel' treatment consisted of applications of non-pyrethroid products. The
      traditional treatment significantly reduced the number of bedbugs from 39.8 +/-
      10.1 per unit prior to treatment to 2.2 +/- 1.0 at the end of the test period (P
      = 0.02; 95% reduction). The number of live bedbugs in the 'novel' treatment was
      also significantly reduced from 71.4 +/- 25.3 bedbugs per unit to 10.2 +/- 4.4
      after 8 weeks (86% population reduction). CONCLUSIONS: Although both treatment
      regimens reduced bedbug numbers, the fact that bedbugs were not eliminated after
      multiple applications suggests that the insecticides, applied at the current
      label rates, were inadequate. These results suggest that a more integrated
      approach to bedbug control is necessary in multi-unit housing situations.

PMID- 19097028
TI  - Novel recombinant adenovirus type 41 vector and its biological properties.
AB  - BACKGROUND: Human adenovirus serotype 41 (Ad41) is a natural pathogen of the
      digestive tract and can cause gastroenteritis. There has been interest in
      reconstructing Ad41 as a gene delivery vector targeting the gastrointestinal
      tract, which is hampered by its fastidiousness. METHODS: An Ad41 E1B55K
      transduced 293 cell line (293E12) was established as the packaging cell line. A
      backbone plasmid (pAdbone41) and a shuttle plasmid (pSh41-CMV) were constructed
      based on the Ad41 genome. Replication-defective adenovirus (Ad41-GFP) was rescued
      in 293E12 after being transfected with the linearized adenoviral plasmid, which
      was generated by homologous recombination of pAdbone41 and the shuttle plasmid
      carrying the GFP gene in Escherichia coli strain BJ5183. The packaging ability of
      293E12, the stability of the Ad41-GFP genome and the acid-resistant property of
      Ad41-GFP were all investigated. RESULTS: A 293E12 cell could produce
      approximately 9000 viral particles of Ad41-GFP, which is close to the amount in
      the control virus (Ad5-GFP) amplified in one 293 cell. Ad41-GFP contained a
      genetically stable genome after being passaged eight times in 293E12 cells. More
      significantly, Ad41-GFP was more resistant to acid exposure than Ad5-GFP. It
      retained almost complete viability when exposed to hydrochloric acid with a pH
      value of 2 for 30 min, whereas Ad5-GFP lost 99% of its viability under the same
      conditions. Ad41-GFP was also more tolerant to treatment with artificial
      digestive fluid. CONCLUSIONS: An Ad41 vector system was successfully constructed,
      which consisted of the backbone plasmid, shuttle plasmid and packaging cell line
      293E12. This system can be utilized to generate genetically stable and acid
      resistant recombinant Ad41 carrying any gene of interest.

PMID- 19097029
TI  - Short hairpin RNAs against eotaxin or interleukin-5 decrease airway eosinophilia
      and hyper-responsiveness in a murine model of asthma.
AB  - BACKGROUND: Eosinophilia plays the major role in the pathogenesis of asthma and
      correlates with the up-regulation of eotaxin, which, together with interleukin
      (IL)-5, is important for differentiation, chemo-attraction, degranulation, and
      survival of eosinophils in local tissue. In a previous study, we found that
      administration of lentivirus-delivered short hairpin RNA (shRNA) to suppress the
      expression of IL-5 inhibited airway inflammation. The present study aimed to
      investigate the role of eotaxin shRNA and the synergistic effect of eotaxin and
      IL-5 shRNAs on airway inflammation in an ovalbumin (OVA)-induced murine model of
      asthma. METHODS: Lentivirus-delivered shRNAs were used to suppress the expression
      of eotaxin and/or IL-5 in local tissue in an OVA-induced murine asthma model.
      RESULTS: Intra-tracheal administration of lentivirus containing eotaxin shRNA
      expressing cassette (eoSEC3.3) efficiently moderated the characteristics of
      asthma, including airway hyper-responsiveness, cellular infiltration of lung
      tissues, and eotaxin and IL-5 levels in bronchio-alveolar lavage fluid.
      Administration of lentiviruses expressing IL-5 or eotaxin shRNAs (IL5SEC4 +
      eoSEC3.3) also moderated the symptoms of asthma in a mouse model. CONCLUSIONS:
      Local delivery of lentiviruses expressing IL-5 and eotaxin shRNAs provides a
      potential tool in moderating airway inflammation and also has the potential for
      developing clinical therapy based on the application of shRNAs of chemokines and
      cytokines involved in T helper 2 cell inflammation and eosinophilia.

PMID- 19097030
TI  - Patient preferences for screening in the first trimester.
AB  - OBJECTIVE: We theorized that a significant number of women would choose
      integrated screening (IS) over first trimester screening (FTS) and that
      demographic characteristics and baseline anxiety levels might predict which
      patients would choose each test. We also hypothesized that screening results
      might alter patients' future preferences. METHOD: Patients underwent non
      directive genetic counselling and were offered FTS or IS. Prior to undergoing
      nuchal translucency (NT) ultrasound, patients were given surveys. These
      questionnaires were repeated in the second trimester and postpartum. They
      focussed on the patients' background, motivations for screening and anxiety
      level. RESULTS: Out of 110 patients surveyed, 81 returned their initial
      questionnaire. 60% of these patients chose FTS and 40% chose IS. There were no
      demographic differences between the groups. FTS patients desired early
      reassurance while IS patients wanted the 'most information' and the lowest chance
      of needing diagnostic testing. In all, 47 women returned second trimester
      questionnaires and 35 women returned postpartum surveys. These surveys
      demonstrated that women's motivations remained constant over time. Of the five
      screen positive results, only one woman regretted her screening choice.
      CONCLUSION: One cannot predict patients' screening preferences, thus both FTS and
      IS should be offered. Given non-directive counselling, patients are generally
      satisfied with their screening choices.

PMID- 19097031
TI  - Decisional needs assessment regarding Down syndrome prenatal testing: a
      systematic review of the perceptions of women, their partners and health
      professionals.
AB  - OBJECTIVE: To identify decisional needs of women, their partners and health
      professionals regarding prenatal testing for Down syndrome through a systematic
      review. METHODS: Articles reporting original data from real clinical situations
      on sources of difficulty and/or ease in making decisions regarding prenatal
      testing for Down syndrome were selected. Data were extracted using a taxonomy
      adapted from the Ottawa Decision-Support Framework and the quality of the studies
      was assessed using Qualsyst validated tools. RESULTS: In all 40 publications
      covering 32 unique studies were included. The majority concerned women. The most
      often reported sources of difficulty for decision-making in women were pressure
      from others, emotions and lack of information; in partners, emotion; in health
      professionals, lack of information, length of consultation, and personal values.
      The most important sources of ease were, in women, personal values, understanding
      and confidence in the medical system; in partners, personal values, information
      from external sources, and income; in health professionals, peer support and
      scientific meetings. CONCLUSION: Interventions regarding a decision about
      prenatal testing for Down syndrome should address many decisional needs, which
      may indeed vary among the parties involved, whether women, their partners or
      health professionals. Very little is known about the decisional needs of partners
      and health professionals.

PMID- 19097032
TI  - PLAC4 and beta-HCG mRNA levels are not altered in the maternal circulation of
      pregnancies with trisomy 21.
AB  - OBJECTIVE: Beta-human chorionic gonadotropin (HCG) and pregnancy-associated
      plasma protein (PAPP-A) are placentally produced proteins whose levels are
      altered in pregnancies with trisomy 21. PLAC4 is located on chromosome 21 and its
      expression is restricted to the placenta. Here we investigated whether the levels
      of beta-HCG-, PAPP-A- and PLAC4 mRNA could be able to discriminate pregnancies
      whose fetus is affected by trisomy 21. METHOD: Hundred and forty-three blood
      samples from normal pregnancies and eight samples from trisomic pregnancies were
      collected. Total RNA was extracted from whole maternal blood, reverse-transcribed
      and the three mRNAs were quantified by real-time quantitative PCR. Hundred and
      nine controls were also tested for the serum levels of PAPP-A and HCG proteins.
      RESULTS: Beta-HCG and PLAC4 mRNAs were detected in all samples, in higher amounts
      than in plasma, whereas the detection rate for PAPP-A mRNA was below 10%. The
      levels of beta-HCG mRNA significantly correlated with the circulatory
      concentrations of the HCG protein. However, neither beta-HCG- nor PLAC4 mRNAs
      show a significant difference between cases and controls. CONCLUSION: Maternal
      blood levels of beta-HCG-, PLAC4- and PAPP-A mRNAs are not useful markers for the
      screening of pregnancies with trisomy 21 as their concentrations are either not
      significantly altered (beta-HCG and PLAC4) or too low to be detected (PAPP-A).

PMID- 19097034
TI  - Chromatin remodeling in embryonic stem cells: regulating the balance between
      pluripotency and differentiation.
AB  - Embryonic stem cells have an unlimited potential for self-renewal yet are
      pluripotent, capable of differentiating into three different germ layers and
      ultimately into multiple cell lineages. Key pluripotency specific factors
      maintain an undifferentiated ES cell phenotype while lineage specific factors
      work in opposition to promote cell specialization. In addition to these important
      transcriptional regulators, epigenetic modifiers play a defining role in
      regulating the balance between pluripotency and differentiation by promoting
      changes in chromatin structure.

PMID- 19097033
TI  - Effects of MAPK signaling on 1,25-dihydroxyvitamin D-mediated CYP24 gene
      expression in the enterocyte-like cell line, Caco-2.
AB  - We examined the role of the extracellular signal regulated kinases (ERK) in 1,25
      dihydroxyvitamin D (1,25(OH)(2)D(3))-induced gene expression in the
      differentiated Caco-2 cells. 1,25(OH)(2)D(3)-regulated expression of the 25
      hydroxyvitamin D, 24-hydroxylase (CYP24) gene (both natural gene and promoter
      construct) was strongly modulated by altering ERK activity (i.e., reduced by MEK
      inhibitors and dominant negative (dn) ERK1 and ERK2, activated by epidermal
      growth factor) but ERK inhibition had no effect on 1,25(OH)(2)D(3)-regulated
      expression of the transient receptor potential cation channel, subfamily V,
      member 6 (TRPV6). ERK5-mediated phosphorylation of the transcription factor Ets-1
      enhanced 1,25(OH)(2)D(3)-mediated CYP24 gene transcription in proliferating but
      not differentiated Caco-2 cells due to reduced levels of ERK5 and Ets-1 (total
      and phosphoprotein levels) in differentiated cells. MEK inhibition reduced
      1,25(OH)(2)D(3)-induced 3X-VDRE promoter activity but had no impact on the
      association of vitamin D receptor (VDR) with chromatin suggesting a role for co
      activator recruitment in ERK-modulation of vitamin D-regulated CYP24 gene
      activation. Chromatin immunoprecipitation assays revealed that the ERK1/2 target,
      mediator 1 (MED1), is recruited to the CYP24, but not the TRPV6, promoter
      following 1,25(OH)(2)D(3) treatment. MED1 phosphorylation was sensitive to
      activators and inhibitors of the ERK1/2 signaling and MED1 siRNA reduced
      1,25(OH)(2)D(3)-regulated human CYP24 promoter activity. This suggests ERK1/2
      signaling enhances 1,25(OH)(2)D(3) effects on the CYP24 promoter by MED1-mediated
      events. Our data show that there are both promoter-specific and cell stage
      specific roles for the ERK signaling pathway on 1,25(OH)(2)D(3)-mediated gene
      induction in enterocyte-like Caco-2 cells.

PMID- 19097035
TI  - The Ape-1/Ref-1 redox antagonist E3330 inhibits the growth of tumor endothelium
      and endothelial progenitor cells: therapeutic implications in tumor angiogenesis.
AB  - The apurinic/apyrimidinic endonuclease 1/redox factor-1 (Ape-1/Ref-1) is a multi
      functional protein, involved in DNA repair and the activation of redox-sensitive
      transcription factors. The Ape-1/Ref-1 redox domain acts as a cytoprotective
      element in normal endothelial cells, mitigating the deleterious effects of
      apoptotic stimuli through induction of survival signals. We explored the role of
      the Ape-1/Ref-1 redox domain in the maintenance of tumor-associated endothelium,
      and of endothelial progenitor cells (EPCs), which contribute to tumor
      angiogenesis. We demonstrate that E3330, a small molecule inhibitor of the Ape
      1/Ref-1 redox domain, blocks the in vitro growth of pancreatic cancer-associated
      endothelial cells (PCECs) and EPCs, which is recapitulated by stable expression
      of a dominant-negative redox domain mutant. Further, E3330 blocks the
      differentiation of bone marrow-derived mesenchymal stem cells (BMSCs) into
      CD31(+) endothelial progeny. Exposure of PCECs to E3330 results in a reduction of
      H-ras expression and intracellular nitric oxide (NO) levels, as well as decreased
      DNA-binding activity of the hypoxia-inducible transcription factor, HIF-1alpha.
      E3330 also reduces secreted and intracellular vascular endothelial growth factor
      expression by pancreatic cancer cells, while concomitantly downregulating the
      cognate receptor Flk-1/KDR on PCECs. Inhibition of the Ape-1/Ref-1 redox domain
      with E3330 or comparable angiogenesis inhibitors might be a potent therapeutic
      strategy in solid tumors.

PMID- 19097036
TI  - First-trimester contingent screening for Down syndrome can reduce the number of
      nuchal translucency measurements required.
AB  - BACKGROUND: To assess the performance of a two-stage screening protocol for Down
      syndrome based on initial serum marker analysis for all women and nuchal
      translucency (NT) measurement only in women with intermediate risks. METHODS:
      Biochemical marker and NT data in 10 189 women who had had combined ultrasound
      and biochemical (CUB) screening, were re-analysed using the contingent model. A
      risk was calculated from the results of the pregnancy-associated plasma protein A
      (PAPP-A) and free beta human chorionic gonadotrophin (FbetahCG) measurements and
      maternal age. For risks between 1 in 42 and 1 in 1000, the likelihood ratio from
      the NT measurement was incorporated and assessed against a final cut-off risk of
      1 in 250. RESULTS: A total of 3.1% unaffected and 61.4% Down syndrome pregnancies
      had risks>or=1:42. In women with risks<1 in 42 and >1 in 1000 (29%), a further
      2.7% unaffected pregnancies and 27.3% Down syndrome pregnancies had risks above 1
      in 250 when NT was incorporated. Overall detection rate was 88.6%, and false
      positive rate 5.8% (compared with 90.9% and 6.4% for CUB screening). NT
      measurements were required in 29% of women. CONCLUSIONS: Within first-trimester,
      contingent screening provides good sensitivity and specificity with the potential
      for considerable saving in ultrasound resources.

PMID- 19097037
TI  - Promises and pitfalls of first trimester sonographic markers in the detection of
      fetal aneuploidy.
AB  - First trimester sonographic markers are the only markers achieving detection
      rates above 50% in the prenatal detection of fetal aneuploidy. Although
      potentially they are the best markers, some concerns have arisen about its
      clinical application. Pitfalls may be due to inability to examine the markers,
      incorrect assessment, or incorrect interpretation of the findings. Markers may be
      unable to be examined due to maternal (maternal body habitus, previous surgery)
      or fetal reasons (incompatible fetal position or fetal movements). Causes of
      incorrect interpretation may be insufficient image magnification, incorrect
      caliper placement (nuchal translucency), incorrect insonation angle (nasal bone),
      venous contamination (ductus venosus), or arterial contamination (tricuspid
      regurgitation), among others. Venous contamination in ductus venosus waveforms
      may mimic an abnormal blood flow when it is normal, and the opposite can also
      occur. Finally, incorrect interpretation of a substantially increased nuchal
      translucency may lead to a false impression of an ominous fetal prognosis or may
      be confounded with a cystic hygroma.

PMID- 19097038
TI  - Preimplantation genetic diagnosis for fragile X syndrome: is there increased
      transmission of abnormal FMR1 alleles among female heterozygotes?
AB  - BACKGROUND: Fragile X syndrome is caused by a CGG triplet-repeat expansion
      mutation in the FMR1 gene. Previous studies have shown increased transmission of
      abnormal alleles in the 51-60 repeat range. This study was undertaken to evaluate
      the performance of preimplantation genetic diagnosis (PGD) for fragile X, and to
      assess the transmission rate of the abnormal FMR1 alleles in this setting.
      METHOD: The study included 18 fragile X carriers who applied for PGD. FMR1 CGG
      repeats ranged from 70 to 300. PGD was performed using multiplex-nested PCR, with
      simultaneous amplification of the CGG repeat region and several polymorphic
      markers, and sex chromosome markers. RESULTS: Four patients had a poor ovarian
      response, and could not undergo PGD. The remaining 14 patients underwent 47 PGD
      cycles. A total of 565 oocytes were aspirated. Of the 386 embryos that were
      successfully biopsied, 18 (6.4%) could not be analyzed due to amplification
      failure, and 12 (4.3%) had sex chromosomal abnormalities. Of the remaining 250
      embryos, the abnormal allele was transmitted to 124 embryos (49.6%) compared to
      126 (50.4%) for the normal allele. This difference was not statistically
      significant. Only embryos carrying the normal allele were transferred, resulting
      in 7 clinical pregnancies (18% per embryo transfer). CONCLUSIONS: Our results
      demonstrate that PGD for fragile X is feasible, and that carriers transmit the
      abnormal allele at the same frequency as the normal allele.

PMID- 19097039
TI  - Classroom implications of recent research into literacy development: from
      predictors to assessment.
AB  - We outline how research into predictors of literacy underpins the development of
      increasingly accurate and informative assessments. We report three studies that
      emphasize the crucial role of speech and auditory skills on literacy development
      throughout primary and secondary school. Our first study addresses the effects of
      early childhood middle ear infections, the potential consequences for speech
      processing difficulties and the impact on early literacy development. Our second
      study outlines how speech and auditory skills are crucially related to early
      literacy in normally developing readers, whereas other skills such as motor,
      memory and IQ are only indirectly related. Our third study outlines the on-going
      impact of phonological awareness on reading and wider academic achievement in
      secondary-school pupils. Finally, we outline how teachers can use the current
      research to inform them about which assessments to conduct, and how to interpret
      the results.

PMID- 19097040
TI  - Adjusting life for quality or disability: stylistic difference or substantial
      dispute?
AB  - This paper focuses on the contrast between describing the benefit of a healthcare
      intervention as gain in health (QALY-type ideas) or a disability reduction (DALY
      type ideas). The background is an apparent convergence in practice of the work
      conducted under both traditions. In the light of these methodological
      developments, we contrast a health planner who wants to maximise health and one
      who wants to minimise disability. To isolate the effect of framing the problem
      from a health or a disability perspective, we do not use age-weighting in
      calculating DALY and employ a common discounting methodology and the same set of
      quality of life weights. We find that interventions will be ranked in a
      systematically different way. The difference, however, is not determined by the
      use of a health or a disability perspective but by the use of life expectancy
      tables to determine the years of life lost. We show that this feature of the DALY
      method is problematic and we suggest its dismissal in favour of a fixed reference
      age rendering the use of a health or a disability perspective merely stylistic.

PMID- 19097041
TI  - Equivalence of two healthcare costing methods: bottom-up and top-down.
AB  - This paper compares two quite different approaches to estimating costs: a 'bottom
      up' approach, represented by the US Department of Veterans Affairs' (VA) Decision
      Support System that uses local costs of specific inputs; and a 'top-down'
      approach, represented by the costing system created by the VA Health Economics
      Resource Center, which assigns the VA national healthcare budget to specific
      products using various weighting systems. Total annual costs per patient plus the
      cost for specific services (e.g. clinic visit, radiograph, laboratory, inpatient
      admission) were compared using scatterplots, correlations, mean difference, and
      standard deviation of individual differences. Analysis are based upon 2001 costs
      for 14 915 patients at 72 facilities. Correlations ranged from 0.24 for the cost
      of outpatient encounters to 0.77 for the cost of inpatient admissions, and 0.85
      for total annual cost. The mean difference between costing methods was $707
      ($4168 versus $3461) for total annual cost. The standard deviation of the
      individual differences was $5934. Overall, the agreement between the two costing
      systems varied by the specific cost being measured and increased with
      aggregation. Administrators and researchers conducting cost analyses need to
      carefully consider the purpose, methods, characteristics, strengths, and
      weaknesses when selecting a method for assessing cost.

PMID- 19097042
TI  - Inequity in publicly funded physician care: what is the role of private
      prescription drug insurance?
AB  - This study examines the impact that private financing of prescription drugs in
      Canada has on equity in the utilization of publicly financed physician services.
      The complementary nature of prescription drugs and physician service use
      alongside the reliance on private finance for drugs may induce an income gradient
      in the use of physicians. We use established econometric methods based on
      concentration curves to measure equity in physician utilization and its
      contributors in the province of Ontario. We find that individuals with
      prescription drug insurance make more physician visits than do those without
      insurance, and the effect on utilization is stronger for the likelihood of a
      visit than the conditional number of visits, and stronger for individuals with at
      least one chronic condition than those with no conditions. Results of the equity
      analyses reveal that the most important contributors to the pro-rich inequity in
      physician utilization are income and private prescription drug insurance, while
      public insurance, which covers older people and those on social assistance, has a
      pro-poor effect. These findings highlight that inequity in access to and use of
      publicly funded services may arise from the interaction with privately financed
      health services that are complements to the use of public services.

PMID- 19097043
TI  - Searching for anthropogenic contaminants in human breast adipose tissues using
      gas chromatography-time-of-flight mass spectrometry.
AB  - The potential of gas chromatography-time-of-flight mass spectrometry (GC-TOF MS)
      for screening anthropogenic organic contaminants in human breast adipose tissues
      has been investigated. Initially a target screening was performed for a list of
      125 compounds which included persistent halogen pollutants [organochlorine (OC)
      pesticides, polychlorinated biphenylss (PCBs), polybrominated diphenyl ethers
      (PBDEs)], polyaromatic hydrocarbons (PAHs), alkylphenols, and a notable number of
      pesticides from the different fungicide, herbicide and insecticide families.
      Searching for target pollutants was done by evaluating the presence of up to five
      representative ions for every analyte, all measured at accurate mass (20-mDa mass
      window). The experimental ion abundance ratios were then compared to those of
      reference standards for confirmation. Sample treatment consisted of an extraction
      with hexane and subsequent normal-phase (NP) High performance liquid
      chromatography (HPLC) or SPE cleanup. The fat-free LC fractions were then
      investigated by GC-TOF MS.Full-spectral acquisition and accurate mass data
      generated by GC-TOF MS also allowed the investigation of nontarget compounds
      using appropriate processing software to manage MS data. Identification was
      initially based on library fit using commercial nominal mass libraries. This was
      followed by comparing the experimental accurate masses of the most relevant ions
      with the theoretical exact masses with calculations made using the elemental
      composition calculator included in the software.The application of both target
      and nontarget approaches to around 40 real samples allowed the detection and
      confirmation of several target pollutants including p,p'-DDE, hexachlorobenzene
      (HCB), and some polychlorinated biphenyls (PCBs) and polyaromatic hydrocarbons
      (PAHs). Several nontarget compounds that could be considered anthropogenic
      pollutants were also detected. These included 3,5-di-tert-butyl-4-hydroxy-toluene
      (BHT) and its metabolite 3,5-di-tert-butyl-4-hydroxybenzaldehyde (BHT-CHO),
      dibenzylamine, N-butyl benzenesulfonamide (N-BBSA), some naphthalene-related
      compounds and several PCBs isomers not included in the target list. As some of
      the compounds detected are xenoestrogens, the methodology developed in this paper
      could be useful in human breast cancer research.

PMID- 19097044
TI  - Recent advances in the assessment of the ratios of cortisol to cortisone and of
      some of their metabolites in urine by LC-MS-MS.
AB  - A previously reported method for the assessment of the ratio of
      tetrahydrocortisol (THF) + allo-tetrahydrocortisol (A-THF) to tetrahydrocortisone
      (THE) by HPLC-MS-MS has been significantly improved, in order to increase either
      ruggedness and reliability. That was achieved by the introduction of an on-line
      sample cleanup stage, which made use of a perfusion column as a solid phase
      microextraction (SPE) cartridge. The set of analytes was expanded, by introducing
      cortisol and cortisone, whose ratio supply additional diagnostic information. The
      response factors of both THF and A-THF has been checked, resulting almost
      identical, as well as the influence of the matrix on the calibration curves
      which, although different for water and urine, had similar effect on the ratios
      of interest. As a consequence, the calibration solutions can be prepared in pure
      water. The influence of several different storage procedures has also been
      tested, resulting in no substantial effect on the final result. Finally, the
      improved method has been used to run real samples from healthy volunteers, with
      satisfactory results.

PMID- 19097045
TI  - Comparison of LID versus CID activation modes in tandem mass spectrometry of
      peptides.
AB  - We report our contribution to the systematic investigation of peptide
      fragmentations performed on high-performance Tof equipment, operating in MS and
      MS/MS modes, such as ESI-QqTof and MALDI-Tof/Tof instruments that are commonly
      available today in proteomic laboratories. Whereas the former analyzer's
      configuration provides low-energy collision-induced dissociations (CID), the
      latter allows tunable activation methods of the selected parent ion to induce
      either metastable laser-induced dissociations (LID) or high-energy CID ('gas on
      spectra LID'). Fragmentation of the monoprotonated ion of 53 peptides (FW 807
      2853 g/mol) was undertaken upon low-energy CID on an ESI-QTof mass spectrometer
      (Waters) as well as high-energy CID and LID conditions on a MALDI Ultraflex mass
      spectrometer (Bruker). Systematic comparison of MS/MS spectra provided useful
      information on the performance of each piece of equipment for efficient peptide
      sequencing and also insights into the observed fragmentation behaviors.

PMID- 19097047
TI  - Normal developmental stages of the Madagascar ground gecko Paroedura pictus with
      special reference to limb morphogenesis.
AB  - A table of developmental stages of the target species is useful for studying the
      development of any animal. Although tables of developmental stages have been
      established for several squamates, none has been published for gekkonid lizards.
      We have established a table of developmental stages for the Madagascar ground
      gecko Paroedura pictus. The table includes 27 embryonic stages from oviposition
      to hatching based on chronology and external morphology. The interval from
      oviposition to hatching is 60 days. Eleven to sixteen somites were observed at
      oviposition, and 5 to 6 somites were formed each day. Limb bud swellings were
      recognized by the third day after oviposition. After 2 weeks of incubation, the
      presumptive autopod was detected by carpal/tarsal cartilage formation. Cartilages
      in all digits were seen by 3 weeks after oviposition. Skin pigment was visible
      after 4 weeks incubation, and the skin color pattern was apparent 40 days after
      oviposition.

PMID- 19097049
TI  - Analysis of human muscle stem cells reveals a differentiation-resistant
      progenitor cell population expressing Pax7 capable of self-renewal.
AB  - Studies using mouse models have established a critical role for resident
      satellite stem cells in skeletal muscle development and regeneration, but little
      is known about this paradigm in human muscle. Here, using human muscle stem
      cells, we address their lineage progression, differentiation, migration, and self
      renewal. Isolated human satellite cells expressed alpha7-integrin and other
      definitive muscle markers, were highly motile on laminin substrates and could
      undergo efficient myotube differentiation and myofibrillogenesis. However, only a
      subpopulation of the myoblasts expressed Pax7 and displayed a variable lineage
      progression as measured by desmin and MyoD expression. Analysis identified a
      differentiation-resistant progenitor cell population that was Pax7+/desmin- and
      capable of self-renewal. This study extends our understanding of the role of Pax7
      in regulating human satellite stem cell differentiation and self-renewal.

PMID- 19097048
TI  - Bmp2 is required for cephalic neural tube closure in the mouse.
AB  - BMPs have been shown to play a role in neural tube development particularly as
      dorsalizing factors. To explore the possibility that BMP2 could play a role in
      the developing neural tube (NT) beyond the lethality of Bmp2 null embryos, we
      created Bmp2 chimeras from Bmp2 null ES cells and WT blastocysts. Analysis of
      Bmp2 chimeras reveals NT defects at day 9.5 (E9.5). We found that exclusion of
      Bmp2 null ES cells from the dorsal NT did not always prevent defects. For further
      comparison, we used a Bmp2 mutant line in a mixed background. Phenotypes observed
      were similar to chimeras including open NT defects, postneurulation defects, and
      abnormal neural ectoderm in heterozygous and homozygous null embryos
      demonstrating a pattern of dose-dependent signaling. Our data exposes BMP2 as a
      unique player in the developing NT for dorsal patterning and identity, and normal
      cephalic neural tube closure in a dose-dependent manner.

PMID- 19097051
TI  - Samba, a Xenopus hnRNP expressed in neural and neural crest tissues.
AB  - RNA binding proteins regulate gene expression at the posttranscriptional level
      and play important roles in embryonic development. Here, we report the cloning
      and expression of Samba, a Xenopus hnRNP that is maternally expressed and
      persists at least until tail bud stages. During gastrula stages, Samba is
      enriched in the dorsal regions. Subsequently, its expression is elevated only in
      neural and neural crest tissues. In the latter, Samba expression overlaps with
      that of Slug in migratory neural crest cells. Thereafter, Samba is maintained in
      the neural crest derivatives, as well as other neural tissues, including the
      anterior and posterior neural tube and the eyes. Overexpression of Samba in the
      animal pole leads to defects in neural crest migration and cranial cartilage
      development. Thus, Samba encodes a Xenopus hnRNP that is expressed early in
      neural and neural crest derivatives and may regulate crest cells migratory
      behavior.

PMID- 19097050
TI  - Expression of active Notch1 in avian coronary development.
AB  - Notch1 is an important regulator of intercellular interactions in cardiovascular
      development. We show that the nuclear-localized, cleaved and active form of
      Notch1, the Notch1 intracellular domain (N1ICD), appeared in mesothelial cells of
      the pro-epicardium during epicardial formation at looped heart stages. N1ICD was
      also present in mesothelial cells and mesenchymal cells specifically within the
      epicardium at sulcus regions. N1ICD-positive endothelial cells were detected
      within the nascent vessel plexus at the atrioventricular junction and within the
      compact myocardium (Hamburger and Hamilton stage [HH] 25-HH30). The endothelial
      cells expressing N1ICD were surrounded by N1ICD-positive smooth muscle cells
      after coronary orifice formation (HH32-HH35), while N1ICD expression was absent
      in the mesenchymal and mesothelial cells surrounding mature coronary vessels. We
      propose that differential activation of the hypoxia/HIF1-VEGF-Notch pathway may
      play a role in epicardial cell interactions that promote epicardial
      epithelial/mesenchymal transition and coronary progenitor cell differentiation
      during epicardial development and coronary vasculogenesis in particularly hypoxic
      sulcus regions.

PMID- 19097052
TI  - Introduction to the special issue on cardiac anatomy.

PMID- 19097053
TI  - Sdmg1 is a component of secretory granules in mouse secretory exocrine tissues.
AB  - Sdmg1 is a conserved eukaryotic transmembrane protein that is mainly expressed in
      the gonads where it may have a role in mediating signaling between somatic cells
      and germ cells. In this study we demonstrate that secretory exocrine cells in the
      pancreas, salivary gland, and mammary gland also express Sdmg1. Furthermore, we
      show that Sdmg1 expression is up-regulated during pancreas development when
      regulated secretory granules start to appear, and that Sdmg1 colocalizes with
      secretory granule markers in adult pancreatic acinar cells. In addition, we show
      that Sdmg1 co-purifies with secretory granules during subcellular fractionation
      of the pancreas and that Sdmg1 and the secretory granule marker Vamp2 are
      localized to distinct subdomains in the secretory granule membrane. These data
      suggest that Sdmg1 is a component of regulated secretory granules in exocrine
      secretory cells and that the developmental regulation of Sdmg1 expression is
      related to a role for Sdmg1 in post-Golgi membrane trafficking.

PMID- 19097054
TI  - The embryonic expression patterns and the knockdown phenotypes of zebrafish ADP
      ribosylation factor-like 6 interacting protein gene.
AB  - ADP-ribosylation factor-like 6 (Arl6) mutation is linked to human disease and
      Arl6 interacts with Arl6 interacting protein (Arl6ip). However, the expression
      pattern and function of Arl6ip during embryogenesis are unknown. To confirm
      whether abnormal Arl6ip function might result in embryonic defects in zebrafish,
      we examined the expression patterns of arl6ip during embryogenesis, and they were
      maternally expressed and exhibited in the brain, optic primordia, hypochord,
      spinal cord, myotome, heart, fin-bud, kidney, trunk, and retina. Knockdown of
      Arl6ip revealed the following phenotypic defects: microphthalmia, disorganized
      pigment pattern, flat head, defective tectum, deficient pectoral fins, abnormal
      pneumatic duct, pericardial edema, and deformed trunk. Particularly, histological
      dissection of the retinae of arl6ip-morphants revealed that neuronal
      differentiation is severely delayed, resulting in no formation of retinal layers.
      We further confirmed that opsins of arl6ip-morphants were not transcribed. Based
      on this evidence, Arl6ip may play important roles in zebrafish ocular, heart, and
      fin-bud development.

PMID- 19097055
TI  - Osterix-mCherry transgenic medaka for in vivo imaging of bone formation.
AB  - Intramembranous and chondral bone formation by osteoblasts is found in all
      vertebrates. The genetic network controlling osteoblast differentiation is highly
      conserved and regulated by a small number of key factors, including the zinc
      finger transcription factor Osterix. Expression analysis of osterix in the
      teleost model medaka revealed a highly restricted expression in skeletal regions.
      For in vivo imaging, we generated transgenic medaka expressing mCherry under
      control of the osterix promoter. We show that the transgene becomes expressed in
      early osteoblasts, which have not yet mineralized bone matrix, and remains high
      in matured and mineralizing osteoblasts. Life imaging of transgenic larvae
      provided insight into the appearance and behavior of early osteoblasts during
      development of the teleost cranium, vertebrae, and caudal fin. In summary,
      osterix-mCherry transgenic medaka enable us to analyze osteoblasts during
      different maturation phases in vivo and represent a unique tool to study
      osteoblast behavior in vertebrate embryos and adults.

PMID- 19097058
TI  - Quadriceps muscle reconstruction with free functioning latissimus dorsi muscle
      flap after oncological resection.
AB  - INTRODUCTION: The concept of limb salvage led to increased demand for more
      complex and sophisticated reconstructive options to achieve better functional and
      cosmetic outcome. Reconstruction of the total or partial loss of quadriceps
      muscle after soft tissue sarcomas excision with free functioning latissimus dorsi
      muscle transfer had become more popular in the last years. PATIENTS AND METHODS:
      Between November 1993 and October 2004, 11 patients with average age 45.5 years
      underwent excision of quadriceps muscle followed by simultaneous reconstruction
      with free functioning latissimus dorsi muscle. There were six men and five women.
      The tumors were high grade in 90.9% of patients and were >10 cm in 81.8% of
      patients. The tumor extension required the resection of the entire quadriceps in
      four cases, of three heads in six cases, of only two heads in one case. RESULTS:
      The average follow up was 69 months. The average time of recovery of the
      contractile activity of the muscle was 8.3 months after operation. The
      musculoskeletal tumor society rating score (MTSRS) scored excellent or good in
      73% of patients. Three patients (27.3%) died of metastatic disease. Local
      recurrence occurred in one patient (9.1%). Limb salvage was achieved in all the
      patients (100%). CONCLUSION: This method of reconstruction is a reliable
      technique not only to fill the defect resulting from oncological resection but
      also to provide better function. Microsurgical reconstruction of soft tissue
      sarcoma helps to expand the indications of limb salvage by allowing better local
      control and achieving adequate function and coverage.

PMID- 19097059
TI  - Saphenous vein grafts for perforator flap salvage in autologous breast
      reconstruction.
AB  - Although the use of saphenous vein grafts in free-flap salvage and extremity
      replantation is relatively common, their use in breast reconstruction is rare.
      These two case reports represent extreme alternatives for breast reconstruction
      flap salvage. In our normal daily practice, the overwhelming majority of elective
      breast reconstructions proceed smoothly. However, the occasional patient may
      require saphenous vein graft flap rescue for completion of the reconstruction.

PMID- 19097060
TI  - Resurfacing of a complex upper extremity injury: an excellent indication for the
      dorsal thoracic fascial flap.
AB  - We report a case of a 24-year-old patient who sustained a mutilating crush injury
      to the left forearm. After thorough debridement and stabilization of the skeletal
      injury, the dorsal thoracic fascial flap was used to resurface the
      circumferential wound, protect the underlying structures, and provide a gliding
      surface for the exposed tendons. The flap was safely transected during revision
      surgery, and at 6-months follow-up, excellent functional and cosmetic results
      were achieved. The dorsal thoracic fascia is a thin, durable, and pliable tissue
      that is based on a long vascular pedicle. We consider the dorsal thoracic fascial
      flap as a valuable option for coverage of complex upper extremity injuries and
      highly recommend its use.

PMID- 19097061
TI  - Transfer of the second to the first metatarsal ray in a case of lawn mower
      injury: a case report.
AB  - The medial longitudinal arch of the foot plays a major role for a physiologic
      transfer of the load from the heel to the forefoot during walking and running.
      Traumatic amputation that involve either the great toe or the whole first
      metatarsal bone can lead to collapse of the medial longitudinal arch, overload of
      the metatarsal heads, and painful callus formation. If replant of the amputated
      part is not possible or has failed, it is advisable to reconstruct the medial
      longitudinal arch in order to re-establish a functional transfer of the load in
      the foot. We present a case of a young lady who suffered from traumatic
      amputation at the distal third of the first metatarsal. Replantation failed due
      to the severity of the initial injury. Despite a good coverage of the defect with
      a lateral arm flap, the patient developed a painful plantar callus underneath the
      amputated stump. The adjacent second metatarsal ray was then raised as a pedicled
      flap including bone and soft tissues and transferred to the first ray in order to
      reconstruct a physiologic medial longitudinal arch. The patient had excellent
      functional results with no recurrence of the callus.

PMID- 19097062
TI  - The normal and abnormal anatomy of the coronary arteries.
AB  - Beneficial therapeutic options are increasingly available for coronary arterial
      disease. To take full advantage of these options, those performing the
      interventions require a thorough knowledge of the normal arrangement, and likely
      anatomic variations, of the coronary arterial system. A comprehensive
      appreciation of the architecture of the coronary arterial system, therefore, is
      crucial to optimal cardiac care. Simple attention to potential variations in the
      origin and course of the major coronary arteries can greatly enhance clinical
      outcomes. The objective of this review, therefore, is to describe the normal
      anatomical distribution of the coronary arteries in the human heart, and to list
      the most common arterial variations.

PMID- 19097063
TI  - Cardiac veins: a review of the literature.
AB  - Cardiac veins have long stood in the shadow of their more extensively studied
      counterparts, the coronary arteries. The clinical importance of the coronary
      venous system, nonetheless, should not be underestimated. Intricate and
      beneficial therapeutic options are increasingly being developed that depend on
      knowledge of the structure of this venous network. Such interventions have been
      shown greatly to promote cardiac health, and to enhance the efficacy of cardiac
      pacing. A comprehensive appreciation of the architecture of the coronary venous
      system, therefore, is crucial to optimal cardiac care. It is possible to provide
      an overview of the arrangement of the cardiac veins, with the larger veins
      draining to the coronary sinus, and thence to the right atrium, but with smaller
      and minimal veins draining directly to the cavities of the atrial chambers. The
      venous pathways, nonetheless, are highly variable, making exceptions the commonly
      accepted rule. As such, unique solutions for imaging, and simple attentiveness to
      possible venous variations, can greatly enhance clinical outcomes. For example,
      identifying the diameter, course, and valves of the cardiac veins allows for
      anticipation of impediments during interventional procedures, and allows for
      informed clinical decision-making. Also of significance is awareness of alternate
      arrangements that may be encountered in terms of venous drainage, and the
      importance of intramural venous collecting spaces in these patterns. The
      objective of our review, therefore, is to explore and describe the anatomical
      distribution of the coronary veins.

PMID- 19097064
TI  - The clinical anatomy of the coronary collateral circulation.
AB  - Although the structure and function of the coronary vasculature has been
      exhaustively studied, it still holds significant elements of mystery for the
      researcher and clinician. This is particularly true regarding the structure and
      function of the human collateral coronary circulation. Controversy still exists
      concerning the pathways of collateral vessels as well as their function.
      Controversies also exist relative to the methods used to delineate the pathways,
      these being additionally compounded by the lack of standardization of the studies
      and measurements. In this review, we summarize our current knowledge of this
      functionally significant vascular network.

PMID- 19097065
TI  - The polyamine analogue N1,N11-diethylnorspermine can induce chondrocyte apoptosis
      independently of its ability to alter metabolism and levels of natural
      polyamines.
AB  - We have been investigating the effects of natural polyamines and polyamine
      analogues on the survival and apoptosis of chondrocytes, which are cells critical
      for cartilage integrity. Treatment of human C-28/I2 chondrocytes with N(1),N(11)
      diethylnorspermine (DENSPM), a polyamine analogue with clinical relevance as an
      experimental anticancer agent, rapidly induced spermidine/spermine N(1)
      acetyltransferase (SSAT) and spermine oxidase (SMO), key enzymes of polyamine
      catabolism and down-regulated ornithine decarboxylase, the first enzyme of
      polyamine biosynthesis, thus depleting all main polyamines within 24 h. The
      treatment with DENSPM did not provoke cell death and caspase activation when
      given alone for 24 h, but caused a caspase-3 and -9 dependent apoptosis in
      chondrocytes further exposed to cycloheximide (CHX). In other cellular models,
      enhanced polyamine catabolism or polyamine depletion has been implicated as
      mechanisms involved in DENSPM-related apoptosis. However, the simultaneous
      addition of DENSPM and CHX rapidly increased caspase activity in C-28/I2 cells in
      the absence of SSAT and SMO induction or significant reduction of polyamine
      levels. Moreover, caspase activation induced by DENSPM plus CHX was not prevented
      by a N(1)-acetylpolyamine oxidase (PAO)/SMO inhibitor, and depletion of all
      polyamines obtained by specific inhibitors of polyamine biosynthesis did not
      reproduce DENSPM effects in the presence of CHX. DENSPM/CHX-induced apoptosis was
      associated with changes in the amount or activation of signalling kinases, Akt
      and MAPKs, and increased uptake of DENSPM. In conclusion, the results suggest
      that DENSPM can favour apoptosis in chondrocytes independently of its effects on
      polyamine metabolism and levels.

PMID- 19097066
TI  - The involvement of Ca2+ and integrins in directional responses of zebrafish
      keratocytes to electric fields.
AB  - Many cells respond directionally to small DC electrical fields (EFs) by an
      unknown mechanism, but changes in intracellular Ca(2+) are widely assumed to be
      involved. We have used zebrafish (Danio rerio) keratocytes in an effort to
      understand the nature of the EF-cell interaction. We find that the adult
      zebrafish integument drives substantial currents outward through wounds produced
      by scale removal, establishing that keratocytes near the wound will experience
      endogenous EFs. Isolated keratocytes in culture turn toward the cathode in fields
      as small as 7 mV mm(-1), and the response is independent of cell size. Epidermal
      sheets are similarly sensitive. The frequency of intracellular Ca(2+) spikes and
      basal Ca(2+) levels were increased by EFs, but the spikes were not a necessary
      aspect of migration or EF response. Two-photon imaging failed to detect a pattern
      of gradients of Ca(2+) across the lamellipodia during normal or EF-induced
      turning but did detect a sharp, stable Ca(2+) gradient at the junction of the
      lamellipodium and the cell body. We conclude that gradients of Ca(2+) within the
      lamellipodium are not required for the EF response. Immunostaining revealed an
      anode to cathode gradient of integrin beta1 during EF-induced turning, and
      interference with integrin function attenuated the EF response. Neither
      electrophoretic redistribution of membrane proteins nor asymmetric perturbations
      of the membrane potential appear to be involved in the EF response, and we
      propose a new model in which hydrodynamic forces generated by electro-osmotic
      water flow mediate EF-cell interactions via effects on focal adhesions.

PMID- 19097067
TI  - Negative modulation of eNOS by laminin involving post-translational
      phosphorylation.
AB  - Nitric oxide (NO) regulates the vascular tone, and influences survival and
      apoptosis of endothelial cells (ECs). NO is produced by nitric oxide synthase
      (NOS) and eNOS is the constitutive enzyme in the endothelium. Though the
      extracellular matrix (ECM) has been reported to regulate various EC functions,
      the role of ECM in the regulation of eNOS is not clear. The present study was
      designed to analyze if laminin-1 (Ln-1), the major glycoprotein of the basement
      membrane, can regulate eNOS. The activity of eNOS was significantly low in ECs
      maintained on Ln-1 as compared to those on Col I and polylysine. Reversal of the
      effect of Ln-1 on treatment with inhibitor of p38 MAPK and changes in Thr and Ser
      phosphorylation in purified eNOS suggested that eNOS activity in cells maintained
      on Ln-1 is negatively regulated by post-translational phosphorylation at Ser and
      Thr residues by recruiting p38 MAPK pathway. Increase in eNOS activity and
      induction of apoptosis upon inhibition of p38 MAPK and reversal of this on
      inhibition of NOS by L-NAME suggested that increased NO induced apoptosis in ECs
      maintained on Ln-1 when p38 MAPK was inhibited. These results suggest that Ln
      contributes to survival of ECs by negatively modulating eNOS in a p38 MAPK
      dependent pathway.

PMID- 19097068
TI  - The extracellular matrix protein TGFBI promotes myofibril bundling and muscle
      fibre growth in the zebrafish embryo.
AB  - The extracellular matrix protein Tgfbi has been shown to localise to myotendinous
      junctions in mouse and postulated to interact with the transmembrane protein
      Integrin alpha7beta1, which, in parallel with the Dystrophin-associated protein
      complex, is critical for linkage between the extracellular matrix and the
      cytoskeleton of muscle fibres. Here we use a GFP-tagged form of Tgfbi to analyse
      its distribution in the developing skeletal muscle of the zebrafish embryos and
      antisense morpholino oligonucleotides to investigate the function of the
      endogenous protein. We find that although tagged Tgfbi accumulates at the
      myosepta, the attachment of muscle fibres to the myosepta is established and
      maintained normally in morphant embryos; however, the fibres show a marked
      reduction in their growth and a disruption of their myofibril bundles.

PMID- 19097069
TI  - Cytokine signalling by gp130 regulates gastric mucosal healing after ulceration
      and, indirectly, antral tumour progression.
AB  - The cytokines IL-6 and IL-11, which signal via the receptor gp130, have been
      implicated in various gut pathologies, including inflammation and wound healing.
      We used mouse cytokine signalling mutants to evaluate the role of gp130 pathways
      in gastric ulceration and healing and the effect of spatially remote fundic
      ulceration on antral tumour progression, since compromised wound healing may
      impact tumourigenesis. Glacial acetic acid applied to the serosal surface of
      stomachs from wild-type, gp130(757FF), IL-6(-/-) and IL-11 receptor (R)alpha(-/-)
      mice was used to induce discrete haemostasis/necrosis and resultant mucosal
      ulceration. Wound pathology and mRNA expression of key cytokine target genes were
      examined 2 and 14 weeks after ulcer induction. The outcome of fundic ulceration
      on antral tumour development in gp130(757FF) mice was also examined. Chemical
      haemostasis in gp130(7575FF) mice produces more severe gastric ulcers than in
      wild-type mice. Lack of IL-6 produces more severe ulceration, while loss of IL
      11Ralpha less severe ulcers, suggesting a role for IL-11 in ulcer induction.
      Increased expression of ulcer-associated IL-11 and its established mitogenic
      target genes RegI, IIIbeta and IIIgamma paralleled severe ulceration in
      gp130(757FF) mice. In this model, coincident with fundic ulceration, antral
      tumour development was inhibited and correlated with decreased RegI, IIIbeta and
      IIIgamma and reduced MMP9 and 13 expression. IL-11-driven transcription via gp130
      contributes to the gastric mucosal response to ulceration. Fundic mucosal
      ulceration modulates antral growth factor and metalloproteinase gene expression,
      thereby contributing to restricted tumour growth.

PMID- 19097070
TI  - A copy number gain of the 6p arm is linked with advanced hepatocellular
      carcinoma: an array-based comparative genomic hybridization study.
AB  - In accordance with cancer progression, genomic aberrations accumulate in cancer
      cells in a stepwise fashion. However, whether there are genomic changes linked
      with tumour progression remains unclarified. The purpose of this study is to
      elucidate the relationship between genomic alterations and clinical stages in
      hepatocellular carcinoma (HCC). A technology of array-based CGH using DNA chips
      spotted with 1440 BAC clones was applied to 42 surgically removed HCCs to examine
      the DNA copy number aberrations. A frequent copy number gain was detected on
      chromosomal regions 1q, 8q and Xq. In particular, gains of 1q42.12, 1q43 and
      8q24.3 were detected in more than 65% of tumours. A frequent copy number loss was
      detected on chromosomal regions 1p, 4q, 6q, 8p and 17p. Losses of 8p21 and 17p13
      were detected in more than 55% of HCCs. However, the DNA copy number gains of
      clones on 6p and 8q24.12 were more frequent in stage III/IV tumours than in stage
      I/II tumours (p < 0.001). In particular, the gain of the whole 6p was virtually
      limited to advanced-staged HCCs. The gain of the whole 6p is suggested to be a
      genomic marker for the late stages in HCCs. These observations therefore support
      the concept of genomic staging in HCC.

PMID- 19097071
TI  - Defective activations of STAT3 Ser727 and PKC isoforms lead to oncostatin M
      resistance in metastatic melanoma cells.
AB  - Stage III melanoma is refractory to common therapies and shows resistance to the
      anti-proliferative activity of cytokines in vitro. We previously demonstrated
      that, for 30% of the metastatic melanoma cell lines, oncostatin M (OSM)
      resistance is due to the epigenetic silencing of its receptor OSMRbeta. Here we
      analyse, on a larger panel of short-term cultures derived from melanoma-invaded
      lymph nodes, other mechanisms potentially implicated in OSM resistance. For 18%
      of the cell lines, OSM resistance is associated with a phosphorylation defect of
      signal transducer and activator of transcription (STAT)3 on serine (Ser)727, in
      concordance with defects in the activation of various protein kinase C (PKC)
      isoforms, especially PKCdelta. For 21% of the cell lines, OSM resistance is
      associated with a defect in the activation of Akt on Ser473. By the use of
      inhibitors, dominant negatives and small interfering (si)RNA, we show that the
      PKC-STAT3 Ser727, but not the Akt, pathway appears necessary for OSM anti
      proliferative activity. Moreover, we bring evidence that OSM or interleukin (IL)
      6, produced in lymph nodes and/or melanoma cells, could be involved in the
      establishment of OSM resistance during melanoma progression. These findings could
      be relevant for the prognosis and the treatment of stage III melanoma patients.

PMID- 19097076
TI  - Using theory and experiment to discover catalysts for electrocyclizations.

PMID- 19097072
TI  - Muscle degeneration and leukocyte infiltration caused by mutation of zebrafish
      Fad24.
AB  - Factor for adipocyte differentiation 24 (fad24) is a novel gene that has been
      implicated in adipocyte differentiation and DNA replication. In a screen for
      zebrafish mutants that have an abnormal tissue distribution of neutrophils, we
      identified an insertional allele of fad24, fad24hi1019. Homozygous fad24hi1019
      larvae exhibit muscle degeneration accompanied by leukocyte infiltration. Muscle
      degeneration was extensive and included tissue apoptosis and disorganized, poorly
      striated muscle fibers. Blocking apoptosis using pan-caspase inhibitors resulted
      in decreased neutrophil recruitment into the body of the larva, suggesting a
      causative link between apoptosis and leukocyte infiltration. These findings
      suggest that zebrafish is a powerful genetic model system to address the
      interplay between muscle degeneration and leukocyte infiltration, and indicate
      that tissue apoptosis may contribute to neutrophil recruitment in some
      inflammatory states.

PMID- 19097077
TI  - Combination of Mn(2+)-enhanced and diffusion tensor MR imaging gives
      complementary information about injury and regeneration in the adult rat optic
      nerve.
AB  - PURPOSE: To evaluate manganese (Mn(2+))-enhanced MRI (MEMRI) and diffusion tensor
      imaging (DTI) as tools for detection of axonal injury and regeneration after
      intravitreal peripheral nerve graft (PNG) implantation in the rat optic nerve
      (ON). MATERIALS AND METHODS: In adult Fischer rats, retinal ganglion cell (RGC)
      survival was evaluated in Flurogold (FG) back-filled retinal whole mounts after
      ON crush (ONC), intravitreal PNG, and intravitreal MnCl(2) injection (150 nmol)
      at 0 and 20 days post lesion (dpl). MEMRI and echo-planar DTI (DTI-EPI) was
      obtained of noninjured ON one day after intravitreal MnCl(2) injection, and at 1
      and 21 dpl after ONC, intravitreal PNG, and intravitreal MnCl(2) injections given
      at 0 and 20 dpl. GAP-43 immunohistochemistry was performed after the last MRI.
      RESULTS: ONC reduced RGC density in retina by 94% at 21 dpl compared to
      noninjured ON without MnCl(2) injections. Both intravitreal PNG and intravitreal
      MnCl(2) injections improved RGC survival in retina, which was reduced by 90%
      (ONC+MnCl(2)), 82% (ONC+PNG), and 74% (ONC+PNG+MnCl(2)) compared to noninjured
      ON. DTI-derived parameters (fractional anisotropy [FA], mean diffusivity, axial
      diffusivity lambda( parallel), and radial diffusivity lambda( perpendicular))
      were unaffected by the presence of Mn(2+) in the ON. At 1 dpl, CNR(MEMRI) and
      lambda( parallel) were reduced at the injury site, while at 21 dpl they were
      increased at the injury site compared to values measured at 1 dpl. GAP-43
      immunoreactive axons were present in the ON distal to the ONC injury site.
      CONCLUSION: MEMRI and DTI enabled detection of functional and structural
      degradation after rat ON injury, and there was correlation between the MRI
      derived and immunohistochemical measures of axon regeneration.

PMID- 19097078
TI  - Novel technique used to detect swallowing in volume-selective turbo spin-echo
      (TSE) for carotid artery wall imaging.
AB  - PURPOSE: To improve three-dimensional (3D) volume-selective turbo spin-echo (TSE)
      carotid wall imaging by the addition of a novel body surface swallowing detection
      device. MATERIAL AND METHODS: A 3D volume-selective TSE sequence was used to
      image the carotid artery. A novel carbon-fiber motion device, positioned over the
      laryngeal prominence, was used to detect swallowing movement. An electrical
      output generated by coil movement was used to detect motion, and an algorithm was
      programmed to reject data acquired during swallowing and for a short period
      afterwards. Images were acquired with and without the algorithm and scored on a
      scale of 0-5 by four independent blinded observers according to the clarity of
      the vessel wall, e.g., 0 = poor image quality and 5 = excellent quality images
      with little or no artifact. RESULTS: The scans with the rejection algorithm on
      were scored higher than the scans without the algorithm. The comparison of scores
      with the algorithm on vs. the algorithm off were as follows: mean +/- standard
      deviation (SD) = 3.76 +/- 0.25, 95% confidence interval (CI) = 3.27-4.25 vs. 2.64
      +/- 0.25, 95% CI = 2.15-3.13; with good interobserver correlation (Kendall's W
      score 0.77). CONCLUSION: Image quality can be improved by the algorithm during
      acquisition. This can be achieved by a novel, anatomically positioned superficial
      device. This may help in prolonged 3D scans where a single movement can corrupt
      the entire acquisition.

PMID- 19097079
TI  - Safety of ferucarbotran in MR imaging of the liver: a pre- and postexamination
      questionnaire-based multicenter investigation.
AB  - PURPOSE: To prospectively investigate, by means of a pre-and postexamination
      questionnaire, the types and frequency of adverse reactions to ferucarbotran
      (Resovist), a superparamagnetic iron oxide (SPIO) contrast agent. MATERIALS AND
      METHODS: This study was approved by the ethics committee of each of the
      institutions involved, and all patients gave written informed consent. One
      questionnaire asking about baseline symptoms before the injection of
      ferucarbotran, and one about adverse events over a period of seven days after
      injection were given to 315 patients who underwent ferucarbotran-enhanced
      magnetic resonance imaging (MRI) of the liver at several institutions. The data
      for baseline symptoms were used for reference to exclude false-positive adverse
      reactions and were also compared with the adverse event data to determine with
      McNemar's chi-squared test the incidence of each symptom. RESULTS: Before MR
      examination, 249 clinical symptoms were reported by 102 of 315 patients (32.4%).
      After the injection of ferucarbotran, 169 adverse events were observed in 78
      patients (24.8%). Eventually, 70 adverse events occurring in 45 patients (14.3%)
      were judged to be adverse reactions to ferucarbotran, defined as possibly or
      definitely ferucarbotran-related events. All reactions were of mild intensity.
      CONCLUSION: Ferucarbotran can be considered safe for clinical use in liver MRI.

PMID- 19097080
TI  - New coil positioning method for interleaved transcranial magnetic stimulation
      (TMS)/functional MRI (fMRI) and its validation in a motor cortex study.
AB  - PURPOSE: To develop and test a novel method for coil placement in interleaved
      transcranial magnetic stimulation (TMS)/functional MRI (fMRI) studies. MATERIALS
      AND METHODS: Initially, a desired TMS coil position at the subject's head is
      recorded using a neuronavigation system. Subsequently, a custom-made holding
      device is used for coil placement inside the MR scanner. The parameters of the
      device corresponding to the prerecorded position are automatically determined
      from a fast structural image acquired directly before the experiment. The spatial
      accuracy of our method was verified on a phantom. Finally, in a study on five
      subjects, the coil was placed above the cortical representation of a hand muscle
      in M1 and the blood oxygenation level-dependent (BOLD) responses to short
      repetitive TMS (rTMS) trains were assessed using echo-planar imaging (EPI)
      recordings. RESULTS: The spatial accuracy of our method is in the range of 2.9 +/
      1.3 (SD) mm. Motor cortex stimulation resulted in robust BOLD activations in
      motor- and auditory related brain areas, with the activation in M1 being
      localized in the hand knob. CONCLUSION: We present a user-friendly method for TMS
      coil positioning in the MR scanner that exhibits good spatial accuracy and speeds
      up the setup of the experiment. The motor-cortex study proves the viability of
      the approach and validates our interleaved TMS/fMRI setup.

PMID- 19097081
TI  - Factors that distinguish serious versus less severe strain and sprain injuries:
      an analysis of electric utility workers.
AB  - BACKGROUND: Occupational sprain and strain injuries are one of the most common
      types of nonfatal occupational injuries and a significant source of lost
      workdays. This study examines factors associated with severe work-related
      sprain/strain injuries to the back, shoulder, and knees. METHODS: A synthetic
      case-control study was performed (controls were selected from the same pool of
      utility workers as cases). Cases included all electric utility workers who had
      experienced a severe work-related sprain/strain injury to the back, knee, or
      shoulder. Primary controls were selected from all workers who had sustained a
      minor injury. Secondary controls were selected from employees with a minor
      sprain/strain injury to the back, knee, or shoulder. Multivariate logistic
      regression models were used to estimate odds ratios and 95% confidence intervals.
      RESULTS: Workers 41 years and older were more likely to have experienced severe
      shoulder sprain/strain injuries [Age 41-50: OR = 3.62, 95% CI: 1.71-7.65; age 51
      and older: OR = 4.49, 95% CI: 1.89-10.67] and severe back sprain/strain injuries
      [Age 41-50: OR = 1.70, 95% CI: 1.06-2.33; age 51 and older: OR = 1.5, 95% CI:
      0.90-2.52]. Line workers and maintenance workers had an increased risk of serious
      sprain/strain injuries. Gender and day of week were not significantly associated
      with sprain/strain injuries. DISCUSSION: Though this study is limited by
      available data, future studies may benefit from this preliminary examination of
      occupational and demographic characteristics associated with serious
      sprain/strain injuries among electric utility workers.

PMID- 19097082
TI  - Estimation of health-care costs for work-related injuries in the Mexican
      Institute of Social Security.
AB  - BACKGROUND: Data on the economic consequences of occupational injuries is scarce
      in developing countries which prevents the recognition of their economic and
      social consequences. This study assess the direct heath care costs of work
      related accidents in the Mexican Institute of Social Security, the largest health
      care institution in Latin America, which covered 12,735,856 workers and their
      families in 2005. METHODS: We estimated the cost of treatment for 295,594
      officially reported occupational injuries nation wide. A group of medical experts
      devised treatment algorithms to quantify resource utilization for occupational
      injuries to which unit costs were applied. Total costs were estimated as the
      product of the cost per illness and the severity weighted incidence of
      occupational accidents. RESULTS: Occupational injury rate was 2.9 per 100
      workers. Average medical care cost per case was $2,059 USD. The total cost of the
      health care of officially recognized injured workers was $753,420,222 USD. If
      injury rate is corrected for underreporting, the cost for formal injured workers
      is 791,216,460. If the same costs are applied for informal workers, approximately
      half of the working population in Mexico, the cost of healthcare for occupational
      injuries is about 1% of the gross domestic product. CONCLUSIONS: Health care
      costs of occupational accidents are similar to the economic direct expenditures
      to compensate death and disability in the social security system in Mexico.
      However, indirect costs might be as important as direct costs.

PMID- 19097083
TI  - A case of generalized argyria after ingestion of colloidal silver solution.
AB  - A 58-year-old woman was referred to our hospital due to progressive skin
      darkening, which began 5 months previously. The patient had strikingly diffuse
      blue-gray discoloration of the skin, most prominent in sun-exposed areas,
      especially her face and hands. The oral mucosa, tongue, gums, eye conjunctiva,
      ears, nail beds, and trunk were also involved. Bluish-gray discoloration of all
      nails was aggravated by cold weather. She had ingested 1 L of colloidal silver
      solution daily for approximately 16 months as a traditional remedy. Her serum
      silver concentration was 381 ng/ml which was a very high (reference level: <15
      ng/ml). Light microscopic examination of a punch biopsy specimen from her nose
      revealed fine, minute, round, and brown-black granules deposited in the basement
      membrane of hair follicular epithelium. Scanning electron microscopic examination
      showed electron-dense granules deposited in the intercellular space of sweat
      glands. Energy disperse X-ray spectrometry analysis demonstrated peaks for silver
      and sulfur in the dense black deposits. The ingestion of colloidal silver appears
      to be an increasing practice among patients using alternative health practices.
      All silver-containing products including colloidal silver should be labeled with
      a clear warning to prevent argyria, especially in alternative health practices.

PMID- 19097084
TI  - Direct and tumor microenvironment mediated influences of 5'-deoxy-5'
      (methylthio)adenosine on tumor progression of malignant melanoma.
AB  - Recent studies have shown that a loss of methylthioadenosine phosphorylase (MTAP)
      gene expression exerts a tumor-promoting effect, including induction of
      invasiveness, enhanced cell proliferation, and resistance against cytokines. To
      date, the molecular mechanisms underlying these effects remain unknown. Since the
      loss of MTAP expression resulted in induced secretion of 5'-deoxy-5'
      (methylthio)adenosine (MTA), we hypothesized that MTA might modulate the observed
      effects. We first determined MTA levels produced by tumor cells in vitro and in
      situ by means of stable isotope dilution liquid chromatography tandem mass
      spectrometry. Subsequently, we revealed induction of matrix metalloproteinase
      (MMP) and growth factor gene expression in melanoma cells accompanied by enhanced
      invasion and vasculogenic mimicry. In addition, MTA induced the secretion of
      basis fibroblast growth factor (bFGF) and MMP3 from fibroblasts and the
      upregulation of activator protein-1 (AP-1) activity in melanoma cells and
      fibroblasts. In summary, we demonstrated a tumor-supporting role of MTA.

PMID- 19097089
TI  - Zinc-finger paralogues tsh and tio are functionally equivalent during imaginal
      development in Drosophila and maintain their expression levels through auto- and
      cross-negative feedback loops.
AB  - teashirt (tsh) and tiptop (tio) are two Drosophila gene paralogues encoding zinc
      finger transcription factors. While tsh is an important developmental regulator,
      tio null individuals are viable and fertile. Here, we show that tio and tsh have
      coincident expression domains in the imaginal discs, the precursors of the adult
      body, and that both genes show similar functional properties when expressed
      ectopically. Furthermore, tio is able to rescue the development of tsh mutants,
      indicating that both genes are functionally equivalent during imaginal
      development. Of interest, the transcriptional regulation of tio and tsh is linked
      by a negative feedback loop. This mechanism might be required to maintain a tight
      control on the total levels of tio/tsh and could help explaining why Drosophila
      keeps an apparently dispensable gene.

PMID- 19097085
TI  - Transplantation of human embryonic stem cell-derived endothelial cells for
      vascular diseases.
AB  - Using endothelial cells for therapeutic angiogenesis/vasculogenesis of ischemia
      diseases has led to exploring human embryonic stem cells (hESCs) as a potentially
      unlimited source for endothelial progenitor cells. With their capacity for self
      renewal and pluripotency, hESCs and their derived endothelial cells (hESC-ECs)
      may be more advantageous than other endothelial cells obtained from diseased
      populations. However, hESC-ECs' poor differentiation efficiency and poorly
      characterized in vivo function after transplantation present significant
      challenges for their future clinical application. This review will focus on the
      differentiation pathways of hESCs and their therapeutic potential for vascular
      diseases, as well as the monitoring of transplanted cells' fate via molecular
      imaging. Finally, cell enhancement strategies to improve the engraftment
      efficiency of hESC-ECs will be discussed.

PMID- 19097090
TI  - Multicompartmental analysis of late contrast enhancement in areas of myocardial
      infarction supplied by chronically occluded coronary arteries.
AB  - PURPOSE: To analyze the relationship between late contrast enhancement (LCE) and
      the interstitial distribution volume (V(In)) of gadolinium (Gd) tracers in the
      myocardial infarction (MI) areas supplied by chronically occluded arteries from
      patients. In animal experimental models, LCE has already been shown to correspond
      to an enhanced V(In) of Gd tracers and thus, to a decrease in the amount of
      intact cells. MATERIALS AND METHODS: A multicompartmental analysis was applied to
      serial MRI images encompassing both infarct and remote areas and recorded with a
      conventional two-dimensional (2D) segmented inversion-recovery gradient-echo (IR
      GRE) sequence during a 15-minute period following Gd-diethylenetriamine
      pentaacetic acid (Gd-DTPA) injection in 12 patients with Q-wave MI supplied by
      chronically occluded coronary arteries. RESULTS: V(In) from infarct tissue was:
      1) higher than V(In) from remote areas (in % of myocardial volume: 74 +/- 16% vs.
      20 +/- 7%, P < 0.001); and 2) correlated with the quantification of LCE between
      infarct and noninfarct areas at the 15th minute (R(2) = 0.63, P = 0.002).
      However, the difference in V(In) between infarct and remote myocardium was a much
      better correlate of this quantified LCE (R(2) = 0.85, P < 0.001). CONCLUSION:
      Detection of LCE in the MI territories supplied by chronically occluded arteries
      relates to the difference in the V(In) of tracers between the infarct and the
      noninfarct areas.

PMID- 19097091
TI  - Fast 3D (1)H MRSI of the corticospinal tract in pediatric brain.
AB  - PURPOSE: To develop a (1)H magnetic resonance spectroscopic imaging (MRSI)
      sequence that can be used to image infants/children at 3T and by combining it
      with diffusion tensor imaging (DTI) tractography, extract relevant metabolic
      information corresponding to the corticospinal tract (CST). MATERIALS AND
      METHODS: A fast 3D MRSI sequence was developed for pediatric neuroimaging at 3T
      using spiral k-space readout and dual band RF pulses (32 x 32 x 8 cm field of
      view [FOV], 1 cc iso-resolution, TR/TE = 1500/130, 6:24 minute scan). Using DTI
      tractography to identify the motor tracts, spectra were extracted from the CSTs
      and quantified. Initial data from infants/children with suspected motor delay (n
      = 5) and age-matched controls (n = 3) were collected and N-acetylaspartate (NAA)
      ratios were quantified. RESULTS: The average signal-to-noise ratio of the NAA
      peak from the studies was approximately 22. Metabolite profiles were successfully
      acquired from the CST by using DTI tractography. Decreased NAA ratios in those
      with motor delay compared to controls of approximately 10% at the CST were
      observed. CONCLUSION: A fast and robust 3D MRSI technique targeted for pediatric
      neuroimaging has been developed. By combining with DTI tractography, metabolic
      information from the CSTs can be retrieved and estimated. By combining DTI and 3D
      MRSI, spectral information from various tracts can be obtained and processed.

PMID- 19097092
TI  - Susceptibility compensated fMRI study using a tailored RF echo planar imaging
      sequence.
AB  - PURPOSE: To implement a method using a tailored radiofrequency (TRF) pulse with a
      quadratic phase profile to recover susceptibility-induced signal losses in
      gradient-recalled echo-planar images (EPI). MATERIALS AND METHODS: A functional
      magnetic resonance imaging (fMRI) experiment for compensation of susceptibility
      artifacts, known as the TRF pulse EPI sequence (TRF-EPI), was used. TRF pulse
      compensates the susceptibility effect with a reduced signal-to-noise ratio (SNR)
      to one-half when the maximum phase distribution is 2pi. We demonstrate
      theoretically that the maximum phase distribution can also be reduced to pi
      rather than 2pi, improving the SNR accordingly. An analysis was conducted
      comparing this newly proposed strategy using a standard RF excitation with a
      linear phase distribution and a quadratic TRF excitation with a pi phase
      distribution. RESULTS: Thorough experimental comparisons were also made between
      the TRF quadratic excitation with a pi phase profile and conventional EPI with a
      standard excitation in human subjects during ventral brain activation.
      CONCLUSION: With reduced maximum phase distribution in the TRF pulse, signals in
      the susceptibility-affected areas, such as the orbitofrontal and inferior
      temporal cortex, were increased, suggesting that the technique could be a useful
      adjunct to fMRI.

PMID- 19097093
TI  - 3D coronary motion tracking in swine models with MR tracking catheters.
AB  - PURPOSE: To develop MR-tracked catheters to delineate the three-dimensional
      motion of coronary arteries at high spatial and temporal resolution. MATERIALS
      AND METHODS: Catheters with three tracking microcoils were placed into nine
      swine. During breath-holds, electrocardiographic (ECG)-synchronized 3D motion was
      measured at varying vessel depths. 3D motion was measured in American Heart
      Association left anterior descending (LAD) segments 6-7, left circumflex (LCX)
      segments 11-15, and right coronary artery (RCA) segments 2-3, at 60-115 beats/min
      heart rates. Similar-length cardiac cycles were averaged. Intercoil cross
      correlation identified early systolic phase (ES) and determined segment motion
      delay. RESULTS: Translational and rotational motion, as a function of cardiac
      phase, is shown, with directionality and amplitude varying along the vessel
      length. Rotation (peak-to-peak solid-angle RCA approximately 0.10, LAD
      approximately 0.06, LCX approximately 0.18 radian) occurs primarily during fast
      translational motion and increases distally. LCX displacement increases with
      heart rate by 18%. Phantom simulations of motion effects on high-resolution
      images, using RCA results, show artifacts due to translation and rotation.
      CONCLUSION: Magnetic resonance imaging (MRI) tracking catheters quantify motion
      at 20 fps and 1 mm(3) resolution at multiple vessel depths, exceeding that
      available with other techniques. Imaging artifacts due to rotation are
      demonstrated. Motion-tracking catheters may provide physiological information
      during interventions and improve imaging spatial resolution.

PMID- 19097095
TI  - Three-dimensional dynamic time-resolved contrast-enhanced MRA using parallel
      imaging and a variable rate k-space sampling strategy in intracranial
      arteriovenous malformations.
AB  - PURPOSE: To evaluate the effectiveness of three-dimensional (3D) dynamic time
      resolved contrast-enhanced MRA (TR-CE-MRA) using a combination of a parallel
      imaging technique (ASSET: array spatial sensitivity encoding technique) and a
      time-resolved method (TRICKS: time-resolved imaging of contrast kinetics) and to
      compare it with 3D dynamic TR-CE-MRA using ASSET alone in the assessment of
      intracranial arteriovenous malformations (AVMs). MATERIALS AND METHODS: Twenty
      consecutive patients with angiographically confirmed AVMs were investigated using
      both 3D dynamic TR-CE-MRA techniques. Examinations were compared with respect to
      image quality, spatial resolution, number and type of feeders and drainers, nidus
      size, presence of early venous filling and temporal resolution. Digital
      subtraction angiography was used as standard of reference. RESULTS: The higher
      temporal and spatial resolution of 3D dynamic TR-CE-MRA TRICKS ASSET allowed a
      better assessment of intracranial vascular malformations, namely better depiction
      of feeders, drainers and better detection of early venous drainage. There was no
      significant difference between them in terms of nidus size. CONCLUSION: 3D
      dynamic TR-CE-MRA combining parallel imaging and a time-resolved method with
      subsecond and submillimeter resolution could become the first-line investigation
      technique in both diagnosis and follow-up of intracranial AVMs.

PMID- 19097094
TI  - Absolute blood contrast concentration and blood signal saturation on myocardial
      perfusion MRI: estimation from CT data.
AB  - PURPOSE: To determine the optimal contrast injection rate and absolute blood
      gadolinium concentration for optimal first-pass imaging. MATERIALS AND METHODS:
      The concentration of contrast medium in left ventricle (LV) was estimated from
      dynamic computed tomography (CT) by administering iodinated contrast medium of
      volume (0.2 mL/kg) equivalent to 0.1 mmol/kg of gadolinium injection in 50
      subjects. A blood sample study was performed to determine the relationship
      between blood signal and gadolinium concentration on perfusion MRI. RESULTS: The
      mean peak gadolinium concentration in LV increased as the injection rate
      increased from 1 mL/sec (3.7 +/- 1.2 mM), to 4 mL/sec (6.9 +/- 2.7 mM) (P <
      0.01). However, no significant improvement was found with an increase in the
      injection rate from 4 mL/sec to 5 mL/sec (6.8 +/- 1.5 mM, P = 0.86). In a blood
      sample study the linear relationship between blood signal and gadolinium
      concentration was maintained in the range of < or =0.67 mM (r = 0.992), which
      corresponds to a peak blood concentration following a 0.01 mmol/kg gadolinium
      injection. CONCLUSION: The optimal contrast injection rate for myocardial
      perfusion magnetic resonance imaging (MRI) appears to be 4 mL/sec. Saturation of
      arterial input signal is inevitable if the dose of gadolinium contrast medium
      exceeds 0.01 mmol/kg. These findings are essential for accurate quantification of
      myocardial blood flow from perfusion MRI.

PMID- 19097096
TI  - Restricted canonical correlation analysis in functional MRI-validation and a
      novel thresholding technique.
AB  - PURPOSE: To validate the performance of an analysis method for fMRI data based on
      restricted canonical correlation analysis (rCCA) and adaptive filtering, and to
      increase the usability of the method by introducing a new technique for
      significance estimation of rCCA maps. MATERIALS AND METHODS: Activation data from
      a language task and also a resting state fMRI data were collected from eight
      volunteers. Data was analyzed using both the rCCA method and the General Linear
      Model (GLM). A modified Receiver Operating Characteristic (ROC) method was used
      to evaluate the performance of the different analysis methods. The area under a
      fraction of the ROC curve was used as a measure of performance. On resting state
      data the fraction of voxels above certain significance thresholds were used to
      evaluate the significance estimation method. RESULTS: The rCCA method scored
      significantly higher on the area under the ROC curve than the GLM. The fraction
      of activated voxels determined by thresholding according to the introduced
      significance estimation technique showed good agreement with the thresholds
      selected. CONCLUSION: The rCCA method is an effective analysis tool for fMRI data
      and its usability is increased with the introduced significance estimation
      method.

PMID- 19097097
TI  - Computational and experimental optimization of a double-tuned (1)H/(31)P four
      ring birdcage head coil for MRS at 3T.
AB  - PURPOSE: To optimize the homogeneity and efficiency of the B(1) magnetic field of
      a four-ring birdcage head coil that is double-tuned at the Larmor frequencies of
      both (31)P and (1)H and optimized to acquire magnetic resonance spectroscopy
      (MRS) data at 3T for the study of infants. MATERIALS AND METHODS: We developed a
      finite difference time domain (FDTD) tool in-house to iteratively compute and
      seek the range of geometric and electromagnetic parameters of a dual-tuned, four
      ring birdcage coil that would produce the desired resonance patterns, optimize
      homogeneity of the B(1)-field, and maximize efficiency of the coil. To
      demonstrate the validity of our computational results, we constructed three RF
      coils: one dual-tuned coil that was based on the calculated optimized parameters
      and two single-tuned coils that had dimensions similar to those of the dual-tuned
      coil, but tuned at the Larmor frequencies of both (31)P and (1)H, respectively.
      We then tested and compared the performances of the dual-tuned coil and single
      tuned coils at both of these frequencies. RESULTS: We found that a dual-tuned,
      four-ring birdcage coil with a diameter of 180 mm, an inner birdcage length of
      100-300 mm, and an outer birdcage length of 25-100 mm produces the desired
      resonance patterns. For the use of this coil with human infants, optimization of
      the homogeneity of the B(1) field, combined with improved coil efficiency,
      yielded a dual-tuned birdcage coil with diameter of 180mm, an inner birdcage
      length of 150 mm, an outer birdcage length of 25 mm, and corresponding inner and
      outer capacitances of 17.2 pF and 7.6 pF, respectively. The experimental results
      from a constructed coil having the same parameters with the modeled coil agreed
      well with the computational results from the modeled coil. This optimized design
      overcame the deficiencies of existing dual-tuned, four-ring birdcage coils.
      CONCLUSION: The homogeneity and efficiency of the B(1) field for (31)P/(1)H dual
      tuned, four-ring birdcage coils can be optimized well using our FDTD tool,
      especially at high static magnetic fields (B(0)).

PMID- 19097098
TI  - Retrospective 3D registration of trabecular bone MR images for longitudinal
      studies.
AB  - PURPOSE: To evaluate an automatic 3D registration algorithm for serial high
      resolution images of trabecular bone (TB) in studies designed to evaluate the
      response of the trabecular architecture to intervention or disease progression.
      MATERIALS AND METHODS: An efficient algorithm for registering high-resolution 3D
      images of TB is presented. The procedure identifies the six parameters of rigid
      displacement between two scans performed at different timepoints. By assuming a
      relatively small through-plane rotation, considerable time is saved by combining
      the results of a collection of regional 2D registrations throughout the TB region
      of interest (ROI). The algorithm was applied to 26 pairs of MR images acquired 6
      months apart. Reproducibility of local TB structural parameters (plate, rod, and
      junction density) computed in manually selected regions were compared between
      baseline and registered follow-up images. RESULTS: All 26 registrations were
      completed successfully in less than 30 seconds per image pair. The resampled
      follow-up images agreed with baseline to around one pixel throughout the volume
      at 137 x 137 x 410 microm(3) image resolution. Structural parameters in each
      region correlated well from baseline to follow-up with intraclass correlation
      coefficients ranging between 85%-97% for TB plate density. Interregional
      variations in the parameters were large as compared with intraregion
      reproducibility. CONCLUSION: The proposed algorithm was successful in
      automatically registering baseline and follow-up TB images in a translational
      study, and may be useful in regional analyses in longitudinal MR studies of TB
      architecture.

PMID- 19097099
TI  - Imaging age-related cognitive decline: A comparison of diffusion tensor and
      magnetization transfer MRI.
AB  - PURPOSE: To determine which MR technique was the most sensitive to age-related
      white matter damage. We compared both diffusion tensor imaging (DTI) and
      magnetization transfer (MT) maps to determine which technique correlated most
      strongly with cognitive function in a middle-aged and elderly community
      population. MATERIALS AND METHODS: In all, 64 healthy subjects (aged 50-90)
      underwent MRI and neuropsychology. Histograms were generated for white matter
      mean diffusivity (MD), fractional anisotropy (FA), and MT ratio (MTR). White
      matter hyperintensity volume (WMH) and brain volume were also determined.
      Composite neuropsychological scores were derived for 4 cognitive domains
      (executive function, working memory, episodic memory, and information processing
      speed). RESULTS: All MRI parameters correlated with age (FA r = 0.726, P < 0.001;
      MD r = -0.619 P < 0.001, MTR r = -0.566, P < 0.001, WMH r = 0.511, P < 0.001).
      All MRI parameters correlated with cognition, but DTI, and particularly FA,
      correlated most strongly. Adding DTI parameters explained more variance in
      cognition than WMH alone; the increase was greatest with FA, which alone
      explained 45%, 33%, and 25% of the variance in cognition for information
      processing speed, episodic memory, and executive function, respectively.
      CONCLUSION: DTI appears the most sensitive imaging parameter to determine age
      related white matter damage. The stronger relationship with FA suggests that
      axonal damage is important in age-related cognitive decline.

PMID- 19097100
TI  - Stimulation threshold comparison of time-varying magnetic pulses with different
      waveforms.
AB  - PURPOSE: To clarify whether sinusoidal pulses possess lower thresholds than
      rectangular ones at perception threshold, a statement often made that contradicts
      the theory of stimulation. MATERIALS AND METHODS: The results of a nerve
      stimulation study with 65 volunteers and with trapezoidal and sinusoidal gradient
      pulses were used to apply the combination of the electric field, induced in the
      tissue of the human body, with the "Fundamental Law of Electrostimulation." This
      law claims that the waveshape of a pulse is not essential as long as the
      amplitude of the pulse does not decrease below rheobase (rheobase condition).
      RESULTS: If the rheobase condition is applied to sinusoidal waveforms and the
      pulse duration and amplitude is corrected accordingly, both trapezoidal and
      sinusoidal gradient pulses have identical threshold amplitudes as a function of
      pulse duration. CONCLUSION: The "Fundamental Law of Electrostimulation,"
      including the "rheobase condition," proved to be a good basis for describing
      magnetic field stimulation (magnetostimulation) and that application of it to
      magnetostimulation is suitable as the basis for describing magnetic field
      stimulation with various waveforms. For nonrectangular pulses, pulse durations
      and pulse amplitudes must be corrected according to the "rheobase condition." The
      exponential Blair Equation is less suited to be applied in magnetostimulation.

PMID- 19097101
TI  - Optimum fuzzy filters for phase-contrast magnetic resonance imaging segmentation.
AB  - PURPOSE: To develop and validate a multidimensional segmentation and filtering
      methodology for accurate blood flow velocity field reconstruction from phase
      contrast magnetic resonance imaging (PC MRI). MATERIALS AND METHODS: The proposed
      technique consists of two steps: (1) the boundary of the vessel is automatically
      segmented using the active contour approach; and (2) the noise embedded within
      the segmented vector field is selectively removed using a novel fuzzy adaptive
      vector median filtering (FAVMF) technique. This two-step segmentation process was
      tested and validated on 111 synthetically generated PC MRI slices and on 10
      patients with congenital heart disease. RESULTS: The active contour technique was
      effective for segmenting blood vessels having a sensitivity and specificity of
      93.1% and 92.1% using manual segmentation as a reference standard. FAVMF was the
      superior technique in filtering out noise vectors, when compared with other
      commonly used filters in PC MRI (P < 0.05). The peak wall shear rate calculated
      from the PC MRI data (248 +/- 39 sec(-1)), was significantly decreased to (146 +/
      26 sec(-1)) after the filtering process. CONCLUSION: The proposed two-step
      segmentation and filtering methodology is more accurate compared to a single-step
      segmentation process for post-processing of PC MRI data.

PMID- 19097102
TI  - Diffusion measurements and diffusion tensor imaging with noisy magnitude data.
AB  - PURPOSE: To compare an unbiased method for estimation of the diffusion
      coefficient to the quick, but biased, log-linear (LL) method in the presence of
      noisy magnitude data. MATERIALS AND METHODS: The magnitude operation changes the
      signal distribution in magnetic resonance (MR) images from Gaussian to Rician. If
      not properly taken into account, this will introduce a bias in the estimated
      diffusion coefficient. We compare two methods by means of Monte Carlo
      simulations. The first one applies least-squares fitting of the measured signal
      to the median (MD) value of the probability density function. The second method
      is uncorrected LL estimation. We also perform a high-resolution diffusion tensor
      experiment. RESULTS: The uncorrected LL estimator is heavily biased at low signal
      to-noise ratios. The bias has a significant effect on image quality. The MD
      estimator is accurate and produces images with excellent contrast. CONCLUSION: In
      the presence of noisy magnitude data, unbiased estimation is essential in
      diffusion measurements and diffusion tensor imaging.

PMID- 19097103
TI  - Magnetic resonance imaging enhanced by superparamagnetic iron oxide particles:
      usefulness for distinguishing between focused ultrasound-induced blood-brain
      barrier disruption and brain hemorrhage.
AB  - PURPOSE: To investigate the usefulness of a fully flow-compensated heavy T2*
      weighted imaging enhanced by superparamagnetic iron oxide (SPIO) particles for
      distinguishing between focused ultrasound-induced disruption of blood-brain
      barrier (BBB) and brain hemorrhage. MATERIALS AND METHODS: Focused ultrasound
      (frequency: 1.5 MHz) was used to induce disruption of the BBB in 39 rats. Two T2*
      weighted images were obtained before and after SPIO administration. Preenhanced
      T2*-weighted images were used to detect hemorrhage. Detection of BBB disruption
      was performed on SPIO-enhanced images. Thirty-four rats were sacrificed after
      magnetic resonance (MR) scanning for histological confirmation of brain lesions.
      The remaining five animals were followed up for 35 days. Prussian blue staining
      was performed on histological sections to detect SPIO particles in the brain.
      RESULTS: After SPIO injection the areas of BBB disruption in rat brain were
      significantly enlarged. The area of mismatch between the T2*-weighted images
      indicated a safe region where BBB opening occurred without hemorrhagic
      complications. In the longitudinal study, removal of SPIO occurred at a faster
      rate in hemorrhagic areas, albeit being closer to that occurring in the liver.
      The presence of SPIO was confirmed by Prussian blue staining in brain parenchyma
      and capillary endothelial cells in areas of BBB disruption. CONCLUSION: T2*
      weighted images-either with and without SPIO enhancement-may differentiate
      focused ultrasound-induced BBB disruption from brain hemorrhage.

PMID- 19097104
TI  - Cerebral blood flow estimation in vivo using local tissue reference functions.
AB  - PURPOSE: To evaluate the use of bolus signals obtained from tissue as reference
      functions (or local reference functions [LRFs]) rather than arterial input
      functions (AIFs) when deriving cross-calibrated cerebral blood flow (CBF(CC))
      estimates via deconvolution. MATERIALS AND METHODS: AIF and white matter (WM) LRF
      CBF(CC) maps (cross-calibrated so that normal WM was 23.7 mL/minute/100 g)
      derived using singular value decomposition (SVD) were examined in 28 ischemic
      stroke patients. Median CBF(CC) estimates from normal gray matter (GM) and
      ischemic tissue were obtained. RESULTS: AIF and LRF median CBF(CC) estimates
      resembled one another for all 28 patients (average paired CBF(CC) difference 0.4
      +/- 1.7 mL/minute/100 g and -0.4 +/- 1.4 mL/minute/100 g in GM and ischemic
      tissue, respectively). Wilcoxon signed-rank comparisons of patient median CBF(CC)
      measurements revealed no statistically significant differences between using AIFs
      and LRFs (P > 0.05). CONCLUSION: If CBF is quantified using a patient-specific
      cross-calibration factor, then LRF CBF estimates are at least as accurate as
      those from AIFs. Therefore, until AIF quantification is achievable in vivo,
      perfusion protocols tailored for LRFs would simplify the methodology and provide
      more reliable perfusion information.

PMID- 19097105
TI  - Strain-encoded (SENC) magnetic resonance imaging to evaluate regional
      heterogeneity of myocardial strain in healthy volunteers: Comparison with
      conventional tagging.
AB  - PURPOSE: To evaluate the ability of strain-encoded (SENC) magnetic resonance
      imaging (MRI) for regional systolic and diastolic strain analysis of the
      myocardium in healthy volunteers. MATERIALS AND METHODS: Circumferential and
      longitudinal peak systolic strain values of 75 healthy volunteers (35 women and
      40 men, mean age 44 +/- 12 years) were measured using SENC at 1.5T. MR tagging
      was used as the reference standard for measuring regional function. Diastolic
      function was assessed in the 10 youngest (24 +/- 8 years) and 10 oldest (62 +/- 5
      years) subjects. RESULTS: Peak strain values assessed with SENC were comparable
      to those obtained by MR tagging, showing narrow limits of agreement (limits of
      agreement -5.6% to 8.1%). Regional heterogeneity was observed between different
      segments of the left ventricle (LV) by both techniques (P < 0.001). Longitudinal
      strain obtained by SENC was also heterogenous (P < 0.001). Interestingly, no age-
      or gender-specific differences in peak systolic strain were observed, whereas the
      peak rate of relaxation of circumferential strain rate was decreased in the older
      group. CONCLUSION: SENC is a reliable tool for accurate and objective
      quantification of regional myocardial systolic as well as diastolic function. In
      agreement with tagged MRI, SENC detected slightly heterogeneous myocardial strain
      within LV segments.

PMID- 19097107
TI  - Calibrated magnetic resonance hydrometry to quantify pancreatic juice: a
      preliminary study.
AB  - PURPOSE: To investigate the effectiveness of the calibrated MR hydrometry (CMRH)
      method for accurately measuring pancreatic secretion. MATERIALS AND METHODS: All
      studies were performed on a 1.5-T MR system using a fat-suppressed, single-shot
      half-Fourier fast spin-echo sequence with a standard body coil. A certain volume
      (20 mL) of saline solution was employed as an extrabody calibrator. The validity
      of the CMRH method was tested both in vitro and in vivo, and actual and
      calculated volumes were compared. RESULTS: The in vitro study yielded a high
      correlation (r = 0.99; P < 0.0001) between the actual volume of saline solution
      in the imaging field and the calculated volume. In the in vivo study, for all
      volunteers, there was a very strong and significant positive correlation between
      the measured signal intensities or calculated volumes and actual volumes
      (correlation coefficient range: 0.94-0.99; P < 0.0001). CONCLUSION: This
      preliminary study shows that CMRH is an effective tool to measure the amount of
      pancreatic fluid secretion.

PMID- 19097106
TI  - Contrast agent dose effects in cerebral dynamic susceptibility contrast magnetic
      resonance perfusion imaging.
AB  - PURPOSE: To study the contrast agent dose sensitivity of hemodynamic parameters
      derived from brain dynamic susceptibility contrast MRI (DSC-MRI). MATERIALS AND
      METHODS: Sequential DSC-MRI (1.5T gradient-echo echo-planar imaging using an echo
      time of 61-64 msec) was performed using contrast agent doses of 0.1 and 0.2
      mmol/kg delivered at a fixed rate of 5.0 mL/second in 12 normal subjects and 12
      stroke patients. RESULTS: 1) Arterial signal showed the expected doubling in
      relaxation response (DeltaR2*) to dose doubling. 2) The brain signal showed a
      less than doubled DeltaR2* response to dose doubling. 3) The 0.2 mmol/kg dose
      studies subtly underestimated cerebral blood volume (CBV) and cerebral blood flow
      (CBF) relative to the 0.1 mmol/kg studies. 4) In the range of low CBV and CBF,
      the 0.2 mmol/kg studies overestimated the CBV and CBF compared with the 0.1
      mmol/kg studies. 5) The 0.1 mmol/kg studies reported larger ischemic volumes in
      stroke. CONCLUSION: Subtle but statistically significant dose sensitivities were
      found. Therefore, it is advisable to carefully control the contrast agent dose
      when DSC-MRI is used in clinical trials. The study also suggests that a 0.1
      mmol/kg dose is adequate for hemodynamic measurements.

PMID- 19097108
TI  - Diagnostic utility of diffusion-weighted MR imaging and apparent diffusion
      coefficient value for the diagnosis of adrenal tumors.
AB  - PURPOSE: To determine the utility of diffusion-weighted MR imaging (DWI) for the
      diagnosis of adrenal tumors. MATERIALS AND METHODS: Forty-two patients (24 men
      and 18 women; age, 61.5 +/- 12.7 years old; range, 34-86 years) with 43 adrenal
      tumors (11 functioning cortical adenomas, 20 nonfunctioning cortical adenomas, 7
      metastatic tumors, and 5 pheochromocytomas) were retrospectively investigated.
      DWIs were obtained by single-shot spin-echo type echo-planar imaging sequence
      (1.5 Tesla [T]; TR = 8000 ms, TE = 72, b-factor = 0 and 1000 s/mm(2)), and
      apparent diffusion coefficient (ADC) value was calculated. Chemical shift images
      were obtained by gradient echo sequence (TR = 161, TE = 2.38 [out-of-phase, OP]
      and 4.76 [in-phase, IP], FA = 60), and the signal intensity index (SII; [IP
      OP]/IP *100%) was calculated. RESULTS: There was no difference in ADC values
      between adenomas (1.09 +/- 0.29*10(-3) mm(2)/s; range, 0.52-1.64) and metastatic
      tumors (0.85 +/- 0.26*10(-3); 0.51-1.23; p = 0.14). Pheochromocytomas showed the
      higher mean ADC value (1.59 +/- 0.34*10(-3); 1.04-1.96) compared with those of
      adenomas or metastatic tumors (P < 0.05 and P < 0.005, respectively). The mean
      SII of adenomas (62.1 +/- 17.9%; 14.5-88.4) was significantly higher than those
      of pheochromocytomas (4.0 +/- 10.0%; -19.6-3.3; P < 0.005) or metastatic tumors (
      1.5 +/- 11.7%; -18.3-8.2; P < 0.01). There was no correlation between ADC values
      and SII. CONCLUSION: Although pheochromocytomas showed higher ADC values, we did
      not find that ADC value had diagnostic utility for differentiating adenomas and
      metastatic tumors.

PMID- 19097109
TI  - Phosphorus-31 magnetic resonance spectroscopy of skeletal muscle in maternally
      inherited diabetes and deafness A3243G mitochondrial mutation carriers.
AB  - PURPOSE: To investigate high-energy phosphate metabolism in striated skeletal
      muscle of patients with Maternally Inherited Diabetes and Deafness (MIDD)
      syndrome. MATERIALS AND METHODS: In 11 patients with the MIDD mutation (six with
      diabetes mellitus [DM] and five non-DM) and eight healthy subjects,
      phosphocreatine (PCr) and inorganic phosphate (Pi) in the vastus medialis muscle
      was measured immediately after exercise using (31)P-magnetic resonance
      spectroscopy (MRS). The half-time of recovery (t1/2) of monoexponentially fitted
      (PCr+Pi)/PCr was calculated from spectra obtained every 4 seconds after cessation
      of exercise. A multiple linear regression model was used for statistical
      analysis. RESULTS: Patients with the MIDD mutation showed a significantly
      prolonged t1/2 (PCr+Pi)/PCr after exercise as compared to controls (13.6+/-3.0
      vs. 8.7+/-1.3 sec, P = 0.01). No association between the presence of DM and t1/2
      (PCr + Pi)/PCr was found (P = 0.382). CONCLUSION: MIDD patients showed impaired
      mitochondrial oxidative phosphorylation in skeletal muscle shortly after
      exercise, irrespective of the presence of DM.

PMID- 19097110
TI  - Higher-order contrast functions improve performance of independent component
      analysis of fMRI data.
AB  - PURPOSE: To evaluate the performance of different contrast functions used in
      Independent Component Analysis (ICA) of functional magnetic resonance imaging
      (fMRI) data at low signal-to-noise ratio (SNR), present in fMRI paradigms such as
      resting-state acquisitions. MATERIALS AND METHODS: Metrics were defined to
      estimate both the accuracy and robustness of contrast functions under varying
      source distributions. Simulations were performed to compare the performance of
      lower-order (such as ln cosh) to higher-order (such as kurtosis) contrast
      functions using Laplacian source distributions corrupted with Gaussian noise. The
      ln cosh and kurtosis contrast functions were also compared using resting-state
      fMRI data from 10 normal adult volunteers. RESULTS: Higher-order contrast
      functions provided superior performance compared to lower-order contrast
      functions in the evaluation of metrics and via the simulations in the presence of
      a significant amount of noise. The performance of kurtosis was not statistically
      significantly different from that of a theoretically optimized contrast function.
      The choice of contrast function was found to result in substantial (R < 0.9)
      differences in 40% of the components found from the resting-state fMRI data.
      CONCLUSION: The use of higher-order contrast functions, such as kurtosis, may
      provide superior performance in ICA analysis of fMRI data with low SNR.

PMID- 19097111
TI  - Improved bolus arrival time and arterial input function estimation for tracer
      kinetic analysis in DCE-MRI.
AB  - PURPOSE: To develop a methodology for improved estimation of bolus arrival time
      (BAT) and arterial input function (AIF) which are prerequisites for tracer
      kinetic analysis of dynamic contrast-enhanced magnetic resonance imaging (DCE
      MRI) data and to verify the applicability of the same in the case of intracranial
      lesions (brain tumor and tuberculoma). MATERIALS AND METHODS: A continuous
      piecewise linear (PL) model (with BAT as one of the free parameters) is proposed
      for concentration time curve C(t) in T(1)-weighted DCE-MRI. The resulting
      improved procedure suggested for automatic extraction of AIF is compared with
      earlier methods. The accuracy of BAT and other estimated parameters is tested
      over simulated as well as experimental data. RESULTS: The proposed PL model
      provides a good approximation of C(t) trends of interest and fit parameters show
      their significance in a better understanding and classification of different
      tissues. BAT was correctly estimated. The automatic and robust estimation of AIF
      obtained using the proposed methodology also corrects for partial volume effects.
      The accuracy of tracer kinetic analysis is improved and the proposed methodology
      also reduces the time complexity of the computations. CONCLUSION: The PL model
      parameters along with AIF measured by the proposed procedure can be used for an
      improved tracer kinetic analysis of DCE-MRI data.

PMID- 19097112
TI  - Advances of 3T MR imaging in visualizing trabecular bone structure of the
      calcaneus are partially SNR-independent: analysis using simulated noise in
      relation to micro-CT, 1.5T MRI, and biomechanical strength.
AB  - PURPOSE: To investigate differences in magnetic resonance imaging (MRI) of
      trabecular bone at 1.5T and 3.0T and to specifically study noise effects on the
      visualization and quantification of trabecular architecture using conventional
      histomorphometric and nonlinear measures of bone structure. MATERIALS AND
      METHODS: Sagittal MR images of 43 calcaneus specimens (donor age: 81 +/- 10
      years) were acquired at 1.5T and 3.0T using gradient echo sequences. Noise was
      added to obtain six sets of images with decreasing signal-to-noise ratios (SNRs).
      Micro-CT images were obtained from biopsies taken from 37 calcaneus samples and
      bone strength was determined. Morphometric and nonlinear structure parameters
      were calculated in all datasets. RESULTS: Originally, SNR was 1.5 times higher at
      3.0T. In the simulated image sets, SNR was similar at both fields. Trabecular
      dimensions measured by microCT were adequately estimated by MRI, with residual
      errors (e(r)), ranging from 16% to 2.7% at 3.0T. Comparing e(r) at similar SNR,
      3.0T consistently displayed lower errors than 1.5T (eg, bone fraction at SNR
      approximately 4: e(r)[3.0T] = 15%; e(r)[1.5T] = 21%, P < 0.05). CONCLUSION: The
      advances of 3.0T compared to 1.5T in visualizing trabecular bone structure are
      partially SNR-independent. The better performance at 3.0T may be explained by
      pronounced susceptibility, enhancing the visualization of thin trabecular
      structures.

PMID- 19097113
TI  - Visualization of the lenticulostriate artery with flow-sensitive black-blood
      acquisition in comparison with time-of-flight MR angiography.
AB  - PURPOSE: To evaluate the capability of flow-sensitive black blood (FSBB)
      acquisition to visualize the lenticulostriate artery (LSA) in comparison with
      time-of-flight (TOF) angiography. MATERIALS AND METHODS: Twenty-one healthy
      subjects (13 males and 8 females, 19-44 years old) were enrolled in this study
      after obtaining written informed consent. Magnetic resonance imaging (MRI)
      examinations were performed with FSBB and TOF to visualize the LSA using a 1.5T
      MRI unit. In FSBB acquisition a motion probing gradient of b = 4 sec/mm(2) was
      applied to dephase blood flow. Images were reconstructed into coronal sections
      and were evaluated in terms of number, length, and image quality at origins and
      distal areas of visualized LSA branches with a four-point scale. RESULTS: In all,
      145 LSA branches were visualized with FSBB and 66 branches with TOF. There was no
      LSA visualized only with TOF. In all evaluated terms, FSBB was significantly
      better than TOF. CONCLUSION: We could better visualize the LSA with FSBB than
      with TOF, both quantitatively and qualitatively. FSBB is a promising method,
      although it remains to be evaluated in clinical cases.

PMID- 19097114
TI  - Increased SNR and reduced distortions by averaging multiple gradient echo signals
      in 3D FLASH imaging of the human brain at 3T.
AB  - PURPOSE: To demonstrate how averaging of multiple gradient echoes can improve
      high-resolution FLASH (fast low angle shot) magnetic resonance imaging (MRI) of
      the human brain. MATERIALS AND METHODS: 3D-FLASH with multiple bipolar echoes was
      studied by simulation and in three experiments on human brain at 3T. First, the
      repetition time (TR) was increased by the square of the flip angle to maintain
      contrast as derived by theory. Then the number of echoes was increased at
      constant TR with bandwidths between 110 and 1370 Hz/pixel. Finally, signals of a
      12-echo acquisition train (echo times 4.9-59 msec) were averaged consecutively to
      study the increase in SNR. RESULTS: At unchanged contrast, the signal increased
      proportionally with flip angle and sqrt(TR). Increasing the bandwidth improved
      delineation of the basal cortex and vessels, while most of the loss in the signal
      to-noise ratio (SNR) was recovered by averaging. Consecutive averaging increased
      the SNR to reach maximum efficiency at an echo train length corresponding roughly
      to T(2) (*). CONCLUSION: SNR is gained efficiently by acquiring additional echoes
      and increasing TR (and flip angle accordingly to maintain contrast) until the
      associated T(2) (*) loss in the averaged signal consumes the sqrt(TR) increase in
      the steady state. A bandwidth of 350 Hz/pixel or higher and echo trains shorter
      than T(2) (*) are recommended.

PMID- 19097115
TI  - Clinical evaluation of automated scan prescription of knee MR images.
AB  - PURPOSE: To compare an automated scan planning method to manual scan positioning
      in routine knee magnetic resonance imaging (MRI) studies. MATERIALS AND METHODS:
      The automated scan planning method uses anatomical landmarks in a 3D survey of
      the knee. The method is trained by example plannings, consisting of manual slice
      positioning by an experienced technologist in 15 MRI studies. Automated knee MR
      examinations obtained in three geometries in 50 consecutive patients were
      compared to those obtained in 50 consecutive control patients, where imaging
      planes were planned manually. Anatomical coverage and slice angulation were
      scored for each geometry on a 4-grade scale by an experienced radiologist blinded
      to the way of planning; groups were compared using a Mann-Whitney U-test.
      RESULTS: In 150 automated sequences the technologist adapted slice positioning in
      four cases (addition of slices to adapt to the size of the knee), representing
      the only automated sequences that received a poor rating. Thirteen sequences with
      manual planning received a poor rating. No difference in quality was found (P >
      0.05) between automated and manual plannings for coronal coverage, sagittal
      coverage and angulation, and transverse angulation. Rating of automated planning
      was higher for transverse coverage, but lower than manual planning for coronal
      angulation. CONCLUSION: Automated sequence prescription for knee MRI is feasible
      in clinical practice, with similar quality as manual positioning.

PMID- 19097116
TI  - Caudate nuclei volume, diffusion tensor metrics, and T(2) relaxation in healthy
      adults and relapsing-remitting multiple sclerosis patients: implications for
      understanding gray matter degeneration.
AB  - PURPOSE: To investigate the utility of caudate nuclei (CN) macro- and
      microstructural metrics as markers of gray matter degeneration in healthy adults
      and relapsing-remitting multiple sclerosis (RRMS) patients. MATERIALS AND
      METHODS: The normal age- and pathology-related changes in caudate nuclei volume
      (CNV), the corresponding diffusion tensor metrics, and the T(2) relaxation times
      were measured in a cohort of 32 healthy adults (12 men/20 women; age range 21-59
      years) and 32 age-matched RRMS patients (8 men/34 women; age range 21-57 years).
      RESULTS: Smaller values in both the absolute CNV and the caudate volume ratio
      relative to the total intracranial volume (CNVp) were observed in the RRMS group
      relative to healthy controls. The fractional anisotropy (FA), based on the
      diffusion tensor imaging (DTI) of the CN increased with age in healthy adults (r
      = 0.52; P = 0.003) but not in patients (r = 0.28; P = 0.12). The caudate FA value
      was approximately 9% larger in RRMS patients relative to controls (P = 0.001).
      The mean diffusivity of the CN was greater in the RRMS group compared to controls
      (P = 0.02). The caudate T(2) relaxation times were smaller in the RRMS group
      relative to the control group (3% reduction, P = 0.05). T(2) relaxation times did
      not exhibit age-related changes (P > 0.35) in either cohort. Strong and
      significant correlations between CNVp and whole-brain lesion load (r = -0.48; P =
      0.005) and whole-brain CSF fraction (r = -0.46; P = 0.01) were also noted.
      CONCLUSION: These preliminary findings indicate that caudate DTI-derived metrics
      can serve as potential quantitative radiological markers of MS pathology.

PMID- 19097117
TI  - Fibroblast growth factor 9 signaling inhibits airway smooth muscle
      differentiation in mouse lung.
AB  - In mammalian lungs, airway smooth muscle cells (airway SMCs) are present in the
      proximal lung adjacent to bronchi and bronchioles, but are absent in the distal
      lung adjacent to terminal sacs that expand during gas exchange. Evidence suggests
      that this distribution is essential for the formation of a functional respiratory
      tree, but the underlying genetic mechanism has not been elucidated. In this
      study, we test the hypothesis that fibroblast growth factor 9 (Fgf9) signaling is
      essential to restrict SMC differentiation to the proximal lung. We show that loss
      of Fgf9 or conditional inactivation of Fgf receptors (Fgfr) 1 and 2 in mouse lung
      mesenchyme results in ectopic SMCs. Our data support a model where FGF9 maintains
      a SMC progenitor population by suppressing differentiation and promoting growth.
      This model also represents our findings on the genetic relationship between FGF9
      and sonic hedgehog (SHH) in the establishment of airway SMC pattern.

PMID- 19097119
TI  - Natural variation in embryo mechanics: gastrulation in Xenopus laevis is highly
      robust to variation in tissue stiffness.
AB  - How sensitive is morphogenesis to the mechanical properties of embryos? To
      estimate an upper bound on the sensitivity of early morphogenetic movements to
      tissue mechanical properties, we assessed natural variability in the apparent
      stiffness among gastrula-stage Xenopus laevis embryos. We adapted micro
      aspiration methods to make repeated, nondestructive measurements of apparent
      tissue stiffness in whole embryos. Stiffness varied by close to a factor of 2
      among embryos within a single clutch. Variation between clutches was of similar
      magnitude. On the other hand, the direction of change in stiffness over the
      course of gastrulation was the same in all embryos and in all clutches. Neither
      pH nor salinity--two environmental factors we predicted could affect variability
      in nature--affected tissue stiffness. Our results indicate that gastrulation in
      X. laevis is robust to at least twofold variation in tissue stiffness.

PMID- 19097120
TI  - The importance of attitudinally appropriate description of cardiac anatomy.
AB  - The essence of anatomic description is to account for structures as they lie
      within the body as viewed in the so-called anatomic position. This important
      basic principle of gross anatomy has been ignored for years by those describing
      the relationships of structures within the heart, these cardiac components
      usually being described in the setting of the heart removed from the body, and
      positioned on its apex. With the increasing use in clinical practice of
      tomographic techniques for diagnosis, in which the heart is viewed as it lies
      within the body, this conventional approach to description of cardiac structures
      becomes increasingly confusing. Thus, when the heart is viewed in attitudinally
      appropriate fashion, with the apex pointing to the left, and with the so-called
      right heart chambers positioned anteriorly relative to the so-called left
      counterparts, the current adjectives used for description are found to be
      wanting. For example, with the heart in the position it occupies during life, the
      so-called posterior descending coronary artery is seen to be positioned
      inferiorly relative to the ventricular mass. It is more correct to describe this
      artery as being inferior and interventricular. Such a change has major clinical
      significance, since blockage of the artery produces inferior myocardial
      infarction, the leads used for electrocardiographic recording being placed so as
      to respect the anatomic position. Another example of the deficiencies of the
      "Valentine" approach to cardiac description is seen when the mitral valve is
      viewed in attitudinally appropriate fashion. The papillary muscles supporting the
      tendinous cords are seen to be located inferiorly and adjacent to the ventricular
      septum, and superiorly and located on the posterior left ventricular wall when
      viewed in this fashion. Currently, however, the inferoseptal muscle is described
      as being posteromedial. Those performing electrophysiological studies of the
      heart have already appreciated the problems created by assessing the heart in
      "Valentine" fashion, since when described in this way, a catheter passing upwards
      through the inferior caval vein is said to progress in an anterior fashion. A
      committee has recommended use of attitudinally appropriate terminology to avoid
      these problems. We suggest that those teaching cardiac anatomy in medical schools
      should also insist on the use of attitudinally appropriate nomenclature when
      describing the heart, as is currently the case for all other structures in the
      body.

PMID- 19097121
TI  - Microfilament and microtubule assembly is required for the propagation of
      inositol trisphosphate receptor-induced Ca2+ waves in bovine aortic endothelial
      cells.
AB  - Ca2+ is a highly versatile second messenger that plays a key role in the
      regulation of numerous cell processes. One-way cells ensure the specificity and
      reliability of Ca2+ signals is by organizing them spatially in the form of waves
      that propagate throughout the cell or within a specific subcellular region. In
      non-excitable cells, the inositol 1,4,5-trisphosphate receptor (IP3R) is
      responsible for the release of Ca2+ from the endoplasmic reticulum. The spatial
      aspect of the Ca2+ signal depends on the organization of various elements of the
      Ca2+ signaling toolkit and varies from tissue to tissue. Ca2+ is implicated in
      many of endothelium functions that thus depend on the versatility of Ca2+
      signaling. In the present study, we showed that the disruption of caveolae
      microdomains in bovine aortic endothelial cells (BAEC) with methyl-beta
      cyclodextrin was not sufficient to disorganize the propagation of Ca2+ waves when
      the cells were stimulated with ATP or bradykinin. However, disorganizing
      microfilaments with latrunculin B and microtubules with colchicine both prevented
      the formation of Ca2+ waves. These results suggest that the organization of the
      Ca2+ waves mediated by IP3R channels does not depend on the integrity of caveolae
      in BAEC, but that microtubule and microfilament cytoskeleton assembly is crucial.

PMID- 19097122
TI  - Transcription factor TFII-I causes transcriptional upregulation of GRP78
      synthesis in prostate cancer cells.
AB  - Receptor-recognized forms of alpha(2)-macroglobulin (alpha(2)M*) bind to cell
      surface-associated GRP78 and induce proliferative and survival signaling in
      prostate cancer cells. As part of the cellular response to alpha(2)M*, GRP78
      expression is itself upregulated. In response to other stimuli, the transcription
      factor TFII-I upregulates GRP78 by binding to its gene promoter. We have,
      therefore, studied the role of TFII-I in transcriptional upregulation of GRP78 in
      1-LN human prostate cancer cells stimulated with alpha(2)M*. This treatment
      caused a two- to threefold increase in TFII-I and GRP78 synthesis from [(35)S]
      labeled precursor amino acids. Synthesis of both TFII-I and GRP78 were
      significantly reduced by silencing TFII-I gene expression or pretreatment of
      cells with genistein or actinomycin D. Confocal microscopy was employed to
      demonstrate relocation of TFII-I to the nucleus. In alpha(2)M*-stimulated cells,
      moreover, TFII-I bound to the GRP78 promoter as determined by CHIP assay. We also
      demonstrate binding of TFII-I to the c-fos promoter, consistent with its role in
      upregulating c-fos gene expression. In non-lymphoid cells, phosphorylated c-Src
      is an activator of TFII-I. Ligation of GRP78 on 1-LN cells with alpha(2)M* was
      followed by tyrosine phosphorylation of c-Src as well as TFII-I. We conclude that
      alpha(2)M*-induced increase in GRP78 synthesis is caused by transcriptional
      upregulation of TFII-I which binds to the GRP78 promoter and thus potentiates its
      cell survival and antipoptotic functions in 1-LN prostate cancer cells.

PMID- 19097123
TI  - Strain-specific viral properties of variant Creutzfeldt-Jakob disease (vCJD) are
      encoded by the agent and not by host prion protein.
AB  - Human CJD, endemic sheep scrapie, epidemic bovine spongiform encephalopathy
      (BSE), and other transmissible spongiform encephalopathies (TSEs), are caused by
      a group of related but molecularly uncharacterized infectious agents. The UK-BSE
      agent infected many species, including humans where it causes variant CJD (vCJD).
      As in most viral infections, different TSE disease phenotypes are determined by
      both the agent strain and the host species. TSE strains are most reliably
      classified by incubation time and regional neuropathology in mice expressing wild
      type (wt) prion protein (PrP). We compared vCJD to other human and animal derived
      TSE strains in both mice and neuronal cultures expressing wt murine PrP. Primary
      and serial passages of the human vCJD agent, as well as the highly selected
      mutant 263K sheep scrapie agent, revealed profound strain-specific
      characteristics were encoded by the agent, not by host PrP. Prion theory posits
      that PrP converts itself into the infectious agent, and thus short incubations
      require identical PrP sequences in the donor and recipient host. However, wt PrP
      mice injected with human vCJD brain homogenates showed dramatically shorter
      primary incubation times than mice expressing only human PrP, a finding not in
      accord with a PrP species barrier. All mouse passage brains showed the vCJD agent
      derived from a stable BSE strain. Additionally, both vCJD brain and monotypic
      neuronal cultures produced a diagnostic 19 kDa PrP fragment previously observed
      only in BSE and vCJD primate brains. Monotypic cultures can be used to identify
      the intrinsic, strain-determining molecules of TSE infectious particles.

PMID- 19097124
TI  - Microporous polyisocyanurate and its application in heterogeneous catalysis.

PMID- 19097125
TI  - Novel zinc porphyrin sensitizers for dye-sensitized solar cells: synthesis and
      spectral, electrochemical, and photovoltaic properties.
AB  - Novel meso- or beta-derivatized porphyrins with a carboxyl group have been
      designed and synthesized for use as sensitizers in dye-sensitized solar cells
      (DSSCs). The position and nature of a bridge connecting the porphyrin ring and
      carboxylic acid group show significant influences on the spectral,
      electrochemical, and photovoltaic properties of these sensitizers. Absorption
      spectra of porphyrins with a phenylethynyl bridge show that both Soret and Q
      bands are red-shifted with respect to those of porphyrin 6. This phenomenon is
      more pronounced for porphyrins 3 and 4, which have a pi-conjugated electron
      donating group at the meso position opposite the anchoring group. Upon
      introduction of an ethynylene group at the meso position, the potential at the
      first oxidation alters only slightly whereas that for the first reduction is
      significantly shifted to the positive, thus indicating a decreased HOMO-LUMO gap.
      Quantum-chemical (DFT) results support the spectroelectrochemical data for a
      delocalization of charge between the porphyrin ring and the amino group in the
      first oxidative state of diarylamino-substituted porphyrin 5, which exhibits the
      best photovoltaic performance among all the porphyrins under investigation. From
      a comparison of the cell performance based on the same TiO(2) films, the devices
      made of porphyrin 5 coadsorbed with chenodeoxycholic acid (CDCA) on TiO(2) in
      ratios [5]/[CDCA] = 1:1 and 1:2 have efficiencies of power conversion similar to
      that of an N3-based DSSC, which makes this green dye a promising candidate for
      colorful DSSC applications.

PMID- 19097127
TI  - Diastereoselective and enantioselective synthesis of tertiary alpha-hydroxy
      phosphonates through hydrogen-bond catalysis.

PMID- 19097126
TI  - Ammosamides A and B target myosin.

PMID- 19097128
TI  - Development and validation of a pharmacophore-based QSAR model for the prediction
      of CNS activity.
AB  - A QSAR model aimed at predicting central nervous system (CNS) activity was
      developed based on the structure-activity relationships of compounds from an in
      house database of "drug-like" molecules. These compounds were initially
      identified as "CNS-active" or "CNS-inactive", and pharmacophore 3D descriptors
      were calculated from multiple conformations for each structure. A linear
      discriminant analysis (LDA) was performed on this structure-activity matrix, and
      this QSAR model was able to correctly classify approximately 80 % in both a
      learning set and a validation set. For validation purposes, the LDA model was
      applied to compounds for which the blood-brain barrier (BBB) penetration was
      known, and all of them were correctly predicted. The model was also applied to
      960 other in-house compounds for which in vitro binding tests were performed on
      20 receptors known to be present at the CNS level, and a high correlation was
      observed between compounds predicted as CNS-active and experimental hits.
      Finally, the model was also applied to a set of 700 structures with known CNS
      activity or inactivity randomly chosen from public sources, and more than 70 % of
      the compounds were correctly classified, including novel CNS chemotypes. These
      results demonstrate the applicability of the model to novel chemical structures
      and its usefulness for designing original CNS-focused compound libraries.

PMID- 19097129
TI  - Synthesis of alginate oligosaccharides containing L-guluronic acids.
AB  - Making ends meet: The L-gulopyranosyl trichloroacetimidate and 1,6-anhydro-2,3-di
      O-benzyl-beta-L-gulopyranose, efficiently derived from L-ascorbic acid, were
      individually used as a starting unit and an elongation unit to prepare L
      guluronic acid linked alginate oligosaccharides in excellent alpha selectivity
      and in good yields.

PMID- 19097130
TI  - Telomerization of butadiene with glycerol: reaction control through process
      engineering, solvents, and additives.
AB  - Owing to the large amount of glycerol that is formed as a by-product during
      biodiesel production, there have been great efforts to develop new reactions and
      processes based on glycerol as a renewable feedstock. One example is the
      telomerization of butadiene with glycerol which provides an atom-economic route
      to amphiphilic molecules. The reaction is catalyzed by homogeneous palladium
      catalysts which necessitates efficient catalyst recycling. By employing an
      aqueous biphasic system, an increased selectivity towards the desired mono-ethers
      was observed in the telomerization reaction. The performance of the reaction and
      separation and recycling of the catalyst were optimized by the addition of
      organic solvents as well as cyclodextrins. By adding cyclodextrins, the
      conversion of glycerol could be increased and the leaching of palladium could be
      reduced. Leaching of palladium into the organic phase could be lowered also by
      using 2-octanol or 2-propanol as additional solvents. Furthermore, the catalyst
      system could be stabilized by adding nitriles or phosphonium salts, and radical
      polymerization, which leads to fouling, could be inhibited successfully.

PMID- 19097131
TI  - Catalysts for solar water splitting.

PMID- 19097132
TI  - Transcriptional up-regulation of FoxM1 in response to hypoxia is mediated by HIF
      1.
AB  - The proliferation-specific Forkhead box M1 (FoxM1) transcription factor is
      overexpressed in cancer cells and acts as an important regulator of cancer cell
      growth and survival. Here, we show the molecular mechanisms by which hypoxia
      regulate FoxM1 expression in cancer cells. When cells were subjected to hypoxia
      (1% O2), the mRNA and protein levels of FoxM1 had a significant increase in
      cancer cells (HepG2, MCF-7, and HeLa). Such increase was due to the direct
      binding of hypoxia-inducible factor 1 (HIF-1) to the HIF-1 binding sites in the
      FoxM1 promoter. By deletion and mutation assays, we demonstrated that the HIF1-1
      and HIF1-3/4 binding sites on the FoxM1 promoter were essential for
      transcriptional activation of FoxM1 by hypoxia. We also demonstrated that HIF
      1alpha directly bound to the promoter of FoxM1 and the binding was specific, as
      revealed by HIF-1 binding/competition assay and chromatin immunoprecipitation
      assay. Consequently, the up-regulation of FoxM1 accelerated the growth of hypoxic
      cancer cells by decreasing nuclear levels of p21 and increasing expression of
      cyclin B1 and cyclin D1. These findings provide a new insight into how tumor
      cells overcome hypoxic stress and survive, and also disclose a new regulatory
      mechanism of FoxM1 expression in tumor cells.

PMID- 19097133
TI  - Aberrant regulation and modification of heat shock factor 1 in senescent human
      diploid fibroblasts.
AB  - Induction of the heat shock response (HSR), determined by hsp70-luciferase
      reporter and HSP70 protein expression, is attenuated as a function of age of the
      IMR-90 human diploid fibroblasts. To better understand the underlying mechanism,
      we evaluated changes in the regulation and function of the HSF1 transcription
      factor. We show that the activation of HSF1 both in vivo and in vitro was
      decreased as a function of age, and this was attributable to a change in the
      regulation of HSF1 as the abundance of HSF1 protein and mRNA was unaffected. HSF1
      was primarily cytosolic in young cells maintained at 37 degrees C, and heat shock
      promoted its quantitative nuclear translocation and trimerization. In old cells,
      some HSF1 was nuclear sequestered at 37 degrees C, and heat shock failed to
      promote the quantitative trimerization of HSF1. These changes in HSF1 could be
      reproduced by treating young cells with H2O2 to stunt them into premature
      senescence. Flow cytometry measurement of peroxide content showed higher levels
      in old cells and H2O2-induced premature senescent cells as compared to young
      cells. Experiments using isoelectric focusing and Western blot showed age
      dependent changes in the mobility of HSF1 in a pattern consistent with its S
      glutathiolation and S-nitrosylation; these changes could be mimicked by treating
      young cells with H2O2. Our results demonstrated dynamic age-dependent changes in
      the regulation but not the amount of HSF1. These changes are likely mediated by
      oxidative events that promote reversible and irreversible modification of HSF1
      including S-glutathiolation and S-nitrosylation.

PMID- 19097134
TI  - Lanthanum and its rapidly emerging role as an anti-carcinogenic agent.

PMID- 19097135
TI  - Experimental and quantum-chemical studies of 1H, 13C and 15N NMR coordination
      shifts in Au(III), Pd(II) and Pt(II) chloride complexes with picolines.
AB  - (1)H, (13)C and (15)N NMR studies of gold(III), palladium(II) and platinum(II)
      chloride complexes with picolines, [Au(PIC)Cl(3)], trans-[Pd(PIC)(2)Cl(2)],
      trans/cis-[Pt(PIC)(2)Cl(2)] and [Pt(PIC)(4)]Cl(2), were performed. After
      complexation, the (1)H and (13)C signals were shifted to higher frequency,
      whereas the (15)N ones to lower (by ca 80-110 ppm), with respect to the free
      ligands. The (15)N shielding phenomenon was enhanced in the series [Au(PIC)Cl(3)]
      < trans-[Pd(PIC)(2)Cl(2)] < cis-[Pt(PIC)(2)Cl(2)] < trans-[Pt(PIC)(2)Cl(2)]; it
      increased following the Pd(II) --> Pt(II) replacement, but decreased upon the
      trans --> cis-transition. Experimental (1)H, (13)C and (15)N NMR chemical shifts
      were compared to those quantum-chemically calculated by B3LYP/LanL2DZ + 6
      31G**//B3LYP/LanL2DZ + 6-31G*.

PMID- 19097137
TI  - Proteomic analysis of mitochondrial proteins of basal and lipolytically
      (isoproterenol and TNF-alpha)-stimulated adipocytes.
AB  - The regulation of adipocyte lipolysis is increasingly believed to influence
      insulin resistance, in a process that may be associated with mitochondrial
      dysfunction. However, the molecular basis of the relationship between
      mitochondrial protein expression, lipolytic responsiveness, and insulin
      resistance remains unknown. A set of proteins that shows altered abundances in
      the mitochondria of untreated and treated 3T3-L1 adipocytes with TNF-alpha or
      isoproterenol was identified. These include the proteins associated with energy
      production, including fatty acid oxidation, TCA cycle, and oxidative
      phosphorylation. Proteins associated with oxidative stress dissipation were down
      regulated in lipolytically stimulated adipocytes. Lipolytic stimulation with
      isoproterenol and TNF-alpha, which is also a potent proinflammatory cytokine,
      showed some noticeable differences in mitochondrial protein expression. For
      example, isoproterenol markedly enhanced the expression of prohibitin which is
      involved in the integrity of mitochondria but TNF-alpha did not. These results
      provide valuable information on mitochondrial dysfunction associated with
      oxidative stress induced by lipolytic stimulation.

PMID- 19097136
TI  - A transgenic red fluorescent protein-expressing nude mouse for color-coded
      imaging of the tumor microenvironment.
AB  - The tumor microenvironment (TME) is critical for tumor growth and progression. We
      have previously developed color-coded imaging of the TME using a green
      fluorescent protein (GFP) transgenic nude mouse as a host. However, most donor
      sources of cell types appropriate for study in the TME are from mice expressing
      GFP. Therefore, a nude mouse expressing red fluorescent protein (RFP) would be an
      appropriate host for transplantation of GFP-expressing stromal cells as well as
      double-labeled cancer cells expressing GFP in the nucleus and RFP in the
      cytoplasm, thereby creating a three-color imaging model of the TME. The RFP nude
      mouse was obtained by crossing non-transgenic nude mice with the transgenic
      C57/B6 mouse in which the beta-actin promoter drives RFP (DsRed2) expression in
      essentially all tissues. In crosses between nu/nu RFP male mice and nu/+ RFP
      female mice, the embryos fluoresced red. Approximately 50% of the offspring of
      these mice were RFP nude mice. In the RFP nude mouse, the organs all brightly
      expressed RFP, including the heart, lungs, spleen, pancreas, esophagus, stomach,
      duodenum, the male and female reproductive systems; brain and spinal cord; and
      the circulatory system, including the heart, and major arteries and veins. The
      skinned skeleton highly expressed RFP. The bone marrow and spleen cells were also
      RFP positive. GFP-expressing human cancer cell lines, including HCT-116-GFP colon
      cancer and MDA-MB-435-GFP breast cancer were orthotopically transplanted to the
      transgenic RFP nude mice. These human tumors grew extensively in the transgenic
      RFP nude mouse. Dual-color fluorescence imaging enabled visualization of human
      tumor-host interaction. The RFP nude mouse model should greatly expand our
      knowledge of the TME.

PMID- 19097138
TI  - Evaluation of rosiglitazone administration on cardiovascular function in severe
      obesity.
AB  - BACKGROUND: Obese patients have myocardial structural and functional alterations
      related to insulin resistance. HYPOTHESIS: The purpose of the study was to
      analyze the effects of rosiglitazone, an insulin sensitizer agent, on cardiac
      morphometry and functioning. METHODS: In 2 groups of sex- and age-matched,
      nondiabetic, obese patients (5 men and 7 women, age 19-51 y; group A: body mass
      index [BMI] 40.6 +/- 3.4 kg/m(2); group B: BMI 42.6 +/- 2.7 kg/m(2)), we
      evaluated the basal insulin sensitivity index (HOMA[IS]), body composition by
      bioelectrical impedance analysis and 24-h blood pressure monitoring. Furthermore,
      all patients underwent conventional 2-Dimensional and color Doppler
      echocardiography, and pulsed-wave tissue Doppler imaging (TDI). After the
      baseline evaluation, all patients were put on a hypocaloric diet (70% basal
      metabolic rate) plus placebo if they were in group A, or plus rosiglitazone (4 mg
      twice daily; Avandia [GlaxoSmithKline plc., Brentford, Middlesex, United
      Kingdom]) if they were in group B, for 6 mo. RESULTS: Significant decreases in
      body weight, total fat mass, BMI, and systolic blood pressure were registered in
      both groups. Rosiglitazone administration appeared more efficient in improving
      HOMA(IS) (mean difference: 0.30 +/- 0.19 versus 0.11 +/- 0.21, p < 0.05). Left
      ventricular (LV) diastolic diameter (49.4 +/- 7.7 versus 52.3 +/- 5.4 mm, p <
      0.05) and E wave (0.89 +/- 0.18 versus 0.99 +/- 0.20 m/sec, p < 0.05) increased
      in the rosiglitazone group due to a rise in preload and water content without
      peripheral edema. The increase in systolic (Sa) wave velocity in both groups was
      probably a result of the general improvement in insulin metabolism and the
      decrease in blood pressure. CONCLUSIONS: We confirmed the positive effect of
      rosiglitazone on glucose metabolism in obese, nondiabetic patients, but changes
      in insulin sensitivity did not explain the cardiac effects produced by further
      mechanisms.

PMID- 19097139
TI  - Beyond the psychotherapy and survival debate: the challenge of social disparity,
      depression and treatment adherence in psychosocial cancer care.
AB  - The psychotherapy and cancer survival debate generated great interest in the
      psychoneuroimmunological and bio-behavioral mechanisms that might mediate any
      gain in survival. Recent methodologically-improved cognitive-existential,
      supportive-expressive and psycho-educational group interventions for patients
      with breast cancer and melanoma have not extended survival times. Shorter
      survival has been associated with social disparity and untreated clinical
      depression, potentially mediated by poorer adherence to anti-cancer treatments.
      Group therapy both prevents and treats depression. Future research could address
      these bio-behavioral mechanisms.

PMID- 19097140
TI  - Promoting evidence-based psychosocial care for cancer patients.
AB  - With numerous studies demonstrating that psychosocial care reduces distress and
      improves quality of life, practitioners have an obligation to treat cancer
      patients in a manner consistent with this evidence. Although the rationale is
      straightforward, major challenges exist in achieving the goal of translating
      research into clinical practice. One challenge has been the nature of the
      evidence, with many studies of psychosocial interventions characterized by poor
      methodological quality, absence of eligibility criteria specifying heightened
      distress, and minimal consideration of dissemination potential. A second
      challenge has been to make practitioners aware of relevant evidence. Targeted
      efforts at dissemination, such as the issuance of clinical practice guidelines
      and evidence-based recommendations and the distribution of intervention materials
      via the Internet, appear to be more effective than passive efforts in providing
      practitioners with useful information. Perhaps the most challenging aspect has
      been to persuade practitioners to change how they practice. One approach
      currently under development would allow practitioners and health-care
      organizations to perform self-evaluations of the quality of their psychosocial
      care based on review of medical records. Feedback showing quality of care to be
      less than optimal is likely to motivate change, especially if the quality
      indicators assessed are considered to be important and reliable and point to
      specific actions that can be taken. The use of evidence to promote changes in
      clinical practice represents one of the major ways in which the field of psycho
      oncology can fully realize its potential to positively affect the lives of people
      with cancer.

PMID- 19097141
TI  - Modulation of muscle rNaV1.4 Na+ channel isoform by arachidonic acid and its non
      metabolized analog.
AB  - Arachidonic acid (AA) and its metabolic products are important second messengers
      which exert many biological actions, including modulation of various ion
      channels. However, the blockage of muscle Na(+) channel isoforms by AA has not
      been examined in detail. Here, we investigated the modulating effects of AA on
      muscle rNa(V)1.4 isoforms expressed in human embryonic kidney 293 cells. The
      results revealed that AA has both activation and inhibitory effects on rNa(V)1.4
      currents depending on the depolarizing potential: AA increased the rNa(V)1.4
      current evoked by a depolarization of -30 or -40 mV, but significantly decreased
      the rNa(V)1.4 current evoked by a depolarization of membrane potential over -10
      mV. At concentrations of 1-500 microM, the inhibitory effect on the rNa(V)1.4
      current induced by AA was dose-dependent and reversible. In addition to
      modulating the amplitude of the rNa(V)1.4 current, AA significantly modulated the
      steady-state activation and inactivation properties of rNa(V)1.4 channels.
      Furthermore, treatment with AA resulted in a fairly slow recovery of the
      rNa(V)1.4 channel from inactivation; however, the inhibitory effect of AA was not
      changed by repetitive pulses or by changing frequency. The effect of AA on
      rNa(V)1.4 currents was completely mimicked by ETYA, the non-metabolized analog of
      AA. Our data demonstrated that AA, but not the metabolic products of AA, can
      voltage-dependent modulate rNa(V)1.4 currents.

PMID- 19097142
TI  - Nuclear matrix binding site in the Rad51 recombinase.
AB  - It has been shown that the key homologous recombination protein Rad51 accumulates
      in DNA damage-induced nuclear foci that are attached to the nuclear matrix. In
      the present communication we attempted to find whether Rad51 contains a
      functional domain responsible for nuclear matrix binding. By alignments of the
      sequences encoding nuclear matrix targeting signals of human nuclear matrix
      binding proteins with the whole length human Rad51sequence a putative nuclear
      matrix targeting signal was identified. To prove that it is responsible for the
      nuclear matrix association of Rad51 18 base pairs encoding a cluster of
      hydrophobic amino acids in the human Rad51 Flag-tagged gene were deleted. The
      formation of damage-induced Rad51 foci and their association with the nuclear
      matrix were monitored in HeLa cells transfected with the wild-type and the
      mutated Rad51gene after treatment with mitomycin C. The results showed that while
      the wild-type protein formed Rad51 foci attached to the nuclear matrix, the
      mutated Rad51 failed to form DNA damage-induced nuclear foci. The loss of foci
      formation activity of the mutated protein was not due to impaired ability to bind
      double-stranded DNA in an ATP-dependent way in vitro and to bind chromatin in
      vivo. These data suggest that the assembly of Rad51 into nuclear foci is assisted
      by association with the nuclear matrix, which may support the spatial
      organization of the process of repair by homologous recombination.

PMID- 19097144
TI  - Impact of varying electron donors on the molecular microbial ecology and
      biokinetics of methylotrophic denitrifying bacteria.
AB  - The goal of this study was to identify bacterial populations that assimilated
      methanol in a denitrifying sequencing batch reactor (SBR), using stable isotope
      probing (SIP) of (13)C labeled DNA and quantitatively track changes in these
      populations upon changing the electron donor from methanol to ethanol in the SBR
      feed. Based on SIP derived (13)C 16S rRNA gene clone libraries, dominant SBR
      methylotrophic bacteria were related to Methyloversatilis spp. and Hyphomicrobium
      spp. These methylotrophic populations were quantified via newly developed real
      time PCR assays. Upon switching the electron donor from methanol to ethanol,
      Hyphomicrobium spp. concentrations decreased significantly in accordance with
      their obligately methylotrophic nutritional mode. In contrast, Methyloversatilis
      spp. concentrations were relatively unchanged, in accordance with their ability
      to assimilate both methanol and ethanol. Direct assimilation of ethanol by
      Methyloversatilis spp. but not Hyphomicrobium spp. was also confirmed via SIP.
      The reduction in methylotrophic bacterial concentration upon switching to ethanol
      was paralleled by a significant decrease in the methanol supported
      denitrification biokinetics of the SBR on nitrate. In sum, the results of this
      study demonstrate that the metabolic capabilities (methanol assimilation and
      metabolism) and substrate specificity (obligately or facultatively
      methylotrophic) of two distinct methylotrophic bacterial populations contributed
      to their survival or washout in denitrifying bioreactors.

PMID- 19097143
TI  - IL-1 beta induces urokinase-plasminogen activator expression and cell migration
      through PKC alpha, JNK1/2, and NF-kappaB in A549 cells.
AB  - Breakdown of the extracellular matrix (ECM) is accomplished by the concerted
      action of several proteases, including the urokinase plasminogen-activator (uPA)
      system and matrix metalloproteinases (MMPs), which is crucial for cancer invasion
      and metastasis. Several reports have shown that the levels of IL-1 beta and MMPs
      in plasma of the patients with lung cancer are significantly elevated and link to
      the invasion of tumor cells. Therefore, we investigated whether IL-1 beta-induced
      expression of uPA participated in lung cancer progression. In this study, IL-1
      beta significantly induced uPA expression and activity via PKC alpha-dependent
      JNK1/2 and NIK cascades, linking to IKK alpha/beta activation, p65 translocation
      and transcription activity, using pharmacological inhibitors and transfection
      with dominant negative mutants and siRNAs. IL-1 beta-induced uPA protein and mRNA
      expression in a time- and concentration-dependent manner, which was inhibited by
      pretreatment with the inhibitors of JNK1/2 (SP600125), PKC (Ro31-8220, Go6976),
      or NF-kappaB (helenalin), and transfection with dominant negative mutants of PKC
      alpha, NIK, and IKK beta, and siRNAs of JNK1/2 and p65. IL-1 beta stimulated PKC
      alpha translocation to plasma membrane leading to phosphorylation of JNK1/2,
      which was attenuated by PKC inhibitors and transfection with shRNAs of JNK1/2,
      but not by helenalin. In addition, IL-1beta stimulated p65 phosphorylation and
      translocation into nucleus concomitant with I kappaB alpha phosphorylation and I
      kappaB alpha degradation, which was mediated via activation of PKC alpha
      dependent JNK1/2-NIK/IKK beta cascade. These results demonstrated that in A549
      cells, activation of p50/p65 heterodimer through sequential activation of PKC
      alpha-JNK-NIK-IKK beta-NF-kappaB was required for IL-1 beta-induced uPA
      expression associated with migration of tumor cells.

PMID- 19097145
TI  - Provider networks and primary-care signups: do they restrict the use of medical
      services?
AB  - This article analyzes the effect of gatekeeper and network restrictions on use of
      health-care services using simulation-based estimation methods. Data from the
      Community Tracking Survey (1996-1997) show significant evidence of selection into
      plans with gatekeeper and/or network restrictions. Enrollees in plans with
      networks of physicians have fewer office-based visits to non-physician medical
      professionals, but more emergency room visits and hospital stays. Individuals in
      plans that require signups with a primary-care provider have more visits to non
      physician providers of care, more surgeries and hospital stays but substantially
      fewer emergency room visits. Enrollees of plans that do not pay for out-of
      network services have more office-based and emergency room visits, but less
      surgeries and hospitalizations.

PMID- 19097146
TI  - A thermosensitive chitosan/poly(vinyl alcohol) hydrogel containing hydroxyapatite
      for protein delivery.
AB  - The synthesis and characterization of a thermosensitive chitosan/poly(vinyl
      alcohol) (PVA) hydrogel containing hydroxyapatite for protein delivery were first
      reported. Two synthetic processes were introduced, that is, in situ and ex situ
      routes. Fourier-transform infrared spectroscopy (FTIR), X-ray diffraction (XRD),
      scanning electron microscopy (SEM), and rheological analysis were employed to
      characterize the hydrogel. The gel formation decreased the crystallinity of the
      hydroxyapatite crystal. FTIR results showed that the hydroxyapatite crystals were
      partially substituted by carbonate. It was supposed that the structural features
      of hydroxyapatite were close to those of biological apatites. The thermosensitive
      property of the gels was evaluated by rheological analysis, which indicated that
      the strength of hydroxyapatite-chitosan/PVA composite gels was notably enhanced
      in comparison with that of pure chitosan/PVA gel, especially for hydroxyapatite
      chitosan/PVA composite gels synthesized through the in situ process. The
      performances of composite gels containing different amounts of hydroxyapatite
      were further studied. For the hydroxyapatite-chitosan/PVA composite gels
      containing 0.1 mM hydroxyapatite synthesized through in situ process, the
      swelling degree was the lowest, and the speed of protein release was the slowest.
      Therefore, the composite gels are attractive for applications as protein
      delivery, artificial bones, and scaffolds for tissue engineering.

PMID- 19097147
TI  - Minor pathological changes are induced by naltrexone-poly(DL-lactide) implants in
      pregnant rats.
AB  - Oral naltrexone is used to treat alcohol and heroin dependence but is associated
      with poor patient compliance. Sustained-release preparations have been developed
      to overcome noncompliance. Many sustained-release preparations are composed of
      polymers combined with naltrexone. Limited data indicate that polymers induce
      variable levels of tissue reactivity and that naltrexone may increase this
      effect. A slow-release subcutaneous naltrexone-poly (DL-lactide) implant is
      currently being trialed to treat heroin dependence in Western Australia. A
      minority of women fall pregnant and, although tissue reactivity in nonpregnant
      humans is relatively minor, detailed chronological data during pregnancy are
      lacking. Histological changes in pregnant rats were assessed; a single active
      tablet containing poly[trans-3,6-dimethyl-1,4-dioxyane-2,5-dione] (DL-lactide)
      loaded with 25 mg of naltrexone was implanted subcutaneously, and tissue response
      was compared with inactive polymer implantation. Rats were timed mated at 13-26
      days postimplant. Tissue assessment up to 75 days by a pathologist showed that
      naltrexone induced chronic inflammatory response in a dose-dependent manner,
      although still at a low level. Furthermore, for inactive implants, minimal
      foreign body reaction and fibrosis, together with low-level inflammation,
      suggested good long-term biocompatibility. We conclude that the Australian
      naltrexone-poly(DL-lactide) implant is tolerated in pregnant rats, reinforcing
      its potential role for managing alcohol and heroin dependence in pregnant humans.

PMID- 19097149
TI  - Correlation between rate of bony ingrowth to stainless steel, pure titanium, and
      titanium alloy implants in vivo and formation of hydroxyapatite on their surfaces
      in vitro.
AB  - The rate of bony ingrowth to identical metal implants made of either pure
      titanium (cpTi), titanium alloy (Ti-6Al-4V), or stainless steel 316L (SS)
      inserted to the medullar canal of the femur in rats was investigated. The
      kinetics of spontaneous deposition of hydroxyapatite (HA) globules on the
      aforementioned metals in vitro during incubation in simulated body fluid (SBF)
      was also studied. It was found that the rate of increased bonding strength
      between the cpTi implants and the host bone was the highest, whereas around the
      SS implants it was the slowest. At 10 days postimplant insertion, the shear
      strength of the cpTi implants was 2.2- and 4-fold significantly higher than for
      the Ti-6Al-4V and the SS implants, respectively. Spontaneous formation of the HA
      globules on the cpTi and Ti-6Al-4V implants that were incubated in the SBF was
      observed as early as 6 and 10 days after incubation in SBF, respectively, whereas
      on SS implants, deposition of HA was evident only after 2 weeks of in vitro
      incubation in SBF. It is concluded that the chemical surface characteristics and
      the biocompatibility of the implants probably play a key role in the process of
      bone growth next to them, during the formation of bone in vivo. The rate of bony
      ingrowth to various metal implants alloys inserted into the medullar canal of
      rats correlates well with the induction of apatite formation on them during
      incubation in vitro with SBF.

PMID- 19097148
TI  - Modulated release of OP-1 and enhanced preosteoblast differentiation using a core
      shell nanoparticulate system.
AB  - A release-controlled OP-1 delivery system consisting of a suspension of core
      shell nanoparticles was prepared. The nanoparticles were composed of a core of
      positively-charged large unilamellar liposomes and a shell constructed through
      the L-b-L assembly of alternating layers of negatively-charged sodium alginate
      and positively-charged chitosan. Cytotoxicity was assayed with MC3T3-E1.4 mouse
      preosteoblast cells and cell viability was determined by colorimetry (CellQuanti
      MTT kit). The system was loaded with a range of OP-1 concentrations and the
      release profiles were obtained and fitted into the Higuchi model to determine
      release kinetics. Alkaline phosphatase (ALP) activity of preosteoblasts was
      evaluated using a micro-BCA assay. The resulting monodisperse and nontoxic
      spherical nanoparticles exhibited high physical stability in simulated
      physiological media as well as an extended shelf-life allowing for immediate
      protein loading before future administration. ALP activity increased over time
      with the OP-1 loaded delivery system when compared with control, protein alone,
      and nanoparticles alone (p < 0.05). The system offers copious compartments for
      protein entrapment including the aqueous core and within the polyelectrolyte
      layers in the shell and demonstrates a sustained triphasic linear release of OP-1
      over a prolonged period of 45 days, in vitro. This system offers a great
      advantage for optimum growth factor performance when applied in different
      anatomical sites of varying defect sizes and vascularity.

PMID- 19097150
TI  - Sox9 expression of alginate-encapsulated chondrocytes is stimulated by low cell
      density.
AB  - Recent research in tissue engineering for the treatment of cartilage defects have
      demonstrated that matrix-biomaterial, cell culture conditions, and cytokine
      related factors influence the chondrogenic differentiation pattern, especially
      for the expression of matrix genes. However, little is known about the impact of
      cell seeding density in a three-dimensional environment on the key chondrogenic
      transcription factor Sox9. Here we investigated, whether the cell concentration
      of alginate encapsulated chondrocytes influences the Sox9 expression.
      Dedifferentiated passage-4 porcine chondrocytes were encapsulated in alginate
      beads at two different concentrations (4 x 10(6) versus 7 x 10(7) cells/mL) and
      cultivated for up to 4 weeks under TGF-ss stimulation. The expression of Sox9,
      Collagen I, II, and X was assessed via quantitative RT-PCR and compared to those
      observed in the initial monolayer culture. Cellular viability, cell morphology,
      and the sulphated glycosaminoglycan-production were monitored. Interestingly Sox9
      expression was significantly upregulated in the low-cell-density group, whereas
      no difference between high-cell-density and monolayer culture group could be
      observed. Furthermore, the cellular survival and the sulphated glycosaminoglycan
      production were higher in the low-cell-density group. Collagen I expression was
      downregulated in the low-cell-density group whereas it was upregulated in the
      high-cell-density one. Surprisingly, only the high-cell-density group showed the
      expression of Collagen II, although it appeared not significant. Collagen X
      expression was upregulated in the low-cell-density group. Taken together our data
      indicate that a low concentration of cell seeding in a three-dimensional
      environment is beneficial for the overall chondrogenic development. However, this
      article reveals discrepancies between Sox9 and the chondrogenic pathway in
      redifferentiating chondrocytes that should be addressed in further work.

PMID- 19097151
TI  - The behavior of mesenchymal stem cells on micropatterned PLLA membranes.
AB  - The aim of this study was to evaluate the behaviors of mesenchymal stem cells
      (MSCs) on Poly(L-Lactic acid) (PLLA) membranes with different surface
      topographies. The double-sided micropatterns, island-patterned, and sunken
      patterned PLLA membranes with diameters of 60 and 100 microm, were fabricated by
      the soft lithography method. The cell viability of MSCs on the island- and sunken
      patterned PLLA membranes were characterized by scanning electron microscopy
      (SEM), MTT assay, and flow cytometric analysis. Cell adhesion and proliferation
      capability were superior for the MSCs seeding on the island-patterned PLLA
      membranes than those on the sunken-patterned PLLA membranes. Especially, we
      observed the best biocompatibility for MSCs on the island-patterned surface with
      diameter of 100 microm. In addition, the improvement of cell attachment and
      augmenting subsequent cellular response are investigated after the island
      patterned membranes precoating with collagen and fibronectin. Furthermore, the
      flow cytometric analysis reveals the MSCs can expand and maintain the phenotype
      on these PLLA membranes without losing its potential for differentiation. Since
      scale-up of cell production and optimization of culture conditions are important
      for stem cell engineering, to control the stem cell proliferation and
      differentiation is necessary. Therefore, besides topographical properties play a
      crucial role on the stem cells attachment and proliferative activity, it is
      suggested that the "relative scale" between cell and pattern also affects the
      cell adhesion morphologies and cell behaviors. Based on the overall cellular
      response, this study provides a valuable guidance to prepare appropriate
      topographic surface for tissue engineering application.

PMID- 19097152
TI  - Osteogenic differentiation of human mesenchymal stem cells on poly(ethylene
      glycol)-variant biomaterials.
AB  - This study evaluated the osteogenic differentiation of human mesenchymal stem
      cells (MSCs), on tyrosine-derived polycarbonates copolymerized with poly(ethylene
      glycol) (PEG) to determine their potential as a scaffold for bone tissue
      engineering applications. The addition of PEG in the backbone of polycarbonates
      has been shown to alter mechanical properties, degradation rates, degree of
      protein adsorption, and subsequent cell adhesion and motility in mature cell
      phenotypes. Its effect on MSC behavior is unknown. MSC morphology, motility,
      proliferation, and osteogenic differentiation were evaluated on polycarbonates
      containing 0-5% PEG over a 14 day culture. MSCs on polycarbonates containing 0%
      or 3% PEG content upregulated the expression of osteogenic markers as
      demonstrated by alkaline phosphatase activity and osteocalcin expression although
      at different stages in the 14 day culture. Cells on polycarbonates containing no
      PEG were characterized as having early onset of cell spreading and osteogenic
      differentiation. Cells on 3% PEG surfaces were delayed in cell spreading and
      osteogenic differentiation, but had the highest motility as compared with cells
      on substrates containing no PEG and substrates containing 5% PEG at early time
      points. Throughout the culture, cells on polycarbonates containing 5% PEG had the
      lowest levels of osteogenic markers, displayed poor cell-substrate adhesion, and
      established cell-cell aggregates. Thus, designing substrates with minute
      variations in PEG may serve as a tool to guide MSC adhesion and motility
      accompanying osteogenic differentiation, and may be beneficial for abundant bone
      tissue formation in vivo.

PMID- 19097153
TI  - Influence of topography of nanofibrils of three-dimensional collagen gel beads on
      the phenotype, proliferation, and maturation of osteoblasts.
AB  - Our objectives were to fabricate three-dimensional collagen/chondroitin sulfate
      beads using mild conditions and no chemical reagents, and subsequently to
      investigate the influence of the nanotopography of these beads on primary
      osteoblast and MG63 cell responses, including cell morphology, proliferation
      rate, and gene expression. The major principle used to prepare beads was complex
      coacervation, with which we could obtain a three-dimensional collagen matrix with
      or without a characteristic D-pattern. Therefore, we utilized primary osteoblasts
      and MG63, an osteoblast-like cell line, to examine the effects of specific
      structures on cellular behaviors. We found that the phenotype of primary
      osteoblasts grown on D-periodic beads was a polygonal shape with extending
      lamellipodia; however, a greater number of cells displayed a circular morphology
      on the non-D-periodic carriers. After 7 and 14 days, MG63 cells on D-periodic
      beads expressed higher levels of osteopontin, alkaline phosphatase activity, type
      I collagen, and osteocalcin than those on the non-D-periodic beads. Together,
      these data demonstrate that the unique D-pattern of collagen not only enhances
      the gene expression and mineralization of osteoblasts but also induces the cells
      to display the normal phenotype, which indicates that the nanotopography of
      carriers may regulate cellular responses through the spatial control of
      downstream signaling.

PMID- 19097154
TI  - Oxygen diffusivity of biologic and synthetic scaffold materials for tissue
      engineering.
AB  - Scaffolds for tissue engineering and regenerative medicine applications are
      commonly manufactured from synthetic materials, intact or isolated components of
      extracellular matrix (ECM), or a combination of such materials. After surgical
      implantation, the metabolic requirements of cells that populate the scaffold
      depend upon adequate gas and nutrient exchange with the surrounding
      microenvironment. The present study measured the oxygen transfer through three
      biologic scaffold materials composed of ECM including small intestinal submucosa
      (SIS), urinary bladder submucosa (UBS), and urinary bladder matrix (UBM), and one
      synthetic biomaterial, Dacron. The oxygen diffusivity was calculated from Fick's
      first law of diffusion. Each material permitted measurable oxygen diffusion. The
      diffusivity of SIS was found to be dependent on the direction of oxygen transfer;
      the oxygen transfer in the abluminal-to-luminal direction was significantly
      greater than the luminal-to-abluminal direction. The oxygen diffusivity of UBM
      and UBS were similar despite the presence of an intact basement membrane on the
      luminal surface of UBM. Dacron showed oxygen diffusivity values seven times
      greater than the ECM biomaterials. The current study showed that each material
      has unique oxygen diffusivity values, and these values may be dependent on the
      scaffold's ultrastructure.

PMID- 19097155
TI  - Effects of Schwann cell alignment along the oriented electrospun chitosan
      nanofibers on nerve regeneration.
AB  - We have constructed a chitosan nonwoven nanofiber mesh tube consisting of
      oriented fibers by the electrospinning method. The efficacy of oriented
      nanofibers on Schwann cell alignment and positive effect of this tube on
      peripheral nerve regeneration were confirmed. The physical properties of the
      chitosan nanofiber mesh sheets prepared by electrospinning with or without fiber
      orientation were characterized. Then, immortalized Schwann cells were cultured on
      these sheets. Furthermore, the chitosan nanofiber mesh tubes with or without
      orientation, and bilayered chitosan mesh tube with an inner layer of oriented
      nanofibers and an outer layer of randomized nanofibers were bridgegrafted into
      rat sciatic nerve defect. As a result of fiber orientation, the tensile strength
      along the axis of the sheet increased. Because Schwann cells aligned along the
      nanofibers, oriented fibrous sheets could exhibit a Schwann cell column.
      Functional recovery and electrophysiological recovery occurred in time in the
      oriented group as well as in the bilayered group, and approximately matched those
      in the isograft. Furthermore, histological analysis revealed that the sprouting
      of myelinated axons occurred vigorously followed by axonal maturation in the
      isograft, oriented, and bilayered group in the order. The oriented chitosan
      nanofiber mesh tube may be a promising substitute for autogenous nerve graft.

PMID- 19097156
TI  - Identification of calcification with MRI using susceptibility-weighted imaging: a
      case study.
AB  - Susceptibility weighted imaging (SWI) is a new MRI technique that can identify
      calcification by using phase images. We present a single case with a partially
      calcified oligodendroglioma, multiple calcified cysticercosis lesions, and
      multiple physiologic calcifications in the same patient. SWI phase images and
      computed tomography (CT) images are compared. SWI phase images showed the same
      calcified lesions as shown on CT and sometimes some new calcifications. Our
      conclusion is that SWI filtered phase images can identify calcifications as well
      as CT in this case.

PMID- 19097157
TI  - Biomimetic control of vascular smooth muscle cell morphology and phenotype for
      functional tissue-engineered small-diameter blood vessels.
AB  - Small-diameter blood vessel substitutes are urgently needed for patients
      requiring replacements of their coronary and below-the-knee vessels and for
      better arteriovenous dialysis shunts. Circulatory diseases, especially those
      arising from atherosclerosis, are the predominant cause of mortality and
      morbidity in the developed world. Current therapies include the use of autologous
      vessels or synthetic materials as vessel replacements. The limited availability
      of healthy vessels for use as bypass grafts and the failure of purely synthetic
      materials in small-diameter sites necessitate the development of a biological
      substitute. Tissue engineering is such an approach and has achieved promising
      results, but reconstruction of a functional vascular tunica media, with
      circumferentially oriented contractile smooth muscle cells (SMCs) and
      extracellular matrix, appropriate mechanical properties, and vasoactivity has yet
      to be demonstrated. This review focuses on strategies to effect the switch of SMC
      phenotype from synthetic to contractile, which is regarded as crucial for the
      engineering of a functional vascular media. The synthetic SMC phenotype is
      desired initially for cell proliferation and tissue remodeling, but the
      contractile phenotype is then necessary for sufficient vasoactivity and
      inhibition of neointima formation. The factors governing the switch to a more
      contractile phenotype with in vitro culture are reviewed.

PMID- 19097158
TI  - A theoretical structural analysis of the factors that affect (1)J(NH), (1h)J(NH)
      and (2h)J(NN) in N-H...N hydrogen-bonded complexes.
AB  - Calculations of (1)J(NH), (1h)J(NH) and (2h)J(NN) spin-spin coupling constants of
      27 complexes presenting N-H...N hydrogen bonds have allowed to analyze these
      through hydrogen-bond coupling as a function of the hybridization of both
      nitrogen atoms and the charge (+1, 0, - 1) of the complex. The main conclusions
      are that the hybridization of N atom of the hydrogen bond donor is much more
      important than that of the hydrogen bond acceptor. Positive and negative charges
      (cationic and anionic complexes) exert opposite effects while the effect of the
      transition states 'proton-in-the-middle' is considerable.

PMID- 19097159
TI  - Evaluation of impaction force of nasal sprays and metered-dose inhalers using the
      Texture Analyser.
AB  - The impaction force from an inhalation product is an important characteristics by
      which to characterize the spray plume. It is one of the plume characteristics
      that can be perceived by a patient, and is expected to be good measures of local
      delivery equivalence for inhalation drugs. A Stable Micro Systems TA-XT.plus
      Texture Analyser equipped with 750 g load cell was used to measure the impaction
      force of several nasal sprays and metered-dose inhalers (MDIs). A survey of
      several commercial nasal spray and MDI products shows that impaction forces of
      these products varies from 1.5 to 6.5 g force and are significantly different
      from each other. A 3-level, 4-factor Box-Behnken design was applied to the study
      of impaction force of nasal sprays using placebo solutions. The influences of
      four factors: actuation stroke length, actuation velocity, concentration of
      gelling agent, and concentration of surfactant, were investigated. Of those
      factors examined here, actuation velocity exerts the greatest effect on impaction
      force. Impaction force is a discriminative parameter for in vitro testing of
      nasal spray and MDI products. Since impaction force is more directly related to
      patient sensation and aerosol deposition in the nasal mucus than other, more
      traditional parameters, it may provide a better way to evaluate in vitro
      equivalence in support of abbreviated new drug applications (ANDAs) for orally
      inhaled and nasal drug products.

PMID- 19097161
TI  - Functional morphology and patterns of blood flow in the heart of Python regius.
AB  - Brightness-modulated ultrasonography, continuous-wave Doppler, and pulsed-wave
      Doppler-echocardiography were used to analyze the functional morphology of the
      undisturbed heart of ball pythons. In particular, the action of the muscular
      ridge and the atrio-ventricular valves are key features to understand how
      patterns of blood flow emerge from structures directing blood into the various
      chambers of the heart. A step-by-step image analysis of echocardiographs shows
      that during ventricular diastole, the atrio-ventricular valves block the
      interventricular canals so that blood from the right atrium first fills the cavum
      venosum, and blood from the left atrium fills the cavum arteriosum. During
      diastole, blood from the cavum venosum crosses the muscular ridge into the cavum
      pulmonale. During middle to late systole the muscular ridge closes, thus
      prohibiting further blood flow into the cavum pulmonale. At the same time, the
      atrio-ventricular valves open the interventricular canal and allow blood from the
      cavum arteriosum to flow into the cavum venosum. In the late phase of ventricular
      systole, all blood from the cavum pulmonale is pressed into the pulmonary trunk;
      all blood from the cavum venosum is pressed into both aortas. Quantitative
      measures of blood flow volume showed that resting snakes bypass the pulmonary
      circulation and shunt about twice the blood volume into the systemic circulation
      as into the pulmonary circulation. When digesting, the oxygen demand of snakes
      increased tremendously. This is associated with shunting more blood into the
      pulmonary circulation. The results of this study allow the presentation of a
      detailed functional model of the python heart. They are also the basis for a
      functional hypothesis of how shunting is achieved. Further, it was shown that
      shunting is an active regulation process in response to changing demands of the
      organism (here, oxygen demand). Finally, the results of this study support
      earlier reports about a dual pressure circulation in Python regius.

PMID- 19097162
TI  - Are inflammatory bowel disease (IBD) and pouchitis a reactive enteropathy to
      group D streptococci (Enterococci)?

PMID- 19097163
TI  - Muenke syndrome with osteochondroma.

PMID- 19097164
TI  - White-matter lesions along the cholinergic tracts are related to cortical sources
      of EEG rhythms in amnesic mild cognitive impairment.
AB  - Does impairment of cholinergic systems represent an important factor in the
      development of amnesic mild cognitive impairment (aMCI), as a preclinical stage
      of Alzheimer's disease (AD)? Here we tested the hypothesis that
      electroencephalographic (EEG) rhythms, known to be modulated by the cholinergic
      system, may be particularly affected in aMCI patients with lesions along the
      cholinergic white-matter tracts. Eyes-closed resting EEG data were recorded in 28
      healthy elderly (Nold) and 57 aMCI patients. Lesions along the cholinergic white
      matter tracts were detected with fluid-attenuated inversion recovery sequences on
      magnetic resonance imaging. The estimation of the cholinergic lesion was
      performed with a validated semi-automatic algorithm pipeline after registration
      to a stereotactic template, image integration with stereotactic masks of the
      cholinergic tracts, and normalization to intracranial volume. The aMCI patients
      were divided into two groups of high (MCI Ch+; N = 29; MMSE = 26.2) and low
      cholinergic damage (MCI Ch-; N = 28; MMSE = 26.6). EEG rhythms of interest were
      delta (2-4 Hz), theta (4-8 Hz), alpha 1 (8-10.5 Hz), alpha 2 (10.5-13 Hz), beta 1
      (13-20 Hz), and beta 2 (20-30 Hz). Cortical EEG generators were estimated by
      LORETA software. As main results, (i) power of occipital, parietal, temporal, and
      limbic alpha 1 sources was maximum in Nold, intermediate in MCI Ch-, and low in
      MCI Ch+ patients; (ii) the same trend was true in theta sources. These results
      are consistent with the hypothesis that damage to the cholinergic system is
      associated with alterations of EEG sources in aMCI subjects.

PMID- 19097165
TI  - Amelogenin in cranio-facial development: the tooth as a model to study the role
      of amelogenin during embryogenesis.
AB  - The amelogenins comprise 90% of the developing extracellular enamel matrix
      proteins and play a major role in the biomineralization and structural
      organization of enamel. Amelogenins were also detected, in smaller amounts, in
      postnatal calcifying mesenchymal tissues, and in several nonmineralizing tissues
      including brain. Low molecular mass amelogenin isoforms were suggested to have
      signaling activity; to produce ectopically chondrogenic and osteogenic-like
      tissue and to affect mouse tooth germ differentiation in vitro. Recently, some
      amelogenin isoforms were found to bind to the cell surface receptors; LAMP-1,
      LAMP-2 and CD63, and subsequently localize to the perinuclear region of the cell.
      The recombinant amelogenin protein (rHAM(+)) alone brought about regeneration of
      the tooth supporting tissues: cementum, periodontal ligament and alveolar bone,
      in the dog model, through recruitment of progenitor cells and mesenchymal stem
      cells. We show that amelogenin is expressed in various tissues of the developing
      mouse embryonic cranio-facial complex such as brain, eye, ganglia, peripheral
      nerve trunks, cartilage and bone, and is already expressed at E10.5 in the brain
      and eye, long before the initiation of tooth formation. Amelogenin protein
      expression was detected in the tooth germ (dental lamina) already at E13.5, much
      earlier than previously reported (E19). Application of amelogenin (rHAM(+)) beads
      together with DiI, on E13.5 and E14.5 embryonic mandibular mesenchyme and on
      embryonic tooth germ, revealed recruitment of mesenchymal cells. The present
      results indicate that amelogenin has an important role in many tissues of the
      cranio-facial complex during mouse embryonic development and differentiation, and
      might be a multifunctional protein.

PMID- 19097166
TI  - Odontoblast: a mechano-sensory cell.
AB  - Odontoblasts are organized as a single layer of specialized cells responsible for
      dentine formation and presumably for playing a role in tooth pain transmission.
      Each cell has an extension running into a dentinal tubule and bathing in the
      dentinal fluid. A dense network of sensory unmyelinated nerve fibers surrounds
      the cell bodies and processes. Thus, dentinal tubules subjected to external
      stimuli causing dentinal fluid movements and odontoblasts/nerve complex response
      may represent a unique mechano-sensory system giving to dentine-forming cells a
      pivotal role in signal transduction. Mediators of mechano-transduction identified
      in odontoblast include mechano-sensitive ion channels (high conductance calcium
      activated potassium channel--K(Ca)--and a 2P domain potassium channel--TREK-1)
      and primary cilium. In many tissues, the latter is essential for microenvironment
      sensing but its role in the control of odontoblast behavior remains to be
      elucidated. Recent evidence for excitable properties and the concentration of key
      channels to the terminal web suggest that odontoblasts may operate as sensor
      cells.

PMID- 19097169
TI  - Standardization in microbial cytometry.

PMID- 19097168
TI  - Molecular screening of all colorectal tumors diagnosed before age 50 years
      followed by genetic testing efficiently identifies Lynch syndrome cases.

PMID- 19097170
TI  - A membrane-bound FRET-based caspase sensor for detection of apoptosis using
      fluorescence lifetime and total internal reflection microscopy.
AB  - A caspase sensor based on Forster resonance energy transfer between fluorescent
      proteins is reported. Enhanced cyan fluorescent protein anchored to the inner
      leaflet of the plasma membrane of living cells is optically excited by an
      evanescent electromagnetic field and transfers its excitation energy via a spacer
      (DEVD) to an enhanced yellow fluorescent protein. Upon apoptosis, DEVD is cleaved
      and energy transfer is disrupted, as proven by pronounced changes in fluorescence
      spectra and decay times. Fluorescence spectroscopy and lifetime imaging (FLIM) is
      combined with total internal reflection fluorescence microscopy (TIRFM) for
      selective detection of this membrane-bound caspase sensor. Fluorophores of the
      cytoplasm are thus excluded, and the signal-to-background ratio is increased
      considerably. In comparison with conventional or laser scanning microscopy, this
      permits long-term observation of apoptosis in live cell cultures using very low
      absorption and avoiding light-induced damages of the samples.

PMID- 19097171
TI  - Role-reversal of gender-associated mitochondrial DNA affects mitochondrial
      function in Mytilus edulis (Bivalvia: Mytilidae).
AB  - Mussel species of the genus Mytilus possess an unusual system of mitochondrial
      DNA (mtDNA) transmission termed doubly uniparental inheritance. They are
      characterized by the presence of two highly divergent gender-associated mtDNA
      genomes (often with>20 and>10% divergences in DNA and amino acid sequences,
      respectively) that are inherited either maternally (F mtDNA) or paternally (M
      mtDNA). Females are typically homoplasmic for the F mtDNA and males are
      heteroplasmic with the F mtDNA being most common in all tissues except the gonad
      that is dominated by the M mtDNA. Collectively, males are polymorphic for two
      classes of M mtDNAs known as the "standard male" and "recently masculinized" M
      types (SM and RM, respectively). The coding portions of the RM mtDNA genome
      differ from the SM mtDNA by as much as the maternally inherited F mtDNA genome
      differs from the SM type. Because the SM and RM types exhibit considerable amino
      acid sequence divergence, we hypothesized that these differences could affect
      mitochondrial respiratory chain complex enzyme activities. To test this
      hypothesis, the activity of the major mitochondrial respiratory chain complexes
      (complexes II, I+III and IV) as well as the activity of citrate synthase were
      measured on gonad samples from males containing either the SM or RM mtDNA. Our
      data demonstrate that the mitochondrial subunits encoded by the RM mtDNA are
      associated with higher enzymatic activities than the gene products of the SM
      mtDNA.

PMID- 19097172
TI  - Controlled light exposure microscopy reveals dynamic telomere microterritories
      throughout the cell cycle.
AB  - Telomeres are complex end structures that confer functional integrity and
      positional stability to human chromosomes. Despite their critical importance,
      there is no clear view on telomere organization in cycling human cells and their
      dynamic behavior throughout the cell cycle. We investigated spatiotemporal
      organization of telomeres in living human ECV-304 cells stably expressing
      telomere binding proteins TRF1 and TRF2 fused to mCitrine using four dimensional
      microscopy. We thereby made use of controlled light exposure microscopy (CLEM), a
      novel technology that strongly reduces photodamage by limiting excitation in
      parts of the image where full exposure is not needed. We found that telomeres
      share small territories where they dynamically associate. These territories are
      preferentially positioned at the interface of chromatin domains. TRF1 and TRF2
      are abundantly present in these territories but not firmly bound. At the onset of
      mitosis, the bulk of TRF protein dissociates from telomere regions, territories
      disintegrate and individual telomeres become faintly visible. The combination of
      stable cell lines, CLEM and cytometry proved essential in providing novel
      insights in compartment-based nuclear organization and may serve as a model
      approach for investigating telomere-driven genome-instability and studying long
      term nuclear dynamics.

PMID- 19097174
TI  - Clinical significance of Gata-1, Gata-2, EKLF, and c-MPL expression in acute
      myeloid leukemia.
AB  - The aim of this study was to evaluate the biological correlation and prognostic
      impact of Gata-1, Gata-2, EKLF, and c-MPL transcript level in a group of 41 acute
      myeloid leukemia (AML) patients. Gata-1 overexpression was related to advanced
      age and a low percentage of bone marrow blasts and was associated with the
      expression of CD34 antigen and lymphoid T markers. The negative impact of Gata-1
      expression on the probability of achieving complete remission has been confirmed.
      Gata-2 overexpression was associated with a low percentage of blasts in BM and
      males. Expression of c-MPL was associated with CD34+ AML and M2 FAB AML subtype.
      A higher expression of EKLF was found in secondary AML versus primary AML.
      Nevertheless, patients expressing EKLF had a longer overall survival and event
      free survival than those patients that did not express EKLF. Our study has
      identified expression of EKLF as a factor with a favorable impact on prognosis in
      AML.

PMID- 19097173
TI  - Catastrophic multiple organ ischemia due to an anti-Pr cold agglutinin developing
      in a patient with mixed cryoglobulinemia after treatment with rituximab.
AB  - Cold agglutinin disease occurring with cryoglobulinemia is a rare occurrence.
      Here, we report a patient with mixed cryoglobulinemia that was treated with
      rituximab and, after response, developed an anti-Pr cold agglutinin that
      manifested with hemolysis and microvascular occlusion causing mesenteric ischemia
      and cerebral infarction. Unlike previous reports of patients with
      cryoglobulinemia and cold agglutinin disease, our patient did not have a
      detectable cryoprecipitate when his cold agglutinin manifested.

PMID- 19097175
TI  - Replacement of dopaminergic medication with subthalamic nucleus stimulation in
      Parkinson's disease: long-term observation.
AB  - Stimulation of the subthalamic nucleus (STN) is an effective treatment for
      advanced Parkinson's disease (PD), but the medication requirements after implant
      are poorly known. We performed a long-term prospective evaluation of 20 patients
      maintained at stable dopaminergic therapy for 5 years after bilateral STN
      implants, who were evaluated 6 months, 1 year, 3 years, and 5 years after
      surgery. We measured, during the entire observation period, the effect of deep
      brain stimulation on motor and functional outcome measures, the levodopa
      equivalent daily dose and the total electrical energy delivered. At 5 years, the
      UPDRS motor score had improved by 54.2% and levodopa equivalent dose was reduced
      by 61.9%, compared with preimplant. Dopaminergic medication remained stable
      during the observation period, but energy was progressively increased over time.
      Rest tremor, rigidity, gait, lower and upper limb akinesia, and total axial score
      were improved in decreasing order. Postural stability and speech improved
      transiently, whereas on-period freezing of gait, motor fluctuations and
      dyskinesias recovered durably. Functional measures did not show improvement in
      autonomy and daily living activities after STN implant. Chronic STN stimulation
      allows to replace for dopaminergic medications in the long-term at the expense of
      an increase of the total energy delivered. This is associated with marked
      improvement of motor features without a matching benefit in functional measures.

PMID- 19097176
TI  - Genetic association study of the P-type ATPase ATP13A2 in late-onset Parkinson's
      disease.
AB  - A role of ATP13A2 in early-onset Parkinsonism (EOP) has been proposed.
      Conversely, the contribution of this ATPase to late-onset Parkinson's disease
      (PD) remains unexplored. We therefore conducted a case-control association study
      in this age-of-onset group with PD. The initial sample was of German origin and
      consisted of 220 patients with late-onset PD (mean age of onset 60.1 years) and
      232 age-matched unrelated controls. Five single nucleotide polymorphisms (SNPs)
      covering ATP13A2 and its common haplotypes were genotyped. The overall
      association results in this sample were negative. Interestingly, gender
      stratification gave a positive result for SNP rs11203280 (P(UNC) = 0.016) in men.
      This result could not be reproduced in a replication sample of German and Serbian
      origin composed of 161 patients with late-onset PD (mean age of onset 51.7 years)
      and 150 age- and ethnic-matched controls. In conclusion, we found no consistent
      evidence for an association between ATP13A2 and late-onset PD.

PMID- 19097177
TI  - The impact of an intense religious experience on motor symptoms in Huntington's
      disease.

PMID- 19097178
TI  - Rasch analysis of the hospital anxiety and depression scale in Parkinson's
      disease.
AB  - The hospital anxiety and depression scale (HADS) is commonly used to assess mood
      in Parkinson's disease (PD) patients. Very few studies analyze the scale from the
      standpoint of item response theory. This article sought to analyze how the HADS
      fits the Rasch model in PD. The HADS was administered to 387 PD patients. Three
      sets of Rasch analyses were performed for the HADS total score, and anxiety and
      depression subscales (HADS-T, -A, and -D, respectively). Although the HADS-T and
      HADS-A displayed a good fit, with little threshold disordering and no
      differential item functioning, the HADS-D failed to fit the model. The person
      separation index, a reliability measure, was 0.87 (HADS-T) and 0.80 (HADS-A).
      Both HADS-T and HADS-A showed unidimensionality. Our results supported the use of
      HADS-T as a measure of psychological distress in PD patients. Moreover, the HADS
      A was also an adequate anxiety measure. Further research is required to address
      the use of HADS-D in PD.

PMID- 19097179
TI  - Factors contributing to the development of restless legs syndrome in patients
      with Parkinson disease.
AB  - Although restless legs syndrome (RLS) commonly accompanies Parkinson disease
      (PD), the mechanism of RLS development in PD is still unclear. We investigated
      the prevalence of RLS in Korean patients with PD, and the possible contributing
      factors to the development of RLS in those patients. Four hundred forty-seven
      consecutive patients with PD were interviewed and examined. Among them, 73
      patients (16.3%) were diagnosed with RLS. PD patients with RLS had a longer
      duration of PD symptoms, more severe PD disability, a greater degree of cognitive
      decline, and a longer duration of antiparkinson therapy than those without RLS.
      Multivariate logistic regression analysis revealed that the duration of
      antiparkinson therapy was the most significant factor contributing to the
      development of RLS in patients with PD. The present results support a higher
      prevalence of RLS in patients with PD and suggest that long-term antiparkinson
      therapy, rather than PD itself, may contribute to the development of RLS.

PMID- 19097181
TI  - Health-related quality of life in Huntington's disease: Which factors matter
      most?
AB  - The aim of this article was to determine which aspects of Huntington's disease
      (HD) are most important with regard to the health-related quality of life (HrQOL)
      of patients with this neurodegenerative disease. Seventy patients with HD
      participated in the study. Assessment comprised the Unified Huntington's Disease
      Rating Scale (UHDRS) motor, cognitive and functional capacity sections, and the
      Beck Depression inventory. Mental and physical HrQOL were assessed using summary
      scores of the SF-36. Multiple regression analyses showed that functional capacity
      and depressive mood were significantly associated with HrQOL, in that greater
      impairments in HrQOL were associated with higher levels of depressive mood and
      lower functional capacity. Motor symptoms and cognitive function were not found
      to be as closely linked with HrQOL. Therefore, it can be concluded that,
      depressive mood and greater functional incapacity are key factors in HrQOL for
      people with HD, and further longitudinal investigation will be useful to
      determine their utility as specific targets in intervention studies aimed at
      improving patient HrQOL, or whether other mediating variables. As these two
      factors had a similar association with the mental and physical summary scores of
      the SF-36, this generic HrQOL measure did not adequately capture and distinguish
      the true mental and physical health-related HrQOL in HD.

PMID- 19097182
TI  - Hemidystonia-hemiatrophy syndrome.
AB  - To define the clinical and radiological features of patients with the combination
      of hemidystonia (HD) and hemiatrophy (HA), the HD-HA syndrome. HD is a very
      disabling neurological condition that is rarely associated with HA of the
      affected body part, similar to the hemiparkinsonism-hemiatrophy syndrome. METHOD:
      We reviewed the medical records of 26 patients with the HD-HA syndrome and the
      data was entered into a database and analyzed. Video recordings as well as
      imaging studies were also reviewed. Twenty six patients (14 female) with a mean
      age at onset of HD at 14.9 years (1-46 years) were followed for a mean of 3.4
      years. Fourteen (53%) had HD and HA on the left side and 23 (88%) had hemiparesis
      preceding the onset of HD. The mean latency from the onset of hemiparesis to the
      onset of HD was 14.7 years (2 weeks-46 years). All patients with hemiparesis had
      marked improvement in their weakness prior to the onset of HD. Common causes
      leading to hemiparesis and subsequent HD were birth or perinatal complications (N
      = 13) and stroke (N = 10). Seven patients (26%) had associated seizures. Twenty
      two patients (85%) had abnormal brain MRI: eight had lesions directly involving
      the basal ganglia and nine had cerebral hemiatrophy or non specific diffuse
      atrophy. Sixteen patients received botulinum toxin injections and responded well
      to treatment. HD-HA is usually associated with static encephalopathy originating
      at very young age, but the syndrome may also represent delayed sequelae of a
      stroke or brain injury.

PMID- 19097183
TI  - Thalamic stimulation restores defective cerebellocortical inhibition in multiple
      sclerosis tremor.

PMID- 19097184
TI  - Transcriptional dynamics of endodermal organ formation.
AB  - Although endodermal organs including the liver, pancreas, and intestine are of
      significant therapeutic interest, the mechanism by which the endoderm is divided
      into organ domains during embryogenesis is not well understood. To better
      understand this process, global gene expression profiling was performed on early
      endodermal organ domains. This global analysis was followed up by dynamic
      immunofluorescence analysis of key transcription factors, uncovering novel
      expression patterns as well as cell surface proteins that allow prospective
      isolation of specific endodermal organ domains. Additionally, a repressive
      interaction between Cdx2 and Sox2 was found to occur at the prospective stomach
      intestine border, with the hepatic and pancreatic domains forming at this
      boundary, and Hlxb9 was revealed to have graded expression along the dorsal
      ventral axis. These results contribute to understanding the mechanism of
      endodermal organogenesis and should assist efforts to replicate this process
      using pluripotent stem cells.

PMID- 19097185
TI  - Identification and characterization of two zebrafish nectin-1 genes that are
      differentially expressed in the developing eye and brain.
AB  - Nectins are cell adhesion molecules of the immunoglobulin type that play
      important roles in the development of the nervous system. We have characterized
      two paralogous zebrafish nectin-1 genes, nectin-1a and nectin-1b, that differ in
      expression. Nectin-1a expression is first found in the anterior neural keel and
      later in the optic cup. In the retina, nectin-1a appears in the outer part and
      extends inwards, while nectin-1b starts in the inner part and spreads outwards.
      Only nectin-1a was detected in the cornea, the lens, and in the region of
      photoreceptor cell differentiation in the retina. Both genes were expressed in
      ganglion cells and inner nuclear neurons. In the brain, nectin-1a was restricted
      to the epiphysis and a cluster of cells in the posterior hindbrain, whereas
      nectin-1b was found in several brain areas. Zebrafish may, therefore, be a useful
      model for identifying different functions of nectin-1 in the developing eye and
      nervous system.

PMID- 19097186
TI  - Nasal embryonic LHRH factor plays a role in the developmental migration and
      projection of gonadotropin-releasing hormone 3 neurons in zebrafish.
AB  - The initiation of puberty and the functioning of the reproductive system depend
      on proper development of the hypophysiotropic gonadotropin-releasing hormone
      (GnRH) system. One critical step in this process is the embryonic migration of
      GnRH neurons from the olfactory area to the hypothalamus. Using a transgenic
      zebrafish model, Tg(gnrh3:EGFP), in which GnRH3 neurons and axons are
      fluorescently labeled, we investigated whether zebrafish NELF is essential for
      the development of GnRH3 neurons. The zebrafish nelf cDNA was cloned and
      characterized. During embryonic development, nelf is expressed in GnRH3 neurons
      and in target sites of GnRH3 projections and perikarya, before the initiation of
      their migration. Nelf knockdown resulted in a disruption of the GnRH3 system
      which included absence or misguiding of GnRH3 axonal outgrowth and incorrect or
      arrested migration of GnRH3 perikarya. These results suggest that Nelf is an
      important factor in the developmental migration and projection of GnRH3 neurons
      in zebrafish.

PMID- 19097187
TI  - Many ribosomal protein mutations are associated with growth impairment and tumor
      predisposition in zebrafish.
AB  - We have characterized 28 zebrafish lines with heterozygous mutations in ribosomal
      protein (rp) genes, and found that 17 of these are prone to develop zebrafish
      malignant peripheral nerve sheath tumors (zMPNST). Heterozygotes from the vast
      majority of tumor-prone rp lines were found to be growth-impaired, though not all
      growth-impaired rp lines were tumor-prone. Significantly, however, the rp lines
      with the greatest incidence of zMPNSTs all displayed a growth impairment.
      Furthermore, heterozygous cells from one tumor-prone rp line were out-competed by
      wild-type cells in chimeric embryos. The growth impairment resulting from
      heterozygosity for many rp genes suggests that a global defect in protein
      translation exists in these lines, raising the possibility that a translation
      defect that precedes tumor development is predictive of tumorigenesis.

PMID- 19097188
TI  - RNA profiling of FAC-sorted neurons from the developing zebrafish spinal cord.
AB  - In this report, we describe a successful protocol for isolating and expression
      profiling live fluorescent-protein-labelled neurons from zebrafish embryos. As a
      proof-of-principle for this method, we FAC-sorted and RNA-profiled GFP-labelled
      spinal CiA interneurons and compared the expression profile of these cells to
      those of post-mitotic spinal neurons in general and to all trunk cells. We show
      that RNA of sufficient quality and quantity to uncover both expected and novel
      transcription profiles via Affymetrix microarray analysis can be extracted from
      5,700 to 20,000 FAC-sorted cells. As part of this study, we also further confirm
      the genetic homology of mammalian and zebrafish V1 interneurons, by demonstrating
      that zebrafish V1 cells (CiAs) express genes that encode for the transcription
      factors Lhx1a and Lhx5. This protocol for dissociating, sorting and RNA-profiling
      neurons from organogenesis-stage zebrafish embryos should also be applicable to
      other developing organs and tissues and potentially other model organisms.

PMID- 19097189
TI  - Improved asymmetry of gait in Parkinson's disease with DBS: gait and postural
      instability in Parkinson's disease treated with bilateral deep brain stimulation
      in the subthalamic nucleus.
AB  - Postural instability is a sign of progression of Parkinson's disease (PD) and
      often resistant to levodopa treatment. To explore the effect of bilateral deep
      brain stimulation (DBS) of the subthalamic nucleus (STN) on postural stability
      and gait, full body gait analyses were performed without medication, OFF and ON
      DBS in eight PD patients and 12 healthy age-matched controls. DBS setting was
      changed at least 3 hours before gait analysis. To describe asymmetry most and
      least affected sides (MAS and LAS) were rated with the Unified Parkinson's
      Disease Rating Scale, motor part and quantitative gait analysis with the Vicon
      612 gait analysis system. Stride length and gait velocity but not cadence
      improved ON DBS. The distances between the heel markers and center of mass (COM)
      were asymmetric and reduced OFF DBS. STN DBS increased the distances
      significantly and reduced asymmetry. The improvement in heel to COM distance was
      larger on the MAS compared with the LAS. OFF DBS knee momentum asymmetry was
      inversed so that LAS was more impaired than MAS. ON DBS asymmetry improved. PD
      patients OFF DBS place the heel too close to COM. The most affected body side has
      the most impaired swing and the result is a smaller knee moment on the opposite
      and least affected body side and an asymmetric gait pattern with disturbed
      balance OFF STN DBS. The asymmetry OFF DBS improved ON DBS. We suggest that DBS
      facilitates symmetric gait and thereby improves balance during gait.

PMID- 19097190
TI  - The unfulfilled/DHR51 gene of Drosophila melanogaster modulates wing expansion
      and fertility.
AB  - This is the first functional analysis in Drosophila of unfulfilled (unf; DHR51),
      the NR2E3 nuclear receptor superfamily ortholog of C. elegans fax-1 and human
      PNR. Both fax-1 and PNR mutations disrupt developmental events in a limited
      number of neurons, resulting in behavioral or sensory deficits. An analysis of
      two independent unf alleles revealed that unf mutants are characterized by one of
      two phenotypes. A proportion of the mutants eclosed but failed to expand their
      wings and were poorly coordinated. The remainder completed wing expansion but
      displayed severely compromised fertility. Consistent with the restricted neural
      expression of fax-1 and PNR, unf expression was detected in situ only in mushroom
      body neurons and a small number of other cells of the central nervous system
      (CNS). These data support the hypothesis that the wing expansion failure and the
      compromised fertility of unf mutants are the result of underlying neural defects.

PMID- 19097191
TI  - Podoplanin deficient mice show a RhoA-related hypoplasia of the sinus venosus
      myocardium including the sinoatrial node.
AB  - We investigated the role of podoplanin in development of the sinus venosus
      myocardium comprising the sinoatrial node, dorsal atrial wall, and primary atrial
      septum as well as the myocardium of the cardinal and pulmonary veins. We analyzed
      podoplanin wild-type and knockout mouse embryos between embryonic day 9.5-15.5
      using immunohistochemical marker podoplanin; sinoatrial-node marker HCN4;
      myocardial markers MLC-2a, Nkx2.5, as well as Cx43; coelomic marker WT-1; and
      epithelial-to-mesenchymal transformation markers E-cadherin and RhoA. Three
      dimensional reconstructions were made and myocardial morphometry was performed.
      Podoplanin mutants showed hypoplasia of the sinoatrial node, primary atrial
      septum, and dorsal atrial wall. Myocardium lining the wall of the cardinal and
      pulmonary veins was thin and perforated. Impaired myocardial formation is
      correlated with abnormal epithelial-to-mesenchymal transformation of the coelomic
      epithelium due to up-regulated E-cadherin and down-regulated RhoA, which are
      controlled by podoplanin. Our results demonstrate an important role for
      podoplanin in development of sinus venosus myocardium.

PMID- 19097192
TI  - Cloning and expression analysis of the anterior parahox genes, Gsh1 and Gsh2 from
      Xenopus tropicalis.
AB  - Gsx class proteins are members of the ParaHox homeodomain transcription factor
      family with conserved roles in specification and patterning of the nervous
      system. We report the cloning of two Gsx genes, Gsh1 and Gsh2, from the frog
      Xenopus tropicalis. We demonstrate the existence of a single, intact Xenopus
      ParaHox cluster, containing Gsh1, Pdx, and Cdx2, plus three degenerate clusters
      containing Gsh2, Cdx1, and Cdx4. Anterior expression boundaries of genes from the
      intact ParaHox cluster are co-linear with respect to their genomic organization.
      We show that Gsh1 and Gsh2 exhibit complex, overlapping patterns of expression
      within the anterior nervous system from open neural plate stages. We also find
      that expression of Gsh2, Nkx6, and Msx1 across the medio-lateral axis of the
      amphibian neural plate is strikingly similar to that of related genes in the
      Drosophila neuroectoderm. These findings provide further evidence for a conserved
      pathway regulating dorso-ventral patterning in the Bilateria.

PMID- 19097193
TI  - Anatomy, physiology, and pathophysiology of the pedunculopontine nucleus.
AB  - The pedunculopontine nucleus is composed of cholinergic and non-cholinergic
      neurones and is located in the caudal pontomesencephalic tegmentum. Evidence
      suggests that the nucleus plays a role in the production and control of movement.
      The nucleus has dense interconnections with the basal ganglia, as well as with
      other areas of the brain associated with motor control. Electrical stimulation of
      the pedunculopontine nucleus in the decerebrate cat or rat produces organized
      locomotor movements. Physiological studies show that the pedunculopontine nucleus
      modulates its activity in response to locomotion, as well as voluntary arm and
      eye movements. Degeneration of the pedunculopontine nucleus is seen in post
      mortem brains in humans with Parkinson's disease and Parkinsonian syndromes. In
      animal models of Parkinson's disease, metabolic changes are seen in the
      pedunculopontine nucleus, and chemical inhibition or mechanical disruption of the
      nucleus can produce an akinetic state in animals and man. In this paper we review
      the literature in support of the suggestion that some of the symptoms of
      Parkinson's disease are caused by dysfunction of the pedunculopontine nucleus. In
      accordance with this view, direct stimulation of the nucleus can ameliorate some
      symptoms of the disease, as demonstrated in both experimental animals and man.

PMID- 19097194
TI  - Short limbs, cleft palate, and delayed formation of flat proliferative
      chondrocytes in mice with targeted disruption of a putative protein kinase gene,
      Pkdcc (AW548124).
AB  - During long bone development, round proliferative chondrocytes (RPCs)
      differentiate into flat proliferative chondrocytes (FPCs), and then into
      hypertrophic chondrocytes (HCs). FPCs and HCs support longitudinal bone growth.
      Here we show that a putative protein kinase gene, Pkdcc (AW548124), is required
      for longitudinal bone growth. We originally found Pkdcc expressed in the head
      organizer, but it is also expressed throughout embryogenesis and in various adult
      tissues. Pkdcc-/- embryos had no head organizer-related defects, but showed
      various morphological abnormalities at birth, including short limbs, cleft
      palate, sternal dysraphia, and shortened intestine. In the long bones of the
      limbs, only the mineralized regions were shortened, and the cartilage length was
      normal. In the humerus, Pkdcc was strongly expressed in the early FPCs, and FPC
      and HC formation was delayed in Pkdcc-/- mutants. Together, these data indicate
      that Pkdcc encodes a protein kinase that is required for the appropriate timing
      of FPC differentiation.

PMID- 19097196
TI  - Morphology of the heart.

PMID- 19097195
TI  - Muscular dystrophy candidate gene FRG1 is critical for muscle development.
AB  - The leading candidate gene responsible for facioscapulohumeral muscular dystrophy
      (FSHD) is FRG1 (FSHD region gene 1). However, the correlation of altered FRG1
      expression levels with disease pathology has remained controversial and the
      precise function of FRG1 is unknown. Here, we carried out a detailed analysis of
      the normal expression patterns and effects of FRG1 misexpression during
      vertebrate embryonic development using Xenopus laevis. We show that frg1 is
      expressed in and essential for the development of the tadpole musculature. FRG1
      morpholino injection disrupted myotome organization and led to inhibited myotome
      growth, while elevated FRG1 led to abnormal epaxial and hypaxial muscle
      formation. Thus, maintenance of normal FRG1 levels is critical for proper muscle
      development, supportive of FSHD disease models whereby misregulation of FRG1
      plays a causal role underlying the pathology exhibited in FSHD patients.
      Developmental Dynamics 238:1502-1512, 2009. (c) 2008 Wiley-Liss, Inc.

PMID- 19097197
TI  - MR imaging during endovascular procedures: an evaluation of the potential for
      catheter heating.
AB  - MRI in catheterized patients is considered unsafe due to the potential for focal
      heating. This concern arises from the continuous metallic braid that is
      incorporated into catheters to provide their desired physical properties. The
      potential for catheter heating during MR scanning was assessed in an in vitro
      model simulating a patient undergoing a neurovascular procedure in which MR scans
      of the brain will be performed. Heating adjacent to endovascular devices was
      assessed with fluoroptic temperature probes in a polyacrylamide gel. The effect
      of variable immersion lengths, lateral and longitudinal offsets, position along
      the endovascular device, physical MR system, and specific absorption rate (SAR)
      level were studied to determine their effect on catheter heating. A rapid
      temperature rise was evident next to endovascular devices during MR scanning and
      varied moderately with immersed length, position within the bore, measurement
      point on the device, and MR system used. Peak heating rates were less than 1
      degree C/min with maximal SAR exposure and anatomically realistic geometries.
      Heating scaled linearly with SAR and SAR values below 0.2 W/kg produced
      negligible heating near catheters. For the evaluated application, substantial SAR
      restrictions, coupled with limited imaging durations, are proposed as sufficient
      to permit MRI without concern for thermal injury.

PMID- 19097198
TI  - Phospholipid composition of postmortem schizophrenic brain by 31P NMR
      spectroscopy.
AB  - Cell membrane abnormalities due to changes in phospholipid (PL) composition and
      metabolism have been implicated in schizophrenia pathogenesis. That work has
      generally assessed membrane phospholipids from nonneural tissues such as
      erythrocytes and platelets. High-resolution (31)P NMR spectroscopy was used to
      characterize PLs of gray matter in postmortem brain for 20 schizophrenics, 20
      controls, and 7 patients with other mental illnesses (psychiatric controls).
      Tissues from frontal, temporal, and occipital cortices were extracted with hexane
      isopropanol, and (31)P NMR spectra were obtained in an organic-solvent system to
      resolve the major PL classes (based on headgroups) and subclasses (based on
      linkage at the sn - 1 position). Surprisingly, repeated-measures multivariate
      analysis of variance revealed no overall differences among the groups. There were
      no significant differences (P < .05) among the three groups for any individual PL
      subclass, including lysophospholipids. The sum of all phosphatidylethanolamine
      headgroups was significantly lower for schizophrenics than for controls or
      psychiatric controls in the frontal cortex. The present results are minimally
      correlated with previous results for aqueous PL metabolites on these same
      samples. The metabolite changes measured by in vivo (31)P MRS in schizophrenia do
      not appear to reflect PL concentration changes. The present results offer very
      little support for the phospholipid hypothesis of schizophrenia.

PMID- 19097199
TI  - Calibration of RF transmitter voltages for hyperpolarized gas MRI.
AB  - MRI with hyperpolarized gases, (3)He, (129)Xe, (13)C, and others, has the
      potential to become an important diagnostic technique for clinical imaging. Due
      to the nonreversible loss of magnetization in hyperpolarized gas imaging, the
      choice of the flip angle is a major factor that influences the signal intensity,
      and hence, the signal-to-noise ratio. Conventional automated radiofrequency (RF)
      calibration procedures for (1)H imaging are not suitable for hyperpolarized gas
      imaging. Herein, we have demonstrated a simple procedure for RF calibration for
      magnetic resonance imaging (MRI) with hyperpolarized gases that is easily
      adaptable to clinical settings. We have demonstrated that there exists a linear
      relationship between the RF transmitter voltages required to obtain the same
      nutation angle for protons (V(1H)) and hyperpolarized gas nuclei (V(3He)). For
      our (1)H and (3)He coils we found that V(3He) = 1.937 . V(1H) with correlation
      coefficient r(2) = 0.97. This calibration can be done as a one-time procedure
      during the routine quality assurance (QA) protocol. The proposed procedure was
      found to be extremely robust in routine scanning and provided an efficient method
      to achieve a desired flip angle, thus allowing optimum image quality.

PMID- 19097200
TI  - Spin-echo MRI using pi/2 and pi hyperbolic secant pulses.
AB  - Frequency-modulated (FM) pulses have practical advantages for spin-echo
      experiments, such as the ability to produce a broadband pi rotation, with an
      inhomogeneous radiofrequency (RF) field. However, such use leads to a nonlinear
      phase of the transverse magnetization, which is why FM pulses like the hyperbolic
      secant (HS) pulse are not commonly used for multislice spin-echo magnetic
      resonance imaging (MRI). Here, a general theory and methods are described for
      conventional spin-echo imaging using a pi HS pulse for refocusing. Phase profiles
      produced by the HS pulse are analytically described. The analysis is extended to
      yield the specific relationships between pulse parameters and gradients, which
      must be satisfied to compensate the nonlinear phase variation produced with a
      spin-echo sequence composed of pi/2 and pi HS pulses (the pi/2 HS - pi HS
      sequence). The latter offers advantages for multislice spin-echo MRI, including
      excellent slice-selection and partial compensation for RF inhomogeneity.
      Furthermore, it can be implemented with a shorter echo time and lower power
      deposition than a previously described method using a pair of pi HS pulses.

PMID- 19097201
TI  - Turboprop IDEAL: a motion-resistant fat-water separation technique.
AB  - Suppression of the fat signal in MRI is very important for many clinical
      applications. Multi-point water-fat separation methods, such as IDEAL (Iterative
      Decomposition of water and fat with Echo Asymmetry and Least-squares estimation),
      can robustly separate water and fat signal, but inevitably increase scan time,
      making separated images more easily affected by patient motions. PROPELLER
      (Periodically Rotated Overlapping ParallEL Lines with Enhanced Reconstruction)
      and Turboprop techniques offer an effective approach to correct for motion
      artifacts. By combining these techniques together, we demonstrate that the new TP
      IDEAL method can provide reliable water-fat separation with robust motion
      correction. The Turboprop sequence was modified to acquire source images, and
      motion correction algorithms were adjusted to assure the registration between
      different echo images. Theoretical calculations were performed to predict the
      optimal shift and spacing of the gradient echoes. Phantom images were acquired,
      and results were compared with regular FSE-IDEAL. Both T1- and T2-weighted images
      of the human brain were used to demonstrate the effectiveness of motion
      correction. TP-IDEAL images were also acquired for pelvis, knee, and foot,
      showing great potential of this technique for general clinical applications.

PMID- 19097203
TI  - Cancer survivors need a plan.

PMID- 19097202
TI  - Long-range diffusion of hyperpolarized 3He in rats.
AB  - Based on a stimulated-echo technique, a method to construct an apparent diffusion
      coefficient (ADC) map of hyperpolarized (3)He in a long-range diffusion scale is
      presented with a phase-cycle alternative to remove all unwanted echoes. The
      approach was successfully applied to determine in vivo diffusion constants in rat
      lungs. The ADC values in healthy rats show a good agreement with reported values
      for diffusion times of approximately. These long diffusivity measurements may be
      sensitive to detect emphysema progression or tissue remodeling and thus have
      enormous potential for the diagnosis and tracking of disease progression and for
      drug evaluation.

PMID- 19097204
TI  - Quantitative magnetization transfer characteristics of the human cervical spinal
      cord in vivo: application to adrenomyeloneuropathy.
AB  - Magnetization transfer (MT) imaging has assessed myelin integrity in the brain
      and spinal cord; however, quantitative MT (qMT) has been confined to the brain or
      excised tissue. We characterized spinal cord tissue with qMT in vivo, and as a
      first application, qMT-derived metrics were examined in adults with the genetic
      disorder Adrenomyeloneuropathy (AMN). AMN is a progressive disease marked by
      demyelination of the white matter tracts of the cervical spinal cord, and a
      disease in which conventional MRI has been limited. MT data were acquired at 1.5
      Tesla using 10 radiofrequency offsets at one power in the cervical cord at C2 in
      6 healthy volunteers and 9 AMN patients. The data were fit to a two-pool MT model
      and the macromolecular fraction (M(ob)), macromolecular transverse relaxation
      time (T(2b)) and the rate of MT exchange (R) for lateral and dorsal column white
      matter and gray matter were calculated. M(ob) for healthy volunteers was: WM =
      13.9 +/- 2.3%, GM = 7.9 +/- 1.5%. In AMN, dorsal column M(ob) was significantly
      decreased (P < 0.03). T(2b) for volunteers was: 9 +/- 2 micros and the rate of MT
      exchange (R) was: WM = 56 +/- 11 Hz, GM = 67 +/- 12 Hz. Neither T(2b) nor R
      showed significant differences between healthy and diseased cords. Comparisons
      are made between qMT, and conventional MT acquisitions.

PMID- 19097205
TI  - Calculation of susceptibility through multiple orientation sampling (COSMOS): a
      method for conditioning the inverse problem from measured magnetic field map to
      susceptibility source image in MRI.
AB  - Magnetic susceptibility differs among tissues based on their contents of iron,
      calcium, contrast agent, and other molecular compositions. Susceptibility
      modifies the magnetic field detected in the MR signal phase. The determination of
      an arbitrary susceptibility distribution from the induced field shifts is a
      challenging, ill-posed inverse problem. A method called "calculation of
      susceptibility through multiple orientation sampling" (COSMOS) is proposed to
      stabilize this inverse problem. The field created by the susceptibility
      distribution is sampled at multiple orientations with respect to the polarization
      field, B(0), and the susceptibility map is reconstructed by weighted linear least
      squares to account for field noise and the signal void region. Numerical
      simulations and phantom and in vitro imaging validations demonstrated that COSMOS
      is a stable and precise approach to quantify a susceptibility distribution using
      MRI.

PMID- 19097206
TI  - Quantifying hepatic glycogen synthesis by direct and indirect pathways in rats
      under normal ad libitum feeding conditions.
AB  - Hepatic glycogen synthesis from intact hexose (direct pathway) relative to that
      from gluconeogenic precursors (indirect pathway) was quantified in ad libitum-fed
      rats. Following (2)H(2)O administration and overnight feeding, the livers were
      removed and glycogen (2)H-enrichment was measured by (2)H NMR. Six controls and
      six rats rendered hyperglycemic by streptozotocin (STZ; fasting blood glucose =
      385 +/- 31 mg/dl) were studied. The indirect pathway contribution, estimated as
      glycogen hydrogen 5 relative to hydrogen 2 enrichment, was 54% +/- 4% for control
      rats-similar to values from healthy, meal-fed humans. In STZ-treated rats, the
      indirect pathway contribution was significantly higher (68% +/- 4%, P < 0.05 vs.
      controls), similar to that of Type 1 diabetic (T1D) patients. In conclusion,
      sources of hepatic glycogen synthesis in rats during ad libitum nocturnal feeding
      were quantified by analysis of glycogen enrichment from (2)H(2)O. STZ caused
      alterations resembling the pathophysiology of hepatic glycogen synthesis in T1D
      patients.

PMID- 19097207
TI  - Orientation of lipid strands in the extracellular compartment of muscle: effect
      on quantitation of intramyocellular lipids.
AB  - Single-voxel (1)H NMR spectra from gastrocnemius and soleus muscle were acquired
      in healthy volunteers at 7T with the objective of measuring the concentration of
      intramyocellular lipid [IMCL] (note: throughout this article, square brackets
      indicate concentration). However, significant asymmetry in the resonance assigned
      to the methylene protons (-CH(2)-)(n) in extramyocellular lipids (EMCL)
      interfered with fitting the spectra. Since muscle fibers in these tissues are
      generally not parallel to B(0), the influence of variable orientation in strands
      of extracellular fat was examined using a mathematical model. Modest variation in
      orientation produced asymmetric lineshapes that were qualitatively similar to
      typical observations at 7T. Analysis of simulated spectra by fitting with a Voigt
      function overestimated [IMCL]/[EMCL] except when EMCL fibers were nearly parallel
      to B(0). Estimates of [IMCL]/[EMCL] were improved by including variations in
      fiber orientation in the lineshape analysis (fiber orientation modeling, or FOM).
      Calculated [IMCL] using FOM, 4.8 +/- 2.2 mmol/kg wet weight, was lower compared
      to most previous reports in soleus.

PMID- 19097208
TI  - The tensor distribution function.
AB  - Diffusion weighted magnetic resonance imaging is a powerful tool that can be
      employed to study white matter microstructure by examining the 3D displacement
      profile of water molecules in brain tissue. By applying diffusion-sensitized
      gradients along a minimum of six directions, second-order tensors (represented by
      three-by-three positive definite matrices) can be computed to model dominant
      diffusion processes. However, conventional DTI is not sufficient to resolve more
      complicated white matter configurations, e.g., crossing fiber tracts. Recently, a
      number of high-angular resolution schemes with more than six gradient directions
      have been employed to address this issue. In this article, we introduce the
      tensor distribution function (TDF), a probability function defined on the space
      of symmetric positive definite matrices. Using the calculus of variations, we
      solve the TDF that optimally describes the observed data. Here, fiber crossing is
      modeled as an ensemble of Gaussian diffusion processes with weights specified by
      the TDF. Once this optimal TDF is determined, the orientation distribution
      function (ODF) can easily be computed by analytic integration of the resulting
      displacement probability function. Moreover, a tensor orientation distribution
      function (TOD) may also be derived from the TDF, allowing for the estimation of
      principal fiber directions and their corresponding eigenvalues.

PMID- 19097209
TI  - Disparities in survival among women with invasive cervical cancer: a problem of
      access to care.
AB  - BACKGROUND: In this study, the authors sought to understand the effects of
      patient race, ethnicity, and socioeconomic status (SES) on outcomes for cervical
      cancer. METHOD: The Florida Cancer Data System and the Agency for Health Care
      Administration data sets (1998-2003) were merged and queried. Survival outcomes
      for patients with invasive cervical cancer were compared between different races,
      ethnicities, and community poverty levels. RESULTS: In total, 5367 patients with
      cervical cancers were identified. The overall median survival was 43 months.
      Significantly longer survival was observed for Caucasians (47.1 months vs 28.8
      months for African Americans [AA]; P<.001), Hispanics (52.8 months vs 41.6 months
      for non-Hispanics; P<.001), the insured (63 months vs 41.2 months for uninsured;
      P<.001), and patients from more affluent communities (53.3 months where <5% lived
      in poverty vs 36.9 months where >15% lived in poverty; P<.001). Surgery was
      associated with dramatically improved survival. AA women who were diagnosed with
      cervical cancer were significantly less likely to undergo surgical treatment with
      curative intent compared with Caucasian women (P<.001). However, on multivariate
      analysis, independent predictors of poorer outcomes were insurance status, tumor
      stage, tumor grade, and treatment. Neither race, nor ethnicity, nor SES was an
      independent predictor of poorer outcome. CONCLUSIONS: Race, ethnic, and SES
      disparities in cervical cancer survival were explained by late-stage presentation
      and under-treatment. Earlier diagnosis and greater access to surgery and other
      treatments would significantly improve the survival of women with cervical
      cancer.

PMID- 19097210
TI  - On the steady-state properties of actual flip angle imaging (AFI).
AB  - AFI (actual flip angle imaging) represents an interesting approach to map the
      B(1) transmit fields by measuring the spatial variations of the effective flip
      angle. However, the accuracy of the technique relies on the adequate spoiling of
      transverse magnetization. In the present work configuration theory was employed
      to develop a proper RF and gradient spoiling scheme for the AFI technique, making
      the sequence robust against off-resonance without the need of large spoiling
      gradients. Furthermore, numerical simulations were performed to predict the
      steady-state signals and, hence, the accuracy of the AFI technique as a function
      of the sequence and tissue parameters. It is shown that the spoiling properties
      of the sequence are mainly defined by the phase shift increment phi of the RF
      pulses and the diffusion sensitivity resulting from the unbalanced gradients of
      the sequence. Adequate spoiling may be achieved for a reasonable range of tissue
      parameters and flip angles for moderate spoiling gradients if a favorable value
      for phi is chosen. Phantom and in vivo head imaging experiments show an excellent
      agreement with the theoretical predictions, indicating that the proper operating
      range of the approach may be reliably predicted by the theory.

PMID- 19097211
TI  - Virtual coil concept for improved parallel MRI employing conjugate symmetric
      signals.
AB  - A new approach for utilizing conjugate k-space symmetry for improved parallel MRI
      performance is presented. By generating virtual coils containing conjugate
      symmetric k-space signals from actual coils, additional image- and coil-phase
      information can be incorporated into the reconstruction process for parallel
      acquisition techniques. In that way the reconstruction conditions are improved,
      resulting in less noise enhancement. In particular in combination with
      generalized autocalibrating partially parallel acquisitions (GRAPPA), the virtual
      coil concept represents a practical approach since no explicit spatial phase
      information is required. In addition, the influence of phase variations
      originating from the complex receiver coils as well as from the background is
      investigated. It is shown that there exist background phase distributions
      yielding an optimized pMRI reconstruction.

PMID- 19097212
TI  - Comparison of normal tissue R1 and R*2 modulation by oxygen and carbogen.
AB  - Magnetic resonance imaging has shown promise for evaluating tissue oxygenation.
      In this study differences in the tissue longitudinal relaxation rate (R(1)) and
      effective transverse relaxation rate (R(*)(2)), induced by inhalation of pure
      oxygen and carbogen, were evaluated in 10 healthy subjects. Significant
      reductions in R(1) were demonstrated following both oxygen and carbogen
      inhalation in the spleen (both P < 0.001), liver (P = 0.002 air vs. oxygen; P =
      0.001 air vs. carbogen), skeletal muscle (both P < 0.001), and renal cortex (P =
      0.005 air vs. oxygen; P = 0.008 air vs. carbogen). No significant change in
      R(*)(2) occurred following pure oxygen in any organ. However, a significant
      increase in R(*)(2) was observed in the spleen (P < 0.001), liver (P = 0.001),
      skeletal muscle (P = 0.026), and renal cortex (P = 0.001) following carbogen
      inhalation, an opposite effect to that observed in many studies of tumor
      pathophysiology. Changes in R(1) and R(*)(2) were independent of the gas
      administration order in the spleen and skeletal muscle. These findings suggest
      that the R(1) and R(*)(2) responses to hyperoxic gases are independent biomarkers
      of oxygen physiology.

PMID- 19097213
TI  - Multiecho dixon fat and water separation method for detecting fibrofatty
      infiltration in the myocardium.
AB  - Conventional approaches for fat and water discrimination based on chemical-shift
      fat suppression have reduced ability to characterize fatty infiltration due to
      poor contrast of microscopic fat. The multiecho Dixon approach to water and fat
      separation has advantages over chemical-shift fat suppression: 1) water and fat
      images can be acquired in a single breathhold, avoiding misregistration; 2) fat
      has positive contrast; 3) the method is compatible with precontrast and late
      enhancement imaging, 4) less susceptible to partial-volume effects, and 5) robust
      in the presence of background field variation; and 6) for the bandwidth
      implemented, chemical-shift artifact is decreased. The proposed technique was
      applied successfully in all 28 patients studied. This included 10 studies with
      indication of coronary artery disease (CAD), of which four cases with chronic
      myocardial infarction (MI) exhibited fatty infiltration; 13 studies to rule out
      arrhythmogenic right ventricular cardiomyopathy (ARVC), of which there were three
      cases with fibrofatty infiltration and two confirmed with ARVC; and five cases of
      cardiac masses (two lipomas). The precontrast contrast-to-noise ratio (CNR) of
      intramyocardial fat was greatly improved, by 240% relative to conventional fat
      suppression. For the parameters implemented, the signal-to-noise ratio (SNR) was
      decreased by 30% relative to conventional late enhancement. The multiecho Dixon
      method for fat and water separation provides a sensitive means of detecting
      intramyocardial fat with positive signal contrast.

PMID- 19097214
TI  - Whole-body imaging at 7T: preliminary results.
AB  - The objective of this study was to investigate the feasibility of whole-body
      imaging at 7T. To achieve this objective, new technology and methods were
      developed. Radio frequency (RF) field distribution and specific absorption rate
      (SAR) were first explored through numerical modeling. A body coil was then
      designed and built. Multichannel transmit and receive coils were also developed
      and implemented. With this new technology in hand, an imaging survey of the
      "landscape" of the human body at 7T was conducted. Cardiac imaging at 7T appeared
      to be possible. The potential for breast imaging and spectroscopy was
      demonstrated. Preliminary results of the first human body imaging at 7T suggest
      both promise and directions for further development.

PMID- 19097215
TI  - Implementation of three-dimensional wavelet encoding spectroscopic imaging: in
      vivo application and method comparison.
AB  - We have recently proposed a two-dimensional Wavelet Encoding-Spectroscopic
      Imaging (WE-SI) technique as an alternative to Chemical Shift Imaging (CSI), to
      reduce acquisition time and crossvoxel contamination in magnetic resonance
      spectroscopic imaging (MRSI). In this article we describe the extension of the WE
      SI technique to three dimensions and its implementation on a clinical 1.5 T
      General Electric (GE) scanner. Phantom and in vivo studies are carried out to
      demonstrate the usefulness of this technique for further acquisition time
      reduction with low voxel contamination. In wavelet encoding, a set of dilated and
      translated prototype functions called wavelets are used to span a localized space
      by dividing it into a set of subspaces with predetermined sizes and locations. In
      spectroscopic imaging, this process is achieved using radiofrequency (RF) pulses
      with profiles resembling the wavelet shapes. Slice selective excitation and
      refocusing RF pulses, with single-band and dual-band profiles similar to Haar
      wavelets, are used in a modified PRESS sequence to acquire 3D WE-SI data. Wavelet
      dilation and translation are achieved by changing the strength of the
      localization gradients and frequency shift of the RF pulses, respectively. The
      desired spatial resolution in each direction sets the corresponding number of
      dilations (increases in the localization gradients), and consequently, the number
      of translations (frequency shift) of the Haar wavelets (RF pulses), which are
      used to collect magnetic resonance (MR) signals from the corresponding subspaces.
      Data acquisition time is reduced by using the minimum recovery time (TR(min)),
      also called effective time, when successive MR signals from adjacent subspaces
      are collected. Inverse wavelet transform is performed on the acquired data to
      produce metabolite maps. The proposed WE-SI method is compared in terms of
      acquisition time, pixel bleed, and signal-to-noise ratio to the CSI technique.
      The study outcome shows that 3D WE-SI provides accurate results while reducing
      both acquisition time and voxel contamination.

PMID- 19097216
TI  - k-t FOCUSS: a general compressed sensing framework for high resolution dynamic
      MRI.
AB  - A model-based dynamic MRI called k-t BLAST/SENSE has drawn significant attention
      from the MR imaging community because of its improved spatio-temporal resolution.
      Recently, we showed that the k-t BLAST/SENSE corresponds to the special case of a
      new dynamic MRI algorithm called k-t FOCUSS that is optimal from a compressed
      sensing perspective. The main contribution of this article is an extension of k-t
      FOCUSS to a more general framework with prediction and residual encoding, where
      the prediction provides an initial estimate and the residual encoding takes care
      of the remaining residual signals. Two prediction methods, RIGR and motion
      estimation/compensation scheme, are proposed, which significantly sparsify the
      residual signals. Then, using a more sophisticated random sampling pattern and
      optimized temporal transform, the residual signal can be effectively estimated
      from a very small number of k-t samples. Experimental results show that excellent
      reconstruction can be achieved even from severely limited k-t samples without
      aliasing artifacts.

PMID- 19097217
TI  - STAR and STARFIRE for flow-dependent and flow-independent noncontrast carotid
      angiography.
AB  - Signal Targeting with Alternating Radiofrequency (STAR) and STAR and Flow
      Independent Relaxation Enhancement (STARFIRE) are noncontrast methods for flow
      dependent and flow-independent magnetic resonance angiography (MRA). The methods
      rely on the acquisition and complex subtraction of two image sets alternately
      labeled by spatially selective or spatially nonselective inversion radio
      frequency (RF) pulses. Experimental results show that the RF labeling period
      affects the extent of the carotid vessels seen with STAR imaging, and the
      conspicuity of cerebrospinal fluid (CSF) and fat in the STARFIRE images. Both
      methods were found to provide more detailed depiction of the carotid arteries
      than the alternative noncontrast MRA technique of time-of-flight (TOF)
      angiography.

PMID- 19097218
TI  - Mechanical model of neural tissue displacement during Lorentz effect imaging.
AB  - Allen Song and coworkers recently proposed a method for MRI detection of
      biocurrents in nerves called "Lorentz effect imaging." When exposed to a magnetic
      field, neural currents are subjected to a Lorentz force that moves the nerve. If
      the displacement is large enough, an artifact is predicted in the MR signal. In
      this work, the displacement of a nerve of radius a in a surrounding tissue of
      radius b and shear modulus mu is analyzed. The nerve carries a current density J
      and lies in a magnetic field B. The solution to the resulting elasticity problem
      indicates that the nerve moves a distance BJ/4mu a2ln(b/a). Using realistic
      parameters for a human median nerve in a 4T field, this calculated displacement
      is 0.013 microm or less. The distribution of displacement is widespread
      throughout the tissue, and is not localized near the nerve. This displacement is
      orders of magnitude too small to be detected by conventional MRI methods.

PMID- 19097219
TI  - 3D blood flow characteristics in the carotid artery bifurcation assessed by flow
      sensitive 4D MRI at 3T.
AB  - To determine three-dimensional (3D) blood flow patterns in the carotid
      bifurcation, 10 healthy volunteers and nine patients with internal carotid artery
      (ICA) stenosis > or =50% were examined by flow-sensitive 4D MRI at 3T. Absolute
      and mean blood velocities, pulsatility index (PI), and resistance index (RI) were
      measured in the common carotid arteries (CCAs) by duplex sonography (DS) and
      compared with flow-sensitive 4D MRI. Furthermore, 3D MRI blood flow patterns in
      the carotid bifurcation of volunteers and patients before and after
      recanalization were graded by two independent readers. Blood flow velocities
      measured by MRI were 31-39% lower than in DS. However, PI and RI differed by only
      13-16%. Rating of 3D flow characteristics in the ICA revealed consistent patterns
      for filling and helical flow in volunteers. In patients with ICA stenosis, 3D
      blood flow visualization was successfully employed to detect markedly altered
      filling and helical flow patterns (forward-moving spiral flow) in the ICA bulb
      and to evaluate the effect of revascularization, which restored filling and
      helical flow. Our results demonstrate the feasibility of flow-sensitive 4D MRI
      for the quantification and 3D visualization of physiological and pathological
      flow patterns in the carotid artery bifurcation.

PMID- 19097220
TI  - Influence of RF spoiling on the stability and accuracy of T1 mapping based on
      spoiled FLASH with varying flip angles.
AB  - There is increasing interest in quantitative T(1) mapping techniques for a
      variety of applications. Several methods for T(1) quantification have been
      described. The acquisition of two spoiled gradient-echo data sets with different
      flip angles allows for the calculation of T(1) maps with a high spatial
      resolution and a relatively short experimental duration. However, the method
      requires complete spoiling of transverse magnetization. To achieve this goal, RF
      spoiling has to be applied. In this work it is investigated whether common RF
      spoiling techniques are sufficiently effective to allow for accurate T(1)
      quantification. It is shown that for most phase increments the apparent T(1) can
      deviate considerably from the true value. Correct results may be achieved with
      phase increments of 118.2 degrees or 121.8 degrees. However, for these values the
      method suffers from instabilities. In contrast, stable results are obtained with
      a phase increment of 50 degrees. An algorithm is presented that allows for the
      calculation of corrected T(1) maps from the apparent values. The method is tested
      both in phantom experiments and in vivo by acquiring whole-brain T(1) maps of the
      human brain.

PMID- 19097221
TI  - Imaging and analysis of lenticulostriate arteries using 7.0-Tesla magnetic
      resonance angiography.
AB  - The purpose of this study was to analyze human lenticulostriate arteries (LSAs)
      obtained non-invasively by 7.0-T MRI. A three-dimensional time-of-flight (3D TOF)
      magnetic resonance angiography (MRA) technique was used with an investigational
      7.0-T MRI scanner with a radio-frequency coil that was optimized and designed for
      angiographic purposes. We obtained images from 16 healthy volunteers (8 males and
      8 females, mean age 21 +/- 2.7 years). For direct comparison of LSA images with
      digital subtraction angiography (DSA), we also obtained 7.0-T MRA and DSA images
      from one patient, a 27-year-old woman with a posterior fossa arteriovenous
      malformation (AVM). We then analyzed the characteristics of LSAs using a custom
      data analysis method with MatLab for quantitative analysis. Analysis of LSA
      images included shape and number of branches and origins, findings that are
      essential and useful for quantification of LSA abnormalities in both healthy
      controls and patients. Ultra-high-field MRA provided clear anatomic delineation
      of the LSAs, thereby suggesting that 7.0-T MRA may be a promising technique for
      microvascular imaging of the LSAs.

PMID- 19097222
TI  - Aortic vessel wall magnetic resonance imaging at 3.0 Tesla: a reproducibility
      study of respiratory navigator gated free-breathing 3D black blood magnetic
      resonance imaging.
AB  - The purpose of this study was to evaluate a free-breathing three-dimensional (3D)
      dual inversion-recovery (DIR) segmented k-space gradient-echo (turbo field echo
      [TFE]) imaging sequence at 3T for the quantification of aortic vessel wall
      dimensions. The effect of respiratory motion suppression on image quality was
      tested. Furthermore, the reproducibility of the aortic vessel wall measurements
      was investigated. Seven healthy subjects underwent 3D DIR TFE imaging of the
      aortic vessel wall with and without respiratory navigator. Subsequently, this
      sequence with respiratory navigator was performed twice in 10 healthy subjects to
      test its reproducibility. The signal-to-noise (SNR), contrast-to-noise ratio
      (CNR), vessel wall sharpness, and vessel wall volume (VWV) were assessed. Data
      were compared using the paired t-test, and the reproducibility of VWV
      measurements was evaluated using intraclass correlation coefficients (ICCs). SNR,
      CNR, and vessel wall sharpness were superior in scans performed with respiratory
      navigator compared to scans performed without. The ICCs concerning intraobserver,
      interobserver, and interscan reproducibility were excellent (0.99, 0.94, and
      0.95, respectively). In conclusion, respiratory motion suppression substantially
      improves image quality of 3D DIR TFE imaging of the aortic vessel wall at 3T.
      Furthermore, this optimized technique with respiratory motion suppression enables
      assessment of aortic vessel wall dimensions with high reproducibility.

PMID- 19097223
TI  - Regularized sensitivity encoding (SENSE) reconstruction using Bregman iterations.
AB  - In parallel imaging, the signal-to-noise ratio (SNR) of sensitivity encoding
      (SENSE) reconstruction is usually degraded by the ill-conditioning problem, which
      becomes especially serious at large acceleration factors. Existing regularization
      methods have been shown to alleviate the problem. However, they usually suffer
      from image artifacts at high acceleration factors due to the large data
      inconsistency resulting from heavy regularization. In this paper, we propose
      Bregman iteration for SENSE regularization. Unlike the existing regularization
      methods where the regularization function is fixed, the method adaptively updates
      the regularization function using the Bregman distance at different iterations,
      such that the iteration gradually removes the aliasing artifacts and recovers
      fine structures before the noise finally comes back. With a discrepancy principle
      as the stopping criterion, our results demonstrate that the reconstructed image
      using Bregman iteration preserves both sharp edges lost in Tikhonov
      regularization and fines structures missed in total variation (TV)
      regularization, while reducing more noise and aliasing artifacts.

PMID- 19097224
TI  - 3D cine displacement-encoded MRI of pulsatile brain motion.
AB  - Pulsatile brain motion is considered to be an important mechanical link between
      blood and cerebrospinal fluid (CSF) dynamics. Like many severe brain diseases,
      different types of hydrocephalus are associated with impairment of these
      dynamics. In this work a cine displacement-encoded imaging method employing
      stimulated echoes (DENSE) and a three-dimensional (3D) segmented echo-planar
      imaging (EPI) readout for brain motion measurements in all three spatial
      directions is presented. Displacement-encoded data sets of 12 healthy volunteers
      were analyzed with respect to reproducibility, periodicity, and intra- as well as
      intersubject physiological consistency. In addition, displacement values were
      compared with data derived from phase-contrast (PC) velocity measurements in a
      subset of all measured subjects. Using DENSE, displacements as low as 0.01 mm
      could be detected and observation of the 3D pulse pressure wave propagation was
      possible. Among other parameters, peak displacements in the central brain regions
      were measured: feet-head (FH): thalamus (0.13 +/- 0.01 mm); right-left (RL):
      thalamus (0.06 +/- 0.01 mm); and anterior-posterior (AP): caudate nucleus (0.05
      +/- 0.01 mm).

PMID- 19097226
TI  - A Bayesian hierarchical model for the analysis of a longitudinal dynamic contrast
      enhanced MRI oncology study.
AB  - Imaging in clinical oncology trials provides a wealth of information that
      contributes to the drug development process, especially in early phase studies.
      This article focuses on kinetic modeling in DCE-MRI, inspired by mixed-effects
      models that are frequently used in the analysis of clinical trials. Instead of
      summarizing each scanning session as a single kinetic parameter--such as median
      k(trans) across all voxels in the tumor ROI-we propose to analyze all voxel time
      courses from all scans and across all subjects simultaneously in a single model.
      The kinetic parameters from the usual nonlinear regression model are decomposed
      into unique components associated with factors from the longitudinal study; e.g.,
      treatment, patient, and voxel effects. A Bayesian hierarchical model provides the
      framework to construct a data model, a parameter model, as well as prior
      distributions. The posterior distribution of the kinetic parameters is estimated
      using Markov chain Monte Carlo (MCMC) methods. Hypothesis testing at the study
      level for an overall treatment effect is straightforward and the patient- and
      voxel-level parameters capture random effects that provide additional information
      at various levels of resolution to allow a thorough evaluation of the clinical
      trial. The proposed method is validated with a breast cancer study, where the
      subjects were imaged before and after two cycles of chemotherapy, demonstrating
      the clinical potential of this method to longitudinal oncology studies.

PMID- 19097225
TI  - Functional brain mapping at 9.4T using a new MRI-compatible electrode chronically
      implanted in rats.
AB  - There is a need for acute and chronic stimulation of the brain within the MRI for
      studies of epilepsy, as well as deep brain stimulation for movement and
      behavioral disorders. This work describes the production and characteristics of
      carbon fiber-based electrodes for acute and chronic stimulation in the brain.
      Increasing MRI field strengths are making it increasingly difficult to introduce
      foreign objects without a susceptibility artifact. We describe the production of,
      and the characteristics of carbon fiber-based electrodes. These are biocompatible
      and can be implanted for chronic studies. We show the use of these electrodes at
      9.4T for studying functional activation. Data are presented showing regional
      connectivity. Activation not only occurs near the electrode, but at sites distant
      and often contralateral to the electrode. In addition, there were sites showing
      strong negative activation to stimulation both with direct stimulation and during
      a kindling-associated seizure.

PMID- 19097227
TI  - Efficient multiple acquisitions by Skipped Phase Encoding and Edge Deghosting
      (SPEED) using shared spatial information.
AB  - The fast MRI method of Skipped Phase Encoding and Edge Deghosting (SPEED) is
      further developed to accelerate multiple acquisitions. In a single acquisition,
      SPEED first acquires three sparse ghosted edge maps with an undersampling factor
      of N/3, which are modeled with a double-layer structure and described by three
      equations with two unknown ghosts, each with a unique ghost order index. By
      minimizing least-square-error, a pair of ghost order indexes is determined. Based
      on them, the two corresponding ghosts are resolved, leading to a deghosted image.
      In this case, three equations are needed to determine the ghost order index,
      while only two equations are required to resolve the two ghosts. This shows both
      inefficiency and potential. Multiple acquisitions often contain similar spatial
      information. The similarities can be used to improve efficiency by sharing the
      ghost order index among different acquisitions, leading to acceleration factors
      greater than that achievable with single acquisition.

PMID- 19097228
TI  - Inherent fat cancellation in complementary spatial modulation of magnetization.
AB  - An efficient fat suppression method is presented for MR tagging with
      complementary spatial modulation of magnetization (CSPAMM). In this method, the
      complementary modulation is applied to the water content of the tissues, while in
      phase modulation is applied to the fat content. Therefore, during image
      reconstruction, the subtraction of the acquired images increases the tagging
      contrast of the water while cancels the tagging lines of the fat. Compared with
      the existing fat suppression techniques, the proposed method allows imaging with
      higher temporal resolution and shorter echo-time without increasing the scan
      time. The feasibility of applying the method on 1.5 Tesla (T) and 3.0T scanners
      has been tested using MR phantom and human volunteers.

PMID- 19097229
TI  - Diffuse colitis cystica profunda in a patient with ulcerative colitis.

PMID- 19097230
TI  - Fibrosing colonopathy associated with treatment with enteric-coated mesalazine
      pills.

PMID- 19097231
TI  - Give me prednisone and give me death.

PMID- 19097232
TI  - Design of cosine modulated very selective suppression pulses for MR spectroscopic
      imaging at 3T.
AB  - The advantages of using a 3 Tesla (T) scanner for MR spectroscopic imaging (MRSI)
      of brain tissue include improved spectral resolution and increased sensitivity.
      Very selective saturation (VSS) pulses are important for maximizing selectivity
      for PRESS MRSI and minimizing chemical shift misregistration by saturating
      signals from outside the selected region. Although three-dimensional (3D) PRESS
      MRSI is able to provide excellent quality metabolic data for patients with brain
      tumors and has been shown to be important for defining tumor burden, the method
      is currently limited by how much of the anatomic lesion can be covered within a
      single examination. In this study we designed and implemented cosine modulated
      VSS pulses that were optimized for 3T MRSI acquisitions. This provided improved
      coverage and suppression of unwanted lipid signals with a smaller number of
      pulses. The use of the improved pulse sequence was validated in volunteer
      studies, and in clinical 3D MRSI exams of brain tumors.

PMID- 19097234
TI  - Perfusion precision in bolus-tracking MRI: estimation using the wild-bootstrap
      method.
AB  - Bolus-tracking MRI involves the bolus injection of contrast agent, and the
      resultant concentration time course can be used to calculate perfusion by
      deconvolution analysis. However, most deconvolution methods do not provide a
      measure of precision. Precision could be estimated from many repeated
      measurements; however, this would involve a series of successive bolus
      injections, which is not a feasible option in practice due to contrast agent dose
      constraints. In this work, a method is presented to estimate precision in bolus
      tracking MRI using the wild-bootstrap method. This approach is able to estimate
      the uncertainty in perfusion measurements from the data acquired during a single
      bolus of contrast agent injection. The methodology was assessed using numerical
      simulations and applied to real data with a range of image qualities. The method
      is shown to provide useful estimates of precision, and the results from real data
      were consistent with the underlying MRI data quality. The methodology provides an
      important complementary tool in clinical and research applications of bolus
      tracking MRI.

PMID- 19097233
TI  - Initial results of cardiac imaging at 7 Tesla.
AB  - This work reports preliminary results from the first human cardiac imaging at 7
      Tesla (T). Images were acquired using an eight-channel transmission line (TEM)
      array together with local B(1) shimming. The TEM array consisted of anterior and
      posterior plates closely positioned to the subjects' thorax. The currents in the
      independent elements of these arrays were phased to promote constructive
      interference of the complex, short wavelength radio frequency field over the
      entire heart. Anatomic and functional images were acquired within a single breath
      hold to reduce respiratory motion artifacts while a vector cardiogram (VCG) was
      used to mitigate cardiac motion artifacts and gating. SAR exposure was modeled,
      monitored, and was limited to FDA guidelines for the human torso in subject
      studies. Preliminary results including short-axis and four-chamber VCG-retrogated
      FLASH cines, as well as, short-axis TSE images demonstrate the feasibility of
      safe and accurate human cardiac imaging at 7T.

PMID- 19097235
TI  - Rapid monitoring of oxygenation by 19F magnetic resonance imaging: Simultaneous
      comparison with fluorescence quenching.
AB  - The aim of this study was to develop an MRI fluorocarbon oximetry technique using
      snapshot inversion recovery and compare it with fluorescence quenching fiber
      optic probe oximetry (OxyLite) performed simultaneously in experimental mouse
      tumors. The oxygen reporter probe hexafluorobenzene (HFB) was injected directly
      into the tumors, along with the insertion of the OxyLite probe. Tumor oxygenation
      (pO(2)) was modified using carbogen or lethal doses of the anesthetic gas. MRI
      pO(2) maps were generated in 1.5 min with an in-plane spatial resolution of 1.88
      mm. MRI and OxyLite showed consistent baseline and postmortem pO(2) values.
      Increases in tumor pO(2) during carbogen breathing showed similar kinetics for
      the two methods. The pO(2) values observed using the OxyLite corresponded with
      relatively hypoxic values observed by MRI. The apparent discrepancy between mean
      values might be due to the difference in sampling volumes of the techniques and
      the observation of multiple locations using (19)F MRI versus a single location
      using the large optical fiber. Overall, the present method provides a rapid way
      to map the tumor oxygenation and is particularly suitable to monitor acute
      changes of pO(2) in tumors.

PMID- 19097236
TI  - MR elastography of the human heart: noninvasive assessment of myocardial
      elasticity changes by shear wave amplitude variations.
AB  - Many cardiovascular diseases and disorders are associated with hemodynamic
      dysfunction. The heart's ability to contract and pump blood through the vascular
      system primarily depends on the elasticity of the myocardium. This article
      introduces a magnetic resonance elastography (MRE) technique that allows
      noninvasive and time-resolved measurement of changes in myocardial elasticity
      over the cardiac cycle. To this end, low-frequency shear vibrations of 24.3 Hz
      were induced in the human heart via the anterior chest wall. An
      electrocardiograph (ECG)-triggered, steady-state MRE sequence was used to capture
      shear oscillations with a frame rate of eight images per vibration cycle. The
      time evolution of 2D-shear wave fields was observed in two imaging planes through
      the short axis of the heart in six healthy volunteers. Correlation analysis
      revealed that wave amplitudes were modulated in synchrony to the heartbeat with
      up to 2.45 +/- 0.18 higher amplitudes during diastole than during systole
      (interindividual mean +/- SD). The reduction of wave amplitudes started at 75 +/-
      9 ms prior to changes in left ventricular diameter occurring at the beginning of
      systole. Analysis of this wave amplitude alteration using a linear elastic
      constitutive model revealed a maximum change in the myocardial wall stiffness of
      a factor of 37.7 +/- 10.6 during the cardiac cycle.

PMID- 19097237
TI  - Phase labeling using sensitivity encoding (PLUS): data acquisition and image
      reconstruction for geometric distortion correction in EPI.
AB  - Geometric distortion caused by magnetic field inhomogeneity is generally an
      inevitable tradeoff for fast MRI acquisitions using echo-planar imaging. Most of
      the existing distortion-correction techniques require separate scans for field
      maps in order to correct the distortion contained in a measurement. A drawback of
      these current techniques is that the field map scans and the measurement can
      capture different patient positions, which invalidates the stationary condition.
      A new method was developed in this work to correct geometric distortion by using
      local phase shifts derived directly from the measurement itself, without the need
      of extra field map scans. This self-sufficient method takes advantage of parallel
      imaging and k-space trajectory modification to produce multiple images from a
      single acquisition. The measurement is also used to derive sensitivity maps for
      parallel imaging reconstruction. The derived phase shifts are retrospectively
      applied to the measurement for correction of geometric distortion in the
      measurement itself. The proposed method was successfully demonstrated using
      experimental data from a phantom and a human brain.

PMID- 19097238
TI  - On the measurement of absolute cerebral blood volume (CBV) using vascular-space
      occupancy (VASO) MRI.
AB  - Recently, a vascular-space-occupancy (VASO) MRI technique was developed for
      quantitative assessment of cerebral blood volume (CBV). This method uses the T(1)
      shortening effect of gadolinium diethylenetriamine pentaacetic acid (Gd-DTPA)
      with imaging parameters chosen that null the precontrast blood magnetization but
      allow the postcontrast blood magnetization to recover to equilibrium. A key
      advantage of VASO CBV estimation is that it provides a straightforward procedure
      for converting MR signals to absolute physiologic values. However, as with other
      T(1)-based steady-state approaches, several important factors need to be
      considered that influence the accuracy of CBV values obtained with VASO MRI.
      Here, the transverse relaxation (T(2)/T(2) (*)) effect in VASO MRI was
      investigated using multiecho spin-echo and gradient-echo experiments, resulting
      in underestimation of CBV by 14.9% +/- 1.1% and 16.0% +/- 2.5% for spin echo (TE
      = 10 ms) and gradient echo (TE = 6 ms), respectively. In addition, the influence
      of contrast agent clearance was studied by acquiring multiple postcontrast VASO
      images at 2.2-min intervals, which showed that the concentration of Gd-DTPA in
      the first 14 min (single dose) was sufficient for the blood magnetization to
      fully recover to equilibrium. Finally, the effect of vascular Gd-DTPA leakage was
      assessed for scalp tissue, and signal extrapolation as a function of
      postinjection time was demonstrated to be useful in minimizing the associated
      errors. Specific recommendations for VASO MRI acquisition and processing
      strategies are provided.

PMID- 19097239
TI  - Magnetic resonance imaging quantification of left ventricular dysfunction
      following coronary microembolization.
AB  - Microembolization is common after coronary interventions, and therefore this MRI
      study aimed to quantify the effect of coronary microembolization on left
      ventricular (LV) function. The left anterior descending artery (LAD) was
      selectively catheterized in an XMR suite (Philips Medical Systems, Best, The
      Netherlands) in eight pigs to deliver MR contrast media to measure the LAD
      territory using first-pass perfusion and for intracoronary delivery of the
      embolic agent. Cine, tagged, and delayed contrast-enhanced MRI (DCE-MRI) was
      performed to assess LV volumes, ejection fraction, radial and circumferential
      strain, and viability at baseline, 1 h, and 1 week after microembolization.
      Histopathology and histochemical staining were used to characterize and measure
      the extent of microinfarction. The LAD territory was 35% +/- 2% LV mass. Patchy
      microinfarction on DCE-MRI at 1 week was 22.0% +/- 3.6% LAD territory (7.5% LV
      mass). Microembolization caused persistent decline in ejection fraction (baseline
      = 49% +/- 1%, 1 h = 29% +/- 1%, P = 0.02 and 1 week = 36% +/- 1%, P = 0.03) and
      increased end-diastolic (79.6 +/- 3.9 ml, 85.5 +/- 4.5 ml, P = 0.03 and 92.4 +/-
      6.2 ml, P = 0.06, respectively) and end-systolic (40.8 +/- 2.1 ml, 60.2 +/- 3.4
      ml, P = 0.02 and 59.3 +/- 4.8 ml, P = 0.03, respectively) volumes. The
      microembolized territory was manifested as dysfunctional regions for 1 week on
      cine and tagged MRI. Histopathology revealed occlusive microemboli surrounded by
      necrotic tissue undergoing repair. Microinfarction was visualized after coronary
      microembolization and caused LV dysfunction disproportionate to the size of
      myocardial damage. It also changed LV geometry and decreased radial and
      circumferential strain over the course of 1 week.

PMID- 19097240
TI  - Rigid-body motion correction with self-navigation MRI.
AB  - The use of phase correlation to detect rigid-body translational motion is
      reviewed and applied to individual echotrains in turbo-spin-echo data
      acquisition. It is shown that when the same echotrain is acquired twice, the
      subsampled correlation provides an array of delta-functions, from which the
      motion that occurred between the acquisitions of the two echotrains can be
      measured. It is shown further that a similar correlation can be found between two
      sets of equally spaced measurements that are adjacent in k-space. By measuring
      the motion between all adjacent pairs of k-space subgroups, the complete motion
      history of a subject can be determined and the motion artifacts in the image can
      be corrected. Some of the limiting factors in using this technique are
      investigated with turbo-spin-echo head and hand images.

PMID- 19097241
TI  - On using T2 to assess extrinsic magnetic field inhomogeneity effects on T2*
      measurements in myocardial siderosis in thalassemia.
AB  - Magnetic resonance T(2)* has been validated as a noninvasive means of assessing
      myocardial iron overload. However, the effect on myocardial T(2)* of factors such
      as shimming, variations in capillary geometry, and susceptibility in relation to
      the effects of iron has not been fully clarified. Since T(2) is not affected by
      extrinsic magnetic field inhomogeneity and has different sensitivity to capillary
      geometry, investigation into the in vivo relationship between myocardial T(2)*
      and T(2) measurements can shed light on this important issue. This study was
      performed in 136 thalassemia patients. The myocardial T(2) and T(2)* thresholds
      for normality created identical no-iron-overload and iron-overloaded patient
      groups. In the no-iron group, there was no correlation between myocardial T(2)
      and T(2)*. In the iron-overloaded patients, there was a linear correlation (R(2)
      = 0.89) between myocardial T(2)* and T(2) measurements, which indicates that the
      iron deposition is the dominant factor in determining these two relaxation values
      in this scenario.

PMID- 19097242
TI  - Quantification of myocardial perfusion using free-breathing MRI and prospective
      slice tracking.
AB  - Quantification of myocardial perfusion using first-pass magnetic resonance
      imaging (MRI) is hampered by respiratory motion of the heart. Prospective slice
      tracking (PST) potentially overcomes this problem, and may provide an attractive
      alternative or supplement to current breath-hold techniques. This study
      demonstrates the feasibility of patient-adapted 3D PST on a 3.0 Tesla MR system.
      Eight patients underwent free-breathing studies of myocardial perfusion,
      simultaneously collecting data with and without PST. On average, PST reduced
      residual in-plane motion by a factor of 2, compared to the noncorrected images,
      resulting in a fourfold improvement of perfusion measurements. In addition, a
      comparison of perfusion measurements performed with and without PST showed that
      through-plane motion can contaminate measurements of myocardial perfusion.
      However, the quality of the navigator echoes on this field strength constituted a
      major source of error and needs further improvement to increase the accuracy and
      robustness of the method.

PMID- 19097243
TI  - Fat/water separation using a concentric rings trajectory.
AB  - The concentric rings two-dimensional (2D) k-space trajectory enables flexible
      trade-offs between image contrast, signal-to-noise ratio (SNR), spatial
      resolution, and scan time. However, to realize these benefits for in vivo imaging
      applications, a robust method is desired to deal with fat signal in the acquired
      data. Multipoint Dixon techniques have been shown to achieve uniform fat
      suppression with high SNR-efficiency for Cartesian imaging, but application of
      these methods for non-Cartesian imaging is complicated by the fact that fat off
      resonance creates significant blurring artifacts in the reconstruction. In this
      work, two fat-water separation algorithms are developed for the concentric rings.
      A retracing design is used to sample rings near the center of k-space through
      multiple revolutions to characterize the fat-water phase evolution difference at
      multiple time points. This acquisition design is first used for multipoint Dixon
      reconstruction, and then extended to a spectroscopic approach to account for the
      trajectory's full evolution through 3D k-t space. As the trajectory is resolved
      in time, off-resonance effects cause shifts in frequency instead of spatial
      blurring in 2D k-space. The spectral information can be used to assess field
      variation and perform robust fat-water separation. In vivo experimental results
      demonstrate the effectiveness of both algorithms.

PMID- 19097244
TI  - Transverse relaxation and magnetization transfer in skeletal muscle: effect of
      pH.
AB  - Exercise increases the intracellular T(2) (T(2,i)) of contracting muscles. The
      mechanism(s) for the T(2,i) increase have not been fully described, and may
      include increased intracellular free water and acidification. These changes may
      alter chemical exchange processes between intracellular free water and proteins.
      In this study, the hypotheses were tested that (a) pH changes T(2,i) by affecting
      the rate of magnetization transfer (MT) between free intracellular water and
      intracellular proteins, and (b) the magnitude of the T(2,i) effect depends on
      acquisition mode (localized or nonlocalized) and echo spacing. Frog gastrocnemius
      muscles were excised and their intracellular pH was either kept at physiological
      pH (7.0) or modified to model exercising muscle (pH 6.5). The intracellular
      transverse relaxation rate (R(2,i) = 1/T(2,i)) always decreased in the acidic
      muscles, but the changes were greater when measured using more rapid refocusing
      rates. The MT rate from the macromolecular proton pool to the free water proton
      pool, its reverse rate, and the spin-lattice relaxation rate of water decreased
      in acidic muscles. It is concluded that intracellular acidification alters the
      R(2,i) of muscle water in a refocusing rate-dependent manner, and that the R(2,i)
      changes are correlated with changes in the MT rate between macromolecules and
      free intracellular water.

PMID- 19097245
TI  - Single-shot magnetic resonance spectroscopic imaging with partial parallel
      imaging.
AB  - A magnetic resonance spectroscopic imaging (MRSI) pulse sequence based on proton
      echo-planar-spectroscopic-imaging (PEPSI) is introduced that measures two
      dimensional metabolite maps in a single excitation. Echo-planar spatial-spectral
      encoding was combined with interleaved phase encoding and parallel imaging using
      SENSE to reconstruct absorption mode spectra. The symmetrical k-space trajectory
      compensates phase errors due to convolution of spatial and spectral encoding.
      Single-shot MRSI at short TE was evaluated in phantoms and in vivo on a 3-T whole
      body scanner equipped with a 12-channel array coil. Four-step interleaved phase
      encoding and fourfold SENSE acceleration were used to encode a 16 x 16 spatial
      matrix with a 390-Hz spectral width. Comparison with conventional PEPSI and PEPSI
      with fourfold SENSE acceleration demonstrated comparable sensitivity per unit
      time when taking into account g-factor-related noise increases and differences in
      sampling efficiency. LCModel fitting enabled quantification of inositol, choline,
      creatine, and N-acetyl-aspartate (NAA) in vivo with concentration values in the
      ranges measured with conventional PEPSI and SENSE-accelerated PEPSI. Cramer-Rao
      lower bounds were comparable to those obtained with conventional SENSE
      accelerated PEPSI at the same voxel size and measurement time. This single-shot
      MRSI method is therefore suitable for applications that require high temporal
      resolution to monitor temporal dynamics or to reduce sensitivity to tissue
      movement.

PMID- 19097246
TI  - High-field diffusion MR histology: image-based correction of eddy-current ghosts
      in diffusion-weighted rapid acquisition with relaxation enhancement (DW-RARE).
AB  - High-resolution, diffusion-weighted (DW) MR microscopy is gaining increasing
      acceptance as a nondestructive histological tool for the study of fixed tissue
      samples. Spin-echo sequences are popular for high-field diffusion imaging due to
      their high tolerance to B(0) field inhomogeneities. Volumetric DW rapid
      acquisition with relaxation enhancement (DW-RARE) currently offers the best
      tradeoff between imaging efficiency and image quality, but is relatively
      sensitive to residual eddy-current effects on the echo train phase, resulting in
      encoding direction-dependent ghosting in the DW images. We introduce two
      efficient, image-based phase corrections for ghost artifact reduction in DW-RARE
      of fixed tissue samples, neither of which require navigator echo acquisition.
      Both methods rely on the phase difference in k-space between the unweighted
      reference image and a given DW image and assume a constant, per-echo phase error
      arising from residual eddy-current effects in the absence of sample motion.
      Significant qualitative and quantitative ghost artifact reductions are
      demonstrated for individual DW and calculated diffusion tensor images.

PMID- 19097247
TI  - Increasing spatial coverage for high-resolution functional MRI.
AB  - For high-resolution functional MRI (fMRI) studies, one of the major challenges is
      limited spatial coverage, which results because of the tradeoffs between temporal
      resolution and covering more k-space. Given the same temporal resolution, fewer
      slices can be collected for high-resolution fMRI. If the number of slices is not
      large enough to cover all regions of interest, additional scans may become
      necessary, which increases both the total scan time and the complexity of
      interpreting data. In this work, we propose a method that combines the
      undersampled 3D stack-of-spirals acquisition method with the UNFOLD technique to
      significantly increase the spatial coverage for high-resolution fMRI.
      Undersampling allows more slices to be fit into a given temporal resolution. The
      signal-to-noise ratio (SNR) drop associated with undersampling can be compensated
      by the increase in the excited volume in 3D acquisitions. Theoretical analysis
      shows that although there is a negligible increase in temporal coherence due to
      spectral filtering in the UNFOLD technique, twice the spatial coverage can be
      achieved given the same total scan time and similar quality of activation maps,
      which was confirmed by experiments on normal subjects.

PMID- 19097248
TI  - k-TE generalized autocalibrating partially parallel acquisition (GRAPPA) for
      accelerated multiple gradient-recalled echo (MGRE) R2* mapping in the abdomen.
AB  - Multiple gradient-recalled echo (MGRE) methods are commonly used for abdominal
      R(2)* mapping. Accelerated MGRE acquisitions would offer the potential to shorten
      requisite breathhold times and/or increase spatial resolution and coverage. In
      both phantom and normal volunteer studies, view-sharing (VS) methods, generalized
      autocalibrating partially parallel acquisition (GRAPPA) methods, and newly
      proposed k-echo time (k-TE) GRAPPA methods were compared for the purpose of
      accelerating MGRE acquisitions. Utilization of water-selective spatial spectral
      excitation pulses reduced artifact levels for both VS and k-TE GRAPPA approaches.
      VS approaches were found to be highly sensitive to off-resonance effects,
      particularly at increasing acceleration rates. k-TE GRAPPA significantly reduced
      residual artifact levels compared to GRAPPA approaches while improving the
      accuracy of accelerated abdominal R(2)* measurements. These initial feasibility
      studies demonstrate that k-TE GRAPPA is an effective method to reduce scan times
      during abdominal R(2)*-mapping procedures.

PMID- 19097249
TI  - Three-dimensional spatial and temporal temperature control with MR thermometry
      guided focused ultrasound (MRgHIFU).
AB  - High-intensity focused ultrasound (HIFU) is an efficient noninvasive technique
      for local heating. Using MRI thermal maps, a proportional, integral, and
      derivative (PID) automatic temperature control was previously applied at the
      focal point, or at several points within a plane perpendicular to the beam axis
      using a multispiral focal point trajectory. This study presents a flexible and
      rapid method to extend the spatial PID temperature control to three dimensions
      during each MR dynamic. The temperature in the complete volume is regulated by
      taking into account the overlap effect of nearby sonication points, which tends
      to enlarge the heated area along the beam axis. Volumetric temperature control in
      vitro in gel and in vivo in rabbit leg muscle was shown to provide temperature
      control with a precision close to that of the temperature MRI measurements. The
      proposed temperature control ensures heating throughout the volume of interest of
      up to 1 ml composed of 287 voxels with 95% of the energy deposited within its
      boundaries and reducing the typical average temperature overshoot to 1 degrees C.

PMID- 19097250
TI  - Lung imaging under free-breathing conditions.
AB  - Respiratory motion and pulsatile blood flow can generate artifacts in
      morphological and functional lung imaging. Total acquisition time, and thus the
      achievable signal to noise ratio, is limited when performing breath-hold and/or
      electrocardiogram-triggered imaging. To overcome these limitations, imaging
      during free respiration can be performed using respiratory gating/triggering
      devices or navigator echoes. However, these techniques provide only poor gating
      resolution and can induce saturation bands and signal fluctuations into the lung
      volume. In this work, acquisition schemes for nonphase encoded navigator echoes
      were implemented into different sequences for morphological and functional lung
      imaging at 1.5 Tesla (T) and 0.2T. The navigator echoes allow monitoring of
      respiratory motion and provide an ECG-trigger signal for correction of the heart
      cycle without influencing the imaged slices. Artifact free images acquired during
      free respiration using a 3D GE, 2D multislice TSE or multi-Gradient Echo sequence
      for oxygen-enhanced T(2)(*) quantification are presented.

PMID- 19097252
TI  - Alzheimer's disease.  New research brings hope.

PMID- 19097251
TI  - Conditional estimation of sensitivity and specificity from a phase 2 biomarker
      study allowing early termination for futility.
AB  - Development of a disease screening biomarker involves several phases. In phase 2
      its sensitivity and specificity is compared with established thresholds for
      minimally acceptable performance. Since we anticipate that most candidate markers
      will not prove to be useful and availability of specimens and funding is limited,
      early termination of a study is appropriate, if accumulating data indicate that
      the marker is inadequate. Yet, for markers that complete phase 2, we seek
      estimates of sensitivity and specificity to proceed with the design of subsequent
      phase 3 studies. We suggest early stopping criteria and estimation procedures
      that adjust for bias caused by the early termination option. An important aspect
      of our approach is to focus on properties of estimates conditional on reaching
      full study enrollment. We propose the conditional-UMVUE and contrast it with
      other estimates, including naive estimators, the well-studied unconditional-UMVUE
      and the mean and median Whitehead-adjusted estimators. The conditional-UMVUE
      appears to be a very good choice.

PMID- 19097253
TI  - Proceedings of the Third International Moscow Conference on Computational
      Molecular Biology. July 27-31, 2007. Moscow, Russia.

PMID- 19097254
TI  - Current approach to the diagnosis and treatment of gastrointestinal system
      diseases. Proceedings of the 18th World Congress of the International Association
      of Surgeons, Gastroenterologists and Oncologists. October 8-11, 2008. Istanbul,
      Turkey.

PMID- 19097256
TI  - Selected papers from the 28th Annual Conference on Peritoneal Dialysis, March 2
      4, 2008. Orlando, Florida, USA.

PMID- 19097255
TI  - From infertility treatment to reproductive health. Proceedings of an
      international forum. October 3-4, 2008. Milan, Italy.

PMID- 19097257
TI  - Proceedings of MOTHIS (Model-Based Design on the Workshop of Trustworthy
      Information Systems) 2007. October 2007. Nashville, Tennessee, USA.

PMID- 19097258
TI  - [Papers from the 9th Congress of the German Interdisciplinary Society for
      Intensive and Emergency Medicine, 3-6 December, 2008. Hamburg, Germany].

PMID- 19097259
TI  - Addendum to Fragrance material review on linalool.
AB  - A Fragrance material review on linalool was published by Letizia et al. in Food
      and Chemical Toxicology 41 (2003) 943-964. This addendum to the earlier
      publication will only report studies that were conducted after the Fragrance
      material review was published.

PMID- 19097260
TI  - Patient guide to the prevention and management of pediatric obesity.

PMID- 19097261
TI  - FDA approves darunavir.

PMID- 19097263
TI  - BIOGEOMON. Proceedings of the 5th International Symposium on Ecosystem Behavior,
      June 25-30, 2006, Santa Cruz, California, USA.

PMID- 19097262
TI  - No hepatotoxicity found for etravirine.

PMID- 19097264
TI  - Abstracts of the 13th Italian Cystic Fibrosis Conference, 30 November-2 December
      2007, Milan, Italy.

PMID- 19097265
TI  - Abstracts from the XXVI CINP (Collegium Internationale Neuro
      psychopharmacologium) Congress, 13-17 July 2008, Munich, Germany.

PMID- 19097266
TI  - Sacrococcygeal pilonidal sinus disease.

PMID- 19097267
TI  - Sentinel lymph node biopsy after preoperative chemotherapy for breast cancer:
      findings from the Austrian Sentinel Node Study Group.
AB  - BACKGROUND: Sentinel lymph node biopsy (SLNB) has become an accurate alternative
      to axillary lymph node dissection for early breast cancer. However, data are
      still insufficient as regards the combination of SLNB with preoperative
      chemotherapy (PC). METHODS: The Austrian Sentinel Node Study Group investigated
      167 patients who underwent SLNB and axillary lymph node dissection after 3 to 6
      courses of PC. SLNB was limited to patients with a clinically negative axilla
      after PC. Blue dye was used in 29 cases (17%), and tracers were used in 20 (12%).
      A combination of the two methods was applied in most patients (n = 120; 72%).
      RESULTS: At least 1 sentinel lymph node (SLN) was identified in 144 patients
      (identification rate, 85%): in 86% by blue dye alone, in 65% by tracers alone,
      and in 88% by a combination of methods. The SLN was positive in 70 women (42%)
      and was the only positive node with otherwise negative axillary nodes in 39
      patients (23%). In 6 cases, the SLN was diagnosed as negative although tumor
      infiltration was detected in an upper node of the axillary basin (false-negative
      rate, 8%; 6 of 76 patients; sensitivity, 92%). At least 62 patients (37%) were
      free of tumor cells in the SLN and in the axillary nodes. CONCLUSION: The results
      of SLNB after PC are comparable to the results of SLNB without PC. Further
      investigation in a prospective setting is warranted to confirm these promising
      results.

PMID- 19097268
TI  - The World Federation of Societies of  Anaesthesiologists and Pediatric
      Anesthesia.
AB  - The World Federation of Societies of Anaesthesiologists (WFSA) is an organization
      whose principal goal is to improve the standard of anesthesia worldwide. The
      education and pediatric committees focus on the needs of pediatric patients in
      developing countries. Subspecialty training in pediatric anesthesia is supported
      in several regions. The publications committee supports the distribution of
      textbooks in pediatric anesthesia.

PMID- 19097269
TI  - Special issue in memory of John Newsom-Davis.

PMID- 19097270
TI  - Pediatric Allergy and Immunology. In this issue.

PMID- 19097271
TI  - Allergies to fruits and vegetables.
AB  - Allergic reactions to fruits and vegetables are frequently observed in older
      children and adolescents. They can result from a primary sensitization to food
      allergens or from a primary sensitization to inhalant allergens such as pollens
      or latex. In the case of fruit allergies, the stability of the allergens involved
      is crucial to the sensitization pathway and in the clinical presentation of the
      food allergy. Two patients allergic to fruits are presented and discussed in the
      light of the allergens involved. Patient 1 was a 14 yr-old girl with a grass and
      olive pollen allergy who developed oropharyngeal symptoms typical of the oral
      allergy syndrome (OAS) with multiple fruits from taxonomically unrelated
      families, and who was sensitized to profilin. Patient 2 was an 8 yr-old girl,
      with no pollen allergies, who developed systemic reactions to peach and apple,
      and who was sensitized to non-specific lipid transfer proteins (LTP). Profilins
      are labile allergens present in pollens and foods, and sensitization occurs
      through the respiratory route to pollen profilin. The cross-reactive IgE
      antibodies generated can elicit local reactions in the oropharyngeal mucosa (OAS)
      when exposed to fruit profilins. In contrast, LTPs are a family of stable
      allergens that resist thermal treatment and enzymatic digestion, and can thus
      behave as true food allergens inducing primary (non-pollen related)
      sensitizations and triggering systemic reactions. These two cases represent two
      distinct patterns of sensitization and clinical expression of fruit allergies
      that are determined by the panallergens involved (LTPs and profilins) and their
      intrinsic physicochemical properties. Additionally, these two cases also show the
      improved diagnostic value of Component Resolved Diagnosis, and strengthen its
      utility in the routine diagnosis and management of patients.

PMID- 19097272
TI  - [Anesthesia awareness and the bispectral index].

PMID- 19097273
TI  - Involvement of A2A receptors in anxiolytic, locomotor   and motivational
      properties of ethanol in mice.
AB  - We have shown previously that mice lacking the adenosine A2A receptor (A2AR)
      generated on a CD1 background self-administer more ethanol and exhibit
      hyposensitivity to acute ethanol. We aimed to investigate if the increased
      propensity of A2A(-/-) mice to consume ethanol is associated with an altered
      sensitivity in the motivational properties of ethanol in the conditioned place
      preference (CPP) and conditioned taste aversion (CTA) paradigms and with an
      altered development of sensitization to the locomotor effects of ethanol. We also
      tested their sensitivity to the anxiolytic effects of ethanol. Our results show
      that A2A(-/-) mice produced on a CD1 background displayed a reduced ethanol
      induced CPP and an increased sensitivity to the anxiolytic and locomotorstimulant
      effects of ethanol, but they did not show alteration in ethanol-induced CTA and
      locomotor sensitization. Ethanol-induced CPP, ethanol consumption and the
      locomotor effects of ethanol were also tested in A2A(-/-) mice produced on a
      C57BL/6J background. Our results emphasized the importance of the genetic
      background because alteration in ethanol consumption and preference, ethanol
      induced CPP and locomotor-stimulant effects were not found in knockout mice
      produced on the alcohol-preferring C57BL/6J genetic background. Finally, the A2AR
      agonist, 2-p-(2-carboxyethyl)-phenylethylamino-50-N-ethylcarboxamidoadenosine
      hydrochloride (CGS 21680), reduced ethanol consumption and preference in C57BL/6J
      mice. In conclusion, A2AR deficiency in mice generated on a CD1 background leads
      to high ethanol consumption that is associated with an increased sensitivity to
      the locomotor-stimulant/anxiolytic effects of ethanol and a decrease in ethanol
      induced CPP.

PMID- 19097274
TI  - The right to health: from rhetoric to reality.

PMID- 19097275
TI  - [Automatic detection of perfusion deficits with Bolus Harmonic Imaging].
AB  - PURPOSE: The diagnosis of ischemic stroke relies increasingly on the usage of
      ultrasound-based methods. One of the recent methods is the transcranial, contrast
      agent-based Bolus Harmonic Imaging (BHI) method. The captured image sequence is
      manually examined by clinical experts thus resulting in a time-consuming
      procedure. The purpose of this study is to evaluate three different methods to
      analyze BHI image sequences automatically for the detection of ischemic brain
      tissue. MATERIALS AND METHOD: BHI captures an image sequence that provides
      information on the dynamic behavior of the ultrasound contrast agents. This image
      sequence is analyzed using three different procedures. First a system relying on
      expert knowledge is used to determine perfusion defects. This procedure requires
      parametric images, which are previously extracted from the image sequence. The
      parameter images are then categorized by an unsupervised classification method in
      well-perfused and ischemic tissue by regarding the parametric images as features
      describing the perfusion. Thirdly, the whole image sequence can be interpreted as
      a pixel-by-pixel behavior out of contrast agents. The dynamic curve of each pixel
      can be automatically classified as perfused and ischemic tissue by the K-Means
      method without extracting parametric images. In all three cases a closing step is
      necessary for the accurate interpretation of the results. Transcranial ultrasound
      imaging produces typical stripe artifacts that have to be detected and
      eliminated. A result image is then created and provides a conclusion about
      perfusion reduction in brain tissue. RESULTS: All three methods have been
      validated on the basis of 26 patients by clinical experts. The segmentation on
      the contrast agent kinetics has proven to be most effective. According to our
      patient database, it provides the highest detection accuracy, resulting in a
      sensitivity of 100% and a specificity of 100%. CONCLUSION: The presented methods
      seem to be adequate for detecting ischemic brain tissue. The classification of
      contrast agent kinetics provides the best results and has further advantages. It
      is robust with respect to noise and the calculation is fast because the
      extraction of parametric images is omitted. The very high sensitivity and
      specificity must be validated in a larger patient population. Reliable and
      automated detection of perfusion defects at the bedside seems to be possible.

PMID- 19097276
TI  - Right to health and the Universal Declaration of Human Rights.

PMID- 19097277
TI  - Rights-based approaches to improve people's health in Peru.

PMID- 19097278
TI  - Gender equality and the right to health.

PMID- 19097279
TI  - Why and how is health a human right?

PMID- 19097280
TI  - Health systems and the right to health: an assessment of  194 countries.
AB  - 60 years ago, the Universal Declaration of Human Rights laid the foundations for
      the right to the highest attainable standard of health. This right is central to
      the creation of equitable health systems. We identify some of the right-to health
      features of health systems, such as a comprehensive national health plan, and
      propose 72 indicators that reflect some of these features. We collect globally
      processed data on these indicators for 194 countries and national data for
      Ecuador, Mozambique, Peru, Romania, and Sweden. Globally processed data were not
      available for 18 indicators for any country, suggesting that organisations that
      obtain such data give insufficient attention to the right-to-health features of
      health systems. Where they are available, the indicators show where health
      systems need to be improved to better realise the right to health. We provide
      recommendations for governments, international bodies, civil-society
      organisations, and other institutions and suggest that these indicators and data,
      although not perfect, provide a basis for the monitoring of health systems and
      the progressive realisation of the right to health. Right-to-health features are
      not just good management, justice, or humanitarianism, they are obligations under
      human-rights law.

PMID- 19097281
TI  - Quantitative biology: a new paradigm for tumor profiling, prognosis, and
      treatment.

PMID- 19097288
TI  - The name of the devil.

PMID- 19097282
TI  - Assessing therapeutically developed assays.
AB  - Risk classification of early-stage breast cancer patients by gene expression
      profiling can result in substantial drug cost savings. Economic analyses suggest
      that appropriate use of clinically validated molecular diagnostics offers the
      potential for cost savings and improved patient quality of life.

PMID- 19097289
TI  - Updates on managing acute and chronic pain in primary care practice--optimizing
      pain reduction, minimizing adverse events.

PMID- 19097290
TI  - Green kudos.

PMID- 19097291
TI  - Missing panelist.

PMID- 19097292
TI  - In a new light: state-of-the-art imaging technology advancing research across
      disciplines.

PMID- 19097293
TI  - Connecting globally and locally. Dr. William Cheung (D '81, GD '82), the new
      Chairman of the Board of Overseers.

PMID- 19097294
TI  - Bridging the gaps.
AB  - Through Bridging the Gaps, an internship program that links health-related
      service with interdisciplinary training, Penn Dental Medicine students reach out
      to Philadelphia's neediest neighborhoods--and receive huge rewards in return.

PMID- 19097295
TI  - "Six-month recall dental appointments, for all children, are (un)justifiable".
AB  - Each child is an individual with specific needs, which necessitates a different
      plan of management based on the type of oral disease or disability present. This
      raises a question as to whether the customary fixed six-month recall visits for
      children commonly advocated by dental professionals need to be altered/adjusted
      so as to reflect the individual's oral health needs more closely, in order to
      optimize their clinical and cost-effectiveness. This paper provides a
      comprehensive review of the evidence to either justify or refute the six-month
      recall dental appointments for all children. Based on the available evidence, we
      conclude that the judgment about appropriate intervals should be made by the
      dental practitioner on an individual risk basis as insufficient evidence exists
      to either justify, or refute the six-month recall dental appointments.

PMID- 19097296
TI  - Osteoporosis Part II: prevention and treatment.

PMID- 19097297
TI  - Sinusitis.  How to get relief without antibiotics.

PMID- 19097298
TI  - Food for thought: tomatoes, broccoli, and prostate cancer.

PMID- 19097299
TI  - On call. I am pretty healthy for a 73-year-old, but my cholesterol is 280, and my
      doctor wants me to take Lipitor. I'm willing to do so, but I need to know what
      tests I should have to be sure I'm not getting side effects. What do you suggest?

PMID- 19097300
TI  - Voltage-gated potassium channel Kv1.3 in rabbit ciliary epithelium regulates the
      membrane potential via coupling intracellular calcium.
AB  - BACKGROUND: The cell layer of the ciliary epithelium is responsible for aqueous
      humor secretion and maintenance. Ion channels play an important role in these
      processes. The main aim of this study was to determine whether the well
      characterized members of the Kv1 family (Kv1.3) contribute to the Kv currents in
      ciliary epithelium. METHODS: New Zealand White rabbits were maintained in a 12
      hours light/dark cycle. Ciliary epithelium samples were isolated from the
      rabbits. We used Western blotting and immunocytochemistry to identify the
      expression and location of a voltage-gated potassium channel Kv1.3 in ciliary
      body epithelium. Membrane potential change after adding of Kv1.3 inhibitor
      margatoxin (MgTX) was observed with a fluorescence method. RESULTS: Western
      blotting and immunocytochemical studies showed that the Kv1.3 protein expressed
      in pigment ciliary epithelium and nonpigment ciliary epithelium, however it
      seemed to express more in the apical membrane of the nonpigmented epithelial
      cells. One nmol/L margatoxin, a specific inhibitor of Kv1.3 channels caused
      depolarization of the cultured nonpigmented epithelium (NPE) membrane potential.
      The cytosolic calcium increased after NPE cell depolarization, this increase of
      cytosolic calcium was partially blocked by 12.5 micromol/L dantrolene and 10
      micromol/L nifedipine. These observations suggest that Kv1.3 channels modulate
      ciliary epithelium potential and effect calcium dependent mechanisms. CONCLUSION:
      Kv1.3 channels contribute to K+ efflux at the membrane of rabbit ciliary
      epithelium.

PMID- 19097301
TI  - Note to travellers: prevention of falciparum malaria.

PMID- 19097302
TI  - C-reactive protein levels for early detection of postoperative infection after
      fracture surgery in 787 patients.

PMID- 19097303
TI  - Simvastatin with or without ezetimibe in familial hypercholesterolemia.

PMID- 19097304
TI  - Rosuvastatin in older patients with systolic heart failure.

PMID- 19097305
TI  - Efficacy of cholesterol-lowering therapy with statins in people with diabetes.

PMID- 19097307
TI  - [Age aspects of epidemiology and clinical presentations of tick-borne
      encephalitis].

PMID- 19097308
TI  - [Perinatal pathology of the central nervous system in the genesis of attention
      deficit hyperactivity disorder].

PMID- 19097309
TI  - [Use of anticonvulsant pregabalin as an add-on therapy in patients with partial
      epilepsy with polymorphic seizures].

PMID- 19097310
TI  - [Pharmacoresistance and tolerability in epilepsy].

PMID- 19097311
TI  - [Therapeutic resistance in schizophrenia and biological methods of its
      overcoming].

PMID- 19097312
TI  - [Atomoxetine (strattera) in the treatment of attention deficit hyperactivity
      syndrome].

PMID- 19097313
TI  - [17-year old girl with fever and abscess].

PMID- 19097314
TI  - [Toxic shock syndrome].

PMID- 19097316
TI  - [Lactose- and other intolerance].

PMID- 19097315
TI  - [Efficacy of katadolon and cranial-spine electromagnetic neuromodulation in
      patients with discogenic radiculopathy].

PMID- 19097317
TI  - Response: Mayo Clinic Proceedings' relationship with osteopathic physicians
      misrepresented.

PMID- 19097318
TI  - [Senior policy for physicians in primary health care].

PMID- 19097319
TI  - [Don Juan physicians].

PMID- 19097320
TI  - [Raymond Decary (1891-1973), or Madagascar as seen in collections].

PMID- 19097321
TI  - From pack animals to railways: transport and the expansion of peanut production
      and trade in Senegal, 1840-1940.

PMID- 19097323
TI  - Molecule of the month. The 'skinny' on CB1 antagonists/inverse agonists:
      controversial obesity drugs will not go to FDA for approval.

PMID- 19097322
TI  - [Desire Charnay, or the vestiges of a scientific work].

PMID- 19097324
TI  - Is there evidence of birth control in late Imperial China?

PMID- 19097325
TI  - The prevention of infirm or monstrous births.

PMID- 19097326
TI  - Reading beyond the words: material letters and the process of interpretation.

PMID- 19097327
TI  - Orthopedic surgery.

PMID- 19097328
TI  - Plastic surgery.

PMID- 19097330
TI  - One-health wonders. Interview by R. Scott Nolen.

PMID- 19097329
TI  - Blueprint of the certification examination in cardiovascular computed tomography.
AB  - Physician certification is critical in all areas of cardiovascular imaging to
      assure optimal performance and interpretation of quality studies for patient
      diagnosis and management. This is especially important in the field of
      cardiovascular computed tomography where practitioners have varied training and
      expertise that may not cover the full range of skills in the technical, image
      interpretative and clinical application of the results for patient management.
      The Certification Board of Cardiovascular Computed Tomography was developed to
      test the minimal level of competence of physicians performing cardiovascular
      computed tomography. In this article, the process of defining the content areas,
      determining candidate eligibility and the process of examination development and
      testing will be defined.

PMID- 19097332
TI  - Audiologist.

PMID- 19097331
TI  - Critical care medicine.

PMID- 19097333
TI  - PI3K-Akt signaling and viral infection.
AB  - PI3K-Akt pathway is an important mechanism through which viral infection
      influences various cell functions. Activating PI3K-Akt signaling is a strategy
      employed by viruses to slow down apoptosis and prolong viral replication in both
      acute and persistent infection. It is also probable that prevention of cell death
      facilitates virus-induced carcinogenesis. Accumulating evidence suggests that the
      activity of PI3K or Akt is critical for survival of a few viruses. Adenovirus
      relies on PI3K-mediated organization of actin filament for active
      internalization. Non-segmented negative-sense RNA viruses require Akt to enhance
      synthesis of viral RNAs. On the other hand, PI3K-Akt signaling is associated with
      up-regulating interferon response. Higher PI3K-Akt activity might impede viral
      propagation due to activation of cellular defenses. Influenza A virus is an
      interesting case which requires active PI3K for penetration despite the negative
      effects of inducing immune response. Unlike most viruses, it was reported that
      VP1 protein of foot-and-mouth disease virus inhibits Akt to promote cell death.
      These reports confirm the multiple roles of PI3K-Akt pathway in viral infection.
      Here, more new information on the interaction between PI3K-Akt signaling and
      viral infection is discussed.

PMID- 19097334
TI  - General surgery.

PMID- 19097335
TI  - Cervical artificial disc replacement surgery.

PMID- 19097336
TI  - Are meniscal tears common  among adults >50 years?

PMID- 19097337
TI  - Do inhaled anticholinergics for COPD  increase the risk of cardiovascular
      disease?

PMID- 19097338
TI  - Do combination antipyretics work faster  than ibuprofen alone in children?

PMID- 19097339
TI  - Is aspirin plus dipyridamole as effective  as clopidogrel for preventing
      recurrent  stroke?

PMID- 19097340
TI  - Patient handout. Managing chronic pain: your personal care plan.

PMID- 19097341
TI  - Atelectasis during anesthesia: physiology and treatment.

PMID- 19097342
TI  - Is it too much to ask...help the doctor.

PMID- 19097343
TI  - Effect of breastfeeding education and support on promoting breastfeeding: a
      literature review.
AB  - Despite the widely documented benefits of breastfeeding, initiation rates and
      duration of breastfeeding lag behind the goals set in Healthy People 2010. This
      paper evaluates the effectiveness of breastfeeding education and support, which
      aim to encourage women to initiate and continue breastfeeding according to The
      Healthy People 2010 objectives; articles published in the United States from
      January 2000 to July 2005 are included. Effects of these interventions on
      different demographic groups are reviewed to assess the importance of each
      intervention in particular focus group.

PMID- 19097344
TI  - Mollaret's meningitis caused by herpes simplex virus type 2: case report and
      review of literature.

PMID- 19097345
TI  - Care management benefits physicians, SoonerCare members.

PMID- 19097346
TI  - Shortcomings of continuing medical education.

PMID- 19097347
TI  - Who's in charge?

PMID- 19097348
TI  - The uninsured, will they always be with us?

PMID- 19097349
TI  - Discounts to needy patients.

PMID- 19097350
TI  - Supervising retail clinic personnel: the TMA adopts guidelines for members.

PMID- 19097351
TI  - Case settled, liability accepted; why?

PMID- 19097352
TI  - From data interoperability to value-driven healthcare.

PMID- 19097353
TI  - ST segment elevation in lead aVR: what to expect from this orphan?
AB  - Standard 12-lead electrocardiography is used to diagnose acute myocardial
      infarctions in patient presenting with ST elevation. The specificity of ST
      segment elevation for the corresponding area is more than 90 percent. It has been
      suggested that ST-segment elevation in lead aVR may indicate left main disease.
      We will present a patient who had an ST segment elevation in this lead. We will
      review the current data about this finding, as well as the significance of ST
      segment elevation in other leads.

PMID- 19097354
TI  - Medical battery claims present unique challenges in court.

PMID- 19097355
TI  - Usefulness of immunohistochemistry in identification of prognostically important
      subgroups (GCB and ABC) in a heterogeneous group of diffuse large B-cell
      lymphomas--a review article.
AB  - Although diffuse large B cell lymphomas (DLBCL) are considered in the WHO
      classification a specific histopathological type, their diversity in the clinical
      features, morphology and molecular aberrations strongly suggest that these tumors
      represent a heterogeneous group of neoplasms rather than a single
      clinicopathological entity. There have been various approaches to differentiate
      between separate nosological entities within DLBCLs based on various methods,
      such as the microarray technique or immunohistochemistry. Although it has been
      proven that gene expression profiling using cDNA microarrays could identify
      prognostically important subgroup of DLBCL: germinal center B-cell (GCB)-like
      DLBCL and activated B-cell (ABC)-like DLBCL, this method is impractical as a
      clinical tool. Therefore, investigators have started using immunohistochemistry
      in their studies. Employing various immunohistochemical antibodies, such as CD10,
      CD138, anti-Bcl-2, anti-Bcl-6, MUM1 and anti-p53, several groups have aimed at
      subclassifying DLBCL into the GCB and ABC subgroups with comparable differences
      in clinical behavior. This review summarizes these data and indicates their
      impact on DLBCL classification.

PMID- 19097356
TI  - Pathology of renal tumors in adults. Molecular biology, histopathological
      diagnosis and prognosis.
AB  - Malignant renal tumors constitute 3% of human cancers, although their frequency
      differs greatly in various areas. Since the fifties, the incidence of renal
      cancers has been increasing, but at the some time the prognosis has been
      improving. In particular, in the last years, several new treatment modalities
      have been introduced, relying on the understanding of renal cancer biology. The
      identified etiological factors include smoking, increased body mass, dietary
      factors and chronic renal disease. There are several renal tumor types differing
      in morphology, molecular genetics and biology. Inactivation of the VHL gene leads
      to formation of the most frequent form in adults, namely clear cell carcinoma.
      The VHL gene product, a component of an ubiquitin-ligase complex, regulates
      expression of several genes. Papillary carcinomas depend mainly on the HGF
      receptor gene (c-Met) activating mutations. At least two types of papillary
      carcinomas exist, which have different morphology and prognosis. The molecular
      biology of chromophobe carcinoma and oncocytoma is poorly understood.
      Differential diagnosis of these tumors is particularly difficult and may require
      extensive immunohistochemical and molecular studies. Collecting duct carcinoma
      and medullary carcinoma are extremely aggressive but rare tumors. Some renal
      tumors have been described or recognized only relatively recently; these newer
      entities include multilocular cystic clear cell carcinoma, spindle cell papillary
      mucinous carcinoma, tubulocystic carcinoma, renal epithelial and stromal tumor,
      epithelioid and oncocytic angiomyolipoma. Besides histological typing, the
      prognostic factors include tumor stage, grade and several immunohistochemical and
      molecular markers that are currently under elaboration. The improved prognosis in
      renal cancer depends on earlier detection, but also on refinement of therapeutic
      methods. Small tumors may currently be treated by partial nephrectomy or
      radiofrequency ablation and larger ones by a laparoscopic approach. All these
      methods seem to give satisfactory results with low morbidity and mortality rates.
      Renal carcinoma is notorious for its low sensitivity to chemotherapy and
      radiotherapy. For several years, immunological treatment with IL-2 and INF-alpha
      was the only adjuvant therapy method. However, recently several new drugs have
      been introduced; they act on tyrosine-kinase receptors, VEGF, c-Met or mTOR
      pathway. With this progress, perfect understanding of renal tumor biology and
      exact histological diagnosis have become of prime practical importance.

PMID- 19097357
TI  - Examination of expression of WT1 gene product and CD44 adhesive molecule in
      nephroblastoma histologic types.
AB  - In spite of success of modern pediatric oncology, cases in which we are not able
      to reach the prospective affirmative effect of performed therapy are still
      observed. The purpose of our study was to examine the expression of WT1 gene
      product and CD44 adhesive molecule in nephroblastoma histologic types - one of
      the currently used prognostic marker for this group of tumor. We found
      correlations between CD44 expression and histologic type of tumor. We suppose
      that high CD44 expression in nephroblastoma group of tumors may confirm their
      high malignant potential. Expression of the WT1 gene product we found in all the
      investigated tumor tissue samples. However we did not found statistically
      significant correlations between WT1 expression and histologic type of the tumor
      and there was no correlation between CD44 and WT1 expression in blastemal nor of
      epithelial component of nephroblastoma in our study. Lack of this correlation
      also permits to suppose that the high activity is an integral feature of all
      Wilms tumor cells and is not only characteristic for anaplastic and blastemal
      nephroblastomas.

PMID- 19097358
TI  - Colon invasive micropapillary carcinoma arising in tubulovillous adenoma.
AB  - Invasive micropapillary carcinoma (IMPC) is defined as a carcinoma composed of
      small clusters of tumor cells lying within clear spaces which simulate
      lymphovascular channels. This histologic pattern has been described in various
      organs, including the breast, lung, urinary bladder, ovary, stomach, pancreas,
      and major salivary glands. Although rarely observed as a pure histologic
      component, IMPC is usually mixed with conventional carcinoma, and is therefore
      often referred to as carcinoma with a micropapillary component. IMPCs are
      invariably associated with a high degree of aggressiveness, extensive
      lymphovascular invasion, extensive lymph node metastases, and poor prognosis. I
      herein describe a case of primary IMPC originating in colon polyp as a minor
      histologic component.

PMID- 19097359
TI  - [Galectins in squamous cell carcinomas of the head and neck cancers].
AB  - Cancers of head and neck represents about 5% of all tumors. 80 to 90% of these
      tumors are constituted of squamous cell carcinomas. Despite a rapid progress in
      diagnostics and therapy the overall 5-year survival of this type of cancer is
      among the lowest of the major cancer types. This unfavourable situation needs the
      extensive research to found new markers to better characterize biological
      behavior of tumors as a rational background for more sophisticated therapeutic
      modalities. Among the most promising markers are endogenous lectins called
      galectins and their ligands. Especially galectin-1, -3 and -7 play a key role in
      pathology of squamous cell carcinomas.

PMID- 19097360
TI  - Hiatal hernia and Barrett's oesophagus impact on symptoms occurrence and
      complications.
AB  - The aim of the study was to evaluate the influence of sliding hiatal hernia over
      the Barrett's oesophagus, including symptoms rate and complications. METHODS: A
      total of 520 (4.6%) cases of Barrett's oesophagus were found out of 18.276 upper
      gastrointestinal endoscopies, performed in 11.276 patients at a single tertiary
      centre in a period from 1994 to 2004. RESULTS: Sliding hiatal hernia was found in
      58% of patients with Barrett's oesophagus, more frequently in men (60%). The
      association between hernia and some complications of Barrett's oesophagus was
      significant (94% of Barrett's ulcer, 77% of low-grade dysplasia with p < 0.01).
      However, there was no significant association with adenocarcinoma (54%; p >
      0.05). The other complications of Barrett's oesophagus (i.e. bleeding, stenosis,
      high-grade dysplasia) were identified in small number (less than 10), so they
      were not evaluated statistically. Association between the presence of hiatal
      hernia and occurrence of symptoms (reflux symptoms, dysphagia, odynophagia,
      dyspeptic and other symptoms) was significant with p < 0.01. CONCLUSIONS: Our
      study suggests that sliding hiatal hernia may play a significant role as a
      pathophysiologic factor in Barrett's oesophagus. Complications rate of Barrett's
      oesophagus were not equally frequent in particular cases with hiatal hernia. The
      occurrence of symptoms is getting more pronounced in those with sliding hiatal
      hernia.

PMID- 19097361
TI  - Primary B-cell pituitary lymphoma of the Burkitt type: case report of the rare
      clinic entity with typical clinical presentation.
AB  - Primary CNS lymphomas (PCNSLs) constitute 3% of all intracranial neoplasms. From
      these, primary pituitary lymphomas (PPLs) represent extremely rare clinical
      entity. Nearly all of PCNSLs are non-Hodgkin diffuse large B-cell lymphomas. We
      present a 60-year-old female with right-sided third cranial nerve palsy, mild
      bitemporal visual field deficit, severe cephalea, and polyuria-polydipsia.
      Hypopituitarism with hyperprolactinemia was confirmed; brain imaging revealed a
      16 mm-diameter sellar mass with suprasellar extension. A presumptive diagnosis of
      pituitary adenoma was established. The patient underwent a neurosurgical
      intervention. Histopathological examination and immunophenotyping (cytokeratin,
      CD45+, CD79+, bcl-2-) verified high-grade B-cell non-Hodgkin lymphoma of the
      Burkitt type. Systemic work-up showed no other foci of lymphoma, the patient's
      HIV status was negative, Epstein-Barr virus status was not disclosed. Although
      PPL can be undistinguishable from pituitary adenoma at imaging, one should
      consider lymphoma when evaluating an invasive sellar mass that is iso- to
      hypointense on T2-weighted magnetic resonance images, particularly when the
      patient is immunocompromised or old and presents with diabetes insipidus, cranial
      nerve palsy and fever of unknown origin in addition to the expected finding of
      hypopituitarism.

PMID- 19097362
TI  - [Pathogenetically complicated case of osteoporosis in a young man].
AB  - Osteoporosis, is a serious disease both in women and men, with a high risk of
      fractures. However, its pathogenesis differs markedly, with the secondary form
      being more common in men. The aim of this case study is to demonstrate the
      complex pathogenesis of a severe osteoporosis in a 23-year-old heavy smoker with
      histiocytosis X, diabetes insipidus (DI), subclinical hypogonadism and low serum
      levels of IGF-I. Later, after normalization of sex hormones and IGF-I levels,
      vasopressin substitution, cessation of smoking and after long-term antiresorption
      therapy, adequate increase in bone density at the hip was documented, but
      insufficient and very slow increase at the lumbar spine was observed. Severe
      osteoporosis at the spine is most probably the consequence of the interaction of
      smoking with multiple hormone insufficiency during development of peak bone mass.
      The effect of additional, unidentified factor(s) (gene or hormone) is also
      likely. On the other hand, a direct causal association between histiocytosis X
      and osteoporosis was not confirmed histomorphometrically in this patient.

PMID- 19097363
TI  - [Accompanying document to autopsy at forensic medicine department].

PMID- 19097364
TI  - [From the history of Jubilee Pavilion at the general hospital in Prague].

PMID- 19097365
TI  - [Rationality and irrationality in the medicine and in the life].
AB  - The spiritual life of man has a rational and irrational component. Both have
      positive as well as negative effects and under normal circumstances they are well
      balanced. In medicine rationality is an essential feature of the medical science
      and the basis of medical practice but it is not sufficient for fulfilling all
      curative needs. In the practice, gaps in knowledge must be complemented by
      empiricism and empathy which originate in the personality of the physician.

PMID- 19097366
TI  - [Virusology at the begining of the XXI century].
AB  - Viral injections are the most common human diseases (especiaily acute respiratory
      infections, mostly in children and young adults). The current studies show that
      viral infections can cause not only acute, but persistent viral diseases as well.
      A certain number of viruses are able to incorporate their nucleic acid into the
      genome of the host-cell, leading to rearrangement of the cell genes and formation
      of malignant tumors. Viral persistence can cause manifiestations of latent or
      chronic infections, as well as prion-caused slow infections of the central
      nervous system. Defective Di particles play an important role in maintaining
      viral persistence. Viruses are important agents involved in various disorders of
      the immunological homeostasis of the organism. Newly-found viruses represent a
      special problem.

PMID- 19097367
TI  - [Cyclopentolate as a cycloplegic drug in determination of refractive error].
AB  - Cycloplegia is loss of the power of accommodation with inhibition of a ciliary
      muscle. We obtain in this way the smallest refraction of the lens and make it
      possible to determine the presence and size of the particular refractive error in
      cycloplegia by using cyclopentolate. Cyclopentolate is a synthetic
      anticholinergic drug and antagonist of the muscarine receptors. If applied in the
      eye, it blocks the effect of cholinergic stimulation on the sphincter pupillae
      muscle and ciliary muscle. It provokes severe mydriasis (dilation of the pupil)
      and cycloplegia (paralysis of the accommodation). Cyclopentolate has been used
      occasionaly in diagnostic purposes: defining ocular refraction and in
      ophthalmoscopy. This is the prospective study which included 200 children (400
      eyes) aged 3-18 years, carried out in one ambulatory ophthalmological
      examination. The results were analysed using standard statistical methods. The
      most often refractive error in the examined group of children is hyperopia with
      hyperopic astigmatism, then myopia with myopic astigmatism and mixtus astigmatism
      are the most often in the oldest group of children. The mean value of corneal
      astigmatism on the right eye was 1.24 D, on the left eye 1.23 D. Anisometropy was
      found in 40% children. The presence of myopia, myopic and astigmatism mixtus
      tended to increase, and hyperopia and hyperopic astigmatism tended to decrease
      toward older groups of children. Refractive error could result in a poor
      development of visual acuity, causing amblyopia and strabismus, and because of
      that represents an important public health problem. As one of amblyogenic risk
      factors in children, it can be prevented with screening program and appropriate
      treatment, thus providing prevention of amblyopia as one form of blindness.

PMID- 19097368
TI  - Autoantibodies in patients treated for active pulmonary tuberculosis.
AB  - The genesis of auto-immune antibodies directed against the own tissue antigens of
      a host may be due to the host's immune response to mycobacteria. The prospective
      study included 110 patients treated for active pulmonary tuberculosis and the
      control group of 60 healthy subjects, volontary blood donors. Applying the method
      of indirect immnunofluorescence and cryostat sections of rat organs and human
      larynx cancer epithelial cell line (HEp-2 cells), the prescence of the following
      autoantibodies in the serum of the examined patients was examined: anti,nclear
      (ANA), anticardiac (ACA), antimitochondrial (AMA), antiparietal (APA), anti
      smooth muscular (ASMA), antithyroidal (ATA), rheumnatoid factor (RF). These
      autoantibodies were determined in the course oftreatment and five years later.
      Low levels of some examined autoantibodies were detected in the serum of a number
      of the examined patients. No significant difference in the presence of the
      analysed antibodies was registered between the sexes. In the course of the
      treatment a reversible hyper-gammaglobulinemia developed, which was at least
      partially due to the presence of autoantibodies in the patients blood serum.
      Besides possibly involved mechanisms of molecular mimicry and polyclonal
      lymphocyte activation, the presence of antinuclear antibodies in the patient's
      serum is at least partially due to isoniazide treatment. The finding of other
      autoantibodies is nonspecific and not related to the mycobacterial infection or
      antituberculosis drug administration.

PMID- 19097369
TI  - [Gender as a key effect modifier of the relationship between physician work
      stressors and the acquired cardiovascular disorders].
AB  - To assess gender as an effect-modifier vis-a-vis exposure to work stressors and
      the acquired cardiovascular disorders (ACVDC). METHOD: The Occupational Stress
      Index for physicians was used in a case-control study (>90% participation rate)
      among physicians in Novi Sad (Cases: 50 males and 51 females with ACVD,
      Referents: 46 males and 6l females without ACVD). RESULTS: Patterns of disease
      manifestation, sociodemography, risk factors, Minnesota Multiphasic Personality
      Inventory (MMPI) tendency and exposure to work stressors differed in male
      compared to female physicians with ACVD. Accounting for these covariates, the
      males with ACVD had significantly higher general-level threat avoidance vigilance
      scores (more witnessed accidents at work and expert-witnessing in court (p <
      0.0l)). Female physicians with ACVD had higher general-level underload (more
      fixed pay) and strictness (more limited decision-making concerning work-schedules
      and institutional policies) (p < 0.05). In stratified analysis, the relationship
      between working conditions and ACVD was most apparent among the women physicians.
      Compared to those without ACVD, female physicians with ACVD showed higher
      extrinsic time-pressure (speed-up (p < 0.01)), threat of job loss (p < 0.05), and
      elements of high demand (heterogeneous information, complex and heterogeneous
      task performance) (p < 0.05)), after accounting for covariates. Females in the
      surgical care specialties with ACVD were exposed to significantly higher demands,
      speed-up, and need for constant high attention than their female colleagues
      without ACVD, after accounting for covariates. CONCLUSION: Gender is a key effect
      modifier of the relationship between exposure to work stressors and ACVD among
      physicians. Intervention studies should consider gender-specific work stressors,
      as well as those specific to physicians.

PMID- 19097370
TI  - [Infant biochemical and clinical parameters within the baby friendly programme].
AB  - INTRODUCTION: Breastfeeding is the best nourishing method for the health
      protection, child's growth and development with greatly reduced risks for acute
      and chronic disorders. The first hours after the childbirth are the most
      important. The objective of the research. The objective of the research is to
      establish whether the baby friendly programme affects the infants' biochemical
      and clinical parameters during the first days of their lives. MATERIALS AND
      METHODS: The research was conducted on 216 infants in both groups. The tests on
      glycaemia were done in both groups on 65 infants, tests on bilirubinemia on 75,
      and tests on temperature, stomatomycosis and weight loss tests during the first
      three days in all infants. RESULTS: Hypoglycaemia, hypothermia, significant
      weight loss during the first days and stomatomycosis were observed with the
      significantly high possibility in the infant group outside the baby friendly
      programme, and bilirubinemia did not depend on the programme. DISCUSSION:
      Frequent breastfeeding reduces the starvation periods and the need for
      involvement of alternative metabolic courses in the process of glucose
      homeostasis preservance, and the less frequent cooling of the infant as well, it
      can affect the prevention of hyperbilirubinemia, practically eliminate
      stomatomycosis and lead to less weight loss during the first days of life.
      CONCLUSION: Implementation of the baby friendly programme has the positive effect
      on the glycaemia level and cooling, it does not affect bilirubinemia, its results
      can be seen in less weight loss and in elimination of stomatomycosis.

PMID- 19097371
TI  - [Impact of inaccuracy of peak flowmeters with Wright scale on asthma severity
      assessment in children].
AB  - INTRODUCTION: Measurement of daily variability of peak expiratory flow (PEF) is
      widely accepted as an objective method to assess asthma severity. Recent
      investigations have proved nonlinearity of original Wright scale of peak
      flowmeter. All country members of European Union have been obliged to implement a
      new scale according to standard EN 13826 since 2005. This study examined whether
      the correction of PEF values for the inaccuracy of the scale would affect asthma
      management based on their daily variability. MATERIAL AND METHODS: We analyzed
      PEF values (2352) in 34 children, aged 5-16, during 3-5 weeks of monitoring in
      order to establish the diagnosis of asthma by using peak flowmeters with Write
      scale. The correction of measured values for inaccuracy was managed with original
      Dr. M. Miller's predictive equation. The daily variability of PEF (amplitude
      percent mean) up to 20% was considered as "normal", 20-29.9% as "raised", and 30%
      and above as "high ". The assessment of daily variability was performed before
      and after correction. RESULTS: There was no significant change in the number of
      days with airway lability as regarding the assessed whole study group (p =
      0.475). However, 22 (64.7%) of children had at least one false clinical message
      about daily variability during the monitoring. It was overestimated in 12 (7%)
      days in younger (6.6 +/- 0.8 years) or of shorter stature (122.6 +/- 3.6 cm) and
      underestimated in 13 (4%) days in older (11.1 +/- 2.7) or taller ones (150.9 +/-
      12.5 cm) (p < 0.001). CONCLUSION: Usage of peak flowmeters with Wright scale may
      lead to an error in asthma severity assessment based on daily variability of PEF.
      It may cause overtreatment or undertreatment of asthmatic children.

PMID- 19097372
TI  - [Multi-factoriality of dentine hypersensitivity].
AB  - INTRODUCTION: Dentine hypersensitivity has been defined as a sharp, short pain
      arising from exposed dentin in response to stimuli typically thermal, evaporative
      tactile, osmoticor, chemical and which cannot be ascribed to any other form of
      dental defect or pathology. PREVALENCE: The most affected patients range in age
      from 20 to 40. The following teeth tend to be most sensitive: cuspids, premnolars
      and incisors, location-concentrated on the facial surface. MORPHOLOGICAL BASES OF
      DENTINE HYPERSENSITIVITY: Sensitive teeth have much greater numbers of open
      tubules per unit area and the average diameter of tubules is almost 2 times
      greater than tubules in nonsensitive teeth. MECHANISMS OF DENTINE
      HYPERSENSITIVITY: The most widely accepted theory of how the pain occurs is
      Brannstroms theory. ETIOLOGY: Dentine hypersensitivity represents a condition of
      presumable multifactorial pathology. Two processes are essential for its
      development: (1) dentin must be exposed through either genetic disturbance,
      enamel defect (lamellae, tufs and spindles), loss of enamel (erosion, abrasion,
      attrition, abfraction), gingival recession with rapid loss of cementum and (2)
      the dentin tubules must be open to both the oral cavity and the pulp. DIAGNOSIS:
      Diagnostic protocol for this condition consisted of Medical, Dental Dietary, Oral
      Hygiene History and Inra-oral examinations with air indexing method. Differential
      Dianosis: We must take into consideration a numnber of variables such as: dental
      caries, cracked tooth, restorative sensitivity, medication sensitivity, bleaching
      sensitivity and abscessed or non-vital tooth. CONCLUSION: Dentin hypersensitivity
      is a problem that bothers many patients. Many conditions share the symptoms of
      tooth sensitivity so differential diagnosis is essential for suitable treatment
      or preventive measures.

PMID- 19097373
TI  - [Etiology and pathogenesis of precancerous lesions and invasive cervical
      carcinoma].
AB  - Cervical cancer is the second most common gynecological malignancy in the world.
      Human papilloma virus (HPV) infection is the leading ethiologic agent in the
      development of premalignant and malignant cervical diseases. HPV is a member of
      the Papovaviridae family and until now over 100 types have been recognized There
      are two types of viral infection: latent and productive. Virus induced
      oncogenesis is the result of interaction between virus oncoproteins E6 and E7 and
      tumor supresor host genes p53 and Rb. Many cofactors such as immunosuppression,
      early sexual relationship, multiple sexual partners, other sexualy transsmited
      infections and smoking are contributing factors of the precancerous and invasive
      cervical lesions. According to the oncogenic potential HPV are divided into three
      groups: low, intermediate and high oncogenic risk viruses. Molecular technics
      which are used for the virus detection are: In situ hibridisation, Hyybrid
      capture test and polymerasa chain reaction. Human papilloma virus testing has an
      important role in the follow up and treatment of women with "atypical squamous
      cells of unknown significant" changes in cervical smears and low-grade squamous
      intraepithelial lesions, changes in punch biopsy.

PMID- 19097374
TI  - [Left ventricular hypertrophy in patients treated with regular hemodialyses].
AB  - Left ventricular hypertrophy is the main risk factor for development of
      cardiovascular morbidity and mortality in patients on hemodialysis. Left
      ventricular hypertrophy is found in 75% of the patients treated with
      hemodialysis. Risk factors for left ventricular hypertrophy in patients on
      hemodialysis include: blood flow through arterial-venous fistula, anemia,
      hypertension, increased extracellular fluid volume, oxidative stress,
      microinflammation, hyperhomocysteinemia, secondary hyperparathyroidism, and
      disturbed calcium and phosphate homeostasis. Left ventricular pressure overload
      leads to parallel placement of new sarcomeres and development of concentric
      hypertrophy of left ventricle. Left ventricular hypertrophy advances in two
      stages. In the stage of adaptation, left ventricular hypertrophy occurs as a
      response to increased tension stress of the left ventricular wall and its action
      is protective. When volume and pressure overload the left ventricle chronically
      and without control, adaptive hypertrophy becomes maladaptive hypertrophy of the
      left ventricle, where myocytes are lost, systolic function is deranged and heart
      insufficiency is developed. Left ventricular mass index-LVMi greater than 131
      g/m2 in men and greater than 100 g/m2 in women, and relative wall thickness of
      the left ventricle above 0.45 indicate concentric hypertrophy of the left
      ventricle. Eccentric hypertrophy of the left ventricle is defined
      echocardiographically as LVMi above 131 g/m2 in men and greater than 100 g/m2 in
      women, with RWT ?0.45. Identification of patients with increased risk for
      development of left ventricular hypertrophy and application of appropriate
      therapy to attain target values of risk factors lead to regression of left
      ventricular hypertrophy, reduced cardiovascular morbidity and mortality rates and
      improved quality of life in patients treated with regular hemodialyses.

PMID- 19097375
TI  - Cardiac perioperative complications in noncardiac surgery.
AB  - Anesthesiologists are confronted with an increasing population of patients
      undergoing noncardiac surgery who are at risk for cardiac complications in the
      perioperative period. Perioperative cardiac complications are responsible for
      significant mortality and morbidity. The aim of the present study was to
      determine the incidence of perioperative (operative and postoperative) cardiac
      complications and correlations between the incidence of perioperative cardiac
      complications and type of surgical procedure, age, presence of concurrent
      deseases. A total of 100 patients with cardiac diseases undergoing noncardiac
      surgery were included in the prospective study (Group A 50 patients undergoing
      intraperitoneal surgery and Group B 50 patients undergoing breast and thyroid
      surgery). The patients were followed up during the perioperative period and after
      surgery until leaving hospital to assess the occurrence of cardiac events.
      Cardiac complications (systemic arterial hypertension, systemic arterial
      hypotension, abnormalities of cardiac conduction and cardiac rhythm,
      perioperative myocardial ischemia and acute myocardial infarction) occurred in
      64% of the patients. One of the 100 patients (1%) had postoperative myocardial
      infarction which was fatal. Systemic arterial hypertension occured in 57% of
      patients intraoperatively and 33% postoperatively, abnormalities of cardiac
      rhythm in 31% of patients intraoperatively and 17% postoperatively, perioperative
      myocardial ischemia in 23% of patients intraoperatively and 11% of
      postoperatively. The most often cardiac complications were systemic arterial
      hypertension, abnormalities of cardiac rhythm and perioperative mvocardial
      ischemia. Factors independently associated with the incidence of cardiac
      complications included the type of surgical procedure, advanced age, duration of
      anaesthesia and surgery, abnormal preoperative electrocardiogram, abnormal
      preoperative chest radiography and diabetes.

PMID- 19097376
TI  - [Psychosomatic concept of hyperthyroidism-Graves type--behavioral and biochemical
      characteristics].
AB  - INTRODUCTION: In this study we test the hypothesis that specific behavioral and
      biochemical vulnerabilities characterize individuals with hyperthyroidism-Graves
      type, one of the classically cited "psychosomatic disorders". MATERIAL AND
      METHODS: The sample included 24 subjects with Graves disease and 34 controls. All
      participants were evaluated for personality and temperament characteristics and
      for platelet MAO activity. A smaller group of panic disorder patients was tested
      with the same set of measures to ensure a validity of the study, especially
      regarding results on personality tests. RESULTS: Individuals with hyperthyroidism
      had lower platelet MAO activity and higher scores on histrionic (Hy), depressive
      (D) and hypochondriac (H) subscale on the MMPI-201 than normal controls. Their
      TPQ temperament scores were characterized by high Harm Avoidance, whereas other
      temperament traits were average. Platelet MAO activity was inversely correlated
      with the MMPI-201 psychopatic deviance scale (Pd) and positively correlated with
      the TPQ Reward Dependence scale. CONCLUSIONS: Our results provide support for the
      psychosomatic concept of Graves' disease. Personality features, temperament
      traits, and platelet MAO activity of hyperthyroid individuals are different from
      those in normal controls and correspond to those observed in anxiety disorders.
      We propose that the observed behavioral and biochemical similaritites between
      hyperthyroid and anxiety disorder patients represent an equicausality phenomenon,
      where the same underlying heritable factors, such as variable central
      monoaminergic activity coupled with temperament-related susceptibility to stress,
      facilitate phenotypic manifestation of a number of psychosomatic and psychialric
      disorders--including Graves disease. The observed correlations between
      personality traits and MAO activity provide support for the hypothesized
      functional relationship between the underlying central monoaminergic activity and
      temperament traits associated with anxiety, depression, and impulsivity.

PMID- 19097377
TI  - [The role of holotranscobalamin in examination of vitamin B12 status].
AB  - INTRODUCTION: Holotranscobalamin contains biologically available cobalamin
      because only holotranscobalamin promotes the uptake of the cobalamin therein by
      all cells, via specific receptors. Therefore holotranscobalamin has been proposed
      as a potentially useful alternative indicator of vitamin B12 status. The aim of
      the present study was to assess usefulness of holotranscobalamin in the
      evaluation of vitamin B12 status. MATERIAL AND METHODS: We examined serum level
      of holotranscobalamin in 135 subjects divided in four groups according to the
      serum concentration of vitamin B12: 30 subjects with vitamin B12 <154 pmol/l, 50
      subjects with vitamin B12 154-250, 30 subjects with vitamin B12 2251-350 pmol/l,
      25 subjects with vitamin B12 >350 pmol/l. RESULTS: The results show that in
      subjects with low vitamin B12 serum level there are those with normal
      holotranscobalamin concentration (60%) and that in subjects with normal vitamin
      B12 there are those with low holotranscobalamin concentration (22%). The obtained
      results also show positive significant correlation between levels of
      holotranscobalamin and vitamin B12 (r = 0.62, p < -0.001). CONCLUSION: We can
      conclude that biologically active cobalamin, holotranscobalamin, is a useful tool
      when examining vitamin B12 status especially in subjects with borderline and low
      vitamin B12 concentrations. Measurements of the serum holotranscobalamin may be
      superior to total serum cobalamin.

PMID- 19097378
TI  - [Serum calcium and phosphorus concentration and alkaline phosphatase activity in
      healthy children during growth and development].
AB  - INTRODUCTION: Many changes happen during growth and development in an organism as
      a result of important hormon changes, especially biohumoral ones. These changes
      make a problem when interpreting biochemical results in pediatric population. The
      most important changes are intensive calcium and phosphorus metabolic turnover in
      bone tissue with changes in alkaline phosphatase activity as a result of
      osteoblast activity. The aim of this study was to follow the serum calcium and
      phosphorus concentration and alkaline phosphatase activity in children 1-15 years
      old in different growth and development period and of different sexes and to
      fortify the influence of growth and development dynamics on biohumoral status in
      healthy male and female children. MATERIAL AND METHODS: We evaluated 117 healthy
      children of both sexes from 1-15 years of age and divided them into three age
      groups: 1-5, 6-10 and 11-15 years. We followed the serum calcium and phosphorus
      concentration and alkaline phosphatase activity in different groups and in
      different sexes. RESULTS AND CONCLUSION: Our investigation found significantly
      higher values of serum calcium in boys than in girls with no important changes
      between the age groups and significantly higher values of serum phosphorus in the
      youngest age group in all children and in different sexes with no important sex
      differences. Alkaline phosphatase activity followed the growth spurt and was the
      biggest in 6-10 years group in girls and in 11-15 years group in boys.

PMID- 19097379
TI  - [Results of kidney function measurement and blood pressure in population from
      endemic region of Vitina].
AB  - INTRODUCTION: The analysis of frequency of kidney diseases, causes of terminal
      renal failure in patients subjected to repeated dialysis in major dialysis
      centers in the region of Kosovo and Metohija as well as mortality rate in these
      patients showed a stable number of patients with kidney diseases, evidencing that
      the populations of Vitina and Gnjilane were the most commonly affected These
      towns are designated as regions with the highest incidence of Balkan endemic
      nephropathy. The present analysis was aimed at: (1) establishing the incidence
      rate of hypertension and renal function impairment by using clinical and
      laboratory analyses in individuals from Vitina and neighboring villages, and (2)
      investigating the correlation between creatinine clearance, age and arterial
      blood pressure in the studied group. MATERIAL AND METHODS: The analysis included
      510 individuals (excluding diabetics) over the one-month period during 2004 (201
      males with their age ranging from 18 to 90 years). Blood pressure measurements
      were performed in all the individuals, while renal function was determined by
      glomerular filtration rate (GFR), as calculated according to Cockcroft-Gault
      formula. RESULTS: Creatinine clearance was lower than 100 ml/min in 237 (46.5%)
      individuals, out of whom 62 (12%) had GFR below 60 ml/min. Among the remaining
      273 (53.5%) individuals with GFR above 100 ml/min, 68 individuals had GFR above
      140 ml/min. The distribution of patients depending on their systolic blood
      pressure values revealed that systolic blood pressure was lower in 44 subjects
      and higher in 302 subjects (59%). The correlation test revealed significant
      association between the studied parameters. The positive correlation between
      patients' age and kidney function means the higher the age of subjects the lower
      creatinine clearance value (r = --0.622, p < 0.001). The negative correlation of
      the systolic blood pressure value and kidney function was found, meaning that
      higher the systolic blood pressure is accompanied by lower creatinine clearance
      (r = --0.204, p < 0.001). Moreover, patients' age was significantly correlated
      with the systolic blood pressure level (r = 0.511, p < 0.001), as well as with
      the diastolic blood pressure level (r = 0.299, p < 0.001). The former means that
      higher values of both systolic and the diastolic pressures were found in older
      subjects. No correlation was found between the diastolic blood pressure level and
      kidney function (the results are not presented). Conclusion The results obtained
      in the study confirm significant incidence of renal function impairment measured
      according to creatinine clearance values in patients from the endemic nephropathy
      region. Reduced kidney function is found in both elderly individuals and those
      with high systolic blood pressure. In order to establish the correlation with the
      incidence and presence of BEN or other kidney diseases additional population
      screening is necessary.

PMID- 19097380
TI  - [Viral form of hemophagocytic syndrome with erythrodermal clinical picture--case
      report].
AB  - INTRODUCTION: Hemophagocytic syndrome is patophysiological entity with
      proliferation and over-activation of macrophages, with hemophagocytosis and
      production of proinflammatory cytokines. It arises as hereditary forms, or
      acquired, during viral, autoimmune or malignant diseases, and is usually a
      disorder with fulminant course and high incidence of lethal outcome. The precise
      mechanism is not resolved; it is a consequence of cytokine storm generated by
      over-activated T cells and macrophages, due to defects in T cellular cytototoxic
      function and inadequate down-regulation of immune response. CASE REPORT: A male
      patient, 26 years old, previously healthy, is presented. Generalized exfoliative
      dermatitis and lymphadenomegalia had lasted for half a year before admission to
      the hospital. Hemophagocytosis in lymph gland histology was diagnostic, with T
      cellular immunohistochemical profile CD3+, CD5-, CD8/-, CD43+/-, CD45RO+, bcl-2+,
      and numerous CD68+ histiocytes. Apart from elevated titer of Adenovirus serology,
      other laboratory findings and bone marrow histology were within normal limits.
      Two weeks of oral antibiotic and topical skin corticosteroid therapy were
      followed by a rapid improvement of clinical features. Residual skin lesions,
      linear petechia and flares of pale pink erythema used to recur for the next half
      a year. During the follow up, two years later there was no lymph gland
      enlargement, skin rash, or other signs. DISCUSSION: The diagnosis of virus
      associated hemophagocytic syndrome with mild clinical course and seemingly
      spontaneous improvement was established, although it did not fulfill all proposed
      diagnostic criteria. It is possible that it increased the clinical awareness for
      these mild forms in immune-competent patients could account for the improved
      recognition of atypical cases with favorable outcome.

PMID- 19097381
TI  - [Gastrointerstinal stromal tumors of the stomach--case reports].
AB  - INTRODUCTION: Gastrointestinal stromal tumors are the most common mesenchimal
      tumors of the gastrointestinal tract. Despite the enormous progress made in the
      field of diagnostics, most often diagnosis is made during the explorative
      laparotomy and postoperative immunohystochemical analysis of specimen. The
      surgical treatment is often indicated, although scarce preoperative diagnosis
      causes intraoperative dilemma concerning the level of radicality. MATERIAL AND
      METHODS: In this paper we have analyzed two patients with gastric GIST. The first
      patient was 59 years old male, with preoperatively diagnosed colonic cancer.
      Intraoperatively besides the transverse colon cancer, we found intramural gastric
      tumor. This patient underwent subtotal gastrectomy and subtotal colectomy. The
      immunohystochemical analysis of gastric tumor proves benign GIST. The second
      patient was 50 year old male presented with repeated upper GI bleeding. The
      endoscopic ultrasound showed intramural tumor of the anterior gastric wall, with
      a visible blood vessel bleeding during endoscopy. After the resuscitation, we
      performed subtotal gastrectomy. The immunohystochemical analysis proved malignant
      GIST. DISCUSSION: In the cases with inadequate preoperative diagnoses, the level
      of resection procedure is based on the size of tumor and the presence of necrosis
      and bleeding inside the tumor. Tumors larger than 5 cm in diameter with signs of
      necrosis and bleeding are parameters of malignant nature of GIST, therefore
      demanding a radical surgical treatment. CONCLUSION: The surgical resection is a
      treatment of choice for gastrointestinal stromal tumors. It has been shown that
      adequate surgical resection correlates with high 5-years survival rates for
      patients with gastric GIST.

PMID- 19097382
TI  - [Chest computed tomography in the localisation of pathologic processes in
      lymphomas].
AB  - INTRODUCTION: The anatomic localisation of Hodgkin disease and Non-Hodgkin
      lymphoma is very important in the disease prognosis and therapy treatment.
      Intrathoracic localisation in Hodgkin disease is very frequent and usually occurs
      in the form of lymph node enlargement. The most frequent manifestation of the
      thoracic Non-Hodgkin lymphoma is mediastinal and hilarlympha-denomegalia. The
      purpose of this research study is to analyse chest computed tomography findings
      in patients suffering from Hodgkin disease and Non-Hodgkin lymphoma prior to any
      applied therapy. MATERIAL AND METHODS: This retrospective study encompassed 73
      patients diagnosed as having Hodgkin disease or Non-Hodgkin lymphoma. They were
      subjected to III chest CT examinations. The initial occurrence of the disease was
      found in 35 patients (24 patients suffering from Hodgkin disease and 11 suffering
      from Non-Hodgkin lymphoma). Simultaneously, analyses of the pretherapy chest CT
      findings were made. RESULTS AND DISCUSSION: Positive findings were reported in
      66.66% patients suffering from Hodgkin disease and 45.45% patients suffering from
      Non-Hodgkin lymphoma. Enlarged lymphnodes were found in the region of the upper
      mediastinum (parathracheal and prevascular group) in more than 55% of the
      patients suffering from Hodgkin disease and in more than 35% of the patients
      suffering Non-Hodgkin lymphoma. CONCLUSION: The findings of this study coincide
      to a great extent with the findings presented in world literature.

PMID- 19097383
TI  - ["Serbian mother from Scotland"--Dr. Elsie Inglis (1864-1917)].
AB  - INTRODUCTION: 90 years ago, on November 26th, 1917, died Dr. Elsie Inglis, one of
      the greatest heroines of the First World War, founder and driving force of the
      famous "Scottish Women's Hospitals", and one of the most interesting persons in
      the history of medicine in general, and especially in Serbia where she and her
      hospitals were of the greatest help in the most difficult times. CHILDHOOD AND
      EDUCATION: Elsie Maud Inglis was born in India in 1864, in a Scottish family
      which in 1878 moved back to Scotland where Elsie studied medicine and graduated
      from the Edinburgh University in 1899. Medical practice and Women's Movement
      (1894-1914) Dr. E. Inglis worked in Edinburgh, where in 1904. She opened a small
      hospital for women and children called "The Hospice", which was staffed only by
      women. She was also very active in the Women's Movement (the so-called
      suffragettes), fighting for the women's rights and for the Vote. From 1906 until
      1914 she was Honorary Secretary of the Scottish Federation of Women's Suffrage
      Societies. THE FIRST WORLD WAR-THE SCOTTISH WOMEN'S HOSPITALS: After the outbreak
      of the Great War in August, 1914. Dr. E. Inglis immediately organised, through
      her Federation, the so-called "Scottish Women's Hospitals" (SWH), on the whole 13
      of them, which worked through the war in France, Belgium, Serbia, Greece
      (Macedonia), and Russia (Romania). SERBIA, 1915: In.January, 1915 the first Unit
      of the SWH arrived to Kragujevac, and.soon three more hospitals came to Serbian
      towns of Valjevo, Lazarevac and Mladenovac. In May 1915 Dr. E. Inglis herself
      came to Serbia. In October, 1915, when the great offensive of the Central Powers
      began, all these hospitals were evacuated to Krusevac, where they undertook the
      task of nursing 900 Serbian wounded at the "Csar Lazar" military hospital. Dr.
      Inglis and the majority of her staff refused to evacuate any further and stayed
      with their Serb patients. In November, 1915 they became prisoners of war, but
      continued to treat their patients until February, 1916 when they were
      repatriated. RUSSIA, 1916-1917: Back home, Dr. E. Inglis formed a new large SWH
      Unit, which, headed by herself sailed for Russia in August, 1916, and soon joined
      the so-called Yugoslav Volunteer Division, consisting mainly of Serbs, fighting
      on the Dobrudja front. After heavy losses and many retreats the remainder of this
      division, together with the SWH were evacuated back to England, to Newcastle,
      where Dr. E. Inglis, who was already seriously ill, died, on November 26th, 1917.
      She was later buried in Edinburgh, with full military honours. EPILOGUE: High
      honours were bestowed posthumously on Dr. E. Inglis both by Great Britain and
      Serbia, and now, 90 years after her death, we should remember her with deep
      gratitude and respect for all she did for our people in the most difficult times
      of its history.

PMID- 19097384
TI  - Ozone and its usage in general medicine and dentistry. A review article.
AB  - Ozone, an allotropic form of oxygen, is successfully used in the treatment of
      different diseases for more than a hundred years. It is highly valued for various
      effects, such as antimicrobial, antihypoxic, analgesic, immunostimulating etc. on
      biological systems. These mechanisms of action supported with a lot of case
      reports and scientific studies allow using it in different fields of medicine.
      This review of literature is another attempt to summarize different modalities of
      ozone application in dentistry. Further studies are necessary to standardize
      indications and treatment protocols of this promising medical agent.

PMID- 19097385
TI  - Forensic dentistry--identification from the dentist's point of view.
AB  - The paper deals with an identification of missing persons based on a dental
      documentation. The procedure of the identification is presented in two case
      reports with a new possibility of electronic imaging called Dental Cross in
      comparison with classical dental documentation, which is officially used for
      identification of the missing persons by Interpol.

PMID- 19097386
TI  - Bacillus circulans paracardiac infection in non-hodgkin lymphoma--a case report.
AB  - A case report is presented concerning Bacillus circulans paracardiac infection in
      a 27 year old woman with non-hodgkin lymphoma.

PMID- 19097387
TI  - Hippocampal long-term potentiation in adult Lurcher mutant mice: effect of
      embryonic cerebellar graft and motor training.
AB  - Possible effect of trophic factors from embryonic cerebellar graft transplanted
      in adult Lurcher mutant mice on LTP as electrophysiological marker of learning
      and memory process was studied. Also the combination of the transplantation and
      long-term forced motor training was investigated. An evaluation of LTP ability in
      four animal groups (transplanted, sham-operated, with and without forced motor
      activity) and comparison among them showed the highest LTP improvement in the
      group with combination of both influences (ie. transplantation and motor
      training).

PMID- 19097388
TI  - The effect of D1-like receptor blockade on motor functions and spatial learning
      in B6CBA mice.
AB  - Dopaminergic neurotransmitter system plays a role in many neural functions, for
      instance in the motor system. Dopamine also influences cognitive functions,
      motivation and behaviour. In this study, the effect of D1-like receptors blocker
      SCH 23390 on spontaneous motor activity, motor functions and spatial learning in
      adult wild type mice derived from the strain B6CBA was investigated. The animals
      of one group were administered with D1-like receptors blocker SCH 23390 while the
      mice from the other group were treated with the saline solution 20 minutes before
      experiments. Spontaneous motor activity was examined in the open field. Motor
      functions were examined using horizontal wire, ladder and rotarod. Spatial
      learning was tested in the Morris water maze. D1-like receptors inhibition
      significantly decreased spontaneous motor activity. In the horizontal wire test,
      the mice treated with SCH 23390 manifested significantly better results than
      control animals. No significant differences between experimental animals and
      controls were found in the ladder test. On the rotarod, the animals with D1-like
      receptors inhibition reached significantly shorter latencies than the animals
      treated with the saline solution. D1-like receptors blockade led to significant
      impairment of performance in experimental animals in the Morris water maze.
      Spontaneous motor activity and motor skills were influenced by evoked
      hypokinesia. Meanwhile in the horizontal wire test this effect seemed to be
      advantageous, in the rotarod test it meant a definite handicap because this test
      requires good motor coordination and activity. The results gained in the Morris
      water maze indicated that not only hypokinesia played some role there but also
      spatial learning and perhaps motivation were affected. The study confirmed that
      D1-like receptors inhibition has effects on both motor and cognitive functions in
      mice. However the motor effects are not the main cause of the failing in the
      spatial learning test.

PMID- 19097389
TI  - The effect of nitric oxide synthase inhibitors nitro-L-arginine and 7
      nitroindazole on spatial learning and motor functions in Lurcher mutant and wild
      type mice.
AB  - Nitric oxide (NO) is an intercellular messenger that, among other things, plays
      an important role in the nervous system as a gaseous neurotransmitter, modulating
      long-term potentiation (LTP) induction of synaptic transmission. LTP has been
      suggested to be the basis of memory formation. On the other hand NO also
      participates in excitotoxic processes which play an important role in many
      neuropathological states. The aim of this work was to observe the effect of two
      NO synthase (NOS) inhibitors (N omega-Nitro-L-arginine, NA; 7-nitroindazole, NI)
      on spontaneous behaviour, spatial learning and motor functions in Lurcher (+/Lc)
      and wild type (+/+) mice, derived from the B6CBA strain. Heterozygous Lurcher
      mutant mice represent a natural model of the olivocerebellar degeneration. They
      suffer from postnatal, practically total, extinction of cerebellar Purkinje cells
      (due to the excitotoxic apoptosis) and a partial decrease of granule cells and
      inferior olive neurons (ION) because of the lost target of their axons. +/+
      animals are healthy littermates of +/Lc. NA is a nonselective NOS inhibitor which
      influences, except neuronal (n), also endothelial (e) NOS with an impact on blood
      pressure, NI is a selective nNOS inhibitor without any circulatory effect. The
      adult animals of both types (+/Lc; +/+) were influenced by acute administration
      of both inhibitors (25 mg/kg i.p. 30 min. before experiments) and newborns only
      by both acute and long-term administration of NI (1 month, starting from
      postnatal day 2, P2). Control solutions - saline or solvents of both NA and NI
      inhibitors--diluted 1M HCl and dimethyl sulfoxide (DMSO) respectively, were given
      at a relevant volume in the same way. The effect of both inhibitors and control
      solutions on motor functions was tested using four standard procedures
      (horizontal wire, slanting ladder, rotating cylinder, foot-bridge); in newborns
      at the age of 14 days. Spatial learning ability was examined in five-day long
      procedure in the Morris water maze (MWM) (in newborns started on P21).
      Spontaneous behaviour was studied only in adult animals (after acutely
      influencing them) employing the open field method. The results showed, that
      neither the Lurcher mutant, nor wild type mice derived from the B6CBA strain were
      significantly affected by NOS inhibitors NA and NI in spatial learning after both
      the acute and long-term application. Only significant decrease of swimming speed
      was found in both types of mice after the acute administration of NI and in the
      wild type animals after the acute administration of NA. Motor functions were
      significantly negatively affected only in the Lurcher mutants after both the
      acute and chronic application of NI.

PMID- 19097390
TI  - Does cross-fostering modify the impairing effect of methamphetamine on postnatal
      development of rat pups?
AB  - Our previous studies demonstrated that methamphetamine (MA) administered during
      gestation and lactation periods impairs maternal behavior as well as the
      postnatal development of rat pups. The present study tested the hypothesis that
      the cross-fostering influences the development of rat pups. Mothers were daily
      exposed to injection of MA (5 mg/kg) and saline for 9 weeks: three weeks prior to
      impregnation, throughout the entire gestation period and during lactation. As a
      control (C) females with no injections were used. On postnatal day (PD 1), pups
      were cross-fostered so that each mother received some of her own and some of the
      pups of mother with the other treatments. Pup's development and sensorimotor
      coordination was examined between PD 1 and PD 23. Following tests were used: tail
      pull (PD 10), righting reflex on surface (PD 12), righting reflex on mid-air (PD
      17) and rotarod (PD 23). Our results showed that the birth weight in prenatally
      MA-exposed pups was lower than controls or saline-exposed pups regardless of sex.
      Prenatally MA-exposed pups gained less weight than controls or saline-exposed
      pups regardless of postnatal treatment and sex. Further, our data demonstrated
      that prenatal and postnatal MA exposure impairs sensorimotor functions. On the
      other hand, postnatal care of control mothers at least partially suppressed the
      negative effect of prenatal MA exposure. Our hypothesis, that the cross-fostering
      may affect postnatal development of pups, was confirmed. Our results support the
      hypothesis that variation in rat maternal care could serve as a mechanism for a
      non-genomic behavioral mode of transmission of traits.

PMID- 19097391
TI  - Impact of methamphetamine administered prenatally and in adulthood on cognitive
      functions of male rats tested in Morris water maze.
AB  - Studies showed that stimulant drugs that affect the monoaminergic system alter
      both behavioral and cognitive processes. The aim of the present study was to
      investigate the impact of prenatal and acute methamphetamine (MA) exposure on
      cognitive functions of adult male rats tested in Morris water maze (MWM). We
      tested adult male rats prenatally exposed to MA (5 mg/kg), saline or no
      injection. Half of the animals were injected daily with MA (1 mg/kg) after
      finishing the testing. All injections were administered subcutaneously. Three
      types of tests were used: (1) "Place navigation test" (Learning), (2) "Probe
      test" (Probe) and (3) "Retention memory test" (Memory). Our results showed that
      prenatal MA exposure did not affect the test of learning and the Probe test. In
      the test of memory prenatally MA-exposed rats had lower latencies than animals
      prenatally exposed to saline. Further, acute MA administration increased the
      speed of swimming in all rats regardless of prenatal drug exposure and the type
      of test and, however, the increase in the speed was significantly greater in rats
      prenatally exposed to MA than in rats without any prenatal exposure. In addition,
      acute MA application significantly prolonged trajectories in the Place navigation
      test. The present study thus demonstrates that: (1) Prenatal MA exposure does not
      affect learning in the MWM. (2) Prenatal MA exposure increases the sensitivity to
      acute drug injection. (3) Acute MA application impairs learning in the MWM.

PMID- 19097392
TI  - Precision of marginal adaptation of the incisor and molar Procera allceram crown
      copings.
AB  - The primary objective of this in vitro study was to compare the absolute marginal
      discrepancy (AMD) of CAD/CAM produced Procera AllCeram crown copings, fabricated
      on die stone master models of two different tooth groups, incisor and molar. Two
      maxillary central incisors and two first molars typodont teeth were prepared with
      0.8 mm of circumferential chamfer, duplicated 9 times to obtain 36 die stone
      models and allotted into three groups of 12 models (incisors = 6 & molars = 6).
      Procera AllCeram 0.6 mm copings were fixed with zinc phosphate (AZ), glass
      ionomer (AG) and resin (AR) cement accordingly under 50 N static finger force.
      The AMDs were measured using the scanning electron microscope (SEM) on four axial
      walls with 4 measurements on each wall to obtain 16 readings for one tooth.
      Statistical analysis of the data was performed using the non-parametric test of
      Kruskal-Wallis and Mann-Whitney test. The analysis did not find any significant
      differences in the mean AMD of incisor and molar crown copings, and in different
      axial surfaces too (p < or = 0.05). Recorded mean AMD of incisor copings were AZ
      group 59 microm, AG 37.9 microm, and AR 44.4 microm and molar copings were AZ
      48.8 microm, AG 27 microm, and AR 50.2 microm. It can be concluded that AMD of
      Procera AllCeram copings were within accepted level of 100 microm. Incisors
      showed higher AMD than molars. Molars demonstrated the higher AMD on mid-distal
      and mid-lingual surfaces whereas for incisor it was mid-buccal and mid-lingual
      surface.

PMID- 19097393
TI  - Paraneoplastic vasculitis associated with hairy cell leukemia.
AB  - Hairy cell leukemia (HCL) is a rare B-cell lymphoproliferative disease,
      accounting for about 2-3% of all leukemias in adults. The skin lesions were
      described in about 10-12% of patients. Vasculitis in lymphoproliferative disease
      is relatively uncommon and may predate the diagnosis of lymphoproliferative
      disease. A 54-year old female with one month history of general symptoms and
      sudden onset of maculopapular exanthema on the skin, suffered from anemia,
      leukopenia and thrombocytopenia. Examination of the skin biopsy revealed
      lymphocytic vasculitis. Immunophenotyping of the skin biopsy revealed cell
      population with CD45RO, and small groups with CD20, partly DBA44 positivity. Bone
      marrow trepanobiopsy showed 50% infiltration with medium-sized lymphoid cells
      with clear cytoplasm and immunophenotypic coexpression of CD20 and DBA-44
      antigens. The diagnosis of HCL was confirmed by flow cytometry of the bone marrow
      and of the peripheral blood cells that revealed pathological cell population with
      expression of CD11c, CD19, CD25, CD103. The patient was successfully treated with
      a single dose of cladribrine. The patient with acute vasculitis should be
      screened and monitored for possible lymphoproliferative diseases. Skin
      manifestation of acute vasculitis accompanied with hairy cells may be the first
      manifestation of HCL. Purine nucleoside analogue cladribrine is considered as the
      first line of therapy for HCL and induces a total response in more than 80% of
      cases with HCL.

PMID- 19097394
TI  - [Post surgical pain: pathophysiological and therapeutic approaches].
AB  - Post surgical pain is a histonic reality. At the beginning of eighteen century
      (18th), morphine was used for the first time in analgesic aim. Post surgical pain
      is a reality for which takes care of it. The impact of pain pain post surgical in
      Europe is between 31 to 75% as for pain softened instinct, any type of mergened
      surgery. In Africa, the taking care of post surgical pain is not still well
      codified. To take care of it better, is needed a valvation of its intensity,
      analgesic means and a goad strategy.

PMID- 19097395
TI  - [Current aspects of systemic lupus erythematosus in Dakar. About 74 cases].
AB  - INTRODUCTION: previously reported studies on systemic lupus erythematosus in
      Senegal were more then ten years old and reported few cases of patients. Our
      objectives were to update epidemiological, clinical, laboratory and evolutive
      aspects of systemic lupus erythematosus throughout a study of 74 patients.
      PATIENTS AND METHODS: we conducted a retrospective study in the internal medicine
      and the dermatology units of the university teaching hospital Aristide Le Dantec
      from January 1993 to December 2002. All patients with systemic lupus
      erythematosus according to the ACR criteria were included. Those who didn't meet
      ACR criteria were excluded. RESULTS: we included 74 patients; their mean age was
      32 years and the sex ratio 0.1 (male to female). At the entry general symptoms
      were constants, and cutaneous signs were found in 96% of cases, joints signs in
      58.1% and renal sign in 56.8%. Haematological and immunologic abnormalities were
      nearly constant. All the patients received corticosteroids and in 35.71% they had
      in addition immunosuppressive drugs. Shorts term evolution was satisfactory. At
      the medium term 27.02% of the patients were lost and 10.81% of them died.
      CONCLUSION: currents aspects of systemic lupus erythematosus in Dakar are
      improved by the early diagnosis when the disease is pauci-symptomatic and by the
      use immunosuppressive drugs in association with corticosteroids.

PMID- 19097396
TI  - [Frequency of diabetic microangiopathy in newly diagnosed diabetes mellitus in
      Conakry: late diagnosis and lack of screening].
AB  - INTRODUCTION: Diabetes morbidity is not only connected to a scarce therapeutic
      care. It is especially the fact of late diagnosis of diabetes, at a time where
      complications are already present. The aims were to estimate the frequency of
      microangiopathy observed at the time of diabetes diagnosis within diabetic
      patients received in Conakry University Hospital and to describe the clinical
      characteristics of patients who had this complication. PATIENTS AND METHOD: We
      prospectively examined 116 patients [76 men (65.5%) and 40 women (34.5%); 11%
      type 1 diabetes and 89% type 2 diabetes] consecutively received and for whom
      known evolution of diabetes was lower or equal to three-months. All patients were
      interrogated (in search of cardiovascular risk factors), had a systematic check
      for retinopathy (exam done by ophthalmologist) or nephropathy (by measure of
      creatinine, urea and proteinuria). RESULTS: Diabetic retinopathy was present in
      29 cases (24.8%) and diabetic nephropathy in 9 cases (7.8%), one at the stage of
      chronic renal failure. The patients who had microangiopathy were older than the
      others (p = 0.003) and have more frequently Type 2 diabetes (p = 0.005). However,
      glycaemia level and cardiovascular risk factors (nicotine addiction, arterial
      high blood pressure, obesity and sedentary) were not statistically different
      between both groups. CONCLUSION: Diabetic microangiopathy is frequent at the time
      of diabetes diagnosis in Guinea. Thus need for a check-up at the diabetes
      discovery time, as these results point the therapeutic choices and justify
      patient's compliance.

PMID- 19097397
TI  - [Diffuse infiltrative lymphocytosis syndrome (DILS) associated with HIV-1
      infection: first Senegalese case report].
AB  - INTRODUCTION: The "Diffuse Infiltrative Lymphocytosis Syndrome" [DILS] is a
      seldom complication and even very particular case of HIV-1 infection,
      characterized by a merely syndrome and a systemic symptomatology superimposable
      to the figure met during the Gougerot-Sjogren Syndrome. GSS is nevertheless
      underlied by a lymphocyte infiltrate composed mainly of TCD8+ lymphocytes, while
      in the Gougerot-Sjogren syndrome (GSS), the lymphocyte infiltrate is essentially
      composed of TCD4+ lymphocytes. Despite the antiquity and significance of the
      HIV/AIDS pandemic, the DILS is not according to our knowledge individualized in
      the African literature. OBSERVATION: We are reporting a case revealed by a
      polyarthritis associated among others with a merely syndrome and a HIV-1
      infection in a 32 years old Senegalese patient. Her CD4 rate was 327/mm3 and her
      viral load 17052. The biopsy of the accessory salivary glands showed a 4 grade
      lymphocite sialoadenitis according to Chisholm classification. The investigation
      of rheumatoid factors et anti-nuclear antibodies was negative. Under prednisone,
      hydroxychloroquine, methotrexate and tritherapy treatment, the evolution was
      favourable with a current return of 2 years. The rarity of DILS has pushed us to
      study its epidemiological, clinical, paraclinical, physiopathological and
      therapeutical aspects.

PMID- 19097398
TI  - [Pulmonary hypertension revealing systemic diseases: two Senegalese case
      reports].
AB  - INTRODUCTION: Pulmonary hypertension (PH) is a complication of autoimmune
      diseases which worsen the prognosis. In Senegal, a few cases of PH have been
      previously reported in patients with systemic sclerosis. CASE REPORTS: We report
      two cases of patients with PH that revealed autoimmune diseases (Sharp' syndrome
      and Sjogren syndrome). Epidemiological, clinical, evolutive and laboratory data
      were analyzed. Evolution of disease was favourable for one patient and fatal for
      the other. CONCLUSION: These two cases show necessity of early diagnosis of
      systemic diseases in our countries. PH should be screened in each patient with
      autoimmune disease before installation of irreversible pulmonary arterial lesions
      that respond to treatment. New therapy used in idiopathic PH are not yet
      accessible for our patients.

PMID- 19097399
TI  - [Still disease in adult: a Senegalese case report].
AB  - INTRODUCTION: The adult Still's disease is a systematic disease rarely reported
      in the black Africans. We are reporting a case characterized among other
      difficulties by its diagnostic difficulties. OBSERVATION: It is about a 29 years
      old black Senegalese woman patient, without particular antecedents, which
      presented a systematic chronic syndrome composed of a pharyngitis, a
      polyarthritis and general symptoms (fever, chills, sweats, change of the general
      state), a cutaneous eruption, a polyadenopathy, a hepatosplenomegaly. The
      biological analyses showed among others, an inflammatory syndrome (VS at 115 mm
      in the 1st hour, CRP at 100 mg/L, WBC at 10,400/mm3 with neutrophilia), a
      hyperferritinemia in 643 ng/l with collapse of the glycosylated ferritin at 13%
      (N between 60 in 80%). After elimination of any autoimmune or neoplastic
      suppurative infectious pathology in the decline of a check up as exhaustive as
      possible, the diagnosis of a Still disease in adult had been retained. Their was
      improvement under the combination of prednisone and methotrexate. CONCLUSION:
      Although it is exceptional in black African, this pathology shall be however part
      of the differential diagnoses of any unexplained systematic sign. The dosage of
      the ferritinemia and its glycosylated fraction as well as the resort to the
      criteria of Yamaguchi and Fautrel's classification of Still Disease in Adult
      shall allow to establish more prematurely the diagnosis of this potentially
      severe affection.

PMID- 19097400
TI  - [Periodontal status and diabetes: evaluation of 80 patients with diabetes
      mellitus in Conakry Teaching Hospital].
AB  - INTRODUCTION: Dental and periodontal diseases are frequent in diabetics. Few
      studies were carried out on oral pathologies of the diabetics in Africa. The
      objective of this study was to assess periodontal conditions in a population of
      diabetics followed in a hospital environment by comparing them with non
      diabetics. PATIENTS AND METHOD: In a cross-sectional study realized from January
      to April 1999, 80 diabetic patients followed in the Service of Endocrinology were
      compared to 35 non-diabetic patients, chosen among the patients attending in the
      Service of Internal medicine of the Donka Teaching Hospital in Conakry in the
      same period. Both groups were compared according to the simplified oral hygiene
      index (OHIS) and community periodontal index of treatment needs (CPITN). RESULTS:
      There was no difference between diabetics and nondiabetics according to the OHIS.
      Diabetics CPITN index was higher compared to non-diabetics (p = 0.019). In
      diabetics, scores of CPITN increase significantly with duration of diabetes
      mellitus (p = 0.019). Also correlation was found between OHIS and the duration of
      diabetes. Glycemic control was significantly correlated with OHIS (p < 0.001) and
      CIPTN (p < 0.001). CONCLUSION: Diabetic patients have more periodontal treatment
      need than controls. Better collaboration between diabetologist and
      odontostomatologist is needed to preserve the oral health of diabetics.

PMID- 19097401
TI  - [Important pericardial effusions: apport of echocardiography guided
      pericardocentensis: about 30 consecutive cases].
AB  - INTRODUCTION: Western countries have good mastery of abundant pericardial
      effusion while in Africa this still raises some problems regarding diagnosis and
      therapy. The aim was to see to what extent echo guided pericardiocentesis could
      contribute in severe cases. METHODS: All patients with abundant pericardial
      effusion diagnosed by echocardiography with or without compression were
      considered in a prospective study. They experienced a pericardiocentesis. Some
      patients did undergo an additional surgical biopsy. The liquid was preliminarily
      submitted to chemical, bacteriological, cytological analysis. Tissues were
      observed through an anatomic pathology in biopsy. Heart tuberculosis was
      diagnosed through histology for following therapeutic testing. RESULTS: Thirty
      consecutive patients aged 37 in average were included. The sex ratio was 3.75.
      Prior to draining off, 3 neoplasies (2 of lung bronchitis, 1 of cervix ), 1
      leukaemia, 2 extra pericardium tuberculosis and 1 amoebic abscess were diagnosed
      . Clinical occurrence: the most frequent case, besides the tampon (10 cases, i.e.
      30%), was isolated pericardial effusion associated or not with an alteration of
      the global state (13 cases, i.e. 4%). The average quantity of liquid extracted
      was 600c c which provoked a kind of haemorrhage in 18 cases, i.e. 60%.
      Tuberculosis was the major aetiology: 15 cases e i 50% out of which 4 were HIV
      positive. Three additional surgical biopsies were carried out. Seven patients
      died. CCONCLUSION In addition to its diagnostic contribution, echo guided
      pericardiocentesis offers an alternative to endoscopy surgery.

PMID- 19097402
TI  - [Applicability of standard of Demirjian's method for dental maturation in
      Senegalese children].
AB  - INTRODUCTION: the dental age which can be deduced from the stages of dental
      maturation is accepted as being a reliable indicator in the estimate of civil age
      of children whose date of birth is unknown. It is also a good indicator of the
      biological maturity of growing children and the relevance of its use in
      paediatric dentistry and orthodontics was proven. Various methods of
      determination of maturation or dental development from radiographies were
      described. The mostly used method is that of Demirjian. Studies have shown that
      genetic factors could influence the maturation of certain organs. Thus, the
      generalisation of Demirjian standards to others population can be questioned. The
      aim of the present study was to test the applicability of Demirjian's standards
      for the determination of the civil age from dental maturation stages. MATERIAL
      AND METHODS: The dental maturation stages of a randomised sample of 200
      Senegalese children aged from 6 to 14 years (101 boys and 99 girls) was evaluated
      by Demirjian's method. Data collected were converted into Dental Age from the
      conversion charts proposed by Demirjian. The dental age obtained was compared
      with the civil age of the subjects. RESULTS: The results of this study indicate
      that the civil age of the patients was overestimated when evaluated from
      Demirjian's standards (0.89 years for girls and 0.48 years for boys). A linear
      regression equation was then proposed for the correct estimate of the civil age
      from the dental maturation stages.

PMID- 19097403
TI  - [Diagnostic interest of Barr chromatin test in sex determination: about one case
      of male pseudohermaphrodism].
AB  - INTRODUCTION: The Barr chromatin test is a medical cytogenetic test, very quick
      to make, consisting in determination of the percentage of Barr corpuscles that
      correspond to the condensation of the second X chromosome in female epithelial
      cells of mammal, which range between 20 and 50% the percentage of Barr corpuscles
      in male epithelial cells range between 2 and less than 5%). In the less developed
      countries where caryotype isn't realized, this test can give invaluable
      informations about individual sex. The aim of this study was to show the Barr
      chromatin test interest in the sexual ambiguity diagnosis orientation in some
      cases of these sexual ambiguities. PATIENT AND METHODS: To carry this study, we
      have done a Guard coloration on nude nucleus of epithelial cells taken on the
      cheeck internal side of our patient, a 19 years old woman that a gynaecologist
      had sent to us for sexual ambiguity. We have examinated the nude nucleus.
      RESULTS: None of the nude nucleus had showed a Barr corpuscle (0% of Barr
      corpuscles, corresponding to male chromatin sex). CONCLUSION: This rate has gived
      us a Morris syndrome diagnosis orientation; the diagnosis was confirmed later by
      the surgery and by the removal histological study. When caryotype or molecular
      biology are not available, the Barr chromatin test can represent a substitute
      biological test that can contribute to some sexual ambiguity diagnosis.

PMID- 19097404
TI  - [Cytotoxic activity of two cyclic peptides from the latex of Jatropha integerrima
      Euphorbiaceae].
AB  - Activity-guided fractionation of the ethyl acetate extract of the latex of
      Jatropha integerrima Euphorbiaceae combinated with cytotoxic assay against the KB
      human nasopharyngeal carcinoma cells, resulted to the isolation by
      chromatographic methods including HPLC of two new cyclopeptides:
      integerrimacyclopeptide4 and integerrima cyclopeptide B. The amino acid
      composition was established after hydrolysis and derivatization. All chiral amino
      acids were L configuration and were hydrophobic. Their sequences were determined
      by MS fragmentations (ESI-q-TOF, MS/MS) and confirmed by 2D NMR homo- and
      heteronuclear studies. Integerrimacyclopeptide A was a cyclooctapeptide with m/z
      766 corresponding to the molecular formula C37H66N8O9. Analysis of mass spectra
      gave b(n) and a(n) acylium ion series which the sequence could be deduced:
      cyclo(Leu-Gly-Ser-Ile-Ile-Leu-Gly-lle). This structure was confirmed by
      interpretation of HMBC and ROESY spectra. Likewise, integerrimacyclopeptide B was
      a cycloheptapeptide with m/z 651 and C31H53N7O8 as molecular formula containing
      one proline residue: cyclo(Pro-Gly-Thr-Ile-Gly-Ile-Leu). These two cyclic
      peptides exhibited significant cytotoxic activityin vitro against KB tumorales
      cells with respective IC50 values of 0.46 +/- 0.04 and 0.66 +/-0.08 microg/ml.

PMID- 19097405
TI  - [Sarcoidosis in Dakar: 30 case reports].
AB  - INTRODUCTION: Sarcoidosis cases had been rarely reported in Senegal in spite of
      the high frequency of sarcoidosis in black people. The purpose of this work was
      to determine the epidemiological, clinical and evaluative profile of sarcoidosis
      in Dakar. MATERIAL AND METHODS: We performed a multicentric retrospective trial
      in order to characterise sarcoidosis cases in Senegal from 1968 to 2004. RESULTS:
      Twenty cases (21 females and 9 men) were observed. The average age was 40 years.
      Duration before first medical attention was up to one year in 20 cases. Ten
      patients received an anti tuberculosis treatment before sarcoidosis diagnosis.
      Sarcoidosis was a systemic disease in 76% of cases and only cutaneous in 24%.
      Cutaneous lesions were found in 66,66% of cases. Presenting features were
      cutaneous (46%), general (30%), rheumatoid, (16,6%), Lofgren syndrome (3 cases).
      The cutaneous lesions were specific in 94% of cases as small nodules (50%),
      placards (20%), great nodules (15%) and scars sarcoidosis (10%). Extra cutaneous
      involvement were pulmonary (73,33%), lymphadenopathy (66,66%), and rheumatoid
      (20%). Pulmonary tuberculosis was associated in 4 cases. DISCUSSION: Our data
      confirmed rarity of sarcoidosis in Senegal opposite to the high reported
      frequency in other black population in developed country. Clinical features were
      polymorph and the systemic forms predominant. Tuberculosis may be rule out in
      order to avoid miss diagnosis.

PMID- 19097406
TI  - [Central diabetes insipidus: about one Senegalese case].

PMID- 19097407
TI  - [Comparison of three chemiluminescent methods with a radioimmunoassay for
      thyroglobulin measurement in the follow-up of differentiated thyroid cancer].
AB  - INTRODUCTION: Serum thyroglobulin measurements play an integral role in clinical
      evaluation of patients with thyroid cancer. Serum thyroglobulin is a highly
      specific and sensitive tumor marker for detecting persistent or recurrent thyroid
      cancer but also for monitoring clinical status. Actually, chemiluminescent
      methods gain ground on the radioimmunological methods because they offer the
      practical advantage of a shorter incubation time, a wider range of measured
      values and a reagent marked antibody more stable, less fragile than those used on
      radioimmunoassay. The aim of this study was to compare, by correlation study,
      three chemiluminescent methods to the reference radioimmunological method usually
      used in laboratories. MATERIALS AND METHODS: Thyroglobulin was measured in 203
      patients by the 3 following analyzers: Nichols Advantage (Nichols Institute
      Diagnostics, CA, USA), Immulite 2000 ( DPC Roche, Siemens, Los Angeles, USA) and
      Elecsys 2010 (Roche Diagnostics, Manheim, Germany); and by manual method (SELco
      Tg (Medipan Diagnostica, Berlin, Germany). Correlation analysis with OriginLab
      software version 7.0 was performed in order to compare thyroglobulin distribution
      values measured by the different methods. RESULTS: Correlation coefficients
      obtained were for Medipan/ Immulite 2000: 0.95 (n = 80); for Medipan/Elecsys:
      0.97 (n = 31); for Medipan/Advantage: r = 0.96 (n = 73). CONCLUSIONS:
      Chemioluminescent technics we studied could be validly used in patients without
      anti-thyroglobulin antibody. The correlation coefficients we obtained allow us to
      select one of these automated methods after their performance was studied.

PMID- 19097408
TI  - [Traumatic manubriosternal joint dislocation in adult: about two surgical cases].
AB  - Traumatic manubriosternal joint dislocations are rare in adult and occur readily
      during a violent traumatism of the chest and/or the dorsal spine. We report two
      cases treated between September 1997 and August 2002 at the Surgical Emergency
      Department of Le Dantec Hospital. The first observation was related to a 26 year
      old lady. On September 27, 1997, she fell down from a tree and received all the
      weight of the body on her two arms. She was referred because of anterior chest
      pains, increasing with respiration associated with injuries of the 2 wrists. On
      conventional X-ray, a type II manubriosternal joint dislocation (anterior
      dislocation of the sternal body with respect to the manubrium) was diagnosed. The
      mechanism of the dislocation was indirect: flexion-compression of the sternum
      caused by a hyperflexion of the dorsal spine when the patient touched the ground.
      There was also a Pouteaux-Colles fracture of the 2 wrists. The dislocation was
      surgically treated: open reduction followed by manubriosternal stabilization
      using wires. The 2 wrists were treated by Kapandji procedure. At the 21st
      postoperative day, a traumatic rupture of the wires required a 2nd internal
      fixation of the sternum by wires. After 9 years, the patient is without complaint
      and the chest X-ray is normal. The second observation was that of a 19 year old
      young woman, referred on August 15, 2002 after a frontal crash with a car while
      crossing the road. She fell down on her back. She was complaining from severe
      posterior headaches with a normal Glasgow Scale (15), anterior chest and right
      hand pains. Radiological examinations showed a fracture of the occipital bone
      without embarrure and a type I manubriosternal joint dislocation (posterior
      displacement of the sternal body in relation to the manubrium) which mechanism
      was direct: direct shock against the sternum. There were also an isolated
      fracture of 4 right sided ribs and a fracture without displacement of the 3 last
      bones of the right metacarpus. An orthopaedic treatment was carried out for the
      lesions of the right hand and an abstention-monitoring suggested for the
      occipital fracture. The manubriosternal joint dislocation was surgically reduced
      and stabilized by using a braided polyester thread number 2. After 4 years, the
      patient is asymptomatic and the manobriosternal joint is stable. We emphasize on
      the scarcity and the mechanism of traumatic manubriosternal joint dislocations in
      adult, the frequency of associated injuries and the absence of consensus about
      their treatment.

PMID- 19097409
TI  - [Herpes zoster and human imunodeficiency virus in the medical centers of
      Ouagadougou].
AB  - Herpes zoster is an acute posterior ganglio-radiculitis related to the
      reactivation of the chicken pox-herpes zoster virus remained quiescent in the
      neurons of the nerve-knots. It usually occurs at the subject after 60 years old.
      For young patient, it is closely related to the infection by the HIV. Our
      exploratory descriptive and analytical study was carried out from 1 October 2002
      to 30 September 2003, in order to describe the epidemiological, clinical aspects
      of the herpes zoster in the medical formations of the town of Ouagadougou
      (Burkina Faso) and to determine the prevalence of the infection by the HIV in the
      patients. We have collected 118 patients who have a herpes zoster through 6500
      consultants. There were 79 women and 39 men. The average age was 34.4 years. The
      age bracket from 20 to 40 years was the most touched. The blistered eruption was
      the first reason for consultation; the light with type of burn, intermittent pain
      prevailed. The lesions healed in one month but there were 28 ulcerated necrotic
      cases. Post zoster pains have been observed in 33 cases. The localizations were
      the members in 44 cases (37.29%), the head in 35 cases (29.66%) and the trunk in
      40 cases (33.90%). We have observed a case with double localization of herpes
      zoster. On 65 patients tested for the HIV, 58 (89.2%) were infected. The age
      bracket from 20 to 40 was the most concerned. A case of corneal necrosis
      isolated, with blindness and another with an opposed, spasmodic and total hemi
      paresis were notified. Fourteen patients having an antecedent of herpes zoster
      were all infected by HIV. Since the pandemic infection by the HIV, the incidence
      of the herpes zoster increases within the young population. The high frequency of
      HIV infection among our patients (89.2%) showed that the herpes zoster is closely
      related to this disease.

PMID- 19097410
TI  - [Sentinel node biopsy and possibilities of use in current surgical oncology].
AB  - Sentinel node biopsy originally developed for melanoma has gradually extended
      into further fields of surgical oncology. It became a standard procedure in
      melanoma and breast cancer, it appears to be a very helpful method in colorectal
      cancer. The possibilities of use are tested throughout all of surgical oncology
      in gastrointestinal, urological and gynecological tumors. It's importance can be
      displayed even in head and neck tumor, intrathoracical tumors and in thyroid
      cancer.

PMID- 19097411
TI  - [Comparison of dendritic cells antigens in healthy volunteers and monoclonal
      gammopathy of undetermined significance and/or multiple myeloma patients].
AB  - BACKGROUND: Dendritic cells (DCs) are highly specialized antigen-presenting
      cells, which can be used for immunotherapy trials. Functionally normal DCs play a
      critical role in the activation and potentiation of antitumor antigen-specific
      responses. DESIGN AND SUBJECTS: Maturation of DCs from 10 healthy donors, 14
      monoclonal gammopathy of undetermined significance patients and 14 multiple
      myeloma patients was tested in an in vitro study. METHODS AND RESULTS: DCs were
      generated from adherent mononuclear precursors of peripheral blood and cultured
      in presence of IL-4 and GM-CSF with human CD40Ligand stimulation. Serum-free or
      autologous serum conditions were used and expression of significant surface
      antigens, chemokines receptors and production of IL-12p70, were compared. We
      found no difference between groups under serum-free conditions with or without
      CD40L stimulation. Under autologous conditions we found negative effect on
      patients DCs manifested by reduction of some markers. The production of IL-12p70
      was low and no difference in serum IL-6 levels between individual groups was
      found. CONCLUSION: Under serum free conditions there was no difference between
      healthy volunteers, MGUS and patients, but CD40L stimulation did not lead to the
      full maturation ofDCs. Autologous patient serum had negative influence on DCs,
      with no definite dependance on the IL-6 level.

PMID- 19097412
TI  - [Lymphatic mapping in cervical cancer].
AB  - BACKGROUND AND AIMS: The aim of the study is to analyze the feasibility of
      intraoperative sentinel lymph nodes (SLN) detection using gamma detection probe
      and blue dye in patients with cervical cancer. DESIGN AND SUBJECTS: Prospective
      clinical study. 106 patients with cervical cancer were included into the study in
      the period from May 2004 to November 2006. METHODS AND RESULTS: Patients were
      divided into three groups according to the tumor volume. Lymphoscintigraphy was
      performed following an injection of 99m Tc-labeled nanocolloid and
      intraoperatively the SLN were identified visually after marking of lymphatic
      vessels with blue dye and further detected using a handheld gamma detection
      probe. The SLN were histologically and immunohistochemically analyzed. Total
      number of 309 SLN with an average of 2.9 per patient were identified. The SLN
      detection rate was 94.3% per patient, 84.4 % per side, and depended on the tumor
      volume. Metastatic disease was detected in 39 patients (36.8%) and
      micrometastatic disease in 15 patients (14.2%). Sensitivity and negative
      predictive value calculated were 93.9% and 98.0%, false negative rate reached
      5.1. CONCLUSIONS: Intraoperative detection of SLN using combination of technecium
      99-labeled nanocolloid and blue dye represents a feasible, safe and accurate
      technique to identify lymphatic spreading in stages IA2-IB1 of cervical cancer.

PMID- 19097413
TI  - [Radiotherapy induced glioblastoma in a child previously treated for cerebellar
      medulloblastoma (case report and review of the literature)].
AB  - Malignant gliomas represent the most frequent radiotherapy induced ("secondary")
      solid tumor. Their prognosis remains extremely poor despite of aggressive
      multimodal treatment. We present a case report of a 16 years old boy who
      developed cerebellar glioblastoma six years following the combined treatment for
      medulloblastoma. Clinical history, pathological and cytogenetic findings of the
      case are discussed along with treatment possibilities.

PMID- 19097414
TI  - [Breast cancer in young women in the Czech Republic--data from 1989 to 2004].

PMID- 19097415
TI  - [Therapeutic approaches for early stage nonseminomatous germ cell testicular
      tumors].
AB  - The author deales with current therapeutical approaches for early stage
      nonseminomatous germ cell testicular tumours, including preinvasive stage CIS
      (carcinoma in situ). All presented recommendation results from "European
      Association of Urology Guidelines-2007" and are based on respected risk factors
      of the disease progression. When all recommended approaches are kept, then most
      of these patients are fully curable (<95).

PMID- 19097416
TI  - [Treatment of seminoma I stage disease].
AB  - About 35% of men with malignant testicular germ cell cancer are diagnosed with
      seminoma, up to 80% of them with stage I disease. The number of men succesfully
      treated reaches 100%. For many years radiotherapy following radical orchiectomy
      was considered the golden standard for treatment. Treatment efficiency of
      radiotherapy is limited by it's late sequlae, notably gastrointestinal diseases,
      second cancer development, cardiovascular toxicity or infertility. Therefore
      there has been an effort made to minimalise this late toxicity--by radiation
      field reduction, radiation dose reduction, surveilance or chemotherapy with
      carboplatine as a single agent. According to available studies the efficiency of
      radiotherapy reduced either in field area or dose are as efficient as previously
      used radiation regimens and is as efficient as adjuvant chemotherapy with
      carboplatine. On the other hand the results of surveillance studies are
      comparable to those of active therapies, especially in patients with contra
      indications to active treatment especially without prognostic risk factors, i.e.
      tumour size >4 cm, invasion to rete testis, pre-operative elevation of tumoru
      markers (beta HCG). All of the above described treatment modalities (adjuvant
      radiotherapy or chemotherapy and surveillance of patients without risk factors)
      reach comparable 5 years' survival from 93.1% in surveillance to 96% in patients
      after radiotherapy or chemotherapy. Nowadays, according to the new NCCN
      guidelines 2008, we have several options for management strategies for post-
      orchiectomy treatment, i.e., adjuvant radiotherapy, surveillance and newly also
      adjuvant carboplatine - based chemotherapy. In our review article we discuss
      advantages and disadvantages of the various treatment modalities.

PMID- 19097417
TI  - [Chemosensitivity prediction in tumor cells ex vivo--difficulties and limitations
      of the method].
AB  - Certain hope is entertained in the prediction of chemosensitivity in vitro/ ex
      vivo for the purpose of selecting the most effective treatment of malignant
      diseases with minimal patient loading. The possible choice of an effective
      substance based on the results of a simple ex vivo test would increase the
      success of the treatment in case of standard chemotherapy failure or in the
      treatment of primary chemoresistant tumor. MTT test seems to be an easy process
      for the prediction of chemosensitivity of isolated malignant cells ex vivo,
      however each method represents a simple tool, which can provide false results if
      incorrectly preformed. Numerous limitations significantly reduce the successful
      evaluation and constituent aspects of the methodic press to further reflections
      about the proper application of the test.

PMID- 19097418
TI  - [Polymorphism of gene p53 and apoptosis in patients with malignant lung disease-
      our observation].
AB  - BACKGROUND: Many proved alterations in genoms of cells are said to be related to
      tumorigenesis. Apoptosis--a "programmed" death of cell, which has different
      morphology from necrosis, is one of the control mechanisms of cell division and
      participates in tumorigenesis. METHODS AND MATERIAL: The authors present their
      results of analysis of the relation between genetic polymorphism of the p53 gene
      and the level of apopotosis in patients with confirmed malignant lung disease.
      Comparison of genetic polymorphism of the p53 gene in patients with the healthy
      group showed that allocation of BstUI A2 and MspI A1 alleles was significantly
      related to lung cancer. The apoptosis of peripheral lymphocytes was significantly
      increased in lung cancer patients. The highest increase of apoptosis in non-small
      cell lung cancer (NSCLC) group was found in adenocarcinomas. The level of
      apoptosis was also studied in correlation to polymorphism of the p53 gen.
      Substantially higher percentage of apoptotic cells was detected in BstUI 2/2 and
      MspI 2/2 homozygotes. In response to operation a distinctive increase of
      apoptosis in the first and second postoperative day was recorded. Therefore a
      lymphocyte count in peripheral blood was also monitored. The lymphocyte count in
      patients that underwent the operation proved a decrease in absolute and relative
      values. CONCLUSION: Observation of known genetic polymorphisms indicates the risk
      of malignant disease. Together with the analysis of level of apoptosis it may add
      to complexity of the nature of malignant disease or serve as determinants of its
      prognosis.

PMID- 19097419
TI  - [Selective depletion of alloreactive T cells and study of anti-tumor activity of
      specific T cell clones in patients with leukemia].
AB  - BACKGROUND: Graft-versus-host disease (GVHD) is a severe complication of
      allogeneic transplantation of hematopoietic stem cells. Donor T cells play a
      major role in GVHD leading to the host tissue damage, mainly the skin, liver, and
      gastrointestinal tract. A selective depletion using an anti-CD25 immunotoxin can
      eliminate harmful alloreactive T cells while preserving other donor T cells with
      antileukemic and antiinfectious reactivity. PATIENTS AND METHODS: We performed 15
      mixed lymphocyte reactions with clinical specimens from 12 patients with various
      types of leukemia (7x AML, 3x ALL, 1x CML, 1x CLL) and PBMC from 15 healthy
      volunteers from Transfusive station FN Brno Bohunice. RESULTS: In our experiments
      we have demonstrated, that antileukemic (GVL) effect of donor, especially CD4+ T
      cells was well preserved (7.46%), while unfavourable alloreactive (GVH) reaction
      of donor T cells was completely removed. The graft-versus-host (GVH) reactivation
      of donor cells was negligible ever after repeated stimulation with irradiated
      patient's PBMC. CONCLUSION: We have shown that anti-CD25 immunotoxin (IT), RFT5
      SMPT-dgA, launched against alpha chain for human interleukin 2 (IL-2), led to
      long-term selective depletion of alloreactive donor T cell clones while their
      antileukemic activity was well preserved. Base on our results the clinical phase
      I/II study was designed. This study was initiated in year 2007 in three clinical
      centers in Czech Republic.

PMID- 19097420
TI  - [Results of the monitoring the group of patients treated for the Hodgkin disease
      in the period of 1971 to 1996. Part 1: long-time survival in dependence of the
      clinical stage of the disease].
AB  - BACKGROUND: This authors team has been dealing with the Hodgkin disease problems
      since 1971. The MORHO study started at eight working places in 1978 according to
      unified diagnostic and medical protocol. PATIENTS AND METHODS: 370 patients were
      treated. The treatment consisted in the combination of radiation and chemotherapy
      COPP and since 1988 in alternance of COPP and ABVD. Therapy was modificated with
      accordance to clinical stages and patient's histological type and age. Treatment
      of the patients over 50 was reduced in decades of one chemotherapy cycle less.
      RESULTS: Results from the clinical study are--patients with the stage IIA, IIB
      and IIIA survive 30 years in 59.29%, 57.86% and 60.72%. Patients diagnosed as
      stage IIIB survive after 30 years 36.78%, while patients in stages IVA and IVB
      survived 10 years 24.51% and 23.32% and 20 years 8.61% in stage IVB. Women
      survived longer than men. Histological types had no influence to the lenght of
      survival. The total number of relapses in the group was 55. There were 39 men and
      16 women from that. 64% was in stage III and IV and in 73% mediastinal nodules
      were affected. 42% of relapses was till 1 year after the treatment. After the
      treatment 75 children were born to the patients from the group. 60 children from
      that were born to the women under treatment. CONCLUSION: The success of therapy
      of Hodgkin's disease according to protocol created by expert group of study MORHO
      is comparable with results of similar studies in the world. The most important
      contribution of this study was unification of treatment protocol in
      Czechoslovakia. This study changed the formerly paliative therapy to real
      curative treatment.

PMID- 19097422
TI  - [Clinical cancer advances: an annual review--2007].

PMID- 19097421
TI  - [Actual state of ex vivo chemoresistance testing of malignant tumors in Masaryk
      Memorial Cancer Institute Brno].
AB  - Chemoresistance assay results may play a role in cancer management decision
      process. Since August 2006 testing chemoresistance has been tested according to a
      protocol that was designed for this reason in our institute (Masaryk Memorial
      Cancer Institute). Five groups of different types of cancer in particular
      clinical stages were defined for chemosensitivity testing with: (1) metastatic
      malignant melanoma, (2) soft tissue sarcoma (STS), either primary or
      recurrent/metastic, (3) primary or metastatic renal cancer, (4) recurrent ovarian
      cancer and (5) other diagnosis "on clinician's request". In the period from
      September 2006 to November 2007, 25 samples of malignant melanoma (reproducible
      results in 9 cases), 29 samples of STS (relevant data in 11 cases), 36 samples of
      renal cancer (relevant results in 20 samples) and 16 samples of ovarian cancer
      (reproducible results in 11 cases) were acquired. Sensitivity to certain
      chemotherapy agent observed ex vivo does not necessarily mean that the cancer
      would also be sensitive to the same agent in vivo, however, ex vivo resistance
      with following in vivo sensitivity of the tumour has not been observed to date.
      The cultivation of malignant cells is very uncertain in solid tumours, which
      consist of several malignant cell multiclones (benign/stromal cells may outgrow
      malignant cells). This cultivation uncertainty as well as the unique complexity
      of human metabolism makes clinical application of chemoresistance testing at
      least very questionable. The small number of successfully evaluated samples has
      not yet provided us to carry out proper statistical evaluation and clinical
      application.

PMID- 19097423
TI  - [Sanitary and microbiological characteristics of surface waters of Vladivostok
      beaches].
AB  - The present-day sanitary state of most sea beaches within the precincts of
      Vladivostok is mainly determined by the fact that pollutants along with household
      and industrial sewerage flows are carried away into the beaches without proper
      treatment. A multitude of the pathogenic and opportunistic flora with fecal
      sewerage flows enters the coastal zone. In summer holiday months (July and
      August), beach-front areas of the city are polluted with organic substances, i.e.
      they are characterized as polysaprobic, which creates conditions for the
      multiplication of pathogenic microorganisms. In terms of sanitary and
      microbiological indices, the surface waters in the city's recreational zones are
      characterized by persistent fecal pollution that greatly exceeds the sanitary
      standards, abundant enterobacteria, including epidemiologically potentially
      dangerous species.

PMID- 19097424
TI  - [Environmental lead pollution in Ulan-Bator and children's health].
AB  - The paper gives data on environmental lead pollution (ambient air, snow, soil).
      There is a direct correlation between the blood content of lead in children
      living in different microdistricts of Ulan-Bator and the level of environmental
      lead pollution, which results in neurological diseases in children.

PMID- 19097425
TI  - [Hygienic assessment of combined action of ambient air pollutions in the
      localities].
AB  - The paper describes the experimental studies dealing with the reflectory and
      resorptive effects of a gas-vapor-dust-like mixture comprising sulfur dioxide,
      nitrogen dioxide, hydrogen fluoride, and suspension particles. The combined
      effect of the mixture when inhaled by animals was ascertained to present as the
      incomplete summation effect type. In the combined presence in the ambient air,
      the sum of shares of sulfur dioxide, nitrogen dioxide, hydrogen fluoride, and
      suspension particles should not be greater than 0.4 MPC of the isolated effect of
      each agent alone.

PMID- 19097426
TI  - [Prevention of fluorine deficiency in the population of the Altai Territory].

PMID- 19097427
TI  - [Environmental and medical consequences of mineral oil pollution of the
      geological medium].
AB  - The Khanty-Mansi Autonomous District (KMAD) is situated in the central part of
      Western Siberia and referred as to the discomfortably extreme areas equated to
      the Far North. The district occupies a prominent place in Russia's economy in oil
      and gas production and energy generation. More than 30 years' development of
      hydrocarbon deposits in the district has done great damage to the environment and
      nature. Northern ecosystems are slightly resistant to man's impact. The self
      recovery and self-purification of landscapes occur very slowly in the North. The
      studies have established that steady raising of the production of oil and
      petroleum products in the KMAD results in a steady morbidity increase in all
      population groups. It is necessary to take timely preventive measures and better
      informed managerial decisions at the local and regional levels to keep unique
      north nature and the population's health in the North upon increasing man's
      exposure.

PMID- 19097428
TI  - [Environmental contamination with permanent organic pollutants and human health].
AB  - The hottest points of contamination of the environment with permanent organic
      pollutants, including dioxins and polychlorinated biphenyls (PCB) have been
      identified in Russia. These are located in different regions of the country where
      DDT, PCB, and other chlorine-containing compounds have been earlier manufactured.
      Despite discontinuance of their production, the environment and foodstuffs show
      the high levels of these substances. The world's highest content of dioxins in
      breast milk and blood is noted in the dwellers of Chapayevsk and Ufa. In these
      towns, there are changes in the population's health, which are typical of the
      action of permanent organic pollutants.

PMID- 19097429
TI  - [Influence of chemical soil pollution on the population's health].
AB  - The author integrates information on the hygienic value of man-made chemical soil
      pollution on the population's health. He presents the results of studies of the
      pollution of soil and its contacting media (the sources of drinking water supply,
      ambient air, and crop production) with priority chemicals (heavy metals,
      pesticides, nitrates, nitrocompounds). The newborns and children under 14 years
      of age may run the greatest danger of being exposed to toxicants since all the
      protective systems of their organism are imperfect and are being formed.

PMID- 19097430
TI  - [Effect of chemicalization agents on gynecological cancer in the republic of
      Daghestan].

PMID- 19097431
TI  - [Evaluation of the impact of an increased flight duty period on flight safety].
AB  - Scientific rationale has been provided for the qualitative indices of the time of
      flight from the studies of the impact of a gradual (by small values) increase in
      the time of flight on its safety and the health of airmen. Analysis of the 2003
      2004 flight safety trends, by studying the specific changes in a flight crew's
      working load from the pilot performance quality index and airmen's health status
      revealed no negative impact of an annual working load increase on the incidence
      of diseases leading to pilots' medical disqualification. Flight safety indices
      did not become worse when the flight timeout was increased up to 90 hours during
      30 successive hours and 900 hours during a year. Increasing the load of 90 and
      particularly 100 hours during 30 successive days may present a potential threat
      to flight safety.

PMID- 19097432
TI  - [Search for optimal combinations of the hygienic and protective characteristics
      of body armors].
AB  - The protective composition of a body armor is generally characterized by two
      major parameters--the area and level of protection, i.e. resistance to bullets
      and fragments. These characteristics directly depend on the mass of a body armor
      and the sizes of the body's screening. The positive protective characteristics
      simultaneously have a negative impact on the most important hygienic indices of a
      body armor, such as convenience and easiness-to-use. The optimum combination of
      protective and performance characteristics of body armors makes a compromise
      between their mass and the level of protection.

PMID- 19097433
TI  - [Assessment of an association of nutrition and a special contingent's health].
AB  - This paper considers the association of nutrition habits with the development of
      various noninfectious diseases, including chronic diseases. Stress that is
      followed by arrest and juridical processes, in combination with other factors
      attended by criminal sanctions as imprisonment also negatively affect the health
      status of a special contingent of the penitentiary system. Our studies have
      ascertained the association between the qualitative and quantitative composition
      of food and the health status of convicts.

PMID- 19097434
TI  - [Dietary iodine provision of the population in the Krasnoyarsk Territory].
AB  - The paper analyzes the time course of changes in the intake of staple foods in
      the Krasnoyarsk Territory in 1998-2005. It is shown that the ingestion of iodine
      rich foods has not increased greatly and it is low and does not provide the
      population with this essential micronutrient. The actual content of iodine in the
      study samples of food and its raw material is several times less than the
      tabulated values. The contribution of the staple foods to the provision of the
      Krasnoyarsk Territory's population with iodine is assessed. The total level of
      dietary iodine deficiency is estimated. Iodine-fortified salt and foods should be
      widely used under special conditions providing the transportation and storage of
      biologically value foods, during which there are inevitable losses of the trace
      element occur.

PMID- 19097435
TI  - [Assessment of age-related changes in adaptive capacities in Angarsk children].

PMID- 19097436
TI  - [Assessment and correction of psychophysiological features in adolescents at the
      information science lesions].
AB  - The adaptation of teenagers to an educational process in a computer class with
      the optimum hygienic parameters was studied. The modified procedure "Examinees'
      emotional assessment of musical tracks" was established to efficiently prevent
      autonomic dysfunctions and emotional disorders.

PMID- 19097438
TI  - [Cardiovascular performance in Yamal adolescents in adapting to academic
      activity].
AB  - The combined use of cardiointervalography and an orthostatic test allows detailed
      assessment of the adaptive capacities of the cardiovascular system. The paper
      gives the results of examination of 60 healthy adolescents from Yamal. Adjustment
      mechanisms have been assessed by means of hemodynamic parameters in boys and
      girls.

PMID- 19097437
TI  - [Hygienic assessment of lifestyle and health status in 10th-11th-form pupils
      directed to have a higher medical education].
AB  - Ninety-seven pupils from the 10th-to-11th classes formed on a competitive basis
      for intensive education, for forming motivation for future medical profession
      were examined using a set of psychophysiological tests that could evaluate the
      central nervous and cardiovascular systems, psychophysiological adaptation, task
      performance, and personality traits. The vast majority of the examinees were
      found to follow the hygienic recommendation of the day regimen, which
      corresponded to the principles of healthy lifestyle. In 99% of the pupils, mental
      capacity was rated as fair (66%) and high (33%), as evidenced by
      psychophysiological testing. Fifty-six per cent of the examinees were observed to
      have mental adaptive disorders that might reflect age-related psychological
      immaturity in them at the completing stage of schooling.

PMID- 19097439
TI  - [Age- and gender-specific features of Kemerovo schoolchildren's health].
AB  - The paper presents the results of studying the health status of Kemerovo
      schoolchildren from the parameters of their physical health and adaptation
      potential. Characteristic changes in these parameters have been ascertained in
      different age- and gender-specific groups. Overall, there are progressive
      decreases in their physical health and functional capacities with age.

PMID- 19097440
TI  - [Free radical processes and erythron in pregnant rats and their fetuses in
      chronic nitrite intoxication].
AB  - The purpose of the investigation was to study changes in the intensity of induced
      chemiluminescence of serum and erythrocytes, as well as the erythrocytic system
      in pregnant rats and fetuses in chronic nitrite intoxication. In nitrite
      intoxicated pregnant rats, the level of erythropenia was less than that in intact
      pregnant rats, fetuses being observed to have stimulated erythropoiesis. In
      intact pregnant animals, the intensity of induced chemiluminescence on day 20 was
      higher than the baseline and throughout the follow-up in nitrite-intoxicated
      adult animals and fetuses.

PMID- 19097442
TI  - [Impact of purified drinking water use on the small bowel lymphatic region].
AB  - The structures of the mesenteric lymph nodes, small bowel, microvascular bed, and
      a mast cell population of the mesentery of rats were studied by light microscopy.
      Tap water, filtered water, and macro- and microelement-balanced water were used.
      The use of the filtered and macro- and micro-element water caused increases in
      lymph transport in the mesenteric lymph nodes and in the height of small
      intestinal villi, activated humoral immunity, and produced the most optimum level
      of a mast cell population and the structure of the mesenteric microvascular bed.

PMID- 19097441
TI  - [Protective role of cobalt complexes of porphyrin and phthalocyanine in acute
      nitrite intoxication and endotoxic shock in an experiment].
AB  - There is currently an active search for effective agents to regulate the content
      of nitric oxide (NO) in the body. One of the ways of reducing its blood
      concentration may be the binding of NO by different complexions that comprise the
      metal complexes of porphyrins and phthalocyanines. The study was undertaken to
      evaluate the protective effect of synthetic metal complexes of porphyrin and
      phthalocyanine in acute nitrite intoxication and endotoxic shock. The findings
      suggest that both study samples of the synthetic metal complexes have not
      prevented hemolytic anemia in acute nitrite intoxication and endotoxic shock;
      however, they have shown potential sorption properties against nitrate ions in
      the blood and brain of experimental animals, which may be the subject of a
      further study.

PMID- 19097443
TI  - [Adaptation of bioluminescence technique for the evaluation of the toxicity of
      mineral waters].
AB  - Mineral waters have been ascertained to exert a pronounced inhibiting effect,
      that is in proportion in their mineralization and pH values, on the fluorescence
      of microbial luminescent biosensors. To prevent such adverse reactions masking
      the effects of chemical pollutants, the authors propose an adjusted procedure for
      preparing the samples of mineral waters for luminescence biotesting. The first
      approach is to differentially insert additional quantities of NaCl into the test
      samples depending on the level of their baseline mineralization to the baseline
      value 3 g/l, which is provided in the use of the natural sea luminescent
      bacterium Photobacterium phosporeum as a test object (Microbiosensor B-17 677f).
      The second approach is to normalize pH to values of not more than 7.5, which are
      identical in the use of both the Microbiosensor B-17 677f and a recombinant
      Escherichia coli strain with the cloned lux-operon P. leiognathi (Ecolum-9). This
      sample preparation maintaining the baseline fluorescence of bacterial biosensors
      is shown to permit bioluminescence detection of exogenously inserted toxicants in
      the test samples.

PMID- 19097444
TI  - [Sociohygienic monitoring of domestic drinking water supply in the Krasnoyarsk
      Territory].
AB  - Based on the results of sociohygienic monitoring, the authors give an integrated
      hygienic assessment of chemical and microbial contamination of water sources,
      drinking water, the sanitary state of water pipes, and risks for diseases in the
      Krasnoyarsk Territory. The changes occurring in 2001-2005 in the parameters of
      domestic and drinking water supply have been ascertained to be transient
      processes. Associations and quantitative dependences have been established
      between the content of barium, the microbial contamination of drinking water and
      the rates of a number of communicable and non-communicable diseases. Hygienic
      criteria and indicators for substantiating varying preventing measure programs
      are proposed.

PMID- 19097445
TI  - [To the appropriateness of using the admissible maximum permissible concentration
      excess principle in water hygiene].

PMID- 19097446
TI  - [Life and scientific work of P. V. Dunayev during Chkalov-Orenburg period].

PMID- 19097447
TI  - S.O.S (seeking out staff).

PMID- 19097448
TI  - My pet peeves.

PMID- 19097449
TI  - Pitt opens expansive center for special needs patients.

PMID- 19097450
TI  - Flouridation effort gains momentum across the state.

PMID- 19097451
TI  - Leadership and the Pennsylvania Dental Association.

PMID- 19097452
TI  - The Tenth District--an overview of the Dental Society of Western Pennsylvania.

PMID- 19097453
TI  - What is the connection between practice and research?

PMID- 19097454
TI  - Changing behavior: evidence based practice supporting hair removal with clippers.
AB  - Evidence based practice demonstrates using clippers immediately before surgery,
      when perioperative hair removal is necessary, results in the fewest surgical site
      infections (Kjonniksen, Andersen, Sondenaa, & Segadal, 2002). In addition, one of
      The Joint Commission's national patient safety goals for 2008 is "to reduce the
      risk of healthcare associated infections" (The Joint Commission, 2008, Goal 7).
      Therefore, a project was undertaken to change perioperative nursing care in a
      large teaching hospital from using razors for hair removal in the perioperative
      setting to using clippers. Change is difficult and encompasses many
      interdisciplinary areas. A description of the process of utilizing evidence to
      change behavior in the perioperative setting and its outcomes will be provided in
      this paper. Klevens, et al., (2007) reported that 22% of healthcare associated
      infections were the result of surgical site infections (SSIs). Changing practice
      to utilizing clippers for hair removal is an extrinsic factor of SSIs that can be
      easily modified. Otorhinolaryngology (ORL) patients that require hair removal
      before surgery (i.e., acoustic neuroma, cranial-facial resections, and head and
      neck reconstruction) may benefit from this change in practice. Perioperative
      nurses are in a prime position to reduce the incidence of SSIs in ORL patients.

PMID- 19097455
TI  - The basics of evidence-based practice: suggestions for nurse managers.

PMID- 19097456
TI  - Snoring remedies--are they all appropriate?

PMID- 19097457
TI  - The presidential candidates on healthcare.

PMID- 19097458
TI  - Physician preferences for medical interventions in elderly patients.
AB  - PURPOSE: To identify factors influencing medical decision making in the elderly
      based on differences in age, cognition, and function. MEASUREMENTS: Physicians
      were given a clinical scenario and asked to select from three management options
      based on the patients' characteristics. RESULTS: Eighty-six percent would offer
      aggressive management to patients less than 85 years of age, whereas only 47.2%
      would offer similar care to those over 85 years of age (RR 0.5; 95% CI: 0.4-0.7).
      Physicians were less likely to offer aggressive management for patients with
      dementia (RR 0.2; 95% CI: 0.1-0.6), and for those requiring home assistance (RR:
      0.2; 95% CI: 0.1-0.6) compared to those without dementia or functional
      limitations. CONCLUSION: Physicians are more likely to deny aggressive management
      to functionally active adults over 85 years of age, and to those with dementia or
      functional impairment irrespective of age.

PMID- 19097459
TI  - Transplantation of a unilateral fused kidney with inferior ectopia:
      revascularization utilizing donor aorta and vena cava.
AB  - We present a case of kidney transplantation utilizing a fused kidney with
      inferior ectopia. The kidney had three arteries, five veins and two ureters and
      was procured en bloc with the donor vena cava and aorta. The caudal end of the
      donor vena cava was anastomosed to the recipient's external iliac vein. The right
      common iliac artery of the donor, in continuity with the donor aorta, was
      anastomosed to the recipient's external iliac artery. The two ureters were
      implanted separately. The patientwas discharged home with a serum creatinine of
      0.9 mg/dl. Through innovative techniques, kidneys that may not have been
      transplantable in the past can now be used with excellent results. This is the
      first known report of transplantation using a unilateral fused kidney with
      inferior ectopia.

PMID- 19097460
TI  - Sequencing an educational activity.
AB  - Sequencing is applying an explicit logic to the order of activities within a CME
      program to maximize learning outcomes. Given existing educational needs and any
      performance gap, sequencing requires educators to consider the steps necessary to
      bring participants along a continuum of learning. The concept of sequencing can
      be applied to the program itself as well as to other CME activities that may
      complement the program.

PMID- 19097461
TI  - Universal health care--60 years of the British National Health Service 1948-2008.
AB  - The British National Health Service (NHS) is now 60 years old, affording an
      opportunity to examine its performance as a government-funded health plan
      covering all citizens. It opened in 1948 and by 1949 patients' demands on
      services far exceededestimates. Since then spendinghas increased yearly. There
      have been manyrecurringproblems particularly limitation of services due to
      underfunding and long waiting lists for treatments reaching a high of 1,263,000
      patients awaiting hospital admission in 1998. In an attempt to solve its problems
      the NHS has been reorganized frequently. Major redesigns have occurredwith each
      newgovernment, accompaniedby increased costs
      andagrowingbureaucracy.Administrative and clerical staff grew from 29,021 in 1951
      to 280,692 (+867%) in 2005. Significant problems continue. The NHS is an example
      of what can go wrong with a wholly government funded universal health care plan
      that is free at the point of delivery.

PMID- 19097462
TI  - Medical delegation: get the facts.

PMID- 19097463
TI  - Early events in the development of inhalation therapy. 1958.

PMID- 19097464
TI  - Meditations on primary care.

PMID- 19097465
TI  - Whither the history and physical?

PMID- 19097466
TI  - What is primary care case management?

PMID- 19097467
TI  - Address of the Executive Director. CSMS House of Delegates--annual meeting.
      September 24, 2008.

PMID- 19097468
TI  - Address of the Keynote Speaker. CSMS House of Delegates--annual meeting.
      September 24, 2008.

PMID- 19097469
TI  - Address of the new President. CSMS House of Delegates--annual meeting. September
      24, 2008.

PMID- 19097470
TI  - Patient safety.

PMID- 19097471
TI  - Functional implication of gait after left or right-sided stroke.
AB  - OBJECTIVE: To quantify and compare parameters of muscle electrical activity and
      ground reaction force of lower limb during gait in post-stroke patients with left
      or right side functional involvement. METHOD: Fifteen post-stroke volunteers with
      left side functional involvement were age, gender and weight matched and compared
      to fifteen post-stroke volunteers with right side functional involvement.
      Comparison was executed by means of electromyography with four pairs of surface
      electrodes positioned on the affected side (spastic side), on the muscles rectus
      femoris, tibialis anterior, soleus, and medial portion of the hamstrings, and
      with a ground reaction force plate. RESULTS: There was no statistically
      significant difference on electromyographic activity of analyzed muscles (p =
      0.6), nor on the analysis of ground reaction vertical forces, stride duration,
      weight bearing index, gait velocity, cadence and stride length (p = 0.53).
      CONCLUSION: According to the electromyographic parameters and to the ground
      reaction force during gait among the post-stroke volunteers with right or left
      side involvement; we could suggest that functional rehabilitation presented no
      differences for these individuals.

PMID- 19097472
TI  - Electromyographic and neuromuscular analysis in patients with post-polio
      syndrome.
AB  - Proceed to a comparative analysis of the electromyographic (EMG) activity of the
      muscles rectus femoris, vastus medialis and vastus lateralis, and to assess
      muscle strength and fatigue after maximal isometric contraction during knee
      extension. Eighteen patients with post-polio syndrome, age and weight matched,
      were utilized in this study. The signal acquisition system utilized consisted of
      three pairs of surface electrodes positioned on the motor point of the analyzed
      muscles. It was possible to observe with the results of this study a decreased
      endurance on initial muscle contraction and during contraction after 15 minutes
      of the initial maximal voluntary contraction, along with a muscle fatigue that
      was assessed through linear regression executed with Pearson's test. There were
      significant differences among the comparative analysis of EMG activity of the
      muscles rectus femoris, vastus medialis and vastus lateralis after maximal
      isometric contraction during knee extension. Initial muscle contraction and
      contraction after a 15 minute-rest from initial contraction decreased
      considerably, indicating a decreased endurance on muscle contraction, concluding
      that a lower limb muscle fatigue was present on the analyzed PPS patients.

PMID- 19097473
TI  - Evidence of muscle role over the cranio-facial skull development in Angle's Class
      III dental malocclusion under the clinical rest position.
AB  - OBJECTIVE: The purpose of this study was to investigate correlations between
      masseter muscle activity and cephalometric measures in Angle's class III dental
      malocclusion under the clinical rest position. METHODS: Eight volunteers, both
      sex, age 7-12, were submitted to an electromyographic analysis of the masseter
      muscle, subdivided in the upper, medium and lower regions, and to a cephalometric
      analysis of 15 angle and linear measurements. After normalization, the data was
      subjected to a statistical, non-parametric Spearman correlation test, by means of
      the SPSS 12.0 program. RESULTS: Statistically significant correlations were
      observed between the clinical rest condition before and after the execution of
      exercises (a serie of mandibular movements), and the cephalometric measurements
      angle SN GoGn, angle SNA, angle SNB, angle SND, upper incisive. NA angle, upper
      incisive-NA distance, lower incisive. NB angle, lower incisive-NB distance and
      angle IMPA, and the different regions of the masseter muscle. CONCLUSIONS: The
      significant statistical correlation found between the cephalometric analysis and
      the function of the masseter muscle indicate a strong influence of the
      musculature under a clinical rest condition over the cranial-facial development
      in the Angle's class III dental malocclusion. There is a selective activity of
      the different regions of the masseter muscle under the clinical rest condition in
      the Angle's class III dental malocclusion. There is a demand for research to
      complement these findings in other classes of dental malocclusion.

PMID- 19097474
TI  - Finger movement improves ankle control for gait initiation in patients with
      Parkinson's disease.
AB  - The purpose of this study was to investigate the effect of finger movement on
      ankle control for gait initiation in patients with Parkinson's disease (PD
      patients). The subjects were 13 PD patients and 6 age-matched healthy adults. The
      subjects moved fingers before or after gait initiation, or initiated gait without
      finger movement. Ankle joint movement in the stance leg was recorded to estimate
      the duration of ankle dorsiflexion (DIF duration), which reflects the degree of
      disturbance in ankle control for gait initiation in PD patients. In the PD
      patients with prolonged D/F duration, finger movement that preceded gait
      initiation shortened the D/F duration, but in the PD patients without prolonged
      D/F duration and in healthy subjects, the effect was not found. Accordingly,
      finger movement that precedes gait initiation improves ankle control for gait
      initiation in PD patients who suffer disturbance in ankle control for gait
      initiation.

PMID- 19097475
TI  - Neuropathy patterns differ in patients with diabetic complications.
AB  - PURPOSE: Diabetic polyneuropathy (PNP) is an important risk factor for foot
      ulcers. Diabetic dermopathy is more frequent in patients with diabetic
      neuropathy. We compared clinical and electrophysiological characteristics of PNP
      localizations/recurrences of foot ulcers, and diabetic dermopathy (DD) between
      sexes. METHODS: Eighty-eight diabetic patients (44 men, 44 women) had an
      evaluation regarding detailed history of their diseases, lesion-related data, and
      clinical examination. Nerve conduction velocities (NCV), compound motor action
      potentials (CMAP), distal latencies (DL), and sensory nerve action potentials
      were assessed from the right and left peroneal, right median/ulnar nerves.
      RESULTS: The presence of DD was more common in men (p < 0.001). The mean NCV of
      ulnar nerves was slower (p < 0.001); mean CMAP values were lower (p = 0.006); and
      mean DL was longer in men with compared to women (p = 0.003). Although EMG
      features of peroneal nerves showed no significant difference, diabetic men had
      more common and severe peroneal nerve involvement (p = 0.004). Carpal tunnel
      syndrome was more common in women, though not significant. Patients with right
      sided ulcers had lower CMAP amplitudes on the right peroneal nerves in regard to
      left peroneal nerves (p = 0.009). CONCLUSIONS: Our findings suggest that ulnar
      nerves are more commonly involved in men, with lower CMAP slower NCV values, and
      longer DL values.

PMID- 19097476
TI  - Influence of trunk muscle co-contraction on spinal curvature during sitting
      reclining against the backrest of a chair.
AB  - Today, many office workers frequently adopt a relaxed or slumped sitting posture
      for many hours, and often people tend to spend their leisure time reclining
      against the backrest of a chair while sitting for a long time, as when watching
      television. While sitting, the pelvis rotates backwardly, and lumbar lordosis is
      flattened. Simultaneously, the load on the intervertebral discs and spine
      increases. Sitting in a slumped position is known to increase disc pressure even
      more, and to aggravate chronic low back pain (CLBP). Therefore, it is very
      important to teach workers and often people about the correct sitting posture. In
      addition, it has been recognized that co-contraction of the deep spine
      stabilizing muscles enhances lumbar segmental stability and the sacro-iliac
      joint. However, little is known about the influence of co-contraction of the
      trunk deep muscles on spinal curvature during sitting reclining against the
      backrest of a chair. The purpose of this study was to compare the EMG
      (electromyographic) activity of the trunk muscles during slump sitting with that
      during co-contraction and to investigate how this cocontraction influences spinal
      curvature. Ten healthy male volunteers (20.8 +/- 0.8 years old) without CLBP
      participated in the study. Bipolar surface electrodes were attached to the rectus
      abdominis, the obliquus externus abdominis, the obliquus internus abdominis, the
      lower back extensor muscles (L3) and the multifidus on the right side. The EMG
      signals were continuously recorded during slump sitting and co-contraction of the
      trunk muscles, reclining against the backrest of chair. They were amplified, band
      pass filtered, digitized and stored by a data acquisition system. The average
      muscle activity values over the five-second sample for each sitting posture were
      normalized to maximal voluntary contractions (%MVC). While the subjects performed
      both sitting postures, the curvature of the spine was measured using a new skin
      surface and hand-held device, the "Spinal Mouse". More significant activities of
      the trunk muscles, with the exception of the rectus abdominis and the lower back
      extensor muscles (L3), were observed during co-contraction of the trunk muscles
      than during slump sitting. The co-contraction of the trunk muscles resulted in
      significantly less lumbar curvature and more sacral angle than during slump
      sitting. The thoracic curvature showed no significant change during either
      sitting posture. The results of this study indicated that co-contraction of the
      trunk muscles during sitting reclining against the backrest of a chair could
      bring about the correct lumbar curvature, effectively stabilize the lumbopelvic
      region, and decrease focal stress on passive structures.

PMID- 19097477
TI  - Comparative analysis of electromyographic pattern in the forearm muscles of
      hemiplegic patients.
AB  - It was purposed the use of electromyography (EMG) to evaluate the activation of
      the agonists and antagonists muscles of spastic patients, to test the viability
      in the development of an instrument that given quantitative data of the patient
      spasticity. 30 hemiplegic and 15 normal volunteers had been submitted to the EMG
      of flexor and extensor carpi ulnaris muscles during the flexion and extension
      movements of the wrist. The individuals with less severe spasticity (mAS
      (modified Ashworth Scale) ringing 0 to 3 degree), had presented deficit in the
      activation of the flexor muscles in plegic side in relation to the non plegic
      side and that the individuals seriously compromised by the spasticity (mAS = 4
      degree) present deficit of reciprocal inhibition. One evidenced is that the non
      plegic member does not present a similar neuro-motor comportment when compared to
      the normal member. The surface electromyography is a practical clinical
      instrument to evaluate the patient with spasticity and the hemiplegic patient
      needs to be evaluated on both sides (deficient and no deficient) because the no
      compromised side do not show a normality standard.

PMID- 19097478
TI  - Multiple arm lipomatosis and posterior interosseus nerve palsy.
AB  - BACKGROUND: Lipomas are common benign soft tissue tumours which tend to be
      indolent and risk free. Lipomas rarely spread in the deep soft tissue causing
      posterior interosseous nerve (PIN) neuropathy. METHODS (CASE DESCRIPTION): We
      present two patients with multiple lipomatosis of the arms and PIN paralysis,
      with a brief review of the cases reported in literature. RESULTS AND CONCLUSION:
      We emphasize the role of electromyographic study as unique methodical capable to
      reveal an early radial nerve damage, permitting an optimal post-surgical nerve
      function recovering.

PMID- 19097479
TI  - Behavior of emg activation of rectus femoris, vastus lateralis and vastus
      medialis muscles during maximum contraction before and after a series of repeated
      efforts.
AB  - The proposal of this study was to analyze the behavior of electromyographic
      activity of the Rectus Femoris, Vastus Lateralis and Vastus Medialis muscles
      during Maximum Isometric Voluntary Contraction (MIVC) performed before (MIVC-1)
      and after (MIVC-2) the series of repeated effort (four series of 12 repetitions)
      of the movement of extending the knee performed on an extending table with 80% of
      maximum load (1RM) during 15 seconds each MIVC. The participants were 10 soccer
      players (average age of 17.7 +/- 0.67, average corporal mass of 67.07 +/- 6.06 kg
      and average height of 174.6 +/- 4.98 cm). Surface electrodes (disposable) were
      used. The frequency established was 1024 Hz (Low/High pass at 600/10 Hz). The
      statistical treatment employed analysis of variance (ANOVA) for repeated
      measurements followed by the HSD post hoc test of Tukey. The level of
      significance adopted for all analyses was p < 0.05. For the Rectus Femoris muscle
      the value expressed in RMS referring to MIVC-1 was 346.97 +/- 63.93 and MIVC-2
      was 287.58 +/- 61.03 (p = 0.06) corresponding to 82.88% of MIVC-1. Regarding the
      Vastus Lateralis muscle the value in MIVC-1 was 385.50 +/- 120.23 and in MIVC-2
      it was 316.87 +/- 67.85 (p = 0.04) corresponding to 82.19% of MIVC-1. For the
      Vastus Medialis muscle MIVC-1 value was 430.88 +/- 84.23 and MIVC-2 was 396.32 +/
      70.40 (p = 0.03) corresponding to 91.97% of MIVC-1. Results demonstrated that
      the muscles presented action potencies during the actions performed, being
      greater in MIVC-1. The Rectus Femoris muscle presented electromyographic signals
      of lesser amplitude than the Vastus Lateralis and Vastus Medialis muscles. The
      Vastus Medialis muscle presented a greater percentage value between MIVC-1 and
      MIVC-2. The Rectus Femoris muscle was the first to present signs of fatigue.

PMID- 19097480
TI  - Lessons learned from coordinating research on the North Atlantic (CORONA).

PMID- 19097481
TI  - Comparative ecology of North Atlantic shores: do differences in players matter
      for process?
AB  - The contrasting histories of the western and eastern shores of the North Atlantic
      Ocean provide an excellent opportunity to consider the implications of past
      events for present ecological processes and the functioning of marine ecosystems.
      Similarities and differences in assemblage composition have been driven by large
      scale events, such as the trans-Arctic interchange, which has shaped the species
      pool, and cycles of glaciation, which have determined phases of local or regional
      extinction and colonization. More recently, anthropogenically induced invasions
      and local extinctions have significantly altered biogeographic distributions.
      Here we consider for both hard and soft substrata how the presence or absence of
      key taxa influences the outcomes of trophic and other biological interactions,
      and evaluate the consequences for community structure and ecosystem functioning.
      On intertidal hard substratum shores, biodiversity of epilithic microphagous
      grazers differs across latitudinal and longitudinal scales. Diversity is high in
      southern Europe but declines to the north and across the Atlantic. Lower
      diversity and the absence of patellid limpets in Iceland and the northwest
      Atlantic compared to Europe result in differences in consumer pressure, and an
      apparent contrast in the importance of herbivory vs. competitive interactions and
      predation pressure as community structuring processes. Interestingly, despite
      differences in "process," community patterns are remarkably similar between the
      east and west. On soft sediment shores, there are conspicuous geographic
      differences in importance of bioturbators and large digging predators.
      Hemichordates can be abundant and important infaunal bioturbators in the western
      Atlantic, but they generally play a much reduced role in the eastern Atlantic. In
      addition, the number and diversity of digging predators on western Atlantic
      shores is high; the horseshoe crab, swimming portunid crabs, large whelks,
      excavating waterfowl, and an abundance of skates and rays exert intense predation
      pressure and associated biogenic disturbance to sediments. In Europe, except for
      excavating waterfowl these taxa are rare or absent. Thus, the importance of
      large, biological agents of disturbance is lower on European shores as a
      consequence of both recent anthropogenic pressure and natural processes over
      larger time scales. Consideration of key structuring taxa over the Atlantic shows
      that human-mediated transport has had considerable influence. Faunas on both
      sides of the Atlantic are becoming more similar to the point that some of the key
      differences in assemblage composition and hence community organization have
      blurred. Recent introductions as well as planned experimental manipulations
      provide the opportunity to understand the role of species identity in determining
      community structure and ecosystem functioning over large spatial scales; the
      North Atlantic may be an ideal test system to explore these areas.

PMID- 19097482
TI  - Arctic climatechange and its impacts on the ecology of the North Atlantic.
AB  - Arctic climate change from the Paleocene epoch to the present is reconstructed
      with the objective of assessing its recent and future impacts on the ecology of
      the North Atlantic. A recurring theme in Earth's paleoclimate record is the
      importance of the Arctic atmosphere, ocean, and cryosphere in regulating global
      climate on a variety of spatial and temporal scales. A second recurring theme in
      this record is the importance of freshwater export from the Arctic in regulating
      global- to basin-scale ocean circulation patterns and climate. Since the 1970s,
      historically unprecedented changes have been observed in the Arctic as climate
      warming has increased precipitation, river discharge, and glacial as well as sea
      ice melting. In addition, modal shifts in the atmosphere have altered Arctic
      Ocean circulation patterns and the export of freshwater into the North Atlantic.
      The combination of these processes has resulted in variable patterns of
      freshwater export from the Arctic Ocean and the emergence of salinity anomalies
      that have periodically freshened waters in the North Atlantic. Since the early
      1990s, changes in Arctic Ocean circulation patterns and freshwater export have
      been associated with two types of ecological responses in the North Atlantic. The
      first of these responses has been an ongoing series of biogeographic range
      expansions by boreal plankton, including renewal of the trans-Arctic exchanges of
      Pacific species with the Atlantic. The second response was a dramatic regime
      shift in the shelf ecosystems of the Northwest Atlantic that occurred during the
      early 1990s. This regime shift resulted from freshening and stratification of the
      shelf waters, which in turn could be linked to changes in the abundances and
      seasonal cycles of phytoplankton, zooplankton, and higher trophic-level consumer
      populations. It is predicted that the recently observed ecological responses to
      Arctic climate change in the North Atlantic will continue into the near future if
      current trends in sea ice, freshwater export, and surface ocean salinity
      continue. It is more difficult to predict ecological responses to abrupt climate
      change in the more distant future as tipping points in the Earth's climate system
      are exceeded.

PMID- 19097483
TI  - The trans-Atlantic history of diversity and body size in ecological guilds.
AB  - Geographically separate biotas often show differences in species composition,
      diversity, and adaptations. Such differences, which often reflect historical
      differences in regimes of productivity and selection, have received little
      attention from ecologists. Here we concentrate on diversity and maximum body size
      in 18 guilds of shallow-water marine shell-bearing mollusks and barnacles from
      the European and North American sides of the temperate North Atlantic. These
      guilds represent suspension-feeders (epifaunal, shallow infaunal, and deep
      infaunal), chemosymbiotic bivalves, predators, and grazers. Geographic patterns
      among Recent guilds were compared to those during Pliocene and early Miocene time
      in order to determine how diversity and maximum size changed over the last 17
      million years in the face of high levels of extinction and species invasion.
      Recent European guilds are generally more diverse than their American
      counterparts, a finding consistent with previous biota-wide analyses. Diversity
      within Pliocene guilds was often higher on the American side, but this stems in
      part from the large subtropical component in preserved temperate Pliocene guilds
      in Virginia but not in Europe. The largest species in hard-bottom guilds in
      Europe reach greater sizes than those in comparable American guilds, but for sand
      bottom guilds, American species almost always attain greater sizes than their
      European counterparts. These size differences have changed little since early
      Miocene time despite high levels of Pliocene and Pleistocene extinction in
      invasion, particularly on the American side. Large-bodied species are
      overrepresented among both extinct and invading lineages, meaning that lineage
      replacement has been the rule for the largest species in guilds on both sides of
      the Atlantic. Together with previous studies, these results may imply that sand
      bottom environments in North America have been more productive and have
      experienced more far-reaching escalation between shell-bearing species and their
      predators than their European counterparts since early Miocene time. The Pliocene
      to Recent record of hard-bottom guilds implies that productivity and/or
      escalation in these systems may have been higher on the European side than in
      eastern North America. Shallow-water guilds on opposite sides of the Atlantic
      have retained differences despite great upheavals caused by extinctions and
      invasions during the last 3 million years.

PMID- 19097484
TI  - Climatic influences on deep-sea ostracode (Crustacea) diversity for the last
      three million years.
AB  - Ostracodes are small, bivalved crustaceans with the finest-scale fossil
      resolution of any metazoan, rivaled only by the fossil record of the protistan
      Foraminifera. This article presents a synthesis of the patterns and possible
      causes of alpha species diversity variation in benthic deep-sea ostracodes at
      drilling sites in the North Atlantic and Arctic Oceans. Taken together, these
      sites represent a period of great climatic variability covering the past three
      million years. Sediment cores taken from the Mid-Atlantic Ridge show a positive
      correlation between warm temperatures and high species diversity. These Mid
      Atlantic Ridge cores, at the same latitude as northern Spain, show the same
      positive correlation during the last two glacial-interglacial cycles (200-0 ka
      [thousands of years ago]) as they do during the pre-glacial Pliocene 2.85-2.4 Ma
      (millions of years ago). This positive correlation is also found in Pliocene
      cores from the Rockall Plateau, at the same latitude as Ireland. During the last
      200 thousand years, however, this correlation is reversed in cores taken from
      both the Rockall and Iceland Plateaus. The discovery of high diversity during
      colder periods in recent high-latitude Rockall and Iceland cores seems to be
      explained by spikes in diversity caused by ice-rafting events, which would not
      affect the lower-latitude Mid-Atlantic Ridge. The Heinrich ice-rafting events
      reduce North Atlantic surface temperatures and salinity every approximately 6-12
      ka, dramatically decreasing surface productivity. This increase in diversity
      during Heinrich events may be explained either by a negative correlation between
      surface productivity and benthic diversity or by increase in diversity caused by
      moderate disturbance when ice rafted debris fall to the bottom of the ocean.

PMID- 19097485
TI  - The relation between productivity and species diversity in temperate-Arctic
      marine ecosystems.
AB  - Energy variables, such as evapotranspiration, temperature, and productivity
      explain significant variation in the diversity of many groups of terrestrial
      plants and animals at local to global scales. Although the ocean represents the
      largest continuous habitat on earth with a vast spectrum of primary productivity
      and species richness, little is known about how productivity influences species
      diversity in marine systems. To search for general relationships between
      productivity and species richness in the ocean, we analyzed data from three
      different benthic marine ecosystems (epifaunal communities on subtidal rock
      walls, on navigation buoys in the Gulf of St. Lawrence, and Canadian Arctic
      macrobenthos) across local to continental spatial scales (<20 to >1000 km) using
      a standardized proxy for productivity, satellite-derived chlorophyll a.
      Theoretically, the form of the function between productivity and species richness
      is either monotonically increasing or decreasing, or curvilinear (hump- or U
      shaped). We found three negative linear and three hump-shaped relationships
      between chlorophyll a and species richness out of 10 independent comparisons.
      Scale dependence was suggested by more prevalent diversity-productivity
      relationships at smaller (local, landscape) than larger (regional, continental)
      spatial scales. Differences in the form of the functions were more closely allied
      with community type than with scale, as negative linear functions were restricted
      to sessile epifauna while hump-shaped functions occurred in Arctic macrobenthos
      (mixed epifauna, infauna). In two of the data sets, (St. Lawrence epifauna and
      Arctic macrobenthos) significant effects of chlorophyll a co-varied with the
      effects of salinity, suggesting that environmental stress as well as productivity
      influences diversity in these marine systems. The co-varying effect of salinity
      may commonly arise in broad-scale studies of productivity and diversity in marine
      ecosystems when attempting to sample the largest range of productivity, often
      encompassing a coastal-oceanic gradient.

PMID- 19097486
TI  - Climate and recruitment of rocky shore intertidal invertebrates in the eastern
      North Atlantic.
AB  - Studies of the impacts of climate and climate change on biological systems often
      attempt to correlate ecological responses with basin-scale indices such as the
      North Atlantic Oscillation (NAO). However, such correlations, while useful for
      detecting long-term trends, are unable to provide a mechanism linking the
      physical environment and ecological processes. Here we evaluate the effects of
      the NAO on recruitment variability of rocky intertidal invertebrates in the North
      Atlantic examining two possible climate-related pathways. Using a highly
      conservative test we interpret associations with the NAO integrated over a season
      (three months) as an indicator of atmospheric effects on newly settled recruits
      (NAO3), and the effects of the NAO integrated over six months (NAO6) as an
      indicator of changes in ocean circulation affecting patterns of larval transport.
      Through an extensive literature survey we found 13 time series, restricted to
      southwest Ireland and Britain and comprising five species, that could be used for
      statistical analysis. Significant correlations with NAO3, our proxy for
      atmospheric effects, were observed in the south-central domain of our study
      region (southwest Ireland and south England). Significant correlations with NAO6,
      the proxy for ocean circulation effects, were detected on southwest Ireland. The
      associations were detected for three (two barnacles and a topshell) at two sites.
      These results suggest that the NAO can have effects on the recruitment of
      intertidal invertebrates through different pathways linked to climate and be
      distributed heterogeneously in space. Based on previous evidence and the sign and
      geographic location of significant correlations, we suggest that winter NAO
      effects are likely to occur as a result of effects on the survival of early life
      stages settling during spring or through changes in phenology. Our results argue
      that a combination of modeling and synthesis can be used to generate hypotheses
      regarding the effects of climate on recruitment and aid in the design of field
      based tests of explicit ecological mechanisms.

PMID- 19097487
TI  - Ecological genetics in the North Atlantic: environmental gradients and adaptation
      at specific loci.
AB  - The North Atlantic intertidal community provides a rich set of organismal and
      environmental material for the study of ecological genetics. Clearly defined
      environmental gradients exist at multiple spatial scales: there are broad
      latitudinal trends in temperature, meso-scale changes in salinity along
      estuaries, and smaller scale gradients in desiccation and temperature spanning
      the intertidal range. The geology and geography of the American and European
      coasts provide natural replication of these gradients, allowing for population
      genetic analyses of parallel adaptation to environmental stress and
      heterogeneity. Statistical methods have been developed that provide genomic
      neutrality tests of population differentiation and aid in the process of
      candidate gene identification. In this paper, we review studies of marine
      organisms that illustrate associations between an environmental gradient and
      specific genetic markers. Such highly differentiated markers become candidate
      genes for adaptation to the environmental factors in question, but the functional
      significance of genetic variants must be comprehensively evaluated. We present a
      set of predictions about locus-specific selection across latitudinal, estuarine,
      and intertidal gradients that are likely to exist in the North Atlantic. We
      further present new data and analyses that support and contradict these simple
      selection models. Some taxa show pronounced clinal variation at certain loci
      against a background of mild clinal variation at many loci. These cases
      illustrate the procedures necessary for distinguishing selection driven by
      internal genomic vs. external environmental factors. We suggest that the North
      Atlantic intertidal community provides a model system for identifying genes that
      matter in ecology due to the clarity of the environmental stresses and an
      extensive experimental literature on ecological function. While these organisms
      are typically poor genetic and genomic models, advances in comparative genomics
      have provided access to molecular tools that can now be applied to taxa with well
      defined ecologies. As many of the organisms we discuss have tight physiological
      limits driven by climatic factors, this synthesis of molecular population
      genetics with marine ecology could provide a sensitive means of assessing
      evolutionary responses to climate change.

PMID- 19097488
TI  - Evaluating signatures of glacial refugia for North Atlantic benthic marine taxa.
AB  - A goal of phylogeography is to relate patterns of genetic differentiation to
      potential historical geographic isolating events. Quaternary glaciations,
      particularly the one culminating in the Last Glacial Maximum approximately 21 ka
      (thousands of years ago), greatly affected the distributions and population sizes
      of temperate marine species as their ranges retreated southward to escape ice
      sheets. Traditional genetic models of glacial refugia and routes of
      recolonization include these predictions: low genetic diversity in formerly
      glaciated areas, with a small number of alleles/haplotypes dominating
      disproportionately large areas, and high diversity including "private" alleles in
      glacial refugia. In the Northern Hemisphere, low diversity in the north and high
      diversity in the south are expected. This simple model does not account for the
      possibility of populations surviving in relatively small northern periglacial
      refugia. If these periglacial populations experienced extreme bottlenecks, they
      could have the low genetic diversity expected in recolonized areas with no
      refugia, but should have more endemic diversity (private alleles) than recently
      recolonized areas. This review examines evidence of putative glacial refugia for
      eight benthic marine taxa in the temperate North Atlantic. All data sets were
      reanalyzed to allow direct comparisons between geographic patterns of genetic
      diversity and distribution of particular clades and haplotypes including private
      alleles. We contend that for marine organisms the genetic signatures of northern
      periglacial and southern refugia can be distinguished from one another. There is
      evidence for several periglacial refugia in northern latitudes, giving credence
      to recent climatic reconstructions with less extensive glaciation.

PMID- 19097489
TI  - Serum zinc and copper status in dyslipidaemic patients with and without
      established coronary artery disease.
AB  - INTRODUCTION: Aspects of trace element status have previously been investigated
      as possible contributory factors to atherosclerosis. In this present study a more
      comprehensive approach has been taken, looking at the relationship between
      dietary macro- and micronutrient intake, serum concentrations of zinc and copper,
      and markers of inflammation in dyslipidaemic patients with or without established
      coronary artery disease (CAD) and healthy controls, so that a clearer
      understanding of the potential relationship between copper and zinc status and
      coronary disease may be ascertained. METHODS AND MATERIALS: Dyslipidaemic
      patients (n = 238) were recruited from the local General Hospital in Guildford,
      UK. Fifty-five of these patients had established CAD. Control subjects (n = 135)
      were recruited from among employees at the local University and Hospital. A
      validated food frequency questionnaire was used for estimating the dietary intake
      of zinc and copper. RESULTS: Serum copper, copper/caeruloplasmin ratio,
      zinc/copper ratio, and C-reactive protein (CRP) were significantly different in
      the patient groups compared to controls [serum copper: 17.20 +/- 0.2 v 15.91 +/-
      0.29 micromol/L, p < 0.001; copper/caeruloplasmin ratio: 111.37 +/- 2.18 v 100.63
      +/- 2.93 micromol/g, p < 0.01; zinc/copper ratio: 0.85 +/- 0.01 v 0.90 +/- 0.01,
      p < 0.05; and CRP: 1.25 (0.42-3.26) v 0.58 (0.17-1.42) mg/L, p < 0.001]. Dietary
      protein, total fat, starch, fibre, monounsaturated fat, zinc, and zinc/copper
      ratio were also significantly higher in the patients compared to controls.
      Patients with established CAD had significantly higher serum CRP (p < 0.05) and
      lower serum zinc (p < 0.01) and zinc/copper ratio (p < 0.01) compared to both
      patients without CAD and healthy controls. CONCLUSION: Significant differences in
      copper and zinc status, dietary intake and markers of inflammation were observed
      in patients with dyslipidaemia, with or without established CAD, compared with
      control subjects. Differences in serum CRP, copper and caeruloplasmin may be
      related to a heightened state of inflammation. The imbalance in zinc/copper
      metabolism may either contribute to the CAD risk or be a consequence of an acute
      phase response.

PMID- 19097490
TI  - Advanced glycated human serum albumin as AGE-carrier protein in enzyme-linked
      immunosorbent assay.
AB  - Competitive ELISAs for advanced glycation end product (AGE) measurements are
      based on anti-AGE-antibody and in vitro prepared AGE-carrier competitive antigen.
      AGE-human serum albumin (HSA) prepared by non-enzymatic reaction between protein
      and glucose is often used as a competitive antigen. The aim of the study was to
      examine the impact of pH on AGE-HSA preparation. The sets of AGE-HSA analyzed by
      gel filtration chromatography, IEF and UV/VIS showed significant modifications of
      native albumin. A competitive ELISA was developed by using polyclonal-AGE
      antibody and in vitro prepared AGE-HSA at pH 4.5-8.0. AGE-HSA preparations showed
      an impact on the ELISA ability to recognize AGE-immunoreactivity of serum
      proteins. The highest AGE-immunoreactivity was recorded with the antigen prepared
      at pH 4.5; detection limit declined by approximately 50% with antigens prepared
      at pH 6.5, 7.5 or 8.0. Study results confirmed the impact of pH on the glycation
      adduct formation, thus significantly modifying the results of competitive ELISA
      measurements.

PMID- 19097491
TI  - Comparison of high-sensitivity C-reactive protein serum assay results obtained
      using Dade-Behring BNII nephelometer and Ortho Vitros FS 5.1 clinical analyzer in
      respect of CRP-related risk assessment of chronic metabolic diseases.
AB  - BACKGROUND: Serum concentration of high sensitive C-reactive protein (hsCRP) can
      predict the risk of chronic metabolic and cardiovascular diseases but it is
      unclear whether turbidimetric high sensitive assays of CRP are adequate. METHODS:
      Concentrations of serum CRP in 126 samples of serum were measured with high
      sensitivity methods using nephelometry (BN II Nephelometer) and turbidimetry
      (Ortho Vitros FS 5.1). RESULTS: For CRP concentrations measured by nephelometry
      and turbidimetry intra-assay CVs were 3.2 and 0.9% at mean CRP concentrations of
      1.4 and 2.1 mg/l, inter-assay CVs for commercial controls were 3.1% and 3.6% at
      mean concentrations of 1.3 and 1.7 mg/l, and mean biases were 7.62% and 2.26%,
      respectively. Measurements were strongly, linearly correlated (r = 0.99; CRP
      vitros = 0.03 +1.03 CRP (BN II)). When disease risk was assessed by nephelometry
      and turbidimetry, results were similar. If the risk of disease was classified as
      moderate (1.0 < CRP < or = 3.0 mg/l) or high (CRP > 3.0 mg/l), the frequency of
      misclassified cases was only 2.3 and 2.1%, respectively. The classification
      agreement weighted kappa coefficient was 0.94 (95% C.I.: 0.89-0.98). CONCLUSIONS:
      turbidimetric high sensitive CRP assays can properly classify CRP-related
      prediction of chronic metabolic diseases with special consideration on
      cardiovascular risk.

PMID- 19097492
TI  - Clinical performance of six different serum tartrate-resistant acid phosphatase
      assays for monitoring alendronate treatment.
AB  - Two forms of tartrate-resistant acid phosphatase (TRACP) circulate in human
      blood, TRACP 5a derived from inflammatory macrophages and TRACP 5b derived from
      osteoclasts. We compared the clinical performance of the following TRACP
      immunoassays for monitoring alendronate treatment in postmenopausal women: 1)
      TRACP 5b activity using a selective pH; 2) TRACP 5b activity using a selective
      substrate; 3) Total TRACP activity; 4) Total TRACP protein amount; 5) TRACP 5a
      activity; 6) TRACP 5a protein amount. TRACP and other bone turnover markers were
      measured before the start of treatment and at 3 months. Alendronate treatment
      decreased TRACP values determined with assays 1, 2 and 3, and had no effect on
      the values determined with assays 4, 5 and 6. Clinical performance of assays 1, 2
      and 3 was good, and these assays correlated with each other and with the other
      bone markers. This study showed that TRACP 5b specific methods are useful for
      monitoring changes in bone resorption during alendronate treatment, and
      alendronate treatment does not affect serum TRACP 5a levels.

PMID- 19097493
TI  - Eliminating heterophilic antibody interference for ferritin detection using
      Olympus F(ab')2 based reagent.
AB  - Interferences with the Olympus immunoturbidimetric assay for ferritin have been
      reported because the antibodies used in the immunoassay are derived from rabbits.
      Rabbits are familiar pets known to be a risk factor for developing heterophilic
      (or interfering) antibodies. This report shows how the current Olympus Ferritin
      assay has been improved to eliminate the interference from heterophilic
      antibodies.

PMID- 19097494
TI  - Comparison of performance of classical clinical chemistry analysers with test
      strip devices (Reflotron) and those based on film technology (Vitros) in external
      quality assessment (EQA) surveys.
AB  - This article reports on the performance of two "dry" chemistry devices,
      (Reflotron, Roche Diagnostics and Vitros, Johnson & Johnson) and compared them
      with classical "wet" chemistry analysers in four commercially produced quality
      assessment samples (Roche PNU and PPU and Seronorm Human and Human High Controls)
      sent repeatedly over a 12-month observation period. Eleven analytes (including
      five enzymes) were studied, eight of which had target values set by reference
      method procedures. The results showed that both devices gave comparative results
      for the same sample sent in different EQA-surveys. Statistically significant
      differences which occurred were due to the high precision of measurement with a
      minimal shift in the measured concentrations. They had no clinical relevance in
      interpretation of results. Comparisons between "dry" and "wet" chemistry results
      for the same analyte were almost always statistically significantly different and
      often large enough to influence the clinical interpretation of results. Examples
      here were glucose and uric acid measured with the Reflotron and compared with
      other Roche devices (Cobas, Hitachi). The Vitros showed deviant values for urea
      and creatinine, when compared with other measuring devices using liquid reagents.
      Differences seen were constant over time, but must be seen in context with the
      matrices of the samples sent. The results show the long term stability of both
      reagents and test kits, a necessary prerequisite for long-term controlling of
      precision and indirectly accuracy of patient measurements.

PMID- 19097495
TI  - Likelihood ratios reporting in a tertiary hospital emergency department; a pilot
      study.
AB  - The Emergency Department and the laboratory of our institution jointly developed
      simple Clinical Pathways for some important clinical conditions (pulmonary
      embolism, acute myocardial infarction, bile-pancreatic disease) and since May
      2004 the positive and negative likelihood ratios have been added to the reports
      of the tests included in the clinical pathways. In the first semester 30% of
      clinicians adopted the new mode of tests requesting AMI, Pulmonary embolism and
      bile pancreatic clinical pathways, respectively, 24% 32% and 42%. According to a
      survey carried out in 2004 all the ED staff had knowledge of the project. A real
      partnership developed between the laboratory staff and Emergency Department
      physicians leading to the adoption of the Evidence Based Laboratory Medicine
      tools in the decision making process.

PMID- 19097496
TI  - Prospective comparative evaluation of an office-based rapid immunological test
      with a Guaiac-based fecal occult blood test for colorectal cancer screening in
      general population with average-risk.

PMID- 19097497
TI  - Comparison of a novel fecal marker--fecal tumor pyruvate kinase type M2 (M2-PK)
      with fecal calprotectin in patients with inflammatory bowel disease: a
      prospective study.

PMID- 19097498
TI  - [Relationship between electroacupuncture-induced regulatory effect on leukocytes
      and the caliber of splenic sinusoid basal lamina eyehole on rabbits].
AB  - OBJECTIVE: To study the underlining mechanism of electroacupuncture (EA) in
      regulating leukocyte counts in the rabbit. METHODS: A total of 75 rabbits were
      randomly divided into normal control, leukocytosis model, leukocytosis + EA,
      leukopenia model, leukopenia+EA groups, with 15 cases in each. EA (2-20 Hz, 1-2
      mA) was applied to "Dazhui" (DU 14), bilateral "Zusanli" (ST 36) and bilateral
      "Geshu" (BL 17) for 20 min, once daily for 5 days. Leukocytosis and leukopenia
      models were duplicated by intravenous injection of coliform (0.1 ml/kg) and
      cyclophosphamide (30 mg/kg) separately. Peripheral blood leukocyte counts were
      detected every day. At the end of the experiment, the rabbit's spleen tissue was
      collected under anesthesia, and the diameter of splenic sinusoid basal lamina
      eyehole was measured under scanning electronic microscope. RESULTS: Compared with
      normal control group, after i.v. coliform and cyclophosphamide, leukocytes
      increased and decreased significantly and respectively, while the area of the
      splenic sinusoid basal lamina eyehole in leukocytosis model group increased
      lightly and that of leukopenia model group reduced obviously (P < 0.01). In
      comparison with their individual model group, the leukocyte count in leukocytosis
      + EA group decreased considerably (P < 0.05), while that of leukopenia + EA group
      increased markedly (P < 0.01). The area of splenic sinusoid basal lamina eyehole
      in leukocytosis+ EA group decreased apparently (P < 0.05), and that in
      leukopenia+ EA group increased remarkably (P < 0.05). CONCLUSION EA is able to
      regulate the leukocyte counts in coliform-induced leukocytosis and
      cyclophosphamide-induced leukopenia rabbits, which may be related with its
      effects in improving the splenic sinusoid basal lamina eyehole activity.

PMID- 19097499
TI  - [Selection of basic acupoints for composing "gastric-disorder-formula" for
      electroacupuncture prevention of acute gastric mucosal lesion in rats].
AB  - OBJECTIVE: To select the best combination of the commonly-used acupoints
      [Zhongwan (CV 12), Neiguan (PC 6), and Zusanli (ST 36)] for treatment of gastric
      disorders. METHODS: Forty-eight Wistar rats were randomly divided into 8 groups:
      model, ST36, CV12, PC6, ST36 + PC6, ST36 + CV12, CV12 + PC6 and ST36 + CV12 + PC6
      by factorial design method. Acute gastric mucosal lesion model was established by
      intragastric perfusion of anhydrous alcohol. EA(1- 3 mA, 30 Hz) was applied to
      the above-mentioned acupoints for 20 min respectively. And after EA, gastric
      mucosal lesion index (LI), pathological lesion integral score (PLIS) were
      calculated and mucosal ultramicrostructural changes observed by optical
      microscope and transmission electron microscope respectively. RESULTS: Compared
      with model group, the gastric mucosal LI and PLIS of ST36, CV12, PC6, ST36 +
      CV12, ST36 + PC6, CV12 + PC6, ST36 + CV12 + PC6 groups all decreased
      significantly (P < 0.05). Comparison among 7 EA groups showed that both LI and
      PLIS of ST36 + CV12 + PC6 group were significantly lower than those of ST36, V12,
      PC6, ST36 + CV12, ST36 + PC6 and CV12 + PC6 groups (P < 0.05). No significant
      differences were found between every two groups of ST36, CV12, PC6, ST36+ CV12,
      ST36 + PC6 and CV12 + PC6 groups (P > 0.05) in both LI and PLIS. Ultrastructural
      results showed that the injury of gastric mucosal parietal cells and delomorphous
      cells including mitochondrial swelling, crista arrange disorder and breaking,
      enlargement of the rough endoplasmic reticulum, ribosome exfoliation, etc. in
      model group was serious, but lightened significantly in EA groups particularly in
      ST36 + CV12 + PC6 group. CONCLUSION: ST36, PC6 and CV12 combination can
      effectively reduce anhydrous alcohol-induced gastric mucosal lesion in rats, and
      may be used as a basic formula

PMID- 19097500
TI  - [Effect of electroacupuncture on NMDAR-2 B mRNA expression in hippocampal tissue
      in vascular dementia rats].
AB  - OBJECTIVE: To study the underlying mechanism of electroacupuncture (EA) in
      improving learning-memory ability in vascular dementia (VD) rats. METHODS: SD
      rats were randomized into control, sham operation (sham), VD model, non-acupoint
      and acupoint groups, with 10 cases in each. VD model was established by occlusion
      of the bilateral common carotid arteries. Morris water maze test was performed to
      detect the rats' learning-memory ability. The expression of N-methyl-D-aspartate
      receptor (NMDAR)-2 B mRNA in hippocampal CA 1 region and dentate gyrus was
      measured by hybridization in situ. EA (2 Hz, 1-2 mA)was applied to "Baihui" (GV
      20), "Dazhui" (GV 14) and bilateral "Shenshu"(BL 23) and non-acupoint (the chest
      abdominal juncture between the first and the second lumbar vertebrae) for 20 min,
      once daily for 30 days. RESULTS: Self-comparison showed that 6 weeks after
      modeling, the escape latencies of control and sham groups, and the lingering
      duration in the 3rd quadrant of water pool of model, non-acupoint and acupoint
      groups decreased significantly (P < 0.05), while the escape latencies of model,
      non-acupoint and acupoint groups, and the lingering duration of control and sham
      groups increased considerably (P < 0.5). No significant differences were found
      between control and sham groups, and among model, non-acupoint and acupoint
      groups in the escape latency and the lingering duration in the 3rd quadrant (P >
      0.05). On the 11th week after modeling, compared to their individual escape
      latencies and lingering duration on the 6th week, the escape latencies of
      controll sham and acupoint groups shortened obviously (P < 0.05), while the
      lingering duration in the 3"rd quadrant of the same 3 groups postponed
      significantly (P < 0.05). Compared with model group, the escape latency of
      acupoint group shortened obviously and the lingering duration increased
      significantly (P < 0.05). No significant differences were found between control
      and sham groups, and between model and non-acupoint groups in these two indexes
      (P > 0.05). Compared to control/sham group, the grey values of NMDAR-2 BmRNA
      expression in hippocampal CA 1 region and dentate gyrus in model and non-acupoint
      groups decreased significantly (P < 0.05). Compared to model group, the grey
      values of NMDAR-2 B mRNA expression in these two brain regions increased markedly
      (P < 0.05). No significant difference was found between control and sham groups,
      and between model and non-acupoint groups (P > 0.05). CONCLUSION: Acupoint-EA is
      able to improve VD rats' learning-memory ability which may be related to its
      effect in upregulating the expression of NMDAR-2 B mRNA in hippocampal and
      dentate gyrus.

PMID- 19097501
TI  - [Effect of acupotomy lysis on serum matrix metalloproteinase (MMP)-3 and MMP-13
      contents in osteoarthritis rabbits].
AB  - OBJECTIVE: To observe the effect of acupotomy lysis on serum matrix
      metalloproteinase (MMP)-3 and MMP-13 contents in osteoarthritis (OA) rabbits.
      METHODS: A total of 34 New Zealand rabbits were randomly divided into normal
      group (n = 7), model group (n = 7), acupotomy group (n = 10) and
      electroacupuncture (EA) group (n = 10). OA model was established by left-hindlimb
      joint-immobilization method. Acupotomy lysis was applied to the affected joint,
      once a week for 3 weeks. EA (2/100 Hz, 2 mA) was applied to "Yinlingquan" (SP 9),
      "Yanglingquan" (GB 34) and "Liangqiu" (ST 34) on the left hindlimb for 10 min, 3
      times a week for 3 weeks. Serum MMP-3 and MMP-13 contents were detected with
      enzyme linked immunosorbent assay (ELISA) method. RESULTS: In comparison with
      model group (grade III: 1 case; grade: 4 cases), the left knee-joint-motion range
      of rabbits in acupotomy and EA groups (grade I: 1 and 1 case; grade II: 4 and 3
      cases; grade III: 2 and 2 cases; grade IV: 1 and 2 cases separately) increased
      significantly (P < 0.05). Compared with normal group, serum MMP-3 and MMP-13
      contents in model group increased significantly (P < 0.05); while compared with
      model group, both MMP-3 and MMP-13 levels of acupotomy and EA groups reduced
      considerably (P < 0.05). No obvious difference was found between acupotomy and EA
      groups in the left knee-joint motion range, and serum MMP-3 and MMP-13 levels (P
      > 0.05). CONCLUSION: Acupotomy is effective in lowering serum MMP-3 and MMP-13
      levels, and in improving OA rabbits' knee-joint motion range.

PMID- 19097502
TI  - [Analysis on the difference of afferent mechanism of analgesic signals from
      manual acupuncture and electroacupuncture of "Zusanli" (ST 36)].
AB  - OBJECTIVE: To observe the difference of signaling afferent mechanism of acupoints
      analgesic effect between manual acupuncture (MA) and electroacupuncture (EA) of
      "Zusanli" (ST 36) in order to analyze the initiating mechanism of these two
      commonly used clinic acupuncture methods. METHODS: A total of 64 SD rats were
      randomized into control, model, MA, EA, collagenase (type- I)-pretreatment (CP) +
      MA, CP + EA, disodium cromoglicate-pretreatment (DSCP) + MA and DSCP + EA groups
      with 8 cases in each. Arthritis model was established by intra-joint injection of
      complete Freunds' agent. MA(rotation, 20 min), and EA (21 min) were applied to
      bilateral "Zusanli" (ST 36) respectively in different groups. Pain threshold (PT,
      paw withdraw latency) was detected with 336 GT PAW/TAIL STIMULATOR and
      degranulated mast cells were counted under microscope separately. RESULTS:
      Compared with normal control group, PT values of model, MA, EA, CP + MA, CP + EA,
      DSCP + MA and DSCP + EA groups lowered significantly before treatment (P < 0.05).
      Comparison of the same one group showed that after the treatment, PT values of MA
      and EA groups increased considerably (P < 0.05). PT changing rates of CP + MA and
      DSCP + MA were significantly lower than that of MA group (P < 0.05), suggesting
      disappearance of MA analgesia (not EA analgesia) after lesion of collagen protein
      by CP in ST36 area. In comparison with control group, the degranulation ratios
      (DGR) of mast cells in MA and EA groups increased significantly (P < 0.05); while
      compared with MA and EA groups separately, DGR of the corresponding CP + MA and
      DSCP + MA, and CP + EA and DSCP + EA groups decreased markedly (P < 0.05),
      displaying an inhibition of mast cell degranulation following CP and DSCP in ST36
      area. CONCLUSION: Both MA and EA can induce analgesia and concomitant increase of
      DGR of mast cells. The collagen fibers may contribute to MA initiated analgesic
      effect while the peripheral nerve receptors are probably involved in EA analgesia
      in rat.

PMID- 19097503
TI  - [Effects of acupuncture at "open" or "close" time and in "host" or "guest"
      sequence on uterine contraction in late pregnancy rats].
AB  - OBJECTIVE: To observe the effect of acupuncture at "open" or "close" time and in
      "host" or "guest" sequence on uterine contraction in late pregnancy rats so as to
      explore the regularities of acupoint application. METHODS: A total of 32 pregnant
      rats were divided into "open/host-guest" (OHG) group, "open/guest-host" (OGH)
      group, "close/host-guest" (CHG) group and pregnancy group, with 8 cases in each.
      Eight normal rats were made up of normal control group. According to Ling Gui Ba
      Fa (Eight Laws of Spirit Turtle), acupuncture was given to "Zhaohai" (KI 6),
      "Lieque" (LU 7), "Hegu" (LI 4) and "Sanyin-jiao" (SP 6) first or later
      separately. For example, in OHG group, KI6 (host point, being in opening time)
      was punctured first with the acupuncture needle manipulated for 5 min, then, LU7
      (guest point) punctured and stimulated for 5 min, LI4 (corresponding point of
      KI6) for 20 min, and then, SP6 (another corresponding point) was punctured and
      stimulated for 5 min in order. In CHG group, KI6 (being in closing time) was
      needled for 5 min first, followed by puncturing LU7, LI4 and SP6 for 5 min, 20
      min, and 5 min separately in sequence. The uterine tension and uterine
      contraction frequency were measured by using a tension transducer. RESULTS: In
      comparison with normal control group, uterine smooth muscular tension and
      contraction frequency increased significantly in model group, and after
      acupuncture stimulation in OHG, OGH and CHG groups (P < 0.01, P < 0.05). Compared
      with model group, uterine tension of CHG group was significantly lower in the 8th
      time course after acupuncture (15-20 min after removing acupuncture needle, P <
      0.05). No significant differences were found among model, OHG and OGH groups, and
      among OHG, OGH and CHG groups in uterine tension and contraction frequency (P >
      0.05). CONCLUSION: "Close-host-guest needling" can reduce uterine tension, which
      is likely to have significance in maintaining a stable environment of the uterus
      during pregnancy.

PMID- 19097504
TI  - [Comparison between governor meridian and its bilateral control points in
      microcirculatory blood perfusion in 53 volunteer subjects].
AB  - OBJECTIVE: To observe the difference of the microcirculation blood perfusion
      volume between the Governor Vessel (GV) running course and its bilateral control
      points in healthy volunteers. METHODS: A total of 53 healthy volunteers were
      recruited in the present study. Cutaneous and muscular microvascular blood
      perfusion units (BPU) of Mingmen (GV 4), Jizhong (GV 6), Zhiyang (GV 9), Shenzhu
      (GV 12) and non-acupoint (at the 12th thoracic vertebra level) of GV and their
      bilateral non-meridian points (1 cm lateral to the above mentioned GV-acupoints
      and non-acupoint on both sides) were measured by using a Laser Doppler Flowmetry
      (PeriFlux 5000). RESULTS: 1) In comparison with bilateral control points, the
      cutaneous microvascular BPU values of Mingmen (GV 4), Jizhong (GV 6), Zhiyang (GV
      9), Shenzhu (GV 12) and non-acupoint of GV Meridian were significantly higher (P
      < 0.01). 2) Compared with bilateral control points, BPU values of GV4, GV6, GV9,
      GV12 and non-acupoint of GV Meridian 1 cm, 1.5 cm and 2 cm beneath the skin were
      significantly higher (P < 0.05). No significant differences were found between
      the bilateral corresponding control points of GV4, GV6, GV9, GV12 and non
      acupoint of GV in cutaneous BPU values, and between bilateral control points and
      GV4 in BPU values of deep (2.5 cm beneath the skin) tissues (P > 0.05).
      CONCLUSION: Blood flow perfusion volumes in the skin and deeper tissues along GV
      are significantly higher than those of their bilateral corresponding control
      points, indicating that cutaneous microvascular blood flow and shallower muscular
      blood flow may be the heat source for forming infrared radiation trace along
      meridian (IRRTM) in our past studies.

PMID- 19097505
TI  - [Study on acupoint-like and meridian-like structure of the body surface in
      Cryprinus carpiods].
AB  - OBJECTIVE: To probe into the relationship between receptors on the body surface
      of Cryprinus carpiods and meridians and acupoints of Chinese medicine. METHODS:
      Six Cryprinus carpiods [body length: (4.0 +/- 0.4) cm] purchased from the market
      were put into a glass container filling with 30 micromol/L DiA [4-(4
      Diethylaminostyryl)-N-Methylpyridinium Iodide] water solution for 2 hours and
      then anaesthetized (with 2% aether) for observation under fluorescent microscope.
      Another 6 Cryprinus carpiods [body length: (8.1 +/- 0.6) cm] were put into a pool
      with 30 micromol/L DiA water solution for 7 days and then anaesthetized for
      microscopic observation. RESULTS: 1) The DiA-labeled spots appeared on Cryprinus
      body surface regularly distributing in discontinuous lines, some of them gathered
      together to form clusters. The labeled spots around the eyes distributed in
      radial style and in linear arrangement along the margin of the gill cover. On the
      body trunk, the labeled clusters distributed in linear arrangement along the
      longitudinal axis of the body and formed 14 lines approximately. 2) In Cryprinus
      carpiods fed in water with DiA for 7 days, the labeled receptors clearly showed
      some neuronfibrae. CONCLUSION: The areatus distribution and linear arrangement of
      receptors on the body surface in Cryprinus carpiods are similar to those of
      acupoints and meridians described in the human body in Chinese medicine.

PMID- 19097506
TI  - [Exploitation and application of "acupuncture manipulation information analysis
      system"].
AB  - On the basis of "ATP-I Type Acupuncture Manipulation Parameter Analyzer", we have
      developed a new acupuncture parameter analysis software named "Acupuncture
      Manipulation Information Analysis System" by applying new arithmetic, enriching
      practicable parameters of acupuncture manipulation, and improving the methods for
      comparing and evaluating acupuncture manipulation. The present analysis system
      can satisfy the need of acupuncture manipulation teaching standardization.

PMID- 19097507
TI  - [Effect of long-time retention of scalp needle on the abilities of cognition,
      daily living activity and P300 in vascular dementia patients].
AB  - OBJECTIVE: To observe the curative effect of long-time retention of scalp needle
      in the treatment of vascular dementia (VD) patients, and its influence on P300.
      METHODS: Sixty-five cases of VD patients were randomly divided into acupuncture
      group (n = 33) and medication group (n = 32). For patients of acupuncture group,
      Duxil tablets were taken orally, scalp-points Dingzhongxian (MS 5), Ezhongxian
      (MS 1) and bilateral Dingpangxian I (MS 8) were punctured separately with the
      filiform needles retained for 10 h, once daily for 8 weeks. Patients of
      medication group were asked to take Duxil tablets orally, one tablet/time, twice
      daily for 8 weeks. Mini-mental state examination (MMSE), Hastgawa dementia scale
      (HDS) were used to evaluate the patients' abilities of orientation, calculation,
      immediate and remote memory and speech. Activity of Daily Living (ADL) Scale was
      used to evaluate their daily life ability. The latency and amplitude of event
      related potential P300 of electroencephalograph (EEG) were analyzed before and
      after the treatment. RESULTS: After the treatment, of the 33 and 32 cases in
      acupuncture and medication groups, the controlled, markedly effective, effective
      and ineffective cases were 2 and 1, 9 and 4, 18 and 16, 4 and 11, respectively;
      with the total effective rates being 87.88% and 68.75% separately. The total
      effective rate of acupuncture group was obviously higher than that of medication
      group. Self-comparison showed that MMSE and HDS scores of both acupuncture and
      medication groups increased significantly in comparison with their individual pre
      treatment values (P < 0.05, P < 0.01), while ADL of both groups decreased
      significantly (P < 0.05, P < 0.01). Before treatment, compared with normal
      people, the latencies of P300 in two groups increased significantly (P < 0.01),
      while the amplitudes of two groups decreased significantly (P < 0.01). After the
      treatment, the situations of two groups were corrected apparently (P < 0.05). The
      effects of acupuncture group were significantly superior to those of medication
      group in MMSE, HDS and ADL scores and the latency of P300 (P < 0.05). CONCLUSION:
      Long-term retention of scalp acupuncture needles can improve VD patients'
      intelligence, ADL ability and EEG.

PMID- 19097509
TI  - [An enlightment of the regularities of acupoint indications from acupuncture
      treatment of headache and cardiodynia].
AB  - Analysis on the different styles of expression of acupoint selection and
      application for "Jue Toutong" (severe headache) and "Jue Xintong" (cardiodynia
      with cold limbs) and the development of expression styles of acupoint selection
      and treatment of "Xintong" (cardiodynia) and "Jue Xintong" shows that the
      selected meridians for treatment of the related disorders commonly-seen in the
      ancient acu-moxibustion literature are, in fact, referred to the acupoints on the
      distal part of the four limbs in a certain neurosegment. The closer to the distal
      part of the four limbs, the higher is the identity of the acupoints in
      indications. The limit of the distal part is basically located at the wrist and
      ankle joints. If this identity of acupoint indications is referred to categories
      of diseases or syndromes, the range of acupoints on the four limbs may be
      extended to proximal part of the elbow and knee joints, and the representative
      acupoints are Five Shu-Points (Well-point, Spring-point, Stream-point, River
      point and Sea-point).

PMID- 19097508
TI  - [Comparison of analgesic effects between subcutaneous penetration needling and
      straight needling of otopoints in the treatment of scapulohumeral periarthritis].
AB  - OBJECTIVE: To confirm the better analgesic effect of subcutaneous penetration
      needling of otopoints for treatment of scapulohumeral periarthritis (SHPA)
      patients. METHODS: Sixty-six SHPA patients were randomized into penetration
      needling group (n = 33) and straight needling group (n = 33) by using pairing
      principle according to the sex and state of disease. Penetration needling was
      adopted for patients of penetration-needling group, while straight needling was
      used for those of straight needling group. Simplified McGill Scale was used to
      evaluate the patients' pain reactions. The pain integral scores were analyzed by
      using sequential test and pairing t test. RESULTS: Sequential test showed that
      the analgesic effect of penetration needling was significantly superior to that
      of straight needling 30 min after the treatment (P < 0.05). Pairing t test
      results displayed that penetration needling had a marked analgesic effect 5 min
      and 30 min after the treatment compared with straight needling (P < 0.05).
      CONCLUSION: The rapid analgesic effect of penetration needling is superior to
      that of straight needling in the treatment of scapulohumeral periarthritis.

PMID- 19097510
TI  - [Introduction to Mr CHENG Dan-An and his works].
AB  - Mr CHENG Dan-an is a famous educationist and acupuncturist in modern China. He
      established the earliest acupuncture correspondence institution named Chinese
      Research Society of Acu-moxibustion. Meanwhile he founded the earliest
      professional magazine, Journal of Acu-moxibustion which played an important role
      in promoting redevelopment of acu-moxibustion. Mr CHENG Dan-an wrote many famous
      works. Research on CHENG's academic thoughts and works will help a lot in knowing
      the development and evolution of modern acupuncturology in the period of the
      Republic of China. The present paper introduces it by the help of 7 books
      including Zhenjiu Zhiliao Xue (Chinese Acu-moxibustion Therapeutics).

PMID- 19097511
TI  - [Application of rat's praxiology evaluation to researches on the mechanism of
      acupuncture in the treatment of some diseases].
AB  - The present paper reviews recent progress about the application of rat's
      praxiology evaluation in studies on the mechanism of acupuncture in the treatment
      of some diseases from 1) motor functional impairment evaluation; 2) cognition
      impairment evaluation; 3) animal mood score, and 4) pain behavior evaluation. By
      using different praxiology evaluation methods, the acupuncture curative effect
      has been confirmed repeatedly in different pathological models. The animal
      experimental study plays an important role in understanding the mechanisms of
      acupuncture in the treatment of some common diseases in clinic. However, due to
      the multiplicity of diseases, and specificity of various phases of a disease,
      extensive and specific behavior evaluation methods are relatively fewer, some
      current method terms are still obscure and manual of operations is deficient.
      Therefore, further improvement of the current behavior evaluation methods and
      developing more methods with stronger and specific functions aiming at different
      experiments (disease models) are definitely necessary.

PMID- 19097512
TI  - [Synopsis about the hypothesis of "information channel" of channel-collateral
      system].
AB  - The author of the present paper founded a theorem about the "incompleteness of
      single channel structure" (nerve, blood vessel, lymphatic, interspace, aperture,
      etc.) through quantitative and qualitative analysis about the economic
      information channel in the human body, which eliminates the probability of single
      channel structure in the information channel of channel (meridian)-collateral
      system. After comprehensive analysis on the current researches, the author puts
      forward a neodoxy, i.e., the body "information channel" structure of the channel
      collateral system, mainly follows the distribution regularity of systemic
      statistics, and is not a single specific entity; various layers of the
      information channel in the main stems of the channel-collaterals are composed of
      optimized structure tissues. Hence, the structure of this information channel of
      channel-collateral system is an overall-optimized, sequential and compatible
      systemic structure. From this neodoxy, the author brings forward a working
      principle of channel-collaterals, which is supported theoretically by bio
      auxology. The longitudinal distribution of the main stems of meridian-collaterals
      is considered to result from that in the process of the animal evolution, in the
      animals moving forward, the microscopic complicated movement of intracorporeal
      information and energy molecules is related to the forward macroscopic and non
      uniform movement of organism in trans-measure. Its impulse and kinetic momentum
      forms a main vector in the longitudinal direction of the body (the direction of
      the main stem of channel-collaterals). In order to adapt to and utilize natural
      regularities, the main stems of the channel-collaterals gradually differentiate
      and evolve in the living organism, forming a whole system. The "hypothesis of
      biological origin of channel-collateral system" and "that of information channel
      of the channel-collaterals in the body" constitute a relatively complete
      theoretical system framework.

PMID- 19097513
TI  - Vaginal fluid human chorionic gonadotropin for detection of rupture of membranes.
AB  - OBJECTIVE: To evaluate the accuracy of qualitative and quantitative human
      chorionic gonadotropin (hCG) assays to detect ruptured amniotic membranes (ROM)
      in term patients. STUDY DESIGN: We conducted a prospective cohort study enrolling
      100 term pregnancies with intact membranes. Samples were collected before and
      immediately following ROM, and at 2 and 4 hours post-ROM. Quantitative and
      qualitative hCG assays were performed on all samples. Outcome measures included
      the detection and measured amount of hCG before and after ROM. Sensitivity,
      specificity and positive predictive values for the qualitative assays were
      determined. RESULTS: A total of 98% pre-ROM and 100% post-ROM qualitative assays
      tested positive with mean quantitative hCG levels of 181.30 mIU/mL and 208.24
      mIU/mL, respectively. The qualitative post-ROM sensitivity was 100%; however, the
      pre-ROM specificity was only 2%. The positive predictive value for detecting ROM
      was 50%. CONCLUSION: Qualitative and quantitative hCG assays are not useful for
      determining ROM in term pregnancies.

PMID- 19097514
TI  - Utility of in-office endometrial ablation: a prospective cohort study of
      endometrial ablation under local anesthesia.
AB  - OBJECTIVE: To determine tolerability of in-office endometrial ablation under
      local anesthesia and the rate of adverse events in the first 2 postoperative
      weeks. STUDY DESIGN: The study was a prospective cohort single group study.
      RESULTS: Ablation was performed on 148 patients under deep parametrial block
      using dilute mepivacaine and oral anxiolysis. No patient requested the procedure
      be stopped due to pain, but 1 requested intraoperative reinjection of anesthetic.
      No patient required admission due to pain. No serious adverse events were noted
      intraoperatively or in the first 2 weeks following the procedure. The most common
      adverse event at follow-up was bacterial vaginosis in 16 of 143 (11%) of the
      evaluable cohort. Five patients were seen after the first 2 weeks, without
      complications, but were therefore excluded from the study. Patient satisfaction
      was assessed at 2-week follow-up visit in the 143 evaluable cohort. A total of
      130 of 143 patients (90%) reported being "Very Satisfied", 13 (9.1%) reported
      being "Satisfied" and none were "Unsatisfied". CONCLUSION: Endometrial ablation
      can be performed successfully in the physician's office under local anesthesia
      and oral anxiolysis with low patient pain scores, high tolerability and high
      patient satisfaction. Serious adverse events were not encountered when performed
      by properly trained practitioners.

PMID- 19097515
TI  - Contemporary approaches to cystocele repair: a survey of AUGS members.
AB  - INTRODUCTION: To assess practice patterns in the management of cystoceles among
      American Urogynecologic Society (AUGS) members. STUDY DESIGN: A 22-question
      survey regarding various cystocele repair techniques was delivered to AUGS
      members via e-mail. RESULTS: Of 963 members surveyed, there were 315 respondents.
      For the treatment of primary cystocele, 77% of respondents used midline vaginal
      plication; 40% used this approach for management of recurrent cystocele. At the
      time of abdominal sacrocolpopexy, most considered the anterior vaginal graft
      sufficient to address cystocele. At the time of uterosacral suspension, midline
      plication was the most common approach to address cystocele. The most commonly
      used graft material was synthetic mesh (67%). Almost half of respondents used
      minimally invasive transobturator devices for cystocele repair. CONCLUSION: The
      wide variety of surgical approaches likely reflects the absence of a clearly
      defined best practice for cystocele repair, underscoring the need for rigorous
      surgical trials.

PMID- 19097516
TI  - Communicating with women about menstrual cycle symptoms.
AB  - Eighty-five percent of reproductive-aged women experience physical or emotional
      changes with their menstrual cycle. Up to 40% of women are bothered by menstrual
      cycle-related symptoms and conditions, such as dysmenorrhea, premenstrual
      syndrome (PMS) and premenstrual dysphoric disorder (PMDD). These conditions
      influence women's lives, relationships and work. Dysmenorrhea is the most common
      reason for absenteeism for women younger than age 30, yet many do not discuss
      this with their clinicians despite potential treatment options that include
      selective serotonin reuptake inhibitors (SSRIs), nonsteroidal anti-inflammatory
      drugs (NSAIDs), certain oral contraceptives used continuously or intermittently,
      cycle ablation medicines and anxiolytics. Effective treatment of cyclic symptoms
      hinges on effective doctor-patient communication. Patients who report that their
      health care providers converse with them and engage them in decision making
      obtain more relief and are more satisfied with their health care. Given the
      frequency of symptoms and the availability of treatment options, health care
      providers should remember to routinely ask questions about cycle-related
      symptoms. This will encourage patients to provide information and to participate
      in the management of these symptoms, thus improving their productivity and
      quality of life.

PMID- 19097517
TI  - Evaluation of compliance and range of fees among American Society for
      Reproductive Medicine-listed egg donor and surrogacy agencies.
AB  - OBJECTIVE: To evaluate the compliance of donor and surrogacy agencies to American
      Society for Reproductive Medicine (ASRM) guidelines and assess regional
      differences in agency, donor, and surrogacy fees in the United States. METHODS: A
      retrospective study was performed of websites from agencies that have signed an
      agreement with the Society for Reproductive Technology (SART) to abide by ASRM
      guidelines in governing egg donor prices and surrogacy compensation. RESULTS: A
      total of 66 agencies are listed on the website, divided into 8 national regions;
      24.5% of egg donor agencies deviated from ASRM guidelines. There was no
      significant difference in the agency fees among the different regions of United
      States, but the agency fees for egg donation trend higher in the west.
      CONCLUSION: A substantial number of egg donor agencies in the United States are
      not abiding by the ASRM guidelines. Oversight may be needed to correct improper
      marketing practices for egg donor recruitment.

PMID- 19097519
TI  - Spousal military deployment as a risk factor for postpartum depression.
AB  - OBJECTIVE: To compare the Edinburgh Postnatal Depression Scale (EPDS) results in
      women whose spouses had deployed during or after pregnancy vs. those whose
      spouses had not. STUDY DESIGN: A chart review of 6-week postpartum visits of
      women with active-duty spouses was conducted over 10 months. Associations between
      military deployments and EPDS score were examined by Student's t test, and rates
      of positive screens (with a cutoff of 12) between groups were compared by odds
      ratio (OR). Linear regression was used to calculate predictors of EPDS score.
      RESULTS: A total of 415 charts were analyzed. The average EPDS score of women
      whose partner did deploy during the pregnancy was 7.36 compared to 4.81 for those
      whose partners did not (p < 0.001). The percentage of positive screens for women
      whose partner deployed during the pregnancy was 25.27% compared with 10.94% for
      an OR of 2.75 (p < 0.001). Linear regression showed partner's deployment during
      pregnancy to be an independent predictor of EPDS score (p < 0.005). CONCLUSION:
      Deployment of a spouse during pregnancy may be a risk factor for depression.
      Aggressive screening of this at-risk population is recommended.

PMID- 19097518
TI  - Interleukin-18 gene promoter polymorphisms in women with gestational
      trophoblastic diseases.
AB  - OBJECTIVE: Gestational trophoblastic diseases (GTDs) consist of a spectrum of
      disorders characterized by an abnormal proliferation of trophoblastic tissue. IL
      18 is a pleiotropic cytokine with a capacity for both ThI and Th2 polarization.
      Considering the association of IL-18 promoter polymorphisms at positions -607
      (A/C) and -137 (C/G) with pregnancy events and some cancers, we sought to examine
      these polymorphisms in Iranian patients with GTD, their association with disease
      subtypes, and IL-18 serum level. STUDY DESIGN: Single nucleotide polymorphisms
      (SNPs) were analyzed by allele-specific polymerase chain reaction in 92 patients
      with GTDs and 103 healthy pregnant controls. IL-18 serum level was determined
      using ELISA method. RESULTS: No significant association was found between the
      allele, genotype, genotype combination and haplotype distribution of these SNPs
      and GTDs or its subgroups. Mean IL-18 serum level was significantly higher in
      patients with choriocarcinoma and pregnant controls compared with nonpregnant
      controls (p = 0.04, 0.04 and 0.001, respectively). -137 GG genotype pregnant
      controls had a significantly higher IL-18 serum level compared with CC genotype.
      CONCLUSION: IL-18 promoter polymorphisms do not confer susceptibility to GTDs or
      its variants; however, their functional significance is demonstrated in this
      study. Furthermore, IL-18 serum level increases in GTDs and in normal pregnancy.

PMID- 19097520
TI  - Characteristic sonographic vesicular pattern of a complete hydatidiform mole in
      the early first trimester.
AB  - OBJECTIVE: To evaluate the sonographic vesicular pattern of a complete
      hydatidiform mole (CHM) in the early first trimester. STUDY DESIGN: A
      retrospective study was performed on 30 cases of histologically proven CHMs in
      the early first trimester. Two radiologists reviewed the sonograms of all cases
      before evacuation and determined the extent of vesicular pattern for each case
      independently. The extent of vesicular area was divided into 4 categories:
      absent, mild (less than one third), moderate (one third to two thirds) or severe
      (more than two thirds). Interobserver agreement between the reviewers was
      calculated by weighted kappa. RESULTS: The mean gestational age of all cases at
      ultrasound was 7.6 +/- 2.0 weeks (mean +/- SD) with a range of 5.0-12.5 weeks.
      Reviewer 1 classified the extent of sonographic vesicular pattern as absent
      (10%), mild (63.3%), moderate (20%) and severe (6.7%). Reviewer 2 classified the
      cases as absent (10%), mild (53.3%), moderate (33.3%) and severe (3.3%). There
      was almost perfect agreement in categorizing the vesicular pattern between the
      reviewers (kappa = 0.866). CONCLUSION: A mild sonographic vesicular pattern of
      CHM was common in the early first trimester.

PMID- 19097521
TI  - Absence of progesterone receptors in a failed case of fertility-sparing treatment
      in early endometrial cancer: a case report.
AB  - BACKGROUND: Fertility-sparing treatment may be offered as an alternative to
      standard surgical management of early-stage, well-differentiated endometrial
      cancer in young women. Immunostaining for progesterone receptor (PR) status is
      not currently part of the standard workup before treatment recommendations are
      made. CASE: We describe a 29-year-old woman who used oral contraceptive pills on
      a long-term basis in whom early-stage, well-differentiated endometrial cancer was
      diagnosed. Progestin therapy failed and the tumor was subsequently found to be PR
      negative. CONCLUSION: Combination oral contraceptive pills may stimulate clonal
      expansion of endometrial cells that lack PR, leading to endometrial
      adenocarcinoma unresponsive to progestin therapy. Consideration should be given
      to PR immunostaining for confirmation of the receptor status and evaluation of
      appropriate management options when counseling patients about fertility-sparing
      therapy.

PMID- 19097522
TI  - Bartholin abscess masquerading as an unusual vaginal prolapse: a case report.
AB  - BACKGROUND: Vaginal wall cysts and pelvic organ prolapse, although commonly
      encountered, rarely occur together. Typically, the differential diagnosis of
      vaginal wall prolapse includes anterior and/or posterior wall support defects.
      Although large vaginal cysts have the potential to disturb normal vaginal
      supports, these coexisting abnormalities are rarely reported. CASE: A 39-year-old
      multipara woman presented with a progressively enlarging vaginal bulge for 6
      years, erroneously diagnosed as an enterocele with a unilateral paravaginal
      support defect. The enterocele was subsequently confirmed to be a 10 x 5-cm,
      thick-walled cystic mass histologically confirmed to be a Bartholin gland
      abscess. CONCLUSION: Unusual forms of vaginal prolapse require adequate ancillary
      investigation such as imaging to avoid diagnostic error and to improve
      preoperative planning and treatment.

PMID- 19097523
TI  - Endometrial osseous metaplasia mimicking retained intrauterine device: a case
      report.
AB  - BACKGROUND: Osseous metaplasia of the endometrium is a rare disorder and can be
      associated with infertility. Although successful diagnosis and treatment have
      been widely reported, correct diagnosis in many cases still represents a
      challenge. CASE: A 40-year-old woman complaining of infertility presented with a
      diagnosis of retained intrauterine device (IUD) on ultrasound. Hysteroscopy
      revealed a normal endometrial cavity, but no IUD was visualized. Curettage
      pathology specimens showed chronic endometritis and calcification. Repeat
      hysteroscopy was performed because of persistent echogenic foci in the
      endometrium on follow-up ultrasound. Several irregular and calcified plaques were
      successfully removed. CONCLUSION: Osseous metaplasia can be misdiagnosed because
      of its rare incidence. Physicians should be aware of osseous metaplasia in the
      differential diagnosis of patients with uncertain history who present with a
      sonographic image resembling an IUD.

PMID- 19097524
TI  - Abdominal wall endometrioma following cesarean delivery: a case report.
AB  - BACKGROUND: Rarely, endometriosis occurs in an abdominal wall scar after a
      cesarean delivery. CASE: This case report summarizes the presentation, diagnosis
      and treatment of a woman with an abdominal wall endometrioma within a cesarean
      delivery skin incision scar. CONCLUSION: An abdominal wall endometrioma needs to
      be considered in the differential diagnosis of any woman of reproductive age
      presenting with a painful abdominal wall mass and a history of uterine surgery
      via an abdominal incision.

PMID- 19097525
TI  - Pancreatic trauma: demographics, diagnosis, and management.
AB  - Pancreatic injuries are rare, with penetrating mechanisms being causative in
      majority of cases. They can create major diagnostic and therapeutic challenges
      and require multiple diagnostic modalities, including multislice high-definition
      computed tomography, magnetic resonance cholangiopancreatography, endoscopic
      retrograde cholangiopancreatography, ultrasonography, and at times, surgery and
      direct visualization of the pancreas. Pancreatic trauma is frequently associated
      with duodenal and other severe vascular and visceral injuries. Mortality is high
      and usually related to the concomitant vascular injury. Surgical management of
      pancreatic and pancreatic-duodenal trauma is challenging, and multiple surgical
      approaches and techniques have been described, up to and including pancreatic
      damage control and later resection and reconstruction. Wide surgical drainage is
      a key to any surgical trauma technique and access for enteral nutrition, or
      occasionally parenteral nutrition, are important adjuncts. Morbidity associated
      with pancreatic trauma is high and can be quite severe. Treatment of pancreatic
      trauma-related complications often requires a combination of interventional,
      endoscopic, and surgical approaches.

PMID- 19097526
TI  - Incidental pulmonary embolism identified on chest CT during initial trauma
      evaluation.
AB  - Deep venous thrombosis and pulmonary embolism frequently occur after trauma and
      continue to account for significant morbidity and mortality in this population.
      Asymptomatic pulmonary emboli are also believed to be quite common, but the
      incidence as well as the implications of these events is unknown. This case
      report describes two patients whose pulmonary emboli were found incidentally on
      the initial trauma workup. Very little has been written concerning this issue and
      in this case report we review the risk factors and clinical significance of these
      "incidentally discovered" pulmonary emboli.

PMID- 19097527
TI  - Does fever at the time of discharge have any impact on the incidence of
      readmission?
AB  - Most physicians believe that patients who have fever within 24 hours of the
      planned date of discharge should be kept in the hospital until the fever
      resolves. A search of the literature revealed very few articles addressing this
      topic. The object of this study was to review a number of patient discharges from
      the surgical service and to document the presence or absence of fever within 24
      hours of the time of discharge. The primary end point of the study was to
      determine the rate of readmission for both patients discharged with fever and
      those discharged without fever. Secondary end points were to determine whether
      the readmission was related to the original discharge diagnosis or the presence
      of fever at the time of discharge. The records of all adult patients with a
      hospital length of stay of > or = 5 days discharged from the surgical and
      gynecology services from April through July of 2007 were reviewed. Deaths were
      excluded. The following data elements were recorded: primary discharge diagnosis;
      age; highest recorded temperature within 24 hours of discharge; date time and
      cause of readmission within 30 days; and outcome. Fever was defined as a
      temperature of > or = 100 degrees F. Data were entered into an Excel (Microsoft,
      Redmond, WA) spreadsheet, and statistical analysis was performed using chi2 and
      Fisher's exact tests using Primer of Biostatistics (McGraw-Hill, New York, NY).
      The records of 300 consecutive patients were reviewed. Follow-up was available
      for 86.7 per cent of the patients, 84.4 per cent of the febrile patients, and
      87.1 per cent of the nonfebrile patients. A fever of > or = 100 degrees within 24
      hours of discharge was noted in 45 (15.0%) patients. The mean fever was 100.5
      degrees, with a range of 100 degrees to 102.1 degrees. There were 38
      readmissions. Of the 45 patients with fever, seven (15.6%) were readmitted. Of
      those seven, four readmissions were related to the previous admitting diagnosis.
      Of the patients who were discharged without fever, 31 (12.2%) were readmitted
      with 24 of those readmissions for diagnoses related to the first admission. The
      rate of readmission for fever and nonfever patients was not statistically
      significantly different (P = 0.697). Similarly, the rate of related versus
      nonrelated diagnoses in both the fever and nonfever groups was not statistically
      significantly different (P = 0.351). The presence or absence of fever within 24
      hours of patient discharge seems to have no impact on the rate of readmission
      within 30 days.

PMID- 19097528
TI  - Fistulogram after arteriovenous dialysis graft thrombectomy should be mandatory.
AB  - The purpose of this study was to determine if fistulogram after prosthetic
      arteriovenous dialysis graft thrombectomy would reveal underlying lesions, which
      need correction, and if revision would improve graft patency. One hundred and
      ninety-two open thrombectomy procedures in 61 patients from January 1, 2000 to
      July 31, 2005 were reviewed retrospectively. All of the study patients were
      divided into two groups: In Group I fistulogram was carried out and in Group II
      no fistulogram was performed. Based on the fistulogram or clinical findings,
      appropriate intervention was carried out. In Group I, of 99 thrombectomy
      procedures, a significant lesion was identified and revision was carried out in
      77 cases (78%). In Group II, of 93 thrombectomy procedures, a significant lesion
      was identified and revised in 53 cases (57%). A significant abnormality was more
      likely to be encountered by routine fistulogram than surgical exploration alone,
      78 per cent versus 57 per cent (P < 0.05). Assisted primary patency is
      significantly increased in Group I and II when revision was performed (4.84
      months) compared with when no fistulogram and no revision was performed (2.9
      months), P < 0.05. Routine fistulogram after thrombectomy of an arteriovenous
      dialysis graft increases the likelihood of identifying a significant stenosis.
      Revision of the graft increases the longevity. We recommend routine use of
      fistulogram during thrombectomy.

PMID- 19097529
TI  - Current evidence based guidelines for factor VIIa use in trauma: the good, the
      bad, and the ugly.
AB  - Recombinant factor VII (rFVIIa) has arisen as an option for the control of life
      threatening traumatic bleeding unresponsive to other means. The timing of
      administration, dosage, mortality, units of blood transfusion saved, risk of
      thrombotic events, and risk/benefits ratio are presently poorly defined. A
      Medline search from 1995 through March 2008 was conducted. All English language
      articles containing the terms "trauma" and "factor VII" or its variants were
      retrieved. Letters to the editor, animal studies, and general reviews were
      excluded. A total of 19 articles met inclusion criteria. These articles were then
      reviewed and stratified into three classes of evidence according to the quality
      assessment instrument developed by the Brain and Trauma Foundation. Levels of
      recommendation were developed. A total of 118 articles were identified. Only one
      Class I study was identified. This study demonstrated that three doses of rFVIIa
      given in blunt traumatic hemorrhage yielded a significant reduction of 2.6 of red
      blood cells used. These findings were not statistically significant for
      penetrating trauma patients. There was no reduction in mortality and no increase
      in thromboembolic events. Four Class II studies were identified; three showed a
      significant decrease of blood product usage and one demonstrated significant
      reductions in 24-hour and 30 day death from hemorrhage in patients receiving
      rFVIIa. The remaining 14 studies were Class III reviews of databases, registries,
      case series, and case reports. No identified study specifically addressed the
      cost/benefit analysis of rFVIIa usage in trauma hemorrhage. Utility of rFVIIa in
      trauma-associated hemorrhage remains controversial. There is Level I supporting
      the use of rFVIIa for blunt trauma patients only. There is no Class I evidence
      supporting decreased mortality or differences in thromboembolic events. Minimal
      effective dosing regimens and cost/benefit analyses have not yet been examined.

PMID- 19097530
TI  - The role of laparoscopy in trauma: a ten-year review of diagnosis and
      therapeutics.
AB  - Minimally invasive surgery has found many applications in general surgery. The
      role of laparoscopy in trauma has been debated as a diagnostic, as well as
      therapeutic, tool in hemodynamically stable patients. This study evaluated
      laparoscopy in the trauma population. A retrospective review of all laparoscopies
      performed in hemodynamically stable trauma patients from 1996 until 2006 was
      conducted. Mechanisms of injury, perioperative data, and demographic variables
      were analyzed using descriptive statistics and Student's t test. Exploratory
      diagnostic laparoscopy was performed on 102 patients. Laparoscopy was negative
      for 65 per cent of patients; 12 per cent of these were converted to laparotomy
      due to adhesions, hemoperitoneum, or surgeon preference. None of the conversions
      revealed intra-abdominal injury at laparotomy. An injury was diagnosed at
      laparoscopy in the remaining 35 per cent, with 55 per cent conversion rate to
      repair the injury. Therapeutic laparoscopy included serosal repair, hemorrhage
      control, diaphragmatic repair, and other standard laparoscopic treatments. No
      patient required re-exploration, there were no missed injuries or other
      complications, and no patient died in this study. Laparoscopy has an important
      diagnostic and therapeutic role in selected hemodynamically stable trauma
      patients. Using a minimally invasive approach can reduce the potential morbidity
      of negative laparotomy.

PMID- 19097531
TI  - Surgical management of cervical paragangliomas.
AB  - Carotid body tumors are rare, but represent the most common form of head and neck
      paraganglioma. We present 17 surgically treated patients. The present study
      reviews our experience in the diagnosis and treatment of these uncommon lesions.
      At surgery, 11 tumors were classified as Shamblin Class II and six as Class III.
      A cerebral angiogram was obtained in all cases before surgery. A cervical
      approach was the method of choice in 16 cases; in one case with mediastinal
      extension of the tumor we used a combined cervical and transsternal approach.
      Complete excision of the tumor was accomplished in all cases. Subadventitial
      tumor excision was performed in eight cases whereas internal carotid artery
      reconstruction was obtained in eight cases (three saphenous interposition vein
      grafts, two polytetrafluoroethylene (PTFE) 6 mm grafts, and end-to-end
      anastomosis in three cases). Resection of the left common carotid artery and
      reconstruction with a Dacron 8 mm graft was performed in the case with
      mediastinal tumor extension. Duplex scan along with angiography is effective in
      making the diagnosis. Excision is indicated for most tumors, and best results are
      achieved by an experienced vascular surgeon.

PMID- 19097532
TI  - Hidradenitis suppurativa complicated by squamous cell carcinoma.
AB  - Hidradenitis suppurativa (HS) is a chronic inflammatory condition affecting the
      apocrine glands of the axilla, groin, and perianal region. Although it is a
      common condition, it is rarely associated with squamous cell carcinoma (SCC).
      There have been only 41 reports of this uncommon complication of HS in the
      literature. This study includes two uncommon presentations of HS associated with
      SCC along with a literature review. The first patient developed diffuse abdominal
      carcinomatosis from SCC in the anogenital region arising from HS. This is a rare
      event in patients with perianal SCC, with only one case previously described in
      the literature. The second patient developed malignant hypercalcemia, an uncommon
      complication of cutaneous SCC. The current report represents the largest review
      of the literature of patients with SCC secondary to longstanding HS. A recurrence
      rate of 48 per cent was observed after "curative" resection. Approximately half
      of the patients succumbed to their disease, and the grade of carcinoma was the
      only predictor of mortality. These two new cases underline the importance of
      close follow-up and aggressive management of patients with HS. Although the
      development of carcinoma is an uncommon event in HS, the consequences can be
      devastating with mortality approaching 50 per cent.

PMID- 19097533
TI  - The cuff leak test is not predictive of successful extubation.
AB  - In intubated patients the presence of a cuff leak (CL) is used as a predictor of
      successful extubation. CL is proposed to indicate laryngeal edema and predict
      which patients may develop complications such as postextubation stridor and
      eventual reintubation. Our objective was to evaluate the reliability of CL in our
      population of critically ill trauma patients. A retrospective chart review was
      performed of patients admitted to the trauma service who required mechanical
      ventilation. All patients undergo the CL test by a single respiratory therapist
      team before attempted extubation. Data collected included body mass index (BMI),
      endotracheal tube (ETT) size, length of time of mechanical ventilation, tidal
      volumes (Vt), and the size of the patient's trachea based on CT scan. The test is
      performed by the respiratory therapists and involves measuring expired Vt before
      and after the ETT cuff has been deflated and listening for an audible leak. A
      positive test result is defined as a CL greater than 10 per cent of Vt or, when
      volumes are not available, as audible air expired. From October 2005 to May 2006,
      150 mechanically ventilated patients were identified and 49 charts were available
      for review. Forty-one patients had a cuff leak (+CL), whereas eight did not (
      CL). The two cohorts were similar in age (+CL = 36.5 years, -CL = 38.1 years, P =
      0.82), male gender (+CL = 70%, -CL = 50%, P = 0.25) ETT size (+CL = 7.4, -CL =
      7.4, P = 0.57), and BMI (+CL = 28 kg/m2, -CL = 27 kg/m2, P = 0.71). The average
      tracheal diameter (+CL = 17.4 mm, -CL = 17.5 mm, P = 0.90) as well as the ratio
      of ETT and tracheal diameter was similar for the two cohorts (+CL = 0.65, -CL =
      0.64, P = 0.73). Four patients (10%) in the +CL cohort failed extubation, whereas
      none of the -CL cohort failed (0%) (P = 0.40). The CL test does not reliably
      identify those patients who will require reintubation in our trauma population.
      In addition, the ratio of ETT and tracheal diameter is not predictive of
      successful extubation.

PMID- 19097534
TI  - Is endoscopic resection of gastric gastrointestinal stromal tumors safe?
AB  - Gastric gastrointestinal stromal tumors (GIST) commonly present as an incidental
      finding on upper gastrointestinal endoscopy. Advances in endoscopic technology
      have allowed some to perform attempted excision of these lesions endoscopically.
      The oncologic implications of such an approach remain unclear. A-74-year-old man
      initially presented with an incidental finding of a 1.6 x 1.8-cm c-kit-positive
      gastrointestinal stromal tumor with low mitotic activity in the gastric fundus.
      The patient underwent an attempted endoscopic resection of this mass resulting in
      incomplete excision and gastric perforation. There was immediate conversion to a
      celiotomy and the patient underwent partial gastrectomy; there was no evidence of
      metastatic GIST. Three years later, the patient was noted to have an asymptomatic
      large pelvic mass (4 x 7 cm) on CT scan and was referred for evaluation.
      Subsequent surgical exploration revealed a single mass adherent to the pelvic
      sidewall that was resected. Subsequent pathology demonstrated a c-kit-positive
      GIST consistent with metastatic disease. Eighteen months later, the patient
      remains free of disease. Complications from endoscopic resection of gastric GIST
      may be associated with peritoneal dissemination of disease. This should be
      considered when formulating a strategy for management of gastric GIST. Complete
      transperitoneal excision (either open or laparoscopic) with clear margins and
      without tumor rupture remains the gold standard for management of gastric GIST.

PMID- 19097535
TI  - Proposal for classification of the circumaortic renal collar's morphology.
AB  - In the present study, we propose a classification of the different forms of the
      circumaortic renal collar based on the findings of 319 patients and on a
      literature review. The patients underwent a CT angiography scan of the abdomen
      for various diagnostic reasons. The different forms in which the circumaortic
      renal collar may appear were categorized. The renal collar was observed in eight
      of the 319 (2.5%) patients. The classification we propose is the following: Type
      I, one left renal vein splitting into two branches, a preaortic and a
      retroaortic, draining into the inferior vena cava; Type II, two different left
      renal veins, the one preaortic and the other retroaortic, draining into the
      inferior vena cava; and Type III, either anastomoses between the preaortic and
      retroaortic vein, being multiple or not, or multiple preaortic or retroaortic
      renal veins without anastomoses. Although the circumaortic renal collar is
      usually asymptomatic, the knowledge of this variation is useful, mainly before
      abdominal aortic aneurysm surgery and renal transplantation. Failure to recognize
      the collar's retroaortic component may lead to hemorrhage and death during
      retroperitoneal surgery. We believe that our classification contributes to
      recognize the circumaortic renal collar's morphology both preoperatively and
      intraoperatively.

PMID- 19097537
TI  - Endovascular aortic crossclamp: a novel way to reduce warm ischemia time in DCD
      donors.
AB  - Strategies like donation after cardiac death (DCD) have become more widely
      accepted to increase potential organ supply and decrease waiting list time. Warm
      ischemia time (WIT) is a key prognostic factor for organ function. Any process
      that can decrease WIT could decrease the number of discarded organs as well as
      improve graft and patient survival. A novel endovascular aortic crossclamping
      technique in DCD donors is described. Six kidneys and two livers were recovered
      from three donors. Mean WIT from extubation to aortic crossclamp was 25 +/- 8
      minutes. Time from initial glidewire placement to crossclamp was less than 2
      minutes. All the organs were adequately flushed; back table examination confirmed
      clean venous effluent and no signs of thrombosis. Four kidneys were transplanted.
      Two kidneys were discarded after DCD was prolonged and WIT was 60 minutes. The
      two livers were not allocated. The WIT can be manipulated after cardiac activity
      has stopped. The endovascular crossclamp is a novel and feasible technique that
      can decrease WIT after cardiac death by reducing the surgical time to aortic
      crossclamp.

PMID- 19097536
TI  - Early thrombosis of the superior vena cava in a patient with a central venous
      catheter and carcinoma of the ampulla of Vater.
AB  - Superior vena cava syndrome results from obstruction of flow through the vessel
      either by external compression or thrombosis. External compression by
      intrathoracic neoplasms is the most common etiology. Thrombosis of the vessel
      most often occurs in the setting of indwelling catheters or pacemakers. The
      diagnosis is suggested by the clinical manifestations of facial and upper
      extremity swelling, dyspnea, and cough. It is confirmed by CT scan showing the
      development of collateral flow around the lesion. In this report, we present a
      patient who developed superior vena cava thrombosis after undergoing a short
      period of central venous catheterization and a Whipple procedure for
      adenocarcinoma of the ampulla of Vater. The endothelial damage caused by the
      catheter, the low-flow state induced by the large fluid shifts during the
      operation, and the hypercoagulable state induced by malignancy fulfill Virchow's
      triad for venous thrombosis. To our knowledge, this is the first reported case of
      superior vena cava syndrome after the Whipple procedure with symptoms appearing
      after a shorter period of catheterization than previously reported in the adult
      literature.

PMID- 19097538
TI  - Retroperitoneal mixed-type liposarcoma showing features of four different
      subtypes.
AB  - Mixed-type liposarcoma is a rare soft tissue tumor. This report describes a 50
      year-old man with retroperitoneal mixed-type liposarcoma that consisted of four
      pathologically different components. Preoperative CT and MRI showed a giant
      retroperitoneal mass composed of several nodules with various attenuation and
      signal intensity. At laparotomy, the tumor appeared to be composed of four
      components. Pathologic examination revealed that each component was of a
      histologically different subtype. Mixed-type liposarcoma containing four
      different subtypes is extremely rare. Its clinical and pathologic features are
      briefly reviewed.

PMID- 19097539
TI  - 23-hour stay outcomes for laparoscopic Roux-en-Y gastric bypass in a small,
      teaching community hospital.
AB  - The goal of every surgery is a successful outcome with the shortest hospital
      stay. Morbidly obese patients with their myriad of comorbidities have confounded
      surgeons over the years, usually leading to an increased length of hospital stays
      after complicated surgeries. Laparoscopic Roux-en-Y gastric bypass (LRYGB) has
      proven to be an effective treatment for the morbidly obese with a usual length of
      stay of 3 days. The purpose of this article is to review our experience with 23
      hour stays for LRYGB over a 13-month period and to apply a recently published
      risk score to these patients. A single surgeon performed 173 bariatric surgeries
      of which 96 were LRYGB, the study group. The demographics of this group found the
      overwhelming majority were female, white, slightly older than the men but with a
      somewhat smaller body mass index (BMI). The ethnic breakdown was 67.7 per cent
      white, 22.9 per cent black, and 9.4 per cent Hispanic. The average for all
      patients was 41.7 years and the BMI was 49.25 kg/m2. Using the Obesity Surgery
      Mortality Risk Score, 62.5 per cent of our patients were low risk or Class A,
      37.5 per cent intermediate risk or Class B, and none of our patients qualified as
      high risk or Class C. Our average patient score was 1.3. In terms of length of
      stay, 91 of the 96 patients (94.8%) were discharged within 23 hours of surgery
      without mortality or 30-day readmission. The remaining five patients (5.2%) had
      unexplained, sustained tachycardia and were re-explored on the first
      postoperative day laparoscopically. Three of these patients had negative
      explorations. One had a jejunojejunostomy revision and the other was found to
      have a small bowel injury, which was laparoscopically repaired. All five patients
      were discharged within the next 23 hours. All patients were discharged on a clear
      liquid diet and advanced to a regular diet over the next month. No diet
      intolerance was noted nor were any patients converted to an open operation. In
      conclusion, we have demonstrated that a comprehensive bariatric program in a
      small teaching community hospital can successfully perform LRYGB and discharge a
      high percentage of patients within 23 hours with a very low complication rate. We
      also believe the Obesity Surgery Mortality Risk Score will help bariatric
      programs to risk-stratify their patients preoperatively. This will contribute to
      decision-making and further inform patients of their risk as part of their
      education preoperatively.

PMID- 19097540
TI  - Tumoral pseudoangiomatous stromal hyperplasia of the breast.
AB  - Tumoral pseudoangiomatous stromal hyperplasia (PASH) is a rare benign
      proliferative disease of the breast. The majority of the literature reports of
      PASH have not contained detailed descriptions of the imaging characteristics of
      PASH. A 10-year retrospective study of patients with tumoral PASH and a 20-year
      Ovid MEDLINE search were performed to determine whether specific imaging and
      needle biopsy results could characterize PASH preoperatively. We identified 22
      patients with tumoral PASH. Seventeen (77%) of 22 women had a palpable lump and
      14 (72%) of 21 had a density on mammography. Ultrasound (US) findings included
      mixed or hypoechoic echogenicity in 83 per cent and ill-defined borders in 62 per
      cent. Eight (36%) patients had lesions with a Breast Imaging Reporting and Data
      System (BI-RADS) classification of 4 or 5. The sensitivity of preoperative core
      needle biopsy (CNB) to identify PASH was 83 per cent. A review of the literature
      revealed that 90 per cent of patients with PASH had some malignant imaging
      characteristics and 95 per cent had a mass on mammography. The imaging
      characteristics of PASH exhibited marked variability. Excision of PASH after CNB
      may be considered for patients with symptoms, enlarging lesions, or lesions
      classified as BI-RADS 4 or 5. PASH diagnosed by CNB allows selected patients to
      avoid excision.

PMID- 19097541
TI  - Successful completion of neoadjuvant chemoradiation and surgical resection for
      esophageal cancer after perforation: a case for endoscopic stenting.
AB  - Iatrogenic esophageal perforation during endoscopy in the setting of malignancy
      is an uncommon but often devastating complication and presents a formidable
      challenge to the surgeon. We sought to determine the efficacy of a self-expanding
      plastic stent for esophageal perforation before neoadjuvant chemoradiation in a
      single patient. A 74-year-old woman with a T4N0 adenocarcinoma at the
      gastroesophageal junction was perforated during upper endoscopy. We elected to
      manage the perforation with a silicone-covered, self-expanding Polyflex stent.
      Subsequent studies revealed good positioning of the stent with exclusion of the
      perforation from the esophageal lumen. The patient subsequently underwent
      neoadjuvant chemoradiation therapy with cisplatin, 5-flourouracil, and external
      beam radiation (2640 Gy) followed by minimally invasive, hand-assisted
      transhiatal esophagogastrectomy. We describe the first case of endoscopic
      stenting for locally advanced, perforated esophageal cancer for the purposes of
      administering neoadjuvant chemoradiation as a bridge to definitive surgery. This
      patient was able to resume oral nutrition after stenting and during neoadjuvant
      therapy, experiencing no major complications from chemoradiation. Chemoradiation
      does not necessarily preclude the use of endoscopically placed covered plastic
      esophageal stents as a bridge to resection, even in the face of iatrogenic
      perforation.

PMID- 19097542
TI  - Recurrent retrograde jejunogastric intussusception.

PMID- 19097543
TI  - Chilaiditi's syndrome with cecal volvulus and perforation.

PMID- 19097544
TI  - Treatment of in-transit metastases from Merkel cell carcinoma with isolated
      hyperthermic limb infusion.

PMID- 19097545
TI  - Tuberculous peritonitis: definitive diagnosis by laparoscopic peritoneal biopsy.

PMID- 19097546
TI  - An unusual cause of life-threatening rectal bleeding.

PMID- 19097547
TI  - An unusual case of insulinoma.

PMID- 19097548
TI  - Locally recurrent angiosarcoma after excision in a patient treated with breast
      conserving therapy.

PMID- 19097549
TI  - Angiosarcoma of the scalp.

PMID- 19097550
TI  - Parent-child reading interactions among English and English as a second language
      speakers in an underserved pediatric clinic in Hawai'i.
AB  - PURPOSE: The purpose of this study was to compare reading patterns between
      English-speaking and English as a Second Language (ESL) families in a health care
      setting in Hawai'i. METHODS: A cross-sectional study was performed at an
      underserved pediatric primary care clinic in Hawai'i. Caregivers of patients
      between the ages of 6 months to 5 years were asked questions regarding
      demographics and parent-child reading interactions. Respondents were categorized
      into English-speaking or ESL groups based on primary language spoken at home.
      Pearson chi2 tests and Fisher exact tests were performed to compare demographic
      differences, reading frequency, and reading attitudes between groups. RESULTS:
      One-hundred three respondents completed the survey Fifty percent were ESL. All
      ESL respondents were of Asian-Pacific Islander (API) or mixed Asian ethnicity.
      All Caucasians in the study (n = 9) were in the English-speaking group. Between
      the English-speaking (n = 52) and ESL (n = 51) groups, there were no significant
      statistical differences in age or gender of the child, reading attitudes, or
      parent's educational status. Parents in the ESL group read to their children
      significantly fewer days per week than their English-speaking counterparts, had
      significantly fewer books in the home, and lived significantly fewer years in the
      United States. CONCLUSION: The findings suggest that API immigrant families share
      similar attitudes about reading as English-speaking families in Hawai'i but have
      significantly fewer books in their household and read significantly less
      frequently Physicians working with API populations should be aware that immigrant
      children may have fewer reading interactions and should counsel parents on the
      importance of reading daily.

PMID- 19097551
TI  - Prognostic factors and utility of scoring systems in patients with hematological
      malignancies admitted to the intensive care unit and required a mechanical
      ventilator.
AB  - RATIONALE: Mortality of patients with hematological malignancy requiring
      mechanical ventilation is high. Neither early prognostic indicators nor scoring
      systems that discriminate survivors from non-survivors to aid in end-of-life
      decision making have been identified. OBJECTIVE: To assess the outcomes,
      prognostic factors, and scoring systems of acute respiratory failure requiring
      endotracheal intubation in the intensive care unit (ICU) in patients with
      hematological malignancies. METHODS: Retrospective cohort study in the medical
      ICU of a tertiary hospital. Thirty-three critically ill patients with
      hematological malignancies requiring mechanical ventilation were analyzed for
      demographic data, ICU survival, type of malignancy state of disease, reasons for
      hospitalization and ICU admission, peripheral blood parameters and scoring
      systems (APACHE II, SOFA, SAPS II, and MODS) during ICU stay All recorded
      variables were evaluated for prognostic relevance by univariate and multivariate
      analyses. MEASUREMENTS AND RESULTS: Overall ICU mortality was 74%. Univariate
      analysis revealed statistically significant differences in red blood cell count,
      hemoglobin, mean arterial pressure, coagulation studies, as well as the presence
      of oliguria, multi-organ failure, vasopressor requirement, pneumonia, blood
      product requirement. APACHE II, SOFA, and SAPS II scales also revealed similar
      statistical significance in outcome. However, multivariate analysis did not
      reveal any independent prognostic factors statistically. Among these, hemoglobin
      level appears to be the strongest trend (p = 0.0577) for survival. CONCLUSIONS:
      Mortality of patients with hematological malignancies requiring mechanical
      ventilation remains high. No single independent risk factor for ICU mortality was
      identified with multivariate logistic regression analysis. Prognostic scoring
      systems do not yield adequately reliable information to be used exclusively for
      end-of-life decision making in individual patients.

PMID- 19097552
TI  - Factor XIII deficiency (fibrin stabilizing factor).
AB  - Factor XIII deficiency (fibrin stabilizing Factor or FSF) is a rare coagulation
      defect. The only patient believed to have this disorder in Hawai'i is presented
      in this report.

PMID- 19097553
TI  - Establishing an Institute for Childhood and Adolescent Obesity Research and
      Education.

PMID- 19097554
TI  - Korean cancer incidence in Hawai'i: a population in transition.

PMID- 19097555
TI  - Managed care considerations: vulnerable populations and prevention strategies for
      respiratory syncytial virus disease.

PMID- 19097556
TI  - RSV disease in the pediatric population: epidemiology, seasonal variability, and
      long-term outcomes.
AB  - Infants younger than 1 year, and especially premature infants, are susceptible to
      severe RSV disease, which accounts for up to 126,000 hospitalizations each year.
      In the United States, the RSV season generally extends from November though
      March, but varies considerably both temporally and geographically. Studies, such
      as the one we have conducted in Colorado, indicate that the RSV season can even
      vary among local communities. In addition to seasonal variability, other
      independent risk factors also have to be taken into consideration when
      considering RSV immunoprophylaxis. Among these are a GA of less than 33 weeks,
      infants with CLD or CHD or who are immunosuppressed, male sex, household
      crowding, and daycare attendance. Exposure to indoor tobacco smoke and
      abbreviated breast feeding (less than 2 months) also may be pertinent risk
      factors. The Colorado studies show that high altitude also increases the risk of
      RSV hospitalization. Although hospitalization is a major outcome of severe RSV
      infections in infants, the development of wheezing and physician-diagnosed asthma
      later in life may be a long-term outcome that should be considered.

PMID- 19097557
TI  - In the trenches: a pediatrician's perspective on prevention and treatment
      strategies for RSV disease.
AB  - Pharmacologic options in the treatment of RSV infection have no or minimal
      effectiveness. Therefore, for infants at high risk of RSV infection, proper hand
      hygiene, limiting exposure to infection, and immunoprophylaxis with palivizumab
      is paramount. The first injection of palivizumab must be given prior to the start
      of the local RSV season and subsequent injections should be administered every 30
      days to provide protective levels until the end of the RSV season. Pediatricians
      should anticipate the start of the RSV season and attend to reimbursement issues
      and obtain all necessary approvals well in advance of the time when the first
      injections will be given. Compliance is the key to providing protection for high
      risk infants. Compliance has a positive association with decreasing RSV
      hospitalization rates; however, it is difficult for pediatricians to achieve
      optimal compliance on their own. A collaborative effort involving the hospital
      and NICU, pediatrician, parent, home care provider, and insurer is necessary to
      achieve optimal compliance.

PMID- 19097558
TI  - RSV infection in the adult population.
AB  - RSV is a significant and unrecognized cause of seasonal RTIs in adults,
      accounting for as much as 25 percent of excess wintertime mortality usually
      attributed to influenza. Nearly 80 percent of RSV-associated underlying
      respiratory and circulatory deaths occur among the elderly, and RSV is estimated
      to account for about 180,000 hospital admissions each year at a cost exceeding $1
      billion. RSV also is recognized as an important cause of viral pneumonia in
      adults. Preventive measures, such as hand washing, are paramount, especially in
      hospitals and nursing homes where many immunocompromised patients reside. When
      RSV is circulating, it is advisable to minimize contact between high-risk
      patients and children.

PMID- 19097559
TI  - Health plan medical director: considerations for prevention and management of RSV
      disease.
AB  - At Humana, our intent is to provide RSV immunoprophylaxis to all our members who
      need it quickly and efficiently. Humana's CareHub is a collaborative guidance
      model that fully engages our members and their health care providers, and allows
      us to leverage technology to develop a comprehensive clinical profile for each
      member and to share information. This clinical profile provides many ways in
      which we can identify those children who are at high risk of severe RSV
      infection, allowing us to implement RSV treatment and management quickly and
      effectively before the RSV season begins.

PMID- 19097560
TI  - Breastfeeding and human development.

PMID- 19097561
TI  - Traumatic events and depressive symptoms among youth in Southwest Nigeria: a
      qualitative analysis.
AB  - Traumatic experiences have dire consequences for the mental health of young
      persons. Despite high rates of traumatic experiences in some African cities,
      there are no reports for Nigerian youth. OBJECTIVE: To investigate the pattern of
      traumatic events and their association with depressive symptoms among youth in
      Southwest Nigeria. METHODS: This is a descriptive cross-sectional study of
      randomly selected youth in urban and rural schools in Southwest Nigeria. They
      completed self-reports on traumatic events and depressive symptoms using the
      Street Children's Project Questionnaire and the Youth DISC Predictive Scale
      (DPS). RESULTS: Of the 1,768 responses (88.4% response rate) entered into the
      analysis, 34% reported experiencing a traumatic situation. Following
      interpretative phenomenological analysis, 13 themes emerged. Frequently occurring
      traumatic events were 'road traffic accidents' (33.0%), 'sickness' (17.1%), 'lost
      or trapped' (11.2%) and 'armed robbery attack' (9.7%). A bad dream was described
      by 3.7%. Traumatic experiences were commoner in males (36.2%) than in females
      (31.6%) (x2 = 4.2; p = .041). Experiencing a traumatic event was associated with
      depressive symptoms (X2 = 37.98; p < .001), especially when the event directly
      affected the youth as in sexual assault or physical abuse. CONCLUSIONS: One-third
      of youth in Southwest Nigeria have described an experienced traumatic event. Road
      traffic accidents, armed robbery attacks, and communal disturbances depict the
      prevailing social environment, whereas 'bad dreams' revealed the influence of
      cultural beliefs. Policy makers must be aware of the social issues making an
      impact on the health of youth. Multi-agency interventions to improve the social
      environment and provide mental health services for traumatized young people are
      essential.

PMID- 19097562
TI  - Has early initiation of sexual activity in adolescence had an impact on teenage
      childbearing in Trinidad and Tobago?
AB  - Published data indicate that young people are initiating sexual activity at an
      early age and many do not practice contraceptive methods, which should impact on
      adolescent fertility and births. OBJECTIVES: The aim of this study was to
      determine the impact of sexual activity at an early age on adolescent
      childbearing in Trinidad and Tobago. STUDY GROUP: Adolescents age 15-19 years.
      METHODS: All maternity records from public health care institutions (primary and
      tertiary) under the Ministry of Health caring for women in pregnancy were
      reviewed. Maternal age at the time of birth in addition to several other
      variables were recorded and several indices were constructed to determine trends
      in adolescent fertility and births. RESULTS: There was a steady decline in
      adolescent births especially from 1981 to 1990. reduced by approximately 50%.
      Adolescent fertility rates and the number of adolescents attending prenatal
      primary care clinics during the same period showed similar trends. CONCLUSIONS:
      Analysis of adolescent fertility rate would suggest that initiating sexual
      activity at an early age together with low utilization of contraceptive practices
      should lead to its increases over time. However we found that there was both a
      decline in fertility rates as well as adolescent births.

PMID- 19097563
TI  - Parental bonding and depression: personality as a mediating factor.
AB  - According to Bowlby's theory of attachment, the role of early experience and
      parenting is of crucial importance to child development and mental health. In
      addition, several research findings suggest that parental bonding and different
      types of attachment play a crucial role in personality development. The present
      study examines the association between parental bonding experiences (lack of
      parental care, overprotection or both) and depression during adulthood. The
      objective of the present study was to evaluate different personality dimensions
      as possible mediators of the relation between perceptions of parental bonding and
      depressive symptoms in adult life. METHODS: 181 participants (15- 49-years-old)
      completed the Parental Bonding Instrument (PBI), the Beck Depression Inventory
      (BDI) and the 16 Personality Factor Questionnaire (16PF). RESULTS: The results
      show that lack of parental care and overprotection is linked with depressive
      symptoms and a number of personality characteristics, such as low self-esteem,
      introversion, distress and emotional instability. In contrast, high care and low
      protection (optimal bonding) is linked with increased self-confidence, less
      distress and less depressive symptoms. CONCLUSIONS: The results presented here
      are in line with Bowlby's theory of attachment and show that parental bonding is
      linked with problematic personality development and psychopathology. The present
      study provided evidence that personality factors may mediate the observed
      relationship between parental rearing style and depression. The potential causal
      mechanisms warrant longitudinal evaluation.

PMID- 19097564
TI  - Family structure and risk behaviors in Greek adolescents: a short report.
AB  - Changes in family structure may have negative outcomes on the well-being of
      adolescents. A sample of 500 students completed a self-report questionnaire on
      their family structure, housing status, and risk behaviors, such as smoking,
      drinking, substance abuse, and violence during their adolescence. We present the
      results of a study regarding the burden of adolescent risk behaviors in relation
      to family structure in Greece. 16.6% reported that their parents were divorced
      and they lived in a single-parent family. 42% of the respondents reported smoking
      during their adolescence. The prevalence rate of regular drinking was slightly
      higher for adolescents who had experienced family breakup compared to those who
      lived in an intact family, 24.4% and 22.7% respectively. 63.4% of the
      participants who had experienced family violence were extremely violent in
      school. There is a need for effective prevention programs in Greece in order to
      reduce the burden of adolescent health-risk behaviors and the associated cost for
      their parents and our society.

PMID- 19097565
TI  - The impact of sex education on HIV knowledge and condom use among adolescent
      females in the Dominican Republic.
AB  - The Dominican Republic has witnessed a significant increase of HIV/AIDS in recent
      years, particularly among young women. Prior research suggested that sex
      education could be an effective tool in combating risky sexual behaviors in
      adolescents; yet, most of this research has been conducted with Caucasian study
      populations, resulting in limited generalizability to Latino populations. The
      present study sought to address this gap by examining the effects of sex
      education on HIV/AIDS knowledge and condom use among young women in the Dominican
      Republic. METHODS: Data were analyzed from 1,608 female adolescent and young
      adult respondents to the ENJOVEN survey. Logistic regression models were used to
      investigate the relation between exposure to sex education and HIV/AIDS
      knowledge, current and consistent condom use. RESULTS: Respondents who reported
      receiving sex education were 1.72 times more likely to have high HIV/AIDS
      knowledge than respondents who reported not receiving sex education (CI: 1.36
      2.18, p = .000). Respondents who reported receiving sex education were 2.52 times
      more likely to report currently using condoms than respondents who reported not
      receiving sex education (CI: 1.65-3.85, p = .000). CONCLUSION: The results
      provide additional evidence that sex education programs are effective at
      increasing HIV/AIDS knowledge and condom use in young Dominican women.

PMID- 19097566
TI  - Prevalence of smoking among Greek students: a short report.
AB  - The aim of this study was to determine the prevalence of smoking and its
      associated factors among Greek students. Out of 1200 participants, 47% reported
      smoking, even one or two puffs (50.8% females and 43.8% males). The mean age of
      initiation of smoking was 17.1 +/- 1.9 years. Living in a single-parent family
      was not a significant risk factor for smoking. However, having more than one
      family member who smokes influences the smoking behavior in young people.

PMID- 19097567
TI  - Marked smoking-associated increase of cardiovascular risk in childhood type 1
      diabetes.
AB  - Type 1 diabetes is a generally accepted atherogenic risk factor, and diabetic
      patients who smoke markedly accelerate the atherosclerotic process. The main
      intentions of our investigation were to ascertain differences between juvenile
      active/passive smokers and non-smokers with type 1 diabetes regarding the number
      and spectrum of cardiovascular risk factors and their associations with smoking.
      Ninety-two patients were enrolled comprising 19 active/passive smokers (median
      age 15.9 years) and 73 non-smokers (median age 12.3 years). To determine age
      dependent influences we compared age- and gender-matched groups of 12 smokers
      with 12 non-smokers. Smokers had significantly higher HbA1c, fructosamine, total
      cholesterol, LDL cholesterol, apolipoprotein B, serum P-selectin, and lower serum
      L-selectin than non-smokers. However, L-selectin levels were not different
      between the age-matched smoker and non-smoker groups. A significant positive
      relation (Spearman rank correlation) was found between smoking and age, HbAlc,
      fructosamine, total cholesterol, apolipoprotein B, and P-selectin; a negative
      relationship between smoking and L-selectin. We conclude that smoking in children
      and adolescents with type 1 diabetes increases the cardiovascular risk through
      the deterioration of glucose metabolism, lipid profile, and endothelial function.
      Therefore, smoking diabetic juveniles may increase their number of cardiovascular
      risk factors from 1, diabetes, by another four factors, i.e. smoking,
      hyperglycemia, dyslipidemia, and endothelial perturbation.

PMID- 19097568
TI  - Anthropometric characteristics of Indian school children living in Bahrain.
AB  - A cross-sectional study was carried out among Indian school children residing in
      Bahrain to assess their physical growth. The total sample of 1,437 Indian school
      children (718 males and 719 females) aged 6-18 years were selected by a
      systematic random sampling technique. Anthropometric measurements included
      measurement of height, weight, mid-arm circumference, biceps, triceps,
      subscapular, and suprailiac skinfold thickness. RESULTS: Median height of the
      boys was between the 10th and 25th percentile of the National Centre for Health
      Statistics (NCHS) standard growth charts. In girls, the height varied between the
      5th and 25th percentile, dipping to nearly the 5th percentile at 14 years. Median
      weight of the boys fluctuated between the 25th and the 50th percentile of the
      standard data and in girls, weight fluctuated between the 25th and 50th
      percentile. Girls had a higher mean body mass index (BMI) and body fat compared
      with the males at all age groups. The median BMI for both groups was between the
      50th and 75th percentile of the standard charts. The median triceps skinfold in
      males was above the 85th percentile at 17 years, whereas in females, skinfold
      thickness was steady between the 50th and 85th percentiles of the growth charts.
      CONCLUSION: Compared with their Bahraini counterparts, two distinct growth
      patterns were evident. When compared with early data, the Indian children were
      taller and heavier than their Bahraini counterparts. However, comparison with
      later data showed a reversal, whereby the Bahraini children were taller and
      heavier with a corresponding higher BMI.

PMID- 19097569
TI  - Using population attributable risk to help target preventive interventions for
      adolescent depression.
AB  - Prevention of adolescent depression has become a public health priority in the
      United States (US) and in other developed economies. Population attributable risk
      (PAR) can provide an estimate of the incidence reduction that would occur if a
      particular factor were removed. OBJECTIVE: To determine PAR of vulnerability
      factors for new-onset depressive episodes in United States (US) adolescents.
      STUDY GROUP: National Longitudinal Study of Adolescent Health. The sample was
      comprised of nationally representative adolescents in grades 7-12, with mean age
      of 15.7 years. METHODS: We determined PAR for identified vulnerability factors
      for US adolescents measured at baseline predicting a depressive episode at one
      year follow-up. The baseline factors included socio-demographics and physical
      health factors; interpersonal relations; community and school factors and
      cognition/affect regulation. RESULTS: Factors with significant PAR were
      identified from each major domain of adolescent life. With the exception of age,
      sexual activity had the highest PAR. Interpersonal relations, particularly those
      involving family members rather than peers, represented the most important group
      of contributing factors. Similarly, low levels of constructive community
      involvement (e.g. religious activity) and higher levels of delinquent activity
      had significant PAR. Current depressed mood had relatively high PAR whereas
      negative self-cognitions had relatively low PAR. CONCLUSIONS: Poor affect
      regulation, existent depressed mood, and accompanying negative cognitions are
      important potential intervention targets. Our findings also suggest expanding the
      focus of preventive interventions to encompass all interpersonal and community
      domains of the adolescent experience.

PMID- 19097570
TI  - Medical students: abuse of psychoactive substances and sexuality aspects.
AB  - University students aged 17 to 24 years of age are prone to many risk factors.
      OBJECTIVES: Identify risk factors related to exploring sexuality and
      characteristics of consumption of psychoactive substances in students attending
      medical school. METHODS: 465 Medical students from Santa Casa of Sao Paulo
      Faculty of Medical Sciences (FCMSCSP) were prospectively and transversely
      evaluated during 2005. An anonymous, semi-structured, self-filling questionnaire
      was used. The average age of the students was 21.5 years, 43% females. 76.2%
      preferred alcohol, and 11.1% tobacco consumption; chloroethane (lanca-perfume)
      consumption occurred in 22.6% and 15.3% consumption of other types of illicit
      drugs, with marijuana as the most used one (94%). 70.3%, of the parents drink
      alcohol and 30.5% smoke tobacco. As for the students' sexuality, 85.3% have
      already had sexual intercourses, starting at average age of 17. 88.8% used condom
      during the first sexual intercourse, however, 35.6% did not use it regularly;
      5.4% had already had some type of DST. 79.8% of the females preferred having used
      contraceptive methods; however, 28.1% had a suspicion of pregnancy, which was
      confirmed in 7.9% of the cases. 9.9% of the students had ideas of abortion, 12.5%
      have effectively attempted it. 85% found medical school stressing and to relieve
      tension, 33.8% practiced sports; 6.9% preferred either licit or illicit drug
      consumption, and 5% used tranquilizers. The results showed risk behaviors: unsafe
      sex and the use of licit and illicit drugs indicated the need to establish
      guidance programs on reproductive health, improving self-esteem, and prevention
      during medical education.

PMID- 19097571
TI  - Perceptions of adolescents and their mothers on reproductive and sexual
      development in Matlab, Bangladesh.
AB  - Adolescence is the stepping stone for a child to reach adulthood. Although
      generally delimited by age, this stage is primarily a social and cultural
      classification based on markers of development, such as menarche (the first
      menstruation of girls) and spermarche (indicated by the first self-reported
      ejaculation of boys as proximity). OBJECTIVE: Aim of this study was to
      investigate the perceptions of adolescents and their mothers on markers of
      reproductive and sexual development. STUDY GROUP: The study was conducted among
      12 to 16-year-old adolescent girls and boys, in Matlab, Bangladesh. Their mothers
      were also interviewed. METHODS: Data were collected by means of a survey and
      through in-depth interviews. RESULTS: The study revealed that adolescent girls
      and boys are not adequately informed about menarche and spermarche, indicating a
      less than optimal mental wellbeing in reproductive life. No less than 64% of the
      adolescent girls reached menarche in fear. The lack of knowledge about the
      origins of menstruation seems to be an intergenerational problem as the mothers
      lacked adequate information as well. CONCLUSIONS: This paper argues that having
      an understanding of reproductive development is a prerequisite to being able to
      make contemporary and future informed choice(s). In Bangladesh, mental well-being
      in reproductive life is a dimension that is easily overshadowed by the physical
      aspects of reproductive health. Sexual education for adolescent girls and boys
      must be programmed urgently, to improve not only their own sexual and
      reproductive health status but also that of future generations.

PMID- 19097572
TI  - Medical supervision of young female athletes training in complex coordinational
      sports.
AB  - This article proposes simple medical criteria that can be used by trainers and
      others for effective medical supervision of young female athletes. METHODS: The
      cross-sectional, age-stratified study compared girls 10-17 years of age involved
      in intensive training in gymnastic floor exercises, trampoline, or badminton.
      Each sport and/or control group was represented by 40-45 girls. Data included
      medical history, morphometric variables and observation of biological
      development. RESULTS: Gymnasts started training earliest (approximately 5-years
      old) and trained most intensely (18-20 h/wk), followed by trampolinists and then
      badmintonists. Height, weight, body mass index, and % body fat were reduced in
      athletes, with gymnasts showing the greatest reduction. Athletes showed higher
      ratios of leg length to height and shoulder width/hip width, and smaller pelvic
      size compared to height. The average age of menarche of gymnasts was 13.8 (1.6
      year later than controls). Delays of biological development of more than 2 years
      were common in athletes, and some gymnasts showed more than a 4-year delay. These
      delays were related to morphometric indicators of hormonal imbalance and to low
      body fat. Gymnasts had more childhood diseases, with an infection index of 2.8
      compared to 1.1 for the control group, and had a higher level of chronic ENT
      problems. CONCLUSIONS: Trainers need to protect the health of athletes. During
      the course of training, anamneses, delayed menarche and other signs of delayed
      biological development must be monitored. Morphometric measures and indicators of
      biological development are proposed to provide simple criteria important in
      protecting the athletes' health.

PMID- 19097573
TI  - Behavioral and other characteristics of relevance for health in adolescents with
      self-perceived sleeping problems.
AB  - AIM: To study the associations between self-perceived sleeping problems and wide
      areas of adolescent life. METHODS: All eligible adolescents 13-18 years old (3216
      pupils) in a medium-sized town in Sweden completed a validated in-depth
      questionnaire (Q90), with 165 questions. RESULTS: Nine hundred and thirty-two
      (29.3%) adolescents (36.3% among girls; 21.9% among boys) reported having poor
      sleep, combined with daytime tiredness in the vast majority. Significant
      independent associations in specific age and gender groups were found for
      'feeling depressed', breakfast habits, 'I do well in school' (inverse), physical
      training (inverse), no adult to talk to, having bullied someone, shop-lifting,
      physical fighting, not feeling healthy, abdominal pain, headache, tobacco use,
      and sexual experience. CONCLUSIONS: Many of these adolescents feel very poorly,
      as is evident from the magnitude of the problems. Poor sleepers form an easily
      recognized group, but it seems unlikely that therapy for sleeping problems alone
      would be successful in a large proportion of these adolescents.

PMID- 19097574
TI  - Characterizing health behaviors and infectious disease prevalence among Filipino
      street children.
AB  - PURPOSE: To describe health problems and social, environmental, and health
      behavior characteristics among street children in Manila, Philippines. METHODS: A
      cross-sectional survey and clinical tests that included chest radiographs blood,
      urine, and stool samples were completed with 179 street children, ages 8-17
      years, served by Childhope-Asia Philippines. RESULTS: The most frequently
      occurring health problem was coughing, followed by fever, dyspnea, diarrhea, and
      then blood in the stools. Males compared with females were more likely to be
      kicked, punched, or slapped by an adult. Among males, 65% are current smokers and
      52% have consumed alcohol. Among females, 37% are current smokers and 67% have
      consumed alcohol. The percentage of children with low hemoglobin was 91% for
      males and 16% for females. The percentage of children with low hematocrit was 69%
      for males and 22% for females. Of all children tested, 7.9% had hepatitis B,
      12.3% had pneumonia, and 25.5% had ascariasis. CONCLUSIONS: Filipino street
      children have a high level of infectious disease, with females experiencing
      higher levels of coughing, dyspnea, and fever whereas males had higher levels of
      diarrhea. Males are more likely to be physically abused and to smoke tobacco
      whereas females are more likely to drink alcohol. Both males and females
      experienced depression and anxiety and many children were sexually active.
      Diseases common among the population are pneumonia, anemia, hepatitis B and
      ascariasis, primarily due to their lack of adequate nutrition, close living
      proximity, and unsanitary living conditions.

PMID- 19097575
TI  - Parental attitude toward unaccompanied clinic visits of adolescents.
AB  - To describe parental attitudes regarding the age and the type of medical problems
      that are appropriate for adolescent unaccompanied visits to the clinic at an age
      younger than 18 years. METHODS: A structured interview was conducted with parents
      who visited two community clinics with their children. The questionnaire
      included: 1) At what age would you allow your child to visit the clinic alone? 2)
      What medical conditions are acceptable for unaccompanied visit at the age you
      stated (if lower than 18 years)? and 3) What medical conditions are not
      acceptable for unaccompanied visit at the age you stated (if lower than 18
      years)? RESULTS: Two hundred and fifty three parents were interviewed. There was
      an agreement between parents from the two clinics regarding the mean age
      appropriate for an unaccompanied visit (mean 14.1 +/- 2.56 years for clinic A and
      13.8 +/- 2.66 years for clinic B). Medical conditions most acceptable for
      unaccompanied visits were common cold (clinic A = 77.4%, clinic B = 70.5%), sore
      throat (A = 64.5%, B = 84.3%) and fever (A = 34.7%, B = 19.4%). Medical
      conditions most unacceptable for unaccompanied visit were: injury (clinic A =
      68.5%, clinic B = 53.5%), fever (A = 37.1%, B = 42.6%) and severe illness (A =
      19.4%, B=23.3%). CONCLUSIONS: most parents were willing to allow their adolescent
      children unaccompanied visits to the physician at an age below that stipulated by
      law. As unaccompanied visits are widely practiced and accepted by the public, it
      might be necessary to amend the law.

PMID- 19097576
TI  - Trends in the number of children in Israel 1970-2006.
AB  - Information and data are important for planning in any society. The number of
      children and adolescents in a community determines the demand for schools, health
      care facilities and other services for children and their families. Health,
      safety, education, recreation and social development are areas, where society
      needs to plan and invest, but this must be done according to reasonable
      predictions in order to be effective. We have in this communication looked at the
      trends in the number of children in Israel and found that during 1970-2006 the
      child population in Israel increased by 100% with the most increase in the Muslim
      child population (190.8%). The percentage of children of the whole population
      decreased from 39% to 33% in the study period in spite of the increase in number
      of children over the period. Irrespective of the decrease it is still high
      compared to for example 26% in the United States, so the population in Israel is
      still a younger one and service planning must be geared toward this demographic
      trend.

PMID- 19097577
TI  - [The investigation of presence of genetically modified protein in processed
      foodstuffs by ELISA test].
AB  - The test based on immunoassay--TRAIT-RUR Toasted Soy Meal Kit was used for
      detection GMO-soy protein in the processed (heat treated) foodstuffs: bread,
      macaroni, sausages, ready-to-serve products and soya products (tofu, steaks). The
      threshold level is about 0,6% protein. The positive results were obtained for 27
      from 106 investigated products. Only 5 foodstuffs were declared as containing GMO
      soy in composition. The presence of genetically modified ingredients in
      foodstuffs must be controlled. The proper information should be labelled for the
      consumer.

PMID- 19097578
TI  - The contents of nitrates (III) and (V), added polyphosphates and total levels of
      phosphorus, calcium, magnesium, iron and zinc in some cured meat products.
AB  - The aim of the study was to determine the contents of nitrates (III) and (V), the
      originally added and total phosphorus as well as levels of calcium, magnesium,
      iron and zinc in selected Polish cured poultry and pork products. Also, the
      degree to which such products satisfy recommended dietary requirements for the
      above minerals in adults was assessed.

PMID- 19097579
TI  - [Levels of polychlorinated biphenyls in human milk in dependent on selected
      factors].
AB  - The contents of polychlorinated biphenyls in human milk were determined. The PCB
      levels in human milk were determined in relation to factors such as: age and
      weight of women, birthweight of the baby, smoking, period of breast-feeding (3-5
      days, 2-4 weeks, 6-8 month) and seasons of the year. It was found that level of
      PCB in human milk have been decreasing during lactation. PCB levels in human milk
      decreases with increasing weight of women. The level of PCB in human milk
      increases together with age of women. The higher PCB levels were determined in
      human milk from women smoking cigarettes.

PMID- 19097580
TI  - [Incidence of the virulence markers iam in Campylobacter jejuni and Campylobacter
      coli strains isolated from poultry carcases].
AB  - Previously found DNA sequence (iam), correlated with the invasiveness of
      Campylobacter strains, became a starting point for present investigation. Main
      goal of this study was to isolate number of Campylobacter strains from chicken
      carcasses, to determine their taxonomic position and to establish the presence of
      iam sequence in their genoms. It was found, that invasion associated marker is
      present in all Campylobacter coli strains and in majority but not all
      Campylobacter jejuni. This may confirm the idea that the marker is not only
      responsible for diarrhea in humans but also may be important in the colonization
      of chicken guts.

PMID- 19097581
TI  - [Composition of chlorobiphenyl congeners in the Chlorofen formulation].
AB  - Qualitative and quantitative composition of di- to octa-CBs have been determined
      in the Polish PCB mixture Chlorofen after HRGC-LRMS and 2D-HPLC and HRGC-HRMS
      separation, identification and quantification. 103 peaks representing up to 121
      congeners from di-to octa-CB were quantified. Of the highly toxic planar PCBs
      only PCB IUPAC no. 77 was found at 10 microg/g concentration, while nos. 81, 126
      and 169 were absent. Of the di- to octa-CBs a dominating congeners quantified in
      Chlorofen were nos.: 196/201 (19.7%), 194 (16.6%), 180 (12%),198 (9.5%), U7CB
      (8.6%) and 153 (5.3%).

PMID- 19097582
TI  - [Protein intake in selected youth groups of different physical activity and
      requirements for athletes].
AB  - The aim of the study was to investigate protein intake in groups of different
      physical activity. The research was undertaken over a group of young people of
      different physical activity (age group 15-18 years) including ballet dancers,
      karate fighters, cross runners as well as adolescents of average physical
      activity (female and male). The investigation was performed in two series. The
      first--before intense exercise training and the second--after intense exercise
      training. In control group there was only one series. Urea was estimated by using
      urease which converts urea into ammonia, CO2 and glutamic dehydrogenase reaction
      via measurements of ammonia derived from urea. The amounts of urea were applied
      for counting quantity of consumed proteins. In the physically active groups the
      protein intake was too low in comparison to required.

PMID- 19097583
TI  - [The comparison of fat, trans isomers and cholesterol intake in the diet of
      Warsaw inhabitants in relation to Polish food ration].
AB  - The aim of the study was to establish the intake level of fat, linolenic and
      linoleic acids, trans fatty acids and cholesterol in an average diet of Warsaw
      adult inhabitants in comparison with the Polish diet. The intake of nutrients in
      an average diet of Warsaw adult inhabitants was estimated based on research data
      gathered using three-day dietary records in 2001/2002 as well as the research
      results of household budgets, elaborated by the Central Statistical Office in
      1998 and 2001. Excessive consumption of fats in the diet resulted from high
      consumption of fried products, adding fat to dishes and the consumption of high
      fat milk and meat products. Moreover, a low consumption of linolenic acid and a
      high participation of linoleic acid was proved in the diet. Excessive consumption
      of linoleic acid was the result of high consumption of oil fried products and
      using margarines for spreading. The intake of trans fatty acids in Warsaw diet
      was higher than recommended as a result of high great consumption of margarines
      and hydrogenated fat, while the intake of trans fatty acids in Polish diet did
      not exceed maximum recommended amount. Excessive level of cholesterol in the diet
      was the result of high consumption of meat, meat products and eggs. The results
      indicate that it is necessary to decrease the intake of fat in the diet,
      especially hydrogenated fat, and replace them with oil rich in alpha-linolenic
      acid, e.g. rape oil as well as consume more sea fish and fish products. It is
      recommended that high fat meat and meat products should be replaced with the lean
      ones and that low-fat milk and milk products should be consumed.

PMID- 19097584
TI  - [Giving out extra meals to children at school in the District of Podlasie in year
      2003].
AB  - The aim of this article was to evaluate the access of school children to
      different forms of school lunch programmes in a range of schools in the District
      of Podlasie. Substantial materials for this study were provided for by MZ 53
      reports for the year 2003, which mainly concerned problems associated with
      hygiene of primary and secondary school children, as well as supplementary
      reports compiled by Regional Disease Control Centres in the District of Podlasie.
      In the area of Podlasie school meals were served as full and one-dish lunches.
      21.95% of all the schools served full lunches, 7.66% schools served one-dish
      lunches, with secondary and primary schools constituting the highest percentage.
      20.15% of the pupils took advantage of full lunches, 4.36% of one-dish lunches.
      264 schools put forward a motion of serving drinks, which constitutes 36.01%. The
      above mentioned drinks were mostly served in the country branches of primary
      schools (67.56%) and primary schools (43.6%), rarely in secondary schools
      (10.71%). In the schools of higher academic standard pupils were offered no
      drinks. Milk drinks were available all through the school year in 1.36% of
      schools (0.47% pupils took advantage) and 0.27% of schools in the winter season
      (0.07% pupils took advantage). 26.72% of all the institutions suggested
      organizing in-company breakfasts in schools, and these were solely primary and
      secondary schools. School buffets were in operation in 32.49% of schools and
      5.49% of schools had sweets and drinks machines vending pastry, fizzy and still
      drinks.

PMID- 19097585
TI  - [Questionnaire studies on the vital situation and nutritional habits of
      students].
AB  - Results of questionnaire studies carried out in 2001/2002 among 230 students of
      University of Agriculture in Szczecin were presented. It served for assessing
      their material and living situation during studying at the University. Women and
      people originating from cities dominated in studied group of respondents.
      Probably, there is a decreasing tendency referring to attending the University by
      country people. Residence during studying depended on the year of education and
      origin of respondents. Last-year students and country people were more often
      placed in hostel. Material help in a form of social scholarship was more often
      assigned to country youth, and scientific grants were more frequently given to
      fifth-year students. No finance help of student's families made they undertook a
      part-time job that was made more often by final-year students. Significant
      differences referring to consumption customs often depended on sex. Students
      themselves most often prepared meals, including dinners. Only small per cent
      (12%) of students went to canteens, milk bars or other restaurants. Almost one
      third of respondents fed irregularly. One-dish dinners consisting most often of
      purchased or earlier prepared semi-products dominated. Majority of students
      declared feeding meat, poultry, and sweets at least once a week, as well as fish-
      at least once a month. Every second person declared everyday consumption of fruit
      and vegetables, milk and its products as well as several cups of coffee daily; it
      referred more often to women. Most of respondents occasionally consumed sprinkle,
      low-alcoholic beverages and snacks in a form of chips and nuts, but they were
      more often men.

PMID- 19097586
TI  - [The level of mother's education as the factor which differentiates healthy
      behaviour and physical development of young people].
AB  - The aim of the study was to estimate the differentiation of the physical
      development and chosen health behaviour patterns of secondary-school students
      depending on the level of mother's education. The greatest height and most
      slender body build as well as more rational eating habits and more favourable
      health behaviour patterns have been found among students whose mothers have
      higher education.

PMID- 19097587
TI  - [Smoking among school adolescents and the social environment].
AB  - The aim of the study was: (1) to assess the prevalence and intensity of tobacco
      smoking among 11 to 15-year old Polish adolescents in 2002; (2) to test the
      relationships between peer, parental and adolescents smoking; (3) acceptance of
      smoking among parents and friends; (4) smoking in the presence of parents and
      friends. The study was conducted in 2002 within the Health Behaviour in School
      aged Children: A WHO Collaborative Cross-national Study. The international
      standard questionnaire was used. A sample was selected as representative for
      general school population at three age groups: 11.7; 13.7; and 15.7. It was found
      that 44% of youth had already started to smoke tobacco, and 17% has smoked
      cigarettes with different frequency, 8% smoked everyday The higher percentage of
      regular smokers was found among the adolescents whose parents and peers smoked
      everyday. The rate of smokers who perceived their peers as smoking persons has
      considerably increased with age and depended on fact whether a tested person
      smoked himself/herself or not. Smoking among young people has taken place in
      various circumstances but most often in the company of other smoking people. They
      started to smoke alone very seldom. Frequency and intensity of smoking in various
      situations increase with age. One person in ten received the permission for
      smoking at home at the presence of their parents. Results of the survey may be
      used in school and local preventive interventions.

PMID- 19097588
TI  - Current proteomic analysis and post-translational modifications of biomarkers in
      human lung cancer materials.
AB  - Lung cancer is the leading cause of cancer deaths worldwide and is often
      diagnosed in the advanced or late stages. The discovery of candidate biomarkers
      in human lung cancer materials holds clinical potential as well as a significant
      challenge. Due to a large number of proteins in human materials that form the
      protein complexity and post-translational modifications (PTMs) of proteins,
      proteomic analysis of lung cancer biomarkers remains a difficult task. Many
      proteomic approaches have been used to investigate the biomarkers in human lung
      cancer materials. In this review, we summarize the current proteomic approaches
      employed for analysis of proteome profiles in human lung cancer materials and
      some PTMs causing different proteome profiles and expression levels of biomarkers
      in lung cancer. In addition, bioinformatic tools for PTMs are useful for
      prediction of glycosylation and phosphorylation sites in proteins, which can help
      us further understand the correlation of PTMs and tumor development. However, it
      is necessary that proteome analysis of lung cancer materials be incorporated with
      new strategies and technologies to improve the efficiency of the analysis and to
      investigate novel biomarkers that would be very useful for further diagnostic and
      therapeutic applications.

PMID- 19097589
TI  - Medical treatment of endometriosis.
AB  - Endometriosis is a common, benign and chronic gynecological disorder. It is also
      an estrogen-dependent disorder that can result in substantial morbidity,
      including pelvic pain, pro gressive dysmenorrhea, dyspareunia, infertility and
      repeat surgeries. Endometriosis is often treated surgically upon diag nosis but
      with a higher rate of recurrence, suggesting that a combination of surgical and
      medical management might provide better outcomes. The primary goal of medical
      treatment for endometriosis is to halt the growth and activity of endometriosis
      lesions. The most widely utilized medical treat ment for endometriosis involves
      use of gonadotropin-releasing hormone (GnRH) agonists and oral contraceptives.
      Conventional agents also include androgen derivates and progestins. Due to the
      chronic nature of this disease, long-term or Dr. Hong-Yuan Huang repeated courses
      of medication may be required to control its related symptoms. Increasing
      knowledge about the pathogenesis of endometriosis at the cellular and molecular
      levels may give us the opportunity to use new, specific agents for treatment,
      including aromatase inhibitors, progesterone antagonists, selective progesterone
      receptor modulators, GnRH antagonists, intrauterine releasing systems with
      progestin and new pharmaceutical agents affecting inflammation, angiogenesis, and
      matrix metalloproteinase activity. Many of these promising new agents may prevent
      or inhibit the development of endometriosis. Further clinical trials may
      determine if these new therapies are superior to current medical treatment
      strategies for endometriosis.

PMID- 19097590
TI  - The current status, evolution and future of facial reconstruction.
AB  - Facial reconstructive surgery aims to establish anatomic normality as closely as
      possible following disfigurement to optimize functional and esthetic outcomes and
      the potential for normal psychosocial patient reintegration. The purposes of this
      article are to outline the current status of facial reconstruction and reflect
      upon possibilities for its future development. Current reconstructive methods
      include the use of non-vascularized grafts, non-microsurgical vascularized flap
      transfers, microvascular free tissue transplantation, and their combinations.
      Whatever the method chosen, the principles of reconstruction for each facial
      region or esthetic subunit should b e respected. Most facial defects can be
      addressed satisfactorily with the described techniques. Reconstructions for total
      or subtotal facial defects, however, remain disappointing. Current reconstructive
      techniques and principles continue to become more refined, providing improved
      outcomes. In the future, composite tissue allotransplantation and tissue
      engineering of vascularized composite tissue constructs may also be applicable
      for facial reconstruction, in particular for total or subtotal facial defects
      that appear outside the limits of current reconstructive methods.

PMID- 19097591
TI  - Combined use of capsule endoscopy and double-balloon enteroscopy in patients with
      obscure gastrointestinal bleeding.
AB  - BACKGROUND: Most of the sources of bleeding in patients with obscure
      gastrointestinal bleeding are located in the small bowel. Capsule endoscopy (CE)
      and double-balloon enteroscopy (DBE) are innovative modalities to examine the
      small intestine. This study evaluated the combined use of CE and DBE in patients
      with obscure gastrointestinal bleeding. METHODS: From October 2005 to November
      2006, ten patients with obscure gastrointestinal bleeding who underwent CE
      followed by DBE were included in this study. The insertion route for DBE was
      determined according to the site of obscure gastrointestinal bleeding detected by
      CE in nine patients. The anterograde route was selected when the estimated
      location of the lesion was in the proximal two-thirds of the small bowel and the
      retrograde route was chosen when the estimated location was after the proximal
      two-thirds. In one patient without a definite lesion detected by CE, the route of
      insertion was determined according to clinical judgment. RESULTS: Eleven capsule
      endoscopies were performed in ten patients. Significant or suspicious small bowel
      lesions were discovered by CE in nine (90%; 9/10) patients, including
      angiodysplasia (n=3), active bleeding (n=3), a polypoid lesion (n=1), suspected
      enteritis (n=1) and gastric antral vascular ectasia with small bowel bleeding
      (n=1). Eleven DBE were performed in ten patients. Significant small bowel lesions
      were detected by DBE in eight patients (80%), including angiodysplasias (n=3),
      lymphangioectasias (n= 2), varices (n=1), polypoid lesion (n=1) and Dieulafoy's
      lesion (n=1). Endoscopic treatments were performed successfully in 7 patients,
      including argon plasma coagulation in four, heat probe coagulation in one,
      endoscopic mucosal resection in one and sclerotherapy in one. CONCLUSIONS: CE can
      provide useful information on the indications for DBE and the selection of the
      route of DBE. DBE can verify the findings of CE and provide therapeutic
      intervention. Combined use of CE and DBE is effective in the diagnosis and
      management of patients with obscure gastrointestinal bleeding.

PMID- 19097592
TI  - Sinonasal metastatic tumors in Taiwan.
AB  - BACKGROUND: To analyze the incidence of the metastatic tumors within sinonasal
      tract in Taiwan and review the data in the English literature. METHODS:
      Retrospective reviewed of patients from 1990 to 2005 with a histologically proven
      diagnosis of metastatic malignancies in the sinonasal tract. RESULTS: Among
      seventeen enrolled patients, 9 were men and 8 were women, with ages ranging from
      24 to 76 years old, with a mean of 50.8 years. In order of frequency, sinonasal
      metastatic tumors originated from the gastrointestinal tract (30%), liver (18%),
      kidney (18%), breast (18%), thyroid gland (12%) and lung (6%). CONCLUSION: The
      incidence and characteristics of metastatic neoplasms in Taiwanese patients are
      comparable to other countries in East Asia, except for Japan. However, our data
      are very different when compared with European and North American reports.
      Different incidences of malignant neoplasms in the primary site may explain the
      result of different incidences of sinonasal metastatic tumor.

PMID- 19097593
TI  - A transient blocking uterine perfusion procedure to decrease operative blood loss
      in laparoscopic myomectomy.
AB  - BACKGROUND: To evaluate the feasibility and effectiveness of reversible ligating
      clips to block uterine arteries and reduce operative blood loss during
      laparoscopic myomectomy (LM). METHODS: Twenty consecutive women with symptomatic
      uterine fibroids desiring to preserve the uteri underwent laparoscopic surgery
      with ligation of the uterine arteries with ligating clips, followed by myomectomy
      and removal of the clips. RESULT: Laparoscopic uterine artery ligation with
      reversible ligating clips was successfully performed in all patients. The median
      main fibroid diameter and fibroid weight were 7.3 cm (interquartile range [IQR]
      7.0-9.0) and 210 g (IQR 150-295 g), respectively. The median operating time was
      120 minutes (IQR 100-148 minutes) and blood loss was 100.0 mL (IQR 56.3-137.5
      mL). The median number of fibroids removed was 1 (IQR 1-4.3). The median post
      operative hospital stay was 3 days (IQR 2-3 days) and no patient developed
      complications. Menstrual bleeding problems and bulk-related symptoms were
      controlled in 90.0% and 100% of women, respectively after 6 months of follow-up.
      One woman conceived spontaneously 4 months after surgery and delivered a baby
      girl at 38 weeks gestation via cesarean section. CONCLUSIONS: Blocking uterine
      perfusion before LM is valuable and feasible for the management of women with
      symptomatic fibroids. The procedure controlled operative blood loss without
      affecting the uterine blood supply after surgery.

PMID- 19097594
TI  - Best diagnostic criterion in high-resolution ultrasonography for carpal tunnel
      syndrome.
AB  - BACKGROUND: High-resolution ultrasonography (HRUS) has been used to diagnose
      carpal tunnel syndrome (CTS) in recent years. However, the best diagnostic
      criterion and optimal cut-off value for HRUS remain controversial. METHODS: This
      study enrolled 37 patients with idiopathic CTS (61 CTS hands) and 20 healthy
      subjects (40 normal hands). The subjects underwent nerve conduction studies along
      with HRUS. Several ultrasonographic measurements with good reliability were
      compared, including the median nerve cross-sectional areas (CSA) at the pisiform
      and hook of hamate levels; the flattening ratios (FR) at the pisiform, hook of
      hamate, and distal radioulnar joint levels; retinacular bowing (RB); and the
      longitudinal compression sign (LCS). Receiver operating characteristic (ROC)
      curves were plotted for the optimal cut-off values as well as the sensitivity and
      specificity. RESULTS: There was a significant increase in the median nerve CSA at
      the pisiform and hook of hamate levels, RB, and LCS, but the FR was decreased at
      the hook of hamate level. The ROC curves demonstrated that the median nerve CSA
      at the pisiform level was most predictive of CTS; the optimal cut-off value was >
      or = 9.875 mm2, yielding 82% sensitivity and 87.5% specificity. CONCLUSIONS: CTS
      can be diagnosed by HRUS. The most useful diagnostic criterion is a median nerve
      CSA of > or = 9.875 mm2 at the pisiform level.

PMID- 19097595
TI  - Estradiol-to-testosterone ratio is associated with response to metformin
      treatment in women with clomiphene citrate-resistant polycystic ovary syndrome
      (PCOS).
AB  - BACKGROUND: To investigate intrinsic alterations in ovarian steroidogenesis in
      women with clomiphene citrate (CC)-resistant polycystic ovary syndrome (PCOS) who
      ovulated after metformin treatment. METHODS: Fifty-six women of reproductive age
      (18-40 years) diagnosed with CC-resistant PCOS received metformin for 12 weeks.
      If ovulation was successfully induced by CC after metformin treatment, the women
      were classified as responders. Circulating levels of follicle-stimulating hormone
      (FSH), luteinizing hormone (LH), estradiol (E2), testosterone (T), free
      testosterone (freeT), fasting insulin and sex hormone-binding globulin (SHBG)
      were determined at weeks 0, 4 and 12 of metformin treatment. RESULTS: Thirty
      seven women with CC-resistant PCOS finished the treatment course. There were no
      significant differences in circulating levels of FSH, E2, T, freeT and fasting
      insulin at weeks 0, 4, and 12 between responders and nonresponders. At week 4,
      responders showed significantly higher LH levels and higher LH/FSH ratios than
      non-responders (p < 0.005 and p < 0.05, respectively). After the 12-week
      treatment, responders demonstrated higher serum E2/T ratios and lower freeT
      levels than non-responders (p < 0.05 and p < 0.05, respectively). CONCLUSIONS:
      The results suggest that in women with CC-resistant PCOS, elevated E2/T is
      associated with a better response to metformin.

PMID- 19097596
TI  - Review of 20 years' clinical experience with retinoblastomas in southern Taiwan.
AB  - BACKGROUND: Retinoblastomas are the most common malignant intraocular tumor of
      childhood. We describe the survival outcomes and prognostic factors of patients
      with a retinoblastoma receiving primary treatment at our hospital over the last
      20 years. METHODS: A retrospective series study of 30 retinoblastoma cases
      treated from January 1, 1987 to August 31, 2006 was conducted from a review of
      medical records and histopathological sections. Variables, including age at
      onset, laterality, treatment modalities, treatment delay, and optic nerve
      invasion, were analyzed to elucidate the prognostic factors associated with
      cumulative survival. RESULTS: Most of the cases had an advanced retinoblastoma,
      and 23 patients received enucleation treatment. The average period of delay for
      treatment was 5.37 months after discovery of the disease. The overall cumulative
      survival rate was 83.08%. Patients with optic nerve invasion had a significantly
      lower survival rate (60.0%) than those without optic nerve involvement (94.75%).
      Treatment delay in excess of 6 months was correlated with tumor invasion of the
      optic nerve. CONCLUSIONS: Tumor invasion of the optic nerve is the most
      significant prognostic factor for surviving a retinoblastoma. Delayed treatment
      increases the risk of optic nerve invasion. Parental awareness of both the risk
      of this consequence and the significance of early treatment is vital to achieving
      improved survival rates.

PMID- 19097597
TI  - Vascular response of Raynaud's phenomenon to nifedipine or herbal medication
      (duhuo-tisheng tang with danggui-sini tang): a preliminary study.
AB  - BACKGROUND: Raynaud's phenomenon (RP) is a common manifestation in connective
      tissue diseases. Calcium channel antagonists are most effective and frequently
      used for treating RP. This study compared the efficacy, digital vascular
      response, and tolerability between nifedipine and a combination of 2 Chinese
      herbal medications (duhuo-tisheng tang and danggui-sini tang) for treating RP.
      METHODS: This open-label non-randomized clinical trial included 47 connective
      tissue disease patients with RP. The herbal group and the nifedipine group
      included 26 and 21 patients, respectively. The duration of therapy was 4 weeks.
      Baseline and posttreatment laser Doppler blood flow imaging of both hands were
      performed at room temperature and after cold challenge. Nailfold capillary
      microscopy was performed at the baseline and after 4 weeks of therapy. Serum
      levels of soluble intercellular adhesion molecule-1 (sICAM-1), prostaglandin E2
      (PGE2), nitrite (NO2), and nitrate (NO3), and plasma levels of endothelin-1 (ET
      1) were also measured. Self-reported symptoms, using a visual analog scale (VAS)
      and a physician global assessment (PGA), were recorded at the baseline and after
      treatment. RESULTS: After 4 weeks of treatment, VAS scores improved (p = 0.0035)
      and the physician's global assessment of RP severity decreased in the nifedipine
      group (p = 0.0078) but not in the herbal group. Episodes of RP attacks decreased
      in the nifedipine group after treatment (p = 0.008). The nifedipine group had
      increased laser Doppler flow (116.3 +/- 70.7 AU) compared to the baseline (72.4
      +/- 49.0 AU, p = 0.0008). Laser Doppler images improved at various time points
      after cold challenge in the nifedipine group after therapy. Laser Doppler flow in
      the herbal group did not significantly change with therapy. Capillary microscopy
      demonstrated no significant difference in enlargements, avascularity, or
      hemorrhagic spots between groups. Serum NO2 concentrations were higher in the
      nifedipine group than in the herbal group. Levels of sICAM-1, PGE2, NO3, and ET-1
      after therapy were similar to those at the baseline in both groups. CONCLUSIONS:
      The digital vascular response in RP improved with nifedipine but was unchanged
      with a combination of the Chinese medicines Duhuo-Tisheng Tang and Danggui-Sini
      Tang.

PMID- 19097598
TI  - Acoustic study in Mandarin-speaking children: developmental changes in vowel
      production.
AB  - BACKGROUND: Acoustic analysis had been well incorporated into clinical evaluation
      and management of children with speech disorders for many years. The aim of this
      study is to investigate developmental changes in vowel production in Mandarin
      speaking children using acoustic study analysis. METHODS: A total of 22 children
      from 5-12 years old were analyzed in this study. Each child read a list of speech
      materials consisting of 6 dissyllabic words in Mandarin phonemes and the speech
      samples were recorded. The digitized acoustic recordings were submitted for
      acoustic analysis. The acoustic parameters in this study include the first and
      second formant frequencies (F1 and F2) of /a/, /i/ and /u/ and the vowel space.
      We used the Wilcoxon rank sum test and Spearman's rho correlation test for
      statistical analysis. RESULTS: The F1 values of the vowel /i/ were significantly
      lower in boys than those in girls (p = 0.013) by Wilcoxon ranksum test. The F1
      value of the vowel /i/ was negatively correlated with children's age (rho = 
      0.601, p = 0.003) and their body height (rho = 0.478 p = 0.045). The F1 values of
      the other two vowels (/u/ and /a/), the F2 values of all three vowels and the
      vowel space had no association with age and gender. CONCLUSIONS: F1 acoustic
      parameters have developmental and gender changes in vowel production in Mandarin
      speaking children. The data in this study provide references for acoustic
      assessment of Mandarin-speaking children.

PMID- 19097600
TI  - Simultaneous development of renal cell carcinoma and multifocal urothelial
      carcinoma.
AB  - Simultaneous occurrence of multifocal urothelial carcinoma (UC) and ipsilateral
      renal cell carcinoma (RCC) is rare. We report a 67-year-old woman with
      multifocal, infiltrating urothelial carcinoma and unilateral renal cell
      carcinoma. She was referred to our department because of painless gross
      hematuria. Cystoscopy, computed tomography and retrograde pyelography studies
      revealed bladder, bilateral renal and ureter UC. She was treated with
      transurethral resection of the bladder tumor followed by bilateral
      nephroureterectomy. The pathological diagnosis was high-grade UC over the bladder
      and both renal pelves and ureters. A second tumor in the upper pole of the right
      kidney was reported as clear cell RCC. The patient was alive and still under
      careful surveillance at this writing.

PMID- 19097599
TI  - Imatinib-induced tumor lysis syndrome: report of a case and review of the
      literature.
AB  - Imatinib is a selective tyrosine kinase inhibitor which acts on breakpoint
      cluster region-Abelson fusion gene (BCR-ABL) positive leukemia including all
      phases of chronic myeloid leukemia and acute lymphoblastic leukemia. It may
      induce rapid apoptosis and subsequent tumor lysis syndrome. Only 3 cases of
      imatinib-induced tumor lysis syndrome have been reported. We herein described an
      additional patient with BCR-ABL (ela2) positive acute lymphoblastic leukemia who
      developed tumor lysis syndrome after 10-day treatment with imatinib. Experience
      in the current case suggests that preventive measures for tumor lysis syndrome,
      including allopurinol and hydration, should be taken for patients with high
      leukemia burden who receive imatinib therapy, and parameters of tumor lysis
      should be monitored in the early phase of therapy.

PMID- 19097601
TI  - Reader: Daschle's comments in November article objectionable.

PMID- 19097602
TI  - The lame duck budget: why should you care?

PMID- 19097603
TI  - Policing your commercial payments staying in (or getting in) the black.
AB  - Developing a program for auditing and recovering managed care underpayments is
      very important. Hospitals can use software applications designed to identify
      underpayments, focus on a manual auditing process, or implement a combination of
      the two.

PMID- 19097604
TI  - Diagnosis: missed opportunities for payment.
AB  - Southeastern New Mexico Hematology & Oncology of Roswell, N.M., lowered the rate
      of claims denials, expedited claims processing, improved accounts receivable
      (A/R), and decreased administrative costs by: Streamlining revenue cycle
      processes. Establishing a coding review board that monitors the coding changes
      made by all major insurers and Medicare. Working with a local foundation to help
      indigent patients purchase insurance and helping those that qualify for financial
      assistance receive aid. Outsourcing day-today billing functions.

PMID- 19097605
TI  - Community benefit how much is enough?
AB  - The IRS's Revenue Ruling 69-545, issued in 1969, remains the standard for
      determining whether the amount of community benefit a not-for-profit hospital
      delivers justifies its tax-exempt status. The revised IRS Form 990 will give
      hospitals an opportunity to demonstrate that they are providing sufficient
      community benefit. With increased public attention, hospitals need to ensure they
      are publicly documenting the benefit they provide their communities in order to
      reduce the risk that lawmakers could change the law or the IRS could revise the
      community benefit standard.

PMID- 19097606
TI  - Schedule H: what hospitals should do to prepare.
AB  - Steps hospitals should take now to prepare for Schedule H include: Form a
      multidisciplinary group to address how to meet the reporting requirements. Review
      programs currently counted as community benefit, to ensure they meet IRS
      standards. Collect community benefit data in "real time." Sharpen charity care
      policies. Consider the use of IT to facilitate charity care decisions and
      community benefit data collection. Use tax year 2008 as a dry run.

PMID- 19097607
TI  - Budgeting-or refusing to budge? How budget workshops can reduce the pain.
AB  - Elements of a successful budget workshop include: Resources committed to the
      planning process. A carefully developed workshop schedule. Classroom environment.
      Involvement of finance staff and vice presidents.

PMID- 19097608
TI  - CFOs and quality managers: bridging the disconnect.
AB  - A survey of hospitals to assess the impact of selected organizational factors on
      achieving optimal patient outcomes found several barriers. To improve clinical
      and financial outcomes healthcare organizations should: Perform a self-assessment
      and discuss different perspectives and perceptions among stakeholders. Redesign
      structures and processes that support multidisciplinary input and involvement.
      Realign roles and responsibilities. Address problem personalities. Ensure open
      lines of communication among stakeholders.

PMID- 19097609
TI  - Profit centers in clinical care departments: an idea whose time has gone.
AB  - If a hospital is to use profit centers successfully, it should resolve several
      philosophical, organizational, and accounting matters, including: How much
      decisionmaking latitude clinical care chiefs should have. Whether to take a cross
      subsidization approach. What role clinical care departments should take in a
      service line strategy.

PMID- 19097610
TI  - Gainsharing in health care: meeting the quality-of-care challenge.
AB  - In health care, most gainsharing arrangements have focused on aligning economic
      incentives between hospitals and physicians. At one time, the Office of Inspector
      General had declared such arrangements flatly illegal, but recent advisory
      opinions suggest that the OIG is taking a more lenient stance. Today, in addition
      to hospital-physician arrangements, payer-provider and payer-patient arrangements
      are viable forms of gainsharing.

PMID- 19097611
TI  - Building the business case for patient-centered care.
AB  - Hospitals that provide patient-centered care reap a number of financial benefits,
      including: Reduced length of stay. Lower cost per case. Decreased adverse events.
      Higher employee retention rates. Reduced operating costs. Decreased malpractice
      claims. Increased market share.

PMID- 19097612
TI  - Disaster planning checklist for CFOs of healthcare organizations.

PMID- 19097613
TI  - Lessons learned from extraordinary leaders.

PMID- 19097614
TI  - Healthcare IT: health plans understand the need.

PMID- 19097615
TI  - Unscrambling eggs versus improving shock absorbers.

PMID- 19097616
TI  - Trends in emergency department capacities and costs.

PMID- 19097617
TI  - James Woodburn, MD: on retail-based health clinics.

PMID- 19097618
TI  - Debating health care at long last.

PMID- 19097619
TI  - By the numbers: using data for optimal service line management.

PMID- 19097620
TI  - Breaking down barriers to electronic claims settlement.
AB  - Past attempts to transition payer and provider environments to electronic claims
      settlements have faced several obstacles. However, technological advances, the
      development of more secure databases, bank-independent approaches to electronic
      funds transfer and electronic remittance advice, and the availability of secure
      archives are now making electronic settlement increasingly practical, cost
      effective, and attainable.

PMID- 19097621
TI  - Recent developments in Medicare Part D: 7 things providers should know.
AB  - Providers should be aware of the following recent developments in the Medicare
      Part D program: The standard plan will cost more in 2007. The coverage gap will
      remain a source of discontent. The recently streamlined Drug Plan Finder eases
      decision making. The weighting method used to calculate the national average bid
      has been modified. The Part D audit guide has been finalized. Rebates and other
      price concessions face greater scrutiny. There is renewed debate over negotiated
      drug prices.

PMID- 19097622
TI  - Caring for the uninsured; a financial executive's top 10 list.
AB  - Keep apprised of relevant legislation. Examine your organization's mission and
      values. Evaluate its historical performance. Ensure senior executives are fully
      engaged with the issue. Use available reference and modeling materials. Establish
      policies and procedures in accordance with charity guidelines. Ensure accurate
      financial reporting. Identify patients' financial assistance needs early. Develop
      policies for discounts to the uninsured and underinsured. Use internal metrics to
      track performance.

PMID- 19097623
TI  - Patient financial management as a community benefit.
AB  - Steps to take in documenting medical assistance advocacy include: Designating the
      program as a social service, not a collections effort. Detailing the program's
      practices. Identifying outcomes. Sharing the impact of advocacy efforts with the
      community.

PMID- 19097624
TI  - The case for a new American healthcare system.
AB  - The U.S. healthcare system is structured on cost rather than access. The employer
      based system should be replaced with a new healthcare system that aligns with
      today's complex economic realities. Visionaries in the American business
      community need to take the lead in calling for a new healthcare system.

PMID- 19097625
TI  - Spinning straw into gold: smarter bad debt management.
AB  - To improve its bad debt management, Meridian Health focused on these three areas:
      Automatic rules-based workflow to control compliance with policies and
      procedures. Agency management and monitoring. Use of analytic technologies to
      manage recoveries.

PMID- 19097626
TI  - The revitalization of a business office: how one system increased its self-pay
      collections.
AB  - After undergoing a dramatic transformation in self-pay collections, the Health
      Alliance of Greater Cincinnati collected $34 million in 2006, up from $19 million
      in 2004. The organization was able to achieve this increase without any decrease
      in patient satisfaction.

PMID- 19097627
TI  - Patient access: a new face for the revenue cycle.
AB  - Patient access management requires skilled staff to fill the new role of patient
      representative. Unlike registrars in the past, patient representatives must
      perform a diverse and complex range of tasks, including reviewing referrals,
      obtaining authorizations, verifying eligibility, and requesting payment at time
      of service. Providing patient access staff with adequate training and ensuring
      they undergo sufficient quality assurance monitoring are critical steps to
      effective patient access management.

PMID- 19097628
TI  - Lessons learned at Parkland: how one hospital reworked its front end.
AB  - In redesigning its front-end workflow to include demographic verification and
      evaluation of patient financial need, Parkland Memorial Hospital, Dallas, learned
      the following lessons: Automation is necessary. Integrated technology provides
      significant benefits. The automated system should evaluate patient financial
      need. Front-end technology should ensure nondiscriminatory compliance with
      hospital policy. Community public relations should be maintained.

PMID- 19097629
TI  - Solving the riddle of inpatient rehabilitation coverage.
AB  - Ruling 85-2 sets forth eight criteria that, if satisfied, conclusively establish
      that an inpatient hospital rehabilitation stay is medically necessary: Close
      medical supervision by a physician with specialized training or experience in
      rehabilitation. Twenty-four hour rehabilitation nursing. Relatively intense level
      of rehabilitation services. Multidisciplinary team approach to delivery of
      program. Coordinated program of care. Significant practical improvement.
      Realistic goals. Length of rehabilitation program.

PMID- 19097630
TI  - Charity care and patient assistance fund administrative policy.

PMID- 19097631
TI  - Hiring: get it right the first time.

PMID- 19097632
TI  - E-health is the way via SOA.

PMID- 19097633
TI  - Is your capital investment strategy ready for consumerism?

PMID- 19097634
TI  - Marketing accountability: beyond ROI.

PMID- 19097635
TI  - Hospital financial results on the elevator--with a breakfast burrito.

PMID- 19097636
TI  - Uncompensated hospital care: a look at the trends.

PMID- 19097637
TI  - Psychiatric service development and suicide.

PMID- 19097638
TI  - Community mental-health services and suicide rate in Finland: a nationwide small
      area analysis.
AB  - BACKGROUND: In many countries, psychiatric services have been reformed by
      reducing the size of hospitals and developing community mental-health services.
      We investigated this reform by assessing the relation between suicide risk and
      different ways of organising mental-health services. METHODS: We did a nationwide
      comprehensive survey of Finnish adult mental-health service units between Sept 1,
      2004, and March 31, 2005. From health-care or social-care officers of 428
      municipalities, we asked for information, classified according to the European
      service mapping schedule, about adult mental-health services. For each
      municipality, we measured age-adjusted and sex-adjusted suicide risk, pooled
      between 2000 and 2004, and then adjusted for register-derived socioeconomic
      factors. FINDINGS: A wide variety of outpatient services (relative risk [RR]
      0.92, 95% CI 0.87-0.96), prominence of outpatient versus inpatient services
      (0.93, 0.89-0.97), and 24-h emergency services (0.84, 0.75-0.92) were associated
      with decreased death rates from suicide. However, after adjustment for
      socioeconomic factors, only the prominence of outpatient services was associated
      with low suicide rate (0.94, 0.90-0.98). We replicated this finding even after
      adjustment for organisational changes and inpatient treatment. INTERPRETATION:
      Well-developed community mental-health services are associated with lower suicide
      rates than are services oriented towards inpatient treatment provision. These
      data are consistent with the idea that population mental health can be improved
      by use of multifaceted, community-based, specialised mental-health services.
      FUNDING: Academy of Finland.

PMID- 19097639
TI  - Health is global: a UK Government strategy for 2008-13.

PMID- 19097640
TI  - Phospholipid decoration of microcapsules containing perfluorooctyl bromide used
      as ultrasound contrast agents.
AB  - We present here an easy method to modify the surface chemistry of polymeric
      microcapsules of perfluorooctyl bromide used as ultrasound contrast agents
      (UCAs). Capsules were obtained by a solvent emulsification-evaporation process
      with phospholipids incorporated in the organic phase before emulsification.
      Several phospholipids were reviewed: fluorescent, pegylated and biotinylated
      phospholipids. The influence of phospholipid concentration on microcapsule size
      and morphology was evaluated. Only a fraction of the phospholipids is associated
      to microcapsules, the rest being dissolved with the surfactant in the aqueous
      phase. Microscopy shows that phospholipids are present within the shell and that
      the core/shell structure is preserved up to 0.5 mg fluorescent phospholipids, up
      to about 0.25 mg pegylated phospholipids or biotinylated phospholipids (for 100
      mg of polymer, poly(lactide-co-glycolide) (PLGA)). HPLC allows quantifying
      phospholipids associated to capsules: they correspond to 10% of pegylated
      phospholipids introduced in the organic phase. The presence of pegylated lipids
      at the surface of capsules was confirmed by X-ray photon electron spectroscopy
      (XPS). The pegylation did not modify the echographic signal arising from
      capsules. Finally biotinylated microcapsules incubated with neutravidin tend to
      aggregate, which confirms the presence of biotin at the surface. These results
      are encouraging and future work will consist of nanocapsule surface modification
      for molecular imaging.

PMID- 19097641
TI  - Akt1 silencing efficiencies in lung cancer cells by sh/si/ssiRNA transfection
      using a reductable polyspermine carrier.
AB  - Efforts directed in ameliorating silencing studies with shRNA, siRNA and ssiRNA
      (siRNA with sticky overhangs) are faltered mainly due to the lack of efficient
      carrier system. In the present study, we developed reductable polyspermine (RPS)
      carrier composed of multiple spermine units with disulfide linkages for gene
      expression and silencing studies. In gene expression studies, EGFP expression was
      found to be almost 4 folds higher and 20 folds safer with RPS carrier than with
      PEI25K. Moreover, on systemic administration, RPS exhibited significantly high
      EGFP expression in mice lungs. Similarly in gene silencing studies, EGFP
      silencing achieved was nearly 1.5 times superior with RPS carrier than PEI25K.
      Also, RPS delivered Akt1 shRNA (shAkt), siRNA (siAkt) and ssiRNA (ssiAkt)
      efficiently silenced oncoprotein Akt1 and thereby decreased A549 cell survival.
      The degrees of cell survival, proliferation and metastasis were differed with the
      nature of siRNA treatment. Further study at different time intervals revealed
      that ssiAkt treatment, although superior to sh/siAkt, was highly transient while,
      shAkt treatment was uniform and prolong. These finding demonstrate the potential
      use of RPS carrier in gene expression and silencing studies, and significance of
      the nature of siRNA employed in cancer study.

PMID- 19097642
TI  - Biodegradable poly(ethylene glycol)-peptide hydrogels with well-defined structure
      and properties for cell delivery.
AB  - In this study, biodegradable PEG-peptide hydrogels have been synthesized using
      Click chemistry. A series of Arg-Gly-Asp (RGD) containing peptides were prepared
      via a solid phase synthesis approach, which were further functionalized with
      azide to yield peptide azide or peptide diazide. A tetra-hydroxy terminated 4-arm
      PEG was functionalized with acetylene and was reacted with peptide azide/diazide
      and/or PEG diazide to produce hydrogels via a copper mediated 1,3-cycloaddition
      (Click chemistry) generating a triazole linkage as the networking forming
      reaction. The gelation time ranged from 2 to 30 min, depending on temperature,
      catalyst and precursor concentration, as well as peptide structure. The resulting
      hydrogels were characterized by swelling, viscoelastic properties and morphology
      as well as their ability for cell attachment and proliferation. Hydrogels cross
      linked by peptide diazide yielded higher storage modulus (G') with shorter
      spacers between azide groups. As expected, the swelling degree decreased while
      the G' increased with increasing the concentration of the precursors as a result
      of increased cross-linking density. Primary human dermal fibroblasts were used as
      model cells to explore the possibility of using the RGD peptide hydrogels for
      cell-based wound healing. The attachment and proliferation of the cells on the
      hydrogels were evaluated. The RGD peptide hydrogels synthesized with a peptide
      concentration of 2.7-5.4mm achieved significantly improved cell attachment and
      greater cell proliferation rate when compared to the hydrogels without RGD
      peptides. These hydrogels may provide a platform technology to deliver cells for
      tissue repair.

PMID- 19097643
TI  - Collagen-phosphorylcholine interpenetrating network hydrogels as corneal
      substitutes.
AB  - A biointeractive collagen-phospholipid corneal substitute was fabricated from
      interpenetrating polymeric networks comprising 1-ethyl-3-(3-dimethyl aminopropyl)
      carbodiimide and N-hydroxysuccinimide crosslinked porcine atelocollagen, and
      poly(ethylene glycol) diacrylate crosslinked 2-methacryloyloxyethyl
      phosphorylcholine (MPC). The resulting hydrogels showed an overall increase in
      mechanical strength beyond that of either original component and enhanced
      stability against enzymatic digestion (by collagenase) or UV degradation. More
      strikingly, these hydrogels retained the full biointeractive, cell friendly
      properties of collagen in promoting corneal cell and nerve in-growth and
      regeneration (despite MPC's known anti-adhesive properties). Measurements of
      refractive indices, white light transmission and backscatter showed the optical
      properties of collagen-MPC are comparable or superior to those of the human
      cornea. In addition, the glucose and albumin permeability were comparable to
      those of human corneas. Twelve-month post-implantation results of collagen-MPC
      hydrogels into mini-pigs showed regeneration of corneal tissue (epithelium,
      stroma) as well as the tear film and sensory nerves. We also show that porcine
      collagen can be substituted with recombinant human collagen, resulting in a fully
      synthetic implant that is free from the potential risks of disease transmission
      (e.g. prions) present in animal source materials.

PMID- 19097644
TI  - Low type I cannabinoid receptor levels characterize placental villous in
      labouring delivery.

PMID- 19097645
TI  - Ecological effects of lead mining on Ozark streams: In-situ toxicity to woodland
      crayfish (Orconectes hylas).
AB  - The Viburnum Trend mining district in southeast Missouri, USA is one of the
      largest producers of lead-zinc ore in the world. Previous stream surveys found
      evidence of increased metal exposure and reduced population densities of crayfish
      immediately downstream of mining sites. We conducted an in-situ 28-d exposure to
      assess toxicity of mining-derived metals to the woodland crayfish (Orconectes
      hylas). Crayfish survival and biomass were significantly lower at mining sites
      than at reference and downstream sites. Metal concentrations in water, detritus,
      macroinvertebrates, fish, and crayfish were significantly higher at mining sites,
      and were negatively correlated with caged crayfish survival. These results
      support previous field and laboratory studies that showed mining-derived metals
      negatively affect O. hylas populations in streams draining the Viburnum Trend,
      and that in-situ toxicity testing was a valuable tool for assessing the impacts
      of mining on crayfish populations.

PMID- 19097646
TI  - Obesity, unexplained weight loss and suicide: the original Whitehall study.
AB  - BACKGROUND: Evidence on the association between obesity and suicide is mixed.
      However, the strength of obesity as a predictor of suicide may be reduced,
      because of the role of weight changes associated with mental disorders. We tested
      the hypothesis that both obesity and unexplained weight loss are related to
      elevated suicide risk. METHODS: A clinical examination with measurements of
      height, weight and self-reported unexplained weight loss was conducted at
      baseline for 18,784 men aged 40 to 69. Based on national mortality register data,
      61 suicides were identified during the 38-year follow-up. RESULTS: The age
      adjusted hazard ratio for suicide among obese versus normal weight men was 2.22
      (95% CI 0.94 to 5.28). Additional adjustment for unexplained weight loss raised
      this ratio to 2.48 (95% CI 1.04 to 5.92). Unexplained weight loss was associated
      with a substantial excess risk of suicide irrespective of obesity (age-adjusted
      hazard ratio 5.38, 95% CI 2.31 to 12.50; age- and obesity-adjusted hazard ratio
      5.58, 95% CI 2.37 to 13.13). LIMITATIONS: Inability to take into account the
      effect of depression as a potential mediating mechanism. CONCLUSIONS: This study
      provides evidence that both obesity and unexplained weight loss may be important
      predictors of suicide. Lack of adjustment for weight loss may suppress the
      observed association between obesity and suicide.

PMID- 19097647
TI  - IL-18 and IL-18 binding protein concentrations in serum and ovarian follicular
      fluid do not affect in vitro fertilization outcomes in obese, overweight, and non
      obese patients.
AB  - Obesity causes the specific upregulation of proinflammatory cytokines and
      chemokines. One of these cytokines, IL-18, has a well-known association with
      obesity. Our aim in this study was to test the effect of serum and
      intrafollicular IL-18 and IL-18 binding protein (BP) levels on in vitro
      fertilization outcomes in obese, overweight, and non-obese patients. Serum and
      pooled follicular fluid levels of IL-18, IL-18BP, and the IL-18/IL-18BP ratios
      were evaluated in 21 non-obese (body mass index [BMI] <25), 37 overweight
      (25<or=BMI<30), and 24 obese (BMI>or=30) patients undergoing in vitro
      fertilization. IL-18 and IL-18BP levels in serum and follicular fluid did not
      change with obesity. There was no correlation among serum intrafollicular IL-18,
      IL-18BP levels, and the number of oocytes retrieved and transferred, embryo
      grades or pregnancy ratios. The levels of serum and intrafollicular IL-18, IL
      18BP, and the IL-18/IL-18BP ratios do not seem to be related to in vitro
      fertilization outcomes in obese, overweight, and non-obese patients.

PMID- 19097648
TI  - Effect of body condition, body weight and adiposity on inflammatory cytokine
      responses in old horses.
AB  - Advanced age is associated with a low-grade, systemic inflammatory response
      characterized by increased inflammatory cytokine production both in vitro and in
      vivo, termed inflamm-aging. It is also known that increased white adipose tissue,
      associated with obesity, leads to increased production of inflammatory cytokines.
      To date, it is unknown whether increased adiposity contributes to the age-related
      increased inflammatory status. Here we show that peripheral blood mononuclear
      cells (PBMC) from old horses compared to young horses have increased inflammatory
      cytokine production; moreover, fat old horses compared to thin old horses have
      even greater frequencies of lymphocytes and monocytes producing inflammatory
      cytokines. Therefore, we proposed that decreasing adiposity in old horses would
      reduce age-associated increases of inflammatory cytokines both in vitro and in
      vivo, and increasing adiposity in old horses would increase these measurements.
      To test this hypothesis further, eight old obese horses (20-28 year) were
      assigned to two consecutive treatments, dietary restriction (DR) during weeks 1
      12 and increased dietary intake (DI) during weeks 13-30. Body weight, body
      condition score (BCS) and percent body fat were measured weekly. PBMC were
      stimulated in vitro and interferon gamma (IFNgamma) and tumor necrosis factor
      alpha (TNFalpha) production was measured by intracellular staining. Levels of
      nascent IFNgamma and TNFalpha mRNA expression were examined by RT-PCR. Serum
      concentrations of TNFalpha protein were also measured weekly. Reducing body
      weight and fat in old horses significantly reduced the percent of IFNgamma and
      TNFalpha positive lymphocytes and monocytes, and serum levels of TNFalpha
      protein. Further, when weight and fat increased in these old horses there was a
      significant increase in inflammatory cytokine production. Regression analysis
      also revealed significant relationships. These findings demonstrate that age
      related obesity potentially plays a role in the dysregulation of inflammatory
      cytokine production by the immune system with age or inflamm-aging in the horse.

PMID- 19097649
TI  - Taming the induced folding of drug-targeted kinases.
AB  - Kinases have been exploited as anticancer drug targets but their conformational
      plasticity hinders the progress of structure-based design because the target
      might structurally adapt in unpredictable ways upon ligand binding. Thus,
      rational design of kinase inhibitors typically avoids targeting floppy regions.
      However, the level of amino acid conservation in such regions across homologous
      kinases is relatively low compared with structured regions, making them desirable
      binding sites to control specificity. Thus, we advocate for a much needed design
      concept to target unstructured regions. This concept applies to cases in which
      the floppy region cannot sustain structure owing to deficient packing. Thus, we
      propose the design of drugs that improve the packing quality of the kinase
      structure upon association, thereby steering induced folding. This concept is
      validated by dynamically examining structural adaptations promoted by imatinib
      redesigns intended to control drug specificity.

PMID- 19097650
TI  - The beneficial effects of angiotensin-converting enzyme inhibitors on serum
      asymmetric dimethylarginine levels in the patients with cardiovascular disease.
AB  - ACEI and AT1 receptor antagonists are the drugs most consistently shown to reduce
      ADMA level in humans. Unfortunately, most of the human studies addressing the
      effect of pharmacotherapy on ADMA metabolism were accomplished on small patient
      subgroups and were relatively shortlasting. Besides, L-arginine was rarely
      measured in most studies, whereas L-arginine/ADMA ratio may be more important for
      NO synthase function than ADMA itself, and arginine concentration may be either
      increased or decreased by pharmacotherapy. We strongly believe that agents
      affecting ADMA more specifically (protein arginine methyltransferases inhibitors
      or dimethylarginine dimethylaminohydrolase inducers) deserve further
      investigation.

PMID- 19097651
TI  - Cardiac arrest caused by Barlow's syndrome or by stress cardiomyopathy?
AB  - We describe a case of out-of-hospital Cardiac Arrest (CA) in a patient with
      Barlow's Syndrome (BS) and features of Stress Cardiomyopathy (SC) (or Apical
      Ballooning Syndrome or Tako-Tsubo). The patient experienced CA during physical
      stress and was resuscitated thanks to DC-Shock. The Electrocardiogram (ECG) after
      resuscitation was unremarkable. In the reported case the documented severe
      hypokalemia, with the physical stress, could have triggered the CA, probably of
      tachyarrhythmic origin. However, in the reported case, the echocardiographic,
      coronarographic and ventriculographic features, were surprisingly
      indistinguishable from those of the SC. In conclusion it is impossible to say if,
      in our patient, the CA has been caused by BS or by SC. However, even if CA has
      been probably caused by the BS, we hypothesize that the CA, in its turn
      determined, might have caused the SC via stress mechanisms. In few words, the CA
      is a complication of SC, but should probably be regarded also as a cause of SC.

PMID- 19097652
TI  - Association of Cheyne-Stokes respiration and cardiac cachexia in congestive heart
      failure.
AB  - In patients with congestive heart failure (CHF) cachexia as well as Cheyne-Stokes
      respiration (CSR) are well known disorders. The relationship between CSR and
      cardiac cachexia however, remains unclear so far. Clinical as well as full-night
      polysomnographic data from 12 cachectic patients were compared to 13 non
      cachectic patients with CHF. The non-cachectic patients did not differ
      significantly in age (57.3+/-11.6 vs 64.8+/-14.5 years), body mass index (26.4+/
      4.0 vs 25.2+/-3.2 kg m-(2)) or ejection fraction (21.8+/-5 vs 23.3+/-7%) from
      cachectic patients. The weight loss was 2.1+/-2.3 kg in non-cachectic vs 11.5+/
      2.7 kg in cachectic patients (p<0.0001). A significant difference was detected
      for the prevalence CSR (5 vs 10 patients, p<0.03). In this study a high
      prevalence of sleep breathing disorders, in particular of CSR in CHF patients
      with cachexia was detected.

PMID- 19097653
TI  - Correlation of calcium measurement with low dose 64-slice CT and angiographic
      stenosis in patients with suspected coronary artery disease.
AB  - Coronary artery calcium is a sensitive marker of coronary artery disease (CAD).
      This study was to determine the relationship between coronary calcium score (CCS)
      and angiographic stenosis on a patient-based or vessel-based analysis. 91
      consecutive patients underwent both low dose 64-slice CT calcium scoring scan and
      conventional angiography of the heart. The total CCS of abnormal coronary
      angiogram (n=45) was 297.38+/-416.93, whereas that of normal coronary angiogram
      (n=46) was 5.37+/-9.35 (P<0.001). The CCS and degree of stenosis were moderately
      correlated on patient-based or vessel-based analysis (r=0.517, 0.521,
      respectively; both P<0.001). In conclusion, CCS could reflect the degree of
      vessel stenosis to some extent, but CCS of zero could not rule out CAD.

PMID- 19097654
TI  - Pediatric metabolic syndrome: a growing threat.
AB  - The prevalence of the metabolic syndrome (MS) is high among obese children and
      adolescents and increases with the severity of the obesity, and with central
      adiposity in particular. In addition, adverse biochemical markers of
      cardiovascular risk are already present in this population. The metabolic
      syndrome is an important risk factor for subsequent development of type 2
      diabetes and/or cardiovascular diseases. Therefore, the key clinical implication
      of a diagnosis of MS is identification of a patient needing aggressive lifestyle
      modification focused on weight reduction and increased physical activity. In
      contrast to the data from adults, long-term cardiovascular risk in children and
      adolescents with the MS has not been clearly determined.

PMID- 19097655
TI  - Synergistic effect of dual chamber pacing and disopyramide in obstructive
      hypertrophic cardiomyopathy.
AB  - This study examines acute effect of dual-chamber (DDD) pacing combined with
      disopyramide for left ventricular outflow tract (LVOT) gradient reduction in
      obstructive hypertrophic cardiomyopathy (HCM) patients. Among 24 patients
      refractory to maximal drug therapy, 7 had a significant improvement of LVOT
      gradient by DDD pacing alone. In the remaining 17 patients, the LVOT gradient
      reduction was 26+/-19% after DDD pacing alone and 35+/-16% after intravenous
      disopyramide alone. In contrast, after the combined therapy of DDD pacing and
      disopyramide, pressure gradient decreased from 102+/-35 to 28+/-23 mm Hg, a
      reduction of 72+/-21%. We have demonstrated synergy between DDD pacing and
      disopyramide for LVOT gradient reduction in obstructive HCM. Study of the long
      term effects of this combined therapy would be the next step to ascertain
      clinical utility.

PMID- 19097656
TI  - Coronary emergency and diabetes as manifestations of pheochromocytoma.
AB  - We report on a woman with refractory hypertension and diabetes suffering from
      hypertensive crises, one with chest pain suggesting acute coronary syndrome, and
      another with an abdominal pain, after which a para-aortic abdominal mass was
      diagnosed, by ultrasound, as pheochromocytoma, later confirmed by an adrenal
      scintigraphic study with (131)I-labeled metaiodobenzylguanidine. The patient was
      successfully treated with complete reversal of hypertension and diabetes. Our
      case illustrates the importance of maintaining a high index of suspicion in
      patients simultaneously presenting with an acute myocardial event and
      hypertensive crises.

PMID- 19097657
TI  - Increased beat-to-beat 'R' amplitude variability in patients with panic disorder.

PMID- 19097658
TI  - Association of diabetes with living area in Iranian women.

PMID- 19097659
TI  - Demonstration of a very rare coronary anomaly with multislice computed
      tomography: arising of right coronary artery from left anterior descending
      artery.
AB  - Arising of right coronary artery from left anterior descending artery is a very
      rare anomaly. We present a case with this anomaly that was also demonstrated with
      multislice computed tomography.

PMID- 19097660
TI  - Urethral stricture following high dose rate brachytherapy for prostate cancer.
AB  - PURPOSE: To evaluate the incidence, timing, nature and outcome of urethral
      strictures following high dose rate brachytherapy (HDRB) for prostate carcinoma.
      METHODS AND MATERIALS: Data from 474 patients with clinically localised prostate
      cancer treated with HDRB were analysed. Ninety percent received HDRB as a boost
      to external beam radiotherapy (HDRBB) and the remainder as monotherapy (HDRBM).
      Urethral strictures were graded according to the Common Terminology Criteria for
      Adverse Events v3.0. RESULTS: At a median follow-up of 41 months, 38 patients
      (8%) were diagnosed with a urethral stricture (6-year actuarial risk 12%).
      Stricture location was bulbo-membranous (BM) urethra in 92.1%. The overall
      actuarial rate of grade 2 or more BM urethral stricture was estimated at 10.8%
      (95% CI 7.0-14.9%), with a median time to diagnosis of 22 months (range 10-68
      months). All strictures were initially managed with either dilatation (n=15) or
      optical urethrotomy (n=20). Second line therapy was required in 17 cases (49%),
      third line in three cases (9%) and 1 patient open urethroplasty (grade 3
      toxicity). Predictive factors on multivariate analysis were prior trans-urethral
      resection of prostate (hazard ratio (HR) 2.81, 95% CI 1.15-6.85, p=0.023);
      hypertension (HR 2.83, 95% CI 1.37-5.85, p=0.005); and dose per fraction used in
      HDR (HR for 1 Gy increase per fraction 1.33, 95% CI 1.08-1.64, p=0.008).
      CONCLUSIONS: BM urethral strictures are the most common late grade 2 or more
      urinary toxicity following HDR brachytherapy for prostate cancer. Most are
      manageable with minimally invasive procedures. Both clinical and dosimetric
      factors appear to influence the risk of stricture formation.

PMID- 19097661
TI  - The limitation of PET imaging for biological adaptive-IMRT assessed in animal
      models.
AB  - PURPOSE: Biological image-guided radiotherapy aims at specifically irradiating
      biologically relevant sub-volumes within the tumor, as determined for instance by
      PET imaging. This approach requires that PET imaging be sensitive and specific
      enough to image various biological pathways of interest, e.g. tumor metabolism,
      proliferation and hypoxia. In this framework, a validation of PET imaging used
      for adaptive radiotherapy was undertaken in animal models by comparing small
      animal PET images (2.7mm resolution) with autoradiography (AR) (100mum
      resolution) in various tumors under various physiological situations. METHODS: A
      specific template for tumor-bearing mouse imaging has been designed (Christian,
      R&O, 2008). It allows for the registration between MRI images (Biospec, Bruker),
      FDG-PET images (Mosaic, Philips) and AR (FLA-5100, Fujifilm). After registration,
      the tumors on the PET and AR images were segmented using a threshold-based
      method. The thresholds were selected to obtain absolute equal volumes in the PET
      and AR images. Matching indexes were then calculated between the various volumes.
      The entire imaging process was performed for FSAII tumors (n=5), SCCVII (n=5) and
      irradiated (35Gy) FSAII tumors (n=5). RESULTS: In regions with high FDG activity
      delineated using high value thresholds, low matching values of 39%+/-11% (mean+/
      SD) were observed between the volumes delineated on the PET images and those
      delineated on AR. The matching values progressively increased when considering
      larger volumes obtained with lower thresholds. These findings were independent of
      tumor type, tumor metabolism or tumor size. The relationship between the matching
      values and the percentage of overall tumor volume was fitted through a power
      regression (r=0.93). As shown by simulations, the matching improved with higher
      PET resolution. The results can be extrapolated to human tumors imaged with a
      whole-body PET system. CONCLUSION: Discrepancies were found between the PET
      images and the underlying microscopic reality represented by AR images. These
      differences, attributed to the finite resolution of PET, were important when
      considering small and highly active regions of the tumors. Dose painting based on
      PET images should therefore be carefully considered and should take these
      limitations into account.

PMID- 19097662
TI  - Influence of ecophysiological factors on growth, lag phase and ochratoxin A
      production by Aspergillus niger aggregate strains in irradiated corn grains.
AB  - Ochratoxin A (OTA) is one of the most important mycotoxins of worldwide concern
      for human health. The aims of this study were to evaluate the effects of water
      activity, temperature, incubation time and their interactions on growth, lag
      phase and OTA production by two strains belonging to A. niger aggregate in
      irradiated corn grains. This study shows that OTA production on corn grains
      occurs within a more restricted range of water activity and temperature than
      fungal growth. This point is important in order to maintain the appropriate
      conditions in stored corn that prevent toxigenic fungal growth and thus OTA
      production. Irradiated corn grains were re-hydrated to 0.910-0.995 of a(W) with
      sterile distillate water. The temperatures assayed were 15, 25 and 30 degrees C.
      Growth assessment was made every day during the incubation period (21 days) to
      calculate the growth rate, lag phase and the OTA production at 7, 14 and 21 days.
      Both strains showed optimum growth at 30 degrees C at 0.951 a(W). Ochratoxin A
      production occurred over a range of temperatures (15-30 degrees C) with optimum
      production at 25 degrees C depending on a(W) assayed. Maximum OTA production was
      obtained for both strains at 0.973 a(W). The results obtained suggest that the
      storage of corn grains at water activities lower than 0.951 and 15 degrees C
      should prevent these fungal species growth and OTA production during 21 days
      approximately.

PMID- 19097663
TI  - Classical and model-based estimates of beta-cell function during a mixed meal vs.
      an OGTT in a population-based cohort.
AB  - This study compared classical and model-based beta-cell responses during an oral
      glucose tolerance test (OGTT) and a meal tolerance test (MTT) in a population
      based cohort. Individuals with normal glucose metabolism (NGM, n=161), impaired
      glucose metabolism (IGM, n=19) and type 2 diabetes mellitus (DM, n=20) underwent
      a 75 g-OGTT and an MTT (75 g carbohydrates, 50 g fat, 24 g proteins). Classical
      estimates of beta-cell function (insulinogenic index and the ratio of areas under
      insulin and glucose curves) were calculated. Mathematical modelling was used to
      determine beta-cell glucose sensitivity, rate sensitivity and potentiation.
      Insulin sensitivity was characterized by three surrogate estimates. Both
      classical and model-based estimates of beta-cell function were higher during MTT
      than during OGTT (P<0.05). Regarding the model-based parameters, especially beta
      cell sensitivity was increased following MTT as compared with OGTT (P<0.05). Both
      during OGTT and MTT, across most parameters describing beta-cell function, the
      largest reduction in beta-cell response occurred between IGM and DM, while the
      largest reduction in insulin sensitivity occurred between NGM and IGM. We
      conclude that beta-cell response is stronger after a mixed meal than after an
      OGTT with equal carbohydrate quantity, both for classical and model-based
      parameters. The higher response was mostly explained by higher beta-cell
      sensitivity during the meal.

PMID- 19097664
TI  - Relation between cardiovascular complications and blood pressure/blood glucose
      control in diabetic patients with hypertension receiving long-term candesartan
      cilexetil therapy: Challenge-DM study.
AB  - AIM: To investigate the relation between cardiovascular events and blood pressure
      or blood glucose control during long-term treatment with candesartan cilexetil in
      Japanese patients with hypertension and diabetes mellitus. METHODS: During a
      planned 3-year follow-up period, five surveys were performed (at registration,
      after 6 months, and after 1-3 years). RESULTS: Among 17,622 patients registered
      nationwide, 16,869 were available for safety evaluation and 16,860 for efficacy
      evaluation. The actual mean follow-up period was 29 months, and the annual
      incidence of primary cardiovascular events was 17.4/1000 persons. After 3 years,
      18.0% of the patients had a blood pressure <130/80 mmHg, while 45.4% had a
      hemoglobin A(1c) <6.5%. Compared with these patients showing good control of
      hypertension and/or diabetes, the incidence of cardiovascular events was
      significantly higher in patients with poor control. CONCLUSION: These findings
      emphasize the importance of tight blood pressure and glycemic control in
      hypertensive patients with diabetes. In addition, the target blood pressure
      (<130/80 mmHg) in the 2004 Japanese Hypertension Management Guidelines and the
      target hemoglobin A(1c) (<6.5%) in the Japanese Treatment Guide for Diabetes were
      supported.

PMID- 19097665
TI  - Efficacy and safety of sitagliptin in the treatment of patients with type 2
      diabetes in China, India, and Korea.
AB  - The efficacy and safety of sitagliptin as monotherapy were evaluated in Chinese,
      Indian, and Korean patients with type 2 diabetes inadequately controlled by diet
      and exercise. In a randomized, placebo-controlled, double-blind, 18-week trial,
      530 patients with HbA(1c) >or=7.5% and <or=11.0% (mean baseline 8.7%) received
      sitagliptin 100mg once daily or placebo. Compared with placebo, sitagliptin
      significantly (p<0.001) reduced mean HbA(1c) (-1.0%), fasting plasma glucose (
      1.7 mmol/L), and 2-h postprandial glucose (-3.1 mmol/L), and a significantly
      (p<0.001) greater proportion of sitagliptin-treated versus placebo-treated
      patients achieved HbA(1c) <7% (20.6% versus 5.3%, respectively) at study end.
      Efficacy of sitagliptin was demonstrated in each country. Sitagliptin was
      generally well-tolerated. Clinical adverse events (AEs) were reported in 23.3%
      and 15.2% of sitagliptin-treated and placebo-treated patients, respectively. The
      difference was primarily due to increased gastrointestinal AEs in the sitagliptin
      group, most of which were mild and resolved on study drug. Serious AEs,
      discontinuations due to AEs, and drug-related AEs occurred with a low incidence
      in both groups. No hypoglycemia was reported. In conclusion, in this study,
      sitagliptin monotherapy for 18 weeks significantly improved glycemic control and
      was well-tolerated in patients with type 2 diabetes from China, India, and Korea.

PMID- 19097666
TI  - Effects of lifestyle modification on central artery stiffness in metabolic
      syndrome subjects with pre-hypertension and/or pre-diabetes.
AB  - AIMS: To examine the effects of a 24-week lifestyle intervention prescribed by
      family doctors on carotid artery stiffness in metabolic syndrome (MS) subjects
      with pre-hypertension and/or pre-diabetes. METHODS: Sixty-three middle-aged and
      older subjects with pre-hypertension and/or pre-diabetes were divided into
      subjects without MS (MS-) and with MS (MS+). MS components and carotid artery
      stiffness by ultrasound were determined at baseline, at 8 weeks, and following
      the 24 weeks of lifestyle intervention. Family doctors prescribed an individually
      customized lifestyle prescription for aerobic exercise and Mediterranean-style
      diet. RESULTS: Carotid artery distensibility significantly increased in MS+
      following the 24 weeks of intervention compared with baseline (0.191+/-0.012 vs.
      0.143+/-0.011, 1/mmHg x 10(-2), p<0.05). Similarly, beta stiffness index
      decreased in MS+ following the 24 weeks of intervention (9.8+/-1.1 vs. 12.5+/-1.1
      AU, p<0.05). Following the intervention, waist circumference, BP and fasting
      glucose levels reduced in MS+ (all p<0.05), and 13 MS+ subjects were free from
      MS. CONCLUSIONS: The results show the reduction of carotid artery stiffness and
      the improvement of some MS components in MS subjects, suggesting a favorable
      effect of our lifestyle modification strategy on central artery stiffness as well
      as MS components in MS subjects.

PMID- 19097667
TI  - Mortality of first-time amputees in diabetics: a 10-year observation.
AB  - AIMS: We analyze mortality of first-time diabetic amputees by stratifying by
      level of amputation, differentiating short-term and long-term mortality. METHODS:
      We evaluated 277 diabetic patients who received their first lower extremity
      amputation (LEA) during 1993-97. Subjects were followed until December 2003, and
      categorized by level of amputation. We compared the mortality difference by level
      for 0-10 years, 0-10 months, and 10 months-10 years, and examined the association
      of comorbid conditions and death for each level. RESULTS: We found a significant
      difference in mortality by amputation level for 0-10 years (p<0.05) and <10
      months (p<0.01) survival, but not for the one of 10 months-10 years. For major
      amputees deceased within 10 months, sepsis was as frequent a cause of death as
      cardiovascular disease. In distal amputees, CVD, CAD and ESRD were strongly
      associated with death, but only CAD was associated death among major amputees.
      CONCLUSION: For diabetic patients undergoing first LEAs, the mortality of major
      amputees was worse than that of minor amputees due to the difference in first 10
      month mortality. The history of comorbid conditions in first-time major amputees
      was less important than in minor amputees since sepsis was the frequent cause of
      death in major amputees in this early period.

PMID- 19097668
TI  - Clinical significance and different levels of urinary monocyte chemoattractant
      protein-1 in type 2 diabetes mellitus.
AB  - OBJECTIVE: Monocyte chemoattractant protein-1(MCP-1) is a cytokine that exhibits
      most potent chemotactic activity toward monocytes. It is suggested to be
      implicated in the development and progression of diabetic nephropathy by playing
      a role in infiltration of monocyte/macrophage. Recent studies have demonstrated
      that urinary monocyte chemoattractant protein-1 (uMCP-1) is different at
      different stages of diabetic nephropathy. Based on these findings, the aim of
      this study is to examine the level of uMCP-1 and its clinical significance at
      different stages of diabetic nephropathy and at the same time to describe the
      relationship between uMCP-1 and the various parameters. METHODS: Fifty-nine cases
      with type 2 diabetes mellitus (T2DM) were divided into three groups according to
      urine albumin excretion (UAE): normal albuminuria group, microalbuminuria group
      and macroalbuminuria group. The levels of uMCP-1, protein excretion, blood urea
      nitrogen (BUN), serum creatinine (s-Cr), glycohemoglobin A1c (HbA1c), blood
      pressure and blood fat were measured in 59 patients with T2DM and 27 healthy
      adults as controls. Results Compared with normal control, levels of uMCP-1 in
      T2DM were significantly high, which were already elevated in normal albuminuria
      group. Compared with normal albuminuria group, levels of uMCP-1 in
      microalbuminuria group and macroalbuminuria group were significantly high. Levels
      of uMCP-1 in macroalbuminuria group were higher than those in microalbuminuria
      group. The level of uMCP-1 was positively correlated with UAE, systolic blood
      pressure (SBP), diastolic blood pressure (DBP), total cholesterol (TC), low
      density lipoprotein cholesterol (LDL-C) in T2DM patients, while it had no
      significant correlation with HbA1c(,) triglyceride (TG) and high density
      lipoprotein cholesterol (HDL-C). CONCLUSIONS: MCP-1 is suggested to be implicated
      in the development and progression of diabetic nephropathy. It is very important
      to measure the level of uMCP-1 in the diagnosis and intervention of early
      diabetic nephropathy.

PMID- 19097669
TI  - Obesity in the UK: a review and comparative analysis of policies within the
      devolved administrations.
AB  - In the United Kingdom obesity is a significant public problem and the formulation
      and implementation of policies to address it are primarily the responsibility of
      the devolved administrations. Containing populations which are broadly similar,
      albeit with regional differences, devolution allows for the exploration of the
      obesity policy directions the different UK countries have taken; thus providing
      opportunities for policy learning and comparison. A review and analysis of policy
      responses in the devolved administrations reveals differences in the strategic
      approaches to tackling obesity with England having recently introduced a
      population-wide strategy in contrast to the other countries. Further, policies to
      address obesity in England and Northern Ireland are being target driven in
      contrast to Scotland and Wales. In all the countries, the focus on obesity has
      been on addressing childhood obesity with Scotland having taken the lead on
      setting nutritional standards for school meals and the other countries
      subsequently following. While devolution has provided scope for the variation in
      responses to address the obesity epidemic in the UK, it is still too early to
      determine the impact of the different strategic approaches being used to tackling
      it.

PMID- 19097670
TI  - Selective pulmonary artery perfusion for the treatment of primary lung cancer:
      Improved drug exposure of the lung.
AB  - INTRODUCTION: Selective pulmonary artery perfusion (SPAP) is an experimental drug
      infusion method for the treatment of lung cancer that aims to achieve more
      effective T(umour) and lymph N(ode) down-staging. The aim of this experiment was
      to compare drug uptake of gemcitabine and carboplatin during SPAP and intravenous
      infusion (IV). MATERIAL AND METHODS: SPAP was performed in 12 pigs using
      clinically applied doses of gemcitabine (1.25g/m(2), n=4) and carboplatin (AUC 5,
      n=4) and a combination of both (n=4). All animals underwent catheterisation of
      the left pulmonary artery and furthermore a left thoracotomy and lumbotomy for
      tissue sampling. After 2min of SPAP, 30min of blood flow occlusion was performed
      in order to delay drug washout from the lung. Two additional groups were infused
      intravenously (IV) using the same dose of gemcitabine (n=4) and carboplatin
      (n=4). Peak concentrations and area under the curve (AUC) were compared with t
      tests. RESULTS: Significantly higher pulmonary gemcitabine peak concentrations
      (p<or=0.017) and AUC (p<or=0.020) were observed after SPAP gemcitabine and
      gemcitabine/carboplatin compared to IV while no differences were shown between
      serum, renal and lymph tissue. Furthermore, SPAP carboplatin and
      gemcitabine/carboplatin also resulted in significantly higher pulmonary
      carboplatin peak concentrations (p<or=0.018) compared to IV while AUC was
      significantly higher after SPAP gemcitabine/carboplatin (p=0.045). SPAP
      carboplatin resulted in significantly higher lymph concentrations at 10min
      compared to IV carboplatin (p=0.04). CONCLUSION: SPAP with gemcitabine and
      carboplatin resulted in significantly improved drug exposure of the lung compared
      to IV. Equivalent serum concentrations and a trend towards higher mediastinal
      lymph node concentrations were achieved for carboplatin. SUMMERY: Selective
      pulmonary artery perfusion (SPAP) is an experimental drug infusion method for the
      treatment of lung cancer that aims to achieve more effective T(umour) and lymph
      N(ode) down-staging. The aim of this experiment was to compare drug uptake of
      gemcitabine and carboplatin during SPAP and intravenous infusion (IV). In
      conclusion, SPAP with carboplatin and gemcitabine or the combination of both
      showed a superior uptake profile into the lung while systemic exposure was
      equivalent compared to IV. Mediastinal lymph node concentrations are comparable
      with IV or tended to be higher after SPAP with carboplatin.

PMID- 19097671
TI  - Elucidation of the biochemical pathway of 2-phenylethanol from shikimic acid
      using isolated protoplasts of rose flowers.
AB  - The isolated protoplasts of rose flowers were used to investigate the metabolic
      pathway in rose flower leading from shikimic acid or L-phenylalanine (L-Phe) to 2
      phenylethanol (2PE), a dominant volatile compound in hybrid roses such as Rosa
      damascena Mill., R. 'Hoh-Jun', and R. 'Yves Piaget'. Deuterium-labeled L-Phe
      ([2H8]L-Phe) was supplied to the protoplasts isolated from R. 'Yves Piaget'
      petals. The volatile end products ([2Hn]-2PE, n=6-8) and their related
      intermediates ([2Hn]phenylacetaldehyde, n=6-8) were detected in the protoplasts
      by gas chromatography-mass spectrometry (GC-MS). In addition, we chemically
      synthesized [2,3,4,5,6-13C5]shikimic acid, a new stable isotopomer, to
      investigate the formation of 2PE from shikimic acid by GC-MS and nuclear magnetic
      resonance. We proposed the hypothetical biochemical pathway of 2PE from shikimic
      acid via chorismic acid, L-Phe, and phenylacetaldehyde. This protoplast system
      facilitates findings of metabolic intermediates and simplifies the complex
      branching biosynthetic pathways of floral scents to distinct individual events.

PMID- 19097672
TI  - Procedural sedation goes Utstein: the Quebec guidelines.

PMID- 19097673
TI  - Absence of alpha-synuclein affects dopamine metabolism and synaptic markers in
      the striatum of aging mice.
AB  - Despite numerous evidences for neurotoxicity of overexpressed alpha-synuclein, a
      protective function was suggested for endogenous alpha-synuclein and other
      members of the synuclein family. This protective role is most important for and
      evident in presynaptic terminals, where synucleins are normally accumulated.
      However, mice lacking synucleins display no adverse phenotype. In particular, no
      significant changes in striatal dopamine metabolism and only subtle deficit of
      dopaminergic neurons in the substantia nigra were found in juvenile or adult
      mice. To assess whether aging and synuclein deficiency may have additive
      detrimental effect on the nigrostriatal system, we studied dopaminergic neurons
      of the substantia nigra and their striatal synapses in 24-26-month-old alpha
      synuclein and gamma-synuclein null mutant mice. Significant approximately 36%
      reduction of the striatal dopamine was found in aging alpha-synuclein, but not
      gamma-synuclein null mutant mice when compared to age-matching wild type mice.
      This was accompanied by the reduction of TH-positive fibers in the striatum and
      decrease of striatal levels of TH and DAT. However, no progressive loss of TH
      positive neurons was revealed in the substantia nigra of synuclein-deficient
      aging animals. Our results are consistent with a hypothesis that alpha-synuclein
      is important for normal function and integrity of synapses, and suggest that in
      the aging nervous system dysfunction of this protein could become a
      predisposition factor for the development of nigrostriatal pathology.

PMID- 19097674
TI  - Design, synthesis, and biological evaluation of novel triazole derivatives as
      inhibitors of cytochrome P450 14alpha-demethylase.
AB  - Based on the results of computational docking to the active site of the
      cytochrome P450 14alpha-demethylase (CYP51), a series of 1-(1H-1,2,4-triazole-1
      yl)-2-(2,4-difluorophenyl)-3-substituted-2-propanols as analogs of fluconazole
      were designed, synthesized, and evaluated as antifungal agents. The MIC(80)
      values indicate that compounds 1a-n exhibited higher activity against nearly all
      fungi tested except Aspergillus fumigatus than fluconazole, while compounds 2a-f,
      3a-f showed no activity or only moderate activity against all fungi tested.
      Noticeably, the MIC value of compounds 1a, 1b and 1g is 64 times lower than that
      of fluconazole against Microsporum gypseum in vitro. And compounds 1a, 1b and 2b
      showed 128 times higher activity (with the MIC(80) value of 0.0039 microg/mL)
      than that of fluconazole against Candida albicans and also showed higher activity
      than that of the other positive controls. Computational docking experiments
      indicated that the inhibition of CYP51 involves a coordination bond with iron of
      the heme group, the hydrophilic H-bonding region, the hydrophobic region, and the
      narrow hydrophobic cleft. In addition, the activity of the compounds would be
      enhanced when the side chains were shorter.

PMID- 19097676
TI  - Mental health consequences of unintended childlessness and unplanned births:
      gender differences and life course dynamics.
AB  - The discordance between fertility intentions and outcomes may be associated with
      mental health in the general population. This requires data directly linking
      individuals' fertility intentions with their outcomes. This study brings together
      two streams of research on fertility and psychological distress to examine
      whether unintended childlessness and unplanned births are associated with
      psychological distress, compared with intended childlessness and planned births.
      We also examine whether unintended childlessness and unplanned births are
      differently associated with distress at two stages of the individuals' life
      course: in early and late 30s. As women are more directly affected by the decline
      in fertility with age and the experience of motherhood is more central to women's
      identity, we also examined gender differences in these associations. Thus, we
      examined the association between four possible fertility events (planned and
      unplanned births, intended and unintended childlessness) and psychological
      distress of men and women, at two different stages over the life course (early
      and late 30s). We used longitudinal data from the US National Longitudinal Study
      of Youth 1979 (N=2524) to link individuals' fertility intentions and outcomes to
      evaluate the association of depressive symptoms (CES-D) with four possible
      fertility events occurring in two-year intervals, for men and women separately.
      Contrary to our first hypothesis, unintended childlessness and unplanned births
      were not associated with psychological distress for women. Among men, only
      unplanned births in their early 30s were associated with increases in
      psychological distress. We did not find support for our second hypothesis that
      unintended childlessness and unplanned births have a different association with
      psychological distress for men and women and as a function of the stage of life.
      These findings are discussed in the context of previous literature in this area.

PMID- 19097677
TI  - Emotions in word and face processing: early and late cortical responses.
AB  - Recent research suggests that emotion effects in word processing resemble those
      in other stimulus domains such as pictures or faces. The present study aims to
      provide more direct evidence for this notion by comparing emotion effects in word
      and face processing in a within-subject design. Event-related brain potentials
      (ERPs) were recorded as participants made decisions on the lexicality of
      emotionally positive, negative, and neutral German verbs or pseudowords, and on
      the integrity of intact happy, angry, and neutral faces or slightly distorted
      faces. Relative to neutral and negative stimuli both positive verbs and happy
      faces elicited posterior ERP negativities that were indistinguishable in scalp
      distribution and resembled the early posterior negativities reported by others.
      Importantly, these ERP modulations appeared at very different latencies.
      Therefore, it appears that similar brain systems reflect the decoding of both
      biological and symbolic emotional signals of positive valence, differing mainly
      in the speed of meaning access, which is more direct and faster for facial
      expressions than for words.

PMID- 19097679
TI  - Light cola drink is less erosive than the regular one: an in situ/ex vivo study.
AB  - OBJECTIVE: This in situ/ex vivo study assessed the erosive potential of a light
      cola drink when compared to a regular one. METHODS: During 2 experimental 14-days
      crossover phases, eight volunteers wore palatal devices with 2 human enamel
      blocks. The groups under study were: group light, erosive challenge with light
      cola drink and group regular, erosive challenge with regular cola drink. During
      14 days, erosive challenges were performed extraorally 3X/day. In each challenge,
      the device was immersed in 150ml of light cola (group light) or regular cola
      (group regular) for 5min. Erosion was analysed by surface profilometry (microm)
      and surface microhardness change (%SMH). The data were statistically analyzed
      using paired t test (p<0.05). RESULTS: Group light (0.6+/-0.2microm) showed
      significantly lesser wear than group regular (3.1+/-1.0microm). There was no
      significant difference between the groups for the %SMH (group light -63.9+/-13.9
      and group regular -78.5+/-12.7). CONCLUSIONS: The data suggest that the light
      cola drink is less erosive than the regular one.

PMID- 19097680
TI  - Interobserver, intraobserver and intrapatient reliability scores of myocardial
      strain imaging with 2-d echocardiography in patients treated with anthracyclines.
AB  - Myocardial strain imaging with 2-D echocardiography is a relatively new
      noninvasive method to assess myocardial deformation. To determine the
      interobserver, intraobserver and intrapatient reliability scores, we evaluated
      myocardial strain measurements of 10 asymptomatic survivors of childhood cancer.
      Ten patients were selected randomly out of a follow-up cohort of childhood cancer
      survivors. All 10 patients underwent a transthoracic echocardiographic
      examination. Two-dimensional gray scale images were made in parasternal apical
      four-chamber, apical two-chamber, midcavity short-axis and basal short-axis
      views. Offline analysis was performed using software for echocardiographic
      quantification (Echopac 6.1.0, GE Medical Systems, Horten, Norway). All
      echocardiographic studies were analyzed offline by three observers, separately
      (A.M., G.W., M.P.). A custom-made software package was designed for averaging the
      strain curves of three consecutive cardiac cycles. Values of peak systolic
      strain, time-to-peak strain and time-to-end systole of the different segments of
      the left ventricle were used for statistical analysis. Interobserver,
      intraobserver and intrapatient reliability were expressed as intraclass
      correlation coefficients (ICCs). Interobserver ICCs of peak strain, time to peak
      strain and time to aortic valve closure (AVC) were generally good to very good in
      all views and segments, except for in the two-chamber view. Intraobserver ICCs
      were rated as very good for almost all segments, except for the longitudinal peak
      strain values of the two-chamber view. Intrapatient ICCs were generally good for
      the two-chamber, four-chamber and midcavity short-axis views, but fair to
      moderate for the segments of the basal short-axis view (SaxMV). We recommend use
      of the four-chamber view for longitudinal peak strain values, and the basal and
      midcavity short-axis views for radial and circumferential peak strain values.
      Furthermore, we strongly recommend using the average of three cardiac cycles for
      peak strain values in clinical studies.

PMID- 19097681
TI  - Comparison of gray-scale contrast-enhanced ultrasonography with contrast-enhanced
      computed tomography in different grading of blunt hepatic and splenic trauma: an
      animal experiment.
AB  - To compare the diagnostic value of contrast-enhanced ultrasonography (CEUS) with
      contrast-enhanced computed tomography (CECT) for the detection of different
      grading of solid organ injuries in blunt abdominal trauma in animals. A self-made
      miniature tools were used as models to simulate a blunt hepatic or splenic trauma
      in 16 and 14 anesthetized dogs, respectively. Baseline ultrasound, CEUS and CECT
      were used to detect traumatic injuries of livers and spleens. The degree of
      injuries was determined by CEUS according to the American Association for the
      Surgery of Trauma (AAST) scale and the results compared with injury scale based
      on CECT evaluation. CEUS showed 22 hepatic injury sites in 16 animals and 17
      splenic injury sites in other 14 animals. According to AAST scale, 2 grade I, 4
      grade II, 3 grade III, 5 grade IV and 2 grade V hepatic lesions were present in
      16 animals; 2 grade I, 4 grade II, 6 grade III and 2 grade IV splenic lesions in
      14 animals. On CECT scan, 21 hepatic and 17 splenic injuries were demonstrated.
      According to Becker CT scaling for hepatic injury, 1 grade I, 2 grade II, 4 grade
      III, 5 grade IV and 2 grade V hepatic injuries were present. On the basis of
      Buntain spleen scaling, 2 grade I, 5 grade II, 5 grade III, 2 grade IV splenic
      injuries were showed. After Spearman rank correlation analysis, the agreement of
      CEUS with CECT on the degree of hepatic and splenic injury is 93.3% and 92.9%,
      respectively. CT is currently considered as the reference method for grading
      blunt abdominal trauma, according to experiment results, CEUS grading showed high
      levels of concordance with CECT. CEUS can accurately determine the degree of
      injury and will play an important role in clinical application.

PMID- 19097682
TI  - Performance of five phalangeal QUS parameters in the evaluation of gonadal
      status, age and vertebral fracture risk compared with DXA.
AB  - The aim of this cross-sectional study was to study the value of five different
      quantified ultrasound (QUS) parameters-amplitude-dependent speed of sound (AD
      SoS), Ultrasound Bone Profile Index (UBPI), fast-wave amplitude (FWA), bone
      transmission time (BTT) and signal dynamic (SDY)-measured at the phalanges of the
      hand in discriminating women with vertebral fracture and their relationship with
      some determinants of bone mass, in particular age and gonadal status compared
      with lumbar spine and hip dual-energy x-ray absorptiometry (DXA). We included 791
      women aged 35-84 y, divided into pre-menopause, early menopause and late
      postmenopause groups on the basis of gonadal status and years since menopause
      (YSM). The presence of vertebral fracture was evaluated radiographically. All QUS
      parameters were very sensitive to changes in early postmenopause, with a doubled
      decrease in early postmenopausal with respect to late postmenopause. In
      particular AD-SoS and BTT decreases were markedly high in the early postmenopause
      group. In the late menopause group, similar decreases were observed for AD-SoS,
      UBPI and hip bone mineral density (BMD). In the multiple logistic model, DXA and
      QUS significantly discriminate women with and without fractures (p < 0.0001);
      odds ratio (OR) was higher at lumbar spine BMD (OR 4.01), FWA (OR 3.88), AD-SoS
      (OR 3.81) and total hip BMD (OR 3.77). Even adjusting the logistic model for age,
      height, weight, lumbar spine and total hip BMD, all QUS parameters remained
      significantly predictive of vertebral fracture. AD-SoS showed the best
      performances both in terms of OR and ROC analysis. QUS parameters show a
      different behavior in evaluating the effect on bone mass of the time since
      menopause; AD-SoS and BTT showed a high sensitivity to first changes in bone
      tissue after menopause. After correction for potential confounders, AD-SoS showed
      the same ability of lumbar spine BMD in discriminating women with or without
      vertebral fractures and in the prediction of fracture risk.

PMID- 19097683
TI  - Low-intensity pulsed ultrasound for the treatment of bone delayed union or
      nonunion: a review.
AB  - The goal of this review is to present the most updated knowledge derived from
      basic science, animal studies and clinical trials, concerning biophysical
      stimulation of bone repair through low-intensity pulsed ultrasound (LIPUS), with
      particular reference to the management of delayed unions and nonunions. Low
      intensity pulsed ultrasound LIPUS has been proved to significantly stimulate and
      accelerate fresh fracture healing in animal studies and in randomized controlled
      clinical trials. LIPUS also appears as an effective and safe home treatment of
      aseptic and septic delayed-unions and nonunions, with a healing rate ranging from
      70% to 93% in different, nonrandomized, studies. Advantages of the use of this
      technology that may avoid the need for additional complex operations for the
      treatment of nonunions, include efficacy, safety, ease of use and favourable
      cost/benefit ratio. Outcomes depend on the site of nonunion, time elapsed from
      trauma, stability at the site of nonunion and host type. The detailed biophysical
      process by which low-intensity pulsed ultrasound LIPUS stimulates bone
      regeneration still remains unknown, even if various effects on bone cells in
      vitro and in vivo have been described.

PMID- 19097684
TI  - Microvascular flow estimation by microbubble-assisted Nakagami imaging.
AB  - The destruction and replenishment of microbubbles has been previously applied to
      estimating blood flow in the microcirculation. The rate of increase of the time
      intensity curve (TIC) due to microbubbles flowing into the region-of-interest
      (ROI) as measured from the conventional B-mode images reflects the flow velocity.
      In this study, we monitored microbubble replenishment using a new proposed
      approach called the time-Nakagami-parameter curve (TNC) obtained from the
      parametric image based on the Nakagami statistical parameter for quantifying the
      microvascular flow velocity. The Nakagami parameter is estimated from signal
      envelope to reflect the backscattered statistics. The feasibility of using the
      TNC to estimate the microvascular flow was explored by carrying out phantom
      measurements and in vivo animal experiments. The rates of increase of the TIC and
      TNC were quantified as the rate constants beta(I) and beta(N) of monoexponential
      fitted curves, respectively. The experimental results showed that beta(N) behaves
      similarly to the conventional beta(I) in quantifying the flow velocity. Moreover,
      the tolerance to the effects of clutter is greater for the TNC than for the TIC,
      which makes it possible to use beta(N) to differentiate various flow velocities
      even when the ROI contains nonperfused areas. This finding suggests that the TNC
      based technique can be used as a complementary tool for the conventional TIC to
      improve measurement of blood flow in the microcirculation.

PMID- 19097685
TI  - Cerebrospinal fluid-orexin levels and sleep attacks in four patients with
      Parkinson's disease.
AB  - OBJECTIVES: Sleep attacks (SAs) in Parkinson's disease (PD) are rare, but
      clinically important because they significantly impair the daily lives of
      patients. Causes of SAs include long-term activation of dopaminergic (especially
      D3) receptors. Recent studies suggest that SAs in PD may be related to impairment
      of hypothalamic orexin neurons, similar to narcolepsy. Whether orexin is
      associated with long-term activation of dopaminergic receptors remains uncertain.
      PATIENTS AND METHODS: We measured levels of orexin in samples of spinal
      cerebrospinal fluid (CSF) from 25 patients with PD, including 9 with excessive
      daytime sleepiness and 4 with SAs. Furthermore, in the four patients with SAs,
      the selective dopamine D1/D2 agonist pergolide was substituted for the causative
      drugs with D3 stimulatory activity, and CSF-orexin levels were measured before
      and after switching treatment. RESULTS: In the 25 patients with PD, including the
      4 patients with SAs, lower CSF-orexin levels were associated with a longer
      disease duration, which has been linked to a higher incidence of SAs. Switching
      treatment to pergolide significantly increased CSF-orexin levels and completely
      resolved SAs in the four patients with PD. CONCLUSION: Despite the small number
      of patients studied, our results suggest that orexin transmission is most likely
      involved in SAs in PD and that abrogation of D3 receptor stimulation may increase
      orexin and thereby inhibit SAs.

PMID- 19097686
TI  - RNA interference targeting the CD147 induces apoptosis of multi-drug resistant
      cancer cells related to XIAP depletion.
AB  - CD147 (basigin, EMMPRIN) is a widely distributed cell surface glycoprotein that
      belongs to the Ig superfamily. It is highly expressed on the surface of malignant
      tumor cells to promote their invasiveness and chemo-resistance. The present study
      aimed to reveal the anti-apoptotic effect of CD147 on the multi-drug resistant
      (MDR) phenotype of human oral squamous carcinoma cells (SCC) and its possible
      pathways. Data presented herein showed that MDR derivative SCC KB/V cell line
      expressed significantly higher CD147 and X-linked inhibitor of apoptosis (XIAP)
      than its sensitive counterpart KB cells by RT-PCR and Western blot analysis. Down
      regulation of CD147 by transfection with CD147 siRNA resulted in decreased XIAP
      expression. Flow cytometric analysis and electron microscopic observation
      revealed differential cell apoptotic status related to CD147 expression.
      Additionally, chemo-sensitivity to 5-fluorouracil of KB/V was increased by CD147
      silencing as measured by MTT colorimetric assay. These results suggest that
      inhibition of CD147 and subsequent XIAP depletion may have an anti-tumor effect
      through enhancing the susceptibility of cancer cells to apoptosis.

PMID- 19097687
TI  - Signaling components involved in Bcl-w-induced migration of gastric cancer cells.
AB  - We have previously reported that Bcl-w enhances the invasiveness of gastric
      cancer cells by inducing MMP-2 expression via phosphoinositide 3-kinase (PI3K),
      Akt and Sp1. This study demonstrates that Bcl-w additionally induces uPA
      expression and FAK activation. Analyses of the hierarchical relationship and
      functions of these components showed that the PI3K-Akt-Sp1 pathway also mediates
      the induction of uPA, and that both uPA and MMP-2 contribute to Bcl-w-induced
      invasion via the stimulation of the FAK-dependent migratory pathway. These
      findings significantly advance our understandings of the Bcl-w-induced signaling
      processes that results in the migration and invasion of cancer cells.

PMID- 19097688
TI  - Andrographolide enhances 5-fluorouracil-induced apoptosis via caspase-8-dependent
      mitochondrial pathway involving p53 participation in hepatocellular carcinoma
      (SMMC-7721) cells.
AB  - Despite recent significant advances in the treatment of human carcinoma (HCC),
      the results of chemotherapy to date remain unsatisfactory. 5-Fluorouracil (5-FU)
      still represents the cornerstone of treatment of carcinoma, and resistance to the
      actions of 5-FU is a major obstacle to successful chemotherapy. More effective
      treatment strategies may involve combinations of agents with activity against
      HCC. Andrographolide (ANDRO), a natural bicyclic diterpenoid lactone isolated
      from Andrographis paniculata, has been shown to suppress the growth of HCC cells
      and trigger apoptosis in vitro. To assess the suitability of ANDRO as a
      chemotherapeutic agent in HCC, its cytotoxic effects have been evaluated both as
      a single agent and in combination with 5-FU. ANDRO potentiates the cytotoxic
      effect of 5-FU in HCC cell line SMMC-7721 through apoptosis. ANDRO alone induces
      SMMC-7721 apoptosis with p53 expression, Bax conformation and caspase-3,8,9
      activation. Surprisingly, the addition of ANDRO to 5-FU induces synergistic
      apoptosis, which could be corroborated to the increased caspase-8, p53 activity
      and the significant changes of Bax conformation in these cells, resulting in
      increased losses of mitochondrial membrane potential, increased release of
      cytochrome c, and activation of caspase-9 and caspase-3. Suppression of caspase-8
      with the specific inhibitor z-IETD-fmk abrogates largely ANDRO/5-FU biological
      activity by preventing mitochondrial membrane potential disappearance, caspase
      3,9 activation and subsequent apoptosis. The results suggest that ANDRO may be
      effective in combination with 5-FU for the treatment of HCC cells SMMC-7721.

PMID- 19097689
TI  - Novel highly reactive and regenerable carbon/iron composites prepared from tar
      and hematite for the reduction of Cr(VI) contaminant.
AB  - Highly reactive carbon/Fe composites were prepared from tar used as a carbon
      source, and hematite (alpha-Fe(2)O(3)), a widespread naturally available iron
      oxide. Tar was impregnated on hematite and thermally treated under N(2)
      atmosphere. Mossbauer, powder X-ray diffraction and magnetization data suggested
      that treatment at 400 and 600 degrees C produced only magnetite (Fe(3)O(4))
      whereas at 800 degrees C mainly metallic iron (Fe(0)) was produced. Raman, TG and
      XRD analyses of the different composites revealed the presence of amorphous and
      graphitic carbon highly dispersed on the iron oxide surface. The composites
      obtained at 800 degrees C were very efficient in reducing aqueous Cr(VI), as
      CrO(4)(2-), even compared to finely ground commercial Fe(0). XPS and Mossbauer
      data showed that after five consecutive reuses, the composites deactivated, due
      to the surface oxidation of Fe(0). A simple treatment at 800 degrees C completely
      regenerated the composite by reducing Fe(3+) species allowing several reuses.

PMID- 19097690
TI  - Adsorption of Ni(II) on oxidized multi-walled carbon nanotubes: effect of contact
      time, pH, foreign ions and PAA.
AB  - The adsorption of Ni(II) on oxidized multi-walled carbon nanotubes (MWCNTs) as a
      function of contact time, pH and foreign ions in the absence and presence of
      polyacrylic acid (PAA) was studied using batch technique. The results indicated
      that adsorption of Ni(II) on oxidized MWCNTs increased from zero to approximately
      99% at pH 2-9, and then maintained the high level with increasing pH. Kinetic
      data showed that the adsorption process achieved equilibrium within 2h and
      experimental data were fitted well by the pseudo-second-order equation. A
      positive effect of PAA on Ni(II) adsorption was found at pH<8, whereas a negative
      effect was observed at pH>8. The effect of addition sequences of PAA/Ni(II) on
      the adsorption of Ni(II) to PAA-MWCNT hybrids were also studied. The results
      indicated that the adsorption of Ni(II) was influenced by addition sequences
      obviously. The adsorption of Ni(II) on oxidized MWCNTs may be mainly attributed
      to surface complexation and ion exchange. Oxidized MWCNTs are suitable material
      in the solidification and pre-concentration of Ni(II) from aqueous solutions.

PMID- 19097691
TI  - Removal of Pb(II) using the modified lawny grass: mechanism, kinetics,
      equilibrium and thermodynamic studies.
AB  - A series of new chemical-modified lawny grass adsorbents were prepared and the
      feasibility of absorbents to remove Pb(II) ion from aqueous solution was
      examined. The absorbents were characterized by FTIR spectra and elemental
      analysis. Kinetics, equilibrium, thermodynamics, column adsorption and mechanism
      were studied. The optimum pH is in the range of 5.0-5.8 for all adsorbents. The
      sorption system follows pseudo-second-order kinetic model and equilibrium time is
      obtained after 60 min. The maximum adsorption capacities obtained from Langmuir
      Freundlich model are 1.55 and 1.26 mol/kg by using 1 CG and 0.6 CG (lawny grass
      modified by 1 mol/L or 0.6 mol/L citric acid, respectively). Thermodynamic
      parameters such as Delta G, Delta H and DeltaS are evaluated for the adsorption
      process. The results indicates that the adsorption of Pb(II) is spontaneous and
      endothermic. The breakthrough point is achieved at 100 BV (bed volume) by a
      column of 0.6 CG. Desorption of Pb(II) and regeneration of the column is achieved
      by 0.1 mol/L HCl elution. After 3 adsorption/desorption cycles, the breakthrough
      point remains around 100 BV, which shows that grass adsorbent is regenerated
      easily and used repeatedly. Above results indicates that lawny grass have a good
      potential for removal of lead from dilute aqueous solution in the future.

PMID- 19097693
TI  - The use of EAF dust in cement composites: assessment of environmental impact.
AB  - Electric arc filter dust (EAF dust) is a waste by-product which occurs in the
      production of steel. Instead of being disposed of, it can be used in cement
      composites for civil engineering, and for balances in washing machines. To
      estimate the environmental impact of the use of EAF dust in cement composites
      leachability tests based on diffusion were performed using water and salt water
      as leaching agents. Compact and ground cement composites, and cement composites
      with addition of 1.5% of EAF dust by mass were studied. The concentrations of
      total Cr and Cr(VI) were determined in leachates over a time period of 175 days.
      At the end of the experiment the concentrations of some other metals were also
      determined in leachates. The results indicated that Cr in leachates was present
      almost solely in its hexavalent form. No leaching of Cr(VI) was observed in
      aqueous leachates from compact cement composites and compact cement composites to
      which different quantities of EAF dust have been added. In ground cement
      composites and in ground cement composites with addition of EAF dust, Cr(VI) was
      leached with water in very low concentrations up to 5 microg L(-1). Cr(VI)
      concentrations were higher in salt water leachates. In compact and ground cement
      composites with addition of EAF dust Cr(VI) concentrations were 40 and 100 microg
      L(-1), respectively. It was experimentally found that addition of EAF dust had
      almost no influence on leaching of Cr(VI) from cement composites. Leaching of
      Cr(VI) originated primarily from cement. Leaching of other metals from composites
      investigated did not represent an environmental burden. From the physico
      mechanical and environmental aspects EAF dust can be used as a component in
      cement mixtures.

PMID- 19097692
TI  - Utilization of landfill leachate parameters for pretreatment by Fenton reaction
      and struvite precipitation--a comparative study.
AB  - This paper reports results of laboratory studies on two pretreatment methods,
      struvite precipitation using aeration with H(3)PO(4) and Fenton oxidation. These
      methods utilized specific properties of the leachate: high magnesium content (172
      mg L(-1)) for struvite precipitation and a high iron concentration (56 mg L(-1))
      for Fenton treatment. Struvite precipitation (H(3)PO(4), 700 mg L(-1)) removed
      36% of NH(3)-N and 24% of SCOD. Fenton treatment (at pH 3.5) required 650 mg L(
      1) of H(2)O(2) and removed 66% of SCOD. The effect of each pretreatment on the
      returned activated sludge (RAS) was evaluated using respirometry. Both methods
      reduced the inhibitory effect of the leachate and substantially increased
      biokinetic parameters. The BOD(5)/SCOD ratio increased from 0.63 for raw leachate
      to 0.82 (struvite) and 0.88 (Fenton). Estimation of capital and operational costs
      of the total leachate treatment indicated that aeration with struvite
      precipitation, followed by biological treatment, would be the preferred option.

PMID- 19097694
TI  - Mitigation of TNT and Destex explosion effects using water mist.
AB  - The effects water mist has on the overpressures produced by the detonation of 50
      lb equivalent of high explosives (HE) TNT and Destex in a chamber is reported.
      The overpressures for each charge density were measured with and without mist
      preemptively sprayed into the space. A droplet analyzer was placed in the chamber
      prior to the detonation experiments to characterize the water mist used to
      mitigate the explosion overpressures. The impulse, initial blast wave, and quasi
      static overpressure measured in the blast mitigation experiments were reduced by
      as much as 40%, 36%, 35% for TNT and 43%, 25%, 33% for Destex when water mist was
      sprayed 60s prior to detonation at a concentration of 70 g/m(3) and droplet
      Sauter Mean Diameter (SMD) 54 microm. These results suggest that current water
      mist technology is a potentially promising concept for the mitigation of
      overpressure effects produced from the detonation of high explosives.

PMID- 19097695
TI  - Effect of bio-sludge concentration on the efficiency of sequencing batch reactor
      (SBR) system to treat wastewater containing Pb2+ and Ni2+.
AB  - The removal efficiency of sequencing batch reactor (SBR) system with synthetic
      industrial estate wastewater (SIEWW) containing Ni(2+) or Pb(2+) was increased
      with the increase of mixed liquor suspended solids (MLSS). But, the sludge volume
      index (SVI) of the system was increased up to higher than 100mL/g under MLSS of
      up to 4000 mg/L. Also, the effluent NO(3)(-) was decreased with the increase of
      MLSS. The heavy metals (Ni(2+) or Pb(2+)), BOD(5), COD and TKN removal
      efficiencies of SBR system with SIEWW containing 5mg/L heavy metal (Ni(2+) or
      Pb(2+)) under MLSS of 3000 mg/L were 83-85%, 96-97%, 95-96% and 83-94%,
      respectively. The increase of heavy metal (Ni(2+) or Pb(2+)) concentrations of
      SIEWW from 5 to 50mg/L were not significantly effected to both COD and BOD(5)
      removal efficiencies (they were reduced by only 4-5%), but they were strongly
      effected to both TKN and heavy metals removal efficiencies (they were reduced by
      15 and 20-30%, respectively). Both Ni(2+) and Pb(2+) could repress the growth of
      both nitrification and denitrification bacteria. And Ni(2+) was more effective
      than Pb(2+) to reduce the heavy metals removal efficiency. The SBR system could
      be applied to treat the industrial estate wastewater (IEWW) containing both
      Pb(2+) and Ni(2+) even the heavy metals concentrations was up to 5mg/L, but the
      removal efficiency was quite low and excess bio-sludge did not produce. However,
      the system efficiency could be increased with the increase of BOD(5)
      concentration of the wastewater. The Pb(2+), Ni(2+), COD, BOD(5) and TKN removal
      efficiencies of the system with IEWW containing 500 mg/L BOD(5), 5mg/L Ni(2+) and
      5mg/L Pb(2+) under HRT of 3 days were 85.68+/-0.31%, 87.03+/-0.21%, 86.0+/-0.5%,
      94.04+/-0.4% and 90.5+/-0.9%, respectively. And the effluent SRT, SS and SVI of
      the system were 44.7+/-0.6 days, 150+/-6 mg/L and 100mL/g, respectively.

PMID- 19097696
TI  - Membrane optode for mercury(II) determination in aqueous samples.
AB  - A color changeable optode for Hg(II) was prepared by the immobilization of a dye
      4-(2-pyridylazo)resorcinol (PAR) and a liquid ion-exchanger
      trioctylmethylammonium chloride (Aliquat-336) in the tri-(2-ethylhexyl) phosphate
      plasticized cellulose triacetate matrix. Hg(II) and CH(3)Hg(+) from aqueous
      samples could be quantitatively preconcentrated in this transparent optode
      producing a distinct color change (lambda(max)=520 nm) within 5 min equilibration
      time in bicarbonate aqueous medium or 30 min in natural water. Whereas optode
      sample without Aliquat-336 did not change its color corresponding to Hg-PAR
      complex on equilibrium with the same aqueous solution containing Hg(II) ions. The
      uptake of Hg(II) was found to be pH dependent with a maximum (>90%) at a pH 7.5.
      The uptake of ions like Cu(II), Fe(II), Zn(II) and Pb(II) was negligible in the
      optode where as the uptake of Cd(II) and Zn(II) ions was 10-15% at pH 7.5. The
      optode developed in the present work was studied for its analytical application
      for Hg(II) in the aqueous samples by spectrophotometry, radiotracer ((203)Hg),
      Energy Dispersive X-ray Fluorescence (EDXRF) analyses and Instrumental Neutron
      Activation Analysis (INAA). The minimum amount of Hg(II) required to produce
      detectable response by spectrophotometry, INAA and EDXRF were found to be 5.5, 1
      and 12 microg, respectively. This optode showed a linear increase in the
      absorbance at lambda(max)=520 nm over a concentration range of 0.22-1.32
      microg/mL of Hg(II) ions in aqueous solution for 5 min. The preconcentration of
      Hg(II) from large volume of aqueous solution was used to extend the lower limit
      of concentration range that can be quantified by the spectrophotometry of optode.
      It was observed that preconcentration of 11 microg Hg(II) in 100mL (0.11
      microg/mL) in aqueous samples gives a distinct color change and absorbance above
      3 sigma of the blank absorbance. The optode developed in the present work was
      found to be reusable.

PMID- 19097697
TI  - Cr(VI) concentration from batch contact/tank leaching and column percolation test
      using fly ash with additives.
AB  - Batch contact, tank leaching and column percolation tests were conducted to
      investigate the Cr(VI) concentration in the solution/leachate from two fly ashes
      (fly ash A and B) with additives. The additives used were cement, low alkalinity
      additive and Ariake clay. There are several factors influencing Cr(VI)
      concentration in solution/leachate, namely (1) properties of solid/liquid mixture
      (chemical composition, pH value, etc.), (2) cementation effect, (3) amount of
      water in contact with the solid mass (solid/liquid ratio in case of batch contact
      test), and (4) adsorption characteristics of the solid particles to Cr ions. The
      test results indicate that fly ash A has less cementation component (CaO of
      1.92%) and the amount of water in contact with the fly ash played an important
      role. As a result, Cr(VI) concentration from the column percolation test was much
      higher than that of the batch contact test. Adding Ariake clay had more effect on
      reducing Cr(VI) concentration for fly ash A than B because the pH value of the
      solution from fly ash A was lower, which provided a favorable condition for
      Cr(VI) ions to be reduced to Cr(III) and possibly to be adsorbed by clay
      particles. Fly ash B has more cementation component (7.15%) and for column
      percolation test, curing the sample for 1 week reduced Cr(VI) concentration
      significantly. The test results indicate that in engineering practice, a method
      which closely simulates the field condition should be selected to assess possible
      environmental effects and corresponding countermeasure methods.

PMID- 19097698
TI  - Azo dyes decomposition on new nitrogen-modified anatase TiO2 with high
      adsorptivity.
AB  - New vis active photocatalyst was obtained by the modification of commercial
      anatase TiO2 (Police, Poland) in pressure reactor in an ammonia water atmosphere
      at 100 degrees C for 4h. The photocatalytic activity of new material was tested
      during three azo dyes decomposition: monoazo (Reactive Read), diazo (Reactive
      Black) and poliazodye (Direct Green). Obtained photocatalyst had new bands at
      1430-1440 cm(-1) attributed to the bending vibrations of NH(4)(+) and at 1535 cm(
      1) associated with NH(2) groups or NO(2) and NO. UV-vis/DR spectra of
      photocatalyst had also insignificant decrease in visible region. Fluorescence
      technique was used for studying the amount of hydroxyl radicals produced on TiO2
      surface during visible light irradiation. The hydroxyl radicals produced react
      with coumarin present in the solution to form 7-hydroxycoumarin which has
      fluorescent capacity. Photocatalytic activity of modified TiO2 was compared with
      commercial titanium dioxide P25 (Degussa, Germany). The photocatalytic activity
      of TiO2/N was higher than that of unmodified material and P25 under visible light
      irradiation. The ability for dye adsorption (Reactive Red) on photocatalyst
      surface was also tested. Unmodified TiO2 and P25 has isotherm of adsorption by
      Freundlich model, and nitrogen-modified TiO2 by Langmuir model. The presence of
      nitrogen at the surface of TiO2 significantly increased adsorption capacity of
      TiO2 as well as OH radicals formation under visible radiation.

PMID- 19097699
TI  - Recovery of ammonium nitrogen from the effluent of UASB treating poultry manure
      wastewater by MAP precipitation as a slow release fertilizer.
AB  - Magnesium ammonium phosphate hexahydrate (MgNH(4)PO(4).6H(2)O, MAP) precipitation
      was studied on up-flow anaerobic sludge blanket (UASB) pretreated poultry manure
      wastewater in a lab-scale batch study. To recover high strength of ammonium
      nitrogen (NH(4)(+)-N=1318 mg/L) from UASB effluent, three combinations of
      chemicals including MgCl(2).6H(2)O+KH(2)PO(4), MgSO(4).7H(2)O+NaHPO(4).7H(2)O,
      and MgO+85% H(3)PO(4) were first applied at the stoichiometric ratio
      (Mg(2+):NH(4)(+)-N:PO(4)(3-)-P=1:1:1) and at different pH levels ranging from
      4.45 to 11. Preliminary test results indicated that maximum NH(4)(+)-N removal,
      as well as maximum chemical oxygen demand (COD) and color reductions, were
      obtained as 85.4%, 53.3% and 49.8% at pH 9.0 with the addition of
      MgCl(2).6H(2)O+KH(2)PO(4), respectively. The paired experimental data obtained
      from batch studies were statistically evaluated by a non-parametric Mann-Whitney
      test and a two-sample t-test. Based on the previous results, another batch
      experiments were then performed at pH 9.0 using MgCl(2).6H(2)O+KH(2)PO(4) for
      different molar ratios applied as overdose (1.2:1:1, 1.5:1:1, 1:1:1.2, 1:1:1.5)
      and underdose (0.5:1:1, 0.8:1:1, 1:1:0.5, 1:1:0.8). In the final step, the
      fertility of the MAP precipitate as struvite was also tested on the growth of
      three test plants including purslane (Portulaca oleracea), garden cress (Lepidum
      sativum) and grass (Lolium perenne). Findings of this experimental study clearly
      confirmed the recovering of NH(4)(+)-N from UASB pretreated poultry manure
      wastewater by MAP precipitation, and also the application of recovered MAP sludge
      as a valuable slow release fertilizer for agricultural use.

PMID- 19097700
TI  - Differential behaviour of combustion and gasification fly ash from Puertollano
      Power Plants (Spain) for the synthesis of zeolites and silica extraction.
AB  - Coal gasification (IGCC) and pulverised coal combustion (PCC) fly ashes (FAs),
      obtained from two power plants fed with the carboniferous bituminous coal from
      Puertollano (Spain), were characterised and used as raw materials for zeolite
      synthesis by direct conversion (DC) and by alkaline fusion (Fu), and SiO2
      extraction (Si-Ex) at laboratory scale. The Puertollano FAs are characterised by
      a high SiO2 content (59%) with respect to EU coal FAs. High zeolite synthesis
      yields were obtained from both FAs by using conventional alkaline activation.
      However, the Si extraction yields were very different. The results of the zeolite
      synthesis from the Si-bearing extracts from both FAs demonstrated that high
      purity zeolites with high cation exchange capacity (CEC, between 4.3 and
      5.3meq/g) can be produced. The solid residue arising from Si-Ex is also a
      relatively high NaP1 zeolite product (CEC 2.4-2.7 meq/g) equivalent to the DC
      products. The zeolitic materials synthesised from both FAs by Fu showed an
      intermediate (between the high purity zeolites and the DC products) zeolite
      content with CEC values from 3.4 to 3.7 meq/g. Low leachable metal contents were
      obtained from high purity A and X zeolites and zeolite material synthesised by Fu
      for PCC FA.

PMID- 19097701
TI  - Poly(acrylamide) functionalized chitosan: an efficient adsorbent for azo dyes
      from aqueous solutions.
AB  - In the present communication we report on the optimization of persulfate/ascorbic
      acid initiated synthesis of chitosan-graft-poly(acrylamide) (Ch-g-PAM) and its
      application in the removal of azo dyes. The optimum yield of the copolymer was
      obtained using 16 x 10(-2)M acrylamide, 3.0 x 10(-2)M ascorbic acid, 2.4 x 10(
      3)M K(2)S(2)O(8) and 0.1g chitosan in 25 mL of 5% aqueous formic acid at 45+/-0.2
      degrees C. Ch-g-PAM remained water insoluble even under highly acidic conditions
      and could efficiently remove Remazol violet and Procion yellow dyes from the
      aqueous solutions over a pH range of 3-8 in contrast to chitosan (Ch) which
      showed pH dependent adsorption. The adsorption data of the Ch-g-PAM and Ch for
      both the dyes were modeled by Langmuir and Freundlich isotherms where the data
      fitted better to Langmuir isotherms. To understand the adsorption behavior of Ch
      g-PAM, adsorption of Remazol violet on to the copolymer was optimized and the
      kinetic and thermodynamic studies were carried out taking Ch as reference. Both
      Ch-g-PAM and Ch followed pseudo-second-order adsorption kinetics. The
      thermodynamic study revealed a positive heat of adsorption (Delta H degrees), a
      positive DeltaS degrees and a negative Delta G degrees, indicating spontaneous
      and endothermic nature of the adsorption of RV dye on to the Ch-g-PAM. The Ch-g
      PAM was found to be very efficient in removing color from real industrial
      wastewater as well, though the interfering ions present in the wastewater
      slightly hindered its adsorption capacity. The data from regeneration
      efficiencies for ten cycles evidenced the high reusability of the copolymer in
      the treatment of waste water laden with even high concentrations of dye.

PMID- 19097702
TI  - Enhancement of titania by doping rare earth for photodegradation of organic dye
      (Direct Blue).
AB  - Lanthanide ions (La(3+), Nd(3+), Sm(3+), Eu(3+), Gd(3+), and Yb(3+))/doped TiO2
      nanoparticles were successfully synthesized by sol-gel method. Their
      photocatalytic activities were evaluated using Direct Blue dye (DB53) as a
      decomposition objective. The structural features of TiO2 and lanthanide ions/TiO2
      were investigated by XRD, SEM, UV-diffuse reflectance, and nitrogen adsorption
      measurements. Our findings indicated that XRD data characteristic anatase phase
      reflections and also XRD analysis showed that lanthanides phase was not observed
      on Lanthanide ions/TiO2. The results indicated that Gd(3+)/TiO2 has the lowest
      bandgap and particle size and also the highest surface area and pore volume
      (V(p)) as well. Lanthanide ions can enhance the photocatalytic activity of TiO2
      to some extent as compared with pure TiO2 and it was found that Gd(3+)/TiO2 is
      the most effective photocatalyst. The photocatalytic tests indicate that at the
      optimum conditions; illumination time 40 min, pH approximately 4, 0.3g/L
      photocatalyst loading and 100 ppm DB53; the dye removal efficiency was 100%.
      Details of the synthesis procedure and results of the characterization studies of
      the produced lanthanide ions/TiO2 are presented in this paper.

PMID- 19097703
TI  - Hemolytic activity of Trichomonas gallinae isolates does not correspond with
      clinical virulence.
AB  - The hemolytic activity of 22 Trichomonas gallinae isolates was investigated using
      an 18h erythrocyte hemolysis assay which has been shown to correlate with the
      clinical virulence of T. vaginalis. Absorbance of the assay supernatants was
      measured at 540nm and expressed as percentage of complete hemolysis. Mean
      hemolytic activity of the T. gallinae isolates ranged from 3.5% to 53.4% and did
      not correspond with clinical virulence. The results of this investigation suggest
      hemolytic activity is not a useful in vitro virulence assay for T. gallinae.

PMID- 19097704
TI  - Impulsivity and positive psychotic symptoms influence hostility in
      methamphetamine users.
AB  - Methamphetamine (MA) use is associated with hostility, aggression, and positive
      psychotic symptoms. However, little is known of the processes or mechanisms that
      underlie this relationship. The present research was designed to investigate
      putative mediating and moderating variables between MA dependence and hostility
      in a sample of injecting MA users (N=237). Both positive symptoms of psychosis
      and higher levels of impulsivity functioned as mediators and moderators of this
      relationship. This pattern of findings suggests that MA use leads to greater
      hostility by increasing positive psychotic symptoms that contribute to a
      perception of the environment as a hostile and threatening place as well as by
      increasing impulsivity. Those who were high in positive symptoms and high in
      impulsivity were the most hostile. Individual differences in impulsivity and
      positive psychotic symptoms should be taken into account in the assessment and
      management of MA dependence.

PMID- 19097705
TI  - Test-retest reliability of an online measure of past week alcohol consumption
      (the TOT-AL), and comparison with face-to-face interview.
AB  - OBJECTIVE: This paper reports on the development of a new online measure of
      beverage-specific past week alcohol consumption (the TOT-AL), its test-retest
      reliability, and comparability with the face-to-face approach of ascertaining
      alcohol intake. METHODS: University students participating in the reliability
      study completed the TOT-AL twice on the same day with at least 3 h apart.
      Students in the comparability study attended a face-to-face interview and
      completed the TOT-AL on the same day, in a randomised order, at least 3 h apart.
      RESULTS: There was a strong correlation between the repeated measurements of the
      TOT-AL (r=0.99; 95% CI: 0.98, 0.99) and between the units calculated by the TOT
      AL and the face-to face interview (r=0.97; 95% CI: 0.95, 0.99). A high level of
      agreement between measurements was also observed in a Bland-Altman analysis.
      CONCLUSIONS: The TOT-AL is a reliable, time efficient means of ascertaining
      alcohol intake, equivalent to that obtained face-to-face. These findings support
      the use of this approach to online alcohol assessment in populations with access
      to the Internet.

PMID- 19097706
TI  - Attempts to quit smoking and relapse: factors associated with success or failure
      from the ATTEMPT cohort study.
AB  - OBJECTIVE: To identify predictors of attempts to stop smoking and predictors of
      relapse. METHODS: This study included 2431 smokers from pre-existing Internet
      panels in the United States, United Kingdom, Canada, France, and Spain. These
      panel members are Internet users who have registered voluntarily and agreed to
      participate in various online research studies. Respondents were aged 35-65
      years, smoked >or= five cigarettes per day and intended to stop smoking in the
      next 3 months. They were followed every 3 months for up to 18 months via Internet
      contact on measures relating to quit attempts, smoking status, motivation to
      quit, nicotine cue, weight and weight concern, health-related factors, withdrawal
      symptoms, and smoking cessation aids. RESULTS: In this study, recent quit
      attempts strongly predicted future attempts, but also predicted subsequent
      relapse. Motivation to quit was predictive of future attempts but not of
      relapse/abstinence following the attempts. Relapse to smoking was associated with
      nicotine dependence, exposure to smoking cues, craving, withdrawal symptoms, and
      lack of smoking cessation aids. CONCLUSIONS: The findings lend support to a model
      of cessation in which level of motivation to stop generates quit attempts but
      plays little role in relapse. Dependence, social smoking cues, and a recently
      failed quit attempt are important factors in relapse.

PMID- 19097707
TI  - Adolescent stigma towards drug addiction: effects of age and drug use behaviour.
AB  - The objective of this study was to examine adolescent age and experience with
      drug use on stigmatizing attitudes toward drug addiction. Data were derived from
      the 2005 cycle of the Ontario Student Drug Use Survey. In total, 4078, 7- to 12
      graders completed self-administered questionnaires that included a measure of
      drug abuse stigma. Results indicated that stigma scores were higher among younger
      than older adolescents, and the decline across age was robust, occurring among
      both males and females and those from rural and non-rural areas. The decline,
      however, was stronger among non-drug users and among those who had no close
      friends that use drugs. Despite the age-related decline, the level of stigma in
      general suggested that drug abuse stigma may continue into adulthood. Findings
      highlight that individual attitudes toward drug use and drug abusers are salient
      factors for personal drug use. Given that stigma is a barrier to treatment, but
      reduced stigma may encourage greater adolescent use, this study highlights the
      need for more in-depth studies of drug stigma.

PMID- 19097708
TI  - Steroid injection for lateral epicondylitis.

PMID- 19097709
TI  - When goals diverge: Staff consensus and the organizational climate.
AB  - A sample of correctional officers and prison substance abuse treatment staff
      collected by the National Criminal Justice Treatment Practices Survey is used to
      provide an exploratory study of an aspect of organizational culture consisting of
      consensus (agreement) among prison personnel regarding their beliefs about
      rehabilitation in the presence of conflicting organizational goals and aspects of
      the organizational climate important to change. Findings show that among those
      staff members responding to the survey, the belief in rehabilitation scale mean
      score was associated with higher levels of organizational commitment, and
      interdepartmental coordination. However, an hierarchical linear modeling (HLM)
      analysis that used an index score derived from the standard deviation for staff
      consensus regarding these same beliefs about rehabilitation produced a different
      pattern of results, showing that high levels of consensus were associated with
      job frustration, cynicism towards the ability of the institution to change, and
      lower levels of organizational commitment. The authors conclude that, although
      the sample may not express the beliefs of corrections officers or prison-based
      treatment staff at large, within the sample, consensus appeared to play a unique
      role in evaluating the effect of divergent goals on organizational climate as it
      relates to change, and warrants consideration when considering the effects of
      organizational climate.

PMID- 19097711
TI  - Sperm velocity and its relation to social status in Arctic charr (Salvelinus
      alpinus).
AB  - Sperm velocity has been shown to be a major determinant of fertilization success
      of external fertilizers. Yet, sperm velocity varies both within and between
      ejaculates and only a small number of fast sperm cells within an ejaculate are
      likely to have the potential of fertilizing the eggs. Having such fast cells
      should be of special importance during sperm competition, particularly for
      subordinate males that may release their sperm later or further away from eggs,
      than dominants. We examined ejaculates of dominant and subordinate male Arctic
      charr (Salvelinus alpinus), a species with sperm competition. Yet, rather than
      examining just average sperm velocity values, the aim was to examine whether the
      fastest fraction of sperm cell from dominant and subordinate males differed in
      velocity. While there was no difference in the average sperm velocity between
      dominant and subordinate males, analysis of the fastest swimming sperm cells show
      that subordinate males have significantly higher initial sperm velocity than
      dominant males within the 10, 5 and 1% fastest sperm cells. That is, the
      difference in sperm velocity between dominant and subordinate charr is most
      predominant among the fastest sperm cells. In sum, this study emphasizes the
      importance of studying the fastest sperm cells in the ejaculates, as status
      dependent differences in sperm velocity may not be detected using average values.

PMID- 19097710
TI  - Prevalence of Methicillin-resistant Staphylococcus pseudintermedius isolated from
      clinical samples of companion animals and equidaes.
AB  - In this study the prevalence of Methicillin-resistant Staphylococcus
      pseudintermedius (MRSP) in clinical specimens of different animal species was
      defined by investigating a total of 16,103 clinical samples originating from
      veterinary facilities of five German federal states in 2007. Of all samples
      examined, 72 were positive for MRSP, giving an overall prevalence of 0.45%. In
      clinical specimens originating from small animals the prevalence was 0.58% (n=67;
      dogs n=61 and cats n=6), while samples from equidaes revealed a prevalence of
      0.10% (n=5; horses n=4, donkey n=1). Forty-six representative phenotypically
      identified MRSP were further differentiated by DNA-based species assignment, PCR
      detection of mecA, SCCmec-typing and MIC determination. As expected, all 46
      isolates were unambiguously proven to be MRSP by sequencing of housekeeping genes
      pta and cpn60 and being positive for mecA. Furthermore, all isolates harboured
      the mobile staphylococcal cassette chromosome mec (SCCmec) SCCmecIII. Antibiotic
      susceptibility testing for 20 different conventional antimicrobial agents
      disclosed a high rate of multidrug-resistant isolates (45 of 46) displaying an
      identical or at least similar resistance pattern for non-beta-lactam
      antimicrobials. The recognized prevalence of MRSP, which have already been shown
      to be potential zoonotic agents, reflects the recently emerging development of
      these serious and often multidrug-resistant pathogens in Germany.

PMID- 19097712
TI  - Malformations of the epididymis, incomplete regression of the mesonephric tubules
      and hyperplasia of Leydig cells in canine persistence of Mullerian duct syndrome.
AB  - Persistence of the Mullerian duct syndrome (PMDS) is a rare form of
      pseudohermaphroditism characterized by the presence of uterus and oviducts in
      otherwise normally differentiated SRY-positive 78 XY canine males. Undescended
      testicles are also common. We report a case of a male PMDS dog with a uterus and
      bilateral cryptorchidism. The dog had an incomplete regression of the mesonephric
      tubules. As a consequence of this an abnormally enlarged head of the epididymis
      was observed. In addition, an extreme reduction in size of both the body and the
      tail was found. Microscopic examination of both testicles revealed bilateral
      hyperplasia of Leydig cells. The progesterone blood level was measured by ELISA
      and was found to be abnormally high (3.18 ng/ml) compared to that of normal male
      dogs (lower than 1 ng/ml). Three months after surgical removal of the internal
      genitalia, the serum progesterone, testosterone and oestradiol levels were normal
      for a castrated male dog.

PMID- 19097713
TI  - Determination of semen characteristics and sperm cell ultrastructure of captive
      coatis (Nasua nasua) collected by electroejaculation.
AB  - Despite the wide geographical distribution of coati (Nasua nasua) from the south
      of Canada to the north of Argentina, studies regarding the reproductive
      characteristics of this species are extremely limited. The objective of this
      study was to describe the various characteristics of coati semen by morphometric
      and ultrastructural analysis. Five mature males were anesthetized and
      electroejaculated for the collection of semen. Semen was immediately evaluated
      for color, volume, pH, sperm motility, vigor, morphology, acrosomal integrity,
      percentage of live cells and hypo-osmotic response by light microscopy. Sperm
      cell morphometry and ultrastructural analyses were also performed. Observations
      of seminal characteristics determined by electroejaculation in captive coatis
      represent a valuable baseline dataset for establishing fertility standards and
      provide background information that may be useful for assisted breeding
      programmes in members of the Procyonidae family.

PMID- 19097714
TI  - Tibolone low dose (1.25 mg/d) therapy and postural balance in elderly women.
AB  - Most hip fractures occur in subjects without osteoporosis and are associated with
      a fall. Conventional menopausal hormone therapy (HT) improves postural balance,
      which might explain the rapid reduction in hip fracture risk. It is unclear
      whether tibolone improves postural balance, which might determine its effects on
      peripheral fracture risk. OBJECTIVE: To study the short-term effects of low-dose
      tibolone therapy on postural balance in elderly women. METHODS: Eighty healthy
      women (70 evaluable), aged 60 years or more, were recruited through advertising
      in the local media. They were randomly allocated to receive either tibolone (1.25
      mg/d) or placebo for 6 months. Postural balance was assessed as sway velocity,
      using a force platform. RESULT(S): Baseline characteristics, including serum
      estradiol values and postural balance, were similar in the two study groups. On
      average, the overall dosing compliance was very high, over 97% in both groups.
      After 6 months, sway velocity had decreased (improved) by 7.6% (-0.97 cm/s;
      P=0.16 vs. baseline) in the tibolone arm and by 2.5% (-0.30 cm/s; P=0.59 vs.
      baseline) in the placebo group. The difference 0.67 cm/s was not statistically
      significant (95% CI -2.44, 1.10; P=0.45). Adjustments for age, serum estradiol
      level and variable value at baseline, revealed similar results. CONCLUSIONS:
      Short-term treatment with tibolone (1.25 mg/d), compared to placebo, did not
      significantly affect postural balance function in elderly women.

PMID- 19097715
TI  - Effect of raloxifene and low-dose percutaneous 17beta-estradiol on menopause
      symptoms and endometrium--a randomized controlled trial.
AB  - OBJECTIVE: To investigate the effects on climacteric symptoms and endometrium of
      percutaneous low-dose 17beta-estradiol associated with raloxifene in
      postmenopausal women. DESIGN: randomized placebo-controlled study. METHOD: Fifty
      two postmenopausal women with moderate to severe hot flushes were randomized to
      receive either 60 mg raloxifene (RLX; n=20), 0.5 mg percutaneous 17beta-estradiol
      associated to 60 mg raloxifene (RLX+E2; n=16) or placebo (PLC; n=16). Climacteric
      symptoms (Kupperman index) and vaginal bleeding were evaluated. At baseline and
      at the end of the study endometrial thickness was measured and endometrial
      samples were collected for histological study. RESULTS: At baseline, the mean
      Kupperman index was 23.7+/-1.8 in RLX group, 22.9+/-1.9 in RLX+E2 group and
      22.6+/-1.9 in the placebo group (NS). After 3 months, there was a significant
      reduction in Kupperman index mean values in both groups, but no statistical
      difference was observed between groups. However, RLX+E2 and placebo were
      significantly superior to RLX in reducing hot flush severity (p<0.05).
      Endometrial thickness did not change in both groups. The association of
      percutaneous low-dose 17beta-estradiol to raloxifene was not associated with
      proliferation of endometrium neither in hysteroscopies nor in endometrial
      biopsies at the third month of treatment. No vaginal bleeding was reported during
      the study. CONCLUSIONS: The association of percutaneous low dose of 17beta
      estradiol with raloxifene exerted favorable effects on hot flushes severity of
      postmenopausal women, providing a safe profile in endometrium at least in short
      term therapy.

PMID- 19097716
TI  - Morphological examination of upper airway in obstructive sleep apnea.
AB  - OBJECTIVES: An aim of this study was to assess the predictive power of an
      otorhinolaryngological examination of the upper airway to identify risk factors
      of obstructive sleep apnea syndrome (OSAS) in the patients. METHODS: We examined
      141 consecutive patients with OSAS. The morphological features were assessed by
      the designated otorhinolaryngologist while the subjects were sitting relaxedly
      with tidal breathing. The bilateral nasal resistance was measured using the
      active anterior rhinomanometry during daytime wakefulness. RESULTS: The body mass
      index (BMI), fauces's narrowness, neck circumference, lowest oxygen saturation,
      tonsil size and modified Mallampati grade (MMP) showed the statistically
      significant correlations with the apnea-hypopnea index (AHI) of an index of
      apnoeseverity, however, the age, Epworth sleepiness scale (ESS), nasal resistance
      and retroglossal space were not significantly associated with the AHI.
      CONCLUSIONS: The upper airway morphology significantly associated with AHI are
      fauces's narrowness, tonsil size, and MMP, but not nasal resistance and
      retroglossal space.

PMID- 19097717
TI  - Large asymptomatic pneumocephalus developing years after middle cranial fossa
      surgery--a case report.
AB  - Whereas acute pneumocephalus has been well characterized in the literature:
      typically seen postoperatively after neurosurgical and neurotological procedures,
      a chronic pneumocele developing several years after surgery is highly unusual.
      Most otogenic pneumocephali develop in an acute or subacute fashion, presenting
      with focal neurological symptoms, headache or signs of meningitis secondary to
      translocation of bacteria into the cavity. We describe a patient with a supra
      auricular soft-tissue swelling as the only presenting symptom of a large chronic
      epidural pneumocele with extension into the extracranial subcutaneous tissues. It
      presented several years after surgical resection of a meningioma that involved
      the temporal bone.

PMID- 19097718
TI  - CT-MR image data fusion for computer-assisted navigated surgery of orbital
      tumors.
AB  - PURPOSE: To demonstrate the value of multidetector computed tomography (MDCT) and
      magnetic resonance imaging (MRI) in the preoperative assessment of orbital
      tumors, and to present, particularly, CT and MR image data fusion for surgical
      planning and performance in computer-assisted navigated surgery of orbital
      tumors. MATERIALS AND METHODS: In this retrospective case series, 10 patients
      with orbital tumors and associated complaints underwent MDCT and MRI of the
      orbit. MDCT was performed at high resolution, with a bone window level setting in
      the axial plane. MRI was performed with an axial 3D T1-weighted (w) gradient-echo
      (GE) contrast-enhanced sequence, in addition to a standard MRI protocol. First,
      MDCT and MR images were used to diagnose tumorous lesions compared to histology
      as a standard of reference. Then, the image data sets from CT and 3D T1-w GE
      sequences were merged on a workstation to create CT-MR fusion images that were
      used for interventional planning and intraoperative image guidance. The
      intraoperative accuracy of the navigation unit was measured, defined as the
      deviation between the same landmark in the navigation image and the patient.
      Furthermore, the clinical preoperative status was compared to the patients'
      postoperative outcome. RESULTS: Radiological and histological diagnosis, which
      revealed 7 benign and 3 malignant tumors, were concordant in 7 of 10 cases (70%).
      The CT-MR fusion images supported the surgeon in the preoperative planning and
      improved the surgical performance. The mean intraoperative accuracy of the
      navigation unit was 1.35mm. Postoperatively, orbital complaints showed complete
      regression in 6 cases, were ameliorated notably in 3 cases, and remained
      unchanged in 1 case. CONCLUSION: CT and MRI are essential for the preoperative
      assessment of orbital tumors. CT-MR image data fusion is an accurate tool for
      planning the correct surgical procedure, and can improve surgical results in
      computer-assisted navigated surgery of orbital tumors.

PMID- 19097719
TI  - Development of a liquid chromatographic assay for an anti-HIV tablet containing
      lamivudine, zidovudine and TMC278.HCL.
AB  - A liquid chromatographic method was developed to analyse a tablet containing
      three anti-human immunodeficiency virus (HIV) compounds: lamivudine, zidovudine
      and a compound with the code name TMC278.HCl. Due to the presence of UV absorbing
      chromophores in the three active components, a single LC method with UV detection
      was developed. A Hypersil BDS C(18) column was used as stationary phase and the
      assay was performed with gradient elution using mobile phases containing
      acetonitrile, 0.2M potassium dihydrogen phosphate and water. The sample
      pretreatment is performed by treating the formulation with dimethyl sulfoxide
      water (1:1) followed by filtration. After method development, the influence of
      the different chromatographic parameters on the separation, the interference of
      other active compounds and excipients, the repeatability and the linearity were
      investigated. The method was shown to be robust, selective, linear and
      repeatable. Finally, the content of the compounds in the tablet was determined.

PMID- 19097721
TI  - Influence of the preparation method on the physical-chemical properties of
      ketoprofen-cyclodextrin-phosphatidylcholine ternary systems.
AB  - The aim of this work was to assess the effectiveness and actual advantages of the
      microwave (MW) technology for preparing ternary complexes of ketoprofen (Keto)
      with beta-cyclodextrin (beta-Cd) or methylated-beta-cyclodextrin (Mebeta-Cd) and
      phosphatidylcholine (EPC3) with respect to conventional preparation methods, such
      as co-grinding and sealed-heating. The products obtained with the different
      techniques were characterized by differential scanning calorimetry (DSC), X-ray
      powder diffractometry, FT-IR spectroscopy and dissolution studies. For each
      method, the influence of different experimental conditions on the physical
      chemical properties of the final products has been also investigated. DSC
      analysis was used to monitor physical stability of ternary complexes during 2
      years storage under ambient conditions. MW irradiation resulted to be a rapid and
      very convenient preparation technique. In fact, it was more effective than the
      considered conventional methods, enabling obtainment in shorter times of products
      with better performance. In particular, the Keto-Mebeta-Cd-EPC3 product prepared
      by MW treatment at 750 W for 10 min allowed achievement of about 80% of drug
      dissolution after 60 min, in comparison with the 50% and 63% values obtained for
      the corresponding products prepared by 30-min co-grinding or 60-min sealed
      heating. Moreover, such ternary products were more effective in improving drug
      dissolution than the corresponding Keto-Mebeta-Cd systems. Furthermore, the MW
      treatment at such irradiation energy enabled obtainment of totally dehydrated
      samples, which maintained unchanged solid-state characteristics and showed no
      susceptibility to ambient humidity after 2 years storage at ambient temperature.
      Therefore, MW-treated Keto-Mebeta-Cd-EPC3 systems can be successfully used for
      formulation of tablets with enhanced drug dissolution behaviour.

PMID- 19097720
TI  - Chemical profiling of Radix Paeoniae evaluated by ultra-performance liquid
      chromatography/photo-diode-array/quadrupole time-of-flight mass spectrometry.
AB  - In this study, an ultra-performance liquid chromatography/photo-diode
      array/quadrupole time-of-flight mass spectrometry (UPLC-PDA-QTOFMS) based
      chemical profiling method was established for rapid global quality evaluation of
      Radix Paeoniae. By virtue of the high resolution, high speed of UPLC and the
      accurate mass measurement of TOFMS, a total of 40 components including 29
      monoterpene glycosides, 8 galloyl glucoses and 3 phenolic compounds were
      simultaneously separated within 12min, and identified through the matching of
      empirical molecular formulae with those of published components in the in-house
      library, and were further elucidated by adjusted lower energy collision-induced
      dissociation (CID) mass spectra. Among forty components, five monoterpene
      glycoside sulfonates were identified as novel components. The established method
      was successfully applied to rapidly and globally compare the quality of Radix
      Paeoniae Alba and Radix Paeoniae Rubra, two post-harvesting handled products of
      Radix Paeoniae. Together with paeoniflorin sulfonate, five newly assigned
      monoterpene glycoside sulfonates were characteristic markers to detect non
      official sulfur dioxide gas fumigated Radix Paeoniae Alba samples. It could be
      concluded that UPLC-PDA-QTOFMS based chemical profiling is a powerful approach
      for the global quality evaluation of Radix Paeoniae as well as other herbal
      medicines.

PMID- 19097722
TI  - A generic approach for the determination of trace hydrazine in drug substances
      using in situ derivatization-headspace GC-MS.
AB  - In situ derivatization-headspace GC-MS methodology has been developed for the
      determination of hydrazine in drug substance at low ppm levels. This general
      method uses acetone or acetone-d(6) as the derivatization reagent. The resulting
      acetone azine or acetone azine-d(12) can then be analyzed by headspace GC-MS. The
      method gives excellent sensitivity with a limit of quantitation (LOQ) as low as
      0.1ppm when the API (active pharmaceutical ingredient) samples are prepared at
      10mg per headspace injection vial. The spike recoveries of hydrazine at the 1ppm
      level were between 79% and 117% in various APIs tested. The precisions (%RSD) of
      six preparations of the hydrazine standards at the concentration of 1ppm level
      were typically between 2.7 and 5.6%. A linear range of concentrations from 0.1 to
      10ppm has been demonstrated with R(2)> or =0.999. This general method has been
      tested in a number of API matrices and successfully applied to the determination
      of hydrazine in support of API batch releases and process chemistry at
      GlaxoSmithKline.

PMID- 19097724
TI  - Complications of tube thoracostomy placement in the emergency department.
AB  - BACKGROUND: Emergency medicine residents frequently perform invasive procedures,
      including tube thoracostomy (TT), that inherently place patients at risk for
      complications. OBJECTIVES: The purpose of the study was to assess the prevalence
      and types of complications from TT in an academic emergency department (ED).
      METHODS: A combined prospective and retrospective, observational study of all
      patients who had TT between December 2002 and January 2006 was performed.
      Exclusion criteria included age < 15 years and tube placement at an outside
      facility. Complications detected in the ED were defined as immediate, whereas
      those discovered later were defined as delayed. Complications requiring
      corrective surgical intervention, administration of blood products, or
      intravenous antibiotics were defined as major. Bivariate and multivariate
      analyses were used to identify operator and patient factors associated with
      complications. RESULTS: TTs were placed in 242 patients, and 90 (37%; 95%
      confidence interval [CI] 31.1-43.3%) experienced a complication. Major
      complications included one intercostal artery laceration, one retroperitoneal
      placement, and empyema in 2 patients. In multivariate analysis, blunt injury
      excluding motor vehicle accidents (odds ratio [OR] 2.57; 95% CI 1.27-5.21) and
      spontaneous pneumothorax (OR 3.84; 95% CI 1.80-8.18) were associated with all
      complications. TT size < 36 French and blunt injury excluding motor vehicle
      accidents were associated with immediate complications and spontaneous
      pneumothorax was associated with delayed complications. CONCLUSIONS: The vast
      majority of complications from TT in the ED were minor. The prevalence of
      complications was consistent with previous reports of TTs placed by non-emergency
      medicine-trained physicians outside the ED. The findings can be used to identify
      avoidable complications and improve residency training.

PMID- 19097723
TI  - Measurement of neutralising antibodies to type I interferons by gene expression
      assays specific for type 1 interferon-inducible 6-16 mRNA.
AB  - Human type I interferon products have been approved for the treatment of several
      diseases, though neutralising antibodies against them may develop and reduce
      therapeutic efficacy. Traditionally, potencies of human interferons (IFNs) and of
      neutralising antibodies (NAbs) against them are quantified by antiviral assays.
      These are being increasingly replaced by less cumbersome and faster bioassay
      methods. Since IFNs exert their biological effects by binding to receptors on
      target cells and stimulating the expression of IFN-inducible genes, measurement
      of transcribed mRNAs can form the basis of functional bioassays. In this study we
      have used two approaches, quantitative reverse transcription-polymerase chain
      reaction (qPCR) and branched DNA (bDNA), to develop efficient, sensitive and
      robust non-viral assays to quantify type I IFNs per se and NAbs in sera from
      patients treated with either IFNbeta or IFNalpha2a. We show the rapid (4h)
      induction of the type I IFN-inducible 6-16 mRNA in A549 lung carcinoma cells is
      sensitively and reproducibly concentration-dependent for both IFNbeta and
      IFNalpha2a stimulation, is quantifiable by either approach, and is readily
      adaptable for the detection and measurement of NAbs against type I IFNs.
      Quantitative neutralisation of IFN-stimulated 6-16 mRNA expression was achieved
      in both assays when sera from patients receiving IFNbeta or IFNalpha2a therapy
      known to contain NAbs against these IFNs were tested. Their rapid and potentially
      automatable performance strongly suggests these assays could be used in a
      clinical setting to monitor the development of neutralising antibodies in
      patients receiving IFN therapy.

PMID- 19097725
TI  - Omental infarction: case series and review of the literature.
AB  - BACKGROUND: Omental infarction is a rare disease entity that can cause acute or
      subacute abdominal pain. In the past, it was thought that omental infarction
      mainly occurred on the right side because it was detected when surgery was
      performed on patients who complained of abdominal pain on the right side.
      OBJECTIVE: We present this case to demonstrate that omental infarction can occur
      at any site, including the epigastric area and the lower abdomen, and even on the
      left side where the greater omentum is located. CASE REPORT: Four patients with
      omental infarction presented to the Emergency Department with various clinical
      symptoms. All of them were diagnosed by computed tomography scan. Omental
      infarction occurred on the right side in 2 patients, at the epigastric area in 1
      patient, and on the left side in 1 patient. Three were improved with supportive
      care. Laparoscopy was performed in 1 patient because his abdominal pain persisted
      despite conservative treatment. CONCLUSION: Omental infarction should be included
      in the differential diagnosis list of acute abdominal pain because it can occur
      at any site. In addition, because this disease runs a self-limited course,
      conservative care is recommended. Thus, unnecessary operations can be avoided in
      cases where omental infarction is diagnosed by imaging studies.

PMID- 19097727
TI  - Should the recommended dose of epinephrine for severe croup be changed?

PMID- 19097726
TI  - Atrial fibrillation from thyroid storm.
AB  - BACKGROUND: Thyroid storm is an often-discussed but rare presentation to
      emergency departments (EDs). The clinical presentation of a thyroid storm is the
      result of a hyperthyroid state that may result in significant morbidity or
      disability, or even death. Typically, patients are aware of their hyperthyroid
      condition, and may be able to recognize an episode of thyroid storm. However, the
      first presentation of hyperthyroidism could, in fact, be from thyrotoxic crisis.
      OBJECTIVES: To review the presentation of thyroid storm, including tachycardia,
      hyperpyrexia, agitation, and altered mental status, which can be easily
      misdiagnosed as drug intoxication. CASE REPORT: We present the case of an
      otherwise healthy young adult who was sent to the ED by an outpatient care
      provider for generalized and vague symptoms of "feeling unwell" that was
      eventually diagnosed in the ED as thyrotoxic crisis. CONCLUSION: We use this case
      to emphasize that thyrotoxic crisis should be at least considered in the
      differential diagnosis of a patient with this presentation, and to highlight how,
      even with apparently usual and effective treatments, a patient may still
      decompensate.

PMID- 19097729
TI  - Safe emergency department removal of a hardened steel penile constriction ring.
AB  - BACKGROUND: Penile constriction devices are used for the enhancement of sexual
      performance. These devices have the potential to become incarcerated, leading to
      necrosis and amputation if not removed promptly. OBJECTIVE: This article presents
      a step-by-step approach for the safe removal of a hardened steel penile
      constriction device using somewhat unorthodox tools found in a hospital. CASE
      REPORT: We present a case of an incarcerated hardened steel penile constriction
      ring that was not able to be removed with conventional techniques. We describe a
      novel technique using an electric grinder and laryngoscope blade. CONCLUSION: The
      technique described in this article is a valuable and relatively safe technique
      for the Emergency Physician to facilitate the timely removal of a hardened steel
      constriction device.

PMID- 19097728
TI  - Severe methemoglobinemia linked to gel-type topical benzocaine use: a case
      report.
AB  - BACKGROUND: Methemoglobinemia is an uncommon cause of tissue hypoxia, but it can
      be life threatening if it is not identified and treated promptly. OBJECTIVES: To
      highlight the importance of understanding the potential risks of over-the-counter
      medications, especially in unsupervised use. Topical benzocaine must be used with
      caution, even in the healthy population. CASE REPORT: We report a case of
      methemoglobinemia secondary to topical benzocaine gel. A 6-year-old boy presented
      to our Pediatric Emergency Department with cyanosis, vomiting, and lethargy after
      using a gel-type, 7.5% benzocaine (Baby Orajel) for a toothache. Physical
      examination revealed dusky blue skin, tachycardia, tachypnea, and a normal
      neurologic examination. His percutaneous oxygen saturation remained 77-83%
      despite the administration of 100% oxygen. His arterial blood sample had a dark
      chocolate color appearance, and methemoglobinemia was suspected. His
      methemoglobin level was 69.9%, which is considered a lethal level. After a single
      dose of methylene blue (1 mg/kg/dose), cyanosis was reduced and oxygenation
      improved. CONCLUSION: Over-the-counter topical benzocaine should be used with
      caution, and the presence of methemoglobinemia must be promptly identified and
      treated.

PMID- 19097730
TI  - Rocuronium vs. succinylcholine in the emergency department: a critical appraisal.
AB  - BACKGROUND: Two methods of paralysis are available for rapid sequence intubation
      (RSI) in the emergency department (ED): depolarizing agents such as
      succinylcholine, and non-depolarizing drugs such as rocuronium. Rocuronium is a
      useful alternative when succinylcholine is contraindicated. Contraindications to
      succinylcholine include allergy, history of malignant hyperthermia, denervation
      syndromes, and patients who are 24-48 h post burn or crush injury. Non
      depolarizing drugs have the advantage of causing less pain due to post-paralysis
      myalgias. CLINICAL QUESTION: Can rocuronium replace succinylcholine as the
      paralytic of choice for RSI in the ED? EVIDENCE REVIEW: Four relevant studies
      were selected from an evidence search and a structured review performed. RESULTS:
      For the outcomes of clinically acceptable intubation conditions and time to
      onset, the two agents were not statistically significantly different.
      Succinylcholine seems to produce conditions that have higher satisfaction scores.
      CONCLUSION: Succinylcholine remains the drug of choice for ED RSI unless there is
      a contraindication to its usage.

PMID- 19097731
TI  - Nitroglycerin and epinephrine improve coronary perfusion pressure in a porcine
      model of ventricular fibrillation arrest: a pilot study.
AB  - BACKGROUND: Cardiac arrest remains one of the leading causes of death worldwide.
      European Resuscitation Council Guidelines for Resuscitation 2005 recommend
      epinephrine for its treatment. OBJECTIVES: To estimate whether the administration
      of a vasodilatator such as nitroglycerin in combination with epinephrine during
      cardiopulmonary resuscitation would improve resuscitation outcome in an
      established model of ventricular fibrillation. METHODS:  DESIGN: Prospective,
      randomized, blinded, controlled study. SETTING: Animal research laboratory.
      Ventricular fibrillation was induced in 20 Landrace/Large-White pigs. It remained
      untreated for 8 min before attempting resuscitation precordial compressions,
      mechanical ventilation, and electrical defibrillation. Animals were randomized
      into two groups, 10 animals each. Group A received saline as placebo (10 mL
      dilution, bolus) and epinephrine (0.02 mg/kg). Group B received nitroglycerin (50
      microg/kg) and epinephrine (0.02 mg/kg) during cardiopulmonary resuscitation.
      Electrical defibrillation was attempted after 10 min of ventricular fibrillation.
      RESULTS: Four animals in group A restored spontaneous circulation in comparison
      to eight in Group B. Coronary perfusion pressure (p < 0.0001) was significantly
      increased in Group B during cardiopulmonary resuscitation. CONCLUSION: A
      vasodilatator, when administered in combination with a vasopressor such as
      epinephrine during cardiopulmonary resuscitation, increases coronary perfusion
      pressure.

PMID- 19097732
TI  - Differentiating low-risk and no-risk PE patients: the PERC score.
AB  - BACKGROUND: Pulmonary embolism (PE) remains one of the most challenging diagnoses
      in emergency medicine. The Pulmonary Embolism Rule-out Criteria (PERC) score, a
      decision aid to reliably distinguish low-risk from very low-risk PE patients, has
      been derived and validated. CLINICAL QUESTION: Can a subset of patients with
      sufficiently low risk for PE be identified who require no diagnostic testing?
      EVIDENCE REVIEW: The PERC score derivation and validation trials were located
      using PubMed and Web of Science. A critical appraisal of this research is
      presented. RESULTS: One single-center and another multi-center validation trial
      both confirmed that the eight-item PERC score identified a very low-risk subset
      of patients in whom PE was clinically contemplated with a negative likelihood
      ratio 0.17 (95% confidence interval 0.11-0.25) in the larger trial. If applied,
      the rule would have identified 20% of potential PE patients as very low risk.
      CONCLUSION: The PERC score provides clinicians with an easily remembered,
      validated clinical decision rule that allows physicians to forego diagnostic
      testing for pulmonary embolus in a very low-risk population.

PMID- 19097733
TI  - No opiates for headache.

PMID- 19097734
TI  - Early norepinephrine infusion delays cardiac arrest after hemorrhagic shock in
      rats.
AB  - BACKGROUND: Severe hemorrhagic shock often results in cardiac arrest due to vital
      organ hypoperfusion, especially of the heart. Although fluid resuscitation is the
      mainstay of management in hemorrhagic shock, treatment of cardiac arrest in
      association with severe hemorrhagic shock is unclear. OBJECTIVE: This study was
      designed to determine the effect of early infusion of norepinephrine on
      hemodynamics and survival in hemorrhagic shock. METHODS: Twelve Sprague-Dawley
      rats were bled to about 35% of estimated blood volume for 30 min and randomized
      to one of two groups: the study group received norepinephrine (10 microg/kg/min)
      in 5% dextrose solution (n = 6); the control group received the same volume of 5%
      dextrose (n = 6) concurrently with Lactated Ringer's solution. After 30 min of
      resuscitation, half of the shed blood was transfused in both groups. Time to
      cardiac arrest and mean arterial pressure (MAP) were compared between the two
      groups. RESULTS: MAP during the resuscitation period was higher in the
      norepinephrine group than in the control group. Five of 6 rats in the
      norepinephrine group but none of the control group survived until the transfusion
      period (83.3% vs. 0.0%, respectively; p = 0.003). Median time to cardiac arrest
      was significantly longer in the norepinephrine group (67.0 min, interquartile
      range [IQR] 60.0-77.0) than in controls (41.0 min, IQR 40.0-47.0; p = 0.002).
      CONCLUSIONS: Early use of norepinephrine in a rat model of hemorrhagic shock
      increased mean arterial pressure during the resuscitation period and delayed the
      onset of cardiac arrest.

PMID- 19097735
TI  - Posterior sternoclavicular dislocation.

PMID- 19097736
TI  - Early neurosurgical procedures enhance survival in blunt head injury: propensity
      score analysis.
AB  - BACKGROUND: Studies of trauma systems have identified traumatic brain injury as a
      frequent cause of death or disability. Due to the heterogeneity of patient
      presentations, practice variations, and potential for secondary brain injury, the
      importance of early neurosurgical procedures upon survival remains controversial.
      Traditional observational outcome studies have been biased because injury
      severity and clinical prognosis are associated with use of such interventions.
      OBJECTIVE: We used propensity analysis to investigate the clinical efficacy of
      early neurosurgical procedures in patients with traumatic brain injury. METHODS:
      We analyzed a retrospectively identified cohort of 518 consecutive patients (ages
      18-65 years) with blunt, traumatic brain injury (head Abbreviated Injury Scale
      score of >or= 3) presenting to the emergency department of a Level-1 trauma
      center. The propensity for a neurosurgical procedure (i.e., craniotomy or
      ventriculostomy) in the first 24 h was determined (based upon demographic,
      clinical presentation, head computed tomography scan findings, intracranial
      pressure monitor use, and injury severity). Multivariate logistic regression
      models for survival were developed using both the propensity for a neurosurgical
      procedure and actual performance of the procedure. RESULTS: The odds of in
      hospital death were substantially less in those patients who received an early
      neurosurgical procedure (odds ratio [OR] 0.15; 95% confidence interval [CI] 0.05
      0.41). The mortality benefit of early neurosurgical intervention persisted after
      exclusion of patients who died within the first 24 h (OR 0.13; 95% CI 0.04-0.48).
      CONCLUSIONS: Analysis of observational data after adjustment using the propensity
      score for a neurosurgical procedure in the first 24 h supports the association of
      early neurosurgical intervention and patient survival in the setting of
      significant blunt, traumatic brain injury. Transfer of at-risk head-injured
      patients to facilities with high-level neurosurgical capabilities seems
      warranted.

PMID- 19097737
TI  - An undetected humeral fracture complicating the management of anterior shoulder
      dislocation in an elderly osteoporotic patient.

PMID- 19097738
TI  - Kidney rupture after extracorporeal shockwave lithotripsy: report of a case.
AB  - BACKGROUND: Complications of extracorporeal shockwave lithotripsy (ESWL) occur in
      a small number of patients, although serious injury is rare. OBJECTIVE: To report
      the serious complication of kidney rupture during ESWL. CASE REPORT: A 65-year
      old man was transferred to the Emergency Department (ED) with right flank pain.
      He had undergone ESWL for the right renal stone at a regional hospital 2 days
      earlier. Flank pain developed immediately after ESWL and was not spontaneously
      relieved. Computed tomography scan performed at the regional hospital showed an
      extensive right perinephric hematoma. When the patient arrived at the ED, his
      vital signs were unstable but were stabilized with fluid resuscitation and
      transfusion. Conservative care with no nephrectomy was chosen because there was
      no evidence of active bleeding on Doppler ultrasound examination. He was
      uneventfully discharged on the 31st hospital day without further complications.
      CONCLUSION: Although it is rare, patients may present with kidney rupture or
      hypotension after ESWL.

PMID- 19097739
TI  - Have you read the Hippocratic Oath lately?

PMID- 19097740
TI  - Self-regulation and weight reduction in patients with type 2 diabetes: a pilot
      intervention study.
AB  - OBJECTIVE: To evaluate the efficacy of a self-regulation (SR) weight reduction
      intervention on weight, body mass index (BMI), glycosylated hemoglobin (HbA1c)
      (primary outcomes), exercise, nutrition and quality of life (secondary outcomes).
      METHODS: A pilot intervention (n=53) based on SR-principles consisted of a
      motivational interview, group sessions and a workbook and was evaluated against
      standard care with (n=38) and without a self-help manual (n=38). Subjects were
      overweight (BMI>27) patients with type 2 diabetes (52% female) from a Dutch
      hospital (mean age 58.14, S.D.=8.86). RESULTS: No differences in the outcomes
      were found between the intervention and control groups at 3 (T2) or 6 (T3)
      months. However, results at T2 and T3 revealed that patients with higher SR
      skills scores had lower HbA1c levels than patients with lower scores. CONCLUSION:
      The SR-intervention did not significantly influence the outcomes. This apparent
      lack of effect might, however, partly be due to high attrition rates in all
      treatment groups. SR-skills were positively related to changes in HbA1c-levels.
      PRACTICE IMPLICATIONS: Improving SR-skills of overweight diabetes type 2 patients
      may improve their glycemic control. Patients who are 'external regulators' may
      however profit more from directive than from SR-interventions.

PMID- 19097741
TI  - Five ways of being "theoretical": applications to provider-patient communication
      research.
AB  - OBJECTIVE: Analyzes the term "theoretical" as it applies to the area of provider
      patient communication research, in order to understand better at a conceptual
      level what the term may mean for authors and critics. METHODS: Based on
      literature on provider-patient communication. RESULTS: Offers, and discusses,
      five definitions of the term "theoretical" as it applies to empirical research
      and its exposition: (1) grounding, (2) referencing, (3) design and analysis, (4)
      interpretation, and (5) impact. Each of these definitions embodies a different
      standard for evaluating the theoretical aspects of research. CONCLUSION: Although
      it is often said that research on provider-patient communication is not
      "theoretical" enough, the term is ambiguous and often applied vaguely. A
      multidimensional analysis reveals that there are several distinct ways in which
      empirical research can be strong or weak theoretically. PRACTICE IMPLICATIONS:
      Researchers, educators, editors, and reviewers could use the "Five Ways"
      framework to appraise the theory-relevant strengths and weaknesses of empirical
      research and its exposition.

PMID- 19097742
TI  - Cognitive coping and goal adjustment in people with Peripheral Arterial Disease:
      relationships with depressive symptoms.
AB  - OBJECTIVE: The aim was to study relationships between cognitive coping
      strategies, goal adjustment processes (goal disengagement and re-engagement) and
      symptoms of depression in people with Peripheral Arterial Disease (PAD). METHODS:
      The sample consisted of 88 patients with PAD. Strategies of cognitive coping,
      goal disengagement, goal re-engagement, and depression were measured by written
      questionnaires. The main statistical methods were Pearson correlations and
      Multiple Regression Analyses. RESULTS: The results showed that a ruminative and
      catastrophizing way of coping in response to the disabilities was related to more
      depressive symptoms in this group. In contrast, coping by seeking and re-engaging
      in alternative, meaningful goals was related to less depressive symptoms.
      CONCLUSION: These findings suggest that improvements in cognitive and goal
      related coping strategies might reduce the level or risk of depressive
      symptomatology. This confirms the need for specific intervention programs that
      bring about effective changes in the coping strategies of people suffering from
      PAD. PRACTICE IMPLICATIONS: As both cognitive and goal-related coping are
      generally assumed to be mechanisms that are subject to potential influence and
      change, the results of this study provide important targets for such an
      intervention.

PMID- 19097743
TI  - TEVAR following prior abdominal aortic aneurysm surgery: increased risk of
      neurological deficit.
AB  - OBJECTIVE: Evidence regarding the impact of prior abdominal aortic aneurysm (AAA)
      repair on the risk of neurological deficit after thoracic endovascular aortic
      aneurysm repair (TEVAR) is lacking. The purpose of this study was to characterize
      the risk of TEVAR-related neurological deficit in patients who previously
      underwent infrarenal AAA surgery. METHODS: Prospective maintained databases of
      patients undergoing TEVAR in the participating institutions were searched for
      patients with a history of prior AAA surgery before TEVAR. Patient and procedural
      characteristics and postoperative mortality and morbidity were subsequently
      centrally collected and systematically entered in a database. Univariate and
      multivariate logistic regression were performed associating variables with
      postoperative spinal cord ischemia (SCI). RESULTS: Seventy-two patients were
      identified that underwent TEVAR after prior AAA repair. The risk of SCI was 12.5%
      (n = 9) and significantly higher than the 1.7% risk of SCI in patients without
      prior AAA repair (relative risk [RR] 7.2, 95% confidence interval [CI] 2.6 to
      19.6, P < .0001). Symptoms of SCI completely resolved in 4 patients with prior
      AAA repair. Univariate analysis demonstrated that the following variables were
      significant predictors of SCI in patients with prior AAA repair: preoperative
      renal insufficiency (odds ratio [OR] 29.5; 95% CI 5.3-164, P < .001), increased
      length of aorta coverage by TEVAR (OR 1.1; 95% CI 1.0-1.2, P .039) and a
      lengthened time interval between prior AAA repair and TEVAR (OR 1.2; 95% CI 1.0
      1.4, P .026). Preoperative renal insufficiency was also significantly associated
      with the risk of SCI in multivariate analysis (P .011). CONCLUSION: Prior
      infrarenal AAA repair is associated with dramatic increased risk of SCI after
      TEVAR compared to patients without prior AAA surgery. Preoperative renal
      insufficiency appears to be an important predictor of SCI after TEVAR in patients
      with prior AAA repair. A thorough understanding of the risk profile in patients
      requiring TEVAR following prior AAA surgery is essential when determining
      appropriate surgical recommendations. If the diameter and rupture risk are large
      and TEVAR is indicated, the best available care should be offered for maximal
      protection of the spinal cord in these patients.

PMID- 19097745
TI  - [Management of a high risk of thrombosis patient with drug-eluting stents
      undergoing a complete gastrectomy].
AB  - We report the case of a 70-year-old patient, with two drug-eluting stents (DES),
      scheduled for a complete gastrectomy for a gastric cancer. This case underlines
      management problems regarding a patient with a high risk of DES thrombosis in
      case of AAP withdrawal and a high risk of bleeding in case of AAP maintenance. At
      this time, no evidence-based recommendation is available for clinicians to manage
      these patients. Our strategy was therefore based on platelet function monitoring
      test, which is however neither available in clinical practice nor validated to
      predict haemorrhagic risk. Several biologic tests are under study; they could be
      useful to guide perioperative management of antiplatelet therapy in the clinical
      setting of surgical patients with DES.

PMID- 19097746
TI  - [The infectious complications of sarcoidosis].
AB  - In large cohort studies, infectious complications are rarely observed in the
      course of sarcoidosis. Only small series or cases reports of infection are
      described in sarcoidosis. Most of cases are represented by opportunistic
      infection: cryptococcosis, pneumocystis, nocardiosis, histoplasmosis.
      Corticosteroids-induced immune suppression, and T-CD4 lymphopenia, are often
      present in these cases of infection, but are not the only factors.

PMID- 19097747
TI  - [Risk of infection and systemic inflammatory and/or autoimmune diseases: where do
      we stand in 2009?].

PMID- 19097748
TI  - Patterns of access to community palliative care services: a literature review.
AB  - Policies state that access to palliative care should be provided according to
      principles of equity. Such principles would include the absence of disparities in
      access to health care that are systematically associated with social advantage. A
      review of the literature a decade ago identified that patients with different
      characteristics used community palliative care services in variable ways that
      appeared inequitable. The objective of this literature review was to review
      recent literature to identify whether such variability remains. Searching
      included the use of electronic databases, scrutinizing bibliographies, and hand
      searching journals. Articles were included if they were published after 1997 (the
      date of the previous review) up to the beginning of 2008, and if they reported
      any data that investigated the characteristics of adult patients in relation to
      their relative utilization of community palliative care services, with reference
      to a comparator population. Forty-eight studies met the inclusion criteria.
      Patients still access community palliative care services in variable ways. Those
      who are older, male, from ethnic minority populations, not married, without a
      home carer, are socioeconomically disadvantaged, and who do not have cancer are
      all less likely to access community palliative care services. These studies do
      not identify the reasons for such variable access, or whether such variability is
      warranted with reference to clinical need or other factors. Studies tend to focus
      on access to specialist palliative care services without looking at the
      complexities of service use. Studies need to move beyond description of
      utilization patterns, and examine whether such patterns are inequitable, and what
      is happening in the referral or other processes that may result in such patterns.

PMID- 19097749
TI  - Moral reasoning in obsessive-compulsive disorder.
AB  - An inflated sense of responsibility often characterizes patients with obsessive
      compulsive disorder (OCD). In this study, we asked OCD patients (n=20) and
      control participants (n=18) to resolve a series of moral dilemmas embedded in
      hypothetical scenarios. Each scenario required participants to choose one of two
      undesirable courses of action, both involving loss of life. The utilitarian
      option required them to act, thereby causing the death of one person, but
      indirectly saving the lives of others whose death would otherwise have occurred.
      The other option involved no action on their part, but their failure to act
      resulted in the deaths of people. The groups did not differ significantly in the
      options chosen, or in their latencies to resolve moral dilemmas. However, within
      the OCD group, the higher patients' scores on the Responsibility Attitude Scale,
      the less likely they were to act to kill one person to save the lives of others.
      In summary, these data imply a stronger association between moral reasoning
      patterns and responsibility attitudes than to OCD per se.

PMID- 19097750
TI  - Acute phencyclidine administration reduces extracellular glutamate levels and the
      expression of synaptophysin and SNAP-25 in rat frontal cortex.

PMID- 19097751
TI  - Obsessive compulsive symptoms in the psychosis prodrome: correlates of clinical
      and functional outcome.
AB  - OBJECTIVES: Obsessive-Compulsive Disorder (OCD) is a common co-morbid condition
      in schizophrenia, associated with poor prognosis. However, the prevalence of
      obsessive compulsive symptomatology (OCS) and its relationship to outcome has not
      been evaluated in adolescents at ultra high-risk for psychosis (UHR). METHODS:
      Sixty-four UHR and 26 non-prodromal comparison (NPC) youth were ascertained using
      the Structured Interview for Prodromal Syndromes (SIPS). Participants completed
      diagnostic interviews and the Padua Inventory (Sanavio, E., 1988. Obsessions and
      compulsions: the Padua Inventory. Behav. Res. Ther. 26, 169-177.), a self-report
      measure of OCS. RESULTS: UHR youth reported significantly higher rates of OCS on
      the Padua Inventory compared to NPC youth. Clinical diagnosis of OCD (20% of
      sample) was associated with lower risk of conversion to psychosis over the follow
      up period, but was unrelated to clinical severity or psychosocial functioning.
      However, dimensional ratings of OCS were significantly associated with positive
      symptom severity, self-reported depression, and a trend toward increased suicidal
      ideation within the UHR sample. CONCLUSIONS: OCS rates in UHR youth are well
      above estimated prevalence rates in normal populations, and commensurate with
      rates of comorbidity observed in schizophrenia. Although clinical diagnosis of
      OCD was not associated with later conversion to psychosis, OCS severity in UHR
      youth was associated with more acute symptomatic presentation, including more
      severe depression and suicidality.

PMID- 19097752
TI  - Insomnia and paranoia.
AB  - Insomnia is a potential cause of anxiety, depression, and anomalies of
      experience; separate research has shown that anxiety, depression and anomalies of
      experience are predictors of paranoia. Thus insomnia may contribute to the
      formation and maintenance of persecutory ideation. The aim was to examine for the
      first time the association of insomnia symptoms and paranoia in the general
      population and the extent of insomnia in individuals with persecutory delusions
      attending psychiatric services. Assessments of insomnia, persecutory ideation,
      anxiety, and depression were completed by 300 individuals from the general
      population and 30 individuals with persecutory delusions and a diagnosis of non
      affective psychosis. Insomnia symptoms were clearly associated with higher levels
      of persecutory ideation. Consistent with the theoretical understanding of
      paranoia, the association was partly explained by the presence of anxiety and
      depression. Moderate or severe insomnia was present in more than 50% of the
      delusions group. The study provides the first direct evidence that insomnia is
      common in individuals with high levels of paranoia. It is plausible that sleep
      difficulties contribute to the development of persecutory ideation. The
      intriguing implication is that insomnia interventions for this group could have
      the added benefit of lessening paranoia.

PMID- 19097753
TI  - Metabolite changes and gender differences in schizophrenia using 3-Tesla proton
      magnetic resonance spectroscopy (1H-MRS).
AB  - A change in the glutamatergic system is thought to play an important role in the
      pathophysiology of schizophrenia. The aim of this study was to investigate the
      changes in metabolites, including glutamate (Glu), in the anterior cingulate
      cortex (ACC) and the left basal ganglia (ltBG) of patients with chronic
      schizophrenia using proton magnetic resonance spectroscopy ((1)H-MRS). In
      addition, since gender differences in this illness were known, we examined the
      effects of gender on these metabolites. The (1)H-MRS was performed on the ACC and
      ltBG of 30 patients with schizophrenia and 25 healthy individuals who acted as
      the control group. The levels of Glu, glutamine (Gln), creatine plus
      phosphocreatine (Cre), myo-inositol (mI), N-acetylaspartate (NAA), and choline
      containing compounds (Cho) were measured. Two-way analysis of variance revealed
      that the illness significantly affected the levels of Glu and mI in the ACC; both
      metabolites were lower in the patients with schizophrenia as compared to the
      control subjects. The results also revealed that gender significantly affected
      the level of Gln in the ACC and the levels of Cre and NAA in the ltBG; the level
      of Gln in the ACC were higher in male subjects versus female subjects, whereas
      Cre and NAA levels in the ltBG were lower in male subjects as compared to female
      subjects. These results confirmed a change in the glutamatergic system and
      suggested an involvement of mI in the pathophysiology of schizophrenia.

PMID- 19097754
TI  - Desmosome splitting is a primary ultrastructural change in the acantholysis of
      pemphigus.

PMID- 19097755
TI  - Tinidazole inhibitory and cidal activity against anaerobic periodontal pathogens.
AB  - The in vitro activity of tinidazole against anaerobic periodontal pathogens (25
      Prevotella buccae, 18 Prevotella denticola, 10 Prevotella intermedia, 6
      Prevotella melaninogenica, 5 Prevotella oralis, 10 Fusobacterium nucleatum and 8
      Veillonella spp.) was determined by agar dilution. MIC(90) values (minimum
      inhibitory concentration for 90% of the organisms) were 8 microg/mL for
      Veillonella spp., 4 microg/mL for P. intermedia, 2 microg/mL for P. buccae, 1
      microg/mL for Fusobacterium spp. and 0.5 microg/mL for other Prevotella spp.
      Cidal activity was studied by killing curves with tinidazole and amoxicillin
      (alone and in combination) at concentrations similar to those achieved in
      crevicular fluid (41.2 microg/mL tinidazole and 14.05 microg/mL amoxicillin)
      against an inoculum of ca. 10(7)colony-forming units/mL of four bacterial groups,
      each one composed of four different strains of the following periodontal
      isolates: Prevotella spp., Fusobacterium spp. and Veillonella spp. (anaerobes)
      and one amoxicillin-susceptible Streptococcus spp. (facultative) in a proportion
      of 1:1:1:1. When only beta-lactamase-negative Prevotella or Fusobacterium strains
      were tested, significantly higher reductions were found with amoxicillin (>4 log
      reduction at 48 h) versus controls. The presence of beta-lactamase-positive
      Prevotella spp. or F. nucleatum strains rendered amoxicillin inactive (no
      reductions at 48 h), with no differences from controls. Amoxicillin+tinidazole
      produced >3 log reduction at 24h and >4 log reduction at 48 h regardless of the
      presence or not of beta-lactamase-positive strains. The presence in crevicular
      fluid of beta-lactamases produced by beta-lactamase-positive periodontal
      pathogens may have ecological and therapeutic consequences since it may protect
      beta-lactamase-negative periodontal pathogens from amoxicillin treatment. In
      vitro, tinidazole offered high antianaerobic activity against beta-lactamase
      positive and -negative periodontal pathogens, avoiding amoxicillin inactivation.

PMID- 19097756
TI  - Fosfomycin in paediatric cancer patients: a feasible alternative to
      glycopeptides?

PMID- 19097757
TI  - Clostridium difficile infections in a Shanghai hospital: antimicrobial
      resistance, toxin profiles and ribotypes.
AB  - The incidence of Clostridium difficile infection (CDI) has risen markedly since
      2003, however data from China are limited. A 1-year study was conducted at the
      University Hospital Huashan to characterise clinical isolates of C. difficile. Of
      74 isolates, 56 were from the first episode of CDI (43 A(+)B(+) and 13 A(-)B(+)),
      5 were from recurrences and 13 were toxin-negative. No binary toxin or TcdC
      deletion was detected. All strains were susceptible to metronidazole, vancomycin,
      meropenem and piperacillin/tazobactam. Resistance to moxifloxacin, ciprofloxacin,
      levofloxacin, erythromycin, clindamycin, tetracycline, rifampicin and fusidic
      acid was found in 46.4%, 100%, 60.7%, 71.4%, 71.4%, 35.7%, 25.0% and 17.9% of the
      isolates, respectively. All moxifloxacin-resistant isolates carried a mutation in
      either gyrA, gyrB or both. Fourteen different polymerase chain reaction ribotypes
      were identified, with a specific clone (SH II) accounting for 25% of isolates. No
      isolates belonged to ribotype 027. The present study is the first systematic
      survey of clinical C. difficile isolates in China. Further surveillance is
      required to detect clustering of cases and to monitor the emergence of specific
      highly virulent clones and resistance.

PMID- 19097758
TI  - Ertapenem peritoneal fluid concentrations in adult surgical patients.
AB  - Ertapenem, a novel carbapenem, is approved for the treatment of mild to severe
      intra-abdominal infections (IAIs), although its in vivo concentrations in
      peritoneal fluid are unknown. The purpose of this study was to determine the
      peritoneal fluid concentration of ertapenem after a single 1 g intravenous dose.
      After informed consent, 21 patients (9 females and 12 males; mean+/-standard
      deviation (S.D.) age 50.2+/-17.7 years) requiring intra-abdominal surgery were
      enrolled. Plasma and peritoneal fluid samples were taken at fixed times during
      surgery. Drug concentrations were determined by high-performance liquid
      chromatography (HPLC) with ultraviolet detection. Mean+/-S.D. ertapenem
      peritoneal fluid concentrations were 64.3+/-23.4 mg/L at 1h and 31.3+/-26.5 mg/L
      at 3 h after administration. The mean tissue/plasma ratio ranged from 46.7% to
      83.1%. The mean peritoneal fluid concentrations were well above the MIC(90)
      (minimum inhibitory concentration for 90% of the organisms) for susceptible
      bacteria found in IAIs, especially Escherichia coli, viridans streptococci,
      Enterobacteriaceae, Klebsiella spp. and Bacteroides fragilis, during the entire
      sampling time. These pharmacokinetic results support the assumption that
      ertapenem might be suitable for the treatment of IAIs.

PMID- 19097759
TI  - Inability of a reserpine-based screen to identify strains overexpressing efflux
      pump genes in clinical isolates of Staphylococcus aureus.
AB  - Overexpression of efflux pump genes conferring multidrug resistance (MDR) in
      Staphylococcus aureus results in reduced susceptibility to select biocides, dyes
      and fluoroquinolones. Reserpine is commonly used as an inhibitor of MDR efflux
      pumps and previous work from our laboratory using a reserpine-based screen to
      identify clinical isolates with an efflux phenotype revealed that nearly one-half
      overexpressed norA-B-C, mepA or mdeA. The accuracy of reserpine in predicting
      efflux pump gene overexpression in clinical strains was examined in detail.
      Bloodstream isolates of S. aureus previously classified as non-effluxing strains
      by the reserpine screen underwent gene expression analysis using quantitative
      real-time reverse transcription polymerase chain reaction (qRT-PCR). The
      reserpine screen failed to identify many strains shown by qRT-PCR to overexpress
      one or more MDR efflux pump genes. Microdilution susceptibility testing with and
      without reserpine also failed to predict efflux pump activity. Although gene
      expression does not always correlate with protein translation, our results
      indicate that in clinical S. aureus isolates the use of reserpine to predict the
      contribution of efflux to reduced susceptibility is not dependable. All strains
      used in studies designed to assess MDR efflux pump gene expression in clinical
      isolates should be evaluated by a method independent of in vitro susceptibility
      testing.

PMID- 19097760
TI  - Predominance of CTX-M-15 extended spectrum beta-lactamases in diverse Escherichia
      coli and Klebsiella pneumoniae from hospital and community patients in Kuwait.

PMID- 19097761
TI  - Diversity of putative Tn5253-like elements in Streptococcus pneumoniae.
AB  - Pneumococcal resistance to tetracycline, chloramphenicol, erythromycin and
      clindamycin is often attributed to carriage of conjugative transposons of the
      Tn916 family. The less well studied conjugative transposon Tn5253 is a composite
      transposon consisting of a Tn916-like element inserted within the unrelated
      Tn5252 element, which has also been associated with chloramphenicol and
      tetracycline resistance. Here, carriage of the Tn5252 integrase (int(5252)),
      Tn5252-encoded umuC and umuD homologues and Tn916 integrase (int(916)) was
      examined among 55 clinical isolates of Streptococcus pneumoniae resistant to one
      or more of the above mentioned antibiotics. Tn5253-associated genes were common
      among the antibiotic-resistant S. pneumoniae examined, including members of
      international clones, although the spectrum of genes and resistances carried was
      diverse. Analysis of five isolates demonstrated insertion of a Tn5253-related
      element at the same chromosomal locus but sequence and restriction site
      diversity. This study shows for the first time a high degree of variability of
      Tn5253-related elements within clinical isolates of pneumococci. The fact that
      these elements are prevalent among internationally recognised pandemic clones
      warrants a more intensive investigation.

PMID- 19097762
TI  - Immunoregulatory activity of rifaximin associated with a resistant mutant of
      Bifidobacterium infantis.

PMID- 19097763
TI  - N-(2-hydroxypropyl)methacrylamide-amphotericin B (HPMA-AmB) copolymer conjugates
      as antileishmanial agents.
AB  - Leishmaniasis is a major health problem in many parts of the world, caused by
      various species of Leishmania. Amastigotes are the clinically relevant form of
      the parasite in the human host and reside in the parasitophorous vacuole within
      macrophages. Polymer-drug conjugates have been used for lysosomotropic drug
      delivery and have already shown potential in anticancer and antileishmanial
      chemotherapy. We synthesised N-(2-hydroxypropyl)methacrylamide-amphotericin B
      (HPMA-AmB) copolymer conjugates in which the AmB was attached to the polymer
      through a degradable GlyPheLeuGly linker. Antileishmanial activity was assessed
      in vitro against intracellular amastigotes in host macrophages [murine peritoneal
      exudate macrophages (PEMs), murine bone marrow-derived macrophages (BMMs) and
      differentiated THP-1 cells]. The most potent copolymers had 50% effective
      concentration (EC(50)) values of 0.03 microg/mL AmB equivalent against Leishmania
      donovani amastigotes in PEMs and BMMs and an EC(50) of 0.57 microg/mL AmB
      equivalent against L. donovani in THP-1 cells. This activity was comparable with
      free AmB (EC(50)=0.03-0.07 microg/mL against L. donovani in PEMs and BMMs and
      0.24-0.42 microg/mL against amastigotes in THP-1 cells) and Fungizone
      (EC(50)=0.04-0.07 microg/mL against amastigotes in PEMs). Conjugates also showed
      potent in vivo activity with ca. 50% inhibition of parasite burden at 1mg/kg body
      weight.

PMID- 19097764
TI  - Molecular interactions in human nail plate analysed by dielectric spectroscopy.
AB  - The influence of diabetes mellitus on dielectric properties of the human
      fingernail was measured in vitro in the alpha-dispersion region. The frequency
      dependencies of the permittivity and conductivity for the healthy and the
      diabetic nail plate revealed three separate relaxations, which were similar for
      both materials. Significant differences were observed in the values of
      permittivity at the same frequency between the healthy and the diabetic nails
      with low water content of about 0% and 3%. Results of this paper suggest that
      hyperglycemia alters the first-order structure of the nail keratin macromolecule.

PMID- 19097765
TI  - [Sleep-disordered breathing in children].
AB  - Sleep-disordered breathing (SDB) in children comprises a wide spectrum of
      symptoms ranging from primary snoring to obstructive sleep apnea (OSA). Twelve
      percent of children present primary snoring and 1-2% OSA. Polysomnography is the
      gold standard for diagnosis of SDB allowing the analysis of sleep stages,
      respiratory movements, airflow, and gas exchange. However, this test remains
      highly technical, expensive, and difficult to conduct; other simpler diagnostic
      methods are under evaluation. Recent studies highlight the frequency and
      importance of cognitive and behavioral disorders in children with SDB; both the
      age and the severity of the SDB seem to modulate in the expression of
      neurocognitive consequences. Local and systemic inflammation plays a key role in
      the physiopathology of SDB and its complications: OSA is a cardiovascular risk
      factor in childhood that could favor atheromatous complications later in life.
      Adenoidotonsillectomy is the treatment of choice, but anti-inflammatory therapies
      such as leukotriene receptor antagonists or nasal corticoids may be beneficial in
      mild SDB or in residual OSA after adenotonsillectomy. In case of failure,
      noninvasive ventilation by means of nasal continuous positive pressure will be
      necessary, aided by specialists. SDB and OSA are a public health problem,
      underlining the pivotal role of the pediatrician in preventing, diagnosing, and
      treating these frequent disorders.

PMID- 19097766
TI  - [Anorexia athletica's place in female sports athletes].
AB  - This work analyzes the links between eating disorders and intensive exercise
      training and tries to define the anorexia athletica's place in this context.
      Through a review of the literature, we examined the arguments favoring the
      hypothesis of a "princeps" disorder, which would orientate girls towards some
      sports, and the arguments, which emphasize the capacity of some sports to lead to
      the apparition of these eating disorders. The description of a clinical case
      allows the evocation of the complexity of this relationship showing that
      intensive exercise training may be a facilitatory factor as well as a limitatory
      factor of the severity of the anorexia nervosa. In this situation, it seems
      interesting to use the anorexia athletica's concept to improve coach and doctor's
      vigilance around the young female athlete. Lastly, we propose to replace the
      concept of sport by "exercise practice" where the intensity, the sport
      "centration", the weight stress became risk factors and to define populations at
      risk (adolescents, females). Based on these data, prevention actions should be
      started in populations particularly exposed.

PMID- 19097767
TI  - Association between impaired glucose tolerance and carotid atherosclerosis: a
      study in 64-year-old women and a meta-analysis.
AB  - BACKGROUND AND AIMS: Impaired glucose tolerance (IGT) is regarded as a transient
      metabolic state leading to type-2 diabetes, and is known to predict future risk
      of cardiovascular disease. This study was designed to investigate if IGT is
      associated with subclinical atherosclerosis. METHODS AND RESULTS: In a population
      based cohort of 64-year-old women, a group with IGT determined by repeated oral
      glucose tolerance tests (n=205) was compared with healthy women with normal
      glucose tolerance (NGT, n=188). Intima-media thickness (IMT) and plaques in the
      common carotid arteries (CCA) and bulbs were measured by ultrasound. The 95%
      confidence interval (CI) of the difference between the IGT and NGT groups was 
      0.03 to 0.03mm. There was no difference in carotid bulb IMT or in the occurrence,
      size, and characteristics of plaques between the IGT and NGT groups. A meta
      analysis was used to calculate summary measures of 12 reviewed studies showing a
      difference of 0.030 (95% CI 0.012-0.048) mm in carotid IMT between IGT and NGT
      groups. Heterogeneity in IMT differences between studies was shown. CONCLUSIONS:
      In our population-based cohort of 64-year-old women, IGT was not associated with
      increased occurrence of subclinical atherosclerosis. However, a meta-analysis of
      12 studies, including our current study, showed that IGT was associated with a
      small increase in the CCA IMT.

PMID- 19097768
TI  - Methods for the quantitative assessment of electrolyte disturbances in
      hyperglycaemia.
AB  - AIM: While empirical calculations are presently used, exact solutions to compute
      volume and solute changes of hyperosmolar coma (HC) can be obtained by
      subdividing the patients according to well defined clinical and laboratory
      conditions. These are represented by PNa(G), the plasma Na concentration that
      would be present if there were only glucose addition (GA), that discloses
      prevalent Na depletion when >PNa(1), prevalent water deficit when <PNa(1) (value
      measured during HC). Exact solutions are available when Na is lost as NaCl, and
      when patients are subdivided according to Posm(1) (plasma osmolality during HC)
      >, = or <Posm(0) (the normal value). When Posm(1)=Posm(0), GA must equal the loss
      of ions induced by the osmotic diuresis (2 x DeltaNa), and the math solution is
      exact. We herein report data validating these new computational methods. DATA
      SYNTHESIS: We built a mathematical model describing fluid derangements used to
      execute computer-simulated experiments of HC. The derangements were generated on
      the computer by adding, to the extra-cellular volume, different amounts of
      glucose while subtracting variable combinations of ions and solvent. The model
      yielded true solute concentrations from which our formulas computed the amounts
      lost or gained. These were identical to the true changes introduced to simulate
      the derangements (R(2)=1.00, P<0.0001) when the boundary conditions for PNa(G),
      exclusive NaCl loss and Posm(1)-Posm(0) were met. In patients with HC in whom
      these same boundary conditions were satisfied, the computations of glucose and Na
      changes with our new formulas were not significantly different from those
      estimated after correction of the derangements, considered true values
      (R(2)=0.60, P<0.05), and showed a satisfactory agreement with the clinical
      evaluation. CONCLUSIONS: Our new methods are more accurate than the traditional
      ones, as they reach a better quantitative assessment of the entity of the
      derangements, avoiding iatrogenic dysnatraemias after correction of HC.

PMID- 19097769
TI  - Postmortal diagnosis of a Dyke-Davidoff-Masson syndrome in a 75-year-old woman--
      a case report.
AB  - The Dyke-Davidoff-Masson syndrome is characterized by various symptoms related to
      hemiatrophy of the cerebrum and hypertrophy of the ipsilateral calvarium and
      paranasal sinuses. Clinical findings include hemiparesis or hemiplegia, seizures
      and/or mental retardation. The present report discusses the very unusual case of
      a late-diagnosed Dyke-Davidoff-Masson syndrome in a 75-year-old body donor who
      had suffered a left-sided stroke associated with the internal carotid artery in
      the course of tonsillitis at the age of 5.

PMID- 19097770
TI  - Antiviral activity of raoulic acid from Raoulia australis against Picornaviruses.
AB  - RNA viruses are a major source of respiratory diseases worldwide. The lack of
      effective therapeutical treatment underlines the importance of research for new
      antiviral compounds. Raoulic acid is a principal ingredient of the plant Raoulia
      australis Hook. F. Antiviral assay using cytopathic effect (CPE) reduction method
      showed that raoulic acid possessed strong antiviral activity against human
      rhinovirus 2 (HRV2) with a 50% inhibition concentration (IC(50)) value of less
      than 0.1mug/ml, human rhinovirus 3 (HRV3) with a IC(50) value of 0.19 microg/ml,
      coxsackie B3 (CB3) virus with IC(50) values of 0.33 microg/ml, coxsackie B4 (CB4)
      virus with IC(50) values of 0.40 microg/ml, and enterovirus 71 (EV71) virus with
      IC(50) values of less than 0.1 microg/ml. However, the compound did not possess
      antiviral activity against influenza A (Flu A/PR, Flu A/WS, H1N1) and B viruses
      at four concentrations ranging from 0.1 to 100 microg/ml.

PMID- 19097771
TI  - Androgenic action of Tinospora cordifolia ethanolic extract in prostate cancer
      cell line LNCaP.
AB  - AIM OF THE STUDY: Recently, Tinospora cordifolia (TC) was shown to affect
      prostate growth in rats. It is not known whether this is a direct effect of TC or
      whether it is induced by altered hormone release. To investigate the actions of
      TC on the prostate, human LNCaP cells were exposed to an ethanolic extract of TC.
      MATERIALS AND METHODS: LNCaP cells were incubated with the test substances for 48
      h. Proliferation was measured by MTT test and prostate-specific antigen (PSA)
      secretion was determined with ELISA. RESULTS: TC showed a dose-dependent
      stimulation of proliferation of LNCaP cells. Co-incubation with the anti-androgen
      flutamide (FLU) reversed the TC-induced stimulation of PSA secretion.
      CONCLUSIONS: The reference compound dihydrotestosterone (DHT) caused a
      significant increase of growth of LNCaP cells. Similarly, TC stimulated
      proliferation of these prostate cells. The anti-androgen FLU reversed the
      increase of PSA release caused by either DHT or TC. Thus, we suggest that TC may
      contain androgenic compounds, which appear to act via androgen receptor (AR).

PMID- 19097772
TI  - Observational study: Matricaria chamomilla may improve some symptoms of attention
      deficit hyperactivity disorder.
AB  - OBJECTIVE: Noradrenaline and serotonin reuptake inhibitors have been proven to be
      effective in some cases of ADHD. In this open trial, Matricaria chamomilla, a
      serotonin and noradrealine reuptake inhibitor, actually used as an
      antidepressant, has been checked for this indication. METHOD: Three 14-16-year
      old male psychiatric outpatients, diagnosed with attention-deficit disorder
      (ADHD) have been rated at baseline and while taking Matricaria chamomilla to
      determine its efficacy as a treatment for ADHD. Improvement was valuated using
      comparisons of Conners' parent ratings. RESULTS: Patients' mean scores improved
      for Conners' hyperactivity, inattention and immaturity factors. CONCLUSIONS:
      Although the sample size is very small and therefore generalization is very
      difficult, this observation indicates that Matricaria chamomilla might be a
      slightly effective treatment also for ADHD.

PMID- 19097773
TI  - Advocacy for harm reduction in China: a new era dawns.
AB  - BACKGROUND: China's initial response to drug use and HIV was largely ineffective
      but has improved with recent government endorsement of harm reduction
      interventions. This paper examines the views of senior key informants inside
      China who articulated core needs and objectives for the development of a harm
      reduction advocacy strategy. METHODS: Thirty-nine key informants (KI) were
      interviewed, representing 19 stakeholder bodies selected from the Chinese
      government public health sector, public security sector, international agencies
      such as WHO, UNODC and UNAIDS, and international non-government organisations.
      RESULTS: The concept of harm reduction is widely understood and considered valid.
      Support for harm reduction is increasing, but KIs perceived an imbalance between
      the rapid expansion of methadone maintenance treatment programs over needle and
      syringe programs and other interventions. Challenges for harm reduction
      identified by KIs included: policy inconsistencies; lack of skilled resources,
      training programs and technical capacity; poor coverage of interventions; and
      gaps in the sharing of information. KIs suggested numerous ways to strengthen the
      capacity of the government and communities to reduce drug related harm.
      DISCUSSION: Increased acceptance of harm reduction in China, particularly among
      public security, implies a new level of optimism towards addressing the HIV
      epidemic among drug users, and parallels an impressive expansion of harm
      reduction interventions. Nevertheless, scaling up a response to the ongoing dual
      epidemic of drug use and HIV remains an enormous challenge. With appropriate
      technical education and training, ongoing advocacy, and a cohesive, coordinated
      multi-sectoral effort, the capacity of the government and community to adopt,
      support and promote measures to reduce HIV and other drug related harm would be
      markedly strengthened.

PMID- 19097774
TI  - New response evaluation criteria in solid tumours: revised RECIST guideline
      (version 1.1).
AB  - BACKGROUND: Assessment of the change in tumour burden is an important feature of
      the clinical evaluation of cancer therapeutics: both tumour shrinkage (objective
      response) and disease progression are useful endpoints in clinical trials. Since
      RECIST was published in 2000, many investigators, cooperative groups, industry
      and government authorities have adopted these criteria in the assessment of
      treatment outcomes. However, a number of questions and issues have arisen which
      have led to the development of a revised RECIST guideline (version 1.1). Evidence
      for changes, summarised in separate papers in this special issue, has come from
      assessment of a large data warehouse (>6500 patients), simulation studies and
      literature reviews. HIGHLIGHTS OF REVISED RECIST 1.1: Major changes include:
      Number of lesions to be assessed: based on evidence from numerous trial databases
      merged into a data warehouse for analysis purposes, the number of lesions
      required to assess tumour burden for response determination has been reduced from
      a maximum of 10 to a maximum of five total (and from five to two per organ,
      maximum). Assessment of pathological lymph nodes is now incorporated: nodes with
      a short axis of 15 mm are considered measurable and assessable as target lesions.
      The short axis measurement should be included in the sum of lesions in
      calculation of tumour response. Nodes that shrink to <10mm short axis are
      considered normal. Confirmation of response is required for trials with response
      primary endpoint but is no longer required in randomised studies since the
      control arm serves as appropriate means of interpretation of data. Disease
      progression is clarified in several aspects: in addition to the previous
      definition of progression in target disease of 20% increase in sum, a 5mm
      absolute increase is now required as well to guard against over calling PD when
      the total sum is very small. Furthermore, there is guidance offered on what
      constitutes 'unequivocal progression' of non-measurable/non-target disease, a
      source of confusion in the original RECIST guideline. Finally, a section on
      detection of new lesions, including the interpretation of FDG-PET scan assessment
      is included. Imaging guidance: the revised RECIST includes a new imaging appendix
      with updated recommendations on the optimal anatomical assessment of lesions.
      FUTURE WORK: A key question considered by the RECIST Working Group in developing
      RECIST 1.1 was whether it was appropriate to move from anatomic unidimensional
      assessment of tumour burden to either volumetric anatomical assessment or to
      functional assessment with PET or MRI. It was concluded that, at present, there
      is not sufficient standardisation or evidence to abandon anatomical assessment of
      tumour burden. The only exception to this is in the use of FDG-PET imaging as an
      adjunct to determination of progression. As is detailed in the final paper in
      this special issue, the use of these promising newer approaches requires
      appropriate clinical validation studies.

PMID- 19097775
TI  - Recommendations for the assessment of progression in randomised cancer treatment
      trials.
AB  - Progression-free survival (PFS) is an increasingly important end-point in cancer
      drug development. However, several concerns exist regarding the use of PFS as a
      basis to compare treatments. Unlike survival, the exact time of progression is
      unknown, so progression times might be over-estimated (or under-estimated) and,
      consequently, bias may be introduced when comparing treatments. In addition, the
      assessment of progression is subject to measurement variability which may
      introduce error or bias. Ideally trials with PFS as the primary end-point should
      be randomised and, when feasible, double-blinded. All patients eligible for study
      should be evaluable for the primary end-point and thus, in general, have
      measurable disease at baseline. Appropriate definitions should be provided in the
      protocol and data collected on the case-report forms, if patients with only non
      measurable disease are eligible and/or clinical, or symptomatic progression are
      to be considered progression events for analysis. Protocol defined assessments of
      disease burden should be obtained at intervals that are symmetrical between arms.
      Independent review of imaging may be of value in randomised phase II trials and
      phase III trials as an auditing tool to detect possible bias.

PMID- 19097776
TI  - Anaerobic digestion of spent bedding from deep litter piggery housing.
AB  - This paper investigates spent litter from deep litter piggery housing as a
      potential substrate for farm-scale anaerobic digestion. Degradability and
      degradation rates were evaluated under mesophilic conditions for unused, lightly
      soiled (used by weaner/small pigs), and heavily soiled (used by finishing/large
      pigs) wheat straw, barley straw, and rice husks bedding. Apparent first order
      hydrolysis rate coefficients varied, but were comparable across all samples
      analysed (<0.1 day(-1)). Spent wheat straw was generally more degradable
      (approximately 60%) than spent barley straw, while spent barley straw was
      comparable to raw straw (40-50%), but with higher hydrolysis rates, indicating
      better accessibility. Rice husks were relatively poorly degradable (<20%), but
      degradability was improved by weathering in a pig shed. Digestion of spent barley
      and wheat straw litter was significantly faster (approximately twice the rate) at
      low (8% solids) than high (14% solids) solids loading. Rice husks degradation
      kinetics were not significantly influenced by solids concentration. Intrinsic
      methanogenic activity of heavily soiled spent wheat straw and rice husks bedding
      was initially poor, but achieved full activity after 40-60 days, indicating that
      reactor operation without external inoculum may be possible with care.

PMID- 19097777
TI  - Allosteric inhibitors of Akt1 and Akt2: discovery of [1,2,4]triazolo[3,4
      f][1,6]naphthyridines with potent and balanced activity.
AB  - A series of [1,2,4]triazolo[3,4-f][1,6]naphthyridine allosteric dual inhibitors
      of Akt1 and 2 have been developed. These compounds have been shown to have potent
      dual Akt1 and 2 cell potency. The representative compound 13 provided potent
      inhibitory activity against Akt1 and 2 in vivo in a mouse model.

PMID- 19097778
TI  - Synthesis and biological evaluation of phloridzin analogs as human concentrative
      nucleoside transporter 3 (hCNT3) inhibitors.
AB  - Nucleoside transporter inhibitors have potential therapeutic applications as
      anticancer, antiviral, cardioprotective and neuroprotective agents. Although
      quite a few potent inhibitors of the equilibrative nucleoside transporters are
      known, largely missing are the concentrative nucleoside transporter inhibitors.
      Phloridzin (3, K(i)=16.00 microM) is a known moderate inhibitor of the
      concentrative nucleoside transporters. We have synthesized and evaluated analogs
      of phloridzin at the hCNT3 nucleoside transporter. Within the series of
      synthesized analogs compound 16 (K(i)=2.88 microM), possessing a ribofuranose
      sugar unit instead of a glucopyranose as present in phloridzin, exhibited the
      highest binding affinity at the hCNT3 transporter. Phloridzin and compound 16
      have also been shown to be selective for the hCNT3 transporter as compared with
      the hENT1 transporter. Compound 16 can serve as a new lead which after further
      modifications could yield selective and potent hCNT3 inhibitors.

PMID- 19097779
TI  - Stereo-controlled synthesis of novel photoreactive gamma-secretase inhibitors.
AB  - The stereoselective synthesis of novel photoreactive gamma-secretase inhibitors 2
      and 3 has been achieved. Key steps of the strategy involve preparation of alpha-N
      Boc-epoxide 8 and formation of lactone 14 in a practical and stereo-controlled
      fashion. Compounds 2 and 3 are potent gamma-secretase inhibitors and directly
      interact with presenilin-1, a catalytic subunit of gamma-secretase.

PMID- 19097780
TI  - Identification and functional analysis of brassicicene C biosynthetic gene
      cluster in Alternaria brassicicola.
AB  - The biosynthetic gene cluster of brassicicene C was identified in Alternaria
      brassicicola strain ATCC 96836 from genome database search. In vivo and in vitro
      study clearly revealed the function of Orf8 and Orf6 as a fusicoccadiene synthase
      and methyltransferase, respectively. The understanding toward the biosynthetic
      pathway promises construction of this type of diterpene compounds with genetic
      engineering.

PMID- 19097781
TI  - 1-Oxo-3-substitute-isothiochroman-4-carboxylic acid compounds: synthesis and
      biological activities of FAS inhibition.
AB  - A new series 1-oxo-3-substitute-isothiochroman-4-carboxylic acid compounds have
      been designed and synthesized. Screening of these molecules for FAS inhibition in
      vitro has indicated that compounds 2c and 2d showed more effective FAS inhibition
      activities and higher therapeutic index than C75.

PMID- 19097782
TI  - HY253, a novel compound isolated from Aralia continentalis, induces apoptosis via
      cytochrome c-mediated intrinsic pathway in HeLa cells.
AB  - This study was aimed to elucidate the novel structure of HY253 isolated from the
      roots of Aralia continentalis and to evaluate its detailed mechanisms on
      apoptotic induction in HY253-treated HeLa cells. The structure of HY253 was
      elucidated based on the interpretation of the NMR spectra, as 7,8a-divinyl
      2,4a,4b,5,6,7,8,8a,9,9a-decahydro-1H-fluorene-2,4a,4b,9a-tetraol. The TUNEL assay
      using flow cytometer revealed an appreciable apoptotic induction in HeLa cells
      treated with 100 microM of HY253 for 48 h. This apoptotic induction is associated
      with cytochrome c release from mitochondria, via up-regulation of pro-apoptotic
      Bcl-2 proteins, such as Bax and Bak, which, in turn, resulted in the activation
      of caspase-8, -9 and -3, and the cleavage of poly(ADP-ribose) polymerase (PARP).

PMID- 19097783
TI  - 5-(2-Pyrrolidinyl)oxazolidinones and 2-(2-pyrrolidinyl)benzodioxanes: synthesis
      of all the stereoisomers and alpha4beta2 nicotinic affinity.
AB  - The four stereoisomers of 2-oxazolidinone 5-substituted with 1-methyl-2
      pyrrolidinyl (1), of 1,4-benzodioxane 2-substituted with the same residue (2) and
      of the nor-methyl analogue of this latter (2a) were synthesized as candidate
      nicotinoids. Of the 12 compounds, two N-methylated pyrrolidinyl-benzodioxane
      stereoisomers, namely those with the same relative configuration at the
      pyrrolidine stereocentre as (S)-nicotine, bind at alpha4beta2 nicotinic
      acetylcholine receptor with submicromolar affinity. Consistently with the
      biological data, docking analysis enlightens significant differences in binding
      site interactions not only between 1 and 2, but also between 2 and 2a and between
      the stereoisomers of 2 accounting for the critical role played, in the case of
      the pyrrolidinyl-benzodioxanes, by the chirality of both the stereolabile and
      stereostable stereogenic atoms, namely the protonated tertiary nitrogen and the
      two asymmetric carbons.

PMID- 19097784
TI  - Discovery of thiophene inhibitors of polo-like kinase.
AB  - The discovery and development of a series of thiophenes as potent and selective
      inhibitors of PLK is described. Identification and characterization of 2, a
      useful in vitro PLK inhibitor tool compound, is also presented.

PMID- 19097785
TI  - Chitooligosaccharides suppress the level of protein expression and
      acetylcholinesterase activity induced by Abeta25-35 in PC12 cells.
AB  - Clinical applications of acetylcholinesterase (AChE) inhibitors are widespread in
      Alzheimer's sufferers in order to activate central cholinergic system and
      alleviate cognitive deficits by inhibiting the hydrolysis of acetylcholine. In
      this study, six kinds of chitooligosaccharides (COSs) with different molecular
      weight and degree of deacetylation were examined for their inhibitory effects
      against AChE. The 90-COSs exhibited potent AChE inhibitory activities compared to
      50-COSs, while 90-MMWCOS (1000-5000 Da) in the 90-COSs showed the highest
      activity. Cell culture experiment revealed that 90-MMWCOS suppressed the level of
      AChE protein expression and AChE activity induced by Abeta(25-35) in PC12 cell
      lines.

PMID- 19097786
TI  - N,N-Dimethylsphingosine conjugates of poly-L-glutamic acid: synthesis,
      characterization, and initial biological evaluation.
AB  - Poly-L-glutamic acid (PGA) has previously been demonstrated to be an effective
      backbone for creating a hydrophilic prodrug of the established anti-tumor agent,
      paclitaxel, the active agent in Taxol; this approach has obviated the need for
      the toxic Cremophor excipient, used to enhance the solubility of paclitaxel in
      the clinical formulation. In order to form hydrophilic prodrugs of the
      hydrophobic pro-apoptotic sphingolipid, N,N-dimethylsphingosine (DMSP), PGA was
      condensed with DMSP, previously modified with coumarin to allow spectroscopic
      detection during conjugate synthesis, to yield PGA-DMSP. Conjugates with
      different loadings of DMSP were prepared and evaluated for in vitro cytotoxicity
      against two human breast adenocarcinoma cell lines. Time- and loading-dependent
      expression of cytotoxicity was observed, such that endpoints essentially
      equivalent to those observed with free-DMSP were achieved, but in a more
      protracted manner, consistent with prodrug behavior. PGA-DMSP was initially
      evaluated for toxicity in female nude mice, and administration of high net levels
      of DMSP, exceeding those achievable with free-DMSP, was well-tolerated. We
      propose that PGA-DMSP conjugates merit evaluation for anti-tumor efficacy in pre
      clinical tumor models.

PMID- 19097787
TI  - Synthesis of spiro[chroman-2,4'-piperidin]-4-one derivatives as acetyl-CoA
      carboxylase inhibitors.
AB  - Various spiro[chroman-2,4'-piperidin]-4-one derivatives (38a-m and 43a-j) have
      been designed, synthesized and evaluated for in vitro acetyl-CoA carboxylase
      (ACC) inhibitory activity. Several compounds have shown ACC inhibitory activity
      in low nanomolar range. Compound 38j reduced the respiratory quotient (RQ) in
      C57BL/6J mice indicating increase in whole body fat oxidation even in the
      presence of high carbohydrate diet. Structure-activity relationship (SAR) has
      been discussed.

PMID- 19097788
TI  - Type II NADH dehydrogenase of the respiratory chain of Plasmodium falciparum and
      its inhibitors.
AB  - Plasmodium falciparum NDH2 (pfNDH2) is a non-proton pumping, rotenone-insensitive
      alternative enzyme to the multi-subunit NADH:ubiquinone oxidoreductases (Complex
      I) of many other eukaryotes. Recombinantly expressed pfNDH2 prefers coenzyme
      CoQ(0) as an acceptor substrate, and can also use the artificial electron
      acceptors, menadione and dichlorophenol-indophenol (DCIP). Previously
      characterized NDH2 inhibitors, dibenziodolium chloride (DPI), diphenyliodonium
      chloride (IDP), and 1-hydroxy-2-dodecyl-4(1H)quinolone (HDQ) do not inhibit
      pfNDH2 activity. Here, we provide evidence that HDQ likely targets another P.
      falciparum mitochondrial enzyme, dihydroorotate dehydrogenase (pfDHOD), which is
      essential for de novo pyrimidine biosynthesis.

PMID- 19097789
TI  - Design and synthesis of vidarabine prodrugs as antiviral agents.
AB  - 5'-O-D- and L-amino acid derivatives and 5'-O-(D- and L-amino acid methyl ester
      phosphoramidate) derivatives of vidarabine (ara-A) were synthesized as vidarabine
      prodrugs. Some compounds were equi- or more potent in vitro than vidarabine
      against two pox viruses and their uptake by cultured cells was improved compared
      to the parent drug.

PMID- 19097790
TI  - Synthesis of a Streptococcus pyogenes vaccine candidate based on the M protein
      PL1 epitope.
AB  - Group A streptococcus is a Gram-positive bacteria that causes a range of
      infectious diseases. Targeting the bacteria, a new self-adjuvanting vaccine
      candidate, incorporating a carbohydrate carrier and an amino acid-based adjuvant,
      was synthesised utilising carbohydrate chemistry and solid-phase peptide
      synthesis procedures. Characterisation of the candidate was achieved using
      reverse-phase HPLC and electrospray ionisation mass spectrometry. The successful
      synthesis and characterisation of the vaccine candidate may contribute to the
      discovery of a therapeutically and clinically viable vaccine against group A
      streptococcus.

PMID- 19097791
TI  - 2-(6-Phenyl-1H-indazol-3-yl)-1H-benzo[d]imidazoles: design and synthesis of a
      potent and isoform selective PKC-zeta inhibitor.
AB  - The inhibition of PKC-zeta has been proposed to be a potential drug target for
      immune and inflammatory diseases. A series of 2-(6-phenyl-1H indazol-3-yl)-1H
      benzo[d]imidazoles with initial high crossover to CDK-2 has been optimized to
      afford potent and selective inhibitors of protein kinase c-zeta (PKC-zeta). The
      determination of the crystal structures of key inhibitor:CDK-2 complexes informed
      the design and analysis of the series. The most selective and potent analog was
      identified by variation of the aryl substituent at the 6-position of the indazole
      template to give a 4-NH(2) derivative. The analog displays good selectivity over
      other PKC isoforms (alpha, betaII, gamma, delta, epsilon, mu, theta, eta and
      iota/lambda) and CDK-2, however it displays marginal selectivity against a panel
      of other kinases (37 profiled).

PMID- 19097792
TI  - Identification of amidoheteroaryls as potent inhibitors of mutant (V600E) B-Raf
      kinase with in vivo activity.
AB  - A series of amidoheteroaryl compounds were designed and synthesized as inhibitors
      of B-Raf kinase. Several compounds from the series show excellent potency in
      biochemical, phenotypic and mode of action cellular assays. Potent examples from
      the series have also demonstrated good plasma exposure following an oral dose in
      rodents and activity against the Ras-Raf pathway in tumor bearing mice.

PMID- 19097793
TI  - The prevalence, management and outcome for patients with lower limb ulceration
      identified in a wound care survey within one English health care district.
AB  - 482 people with leg ulcers were identified among those receiving health care in
      Bradford, UK. Of these wounds 195 (40.4%) were venous leg ulcers. Typically the
      people who experienced these wounds were elderly Caucasian females however a sub
      group of younger males of Asian descent were seen to experience ulcers involving
      neuropathy. The leg ulcers were typically small in size although 33 people had
      wounds over 25 cm2 in surface area. The leg ulcers tended to persist with many
      present for at least 1 year with 4 wounds active for over 5 years. 205 people had
      experienced previous episodes of leg ulcer occurrence. Of the leg ulcers
      encountered 18.0% (n = 87) were infected and where wounds were swabbed for their
      microbial burden MRSA was identified in 8.5% of cases. Use of Doppler ultrasound
      to assess the aetiology of the wound had been performed in 66.4% of cases and
      where wounds remained undiagnosed (n = 69) only 8 had been Doppler assessed.
      While 75% of all venous leg ulcers received compression 48 people with venous leg
      ulcers did not have compression applied to their wound.

PMID- 19097794
TI  - The prevalence, management, equipment provision and outcome for patients with
      pressure ulceration identified in a wound care survey within one English health
      care district.
AB  - The prevalence of pressure ulceration within the population receiving health care
      in Bradford, UK was 0.74 people with a pressure ulcer per 1000 population (95% CI
      0.6-0.8). This prevalence includes a number of tertiary referrals and if these
      are removed the prevalence falls to 0.71 people with a pressure ulcer per 1000
      population. Of the pressure ulcers encountered 195 (53.7%) were classed as grade
      2 pressure ulcers with 80 grade 3 wounds and 40 grade 4 pressure ulcers. Forty
      eight pressure ulcers were identified as grade 1 wounds but the accuracy of this
      classification may be in doubt given that 24 apparent grade 1 pressure ulcers
      were reported to have visible wound beds with common reports of slough and
      granulation tissue. Severe pressure ulcers differed from less severe partial
      thickness wounds--grade 3 and 4 pressure ulcers tended to be larger, of longer
      duration, with greater coverage of the wound bed with necrotic tissue and less
      granulation and epithelial tissue. Wound exudate was heavier where people
      presented with severe pressure ulcers while there was a greater probability of
      wound infection (37.5% of grade 4 pressure ulcers were infected). Given these
      challenges it was perhaps unsurprising that people with severe pressure ulcers
      were more likely to have been risk assessed, to have had a critical incident form
      completed (although only 35% of grade 4 pressure ulcers were identified as having
      been reported on a critical incident form), to be provided with a powered PR
      mattress in bed and to be dressed with an antimicrobial dressing. The time to
      treat each severe pressure ulcer tended to be longer than was the treatment times
      for less severe wounds. Only 40 people with pressure ulcers (11%) as their most
      serious wound were located in hospital, suggesting that current pressure ulcer
      epidemiology and costs may be understated given their reliance on previous
      hospital based surveys of pressure ulcers. Another potential confounder of
      pressure ulcer epidemiological studies may be the number of nursing home beds in
      the surveyed population. On breaking down the Bradford audit data by postcode the
      pressure ulcer prevalence ranged between 0.13 and 1.39 people with a pressure
      ulcer per 1000 population with the higher prevalence proportions found in
      postcodes with large numbers of nursing home beds. It would appear to be prudent
      to record the number of nursing home beds within community based populations
      where pressure ulcers (and potentially other wounds) are being recorded.

PMID- 19097795
TI  - Impact of dopamine transporter single photon emission computed tomography imaging
      using I-123 ioflupane on diagnoses of patients with parkinsonian syndromes.
AB  - To assess the impact of I-123 ioflupane single photon emission computed
      tomography (SPECT) imaging on classifying patients with striatal dopaminergic
      deficits. Sixty-one patients with an initial diagnosis of parkinsonism or
      uncertain tremor disorder were screened and followed-up for one year. All
      patients were re-examined by two neurologists at our centre and were classified
      as having neurodegenerative or non-neurodegenerative disorders. Patients
      underwent I-123 ioflupane SPECT imaging. SPECT studies were blindly evaluated and
      classified as normal or abnormal (indicative of neurodegenerative disorders). The
      overall agreement of the SPECT imaging results with the initial classification
      was 65.6% (kappa=0.229, p=0.074) but was 90.2% (kappa=0.782, p<0.001) with the
      classification of the neurologists at our centre. I-123 ioflupane SPECT imaging
      is a valuable method in the evaluation of patients presenting clinically with
      uncertain parkinsonian syndromes or for whom diagnostic doubt exists.

PMID- 19097796
TI  - Osteoarthritis in patients with anterior cruciate ligament rupture: a review of
      risk factors.
AB  - The risk factors for the development of osteoarthritis (OA) in patients who have
      had an anterior cruciate ligament (ACL) rupture are reviewed. Although the
      principle arthrogenic factor is the increased anterior tibial displacement that
      is associated with the rupture, other direct and indirect factors contribute.
      Meniscal and chondral injuries can be present before, during, and develop after
      the index injury, making assessment of the relative importance of each difficult.
      Most studies concentrate on the radiological changes following ACL rupture and
      reconstruction. However the rate of significant symptomatic OA needing major
      surgical intervention is lower. This needs to be considered when advising
      patients on the management of their ruptured ACL. The long-term outcome in
      patients who are symptomatically stable following an ACL rupture is uncertain,
      although in a small cohort of elite athletes all had degenerative changes by 35
      years and eight out of 19 (42%) had undergone total knee replacement. At 20 years
      follow-up the reported risk of developing osteoarthritis is lower after ACL
      reconstruction (14%-26% with a normal medial meniscus, 37% with meniscectomy) to
      untreated ruptures (60%-100%).

PMID- 19097797
TI  - Walking shoes and laterally wedged orthoses in the clinical management of medial
      tibiofemoral osteoarthritis: a one-year prospective controlled trial.
AB  - The purpose of the study was to examine the clinical efficacy of individually
      prescribed laterally wedged orthoses and walking shoes in the treatment of medial
      knee osteoarthritis using a prospective, single-blind, block-randomized
      controlled design. Sixty-six subjects (29 males, 37 females, mean age 62.4 years,
      mean BMI 33.0 kg/m(2)) were block-randomized to a lateral wedge (treatment) or
      neutral (control) orthotic group. Both groups were issued a standardized walking
      shoe for use with the orthoses. Primary outcome measures included the pain,
      stiffness, and functional limitations subscales of the Western Ontario and
      McMaster Universities index. Secondary outcome measures included the 6-minute
      walk distance and pain change, and stair negotiation time and pain change. A
      significant interaction (p=0.039) favoring the treatment group was observed for
      pain change during the 6-minute walk. The treatment group demonstrated
      significant improvements at both 1 month (p<0.001) and 1 year (p<0.001) compared
      to baseline. The control group only demonstrated significant improvements at 1
      year (p=0.017). No other interactions were observed. Both groups were improved at
      each follow-up in the WOMAC subscales for pain (p<0.001), stiffness (p<0.001),
      and physical function (p<0.001). Both groups also improved in 6-minute walk test
      distance (p<0.001), stair negotiation test time (p=0.004), and stair negotiation
      test pain change (p<0.001). The results suggest that both neutral and laterally
      wedged orthoses may be beneficial in the management of medial knee osteoarthritis
      when used with walking shoes. However, the addition of lateral wedging was
      associated with early improvements in 6-minute walk test pain change not seen in
      the control group.

PMID- 19097798
TI  - Diaryl-dithiolanes and -isothiazoles: COX-1/COX-2 and 5-LOX-inhibitory, *OH
      scavenging and anti-adhesive activities.
AB  - Three series of non-steroidal anti-inflammatory drugs (NSAIDs) inhibiting the
      cyclooxygenase/5-lipoxygenase (COX/5-LOX) pathways as such as formation of
      hydroxyl radicals and adhesion were prepared: 4,5-diaryl isothiazoles, 4,5-diaryl
      3H-1,2-dithiole-3-thiones and 4,5-diaryl 3H-1,2-dithiole-3-ones. The aim of the
      present study was to develop substances which can intervene into the inflammatory
      processes via different mechanisms of action as multiple target non-steroidal
      anti-inflammatory drugs (MTNSAIDs) with increased anti-inflammatory potential.
      The current lead 11a was evaluated in COX-1/2, 5-LOX and (*)OH scavenging in
      vitro assays and in a static adhesion assay where it proved to inhibit adhesion.
      Moreover, 11a treatment attenuated expression of macrophage adhesion molecule-1
      (Mac-1) on extravasated polymorphonuclear leukocytes (PMNs) which indicates that
      the activation was reduced. The assays used are predictive for the in vivo
      efficacy of test compounds as shown for 11a in a peritonitis model of acute
      inflammation in mice. Thus, the novel 5-LOX/COX and (*)OH inhibitor 11a possesses
      anti-inflammatory activity that, in addition to COX/5-LOX inhibition, implicates
      effects on leukocyte-endothelial interactions.

PMID- 19097799
TI  - Discovery of a potent and selective inhibitor for human carbonyl reductase 1 from
      propionate scanning applied to the macrolide zearalenone.
AB  - In order to extend the chemical diversity available for organic polyketide
      synthesis, the concept of propionate scanning was developed. We observed that
      naturally occurring polyketides frequently comprise not only acetate, but also
      some propionate as building blocks. Therefore our approach consists of a
      systematic replacement of some of the acetate building blocks during synthesis by
      propionate moieties, resulting in additional methyl groups that may give rise to
      different properties of the polyketides. Here we present the results of a first
      'proof of concept' study where a novel zearalenone analogue 5 was prepared that
      comprises an additional methyl group at C5'. Key steps in the synthesis of 5
      include a Marshall-Tamaru reaction, a Suzuki cross-coupling reaction, and a
      Mitsunobu lactonization. Compared to the parent zearalenone (1), analogue 5
      showed reduced binding to a panel of human protein kinases and no binding to
      human Hsp90. On the other hand, however, 5 turned out to be a potent (IC(50)=210
      nM) inhibitor of human carbonyl reductase 1 (CBR1).

PMID- 19097800
TI  - Interaction between double helix DNA fragments and a new topopyrone acting as
      human topoisomerase I poison.
AB  - A water soluble derivative (2) of topopyrones was selected for NMR studies
      directed to elucidate the mode of binding with specific oligonucleotides.
      Topopyrone 2 can intercalate into the CG base pairs, but the residence time into
      the double helix is very short and a fast chemical exchange averaging occurs at
      room temperature between the free and bound species. The equilibria involved
      become slow below room temperature, thus allowing to measure a mean lifetime of
      the complex of ca. 7 ms at 15 degrees C. Structural models of the complex with
      d(CGTACG)(2) were developed on the basis of DOSY, 2D NOESY and (31)P NMR
      experiments. Topopyrone 2 presents a strong tendency to self-associate. In the
      presence of oligonucleotide a certain number of ligand molecules are found to
      externally stack to the double-helix, in addition to a small fraction of the same
      ligand intercalated. The external binding to the ionic surface of the
      phosphoribose chains may thus represents the first step of the intercalation
      process.

PMID- 19097801
TI  - Identification of PaCOL1 and PaCOL2, two CONSTANS-like genes showing decreased
      transcript levels preceding short day induced growth cessation in Norway spruce.
AB  - In woody plants of the temperate zone short photoperiod (SD) leads to growth
      cessation. In angiosperms CONSTANS (CO) or CO-like genes play an important role
      in the photoperiodic control of flowering, tuberisation and shoot growth. To
      investigate the role of CO-like genes in photoperiodic control of shoot
      elongation in gymnosperms, PaCOL1 and PaCOL2 were isolated from Norway spruce.
      PaCOL1 encodes a 3.9kb gene with a predicted protein of 444 amino acids. PaCOL2
      encodes a 1.2kb gene with a predicted protein of 385 amino acids. Both genes
      consist of two exons and have conserved domains found in other CO-like genes; two
      zinc finger domains, a CCT and a COOH domain. PaCOL1 and PaCOL2 fall into the
      group 1c clade of the CO-like genes, and are thus distinct from Arabidopsis CO
      that belongs to group 1a. Transcript levels of both PaCOL-genes appear to be
      light regulated, an increasing trend was observed upon transition from darkness
      to light, and a decreasing trend during darkness. The increasing trend at dawn
      was observed both in needles and shoot tips, whereas the decreasing trend in
      darkness was most prominent in shoot tips, and limited to the late part of the
      dark period in needles. The transcript levels of both genes decreased
      significantly in both tissues under SD prior to growth cessation and bud
      formation. This might suggest an involvement in photoperiodic control of shoot
      elongation or might be a consequence of regulation by light.

PMID- 19097802
TI  - Photodynamic therapy with aluminum-chloro-phthalocyanine induces necrosis and
      vascular damage in mice tongue tumors.
AB  - In this paper we describe the efficacy of the liposomal-AlClPc (aluminum-chloro
      phthalocyanine) formulation in PDT study against Ehrlich tumor cells
      proliferation in immunocompetent swiss mice tongue. Experiments were conduced in
      sixteen tumor induced mice that were divided in three control groups: (1) tumor
      without treatment; (2) tumor with 100J/cm(2) laser (670nm) irradiation; and (3)
      tumor with AlClPc peritumoral injection; and a PDT experimental group when tumors
      received AlClPc injection followed by tumor irradiation. Control groups present
      similar macroscopically and histological patterns after treatments, while PDT
      treatment induced 90% of Ehrlich tumor necrosis after 24h of one single
      application, showing the efficacy of liposome-AlClPc (aluminum-chloro
      phthalocyanine) mediated PDT on the treatment of oral cancer.

PMID- 19097803
TI  - Protective effect of melatonin on photo-damage to lysozyme.
AB  - The behavior of melatonin in the riboflavin-sensitized photo-oxidation of
      lysozyme was monitored. Melatonin was found to prevent aggregation of protein and
      the decrease of enzyme activity induced by photo-oxidation. Electron spin
      resonance experiments showed that photo-oxidation of lysozyme in the presence of
      riboflavin resulted in formation of protein radicals, and melatonin was highly
      effective in reducing the formation of protein radicals. Direct evidence of
      melatonin's ability for quenching the triplet state of riboflavin and singlet
      oxygen was presented. A mechanism of the protective effect of melatonin on photo
      oxidation of protein was proposed and the physiological relevance was discussed.

PMID- 19097804
TI  - Endurance training induces depot-specific changes in IL-10/TNF-alpha ratio in rat
      adipose tissue.
AB  - White adipose tissue (WAT) is the source of pro- and anti-inflammatory cytokines
      and recently, it has been recognized as an important source of interleukin 10 (IL
      10). Acute physical exercise is known to induce an anti-inflammatory cytokine
      profile, however, the effect of chronic physical exercise on the production of IL
      10 by WAT has never been examined. We assessed IL-10 and TNF-alpha concentration
      in WAT of rats engaged in endurance training. Animals were randomly assigned to
      either a sedentary control group (S, n=7) or an endurance trained group (T, n=8).
      Trained rats ran on a treadmill 5 days/wk for 8 wk (55-65% VO(2max)). Detection
      of IL-10 and TNF-alpha protein and mRNA expression, as well as the gene
      expression of PPAR-gamma, and immunocytochemistry to detect mononuclear
      phagocytes were carried out. A reduction in absolute retroperitoneal adipose
      tissue (RPAT) weight in T (44%; p<0.01), when compared with S was observed. IL-10
      concentration was increased (1.5-fold, p<0.05), to a higher extent than that of
      TNF-alpha (66%, p<0.05) in the mesenteric adipose tissue (MEAT) of the trained
      group, while no change related to training was observed in RPAT. In MEAT, IL
      10/TNF-alpha ratio was increased in T, when compared with S (30%; p<0.05). PPAR
      gamma gene expression was increased in T (1.1-fold; p<0.01), when compared with S
      in the same adipose depot. No monocyte infiltration was found. In conclusion,
      exercise training induced increased IL-10 expression in the mesenteric depot,
      resulting in a modified IL-10/TNF-alpha ratio. We also conclude that WAT presents
      a depot-specific response to endurance training regarding the studied aspects.

PMID- 19097805
TI  - Safety and feasibility of outpatient transcatheter hepatic arterial embolization
      for hepatocellular carcinoma.
AB  - PURPOSE: To evaluate the feasibility and safety of performing image-guided bland
      embolization and chemoembolization as an outpatient-based procedure in selected
      patients with hepatocellular carcinoma (HCC). MATERIALS AND METHODS: This is a
      retrospective review of the authors' experience with outpatient embolization and
      chemoembolization from January 2005 to June 2006. Patients with nonresectable HCC
      not eligible for liver transplantation were enrolled. Patients with Child-Pugh
      class A and early class B liver disease were treated by using the outpatient
      protocol, patients with Child-Pugh class C and late class B liver disease and
      those with elevated bilirubin or creatinine levels were excluded and treated as
      inpatients or denied embolization therapy. One hundred thirty-three bland
      embolizations or chemoembolizations were performed in 77 patients on an
      outpatient basis during the study period. RESULTS: Patients were discharged home
      on the same day after 131 of the 133 procedures (99%; 95% confidence interval
      [CI]: +/-2%), in two cases (2%, 95% CI: +/-2%), patients were admitted the day of
      the procedure. In two of the 131 cases (2%, 95% CI: +/-2%), patients discharged
      home returned to the emergency department 1-6 days after the procedure. One
      hundred twenty-nine of the 133 cases (97%, 95% CI: +/-3%) were successfully
      treated by using the outpatient embolization or chemoembolization protocol, with
      subsequent hospitalization needed in only four of 133 cases (3%, 95% CI: +/-3%).
      CONCLUSIONS: Image-guided hepatic bland embolization and chemoembolization
      performed with an outpatient protocol in carefully selected patients with HCC
      with aggressive follow-up is safe, with relatively few complications and few
      requirements for admission or revisitation to the emergency department.

PMID- 19097806
TI  - Endovascular treatment of venous graft stenosis in the inferior vena cava and the
      left hepatic vein after complex liver tumor resection.
AB  - Endovascular treatment has been reported for a variety of conditions that result
      in venous obstruction in the iliocaval territory. The present report describes a
      patient who underwent a complex resection of a tumor that infiltrated the
      retrohepatic segment of the inferior vena cava (IVC), necessitating replacement
      of the IVC with a polytetrafluoroethylene (PTFE) graft. Postoperatively,
      symptomatic venous obstruction occurred in the graft and the left hepatic vein.
      Treatment required stent placement bridging native veins and the graft. The
      patient underwent placement of a self-expanding stent within the IVC and the PTFE
      graft with treatment of the hepatic vein stenosis via jugular vein access.

PMID- 19097807
TI  - Secondary infections of thoracic and abdominal aortic endografts.
AB  - PURPOSE: To review several cases of stent-graft infection with respective
      outcomes to identify clinical presentations and responses to treatment options.
      MATERIALS AND METHODS: The authors performed a single-center retrospective review
      of all secondary endograft infections from January 2000 to June 2007. Infections
      were identified from an institutional database containing all abdominal and
      thoracic endovascular aneurysm repairs (EVAR and TEVAR) performed at the treating
      hospital. RESULTS: From January 2000 to June 2007, 389 EVAR and 105 TEVAR were
      performed at the treating hospital. Ten endograft infections were identified
      (five EVAR and five TEVAR). Four infections occurred in grafts placed at outside
      institutions and six in grafts placed in-house. The in-house prevalence of EVAR
      and TEVAR infection is 0.26% and 4.77%, respectively. None were placed for a
      presumed pre-existing mycotic aneurysm. The mean time from the index procedure to
      the diagnosis of infection was 243.6 days +/- 74.5. Two patients who underwent
      EVAR presented with a contained rupture, and the remaining eight patients
      presented with constitutional symptoms and/or abscess formation on imaging
      studies. Microbiology cultures revealed Propionibacterium species (n = 3),
      Staphylcoccus species (n = 3), Streptococcus species (n = 2), and Enterobacter
      cloacae (n = 1). All EVAR patients underwent removal of the infected endograft
      and reconstruction with extraanatomic bypass (n = 3) or in situ homograft
      placement (n = 2). During a mean follow-up of more than 1 year, there were no
      recognized complications or recurrence of infection. Only one of the five TEVAR
      patients underwent removal and interposition grafting with an antibiotic
      impregnated Dacron graft. The remaining four patients were medically managed--one
      patient survived and was placed in hospice care, two died of mycotic aneurysm
      rupture, and one died from multiorgan system failure secondary to sepsis.
      CONCLUSIONS: Graft-related septic complications following EVAR or TEVAR are rare
      but associated with significant mortality. Several surgical treatment options are
      available, each potentially equally successful. The effect of prophylactic
      antibiotic use during subsequent invasive procedures must be solidified.

PMID- 19097808
TI  - Endovascular diagnosis and intervention in patients with isolated hyperammonemia,
      with or without ascites, after liver transplantation.
AB  - Hyperammonemia with or without ascites with normal synthetic liver functions
      after liver transplantation might indicate the presence of anastomotic stenosis
      of the portal or hepatic vein or the existence of a patent portosystemic shunt.
      The authors describe six patients, three children after split-liver
      transplantation and three adults after cadaver liver transplantation, who
      presented with hyperammonemia. Three patients had ascites. All lesions were
      successfully treated percutaneously; stents were placed in patients with
      anastomotic stenoses and coil embolization was performed in patients with patent
      portosystemic shunts--with either transhepatic or transjugular approaches
      according to the site of the abnormality. Ammonia levels returned to normal, and
      ascites had regressed completely for at least 3 months.

PMID- 19097809
TI  - Improving quality and patient safety by minimizing unnecessary variation.
AB  - Quality and safety in health care have proven difficult to precisely define and
      measure. In other fields, quality is defined as the absence of unnecessary
      variation and process improvement efforts are gauged by their ability to reduce
      variation. This article explores how this definition can be applied to various
      attributes of image-guided procedures.

PMID- 19097810
TI  - Radiofrequency ablation combined with chemoembolization for the treatment of
      hepatocellular carcinomas larger than 5 cm.
AB  - PURPOSE: To evaluate survival, recurrence-free survival, technical success,
      technique effectiveness, and safety of radiofrequency (RF) ablation combined with
      chemoembolization in patients with hepatocellular carcinomas (HCCs) larger than 5
      cm. MATERIALS AND METHODS: Patients with Child-Pugh class A or B cirrhosis and
      three or fewer HCCs with a maximum tumor diameter of 5.1-10 cm were included.
      Twenty patients with 32 HCCs were included. There were 16 men and four women with
      mean age of 69 years +/- 7.4 (range, 46-79 years).The maximum mean tumor diameter
      was 6.2 cm (range, 5.1-9.5 cm). RF ablation was performed under computed
      tomographic (CT) fluoroscopic guidance 1-2 weeks after chemoembolization. The
      primary endpoint of this study was survival. RESULTS: RF electrodes were placed
      in the planned sites, and RF ablation was completed with a planned protocol
      (technical success rate, 100%). Tumor enhancement was eradicated in all patients
      after 32 RF sessions. The primary and secondary technique effectiveness rates
      were 40% and 100%, respectively. There were two major complications in the 32 RF
      sessions (6%)--hepatic abscess and diaphragm perforation. Local tumor progression
      developed in five of the 20 patients (25%) during the mean follow-up of 30
      months. The overall and recurrence-free survival rates were, respectively, 100%
      and 74% at 1 year, 62% and 28% at 3 years, and 41% and 14% at 5 years. The serum
      bilirubin level of 1.0 mg/dL (17.1 micromol/L) or less was a significantly better
      prognostic factor in the univariate analysis. CONCLUSIONS: This combination
      therapy may enhance survival in patients with HCCs larger than 5 cm.

PMID- 19097811
TI  - Are patients with hematuria appropriately referred to Urology? A multi
      institutional questionnaire based survey.
AB  - INTRODUCTION: Hematuria is a common finding that may be a sign of serious
      underlying urologic disease. Thus, the AUA guidelines (written in conjunction
      with the American Academy of Family Practice) recommend urologic evaluation for
      patients with both microscopic and gross hematuria. We sought to evaluate
      practice patterns of the evaluation of hematuria by primary care physicians
      (PCPs) in two locations in the United States. METHODS: Anonymous questionnaires
      regarding use of urinalysis (UA) and evaluation of hematuria were mailed to 586
      PCPs in Miami, Florida and 1,915 in Dallas, Texas. Surveys were mailed to
      physicians who identified themselves as practitioners of internal medicine,
      family practice, primary care, or obstetrics and gynecology. RESULTS: Surveys
      were completed by 788 PCPs including 270 (46%) and 518 (26%) PCPs in Miami and
      Dallas, respectively. Screening UAs were obtained on all patients by 77% and 64%,
      of physicians in Miami and Dallas, respectively. In both Miami and Dallas, only
      36% of PCPs reported referring patients with microscopic hematuria to an
      urologist. In patients with gross hematuria, referral rates were 77% and 69% in
      Miami and Dallas, respectively. CONCLUSIONS: While many PCPs use UA in many of
      their patients routinely, few PCPs automatically refer their patients with
      microscopic hematuria to urology and not all patients with gross hematuria are
      referred. Further investigations regarding why and when patients are referred to
      urology is warranted. Increasing awareness of the complete and timely evaluation
      of hematuria may be beneficial in preventing a delay in bladder cancer.

PMID- 19097812
TI  - Complications of open primary and post-chemotherapy retroperitoneal lymph node
      dissection for testicular cancer.
AB  - OBJECTIVE: Treatment decisions regarding the use of retroperitoneal lymph node
      dissection (RPLND) for low-stage and advanced testicular cancer may be influenced
      by the morbidity of the procedure. We sought to compare the complication profile
      of primary (P-) and post-chemotherapy (PC-) RPLND using a standardized
      complication grading scale. MATERIALS AND METHODS: A retrospective analysis was
      conducted of 112 and 96 patients who underwent P-RPLND and PC-RPLND,
      respectively, between 1982 and 2007 for perioperative outcomes and late
      complications. Postoperative complications were graded using a 5-tiered scale
      based on the severity and/or level of intervention required for resolution.
      RESULTS: P-RPLND patients had rates of 5%, 24%, and 7% for intraoperative,
      postoperative, and late complications, respectively. For PC-RPLND, these rates
      were 12%, 32%, and 7%, respectively (P = 0.11, 0.19, and 1, respectively). Major
      postoperative complications (grades III-V) were observed in 3 (3%) P-RPLND and 8
      (8%) PC-RPLND patients (P = 0.15), including 1 fatal pulmonary embolus in a PC
      RPLND patient. Ileus accounted for 63% and 45% of postoperative complications of
      P-RPLND and PC-RPLND, respectively. PC-RPLND was associated with significantly
      greater operative times, blood loss, and transfusion rates (P < 0.001). Compared
      with PC-RPLND after first-line chemotherapy for advanced NSGCT, there were no
      significant differences in perioperative outcomes for PC-RPLND performed in other
      settings. CONCLUSIONS: P-RPLND and PC-RPLND are associated with low rates of
      serious short- and long-term complications and negligible mortality, without
      significant differences between the 2 procedures. The safe morbidity profile of
      RPLND performed by fellowship-trained urologic oncologists should be considered
      during treatment decision-making for low-stage and advanced testicular cancer.

PMID- 19097813
TI  - Acute aortic dissection: perspectives from the International Registry of Acute
      Aortic Dissection (IRAD).
AB  - Acute aortic dissection is a rare but deadly disease first described over 200
      years ago by the physician to the late King George II on necropsy. Over the
      ensuing 2 centuries, the understanding of the pathophysiology, presentation,
      diagnosis, treatment and follow-up has matured. In an effort to understand the
      contemporary treatment of this disease, the International Registry of Acute
      Aortic Dissection (IRAD) has enrolled over 2000 patients over the past 12 years.
      In this article we summarize the key lessons learned from this multi-national
      registry of patients presenting with acute aortic dissection.

PMID- 19097814
TI  - A systematic review of the effects of acupuncture in treating insomnia.
AB  - To examine the extent to which research supports the use of acupuncture in
      treating insomnia, a systematic review was conducted that included not only
      clinical trials, but also case series in both English and Chinese literature.
      Thirty studies were included in the review, 93% of which showed positive
      treatment effects of acupuncture in improving various aspects of sleep. Although
      acupuncture has been demonstrated to be safe and holds great potential to be an
      effective treatment modality for insomnia, the evidence is limited by the quality
      of these studies and mixed results from those with sham (or unreal treatment)
      controls. Of the thirty studies, twelve were clinical trials with only three
      double-blinded. Only five used sham controls, and of these, four showed
      statistically significant differences favoring real treatments; however, none
      evaluated the adequacy of sham assignment. Three studies used actigraphy or
      polysomnography as objective outcome measures. The considerable heterogeneity of
      acupuncture techniques and acupoint selections among all studies made the results
      difficult to compare and integrate. High-quality randomized clinical trials of
      acupuncture in treating insomnia, with proper sham and blinding procedures will
      be required in the future. This review highlights aspects of acupuncture
      treatments important to guide future research and clinical practice.

PMID- 19097815
TI  - Di-tri-octahedral smectite for the prevention of post-operative diarrhea in
      equids with surgical disease of the large intestine: results of a randomized
      clinical trial.
AB  - The aim of this study was to evaluate the effects of a commercially available di
      tri-octahedral (DTO) smectite product on clinical signs and prevalence of post
      operative diarrhea in horses with colic associated with disease of the large
      intestine. Sixty-seven horses with surgical disease of the large intestine were
      randomly assigned to be treated with DTO smectite (n=37; 0.5 kg via nasogastric
      intubation every 24 h for 3 days post-operatively) or a placebo (n=30). The
      effect of treatment on fecal scores and clinical and hematological parameters,
      including heart rate, mucous membrane color, temperature, total white blood cell
      count, total neutrophil count and total plasma protein values, were determined.
      Horses treated with DTO smectite had a significant reduction in the prevalence of
      post-operative diarrhea (10.8%), compared with controls (41.4%). A significant
      improvement in mucous membrane color was observed 72 h post-operatively in horses
      receiving treatment, compared with placebo. Administration of DTO smectite to
      colic patients with disease of the large intestine reduced the occurrence of
      diarrhea in the early post-operative period.

PMID- 19097816
TI  - Inner hydrogen atom transfer in benzo-fused low symmetrical metal-free
      tetraazaporphyrin and phthalocyanine analogues: density functional theory
      studies.
AB  - Density functional theory (DFT) calculations were carried out to study the inner
      hydrogen atom transfer in low symmetrical metal-free tetrapyrrole analogues
      ranging from tetraazaporphyrin H(2)TAP (A(0)B(0)C(0)D(0)) to naphthalocyanine
      H(2)Nc (A(2)B(2)C(2)D(2)) via phthalocyanine H(2)Pc (A(1)B(1)C(1)D(1)). All the
      transition paths of sixteen different compounds (A(0)B(0)C(0)D(0)
      A(2)B(2)C(2)D(2) and A(0)B(0)C(m)D(n), m <or= n <or= 3) are fully optimized at
      the B3LYP/6-31G(d) level and vibration analyses have been conducted to verify the
      optimized structures. It is revealed that the number and position of fused
      benzene rings onto the TAP skeleton have significant effect on the potential
      energy barrier of the inner hydrogen atom transfer. Introducing fused benzene
      rings onto the hydrogen-releasing pyrrole rings can increase the transitivity of
      inner hydrogen atom and thus lower the transfer barrier of this inner hydrogen
      atom while fusing benzene rings onto the hydrogen-accepting pyrrole rings will
      increase the hydrogen transfer barrier to this pyrrole ring. The transient cis
      isomer intermediate with hydrogen atoms joined to the two adjacent pyrrole rings
      with less fused benzene rings is much stable than the others. It is also found
      that the benzene rings fused directly onto pyrrole rings have more effect on the
      inner hydrogen atom transfer than the outer benzene rings fused onto the
      periphery of isoindole rings. The present work, representing the first effort
      towards systematically understanding the effect of ring enlargement through
      asymmetrical peripheral fusion of benzene ring(s) onto the TAP skeleton on the
      inner hydrogen transfer of tetrapyrrole derivatives, will be helpful in
      clarifying the N-H tautomerization phenomenon and detecting the cis-porphyrin
      isomer in bio-systems.

PMID- 19097817
TI  - Follow-up examinations after medical treatment of pyometra in cats with the
      progesterone-antagonist aglepristone.
AB  - The aim of this study was to determine the therapeutic success of the medical
      treatment of pyometra with the antigestagen aglepristone and to document the
      recurrence rate in relation to the time interval after treatment with
      antigestagens in cats. Ten cats, 2-13 years of age and nulliparous were used in
      the study. The cats were treated with aglepristone at a dose of 10mg/kg body
      weight subcutaneously on days 1, 2, 7 and 14 (if not cured). In addition,
      trimethoprim/sulphadoxine was also administered at a dose of 15mg/kg body weight
      subcutaneously once a day for 7 days. Nine out of the 10 cats responded well to
      treatment. No recurrence was observed in a follow-up period of 2 years. No side
      effects were observed. The data suggest that aglepristone treatment is a
      promising approach for the medical treatment of pyometra in cats.

PMID- 19097818
TI  - Screening for diabetic retinopathy in a rural French population with a mobile non
      mydriatic camera.
AB  - AIM: The aim of this study was to evaluate the yield of diabetic retinopathy (DR)
      screening in a rural population using a mobile non-mydriatic camera. METHODS: The
      72 least medicalized areas of Burgundy were the target areas. An orthoptist took
      fundus photographs using a Topcon TRC-NW6S non-mydriatic camera (four fields:
      posterior pole; nasal; temporal; and upper). Interpretations were done in the
      Department of Ophthalmology according to the classification of the French
      Language Association for the Study of Diabetes and Metabolic Diseases (Alfediam).
      RESULTS: Between 2004 and 2006, 1974 diabetics were screened-676 the first year,
      and 1298 in the second. The rate of non-interpretable photographs was 13%. Of the
      1974 screened patients, there were 103 cases of DR (5.2%), comprising 70 mild non
      proliferative DR (68%), 21 moderate non-proliferative DR (20.4%) and 12 severe
      non-proliferative DR (11.6%). The mean age of the patients with a DR was 66.7+/
      10.9 years, with a mean duration of diabetes of 16.5+/-9.8 years. Only 35 (34%)
      patients were aware of their HbA(1c), which had a mean value of 7.8% and 19 had
      visited an ophthalmologist in the year before screening (18.4%). After the
      initial screening, 90,5% of the patients consulted an ophthalmologist as
      recommended. CONCLUSION: Screening improved the quality of the ocular follow-up
      in diabetics in this rural area. However, improvements in management are needed
      to lower the cost of such a programme.

PMID- 19097820
TI  - The molecular structure and vibrational spectra of N-(2,2-diphenylacetyl)-N'
      (naphthalen-1yl)-thiourea by Hartree-Fock and density functional methods.
AB  - N-(2,2-Diphenylacetyl)-N'-(naphthalen-1yl)-thiourea (PANT) has been synthesized
      and characterized by elemental analysis, IR spectroscopy and (1)H NMR
      spectroscopy. The crystal and molecular structure of the title compound has been
      determined from single crystal X-ray diffraction data. It crystallizes in the
      triclinic space group P-1, Z=2 with a=10.284(2)A, b=10.790(2)A, c=11.305(2)A,
      alpha=64.92(3) degrees , beta=89.88(3) degrees , gamma=62.99(3) degrees ,
      V=983.7(3)A(3) and D(calc)=1.339Mg/m(3). The molecular structure, vibrational
      frequencies and infrared intensities of PANT were calculated by the Hartree-Fock
      and density functional theory methods (BLYP and B3LYP) using the 6-31G* basis
      set. The calculated geometric parameters were compared to the corresponding X-ray
      structure of the title compound. We obtained 22 stable conformers for the title
      compound; however Conformer 1 is approximately 9.53kcal/mol more stable than
      Conformer 22. The comparison of the theoretical and experimental geometry of the
      title compound shows that the X-ray parameters fairly well reproduce the geometry
      of Conformer 17. The harmonic vibrations computed for this compound by the
      B3LYP/6-31G* method are in good agreement with the observed IR spectral data.
      Theoretical vibrational spectra of the title compound were interpreted by means
      of PEDs using the VEDA 4 program. A general better performance of the
      investigated methods was calculated by PAVF 1.0 program.

PMID- 19097821
TI  - Continuous hemodiafiltration in the treatment of reactive hemophagocytic syndrome
      refractory to medical therapy.
AB  - Reactive (or secondary) hemophagocytic syndrome (RHS) is a potentially lethal
      condition and characterized by hypercytokinemia. Immune modulating drugs
      sometimes fail to achieve satisfactory control. Therefore we investigate the
      efficacy of continuous hemodiafiltration using a polymethyl methacrylate membrane
      hemofilter (PMMA-CHDF) for cytokine removal in patients with RHS. Eight
      consecutive patients who admitted to our ICU with RHS complicating organ failures
      and refractory to medical therapy were initiated intensive care including PMMA
      CHDF. Although remission was achieved in six patients, remaining two patients
      died of exacerbation of underlying diseases. Changes in blood levels of tumor
      necrosis factor alpha (TNF-alpha) and interleukin 6 (IL-6) as indices of cytokine
      network activation, and serum ferritin level as an index of severity of RHS were
      investigated during PMMA-CHDF. PMMA-CHDF performed for 3 days significantly
      reduced blood TNF-alpha level (183+/-159 pg/ml to 84+/-98 pg/ml, p<0.05) and also
      blood IL-6 level (1113+/-903 pg/ml to 402+/-411 pg/ml, p<0.01). Furthermore,
      serum ferritin level was significantly decreased 3 days after initiation of PMMA
      CHDF (52390+/-65168 ng/ml to 4136+/-2932 ng/ml, p<0.05) although it tended to
      increase before initiation of PMMA-CHDF. No PMMA-CHDF-related adverse events were
      observed in any of the patients. PMMA-CHDF was effective to remove cytokine and
      improved disease severity. Thus, PMMA-CHDF may be an adjunctive treatment in RHS
      refractory to medical therapy.

PMID- 19097822
TI  - Multiple circumferential urethrocutaneous fistulae: a rare complication of
      circumcision.
AB  - The complications of circumcision are wide ranging, urethrocutaneous fistula
      being one of the less common. This complication affects the ventral aspect of the
      penis and is usually solitary. We present a rare case of multiple fistulae after
      circumcision with two fistulae over the dorsal aspect of the penis. A 6-year-old
      male child presented with passage of urine from four openings. He had undergone a
      ritual circumcision by non-medical personnel. The urinary steam from the normally
      situated meatus was thin. The patient was passing urine mainly from the two
      openings which were situated on the dorsolateral aspect of the penis. On physical
      examination, there were three fistulous openings circumferentially over the
      corona, two over the dorsal aspect and one over the ventral aspect. During
      surgery a loop of linen thread was found eroding the urethra along with a
      constriction ring at the corona causing a 'tourniquet-like' effect. All three
      external urethral openings were combining to form a single urethral opening at
      the corona which itself occupied more than half of the urethral circumference.
      Resection of fistulae with anastomosis of the urethra was carried out.
      Postoperatively, the patient passed urine from a normal meatus with a good
      stream.

PMID- 19097823
TI  - Conservative treatment of phimosis with fluticasone proprionate 0.05%: a clinical
      study in 1185 boys.
AB  - OBJECTIVE: Circumcision has been the traditional method of choice in the
      treatment of boys with phimosis. Recently, several published studies worldwide
      have focused their interest on more conservative approaches in management of this
      condition. These studies advocate the use of topical steroids in the phimotic
      foreskin. We aimed to investigate the efficacy and safety of a medium potency
      corticosteroid in boys with different types of prepuce retractabilty. PATIENTS
      AND METHODS: A prospective study was performed involving boys referred to our
      hospital for possible phimosis between January 2004 and February 2008. All were
      treated initially with fluticasone proprionate 0.05% for a period of 4-8 weeks.
      Patients were reassessed after 6 months of follow up. RESULTS: A total of 1185
      boys with a diagnosis of phimosis were treated with fluticasone proprionate
      0.05%. Successful results were achieved in 1079 (91.1%) patients including boys
      with mild balanitis xerotica obliterans. No side effects were noticed.
      CONCLUSION: Our results show that fluticasone proprionate 0.05%, a mild potent
      corticosteroid, is effective and safe in the treatment of boys with different
      types of phimosis.

PMID- 19097824
TI  - T-bet, pSTAT1 and pSTAT3 expression in peripheral blood mononuclear cells during
      pregnancy correlates with post-partum activation of multiple sclerosis.
AB  - In pregnant women affected by multiple sclerosis (MS) we observed increased
      percentages of CD4(+)CD25(+)Foxp3(+) T regulatory cells at the 1st and the 2nd
      trimester of gestation that was associated with a decreased T-bet expression in
      CD4(+) T cells. In women showing clinical relapse and/or new lesions at MRI after
      delivery we found, a higher expression of T-bet, pSTAT1 and pSTAT3 in CD4(+),
      CD8(+) T cells and CD14(+) cells, associated with an increase of IFNgamma and
      IL17 production by PBMC at the 3rd trimester of gestation and after delivery. Our
      data suggest that the expansion of circulating CD4(+)CD25(+)Foxp3(+) regulatory T
      cells and the lower expression of T-bet in CD4(+) T cells may account for the
      decreased MS activity during pregnancy. The expression of T-bet, pSTAT1 and
      pSTAT3 in peripheral blood CD4(+) and CD8(+) T cells and monocytes could be
      useful to identify MS patients who will develop a relapse after delivery.

PMID- 19097825
TI  - Severe combined immunodeficiency (SCID) and attention deficit hyperactivity
      disorder (ADHD) associated with a Coronin-1A mutation and a chromosome 16p11.2
      deletion.
AB  - Defects causing severe combined immunodeficiency (SCID) have been reported in
      pathways mediating antigen receptor rearrangement, antigen receptor and cytokine
      signaling, and purine metabolism. Recognizing that the actin regulator Coronin-1A
      is essential for development of a normal peripheral T cell compartment in mouse
      models, we identified absence of Coronin-1A in a girl with T-B+NK+ SCID who
      suffered recurrent infections including severe post-vaccination varicella at age
      13 months. Murine Coronin-1A is essential for the release of T cells from the
      thymus, consistent with the paradoxically detectable thymus in our patient.
      Molecular analysis revealed a 2 bp deletion in the paternal CORO1A coding
      sequence paired with a 600 kb de novo deletion encompassing CORO1A on the
      maternal allele. This genomic region at 16p11.2 is subject to recurrent copy
      number variations associated with autism spectrum disorders, including attention
      deficit and hyperactivity, present in our patient. This case highlights the first
      link between actin cytoskeleton regulation and SCID.

PMID- 19097826
TI  - Autoimmune autonomic ganglionopathy with Sjogren's syndrome: significance of
      ganglionic acetylcholine receptor antibody and therapeutic approach.
AB  - Autoimmune autonomic ganglionopathy (AAG) is a disorder defined by antibodies to
      the nicotinic acetylcholine receptor of the autonomic ganglia. We report two
      patients with chronically progressing dysautonomia with Sjogren's syndrome (SS).
      The first case showed elevated titer of ganglionic acetylcholine receptor (AChR)
      antibody and improved with oral intake of prednisolone. In contrast, the second
      case showed no elevation of ganglionic AChR antibody titer and had poor response
      to immunomodulatory therapy. These two cases indicate that chronic AAG may be
      treatable by immunomodulatory therapy, and have relevance to SS.

PMID- 19097827
TI  - A novel chromogenic medium for isolation of Pseudomonas aeruginosa from the sputa
      of cystic fibrosis patients.
AB  - BACKGROUND: A novel chromogenic medium for isolation and identification of
      Pseudomonas aeruginosa from sputa of cystic fibrosis (CF) patients was evaluated
      and compared with standard laboratory methods. METHODS: One hundred sputum
      samples from distinct CF patients were cultured onto blood agar (BA), Pseudomonas
      CN selective agar (CN) and a Pseudomonas chromogenic medium (PS-ID). All Gram
      negative morphological variants from each medium were subjected to antimicrobial
      susceptibility testing, and identification using a combination of biochemical and
      molecular methods. RESULTS: P. aeruginosa was isolated from 62 samples after 72 h
      incubation. Blood agar recovered P. aeruginosa from 56 samples (90.3%) compared
      with 59 samples (95.2%) using either CN or PS-ID. The positive predictive value
      of PS-ID (98.3%) was significantly higher than growth on CN (88.5%) for
      identification of P. aeruginosa (P<0.05). CONCLUSIONS: PS-ID is a promising
      medium allowing for the isolation and simultaneous identification of P.
      aeruginosa from sputa of CF patients.

PMID- 19097828
TI  - Comment on: severe hemolytic anemia and fatal hepatic failure associated with
      nimesulide.

PMID- 19097829
TI  - Chronic pancreatitis: report from a multicenter Italian survey (PanCroInfAISP) on
      893 patients.
AB  - BACKGROUND: No data on chronic pancreatitis in Italy are available yet. AIM: To
      evaluate demographic, clinical, diagnostic and therapeutic aspects in patients
      suffering from chronic pancreatitis. PATIENTS AND METHODS: Eligible patients were
      prospectively enrolled from 2000 to 2005. Information concerning demographic
      data, lifestyle risk factors, family and clinical history, associated factors
      (alcohol, autoimmunity, cystic dystrophy of the duodenal wall, obstruction,
      genetic mutations) concomitant diseases, diagnostic findings, and
      pharmacological, endoscopic and surgical therapy were gathered. RESULTS: 893
      patients (74% males, mean age 53.7+/-15.2 years) were evaluated. 519/859 patients
      (60%) were drinkers and 555/840 (66%) were smokers. A strong positive correlation
      between drinking and cigarette consumption (R=0.53; p<0.0001) was found. Heavy
      alcohol consumption (>80g of alcohol/day for more than 5 years) was considered
      the most important risk factor in 300 patients (34%), obstruction in 238 (27%),
      alcohol and obstruction in 82 (9%), autoimmunity in 34 (4%), cystic dystrophy of
      the duodenal wall/groove pancreatitis in 55 (6%), gene mutations in 36 (4%), and
      none (idiopathic) in 148 (17%). Bile stones were diagnosed in 287 patients (33%)
      and cholecystectomy was performed in 329 patients (38%). Pancreatic
      calcifications were diagnosed in 547/879 patients (62%). Pancreatic surgery was
      performed in 273 patients (31%). Endoscopic sphincterotomy was performed in 371
      patients (42%). Exocrine and endocrine insufficiency were found, respectively, in
      373/834 (45%) and 275/885 patients (31%). CONCLUSIONS: An unexpected low
      frequency of alcohol abuse and new emerging associated risk factors for chronic
      pancreatitis were observed in Italy.

PMID- 19097830
TI  - Ascending hypopigmentation of the forearm following injection of triamcinolone.

PMID- 19097831
TI  - Visual development in infants: visual complications of periocular haemangiomas.
AB  - Periocular haemangioma of childhood can severely impact visual development.
      OBJECTIVE(S): To review our experience with 20 periocular haemangioma patients;
      to review infant ocular development in the context of periocular capillary
      haemangioma; to identify early clinical warning signs that may precede
      devastating visual outcomes in the absence of timely management and to review our
      experience with surgical debulking for the treatment of selected periocular
      haemangioma. DESIGN: Retrospective case series. INTERVENTIONS: Twenty children
      with congenital periocular haemangiomas received care by a multidisciplinary team
      consisting of doctors from the specialties ophthalmology, plastic surgery,
      paediatrics and dermatology. The patients were separated by age at presentation
      to our centre (<or=1 year and >1 year). Based on consensus amongst the team,
      certain patients were considered to be at high risk for development of amblyopia,
      permanent cortical visual change or blindness. These patients were scheduled for
      urgent surgical excision or debulking. The effect of treatment on visual
      development over time was evaluated. RESULTS: Patients presenting to our centre
      after 1 year of age were more likely to have amblyopia (75% vs. 0% if presenting
      at <or=1 year of age) and were more likely to have had a series of failed
      interventions. Lesions ranged in size from 5 to 105 mm, with four patients having
      lesions that were described as 'massive'. Surgical debulking was performed in 12
      patients. Mean time to surgery from the decision to operate was 7.8 days (in the
      'high risk' <or=1-yr group), and mean patient age at surgery was 2.5 months. No
      complications were incurred during surgical debulking. CONCLUSION: Early
      identification and multidisciplinary treatment of 'high risk' periocular
      haemangiomas, at imminent risk of causing amblyopia, is essential. Some 'high
      risk' lesions are clinically deceiving and display an apparent open visual axis.
      Early surgical debulking of these lesions can provide immediate decompression of
      the globe and allow for preservation of normal vision. Conversely, a 1-2-week
      period of visual deprivation, in children under 2 years of age, can result in
      permanent cortical visual deficits.

PMID- 19097832
TI  - If the scan fits--evacuate!

PMID- 19097833
TI  - The efficacy and safety of concurrent chemoradiotherapy for maxillary sinus
      squamous cell carcinoma patients.
AB  - OBJECTIVE: Combined treatment modality, e.g., definitive surgery followed by
      radiotherapy (RT) and definitive RT with concurrent chemotherapy, has been
      applied for advanced maxillary sinus squamous cell carcinoma (MSSCC) patients to
      obtain a better survival with organ preservation in Japan. METHODS: The outcome
      of 40 patients with MSSCC between 1991 and 2007 in our institute was analyzed
      retrospectively. There were 36 males and 4 females, the average age being 59.5
      years (ranging from 34 to 81 years). The median follow-up time was 66.1 months.
      All the patients had received a combined treatment consisting of definitive
      surgery, RT, and intra-arterial or systemic chemotherapy. The chemotherapeutic
      regimen was different depending on the performance status and/or complications of
      the patients. Since 1998, concurrent chemoradiotherapy with cisplatin, 5
      fluorouracil, methotrexate and leucovorin regimen (CCRT-PFML) instead of neo
      adjuvant chemotherapy has been applied. RESULTS: The overall 5-year survival rate
      was 59.2%, the 5-year disease-specific survival rate was 71.7%, and the 5-year
      organ preservation survival rate was 42.4%. In the group receiving CCRT-PFML, the
      overall 5-year survival rate was 60.0%, the 5-year disease-specific survival rate
      was 76.0%, and the 5-year organ preservation survival rate was 60.3%. CONCLUSION:
      CCRT-PFML for advanced MSSCC patients is feasible to preserve the organs without
      reducing the survival rate.

PMID- 19097834
TI  - Reversible uncal herniation in a neonate with a large MCA infarct.
AB  - Uncal herniation due to a large cerebral infarct is well-described in adults,
      with high rates of morbidity and mortality. This phenomenon, however, has not
      been previously reported in neonates. We present a newborn male delivered via
      cesarean section with difficult extraction who presented with frequent seizures.
      He was found to have an acute left MCA territory infarct secondary to an M1
      occlusion detected on MRI/MRA. He became lethargic and developed a left uncal
      herniation on CT at 72h of life. He was treated medically with osmolar agents and
      hemodynamic support, and had resolution of the herniation on CT at 120h of life.
      At 19 months he had residual moderate right hemiparesis with only mild gait
      disturbance and mild speech delay. As seen in this case, uncal herniation, though
      rare, may occur in neonates. Also, the outcome for this neonate was much better
      than for typical adults with a similar disease course.

PMID- 19097835
TI  - [Infective endocarditis due to Bartonella henselae following a rupture of a
      cerebral aneurysm].
AB  - We report a case of severe aortic bicuspid valve endocarditis, revealed by global
      cardiac failure without fever, in a 38-year-old man who had developed cerebral
      mycotic aneurysms nine months earlier. PCR analysis of the excised aortic valve
      and serological tests (even 9 months earlier) were positive for Bartonella
      henselae. A combination of intravenous then oral doxycyclin at 200mg/day and
      intravenous gentamycin at 90mg/day was given for 6 and 2 weeks respectively. The
      evolution was favorable on follow-up, 12 months after completion of the therapy.
      Only 49 cases of B. henselae endocarditis have been reported to date, none with
      associated mycotic aneurysm but most often located on the bicuspid aortic valve,
      and usually with severe valvular damage due to late diagnosis.

PMID- 19097836
TI  - Dual-source computed tomography: estimation of radiation exposure of ECG-gated
      and ECG-triggered coronary angiography.
AB  - PURPOSE: The aim of the study was to estimate radiation exposure of coronary
      calcium scoring and angiography using ECG-gated and ECG-triggered dual-source
      computed tomography. MATERIALS AND METHODS: An Alderson Rando phantom equipped
      with thermoluminescent dosimeters was used for all dose measurements. Effective
      dose was calculated according to ICRP 103. Radiation exposure was performed on a
      dual-source computed tomography (DSCT) scanner with standard protocols for
      calcium scoring (DSCT-Ca) and coronary angiography (DSCTA) at different heart
      rates (40-100 beats/min). Furthermore, a scanning protocol with ECG-triggering as
      well as a standard chest CT scan were evaluated. RESULTS: Depending on gender,
      heart rate and ECG-pulsing, the effective dose of a complete cardiac DSCT (DSCT
      Ca and DSCTA) scan varies from 10.2 to 32.6mSv. The effective radiation dose
      increased significantly with lower heart rates (p<0.035). ECG-pulsing reduced the
      radiation exposure significantly in DSCTA (p<0.001). Due to breast tissue in the
      primary scan range, females' doses showed an increase up to 69.9% compared to
      males in scan protocols without ECG-pulsing. Prospective ECG-triggered DSCTA
      resulted in estimated effective doses from 2.8mSv (males) to 4.1mSv (females).
      CONCLUSION: The ECG-pulsing technique has proven its effectiveness to reduce
      effective dose in coronary CT angiography and is recommended for all patients
      with regular heart rates. The patient's heart rate influences the radiation
      exposure with a significant decrease at higher heart rates. Due to its lower
      dose, ECG-triggered DSCTA should be implemented for special indications, i.e. for
      diagnosis of pathologies of the aortic root and the ascending aorta.

PMID- 19097837
TI  - Oculomotor paralysis: 3D-CISS MR imaging with MPR in the evaluation of neuralgic
      manifestation and the adjacent structures.
AB  - PURPOSE: To evaluate the value of three-dimensional (3D) constructive
      interference in steady-state (CISS) magnetic resonance (MR) imaging with multi
      planar reconstruction (MPR) in displaying the relationship between the oculomotor
      nerve and its adjacent structures for patients with oculomotor paralysis.
      MATERIALS AND METHODS: 17 consecutive patients with oculomotor paralysis were
      examined with 3D-CISS and conventional spin-echo (SE) sequences on a 1.5-Tesla MR
      system. Original transverse and MPR images were used for image interpretation.
      The features of the oculomotor nerve and its adjacent structures were identified.
      The diagnosis was surgically confirmed in all patients. RESULTS: Through 3D-CISS
      with MPR images, obvious relationship of the oculomotor nerve and its adjacent
      structures was demonstrated on 17 patients. Of those oculomotor nerves, 15 were
      compressed by the arteries (n=15), one by the craniopharyngioma (n=1), and
      another one by the neurofibroma (n=1). CONCLUSION: 3D-CISS MR imaging with MPR
      provides an excellent way to characterize the relationship between the nerve and
      its adjacent structures in the cisternal segment of the oculomotor nerve in the
      patients with oculomotor paralysis. Moreover, this method shows anatomical
      details for imaging diagnosis and surgical procedure.

PMID- 19097838
TI  - A case of osteitis due to Staphylococcus aureus and Arcanobacterium bernardiae
      coinfection.
AB  - Arcanobacterium bernardiae human infections remain rare. Only 2 reports are
      described in the literature. We report on an immunocompetent patient with a long
      history of chronic osteitis who developed a polymicrobial infection of the knee.
      The initial isolation of Staphylococcus aureus confounded the diagnosis of A.
      bernardiae infection, which underlines the need for extended period of incubation
      and subcultures of enriched liquid culture media. A. bernardiae is a new
      bacterium implicated in osteoarticular infections.

PMID- 19097839
TI  - A simple and rapid nested polymerase chain reaction-restriction fragment length
      polymorphism technique for differentiation of pathogenic and nonpathogenic
      Leptospira spp.
AB  - A rapid and specific nested polymerase chain reaction-restriction fragment length
      polymorphism (PCR-RFLP) has been developed to detect and differentiate pathogenic
      and nonpathogenic Leptospira spp. Leptospiral genomic DNA was extracted from
      suspected human sera using an improved method of standard phenol-chloroform, and
      specific primers have been used to amplify 16S ribosomal RNA from all pathogenic
      and nonpathogenic Leptospira spp. The PCR products of all nonpathogenic species
      were digested with ApoI enzyme, but not pathogenic. To evaluate this assay, we
      analyzed 283 serum samples collected from suspected patients with leptospirosis.
      Nested PCR assay confirmed that 42 (14.8%) of 283 samples harbored Leptospira
      infection, and RFLP assay confirmed 38 (90.5%) of 42 and 4 (9.5%) of 42 positive
      cases had pathogenic and nonpathogenic Leptospira spp., respectively. Based on
      sequencing results, Leptospira interrogans, Leptospira kirschneri, and Leptospira
      wolffii and nonpathogenic Leptospira biflexa and Leptospira genomospecies 3 have
      been detected among analyzed samples. The nested PCR-RFLP assay developed in this
      study fulfills this requirement in the early stage of infection.

PMID- 19097840
TI  - Distribution of capsular serotypes and macrolide resistance mechanisms among
      macrolide-resistant Streptococcus pneumoniae isolates in Korea.
AB  - The mechanism of macrolide resistance was investigated in 251 Streptococcus
      pneumoniae isolates with reduced susceptibility to erythromycin (erythromycin
      resistant S. pneumoniae [ERSP]) collected during the period from 2000 to 2004 in
      Korea. Among these strains, erm(B) was the most prevalent pneumococcal macrolide
      resistance genotype. In particular, dual mechanisms of both the erm(B) and mef(A)
      genes were detected in 77 (30.7%) of 251 ERSP isolates. All of the 77 ERSP
      isolates, with dual erm(B) and mef(A), showed resistance to 2 or more
      antimicrobial agents, including penicillin, cefotaxime, clindamycin,
      tetracycline, and levofloxacin. Serotypes 19F, 23F, 19A, 14, 11A, 6B, 6A, and 9V
      accounted for 73.3% of ERSP isolates. Most of the strains with serotypes 19F
      (77.2%) or 19A (87.5%) had the dual erm(B) and mef(A) genes. The prevalence and
      spread of serotype 19F or 19A isolates may have contributed to the high rate of
      macrolide-resistant pneumococci in Korea. In addition, we identified the
      emergence of a macrolide-nonsusceptible nonvaccine serotype 35B, which carries
      mef(A)-mediated resistance to macrolides. These findings emphasize the need for a
      continuous monitoring of macrolide-resistant S. pneumoniae in Korea.

PMID- 19097841
TI  - Identification of Old World Leishmania spp. by specific polymerase chain reaction
      amplification of cysteine proteinase B genes and rapid dipstick detection.
AB  - We used the cysteine proteinase B (cpb) gene family of the trypanosomatid genus
      Leishmania as a target to develop rapid, specific, and easy-to-use polymerase
      chain reaction (PCR) tests to discriminate Leishmania infantum, Leishmania
      donovani, Leishmania tropica, Leishmania aethiopica, and Leishmania major.
      Identification of all 5 Old World species and validation of intraspecies
      variability are features lacking in other species-specific PCRs. Amplicon
      analysis was done on agarose gels and was further simplified by using an
      oligochromatography dipstick to detect L. infantum and L. donovani products.
      Because the analytical sensitivity is lower than that of certain other species-
      and genus-specific PCRs, our assays are especially valuable for use on cultured
      isolates or directly on cryostabilates. As such, they can be implemented by
      research and health centers having access to culturing, DNA isolation, and PCR.

PMID- 19097842
TI  - The analysis of verbal interaction sequences in dyadic clinical communication: a
      review of methods.
AB  - OBJECTIVE: To identify methods available for sequential analysis of dyadic verbal
      clinical communication and to review their methodological and conceptual
      differences. METHODS: Critical review, based on literature describing sequential
      analyses of clinical and other relevant social interaction. RESULTS: Dominant
      approaches are based on analysis of communication according to its precise
      position in the series of utterances that constitute event-coded dialogue. For
      practical reasons, methods focus on very short-term processes, typically the
      influence of one party's speech on what the other says next. Studies of longer
      term influences are rare. Some analyses have statistical limitations,
      particularly in disregarding heterogeneity between consultations, patients or
      practitioners. Additional techniques, including ones that can use information
      about timing and duration of speech from interval-coding are becoming available.
      CONCLUSION: There is a danger that constraints of commonly used methods shape
      research questions and divert researchers from potentially important
      communication processes including ones that operate over a longer-term than one
      or two speech turns. Given that no one method can model the complexity of
      clinical communication, multiple methods, both quantitative and qualitative, are
      necessary. PRACTICE IMPLICATIONS: Broadening the range of methods will allow the
      current emphasis on exploratory studies to be balanced by tests of hypotheses
      about clinically important communication processes.

PMID- 19097843
TI  - Walking on prescription: the utility of a pedometer pack for increasing physical
      activity in primary care.
AB  - OBJECTIVE: This study used a multi-method approach to examine the effectiveness
      of a pedometer-based intervention delivered by health professionals for
      increasing walking. METHODS: Pedometer packs were distributed to 374 patients who
      undertook a 12-week walking programme. Changes in walking were assessed at three
      months (using self-reported step-counts [n=139] and questionnaire data [n=104])
      and at six months (using patient questionnaire data [n=112]). Qualitative data
      were collected at both time points to identify underlying mechanisms. RESULTS:
      After 12 weeks patients had increased their step-counts by 4532 steps/day
      (p<.001) and at six months were achieving 2977 more steps/day (equivalent to
      around 30 min/day) than at baseline. Over half the patients reported achieving
      this target on at least 5 days/week. Qualitative data indicated that the
      pedometer pack was perceived to be most effective when patients were ready to
      change and when ongoing support was made available. CONCLUSION: These findings
      support the use of pedometer-based interventions in primary care and suggest that
      the pedometer pack could lead to sustainable changes in walking. Further
      investigation, using a randomised controlled trial design, is warranted. PRACTICE
      IMPLICATIONS: Provision of social support and accurate identification of patient
      readiness to change are important considerations in future implementation of the
      intervention.

PMID- 19097844
TI  - The development of a treatment guideline for childhood malaria in rural Southwest
      Nigeria using participatory approach.
AB  - OBJECTIVE: To describe the development of a treatment guideline for the effective
      case management of malaria in children at the home level. METHODS: Thirty-three
      mothers selected from 11 communities in a rural health district, community
      members and the research team developed a guideline for treatment of malaria at
      home by caregivers using a participatory approach. This was done in phases using
      modified focus group discussion sessions. Suggested ideas were depicted in
      illustrations by a graphic artist. RESULTS: A guideline which illustrated the
      presentation of clinical types of malaria, the appropriate steps to take for each
      type and the correct dosage schedule of chloroquine (based on the age of the
      child) for treatment of uncomplicated malaria was developed. The guideline was in
      cartoon format and the script in the local language. CONCLUSION: Use of a
      participatory approach was found acceptable and effective in the development of
      the guideline. This approach is therefore recommended irrespective of the target
      population or the intervention to be developed. Practice implications Preparation
      of educational materials with contributions from end users does not only build
      capacity at the local level but also increases the acceptability and ownership of
      such materials.

PMID- 19097845
TI  - [Penile block with ropivacaine].

PMID- 19097846
TI  - [Assessment of hygiene practices in anaesthesia between 1998 and 2007 in
      Lorraine].
AB  - OBJECTIVES: To study the assessment of hygiene practices in anaesthesia in
      Lorraine between 1998 and 2007, after recommendations from the French Society of
      Anaesthesia and Reanimation (SFAR) in December 1997, and different local actions.
      STUDY DESIGN: Two surveys performed at a nine-year interval in Lorraine
      hospitals. POPULATION AND METHOD: Questionnaires about risk infection management
      and hygiene practices were sent by post to all anaesthetists, nurse anaesthetists
      and recovery room nurses in 1998 (n=279) and in 2007 (n=259). RESULTS: Between
      the two surveys multidrug-resistant bacteria signalling, movements of the staff
      in operating rooms, septic isolation protocol and management of single-use
      disposable anaesthesia material have been improved (p<0.05). Central venous
      catheters are less performed in recovery rooms and rings wearing decreased by 16%
      (p<0.05). Wearing of nonsterile gloves for peripheral venous catheter and
      intubation is not generalized (p<0.05). About half of the hospitals have cleanup
      procedures of anaesthesia furniture. Washing of hands by anaesthesia staff is not
      sometimes respected but it's more frequent for medicine preparation and between
      two operations. A good skin disinfection (cleaning - rinsing - drying -
      antiseptic) is more recurrent in 2007 (61.4%) than in 1998 (41.9%) for arterial
      catheter. Wearing of glasses for intubation is each times rare, about 15%.
      CONCLUSION: Hygiene practices in anaesthesia in Lorraine have been improved
      between the two surveys by recommendations from the Sfar and the work of the
      Antenne Regional de Lorraine (audits, manuals, formations). Promising progress
      has been made but some points must still be worked on.

PMID- 19097847
TI  - [Severe hyponatraemia and central pontine myelinolysis: be careful with other
      factors!].
AB  - Central pontine myelinolysis covers very different clinical aspects, ranging from
      discrete tremor to quadriplegia. Rapid correction of hyponatraemia is a well
      known risk factor, particularly in chronic alcohol abusers. We describe the case
      of a 46-year-old chronic alcoholic, suffering from denutrition. He developed a
      quadriplegia and a facial diplegia two weeks after a slow correction of a chronic
      hyponatraemia associated with hypokalaemia. Central pontine myelinolysis was
      formally diagnosed by MRI findings. In our case, the correction of hyponatraemia
      is not the only causal agent of this syndrome; hypokalaemia and denutrition seem
      to be predisposing factors too. For these reasons, glial cells are more
      vulnerable to osmotic variations. Despite of severe initial symptoms, the
      evolution was favourable with a quasi complete recovery.

PMID- 19097848
TI  - [Duration of antibiotic therapy for ventilator-associated pneumonia: comparison
      of 7 and 10 days. A pilot study].
AB  - OBJECTIVE: To compare the efficiency of a 7-day antibiotics regimen with a 10-day
      regimen for ventilator-associated pneumonia (VAP). STUDY DESIGN: Prospective
      randomized study. PATIENTS AND METHODS: Adults patients ventilated for more than
      48 hours in the intensive care unit (ICU) with a clinical diagnosis of VAP
      documented by positive quantitative cultures of tracheal aspiration were included
      in this study. All included patients were randomized in two groups. Ten-day
      group: 10 days antibiotic therapy, and 7-day group: 7 days antibiotic therapy.
      Primary judgment criteria were 14- and 28-day mortality, the number of days
      without antibiotics. Secondary judgments criteria were rate of recurrent
      pulmonary infection, the evolution of the clinical pulmonary infection scores
      (CPIS), the length of ICU stay and the length of mechanical ventilation. RESULTS:
      Thirty patients were included in this study (16 in the 10-day group and 14 in the
      7-day group). The demographic and clinical characteristics of the groups assigned
      to receive antibiotic therapy for 7 or 10 days were generally similar. The 14-day
      and 28-day mortality rate following VAP onset were 31.2 and 37.5% in the 10-day
      group and 7.1 and 35.7% in the 7-day group. The difference was not significant.
      The number of day without antibiotics and without mechanical ventilation turned
      out: 1.75 and 2.06 days versus 4.14 and 3.43 days in the 10-day group and 7-day
      group respectively, the recurrent rate of pulmonary infection (12.5% versus
      14.3%, p=0.6), the length of stay in the ICU (27.7 days versus 26.0 days, p=0.8)
      and the evolution of the CPIS were no different in the two groups. CONCLUSION: In
      patients with microbiologically confirmed VAP who received appropriate empirical
      antibiotic therapy, a 7-day antibiotic regimen was as efficient clinically and
      microbiologically as a 10-day antibiotic regimen with a reduction of antibiotic
      use.

PMID- 19097849
TI  - [Mastocytosis and anaesthesia].
AB  - Mastocytosis are characterized by an accumulation of abnormal mast cells in
      various tissues. Their incidence is estimated at 1/150,000 patients. Pure
      cutaneous mastocytosis which are mainly observed during childhood may resolve
      spontaneously during adolescence, whereas systemic mastocytosis involving one or
      more organs or tissues are more observed in adults. The initial event leading to
      mastocytosis is believed to be related to activating mutations in c-kit receptor,
      thus resulting in increased proliferation of mast cells precursors, migration in
      various tissues and degranulation leading to clinical signs. This nosologic
      entity does not belong to allergic diseases. Their perioperative management
      involves a multidisciplinary approach. The degranulation of mast cells with
      subsequent clinical symptoms can be triggered by psychological, chemical,
      traumatic, physical (rubbing, extreme temperatures...) agents. Avoiding these
      triggers should be realized whenever possible according to each patient. The
      premedication has not proven its efficiency. Tryptase measurement is part of the
      preoperative biological assessment. The clinical signs severity is related to the
      cardiovascular homeostasis disturbances (arterial hypotension, cardiovascular
      collapse, cardiac arrest). The cardiovascular symptoms do not correlate to the
      cutaneous versus systemic description of the disease. The drug of choice for the
      treatment of the severe cardiovascular signs is epinephrine associated to
      vascular loading. The aim of this literature review is to suggest the different
      modalities of perioperative care of patients with mastocytosis.

PMID- 19097851
TI  - Effects of femoral component size on proximal tibial strain with anatomic
      graduated components total knee arthroplasty.
AB  - Survivorship in total knee arthroplasty (TKA) is multifactorial and dependent
      upon alignment, ligament balance, patient characteristics, and implant factors.
      The contribution of each factor leading to implant loosening is not well known.
      This study defined the effect of femoral component sizing relative to tibial size
      on loading patterns in the proximal tibia. Changes in strain were measured in
      tibiae implanted with appropriately sized metal-backed tibial components loaded
      with 2 sizes of femoral components. Significant increases of shear strain up to
      126% were measured in peripheral regions of the tibia when loaded with a larger
      vs a smaller femoral component. Increased peripheral loading in the proximal
      tibia could predispose to a higher risk of cancellous overload and failure.
      Limiting stress concentrations in the periphery of the proximal tibia by
      considering sizing relationships between femoral and tibial components may
      decrease osseous strains and the likelihood of bony overload in TKA.

PMID- 19097850
TI  - [Lower respiratory tract infections with influenza and respiratory syncytial
      viruses in hospitalized elderly patients during the 2005-2006 winter season].
AB  - OBJECTIVES: To assess the proportion of lower respiratory tract infections (LRTI)
      attributable to influenza virus and respiratory syncytial virus (RSV) during the
      2005-2006 winter period, among hospitalized elderly in a geriatric unit of a
      French hospital near Paris and and describe the characteristics of these
      infections. METHODS: In a geriatric unit with 115 beds, distributed as 14 in
      acute care (ACF), 21 in rehabilitation and intermediate-care (RICF) and 80 in
      long-term-care-facilities (LTCF), all patients over age 65 with LRTI were
      enrolled during a winter. Clinical and biological parameters were recorded
      including paired serology for influenza virus and RSV. RESULTS: 54 LRTI concerned
      47 patients were recorded. 50 paired serums were analysed. Influenza virus or RSV
      were found in 17 cases (34%). The distribution of the cases was as follows:
      Influenza A in 5 cases, Influenza B in 3 cases, a co-infection with influenza A
      and B in 4 cases, RSV in 3 cases and co-infections with influenza and RSV in 2
      cases (influenza A and RSV in one case and influenza A and B and RSV in the other
      case). 7 cases concerned patients in ACF, in 3 cases patients were in RICF and in
      7 cases patients were in LTCF. 15 cases were nosocomial infections. 11 patients
      infected by influenza virus were vaccined. It was concluded as bronchitis in 8
      cases, interstitial pneumonia in 6 cases and alveolar pneumonia in 3 cases.
      Antibiotics were prescribed in 11 cases. In one case the evolution was
      unfavourable with death. Patients with influenza or RSV infections had
      significantly more rales and rhonchi compared with patients non infected by these
      virus (p<0.05). CONCLUSION: Influenza and RSV are an important cause of LRTI in
      elderly during the winter months, influenza infections can occurring among
      vaccinated elderly. It seems necessary to achieve further clinical studies about
      LRTI in elderly and to study the impact of rapid diagnostic tests to improve the
      management of these infections.

PMID- 19097852
TI  - Attentional bias to moving spiders in spider fearful individuals.
AB  - We investigated if an attentional bias for spiders in spider fearful individuals
      (SFs) can also be found for moving spiders, rather than static images. In Study
      1, 28 SFs and 33 non-anxious controls (NACs) participated in a modified version
      of the dot probe paradigm: they had to react to a probe that appeared either in
      the next, previous, or side position of a spider's or a wheel's path. 24 SFs and
      29 NACs participated in Study 2, in which a fourth, highly predictable, probe
      position was added. We expected that moving spiders would capture the attention
      of SFs. In addition, we tested whether SFs try to predict the movement of the
      spider to make it less threatening. As expected, SFs showed an attentional bias
      towards moving spiders. However, both groups reacted fastest to unpredictable
      movements, indicating that SFs and NACs alike anticipate unpredictable spider
      movements.

PMID- 19097853
TI  - Improvement of cardiac CT reconstruction using local motion vector fields.
AB  - The motion of the heart is a major challenge for cardiac imaging using CT. A
      novel approach to decrease motion blur and to improve the signal to noise ratio
      is motion compensated reconstruction which takes motion vector fields into
      account in order to correct motion. The presented work deals with the
      determination of local motion vector fields from high contrast objects and their
      utilization within motion compensated filtered back projection reconstruction.
      Image registration is applied during the quiescent cardiac phases. Temporal
      interpolation in parameter space is used in order to estimate motion during
      strong motion phases. The resulting motion vector fields are during image
      reconstruction. The method is assessed using a software phantom and several
      clinical cases for calcium scoring. As a criterion for reconstruction quality,
      calcium volume scores were derived from both, gated cardiac reconstruction and
      motion compensated reconstruction throughout the cardiac phases using low pitch
      helical cone beam CT acquisitions. The presented technique is a robust method to
      determine and utilize local motion vector fields. Motion compensated
      reconstruction using the derived motion vector fields leads to superior image
      quality compared to gated reconstruction. As a result, the gating window can be
      enlarged significantly, resulting in increased SNR, while reliable Hounsfield
      units are achieved due to the reduced level of motion artefacts. The enlargement
      of the gating window can be translated into reduced dose requirements.

PMID- 19097854
TI  - Automatic segmentation of magnetic resonance images using a decision tree with
      spatial information.
AB  - Here we proposed an automatic segmentation method based on a decision tree to
      classify the brain tissues in magnetic resonance (MR) images. Two types of data -
      phantom MR images obtained from IBSR (http://www.cma.mgh.harvard.edu/ibsr) and
      simulated brain MR images obtained from BrainWeb
      (http://www.bic.mni.mcgill.ca/brainweb) - were segmented using an automatic
      decision tree algorithm to obtain images with improved visual rendition. Spatial
      information on the general gray level (G), spatial gray level (S), and two
      dimensional wavelet transform (W) was combined in-plane in two coordinate systems
      (Euclidean coordinates (x, y) or polar coordinates (r, theta)). The decision tree
      was constructed based on a binary tree with nodes created by splitting the
      distribution of input features of the tree. The spatial information obtained from
      MR images with different noise levels and inhomogeneities were segmented to
      compare whether the use of a decision tree improved the identification of human
      anatomical structures in a neuroimage. The average accuracy rates of segmentation
      for phantom images with a noise variation of 15 gray levels were 0.9999 and
      0.9973 with spatial information (G, x, y, r, theta) and (S, x, y, r, theta),
      respectively, and 0.9999 and 0.9819 with spatial information (G, x, y, S, r,
      theta) and (W, x, y, G, r, theta). The average accuracy rates of segmentation for
      simulated MR images with a noise level of 5% were 0.9532 and 0.9439 with spatial
      information (G, x, y, r, theta) and (S, x, y, r, theta), respectively, and 0.9446
      and 0.9287 with spatial information (G, x, y, S, r, theta) and (W, x, y, G, r,
      theta). The accuracy rates of segmentation were highest for both simulated
      phantom and brain MR images, having the lowest noise levels, from a reduction of
      overlapping gray levels in the images. The accuracies of segmentation were higher
      when the spatial information included the general gray level than when it
      included the spatial gray level, which in turn were higher than when it included
      the wavelet transform. Furthermore, the performance of segmentation was also
      evaluated with a boundary detection methodology that is based on the Hausdorff
      distance to compare with the mean computer to observer difference (COD) and mean
      interobserver difference (IOD) for gray matter (GM), white matter (WM), and all
      areas (ALL) from images segmented using the decision tree. The values of mean COD
      are similar and around 12mm for GM segmented using the decision tree. Our
      segmentation method based on a decision tree algorithm presented an easy way to
      perform automatic segmentation for both phantom and tissue regions in brain MR
      images.

PMID- 19097855
TI  - Delayed vascular injury and severe respiratory distress as a rare complication of
      a central venous catheter and total parenteral nutrition.
AB  - Complications related to central venous catheters (CVCs) in the postoperative
      period can be fatal. We recently had a case of bilateral pleural effusion and
      respiratory distress caused by delayed vascular injury. A 79-y-old Japanese woman
      was admitted to our hospital because of advanced gastric carcinoma. A multiple
      lumen CVC was placed through the left subclavian vein 1 d before surgery for
      postoperative nutritional management. The patient suddenly complained of dyspnea,
      and the chest X-ray film revealed right massive pleural effusion. Although the
      patient's symptoms soon disappeared after the thoracentesis, she again developed
      severe respiratory distress, and an endotracheal intubation was performed and her
      respiration was managed by mechanical ventilation. Computed tomographic scan of
      the chest revealed a displacement of the tip of the CVC out of the wall of the
      superior vena cava, mediastinitis, and leakage of intravenous fluid, which may
      have been caused by delayed vascular injury due to the CVC. The CVC was removed
      immediately after the diagnosis of delayed vascular injury at 10 d after surgery.
      The patient soon recovered with conservative treatment and was discharged from
      the hospital 43 d after surgery. This case highlights an extremely rare
      presenting complication of CVC placement and total parenteral nutrition.

PMID- 19097856
TI  - Plum juice, but not dried plum powder, is effective in mitigating cognitive
      deficits in aged rats.
AB  - OBJECTIVE: Normal aging in animals and humans is accompanied by a decline in
      cognitive performance that is thought to be due to the long-term effects of
      oxidative stress and inflammation on neurologic processes. Previous findings have
      suggested that protection against age-related cognitive declines may be achieved
      by increasing the dietary intake of fruits and vegetables, especially those that
      are high in antioxidant activity, such as blueberries and strawberries. The
      objective of this study was to investigate supplementation with Prunus domestica
      L. in mitigating age-related deficits in cognitive function. METHODS: We
      investigated the effects of supplementation with P. domestica L., consumed as a
      2% dried plum (i.e., prune) powder or 100% plum juice for 8 wk, in mitigating age
      related deficits in cognitive function in aged Fischer 344 rats. RESULTS: Rats
      that drank plum juice from 19 to 21 mo of age had improved working memory in the
      Morris water maze, whereas rats fed dried plum powder were not different from the
      control group, possibly due to the smaller quantity of phenolics consumed in the
      powder group compared with the juice group. CONCLUSION: These results are
      discussed in relation to the amount and type of phenolics present in the plum
      products and in relation to other dietary intervention studies in which cognitive
      benefits have been reported.

PMID- 19097858
TI  - Nutritional therapy for burns in children and adults.
AB  - Burns are a serious injury that requires optimal nutritional support. This review
      discusses the nutritional care for adults and children with major burns. A burned
      patient's metabolism is greatly accelerated with increased requirements for
      energy, carbohydrates, proteins, fats, vitamins, minerals, and antioxidants.
      Early nutrition by parenteral and enteral feedings is vital. Careful assessment
      of the nutritional state of the burn patient is also important to reduce
      infection, recovery time, and long-term sequelae.

PMID- 19097859
TI  - Distribution of tenascin-C, fibronectin and collagen types III and IV during
      regeneration of rat submandibular gland.
AB  - The aim of this study was to determine the localization of tenascin-C,
      fibronectin and collagen types III and IV during regeneration of the rat
      submandibular gland. After 7 days' obstruction, the regenerating glands were
      collected at days 0, 1, 3, 5, 7, 11 and 14 after duct release to study
      regeneration. Immunohistochemical staining revealed that tenascin-C was strongly
      expressed in the epithelial cells of duct-acinar structures at days 0-3, and down
      regulated in its expression from day 5 to 11, though weak expression was detected
      in the intercalated duct and acinar cells of the normal gland. Strong labeling of
      fibronectin was detected around duct-acinar structures during days 0-3 of
      regeneration. Type IV collagen was expressed strongly in the thickened basement
      membrane of acinar cells and duct-acinar structures during days 0-3, but weakly
      around large ducts, though type III collagen was expressed at consistent levels.
      These findings suggest that tenascin-C and fibronectin affect only the duct
      acinar structures, and type IV but not type III collagen is involved in the
      regeneration of acinar cells.

PMID- 19097860
TI  - Age-dependent anticonvulsant action of antagonists of group I glutamate
      metabotropic receptors in rats.
AB  - SUMMARY: Metabotropic glutamate receptors (mGluR) may represent a perspective
      target for anticonvulsant therapy but spectrum of their anticonvulsant effects is
      not sufficiently known. Our study was aimed at comparison of anticonvulsant
      actions of antagonists of mGluR1 and mGluR5 subtypes in immature rats. Seven-, 12
      , 18- and 25-day-old animals were pretreated with mGluR1 antagonist AIDA (1
      20mg/kg i.p.) or mGluR5 antagonist MTEP (5-40 mg/kg i.p.) 30 min before
      pentetrazol administration (100mg/kg s.c.). Two types of motor seizures were
      elicited: minimal, clonic seizures (mS) and generalized tonic-clonic seizures
      (GTCS). mS could be induced only in 18- and 25-day-old rats, and their incidence
      was decreased to 0-50% by nearly all doses of either drug in 18- but not in 25
      day-old rats. GTCS were observed in all age groups; higher doses of both
      antagonists specifically suppressed the tonic phase in 7-, 12- and 18-day-old
      rats. The highest efficacy was found in 12-day-old rats; seizure severity was
      significantly decreased even by the 10-mg/kg dose of MTEP and the 2-mg/kg dose of
      AIDA in this age group. In addition, MTEP tended to suppress also the clonic
      phase in 7-day-old rats. Time course of action studied in 12-day-old animals
      demonstrated much longer action of MTEP (more than 4h) than of AIDA (less than
      1h). Administration of AIDA but not MTEP resulted in a paradoxical shortening of
      latencies of seizures even at time intervals when the incidence of the tonic
      phase of GTCS was decreased. Both mGluR antagonists exhibit specific
      anticonvulsant action in rat pups during the first 3 postnatal weeks.

PMID- 19097861
TI  - Reduced fronto-temporal connectivity is associated with frontal gray matter
      density reduction and neuropsychological deficit in schizophrenia.
AB  - OBJECTIVES: A "disconnectivity model" of schizophrenia has been proposed, but it
      is still unclear if white matter abnormalities are associated with gray matter
      changes and if they may be the anatomic substrate of cognitive impairment, which
      is a core symptom of the disorder. The first objective was to detect if white
      matter microstructure alterations in schizophrenia are associated with or
      independent of gray matter change, using an optimized method for white matter
      (Tract-Based Spatial Statistics) and gray matter analyses (whole-brain voxel-wise
      approach). The second objective was to identify the neuropsychological correlates
      of white matter abnormalities in the schizophrenic group, using a comprehensive
      neuropsychological battery. METHODS: In this case-control study 43 schizophrenic
      patients and 43 healthy volunteers were consecutively enrolled and matched for
      age and gender. RESULTS: Fractional anisotropy reduction was found in 6 fronto
      temporal clusters (corrected p-values <0.05) in schizophrenic group in comparison
      with healthy volunteers, and 3 clusters showed fractional anisotropy increase
      (corrected p-values <0.05). Two of the clusters showing reduced fractional
      anisotropy were associated with reduced gray matter density in neuroanatomically
      related regions in schizophrenic subjects (p-values ranging from 0.001 to 0.026).
      Executive, constructional-praxis, and working memory deficits were significant
      predictors of fractional anisotropy reduction in 4 clusters in the schizophrenic
      group (p-values ranging from <0.0001 to 0.0017). CONCLUSIONS: Our data support
      the disconnectivity hypothesis in schizophrenia, enlightening a link between
      reduced fronto-temporal connectivity and "frontal" cognitive deficits. Reduced
      gray matter density may be involved primarily in the pathogenesis of some of
      these disconnected areas.

PMID- 19097862
TI  - Genetic characterisation of the ethambutol resistance-determining region in
      Mycobacterium tuberculosis: prevalence and significance of embB306 mutations.
AB  - Ethambutol (EMB) is a first-line antitubercular drug that inhibits
      arabinogalactan and lipoarabinomannan biosynthesis. Resistance to EMB has
      traditionally been associated with embB mutations, especially in the Met306
      codon. In this study, the region encompassing the embB306 codon in 109
      Mycobacterium tuberculosis clinical isolates (49 EMB-susceptible and 60 EMB
      resistant) was characterised. The occurrence of embB306 mutations was verified
      not only in EMB-resistant isolates (55.0%) but also in EMB-susceptible isolates
      (16.3%), which questions the role of embB306 mutations as determinants of EMB
      resistance. Subsequently, four different embB alleles were created by in vitro
      mutagenesis and were introduced into Mycobacterium smegmatis on a multicopy
      plasmid. To assess the contribution of embB306 mutations to EMB resistance, the
      EMB minimum inhibitory concentration (MIC) of these strains was determined.
      Strains carrying mutant embB306 alleles were able to grow at slightly higher MICs
      compared with the strain carrying the wild-type embB gene. The small MIC increase
      obtained here does not appear to be sufficient to cause high-level EMB
      resistance. The results obtained in the present study suggest that acquisition of
      EMB resistance might be a multistep process in which embB306 mutations may
      represent a first-step in EMB resistance acquisition.

PMID- 19097864
TI  - Treatment of pyogenic (non-tuberculous) spondylodiscitis with tailored high-dose
      levofloxacin plus rifampicin.
AB  - The purpose of this study was to assess the clinical efficacy of high-dose
      levofloxacin plus rifampicin in the empirical treatment of non-tuberculous
      spondylodiscitis in an epidemiological context of low incidence of staphylococcal
      fluoroquinolone resistance. All consecutive adult patients with spondylodiscitis
      (January 2003 to December 2006) were empirically treated with high-dose
      levofloxacin (500 mg every 12 h normalised to renal function and optimised by
      means of therapeutic drug monitoring whenever feasible) plus rifampicin 600 mg
      every 24 h. Trough and peak plasma concentrations were targeted at 1-3 mg/L and 6
      9 mg/L, respectively, to maximise the concentration-dependent activity of
      levofloxacin in bone. Follow-up was performed until 9 months after the end of
      therapy. Forty-eight patients were included. Eleven patients underwent a surgical
      approach for spine stabilisation. Among the 29 bacterial isolates, Staphylococcus
      aureus was the most frequent (65.5%) (all meticillin-susceptible strains).
      Tailored levofloxacin plasma exposure over time was ensured in most cases. Median
      treatment duration was 15.1 weeks. Overall response rates were: 77.1% at the
      intent-to-treat analysis; 84.1% among patients who completed therapy (N=44); and
      96.3% among those receiving targeted therapy against documented levofloxacin
      susceptible isolates (N=27). No patient had evidence of disease relapse at follow
      up. Our findings suggest that high-dose levofloxacin regimens may be highly
      effective in the treatment of non-tuberculous spondylodiscitis and support its
      putative role in combination with rifampicin against S. aureus.

PMID- 19097863
TI  - ksgA mutations confer resistance to kasugamycin in Neisseria gonorrhoeae.
AB  - The aminoglycoside antibiotic kasugamycin (KSG) inhibits translation initiation
      and thus the growth of many bacteria. In this study, we tested the
      susceptibilities to KSG of 22 low-passage clinical isolates and 2 laboratory
      strains of Neisseria gonorrhoeae. Although the range of KSG minimum inhibitory
      concentrations (MICs) was narrow (seven-fold), clinical isolates and laboratory
      strains fell into three distinct classes of KSG sensitivity, susceptible,
      somewhat sensitive and resistant, with MICs of 30, 60-100 and 200 microg/mL,
      respectively. Two genes have previously been shown to be involved in bacterial
      KSG resistance: rpsI, which encodes the 30S ribosomal subunit S9 protein; and
      ksgA, which encodes a predicted dimethyltransferase. Although sequencing of rpsI
      and ksgA from clinical isolates revealed polymorphisms, none correlated with the
      MICs of KSG. Ten spontaneous KSG-resistant (KSG(R)) mutants were isolated from
      laboratory strain FA1090 at a frequency of <4.4x10(-6) resistant colony-forming
      units (CFU)/total CFU. All isolated KSG(R) variants had mutations in ksgA, whilst
      no mutations were observed in rpsI. ksgA mutations conferring KSG resistance
      included four point mutations, two in-frame and one out-of-frame deletions, one
      in-frame duplication and two frame-shift insertions. These data show a narrow
      range of susceptibilities for the clinical isolates and laboratory strains
      examined; moreover, the differences in MICs do not correlate with nucleotide
      polymorphisms in rpsI or ksgA. Additionally, spontaneous KSG(R) mutants arise by
      a variety of ksgA mutations.

PMID- 19097865
TI  - Treatment of experimental osteomyelitis caused by methicillin-resistant
      Staphylococcus aureus with a synthetic carrier of calcium sulphate (Stimulan)
      releasing moxifloxacin.
AB  - The objectives of this study were to assess the efficacy of a synthetic
      semihydrate form of calcium sulphate (Stimulan) in experimental bone infection
      caused by methicillin-resistant Staphylococcus aureus (MRSA). Osteomyelitis was
      induced after inoculation of the test pathogen in the left tibia of 72 New
      Zealand rabbits assigned to the following groups: 18 control rabbits (Group A);
      18 rabbits with Stimulan implanted (Group B); and 36 rabbits with moxifloxacin
      impregnated Stimulan implanted (Group C). Rabbits were sacrificed at weekly
      intervals and cancellous bone was harvested for histopathology and for estimation
      of bacterial growth and concentrations of moxifloxacin. Bacterial growth from
      cancellous bone of Group C was significantly lower than the respective growth of
      Groups A and B on all days of sacrifice. The main histological finding of animals
      in all three groups was a moderate to intense inflammatory reaction accompanied
      by fibrosis. The degree of fibrosis was higher in Group C compared with both
      other groups. Infiltration by giant cells was also observed, which was greater in
      Group C on Day 42. Antibiotic levels in bone were higher for bone samples closer
      to the site of implantation. In conclusion, Stimulan admixed with 10%
      moxifloxacin was very effective in achieving complete eradication of the
      causative pathogen in experimental osteomyelitis caused by MRSA.

PMID- 19097866
TI  - Failure of cefepime therapy in neutropenic patients with extended-spectrum beta
      lactamase-producing Gram-negative bacteraemia.

PMID- 19097867
TI  - Therapeutic options for Burkholderia cepacia infections beyond co-trimoxazole: a
      systematic review of the clinical evidence.
AB  - Burkholderia cepacia complex (BCC) is an important group of pathogens affecting
      patients with cystic fibrosis and chronic granulomatous disease as well as
      immunocompromised and hospitalised patients. Therapeutic options are limited
      owing to high levels of resistance of the organism, either intrinsic or acquired,
      to many antimicrobial agents. Co-trimoxazole (trimethoprim/sulfamethoxazole) has
      been a drug of choice. However, in some cases it cannot be administered because
      of allergic or hypersensitivity reactions, intolerance or resistance. We
      systematically searched for relevant publications including clinical data in
      PubMed and Scopus. The search identified 48 relevant case reports (57 cases) and
      8 cohort studies or trials. Nineteen (33.3%) of 57 patients included in the case
      reports received ceftazidime-based regimens, 14 (73.7%) of whom were cured.
      Meropenem was administered in seven patients (12.3%), one (14.3%) of whom
      improved and five (71.4%) were cured. Seven (12.3%) of 57 cases were treated with
      penicillins, four of which were piperacillin (all had a favourable outcome).
      Based on the data reported in the eight relevant cohort studies or trials
      identified, favourable outcomes were observed in 68.4% (26/38) to 100% (16/16) of
      cases treated with ceftazidime and 66.7% (6/9) of cases treated with meropenem.
      Also, 9/12 (75%) of patients receiving penicillins improved. Thus, Ceftazidime,
      meropenem and penicillins, mainly piperacillin, either alone or in combination
      with other antimicrobial agents, may be considered as alternative options for BCC
      infections, according to the in vitro antimicrobial susceptibility patterns and
      clinical results. However, the available clinical data are not sufficient and
      further clinical experience is required to clarify the appropriateness of these
      antibiotics for BCC infections.

PMID- 19097868
TI  - Pharmacokinetics and tolerance of linezolid for meticillin-resistant
      Staphylococcus aureus mediastinitis in paediatric patients.
AB  - Here we report our experience with four paediatric patients with mediastinitis
      due to meticillin-resistant Staphylococcus aureus (MRSA) following cardiac
      surgery refractory to glycopeptide treatment and treated by linezolid. The
      pharmacokinetics and tolerance of linezolid administered orally or intravenously
      were analysed. Linezolid was administered intravenously at a dosage of 10 mg/kg
      every 8 h and then orally. In oral administration, 10 mg/kg or 15 mg/kg was given
      every 8 h as a powder made by crushing tablets. The linezolid serum trough
      concentration was >or=3.5 mg/L in patients treated by intravenous administration.
      However, with oral administration lower trough levels were detected, including
      patients with an undetectable level (<0.1 mg/L). No significant intolerance or
      drug-related haematological events were reported. We conclude that linezolid,
      with a switch from intravenous to oral administration, could be an effective and
      safe option in paediatric mediastinitis refractory to conventional glycopeptides,
      whilst care must be taken to maintain an adequate dose by monitoring the trough
      concentration.

PMID- 19097869
TI  - Extended-spectrum beta-lactamase-producing Klebsiella pneumoniae in a neonatal
      intensive care unit in Leon, Nicaragua.

PMID- 19097870
TI  - Psychotherapy for personality disorders: short-term day hospital psychotherapy
      versus outpatient individual therapy - a randomized controlled study.
AB  - This article describes the results of an eight-month follow-up investigation from
      a randomized controlled trial of day hospital psychotherapy (DHP) compared with
      outpatient individual psychotherapy (OIP) for patients with personality disorders
      (N=114). The patients were randomly assigned to either 18 weeks of day hospital
      treatment followed by long-term conjoint group and individual therapy (DHP), or
      outpatient individual psychotherapy (OIP). The main outcome measures were
      attrition rate, suicide attempts, suicidal thoughts, self-injury, psychosocial
      functioning, symptom distress, and interpersonal and personality problems. The
      study showed a low dropout rate and a moderate improvement on a broad range of
      clinical measures for both treatments. However, there was no indication of the
      superiority of one treatment over the other. Neither was there any indication
      that day hospital treatment was better for the most poorly functioning patients.
      Further studies will follow this group of patients for the next few years, the
      results of which may have implications for resource allocation and the
      organization of mental health services for patients with personality disorders.

PMID- 19097871
TI  - Prefrontal myo-inositol concentration and visuospatial functioning among diabetic
      depressed patients.
AB  - Patients with diabetes mellitus are reported to be at higher risk for developing
      neuropsychiatric disorders such as dementia and depression. Myo-inositol (mI), a
      neuronal/glial metabolite associated with multiple functions in the brain, has
      been shown to be increased in cognitive disorders, depression and diabetes. This
      study examined whether elevations in dorsolateral (DL) mI of diabetic patients
      with depression were associated with visuospatial deficits. Diabetic and
      depressed patients (n=18) were matched with patients with diabetes but without
      depression (n=20) and control subjects (n=19). Subjects were scored on both the
      recall and recognition tasks of the Rey-Osterreith Complex Figure (ROCF). Proton
      magnetic spectroscopy spectra from bilateral prefrontal white matter voxels were
      used to obtain concentrations of mI. Controls showed negative correlations
      between mI in right DL white matter and recall and recognition subtests. No
      correlation was observed for depressed diabetic patients. Correlations for
      diabetic controls fell midway between the comparison and depressed diabetic
      groups. The expected pattern of association between mI and visuospatial
      impairment in the right DL prefrontal region was seen among healthy controls.
      Progressive weakening of this association across both diabetic groups might be
      related to progressive changes in neural activity that underlies visuospatial
      function.

PMID- 19097872
TI  - [Intestinal obstruction in children due to isolated intestinal malrotation.
      Report of 11 cases].
AB  - The purpose of this study was to determine the clinical significance of children
      presenting with malrotation to develop treatment recommendations. METHODS:
      Records of children undergoing a Ladd procedure were identified in the pediatric
      patient database from 1 June 1996 to 31 March 2007. Patients with intestinal
      obstruction caused by isolated intestinal malrotation were included. The
      exclusion criteria were the association of predisposing factors (omphalocele,
      gastroschisis, diaphragmatic hernia). Patient characteristics, imaging
      investigations, operations performed, and morbidity were evaluated. RESULTS:
      Eleven children (7 boys and 4 girls) underwent a Ladd procedure at the median age
      of 14 days. Seven patients presented bilious vomiting, alimentary vomiting
      associated with weight loss (2 cases), and melena (1 patient) at admission. The
      upper gastrointestinal radiological investigations established the diagnosis of
      intestinal malrotation in 6 cases confirmed by ultrasonography in 3 cases.
      Isolated Doppler ultrasound investigation was sufficient in 4 cases before
      abdominal surgery. In 1 case, preoperative diagnosis of intestinal malrotation
      was not made. Intraoperative anomalies were midgut volvulus in 7 cases, Ladd
      bands in 3 patients, and malrotation with intestinal ischemia in 2 cases with
      spontaneous resolution of midgut volvulus. Incomplete intestinal malrotation (180
      degrees) was found in 10 cases and a mobile cecum in 1. CONCLUSION: These
      findings provide support for performing early diagnosis of intestinal malrotation
      to prevent the rare but potentially devastating complications of this anomaly.

PMID- 19097873
TI  - [Williams-Beuren syndrome: a multidisciplinary approach].
AB  - Williams-Beuren syndrome (WBS) (OMIM# 194050) is a rare, most often sporadic,
      genetic disease caused by a chromosomal microdeletion at locus 7q11.23 involving
      28 genes. Among these, the elastin gene codes for the essential component of the
      arterial extracellular matrix. Developmental disorders usually associate an
      atypical face, cardiovascular malformations (most often supravalvular aortic
      stenosis and/or pulmonary artery stenosis) and a unique neuropsychological
      profile. This profile is defined by moderate mental retardation, relatively well
      preserved language skills, visuospatial deficits and hypersociability. Other less
      known or rarer features, such as neonatal hypercalcemia, nutrition problems in
      infancy, ophthalmological anomalies, hypothyroidism, growth retardation, joint
      disturbances, dental anomalies and hypertension arising in adolescence or
      adulthood, should be treated. The aim of this paper is to summarize the major
      points of WBS regarding: (i) the different genes involved in the deletion and
      their function, especially the elastin gene and recent reports of rare forms of
      partial WBS or of an opposite syndrome stemming from a microduplication of the
      7q11.23 locus, (ii) the clinical features in children and adults with a focus on
      cardiovascular injury, and (iii) the specific neuropsychological profile of
      people with WBS through its characteristics, the brain structures involved, and
      learning.

PMID- 19097874
TI  - [Following the high-risk newborn: Why? How? Conducting an early medical
      psychosocial consultation during hospitalization].
AB  - The usual follow-up of high-risk children concentrates on screening for sequelae
      of perinatal pathology, required by emergency pediatricians and neonatologists to
      assess their practices. The objective is to manage pathologies by intervening as
      early as possible. However, is this classical medical model, i.e., the diagnosis
      of something pathological and a schedule of consultations planned at specific
      dates, adapted to the needs of high-risk children and their parents? Beyond
      screening, the child development consultation at the Rozanoff Early Medico-Social
      Action Center, set up at the A. Trousseau Hospital in 1985, proposes a
      consultation in which a neuropediatrician, a physical therapist, a pediatric
      psychiatrist-psychoanalyst, and a social worker closely collaborate. The care
      begun during neonatal hospitalization concentrates on the needs of the child and
      parents, with a primary objective of lending support to child-parent interaction.
      The observation of a child born at 26 GW presenting gaze avoidance concurrent
      with symptoms of depression in the mother exemplifies the importance of this
      visit. Why are there still so few of this type of consultation taking into
      account the medical, psychological, and social risks in a single visit? Why is
      the attention given to neurologic problems, for which there is currently no cure,
      so disproportionate to the lack of awareness of the psychological and social
      risks for which effective prevention and treatment possibilities do exist?

PMID- 19097875
TI  - Insulin resistance in chronic heart failure: a difficult bull to take by the
      horns.

PMID- 19097876
TI  - Response of juvenile scalloped hammerhead sharks to electric stimuli.
AB  - Sharks can use their electrosensory system to detect electric fields in their
      environment. Measurements of their electrosensitivity are often derived by
      calculating the voltage gradient from a model of the charge distribution for an
      ideal dipole. This study measures the charge distribution around a dipole in
      seawater and confirms the close correspondence with the model. From this, it is
      possible to predict how the sharks will respond to dipolar electric fields
      comprised of differing parameters. We tested these predictions by exposing sharks
      to different sized dipoles and levels of applied current that simulated the
      bioelectric fields of their natural prey items. The sharks initiated responses
      from a significantly greater distance with larger dipole sizes and also from a
      significantly greater distance with increasing levels of electric current. This
      study is the first to provide empirical evidence supporting a popular theoretical
      model and test predictions about how sharks will respond to a variety of
      different electric stimuli.

PMID- 19097877
TI  - Echocardiography and brain natriuretic peptide as prognostic indicators in
      idiopathic pulmonary fibrosis.
AB  - BACKGROUND: Pulmonary hypertension (PH) in idiopathic pulmonary fibrosis (IPF) is
      associated with poor prognosis. Recently echocardiography and brain natriuretic
      peptide (BNP) have been used as non-invasive markers for PH suggesting that they
      may also be used as markers for survival. The aim of this study was to evaluate
      the clinical usefulness of echocardiography and BNP by analyzing their
      association with survival. METHODS: Retrospective review of 131 patients with IPF
      who underwent both echocardiography and BNP measurement at a tertiary referral
      center. RESULTS: Mean follow-up period was 10.1 months. Using systolic pulmonary
      arterial pressure of 40 mmHg as a threshold for PH, patients with PH had poor
      survival (1-year mortality rate: 61.2%, mean survival: 10.8 months) than those
      without PH (19.9%, 23.7 months; p<0.001). The prognosis of the subjects with
      increased BNP levels was poorer than those with normal BNP levels (1-year
      mortality rate: 70.5% vs. 23.7%, mean survival: 11.0 months vs. 22.5 months;
      p<0.001) and on multivariate analysis, only BNP level was an independent
      predictor of prognosis. On serial evaluation, the survival of patients with newly
      developed PH and/or elevated BNP levels was similar to that of patients with PH
      at the initial measurement, suggesting that development of PH is indicative of
      poor prognosis regardless of the timing of the test. CONCLUSIONS: Although both
      BNP level and PH by echocardiography are clinically useful non-invasive and
      easily repeatable markers of prognosis, BNP level seems to be better.

PMID- 19097879
TI  - The Chartherm process, what's in the name?
AB  - Earlier research has identified the Chartherm process (Thermya, France) as a
      candidate for the best available technology to treat chromated copper arsenate
      (CCA) impregnated wood waste. This paper presents the working principle, the
      characteristics and the current state-of-knowledge related to the process,
      illustrating clearly the differences with pyrolysis and carbonisation processes.
      To emphasise the specific nature of the process, it has been given its own name
      'chartherisation'. The avoidance of tar and dioxin release, the role of the solid
      matrix in the metal behaviour and the separation process are described.
      Furthermore, the possible benefits of working at elevated pressure are discussed,
      based on the experience with charcoal production from coal and biomass. This
      paper shows that more fundamental research is needed to understand and model all
      mechanisms contributing to the characteristic nature of chartherisation, in order
      to control the dynamic behaviour and tune the operating conditions in the reactor
      on the quality of the products requested.

PMID- 19097880
TI  - A sensitive immunochromatographic assay using colloidal gold-antibody probe for
      rapid detection of pharmaceutical indomethacin in water samples.
AB  - One-step membrane-based competitive immunochromatographic assay using colloidal
      gold-antibody probe for rapid detection of indomethacin (IDM) in water samples
      was developed. A positive reaction as a result of the remaining gold-antibody
      conjugate combining with antigen coated on the membrane was obvious by visual
      detection. Under optimal conditions, the visual detection limit was found to be
      0.1 ngmL(-1), which was about 10-1000 times lower than those in published
      literatures, demonstrating the high sensitivity of the assay. The stability test
      indicated the immunochromatographic strips could be used for 8 weeks at room
      temperature without significant loss of activity. Real water samples were
      detected by the assay and confirmed by enzyme-linked immunosorbent assay. The
      assay time for indomethacin detection was less than 10 min, suitable for rapid
      testing on-site.

PMID- 19097881
TI  - Adjuvant 5-FU based chemotherapy for colon cancer: match or miss the mismatch?

PMID- 19097882
TI  - The European Organisation for Research and Treatment of Cancer Quality of Life
      Questionnaire for patients with bone metastases: the EORTC QLQ-BM22.
AB  - AIM: The aim of this study was to develop a bone metastases module to supplement
      the European Organisation for Research and Treatment of Cancer Core Questionnaire
      (EORTC QLQ-C30) or the EORTC QLQ-C15-PAL for patients with bone metastases.
      METHODS: Phases 1-2 of module development were conducted in Canada, Australia and
      Germany according to EORTC QOL group guidelines. Phase 3 was conducted in nine
      countries in seven languages. RESULTS: Sixty-one health-related quality of life
      (HRQOL) issues were generated from health care professionals (n=152) and patients
      (n=413). This resulted in a 22-item provisional module. Further testing in 170
      patients from nine countries resulted in the EORTC QLQ-BM22 module, containing 22
      items, conceptualised into both symptom scales, with five painful sites and three
      pain characteristics, and also functional scales, with eight functional
      interference and six psychosocial aspects. CONCLUSION: This study provides a
      provisional comprehensive HRQOL measurement tool for future trials, which will
      continue to undergo further validation.

PMID- 19097883
TI  - Herceptin and breast cancer: an overview for surgeons.
AB  - INTRODUCTION: HER-2 over-expression is implicated in the pathogenesis of breast
      cancer and represents a key marker and determinant of patient outcome.
      Trastuzumab/Herceptin (TZ) is a recombinant humanised monoclonal antibody which
      targets HER-2. Introduction into clinical practice has significantly improved the
      natural history of HER-2 over-expressing tumors and has altered the standard of
      care for these women. This article reviews the established and emerging roles of
      TZ in the management of breast cancer (BC). METHODS: Literature review
      facilitated by Medline and PubMed databases. FINDINGS: The clinical utility of TZ
      was first established in the management of HER-2 over-expressing metastatic
      breast cancer (MBC), with improvements recognised in both the quality and
      quantity of life. Prospective randomized controlled trials have consistently
      demonstrated the efficacy of TZ for early breast cancer (EBC) in the adjuvant
      setting with significant improvements in disease free and overall survival.
      Emerging roles for TZ include neo-adjuvant therapy and the treatment of
      progressive disease. TZ is well tolerated and safe, however, associated cardiac
      dysfunction remains a significant clinical concern. CONCLUSION: HER-2 status is
      critically important in the management algorithm for BC and should be determined
      in all cases. Quality assurance of laboratory testing is of paramount importance.
      TZ has an established role in the management of HER-2 positive MBC and EBC in
      conjunction with conventional chemotherapy. Appropriate patient selection and
      monitoring for cardiac dysfunction are required.

PMID- 19097884
TI  - Characterization of catechol derivative removal by lignin peroxidase in aqueous
      mixture.
AB  - The use of lignin peroxidase (LIP) as an alternative method for the removal of
      four catechols (1,2-dihydroxybenzene): catechol (CAT), 4-chlorocatechol (4-CC),
      4,5-dichlorocatechol (4,5-DCC) and 4-methylcatechol (4-MC) typical pollutants in
      wastewater derived from oil and paper industries, was evaluated. The removal of
      2mM catecholic substrates by 1 microM LIP after 1h was in the following order:
      4,5-DCC (95%)>4-CC(90%)>CAT(55%)>4-MC(43%). Except for 4-MC, all reactions were
      accompanied by the formation of insoluble products, leading to LIP precipitation.
      LIP was exposed to soluble or insoluble product-dependent inactivation, depending
      on the substrates tested, immediately at the start of the reactions. Despite
      immediate enzyme inactivation, removal of catecholic substrates continued,
      resulting in oligomeric product formation. Major oxidation products analyzed were
      compatible with dimeric, trimeric and tetrameric structures. Ether linkages and a
      benzoquinone structure were detected in two purified oligochlorocatechols.
      Catechol derivatives removal initiated by LIP, seems to be different for each
      catecholic substrate in terms of substrate consumption and transformation, and of
      enzyme activity.

PMID- 19097885
TI  - A comprehensive study on removal and recovery of copper(II) from aqueous
      solutions by NaOH-pretreated Marrubium globosum ssp. globosum leaves powder:
      potential for utilizing the copper(II) condensed desorption solutions in
      agricultural applications.
AB  - This paper reports on removal and recovery of copper(II) ions from aqueous
      solutions under batch experimental conditions using NaOH-pretreated powdered
      leaves of Marrubium globosum ssp. globosum plant. Experimental results showed
      that pH was optimized at the value of 5.5 by 16.23 mg/g. The increasing metal
      concentration and temperature caused an increase in biosorption capacity and the
      process reached its equilibrium in 60 min. The result obtained from kinetic and
      isotherm studies resulted in better agreement with pseudo second-order kinetic
      and Langmuir isotherm models. Thermodynamic parameters revealed that the Cu(2+)
      biosorption by the biomass was an endothermic process. The higher desorption
      efficiency above 90% was obtained in case of using Na(2)EDTA, K(4)O(7)P(2),
      HNO(3), HCl, and (NH(4))(2)C(2)O(4) x H(2)O solutions, individually. Reusability
      of the biomass was examined under consecutive biosorption-desorption cycles
      repeating five times. The most interesting finding of the study is the idea of
      utilizing the EDTA-Cu complex, which can be qualified as a residual from
      desorption processes, as a liquid chemical fertilizer in agricultural
      applications.

PMID- 19097886
TI  - Anammox for ammonia removal from pig manure effluents: effect of organic matter
      content on process performance.
AB  - The anammox process, under different organic loading rates (COD), was evaluated
      using a semi-continuous UASB reactor at 37 degrees C. Three different substrates
      were used: initially, synthetic wastewater, and later, two different pig manure
      effluents (after UASB-post-digestion and after partial oxidation) diluted with
      synthetic wastewater. High ammonium removal was achieved, up to 92.1+/-4.9% for
      diluted UASB-post-digested effluent (95 mg COD L(-1)) and up to 98.5+/-0.8% for
      diluted partially oxidized effluent (121 mg COD L(-1)). Mass balance clearly
      showed that an increase in organic loading (from 95 mg COD L(-1) to 237 mg COD L(
      1) and from 121 mg COD L(-1) to 290 mg COD L(-1) for the UASB-post-digested
      effluent and the partially oxidized effluent, respectively) negatively affected
      the anammox process and facilitated heterotrophic denitrification. Partial
      oxidation as a pre-treatment method improved ammonium removal at high organic
      matter concentration. Up to threshold organic load concentration of 142 mg COD L(
      1) of UASB-post-digested effluent and 242 mg COD L(-1) of partially oxidized
      effluent, no effect of organic loading on ammonia removal was registered
      (ammonium removal was above 80%). However, COD concentrations above 237 mg L(-1)
      (loading rate of 112 mg COD L(-1)day(-1)) for post-digested effluent and above
      290 mg L(-1) (loading rate of 136 mg COD L(-1)day(-1)) for partially oxidized
      effluent resulted in complete cease of ammonium removal. Results obtained showed
      that, denitrification and anammox process were simultaneously occurring in the
      reactor. Denitrification became the dominant ammonium removal process when the
      COD loading was increased.

PMID- 19097887
TI  - Flocculation characteristics of an isolated mutant flocculent Saccharomyces
      cerevisiae strain and its application for fuel ethanol production from kitchen
      refuse.
AB  - A stable mutant flocculent yeast strain of Saccharomyces cerevisiae KRM-1 was
      isolated during repeated-batch ethanol fermentation using kitchen refuse as the
      medium. The mechanism of flocculation and interaction with the medium was
      investigated. According to sugar inhibition assay, it was found that the mutant
      flocculent strain was a NewFlo phenotype. Flocculation was completely inhibited
      by protease, proteinase K and partially reduced by treatments with carbohydrate
      hydrolyzing enzymes. Flocculation ability showed no difference for pH 3.0-6.0.
      Furthermore, the mutant flocculent yeast provided repeated-batch cultivations
      employing cell recycles by flocculation over 10 rounds of cultivation for the
      production of ethanol from kitchen refuse medium, resulting in relatively high
      productivity averaging 8.25 g/L/h over 10 batches and with a maximal of 10.08
      g/L/h in the final batch. Cell recycle by flocculation was fast and convenient,
      and could therefore be applicable for industrial-scale ethanol production.

PMID- 19097888
TI  - Synthesis and CB1 cannabinoid receptor affinity of 4-alkoxycarbonyl-1,5-diaryl
      1,2,3-triazoles.
AB  - A series of 4-alkoxycarbonyl-1,5-diaryl-1,2,3-triazoles were synthesized
      regioselectively using click chemistry and evaluated at CB1 cannabinoid
      receptors. The n-propyl ester 11 (K(i)=4.6 nM) and phenyl ester 14 (K(i)=11 nM)
      exhibited the most potent affinity of the series.

PMID- 19097889
TI  - Development of pH-responsive core-shell nanocarriers for delivery of therapeutic
      and diagnostic agents.
AB  - In this paper new dendritic core-shell architectures with pH-labile linkers based
      on hyperbranched polyglycerol cores and biocompatible poly(ethylene glycol)
      shells were synthesized which encapsulate the anticancer agent doxorubicin and a
      dye for near-infrared imaging, an indotricarbocyanine. Acid-sensitive properties
      of the new nanocarriers and in vitro cytotoxicity of the doxorubicin-nanocarrier
      are presented as well as preliminary data regarding their toxicity and tumor
      targeting potential in nude mice.

PMID- 19097890
TI  - (S)-N-(5-Chlorothiophene-2-sulfonyl)-beta,beta-diethylalaninol a Notch-1-sparing
      gamma-secretase inhibitor.
AB  - Accumulation of beta-amyloid (Abeta), produced by the proteolytic cleavage of
      amyloid precursor protein (APP) by beta- and gamma-secretase, is widely believed
      to be associated with Alzheimer's disease (AD). Research around the high
      throughput screening hit (S)-4-chlorophenylsulfonyl isoleucinol led to the
      identification of the Notch-1-sparing (9.5-fold) gamma-secretase inhibitor (S)-N
      (5-chlorothiophene-2-sulfonyl)-beta,beta-diethylalaninol 7.b.2 (Abeta(40/42)
      EC(50)=28 nM), which is efficacious in reduction of Abeta production in vivo.

PMID- 19097891
TI  - Structure-based hybridization of the bioactive natural products rhizonin A and
      ternatin leading to a selective fat-accumulation inhibitor against 3T3-L1
      adipocytes.
AB  - Based on the structural similarity between the naturally occurring cyclic
      heptapeptides rhizonin A and ternatin, two novel analogues were designed. The
      synthetic analogues were assessed with regard to their fat-accumulation
      inhibitory effect against 3T3-L1 adipocytes, and this led to the discovery of a
      potent and selective fat-accumulation inhibitor compared to the parent compound
      rhizonin A.

PMID- 19097892
TI  - Potent and selective inhibitors of Helicobacter pylori glutamate racemase (MurI):
      pyridodiazepine amines.
AB  - An SAR study of an HTS screening hit generated a series of pyridodiazepine amines
      as potent inhibitors of Helicobacter pylori glutamate racemase (MurI) showing
      highly selective anti-H. pylori activity, marked improved solubility, and reduced
      plasma protein binding. X-ray co-crystal E-I structures were obtained. These
      uncompetitive inhibitors bind at the MurI dimer interface.

PMID- 19097893
TI  - Positive allosteric modulators of the metabotropic glutamate receptor subtype 4
      (mGluR4). Part II: Challenges in hit-to-lead.
AB  - This Letter describes the synthesis and SAR of two mGluR4 positive allosteric
      modulator leads, 6 and 7. VU001171 (6) represents the most potent (EC(50)=650
      nM), efficacious (141% Glu Max) and largest fold shift (36-fold) of any mGluR4
      PAM reported to date. However, this work highlights the challenges in hit-to-lead
      for mGluR4 PAMs, with multiple confirmed HTS hits displaying little or no
      tractable SAR.

PMID- 19097894
TI  - Synthesis and antimicrobial activities of halogenated bis(hydroxyphenyl)methanes.
AB  - A series of halophenols was prepared by the reaction of
      bis(hydroxyphenyl)methanes with effective halogenating agents such as bromine and
      sulfuryl chloride. One of these compounds, a biologically active halophenol-
      2,2',3,3'-tetrabromo-4,4',5,5'-tetrahydroxydiphenylmethane (1)--frequently
      isolated from red algae, was synthesized for the first time. Other halophenols
      included several novel compounds, together with known derivatives that were
      synthesized from the phenolic intermediates, bis(3,4-dihydroxyphenyl)methane (5)
      and bis(2-hydroxyphenyl)methane (14). All of the synthesized compounds were
      tested for antimicrobial activity against Gram-positive, Gram-negative bacteria
      and fungi. The preliminary structure-activity relationship was investigated in
      order to determine the essential structural requirements for their antimicrobial
      activity. Of all these halophenols, 2,2',3,3',6-pentabromo-4,4',5,5'
      tetrahydroxydiphenylmethane (8) was found to be the most active against
      Candidaalbicans, Aspergillusfumigatus, Trichophytonrubrum, and
      Trichophytonmentagrophytes while 3,3',5,5'-tetrachloro-2,2'
      dihydroxydiphenylmethane (18) exerted a powerful antibacterial effect against
      Staphylococcusaureus, Bacillussubtilis, Micrococcusluteus, Proteusvulgaris, and
      Salmonellatyphimurium.

PMID- 19097895
TI  - Submicromolar phosphinic inhibitors of Escherichia coli aspartate
      transcarbamoylase.
AB  - The design, syntheses, and enzymatic activity of two submicromolar competitive
      inhibitors of aspartate transcarbamoylase (ATCase) are described. The phosphinate
      inhibitors are analogs of N-phosphonacetyl-l-aspartate (PALA) but have a reduced
      charge at the phosphorus moiety. The mechanistic implications are discussed in
      terms of a possible cyclic transition-state during enzymatic catalysis.

PMID- 19097896
TI  - 3-Aminoxypropionate-based linker system for cyclization activation in prodrug
      design.
AB  - A novel linker system based on 3-aminoxypropionate was designed and evaluated for
      drug release using proteolysis as an activation trigger followed by
      intramolecular cyclization. The hydroxylamine moiety present in the linker system
      enabled faster release of the parent drug from the linker-drug conjugate at lower
      pH as compared to an aliphatic amine moiety. Introduction of two methyl groups
      strategically at the alpha position to the carboxylate in the linker further
      improved the rate of cyclization by nearly 2-fold. The 3-aminoxypropionate linker
      was successfully applied to a model prodrug for protease activation using alpha
      chymotrypsin as the activating enzyme; the activation of the model prodrug
      bearing the 3-aminoxypropionate linker was 136 times faster than the
      corresponding model prodrug bearing an amine linker.

PMID- 19097897
TI  - 158th ENMC international workshop on congenital muscular dystrophy (Xth
      international CMD workshop) 8th-10th February 2008 Naarden, The Netherlands.

PMID- 19097898
TI  - Predator percolation, insect outbreaks, and phase polyphenism.
AB  - Apart from being notorious outbreak pests, locusts are of interest because of
      their expression of density-dependent "phase polyphenism." In this remarkable
      form of phenotypic plasticity, changes in local population density generate
      distinct solitarious and gregarious phases that differ in behavior, physiology,
      and appearance. A hallmark of phase polyphenism in outbreak species is the
      transition from solitary living to group formation and subsequent mass movement
      in migratory bands or swarms, yet there has been no convincing general
      explanation for the evolution of these density-dependent switches in spatial
      distribution. Using a model from "percolation theory", we show that it would be
      highly detrimental for locust individuals to continue indefinitely in a dispersed
      spatial distribution as their population densities increase. Switching to an
      extremely clumped distribution is advantageous because it disrupts the
      connectivity of predators' food-patch networks. Thus, selection pressure from
      predators has probably been an important factor underlying the initial evolution
      of conditional switches between "dispersed" and strongly aggregative behavior,
      which will also affect outbreak dynamics. Although group formation is the best
      alternative for high-density populations, it brings its own set of severe
      problems, resulting in secondary selection for many of the traits seen in
      gregarious-phase individuals.

PMID- 19097899
TI  - Face processing in the chimpanzee brain.
AB  - Human face recognition involves highly specialized cognitive and neural processes
      that enable the recognition of specific individuals. Although comparative studies
      suggest that similar cognitive processes underlie face recognition in chimpanzees
      and humans ([6-8] and Supplemental Data), it remains unknown whether chimpanzees
      also show face-selective activity in ventral temporal cortex. This study is the
      first to examine regional cerebral glucose metabolism with (18)F
      flurodeoxyglucose positron emission tomography in chimpanzees after they
      performed computerized tasks matching conspecifics' faces and nonface objects
      (Supplemental Data). A whole-brain analysis comparing these two tasks in five
      chimpanzees revealed significant face-selective activity in regions known to
      comprise the distributed cortical face-processing network in humans, including
      superior temporal sulcus and orbitofrontal cortex. In order to identify regions
      that were exclusively active during one task, but not the other, we subtracted a
      resting-state condition from each task and identified the activity exclusive to
      each. This revealed numerous distinct patches of face-selective activity in the
      fusiform gyrus that were interspersed within a large expanse of object-selective
      cortex. This pattern suggests similar object form topography in the ventral
      temporal cortex of chimpanzees and humans, in which faces may represent a special
      class of visual stimulus.

PMID- 19097900
TI  - Polycomb silencing of KNOX genes confines shoot stem cell niches in Arabidopsis.
AB  - Most plant organs develop postembryonically from stem cells in the shoot and root
      meristems. In Arabidopsis, Class I KNOTTED-like homeobox (KNOX) transcription
      factors are specifically expressed in shoot meristems and play a primary role in
      the maintenance of meristem function. Although suppression of KNOX was shown to
      associate with histone H3K27-methylation, the molecular mechanism underlying this
      suppression is not well understood. Here, we provide genetic, molecular, and
      functional evidence that an Arabidopsis POLYCOMB REPRESSIVE COMPLEX1 (PRC1)-like
      complex acts in conjunction with PRC2 in KNOX suppression. We identified AtRING1a
      and AtRING1b as homologs of the animal PRC1 core component RING1. Loss-of
      function mutant Atring1a(-/-)Atring1b(-/-) shows release of KNOX suppression and
      ectopic-meristem formation. AtRING1a and AtRING1b proteins are localized in the
      nucleus. AtRING1a binds to itself and to AtRING1b, to CURLY LEAF (CLF), a PRC2
      core component catalyzing H3K27-methylation, and to LIKE HETEROCHROMATIN PROTEIN1
      (LHP1), a chromodomain protein binding trimethyl-H3K27. We further show that clf(
      /-) and lhp1(-/-) enhance Atring1a(-/-)Atring1b(-/-) in release of KNOX
      suppression and mutant phenotypes. We propose a model in which AtRING1a,
      AtRING1b, and LHP1 form a PRC1-like complex, which binds trimethyl-H3K27 marked
      by the CLF-containing PRC2, resulting in transcriptional suppression of KNOX.

PMID- 19097901
TI  - Fruit-catching fish tune their fast starts to compensate for drift.
AB  - Numerous animal navigators are not simply at the mercy of winds and currents but
      cope with drift to reach their goals. Here, we report how a fruit-catching Costa
      Rican fish combines an analysis of aerial motion with a novel way of compensating
      for drift to optimize its catching success. In the field, schools of this
      riverine fish never waited until a falling fruit actually landed in the stream.
      Rather, the fish responded to visual motion and started early to arrive on time
      at the spot where their food would land. To be successful with their early
      starts, the fish must cope with the strong relative drift that arises, because
      the fish, but not their airborne target, experience strong flow on their way
      toward the fruit's landing point. Surprisingly, the fish solve this problem right
      at the beginning-by turning rapidly and taking an initial aim that is already
      optimally adapted to the prevailing drift, so as to lead them straight to their
      food. Fruit-catching fish thus provide a stunning case of how rapidly animals can
      generate drift-compensating trajectories in their everyday local lives.

PMID- 19097902
TI  - A feedback mechanism controlling SCRAMBLED receptor accumulation and cell-type
      pattern in Arabidopsis.
AB  - Cellular pattern formation in the root epidermis of Arabidopsis occurs in a
      position-dependent manner, generating root-hair (H) cells contacting two
      underlying cortical cells and nonhair (N) cells contacting one cortical cell.
      SCRAMBLED (SCM), a leucine-rich repeat receptor-like kinase (LRR-RLK), mediates
      this process through its effect on a downstream transcription factor regulatory
      network. After perception of a positional cue, the SCM signaling pathway is
      proposed to preferentially repress WEREWOLF (WER) transcription factor expression
      in H cells and thereby bias the outcome of mutual lateral inhibition acting
      between H and N cells. However, the molecular mechanism responsible for this
      preferential SCM signaling is unknown. Here, we analyze the distribution of the
      SCM receptor and the biological effect of altering its accumulation pattern. We
      find that SCM expression and accumulation in the epidermal cell layer is
      necessary and sufficient to direct the cell-type pattern. Further, SCM
      preferentially accumulates in H cells, and this accumulation pattern is dependent
      on the downstream transcription factors. Thus, SCM participates in an
      autoregulatory feedback loop, enabling cells engaged in SCM signaling to maintain
      high levels of SCM receptor, which provides a simple mechanism for reinforcing a
      bias in receptor-mediated signaling to ensure robust pattern formation.

PMID- 19097903
TI  - Arabidopsis phyllotaxis is controlled by the methyl-esterification status of cell
      wall pectins.
AB  - Plant organs are produced from meristems in a characteristic pattern. This
      pattern, referred to as phyllotaxis, is thought to be generated by local
      gradients of an information molecule, auxin. Some studies propose a key role for
      the mechanical properties of the cell walls in the control of organ outgrowth. A
      major cell-wall component is the linear alpha-1-4-linked D-GalAp pectic
      polysaccharide homogalacturonan (HG), which plays a key role in cell-to-cell
      cohesion. HG is deposited in the cell wall in a highly (70%-80%) methyl
      esterified form and is subsequently de-methyl-esterified by pectin methyl
      esterases (PME, EC 3.1.1.11). PME activity is itself regulated by endogenous PME
      inhibitor (PMEI) proteins. PME action modulates cell-wall-matrix properties and
      plays a role in the control of cell growth. Here, we show that the formation of
      flower primordia in the Arabidopsis shoot apical meristem is accompanied by the
      de-methyl-esterification of pectic polysaccharides in the cell walls. In
      addition, experimental perturbation of the methyl-esterification status of
      pectins within the meristem dramatically alters the phyllotactic pattern. These
      results demonstrate that regulated de-methyl-esterification of pectins is a key
      event in the outgrowth of primordia and possibly also in phyllotactic patterning.

PMID- 19097905
TI  - Relationship of gliomas to the ventricular walls.
AB  - The role of neural stem cells in gliomagenesis remains controversial. The aim of
      this study was to determine the anatomic relationship of human gliomas to the
      lining of the ventricular walls, known as the subventricular zone, an area
      replete with neural stem cells. We performed a retrospective radiographic
      analysis of 100 consecutive patients with gliomas and sought to determine the
      relationship of the lesions to the ventricular walls as seen on their MRI scans.
      Our results indicated that in 93% of cases the lesions contacted at least one
      region of the lateral ventricular wall. Contact with the ventricular wall was
      independent of the glioma size or mass effect. These findings were correlated to
      cytoarchitectural studies of the human subventricular zone. Our findings lend
      further support that there is an intimate association between gliomas and the
      subventricular zone.

PMID- 19097904
TI  - An IFT-A protein is required to delimit functionally distinct zones in
      mechanosensory cilia.
AB  - BACKGROUND: Conserved intraflagellar transport (IFT) particle proteins and IFT
      associated motors are needed to assemble most eukaryotic cilia and flagella.
      Proteins in an IFT-A subcomplex are generally required for dynein-driven
      retrograde IFT, from the ciliary tip to the base. We describe novel structural
      and functional roles for IFT-A proteins in chordotonal organs, insect
      mechanosensory organs with cilia that are both sensory and motile. RESULTS: The
      reduced mechanoreceptor potential A (rempA) locus of Drosophila encodes the IFT-A
      component IFT140. Chordotonal cilia are shortened in rempA mutants and an IFT-B
      protein accumulates in the mutant cilia, consistent with a defect in retrograde
      IFT. A functional REMPA-YFP fusion protein concentrates at the site of the
      ciliary dilation (CD), a highly structured axonemal inclusion of hitherto unknown
      composition and function. The CD is absent in rempA mutants, and REMPA-YFP is
      undetectable in the absence of another IFT-A protein, IFT122. In a mutant lacking
      the IFT dynein motor, the CD is disorganized and REMPA-YFP is mislocalized. A
      TRPV ion channel, required to generate sensory potentials and regulate ciliary
      motility, is normally localized in the cilia, proximal to the CD. This channel
      spreads into the distal part of the cilia in dynein mutants and is undetectable
      in rempA mutants. CONCLUSIONS: IFT-A proteins are located at and required by the
      ciliary dilation, which separates chordotonal cilia into functionally distinct
      zones. A requirement for IFT140 in stable TRPV channel expression also suggests
      that IFT-A proteins may mediate preciliary transport of some membrane proteins.

PMID- 19097906
TI  - Pituitary insufficiency after traumatic brain injury.
AB  - After traumatic brain injury (TBI), patients present with psychological disorders
      that may be explained by post-traumatic pituitary insufficiency (PI). The goal of
      this study was to determine the relationship between hypopituitarism,
      neuropsychological changes and findings on CT scans after TBI. Hospital charts of
      55 TBI patients were screened for age, Glasgow Coma Scale (GSC) score, hypoxia or
      hypotension. The first two CT scans were analyzed for hemorrhagic lesions. Basal
      levels of the following hormones were recorded: cortisol, prolactin, estradiol,
      testosterone, insulin-like growth factor 1 and free thyroxine. Hormonal
      stimulation tests were performed either if the basal hormone screening revealed
      an abnormality or if the patient answered "yes" to at least one question in the
      non-evaluated neuropsychological questionnaire. Overall, 14 out of 55 patients
      (25.4%) presented with PI; one of them with two hormonal deficits. Growth hormone
      deficit, hypothyroidism and hypocortisolism were found in one, one and two
      patients, respectively. Neuropsychological complaints were present in 67% of the
      patients and were associated with intracerebral hemorrhagic lesions and not PI.
      Neuropsychological complaints after TBI are more frequent than PI. Brain tissue
      damage is most important than PI in the development of psychological changes
      after TBI.

PMID- 19097907
TI  - STA-MCA bypass for symptomatic carotid occlusion and haemodynamic impairment.
AB  - Patients with carotid artery occlusion and haemodynamic insufficiency have a high
      risk of stroke. Cerebral revascularization surgery improves cerebral blood flow,
      but it remains unclear whether this reduces the risk of stroke. This study
      assesses the long-term outcome of patients undergoing superficial temporal artery
      to middle cerebral artery (STA-MCA) bypass for symptomatic carotid occlusion. The
      long-term clinical follow-up and haemodynamic reserve, measured by (99)Technetium
      single photon emission computed tomography (Tc99 SPECT) scan with acetazolamide
      challenge, were reviewed for 19 consecutive patients before and after STA-MCA
      bypass. The stroke rate after bypass surgery was 8% per year. In patients waiting
      for surgery, the stroke rate was 18% per year. Cerebral perfusion assessed with
      SPECT scan improved in 88% of patients. These results are consistent with the
      high risks of haemodynamic infarction in untreated patients and a benefit from
      revascularization surgery. The percentage annual stroke risk compares favourably
      with an 18% rate reported for patients with internal carotid artery occlusion and
      impaired cerebrovascular reserve.

PMID- 19097908
TI  - Novel polymorphisms of the amyloid precursor protein (APP) gene in
      Chinese/Taiwanese patients with Alzheimer's disease.
AB  - We aimed to determine if the amyloid precursor protein (APP) gene polymorphism is
      present in Chinese/Taiwanese patients with Alzheimer's disease (AD). This is a 3
      year prospective assessment of the genotypes of the APP gene among
      Chinese/Taiwanese patients with AD. The sample consisted of 50 AD patients and 50
      unaffected controls. Participants were recruited from the practices of the
      authors. Controls were comprised of 45 unrelated healthy subjects and 5
      unaffected family members of AD patients. Data were collected in a university
      based research unit of a tertiary medical center. Sequencing of the APP gene from
      exon 15 to exon 18 was performed on the peripheral blood of the patients and the
      unaffected controls after their informed consent was obtained. Among 50 AD
      subjects, 11 (7 men, 4 women) had APP gene polymorphisms. Mean age of onset was
      72 years (range 65-82 years). Polymorphism of APP gene with A to C substitution
      at nucleotide position (nt) 284490 (A284490C) was found in 8 AD patients, at nt
      284493 (A284493C) in 5, T284497C in 3 patients, and T284500C in 1 patient. These
      single nucleotide substitutions of the APP gene corresponded to the amino acid
      substitutions I718L, L720S, and V710G. These polymorphisms were not found in the
      unaffected controls. The mutations were confirmed by StyI restriction enzyme
      digestion assay using the subclone from polymerase chain reaction (PCR) products
      of the mutated APP gene. Thus, APP gene polymorphisms at codon 718 (I>L), 720
      (L>S), and 710 (V>G) can be found in certain Chinese/Taiwanese patients with
      Alzheimer's disease.

PMID- 19097909
TI  - Imaging the penumbra - strategies to detect tissue at risk after ischemic stroke.
AB  - The aim of thrombolytic therapy after acute ischemic stroke is salvage of the
      ischemic penumbra. Several imaging techniques have been used to identify the
      penumbra in patients who may benefit from reperfusion beyond the currently narrow
      3-hour time-window for thrombolysis. We discuss the advantages and disadvantages
      of positron emission tomography (PET), single photon emission computed tomography
      (SPECT), MRI and CT scans. We comment on concepts of clinical-imaging mismatch
      models and we explore the implications for clinical trials.

PMID- 19097910
TI  - Cemented versus uncemented fixation of the femoral component of the NexGen CR
      total knee replacement in patients younger than 60 years: a prospective
      randomised controlled RSA study.
AB  - The optimal mode of femoral fixation in total knee arthroplasty (TKA) remains
      controversial, especially for the young patient. In a prospective randomised
      study we compared the magnitude and pattern of the fixation of cemented versus
      uncemented femoral components during 2 years in patients younger than 60 years.
      Forty-one knees in 41 patients were randomised to receive a NexGen (Zimmer,
      Warsaw, USA) cruciate-retaining TKA with either a cemented or an uncemented non
      HA-coated femoral component. The patients were examined by radiostereometric
      analysis (RSA), as well as clinical and radiological evaluation. The magnitude
      and pattern of migration as measured by RSA did not differ significantly between
      the cemented and uncemented fixation during the 2-year follow-up, nor were there
      any differences between the groups in clinical parameters. These findings suggest
      that an uncemented and non HA-coated femoral component may behave equally as well
      as a cemented one in the long-term.

PMID- 19097911
TI  - Ligand-based and structure-based virtual screening to identify carbonic anhydrase
      IX inhibitors.
AB  - A three-dimensional pharmacophore model of CA IX inhibitors was generated and
      used to screen the ZINC database of commercially available compounds. The hits
      were docked in a CA IX homology model. By visualizing the binding mode and score
      of these compounds, six derivatives were selected and evaluated for their
      inhibitory potency against CA IX. A highly active CA IX inhibitor was identified
      which may be used as a lead to design novel such derivatives.

PMID- 19097912
TI  - DNA photocleavage by porphyrin-polyamine conjugates.
AB  - A series of polyamine-porphyrin conjugates bearing two (cis or trans position) or
      four units of spermidine or spermine was synthesized. We studied the binding of
      these cationic porphyrins to calf thymus DNA by the means of UV-vis spectroscopy
      and we investigated their ability to cleave plasmid DNA in the presence of light.
      DNA binding and DNA photocleavage abilities were found to depend on structural
      characteristics as (a) the relative positions of the side chains on the porphyrin
      ring and (b) the nature of the attached side chains (spermidine or spermine). DNA
      cleavage was also studied in the presence of a singlet oxygen quencher (NaN(3))
      and in the presence of a hydroxyl radical scavenger (mannitol). Singlet oxygen
      was the major species responsible for the cleavage of DNA previously observed.
      Collectively, these data show that polyamine-porphyrin conjugates could be
      promising phototherapeutic agents.

PMID- 19097913
TI  - DNA binding, cytotoxicity, apoptotic inducing activity, and molecular modeling
      study of quercetin zinc(II) complex.
AB  - DNA cleavage activity of quercetin zinc(II) complex has been studied, but little
      attention has been devoted to the relationship between antitumor activity of this
      complex and DNA-binding properties. DNA-binding properties of quercetin zinc(II)
      complex were studied using UV-vis spectra, fluorescence measurements, and
      viscosity measurements. The results obtained indicate that quercetin zinc(II)
      complex can intercalate into the stacked base pairs of DNA, and compete with the
      strong intercalator ethidium bromide for the intercalative binding sites with
      Stern-Volmer quenching constant, K(sq)=1.24. The complex was subjected to
      biological tests in vitro using three tumor cell lines (HepG2, SMMC7721, and
      A549), which showed significant cytotoxicity against three tumor cell lines.
      Moreover, Hoechst33258 staining showed HepG2 cells underwent the typical
      morphologic changes of apoptosis characterized by nuclear shrinkage, chromatin
      condensation, or fragmentation after exposure to the complex. In addition,
      Molecular modeling was performed to learn the complex could be preferentially
      bound to DNA in GC region. Our results suggest that antitumor activity of
      quercetin zinc(II) complex might be related to its intercalation into DNA.

PMID- 19097914
TI  - Synthesis and antibacterial property of quinolines with potent DNA gyrase
      activity.
AB  - Synthesis of a series of novel tetrahydroquinoline annulated heterocycles has
      been accomplished by intramolecular imino and bisimino Diels-Alder reaction.
      These compounds were evaluated for their antibacterial activity. All the
      synthetic compounds, exhibited good antibacterial activity against microorganisms
      of which one of them 7 was found to be as active as the antibiotic ciplofloxacin
      and is found to have MIC value of 2.5 mg/mL against Escherichia coli.

PMID- 19097915
TI  - Kisspeptins and GnRH neuronal signalling.
AB  - Kisspeptin binding to its G-protein-coupled receptor KISS1R (also known as
      GPR54), which is expressed by gonadotropin-releasing hormone (GnRH) neurons,
      stimulates GnRH release and activation of the mammalian reproductive axis.
      Kisspeptin neurons make close contact with GnRH neurons acting at both the cell
      body and the nerve terminals. Kisspeptin can act directly on GnRH neurons and/or
      indirectly via synaptic input from other neurons to inhibit inwardly rectifying
      potassium channels and activate non-specific cation channels, with the effect of
      long-lasting depolarization and increased action potential firing rate. This
      review covers the recent advances in the molecular consequences of kisspeptin
      action on GnRH neurons and how these neuronal circuits are integrated in
      different species. These studies provide insight into the mechanism by which
      kisspeptin regulates the reproductive axis.

PMID- 19097916
TI  - The effect of repeated endurance exercise on IL-6 and sIL-6R and their
      relationship with sensations of fatigue at rest.
AB  - Strenuous, prolonged exercise increases interleukin-6 (IL-6) release. The effect
      of IL-6 is dependent on the availability of IL-6 receptors. Few studies have
      addressed the impact of exercise on IL-6 receptor levels or procalcitonin (PCT),
      an indicator of systemic inflammation. Changes in these molecules may give
      insight into cytokine-related mechanisms underlying exercise-related fatigue.
      Thirteen trained male subjects partook in the study. They cycled a total distance
      of 468 km over 6 days. Blood samples were obtained prior to and immediately
      following Day 1 of the study and then each morning prior to exercise. Blood
      samples were analysed for plasma IL-6, soluble IL-6 receptor (sIL-6R), C-reactive
      protein (CRP), PCT, creatine kinase (CK) and cortisol concentrations. Subjects
      also completed mood state questionnaires each day prior to exercise. IL-6 was
      elevated immediately post-exercise on Day 1 but was unchanged at rest for the
      duration of the event. In contrast, sIL-6R, CRP, PCT and CK concentrations were
      unchanged immediately post-exercise on Day 1 but were significantly elevated at
      rest over the duration of the event compared with pre-event baseline. sIL-6R was
      highly correlated to CRP. Cortisol concentrations remained unchanged at all time
      points. In conclusion, strenuous, prolonged exercise stimulated an acute phase
      response which was maintained throughout the 6-day event. sIL-6R increase is
      associated with CRP and may affect subjective sensations of post-exercise fatigue
      at rest.

PMID- 19097917
TI  - EMG activity of hip and trunk muscles during deep-water running.
AB  - The present study used synchronized motion analysis to investigate the activity
      of hip and trunk muscles during deep-water running (DWR) relative to land walking
      (LW) and water walking (WW). Nine healthy men performed each exercise at self
      determined slow, moderate, and fast paces, and surface electromyography was used
      to investigate activity of the adductor longus, gluteus maxima, gluteus medius,
      rectus abdominis, oblique externus abdominis, and erector spinae. The following
      kinematic parameters were calculated: the duration of one cycle, range of motion
      (ROM) of the hip joint, and absolute angles of the pelvis and trunk with respect
      to the vertical axis in the sagittal plane. The percentages of maximal voluntary
      contraction (%MVC) of each muscle were higher during DWR than during LW and WW.
      The %MVC of the erector spinae during WW increased concomitant with the pace
      increment. The hip joint ROMs were larger in DWR than in LW and WW. Forward
      inclinations of the trunk were apparent for DWR and fast-paced WW. The pelvis was
      inclined forward in DWR and WW. In conclusion, the higher-level activities during
      DWR are affected by greater hip joint motion and body inclinations with an
      unstable floating situation.

PMID- 19097918
TI  - TIPS: comparison of shunt patency and clinical outcomes between bare stents and
      expanded polytetrafluoroethylene stent-grafts.
AB  - PURPOSE: To compare shunt patency and clinical outcomes in two groups of patients
      who received a transjugular intrahepatic portosystemic shunt (TIPS): one group
      with bare stents and one with expanded polytetrafluoroethylene stent-grafts.
      MATERIALS AND METHODS: TIPS were created with bare stents (n = 41) or stent
      grafts (n = 40). Overall TIPS patency rates were compared between these two
      groups, as were clinical outcomes in patients with variceal bleeding and those
      with ascites. RESULTS: In the bare stent group, primary shunt patency rates were
      63%, 48%, and 24% at 3, 6, and 12 months, respectively. Secondary patency rates
      were 75% and 62% at 3 and 6 months, respectively. In the stent-graft group,
      primary patency rates were 94%, 67%, and 38% at 3, 6, and 12 months,
      respectively. Secondary patency rates were 100% and 92% at 3 and 6 months,
      respectively. All stent patency rates were higher in the stent-graft group, but
      only the difference in the 3-month primary patency rate (63% vs 94%) reached
      significance (P = .03). In patients with variceal bleeding as well as those with
      ascites, early and overall clinical success rates were higher in the stent-graft
      group, but only the 3-month and 12-month differences were statistically
      significant. CONCLUSIONS: TIPS created with stent-grafts had better 3-month
      primary patency rates and better 3-month and 12-month clinical success rates
      compared with those created with bare stents.

PMID- 19097920
TI  - Juvenile galactosialidosis with attacks of neuropathic pain and absence of
      sialyloligosacchariduria.
AB  - Galactosialidosis (MIM 256540) is an autosomal recessive lysosomal storage
      disease caused by a defect of the protective protein/cathepsin A. Increased
      amounts of urinary sialic acid-rich oligosaccharides are considered to be an
      essential diagnostic marker of the disease. We here report a patient with
      atypical clinical features who consistently has excreted normal amounts of
      sialyloligosaccharides in the urine. The boy started to have attacks of
      neuropathic pain associated with hyperesthesia around 1(1/2) years of age. From 4
      years of age when his vision was first tested, the patient developed progressive
      visual loss and at the age of 10 years, macular cherry-red spots were found. At
      this age, he also had a mild learning disability and clinical examination showed
      mild facial coarsening, increased lumbar lordosis and pyramidal signs in the
      legs. In conclusion, the clinical and laboratory features of this patient show
      that galactosialidosis may be considered in patients even in the absence of
      oligosacchariduria and that galactosialidosis should be regarded as a
      differential diagnosis in patients with neuropathic pain.

PMID- 19097919
TI  - Strong association of MRI meniscal derangement and bone marrow lesions in knee
      osteoarthritis: data from the osteoarthritis initiative.
AB  - INTRODUCTION: Meniscal damage is common in knee Osteoarthritis (OA) and
      predictive of structural progression, suggesting that their disruption plays a
      role in the development of OA. The bone marrow lesion (BML) is associated with
      pain and is a strong risk factor for structural progression. These lesions are
      associated with abnormal loading in a knee joint. Therefore, our hypothesis was
      that in those with symptomatic knee OA, large BMLs would be associated with ipsi
      compartmental meniscal derangement. METHODS: This was a cross-sectional study of
      a subsample of the Osteoarthritis Initiative where one set of magnetic resonance
      (MR) images from each participant was scored for tibiofemoral BMLs and meniscal
      derangement. We performed chi-squared tests comparing the prevalence of large
      BMLs in those with ipsi-compartmental meniscal derangement and those without.
      RESULTS: 160 Participants had a mean age of 61 (+/-9.9), mean BMI of 30.3 (+/
      4.7) and 50% were female. 79% of medial and 39% of lateral menisci showed MRI
      (Magnetic Resonance Imaging) derangement. In those with medial meniscal MRI
      derangement, 44% had large medial BMLs while in those without medial meniscal
      derangement, 0% had large BMLs. Similar results were seen in the lateral
      compartment. CONCLUSION: Medial and lateral MRI meniscal derangement are highly
      prevalent in symptomatic knee OA and BMLs are highly associated with ipsi
      compartmental MRI meniscal derangement.

PMID- 19097921
TI  - In obese and non-obese adults, the cis-regulatory rs361072 promoter variant of
      PIK3CB is associated with insulin resistance not with type 2 diabetes.
AB  - We recently reported that rs361072, a promoter C/T variant of p110beta, the
      catalytic subunit of PI3-kinase, was associated with a protection from insulin
      resistance (IR) in Caucasian adolescents in proportion of their body mass. We
      tested if this cis-regulatory QTL is associated with IR and type 2 diabetes in
      7885 middle-aged obese and non-obese adults of European ancestry. We genotyped
      rs361072 in 1139 non-diabetic obese (NDO) European adults, in whom IR was
      estimated by the HOMA-IR index. We also studied 427 type 2 diabetic obese adults
      (DO) and 424 diabetic non-obese (DNO) adults to test whether their disease status
      was associated with a decreased prevalence of the protective variant. The
      prevalence of rs361072 and association with IR was also examined in 5895 non
      obese non-diabetic adults (NDNO). rs361072 was associated with HOMA-IR (p=4.10(
      4)) in NDO, so that C/C patients had a 17% decrease of this index (p=0.002). A
      statistical trend (p=1.1.10(-2)) for the same genotypic differences was also
      observed in NDNO adults, but of insignificant magnitude (4.2%). The distribution
      of rs361072 genotype was comparable in NDO, DO, DNO and NDNO individuals. Allele
      C of rs361072 is associated with a protection from IR in obese and non-obese
      adults, but has no significant effect, however, on diabetes risk in obese or non
      obese Europeans.

PMID- 19097922
TI  - A haplotype of the CYP4F2 gene associated with myocardial infarction in Japanese
      men.
AB  - This study assessed associations between the CYP4F2 gene and myocardial
      infarction (MI), using a haplotype-based case-control study of 234 MI patients
      and 248 controls genotyped for 5 single-nucleotide polymorphisms (rs3093105,
      rs3093135, rs1558139, rs2108622, rs3093200). For men, G allele frequency of
      rs2108622 and frequency of the T-C-G haplotype were significantly higher, and
      frequency of the T-C-A haplotype was significantly lower for MI patients than for
      controls (P=0.006, P=0.001 and P=0.002, respectively).

PMID- 19097923
TI  - Surgical management of vertebral malformation in a Manx cat.
AB  - A 15-week-old Manx kitten was presented for evaluation of progressive hind limb
      paresis and ataxia. Spinal radiographs and computed tomography revealed a
      malformation of T3 causing thoracic spinal cord compression. Decompressive
      surgery consisting of dorsal laminectomy, without vertebral stabilisation,
      resulted in improvement of clinical signs.

PMID- 19097924
TI  - Evaluation of endosonography as a new diagnostic tool for feline pancreatitis.
AB  - The purpose of this study was to evaluate endosonography (EUS) as a potential
      diagnostic tool for feline pancreatitis. Eleven healthy cats and six cats
      diagnosed with pancreatitis based on an increased serum feline pancreatic lipase
      immunoreactivity (fPLI) concentration were included. Transabdominal ultrasound
      (AUS) and EUS were performed in all cats. The widths of both pancreatic limbs and
      echogenicity and homogenicity were assessed by AUS and EUS. Finally, findings
      from both modalities were subjectively compared. In the healthy cats, the right
      pancreatic limb was significantly smaller on EUS compared to AUS. Also,
      subjectively, general visualization of the normal pancreas was superior with EUS
      and, the pancreatic margins and parenchyma could be resolved better with EUS in
      all sick patients. In this study, EUS findings did not alter the diagnosis in six
      cats with pancreatitis when compared to AUS. However, EUS may be useful in cases
      where AUS fails due to obesity, hyperechoic mesentery, or excessive intestinal
      gas.

PMID- 19097925
TI  - Personal digital assistants to collect tuberculosis bacteriology data in Peru
      reduce delays, errors, and workload, and are acceptable to users: cluster
      randomized controlled trial.
AB  - OBJECTIVES: To evaluate the effectiveness of a personal digital assistant (PDA)
      based system for collecting tuberculosis test results and to compare this new
      system to the previous paper-based system. The PDA- and paper-based systems were
      evaluated based on processing times, frequency of errors, and number of work
      hours expended by data collectors. METHODS: We conducted a cluster randomized
      controlled trial in 93 health establishments in Peru. Baseline data were
      collected for 19 months. Districts (n=4) were then randomly assigned to
      intervention (PDA) or control (paper) groups, and further data were collected for
      6 months. Comparisons were made between intervention and control districts and
      within-districts before and after the introduction of the intervention. RESULTS:
      The PDA-based system had a significant effect on processing times (p<0.001) and
      errors (p=0.005). In the between-districts comparison, the median processing time
      for cultures was reduced from 23 to 8 days and for smears was reduced from 25 to
      12 days. In that comparison, the proportion of cultures with delays >90 days was
      reduced from 9.2% to 0.1% and the number of errors was decreased by 57.1%. The
      intervention reduced the work-hours necessary to process results by 70% and was
      preferred by all users. CONCLUSIONS: A well-designed PDA-based system to collect
      data from institutions over a large, resource-poor area can significantly reduce
      delays, errors, and person-hours spent processing data.

PMID- 19097926
TI  - [Primary adenoid cystic carcinoma in breast].
AB  - Adenoid cystic carcinoma (ACC) of the breast is a rare neoplasm. We report two
      observations occurring in female patients, 54 and 65 years old, who consulted for
      a mastodynia. Clinical examination showed limited painful breast nodules. On
      ultrasound and mammography they are well-limited bulky mass without
      microcalcifications. Diagnosis was based on final histopathological exam
      completed by immunohistochemistry or after slides review. The two patients were
      treated by mammectomy plus adjuvant radiotherapy and remain alive in remission
      with a follow-up of 29 and 36 months.

PMID- 19097927
TI  - [Congenital pseudarthrosis of the forearm. Report of two cases and review of the
      literature].
AB  - Congenital pseudarthrosis of the forearm represents a rare entity which is often
      associated with neurofibromatosis type I. Isolated pseudarthrosis of the ulna is
      the most frequent deformity, followed by pseudarthrosis of the radius and both
      forearm bones. The treatment of these deformities remains difficult: conventional
      bone grafts rarely lead to complete fusion. The reconstruction by a vascularized
      fibular graft represents the treatment of choice if the radial head is not
      dislocated. This procedure allows restoration of a balance between radius and
      ulna during growth. The presence of a vascularized graft enhances the potential
      for bony fusion in a fibrous environment. In cases of isolated ulna
      pseudarthrosis, a luxation of the proximal radial epiphysis may occur when the
      ulnar deformity increases with time. The single-bone forearm represents a salvage
      procedure that creates a stable upper limb with a satisfactory wrist and elbow
      function. The two clinical cases of a pseudarthrosis of both forearm bones and of
      an ulna pseudarthrosis are presented.

PMID- 19097928
TI  - [Role of para-aortic lymphadenectomy in cervical carcinoma].

PMID- 19097929
TI  - The role of KLF6 and its splice variants in cancer therapy.
AB  - The Kruppel-like zinc finger transcription factor (KLF6) gene encodes a family of
      proteins generated through alternative splicing involved in the regulation of
      cancer development and progression. Alternative splicing of the KLF6 gene results
      in the production of at least four alternatively spliced isoforms, two of which
      are extensively discussed in this review. The full length form of the KLF6 gene
      is a tumor suppressor gene that is frequently inactivated by loss of
      heterozygozity (LOH), somatic mutation, and/or decreased expression in human
      cancer. While the exact mechanisms underlying KLF6's tumor suppressor roles are
      not completely known, a number of highly relevant, overlapping pathways have been
      described: transactivation of p21 in a p53-independent manner, reduction of
      cyclin D1/cdk4 complexes via interaction with cyclin D1, inhibition of c-Jun
      proto-oncoprotein activities, decreased VEGF expression, and induction of
      apoptosis. Kruppel-like factor 6 splice variant 1 (KLF6-SV1) is an oncogenic
      splice variant of the KLF6 tumor suppressor gene that is specifically
      overexpressed in a number of human cancers. Increased KLF6-SV1 expression is
      associated with poor prognosis in prostate, lung, and ovarian cancer.
      Furthermore, KLF6-SV1 has been shown to be biologically active, antagonizing the
      tumor suppressor function of KLF6 and promoting tumor growth and dissemination in
      both ovarian and prostate cancer models. In addition, a common germline
      polymorphism in the KLF6 gene associated with increased prostate cancer risk in a
      large multi-institutional study of 3411 men results in increased expression of
      KLF6-SV1. Furthermore, recent studies have demonstrated that targeted reduction
      of KLF6-SV1 results in the induction of spontaneous apoptosis in cell culture,
      synergizes with chemotherapeutic agents like cisplatin, and results in
      significant tumor regression in vivo. Combined, these data make the KLF6 gene
      family a compelling therapeutic target for both the treatment of localized as
      well as metastatic cancer.

PMID- 19097931
TI  - Structure and spectroscopic properties of phthalocyaninato zinc(II) complexes
      fused with different number of 15-crown-5 moieties.
AB  - A series of structurally closely related phthalocyaninato zinc(II) complexes
      fused with different number and/or disposition of 15-crown-5 groups at the
      peripheral positions Zn(Pc') (1-6) [Pc'=Pc, Pc(15C5), Pc(opp-15C5)(2), Pc(adj
      15C5)(2), Pc(15C5)(3), Pc(15C5)(4); Pc=unsubstituted phthalocyaninate;
      Pc(15C5)=2,3-(15-crown-5)phthalocyaninate; Pc(opp-15C5)(2)=2,3,16,17-bis(15-crown
      5)phthalocyaninate; Pc(adj-15C5)(2)=2,3,9,10-bis(15-crown-5)phthalocyaninate;
      Pc(15C5)(3)=2,3,9,10,16,17-tris(15-crown-5)phthalocyaninate;
      Pc(15C5)(4)=2,3,9,10,16,17,24,25-tetrakis(15-crown-5)phthalocyaninate] have been
      designed, prepared, and spectroscopically characterized. The effect of number and
      dispositions of 15-crown-5 moieties on their electronic and vibrational
      spectroscopic properties was understood by systematic investigation over the
      electronic absorption, infra-red (IR), and Raman spectra of this series of
      phthalocyaninato zinc complexes. In addition, density functional theory (DFT) and
      time-dependent density functional theory (TD-DFT) calculations were carried out
      to comparatively describe the molecular structures, atomic charges, electronic
      absorption spectra, infrared (IR), and Raman spectra of 1-6, revealing the nature
      of the main transitions in electronic absorption spectra and identifying the
      vibration modes in the IR and Raman spectra of the series of six complexes with
      the assistance of animated pictures produced on the basis of the normal
      coordinates.

PMID- 19097930
TI  - Overexpression of human beta-defensin-3 in oral dysplasia: potential role in
      macrophage trafficking.
AB  - Human beta-defensins (hBDs) are small, cationic antimicrobial peptides produced
      by oral and other mucosal epithelia. More recently, hBDs have been shown to
      regulate adaptive immunity. In this study, we provide new information about the
      potential role of hBD-3 in the progression of oral cancer. In normal human oral
      epithelia, hBD-3 is produced by mitotically active cells in the basal layers of
      oral epithelium, whereas hBD-1 and -2 are coexpressed in the differentiated
      spinosum and granulosum layers. Interestingly, premalignant cells in carcinoma in
      situ lesions overexpress hBD-3, but not hBD-1 and hBD-2, correlating with
      specific recruitment and infiltration of macrophages. Our in vitro studies
      demonstrate that hBD-3 chemoattracts THP-1 monocytic cells and that epidermal
      growth factor (EGF) significantly induces hBD-3 expression in oral epithelial
      cells via mitogen-activated protein kinase (MAPK) kinase MEK1/2, p38 MAPK,
      protein kinase C (PKC), and phosphoinositide 3 kinase (PI3K), but not via Janus
      kinase (JAK) and signal transducer and activator of transcription (STATs). These
      results suggest that hBD-3 serves as a mitogen responsive gene in the initiation
      of oral cancer and may act as a motility signal to recruit tumor-associated
      macrophages.

PMID- 19097932
TI  - On the vibrational spectra of HSO and SOH.
AB  - The harmonic and fundamental vibrational frequencies, rotational constants,
      vibration-rotation corrections and Zero point energies of HSO and SOH and their
      deuterated isomers (DSO and SOD) have been determined employing the CCSD(T)
      methodology in conjunction with the aug-cc-pV(X+d)Z and cc-pwCVQZ basis sets. The
      calculated fundamental frequencies of SOH are 830, 1150 and 3577cm(-1), for the
      upsilon(SO), upsilon(bend) and upsilon(OH), respectively. In the case of HSO the
      computed fundamentals are 1002, 1077 and 2335cm(-1), for the upsilon(SO),
      upsilon(bend) and upsilon(SH), respectively. The values are discussed in terms of
      the experimental determinations available. The rotational constants reported for
      HSO are in reasonable agreement with experiment; the computed values are 301,271,
      20,557 and 19,192MHz. In the case of SOH, for the first time, we report the
      rotational constants including vibration-rotation corrections, they are: 654,236,
      16,621, 16,178MHz. The force fields calculated allowed as to estimate accurate
      ZPEs, the suggested values are 6.48 and 8.19kcal/mol for HSO and SOH,
      respectively. Finally, we recommend the following structural parameters for HSO
      r(SO)=1.4924A, r(SH)=1.3649A and angleHSO=104.76 degrees ; whereas for SOH we
      recommend r(SO)=1.6302A, r(OH)=0.9629A and angleSOH=107.97 degrees .

PMID- 19097933
TI  - Distribution of human papillomavirus types in anogenital warts of men.
AB  - BACKGROUND: A wide spectrum of human papillomavirus (HPV) types can infect the
      male genitalia. An HPV vaccine covering HPV6 and 11 is now available. Detailed
      data on the distribution of these two types in anogenital warts is needed to
      assess the potential benefits of the vaccine. STUDY DESIGN: Anogenital wart
      specimens collected from 130 Chinese men were examined for HPV-type distribution
      by a method that covers a broad spectrum of high- and low-risk HPVs, and able to
      reveal multiple types from a single specimen. RESULTS: Forty-four (33.8%) of the
      130 specimens had a coinfection with multiple HPV types. In 63.1% of cases, only
      HPV6 and/or HPV11 were/was found. In 26.2% of cases, HPV6 and/or HPV11 were/was
      found together with one or more other HPV types. In 10.8% of specimens, only non
      6/11 HPV types were found. HPV16 and/or 18 were/was found in 12 (9.2%) specimens,
      with majority (8/12, 66.7%) of which existed as coinfections with HPV6/11. Other
      HPV types found included HPV39, 51, 52, 55, 59, 61, 62, 68, 58, 72, 81, 83, 84
      and CP6108. CONCLUSIONS: A substantial proportion of HPV6/11-positive male
      anogenital warts are coinfected with other HPV types. The efficacy of HPV6/11
      vaccine for preventing these lesions needs to be defined before the benefits of
      vaccinating men can be precisely assessed.

PMID- 19097935
TI  - Musings on the real problems.

PMID- 19097934
TI  - Ocular vestibular-evoked myogenic potentials elicited from monaural versus
      binaural acoustic stimulations.
AB  - OBJECTIVE: This study compared the ocular vestibular-evoked myogenic potentials
      (oVEMPs) that are elicited (recorded) in response to monaural and separately,
      simultaneous binaural acoustic stimulations. The optimal stimulation mode for
      oVEMPs was also determined. METHODS: Twenty healthy volunteers (14 men and 6
      women, aged from 22 to 33 years, mean 28 years) without any previous ear
      disorders were enrolled in this study. Each subject underwent oVEMP testing using
      monaural acoustic stimulation (Mon-oVEMP) with different stimulus intensities,
      and with bilateral recording. On another day, the same volunteers underwent oVEMP
      testing using simultaneous binaural acoustic stimulation and bilateral recording
      (Bin-oVEMP). RESULTS: With 95 dB nHL tone burst stimulation, the biphasic nI-pI
      waveforms were recorded with maximal amplitudes from the electrodes located below
      the eyes contralateral to the side of acoustic stimulation while the subject was
      gazing upward. Significant correlations were identified between Mon-oVEMPs and
      Bin-oVEMPs with respect to threshold, latencies and amplitude. However, no
      significant difference existed between Mon-oVEMPs and Bin-oVEMPs in terms of the
      response rate, threshold, latency or amplitude. CONCLUSIONS: The Bin-oVEMP test
      yields the same information as the Mon-oVEMP test, but the duration of recording
      in the former is shorter than the latter. SIGNIFICANCE: The Bin-oVEMP test may be
      a more convenient screening tool for evaluating the crossed vestibulo-ocular
      reflex.

PMID- 19097936
TI  - Primary skeletal muscle cells trigger spontaneous Toxoplasma gondii tachyzoite-to
      bradyzoite conversion at higher rates than fibroblasts.
AB  - Toxoplasma gondii is one of the most common eukaryotic parasites and an important
      opportunistic pathogen of humans. The interconversion from proliferative
      tachyzoites into quiescent encysted bradyzoites plays pivotal roles in the
      lifelong persistence of T. gondii in its host and the pathogenesis of
      toxoplasmosis. Stage conversion and persistence in skeletal muscle tissue may be
      particularly important for the food-borne transmission of T. gondii to humans via
      raw or undercooked meat products. Here, we have followed the transition of
      tachyzoites to bradyzoites after infection of skeletal muscle cells (SkMC).
      Primary murine myoblasts were differentiated to multinucleated syncytial myotubes
      that displayed regular contractions in vitro and expressed myogenic markers Myf5
      and MyoD. Tachyzoites of T. gondii invaded SkMC within 4h of infection and
      started to replicate within 24h of infection. Remarkably, intracellular
      tachyzoites readily differentiated to bradyzoites in SkMC without the need of
      exogenous stress factors. Double immunofluorescence labelling revealed
      significantly higher percentages of bradyzoite-containing vacuoles in SkMC than
      in murine fibroblasts at 24h until 6 days after infection. Furthermore,
      transcript levels of bradyzoite-specific ENO1 but not tachyzoite-specific ENO2
      strongly increased in T. gondii-infected SkMC until 6 days of infection. These
      findings indicate that the commitment of T. gondii to differentiate to
      bradyzoites in SkMC does not require exogenous stress factors but could be rather
      regulated by cell-type specific factors.

PMID- 19097937
TI  - Targeting proteasomes for cardioprotection.
AB  - The ubiquitin-proteasome system (UPS) plays a central role in intracellular
      protein degradation and regulates many cellular processes, including cell
      proliferation, inflammation, adaptation to stress, cell death, and the removal of
      damaged or misfolded proteins. Numerous studies have demonstrated that altered
      UPS function is involved in the pathogenesis of a wide range of cardiac diseases
      including hypertrophy and failure, myocardial ischemia, atherosclerosis, and
      diabetic cardiovascular disease. Impairment of proteasome function is a common
      feature of cardiac disease; however several studies have also demonstrated
      increased proteasome activity in models similar but not identical with those
      having decreased function. Recent studies have shown that use of proteasome
      inhibitors before or following production of the model of cardiac disease may
      confer cardioprotection under certain conditions.

PMID- 19097938
TI  - TRPV1 antagonists: the challenges for therapeutic targeting.
AB  - The capsaicin receptor TRPV1 (transient receptor potential cation channel,
      subfamily V, member 1) is a polymodal nociceptor whose expression is upregulated
      in several painful disorders. At present, potent small molecule TRPV1 antagonists
      are undergoing clinical trials in patients with chronic pain. Clinical
      development of TRPV1 antagonists is, however, facing new challenges. Many drug
      candidates evoke a febrile reaction that varies among patients. We speculate that
      TRPV1 gene polymorphism might be an underlying cause of the inter-subject
      variability in pain sensation and response to TRPV1 antagonists. This newly
      understood and yet to be fully validated aspect of pain suggests that pain
      management based on regulating the TRPV1 receptor might require a personalized
      approach for effective clinical outcome. Here, we provide our perspectives on
      current progress in targeting TRPV1.

PMID- 19097939
TI  - When mutant p53 plays hide and seek: a new challenge for diagnosis and therapy?
AB  - p53 missense mutations observed in human cancers are often associated with an
      increased level of p53 protein in the tumour. Using mouse models, Terzian et al.
      recently showed that this accumulation of mutant p53 protein is not associated
      with specific properties of the protein itself but instead depends on the
      endogenous genetic background of the tumours and on two important genes, mouse
      double minute 2 (Mdm2) and the cyclin kinase inhibitor p16INK4a. Mice expressing
      mutant p53 in the absence of Mdm2 display more aggressive metastatic tumours. In
      light of these observations, targeting the MDM2-p53 interaction for therapy of
      human cancer could be more complicated than previously anticipated.

PMID- 19097940
TI  - Ocular gene therapy: current progress and future prospects.
AB  - As gene therapy begins to produce its first clinical successes, interest in
      ocular gene transfer has grown owing to the favorable safety and efficacy
      characteristics of the eye as a target organ for drug delivery. Important
      advances also include the availability of viral and non-viral vectors that are
      able to efficiently transduce various ocular cell types, the use of intraocular
      delivery routes and the development of transcriptional regulatory elements that
      allow sustained levels of gene transfer in small and large animal models after a
      single administration. Here, we review recent progress in the field of ocular
      gene therapy. The first experiments in humans with severe inherited forms of
      blindness seem to confirm the good safety and efficacy profiles observed in
      animal models and suggest that gene transfer has the potential to become a
      valuable therapeutic strategy for otherwise untreatable blinding diseases.

PMID- 19097941
TI  - Desmoteplase and imaging science.

PMID- 19097942
TI  - Intravenous desmoteplase in patients with acute ischaemic stroke selected by MRI
      perfusion-diffusion weighted imaging or perfusion CT (DIAS-2): a prospective,
      randomised, double-blind, placebo-controlled study.
AB  - BACKGROUND: Previous studies have suggested that desmoteplase, a novel
      plasminogen activator, has clinical benefit when given 3-9 h after the onset of
      the symptoms of stroke in patients with presumptive tissue at risk that is
      identified by magnetic resonance perfusion imaging (PI) and diffusion-weighted
      imaging (DWI). METHODS: In this randomised, placebo-controlled, double-blind,
      dose-ranging study, patients with acute ischaemic stroke and tissue at risk seen
      on either MRI or CT imaging were randomly assigned (1:1:1) to 90 microg/kg
      desmoteplase, 125 microg/kg desmoteplase, or placebo within 3-9 h after the onset
      of symptoms of stroke. The primary endpoint was clinical response rates at day
      90, defined as a composite of improvement in National Institutes of Health stroke
      scale (NIHSS) score of 8 points or more or an NIHSS score of 1 point or less, a
      modified Rankin scale score of 0-2 points, and a Barthel index of 75-100.
      Secondary endpoints included change in lesion volume between baseline and day 30,
      rates of symptomatic intracranial haemorrhage, and mortality rates. Analysis was
      by intention to treat. This study is registered with ClinicalTrials.gov,
      NCT00111852. FINDINGS: Between June, 2005, and March, 2007, 193 patients were
      randomised, and 186 patients received treatment: 57 received 90 microg/kg
      desmoteplase; 66 received 125 microg/kg desmoteplase; and 63 received placebo.
      158 patients completed the study. The median baseline NIHSS score was 9 (IQR 6
      14) points, and 30% (53 of 179) of the patients had a visible occlusion of a
      vessel at presentation. The core lesion and the mismatch volumes were small
      (median volumes were 10.6 cm(3) and 52.5 cm(3), respectively). The clinical
      response rates at day 90 were 47% (27 of 57) for 90 microg/kg desmoteplase, 36%
      (24 of 66) for 125 microg/kg desmoteplase, and 46% (29 of 63) for placebo. The
      median changes in lesion volume were: 90 microg/kg desmoteplase 14.0% (0.5
      cm(3)); 125 microg/kg desmoteplase 10.8% (0.3 cm(3)); placebo -10.0% (-0.9
      cm(3)). The rates of symptomatic intracranial haemorrhage were 3.5% (2 of 57) for
      90 microg/kg desmoteplase, 4.5% (3 of 66) for 125 microg/kg desmoteplase, and 0%
      for placebo. The overall mortality rate was 11% (5% [3 of 57] for 90 microg/kg
      desmoteplase; 21% [14 of 66] for 125 microg/kg desmoteplase; and 6% [4 of 63] for
      placebo). INTERPRETATION: The DIAS-2 study did not show a benefit of desmoteplase
      given 3-9 h after the onset of stroke. The high response rate in the placebo
      group could be explained by the mild strokes recorded (low baseline NIHSS scores,
      small core lesions, and small mismatch volumes that were associated with no
      vessel occlusions), which possibly reduced the potential to detect any effect of
      desmoteplase. FUNDING: PAION Deutschland GmbH; Forest Laboratories.

PMID- 19097943
TI  - Profile of adults with congenital heart disease having a good, moderate, or poor
      quality of life: a cluster analytic study.
AB  - AIMS: The purpose of the study was to assess the profile of adult patients with
      congenital heart disease who reported a good, moderate, or poor quality of life.
      METHODS: We conducted a secondary analysis of data from a large-scale quality-of
      life study that included 627 patients. Demographic and clinical variables were
      retrieved from the medical records and functional status from patient interviews.
      Overall quality of life was measured using a Linear Analogue Scale. Using K-means
      cluster analysis, we categorized subjects into a 3-cluster solution: good,
      moderate, or poor quality of life. RESULTS: Four hundred ninety patients (78.1%)
      clustered into the good quality-of-life category; 126 patients (20.1%) clustered
      into the moderate quality-of-life category; and 11 patients (1.8%) clustered into
      the poor quality-of-life category. Poorer quality of life was associated with
      lower educational level, unemployment or disability, associated syndromes,
      instability of the heart disease, and a poorer functional status. CONCLUSION:
      Over three-quarters of the patients had a good quality of life, whereas only a
      small proportion had a poor quality of life. Specific demographic and clinical
      characteristics associated with a poor quality of life could assists in
      identifying patients at risk for developing a poor quality of life.

PMID- 19097944
TI  - A rebuttal to the comments on the genome order index.
AB  - Recently, Elhaik et al. [Elhaik, E., Graur, D., Josic, K., 2008. 'Genome order
      index' should not be used for defining compositional constraints in nucleotide
      sequences. Comp. Biol. Chem. 32, 147] commented on the genome order index, which
      is defined as S=a(2)+c(2)+g(2)+t(2) where a, c, g and t denote corresponding base
      frequencies. They claimed that (1) "S<1/3 is in fact a mathematical property that
      is always true", and (2) "S is strictly equivalent to and derivable from the
      Shannon H function". The first claim is apparently wrong: for instance, when
      a=c=0.5, g=t=0, S=0.5>1/3. The second claim is also incorrect because S and H are
      different special cases of the alpha-order entropy, having different functional
      forms that are neither strictly derivable from nor equivalent to each other.
      Therefore, the conclusions made in their comments are wrong.

PMID- 19097945
TI  - Autoimmune pathology accounts for common manifestations in a wide range of neuro
      psychiatric disorders: the olfactory and immune system interrelationship.
AB  - Smell has traditionally been considered a less important sense when compared to
      sight or hearing, but recent research has unraveled important features inherent
      to the sense of smell. Once considered just a chemical sensor for sampling the
      environment, data from animal models and human studies currently imply numerous
      and complex effects of smell on behavior, mood, and on the immune response. In
      this review we discuss a possible inter-relationship between olfactory
      impairment, autoimmunity and neurological/psychiatric symptoms in several
      diseases affecting the central nervous system (CNS) such as Parkinson,
      Alzheimer's disease, autism, schizophrenia, multiple sclerosis and
      neuropsychiatric lupus erythematosus. We suggest that common manifestations are
      not mere coincidences. Current data from animal models show that neuropsychiatric
      manifestations are intimately associated with smell impairment, and autoimmune
      dysregulation, via autoantibodies (anti-NMDAR, anti-ribosomal P) or other
      mechanisms. From clues of pathological manifestations, we propose a novel
      approach to the understanding of the interactions between the CNS, the smell and
      the immune system.

PMID- 19097946
TI  - Chromosomal dynamics at the Shh locus: limb bud-specific differential regulation
      of competence and active transcription.
AB  - The expression of Sonic hedgehog (Shh) in mouse limb buds is regulated by a long
      range enhancer 1 Mb upstream of the Shh promoter. We used 3D-FISH and chromosome
      conformation capture assays to track changes at the Shh locus and found that long
      range promoter-enhancer interactions are specific to limb bud tissues competent
      to express Shh. However, the Shh locus loops out from its chromosome territory
      only in the posterior limb bud (zone of polarizing activity or ZPA), where Shh
      expression is active. Notably, while Shh mRNA is detected throughout the ZPA,
      enhancer-promoter interactions and looping out were only observed in small
      fractions of ZPA cells. In situ detection of nascent Shh transcripts and unstable
      EGFP reporters revealed that active Shh transcription is likewise only seen in a
      small fraction of ZPA cells. These results suggest that chromosome conformation
      dynamics at the Shh locus allow transient pulses of Shh transcription.

PMID- 19097947
TI  - Electrocatalytic activity of [Ru(bpy)3]2+ for hypoxanthine oxidation studied by
      rotating electrode methods.
AB  - A rotating ring-disk electrode method for studying the electrochemical oxidation
      of hypoxanthine (Hx) catalyzed by [Ru(bpy)(3)](3+/2+) reaction has been
      developed. A limiting current plateau for [Ru(bpy)(3)](3+/2+) reaction is
      exhibited on the rotating disk or ring electrode. It is found that
      [Ru(bpy)(3)](2+) has excellent electrocatalytic activities for Hx oxidation. The
      electrocatalytic currents increase linearly with the rise of Hx concentrations in
      the range from 0.2 to 1.2 mmol/L on the immobile Pt electrode. Whereas, high
      rotation rate or Hx concentration makes the voltammetric curves on the rotating
      disk electrode display the sharp peaks instead of the limiting current plateaus.
      The oxidized mechanisms of Hx catalyzed by Ru(bpy)(3)(3+/2+) reaction are
      discussed in detail.

PMID- 19097948
TI  - Investigating the in vitro metabolism of veratridine: characterization of
      metabolites and involved cytochrome P450 isoforms.
AB  - Veratridine is a lipid-soluble alkaloid extracted from Veratrum officinale and
      other species of the family Liliaceae. Veratridine prevents inactivation of Na(+)
      channel via binding the receptor site 2, causes influx of sodium ion and
      depolarization and induces apoptosis of neuronal cells. In the present study, we
      investigated the metabolism of veratridine and the effects of selective
      cytochrome P450 (CYP) inhibitors on the metabolism of veratridine in rat liver
      microsomes. The metabolites were separated and assayed by liquid-chromatography
      electrospray ionization-ion trap tandem mass spectrometry (LC-ESI-QIT-MSn), and
      further identified by their mass spectra and chromatographic behaviors. Result
      showed that four CYP isoforms (CYP1A, CYP2B, CYP2E1, CYP3A) were involved in the
      metabolism of veratridine in vitro and seven metabolites of veratridine were
      detected incubating with rat liver microsomes. Some of the metabolites were
      presumed to be potential mediates of neurotoxicity via protein binging. Further
      research in vivo needs to link the metabolism of veratridine to its toxicity.

PMID- 19097949
TI  - HPLC methods for determination of two novel thiosemicarbazone anti-cancer drugs
      (N4mT and Dp44mT) in plasma and their application to in vitro plasma stability of
      these agents.
AB  - The aim of this study was to develop and validate HPLC methods for the
      determination in plasma of two novel thiosemicarbazone anti-tumour drugs
      developed in our laboratories (Dp44mT and N4mT). The appropriate separations were
      achieved using a HS F5 HPLC column with the mobile phase composed of a mixture of
      either acetate buffer/EDTA or EDTA and acetonitrile (62:38 and 50:50, v/v,
      respectively). The plasma samples were pretreated with SPE (phenyl and C18,
      respectively). Furthermore, these methods were successfully applied to in vitro
      plasma stability experiments. The investigation has clearly shown that both
      thiosemicarbazones are markedly more stable in plasma than their aroylhydrazone
      forerunners.

PMID- 19097950
TI  - Determination of norelgestromin in rabbit plasma by LC-MS/MS and its application
      to the pharmacokinetic study of ORTHO EVRA.
AB  - A simple, sensitive and rapid method is presented for the determination of
      norelgestromin using LC-MS/MS, interfaced via an electrospray ionization (ESI)
      probe, operating in the positive ion mode with multiple reaction monitoring
      (MRM). The method was developed and validated over the concentration range of
      0.05-20 ng/ml, and showed excellent linearity. The intra- and inter-assay
      accuracy error and precision were ranging from -2.3% to 6.0% of nominal values
      and 2.2% to 7.8% over the three concentration levels evaluated. The concentration
      of formic acid in mobile phase was optimized to achieve satisfactory injection
      reproducibility and sensitivity, and sample preparation was optimized, with only
      1.6 ml organic solvents used in performing the liquid-liquid extraction. The
      method has been successfully applied to a pharmacokinetic study of the ORTHO EVRA
      patch in rabbits.

PMID- 19097951
TI  - Liquid chromatography-mass spectrometry analysis of macranthoidin B,
      macranthoidin A, dipsacoside B, and macranthoside B in rat plasma for the
      pharmacokinetic investigation.
AB  - A liquid chromatography-electrospray ionization-mass spectrometry method has been
      developed and validated for identification and quantification of four major
      bioactive saponins in rat plasma after oral administration of extraction of
      saponins from Flos Lonicerae, i.e., macranthoidin B, macranthoidin A, dipsacoside
      B, and macranthoside B. Plasma samples were extracted with solid-phase
      extraction, separated on a Shim-pack CLC-ODS column and detected by MS in
      negative selective ion monitoring mode. Calibration curves offered linear ranges
      of two orders of magnitude with r(2)>0.999. The method showed the low limit
      quantification of 7.72, 6.06, 7.16, and 1.43 ng/mL for macranthoidin B,
      macranthoidin A, dipsacoside B, and macranthoside B, respectively. The inter- and
      intra-CV precision (R.S.D.) were all within 10% and accuracy (% bias) ranged from
      -10 to 10%. The overall recovery was more than 70%. This developed method was
      subsequently successfully applied to pharmacokinetic profiles of the four
      saponins in rats. After oral administration of extraction of saponins in rats,
      the concentration-time course was found to be the double peaks of curve.

PMID- 19097952
TI  - Bioactivity of electro-thermally poled bioactive silicate glass.
AB  - A 45S5 bioactive glass (nominal composition: 46.1 mol.% SiO2, 2.6 mol.% P2O5,
      26.9 mol.% CaO, 24.4 mol.% Na2O) was electrothermally poled by applying voltages
      up to 750 V for 45 min at 200 degrees C, and the thermally stimulated
      depolarization currents (TSDCs) were recorded. Changes in chemical composition
      and electrical properties after poling were investigated by TSDC measurements,
      impedance spectroscopy and scanning electron microscopy with energy dispersive X
      ray spectroscopy (SEM/EDX). The poling led to the formation of interfacial layers
      underneath the surface in contact with the electrodes. Under the positive
      electrode, the layer was characterized by Na+ ion depletion and by a negative
      charge density, and the layer was more resistive than the bulk. The influence of
      poling on the bioactivity was studied by immersion of samples in simulated body
      fluid (SBF) with subsequent cross-sectional SEM/EDX and X-ray diffraction
      analysis. It was found that poling leads to morphological changes in the silica
      rich layer and to changes in the growth rate of amorphous calcium phosphate and
      bone-like apatite on the glass surface. The bone-like apatite layer under the
      positive electrode was slightly thicker than that under the negative electrode.

PMID- 19097953
TI  - New modalities in the treatment of pregnancies complicated by diabetes: drugs and
      devices.
AB  - The development of drugs and devices in the treatment of pregnancies complicated
      by diabetes is in constant forward progression to compensate for pancreatic beta
      cell insufficiency. Maternal hyperglycemia during pregnancy is of particular
      interest due to the severe consequences that surface when a fetus is in
      development. The drugs that are currently recommended for use during pregnancy
      include rapid-acting insulin analogs lispro and aspart for meal-related bolus
      insulin and intermediate-acting NPH for basal insulin. Oral anti-diabetic agents
      are not recommended for use during pregnancy. Better control may be achieved with
      the incorporation of real-time glucose sensors and new insulin pumps with hopes
      of improving pregnancy outcome.

PMID- 19097954
TI  - Varicella in the fetus and newborn.
AB  - Varicella (chickenpox) in pregnancy is unusual because most women of childbearing
      age are immune. It can, however, cause significant morbidity for the pregnant
      woman and in rare cases cause congenital varicella syndrome. The incidence of
      congenital varicella syndrome after maternal varicella during the first two
      trimesters is <1% across multiple cohort studies. Maternal infection in the third
      trimester is not associated with congenital varicella syndrome, but the infant
      may develop herpes zoster during the first one or two years. Maternal infection
      just before or after delivery presents a high risk for disseminated varicella in
      the infant. Serious infection can be prevented with passive antibody prophylaxis
      and antiviral therapy. Maternal herpes zoster does not result in adverse fetal or
      neonatal outcomes.

PMID- 19097955
TI  - A technique for applying Biobrane to the face as a single sheet.

PMID- 19097956
TI  - Quantitative analysis of normal smile with 3D stereophotogrammetry--an aid to
      facial reanimation.
AB  - INTRODUCTION: Rubin observed that there was a great deal of variation in smiles.
      [Rubin LR. The anatomy of a smile: its importance in the treatment of facial
      paralysis. Plast Reconstr Surg 1974;53:384-7] Smile reconstruction requires an
      understanding of the facial movements that occur during a normal smile. Facial
      reanimation should be tailored for each individual patient so that the movements
      on the reconstructed side are similar to that on the normal side. AIM: The aim of
      this study is to produce a quantitative analysis of smiles, as a basis for smile
      reconstruction and to compare our subject's smiles to the classification
      suggested by Rubin. METHOD: The smiles of 71 volunteers were analysed using three
      dimensional (3D) stereophotogrammetry in x, y and z vectors. Each subject had the
      distances and angles of 10 surface landmarks (cheilion left and right (L&R),
      labiale superius/inferius, mid-lateral upper/lower lip (L&R), nasolabial fold
      (L&R)) moved from the relaxed position to that in a maximum smile. All subjects'
      smiles were classified into the Rubin subtypes of corner of the mouth, canine and
      full-denture smile. RESULTS: The average distances and angles moved by oral
      landmarks during a smile in a 3D plane were--cheilion: 16.6mm at 31 degrees ;
      labiale superius: 8.2mm at 31 degrees; upper mid-lateral lip: 10.5mm at 25
      degrees; labiale inferius: 5.3mm at -56 degrees; lower mid-lateral lip: 7.8mm at
      41 degrees and nasolabial fold: 12.6mm at 33 degrees . Our population results for
      the smile subtypes suggested by Rubin were--corner-of-the-mouth smile: 77%,
      canine smile: 15% and full-denture smile: 8%. CONCLUSION: Our study offers a
      simple quantitative method for measuring the smile to assess the outcome of
      reanimation surgery between different surgical procedures and units. Proportions
      of our study group with corner-of-the-mouth, canine and full-denture smiles were
      consistent with Rubin's study.

PMID- 19097957
TI  - Rats, cats, and elephants, but still no unicorn: induced pluripotent stem cells
      from new species.
AB  - Two independent studies in this issue of Cell Stem Cell (Liao et al., 2009; Li et
      al., 2009) derive rat induced pluripotent stem cells (iPSCs). In one report, the
      method used results in rat and human iPSCs that exhibit phenotypic traits similar
      to mouse embryonic stem cells.

PMID- 19097958
TI  - Generation of rat and human induced pluripotent stem cells by combining genetic
      reprogramming and chemical inhibitors.

PMID- 19097959
TI  - Generation of induced pluripotent stem cell lines from adult rat cells.

PMID- 19097960
TI  - Dexmedetomidine: more than a sedative and analgesic.

PMID- 19097962
TI  - Propofol infusion shortens and attenuates oxidative stress during one lung
      ventilation.
AB  - BACKGROUND: Resuming two lung ventilation (2LV) from one lung ventilation (OLV)
      has been proven to induce significant oxidative stress, mainly by superoxide
      release. Although total intravenous anesthesia and inhalational anesthesia are
      both used in thoracic surgery, different anesthetics may alter the
      oxidant/antioxidant balance. METHODS: Thirty patients undergoing thoracic surgery
      were randomly allocated to the propofol infusion (intravenous) group or
      isoflurane (inhalational) group after induction and placement of a double lumen
      endobronchial tube. Reactive oxygen species (ROS) production and total
      antioxidant status (TAS) were measured during OLV and 2LV manipulations. Blood
      samples were taken in the lateral position before OLV (T1), immediately before
      resuming 2LV (T2), and 5 minutes (T3) and 20 minutes (T4) after resuming 2LV, for
      measurement of ROS. RESULTS: ROS production increased significantly at T3 and T4
      in both groups but to a lesser extent in the propofol infusion group. TAS levels
      increased with time in the propofol group but not in the isoflurane group.
      CONCLUSION: Propofol infusion, compared with isoflurane inhalation, attenuates
      ROS production and limits it for 20 minutes after resuming 2LV from OLV. Propofol
      infusion may be beneficial to patients with inadequate antioxidant capacity.

PMID- 19097961
TI  - Effects of dexmedetomidine on regulating pulmonary inflammation in a rat model of
      ventilator-induced lung injury.
AB  - BACKGROUND: We sought to elucidate the effects of dexmedetomidine, a selective
      alpha2-adrenergic receptor agonist, on the regulation of pulmonary inflammation
      in ventilator-induced lung injury (VILI) in a rat model. METHODS: A total of 64
      adult male Sprague-Dawley rats were assigned to receive either standard
      ventilation (tidal volume 10 mL/kg; respiratory rate 50 breaths/minute), high
      tidal volume ventilation (HVT: tidal volume 20 mL/kg; respiratory rate 50
      breaths/minute), HVT plus dexmedetomidine (0.5, 2.5 or 5.0 microg/kg per hour),
      or HVT plus dexmedetomidine (0.5, 2.5 or 5.0 microg/kg per hour) and yohimbine
      (the alpha2-adrenergic receptor antagonist) (n = 8 in each group). The doses of
      dexmedetomidine were chosen to correspond to 1, 5 and 10 times the clinical dose
      (0.5 microg/kg per hour). After maintaining ventilation for 4 hours, rats were
      sacrificed and pulmonary inflammatory changes as well as the upregulation of
      pulmonary inflammatory molecules were evaluated. RESULTS: Histological and
      arterial blood gas analyses confirmed that HVT induced significant lung injury.
      HVT also significantly increased the pulmonary concentrations of chemokines (e.g.
      macrophage inflammatory protein-2), cytokines (e.g. tumor necrosis factor-alpha,
      interleukin [IL]-1beta, and IL-6), inducible nitric oxide synthase/nitric oxide,
      cyclooxygenase-2/prostaglandin E2. Dexmedetomidine at the dose of 5.0 microg/kg
      per hour, but not at 0.5 and 2.5 microg/kg per hour, significantly attenuated the
      effects of HVT. Moreover, these effects of dexmedetomidine were significantly
      attenuated by yohimbine. CONCLUSION: Dexmedetomidine at clinically relevant doses
      had no significant effect in attenuating VILI. In contrast, dexmedetomidine at a
      dose approximately 10 times higher than the clinical dose significantly
      attenuated VILI. These effects of dexmedetomidine were mediated, at least in
      part, by the alpha2-adrenergic receptor.

PMID- 19097963
TI  - Efficacy of granisetron in preventing postanesthetic shivering.
AB  - BACKGROUND: Recently, 5-hydroxytryptamine 3 (5-HT3) receptor antagonists have
      been reported to prevent postanesthetic shivering. This placebo-controlled study
      was performed to evaluate the efficacy of granisetron, a 5-HT3 antagonist, in
      comparison with meperidine and tramadol in preventing postanesthetic shivering.
      METHODS: In this prospective, randomized, double-blind study, 132 ASA I and II
      patients undergoing elective orthopedic surgery under standardized general
      anesthesia were included. At the end of surgery, patients were randomly assigned
      to one of four groups (each group n = 33) using a double-blinded protocol. Group
      T received 1 mg/kg tramadol, group G received 40 microg/kg granisetron (an
      antiemetic dose), group M received 0.4 mg/kg meperidine, and group P received
      saline 0.9% as placebo. Shivering was graded according to the following: 0 = no
      shivering; 1 = piloerection, peripheral vasoconstriction or peripheral cyanosis
      without other cause; 2 = visible muscular activity confined to one muscle group;
      3 = visible muscular activity in more than one muscle group; and 4 = gross
      muscular activity involving the entire body. The emergence time from anesthesia,
      defined as the time between withdrawal of isoflurane and tracheal extubation, was
      documented. RESULTS: The number of patients with observable shivering was 19 in
      group P, nine in group G, seven in group T and six in group M. Granisetron
      significantly reduced the incidence of shivering in comparison with placebo (p =
      0.013). Although the frequency of shivering was higher with granisetron in
      comparison to tramadol and meperidine, it was not statistically significant (p >
      0.05). The number of patients with a shivering score of 2, 3 and 4 was
      significantly higher in group P compared with the other groups (p = 0.001). Both
      meperidine and tramadol caused a significantly prolonged emergence time (20.58 +/
      3.56 and 16.45 +/- 4.13 minutes, respectively) as opposed to granisetron (13.58
      +/- 3.41 minutes) and placebo (12.61 +/- 3.31 minutes). CONCLUSION: The
      prophylactic use of granisetron 40 microg/kg is as effective as meperidine (0.4
      mg/kg) and tramadol (0.1 mg/kg) in preventing postanesthetic shivering without
      prolonging the emergence time from anesthesia.

PMID- 19097964
TI  - Ultrasonic cardiac output monitor provides accurate measurement of cardiac output
      in recipients after liver transplantation.
AB  - BACKGROUND: The ultrasonic cardiac output monitor (USCOM; USCOM Pty. Ltd.,
      Sydney, NSW, Australia) has been accepted as a noninvasive device for measuring
      cardiac function in various clinical conditions. The present study aimed at
      comparing the accuracy of this device with that of the thermodilution technique
      in recipients in the early postoperative period after liver transplantation.
      METHODS: Fifteen mechanically ventilated patients were studied on the first
      postoperative day after liver transplantation. We compared the left-sided and
      right-sided cardiac output (CO) determined by USCOM with that obtained from the
      thermodilution technique with a pulmonary artery catheter every 8 hours in the
      intensive care unit. Each patient received a total of four paired measurements.
      Bland-Altman analysis was used for bias and precision testing. The CO measured by
      USCOM and the thermodilution method were considered interchangeable if the limits
      of agreement lay within +/- 1 L per minute or 20% of the mean CO. RESULTS: Forty
      eight paired left-sided CO measurements were obtained from 12 patients. Three
      patients were excluded due to unacceptable signals. Comparison of these two
      techniques revealed a bias of 0.13 L per minute and limits of agreement at -0.65
      L and 0.92 L per minute. Fifty-six paired right-sided CO measurements were
      obtained from 14 patients with one patient excluded due to an unobtainable
      optimal signal. A bias of 0.11 L per minute with limits of agreement at -0.51 L
      and 0.72 L per minute were found for these two techniques. CONCLUSION: This is
      the first study to evaluate the accuracy of USCOM in the post-liver transplant
      setting. This device is accurate in measuring CO in liver transplant recipients
      postoperatively. Possible risks of arrhythmia, infection and pulmonary artery
      rupture can be avoided because of its noninvasive nature. USCOM should be
      considered as an alternative in hemodynamic monitoring after liver
      transplantation.

PMID- 19097965
TI  - Clinical value of application of cerebral oximetry in total replacement of the
      aortic arch and concomitant vessels.
AB  - Cerebral ischemia or infarction caused by several equivocal mechanisms is a major
      complication after aortic arch replacement. Here, we report a 28-year-old male
      who underwent total replacement of the aortic arch and concomitant tributaries
      for hypoplasia of the transverse aortic arch and aortic branches. Continuous
      cerebral oxygen saturation (rSO2) monitoring was applied throughout the whole
      surgical course. According to the trend of rSO2, we could not only optimize the
      cerebral perfusion, but also confirm the patency of graft anastomosis. Therefore,
      monitoring rSO2 is very useful for determining cerebral perfusion during major
      surgery, especially in complicated repair of an aortic aneurysm, or replacement
      of the aortic arch and/or arch vessels.

PMID- 19097966
TI  - Acute coronary syndrome in cisatracurium-induced anaphylactic shock: Kounis
      syndrome.
AB  - In this case report, we describe a 70-year-old male patient who sustained Kounis
      syndrome induced by cisatracurium administration immediately following induction
      of general anesthesia. Acute coronary syndrome combined with anaphylactic shock,
      termed Kounis syndrome, should be investigated in percutaneous coronary
      intervention to solve this complex and life-threatening condition. A team effort
      by cardiologist and anesthesiologist is essential for successful resuscitation.
      In general, the incidence of an anaphylactic reaction to cisatracurium is low,
      but a high serum IgE level in combination with a positive skin prick test in our
      patient was strongly suggestive of cisatracurium-induced Kounis syndrome. In
      addition, a cross-reaction between cisatracurium and rocuronium is reported.

PMID- 19097967
TI  - Application of Pulse Contour Cardiac Output (PiCCO) system for adequate fluid
      management in a patient with severe reexpansion pulmonary edema.
AB  - We report a case of severe reexpansion pulmonary edema that occurred immediately
      after reinflation of a collapsed lung by rapid negative pressure drainage of
      prolonged malignant pleural effusion and pneumohemothorax. Although hemodynamic
      stability was difficult to maintain under aggressive treatment with inhalation of
      nitric oxide, inotropics and prostacyclin infusion, conventional pulmonary artery
      catheterization was not adequate for surveillance and adjustment of fluid
      therapy. For balancing the preload and the extent of pulmonary edema, pulse
      contour cardiac output monitoring using a single transpulmonary thermal dilution
      technique was applied to achieve optimal cardiac preload for organ perfusion and
      to prevent worsening of pulmonary edema from fluid overload.

PMID- 19097968
TI  - Spleen rupture after mitral valve replacement for infective endocarditis.
AB  - We present a case of splenic rupture as the cause of a sudden drop in blood
      pressure soon after mitral valve surgery for infective endocarditis. This case
      suggests that, in addition to more common causes of unstable vital signs after
      valvular surgery, such as cardiac tamponade or bleeding at the operation site,
      splenic rupture, although rare, should be considered in the differential
      diagnosis. This is particularly important in the case of infective endocarditis.

PMID- 19097969
TI  - Neurological impairment following myocardial ischemia associated with
      postoperative epidural analgesia.
AB  - Although epidural analgesia reduces the postoperative stress response and
      provides good pain relief for patients, potential complications associated with
      the technique may decrease its acceptability for some patients. We describe a 76
      year-old female who underwent surgery for carcinoma of the urinary tract.
      Postoperative epidural analgesia was performed at the postanesthesia care unit.
      Neither a repeat attempt nor accidental dural puncture was encountered during the
      procedure. Unfortunately, she sustained neurological impairment of the bilateral
      lower limbs following an episode of myocardial ischemia during the early
      postoperative period. When the neurological deficit was recognized following
      epidural anesthesia, poor puncture technique was the first to be blamed. In fact,
      a high level of sensory blockade could markedly decrease blood pressure and heart
      rate, particularly in the presence of hypovolemia, which might lead to impairment
      of coronary perfusion and result in myocardial ischemia. Severe systemic
      hypotension might further lead to hypoperfusion of the spinal cord, most possibly
      in the mid-thoracic region (T4 to T8) due largely to its relative
      hypovascularity. Therefore, we recommend that maintaining sufficient circulatory
      volume of the patient, evaluating and recording the neurological function of the
      patient and determining the possible risk factors associated with coronary
      arterial disease are imperative prior to performing an epidural procedure.

PMID- 19097970
TI  - Vaccination and urgent surgery in children: anesthetic concerns.

PMID- 19097971
TI  - Personalization of helping relationships: resident service coordinators' work
      with elderly residents.
AB  - As part of a larger study, in-depth interviews were conducted with 26 Resident
      Services Coordinators (RSCs) working in elderly housing to explore their
      experiences working with residents. Qualitative analysis revealed a major theme:
      RSCs view themselves as critical sources of support in residents' lives.
      Additionally, two subthemes reveal the affective nature of the relationships that
      RSCs form with residents: (a) Some RSCs working with elders report a very strong
      sense of obligation to familyless or isolated elders; and (b) in some instances,
      they describe their relationships with residents using family-like terms. Frail
      residents' limited access to support appears to strengthen the affective bond
      that some RSCs form with residents. The findings have implications for
      understanding how RSCs view their role and the emotional rewards and costs that
      RSCs experience in their role.

PMID- 19097972
TI  - The relationship of personal assistance service utilization to other Medicaid
      payments among working-age adults with disabilities.
AB  - This study examined changes in Medicaid provider payments prior to and following
      approval for personal assistance services (PAS) among 471 PAS users compared to
      295 nonusers who qualified for but did not use PAS, adjusting for differences
      between users and nonusers using propensity scores. PAS users showed a
      significantly greater increase in total monthly payments from pre- to post-PAS
      approval compared to nonusers (35% vs. -9) due to high average monthly payments
      for PAS ($1325). However, users showed a decrease in non-PAS payments compared to
      nonusers (1%-9% vs. -9%), with significant decreases in payments for both
      acute/rehabilitation hospitalizations and for nursing home/other long-term
      residential stays among users. While costly, savings in other areas may help
      reduce the net cost of PAS.

PMID- 19097973
TI  - Evaluating a multicomponent caregiver intervention.
AB  - There is compelling evidence that caring for an elderly individual with
      functional limitations is physically and psychologically stressful. The purpose
      of this study is to test a multimodal caregiver intervention of ethnically and
      racially diverse caregivers. We sought to examine if caregivers (n=199) of older
      adults with physical and/or cognitive problems experienced improved depression
      and caregiver outcomes after participating in a community-based Caregiver
      Support/Training Program (CS/TP). Using a single group pretest--post-test design,
      caregiver depression decreased significantly. Specifically, caregivers were more
      likely to report higher positive affect at post-test. Although caregivers
      reported decreased caregiver burden, the difference was not statistically
      significant. One-way ANOVAs were also conducted to look at group differences. The
      findings of this study will help practitioners understand the importance of
      developing more targeted interventions that take specific ethnic and cultural
      characteristics of caregivers into consideration.

PMID- 19097974
TI  - Effect of adding a virtual community (bulletin board) to smokefree.gov:
      randomized controlled trial.
AB  - BACKGROUND: Demand for online information and help exceeds most other forms of
      self-help. Web-assisted tobacco interventions (WATIs) offer a potentially low
      cost way to reach millions of smokers who wish to quit smoking and to test
      various forms of online assistance for use/utilization and user satisfaction.
      OBJECTIVES: Our primary aim was to determine the utilization of and satisfaction
      with 2 versions of a smoking cessation website (smokefree.gov), one of which
      included an asynchronous bulletin board (BB condition). A secondary goal was to
      measure changes in smoking behavior 3 months after enrollment in the study.
      METHODS: All participants were adult federal employees or contractors to the
      federal government who responded to an email and indicated a willingness to quit
      smoking in 30 days. We randomly assigned participants to either the BB condition
      or the publicly available version--usual care (UC)--and then assessed the number
      of minutes of website use and satisfaction with each condition as well as changes
      in smoking behavior. RESULTS: Among the 1375 participants, 684 were randomized to
      the BB intervention, and 691 to the control UC condition. A total of 39.7%
      returned a follow-up questionnaire after 3 months, with similar rates across the
      two groups (UC: n=279, 40.3%; BB: n=267, 39.0%). Among those respondents assigned
      to the BB condition, only 81 participants (11.8%) elected to view the bulletin
      board or post a message, limiting our ability to analyze the impact of bulletin
      board use on cessation. Satisfaction with the website was high and did not differ
      significantly between conditions (UC: 90.2%, BB: 84.9%, P= .08). Utilization, or
      minutes spent on the website, was significantly longer for the BB than the UC
      condition (18.0 vs 11.1, P = .01) and was nearly double for those who remained in
      the study (21.2) than for those lost to follow-up (9.6, P< .001). Similar
      differences were observed between those who made a serious quit attempt versus
      those who did not (22.4 vs 10.4, P= .02) and between those with a quit date on or
      a few days prior to the enrollment date versus those with a later quit date (29.4
      vs 12.5, P = .001). There were no statistically significant differences in quit
      rates between the BB and UC group, both in intent-to-treat analysis (ITT) and in
      analyzing the adherence subgroup (respondents) only. Combined across the UC and
      BB groups, 7-day abstinence was 6.8% with ITT and 17.6% using only participants
      in the follow-up (adherence). For participants who attempted to quit within a few
      days of study entry (vs 30 days), quit rates were 29.6% (ITT) and 44.4%
      (adherence). CONCLUSIONS: Quit rates for participants were similar to other
      WATIs, with the most favorable outcomes demonstrated by smokers ready to quit at
      the time of enrolling in the trial and smokers using pharmacotherapy. Utilization
      of the asynchronous bulletin board was lower than expected, and did not have an
      impact on outcomes (quit rates). Given the demand for credible online resources
      for smoking cessation, future studies should continue to evaluate use of and
      satisfaction with Web features and to clarify results in terms of time since last
      cigarette as well as use of pharmacotherapy.

PMID- 19097975
TI  - Patterns of use of an automated interactive personalized coaching program for
      smoking cessation.
AB  - BACKGROUND: The QuitCoach, an "expert system" program of tailored advice for
      smoking cessation developed in Australia, has been publicly available since July
      2003, albeit with limited promotion. The program is designed to be used on
      multiple occasions, guiding the user through the process of smoking cessation in
      the manner of a "life coach". Email reminders are sent at scheduled intervals to
      prompt optimal and repeated use. OBJECTIVES: The aims of this study were to
      characterize QuitCoach users and to determine what characteristics of smokers
      affect their participation over time. Of particular interest was whether users
      tend to return following a relapse and, thus, use the program as a tool for
      relapse prevention or recovery. We also explored patterns of change associated
      with returns to the site, whether prompted by reminder emails or not prompted at
      all. METHODS: Between July 2003 and June 2007, 28,247 individuals completed an
      initial assessment on the QuitCoach, of whom 83.7% (n = 23,656) registered. Data
      were collected during a 10-minute online questionnaire that all users completed
      in order to obtain tailored cessation advice. This included questions concerning
      basic demographic information, quitting history, current smoking status and
      cigarette consumption, stage of change, and use of pharmacotherapy. RESULTS: The
      median age of users was 34 years, and 62% were female. Most (96%) were current
      smokers. Overall, 91% were planning to quit in the next 30 days, and half (49.9%)
      had set a quit date. Those who had recently relapsed to smoking following a quit
      attempt made up 37%. Among registered users, 27% returned for a second visit, a
      median 9 days after their first. Overall, a third visit was completed by 11% and
      2% returned within 2 days. Women, older smokers, those who had recently quit, and
      those using pharmacotherapy were more likely to return. From the second visit on,
      most people who completed an assessment had quit. Likelihood of responding to a
      prompt to return was largely unrelated to user characteristics or cessation
      outcome. CONCLUSIONS: Internet-based programs have considerable potential to
      reach large numbers of smokers at low cost. The QuitCoach is attracting
      considerable use, with most using it to make a quit attempt and, for those who
      continue to use the QuitCoach, to help them stay quit. Nonetheless, most users
      only visited the site once, suggesting improved strategies are needed for
      encouraging repeated use.

PMID- 19097976
TI  - Renal screening in children after exposure to low dose melamine in Hong Kong:
      cross sectional study.
AB  - OBJECTIVE: To investigate the renal outcomes of children after exposure to low
      dose melamine in Hong Kong. DESIGN: Cross sectional study. SETTING: Special
      assessment centres, Hong Kong. PARTICIPANTS: 3170 children (1422 girls and 1748
      boys) aged 12 years or less referred from territory-wide primary care clinics
      after daily consumption for one month or more of milk products tainted with
      melamine. MAIN OUTCOME MEASURES: Presence of renal stones and haematuria.
      RESULTS: One child had a confirmed renal stone, seven were suspected of having
      melamine related renal deposits, and 208 (6.6%) were positive for blood in urine
      by reagent strip. A proportion of these children were followed up at the special
      assessment centre, but only 7.4% of those positive for blood on reagent strip
      were confirmed by microscopy, suggesting an overall estimated prevalence of less
      than 1% for microscopic haematuria. CONCLUSIONS: No severe adverse renal
      outcomes, such as acute renal failure or urinary tract obstruction, were detected
      in children after exposure to low dose melamine. Our results were similar to
      territory-wide findings in Hong Kong. Even including the seven children with
      suspected renal deposits, the prevalence of suspected melamine related
      abnormalities on ultrasonography was only 0.2%. None of these children required
      specific treatment. The prevalence of microscopic haematuria was probably
      overestimated by the reagent strip. These data suggest that large scale and
      urgent screening programmes may not be informative or cost effective for
      populations who have been exposed to low dose melamine.

PMID- 19097977
TI  - German experts cause controversy after calling for atomoxetine to be withdrawn.

PMID- 19097978
TI  - Researchers refine in vitro test that will reduce the risk of "first in humans"
      drug trials.

PMID- 19097980
TI  - Understanding the role of the doctor.

PMID- 19097981
TI  - Persistent inactivation of macrophage cyclooxygenase-2 in mycobacterial pulmonary
      inflammation.
AB  - The induction of cyclooxygenase-2 (COX-2) in tissue macrophages (MO) increases
      prostaglandin E(2) (PGE(2)) release, potentially down-regulating granulomatous
      inflammation. In response to Mycobacteria, local MO express COX-2, which is
      either nuclear envelope (NE)-associated or NE-dissociated. Persistent
      mycobacterial pulmonary inflammation is characterized by alveolar MO expressing
      NE-dissociated (inactive) COX-2 without release of PGE(2). In this study, we
      examined COX-2 in alveolar MO after intranasal exposure to heat-killed
      Mycobacterium bovis BCG (HK-BCG). After administration, whole lungs of C57Bl/6
      mice were lavaged with saline; COX-2 expression and PGE(2) release by alveolar MO
      and tumor necrosis factor (TNF)-alpha and nitric oxide levels in the lung lavage
      were monitored. Normal alveolar MO had undetectable levels of COX-2 on Western
      blots. However, 1 day after intranasal administration, almost all alveolar MO had
      phagocytosed HK-BCG and expressed NE-dissociated COX-2 without any increase in
      the release of PGE(2). At 28 days after intranasal administration, 68% of
      alveolar MO still contained both BCG and the NE-dissociated form of COX-2. NE
      associated (active) COX-2 was not observed in alveolar MO. In contrast, 7 days
      after intraperitoneal injection of HK-BCG, peritoneal MO containing HK-BCG were
      no longer detected. At 28 days after intranasal administration, TNF-alpha and
      nitrite levels in the lung lavage fluid were significantly higher than those in
      controls. Our results indicate that mycobacterial pulmonary inflammation is
      associated with suppressed PGE(2) production by alveolar MO, with expression of
      COX-2 dissociated from the NE.

PMID- 19097982
TI  - Effect of IL-10 on neutrophil recruitment and survival after Pseudomonas
      aeruginosa challenge.
AB  - IL-10 is a potent, endogenous anti-inflammatory cytokine known to decrease
      cytokine and keratinocyte-derived chemokine (KC) expression. Traditionally, in
      vivo effects of IL-10 were extrapolated from studies employing systemic antibody
      neutralization. As a result, divergent data regarding the protective and/or
      harmful roles of IL-10 have been reported. In this study, we used a lung
      specific, tetracycline-inducible IL-10 overexpression-transgenic (IL-10 OE) mouse
      to study the effects of IL-10 overexpression on Pseudomonas aeruginosa-induced
      lung inflammation and corresponding survival in mice. Overexpression of IL-10 in
      the lung significantly increased mortality. During the early phase after
      infection (6-hours after infection), neutrophil recruitment as well as cytokine
      (TNF-alpha) and chemokine (KC) expression were significantly decreased in the IL
      10 OE mice, which resulted in attenuated bacterial clearance. In contrast,
      overzealous production of KC and TNF-alpha intensified neutrophil infiltration
      and increased vascular leakage in IL-10 OE mice at the later stage of infection
      (24 hours after infection). Neutrophil depletion showed impaired bacterial
      clearance in both control and IL-10 OE mice, and further enhanced mouse
      mortality, whereas exogenous administration of KC reversed this finding. Our data
      indicate that early neutrophil recruitment is important for combating bacterial
      infection, and that the inhibition of neutrophil recruitment by IL-10 results in
      insufficient bacteria clearance in the lung, leading to excessive development of
      inflammation and increased mortality.

PMID- 19097983
TI  - Matrix metalloproteinase-9 deficiency worsens lung injury in a model of
      bronchopulmonary dysplasia.
AB  - Increased activity of matrix metalloproteinase (MMP)-9 is associated with the
      development of bronchopulmonary dysplasia (BPD) in newborn infants, but the role
      of MMP-9 in the pathophysiology of BPD is unclear. We have shown that perinatal
      expression of interleukin-1 beta (IL-1 beta) in the lung is sufficient to cause a
      BPD-like illness in infant mice. To study the hypothesis that MMP-9 is an
      important downstream mediator in IL-1 beta-induced lung injury in the newborn, we
      compared the effects of IL-1 beta on fetal and postnatal lung inflammation and
      development in transgenic mice with regulatable pulmonary overexpression of human
      mature IL-1 beta with wild-type (IL-1 beta/MMP-9(+/+)) or null (IL-1 beta/MMP-9(
      /-)) MMP-9 loci. IL-1 beta increased the expression of MMP-9 mRNA and amount of
      MMP-9 protein in the lungs of MMP-9(+/+) mice. IL-1 beta/MMP-9(-/-) mice had
      fewer neutrophils but more macrophages in the lungs than did IL-1 beta/MMP-9(+/+)
      mice. MMP-9 deficiency increased pulmonary cell death and macrophage clearance of
      dying cells in IL-1 beta-expressing mice. IL-1 beta/MMP-9(-/-) mice had more
      severe alveolar hypoplasia than IL-1 beta/MMP-9(+/+) mice, implying that IL-1
      beta-induced lung disease was worsened in the absence of MMP-9. These results
      suggest that MMP-9 activity in the inflamed neonatal lung protects the lung
      against injury.

PMID- 19097984
TI  - Alterations in gene expression in human mesothelial cells correlate with mineral
      pathogenicity.
AB  - Human mesothelial cells (LP9/TERT-1) were exposed to low and high (15 and 75
      microm(2)/cm(2) dish) equal surface area concentrations of crocidolite asbestos,
      nonfibrous talc, fine titanium dioxide (TiO2), or glass beads for 8 or 24 hours.
      RNA was then isolated for Affymetrix microarrays, GeneSifter analysis and QRT
      PCR. Gene changes by asbestos were concentration- and time-dependent. At low
      nontoxic concentrations, asbestos caused significant changes in mRNA expression
      of 29 genes at 8 hours and of 205 genes at 24 hours, whereas changes in mRNA
      levels of 236 genes occurred in cells exposed to high concentrations of asbestos
      for 8 hours. Human primary pleural mesothelial cells also showed the same
      patterns of increased gene expression by asbestos. Nonfibrous talc at low
      concentrations in LP9/TERT-1 mesothelial cells caused increased expression of 1
      gene Activating Transcription Factor 3 (ATF3) at 8 hours and no changes at 24
      hours, whereas expression levels of 30 genes were elevated at 8 hours at high
      talc concentrations. Fine TiO2 or glass beads caused no changes in gene
      expression. In human ovarian epithelial (IOSE) cells, asbestos at high
      concentrations elevated expression of two genes (NR4A2, MIP2) at 8 hours and 16
      genes at 24 hours that were distinct from those elevated in mesothelial cells.
      Since ATF3 was the most highly expressed gene by asbestos, its functional
      importance in cytokine production by LP9/TERT-1 cells was assessed using siRNA
      approaches. Results reveal that ATF3 modulates production of inflammatory
      cytokines (IL-1 beta, IL-13, G-CSF) and growth factors (VEGF and PDGF-BB) in
      human mesothelial cells.

PMID- 19097985
TI  - The antioxidant mimetic, MnTE-2-PyP, reduces intracellular growth of
      Mycobacterium abscessus.
AB  - Mycobacterium abscessus is a rapidly growing environmental mycobacterium that can
      cause severe skin, soft tissue, and lung infections. M. abscessus grows inside
      macrophages, and these cells release a vast number of proinflammatory cytokines
      in response to infections. The metalloporphyrin, MnTE-2-PyP, is a broad
      antioxidant that reduces inflammatory cell signaling. Macrophage-like THP-1 cells
      were infected with M. abscessus in the presence or absence of MnTE-2-PyP. MnTE-2
      PyP significantly decreased, in a dose-dependent manner, the number of M.
      abscessus organisms recovered from infected THP-1 cells 4 and 8 days after
      infection. Furthermore, when combined with clarithromycin, MnTE-2-PyP additively
      reduced the number of cells associated with M. abscessus. A mechanism of
      bacterial growth inhibition by MnTE-2-PyP was then elucidated. It was found that
      MnTE-2-PyP promoted the survival of infected THP-1 cells and increased fusion of
      M. abscessus-containing phagosomes with lysosomes.

PMID- 19097986
TI  - Effects of azithromycin on glutathione S-transferases in cystic fibrosis airway
      cells.
AB  - Anti-inflammatory properties of azithromycin (AZM) have been proposed as possible
      mechanisms of clinical beneficial effects in patients with cystic fibrosis (CF).
      Altered glutathione (GSH) transport in cystic fibrosis transmembrane regulator
      protein (CFTR)-deficient cells leads to the occurrence of oxidative stress that
      finally induces glutathione S-transferase (GST) activity. The present
      investigation was aimed to verify the effects of AZM on GST activity and
      expression in CF airway cells in vitro and in vivo. AZM exposure significantly
      decreased GSTT1 and GSTM1 mRNA and protein expression in IB3-1, restoring the
      levels to those observed in non-CF C38 cells, which also express lower levels of
      gamma-glutamyltransferase (GGT) activity than IB3-1. In another CF cell line,
      2CFSMEo-, AZM produced 45% reduction in GSTT1 and GSTM1 mRNA levels. AZM reduced
      GST activity by approximately 25% and 40% in IB3-1 and 2CFSMEo- cells,
      respectively. GSTP1 was similarly expressed in all CF and non-CF cells and was
      unaffected by AZM. The anti-inflammatory cytokine IL-10 down-modulated GST
      activity at similar levels, supporting a link between GST inhibition and anti
      inflammatory properties of AZM. In bronchoalveolar lavage fluid of CF mice
      homozygous for the F508 del mutation, GSTM1 protein levels were undetectable
      after AZM treatment. The association between increased GST expression and
      activity, together with its reversal by AZM treatment in vitro and in vivo,
      suggest novel antioxidant properties for this drug. The issue whether decreased
      GST activity may directly concur to anti-inflammatory properties of AZM or is
      rather a marker of the oxidative status of CF cells will require additional
      studies.

PMID- 19097987
TI  - Carbon monoxide modulates alpha-smooth muscle actin and small proline rich-1a
      expression in fibrosis.
AB  - Carbon monoxide (CO) is a biologically active molecule produced in the body by
      the stress-inducible enzyme, heme oxygenase. We have previously shown that CO
      suppresses fibrosis in a murine bleomycin model. To investigate the mechanisms by
      which CO opposes fibrogenesis, we performed gene expression profiling of
      fibroblasts treated with transforming growth factor-beta(1) and CO. The most
      highly differentially expressed categories of genes included those related to
      muscular system development and the small proline-rich family of proteins. We
      confirmed in vitro, and in an in vivo bleomycin model of lung fibrosis, that CO
      suppresses alpha-smooth muscle actin expression and enhances small proline-rich
      protein-1a expression. We further show that these effects of CO depend upon
      signaling via the extracellular signal-regulated kinase pathway. Our results
      demonstrate novel transcriptional targets for CO and further elucidate the
      mechanism by which CO suppresses fibrosis.

PMID- 19097989
TI  - Intrapulmonary delivery of XCL1-targeting small interfering RNA in mice
      chronically infected with Mycobacterium tuberculosis.
AB  - Mice infected for 60 days with Mycobacterium tuberculosis were treated with
      aerosolized XCL1-targeting small interfering RNA (siRNA) to induce local and
      transient suppression of XCL1/lymphotactin (an important chemokine in tuberculoid
      granuloma formation). The local pulmonary siRNA therapy resulted in a 50%
      decrease in the total amount of xcl1 gene transcripts at 3 days, and 40 to 50%
      protein suppression 3 and 5 days after treatment. Reduced XCL1 expression in the
      lungs was associated with decreased numbers of T lymphocytes, reduction in the
      IFN-gamma response, disorganized granulomatous lesions, and higher fibrosis when
      compared with control mice treated with either PBS or nontargeting siRNA. This
      indicates that a transient but strong modulation of the production of XCL1 in the
      lungs has a significant effect on the influx of IFN-gamma-secreting T cells, as
      well as local pathology, but without significantly altering containment of the
      infection.

PMID- 19097988
TI  - Nickel mobilizes intracellular zinc to induce metallothionein in human airway
      epithelial cells.
AB  - We recently reported that induction of metallothionein (MT) was critical in
      limiting nickel (Ni)-induced lung injury in intact mice. Nonetheless, the
      mechanism by which Ni induces MT expression is unclear. We hypothesized that the
      ability of Ni to mobilize zinc (Zn) may contribute to such regulation and
      therefore, we examined the mechanism for Ni-induced MT2A expression in human
      airway epithelial (BEAS-2B) cells. Ni induced MT2A transcript levels and protein
      expression by 4 hours. Ni also increased the activity of a metal response element
      (MRE) promoter luciferase reporter construct, suggesting that Ni induces MRE
      binding of the metal transcription factor (MTF-1). Exposure to Ni resulted in the
      nuclear translocation of MTF-1, and Ni failed to induce MT in mouse embryonic
      fibroblasts lacking MTF-1. As Zn is the only metal known to directly bind MTF-1,
      we then showed that Ni increased a labile pool of intracellular Zn in cells as
      revealed by fluorescence-activated cell sorter using the Zn-sensitive
      fluorophore, FluoZin-3. Ni-induced increases in MT2A mRNA and MRE-luciferase
      activity were sensitive to the Zn chelator, TPEN, supporting an important role
      for Zn in mediating the effect of Ni. Although neither the source of labile Zn
      nor the mechanism by which Ni liberates labile Zn was apparent, it was noteworthy
      that Ni increased intracellular reactive oxygen species (ROS). Although both N
      acetyl cysteine (NAC) and ascorbic acid (AA) decreased Ni-induced increases in
      ROS, only NAC prevented Ni-induced increases in MT2A mRNA, suggesting a special
      role for interactions of Ni, thiols, and Zn release.

PMID- 19097990
TI  - Nicotine activates and up-regulates nicotinic acetylcholine receptors in
      bronchial epithelial cells.
AB  - Prenatal nicotine exposure impairs normal lung development and leads to
      diminished pulmonary function after birth. Previous work from our laboratory has
      demonstrated that nicotine alters lung development by affecting a nonneuronal
      cholinergic autocrine loop that is expressed in lung. Bronchial epithelial cells
      (BECs) express choline acetyltransferase, the choline high-affinity transporter
      and nicotinic acetylcholine (ACh) receptor (nAChR) subunits. We now demonstrate
      through a combination of morphological and electrophysiological techniques that
      nicotine affects this autocrine loop by up-regulating and activating cholinergic
      signaling. RT-PCR showed the expression of alpha 3, alpha 4, alpha 7, alpha 9,
      alpha 10, beta2, and beta 4 nAChR mRNAs in rhesus monkey lung and cultured BECs.
      The expression of alpha 7, alpha 4, and beta2 nAChR was confirmed by
      immunofluorescence in the cultured BECs and lung. The electrophysiological
      characteristics of nAChR in BECs were determined using whole-cell patch-clamp on
      cultured BECs. Both ACh and nicotine evoked an inward current, with a rapid
      desensitizing current. Nicotine induced inward currents in a concentration
      dependent manner, with an EC(50) of 26.7 microM. Nicotine-induced currents were
      reversibly blocked by the nicotinic antagonists, mecamylamine, dihydro-beta
      erythroidine, and methyllcaconitine. Incubation of BECs with 1 microM nicotine
      for 48 hours enhanced nicotine-induced currents by roughly 26%. The protein
      tyrosine phosphorylation inhibitor, genistein, increased nicotine-induced
      currents by 58% and enhanced methyllcaconitine-sensitive currents (alpha 7 nAChR
      activities) 2.3-fold, whereas the protein tyrosine phosphatase inhibitor,
      pervanadate, decreased the effects of nicotine. These results demonstrate that
      chronic nicotine exposure up-regulates nAChR activity in developing lung, and
      that nAChR activity can be further modified by tyrosine phosphorylation.

PMID- 19097991
TI  - High-mobility group box 1 contributes to lethality of endotoxemia in heme
      oxygenase-1-deficient mice.
AB  - High-mobility group box 1 (HMGB1) is a nuclear protein that has been found to be
      a critical mediator of lethality in endotoxemia and sepsis. During the systemic
      inflammatory response, circulating levels of HMGB1 are increased, but in a
      delayed fashion compared with early inflammatory mediators. To counteract the
      inflammatory response of endotoxemia, a secondary anti-inflammatory response
      ensues in an attempt to prevent inflammation-induced tissue injury. One such
      cytoprotective gene that is induced during endotoxemia is heme oxygenase (HO)-1.
      HO-1, and its products of heme metabolism, possess anti-inflammatory and
      antioxidant properties to counter the damaging effects of endotoxemia. In the
      present study, we wanted to determine whether tissue and circulating levels of
      HMGB1 are increased further in the absence of HO-1 during endotoxemia, and
      whether this increase may contribute to the pathobiology of endotoxemia. Lung
      inflammation, HMGB1 protein levels, and expression of HMGB1 in inflammatory cells
      were increased in HO-1(-/-) mice compared with HO-1+/+ mice. After the
      administration of LPS, tissue levels of HMGB1 were not increased further in HO-1(
      /-) mice; however, circulating levels of HMGB1 were higher when compared with HO
      1+/+ mice. HO-1(-/-) mice treated with a carbon monoxide-releasing molecule or
      biliverdin showed a reduction in plasma HMGB1, which was associated with a marked
      improvement in survival. HO-1(-/-) mice given HMGB1-neutralizing antibody showed
      improvement in survival compared with control antibody. These data suggest that
      exaggerated circulating levels of HMGB1 contribute to endotoxin-induced mortality
      in the absence of HO-1.

PMID- 19097993
TI  - CD4-anchoring HIV-1 fusion inhibitor with enhanced potency and in vivo stability.
AB  - In this study, we describe a novel CD4-targeting bifunctional human
      immunodeficiency virus (HIV-1) fusion inhibitor (CD4-BFFI) that blocks HIV-1
      entry by inhibiting both HIV-1 attachment and fusion and is highly potent against
      both R5 and X4 HIV-1 viruses in various antiviral assays, including peripheral
      blood mononuclear cell (PBMC) infection assays. Previously, we have reported a
      CCR5 antibody-based bifunctional HIV-1 fusion inhibitor (BFFI) that was highly
      active in blocking R5 HIV-1 infection but was ineffective against X4 viruses
      infecting human PBMCs (Kopetzki, E., Jekle, A., Ji, C., Rao, E., Zhang, J.,
      Fischer, S., Cammack, N., Sankuratri, S., and Heilek, G. (2008) Virology J. 5, 56
      65). CD4-BFFI, which consists of two HIV-1 fusion inhibitor (FI) T-651 variant
      peptides recombinantly fused to the Fc end of a humanized anti-CD4 monoclonal
      antibody, has demonstrated more than 100-fold greater antiviral activity than T
      651 variant or the parental CD4 monoclonal antibody. Mechanistic studies revealed
      that CD4-BFFI primarily blocks the HIV-1-cell fusion step through its FI peptide
      moieties. The enhanced antiviral activity of CD4-BFFI is most likely due to avid
      binding of the bivalent FI peptides as well as the increased local concentration
      of CD4-BFFI via attachment to the target cell surface receptor CD4. In vivo
      pharmacokinetic studies demonstrated that CD4-BFFI was stable in monkey blood,
      and a dose of 10 mg/kg maintained serum concentrations greater than 2,000-fold
      over the IC(90) value for 7 days postdosing. This novel bifunctional inhibitor
      with improved potency and favorable pharmacokinetic properties may offer a novel
      approach for HIV-1 therapy.

PMID- 19097992
TI  - Bcl-2 family proteins contribute to apoptotic resistance in lung cancer
      multicellular spheroids.
AB  - Combinatorial therapies using the proteasome inhibitor, bortezomib, have been
      found to induce synergistic apoptosis in cancer cells grown as monolayers;
      however, three-dimensional spheroid culture may be a better model for the
      multicellular resistance found in solid tumors, such as lung cancer. We tested
      the combinatorial apoptotic strategy of using bortezomib together with TNF
      related apoptosis-inducing ligand (TRAIL), both in monolayers and in spheroids of
      A549 lung cancer cells. Indeed, bortezomib plus TRAIL induced synergistic
      apoptosis in A549 cells grown as monolayers, but had little effect on A549 cells
      grown as three-dimensional multicellular spheroids. The acquired resistance of
      spheroids was not due to a limitation of diffusion, to survival pathways, such as
      NF-kappaB or PI3K/Akt/mTOR, or to the up-regulation of FLIP(S) (Fas-associated
      death domain-like IL-1 beta-converting enzyme inhibitory protein, short). We then
      investigated a role for the Bcl-2 family of anti- and proapoptotic proteins. When
      cells formed spheroids, antiapoptotic Bcl-2 increased, whereas antiapoptotic Mcl
      1 decreased. ABT-737, a small molecule that inhibits Bcl-2, but not Mcl-1,
      abolished the multicellular resistance of A549 spheroids to bortezomib plus
      TRAIL. In another lung cancer cell line, H1299, acquisition of multicellular
      resistance in spheroids was also accompanied by an increase in Bcl-2 and decrease
      in Mcl-1. In H1299 spheroids compared with those of A549, however, Mcl-1 remained
      higher, and Mcl-1 knockdown was more effective than ABT-737 in removing
      multicellular resistance. Our study suggests that the balance of Bcl-2 family
      proteins contributes to the acquired multicellular resistance of spheroids, and
      suggests a possible target for improving the response of lung cancer to
      bortezomib therapies.

PMID- 19097994
TI  - Purinergic P2X7 receptors mediate ATP-induced saliva secretion by the mouse
      submandibular gland.
AB  - Salivary glands express multiple isoforms of P2X and P2Y nucleotide receptors,
      but their in vivo physiological roles are unclear. P2 receptor agonists induced
      salivation in an ex vivo submandibular gland preparation. The nucleotide
      selectivity sequence of the secretion response was BzATP >> ATP > ADP >> UTP, and
      removal of external Ca(2+) dramatically suppressed the initial ATP-induced fluid
      secretion ( approximately 85%). Together, these results suggested that P2X
      receptors are the major purinergic receptor subfamily involved in the fluid
      secretion process. Mice with targeted disruption of the P2X(7) gene were used to
      evaluate the role of the P2X(7) receptor in nucleotide-evoked fluid secretion.
      P2X(7) receptor protein and BzATP-activated inward cation currents were absent,
      and importantly, purinergic receptor agonist-stimulated salivation was suppressed
      by more than 70% in submandibular glands from P2X(7)-null mice. Consistent with
      these observations, the ATP-induced increases in [Ca(2+)](i) were nearly
      abolished in P2X(7)(-/-) submandibular acinar and duct cells. ATP appeared to
      also act through the P2X(7) receptor to inhibit muscarinic-induced fluid
      secretion. These results demonstrate that the ATP-sensitive P2X(7) receptor
      regulates fluid secretion in the mouse submandibular gland.

PMID- 19097995
TI  - SWI/SNF regulates the cellular response to hypoxia.
AB  - Hypoxia induces a variety of cellular responses such as cell cycle arrest,
      apoptosis, and autophagy. Most of these responses are mediated by the hypoxia
      inducible factor-1alpha. To induce target genes, hypoxia-inducible factor-1alpha
      requires a chromatin environment conducive to allow binding to specific
      sequences. Here, we have studied the role of the chromatin-remodeling complex
      SWI/SNF in the cellular response to hypoxia. We find that SWI/SNF is required for
      several of the cellular responses induced by hypoxia. Surprisingly, hypoxia
      inducible factor-1alpha is a direct target of the SWI/SNF chromatin-remodeling
      complex. SWI/SNF components are found associated with the hypoxia-inducible
      factor-1alpha promoter and modulation of SWI/SNF levels results in pronounced
      changes in hypoxia-inducible factor-1alpha expression and its ability to
      transactivate target genes. Furthermore, impairment of SWI/SNF function renders
      cells resistant to hypoxia-induced cell cycle arrest. These results reveal a
      previously uncharacterized dependence of hypoxia signaling on the SWI/SNF complex
      and demonstrate a new level of control over the hypoxia-inducible factor-1alpha
      system.

PMID- 19097996
TI  - HCLK2 is required for activity of the DNA damage response kinase ATR.
AB  - ATR is a protein kinase that orchestrates the cellular response to replication
      problems and DNA damage. HCLK2 has previously been reported to stabilize ATR and
      Chk1. Here we provide evidence that human HCLK2 acts at an early step in the ATR
      signaling pathway and contributes to full-scale activation of ATR kinase
      activity. We show that HCLK2 forms a complex with ATR-ATRIP and the ATR activator
      TopBP1. We demonstrate that HCLK2-induced ATR kinase activity toward substrates
      requires TopBP1 and vice versa and provides evidence that HCLK2 facilitates
      efficient ATR-TopBP1 association. Consistent with its role in ATR activation,
      HCLK2 depletion severely impaired phosphorylation of multiple ATR targets
      including Chk1, Nbs1, and Smc1 after DNA damage. We show that HCLK2 is required
      for and stimulates ATR autophosphorylation and activity toward different
      substrates in vitro. Furthermore, HCLK2 depletion abrogated the G(2) checkpoint
      and decreased survival of cells after exposure to DNA damaging agents and
      replicative stress. Overall, our data suggest that HCLK2 facilitates ATR
      activation and, therefore, contributes to ATR-mediated checkpoint signaling.
      Importantly, our results suggest that HCLK2 functions in the same pathway as
      TopBP1 but that the two proteins regulate different steps in ATR activation.

PMID- 19097997
TI  - Molecular mechanisms of yeast cell wall glucan remodeling.
AB  - Yeast cell wall remodeling is controlled by the equilibrium between glycoside
      hydrolases, glycosyltransferases, and transglycosylases. Family 72 glycoside
      hydrolases (GH72) are ubiquitous in fungal organisms and are known to possess
      significant transglycosylase activity, producing elongated beta(1-3) glucan
      chains. However, the molecular mechanisms that control the balance between
      hydrolysis and transglycosylation in these enzymes are not understood. Here we
      present the first crystal structure of a glucan transglycosylase, Saccharomyces
      cerevisiae Gas2 (ScGas2), revealing a multidomain fold, with a (betaalpha)(8)
      catalytic core and a separate glucan binding domain with an elongated, conserved
      glucan binding groove. Structures of ScGas2 complexes with different beta-glucan
      substrate/product oligosaccharides provide "snapshots" of substrate binding and
      hydrolysis/transglycosylation giving the first insights into the mechanisms these
      enzymes employ to drive beta(1-3) glucan elongation. Together with mutagenesis
      and analysis of reaction products, the structures suggest a "base occlusion"
      mechanism through which these enzymes protect the covalent protein-enzyme
      intermediate from a water nucleophile, thus controlling the balance between
      hydrolysis and transglycosylation and driving the elongation of beta(1-3) glucan
      chains in the yeast cell wall.

PMID- 19097998
TI  - Cdc42-mTOR signaling pathway controls Hes5 and Pax6 expression in retinoic acid
      dependent neural differentiation.
AB  - The conditional knockout of the small GTPase Cdc42 from neuroepithelial (NE) and
      radial glial (RG) cells in the mouse telencephalon has been shown to have a
      significant impact on brain development by causing these neural progenitor cells
      to detach from the apical/ventricular surface and to lose their cell identity.
      This has been attributed to the requirement for Cdc42 in establishing proper
      apical/basal cell polarity and cell-cell adhesions. In the present study, we
      provide new insights into the role played by Cdc42 in the maintenance of neural
      progenitor cells, using the mouse embryonal carcinoma P19 cell line as a model
      system. We show that the ability of P19 cells to undergo the transition from an
      Oct3/4-positive, undifferentiated status to microtubule-associated protein 2
      positive neurons and glial fibrillary acidic protein-positive astrocytes, upon
      treatment with retinoic acid (RA), requires RA-induced activation of Cdc42 during
      the neural cell lineage specification phase. Experiments using chemical
      inhibitors and RNA interference suggest that the actions of Cdc42 are mediated
      through signaling pathways that start with fibroblast growth factors and
      Delta/Notch proteins and lead to Cdc42-dependent mTOR activation, culminating in
      the up-regulation of Hes5 and Pax6, two transcription factors that are essential
      for the maintenance of NE and RG cells. The constitutively active Cdc42(F28L)
      mutant was sufficient to up-regulate Hes5 and Pax6 in P19 cells, even in the
      absence of RA treatment, ultimately promoting their transition to neural
      progenitor cells. The ectopic Cdc42 expression also significantly augmented the
      RA-dependent up-regulation of these transcription factors, resulting in P19 cells
      maintaining their neural progenitor status but being unable to undergo terminal
      differentiation. These findings shed new light on how Cdc42 influences neural
      progenitor cell fate by regulating gene expression.

PMID- 19097999
TI  - Translational regulation of the human achaete-scute homologue-1 by fragile X
      mental retardation protein.
AB  - Fragile X syndrome is a common inherited cause of mental retardation that results
      from loss or mutation of the fragile X mental retardation protein (FMRP). In this
      study, we identified the mRNA of the basic helix-loop-helix transcription factor
      human achaete-scute homologue-1 (hASH1 or ASCL1), which is required for normal
      development of the nervous system and has been implicated in the formation of
      neuroendocrine tumors, as a new FMRP target. Using a double-immunofluorescent
      staining technique we detected an overlapping pattern of both proteins in the
      hippocampus, temporal cortex, subventricular zone, and cerebellum of newborn
      rats. Forced expression of FMRP and gene silencing by small interference RNA
      transfection revealed a positive correlation between the cellular protein levels
      of FMRP and hASH1. A luciferase reporter construct containing the 5'-untranslated
      region of hASH1 mRNA was activated by the full-length FMRP, but not by naturally
      occurring truncated FMR proteins, in transient co-transfections. The responsible
      cis-element was mapped by UV-cross-linking experiments and reporter mutagenesis
      assays to a (U)(10) sequence located in the 5'-untranslated region of the hASH1
      mRNA. Sucrose density gradient centrifugation revealed that hASH1 transcripts
      were translocated into a translationally active polysomal fraction upon transient
      transfection of HEK293 cells with FMRP, thus indicating translational activation
      of hASH1 mRNA. In conclusion, we identified hASH1 as a novel downstream target of
      FMRP. Improved translation efficiency of hASH1 mRNA by FMRP may represent an
      important regulatory switch in neuronal differentiation.

PMID- 19098000
TI  - The Akt/mTOR pathway assures the synthesis of HIF-1alpha protein in a glucose-
      and reoxygenation-dependent manner in irradiated tumors.
AB  - Transcriptional activity of HIF-1 (hypoxia-inducible factor-1) has been reported
      to be up-regulated in solid tumors after ionizing radiation; however, the
      molecular mechanism underlying the response remains to be elucidated. In the
      present study, we performed a series of molecular imaging experiments using a HIF
      1-dependent reporter gene, 5HREp-ODD-luc, and found an essential role of the
      Akt/mTOR pathway. Hypoxic tumor cells distant from blood vessels were
      dramatically reoxygenated at 24 h postirradiation, and HIF-1 activity increased
      as HIF-1alpha accumulated in the reoxygenated regions. The accumulation was
      inhibited with a nonmetabolizable glucose analog, 2-deoxy-d-glucose, through the
      suppression of radiation-induced phosphorylation of Akt in the reoxygenated
      regions. Akt knockdown and an mTOR inhibitor revealed the importance of the
      Akt/mTOR pathway in the postirradiation accumulation of HIF-1alpha. In vitro
      experiments confirmed that an increase in glucose availability induced Akt
      phosphorylation under reoxygenated conditions and consequently up-regulated HIF
      1alpha translation. Moreover, both the accelerated translation and the previously
      reported reactive oxygen species-mediated stabilization of HIF-1alpha protein
      were essential to the activation of HIF-1. All of these results indicate that
      Akt/mTOR-dependent translation of HIF-1alpha plays a critical role in the
      postirradiation up-regulation of intratumoral HIF-1 activity in response to
      radiation-induced alterations of glucose and oxygen availability in a solid
      tumor.

PMID- 19098001
TI  - Humanized Mouse Model of Cooley's Anemia.
AB  - A novel humanized mouse model of Cooley's Anemia (CA) was generated by targeted
      gene replacement in embryonic stem (ES) cells. Because the mouse does not have a
      true fetal hemoglobin, a delayed switching human gamma to beta(0) globin gene
      cassette (gammabeta(0)) was inserted directly into the murine beta globin locus
      replacing both adult mouse beta globin genes. The inserted human beta(0) globin
      allele has a mutation in the splice donor site that produces the same aberrant
      transcripts in mice as described in human cells. No functional human beta globin
      polypeptide chains are produced. Heterozygous gammabeta(0) mice suffer from
      microcytic anemia. Unlike previously described animal models of beta thalassemia
      major, homozygous gammabeta(0) mice switch from mouse embryonic globin chains to
      human fetal gamma globin during fetal life. When bred with human alpha globin
      knockin mice, homozygous CA mice survive solely upon human fetal hemoglobin at
      birth. This preclinical animal model of CA can be utilized to study the
      regulation of globin gene expression, synthesis, and switching; the reactivation
      of human fetal globin gene expression; and the testing of genetic and cell-based
      therapies for the correction of thalassemia.

PMID- 19098002
TI  - Selective inhibition of carotenoid cleavage dioxygenases: phenotypic effects on
      shoot branching.
AB  - Members of the carotenoid cleavage dioxygenase family catalyze the oxidative
      cleavage of carotenoids at various chain positions, leading to the formation of a
      wide range of apocarotenoid signaling molecules. To explore the functions of this
      diverse enzyme family, we have used a chemical genetic approach to design
      selective inhibitors for different classes of carotenoid cleavage dioxygenase. A
      set of 18 arylalkyl-hydroxamic acids was synthesized in which the distance
      between an iron-chelating hydroxamic acid and an aromatic ring was varied; these
      compounds were screened as inhibitors of four different enzyme classes, either in
      vitro or in vivo. Potent inhibitors were found that selectively inhibited enzymes
      that cleave carotenoids at the 9,10 position; 50% inhibition was achieved at
      submicromolar concentrations. Application of certain inhibitors at 100 microm to
      Arabidopsis node explants or whole plants led to increased shoot branching,
      consistent with inhibition of 9,10-cleavage.

PMID- 19098003
TI  - Somatic mutations of ErbB4: selective loss-of-function phenotype affecting signal
      transduction pathways in cancer.
AB  - Cancer drugs targeting ErbB receptors, such as epidermal growth factor receptor
      and ErbB2, are currently in clinical use. However, the role of ErbB4 as a
      potential cancer drug target has remained controversial. Recently, somatic
      mutations altering the coding region of ErbB4 were described in patients with
      breast, gastric, colorectal, or non-small cell lung cancer, but the functional
      significance of these mutations is unknown. Here we demonstrate that 2 of 10 of
      the cancer-associated mutations of ErbB4 lead to loss of ErbB4 kinase activity
      due to disruption of functionally important structural features. Interestingly,
      the kinase-dead ErbB4 mutants were as efficient as wild-type ErbB4 in forming a
      heterodimeric neuregulin receptor with ErbB2 and promoting phosphorylation of
      Erk1/2 and Akt in an ErbB2 kinase-dependent manner. However, the mutant ErbB4
      receptors failed to phosphorylate STAT5 and suppressed differentiation of MDA-MB
      468 mammary carcinoma cells. These findings suggest that the somatic ErbB4
      mutations have functional consequences and lead to selective changes in ErbB4
      signaling.

PMID- 19098004
TI  - Inhibition of neuronal nicotinic acetylcholine receptor subtypes by alpha
      Conotoxin GID and analogues.
AB  - alpha-Conotoxins are small disulfide-rich peptides from the venom of the Conus
      species that target the nicotinic acetylcholine receptor (nAChR). They are
      valuable pharmacological tools and also have potential therapeutic applications
      particularly for the treatment of chronic pain. alpha-Conotoxin GID is isolated
      from the venom of Conus geographus and has an unusual N-terminal tail sequence
      that has been shown to be important for binding to the alpha4beta2 subtype of the
      nAChR. To date, only four conotoxins that inhibit the alpha4beta2 subtype have
      been characterized, but they are of considerable interest as it is the most
      abundant nAChR subtype in the mammalian brain and has been implicated in a range
      of diseases. In this study, analysis of alanine-scan and truncation mutants of
      GID reveals that a conserved proline in alpha-conotoxins is important for
      activity at the alpha7, alpha3beta2, and alpha4beta2 subtypes. Although the
      proline residue was the most critical residue for activity at the alpha3beta2
      subtype, Asp(3), Arg(12), and Asn(14) are also critical at the alpha7 subtype.
      Interestingly, very few of the mutations tested retained activity at the
      alpha4beta2 subtype indicating a tightly defined binding site. This lack of
      tolerance to sequence variation may explain the lack of selective ligands
      discovered for the alpha4beta2 subtype to date. Overall, our findings contribute
      to the understanding of the structure-activity relationships of alpha-conotoxins
      and may be beneficial for the ongoing attempts to exploit modulators of the
      neuronal nAChRs as therapeutic agents.

PMID- 19098005
TI  - Regulation of reactive oxygen species homeostasis by peroxiredoxins and c-Myc.
AB  - Peroxiredoxins (Prxs) are highly conserved proteins found in most organisms,
      where they function primarily to scavenge reactive oxygen species (ROS). Loss of
      the most ubiquitous member of the family, Prx1, is associated with the
      accumulation of oxidatively damaged DNA and a tumor-prone phenotype. Prx1
      interacts with the transcriptional regulatory domain of the c-Myc oncoprotein and
      suppresses its transforming activity. The DNA damage in tissues of prx1-/- mice
      is associated in some cases with only modest increases in total ROS levels.
      However, these cells show dramatic increases in nuclear ROS and reduced levels of
      cytoplasmic ROS, which explains their mutational susceptibility. In the current
      work, we have investigated whether changes in other ROS scavengers might account
      for the observed ROS redistribution pattern in prx1-/- cells. We show
      approximately 5-fold increases in Prx5 levels in prx1-/- embryo fibroblasts
      relative to prx1+/+ cells. Moreover, Prx5 levels normalize when Prx1 expression
      is restored. Prx5 levels also appear to be highly dependent on c-Myc, and
      chromatin immunoprecipitation experiments showed differential occupancy of c-Myc
      and Prx1 complexes at E-box elements in the prx5 gene proximal promoter. This
      study represents a heretofore unreported mechanism for the c-Myc-dependent
      regulation of one Prx family member by another and identifies a novel means by
      which cells reestablish ROS homeostasis when one of these family members is
      compromised.

PMID- 19098006
TI  - Annular protofibrils are a structurally and functionally distinct type of amyloid
      oligomer.
AB  - Amyloid oligomers are believed to play causal roles in several types of amyloid
      related neurodegenerative diseases. Several different types of amyloid oligomers
      have been reported that differ in morphology, size, or toxicity, raising the
      question of the pathological significance and structural relationships between
      different amyloid oligomers. Annular protofibrils (APFs) have been described in
      oligomer preparations of many different amyloidogenic proteins and peptides as
      ring-shaped or pore-like structures. They are interesting because their pore-like
      morphology is consistent with numerous reports of membrane-permeabilizing
      activity of amyloid oligomers. Here we report the preparation of relatively
      homogeneous preparations of APFs and an antiserum selective for APFs (alphaAPF)
      compared with prefibrillar oligomers (PFOs) and fibrils. PFOs appear to be
      precursors for APF formation, which form in high yield after exposure to a
      hydrophobic-hydrophilic interface. Surprisingly, preformed APFs do not
      permeabilize lipid bilayers, unlike the precursor PFOs. APFs display a
      conformation-dependent, generic epitope that is distinct from that of PFOs and
      amyloid fibrils. Incubation of PFOs with phospholipids vesicles results in a loss
      of PFO immunoreactivity with a corresponding increase in alphaAPF
      immunoreactivity, suggesting that lipid vesicles catalyze the conversion of PFOs
      into APFs. The annular anti-protofibril antibody also recognizes heptameric alpha
      hemolysin pores, but not monomers, suggesting that the antibody recognizes an
      epitope that is specific for a beta barrel structural motif.

PMID- 19098008
TI  - The essential role of p53 in hyperpigmentation of the skin via regulation of
      paracrine melanogenic cytokine receptor signaling.
AB  - Hyperpigmentation of the skin is characterized by increases in melanin synthesis
      and deposition. Although considered a significant psychosocial distress, little
      is known about the detailed mechanisms of hyperpigmentation. Recently, the tumor
      suppressor protein p53 has been demonstrated to promote ultraviolet B-induced
      skin pigmentation by stimulating the transcription of a melanogenic cytokine,
      POMC (pro-opiomelanocortin), in keratinocytes. Given that p53 can be activated by
      various kinds of diverse stresses, including sun exposure, inflammation, and
      aging, this finding led us to examine the involvement of p53 in cytokine receptor
      signaling, which might result in skin hyperpigmentation. Immunohistochemical and
      reverse transcription-PCR analyses revealed the increased expression and
      phosphorylation of p53 in the epidermis of hyperpigmented spots, accompanied by
      the higher expression of melanogenic cytokines, including stem cell factor,
      endothelin-1, and POMC. The involvement of p53 in hyperpigmentation was also
      indicated by the significantly higher expression of p53 transcriptional targets
      in the epidermis of hyperpigmented spots. Treatment of human keratinocytes and
      melanocytes with known p53 activators or inhibitors, including pifithrin-alpha
      (PFT), demonstrated significant increases or decreases, respectively, in the
      expression of melanogenic factors, including cytokines and their receptors.
      Additionally, PFT administration abolished stem cell factor-induced
      phosphorylation of mitogen-activated protein kinase in human melanocytes.
      Furthermore, when organ-cultured hyperpigmented spots, in vitro human skin
      substitutes, and mouse skin were treated with PFT or p53 small interfering RNA,
      the expression of melanogenic cytokines and their receptors was significantly
      decreased, as were levels of tyrosinase and melanogenesis. Taken together, these
      data reveal the essential role of p53 in hyperpigmentation of the skin via the
      regulation of paracrine-cytokine signaling, both in keratinocytes and in
      melanocytes.

PMID- 19098007
TI  - Crystal structures of the GCaMP calcium sensor reveal the mechanism of
      fluorescence signal change and aid rational design.
AB  - The genetically encoded calcium indicator GCaMP2 shows promise for neural network
      activity imaging, but is currently limited by low signal-to-noise ratio. We
      describe x-ray crystal structures as well as solution biophysical and
      spectroscopic characterization of GCaMP2 in the calcium-free dark state, and in
      two calcium-bound bright states: a monomeric form that dominates at intracellular
      concentrations observed during imaging experiments and an unexpected domain
      swapped dimer with decreased fluorescence. This series of structures provides
      insight into the mechanism of Ca2+-induced fluorescence change. Upon calcium
      binding, the calmodulin (CaM) domain wraps around the M13 peptide, creating a new
      domain interface between CaM and the circularly permuted enhanced green
      fluorescent protein domain. Residues from CaM alter the chemical environment of
      the circularly permuted enhanced green fluorescent protein chromophore and,
      together with flexible inter-domain linkers, block solvent access to the
      chromophore. Guided by the crystal structures, we engineered a series of GCaMP2
      point mutants to probe the mechanism of GCaMP2 function and characterized one
      mutant with significantly improved signal-to-noise. The mutation is located at a
      domain interface and its effect on sensor function could not have been predicted
      in the absence of structural data.

PMID- 19098009
TI  - Interaction between Arabidopsis Ca2+/H+ exchangers CAX1 and CAX3.
AB  - In plants, high capacity tonoplast cation/H(+) antiport is mediated in part by a
      family of CAX (cation exchanger) transporters. Functional association between
      CAX1 and CAX3 has previously been inferred; however, the nature of this
      interaction has not been established. Here we analyze the formation of "hetero
      CAX" complexes and their transport properties. Co-expressing both CAX1 and CAX3
      mediated lithium and salt tolerance in yeast, and these phenotypes could not be
      recapitulated by expression of deregulated versions of either transporter.
      Coincident expression of Arabidopsis CAX1 and CAX3 occurs during particular
      stress responses, flowering, and seedling growth. Analysis of cax1, cax3, and
      cax1/3 seedlings demonstrated similar stress sensitivities. When plants expressed
      high levels of both CAXs, alterations in transport properties were evident that
      could not be recapitulated by high level expression of either transporter
      individually. In planta coimmunoprecipitation suggested that a protein-protein
      interaction occurred between CAX1 and CAX3. In vivo interaction between the CAX
      proteins was shown using a split ubiquitin yeast two-hybrid system and gel shift
      assays. These findings demonstrate cation exchange plasticity through hetero-CAX
      interactions.

PMID- 19098010
TI  - The association between ankle brachial pressure index and pulse wave velocity:
      clinical implication of pulse wave velocity.
AB  - OBJECTIVE: The aim of this study was to assess the relationship between ankle
      brachial pressure index and pulse wave velocity in patients with peripheral
      arterial disease. METHODS: Brachial-knee and brachial-ankle pulse wave velocity
      were measured by pneumoplethysmography using cuffs in a standard technique.
      Correlation between pulse wave velocity and Doppler-ankle brachial pressure index
      was assessed by Spearman correlation and receiver operating curves. RESULTS: A
      total of 133 claudicants were assessed. Analysis by developing receiver operating
      curves for ankle brachial pressure index and pulse wave velocity showed that
      patients with ankle brachial pressure index over 0.6 were more likely to have a
      bk-pulse wave velocity over 9.2 m/s and ba-pulse wave velocity over 9.5 m/s.
      CONCLUSION: These results show for the first time that nondiabetic vascular
      patients may have measurable significant arterial stiffness independent of an
      impaired ankle brachial pressure index. These data suggest that pulse wave
      velocity may be valuable in screening and evaluating the severity of peripheral
      arterial disease.

PMID- 19098012
TI  - Clinical outcome in patients with peripheral artery disease and renal artery
      stenosis.
AB  - BACKGROUND: There is controversy on the influence of renal artery stenosis on
      outcome in patients with peripheral artery disease. PATIENTS AND METHODS: The 12
      month impact of renal artery stenosis on declining renal function, control of
      hypertension, and incidence of major cardiovascular events in 100 consecutive
      patients undergoing angiography for peripheral artery disease was evaluated.
      RESULTS: A total of 60 patients had renal artery stenosis: 32 mild, 16 moderate,
      and 12 severe stenosis. There were no significant differences in either the
      decline of renal function (2.7 +/- 18% vs 0.9 +/- 16%), control of hypertension
      (139 +/- 16 vs 139 +/- 22 mm Hg) or number of antihypertensive drugs (1.8 +/- 1.0
      vs 1.6 +/- 0.8). Patients with renal artery stenosis had an increased incidence
      of major cardiovascular events (odds ratio: 2.3; 95% confidence interval: 1.03
      5.4), but on multivariate analysis its influence disappeared. CONCLUSIONS:
      Patients with peripheral artery disease having renal artery stenosis had similar
      decline of renal function and control of hypertension. They had an increased
      incidence of major cardiovascular events, but it may be explained by the
      confounding effect of additional variables.

PMID- 19098013
TI  - Prevalence and impact of diabetes mellitus in patients with acute myocardial
      infarction: a 10-year experience.
AB  - BACKGROUND: Diabetes mellitus is associated with a higher incidence of acute
      myocardial infarction. OBJECTIVE: To study the prevalence and outcome of patients
      with diabetes among patients with acute myocardial infarction. METHODS:
      Retrospectively, patients who presented with acute myocardial infarction in a 10
      year period were identified from the coronary care unit database. RESULTS: A
      total of 1598 Qatari patients were admitted with acute myocardial infarction, 863
      (54%) of them had diabetes mellitus (females 68.5% vs males 48.3%; P < .001). In
      hospital mortality rate was non-significantly higher in diabetic patients (18% vs
      15% P = .15). Aspirin (odds ratio 2.39, 95% confidence interval 1.96-2.90, P =
      .003] and beta-blocker use (odds ratio 1.75, 95% CI 1.21-2.52, P = .0001) were
      independently associated with reduced mortality risk. CONCLUSIONS: The prevalence
      of diabetes mellitus among patients with acute myocardial infarction in a
      geographically defined population in the developing world is high with a trend
      for poor outcomes. However, mortality was not significantly higher in diabetes
      mellitus than non-diabetes mellitus patients.

PMID- 19098014
TI  - Prostate melanosis associated with acinar adenocarcinoma.
AB  - Prostate melanosis is an uncommon lesion of uncertain etiology where melanin
      deposition is seen in the epithelium, in the stroma, or in the form of a blue
      nevus. There are three reports in the literature of melanosis seen in association
      with prostatic adenocarcinoma. This is the fourth report of this association.

PMID- 19098015
TI  - Pulmonary carcinoid tumor masquerading as a synovial sarcoma.
AB  - A rare case of pulmonary carcinoid tumor exhibiting morphologically as a
      monophasic synovial sarcoma is reported. The patient is a 37-year-old man who
      presented with shortness of breath for several weeks. The chest computed
      tomographic scan showed a 3.5 cm pulmonary mass in the left lower lobe.The lesion
      was an oval, tan nodule displaying features of monophasic synovial sarcoma.
      Immunohistochemical studies were performed and included a carcinoid tumor as a
      main differential diagnosis. Reverse transcriptase polymerase chain reaction and
      fluorescence in situ hybridization studies were negative for a molecular evidence
      of synovial sarcoma. This case further emphasizes the capacity of pulmonary
      carcinoid tumor cells to show various morphologic expressions even toward a
      mesenchymal differentiation mimicking a synovial sarcoma.

PMID- 19098016
TI  - Dedifferentiated chromophobe renal cell carcinoma with massive osteosarcoma-like
      divergent differentiation: a singular entity in the spectrum of retroperitoneal
      calcifying tumors.
AB  - Sarcomatoid change in renal cell carcinoma is the result of the dedifferentiation
      of the "parent" tumor into a high-grade malignancy characterized by sarcoma-like
      features and associated with an accelerated clinical course and poorer prognosis.
      Any of the renal cell carcinoma subtypes can undergo sarcomatoid
      dedifferentiation, with the chromophobe variant being the most prone. The present
      report describes the case of a woman affected by a classic chromophobe renal cell
      carcinoma that developed dedifferentiation accompanied by a very rare
      osteosarcoma-like divergent differentiation, which constituted about 90% of the
      entire retroperitoneal mass. In addition to presenting the relevant imaging,
      histopathological, and immunohistochemical findings, this article briefly
      discusses the main differential diagnosis of retroperitoneal ossifying/
      calcifying masses, which could give rise to diagnostic problems either in small
      biopsies or at imaging.

PMID- 19098017
TI  - Juxtaglomerular cell tumor of the kidney: case report and differential diagnosis
      with emphasis on pathologic and cytopathologic features.
AB  - This study presents a case of juxtaglomerular cell tumor (JCT) in a 12-year-old
      girl with hypertension. Fine needle aspirate (FNA) cytology demonstrated a
      neoplasm with features of a papillary carcinoma, prompting a right radical
      nephrectomy. Histological examination revealed solid sheets of round epithelioid
      cells with eosinophilic granular cytoplasm, and distinct cell borders in a
      background of widespread hemorrhage. Electron microscopy revealed cytoplasmic
      renin granules. The differential diagnosis of a renal mass in a young patient
      with hypertension includes JCT, Wilm's tumor, and renal cell carcinoma, which may
      produce renin. The renin granules detected by electron microscopy are
      characteristic of JCT, and the diagnosis is confirmed by ultrastructural study.
      FNA cytology is not sensitive enough for the diagnosis of JCT and its results
      must be carefully interpreted.

PMID- 19098018
TI  - Complement factor H Y402H decreases cardiovascular disease risk in patients with
      familial hypercholesterolaemia.
AB  - AIMS: Activation of the complement system seems an important link between
      inflammation and atherogenesis. The Y402H polymorphism of complement factor H
      (CFH) has been associated with cardiovascular events, but results are conflicting
      and possibly modified by age of onset of cardiovascular disease (CVD). METHODS
      AND RESULTS: We determined whether or not the Y402H polymorphism influenced CVD
      risk in a multicentre cohort study involving 2,016 unrelated patients with
      familial hypercholesterolaemia (FH), who have an extremely increased
      susceptibility to premature CVD. We identified 261 individuals who were
      homozygous for the polymorphism (CC genotype; 12.9%), 929 individuals who were
      heterozygous (TC genotype; 46.1%), and 826 individuals carried the wild-type (TT
      genotype; 41.0%). During 95 115 person years, 644 patients had a cardiovascular
      event. Carriers of the CC genotype had a decreased risk of CVD (hazard ratio
      0.67, 95% confidence interval 0.51-0.87; P = 0.003) relative to the other
      genotype groups. This association was unaltered after adjustment for clinically
      relevant cardiovascular risk factors or age effects. CONCLUSION: Among patients
      with severely increased risk of early onset CVD, the Y402H CFH variant was
      inversely associated with susceptibility to CVD. This suggests that CFH is a
      modifier gene of CVD.

PMID- 19098019
TI  - Incidence, determinants, and prognostic value of reverse left ventricular
      remodelling after primary percutaneous coronary intervention: results of the
      Acute Myocardial Infarction Contrast Imaging (AMICI) multicenter study.
AB  - AIMS: Few data are available on the extent and prognostic value of reverse left
      ventricular remodelling (r-LVR) after ST-elevation acute myocardial infarction
      (STEMI). We sought to evaluate incidence, major determinants, and long-term
      clinical significance of r-LVR in a group of STEMI patients treated with primary
      percutaneous coronary intervention (PPCI). In particular, the role of preserved
      microvascular flow within the infarct zone in inducing r-LVR has been
      investigated. METHODS AND RESULTS: Serial echocardiograms (2DE) and myocardial
      contrast study were obtained within 24 h of coronary recanalization (T1) and at
      pre-discharge (T2) in 110 reperfused STEMI patients. Follow-up 2DE was scheduled
      after 6 months (T3). Two-year clinical follow-up was obtained. Reverse
      remodelling was defined as a reduction >10% in LV end-systolic volume (LVESV) at
      6 months follow-up. r-LVR occurred in 39% of study population. At multivariable
      analysis, independent predictors of r-LVR were an effective microvascular reflow
      within the infarct zone, the in-hospital improvement of myocardial perfusion, an
      initial large LVESV, and a short time to reperfusion. Cox analysis identified r
      LVR as the only independent predictor of 2-year event-free survival. Combined
      events rate was significantly higher among patients without compared to those
      with r-LVR (log-rank test P < 0.05). CONCLUSION: r-LVR frequently occurs in STEMI
      patients treated with PPCI and it is an important predictor of favourable long
      term outcome. A preserved microvascular perfusion within the infarct zone is the
      major determinant of r-LVR.

PMID- 19098020
TI  - Regional myocardial perfusion reserve determined using myocardial perfusion
      magnetic resonance imaging showed a direct correlation with coronary flow
      velocity reserve by Doppler flow wire.
AB  - AIMS: Quantitative analysis of rest-stress myocardial perfusion magnetic
      resonance imaging (MRI) can provide assessments of regional myocardial perfusion
      reserve (MPR). The purpose of this study was to compare regional MPR determined
      by myocardial perfusion MRI with coronary flow reserve (CFR) by intracoronary
      Doppler flow wire. METHODS AND RESULTS: Twenty patients with suspected coronary
      artery disease (CAD) were studied. Average peak velocity was measured by Doppler
      flow wire in the resting state and during adenosine triphosphate (ATP) stress in
      36 coronary arteries. CFR measurements for each patient were performed in the
      culprit and one non-culprit non-stenotic artery. First-pass, contrast-enhanced
      myocardial perfusion MR images were obtained in the resting state and during ATP
      stress within the week before the Doppler wire procedure. Regional myocardial
      blood flow (MBF) was quantified in 16 myocardial segments by analysing arterial
      input and myocardial output using a Patlak plot method. MPR was calculated as
      stress MBF divided by rest MBF. CFR measured by Doppler flow wire was compared
      with MPR in the myocardial segments corresponding to vessel territories. The
      average MPR measured by perfusion MRI was 1.77 +/- 0.62 for the culprit arteries
      and 3.45 +/- 0.78 for the non-culprit arteries, respectively (P < 0.001). The
      averaged CFR by Doppler flow wire was 1.72 +/- 0.44 in the culprit arteries and
      3.14 +/- 0.74 in the non-culprit arteries, respectively (P < 0.001). For both
      culprit and non-culprit vessel groups, significant direct correlations were
      observed between MR assessments of MPR and Doppler assessments of CFR (culprit
      artery: R = 0.87, Non-culprit artery: R = 0.86) On Bland-Altman analysis, the
      mean differences between MPR determined by myocardial perfusion MRI and CFR
      measured by Doppler wire were 0.05 in culprit arteries (95% limit of agreement; 
      0.65 to 0.56) and 0.36 in non-culprit arteries (95% limit of agreement; -1.24 to
      0.44). The sensitivity and specificity of MR measurement of MPR for predicting
      physiologically significant reduction of Doppler CFR (<2) was 88% (95% CI 61.7
      98.5) and 90% (95% CI 68.3-98.8), respectively. CONCLUSION: The current results
      using Doppler flow wire as a reference method demonstrated that quantitative
      analysis of stress-rest myocardial perfusion MRI can provide a non-invasive
      assessment of reduced MPR in patients with CAD.

PMID- 19098025
TI  - Epigenetics in multiple sclerosis susceptibility: difference in transgenerational
      risk localizes to the major histocompatibility complex.
AB  - Multiple sclerosis (MS) susceptibility demonstrates a complex pattern of
      inheritance. Haplotypes containing HLA-DRB1*1501 carry most of the genetic risk.
      Epidemiological evidence implicating epigenetic factors includes complex
      distortion of disease transmission seen in aunt/uncle-niece/nephew (AUNN) pairs.
      Unexpectedly, in AUNN families we found that allele frequencies for HLA-DRB1*1501
      were different between the first and second generations affected. Affected aunts
      had significantly lower HLA-DRB1*15 frequency compared with their affected nieces
      (chi(2) = 9.90, P = 0.0016), whereas HLA-DRB1*15 frequency in affected males
      remains unaltered across the two generations (chi(2) = 0.23, P = 0.63). We
      compared transmissions for the HLA-DRB1*15 allele using a family-based
      transmission disequilibrium test approach in 1690 individuals from 350 affected
      sibling pair (ASP) families and 960 individuals from 187 AUNN families.
      Transmissions differed between the ASP and the AUNN families (chi(2) = 6.92; P =
      0.0085). The risk carried by HLA-DRB1*15 was increased in families with affected
      second-degree relatives (AUNN: OR = 4.07) when compared with those consisting
      only first-degree relatives (ASP: OR = 2.17), establishing heterogeneity of risk
      among HLA-DRB1*15 haplotypes based on whether collateral parental relatives are
      affected. These observations strongly implicate gene-environment interactions in
      susceptibility and more specifically, that epigenetic modifications differentiate
      among human leukocyte antigen class II risk haplotypes and are involved in the
      determination of the gender bias in MS. These data strongly suggest that the
      female-specific increasing risk of MS is mediated through these alleles or
      adjacent variation. The comparison of transmission of the same allele in
      vertically affected pedigrees (AUNN) to collinear sibling pairs (ASP) may provide
      a useful screen for putative epigenetic marks.

PMID- 19098026
TI  - Matching methods for observational microarray studies.
AB  - MOTIVATION: We address the problem of identifying differentially expressed genes
      between two conditions in the scenario where the data arise from an observational
      study, in which confounding factors are likely to be present. RESULTS: We suggest
      to use matching methods to balance two groups of observed cases on measured
      covariates, and to identify differentially expressed genes using a test suited to
      matched data. We illustrate this approach on two microarray studies: the first
      study consists of data from patients with two cancer subtypes, and the second
      study consists of data from AMKL patients with and without Down syndrome.
      AVAILABILITY: R code (www.r-project.org) for implementing our approach is
      included as Supplementary Material. SUPPLEMENTARY INFORMATION: Supplementary data
      are available at Bioinformatics online.

PMID- 19098027
TI  - SNPnexus: a web database for functional annotation of newly discovered and public
      domain single nucleotide polymorphisms.
AB  - MOTIVATION: Design a new computational tool allowing scientists to functionally
      annotate newly discovered and public domain single nucleotide polymorphisms in
      order to help in prioritizing targets in further disease studies and large-scale
      genotyping projects. SUMMARY: SNPnexus database provides functional annotation
      for both novel and public SNPs. Possible effects on the transcriptome and
      proteome levels are characterized and reported from five major annotation systems
      providing the most extensive information on alternative splicing. Additional
      information on HapMap genotype and allele frequency, overlaps with potential
      regulatory elements or structural variations as well as related genetic diseases
      can be also retrieved. The SNPnexus database has a user-friendly web interface,
      providing single or batch query options using SNP identifiers from dbSNP as well
      as genomic location on clones, contigs or chromosomes. Therefore, SNPnexus is the
      only database currently providing a complete set of functional annotations of
      SNPs in public databases and newly detected from sequencing projects. Hence, we
      describe SNPnexus, provide details of the query options, the annotation
      categories as well as biological examples of use. AVAILABILITY: The SNPnexus
      database is freely available at http://www.snp-nexus.org.

PMID- 19098028
TI  - PuMA: Bayesian analysis of partitioned (and unpartitioned) model adequacy.
AB  - SUMMARY: The accuracy of Bayesian phylogenetic inference using molecular data
      depends on the use of proper models of sequence evolution. Although choosing the
      best model available from a pool of alternatives has become standard practice in
      statistical phylogenetics, assessment of the chosen model's adequacy is rare.
      Programs for Bayesian phylogenetic inference have recently begun to implement
      models of sequence evolution that account for heterogeneity across sites beyond
      variation in rates of evolution, yet no program exists to assess the adequacy of
      these models. PuMA implements a posterior predictive simulation approach to
      assessing the adequacy of partitioned, unpartitioned and mixture models of DNA
      sequence evolution in a Bayesian context. Assessment of model adequacy allows
      empirical phylogeneticists to have appropriate confidence in their results and
      guides efforts to improve models of sequence evolution. AVAILABILITY: This
      program is available as source code, a Java.jar application, and a native Mac OS
      X application. It is distributed under the terms of the GNU General Public
      License at http://code.google.com/p/phylo-puma.

PMID- 19098029
TI  - SNPHarvester: a filtering-based approach for detecting epistatic interactions in
      genome-wide association studies.
AB  - MOTIVATION: Hundreds of thousands of single nucleotide polymorphisms (SNPs) are
      available for genome-wide association (GWA) studies nowadays. The epistatic
      interactions of SNPs are believed to be very important in determining individual
      susceptibility to complex diseases. However, existing methods for SNP interaction
      discovery either suffer from high computation complexity or perform poorly when
      marginal effects of disease loci are weak or absent. Hence, it is desirable to
      develop an effective method to search epistatic interactions in genome-wide
      scale. RESULTS: We propose a new method SNPHarvester to detect SNP-SNP
      interactions in GWA studies. SNPHarvester creates multiple paths in which the
      visited SNP groups tend to be statistically associated with diseases, and then
      harvests those significant SNP groups which pass the statistical tests. It
      greatly reduces the number of SNPs. Consequently, existing tools can be directly
      used to detect epistatic interactions. By using a wide range of simulated data
      and a real genome-wide data, we demonstrate that SNPHarvester outperforms its
      recent competitor significantly and is promising for practical disease prognosis.
      AVAILABILITY: http://bioinformatics.ust.hk/SNPHarvester.html.

PMID- 19098030
TI  - SAFEGUI: resampling-based tests of categorical significance in gene expression
      data made easy.
AB  - SUMMARY: A large number of websites and applications perform significance testing
      for gene categories/pathways in microarray data. Many of these packages fail to
      account for expression correlation between transcripts, with a resultant
      inflation in Type I error. Array permutation and other resampling-based
      approaches have been proposed as solutions to this problem. SAFEGUI provides a
      user-friendly graphical interface for the assessment of categorical significance
      in microarray studies, while properly accounting for the effects of correlations
      among genes. SAFEGUI incorporates both permutation and more recently proposed
      bootstrap algorithms that are demonstrated to be more powerful in detecting
      differential expression across categories of genes. AVAILABILITY:
      http://cebc.unc.edu/software/.

PMID- 19098031
TI  - The vascular theory of migraine--a great story wrecked by the facts.

PMID- 19098032
TI  - Retrobulbar haemodynamics and carotid wall thickness in patients with non
      arteritic anterior ischaemic optic neuropathy.
AB  - AIM: To compare retrobulbar haemodynamics and ipsilateral carotid wall thickness
      of patients with unilateral non-arteritic anterior ischaemic optic neuropathy
      (NAION) with their contralateral side. METHODS: Seventeen patients with
      unilateral NAION participated in this study. By means of Colour Doppler imaging,
      the blood-flow velocities of the ophthalmic artery were measured. Intima-media
      thickness (IMT) of common carotid and internal carotid arteries were measured
      using B-mode ultrasonography. Measurements of the affected side were compared
      with the non-involved side. RESULTS: Flow velocities in the ophthalmic arteries
      on the side of the eyes with NAION were significantly decreased compared with
      those on the side of the unaffected eyes (p<0.001). In addition, in all patients,
      both common and internal carotid artery IMT were significantly greater on the
      side of the NAION compared with the contralateral side (p<0.001). CONCLUSION:
      NAION may be associated with decreased retrobulbar flow velocities and increased
      carotid wall thickness.

PMID- 19098034
TI  - Trachoma: global magnitude of a preventable cause of blindness.
AB  - OBJECTIVES: Trachoma is the leading cause of infectious blindness worldwide. It
      is known to be highly correlated with poverty, limited access to healthcare
      services and water. In 2003, the WHO estimated that 84 million people were
      suffering from active trachoma, and 7.6 million were severely visually impaired
      or blind as a result of trachoma: this study provides an updated estimate of the
      global prevalence of trachoma based on the most recent information available.
      METHODS: A literature search of recent published and unpublished surveys in the
      57 endemic countries was carried out: the result of surveys that used the WHO
      trachoma grading system and additional information from regional and country
      experts served as a basis to determine the prevalence of trachoma in each
      country. RESULTS: Population-based surveys provided recent information for 42 out
      of 57 endemic countries. 40.6 million people are estimated to be suffering from
      active trachoma, and 8.2 million are estimated to have trichiasis. CONCLUSIONS:
      The current estimate of prevalence of trachoma is lower than the previous WHO
      estimates: this can be explained by the success in implementing control strategy,
      by more accurate data, as well as by socio-economic development in endemic
      countries.

PMID- 19098033
TI  - Late-onset retinal macular degeneration: clinical insights into an inherited
      retinal degeneration.
AB  - AIM: This study describes, in detail, the phenotype of late-onset retinal macular
      degeneration (L-ORMD) an inherited condition affecting both the retina and
      anterior segment. A staging based on clinical characteristics is proposed, and
      the relevance of this condition to current understanding of age-related macular
      degeneration is discussed. METHODS: A systematic review of the literature
      regarding this condition supports a detailed description of the natural history.
      Clinical experiences in identifying, monitoring and managing patients are also
      presented. RESULTS: L-ORMD is a rare fully penetrant autosomal dominant condition
      resulting from a mutation in the C1QTNF5 gene on chromosome 11. Affected
      individuals develop bilateral loss of vision, dark-adaptation abnormalities,
      fundus drusen-like yellow spots, midperipheral pigmentation, choroidal
      neovascularisation, chorioretinal atrophy and long anteriorly inserted lens
      zonules. Patients may benefit from treatment with high-dose vitamin A.
      CONCLUSIONS: Raised awareness of L-ORMD should lead to earlier diagnosis and
      improved care for patients. New antivascular endothelial growth factor treatment
      may provide a new possibility for management. A deeper insight into molecular and
      genetic mechanisms of L-ORMD may suggest avenues to explore new treatments of
      this disorder.

PMID- 19098035
TI  - Provision and cost of children's and young people's eye services in the UK:
      findings from a single primary care trust.
AB  - AIMS/BACKGROUND: Population-based information is useful for future strategic
      planning of healthcare resources. We wished to describe and cost the provision of
      eye services, beyond those of basic primary and emergency care, for the
      paediatric population of a single primary care trust. METHODS: Data from
      healthcare purchaser and provider records were collected for the year 2004/5 on
      provision and costing of hospital eye services, provision of spectacle vouchers,
      orthoptic screening, social services and visual-impairment team services to
      children in the Huntingdonshire Primary Care Trust population. RESULTS: In the
      year of study, in a population of 33,564 aged under 18 years, 1870 (5.6%)
      children underwent screening by an orthoptist. 1970 (5.9%) children required
      outpatient appointments, 445 (1.3%) were prescribed spectacles, and 87 (0.3%)
      children needed surgical procedures. A small proportion (69, 0.2%) of children
      were visually impaired. The total cost of providing comprehensive eye services to
      children within Hunts PCT was pound 366,727. CONCLUSION: Although the prevalence
      of significant visual impairment is low in childhood, overall, eye conditions are
      common in children and may have lifelong implications. The resources required to
      provide a comprehensive paediatric eye service, to screen for and manage common
      eye conditions, and support those with serious eye conditions or visual
      impairment, are significant. This study aids quantified prediction of future
      service usage, and facilitates decision-making on resource allocation and
      workforce organisation for children's eye care in the UK.

PMID- 19098036
TI  - Paediatric retinal detachment: comparison of high myopia and extreme myopia.
AB  - AIMS: To compare the clinical features and surgical outcomes of paediatric
      retinal detachment (RD) in high myopia and extreme myopia. METHODS: The clinical
      charts of 107 children who experienced RD and had a spherical equivalent (SE) of
      at least 6.00 dioptres (D) were reviewed. The patients were separated into a high
      myopia group (SE -6.0 to -10.0 D) and extreme myopia group (SE >-10.0 D). RD
      characteristics and outcomes were compared between these two groups. RESULTS:
      There were significant differences between the two groups in total RD (p<0.001),
      the presence of posterior staphyloma (p<0.001) and some types of breaks. More
      eyes in the extreme myopia group required vitrectomy after the initial RD repair.
      In the high myopia group, retinal reattachment was achieved in 79 eyes (97.5%) at
      the end of the intervention, whereas in the extreme myopia group, retinal
      reattachment was achieved in 22 eyes (73.3%). Multiple logistic regression showed
      that a higher refractive error was the only negative predictor of surgical
      outcome (p = 0.026). CONCLUSION: Due to differences in aetiologies, clinical
      characteristics, required surgical procedure after initial repair, surgical and
      functional outcomes, paediatric RD with extreme myopia should be addressed
      differently from paediatric RD with high myopia.

PMID- 19098037
TI  - The association between retinal vein ophthalmodynamometric force change and optic
      disc excavation.
AB  - AIM: Retinal vein ophthalmodynamometric force (ODF) is predictive of future optic
      disc excavation in glaucoma, but it is not known if variation in ODF affects
      prognosis. We aimed to assess whether a change in ODF provides additional
      prognostic information. METHODS: 135 eyes of 75 patients with glaucoma or being
      glaucoma suspects had intraocular pressure (IOP), visual fields, stereo optic
      disc photography and ODF measured on an initial visit and a subsequent visit at
      mean 82 (SD 7.3) months later. Corneal thickness and blood pressure were recorded
      on the latter visit. When venous pulsation was spontaneous, the ODF was recorded
      as 0 g. Change in ODF was calculated. Flicker stereochronoscopy was used to
      determine the occurrence of optic disc excavation, which was modelled against the
      measured variables using multiple mixed effects logistic regression. RESULTS:
      Change in ODF (p = 0.046) was associated with increased excavation. Average IOP
      (p = 0.66) and other variables were not associated. Odds ratio for increased
      optic disc excavation of 1.045 per gram ODF change (95% CI 1.001 to 1.090) was
      calculated. CONCLUSION: Change in retinal vein ODF may provide additional
      information to assist with glaucoma prognostication and implies a significant
      relationship between venous change and glaucoma patho-physiology.

PMID- 19098039
TI  - Are we doing too many cataract operations? Cataract surgery: a global
      perspective.

PMID- 19098040
TI  - Nosocomial adenovirus keratoconjunctivitis.

PMID- 19098041
TI  - Giant retinal pigment epithelial tear after laser photocoagulation for diabetic
      retinopathy.

PMID- 19098043
TI  - "Wool over eyes": Holmgren's Skeins and Thomson's Stick.

PMID- 19098042
TI  - Is there overutilisation of cataract surgery in England?
AB  - OBJECTIVES: Following a 3.7-fold increase in the rate of cataract surgery in the
      UK between 1989 and 2004, concern has been raised as to whether this has been
      accompanied by an excessive decline in the threshold such that some operations
      are inappropriate. The objective was to measure the impact of surgery on a
      representative sample of patients so as to determine whether or not
      overutilisation of surgery is occurring. DESIGN: Prospective cohort assessed
      before and 3 months after surgery. SETTING: Ten providers (four NHS hospitals,
      three NHS treatment centres, three independent sector treatment centres) from
      across England. PARTICIPANTS: 861 patients undergoing first eye (569) or second
      eye (292) cataract surgery provided preoperative data of whom 745 (87%) completed
      postoperative questionnaires. MAIN OUTCOME MEASURES: Patient-reported visual
      function (VF-14); general health status and quality of life (EQ5D); postoperative
      complications; overall view of the operation and its impact. RESULTS: Overall,
      visual function improved (mean VF-14 score increased from 83.2 (SD 17.3) to 93.7
      (SD 13.2)). Self-reported general health status deteriorated (20.3% fair or poor
      before surgery compared with 25% afterwards) which was reflected in the mean EQ5D
      score (0.82 vs 0.79; p = 0.003). At least one complication was reported by 66
      (8.9%) patients, though this probably overestimated the true incidence. If the
      appropriateness of surgery is based on an increase in VF-14 score of 5.5 (that
      corresponds to patients' reporting being "a little better"), 30% of operations
      would be deemed inappropriate. If an increase of 12.2 (patients' reports of being
      "much better") is adopted, the proportion inappropriate is 49%. Using a different
      approach to determining a minimally important difference, the proportion
      inappropriate would be closer to 20%. Although visual function (VF-14) scores
      were unchanged or deteriorated in 25% of patients, 93.1% rated the results of the
      operation as "good," "very good" or "excellent," and 93.5% felt their eye problem
      was "better." This partly reflects inadequacies in the validity of the VF-14.
      CONCLUSIONS: Improvement in the provision of cataract surgery has been
      accompanied by a reduction in the visual function threshold. However,
      methodological difficulties in measuring the impact of cataract surgery on visual
      function and quality of life mean it is impossible to determine whether or not
      overutilisation of cataract surgery is occurring.

PMID- 19098044
TI  - Central retinopathy associated with ciliary body and choroidal melanomas.

PMID- 19098045
TI  - Type I Boston keratoprosthesis with cataract extraction and intraocular lens
      placement for visual rehabilitation of herpes zoster ophthalmicus: the "KPro
      Triple".
AB  - INTRODUCTION: Management of corneal scarring following herpes zoster ophthalmicus
      (HZO) is challenging due to the dense corneal anesthesia that results from viral
      damage to the subepithelial nerve plexus. These patients have significant risk of
      graft failure following traditional corneal transplantation. We present a case of
      a 74-year-old white woman with counting fingers vision from HZO-associated
      corneal scarring and mature cataract where visual rehabilitation was accomplished
      with a Type I Boston keratoprosthesis (KPro) and concurrent extracapsular
      cataract extraction and posterior chamber intraocular lens placement (the "KPro
      Triple"). One month following surgery, the patient's uncorrected visual acuity
      improved to 20/25; this level of vision has been maintained for 7 months at
      present. SURGICAL TECHNIQUE (SEE VIDEO): The keratoprosthesis is assembled by
      creating a sandwich composed of the KPro front plate, the donor cornea, and the
      KPro backplate that is secured with a locking ring. The host cornea is then
      trephined and posterior synechiae lysed to allow access to the mature cataract.
      The cataract is manually expressed and a posterior chamber intraocular lens
      implanted. The assembled keratoprosthesis is then sutured into position with 9.0
      nylon. A bandage contact lens is placed. COMMENT: In patients with severe
      neurotrophic keratopathy, traditional penetrating keratoplasty is fraught with
      problems, including poor epithelial healing and corneal ulceration. The Boston
      KPro can provide rapid visual rehabilitation, despite corneal anaesthesia in
      these patients, and is currently our treatment of choice as a primary procedure
      for HZO patients who need corneal transplantation.

PMID- 19098046
TI  - Interference microscopy delineates cellular proliferations on flat mounted
      internal limiting membrane specimens.
AB  - AIM: To demonstrate that interference microscopy of flat mounted internal
      limiting membrane specimens clearly delineates cellular proliferations at the
      vitreomacular interface. METHODS: ILM specimens harvested during vitrectomy were
      fixed in glutaraldehyde 0.05% and paraformaldehyde 2% for 24 h (pH 7.4). In
      addition to interference microscopy, immunocytochemistry using antibodies against
      glial fibrillar acidic protein (GFAP) and neurofilament (NF) was performed. After
      washing in phosphate-buffered saline 0.1 M, the specimens were flat-mounted on
      glass slides without sectioning, embedding or any other technique of conventional
      light microscopy. A cover slide and 4',6-diamidino-2-phenylindole (DAPI) medium
      were added to stain the cell nuclei. RESULTS: Interference microscopy clearly
      delineates cellular proliferations at the ILM. DAPI stained the cell nuclei.
      Areas of cellular proliferation can be easily distinguished from ILM areas
      without cells. Immunocytochemistry can be performed without changing the
      protocols used in conventional microscopy. CONCLUSION: Interference microscopy of
      flat mounted ILM specimens gives new insights into the distribution of cellular
      proliferations at the vitreomacular interface and allows for determination of the
      cell density at the ILM. Given that the entire ILM peeled is seen en face, the
      techniques described offer a more reliable method to investigate the
      vitreoretinal interface in terms of cellular distribution compared with
      conventional microscopy.

PMID- 19098048
TI  - The burden of ocular comorbidity in cataract patients in West Africa.

PMID- 19098049
TI  - Late irreversible corneal oedema after laser iridotomy.

PMID- 19098050
TI  - Correlation between retinal sensitivity and photoreceptor inner/outer segment
      junction in patients with retinitis pigmentosa.

PMID- 19098051
TI  - Cataracts in three children with a newly recognised neurocutaneous malformation
      phenotype with "cutis tricolor".

PMID- 19098052
TI  - Shifting of the proliferative vitreoretinopathy milieu after tamponade with heavy
      silicone oil in eyes prone to proliferative vitreoretinopathy and bleeding.

PMID- 19098053
TI  - Denervation supersensitivity to 1% phenylephrine in Horner syndrome can be
      demonstrated 10 days after the onset of symptoms.

PMID- 19098054
TI  - Analyses of aqueous humour ghrelin levels of eyes with and without glaucoma.

PMID- 19098055
TI  - Sleep apnoea in the eye clinic.

PMID- 19098058
TI  - Immediate versus deferred coronary angioplasty in non-ST-segment elevation acute
      coronary syndromes.
AB  - BACKGROUND: The field of acute coronary syndromes is characterised by an
      increasing tendency towards early invasive catheter-based diagnostics and
      therapeutics-a practice based on observational and retrospective data. OBJECTIVE:
      To compare immediate versus deferred angioplasty in patients with non-ST-segment
      elevation acute coronary syndromes (NSTE-ACS) METHODS: A randomised, prospective
      multicentre trial was performed in patients admitted with NSTE-ACS, eligible for
      percutaneous coronary intervention (PCI). Interim analysis was performed after
      enrolment of 251 patients; PCI was appropriate in 142 patients. These patients
      were randomised to immediate PCI (n = 73) or deferred PCI (24-48 h) (n = 69).
      Patients received protocol-driven glycoprotein IIb/IIIa blockers, aspirin and
      clopidogrel. The primary end point was a composite of death, non-fatal myocardial
      infarction (MI) or unplanned revascularisation, at 30 days. After hospital
      discharge outpatient follow-up was performed at 30 days and 6 months. RESULTS:
      The incidence at 30 days of the primary end point was 60% in the group receiving
      immediate PCI and 39% in the group receiving deferred PCI (relative risk (RR) =
      1.5, 95% CI 1.09 to 2.15; p = 0.004). No deaths occurred in either group. MI was
      significantly more common in the group receiving immediate PCI (60% vs 38%, RR =
      1.6, 95% CI 1.12 to 2.28, p = 0.005). Unplanned revascularisation was similar in
      both groups. The observed difference was preserved over 6-months' follow-up.
      CONCLUSIONS: Immediate PCI was associated with an increased rate of MI in
      comparison with a 24-48 h deferred strategy, despite aggressive antithrombotic
      treatment. The results suggest that PCI for high-risk patients with non
      refractory NSTE-ACS should be delayed for at least 24 h after hospital admission.
      TRIAL REGISTRATION NUMBER: ISRCTN80874637.

PMID- 19098059
TI  - Finding sex partners on the internet: what is the risk for sexually transmitted
      infections?
AB  - OBJECTIVE: To assess the association between sexual encounters with internet
      partners and current Chlamydia trachomatis (Ct) and Neisseria gonorrhoeae (GC)
      infections. METHODS: Between August 2006 and March 2008, patients at the Denver
      Metro Health Clinic were routinely asked about sexual encounters with internet
      partners. This retrospective case-control study was limited to patients who
      tested for Ct/GC at their visit. Analyses were stratified by sexual orientation
      to account for differences in baseline risk behaviours. RESULTS: Of 14 955
      patients with a valid Ct/GC test result, 2802 (19%) were infected with Ct/GC.
      Stratified by sexual orientation, the prevalence of Ct/GC infection was 17% for
      men who have sex with men (MSM), 21% for men who have sex with women (MSW) and
      16% for women. A total of 339 (23%) MSM, 192 (3%) MSW and 98 (2%) women reported
      having a sexual encounter with a person they met on the internet in the past 4
      months. The estimates of the association between recent internet sex partner and
      current Ct/GC infection were not significant for MSM (risk ratio (RR): 1.12, 95%
      confidence interval (CI): 0.84 to 1.49) and women (RR: 0.81, 95% CI 0.45 to
      1.48). However, the association appeared to be significantly protective among MSW
      (RR: 0.66, 95% CI 0.44 to 0.98). CONCLUSIONS: Sexual encounters with internet
      partners did not appear to be associated with increased risk of current Ct/GC
      infection among people seeking care at a sexual health clinic. Seeking sexual
      partners on the internet is a complex behaviour and its implications for STI/HIV
      infection are not fully understood.

PMID- 19098060
TI  - Thyrotropin-secreting pituitary tumours: significance of "atypical adenomas" in a
      series of 10 patients and association with Hashimoto thyroiditis as a cause of
      delay in diagnosis.
AB  - BACKGROUND: Thyrotropin-secreting adenomas (TSH-As) are rare and, according to
      the World Health Organization criteria (WHO 2004), a significant proportion of
      them present features of atypical adenomas at the time of diagnosis. AIMS: To
      determine the frequency of "atypical adenomas" and the significance of this
      definition as regards follow-up. To investigate their possible association with
      Hashimoto thyroiditis, leading to a delay in diagnosis. METHODS: Case notes for
      patients who underwent trans-sphenoidal surgery between 1992 and 2006 were
      retrieved. Follow-up ranged from 6 to 180 months. RESULTS: Ten cases of TSH-As
      out of 908 pituitary adenomas were selected. Before surgery, eight patients had
      hyperthyroidism, one was euthyroid and another one showed hypothyroidism
      associated with Hashimoto thyroiditis. All cases were macroadenomas; six of them
      were invasive. Three cases met the criteria for classification as atypical. In
      none of the cases, including the three "atypical adenomas", were clinical or
      radiological signs of recurrence observed. CONCLUSIONS: The three cases with
      features of atypical adenoma did not recur or metastasise, suggesting that, at
      least in the present series, a strict relationship between the morphological
      criteria for diagnosing atypical adenomas and biological behaviour may be
      sometimes lacking. Furthermore, the casual association of TSH-As with Hashimoto
      thyroiditis may led to an adjunctive delay in diagnosis, because of low thyroid
      hormone levels.

PMID- 19098061
TI  - Stromal tumours: which diagnostic approach?

PMID- 19098062
TI  - The future of the quality and outcomes framework.

PMID- 19098064
TI  - A transactional model of sleep-wake regulation in infants born preterm or low
      birthweight.
AB  - OBJECTIVE: To test a transactional model of sleep-wake development in infants
      born preterm or low birthweight (PT LBW), which may inform clinical practice,
      interventions, and future research in this at risk population. METHODS: One
      hundred and twenty-eight mother-infant dyads participated from hospital discharge
      to 4 months postterm. Assessments of prematurity, infant sleep-wake patterns,
      maternal interaction quality, depression, feeding route, and sociodemographic
      factors were conducted. RESULTS: Path analyses revealed that maternal
      interactions directly related to infant sleep patterns and family
      sociodemographic risks related to less optimal parenting. In addition, bottle fed
      infants experienced fewer night wakings and more nighttime sleep. CONCLUSIONS:
      Two potential pathways to sleep patterns in PT LBW infants were identified. The
      findings suggest directions for clinical work, such as supporting healthy infant
      sleep through parenting interventions or supporting interpersonal relations
      between parents and their PT LBW infants by encouraging more daytime naps.
      Additionally, clinicians should assess parents' nighttime sleep concerns within
      the larger sociodemographic and feeding context.

PMID- 19098065
TI  - Differences in sickness absence in Sweden and Denmark: the cross national HAKNAK
      study.
AB  - AIM: To investigate potential differences in sickness absence among public sector
      employees in Sweden and Denmark, and to what extent a difference was associated
      with age, gender, physical and psychosocial work environment exposures, lifestyle
      factors, self-rated health or work ability. METHODS: In 2000, two cross-sectional
      samples of 8562 public sector employees in Sweden and Denmark were surveyed. The
      study outcome, self-reported number of sick-leave days the year preceding
      interview, was dichotomized into 7 days or less, and more than 7 days. Chi square
      test was used to analyse distribution of dependent and independent variables in
      the two sub-cohorts. Stratified logistic regression analysis was performed to
      identify causes for absence within the two sub-cohorts, and logistic regression
      analysis was performed to study differences in sickness absence levels between
      the two sub-cohorts. RESULTS: More subjects from the Swedish study population
      reported more than 7 days of sickness absence. Factors associated with sickness
      absence were largely similar in the two countries. The difference in absence
      level between Sweden and Denmark was not associated with differences in age,
      gender, skill level, lifestyle, psychosocial or physical work environment,
      musculoskeletal symptoms or self-rated health, whereas work ability score
      decreased the difference in sickness absence level. CONCLUSION: The results could
      indicate an increased retention of employees with health problems in the Swedish
      labour market compared with the Danish labour market. A possible explanation for
      the differences in sickness absence ascertained in this study could be due to
      differences in the sickness insurance legislation.

PMID- 19098066
TI  - Sensitisation and post-transplant course after the implantation of ventricular
      assist device.
AB  - The purpose of this study was to evaluate sensitisation, occurring because of
      bridging with VAD, and development of rejection episodes after transplantation in
      selected groups of patients using triple drug immunosuppression, without
      induction or desensitisation therapy. Sensitisation using standard complement
      dependent cytotoxicity was tested in 16 patients awaiting cardiac transplantation
      before VAD placement, one month post-implantation and on a six-monthly basis
      later on. Long-term (955+/-998 days) post-transplant course of six transplanted
      post-VAD patients was compared with 19 non-bridged recipients (follow-up time
      1425+/-1273 days) of the same age. One-third of VAD recipients had developed anti
      HLA antibodies one month post-implantation; 4/16 patients were sensitised six
      months after implantation. No de novo sensitisation development was revealed in
      VAD group post-transplantation. All sensitised patients independent of VAD
      placement underwent graft rejection episodes. Only 1 of 6 VAD recipient was
      treated because of grade 2R rejection, compared to 6/19 in the non-bridged group,
      P=0.63. None of the patients had failed because of early graft rejection. In
      conclusion, VAD devices used in our centre cause low level risk for anti-HLA
      antibodies development. There were no differences in survival due to immunologic
      reasons between VAD bridged and non-bridged patients.

PMID- 19098067
TI  - Correlations between leaf toughness and phenolics among species in contrasting
      environments of Australia and New Caledonia.
AB  - BACKGROUND AND AIMS: Plants are likely to invest in multiple defences, given the
      variety of sources of biotic and abiotic damage to which they are exposed.
      However, little is known about syndromes of defence across plant species and how
      these differ in contrasting environments. Here an investigation is made into the
      association between carbon-based chemical and mechanical defences, predicting
      that species that invest heavily in mechanical defence of leaves will invest less
      in chemical defence. METHODS: A combination of published and unpublished data is
      used to test whether species with tougher leaves have lower concentrations of
      phenolics, using 125 species from four regions of Australia and the Pacific
      island of New Caledonia, in evergreen vegetation ranging from temperate shrubland
      and woodland to tropical shrubland and rainforest. Foliar toughness was measured
      as work-to-shear and specific work-to-shear (work-to-shear per unit leaf
      thickness). Phenolics were measured as 'total phenolics' and by protein
      precipitation (an estimate of tannin activity) per leaf dry mass. KEY RESULTS:
      Contrary to prediction, phenolic concentrations were not negatively correlated
      with either measure of leaf toughness when examined across all species, within
      regions or within any plant community. Instead, measures of toughness
      (particularly work-to-shear) and phenolics were often positively correlated in
      shrubland and rainforest (but not dry forest) in New Caledonia, with a similar
      trend suggested for shrubland in south-western Australia. The common feature of
      these sites was low concentrations of soil nutrients, with evidence of P
      limitation. CONCLUSIONS: Positive correlations between toughness and phenolics in
      vegetation on infertile soils suggest that additive investment in carbon-based
      mechanical and chemical defences is advantageous and cost-effective in these
      nutrient-deficient environments where carbohydrate may be in surplus.

PMID- 19098068
TI  - A proposed mechanism for physical dormancy break in seeds of Ipomoea lacunosa
      (Convolvulaceae).
AB  - BACKGROUND AND AIMS: The water-impermeable seeds of Ipomoea lacunosa undergo
      sensitivity cycling to dormancy breaking treatment, and slits are formed around
      bulges adjacent to the micropyle during dormancy break, i.e. the water gap opens.
      The primary aim of this research was to identify the mechanism of slit formation
      in seeds of this species. METHODS: Sensitive seeds were incubated at various
      combinations of relative humidity (RH) and temperature after blocking the hilar
      area in different places. Increase in seed mass was measured before and after
      incubation. Scanning electron microscopy (SEM) and staining of insensitive and
      sensitive seeds were carried out to characterize these states morphologically and
      anatomically. Water absorption was monitored at 35 and 25 degrees C at 100 % RH.
      KEY RESULTS: There was a significant relationship between incubation temperature
      and RH with percentage seed dormancy break. Sensitive seeds absorbed water
      vapour, but insensitive seeds did not. Different amounts of water were absorbed
      by seeds with different blocking treatments. There was a significant relationship
      between dormancy break and the amount of water absorbed during incubation.
      CONCLUSIONS: Water vapour seals openings that allow it to escape from seeds and
      causes pressure to develop below the bulge, thereby causing slits to form. A
      model for the mechanism of formation of slits (physical dormancy break) is
      proposed.

PMID- 19098069
TI  - Ultrasound-guided hydrosalpinx aspiration during oocyte collection improves
      outcome in IVF.

PMID- 19098070
TI  - Feasibility of ovarian cryopreservation in borderline ovarian tumours.
AB  - BACKGROUND: Borderline ovarian tumours (BOT) do not exhibit overt stromal
      invasion and are less aggressive than invasive epithelial ovarian tumours. BOT
      also arise in younger patients than those who develop epithelial ovarian tumours.
      Our aim was to evaluate the feasibility of ovarian cryopreservation (OC) in
      patients treated for BOT. METHODS: A retrospective study of data concerning young
      patients (less than 35 years of age) who underwent surgery for a BOT with OC
      planned during the surgical procedure. RESULTS: Twenty-three patients, treated
      between January 2002 and February 2008, were initially selected but six of them
      were excluded from the present study (four because the tumour was malignant and
      two because it was benign). Finally, 17 patients were diagnosed as having BOT
      based on the frozen section analysis. In nine (53%) of these cases, OC was
      finally performed. In eight cases, OC was not performed; instead, in four cases a
      simple cystectomy was finally performed (one patient was in fact pregnant at the
      time of surgery), in one case malignant disease was found and in three (18%)
      patients OC was not technically feasible because no normal ovarian parenchyma was
      evident on gross inspection. CONCLUSION: In patients treated for a BOT, OC was
      eventually feasible in 53% of patients in whom this procedure was initially
      planned. In 18%, this procedure was aborted because no macroscopic healthy
      ovarian tissue could be found.

PMID- 19098071
TI  - A genetic study of the Arabidopsis circadian clock with reference to the TIMING
      OF CAB EXPRESSION 1 (TOC1) gene.
AB  - In Arabidopsis thaliana, a consistent multiloop clock model has been widely
      adopted in many recent publications. This tentative model consists of three
      interactive feedback loops, namely the core CCA1/LHY-TOC1/X loop, the morning
      CCA1/LHY-PRR9/PRR7 loop and the evening Y-TOC1 loop, in which the undefined Y
      gene might be GI. The model in its current form provides us with a basis on which
      to address a number of fundamental issues for a better understanding of the
      molecular mechanism by which the central oscillator generates circadian rhythms.
      We have been conducting a series of genetic studies through the establishment of
      a set of combinatorial mutants. We have already characterized a prr9 prr7 double
      loss-of-function mutant that has lost the morning loop, and a cca1 lhy toc1
      triple mutant that lacks the core loop. Extension of this line of study required
      characterization of a gi toc1 double loss-of-function mutant, which is expected
      to have no evening loop, and a prr9 prr7 toc1 triple mutant, lacking both the
      morning and evening loops. Genetic analysis of both these lines is reported here.
      From the results, we have clarified the genetic linkages between GI and TOC1 and
      those between PRR9/PRR7 and TOC1 with reference to the circadian clock-associated
      phenotypes, including: (i) length of hypocotyls during early photomor-phogenesis;
      (ii) photoperiodic control of flowering time; and (iii) expression profiles of
      CCA1 and LHY under free-running conditions. These results indicate that GI is not
      sufficient to fulfill the Y role, but plays more complicated clock-associated
      roles and, interestingly, that no epistatic interaction between PRR9/PRR7 and
      TOC1 was observed. Furthermore, these clock-defective mutants could still
      generate robust, free-running rhythms at the level of transcription. Therefore,
      we speculate that an as yet undefined oscillator (or loop) continues to generate
      rhythms within the plants lacking GI/TOC1 or PRR9/PRR7/TOC1.

PMID- 19098072
TI  - Generation of hydroxyl radical in isolated pea root cell wall, and the role of
      cell wall-bound peroxidase, Mn-SOD and phenolics in their production.
AB  - The hydroxyl radical produced in the apoplast has been demonstrated to facilitate
      cell wall loosening during cell elongation. Cell wall-bound peroxidases (PODs)
      have been implicated in hydroxyl radical formation. For this mechanism, the
      apoplast or cell walls should contain the electron donors for (i) H(2)O(2)
      formation from dioxygen; and (ii) the POD-catalyzed reduction of H(2)O(2) to the
      hydroxyl radical. The aim of the work was to identify the electron donors in
      these reactions. In this report, hydroxyl radical (.OH) generation in the cell
      wall isolated from pea roots was detected in the absence of any exogenous
      reductants, suggesting that the plant cell wall possesses the capacity to
      generate .OH in situ. Distinct POD and Mn-superoxide dismutase (Mn-SOD) isoforms
      different from other cellular isoforms were shown by native gel electropho-resis
      to be preferably bound to the cell walls. Electron paramagnetic resonance (EPR)
      spectroscopy of cell wall isolates containing the spin-trapping reagent, 5
      diethoxyphosphoryl-5-methyl-1-pyrroline-N-oxide (DEPMPO), was used for detection
      of and differentiation between .OH and the superoxide radical (O(2)(-).). The
      data obtained using POD inhibitors confirmed that tightly bound cell wall PODs
      are involved in DEPMPO/OH adduct formation. A decrease in DEPMPO/OH adduct
      formation in the presence of H(2)O(2) scavengers demonstrated that this hydroxyl
      radical was derived from H(2)O(2). During the generation of .OH, the
      concentration of quinhydrone structures (as detected by EPR spectroscopy)
      increased, suggesting that the H(2)O(2) required for the formation of .OH in
      isolated cell walls is produced during the reduction of O(2) by hydroxycinnamic
      acids. Cell wall isolates in which the proteins have been denaturated (including
      the endogenous POD and SOD) did not produce .OH. Addition of exogenous H(2)O(2)
      again induced the production of .OH, and these were shown to originate from the
      Fenton reaction with tightly bound metal ions. However, the appearance of the
      DEPMPO/OOH adduct could also be observed, due to the production of O(2)(-). when
      endogenous SOD has been inactivated. Also, O(2)(-). was converted to .OH in an in
      vitro horseradish peroxidase (HRP)/H(2)O(2) system to which exogenous SOD has
      been added. Taken together with the discovery of the cell wall-bound Mn-SOD
      isoform, these results support the role of such a cell wall-bound SOD in the
      formation of .OH jointly with the cell wall-bound POD. According to the above
      findings, it seems that the hydroxycinnamic acids from the cell wall, acting as
      reductants, contribute to the formation of H(2)O(2) in the presence of O(2) in an
      autocatalytic manner, and that POD and Mn-SOD coupled together generate .OH from
      such H(2)O(2).

PMID- 19098073
TI  - Differential expression control and polarized distribution of plasma membrane
      resident SYP1 SNAREs in Arabidopsis thaliana.
AB  - Membrane trafficking to the plasma membrane (PM) is a highly organized process
      which enables plant cells to build up their bodies. SNARE (soluble N
      ethylmaleimide-sensitive factor attachment protein receptor) genes, which encode
      the proteins involved in membrane trafficking, are much more abundant in the
      Arabidopsis genome than in that of any other eukaryote. We have previously shown
      that a large number of SNARE molecules in the Arabidopsis cell are localized
      predominantly on the PM. In the present study, in order to elucidate the
      physiological function of each PM-localized SNARE, we analyzed the spatiotemporal
      expression profiling of nine SYP1s that are resident in the PM of Arabidopsis,
      and used the information thus acquired to generate transgenic Arabidopsis plants
      expressing green fluorescent protein-fused Qa-SNAREs under control of their
      authentic promoters. Among the nine SYP1s, only SYP132 is expressed ubiquitously
      in all tissues throughout plant development. The expression patterns of the other
      SYP1s, in contrast, are tissue specific, and all different from one another. A
      particularly noteworthy example is SYP123, which is predominantly expressed in
      root hair cells during root development, and shows a focal accumulation pattern
      at the tip region of root hairs. These results suggest that SYP132 is involved in
      constitutive membrane trafficking to the PM throughout plant development, while
      the other SYP1s are involved in membrane trafficking events such as root
      formation or tip growth of root hair, with some redundancy.

PMID- 19098074
TI  - Reno-prevention vs. reno-protection: a critical re-appraisal of the evidence-base
      from the large RAAS blockade trials after ONTARGET--a call for more
      circumspection.
AB  - The ACEI, captopril was introduced into clinical medicine in the early 1970s for
      hypertension. Other ACEIs and the ARBs were introduced subsequently. Following
      several RAAS blockade trials, we now have an expanded set of clinical indications
      for these agents. Despite the escalated use of these agents, we continue to
      experience an unexplained epidemic of ESRD/CKD/ARF. There are concerns regarding
      potential iatrogenic renal failure arising from these agents. A case, it would
      appear, of unintended consequences. Our publication of several reports on the
      previously unrecognized syndrome of late onset renal failure from angiotensin
      blockade (LORFFAB) in 2008 adds to this evolving literature. At the same time,
      some recent reports have questioned the veracity of claims of superior reno
      protection with these agents beyond BP lowering. A post hoc analysis of a subset
      of patients in the MICRO-HOPE cohort suggested that a previously unrecognized
      greater 24-h BP lowering achieved in the ramipril arm vs placebo could explain
      the reported benefits of the ACEI. These doubts and concerns became heightened by
      the results of the ONTARGET study. Our critical re-appraisal of the large RAAS
      blockade trials revealed design flaws and protocol contradictions that further
      these doubts and concerns. We conclude that these agents be used more
      judiciously, with better monitoring of kidney function. Treating physicians must
      consider drug discontinuation in selected patients. We also support temporary
      withdrawal of these agents before major surgical procedures, contrast media
      administration and during acute illness. Such preventative measures (reno
      prevention) would enhance the benefits of reno-protection with RAAS blockade.

PMID- 19098075
TI  - Histologically benign but clinically malignant: an unusual case of recurrent
      atrial myxoma.

PMID- 19098076
TI  - The influence of liberal alcohol consumption on glucose metabolism in patients
      with type 1 diabetes: a pilot study.
AB  - BACKGROUND: Little is known about the consequences of excessive alcohol ingestion
      in patients with type 1 diabetes. AIM: To examine the metabolic effects of acute
      ingestion of liberal amounts of alcohol in patients with type 1 diabetes. DESIGN:
      A pilot study using a randomized, placebo controlled, double blind design in
      Hospital Clinical Research Unit. METHODS: The study included 10 patients with
      type 1 diabetes (seven male, age 43.9 +/- 9.0 years, duration of diabetes 17.3 +/
      13.8 years, HbA(1c) 8.0 +/- 1.5%) who had a standard 600-calorie lunch on two
      separate occasions, together with either white wine (men eight units, women six
      units), or an equivalent volume of alcohol-free wine. Bloods were collected
      before lunch and hourly for 4 h for glucose, intermediary metabolites, counter
      regulatory hormones and inflammatory markers. RESULTS: There were no significant
      differences between alcohol and alcohol-free days in levels of glucose,
      triglycerides, free fatty acids, glycerol, cortisol and growth hormone. In
      contrast, lactate levels rose in response to the meal but with alcohol the
      overall response was augmented (P = 0.014). Beta-hydroxybutyrate levels were
      suppressed post-prandially on the alcohol-free day but were significantly
      elevated with alcohol (P < 0.001). CONCLUSION: A rise in ketones following
      alcohol ingestion occurred despite subjects being in a strictly controlled
      environment with no interruption in insulin administration. Such individuals
      might be at risk of significant ketosis in less-controlled circumstances where
      insulin administration might be more erratic. Patient education material should
      contain information to highlight these potential problems.

PMID- 19098078
TI  - Incidence of semicircular canal dehiscence in Singapore.
AB  - Semicircular canal dehiscence is a congenital syndrome that mainly affects the
      superior and, less commonly, the posterior semicircular canals. The diagnosis of
      superior semicircular canal dehiscence syndrome depends on the demonstration of a
      very small defect in the bony wall of the superior semicircular canal. Any amount
      of intact bone present excludes the diagnosis. The study will give an
      approximation of the incidence of semicircular canal dehiscence in Singapore. No
      specific data regarding the number of such cases exist currently. Retrospective
      review of CT scans of the temporal bone performed at our institution between
      January 2005 and July 2007 revealed a total of 10 such cases over this period,
      comprising 8 males and 2 females, with all cases involving the superior
      semicircular canal. Almost all of the patients scanned had evidence of previous
      or existing cholesteatoma. Three patients had bilateral superior semicircular
      canal dehiscence (all males), with an almost equal number of semicircular canal
      dehiscence on both sides for both sexes. Our study shows no significant advantage
      to obtaining reformatted oblique sagittal images for all temporal bone studies,
      unless the visualized walls show questionable defects. In these cases,
      reconstructed images are probably advantageous and should be obtained and
      reviewed.

PMID- 19098079
TI  - Imaging of patients with clinically suspected appendicitis in the Netherlands:
      conclusions of a survey.
AB  - The aim of this study was to summarize the extent of variation in imaging
      strategies in patients clinically suspected of having appendicitis. By means of a
      written survey, the policies for the imaging management of patients clinically
      suspected of having appendicitis in the Netherlands were inventoried. A
      questionnaire was sent to the departments of surgery and radiology of all 105
      Dutch hospitals, including the 8 academic medical centres, in March 2006.
      Questionnaires were returned from 98 hospitals. It was found that, in the work-up
      of patients suspected of having appendicitis, ultrasound or CT was performed in a
      minority of hospitals for 50% or more of these patients. In the majority of
      hospitals, it was carried out for less than 50% of these patients. There is a
      widespread variability in pre-operative imaging regardless of hospital type. This
      survey shows that, despite the ubiquitous presence of ultrasound and CT in Dutch
      hospitals, the pre-operative imaging work-up in patients clinically suspected of
      having acute appendicitis does not reflect this, being performed in only a
      minority of patients suspected of having acute appendicitis. Radiologists and
      surgeons alike should be aware of the positive impact of adjunctive imaging in
      this group of patients - most importantly lowering the negative appendicectomy
      rate and also lowering total hospital costs.

PMID- 19098080
TI  - Cisplatin-conjugated degradable gelatin microspheres: fundamental study in vitro.
AB  - The object of this study was to generate cisplatin-conjugated gelatin
      microspheres (GMSs) and to confirm the subsequent release of cisplatin in vitro.
      The GMSs (1 mg) were immersed in 50 microl of a cisplatin solution (0.06, 0.15,
      0.27, 0.30 or 0.54 mg ml(-1)) at 38 degrees C to allow conjugation. The cisplatin
      conjugated GMSs were then extensively washed in double-distilled water and freeze
      dried. The platinum concentration in the GMSs samples was investigated as a
      function of the concentration of cisplatin solution used in their preparation,
      the number of immersions in cisplatin (1, 2, 3, 4 or 5) and the period of
      immersion (1, 6 or 11 h). In vitro release tests were performed at different time
      intervals (1, 3, 6, 12 or 24 h) to allow the rate of cisplatin release to be
      calculated. The platinum concentration of the GMSs increased in proportion to the
      concentration of cisplatin solution and the length or number of immersions in
      cisplatin. In vitro release tests demonstrate that the release rate (%) from GMSs
      after 1, 3, 6, 12 or 24 h was 4.8, 5.5, 7.6, 10.0 and 12.4, respectively. We
      demonstrated the ability of GMSs to bind cisplatin forming cisplatin-conjugated
      GMSs. Moreover, we showed that cisplatin continued to bind GMSs strongly during
      the in vitro release test.

PMID- 19098081
TI  - Blood volume flow quantification of the brain-supplying circulation in
      fibromuscular dysplasia using 2D cine phase-contrast MRI.
AB  - To determine blood volume flow (BVF) in the brain-supplying arteries in patients
      with fibromuscular dysplasia (FMD), we used two-dimensional cine phase-contrast
      MR blood flow quantification to evaluate haemodynamic compromise. Nine patients
      with angiographically proven FMD (mean age, 46.7+/-10.4 years) of the cervical
      and intracranial arteries were examined using two-dimensional phase contrast MR
      to measure blood flow in the carotid arteries and the basilar artery (BA).
      Quantitative BVF results were compared intra- and inter-individually and also
      with the results of 15 age-matched normal controls. No patient showed evidence of
      acute or chronic infarction of the brain. FMD lesions were found in a total of 19
      arteries (internal carotid artery: n = 14; vertebral arteries: n = 5). Five
      patients demonstrated severe stenoses of cervical vessels; four patients showed
      only mild or up to moderate stenoses. Total brain BVF in all FMD patients reached
      high-normal values compared with normal controls (747+/-64 ml min(-1) vs 682+/-38
      ml min(-1)). In the five patients with severe stenotic lesions, blood flow was
      reduced in stenotic vessels and higher in the non-haemodynamically relevant
      stenosed cervical vessels. BVF was normal in the four patients with mild and
      moderate stenoses. By quantifying blood flow, we demonstrated for the first time
      changes (which can be severe) in the BVF of the brain-supplying arteries in FMD.
      Individual differences are associated with the haemodynamic relevance of the FMD
      lesions. Total BVF in patients with severe FMD was not decreased but maintained
      or even increased, possibly as an overcompensation.

PMID- 19098082
TI  - Percutaneous transluminal angioplasty of suture-mediated closure device-related
      femoral artery stenosis or occlusive disease.
AB  - This study evaluates the efficacy of percutaneous transluminal balloon
      angioplasty (PTA) to treat stenosis or occlusion following haemostasis using a
      suture-mediated closure (SMC) device. Steno-occlusion occurred in 7 (0.4%)
      patients, some with claudication, others without. Steno-occlusion was diagnosed
      immediately after haemostasis in the four patients without claudication, but
      diagnosis was delayed in all three patients with claudication. Six of the
      patients subsequently underwent PTA using a contralateral femoral arterial
      approach. Technical success, clinical response and vessel patency were evaluated
      retrospectively. Follow-up angiography revealed focal segmental steno-occlusion
      (<1 cm) in the common femoral or proximal superficial femoral artery in four
      patients and long segmental occlusion (>1 cm) in the external iliac and common
      femoral arteries in three patients. PTA was technically successful in all
      patients (6/6, 100%). Among the three patients who developed delayed onset of
      claudication, one declined treatment and the claudication improved in two.
      Doppler ultrasound obtained 28-129 days (mean; 75 days) after PTA revealed patent
      arterial flow in six patients. One patient with delayed-onset occlusion refused
      the procedure because the symptoms were mild. This study has shown that PTA is a
      useful treatment for steno-occlusion following haemostasis using the SMC device.
      Careful angiography and review of the femoral bifurcation prior to use of an SMC
      device is important.

PMID- 19098083
TI  - Safety and efficacy of a rate control protocol for cardiac CT.
AB  - The clinical application of cardiac CT is increasing, but heart rate control is
      often required to prevent motion artefact. Here, we describe a protocol for heart
      rate control in patients undergoing outpatient CT coronary angiography (CTCA).
      Among 121 consecutive patients, 75 (61.9%) with a resting heart rate >60 beats
      per minute (bpm) required rate control medication. Our protocol called for oral
      metoprolol 100 mg to be given 60 min before scanning, with patients for whom beta
      blockers were contraindicated receiving 240 mg oral verapamil. Additional 5 mg
      intravenous boluses (maximum for both drugs, 15 mg) were given if the heart rate
      remained >60 bpm prior to scanning. Of 71 patients treated with oral metoprolol,
      59 (83%) achieved a rate <or=65 bpm and 46 (65%) achieved a heart rate of <or=60
      bpm during the CTCA scan. All four patients receiving verapamil had a poor rate
      response and had heart rates >70 bpm at the time of scanning. No adverse events
      resulted from rate control medication. Image quality was closely related to heart
      rate. Severe motion artefact (Grade 3) occurred in only 0.9% of patients with a
      rate <or=60 bpm compared with 50% of patients with a rate >70 bpm. In conclusion,
      the administration of oral metoprolol according to the described protocol is a
      safe and effective way of reducing heart rate and improving scan quality in the
      majority of patients undergoing CTCA.

PMID- 19098084
TI  - Reduction of motion artefacts in non-gated dual-energy radiography.
AB  - The objective of this work was to reduce motion artefacts in non-gated dual
      energy subtraction radiography whilst preserving the contrast-to-noise ratio
      (CNR) in regions with low motion. Dual-energy radiography provides material
      selective information (soft-tissue and bone images) that may be used for improved
      detection of calcifications in lung nodules. The weighted logarithmic dual-energy
      subtraction of thoracic images performed without electrocardiogram gating results
      in motion-induced artefacts. The low-energy image was acquired at the usual dose
      setting at 60 kV. To obtain the high-energy (120 kV) information, a series of
      consecutive images at a time interval of 30 ms were made. The series integral
      dose was equivalent to the dose of a single conventional high-energy image. A
      motion-free merging technique was introduced that combines standard images
      yielding low image noise with phase-selective images yielding motion artefact
      free image regions which are used for dual-energy subtraction. Evaluations of the
      method were performed with simulations and measurements using a C-arm system
      (Axiom Artis; Siemens AG, Germany) equipped with a flat detector of 40 x 30
      cm(2). The merging approach conserved standard image noise levels and the CNR in
      areas without cardiac motion, whereas image noise in pericardial lung regions and
      in the heart was increased compared with standard images. Motion artefacts in the
      heart and in the lung areas close to the heart are significantly reduced in the
      material-selective images when compared with a standard non-gated subtraction.

PMID- 19098085
TI  - Myocardial delayed contrast-enhanced MRI: relationships between various enhancing
      patterns and myocardial diseases.
AB  - The concentration of MR contrast agents is relatively high in abnormal myocardial
      tissue, with increased extravascular space and/or abnormal contrast wash-in and
      wash-out characteristics. Based on this mechanism, myocardial delayed contrast
      enhanced MRI has been increasingly used to detect myocardial damage. Delayed
      enhancement (DE) can be seen in various components, such as fibrosis, protein
      infiltration or possibly myocardial disarray with disorganized myocardial fibre
      packing. Therefore, DE can be seen in various myocardial diseases, each of which
      has a characteristic DE pattern. Knowledge of the relationships among various DE
      patterns and myocardial diseases is useful for differential diagnosis and
      management.

PMID- 19098086
TI  - Spectrum of imaging findings in melioidosis.
AB  - This pictorial review aims to highlight the clinical and imaging features of
      melioidosis in various organ systems. The patients were from two centres: one in
      Thailand and one in Singapore. The annual average incidence of melioidosis is
      estimated to be 4.4 in 100 000 in north-eastern Thailand and 1.7 in 100 000 in
      Singapore. Melioidosis affects many different organs and produces a spectrum of
      imaging features. The lung is the most frequently involved organ and, on
      radiographs and computed tomography, melioidosis may manifest as acute pulmonary
      consolidation, multiple nodules and abscesses. The finding of multiple small
      discrete abscesses in both the liver and the spleen is highly suggestive of
      visceral melioidosis and is best diagnosed on ultrasonography and computed
      tomography. Bone and soft tissue musculoskeletal involvement is usually part of
      disseminated melioidosis, with changes being seen on radiographs and MRI.
      Although imaging findings of melioidosis are not specific, this infection
      requires a high index of clinical suspicion, particularly in patients with pre
      disposing comorbidities, such as diabetes mellitus, chronic renal failure,
      alcoholism or malignancy, those who are immunosuppressed as the result of either
      diseases or drug treatment, and those living in or with a history of travel to
      endemic areas.

PMID- 19098087
TI  - Computational cardiac atlases: from patient to population and back.
AB  - Integrative models of cardiac physiology are important for understanding disease
      and planning intervention. Multimodal cardiovascular imaging plays an important
      role in defining the computational domain, the boundary/initial conditions, and
      tissue function and properties. Computational models can then be personalized
      through information derived from in vivo and, when possible, non-invasive images.
      Efforts are now established to provide Web-accessible structural and functional
      atlases of the normal and pathological heart for clinical, research and
      educational purposes. Efficient and robust statistical representations of cardiac
      morphology and morphodynamics can thereby be obtained, enabling quantitative
      analysis of images based on such representations. Statistical models of shape and
      appearance can be built automatically from large populations of image datasets by
      minimizing manual intervention and data collection. These methods facilitate
      statistical analysis of regional heart shape and wall motion characteristics
      across population groups, via the application of parametric mathematical
      modelling tools. These parametric modelling tools and associated ontological
      schema also facilitate data fusion between different imaging protocols and
      modalities as well as other data sources. Statistical priors can also be used to
      support cardiac image analysis with applications to advanced quantification and
      subject-specific simulations of computational physiology.

PMID- 19098088
TI  - Effect of chronic exercise on DNA fragmentation and on lipid profiles in rat
      skeletal muscle.
AB  - The concentration and fatty acid composition of phospholipids in animal cells are
      important determinants of membrane function. Membrane function may influence
      apoptosis, a biological process that is crucial for the normal development and
      function of the body. Few and conflicting data exist regarding the effect of
      chronic exercise on apoptosis in skeletal muscle, and no data exist regarding the
      effect of chronic exercise on the fatty acid composition of individual muscle
      phospholipids. We therefore examined the effects of 8 weeks of voluntary wheel
      running on DNA fragmentation (an index of apoptosis) and on the concentration and
      fatty acid composition of individual muscle phospholipids and ceramide (a lipid
      involved in apoptotic signalling) in rat gastrocnemius muscle by comparing 11
      trained and 14 untrained male Wistar rats. The trained animals had significantly
      (P < 0.05) higher cytochrome c oxidase activity (an index of aerobic adaptation)
      and lower phosphatidyl inositol concentration compared with their untrained
      counterparts. Groups did not differ in DNA fragmentation or any other lipid
      parameter. Our findings suggest that chronic wheel running did not affect
      apoptosis or the concentration and fatty acid composition of most phospholipids
      and ceramide in rat gastrocnemius muscle. Given the participation of several
      phospholipids and ceramide in apoptotic signalling, it appears that the lack of
      changes in the lipid parameters is in agreement with the lack of change in DNA
      fragmentation with exercise.

PMID- 19098089
TI  - The Cardiac Physiome: perspectives for the future.
AB  - The Physiome Project, exemplified by the Cardiac Physiome, is now 10 years old.
      In this article, we review past progress and future challenges in developing a
      quantitative framework for understanding human physiology that incorporates both
      genetic inheritance and environmental influence. Despite the enormity of the
      challenge, which is certainly greater than that facing the pioneers of the human
      genome project 20 years ago, there is reason for optimism that real and
      accelerating progress is being made.

PMID- 19098090
TI  - Ricinosomes predict programmed cell death leading to anther dehiscence in tomato.
AB  - Successful development and dehiscence of the anther and release of pollen are
      dependent upon the programmed cell death (PCD) of the tapetum and other
      sporophytic tissues. Ultrastructural examination of the developing and dehiscing
      anther of tomato (Solanum lycopersicum) revealed that cells of the interlocular
      septum, the connective tissue, the middle layer/endothecium, and the epidermal
      cells surrounding the stomium all exhibit features consistent with progression
      through PCD. Ricinosomes, a subset of precursor protease vesicles that are unique
      to some incidents of plant PCD, were also present in all of these cell types.
      These novel organelles are known to harbor KDEL-tailed cysteine proteinases that
      act in the final stages of corpse processing following cell death. Indeed, a
      tomato KDEL-tailed cysteine proteinase, SlCysEP, was identified and its gene was
      cloned, sequenced, and characterized. SlCysEP transcript and protein were
      restricted to the anthers of the senescing tomato flower. Present in the
      interlocular septum and in the epidermal cells surrounding the stomium relatively
      early in development, SlCysEP accumulates later in the sporophytic tissues
      surrounding the locules as dehiscence ensues. At the ultrastuctural level,
      immunogold labeling localized SlCysEP to the ricinosomes within the cells of
      these tissues, but not in the tapetum. It is suggested that the accumulation of
      SlCysEP and the appearance of ricinosomes act as very early predictors of cell
      death in the tomato anther.

PMID- 19098091
TI  - Multidrug and toxic compound extrusion-type transporters implicated in vacuolar
      sequestration of nicotine in tobacco roots.
AB  - Nicotine is a major alkaloid accumulating in the vacuole of tobacco (Nicotiana
      tabacum), but the transporters involved in the vacuolar sequestration are not
      known. We here report that tobacco genes (NtMATE1 and NtMATE2) encoding
      transporters of the multidrug and toxic compound extrusion (MATE) family are
      coordinately regulated with structural genes for nicotine biosynthesis in the
      root, with respect to spatial expression patterns, regulation by NIC regulatory
      loci, and induction by methyl jasmonate. Subcellular fractionation, immunogold
      electron microscopy, and expression of a green fluorescent protein fusion protein
      all suggested that these transporters are localized to the vacuolar membrane.
      Reduced expression of the transporters rendered tobacco plants more sensitive to
      the application of nicotine. In contrast, overexpression of NtMATE1 in cultured
      tobacco cells induced strong acidification of the cytoplasm after jasmonate
      elicitation or after the addition of nicotine under nonelicited conditions.
      Expression of NtMATE1 in yeast (Saccharomyces cerevisiae) cells compromised the
      accumulation of exogenously supplied nicotine into the yeast cells. The results
      imply that these MATE-type proteins transport tobacco alkaloids from the cytosol
      into the vacuole in exchange for protons in alkaloid-synthesizing root cells.

PMID- 19098092
TI  - Ectopic expression of VvMybPA2 promotes proanthocyanidin biosynthesis in
      grapevine and suggests additional targets in the pathway.
AB  - Grapevine (Vitis vinifera) proanthocyanidins contribute to plant defense
      mechanisms against biotic stress and also play a critical role in organoleptic
      properties of wine. In grapevine berry, these compounds are mainly accumulated in
      exocarps and seeds in the very early stages of development. A previous study has
      already identified VvMybPA1 as the first transcription factor involved in the
      regulation of the proanthocyanidin pathway during seed development in grapevine.
      A novel Myb factor, VvMybPA2, which is described in this study, is in contrast
      mainly expressed in the exocarp of young berries and in the leaves. This
      transcription factor shows very high protein sequence homology with other plant
      Myb factors, which regulate flavonoid biosynthesis. Ectopic expression of either
      VvMybPA1 or VvMybPA2 in grapevine hairy roots induced qualitative and
      quantitative changes of the proanthocyanidin profiles. High-throughput
      transcriptomic analyses of transformed grapevine organs identified a large set of
      putative targets of the VvMybPA1 and VvMybPA2 transcription factors. Both genes
      significantly activated enzymes of the flavonoid pathway, including anthocyanidin
      reductase and leucoanthocyanidin reductase 1, the specific terminal steps in the
      biosynthesis of epicatechin and catechin, respectively, but not
      leucoanthocyanidin reductase 2. The functional annotation of the genes whose
      expression was modified revealed putative new actors of the proanthocyanidin
      pathway, such as glucosyltransferases and transporters.

PMID- 19098093
TI  - Overexpression of flavodoxin in bacteroids induces changes in antioxidant
      metabolism leading to delayed senescence and starch accumulation in alfalfa root
      nodules.
AB  - Sinorhizobium meliloti cells were engineered to overexpress Anabaena variabilis
      flavodoxin, a protein that is involved in the response to oxidative stress.
      Nodule natural senescence was characterized in alfalfa (Medicago sativa) plants
      nodulated by the flavodoxin-overexpressing rhizobia or the corresponding control
      bacteria. The decline of nitrogenase activity and the nodule structural and
      ultrastructural alterations that are associated with nodule senescence were
      significantly delayed in flavodoxin-expressing nodules. Substantial changes in
      nodule antioxidant metabolism, involving antioxidant enzymes and ascorbate
      glutathione cycle enzymes and metabolites, were detected in flavodoxin-containing
      nodules. Lipid peroxidation was also significantly lower in flavodoxin-expressing
      nodules than in control nodules. The observed amelioration of the oxidative
      balance suggests that the delay in nodule senescence was most likely due to a
      role of the protein in reactive oxygen species detoxification. Flavodoxin
      overexpression also led to high starch accumulation in nodules, without reduction
      of the nitrogen-fixing activity.

PMID- 19098094
TI  - Regulation of respiration and fermentation to control the plant internal oxygen
      concentration.
AB  - Plant internal oxygen concentrations can drop well below ambient even when the
      plant grows under optimal conditions. Using pea (Pisum sativum) roots, we show
      how amenable respiration adapts to hypoxia to save oxygen when the oxygen
      availability decreases. The data cannot simply be explained by oxygen being
      limiting as substrate but indicate the existence of a regulatory mechanism,
      because the oxygen concentration at which the adaptive response is initiated is
      independent of the actual respiratory rate. Two phases can be discerned during
      the adaptive reaction: an initial linear decline of respiration is followed by a
      nonlinear inhibition in which the respiratory rate decreased progressively faster
      upon decreasing oxygen availability. In contrast to the cytochrome c pathway, the
      inhibition of the alternative oxidase pathway shows only the linear component of
      the adaptive response. Feeding pyruvate to the roots led to an increase of the
      oxygen consumption rate, which ultimately led to anoxia. The importance of
      balancing the in vivo pyruvate availability in the tissue was further
      investigated. Using various alcohol dehydrogenase knockout lines of Arabidopsis
      (Arabidopsis thaliana), it was shown that even under aerobic conditions, alcohol
      fermentation plays an important role in the control of the level of pyruvate in
      the tissue. Interestingly, alcohol fermentation appeared to be primarily induced
      by a drop in the energy status of the tissue rather than by a low oxygen
      concentration, indicating that sensing the energy status is an important
      component of optimizing plant metabolism to changes in the oxygen availability.

PMID- 19098095
TI  - A pollen protein, NaPCCP, that binds pistil arabinogalactan proteins also binds
      phosphatidylinositol 3-phosphate and associates with the pollen tube endomembrane
      system.
AB  - As pollen tubes grow toward the ovary, they are in constant contact with the
      pistil extracellular matrix (ECM). ECM components are taken up during growth, and
      some pistil molecules exert their effect inside the pollen tube. For instance,
      the Nicotiana alata 120-kD glycoprotein (120K) is an abundant arabinogalactan
      protein that is taken up from the ECM; it has been detected in association with
      pollen tube vacuoles, but the transport pathway between these compartments is
      unknown. We recently identified a pollen C2 domain-containing protein (NaPCCP)
      that binds to the carboxyl-terminal domain of 120K. As C2 domain proteins mediate
      protein-lipid interactions, NaPCCP could function in intracellular transport of
      120K in pollen tubes. Here, we describe binding studies showing that the NaPCCP
      C2 domain is functional and that binding is specific for phosphatidylinositol 3
      phosphate. Subcellular fractionation, immunolocalization, and live imaging
      results show that NaPCCP is associated with the plasma membrane and internal
      pollen tube vesicles. Colocalization between an NaPCCPgreen fluorescent protein
      fusion and internalized FM4-64 suggest an association with the endosomal system.
      NaPCCP localization is altered in pollen tubes rejected by the self
      incompatibility mechanism, but our hypothesis is that it has a general function
      in the transport of endocytic cargo rather than a specific function in self
      incompatibility. NaPCCP represents a bifunctional protein with both
      phosphatidylinositol 3-phosphate- and arabinogalactan protein-binding domains.
      Therefore, it could function in the transport of pistil ECM proteins in the
      pollen tube endomembrane system.

PMID- 19098096
TI  - Adaptive protein evolution grants organismal fitness by improving catalysis and
      flexibility.
AB  - Protein evolution is crucial for organismal adaptation and fitness. This process
      takes place by shaping a given 3-dimensional fold for its particular biochemical
      function within the metabolic requirements and constraints of the environment.
      The complex interplay between sequence, structure, functionality, and stability
      that gives rise to a particular phenotype has limited the identification of
      traits acquired through evolution. This is further complicated by the fact that
      mutations are pleiotropic, and interactions between mutations are not always
      understood. Antibiotic resistance mediated by beta-lactamases represents an
      evolutionary paradigm in which organismal fitness depends on the catalytic
      efficiency of a single enzyme. Based on this, we have dissected the structural
      and mechanistic features acquired by an optimized metallo-beta-lactamase (MbetaL)
      obtained by directed evolution. We show that antibiotic resistance mediated by
      this enzyme is driven by 2 mutations with sign epistasis. One mutation stabilizes
      a catalytically relevant intermediate by fine tuning the position of 1 metal ion;
      whereas the other acts by augmenting the protein flexibility. We found that
      enzyme evolution (and the associated antibiotic resistance) occurred at the
      expense of the protein stability, revealing that MbetaLs have not exhausted their
      stability threshold. Our results demonstrate that flexibility is an essential
      trait that can be acquired during evolution on stable protein scaffolds. Directed
      evolution aided by a thorough characterization of the selected proteins can be
      successfully used to predict future evolutionary events and design inhibitors
      with an evolutionary perspective.

PMID- 19098097
TI  - Discovery and revision of Arabidopsis genes by proteogenomics.
AB  - Gene annotation underpins genome science. Most often protein coding sequence is
      inferred from the genome based on transcript evidence and computational
      predictions. While generally correct, gene models suffer from errors in reading
      frame, exon border definition, and exon identification. To ascertain the error
      rate of Arabidopsis thaliana gene models, we isolated proteins from a sample of
      Arabidopsis tissues and determined the amino acid sequences of 144,079 distinct
      peptides by tandem mass spectrometry. The peptides corresponded to 1 or more of 3
      different translations of the genome: a 6-frame translation, an exon splice
      graph, and the currently annotated proteome. The majority of the peptides
      (126,055) resided in existing gene models (12,769 confirmed proteins), comprising
      40% of annotated genes. Surprisingly, 18,024 novel peptides were found that do
      not correspond to annotated genes. Using the gene finding program AUGUSTUS and
      5,426 novel peptides that occurred in clusters, we discovered 778 new protein
      coding genes and refined the annotation of an additional 695 gene models. The
      remaining 13,449 novel peptides provide high quality annotation (>99% correct)
      for thousands of additional genes. Our observation that 18,024 of 144,079
      peptides did not match current gene models suggests that 13% of the Arabidopsis
      proteome was incomplete due to approximately equal numbers of missing and
      incorrect gene models.

PMID- 19098098
TI  - Stochasticity and bistability in horizontal transfer control of a genomic island
      in Pseudomonas.
AB  - Genomic islands (GEI) comprise a recently recognized large family of potentially
      mobile DNA elements and play an important role in the rapid differentiation and
      adaptation of bacteria. Most importantly, GEIs have been implicated in the
      acquisition of virulence factors, antibiotic resistances or toxic compound
      metabolism. Despite detailed information on coding capacities of GEIs, little is
      known about the regulatory decisions in individual cells controlling GEI
      transfer. Here, we show how self-transfer of ICEclc, a GEI in Pseudomonas
      knackmussii B13 is controlled by a series of stochastic processes, the result of
      which is that only a few percent of cells in a population will excise ICEclc and
      launch transfer. Stochastic processes have been implicated before in producing
      bistable phenotypic transitions, such as sporulation and competence development,
      but never before in horizontal gene transfer (HGT). Bistability is instigated
      during stationary phase at the level of expression of an activator protein InrR
      that lays encoded on ICEclc, and then faithfully propagated to a bistable
      expression of the IntB13 integrase, the enzyme responsible for excision and
      integration of the ICEclc. Our results demonstrate how GEI of a very widespread
      family are likely to control their transfer rates. Furthermore, they help to
      explain why HGT is typically confined to few members within a population of
      cells. The finding that, despite apparent stochasticity, HGT rates can be
      modulated by external environmental conditions provides an explanation as to why
      selective conditions can promote DNA exchange.

PMID- 19098099
TI  - Two-step oligoclonal development of male germ cells.
AB  - During mouse development, primordial germ cells (PGCs) that give rise to the
      entire germ line are first identified within the proximal epiblast. However, long
      term tracing of the fate of the cells has not been done wherein all cells in and
      around the germ-cell lineage are identified. Also, quantitative estimates of the
      number of founder PGCs using different models have come up with various numbers.
      Here, we use tetrachimeric mice to show that the progenitor numbers for the
      entire germ line in adult testis, and for the initiating embryonic PGCs, are both
      4 cells. Although they proliferate to form polyclonal germ-cell populations in
      fetal and neonatal testes, germ cells that actually contribute to adult
      spermatogenesis originate from a small number of secondary founder cells that
      originate in the fetal period. The rest of the "deciduous" germ cells are lost,
      most likely by apoptosis, before the reproductive period. The second "actual"
      founder germ cells generally form small numbers of large monoclonal areas in
      testes by the reproductive period. Our results also demonstrate that there is no
      contribution of somatic cells to the male germ cell pool during development or in
      adulthood. These results suggest a model of 2-step oligoclonal development of
      male germ cells in mice, the second step distinguishing the heritable germ line
      from cells selected not to participate in forming the next generation.

PMID- 19098100
TI  - Bidirectional Ca2+-dependent control of mitochondrial dynamics by the Miro
      GTPase.
AB  - Calcium oscillations suppress mitochondrial movements along the microtubules to
      support on-demand distribution of mitochondria. To activate this mechanism,
      Ca(2+) targets a yet unidentified cytoplasmic factor that does not seem to be a
      microtubular motor or a kinase/phosphatase. Here, we have studied the dependence
      of mitochondrial dynamics on the Miro GTPases that reside in the mitochondria and
      contain two EF-hand Ca(2+)-binding domains, in H9c2 cells and primary neurons. At
      resting cytoplasmic [Ca(2+)] ([Ca(2+)](c)), movements of the mitochondria were
      enhanced by Miro overexpression irrespective of the presence of the EF-hands. The
      Ca(2+)-induced arrest of mitochondrial motility was also promoted by Miro
      overexpression and was suppressed when either the Miro were depleted or their EF
      hand was mutated. Miro also enhanced the fusion state of the mitochondria at
      resting [Ca(2+)](c) but promoted mitochondrial fragmentation at high [Ca(2+)](c).
      These effects of Miro on mitochondrial morphology seem to involve Drp1
      suppression and activation, respectively. In primary neurons, Miro also caused an
      increase in dendritic mitochondrial mass and enhanced mitochondrial calcium
      signaling. Thus, Miro proteins serve as a [Ca(2+)](c)-sensitive switch and
      bifunctional regulator for both the motility and fusion-fission dynamics of the
      mitochondria.

PMID- 19098101
TI  - Origin of the sharp boundary that discriminates positive and negative selection
      of thymocytes.
AB  - T lymphocytes play a key role in adaptive immunity and are activated by
      interactions of their T cell receptors (TCR) with peptides (p) derived from
      antigenic proteins bound to MHC gene products. The repertoire of T lymphocytes
      available in peripheral organs is tuned in the thymus. Immature T lymphocytes
      (thymocytes) interact with diverse endogenous peptides bound to MHC in the
      thymus. TCR expressed on thymocytes must bind weakly to endogenous pMHC (positive
      selection) but must not bind too strongly to them (negative selection) to emerge
      from the thymus. Negatively selecting pMHC ligands bind TCR with a binding
      affinity that exceeds a sharply defined (digital) threshold. In contrast, there
      is no sharp threshold separating positively selecting ligands from those that
      bind too weakly to elicit a response. We describe results of computer simulations
      and experiments, which suggest that the contrast between the characters of the
      positive and negative selection thresholds originates in differences in the way
      in which Ras proteins are activated by ligands of varying potency. The molecular
      mechanism suggested by our studies generates hypotheses for how genetic
      aberrations may dampen the digital negative selection response, with concomitant
      escape of autoimmune T lymphocytes from the thymus.

PMID- 19098102
TI  - Activity-independent and subunit-specific recruitment of functional AMPA
      receptors at neurexin/neuroligin contacts.
AB  - A combination of cell culture and animal studies has recently shown that adhesion
      between neurexins and neuroligins played important roles in synapse initiation,
      maturation, and function. Binding of neurexin-1beta to neuroligin-1 triggers the
      postsynaptic clustering of the scaffold postsynaptic density protein 95, but the
      composition and timing of accumulation of glutamate receptors at those nascent
      contacts remain unclear. Using glutamate iontophoresis and patch-clamp
      recordings, we identified functional AMPA receptors (AMPARs) and NMDA receptors
      at postsynaptic density protein 95 clusters induced by neurexin-1beta coated
      microspheres on primary hippocampal neurons. The recruitment of AMPARs occurred
      as early as 2 h after initial contact, and was not blocked by TTX/2-amino-5
      phosphovaleric acid (APV) treatment. The differential recruitment of recombinant
      subunits GluR1 and GluR2, as well as the absence of rectification in
      voltage/current curves, further indicate that neurexin/neuroligin contacts
      primarily recruit GluR2-containing AMPARs. Finally, by using glutamate un-caging
      and calcium imaging, we show that AMPARs participate in calcium entry at neurexin
      1beta induced post-synapses, most likely through the activation of voltage-gated
      calcium channels. Such rapid and activity-independent accumulation of functional
      AMPARs at neurexin-1beta-induced postsynapses points to a new role of AMPARs in
      synaptogenesis.

PMID- 19098103
TI  - Determination of cell fate selection during phage lambda infection.
AB  - Bacteriophage lambda infection of Escherichia coli can result in distinct cell
      fate outcomes. For example, some cells lyse whereas others survive as lysogens. A
      quantitative biophysical model of lambda infection supports the hypothesis that
      spontaneous differences in the timing of individual molecular events during
      lambda infection leads to variation in the selection of cell fates. Building from
      this analysis, the lambda lysis-lysogeny decision now serves as a paradigm for
      how intrinsic molecular noise can influence cellular behavior, drive
      developmental processes, and produce population heterogeneity. Here, we report
      experimental evidence that warrants reconsidering this framework. By using cell
      fractioning, plating, and single-cell fluorescent microscopy, we find that
      physical differences among cells present before infection bias lambda
      developmental outcomes. Specifically, variation in cell volume at the time of
      infection can be used to help predict cell fate: a approximately 2-fold increase
      in cell volume results in a 4- to 5-fold decrease in the probability of lysogeny.
      Other cell fate decisions now thought to be stochastic might also be determined
      by pre-existing variation.

PMID- 19098104
TI  - Functional comparison of RGS9 splice isoforms in a living cell.
AB  - Two isoforms of the GTPase-activating protein, regulator of G protein signaling 9
      (RGS9), control such fundamental functions as vision and behavior. RGS9-1
      regulates phototransduction in rods and cones, and RGS9-2 regulates dopamine and
      opioid signaling in the basal ganglia. To determine their functional differences
      in the same intact cell, we replaced RGS9-1 with RGS9-2 in mouse rods.
      Surprisingly, RGS9-2 not only supported normal photoresponse recovery under
      moderate light conditions but also outperformed RGS9-1 in bright light. This
      versatility of RGS9-2 results from its ability to inactivate the G protein,
      transducin, regardless of its effector interactions, whereas RGS9-1 prefers the G
      protein-effector complex. Such versatility makes RGS9-2 an isoform advantageous
      for timely signal inactivation across a wide range of stimulus strengths and may
      explain its predominant representation throughout the nervous system.

PMID- 19098105
TI  - Single-molecule DNA detection with an engineered MspA protein nanopore.
AB  - Nanopores hold great promise as single-molecule analytical devices and
      biophysical model systems because the ionic current blockades they produce
      contain information about the identity, concentration, structure, and dynamics of
      target molecules. The porin MspA of Mycobacterium smegmatis has remarkable
      stability against environmental stresses and can be rationally modified based on
      its crystal structure. Further, MspA has a short and narrow channel constriction
      that is promising for DNA sequencing because it may enable improved
      characterization of short segments of a ssDNA molecule that is threaded through
      the pore. By eliminating the negative charge in the channel constriction, we
      designed and constructed an MspA mutant capable of electronically detecting and
      characterizing single molecules of ssDNA as they are electrophoretically driven
      through the pore. A second mutant with additional exchanges of negatively-charged
      residues for positively-charged residues in the vestibule region exhibited a
      factor of approximately 20 higher interaction rates, required only half as much
      voltage to observe interaction, and allowed ssDNA to reside in the vestibule
      approximately 100 times longer than the first mutant. Our results introduce MspA
      as a nanopore for nucleic acid analysis and highlight its potential as an
      engineerable platform for single-molecule detection and characterization
      applications.

PMID- 19098106
TI  - Palmitoylation gates phosphorylation-dependent regulation of BK potassium
      channels.
AB  - Large conductance calcium- and voltage-gated potassium (BK) channels are
      important regulators of physiological homeostasis and their function is potently
      modulated by protein kinase A (PKA) phosphorylation. PKA regulates the channel
      through phosphorylation of residues within the intracellular C terminus of the
      pore-forming alpha-subunits. However, the molecular mechanism(s) by which
      phosphorylation of the alpha-subunit effects changes in channel activity are
      unknown. Inhibition of BK channels by PKA depends on phosphorylation of only a
      single alpha-subunit in the channel tetramer containing an alternatively spliced
      insert (STREX) suggesting that phosphorylation results in major conformational
      rearrangements of the C terminus. Here, we define the mechanism of PKA inhibition
      of BK channels and demonstrate that this regulation is conditional on the
      palmitoylation status of the channel. We show that the cytosolic C terminus of
      the STREX BK channel uniquely interacts with the plasma membrane via
      palmitoylation of evolutionarily conserved cysteine residues in the STREX insert.
      PKA phosphorylation of the serine residue immediately upstream of the conserved
      palmitoylated cysteine residues within STREX dissociates the C terminus from the
      plasma membrane, inhibiting STREX channel activity. Abolition of STREX
      palmitoylation by site-directed mutagenesis or pharmacological inhibition of
      palmitoyl transferases prevents PKA-mediated inhibition of BK channels. Thus,
      palmitoylation gates BK channel regulation by PKA phosphorylation. Palmitoylation
      and phosphorylation are both dynamically regulated; thus, cross-talk between
      these 2 major posttranslational signaling cascades provides a mechanism for
      conditional regulation of BK channels. Interplay of these distinct signaling
      cascades has important implications for the dynamic regulation of BK channels and
      physiological homeostasis.

PMID- 19098107
TI  - Structural basis for cross-resistance to ribosomal PTC antibiotics.
AB  - Clinically relevant antibiotics that target the ribosomal peptidyl transferase
      center (PTC), a highly conserved ribosomal region, exert their inhibitory action
      by exploiting the flexibility of PTC nucleotides, which trigger modulations of
      the shape of the antibiotic binding pocket. Resistance to these antibiotics was
      observed clinically and in vitro. Based on the crystal structures of the large
      ribosomal subunit from eubacterium suitable to represent pathogens in complex
      with these antibiotics, it was found that all nucleotides mediating resistance to
      PTC antibiotics cluster on one side of the PTC. Over half of the nucleotides
      affecting resistance reside in regions of lower sequence conservation, and are
      too distal to make Van der Waals interactions with the bound drugs. Alterations
      of the identity of these nucleotides may not lethally affect ribosome function,
      but can hamper antibiotic binding through changes in the conformation and
      flexibility of specific PTC nucleotides. Comparative analysis revealed properties
      likely to lead to cross-resistance and enabled their parameterization. As the
      same nucleotides are frequently involved in resistance to more than a single
      family of antibiotics, the common pattern explains medically observed cross
      resistance to PTC antibiotics and suggests the potential for a wider clinical
      threat.

PMID- 19098108
TI  - Improved competence after a palliative care course for internal medicine
      residents.
AB  - Residents report that they received inadequate teaching in palliative care and
      low levels of comfort and skills when taking care of dying patients. This study
      describes the effects of a problem-based palliative care course on perceived
      competence and knowledge in a representative Dutch cohort of residents in
      internal medicine. Before and after the course, we carried out a questionnaire
      survey and knowledge test in 91 residents. The results show that many residents
      felt they had limited competence or were incompetent when taking care of patients
      in the palliative care phase. This was particularly true with respect to
      communication concerning euthanasia and physician-assisted suicide or hastened
      death (86% and 85% respectively reported limited competence or incompetence).
      Participants reported that they received inadequate training in palliative care
      and believed that specific education would make them feel more competent. The
      number of times that residents were engaged in palliative care situations and the
      years of clinical experience had a positive influence on perceived competence.
      Participating in the course improved perceived competence and knowledge in
      palliative care. No correlation was found between perceived competence and
      knowledge of palliative care.

PMID- 19098109
TI  - Out-of-hours need for specialist palliative care face-to-face assessments.

PMID- 19098110
TI  - Palliative stage Parkinson's disease: patient and family experiences of health
      care services.
AB  - Little is known about the lived health-care experiences of persons living with
      palliative stage Parkinson's disease and the family members who care for them. An
      exploratory phenomenological investigation was adopted to understand
      participant's lived health-care experiences and the needs flowing from them.
      Three family groupings participated in semi-structured in-depth interviews.
      Interpretative phenomenological analysis revealed three main themes: missing
      information, being on your own, wanting and not wanting to know. Findings support
      previous research that indicate palliative care needs are not being met in our
      current health-care model and that palliative care services should be multi
      disciplinary team-based in order to provide comprehensive support to patients and
      families. Based on this current work, we are currently undertaking a
      comprehensive quantitative-based multi-disciplinary health-care service needs
      assessment of palliative stage PD patients with the goal to implement expanded
      services.

PMID- 19098111
TI  - LPS-induced autophagy is mediated by oxidative signaling in cardiomyocytes and is
      associated with cytoprotection.
AB  - Bacterial endotoxin lipopolysaccharide (LPS) is responsible for the multiorgan
      dysfunction that characterizes septic shock and is causal in the myocardial
      depression that is a common feature of endotoxemia in patients. In this setting
      the myocardial dysfunction appears to be due, in part, to the production of
      proinflammatory cytokines. A line of evidence also indicates that LPS stimulates
      autophagy in cardiomyocytes. However, the signal transduction pathway leading to
      autophagy and its role in the heart are incompletely characterized. In this work,
      we wished to determine the effect of LPS on autophagy and the physiological
      significance of the autophagic response. Autophagy was monitored morphologically
      and biochemically in HL-1 cardiomyocytes, neonatal rat cardiomyocytes, and
      transgenic mouse hearts after the administration of bacterial LPS or TNF-alpha.
      We observed that autophagy was increased after exposure to LPS or TNF-alpha,
      which is induced by LPS. The inhibition of TNF-alpha production by AG126
      significantly reduced the accumulation of autophagosomes both in cell culture and
      in vivo. The inhibition of p38 MAPK or nitric oxide synthase by pharmacological
      inhibitors also reduced autophagy. Nitric oxide or H(2)O(2) induced autophagy in
      cardiomyocytes, whereas N-acetyl-cysteine, a potent antioxidant, suppressed
      autophagy. LPS resulted in increased reactive oxygen species (ROS) production and
      decreased total glutathione. To test the hypothesis that autophagy might serve as
      a damage control mechanism to limit further ROS production, we induced autophagy
      with rapamycin before LPS exposure. The activation of autophagy by rapamycin
      suppressed LPS-mediated ROS production and protected cells against LPS toxicity.
      These findings support the notion that autophagy is a cytoprotective response to
      LPS-induced cardiomyocyte injury; additional studies are needed to determine the
      therapeutic implications.

PMID- 19098113
TI  - Right ventricular free wall circumferential strain reflects graded elevation in
      acute right ventricular afterload.
AB  - This study was designed to evaluate the concurrent changes in the right
      ventricular free wall (RVFW) movement in experimentally induced, acute mild,
      moderate, and severe right ventricle (RV) afterload conditions. In 14 open-chest
      pigs (weight 43 +/- 4 kg) with preserved pericardia, acute mild (>35 and <50
      mmHg), moderate (> or =50 and < or =60 mmHg), and severe (>60 mmHg) increases in
      RV systolic pressure (RVSP) were induced by constriction of the pulmonary artery.
      At each step, longitudinal, radial, and circumferential strains and strain rates
      were measured in both the RVFW and the interventricular septum. The mean RVSPs
      were 31.0 +/- 4.3 mmHg at baseline and 41.1 +/- 2.7 mmHg during mild, 52.7 +/-
      3.4 mmHg during moderate, and 61.7 +/- 1.6 mmHg during severe afterload
      conditions. The RVFW circumferential strains showed significant differences among
      baseline, mild, moderate, and severe afterload conditions (-10.5 +/- 3.9, -8.3 +/
      3.3, -5.4 +/- 2.7, and -7.5 +/- 5.3%, respectively, P = 0.008) and had
      significant linear correlation with RVSP (r = 0.636, P < 0.001) if the severe
      condition was excluded. Decrease of the RVFW circumferential strain magnitude is
      the most distinct response in acute mild and moderate RV afterload that could aid
      in detection of clinical conditions associated with acutely increasing RV
      afterload.

PMID- 19098112
TI  - Glucosamine improves cardiac function following trauma-hemorrhage by increased
      protein O-GlcNAcylation and attenuation of NF-{kappa}B signaling.
AB  - We have previously demonstrated that in a rat model of trauma-hemorrhage (T-H),
      glucosamine administration during resuscitation improved cardiac function,
      reduced circulating levels of inflammatory cytokines, and increased tissue levels
      of O-linked N-acetylglucosamine (O-GlcNAc) on proteins. The mechanism(s) by which
      glucosamine mediated its protective effect were not determined; therefore, the
      goal of this study was to test the hypothesis that glucosamine treatment
      attenuated the activation of the nuclear factor-kappaB (NF-kappaB) signaling
      pathway in the heart via an increase in protein O-GlcNAc levels. Fasted male rats
      were subjected to T-H by bleeding to a mean arterial blood pressure of 40 mmHg
      for 90 min followed by resuscitation. Glucosamine treatment during resuscitation
      significantly attenuated the T-H-induced increase in cardiac levels of TNF-alpha
      and IL-6 mRNA, IkappaB-alpha phosphorylation, NF-kappaB, NF-kappaB DNA binding
      activity, ICAM-1, and MPO activity. LPS (2 microg/ml) increased the levels of
      IkappaB-alpha phosphorylation, TNF-alpha, ICAM-1, and NF-kappaB in primary
      cultured cardiomyocytes, which was significantly attenuated by glucosamine
      treatment and overexpression of O-GlcNAc transferase; both interventions also
      significantly increased O-GlcNAc levels. In contrast, the transfection of
      neonatal rat ventricular myocytes with OGT small-interfering RNA decreased O
      GlcNAc transferase and O-GlcNAc levels and enhanced the LPS-induced increase in
      IkappaB-alpha phosphorylation. Glucosamine treatment of macrophage cell line RAW
      264.7 also increased O-GlcNAc levels and attenuated the LPS-induced activation of
      NF-kappaB. These results demonstrate that the modulation of O-GlcNAc levels
      alters the response of cardiomyocytes to the activation of the NF-kappaB pathway,
      which may contribute to the glucosamine-mediated improvement in cardiac function
      following hemorrhagic shock.

PMID- 19098114
TI  - N-acetyl-seryl-aspartyl-lysyl-proline prevents cardiac remodeling and dysfunction
      induced by galectin-3, a mammalian adhesion/growth-regulatory lectin.
AB  - Galectin-3 (Gal-3) is secreted by activated macrophages. In hypertension, Gal-3
      is a marker for hypertrophic hearts prone to develop heart failure. Gal-3 infused
      in pericardial sac leads to cardiac inflammation, remodeling, and dysfunction. N
      acetyl-seryl-aspartyl-lysyl-proline (Ac-SDKP), a naturally occurring
      tetrapeptide, prevents and reverses inflammation and collagen deposition in the
      heart in hypertension and heart failure postmyocardial infarction. In the present
      study, we hypothesize that Ac-SDKP prevents Gal-3-induced cardiac inflammation,
      remodeling, and dysfunction, and these effects are mediated by the transforming
      growth factor (TGF)-beta/Smad3 signaling pathway. Adult male rats were divided
      into four groups and received the following intrapericardial infusion for 4 wk:
      1) vehicle (saline, n = 8); 2) Ac-SDKP (800 microg x kg(-1) x day(-1), n = 8); 3)
      Gal-3 (12 microg/day, n = 7); and 4) Ac-SDKP + Gal-3 (n = 7). Left ventricular
      ejection fraction, cardiac output, and transmitral velocity were measured by
      echocardiography; inflammatory cell infiltration, cardiomyocyte hypertrophy, and
      collagen deposition in the heart by histological and immunohistochemical
      staining; and TGF-beta expression and Smad3 phosphorylation by Western blot. We
      found that, in the left ventricle, Gal-3 1) enhanced macrophage and mast cell
      infiltration, increased cardiac interstitial and perivascular fibrosis, and
      causes cardiac hypertrophy; 2) increased TGF-beta expression and Smad3
      phosphorylation; and 3) decreased negative change in pressure over time response
      to isoproterenol challenge, ratio of early left ventricular filling phase to
      atrial contraction phase, and left ventricular ejection fraction. Ac-SDKP
      partially or completely prevented these effects. We conclude that Ac-SDKP
      prevents Gal-3-induced cardiac inflammation, fibrosis, hypertrophy, and
      dysfunction, possibly via inhibition of the TGF-beta/Smad3 signaling pathway.

PMID- 19098115
TI  - Roles of Cx43-associated protein kinases in suppression of gap junction-mediated
      chemical coupling by ischemic preconditioning.
AB  - Ischemic preconditioning (PC) suppresses chemical coupling of cardiomyocytes via
      gap junctions (GJs) during ischemia, which is an adjunct mechanism of protection.
      The aim of this study was to characterize roles of protein kinases in PC-induced
      GJ modulation. In isolated rat hearts, ventricular tissues were sampled before
      and after ischemia with or without PC, and intercalated disc-rich fractions were
      separated for immunoprecipitation and immunoblotting. Levels of protein kinase C
      (PKC)-epsilon, p38mitogen-activated protein kinase (MAPK)-alpha, and Src
      coimmunoprecipitated with connexin-43 (Cx43) were increased after ischemia,
      whereas p38MAPKbeta was not detected in the Cx43 immunoprecipitates. PC did not
      modify the level of Cx43-Src complex after ischemia. However, PC enhanced Cx43
      PKCepsilon complex formation, which was abolished by PKCepsilon translocation
      inhibitory peptide (TIP). In contrast, PC reduced Cx43-p38MAPKalpha complex level
      and p38MAPK activity in the Cx43 immunoprecipitates after ischemia. The effect of
      PC on Cx43-p38MAPKalpha interaction was mimicked by SB-203580, a p38MAPK
      inhibitor. PC reduced permeability of GJs to Lucifer yellow in the myocardium at
      25 min after ischemia, and this effect was abolished by PKCepsilon-TIP. SB-203580
      increased the GJ permeability at 15 min after ischemia compared with that in
      untreated controls, but the difference became insignificant 25 min after
      ischemia. In conclusion, PC has distinct effects on interaction of GJ Cx43 with
      PKCepsilon, p38MAPKalpha, and Src during ischemia. Suppression of GJ permeability
      during ischemia by PC is primarily achieved by enhanced interaction of Cx43 with
      PKCepsilon, which overwhelms the counterbalancing effect of reduced Cx43
      p38MAPKalpha interaction.

PMID- 19098116
TI  - Recreational soccer is an effective health-promoting activity for untrained men.
AB  - To examine the effects of regular participation in recreational soccer on health
      profile, 36 healthy untrained Danish men aged 20-43 years were randomised into a
      soccer group (SO; n = 13), a running group (RU; n = 12) and a control group (CO;
      n = 11). Training was performed for 1 h two or three times per week for 12 weeks;
      at an average heart rate of 82% (SEM 2%) and 82% (1%) of HR(max) for SO and RU,
      respectively. During the 12 week period, maximal oxygen uptake increased (p<0.05)
      by 13% (3%) and 8% (3%) in SO and RU, respectively. In SO, systolic and diastolic
      blood pressure were reduced (p<0.05) from 130 (2) to 122 (2) mm Hg and from 77
      (2) to 72 (2) mm Hg, respectively, after 12 weeks, with similar decreases
      observed for RU. After the 12 weeks of training, fat mass was 3.0% (2.7 (0.6) kg)
      and 1.8% (1.8 (0.4) kg) lower (p<0.05) for SO and RU, respectively. Only SO had
      an increase in lean body mass (1.7 (0.4) kg, p<0.05), an increase in lower
      extremity bone mass (41 (8) g, p<0.05), a decrease in LDL-cholesterol (2.7 (0.2)
      to 2.3 (0.2) mmol/l; p<0.05) and an increase (p<0.05) in fat oxidation during
      running at 9.5 km/h. The number of capillaries per muscle fibre was 23% (4%) and
      16% (7%) higher (p<0.05) in SO and RU, respectively, after 12 weeks. No changes
      in any of the measured variables were observed for CO. In conclusion,
      participation in regular recreational soccer training, organised as small-sided
      drills, has significant beneficial effects on health profile and physical
      capacity for untrained men, and in some aspects it is superior to frequent
      moderate-intensity running.

PMID- 19098117
TI  - Metabolic syndrome pathophysiology and clinical presentation.
AB  - Metabolic syndrome is a relatively new definition, designed to help the health
      care practitioner to easily identify people at risk for the development of
      cardiovascular disease and diabetes. With the obesity epidemic, we are witnessing
      an epidemic of multiple-risk patients. Insulin resistance is the perceived
      pathophysiology of metabolic syndrome and defines its clinical presentation.
      Hypertension, dyslipedemia, polycystic ovarian syndrome, fatty liver disease, pre
      diabetes, sleep and breathing disorder, certain cancers, and cognitive impairment
      are many of the presentations of the syndrome; patients with any of these
      conditions are at a high risk of developing cardiovascular disease and diabetes.
      The metabolic syndrome helps identify people at risk to allow early intervention
      for prevention. Lifestyle modification is the most important part of the
      management of people with the syndrome. Lately medications--though none approved
      by the U.S. Food and Drug Administration (FDA)--have been recommended by major
      medical societies when lifestyle modification is not enough or when it fails.

PMID- 19098118
TI  - In vivo/ex vivo and in situ assays used in cancer research: a brief review.
AB  - Predicting whether a potential new anticancer agent will have a positive
      therapeutic index in patients remains a challenge. This brief review provides
      examples of preclinical in vivo/ex vivo and in situ assays used to assess the
      therapeutic potential of experimental anticancer therapeutics. Excision assays
      involving removal of tumor, bone marrow, and other tissues from the host after
      treatment to determine the effects of therapy in ex vivo assays are important
      preclinical tools. The survival of malignant cells from tumors treated in vivo
      and then excised is often determined by colony formation (CFU) in culture. When
      mice bearing in vivo alkylating agent-resistant tumors were treated with
      anticancer drugs such as cyclophosphamide, the survival pattern of bone marrow
      granulocyte-macrophage-colony forming units (CFU-GM) paralleled tumor cell
      survival. When TNP-470 and minocycline, an antiangiogenic combination, were added
      to treatment with cytotoxic anticancer therapies, tumor response markedly
      increased. TNP-470/minocycline-treated mice had higher tissue drug levels than
      did mice treated with the drug alone. Enzastaurin, an antiangiogenic protein
      kinase Cbeta inhibitor, treatment decreased intratumoral vessels to one half to
      one quarter of controls. Simultaneous and sequential treatment regimens with
      enzastaurin and BCNU delayed tumor growth and increased lifespan in mice bearing
      subcutaneous or intracranial human T98G glioblastoma multiforme. Both TNP-470 and
      enzastaurin have undergone clinical trials. Enzastaurin is currently in Phase III
      clinical trials.

PMID- 19098119
TI  - Using actigraphy to evaluate parental report of abnormal sleep patterns in
      children.

PMID- 19098120
TI  - Quantification of focal adhesion kinase activation loop phosphorylation as a
      biomarker of Src activity.
AB  - A recently developed stable isotope dilution liquid chromatography-multiple
      reaction/mass spectrometry method to quantify focal adhesion kinase (FAK)
      activation loop phosphorylation was used to study endogenous Src kinase activity.
      This revealed that bis-phosphorylated pTyr(576)/Tyr(577)-FAK was a biomarker of
      Src activity and inactivation in vitro and in cell culture. Mouse embryonic
      fibroblasts (MEFs) expressing endogenous Src family kinases contained 65%
      unmodified Tyr(576)/Tyr(577), 33% mono-phosphorylated-pTyr(576)-FAK, and 6% bis
      phosphorylated-pTyr(576)/pTyr(577)-FAK. In contrast, MEFs expressing oncogenic
      Y(529)FSrc contained 38% unmodified Tyr(576)/Tyr(577)-FAK, 29% mono
      phosphorylated-pTyr(576)-FAK, and 19% bis-phosphorylated-pTyr(576)/pTyr(577)-FAK.
      This new method has made it possible to accurately determine the absolute amounts
      of FAK phosphorylation that occur after Src inhibition in cell culture and in
      vitro with increasing concentrations of the Src inhibitor N-(5-chloro-1,3
      benzodioxol-4-yl)-7-[2-(4-methylpiperazin-1-yl)ethoxy]-5-(tetrahydro-2H-pyran-4
      yloxy)quinazolin-4-amine (AZD0530). Phosphorylation of FAK at Tyr(576)/Tyr(577)
      was inhibited by AZD0530 in a dose-dependent manner both in cell culture and in
      vitro. However, there was a substantial difference in the ability of AZD0530 to
      inhibit Src that was constitutively activated in a cellular context (IC(50) =
      2.12 muM) compared with the isolated enzyme (IC(50) = 0.14 muM). When normal MEFs
      and Y(529)FSrc-expressing MEFs were treated with pervanadate (a global
      phosphatase inhibitor), pTyr(576)/pTyr(577)-FAK accounted for almost 60% of the
      total FAK present in the cells. This suggests that activation loop
      phosphorylation is regulated by tyrosine phosphatases. These results confirm that
      FAK phosphorylation is a useful biomarker of Src inhibition in vivo. The accuracy
      and specificity of stable isotope dilution liquid chromatography-mass
      spectrometry methodology offers significant advantages over current
      immunochemical approaches for monitoring Src activity.

PMID- 19098121
TI  - Molecular mechanisms of corticotropin-releasing factor receptor-induced calcium
      signaling.
AB  - The molecular mechanisms governing calcium signal transduction of corticotropin
      releasing factor (CRF) receptors CRF(1) and CRF(2(a)) stably expressed in human
      embryonic kidney (HEK) 293 cells were investigated. Calcium signaling strictly
      depended on intracellular calcium sources, and this is the first study to
      establish a prominent contribution of the three major G-protein families to CRF
      receptor-mediated calcium signaling. Overexpression of Galpha(q/11) and
      Galpha(16) led to leftward shifts of the agonist concentration-response curves.
      Blockade of Galpha(q/11) proteins by the small interfering RNA (siRNA) technology
      partially reduced agonist-mediated calcium responses in CRF(1)- and CRF(2(a))
      expressing HEK293 cells, thereby proving a contribution of the G(q) protein
      family. A small but significant inhibition of calcium signaling was recorded by
      pharmacological inhibition of G(i/o) proteins with pertussis toxin treatment.
      This effect was mediated by direct binding of Gbetagamma subunits to
      phospholipase C. G(i/o) inhibition also elevated cAMP responses in CRF receptor
      overexpressing HEK293 cells and in Y79 retinoblastoma cells endogenously
      expressing human CRF(1) and CRF(2(a)) receptors, thereby demonstrating natural
      coupling of G(i) proteins to both CRF receptors. The strongest reduction of CRF
      receptor-mediated calcium mobilization was noted when blocking the G(s) signaling
      protein either by cholera toxin or by siRNA. It is noteworthy that simultaneous
      inhibition of two G-proteins shed light on the additive effects of G(s) and G(q)
      on the calcium signaling and, hence, that they act in parallel. On the other
      hand, G(i) coupling required prior G(s) activation.

PMID- 19098123
TI  - Virulence factors of Staphylococcus aureus induce Erk-MAP kinase activation and c
      Fos expression in S9 and 16HBE14o- human airway epithelial cells.
AB  - Part of the innate defense of bronchial epithelia against bacterial colonization
      is regulated secretion of salt, water, and mucus as well as defensins and
      cytokines involving MAP kinase activation and alterations in early gene
      expression. We tested two different types of immortalized human airway epithelial
      cells (S9, 16HBE14o-) for activation of Erk-type MAP kinases and for expression
      of c-Fos on treatment with Staphylococcus aureus culture supernatants from the
      stationary growth phase [optical density (OD)(540 nm) = 10] or with recombinant
      S. aureus hemolysins A and B (Hla, Hlb). OD10 supernatants activated Erk-type MAP
      kinases and c-Fos expression in a concentration-dependent manner. Hla induced Erk
      type kinase phosphorylation in S9 but not in 16HBE14o- cells. Hlb induced Erk
      activation in either cell type. Basal and stimulated levels of Erk-type MAP
      kinase phosphorylation were sensitive to the Mek1 inhibitor PD-98059, indicating
      that the bacterial products activated the entire signaling cascade that
      coregulates IL-8 induction and secretion. While c-Fos expression was enhanced by
      OD10 supernatants, Hla, and Hlb in S9 cells, 16HBE14o- cells responded to OD10
      supernatant and Hlb but not to Hla. In S9 cells, PD-98059 suppressed c-Fos
      upregulation by OD10 supernatant, Hla, or Hlb, indicating that c-Fos expression
      requires activation of Erk-type MAP kinases. In 16HBE14o- cells, however, c-Fos
      expression by OD10 supernatant was sensitive to PD-98059, while that induced by
      Hlb was not. This indicates that ingredients of OD10 supernatants other than Hla
      or Hlb are activating Erk-type MAP kinases in 16HBE14o- cells and that other
      intracellular signaling systems apart from Erk-type MAP kinases contribute to Hlb
      mediated regulation of c-Fos. Thus interaction of bacterial factors with airway
      epithelial cells may be highly cell type specific.

PMID- 19098122
TI  - A juxtamembrane mutation in the N terminus of the dopamine transporter induces
      preference for an inward-facing conformation.
AB  - The human dopamine transporter (hDAT) regulates synaptic dopamine (DA) levels and
      is the site of action of abused and therapeutic drugs. Here we study the effect
      of a threonine residue (Thr62 in hDAT) that is highly conserved within a
      canonical phosphorylation site (RETW) in the juxtamembrane N-terminal region of
      monoamine transporters. In stably transfected human embryonic kidney 293T cells,
      expression of T62D-hDAT was reduced compared with hDAT or T62A-hDAT. T62D-hDAT
      displayed dramatically reduced [(3)H]dopamine up-take but exhibited a higher
      basal dopamine efflux compared with hDAT or T62A-hDAT, as determined by
      measurements of [(3)H]dopamine efflux and amperometry. The high constitutive
      efflux in T62D-hDAT precluded the measurement of amphetamine-stimulated
      [(3)H]dopamine efflux, but when dopamine was added internally into voltage
      clamped T62D-hDAT cells, amphetamine-induced efflux comparable with hDAT was
      detected by amperometry. In accordance with findings that Zn(2+) can rescue
      reduced DA uptake in mutant transporters that are predominantly inward-facing,
      micromolar concentrations of Zn(2+) markedly potentiated [(3)H]dopamine uptake in
      T62D-hDAT and permitted the measurement of amphetamine-stimulated dopamine
      efflux. These results suggest that T62D-hDAT prefers an inward-facing
      conformation in the transition between inward- and outward-facing conformations.
      For T62A-hDAT, however, the measured 50% reduction in both [(3)H]dopamine uptake
      and [(3)H]dopamine efflux was consistent with a slowed transition between inward-
      and outward-facing conformations. The mechanism underlying the important
      functional role of Thr62 in hDAT activity suggested by these findings is examined
      in a structural context using dynamic simulations of a three-dimensional
      molecular model of DAT.

PMID- 19098124
TI  - Myeloid cells control termination of lung inflammation through the NF-kappaB
      pathway.
AB  - Although acute lung inflammation in response to local or systemic infection
      involves myeloid and nonmyeloid cells, the interplay between different cell types
      remains poorly defined. Since NF-kappaB is a key transcription factor for innate
      immunity, we investigated whether dysregulated NF-kappaB activation in myeloid
      cells impacts inflammatory signaling in nonmyeloid cells and generation of
      neutrophilic lung inflammation in response to systemic endotoxemia. We generated
      bone marrow chimeras by fetal liver transplantation of cells deficient in
      IkappaBalpha or p50 into lethally irradiated NF-kappaB reporter transgenic mice.
      No differences were apparent between bone marrow chimeras in the absence of an
      inflammatory stimulus; however, following intraperitoneal injection of
      Escherichia coli lipopolysaccharide (LPS), IkappaBalpha- or p50-deficient bone
      marrow chimeras showed increased NF-kappaB activation in nonhematopoietic cells,
      exaggerated neutrophilic inflammation, and higher mortality compared with
      untransplanted reporter mice and wild-type bone marrow chimeras. Primary bone
      marrow-derived macrophages (BMDM) from IkappaBalpha(-/-) or p50(-/-) exhibited
      increased NF-kappaB activation and macrophage inflammatory protein-2 production
      after LPS treatment compared with wild-type cells, and coculture of BMDM with
      lung epithelial (A549) cells resulted in increased NF-kappaB activation in A549
      cells and excess IL-8 production by these epithelial cells. These studies
      indicate an important role for inhibitory members of the NF-kappaB family acting
      specifically within myeloid cells to limit inflammatory responses in the lungs.

PMID- 19098125
TI  - Inhalation of urokinase-type plasminogen activator reduces airway remodeling in a
      murine asthma model.
AB  - The airway remodeling that occurs in asthma is characterized by an excess of
      extracellular matrix deposition in the submucosa, hyperplasia/hypertrophy of
      smooth muscle, goblet cell metaplasia, and accumulation of
      fibroblasts/myofibroblasts. The urokinase-type plasminogen activator
      (uPA)/plasmin system participates in pericellular proteolysis and is capable of
      directly degrading matrix components, activating latent proteinases, and
      activating growth factors. In a mouse ovalbumin (OVA) asthma model, we increased
      plasminogen activator activity in the lung by administering exogenous uPA or by
      using mice genetically deficient in the uPA inhibitor plasminogen activator
      inhibitor-1 (PAI-1) to assess the role of this system in asthma pathogenesis.
      After intraperitoneal OVA sensitization, mice inhaled OVA plus uPA (500 IU/mouse)
      or saline by ultrasonic nebulization for 3 wk. When studied 24 h after the final
      exposure, the groups with upregulated plasmin activity had significantly reduced
      subepithelial fibrosis within the airway walls and had decreased airway
      hyperresponsiveness (AHR) to methacholine. Morphometric analysis showed that
      subepithelial wall thickening of the bronchi (subepithelial area ratio) was also
      reduced, as were collagen and alpha-smooth muscle actin. Upregulation of plasmin
      activity also increased the level of hepatocyte growth factor activity in
      bronchoalveolar lavage fluid, whereas the release of transforming growth factor
      beta was decreased. The administration of uPA 1 wk after the last OVA inhalation
      also significantly reduced lung hydroxyproline content and AHR. These results
      show that enhancing uPA/plasmin activity lessens the airway remodeling in a
      murine asthma model.

PMID- 19098126
TI  - In vitro hypoxia impairs beta2-adrenergic receptor signaling in primary rat
      alveolar epithelial cells.
AB  - Hypoxia inhibits beta(2)-adrenergic receptor (beta(2)-AR) signaling in a variety
      of tissues, but effects in alveolar epithelium are unclear. We therefore examined
      the effect of 24 h of hypoxia on beta(2)-AR function in primary rat alveolar
      epithelial [alveolar type II (ATII)] cells. ATII cells were isolated, cultured to
      confluence, and incubated in normoxia or hypoxia (3% O(2)) for 24 h. Hypoxia
      decreased maximal terbutaline-stimulated cAMP production by 37%; potency of
      terbutaline was not affected. Reoxygenation (3 h) reversed this effect. Density
      of beta(2)-AR assessed by (-)-[(125)I]iodocyanopindolol binding was decreased in
      hypoxia (-22%). Hypoxia did not affect terbutaline binding affinity to beta(2)
      AR. Hypoxia decreased G(s) protein levels by 27%, whereas no change was observed
      in G(i1/2), G(i3), and Gbeta subunits. Forskolin-stimulated cAMP production was
      not inhibited by hypoxia. Pertussis toxin (PTX; 0.5 microg/ml, 2 h), an inhibitor
      of G(i/o) proteins, restored terbutaline-stimulated cAMP production of hypoxic
      ATII cells to normoxic control values. Cholera toxin (CTX)-stimulated G(s)
      protein activity did not change in hypoxia. Hypoxia increased the sensitivity of
      beta(2)-AR to desensitization. These results indicate that despite the decrease
      in G(s) protein level G(s) protein was still functional and that hypoxia impairs
      beta(2)-AR signaling due to an increased activity of G(i/o) proteins.

PMID- 19098128
TI  - Subcellular localization directs signaling specificity of the Cryptococcus
      neoformans Ras1 protein.
AB  - In the human fungal pathogen Cryptococcus neoformans, Ras signaling mediates
      sexual differentiation, morphogenesis, and pathogenesis. By studying Ras
      prenylation and palmitoylation in this organism, we have found that the
      subcellular localization of this protein dictates its downstream signaling
      specificity. Inhibiting C. neoformans Ras1 prenylation results in the defective
      general membrane targeting of this protein and the loss of all Ras function. In
      contrast, palmitoylation mediates localization of Ras1 to the plasma membrane and
      is required for normal morphogenesis and survival at high temperatures. However,
      palmitoylation and plasma membrane localization are not required for Ras
      dependent sexual differentiation. Likely as a result of its effect on
      thermotolerance, Ras1 palmitoylation is also required for the pathogenesis of C.
      neoformans. These data support an emerging paradigm of compartmentalized Ras
      signaling. However, our studies also demonstrate fundamental differences between
      the Ras pathways in different organisms that emphasize the functional flexibility
      of conserved signaling cascades.

PMID- 19098127
TI  - Cellular localization of mitochondria contributes to Kv channel-mediated
      regulation of cellular excitability in pulmonary but not mesenteric circulation.
AB  - Mitochondria are proposed to be a major oxygen sensor in hypoxic pulmonary
      vasoconstriction (HPV), a unique response of the pulmonary circulation to low
      oxygen tension. Mitochondrial factors including reactive oxygen species,
      cytochrome c, ATP, and magnesium are potent modulators of voltage-gated K(+)
      (K(v)) channels in the plasmalemmal membrane of pulmonary arterial (PA) smooth
      muscle cells (PASMCs). Mitochondria have also been found close to the
      plasmalemmal membrane in rabbit main PA smooth muscle sections. Therefore, we
      hypothesized that differences in mitochondria localization in rat PASMCs and
      systemic mesenteric arterial smooth muscle cells (MASMCs) may contribute to the
      divergent oxygen sensitivity in the two different circulations. Cellular
      localization of mitochondria was compared with immunofluorescent labeling, and
      differences in functional coupling between mitochondria and K(v) channels was
      evaluated with the patch-clamp technique and specific mitochondrial inhibitors
      antimycin A (acting at complex III of the mitochondrial electron transport chain)
      and oligomycin A (which inhibits the ATP synthase). It was found that
      mitochondria were located significantly closer to the plasmalemmal membrane in
      PASMCs compared with MASMCs. Consistent with these findings, the effects of the
      mitochondrial inhibitors on K(v) current (I(Kv)) were significantly more potent
      in PASMCs than in MASMCs. The cytoskeletal disruptor cytochalasin B (10 microM)
      also altered mitochondrial distribution in PASMCs and significantly attenuated
      the effect of antimycin A on the voltage-dependent parameters of I(Kv). These
      findings suggest a greater structural and functional coupling between
      mitochondria and K(v) channels specifically in PASMCs, which could contribute to
      the regulation of PA excitability in HPV.

PMID- 19098129
TI  - Global gene expression analysis during germination in the chytridiomycete
      Blastocladiella emersonii.
AB  - Blastocladiella emersonii is an aquatic fungus of the Chytridiomycete class.
      During germination, the zoospore, a motile nongrowing cell, goes through a
      cascade of morphological changes that culminates with its differentiation into
      the germling cell, capable of coenocytic vegetative growth. Transcriptome
      analyses of B. emersonii cells were carried out during germination induced under
      various environmental conditions. Microarray data analyzing 3,563 distinct B.
      emersonii genes revealed that 26% of them are differentially expressed during
      germination in nutrient medium at at least one of the time points investigated.
      Over 500 genes are upregulated during the time course of germination under those
      conditions, most being related to cell growth, including genes involved in
      protein biosynthesis, DNA transcription, energetic metabolism, carbohydrate and
      oligopeptide transport, and cell cycle control. On the other hand, several
      transcripts stored in the zoospores are downregulated during germination in
      nutrient medium, such as genes involved in signal transduction, amino acid
      transport, and chromosome organization. In addition, germination induced in the
      presence of nutrients was compared with that triggered either by adenine or
      potassium ions in inorganic salt solution. Several genes involved in cell growth,
      induced during germination in nutrient medium, do not show increased expression
      when B. emersonii zoospores germinate in inorganic solution, suggesting that
      nutrients exert a positive effect on gene transcription. The transcriptome data
      also revealed that most genes involved in cell signaling show the same expression
      pattern irrespective of the initial germination stimulus.

PMID- 19098132
TI  - A segment containing a G-box and an ACGT motif confers differential expression
      characteristics and responses to the Arabidopsis Cytc-2 gene, encoding an isoform
      of cytochrome c.
AB  - Sequences required for the expression of Cytc-2 (At4g10040), one of two
      cytochrome c genes from Arabidopsis thaliana, were characterized using plants
      transformed with deleted and mutagenized promoter fragments fused to gus. These
      studies indicated that a region containing a G-box and an ACGT motif is essential
      for expression. Mutation of the ACGT motif causes a complete loss of expression,
      while mutation of the G-box causes decreased expression in aerial parts and
      abolishes expression in roots and induction by environmental factors. Upstream
      located site II elements are required for maximal expression, mainly in
      reproductive tissues, and maximal induction by different factors. One-hybrid
      screenings allowed the identification of transcription factors from the bZIP and
      bHLH families that interact mainly with the G-box. Four of these factors were
      able to bind to the Cytc-2 promoter in vitro and in transactivation assays in
      Arabidopsis. Analysis of available microarray data indicated that the bZIP
      transcription factors share expression characteristics with the Cytc-2 gene,
      suggesting that they act as mediators of its response to tissue-specific,
      environmental, and metabolic conditions. Site II elements interact with a TCP
      family protein and may co-ordinate the expression of the Cytc-2 gene with that of
      other respiratory chain components. A model is proposed for the evolution of the
      Cytc-2 gene through the incorporation of a segment containing a G-box and an ACGT
      motif into an ancestral gene that contained site II elements. This may have
      reduced the importance of site II elements for basal expression and conferred new
      responses to environmental factors.

PMID- 19098131
TI  - RNA silencing is required for Arabidopsis defence against Verticillium wilt
      disease.
AB  - RNA silencing is a conserved mechanism in eukaryotes that plays an important role
      in various biological processes including regulation of gene expression. RNA
      silencing also plays a role in genome stability and protects plants against
      invading nucleic acids such as transgenes and viruses. Recently, RNA silencing
      has been found to play a role in defence against bacterial plant pathogens in
      Arabidopsis through modulating host defence responses. In this study, it is shown
      that gene silencing plays a role in plant defence against multicellular microbial
      pathogens; vascular fungi belonging to the Verticillium genus. Several components
      of RNA silencing pathways were tested, of which many were found to affect
      Verticillium defence. Remarkably, no altered defence towards other fungal
      pathogens that include Alternaria brassicicola, Botrytis cinerea, and
      Plectosphaerella cucumerina, but also the vascular pathogen Fusarium oxysporum,
      was recorded. Since the observed differences in Verticillium susceptibility
      cannot be explained by notable differences in root architecture, it is speculated
      that the gene silencing mechanisms affect regulation of Verticillium-specific
      defence responses.

PMID- 19098133
TI  - Accelerated (32)P-HPLC for bulky DNA adducts.
AB  - Many compounds can react with DNA forming covalent modifications, so-called DNA
      adducts, which can influence crucial biological processes. DNA adducts from
      various DNA-damaging agents can act both as biomarkers and as a measurement of
      the actual damage of the genome. Therefore, they are of value in determining
      exposed or sensitive individuals or populations and in identifying agents that
      can induce DNA damage. A common method to measure DNA adducts is through DNA
      hydrolysis, adduct enrichment, (32)P-post-labelling and chromatographic
      separation. High-performance liquid chromatography (HPLC) with online
      radioactivity detection, the (32)P-HPLC (direct injection of the (32)P-labelled
      mixture into the HPLC with online (32)P-detection) method, gives both high
      sensitivity and good resolution of complex mixtures of DNA adducts. One
      limitation with this method is the capacity when dealing with large numbers of
      samples. The aim of this study was therefore to increase the analytical capacity
      by reducing analysis time of the (32)P-HPLC method. A change of HPLC columns to
      low backpressure columns and adaptation of elution conditions enabled a reduction
      in time per analysis from 100 to 20 min. This did not affect sensitivity but
      lowered chromatographic resolution, although bulky DNA adducts were still well
      resolved from other DNA components. This is useful when the total amount of DNA
      adducts is the primary interest. When high resolution is required, this can be
      achieved by gradient modifications, which increase the time required per analysis
      to 30 min. The accelerated (32)P-HPLC increases the capacity in number of samples
      3- to 5-fold, depending on resolution requirements, without any negative effect
      on sensitivity in both in vitro and in vivo samples.

PMID- 19098134
TI  - Common ground on surgical abortion?--engaging Peter Singer on the moral status of
      potential persons.
AB  - The debate over surgical abortion is certainly one of the most divisive in
      ethical discourse and for many it seems interminable. However, this paper argues
      that a primary reason for this is confusion with regard to what issues are
      actually under dispute. When looking at an entrenched and articulate figure on
      one side of the debate, Peter Singer, and comparing his views with those of his
      opponents, one finds that the disputed issue is actually quite a narrow one: the
      moral status of potential persons. Finding this common ground clears the
      conceptual space for a fruitful argument: the thesis of which is that most,
      including Singer, who argue that potential persons do not have full personal
      moral status fail to make the necessary distinction between natural potential
      (which confers moral status) and practical potential (which admittedly does not).

PMID- 19098135
TI  - Methodological issues related to longitudinal epidemiological assessment of
      developmental trajectories in children.
AB  - This supplement presents some of the methodological issues that arose during the
      early phases of protocol development for the National Children's Study (NCS), a
      probability sample of 100,000 children that will be followed prospectively from
      pregnancy through 21 years of age, and to share some of the challenges and
      solutions that were discussed. These papers on motor, social/emotional,
      psychiatric and neurocognitive/behavioural development do not define the protocol
      of the NCS, but reflect methodology related to the design of research and
      assessment of developmental trajectories in children that may be useful to other
      epidemiologists planning similar longitudinal studies.

PMID- 19098136
TI  - Assessment of neuropsychological trajectories in longitudinal population-based
      studies of children.
AB  - This paper provides a strategy for the assessment of brain function in
      longitudinal cohort studies of children. The proposed strategy invokes both
      domain-specific and omnibus intelligence test approaches. In order to minimise
      testing burden and practice effects, the cohort is divided into four groups with
      one-quarter tested at 6-monthly intervals in the 0-2-year age range (at ages 6
      months, 1.0, 1.5 and 2.0 years) and at annual intervals from ages 3-20 (one
      quarter of the children at age 3, another at age 4, etc). This strategy allows
      investigation of cognitive development and of the relationship between
      environmental influences and development at each age. It also allows introduction
      of new domains of function when age-appropriate. As far as possible, tests are
      used that will provide a rich source of both longitudinal and cross-sectional
      data. The testing strategy allows the introduction of novel tests and new domains
      as well as piloting of tests when the test burden is relatively light. In
      addition to the recommended tests for each age and domain, alternative tests are
      described. Assessment methodology and knowledge about child cognitive development
      will change over the next 20 years, and strategies are suggested for altering the
      proposed test schedule as appropriate.

PMID- 19098137
TI  - Proposed motor development assessment protocol for epidemiological studies in
      children.
AB  - This paper proposes an approach to the implementation of a large-scale
      epidemiological study of child development. It addresses specifically how one
      might assess gross motor development longitudinally in a large population-based
      study of children, and recommends a three-phase process. Phase I, applied at key
      ages with the entire population, involves the use of parent-report screening
      tools that ask about specific age-appropriate motor skills, as well as any
      parental concerns about "quantity" or "quality" of their child's motor function
      and about any loss of motor function. In phase II, children who "fail" the
      screening phase (at any stage) are evaluated with specified developmental motor
      assessments. Those who "pass" revert to the screening stream, while those who
      "fail" continue to phase III. In this third component of the study, children are
      referred to experts in child development formally engaged in the study (including
      developmental paediatricians, paediatric neurologists and developmental
      therapists). These experts will use protocol-based evaluations to ascertain
      whether a child has a problem in development, what the problem might be from a
      diagnostic perspective, how "severe" the problem is, and what management services
      are or should be provided. It is argued that this is an efficient approach to the
      study of a population that would enable investigators to detect specific
      relatively common developmental motor disorders (in particular, cerebral palsy
      and developmental coordination disorder).

PMID- 19098138
TI  - Assessing social-emotional development in children from a longitudinal
      perspective.
AB  - This paper provides an overview of methodological challenges related to the
      epidemiological assessment of social-emotional development in children. Because
      population-based studies involve large cohorts and are usually multicentre in
      structure, they have cost, participant burden and other specific issues that
      affect the feasibility of the types of measures that can be administered. Despite
      these challenges, accurate in-depth assessment of social-emotional functioning is
      crucial, based on its importance to child outcomes like mental health, academic
      performance, delinquency and substance abuse. Five dimensions of social-emotional
      development in children are defined: (1) social competence; (2) attachment; (3)
      emotional competence; (4) self-perceived competence; and (5)
      temperament/personality. Their measurement in a longitudinal study and associated
      challenges are discussed. Means of making valid, reliable assessments while at
      the same time minimising the multiple challenges posed in the epidemiological
      assessment of social-emotional development in children are reviewed.

PMID- 19098130
TI  - Gene expression profiling in the human pathogenic dermatophyte Trichophyton
      rubrum during growth on proteins.
AB  - Dermatophytes are highly specialized filamentous fungi which cause the majority
      of superficial mycoses in humans and animals. The high secreted proteolytic
      activity of these microorganisms during growth on proteins is assumed to be
      linked to their particular ability to exclusively infect keratinized host
      structures such as the skin stratum corneum, hair, and nails. Individual secreted
      dermatophyte proteases were recently described and linked with the in vitro
      digestion of keratin. However, the overall adaptation and transcriptional
      response of dermatophytes during protein degradation are largely unknown. To
      address this question, we constructed a cDNA microarray for the human pathogenic
      dermatophyte Trichophyton rubrum that was based on transcripts of the fungus
      grown on proteins. Profiles of gene expression during the growth of T. rubrum on
      soy and keratin protein displayed the activation of a large set of genes that
      encode secreted endo- and exoproteases. In addition, other specifically induced
      factors potentially implicated in protein utilization were identified, including
      heat shock proteins, transporters, metabolic enzymes, transcription factors, and
      hypothetical proteins with unknown functions. Of particular interest is the
      strong upregulation of key enzymes of the glyoxylate cycle in T. rubrum during
      growth on soy and keratin, namely, isocitrate lyase and malate synthase. This
      broad-scale transcriptional analysis of dermatophytes during growth on proteins
      reveals new putative pathogenicity-related host adaptation mechanisms of these
      human pathogenic fungi.

PMID- 19098139
TI  - Approaches to psychiatric assessment in epidemiological studies of children.
AB  - An assessment protocol for the longitudinal measurement of developmental
      psychopathology in a population-based study of children and adolescents is
      proposed. The protocol is designed for use in a large cohort of up to 100,000
      individuals followed from early gestation to 21 years of age. Although the
      protocol was constrained by specified methodological parameters, the
      recommendations may apply to other psychiatric epidemiological research designs.
      The issues and challenges inherent with psychiatric assessments in longitudinal
      epidemiological studies of children and adolescents are discussed.

PMID- 19098140
TI  - Effect of the microenvironment and embryo density on developmental
      characteristics and gene expression profile of bovine preimplantative embryos
      cultured in vitro.
AB  - The Well of the Well (WOW) system has been developed to culture embryos in small
      groups or to track the development of single embryos. In the present study, we
      aimed to examine the effects of the microenvironment provided by the WOW system
      and embryo density on developmental rates, embryo quality and preimplantative
      gene expression profile of the resulting embryos. Embryos cultured in a group of
      16 reached the blastocyst stage at a significantly lower level than zygotes
      cultured in a group of 50 (22.2 vs 30.3%), whereas zygotes cultured in WOW were
      able to compensate against low embryo densities, reaching a blastocyst rate as
      high as embryos cultured in a group of 50 (31.3 vs 30.3%). Moreover, embryos
      derived from WOW culture did not differ in terms of differential cell counts and
      apoptotic cell index compared with controls. The gene expression analysis
      revealed 62 transcripts to be upregulated and 33 transcripts to be downregulated
      by WOW culture. Comparing the in vivo derived blastocysts with the blastocysts
      derived from WOW culture, and group culture, expression of ATP5A1, PLAC8 and KRT8
      was more similar to the embryos derived from WOW culture, whereas expression of
      S100A10 and ZP3 genes was more similar to blastocysts cultured in a group. In
      conclusion, microenvironment as well as embryo density significantly affected
      developmental rates. While subsequent blastocysts did not differ in terms of
      differential cell counts and apoptotic cell index, significant differences were
      observed in terms of the relative abundance of transcripts in the resulting
      embryos.

PMID- 19098141
TI  - Sox9-dependent expression of Gstm6 in Sertoli cells during testis development in
      mice.
AB  - Glutathione S-transferases (GSTs) are an important family of multifunctional
      enzymes that play a role in the protection of tissues by the detoxification of
      hazardous and carcinogenic compounds. We found previously that Gstm6 is
      upregulated in the somatic cells of male mouse fetal gonads relative to female
      gonads. In this study, we describe the spatial and temporal expression pattern of
      Gstm6 during mouse development. We show that Gstm6 is predominantly expressed in
      the reproductive system, at significantly higher levels in XY gonads compared
      with XX gonads from 11.5 dpc onwards, and remains expressed in the testes in
      adult mice. Its expression is associated with the Sertoli cell lineage, and is
      dependent on the expression of the male sex-determining gene Sox9. Our data
      suggest that Gstm6 plays a male-specific role in gonad development or function,
      possibly by modulating the exposure of somatic tissue and/or germ cells to
      endogenous or exogenous toxicants.

PMID- 19098143
TI  - Science of the conscious mind.
AB  - Human beings have direct access to their own mental states, but can only
      indirectly observe cosmic radiation and enzyme kinetics. Why then can we measure
      the temperature of far away galaxies and the activation constant of kinases to
      the third digit, yet we only gauge our happiness on a scale from 1 to 7? Here we
      propose a radical research paradigm shift to embrace the subjective conscious
      mind into the realm of objective empirical science. Key steps are the axiomatic
      acceptance of first-person experiences as scientific observables; the definition
      of a quantitative, reliable metric system based on natural language; and the
      careful distinction of subjective mental states (e.g., interpretation and intent)
      from physically measurable sensory and motor behaviors (input and output). Using
      this approach, we propose a series of reproducible experiments that may help
      define a still largely unexplored branch of science. We speculate that the
      development of this new discipline will be initially parallel to, and eventually
      converging with, neurobiology and physics.

PMID- 19098144
TI  - Consciousness as integrated information: a provisional manifesto.
AB  - The integrated information theory (IIT) starts from phenomenology and makes use
      of thought experiments to claim that consciousness is integrated information.
      Specifically: (i) the quantity of consciousness corresponds to the amount of
      integrated information generated by a complex of elements; (ii) the quality of
      experience is specified by the set of informational relationships generated
      within that complex. Integrated information (Phi) is defined as the amount of
      information generated by a complex of elements, above and beyond the information
      generated by its parts. Qualia space (Q) is a space where each axis represents a
      possible state of the complex, each point is a probability distribution of its
      states, and arrows between points represent the informational relationships among
      its elements generated by causal mechanisms (connections). Together, the set of
      informational relationships within a complex constitute a shape in Q that
      completely and univocally specifies a particular experience. Several observations
      concerning the neural substrate of consciousness fall naturally into place within
      the IIT framework. Among them are the association of consciousness with certain
      neural systems rather than with others; the fact that neural processes underlying
      consciousness can influence or be influenced by neural processes that remain
      unconscious; the reduction of consciousness during dreamless sleep and
      generalized seizures; and the distinct role of different cortical architectures
      in affecting the quality of experience. Equating consciousness with integrated
      information carries several implications for our view of nature.

PMID- 19098145
TI  - Importance of time and place: patterns in abundance of Symbiodinium clades A and
      B in the tropical sea anemone Condylactis gigantea.
AB  - The capacity of some corals and other cnidarians to form symbioses with multiple
      algae (Symbiodinium) is a candidate route by which these symbioses tolerate
      variable environmental conditions. On Bermuda, the coral reef dwelling anemone
      Condylactis gigantea bears Symbiodinium of clades A and B. At thermally variable
      inshore and nearshore sites, clade A predominates (as sole symbiont or in mixed
      infection with clade B), whereas animals at offshore sites with more uniform
      temperatures bear only clade B or mixed infections. Individual animals at one
      nearshore site monitored over a year by sampling tentacles showed increased
      prevalence of clade A in March-November, when sea waters were warm (average 26
      degrees C), and increased clade B in November-March when cool waters prevailed
      (average 18.5 degrees C). In laboratory analyses of excised tentacles, the
      symbiosis with clade B, but not clade A, bleached at elevated temperature (32
      degrees C), suggesting that thermal tolerance may contribute to the higher
      prevalence of clade A at inshore/nearshore sites and in the summer. The temporal
      changes in the algal complement were not accompanied by bleaching, and
      Symbiodinium density fluctuated in hosts with stable Symbiodinium composition but
      not in hosts with variable composition. This suggests that changes in the
      relative abundance of Symbiodinium clades do not require bleaching and may even
      protect the symbiosis from large fluctuations in algal density.

PMID- 19098146
TI  - Heat stress in the intertidal: comparing survival and growth of an invasive and
      native mussel under a variety of thermal conditions.
AB  - In the rocky intertidal, organisms frequently experience a wide range of daily
      body temperatures depending on the stage of the tide and the time of day. In the
      intertidal, the thermal adaption of a species and its ability to invade a new
      region may be closely linked. In this research, the physiological effects of
      thermal stress in both low tide and high tide conditions are compared between
      Mytilus galloprovincialis, a worldwide mussel invader, and M. trossulus, a
      sibling species. In a seawater tank, mussels were exposed to one of three aerial
      temperature treatments (20, 25, 30 degrees C) in a cycle with one of two water
      temperatures (18, 12 degrees C). In 18 degrees C water, there was no effect of
      the aerial treatments on growth or survival in either species. In contrast, in 12
      degrees C water, aerial exposure affected the survival and growth of both
      species. Growth and survival rates of M. galloprovincialis were higher in all
      conditions than the rates of M. trossulus, especially in the 18 degrees C water
      experiments and in the aerial exposure treatments of the winter 12 degrees C
      water experiment. M. galloprovincialis appears to be warm-adapted with regard to
      both low tide and high tide thermal stress. These results when paired with
      previous research suggest that as climates shift due to global warming, the
      temperatures favorable to M. galloprovincialis will become more common.

PMID- 19098147
TI  - Multiple mating, sperm storage, and mating preference in Aplysia californica.
AB  - Aplysia californica, a simultaneous hermaphrodite, has the ability to store and
      digest allosperm and frequently mates with multiple partners. Using controlled
      matings and behavioral observations, we characterized the mating behavior of
      multiply-mated A. californica. Regardless of their initial mating role, all
      animals mated a second time. Individuals acting as the initial sperm donor showed
      no preference for second mating role when paired with a "virgin" partner.
      However, individuals acting as the initial sperm recipient showed a highly
      significant preference for acting as the sperm donor in subsequent matings, when
      paired with a "virgin" partner. This preference disappeared when the initial
      sperm recipient spawned a fertilized egg mass prior to the second mating bout. On
      average, singly mated animals laid 2.85 +/- 0.39 (mean +/- SE, n = 13) egg masses
      before accepting sperm from a second donor. These results support the notion that
      depletion of stored allosperm plays a crucial role in the resolution of sexual
      conflict and the mating decisions of A. californica.

PMID- 19098148
TI  - Upside-down gliding of Lymnaea.
AB  - The pond snail Lymnaea stagnalis can often be observed moving upside down on its
      back just below the surface of the water. We have termed this form of movement
      "upside-down gliding." To elucidate the mechanism of this locomotion, we
      performed a series of experiments involving behavioral analyses and microscopic
      observations. These experiments were designed (1) to measure the speed of this
      locomotion; (2) to determine whether the mucus secreted from the foot of Lymnaea
      repels water, thereby allowing the snail to exploit the surface tension of the
      water for upside-down gliding; and (3) to observe the beating of foot cilia in
      this behavior. The beating of these cilia is thought to be the primary driving
      force for upside-down gliding. Our results demonstrate that upside-down gliding
      is an efficient active process involving the secretion of mucus that floats up to
      the water surface to serve as a substrate upon which cilia beat to cause
      locomotion at the underside of the water surface.

PMID- 19098149
TI  - Development of the 5-HT-like immunoreactive pedal plexus in the pond snail
      Lymnaea stagnalis appressa.
AB  - In many gastropods, a serotonin-like immunoreactive axon plexus lies over ciliary
      cells on the pedal sole. The origin and function of axons in this plexus is
      uncertain. By using serotonin antibodies in the direct-developing embryo of the
      pond snail, the axons that initially form this plexus were traced from seven
      large neurons in each pedal ganglion. Soon after metamorphosis begins, the first
      immunoreactive pedal ganglion neuron sends multiple branched neurites to lie
      directly over pedal sole ciliary cells. By 70% of the 11 days required for
      hatching, axons from the seven neuron pairs form a plexus over ciliary cells in
      the whole sole. The axon from each of the seven neurons is guided to a specific
      area of the pedal plexus where ciliary cells are developing. Axons from two pairs
      of these neurons, which form the pedal plexus in the posterior part of the foot,
      are in the unpaired nerve that comes from the pedal ganglia ventral commissure.
      It is likely that these two developing neuron pairs are homologs of the two
      neuron pairs in Lymnaea stagnalis that have axons in this ventral commissure
      nerve. Identification of these neurons and the other five neuron pairs with axons
      in the pedal plexus will provide a basis for future studies of the relation
      between the plexus and pedal ciliary locomotion.

PMID- 19098150
TI  - Flow forces on seaweeds: field evidence for roles of wave impingement and
      organism inertia.
AB  - Hydrodynamic forces dislodge and kill large numbers of organisms in intertidal
      and subtidal habitats along rocky shores. Although this feature of wave-driven
      water motion is well recognized, the mechanics of force imposition on compliant
      organisms is incompletely understood. Here we undertake a field examination of
      two processes that are thought to impose many of the more dangerous forces that
      act on flexible benthic seaweeds: impingement of breaking waves directly on
      emergent organisms, and inertial effects tied to the rapid deceleration of mass
      that occurs when a passively moving but attached organism abruptly reaches the
      extent of its range of motion. We focus on two common and important seaweed
      species: one intertidal kelp (Egregia menziesii) and one subtidal kelp
      (Macrocystis pyrifera). Results support the concept that wave impingement and
      inertial effects produce intermittent force transients whose magnitudes commonly
      exceed values readily attributable to drag. Peak force transients are elevated by
      as much as a factor of 3 relative to drag in both small and large individuals,
      consistent with smaller seaweeds being more susceptible to brief impingement
      forces, and larger seaweeds being more vulnerable to inertial forces. Because
      both wave impingement and inertial effects vary with the size of an organism,
      they may have the potential to influence the demographics of physical disturbance
      in an array of flexible species.

PMID- 19098151
TI  - Intra-oral flow patterns and speeds in a suspension-feeding fish with gill rakers
      removed versus intact.
AB  - Oreochromis aureus, a species of tilapia, is a suspension-feeding fish that
      employs a pumping action to bring water into its mouth for filtering.To address
      questions about water flow inside the mouth, we used a microthermistor flow probe
      to determine the speed of intra-oral flow during suspension feeding in this
      species before and after surgical removal of gill rakers. Synchronization with
      high-speed external videotapes of the fish and high-speed video endoscopy inside
      the oropharyngeal cavity allowed the first correlation of oral actions with intra
      oral flow patterns and speeds during feeding. This analysis established the
      occurrence of a brief reversal of flow ( approximately 80-ms duration) from
      posterior to anterior in the oropharyngeal cavity prior to every feeding pump
      (250-500-ms duration). In industrial crossflow filtration, oscillating or
      pulsatile flow increases filtration performance by enhancing the back-migration
      of particles from the region near the filter surface to the bulk flow region,
      thus reducing particle accumulation that can clog the filter. In endoscopic
      videotapes, these pre-pump reversals, as well as post-pump reversals (
      approximately 500-ms duration), were observed to lift mucus and particles from
      the branchial arches for subsequent transport toward the esophagus. Intra-oral
      flow speeds were reduced markedly after removal of the gill rakers. We
      hypothesize that the decrease in crossflow speed during feeding pumps following
      the removal of gill rakers and mucus could be due to increased loss of water
      between the anterior branchial arches.

PMID- 19098153
TI  - Predictors of hip internal rotation during running: an evaluation of hip strength
      and femoral structure in women with and without patellofemoral pain.
AB  - BACKGROUND: Recent studies have suggested that excessive hip internal rotation
      during dynamic tasks may be associated with patellofemoral pain. Although
      diminished hip-muscle strength and altered femoral morphologic characteristics
      have been implicated in abnormal hip rotation in persons with patellofemoral
      pain, no study has confirmed this hypothesis. HYPOTHESIS: Women with
      patellofemoral pain would demonstrate increased average hip internal rotation,
      decreased hip-muscle performance, and abnormal femoral shape compared with
      controls. Furthermore, measures of hip strength and femoral shape are predictive
      of average hip internal rotation during running. STUDY DESIGN: Cross-sectional
      study; Level of evidence, 3. METHODS: Nineteen women with patellofemoral pain and
      19 pain-free controls participated. Lower extremity kinematics during running,
      hip-muscle performance, and femoral morphologic characteristics on magnetic
      resonance imaging were quantified. Independent t tests were used to assess group
      differences. Stepwise linear regression was used to determine whether measures of
      strength and/or structure were predictive of average hip internal rotation during
      running. RESULTS: Participants with patellofemoral pain demonstrated
      significantly greater average hip internal rotation (8.2 degrees +/- 6.6 degrees
      vs 0.3 degrees +/- 3.6 degrees ; P < .001), reduced hip-muscle strength in 8 of
      10 hip strength measurements, and greater femoral inclination (132.8 degrees +/-
      5.2 degrees vs 128.4 degrees +/- 5.0 degrees ; P = .011) compared with controls.
      Stepwise regression revealed that isotonic hip extension endurance was the only
      predictor of average hip internal rotation (r = -.451; P = .004). CONCLUSION:
      Abnormal hip kinematics in women with patellofemoral pain appears to be the
      result of diminished hip-muscle performance as opposed to altered femoral
      structure. The results suggest that assessment of hip-muscle performance should
      be considered in the evaluation and treatment of patellofemoral joint
      dysfunction.

PMID- 19098154
TI  - Medial collateral ligament injuries and subsequent load on the anterior cruciate
      ligament: a biomechanical evaluation in a cadaveric model.
AB  - BACKGROUND: Numerous studies have documented the effect of complete medial
      collateral ligament injury on anterior cruciate ligament loads; few have
      addressed how partial medial collateral ligament disruption affects knee
      kinematics. PURPOSE: To determine knee kinematics and subsequent change in
      anterior cruciate ligament load in a partial and complete medial collateral
      ligament injury model. STUDY DESIGN: Controlled laboratory study. METHODS: Ten
      human cadaveric knees were sequentially tested by a robot with the medial
      collateral ligament intact, in a partial injury model, and in a complete injury
      model with a universal force-moment sensor measuring system. Tibial translation,
      rotation, and anterior cruciate ligament load were measured under 3 conditions:
      anterior load (125 N), valgus load (10 N x m), and internal-external rotation
      torque (4 N x m; all at 0 degrees and 30 degrees of flexion). RESULTS: Anterior
      and posterior translation did not statistically increase with a partial or
      complete medial collateral ligament injury at 0 degrees and 30 degrees of
      flexion. In response to a 125 N anterior load, at 0 degrees , the anterior
      cruciate ligament load increased 8.7% (from 99.5 to 108.2 N; P = .006) in the
      partial injury and 18.3% (117.7 N; P < .001) in the complete injury; at 30
      degrees , anterior cruciate ligament load was increased 12.3% (from 101.7 to
      114.2 N; P = .001) in the partial injury and 20.6% (122.7 N; P < .001) in the
      complete injury. In response to valgus torque (10 N x m) at 30 degrees , anterior
      cruciate ligament load was increased 55.3% (30.4 to 47.2 N; P = .044) in the
      partial injury model and 185% (86.8 N; P = .001) in the complete injury model. In
      response to internal rotation torque (4 N.m) at 30 degrees , anterior cruciate
      ligament load was increased 29.3% (27.6 to 35.7 N; P = .001) in the partial
      injury model and 65.2% (45.6 N; P < .001) in the complete injury model. The
      amount of internal rotation at 30 degrees of flexion was significantly increased
      in the complete injury model (22.8 degrees ) versus the intact state (19.5
      degrees ; P < .001). CONCLUSION: Partial and complete medial collateral ligament
      tears significantly increased the load on the anterior cruciate ligament. In a
      partial tear, the resultant load on the anterior cruciate ligament was increased
      at 30 degrees of flexion and with valgus load and internal rotation torque.
      CLINICAL RELEVANCE: Patients may need to be protected from valgus and internal
      rotation forces after anterior cruciate ligament reconstruction in the setting of
      a concomitant partial medial collateral ligament tear. This information may help
      clinicians understand the importance of partial injuries of the medial collateral
      ligament with a combined anterior cruciate ligament injury complex.

PMID- 19098155
TI  - Biomarkers for lung cancer screening: interpretation and implications of an early
      negative advanced validation study.

PMID- 19098156
TI  - Once-weekly treatment of tuberculosis with the diarylquinoline R207910: a real
      possibility.

PMID- 19098157
TI  - The INSPIRE trial results: are they truly breathtaking?

PMID- 19098158
TI  - Outcomes in children with obstructive sleep apnea.

PMID- 19098159
TI  - Does current drug resistance surveillance provide useful information in
      tuberculosis?

PMID- 19098160
TI  - Identification and characterization of proximal promoter polymorphisms in the
      human concentrative nucleoside transporter 2 (SLC28A2).
AB  - The human concentrative nucleoside transporter 2 (CNT2) plays an important role
      in the absorption, disposition, and biological effects of endogenous nucleosides
      and nucleoside analog drugs. We identified genetic variation in the basal
      promoter region of CNT2 and characterized the function of the variants. We
      screened DNA from an ethnically diverse population and identified five basal
      promoter variants in CNT2. Three major haplotypes in the CNT2 basal promoter
      region were identified and were found at different allele frequencies in various
      ethnic groups. The common promoter variants and haplotypes were constructed and
      characterized for their promoter activity using luciferase reporter assays. One
      polymorphic variant, rs2413775 (-146T>A), with an allele frequency >20% in all
      populations, showed a gain of function in luciferase activity. Furthermore, in
      vivo mouse promoter assays of these nucleotide variants using the hydrodynamic
      tail vein injection, leading to their expression in the liver, demonstrated
      similar results. Transcription factor binding site (TFBS) analysis indicated this
      variant alters a hepatic nuclear factor (HNF) 1 TFBS. Electrophoretic mobility
      shift assay demonstrated stronger binding of HNF1alpha and weaker binding of
      HNF1beta to the -146T and -146A regions, whereas the single nucleotide
      polymorphism (SNP), -146A, exhibited enhanced binding to both HNF1alpha and
      HNF1beta, consistent with its greater activity in reporter assays. The data
      collectively suggest that the common variant, -146T>A, in the proximal promoter
      of CNT2 may result in an enhanced transcription rate of the gene and, thus,
      expression levels of CNT2. This SNP may play a role in variation in the
      pharmacokinetics and pharmacological effects of nucleoside analogs.

PMID- 19098161
TI  - Inhaled insulin is associated with prolonged enhancement of glucose disposal in
      muscle and liver in the canine.
AB  - Diabetic patients treated with inhaled insulin exhibit reduced fasting plasma
      glucose levels. In dogs, insulin action in muscle is enhanced for as long as 3 h
      after insulin inhalation. This study was designed to determine whether this
      effect lasts for a prolonged duration such that it could explain the effect
      observed in diabetic patients. Human insulin was administered via inhalation
      (Exubera; n = 9) or infusion (Humulin R; n = 9) in dogs using an infusion
      algorithm that yielded matched plasma insulin kinetics between the two groups.
      Somatostatin was infused to prevent insulin secretion, and glucagon was infused
      to replace basal plasma levels of the hormone. Glucose was infused into the
      portal vein at 4 mg/kg/min and into a peripheral vein to maintain the arterial
      plasma glucose level at 160 mg/dl. Arterial and hepatic sinusoidal insulin and
      glucose levels were virtually identical in the two groups. Notwithstanding,
      glucose utilization was greater when insulin was administered by inhalation. At
      its peak, the peripheral glucose infusion rate was 4 mg/kg/min greater in the
      inhalation group, and a 50% difference between groups persisted over 8 h.
      Inhalation of insulin caused a greater increase in nonhepatic glucose uptake in
      the first 3 h after inhalation; thereafter, net hepatic glucose uptake was
      greater. Inhalation of insulin was associated with greater than expected (based
      on insulin levels) glucose disposal. This may explain the reduced fasting glucose
      concentrations observed in humans after administration of certain inhaled insulin
      formulations compared with subcutaneous insulin.

PMID- 19098162
TI  - Antipsychotic-like effect of retigabine [N-(2-Amino-4-(fluorobenzylamino)
      phenyl)carbamic acid ester], a KCNQ potassium channel opener, via modulation of
      mesolimbic dopaminergic neurotransmission.
AB  - Dopaminergic (DAergic) neurons in the ventral tegmental area express both KCNQ2
      and KCNQ4 channels, which opening is expected to decrease neuronal excitability
      via neuronal hyper-polarization. Because psychotic symptoms are believed to be
      associated with an increased excitability of dopamine (DA) cells in the
      mesencephalon, KCNQ channels might represent a new potential target for the
      treatment of psychosis. The aim of our study was to investigate the antipsychotic
      like potential of KCNQ channel opening via modulation of neuronal activity within
      the mesolimbic DAergic system. We report that retigabine [N-(2-amino-4
      (fluorobenzylamino)-phenyl)carbamic acid ester], a KCNQ opener, dose-dependently
      reduced basal DA firing rate and more potently suppressed burst firing activity
      in the ventral tegmental area, whereas XE-991 [10,10-bis(pyridinylmethyl)-9(10H)
      anthracenone], a selective KCNQ blocker, induced opposite effects. In addition,
      retigabine prevented d-amphetamine-induced DA efflux in the nucleus accumbens and
      d-amphetamine-induced locomotor hyperactivity. In contrast, XE-991 potentiated
      both the locomotor hyperactivity and DA efflux evoked by d-amphetamine. These
      data strongly suggest that the activation of KCNQ channels attenuates DAergic
      neurotransmission in the mesolimbic system, particularly in conditions of
      excessive DAergic activity. In a model predictive of antipsychotic activity, the
      conditioned avoidance response paradigm, retigabine was found to inhibit
      avoidance responses, an effect blocked by coadministration of XE-991.
      Furthermore, retigabine was found to significantly inhibit the hyperlocomotor
      response to a phencyclidine (PCP) challenge in PCP-sensitized animals, considered
      as a disease model for schizophrenia. Taken together, our studies provide
      evidence that KCNQ channel openers represent a potential new class of
      antipsychotics.

PMID- 19098163
TI  - Protein kinase Cbeta is a critical regulator of dopamine transporter trafficking
      and regulates the behavioral response to amphetamine in mice.
AB  - The dopamine transporter (DAT) is a key mediator of dopaminergic
      neurotransmission and a major target for amphetamine. We found previously that
      protein kinase C (PKC) beta regulates amphetamine-mediated dopamine efflux. Here,
      using PKCbeta wild-type (WT) and knockout (KO) mice, we report a novel role for
      PKCbeta in amphetamine-induced regulation of DAT trafficking and activity.
      PKCbeta KO mice have less striatal surface DAT, [3H]dopamine uptake, and
      amphetamine-stimulated dopamine efflux, yet higher novelty-induced locomotor
      activity than WT mice. Although a short exposure (< or =90 s) to amphetamine
      rapidly increases striatal surface DAT and [3H]dopamine uptake in WT mice, this
      treatment decreases surface DAT and [3H]dopamine uptake in KO mice. Increases in
      surface DAT and [3H]dopamine uptake are not evident in KO mice until a longer
      exposure (60 min) to amphetamine, by which time WT mice exhibit decreased surface
      DAT and dopamine uptake. The slowness of amphetamine-induced striatal DAT
      trafficking in PKCbeta KO mice was mimicked by the use of a specific PKCbeta
      inhibitor, LY379196, in WT mice. Furthermore, PKCbeta KO mice exhibit reduced
      locomotor responsiveness to amphetamine compared with WT, which could be
      explained by reduced surface DAT and delayed amphetamine-induced DAT trafficking
      in KO mice. Our results indicate that PKCbeta is crucial for proper trafficking
      of DAT to the surface and for functioning of DAT and amphetamine signaling,
      providing new insight into the role of PKCbeta as an important regulator of
      dopaminergic homeostasis.

PMID- 19098164
TI  - Discriminative stimulus effects of 1-(2,5-dimethoxy-4-methylphenyl)-2
      aminopropane in rhesus monkeys: antagonism and apparent pA2 analyses.
AB  - Discriminative stimulus effects of the serotonin (5-HT) receptor agonist 1-(2,5
      dimethoxy-4-methylphenyl)-2-aminopropane (DOM) have been studied in rats and,
      more recently, in rhesus monkeys. This study examined DOM, 2,5-dimethoxy-4-(n)
      propylthiophenethylamine (2C-T-7), and dipropyltryptamine hydrochloride (DPT)
      alone and in combination with three antagonists, MDL100907 [(+/-)2,3
      dimethoxyphenyl-1-[2-(4-piperidine)-methanol]], ketanserin [3-[2-[4-(4
      fluorobenzoyl)piperidin-1-yl]ethyl]-1H-quinazoline-2,4-dione], and ritanserin [6
      [2-[4-[bis(4-fluorophenyl)methylidene]piperidin-1-yl]ethyl]-7-methyl
      [1,3]thiazolo[2,3-b]pyrimidin-5-one], to identify the 5-HT receptor subtype(s)
      that mediates the discriminative stimulus effects of these 5-HT receptor
      agonists. Four adult rhesus monkeys discriminated between 0.32 mg/kg s.c. DOM and
      vehicle while responding under a fixed ratio 5 schedule of stimulus shock
      termination. DOM, 2C-T-7, and DPT dose-dependently increased responding on the
      DOM-associated lever. MDL100907 (0.001-0.01 mg/kg), ketanserin (0.01-0.1 mg/kg),
      and ritanserin (0.01-0.1 mg/kg) each shifted the dose-response curves of DOM, 2C
      T-7, and DPT rightward in a parallel manner. Schild analysis of each drug
      combination was consistent with a simple, competitive, and reversible
      interaction. Similar apparent affinity (pA(2)) values were obtained for MDL100907
      in combination with DOM (8.61), 2C-T-7 (8.58), or DPT (8.50), for ketanserin with
      DOM (7.67), 2C-T-7 (7.75), or DPT (7.71), and for ritanserin with DOM (7.65), 2C
      T-7 (7.75), or DPT (7.65). Potency of antagonists in this study was correlated
      with binding affinity at 5-HT(2A) receptors and not at 5-HT(2C) or alpha(1)
      adrenergic receptors. This study used Schild analysis to examine receptor
      mechanisms mediating the discriminative stimulus effects of hallucinogenic drugs
      acting at 5-HT receptors; results provide quantitative evidence for the
      predominant, if not exclusive, role of 5-HT(2A) receptors in the discriminative
      stimulus effects of DOM, 2C-T-7, and DPT in rhesus monkeys.

PMID- 19098165
TI  - The novel neuropeptide Y Y5 receptor antagonist Lu AA33810 [N-[[trans-4-[(4,5
      dihydro[1]benzothiepino[5,4-d]thiazol-2-yl)amino]cyclohexyl]methyl]
      methanesulfonamide] exerts anxiolytic- and antidepressant-like effects in rat
      models of stress sensitivity.
AB  - Neuropeptide Y (NPY) regulates physiological processes via receptor subtypes
      (Y(1), Y(2), Y(4), Y(5), and y(6)). The Y(5) receptor is well known for its role
      in appetite. Based on expression in the limbic system, we hypothesized that the
      Y(5) receptor might also modulate stress sensitivity. We identified a novel Y(5)
      receptor-selective antagonist, Lu AA33810 [N-[[trans-4-[(4,5-dihydro[1]
      benzothiepino[5,4-d]thiazol-2-yl)amino]cyclohexyl]methyl]-methanesulfonamide],
      that bound to cloned rat Y(5) receptors (K(i) = 1.5 nM) and antagonized NPY
      evoked cAMP and calcium mobilization in vitro. Lu AA33810 (3-30 mg/kg p.o.)
      blocked feeding elicited by intracerebroventricular injection of the Y(5)
      receptor-selective agonist [cPP(1-7),NPY(19-23),Ala(31),Aib(32),Gln(34)]
      hPancreatic Polypeptide in Sprague-Dawley rats. In vivo effects of Lu AA33810
      were correlated with brain exposure > or = 50 ng/g and ex vivo Y(5) receptor
      occupancy of 22 to 95%. Lu AA33810 was subsequently evaluated in models of stress
      sensitivity. In Fischer 344 rats, Lu AA33810 (30 mg/kg p.o.) attenuated increases
      in plasma ACTH and corticosterone elicited by intracerebroventricular injection
      of [cPP(1-7),NPY(19-23),Ala(31),Aib(32),Gln(34)]-hPancreatic Polypeptide. In
      Sprague-Dawley rats subjected to the social interaction test, Lu AA33810 (3-30
      mg/kg p.o.) produced anxiolytic-like effects after acute or chronic treatment. In
      Flinders sensitive line rats, chronic dosing of Lu AA33810 (10 mg/kg/day i.p.)
      produced anxiolytic-like effects in the social interaction test, plus
      antidepressant-like effects in the forced swim test. In Wistar rats exposed to
      chronic mild stress, chronic dosing of Lu AA33810 (3 and 10 mg/kg/day i.p.)
      produced antidepressant-like activity, i.e., normalization of stress-induced
      decrease in sucrose consumption. We propose that Y(5) receptors may function as
      part of an endogenous stress-sensing system to mediate social anxiety and reward
      or motivational deficits in selected rodent models.

PMID- 19098166
TI  - Periosteal chondrosarcoma.
AB  - OBJECTIVE: The purpose of this article is to identify the typical imaging
      features of periosteal chondrosarcoma on radiography, CT, and MRI. CONCLUSION:
      Periosteal chondrosarcoma is a rare low-grade malignant cartilaginous tumor
      arising from the external surface of bone. Imaging features are often specific.
      Recognizing periosteal chondrosarcoma and differentiating it from other surface
      tumors is of capital importance because the prognosis is excellent after adequate
      local surgery alone.

PMID- 19098167
TI  - Imaging the ligaments of the trapeziometacarpal joint: MRI compared with MR
      arthrography in cadaveric specimens.
AB  - OBJECTIVE: The purpose of our study was to compare the normal ligamentous anatomy
      of the trapeziometacarpal joint in cadavers on conventional MRI and MR
      arthrography and review the most common diseases and abnormalities that affect
      this articulation. MATERIALS AND METHODS: MR images of seven trapeziometacarpal
      joints of seven fresh cadaveric hands were obtained before and after
      arthrography. The MR appearances of the ligaments around the trapeziometacarpal
      joint were analyzed and correlated with corresponding anatomic sections. The
      imaging planes that allowed best analysis of these structures were determined.
      RESULTS: Five ligaments around the trapeziometacarpal joint were generally
      recognized: the dorsoradial ligament; the posterior oblique ligament; the
      intermetacarpal ligament; the ulnar collateral ligament (UCL); and both portions
      of the anterior oblique ligament, the superficial anterior oblique and deep
      anterior oblique ligaments. The former three were attached to the dorsal aspect
      and the latter three to the volar aspect of the trapeziometacarpal joint. The
      dorsoradial ligament, posterior oblique ligament, intermetacarpal ligament, and
      superficial and deep anterior oblique ligaments were best visualized in the
      sagittal plane, whereas the UCL was best visualized in the coronal plane. MR
      arthrography mainly improved visualization of the intermetacarpal ligament,
      superficial and deep anterior oblique ligaments, and UCL. CONCLUSION: MR
      arthrography improves visualization of and provides detailed information about
      the anatomy of the ligaments around the trapeziometacarpal joint. Knowledge of
      the appearance of these normal ligaments on MRI allows accurate diagnosis of
      lesions of the trapeziometacarpal ligaments and of the adjacent structures and
      aid the attending physician if and when surgery is indicated.

PMID- 19098168
TI  - MDCT angiography after open thoracic aortic surgery: pearls and pitfalls.
AB  - OBJECTIVE: The purpose of this article is to review open thoracic aortic surgical
      techniques and to describe the range of postoperative findings on CT angiography
      (CTA). CONCLUSION: An understanding of surgical thoracic aortic procedures will
      allow appropriate differentiation of normal from abnormal CTA findings on
      postoperative imaging.

PMID- 19098169
TI  - Recurrent pyogenic cholangitis: from imaging to intervention.
AB  - OBJECTIVE: The objective of this article is to familiarize the reader with the
      sonographic, CT, MR cholangiopancreatography, and ERCP appearances of recurrent
      pyogenic cholangitis and to briefly review the role of interventional radiology
      in the management of this disease. CONCLUSION: Recurrent pyogenic cholangitis is
      a complex disease, the incidence of which is increasing in Western countries.
      Radiologists should be aware of the role of imaging in the diagnosis of this
      disease and the use of imaging as a guideline for subsequent intervention.

PMID- 19098170
TI  - Intermetatarsal fat pad sign: radiographic aid to diagnosis of occult
      tarsometatarsal joint injuries.

PMID- 19098171
TI  - MRI of isolated distal fibular fractures with widened medial clear space on
      stressed radiographs: which ligaments are interrupted?
AB  - OBJECTIVE: Patient management choices in ankle fractures remain controversial
      because of ambiguities in assessing ankle stability and lack of information on
      the integrity of all supporting ligaments. Our objective was to use MRI to
      identify the range of ankle ligament injuries associated with a problematic
      subset of ankle fracture: isolated fibular fractures for which widened medial
      clear space is absent or minimal on standard ankle radiographs but evident on
      stress images. CONCLUSION: In our retrospective study of 19 patients, we have
      categorized ligament injury and found partial or complete tears in all cases in
      at least two of the four major ligament groups--usually the deltoid and
      syndesmosis groups. The anterior inferior tibiofibular ligament of the
      syndesmosis suffered complete interruption in every case. The posterior
      tibiotalar ligament of the deltoid group, a major contributor to stability, was
      generally injured but, unexpectedly, most of these tears were partial.

PMID- 19098172
TI  - Evaluation of a single-pass continuous whole-body 16-MDCT protocol for patients
      with polytrauma.
AB  - OBJECTIVE: The purpose of this study was to compare a conventional multiregional
      MDCT protocol with two continuous single-pass whole-body MDCT protocols in
      imaging of patients with polytrauma. SUBJECTS AND METHODS: Ninety patients with
      polytrauma underwent whole-body 16-MDCT with a conventional (n=30) or one of two
      single-pass (n=60) protocols. The conventional protocol included unenhanced scans
      of the head and cervical spine and contrast-enhanced helical scans (140 mL, 4
      mL/s, 300 mg I/mL) of the thorax and abdomen. The single-pass protocols consisted
      of unenhanced scans of the head followed by one-sweep acquisition from the circle
      of Willis through the pubic symphysis with a biphasic (150 mL, 6 and 4 mL/s, 300
      mg I/mL) or monophasic (110 mL, 4 mL/s, 400 mg I/mL) injection. Acquisition times
      and interval delays between head, chest, and abdominal scans were recorded.
      Contrast enhancement was measured in the aortic arch, liver, spleen, and kidney.
      Diagnostic image quality in the same areas was assessed on a 4-point scale.
      RESULTS: Median acquisition times for the single-pass protocols were
      significantly shorter (-42.5%) than the acquisition time for the conventional
      protocol. No significant differences were found in mean enhancement values in the
      aorta, liver, spleen, and kidney for the three protocols. The image quality with
      both single-pass protocols was better than that with the conventional protocol in
      assessment of the mediastinum and cervical spine (p<0.05). There was no
      significant difference between the single-pass protocols. CONCLUSION: Use of
      single-pass continuous whole-body MDCT protocols can significantly decrease
      examination time for patients with polytrauma and improve image quality compared
      with a conventional serial scan protocol. Monophasic injection with highly
      concentrated contrast medium can reduce injection flow rate and should therefore
      be preferred to a biphasic injection technique.

PMID- 19098173
TI  - Color comet-tail artifact: clinical applications.
AB  - OBJECTIVE: This article explores the circumstances under which the color comet
      tail artifact occurs and illustrates the clinical value of the artifact.
      CONCLUSION: Subtle abnormalities on gray-scale sonograms often are better
      appreciated and understood when the color comet-tail artifact is present. This
      artifact often is helpful in situations in which gray-scale imaging does not
      provide adequate information for a conclusive diagnosis. Visualization of the
      color comet-tail artifact can improve diagnostic confidence in a wide spectrum of
      clinical conditions encountered in sonographic practice.

PMID- 19098174
TI  - Advances in pediatric neuroradiology: highlights of the recent medical
      literature.
AB  - OBJECTIVE: This review is an attempt to bring some of the best articles in the
      recent pediatric neuroradiology literature to the attention of the AJR
      readership. CONCLUSION: Many advanced imaging capabilities are being brought to
      bear to noninvasively monitor physiologic changes in the abnormal pediatric
      brain. Furthermore, novel forms of analysis that are evidence-based are being
      used to better understand how imaging studies are used and the impact they have
      on clinical decision making. The reader is encouraged to read these articles in
      their entirety in order to better understand the lines of inquiry contained in
      them.

PMID- 19098175
TI  - Evaluation of the pediatric craniocervical junction on MDCT.
AB  - OBJECTIVE: The purpose of our study was to establish normal values on MDCT images
      for the measurement of various craniocervical junction relationships in children
      and to address discrepancies in the literature based on radiographic values.
      MATERIALS AND METHODS: Accepted methods of evaluating the craniocervical junction
      were used to calculate normal values in 117 normal children on MDCT images with
      multiplanar reconstructions. The basion-axial interval, basion-dens interval,
      Powers ratio, atlantodental interval, and atlantooccipital interval were measured
      in each patient and compared with accepted data based on radiographs. RESULTS:
      The basion-axial interval was difficult to reproduce on MDCT images. In 97.5% of
      patients, the basion-dens interval was less than 10.5 mm compared with 12 mm
      based on data from radiographs. Separating the patient population into those in
      whom the os terminale was ossified and those in whom it was not revealed a
      difference of 2 mm in the upper limit of normal (9.5 and 11.6 mm, respectively).
      The Powers ratio showed no significant difference compared with data obtained
      using radiographs. In 97.5% of the population, the atlantodental interval was
      less than 2.6 mm, compared with 4-5 mm measured on radiographs. The
      atlantooccipital interval showed 97.5% of the population falling below 2.5 mm at
      any point in the joint space, compared with the previously accepted value of 5
      mm. CONCLUSION: Normal values for the craniocervical junction articulations and
      relationships as seen on MDCT are different from the accepted ranges of normal
      based on radiographs. The values should be considered the normal values in the
      pediatric population on MDCT.

PMID- 19098176
TI  - Spectrum of choroid plexus lesions in children.
AB  - OBJECTIVE: The aim of this article is to review the embryology of the choroid
      plexus and the spectrum of disorders involving the choroid plexus in children and
      to illustrate their radiologic features. CONCLUSION: The choroid plexus is an
      important part of the CNS that can be the primary or secondary location for many
      congenital abnormalities or pathologic conditions such as neoplasms, infections,
      inflammatory processes, cysts, and vascular malformations.

PMID- 19098177
TI  - Imaging findings in neonatal hypoxia: a practical review.
AB  - OBJECTIVE: The findings of hypoxia in the term neonate are unique; neonatal brain
      imaging findings differ from those of older children. Evaluation of neonatal
      brain images for signs of hypoxic injury requires attention to a specific set of
      signs. CONCLUSION: Imaging findings in term neonates must be assessed according
      to different rules from those used in other age groups. Four major signs are
      proposed as a means of facilitating the diagnosis of hypoxia in the neonate.

PMID- 19098178
TI  - Brain and bone abnormalities of thanatophoric dwarfism.
AB  - OBJECTIVE: The purpose of this article is to present the imaging findings of
      skeletal and brain abnormalities in thanatophoric dwarfism, a lethal form of
      dysplastic dwarfism. CONCLUSION: The bony abnormalities associated with
      thanatophoric dwarfism include marked shortening of the tubular bones and ribs.
      Abnormal temporal lobe development is a common associated feature and can be
      visualized as early as the second trimester. It is important to assess the brains
      of fetuses with suspected thanatophoric dwarfism because the presence of
      associated brain malformations can assist in the antenatal diagnosis of
      thanatophoric dwarfism.

PMID- 19098179
TI  - Diagnostic determinants of craniocervical distraction injury in adults.
AB  - OBJECTIVE: Craniocervical distraction injury is a class of injuries that involve
      the skull base, the atlas, and the axis. Although these injuries often are overt
      imaging and clinical findings, the injury can be masked during unreliable
      physical examinations and difficult to identify during diagnostic imaging. The
      goal of this study was to identify on coronal and sagittal CT multiplanar
      reformations precise measurements and qualitative relations between anatomic
      landmarks that can help in establishing the diagnosis of craniocervical
      distraction injury. MATERIALS AND METHODS: We performed a retrospective review of
      the cases of 35 patients with craniocervical distraction injury admitted to our
      trauma center from 2000 to 2006. Two independent radiologists made several
      qualitative and quantitative anatomic assessments on reformatted CT images
      through the craniocervical junctions (skull base through C2) of the 35 patients
      and of 50 other patients sustaining blunt trauma who were discharged without
      findings of cervical spinal injury. Logistic regression, recursive partitioning,
      and multivariate analysis were performed in an attempt to find measurements that
      differentiated the groups. RESULTS: Among the patients with craniocervical
      distraction injury, statistically significant positive correlations were found in
      several measurements, including midline occiput-C1 spinolaminar distance
      (p=0.0016), midline C1-C2 spinolaminar distance (p<0.0001), basion-dens distance
      (p<0.0001), sum of condylar displacement (p=0.0002), and basion-posterior axial
      line distance (p<0.0001). CONCLUSION: Several quantitative parameters on sagittal
      and coronal multiplanar CT reformations can be used to differentiate patients
      with craniocervical distraction injury from patients without this injury.

PMID- 19098180
TI  - Correlation of neurodevelopmental features and MRI findings in infantile Krabbe's
      disease.
AB  - OBJECTIVE: The purpose of our study was to compare MRI findings with
      neurobehavioral development in infants with Krabbe's disease. MATERIALS AND
      METHODS: Nine infants with Krabbe's disease underwent a total of 19 MR studies
      during the first year of life as well as tests of mental development, gross motor
      skills, and fine motor skills (score range: 0-100) within 1 month of imaging. MR
      scans were scored using the Loes severity scale based on signal abnormality and
      atrophy, ranging from 0 (best) to 32. We performed three comparisons (Student's t
      test): each test versus total brain Loes score, fine motor and gross motor tests
      versus Loes score for the pyramidal tract, and fine motor and gross motor tests
      versus Loes score for the internal capsule. RESULTS: Mean test results were 65+/
      31 for mental development, 48+/-39 for gross motor score, 57+/-35 for fine motor
      score, and mean total brain score was 7.79+/-6.20. Correlations for total Loes
      score were -0.78 (p=0.003) for mental development, -0.74 (p=0.003) for gross
      motor function, and -0.80 (p<0.001) for fine motor function. Correlations for
      pyramidal system Loes scores were -0.73 (p=0.003) for fine motor function and 
      0.58 (p=0.028) for gross motor function. Correlation between Loes scores for
      internal capsule and fine motor function was -0.38 (p>0.05) and between Loes
      scores for internal capsule and gross motor function was -0.35 (p>0.05).
      CONCLUSION: The very good correlation between testing results and Loes scores for
      the entire brain and moderately good correlation between test results and scores
      for specific brain regions indicate the Loes scoring system likely provides a
      reasonable means for assessing prognosis and therapeutic response for infants
      with Krabbe's disease.

PMID- 19098181
TI  - Performance of preoperative sonographic staging of papillary thyroid carcinoma
      based on the sixth edition of the AJCC/UICC TNM classification system.
AB  - OBJECTIVE: The purpose of this prospective study was to evaluate the overall
      performance of sonography for staging papillary thyroid carcinoma. SUBJECTS AND
      METHODS: Ninety-four consecutive patients with papillary thyroid carcinoma
      underwent preoperative sonography. Two experienced radiologists prospectively
      evaluated primary tumors (e.g., diameter, number, presence of extrathyroidal
      invasion) and cervical lymph nodes for metastasis. A 5-point scale grading
      capsular abutment was used to evaluate the possibility of extrathyroidal
      invasion. Lymph nodes were divided into central and lateral groups according to N
      staging requirements. The sonographic criteria for lymph node metastasis were an
      absent hilum, hyperechoic change, a round shape, calcification, cystic change, or
      an abnormal color Doppler pattern. Sonographic results were correlated with
      histopathologic findings. RESULTS: One hundred twenty-seven cancers in the 94
      patients were proven after surgery. Sonography accurately identified 75.9%
      (22/29) of patients with multifocal cancer and 83.3% (15/18) of patients with
      bilateral cancers. Using a cutoff value of 50% or more of the tumor abutting the
      thyroid capsule (grade 2), the sensitivity, specificity, and accuracy of
      sonography in predicting extrathyroidal invasion were 85.3%, 70.0%, and 74.5%,
      respectively, and the overall accuracy of sonography for T staging was 67.0%
      (63/94). One hundred forty-seven cervical lymph node levels were dissected. All
      six sonographic findings were significantly more frequent in metastatic lymph
      nodes in the lateral group. However, in the central group, only two criteria
      calcification and abnormal Doppler pattern-were found to significantly predict
      the presence of metastasis. The overall accuracy of sonography for N staging was
      71.3% (67/94). CONCLUSION: Sonography is a feasible tool to use for the
      preoperative staging of papillary thyroid carcinoma.

PMID- 19098182
TI  - Normal sonographic anatomy of the posterolateral corner of the knee.
AB  - OBJECTIVE: The posterolateral corner of the knee comprises a group of structures
      that are important to knee stability. MRI is currently the standard imaging
      technique, but visualization of individual structures is often incomplete.
      Sonography allows rapid real-time assessment of these superficial structures, but
      knowledge of the anatomy is essential to allow accurate examination. CONCLUSION:
      We present an illustrated review of the sonographic anatomy of the posterolateral
      corner of the knee with MRI correlation.

PMID- 19098183
TI  - Comparison of 3-T MRI and arthroscopy of intrinsic wrist ligament and TFCC tears.
AB  - OBJECTIVE: This study assesses the sensitivity and specificity of MRI at 3 T
      compared with arthroscopy for detection of intrinsic wrist ligament and
      triangular fibrocartilage complex (TFCC) tears. MATERIALS AND METHODS: MR wrist
      images in 300 consecutive patients underwent consensus review by two radiologists
      without knowledge of arthroscopy findings. Forty-nine of 300 patients underwent
      arthroscopy. Thirty-five of these 49 patients also underwent MR arthrography.
      Scans were assessed for full-thickness scapholunate, lunatotriquetral, or TFCC
      tears. After consensus review of MR images, arthroscopy results were compared
      with MR interpretations. RESULTS: Of the 49 patients who underwent arthroscopy,
      22 had TFCC tears, 18 had scapholunate tears, and 11 had lunatotriquetral tears
      (51 total tears at arthroscopy). Nineteen of 22 TFCC tears, 16 of 18 scapholunate
      tears, and nine of 11 lunatotriquetral tears seen at arthroscopy were seen on
      MRI. Four patients had both a TFCC tear and a lunatotriquetral ligament tear. One
      patient had a scapholunate ligament tear and a TFCC tear. There were no false
      positive readings on MRI compared with arthroscopy. MR sensitivity for detection
      of TFCC tears was 86%, for detection of scapholunate tears was 89%, and for
      detection of lunatotriquetral tears was 82%. MR specificity for detection of
      tears was 100%. MR arthrography sensitivity for detection of ligament and TFCC
      tears was 100%. There were three patients in whom contrast media passed between
      joint spaces without an anatomic abnormality seen. These patients underwent
      arthroscopy with no tears seen. CONCLUSION: MRI at 3 T is sensitive and specific
      for detection of wrist ligament tears. MR arthrography is more sensitive for
      ligament evaluation but can result in false-positive findings because of
      microperforations.

PMID- 19098184
TI  - 3-T MRI of the shoulder: is MR arthrography necessary?
AB  - OBJECTIVE: The purpose of this study is to report the diagnostic sensitivity of 3
      T conventional MRI versus MR arthrography of the shoulder in the same patient
      population. MATERIALS AND METHODS: One hundred fifty consecutive conventional
      shoulder MRI and MR arthrography examinations performed on patients 50 years or
      younger who subsequently underwent arthroscopy were reviewed retrospectively by
      consensus reading by two musculoskeletal radiologists. All patients selected for
      arthroscopy had abnormal findings on clinical examination and MRI or MR
      arthrography. All 150 patients were referred from one orthopedic group. All
      patients consented to undergo both MRI and MR arthrography. None had undergone
      prior shoulder surgery. Full- or partial-thickness supraspinatus tendon tears,
      superior labral anterior-to-posterior (SLAP) tears, and anterior or posterior
      labral tears were assessed. RESULTS: Three full-thickness and nine partial
      thickness supraspinatus tendon tears, seven SLAP tears, six anterior labral
      tears, and two posterior labral tears were seen on MR arthrography but not on
      conventional MRI. All additional MR arthrography findings were confirmed at
      arthroscopy. On conventional MRI, sensitivities and specificities compared with
      arthroscopy were as follows: anterior labral tear, 83% sensitivity and 100%
      specificity; posterior labral tear, 84% and 100%; SLAP tear, 83% and 99%;
      supraspinatus tendon tear, 92% and 100%; partial-thickness articular surface
      tear, 68% and 100%; and partial-thickness bursal surface tear, 84% and 100%. On
      MR arthrography, sensitivities and specificities compared with arthroscopy were
      as follows: anterior labral tear, 98% sensitivity and 100% specificity; posterior
      labral tear, 95% and 100%; SLAP tear, 98% and 99%; supraspinatus tendon tear,
      100% and 100%; partial-thickness articular surface tear, 97% and 100%; and
      partial-thickness bursal surface tear, 84% and 100%. MR arthrography showed a
      statistical improvement in sensitivity (p<0.05) for detection of partial
      thickness articular surface supraspinatus tears, anterior labral tears, and SLAP
      tears at 3 T. CONCLUSION: In this series, MR arthrography showed statistically
      significant increased sensitivity for detection of partial-thickness articular
      surface supraspinatus tears, anterior labral tears, and SLAP tears compared with
      conventional MRI at 3 T. On the basis of the above findings, we perform 3-T MR
      arthrography on patients for whom anterior labral tears, SLAP tears, and partial
      thickness supraspinatus tendon tears are suspected clinically.

PMID- 19098185
TI  - MRI appearance of the pectinofoveal fold.
AB  - OBJECTIVE: The pectinofoveal fold is an intraarticular structure of the hip that
      has had only limited study in the clinical and anatomic literature. This fold may
      resemble a hip plica; however, symptomatic hip plicae are now being recognized
      and treated at hip arthroscopy. We wished to determine the frequency and
      appearance of the pectinofoveal fold on hip MR arthrography. By defining the
      variations in its appearance, the normal pectinofoveal fold can be distinguished
      from pathologic hip plicae. MATERIALS AND METHODS: One hundred fifty-two hip MR
      arthrography examinations of patients who subsequently underwent hip arthroscopy
      were retrospectively reviewed. Each MR examination was reviewed for the presence
      of a pectinofoveal fold. If present, the fold was measured in the
      anteroposterior, mediolateral, and superior-inferior dimensions; evaluated for
      smooth or irregular contour; and evaluated for a femoral or capsular site of
      insertion. RESULTS: The pectinofoveal fold was visualized on hip MR arthrograms
      in 144 of the 152 (95%) patients and visualized at hip arthroscopy in 150 of the
      152 (99%) patients. The average thickness of the fold was 2.6 mm (range, 1-13 mm)
      in the mediolateral dimension and 17 mm (range, 1-32 mm) in the anteroposterior
      dimension. The average length of the fold in the superior-inferior dimension was
      23.3 mm (range, 7-44 mm). The pectinofoveal fold had a smooth contour in 75 of
      the 144 (52%) patients with examinations that showed the fold and an irregular
      contour in 69 of 144 (48%) patients. The fold was found to insert onto the
      capsule in 108 of 144 (75%) patients and onto the femur in the remaining 36.
      CONCLUSION: The pectinofoveal fold should almost always be visualized at MR
      arthrography. The fold can have various appearances and attachment sites, and
      these normal variations should not be mistaken for fold abnormalities. These
      findings should be useful in distinguishing this normal structure from normal and
      pathologic plicae.

PMID- 19098186
TI  - Diagnostic utility of T1-weighted MRI characteristics in evaluation of
      osteomyelitis of the foot.
AB  - OBJECTIVE: The purpose of this study was to evaluate the diagnostic utility of
      specific characteristics on T1-weighted MR images in the diagnosis of pedal
      osteomyelitis. MATERIALS AND METHODS: The study included all adult patients who
      underwent MRI of the foot for evaluation of suspected osteomyelitis over an 11
      month period. Images were retrospectively reviewed for specific criteria on T1
      weighted images, including signal intensity of affected bone marrow (normal or
      decreased), distribution of abnormal signal intensity (subcortical or medullary),
      and pattern of involvement (hazy reticulated or confluent). The presence of
      osteomyelitis was presumed if the surgical pathologic result was positive or if
      there was lack of clinical improvement despite conservative management. Rapid
      clinical improvement with conservative management was considered an indication
      that osteomyelitis was not present. RESULTS: Images from 74 examinations were
      evaluated. In 20 cases, osteomyelitis was considered present, and in 54 it was
      presumed absent. In 19 of the 20 cases (95%) in which osteomyelitis was
      considered present, marrow T1 signal intensity was decreased, in a medullary
      distribution, and in a confluent pattern in all cases. In 30 of the 54 cases
      (56%) in which osteomyelitis was presumed absent, T1 signal intensity was
      decreased, but only five cases (9%) had a medullary distribution and confluent
      pattern. Twenty-three cases (43%) had a hazy reticulated pattern, and two cases
      (4%) had only subcortical distribution. None of the cases with a subcortical
      distribution or hazy reticulated pattern of abnormal signal intensity had
      positive results for osteomyelitis. Confluent decreased T1 marrow signal
      intensity in a medullary distribution was 95% sensitive in the prediction of
      osteomyelitis with a specificity of 91%, negative predictive value of 98%, and
      positive predictive value of 79%. CONCLUSION: Findings on T1-weighted MR images,
      specifically a confluent pattern of decreased T1 marrow signal intensity in a
      medullary distribution, correlate highly with the presence of pedal
      osteomyelitis.

PMID- 19098187
TI  - Knee dislocation in overweight patients.
AB  - OBJECTIVE: The purpose of this study was to evaluate the incidence, cause, injury
      patterns, and MRI findings in knee dislocation in patients with normal and
      increased body mass index and to determine whether obesity interferes with knee
      MRI examinations. MATERIALS AND METHODS: A retrospective study of the period from
      2000 to 2007 (90 months) was performed at a level 1 trauma center, finding a
      total of 24 patients who had sustained a knee dislocation. RESULTS: Twenty-two of
      the 24 patients underwent surgery and 19 patients had an MRI examination of
      diagnostic quality before surgery. Of the 24 patients, 11 had a body mass index
      greater than 25 and had knee dislocation due to low-energy trauma (nine due to a
      simple fall, two to a noncontact sport). Two of these 11 patients were morbidly
      obese (body mass index>40). These patients had no injuries to the popliteal
      tendon and they had no irreversible peroneal nerve injuries. Otherwise, the
      patients' injuries were in agreement with previous knee dislocation studies.
      Obesity did not interfere with knee MRI examinations. On the basis of the
      population served by our trauma center, the annual incidence of knee dislocation
      due to low-energy trauma in overweight patients is about 1.0 per million.
      CONCLUSION: The annual incidence in obese patients of knee dislocation due to low
      energy trauma is not insignificant at a level 1 trauma center. As the prevalence
      of obesity increases, the injury patterns seen in emergency departments may
      change. The radiologist should be aware that even after a simple fall, overweight
      patients may have a knee dislocation.

PMID- 19098188
TI  - CT-guided percutaneous catheter drainage of acute necrotizing pancreatitis:
      clinical experience and observations in patients with sterile and infected
      necrosis.
AB  - OBJECTIVE: The purpose of this study was to report on clinical experience with
      and observations made during primary CT-guided percutaneous catheter drainage of
      acute necrotizing pancreatitis and to compare results among patients with sterile
      and those with infected necrosis. MATERIALS AND METHODS: We reviewed clinical,
      radiologic, and bacteriologic data on 35 patients (23 men, 12 women; mean age, 50
      years; range, 21-83 years) with acute necrotizing pancreatitis refractory to
      standard medical care who underwent CT-guided percutaneous catheter drainage with
      12- to 22-French catheters. Experiences with two subgroups were compared. One
      group consisted of 22 patients, 10 with multisystem organ failure, who presented
      with sterile necrosis (median Atlanta score, 1.3; range, 0-3). The other group
      consisted of 13 patients, one with multisystem organ failure, who presented with
      infected necrosis (median Atlanta score, 0.4; range, 0-3). Differences between
      the group with sterile and the group with infected necrosis were analyzed with
      the Fisher-Holton exact and Mann-Whitney U tests. RESULTS: Among 35 patients, 17
      (49%) were treated successfully with CT-guided percutaneous catheter drainage
      alone. The effectiveness of CT-guided percutaneous catheter drainage in patients
      with sterile necrosis (11/22, 50%) was not significantly different from that of
      drainage in patients with infected necrosis (6/13, 46%). Among 11 patients with
      multisystem organ failure (10 with sterile necrosis, one with infected necrosis),
      only four (36%) were treated successfully with CT-guided percutaneous catheter
      drainage alone; five patients (45%) died. Among 24 patients without multisystem
      organ failure, 13 (54%) were treated successfully with CT-guided percutaneous
      catheter drainage alone; one patient died. CONCLUSION: In our experience, primary
      CT-guided percutaneous catheter drainage was successful for approximately one
      half of the patients with acute necrotizing pancreatitis. The presence of
      multisystem organ failure appears to be a more important indicator of outcome
      than does the presence of infection.

PMID- 19098189
TI  - Diagnostic accuracy of intraarterial and i.v. MR angiography for the detection of
      stenoses of the infrainguinal arteries.
AB  - OBJECTIVE: The objective of our study was to prospectively evaluate the
      diagnostic accuracy of intraarterial (i.a.) and i.v. MR angiography (MRA) of the
      infrainguinal arteries in comparison with the reference standard selective
      digital subtraction angiography (DSA). SUBJECTS AND METHODS: Twenty consecutive
      patients with symptomatic peripheral arterial occlusive disease (PAOD) underwent
      i.v. MRA and i.a. MRA of the infrainguinal arteries and DSA, which served as the
      reference standard. For i.v. MRA, 27 mL of gadodiamide was injected through a
      peripheral arm vein; for i.a. MRA, 30 mL of diluted contrast agent (5 mL of
      gadodiamide in 55 mL of 0.9% saline solution) was twice injected in the
      superficial femoral artery with a flow rate of 2.5 mL/s through a 5-French sheath
      that was placed on the occasion of DSA before vascular intervention. A 3D
      gradient-echo sequence was performed using a dedicated coil system on a 1.5-T MR
      scanner. Three independent blinded observers localized and quantitatively graded
      stenoses on i.v. MRA and i.a. MRA. The overall impression of image quality of
      i.v. MRA and i.a. MRA was documented using a 4-point scale (1, excellent; 4,
      poor). Interobserver agreement was calculated. RESULTS: The mean sensitivity and
      mean specificity for the detection of stenoses >or= 50% of the upper leg arteries
      (i.e., superficial femoral artery and popliteal artery) were 85.5% and 83.3% for
      i.a. MRA and 82.2% and 86.7% for i.v. MRA, respectively. The mean sensitivity and
      mean specificity for the detection of stenoses >or= 50% of the lower leg arteries
      (i.e., proximal anterior tibial artery, tibiofibular trunk, proximal posterior
      tibial artery, and proximal peroneal artery) were 91.7% and 75.0% for i.a. MRA,
      respectively, and 87.5% each for i.v. MRA. the diagnostic quality of i.a. MRA
      images and i.v. MRA images was assessed as excellent or good. CONCLUSION: i.a.
      MRA provides sensitivity and specificity for the detection of hemodynamically
      significant stenoses of the infrainguinal arteries comparable to i.v. MRA and
      therefore is a good diagnostic tool especially for MR-guided vascular
      interventions.

PMID- 19098190
TI  - Evaluation of patients with esophageal varices after endoscopic injection
      sclerotherapy using multiplanar reconstruction MDCT images.
AB  - OBJECTIVE: The purpose of our study was to assess the relationship between
      hemodynamic changes in portosystemic collaterals and the prognosis of patients
      with esophageal varices after endoscopic injection sclerotherapy using
      multiplanar reconstruction (MPR) MDCT images. SUBJECTS AND METHODS: The subjects
      of this prospective study were 53 patients who underwent endoscopic injection
      sclerotherapy for esophageal varices. We evaluated the reconstructed MPR images
      of portosystemic collaterals before and after endoscopic injection sclerotherapy.
      Patients were divided into three groups based on the rate of change in the
      diameter of the feeding vessel into complete eradication (group A), narrowing
      (group B), and no change (group C). We analyzed the relationship between
      hemodynamic change in portosystemic collaterals and prognosis. RESULTS: The left
      gastric vein, posterior gastric vein, and left gastric vein plus posterior
      gastric vein were the main feeding vessels (n=44 [83%] of patients, n=5 [9%], and
      n=4 [8%], respectively). The proportions of patients of groups A, B, and C were
      19% (n=10), 24% (n=13), and 57% (n=30), respectively. The relapse-free rates at 2
      years after endoscopic injection sclerotherapy were 100%, 65%, and 52% in groups
      A, B, and C, respectively (p<0.05). For group C, the relapse-free rate at 2 years
      after endoscopic injection sclerotherapy of patients with a large-diameter
      paraesophageal vein (>or= 3 mm, 63%) was significantly higher than in those with
      a small-diameter paraesophageal vein (<3 mm, 36%; p<0.05). However, there were no
      significant differences in the survival rate among the three groups. CONCLUSION:
      MPR MDCT images on portosystemic collaterals can accurately predict relapse of
      esophageal varices after endoscopic injection sclerotherapy.

PMID- 19098191
TI  - Predictive value of percutaneous imaging-guided biopsy of peritoneal and omental
      masses: results in 111 patients.
AB  - OBJECTIVE: The objective of our study was to determine the predictive value of
      percutaneous imaging-guided biopsy of peritoneal and omental masses. MATERIALS
      AND METHODS: A retrospective study of 111 patients who underwent biopsy of a
      peritoneal or omental mass from 1998 to 2006 was performed. Biopsy results were
      classified as diagnostic (malignant or benign) or nondiagnostic. Sensitivity,
      specificity, and negative predictive value (NPV) were calculated for all
      patients, and the Fisher-Freeman-Halton exact test was used to determine whether
      test characteristics varied by patient history (presence of a known cancer), mass
      size (<4 cm vs >or= 4 cm), and needle size (biopsies with fine needles vs
      biopsies with fine and large needles). RESULTS: The overall diagnostic rate was
      89% (99/111); there were 86 true-positive, one false-positive, six true-negative,
      and six false-negative results (sensitivity, 93% [86/92]; specificity, 86% [6/7];
      NPV, 50% [6/12]). There were no statistically significant differences between
      patients with and without known cancer. Among 79 patients with known cancer, 52
      (66%) had metastatic disease from the known cancer; in eight (10%) patients, the
      biopsy result yielded new primary cancers. Of 32 patients with no known cancer,
      23 (72%) had malignant results. Biopsy test characteristics did not differ with
      respect to mass or needle size. Minor complications were seen in three (3%)
      patients. CONCLUSION: Percutaneous imaging-guided biopsy of peritoneal and
      omental masses is a safe, effective procedure that is useful in clinical
      practice. A second malignancy was revealed in a substantial number of patients
      with a known primary cancer. A new malignancy was diagnosed in most patients
      without a history of cancer.

PMID- 19098192
TI  - CT-guided radiofrequency ablation in the treatment of recurrent rectal cancer.
AB  - OBJECTIVE: Locally recurrent rectal adenocarcinoma remains a therapeutic
      challenge that is unsatisfactorily managed by surgery and radiation therapy or
      chemotherapy. Palliative CT-guided radiofrequency ablation was used in 14
      patients with recurrent rectal adenocarcinoma who had been previously treated
      with abdominoperineal resection and radiation therapy. Follow-up CT or MRI was
      performed at 3, 6, 12, and 24 months. Pain palliation was monitored by the brief
      pain inventory (BPI). CONCLUSION: One month after radiofrequency ablation, 11
      patients reported satisfactory BPI mean scores reduction compared to baseline
      (from 7.6 to 3.4 and from 5.1 to 1.6 for worst and average pain, respectively).
      In two unresponsive patients, retreatment was successfully performed at 3 months.
      After 24 months, worst and average pain scores further decreased (to 2.6 and 0.8,
      respectively) in 10 patients, who, at imaging, showed an ablation zone covering
      the entire original lesion in two patients and incomplete ablation in eight. In
      our experience, radiofrequency ablation is a safe and effective palliative
      treatment for patients with recurrent rectal adenocarcinoma.

PMID- 19098193
TI  - CT with a computer-simulated dose reduction technique for detection of pediatric
      nephroureterolithiasis: comparison of standard and reduced radiation doses.
AB  - OBJECTIVE: The purpose of this study was to compare the diagnostic capabilities
      of standard- and reduced-dose CT in the detection of nephroureterolithiasis in
      children. MATERIALS AND METHODS: Forty-five patients 20 years old or younger
      divided into two groups weighing 50 kg or less and more than 50 kg underwent
      unenhanced 16-MDCT in the evaluation of acute flank pain. An investigational
      computer-simulated tube current reduction tool was used to produce additional 80-
      and 40-mA examination sets (total number of image sets=135). Three independent
      blinded readers ranked random images for stones (confidence scale, 1-5, least to
      most), hydronephrosis, noise-based image quality, and presence of nonrenal
      lesions. RESULTS: Compared with the standard tube current used for the original
      CT scans, there was no significant reduction (p=0.37) in detection of renal
      stones at the 80-mA setting (mean dose reduction, 67%; range, 43-81%); and at the
      40-mA setting (mean dose reduction, 82%; range, 72-90%), the detection rate was
      significantly lower (p=0.05). At the 40-mA setting, there was no significant
      difference among the children weighing 50 kg or less (p=0.4). Detection of
      ureteral stones and hydronephrosis was not significantly different at 80 and 40
      mA; however, disease frequency was low, and no definite conclusion can be made.
      CONCLUSION: Simulated dose reduction is a useful tool for determining diagnostic
      thresholds for MDCT detection of renal stones in children. Use of the 80-mA
      setting for all children and 40 mA for children weighing 50 kg or less does not
      significantly affect the diagnosis of pediatric renal stones.

PMID- 19098194
TI  - MDCT with coronal reconstruction: clinical benefit in evaluation of suspected
      acute appendicitis in pediatric patients.
AB  - OBJECTIVE: The purpose of this study was to assess the role of the addition of
      coronal reformatted images to MDCT in the evaluation of suspected acute
      appendicitis in pediatric patients. CONCLUSION: In pediatric patients with
      suspected appendicitis, the addition of coronal reformatted scans to axial images
      in MDCT increases confidence in the diagnosis or exclusion of acute appendicitis.

PMID- 19098195
TI  - Congenital diaphragmatic hernia: predictive value of MRI relative lung-to-head
      ratio compared with MRI fetal lung volume and sonographic lung-to-head ratio.
AB  - OBJECTIVE: The purpose of this study was to evaluate the prognostic accuracy of a
      new MRI-based relative lung-to-head ratio in regard to neonatal survival and need
      for extracorporeal membrane oxygenation (ECMO) in the care of fetuses with
      congenital diaphragmatic hernia (CDH) and to compare it with the previously
      described sonographic relative lung-to-head ratio and relative fetal lung volume
      assessed at antenatal MRI. MATERIALS AND METHODS: Sonographic lung-to-head ratio
      and MRI fetal lung volume were measured in 90 fetuses (mean gestational age,
      31.4+/-4.1 weeks) with CDH. Sonographic relative lung-to-head ratio and MRI
      relative fetal lung volume were assessed by expressing the observed sonographic
      lung-to-head ratio and MRI fetal lung volume as a percentage of the expected
      parameter value. The new MRI relative lung-to-head ratio was assessed as a
      percentage of the expected MRI lung-to-head ratio based on MRI fetal lung volume
      and MRI head circumference measurements. Measurements for survival and ECMO
      requirement were determined with the area under the curve (AUC). Data were
      analyzed for left-sided defects, right-sided defects, and associated liver
      herniation. RESULTS: Among fetuses with left-sided CDH, all parameters were
      excellent in determining neonatal survival and need for ECMO therapy (p <or=
      0.0027). Prognostic accuracy was best for the newly devised MRI relative lung-to
      head ratio (AUC, 0.816 and 0.807) and lowest for sonographic relative lung-to
      head ratio (AUC 0.783 and 0.703). Among fetuses with right-sided defects, the
      predictive value was lower for all parameters (AUC, 0.788-0.560). All neonates
      without liver herniation survived. CONCLUSION: Among fetuses with left-sided CDH,
      assessment of pulmonary hypoplasia based on MRI relative fetal lung volume and
      MRI relative lung-to-head ratio is excellent in prediction of neonatal survival
      and ECMO requirement. The prognostic accuracy is slightly better than that of
      sonographic relative lung-to-head ratio. Among fetuses with right-sided CDH, the
      prognostic value of all parameters is lower than those among fetuses with left
      sided defects.

PMID- 19098196
TI  - Is gadolinium necessary for MRI follow-up evaluation of cystic lesions in the
      pancreas? Preliminary results.
AB  - OBJECTIVE: The purpose of our study was to determine whether gadolinium is
      necessary in the follow-up evaluation of pancreatic cystic lesions. MATERIALS AND
      METHODS: Fifty-six patients with pancreatic cystic lesions detected on initial
      MRI and who underwent follow-up MRI were identified. Mean cyst size was 1.9 cm,
      and mean follow-up was 9.1 months. MRI included multiacquisition T1- and T2
      weighted sequences before contrast administration and 3D fat-suppressed T1
      weighted images before and after gadolinium administration. Two radiologists
      independently reviewed the entire initial examination and follow-up MRI using
      only unenhanced T1- and T2-weighted sequences from the second examination. Each
      radiologist made one of three recommendations: 1, no follow-up necessary or
      follow-up imaging in 6-12 months; 2, cyst aspiration; or 3, cyst resection. Four
      weeks later, imaging studies were reevaluated with the contrast-enhanced images
      from the second examination. A second recommendation using the same outcomes was
      made. Interobserver and intraobserver variations for the same patient were
      summarized in terms of kappa coefficients and the percentage of times the
      decisions were concordant. A 95% CI for the percentage of times management
      decisions would change without and with gadolinium was calculated. RESULTS:
      Concordance between the two different readers for the interpretations (when using
      the same MRI interpretation technique for follow-up surveillance) was 87.5% with
      a kappa coefficient to assess interobserver variation of 0.075, suggesting only
      slight agreement between the two readers. However, treatment recommendations
      provided by a single reader with and without information from the contrast
      enhanced images were discordant only 4.5% of the time. Recommendations were
      concordant without and with gadolinium 95.5% (107/112; kappa=0.67) of the time,
      suggesting substantial agreement. A retrospective consensus review of the five
      cases in which gadolinium effected a change in the observer's recommendation was
      performed. There was nothing on the gadolinium-enhanced sequences that would
      specifically alter a change in a management decision, and it is likely that the
      changes in management decisions in these five cases were simply related to
      expected variations in categorizing lesions rather than to the use of gadolinium.
      CONCLUSION: The use of gadolinium has minimal impact in the follow-up MR
      assessment of pancreatic cystic lesions.

PMID- 19098197
TI  - Three-dimensional contrast-enhanced sonography of vascular patterns of focal
      liver tumors: pilot study of visualization methods.
AB  - OBJECTIVE: We investigated visualization methods of 3D sonography with a
      perflubutane-based contrast agent in the imaging evaluation of vascular patterns
      of focal liver tumors. MATERIALS AND METHODS: Eighty-four patients with focal
      liver tumors underwent automatic scanning with 3D sonography 20-60 seconds after
      administration of a perflubutane contrast agent. The confirmed final diagnoses
      were 50 hepatocellular carcinomas, 20 metastatic lesions, nine hemangiomas, and
      five cases of focal nodular hyperplasia. Tomographic sonographic images
      reconstructed in 3D parallel slices and rendered sonographic images resembling
      angiograms were reviewed by two readers. RESULTS: Sonographic angiograms rendered
      by maximum intensity of gray values in surface smooth mode showed tumor vessels
      and early tumor enhancement. The average intensity of gray values with surface
      texture mode showed unenhanced areas within tumors. Interobserver agreement for
      classifying enhancement patterns with both tomographic sonography and sonographic
      angiography was excellent (kappa=0.84). The main pattern, intratumoral vessels
      with early homogeneous or heterogeneous tumor enhancement, had a sensitivity of
      97% (average of both readers), specificity of 94%, and positive predictive value
      (PPV) of 96% for hepatocellular carcinomas. The presence of tumor vessels with
      early peripheral ringlike tumor enhancement had a sensitivity of 90%, specificity
      of 95%, and PPV of 86% for metastatic lesions. Peripheral nodular enhancement had
      a sensitivity of 84%, specificity of 99%, and PPV of 89% for hemangioma. The
      presence of spoke-wheel arteries with early tumor enhancement had a sensitivity
      of 80%, specificity of 100%, and PPV of 100% for focal nodular hyperplasia.
      CONCLUSION: Three-dimensional sonography with a perflubutane-based contrast agent
      is useful in the evaluation of vascular patterns of focal liver tumors.

PMID- 19098198
TI  - Sonography of acute right lower quadrant pain: importance of increased
      intraabdominal fat echo.
AB  - OBJECTIVE: The purpose of our study was to assess the diagnostic usefulness of
      increased intraabdominal fat echo during the sonographic evaluation of patients
      with acute right lower quadrant (RLQ) pain. SUBJECTS AND METHODS: A total of 328
      consecutive patients (132 male and 196 female; mean age, 28+/-15 [SD] years) with
      acute RLQ pain prospectively underwent transabdominal sonography by one of three
      experienced radiologists. The radiologists prospectively graded intraabdominal
      fat echo using a 3-point scale: 1, normal; 2, slight increase; and 3, marked and
      diffuse increase. Final diagnoses were made using surgical or pathologic findings
      or by clinical follow-up. Of the 328 patients, 11 were lost to follow-up and
      excluded from analysis. Sensitivity, specificity, accuracy, positive predictive
      value (PPV), and negative predictive value (NPV) of increased intraabdominal fat
      echo were calculated for a positive final diagnosis. RESULTS: Final diagnoses
      were negative (n=103), acute appendicitis (n=137), right colonic diverticulitis
      (n=18), mesenteric lymphadenitis (n=13), enteritis (n=26), and others (n=20).
      Grades of intraabdominal fat echo were grade 1 (n=158), grade 2 (n=35), and grade
      3 (n=124). Overall, fat echo grades 2 or 3 were more frequently observed in
      patients with a positive final diagnosis (73% [157/214] vs 2% [2/103], p<0.001)
      than in those with a negative final diagnosis. Sensitivity, specificity,
      accuracy, PPV, and NPV of increased intraabdominal fat echo for a positive final
      diagnosis were 73%, 98%, 81%, 99%, and 64%. Increased intraabdominal fat echo was
      documented in 89% (122/137) of cases of acute appendicitis and in 100% (18/18) of
      cases of right colonic diverticulitis. CONCLUSION: An increased intraabdominal
      fat echo on sonography is highly specific for the presence of RLQ inflammatory
      disease.

PMID- 19098199
TI  - Detection of hepatocellular carcinoma in patients with cirrhosis: added value of
      coronal reformations from isotropic voxels with 64-MDCT.
AB  - OBJECTIVE: The purpose of our study was to prospectively assess the added value
      of isotropic coronal reformations of the liver when using 64-MDCT for the
      detection of hepatocellular carcinoma (HCC). SUBJECTS AND METHODS: Seventy-one
      consecutive patients (60 men, 11 women; mean age, 65 years) suspected of having
      HCC underwent 64-MDCT with coronal reformations. A multiphasic CT protocol that
      included unenhanced, hepatic arterial, portal venous, and equilibrium phases was
      performed. Three independent, blinded readers interpreted the transverse scan
      alone, the coronal scan alone, and the combined transverse and coronal scans for
      the presence of HCC. Sensitivity, positive predictive value, area under the
      receiver operating characteristic curve (A(z)), and interpretation time were
      calculated for each reading session. RESULTS: Seventy-six HCC nodules were
      confirmed in 48 patients using histopathologic analysis or follow-up with long
      term CT, MRI, or both (mean follow-up time, 12 months; range, 12-15 months) as
      the reference standard. Mean sensitivity, positive predictive value, and A(z)
      value for HCC detection were, respectively, 84% (191/228 readings), 91% (191/210
      readings), and 0.85 for the transverse scan alone; 83% (189/228 readings), 93%
      (189/203 readings), and 0.86 for the coronal scan alone; and 87% (198/228
      readings), 93% (198/213 readings), and 0.87 for combined interpretation of
      transverse and coronal scans. No comparisons were statistically significant.
      Forty-eight false-positive interpretations were recorded (19 for the transverse,
      14 for the coronal, and 15 for the combined interpretation sets). The reading
      session in which combined transverse and coronal scans were available for
      interpretation showed significantly superior reader confidence for HCC detection
      as well as longer interpretation times (p<0.05 for both comparisons). The average
      reading time for the combined interpretation of transverse and coronal image sets
      (mean, 12.1+/-0.8 minutes) was significantly longer than for the transverse image
      set (7.4+/-1.5 minutes) or the coronal image set (7.1+/-1.3 minutes) (p<0.01).
      CONCLUSION: With 64-MDCT, the addition of isotropic coronal reformations to
      transverse images significantly improved reader confidence for the detection of
      HCC, with no statistically significant improvement in sensitivity, positive
      predictive value, or diagnostic accuracy (as determined by the A(z) value). This
      improvement comes at the cost of a longer interpretation time.

PMID- 19098200
TI  - Cross-sectional imaging of acute and chronic gallbladder inflammatory disease.
AB  - OBJECTIVE: The purpose of this article is to provide a comprehensive review of
      the clinical and cross-sectional imaging features of a variety of acute and
      chronic gallbladder inflammatory diseases. CONCLUSION: Inflammatory gallbladder
      diseases are a common source of abdominal pain and cause considerable morbidity
      and mortality. Although acute uncomplicated cholecystitis and chronic
      cholecystitis are frequently encountered, numerous other gallbladder inflammatory
      conditions may also occur that can be readily diagnosed by cross-sectional
      imaging.

PMID- 19098201
TI  - Transabdominal sonography in assessment of the bowel in adults.
AB  - OBJECTIVE: We describe the key sonographic features and technical aspects of
      assessment of bowel disorders in adults. CONCLUSION: Initial imaging with
      transabdominal sonography in the radiologic evaluation of bowel disease in adults
      often is reserved for patients with equivocal historical, physical, and
      laboratory findings related to the gastrointestinal tract. Because of technologic
      advances and accumulated experience in interpretation of the images, sonography
      yields substantial information about gastrointestinal disorders.

PMID- 19098202
TI  - Timed efficiency of interpretation of digital and film-screen screening
      mammograms.
AB  - OBJECTIVE: Our objective was to compare interpretation speeds for digital and
      film-screen screening mammograms to test whether other variables might affect
      interpretation times and thus contribute to the apparent difference in
      interpretation speed between digital mammograms and film-screen mammograms, and
      to test whether the use of digital rather than film comparison studies might
      result in significant time savings. MATERIALS AND METHODS: Four readers were
      timed in the course of actual clinical interpretation of digital mammograms and
      film-screen mammograms. Interpretation times were compared for subgroups of
      studies based on the interpretation of the study by BI-RADS code, the number of
      images, the presence or absence of comparison studies and the type of comparison
      study, and whether the radiologist personally selected and hung additional films;
      the same comparisons were made among individual readers. RESULTS: For all four
      readers, mean interpretation times were longer for digital mammograms than for
      film-screen mammograms, with differences ranging from 76 to 202 seconds. The
      difference in interpretation speed between digital and film-screen mammograms was
      independent of other variables. Digital mammogram interpretation times were
      significantly longer than film-screen mammogram interpretation times regardless
      of whether the digital mammograms were matched with film or digital comparison
      studies. CONCLUSION: In screening mammography interpretation, digital mammograms
      take longer to read than film-screen mammograms, independent of other variables.
      Exclusive use of digital comparison studies may not cause interpretation times to
      drop enough to approach the interpretation time required for film-screen
      mammograms.

PMID- 19098203
TI  - Sonographic surveillance for the detection of contralateral metachronous breast
      cancer in an Asian population.
AB  - OBJECTIVE: This study was designed to assess the diagnostic indexes of
      sonographic surveillance with mammography for the detection of metachronous
      contralateral breast cancer. MATERIALS AND METHODS: Between January 2003 and
      December 2003, 1,706 breast sonographic examinations were performed by three
      radiologists in 1,256 Asian women with a history of surgery for breast cancer in
      one breast as an adjunct screening test to mammography in an academic medical
      center. We evaluated the biopsy recommendation rate, a diagnostic index, of the
      combination of whole-breast sonography and mammography for the detection of
      contralateral metachronous breast cancers and the positive predictive value (PPV)
      of this biopsy recommendation rate. RESULTS: Based on 1,706 examinations in 1,256
      women, the biopsy recommendation rate was 3.5% per patient and 2.6% per
      examination. The PPV of the biopsy recommendation rate was 41.0% with 18 breast
      cancers diagnosed (cancer detection rate, 1.4% per patient and 1.1% per
      examination). Among these cancers, two were detected on sonography alone. One
      false-negative cancer was found on the next sonographic examination but could not
      be seen on the next mammographic examination. CONCLUSION: With a false-negative
      rate of only 0.06% and a PPV of 41.0% for the biopsy recommendation rate, our
      results suggest that annual sonography could be a useful adjunctive tool to
      mammography for the detection of metachronous contralateral cancers.

PMID- 19098204
TI  - Frequency and upgrade rates of atypical ductal hyperplasia diagnosed at
      stereotactic vacuum-assisted breast biopsy: 9-versus 11-gauge.
AB  - OBJECTIVE: Our goals were to determine the frequency and upgrade rate for
      atypical ductal hyperplasia (ADH) diagnosed with stereotactic 9-gauge vacuum
      assisted breast biopsy and to compare the frequencies and upgrade rates of ADH
      between 9- and 11-gauge vacuum-assisted breast biopsy. MATERIALS AND METHODS: We
      retrospectively reviewed the pathology results of 991 consecutive 9- or 11-gauge
      stereotactic vacuum-assisted breast biopsy procedures from February 2001 through
      June 2006 and identified lesions diagnosed as ADH. The final diagnosis after
      surgical excision was determined from medical records. The frequencies and
      upgrade rates to carcinoma were calculated for all ADH lesions and compared
      between 9- and 11-gauge procedures. The number of core samples was recorded and
      compared. RESULTS: One hundred forty-one of 991 (14.2%) lesions yielded a
      diagnosis of ADH at 9- or 11-gauge stereotactic vacuum-assisted breast biopsy.
      Upgrade to ductal carcinoma in situ or invasive carcinoma occurred in 26 of 123
      (21.1%) patients. The frequency of ADH was 83 of 600 (13.8%) lesions for 9-gauge
      and 58 of 391 (14.8%) lesions for 11-gauge vacuum-assisted breast biopsy. The 9
      gauge upgrade rate was 16 of 74 (21.6%) lesions compared with 10 of 49 (20.4%)
      lesions for 11-gauge vacuum-assisted breast biopsy. There was no significant
      difference between the number of core samples obtained with each device (p=0.40).
      Neither the frequency of ADH (p=0.66) nor the upgrade rates (p=0.87) were
      significantly different between 9- and 11-gauge vacuum-assisted breast biopsy.
      CONCLUSION: Compared with an 11-gauge vacuum-assisted breast biopsy device, the
      use of a larger 9-gauge vacuum-assisted breast biopsy needle does not decrease
      the upgrade rate of ADH. Our frequency of ADH at vacuum-assisted breast biopsy is
      higher than any previously reported and may reflect regional differences in the
      incidence of breast cancer or practice patterns of the pathologist.

PMID- 19098205
TI  - Traditional clinical risk assessment tools do not accurately predict coronary
      atherosclerotic plaque burden: a CT angiography study.
AB  - OBJECTIVE: The objective of our study was to determine the degree to which
      Framingham risk estimates and the National Cholesterol Education Program (NCEP)
      Adult Treatment Panel III core risk categories correlate with total coronary
      atherosclerotic plaque burden (calcified and noncalcified) as estimated on
      coronary CT angiograms. MATERIALS AND METHODS: Coronary CT angiography was
      performed in 1,653 patients (1,089 men, 564 women) without a history of coronary
      heart disease (mean age+/-SD: men, 51.6+/-9.7 years; women, 56.9+/-10.5 years).
      The most common reasons for the examination were hypercholesterolemia, family
      history, hypertension, smoking, and atypical chest pain. The coronary tree was
      divided into 16 segments; four different methods were used to quantify the amount
      of atherosclerotic plaque or the degree of stenosis in each segment, and segment
      scores were combined to give total scores. Framingham risk estimates and NCEP
      risk categories were calculated for each patient. RESULTS: Correlation of plaque
      scores with the Framingham 10-year risk estimates were modest: Spearman's rho was
      0.49-0.55. For all comparisons of NCEP risk categories to plaque score
      categories, the proportion of raw agreement, p(0), was less than 0.50. Cohen's
      kappa ranged from 0.18 to 0.20. Overall, 21% of the patients would have their
      perceived need for statins changed by using the coronary CTA plaque estimates in
      place of the NCEP core risk categories; 26% of the patients on statins had no
      detectable plaque. CONCLUSION: Coronary risk stratification using a risk factor
      only-based scheme is a weak discriminator of the overall atherosclerotic plaque
      burden in individual patients. Patients with little or no plaque might be
      subjected to lifelong drug therapy, whereas many others with substantial plaque
      might be undertreated or not treated at all.

PMID- 19098206
TI  - Radiation dose savings for adult pulmonary embolus 64-MDCT using bismuth breast
      shields, lower peak kilovoltage, and automatic tube current modulation.
AB  - OBJECTIVE: The purpose of this study was to assess whether radiation dose savings
      using a lower peak kilovoltage (kVp) setting, bismuth breast shields, and
      automatic tube current modulation could be achieved while preserving the image
      quality of MDCT scans obtained to assess for pulmonary embolus (PE). MATERIALS
      AND METHODS: CT angiography (CTA) examinations were performed to assess for the
      presence or absence of pulmonary artery emboli using a 64-MDCT scanner with
      automatic tube current modulation (noise level=10 HU), two kVp settings (120 and
      140 kVp), and bismuth breast shields. Absorbed organ doses were measured using
      anthropomorphic phantoms and metal oxide semiconductor field effect transistor
      (MOSFET) detectors. Image quality was assessed quantitatively as well as
      qualitatively in various anatomic sites of the thorax. RESULTS: Using a lower kVp
      (120 vs 140 kVp) and automatic tube current modulation resulted in a dose savings
      of 27% to the breast and 47% to the lungs. The use of a lower kVp (120 kVp),
      automatic tube current modulation, and bismuth shields placed directly on the
      anterior chest wall reduced absorbed breast and lung doses by 55% and 45%,
      respectively. Qualitative assessment of the images showed no change in image
      quality of the lungs and mediastinum when using a lower kVp, bismuth shields, or
      both. CONCLUSION: The use of bismuth breast shields together with a lower kVp and
      automatic tube current modulation will reduce the absorbed radiation dose to the
      breast and lungs without degradation of image quality to the organs of the thorax
      for CTA detection of PE.

PMID- 19098207
TI  - Acute myocarditis: noninvasive evaluation with cardiac MRI and transthoracic
      echocardiography.
AB  - OBJECTIVE: The diagnosis of acute myocarditis is challenging. Nonspecific
      clinical presentation and an overlap with the diagnosis of acute myocardial
      infarction present a diagnostic dilemma. The purpose of this article is to
      describe the role of cardiac MRI and transthoracic echocardiography (TTE) in the
      diagnosis of acute myocarditis. MATERIALS AND METHODS: Thirty-two sequential
      patients (all male; average age, 33 years) with clinically suspected myocarditis
      were included. All patients underwent cardiac MRI with sequences dedicated for
      the evaluation of myocardial delayed enhancement and TTE for the evaluation of
      wall motion abnormalities (WMAs). Nine patients were excluded because of
      diagnosis of acute myocardial infarction (n=2) or inadequate cardiac MRI
      technique (n=7). Retrospective analysis of the images of the remaining 23
      patients was performed. RESULTS: An epicardial pattern of abnormal patchy
      myocardial delayed enhancement was seen on cardiac MRI in 21 of 23 (91%)
      patients. WMAs were seen on TTE in eight of 23 (35%) patients. Regional rather
      than global involvement was seen mainly in the inferolateral segments, with a
      predominance in the midventricular portion. CONCLUSION: Cardiac MRI might have a
      greater impact than TTE in confirming the presence of acute myocarditis and
      evaluating the extent of myocardial involvement. Cardiac MRI provides noninvasive
      imaging that may obviate invasive procedures such as coronary catheter
      angiography or endomyocardial biopsy.

PMID- 19098208
TI  - Cardiac MRI and pulmonary MR angiography of sinus venosus defect and partial
      anomalous pulmonary venous connection in cause of right undiagnosed ventricular
      enlargement.
AB  - OBJECTIVE: Patients may be referred for cardiology assessment because of an
      enlarged right ventricle (RV) with no cause apparent on echocardiography. Cardiac
      MRI can contribute to the management of these patients by detecting sinus venosus
      defect or partial anomalous pulmonary venous connection (PAPVC). We sought to
      show how often sinus venosus defect or PAPVC was detected on MRI in patients with
      an enlarged RV without a previously established definite diagnosis. MATERIALS AND
      METHODS: First cardiac MRI scans obtained over a 4-year period in adults with an
      undiagnosed cause of RV enlargement were searched for the MRI diagnosis of sinus
      venosus defect or PAPVC. RESULTS: Thirty-seven patients (25 female, 12 male) met
      the study criteria. Nineteen patients had a cardiac MRI diagnosis of sinus
      venosus defect, with PAPVC being present in 95% of those patients. All PAPVCs
      associated with sinus venosus defect were from the right side. Eleven of the 19
      patients with sinus venosus defect underwent surgery at our institution. Sinus
      venosus defect was confirmed in all 11 cases. Of the 37 patients, 36 had PAPVC,
      which was right-sided in 27 patients (75%), left-sided in seven patients (19.4%),
      and bilateral in two patients (5.6%). Three patients had scimitar veins. The
      common defects associated with PAPVC were sinus venosus defect in 18 patients
      (50%) and secundum atrial septal defect in six patients (17%). CONCLUSION: This
      article about cardiac MRI in adults with sinus venosus defect and PAPVC shows
      that cardiac MRI can reliably detect and quantify these lesions when other
      methods have not provided a complete diagnosis for the cause of right heart
      enlargement.

PMID- 19098209
TI  - Quantitative CT in chronic obstructive pulmonary disease: inspiratory and
      expiratory assessment.
AB  - OBJECTIVE: The purpose of this study was to determine whether measurements of
      lung attenuation at inspiration and expiration obtained from 3D lung
      reconstructions reflect the severity of chronic obstructive pulmonary disease.
      SUBJECTS AND METHODS: Seventy-six patients with chronic obstructive pulmonary
      disease underwent MDCT with 3D postprocessing at full inspiration and full
      expiration. Inspiratory and expiratory mean lung density, percentage of lung
      volume with attenuation values less than -910 HU and -950 HU at inspiration and
      expiration, expiratory to inspiratory mean lung density ratio, and fifth and 15th
      percentiles of the lung attenuation distribution curve at inspiration and
      expiration were measured. RESULTS: When forced expiratory volume in the first
      second of expiration (FEV(1)) was 50% or greater than predicted value, mean lung
      density and lower attenuation volume measured from inspiratory MDCT scans
      correlated better with FEV(1) and ratio of FEV(1) to forced vital capacity (FVC)
      than did those from expiratory scans. When FEV(1) was less than 50% of predicted
      value, mean lung density and lower attenuation volume measured from expiratory
      MDCT scans correlated better with FEV(1) and ratio of residual volume to total
      lung capacity than did those values from inspiratory scans. Fifth percentile and
      15th percentile of the lung attenuation distribution curve at both full
      inspiration and full expiration correlated well with FEV(1)/FVC and diffusing
      capacity of the lung for carbon monoxide as a percentage of predicted value but
      not well with FEV(1) as a percentage of predicted value regardless of FEV(1).
      CONCLUSION: Measurements of lung attenuation obtained at inspiration and visual
      score better reflect abnormal results of pulmonary function tests in patients
      with less severe chronic obstructive pulmonary disease than do measurements
      obtained at expiration. Measurements of lung attenuation obtained at expiration
      better reflect pulmonary function abnormalities in patients with severe chronic
      obstructive pulmonary disease.

PMID- 19098210
TI  - Cone-beam technique for 64-MDCT of lung: image quality comparison with stepwise
      (step-and-shoot) technique.
AB  - OBJECTIVE: The purpose of this study was to use phantom and patient data acquired
      with 64-MDCT to compare the image quality and characteristics of helical high
      resolution CT images obtained with cone-beam reconstruction with those of
      stepwise high-resolution CT images obtained with fan-beam reconstruction.
      SUBJECTS AND METHODS: We reconstructed helical high-resolution CT images with
      cone-beam technique and stepwise high-resolution CT images with fan-beam
      technique. In the phantom study, we measured high-contrast spatial resolution and
      image noise using a phantom. Streak artifact was evaluated by five radiologists
      using the phantom. In the clinical phase of the study, two radiologists
      independently evaluated high-resolution helical and stepwise CT images of the
      lung fields of 30 patients with diffuse lung disease. Using a 3-point ordinal
      scale, the radiologists assessed the sharpness of peripheral vessels and
      interlobular fissures, artifacts, and graininess in the lung fields; overall
      image quality; and the sharpness of the contour of the left ventricle. RESULTS:
      In high-contrast spatial resolution, the contrast curves in each spatial
      frequency were similar on the helical and stepwise images. In the clinical study,
      there was no statistically significant difference between helical and stepwise
      images with respect to sharpness of the contour of the left ventricle, peripheral
      vessels, or interlobular fissures (p>0.05). With respect to streak artifacts and
      graininess in the lung fields, helical images received a significantly higher
      quality grade than did stepwise images (p<0.05). CONCLUSION: Our phantom and
      clinical evaluation showed that the quality of high-resolution CT images of the
      lung obtained with helical scanning was comparable with the quality of stepwise
      scans.

PMID- 19098211
TI  - Quantitative molecular imaging of viral therapy for pancreatic cancer using an
      engineered measles virus expressing the sodium-iodide symporter reporter gene.
AB  - OBJECTIVE: Our objectives were to, first, determine the oncolytic potential of an
      engineered measles virus expressing the sodium-iodide symporter gene (MV-NIS) for
      intratumoral (i.t.) therapy of pancreatic cancer and, second, evaluate NIS as a
      reporter gene for in vivo monitoring and quantitation of MV-NIS delivery, viral
      spread, and gene expression in this tumor model. MATERIALS AND METHODS: Cultured
      human pancreatic cancer cells were infected with MV-NIS. Light microscopy, cell
      viability, and iodide uptake assays were used to confirm viral infection and NIS
      gene expression and function in vitro. Human pancreatic tumor xenografts were
      established in mice and infected via i.t. MV-NIS injections. NIS-mediated i.t.
      iodide uptake was quantitated by (123)I micro-SPECT/CT. i.t. MV-NIS infection was
      confirmed by immunohistochemistry of excised pancreatic xenografts. The oncolytic
      efficacy of MV-NIS was determined by measurement of tumor growth and mouse
      survival. RESULTS: Infection of human pancreatic cancer cell lines with MV-NIS in
      vitro resulted in syncytia formation, marked iodide uptake, and ultimately cell
      death. Tumor xenografts infected with MV-NIS concentrated radioiodine, allowing
      serial quantitative imaging with (123)I micro-SPECT/CT. i.t. MV-NIS therapy of
      human pancreatic cancer xenografts resulted in a significant reduction in tumor
      volume and increased survival time of the treated mice compared with the control
      mice. CONCLUSION: MV-NIS efficiently infects human pancreatic tumor cells and
      results in sufficient radioiodine uptake to enable noninvasive serial imaging and
      quantitation of the intensity, distribution, and time course of NIS gene
      expression. MV-NIS also shows oncolytic activity in human pancreatic cancer
      xenografts: Tumor growth is reduced and survival is increased in mice treated
      with the virus.

PMID- 19098212
TI  - Spectrum of 18F-FDG PET/CT findings in oncology-related recurrent laryngeal nerve
      palsy.
AB  - OBJECTIVE: The objective of our study was to review recurrent laryngeal nerve
      (RLN) anatomy and describe the typical (18)F-FDG (FDG) PET/CT appearance of vocal
      cord paresis due to oncology-related RLN injury including a spectrum of
      presentations, causes, and sites of nerve injury. CONCLUSION: Oncology-related
      RLN palsy may be caused by direct tumor invasion or its therapy. FDG PET/CT
      findings should be recognized to avoid misdiagnosis. Laryngoscopy confirms the
      suspected diagnosis and excludes primary vocal cord neoplasm.

PMID- 19098213
TI  - MDCT of the ovarian vein: normal anatomy and pathology.
AB  - OBJECTIVE: We intend to show the MDCT findings of normal ovarian (gonadal) vein
      anatomy and associated disorders, including the "ovarian vascular pedicle" sign,
      phlebolith, reflux, pelvic congestion syndrome, thrombosis, stenosis, and
      occlusion. CONCLUSION: Volume-rendered images and curved planar reformatted
      images can be used to show the ovarian veins. MDCT findings allow the diagnosis
      of various ovarian vein disorders in patients with abdominal and pelvic pain,
      pulmonary thromboembolism, and pelvic mass.

PMID- 19098214
TI  - Adrenal pheochromocytoma with surrounding brown fat stimulation.

PMID- 19098215
TI  - The longitudinal association of adolescent dating violence with psychiatric
      disorders and functioning.
AB  - While the prevalence, correlates and mental health impacts of intimate partner
      violence are well documented in adolescents and young adults, fewer studies have
      considered physical dating violence among clinical samples of help-seeking young
      people. In a sample of 98 young people aged 15-24 years (54% females) referred to
      a specialist public youth mental health service, we examined the 12-month
      prevalence of physical violence inflicted by an intimate partner and its
      relationship with psychiatric disorders and psychosocial functioning. The
      reported prevalence of dating violence in the 12 months prior to referral was
      13%. Physical dating violence reported at referral was associated with poorer
      psychosocial functioning, substance dependence and comorbid Axis I diagnoses at 6
      month follow-up. These findings suggest that youth mental health services are
      well positioned not only to screen for dating violence but to intervene to
      ameliorate the mental health consequences of abuse and to prevent further
      violence.

PMID- 19098216
TI  - Potential to reduce Escherichia coli shedding in cattle feces by using sainfoin
      (Onobrychis viciifolia) forage, tested in vitro and in vivo.
AB  - There is a growing concern about the presence of pathogens in cattle manure and
      its implications on human and environmental health. The phytochemical-rich forage
      sainfoin (Onobrychis viciifolia) and purified phenolics (trans-cinnamic acid, p
      coumaric acid, and ferulic acid) were evaluated for their ability to reduce the
      viability of pathogenic Escherichia coli strains, including E. coli O157:H7. MICs
      were determined using purified phenolics and acetone extracts of sainfoin and
      alfalfa (Medicago sativa), a non-tannin-containing legume. Ground sainfoin or
      pure phenolics were mixed with fresh cattle feces and inoculated with a
      ciprofloxacin-resistant strain of E. coli, O157:H7, to assess its viability at 
      20 degrees C, 5 degrees C, or 37 degrees C over 14 days. Forty steers were fed
      either a sainfoin (hay or silage) or alfalfa (hay or silage) diet over a 9-week
      period. In the in vitro study, the MICs for coumaric (1.2 mg/ml) and cinnamic
      (1.4 mg/ml) acids were 10- to 20-fold lower than the MICs for sainfoin and
      alfalfa extracts. In the inoculated feces, the -20 degrees C treatment had death
      rates which were at least twice as high as those of the 5 degrees C treatment,
      irrespective of the additive used. Sainfoin was less effective than coumaric acid
      in reducing E. coli O157:H7 Cip(r) in the inoculated feces. During the animal
      trial, fecal E. coli numbers declined marginally in the presence of sainfoin
      (silage and hay) and alfalfa silage but not in the presence of hay, indicating
      the presence of other phenolics in alfalfa. In conclusion, phenolic-containing
      forages can be used as a means of minimally reducing E. coli shedding in cattle
      without affecting animal production.

PMID- 19098218
TI  - Bovine Campylobacter jejuni strains differ from human and chicken strains in an
      analysis of certain molecular genetic markers.
AB  - The association of four new genetic markers with a chicken, bovine, or human host
      was studied among 645 Campylobacter jejuni isolates. The gamma-glutamate
      transpeptidase gene and dmsA were common in human and chicken isolates but
      uncommon among bovine isolates. In the t test, bovine isolates differed
      significantly (P < 0.05) from human and chicken isolates.

PMID- 19098217
TI  - How diverse is the genus Wolbachia? Multiple-gene sequencing reveals a putatively
      new Wolbachia supergroup recovered from spider mites (Acari: Tetranychidae).
AB  - At least 20% of all arthropods and some nematode species are infected with
      intracellular bacteria of the genus Wolbachia. This highly diverse genus has been
      subdivided into eight "supergroups" (A to H) on the basis of nucleotide sequence
      data. Here, we report the discovery of a new Wolbachia supergroup recovered from
      the spider mite species Bryobia species V (Acari: Tetranychidae), based on the
      sequences of three protein-coding genes (ftsZ, gltA, and groEL) and the 16S rRNA
      gene. Other tetranychid mites possess supergroup B Wolbachia strains. The
      discovery of another Wolbachia supergroup expands the known diversity of
      Wolbachia and emphasizes the high variability of the genus. Our data also clarify
      the existing supergroup structure and highlight the use of multiple gene
      sequences for robust phylogenetic analysis. In addition to previous reports of
      recombination between the arthropod-infecting supergroups A and B, we provide
      evidence for recombination between the nematode-infecting supergroups C and D.
      Robust delineation of supergroups is essential for understanding the origin and
      spread of this common reproductive parasite and for unraveling mechanisms of host
      adaptation and manipulation across a wide range of hosts.

PMID- 19098219
TI  - Environmental isolates of Burkholderia pseudomallei in Ceara State, northeastern
      Brazil.
AB  - Melioidosis has been considered an emerging disease in Brazil since the first
      cases were reported to occur in the northeast region. This study investigated two
      municipalities in Ceara state where melioidosis cases have been confirmed to
      occur. Burkholderia pseudomallei was isolated in 26 (4.3%) of 600 samples in the
      dry and rainy seasons.

PMID- 19098220
TI  - Characterization of the complete zwittermicin A biosynthesis gene cluster from
      Bacillus cereus.
AB  - Bacillus cereus UW85 produces the linear aminopolyol antibiotic zwittermicin A
      (ZmA). This antibiotic has diverse biological activities, such as suppression of
      disease in plants caused by protists, inhibition of fungal and bacterial growth,
      and amplification of the insecticidal activity of the toxin protein from Bacillus
      thuringiensis. ZmA has an unusual chemical structure that includes a d amino acid
      and ethanolamine and glycolyl moieties, as well as having an unusual terminal
      amide that is generated from the modification of the nonproteinogenic amino acid
      beta-ureidoalanine. The diverse biological activities and unusual structure of
      ZmA have stimulated our efforts to understand how this antibiotic is
      biosynthesized. Here, we present the identification of the complete ZmA
      biosynthesis gene cluster from B. cereus UW85. A nearly identical gene cluster is
      identified on a plasmid from B. cereus AH1134, and we show that this strain is
      also capable of producing ZmA. Bioinformatics and biochemical analyses of the ZmA
      biosynthesis enzymes strongly suggest that ZmA is initially biosynthesized as
      part of a larger metabolite that is processed twice, resulting in the formation
      of ZmA and two additional metabolites. Additionally, we propose that the
      biosynthesis gene cluster for the production of the amino sugar kanosamine is
      contained within the ZmA biosynthesis gene cluster in B. cereus UW85.

PMID- 19098221
TI  - Cytosine deaminase as a negative selection marker for gene disruption and
      replacement in the genus Streptomyces and other actinobacteria.
AB  - We developed a novel negative selection system for actinobacteria based on
      cytosine deaminase (CodA). We constructed vectors that include a synthetic gene
      encoding the CodA protein from Escherichia coli optimized for expression in
      Streptomyces species. Gene disruption and the introduction of an unmarked in
      frame deletion were successfully achieved with these vectors.

PMID- 19098222
TI  - Pseudomonas savastanoi pv. savastanoi contains two iaaL paralogs, one of which
      exhibits a variable number of a trinucleotide (TAC) tandem repeat.
AB  - In this study, Pseudomonas savastanoi pv. savastanoi isolates were demonstrated
      to contain two iaaL paralogs, which are both chromosomally located in most
      strains. Comparative analysis of iaaL nucleotide sequences amplified from these
      two paralogs revealed that one paralog, iaaL(Psn), is 100% identical to iaaL from
      P. savastanoi pv. nerii, while the other paralog, iaaL(Psv), exhibited 93%
      identity to iaaL from Pseudomonas syringae pv. tomato (iaaL(Pto)). A 3-nucleotide
      motif (TAC) comprised of 3 to 15 repeats, which remained stable after propagation
      of the strains in olive plants, was found in iaaL(Psv). Based on the observed
      nucleotide sequence variations, a restriction fragment length polymorphism assay
      was developed that allowed differentiation among iaaL(Psn), iaaL(Psv), and
      iaaL(Pto)(.) In addition, reverse transcriptase PCR on total RNA from P.
      savastanoi pv. savastanoi strains demonstrated that both iaaL(Psv) and iaaL(Psn)
      containing 14 or fewer TAC repeats are transcribed. Capillary electrophoresis
      analysis of PCR-amplified DNA fragments containing the TAC repeats from iaaL(Psv)
      allowed the differentiation of P. savastanoi pv. savastanoi isolates.

PMID- 19098223
TI  - Detection of an allele conferring resistance to Bacillus sphaericus binary toxin
      in Culex quinquefasciatus populations by molecular screening.
AB  - The activity of the Bacillus sphaericus binary (Bin) toxin on Culex
      quinquefasciatus larvae depends on its specific binding to the Cqm1 receptor, a
      midgut membrane-bound alpha-glucosidase. A 19-nucleotide deletion in the cqm1
      gene (cqm1(REC)) mediates high-level resistance to Bin toxin. Here, resistance in
      nontreated and B. sphaericus-treated field populations of C. quinquefasciatus was
      assessed through bioassays as well as a specific PCR assay designed to detect the
      cqm1(REC) allele in individual larvae. Resistance ratios at 90% lethal
      concentration, gathered through bioassays, were close to 1 and indicate that the
      selected populations had similar levels of susceptibility to B. sphaericus,
      comparable to that of a laboratory colony. A diagnostic PCR assay detected the
      cqm1(REC) allele in all populations investigated, and its frequency in two
      nontreated areas was 0.006 and 0.003, while the frequency in the B. sphaericus
      treated population was significantly higher. Values of 0.053 and 0.055 were
      detected for two distinct sets of samples, and homozygote resistant larvae were
      found. Evaluation of Cqm1 expression in individual larvae through alpha
      glucosidase assays corroborated the allelic frequency revealed by PCR. The data
      from this study indicate that the cqm1(REC) allele was present at a detectable
      frequency in nontreated populations, while the higher frequency in samples from
      the treated area is, perhaps, correlated with the exposure to B. sphaericus. This
      is the first report of the molecular detection of a biolarvicide resistance
      allele in mosquito populations, and it confirms that the PCR-based approach is
      suitable to track such alleles in target populations.

PMID- 19098224
TI  - Involvement of SMRT corepressor in transcriptional repression by the vitamin D
      receptor.
AB  - To repress the expression of target genes, the unliganded nuclear receptor
      generally recruits the silencing mediator of retinoid and thyroid hormone
      receptor (SMRT)/nuclear receptor corepressor via its direct association with the
      conserved motif within bipartite nuclear receptor-interaction domains (IDs) of
      the corepressor. Here, we investigated the involvement of the SMRT corepressor in
      transcriptional repression by the unliganded vitamin D receptor (VDR). Using
      small interference RNA against SMRT in human embryonic kidney 293 cells, we
      demonstrated that SMRT is involved in the repression of the VDR-target genes,
      osteocalcin and vitamin D(3) 24-hydroxylase in vivo. Consistent with this, VDR
      and SMRT are recruited to the vitamin D response element of the endogenous
      osteocalcin promoter in the absence of 1alpha,25-(OH)(2)D(3) in chromatin
      immunoprecipitation assays. To address the involvement of the VDR-specific
      interaction of SMRT in this repression, we identified the molecular determinants
      of the interaction between VDR and SMRT. Interestingly, VDR specifically
      interacts with ID1 of the SMRT/nuclear receptor corepressor and that ID1 is
      required for their stable interaction. We also identified specific residues in
      the SMRT-ID1 that are required for VDR binding, using the one- plus two-hybrid
      system, a novel genetic selection method for specific missense mutations that
      disrupt protein-protein interactions. These mutational studies revealed that VDR
      interaction requires a wide range of the residues within and outside the extended
      helix motif of SMRT-ID1. Notably, SMRT mutants defective in the VDR interaction
      were also defective in the repression of endogenous VDR-target genes, indicating
      that the SMRT corepressor is directly involved in the VDR-mediated repression in
      vivo via an ID1-specific interaction with the VDR.

PMID- 19098225
TI  - Acute appendicitis in young children: cost-effectiveness of US versus CT in
      diagnosis--a Markov decision analytic model.
AB  - PURPOSE: To compare the cost-effectiveness of different imaging strategies in the
      diagnosis of pediatric appendicitis by using a decision analytic model. MATERIALS
      AND METHODS: Approval for this retrospective study based on literature review was
      not required by the institutional Research Ethics Board. A Markov decision model
      was constructed by using costs, utilities, and probabilities from the literature.
      The risk of radiation-induced cancer was modeled by using the Biological Effects
      of Ionizing Radiation VII report, which is based primarily on data from atomic
      bomb survivors. The three imaging strategies were ultrasonography (US), computed
      tomography (CT), and US followed by CT if the initial US study was negative. The
      model simulated the short-term and long-term outcomes of the patients,
      calculating the average quality-adjusted life span and health care costs.
      RESULTS: For a single abdominal CT study in a 5-year-old child, the lifetime risk
      of radiation-induced cancer would be 26.1 per 100,000 in female and 20.4 per
      100,000 in male patients. In the base-case analysis, US followed by CT was the
      most costly and most effective strategy, CT was the second-most costly and second
      most effective strategy, and US was the least costly and least effective
      strategy. The incremental cost-effectiveness ratios (ICERs) of CT to US and of US
      followed by CT to US were both well below the societal willingness-to-pay
      threshold of $50,000 (in U.S. dollars). The ICER of US followed by CT to CT was
      less than $10,000 in both male and female patients. CONCLUSION: In a Markov-based
      decision model of pediatric appendicitis, the most cost-effective method of
      imaging pediatric appendicitis was to start with a US study and follow each
      negative US study with a CT examination.

PMID- 19098226
TI  - Triple-layer appearance of Brodmann area 4 at thin-section double inversion
      recovery MR imaging.
AB  - PURPOSE: To investigate whether thin-section axial double inversion-recovery
      (DIR) brain magnetic resonance (MR) imaging at 3.0 T can help distinguish the
      primary motor cortex (PMC), or Brodmann area 4, from other selected cortical
      regions, including the primary sensory cortex (PSC), or Brodmann areas 1-3, on
      the basis of the presence of a "triple-layer" appearance. MATERIALS AND METHODS:
      This prospective study was approved by the institutional review board; informed
      consent was obtained from patients. This study included 191 patients (94 female,
      age range, 5-80 years; 97 male, age range, 5-76 years) with normal findings at
      3.0-T MR imaging. The presence or absence of a triple-layer appearance within
      selected cortical regions on DIR images was graded independently by two
      neuroradiologists as definitely present (grade 2), probably present (grade 1), or
      definitely absent (grade 0). Ten additional patients with tumors underwent DIR
      imaging and intraoperative cortical mapping for further validation of the PMC. A
      myelin-stained brain specimen image in a patient not imaged with DIR was
      correlated with a representative set of DIR images. RESULTS: A triple-layer
      appearance was found in the PMC bilaterally in 184 of 191 patients; grade 0 was
      assigned in only seven patients, who were all younger than 10 years. Grades were
      significantly lower in patients younger than 10 years than in others (P < .0001)
      but were not significantly different between older age groups (P > .0018).
      Interobserver agreement was excellent (weighted kappa = 0.843). The PMC
      determined on DIR images was confirmed with cortical mapping in all 10 patients
      with tumors. Triple-layer appearance was not present in the other cortical
      regions examined, including the PSC (P < .01). The triple-layer appearance on DIR
      images corresponded to the myelin band within the PMC present on the myelin
      stained specimen image. CONCLUSION: A triple-layer appearance was found in the
      PMC at thin-section 3.0-T DIR imaging but not in other examined brain regions and
      therefore might be useful as an adjunct sign for identification of motor regions.

PMID- 19098227
TI  - Early Career Achievement Awards: Recognizing achievement of young scholars
      working to foster the discovery, sharing, and application of knowledge concerning
      the responsible use of animals to enhance human life and well-being.

PMID- 19098228
TI  - Effects of different growing diets on performance, carcass characteristics,
      insulin sensitivity, and accretion of intramuscular and subcutaneous adipose
      tissue of feedlot cattle.
AB  - Forty-eight individually fed crossbred steers (British and British x Continental;
      BW=296+/-16.7 kg) were used to evaluate effects of different growing diets on
      changes in accretion of intramuscular (IMF) and subcutaneous (SCF) adipose
      tissues, insulin sensitivity, and carcass traits. Dietary treatments were AL-LC
      (a low-corn diet fed to allow cattle ad libitum access to feed), AL-HC (a high
      corn diet fed to allow cattle ad libitum access to feed), LF-HC (a limit fed high
      corn diet with the energy intake equal to that provided by AL-LC), and AL-IC (a
      diet with approximately the midpoint daily energy intake between AL-LC and AL
      HC). Steers received treatments until d 56, after which all groups were fed AL-HC
      until d 140. Real-time ultrasound and BW measurements were taken every 28 d, and
      3 glucose tolerance tests (GTT) were conducted on d 0, 28, and 56 of the growing
      period to assess insulin sensitivity. Based on ultrasound IMF and SCF readings
      during the growing phase, AL-HC and AL-IC increased accretion of IMF (P=0.01),
      and AL-LC and LF-HC diets resulted in less accretion of SCF (P<0.01) compared
      with other treatments. During the finishing period, accretion of IMF (P=0.13) and
      SCF (P=0.81) did not differ among treatments, which diluted differences in
      overall (d 0 to 140) accretion of IMF (P=0.28) and SCF (P=0.52), such that final
      real-time ultrasound measures of IMF and SCF did not differ (P >or= 0.36) among
      treatments. Actual carcass marbling scores, however, were greater for the AL-HC
      and AL-IC treatments (P=0.02), and 12th-rib fat thickness tended (P=0.08) to be
      greater for AL-HC and AL-IC groups. Based on incremental area under the curve and
      area over the curve as indicators of insulin release and glucose uptake,
      respectively, no differences (P >or= 0.10) in insulin sensitivity were observed
      among treatments. Our results suggest that high-corn diets increase growing phase
      accretion of IMF and SCF; however, these differences were not related to
      differences in glucose and insulin kinetics.

PMID- 19098229
TI  - Genetic associations of sexual precocity with growth traits and visual scores of
      conformation, finishing, and muscling in Nelore cattle.
AB  - The objective of this study was to determine the possible use of heifer pregnancy
      at 16 mo as a selection criterion and its possible genetic associations with hip
      height, yearling weight, and visual scores of conformation, finishing, and
      muscling. The data set contained records of 56,458 Nelore yearlings for the
      traits described above. Covariance components were estimated by bivariate animal
      models assuming a linear model for hip height, yearling weight and conformation,
      and finishing and muscling scores, and a nonlinear (threshold) model for heifer
      pregnancy. Variance components were estimated using Bayesian inference. Flat
      distributions were used for all (co)variance components and genetic correlations.
      The first 5,000 rounds were considered as the burn-in period and discarded. The
      heritability estimate of heifer pregnancy indicates that the trait can be used as
      a selection criterion. Long-term selection for heifer pregnancy will result in a
      reduction of animal height. However, selection for increasing yearling weight
      should be possible in this population of Nelore cattle without having major
      effects on fertility. Selection for increasing visual scores of conformation,
      finishing, and muscling will result in small or no response in heifer pregnancy
      at 16 mo.

PMID- 19098230
TI  - Alkaline hydrolysis of mouse-adapted scrapie for inactivation and disposal of
      prion-positive material.
AB  - Prion diseases such as bovine spongiform encephalopathy, chronic wasting disease,
      and scrapie pose serious risks to human and animal health due to a host of
      disease-specific factors, including the resistance of infectious prions (PrP(Sc))
      to natural degradation and to most commercial inactivation procedures. In an
      attempt to address this concern, a mouse model was used to compare the efficacy
      of an alkaline hydrolysis process with a simulated continuous-flow rendering
      treatment for disposal of PrP(Sc)-infected biological material. Female C57/BL6
      mice (N = 120) were randomly divided into 4 treatment groups (n = 30), and each
      mouse was injected intraperitoneally with their designated treatment inoculum.
      Treatment groups 1 and 2 served as the positive and negative controls,
      respectively. Group 3 was inoculated with rendered scrapie-positive mouse brain
      material to investigate the effectiveness of simulated continuous-flow rendering
      practices to reduce or eliminate PrP(Sc). Group 4 was inoculated with hydrolyzed
      scrapie-positive mouse brain material to determine the sterilizing effect of
      alkaline hydrolysis on PrP(Sc). Mice were monitored for overt signs of disease,
      and those showing clinical signs were killed to prevent undue suffering. Brains
      were obtained from all mice that died (or were killed) and analyzed with an ELISA
      for the presence of PrP(Sc). Results indicated that the simulated continuous-flow
      rendering treatment used for preparing the rendering treatment group inoculum
      failed to completely eliminate PrP(Sc). Rendering delayed, but did not stop,
      clinical mouse-adapted scrapie transmission. Compared with positive controls, the
      rendering treatment group experienced an approximate 45-d average delay in days
      to death (250 vs. 205 d for positive controls; P < 0.0001) and a death loss of
      73.9% (P = 0.0094). Positive controls suffered 100% death loss. The results
      validated the efficacy of the alkaline hydrolysis treatment to inactivate all
      PrP(Sc) because no alkaline hydrolysis treatment group mice succumbed to the
      disease (P < 0.0001). Based on our results, alkaline hydrolysis should be
      considered by the animal rendering and beef packing industries as an alternative
      to incineration, landfill burial, and rendering for disposing of biological
      material potentially infected or contaminated with prion disease.

PMID- 19098231
TI  - The effect of weaner diet protein content and diet quality on the long-term
      performance of pigs to slaughter.
AB  - Short and long-term effects of manipulating dietary CP content and diet quality
      in weaner diets on health and performance of pigs were investigated in a 2 x 2
      factorial combination of CP inclusion (high-CP, 230 g of CP/kg vs. low-CP, 170 g
      of CP/kg) and diet quality (high-quality, cooked cereals, and animal protein vs.
      low-quality, raw cereals, and plant protein). Diets were fed ad libitum for 14 d
      postweaning to pigs weaned at 29.4+/-3.1 d of age and 9.9+/-1.0 kg of BW. From d
      14 to slaughter at 104+/-3 kg, all pigs were fed the same series of standard
      commercial diets. There were 15 replicates per treatment in the weaner phase (<30
      kg) and 5 replicates per treatment in the grower-finisher phase (>30 kg). High
      quality diets promoted gut health as indicated by improved fecal lactobacilli to
      coliform ratio (P=0.002) and decreased fecal enterotoxigenic Escherichia coli
      counts on d 11 postweaning (P=0.028), reducing the risk of postweaning diarrhea
      and improving pig health from weaning to the end of the weaner phase. Reducing CP
      content had no effect on gut health. High-CP (P=0.053) and high-quality (P=0.025)
      diets independently increased ADG during the first 14 d postweaning compared with
      low-CP and low-quality diets, respectively. There were no interactions between
      dietary CP content and quality on any of the response criteria investigated.
      Despite differences in the immediate postweaning period, there was no effect of
      manipulating diet quality or CP content for 2 wk postweaning on lifetime
      performance with pigs reaching slaughter weight in 128+/-7 d. These results
      indicate that high-quality diets may protect pig gut health during the immediate
      postweaning period. However, it may be possible to use less expensive, decreased
      quality weaner diets without any adverse effects on long-term performance when
      weaning older, heavier pigs and where health status, environmental control, and
      stock management are all maintained to a high standard.

PMID- 19098232
TI  - Effects of concentrate replacement by feed blocks on ruminal fermentation and
      microbial growth in goats and single-flow continuous-culture fermenters.
AB  - The effect of replacing concentrate with 2 different feed blocks (FB) on ruminal
      fermentation and microbial growth was evaluated in goats and in single-flow
      continuous-culture fermenters. Diets consisted of alfalfa hay plus concentrate
      and alfalfa hay plus concentrate with 1 of the 2 studied FB. Three trials were
      carried out with 6 rumen-fistulated Granadina goats and 3 incubation runs in 6
      single-flow continuous-culture fermenters. Experimental treatments were assigned
      randomly within each run, with 2 repetitions for each diet. At the end of each in
      vivo trial, the rumen contents were obtained for inoculating the fermenters. For
      each incubation run, the fermenters were inoculated with ruminal fluid from goats
      fed the same diet supplied to the corresponding fermenter flask. The average pH
      values, total and individual VFA, and NH(3)-N concentrations, and
      acetate:propionate ratios in the rumen of goats were not affected (P >or= 0.10)
      by diet, whereas the microbial N flow (MNF) and efficiency were affected (P <or=
      0.001), with the greatest values observed for the diet without FB. In fermenters,
      the diet affected pH (P<0.001), propionate concentrations (P=0.01),
      acetate:propionate ratio (P=0.03), carbohydrate digestibility (P >or= 0.05), and
      total (P=0.02), NH(3) (P=0.005), and non-NH(3) (P=0.02) N flows, whereas the
      efficiency of VFA production was not affected (P=0.75). The effect of diet on MNF
      and efficiency depended on the bacterial pellet used as a reference. An effect
      (P<0.05) of diet on the composition of solid- and liquid-associated bacteria was
      observed. The compositions of liquid-associated bacteria in the fermenter
      contents and effluent were similar (P=0.05). Differences (P<0.001) between in
      vivo and in vitro values for most fermentation variables and bacterial pellet
      compositions were found. Partial replacement of the concentrate with FB did not
      greatly compromise carbohydrate fermentation in unproductive goats. However, this
      was not the case for MNF and efficiency. Differences between the results obtained
      in vivo and in vitro indicate a need to identify conditions in fermenters that
      allow better simulation of fermentation, microbial growth, and bacterial pellet
      composition in vivo. Reduced feeding cost could be achieved with the inclusion of
      FB in the diets of unproductive goats without altering rumen fermentation.

PMID- 19098233
TI  - Investigation of the susceptibility of various strains of mice to
      methyllycaconitine toxicosis.
AB  - Although the mechanism of action for larkspur alkaloids has been described,
      little information is available on the variation of the physiological response of
      individual animals to larkspur alkaloids. Anecdotal observations and pilot
      studies in cattle indicate that there is animal-to-animal variation in response
      to a debilitating dose of larkspur alkaloids. The objective of this study was to
      determine whether there is variation in susceptibility of different strains of
      mice to larkspur alkaloid toxicosis and to identify factors responsible for the
      variation that could then be used as a model for studies in cattle. The acute
      toxicity of methyllycaconitine (MLA) in 9 different inbred strains of mice was
      compared. The rank order, from most to least susceptible, was
      A/J>B10>FVB>BALB/c>C57Bl/6>NZW>C3H>DBA>129. The calculated LD(50) ranged from
      3.3+/-0.2 to 5.8+/-0.8 mg/kg of BW. The toxicokinetic profiles of MLA in the
      susceptible A/J strain and the more resistant 129 strain were compared to
      determine whether their differences in susceptibility were due to differences in
      their ability to eliminate MLA. The differences in toxicokinetic variables
      observed did not explain the differences in susceptibility. The protein
      expression of various nicotinic acetylcholine receptor (nAChR) subunits was also
      compared between the more resistant 129 strain and the susceptible A/J strain.
      The 129 strain of mice had twice the amount of alpha7 nAChR subunit expression as
      the A/J strain, which was in direct proportion to the approximately 2-fold
      difference in LD(50). There was also a significant difference (P<0.05) in
      expression of the alpha3 and alpha5 nAChR subunits between the 129 and A/J
      strains, with the 129 strain having a greater expression in each case. These data
      suggest that the increased susceptibility of the A/J mice could be due to a
      reduced expression of nAChR subunits. Similar analyses need to be made in cattle
      to determine whether there is a difference between breeds in susceptibility to
      larkspur poisoning and to identify the factors that regulate their susceptibility
      to larkspur poisoning. This information would be useful for livestock producers
      in their breeding, culling, and grazing management programs to reduce or prevent
      larkspur poisoning on rangelands.

PMID- 19098234
TI  - Response to dietary digestible energy concentration in growing pigs fed cereal
      grain-based diets.
AB  - Understanding how energy is utilized by the pig, and how the pig responds to
      changes in dietary energy concentration, is essential information in determining
      the optimal concentration of dietary energy under farm conditions, which are
      often highly diverse. The objective of these experiments was to determine how
      changes in dietary DE concentration, achieved through graded changes in diet
      composition, would affect the performance and carcass composition of growing
      pigs. In Exp. 1, which was conducted in a research facility, 300 pigs (31.1 +/-
      2.6 kg) were assigned to diets containing 3.09, 3.24, 3.34, 3.42, or 3.57 Mcal of
      DE/kg. Experiment 2, which was conducted at a commercial swine farm, involved 720
      pigs (36.8 +/- 5.9 kg) assigned to diets containing 3.12, 3.30, or 3.43 Mcal of
      DE/kg. Increased DE concentration was attained by using more wheat, soybean meal,
      and fat and less barley; true ileal lysine was adjusted as DE increased, and
      minimal AA:lysine ratios were maintained. In Exp. 1, ADG improved linearly as the
      energy content of the diet increased (P = 0.03). Feed intake decreased (P <
      0.001) and feed efficiency and daily caloric intake improved (P = 0.005) with
      increased DE content. Variability in growth was not affected by treatment.
      Carcass index and LM thickness were not affected by increasing dietary DE
      content; backfat thickness, however, was increased (P < 0.001). In Exp. 2,
      overall ADG was unaffected by dietary energy content, although an improvement in
      growth was observed until the pigs reached approximately 80 kg of BW. Overall
      feed intake decreased with increasing energy content (P = 0.01), although this
      was not observed during the initial 6 wk of the experiment. Carcass index, lean
      yield, and backfat were not affected by increasing dietary energy content,
      whereas LM thickness tended to increase (P = 0.08). The value per pig was
      unaffected by increasing dietary energy content in both experiments, and returns
      above feed costs were reduced. Increasing the energy density of the diet for
      growing pigs through incremental changes in dietary composition had a variable
      impact on overall growth performance and carcass quality. Increasing the dietary
      DE had no effect on variations in BW at the time of marketing.

PMID- 19098235
TI  - Ideal amino acid balance for sows during gestation and lactation.
AB  - Improving efficiency of protein utilization is important for pregnant sows under
      restricted feed allowance and for lactating sows with limited feed intake. Sows
      have limited ability to support the growth of fetuses and mammary glands during
      late gestation and to support mammary growth and milk production, especially
      during first lactation period. A series of studies was conducted to characterize
      requirements and ideal ratios of AA for 1) fetal growth, 2) mammary gland growth
      of gestating sows, 3) maternal tissue gain of gestating sows, 4) mammary gland
      growth of lactating sows, and 5) maternal tissue gain of lactating sows. A total
      of 97 pregnant sows and their fetuses and a total of 174 lactating sows and their
      nursing piglets were used for these studies to collect fetal tissues, mammary
      tissues, and maternal tissues for AA analysis. Requirements and ideal ratios of
      AA for sows changed dynamically depending on stages of pregnancy. Suggested daily
      requirements for true ileal digestible Lys were 5.57 and 8.78 g, and relative
      ideal ratios for Lys:Thr:Val:Leu (on basis of AA weight) were 100:79:65:88 and
      100:71:66:95 for d 0 to 60 and d 60 to 114 of gestation, respectively.
      Requirements and ideal ratios of AA for lactating sows changed dynamically
      depending on potential amounts of protein mobilization from maternal tissues,
      which are related to voluntary feed intake and milk production. Suggested ideal
      ratios for Lys:Thr:Val:Leu were 100:59:77:115 and 100:69:78:123 if BW losses of
      sows during 21 d of lactation are 0 and 33 to 45 kg, respectively. To optimize
      efficiency of dietary protein utilization by sows, the dietary AA content and
      ratios can be adjusted by stages of pregnancy (i.e., phase feeding) and by
      expected feed intakes or parities of sows during lactation (i.e., parity-split
      feeding) considering the dynamic changes in the requirements and ideal ratios of
      AA.

PMID- 19098236
TI  - Evaluation of corn grain with the genetically modified input trait DAS-59122-7
      fed to growing-finishing pigs.
AB  - A growth performance experiment was conducted to assess the feeding value of a
      double-stacked transgenic corn grain for growing-finishing pigs. The genetically
      modified corn grain contained event DAS-59122-7, which expresses the Cry34/35Ab1
      binary insecticidal protein for the control of corn rootworm. This modified
      transgenic grain is resistant to western corn rootworm and is also tolerant to
      herbicides containing the active ingredient glufosinate-ammonium. The modified
      grain (59122), a nontransgenic near-isoline grain (control corn), and a
      commercial corn (Pioneer brand hybrid 35P12) were grown in a 2005 production
      trial in individually isolated plots that were located 201 m apart. A total of
      108 pigs were allotted to corn-soybean meal diets containing 1 of the 3 grains as
      the sole source of corn. There were 3 pigs per pen and 12 replicate pens per
      treatment. Pigs were fed grower diets from 37 to 60 kg, early finisher diets from
      60 to 90 kg, and late finisher diets from 90 to 127 kg. Within each phase, data
      for ADG, ADFI, and G:F were calculated. At the conclusion of the experiment, pigs
      were slaughtered and data for carcass quality were collected. Differences between
      59122 and the control corn were evaluated, with statistical significance at
      P<0.05. No differences in ADG, ADFI, or G:F between pigs fed the control corn and
      pigs fed the modified corn were observed during the grower, early finisher, or
      late finisher phases. For the entire experimental period, no difference between
      pigs fed the control and the 59122 corn were observed for final BW (128.9 vs.
      127.1 kg), ADG (1.02 vs. 1.00 kg), ADFI (2.88 vs. 2.80 kg), or G:F (0.356 vs.
      0.345 kg/kg). Likewise, no differences in dressing percentage (76.48 vs. 76.30%),
      LM area (49.8 vs. 50.4 cm(2)), 10th-rib back fat (2.20 vs. 2.12 cm), and carcass
      lean content (52.9 vs. 53.4%) were observed between pigs fed the control and the
      59122 corn grain. It was concluded that the nutritional value of the modified
      transgenic corn grain containing event DAS-59122-7 was similar to that of the
      nontransgenic near-isoline control.

PMID- 19098237
TI  - The immunomodulatory effect of lactulose on Enterococcus faecium fed preruminant
      calves.
AB  - Prebiotics and probiotics could represent an effective alternative to the use of
      synthetic antibiotics in nutrition. The mechanisms by which prebiotics affect the
      immune system have not yet been investigated in detail. Most effects have been
      attributed to increases in the innate and acquired immune responses. This study
      was conducted to elucidate the long-term effects of orally administered lactulose
      on the immune response in the intestinal tract of probiotic-fed calves.
      Preruminant calves were randomized to 3 feeding groups: milk replacer containing
      1) no lactulose, 2) 1% lactulose, or 3) 3% lactulose. All 3 milk replacers
      contained 10(9) cfu Enterococcus faecium/kg. Messenger RNA expression of
      different cell activation markers, pro- and antiinflammatory cytokines, and IgA
      Fc receptor was investigated in the ileum, mesenterial lymph node, spleen, and
      white blood cells. A significantly greater number of blood lymphocytes were
      detected in the 3% lactulose group (P = 0.02) than in the control group. The
      expression results in male calves indicated that the transcription of IgA Fc
      receptor in the ileal mucosa of the 1% lactulose treatment group increased
      significantly (P = 0.04) and also tended to increase in the 3% lactulose group (P
      = 0.07). Furthermore, decreases in IL-10 and interferon-gamma mRNA expression
      were observed in the ileum (P = 0.04). The CD4-presenting lymphocytes were
      decreased significantly in the ileum (P = 0.04) and mesenteric lymph node (P =
      0.01), whereas CD8-presenting lymphocytes were increased in the blood (P = 0.03)
      of females. Other proinflammatory cytokines (IL-1beta, IL-8, and tumor necrosis
      factor-alpha) and antiinflammatory cytokines (transforming growth factor-beta1)
      did not show significant differences in mRNA expression among treatment groups.
      The results indicate that additional lactulose feeding had an immunomodulatory
      effect on the composition of T-cell subsets in different immune compartments and
      had minor effects on pro- and antiinflammatory cytokine mRNA expression.

PMID- 19098238
TI  - A model with heterogeneous thresholds for subjective traits: fat cover and
      conformation score in the Pirenaica beef cattle.
AB  - Current selection schemes for livestock improvement use a wide variety of
      phenotypic traits. Some of them, such as sensory, type, or carcass traits, obtain
      their records from subjective grading performed by trained technicians. Data from
      this subjective evaluation usually involve classification under a categorical and
      arbitrary predefined scale, whose output may lead to strong departures from the
      Gaussian distribution. In addition, the scale of grading may be different
      according to different technicians. To study this phenomenon, we have analyzed
      subjective conformation (CON) and fat cover (FAT) scores in the Pirenaica beef
      cattle breed from data provided by 12 different slaughterhouses. Three
      statistical models were used: 1) a Gaussian linear model; 2) an ordered category
      threshold model; and 3) a specific slaughterhouse ordered category threshold
      model. These models were analyzed through a Bayesian analysis via a Gibbs sampler
      with a data augmentation step. Posterior mean estimates of heritability ranged
      from 0.23 to 0.26 for CON, and from 0.13 to 0.16 for FAT. Statistical models were
      compared by the deviance information criteria, and the slaughterhouse-specific
      ordered category threshold model was selected as the most plausible. This result
      was confirmed by the fact that the threshold estimates differed noticeably
      between slaughterhouses. Finally, the proposed model for genetic evaluation
      increased the expected selection response by up to 7.6% for CON and 11.2% for
      FAT.

PMID- 19098239
TI  - Effect of dietary supplementation of n-3 fatty acids and elevated concentrations
      of dietary protein on the performance of sows.
AB  - A study was conducted to determine the effect of dietary supplementation of n-3
      fatty acids (O3FA) with or without elevated concentrations of protein on the
      performance of sows during the first and the subsequent parity. Sixty-four
      pregnant gilts with BW of 195.0 +/- 2.1 kg and backfat (BF) thickness of 12.9 +/-
      0.2 mm were assigned to 4 dietary treatments from d 60 of gestation (late
      gestation) to d 21 of lactation. Dietary treatments were 1) a control diet; 2) a
      high-protein diet (HP); 3) the control diet + 0.2% O3FA (O3); and 4) the HP diet
      + 0.2% O3FA (HPO3). For the control and O3 treatments, CP contents were 12.3% for
      late gestation and 17.9% for lactation, and for the HP and HPO3 treatments, CP
      contents were 18.4% for late gestation and 19.5% for lactation. On d 60 and 110
      of gestation and after farrowing (within 12 h postfarrowing), on d 10 and 21 of
      lactation, BW, BF thickness, and blood samples were obtained. The total number of
      piglets and the number of piglets born alive and their birth weights were
      measured within 12 h postfarrowing. Colostrum and milk samples were obtained on d
      2 and 21 of lactation, respectively. All piglets were weaned at 21 d. The wean-to
      estrus interval and ADFI were recorded. The same measurements were obtained from
      the control and O3 groups during the subsequent parity. Dietary treatment did not
      affect BW, BF thickness, ADFI, and the wean-to-estrus interval of sows during
      their first reproductive cycle. Supplementation of O3FA increased both
      eicosapentaenoic acid and docosahexaenoic acid contents (P < 0.05) in colostrum
      and mature milk. First-parity litter size and piglet birth weight did not differ
      among treatment groups. Piglet BW was greater (P < 0.05) for the O3 group
      compared with both the control and HPO3 groups at d 10 and 21 of lactation. The
      same pattern was also noted for overall piglet BW gain. Both piglet and litter
      characteristics of the HP group did not differ from those of other groups
      throughout lactation. During the subsequent parity, both total and live piglet
      birth weights tended (P < 0.07) to be greater for the O3 group than for the
      control group. Compared with the control group, piglet BW and BW gain in the O3
      group showed a pattern similar to the previous parity. Results indicated that
      O3FA alone during lactation improved the growth of nursing piglets, regardless of
      parity. However, the O3FA diet, with or without elevated protein, did not affect
      first-parity gestation performance, although O3FA alone may have improved piglet
      birth weight in the subsequent litter.

PMID- 19098240
TI  - Modeling methane production from beef cattle using linear and nonlinear
      approaches.
AB  - Canada is committed to reducing its greenhouse gas emissions to 6% below 1990
      amounts between 2008 and 2012, and methane is one of several greenhouse gases
      being targeted for reduction. Methane production from ruminants is one area in
      which the agriculture sector can contribute to reducing our global impact.
      Through mathematical modeling, we can further our understanding of factors that
      control methane production, improve national or global greenhouse gas
      inventories, and investigate mitigation strategies to reduce overall emissions.
      The purpose of this study was to compile an extensive database of methane
      production values measured on beef cattle, and to generate linear and nonlinear
      equations to predict methane production from variables that describe the diet.
      Extant methane prediction equations were also evaluated. The linear equation
      developed with the smallest root mean square prediction error (RMSPE, % observed
      mean) and residual variance (RV) was Eq. I: CH(4), MJ/d=2.72 (+/-0.543) + [0.0937
      (+/-0.0117) x ME intake, MJ/d] + [4.31 (+/-0.215) x Cellulose, kg/d] - [6.49 (+/
      0.800) x Hemicellulose, kg/d] - [7.44 (+/-0.521) x Fat, kg/d] [RMSPE=26.9%, with
      94% of mean square prediction error (MSPE) being random error; RV=1.13].
      Equations based on ratios of one diet variable to another were also generated,
      and Eq. P, CH(4), MJ/d=2.50 (+/-0.649) - [0.367 (+/-0.0191) x (Starch:ADF)] +
      [0.766 (+/-0.116) x DMI, kg/d], resulted in the smallest RMSPE values among these
      equations (RMSPE=28.6%, with 93.6% of MSPE from random error; RV=1.35). Among the
      nonlinear equations developed, Eq. W, CH(4), MJ/d=10.8 (+/-1.45) x (1-e([-0.141
      (+/-0.0381) x DMI, kg/d])), performed well (RMSPE=29.0%, with 93.6% of MSPE from
      random error; RV=3.06), as did Eq. W(3), CH(4), MJ/d=10.8 (+/-1.45) x [1-e({-[
      0.034 x (NFC/NDF)+0.228] x DMI, kg/d})] (RMSPE=28.0%, with 95% of MSPE from
      random error). Extant equations from a previous publication by the authors
      performed comparably with, if not better than in some cases, the newly developed
      equations. Equation selection by users should be based on RV and RMSPE analysis,
      input variables available to the user, and the diet fed, because the equation
      selected must account for divergence from a "normal" diet (e.g., high-concentrate
      diets, high-fat diets).

PMID- 19098241
TI  - Feed intake in the multiparous lactating sow: its relationship with reactivity
      during gestation and tryptophan status.
AB  - Voluntary feed intake in sows after parturition may be related to the capacity of
      the sow to cope with the numerous changes occurring around farrowing. This
      experiment was undertaken to investigate whether the feed intake during lactation
      was related to the reactivity of the sow during gestation and plasma Trp and
      cortisol concentrations. On d 58 of pregnancy, 37 sows were individually placed
      in a novel environment, and their behavior was observed during a 5-min open-field
      test. This test allowed the selection of 12 reactive (R) and 8 nonreactive (NR)
      sows for the study. Sows were fed 3 kg of a standard gestation diet/d before
      farrowing and a standard lactation diet ad libitum thereafter. The behavioral
      reactivity of sows when a human touched their neck in the farrowing crate was
      evaluated on d 72 of gestation, and their behavior during farrowing was analyzed.
      Sows were catheterized on d 70 of gestation, and blood samples were taken after
      an overnight fast on d 37 before farrowing, daily during the week before and the
      week after parturition, and on d 14 and 21 of lactation for plasma Trp and
      cortisol determination. The NR sows were less reactive to human contact (P=0.02),
      had a shorter farrowing duration (P=0.02), and tended to have a shorter birth
      interval between piglets (P=0.09) than the R sows. Feed intake was greater for
      the NR sows than for the R sows during wk 1 of lactation (P=0.02), as well as
      during the whole lactation (P=0.03). Plasma cortisol concentration was maximal on
      the day after farrowing (P=0.01) and returned to basal concentration within 4 d
      postpartum. No relationship was observed between sow behavior and plasma
      concentration of cortisol. For both groups of sows, plasma concentrations of Trp
      between d 2 and 4 postpartum were less than during gestation (P<0.05). The NR
      sows had decreased plasma Trp concentrations compared with the R sows during wk 1
      of lactation (P=0.02). A low reactivity during gestation was associated with
      behavior of the sow that was favorable to piglet survival during farrowing,
      increased feed intake, and decreased plasma Trp concentration during wk 1 of
      lactation. Further research is needed to elucidate whether Trp or Trp metabolites
      are related to reactivity and ADFI of the reproducing sow.

PMID- 19098242
TI  - Backgrounding and finishing diets are associated with inflammatory responses in
      feedlot steers.
AB  - The objective of this investigation was to study the effects of feeding
      backgrounding and finishing diets on selected acute phase proteins in the plasma
      of feedlot steers. Two groups of 12 steers each, at the backgrounding and
      finishing stages, were offered either a backgrounding (45% barley grain-based
      concentrate and 55% barley silage on a DM basis) or a finishing (91% barley grain
      based concentrate and 9% barley silage) diet for 12 and 15 wk, respectively.
      Steers at the backgrounding and finishing stages had initial BW of approximately
      250 and 380 kg, respectively, at the beginning of the experiment. Blood samples
      were obtained from a jugular vein at 3-wk intervals during the experimental
      period beginning at wk 3 or 0 for the backgrounding and finishing periods,
      respectively. Plasma samples were analyzed for serum amyloid A (SAA),
      lipopolysaccharide-binding protein (LBP), haptoglobin, and alpha(1)-acid
      glycoprotein. Steers fed the finishing diet showed peak plasma SAA, LBP, and
      haptoglobin within 3 wk from the initiation of the diet (20, 23, and 1,940
      microg/mL for SAA, LBP, and haptoglobin, respectively). Although plasma alpha(1)
      acid glycoprotein reached a peak concentration (449 microg/mL) at the beginning
      of the finishing phase, no diet effect was obtained for this variable. Steers fed
      the backgrounding diet showed less variation in the concentrations of plasma
      acute phase proteins measured; plasma haptoglobin reached a peak concentration
      (1,720 microg/mL) 9 wk after the beginning of this diet. In conclusion, feeding
      feedlot steers the backgrounding or finishing diet was associated with increased
      peak concentrations of acute phase proteins in the plasma. More research is
      warranted to elucidate the mechanisms behind the inflammatory responses observed
      in feedlot steers and their implications for health issues and the production
      efficiency of feedlot operations.

PMID- 19098243
TI  - Disappearance of nine monoterpenes exposed in vitro to the rumen microflora of
      dairy goats: effects of inoculum source, redox potential, and vancomycin.
AB  - This in vitro study evaluated the roles of diet type and redox potential in the
      degradation of linalool, (E)- and (Z)-beta-ocimene, alpha-phellandrene, (-)-beta
      pinene, (-)-alpha-pinene, (+)-alpha-pinene, sabinene, and alpha-terpinene when
      incubated with rumen microflora, and it provided information on the time course
      of their disappearance. The 9 monoterpenes are found in the winter and spring
      diets of dairy goats in northwestern Mediterranean grazing systems. The diets
      were individually exposed to rumen microflora for 3 h in 17-mL culture tubes at a
      concentration of 4 microL/L. The mixed flora of the inoculum was controlled by
      the use of vancomycin (eliminating gram-positive bacteria) and by the energy
      source (starch vs. structural polysaccharides) on which rumen microflora had been
      grown. Redox potential was controlled by addition of L-cysteine-hydrochloride.
      The preliminary adaptation of microbial inoculum to a diet rich in structural
      carbohydrates reduced the recovery yields of (E)- and (Z)-beta-ocimene, (-)-beta
      pinene, (-)-alpha-pinene, (+)-alpha-pinene, and sabinene (P<0.01), whereas
      vancomycin was without effect. The effect of carbohydrate source likely stems
      from the specific composition of the microbial community rather than from its
      acidogenic capacity. Reducing the culture redox potential by 50 mV reduced the
      recovery yields of linear and monocyclic terpenes (P<0.02), and the culture redox
      potential interacted with the inoculum source for (E)- and (Z)-beta-ocimene and
      for alpha-phellandrene. The time course of terpene disappearance was studied by
      exposing terpenes to a rumen microflora adapted either to starch or to fiber for
      3, 6, or 24 h. The degraded fraction reached a plateau within 3 h for alpha
      phellandrene and for all the isomers of beta-ocimene and pinene with the fiber
      adapted microflora as well as with both inocula for alpha-terpinene. With the
      starch-adapted microflora, this steady state was reached for most other terpenes
      within 6 h of incubation. Sabinene was the only compound still disappearing after
      an incubation period of 6 h. Biotic and environmental variables in the rumen
      affected terpene degradation in a way that can alter the dietary terpene profile
      and possibly its influence on animal product characteristics.

PMID- 19098244
TI  - Effects of different nonionic surfactants on in vitro fermentation
      characteristics of cereal straws.
AB  - The effects of 3 nonionic surfactants (NIS), including alkyl polyglucoside (APG),
      sorbitan trioleate (Span85), and polyoxyethylene sorbitan monostearate (Tween80),
      on in vitro fermentation characteristics of maize stover, rice straw, and wheat
      straw were examined using an in vitro gas production technique. Four levels each
      of APG, Span85, and Tween80 [0, 0.02, 0.05, and 0.1% (vol/vol) of incubation
      solution] were tested in a 4 x 4 x 4 factorial arrangement. The NIS generally
      increased the in vitro maximal gas production (A), but decreased the lag time of
      cereal straws. The effects of NIS on the rate of gas production (B) were related
      to the surfactant type and fermented substrate. The NIS generally increased IVDMD
      and in vitro OM disappearance (IVOMD) of cereal straws, but responses were dose
      dependent. The NIS increased total VFA concentration of in vitro fermentation
      supernatant for maize stover and wheat straw, but decreased total VFA
      concentration for rice straw. The effects of NIS on the molar proportions of
      acetate, propionate, and butyrate were dependent on the dose and type of NIS and
      on fermented substrate. Several interactive effects were noted between or among 3
      surfactants (APG, Span85, and Tween80) on in vitro gas production variables, IVD
      MD, IVOMD, and VFA for each straw; the optimal combinations of 2 or 3 types of
      NIS were determined according to the responses of IVDMD and IVOMD to NIS
      addition. The results of this study suggest that NIS may improve in vitro
      fermentation of low quality roughages and have potential application as feed
      additives in ruminant production.

PMID- 19098245
TI  - Effect of age on the behavioral and physiological responses of piglets to tail
      docking and ear notching.
AB  - Neonatal piglets are often subject to potentially painful processing procedures
      such as tail docking and ear notching during the first few days after birth.
      However, these procedures may influence the development of suckling behavior and
      passive transfer of immunoglobulins, especially if done within the first day
      postpartum. The objective of this experiment was to compare the effects of
      processing piglets during the first 24 h versus at 3 d of age on suckling and
      pain-related behavior, the passive transfer of immunoglobulins, and growth. Six
      piglets per litter from 20 litters (n = 120 piglets) were used in a 3 x 2
      complete block design. Piglets were weighed at birth and assigned to 1 of 3
      treatments (balanced by birth weight): control (unmanipulated), sham processed
      (manually manipulated), and processed (tail docked and ear notched) at 1 of 2
      ages (1 or 3 d of age). Vocalizations were recorded during the procedures, and
      piglets were observed after the procedures for pain-related behavior. Suckling
      behavior was observed for 6 h on each of d 1 to 4. Colostrum samples were
      collected after the birth of all piglets (before first suck), and blood samples
      were collected on d 5 to examine concentrations of immunoglobulins (IgA and IgG)
      and IGF-I. Body weights were measured at birth and on d 5 and 14. During the
      procedures, processed piglets, regardless of age, vocalized at a greater
      frequency (P < 0.001) and produced more high frequency calls (P = 0.016) than
      sham-processed piglets. All piglets on d 1 produced more high frequency calls
      than all piglets on d 3 (P = 0.047). Immediately after the procedures, sham
      processed and processed piglets spent less time lying and more time standing than
      control piglets (P < 0.001), whereas processed piglets jammed their tail between
      their legs more than sham-processed or control piglets (P < 0.001). Lying,
      standing and tail posture were not influenced by age, nor were there age by
      treatment interactions. Piglets on d 1 trembled more than piglets on d 3 (P <
      0.001), and this tended to be exacerbated by processing (P = 0.076). There was no
      effect of treatment or age of treatment on suckling behavior. Processed piglets
      had decreased IgG serum concentrations compared with sham-processed and control
      piglets (P = 0.029), although there was no interaction between treatment and age
      of treatment (P = 0.67). Whereas tail docking and ear notching do appear to
      result in short-term pain and modulated immune status, processing on d 1 appears
      neither better nor worse than processing on d 3.

PMID- 19098246
TI  - Amino acid supplementation of hydrolyzed feather meal diets for finisher pigs.
AB  - The objective of this study was to determine the possibility of replacing soybean
      meal (SBM) in finisher pig diets completely with hydrolyzed feather meal (FM).
      Forty-five gilts and 45 castrated males (57.8+/-0.8 kg of BW; 3 gilts or 3
      castrated males/pen) were randomly assigned to 5 finisher-1 diets with 6 pens per
      diet. At an average pen BW of 81.0+/-1.4 kg, pigs were offered finisher-2 diets.
      Corn-SBM, finisher-1 and finisher-2 positive control (PC) diets were formulated
      to contain 6.1 and 4.7 g of apparent ileal digestible (AID) Lys/kg, respectively.
      Corn-FM negative control (NC) diets were formulated to be iso-N to the PC diets.
      The NC diets were supplemented with Lys and Trp (NRC; NC + Lys and Trp) to
      alleviate apparent deficiencies based on AID AA in FM reported by the 1998 NRC.
      In addition, the NC diets were supplemented further with the third limiting AA,
      Thr (40+3AA; NC + Lys, Trp, and Thr), and fourth and fifth limiting AA, His and
      Ile (40+5AA; NC + Lys, Trp, Thr, His, and Ile), based on the assumption that the
      apparent ileal digestibility of all indispensable AA in FM is 40%. Pigs had ad
      libitum access to feed and water. At the end of the study (112.1+/-1.8 kg), blood
      samples were collected from all pigs before slaughter. As expected, overall ADFI,
      AID Lys (representing indispensable AA) intake (LysI), ADG, and G:F were greater
      and BW gain:LysI (G:LysI) was less in pigs fed the PC diet than those fed the NC
      diet (P<0.001). Pigs fed the NRC diet grew slower than those fed the PC diet
      (P=0.004), and their G:LysI tended to be less than those fed the PC (P=0.083) or
      the 40+3AA and 40+5AA diets (P=0.094). Greater fat-free lean percentage
      (P=0.005), fat-free lean gain (LG; P<0.001), and LG:F (P<0.001) were observed in
      pigs fed the PC diet compared with those fed the NC diet, but their LG:F or
      LG:LysI was similar to those fed the NRC diet. However, LG:F (P=0.030) and
      LG:LysI (P=0.028) were greater in pigs fed the 40+3AA and the 40+5AA diets than
      those fed the NRC diet. Pigs fed the 40+5AA diet tended to utilize AID Lys more
      efficiently for LG than those fed the 40+3AA diet (P=0.068). Subjective meat
      color (P<0.001), firmness (P=0.004), and marbling (P<0.001) scores were greater
      in pigs fed the 40+5AA diet than those fed the 40+3AA diet. Diets seemed to have
      no clear effect on the weight of liver, kidney, and heart or serum urea N and
      triacylglycerides. Pigs fed the PC diet had more serum albumin and total protein
      (P<0.001), but less glucose (P=0.031) and cholesterol (P<0.001) than those fed
      the NC diet. Serum total protein was greater (P=0.031) in pigs fed the 40+5AA
      diet than those fed the 40+3AA diet. The results indicated that the corn-FM diets
      were not as effective as the corn-SBM diet in supporting BW gain of finisher
      pigs. However, the results seemed to indicate that pigs fed the corn-FM diet
      supplemented with the necessary AA can utilize feed and AA for BW gain and lean
      gain as efficiently as those fed the corn-SBM diet. Further research is needed to
      explore fully the optimal AA supplementation strategy to effectively utilize FM
      for pig production.

PMID- 19098247
TI  - Dietary zilpaterol hydrochloride. I. Feedlot performance and carcass traits of
      steers and heifers.
AB  - Experiments were conducted at 3 US locations (CA, ID, and TX) to determine the
      effects of dietary zilpaterol hydrochloride (Zilmax, Intervet Inc., Millsboro,
      DE) and duration of zilpaterol feeding on performance and carcass merit of
      finishing steers and heifers. At each site, 160 steers and 160 heifers were
      stratified within sex by initial BW (study d -1) and assigned randomly within BW
      strata to 1 of 4 treatments in a randomized complete block design (4
      blocks/treatment for each sex). The 4 treatments were arranged in a 2 (no
      zilpaterol vs. zilpaterol) x 2 (20 or 40 d duration of zilpaterol feeding)
      factorial arrangement of treatments. When included in the diet, zilpaterol was
      supplemented at 8.3 mg/kg of DM. Each pen consisted of 10 animals. Each animal
      was individually weighed unshrunk on d 1, 21 or 41, and 66 of the experiment.
      Following d 66, cattle were slaughtered and carcass data collected. Feeding
      zilpaterol increased (P<0.01) final BW of steers and heifers by 11.6 and 6.7 kg,
      respectively. In addition, feeding zilpaterol hydrochloride increased (P <or=
      0.001) ADG 36 and 18%, and increased (P<0.001) G:F 28 and 21% for steers and
      heifers, respectively. For heifers, DMI was decreased (P<0.001) 6.2% when
      zilpaterol was fed, whereas in steers DMI tended (P=0.09) to be decreased 2%. For
      steers and heifers, feeding zilpaterol increased (P<0.001) HCW 16.4 and 12.1 kg,
      dressing percentage 1.5 percentage units for each sex, and LM area 8.23 and 6.37
      cm(2), respectively. Twelfth-rib fat (P >or= 0.12) and KPH (P >or= 0.70) were not
      affected by feeding zilpaterol to steers or heifers. Feeding zilpaterol decreased
      (i.e., improved; P=0.02) calculated yield grade of steer and heifer carcasses.
      Marbling score (P=0.002) and quality grade (P=0.002) were decreased when
      zilpaterol hydrochloride was fed to steers, and the decrease in marbling score
      and quality grade tended to be greater when zilpaterol was fed for 40 compared
      with 20 d (zilpaterol x duration interaction, P=0.07). For heifers, marbling
      score tended (P=0.07) to be decreased and quality grade was decreased (P=0.05)
      when zilpaterol hydrochloride was fed. In general, it appears from these data
      that zilpaterol hydrochloride fed for 20 to 40 d at the end of the finishing
      period enhances growth performance and carcass muscle deposition for steers and
      heifers.

PMID- 19098248
TI  - Behavior and performance of pigs previously housed in large groups.
AB  - A study was conducted to evaluate the effects of social familiarity and initial
      BW variation at mixing on performance and welfare of pigs born to group-housed
      lactating sows. A total of 180 pigs from 24 litters were used in a random design
      with 4 treatments in a 2 x 2 (social familiarity x initial BW uniformity)
      factorial arrangement. Pigs were born in group-farrowing rooms where they mingled
      in large groups of 66 to 80 pigs from 10 d of age. At 8 wk of age (BW=23+/-3.1
      kg), pigs were allocated to 20 pens of 9 pigs (5 castrated males and 4 females)
      in a grow-finish room, with 5 pens assigned to each of 4 treatment combinations
      without consideration of relatedness. Familiar groups consisted of pigs from 1
      farrowing room, and unfamiliar groups consisted of 3 pigs from each of 3
      different farrowing rooms. Uniform BW groups were formed by using the middle 2
      quartiles, and variable BW groups by using the heaviest and lightest quartiles of
      pigs. Aggression and activity behavior were directly observed by scan or
      continuous sampling during a period of 4 h on the first 3 d, d 7, and d 14 after
      grouping. Injury scores were assessed on all pigs immediately before and 48 h
      after grouping. Body weight gain and apparent feed intake were measured every 2
      wk for 14 wk. Aggression in familiar groups was minimal throughout the
      observation periods. Compared with that in familiar groups, total duration of
      fighting was greater in unfamiliar groups on d 0 (upon grouping, 48.5 vs. 0.5+/
      10.88 s/pig(-1).4 h(-1); P<0.001) and on d 1 (10.8 vs. 0.4+/-3.24 s/pig(-1).4 h(
      1); P<0.05) after grouping. Unfamiliar pigs had greater injury scores (6.6 vs.
      1.8+/-0.28; P<0.001) and spent less time eating on d 0 (5.1 vs. 8.8+/-0.92% of
      total observation time; P<0.01) after grouping compared with familiar pigs. The
      ADG and ADFI were decreased in unfamiliar groups during the initial 6 wk, but not
      for the entire 14-wk period in comparison with familiar groups. Body weight
      variation did not affect behavior and performance in familiar groups but
      increased aggression-induced injuries in unfamiliar groups. The results indicated
      that grouping unacquainted pigs derived from large groups induced overt
      aggression, associated injuries and initial reduction in performance, which
      causes welfare concerns on mixing pigs born to group-housed lactating sows.

PMID- 19098249
TI  - Estimation of light lamb carcass composition by in vivo real-time ultrasonography
      at four anatomical locations.
AB  - The objectives of this study were to study the relationship between in vivo
      ultrasound measurements and cold carcass measurements at 4 anatomical points of
      the backbone, and to establish regression equations to estimate carcass
      composition within the cold carcass weight range for Ternasco lambs (8 to 12.5
      kg) by using ultrasonic measurements taken at a single location. Measurements of
      subcutaneous fat and skin thickness and of muscle depth and width were taken over
      the 10th to 11th and 12th to 13th thoracic vertebrae and the 1st to 2nd and 3rd
      to 4th lumbar vertebrae. These measurements were taken at 2 and 4 cm from the
      nearest end of the LM to the backbone and at 1/3 of the LM width with the probe
      perpendicular to and parallel to the backbone. The left sides of the carcasses
      were dissected into muscle, fat, and bone. Body weight (22.6 kg) and cold carcass
      weight (10.8 kg) were representative of Ternasco light lambs. Muscle depth
      measured at 2 cm, 4 cm, and 1/3 of LM width remained regular, with slight ups and
      downs along the spine. All the pairs of in vivo ultrasound and cold carcass
      measurements were significantly different (P<0.05) and had small correlations.
      All the ultrasound measurements of muscle depth at any location or at any
      distance to the backbone were less than their equivalent cold carcass
      measurements, with differences ranging from 0.8 to 5.9 mm. Differences between
      ultrasound fat thickness + interface (US_FDGI) and cold carcass fat thickness
      were less than differences between ultrasound fat thickness and cold carcass fat
      thickness, ranging from -0.9 to -1.0 mm for the former and from -2.1 to -0.5 mm
      for the latter. The small differences in absolute values between US_FDGI and cold
      carcass fat thickness suggest that US_FDGI is the best measure of the real
      fatness level of the lambs. The best prediction equations for muscle, bone, and
      fat were developed with in vivo ultrasound data measured at the 1st to 2nd lumbar
      vertebrae perpendicularly to the backbone, but they had limited predictive value.
      To predict the muscle content of carcass, BW and muscle depth were included, and
      they explained 59% of variation. Fifty-one percent of total fat was predicted by
      BW and fat thickness, whereas only 17% of the variation in bone was predicted by
      2 fat-related variables. The BW of lambs was an important predictor to improve
      regression equations but ultrasound measurements were the most important
      variables when a narrow range of BW was used.

PMID- 19098250
TI  - Differential growth and development of pigs as assessed by X-ray computed
      tomography.
AB  - Data from 54 hybrid (mainly Large White x Landrace) pigs (18 boars, 18 gilts, and
      18 barrows) were used to quantify and mathematically describe the differential
      growth and development of body components of live pigs. The pigs were 32.4 +/-
      3.2 kg of BW and 70 +/- 1 d of age (mean +/- SD) at the beginning of the study,
      were individually penned and fed ad libitum, and were weighed weekly. Computed
      tomography (CT) imaging was used to determine the weights of lean, fat, bone, and
      skin tissue in the live pig at 30, 60, 90, 120, and 150 kg of BW. For each target
      BW, the sum of all the weights of the body components, as assessed by CT, was
      referred to as CT BW. Linear and nonlinear models were developed to evaluate the
      patterns of growth and development of each body component relative to CT BW. The
      correlation between the actual BW and CT BW was close to unity (r = 0.99),
      indicating that CT scanning could accurately predict the BW of pigs. Across sex
      and castrate status, percentage of fat (fat weight/CT BW) in the pig was least
      (11.2%) at the 30-kg target BW and continued to increase to 22.6% by the 150-kg
      target BW. Percentage of lean, however, was greatest (67.2%) at the 30-kg target
      BW and continued to decrease to 53.4% by the 150-kg target BW. The sex or
      castrate status x target BW interaction was significant (P < 0.05) for all the
      body components, indicating that the developmental patterns were different among
      sex or castrate status. Barrows were fatter relative to gilts, which in turn were
      fatter than boars. For lean, the observed pattern for sex or castrate status
      differences was opposite that for fat. To predict responses to management
      strategies on growth and development in pigs, accurate mathematical models are
      required, and the results of this study indicate that the nonlinear (e.g.,
      augmented allometric and generalized nonlinear) functions provided better
      descriptions of the growth and development of most body components of the live
      pig than did the simpler (e.g., linear and allometric) models.

PMID- 19098251
TI  - Urea metabolism in beef steers fed tall fescue, orchardgrass, or gamagrass hays.
AB  - Two experiments were conducted to assess effects of endophyte treatments (Exp.
      1), forage species (Exp. 2), and supplementation (Exp. 2) on urea production,
      excretion, and recycling in beef steers. Infusion of (15,15)N-urea and enrichment
      of urea in urine samples were used to calculate urea-N entry and recycling to the
      gut. Acceptably stable enrichment of (15)N-urea in urine was obtained after 50 h
      of intrajugular infusion of (15,15)N-urea, indicating that valid data on urea
      metabolism can be obtained from steers fed forages twice daily. After adjustment
      by covariance for differences in N intake among treatments in Exp. 1, steers fed
      endophyte-infected tall fescue had less (P<0.10) urea-N entry, recycling to the
      gut, and return of recycled urea-N to the ornithine cycle than those fed
      endophyte-free or novel endophyte-infected tall fescue. However, urea-N urinary
      excretion or return to the gut was similar among endophyte treatments when
      expressed as a proportion of urea-N entry. Urea-N entry and return to the gut in
      Exp. 2 was similar in steers fed gamagrass or orchardgrass hay after adjustment
      by covariance for differences in N intake. Less (P<0.01) urinary excretion,
      expressed as grams per day or as a proportion of urea-N entry, with gamagrass
      than with orchardgrass was associated with faster in vitro NDF-N digestion with
      gamagrass. Supplementation of gamagrass or orchardgrass with 1.76 kg/d of readily
      fermentable fiber and starch decreased urea entry (P<0.06) and urinary excretion
      of urea (P<0.01). Interactions between hay source and supplement reflected a
      greater response to supplementation for steers fed orchardgrass than for those
      fed gamagrass. After adjustment for differences among treatments in N supply,
      results of both experiments support the concept of improved N use in response to
      increased carbohydrate fermentability in the rumen, due either to inherent
      differences in forage fiber or to supplementation with readily fermentable
      carbohydrate (starch or fiber). Closer coordination of ruminal fermentation of
      carbohydrate and N sources provided greater and more efficient capture of dietary
      N as tissue protein in forage-fed steers.

PMID- 19098252
TI  - Enumeration of some cultivable bacterial groups and characterization of some
      abiotic variables in the jejunoileal content of Prim'Holstein veal calves.
AB  - A study was conducted to characterize the bacterial and biochemical composition
      of the jejunoileal content of veal calves and the effect of pre-slaughter fasting
      time. At 22 wk of age, 22 preruminant Prim'Holstein calves fed milk replacer and
      pellets (mainly composed of corn) were slaughtered at 6, 12, or 24 h after their
      last meal. Chyme samples were collected from the jejunoileal compartment just
      after slaughter, and pH and redox potential were immediately measured. Culture
      based methods were used to determine the concentrations of total anaerobic
      microflora, lactate-utilizing bacteria, Bacteroides fragilis group, Lactobacilli,
      Bifidobacteria, Enterococci, and 2 potential pathogenic species, Escherichia coli
      and Clostridium perfringens. Concentrations of l-lactate, ammonia, and short
      chain fatty acids (SCFA) were determined on frozen samples. The biochemical
      composition (DM, total protein, lactose, galactose, glucose, minerals, AA
      profile, and fatty acid profile) of the jejunoileal content was determined only
      on samples from the 6-h fasted group. Microflora concentrations were greater (P <
      0.01) in the 6-h fasted group compared with the 12- and 24-h fasted groups,
      involving a decreased pH (P < 0.05) and greater lactate and SCFA concentrations,
      both linked directly to the fermentative state of the microorganisms. The 6-h
      fasted group showed the least interanimal variability in bacterial group levels,
      except for Cl. perfringens, which presented increased interanimal variability
      regardless of fasting time. At 6 h postprandial, the jejunoileal content of veal
      calves seemed to be in a stable state, allowing the creation of a database on its
      biochemical composition. This study is a key first step in the development of an
      in vitro system for modeling the jejunoileal ecosystem of veal calves. This model
      will provide a useful tool for assessing the effects of feed additives on
      intestinal microflora.

PMID- 19098254
TI  - Effect of feeding reduced crude protein and phosphorus diets on weaning-finishing
      pig growth performance, carcass characteristics, and bone characteristics.
AB  - Two experiments were conducted to determine the effects of feeding a corn- and
      soybean meal-based diet (control) or a low nutrient excretion (LNE) diet,
      formulated with reduced dietary CP and additional synthetic AA, low phytic acid
      corn, and phytase, on pig growth performance during the grower (BW=32 to 77 kg)
      and finisher (BW=78 to 126 kg) periods and on carcass and bone characteristics at
      slaughter. Pigs (32+/-1.3 kg of BW, Exp. 1; 6.7+/-0.27 kg of BW, Exp. 2) were
      blocked by sex and BW and randomly allotted to a control or LNE diet. Pigs were
      housed in 4 rooms during the nursery period and in 2 rooms during the grower and
      finisher periods, with individual and identical ventilation systems. Pigs were
      phase fed 3 nursery diets for 5 wk (Exp. 2) and phase fed 2 grower and 2 finisher
      diets for 16 wk (Exp. 1 and 2). Pigs were housed 4 or 5 pigs/pen with 9 pens x
      sex(-1) x treatment(-1) during the nursery period and 4 or 5 pigs/pen with 5 pens
      x sex(-1) x treatment(-1) in the grower phase and 2 or 3 pigs/pen in the finisher
      phase. Individual BW and pen feed disappearance were recorded weekly in the
      nursery period and every 2 wk in the grower-finisher period. Pigs were scanned
      ultrasonically at d 34 of the nursery period and wk 8 and 16 of the grower
      finisher period to determine backfat depths and LM area. Ten pigs x sex(-1) x
      treatment(-1) were slaughtered at wk 16 of each experiment to determine carcass
      characteristics. Overall growth performance was not different during each
      experiment. However, nursery G:F (control=0.65; LNE=0.60), grower ADG (Exp. 1 and
      2), and grower G:F (Exp. 2) were reduced (P<0.05) when the LNE diets were fed.
      Diet had no effect on 10th-rib carcass data in either experiment. Metatarsal bone
      ash percentage was reduced (P<0.05) when the LNE diets were consumed in both
      experiments. Feeding LNE diets resulted in the maintenance of overall growth
      performance, bone variables, and carcass characteristics. However, further
      refinements are still required in the nursery and grower phases of pig production
      to optimize LNE diet use by the swine industry.

PMID- 19098253
TI  - Effects of growth hormone-releasing hormone treatment on milk production and
      plasma hormones and metabolites in lactating Japanese Black cows under negative
      energy balance.
AB  - The current study was performed to clarify the effects of GHRH treatment on milk
      production and plasma hormones and metabolites in lactating Japanese Black cows
      (a beef breed) under negative energy balance (EB). Ten multiparous lactating beef
      cows were offered a normal-energy diet daily (110% of ME requirements for
      maintenance and lactation) until 5 d in milk (DIM) to standardize the cows before
      dietary treatment. From 6 DIM to the final days (63 DIM) of the experiment, the
      cows were allotted to experimental dietary treatments: 5 cows were offered a diet
      formulated for 130% [high-energy diet (HED)] and the remaining 5 cows were
      offered a diet formulated for 80% [low-energy diet (LED)] of ME requirements for
      maintenance and lactation. In addition, all cows received daily subcutaneous
      injections of 3 mg of bovine GHRH from 36 to 56 DIM (GHRH treatment period).
      Differences in BW of HED- and LED-fed cows at 63 DIM were +28.4 and -7.2 kg
      compared with BW at 6 DIM, and HED- and LED-fed cows were under positive EB
      (+23.7 MJ/d) and negative EB (-11.6 MJ/d) throughout the experiment period.
      Treatment with GHRH increased (P<0.01) the average daily milk yield to 6.2 kg in
      HED-fed cows compared with a milk yield of 5.3 kg for 7 d before the GHRH
      treatment period (pretreatment period); LED-fed cows had no increase in milk
      production from GHRH treatment. Plasma GH, IGF-1, insulin, and glucose
      concentrations increased (P<0.05) after GHRH treatment in both HED- and LED-fed
      cows; GHRH treatment also induced an increase (P<0.05) in the net area under the
      curve of plasma insulin after glucose challenge in both HED- and LED-fed cows.
      Plasma urea N concentrations were decreased (P<0.05) by GHRH treatment in HED-fed
      cows, but not in LED-fed cows. Plasma NEFA concentration was unaffected by GHRH
      treatment in both HED- and LED-fed cows. We conclude that GHRH treatment of
      lactating Japanese Black cows stimulates endogenous GH and subsequent IGF-1
      secretion and might induce an increase in insulin resistance, irrespective of EB;
      however, compared with lactating dairy cows, both galactopoietic and lipolytic
      effects of GHRH might be insufficiently exerted under negative EB in lactating
      beef cows.

PMID- 19098255
TI  - Genetic variability of the Gentile di Puglia sheep breed based on microsatellite
      polymorphism.
AB  - The aim of the present study was to estimate the genetic variability of the
      Gentile di Puglia sheep breed by using microsatellite markers, to provide
      information useful for conservation. The DNA of 82 animals, belonging to 6
      different farms, was analyzed at 19 microsatellite loci. The number of alleles,
      allele frequencies, deviations from Hardy-Weinberg proportions, linkage
      disequilibrium among loci, genetic similarity, genetic distances, and molecular
      coancestry-based parameters were calculated. Seventeen out of 19 microsatellites
      showed heterozygote deficiency in the whole population, although only 4
      (OarAE129, ILSTS28, ILSTS5, MAF33) showed significant deviations from Hardy
      Weinberg proportions (P<0.01). The genetic similarity (an index of allele sharing
      among individuals) within the whole population was low (0.318), and the average
      number of alleles per locus was quite high (9.68). The results obtained
      highlighted a population presenting both a deficiency of heterozygotes and great
      genetic variability. These results suggest that stratification of the breed in
      subpopulations, probably derived from different farm management in each herd, led
      to a population characterized by great genetic diversity among different herds
      and by great similarity within each herd. Moreover, in the past, Gentile di
      Puglia sheep have undergone a strong numeric decline, involving genetic drift
      effects and considerable consanguinity within the breed.

PMID- 19098256
TI  - What motivates nonconformity? Uniqueness seeking blocks majority influence.
AB  - A high need for uniqueness undermines majority influence. Need for uniqueness (a)
      is a psychological state in which individuals feel indistinguishable from others
      and (b) motivates compensatory acts to reestablish a sense of uniqueness. Three
      studies demonstrate that a strive for uniqueness motivates individuals to resist
      majority influence. In Study 1, the need for uniqueness was measured, and it was
      found that individuals high in need for uniqueness yielded less to majority
      influence than those low in need for uniqueness. In Study 2, participants who
      received personality feedback undermining their feeling of uniqueness agreed less
      with a majority (vs. minority) position. Study 3 replicated this effect and
      additionally demonstrated the motivational nature of the assumed mechanism: An
      alternative means that allowed participants to regain a feeling of uniqueness
      canceled out the effect of high need for uniqueness on majority influence.

PMID- 19098257
TI  - Self-categorization with a novel mixed-race group moderates automatic social and
      racial biases.
AB  - People perceive and evaluate others according to social categories. Yet social
      perception is complicated by the fact that people have multiple social
      identities, and self-categorization with these identities shifts from one
      situation to another. Two experiments examined whether self-categorization with a
      novel mixed-race group would override automatic racial bias. Participants
      assigned to a mixed-race group had more positive automatic evaluations of Black
      ingroup than Black outgroup members. Comparing these evaluations to Black and
      White faces unaffiliated with either group indicated this preference was driven
      by ingroup bias rather than outgroup derogation. Moreover, both outgroup and
      unaffiliated faces elicited automatic racial bias (White > Black), suggesting
      that automatic evaluations are sensitive to both the current intergroup context
      (positive evaluations of novel ingroup members) and race (racial bias toward
      outgroup and unaffiliated faces). These experiments provide evidence that self
      categorization can override automatic racial bias and that automatic evaluations
      shift between and within social contexts.

PMID- 19098258
TI  - Is the pain worth the gain? The advantages and liabilities of agreeing with
      socially distinct newcomers.
AB  - The impact of diversity on group functioning is multifaceted. Exploring the
      impact of having a newcomer join a group, the authors conducted a 2 (social
      similarity of newcomer to oldtimers; in-group or out-group) x 3 (opinion
      agreement: newcomer has no opinion ally, one opinion ally, or two opinion allies)
      interacting group experiment with four-person groups. Groups with out-group
      newcomers (i.e., diverse groups) reported less confidence in their performance
      and perceived their interactions as less effective, yet they performed better
      than groups with in-group newcomers (i.e., homogeneous groups). Moreover,
      performance gains were not due to newcomers bringing new ideas to the group
      discussion. Instead, the results demonstrate that the mere presence of socially
      distinct newcomers and the social concerns their presence stimulates among
      oldtimers motivates behavior that can convert affective pains into cognitive
      gains.

PMID- 19098259
TI  - What we regret most are lost opportunities: a theory of regret intensity.
AB  - A recent theory (Roese & Summerville, 2005) has suggested that regret is
      intensified by perceptions of future opportunity. In this work, however, it is
      proposed that feelings of regret are more likely elicited by perceptions of lost
      opportunity: People regret outcomes that could have been changed in the past but
      can no longer be changed and for which people experience low psychological
      closure. Consistent with the lost opportunity principle, Study 1 revealed that
      regretted experiences in the most commonly regretted life domains are perceived
      as offering the least opportunity for improvement in the future, Study 2
      indicated that people experience the most regret for outcomes that are not
      repeatable, and Study 3 revealed that perceptions of higher past than future
      opportunities and low psychological closure predict regret intensity. Discussion
      focuses on the hope-inducing yet ephemeral nature of perceived future opportunity
      and on the relationship between dissonance reduction and closure.

PMID- 19098260
TI  - Lessons learned and challenges in building a Filipino health coalition.
AB  - In recent years, community-based coalitions have become an effective channel to
      addressing various health problems within specific ethnic communities. The
      purpose of this article is twofold: (a) to describe the process involved in
      building the Kalusugan Coalition (KC), a Filipino American health coalition based
      in New York City, and (b) to highlight the lessons learned and the challenges
      from this collaborative venture. The challenges described also offer insights on
      how the coalition development process can be greatly affected by the partnership
      with an academic institution on a community-based research project. Because each
      cultural group has unique issues and concerns, the theoretical framework used by
      KC offers creative alternatives to address some of the challenges regarding
      coalition infrastructures, leadership development, unexpected change of coalition
      dynamics, and cultural nuances.

PMID- 19098261
TI  - Understanding the data-action cycle of surveillance: a qualitative study of
      federal and state stakeholders.
AB  - This qualitative study aims to understand how personnel in state and federal
      agencies view surveillance systems and the extent to which systematically
      collected data inform nutrition and physical activity policies and interventions
      addressing obesity. In-depth interviews were conducted with 17 respondents
      purposively sampled from state health departments, federal public health
      agencies, and prevention research centers. All informants acknowledged the
      importance of surveillance systems and influence of the data-action cycle for
      monitoring trends and increasing obesity awareness. However, state-level
      respondents believed surveillance systems should be designed for programmatic
      purposes, whereas federal participants thought they should be designed for
      monitoring. Respondents held differing opinions about the flexibility,
      timeliness, accessibility, and usefulness of existing national surveillance
      systems, highlighting significant differences in state and federal agencies'
      perceptions and utilization of surveillance systems. Such discrepancies call for
      increased communication surrounding purposes and uses of surveillance data,
      enabling stronger partnerships between state and federal agencies.

PMID- 19098262
TI  - A case study in teaching tobacco policy advocacy at a Historically Black
      university.
AB  - Policy advocacy is increasingly recognized as a crucial component of the training
      provided to health educators but relatively few universities offer advocacy
      training as part of their professional preparation programs for health educators.
      Historically Black colleges and universities (HBCUs) represent a natural setting
      for creating strong Black leaders in tobacco policy advocacy. This case study
      focuses on experiential education at an HBCU to develop advocacy skills around
      tobacco issues among Black college students. The authors describe the structure
      and content of two tobacco policy courses, their efforts to evaluate these
      courses, and the lessons they learned planning and conducting them. They believe
      their experience can prove useful to others developing curricula for teaching
      policy advocacy skills to health education students.

PMID- 19098263
TI  - Using the internet to educate adolescents about osteoporosis: application of a
      tailored web-education system.
AB  - Osteoporosis is a "pediatric disease with geriatric consequences." This article
      describes the development and pilot testing of an online system to educate high
      school students grades 9-12 about osteoporosis; an age where positive health
      changes could have long lasting effects. The intervention goal was to improve
      knowledge about osteoporosis and intent to adopt healthy bone practices. Online
      pre- and postintervention surveys evaluated participants' pre- and
      postintervention osteoporosis knowledge, attitudes, preventive practices, and
      postintervention intent to change healthy bone practices. Participants completed
      the Web-based program that provided detailed information about osteoporosis, and
      healthy bone practices, immediately after completing the pretest and just prior
      to completing the posttest. Eighty-nine students completed both the pre/posttests
      and were included in data analysis. Participants ranged in age from 13 to 17 and
      75% were Caucasian (n = 65). Based on pre/posttest scores of 9 factual questions,
      students significantly improved their knowledge (p < .0001) and overall knowledge
      rating about osteoporosis at posttest (p < .001). Participants changed their
      perception regarding the disease's seriousness (p < .001), and considered
      adopting osteoporosis prevention practices. The study shows that an interactive
      educational Web site is an effective method for increasing awareness and
      understanding of osteoporosis in high school students.

PMID- 19098264
TI  - Hidden heroines: lone mothers assessing community health using photovoice.
AB  - Between 2005 and 2007, a small group of lone mothers in Moncton, New Brunswick,
      carried out participatory action research within a university-community agency
      partnership. Applying the method of photovoice, the women took pictures within
      their community context on topics that they considered important to their health,
      health promotion, and quality of life. Eight themes that emerged from the process
      were represented with pictures and captions and presented in numerous public
      venues and conferences. Themes included finances, stress, support, personal
      development, violence and abuse, place, and transportation. The visual images and
      accompanying captions bring to the public arena the voices of those who are often
      most affected by public policy but have little, if any, input into its creation.
      Nurses and other health professionals can play a critical role in working toward
      gender and economic justice, while accompanying marginalized populations in ways
      that respect their beliefs, perceptions, and experiences.

PMID- 19098265
TI  - Design elements for the development of cancer education print materials for a
      Latina/o audience.
AB  - Health educators can help reduce cancer disparities in Latino populations through
      the creation of effective print materials. In this effort, the National Cancer
      Institute conducted a comprehensive needs assessment to identify key design
      elements of cancer education programs and create a cost-effective process that
      would ensure consistency in the development of materials. This article introduces
      the Checklist of Design Elements for the Development of Cancer Education Print
      Materials for Latina/o Audiences (CEMLA), which includes a total of 10 design
      elements related to the process of developing materials and content. Using social
      learning theory as a theoretical framework, design elements are included that
      reflect cultural sensitivity at the surface and deep structure levels. This is
      the most comprehensive effort to date to integrate and synthesize theory and
      application in the design of materials for this audience.

PMID- 19098266
TI  - Confronting the diabetes disparity: a look at diabetes, nutrition, and physical
      activity programs in the Lower Rio Grande Valley.
AB  - Diabetes prevalence is higher along U.S.-Mexico border than in nonborder regions,
      and numerous community-based organizations are addressing this diabetes disparity
      through prevention and management programs. However, the nature, scope, and
      effectiveness of these efforts and programs are not well documented. This study
      aims at identifying key characteristics of diabetes programs in a Texas-Mexico
      border region with a predominately Hispanic, underserved population. A survey is
      administered to 84 community-based organizations in the Lower Rio Grande Valley
      (LRGV); 25 organizations respond. Nineteen programs related to diabetes and
      healthy lifestyle behaviors are identified in the LRGV. The majority of the
      programs are based on guidelines of national and state professional associations
      and agencies; target low-income and minority populations; are offered at no cost;
      and include program evaluation activities. Future research should examine the
      effectiveness, as well as the fidelity of the guidelines, of diabetes programs in
      the border region.

PMID- 19098267
TI  - Culturally specific dance to reduce obesity in African American women.
AB  - This article provides evidence of a culturally specific dance intervention to
      decrease obesity as measured by body fat and body mass index (BMI) in African
      American women. A community partnership was formed with two African American
      churches to develop an intervention to address the issue of obesity. The
      culturally specific dance intervention was delivered two times per week for 8
      weeks, choreographed to gospel music selected by the experimental group
      participants, and taught by an African American woman. Body fat and BMI were
      assessed at three time points and revealed significant differences between the
      two groups. Attending a minimum of 7 classes was enough to show an observed dose
      effect and the intervention was found to be culturally specific by understanding
      their roles as African American women. This community partnership was an
      effective way to promote a church-based, culturally specific dance intervention
      to improve the health of African American women.

PMID- 19098268
TI  - Dynamic evolution of oryza genomes.

PMID- 19098269
TI  - Dynamic evolution of oryza genomes is revealed by comparative genomic analysis of
      a genus-wide vertical data set.
AB  - Oryza (23 species; 10 genome types) contains the world's most important food crop
      - rice. Although the rice genome serves as an essential tool for biological
      research, little is known about the evolution of the other Oryza genome types.
      They contain a historical record of genomic changes that led to diversification
      of this genus around the world as well as an untapped reservoir of agriculturally
      important traits. To investigate the evolution of the collective Oryza genome, we
      sequenced and compared nine orthologous genomic regions encompassing the Adh1
      Adh2 genes (from six diploid genome types) with the rice reference sequence. Our
      analysis revealed the architectural complexities and dynamic evolution of this
      region that have occurred over the past approximately 15 million years. Of the 46
      intact genes and four pseudogenes in the japonica genome, 38 (76%) fell into
      eight multigene families. Analysis of the evolutionary history of each family
      revealed independent and lineage-specific gain and loss of gene family members as
      frequent causes of synteny disruption. Transposable elements were shown to
      mediate massive replacement of intergenic space (>95%), gene disruption, and
      gene/gene fragment movement. Three cases of long-range structural variation
      (inversions/deletions) spanning several hundred kilobases were identified that
      contributed significantly to genome diversification.

PMID- 19098270
TI  - Characterization of Raphanus sativus pentatricopeptide repeat proteins encoded by
      the fertility restorer locus for Ogura cytoplasmic male sterility.
AB  - Cytoplasmic male sterility is a maternally inherited trait in higher plants that
      prevents the production of functional pollen. Ogura cytoplasmic male sterility in
      radish (Raphanus sativus) is regulated by the orf138 mitochondrial locus. Male
      fertility can be restored when orf138 accumulation is suppressed by the nuclear
      Rfo locus, which consists of three genes putatively encoding highly similar
      pentatricopeptide repeat proteins (PPR-A, -B, and -C). We produced transgenic
      rapeseed (Brassica napus) plants separately expressing PPR-A and PPR-B and
      demonstrated that both encoded proteins accumulated preferentially in the anthers
      of young flower buds. Immunodetection of ORF138 showed that, unlike PPR-B, PPR-A
      had no effect on the synthesis of the sterility protein. Moreover,
      immunolocalization experiments indicated that complete elimination of ORF138 from
      the tapetum of anthers correlated with the restoration of fertility. Thus, the
      primary role of PPR-B in restoring fertility is to inhibit ORF138 synthesis in
      the tapetum of young anthers. In situ hybridization experiments confirmed, at the
      cellular level, that PPR-B has no effect on the accumulation of orf138 mRNA.
      Lastly, immunoprecipitation experiments demonstrated that PPR-B, but not PPR-A,
      is associated with the orf138 RNA in vivo, linking restoration activity with the
      ability to directly or indirectly interact with the orf138 RNA. Together, our
      data support a role for PPR-B in the translational regulation of orf138 mRNA.

PMID- 19098271
TI  - ATM-ATR-dependent up-regulation of DNAM-1 and NKG2D ligands on multiple myeloma
      cells by therapeutic agents results in enhanced NK-cell susceptibility and is
      associated with a senescent phenotype.
AB  - There is much evidence to support a role for natural killer (NK) cells in
      controlling the progression of multiple myeloma (MM), a malignancy characterized
      by an abnormal plasma cell proliferation in the bone marrow (BM). Induction of
      DNA damage response has been recently shown capable of enhancing NKG2D ligand
      (NKG2DL) expression, but nothing is known about DNAM-1 ligand (DNAM-1L)
      regulation. In this study, we show that myeloma cells treated with low doses of
      therapeutic agents commonly used in the management of patients with MM, such as
      doxorubicin, melphalan, and bortezomib, up-regulate DNAM-1 and NKG2D ligands.
      Accordingly, therapeutic drug treatment of MM cells increases NK-cell
      degranulation, the NKG2D and DNAM-1 receptors being the major triggering
      molecules. Similar data were also obtained using ex vivo primary plasma cells
      derived from MM patients. Drug-induced DNAM-1 and NKG2D ligand expression was
      abolished after treatment with the ATM (ataxia telangiectasia mutated) and ATR
      (ATM- and RAD3-related) pharmacologic inhibitors caffeine and KU-55933, and was
      preferentially associated with senescent cells arrested in the G2 phase of the
      cell cycle. Altogether, our findings have identified a common pathway that can
      trigger the up-regulation of different NK cell-activating ligands and suggest
      that NK cells represent an immunosurveillance mechanism toward cells undergoing
      stress-induced senescent programs.

PMID- 19098272
TI  - Identification of a particular HIV-specific CD8+ T-cell subset with a CD27+
      CD45RO-/RA+ phenotype and memory characteristics after initiation of HAART during
      acute primary HIV infection.
AB  - CD8(+) T cells play an important role in controlling viral infections. Defective
      CD8(+) T-cell responses during HIV infection could contribute to viral
      persistence. Early initiation of highly active antiretroviral therapy during
      acute primary HIV infection helps to preserve HIV-specific immune responses.
      Here, we describe a particular CD27(+) CD45RO(-)/RA(+) HIV-specific CD8(+) T cell
      in participants treated early during the primary infection. These cells, which
      were present at a very low frequency during primary HIV infection, increased
      markedly after early treatment, whereas their frequency remained unchanged in
      untreated participants and in participants treated later. These nonnaive antigen
      experienced cells are in a resting state and have characteristics of long-lived
      memory cells. They also possess direct effector capabilities, such as cytokine
      production, and are able to proliferate and to acquire cytotoxic functions on
      reactivation. Our results suggest that these HIV-specific CD27(+) CD45RO(-)/RA(+)
      CD8(+) T cells, observed when early viral replication is inhibited, form a pool
      of resting cells with memory characteristics.

PMID- 19098273
TI  - Toll-like receptor 4 in lymphatic endothelial cells contributes to LPS-induced
      lymphangiogenesis by chemotactic recruitment of macrophages.
AB  - The lymphatic vessel is a major conduit for immune cell transport; however,
      little is known about how lymphatic vessels regulate immune cell trafficking and
      how lymphatic vessels themselves respond to inflammation. Toll-like receptor 4
      (TLR4) plays a central role in lipopolysaccharide (LPS)-induced inflammation, but
      the role of TLR4 in lymphatic endothelial cells (LECs) is poorly understood.
      Here, we found that LECs express high amounts of TLR4 in the intracellular
      region, and that the TLR4 of LECs is the main mediator of nuclear factor-kappaB
      (NF-kappaB) activation by LPS. LPS-TLR4 signaling in LECs resulted in the
      production of various chemokines for chemotaxis of macrophage. In addition, TLR4
      in LECs actively contributed to the recruitment of macrophages to the draining
      lymphatic vessel. Furthermore, the macrophages that infiltrated into the
      lymphatic vessel induced lymphangiogenesis by secreting lymphangiogenic growth
      factors. These phenomena were largely attenuated not only in the mice defective
      in TLR4 signaling but also in the chimeric mice defective in TLR4 signaling that
      were recipients for bone marrow transplantation from normal TLR4-signaling mice.
      In conclusion, TLR4 in LECs plays an essential role in LPS-induced inflammatory
      lymphangiogenesis by chemotactic recruitment of macrophages.

PMID- 19098274
TI  - Floor effects associated with universal screening and their impact on the early
      identification of reading disabilities.
AB  - Response to intervention (RTI) holds great promise for the early identification
      and prevention of reading disabilities. The success of RTI rests in part on the
      accuracy of universal screening tools used within this framework. Despite
      advancements, screening instruments designed to identify children at risk for
      reading disabilities continue to have limited predictive validity. In this study,
      the authors examined a common screening instrument for the presence of floor
      effects and investigated the impact that these effects have on the predictive
      validity of the instrument. Longitudinal data (kindergarten to third grade) from
      a large cohort of children were used. These data included children's performance
      on five measures from the Dynamic Indicators of Basic Early Literacy Skills
      (DIBELS) and two reading achievement outcome measures. The results showed that
      DIBELS measures were characterized by floor effects in their initial
      administrations and that these effects reduced the predictive validity of the
      measures. The implications of these findings for early identification are
      discussed.

PMID- 19098275
TI  - Manganese tissue dosimetry in rats and monkeys: accounting for dietary and
      inhaled Mn with physiologically based pharmacokinetic modeling.
AB  - Manganese (Mn) is an essential nutrient required for normal tissue growth and
      function. Following exposures to high concentrations of inhaled Mn, there is
      preferential accumulation of Mn in certain brain regions such as the striatum and
      globus pallidus. The goal of this research was to complete a physiologically
      based pharmacokinetic (PBPK) model for Mn in rats and scale the model to describe
      Mn tissue accumulation in nonhuman primates exposed to Mn by inhalation and diet.
      The model structure includes saturable tissue binding with association and
      dissociation rate constants, asymmetric tissue permeation flux rate constants to
      specific tissues, and inducible biliary excretion. The rat PBPK model described
      tissue time-course studies for various dietary Mn intakes and accounted for
      inhalation studies of both 14-day and 90-day duration. In monkeys, model
      parameters were first calibrated using steady-state tissue Mn concentrations from
      rhesus monkeys fed a diet containing 133 ppm Mn. The model was then applied to
      simulate 65 exposure days of weekly (6 h/day; 5 days/week) inhalation exposures
      to soluble MnSO(4) at 0.03 to 1.5 mg Mn/m(3). Sensitivity analysis showed that Mn
      tissue concentrations in the models have dose-dependencies in (1) biliary
      excretion of free Mn from liver, (2) saturable tissue binding in all tissues, and
      (3) differential influx/efflux rates for tissues that preferentially accumulate
      Mn. This multispecies PBPK model is consistent with the available experimental
      kinetic data, indicating preferential increases in some brain regions with
      exposures above 0.2 mg/m(3) and fairly rapid return to steady-state levels
      (within several weeks rather than months) after cessation of exposure. PBPK
      models that account for preferential Mn tissue accumulation from both oral and
      inhalation exposures will be essential to support tissue dosimetry-based human
      risk assessments for Mn.

PMID- 19098276
TI  - Acute perchloroethylene exposure alters rat visual-evoked potentials in relation
      to brain concentrations.
AB  - These experiments sought to establish a dose-effect relationship between the
      concentration of perchloroethylene (PCE) in brain tissue and concurrent changes
      in visual function. A physiologically based pharmacokinetic (PBPK) model was
      implemented to predict concentrations of PCE in the brains of adult Long-Evans
      rats following inhalation exposure. The model was evaluated for performance
      against tissue concentrations from exposed rats (n = 40) and data from the
      published scientific literature. Visual function was assessed using steady-state
      pattern-elicited visual-evoked potentials (VEPs) recorded from rats during
      exposure to air or PCE in two experiments (total n = 84) with concentrations of
      PCE ranging from 250 to 4000 ppm. VEP waveforms were submitted to a spectral
      analysis in which the major response component, F2, occurring at twice the visual
      stimulation rate, was reduced in amplitude by PCE exposure. The F2 amplitudes
      were transformed to an effect-magnitude scale ranging from 0 (no effect) to 1
      (maximum possible effect), and a logistical function was fit to the transformed
      values as a function of estimated concurrent brain PCE concentrations. The
      resultant function described a dose-response relationship between brain PCE
      concentration and changes in visual function with an ED(10) value of
      approximately 0.684 mg/l and an ED(50) value of approximately 46.5 mg/l. The
      results confirmed that visual function was disrupted by acute exposure to PCE,
      and the PBPK model and logistic model together could be used to make quantitative
      estimates of the magnitude of deficit to be expected for any given inhalation
      exposure scenario.

PMID- 19098279
TI  - Neonatal death in mice lacking cardiotrophin-like cytokine is associated with
      multifocal neuronal hypoplasia.
AB  - Mice with null mutations of ciliary neurotrophic factor (Cntf) receptor alpha
      (Cntf-Ralpha), or cytokine-like factor 1 (Clf), one component of Cntf-II (a
      heterodimeric Cntf-Ralpha ligand), die as neonates from motor neuron loss
      affecting the facial nucleus and ventral horn of the lumbar spinal cord. Exposure
      to cardiotrophin-like cytokine (Clc), the other putative Cntf-II element,
      supports motor neuron survival in vitro and in ovo. Confirmation that Clc
      ablation induces an equivalent phenotype to Clf deletion would support a role for
      Clc in the functional Cntf-II complex. In this study, Clc knockout mice had
      decreased facial motility, did not suckle, died within 24 hours, and had 32% and
      29% fewer motor neurons in the facial nucleus and lumbar ventral horn,
      respectively; thus, Clc is essential for motor neuron survival during
      development. The concordance of the Clc knockout phenotype with those of mice
      lacking Cntf-Ralpha or Clf bolsters the hypothesis that Clc participates in Cntf
      II.

PMID- 19098277
TI  - Identification of replication-competent HSV-1 Cgal+ strain signaling targets in
      human hepatoma cells by functional organelle proteomics.
AB  - In the present work, we have attempted a comprehensive analysis of cytosolic and
      microsomal proteomes to elucidate the signaling pathways impaired in human
      hepatoma (Huh7) cells upon herpes simplex virus type 1 (HSV-1; Cgal(+))
      infection. Using a combination of differential in-gel electrophoresis and nano
      liquid chromatography/tandem mass spectrometry, 18 spots corresponding to 16
      unique deregulated cellular proteins were unambiguously identified, which were
      involved in the regulation of essential processes such as apoptosis, mRNA
      processing, cellular structure and integrity, signal transduction, and
      endoplasmic-reticulum-associated degradation pathway. Based on our proteomic data
      and additional functional studies target proteins were identified indicating a
      late activation of apoptotic pathways in Huh7 cells upon HSV-1 Cgal(+) infection.
      Additionally to changes on RuvB-like 2 and Bif-1, down-regulation of Erlin-2
      suggests stimulation of Ca(2+)-dependent apoptosis. Moreover, activation of the
      mitochondrial apoptotic pathway results from a time-dependent multi-factorial
      impairment as inferred from the stepwise characterization of constitutive pro-
      and anti-apoptotic factors. Activation of serine-threonine protein phosphatase 2A
      (PP2A) was also found in Huh7 cells upon HSV-1 Cgal(+) infection. In addition,
      PP2A activation paralleled dephosphorylation and inactivation of downstream
      mitogen-activated protein (MAP) kinase pathway (MEK(1/2), ERK(1/2)) critical to
      cell survival and activation of proapoptotic Bad by dephosphorylation of Ser-112.
      Taken together, our results provide novel molecular information that contributes
      to define in detail the apoptotic mechanisms triggered by HSV-1 Cgal(+) in the
      host cell and lead to the implication of PP2A in the transduction of cell death
      signals and cell survival pathway arrest.

PMID- 19098280
TI  - Are the original and second edition of the California Verbal Learning Test
      equally accurate in detecting malingering?
AB  - This two-part study sought to determine the equivalence of the California Verbal
      Learning Tests (CVLT-1 and CVLT-2) in the detection of malingering in traumatic
      brain injury (TBI) and chronic pain. Part 1 compared a variety of scores from the
      two versions in carefully matched patient groups. Part 2 used criterion groups
      (known-groups) methodology to examine the relative rates of false positive (FP)
      errors across the two versions. Participants were 442 TBI (CVLT-1 = 310; CVLT-2 =
      132) and 378 chronic pain patients (CVLT-1 = 250; CVLT-2 = 128). Overall, the
      CVLT-2 was more difficult than the CVLT-1, with the chronic pain patients showing
      larger version effects than the TBI patients. The two versions of the CVLT were
      equally accurate in detecting malingering in TBI and chronic pain. However, they
      were not interchangeable. The use of CVLT-1 cutoffs with the CVLT-2 may result in
      an increased risk of FP error. Appropriate cutoff adjustment in clinical practice
      is recommended.

PMID- 19098281
TI  - Update of the LIPID MAPS comprehensive classification system for lipids.
AB  - In 2005, the International Lipid Classification and Nomenclature Committee under
      the sponsorship of the LIPID MAPS Consortium developed and established a
      "Comprehensive Classification System for Lipids" based on well-defined chemical
      and biochemical principles and using an ontology that is extensible, flexible,
      and scalable. This classification system, which is compatible with contemporary
      databasing and informatics needs, has now been accepted internationally and
      widely adopted. In response to considerable attention and requests from lipid
      researchers from around the globe and in a variety of fields, the comprehensive
      classification system has undergone significant revisions over the last few years
      to more fully represent lipid structures from a wider variety of sources and to
      provide additional levels of detail as necessary. The details of this
      classification system are reviewed and updated and are presented here, along with
      revisions to its suggested nomenclature and structure-drawing recommendations for
      lipids.

PMID- 19098282
TI  - Semisynthesis and segmental isotope labeling of the apoE3 N-terminal domain using
      expressed protein ligation.
AB  - Apolipoprotein E (apoE) is an exchangeable apolipoprotein that functions as a
      ligand for members of the LDL receptor family, promoting lipoprotein clearance
      from the circulation. Productive receptor binding requires that apoE adopt an LDL
      receptor-active conformation through lipid association, and studies have shown
      that the 22 kDa N-terminal (NT) domain (residues 1-183) of apoE is both necessary
      and sufficient for receptor interaction. Using intein-mediated expressed protein
      ligation (EPL), a semisynthetic apoE3 NT has been generated for use in structure
      function studies designed to probe the nature of the lipid-associated
      conformation of the protein. Circular dichroism spectroscopy of EPL-generated
      apoE3 NT revealed a secondary structure content similar to wild-type apoE3 NT.
      Likewise, lipid and LDL receptor binding studies revealed that EPL-generated
      apoE3 NT is functional. Subsequently, EPL was used to construct an apoE3 NT
      enriched with 15N solely and specifically in residues 112-183. 1H-15N
      heteronuclear single quantum correlation spectroscopy experiments revealed that
      the ligation product is correctly folded in solution, adopting a conformation
      similar to wild-type apoE3-NT. The results indicate that segmental isotope
      labeling can be used to define the lipid bound conformation of the receptor
      binding element of apoE as well as molecular details of its interaction with the
      LDL receptor.

PMID- 19098283
TI  - Dimyristoylphosphotidylcholine induces conformational changes in apoB that lowers
      lipoprotein(a).
AB  - Lipoprotein(a) [Lp(a)] is assembled by the binding of apolipoprotein B (apoB)
      lysine residues on LDL to lysine binding sites in apolipoprotein(a) [apo(a)] and
      the subsequent formation of a disulphide bond between apoB and apo(a). In this
      study, we induced changes in apoB conformation by adding phospholipids to LDL and
      tested the effect of the altered apoB conformation on Lp(a) assembly. The
      addition of dimyristoylphosphatidylcholine (DMPC) to isolated LDL induced a
      decrease in the alpha-helical content of apoB and increased the immunoreactivity
      of the apoB C terminus toward monoclonal antibodies in the region. These
      conformational changes were associated with a reduction in the ability of the
      DMPC-modified LDL to form Lp(a) in in vitro assays. Furthermore, administration
      of DMPC to Lp(a) transgenic mice lead to a significant but transient decrease in
      Lp(a) levels (18.6% decrease at 2 h, P < 0.001) which coincided with the
      association of DMPC with LDL in plasma. Our study shows that changes in apoB
      conformation in the C-terminal region alter the exposure of sequences required
      for Lp(a) assembly and reduce the formation of Lp(a) both in vitro and in vivo.
      We conclude that manipulation of LDL surface phospholipids alters Lp(a) levels.

PMID- 19098284
TI  - What is the relevance of lung epithelial cells during the dissemination of spores
      in inhalational anthrax?

PMID- 19098285
TI  - Discovery and scoring of protein interaction subnetworks discriminative of late
      stage human colon cancer.
AB  - We used a systems biology approach to identify and score protein interaction
      subnetworks whose activity patterns are discriminative of late stage human
      colorectal cancer (CRC) versus control in colonic tissue. We conducted two gel
      based proteomics experiments to identify significantly changing proteins between
      normal and late stage tumor tissues obtained from an adequately sized cohort of
      human patients. A total of 67 proteins identified by these experiments was used
      to seed a search for protein-protein interaction subnetworks. A scoring scheme
      based on mutual information, calculated using gene expression data as a proxy for
      subnetwork activity, was developed to score the targets in the subnetworks. Based
      on this scoring, the subnetwork was pruned to identify the specific protein
      combinations that were significantly discriminative of late stage cancer versus
      control. These combinations could not be discovered using only proteomics data or
      by merely clustering the gene expression data. We then analyzed the resultant
      pruned subnetwork for biological relevance to human CRC. A number of the proteins
      in these smaller subnetworks have been associated with the progression (CSNK2A2,
      PLK1, and IGFBP3) or metastatic potential (PDGFRB) of CRC. Others have been
      recently identified as potential markers of CRC (IFITM1), and the role of others
      is largely unknown in this disease (CCT3, CCT5, CCT7, and GNA12). The functional
      interactions represented by these signatures provide new experimental hypotheses
      that merit follow-on validation for biological significance in this disease.
      Overall the method outlines a quantitative approach for integrating proteomics
      data, gene expression data, and the wealth of accumulated legacy experimental
      data to discover significant protein subnetworks specific to disease.

PMID- 19098286
TI  - Isolation and functional characterization of CYP71AJ4 encoding for the first P450
      monooxygenase of angular furanocoumarin biosynthesis.
AB  - The biosynthesis of linear and angular furanocoumarins is still poorly understood
      at the molecular level, with only psoralen synthase (CYP71AJ1) identified from
      Ammi majus. Using cDNA probes inferred from CYP71AJ1, three orthologs were
      isolated from Apium graveolens (CYP71AJ2) and Pastinaca sativa (CYP71AJ3 and -4)
      and functionally expressed in yeast cells. CYP71AJ2 and CYP71AJ3 displayed
      psoralen synthase activity, whereas CYP71AJ4 only catalyzed the conversion of (+)
      columbianetin to angelicin and negligible amounts of a hydroxylated columbianetin
      by-product. CYP71AJ4 thus constitutes the first fully characterized P450
      monooxygenase specific for the angular furanocoumarin pathway. The angelicin
      synthase exhibited an apparent K(m) of 2.1 +/- 0.4 microm for (+)-columbianetin
      and a k(cat) of 112 +/- 14 min(-1). Moreover, the use of 3'-deuterated (+)
      columbianetin as substrate led to an almost complete "metabolic switch,"
      resulting in the synthesis of anti-3'-hydroxy-3'-deuterated(+)-columbianetin.
      This confirms that angelicin synthase attacks columbianetin by syn-elimination of
      hydrogen from C-3'. Sequence comparison between psoralen synthase (CYP71AJ3) and
      angelicin synthase (CYP71AJ4) showed 70% identity, whereas the identity dropped
      to 40% in those regions thought to provide the substrate recognition sites.
      Accordingly, CYP71AJ3 and CYP71AJ4 might be derived from a common ancestor of
      unknown functionality by gene duplication and subsequent molecular evolution.

PMID- 19098287
TI  - RIAM activates integrins by linking talin to ras GTPase membrane-targeting
      sequences.
AB  - Rap1 small GTPases interact with Rap1-GTP-interacting adaptor molecule (RIAM), a
      member of the MRL (Mig-10/RIAM/Lamellipodin) protein family, to promote talin
      dependent integrin activation. Here, we show that MRL proteins function as
      scaffolds that connect the membrane targeting sequences in Ras GTPases to talin,
      thereby recruiting talin to the plasma membrane and activating integrins. The MRL
      proteins bound directly to talin via short, N-terminal sequences predicted to
      form amphipathic helices. RIAM-induced integrin activation required both its
      capacity to bind to Rap1 and to talin. Moreover, we constructed a minimized 50
      residue Rap-RIAM module containing the talin binding site of RIAM joined to the
      membrane-targeting sequence of Rap1A. This minimized Rap-RIAM module was
      sufficient to target talin to the plasma membrane and to mediate integrin
      activation, even in the absence of Rap1 activity. We identified a short talin
      binding sequence in Lamellipodin (Lpd), another MRL protein; talin binding Lpd
      sequence joined to a Rap1 membrane-targeting sequence is sufficient to recruit
      talin and activate integrins. These data establish the mechanism whereby MRL
      proteins interact with both talin and Ras GTPases to activate integrins.

PMID- 19098289
TI  - Tissue-nonspecific alkaline phosphatase is required for the calcification of
      collagen in serum: a possible mechanism for biomineralization.
AB  - Previous studies have shown that the type I collagen of tendon and demineralized
      bone both calcify rapidly in serum. The speed, collagen matrix-type specificity,
      and extent of the re-calcification of demineralized bone in serum suggest that
      the serum calcification activity identified in these studies may participate in
      normal biomineralization. Because of its presence in serum and its long history
      of association with the normal mineralization of the collagen matrix of bone,
      tissue-nonspecific alkaline phosphatase (TNAP) is an obvious candidate for a
      protein that could be a component of serum calcification activity, and
      experiments were therefore carried out to test this possibility. These
      experiments show that the inactivation of TNAP in serum prevents collagen
      calcification, and that the addition of physiological levels of purified TNAP
      restores the ability of TNAP-deficient serum to calcify collagen. Additional
      experiments show that the role of TNAP in collagen calcification is to activate a
      serum nucleator of apatite crystal formation. Based on these and earlier studies,
      the mechanism of collagen calcification in serum requires at least four elements
      as follows. 1) A matrix (collagen fibrils) that is accessible to small apatite
      crystals but not large molecules ( Toroian, D., Lim, J. E., and Price, P. A.
      (2007) J. Biol. Chem. 282, 22437-22447 ). 2) A large serum nucleator that
      generates small crystals, some of which diffuse into the fibrils. 3) A source of
      TNAP to activate the serum nucleator. 4) A large protein (fetuin) that
      selectively inhibits growth of crystals remaining in solution, thereby ensuring
      that only crystals within fibrils grow ( Toroian, D. T., and Price, P. A. (2008)
      Calcif. Tissue Int. 82, 116-126 ).

PMID- 19098290
TI  - Cost-effectiveness of atrial fibrillation catheter ablation.
AB  - Radiofrequency catheter ablation has become an established treatment option for
      the management of patients with atrial fibrillation (AF). Although the concept of
      a rhythm control strategy devoid of the adverse events related to antiarrhythmic
      treatment seems highly attractive, further steps are needed in order to improve
      our understanding of the underlying pathophysiology, refine our ablative
      techniques, and increase our therapeutic efficacy. Furthermore, the increased
      cost of AF catheter ablation combined with the substantial number of potential
      candidates also mandates the evaluation of this invasive treatment through a cost
      effectiveness prism. In the present review, we recapitulate the existing evidence
      pertaining to cost-effectiveness of AF catheter ablation as well as the
      shortcomings, peculiarities, and distinctive aspects of such a cost-to-benefit
      analysis.

PMID- 19098288
TI  - Suppression of the deubiquitinating enzyme USP5 causes the accumulation of
      unanchored polyubiquitin and the activation of p53.
AB  - Both p53 and its repressor Mdm2 are subject to ubiquitination and proteasomal
      degradation. We show that knockdown of the deubiquitinating enzyme USP5
      (isopeptidase T) results in an increase in the level and transcriptional activity
      of p53. Suppression of USP5 stabilizes p53, whereas it has little or no effect on
      the stability of Mdm2. This provides a mechanism for transcriptional activation
      of p53. USP5 knockdown interferes with the degradation of ubiquitinated p53
      rather than attenuating p53 ubiquitination. In vitro studies have shown that a
      preferred substrate for USP5 is unanchored polyubiquitin. Consistent with this,
      we observed for the first time in a mammalian system that USP5 makes a major
      contribution to Lys-48-linked polyubiquitin disassembly and that suppression of
      USP5 results in the accumulation of unanchored polyubiquitin chains. Ectopic
      expression of a C-terminal mutant of ubiquitin (G75A/G76A), which also causes the
      accumulation of free polyubiquitin, recapitulates the effects of USP5 knockdown
      on the p53 pathway. We propose a model in which p53 is selectively stabilized
      because the unanchored polyubiquitin that accumulates after USP5 knockdown is
      able to compete with ubiquitinated p53 but not with Mdm2 for proteasomal
      recognition. This raises the possibility that there are significant differences
      in proteasomal recognition of p53 and Mdm2. These differences could be exploited
      therapeutically. Our study reveals a novel mechanism for regulation of p53 and
      identifies USP5 as a potential target for p53 activating therapeutic agents for
      the treatment of cancer.

PMID- 19098291
TI  - Stress affects uterine receptivity through an ovarian-independent pathway.
AB  - BACKGROUND: Although stress is known to disturb natural fertility through the
      inhibition of the hypothalamic-pituitary-gonadal (HPG) axis, the impact of stress
      on infertile women who receive exogenous gonadal hormones is not well defined.
      This is probably due to lack of experimental models for evaluating the impacts of
      stress through an ovarian-independent pathway. The objective of this study was to
      investigate the possible impact of stress on uterine receptivity, independent of
      HPG axis dysfunction, using a mouse implantation model maintained with hormone
      supplementation. METHODS: Blastocysts from donor mice were transferred into the
      uterine lumen of ovariectomized (OVX) Balb/c female recipient mice following
      supplementation with estradiol and progesterone. The recipients were divided into
      two groups: those exposed (stress group) or not exposed (control group) to
      intermittent sonic exposure prior to embryo transfer (ET). The number of
      implantation sites (IS) was compared between these groups. Microarray analysis
      was performed to elucidate stress-induced molecular alterations in uteri during
      the implantation period. Sequential gene expression of leukemia inhibitory factor
      (Lif), an estradiol-inducible gene, was also analyzed using real-time PCR.
      RESULTS: A non-mating OVX model with satisfactory implantation rates was
      established. The number of IS in the stress group (n = 20) was significantly less
      than that in the control group (n = 18) (Mann-Whitney test, P = 0.0375).
      Implantation-related genes and ovarian-hormone-responsive genes were repressed in
      the stress group despite ovarian hormone supplementation. The expression of Lif
      was suppressed in the stress group. CONCLUSIONS: Stress can cause decreased
      uterine receptivity through an ovarian-independent pathway.

PMID- 19098292
TI  - Age- and substrain-dependent sperm abnormalities in BALB/c mice and functional
      assessment of abnormal sperm by ICSI.
AB  - BACKGROUND: Male BALB/c mice produce a high proportion of morphologically
      abnormal sperm. Although the BALB/c male may be a useful model of human male
      infertility, it remains unclear whether the sperm abnormality rate (SAR) is
      affected by age or the BALB/c substrain. METHODS: SARs (head shape) were assessed
      in three BALB/c substrains (A, AnN, ByJ) at 7 and 9 weeks and 6-10 months of age
      (c.100 sperm/male). The functional ability of abnormal sperm produced from 7-week
      old and 6-10-month-old males was determined in BALB/c AnN mice by ICSI. RESULTS:
      The SAR (quasi-normal plus abnormal sperm) was lower in BALB/c A than in the
      other two strains (P < 0.05). Further, the SARs of BALB/c AnN and ByJ strains at
      7 weeks old were high and decreased rapidly by 9 weeks, suggesting that early
      spermatogenesis (i.e. the first wave of spermatogenesis) produced low-quality
      sperm. ICSI experiments indicated that 2-cell stage embryos which developed from
      morphologically abnormal sperm from both the first wave of spermatogenesis and
      the older mice (6-10 months) were similar to those from morphologically normal
      sperm in terms of producing progeny, although the number of 2-cell embryos was
      slightly lower (P < 0.05, chi(2) test) than with normal sperm. CONCLUSIONS:
      Although the SARs of BALB/c mice are affected by both age and substrain, the
      embryos that developed from morphologically abnormal sperm have normal genetic
      potential in terms of production of progeny.

PMID- 19098293
TI  - Staying connected: neighbourhood correlates of social participation among older
      adults living in an urban environment in Montreal, Quebec.
AB  - Alongside community involvement, promoting social participation has been
      identified as a key strategy of fostering empowerment, one of the central tenets
      of the health promotion movement. Engagement in social and productive activities
      appears to be particularly beneficial to older adults, as it has been found to be
      associated with positive outcomes on a variety of health indicators. It is
      therefore critical to identify factors that might lead to greater social
      participation within these age groups. The objective of this study was to
      investigate the relationship between perceptions of neighbourhood user
      friendliness and social participation while controlling for personal
      characteristics in a sample of seniors living in an urban environment. A
      convenience sample of older adults (n = 282) was recruited through community
      organizations located in high- average- and low-income Montreal neighbourhoods.
      Data were collected via an interviewer-administered questionnaire assessing
      social participation and various variables at the neighbourhood level (e.g.
      housing and social environment, walking environment and transportation, and
      services and amenities) and at the individual-level (e.g. health status and socio
      demographic characteristics). Five variables emerged as independent predictors of
      social participation. Positive predictors retained in the final regression model
      included frequent walking episodes (almost every day), higher Vitality and
      General Health SF-12v2 scores, and perceived accessibility to key resources for
      older adults. Also included was a negative predictor: age (R2 of the final model
      = 0.28). Implications of the findings for research and action pertaining to
      ecological, health promotion interventions for older adults are identified.

PMID- 19098294
TI  - Effect of tunicamycin on Candida albicans biofilm formation and maintenance.
AB  - BACKGROUND: Candida albicans is a common opportunistic pathogen of the human body
      and is the frequent causative agent of candidiasis. Typically, these infections
      are associated with the formation of biofilms on both host tissues and implanted
      biomaterials. As a result of the intrinsic resistance of C. albicans biofilms to
      most antifungal agents, new strategies are needed to combat these infections.
      METHODS: Here we have used a 96-well microtitre plate model of C. albicans
      biofilm formation to study the inhibitory effect of tunicamycin, a nucleoside
      antibiotic that inhibits N-linked glycosylation affecting cell wall and secreted
      proteins, on C. albicans biofilm formation. A proteomic approach was used to
      study the effect of tunicamycin on levels of glycosylation of key secreted
      mannoproteins in the biofilm matrix. RESULTS: Our results revealed that
      physiological concentrations of tunicamycin displayed significant inhibitory
      effects on biofilm development and maintenance, while not affecting overall cell
      growth or morphology. However, tunicamycin exerted a minimal effect on fully
      mature, pre-formed C. albicans biofilms. CONCLUSIONS: The effect of tunicamycin
      on the C. albicans biofilm mode of growth demonstrates the importance of N-linked
      glycosylation in the developmental stages of biofilm formation. In addition, our
      results indicate that N-linked glycosylation represents an attractive target for
      the development of alternative strategies for the prevention of biofilm formation
      by this important pathogenic fungus.

PMID- 19098295
TI  - Furanones, potential agents for preventing Staphylococcus epidermidis biofilm
      infections?
AB  - OBJECTIVES: Staphylococcus epidermidis is often associated with biofilm
      infections related to medical implants. The aim of the present study was to find
      furanones that decrease biofilm formation without irritative or genotoxic
      effects, or effects on S. epidermidis growth. METHODS: After screening including
      bioluminescence and biofilm assays, 2 furanones out of 11 were chosen for further
      studies. MIC values of the two furanones were established to determine whether
      biofilm inhibition effects were ascribed to inhibition of bacterial growth. To
      further investigate interference with communication, the effect of the furanones
      was tested in the presence of the autoinducer-2 precursor (S)-4,5-dihydroxy-2,3
      pentanedione. The furanones were tested for possible irritative effects by the
      Hen's egg test chorioallantoic membrane procedure. Finally, potential genotoxic
      effects in mice were assessed by a membrane array, and effects on global gene
      expression were investigated by using a microarray representing 30,000 genes of
      the mouse genome. RESULTS: From the bioluminescence assay, 4 furanones out of 11
      were chosen for further biofilm analyses. Biofilm formation by S. epidermidis was
      significantly decreased by the four furanones tested at concentrations not
      affecting microbial growth. Two furanones were chosen for further studies: one
      that decreased biofilm statistically more than the others and one containing two
      bromo substituents. The two furanones were found to be non-irritative and non
      genotoxic at the concentrations used. CONCLUSIONS: Furanones may inhibit biofilm
      formation through interference with quorum sensing and thus represent promising
      agents for protecting surfaces from being colonized by S. epidermidis.

PMID- 19098297
TI  - The Biological Safety of Stainless Steel Needles Used in Warm-needling.
AB  - Warm-needling (also called thermo-acupuncture) is a combination of acupuncture
      and moxibustion. Due to the intense heat involved, there have been concerns over
      the biological safety of the acuneedles used in the treatment. This paper reports
      two phases of a safety test. For a preliminary test, we compared the temperature
      change patterns of stainless steel (SS304) needles and traditional gold alloy
      needles, which have been increasingly replaced by the former. To verify the
      effects of the presence of coating materials, the main test involved three
      different kinds of SS304: silicone-coated, salicylic acid-coated and non-coated
      needles. Each group of needles was tested for pH level, heavy metals and UV
      absorbance spectrum along with biological tests on the cytotoxicity and hemolysis
      of the needle. All the tests on the extractants from the needles were negative.
      In the biological tests, each test result showed a significant difference from
      the positive control samples, while no significant difference was observed
      compared with the negative control samples. In the hemolysis tests, all samples
      satisfied the Korean Government Standards. All the results suggest that SS304
      needles are biologically safe to be used in warm-needling, though they can be
      improved to perform as well as the gold alloy needles in terms of temperature
      fluctuations.

PMID- 19098296
TI  - Complementary and Alternative Medicine: Comparison of Current Knowledge,
      Attitudes and Interest among German Medical Students and Doctors.
AB  - Although it has been agreed that complementary and alternative medicine (CAM)
      should be included in the German medical curriculum, there is no consensus on
      which methods and how it should be taught. This study aimed to assess needs for
      CAM education by evaluating current knowledge, attitudes and interests of medical
      students, general physicians and gynecologists. Two instruments based on
      established and validated questionnaires were developed. One was given to seventh
      semester medical students and the other to office-based doctors. Data were
      analyzed by bivariate correlation and cross-tabulation. Altogether 550
      questionnaires were distributed-280 to doctors and 270 to medical students.
      Completed questionnaires were returned by 80.4% of students and 78.2% of doctors.
      Although 73.8% (160/219) of doctors and 40% (87/217) of students had already
      informed themselves about CAM, neither group felt that they knew much about CAM.
      Doctors believed that CAM was most useful in general medicine, supportive
      oncology, pediatrics, dermatology and gynecology, while students believed that
      dermatology, general medicine, psychiatry and rheumatology offered opportunities;
      both recommended that CAM should be taught in these areas. Both groups believed
      that CAM should be included in medical education; however, they believed that CAM
      needed more investigation and should be taught "critically". German doctors and
      students would like to be better informed about CAM. An approach which teaches
      fundamental competences to students, chooses specific content based on evidence,
      demographics and medical conditions and provides students with the skills they
      need for future learning should be adopted.

PMID- 19098298
TI  - Does reversal of oxidative stress and inflammation provide vascular protection?
AB  - Chronic inflammation is a pathogenic feature of atherosclerosis and
      cardiovascular disease mediated by substances including angiotensin II,
      proinflammatory cytokines, and free fatty acids. This promotes generation of
      reactive oxygen species in vascular endothelial cells and smooth muscle cells,
      which mediate injury through several mechanisms. Reciprocal relationships between
      endothelial dysfunction and insulin resistance as well as cross-talk between
      hyperlipidaemia and the renin-angiotensin-aldosterone system (RAAS) at multiple
      levels contribute importantly to a variety of risk factors. Therefore,
      combination therapy that simultaneously addresses multiple mechanisms for the
      pathogenesis of atherosclerosis is an attractive emerging concept for slowing
      progression of atherosclerosis. Combined therapy with statins, peroxisome
      proliferator-activated receptors, and RAAS blockade demonstrates additive
      beneficial effects on endothelial dysfunction and insulin resistance when
      compared with monotherapies in patients with cardiovascular risk factors due to
      both distinct and interrelated mechanisms. These additive beneficial effects of
      combined therapies are consistent with laboratory and recent clinical studies.
      Thus, combination therapy may be an important paradigm for treating and slowing
      progression of atherosclerosis, coronary heart disease, and co-morbid metabolic
      disorders characterized by endothelial dysfunction and insulin resistance.

PMID- 19098299
TI  - Genetics and pathophysiology of arterial stiffness.
AB  - Arterial stiffness is a cardiovascular risk factor that is independent of
      arterial pressure. Clinically, carotid-femoral pulse wave velocity (PWV) is the
      gold-standard parameter of arterial stiffness. Recent genetic studies have
      revealed specific genes that contribute to arterial stiffening. Here we review
      the recent findings on genome-wide linkage analyses and candidate gene
      polymorphism association studies. We also focus on the latest advances in the
      identification of gene variants affecting PWV using high density array single
      nucleotide polymorphism technology in a recent genome-wide association (GWA)
      study. Linkage and polymorphism studies revealed a first group of genes affecting
      the renin-angiotensin-aldosterone system, elastic fibre structural components,
      metalloproteinases, and the NO pathway. A second group of genes, identified by
      polymorphism association studies and possibly involved in the pathophysiology of
      arterial stiffness, includes beta-adrenergic receptors, endothelin receptors, and
      inflammatory molecules. The last group of genes, identified by GWA studies and
      unrelated to currently suspected mechanisms of arterial stiffness, may target
      transcriptional pathways controlling gene expression, differentiation of vascular
      smooth muscle cells, apoptosis of endothelial cells, or the immune response
      within the vascular wall.

PMID- 19098300
TI  - A pyrrole-imidazole polyamide targeting transforming growth factor-beta1 inhibits
      restenosis and preserves endothelialization in the injured artery.
AB  - AIMS: Although the use of drug-eluting stents (DESs) has been shown to limit
      neointima hyperplasia, currently available DESs may adversely affect re
      endothelialization. To evaluate whether a novel gene silencer pyrrole-imidazole
      (PI) polyamide targeting transforming growth factor (TGF)-beta1 is a candidate
      agent for the DESs, we examined the effects of PI polyamide targeting the TGF
      beta1 promoter on neointimal formation in rat carotid artery after balloon
      injury. METHODS AND RESULTS: PI polyamide was designed to span the boundary of
      the AP-1 binding site of the TGF-beta1 promoter. After inducing balloon injury to
      arteries, incubation with PI polyamide was carried out for 10 min. Neointimal
      thickening and re-endothelialization were evaluated at 21 days after injury.
      Fluoresceinisothiocyanate-labelled PI polyamide was distributed into most of the
      nuclei in the injured artery without any delivery reagents. PI polyamide (100
      microg) significantly inhibited neointimal thickening at 21 days after injury by
      57%. PI polyamide targeting TGF-beta1 significantly decreased the expression of
      TGF-beta1 mRNA and protein in the artery at 3 days after injury and also
      suppressed the expression of connective tissue growth factor (CTGF), fibronectin,
      collagen type 1, and lectin-like ox-LDL receptor-1 mRNAs. A morphometric analysis
      showed that PI polyamide targeting TGF-beta1 accelerated re-endothelialization in
      the injured artery. CONCLUSION: These findings suggest that the synthetic PI
      polyamide targeting the TGF-beta1 promoter may have the potential to suppress
      neointimal hyperplasia after arterial injury by the down-regulation of TGF-beta1
      and CTGF and the reduction of the extracellular matrix. As a result, PI polyamide
      targeting TGF-beta1 may therefore be a potentially effective agent for the
      treatment of in-stent restenosis, as a candidate agent for the next-generation
      DES.

PMID- 19098301
TI  - The analysis of inconsistencies between cytogenetic annotations and sequence
      mapping by defining the imprecision zones of cytogenetic banding.
AB  - MOTIVATION: In current databases, there are many genes with inconsistent mapping
      positions between their cytogenetic annotations and sequence map positions.
      However, not all inconsistencies are the same. Some of them may be problematic
      which should be corrected in the future; while others may result from the
      imprecise nature of chromosomal banding which may be tolerable. It is important
      to stratify the cytogenetic position information into different confidence groups
      with the recognition of the impreciseness of cytogenetic banding. RESULTS: When
      plotting their cytogenetic annotations against sequence map positions on a 2D
      plane, the consistent genes tend to have a compact linear distribution; while
      genes with inconsistent positions are more scattered. The overlapping areas
      between these two groups are defined as the tolerable imprecision zones by linear
      regression and distance analysis. The system was implemented using sequence
      information from NCBI Map Viewer Build 36.3 and cytogenetic annotations from NCBI
      Entrez Gene. The genes' position information is classified into five confidence
      groups: inconsistent-intolerable, inconsistent-tolerable, consistent-imprecise,
      consistent-precise and consistent-rough. Using information from NCBI Map Viewer
      Build 36.3 and NCBI Entrez Gene, the percentages of these confidence groups are
      1.4%, 7.0%, 54.0%, 35.4% and 2.2%, respectively. Using information from NCBI Map
      Viewer Build 36.3 and NCBI online Mendelian inheritance in man (OMIM), the
      percentages are 3.7%, 16.9%, 49.0%, 19.0% and 11.4%, respectively. Combining
      these two results, a confidence table of genes' position information was
      constructed. AVAILABILITY: The detailed results are accessible over the Internet
      at http://centrallab.hosp.ncku.edu.tw/imz.

PMID- 19098302
TI  - Procalcitonin at the onset of giant cell arteritis and polymyalgia rheumatica:
      the GRACG prospective study.
AB  - OBJECTIVES: An epidemic pattern has been reported for GCA and PMR. Immunological
      studies have shown that an unknown antigen activates the dendritic cells of the
      adventitia and the type 4 toll-like receptors. Procalcitonin (PCT) is an early
      marker of bacterial infection. The goal of the study was to assess the level of
      PCT in GCA and PMR at the onset of the disease. METHODS: Patients diagnosed
      during the 2002-06 period were randomly selected. All the 46 patients fulfilled
      the ACR or the Hunder criteria, and all blood samples were taken before steroid
      therapy. RESULTS: PCT was normal in all patients. PCT was slightly increased in
      men (0.087 +/- 0.023 microg/l) compared with women (0.066 +/- 0.027 microg/l) (P
      = 0.009), and in PMR (0.092 +/- 0.027 microg/l) compared with GCA (0.068 +/-
      0.026 microg/l) (P = 0.018). There was no significant correlation with
      inflammation markers. CONCLUSIONS: These results are not in favour of a bacterial
      trigger for GCA or PMR. Increased PCT levels in patients with inflammatory
      syndrome, GCA-PMR symptoms and negative temporal artery biopsy may rule out the
      diagnosis of GCA and PMR.

PMID- 19098303
TI  - Velocity and deformation imaging for the assessment of myocardial dysfunction.
AB  - Recent developments in echocardiographic imaging technology and processing
      enabled the quantification of myocardial motion and deformation in a clinical
      setting. Echocardiographic strain (-rate) imaging provides a relatively easy way
      to study myocardial deformation. However, although (local) deformation is clearly
      linked to cardiac (dys-) function, it is important to understand how this
      information can be used in clinical practice and how specific deformation
      patterns should be interpreted. This review paper first discusses which issues
      are important to address when assessing cardiac function and how (regional)
      deformation and myocardial contractility are related. The use and interpretation
      of deformation profiles is further illustrated for some typical cardiac
      pathologies. The observed deformation patterns are discussed in light of the
      changes in regional contractility (ischemia), timing of contractile force
      development (LBBB and heart failure), pressure/volume overload, and assessing
      diastolic function.

PMID- 19098304
TI  - Misrepresentation of the outside world or self may follow damage to the nervous
      system.

PMID- 19098306
TI  - Nuclear export of the rate-limiting enzyme in phosphatidylcholine synthesis is
      mediated by its membrane binding domain.
AB  - CTP:phosphocholine cytidylyltransferase alpha (CCTalpha), the rate-limiting
      enzyme in the CDP-choline pathway for phosphatidylcholine (PtdCho) synthesis, is
      activated by translocation to nuclear membranes. However, CCTalpha is cytoplasmic
      in cells with increased capacity for PtdCho synthesis and following acute
      activation, suggesting that nuclear export is linked to activation. The objective
      of this study was to identify which CCTalpha domains were involved in nuclear
      export in response to the lipid activators farnesol (FOH) and oleate. Imaging of
      CCT-green fluorescent protein (GFP) mutants expressed in CCTalpha-deficient CHO58
      cells showed that FOH-mediated translocation to nuclear membranes and export to
      the cytoplasm required the membrane binding amphipathic helix (domain M). Nuclear
      export was reduced by a mutation that mimics constitutive phosphorylation of the
      CCT phosphorylation (P) domain. However, domain M alone was sufficient to promote
      translocation to the nuclear envelope and export of a nuclear-localized GFP
      construct in FOH- or oleate-treated CHO58 cells. In the context of acute
      activation with lipid mediators, nuclear export of CCT-GFP mutants correlated
      with in vitro activity but not PtdCho synthesis. This study describes a nuclear
      export pathway that is dependent on membrane interaction of an amphipathic helix,
      thus linking lipid-dependent activation to the nuclear/cytoplasmic distribution
      of CCTalpha.

PMID- 19098305
TI  - Plant phospholipid signaling: "in a nutshell".
AB  - Since the discovery of the phosphoinositide/phospholipase C (PI/PLC) system in
      animal systems, we know that phospholipids are much more then just structural
      components of biological membranes. In the beginning, this idea was fairly
      straightforward. Receptor stimulation activates PLC, which hydrolyses
      phosphatidylinositol4,5-bisphosphate [PtdIns(4,5)P2] into two second messengers:
      inositol 1,4,5-trisphosphate (InsP3) and diacylglycerol (DG). While InsP3 difuses
      into the cytosol and triggers the release of calcium from an internal store via
      ligand-gated calcium channels, DG remains in the membrane where it recruits and
      activates members of the PKC family. The increase in calcium, together with the
      change in phosphorylation status, (in)activates a variety of protein targets,
      leading to a massive reprogramming, allowing the cell to appropriately respond to
      the extracellular stimulus. Later, it became obvious that not just PLC, but a
      variety of other phospholipid-metabolizing enzymes were activated, including
      phospholipase A, phospholipase D, and PI 3-kinase. More recently, it has become
      apparent that PtdIns4P and PtdIns(4,5)P2 are not just signal precursors but can
      also function as signaling molecules themselves. While plants contain most of the
      components described above, and evidence for their role in cell signaling is
      progressively increasing, major differences between plants and the mammalian
      paradigms exist. Below, these are described "in a nutshell."

PMID- 19098307
TI  - Localization and structure of the ankyrin-binding site on beta2-spectrin.
AB  - Spectrins are tetrameric actin-cross-linking proteins that form an elastic
      network, termed the membrane skeleton, on the cytoplasmic surface of cellular
      membranes. At the plasma membrane, the membrane skeleton provides essential
      support, preventing loss of membrane material to environmental shear stresses.
      The skeleton also controls the location, abundance, and activity of membrane
      proteins that are critical to cell and tissue function. The ability of the
      skeleton to modulate membrane stability and function requires adaptor proteins
      that bind the skeleton to membranes. The principal adaptors are the ankyrin
      proteins, which bind to the beta-subunit of spectrin and to the cytoplasmic
      domains of numerous integral membrane proteins. Here, we present the crystal
      structure of the ankyrin-binding domain of human beta2-spectrin at 1.95 A
      resolution together with mutagenesis data identifying the binding surface for
      ankyrins on beta2-spectrin.

PMID- 19098308
TI  - Thermodynamic analysis reveals a temperature-dependent change in the catalytic
      mechanism of bacillus stearothermophilus tyrosyl-tRNA synthetase.
AB  - Catalysis of tRNA(Tyr) aminoacylation by tyrosyl-tRNA synthetase can be divided
      into two steps. In the first step, tyrosine is activated by ATP to form the
      tyrosyl-adenylate intermediate. In the second step, the tyrosyl moiety is
      transferred to the 3' end of tRNA. To investigate the roles that enthalpic and
      entropic contributions play in catalysis by Bacillus stearothermophilus tyrosyl
      tRNA synthetase (TyrRS), the temperature dependence for the activation of
      tyrosine and subsequent transfer to tRNA(Tyr) has been determined using single
      turnover kinetic methods. A van't Hoff plot for binding of ATP to the TyrRS.Tyr
      complex reveals three distinct regions. Particularly striking is the change
      occurring at 25 degrees C, where the values of DeltaH(0) and DeltaS(0) go from 
      144 kJ/mol and -438 J/mol K below 25 degrees C to +137.9 kJ/mol and +507 J/mol K
      above 25 degrees C. Nonlinear Eyring and van't Hoff plots are also observed for
      formation of the TyrRS.[Tyr-ATP](double dagger) and TyrRS.Tyr-AMP complexes.
      Comparing the van't Hoff plots for the binding of ATP to tyrosyl-tRNA synthetase
      in the absence and presence of saturating tyrosine concentrations indicates that
      the temperature-dependent changes in DeltaH(0) and DeltaS(0) for the binding of
      ATP only occur when tyrosine is bound to the enzyme. Previous investigations
      revealed a similar synergistic interaction between the tyrosine and ATP
      substrates when the "KMSKS" signature sequence is deleted or replaced by a
      nonfunctional sequence. We propose that the temperature-dependent changes in
      DeltaH(0) and DeltaS(0) are because of the KMSKS signature sequence being
      conformationally constrained and unable to disrupt this synergistic interaction
      below 25 degrees C.

PMID- 19098309
TI  - Cysteine string protein promotes proteasomal degradation of the cystic fibrosis
      transmembrane conductance regulator (CFTR) by increasing its interaction with the
      C terminus of Hsp70-interacting protein and promoting CFTR ubiquitylation.
AB  - Cysteine string protein (Csp) is a J-domain-containing protein whose
      overexpression blocks the exit of cystic fibrosis transmembrane conductance
      regulator (CFTR) from the endoplasmic reticulum (ER). Another method of blocking
      ER exit, the overexpression of Sar1-GTP, however, yielded twice as much immature
      CFTR compared with Csp overexpression. This finding suggested that Csp not only
      inhibits CFTR ER exit but also facilitates the degradation of immature CFTR. This
      was confirmed by treatment with a proteasome inhibitor, which returned the level
      of immature CFTR to that found in cells expressing Sar1-GTP only. CspH43Q, which
      does not interact with Hsc70/Hsp70 efficiently, did not promote CFTR degradation,
      suggesting that the pro-degradative effect of Csp requires Hsc70/Hsp70
      binding/activation. In agreement with this, Csp overexpression increased the
      amount of Hsc70/Hsp70 co-immunoprecipitated with CFTR, whereas overexpression of
      CspH43Q did not. The Hsc70/Hsp70 binding partner C terminus of Hsp70-interacting
      protein (CHIP) can target CFTR for proteasome-mediated degradation. Csp
      overexpression also increased the amount of CHIP co-immunoprecipitated with CFTR.
      In addition, CHIP interacted directly with Csp, which was confirmed by in vitro
      binding experiments. Csp overexpression also increased CFTR ubiquitylation and
      reduced the half-life of immature CFTR. These findings indicate that Csp not only
      regulates the exit of CFTR from the ER, but that this action is accompanied by
      Hsc70/Hsp70 and CHIP-mediated CFTR degradation.

PMID- 19098310
TI  - Cyst formation in kidney via B-Raf signaling in the PKD2 transgenic mice.
AB  - The pathogenic mechanisms of human autosomal dominant polycystic kidney disease
      (ADPKD) have been well known to include the mutational inactivation of PKD2.
      Although haploinsufficiency and loss of heterozygosity at the Pkd2 locus can
      cause cyst formation in mice, polycystin-2 is frequently expressed in the renal
      cyst of human ADPKD, raising the possibility that deregulated activation of PKD2
      may be associated with the cystogenesis of human ADPKD. To determine whether
      increased PKD2 expression is physiologically pathogenic, we generated PKD2
      overexpressing transgenic mice. These mice developed typical renal cysts and an
      increase of proliferation and apoptosis, which are reflective of the human ADPKD
      phenotype. These manifestations were first observed at six months, and progressed
      with age. In addition, we found that ERK activation was induced by PKD2
      overexpression via B-Raf signaling, providing a possible molecular mechanism of
      cystogenesis. In PKD2 transgenic mice, B-Raf/MEK/ERK sequential signaling was up
      regulated. Additionally, the transgenic human polycystin-2 partially rescues the
      lethality of Pkd2 knock-out mice and therefore demonstrates that the transgene
      generated a functional product. Functional strengthening or deregulated
      activation of PKD2 may be a direct cause of ADPKD. The present study provides
      evidence for an in vivo role of overexpressed PKD2 in cyst formation. This
      transgenic mouse model should provide new insights into the pathogenic mechanism
      of human ADPKD.

PMID- 19098311
TI  - TATA-binding protein variants that bypass the requirement for Mot1 in vivo.
AB  - Mot1 is an essential TATA-binding protein (TBP)-associated factor and Snf2/Swi2
      ATPase that both represses and activates transcription. Biochemical and
      structural results support a model in which ATP binding and hydrolysis induce a
      conformational change in Mot1 that drives local translocation along DNA, thus
      removing TBP. Although this activity explains transcriptional repression, it does
      not as easily explain Mot1-mediated transcriptional activation, and several
      different models have been proposed to explain how Mot1 activates transcription.
      To better understand the function of Mot1 in yeast cells in vivo, particularly
      with regard to gene activation, TBP mutants were identified that bypass the
      requirement for Mot1 in vivo. Although TBP has been extensively mutated and
      analyzed previously, this screen uncovered two novel TBP variants that are unique
      in their ability to bypass the requirement for Mot1. Surprisingly, in vitro
      analyses reveal that rather than having acquired an improved biochemical
      activity, one of the TBPs was defective for interaction with polymerase II
      preinitiation complex (PIC) components and other regulators of TBP function. The
      other mutant was defective for DNA binding in vitro yet was still recruited to
      chromatin in vivo. These results suggest that Mot1-mediated dissociation of TBP
      (or TBP-containing complexes) from chromatin can explain the Mot1 activation
      mechanism at some promoters. The results also suggest that PICs can be
      dynamically unstable and that appropriate PIC instability is critical for the
      regulation of transcription in vivo.

PMID- 19098312
TI  - HMG-CoA reductase inhibitors (statin) prevents retinal neovascularization in a
      model of oxygen-induced retinopathy.
AB  - PURPOSE: Retinal neovascularization (RNV) is a primary cause of blindness and
      involves the dysfunction of retinal capillaries. Recent studies have emphasized
      the beneficial effects of inhibitors of HMG-CoA reductase (statins) in preventing
      vascular dysfunction. In the present study, the authors characterized the
      therapeutic effects of statins on RNV. METHODS: Statin treatment (10 mg/kg/d
      fluvastatin) was tested in a mouse model of oxygen-induced retinopathy.
      Morphometric analysis was conducted to determine the extent of capillary growth.
      Pimonidazole hydrochloride was used to assess retinal ischemia. Western blot and
      immunohistochemical analyses were used to assess protein expression levels and
      immunolocalization. Lipid peroxidation and superoxide radical formation were
      determined to assess oxidative changes. RESULTS: Fluvastatin treatment
      significantly reduced the area of the capillary-free zone (P < 0.01), decreased
      the formation of neovascular tufts (P < 0.01), and ameliorated retinal ischemia.
      These morphologic and functional changes were associated with statin effects in
      preventing the upregulation of VEGF, HIF-1 alpha, phosphorylated STAT3, and
      vascular expression of the inflammatory mediator ICAM-1 (P < 0.01). Superoxide
      production and lipid peroxidation in the ischemic retina were also reduced by
      statin treatment (P < 0.01). CONCLUSIONS: These data suggest the beneficial
      effects of statin treatment in preventing retinal neovascularization. These
      beneficial effects appear to result from the anti-oxidant and anti-inflammatory
      properties of statins.

PMID- 19098313
TI  - Predicting visual sensitivity in retinal prosthesis patients.
AB  - PURPOSE: With the long-term goal of restoring functional vision in patients with
      retinal degenerative diseases, the eyes of blind human subjects were implanted
      chronically with epiretinal prostheses consisting of two-dimensional electrode
      arrays that directly stimulated cells of the neural retina. METHODS:
      Psychophysical techniques were used to measure the brightness of electrically
      generated percepts on single electrodes using a variety of electrical stimulation
      patterns. RESULTS: It was possible to predict the sensitivity of the human visual
      system to a wide variety of retinal electrical stimulation patterns using a
      simple and biologically plausible model. CONCLUSIONS: This is the first study to
      demonstrate that, on the single-electrode level, retinal electrical stimulation
      in humans can produce visual qualia that are predictable using a quantitative
      model, a prerequisite for a successful retinal prosthesis. (ClinicalTrials.gov
      number, NCT00279500.).

PMID- 19098314
TI  - Development of predictive models of proliferative vitreoretinopathy based on
      genetic variables: the Retina 4 project.
AB  - PURPOSE: Machine learning techniques were used to identify which of 14 algorithms
      best predicts the genetic risk for development of proliferative vitreoretinopathy
      (PVR) in patients who are experiencing primary rhegmatogenous retinal detachment
      (RD). METHOD: Data from a total of 196 single nucleotide polymorphisms in 30
      candidate genes were used. The genotypic profile of 138 patients with PVR
      following primary rhegmatogenous RD and 312 patients without PVR RD were
      analyzed. Machine learning techniques were used to develop statistical predictive
      models. Fourteen models were assessed. Their reproducibility was evaluated by an
      internal cross-validation method. RESULTS: The three best predictive models were
      the lineal kernel based on the Support Vector Machine (SMV), the radial kernel
      based on the SVM, and the Random Forest. Accuracy values were 78.4%, 70.3%, and
      69.3%, respectively. The more accurate, although complex, algorithm uses 42 SNPs,
      whereas the simpler one uses only two SNPs, which makes them more suitable for
      routine diagnostic work. The radial kernel based on SVM uses 10 SNPs. The best
      individually predictor marker was rs2229094 in the tumor necrosis factor locus.
      CONCLUSION: Genetic variables may be useful to predict the likelihood of the
      development of PVR. The predictive capabilities of these models are as good as
      those observed with clinical approaches. These results need external validation
      to estimate the true predictive capability and select the most appropriate ones
      for clinical use.

PMID- 19098315
TI  - Potential for transcriptional upregulation of cochlin in glaucomatous trabecular
      meshwork: a combinatorial bioinformatic and biochemical analytical approach.
AB  - PURPOSE: To determine the existence of a relatively higher abundance of potential
      TFs in glaucomatous trabecular meshwork (TM) that may bind putative promoter
      regions and affect cochlin protein expression in glaucomatous compared to normal
      TM. METHODS: Combinatorial bioinformatics and biochemical analyses, using human
      glaucomatous and normal donor tissue (n = 4 each). Biochemical analysis included
      electrophoretic mobility shift assays (EMSAs), filter binding assays (FBAs),
      coupled in vitro transcription-translation (TNT) assays and promoter mutation
      analysis. RESULTS: Combinatorial bioinformatics and biochemical analyses revealed
      the existence of a higher abundance of TFs in glaucomatous than in normal TM
      nuclear extracts. The evidence of a relatively high abundance of TFs, leading to
      increased expression of cochlin predicted by bioinformatic and biochemical
      analyses (EMSA and FBA), was further supported by TNT and promoter mutation TNT
      assays. CONCLUSIONS: These results support the finding that the observed
      increased cochlin expression in glaucomatous TM is due to relative elevated
      abundance of TFs. The results also demonstrate the utility of combinatorial
      bioinformatic and biochemical analyses for genes with uncharacterized promoter
      regions.

PMID- 19098316
TI  - Purification and characterization of mouse lacrimal gland epithelial cells and
      reconstruction of an acinarlike structure in three-dimensional culture.
AB  - PURPOSE: To clarify which factors are involved in postnatal lacrimal gland
      development, the expressions of several growth factors and their receptors were
      analyzed in purified lacrimal gland epithelial and mesenchymal cells.
      Reconstruction of acinarlike structures in three-dimensional culture conditions
      from this epithelial cell population was attempted. METHODS: Lacrimal gland
      epithelial and mesenchymal cells were isolated from newborn mice and purified
      using nylon mesh and collagenase. By real-time reverse transcription-polymerase
      chain reaction, immunocytochemistry, and Western blotting, the expressions of
      several growth factors and their receptors were analyzed. Responses of epithelial
      cells to the growth factors were analyzed by the addition of these factors to the
      culture medium. RESULTS: Fibroblast growth factor (FGF)10 and hepatocyte growth
      factor (HGF) were more intensely expressed in mesenchymal cells than in
      epithelial cells, and their receptors (FGFR2IIIb and c-Met, respectively) were
      less intensely expressed, whereas the expression of epidermal growth factor (EGF)
      and its receptor showed no significant difference between cell types. In the
      monolayer culture, cell viability was activated by the addition of EGF or HGF to
      epithelial cells, but no response was observed when FGF10 was added. The
      epithelial cells formed clusters with lumina when cultured on basement membrane
      matrix. These clusters contained secretion granules and showed positive
      immunostaining for aquaporin-5. CONCLUSIONS: EGF and HGF were considered to act
      in an autocrine/paracrine manner in and around the postnatal lacrimal gland,
      whereas epithelial cells did not respond to FGF10. It was suggested that certain
      extracellular matrix conditions accommodate these epithelial cells to reconstruct
      functional acinarlike structures.

PMID- 19098317
TI  - Role of PI3K/Akt and MEK/ERK in mediating hypoxia-induced expression of HIF
      1alpha and VEGF in laser-induced rat choroidal neovascularization.
AB  - PURPOSE: The transcription factor hypoxia-inducible factor (HIF)-1 plays a
      central physiological role in oxygen and energy homeostasis and is activated
      during hypoxia by stabilization of the subunit HIF-1alpha. Hypoxia plays an
      important role in the development of choroidal neovascularization (CNV).
      Expression of HIF-1alpha has been demonstrated in CNV. Vascular endothelial
      growth factor (VEGF) is one of the most well-characterized angiogenic factors in
      CNV, which is under the regulation of HIF-1. The aim of the present study was to
      explore the upstream signaling pathways involved in regulating hypoxia-induced
      expression of HIF-1alpha and VEGF in laser-induced rat CNV. METHODS: A well
      established rat model of CNV and cultured human retinal pigment epithelium (hRPE)
      was used to investigate the role of PI3K/Akt and MEK/ERK pathways in regulating
      HIF-1alpha and VEGF expression in CNV in rat and hRPE under hypoxia by
      immunohistochemistry, Western blot analysis, real-time PCR, and ELISA. RESULTS:
      pAkt, pERK, HIF-1alpha, and VEGF were upregulated in vivo and in vitro. PI3K
      inhibitor (Ly294002) significantly decreased pAkt activity and HIF-1alpha and
      VEGF expression in vivo and in vitro, whereas MEK inhibitor (PD98059) reduced ERK
      phosphorylation and the expression of VEGF but had no effect on HIF-1alpha.
      LY294002 and PD98059 severely inhibited the formation of CNV. CONCLUSIONS: The
      PI3K/Akt pathway was required for hypoxia-induced expression of HIF-1alpha and
      VEGF, whereas the MEK/ERK pathway was required only for VEGF in laser-induced rat
      CNV.

PMID- 19098318
TI  - Evaluation of the X-linked high-grade myopia locus (MYP1) with cone dysfunction
      and color vision deficiencies.
AB  - PURPOSE: X-linked high myopia with mild cone dysfunction and color vision defects
      has been mapped to chromosome Xq28 (MYP1 locus). CXorf2/TEX28 is a nested,
      intercalated gene within the red-green opsin cone pigment gene tandem array on
      Xq28. The authors investigated whether TEX28 gene alterations were associated
      with the Xq28-linked myopia phenotype. Genomic DNA from five pedigrees (with high
      myopia and either protanopia or deuteranopia) that mapped to Xq28 were screened
      for TEX28 copy number variations (CNVs) and sequence variants. METHODS: To
      examine for CNVs, ultra-high resolution array-comparative genomic hybridization
      (array-CGH) assays were performed comparing the subject genomic DNA with control
      samples (two pairs from two pedigrees). Opsin or TEX28 gene-targeted quantitative
      real-time gene expression assays (comparative CT method) were performed to
      validate the array-CGH findings. All exons of TEX28, including intron/exon
      boundaries, were amplified and sequenced using standard techniques. RESULTS:
      Array-CGH findings revealed predicted duplications in affected patient samples.
      Although only three copies of TEX28 were previously reported within the opsin
      array, quantitative real-time analysis of the TEX28 targeted assay of affected
      male or carrier female individuals in these pedigrees revealed either fewer (one)
      or more (four or five) copies than did related and control unaffected
      individuals. Sequence analysis of TEX28 did not reveal any variants associated
      with the disease status. CONCLUSIONS: CNVs have been proposed to play a role in
      disease inheritance and susceptibility as they affect gene dosage. TEX28 gene
      CNVs appear to be associated with the MYP1 X-linked myopia phenotypes.

PMID- 19098319
TI  - The distribution, release kinetics, and biocompatibility of triamcinolone
      injected and dispersed in silicone oil.
AB  - PURPOSE: Triamcinolone acetonide (TA) has been proposed as an adjuvant to pars
      plana vitrectomy with silicone oil for the surgical treatment of proliferative
      vitreoretinopathy and proliferative diabetic retinopathy. However, to date no
      data about the distribution and pharmacokinetics of lipophilic TA injected into
      silicone oil have been reported. METHODS: An artificial vitreous space chamber
      was filled with silicone oil. TA was either injected or dispersed into silicone
      oil. TA release using a continuous flow model was measured
      spectrophotometrically. To determine the antiproliferative or cytotoxic effect of
      the released TA, monolayer cultures of retinal pigment epithelial cells (ARPE19)
      and retinal ganglion cells (RGC5) were used. Bromodeoxyuridine incorporation, MTT
      assay, and scanning electron microscopy were performed. RESULTS: Injected TA sank
      slowly through the silicone oil and started to sediment below the silicone oil
      bubble shortly after injection. After the simulated intravitreal injection, no TA
      could be retrieved from the silicone oil bubble. In contrast, when a suspension
      of silicone oil and TA was prepared before injection, stable noncytotoxic amounts
      of TA (25 microg/mL) could be retrieved for up to 90 days. After mere injection
      (without previous suspension in silicone oil), the sedimented TA crystals showed
      a pronounced cytotoxic effect. CONCLUSIONS: Intravitreally injected TA does not
      mix with silicone oil. TA crystals that sediment at the lower border of a
      silicone oil bubble may be harmful to retinal cells. A suspension of TA in
      silicone oil may exhibit safer extended release over several days.

PMID- 19098320
TI  - Poly(ADP-ribose)polymerase inhibition counteracts cataract formation and early
      retinal changes in streptozotocin-diabetic rats.
AB  - PURPOSE: This study evaluated the role for poly(ADP-ribose) polymerase (PARP) in
      diabetes-induced cataractogenesis and early retinal changes. METHODS: Control and
      streptozotocin (STZ)-diabetic rats were treated with or without the PARP
      inhibitors 1,5-isoquinolinediol (ISO; 3 mg kg(-1) d(-1) intraperitoneally) and 10
      (4-methyl-piperazin-1-ylmethyl)-2H-7-oxa-1,2-diaza-benzo[de]anthracen-3-1 (GPI
      15427, 30 mg kg(-1) d(-1) orally) for 10 weeks after the first 2 weeks without
      treatment. Lens clarity was evaluated by indirect ophthalmoscopy and slit lamp
      examination, and retinal changes were evaluated by immunohistochemistry and
      Western blot analysis. In in vitro studies, cultured human lens epithelial cells
      and bovine retinal pericytes and endothelial cells were exposed to high glucose
      or palmitate. RESULTS: PARP is expressed in lens, and poly(ADP-ribosyl)ated
      proteins are primarily localized in the 38- to 87-kDa range of the protein
      spectrum, with several minor bands at 17 to 38 kDa. The 38- to 87-kDa and the 17-
      to 38-kDa poly(ADP-ribosyl)ated protein expression increased by 74% and 275%,
      respectively, after 4 weeks of diabetes and by approximately 65% early after
      exposure of lens epithelial cells to 30 mM glucose. Both PARP inhibitors delayed,
      but did not prevent, the formation of diabetic cataract. The number of TUNEL
      positive nuclei in flatmounted retinas increased approximately 4-fold in STZ
      diabetic rats, and this increase was prevented by ISO and GPI-15427. Both PARP
      inhibitors reduced diabetes-induced retinal oxidative-nitrosative and endoplasmic
      reticulum stress and glial activation. GPI-15427 (20 microM) prevented oxidative
      nitrosative stress and cell death in palmitate-exposed pericytes and endothelial
      cells. CONCLUSIONS: PARP activation is implicated in the formation of diabetic
      cataract and in early retinal changes. These findings provide a rationale for the
      development of PARP inhibitors for the prevention of diabetic ocular
      complications.

PMID- 19098322
TI  - Incidence of myopia in high school students with and without red-green color
      vision deficiency.
AB  - PURPOSE: To investigate the influence of color vision on myopia development by
      testing refraction error and axial length of the eye for high school students
      with and without color vision deficiency (CVD). METHODS: A school-based cross
      sectional, cluster sample study was conducted to test the color vision and
      refractive error of 16,539 high school students. Students were screened for CVD
      using a pseudoisochromatic plate. CVD was confirmed in students failing the test
      using a Farnsworth-Munsell 100-Hue Test which also served to classify the subtype
      (protan or deutan). Three classmates of each CVD subject, matched in five myopia
      risk factors, were chosen to form the normal color vision (CN) control group.
      Ophthalmic examinations were performed to determine refractive status and axial
      length. RESULTS: Of the students, 309 were found to have red-green CVD and 927
      were selected as the CN control group. The prevalence of myopia in the CVD group
      (45.6%) was significantly lower than that of the CN group (65.8%; P<0.001). The
      CVD group was also less myopic in refraction (P<0.001) than CN, and protan
      subjects had shorter axial lengths than those in the control group (P=0.007).
      CONCLUSIONS: Color vision deficiencies appear to influence the development of
      myopia. The observed lower incidence of myopia in people with CVD may be linked
      to the reduced functionality of the L/M chromatic mechanism.

PMID- 19098321
TI  - Nucleotide oligomerization domain-2 (NOD2)-induced uveitis: dependence on IFN
      gamma.
AB  - PURPOSE: Nucleotide oligomerization domain-2 (NOD2) plays an important role in
      innate immunity to sense muramyl dipeptide (MDP), a component of bacterial cell
      walls. Notably, NOD2 is linked to eye inflammation because mutations in NOD2
      cause a granulomatous type of uveitis called Blau syndrome. A mouse model of NOD2
      dependent ocular inflammation was employed to test the role of a cytokine
      strongly implicated in granuloma formation, IFN-gamma, in order to gain insight
      into downstream functional consequences of NOD2 activation within the eye
      triggering uveitis. METHODS: Mice deficient in IFN-gamma, NOD2, or CD11b and
      their wild-type controls were treated with intravitreal injection of MDP in the
      presence or absence of IFN-gamma. IFN-gamma production in the eye was measured by
      ELISA. The intravascular inflammatory response within the iris was quantified by
      intravital microscopy. RESULTS: NOD2 activation resulted in the production of IFN
      gamma within the eye. Deficiency in IFN-gamma diminished the development of MDP
      induced uveitis, indicating its crucial role in downstream inflammatory events
      triggered by NOD2. Moreover, exogenous IFN-gamma markedly exacerbated MDP-induced
      ocular inflammation in a NOD2-dependent mechanism. The potential of IFN-gamma to
      enhance inflammation required the adhesion molecule CD11b because CD11b-deficient
      mice failed to show the synergistic effects of IFN-gamma and MDP cotreatment on
      adhering and infiltrating cells. CONCLUSIONS: IFN-gamma was identified as a
      downstream mediator of NOD2-driven inflammation and the capacity of IFN-gamma in
      vivo to enhance the inflammatory potential of NOD2 was demonstrated.
      Extrapolation of these findings in mice suggests that the dysregulation of IFN
      gamma may occur in patients with Blau syndrome, thereby contributing to the
      granulomatous nature of the disease.

PMID- 19098323
TI  - Disparity tuning of binocular facilitation and suppression after normal versus
      abnormal visual development.
AB  - PURPOSE: To study the pattern of facilitatory and suppressive binocular
      interactions in stereodeficient patients with strabismus and in healthy controls.
      METHODS: Visual evoked potentials were recorded in response to a Vernier
      onset/offset pattern presented to one eye, either monocularly or paired
      dichoptically with a straight vertical square-wave grating, which, when fused
      with the target in the other eye, gave rise to a percept of a series of bands
      appearing in depth from an otherwise uniform plane or with a grating that
      contained offsets that produced a standing disparity and the appearance of a
      constantly segmented image, portions of which moved in depth. RESULTS:
      Participants with normal stereopsis showed facilitative and suppressive binocular
      interactions that depended on which dichoptic target was presented. Patients with
      longstanding, constant strabismus lacked normal facilitative binocular
      interactions. The response to a normally facilitative stimulus was reduced below
      the monocular level when it was presented to the dominant eye of patients without
      anisometropia, consistent with classical strabismic suppression of the
      nondominant eye. The dominant eye of strabismic patients without anisometropia
      retained suppressive input from crossed but not uncrossed disparity stimuli
      presented to the nondominant eye. CONCLUSIONS: Abnormal disparity processing can
      be detected with the dichoptic VEP method we describe. Our results suggest that
      suppression in stereoblind, nonamblyopic observers is determined by a binocular
      mechanism responsive to disparity. In some cases, the sign of the disparity is
      important, and this suggests a mechanism that can explain diplopia in patients
      made exotropic after surgery for esotropia.

PMID- 19098324
TI  - Association of optic disc size with development and prognosis of Leber's
      hereditary optic neuropathy.
AB  - PURPOSE: To study the optic nerve head (ONH) morphology of patients with Leber's
      hereditary optic neuropathy (LHON) in a large family from Brazil carrying the
      11778/ND4 mutation and in a case series of unrelated Italian families bearing
      different mitochondrial DNA (mtDNA) pathogenic mutations. METHODS: Enrolled in
      the study were 15 LHON-affected patients (LHON-affected) and 45 LHON unaffected
      mutation carriers (LHON carriers) belonging to the previously reported Brazilian
      SOA-BR LHON pedigree and 56 LHON-affected and 101 LHON carriers from 45 unrelated
      LHON Italian pedigrees molecularly defined. The LHON-affected were subgrouped
      according to the extent of visual recovery. All individuals underwent optic nerve
      head (ONH) analysis by optical coherence tomography. RESULTS: In the Brazilian
      sample, the mean optic disc area was significantly larger in LHON carriers than
      in the control group (P=0.002). In the Italian sample, the mean optic disc area
      and vertical disc diameter were significantly higher in LHON carriers than in
      both LHON-affected (respectively, P=0.008 and P<0.001) and control subjects
      (P<0.001 in both cases). The LHON-affected with visual recovery had a
      significantly larger vertical disc diameter when compared with those without
      visual recovery (P=0.03). CONCLUSIONS: The results, revealing that the ONH size
      is larger in LHON carriers than in LHON-affected, suggest a protective role for
      this anatomic trait. Such a hypothesis is reinforced by the observation that,
      among the LHON-affected, larger discs correlated with visual recovery and better
      visual outcome. The findings may be relevant for prognosis and provide a
      mechanism for identifying nuclear-modifying genes implicated in the variability
      of penetrance in LHON.

PMID- 19098325
TI  - SB-431542 inhibition of scar formation after filtration surgery and its potential
      mechanism.
AB  - PURPOSE: To explore the inhibitive effect of SB-431542 (an ALK5 inhibitor) on
      scar formation after glaucoma surgery and to identify the potential pharmacologic
      target(s). METHODS: Twenty-four New Zealand rabbits underwent filtration surgery
      on the right eye and were divided into a control group and three experimental
      groups (n=6). Human Tenon's fibroblast monolayer was scraped to generate a single
      gap, and then the control medium with SB-431542 only or containing 10 microg/L
      TGF-beta1 and SB-431542 (1-20 microM) was added. The cells were pretreated with
      SB-431542 or in control medium for 30 minutes before induction with 10 microg/L
      TGF-beta1 or 1 microg/L TGF-beta2. The expression of alpha-SM-actin, CTGF, and
      Col I, as well as changes in the Smad, ERK, P38, and AKT signaling pathways were
      detected. RESULTS: In comparison with the control rabbits, the IOPs in the
      experimental groups remained at lower levels until day 25 (P<0.05) after the
      surgery. Histologic profiles showed that there was only a mild deposition of
      collagen in the subconjunctival space in the experimental groups. The cell growth
      and migration were inhibited effectively by SB-431542, regardless of whether TGF
      beta was present in the culture system. SB-431542 abrogated TGF-beta-induced
      upregulation of alpha-SM-actin, CTGF, and Col I. It effectively inhibited the
      phosphorylation of Smad2 stimulated by TGF-beta but not that of the components of
      the MAPK pathways. CONCLUSIONS: SB-431542 inhibits scar formation after glaucoma
      filtration surgery. The mechanism may be that SB-431542 interferes in the
      phosphorylation of Smad2, thus abrogating TGF-beta-induced fibroblast
      transdifferentiation and then decreasing Col I synthesis.

PMID- 19098326
TI  - Role of the aquaporin PIP1 subfamily in the chilling tolerance of rice.
AB  - Although an association between chilling tolerance and aquaporins has been
      reported, the exact mechanisms involved in this relationship remain unclear. We
      compared the expression profiles of aquaporin genes between a chilling-tolerant
      and a low temperature-sensitive rice variety using real-time PCR and identified
      seven genes that closely correlated with chilling tolerance. Chemical treatment
      experiments, by which rice plants were induced to lose their chilling tolerance,
      implicated the PIP1 (plasma membrane intrinsic protein 1) subfamily member genes
      in chilling tolerance. Of these members, changes in expression of the OsPIP1;3
      gene suggested this to be the most closely related to chilling tolerance.
      Although OsPIP1;3 showed a much lower water permeability than members of the
      OsPIP2 family, OsPIP1;3 enhanced the water permeability of OsPIP2;2 and OsPIP2;4
      when co-expressed with either of these proteins in oocytes. Transgenic rice
      plants (OE1) overexpressing OsPIP1;3 showed an enhanced level of chilling
      tolerance and the ability to maintain high OsPIP1;3 expression levels under low
      temperature treatment, similar to that of chilling-tolerant rice plants. We
      assume that OsPIP1;3, constitutively overexpressed in the leaf and root of
      transgenic OE1 plants, interacts with members of the OsPIP2 subfamily, thereby
      improving the plants' water balance under low temperatures and resulting in the
      observed chilling tolerance of the plants.

PMID- 19098327
TI  - Stent fracture: a biomaterial scientist's responsibility or an interventionist's
      onus?

PMID- 19098328
TI  - Rheumatic heart disease: is it declining in India?

PMID- 19098329
TI  - Transient left ventricular apical ballooning--a novel acute cardiac syndrome.

PMID- 19098330
TI  - Continued popularity of metabolic syndrome as an entity and need for waist
      circumference measurement.

PMID- 19098332
TI  - Emerging risk factors for atherosclerosis.

PMID- 19098331
TI  - Outcomes of off-pump coronary artery bypass surgery: current best available
      evidence.
AB  - In the last decade, there has been an upsurge of interest in less invasive
      alternatives to standard coronary artery bypass grafting performed with
      cardiopulmonary bypass. Off-pump coronary artery bypass grafting is one such less
      invasive alternative that has seen a resurgence in the last 10 years. The
      development and application of the technology required has largely been driven by
      the hope of decreasing the incidence and/or severity of the adverse outcomes
      associated with cardiopulmonary bypass, the idea being to perform coronary artery
      bypass grafting without cardiopulmonary bypass. A number of studies that have
      reported the safety and efficacy of off-pump coronary artery bypass surgery have
      provided the impetus for the development of this technology over the last decade.
      Despite tremendous enthusiasm on the part of cardiac surgeons, patients, industry
      and the media, skepticism still exists about the actual impact of off-pump
      coronary artery bypass grafting on the outcomes after coronary artery bypass
      grafting. The only means of countering this skepticism is to validate the safety
      and efficacy of off-pump coronary artery bypass surgery through the explicit and
      conscientious assessment of current best evidence. This review article attempts
      to evaluate the current best evidence available from randomized, controlled
      trials in order to compare the outcomes of off-pump coronary artery bypass
      surgery and conventional coronary artery bypass grafting.

PMID- 19098333
TI  - Serum levels of selenium, zinc and copper in patients with coronary artery
      ectasia.
AB  - BACKGROUND: It is well established that the deficiency of trace elements may lead
      to oxidative stress in many tissues. Several studies have shown that the
      deficiency of trace elements may play a role in the pathogenesis of various heart
      diseases, including coronary artery disease. This study was designed to determine
      the serum levels of trace elements, such as selenium, zinc, and copper, in
      patients with isolated coronary artery ectasia and to confirm previously
      documented changes in the trace element status in coronary artery disease. It
      also investigated the relationship between the level of trace elements and the
      extent of ectatic involvement in patients of coronary artery ectasia. METHODS AND
      RESULTS: The serum selenium, zinc and copper levels were measured in 37 patients
      of coronary artery ectasia, 56 patients of coronary artery disease and 30
      controls. The trace element levels were measured by atomic absorption photometry
      methods. The serum selenium (Se) and zinc (Zn) levels in both sets of patients
      were significantly lower than in the control group (Se: 127 +/- 10 microg/L and
      126 +/- 9 microg/L vs. 147 +/- 12 microg/L, p < 0.001; Zn: 557 +/- 11 microg/L
      and 554 +/- 13 microg/L vs. 620 +/- 13 microg/L, p < 0.001). However, the serum
      copper (Cu) levels were similar in all patients and controls (964 +/- 12 microg/L
      and 973 +/- 14 microg/L vs. 956 +/- 17 microg7/L, p > 0.05). CONCLUSION: These
      results suggest that coronary artery ectasia is associated with the deficiency of
      the trace elements selenium and zinc. Thus, these elements may play an important
      role in the pathogenesis of coronary artery ectasia, as well as in coronary
      artery disease.

PMID- 19098334
TI  - Prevalence of coronary heart disease in Kashmiris.
AB  - Coronary Heart Disease (CHD) is one of the major causes of mortality and
      morbidity in the general population of both the developing and developed
      countries. Prevalence of CHD in the Indian subcontinent is presently one of the
      highest and is further on an increase. In the state of Jammu and Kashmir the
      population like any other developing community, is undergoing lifestyle changes
      but the unusual stress and strain for the last 15 years of the disturbed
      situation in the state apparently has contributed to increase the prevalence of
      CHD. Therefore an epidemiological study was conducted to assess the prevalence of
      CHD in both rural and urban areas of the valley. This study was carried out in
      the rural and urban areas of the twin districts of Anantnag and Srinagar by
      random sampling. The total population of the study area comprised of 44,305
      persons out of which the target population was 13,893. The study was carried out
      on 3128 (23%) subjects (2284 males and 844 females) aged 40 years and above. In
      rural areas the study was conducted in a cluster of 3 villages in each district
      on 1552 persons (1088 males and 464 females) and in urban areas it was carried
      out in 3 mohallas (closed locality) in each district on 1576 persons (1196 males
      and 380 females). A complete history and clinical examination was done and Rose
      Questionnaire was recorded for angina. ECG was done in all subjects. Chi square
      test was used for statistical analysis. The overall prevalence of CHD in the
      population studied by all diagnostic measures was 7.54%. The overall rural
      prevalence was 6.70% and urban prevalence was 8.37%. Prevalence of CHD was higher
      in males, 7.88% and slightly lower in females, 6.63%.

PMID- 19098335
TI  - Prevalence of rheumatic heart disease in school-going children of Eastern Uttar
      Pradesh.
AB  - BACKGROUND: Rheumatic heart disease is a major health problem in our country.
      There is evidence from South India that its prevalence is declining. This study
      attempts to confirm whether this is so in North India as well. METHODS AND
      RESULTS: A total of 118,212 (68,357 males, 49,855 females) schoolchildren in the
      age group of 4-18 years were examined for the presence of heart disease.
      Evaluation, including echocardiography, confirmed that of a total of 389
      suspected to have heart disease, 61 had rheumatic heart disease. Thus, the
      prevalence of rheumatic heart disease was found to be approximately 0.5 per 1000
      children. CONCLUSION: In a fairly large school survey conducted by us, the
      prevalence of rheumatic heart disease turned out to be approximately 0.5 per 1000
      children. This is the lowest figure reported from our country so far and confirms
      the decline of this disease in our country.

PMID- 19098336
TI  - Association of carotid intima-media thickness with left main coronary artery
      disease.
AB  - BACKGROUND: Previous studies have shown that carotid intima-media thickness
      correlates well with the presence and extent of coronary artery disease. This
      study was conducted to determine whether it could reliably predict the presence
      of left main coronary artery disease. METHODS: Common carotid intima-media
      thickness was measured in 50 patients with angiographically proven significant (>
      or =50%stenosis) left main coronary artery disease and in another 50 age- and sex
      matched patients with coronary artery disease without the involvement of the left
      main coronary artery. Measurements of the carotid intima-media thickness were
      made on the far wall 1 cm from the distal end of the common carotid artery
      bilaterally, and the average and the greater of the two values thus obtained for
      each patient were used for analysis. Plaques were not included in the measurement
      of carotid intima-media thickness. RESULTS: The average and greater of the two
      values were significantly higher in patients with left main coronary artery
      disease as compared to those without it (average intima-media thickness: 0.926 +/
      0.12 vs. 0.78 9 +/- 0.16 mm; p< 0.001; greater intima-media thickness: 0.994 +/-
      0.13 vs. 0.844 +/- 0.20 mm; p< 0.001). The cut-off values of 0.81 mm for the
      average carotid intima-media thickness and 0.87 mm for the greater carotid intima
      media thickness were found to have optimum sensitivity (92% and 90%,
      respectively) and specificity (60% and 64%, respectively) for the detection of
      left main coronary artery disease. A higher cut-off value of 1.0 mm increased
      specificity to 92% and 84%, respectively, for the average and greater
      thicknesses, but sensitivity decreased markedly. CONCLUSIONS: There is a
      significant association between increased carotid intima-media thickness and the
      presence of left main coronary artery disease. The measurement of carotid intima
      media thickness can be used with reasonably good sensitivity and specificity for
      the detection of left main coronary artery disease in patients who are undergoing
      evaluation for suspectedcoronary artery disease.

PMID- 19098337
TI  - Potbelly--the most powerful predictor of metabolic syndrome and premature
      morbidity and mortality.
AB  - BACKGROUND: We evaluated the hospital population for the prevalence of the
      metabolic syndrome with the help of clinical variables, such as abdominal waist
      circumference, biochemical variables and ultrasonic variables. The aim was to
      define the most sensitive and powerful predictor of the syndrome, as also of
      premature morbidity and mortality. METHODS: We used clinical and biochemical data
      from our prospective study: "To Evaluate the Scenario of Metabolic Syndrome in
      the Hospital-Based Community". The criteria used for the definition of the
      syndrome were those laid down by the National Cholesterol Eradication Program
      Adult Treatment Panel III. The modified criteria for Asian Indians, that is, an
      abdominal waist circumference of greater than 90 cm in men, and above 80 cm in
      women, were also included. A total of 200 patients (100 males and 100 females)
      between the ages of 20 and 85 years were clinically and biochemically evaluated
      for the study. RESULTS: The results using the National Cholesterol Eradication
      Program Adult Treatment Panel III criteria as well as the modified criteria
      showed that abdominal waist circumference is the single most accurate (79% and
      86.5%, respectively) predictor for determining the metabolic status of an
      individual (p-value <0.001). The waist circumference cut-off of the modified
      criteria proved to be a more accurate predictor for males as well as females (69%
      vs. 84%, and 89% vs. 85%, respectively for the two definitions; p-value <0.001).
      CONCLUSIONS: An abdominal girth of above 90 cm in males and above 80 cm in
      females is a far more powerful clinical predictor of the metabolic syndrome than
      other clinical, biochemical and ultrasonic variables (p-value <0.001). This may
      be considered in the context of premature morbidity and mortality.

PMID- 19098338
TI  - Elevated B-type natriuretic peptide level: use with caution in patients with
      multiple co-morbidities and presenting with dyspnea.
AB  - BACKGROUND AND AIM: While the effect of age, gender, body mass index and renal
      failure on B-type natriuretic peptide (BNP) has been studied individually in
      different trials, the influence of all these co-morbidities in patients with
      dyspnea needs to be evaluated. The objective of our study was to examine the
      effect of age, gender, obesity and co-morbid conditions on the evaluation of
      higher BNP levels in patients presenting with dyspnea. METHODS: A total of 382
      patients admitted with shortness of breath and suspected to have congestive heart
      failure were included in the study. The co-morbid conditions studied were
      pulmonary hypertension, pleural effusion, obesity, renal failure and chronic
      obstructive pulmonary disease. RESULTS: The mean BNP levels significantly
      increased with age. Women tended to have slightly higher mean BNP levels than
      men, but the differences were not statistically significant. The body mass index
      had an inverse correlation with the BNP level. Regression analysis demonstrated
      that the most significant predictors of a higher BNP were the lower left
      ventricular ejection fraction (OR 6.2: 95% CI 2.74-14.02), renal failure (OR
      3.88: 95% CI 1.9-7.91) and pulmonary hypertension (OR 2.28: 95% CI 1.14-4.54).
      CONCLUSION: A lower left ventricular ejection fraction, renal failure and
      pulmonary hypertension were the most significant predictors of an increased BNP
      level. Age, gender, obesity and pleural effusion minimally influenced the BNP
      level and were not significantly predictive of congestive heart failure.

PMID- 19098339
TI  - Cardiovascular MRI: what cardiologists need to know.
AB  - During the past decade, cardiovascular magnetic resonance imaging has firmly
      established itself as an important non-invasive imaging technique for
      comprehensive evaluation of cardiovascular diseases. Gradually, this technique
      has become the 'gold standard' for the assessment of numerous cardiovascular
      conditions. Among the important clinical indications assessed by this technique
      are heart failure, ischemic heart disease, cardiac masses, congenital heart
      disease, and diseases of the myocardium, pericardium, valves and the entire
      vascular tree. Continued research and further progress in magnetic resonance
      imaging technology herald an exciting growth of clinical applications, including
      coronary imaging and interventional magnetic resonance imaging.

PMID- 19098340
TI  - Stent fracture after stent therapy for aortic coarctation: nightmares in invasive
      cardiology.

PMID- 19098341
TI  - Electrocardiographic manifestations in a hypothermic patient: review of Osborn
      waves.

PMID- 19098342
TI  - LV apical ballooning syndrome--takotsubo cardiomyopathy.

PMID- 19098343
TI  - Delayed stent fracture and aneurysm formation after sirolimus eluting stent.

PMID- 19098344
TI  - Severe Tako-Tsubo syndrome in the weeks following PCI.

PMID- 19098345
TI  - Rebound thrombocytosis causing MI following dengue fever?

PMID- 19098346
TI  - Patient-doctor partnership: the new ethos of professionalism.

PMID- 19098348
TI  - Aortic involvement in Marfans syndrome.

PMID- 19098349
TI  - Computational estimation of magnetically induced electric fields in a rotating
      head.
AB  - Change in a magnetic field, or similarly, movement in a strong static magnetic
      field induces electric fields in human tissues, which could potentially cause
      harmful effects. In this paper, the fields induced by different rotational
      movements of a head in a strong homogeneous magnetic field are computed
      numerically. Average field magnitudes near the retinas and inner ears are studied
      in order to gain insight into the causes of phosphenes and vertigo-like effects,
      which are associated with extremely low-frequency (ELF) magnetic fields. The
      induced electric fields are calculated in four different anatomically realistic
      head models using an efficient finite-element method (FEM) solver. The results
      are compared with basic restriction limits by IEEE and ICNIRP. Under rotational
      movement of the head, with a magnetic flux rate of change of 1 T s(-1), the
      maximum IEEE-averaged electric field and maximum ICNIRP-averaged current density
      were 337 mV m(-1) and 8.84 mA m(-2), respectively. The limits by IEEE seem
      significantly stricter than those by ICNIRP. The results show that a magnetic
      flux rate of change of 1 T s(-1) may induce electric field in the range of 50 mV
      m(-1) near retinas, and possibly even larger values near the inner ears. These
      results provide information for approximating the threshold electric field values
      of phosphenes and vertigo-like effects.

PMID- 19098350
TI  - Investigation of detection limits for diffuse optical tomography systems: II.
      Analysis of slab and cup geometry for breast imaging.
AB  - Using a statistical (chi-square) test on simulated data and a realistic noise
      model derived from the system's hardware we study the performance of diffuse
      optical tomography systems for fluorescence imaging. We compare the predicted
      smallest size of detectable lesions at various positions in slab and cup geometry
      and model how detection sensitivity depends on breast compression and lesion
      fluorescence contrast. Our investigation shows that lesion detection is limited
      by relative noise in slab geometry and by absolute noise in cup geometry.

PMID- 19098351
TI  - Experimental evaluation of a simple lesion detection task with time-of-flight
      PET.
AB  - A new generation of high-performance, time-of-flight (TOF) PET scanners have
      recently been developed. In earlier works, the gain with TOF information was
      derived as a reduction of noise in the reconstructed image, or essentially a gain
      in scanner sensitivity. These derivations were applicable to analytical
      reconstruction techniques and 2D PET imaging. In this work, we evaluate the gain
      measured in the clinically relevant task of lesion detection with TOF information
      in fully 3D PET scanners using iterative reconstruction algorithms. We performed
      measurements in a fully 3D TOF PET scanner using spherical lesions in uniform,
      cylindrical phantom. Lesion detectability was estimated for 10 mm diameter
      lesions using a non-prewhitening matched filter signal-to-noise-ratio (NPW SNR)
      as the metric. Our results show that the use of TOF information leads to
      increased lesion detectability, which is achieved with less number of iterations
      of the reconstruction algorithm. These phantom results indicate that clinically,
      TOF PET will allow reduced scan times and improved lesion detectability,
      especially in large patients.

PMID- 19098352
TI  - Physical evaluation of prototype high-performance anti-scatter grids: potential
      for improved digital radiographic image quality.
AB  - Grid evaluation for a screen-film x-ray system has typically included independent
      measurement of the opposing contrast improvement factor and Bucky factor. Neither
      of these metrics, however, is appropriate when assessing grid performance in a
      digital imaging environment. For digital radiographic systems, the benefit of an
      anti-scatter grid is well characterized by the quantum signal-to-noise ratio
      improvement factor (K(SNR)) provided by the grid. The purpose of this work was to
      measure K(SNR) of prototype grids designed for use with digital radiographic
      systems. The prototype grids had 5 mm tall lead septa, fiber interspace material,
      line rate N = 25 and 36 cm(-1) and ratio r = 15 and 21, respectively. The primary
      and scatter transmission properties of the grids were measured, and K(SNR) was
      evaluated over a phantom thickness range of 10-50 cm. To provide a comparison,
      the K(SNR) of similarly constructed N44r15 and N80r15 grids is also reported.
      K(SNR) of the prototype grids ranged from 1.4 for the 10 cm phantom to 2.4 for
      the 50 cm phantom. For the thickest phantom, the SNR improvement factor of the
      prototype grids was 18-83% higher than that of the N44r15 and N80r15 grids,
      respectively.

PMID- 19098353
TI  - Clinical implementation of enhanced dynamic wedges into the Pinnacle treatment
      planning system: Monte Carlo validation and patient-specific QA.
AB  - The goal of this work is to present a systematic Monte Carlo validation study on
      the clinical implementation of the enhanced dynamic wedges (EDWs) into the
      Pinnacle(3) (Philips Medical Systems, Fitchburg, WI) treatment planning system
      (TPS) and QA procedures for patient plan verification treated with EDWs. Modeling
      of EDW beams in the Pinnacle(3) TPS, which employs a collapsed-cone convolution
      superposition (CCCS) dose model, was based on a combination of measured open-beam
      data and the 'Golden Segmented Treatment Table' (GSTT) provided by Varian for
      each photon beam energy. To validate EDW models, dose profiles of 6 and 10 MV
      photon beams from a Clinac 2100 C/D were measured in virtual water at depths from
      near-surface to 30 cm for a wide range of field sizes and wedge angles using the
      Profiler 2 (Sun Nuclear Corporation, Melbourne, FL) diode array system. The EDW
      output factors (EDWOFs) for square fields from 4 to 20 cm wide were measured in
      virtual water using a small-volume Farmer-type ionization chamber placed at a
      depth of 10 cm on the central axis. Furthermore, the 6 and 10 MV photon beams
      emerging from the treatment head of Clinac 2100 C/D were fully modeled and the
      central-axis depth doses, the off-axis dose profiles and the output factors in
      water for open and dynamically wedged fields were calculated using the Monte
      Carlo (MC) package EGS4. Our results have shown that (1) both the central-axis
      depth doses and the off-axis dose profiles of various EDWs computed with the CCCS
      dose model and MC simulations showed good agreement with the measurements to
      within 2%/2 mm; (2) measured EDWOFs used for monitor-unit calculation in
      Pinnacle(3) TPS agreed well with the CCCS and MC predictions within 2%; (3) all
      the EDW fields satisfied our validation criteria of 1% relative dose difference
      and 2 mm distance-to-agreement (DTA) with 99-100% passing rate in routine patient
      treatment plan verification using MapCheck 2D diode array.

PMID- 19098354
TI  - Mechanical analysis of congestive heart failure caused by bundle branch block
      based on an electromechanical canine heart model.
AB  - Asynchronous electrical activation, induced by bundle branch block (BBB), can
      cause reduced ventricular function. However, the effects of BBB on the mechanical
      function of heart are difficult to assess experimentally. Many heart models have
      been developed to investigate cardiac properties during BBB but have mainly
      focused on the electrophysiological properties. To date, the mechanical function
      of BBB has not been well investigated. Based on a three-dimensional
      electromechanical canine heart model, the mechanical properties of complete left
      and right bundle branch block (LBBB and RBBB) were simulated. The anatomical
      model as well as the fiber orientations of a dog heart was reconstructed from
      magnetic resonance imaging (MRI) and diffusion tensor MRI (DT-MRI). Using the
      solutions of reaction-diffusion equations and with a strategy of parallel
      computation, the asynchronous excitation propagation and intraventricular
      conduction in BBB was simulated. The mechanics of myocardial tissues were
      computed with time-, sarcomere length-dependent uniaxial active stress initiated
      at the time of depolarization. The quantification of mechanical intra- and
      interventricular asynchrony of BBB was then investigated using the finite-element
      method with an eight-node isoparametric element. The simulation results show that
      (1) there exists inter- and intraventricular systolic dyssynchrony during BBB;
      (2) RBBB may have more mechanical synchrony and better systolic function of the
      left ventricle (LV) than LBBB; (3) the ventricles always move toward the early
      activated ventricle; and (4) the septum experiences higher stress than left and
      right ventricular free walls in BBB. The simulation results validate clinical and
      experimental recordings of heart deformation and provide regional quantitative
      estimates of ventricular wall strain and stress. The present work suggests that
      an electromechanical heart model, incorporating real geometry and fiber
      orientations, may be helpful for better understanding of the mechanical
      implications of congestive heart failure (CHF) caused by BBB.

PMID- 19098355
TI  - Delivery of modulated electron beams with conventional photon multi-leaf
      collimators.
AB  - Electron beam radiotherapy is an accepted method to treat shallow tumors.
      However, modulation of electrons to customize dose distributions has not readily
      been achieved. Studies of bolus and tertiary collimation systems have been met
      with limitations. We pursue the use of photon multi-leaf collimators (MLC) for
      modulated electron radiotherapy (MERT) to achieve customized distributions for
      potential clinical use. As commercial planning systems do not support the use of
      MLC with electrons, planning was conducted using Monte Carlo calculations.
      Segmented and dynamic modulated delivery of multiple electron segments was
      configured, calculated and delivered for validation. Delivery of electrons with
      segmented or dynamic leaf motion was conducted. A phantom possessing an idealized
      stepped target was planned and optimized with subsequent validation by
      measurements. Finally, clinical treatment plans were conducted for post
      mastectomy and cutaneous lymphoma of the scalp using forward optimization
      techniques. Comparison of calculations and measurements was successful with
      agreement of +/-2%/2 mm for the energies, segment sizes, depths tested for
      delivered segments for the dynamic and segmented delivery. Clinical treatment
      plans performed provided optimal dose coverage of the target while sparing distal
      organs at risk. Execution of plans using an anthropomorphic phantom to ensure
      safe and efficient delivery was conducted. Our study validates that MERT is not
      only possible using the photon MLC, but the efficient and safe delivery inherent
      with the dynamic delivery provides an ideal technique for shallow tumor
      treatment.

PMID- 19098356
TI  - Depth of interaction calibration for PET detectors with dual-ended readout by
      PSAPDs.
AB  - Many laboratories develop depth-encoding detectors to improve the trade-off
      between spatial resolution and sensitivity in positron emission tomography (PET)
      scanners. One challenge in implementing these detectors is the need to calibrate
      the depth of interaction (DOI) response for the large numbers of detector
      elements in a scanner. In this work, we evaluate two different methods, a linear
      detector calibration and a linear crystal calibration, for determining DOI
      calibration parameters. Both methods can use measurements from any source
      distribution and location, or even the intrinsic lutetium oxyorthosilicate (LSO)
      background activity, and are therefore well suited for use in a depth-encoding
      PET scanner. The methods were evaluated by measuring detector and crystal DOI
      responses for all eight detectors in a prototype depth-encoding PET scanner. The
      detectors utilize dual-ended readout of LSO scintillator arrays with position
      sensitive avalanche photodiodes (PSAPDs). The LSO arrays have 7 x 7 elements,
      with a crystal size of 0.92 x 0.92 x 20 mm(3) and pitch of 1.0 mm. The arrays are
      read out by two 8 x 8 mm(2) area PSAPDs placed at opposite ends of the arrays.
      DOI is measured by the ratio of the amplitude of the total energy signals
      measured by the two PSAPDs. Small variations were observed in the DOI responses
      of different crystals within an array as well as DOI responses for different
      arrays. A slightly nonlinear dependence of the DOI ratio on depth was observed
      and the nonlinearity was larger for the corner and edge crystals. The DOI
      calibration parameters were obtained from the DOI responses measured in a singles
      mode. The average error between the calibrated DOI and the known DOI was 0.8 mm
      if a linear detector DOI calibration was used and 0.5 mm if a linear crystal DOI
      calibration was used. A line source phantom and a hot rod phantom were scanned on
      the prototype PET scanner. DOI measurement significantly improved the image
      spatial resolution no matter which DOI calibration method was used. A linear
      crystal DOI calibration provided slightly better image spatial resolution
      compared with a linear detector DOI calibration.

PMID- 19098357
TI  - Analysis of dose perturbation factors of a NACP-02 ionization chamber in clinical
      electron beams.
AB  - For well-guarded plane-parallel ionization chambers, international dosimetry
      protocols recommend a value of unity for electron perturbation factors in water.
      However, recent data published by various groups have challenged this.
      Specifically for the NACP-02 chamber, non-unity electron perturbation factors
      have already been published by Verhaegen et al (2006 Phys. Med. Biol. 51 1221-35)
      and Buckley and Rogers (2006 Med. Phys. 33 1788-96). Recently it was found that
      the mass thickness of the front chamber window can be 35% greater than is listed
      in the IAEA's TRS-398 absorbed dose protocol (Chin et al 2008 Phys. Med. Biol. 53
      N119-26). This study therefore recalculated NACP-02 electron perturbation
      correction factors for energies 4-18 MeV at depths z(ref) and R(50) to determine
      the effect of the chamber model change. Results showed that perturbation factors
      at z(ref) are fairly stable for similar chamber models but become highly
      sensitive to small changes at deeper depths. The results also showed some
      dependence on using 1 keV versus 10 keV for the transport cut-off. Additional
      investigations revealed that the wall perturbation factor, p(wall), is strongly
      influenced by the chamber back wall at z(ref) and at larger depths small changes
      in the positioning of the effective point of measurement cause large fluctuations
      in the final value. Finally, the cavity perturbation factor, p(cav), was found to
      be primarily influenced by electron backscatter.

PMID- 19098358
TI  - Trajectory analysis for magnetic particle imaging.
AB  - Recently a new imaging technique called magnetic particle imaging was proposed.
      The method uses the nonlinear response of magnetic nanoparticles when a time
      varying magnetic field is applied. Spatial encoding is achieved by moving a field
      free point through an object of interest while the field strength in the vicinity
      of the point is high. A resolution in the submillimeter range is provided even
      for fast data acquisition sequences. In this paper, a simulation study is
      performed on different trajectories moving the field-free point through the field
      of view. The purpose is to provide mandatory information for the design of a
      magnetic particle imaging scanner. Trajectories are compared with respect to
      density, speed and image quality when applied in data acquisition. Since
      simulation of the involved physics is a time demanding task, moreover, an
      efficient implementation is presented utilizing caching techniques.

PMID- 19098359
TI  - Investigation of detection limits for diffuse optical tomography systems: I.
      Theory and experiment.
AB  - We present a statistical test using simulated photon migration data and a noise
      model derived from the hardware of a particular diffuse optical tomography system
      to predict its detection limits. Our method allows us to assess the spatial
      distribution of the detection sensitivity of arbitrary geometries and noise
      without requiring phantom measurements and reconstructions. We determine the
      minimal detectable lesion size at selected lesion positions and compare the
      predicted results with phantom measurements carried out in a cup geometry.

PMID- 19098360
TI  - Folate and S-adenosylmethionine modulate synaptic activity in cultured cortical
      neurons: acute differential impact on normal and apolipoprotein-deficient mice.
AB  - Folate deficiency is accompanied by a decline in the cognitive neurotransmitter
      acetylcholine and a decline in cognitive performance in mice lacking
      apolipoprotein E (ApoE-/- mice), a low-density lipoprotein that regulates aspects
      of lipid metabolism. One direct consequence of folate deficiency is a decline in
      S-adenosylmethionine (SAM). Since dietary SAM supplementation maintains
      acetylcholine levels and cognitive performance in the absence of folate, we
      examined herein the impact of folate and SAM on neuronal synaptic activity.
      Embryonic cortical neurons from mice expressing or lacking ApoE (ApoE+/+ or -/-,
      respectively) were cultured for 1 month on multi-electrode arrays, and signaling
      was recorded. ApoE+/+ cultures displayed significantly more frequent spontaneous
      signals than ApoE-/- cultures. Supplementation with 166 microm SAM (not normally
      present in culture medium) increased signal frequency and decreased signal
      amplitude in ApoE+/+ cultures. SAM also increased the frequency of tightly
      clustered signal bursts. Folate deprivation reversibly reduced signal frequency
      in ApoE+/+ cultures; SAM supplementation maintained signal frequency despite
      folate deprivation. These findings support the importance of dietary
      supplementation with folate and SAM on neuronal health. Supplementation with 166
      microm SAM did not alter signaling in ApoE-/- cultures, which may be a reflection
      of the reduced SAM levels in ApoE-/- mice. The differential impact of SAM on
      ApoE+/+ and -/- neurons underscores the combined impact of nutritional and
      genetic deficiencies on neuronal homeostasis.

PMID- 19098361
TI  - Functional characteristics of a double positive feedback loop coupled with
      autorepression.
AB  - We study the functional characteristics of a two-gene motif consisting of a
      double positive feedback loop and an autoregulatory negative feedback loop. The
      motif appears in the gene regulatory network controlling the functional activity
      of pancreatic beta-cells. The model exhibits bistability and hysteresis in
      appropriate parameter regions. The two stable steady states correspond to low
      (OFF state) and high (ON state) protein levels, respectively. Using a
      deterministic approach, we show that the region of bistability increases in
      extent when the copy number of one of the genes is reduced from 2 to 1. The
      negative feedback loop has the effect of reducing the size of the bistable
      region. Loss of a gene copy, brought about by mutations, hampers the normal
      functioning of the beta-cells giving rise to the genetic disorder, maturity-onset
      diabetes of the young (MODY). The diabetic phenotype makes its appearance when a
      sizable fraction of the beta-cells is in the OFF state. Using stochastic
      simulation techniques we show that, on reduction of the gene copy number, there
      is a transition from the monostable ON to the ON state in the bistable region of
      the parameter space. Fluctuations in the protein levels, arising due to the
      stochastic nature of gene expression, can give rise to transitions between the ON
      and OFF states. We show that as the strength of autorepression increases, the ON 
      -> OFF state transitions become less probable whereas the reverse transitions are
      more probable. The implications of the results in the context of the occurrence
      of MODY are pointed out.

PMID- 19098362
TI  - Immunologic basis and immunoprophylaxis of RhD induced hemolytic disease of the
      newborn (HDN).
AB  - RhD antigen is the most immunogenic and clinically significant antigen of red
      blood cells after ABO system. It has historically been associated with hemolytic
      disease of the newborn (HDN) which is now routinely prevented by the
      administration of polyclonal anti-D immunoglobulin. This management of HDN has
      proven to be one of the most successful cases of prophylactic treatment based on
      antibody mediated immune suppression (AMIS). Despite the increasing efficiency of
      treatment, the mechanism of action of anti-D is not completely defined. There is
      a widespread interest in obtaining a reliable therapeutic monoclonal anti-D, due
      to difficulty of maintaining a pool of high titer volunteer donors for plasma
      collection and also increasing demand for antenatal prophylaxis and safety issues
      with plasma derived products. Candidate monoclonal anti-D preparations should
      demonstrate appropriate functionality in both in vitro and in vivo assays
      comparable to polyclonal anti-D immunoglobulin. These criteria are reviewed in
      addition to the factors regulating development of D specific immune response in D
      negative individuals and its suppression in HDN prophylaxis.

PMID- 19098363
TI  - Association of CCR5-59029 A/G and CCR2-V64I variants with renal allograft
      survival.
AB  - BACKGROUND: Despite advances in the medical care of renal transplant recipients
      which have led to an improvement in allograft survival, renal allograft rejection
      is still a major obstacle to successful organ transplantation. Understanding the
      mechanisms contributing to allograft rejection will be of great importance for
      the development of efficient antirejection strategies. OBJECTIVE: The aim of
      current investigation was to study the impact of polymorphisms of CCR5Delta32,
      CCR5- 59029 A/G and CCR2-V64I on renal allograft survival. METHODS: Using PCR and
      PCR-RFLP methods in 84 renal transplant recipients, the influence of CCR5Delta32,
      CCR5- 59029 A/G and CCR2-V64I polymorphisms on renal allograft survival in two
      rejector and non-rejector groups were examined. Rejector group was defined as
      having rejection before 1 year and non-rejector group had stable graft function
      at least for 5 years. RESULTS: Significant reductions were found in the risk of
      renal transplant rejection in recipients possessing the CCR2-64I (A) allele
      (p=0.03) or 59029-A allele (p=0.03) compared to non-rejector group. There were no
      significant differences in the frequency of CCR5Delta32 polymorphism in rejector
      group compared to non-rejector group (p>0.05). CONCLUSION: It was possible to
      conclude that the chemokine receptors CCR2-V64I (A) and CCR5- 59029 A alleles may
      influence renal allograft survival.

PMID- 19098364
TI  - Null allele frequencies at HLA-G locus in Iranian healthy subjects.
AB  - BACKGROUND: HLA-G gene contains 15 alleles including a null allele, HLA-G*0105N.
      Previous studies have shown that HLA-G*0105N does not encode the complete HLA-G1
      or HLA-G5 isoforms but encodes a functional HLA-G protein with the ability to
      inhibit NK cell cytolysis. Thus, although the biological functions of HLA-G1 and
      HLA-G5 proteins are abrogated, other isoforms such as HLA-G2 can replace their
      roles. Studies on the null allele of HLA-G gene could be useful in understanding
      the genetic variants of HLA-G alleles in ethnic groups. OBJECTIVE: The goal of
      this research was to determine the frequency of HLA-G*0105N null allele in
      Iranian healthy subjects. METHODS: The frequency of HLA-G*0105N null allele was
      evaluated in Iranian healthy subjects by PCR-RFLP method. Genomic DNA was
      isolated from the whole blood of 100 randomly selected, healthy, unrelated
      Iranian individuals using salting-out technique followed by PCR amplification of
      the exon 3 of HLA-G gene. PCR products were digested with PpUM-1 and the resulted
      fragments were analyzed using gel electrophoresis. RESULTS: In this study the
      restriction enzyme digestion confirmed homozygous HLA-G*0105N null allele for 9 %
      of the population. Furthermore obtained results indicated that the total
      frequency of HLA-G*0105N null allele was 20 % in the studied population of Iran.
      CONCLUSION: The final data analysis showed that the total frequency of this
      allele in Iranian people was higher than other ethnic groups that have been
      studied so far.

PMID- 19098365
TI  - The booster phenomenon of tuberculin skin testing in patients receiving
      hemodialysis.
AB  - BACKGROUND: The risk of developing tuberculosis is high among chronic
      hemodialysis patients. The tuberculin skin test (TST) has been in use for
      diagnosing latent TB, but few data are available on TST in hemodialysis patients.
      OBJECTIVE: This study was done to identify the TST reactivity and frequency of
      booster effect in serial TST among hemodialysis patients. METHODS: A total of 100
      patients in three hemodialysis centers were prospectively tested. Patients with
      less than 10mm indurations were given additional TST one and four weeks later to
      determine the frequency of booster effect. RESULTS: The cumulative prevalence of
      a positive TST was 7 % for the first test and 16 % for the third test. There was
      a weak, but significant correlation between TST positivity, serum albumin level,
      urea reduction ratio and KT/V (p<0.05). There was no influence of age, gender,
      hemodialysis duration and primary renal disease. CONCLUSION: This study showed
      that the TST reactivity and booster effect among our hemodialysis patients in
      Iran are lower than in other societies. Inadequate hemodialysis and poor
      nutrition may contribute to the lower tuberculin skin test reactivity in our
      hemodialysis patients.

PMID- 19098366
TI  - Comparison of the salivary immunoglobulin concentration levels between children
      with early childhood caries and caries-free children.
AB  - BACKGROUND: Early Childhood Caries (ECC) is one of the most common chronic
      childhood diseases. In spite of the global decrease in dental caries in the past
      decades, ECC has become a significant problem in many developing countries and
      also in a few industrialized nations. Saliva as a host factor can play an
      important role in the process of dental caries. OBJECTIVE: The aim of this study
      was to compare sIgA and IgG as saliva components between ECC and caries-free
      groups. METHODS: In this cross-sectional study, samples of unstimulated saliva of
      90 children (45 in ECC group & 45 in caries-free group) were taken with Scully
      method. Then the concentration levels of sIgA and IgG were measured with Enzyme
      Linked Immunosorbent Assay and Single Radial Immunodiffusion methods. RESULTS:
      Mean concentration levels of salivary sIgA and IgG were significantly higher
      among children with ECC (p<0.05). There was also a weak inverse correlation
      between sIgA level and DMFT index in ECC group but it was not statistically
      significant (p=0.056). CONCLUSION: The high concentration of salivary
      immunoglobulin in children with ECC may be associated with an increased antigenic
      load, leading to high production of antibodies.

PMID- 19098367
TI  - Cogan's syndrome: a case report.

PMID- 19098368
TI  - A new paradigm in biology - the effect of localization of a protein on its
      antigenicity.

PMID- 19098369
TI  - The role of transient receptor potential channels in metabolic syndrome.
AB  - Metabolic syndrome is correlated with increased cardiovascular risk and
      characterized by several factors, including visceral obesity, hypertension,
      insulin resistance, and dyslipidemia. Several members of a large family of
      nonselective cation entry channels, e.g., transient receptor potential (TRP)
      canonical (TRPC), vanilloid (TRPV), and melastatin (TRPM) channels, have been
      associated with the development of cardiovascular diseases. Thus, disruption of
      TRP channel expression or function may account for the observed increased
      cardiovascular risk in metabolic syndrome patients. TRPV1 regulates adipogenesis
      and inflammation in adipose tissues, whereas TRPC3, TRPC5, TRPC6, TRPV1, and
      TRPM7 are involved in vasoconstriction and regulation of blood pressure. Other
      members of the TRP family are involved in regulation of insulin secretion, lipid
      composition, and atherosclerosis. Although there is no evidence that a single TRP
      channelopathy may be the cause of all metabolic syndrome characteristics, further
      studies will help to clarify the role of specific TRP channels involved in the
      metabolic syndrome. (Hypertens Res 2008; 31: 1989-1995).

PMID- 19098370
TI  - Transcatheter closure of adult patent ductus arteriosus with severe pulmonary
      hypertension.
AB  - The purpose of this study was to investigate the application of trial balloon
      occlusion for permanent closure of patent ductus arteriosus (PDA) with severe
      pulmonary hypertension (PH) in adults, and to assess its immediate and short-term
      results. From September 1999 to September 2005, a total of ten adults (two males,
      ages ranging from 20 to 54 years) with PDA who met the criterion for severe PH
      (basal pulmonary vascular resistance >8 Wood units) received trial balloon
      occlusion via an embolectomy balloon catheter. Post-occlusion hemodynamics, along
      with an overall clinical and hemodynamic assessment, was used to consider the
      indication of closure of PDA. Nine of the patients underwent successful
      transcatheter closure of PDA and subsequently used Amplatzer occluder devices.
      Chest X-ray, cardiography and echocardiography were used for follow-up evaluation
      of the treatment within 6 months after successful closure of PDA. No patient had
      a detectable residual shunt by color flow mapping or any other complications
      (device migration, hemolysis, endocarditis, etc.) at follow-up. In conclusion,
      trial balloon occlusion helps to determine anticipated hemodynamics after closure
      of PDA, so it is conducive to indicating permanent closure of adult PDA with
      reversible but severe PH. Furthermore, satisfactory immediate and short-term
      outcomes have proven this method to be safe and valid. (Hypertens Res 2008; 31:
      1997-2002).

PMID- 19098371
TI  - Prolonged QT interval and reduced heart rate variability in patients with
      uncomplicated essential hypertension.
AB  - A prolonged QT interval is a risk factor for ischemic heart disease in
      hypertensive subjects. Heart rate variability (HRV) is both an index of autonomic
      function and an important prognostic factor in several diseases. The aim of the
      present study was to evaluate the relation between a prolonged QT interval and
      autonomic nervous system function in patients with untreated uncomplicated
      essential hypertension. Two hundred and fifteen untreated patients with essential
      hypertension underwent a Holter ECG equipped with software dedicated to HRV and
      QT analyses. Nine percent of the patients showed a corrected QT (QTc) >or=440 ms.
      The HRV indexes in the time domain (SDNN, SDNN index, RMSSD, and pNN50) were
      significantly reduced in the patients with a prolonged QTc compared to those with
      a normal QTc (SDNN 24 h: 126.4+/-29.9 vs. 143.9+/-35.4 ms, p=0.02; SDNN index
      [nighttime]: 85.9+/-32.4 vs. 115.5+/-36.7 ms, p=0.0006; RMSSD 24 h: 22.2+/-7.7
      vs. 31.2+/-13.0 ms, p=0.0007; pNN50 24 h: 4.4+/-4.9 vs. 9.7+/-8.4%, p=0.0006).
      The linear correlation analysis between QTc length and HRV parameters showed a
      significant negative correlation with all the time-domain indexes. Such a
      correlation was maintained for RMSSD 24 h, pNN50 24 h and SDNN index (nighttime)
      after correction for gender and age. The present study shows that, even prior to
      the development of cardiac hypertensive disease, a prolongation of the QTc and a
      reduced HRV, both markers of cardiovascular risk, coexist in a proportion of
      patients with untreated essential hypertension. Further studies are warranted to
      evaluate whether the combination of such markers can identify hypertensive
      patients at risk for life-threatening arrhythmias and sudden death. (Hypertens
      Res 2008; 31: 2003-2010).

PMID- 19098372
TI  - OMEGA study: design, baseline data, metabolic syndrome prevalence in a large
      scale observational study of hypertensive patients: The Olmesartan Mega Study to
      Determine the Relationship between Cardiovascular Endpoints and Blood Pressure
      Goal Achievement study.
AB  - Elevated systolic blood pressure increases the risk of cardiovascular events, as
      shown by a number of meta-analyses of large-scale clinical trials. As concerns
      the prognostic impact of the metabolic syndrome on cardiovascular events, few
      large-scale studies are available in the Japanese hypertensive population. The
      prospective, large-scale, observational OMEGA (Olmesartan Mega Study to Determine
      the Relationship between Cardiovascular Endpoints and Blood Pressure Goal
      Achievement) study sought to examine the relationship between the incidence of
      cardiovascular disease (CVD) and achieved blood pressure, metabolic syndrome,
      lifestyle factors and other risk factors for CVD in patients with hypertension.
      Of the 15,313 enrolled patients from 2,219 institutions in Japan, we report here
      the baseline characteristics of the 14,841 eligible patients whose baseline data
      were collected as of October 31, 2007. Men and women 50 to 79 years old (mean age
      65) with physician-diagnosed hypertension were enrolled, and all patients were
      treated with open-label olmesartan medoxomil (5 to 40 mg daily). The majority of
      patients (75%) had mild to moderate hypertension. The prevalences of dyslipidemia
      and diabetes mellitus were 48% and 24%, respectively. The metabolic syndrome was
      identified in 48% and 19% of the evaluable men and women, respectively, using the
      criteria of the Japanese Society of Internal Medicine. Men with the metabolic
      syndrome were at the greatest risk for CVD, and a greater proportion of men than
      of women had all five metabolic syndrome components. The complete follow-up data
      from the OMEGA study will provide much-needed information to guide treatment in
      patients with hypertension and the metabolic syndrome. (Hypertens Res 2008; 31:
      2011-2017).

PMID- 19098373
TI  - The relationships of cardiovascular disease risk factors to flow-mediated
      dilatation in Japanese subjects free of cardiovascular disease.
AB  - We examined the relationship of several cardiovascular disease (CVD) risk factors
      to flow-mediated vasodilatation of the brachial artery (FMD) and the clustering
      effect of risk factors on FMD in Japanese subjects free of CVD. In 819 Japanese
      subjects free of CVD (age 45+/-10 years, 611 men and 208 women), FMD correlated
      significantly with the Framingham risk points score (FRS) (r=-0.27, p<0.01). FMD
      was higher in subjects in the 1st tertile of the FRS range than in patients in
      either the 2nd or 3rd tertiles of the FRS range, but it was similar between the
      subjects in the 2nd and 3rd tertiles. FMD was found to have a significant
      independent negative correlation with age (beta=-0.19, p<0.01), gender (beta=
      0.024, p<0.01) and smoking habit (beta=-0.08, p=0.02). In subjects >or=50 years
      of age, the FMD in men with one CVD risk factor, excluding smoking, was similar
      to that in men with no CVD risk factors. CVD risk factors did not attenuate FMD
      in women. Thus, in Japanese subjects free of CVD, FMD may be a useful marker of
      CVD risk, but it may not be a robust marker for endothelial damage related to
      clusters of CVD risk factors. Age, gender and smoking were independent variables
      related to the impairment of FMD, which therefore appears to be less applicable
      in subjects aged 50 or more, and especially in women. (Hypertens Res 2008; 31:
      2019-2025).

PMID- 19098374
TI  - Impact of metabolic syndrome components on the incidence of cardiovascular
      disease in a general urban Japanese population: the suita study.
AB  - Abdominal obesity is a prerequisite for some definitions of metabolic syndrome
      (MetS). We investigated the impact of MetS defined by two different criteria,
      which either did or did not require abdominal obesity as a prerequisite, on
      cardiovascular disease (CVD) incidence in an urban Japanese cohort study. We
      studied 5,332 Japanese (aged 30-79 years, without CVD at baseline), who completed
      a baseline survey (September 1989 to March 1994) and were followed up through
      December 2005. MetS was defined by the NCEP-ATPIII (modified by Asian obesity
      criteria) and the Japanese criteria. After 61,846 person-years of follow-up, we
      documented 317 CVD incidences. The MetS frequencies of the Japanese and of the
      modified NCEP-ATPIII criteria were 17.7% and 25.1% for men and 5.0% and 14.3% for
      women, respectively. The multivariate hazard ratios (HRs; 95% confidence
      intervals [CI]) of CVD incidence for MetS by the modified NCEP-ATPIII criteria
      were 1.75 (1.27-2.41) in men and 1.90 (1.31-2.77) in women, and those for MetS by
      the Japanese criteria were 1.34 (0.96-1.87) in men and 2.20 (1.31-3.68) in women.
      The multivariate HRs of CVD incidence for MetS for the Japanese and for the
      modified NCEP-ATPIII criteria were 2.92 (1.54-5.55) and 1.94 (0.98-3.82) in men
      under 60 years old, respectively. The CVD incidence risks increased according to
      the number of MetS components. The risks were similar among participants with the
      same number of MetS components, regardless of abdominal obesity. In conclusion,
      the number of MetS components (modified NCEP-ATPIII criteria) may be more
      strongly associated with CVD incidence than the abdominal obesity essential
      criteria (the Japanese criteria) in a general urban Japanese population.
      (Hypertens Res 2008; 31: 2027-2035).

PMID- 19098375
TI  - Patients' self-reported adherence to cardiovascular medication using electronic
      monitors as comparators.
AB  - The aim of this study was to evaluate self-reporting of adherence to
      cardiovascular medication using electronic pillboxes (medical event monitoring
      system [MEMS]) as the gold standard comparator. In total, 78 individuals (52%
      hypertensives, 21% diabetics, 27% with dyslipidemia) were recruited prospectively
      from an outpatient clinic setting in Switzerland. Participants completed two self
      report measures (visual analogue scale [VAS] and a validated self-reporting
      questionnaire) at baseline and were asked to use MEMS as their pillbox for the
      subsequent 10 weeks. Patients expressed their medication adherence behaviour on a
      VAS (0 mm="I never take any tablets"; 100 mm="I take all tablets as prescribed")
      and entered one of six numbers (from 1: perfect adherence to 6: non-adherence) on
      the questionnaire. Medication compliance was monitored for 75 d on average. Mean
      (+/-SD, range) scores for MEMS with respect to timing adherence, correct dosing,
      and self-administration adherence were 79+/-25% (8-100%), 83+/-20% (24-100%), and
      92+/-17% (54-118%), respectively. A majority of participants (78.8%) over
      reported their adherence to the VAS (93+/-7 mm, 73-100), and VAS scores
      correlated poorly with MEMS recordings (Spearman's rho for timing adherence,
      correct dosing, self-administration adherence 0.29 [p=0.018], 0.24 [p=0.051],
      0.26 [p=0.036], respectively). Similarly, we found no correlation between
      adherence as expressed in the questionnaire and MEMS (regression coefficients
      <0.1). We conclude that a majority of patients over-report adherence to
      cardiovascular medication if asked to complete a visual analogue scale and a
      validated questionnaire. Therefore, using self-reporting as the sole means of
      assessing medication compliance is insufficiently accurate to detect poor
      adherence. (Hypertens Res 2008; 31: 2037-2043).

PMID- 19098376
TI  - Plasma tissue inhibitor of matrix metalloproteinase-1 level is increased in
      normotensive non-dippers in association with impaired glucose metabolism.
AB  - Non-dipping (nocturnal blood pressure [BP] decrease<10%) is related to
      accelerated urinary salt excretion (u-NaCl), and increased risk of left
      ventricular hypertrophy (LVH) and cardiovascular events. We evaluated whether non
      dippers exhibit an advanced extracellular matrix fibrosis, in relation to
      increased u-NaCl, among normotensive subjects. We measured plasma tissue
      inhibitor of matrix metalloproteinase-1 (TIMP-1), a marker of collagen fibrosis
      in extracellular matrix, to evaluate the relationship between non-dipping and u
      NaCl in 73 normotensive subjects (no antihypertensive medications, clinic
      BP<140/90 mmHg and/or 24-h ambulatory BP<125/80 mmHg). Non-dippers had a
      significantly higher percentage of subjects with impaired fasting glucose (IFG)
      or diabetes mellitus (DM), and had a greater left ventricular mass index (LVMI),
      plasma TIMP-1 level and u-NaCl than dippers (IFG or DM: 24.0 vs. 6.3%, p=0.029;
      LVMI: 118+/-31 vs. 103+/-26 g/m(2), p=0.039; TIMP-1: 168+/-35 vs. 151+/-30 pg/mL,
      p=0.035; u-NaCl: 5.1+/-1.7 vs. 3.9+/-1.7 g/12 h, p=0.005). In logistic regression
      analysis, non-dipping was independently associated with u-NaCl and TIMP-1. u-NaCl
      was correlated with non-dipping (r=0.35, p=0.003) and serum glucose level
      (r=0.26, p=0.027). On the other hand, TIMP-1 level was significantly correlated
      with the presence of IFG or DM (r=0.23, p=0.046), but not with u-NaCl. In
      conclusion, plasma TIMP-1 level, a measure of cardiovascular fibrosis in
      extracellular matrix, is greater in normotensive non-dippers than in dippers;
      however, the increased TIMP-1 level may be related to impaired glucose
      metabolism, and non-dipping may be related to increased u-NaCl associated with
      high serum glucose levels in normotensive subjects. (Hypertens Res 2008; 31: 2045
      2051).

PMID- 19098377
TI  - Chronic kidney disease increases cardiovascular mortality in 80-year-old subjects
      in Japan.
AB  - Chronic kidney disease (CKD) is one of the greatest risk factors for
      cardiovascular disease (CVD). The contribution of CKD to CVD mortality is not
      well understood in very elderly patients. Our study examined whether CKD might be
      a risk factor for total and CVD mortality in very elderly Japanese individuals. A
      total of 621 participants were enrolled, all of whom were 80 years old. The
      subjects were divided on the basis of the presence (CKD(+) group, n=280) or
      absence (CKD(-) group, n=341) of CKD. CKD was defined by as an estimated
      glomerular filtration rate (eGFR) below 60 mL/min/1.73 m(2). The eGFR of the
      CKD(+) and CKD(-) groups was 49.7+/-8.5 and 70.9+/-9.5 mL/min/1.73 m(2),
      respectively. During the 4-year study period, 87 individuals died, and 25 of
      those deaths were due to CVD. A Cox multivariate regression analysis revealed no
      association between total mortality and CKD (relative risk [RR] 1.17, confidence
      interval [CI] 0.75-1.82, p=0.50). However, the CVD mortality was significantly
      increased in the CKD(+) group (RR 4.60, CI 1.69-12.52, p=0.003). CKD
      significantly increased the CVD mortality in subjects who were not taking
      antihypertensive medication (RR 5.15, CI 1.04-25.50, p=0.04). Our results suggest
      that CKD increases the risk of CVD mortality in very elderly individuals. It is
      not only important to prevent progression toward CKD in patients who do not
      suffer from CKD, but also critical to manage the risk factors for CVD in patients
      with CKD, despite their advanced age. (Hypertens Res 2008; 31: 2053-2058).

PMID- 19098378
TI  - Postural changes may influence popliteal atherosclerosis by modifying local
      circumferential wall tension.
AB  - Atherosclerosis of peripheral arteries typically affects vessels of the lower
      limbs, suggesting that local hemodynamic stimuli play a role in this process. Our
      study evaluated the effects of body postural changes on carotid and popliteal
      blood pressure, circumferential wall tension (CWT) and arterial strain, and
      investigated the relationship between such hemodynamic parameters and intima
      media thickness (IMT) of these arteries. One hundred seventeen nondiabetic,
      nonhypertensive, nonsmoker subjects (48 men and 69 women) were enrolled and had
      their blood pressure measured in the arm and calf in supine and orthostatic
      positions. Echo-doppler analysis evaluated the common carotid and popliteal
      arteries after blood pressure measurements, while CWT was calculated according to
      Laplace's law. The results showed that changing from supine to orthostatic
      posture increased blood pressure and CWT in popliteal but not in carotid
      arteries. Partial correlation analysis adjusted for age and body mass index
      revealed no major relationship between IMT of the studied vessels and local blood
      pressure or arterial strain. Conversely, supine and orthostatic CWT exhibited
      comparable correlation coefficients with carotid IMT, while orthostatic CWT
      displayed a stronger relationship with popliteal IMT than with supine CWT. These
      results were confirmed by multiple linear regression analysis that included age,
      sex, body mass index, lipid fractions and glucose as independent variables.
      Overall, our results indicate that orthostatic CWT is a stronger hemodynamic
      predictor of popliteal IMT than supine CWT, suggesting that erectile posture may
      be a potential risk factor for popliteal atherosclerosis because it increases the
      local hemodynamic burden. (Hypertens Res 2008; 31: 2059-2064).

PMID- 19098379
TI  - Diurnal blood pressure abnormalities are related to endothelial dysfunction in
      patients with non-complicated type 1 diabetes.
AB  - Patients with diabetes have an increased cardiovascular morbidity and mortality
      despite interventions to prevent these outcomes. Abnormalities in diurnal blood
      pressure patterns are also associated with excess cardiovascular mortality. The
      aim of this study was to determine the effects of diurnal blood pressure patterns
      on endothelial function and oxidative stress in patients with uncomplicated type
      1 diabetes mellitus. Thirty-two normotensive and normoalbuminuric type 1 diabetic
      patients (21 dipper and 11 nondipper) and 37 healthy (27 dipper and 10 nondipper)
      volunteers underwent 24-h ambulatory blood pressure monitoring. Their endothelial
      functions were evaluated using flow mediated dilatation (FMD) and by measuring
      nitric oxide and thiobarbituric acid reactive substances (TBARS). Dippers were
      defined as subjects who exhibited an average reduction in both systolic and
      diastolic blood pressure of greater than 10% between day and night periods.
      Nondipper type 1 diabetic patients and controls had nighttime systolic and
      diastolic blood pressure values that were significantly higher than those of
      dipper diabetic patients (p<0.05) and dipper controls (p<0.01). Values of FMD for
      nondipper diabetic patients (5.12+/-2.2%) were significantly lower than those in
      dipper diabetic patients (10.19+/-2.5%, p<0.01), nondipper (10.08+/-2.9%,
      p<0.001) and dipper controls (11.76+/-3.8%, p<0.001). Additionally, levels of
      TBARS in the dipper diabetic group and dipper controls were significantly lower
      than those in the nondipper diabetic group (p<0.05). In conclusion, only type 1
      diabetic patients with a nondipping pattern of blood pressure exhibited changes
      that may lead to endothelial dysfunction and atherosclerosis. (Hypertens Res
      2008; 31: 2065-2073).

PMID- 19098380
TI  - High salt intake enhances blood pressure increase during development of
      hypertension via oxidative stress in rostral ventrolateral medulla of
      spontaneously hypertensive rats.
AB  - High salt intake increases blood pressure (BP) in spontaneously hypertensive rats
      (SHR), and central neural mechanisms are suggested to be involved. Increased
      generation of reactive oxygen species (ROS) in the rostral ventrolateral medulla
      (RVLM) contributes to the neural mechanism of hypertension in SHR. We sought to
      examine whether high salt intake increases hypertension in SHR and whether the
      increased ROS in the RVLM contributes to this mechanism. Male SHR and Wistar
      Kyoto rats (WKY) (6 weeks old) were fed a high-salt diet (8%: HS-S; HS-W) or a
      regular-salt diet (0.5%: RS-S; RS-W) for 6 weeks. Systolic BP was significantly
      higher in HS-S than in RS-S at 12 weeks of age (244+/-5 vs. 187+/-7 mmHg, n=8;
      p<0.05). Urinary norepinephrine excretion was significantly higher in HS-S than
      in RS-S. Thiobarbituric acid-reactive substances levels in the RVLM were
      significantly higher in HS-S than in RS-S (9.9+/-0.5 vs. 8.1+/-0.6 mumol/g wet
      wt, n=5; p<0.05). Microinjection of tempol or valsartan into the RVLM induced
      significantly greater BP reduction in HS-S than in RS-S. The increase in
      angiotensin II type 1 receptor (AT(1)R) expression and the increase in reduced
      nicotinamide-adenine dinucleotide phosphate (NAD(P)H) oxidase activity in the
      RVLM were significantly greater in HS-S than in RS-S. These findings indicate
      that high salt intake exacerbates BP elevation and sympathetic nervous system
      activity during the development of hypertension in SHR. These responses are
      mediated by increased ROS generation that is probably due to upregulation of
      AT(1)R/NAD(P)H oxidase in the RVLM. (Hypertens Res 2008; 31: 2075-2083).

PMID- 19098381
TI  - Stimulatory effects of low-dose 3-hydroxy-3-methylglutaryl coenzyme a reductase
      inhibitor fluvastatin on hepatocyte growth factor-induced angiogenesis:
      involvement of p38 mitogen-activated protein kinase.
AB  - Therapeutic angiogenesis has received much attention for its potential benefits
      in ischemic vascular disorders. Recently, the clinical application of hepatocyte
      growth factor (HGF) for therapeutic angiogenesis has become well known. Statins
      have also been reported to promote angiogenesis and ameliorate ischemic
      conditions. In the present study, we examined the effects of fluvastatin on HGF
      induced angiogenesis using a human umbilical vein endothelial cell (HUVEC)/normal
      human dermal fibroblast (NHDF) co-culture system. The HGF-induced angiogenesis
      was augmented by fluvastatin at low dose, but it was decreased at high dose.
      Although fluvastatin increased vascular endothelial growth factor expression in
      NHDFs, it was observed only at a high dose. Low-dose fluvastatin decreased the
      HGF-induced p38 mitogen-activated protein kinase (MAPK) phosphorylation (Thr
      180/Tyr-182) and HUVEC apoptosis in the presence of HGF. SB203580, a p38 MAPK
      inhibitor, ameliorated anisomycin (a p38 MAPK activator)-induced angiogenesis
      suppression in the presence of HGF. Moreover, the augmentation of the HGF-induced
      angiogenesis by fluvastatin was abrogated by the p38 MAPK inhibitors, SB203580,
      SB202190, and FR167653. High-dose fluvastatin decreased Akt phosphorylation (Ser
      473) and HUVEC proliferation, and it increased p27(kip1) in HUVECs.
      Interestingly, fluvastatin decreased the mRNA expression of integrins and tissue
      inhibitor of metalloproteinases (TIMPs) in HUVECs. Our data therefore indicate
      that the stimulatory effects of low-dose fluvastatin on the HGF-induced
      angiogenesis are mediated by its inhibitory effects on p38 MAPK phosphorylation
      induced by HGF, which may result in the suppression of EC apoptosis. High-dose
      fluvastatin inhibits Akt phosphorylation and HUVEC proliferation, and it
      increases p27(kip1), which may result in its inhibitory effects on angiogenesis.
      In addition, integrins and TIMPs are candidates for angiogenesis regulation by
      fluvastatin. (Hypertens Res 2008; 31: 2085-2096).

PMID- 19098382
TI  - Metabolic syndrome is a poor predictor of outcome after coronary interventions in
      high-risk patients.

PMID- 19098384
TI  - Aortic aging in the Fischer 344 / NNiaHSd x Brown Norway / BiNia Rat.
AB  - Aging is now recognized as one of major risk factors for cardiovascular disease
      (CVD). It is well documented that elderly populations show increased incidence of
      CVD symptomology but whether these changes are directly related to aging is not
      well understood since the possibility exists that other age-associated
      pathologies in different organ systems could impact on cardiovascular function.
      Hence, the development of an aging model with reduced systemic illness could
      invigorate efforts to understand the direct role of aging in CVD progression. The
      Fischer 344 / NNIaHSD x Brown Norway / BiNia rat (F344BN) has been proposed as a
      potential model for aging that exhibits reduced systemic pathology and increased
      longevity compared to other models. Here we examine the current literature
      regarding the F344BN, focusing on age-associated changes in aortic structure and
      function.

PMID- 19098385
TI  - Basic and translational research on proteinase-activated receptors: preface.

PMID- 19098386
TI  - Basic and translational research on proteinase-activated receptors: regulation of
      nicotine reward by the tissue plasminogen activator (tPA) - plasmin system via
      proteinase-activated receptor 1.
AB  - Nicotine, a primary component of tobacco, is one of the most abused drugs
      worldwide. Mesolimbic dopaminergic neurons mediate the rewarding effects of
      abused drugs, including nicotine. We show that the tissue plasminogen activator
      (tPA) - plasmin system regulates nicotine-induced reward and dopamine release in
      the nucleus accumbens (NAc) by activating proteinase-activated receptor 1
      (PAR(1)). Nicotine-induced conditioned place preference and dopamine release in
      the NAc are diminished in tPA knockout (tPA-/-) mice. The defect of nicotine
      induced dopamine release in tPA-/- mice is reversed by microinjection of either
      exogenous tPA or plasmin into the NAc. Acute nicotine treatment increases tPA
      protein levels and promoted the release of tPA into the extracellular space. The
      expression of PAR(1) on dopaminergic neurons is evident and the activation of
      PAR(1) by plasmin is demonstrated by assaying GTP-gammaS binding. Finally,
      nicotine-induced conditioned place preference and dopamine release are diminished
      in PAR(1)-/- mice. These findings suggest that targeting the tPA-plasmin-PAR(1)
      system would provide new therapeutic approaches for the treatment of nicotine
      dependence.

PMID- 19098387
TI  - Basic and translational research on proteinase-activated receptors: implication
      of proteinase/proteinase-activated receptor in gastrointestinal inflammation.
AB  - Recently, the role of serine proteinases in the pathogenesis of inflammation and
      autoimmune diseases via interaction with the proteinase-activated receptor (PAR)
      has attracted attention. Activation of PAR has a pro-inflammatory effect through
      the overproduction of inflammatory cytokines such as interleukin (IL)-6 and IL-8.
      PAR(2) activation in human esophageal epithelial cells by trypsin induces
      NFkappaB- and AP-1-dependent IL-8 production in association with activation of
      p38 MAPK and ERK1/2, suggesting that esophageal inflammation may be induced by
      PAR(2) activation via reflux of trypsin. It has been also proposed that
      Helicobacter pylori (H. pylori) induces PAR expression in the gastric epithelial
      cells and H. pylori-derived serine proteinase promotes IL-8 production via PAR in
      the epithelial cells. In addition, an increase of PAR-dependent IL-8 production
      has been observed in H. pylori-infected human gastric mucosa, suggesting an
      important role for PAR(2) in the modulation of gastric inflammation associated
      with H. pylori. Recent studies have strongly indicated that tryptase and PAR are
      implicated in the pathogenesis of inflammatory bowel disease and experimental
      colitis. We demonstrated that anti-tryptase therapy may become a new therapeutic
      strategy in human ulcerative colitis. Thus, the role of PAR in the
      gastrointestinal tract has been gradually clarified, but further investigations
      are needed because the receptor has a variety of functions.

PMID- 19098388
TI  - Basic and translational research on proteinase-activated receptors: proteinase
      activated receptors in female reproductive tissues and endometriosis.
AB  - During the menstrual cycle, dynamic morphological changes are observed in the
      ovarian follicle and the endometrium. These changes are associated with the onset
      of the inflammatory response in which many proteinases play various roles.
      Thrombin-induced activation of PAR(1) (proteinase-activated receptor 1)
      stimulates the production of interleukin-8 (IL-8) and monocyte chemoattractant
      protein-1 (MCP-1) in human granulosa cells, suggesting a possible role for PAR(1)
      in the ovulatory process. In the endometrium, PAR(2) expression increases during
      the menstrual period. PAR(2) activation induces IL-8 production and cell
      proliferation in human endometrial stromal cells. PAR(1) also stimulates
      proinflammatory cytokine production in human endometrial stromal cells. Thus, the
      PARs may be important in directing the dynamic changes of the endometrium. PARs
      also appear to play a role in endometriosis, a common gynecological disease,
      since activation of PAR(1) and PAR(2) induces the secretion of inflammatory
      cytokines and the proliferation of stromal cells in endometriotic lesions. Taken
      together, PARs appear to play diverse roles in the human reproductive organs.

PMID- 19098389
TI  - Basic and translational research on proteinase-activated receptors: the role of
      thrombin receptor in cerebral vasospasm in subarachnoid hemorrhage.
AB  - Cerebral vasospasm is one of the major complications of subarachnoid hemorrhage
      (SAH). The prevention and treatment of cerebral vasospasm thus plays a critical
      role in the management of SAH patients. However, the mechanism of cerebral
      vasospasm still remains elusive, while effective therapeutic strategies also
      remain to be established. The role of thrombin and its receptor proteinase
      activated receptor 1 (PAR(1)) in cerebral vasospasm was investigated using a
      rabbit double hemorrhage SAH model. The expression of PAR(1) was up-regulated and
      the contractile response to thrombin was markedly enhanced in the basilar artery
      of SAH models. The intrathecal administration of a PAR(1) antagonist prevented
      the up-regulation of PAR(1) and the enhancement of the contractile responses to
      thrombin in SAH. These observations thus suggest that PAR(1) may play a pivotal
      role in post-hemorrhagic cerebral vasospasm in SAH. Following SAH, thrombin
      activates PAR(1), thereby up-regulating the expression of PAR(1), which
      culminates in the increased contractile response to thrombin in the basilar
      artery. PAR(1) antagonists are thus anticipated to be a novel therapeutic
      strategy for cerebral vasospasm. However, further studies are needed before
      establishing the clinical usefulness of PAR(1) antagonists.

PMID- 19098390
TI  - Basic and translational research on proteinase-activated receptors: antagonism of
      the proteinase-activated receptor 1 for thrombin, a novel approach to
      antiplatelet therapy for atherothrombotic disease.
AB  - Atherothrombotic disease is a leading public health problem. Although current
      antiplatelet agents, such as aspirin and adenosine diphosphate (ADP)-receptor
      antagonists, reduce the morbidity and mortality associated with atherothrombotic
      disease, the residual risk for ischemic events remains substantial. The high
      residual risk despite dual antiplatelet therapy can be attributed to the fact
      that platelets possess multiple pathways of activation that are not all inhibited
      by aspirin and ADP-receptor antagonists. Among these, binding of thrombin to the
      proteinase-activated receptor 1 (PAR(1)) is the most potent platelet activation
      pathway. In addition, the PAR(1) pathway does not appear to be essential for
      initiating hemostasis. Inhibition of the PAR(1) receptor thus offers a possible
      new therapeutic approach with a potentially improved benefit-to-risk profile for
      treatment of patients with atherothrombotic disease. Preclinical and clinical
      studies have confirmed that SCH 530348, a potent, orally active thrombin-receptor
      antagonist selective for PAR(1), does not increase bleeding liability when added
      to dual antiplatelet therapy. Currently, two large ongoing phase 3 clinical
      trials are evaluating the efficacy and safety of SCH 530348 in combination with
      the standard of care in patients with acute coronary syndromes as well as for
      secondary prevention in patients with previous history of atherothrombotic
      disease.

PMID- 19098392
TI  - Efficacy of oral treatment with tacrolimus in the renal transplant model in
      cynomolgus monkeys.
AB  - Many studies have examined the efficacy of tacrolimus in rats and dogs, but few
      have reported its evaluation in cynomolgus monkeys. The aim of this study was to
      clarify the efficacy of tacrolimus in a cynomolgus monkey renal transplant model
      based on the efficacy of various doses. Monkeys that had undergone renal
      transplant were treated with a vehicle or 0.5, 1.0, or 2.0 mg/kg of tacrolimus by
      oral administration. Tacrolimus administration prolonged animal survival in a
      dose-dependent manner, and the median survival time (MST) was 11, 21, and >90
      days for the 0.5, 1.0, and 2.0 mg/kg tacrolimus groups, respectively. The MST of
      the vehicle group was 6 days. Histopathological analyses of all transplanted
      kidneys were also performed. Typical pathological findings of acute rejection
      were observed in both the vehicle and tacrolimus (0.5 and 1.0 mg/kg)-treated
      groups. Only limited mononuclear cell infiltration and hemorrhage were present in
      the tacrolimus (2.0 mg/kg)-treated group. In conclusion, 2.0 mg/kg was considered
      to be a therapeutic dose in this model, and 0.5 or 1.0 mg/kg could be used for a
      study when efficacy of a new compound is evaluated in a combination therapy with
      tacrolimus.

PMID- 19098391
TI  - Inhibitory effects of isoliquiritigenin and licorice extract on voltage-dependent
      K(+) currents in H9c2 cells.
AB  - The effect of isoliquiritigenin (ISL), a component of licorice, on the voltage
      dependent, ultra-rapidly activating delayed-rectifier K(+) current (IKur) was
      examined in H9c2 cells, a cell-line derived from rat cardiac myoblasts. IKur was
      recorded using the whole-cell patch clamp method with a pipette solution
      containing 140 mM K(+). Depolarizing voltage pulses of 200-ms duration were given
      with 10-mV steps every 10 s from -40 mV holding potential. ISL inhibited IKur in
      a concentration-dependent manner. The median inhibitory concentration (IC(50)) of
      ISL was approximately 0.11 microM and the Hill coefficient was 0.71. Using CHO
      cells expressing Kv1.5 IKur channels, ISL also inhibited Kv1.5 IKur, but less
      potently than the IKur current in H9c2 cells. Furthermore, in H9c2 cells, the
      licorice extract itself inhibited IKur in a manner similar to ISL. We conclude
      that ISL, one component of licorice, is a potent inhibitor of K(+) channels,
      which specifically in H9c2 cells could be Kv2.1, and that this inhibition may be
      involved in various pharmacological effects of licorice.

PMID- 19098393
TI  - [Front-line drug discovery system for cancer].
AB  - Research and development of anticancer drugs targeting causative molecules of
      tumorigenesis have been actively promoted since discovery of human oncogenes in
      the 1980s. Innovative molecular-targeted drugs such as Trastuzumab and Imatinib
      are typical fruits of the efforts over the past decade. In the anticancer drug
      market at present, a family of these molecular-targeted drugs has come to
      outperform conventional chemotherapeutic agents such as DNA acting agents,
      tubulin binders, and antimetabolites. Methodology developments and achievements
      of genomics research including completion of the human genome sequencing in 2003
      are drastically changing the drug discovery system for cancer. Cancer medicine
      now enters an era of personalized medicine in which characteristics of a cancer
      and the individual constitution of a patient are reflected in the therapeutic
      treatment. Utilization of biomarkers is an important issue for this personalized
      medicine. It is strongly pointed out that the action of a drug on its target
      should be validated at the early phase of clinical trials in view of the proof of
      concept(POC) in order to increase the success rate of drug discovery. In this
      article, the current state and the future of dramatically-evolving anticancer
      drug discovery are reviewed.

PMID- 19098394
TI  - [Diagnosis and treatment for brain and spinal metastases].
AB  - Brain and spinal metastases are common complications of cancer and have the major
      impact on the prognosis of those patients. Survival time of such patients is
      still less than one year. Surgery with whole-brain radiation therapy (WBRT)has
      been used in the treatment of single-brain metastasis with a diameter of more
      than 3 cm. Stereotactic radiosurgery(SRS)including gamma knife is widely used for
      treatment for small and multiple brain metastases, however, recent clinical
      studies revealed that SRS+WBRT is superior to WBRT or SRS alone in survival time
      and local tumor control rates. Radiotherapy(RT)has also been a standard therapy
      for metastatic spinal cord compression and intramedullary metastasis, but recent
      studies revealed the effectiveness of surgery+RT for spinal metastasis. To
      improve QOL and survival of patients with brain and spinal metastasis, optimum
      and immediate management based on evidence- based medicine(EBM)is necessary.

PMID- 19098395
TI  - [Treatment for oncogenic emergencies of the cardiovascular system].
AB  - Cardiac tamponade and superior vena cava(SVC)syndrome are important oncogenic
      emergencies of the cardiovascular system. Depending on the nature of the
      emergency, its severity, the progression of malignancies, general condition and
      proper treatment should be chosen in each patient. The treatment to be first
      considered for cardiac tamponade is percardiocentesis and tube pericardiotomy. It
      is important to improve cardiac function by prompt drainage after diagnosis with
      cardiac ultrasonography. To avoid recurrence of cardiac tamponade, pericardial
      fenestration and instillation of anticancer agents into the pericardium are
      sometimes added. In patients with SVC syndrome, treatment should be determined
      after enhanced computed tomography. Although surgery, chemotherapy and radiation
      are important treatments for malignances, stenting in obstruction of SVC is a
      safe and effective method to improve symptoms promptly.

PMID- 19098396
TI  - [Respiratory system].
AB  - Patients with malignancies are subject to developing a set of complications that
      require emergency evaluation and treatment. Emergencies in the cancer patients
      are particularly complex. Since the severity of emergency situations varies
      individually, the appropriate treatment should be determined based on the
      clinical condition of individual patients. Patients with potentially curable
      disease should be managed aggressively with full intervention to treat the
      emergency situation, whereas this may not be appropriate for patients entering
      the terminal phase of their life intervention. An oncogenic emergency involving
      respiratory malignant disease is rare, but special medical knowledge and skills
      are required. Therefore, we should train for that situation in a medical
      examination. In this review, we suggest the diagnosis and initial therapy for
      common emergencies involving respiratory malignant disease, such as severe airway
      obstruction, massive hemoptysis, pneumothorax, and hemoneumothorax.

PMID- 19098397
TI  - [Oncologic emergency in the abdomen].
AB  - In general, cancer does not progress very rapidly, however, it sometimes causes
      an oncologic emergency that requires immediate treatment, depending on the
      location and progression of the disease. Hemorrhage, obstruction, and perforation
      are typical abdominal oncologic emergencies. As for gastrointestinal bleeding,
      endoscopic hemostasis is a common treatment of choice. Transcatheter arterial
      embolization is the first treatment to select in case of intra-abdominal
      hemorrhage caused by rupture of a hepatocellular carcinoma. Patients with upper
      gastrointestinal obstruction for unresectable cancer need to be treated
      considering their prognoses and treatment effects. Those with colorectal
      obstructions with cancers first need decompression. Patients with colorectal
      perforation should be operated immediately to prevent septic shock. Acute
      obstructive suppurative cholangitis needs endoscopic retrograde cholangiography
      for immediate diagnosis and treatment. Abdominal oncologic emergencies have
      decreased due to recent diagnostic and therapeutic improvements. However, it
      remains a crucial disease requiring appropriate diagnoses and prompt treatment
      based on the conditions of the patients and disease.

PMID- 19098398
TI  - [Urological oncology emergencies].
AB  - Urologic emergencies in malignancies are difficult to treat for non-urological
      medical staff because of their anatomical specificity and sensational
      susceptibility. Urological cancer pain involves somatic and neuropathic problems.
      In pelvic malignancies, almost always NSAIDs, micro-2-agonisitic opioids and
      adjuvant analgesics are necessary for pain palliation. The inducements of
      hemorrhagic cystitis are radiation, chemotherapy and tumor invasion. Although
      there are some conservative treatments such as hyperbaric oxygen therapy for
      radiation-induced hemorrhagic cystitis, in emergency circumstances selective
      embolization of the internal iliac artery may be beneficial with fewer side
      effects. In uncontrollable tumor bleeding, palliative radiotherapy(maximum dose
      of 30-36 Gy)is effective. The most important problem in voiding disturbance is
      bladder outlet obstruction. Sometimes patients are treated with alfa-adrenergic
      blockers effectively, but eventually they may need an indwelling catheter.
      Obstructive nephropathy due to malignant ureteral obstruction is an ominous sign
      of progressive disease, especially in pelvic malignancies. The mean survival rate
      of 12 months was less than 30%.

PMID- 19098399
TI  - [Psychiatric symptom in cancer patients requiring immediate management].
AB  - Delirium and major depression are frequently seen in cancer patients. These
      disorders result in a serious situation, sometimes preventing safe medical
      treatment, making for difficult decision making in treatment, causing prolonged
      hospital stays, in association with distress for family members and medical staff
      and other major problems including suicidal behavior. On the other hand,
      underestimation and undertreatment of these psychiatric disorders are often
      reported, so psychiatric problems in cancer, may becomes serious state without
      being noticed by the medical staff. Psychiatric problems in cancer patients have
      multidimensional aspects, not only psychological, but also biological, including
      association of medical treatment, and social aspects like economic problems.
      Furthermore, cancer itself reportedly brings a risk of suicide. In these
      situations, there must be no hesitation in obtaining psychiatric consultation. It
      is important to develop a network between medical staff and psychiatric services,
      to communicate with medical staff about psychiatric problems, and to screen
      psychiatric problem in cancer patients.

PMID- 19098400
TI  - [Treatment for the electrolytic disorders in cancer patients].
AB  - The most frequent electrolytic disorders associating with tumors are
      hypercalcemia and hyponatremia, which should often be dealt with on an emergency
      basis. Hypercalcemia is observed in around 10% of metastatic solid tumors
      including lung, breast, head and neck and renal cancers. In hematological
      malignancies, hypercalcemia is observed with a relatively high incidence in
      malignant lymphoma. Hypercalcemia is caused by bone metastasis or PTH-rP secreted
      from tumors. In other cases, it is induced by calcitriol produced from tumor.
      Hypercalcemia sometimes results in a fatal outcome, and should be carefully
      monitored. Hyponatremia presented as SIADH is sometimes caused by arginine
      vasopressin derived from tumors. In other cases, SIADH is induced with
      chemotherapeutic drugs such as cyclophosphamide and cisplatin. Neither
      hypercalcemia nor hyponatremia has any specific symptoms. Delayed treatment often
      results in severe condition, such as unconsciousness or even death. Therapy for
      hypercalcemia is started by infusion of normal saline, and a patient with severe
      hypercalcemia should be treated with bisphosphonates. Zoledronic acid is the best
      bisphosphonate among them at this present. Treatment of SIADH is started by water
      restriction. In an emergency, treatment with hypertonic saline(3-5%)should be
      considered together with loop diuretics. Demethyl chlorotetracycline is
      considerable in poor response cases, and mozavaptan hydrochloride is applicable
      in case of vasopressin-producing tumors. In any case, inappropriate rapid
      correction of hyponatremia could induce severe brain damage called CPM without
      careful management.

PMID- 19098401
TI  - [Tumor lysis syndrome].
AB  - Recently, the ASCO guideline has added TLS. Prevention and recognition of the
      disease and state are important. Molecular targeting drugs, small molecule
      tyrosine kinase inhibitors and monoclonal antibodies induced rapid regression of
      the tumors and carry a risk of TLS. The recognition of the disease which may have
      a high risk of TLS and laboratory TLS is important.

PMID- 19098402
TI  - [Gemcitabine treatment in patients with stage IV pancreatic cancer and prognostic
      factors for survival of patients with stage IVb(a retrospective survey at 15
      hospitals in Niigata Prefecture)].
AB  - We performed a retrospective survey at 15 hospitals in Niigata Prefecture to
      assess the effectiveness of gemcitabine in patients with stage IV pancreatic
      cancer and to analyze prognostic factors impacting survival in patients with
      stage IVb. The subjects were 244 unresectable or metastatic pancreatic cancer
      patients(IVa 68, IVb 176)who were treated with gemcitabine as first-line therapy.
      The overall response rate was 6.1% and the median survival time(MST)was 194 days.
      The MST of stage IVa(312 days)was double that of stage IVb(167 days). Prognostic
      factors for survival of patients with stage IVb were analyzed(performance status,
      response rate, liver metastasis, peritonitis carcinomatosa, paraaortic lymph node
      metastasis)with the Cox proportional hazards model. Performance status, response
      rate, and liver metastasis were significant factors influencing survival. When we
      compare an effect of other chemotherapy with GEM, we should treat stage IVa and
      stage IVb separately, and subdivision is necessary for stage IVb.

PMID- 19098403
TI  - [Effects of preoperative systemic chemotherapy with respect to expressions of
      hormone receptors and HER2 / neu].
AB  - SUBJECTS: Between August 2003 and January 2008, 35 patients with primary breast
      cancer received preoperative systemic chemotherapy(PSC). METHODS: The subjects
      were divided into 4 groups based on the expressions of ER, PgR, and HER2: luminal
      A and B, HER2, and basal-like groups. FEC75 followed by docetaxel was
      administered preoperatively. However, a regimen with trastuzumab was employed
      after 2006. RESULTS: The subjects consisted of 1 male and 34 females, with a mean
      age of 56.0 years. In 65.7% of these, axillar lymph node metastasis was detected
      before surgery: 13 patients in the luminal A, 4 in the luminal B, 13 in the HER2,
      and 5 in the basal-like groups. A clinical complete response(cCR)was achieved in
      25.7% of the patients, and a partial response in 62.9%; the response rate was
      88.6%. Pathologically, the grade was evaluated as 3 in 14.3% of the patients and
      2 in 48.6%. In the basal-like and HER2 groups, the cCR and pCR rates were higher
      than those in the luminal groups. Combination therapy with trastuzumab was not
      effective in the HER2 or luminal B group. DISCUSSION: This simple classification
      method may be useful for predicting the effects of PSC.

PMID- 19098404
TI  - [Efficacy of gefitinib according to smoking status in non-small cell lung cancer
      patients].
AB  - Gefitinib is a molecular targeting agent and more effective in patients with
      characteristics of oriental ethnicity, female gender, adenocarcinoma and non
      smokers. It is sometimes effective in smokers, but few papers have focused on the
      association between efficacy and smoking history. The aim of this study is to
      evaluate the association between efficacy of gefitinib and patients'
      characteristics, especially smoking history. Between July 2002 and September
      2006, 89 patients were diagnosed as non-small cell lung cancer and administered
      gefitinib. Eighty of them were assessable for efficacy and toxicity of gefitinib.
      Response rate was 16.2% and 39.6%(p=0.031)in smokers and non-smokers. Survival
      was statistically greater in non-smokers. In smokers, there are more cases which
      showed response to gefitinib with a lower smoking index and longer duration after
      smoking cessation. Smoking index and duration after smoking cessation should be
      considered when gefitinib is administered or EGFR mutation analysis is conducted
      in patients with non-small cell lung cancer.

PMID- 19098405
TI  - [Prevention of oxaliplatin-related neurotoxicity by glutathione infusions].
AB  - We have used glutathione for prevention of oxaliplatin-related neurotoxicity with
      reference to the article of Cascinu et al. We investigated oxaliplatin-related
      neurotoxicity in Kariya Toyota General Hospital(KTGH)and compared with the data
      described in the article of Gamelin about the severity of its neurotoxicity.
      Grade 3 neurotoxicity was observed in only 5 of 44 patients(11.4%). The median
      number of cycles and cumulative dose of oxaliplatin were 12 cycles(5-27 /
      cycles)and 802.2(273.2-1,952.4)mg/m(2), respectively, at Grade 3 neuropathy. We
      evaluated retrospectively neuro-toxicity grade at cumulative oxaliplatin doses of
      approximately 500-520 mg/m(2). The severity of neurotoxicity observed in KTGH was
      significantly lower than in the group without Ca/Mg. We found no difference
      between the group with glutathione and / with Ca/Mg. Glutathione infusions seemed
      to prevent oxaliplatin-related neurotoxicity.

PMID- 19098406
TI  - [Single nucleotide polymorphism analysis in the GSTP1 and ABCC2 genes about
      neuropathy by the Oxaliplatin].
AB  - The appearance of neuropathy that is a harmful phenomenon of Oxaliplatin, the key
      drug of FOLFOX, is strongly concerned in individual pharmacological variability.
      Further more, the frequency of neuropathy appearance was reported to be 74.3%. In
      this study, we examined a correlation between GSTP1(342G>A)and ABCC2(1249G>A)of
      genetic polymorphism. The mean FOLFOX drug dosage was 8.6 times. The first,
      second and third line treatment was 36, 32 and 9 cases, respectively. Then, the
      50% survival duration of each treatment was 801, 360 and 328 days, respectively.
      These results showed that the first line treatment was highly lengthened the
      survival duration compared with the second and third line treatment. The response
      rate was 24.2%, and the lesion control rate was 74.2%. However, some of the
      toxicities we have seen included the followings: acute nervousness; 74.3%,
      chronic nervousness; 67.1%, allergic reaction; 26.3%, blood toxicity development;
      68.4% and digestive organ symptom; 30.3%. The reasons for change in treatment
      were due to PD 41.6% and toxicity 51.4%, and that 45.9% of the latter was caused
      by neuropathy. As for a successful rate of the treatment, the wild type and
      hetero type of GSTP1, a metabolism enzyme of Oxaliplatin, were 53.3% and 41.7%,
      respectively. As for a correlation between the dose frequency and GSTP1 SNP was
      p=0.57, and that a correlation between the dose frequency and ABCC2 was p=0.11.
      We confirmed that a curative effect of the first line treatment of FOLFOX was
      high, and that the cases in which the treatment was terminated due to neuropathy
      prolonged the survival duration. It is important to control the appearance of
      toxicity in order to continue the treatment. The SNP analysis of the ABCC2
      protein may become an index of the treatment for continuation.

PMID- 19098407
TI  - [Fungal blood stream infection, its pathogen and antifungal susceptibility in
      cancer patients].
AB  - It is important to correctly diagnose fungal bloodstream infection in cancer
      patients. Antifungal susceptibility testing (AST)supplies useful information for
      the management of invasive fungal infection. We analyzed fungi isolated from
      blood samples in Shizuoka Cancer Center over a period of 6 years, and detected 59
      strains including yeast(57 isolates) and mold(Aspergillus fumigatus, Scedosporium
      sp). The clinical background was reviewed using the medical record. The major
      fungi isolated from blood were Candida albicans(39.0%), followed by C.
      glabrata(22.0%), C. parapsilosis (20.3%), and C. tropicalis(13.6%). AST was
      carried out for 32 strains out of 59, according to the National Committee of
      Clinical Laboratory Standards (NCCLS)M-27-A-2 method. Among 32 strains, 7
      isolates were resistant to fluconazole and 8 to itraconazole. Through the
      research period, the distribution of MIC values for azole agents did not change
      widely; however, the values for micafungin increased between the former and
      latter periods. In order to estimate the efficacy of antifungal agents, it is
      thought that continuous monitoring and the establishment of a standard method to
      evaluate the sensitivity of antifungal drugs are necessary.

PMID- 19098408
TI  - [A successful case of advanced nasal adenocarcinoma treated with tumor dormancy
      therapy with S -1 alone].
AB  - We report a 65-year-old female case of low-grade non-intestinal type
      adenocarcinoma of the nasal cavity with bilateral metastases to the cervical
      lymph nodes(T3N2cM0: Stage IV A). Chemoradiotherapy administered as first-line
      therapy yielded only a partial response in the primary tumor and metastatic
      lesions, and subsequent chemotherapy with S-1(at a dose of 80 mg per day)alone
      was applied as tumor dormancy therapy(TDT)on an outpatient basis. Adverse events
      during S-1 medication were limited to a decrease in leukocyte count and
      hemoglobin level, both of which were grade 1. The tumor has not enlarged, and the
      patient has survived 29 months since the beginning of chemotherapy with S-1 alone
      without any decrease in quality of life. Although the effectiveness of S-1 for
      adenocarcinoma of the head and neck has not been fully demonstrated, S-1 might be
      useful in patients with advanced head and neck adenocarcinoma for the purpose of
      TDT.

PMID- 19098409
TI  - [Case report of advanced esophageal cancer patient surviving for a long time
      after asynchronous chemoradiation].
AB  - We have present a case of advanced esophageal cancer(Stage IVb), that has
      survived for 7 years and 4 months after systemic hemotherapy followed by
      radiation therapy. The patient is a female, 63 years old. We diagnosed her with
      esophageal cancer Stage IVb with direct invasion to the main bronchus and the
      metastatic lesion to the right lobe of thyroid gland. Then we initiated low-dose
      FP therapy(5-FU 500 mg/day/body, day 1-7, CDDP 10 mg/day/body day 1-5), and then
      continued UFT+CDDP(UFT 400 mg/day, CDDP 10 mg/day). About 4 years and eight
      months after chemotherapy we detected swelling of a mediastinal lymph node, which
      was assessed as a recurrence. Then we started the radiation therapy. Since she
      has received UFT, we have not seen any recurrences.

PMID- 19098410
TI  - [A case of advanced gastric cancer with pulmonary carcinomatous lymphangitis
      responding remarkably to combination chemotherapy of docetaxel, CDDP and S-1].
AB  - A 31-year-old woman suffering from stomach pain was admitted to our hospital, and
      diagnosed with unresectable advanced gastric cancer. She was initially treated
      with combination therapy of S-1 and CDDP, and a partial response was achieved.
      After two courses of the chemotherapy, however, she complained of dyspnea, and
      pulmonary carcinomatous lymphangitis was confirmed by computed tomography. As
      second-line chemo-therapy, we attempted combination therapy with docetaxel, CDDP
      and S-1(DCS). After one course of the combination therapy, a remarkable response
      in the pulmonary carcinomatous lymphangitis was achieved. Treatment of patients
      with advanced gastric cancer associated with pulmonary carcinomatous lymphangitis
      is quite difficult and there is no scientific evidence to select anti-cancer
      drugs for these patients. We concluded that DCF could be a useful regimen for
      patients with gastric cancer associated with pulmonary carcinomatous
      lymphangitis.

PMID- 19098411
TI  - [A case of advanced gastric cancer successfully treated by S-1 based
      chemotherapy].
AB  - A 57-year-old patient presented with a loss of appetite and vomiting.
      Gastrointestinal endoscopy revealed advanced gastric cancer with pyloric
      stenosis, and CT scan showed multiple liver metastases and paraaortic lymph node
      metastases. A gastrojejunostomy was performed because of invasion of the
      pancreas. After 5 courses of S-1 plus cisplatin, both the primary lesion and the
      paraaortic lymph nodes were reduced in size, and the liver metastases
      disappeared. Subsequently, a distal gastrectomy was performed. No recurrence was
      seen for sixteen months from treatment with the oral anticancer drug S-1. At 16
      months after second surgery, progression of paraaortic lymph nodes was recognized
      again, and S-1 plus paclitaxel was administered. After 7 courses of S-1 plus
      paclitaxel, paraaortic lymph nodes became undetectable. This report describes a
      case of unresectable advanced gastric cancer treated by S-1 based chemotherapy
      and surgical method, which resulted in long survival and improvement in quality
      of life.

PMID- 19098412
TI  - [A case of advanced gastric cancer showing high serum CYFRA21-1 level responding
      to chemotherapy with S-1].
AB  - The patient was a 75-year-old man whose complaint was back pain and appetite
      loss. He was diagnosed with unresectable advanced gastric cancer due to multiple
      liver metastases and direct invasion of pancreas and spleen. He underwent
      gastrostomy because of esophageal stenosis, and we administered S-1 80 mg/body(4
      weeks administration and 2 weeks rest)to the patient through a gastrostogavage
      tube. On blood examination, the serum level of CYFRA21- 1 was significantly high,
      while those of CEA and CA19-9 were within normal ranges. After the first course
      of this chemotherapy, the serum CYFRA21-1 level significantly decreased with
      reduction of the cancer. After the second course, it sensitively increased before
      image views detected the progression of the cancer. This case shows that CYFRA21-
      1 could be a useful tumor marker of advanced gastric cancer.

PMID- 19098413
TI  - [Regression of metastatic hepatic cancer from gastric cancer by polysaccharide K
      and UFT administration--a case report].
AB  - Various treatments for hepatic metastasis of gastric cancer have been attempted,
      but problems remain with respect to long-term effectiveness and recurrence. Case
      reports have indicated the tumor regression effect of polysaccharide
      K(PSK)combined with chemotherapy, and meta-analysis has shown that PSK combined
      with chemotherapy improves the prognosis compared to chemotherapy alone. However,
      marked improvement of disease following PSK administration is rarely reported. We
      report a case of hepatic metastasis of gastric cancer in which low-dose UFT and
      PSK therapy resulted in regression of metastatic hepatic lesions and improvement
      of tumor markers. A 78-year-old man had synchronous hepatic metastasis of gastric
      cancer. Gastrectomy and microwave coagulation therapy using Microtase were
      conducted, followed by postoperative adjuvant chemotherapy with UFT 300 mg/day.
      Recurrences of metastatic hepatic lesion and new hepatic lesion were observed 6
      months after surgery. Addition of PSK to UFT chemotherapy was selected as the
      treatment for recurrences, resulting in disappearance of the hepatic lesions and
      normalization of tumor markers. The patient is alive without recurrence at this
      writing, 38 months after surgery.

PMID- 19098414
TI  - [A long survival case of unresectable pancreatic cancer by chemoradiotherapy with
      gemcitabine as key drug].
AB  - A 64-year-old man complaining of left hypochondriac pain visited our hospital. He
      was diagnosed as locally advanced unresectable cancer of the pancreatic body over
      4 cm in size, because the pancreatic cancer involved the main artery and portal
      vein. Although chemotherapy of gemcitabine(GEM)(1.2 g/body/week)was started, he
      developed meningeal carcinomatosis after 2 courses of GEM. The size of the
      primary lesion decreased at this period, and total brain irradiation was selected
      to treat the meningeal carcinomatosis. He sequentially received GEM alone
      afterward until radiotherapy was performed for the progression of the primary
      lesion 24 months after the diagnosis. Although GEM alone was continued
      thereafter, vertebral metastases were detected 30 months following the diagnosis.
      He was treated with combined chemotherapy of GEM and S-1 that was effective.
      Finally, he died of peritoneal dissemination 42 months after diagnosis. The dose
      of GEM was reduced during the radiotherapy, and the total dose was 113.2 g.

PMID- 19098415
TI  - [Elderly patient with metastatic gallbladder cancer treated by cisplatin,
      epirubicin and continuous infusion 5-fluorouracil].
AB  - An 80-year-old woman, who was followed as an A-bomb victim, was diagnosed to have
      advanced gallbladder cancer with liver metastasis on December, 2005. Due to her
      advanced age, her previous doctor recommended the best supportive care.
      Therefore, her general condition was good, so we decided to treat her with
      cisplatin, epirubicin and continuous infusion of 5-fluorouracil(CEF therapy). She
      was given 5-fluorouracil 500 mg/body per day via continuous infusion on days 1 to
      5, cisplatin 50mg body and epirubicin 20mg body on day 1 every 28 days, and these
      dosages have been reduced. CEF therapy was started from February, 2007. Primary
      lesion and liver metastasis decreased remarkably after completion of 2 cycles,
      and we judged it as a complete response. After 10 cycles, lung metastasis was
      found by CT scan in August, 2007. We tried chemotherapy with gemcitabine as a
      second-line treatment. The result of gemcitabine was again a progressive disease,
      so we switched her regimen to S-1 as a third-line treatment on January, 2008.
      Chemotherapy is continued by the outpatient care now, 25 months after the medical
      treatment started. The present result suggests that CEF therapy may be useful for
      metastatic gallbladder cancer.

PMID- 19098416
TI  - [A case of peritonitis carcinomatosa from goblet cell carcinoid of the appendix
      treated by intraperitoneal paclitaxel and systemic S-1 chemotherapy].
AB  - Goblet cell carcinoid of the appendix is a rare neoplasm and clinically tends to
      take a malignant course. Most cases are young and early stage, and the surgical
      strategy is available. But appropriate chemotherapy for inoperable cases with
      peritoneal dissemination is not established. A 77-year-old woman with a past
      history of appendectomy was admitted to our hospital complaining of abdominal
      fullness. Abdominal computed tomography showed massive ascites and slight
      contrast enhancement of appendix. A tumor was found by colonoscopic examination
      at the orifice of vermiform and was diagnosed pathologically as goblet cell
      carcinoid of the appendix. Laparoscopy showed multiple peritoneal dissemination.
      We performed intraperitoneal paclitaxel(PTX)administration at 70 mg/m(2) week
      without any resection of the tumor. Ascites were reduced immediately, but drug
      induced interstitial pneumonia occurred due to PTX. After steroid therapy, we
      switched to systemic S-1 therapy. For about one year, her tumor was controlled
      but became worse thirteen months after diagnosis and died. It is thought that
      intraabdominal paclitaxel administration and systemic S-1 therapy can be one of
      appropriate forms of chemotherapy for inoperable peritoneal carcinomatosis from
      goblet cell carcinoid of appendix.

PMID- 19098417
TI  - [A case of advanced sigmoid colon cancer with peritoneal dissemination responding
      to FOLFOX4 therapy].
AB  - A 62-year-old woman complained of thin feces, lower blood and abdominal pain, and
      she was diagnosed as having bowel obstruction due to sigmoid colon cancer.
      Abdominal CT showed peritoneal dissemination and ascites on the surface of liver.
      The serum CEA levels were 663.7 ng/mL. We established a diagnosis of unresectable
      sigmoid colon cancer accompanied by severe peritoneal dissemination and therefore
      performed only transverse colostomy in April, 2006. Pathological examination of
      omental dissemination demonstrated moderately-differentiated adenocarcinoma.
      FOLFOX4 therapy was started on April, 2006. Primary lesion decrease and release
      from bowel obstruction after 4 cycles was judged as a partial response. The
      partial response continued, and the serum CEA decreased 18.5 ng/mL after
      completion of 16 cycles, but grade 3 neuropathy occurred. We started S-1 as
      second-line chemotherapy in May, 2007. There was primary lesion re-growth after 4
      cycles, so we changed to S-1+CPT-11 therapy. The adverse events were grade 3
      neuropathy and leucopenia throughout the course. Chemotherapy is now continued on
      an outpatient basis, 24 months after the medical treatment started. FOLFOX4
      therapy is useful for patients with advanced colon cancer accompanied by
      peritoneal dissemination.

PMID- 19098418
TI  - [Doxifluridine, medroxyprogesterone acetate and cyclophosphamide (DMpC)
      combination therapy is effective against recurrent triple negative breast cancer-
      a case report].
AB  - We report a postmenopausal recurrent breast cancer patient with triple negative
      disease who presented with right recurrent nerve palsy. Nine years previously,
      she had undergone a mastectomy. FDG-PET scan revealed neck lymph node metastases
      from the breast cancer. The recurrent nerve palsy was thus considered to have
      been caused by the lymph node metastases. The patient was orally administered
      DMpC (doxifluridine, medroxyprogesterone acetate and cyclophosphamide)
      combination therapy. This resulted in a remarkable response after five months,
      with the recurrent nerve palsy completely disappearing at six months. No side
      effects from the treatment were observed. The patient was well and the treatment
      was being continued without relapse at nine months. Oral anti-cancer treatments
      such as DMpC appear to have few side effects and might be an effective treatment
      option for recurrent breast cancer patients with triple negative disease.

PMID- 19098419
TI  - [Two cases of stomach primary diffuse large B cell lymphoma remitted by
      Helicobacter pylori eradication therapy].
AB  - CASE 1: The patient was a 71-year-old woman who came to our hospital for
      epigastric checkup. Upper gastrointestinal endoscopy showed an ulcerative lesion.
      Because Helicobacter pylori was positive, eradication therapy was given. As a
      result of biopsy, a diagnosis of diffuse large B cell lymphoma was made and she
      was introduced to our department. The lesion showed improvement with upper
      gastrointestinal endoscopy after eradication therapy, and no lymphoma cells were
      confirmed. She has been doing well without a recurrence. CASE 2: The patient was
      a 49-year-old man who had an anomaly noted with upper gastrointestinal endoscope.
      Then he was introduced to our hospital. Helicobacter pylori eradication therapy
      was performed because MALT lymphoma was suspected by a previous hospital. The
      only evidence of chronic gastritis was revealed with upper gastrointestinal
      endoscope at our hospital, but no lymphoma cells. As we reviewed a specimen again
      before Helicobacter pylori eradication therapy, the diagnosis was diffuse large B
      cell lymphoma because lymphoma cells were large, the MIB1 index was high, and Bcl
      6 was positive. He has been doing well without a recurrence. As for a treatment
      of localized diffuse large B cell lymphoma, chemo-radiotherapy has generally been
      performed. However, we reported here two cases of gastric diffuse large B cell
      lymphoma regression that were confirmed after Helicobacter pylori eradication
      therapy, and CR was maintained without a recurrence.

PMID- 19098420
TI  - [Long-term complete remission in primary plasma cell leukemia after treatment
      with VAD chemotherapy and tandem autologous peripheral blood stem cell
      transplantation].
AB  - A 54-year-old woman visited our hospital with the chief complaints of generalized
      pain and thirst. Through hematologic and bone marrow examination, we diagnosed
      her illness as primary plasma cell leukemia. Three courses of VAD (vincristine,
      adriamycin and dexamethasone)therapy induced complete remission. Afterward, the
      patient received high-dose cyclophosphamide (4 g/m(2))for hematopoietic stem cell
      mobilization, and peripheral blood hematopoietic stem cells were collected 14
      days later from the start of chemotherapy. Thereafter, the patient received 2
      courses of high-dose melphalan (200 mg/m(2)), followed by tandem autologous
      peripheral blood stem cell transplantation. The patient developed no adverse
      events other than fever and stomatitis during the 2 transplantation courses.
      Fifty-six months after the transplantations, she remains in complete remission
      with continuous oral administration of bisphosphonate alone. Taken together,
      although primary plasma cell leukemia is a rare hematologic malignancy with poor
      prognosis, the intensive chemotherapy followed by tandem autologous peripheral
      blood stem cell transplantation may well improve the clinical outcome.

PMID- 19098421
TI  - [Changes in peripheral neuropathy and platinum concentrations in patients
      undergoing surgery following modified FOLFOX6 therapy].
AB  - BACKGROUND: Gornet et al.(2002) reported that patients who received chemotherapy
      containing oxaliplatin for metastatic colorectal cancer experienced exacerbation
      of neurotoxicity after surgical resection and suggested that the possible
      mechanism behind exacerbation of neurotoxicity was perioperative transfer of
      accumulated platinum from the red blood cells into the plasma. However, no
      further reports about this issue have been published. PATIENTS AND METHODS: We
      investigated changes of neurotoxicity after resection in three patients who
      received modified FOLFOX6 therapy prior to surgery. In addition, changes of the
      total plasma, ultrafiltrate, and erythrocyte platinum levels were determined by
      inductively coupled plasma mass spectrometry. RESULTS: Exacerbation of
      neurotoxicity was not seen in any of the patients postoperatively. The platinum
      concentrations of all samples did not change significantly from before surgery to
      4, 24, and 48 hours postoperatively. CONCLUSION: Further assessment of patients
      is needed to draw a definite conclusion, but our preliminary data suggest that
      the risk of neurotoxicity exacerbation due to perioperative changes of the
      platinum pool is low.

PMID- 19098422
TI  - Using kinomics to delineate signaling pathways: control of CRTC2/TORC2 by the
      AMPK family.
AB  - The classical role of AMP-activated protein kinase (AMPK) as an energy status
      sensor is expanding to include other members of the AMPK family. Recent genetic
      and cell biological evidence points to a role for MAP/microtubule affinity
      regulating kinase 2 (MARK2/EMK/Par1b) in the regulation of metabolic events as
      well as in the control of CREB-dependent transcription activated by glucose in
      pancreatic islet beta cells. We have recently developed an in vitro kinase
      screening platform to identify novel kinase:substrate pairs, the building blocks
      of signal transduction pathways. Application of this technology led us to
      identify MARK2 as the kinase that targets a novel glucose-regulated
      phosphorylation site on Transducer of Regulated CREB Activity 2 (TORC2, referred
      to as CREB-Regulated Transcriptional Coactivator 2, or CRTC2), a transcriptional
      coactivator essential for CREB activity in beta cells. We discuss these recent
      developments and suggest a model whereby members of the AMPK family integrate
      numerous signals to coordinate energy metabolism and cellular polarity with gene
      expression to regulate cell function/proliferation.

PMID- 19098423
TI  - PKC delta signaling: a dual role in regulating hypoxic stress-induced autophagy
      and apoptosis.
AB  - The protein kinase C (PKC) family of serine/threonine kinases regulates diverse
      cellular function, including cell death, proliferation and survival. In
      particular, PKC delta governs the cellular homeostatic response against hypoxic
      stress. Autophagy, a lysosome-dependent degradative pathway, and apoptosis are
      two fundamental cellular pathways that respond to stress conditions, such as
      hypoxia, oxidative stress and nutrient starvation. Recently, we uncovered a novel
      role for PKC delta in the early stage of hypoxic response where PKC delta
      activates autophagy by promoting JNK1-mediated Bcl-2 phosphorylation and
      dissociation of the Bcl-2/Beclin 1 complex. Whereas acute hypoxic stress promotes
      autophagy, we have previously reported that prolonged hypoxic stress caused the
      cleavage of PKC delta by caspase-3, resulting in the nuclear translocation of a
      constitutively active catalytic fragment of PKC delta, PKC delta-CF. Moreover,
      PKC delta-CF also serves a feed-forward function for the reciprocal PKC delta and
      caspase-3 proteolytic activation. Here, we discussed the requirement for PKC
      delta and JNK1 for hypoxia-induced autophagy, and the kinetic relationship among
      Bcl-2/Beclin 1 interaction, caspase-3 activation and the steady-state level of
      Beclin 1 during hypoxic exposure. Based on these results, we propose a model for
      understanding the PKC delta-dependent crosstalk mechanisms between autophagy and
      apoptosis, both induced by hypoxic stress. These findings collectively support a
      pivotal role for PKC delta in regulating hypoxic stress with hitherto
      unappreciated significance.

PMID- 19098424
TI  - Stem cell marker expression and proliferation and apoptosis of vascular smooth
      muscle cells.
AB  - Vascular endothelial Flt-1 and other stem cell markers are variably expressed in
      vascular smooth muscle cells (SMCs) during normal and pathological conditions,
      but their biological role remains uncertain. In normal rat aorta, rare flt-1+ and
      c-kit+ SMCs were detected. Fifteen days after injury, 61.8 +/- 3.8, 45.7 +/- 3%
      of the intimal cells resulted flt-1+ and c-kit+ and expressed low level of alpha
      smooth muscle actin; CD133+ cells were 5.6 +/- 0.7%. BrDU+/flt-1+ largely
      predominated in the neointima, whereas BrDU+/CD133+ cells were rare. Forty-five
      and sixty days after injury, intimal proliferation such as BrDU+ cells was
      greatly reduced. After sixty days, intimal stem marker expression had almost
      disappeared whereas alpha-smooth muscle actin was restored. Flk-1 and Oct-4 SMC
      immunodection was consistently negative. In vitro, intimal cells obtained fifteen
      days after injury exhibited an epithelioid phenotype and increased flt-1 and c
      kit protein and mRNA and low smooth muscle markers compared to spindle-shaped
      medial and intimal SMCs obtained after sixty days. Epithelioid clones,
      independently from layer of origin, were similar in stem cell marker expression.
      The anti-flt-1 blocking antibody added to epithelioid SMC cultures reduced serum
      deprived apoptosis and migration but not PDGF-BB-induced proliferation, and
      increased cell-populated collagen lattice contraction. In conclusion, vascular
      SMC stem marker expression was variable, chronologically modulated and prevalent
      in epithelioid populations and clones; among stem markers, flt-1 expression
      critically regulates intimal SMC response to microenviromental changes.

PMID- 19098425
TI  - Insulin-like growth factor-1 inhibits STS-induced cell death and increases
      functional recovery of in vitro differentiated neurons.
AB  - NG108-15 cells differentiate into neurons by 1 mM sodium butyrate (NaB)
      treatment. Differentiated cells resulted more resistant to staurosporine (STS)
      than proliferating cells. In particular, STS treatment decreased Bcl-2 and Bcl
      x(L) content in mitochondria of proliferating cells, but not in mitochondria of
      differentiated cells. Bad was phosphorylated and downregulated only in
      differentiated cells. Bax accumulated in the mitochondria of proliferating but
      not differentiated cells. Mitochondrial release of cytochrome c was observed in
      proliferating cells, whereas mitochondria of differentiated cells retained
      cytochrome c. Proliferating cells treated with STS accumulated Endo G and AIF in
      the nucleus. By contrast, differentiated cells did not show such nuclear
      accumulation. Treatment of differentiated cells with Insulin-like Growth Factor-1
      (IGF-1) and STS resulted in a 17.1% increase of cell viability. The survival role
      of IGF-1 was demonstrated by treating differentiated cells with an anti-IGF-1
      neutralizing antibody. Such treatment significantly increased STS-induced cell
      death. Electrophysiology studies showed that in STS-treated cells membrane
      potential oscillations were reduced in amplitude and did not give rise to
      spontaneous action potentials (APs). However, the percentage of cells yielding
      overshooting APs returned to control values after STS removal. It is concluded
      that neuronal differentiation of NG108-15 cells induces resistance to apoptotic
      cell death and that IGF-1 plays a central role in sustaining this mechanism.

PMID- 19098426
TI  - The let-7 microRNA target gene, Mlin41/Trim71 is required for mouse embryonic
      survival and neural tube closure.
AB  - In the nematode Caenorhabditis elegans, the let-7 microRNA (miRNA) controls the
      timing of key developmental events and terminal differentiation in part by
      directly regulating lin-41. C. elegans lin-41 mutants display precocious cell
      cycle exit and terminal differentiation of epidermal skin cells. lin-41
      orthologues are found in more complex organisms including both mice and humans,
      but their roles are not known. We generated Mlin41 mouse mutants to ascertain a
      functional role for Mlin41. Strong loss of function Mlin41 gene-trap mutants
      demonstrated a striking neural tube closure defect during development, and
      embryonic lethality. Like C. elegans lin-41, Mlin41 also appears to be regulated
      by the let-7 and mir-125 miRNAs. Since Mlin41 is required for neural tube closure
      and survival it points to human lin-41 (HLIN41/TRIM71) as a potential human
      development and disease gene.

PMID- 19098427
TI  - T cell survival and function requires the c-Abl tyrosine kinase.
AB  - C-Abl (Abl) regulates multiple cellular processes, including proliferation,
      survival, shape determination and motility, and participates in cellular
      responses to genotoxic and oxidative stress stimuli. Mice lacking Abl exhibit
      retarded growth, osteoporosis and defects in the immune system resulting in
      lymphopoenia and susceptibility to infections, leading to early death. To define
      the role of Abl in the regulation of adult T cells we ablated Abl exclusively in
      T cells by generating mice with floxed abl alleles and expressing an Lck-Cre
      transgene (Abl-T(-/-)). These mice exhibited thymic atrophy and abnormally
      reduced T cell numbers in the periphery. The thymic atrophy was caused by
      increased susceptibility of thymocytes to cell death. Importantly, Abl deficient
      T cells displayed abnormally reduced response to mitogenic stimulation in vitro.
      Consequently, Abl-T(-/-) mice exhibited impaired ability to reject syngeneic
      tumor, to induce T-mediated tumor cell killing, and to generate anti-tumor
      antibodies. These results demonstrate a cell-autonomous role for Abl in T cell
      function and survival.

PMID- 19098428
TI  - Positional analyses of BRCA1-dependent expression in Saccharomyces cerevisiae.
AB  - Mutations in BRCA1 account for a significant proportion of hereditary breast and
      ovarian cancers, but analysis of BRCA1 function is complicated by pleiotropic
      effects and binding partners (Pol II holoenzyme and transcription factors,
      chromatin remodelers, recombination complexes and E3 ligases). In vertebrate
      cells, efforts to elucidate BRCA1 transcriptional effects have focused on
      specific genes or restricted portions of the genome-limiting analyses of BRCA1
      effects on adjoining DNA sequences and along chromosome lengths. Here, we use
      microarray analyses on the genetically tractable yeast cell system to elucidate
      BRCA1-dependent genomewide positional effects on both gene induction and
      repression. Yeast responses may be of clinical relevance based on findings that
      BRCA1 severely diminishes yeast growth kinetics but that BRCA1 mutated at sites
      identified from breast tumors is no longer able to retard yeast cell growth
      kinetics. Our analysis suggests that BRCA1 acts through both transcription
      factors to upregulate specific loci and chromatin remodeling complexes to effect
      global changes in gene expression. BRCA1 also exhibits gene repression
      activities. Cluster-functional analysis reveals that these repressed factors are
      required for mitotic stability and provide a novel molecular explanation for the
      conditional lethality observed between BRCA1 and chromosome segregation genes.

PMID- 19098429
TI  - Chronic lymphocytic leukemia and treatment resistance in cancer: the role of the
      p53 pathway.
AB  - The importance of studying p53 pathway defects in CLL has been fostered by the
      demonstration of the fundamentally different clinical course of patients with 17p
      deletion, where the clinical course is, contrary to most patients with CLL, very
      poor. The demonstration of the resistance to chemotherapy and mutation of the
      remaining TP53 allele explains the clinical presentation of CLL with 17p
      deletion. Here we review recent evidence that TP53 mutation in the absence of the
      deletion of 17p shows a similar clinical and biological course in CLL. In
      addition, there is growing evidence that alterations of other components of the
      DNA damage response pathway, such as ATM and miR34a are associated with treatment
      resistance.

PMID- 19098430
TI  - The Epstein-Barr virus replication and transcription activator, Rta/BRLF1,
      induces cellular senescence in epithelial cells.
AB  - Epstein-Barr Virus (EBV) replication and transcription activator (Rta/BRLF1) is
      an immediate-early transcription factor that controls the conversion of the
      latent viral genome into one undergoing lytic replication. By using a doxycycline
      inducible expression system, the present study demonstrates that EBV Rta
      efficiently elicits growth arrest in the human epithelial cell line HEK293. In
      cells arrested by EBV Rta, the expression of p21 (CDKN1A), p27 (CDKN1B) and
      cyclin E were increased. In contrast, the levels of cyclin D1, CDK4 and CDK6 were
      sharply decreased. Activation of the host cell DNA damage response (DDR),
      indicated by the increasing phosphorylation of H2AX and p53 Ser15, was observed
      on day 3 and day 5 after EBV Rta expression, respectively. Finally, EBV Rta
      arrested cells exhibited strong senescence-associated beta-galactosidase staining
      on day 10 after doxycycline induction. Together, these results indicate that, in
      addition to triggering viral lytic replication in epithelial cells, EBV Rta
      concurrently initiates a cellular senescence program that was previously
      undocumented. This finding, showing Rta may be centrally involved in inducing a
      host cell state amenable to efficient viral reproduction, in addition to its
      previously characterized regulation of viral transcription, provides new
      perspectives in understanding EBV pathogenesis.

PMID- 19098431
TI  - APC/C- and Mad2-mediated degradation of Cdc20 during spindle checkpoint
      activation.
AB  - The spindle assembly checkpoint (SAC) is an important mechanism that prevents the
      separation of sister chromatids until the microtubules radiating from the spindle
      poles are correctly attached to the kinetochores. Cdc20, an activator of the
      Anaphase Promoting Complex/Cyclosome (APC/C), is known as a major downstream
      target for inhibition by the SAC through the binding of mitotic checkpoint
      proteins, such as Mad2 and BubR1. Here, we report that the SAC negatively
      regulates the stability of Cdc20 by targeting it for proteasome-dependent
      degradation. Once the checkpoint is activated by spindle poisons, a major
      population of Cdc20 is degraded via APC/C, an event that requires the binding of
      Cdc20 to Mad2. We propose that the degradation of Cdc20 represents a critical
      control mechanism to ensure inactivation of APC/C(Cdc20) in response to the SAC.

PMID- 19098432
TI  - Epigenetics and cancer without genomic instability.
AB  - Genomic instability is often considered a hallmark of cancer. However, it remains
      unclear whether chromosomal disorganization is most frequently a cause or a
      consequence of tumorigenesis. The fact that subsets of many cancers lack
      chromosomal or microsatellite instability argues against the hypothesis that
      genomic instability plays an essential role in the initiation and maintenance of
      oncogenesis. Cancer-specific, epigenetically-based changes in gene expression
      caused by abnormalities in DNA methylation, in histone modifications, and in
      nucleosome positioning are gaining recognition as driving events in
      tumorigenesis. But are these changes merely a small piece of the oncogenesis
      puzzle or could they be the major component, or even sufficient for cancer? Here
      we discuss evidence that the progression of aggressive cancers can be driven by
      epigenetic events without genomic instability.

PMID- 19098433
TI  - Interaction between voltage-gated sodium channels and the neurotoxin,
      tetrodotoxin.
AB  - Tetrodotoxin (TTX) is a potent toxin that specifically binds to voltage gated
      sodium channels. TTX binding physically blocks the flow of sodium ions through
      the channel, thereby preventing action potential (AP) generation and propagation.
      TTX has different binding affinities for different sodium channel isoforms. These
      differences are imparted by amino acid substitutions. Such substitutions confer
      TTX resistance to a variety of species. Tetrodotoxin resistance, however, may
      come at a cost to performance caused by changes in the biophysical properties
      and/or ion selectivity of the TTX resistant sodium channels. We here review the
      properties of sodium channels and their interaction with TTX, and look at some
      special examples of TTX resistant channels wherein the benefit of toxin
      resistance may be offset by other behavioral costs.

PMID- 19098434
TI  - The 30th anniversary Crete fly meeting: from individual molecules to 12 genomes,
      and beyond.
AB  - The 16(th) Biennial Meeting of the EMBO-Sponsored International Workshop on the
      Molecular and Developmental Biology of Drosophila was held in Kolymbari, Crete
      from June 23 to June 28, 2008. As in previous years, the weather was hot, the
      Mediterranean Sea was clear and blue and the presentations were exciting and
      illuminating.

PMID- 19098435
TI  - Fly-TILL: reverse genetics using a living point mutation resource.
AB  - Mutagenesis with ethylmethanesulfonate (EMS) has been the standard for
      traditional genetic screens, and in recent years has been applied to reverse
      genetics. However, reverse-genetic strategies require maintaining a viable
      germline library so that mutations that are discovered can subsequently be
      recovered. In applying our TILLING (Targeting Induced Local Lesions IN Genomes)
      method to establish a Drosophila reverse-genetic service (Fly-TILL), we chose to
      screen the Zuker lines, a large collection of EMS-mutagenized second- and third
      chromosome balanced lines that had been established for forward-genetic
      screening. For the past four years, our Fly-TILL service has screened this
      collection to provide approximately 150 allelic series of point mutations for the
      fly community. Our analysis of >2000 point mutations and indels have provided a
      glimpse into the population dynamics of this valuable genetic resource. We found
      evidence for selection and differential recovery of mutations, depending on
      distance from balancer breakpoints. Although this process led to variable
      mutational densities, we have nevertheless been able to deliver potentially
      valuable mutations in genes selected by Fly-TILL users. We anticipate that our
      findings will help guide the future implementation of point-mutation resources
      for the Drosophila community.

PMID- 19098436
TI  - Prion infection: seeded fibrillization or more?
AB  - The prion infection is a conversion of host encoded prion protein (PrP) from its
      cellular isoform PrP(C) into the pathological and infectious isoform PrP(Sc); the
      conversion process was investigated by in vitro studies using recombinant and
      cellular PrP and natural PrP(Sc). We present a brief summary of the results
      determined with our in vitro conversion system and the derived mechanistic
      models. We describe well characterized intermediates and precursor states during
      the conversion process, kinetic studies of spontaneous and seeded fibrillogenesis
      and the impact of the membrane environment.

PMID- 19098437
TI  - The peculiar interaction between mammalian prion protein and RNA.
AB  - In the past decade, the interaction between prions and nucleic acids has garnered
      significant attention from the scientific community. for many years, the
      participation of RNA and/or DNA in prion pathology has been largely ruled out by
      the "protein-only" hypothesis, but this is now being reconsidered. Experimental
      data now indicate that nucleic acids (particularly RNA), besides being carriers
      of genetic information, function as important key components during development,
      physiological responsiveness and cellular signaling. This revelation has brought
      a new perspective to prion pathology. Here we discuss the role of RNA molecules
      in prion protein aggregation and the resulting cellular toxicity. We combine our
      most recent findings with existing literature to shed new light on this exciting
      field of research.

PMID- 19098438
TI  - Cellular prion protein null mice display normal AMPA receptor mediated long term
      depression.
AB  - Cellular prion protein (PrP(C)) appears to be involved in numerous physiological
      processes. We have recently shown a novel modulation of NMDA receptors by PrP(C)
      that results in neuroprotection via silencing of NMDA receptors containing NR2D
      subunits, whereas no effects on AMPA receptor function could be observed
      (Khosravani, et al. J Cell Biol 2008; 181:551). Here we show that PrP-null mice
      show a normal response to long-term depression stimuli requiring AMPA receptor
      activity, thus further supporting our previous findings of a selective action on
      NMDA receptors among ionotropic glutamate receptors.

PMID- 19098439
TI  - Amyloid-like properties of Saccharomyces cerevisiae cell wall glucantransferase
      Bgl2p: prediction and experimental evidences.
AB  - Glucantransferase Bgl2p is a major conserved cell wall constituent described for
      a wide range of yeast species. In the baker's yeast Saccharomyces cerevisiae it
      is the only non-covalently bound cell wall protein that cannot be released from
      cell walls by sequential SDS and trypsin treatment. It contains seven
      amyloidogenic determinants. Circular dichroism analysis and fluorescence
      spectroscopy with thioflavin T indicate the presence of beta-sheet structures in
      Bgl2p isolates. Bgl2p forms fibrils, a process that is enforced in the presence
      of other cell wall components. Thus the data obtained is the first evidence for
      amyloid-like properties of yeast cell wall protein-glucantransferase Bgl2p.

PMID- 19098440
TI  - Left handed beta helix models for mammalian prion fibrils.
AB  - We propose models for in vitro grown mammalian prion protein fibrils based upon
      left handed beta helices formed both from the N-terminal and C-terminal regions
      of the proteinase resistant infectious prion core. The C-terminal threading onto
      a beta-helical structure is almost uniquely determined by fixing the cysteine
      disulfide bond on a helix corner. In comparison to known left handed helical
      peptides, the resulting model structures have similar stability attributes
      including relatively low root mean square deviations in all atom molecular
      dynamics, substantial side-chain-to-side-chain hydrogen bonding, good volume
      packing fraction, and low hydrophilic/hydrophobic frustration. For the N
      terminus, we propose a new threading of slightly more than two turns, which
      improves upon the above characteristics relative to existing three turn beta
      helical models. The N-terminal and C-terminal beta helices can be assembled into
      eight candidate models for the fibril repeat units, held together by large hinge
      (order 30 residues) domain swapping, with three amenable to fibril promoting
      domain swapping via a small (five residue) hinge on the N-terminal side. Small
      concentrations of the metastable C-terminal beta helix in vivo might play a
      significant role in templating the infectious conformation and in enhancing
      conversion kinetics for inherited forms of the disease and explain resistance
      (for canines) involving hypothesized coupling to the methionine 129 sulfur known
      to play a role in human disease.

PMID- 19098441
TI  - Anti-bovine prion protein RNA aptamer containing tandem GGA repeat interacts both
      with recombinant bovine prion protein and its beta isoform with high affinity.
AB  - In order to obtain RNA aptamers against bovine prion protein (bPrP), we carried
      out in vitro selection from RNA pools containing a 55-nucleotide randomized
      region to target recombinant bPrP. Most of obtained aptamers contained conserved
      GGA tandem repeats (GGA)(4) and aptamer #1 (apt #1) showed a high affinity for
      both bPrP and its beta isoform (bPrP-beta). The sequence of apt #1 suggested that
      it would have a G-quadruplex structure, which was confirmed using CD spectra in
      titration with KCl. A mutagenic study of this conserved region, and competitive
      assays, showed that the conserved (GGA)(4) sequence is important for specific
      binding to bPrP and bPrP-beta. Following 5'-biotinylation, aptamer #1
      specifically detected PrP(c) in bovine brain homogenate in a Northwestern
      blotting assay. Protein deletion mutant analysis showed that the bPrP aptamer
      binds within 25-131 of the bPrP sequence. Interestingly, the minimized aptamer #1
      (17 nt) showed greater binding to bPrP and bPrP-beta as compared to apt #1. This
      minimized form of aptamer #1 may therefore be useful in the detection of bPrP,
      diagnosis of prion disease, enrichment of bPr and ultimately in gaining a better
      understanding of prion diseases.

PMID- 19098442
TI  - Prion interference with multiple prion isolates.
AB  - Co-inoculation of prion strains into the same host can result in interference,
      where replication of one strain hinders the ability of another strain to cause
      disease. The drowsy (DY) strain of hamster-adapted transmissible mink
      encephalopathy (TME) extends the incubation period or completely blocks the hyper
      (HY) strain of TME following intracerebral, intraperitoneal or sciatic nerve
      routes of inoculation. However, it is not known if the interfering effect of the
      DY TME agent is exclusive to the HY TME agent by these experimental routes of
      infection. To address this issue, we show that the DY TME agent can block hamster
      adapted chronic wasting disease (HaCWD) and the 263K scrapie agent from causing
      disease following sciatic nerve inoculation. Additionally, per os inoculation of
      DY TME agent slightly extends the incubation period of per os superinfected HY
      TME agent. These studies suggest that prion strain interference can occur by a
      natural route of infection and may be a more generalized phenomenon of prion
      strains.

PMID- 19098443
TI  - Insights into intragenic and extragenic effectors of prion propagation using
      chimeric prion proteins.
AB  - The study of fungal prion proteins affords remarkable opportunities to elucidate
      both intragenic and extragenic effectors of prion propagation. The yeast prion
      protein Sup35 and the self-perpetuating [PSI+] prion state is one of the best
      characterized fungal prions. While there is little sequence homology among known
      prion proteins, one region of striking similarity exists between Sup35p and the
      mammalian prion protein PrP. This region is comprised of roughly five octapeptide
      repeats of similar composition. The expansion of the repeat region in PrP is
      associated with inherited prion diseases. In order to learn more about the
      effects of PrP repeat expansions on the structural properties of a protein that
      undergoes a similar transition to a self-perpetuating aggregate, we generated
      chimeric Sup35-PrP proteins. Using both in vivo and in vitro systems we described
      the effect of repeat length on protein misfolding, aggregation, amyloid formation
      and amyloid stability. We found that repeat expansions in the chimeric prion
      proteins increase the propensity to initiate prion propagation and enhance the
      formation of amyloid fibers without significantly altering fiber stability.

PMID- 19098444
TI  - Curli provide the template for understanding controlled amyloid propagation.
AB  - The uncontrolled formation of amyloid fibers is the hallmark of more than twenty
      human diseases. In contrast to disease-associated amyloids, which are the
      products of protein misfolding, E. coli assembles functional amyloid fibers
      called curli on its surface using an elegant biogenesis machine. Composed of a
      major subunit, CsgA, and a minor subunit, CsgB, curli play important roles in
      host cell adhesion, long-term survival and other bacterial community behaviors.
      Assembly of curli fibers is a template-directed conversion process where membrane
      tethered CsgB initiates CsgA polymerization. The CsgA amyloid core is composed of
      five imperfect repeating units. In a series of in vivo and in vitro experiments,
      we determined the sequence and structural determinants that guide the initiation
      and propagation of CsgA polymers. The CsgA N- and C-terminal repeating units
      govern its polymerization and responsiveness to CsgB. Specifically, conserved
      glutamine and asparagine residues present in the CsgA N- and C-terminal repeating
      units are required for CsgB-mediated nucleation and efficient self-assembly.

PMID- 19098445
TI  - The irreversible binding of amyloid peptide substrates to insulin-degrading
      enzyme: a biological perspective.
AB  - Insulin-degrading enzyme (IDE) is a conserved Zn(2+)metalloendopeptidase involved
      in insulin degradation and in the maintenance of brain steady-state levels of
      amyloid beta peptide (Abeta) of Alzheimer's disease (AD). Our recent
      demonstration that IDE and Abeta are capable of forming a stoichiometric and
      extremely stable complex raises several intriguing possibilities regarding the
      role of this unique protein-peptide interaction in physiological and pathological
      conditions. These include a protective cellular function of IDE as a "dead-end
      chaperone" alternative to its proteolytic activity and the potential impact of
      the irreversible binding of Abeta to IDE upon its role as a varicella zoster
      virus receptor. In a pathological context, the implications for insulin signaling
      and its relationship to AD pathogenesis are discussed. Moreover, our findings
      warrant further research regarding a possible general and novel interaction
      between amyloidogenic peptides and other Zn(2+)metallopeptidases with an IDE-like
      fold and a substrate conformation-dependent recognition mechanism.

PMID- 19098446
TI  - ATRA and KL promote differentiation toward the meiotic program of male germ
      cells.
AB  - While it is known that retinoic acid (RA) induces meiosis in mouse female fetal
      gonads, the mechanisms which regulate this process during spermatogenesis are
      poorly understood. We show that the All trans RA derivative (ATRA) and Kit Ligand
      (KL) increase meiotic entry of postnatal mouse spermatogonia in vitro without
      synergism. Competence to enter meiosis is reached by spermatogonia only at the
      stage in which they undergo Kit-dependent divisions. Besides increasing Kit
      expression in spermatogonia, ATRA also upregulates KL expression in Sertoli
      cells. Both ATRA and KL increase the expression of Stimulated by Retinoic Acid
      Gene 8 and Dmc1, an early meiotic marker. A specific Kit tyrosine kinase
      inhibitor prevents the increase in the number of meiotic cells induced by both
      the two factors, suggesting that they converge on common Kit-dependent signalling
      pathways. Meiotic entry induced by ATRA and KL is independent from their ability
      to affect germ cell viability, and is mediated by the activation of PI3K and MAPK
      pathways through Kit autophosphorylation. ATRA-induced phosphorylation of the two
      downstream kinases is mediated by a non-genomic mechanism. These data suggest
      that RA may control the timing of meiosis by influencing both the somatic and the
      germ cell compartment of the postnatal testis through the activation of the
      KL/Kit system.

PMID- 19098447
TI  - Safingol (L-threo-sphinganine) induces autophagy in solid tumor cells through
      inhibition of PKC and the PI3-kinase pathway.
AB  - Safingol, the synthetic L-threo-stereoisomer of endogenous (D-erythro-)
      sphinganine, is an inhibitor of protein kinase C and sphingosine kinase in vitro,
      and in some cell types has been implicated in ceramide generation and induction
      of apoptosis. Utilizing electron microscopy, acridine orange staining, and
      immunoblot and fluorescent localization studies of the myosin light chain
      associated protein (LC3), we determined that safingol induces cell death of an
      exclusively autophagic character and lacking any of the hallmarks of apoptosis.
      Safingol inhibited PKCbeta-I, PKC delta and PKC epsilon, and inhibited
      phosphorylation of critical components of the PI3k/Akt/mTOR pathway (Akt, p70S6k
      and rS6) and the MAPk pathway (ERK). Inhibition of PI3k with LY294002 or
      suppression of PKC delta and PKC epsilon with siRNA in HCT-116 cells induced
      autophagy, though not to the extent caused by safingol. Conversely, activation of
      PKCs with phorbol 12,13-dibutyrate (PDBu) or transient transfection of a
      constitutively active form of Akt each reduced safingol's autophagic induction,
      but not completely, indicating that Akt- and PKC-dependent pathways both
      contribute partially and independently to safingol-induced autophagy.
      Accordingly, combining siRNA depletion of PKC epsilon with LY294002 inhibition of
      PI3k induced autophagy to a degree comparable to safingol. Liquid chromatography,
      electrospray tandem mass spectrometry analysis indicated that safingol did not
      elevate levels of any endogenous sphingolipids previously shown to induce
      autophagy (ceramide, sphingosine-1-phosphate and dihydroceramide); therefore,
      these effects may be due to safingol per se or another metabolite. Thus, our
      studies establish that safingol induces autophagy through inhibition of PKCs and
      PI3k by safingol directly rather than via changes in endogenous sphingolipids.

PMID- 19098448
TI  - Promoter methylation of HIN-1 in the progression to esophageal squamous cancer.
AB  - HIN-1 (High in normal-1) is a tumor suppressor gene that is highly expressed in
      many epithelial tissues, including breast lung, trachea, pancreas, prostrate and
      salivary gland. Inactivation of HIN-1 expression by promoter methylation is
      frequent in many epithelial carcinomas and carcinoma-in-situ, including breast,
      lung and nasopharyngeal. Because HIN-1 silencing commences at an early stage of
      malignant transformation in these tissues, it may be a useful marker for tumor
      presence. The status of HIN-1 regulation in esophageal cancer has not been
      previously reported. Thus, we analyzed 18 esophageal cancer cell lines for HIN-1
      expression and methylation by reverse transcription PCR (RT-PCR) and methylation
      specific PCR (MSP). HIN-1 gene silencing and promoter methylation was present in
      13 (72%) of the cell lines. Bisulfite-treated sequencing confirmed the
      methylation status in cell lines and demonstrated dense methylation of HIN-1
      throughout the promoter region. Epigenetic changes of HIN-1 were examined
      throughout the progression of carcinogenesis in esophageal squamous lesions
      through analysis of archived surgical specimens from patients with normal
      esophageal mucosa (n = 17), grade I dysplasia (n = 39), grade II dysplasia (n =
      12), grade III dysplasia (n = 9), and invasive squamous esophageal cancer (n =
      126). Methylation of HIN-1 was present in 0% of normal mucosa, 31% of grade I
      dysplasia, 33% of grade II dysplasia, 44% of grade III dysplasia, and 50% of
      esophageal cancer specimens analyzed. These studies demonstrate HIN-1 silencing
      is associated with dense promoter region hypermethylation in esophageal cancer
      and suggest that methylation of HIN-1 is an early event in dysplastic
      transformation.

PMID- 19098449
TI  - Epigenetics meets next-generation sequencing.
AB  - Next-generation sequencing is poised to unleash dramatic changes in every area of
      molecular biology. In the past few years, chromatin immunoprecipitation (ChIP) on
      tiled microarrays (ChIP-chip) has been an important tool for genome-wide mapping
      of DNA-binding proteins or histone modifications. Now, ChIP followed by direct
      sequencing of DNA fragments (ChIP-seq) offers superior data with less noise and
      higher resolution and is likely to replace ChIP-chip in the near future. We will
      describe advantages of this new technology and outline some of the issues in
      dealing with the data. ChIP-seq generates considerably larger quantities of data
      and the most challenging aspect for investigators will be computational and
      statistical analysis necessary to uncover biological insights hidden in the data.

PMID- 19098450
TI  - Cancer gene silencing without DNA hypermethylation.
AB  - Both DNA hypermethylation and Polycomb-mediated histone methylation induce gene
      silencing in cancer, but largely in two separate paths. Hence, different
      pharmacologic approaches are required to reactivate genes silenced by distinct
      epigenetic mechanisms.

PMID- 19098451
TI  - Folic acid and sodium butyrate prevent tumorigenesis in a mouse model of
      colorectal cancer.
AB  - Colorectal cancer is a leading cause of morbidity and mortality worldwide, and
      its incidence has been increasing in recent years. The role of epigenetic
      modifications, including DNA methylation and histone modifications, has only
      recently been investigated. In this study, the effects of epigenetic agents such
      as folic acid (FA) and sodium butyrate (NaBu) on the development of colorectal
      cancer induced by 1,2-dimethylhydrazine (DMH) using ICR mice was examined. Of the
      mice treated in a chemopreventive manner with epigenetic agents, FA and NaBu, 15
      50% developed colorectal cancer at 24 weeks compared with a 95% incidence of
      colorectal cancer in DMH-treated control mice. Folate deficiency can alter
      cytosine methylation in DNA leading to inappropriate activation of the proto
      oncogene c-myc. We detected lower levels of p21(WAF1) gene expression in
      colorectal cancer samples, as well as significantly lower levels of acetylated
      histone H3, compared with samples from corresponding normal colorectal mucosa. In
      contrast, administration of NaBu increased levels of p21(WAF1) mRNA and p21(WAF1)
      protein, and was associated with an accumulation of histone acetylation. In
      summary, our results show that FA and NaBu reduce the incidence of colorectal
      cancer induced by DMH-induced in ICR mice, and therefore we hypothesize that
      targeting epigenetic targets should be further investigated for the prevention of
      colorectal cancer in humans.

PMID- 19098452
TI  - Ankyrin-based targeting pathway regulates human sinoatrial node automaticity.
AB  - Cellular defects in ankyrin-based ion channels and transporter targeting pathways
      have previously been linked with abnormal vertebrate physiology and human
      disease. In a recent study, our group linked dysfunction in cardiac ankyrin-B
      function with human sinus node disease. Ankyrin-B deficient mice displayed
      bradycardia and heart rate variability similar to individuals harboring an ANK2
      variant. Isolated sinoatrial node (SAN) cells from ankyrin-B-deficient animals
      displayed abnormal membrane expression of Na+/Ca2+ exchanger (NCX1), Na+/K+
      ATPase (NKA), IP3 receptor (IP3R) and, surprisingly, Ca(V)1.3. Loss of ankyrin-B
      promoted slow and irregular Ca2+ release, as well as afterdepolarizations in
      isolated SAN cardiomyocytes. Our findings suggest that ankyrin-B serves as a
      critical focal point for channels and transporters important for sarcoplasmic
      reticulum (SR) calcium homeostasis as well as membrane depolarization in SAN
      cells. The severity and penetrance of human ANK2 sinus node dysfunction likely
      reflects the essential role of ankyrin-B for orchestrating membrane function of
      multiple SAN ion channel and transporters within a single functional pathway.
      Therefore, ankyrin-based pathways may serve as ideal therapeutic targets in SAN
      cardiomyocytes where a "multi-hit" approach is necessary to impact a complex
      process such as SAN cell automaticity. In summary, our new findings define a
      novel genetic basis for human SND and expand our understanding of the critical
      role that ankyrin-based targeting pathways play in excitable cell physiology.

PMID- 19098453
TI  - BRCA1 mutations contribute to cell  motility and invasion by affecting  its main
      regulators.

PMID- 19098455
TI  - RNA research in the rustbelt.
AB  - Deep in the heart of Ohio, scientists from across the Midwest gathered in October
      to share their latest findings and highlight the strength of RNA research in the
      heartland. Represented were researchers from Delaware, Indiana, Kentucky,
      Michigan, Ohio, Pennsylvania and West Virginia. With over 220 participants, the
      2008 annual Rustbelt RNA Meeting (RRM) was the largest gathering of this group in
      its 10-year history. The success of this year's RRM lies on the extraordinary
      efforts of organizers Dawn Chandler (Ohio State University) and Girish Shukla
      (Cleveland State University).

PMID- 19098454
TI  - Deconstructing feedback-signaling networks to improve anticancer therapy with
      mTORC1 inhibitors.
AB  - Targeting mTOR complex 1 (mTORC1), which regulates general protein translation,
      represents one of the most attractive approaches to treating cancer, since
      upregulation of this pathway is a common hallmark in many tumors. Nevertheless,
      the use of rapamycin and its analogs in the clinic has revealed that mTORC1
      pathway is embedded in a network of signaling cross-talks and feedbacks which
      might reduce its effectiveness in cancer. We have recently described a novel
      signaling feedback stemming from mTORC1 inhibition, which leads to the activation
      of ERK-MAPK (MAPK) pathway. The observation that MAPK is activated by rapamycin
      and its analogs in vitro, in mouse models, and cancer patient biopsies sets the
      rationale for the combined use of MAPK and mTORC1 inhibitors in cancer therapy.
      In this extra-view, we integrate our findings into the mTORC1 signaling network
      and discuss its relevance for the design of combinatorial therapies with mTORC1
      inhibitors.

PMID- 19098456
TI  - Osteosarcoma: Conventional treatment vs. gene therapy.
AB  - Osteosarcoma (OS) remains the most common primary malignant bone cancer affecting
      children and adolescents. Majority of patients are subjected to surgery and
      chemotherapy with limited alternatives to consider. However, with increasing
      knowledge of the molecular pathogenesis of OS, advancements in OS therapy
      research fields have developed potential agents for a more targeted and localised
      approach to treatment. Thus, this review attempts to examine some common
      treatment strategies (surgery, radiotherapy and chemotherapy) employed clinically
      as well as recent developments in newer experimental therapy methods (gene
      therapy) which might potentially benefit patients.

PMID- 19098457
TI  - The biochemistry of RNA metabolism studied in situ.
AB  - In vitro assays have contributed important insights into the mechanisms of RNA
      metabolism in cells. A growing collection of microscopy techniques is allowing
      the measurement of macromolecular binding and complex formation in the context of
      a real cell. We will first discuss two of the more established techniques.
      Fluorescence resonance energy transfer (FRET) identifies binding partners, pairs
      of molecules residing in the same macromolecular complexes. The complimentary
      technique of fluorescence recovery after photobleaching (FRAP) measures the rates
      of binding and unbinding of those molecules in their complexes. A newer technique
      -in vitro FRAP--assesses the regulation of binding and complex formation by co
      factors in the nucleus.

PMID- 19098458
TI  - RNA-binding specificity of Y-box protein 1.
AB  - Y-box protein 1 (YB-1) is a multifunctional DNA/RNA-binding protein that
      regulates transcription and translation. The specificity of YB-1's RNA binding
      and its consequences are unknown. Because expression and subcellular localization
      of YB-1 have been reported to be important in breast cancer, we determined the
      specificity and functional impact of YB-1 mRNA-binding in MCF7 breast cancer
      cells. We used YB-1 antibodies to immunoprecipitate YB-1 and microarray profiling
      to compare YB-1-bound and total poly(A) RNA. We demonstrated that YB-1 mRNA
      binding was preferential. Transcript sequences significantly associated with this
      binding had high GC content. Selected YB-1 mRNA-binding targets were confirmed by
      QRT-PCR. However, downregulation of YB-1 levels by siRNA did not affect their RNA
      or protein expression. Thus, YB-1 has RNA-binding specificity; however, YB-1
      binding does not necessarily regulate the stability or translation of its mRNA
      targets. Further study is needed to determine the functional consequences of
      selective YB-1 mRNA binding.

PMID- 19098460
TI  - Denervation-induced oxidative stress and autophagy signaling in muscle.
AB  - Alterations in contractile activity influence the intracellular homeostasis of
      muscle, which results in adaptations in the performance and the phenotype of this
      tissue. Denervation is an effective disuse model that functions to change the
      intracellular environment of muscle leading to a rapid loss in mass, a decrease
      in mitochondrial content, and an elevation in both proapoptotic protein
      expression and myonuclear apoptosis. Recent investigations have shown that
      alternative degradation pathways such as autophagy are activated in conjunction
      with apoptosis during chronic muscle disuse. We have previously shown that seven
      days of muscle disuse increases the expression of Beclin 1. Furthermore, we have
      also detected a significant increase in the expression of LC3-II, a known
      component of autophagy. In addition to its upregulation, denervation appears to
      induce the translocation of LC3-II to mitochondrial membranes. Collectively,
      these increases in protein expression suggest that autophagy signaling is
      upregulated in response to denervation, and that these pathways may
      preferentially target mitochondria for degradation in skeletal muscle.

PMID- 19098459
TI  - Macroautophagy: the key ingredient to a healthy diet?
AB  - Dietary compounds can influence the risk of cancer and other diseases through
      diverse mechanisms which include the activation or inhibition of macroautophagy.
      Macroautophagy is a catabolic process for the lysosomal degradation and recycling
      of cytoplasmic constituents which has been implicated in several pathologies,
      including cancer and neurodegeneration. In some instances, macroautophagy acts to
      suppress tumor formation and neural degeneration. Thus, it may be feasible to
      design diets, supplements or therapeutics that can alter the level of
      macroautophagy within cells to prevent or treat disease. While critical questions
      still need to be answered before we can safely and effectively implement such a
      strategy, we provide here a review of the literature regarding dietary
      constituents that have a demonstrated macroautophagy-modulating function.

PMID- 19098461
TI  - Regulation of HMGB1 release by autophagy.
AB  - The characteristics of tumor cell killing by an anticancer agent can determine
      the long-term effectiveness of the treatment. For example, if dying tumor cells
      release the immune modulator HMGB1 after treatment with anticancer drugs, they
      can activate a tumor-specific immune response that boosts the effectiveness of
      the initial treatment. Recent work from our group examined the mechanism of
      action of a targeted toxin called DT-EGF that selectively kills Epidermal Growth
      Factor Receptor-expressing tumor cells. We found that DT-EGF kills glioblastoma
      cells by a caspase-independent mechanism that involves high levels of autophagy,
      which inhibits cell death by blocking apoptosis. In contrast, DT-EGF kills
      epithelial tumor cells by caspase-dependent apoptosis and in these cells
      autophagy is not induced. These differences allowed us to discover that the
      different death mechanisms were associated with differences in the release of
      HMGB1 and that autophagy induction is required and sufficient to cause release of
      HMGB1 from the dying cells. These data identify a new function for autophagy
      during cell death and open up the possibility of manipulating autophagy during
      cancer treatment as a way to influence the immunogenicity of dying tumor cells.

PMID- 19098462
TI  - What do natural antisense transcripts regulate?
AB  - In human and mouse up to 72% of all genomic loci show evidence of transcription
      from both sense and antisense strands. The benefit of the resulting natural
      antisense transcripts (NATs) remains unclear, largely because of a lack of
      significant correlation between gene ontology and antisense transcription. Here
      we suggest that a well defined group of NATs may be identified based on
      structural characteristics. Specifically, these NATs are processed transcripts
      that are complementary to the corresponding processed sense transcripts in exonic
      regions. Recent reports have established that co-expressed sense transcripts/NATs
      are processed into short RNAs. These so called endo-siRNAs are found in both
      sense and antisense orientation and were hypothesized to mediate pseudogene
      silencing. Here we propose that NATs are biologically important sources of endo
      siRNAs. We also propose that endo-siRNAs are essential components of a regulatory
      network to control the mutagenic burden that unfolds on nucleic acid level
      without direct consequences on protein expression.

PMID- 19098463
TI  - Low-grade endometrial adenocarcinoma: a diagnostic algorithm for distinguishing
      atypical endometrial hyperplasia and other benign (and malignant) mimics.
AB  - The distinction between endometrial hyperplasia and well-differentiated
      adenocarcinoma of the endometrium continues to be a difficult differential
      diagnosis in surgical pathology. Evidence-based diagnostic criteria for well
      differentiated endometrial adenocarcinoma focus on histologic features that
      predict myoinvasion in the hysterectomy specimen. Only 2 diagnostic criteria with
      significant power aid in this distinction: complex glandular architectural
      patterns (glandular confluence, intraglandular complexity, and hierarchical
      papillary architecture) and marked cytologic atypia beyond that typically defined
      as atypical hyperplasia (ie, prominent macronucleoli visible at low power and
      marked nuclear pleomorphism). Application of these 2 criteria in problematic
      endometrial proliferations allows stratification of patients into 3 risk
      categories: very low risk (< 0.05% risk of myoinvasion at hysterectomy)=complex
      atypical hyperplasia; intermediate risk (5.5% risk of myoinvasion at
      hysterectomy)=complex atypical hyperplasia, cannot exclude well-differentiated
      adenocarcinoma (borderline); and high risk (20% risk of myoinvasion at
      hysterectomy)=well-differentiated adenocarcinoma. In order to optimize the use of
      these diagnostic criteria, a variety of gland forming lesions that may mimic well
      differentiated endometrioid adenocarcinoma must first be excluded. In addition,
      unusual morphologic patterns of low-grade endometrioid adenocarcinoma should be
      recognized, as they may cause confusion with other, higher grade (and therefore,
      more clinically aggressive) endometrial processes.

PMID- 19098464
TI  - Molecular alterations in hereditary and sporadic thyroid and parathyroid
      diseases.
AB  - Thyroid and parathyroid diseases are fairly common and can be either hereditary
      or sporadic in nature. Tumors and tumor-like processes account for the majority
      of surgical pathology specimens in both of these endocrine organs. Molecular
      alterations are well known to occur in both the hereditary and the sporadic
      settings, and include alterations in tumor suppressor genes and oncogenes. The
      genetic pathways of tumors of parathyroid and thyroid are beginning to be well
      understood and are proving to be useful diagnostic, prognostic, and potential
      therapeutic targets. The molecular alterations in parathyroid and thyroid tumors
      and tumor-like processes are reviewed, with a focus on the potentially clinically
      useful diagnostic markers.

PMID- 19098465
TI  - The expanding family of glioneuronal tumors.
AB  - Three new entities have been recently added to the group of glioneuronal tumors
      in the most recent update of the World Health Organization classification of
      tumors of the central nervous system: papillary glioneuronal tumor, rosetted
      glioneuronal tumor with neuropil-like islands, and rosette-forming glioneuronal
      tumor of the fourth ventricle. These tumors are relatively infrequent lesions,
      and because of that, they can be challenging to diagnose for the practicing
      pathologist. In this article, we summarize the clinical and pathologic findings
      of these new lesions.

PMID- 19098466
TI  - Epstein-Barr virus in lymphoproliferative processes: an update for the diagnostic
      pathologist.
AB  - The Epstein-Barr virus is an orally transmitted herpesvirus that is widespread in
      human populations and exhibits marked B-cell tropism. It is associated with more
      human neoplasms than any other known virus, and its role in the pathogenesis of
      such neoplasms has been the subject of intense investigation. This review
      presents an overview and update of the biology of Epstein-Barr virus and the
      diagnostic features of lymphoproliferative disorders associated with this
      intriguing human pathogen.

PMID- 19098467
TI  - Lupus mastitis: a clinicopathologic review and addition of a case.
AB  - Lupus mastitis (LM) is a rare presentation of lupus erythematosus profundus or
      lupus panniculitis, an unusual and rare clinical variant of lupus erythematosus
      itself in which the inflammatory reaction occurs primarily in the deep
      subcutaneous adipose. Although not required for diagnosis, essentially all cases
      of LM present with systemic or discoid lupus. The etiology is uncertain.
      Histologically it is defined by a lymphocytic lobular panniculitis and a
      characteristic hyaline sclerosis of the adipose tissue. Treatment is primarily
      medical due to exacerbation of disease by surgical intervention. A high index of
      suspicion, and familiarity of the histologic findings, is therefore required to
      make an accurate diagnosis and prevent further unwarranted diagnostic procedures.
      Herein, we provide a literature-based review of the clinical, radiologic, and
      pathologic findings of LM and its treatment and prognosis with the addition of a
      case for the literature.

PMID- 19098468
TI  - D2-40 immunohistochemistry--so far!
AB  - D2-40 is a commercially available monoclonal antibody directed against human
      podoplanin, a transmembrane mucoprotein that is expressed in lymphatic
      endothelial cells. Since its introduction, D2-40 immunoexpression has been
      described in a variety of lymphovascular neoplasms including lymphangioma, Kaposi
      sarcoma, and hemangioendothelioma, as well as nonvascular neoplasms such as
      epithelioid mesothelioma, seminoma, and hemangioblastoma. More recently, D2-40
      immunoexpression has been reported in primary adrenal cortical tumors,
      schwannomas, and adnexal tumors of the skin. This brief review provides an update
      on the ever-expanding proposed applications of D2-40 immunohistochemistry in
      surgical pathology.

PMID- 19098469
TI  - Evaluation design for large-scale HIV prevention programmes: the case of Avahan,
      the India AIDS initiative.
AB  - BACKGROUND: Closing the HIV prevention gap to prevent HIV infections requires
      rapid, worldwide rollout of large-scale national programmes. Evaluating such
      programmes is challenging and complex, requiring clarity of evaluation purpose
      and evidential approaches substantively different to those employed for pilots
      and small programmes. OBJECTIVES: This paper describes the evaluation design for
      the implementation phase of Avahan, the India AIDS initiative, a large HIV
      prevention programme funded by the Bill and Melinda Gates Foundation. Avahan,
      which began in December 2003, has a 10-year charter to impact the Indian epidemic
      and its response by implementing an HIV prevention programme targeting core and
      bridge groups in 83 districts of six Indian states, transferring the programme to
      the Government of India, and disseminating programme learning. METHODS: The
      foundation commissioned an external process to design Avahan's evaluation
      framework. An independent advisory group oversees and guides course corrections
      in the execution of this framework. RESULTS: Avahan's evaluation framework
      comprises: trend and synthetic analysis of data from core, bridge and household
      biobehavioural surveys in a subset of intervention districts, denominator
      estimates and programme monitoring from all intervention districts, and
      government's antenatal surveillance (two sites per district in all districts);
      bespoke transmission dynamics modelling to estimate infections averted (subset of
      districts); cost effectiveness studies (subset of districts). In addition, there
      are other knowledge-building and quality-monitoring activities. CONCLUSION:
      Rather than a small set of monofocal outcome measures, scaled programmes require
      nuanced evaluations that approximate programmatic scale by collecting data with
      different levels of geographical scope, synthesize multiple data and methods to
      arrive at a composite picture, and can cope with continuous environmental and
      programme evolution.

PMID- 19098470
TI  - Impact of an intensive HIV prevention programme for female sex workers on HIV
      prevalence among antenatal clinic attenders in Karnataka state, south India: an
      ecological analysis.
AB  - OBJECTIVES: To examine the impact of an intensive HIV preventive intervention
      (IPI) among female sex workers (FSW) on community HIV transmission, as
      represented by HIV prevalence among young antenatal clinic (ANC) attenders in
      Karnataka state, south India. METHODS: The IPI was initiated in 18 of the 27
      districts in Karnataka in 2003, and was generally at scale by mid-2005, covering
      over 80% of the urban FSW population. We examined trends over time in HIV
      prevalence from annual HIV surveillance conducted among ANC attenders in
      Karnataka under the age of 25 years from 2003 to 2007, comparing the IPI with the
      other districts. RESULTS: Overall, HIV prevalence among ANC attenders under 25
      years of age declined from 1.40% to 0.77%. In a multivariate model, the decline
      in HIV prevalence in the IPI districts compared to the other districts was
      statistically significant (P = 0.01), with an adjusted annual odds ratio of 0.88
      (95% CI 0.79-0.97). The decline in standardized HIV prevalence in the IPI
      districts over the period was 56%, compared to 5% in the non-IPI districts.
      CONCLUSIONS: Although this analysis is limited by lack of precise comparative
      data on intervention coverage and intensity, it supports the notion that scaled
      up, intensive, targeted HIV preventive interventions among high-risk groups can
      have a measurable and relatively rapid impact on HIV transmission in the general
      population, particularly young sexually active populations as represented by ANC
      attenders. Such focused intervention programmes should be rapidly taken to scale
      in all HIV epidemics, and especially in concentrated epidemics such as in India.

PMID- 19098471
TI  - Power, community mobilization, and condom use practices among female sex workers
      in Andhra Pradesh, India.
AB  - OBJECTIVES: We used a structural interventions framework to analyse the
      associations between power and condom use among a sample of female sex workers
      (FSW), and how exposure to a local community mobilization intervention (CMI)
      affects these associations. DESIGN: Data came from a cross-sectional survey of
      812 FSW in the East Godavari district of Andhra Pradesh, India, recruited through
      respondent-driven sampling. METHODS: We identified three types of power -
      collective power, control over work, and economic power, and three dimensions of
      collective power - collective identity, efficacy, and agency. Multivariate
      logistic regression analysis was used to analyse the relationship of these three
      types of power and exposure to a CMI with consistent condom use with clients.
      RESULTS: A total of 803 respondents exchanged sex with an occasional or regular
      client in the 7 days before the interview. Multivariate logistic regression shows
      that control over both the type of sex [adjusted odds ratio (AOR) 1.70, 95%
      confidence interval (CI) 1.23-2.34] and the amount charged (AOR 1.56, 95% CI 1.12
      2.16), and economic dependence (AOR 0.54, 95% CI 0.35-0.83) are associated with
      consistent condom use as is programme exposure (AOR 2.09, 95% CI 1.48-2.94). The
      interaction between programme exposure and collective agency was also significant
      (chi-square 6.62, P = 0.01). Among respondents who reported both programme
      exposure and high levels of collective agency, the odds ratio of consistent
      condom use was 2.5 times that of other FSW. CONCLUSION: A structural
      interventions framework is useful for understanding HIV risk among FSW. More
      needs to be done to promote FSW control over work and access to economic
      resources.

PMID- 19098472
TI  - Prevalence and determinants of HIV and sexually transmitted infections in a
      general population-based sample in Mysore district, Karnataka state, southern
      India.
AB  - OBJECTIVES: To estimate HIV and sexually transmitted infection (STI) prevalence
      within the general population of Mysore district, and to examine differences in
      the distribution of risk factors associated with HIV prevalence stratified by
      sex. METHODS: A community-based study was conducted in Mysore, Karnataka state,
      southern India, between October 2005 and November 2006; final sample size 4653. A
      face-to-face interview was conducted, and blood and urine specimens collected to
      measure HIV and STI prevalences. Risk factors for HIV among men and women were
      examined using weighted and clustered logistic regression. RESULTS: Weighted HIV
      prevalence was 0.8% [95% confidence interval (CI) 0.52-1.09] overall and 0.7%
      (0.35-1.08) and 0.9% (0.51-1.37) in rural and urban populations, respectively.
      The prevalence of syphilis, gonorrhoea and chlamydial infection was 2.8% for men
      and 1.8% for women. In multivariate analysis, higher HIV prevalence was
      associated with ever having used a condom [odds ratio (OR) 2.75, 95% CI 1.01
      7.47] and number of lifetime partners for men (OR 6.9, 95% CI 2.18-21.91). For
      women, HIV infection was associated with condom use at last sexual intercourse
      (OR 10.51, 95% CI 2.05-53.79), number of lifetime partners and reporting 'don't
      know' for whether ever had anal sex (OR 9.10, 95% CI 1.14-72.34). CONCLUSIONS:
      HIV prevalence in the general population of Mysore was found to be comparable to
      recent prevalence estimates for Karnataka state, and also similar to recent
      prevalence estimates from antenatal clinic attenders for the district. Few
      modifiable risk factors for HIV infection were identified. There is evidence from
      this study that high-risk behaviour may have been underreported, but the
      prevalence of STI was generally low.

PMID- 19098473
TI  - HIV risk behaviours among contracted and non-contracted male migrant workers in
      India: potential role of labour contractors and contractual systems in HIV
      prevention.
AB  - OBJECTIVE(S): To assess the HIV risk behaviours of male migrant contracted and
      non-contracted labourers in India and to understand the role of contract labour
      systems for use in HIV prevention efforts. METHODS: Cross-sectional surveys (N =
      11 219) were conducted with male migrant workers, aged 18-49 years from 21
      districts in four high HIV prevalence states of India. Analyses involved data
      from the subsample of contracted labour (n = 3880; 35% of total sample) to assess
      the prevalence of HIV risk behaviours and sexually transmitted infection (STI)
      symptoms and further comparisons with non-contracted labourers. RESULTS:
      Contracted male labourers are largely young; 70% were between the ages of 18 and
      29 years. Over half (55%) were married, and a third (34%) resided away from their
      wives because of migrant work. More than one in six contract labourers (17%)
      reported having sex with a sex worker, and two-fifths of these reported an
      inconsistent use of condoms. One in 10 reported sex with both sex workers and non
      spousal unpaid female partners in the past year in the places they had migrated
      to, and 31% reported sex with either a sex worker or non-spousal unpaid female
      partner in their places of origin over the past 2 years. After adjustment for
      sociodemographic characteristics, the contracted labourers were significantly
      more likely to report alcohol use and HIV risk behaviours than non-contracted
      labourers. CONCLUSION: The existence of a wide network of labour contractors and
      a structured infrastructure of the contract system provides opportunities for
      effective and sustained worksite HIV prevention programmes among contracted male
      migrant workers in India.

PMID- 19098475
TI  - Using mathematical modelling to investigate the plausibility of attributing
      observed antenatal clinic declines to a female sex worker intervention in
      Karnataka state, India.
AB  - OBJECTIVES: To determine whether the 32% and 52% decline in ANC HIV prevalence
      among female antenatal clinic (ANC) attenders, observed in Avahan districts
      between 2004 and 2006, and 2007 respectively, in the state of Karnataka could be
      due to a HIV preventive intervention targeted at female sex workers and their
      clients. METHODS: An exhaustive sensitivity analysis, based on an age and parity
      structured mathematical model of HIV transmission in a general and ANC
      population, was undertaken to estimate intervention impact in different
      concentrated HIV epidemics representative of those in Karnataka districts. To
      assess if the large reduction in ANC HIV prevalence could be solely due to the
      intervention, we simulated a very optimistic intervention. RESULTS: If 100% of
      FSWs were reached and condom use between clients and FSWs increased
      instantaneously to over 80% of sex acts, the expected intervention decline (50th,
      (10th, 90th) percentiles) among the overall and 15-19 year old ANC population
      after three years of intense intervention activity was 21% (14%, 27%) and 27%
      (19%, 35%); with a predicted time required to produce a 30% intervention decline
      being approximately 5 (4.0, 6.4) and approximately 3.6 (2.8, 4.8) years,
      respectively. To achieve this magnitude of decline, the client and FSW HIV
      prevalence needed to decrease by 33% (28%, 38%) and 44% (38%, 50%), respectively,
      after three years. CONCLUSION: Despite the optimistic prevention parameters
      assumed, our results suggest that the large observed changes in ANC HIV
      prevalence are very unlikely to already be entirely caused by the FSW targeted
      intervention. Interpretation of HIV trends in ANC populations should involve
      triangulation of observed biological and behavioural trends in high-risk groups,
      modeling studies and documentation of possible sources of bias.

PMID- 19098476
TI  - The impact of out-migrants and out-migration on the HIV/AIDS epidemic: a case
      study from south-west India.
AB  - OBJECTIVE: Seasonal migration may be an important driver of the HIV epidemic in
      India; however, migrant sexual behaviour data are limited. This study assessed
      the extent to which migration could explain heterogeneity in HIV prevalence in
      Bagalkot district, in Karnataka state, India, examining important migration
      related risk factors for HIV transmission and implications for prevention.
      DESIGN: We used mathematical modelling to explore the potential impact of
      different seasonal migration patterns on HIV prevalence. METHODS: A deterministic
      compartmental mathematical model of heterosexually transmitted HIV infection was
      developed. Six migration scenarios were explored, depending on which population
      migrated (men/clients only/female sex workers; FSW), and which local population
      determined the demand for commercial sex while migrants were away. RESULTS: The
      impact of migration varied substantially across the six migration scenarios.
      Migration was unlikely to explain heterogeneity in HIV prevalence unless a
      fraction of all men migrated and local FSW drove the demand for commercial sex.
      Even with very high-risk migrant sexual behaviour in the migration destination,
      targeting interventions at 30%-100% of local core groups could prevent a maximum
      of 12%-40% of new infections (87% effective condoms), from 2004-2015. Targeting
      migrants locally and at their destination could have up to 1.6-times the impact
      of targeting migrants only at their destination. CONCLUSIONS: Results suggest
      that core group interventions introduced locally because of the difficulty of
      reaching migrant populations could still be beneficial. Understanding how local
      sexual networks change during migration is crucial for understanding the impact
      of migration on HIV transmission, and for designing HIV preventive interventions.

PMID- 19098474
TI  - Appropriateness and execution challenges of three formal size estimation methods
      for high-risk populations in India.
AB  - OBJECTIVES: To describe formal, external to programme methods for size estimation
      of high-risk populations and compare execution challenges and validity of
      results. DESIGN: A cross-sectional HIV risk behavioural and biological survey was
      implemented among 24, 10 and five female sex workers, high-risk men who have sex
      with men and injecting drug user survey groups, respectively. Size estimates were
      calculated using three formal methods: capture-recapture, the multiplier method
      and the reverse tracking method (RTM), a new method. METHODS: Estimates were
      compared with each other and programme data. RESULTS: In general, when
      appropriately executed, formal methods produced smaller estimates to programme
      data, although the RTM tended to be closer to programme estimates. CONCLUSIONS:
      Capture-recapture requires some knowledge of site location. It can be used as a
      community mobilization measure at the initiation of a programme. The multiplier
      method presumes the existence of high quality external data and requires care in
      selecting the appropriate multiplier. All size estimation methods require careful
      planning and a full understanding of population dynamics and limitations of data.
      Before selecting a size estimation method, one must be aware of the strengths,
      weaknesses and applicability of each method. Use of size estimation methods in
      large-scale programmes should be considered carefully with adequate importance
      given to planning and implementation.

PMID- 19098477
TI  - Baseline integrated behavioural and biological assessment among most at-risk
      populations in six high-prevalence states of India: design and implementation
      challenges.
AB  - OBJECTIVE: This paper presents key methodological approaches and challenges in
      implementing and analysing the first round of the integrated biobehavioural
      assessment of most-at-risk populations, conducted in conjunction with evaluation
      of Avahan, the India AIDS initiative. METHODS: The survey collected data on HIV
      risk behaviours, sexually transmitted infections and HIV prevalence in 29
      districts in six high-prevalence states of India. Groups included female sex
      workers and clients, men who have sex with men, injecting drug users and truck
      drivers. Strategies for overcoming some challenges of the large-scale surveys
      among vulnerable populations, including sampling hidden populations, involvement
      of the communities targeted by the survey, laboratory and quality control in
      remote, non-clinic field settings, and data analysis and data use are presented.
      DISCUSSION: Satisfying the need for protocols, guidelines and tools that allowed
      for sufficient standardization, while being tailored enough to fit diverse local
      situations on such a large scale, with so many implementing partners, emerged as
      a major management challenge. A major lesson from the first round is the vital
      importance of investing upfront time in tailoring the sampling methods, data
      collection instruments, and analysis plan to match measurement objectives.
      CONCLUSION: Despite the challenges, the integrated biobehavioural assessment was
      a huge achievement, and was largely successful in providing previously
      unavailable information about the HIV situation among populations that are
      critical to the curtailment of HIV spread in India. Lessons from the first round
      will be used to evolve the second round into an exercise with increased
      evaluative capability for Avahan.

PMID- 19098478
TI  - Determinants of HIV prevalence among female sex workers in four south Indian
      states: analysis of cross-sectional surveys in twenty-three districts.
AB  - OBJECTIVE: In four states in southern India we explored the determinants of HIV
      prevalence among female sex workers (FSW), as well as factors associated with
      district-level variations in HIV prevalence among FSW. METHODS: Data from cross
      sectional surveys in 23 districts were analysed, with HIV prevalence as the
      outcome variable, and sociodemographic and sex work characteristics as predictor
      variables. Multilevel logistic regression was applied to identify factors that
      could explain variations in HIV prevalence among districts. RESULTS: HIV
      prevalence among the 10 096 FSW surveyed was 14.5% (95% confidence interval 14.0
      15.4), with a large interdistrict variation, ranging from 2% to 38%. Current
      marital status and the usual place of solicitation emerged as important factors
      that determine individual probability of being HIV positive, as well as the HIV
      prevalence within districts. In multivariate analysis, compared with home-based
      FSW, the odds of being HIV positive was greater for brothel-based FSW [adjusted
      odds ratio (AOR) 2.17, P <or= 0.001] and for public place-based FSW (AOR 1.32, P
      = 0.005). Unmarried FSW and those who were widowed/divorced/separated, or from
      the devadasi tradition, had higher odds of being HIV positive (AOR 1.79, P <or=
      0.001 and 1.98, P < 0.001, respectively), than those currently married. The
      estimated district level variance in HIV prevalence was lowest (0.152) for
      brothel-based unmarried FSW, followed by brothel-based widowed/divorced/separated
      or devadasi FSW (0.192). CONCLUSION: Heterogeneity in the organization and
      structure of sex work is an important determinant of variations in HIV prevalence
      among FSW across districts in India, much more so than the districts themselves.
      This understanding should help to improve the design of HIV preventive
      interventions.

PMID- 19098479
TI  - Sexual practices, HIV and sexually transmitted infections among self-identified
      men who have sex with men in four high HIV prevalence states of India.
AB  - OBJECTIVE: To describe the sociodemographic characteristics, prevalence of high
      risk sexual behaviours, HIV, sexually transmitted infections (STI), and
      perception of risk in self-identified men who have sex with men (MSM) in four
      south Indian states. METHODS: A cross-sectional probability-based survey of 4597
      self-identified MSM in selected districts from four states in south India was
      undertaken. Self-defined sexual identity, sexual behaviour, and STI/HIV knowledge
      were assessed using a structured questionnaire. Blood and urine samples were
      tested for HIV and STI. Recruitment criteria differed slightly across states.
      RESULTS: When grouped by self-identity, the HIV prevalence was: hijra
      (transgender) 18.1%; bisexuals 15.9%; kothis (anal-receptive) 13.5%; double
      deckers (both anal-insertive/anal-receptive) 10.5%; and panthis (anal-insertive)
      7.6%. Reported condom use with last paid male partner was over 80% in all states
      and categories. Consistent condom use was overall low among self-identified MSM,
      with less than 29% with non-commercial non-regular male partners and less than
      49% with regular male partners. The percentage of self-identified MSM with
      regular female partners was 4-43% and with commercial female partners was 14-36%
      across states, and consistent condom use differed by self-identity. Syphilis
      prevalence was high among kothis and hijras (15.8 and 13.6%, respectively).
      Urethral gonorrhoea prevalence was less than 1% and chlamydia prevalence ranged
      from 0.4 to 4.0%. CONCLUSION: HIV prevalence and risk behaviour within these self
      identified MSM communities in south India is high. Moreover, a significant
      proportion of them had female partners, both regular and commercial. The national
      programme's focus on HIV prevention services for these high-risk MSM is
      justified.

PMID- 19098480
TI  - Injecting and sexual risk behaviours, sexually transmitted infections and HIV
      prevalence in injecting drug users in three states in India.
AB  - OBJECTIVE: To describe and compare sexual and injecting risk behaviours and
      sexually transmitted infections (STI), hepatitis C virus (HCV) and HIV prevalence
      in injecting drug users (IDU) in six districts in three states of India: Manipur,
      Nagaland, and Maharashtra. METHOD: The respondent-driven sample consisted of 2075
      IDU. Consenting participants were administered a structured questionnaire and
      samples of blood and urine were collected to test for HIV and STI. Data were
      analysed using RDSAT. RESULTS: In two districts in Manipur, 77 and 98% of IDU
      injected heroin, whereas the main injecting drug in Nagaland was
      dextropropoxyphene (99%). In Mumbai/Thane, Maharashtra, the majority of
      respondents reported using chlorpheniramine (87%) and heroin (99%). In all
      districts, almost half of IDU reported generally sharing needles and syringes;
      consistent condom use with non-paid female partners was also low. Approximately
      one-quarter of IDU in Mumbai/Thane visited a paid partner in the past year. IDU
      with reactive syphilis serology were higher in Nagaland (7 and 19%) than in
      Manipur and Maharashtra. HIV in two districts of Manipur (23%, 32%) and
      Mumbai/Thane (16%) was greater than Nagaland (<2%). HCV prevalence was more than
      50% in Mumbai/Thane and Manipur. CONCLUSION: Irrespective of regional
      differences, high-risk behaviour of needle sharing and low condom use makes IDU a
      critical subpopulation for HIV prevention interventions. Interventions need to
      address the differing drug use patterns in the regions and transmission
      prevention among non-paid regular and casual female partners of IDU in the
      northeast districts and paid female partners in Mumbai/Thane.

PMID- 19098483
TI  - Declines in risk behaviour and sexually transmitted infection prevalence
      following a community-led HIV preventive intervention among female sex workers in
      Mysore, India.
AB  - OBJECTIVE: To investigate the impact on sexual behaviour and sexually transmitted
      infections (STI) of a comprehensive community-led intervention programme for
      reducing sexual risk among female sex workers (FSW) in Mysore, India. The key
      programme components were: community mobilization and peer-mediated outreach;
      increasing access to and utilization of sexual health services; and enhancing the
      enabling environment to support programme activities. METHODS: Two cross
      sectional surveys among random samples of FSW were conducted 30 months apart, in
      2004 and 2006. RESULTS: Of over 1000 women who sell sex in Mysore city, 429
      participated in the survey at baseline and 425 at follow-up. The median age was
      30 years, median duration in sex work 4 years, and the majority were street based
      (88%). Striking increases in condom use were seen between baseline and follow-up
      surveys: condom use at last sex with occasional clients was 65% versus 90%, P <
      0001; with repeat clients 53% versus 66%, P < 0.001; and with regular partners 7%
      versus 30%, P < 0.001. STI prevalence declined from baseline to follow-up:
      syphilis 25% versus 12%, P < 0.001; trichomonas infection 33% versus 14%, P <
      0.001; chlamydial infection 11% versus 5%, P = 0.001; gonorrhoea 5% versus 2%, P
      = 0.03. HIV prevalence remained stable (26% versus 24%), and detuned assay
      testing suggested a decline in recent HIV infections. CONCLUSION: This
      comprehensive HIV preventive intervention empowering FSW has resulted in striking
      increases in reported condom use and a concomitant reduction in the prevalence of
      curable STI. This model should be replicated in similar urban settings across
      India.

PMID- 19098484
TI  - HIV pathogenesis: 25 years of progress and persistent challenges.

PMID- 19098481
TI  - HIV, sexually transmitted infections and sexual behaviour of male clients of
      female sex workers in Andhra Pradesh, Tamil Nadu and Maharashtra, India: results
      of a cross-sectional survey.
AB  - OBJECTIVE: To characterize and describe patterns of HIV, sexually transmitted
      infections (STI) and sexual behaviour of male clients of female sex workers
      (FSW). METHODS: A cross-sectional study was conducted among 4821 clients of FSW
      from 12 districts in three states in India: Andhra Pradesh, Maharashtra and Tamil
      Nadu. A structured questionnaire was administered to elicit demographic
      characteristics and sexual behavioural patterns. Blood and urine samples were
      tested for HIV, syphilis and herpes simplex type 2 serology, gonococcal and
      chlamydial infection. RESULTS: The median age of clients surveyed was 30 years;
      57% were married and 64% had a steady sexual partner; 61% had sex with more than
      one FSW and 39% had four or more sexual encounters in the past month. The
      prevalence of HIV ranged from 2.0% to 10.9%, syphilis ranged from 3.1% to 10.1%;
      gonorrhoea and chlamydia ranged between 0% and 4.5%. Clients older than 30 years
      [odds ratio (OR) 1.65; 95% confidence interval (CI) 1.33-2.05] and having a
      different mix of commercial and non-commercial partners (OR 1.56; 95% CI 1.25
      1.96) had a higher volume of sex acts with FSW. Inconsistent condom use with FSW
      was significantly associated with older clients (OR 4.2; 95% CI 3.33-5.29),
      illiteracy (OR 1.39; 95% CI 1.14-1.69), age <18 years at first paid sex (OR 1.83;
      95% CI 1.24-2.70) and having different FSW partners in the past month (OR 1.64;
      95% CI 1.23-2.18). CONCLUSION: Clients of FSW studied here constitute a
      significant bridge group for HIV and other STI, because of their high volume of
      different sexual partners and very low consistent condom use. HIV prevention
      programmes need to address male clients.

PMID- 19098482
TI  - Risk behaviour, sexually transmitted infections and HIV among long-distance truck
      drivers: a cross-sectional survey along national highways in India.
AB  - OBJECTIVE: To report HIV and sexually transmitted infection (STI) prevalence and
      sexual behaviour of long-distance truckers on four national highway routes from a
      large, cross-sectional, national-level trucker survey in India. METHODS: Seven
      trans-shipment locations covering the bulk of India's transport volume along four
      routes, north-west (NW), north-south (NS), north-east (NE) and south-east (SE)
      were identified as survey sites. A total of 2066 long-distance truckers were
      selected using a two-stage, time-location cluster sampling approach and, after
      consent, interviewed about their sexual behaviour. Urine and blood sample were
      tested for selected STIs. RESULTS: Overall, HIV prevalence among truckers was
      found to be 4.6%, with prevalence highest on the SE route (6.8%) and lowest on
      the NS (2.4%). Positive HSV-2 serology, which was tested in a 10% subsample, was
      low along three routes, 10.0%, 12.8% and 6.7% for the NE, NS and NW,
      respectively, but 38.7% in the SE. The truckers from the SE were found to be more
      likely to have sex with paid partners than the NE route. Moreover, truckers who
      owned their trucks were more likely than those who did not use condoms
      consistently with paid partners, and truckers who drive trucks owned by their
      relatives/friends are more likely than others to have any STI. CONCLUSIONS: Low
      self-risk perception for HIV (9.9%), low consistent condom use with non-paid
      partners (18.6%) and wives (3%), low reported exposure to any interventions
      (25.6%) and low levels of ever having taken an HIV test (16.5%) make truckers an
      important bridge population requiring strengthened interventions.

PMID- 19098485
TI  - The 'immunologic advantage' of HIV-exposed seronegative individuals.

PMID- 19098486
TI  - Association between HLA-G 3'UTR 14-bp polymorphism and HIV vertical transmission
      in Brazilian children.
AB  - OBJECTIVES: The aim of our study was to verify the possible association between
      an HLA-G 14-bp deletion/insertion polymorphism and perinatal HIV transmission in
      Brazilian children. DESIGN: We analyzed the 14-bp deletion/insertion
      polymorphisms in seronegative (i.e., exposed uninfected, N = 71) and seropositive
      (exposed infected, N = 175) Brazilian children born from HIV-positive mothers and
      in healthy controls (n = 175). METHODS: HLA-G 14-bp deletion/insertion
      polymorphism (rs16375) was detected by PCR amplification of the target sequence
      followed by agarose gel electrophoresis. All the samples were also analyzed by
      direct sequencing in order to validate the genotyping results. RESULTS: HIV
      exposed uninfected children showed significant differences in their allele and
      genotype frequencies of the HLA-G 14-bp polymorphism when compared to both
      seropositive children and healthy controls. The 14-bp-deleted (D) allele was more
      frequent in exposed uninfected children (79%) than in healthy controls (60%) and
      HIV-positive children (58%); the higher percentage of the D allele found in the
      exposed uninfected children with respect to HIV-positive individuals was
      significantly associated with a reduced risk of vertical transmission. This
      effect was ascribable to the presence of the D/D homozygous genotype. CONCLUSION:
      Our findings support the possible role for the HLA-G 14-bp deletion/insertion
      polymorphism in the HIV vertical transmission in Brazilian children. The presence
      of the D allele and D/D genotype is associated with a protective effect toward
      HIV perinatal infection.

PMID- 19098487
TI  - Antigp41 antibodies fail to block early events of virological synapses but
      inhibit HIV spread between T cells.
AB  - OBJECTIVE: Compared with cell-free viral infection, virological synapses increase
      HIV capture by target cells, viral infectivity and cytopathicity, and are
      believed to be less sensitive to antibody neutralization. We have evaluated the
      impact of antibodies against HIV envelope glycoproteins (gp120 and gp41) on cell
      to-cell HIV transmission. METHODS: We analyzed the role of trogocytosis in cell
      to-cell HIV transmission and the inhibitory mechanisms of antigp120 antibody
      IgGb12 and antigp41 antibodies 4E10 and 2F5 using cocultures of NL4-3 or BaL
      infected MOLT/CCR5 cells with primary CD4 T cells. RESULTS: Analysis of early
      steps of HIV transmission in these cocultures showed that IgGb12, but not 4E10
      and 2F5, inhibited the formation of virological synapses. Consequently, IgGb12
      but not antigp41 antibodies blocked the transfer of HIV particles from infected
      to target cells and the trogocytic transfer of CD4 molecules from target to
      infected cells. Interestingly, trogocytic transfer of membranes was not detected
      in the HIV transmission direction. Furthermore, analysis of late events of HIV
      transmission showed that all neutralizing antibodies blocked productive infection
      of target cells, suggesting that HIV infection between T cells is transmitted by
      a neutralization-sensitive mechanism involving HIV budding from infected cells
      and capture by target cells. CONCLUSION: Despite mechanistic differences,
      antigp120 and antigp41 antibodies block infectious cell-to-cell HIV transmission.
      Our data suggest that eliciting high titers of neutralizing antibodies in vivo
      should be maintained as a main end of HIV vaccine design.

PMID- 19098488
TI  - Reciprocal recognition of an HLA-Cw4-restricted HIV-1 gp120 epitope by CD8+ T
      cells and NK cells.
AB  - OBJECTIVES: The HIV-1 Nef protein selectively downregulates human leukocyte
      antigen (HLA)-A and HLA-B but not HLA-C molecules on the surface of infected
      cells. This allows HIV-infected cells to evade recognition by most cytotoxic T
      lymphocytes (CTLs) and natural killer (NK) cells. We investigated the recognition
      of an HLA-Cw4-restricted HIV-1 gp120 epitope SFNCGGEFF (SF9) and its variant
      SFNCGGEFL (SL9) by T cells and NK receptors. DESIGN AND METHOD: Recognition of
      HIV-1 gp120 peptides (SF9 and SL9) by T-cell clones was measured by staining with
      HLA-Cw4-peptide tetrameric complexes and cytolytic assays using target cell
      pulsed with either peptides. KIR2DL1 binding to these two peptides was measured
      using surface plasmon resonance and tetramer staining of an NK cell line. RESULT:
      : CTLs could recognize SF9 better than the variant SL9, as shown by both tetramer
      staining and cytolytic assays. Intriguingly, an HLA-Cw4 tetramer folded with the
      'escape' variant SL9 could bind to KIR2DL1 on NK cell lines with higher affinity
      than HLA-Cw4-SF9. The binding of KIR2DL1 to its ligand results in inhibition of
      NK cell function. Our results indicate that the HIV-1 gp120 variant peptide SL9
      could potentially escape both from NK cell and CTL recognition by increasing its
      affinity for KIR2DL1 binding. CONCLUSION: These data suggest that HIV-1 can
      acquire mutations that are capable of escaping from both CTL and NK cell
      recognition, a phenomenon we have termed 'double escape'.

PMID- 19098489
TI  - The impact of the President's Emergency Plan for AIDS Relief on expansion of HIV
      care services for adult patients in western Kenya.
AB  - BACKGROUND: The President's Emergency Plan for AIDS Relief committed $15 billion
      to addressing HIV in resource-poor settings. OBJECTIVE: To assess the impact of
      The President's Emergency Plan for AIDS Relief on the treatment services of an
      HIV care program. DESIGN, SETTING, AND PATIENTS: Cohort study utilizing
      computerized medical records of nonpregnant adults enrolled into the Academic
      Model for the Prevention and Treatment of HIV/AIDS system, in western Kenya
      between 27 November 2001 and 24 July 2006. MAIN OUTCOMES MEASURES: Number of
      clinics and patients enrolled in Academic Model for the Prevention and Treatment
      of HIV/AIDS, as well as patient demographics, immunologic, and clinical
      characteristics during three periods defined by the availability of combination
      antiretroviral therapy (cART). RESULTS: Enrollment as of May 2006 was 23,539.
      Mean monthly enrollment increased from 64 to 815 between periods 1 and 3. The
      median CD4 cell count at enrollment during period 3 (172 cells/microl) was
      significantly higher than for period 2 (119 cells/microl; P < 0.001). World
      Health Organization stage at enrollment differed significantly between periods
      with 6.7% having stage 4 disease in period 3 compared with 13.8% during period 1
      (P < 0.001). Significantly more patients had complete documentation of cART
      eligibility, during period 3 as compared with the previous periods. Time from
      enrollment to cART initiation decreased from a median of 64 weeks in period 1 to
      12 weeks during period 3 (P < 0.001). CONCLUSION: The President's Emergency Plan
      for AIDS Relief funding has allowed Academic Model for the Prevention and
      Treatment of HIV/AIDS to significantly increase the number of individuals
      receiving HIV care and provided the ability to expand services allowing for
      identification of patients earlier in their disease process.

PMID- 19098491
TI  - Oligonucleotide-mediated retroviral RNase H activation leads to reduced HIV-1
      titer in patient-derived plasma.
AB  - BACKGROUND: The retroviral RNase H is essential for viral replication. This
      component has not yet been extensively studied for antiviral therapy. It can be
      activated by an oligodeoxynucleotide (ODN) resulting in self-destruction of the
      virions. OBJECTIVE: To examine antiviral potential of ODN in clinical samples
      using plasma of HIV-1-infected patients. DESIGN: Plasma of 19 HIV-1-infected
      patients from Zurich and 10 HIV-1 isolates from Africa and drug-resistant strains
      were processed for ex-vivo treatment. METHODS: Cell-free virions were treated
      with ODN in the plasma and HIV RNA was measured by quantitative reverse
      transcription polymerase chain reaction (qRT-PCR). Furthermore, infectivity of
      the treated virions was tested on primary human peripheral blood mononuclear
      cells. RESULTS: Cell-free virions in plasma contained significantly less intact
      HIV RNA upon treatment with ODN (P = 0.0004), and their infectivity was decreased
      52-fold (P = 0.0004). In 39% of the Zurich samples, infectivity was reduced more
      than 10-fold, in 33% more than 100-fold, and in 28% more than 1000-fold. Also,
      the isolates from Africa exhibited a 63-fold reduction in infectivity (P =
      0.0069) with 80% of the isolates responding more than 10-fold, 40% more than 100
      fold, and 10% more than 1000-fold. CONCLUSION: Significant reduction of plasma
      HIV RNA levels and infectivity of treated virions was achieved on the basis of
      induced self-destruction of HIV observed with clinical samples. Reduction of
      viral load ex vivo was designed as model for potential effects in vivo. Premature
      activation rather than inhibition of a viral enzyme could be a model strategy for
      future antiretroviral control.

PMID- 19098490
TI  - Inferiority of IL-2 alone versus IL-2 with HAART in maintaining CD4 T cell counts
      during HAART interruption: a randomized controlled trial.
AB  - OBJECTIVE: To evaluate whether interleukin (IL)-2 in patients with chronic HIV
      infection can maintain CD4 T cell counts during 6 months of HAART interruption.
      DESIGN: Prospective, randomized, controlled, open-label phase II noninferiority
      trial comparing IL-2 with HAART interruption or continuous HAART. METHODS: Forty
      one IL-2-experienced (three or more prior cycles) HIV-1-infected adults with CD4
      cell count at least 500 cells/microl were randomized in the ratio 2: 1 to
      interrupted (I = 27) or continuous (C = 14) HAART for 6 months following an
      initial IL-2 cycle. Subsequent IL-2 cycles were triggered by CD4 T cell counts
      less than 90% of baseline. Immune, metabolic, and quality of life indices were
      compared (Mann-Whitney and Fisher's exact tests), defining noninferiority as a
      percentage difference (C- I) in treatment success (CD4 T cells > or =90% of
      baseline at 6 months) with a 95% confidence interval (CI) lower limit greater
      than -20%. RESULTS: Demographic and immune parameters were similar between the
      groups at baseline. Median CD4 T cell count, HIV viral load, and treatment
      success differed significantly at 6 months (I: 866 cells/microl, 39,389
      copies/ml, 48.1%; C: 1246 cells/microl, <50 copies/ml, 92.3%; P < or = 0.001).
      Group I was inferior to C (% difference = -44.2%; 95% CI: -64.2%, -11.2%; P =
      0.013). Minor statistically significant differences in HgbA1c and energy level
      occurred at 6 months (I > C). Following HAART interruption, single cases of acute
      retroviral syndrome, secondary syphilis, non-Hodgkin's lymphoma, and Kaposi's
      sarcoma recurrence were observed. CONCLUSION: IL-2 alone was inferior to IL-2
      with HAART in maintaining baseline CD4 T cell counts. HAART interruption had a
      small impact on metabolic parameters and quality of life.

PMID- 19098492
TI  - New findings on blockage of HIV-1 RNase H activity.

PMID- 19098493
TI  - A public health model for the molecular surveillance of HIV transmission in San
      Diego, California.
AB  - BACKGROUND: Current public health efforts often use molecular technologies to
      identify and contain communicable disease networks, but not for HIV. Here, we
      investigate how molecular epidemiology can be used to identify highly related HIV
      networks within a population and how voluntary contact tracing of sexual partners
      can be used to selectively target these networks. METHODS: We evaluated the use
      of HIV-1 pol sequences obtained from participants of a community-recruited cohort
      (n = 268) and a primary infection research cohort (n = 369) to define highly
      related transmission clusters and the use of contact tracing to link other
      individuals (n = 36) within these clusters. The presence of transmitted drug
      resistance was interpreted from the pol sequences (Calibrated Population
      Resistance v3.0). RESULTS: Phylogenetic clustering was conservatively defined
      when the genetic distance between any two pol sequences was less than 1%, which
      identified 34 distinct transmission clusters within the combined community
      recruited and primary infection research cohorts containing 160 individuals.
      Although sequences from the epidemiologically linked partners represented
      approximately 5% of the total sequences, they clustered with 60% of the sequences
      that clustered from the combined cohorts (odds ratio 21.7; P < or = 0.01). Major
      resistance to at least one class of antiretroviral medication was found in 19% of
      clustering sequences. CONCLUSION: Phylogenetic methods can be used to identify
      individuals who are within highly related transmission groups, and contact
      tracing of epidemiologically linked partners of recently infected individuals can
      be used to link into previously defined transmission groups. These methods could
      be used to implement selectively targeted prevention interventions.

PMID- 19098495
TI  - Non-condom use risk-reduction behaviours: can they help to contain the spread of
      HIV infection among men who have sex with men?

PMID- 19098494
TI  - Unprotected anal intercourse, risk reduction behaviours, and subsequent HIV
      infection in a cohort of homosexual men.
AB  - OBJECTIVE: A range of risk reduction behaviours in which homosexual men practise
      unprotected anal intercourse (UAI) has been described. We aimed to assess the
      extent of any reduction in HIV risk associated with these behaviours. DESIGN: A
      prospective cohort study of HIV-negative homosexual men in Sydney, Australia.
      METHODS: Men were followed up with 6-monthly detailed behavioural interviews and
      annual testing for HIV. The four risk reduction behaviours (behaviourally
      defined) examined were serosorting, negotiated safety, strategic positioning, and
      withdrawal during receptive UAI (UAI-R). RESULTS: In 88% of follow-up periods in
      which UAI was reported, it occurred in the context of consistent risk reduction
      behaviours. Compared with those who reported no UAI, the risk of HIV infection
      was not raised in negotiated safety [hazard ratio = 1.67, 95% confidence interval
      (CI) 0.59-4.76] and strategic positioning (hazard ratio = 1.54, 95% CI 0.45
      5.26). Serosorting outside negotiated safety was associated with an intermediate
      rate of HIV infection (hazard ratio = 3.11, 95% CI 1.09-8.88). Withdrawal was
      associated with a higher risk than no UAI (hazard ratio = 5.00, 95% CI 1.94
      12.92). Patterns of UAI differed greatly according to partner's serostatus. Men
      who reported serosorting were less likely to report either strategic positioning
      or withdrawal. CONCLUSION: Each behaviour examined was associated with an
      intermediate HIV incidence between the lowest and highest risk sexual behaviours.
      The inverse association between individual behaviours suggests that men who
      practise serosorting rely on this protection. The high prevalence of these
      behaviours demands that researchers address the contexts and risks associated
      with specific types of UAI.

PMID- 19098496
TI  - Urinary cystatin C can improve the renal safety follow-up of tenofovir-treated
      patients.
AB  - A receiver operating curve analysis was performed to assess the predictive value
      of the urinary cystatin C to urinary creatinine ratio for the renal monitoring of
      tenofovir. Urinary cystatin C to urinary creatinine ratio was measured in 37
      samples from patients referred for suspected tenofovir-induced Fanconi syndrome.
      The best threshold (14 microg/mmol) was associated with sensitivity, 90.9%;
      specificity, 88.5%; positive predictive value, 76.9%; and negative predictive
      value, 95.8%. Urinary cystatin C to urinary creatinine ratio allows to rule out a
      Fanconi syndrome in most cases; thus, it should be used for the safety follow-up
      of nucleotide reverse transcriptase inhibitor-treated patients.

PMID- 19098497
TI  - Epidemiologically linked transmission of HIV-1 illustrates the impact of host
      genetics on virological outcome.
AB  - The diversity of HIV-1 and human genetics complicates our ability to determine
      the impact of treatment during primary HIV-1 infection on disease outcome. Here,
      we show, in a small group infected with virtually identical HIV-1 strains and
      treated during primary HIV-1 infection, that patients expressing protective human
      leucocyte antigen alleles had lower viral loads following treatment
      discontinuation. These data suggest that genetic factors play an important role
      in the outcome of HIV-1 infection despite early therapy.

PMID- 19098498
TI  - United Kingdom acquisition of HIV infection in African residents in London: more
      than previously thought.
AB  - Between a quarter to a third of HIV-positive African residents in the UK, and
      nearly half of HIV-positive African men who have sex with men, may have acquired
      their HIV infection in the UK, which is substantially higher than previously
      estimated. These estimates are likely to worsen given the increasing HIV
      prevalence and assortative sexual mixing in this community, especially among
      heterosexuals. HIV prevention interventions for Africans must focus on reducing
      transmission within the UK as well as addressing infections acquired abroad.

PMID- 19098499
TI  - Molecular analysis of an HBsAg-negative hepatitis B virus mutant selected in a
      tenofovir-treated HIV-hepatitis B virus co-infected patient.
AB  - The molecular analysis performed in an HIV-hepatitis B virus (HBV) coinfected
      patient revealed selection of an unusual HBV polymerase mutation (rtV191I) during
      tenofovir-containing therapy, conferring simultaneously immune escape by HBsAg
      negativity and resistance to lamivudine but not tenofovir. Phenotypic analysis
      revealed impaired replicative capacity of mutants, which could be restored by
      concomitant precore or basal core promoter mutations (HBe-antigen-negativity).
      HBV mutants carrying drug and vaccine resistance may represent a considerable
      individual risk and public health concern.

PMID- 19098500
TI  - Nonsmoking and other cofactors for Kaposi's sarcoma.

PMID- 19098501
TI  - Efavirenz-induced osteomalacia.

PMID- 19098502
TI  - Which helminth coinfections really affect HIV disease progression?

PMID- 19098504
TI  - Notes from the board: President's message.

PMID- 19098505
TI  - The space between us.

PMID- 19098506
TI  - Community graduates no longer have option of CNS exam.

PMID- 19098508
TI  - Patient outcomes using a rapid response team.

PMID- 19098507
TI  - Decision support and the clinical nurse specialist.

PMID- 19098509
TI  - Quitting smoking without a psychotic break: the potential link between nicotinic
      acetylcholine receptor partial agonists and neuropsychiatric adverse events.

PMID- 19098510
TI  - Promoting evidence-based practice through a traveling journal club.
AB  - BACKGROUND/RATIONALE: Lifelong learning is essential in today's work world, with
      the rapid explosion of knowledge and technology. Busy nurses find the challenge
      overwhelming to keep pace with current practice. Journal clubs work within
      inpatient settings but not for ambulatory nurses where the pace is much
      different. DESCRIPTION OF THE PROJECT/INNOVATION: A group consisting of 2
      clinical nurse specialists and the director of nursing research developed the
      concept of a traveling journal club where articles were selected specific to the
      needs of the population served by ambulatory nurses. Articles were selected on
      the basis of the complete review of the literature, evidence-based practice
      recommendations, and implications for practice. OUTCOME: A poster board was
      developed, an article was selected, and the board made the rounds to 7 ambulatory
      sites. Nurses appreciated the efforts by the group and found the traveling
      journal club to be worthwhile. INTERPRETATION/CONCLUSION: Methods of presenting
      materials to nurses in different work areas need to consider presenting the best
      approach to fit with the work flow and patient needs. Busy nursing inpatient and
      ambulatory settings do not have the luxury of time to sit, discuss, and critique
      literature. Alternative methods should be developed to assist the nurses in
      meeting their lifelong learning needs. IMPLICATIONS: The traveling journal club
      idea was adopted by the inpatient units that face similar issues with time and
      patient needs. The traveling journal club was a success in the setting originally
      planned and extended to other areas.

PMID- 19098511
TI  - Graduated compression stocking and intermittent pneumatic compression device
      length selection.
AB  - PURPOSE: The purpose of this project was to incorporate current evidence into
      length selection for graduated compression stockings (GCS) and intermittent
      pneumatic compression (IPC) devices in order to evaluate and modify current
      practice. RATIONALE: Staff nurses relate concerns regarding the fit and
      complications related to poorly fitting thigh length GCS and IPC devices. Current
      evidence supports using knee length over thigh length. DESCRIPTION OF THE
      PROJECT: With the use of Melnyk and Fineout-Overholt's model of evidence-based
      practice and Norwood's consultation model, current practice was evaluated and
      practice changes were implemented based on results of a literature review.
      OUTCOME: Knee length will be selected instead of thigh length in general and
      urology surgery patients. The department of obstetrics and gynecology has taken
      the practice change under consideration. CONCLUSION: Knee-length GCS and IPC
      devices are as effective as thigh-length GCS and IPC devices, are more
      comfortable for patients, are easier for staff and patients to use, pose less
      risk of injury to patients, and are less expensive. Knee-length GCS and IPC
      devices may safely be used for general, gynecology, and urology surgery patients
      and are preferable to thigh-length GCS and IPC devices. IMPLICATIONS: Venous
      thromboembolism prophylaxis is an important component of surgical care; proper
      length selection of GCS and IPC devices should be based on current evidence. This
      project outlines a method to change practice regarding length selection of GCS
      and IPC devices.

PMID- 19098512
TI  - Selective optimization with compensation: a model for elder health programming.
AB  - The members of the independent and active baby boom generation entering their
      retirement years may put clinical nurse specialists (CNS) in greater demand than
      ever before as educators, consultants, researchers, and case managers. Community
      based educational programming to promote health and to monitor and manage chronic
      health conditions of elders is a recognized method for the CNS to meet these
      growing demands. The application and utilization of Baltes and Baltes'
      theoretical model of Selective Optimization With Compensation (SOC) in senior
      health programming holds promise for CNSs to assume more integral roles in
      optimizing health promotion for and self-actualization in community-living
      elders. Senior centers serve older adults who want to stay active, involved with
      others their age, and current, including learning how to promote their health.
      The CNS can readily infuse the SOC model into the planning and organizing of
      health programming for older adults at senior centers, which will in turn aid
      elders in maintaining independent functioning, autonomy, and quality of life. A
      detailed template for developing such theory-driven programming with an example
      program focused on nutrition is provided. Finally, a variety of topics for
      additional SOC-guided program development are presented.

PMID- 19098513
TI  - Readability and patient education materials used for low-income populations.
AB  - More than 90 million Americans have low levels of health literacy that may
      contribute to poor health outcomes. Assessment of the readability of patient
      education materials (PEMs) is a vital component of health education. PURPOSE: The
      aim of this study was to describe the readability of PEMs used in community
      healthcare settings serving low-income populations to provide further insight
      into the complex area of health literacy. DESIGN: A descriptive, correlational,
      and nonexperimental design was used for this study. SETTING: The setting for this
      study was 5 free and low-cost community clinics in a Midwestern urban area.
      SAMPLE: Thirty-five unique PEMs produced by professional sources (government
      agencies, drug companies, and state/national organizations) or by providers
      comprised the final sample. METHODS: Readability was measured using Simple
      Measure of Gobbledygook (SMOG), Flesch-Kincaid, and Flesch Reading Ease.
      Significance was determined through t tests and Spearman rho correlations.
      FINDINGS: Variability in grade levels was noted using all measures. Mean Flesch
      Kincaid grade level was 7.01, and that for SMOG was 9.89. Mean level for Flesch
      Reading Ease was 63.40, an estimated eighth and ninth grade level. The SMOG
      consistently measured 2 to 4 grades levels higher than did Flesh-Kincaid.
      Professionally developed PEMs had significantly higher reading levels using both
      SMOG and Flesch-Kincaid and were more difficult to read using Flesch Reading Ease
      when compared with those prepared by individual providers. CONCLUSIONS: Patient
      education materials were written at a level too high for the average adult. All
      PEMs should be analyzed carefully to ensure that they are at the recommended
      fifth grade level. Further understanding of available measures of readability is
      critical in the creation and/or assessment of PEMs that will strengthen services
      from safety net providers and support positive health outcomes. IMPLICATIONS:
      Nurses must expand their knowledge of all aspects of literacy and readability and
      take a proactive role in assessment and development of PEMs. Further research is
      needed to determine the best readability measures.

PMID- 19098515
TI  - Family and friends create hope and understanding for those with dementia.

PMID- 19098517
TI  - Skeletal muscle fatigue: the tortoise's advantage.

PMID- 19098518
TI  - Skeletal muscle fatigue in old age: whose advantage?
AB  - The results of recent studies indicate that in healthy men and women aged beyond
      approximately 65 years, the energy-producing pathways in skeletal muscle may
      combine with changes in motor unit behavior and muscle contractile properties to
      provide a unique environment for resisting muscle fatigue under some conditions.

PMID- 19098519
TI  - Striding toward social justice: the ecologic milieu of physical activity.
AB  - Disparities in physical activity should be investigated in light of social
      justice principles. This article critically evaluates evidence and trends in
      disparities research within an ecologic framework, focusing on multilevel factors
      such as neighborhood and racial discrimination that influence physical activity.
      Discussion focuses on strategies for integrating social justice into physical
      activity promotion and intervention programming within an ecologic framework.

PMID- 19098520
TI  - Dual and beneficial roles of macrophages during skeletal muscle regeneration.
AB  - Macrophages are necessary for skeletal muscle regeneration after injury. Muscle
      recruits inflammatory monocytes/macrophages that switch toward an anti
      inflammatory profile upon phagocytosis of debris. In vitro, proinflammatory
      macrophages stimulate myoblast proliferation, whereas anti-inflammatory
      macrophages stimulate their differentiation. Thus, macrophages are involved in
      both phases of skeletal muscle regeneration: first, inflammation and cleansing of
      necrosis, and then myogenic differentiation and tissue repair.

PMID- 19098521
TI  - Why eating less keeps mitochondria working in aged skeletal muscle.
AB  - The mechanisms by which caloric restriction preserves skeletal muscle health with
      aging continue to be explored; however, mounting evidence points toward a
      convergence of effects at the level of the mitochondrion. Specifically, caloric
      restriction reduces mitochondrial reactive oxygen species production and promotes
      mitochondrial renewal via enhanced drive on mitochondrial biogenesis and
      autophagy.

PMID- 19098523
TI  - Linking biomechanics to mobility and disability in people with knee
      osteoarthritis.
AB  - Knee osteoarthritis is the leading cause of chronic disability among community
      dwelling adults. The factors resulting in this disability extend beyond
      pathology. Therefore, understanding disability requires assessment of both
      pathology and the day-to-day consequences of knee osteoarthritis. This review
      develops a novel osteoarthritis construct, "careful mobility," by linking
      qualitative and quantitative methods to study both patient experience and
      biomechanics.

PMID- 19098522
TI  - Sarcoplasmic reticulum-mitochondrial symbiosis: bidirectional signaling in
      skeletal muscle.
AB  - In mammalian skeletal muscle, an intimate association between the sarcoplasmic
      reticulum (SR) and mitochondria results in a symbiotic and privileged
      bidirectional communication between these organelles. Orthograde signaling
      reflects SR calcium (Ca) release stimulating mitochondrial adenosine triphosphate
      production via excitation-metabolism coupling. Retrograde signaling involves
      mitochondrial inhibition of local SR Ca release by controlling the redox
      environment of the Ca release unit.

PMID- 19098524
TI  - Can robots help the learning of skilled actions?
AB  - Learning to move skillfully requires that the motor system adjusts muscle
      commands based on ongoing performance errors, a process influenced by the
      dynamics of the task being practiced. Recent experiments from our laboratories
      show how robotic devices can temporarily alter task dynamics in ways that
      contribute to the motor learning experience, suggesting possible applications in
      rehabilitation and sports training.

PMID- 19098525
TI  - Potential applications of pulsating joint loading in sports medicine.
AB  - Because bone is responsive to mechanical loading, pulsating joint loading (PJL),
      which laterally applies oscillatory mechanical loads to joints, can be explored
      for preventive conditioning and therapeutic treatments. Herein, the general
      features of PJL are reviewed, and its potential usage for sports medicine is
      discussed.

PMID- 19098528
TI  - Bone healing in the presence of implantable fixation devices in children and in
      adults.

PMID- 19098529
TI  - Educational value of the archives and the cumulative index of the published
      material.

PMID- 19098530
TI  - Use of diced bone grafts wrapped in surgicel in the augmentation of maxillofacial
      area.
AB  - The correction of asymmetry in craniomaxillofacial region presents many problems
      for reconstructive surgeons. For this purpose, varieties of different materials
      and techniques have been used. We present our experience with diced bone graft
      wrapped in Surgicel applied to 5 patients with facial atrophy due to various
      causes between the years 2005 and 2008. The average follow-up period was 18
      months (range, 9-25 months). All bone grafts were diced into small pieces with a
      maximum size of 2 to 3 mm using a costotome. The smaller bone grafts were
      prepared according to the technique described by Erol (Plast Reconstr Surg.
      2000;105:2229-2241) for cartilage grafts. Results of the patients' satisfaction
      were well. Wrapping bone grafts in Surgicel holds them together. Thus, it becomes
      easier to adapt the diced bone grafts to the area to be augmented. Molding of
      diced bone grafts wrapped in Surgicel in accordance with the three-dimensional
      structure of the face with gentle movements after adaptation is an important
      advantage, which classical bone grafts do not have. In the later periods,
      collagen-enhancing effect of Surgicel not only prevents the bone grafts' being
      noticed, but also softens its consistency. This in turn facilitates adaptation of
      bone grafts to the facial area.

PMID- 19098531
TI  - Osteomas of the maxillofacial district: endoscopic surgery versus open surgery.
AB  - Maxillofacial district osteomas are benign lesions with very slow growth. The
      most frequent localization is the frontal sinus, about 57% of all paranasal
      cavity osteomas; less frequently, they can be located in the ethmoidal sinus or
      sphenoidal and maxillary. Etiology has not completely clarified yet;
      nevertheless, there are 3 main pathogenetic theories: osteogenic, traumatic, and
      infective. Open procedures represent the gold standard, but there is still an
      unsolved debate for the best treatment option. Endoscopic techniques offer an
      alternative approach, enabling closer and more direct visualization of the
      anatomy as well as avoiding damage to surrounding structures. In our study, we
      analyzed all patients treated with endoscopic approach for paranasal sinus
      osteomas in the ENT unit of the University of Varese and compared them with
      patients treated for the same pathology with open surgery in the Maxillo-facial
      Department of the University of Rome "La Sapienza." The purpose of the work was
      to compare the advantages and disadvantages of the 2 procedures. In conclusion,
      this study underlines the importance of flexibility in surgical approach
      decision, which must fit the different issues of the pathology and of the
      patient.

PMID- 19098532
TI  - Sagittal synostotic twins: reverse pi procedure for scaphocephaly correction
      gives superior result compared to endoscopic repair followed by helmet therapy.
AB  - A unique situation of twins with similar sagittal synostosis pathology who
      underwent different surgical corrective procedures allowed us an opportunity to
      compare an endoscopic technique to the more traditional technique of a modified
      cranial vault remodeling (CVR). At 4 months of age, 1 twin underwent an
      endoscopic-assisted extended strip craniectomy with postoperative helmet therapy
      for 12 months, and the other underwent a reverse pi CVR procedure. Cephalic
      index, the Whitaker Aesthetic score, and developmental tests were used for
      comparison during a 6-year follow-up. The modified CVR had a superior outcome
      compared to the endoscopic procedure with regard to cephalic index measurements
      (CVR = 77; endoscopic = 63; P < 0.05) and the Whitaker score (CVR = 1 or no
      revisions necessary; endoscopic = 2.3 or minor to major bony work required for
      correction). Patients had similar intelligence quotient test scores; however, the
      endoscopic patient had lower scores in both preschool tests and global
      evaluations compared with the normal scores of the CVR patient. The modified CVR
      procedure was superior to the endoscopic procedure, at least in these twins with
      sagittal synostosis.

PMID- 19098533
TI  - Intraosseous hemangiomas.
AB  - Intraosseous hemangiomas are classified as benign tumors of vascular nature. Some
      authors describe them as hamartomas. They originate and expand inside bone
      structures. They are usually congenital, rarely of posttraumatic origin. In the
      Maxillo-Facial Surgery departments of the Universities of Rome "La Sapienza" and
      "Tor Vergata," from 1990 to 2004, 11 cases of intraosseous hemangioma have been
      diagnosed. In 6 cases, the neoplasm localized in the zygomatic region; in 3
      cases, at the mandible level; in 1 patient, in the maxillary site; and in 1
      patient, in the frontal bone. Literature review and the case of a male patient
      affected by left orbitozygomatic hemangioma are described.

PMID- 19098534
TI  - Prediction of transverse maxillary dimension using orthodontic models.
AB  - The main objective of this study was to quantify the transverse maxillary
      dimensions using orthodontic cast models of individuals with natural normal
      occlusion. Sixty-eight pairs of orthodontic models were evaluated with the
      respective posteroanterior radiographies of white adults (38 women and 30 men;
      mean age, 17 years and 5 months). The models were placed in Class I molar
      occlusion, and on each pair, 4 points were marked on the alveolar buccal ridge (2
      on the premolar region and 2 on the molar), determining the upper and lower
      transverse interpremolar and intermolar dimensions. The variables analyzed in the
      3 measurements, obtained from the cephalometric radiographies and the cast
      models, showed no statistical differences. The upper intermolar distance was
      57.20 +/- 2.60 mm; the lower intermolar, 55.16 +/- 2.40 mm; the upper
      interpremolar, 42.17 +/- 2.19 mm, and the lower interpremolar; 39.67 +/- 1.77 mm.
      On the posteroanterior cephalograms, the maxillary width was 65.97 +/- 3.42 mm
      and the mandibular width was 87.92 +/- 4.60 mm. There was intraresearcher and
      interresearcher correlation. There was no sexual dimorphism. The method proposed
      in this study can predict the transverse maxillary dimension, applying the
      formula ym = 8.62 + 0.88xm (ym = expected upper intermolar distance, xm = lower
      intermolar distance) for the molar region, and ypm = 4.87 + 0.94xpm (ypm =
      expected upper interpremolar distance, xpm = lower interpremolar distance) for
      the premolar region.

PMID- 19098535
TI  - Effects of iloprost on calvarial sutures.
AB  - Premature fusion of calvarial sutures is the result of a long and complex
      reaction, and several growth factors including transforming growth factor beta
      and basic fibroblast growth factor have important role in this event. Several
      prostaglandins have important functions in local bone modeling and remodeling by
      autocrine and paracrine mechanisms. Although effects of prostaglandins on long
      bones were studied both experimentally and clinically, there are limited data
      about cranial bones and sutures. In this study, we investigated the effect of
      iloprost-a stable prostacyclin analogue, which is widely used for the treatment
      of pulmonary arterial hypertension even in early pregnancy, to rat calvarial
      sutures. In 2 study groups, iloprost was injected intraperitoneally 10 and 15
      microg kg d, respectively. In the third group, dexamethasone 2 mg kg d + iloprost
      15 microg kg d was injected intraperitoneally to antagonize the effects of
      iloprost. In every group, 4 rats were killed at the postoperative 15, 30, and 45
      days, and specimens including the sagittal and frontal sutures were excised
      immediately. Routine histological and immunohistological staining were performed
      on the specimens. Morphological measurements were performed on the skulls, also.
      In histological evaluation, bone formation in the both frontal and sagittal
      suture area was increased and accelerated in iloprost groups. Dexamethasone
      inhibited the effects of iloprost on the third group. Expressions of transforming
      growth factor beta and basic fibroblast growth factor were also increased in
      immunohistological staining. In morphological measurements, statistically
      significant differences were found between control and study groups. Iloprost did
      not fused the rat calvarial sutures prematurely, but it narrowed the sagittal and
      frontal sutures especially after the second week of the study. This situation
      might effect the sutures of the babies of the pregnant patients with pulmonary
      arterial hypertension treated with iloprost. Cranial sutures, calvarial bones,
      and cranial shape of the babies of the pregnant patients who were treated with
      iloprost should be monitored to clarify the topic.

PMID- 19098536
TI  - Angular photogrammetric analysis of the soft tissue facial profile of Anatolian
      Turkish adults.
AB  - The purpose of this study was to establish norms of photogrammetric soft tissue
      profile analysis for Anatolian Turkish adults. Standardized right lateral facial
      photographs of 111 Anatolian Turks (64 females, 47 males) with class I skeletal
      pattern were taken. Age range was 21 to 40 years. Descriptive statistics for 8
      angular measurements were computed. Male and female values were compared with
      Mann-Whitney U test. Intraclass correlation coefficients (ICCs) were calculated
      for repeated measurements. Intraobserver reliability of the photogrammetric
      measurements was quite high with 6 measurements having ICCs above 95% and the
      other 2 measurements having ICCs of 77% and 87%. Sexual dimorphism was found for
      4 measurements: Nasofacial (G-Pog/N-Prn: P < 0.001) and middle facial height (N
      Trg_Sn: P < 0.05) angles were higher in men, whereas nasal (N-Prn-Sn: P < 0.01)
      and nasolabial (Cm-Sn-Ls: P < 0.05) angles were higher in women. Nasofrontal (G-N
      Prn), nasal (N-Prn-Sn), and nasolabial (Cm-Sn-Ls) angles revealed large
      individual variations.

PMID- 19098537
TI  - Parapharyngeal cyst: considerations on embryology, clinical evaluation, and
      surgical management.
AB  - Branchial cleft anomalies represent a common cause of cervical mass in adults.
      Describing a case report, we reviewed embryology, clinical elements, and
      treatment options for parapharyngeal congenital cysts. A case of a parapharyngeal
      cyst mimicking a tonsillar abscess is presented. A second branchial cleft cyst
      was hypothesized on a clinical and radiologic basis and then confirmed by
      histologic data. Magnetic resonance imaging provided fundamental information for
      the study of the parapharyngeal mass and its relationship with surrounding
      structures. In literature, surgical excision is the recommended therapy. We
      removed the cyst through a transcervical approach, with no complications or
      recurrence after 3 years. In our opinion, cervicotomy should be considered the
      gold standard approach, even for lesions not palpable in the cervical area. When
      dealing with a parapharyngeal cyst, second branchial cleft anomalies should be
      considered. Our experience confirms that cervicotomy is a safe approach to
      parapharyngeal congenital lesions.

PMID- 19098538
TI  - Rhinoplasty procedures: state of art in plastic surgery.
AB  - We have retrospectively assessed the charts of 166 patients who underwent
      rhinoplasties from March of 2005 to July of 2007, in the Plastic Surgery
      Department of the University of Torvergata Rome, Italy. From the operation chart
      of each patient, we filled out a form with the following details: access
      incisions to the nasal bone cartilage skeleton, maneuvers performed on the
      inferior lateral and superior cartilages, implants and/or grafts used, procedures
      made to the nasal base, types of osteotomies, and number of concomitant
      septoplasties. All the patients were operated under total anesthesia. The results
      were plotted on tables and graphs. In percentages, each surgical maneuver was
      separately analyzed, the need for grafts or incision in relation to the total
      number of patients operated, thus allowing for a numerical analysis of the
      approaches carried out in rhinoplasty procedures performed in our department.

PMID- 19098539
TI  - Three-dimensional cephalometric study of upper airway space in skeletal class II
      and III healthy patients.
AB  - Because the pharynx and the dentofacial structures have close relationship, a
      mutual interaction can be expected to occur between them. The literature presents
      skeletal malocclusion as etiology for airway morphology changes and/or vice
      versa. The present three-dimensional cephalometric study from computed tomography
      scans was carried out to investigate upper airway space in normal nasal breathing
      patients presenting skeletal pattern of classes II and III. In addition, the
      statistical analysis was done according to gender criterion. The results revealed
      that the majority of the airway measurements have not been affected by type of
      malocclusion. The three-dimensional technology used in this study also allowed
      the volume and surface area calculations, and no statistical significance was
      found. The retroglossal width and posterior nasal cavity height mean were larger
      in males than females in the class II group, but volume and cross-section area
      were not statistically significant. However, in class III group, although the
      differences in linear and angular measures means were not significant, the
      retropalatal volume and retroglossal volume and cross-section area were larger in
      males. The authors highlight that the evaluation of upper airway space should be
      an integral part of diagnosis and treatment planning to achieve functional
      balance and stability of the results.

PMID- 19098540
TI  - One-stage reconstruction of a defect of the oral commissure and of the cheek with
      a radial forearm free flap.
AB  - Several reconstructive methods have been proposed for complex clinical cases.
      These methods are based on composite graft tissue flaps which allow to obtain
      modest aesthetic-functional results. Only recently, revascularized flaps
      (fasciocutaneous free flap of radial) have been used. In this work, the authors
      present a clinical report of cheek mucosal carcinoma extended to the omolateral
      lip commissure, which has required the full thickness removal of the cheek, the
      lip commissure, and part of both lips; the use of a bileft free fasciocutaneous
      flap of radial (to reconstruct with a single flap both the cutaneous and mucosal
      deficits) has allowed for adequate reconstruction with good aesthetic and
      functional results.

PMID- 19098541
TI  - A repositioning technique for nasal fracture using the little finger.
AB  - A nasal bone fracture is usually repositioned using either Walsham or Asch
      forceps. However, accurate repositioning is often difficult. We therefore
      performed a repositioning technique using the little finger in 10 patients with a
      new nasal fracture. The results were satisfactory in all of the patients.
      Although medical experts may consider our method to be primitive, we believe that
      our method is both safe and effective, because the operator can recognize both
      the fractured part and its actual condition using the little finger. With this
      method, the occurrence of unnecessary new fractures can be prevented, in addition
      to minimizing the degree of mucosal damage and the occurrence of nasal
      hemorrhage. Furthermore, we consider that this technique can also reduce the
      occurrence of postoperative deformities due to the reduced mucosal contracture
      with this treatment modality. Even if the use of an instrument is deemed
      necessary, such as in treating saddle-nose-type fractures, initially feeling the
      fracture with the little finger will still allow for a more precise fracture
      reduction. We therefore consider our method to be both safe and effective at the
      initial stage of diagnosis and for the treatment of patients presenting with
      nasal bone fractures.

PMID- 19098542
TI  - Modified midfacial degloving approach for sinonasal tumors.
AB  - A perfect surgical approach to nasal cavity and paranasal sinus tumors should
      provide a broad exposition preserving the important structures with no cosmetic
      defect. Midfacial degloving (MD) technique provides good exposure without
      incisions and scars in the face. Classic MD technique includes rhinoplasty
      incisions. However, combination of the facial plastic skills of the rhinoplasty
      techniques with an oncologic approach limits its popularity. We modified the
      classic technique, which is performed without classic rhinoplasty incisions. The
      surgical approaches to 55 patients with benign and malignant sinonasal neoplasms
      are reviewed, and the modification of MD technique performed without rhinoplasty
      incisions is described. The study includes 41 male and 13 female patients with
      both benign and malignant sinonasal neoplasms. The ages of the patients were
      between 9 and 78 years with a mean age of 41.15 years. Follow-up of the patients
      ranged from 2 to 96 months with a mean of 31.7 months. Most of the cases were
      angiofibroma and inverted papilloma. Modified MD approach was used for all
      patients, and in 6 cases, the technique was combined with subcranial approach. We
      successfully resected the tumors in all of the patients. The most frequently
      encountered complaint in the postoperative period was temporary nasal crusting
      and epistaxis. An important complication was the rupture of subpetrous part of
      the internal carotid artery in one patient and also a temporary facial palsy in
      another one. Palatal dysfunction, oroantral fistula, or vestibular stenosis,
      which are significant complications of MD, were not observed in any of our cases.
      In this modified technique, rhinoplasty incisions are not used; therefore, the
      duration of operation is shortened, the technique becomes easier, and the
      incisions of the rhinoplasty procedure, which could cause circular stenosis, are
      avoided.

PMID- 19098543
TI  - Impact of microenvironment on the growth of primary human epidermal cells.
AB  - Although the conditions for in vitro cultivation of adult stem cells and tissue
      are easily standardized, little is known about the optimal conditions for
      biointegration after transfer of the tissue graft, playing an important role in
      the treatment of defects especially soft-tissue skin injuries. To examine the
      influence of the microenvironment, we investigated the doubling time of primary
      epithelial cells in relation to the culture medium. Serum from patients of
      different age groups (n = 15, <20 years; n = 9, >20 years; and fetal calf serum)
      was pooled independently of age and added to culture medium of epithelial cells
      from a skin donor (10%). Number of cells was counted in vitro after 1 and 4 days
      of cultivation using a photometric extinction test. Results were plotted using
      quotient for calculating cell proliferation ([T4 -T1]:T1). Statistical
      significance was calculated by Wilcoxon test. Highest proliferation rate was
      achieved by cultivating the cells in the heterological serum admixture.
      Homologous serum admixtures in the cell cultures of <20 donators yielded a
      significantly higher proliferation rate than adult serum (P < 0.01). High
      regenerative capacity of skin in children has, thus far, mainly been attributed
      to the high plasticity of the cellular structures. Our study shows for the first
      time that the age-dependent regenerative capacity in vitro is also influenced by
      age-dependent humoral factors. In vivo cells from older patients may thus be
      transferred into an altogether suboptimal microenvironment. Responsible humoral
      factors should be more closely examined to optimize the clinical management of
      cellular transplants.

PMID- 19098544
TI  - Three-dimensional temporomandibular joint modeling and animation.
AB  - The three-dimensional (3D) temporomandibular joint (TMJ) model derives from a
      study of the cranium by 3D virtual reality and mandibular function animation. The
      starting point of the project is high-fidelity digital acquisition of a human dry
      skull. The cooperation between the maxillofacial surgeon and the cartoonist
      enables the reconstruction of the fibroconnective components of the TMJ that are
      the keystone for comprehension of the anatomic and functional features of the
      mandible. The skeletal model is customized with the apposition of the
      temporomandibular ligament, the articular disk, the retrodiskal tissue, and the
      medial and the lateral ligament of the disk. The simulation of TMJ movement is
      the result of the integration of up-to-date data on the biomechanical
      restrictions. The 3D TMJ model is an easy-to-use application that may be run on a
      personal computer for the study of the TMJ and its biomechanics.

PMID- 19098545
TI  - Craniofacial fibrous dysplasia of orbit.
AB  - Fibrous dysplasia is a benign, rare, and idiopathic skeletal disorder
      characterized by replacement and expansion of medullary bone by disorganized
      fibro-osseous tissue. Treatment for these lesions is usually sought for cosmetic
      or functional reasons. The surgical approaches vary from watchful expectancy for
      the lesion to stop growing after puberty to conservative resection to radical
      resection. In this case reports, 3 patients with craniofacial fibrous dysplasia
      involving orbital region underwent surgery. In these primary cases, resection and
      immediate reconstruction were performed to regain facial contour, dental
      occlusion, and masticatory function. Significant improvement was seen in facial
      appearance, and all patients also felt that there had been improvement
      aesthetically. Therefore, conservative treatment for fibrous dysplasia, unless
      there is involvement of vital structure as orbital region, can be suggested.
      Early surgery to address progressive sensory disturbance is recommended so as to
      avoid the hazards of late-stage decompression.

PMID- 19098546
TI  - Primary malignant tumors of orofacial origin in Iran.
AB  - Orofacial malignant tumors are the sixth most common malignancy in the world and,
      with pharyngeal malignancies, the third most common one in the developing world.
      This study was carried out to determine the malignant oral primary tumors in
      Shiraz, southern Iran. From April 2002 to March 2007, all (181) malignant tumors
      of the orofacial region recorded in Fars Cancer Registry Center of Shiraz
      University of Medical Sciences in Shiraz, southern Iran, were enrolled. Age range
      of patients was 4 to 91 years (53.7 +/- 18.6 years), whereas 40% of cases were
      older than 60 years. Ninety percent were epithelial tumors, 6% sarcomas, and 4%
      lymphomas. The most common sites were tongue (34.3%) and major salivary glands
      (32.5%). Squamous cell carcinoma (50.8%) was the most common malignant orofacial
      tumor. Oral malignant tumors were more common in males than females with an older
      aged preponderance. The tongue was the most commonly affected site, and squamous
      cell carcinoma was the most common malignant orofacial tumor. There is an urgent
      need for a national program focusing on early detection of these tumors. Oral
      health professionals in Iran should be educated on oral cavity comprehensive
      examination because of the important role of dentists in early detection of
      malignant oral tumors.

PMID- 19098547
TI  - Prevention and treatment of penicillin-resistant Streptococcus pneumoniae
      meningitis after intracraniofacial surgery with distraction osteogenesis.
AB  - The prevalence of penicillin-resistant Streptococcus pneumoniae (PRSP) meningitis
      has increased worldwide, particularly in East Asia and the United States. We
      recently experienced a case of PRSP meningitis that developed during frontofacial
      distraction. The patient was a 7-year-old girl with Crouzon disease who was
      treated by frontofacial monobloc/Le Fort IV minus glabellar osteotomy with
      quadruple internal distraction devices. Penicillin-resistant Streptococcus
      pneumoniae meningitis was diagnosed after surgery and treated successfully with
      meropenem (a carbapenem) at 120 mg kg d every 8 hours, ceftriaxone (a third
      generation cephalosporin) at 100 mg kg d every 12 hours, and vancomycin (a
      glycopeptide) at 45 mg kg d every 6 hours. This case indicates that severe and
      fatal bacterial meningitis may occur as a postoperative complication due to
      multidrug-resistant bacteria indigenous to the nasal cavity after simultaneous
      osteotomy of the cranium and facial bone in intracraniofacial surgery, such as
      that for syndromic craniosynostosis and hypertelorbitism. In such cases,
      preventive strategies should include preoperative administration of pneumococcal
      vaccine, preoperative screening of nasal bacterial flora by nasal culture test,
      and prior administration of a carbapenem with good cerebrospinal fluid transfer
      or a third- or fourth-generation cephem covering PRSP. Postoperatively, suspected
      meningitis may be treated with a combination of the 3 drugs used in our case, in
      parallel with emergency cephalic contrast computed tomography and culture tests
      of blood and cerebrospinal fluid. Our experience suggests that these measures
      will facilitate a successful outcome in frontofacial distraction osteogenesis.

PMID- 19098548
TI  - Second primary cancer occurrence on forehead flap after reconstruction of nasal
      carcinoma.
AB  - We reported a case of basal cell carcinoma on the flap which was initially
      treated with excision of squamous cell carcinoma and forehead flap reconstruction
      of nasal dorsum. After 8 years of reconstruction, basal cell carcinoma was
      developed on the flap surface. This may be due to a recurrence, or a second
      primary tumor, or an activation of a dormant tumor with perturbing factors like
      surgery. In this report, our purpose was to discuss the possible
      etiopathogenesis, most appropriate diagnostic procedures, and treatment protocol
      for a carcinoma of the flap which has been used to reconstruct the previous
      cutaneous cancer.

PMID- 19098549
TI  - Inflammatory pseudotumor in the mandible.
AB  - Inflammatory pseudotumor (IPT) is a rare benign nonneoplastic lesion. The exact
      etiology of IPT remains unclear. Inflammatory pseudotumor in the maxillofacial
      region is exceptionally rare, and it is often mistaken for a malignancy. The
      diagnosis is still difficult and is based on the histological examination of the
      lesions composed of 3 types of inflammatory cells: histiocytes, plasma cells, and
      lymphocytes. Due to its feature mimicking invasive malignant tumors, we should
      consider this entity before we carry out radical procedures. In this short
      report, we will present a case of an aggressive IPT involving the mandible and a
      review of literatures.

PMID- 19098550
TI  - Hemimaxillofacial dysplasia: a variable presentation.
AB  - We report a case of hemimaxillofacial dysplasia followed in our clinic for 34
      years. A recent literature review has brought to our attention that the subject
      may have a variant of hemimaxillofacial dysplasia, but with some unique features.
      The reconstruction procedures are detailed, and long-term follow-up findings are
      described.

PMID- 19098551
TI  - Atypical lipomatous tumor in the submental region.
AB  - A 54-year-old male patient presented to our outpatient clinic complaining of a
      mass under his chin, which appeared nearly 1 year earlier. Pathologic diagnosis
      was atypical lipomatous tumor. To the best of our knowledge, this is the first
      reported case to localize subcutaneously in the head and neck region. Atypical
      lipomatous tumors/well-differentiated liposarcomas are rarely reported in the
      head and neck. We review the clinical and management features of atypical
      lipomatous tumors.

PMID- 19098552
TI  - Mycobacterium tuberculosis infection within parotid gland Warthin tumor.
AB  - Tuberculosis of the parotid gland is extremely unusual. Tuberculosis comprises
      2.5% to 10% of parotid gland lesions. Two clinical forms of parotid gland
      tuberculosis infection exist. One is a diffuse parenchymatous disease (either
      primary or secondary to nodal disease), resembling common infection. The second
      is a chronic, slow-growing, painless, and firm parotid mass mimicking a neoplasm.
      Most of these patients were diagnosed after parotid gland surgery and
      histopathologic evaluation. Warthin tumor is a well-known benign neoplasm of the
      salivary glands. It is the second most common tumor of the parotid gland.
      Mycobacterium tuberculosis within Warthin tumor is also unusual. Five cases with
      parotid gland tuberculosis within Warthin tumor were reported in the literature.
      In this report, we present a new patient with parotid gland tuberculosis within
      the Warthin tumor. This type parotid gland pathology is an extremely rare entity,
      and to the best of our knowledge, this is the second documented case using
      polymerase chain reaction. We also discussed the possible mechanisms of
      development of infection within Warthin tumor.

PMID- 19098553
TI  - Utilization of postcranioplasty skull molding caps in the treatment of Apert
      syndrome.
AB  - Patients with Apert syndrome have bilateral coronal craniosynostosis as one of
      their many distinguishing features. Surgical correction of this deformity is the
      mainstay of treatment. Abnormal widening of the skull base progresses despite
      cranioplasty. We describe a patient for whom a skull molding cap (SMC) was used
      after barrel-stave osteotomy and orbital rim advancement. This successfully
      restricted widening of her skull base while allowing growth in other dimensions.
      Utilization of skull molding caps after cranial surgery shows promise in this
      setting.

PMID- 19098554
TI  - Efficacy of distraction osteogenesis for mandibular reconstruction in previously
      irradiated areas: clinical experiences.
AB  - The efficacy of distraction osteogenesis in an irradiated area is controversial,
      although this procedure is now widely used in the field of craniomaxillofacial
      surgery. We report the clinical results from 4 patients with mandibular defects
      treated by lengthening of the irradiated mandibles. All patients had a mandibular
      defect caused by ablation of a malignant tumor. They had undergone radiotherapy
      at a total dose of 30 to 50 Gy to the surgical site after tumorectomy.
      Distraction osteogenesis was used as the secondary reconstruction method in 6
      sites of the remaining irradiated mandibles and in 1 site of the transferred
      vascularized scapula after radiotherapy. The transported segment was obtained by
      corticotomy with an initial gap of 0 to 2 mm, and internal extension plates were
      used. Distraction was commenced after a latency period of 7 to 10 days and
      performed at the rate of 0.25 to 1.0 mm/d. The total amount of distraction and
      consolidation periods ranged from 15 to 25 mm and 120 to 193 days, respectively.
      In 5 of the 6 sites in the remaining irradiated mandibles, satisfactory bone
      formation in the distraction gap was observed, although a fracture after new bone
      formation was observed in 1 site. Fibrous callus formation was observed in 1
      irradiated site only, and satisfactory results were obtained in another site of
      transferred vascularized scapula in the same patient. From these experiences, we
      believe that distraction may provide a reconstruction option for mandibular
      defects even under irradiated conditions because the procedure is simple and less
      invasive.

PMID- 19098555
TI  - Use of free tissue transfers in head and neck reconstruction.
AB  - More than 20 different free flaps have been described for head and neck
      reconstruction including fibula, iliac crest, scapula, radial forearm, rectus
      abdominis, anterolateral thigh, latissimus dorsi, and jejunum (Head Neck.
      2004;26:930). The high success rate and improved functional outcomes seen with
      free-tissue transfers have made them the workhorse for oromandibular defects
      (Plast Reconstr Surg. 2002;110:438; Microsurgery. 2004;24:374). In this article,
      we outline a few of the commonly used free flaps in head and neck reconstruction.

PMID- 19098556
TI  - Surgical management of temporomandibular joint ankylosis.
AB  - Ankylosis of the temporomandibular joint (TMJ) is one of the causes of persistent
      and progressive limitation of mouth opening. It usually requires to be corrected
      surgically; an intervention not without complications. This study was conducted
      in a central surgical hospital in Iraq (Baghdad) in the era hallmarked by
      shortage of nearly all facilities needed to accomplish solutions for a surgical
      task. The surgical procedure is displayed along with modifications,
      complications, and follow-up protocol. Fifteen patients (21 joints) have been
      treated surgically for TMJ ankylosis of different severities. All patients were
      treated at the Department of Oral and Maxillofacial Surgery, Specialized Surgical
      Hospital-Baghdad Medical City, Iraq. The study was carried out in the period
      between 1998 and 2002 (inclusive). Patients' ages ranged between 4 and 52 years.
      In addition to the clinical diagnoses, further evaluation of the ankylosis area
      was assisted by the use of orthopantomography and spiral computerized scanning
      (axial, coronal sections, and three-dimensional views). Maximal incisal opening
      was registered before and after surgery for further follow-up evaluation. Al
      Kayat and Bramely approach is advocated to expose the joint area. All 21 joints
      were operated through blind nasoendotracheal intubation general anesthesia.
      Computed tomography scans, wide exposures, aggressive resections, proper
      interposition materials, strict postoperative physiotherapy, and good family and
      patient compliance all may decrease the possibility of relapse and offer better
      results. Early management of TMJ ankylosis is important if more damage in
      orofacial structures and consolidation of bony union are to be avoided.

PMID- 19098558
TI  - Bifid nose with cleft hand deformity: syndromic association or undescribed
      anomaly?
AB  - The simultaneous presentation of bifid nose and bilateral cleft hand defects has
      not previously been described. Already rare in presentation, the bifid nose
      continues to challenge reconstructive surgeons as to optimal management. Although
      cleft defects of the hand may be somewhat more common, the multitude of surgical
      approaches available to correct these deformities is a testament to their lack of
      optimal effect. From an etiologic standpoint, it would seem that facial and hand
      clefting might share little in common. However, our recent experience with
      managing these coincident deformities in a newborn prompted a re-evaluation of
      material related to this exceedingly rare event. Here, we present a 4-month-old
      female infant with a coincident bifid nose and central ray deficiency.

PMID- 19098557
TI  - Clinicopathologic features of ameloblastoma in Kenya: a 10-year audit.
AB  - This study describes the clinical and pathologic features of ameloblastomas seen
      in the 2 main craniofacial treatment centers in Kenya in the 10-year period
      between January 1995 and December 2005. A total of 184 patient records were
      analyzed for this study. Eighty-two (44.6%) of the patients were male, and 102
      (55.4%) were female with an overall age range of 10 to 80 years (mean, 30.2
      years; SD, 14.1 years). There was no significant difference in gender
      presentation of ameloblastomas, although females presented at a slightly older
      age. The mean age for males was 29.9 years, and for females, it was 30.5 years.
      Patients generally tended to seek medical advice late, with the mean duration at
      first presentation of 46.3 months for males and 44.4 months for females. Most of
      the ameloblastomas (n = 172; 93.5%) were located in the mandible, 11 (6.0%) were
      in the maxilla, and 1 (0.5%) was in the soft tissues. Presenting symptoms
      included swelling (n = 182; 98.9%), pain (n = 64; 36.0%), mobile teeth/history of
      extraction (n = 104; 57.5%), purulent discharge (n = 39; 21.7%) and paresthesia
      (n = 10; 5.6%). The posterior mandible was the most commonly affected site,
      whereas maxillary ameloblastomas tended to occur in anterior sites. One hundred
      fifty-three ameloblastomas (83.2%) were of the solid/multicystic subtype; 8
      (5.3%) were unicystic; 1 (0.5%) was of extraosseous origin; 1 (0.5%) was
      desmoplastic; 9 (6.0%) were malignant, and 12 of the records had no
      histopathologic pattern specified.

PMID- 19098559
TI  - Primary cutaneous anaplastic large cell lymphoma of the face presenting as
      posttraumatic maxillary sinusitis.
AB  - Primary cutaneous anaplastic large cell lymphoma (ALCL) is an uncommon disease.
      It has various presentations that may mislead the diagnosis and cause delay of
      treatment. We report a 12-year-old boy who experienced persistent swollen and
      painful right cheek after blunt facial injury. The patient was first treated for
      maxillary sinusitis according to clinical history, but the pathology turned out
      to be primary cutaneous ALCL. Symptoms improved after chemotherapy with complete
      remission. No recurrence was noted during the follow-up period. The presentations
      of primary cutaneous ALCL of the face may mimic posttraumatic maxillary
      sinusitis. Any patient with facial prolonged symptoms or nonhealing wound should
      be excluded from this entity.

PMID- 19098560
TI  - Treacher Collins syndrome: an undescribed characteristic of the condition and its
      management with botulinum toxin and surgery.
AB  - Mandibulofacial dysostosis (Treacher Collins syndrome) is associated with
      clinical abnormalities of structures derived from the first and second branchial
      arches, including antimongoloid slant of palpebral fissures, colobomas of the
      lower eyelid, eyelash malformations, and malar and mandibular defects. We
      describe an unusual clinical feature associated with colobomas of the lower
      eyelids, in a patient with mandibulofacial dysostosis, successfully treated with
      botulinum toxin and subsequent surgery.

PMID- 19098561
TI  - Midface distraction without osteotomies in an infant with upper respiratory
      obstruction.
AB  - Midface hypoplasia is a common craniofacial anomaly and may manifest as part of a
      wider syndrome or as an isolated finding. Underlying this condition is a complex
      morphology, resulting from development across multiple interacting suture
      systems. Current treatment relies on various combinations of osteotomies and
      distraction using internal or external devices. Such procedures, while often
      successful, involve significant morbidity and trauma to the very young patients
      whom comprise the majority of the treatment group. The present article describes
      the successful development of a technique for midfacial distraction without
      osteotomies. In a case study representing a series of 11 patients, a 4-month-old
      baby girl with midface hypoplasia and respiratory obstruction requiring
      nasopharyngeal intubation underwent this 2-stage procedure. After 72-day
      distraction, upper incisor-posterior clinoid process distance had increased 18.4
      mm, and by 4 months after removal of the distraction devices, it had increased a
      further 2.6 mm. Craniofacial morphology was markedly improved combined with
      complete resolution of her respiratory obstruction. No blood transfusion or
      intensive care facility was required. This innovation demonstrates a procedure
      with similar efficacy but significantly reduced morbidity and cost compared with
      existing methods. Interestingly, continued growth after the distraction period
      may allude to a different mechanism of induced osteogenesis than previously
      described.

PMID- 19098562
TI  - Malignant eccrine spiradenoma of the scalp.
AB  - Malignant eccrine spiradenoma is a rare neoplasm generally arising from long
      standing benign eccrine spiradenomas; it is rarely seen on the scalp. A 27-year
      old woman with a malignant eccrine spiradenoma of the scalp, which had occurred 8
      months after the inadequate excision of a benign eccrine spiradenoma, was treated
      at our hospital. The patient underwent lymphoscintigraphy. A biopsy of the
      sentinel lymph nodes in the right periparotid and left occipital regions was
      performed, and the nodes showed no metastases. The tumor with its large
      subcutaneous extension and the outer table of the cranium were removed. A split
      thickness skin graft was applied on the exposed inner table. At 24 months' follow
      up, there has been no tumor recurrence. We report a case of a malignant eccrine
      spiradenoma of the scalp with cranial involvement that arose from an inadequately
      removed, long-standing, benign eccrine spiradenoma in a young patient. Also, we
      review the existing literature on malignant eccrine spiradenoma of the scalp.

PMID- 19098563
TI  - Lower facial contouring with botulinum toxin type A.
AB  - The use of botulinum toxin (BoNT) is well established in medical practice. The
      application of BoNT extends over many indications such as strabismus,
      blepharospasm, hemifacial spasm, and others. Another indication for the use of
      BoNT type A is the masseteric muscle hypertrophy to obtain a lower facial
      contouring. Authors report the treatment of 5 patients with intramuscular
      injection of BoNT. A high degree of patient and physician satisfaction was noted
      after the treatment. Authors concluded that BoNT type A can safely be considered
      as a noninvasive drug treatment for patients with MMH.

PMID- 19098564
TI  - Expression of transforming growth factor beta1 in ameloblastomas.
AB  - The aim of the present study was to compare the expression of transforming growth
      factor (TGF) beta1 in ameloblastomas (AMs) with different risk of recurrence by
      immunohistochemistry. A total of 29 cases of AMs were evaluated. The tumors were
      divided into 2 groups: group A (10 cases) composed of unicystic and peripheral
      AMs, associated with a low risk of recurrence, and group B (19 cases) composed of
      solid AMs, associated with a high risk of recurrence. Statistical evaluation
      showed significant differences between groups A and B lesions, with higher values
      of positivity for TGF-beta1 in stromal cells in group B tumors (P = 0.0308). No
      statistically significant differences of immunoreactivity were found in vessels
      and odontogenic epithelium between the 2 groups. The increased TGF-beta1
      expression in tumors with a high risk of recurrence could be explained with the
      fact that although TGF-beta acts as a potent tumor suppressor in the early stages
      of tumor progression, later it seems to enhance the invasive phenotype of the
      tumor.

PMID- 19098565
TI  - Lateral orbital expansion and gradual fronto-orbital advancement: an option to
      treat severe syndromic craniosynostosis.
AB  - In some patients with severe syndromic craniosynostosis, bony orbits are so small
      and shallow that the eyeballs dislocate. Dry cornitis and conjunctivitis can be
      seen often. When conventional fronto-orbital advancement is attempted in these
      cases, side walls of the orbit cannot go forward, because the width of bony orbit
      is smaller than the eyeball. To expand bony orbits and cranial volume,
      supralateral rim of the orbit was expanded laterally at the time of operation and
      gradually advanced foward postoperatively. With a coronal skin incision approach,
      frontal bone was taken off. Supralateral orbital rim bone was detached and cut at
      the centers of the orbits. Lateral expansion, 5 to 10 mm, was made and fixed with
      polylactate plates. A pair of distraction devices was fixed between the orbital
      rim and the temporal bone. Frontal bone was let floating on the dura mater and
      tied loosely with the orbital rim. Advancement of 1 to 1.5 mm/d was carried out,
      and the devices were taken off after 1-month consolidation period. Five patients
      with Pfeiffer syndrome, 1 with Crouzon, and 1 with Beare-Stevenson cutis gyrata
      syndrome were treated with this method. Procedure, outcomes, and complications
      are discussed.

PMID- 19098566
TI  - Cranial auto graft expansion (CAGE) technique for cranial vault expansion.
AB  - We present a method for cranial vault expansion that provides a strong construct,
      leaves small skull defects, and provides bony coverage of the sagittal sinus. The
      resultant small defects optimize the possibility for spontaneous reossification
      while avoiding large calvarial defects. This method has been used in 2 children
      who developed clinical evidence of total cranial growth restriction.

PMID- 19098567
TI  - The crooked nose: the use of medial iliac crest bone graft as a supporting
      framework.
AB  - The crooked nose is one that the vertical axis of the nose inclines from the
      midline. As a rule, a major septal deformity almost always accompanies to
      impairing breathing and aesthetic appearance. To achieve total straightening of
      the crooked nose, the septum must become the target of the treatment. To prevent
      redeviation, we used rigid bone grafts instead of flexible and relatively weak
      cartilage to maintain the support of the corrected deformity. Between February
      2005 and July 2007, 9 patients (all male) with crooked noses underwent corrective
      surgery. The mean age of the patients was 21 years (range, 19-23 years). The
      source of the bone graft was medial side of iliac crest in all patients. The mean
      follow-up was 18 months, ranging from 10 to 26 months. All patients had both
      functional and cosmetic problems. Mean operation time was 4 hours. Airway patency
      was improved in all cases. The grafts did not shift in any case and did not
      develop unsightly irregularities over time. Absorption of the grafts was not seen
      in the follow-up. There were no cases of extrusion or infection. No donor site
      complication occurred. None of the patient required secondary surgery. A residual
      deviation can be obvious despite all attempts, which has no deleterious effect on
      patient satisfaction. This article introduces a novel technique for the
      correction of the crooked nose.

PMID- 19098568
TI  - Auricular protection after ear surgery using a dust mask.
AB  - Resting and protection of wound surfaces after surgery are important in the
      promotion of wound healing. However, auricles protrude from the body surface, and
      there is hair in their surroundings. Therefore, postoperative dressing and
      protection require some modification. There are commercially available products
      for this purpose, but time is required for purchasing, and the cost is high for a
      product used only temporarily. In this study, we made a modification of simply
      using a dust mask for auricular protection after surgery, and we obtained
      relatively good results.

PMID- 19098569
TI  - Eye patch sandwich technique for stabilizing the intraoral skin graft to the
      cheek.
AB  - It is very important to secure skin graft in the defect of oral cavity. The tie
      over bolster technique is the most common method for securing intraoral skin
      grafts. However, gauze is the best material as a bolster that can easily
      accumulate saliva and debris and cause odor and discomfort to the patient. We
      describe an alternative technique to stabilize intraoral skin graft between 2
      aluminous eye patches and to readily keep the oral hygiene during the securing
      period.

PMID- 19098570
TI  - 7-plasty technique for the surgical treatment of congenital longitudinal ear lobe
      cleft.
AB  - The ear lobe plays an important part in the aesthetic appearance of the auricle.
      The clefts of the ear lobe may vary in a wide range of severity from a simple
      notching to extensive tissue deficiency. We have operated on a congenital
      longitudinal ear lobe cleft using an alternative surgical method and obtained a
      favorable result. This method consists of a 7-plasty (or inverted L-plasty) that
      was performed to correct the deformity. The inner edges of the lobes were
      excised, and a medial extension incision was added. This helped to drop the
      medial part inferiorly like a back-cut so that the length of that lobe was
      increased. Eversion of the lateral lobe was also done, and the edges were
      approximated so that the angle between the extension incision and the excision
      line was increased to produce an obtuse angle between the 2 lines. We report an
      alternative method of reconstruction that can be used in longitudinal ear lobe
      clefts that offers a favorable result.

PMID- 19098571
TI  - Dealing with the venous congestion of free flaps: venous catheterization.
AB  - For head and neck reconstruction after tumor ablation surgery, free flaps are
      mostly the chosen treatment modality for most of the centers. Coping with venous
      insufficiency and increasing venous outflow of the flap during this process
      increases the success rate. To increase venous outflow, triple-lumen central
      venous catheter is inserted to one of the donor veins of the flap that has venous
      insufficiency and one intact vein anastomosis.

PMID- 19098572
TI  - Use of an electrosurgical scalpel in gingival overgrowth associated with Rendu
      Osler-Weber syndrome.
AB  - We present a case of gingival overgrowth, with aesthetic repercussions,
      associated with Rendu-Osler-Weber syndrome. Treatment consisted of electric
      gingivectomy. We noted that it is necessary to carefully monitor hemorrhaging
      during surgery as well as to provide a correct differential diagnosis to
      distinguish this syndrome from other illnesses that involve gingival growth.

PMID- 19098573
TI  - Three minimally invasive procedures for removing lesions in the maxillary sinus.
AB  - We describe here 3 minimally invasive procedures for removing lesions from the
      maxillary sinus using an ultrathin endoscope, microscope, and
      otoscope.Preoperatively, a lesion in the maxillary sinus was identified by
      radiographic examination. Then the access hole position and advance direction of
      the endoscope and forceps were planned. Under local anesthesia, a small incision
      on the buccal mucosa was made in the planned position. The anterior bony wall of
      the sinus was exposed subperiosteally, and a small access hole for the insertion
      of an endoscope was made in the planned position and angled with a fissure bur.
      After identification of the lesion endoscopically, microscopically, or
      otoscopically, a forceps was inserted into the sinus cavity through the hole, and
      the lesion was seized and withdrawn from the sinus.The surgical procedures are
      suggested to be reliable, easy, and minimally invasive that provide a limited
      incision and bone removal and respect the integrity of the sinus.

PMID- 19098574
TI  - A novel approach for the reconstruction of medial canthal and nasal dorsal
      defects: frontal hairline island flap.
AB  - Medial canthal and dorsal nasal defects after surgery have been a challenging
      problem for surgeons and patients. The main purpose in reconstruction is not
      solely covering the defects with similar skin and soft tissue, but also causing
      minimal donor-area morbidity. The authors described an elliptical fashioned
      frontal island flap at the level of the frontal hairline, nourished by the
      vascular network composed of supraorbital and supratrochlear arteries, then
      carried subcutaneously to the defect area at medial canthus and upper nose. Any
      extra incisions above the eyebrow to control the pedicles were not necessary.
      Donor region was closed primarily; thus, scarring was hidden at the hairline. We
      present our frontal hairline island flap design and results in our series of 10
      patients.In our study, we aimed to reduce scarring at donor area by planning a
      forehead island flap in an elliptical fashion at the frontal hairline. There are
      no more incisions than the elliptical incision over the hairline. Primary closure
      of skin flaps at the donor ensures a final scar that is hidden at the frontal
      hairline border. Forehead hairline island flap is an important flap for small-
      and medium-size defects as an alternative to conventional paramedian forehead
      flap.

PMID- 19098575
TI  - Closed rhinoplasty with an intercartilaginous midmarginal incision.
AB  - In septorhinoplasty, one of the most critical points is to reestablish the
      support for the nasal tip damaged by surgery. This can be achieved by suturing
      the nasal structures to each other. We describe our incision and suturing
      technique for closed rhinoplasty, which provides wide exposure and adequate nasal
      tip support.

PMID- 19098576
TI  - One-stage skin grafting of the exposed skull with acellular human dermis
      (AlloDerm).
AB  - In cases of soft tissue defects in which the calvaria is exposed, the use of flap
      is generally considered. However, in cases in which patients' general status is
      poor or vascular insufficiency is present, the use of flap becomes difficult. A
      90-year-old male patient visited our outpatient clinic with a chief complaint of
      scalp defect accompanied by calvarial exposure after falling from an escalator.
      The patients' systemic status was poor, and the soft tissue defect was
      accompanied by calvarial exposure. Treatment involved removal of the outer table
      of the skull and application of acellular human dermis (AlloDerm). Then split
      thickness skin graft was performed in a single phase. This shortened the
      treatment period and produced excellent outcomes. Here, we report our case with a
      review of literatures.

PMID- 19098577
TI  - Multivectorial, external halo-assisted midface distraction in patients with
      severe hypoplasia.
AB  - Osteogenesis distraction is an increasingly used technique for the correction of
      facial deformities because it offers a faster and more controlled growth of the
      hypoplasic bone along with the elongation of the soft tissues. In this article,
      we describe the technique and our experience in midface distraction using an
      external multivectoral distraction device (BLUE Device; W. Lorenz, Jacksonville,
      FL) and custom-made midface osteotomies for the correction of severe hypoplasia.

PMID- 19098578
TI  - Transsphenoidal optic nerve decompression: an endoscopic anatomic study.
AB  - The objective was to study the relationships among the optic nerve, posterior
      paranasal sinuses, and ophthalmic artery. The identification of reliable anatomic
      landmarks would provide an endoscopic anatomic basis for optic nerve localization
      and effective prevention of ophthalmic artery injury during transsphenoidal optic
      nerve decompression surgery. The Messerklinger technique was performed to open
      the posterior ethmoid sinus and sphenoid sinus in 8 adult-head specimens. The
      opticocarotid recess and optic canal were identified under endoscopy, and the
      relationships between the optic nerve and posterior paranasal sinuses were
      observed. The relationship between the optic nerve and ophthalmic artery was
      examined. In all specimens, the opticocarotid recess could be identified;
      however, the optic nerve protuberance was present in only 10 sides (62%). Three
      types of relationships were found to exist among the optic nerve, sphenoid sinus,
      and posterior ethmoid sinus. The posterior ethmoid sinus was anterior and the
      sphenoid sinus was posterior in 8 sides (50%), the sphenoid sinus was both
      anterior and posterior in 5 sides (31%), and the ethmoid sinus was both anterior
      and posterior in 3 sides (19%). At the intracranial opening of the optic canal,
      the ophthalmic artery was inferomedial to the optic nerve in 9 sides (56%),
      inferior to the optic nerve in 4 sides (25%), and inferolateral to the optic
      nerve in 3 sides (19%). The ophthalmic artery coursed laterally from inferior to
      the optic nerve, and at the intraorbital opening of the optic canal, the
      ophthalmic artery was inferolateral to the optic nerve in 13 sides (81%) and
      inferior to the optic nerve in 3 sides (19%). The opticocarotid recess is always
      present; the imaging characteristics of endoscopy allow this recess to be more
      reliably identified than the optic nerve protuberance. It can be used as the
      anatomic landmark of choice in endoscopic optic nerve decompression. The origin
      of the ophthalmic artery is inferomedial to the optic nerve, and thereafter, it
      courses inferolaterally. An intersecting relationship exists along its course, a
      factor that must be taken into account during surgery to avoid injuring the
      ophthalmic artery.

PMID- 19098579
TI  - Cutaneous innervation of lower eyelid.
AB  - The loss of skin sensation or numbness after lower blepharoplasty is not
      uncommon. The aim of this study is to elucidate the infraorbital nerve (ION) and
      zygomaticofacial nerve (ZFN) in detail. Twenty-one hemifaces of 14 fresh Korean
      adult cadavers were dissected. Infraorbital nerve and ZFN came out of
      infraorbital foramen and zygomaticofacial foramen. They ran along superficial to
      the periosteum within and beneath the epimysium of the orbicularis oculi muscle
      and then through orbicularis oculi muscle perpendicularly and distributed to the
      skin. The distal branch approached to the lower border of the tarsal plate. Most
      terminal branches (93.8%) of ION were distributed medial to the lateral canthus.
      Only a few branches (6.2%) were lateral to the lateral canthus. Most (99.4%)
      terminal branches of ZFN were distributed lateral to the lateral canthus. Very
      few (0.6%) branches were medial to the lateral canthus. We conclude that the skin
      muscle flap infringes less than the skin flap on the terminal branches of ION and
      ZFN in exposure of the orbital floor as well as in lower blepharoplasty.

PMID- 19098580
TI  - Anatomical variations of nasal turbinates.
AB  - After the widespread use of endoscopic sinus surgery and paranasal sinus computed
      tomography, many variations of nasal turbinates have been described. In addition
      to the most common one-middle turbinate pneumatization (concha bullosa)-superior
      and inferior turbinate pneumatizations have also been described. Secondary and
      accessory middle turbinates that can mimic real middle turbinate are anomalies
      described in recent years. Paradoxical middle turbinate and bifid inferior
      turbinate are very rarely encountered anomalies and can be easily recognized in
      paranasal tomography but can be overlooked by endoscopical examination. In the
      present study, the computed tomography images of 384 patients were evaluated for
      nasal turbinate variations, as well as their relations to mucosal pathologies.
      The most frequent variation was found to be concha bullosa; the least frequent
      one was found to be bifid inferior turbinate. In 1 of our patients, 5 of the 6
      turbinates were found to have pneumatization, which is extremely rarely
      encountered in the literature. In this study, the prevalence of the variations of
      the turbinates and their association with chronic rhinosinusitis were
      investigated.

PMID- 19098581
TI  - Multiple huge epidermal inclusion cysts mistaken as neurofibromatosis.
AB  - Epidermal inclusion cyst is one of the common benign soft tissue tumors, and it
      can be easily confirmed and treated by surgical excision. We experienced a
      patient who had multiple masses on the face and scalp region, and the masses had
      been misdiagnosed as neurofibromatosis because of accompanying mental
      retardation. We would like to introduce a case of clinical diagnosis error caused
      by the lack of radiologic evaluation and pathologic confirmation. A 27-year-old
      male patient visited with multiple masses, with a length of approximately 1 to 10
      cm on the face and scalp region. These mass have developed since childhood
      without known etiology, and there has been no histologic examination or surgical
      excision done in the past. The patient's history of seizure disorder and mental
      retardation led the primary clinician to diagnose it as neurofibromatosis in the
      initial stage, and therefore, the clinician gave an advice on the possibility of
      frequent recurrence to the patient. As the masses increased in size, the patient
      came to our hospital after all. We found that the masses were soft and mobile
      through the physical examination, and magnetic resonance imaging showed evidence
      of epidermal inclusion cyst, which is distinguished from neurofibromatosis. Based
      on physical examination and magnetic resonance imaging, we performed total
      excision and biopsies. On the histologic examination, it was diagnosed as an
      epidermal inclusion cyst showing keratotic material internally, and the cyst wall
      was composed of lamellate keratin. The follow-up period was 12 months, and a
      recurrence has not occurred. The wound was healed without any specific
      complication, and both the patient and the guardian were satisfied with the
      physical enhancement. We have observed a misdiagnosed case that was misconceived
      by the situation, accompanying mental retardation. Due to this misconception, any
      surgical treatment was not performed at all, and the symptoms eventually worsened
      as multiple huge epidermal inclusion cysts. We present this case with a brief
      review of literature.

PMID- 19098582
TI  - Spontaneous involution of nasopharyngeal angiofibroma.
AB  - There are several studies addressing regression of residual nasopharyngeal
      angiofibroma after surgery, but spontaneous regression of this tumor has been
      reported in only 2 cases. We present a case of nasopharyngeal angiofibroma that
      has involuted spontaneously in the last 5 years. The tumor had been diagnosed at
      another institute. Computed tomography taken in 2002 had revealed the tumor
      occupying the entire sphenoid sinus and the pterygopalatine fossa, extending to
      the cavernous sinus and the infratemporal fossa on the right side. The
      vascularization of the tumor had been mainly from the internal maxillary artery
      on angiography. The internal maxillary artery had been occluded with a coil, but
      branches of internal carotid artery could not be embolized due to high risks of
      complications. In 2004 the patient was seen at our institute, and this time,
      repeated angiography revealed rich vascularization from the internal carotid
      artery. The patient did not accept any treatment and was put on follow-up. He had
      no complaint in January 2007. The tumor was seen to disappear completely, except
      a little remnant at the right pterygopalatine fossa on computed tomography. This
      is the third reported case in the literature with spontaneous regression of
      nasopharyngeal angiofibroma.

PMID- 19098583
TI  - Epithelial-myoepithelial carcinoma in minor salivary gland of the hard palate.
AB  - We present a case of 53-year-old man with an extremely rare malignant neoplasm,
      minor salivary gland epithelial-myoepithelial carcinoma of the hard palate. The
      lesion was detected incidentally by a dentist, and the patient was successfully
      treated with surgical excision and postoperative irradiation. The patient has
      remained asymptomatic and free of disease for 4 years after diagnosis.Minor
      salivary gland epithelial-myoepithelial carcinoma is an extremely rare and
      potentially aggressive tumor. The favorable outcome in the present case
      encourages the use of combined surgical excision and postoperative irradiation
      with curative intent.

PMID- 19098584
TI  - The unique simultaneous occurrence of a squamous cell carcinoma and a granular
      cell tumor of the tongue at the same site: a histological and immunohistochemical
      study.
AB  - We report a case of a 47-year-old man with a granular cell tumor (GCT) of the
      tongue colocalized with a squamous cell carcinoma. To our knowledge, this is the
      first case to be reported in the literature with such an association.
      Furthermore, we performed an immunohistochemical analysis with p63 to distinguish
      pseudoepitheliomatous hyperplasia from invasive squamous cell carcinoma.
      Clinicians and pathologists must be made aware of this potential diagnostic
      pitfall so that the workup of a tongue lesion does not end prematurely with a
      benign diagnosis of granular cell tumor with overlying pseudoepitheliomatous
      hyperplasia.

PMID- 19098585
TI  - Pott's puffy tumor.
AB  - Pott's Puffy tumor is a rare clinical entity characterized by subperiosteal
      abscess associated with osteomyelitis. It is usually seen as a complication of
      frontal sinusitis or trauma predominantly in the adolescent age group. Pott's
      Puffy tumor can be associated with cortical vein thrombosis, epidural abscess,
      subdural empyema, and brain abscess. The cause of vein thrombosis is explained by
      venous derange of the frontal sinus, which occurs through diplopic veins, which
      communicate with the dural venous plexus; septic thrombi can potentially evolve
      from foci within the frontal sinus and propagate through this venous system. An
      apparently healthy 7-year-old girl presented to the emergency service of
      otolaryngology with complaints of swelling of forehead and periorbital zone,
      headache, chills, fever, and rhinorrhea. The patient described in this case
      report had 2 important complications of paranasal sinus disease: the relatively
      common complication of postseptal cellulites and the less common complication of
      Pott's Puffy tumor.

PMID- 19098586
TI  - Pott's puffy tumor: multidetector computed tomography findings.
AB  - A subperiostal abscess of the frontal bone as a complication of osteomyelitis,
      appearing as a puffy, indolent tumor of the forehead, was first described by
      Pott. This less-common complication of is known as Pott's Puffy tumor. The
      complications of Pott's Puffy tumor are preseptal and orbital cellulites by
      downward spread to the orbit and intracranial infection by posterior extension.
      We present a case of Pott's Puffy tumor complicated by intracranial infection
      imaged by means of multidetector computed tomography.

PMID- 19098587
TI  - Epidemiology of squamous cell carcinoma of the oral cavity in Iran.
AB  - Squamous cell carcinoma accounts for approximately 90% of oral malignancies. This
      study was performed to determine the prevalence of oral squamous cell carcinoma
      (OSCC) in southern Iran in relation to sex, age, subsite distribution, and
      histologic differentiation of the tumor. Pathologic records of patients with a
      histologic diagnosis of OSCC at Fars Cancer Registry of Nemazee Hospital
      affiliated to Shiraz University of Medical Sciences during the period of April
      1992 through March 2007 were reviewed. Among 11,220 cases of cancer registered
      during this period, 200 cases were OSCC (1.7%). The age range of patients was 4
      to 87 years (mean, 56.9 years; SD, 15.5 years), with a 1.4:1 male-female ratio.
      Oral squamous cell carcinoma occurred more frequently in patients older than 60
      years. The tongue was the most commonly affected site (53%), followed by the
      buccal mucosa (9.5%) and maxillary gingiva (9%). The well-differentiated type
      (55.5%) was the most common, with the poorly differentiated OSCC being the least
      common (7.5%). The present study showed that OSCC was the most common malignancy
      in the tongue and buccal mucosa being more common in older age and male sex.

PMID- 19098588
TI  - Kimura disease.
AB  - Kimura disease (KD) is a chronic inflammatory disorder with unknown etiology,
      most commonly manifesting as painless unilateral cervical lymphadenopathy or
      subcutaneous masses in the head or neck region. Kimura disease is an unusual
      vascular tumor that typically occurs at 20 to 30 years of age, more commonly in
      women. There has been no documented case of malignant transformation; however,
      recurrence rates after excision may be as high as 25%. Surgery and medical
      therapy are useful for treatment. We present a 28-year-old man developed a
      unilateral cervical mass associated with KD. We made a complete excisional
      resection of the mass. We could not see any evidence of relapsing and decided
      that proper surgical resection of the lesion can be a treatment for KD. Because
      the disease can be seen with nephritic syndrome and has different treatment
      options, the otolaryngology specialist should consider KD in patients with neck
      mass and eosinophilia.

PMID- 19098589
TI  - Stabilization of a mobile premaxilla by cementing a bite splint with 1-stage
      bilateral alveolar bone grafting.
AB  - This study describes a method for stabilizing maxillary segments by performing
      bilateral alveolar bone grafting with an acrylic splint with a flat undersurface
      to reduce the occlusal pressure to the premaxilla. After premaxilla repositioning
      and bilateral alveolar bone grafting, the splint was attached to the maxillary
      teeth with glass ionomer cement. In 6 bilateral cleft cases, premaxilla
      repositioning and bilateral alveolar bone grafting were performed in 1-stage
      manner, and successful results were obtained. This easy and cost-effective
      procedure enabled rigid fixation of the insecure premaxilla with no complications
      during the treatment period.

PMID- 19098590
TI  - Invasion of the recurrent laryngeal nerve by tracheal tumor: an unusual
      presentation with coincidental huge multinodular goiter.
AB  - Vocal cord paralysis and goiter are 2 common problems encountered in
      otolaryngology practice. Their coexistence, however, should arouse suspicion of
      the presence of malignant thyroid disease. Primary tracheal cancer is uncommon,
      and its incidence is very low compared with laryngeal cancer. Primary tracheal
      tumors can cause recurrent nerve palsy. We report here a rare case of vocal cord
      paralysis caused by a clinically occult tracheal squamous cell carcinoma in an 80
      year-old patient with coincidental huge multinodular goiter.

PMID- 19098596
TI  - Atypical presentation of an intraorbital dermoid cyst.

PMID- 19098598
TI  - Inner border--a specific and significant colposcopic sign for moderate or severe
      dysplasia (cervical intraepithelial neoplasia 2 or 3).
AB  - OBJECTIVE: Investigation of the correlation between the colposcopic sign inner
      border and cervical intraepithelial neoplasia (CIN) 2 or 3 and its association
      with specific human papillomavirus (HPV) types and the age of the patient. STUDY
      DESIGN: Colpophotographs or cervicograms were taken from 947 women referred due
      to an abnormal cervical finding. Occurrence of the colposcopic sign inner border
      was evaluated retrospectively by 2 independent colposcopists. Histologic
      evaluation was based on punch or cone biopsies. Human papillomavirus testing was
      done using Hybrid Capture I or a polymerase chain reaction-based HPV test.
      RESULTS: The prevalence of the colposcopic phenomenon inner border in women with
      an atypical transformation zone was 7.6% (53/695). In 70% of women with inner
      border, CIN 2 or 3 was confirmed histologically. The sensitivity of the
      colposcopic sign inner border for detection of CIN 2 or 3 was 20%, and the
      specificity was 97%. In patients with inner border, the odds ratio for CIN 2 or 3
      was 7.7 (95% CI=4.2-14.3). There was no significant association between inner
      border and any high-risk HPV type. Cervical intraepithelial neoplasia 2 or 3
      associated with inner border was significantly more frequent in patients younger
      than 35 years. CONCLUSION: Inner border is a rare colposcopic phenomenon but
      highly specific for CIN 2 or 3 in young women.

PMID- 19098599
TI  - The diagnostic accuracy of colposcopy in previously treated cervical
      intraepithelial neoplasia.
AB  - OBJECTIVE: To determine whether colposcopy is reliable in diagnosing cervical
      intraepithelial neoplasia in women who have undergone a previous cervical
      excision biopsy. MATERIALS AND METHODS: A prospective study of women attending
      the colposcopy clinic at the University Hospital of North Staffordshire was
      performed between January 1998 and December 1999. RESULTS: A clear histological
      diagnosis of the grade of cervical intraepithelial neoplasia was available for
      469 in the treatment-naive group and 58 in the treatment group. kappa
      coefficients comparing the colposcopic impression (negative, low-grade, high
      grade, or invasion) with histological diagnosis showed that there was no
      difference between the treatment-naive group, weighted kappa=0.46, and the
      previous treatment group, weighted kappa=0.47. The sensitivity, specificity,
      positive predictive value, and negative predictive value of colposcopy for any
      cervical disease in the treatment-naive women were 93.9%, 51.9%, 96.7%, and
      34.1%, respectively, compared with 77.6%, 66.7%, 86.4%, and 35.3% in previously
      treated women. The sensitivity of colposcopy fell when it was used to
      differentiate normal and low-grade disease from high-grade disease and invasion:
      82.4%, 55.9%, 82.6%, and 49.6% for treatment-naive women, compared with 61.5%,
      84.2%, 60.0% and 51.6%, respectively, for the previous treatment group.
      CONCLUSIONS: Previous treatment to the cervix does not seem to impair the ability
      of colposcopy to differentiate normal cervix from all grades of cervical
      abnormality in women where the squamocolumnar junction is visible. However, there
      is a suggestion that the sensitivity of colposcopy to differentiate negative/low
      grade disease from high-grade disease/invasion is lower in previously treated
      women.

PMID- 19098601
TI  - The colposcopic feature ridge sign is associated with the presence of cervical
      intraepithelial neoplasia 2/3 and human papillomavirus 16 in young women.
AB  - OBJECTIVE: Interobserver and intraobserver correlation between the colposcopic
      phenomenon ridge sign and its association with cervical intraepithelial neoplasia
      (CIN) 2 or 3, with a specific human papillomavirus (HPV) type, and with the age
      of the patient. STUDY DESIGN: Colpophotographs, cervical smears, and histologic
      results of punch or cone biopsies of 592 patients were evaluated.
      Colpophotographs were analyzed retrospectively for the presence or absence of an
      opaque acetowhite ridge at the squamocolumnar junction (ridge sign) by 3
      gynecologists of different experience. RESULTS: Interobserver reliability for
      colposcopic grading of CIN was between 18.2% and 82.3%. Concerning the ridge
      sign, interobserver agreement varied between 25.3% and 49.4% according to the
      observers' experience, and intraobserver reliability varied between 56.4% and
      67.5% (Cohen kappa=0.310-0.469). In 83 (14.0%) of 592 patients, a ridge sign was
      diagnosed by the most experienced investigator. Cervical intraepithelial
      neoplasia 2 or 3 was confirmed histologically in 53 of these 83 women (63.8%).
      Sensitivity of ridge sign for detection of CIN 2 or 3 was 33.1%; specificity was
      93.1%. Women with ridge sign were significantly younger than women with no ridge
      sign (p< .001). Ridge sign was associated with the presence of HPV 16 (p< .001).
      CONCLUSION: Ridge sign is a highly specific marker for CIN 2 or 3 and associated
      with HPV 16 and young age.

PMID- 19098600
TI  - Interpretability of excisional biopsies of the cervix: cone biopsy and loop
      excision.
AB  - OBJECTIVE: To compare the results of cold knife conization (CKC) and loop
      electrosurgical excision procedure (LEEP) for cervical intraepithelial neoplasia
      to determine if excisional method has effects on pathologic interpretation.
      METHODS: Retrospective review of the perioperative medical records of patients
      who had a CKC and electrosurgical loop excision of cervix. Patients selected had
      either primary treatment for cervical intraepithelial neoplasia, suspected
      invasion, glandular abnormalities or discordant cytology. RESULTS: Among the
      eligible patients, 61 had CKC and 96 had LEEP. Overall, CKC specimens had
      interpretable surgical margins more frequently than LEEP (95% vs 85%); however,
      it was not statistically significant (p=.1). Margins were less likely to be
      involved with neoplasia in CKC specimens (16% vs 38%; p=.005). Loop
      electrosurgical excision procedure specimens were less likely to yield a single
      intact specimen (1.1 vs 1.9; p=.000). Logistic regression showed a significant
      effect of specimen number (p=.04) on interpretability. CONCLUSION: Current
      American Society for Colposcopy and Cervical Pathology (ASCCP) guidelines for
      diagnostic excisional procedure used for glandular lesions suggest that the
      procedure provides "an intact specimen with interpretable margins." Loop
      electrosurgical excision procedure in the current study was associated with an
      increased number of specimens that limited interpretability and an increased
      number of positive margins. Cold knife conization is preferred in cases where
      margin status is critical, such as glandular lesions and suspected microinvasion.
      If LEEP is performed, clinicians should attempt to obtain a single surgical
      specimen maximizing the pathologic interpretation and disease-free margins.

PMID- 19098602
TI  - Access of Black, Hispanic, and nonprivately insured women to liquid-based
      cytology, human papillomavirus DNA testing, and on-site colposcopy in the United
      States.
AB  - OBJECTIVE: To determine whether patient race, ethnicity, or insurance status was
      associated with access to cervical cancer screening with liquid-based cytology
      (LBC) and with human papillomavirus (HPV) DNA testing and with access to on-site
      colposcopy at the provider's principal practice site. MATERIALS AND METHODS: We
      conducted a nationally representative survey of clinicians in specialties that
      provide cervical cancer screening. Adjusted odds ratios (OR) were estimated for
      the associations between race, ethnicity, and insurance status of patients and
      provider use of LBC, HPV DNA testing, and on-site colposcopy. RESULTS: Providers
      who cared for >or=20% Hispanic patients were less likely to use LBC (OR 0.60, 95%
      CI=0.42-0.84). Providers who cared for >or=25% black women (OR 0.71, 95% CI=0.51
      0.98) and providers who cared for <75% privately insured patients (OR 0.66, 95%
      CI=0.46-0.95) were less likely to use HPV DNA testing. Providers who cared for
      <75% privately insured patients were less likely to have on-site colposcopy (OR
      0.57, 95% CI=0.37-0.89), but those who cared for >or=20% Medicaid patients were
      more likely to have on-site colposcopy (OR 1.86, 95% CI=1.26-2.73). CONCLUSIONS:
      Given the high rates of cervical cancer in minority women, access to cervical
      cancer screening and diagnostic follow-up must be ensured. It may also be
      beneficial to ensure affordable access to technologies such HPV DNA testing that
      increases the sensitivity of disease detection and to on-site colposcopy that
      facilitates follow-up of abnormal cytology.

PMID- 19098603
TI  - Oncogenic human papillomavirus testing in an adolescent population with atypical
      squamous cells of undetermined significance.
AB  - OBJECTIVE: The American Society for Colposcopy and Cervical Pathology 2006
      consensus guidelines state that oncogenic human papillomavirus (HPV) DNA testing
      is unacceptable for patients 20 years and younger with atypical squamous cells of
      undetermined significance (ASC-US). The objective of this study is to determine
      the HPV frequency in ASC-US patients 20 years and younger and to investigate
      subsequent colposcopic diagnoses. MATERIALS AND METHODS: Cytopathology records at
      the University of Florida/Shands-UF were reviewed from March 2003 to June 2007 to
      identify patients 20 years and younger with ASC-US on screening Pap tests. Human
      papillomavirus test results and subsequent colposcopic diagnoses were recorded.
      RESULTS: A total of 333 patients were identified. Seventy-five were not HPV
      tested. Of the remaining 258, 127 (49%) were negative(-) for HPV, whereas 131
      (51%) were HPV positive(+).In the HPV(-) population (n=127), 3 (2%) patients were
      referred for colposcopy and had benign findings. In the HPV(+) population
      (n=131), 48 (37%) patients were referred for colposcopy. Of these 48, 25 had
      benign colposcopic findings, 12 had cervical intraepithelial neoplasia 1 (CIN 1),
      and 11 had CIN 2/3. No invasive disease was identified. Nine of the 11 patients
      with CIN 2/3 were 18 years and older. CONCLUSIONS: In our institution, 51% of ASC
      US patients 20 years and younger were HPV(+). Colposcopy with subsequent
      histological diagnosis, available on 48 patients, demonstrated 11 (23%) of the
      HPV(+) group to have CIN 2/3. The American Society for Colposcopy and Cervical
      Pathology guidelines recommend observation (via repeat colposcopy and cytology)
      for adolescents with CIN 2 and treatment (via excision or ablation) for CIN 3.
      Human papillomavirus testing ASC-US adolescents in our institution may be
      "acceptable."

PMID- 19098604
TI  - Value of normal colposcopy after an abnormal cervical smear report.
AB  - BACKGROUND: Colposcopy is a secondary screening test used after a cytological
      specimen is reported as abnormal. A negative or normal colposcopy is not an
      infrequent outcome, and clinicians need to be aware of the clinical value of a
      normal and satisfactory colposcopic assessment.To address this problem, the
      underlying causes need to be fully understood. To this end, we have analyzed a
      retrospective dataset relating to new referrals to an urban colposcopy service.
      METHOD: We have reviewed 1,927 consecutive new colposcopic attendances during a 4
      year period (1996-2000). Of these cases, 1,589 (82.4%) had documented
      satisfactory colposcopy in that the whole transformation zone was identified, and
      any lesion seen within it was suitable for outpatient-directed biopsy. These
      cases form the basis of this dataset. Seven hundred seventy-one colposcopies were
      classified as normal (48%). RESULTS: The presenting smear was atypical squamous
      cells of undetermined significance (ASCUS) (41.3%), high-grade squamous
      intraepithelial lesion (HiSIL) (42.2%), low-grade squamous intraepithelial lesion
      (LoSIL) (13.1%), and unsatisfactory in 3.4%. One hundred five patients (13.6%)
      eventually underwent loop diathermy excision (loop electrocautery excision
      procedure). The indications to treat were as follows: a high-grade smear (N=31;
      29.5%), a colposcopic suspicion of any cervical intraepithelial neoplasia in the
      presence of any smear result (N=35; 33%), or a persisting minor cytological
      abnormality (N=39; 37%). Patients were treated either at their first visit if
      they had a high-grade smear or up to the 10th visit. Forty-eight (45%) of the
      treated patients had high-grade disease. No cases of invasive disease were
      recorded. CONCLUSION: Normal colposcopy in the presence of a low-grade cervical
      smear is associated with a very low risk of having or developing high-grade
      disease. The negative predictive value of normal colposcopy is a valuable
      clinical utility and underpins the importance of appropriate colposcopic training
      and the development of competencies that enable the confident exclusion of
      dysplasia.

PMID- 19098605
TI  - Epidemiology and costs of screening and management of precancerous lesions of the
      cervix in Spain.
AB  - OBJECTIVE: Oncogenic human papillomaviruses (HPVs) are essential causes of
      cervical cancer. Screening prevents cancer by detecting precancerous lesions
      (cervical intraepithelial neoplasia, CIN). Our aim was to assess the annual
      number of Pap smears and CIN diagnoses in Spain and to estimate associated
      management costs. MATERIALS AND METHODS: A 1-year retrospective cross-sectional
      study was conducted among 65 gynecologists from public primary health care
      centers in 6 autonomous regions in Spain. We documented the total number of Pap
      smears performed and the management of women with CIN. Data on health care
      resource use related to CIN management for 2 years after diagnosis were collected
      and combined with unit costs to assess the mean cost per patient. We extrapolated
      to the general female Spanish population to estimate the total cost of screening
      and CIN management from the third-party payer's perspective. RESULTS: In our
      study sample, 3.5% of routine Pap smears were abnormal. We estimated that 7.6
      million Pap smears are performed annually in Spain, at a cost of 622 million euro
      (US$987). Furthermore, 40,530 women are annually diagnosed with CIN 1, 26,243
      with CIN 2, and 28,423 with CIN 3. The mean cost of CIN management per patient
      was 1,115 euro for CIN 1, 1,626 euro for CIN 2, and 2,090 euro for CIN 3. The
      total cost of CIN management was estimated at 147 million euro (US$233).
      CONCLUSIONS: This study shows that the costs of screening and management of CIN
      represent a heavy burden to the public health system in Spain.

PMID- 19098606
TI  - Aggressive angiomyxoma of the vulva: a case report and review of the literature.
AB  - BACKGROUND: Aggressive angiomyxoma is a variant of myxoid neoplasms of the female
      pelvic soft parts. The term "aggressive" refers to the tumor's locally
      infiltrative and recurrent nature because distant metastases are rare. CASE: A 25
      year-old woman presented with a 9-month history of an asymptomatic, polypoid mass
      arising from the right anterior labium minus. Histopathological and radiological
      examinations were consistent with a diagnosis of aggressive angiomyxoma. The
      patient was treated with a GnRH agonist followed by surgical excision.
      CONCLUSION: We highlight the novel use of a GnRH agonist as a neoadjuvant to
      surgery in aggressive angiomyxoma to shrink the tumor preoperatively and decrease
      surgical morbidity.

PMID- 19098607
TI  - Differential diagnosis of seizure associated with topical lidocaine in a patient
      with vestibulodynia.

PMID- 19098608
TI  - Home study course: winter 2009. A 27-year-old, G5 P3013, presents to the clinic
      for prenatal care at 20 weeks.

PMID- 19098617
TI  - Glycemia management in neurocritical care patients: a review.
AB  - Intensive research investigating the relation between the management of glycemia
      and outcome in patients receiving neurocritical care has underlined the possible
      benefits and adverse events related to glucose control. Here, we review
      experimental and clinical studies investigating the effects of hypoglycemia and
      hyperglycemia on the brain that advance current knowledge on managing glycemia in
      patients receiving neurocritical care.

PMID- 19098618
TI  - Bispectral index-guided administration of anesthesia for transsphenoidal
      resection of pituitary tumors: a comparison of 3 anesthetic techniques.
AB  - The main aims of anesthesia for pituitary surgery include maintenance of
      hemodynamic stability, provision of conditions that facilitate surgical exposure,
      and a smooth emergence to facilitate a prompt neurologic assessment. The primary
      aim of our study was to compare the effects of 3 anesthetic regimens on
      hemodynamics and recovery characteristics of the patients. Ninety patients
      undergoing transsphenoidal surgery were enrolled in the study. Standard
      anesthesia technique was followed for induction. Patients were randomly divided
      to receive propofol, isoflurane, or sevoflurane for maintenance of anesthesia.
      The bispectral index target range during maintenance was 40 to 60. The
      hemodynamic variables (heart rate and mean arterial pressure) and bispectral
      index were noted during the various stages of the surgery. The time to emergence
      and extubation was noted. We evaluated cognitive function at 5 and 10 minutes
      posttracheal extubation. The 3 study groups were comparable with respect to age,
      sex, weight, and duration of surgery. We observed an increase in heart rate and
      blood pressure during intubation, nasal packing, and insertion of self-retaining
      nasal speculum. After tracheal intubation, the rise in blood pressure was more in
      sevoflurane group than propofol. During emergence, hypertensive response was seen
      in all patients. Emergence and extubation times were significantly shorter with
      propofol and sevoflurane. Patients who received propofol had better cognition
      scores. Aldrete scores were better with propofol and sevoflurane than isoflurane.
      The pressor response after intubation and emergence hypertension was
      significantly less with propofol. Better recovery profile was seen in sevoflurane
      and propofol groups and a better cognition in patients receiving propofol.
      Propofol plus nitrous oxide anesthesia could be the technique of choice in
      patients undergoing transnasal transsphenoidal pituitary surgery.

PMID- 19098619
TI  - Optic nerve ultrasound for detection of intracranial hypertension in intracranial
      hemorrhage patients: confirmation of previous findings in a different patient
      population.
AB  - Bedside ultrasonographic measurement of optic nerve sheath diameter (ONSD) has
      been proposed as a method to detect raised intracranial pressure (ICP) in various
      clinical settings. The aim of our study is to evaluate the use of ultrasonography
      in the case of intracranial hemorrhage and to assess the validity of the
      conventional cut-off point of 5 mm. A prospective blind observational study in a
      10-bed multivalent intensive care unit was carried out by enrolling 53 adult
      patients with primary intracerebral hemorrhage (23) or subarachnoid hemorrhage
      (30), requiring ICP monitoring, sedation, and mechanical ventilation and 53
      control patients with no intracranial pathology, requiring sedation and
      mechanical ventilation. ONSD was measured 3 mm behind the globe by using a 7.5
      MHz linear ultrasound probe. Mean binocular ONSD was used for data analysis.
      Nineteen patients proved to have raised ICP (>20 mm Hg). In this group, ONSD at
      admission was 6.2+/-0.6 mm, a significantly higher value than in low ICP patients
      (P<0.01). In the 34 patients with ICP <20 mm Hg, ONSD was 5.0+/-0.5 mm, and it
      resulted not significantly different from ONSD in the control group (4.9+/-0.4
      mm). A receiver operator characteristic curve was constructed and an ONSD
      threshold of 5.2 mm as a predictor of ICP >20 mm Hg proved to be an attractive
      combination of sensitivity and specificity (94% and 76%, respectively). In
      conclusion, our study confirms the utility of optic nerve ultrasound in the early
      diagnostic evaluation of patients with known or suspected intracranial
      hemorrhage.

PMID- 19098620
TI  - In-hospital complications and mortality after elective spinal fusion surgery in
      the united states: a study of the nationwide inpatient sample from 2001 to 2005.
AB  - Spinal fusion surgery has increased dramatically and patients presenting for
      surgery are often more medically challenging. We hypothesized that advanced age
      and coexisting morbidities have increased in the population undergoing spinal
      fusion and are associated with greater risks for immediate complications and
      mortality. The Nationwide Inpatient Sample was retrospectively reviewed for
      discharges after a principal procedure code for elective spinal fusion. Total
      records meeting study inclusion criteria were 254,640. Coexisting morbidities
      were tabulated using Elixhauser comorbidities and the Charlson comorbidity index.
      Logistic regression identified risk factors associated with in-hospital mortality
      and early complications. The largest increase in spinal fusion surgery was in
      patients >65 years. Overall, those with at least 1 comorbidity increased (49% to
      62%; P=0.002), as did mean Charlson index (0.146 to 0.202; P<0.001). In-hospital
      mortality was 0.13%, but 0.29%, and 0.64% for patients of 65 to 74, and those
      >or=75 years, respectively. Adjusted odds ratios for complications in 65-year to
      74-year olds versus <65 years was 1.78 (95% confidence interval, 1.71-1.84;
      P<0.001), and for mortality 3.81 (95% confidence interval, 2.62-5.55; P<0.001);
      risks increased with the number of coexisting morbidities. Congestive heart
      failure, chronic pulmonary disease, coagulopathy, metastatic cancer, renal
      failure, and weight loss significantly correlated with in-hospital mortality,
      whereas hypertension or hypothyroidism had, unexpectedly, the opposite effect.
      Although it is known for some other forms of complex surgery, we showed that
      elderly and medically complex spinal fusion patients were at increased risk for
      in-hospital mortality and early complications. The majority of complications were
      operative, pulmonary, cardiovascular, or genito-urinary. Patient risk correlated
      with the number and nature of coexisting morbidities.

PMID- 19098621
TI  - Fructose-1,6-bisphosphate and fructose-2,6-bisphosphate do not influence brain
      carbohydrate or high-energy phosphate metabolism in a rat model of forebrain
      ischemia.
AB  - Phosphorylated fructose compounds have been reported to lessen neuronal injury in
      in vitro models of hypoxia and in vivo models of ischemia. Although a variety of
      mechanisms have been proposed to account for this finding, it is unknown if
      intracellular uptake and incorporation of these compounds into the glycolytic
      pathway contribute to the benefit. We evaluated phosphorylated fructose
      administration in an adult rat model of transient, near-complete cerebral
      ischemia to determine its impact on brain metabolism before, during, and after
      ischemia. Fifty-four pentobarbital anesthetized rats were randomly assigned to
      receive IV infusions of either fructose-1,6-bisphosphate, fructose-2,6
      bisphosphate, or 0.9% saline. After 2 hours of infusion, 18 rats (6/treatment
      group) were subjected to brain harvesting before any ischemia, 18 additional rats
      had brain harvesting at the completion of 10 minutes of forebrain ischemia (2
      vessel occlusion plus induced hypotension), and 18 rats had harvesting after
      ischemia and 15 minutes of reperfusion. Cortical brain samples were analyzed for
      ATP, ADP, AMP, phosphocreatine, glucose, and glycogen. When compared with
      placebo, neither phosphorylated fructose compound altered preischemic,
      intraischemic, or postischemic concentrations of brain high-energy phosphates,
      glucose, glycogen, or lactate, nor did they influence the intraischemic
      metabolism of endogenous brain glucose or glycogen. On the basis of these
      results, we conclude that mechanisms other than augmented carbohydrate metabolism
      are responsible for previous reports of neuronal protection by the
      bisphosphonates.

PMID- 19098622
TI  - The direct effects of propofol on pial microvessels in rabbits.
AB  - Propofol is widely used for neurosurgical anesthesia; however, its effects on the
      pial microvasculature are unknown. We therefore evaluated the direct effects of
      propofol on pial microvessels in rabbits. Pial microcirculation was visualized
      using a closed cranial window technique in 20 Japanese white rabbits. In the
      first experiment (n=14), after baseline hemodynamic measurements, the cranial
      window was superfused with 5 increasing concentrations of propofol (10, 10, 10,
      10, 10 mol/L; n=8) or intralipid (at comparable concentrations; n=6) dissolved in
      artificial cerebrospinal fluid for 7 minutes each. A typical anesthetic
      concentration of 5 microg/mL corresponds to 10 mol/L. In the second experiment
      (n=6), phenylephrine 10 mol/L and nitroglycerin 10 mol/L were applied topically
      for 7 minutes under pentobarbital anesthesia. In the third experiment (n=3),
      electroencephalogram and bispectral index were measured under pentobarbital
      anesthesia. Diameters of selected pial arterioles and venules were visualized
      with a microscope-video capture unit combination and subsequently measured with a
      digital video analyzer. Topical application of propofol at 10, 10, 10, or 10
      mol/L did not alter the diameters of the pial microvessels; however, at 10 mol/L
      propofol induced dilation in large and small arterioles, along with venular
      dilation. Intralipid alone did not have any significant effect on vessel
      diameters. Phenylephrine and nitroglycerin produced pial arteriolar and venular
      constriction and dilation, respectively. Phenylephrine constricted and
      nitroglycerin dilated pial arterioles and venules. Pentobarbital did not produce
      either burst suppression or an isoelectric electroencephalogram. The results
      confirm our hypothesis: clinically relevant concentrations of propofol, that is,
      approximately 10 mol/L, do not dilate pial arterioles or venules.

PMID- 19098623
TI  - Changes of endothelin and calcitonin gene-related peptide concentrations in
      plasma during propofol anesthesia.
AB  - We had previously reported that plasma concentrations of endothelin (ET)
      decreased significantly in the operating room during desflurane anesthesia. The
      purpose of the present study was to explore whether changes in plasma ET and
      calcitonin gene-related peptide (CGRP) concentrations were altered during
      propofol anesthesia in patients undergoing clipping of an intracranial aneurysm.
      Forty-five patients scheduled for selective craniotomy and aneurysm clipping were
      anesthetized with propofol. A catheter was inserted into the radial artery for
      blood sampling before anesthesia. Serial plasma concentrations of ET and CGRP
      were determined before induction, after dura incision, after clipping of the
      aneurysm, and 30 minutes after clipping. ET concentrations in the plasma
      increased significantly after clipping of the aneurysm compared with
      concentrations after dura incision. However, no significant changes in ET levels
      were found after anesthesia. Plasma concentrations of CGRP decreased
      significantly during anesthesia. This evidence suggests that direct stimulation
      of the intracalvarium blood vessel before aneurysm clipping may increase ET;
      however, propofol did not decrease ET, in contrast with our previously reported
      findings for desflurane anesthesia. Considering the well-recognized vasodilatory
      effect of CGRP, it is possible that a decrease in the plasma concentration of
      CGRP plays a role in the pathogenesis of cerebral vasospasm, which is often seen
      postoperatively.

PMID- 19098625
TI  - Pro: Tight control of blood glucose in the brain-injured patient is important and
      desirable.

PMID- 19098626
TI  - Con: Tight glucose control after brain injury is unproven and unsafe.

PMID- 19098629
TI  - Anesthetic management of a patient with rotor syndrome for cerebral aneurysm
      clipping.

PMID- 19098630
TI  - LMA and ventriculo-peritoneal shunt surgery: is it the ideal airway?

PMID- 19098631
TI  - Concomitant factors leading to neurogenic pulmonary edema development.

PMID- 19098632
TI  - Prevention of airway injury during spine surgery: rethinking bite blocks.

PMID- 19098633
TI  - Treatment regimen in patients with neurogenic pulmonary edema after subarachnoid
      hemorrhage.

PMID- 19098634
TI  - Airway management technique for vascular mass in the oral cavity.

PMID- 19098635
TI  - TEE for managing a patient with mitral valve disease undergoing clipping of
      intracranial aneurysm.

PMID- 19098636
TI  - Open reduction and smooth Kirschner wire fixation for unstable slipped capital
      femoral epiphysis.
AB  - BACKGROUND: Reduction of unstable slipped capital epiphysis has a bad reputation,
      especially in severe slips. Treatment frequently causes avascular necrosis (AVN).
      This study analyzes the role of capsulotomy with evacuation of intraarticular
      fluid and gentle reduction done as an emergency procedure followed by fixation
      with unthreaded Kirschner wires (K-wires). METHODS: We treated 64 consecutive
      cases of unstable slips (37 boys and 27 girls) following the same protocol.
      Instability was recognized in those children who had experienced a fall or a
      stumble, followed by acute hip pain, with radiological evidence of capital
      femoral separation and ultrasonographic evidence of joint effusion. The protocol
      consisted of capsulotomy, evacuation of intraarticular effusion or hematoma,
      controlled gentle reduction, and fixation of the reduced physis by smooth K
      wires. Surgery was done as an emergency procedure if possible within 24 hours
      after the onset of acute symptoms. RESULTS: There were 20 mild slips with slip
      angles less than 31 degrees, 24 moderate with slip angles between 31 and 50
      degrees, 20 slips were severe with slip angles between 51 and 90 degrees. In 61
      cases, reduction was successful without being followed by AVN. Three patients, 2
      girls and 1 boy, developed partial AVN (4.7%). Two avascular necroses occurred in
      moderate slips, one in a severe slip, and none in the mild slips. The outcome of
      60 patients (34 boys and 26 girls) with unstable slips could be evaluated
      clinically and radiographically with a mean follow-up of 4.9 years (range, 18
      months-104 months). The Iowa hip score in these 60 cases reached an average of
      94.5 points out of 100. CONCLUSIONS: Open reduction and evacuation of
      intraarticular hemarthrosis or effusion detected by ultrasound and smooth K-wire
      fixation done as an emergency is a safe and reliable treatment option for
      unstable slips with a low AVN rate. The severity of the slip does not influence
      the rate of AVN and the outcome measured by the Iowa hip score.

PMID- 19098637
TI  - Intraarticular findings in symptomatic developmental dysplasia of the hip.
AB  - BACKGROUND: The purpose of this study was to examine intraarticular pathology in
      patients younger than 20 years with symptomatic developmental dysplasia of the
      hip. METHODS: We performed hip arthroscopy during corrective osteotomy in 23 hips
      in 22 patients. All patients were female, and the average age at operation was
      16.4 years. Eighteen hips were in a prearthritic stage, and 5 hips were in an
      early stage. The presence and location of cartilage degeneration and labral tears
      were evaluated. Second-look arthroscopy was performed in 13 hips in 12 patients.
      RESULTS: Fourteen hips (77.8%) in the prearthritic stage had cartilage
      degeneration. Cartilage lesions were more frequent in the acetabulum than in the
      femoral head (72.2% vs 16.7%). Sixty-one percent of acetabular lesions were
      located at the anterosuperior area. Labral tears were observed in 77.8% of hips
      in prearthritic stages located at the anterosuperior (72.2%) and superior (44.4%)
      areas. The degree of cartilage and labral lesions in the early stage was more
      severe than in the prearthritic stage. On second-look arthroscopy, there were no
      changes in the state of the cartilage and labrum in the majority (84.6%) of hips.
      CONCLUSIONS: The incidence of intraarticular lesions in developmental dysplasia
      of the hip was high, even in the prearthritic stage. These lesions tended to
      originate in the anterosuperior area of the acetabulum and were generally
      progressive.

PMID- 19098638
TI  - Post-closed reduction perfusion magnetic resonance imaging as a predictor of
      avascular necrosis in developmental hip dysplasia: a preliminary report.
AB  - INTRODUCTION: Avascular necrosis (AVN) of the femoral head remains a major
      complication in the treatment of developmental dysplasia of the hip (DDH) in
      infants. We performed a retrospective analysis to look at the predictive ability
      of postclosed reduction contrast-enhanced magnetic resonance imaging (MRI) for
      AVN after closed reduction in DDH. METHODS: Twenty-eight hips in 27 infants (aged
      1-11 months) with idiopathic hip dislocations who had failed brace treatment
      underwent closed reduction +/- adductor tenotomy and spica cast application under
      general anesthesia. Magnetic resonance imaging of the hips after intravenous
      gadolinium contrast injection for evaluation of epiphyseal perfusion was obtained
      immediately after cast application. Patients were followed with serial
      radiographs for a minimum of 1 year after closed reduction. Presence of AVN was
      determined by the presence of any one of the 5 Salter criteria by 2 readers.
      Magnetic resonance imaging was graded as normal, asymmetric enhancement, focal
      decreased enhancement, or global decreased enhancement by 2 radiologists.
      RESULTS: Six (21%) of 28 hips showed evidence of clinically significant AVN on
      follow-up radiographs. Fifty percent of the hips with AVN, but only 2 of 22 hips
      without AVN, showed a global decreased MRI enhancement (P < 0.05, Fisher exact
      test). Multivariate logistic regression indicated that a global decreased
      enhancement was associated with a significantly higher risk of developing AVN (P
      < 0.01), independently of age at reduction (P = 0.02) and abduction angle.
      CONCLUSIONS: In addition to accurate anatomical assessment of a closed reduction
      in DDH, gadolinium-enhanced MRI provides information about femoral head perfusion
      that may be predictive for future AVN. At present, it is premature to use the
      perfusion information for routine clinical use. However, it opens the door to
      studies looking at repositioning or alternative reduction methods that may reduce
      the risk of AVN in this higher risk group.

PMID- 19098639
TI  - Screw fixation to C2 in children: a case series and technical report.
AB  - BACKGROUND: Screw fixation into the axis (C2) provides a stable anchor for
      constructs encompassing the upper cervical spine or craniocervical spine. Screw
      fixation to C2 in the pediatric population is not well studied. METHODS: We
      reviewed the records of 17 pediatric patients who underwent surgical fixation to
      C2 for a variety of disorders. Operative reports, clinical charts, and computed
      tomography (CT) scans were reviewed to determine the presence of any
      intraoperative or postoperative screw-related complications. RESULTS: The mean
      age of our patients was 10 years (range, 3-16 years). Preoperative CT scans
      revealed unfavorable anatomy for pars/transarticular screw placement in 1 patient
      caused by a high-riding vertebral artery on 1 side and in 1 patient because of a
      sclerotic pars. Intraoperative findings revealed 1 patient who was unable to have
      transarticular screws, they subsequently underwent pars screw placement at C2 and
      lateral mass screws at C1. There was 1 screw-related complication: 1 patient had
      an excessively long screw noted on routine postoperative CT scanning and had the
      screw replaced with a smaller screw through the same tract. There were no
      vertebral artery injuries and no neurological injuries. At a mean follow-up of 20
      months (range, 13-36 months), all patients had obtained clinical union with no
      complications noted. CONCLUSIONS: In our series, screw fixation to C2 was
      possible in all patients. There were no major complications, and all patients
      have clinically united. The C2 screw fixation should be considered in all
      patients with appropriate preoperative imaging and adhering to surgical
      dissection of the pars.

PMID- 19098640
TI  - Previously unreported structure associated with Sprengel deformity.
AB  - Congenital elevation of the scapula (Sprengel deformity) is the most common
      congenital abnormality involving the scapula. In up to 50% of cases, there is an
      associated connection, which may be osseous, cartilaginous, or fibrous, between
      the scapula and the lower cervical spine. To date, there have been no reports of
      an osseous structure extending from the medial scapula to the clavicle and
      occipital region of the skull associated with Sprengel deformity.

PMID- 19098641
TI  - Simultaneous ipsilateral avulsion of the anterior superior and anterior inferior
      iliac spines in an adolescent.
AB  - BACKGROUND: Only one case of simultaneous avulsion fractures of the anterior
      superior and anterior inferior iliac spines has been previously reported. This
      was associated with a hip dislocation. METHODS: A 16-year-old male adolescent
      sustained ipsilateral avulsion fractures of his superior and inferior iliac
      spines from a hyperextension injury of his right hip in a skiing accident. He
      healed satisfactorily after nonoperative treatment with protected weight bearing
      and limited active hip range of motion. RESULTS: The patient healed in 12 weeks
      and returned to full activities, including sports, without complications.
      CONCLUSIONS: Conservative treatment of simultaneous ipsilateral avulsion
      fractures of the anterior superior and anterior inferior iliac spines can lead to
      a good outcome.

PMID- 19098642
TI  - Iatrogenic thoracic outlet syndrome secondary to vertical expandable prosthetic
      titanium rib expansion thoracoplasty: pathogenesis and strategies for
      prevention/treatment.
AB  - BACKGROUND: An innovative treatment for thoracic insufficiency syndrome involves
      a vertical expansion of the chest wall through a horizontal chest wall osteotomy
      maintained by a distraction device (vertical expandable prosthetic titanium rib
      or VEPTR). Upper-extremity neurovascular dysfunction has been reported after
      expansion. The purposes of this study are to identify potential etiologies for
      compression of the brachial plexus after expansion thoracoplasty and to suggest
      strategies to reduce the incidence of this complication. METHODS: A simulated
      VEPTR procedure was performed on 8 fresh cadaveric specimens. Manometric
      measurements were taken in the 3 anatomic regions of the thoracic outlet after
      thoracotomy and rib distraction were performed. Confirmation of the location of
      compression was performed by placing barium-impregnated putty along the course of
      the brachial plexus and evaluating the effect of expansion using video
      fluoroscopy. A midclavicular osteotomy was then performed and video fluoroscopy
      repeated. RESULTS: A 20% increase in pressure was seen in the costoclavicular
      region of the thoracic outlet after expansion. Constriction of the midclavicular
      region of the thoracic outlet between the first rib and clavicle was confirmed
      using the putty model. Midclavicular osteotomy alleviated this region of
      compression. CONCLUSIONS: Expansion thoracoplasty with the VEPTR procedure causes
      increased pressure in the costoclavicular region of the thoracic outlet. A
      midclavicular osteotomy may be one method to alleviate thoracic outlet narrowing
      after VEPTR procedure, although the short- and long-term effects of this is
      procedure is not known. CLINICAL RELEVANCE: Our model supports an iatrogenic
      thoracic outlet syndrome caused by expansion thoracoplasty. Based on our data as
      well as a review of the literature, we recommend intraoperative neurologic
      monitoring of the ipsilateral upper extremity during the VEPTR procedure.

PMID- 19098643
TI  - Early changes in pulmonary function after vertical expandable prosthetic titanium
      rib insertion in children with thoracic insufficiency syndrome.
AB  - BACKGROUND: The vertical expandable prosthetic titanium rib (VEPTR) has been
      inserted in children with thoracic insufficiency syndrome for the last decade to
      expand and support the chest and allow for further lung growth. There are minimal
      published data evaluating the postoperative change in lung function after VEPTR
      insertion. We hypothesize that there will be a significant increase in lung
      function after VEPTR insertion, and the earlier the insertion, the greater the
      improvement. METHODS: The Chest Wall Disorders Study Group Database, containing
      data before and after VEPTR insertion from 7 different centers, was queried for
      spirometry and lung volume measurements, and the data were analyzed to assess the
      short-term effect on lung function of VEPTR placement. RESULTS: There was a
      statistically significant decrease in forced vital capacity, forced expiratory
      volume in 1 second as a percent of predicted, an increase in residual volume (RV)
      that did not reach statistical significance, and there was no change in total
      lung capacity at the first postoperative visit (7.7 +/- 4.8 months). There was a
      significant decrease in Cobb angle. There was no correlation between absolute
      change in any pulmonary function and Cobb angle age at the time of surgery.
      CONCLUSIONS: Although there is a clinically and radiographically apparent
      expansion of the thorax after VEPTR insertion, there is no similar improvement in
      lung volume, and instead there is a decrease in forced vital capacity and
      increase in residual volume, the explanation for which requires further study.
      This lack of change in pulmonary function after VEPTR insertion suggests that the
      benefit of VEPTR insertion may lie more in stabilizing the thorax and improving
      respiratory mechanics measured in other ways.

PMID- 19098644
TI  - Immediate incorporated hip spica casting in pediatric femoral fractures:
      comparison of efficacy between normal and high-risk groups.
AB  - BACKGROUND: Immediate hip spica casting is the most commonly used method for the
      treatment of pediatric femoral fractures. The main disadvantage of the method is
      the unacceptable shortening (>25 mm), which may occur during the treatment.
      Buehler et al described the so-called telescope test to identify the cases with a
      relatively high risk of unacceptable shortening. On the basis of this test,
      patients with an overriding of the fracture ends of more than 30 mm have a 20.4
      times higher risk of unacceptable shortening compared with those with an
      overriding of less than 30 mm. This relatively higher risk of unacceptable
      shortening may be avoided by a hip spica cast, which is incorporated to a distal
      femoral traction pin. METHODS: The study consists of 47 (26 boys and 21 girls)
      patients. Mean age was 40.3 months (range, 18 months to 6 years). Patients were
      divided into 2 groups according to the telescope test. Group 1 included patients
      with telescope test results of more than 30 mm. Group 2 included patients with
      telescope test results of 30 mm or less. All patients were treated with a hip
      spica cast, which is incorporated to a distal femoral traction pin within 8 hours
      of the initial trauma. During cast treatment, patients were followed up by weekly
      x-ray controls for the first month. Patients were assessed for unacceptable
      shortening and misalignment. RESULTS: Mean (SD) shortening during cast treatment
      was 2.9 (5.1) mm on the treated site. Shortening was detected in 16 patients
      (88.9%) in group 1 and in 7 patients (24.1%) in group 2. A significantly higher
      number (P < 0.001) of patients developed shortening in group 1. However,
      unacceptable shortening (>25 mm) did not develop in any patient in both groups.
      There was no significant frontal plane malalignment in both groups (P > 0.05).
      Sagittal plane malalignment was significantly higher in group 1 (P < 0.05).
      CONCLUSIONS: Hip spica cast, which is incorporated to a distal femoral traction
      pin, avoids unacceptable shortening and frontal plane malalignment in pediatric
      femoral fractures, which even have a relatively high risk of unacceptable
      shortening based on the so-called telescope test. However, the technique cannot
      avoid sagittal malalignment.

PMID- 19098645
TI  - Biomechanical study of flexible intramedullary nails.
AB  - BACKGROUND: Flexible intramedullary (IM) nailing is considered a safe, minimally
      invasive fixation technique with relatively low complication rates for long-bone
      fractures in the pediatric population. At our institution, questions have arisen
      about stability of fixation based on the distance of the nail past the fracture
      site. Clinically, this question arises with proximal or distal fractures and when
      the nail is unable to be passed to the desired distance past the fracture site.
      The purpose of our study was to compare biomechanical resistance with bending
      forces for fixation constructs whose IM nails are at differing distances beyond
      the fracture site in different bones. METHODS: This study tested matched pairs of
      canine radii, ulnas, and tibias in 4-point bending and compared the biomechanical
      properties of length of nail fixation past the fracture site in relation to bone
      diameter. RESULTS: Fixations of 1 or 2 diameters past the osteotomy yielded gross
      instability. There was no difference found in bending failure force,
      displacement, stiffness, or energy when comparing 3 versus 5 diameters of
      fixation past the fracture site. CONCLUSIONS: Flexible IM nails act as internal
      splints to align the fracture ends. At 3 diameters or more beyond the fracture
      site, the length does not significantly affect the biomechanical properties of
      the construct. CLINICAL RELEVANCE: Flexible IM nails act as internal splints to
      align the fracture ends. At 3 diameters or more past the fracture site, the
      length of the nail does not greatly affect the biomechanical properties of the
      construct. This knowledge may be helpful in clinical scenarios where there is
      uncertainty about the expected strength of a shorter fixation. Examples include
      when the nail cannot be passed completely to the distal metaphysis and in
      proximal or distal long-bone fractures. Further clinical studies are needed to
      determine implications in a patient setting.

PMID- 19098646
TI  - Nonoperative management of pediatric grade 1 open fractures with less than a 24
      hour admission.
AB  - BACKGROUND: The purpose of this study was to evaluate the results of nonoperative
      management of pediatric grade 1 open fractures treated either in the emergency
      room only or with a less than 24-hour admission. METHODS: A retrospective chart
      review was done on all patients with this type of injury who were treated by
      nonoperative modalities in the emergency room and who were admitted for no more
      than 24 hours for administration of intravenously administered antibiotics. Our
      population included 25 patients who were followed up until healing was confirmed
      clinically and radiographically. RESULTS: One patient with persistent
      serosanguineous drainage from the wound site and fever was admitted for 48 hours
      of intravenously administered antibiotics for presumed infection. That patient
      went on to heal both clinically and radiographically without further
      complication. Therefore, our infection rate was 4.0%. CONCLUSIONS: This study
      demonstrates the safe nonoperative treatment of grade 1 open fractures in our
      pediatric population. This management eliminates any possible anesthetic risk as
      well as significantly decreases the cost of caring for these patients in the
      health care system.

PMID- 19098647
TI  - Hemiepiphyseal stapling for angular deformity correction around the knee joint in
      children with multiple epiphyseal dysplasia.
AB  - BACKGROUND: Angular deformity around the knee joint in patients with multiple
      epiphyseal dysplasia (MED) causes alteration in knee biomechanics as well as
      cosmetic problem. We report angular correction by hemiepiphyseal stapling (HES)
      and physeal behavior after stapling removal in MED patients. METHODS: In 17 knees
      of 9 MED patients, 16 distal femoral and 8 proximal tibial physes were stapled.
      Age at operation ranged from 8.2 to 13.9 years. Thirteen knees were in valgus
      alignment and 3 in varus and were followed up for an average of 3.9 years.
      Angular deformity change was evaluated by the anatomical lateral distal femoral
      angle or anatomical medial proximal tibial angle. Mechanical axis deviation was
      defined as the percentage ratio of distance from the knee joint center to
      mechanical axis divided by half the width of the tibial plateau. RESULTS: Amount
      of angular correction by HES at the distal femur was 15.3 +/- 6.4 degrees for an
      average of 17.4 months, and at the proximal tibia, 8.6 +/- 2.0 degrees for an
      average of 13.4 months. Twelve distal femoral physes remained stationary (angular
      change <3 degrees) and 4 rebounded (loss of correction >3 degrees) after staple
      removal, whereas 5 proximal tibial physes remained stationary, 2 rebounded, and 1
      was progressive. Neither hardware problems nor clinical complications other than
      overcorrection or undercorrection were encountered. At the latest follow-up,
      mechanical axis deviation remained within +/-50% in 14 of 17 knees. The remaining
      3 knees failed because of premature closure of the distal femoral physis, causing
      undercorrection of the deformity, insufficient rebound of an overcorrected knee,
      or progressive angular change after staple removal. CONCLUSIONS: Hemiepiphyseal
      stapling is effective for angular correction in MED with minimal surgical insult.
      However, as physeal behavior after staple removal is rather unpredictable,
      overcorrection over zone 1 should be avoided, and close monitoring is mandatory
      until skeletal maturity.

PMID- 19098648
TI  - Failure of Orthofix eight-Plate for the treatment of Blount disease.
AB  - BACKGROUND: Hemiepiphysiodesis is a well-established treatment option for angular
      deformities of the knee. Recently, our institution began using the eight-Plate
      tension band device by Orthofix (McKinney, Tex) as an alternative to staples.
      However, several patients have returned with broken screws necessitating revision
      surgery. METHODS: Charts and radiographs of all patients who were treated with
      the eight-Plate (Orthofix) at our institution were reviewed. The diagnosis, age,
      amount of angular deformity, weight, and body mass index were analyzed with
      respect to eventual implant failure. RESULTS: Implant failure occurred in 8 (26%)
      of 31 proximal tibia constructs. All 8 failures occurred in patients with Blount
      disease and involved breakage of the tibial metaphyseal screw. The mean time to
      failure was 13.6 months. Eight hardware failures in 18 Blount disease extremities
      represent a failure rate of 44%. No implant failures occurred in the remaining
      diagnoses. Neither age nor degree of deformity correlated with implant failure.
      The failure group was significantly heavier than the nonfailure group, and the
      patients with Blount disease were found to be heavier than the other patients.
      However, no significant difference in weight was found within the Blount group
      regarding implant failure. In all patients whose plates did not fail, rate of
      correction was equal to or better than previously reported hemiepiphysiodesis
      studies. CONCLUSIONS: The eight-Plate (Orthofix) is a reasonable option for
      hemiepiphysiodesis but has an unacceptable failure rate in Blount disease (44%).
      There were no instances of failure in patients with other diagnoses. In Blount
      disease, stronger implants should be considered. Future implant designs should
      include stronger screws to decrease implant failure complications.

PMID- 19098649
TI  - The effect of periosteal resection on tibial growth velocity measured by
      microtransducer technology in lambs.
AB  - BACKGROUND: Disruption of the periosteum, whether traumatic or elective, has long
      been known to accelerate growth in the developing skeleton. However, the extent,
      timing, and mechanism of the resultant increase in growth velocity (if any)
      remain undefined. The primary research questions were: Does periosteal resection
      result in a change (increase) in growth velocity of a long bone at the growth
      plate? When does the effect start after the resection and for how long? Finally,
      which of several cellular mechanisms is most likely responsible for the change in
      growth velocity? METHODS: Five lambs underwent proximal tibial growth plate
      periosteal resection with subsequent measurement of growth velocity by
      implantable microtransducers or fluorochrome labeling. This former technique
      provided real-time growth velocity data with a resolution of about 10 microm
      (width of a proliferative zone chondrocyte). These measurements were accurate at
      up to 4 weeks postoperative, as verified by fluorochrome labeling, and
      radiographic measurement. Two lambs were continued on the study for an additional
      3 weeks. Histomorphometric and stereological assessments of chondrocytic kinetic
      parameters were performed on control and experimental tibiae after euthanasia.
      RESULTS: Periosteal resection increased growth velocity in every lamb, at every
      time point, and in a consistent and sustained manner. Histomorphometric
      correlation to this phenomenon indicated that the cellular basis of this
      acceleration was most likely the result of hypertrophic chondrocyte axial
      elongation rather than changes in chondrocyte proliferation, magnitude of
      hypertrophic chondrocytic swelling, or increased matrix production. CONCLUSIONS:
      Periosteal resection creates immediate and sustained acceleration of growth
      resulting from axial elongation of the hypertrophic chondrocyte. Although the
      increase in growth velocity was consistent, the absolute magnitude of the
      acceleration suggests that periosteal resection be considered as an adjunct to
      other primary procedures. Periosteal resection may serve as a useful clinical
      adjunct to provide a modest growth stimulus in cases of hemihypertrophy or
      angular limb deformity or to counteract the growth inhibition seen when
      performing distraction osteogenesis.

PMID- 19098650
TI  - The effects of femoral derotation osteotomy in children with cerebral palsy: an
      evaluation using energy cost and functional mobility.
AB  - BACKGROUND: The effect of femoral derotation osteotomy (FDO) in children with
      cerebral palsy (CP) has hitherto been examined using various outcome measures
      including range of motion of lower extremity joints and gait parameters. However,
      functional ambulation following this procedure has been scarcely investigated.
      OBJECTIVE: To evaluate the effect of FDO on energy cost during stair climbing and
      functional mobility in children with CP. METHOD: A prospective case series study
      was conducted on 18 children with CP, 11 at Gross Motor Functional Classification
      System (GMFCS) II and 7 with GMFCS III, aged 8.5 +/- 1.24 years (range, 6.9-11
      years) who underwent FDO to correct hip internal rotation. The energy cost was
      measured using the heart beat cost index (HBCI) during stair climbing test,
      whereas functional mobility was assessed using the Gillette Functional Assessment
      Questionnaire (FAQ). Tests were administered before surgery (P0), 6 months (P1),
      and at approximately a year postoperatively (P2). RESULTS: Compared with P0,
      significant changes in hip rotation were observed at P1 and P2. There was a
      significant improvement in HBCI from P0 to P2, whereas FAQ improved significantly
      from P1 to P2. A moderate correlation was found between HBCI and GMFCS at all
      times (r = 0.61-0.78). Negative correlations were found between the HBCI and FAQ
      and between GMFCS and FAQ at all times (r = -0.5). CONCLUSION: This study
      indicates that children with CP may benefit functionally from FDO as judged by
      HBCI and functional mobility rating.

PMID- 19098651
TI  - Correlation between lower limb bone morphology and gait characteristics in
      children with spastic diplegic cerebral palsy.
AB  - BACKGROUND: Children with spastic diplegic cerebral palsy (CP) exhibit abnormal
      walking patterns and frequently develop lower limb, long bone deformities. It is
      important to determine if any relationship exists between bone morphology and
      movement of the lower limbs in children with CP. This is necessary to explain and
      possibly prevent the development of these deformities. METHODS: This study
      investigated the relationship between bone morphology and gait characteristics in
      10 healthy children (age range, 6-13 years; mean, 8 years 7 months; SD, +/-2
      years 7 months) and 9 children with spastic diplegic CP (age range, 6-12 years;
      mean, 9 years 2.5 months; SD, +/-1 year 10.5 months) with no previous surgery.
      Three-dimensional magnetic resonance images were analyzed to define bone
      morphology. Morphological characteristics, such as the bicondylar angle, neck
      shaft angle, anteversion angle, and tibial torsion, were measured. Gait analyses
      were performed to obtain kinematic characteristics of CP and normal children's
      gait. Principal component analysis was used to reduce the dimensionality of 27
      parameters (26 kinematics variables and age of the children) to 8 independent
      variables. Correlations between gait and bone morphology were determined for both
      groups of children. RESULTS: Results indicated that in healthy children, hip
      adduction was correlated with neck-shaft and bicondylar angles. In CP children,
      pelvic obliquity correlated with neck-shaft angle, and foot rotation with
      bicondylar angle. In the transverse plane, hip and pelvic rotational kinematics
      were related to femoral anteversion in healthy children and to tibial torsion in
      CP children. CONCLUSION: Different development was observed in femoral and tibial
      morphology between CP and healthy children. The relationship between bone shape
      and dynamic gait patterns also varied between these populations. This needs to be
      taken into account, particularly when surgical treatment is planned. CLINICAL
      RELEVANCE: Understanding the relationship between gait abnormality and bone
      deformity could eventually help in developing treatment regimens that will
      address gait deviations at the correct level and promote normal bone growth in
      children with CP.

PMID- 19098652
TI  - Postoperative orthopaedic neurovascular monitoring in the pediatric population.
AB  - BACKGROUND: Many orthopaedic procedures carry risks of neurovascular compromise.
      We hypothesized that risk factors for neurovascular compromise and for its
      delayed detection exist in the pediatric orthopaedic population. METHODS: We
      searched our institution's pediatric patient database from January 2004 through
      December 2006, randomly selecting (arbitrarily choosing every 20th patient) 286
      patients, 34 of whom went to the operating room twice for 320 procedures. We
      retrospectively reviewed their records for these potential risk factors: altered
      communication ability (for age), abnormal baseline neurovascular status,
      imprecise documentation of neurovascular baseline status, nonspecific or
      inappropriate postoperative monitoring orders, and monitoring not carried out by
      nursing staff. Outcomes were analyzed via Fisher exact test (P < 0.05). RESULTS:
      Ten patients (3%) had new postoperative neurovascular events, and 4 (1%) were
      recognized to have neurological deterioration detected on a delayed basis. Fifty
      seven (18%) had impaired communication ability (significant correlation with
      increased risk for neurovascular events), 97 (30%) had abnormal neurovascular
      preoperative status, and 21 (22%) had no specific documentation of neurovascular
      condition in the perioperative chart. Insufficient documentation of abnormal
      neurovascular baseline correlated significantly with an increased risk for
      delayed detection of postoperative neurovascular events. Although all written
      orders for neurovascular checks were carried out and specific with respect to
      timing, 133 patients (42%) had neurovascular monitoring orders that were
      nonspecific about the functions to be checked. All patients with delayed deficit
      detection had impaired ability to communicate, abnormal baseline values, or
      improperly written orders. CONCLUSIONS: The risk of postoperative neurovascular
      events is significantly higher in patients with impaired communication ability,
      and the risk for delayed detection of such events is significantly higher in
      patients without proper documentation of an abnormal neurovascular baseline.
      Clear documentation of baseline function may avoid delayed detection, and more
      specific monitoring processes may improve patient safety.

PMID- 19098653
TI  - Comparative severity of pediatric osteomyelitis attributable to methicillin
      resistant versus methicillin-sensitive Staphylococcus aureus.
AB  - BACKGROUND: Staphylococcus aureus remains the most common etiology of
      hematogenous osteomyelitis in children. Recently emerged virulent strains of
      methicillin-resistant S. aureus (MRSA) strains now predominate. It remains
      uncertain whether these pathogens cause a measurably more severe illness than
      methicillin-sensitive strains. METHODS: We reviewed records of 97 pediatric
      patients with hematogenous osteomyelitis of varying etiologies to determine
      whether there were significant differences among the groups in terms of
      predetermined measures of disease severity. These measures included degree and
      duration of elevated temperature, acute-phase reactants, length of
      hospitalization, the number of surgical procedures required, and long-term
      sequelae. RESULTS: Differences in the clinical course of illness were observed.
      Patients with MRSA had a significant increase in degree and duration of elevated
      temperature (P = 0.0001 for both), acute-phase reactant measures (white blood
      cell count, P = 0.0001; C-reactive protein, P = 0.0058; erythrocyte sedimentation
      rate, P = 0.0046), initial length of hospital stay (P = 0.0001), and surgical
      interventions (all procedures, P = 0.0001; therapeutic procedures, only P =
      0.0002) as compared with patients with osteomyelitis caused by other bacterial
      pathogens and culture-negative osteomyelitis. A similar general pattern was
      observed when the analysis was restricted to culture-positive staphylococcal
      cases only. CONCLUSIONS: Our results support the hypothesis that MRSA produces
      more severe bone infection and is likely to require more aggressive surgical and
      medical management.

PMID- 19098654
TI  - Peripheral arthropathy in hereditary sensory and autonomic neuropathy types III
      and IV.
AB  - BACKGROUND: To determine the features of the underlying destructive arthropathy
      in the peripheral joints of children with hereditary sensory and autonomic
      neuropathy (HSAN) type III and to compare and contrast this to the arthropathy
      noted in HSAN type IV, as both groups experience decreased pain perception.
      METHODS: From a database of 547 patients with HSAN type III and 32 patients with
      HSAN type IV, we performed a retrospective chart review and radiographic analysis
      of all patients who presented with joint swelling and deformity. Underlying joint
      pathology was classified as either osteonecrosis or Charcot arthropathy. RESULTS:
      In the HSAN type III population, 44 (8%; 22 males and 22 females) of the 547
      patients had clinical evidence of arthropathy. In 42 patients, 48 joints
      demonstrated radiographic evidence of osteonecrosis; 45 (94%) of the 48 joints
      with osteonecrosis occurred in the lower extremity. In each case of osteonecrosis
      of the knee (n = 19), isolated involvement of the lateral distal femoral condyle
      was seen consisting of varying sizes of posterolateral osteochondral
      fragmentation. In the 32 patients comprising the HSAN type IV population, 18
      (56%) were found to have radiographic findings consistent with Charcot
      arthropathy in a total of 30 affected joints. One patient demonstrated Charcot
      arthropathy of the spine and subsequent progressive spondylolisthesis. Nine
      patients (12 joints) also demonstrated osteomyelitis. CONCLUSIONS: In patients
      with HSAN type III, osteonecrosis is the initial lesion preceding destructive
      arthropathy. Osteonecrosis and osteochondral fragmentation were always isolated
      at the lateral distal femoral condyle in the knee. This pathology may be amenable
      to surgical reconstruction and fixation to stabilize the knee and prevent further
      degeneration. Hereditary sensory and autonomic neuropathy type IV was most
      commonly associated with Charcot arthropathy or joint subluxation and
      dislocation. Late secondary changes at the articular surface may make
      radiographic distinction difficult. Charcot arthropathy affected both sides of
      the involved joint with evidence of collapse and fragmentation. With
      osteonecrosis, the articular process was found to be more focal.

PMID- 19098656
TI  - Effect of heated and humidified carbon dioxide on patients after laparoscopic
      procedures: a meta-analysis.
AB  - OBJECTIVE: To systematically analyze the role of heated humidified carbon dioxide
      (CO2) in laparoscopy. METHODS: Clinical trials on laparoscopic procedures using
      standard dry CO2 versus heated humidified CO2 for pneumoperitoneum were analyzed.
      RESULTS: Ten randomized controlled trials on 565 patients were analyzed. In both
      the fixed and random effect models, postoperative pain was significantly less in
      heated humidified CO2 group. Heated humidified CO2 group was also associated with
      significantly lower risk of hypothermia and lower analgesic requirement. However,
      statistically there was no difference in total hospital stay and lens fogging
      rate. CONCLUSIONS: The use of heated humidified CO2 for pneumoperitoneum in
      laparoscopic procedures is associated with lesser postoperative pain, lower risk
      of postoperative hypothermia, and lower analgesic requirements. However, total
      hospital stay and lens fogging rates do not differ. Hence, the heated and
      humidified CO2 may be considered as the first choice for pneumoperitoneum in
      laparoscopic procedures.

PMID- 19098655
TI  - Fetal surgery of extremity amniotic bands: an experimental model of in utero limb
      salvage in fetal lamb.
AB  - BACKGROUND: Extremity amniotic band (EAB) syndrome can cause an intrauterine
      amputation as a result of a mechanical effect with progressive strangulation. The
      aim of the study is to assess the use of fetal surgery of EABs with risk of
      amputation in the ovine fetus. METHODS: Right limbs of fifteen 60-day-gestational
      age fetal sheep were ligated with silk suture at the infracondylar level. Left
      limbs were used for paired comparison. Fetuses were randomized into 3 groups: an
      early-repair group (n = 5), a late-repair group (n = 5), and a nonrepaired group
      (n = 5). The limbs of the 2 repaired groups underwent fetal release. The limbs
      obtained from at-term fetuses were analyzed morphologically, functionally, and
      radiologically. Statistical analysis with paired test was used to compare data.
      RESULTS: Nonrepaired limbs showed amputation or quasi amputation; the repaired
      ones did not. However, those late-repaired had significantly reduced passive
      ankle range of motion, shorter limb length, and mild residual changes.
      CONCLUSIONS: Intrauterine release of potentially severe EABs prevents limb
      amputation and leads to morphofunctional recovery. Early release shows better
      results. CLINICAL RELEVANCE: : Intrauterine amputations caused by EABs in the
      human fetus might be avoidable by fetal surgery.

PMID- 19098657
TI  - Routine administration of antibiotics to patients suffering accidental
      gallbladder perforation during laparoscopic cholecystectomy is not necessary.
AB  - INTRODUCTION: Accidental rupture of the gallbladder is an event which occurs in
      up to 20% of laparoscopic cholecystectomies, mainly in those where dissection is
      difficult, or during extraction when the gallbladder is withdrawn directly
      through the laparoscope port. It has been commonly assumed that contamination by
      bile in the abdominal cavity could be a cause of infection and lead to the
      formation of a residual abscess or even to surgical wound infection. It is common
      practice, therefore, for the surgeon to prescribe the application of an
      antibiotic at the moment when gallbladder perforation occurs. OBJECTIVE: To
      compare 2 groups of similar patients, to determine whether administration of
      antibiotics, started during surgery, is actually useful in reducing the risk of
      residual abscess or infection in the surgical wound. PATIENTS AND METHOD: The
      study considered a total of 166 patients who had suffered accidental perforation
      of the gallbladder during elective laparoscopic cholecystectomy. This total was
      divided at random into 2 groups: group A (80 patients) who received a dose of 1 g
      of Cefotaxime at the moment of gallbladder rupture, followed by 2 more doses at
      intervals of 8 hours in the immediate postoperative period; and group B (86
      patients) who did not receive any antibiotic treatment at all. The dependent
      variables observed were surgical wound infection and residual abscess: and the
      control variables were age, sex, length of operation time, intercurrent
      illnesses, and American Society of Anesthesiologists (ASA) classification.
      RESULTS: Two patients (2.5%) in group A developed a surgical wound infection,
      against 3 cases (3.4%) in group B, the result having no statistical significance.
      No patients developed residual abscess. In a multivariant analysis, the following
      were identified as independent factors significantly associated with the onset of
      surgical wound infection (P<0.001): diabetes mellitus, being over 60 years of
      age, operation time lasting longer than 70 minutes, and ASA 3. CONCLUSIONS:
      Routine application of an antibiotic to patients experiencing accidental
      perforation of the gallbladder during laparoscopic cholecystectomy is not
      necessary. In the case of patients with diabetes mellitus, those who are older
      than 60, or who have an ASA classification of 3 or more, or if the operation
      itself is likely to last more than 70 minutes, the recommendation is to start
      antibiotic therapy in the preoperative phase immediately before surgery.

PMID- 19098658
TI  - Early experience with laparoscopic major liver resections: a case-comparison
      study.
AB  - Laparoscopic major liver resections are regarded as demanding operations whose
      convenience is still under evaluation. The aim of the present study was to report
      our early experience and to describe surgical technique of laparoscopic major
      liver resections. Study group consisted of 6 female patients with benign disease
      and a mean age of 40.5 years, who underwent right hepatectomy in 4 cases and left
      hepatectomy in 2 cases. No mortality was observed. Morbidity consists in 1
      biliary fistula that requires rehospitalization and a new laparoscopic operation.
      The mean operative time was of 201.7 minutes, with a mean hospital stay of 5.5
      days. The authors conclude that laparoscopic major liver resections could be
      performed, at least for benign disease and by surgeons experienced in
      laparoscopy, with good results. Nevertheless, further studies are required before
      to draw definitive conclusions, especially for neoplastic patients who represent
      the most relevant group.

PMID- 19098659
TI  - Laparoscopic approach for small bowel tumors.
AB  - AIM: To review the outcome of laparoscopic small bowel resections as compared
      with open resection for small bowel tumors. METHOD: Retrospective review
      comparing total laparoscopic to open resections for small bowel tumors from
      October 1998 to July 2005 in a single centre. RESULTS: During the study period, 9
      patients underwent laparoscopic resection, whereas 11 patients underwent open
      small bowel resection. Majority of the patients (75%) suffered from
      gastrointestinal stromal tumors. Median operative time in both groups was
      comparable, but the median operative blood loss was significantly less in the
      laparoscopic group. (5 vs. 165 mL, P=0.005). The amount of oral dologesic used
      postoperatively was similar, whereas the use of intravenous morphine was
      significantly less in the laparoscopic group (7.4 vs. 21.3 mg, P=0.007). The
      median postoperative hospital stay was significantly shorter in the laparoscopic
      group (7 vs. 12 d, P=0.018). For patients with gastrointestinal stromal tumors, 2
      patients (29%) in the laparoscopic group and 3 patients (38%) in the open group
      had recurrence of disease during follow-up (P=0.573). CONCLUSIONS: Laparoscopic
      resection resulted in favorable short-term outcome compared with open resection
      for small bowel tumors in selected cases. The oncologic outcome is not
      compromised with this approach.

PMID- 19098660
TI  - The role of laparoscopy in the treatment of complications after colonoscopy.
AB  - Perforations of the colonic wall or splenic injury during colonoscopy are rare
      complications. Treatment of these complications by laparoscopy is an advisable
      compromise instead of an invasive surgery with a laparotomy or a noninvasive and
      potentially risky nonoperative therapy. All surgical procedures that can be
      performed by open approach can also be performed laparoscopically. We present in
      this report 15 patients who were treated for a perforation after colonoscopy. In
      addition, 2 cases of splenic injury after colonoscopy are described. Twelve
      perforations were sutured laparoscopically and 3 perforations were sutured via
      laparotomy. Except for 1 minor wound infection, there were no complications. One
      splenic injury was treated by spleen wrapping via an open approach due to former
      pancreatic surgery, and 1 injury was treated laparoscopically with a
      hemostypticum. Mortality was 0%. Early laparoscopic intervention is a safe and
      effective method in the treatment of serious complications after colonoscopy.

PMID- 19098661
TI  - Efficacy and safety of endoscopic balloon dilation of benign anastomotic
      strictures after oncologic anterior rectal resection: report on 24 cases.
AB  - Colorectal anastomotic benign strictures represent a challenging complication.
      Endoscopic dilation represents a valid and safe treatment. The purpose of this
      study is to retrospectively investigate the results of endoscopic balloon
      dilation for anastomotic stricture after anterior rectal resection for cancer in
      an institution. Twenty-four symptomatic patients with benign colorectal
      anastomotic stricture were treated between April 2001 and January 2005. All
      patients underwent dilation using through-the-scope balloon technique. The
      success of dilation, the number of sessions required, complications, recurrence,
      and the relationship between the number of dilation sessions and recurrence were
      assessed. Dilation was successful in 22 (91.7%) patients. There were no procedure
      related complications. The mean number of sessions required was 2.3. There was no
      relationship between the number of dilation sessions and stricture recurrence.
      Through-the-scope dilation is effective and safe for benign colorectal
      anastomotic strictures after anterior resection. There was no relationship
      between the number of dilation sessions and recurrence.

PMID- 19098662
TI  - Fibrin glue fixation of bioactive extracellular matrix mesh compared with soft
      prolene mesh for laparoscopic hernia repair.
AB  - INTRODUCTION: A comparison between soft prolene mesh and bioactive extracellular
      matrix prosthetic mesh fixed and secured with fibrin glue was studied. METHODS: A
      retrospective study of 160 patients operated upon by a single surgeon at the same
      institution over the past year was reviewed. There were 36 patients who had
      fibrin glue used as the sole means to fix the mesh in place during laparoscopic
      hernia repair. The patients were further subdivided into the type of mesh used,
      age, operative time, and postoperative events, and the results were analyzed.
      RESULTS: Bioactive extracellular matrix mesh was used in 18 patients and 23
      repairs. There were 21 indirect hernias and 2 direct hernias repaired. Age
      averaged 36 years (17 to 63) and operative time averaged 30 minutes (19 to 45).
      Three patients experienced mild bladder "burning" and 3 patients had mild groin
      pain postoperatively. No recurrences have occurred. "Soft" prolene mesh was used
      in 18 patients and 23 repairs. There were 14 indirect hernias and 9 direct
      hernias repaired. Age averaged 50 years (35 to 72) and operative time averaged 26
      minutes (20 to 40). Three patients had prolonged groin tenderness with or without
      ecchymosis lasting 3 weeks and 2 patients needed a foley catheter for 1 week for
      urinary retention. No recurrences have occurred. CONCLUSIONS: Fibrin glue has
      been used as a fixation technique for laparoscopic hernia repair with mesh. The
      bioactive extracellular matrix mesh patients had a slight increased groin/bladder
      discomfort that subsided in time. Neither group had a hernia recurrence noted
      over the study time. The use of biologic materials in the repair of hernia is an
      intriguing concept. It will be needed for studying long-term efficacy.

PMID- 19098663
TI  - The hemodynamic effects of CO2-induced pressure on the kidney in an isolated
      perfused rat kidney model.
AB  - BACKGROUND: Variable mechanisms were suggested to mediate the changes in renal
      hemodynamics during pneumoperitoneum. To assess whether it can be pressure
      dependent only, we conduct a study in an isolated, pressurized, and perfused
      organ model. METHODS: Seventy Wistar rat kidneys were perfused with oxygenated,
      3% albumin-contained Krebs-Henseleit solution. Experiments took place within
      Plexiglass chamber that provided conditions for perfusion of organs, humidity,
      and maintenance of intracameral CO2 pressures [0 (control), 3, 5, 8, 12, 15, and
      18 mm Hg]. All kidneys (10/group) were perfused for 60 minutes. One-half of the
      groups were perfused for an additional 30 minutes, during which the perfusion
      pressures were reduced to 0 mm Hg. pH of the perfusate was measured as well.
      RESULTS: The perfusion pressure increased and the kidney flow decreased slightly,
      in proportion with the intrachamber pressure. Urine output decreased to a minimum
      of 40% in >or=8 mm Hg pressure conditions, compared with the control group. The
      pH values were below normal, during experimental pneumoperitoneum. CONCLUSIONS:
      Pneumoperitoneal conditions are a direct cause of changes in renal urinary
      output. The increase in pCO2 pressure and consequently low intraorgan pH may
      contribute to a mild transient renal damage during pneumoperitoneum.

PMID- 19098664
TI  - Urologic laparoscopy in a Danish county hospital: indications and results.
AB  - OBJECTIVE: To describe laparoscopic surgeries performed over a 5-year period in a
      low-volume hospital, by type of operation and complications. MATERIALS AND
      METHODS: A total of 235 patients underwent laparoscopic procedures. All cases
      were prospectively recorded in a database and then reviewed. RESULTS: The most
      frequent operations were nephrectomy in 66 patients, pelvic lymph node dissection
      in 38 patients, varicocelectomy in 38 patients, pyeloplasty in 28 patients, and
      placement or replacement of peritoneal dialysis catheters in 21 patients. The
      complication rate was 6.4% (15 cases), with 1.3% visceral (3 patients) and 5.1%
      port site-related (12 patients). The mortality rate was 0.4% (1 patient). The
      conversion rate was 4.7% due to vascular injuries during dissection near the
      kidney hilus (6 patients) or slow progression/adhesions (5 patients). The
      reoperation rate was 1.6% (4 patients). Six patients received blood transfusions.
      CONCLUSIONS: Urologic laparoscopy is a safe modality in a low-volume country
      hospital, with no evidence of increased morbidity and mortality.

PMID- 19098665
TI  - Lessons learned from long-term university training in minimally invasive surgery
      in Spain.
AB  - PURPOSE: Starting from our prolonged experience in university minimally invasive
      surgery training (1993 to 2005), we aim to analyze the most important differences
      in participants' requirements from these courses along this time span. METHODS:
      Surveys' answers from the 6 first course editions (from 1993 to 1999, group 1)
      are compared with the last 6 ones (from 1999 to 2005, group 2), for a number of
      items including reasons to choose these courses, opinion about duration of
      training minimally invasive surgery (MIS) courses, responsibility of training
      MIS, and opinion about experimental training with animals. RESULTS: Total number
      (N) of participants was 341, with 177 in group 1 and 164 in group 2. The most
      important feature was the number of hours of animal training (61% from group 1
      vs. 75% from group 2, P<0.05). There was a trend to consider hospitals as more
      responsible (68.3% from group 1 vs. 83.5% from group 2, P=0.06) and the
      University as less responsible for MIS training (36.7% from group 1 and 18.2%
      from group 2, P=0.01). Laparoscopic training courses should last at least 1 year
      (76.7% from group 1 vs. 78.2% from group 2, not significant). CONCLUSIONS: The
      time dedicated to practical training is highly appreciated by participants in
      training courses. Furthermore, we have not found many changes in trainees'
      requirements from MIS training courses over the last 12 years.

PMID- 19098666
TI  - A simple technique for large tumor removal during laparoscopic liver resection.
AB  - Experience with laparoscopic liver resections has increased in recent years, and
      so have the number of patients operated on by minimally invasive techniques.
      Specimen extraction is an important step of laparoscopic liver resection. The
      size of the specimen is usually a limitation for the use of laparoscopy. The aim
      of this paper is to describe a new technique combining Pfannenstiel suprapubic
      incision and obstetric forceps to remove a large specimen from laparoscopic liver
      resections. The present technique allows an expeditious extraction of intact
      specimens, even huge ones, through a standard suprapubic Pfannenstiel incision.
      This technique has additional functional and cosmetic advantages over other
      techniques of specimen retrieval. We believe that the described technique is
      feasible, can be easily and rapidly performed, and facilitates laparoscopic liver
      resection by reducing the technical difficulties for specimen removal and may
      also be used in other abdominal laparoscopic interventions that deal with large
      surgical specimens.

PMID- 19098667
TI  - Technical feasibility of endoscopic submucosal dissection of gastrointestinal
      epithelial neoplasms with a splash-needle.
AB  - Endoscopic submucosal dissection (ESD) permits the resection of large
      gastrointestinal epithelial neoplasms and neoplasms with submucosal fibrosis in
      an en bloc manner. However, the high frequency of complications accompanying ESD
      and its complex processes suggests that the process requires improvement. A total
      of 22 consecutive patients with gastrointestinal epithelial neoplasms were
      enrolled during a 6-month period to evaluate a novel endosurgical knife for ESD.
      This novel knife is known as the "splash-needle," and it is thin, short needle
      with a water-irrigation function. The technical results revealed that the rates
      of bloc resection and en bloc resection with tumor-free lateral/basal margins (R0
      resection) were 91% (20/22) and 82% (18/22), respectively. There was no
      significant bleeding or perforation during or after ESD. The median operation
      time was 60 minutes (range, 20 to 210). The splash-needle is a promising novel
      endosurgical knife that is useful for less complicated ESD. The accumulation of
      knowledge and cases verifying its usefulness is necessary, and a study comparing
      the knife with first-generation endosurgical knives is also warranted.

PMID- 19098668
TI  - Percutaneous transhepatic cyst drainage as a "bridge procedure" to definitive
      treatment of perforated choledochal cysts: a case report.
AB  - Perforated choledochal cysts are rare. Traditionally, they have been managed by
      primary T-tube choledochostomy and interval cystectomy with hepaticojejunostomy.
      We present here our recent experience with a case of perforated choledochal cyst,
      which was managed with preoperative percutaneous transhepatic cyst drainage,
      followed by definite surgery for choledochal cyst, cyst excision, and
      reconstruction with Roux-en-y hepaticojejunostomy. Preoperative percutaneous cyst
      drainage seems to be useful and effective in managing complicated choledochal
      cysts. The procedure garners time for patients' general condition and laboratory
      findings to improve to the extent that general surgery can be performed.

PMID- 19098669
TI  - Laparoendoscopic evaluation and treatment of massive pneumoperitoneum occurring 1
      year after gastrostomy tube removal.
AB  - A 48-year-old man presented with massive pneumoperitoneum approximately 1 year
      after removal of a gastrostomy tube. A combined laparoscopic and endoscopic
      evaluation was used to identify and resect the gastric perforation at the
      previous gastrostomy site. To our knowledge, this is the longest interval
      reported in the literature for development of pneumoperitoneum after percutaneous
      endoscopic gastrostomy. A laparoendoscopic approach to evaluation and treatment
      of pneumoperitoneum in this setting is described.

PMID- 19098670
TI  - Percutaneous endoscopic gastrostomy for gastric decompression after repeated
      intestinal obstruction after open abdominal surgery.
AB  - In patients with repeated intestinal obstructions after open abdominal surgery,
      aerophagia associated with disturbances in gastrointestinal passage causes the
      accumulation of large amounts of air, resulting in chronic symptoms including
      abdominal pain and distention and consequently malnutrition. We successfully used
      percutaneous endoscopic gastrostomy (PEG) for long-term gastric decompression in
      2 cases with aerophagia. The first case was a 69-year-old Japanese man admitted
      for repeated intestinal obstruction after an appendectomy. After the last surgery
      for intestinal obstruction, the patient experienced repeated abdominal distention
      and anorexia, resulting in weight loss and malnutrition. The second case was a 79
      year-old man complaining of abdominal pain and distention. He had a history of
      resection of the lower pharynx and larynx owing to total laryngectomy and had
      received a permanent tracheostomy. He then underwent surgery for intestinal
      obstruction. Because the patients' abdominal symptoms were unresponsive to
      administration of a peristalsis stimulant and a laxative, we performed PEG to
      deflate the gastrointestinal tract. An abdominal x-ray taken after the PEG
      placement showed the elimination of the gas and a remarkable improvement in the
      gastric dilatation, and the abdominal symptoms soon disappeared. These cases
      highlight the clinical importance and usefulness of PEG for gastric decompression
      in patients with aerophagia associated with repeated intestinal obstruction.

PMID- 19098671
TI  - A devastating complication: duodenal perforation due to biliary stent migration.
AB  - Endoscopic retrograde cholangiopancreatography (ERCP) plays an important
      diagnostic and potentially therapeutic role in the management of a broad range of
      biliary and pancreatic disorders. However, it is an invasive procedure with an
      associated complication rate in the vicinity of 5% to 15% and mortality rate of
      1%. We present an unusual case of a patient who sustained a stent-related
      duodenal perforation after undergoing ERCP. We reviewed the current literature in
      regard to risk factors, etiology, diagnosis, management, and prognosis of ERCP
      related perforations, aiming to provide a brief, updated overview of this
      devastating complication.

PMID- 19098672
TI  - Laparoscopic repair of paraduodenal hernia: comparison with conventional open
      repair.
AB  - Paraduodenal hernia is a congenital internal hernia caused by abnormal
      retroperitoneal fixation of the intestinal mesentery. The management of
      paraduodenal hernia consists of reduction of the herniated intestine and repair
      of the defect. Recently, laparoscopic surgery has been increasingly performed in
      abdominal procedures. To evaluate the feasibility and efficacy of laparoscopic
      repair of paraduodenal hernia, we present our experience in 2 cases of
      laparoscopic repair, compared with 3 other cases treated with conventional open
      repair; all 5 cases were successfully treated. All patients had symptoms of
      intestinal obstruction and were diagnosed by preoperative abdominal computed
      tomography. Two cases were right-sided hernias, and 3 cases were left sided.
      Among them, 2 patients with left-sided paraduodenal hernia underwent laparoscopic
      reduction (LR group) of the herniated small bowel, and the other 3 cases
      underwent open reduction (OR group). In the LR group, the duration of hospital
      stay, time to first flatus, and time to first intake of a soft diet were shorter
      than in the OR group. Thus, with an accurate preoperative diagnosis of
      paraduodenal hernia, laparoscopic surgery may be a feasible and efficient
      procedure, with good postoperative outcomes.

PMID- 19098673
TI  - Cholesterol atheroembolism of the colon can mimic the endoscopic features of
      pseudomembranous colitis.
AB  - The endoscopic features of cholesterol atheroembolism affecting the colon have
      not been extensively described in the literature, owing to the rarity of this
      entity. We report a middle-aged man who presented with hematochezia after recent
      coronary artery bypass graft surgery. Colonoscopy revealed ulcerative skip
      lesions with overlying slough resembling pseudomembranes distal to the transverse
      colon, inconsistent with the initial clinical impression of ischemic colitis. As
      a consequence of continued bleeding with hemodynamic instability, the patient
      underwent an extended low anterior resection with end transverse colostomy.
      Histology revealed cholesterol atheroembolism resulting in patchy ischemic
      ulceration of the colon. Colonic cholesterol atheroembolism can mimic the
      endoscopic features of pseudomembranous colitis.

PMID- 19098674
TI  - Delayed presentation of colonic impalement injury by picture frame glass fragment
      treated using hand-assisted laparoscopic colectomy.
AB  - This is a case of impalement injury with delayed presentation. A 60-year-old man
      experienced a traumatic injury after a fall on top of a broken picture frame,
      which caused a small laceration to his left upper abdominal wall. Sixteen months
      after the injury, he developed a tender left abdominal wall and lower abdominal
      cramping pain. Colonoscopy identified a shard of glass in the left colon. The
      glass presumably impaled his abdominal wall as a result of his previous traumatic
      injury and migrated to the left colon. Laparoscopic surgery was used to safely
      and efficiently remove the impaled glass shard and affected portion of colon.
      Such a case has never been reported.

PMID- 19098675
TI  - A case of endometriosis of the appendix with adhesion to right ovarian cyst
      presenting as intussusception of a mucocele of the appendix.
AB  - Endometriosis of the appendix is rare, and we present a case of endometriosis of
      the appendix with adhesion to right ovarian cyst presenting as intussusception of
      a mucocele of the appendix in a 35-year-old woman with no associated sign of
      endometriosis. Colonoscopy revealed intussusception-like change and mucosal
      defect in the mucosa at the orifice of the appendix. Abdominal computed
      tomography showed a low-density lesion, which seemed to be right ovarian cyst.
      However, as the appendix was located near this site, differentiation between
      ovarian cyst and mucocele of the appendix was difficult. Laparoscopic examination
      disclosed blue berry spots on the Douglas cul-de-sac and right ovarian cyst, and
      the appendix was atrophied and hardened and tightly adhered to the right ovary.
      Laparoscopic appendectomy and partial cecectomy was performed, and on pathologic
      examination, thickening and fibrosis of the muscle layer owing to endometriosis
      were judged to have caused intussusception-like changes.

PMID- 19098676
TI  - Emergency laparoscopic splenectomy for splenic trauma in a Jehovah's Witness
      patient.
AB  - The safety and efficacy of laparoscopic splenectomy in the management of benign
      hematologic diseases is well established. However, most consider the laparoscopic
      approach to splenectomy in trauma patients contraindicated. We present a 76-year
      old Jehovah's Witness who sustained a blunt abdominal trauma, rib fractures, and
      grade III splenic injury. She continued to lose blood, albeit slowly, for which
      she underwent preemptive urgent laparoscopic splenectomy with the use of the red
      cell saver. The operating time was 65 minutes. She was discharged on the 16th
      postoperative day after recovering from fractured ribs with subsequent pulmonary
      atelectasis and basal pneumonia. Whereas the majority of grade I to III splenic
      injuries in adults can be managed conservatively, some 20% will fail and require
      emergency splenectomy for delayed rupture of the spleen. In a Jehovah's Witness
      patient, early splenectomy for injury with the use of red cell saver is advised.
      This may be accomplished laparoscopically in the hemodynamically noncompromised
      patient.

PMID- 19098677
TI  - Atrial fibrillation and transient ischemic attack after endoscopic epinephrine
      injection of a giant polyp.

PMID- 19098678
TI  - CDX2, cytokeratins 7 and 20 immunoreactivity in rectal adenocarcinoma.
AB  - There are limited data regarding CDX2 expression in rectal carcinoma. The
      CK20/CK7 immunoprofile of colorectal adenocarcinoma has been described in
      studies, which have mostly lumped colonic and rectal tumors together. In this
      study, we investigated the diagnostic utility of immunohistochemical stains for
      CK7, CK20, and CDX2 in a series of rectal adenocarcinoma. Fifty-five specimens of
      rectal adenocarcinomas were retrieved and immunostained for CK7 (Dako-M7018),
      CK20 (NovoCastra NCL-L-CK20), and CDX2 (NovoCastra NCL-CDX2). Thirty cases of
      pancreatic adenocarcinoma and 15 cholangiocarcinomas were also studied as a
      comparison group. CK7 was expressed in 12/55 (22%) and CK20 in 48/55 (87%) cases
      of rectal adenocarcinoma. The CK7-/CK20+ immunophenotype was identified in 36/55
      (65%), CK7+/CK20+ in 12/55 (22%), and CK7-/CK20- in 7/55 (13%) rectal
      adenocarcinoma. CDX2 showed moderate-strong positivity in all cases and was not
      related to tumor differentiation. Benign rectal mucosa was available in 37 cases
      and showed the following results: CK7-/CK20+ in 25/37 (67%), CK7+/CK20+ in 8/37
      (22%) and CK7-/CK20- in 4/37 (11%) cases. In pancreatic adenocarcinomas and
      cholangiocarcinomas, 29/45 (64%) were CK7+/CK20+ and 16/45 (36%) were CK7+/CK20-.
      CDX2 was positive in only 3/45 (7%) of these cases; all were pancreatic
      adenocarcinomas. In conclusion, CK7 can be expressed in rectal adenocarcinoma,
      and should not be used as the sole basis for excluding a rectal primary. CDX2 is
      a sensitive marker for rectal origin of adenocarcinoma. It can be helpful in
      cases with metastatic rectal carcinoma, especially those with CK7+/CK20+ or CK20
      /CK7- immunophenotype. In this study, CDX2 expression was not influenced by the
      grade (differentiation) of rectal adenocarcinoma.

PMID- 19098679
TI  - Characterization and applications of a newly developed rabbit monoclonal antibody
      to cytokeratin 7 (CK7) for immunohistochemistry.
AB  - In this paper, we describe the development of a novel rabbit monoclonal
      cytokeratin 7 (CK7) antibody. CK7 is widely used in immunohistochemical tests
      that are commonly performed in histopathology laboratories. Rabbits were
      immunized with a peptide corresponding to C-terminus of CK7. Recombinant
      monoclonal antibodies were developed using proprietary technology. Antibodies
      were screened by enzyme-linked immunosorbent assay against CK7 peptide, and the
      specificity of the antibody was verified by Western blotting on Hela cell lysates
      and by immunohistochemical staining on formalin-fixed paraffin-embedded tissue
      sections. One clone, designated as BC1 was selected and tested on a variety of
      human tissues. Its reactivity was tested and compared with a well-characterized
      mouse monoclonal CK7 antibody OV-TL 12/30 on lung, breast, ovarian, and colon
      cancers, and on a variety of normal tissues. The staining patterns and
      specificity were concordant with mouse monoclonal OV-TL 12/30. The BC1 clone,
      however, showed superior staining to OV-TL 12/30 in terms of intensity and
      staining of debris. CK7 combined with CK20 or CDX2 and TTF1 is a common panel
      used in histopathology laboratories in discrimination between primary
      adenocarcinomas and metastatic lung adenocarcinomas from colonic origin. We then
      developed a 4-step double stain (multiplex) assay by combining CDX-2 with CK7 in
      an antibody cocktail and tested the efficacy on lung, breast, and colon cancers.
      Results showed that this novel antibody can be used as a single component and/or
      in combination with CDX2 and TTF1 in applications for diagnostic pathology.

PMID- 19098680
TI  - An alternative and reliable real-time quantitative PCR method to determine
      HER2/neu amplification in breast cancer.
AB  - The overexpression of HER-2/neu is an independent prognostic factor of clinical
      outcome of breast cancer, therefore determination of HER-2/neu status is now an
      integral part of the clinicopathologic workup. The ways of measuring the copy
      number of the HER-2/neu gene in tumor cells comprise in situ hybridization
      techniques and real-time polymerase chain reaction (PCR). Quantitative real-time
      PCR is a relatively new technique for assessing HER-2/neu gene amplification with
      high sensitivity. However, the HER-2/neu Quantification Kit developed by Roche
      designed for a LightCycler 1.5 platform had been withdrawn from the commercial
      market; therefore, we were encouraged to design an alternative LightCycler-based
      method that offers the desired level of reliability. One hundred breast cancer
      cases with known HER-2/neu status have been examined with the original Roche
      developed HER-2/neu Quantification kit and the custom real-time PCR assay. The
      newly developed, custom PCR showed sensitivity of 91.43%, specificity of 90.63%,
      and accuracy of 90.91% taking fluorescence in situ hybridization results as the
      end point. We have described a novel real-time PCR technique for the relative
      quantification of the HER2/neu gene on a LightCycler 1.5 platform. We have
      determined that our method is eligible and ideal for the supplement of regular
      fluorescence in situ hybridization reactions, concerning its high sensitivity and
      reliability.

PMID- 19098681
TI  - Lack of immunohistochemical detection of VEGF in prostate carcinoma.
AB  - BACKGROUND: Vascular endothelial growth factor (VEGF) has been implicated in
      tumor angiogenesis and is a potential therapeutic target in prostatic
      adenocarcinoma (PrCa). Immunohistochemical (IHC) analysis has been used to
      demonstrate VEGF expression in PrCa, and in various other tumors including breast
      carcinoma, renal cell carcinoma, hepatocellular carcinoma, and gliomas. Prior
      studies have reported markedly varied VEGF expression in benign prostatic
      hyperplasia (0% to 100%) and PrCa (40% to 100%). The objective of this study was
      to measure VEGF expression in PrCa specimens, using IHC analysis with antibodies
      from different manufacturers and different antigen retrieval techniques. DESIGN:
      Cases were identified from an ongoing study analyzing 1270 cases of PrCa
      diagnosed at various Veterans Health Administration hospitals in the New England
      region during 1991 to 1995. From this study population, 50 cases (including 40
      biopsies, 8 transurethral resections of prostate, and 2 radical resections) were
      selected. In all cases, tissues were fixed in 10% formalin and embedded in
      paraffin. Four different antibodies were used for IHC using indirect peroxidase
      method. For each antibody, different dilutions and antigen retrieval methods
      (steam with ethylene diamine tetra-acetate, steam with low pH, water bath with
      target unmasking fluid, trypsin, proteinase K) were tested. EnVision+ system was
      used to overcome nonspecific staining. Appropriate positive and negative controls
      were used. RESULTS: Using different antibodies, positive staining of varying
      intensity was seen in benign glands, malignant glands, endothelial cells, and
      fibromuscular stroma. Some cases showed cytoplasmic and granular staining in
      prostatic glands. However, the staining disappeared in all cases when EnVision+
      system was used to block nonspecific staining except for focal and minimal
      staining in the endothelial cells. CONCLUSIONS: Our results show that when
      nonspecific staining is blocked, no staining is found for VEGF within the
      prostate, in either benign or malignant glands. The reasons for the granular and
      nonspecific staining are unclear at present. Our study may help to explain
      variable results reported in previous studies, and suggests caution in
      interpreting VEGF expression in studies of PrCa and benign glands.

PMID- 19098682
TI  - Proinflammatory cytokines and receptor activator of nuclear factor kappaB
      ligand/osteoprotegerin associated with bone deterioration in patients with
      Crohn's disease.
AB  - OBJECTIVES: The high incidence of bone disease and the increasing evidence of
      Crohn's disease (CD) bone decline in corticosteroid users and nonusers suggest
      that bone metabolism is affected by inflammatory process. The aim of the study
      was to compare serum levels of proinflammatory cytokines, markers of bone
      turnover and regulatory molecules of osteoclast biogenesis, receptor activator of
      nuclear factor kappaB-ligand (RANKL) and osteoprotegerin (OPG), between naive and
      long-standing CD patients. METHODS: The study included 95 CD patients, 15 of them
      with newly diagnosed and previously untreated CD. The spine and hip bone mineral
      density was measured by dual-energy X-ray absorptiometry. Biochemical markers
      were determined by immunoassay. RESULTS: Osteopenia was recorded at diagnosis in
      53% of naive patients and osteoporosis was found in 26% of long-standing CD
      patients. The newly diagnosed patients showed correlation between TNF-alpha and
      soluble RANKL (sRANKL) (r=0.5; P=0.04), and this positive relationship
      characterized the study population as a whole (r=0.3; P=0.003). Analysis of the
      OPG and sRANKL relationship showed absence of correlation in patients with
      healthy skeleton, whereas an inverse correlation was found in those with
      osteopenia (r=-0.31; P=0.033) and osteoporosis (r=-0.48; P=0.028). In naive
      patients with reduced T score, the correlation between sRANKL and OPG was highly
      inverse (r=-0.8; P=0.02) and these patients were characterized by lower BMI,
      significantly higher level of proinflammatory cytokines, elevated C-reactive
      protein, and increased activity of free sRANKL and OPG. CONCLUSION: Bone disease
      that accompanies CD at diagnosis suggests that bone metabolism is affected by the
      underlying inflammatory process per se, as probably confirmed by our finding of
      the central proinflammatory cytokine TNF-alpha being strongly associated with the
      osteoclastogenic mediator RANKL, and inversely with bone density.

PMID- 19098683
TI  - Three-generation familial visceral myopathy with alpha-actin-positive inclusion
      bodies in intestinal smooth muscle.
AB  - We report the clinical and histopathologic findings of a family with 7 affected
      members in 3 generations suffering from autosomal dominant visceral myopathy. All
      patients presented with chronic intestinal pseudo-obstruction affecting
      especially the entire small bowel. Histologic abnormalities involved intestinal
      smooth muscle, with degeneration and fibrosis of the muscularis propria. In
      addition, the inner circular layer of the muscularis propria contained alpha
      smooth muscle actin-positive and, in more advanced disease, also periodic acid
      Schiff-positive inclusion bodies. The inclusions were invisible in routine
      hematoxylin-eosin-stained sections, but were visible in immunohistochemical
      stainings for alpha-smooth muscle actin. No abnormality was evident in muscularis
      mucosae or in blood vessels, and the findings remained unidentified in mucosal
      biopsy specimens. To our knowledge, this is the first reported alpha-actin
      positive inclusion body finding in familial visceral myopathy.

PMID- 19098684
TI  - The APRI and the RVR.

PMID- 19098685
TI  - Severe hepatocellular injury with apoptosis induced by a hepatitis C polymerase
      inhibitor.
AB  - GOALS: To describe the mechanisms of severe hepatocellular injury with apoptosis
      in 2 patients receiving hepatitis C virus (HCV)-796. BACKGROUND: HCV-796 is a
      hepatitis C polymerase inhibitor approved by the US Food and Drug Administration
      for a phase 2 study of the treatment of hepatitis C in combination with PEG
      Interferon and ribavirin. RESULTS: The injury occurred after more than 12 weeks
      of treatment, with a >20-fold increase in serum alanine aminotransferase and
      aspartate aminotransferase, and a marked increase in total (and direct) bilirubin
      in the absence of cholestasis. There was no evidence of autoimmune or viral
      hepatitis. Involvement of the mitochondrial apoptotic pathway was demonstrated by
      (1) release of cytochrome C into the cytosol; (2) association of cytochrome C
      with apoptotic protease activating factor-1 in the cytosol; (3) activation of
      initiator caspase 9; (4) activation of effector caspase 3; (5) increased serum
      caspase-3 cleaved cytokeratin-18 peptide; (6) nuclear fragmentation; (7)
      mitochondrial structural abnormalities; (8) expression of light chain 3 B, an
      indicator of autophagy; (9) probable autophagy of mitochondria by autophagosomes;
      and (10) probable phagocytosis of apoptotic hepatocytes by activated macrophages.
      Immunoglobulin G immune complexes were identified in the hepatocytes and
      localized to the endoplasmic reticulum and Golgi of these patients after the drug
      induced liver disease, reflecting a primary or secondary target. Hepatitis C
      treatment was discontinued at weeks 15 and 19 in patients 1 and 2, respectively.
      After more than 6 months off the medication, both patients normalized the serum
      alanine aminotransferase, aspartate aminotransferase, and total bilirubin with
      undetectable HCV RNA. CONCLUSIONS: HCV-796 may cause severe hepatocellular injury
      and apoptosis, with a marked immune reaction in susceptible patients.

PMID- 19098687
TI  - Pharmacokinetics of dehydroepiandrosterone and its metabolites after long-term
      oral dehydroepiandrosterone treatment in postmenopausal women.
AB  - OBJECTIVE: Some postmenopausal women use over-the-counter dehydroepiandrosterone
      because of its purported beneficial effects. Although without major inherent
      androgenic activity, it is metabolized to potent androgens and estrogens. We
      investigated the pharmacokinetics of dehydroepiandrosterone and its relevant
      metabolites after prolonged treatment of postmenopausal women with 25 mg/d of
      dehydroepiandrosterone. METHODS: Twenty healthy postmenopausal women were
      randomized to either 25 mg/d of dehydroepiandrosterone or placebo for 6 months.
      Frequent blood samples were obtained over 24 hours on day 1 and after 3 and 6
      months. RESULTS: Mean baseline androgen levels at day 1 and month 3 in the
      treated group (seven evaluable women) were the following: dehydroepiandrosterone,
      1.82 and 3.56 ng/mL; dehydroepiandrosterone sulfate, 0.96 and 3.37 microg/mL; 5
      androstene-3beta,17beta-diol, 0.32 and 0.66 ng/mL; androstenedione, 0.50 and 0.86
      ng/mL; testosterone, 17.9 and 28.7 ng/dL; dihydrotestosterone, 6.91 and 17.4
      ng/dL; and 3alpha-androstanediol glucuronide, 2.66 and 10.7 ng/mL, respectively;
      these increases were significant. Small changes (-6% to 16%) were observed from
      month 3 to month 6. Nonsignificant increases were observed in baseline estrone
      and estradiol levels and in Cmax and AUC0-24h values for the androgens and
      estrogens from day 1 to months 3 and 6 of treatment. Sex hormone-binding globulin
      levels were unchanged, but free testosterone increased significantly from day 1
      to month 3. Baseline hormone levels did not increase in the placebo group (six
      evaluable women). Changes in baseline values over time differed significantly
      between the groups for all hormones except estrone and estradiol. CONCLUSIONS: In
      postmenopausal women treated orally with a commonly available dose of
      dehydroepiandrosterone, the daily exposure (AUC) of dehydroepiandrosterone and
      its principal androgenic metabolites was found to be similar during 6 months of
      treatment despite increased serum baseline concentrations of these androgens.

PMID- 19098686
TI  - Increased prevalence of gastroesophageal reflux symptoms in obese children
      evaluated in an academic medical center.
AB  - GOALS: To test the hypothesis that obese children are at higher risk of having
      gastroesophageal reflux symptoms compared with nonobese children. STUDY: In this
      prospective study, 236 obese children (age: 7 to 16 y) were interviewed using a
      standard questionnaire for reflux symptoms and a reflux symptom score was
      calculated. Obesity was defined as body mass index (BMI) greater than 95th
      percentile for age and sex. One hundred and one age-matched and sex-matched
      children with BMI between 5th and 95th percentile served as controls. Demographic
      data were collected in all children. We compared prevalence rates of a reflux
      symptom score and other symptoms between the 2 groups. RESULTS: A prevalence rate
      of a positive reflux symptom score (13.1%) was significantly higher in obese
      children than in the control group (2%) (odds ratio: 7.3, 95% CI: 1.7-31).
      Obesity remained as the only significant predictor for a positive reflux symptom
      score after controlling for other variables such as age, sex, race, and caffeine
      exposure (adjusted odds ratio: 7.4, 95% CI: 1.7-32.5). A positive reflux symptom
      score increased significantly from 2% in the control group to 11.7% in 196 obese
      children to 20% in 40 severely obese children (with BMI z-score >2.7).
      CONCLUSIONS: Obese children (age: 7 to 16 y) are at higher risk of having reflux
      symptoms compared with the control group. This risk is independent of age, sex,
      or race and increases with higher BMI.

PMID- 19098688
TI  - The effect of Pueraria mirifica on cytologic and urodynamic findings in
      ovariectomized rats.
AB  - OBJECTIVE: To evaluate the effect of Pueraria mirifica on vaginal and urethral
      cytology, bladder pressure and capacity, residual urine, and leak point pressure
      in ovariectomized rats. METHODS: Seventy-two adult, ovariectomized, female
      Sprague-Dawley rats were placed into one of four groups: control, estradiol, or
      100 or 1,000 mg/kg of Pueraria mirifica (PM-100 and PM-1000, respectively). The
      vaginal and urethral smears were checked after 30 days of ovariectomy at
      pretreatment and at day 28 of treatment.A single cystometry, defined as the
      micturition interval, filling pressure, threshold pressure, micturition pressure,
      and voided volume, was performed. Peak bladder pressure was calculated for each
      leak point pressure measured at half bladder capacity by slowly and manually
      increasing abdominal pressure until a leak occurred, at which point external
      pressure was rapidly released. Leak point pressure was tested three times per
      rat. RESULTS: After 28 days of treatment, the estradiol, PM-100, and PM-1000
      groups had significantly higher numbers of vaginal and urethral superficial cells
      compared with the control group (P < 0.05). Regarding the urodynamic parameters,
      the threshold pressure, micturition pressure, and leak point pressure were higher
      in the estradiol, PM-100, and PM-1000 groups compared with the control group (P <
      0.05). The control, PM-100, and PM-1000 groups had the same values for
      micturition interval, bladder capacity, voided volume, and residual volume (P >
      0.05) but lower values compared with the estradiol group (P < 0.05). CONCLUSIONS:
      Pueraria mirifica 100 and 1,000 mg/kg/day showed an estrogen-like effect on the
      vaginal and urethral epithelium of ovariectomized rats. They did not change
      bladder capacity and residual urine volume but increased leak point pressure
      according to urodynamic study.

PMID- 19098689
TI  - Frequency of syphilis testing in HIV-infected patients: more and more often.

PMID- 19098690
TI  - Seroprevalence and risk factors for herpes simplex virus infection in a
      population of HIV-infected patients in Canada.
AB  - OBJECTIVE: To determine the seroprevalence of herpes simplex virus infection in a
      population of HIV-infected individuals in Canada. METHODS: HIV-infected patients
      attending 5 infectious disease clinics for follow-up care were approached to
      participate in the study. After informed consent was obtained, subjects completed
      a questionnaire documenting HIV-risk behavior, duration of infection, history of
      oral and/or genital herpes, and treatment for HIV and/or genital herpes. Blood
      for HSV type-specific serology was drawn and tested by enzyme-linked
      immunosorbent assay (Focus Diagnostics HerpeSelect HSV-1, HSV-2 enzyme-linked
      immunosorbent assay IgG). Equivocal samples were repeated and any discrepant
      results were resolved with Western blot. RESULTS: Six hundred twenty-nine HIV
      infected individuals participated. The mean age was 43.9 years, 74.7% were
      Canadian born and 72.3% were men. The majority of foreign-born subjects were
      black (endemic) and women. The seroprevalence of HSV-1 and HSV-2 was 78.1% and
      54.6%, respectively. Women were 2.7 times more likely to be HSV-2 seropositive,
      non-Canadian-born participants were 2.0 times more likely to be HSV-2
      seropositive, and nonwhite subjects were 3.2 times more likely to be
      seropositive. Men who had sex with other men had the lowest seroprevalence of HSV
      2. Only 30.3% of HSV-2 positive subjects reported a history of genital herpes.
      CONCLUSIONS: A significant proportion of HIV-infected subjects attending 5
      infectious disease clinics in Canada are coinfected with HSV. Routine type
      specific HSV-2 testing should be introduced to direct education regarding
      symptoms, signs, and transmission reduction of genital herpes and perhaps
      ultimately HIV-1. Knowledge of HSV serostatus would also provide an opportunity
      to consider antiviral therapy.

PMID- 19098691
TI  - Do general practices which provide an acupuncture service have low referral rates
      and prescription costs? A pilot survey.
AB  - BACKGROUND: Studies by individual acupuncture practitioners have given an
      indication that offering acupuncture in primary care may reduce the need for
      referral to secondary care and reduce the costs of prescriptions. It would be
      informative to find out whether these findings can be supported by data from
      other practices. The aim of this study was to test the feasibility of surveying
      national data on referrals and prescribing. METHODS: Three primary care trusts
      (PCTs) were selected, and all practices within each trust were sent an email
      asking whether any member of the primary care team offered acupuncture, and if so
      how many appointments per week. Data on rates of referral to orthopaedic,
      physiotherapy, pain and rheumatology clinics were then sought from the PCT, both
      for the practices offering acupuncture and for the PCT as a whole. Similarly,
      data on costs of prescriptions for non-steroidal (NSAID) and non-opioid analgesic
      drugs were obtained from the Prescription Pricing Authority. RESULTS: Out of the
      109 practices surveyed, a total of 14 (13%) offered acupuncture services to some
      extent. There was wide variation in provision between the different PCTs. The
      eight practices which offered at least one appointment per week for every 2000
      registered patients were included in the analysis. The mean values (and SDs) for
      the three PCTs and for the eight acupuncture practices, respectively, were as
      follows: for referral to various clinics: orthopaedic 32.3 (16.2) and 27.4
      (10.87); pain clinic 1.6 (1.3) and 2.8 (1.6); physiotherapy 13.4 (14.5) and 29.5
      (10.0); and rheumatology 4.7 (2.3) and 6.4 (3.0). The mean values for costs of
      non-opioid analgesics were pound1820 ( pound442) and pound2008 ( pound762); and
      for NSAIDs were pound4148 ( pound269) and pound4476 ( pound1366), respectively.
      There were no trends towards a reduction of clinic referral or prescription
      costs. CONCLUSIONS: We have conducted the first survey of the effects of
      provision of acupuncture in UK general practice, using data provided by the NHS,
      and uncovered a wide variation in the availability of the service in different
      areas. We have been unable to demonstrate any consistent differences in the
      prescribing or referral rates that could be due to the use of acupuncture in
      these practices. The wide variation in the data means that if such a trend
      exists, a very large survey would be needed to identify it. However, we
      discovered inaccuracies and variations in presentation of data by the PCTs which
      have made the numerical input, and hence our results, unreliable. Thus the
      practicalities of access to data and the problems with data accuracy would
      preclude a nationwide survey.

PMID- 19098692
TI  - Intramuscular and periosteal acupuncture in patients suffering from chronic
      musculoskeletal pain - a controlled trial.
AB  - BACKGROUND: Periosteal acupuncture has shown promising results in clinical
      practice. The aim was to compare three patient groups: one with intramuscular
      acupuncture, one with periosteal acupuncture, and a third information control
      group, with respect to clinically relevant pain relief, physical functioning and
      intake of analgesics in patients with chronic musculoskeletal pain in the neck or
      low back or both. We reported the psychological changes in these patients in a
      previous issue of this journal. METHODS: 144 consecutive patients with
      nociceptive pain for >3 months, aged 18-70 years were alternately allocated to:
      intramuscular acupuncture (n=59); periosteal acupuncture (n=55); or control group
      with information only (n=30). All patients were encouraged to stay active.
      Acupuncture was administered with eight treatments during five weeks, and two
      optional additional treatments after one month. Pain was estimated with a daily
      VAS in a pain diary and with an average weekly pain score. Clinically relevant
      pain relief was defined as at least a 30% decrease from the initial value.
      Physical functioning was evaluated with Disability Rating Index. All estimations
      were performed prior to treatment, one week after, and one, three and six months
      after treatment. RESULTS: There were no differences between the effects of the
      two acupuncture methods. There were differences between each of the two
      acupuncture groups compared with the control group on all test occasions up to
      one month after treatment with respect to the pain diary and one week after
      treatment with respect to pain last week (P<0.05). Pain relief as measured by a
      pain diary was obtained in 29 patients in the intramuscular acupuncture group, 25
      in the periosteal acupuncture group, and 5 patients in the control group. Six
      months after treatment, 46% of the intramuscular acupuncture patients and 45% of
      the periosteal acupuncture patients had obtained pain relief in terms of the pain
      diary. The corresponding figure for pain last week was 29% in each group.
      CONCLUSIONS: Periosteal pecking was no more effective than standard intramuscular
      acupuncture, but both were more effective than information only.

PMID- 19098693
TI  - A placebo acupuncture needle with potential for double blinding - a validation
      study.
AB  - BACKGROUND: The double blind, non-penetrating placebo needle is effective in
      masking patients who are not informed that they may receive a placebo needle. In
      this study, we aimed to examine whether such needles are effective in masking
      subjects who have been so informed. METHODS: One hundred and fourteen informed,
      consenting, healthy volunteers were recruited. An experienced acupuncturist
      applied one of the following needle pairs - penetrating/non-penetrating, non
      penetrating/non-penetrating, penetrating/penetrating - randomly at bilateral TE5
      points in subjects who were informed that they would receive either a non
      penetrating or a penetrating needle. After the application of a pair of needles,
      the subjects reported for each arm on whether they identified the needle as non
      penetrating or penetrating. The patients also rated skin penetration/penetration
      like pain and the deep dull pain (de qi) associated with the needle application
      on a visual analogue scale (VAS). The chi squared goodness of fit test was used
      to determine the probability of the number of correctly and incorrectly
      identified needles. Statistical comparisons for VAS scores for skin penetration
      pain and de qi were made using Mann-Whitneys U test. RESULTS: Of the 114 non
      penetrating needle applications, the subjects identified 64 incorrectly and 50
      correctly, fitting a probability of 0.5 (chi2=1.72, P=0.19). Most interestingly,
      the subjects identified 36 (32%) of 114 penetrating needle applications
      incorrectly. Skin penetration/penetration-like pain and de qi scores did not
      differ significantly (P=0.87 and P=0.17, respectively) between the 114 non
      penetrating and 114 penetrating needles. CONCLUSION: The non-penetrating placebo
      needle was effective in masking fully informed subjects. When used together with
      the matched penetrating needle, it has potential for use in double blind (patient
      and practitioner blind) studies.

PMID- 19098694
TI  - Perforation of the median nerve with an acupuncture needle guided by ultrasound.
AB  - In an experiment on one of the authors, we used ultrasound to visualise an
      acupuncture needle completely perforating the median nerve at the acupuncture
      point PC6. During this procedure only a slight sensation occurred, and no pain.
      We conclude that, in individual cases, the median nerve might be perforated
      without causing pain or neurological problems.

PMID- 19098695
TI  - Acupuncture for preconditioning of expectancy and/or Pavlovian extinction.
AB  - Both specific and non-specific factors, as well as the therapist, may play a role
      in acupuncture therapy. Recent results suggest that verum acupuncture has
      specific physiological effects and that patients expectations and belief
      regarding a potentially beneficial treatment modulate activity in the reward and
      self-appraisal systems in the brain. We suggest that acupuncture treatment may
      partly be regarded and used as an intervention that preconditions expectancy,
      which results in both conditional reflexes and conditioning of expected reward
      and self-appraisal. If so, acupuncture should preferably be applied before the
      start of the specific treatment (drug or behavioural intervention which is given
      with the intention of achieving a specific outcome) to enhance the specific and
      non-specific effects. This hypothesis is further supported by the suggestions
      that acupuncture may be viewed as a neural stimulus that triggers Pavlovian
      extinction. If this is the case, acupuncture should preferably be applied
      repeatedly (ie in a learning process) before the start of the specific treatment
      to initiate the extinction of previous unpleasant associations like pain or
      anxiety. Our clinical data suggest that acupuncture may precondition expectancy
      and conditional reflexes as well as induce Pavlovian extinction. Based on the
      above we suggest that acupuncture should be tried (as an adjunct) before any
      specific therapy.

PMID- 19098696
TI  - The Emperors sham - wrong assumption that sham needling is sham.
AB  - During the last five years a large number of randomised controlled clinical
      trials (RCTs) have been published on the efficacy of acupuncture in different
      conditions. In most of these studies verum is compared with sham acupuncture. In
      general both verum and sham have been found to be effective, and often with
      little reported difference in outcome. This has repeatedly led to the conclusion
      that acupuncture is no more effective than placebo treatment. However, this
      conclusion is based on the assumption that sham acupuncture is inert. Since sham
      acupuncture evidently is merely another form of acupuncture from the
      physiological perspective, the assumption that sham is sham is incorrect and
      conclusions based on this assumption are therefore invalid. Clinical guidelines
      based on such conclusions may therefore exclude suffering patients from valuable
      treatments.

PMID- 19098697
TI  - Acupuncture for locomotor disabilities in a South American red-footed tortoise
      (Geochelone carbonaria) - a case report.
AB  - The literature contains numerous reports of the effect of acupuncture on domestic
      or experimental animals, but only a few involving wild animals. This paper
      reports on acupuncture treatment for locomotor disabilities in a South American
      red-footed tortoise (Geochelone carbonaria, SPIX, 1824), an endangered land
      tortoise found in Brazils Cerrado region. The animal was captured and kept in an
      aquatic pen, subsequently developing respiratory symptoms and locomotor
      disabilities. The respiratory symptoms resolved in response to antibiotic
      treatment. However, despite the use of nutritional supplements, the motor
      symptoms remained unchanged. After 16 months, the tortoise was given six
      acupuncture sessions. No other changes were made to its environment or
      management. The location of the acupuncture points was transposed from canine
      charts. After acupuncture, the animals motor functions, which had remained
      unchanged during the preceding 16 months, were restored, enabling it to eat and
      walk unaided. The improvement persisted during 18 months follow up. The
      transposition of acupuncture points from canine charts is a viable alternative
      for chelonians.

PMID- 19098698
TI  - Prolonged ocular hypotension: would ciliary tissue transplantation help.
AB  - AIMS: Ocular hypotony and phthisis bulbi from persistent fistulae, ciliochoridal
      detachments, or inflammation, that cannot be treated currently. However, complete
      shutdown of the ciliary epithelium is rare. Secreting, transplanted ciliary
      tissue could restore the IOP to a level where further visual damage would not
      occur or even be reversed. METHODS: Allografts of ciliary epithelium and its
      substrate were placed on to the surface of the iris of normal albino rabbits. The
      progress of the transplanted tissue was followed in the untreated animals, those
      who had been immunosuppressed and those who had been immunosuppresed together
      with cold whole body perfusion for up to 55 days. Changes were assessed by slit
      lamp observation, luconyl blue staining, fluoresceine angiography, and these were
      compared with the histology and electron microscopic appearances. RESULTS:
      Transplants survived the period of ischaemia in the anterior chamber. They
      started to be revascularised within 4 days and were completely revascularised in
      12 days. Untreated animals showed classical rejection phenomena. However, the
      ciliary epithelial tissue in those animals who were immunosuppressed and had been
      subjected to whole body perfusion remained normal and were secreting aqueous, as
      judged by the histological and electron microscopic appearances. CONCLUSIONS:
      Perfused allografts of ciliary tissue will survive in the normal anterior chamber
      of the immunosuppressed rabbit, and the electron microscopic evidence indicates
      that the tissue is producing aqueous. If this can be shown to be adequate in the
      damaged eye, then ciliary transplantation could be a valuable tool in the
      management of severe intractable hypotony.

PMID- 19098699
TI  - Influence of microglia on retinal progenitor cell turnover and cell replacement.
AB  - Microglia within the retina are continually replaced from the bone marrow and are
      the resident myeloid-derived cells within the retina. Throughout life, microglial
      function is conditioned by the microenvironment affording immunomodulation to
      control inflammation as well as functioning to enable normal development and,
      during adulthood, maintain normal retinal function. In adulthood, recent evidence
      supports the concept that the retina continues to replace cells to maintain
      optimal function. Although in some cases after injury, degeneration, or
      inflammation there remains an inextricable decline in visual function inferring a
      deficit in cell replacement, the deficit could be explained by microglial cell
      activation influencing the ability of either retinal progenitor cells or
      recruited progenitor cells to integrate and differentiate appropriately. Myeloid
      cell response differs depending on insult: it is evident that during inflammation
      microglia and the infiltrating myeloid cell function are conditioned by the
      cytokine environment. Indeed, modulating myeloid cell function therapeutically
      suppresses disease in experimental models of autoimmunity, whereas in non
      inflammatory models microglia have little or no effect on the course of
      degeneration. The extent of myeloid activation can help determine retinal
      progenitor cell turnover. Retinal progenitor cells may be isolated from adult
      human retina, which, albeit limited, display mitotic activity and can
      differentiate. Microglial activation secreting IL-6 limits progenitor cell
      turnover and the extent to which differentiation to post-mitotic retinal cells
      occurs. Such experimental data illustrate the need to develop methods to
      replenish normal retinal myeloid cell function facilitating integration, either
      by cell transplantation or by encouraging retinal progenitor cells to recover
      retinal function.

PMID- 19098700
TI  - Characterization of dendritic cell phenotype in allergic conjunctiva: increased
      expression of Fc(epsilon)RI, the high-affinity receptor for immunoglobulin E.
AB  - PURPOSE: Dendritic cells (DCs) express the high-affinity receptor for IgE
      (Fc(epsilon)RI) on their surface, which may enhance their ability to capture and
      internalize antigens for presentation to T-lymphocytes. The aim of this study was
      to determine if expression of Fc(epsilon)RI(+) DCs is increased in the
      conjunctivae of vernal keratoconjunctivitis (VKC) patients compared with those of
      normal controls. METHODS: Conjunctival biopsies were obtained from non-atopic and
      VKC patients. Double immunohistochemical staining was carried out using
      antibodies against Fc(epsilon)RI and the CD1a antigen, a DC marker. The double
      positive cells were counted in five representative fields of view for each
      conjunctival sample. RESULTS: Fc(epsilon)RI(+) CD1a(+) cells were present in
      significantly higher numbers in VKC conjunctivae compared with normal controls
      (mean cell count of 21.3 in VKC vs5.0 in controls, P<0.005). In normal patients
      the Fc(epsilon)RI-expressing DCs tended to be confined to the epithelial layer or
      the superficial substantia propria, but in the VKC samples these Fc(epsilon)RI(+)
      cells were mainly concentrated in the deeper substantia propria. CONCLUSIONS:
      Fc(epsilon)RI(+) DC numbers are elevated in the conjunctivae of VKC patients, a
      finding consistent with the results of other studies focusing on atopic
      conditions. Elevated expression of Fc(epsilon)RI on DCs would facilitate antigen
      presentation and enhance T-cell priming, thereby contributing to ocular symptoms.

PMID- 19098701
TI  - Monocular diplopia induced by posterior chamber intraocular lens in a patient
      with peripheral laser iridotomy: a case report.

PMID- 19098702
TI  - Transplantation prospects for the inner retina.
AB  - Transplantation of stem or progenitor cells is an attractive new approach for
      treating neurodegenerative conditions of the central nervous system, which aims
      to protect or replace neurons and improve function. Proof of principle has
      already been shown in the retina that photoreceptors may be replaced by
      transplantation of neural progenitor cells. However, the task of retinal ganglion
      cell replacement is much more complex, as new cells will need to establish
      complex connections within the retina and also extend axons to precise targets in
      the brain. Although progress has been made in this field, it is likely that
      neuroprotective clinical applications will be established more quickly. Our
      laboratory has focused on the intraocular transplantation of cells to treat inner
      retinal disease, either by neuronal replacement or neuroprotection of existing
      cells. We have investigated the efficacy and effects of transplanting a variety
      of cell types, including human Muller stem cells (MIO-M1), oligodendrocyte
      precursor cells (OPCs), and bone marrow-derived mesenchymal stromal cells (MSCs)
      in a rat model of experimentally induced glaucoma. We also have developed and
      characterized a novel in vitro organotypic retinal explant culture system for
      exploring the methods of enhancing the efficacy of cell transplantation for the
      inner retina. In this review, we discuss the potentially beneficial effects of
      intraocular cell injections, identify current shortcomings of retinal stem cell
      therapy, and suggest directions for future research.

PMID- 19098703
TI  - Current and future prospects for optoelectronic retinal prostheses.
AB  - There has been accelerating progress in the development of retinal prosthesis
      systems designed to partially restore vision to people with retinitis pigmentosa
      or macular degeneration. Current retinal prostheses can be divided into two
      types: those that receive power and information from passive or active
      photodiodes (optoelectronic systems) and those based on multielectrode arrays
      powered by cables or transcutaneous telemetry systems. Currently, four research
      groups have ongoing chronic implantation clinical studies, and two of these
      groups plan to have commercial retinal prosthesis systems available within the
      next 2 years. This paper reviews the development and current status of the most
      significant international retinal prosthesis research groups and discusses future
      prospects and issues associated with their retinal prosthesis systems.

PMID- 19098705
TI  - Cystoid foveal oedema in symptomatic inner lamellar macular holes.
AB  - PURPOSE: Inner lamellar macular hole (LMH) was considered a relatively risk-free
      condition that rarely progresses or worsens. Nowadays, at the optical coherence
      tomography (OCT) era, increasing evidence seems to position it differently. The
      aim of the study was to describe morphologic abnormalities associated with
      symptomatic LMH using OCT that may explain reduced visual acuity in these
      patients. METHODS: In a retrospective study on consecutive symptomatic patients
      with LMH, OCT scans were compared with normal controls. Analysis was referred to
      LMH-associated abnormalities at the residual fovea, mainly cystoid spaces that
      manifested as cystoid foveal oedema. RESULTS: A total of 22 eyes of 20 patients
      (mean age, 68 years; range, 22-94) were included in the study. Best-corrected
      visual acuity ranged from 6/9 to 6/120. Cystoid foveal oedema that contained
      cystoid spaces of various sizes was found in 21 (95%) of eyes; an intraretinal
      split was seen in 18 eyes (82%) and epiretinal membrane was detected in 16 eyes
      (73%). CONCLUSIONS: The appearance of cystoid oedema at the residual fovea in
      symptomatic LMHs may explain in part a reduced visual acuity and/or
      metamorphopsia. The old notion on the low incidence of LMH progression may
      probably be related in part to (a) lower diagnostic accuracy before OCT was
      available and to (b) the already spontaneously peeled inner limiting membrane.
      Further studies are required to verify these observations, which may merit
      clinical and surgical considerations.

PMID- 19098706
TI  - The changes in corneal biomechanical parameters after phototherapeutic
      keratectomy in eyes with granular corneal dystrophy.
AB  - PURPOSE: To assess corneal biomechanical changes in eyes undergoing
      phototherapeutic keratectomy (PTK) and to investigate the relationship of PTK
      with corneal thickness. METHODS: We examined 36 eyes of 23 patients undergoing
      PTK for the treatment of granular corneal dystrophy (GCD). Corneal hysteresis
      (CH) and corneal resistance factor (CRF) were measured with an Ocular Response
      Analyzer before and 3 months after surgery. We also investigated the
      relationships between corneal biomechanical parameters and central corneal
      thickness before and after surgery. RESULTS: The CH was significantly decreased
      from 10.2+/-2.2 to 8.7+/-1.8 mm Hg after PTK (Wilcoxon signed-rank test,
      P<0.001), as was the CRF, from 10.3+/-2.0 to 8.5+/-1.8 mm Hg (P<0.001). We found
      a significant correlation between both CH and CRF and the central corneal
      thickness before surgery (Pearson correlation coefficient r=0.37, P=0.03 for CH,
      r=0.51, P=0.002 for CRF) and 3 months after surgery (r=0.54, P=0.001 for CH,
      r=0.74, P<0.001 for CRF). CONCLUSIONS: PTK induces a significant decrease in the
      biomechanical parameters of the cornea. The corneal thickness may play some role
      in corneal biomechanics even in eyes with GCD.

PMID- 19098704
TI  - Limbal stem cell transplantation: new progresses and challenges.
AB  - Patients with limbal stem cell deficiency (LSCD) suffer from photophobia and a
      severe loss of vision uncorrectable by conventional PKP. This literature review
      shows that new strategies can be formulated for treating LSCD. Early
      cryopreserved amniotic membrane transplantation (AMT) as a temporary biological
      bandage with sutures or with sutureless ProKera in the acute stage of chemical
      burn and Stevens-Johnson syndrome prevents the occurrence of LSCD by preserving
      and expanding the remaining limbal epithelial stem cells. Similarly, remaining
      limbal stem cells can also be expanded in corneal surfaces with partial or nearly
      total LSCD if corneal pannus is removed and AMT is performed as a graft with or
      without sutures by the use of fibrin glue. Moreover, AMT as a temporary bandage
      and a graft using fibrin glue can also facilitate corneal surface reconstruction
      by reducing the size of a conjunctival limbal autograft (CLAU) to one 60 degrees
      graft for unilateral total LSCD as well as promote the success of a keratolimbal
      allograft (KLAL) for bilateral total LSCD. The latter success is further dictated
      by effective systemic immunosuppression and by measures to restore the ocular
      surface defenses, suppress conjunctival inflammation, and correct cicatricial
      complications so that a stable tear film can be maintained before surgery. This
      review also summarizes recent findings and outlines future challenges that we
      need to overcome in squamous metaplasia, that is, another major type of ocular
      surface failure.

PMID- 19098707
TI  - Prospects for genetic modulation of corneal graft survival.
AB  - Irreversible immunological rejection is the major cause of clinical corneal graft
      failure. Ex vivo gene therapy directed at the donor cornea has been shown to
      prolong orthotopic corneal allograft survival significantly in experimental
      animal models including the mouse, rat, rabbit, and sheep. Transgenes effective
      in prolonging corneal graft survival include immunomodulatory cytokines and
      cytokine receptors, an inhibitor of neovascularisation, a blocker of antigen
      presenting cell-T cell co-stimulation, nerve growth factor, a dominant negative
      regulator of apoptosis, and the enzyme indoleamine 2,3-dioxygenase. Although many
      viral and non-viral vectors have been shown to transduce the corneal endothelium
      efficiently, allograft survival has so far been prolonged only following
      transduction of the donor cornea with adenoviral and lentiviral vectors. The
      degree of graft prolongation, although promising, is still insufficient for
      immediate translation to the clinic. Increasing the time that the therapeutic
      gene is expressed in the eye with an integrative, non-immunogenic viral vector is
      likely to be one way to achieve long-term graft survival. Simultaneous targeting
      of multiple pathways of graft rejection with more than one transgene is likely to
      be another. We suggest that the use of an adeno-associated viral or lentiviral
      vector combined with multiple transgenes may provide the key to future clinical
      trials.

PMID- 19098708
TI  - Reply to: Costa DC et al. The use of subconjunctival triamcinolone acetonide
      (SCTA) in the management of corneal endothelial graft rejection.

PMID- 19098709
TI  - Retinal pathology in the fellow eye of patients presenting with wet age-related
      macular degeneration in the index eye.

PMID- 19098711
TI  - RYBP stabilizes p53 by modulating MDM2.
AB  - The mouse double minute 2 (MDM2)-p53 interaction regulates the activity of p53
      and is a potential target for human cancer therapy. Here, we report that RYBP
      (RING1- and YY1-binding protein), a member of the polycomb group (PcG), interacts
      with MDM2 and decreases MDM2-mediated p53 ubiquitination, leading to
      stabilization of p53 and an increase in p53 activity. RYBP induces cell-cycle
      arrest and is involved in the p53 response to DNA damage. Expression of RYBP is
      decreased in human cancer tissues compared with adjacent normal tissues. These
      results show that RYBP is a new regulator of the MDM2-p53 loop and that it has
      tumour suppressor activity.

PMID- 19098712
TI  - Rng3, a member of the UCS family of myosin co-chaperones, associates with myosin
      heavy chains cotranslationally.
AB  - The production of functional myosin heavy chains in many eukaryotic organisms
      requires the function of proteins containing UCS domains (UNC-45/CRO1/She4),
      which bind to the myosin head domain and stimulate its folding. UCS proteins are
      essential for myosin-related functions such as muscle formation, RNA localization
      and cytokinesis. Here, we show that the Schizosaccharomyces pombe UCS protein
      Rng3 associates with polysomes, suggesting that UCS proteins might assist myosin
      folding cotranslationally. To identify Rng3 cotranslational targets
      systematically, we purified Rng3-associated RNAs and used DNA microarrays to
      identify the transcripts. Rng3 copurified with only seven transcripts (around
      0.1% of S. pombe genes), including all five messenger RNAs encoding myosin heavy
      chains. These results suggest that every myosin heavy chain in S. pombe is a
      cotranslational target of Rng3. Furthermore, our data suggest that microarray
      based approaches allow the genome-wide identification of cotranslational
      chaperone targets, and thus pave the way for the dissection of translation-linked
      chaperone networks.

PMID- 19098713
TI  - NF-kappaB p52:RelB heterodimer recognizes two classes of kappaB sites with two
      distinct modes.
AB  - The X-ray structure of the nuclear factor-kappaB (NF-kappaB) p52:RelB:kappaB DNA
      complex reveals a new recognition feature not previously seen in other NF
      kappaB:kappaB DNA complexes. Arg 125 of RelB is in contact with an additional DNA
      base pair. Surprisingly, the p52:RelB R125A mutant heterodimer shows defects both
      in DNA binding and in transcriptional activity only to a subclass of kappaB
      sites. We found that the Arg 125-sensitive kappaB sites contain more contiguous
      and centrally located A:T base pairs than do the insensitive sites. A protein
      induced kink observed in this complex, which used an AT-rich kappaB site, might
      allow the DNA contact by Arg 125; such a kink might not be possible in complexes
      with non-AT-rich kappaB sites. Furthermore, we show that the p52:RelB heterodimer
      binds to a broader spectrum of kappaB sites when compared with the p50:RelA
      heterodimer. We suggest that the p52:RelB heterodimer is more adaptable to
      complement sequence and structural variations in kappaB sites when compared with
      other NF-kappaB dimers.

PMID- 19098838
TI  - ACG Presidential Introduction.

PMID- 19098714
TI  - miR-142-3p restricts cAMP production in CD4+CD25- T cells and CD4+CD25+ TREG
      cells by targeting AC9 mRNA.
AB  - Cyclic AMP (cAMP) is a ubiquitous second messenger that regulates diverse
      cellular functions. It has been found that CD4(+)CD25(+) regulatory T (T(REG))
      cells exert their suppressor function by transferring cAMP to responder T cells.
      Here, we show that miR-142-3p regulates the production of cAMP by targeting
      adenylyl cyclase (AC) 9 messenger RNA in CD4(+)CD25(-) T cells and CD4(+)CD25(+)
      T(REG) cells. miR-142-3p limits the level of cAMP in CD4(+)CD25(-) T cells by
      inhibiting AC9 production, whereas forkhead box P3 (FOXP3) downregulates miR-142
      3p to keep the AC9/cAMP pathway active in CD4(+)CD25(+) T(REG) cells. These
      findings reveal a new molecular mechanism through which CD4(+)CD25(+) T(REG)
      cells contain a high level of cAMP for their suppressor function, and also
      suggest that the microRNA controlling AC expression might restrict the final
      level of cAMP in various types of cells.

PMID- 19098839
TI  - ACG Presidential Address. Major changes: rising to face the challenges and
      opportunities for clinical gastroenterology.

PMID- 19098841
TI  - Commentary: Gastroenterology and hepatology: an evolving marriage, not an
      imminent divorce.

PMID- 19098842
TI  - Response: evolution of training in gastroenterology and hepatology: working
      together is the solution.

PMID- 19098843
TI  - The application of Prague C and M criteria in the diagnosis of Barrett's
      esophagus in an ethnic Chinese population.
AB  - OBJECTIVES: To investigate the prevalence of endoscopically suspected esophageal
      metaplasia (ESEM) in an ethnic Chinese population by endoscopic and pathologic
      evaluation and to assess the utility of Prague C and M criteria. METHODS:
      Consecutive patients who received esophagogastroduodenoscopy either as a part of
      therapy for various upper abdominal symptoms or as an annual health check-up were
      evaluated for the existence of ESEM and Barrett's esophagus (BE). Biopsy with
      standardized random four pieces every 2 cm from the four quarters of esophagus
      with ESEM lesion was performed. BE was defined by histological verification of
      specialized intestinal metaplasia and gastric metaplasia and was categorized
      according to the Prague C and M criteria. RESULTS: A total of 5,179 subjects were
      screened from Jan. 2007 to Dec. 2007. This study enrolled 4,797, including 3,386
      for referral endoscopy and 1,411 for screening endoscopy. Prevalence of BE among
      the referral endoscopy, screening endoscopy, and overall was 1.06%, 0.35%, and
      0.85%, respectively. A total of 41 subjects with BE were detected among 93 ESEM
      subjects. Short segment BE (75.6%, n=31) was more prevalent than long segment BE
      (24.4%, n=10). The proportions of BE from subjects with ESEM by Prague C and M
      criteria were C< or =1M1 38.9% (19/50), C< or =1M2 40% (12/30), and CxM> or =3
      76.9% (10/13). CONCLUSIONS: On the basis of the standardized protocol with random
      four-quadrate endoscopic biopsy, we have demonstrated the utility of Prague C and
      M criteria to characterize the BE in an ethnic Chinese population.

PMID- 19098844
TI  - Cumulative H. pylori eradication rates in clinical practice by adopting first and
      second-line regimens proposed by the Maastricht III consensus and a third-line
      empirical regimen.
AB  - OBJECTIVES: The European Helicobacter Study Group has recently issued the current
      concepts in the management of Helicobacter pylori infection (Maastricht III
      Consensus Report, 2005). The aim of the study was to examine the cumulative H.
      pylori eradication rates that can be achieved in clinical practice by adopting
      first and second regimens as proposed by the Maastricht III consensus and a third
      line empirical levofloxacin-based regimen. METHODS: H. pylori-positive patients
      were treated initially with a first-line eradication triple regimen consisting of
      omeprazole, amoxicillin, and clarithromycin and subsequently with a second-line
      quadruple regimen consisting of omeprazole, bismuth, metronidazole, and
      tetracycline. Finally, after two previous H. pylori eradication failures,
      patients received omeprazole, amoxicillin, and levofloxacin, as a third-line
      empirical strategy. The success rate was calculated by both intention-to-treat
      (ITT) and per protocol (PP) analyses. RESULTS: In total, 540 consecutive H.
      pylori-positive patients received first-line treatment (omeprazole, amoxicillin,
      and clarithromycin). H. pylori were eradicated in 380 patients and 40 patients
      were withdrawn (ITT, 70.3%; PP, 76%). The remaining 120 H. pylori-positive
      patients received second-line treatment (omeprazole, bismuth, metronidazole, and
      tetracycline). H. pylori were eradicated in 83 patients and 7 patients were
      withdrawn (ITT, 69.1%; PP, 73.45%). Finally, the remaining 30 H. pylori-positive
      patients received third-line treatment (omeprazole, amoxicillin, and
      levofloxacin). H. pylori were eradicated in 21 patients and 0 patients were
      withdrawn (ITT, 70%; PP, 70%). Thus, out of 540 patients initially included in
      the study, H. pylori were eradicated in 484 patients, 47 were withdrawn, and only
      9 remained positive. These results give 89.6% ITT and 98.1% PP cumulative H.
      pylori eradication rates. CONCLUSIONS: By adopting first- and second-line
      regimens, as proposed by the Maastricht III consensus and a third-line
      levofloxacin-based empirical regimen, high cumulative H. pylori eradication rates
      can be achieved. Thus, a substantial number of cultures to determine sensitivity
      to antibiotics can be avoided with beneficial consequences concerning cost.

PMID- 19098845
TI  - H. pylori treatment: new wine in old bottles?
AB  - Treatment of Helicobacter pylori infection has become a problem in many clinical
      settings. Eradication rates are at the lowest levels seen in the past decade and
      are likely to fall further as antimicrobial resistance becomes more prevalent
      worldwide. Culture of H. pylori and antimicrobial sensitivity testing is still
      not generally available; therefore treatment strategies that are selected based
      on information that is specific to the individual patient are often not possible.
      Current strategies for treatment in most Western countries consist of initial
      therapy with a combination of a proton pump inhibitor therapy with amoxicillin
      and clarithromycin, with quadruple therapy reserved for failures. Sequential
      therapy is an attractive new alternative for initial treatment and may offer an
      alternative to conventional therapies. The choice of initial therapy is in a
      state of flux and this article will discuss alternative treatment strategies that
      clinicians may use in this difficult environment.

PMID- 19098846
TI  - Risk factors for ERCP-related complications: a prospective multicenter study.
AB  - OBJECTIVES: To investigate the potential risk factors for endoscopic retrograde
      cholangiopancreatography (ERCP) complications and to identify whether the risk
      factors are different for pancreatitis and asymptomatic hyperamylasemia. METHODS:
      Consecutive ERCP procedures were studied at 14 centers in China from May 2006 to
      April 2007. The complications after the patients' first-only procedures were
      evaluated. Multivariate analysis based on the first-only procedures was used to
      identify the risk factors. RESULTS: A total of 3,178 procedures were performed on
      2,691 patients. Overall, complications developed in 213 (7.92%) patients,
      pancreatitis in 116 (4.31%), and asymptomatic hyperamylasemia in 396 (14.72%). In
      the multivariate analysis, female gender (adjusted odds ratios (ORs): 1.52, 95%
      confidence interval (CI): 1.14-2.02, P=0.004), periampullary diverticulum (OR:
      2.02, 95% CI: 1.49-2.73, P<0.001), cannulation time >10 min (OR: 1.51, 95% CI:
      1.08-2.10, P=0.016), > or =1 pancreatic deep wire pass (OR: 1.80, 95% CI: 1.33
      2.42, P<0.001), and needle-knife precut (OR: 2.70, 95% CI: 1.42-5.14, P=0.002)
      were risk factors for overall complications. Female gender (OR: 1.84, 95% CI:
      1.25-2.70, P=0.002), age < or =60 year (OR: 1.59, 95% CI: 1.06-2.39, P=0.025),
      cannulation time>10 min (OR: 1.76, 95% CI: 1.13-2.74, P=0.012), > or =1
      pancreatic deep wire pass (OR: 2.77, 95% CI: 1.79-4.30, P<0.001), and needle
      knife precut (OR: 4.34, 95% CI: 1.92-9.79, P<0.001) were risk factors for
      pancreatitis. Cannulation time>10 min (OR: 1.96, 95% CI: 1.52-2.54, P<0.001), >
      or =1 pancreatic deep wire pass (OR: 2.24, 95% CI: 1.74-2.89, P<0.001), needle
      knife precut (OR: 2.34, 95% CI: 1.32-4.14, P=0.004), and major papilla pancreatic
      sphincterotomy (OR: 1.71, 95% CI: 1.23-2.37, P=0.001) were risk factors for
      asymptomatic hyperamylasemia. CONCLUSIONS: Patient-related factors are as
      important as procedure-related factors in determining high-risk predictors for
      post-ERCP overall complications and pancreatitis. However, the risk factors for
      asymptomatic hyperamylasemia may be mostly procedure related.

PMID- 19098847
TI  - Efficacy of cap-assisted colonoscopy in comparison with regular colonoscopy: a
      randomized controlled trial.
AB  - OBJECTIVES: Colonoscopy cannot be completed in up to 10% of cases. We postulate
      that cap-assisted colonoscopy (CAC), by fitting a mucosectomy cap to the tip of a
      colonoscope, could improve the outcome. METHODS: We conducted a prospective
      randomized controlled trial in two regional endoscopy centers. All colonoscopies
      were performed by experienced colonoscopists. Patients 18 years or older
      undergoing their first colonoscopy were recruited. Patients were randomized to
      the CAC group or to the regular colonoscopy (RC) group. The first successful
      cecal intubation rate, rescue cecal intubation rate, cecal intubation and total
      colonoscopy times, and polyp detection rate were compared. RESULTS: One thousand
      patients were enrolled (mean age 52.6 years, 46% men). There was no statistically
      significant difference in the first successful cecal intubation rate between CAC
      and RC groups (96.2% vs. 94.6%, P=0.23). The cecal intubation and total
      colonoscopy times were shorter in the CAC group than in the RC group (6.0+/-4.0
      min vs. 7.2+/-4.8 min, P<0.001; 14.7+/-8.6 min vs. 16.7+/-10.3 min, P=0.001). The
      adenoma detection rate was significantly lower in the CAC group than in the RC
      group (30.5% vs. 37.5%, P=0.018), but there was no significant difference in the
      detection of advanced lesions. In case of failing cecal intubation, use of CAC as
      a rescue method could achieve a higher success rate than RC (66.7% vs. 21.1%,
      P=0.003). CONCLUSIONS: Among experienced colonoscopists, CAC did not improve the
      initial cecal intubation rate and had a lower adenoma detection rate. However, it
      shortened the cecal intubation time and performed better as a rescue method. Its
      utilization should be reserved for selected cases, especially when initial cecal
      intubation fails.

PMID- 19098848
TI  - How safe and successful are live demonstrations of therapeutic ERCP? A large
      multicenter study.
AB  - OBJECTIVES: Live demonstrations of endoscopic retrograde cholangiopancreatography
      (ERCP) have a high educational value and contribute significantly to endoscopy
      development and training. However, the success and safety of live demonstration
      have been questioned. The aim of this study was to evaluate the success rate and
      complications of therapeutic ERCP among patients who participated in live
      demonstrations. METHODS: Patients who underwent therapeutic ERCP during live
      demonstrations at gastrointestinal endoscopy conferences in China between January
      2002 and December 2007 were included. The matched control for each patient was a
      patient admitted to the same ERCP unit with similar indication, who received ERCP
      by an endoscopist with similar experience as those who performed the live
      demonstration. Patient's age, gender, indication, success rate, and complications
      of ERCP were collected and compared. ERCP outcomes between local and visiting
      faculty were also compared. RESULTS: In total, 36 conferences with live ERCP
      demonstrations involving 406 patients were held in 14 endoscopy centers. There
      were no significant differences in patients' gender, age, and indications between
      live demonstrations and controls. The overall complication rate of ERCP in live
      demonstrations was not significantly different compared with controls (10.3% vs.
      8.6%, P=0.473). However, the success rate was significantly lower in live
      demonstrations than in controls (94.1% vs. 97.5%, P=0.021). The success and
      complication rates of ERCP performed by local faculty, domestic visiting, and
      foreign visiting faculties were similar. CONCLUSIONS: Although the success rate
      of therapeutic ERCP performed during live demonstrations was lower than that of
      routine procedures, the overall complication rate did not significantly increase.
      ERCP performed by visiting endoscopists was as safe as that done by local faculty
      in live demonstrations.

PMID- 19098849
TI  - Cervical esophageal perforations at the time of endoscopic ultrasound: a
      prospective evaluation of frequency, outcomes, and patient management.
AB  - OBJECTIVES: With the exception of one retrospective survey, there are currently
      no prospectively published data about the frequency of cervical esophageal
      perforation at the time of endoscopic ultrasound (CEP-EUS). We prospectively
      investigated the frequency of CEP-EUS and the outcomes and management of patients
      sustaining CEP-EUS. METHODS: All patients that underwent upper EUS by a single
      experienced endosonographer over a 7-year period were enrolled. All indications
      and immediate complications encountered, the baseline demographics, indication of
      the procedures, surgical interventions, length of hospital stay, and the final
      outcomes of the patients were prospectively recorded. RESULTS: A total of 5,225
      EUS procedures were performed. Lower gastrointestinal tract EUS procedures
      (n=331) were excluded from the analysis, and thus 4,894 upper EUSs constitute
      this study. The mean age of the patients was 59.7 years (s.d. 14.3 years); 54%
      patients were men and 79% were white. Indications for EUS included
      pancreaticobiliary (58%), esophageal (14%), mediastinal (14%), gastric (9%),
      celiac blocks (1%), and other (4%). Of 4,894 patients, 3 (0.06%, exact 95%
      confidence interval: 0.01-0.18) suffered CEP-EUS. The curvilinear echoendoscope
      was used in all three patients. All patients were octogenarians and women. All
      perforations were suspected at the time of intubation. Esophagogram confirmed
      contained perforation in all patients. All patients were immediately admitted and
      underwent surgical repair with a neck incision and recovered completely. The
      length of hospital stay was 6, 11, and 23 days respectively. All patients resumed
      swallowing without complications. One patient died from progressive pancreatic
      cancer 6 months after Whipple's procedure. The two other patients remained alive
      and well 12 and 22 months after the procedure. CONCLUSIONS: CEP-EUS is rare but a
      potentially devastating event for the patient and the treating physician.
      Although rare, the incidence is 2- to 3-fold higher than what has been reported
      in the survey literature. Early recognition and treatment is crucial for prompt
      intervention and complete recovery from CEP-EUS. These data can be used by
      endosonographers to counsel their patients about frequency, management, and
      outcomes of CEP-EUS.

PMID- 19098851
TI  - The histologic spectrum of liver disease in African-American, non-Hispanic white,
      and Hispanic obesity surgery patients.
AB  - OBJECTIVES: Non-alcoholic fatty liver disease (NAFLD) is a prominent cause of
      chronic liver disease in African Americans, non-Hispanic whites, and Hispanics.
      The aim of this study was to evaluate ethnic differences in the prevalence of
      NAFLD and non-alcoholic steatohepatitis (NASH) and to compare the severity of
      histologic features of NASH in obesity surgery patients. METHODS: Subjects
      consisted of 238 patients who had a routine liver biopsy at the time of obesity
      surgery. Demographic and clinical variables pertaining to the metabolic syndrome
      were collected retrospectively. Liver biopsies were evaluated according to the
      scoring system proposed by the Nonalcoholic Steatohepatitis Clinical Research
      Network and NASH was defined as a NASH activity score > or =5. RESULTS: African
      Americans had lower rates of steatosis than non-Hispanic whites (P<0.001) and
      Hispanics (P=0.03). Among patients with steatosis, African Americans had lower
      rates of NASH than non-Hispanic whites (P=0.05) and Hispanics (P=0.02) and lower
      rates of fibrosis score > or =F2 than non-Hispanic whites (P=0.002) and Hispanics
      (P=0.04). Ethnic differences in rates of NAFLD, NASH, and fibrosis > or =F2
      persisted when controlling for demographic variables and features of the
      metabolic syndrome in logistic regression analysis. There were no significant
      differences in steatosis, NASH, or fibrosis > or =F2 between non-Hispanic whites
      and Hispanics. CONCLUSIONS: African-American obesity surgery patients have a
      lower rate of NAFLD, NASH, and less severe fibrosis than non-Hispanic whites and
      Hispanics.

PMID- 19098850
TI  - Prevalence and factors related to hepatitis B and C in inflammatory bowel disease
      patients in Spain: a nationwide, multicenter study.
AB  - OBJECTIVES: Limited information suggests the existence of a high prevalence of
      hepatitis B (HBV) and C virus (HCV) infection in inflammatory bowel disease
      (IBD). This knowledge is relevant because the viruses may reactivate under
      immunosuppressive therapy. The objectives of this study are to assess the
      prevalence of HBV and HCV infection in IBD, in a nationwide study, and to
      evaluate associated risk factors. METHODS: This cross-sectional multicenter study
      included 2,076 IBD patients, consecutively recruited in 17 Spanish hospitals.
      Factors related to IBD (severity, invasive procedures, etc.) and to infection
      (transfusions, drug abuse, etc.) were registered. Independent risk factors for
      viral infection were evaluated using logistic regression analysis. RESULTS:
      Present and/or past HBV and HCV infection was found in 9.7% of patients of both
      ulcerative colitis (UC) and Crohn's disease (CD) (UC: HBsAg 0.8%, anti-HBc 8%,
      anti-HCV 1.3%; CD: HBsAg 0.6%, anti-HBc 7.1%, anti-HCV 2.3 %). Effective
      vaccination (anti-HBs, without anti-HBc) was present in 12% of patients. In
      multivariate analysis, age (odds ratio (OR) 1.04; 95% confidence interval (CI)
      1.02-1.06; P=0.000), family history of hepatitis (OR 2.48; 95% CI 1.3-4.74;
      P=0.006) and moderate-to-severe IBD disease (OR 2.5; 95% CI 1.02-6.15; P=0.046)
      were significantly related to HBV, whereas transfusions (OR 2.66; 95% CI 1.2
      5.87; P=0.015) and antibiotic use (OR 2.66; 95% CI 1.1-6.3; P=0.03) were
      significantly related to HCV. The significance for transfusions was lost if they
      were administered after 1991, when HCV markers became mandatory in blood banks.
      CONCLUSIONS: Prevalence of HBV and HCV infection in IBD is similar to that of the
      general population of reference and lower than that in previously published
      series. This fact, in addition to the lack of association with invasive
      procedures, suggests the existence of adequate preventive measures in centers
      attending to these patients. The low percentage of effective vaccination makes it
      mandatory to intensify B virus vaccination in IBD.

PMID- 19098852
TI  - A randomized study of extended treatment with peginterferon alpha-2b plus
      ribavirin based on time to HCV RNA negative-status in patients with genotype 1b
      chronic hepatitis C.
AB  - OBJECTIVES: The treatment of patients with hepatitis C virus (HCV) genotype 1
      with peginterferon plus ribavirin treatment for more than 48 weeks demonstrated
      high sustained virological response (SVR) rates. Although many studies extended
      the duration of therapy from 48 weeks to 72 weeks, the optimal duration has not
      yet been determined. METHODS: A total of 113 genotype 1b patients with high viral
      load were randomized at baseline to the standard (n=56) or extended (n=57)
      treatment group. The standard group patients received 48 weeks of peginterferon
      plus ribavirin treatment. In the extended group, the treatment was performed for
      44 weeks after patients became negative for HCV RNA (total duration 48-68 weeks).
      RESULTS: The SVR rate of the standard and extended group was 36% (20 of 56) and
      53% (30 of 57; P=0.07). However, the extended group patients who became negative
      for HCV RNA between weeks 16 and 24 had a significantly higher SVR rate (78%; 7
      of 9) than that of standard group (9%, 1 of 11; P=0.005). The predictive factors
      for the SVR were the treatment regimen (the standard vs. extended treatment) and
      the time to HCV RNA negative-status. CONCLUSIONS: The extended treatment
      significantly increased the SVR rate in patients who were HCV RNA negative at 16
      24 weeks.

PMID- 19098853
TI  - Insulin resistance in chronic hepatitis B virus infection.
AB  - OBJECTIVES: Chronic hepatitis C virus infection is associated with insulin
      resistance (IR), and both host and viral factors are important in its
      development. The association and the predictors of IR in chronic hepatitis B
      virus (CHBV) infection remain unclear. METHODS: A total of 69 CHBV-infected
      subjects were examined to study the relationship between histological findings
      and anthropometric and biochemical data, including IR determined by the
      homeostasis model assessment (HOMA-IR). To assess the influence of CHBV infection
      on IR independent of any effect of hepatic fibrosis, overweight, or sex we also
      compared fasting serum insulin, C-peptide, HOMA-IR, HOMA-beta (measure of beta
      cell function) and C-peptide-insulin ratio (to distinguish impaired insulin
      degradation (low ratio) from insulin hypersecretion (normal ratio)) levels
      between the subset of 14 male normal weight (body mass index, BMI<23) CHBV
      patients with stage 0 or 1 hepatic fibrosis and 50 male normal weight healthy
      controls matched by age and anthropometry (BMI and waist circumference). RESULTS:
      A total of 31 (44.9%) CHBV-infected patients were overweight (BMI>23 kg/m(2)) and
      18 (26.1%) were obese (BMI>25 kg/m(2)). IR was seen in 34 (49.3%) patients. BMI
      (Spearman's coefficient=-0.436; P<0.001) and serum triglyceride levels
      (Spearman's coefficient=-0.307; P=0.010) were univariate predictors of IR. In
      multiple linear regression analysis, only BMI (P<0.001) was an independent
      predictor of HOMA-IR. The subgroup of CHBV-infected patients and the controls had
      comparable levels of all markers of IR, including fasting glucose, insulin, C
      peptide, and HOMA-IR. CONCLUSIONS: IR in CHBV-infected patients is a reflection
      of the host metabolic profile and CHBV infection is not in itself correlated with
      IR.

PMID- 19098854
TI  - Minocycline in the treatment of patients with primary sclerosing cholangitis:
      results of a pilot study.
AB  - OBJECTIVES: Primary sclerosing cholangitis (PSC) is a chronic cholestatic liver
      disease of young adults that is associated with significant morbidity and
      mortality. No effective medical therapy is available. Minocycline has been found
      to exert biological effects independent of its antimicrobial properties,
      including anti-inflammatory activities such as inhibition of inducible nitric
      oxide synthase, upregulation of interleukin 10, and direct suppressive effect on
      B- and T-cell function. Minocycline may also inhibit cell death pathways by
      reducing both proapoptotic and proinflammatory enzyme activation. We sought to
      investigate the safety and efficacy of minocycline among patients with PSC.
      METHODS: We evaluated the efficacy of minocycline in patients with PSC in a pilot
      study. Sixteen patients with PSC were enrolled. Minocycline, 100 mg orally twice
      daily, was given for 1 year. RESULTS: A statistically significant improvement in
      serum alkaline phosphatase activity (330 U/l vs. 265 U/l, P=0.04) and Mayo risk
      score (0.55 vs. 0.02, P=0.05) occurred with treatment. Serum bilirubin and
      albumin remained essentially unchanged while on treatment. CONCLUSIONS: The
      results of this pilot study indicate that minocycline is reasonably well
      tolerated and potentially effective in patients with PSC. These findings might be
      explained by the anti-inflammatory and antiapoptotic properties of minocycline.
      Though the data presented are too preliminary to support the clinical use of
      minocycline in the treatment of PSC at this time, its use should be further
      investigated.

PMID- 19098855
TI  - Known risk factors do not explain disparities in gallstone prevalence between
      Denmark and northeast Germany.
AB  - OBJECTIVES: Gallstones are a common disease worldwide, with disparities in the
      prevalence of the disease in different settings. The aim of the present study was
      to assess if different distributions of risk factors could explain the
      disparities in the prevalence of gallstone disease between Denmark and northeast
      Germany. METHODS: Data of 5,559 subjects from the Danish MONICA survey and of
      3,647 subjects of the German Study of Health in Pomerania were investigated.
      Gallstone disease was defined as a prior history of cholecystectomy or the
      presence of sonographically diagnosed gallstones. Logistic regression models were
      performed to assess the confounding effect of selected risk factors on regional
      disparities in gallstone disease. RESULTS: After adjustment for age and
      vocational training, German subjects (women: Odds ratio, OR, 2.46 (95% confidence
      interval, CI: 2.07-2.91); men: OR, 1.89 (95% CI: 1.52-2.36)) had approximatively
      twice the odds of gallstones than Danes. Inclusion of lifestyle factors (smoking,
      alcohol intake, coffee use) did not affect this result, whereas adjustment for
      body mass index (BMI), lipids, diabetes, and use of oral contraceptives,
      menopausal hormone therapy (MHT) and parity (women only) changed the estimates
      considerable, but still Germans (women: OR, 1.65 (95% CI: 1.36-2.00); men: OR,
      1.61 (95% CI: 1.27-2.04)) had higher odds than Danes. CONCLUSIONS: German
      individuals had a higher prevalence of gallstones than Danes. This difference was
      partly explained by a higher BMI, unfavorable lipid levels, higher prevalence of
      diabetes, and a more frequent use of OR and MHT in German subjects. Further
      research is needed to evaluate the impact of unmeasured predictors, including
      genetic components, on the population-related risk of gallstones.

PMID- 19098856
TI  - Risk of venous thromboembolism in patients with liver disease: a nationwide
      population-based case-control study.
AB  - OBJECTIVES: It is known that liver disease can cause an imbalance in the
      coagulation system, but available data on liver disease and risk of venous
      thromboembolism are conflicting. We examined the risk of venous thromboembolism
      in patients hospitalized with liver diseases. METHODS: We conducted a nationwide
      Danish case-control study of incident cases of venous thromboembolism from 1980
      to 2005 using population-based data from the National Registry of Patients, and
      from the Civil Registration System. We used conditional logistic regression to
      compute the relative risk of venous thromboembolism in patients with liver
      disease compared to population controls. We then excluded patients with known
      malignancy (diagnosed either before or up to 3 months after the venous
      thromboembolism) or fractures, trauma, surgery, or pregnancy within 90 days
      before the venous thromboembolism to estimate the risk associated with unprovoked
      venous thromboembolism. RESULTS: A total of 99,444 patients with venous
      thromboembolism and 496,872 population controls were included in the study.
      Patients with liver disease had a clearly increased relative risk of venous
      thromboembolism, varying from 1.74 (95% CI, 1.54-1.95) for liver cirrhosis to
      1.87 (95% CI, 1.73-2.03) for non-cirrhotic liver disease. The risks were higher
      for deep venous thrombosis compared with pulmonary embolism. In the analysis,
      restricted to 67,519 patients with unprovoked venous thromboembolism and 308,614
      population controls, we found slightly higher relative risks: 2.06 (95% CI, 1.79
      2.38) for liver cirrhosis and 2.10 (95% CI, 1.91-2.31) for non-cirrhotic liver
      disease. CONCLUSIONS: Patients with liver disease have a substantially increased
      risk of venous thromboembolism.

PMID- 19098857
TI  - Expression of the high-affinity IgG receptor FcRI (CD64) in patients with
      inflammatory bowel disease: a new biomarker for gastroenterologic diagnostics.
AB  - OBJECTIVES: We sought to determine the quantitative expression of the high
      affinity Fc receptor (CD64) on polymorphonuclear neutrophils (PMNs) in
      inflammatory and functional conditions of the intestine and investigated its
      correlation with clinical and biological parameters of inflammation. METHODS: The
      quantitative expression of CD64 was determined by fluorescence-activated cell
      sorting analysis in patients with active or inactive inflammatory bowel disease
      (IBD, n=76), infectious enterocolitis, lactose and/or fructose intolerance, and
      healthy subjects. RESULTS: The quantitative expression of CD64 in patients with
      active IBD (3,398+/-3,589 molecules per PMN, n=27) was significantly higher than
      in healthy subjects (607+/-265, n=28, P<0.001) or in patients with
      lactose/fructose intolerance (531+/-150, n=32, P<0.001). The expression of CD64
      correlated significantly with C-reactive protein (CRP, 0.65, P<0.0001), Crohn's
      disease activity index (CDAI, 0.53, P<0.0001), and colitis activity index (CAI,
      0.63, P<0.0001) in patients with IBD. With a cutoff point of 800, CD64 had a
      sensitivity of 88% and a specificity of 93% in discriminating between
      lactose/fructose intolerance and active IBD. The quantitative expression of CD64
      in patients with infectious enterocolitis (19,190+/-8,920, n=22) was
      significantly higher than in patients with active IBD (P<0.001). With a cutoff
      point of 10,000, CD64 showed a sensitivity of 96% and a specificity of 97% in
      discriminating between infectious enterocolitis and active IBD. CONCLUSIONS: CD64
      could serve as a valuable tool to discriminate between IBD, infectious
      enterocolitis, and functional intestinal disorders.

PMID- 19098858
TI  - Polymorphism of the IRGM gene might predispose to fistulizing behavior in Crohn's
      disease.
AB  - OBJECTIVES: Recently, genome-wide association analyses have identified single
      nucleotide polymorphisms in the IRGM gene (rs1000113 and rs4958847) as strong
      candidate susceptibility factors for Crohn's disease (CD). The aim of our study
      was to test whether these variants are associated with inflammatory bowel disease
      (IBD) in adult- and childhood-onset Italian patients. METHODS: Allele and
      genotype frequencies of rs1000113 and rs4958847 were determined in 823 CD (265
      younger than 19 years at diagnosis), 353 ulcerative colitis (UC) (130 younger
      than 19 years at diagnosis), and 578 controls. Genotype distributions were
      examined both within IBD clinical sub-phenotypes and CARD15 genotypes. RESULTS:
      rs1000113 and rs4958847 were both associated with adult-onset (P=2 x 10(-4);
      P=2.5 x 10(-3), respectively) and childhood-onset (P=4 x 10(-4); P=8 x 10(-3),
      respectively) CD cohorts. Similarly, the genotype frequencies remained
      significantly different for both variants (adult rs1000113, P=1 x 10(-4);
      rs4958847, P=1 x 10(-3); pediatric rs1000113, P=2.3 x 10(-4); rs4958847, P=9.6 x
      10(-3)). At logistic regression, the rs4958847 polymorphism was associated with
      fistulizing behavior (P=0.037, OR=1.54, CI=1.02-2.31) and perianal fistulas
      (P=0.045, OR=1.55, CI=1.01-2.38). Conversely, no association with UC and sub
      phenotypes was shown. CONCLUSIONS: We replicated the previously reported
      associations between CD and rs1000113 and rs4958847, confirming that IRGM is a
      susceptibility locus only for CD, either adult- or early-onset in the Italian
      population; furthermore, we have also shown its influence on specific clinical
      features (fistulizing disease).

PMID- 19098859
TI  - Inflammatory bowel disease in CGD reproduces the clinicopathological features of
      Crohn's disease.
AB  - OBJECTIVES: Patients with chronic granulomatous disease (CGD), a rare congenital
      disorder characterized by defective neutrophil function, frequently develop an
      inflammatory bowel disease similar to Crohn's disease. The clinical presentations
      and concordance between the features of the bowel disease in these two conditions
      have never been formally evaluated. METHODS: Retrospective case note analysis of
      all adult patients with CGD treated at a tertiary care hospital. RESULTS: A total
      of 25 eligible patients were identified. Of these, 14 (56%) had experienced
      gastrointestinal symptoms in the preceding 3 years; and 11 (44%) had documented
      gastrointestinal inflammation not secondary to infection, manifesting throughout
      the alimentary canal including the upper gastrointestinal tract (45%), small
      intestine (27%), colon (73%), and rectum (73%). All had discontinuous
      inflammation and perianal involvement, and approximately half (55%) demonstrated
      epithelioid granulomata on histology. All patients fulfilled the Lennard-Jones
      criteria for the diagnosis of Crohn's disease. Therapeutic responses were
      observed in five patients to 5-aminosalicylates, and in individual patients to
      thalidomide, interferon-gamma, azathioprine, infliximab, and intestinal
      resection. CONCLUSIONS: There are striking clinical and pathological resemblances
      between the bowel diseases observed in CGD and Crohn's disease, supporting the
      possibility of mechanistic similarities in their pathogenesis. Patients with CGD
      appear particularly prone to developing perianal disease.

PMID- 19098860
TI  - Pilot study on the effect of linaclotide in patients with chronic constipation.
AB  - OBJECTIVES: Chronic constipation is a common gastrointestinal disorder with
      limited treatment options. Oral administration of linaclotide, a novel peptide
      agonist of guanylate cyclase-C receptors, has been shown in animal studies to
      stimulate intestinal fluid secretion and transit. In Phase 1 studies in healthy
      human volunteers, linaclotide was well-tolerated, increased bowel movement
      frequency, and loosened stool consistency. METHODS: This randomized, double
      blind, placebo-controlled pilot study evaluated the safety, tolerability, and
      exploratory efficacy of oral linaclotide in 42 patients with chronic
      constipation. Patients were randomized to linaclotide (100, 300, or 1,000 microg)
      or placebo once daily for 2 weeks. Bowel habits (stool frequency, consistency,
      straining, completeness of evacuation) and degree of abdominal discomfort were
      monitored daily using an interactive voice response system. Patient-reported
      outcomes of severity of constipation and overall relief were evaluated weekly.
      RESULTS: Linaclotide treatment produced dose-dependent increases from the
      pretreatment baseline values in weekly complete spontaneous bowel movement
      frequency (range: 2.2-3.2), stool consistency scores (range: 1.1-2.6, 7-point
      scale), and straining scores (range: 0.4-1.5, 7-point scale); corresponding
      placebo increases were 1.3, 0.4, 0.4, respectively. Clinical improvements were
      also demonstrated in abdominal discomfort, severity of constipation, and overall
      relief. Compared to placebo, linaclotide 100 microg/day significantly increased
      spontaneous bowel movement frequency, and linaclotide 1,000 microg/day
      significantly improved stool consistency (P<0.05). Adverse events were primarily
      gastrointestinal, with diarrhea being the most common. CONCLUSIONS: In this pilot
      study, linaclotide treatment improved bowel habits and symptoms of patients with
      chronic constipation. Further randomized controlled trials are warranted.

PMID- 19098861
TI  - Neorectal irritability after short-term preoperative radiotherapy and surgical
      resection for rectal cancer.
AB  - OBJECTIVES: Preoperative radiotherapy followed by rectal resection with total
      mesorectal excision (TME) and colo-anal anastomosis severely compromises
      anorectal function, which has been attributed to a decrease in neorectal capacity
      and neorectal compliance. However, to what extent altered motility of the
      neorectum is involved, is still unknown. The aim of the study was to compare the
      motor response to (prolonged) filling of the (neo-)rectum in patients after
      preoperative radiotherapy and rectal resection with that in healthy volunteers
      (HV). METHODS: Neorectal function (J-pouch or side-to-end anastomosis) was
      studied in 15 patients (median age 61 years, 10 males) 5 months after short-term
      preoperative radiotherapy (5 x 5 Gy) and rectal resection with TME for rectal
      cancer and compared with that of 10 volunteers (median age 41 years, 7 males).
      Furthermore, patients with a colonic J-pouch anastomosis (n=6) were compared with
      patients with a side-to-end anastomosis (n=9). (Neo-)rectal sensitivity was
      assessed using a stepwise isovolumetric and isobaric distension protocol. (Neo
      )rectal motility was determined during prolonged distension at the threshold of
      the urge to defecate. RESULTS: The neorectal volume of patients at the threshold
      of the urge to defecate (125 +/-45 ml) was significantly lower when compared with
      that of HV (272+/-87 ml, P<0.05). The pressure threshold, however, did not differ
      between patients (26+/-9 mm Hg) and HV (21+/-5 mm Hg) and neither did the
      pressure threshold differ between patients with a J-pouch and those with side-to
      end anastomosis. In HV, no rectal contractions were observed during prolonged
      rectal distension. In contrast, in all 15 patients, prolonged isovolumetric and
      isobaric distension induced 3 (range 0-5) rectal contractions/10 min, which were
      associated with an increase in sensation in half of the patients. CONCLUSIONS:
      Patients who underwent preoperative radiotherapy and rectal resection with TME,
      but not HV, developed contractions of the neo-rectum in response to prolonged
      distension. We suggest that this neorectal "irritability" represents a new
      pathophysiological mechanism contributing to the urgency for defecation after
      this multimodality treatment.

PMID- 19098863
TI  - Estimation of impact of American College of Radiology recommendations on CT
      colonography reporting for resection of high-risk adenoma findings.
AB  - OBJECTIVES: The American College of Radiology (ACR) recommends that polyps < or
      =5 mm in size not be reported on computed tomography (CT) colonography studies.
      Patients with 1 or 2 polyps 6-9 mm in size can be offered "CTC surveillance" in 3
      years in lieu of polypectomy. The aim of the study was to determine the impact of
      ACR recommendations on resection of high-risk adenoma findings using an
      endoscopic polyp/histology database. METHODS: Excluding patients with
      inflammatory bowel disease (IBD) and polyposis, 10,034 patients underwent
      colonoscopy and 10,780 polyps were removed from 5,079 patients over a 5-year
      interval. High-risk adenoma findings were defined as an advanced adenoma (> or =1
      cm in size, high-grade dysplasia (HGD), or villous elements) or 3 or more
      adenomas of any size, per postpolypectomy surveillance recommendations. RESULTS:
      A total of 5,079 patients (51%) had at least 1 polyp, 2,907 (29%) had at least 1
      adenoma, and 1,001 (10%) had high-risk adenoma findings, of these, 293 (29%) had
      either 3 adenomas < or =5 mm in size (n=267) or an advanced adenoma < or =5 mm in
      size (or both) and no polyp of any histology > or =6 mm in size. There were 774
      patients with 1 or 2 polyps 6-9 mm in size and no polyps of any histology > or
      =10 mm in size. Of these patients 184 (18% of the patients with high-risk
      adenomas) had either 3 or more adenomas < or =9 mm in size (n=149) or an advanced
      adenoma < or =9 mm in size (or both findings). There were 2,174 patients age > or
      =50 years with the primary indication of screening of whom 326 (15%) had high
      risk adenoma findings. Of these, 108 (33%) had either > or =3 adenomas < or =5 mm
      in size or an advanced adenoma < or =5 mm in size and no polyps > or =6 mm in
      size. An additional 75 (23%) had no polyp > or =10 mm in size, 1 or 2 polyps 6-9
      mm in size and > or =3 adenomas < or =9 mm in size or an advanced adenoma < or =9
      mm in size. CONCLUSIONS: If computed tomographic colonography (CTC) rather than
      colonoscopy were used in this population, assuming 100% sensitivity of CTC for
      polyps > or =6 mm and ACR interpretation recommendations, then 29% of all
      patients and 33% of screening patients age > or =50 years with high-risk adenoma
      findings would be interpreted as normal, and an additional 18-23% of these groups
      with high-risk adenoma findings, respectively, could have polypectomy delayed at
      least 3 years.

PMID- 19098862
TI  - Lymphocytic duodenosis and the spectrum of celiac disease.
AB  - OBJECTIVES: Celiac disease (CD) is a chronic inflammatory disease of the small
      bowel that is characterized by increased intraepithelial lymphocytes (IELs) and
      villous atrophy of the mucosa. It is unclear how often intraepithelial
      lymphocytosis in the absence of atrophy is a manifestation of gluten sensitive
      enteropathy. The objective of this study was to identify factors that
      discriminate patients with CD from those with lymphocytic duodenosis (LD,
      intraepithelial lymphocytosis without villous atrophy). We compared Class 2 HLA
      type, presenting symptoms, and serology in patients with LD and CD. METHODS:
      Retrospective review of 124 systematically assessed patients with LD compared
      with 454 CD patients with villous atrophy. All patients had duodenal biopsies and
      Class 2 HLA typing performed. HLA type, symptoms, serology pattern, and response
      to a gluten-free diet were analyzed using univariate logistic regression
      modeling, adjusted for age and gender. RESULTS: Half of the (63 (51%)) LD
      patients lack the Class 2 HLA genotypes encoding DQ2 or DQ8 whereas only 11 (2%)
      CD patients had neither DQ2 nor DQ8, P<0.001. The genes encoding DQ2 were much
      more prevalent in CD (91%) than that in LD (37%, P<0.001), however, the rate of
      carriage of DQ8 did not differ between the two groups (15% vs. 15%, P=0.9).
      Although diarrhea and weight loss were equally frequent in LD and CD patients, LD
      patients were less likely to be associated with anemia (P=0.007), malaise
      (P=0.006), skin disorder (P=0.007), or a family history of CD (P<0.001). The LD
      subjects were much less likely to have tissue transglutaminase or endomysial
      antibodies than were CD subjects (12% or 0% vs. 87% and 87%; P<0.001,
      respectively). CONCLUSIONS: The LD cohort differs significantly in terms of HLA
      type, serology, and clinical features, suggesting that the majority of patients
      with LD do not belong in the spectrum of CD.

PMID- 19098865
TI  - Elevated serum creatinine as a marker of pancreatic necrosis in acute
      pancreatitis.
AB  - OBJECTIVES: Pancreatic necrosis is a serious complication of acute pancreatitis.
      The identification of simple laboratory tests to detect subjects at risk of
      pancreatic necrosis may direct management and improve outcome. This study focuses
      on the association between routine laboratory tests and the development of
      pancreatic necrosis in patients with acute pancreatitis. METHODS: In a cohort of
      185 patients with acute pancreatitis prospectively enrolled in the Severity of
      Acute Pancreatitis Study, patients with contrast-enhanced computerized tomography
      performed were selected (n=129). Serum hematocrit, creatinine, and urea nitrogen
      on admission and peak values within 48 h of admission were analyzed. The volume
      of intravenous fluid resuscitation was calculated for each patient. RESULTS: Of
      129 patients, 35 (27%) had evidence of pancreatic necrosis. Receiver operating
      characteristic curves for pancreatic necrosis revealed an area under the curve of
      0.79 for admission hematocrit, 0.77 for peak creatinine, and 0.72 for peak urea
      nitrogen. Binary logistic regression yielded that all three tests were
      significantly associated with pancreatic necrosis (P<0.0001), with the highest
      odds ratio, 34.5, for peak creatinine. The volume of intravenous fluid
      resuscitation was similar in patients with and without necrosis. Low admission
      hematocrit (< or =44.8%) yielded a negative predictive value of 89%; elevated
      peak creatinine (>1.8 mg/dl) within 48 h yielded a positive predictive value of
      93%. CONCLUSIONS: We confirm that a low admission hematocrit indicates a low risk
      of pancreatic necrosis (PNec) in patients with acute pancreatitis. In contrast,
      an increase in creatinine within the first 48 h is strongly associated with the
      development of PNec. This finding may have important clinical implications and
      warrants further investigation.

PMID- 19098864
TI  - A report on the International Transglutaminase Autoantibody Workshop for Celiac
      Disease.
AB  - OBJECTIVES: Measurement of transglutaminase autoantibodies (TGAA) is considered
      to be the most efficient single serologic test for celiac disease (CD) by the
      American Gastroenterological Association Institute. We hypothesized that a large
      international collaborative effort toward improving and standardizing TGAA
      measurement is both feasible and necessary. The primary aim of this workshop is
      to compare TGAA assays among various research and clinical laboratories to
      examine assay concordance and improve (and eventually standardize) the TGAA
      assay. METHODS: A total of 20 laboratories (5 commercial laboratories, 15
      research and clinical laboratories) participated that included enzyme-linked
      immunosorbent assay (ELISA) and radiobinding assays. A total of 150 serum samples
      were distributed to each laboratory, with each laboratory receiving an equal
      aliquot that was coded and blinded, composed of 100 healthy control sera and 50
      CD sera. RESULTS: Laboratory sensitivity ranged from 69% to 93% and specificity
      ranged from 96% to 100%. By receiver operator characteristic analysis, the area
      under the curve (C index) ranged from 0.9488 to 0.9904. When analyzing for linear
      correlation, r-squared was as high as 0.8882 but as low as 0.4244 for the celiac
      samples between different laboratories performing ELISA. CONCLUSIONS: This
      transglutaminase autoantibody workshop allows for larger-scale international
      participation for the purposes of improving and eventually standardizing the TGAA
      assay with subsequent workshops.

PMID- 19098867
TI  - Acquisition of Helicobacter pylori infection in early childhood: independent
      contributions of infected mothers, fathers, and siblings.
AB  - OBJECTIVES: Infected siblings, mothers, and fathers have all been suggested to be
      major sources for Helicobacter pylori acquisition among children, but few studies
      have addressed the potential role of various family members simultaneously.
      METHODS: A systematic review was performed on studies investigating intrafamilial
      transmission of childhood H. pylori infection. Within the Ulm Birth Cohort Study,
      which consists of 1,066 healthy newborns, born between November 2000 and November
      2001 and followed up to age 4, and their siblings and parents, the independent
      role of the infection status of parents and siblings in transmission of H. pylori
      among children at age 4 was assessed. RESULTS: Among four studies reporting
      infected mothers and siblings as independent risk factors for childhood H. pylori
      infection, odds ratios (ORs) for childhood infection given an infected sibling
      decreased meaningfully after adjustment for maternal infection status. Within the
      Ulm Birth Cohort Study, the prevalence of infection was 3.0% among index children
      at age 4. In bivariate analyses, maternal, paternal, and sibling infection were
      all strongly and significantly related to infection of the child. However, after
      multivariate adjustment, only maternal infection persisted as the single strong
      and significant risk factor (OR 13.0, 95% confidence interval 3.0-55.2).
      CONCLUSIONS: These patterns suggest that mutual control for H. pylori status of
      other family members is crucial for estimating the role of mothers, fathers, and
      siblings in the transmission of childhood H. pylori infection. In populations
      with low H. pylori prevalence the infected mother is likely to be the main source
      for childhood H. pylori infection.

PMID- 19098866
TI  - Expression pattern and functional relevance of epidermal growth factor receptor
      and cyclooxygenase-2: novel chemotherapeutic targets in pancreatic endocrine
      tumors?
AB  - OBJECTIVES: Pancreatic endocrine tumors represent morphologically and
      biologically heterogeneous neoplasms. Well-differentiated endocrine tumors
      (benign or of uncertain behavior) can be distinguished from well-differentiated
      and poorly differentiated endocrine carcinomas. Although many well-differentiated
      endocrine carcinomas show rather low rates of tumor growth, more than two-thirds
      of pancreatic endocrine carcinomas display distant metastases at the time of
      diagnosis. As the currently applied therapies beyond surgery only achieve partial
      or complete response rates of approximately 15%, additional chemotherapeutic
      targets are needed, especially in the therapy of inoperable and progressive
      pancreatic endocrine carcinomas. METHODS: The expression of epidermal growth
      factor receptor (EGFR) and cyclooxygenase (COX)-2 were investigated in 110
      clinically and pathomorphologically well-characterized pancreatic endocrine
      tumors, using immunohistochemistry and immunoblot analyses. Functional tests were
      performed using the human pancreas carcinoid cell line BON and the mouse
      insulinoma cell line beta-TC-3. RESULTS: The expression of EGFR correlated
      significantly with the grade of malignancy, increasing from low rates of
      expression in benign tumors and tumors of uncertain behavior to high rates of
      expression in well- and poorly differentiated endocrine carcinomas. The
      expression of COX-2 was independent of the malignant potential, but was more
      frequently expressed in primary tumors than in metastases. The treatment of the
      human pancreas carcinoid cell line BON and the mouse insulinoma cell line beta-TC
      3 with EGFR and COX-2 inhibitors (monotherapy and combined therapy) resulted in a
      significant, dose-dependent reduction of cell viability coupled with increased
      apoptosis. CONCLUSIONS: Our results suggest that EGFR and COX-2 may represent
      useful additional chemotherapeutic targets in pancreatic endocrine tumors.

PMID- 19098868
TI  - How I manage H. pylori-negative, NSAID/aspirin-negative peptic ulcers.
AB  - The first and most important action on encountering a patient with unexplained
      gastric or duodenal ulceration is to double check that they are truly H. pylori
      negative and also not taking any ulcerogenic medicines. Once the patient is
      confirmed to be H. pylori negative and NSAID negative, ensure that biopsies of
      the ulcer-whether gastric or duodenal-and of the surrounding gastric and duodenal
      mucosa are obtained to exclude underlying malignancy/lymphoma, Crohn's disease,
      and unusual infectious agents. If the etiology of the ulceration remains
      unexplained, an underlying gastrinoma should be considered and excluded. Patients
      with idiopathic ulcers should be maintained on proton pump inhibitor therapy, and
      higher doses may be required to control acid secretion and prevent ulcer relapse
      in these H. pylori-uninfected subjects.

PMID- 19098870
TI  - HLA and autoimmune digestive disease: a clinically oriented review for
      gastroenterologists.
AB  - OBJECTIVES: The human leukocyte antigen (HLA) system includes genes involved in
      graft-vs-host rejection and in immune response. The discovery that HLAs are
      associated with several diseases led to appealing developments both in basic
      biomedical research and in clinical medicine, and offered the opportunity to
      improve the understanding of pathogenesis and classification of diseases, as well
      as to provide diagnostic and prognostic indicators. The aim of this article is to
      review the association between HLA alleles and autoimmune digestive disease and
      its current relationship with modern HLA nomenclature and clinical practice.
      METHODS: Articles dealing with the association between HLAs and autoimmune
      digestive disease (including celiac disease, inflammatory bowel disease,
      autoimmune hepatitis, sclerosing cholangitis and primary biliary cirrhosis) were
      searched for using Pubmed and SCOPUS databases from earliest records to January
      2008. RESULTS: The review has provided two sections. In the first, we explain the
      basic principles of HLA structure, function, and nomenclature, as an introduction
      to the second section, which describes current associations between HLA alleles
      and digestive diseases. The clinical implications of each HLA association are
      critically discussed. Actually, a clinical role for HLA typing is suggested for
      only a few conditions, e.g., celiac disease. CONCLUSIONS: The knowledge of
      current HLA nomenclature and of its association with some digestive diseases such
      as celiac disease can be useful in clinical practice for diagnostic and
      prognostic purposes. This can avoid improper HLA typing as well as stressing the
      need for further studies on other possible clinical applications.

PMID- 19098872
TI  - Does purgative preparation influence the diagnostic yield of small bowel video
      capsule endoscopy?: A meta-analysis.
AB  - OBJECTIVES: Video capsule endoscopy (VCE) is a useful tool in investigating small
      bowel pathology. However, the role of bowel preparation is controversial.
      Therefore, the aim of this study was to explore the role of bowel preparation and
      in particular its consequences on diagnostic yield in a meta-analysis of all
      relevant studies. METHODS: Extensive English-language medical literature searches
      were performed up to February 2008, using suitable keywords, looking for human
      studies that compared different modes of small bowel preparation (purgative vs.
      clear liquids diet). We examined the effects of this preparation on the following
      three primary end points, diagnostic yield (DY), small bowel visualization
      quality (SBVQ), and VCE completion rate (CR) by meta-analysis of relevant
      studies. RESULTS: A total of 12 eligible studies (6 prospective, 6 retrospective)
      were identified, including 16 sets of data relevant to our primary end points.
      There were significant differences between patients prepared with purgative vs.
      those prepared with clear liquids diet in DY (263 vs. 213 patients, respectively;
      OR (95% CI)=1.813 (1.251-2.628), P=0.002) and SBVQ (404 vs. 249 patients,
      respectively; OR (95% CI)=2.113 (1.252-3.566), P=0.005). There was no
      statistically significant difference regarding CR rate. Purgatives did not affect
      VCE gastric transit time (GTT) or VCE small bowel transit time (SBTT).
      CONCLUSIONS: Pooled data showed that in comparison to clear liquids diet,
      purgative bowel cleansing, before VCE, improves the SBVQ and increases the DY of
      the examination, but does not affect the VCE completion rate.

PMID- 19098873
TI  - Placental transport of immunoglobulins: a clinical review for gastroenterologists
      who prescribe therapeutic monoclonal antibodies to women during conception and
      pregnancy.
AB  - The introduction of biologic therapy with therapeutic monoclonal antibodies to
      the treatment strategies of inflammatory bowel disease (IBD) has significantly
      changed the way clinicians practice. Antibodies are cleared differently than
      small molecules, and knowledge about the pharmacology and immunology of
      immunoglobulins is helpful when using these agents in women preconception and
      during pregnancy. The most commonly used antibody therapies in patients with IBD
      are IgG1 molecules, but others are under development. When treating patients who
      are pregnant or contemplating pregnancy, it is important to remember that
      immunoglobulin G (IgG) is the predominant means of fetal immunity and that it is
      transported across the placenta. This transport happens in a linear fashion as
      the pregnancy progresses, with the largest amount transferred in the third
      trimester. Preferential transport occurs for IgG1, followed by IgG4, and IgG3,
      with IgG2 being the least detected. Understanding the mechanism for
      immunoglobulin transfer will help to understand how to minimize risk of exposure
      of the fetus to the therapeutic monoclonal antibody both in utero and after
      delivery.

PMID- 19098875
TI  - Interventions for treating microscopic colitis: a Cochrane Inflammatory Bowel
      Disease and Functional Bowel Disorders Review Group systematic review of
      randomized trials.
AB  - OBJECTIVES: To conduct a systematic review to determine effective treatments for
      patients with collagenous colitis or lymphocytic colitis, the two subtypes of
      microscopic colitis. METHODS: Relevant papers were identified via the MEDLINE,
      PUBMED, and Cochrane Collaboration databases, manual searches of the references
      of identified papers and review papers on microscopic colitis, as well as
      searches of abstracts from major gastroenterological meetings. RESULTS: All
      studies assessing treatment of microscopic colitis had relatively small sample
      sizes. A total of 10 randomized trials included patients with collagenous
      colitis. Budesonide was studied for induction of response in three trials and for
      maintenance of response in two trials. The pooled odds ratio for inducing
      clinical response with budesonide was 12.32 (95% confidence interval, CI 5.53
      27.46), and for maintaining clinical response was 8.82 (95% CI 3.19-24.37), with
      a number needed to treat (NNT) of 2 patients for each outcome. Budesonide also
      induced and maintained histological response and was well tolerated. Bismuth
      subsalicylate, prednisolone, and mesalamine with or without cholestyramine may be
      effective, whereas Boswellia serrata extract and probiotics were ineffective for
      treating collagenous colitis. Three randomized trials included patients with
      lymphocytic colitis. Budesonide was shown in one study to be effective for
      inducing clinical response (OR 9.00; 95% CI 1.98-40.93), with an NNT of three
      patients. Budesonide also induced histological response and was well tolerated.
      Bismuth subsalicylate and mesalamine with or without cholestyramine may be
      effective for treating lymphocytic colitis. No trials assessed maintenance of
      response in patients with lymphocytic colitis. CONCLUSIONS: Budesonide is
      effective and well tolerated for inducing and maintaining clinical and
      histological responses in patients with collagenous colitis, and for inducing
      clinical and histological responses in patients with lymphocytic colitis.
      Determining the magnitude of benefit is limited by the small sample sizes of the
      studies. The evidence for other agents, including bismuth subsalicylate,
      prednisolone, B. serrata extract, probiotics, and mesalamine with or without
      cholestyramine is weaker. It is not clear that any of these agents induce or
      maintain actual remission of collagenous or lymphocytic colitis, as opposed to
      clinical or histological response.

PMID- 19098877
TI  - Adiponectin and its role in gastrointestinal carcinogenesis.

PMID- 19098878
TI  - Adiponectin and Barrett's esophagus.

PMID- 19098880
TI  - Prolonged cholestasis associated with benazepril therapy.

PMID- 19098881
TI  - Taking a closer look at the rectal examination: beyond the basics.

PMID- 19098883
TI  - Perforated duodenal diverticulitis caused by retained common bile duct stone in
      the diverticulum.

PMID- 19098884
TI  - Waist circumference and cecal intubation time.

PMID- 19098885
TI  - Colonoscopy-induced ischemic colitis in a young patient with no risk factor.

PMID- 19098886
TI  - Trend in Japanese malpractice litigation involving gastrointestinal endoscopy.

PMID- 19098887
TI  - Hemophagocytic syndrome in the course of Crohn's disease: possible association
      with cytomegalovirus infection.

PMID- 19098888
TI  - Acute upper gastrointestinal bleeding associated with Epstein-Barr virus
      reactivation in an immunocompetent patient.

PMID- 19098889
TI  - Sildenafil-induced severe cholestatic hepatotoxicity.

PMID- 19098890
TI  - A case of rectal MALT lymphoma treated by endoscopic resection.

PMID- 19098891
TI  - Deep venous thrombosis related to protein S deficiency revealing celiac disease.

PMID- 19098892
TI  - Acute hepatitis in a patient with cirrhosis and hepatocellular carcinoma treated
      with sorafenib.

PMID- 19098893
TI  - A stress-responsive RNA switch regulates VEGFA expression.
AB  - Ligand binding to structural elements in the non-coding regions of messenger RNA
      modulates gene expression. Ligands such as free metabolites or other small
      molecules directly bind and induce conformational changes in regulatory RNA
      elements known as riboswitches. Other types of RNA switches are activated by
      complexed metabolites-for example, RNA-ligated metabolites such as aminoacyl
      charged transfer RNA in the T-box system, or protein-bound metabolites in the
      glucose- or amino-acid-stimulated terminator-anti-terminator systems. All of
      these switch types are found in bacteria, fungi and plants. Here we report an RNA
      switch in human vascular endothelial growth factor-A (VEGFA, also known as VEGF)
      mRNA 3' untranslated region (UTR) that integrates signals from interferon (IFN)
      gamma and hypoxia to regulate VEGFA translation in myeloid cells. Analogous to
      riboswitches, the VEGFA 3' UTR undergoes a binary conformational change in
      response to environmental signals. However, the VEGFA 3' UTR switch is metabolite
      independent, and the conformational change is dictated by mutually exclusive,
      stimulus-dependent binding of proteins, namely, the IFN-gamma-activated inhibitor
      of translation complex and heterogeneous nuclear ribonucleoprotein L (HNRNPL,
      also known as hnRNP L). We speculate that the VEGFA switch represents the
      founding member of a family of signal-mediated, protein-dependent RNA switches
      that evolved to regulate gene expression in multicellular animals in which the
      precise integration of disparate inputs may be more important than the rapidity
      of response.

PMID- 19098894
TI  - Induced pluripotent stem cells from a spinal muscular atrophy patient.
AB  - Spinal muscular atrophy is one of the most common inherited forms of neurological
      disease leading to infant mortality. Patients have selective loss of lower motor
      neurons resulting in muscle weakness, paralysis and often death. Although patient
      fibroblasts have been used extensively to study spinal muscular atrophy, motor
      neurons have a unique anatomy and physiology which may underlie their
      vulnerability to the disease process. Here we report the generation of induced
      pluripotent stem cells from skin fibroblast samples taken from a child with
      spinal muscular atrophy. These cells expanded robustly in culture, maintained the
      disease genotype and generated motor neurons that showed selective deficits
      compared to those derived from the child's unaffected mother. This is the first
      study to show that human induced pluripotent stem cells can be used to model the
      specific pathology seen in a genetically inherited disease. As such, it
      represents a promising resource to study disease mechanisms, screen new drug
      compounds and develop new therapies.

PMID- 19098895
TI  - Nodal signalling is involved in left-right asymmetry in snails.
AB  - Many animals display specific internal or external features with left-right
      asymmetry. In vertebrates, the molecular pathway that leads to this asymmetry
      uses the signalling molecule Nodal, a member of the transforming growth factor
      beta superfamily, which is expressed in the left lateral plate mesoderm, and loss
      of nodal function produces a randomization of the left-right asymmetry of
      visceral organs. Orthologues of nodal have also been described in other
      deuterostomes, including ascidians and sea urchins, but no nodal orthologue has
      been reported in the other two main clades of Bilateria: Ecdysozoa (including
      flies and nematodes) and Lophotrochozoa (including snails and annelids). Here we
      report the first evidence for a nodal orthologue in a non-deuterostome group. We
      isolated nodal and Pitx (one of the targets of Nodal signalling) in two species
      of snails and found that the side of the embryo that expresses nodal and Pitx is
      related to body chirality: both genes are expressed on the right side of the
      embryo in the dextral (right-handed) species Lottia gigantea and on the left side
      in the sinistral (left-handed) species Biomphalaria glabrata. We
      pharmacologically inhibited the Nodal pathway and found that nodal acts upstream
      of Pitx, and that some treated animals developed with a loss of shell chirality.
      These results indicate that the involvement of the Nodal pathway in left-right
      asymmetry might have been an ancestral feature of the Bilateria.

PMID- 19098896
TI  - Artificial nanopores that mimic the transport selectivity of the nuclear pore
      complex.
AB  - Nuclear pore complexes (NPCs) act as effective and robust gateways between the
      nucleus and the cytoplasm, selecting for the passage of particular macromolecules
      across the nuclear envelope. NPCs comprise an elaborate scaffold that defines a
      approximately 30 nm diameter passageway connecting the nucleus and the cytoplasm.
      This scaffold anchors proteins termed 'phenylalanine-glycine' (FG)-nucleoporins,
      the natively disordered domains of which line the passageway and extend into its
      lumen. Passive diffusion through this lined passageway is hindered in a size
      dependent manner. However, transport factors and their cargo-bound complexes
      overcome this restriction by transient binding to the FG-nucleoporins. To test
      whether a simple passageway and a lining of transport-factor-binding FG
      nucleoporins are sufficient for selective transport, we designed a functionalized
      membrane that incorporates just these two elements. Here we demonstrate that this
      membrane functions as a nanoselective filter, efficiently passing transport
      factors and transport-factor-cargo complexes that specifically bind FG
      nucleoporins, while significantly inhibiting the passage of proteins that do not.
      This inhibition is greatly enhanced when transport factor is present.
      Determinants of selectivity include the passageway diameter, the length of the
      nanopore region coated with FG-nucleoporins, the binding strength to FG
      nucleoporins, and the antagonistic effect of transport factors on the passage of
      proteins that do not specifically bind FG-nucleoporins. We show that this
      artificial system faithfully reproduces key features of trafficking through the
      NPC, including transport-factor-mediated cargo import.

PMID- 19098897
TI  - Direct observation of the nanoscale dynamics of membrane lipids in a living cell.
AB  - Cholesterol-mediated lipid interactions are thought to have a functional role in
      many membrane-associated processes such as signalling events. Although several
      experiments indicate their existence, lipid nanodomains ('rafts') remain
      controversial owing to the lack of suitable detection techniques in living cells.
      The controversy is reflected in their putative size of 5-200 nm, spanning the
      range between the extent of a protein complex and the resolution limit of optical
      microscopy. Here we demonstrate the ability of stimulated emission depletion
      (STED) far-field fluorescence nanoscopy to detect single diffusing (lipid)
      molecules in nanosized areas in the plasma membrane of living cells. Tuning of
      the probed area to spot sizes approximately 70-fold below the diffraction barrier
      reveals that unlike phosphoglycerolipids, sphingolipids and
      glycosylphosphatidylinositol-anchored proteins are transiently ( approximately 10
      20 ms) trapped in cholesterol-mediated molecular complexes dwelling within <20-nm
      diameter areas. The non-invasive optical recording of molecular time traces and
      fluctuation data in tunable nanoscale domains is a powerful new approach to study
      the dynamics of biomolecules in living cells.

PMID- 19098898
TI  - Intravascular AAV9 preferentially targets neonatal neurons and adult astrocytes.
AB  - Delivery of genes to the brain and spinal cord across the blood-brain barrier
      (BBB) has not yet been achieved. Here we show that adeno-associated virus (AAV) 9
      injected intravenously bypasses the BBB and efficiently targets cells of the
      central nervous system (CNS). Injection of AAV9-GFP into neonatal mice through
      the facial vein results in extensive transduction of dorsal root ganglia and
      motor neurons throughout the spinal cord and widespread transduction of neurons
      throughout the brain, including the neocortex, hippocampus and cerebellum. In
      adult mice, tail vein injection of AAV9-GFP leads to robust transduction of
      astrocytes throughout the entire CNS, with limited neuronal transduction. This
      approach may enable the development of gene therapies for a range of
      neurodegenerative diseases, such as spinal muscular atrophy, through targeting of
      motor neurons, and amyotrophic lateral sclerosis, through targeting of
      astrocytes. It may also be useful for rapid postnatal genetic manipulations in
      basic neuroscience studies.

PMID- 19098899
TI  - Bead-based profiling of tyrosine kinase phosphorylation identifies SRC as a
      potential target for glioblastoma therapy.
AB  - The aberrant activation of tyrosine kinases represents an important oncogenic
      mechanism, and yet the majority of such events remain undiscovered. Here we
      describe a bead-based method for detecting phosphorylation of both wild-type and
      mutant tyrosine kinases in a multiplexed, high-throughput and low-cost manner.
      With the aim of establishing a tyrosine kinase-activation catalog, we used this
      method to profile 130 human cancer lines. Follow-up experiments on the finding
      that SRC is frequently phosphorylated in glioblastoma cell lines showed that SRC
      is also activated in primary glioblastoma patient samples and that the SRC
      inhibitor dasatinib (Sprycel) inhibits viability and cell migration in vitro and
      tumor growth in vivo. Testing of dasatinib-resistant tyrosine kinase alleles
      confirmed that SRC is indeed the relevant target of dasatinib, which inhibits
      many tyrosine kinases. These studies establish the feasibility of tyrosine kinome
      wide phosphorylation profiling and point to SRC as a possible therapeutic target
      in glioblastoma.

PMID- 19098900
TI  - Topoisomerase IIalpha controls the decatenation checkpoint.
AB  - Topoisomerase II (Topo II) is required to separate intertwined sister chromatids
      before chromosome segregation can occur in mitosis. However, it remains to be
      resolved whether Topo II has any role in checkpoint control. Here we report that
      when phosphorylated, Ser 1524 of Topo IIalpha acts as a binding site for the BRCT
      domain of MDC1 (mediator of DNA damage checkpoint protein-1), thereby recruiting
      MDC1 to chromatin. Although Topo IIalpha-MDC1 interaction is not required for
      checkpoint activation induced by DNA damage, it is required for activation of the
      decatenation checkpoint. Mutation of Ser 1524 results in a defective decatenation
      checkpoint. These results reveal an important role of Topo II in checkpoint
      activation and in the maintenance of genomic stability.

PMID- 19098901
TI  - Mouse differentiating spermatogonia can generate germinal stem cells in vivo.
AB  - In adults, stem cells are responsible for the maintenance of many actively
      renewing tissues, such as haematopoietic, skin, gut and germinal tissues. These
      stem cells can self-renew or be committed to becoming progenitors. Stem-cell
      commitment is thought to be irreversible but in male and female Drosophila
      melanogaster, it was shown recently that differentiating germ cells can revert to
      functional stem cells that can restore germinal lineage. Whether progenitors are
      also able to generate stem cells in mammals remains unknown. Here we show that
      purified mouse spermatogonial progenitors committed to differentiation can
      generate functional germinal stem cells that can repopulate germ-cell-depleted
      testes when transplanted into adult mice. We found that GDNF, a key regulator of
      the stem-cell niche, and FGF2 are able to reprogram in vitro spermatogonial
      progenitors for reverse differentiation. This study supports the emerging concept
      that the stem-cell identity is not restricted in adults to a definite pool of
      cells that self-renew, but that stemness could be acquired by differentiating
      progenitors after tissue injury and throughout life.

PMID- 19098902
TI  - UNC-6 (netrin) orients the invasive membrane of the anchor cell in C. elegans.
AB  - Despite their profound importance in the development of cancer, the extracellular
      cues that target cell invasion through basement membrane barriers remain poorly
      understood. A central obstacle has been the difficulty of studying the
      interactions between invading cells and basement membranes in vivo. Using the
      genetically and visually tractable model of Caenorhabditis elegans anchor cell
      (AC) invasion, we show that UNC-6 (netrin) signalling, a pathway not previously
      implicated in controlling cell invasion in vivo, is a key regulator of this
      process. Site of action studies reveal that before invasion, localized UNC-6
      secretion directs its receptor, UNC-40, to the plasma membrane of the AC, in
      contact with the basement membrane. There, UNC-40 polarizes a specialized
      invasive membrane domain through the enrichment of actin regulators, F-actin and
      phosphatidylinositol 4,5-bisphosphate (PtdIns(4,5)P(2)). Cell ablation
      experiments indicate that UNC-6 promotes the formation of invasive protrusions
      from the AC that break down the basement membrane in response to a subsequent
      vulval cue. Together, these results characterize an invasive membrane domain in
      vivo, and reveal a role for UNC-6 (netrin) in polarizing this domain towards its
      basement membrane target.

PMID- 19098903
TI  - SRF and myocardin regulate LRP-mediated amyloid-beta clearance in brain vascular
      cells.
AB  - Amyloid beta-peptide (Abeta) deposition in cerebral vessels contributes to
      cerebral amyloid angiopathy (CAA) in Alzheimer's disease (AD). Here, we report
      that in AD patients and two mouse models of AD, overexpression of serum response
      factor (SRF) and myocardin (MYOCD) in cerebral vascular smooth muscle cells
      (VSMCs) generates an Abeta non-clearing VSMC phenotype through transactivation of
      sterol regulatory element binding protein-2, which downregulates low density
      lipoprotein receptor-related protein-1, a key Abeta clearance receptor. Hypoxia
      stimulated SRF/MYOCD expression in human cerebral VSMCs and in animal models of
      AD. We suggest that SRF and MYOCD function as a transcriptional switch,
      controlling Abeta cerebrovascular clearance and progression of AD.

PMID- 19098904
TI  - Olfactory behavior and physiology are disrupted in prion protein knockout mice.
AB  - The prion protein PrP(C) is infamous for its role in disease, but its normal
      physiological function remains unknown. Here we found a previously unknown
      behavioral phenotype of Prnp(-/-) mice in an odor-guided task. This phenotype was
      manifest in three Prnp knockout lines on different genetic backgrounds, which
      provides strong evidence that the phenotype is caused by a lack of PrP(C) rather
      than by other genetic factors. Prnp(-/-) mice also showed altered behavior in a
      second olfactory task, suggesting that the phenotype is olfactory specific.
      Furthermore, PrP(C) deficiency affected oscillatory activity in the deep layers
      of the main olfactory bulb, as well as dendrodendritic synaptic transmission
      between olfactory bulb granule and mitral cells. Notably, both the behavioral and
      electrophysiological alterations found in Prnp(-/-) mice were rescued by
      transgenic neuronal-specific expression of PrP(C). These data suggest that PrP(C)
      is important in the normal processing of sensory information by the olfactory
      system.

PMID- 19098905
TI  - Task-specific signal transmission from prefrontal cortex in visual selective
      attention.
AB  - Our voluntary behaviors are thought to be controlled by top-down signals from the
      prefrontal cortex that modulate neural processing in the posterior cortices
      according to the behavioral goal. However, we have insufficient evidence for the
      causal effect of the top-down signals. We applied a single-pulse transcranial
      magnetic stimulation over the human prefrontal cortex and measured the strength
      of the top-down signals as an increase in the efficiency of neural impulse
      transmission. The impulse induced by the stimulation transmitted to different
      posterior visual areas depending on the domain of visual features to which
      subjects attended. We also found that the amount of impulse transmission was
      associated with the level of attentional preparation and the performance of
      visual selective-attention tasks, consistent with the causal role of prefrontal
      top-down signals.

PMID- 19098906
TI  - Bone marrow stromal cells attenuate sepsis via prostaglandin E(2)-dependent
      reprogramming of host macrophages to increase their interleukin-10 production.
AB  - Sepsis causes over 200,000 deaths yearly in the US; better treatments are
      urgently needed. Administering bone marrow stromal cells (BMSCs -- also known as
      mesenchymal stem cells) to mice before or shortly after inducing sepsis by cecal
      ligation and puncture reduced mortality and improved organ function. The
      beneficial effect of BMSCs was eliminated by macrophage depletion or pretreatment
      with antibodies specific for interleukin-10 (IL-10) or IL-10 receptor. Monocytes
      and/or macrophages from septic lungs made more IL-10 when prepared from mice
      treated with BMSCs versus untreated mice. Lipopolysaccharide (LPS)-stimulated
      macrophages produced more IL-10 when cultured with BMSCs, but this effect was
      eliminated if the BMSCs lacked the genes encoding Toll-like receptor 4, myeloid
      differentiation primary response gene-88, tumor necrosis factor (TNF) receptor-1a
      or cyclooxygenase-2. Our results suggest that BMSCs (activated by LPS or TNF
      alpha) reprogram macrophages by releasing prostaglandin E(2) that acts on the
      macrophages through the prostaglandin EP2 and EP4 receptors. Because BMSCs have
      been successfully given to humans and can easily be cultured and might be used
      without human leukocyte antigen matching, we suggest that cultured, banked human
      BMSCs may be effective in treating sepsis in high-risk patient groups.

PMID- 19098907
TI  - Gamma-secretase inhibitors reverse glucocorticoid resistance in T cell acute
      lymphoblastic leukemia.
AB  - Gamma-secretase inhibitors (GSIs) block the activation of the oncogenic protein
      Notch homolog-1 (NOTCH1) in T cell acute lymphoblastic leukemia (T-ALL). However,
      limited antileukemic cytotoxicity and severe gastrointestinal toxicity have
      restricted the clinical application of these targeted drugs. Here we show that
      combination therapy with GSIs plus glucocorticoids can improve the antileukemic
      effects of GSIs and reduce their gut toxicity in vivo. Inhibition of NOTCH1
      signaling in glucocorticoid-resistant T-ALL restored glucocorticoid receptor
      autoupregulation and induced apoptotic cell death through induction of the gene
      encoding BCL-2-like apoptosis initiator-11 (BCL2L11). GSI treatment resulted in
      cell cycle arrest and accumulation of goblet cells in the gut mediated by
      upregulation of the gene encoding the transcription factor Kruppel-like factor-4
      (Klf4), a negative regulator of the cell cycle required for goblet cell
      differentiation. In contrast, glucocorticoid treatment induced transcriptional
      upregulation of cyclin D2 (Ccnd2) and protected mice from developing the
      intestinal goblet cell metaplasia typically induced by inhibition of NOTCH
      signaling with GSIs. These results support a role for glucocorticoids plus GSIs
      in the treatment of glucocorticoid-resistant T-ALL.

PMID- 19098908
TI  - MACC1, a newly identified key regulator of HGF-MET signaling, predicts colon
      cancer metastasis.
AB  - We identified a previously undescribed gene associated with colon cancer by
      genome-wide expression analysis in primary and metastatic carcinomas: metastasis
      associated in colon cancer-1, MACC1. MACC1 expression in tumor specimens is an
      independent prognostic indicator of metastasis formation and metastasis-free
      survival. We show that the gene encoding the hepatocyte growth factor (HGF)
      receptor, MET, is a transcriptional target of MACC1. MACC1 promotes
      proliferation, invasion and HGF-induced scattering of colon cancer cells in cell
      culture and tumor growth and metastasis in mouse models. These phenotypes are
      lost in cells expressing MACC1 mutants lacking the SH3 domain or the proline-rich
      motif. For clinical practice, MACC1 will be useful for the identification of poor
      prognosis subjects with colorectal cancer and is a promising new target for
      intervention in metastasis formation.

PMID- 19098909
TI  - Dcx reexpression reduces subcortical band heterotopia and seizure threshold in an
      animal model of neuronal migration disorder.
AB  - Disorders of neuronal migration can lead to malformations of the cerebral
      neocortex that greatly increase the risk of seizures. It remains untested whether
      malformations caused by disorders in neuronal migration can be reduced by
      reactivating cellular migration and whether such repair can decrease seizure
      risk. Here we show, in a rat model of subcortical band heterotopia (SBH)
      generated by in utero RNA interference of the Dcx gene, that aberrantly
      positioned neurons can be stimulated to migrate by reexpressing Dcx after birth.
      Restarting migration in this way both reduces neocortical malformations and
      restores neuronal patterning. We further find that the capacity to reduce SBH
      continues into early postnatal development. Moreover, intervention after birth
      reduces the convulsant-induced seizure threshold to a level similar to that in
      malformation-free controls. These results suggest that disorders of neuronal
      migration may be eventually treatable by reengaging developmental programs both
      to reduce the size of cortical malformations and to reduce seizure risk.

PMID- 19098910
TI  - Accelerated genetic drift on chromosome X during the human dispersal out of
      Africa.
AB  - Comparisons of chromosome X and the autosomes can illuminate differences in the
      histories of males and females as well as shed light on the forces of natural
      selection. We compared the patterns of variation in these parts of the genome
      using two datasets that we assembled for this study that are both genomic in
      scale. Three independent analyses show that around the time of the dispersal of
      modern humans out of Africa, chromosome X experienced much more genetic drift
      than is expected from the pattern on the autosomes. This is not predicted by
      known episodes of demographic history, and we found no similar patterns
      associated with the dispersals into East Asia and Europe. We conclude that a sex
      biased process that reduced the female effective population size, or an episode
      of natural selection unusually affecting chromosome X, was associated with the
      founding of non-African populations.

PMID- 19098911
TI  - Common variants in the NLRP3 region contribute to Crohn's disease susceptibility.
AB  - We used a candidate gene approach to identify a set of SNPs, located in a
      predicted regulatory region on chromosome 1q44 downstream of NLRP3 (previously
      known as CIAS1 and NALP3) that are associated with Crohn's disease. The
      associations were consistently replicated in four sample sets from individuals of
      European descent. In the combined analysis of all samples (710 father-mother
      child trios, 239 cases and 107 controls), these SNPs were strongly associated
      with risk of Crohn's disease (P(combined) = 3.49 x 10(-9), odds ratio = 1.78,
      confidence interval = 1.47-2.16 for rs10733113), reaching a level consistent with
      the stringent significance thresholds imposed by whole-genome association
      studies. In addition, we observed significant associations between SNPs in the
      associated regions and NLRP3 expression and IL-1beta production. Mutations in
      NLRP3 are known to be responsible for three rare autoinflammatory disorders.
      These results suggest that the NLRP3 region is also implicated in the
      susceptibility of more common inflammatory diseases such as Crohn's disease.

PMID- 19098912
TI  - Heritable somatic methylation and inactivation of MSH2 in families with Lynch
      syndrome due to deletion of the 3' exons of TACSTD1.
AB  - Lynch syndrome patients are susceptible to colorectal and endometrial cancers
      owing to inactivating germline mutations in mismatch repair genes, including MSH2
      (ref. 1). Here we describe patients from Dutch and Chinese families with MSH2
      deficient tumors carrying heterozygous germline deletions of the last exons of
      TACSTD1, a gene directly upstream of MSH2 encoding Ep-CAM. Due to these
      deletions, transcription of TACSTD1 extends into MSH2. The MSH2 promoter in cis
      with the deletion is methylated in Ep-CAM positive but not in Ep-CAM negative
      normal tissues, thus revealing a correlation between activity of the mutated
      TACSTD1 allele and epigenetic inactivation of the corresponding MSH2 allele. Gene
      silencing by transcriptional read-through of a neighboring gene in either sense,
      as demonstrated here, or antisense direction, could represent a general
      mutational mechanism. Depending on the expression pattern of the neighboring gene
      that lacks its normal polyadenylation signal, this may cause either generalized
      or mosaic patterns of epigenetic inactivation.

PMID- 19098913
TI  - The lysine demethylase LSD1 (KDM1) is required for maintenance of global DNA
      methylation.
AB  - Histone methylation and DNA methylation cooperatively regulate chromatin
      structure and gene activity. How these two systems coordinate with each other
      remains unclear. Here we study the biological function of lysine-specific
      demethylase 1 (LSD1, also known as KDM1 and AOF2), which has been shown to
      demethylate histone H3 on lysine 4 (H3K4) and lysine 9 (H3K9). We show that LSD1
      is required for gastrulation during mouse embryogenesis. Notably, targeted
      deletion of the gene encoding LSD1 (namely, Aof2) in embryonic stem (ES) cells
      induces progressive loss of DNA methylation. This loss correlates with a decrease
      in DNA methyltransferase 1 (Dnmt1) protein, as a result of reduced Dnmt1
      stability. Dnmt1 protein is methylated in vivo, and its methylation is enhanced
      in the absence of LSD1. Furthermore, Dnmt1 can be methylated by Set7/9 (also
      known as KMT7) and demethylated by LSD1 in vitro. Our findings suggest that LSD1
      demethylates and stabilizes Dnmt1, thus providing a previously unknown
      mechanistic link between the histone and DNA methylation systems.

PMID- 19098914
TI  - Tandem array-based expression screens identify host mRNA targets of virus-encoded
      microRNAs.
AB  - MicroRNAs (miRNAs) are short noncoding RNAs of cellular and viral origin that
      post-transcriptionally regulate gene expression through imperfect base pairing to
      their mRNA targets. Because the recognition sequences of miRNAs for their targets
      are short and may be discontinuous, bioinformatic prediction of targets is
      difficult. Here we present an approach to the experimental identification of the
      mRNA targets of miRNAs encoded by the Kaposi's sarcoma-associated herpesvirus
      (KSHV). KSHV encodes 17 miRNAs, derived from 12 pre-miRNAs expressed from a
      single locus during viral latency. We conducted multiple screens that examine
      small changes in transcript abundance under different conditions of miRNA
      expression or inhibition and then searched the identified transcripts for seed
      sequence matches. Using this strategy, we identified BCLAF1, encoding Bcl2
      associated factor, as a target for miR-K5, and further analysis revealed that
      several other KSHV miRNAs also target this gene product. Our results support that
      this type of expression profiling provides a potentially general approach to the
      identification of miRNA targets.

PMID- 19098915
TI  - Structural analysis of ion selectivity in the NaK channel.
AB  - Here we present a detailed characterization of ion binding in the NaK pore using
      the high-resolution structures of NaK in complex with various cations. These
      structures reveal four ion binding sites with similar chemical environments but
      vastly different ion preference. The most nonselective of all is site 3, which is
      formed exclusively by backbone carbonyl oxygen atoms and resides deep within the
      selectivity filter. Additionally, four water molecules in combination with four
      backbone carbonyl oxygen atoms are seen to participate in K(+) and Rb(+) ion
      chelation, at both the external entrance and the vestibule of the NaK filter,
      confirming the channel's preference for an octahedral ligand configuration for
      K(+) and Rb(+) binding. In contrast, Na(+) binding in the NaK filter,
      particularly at site 4, utilizes a pyramidal ligand configuration that requires
      the participation of a water molecule in the cavity. Therefore, the ability of
      the NaK filter to bind both Na(+) and K(+) ions seemingly arises from the ions'
      ability to use the existing environment in unique ways, rather than from any
      structural rearrangements of the filter itself.

PMID- 19098916
TI  - ATP-dependent unwinding of U4/U6 snRNAs by the Brr2 helicase requires the C
      terminus of Prp8.
AB  - The spliceosome is a highly dynamic machine requiring multiple RNA-dependent
      ATPases of the DExD/H-box family. A fundamental unanswered question is how their
      activities are regulated. Brr2 function is necessary for unwinding the U4/U6
      duplex, a step essential for catalytic activation of the spliceosome. Here we
      show that Brr2-dependent dissociation of U4/U6 snRNAs in vitro is activated by a
      fragment from the C terminus of the U5 snRNP protein Prp8. In contrast to its
      helicase-stimulating activity, this fragment inhibits Brr2 U4/U6-dependent ATPase
      activity. Notably, U4/U6 unwinding activity is not stimulated by fragments
      carrying alleles of prp8 that in humans confers an autosomal dominant form of
      retinitis pigmentosa. Because Brr2 activity must be restricted to prevent
      premature catalytic activation, our results have important implications for
      fidelity maintenance in the spliceosome.

PMID- 19098917
TI  - High-resolution structure of the open NaK channel.
AB  - We report the crystal structure of the nonselective cation channel NaK from
      Bacillus cereus at a resolution of 1.6 A. The structure reveals the intracellular
      gate in an open state, as opposed to the closed form reported previously, making
      NaK the only channel for which the three-dimensional structures of both
      conformations are known. Channel opening follows a conserved mechanism of inner
      helix bending using a flexible glycine residue, the gating hinge, seen in MthK
      and most other tetrameric cation channels. Additionally, distinct inter and
      intrasubunit rearrangements involved in channel gating are seen and characterized
      for the first time along with inner helix twisting motions. Furthermore, we
      identify a residue deeper within the cavity of the channel pore, Phe92, which is
      likely to form a constriction point within the open pore, restricting ion flux
      through the channel. Mutating this residue to alanine causes a subsequent
      increase in ion-conduction rates as measured by (86)Rb flux assays. The
      structures of both the open and closed conformations of the NaK channel correlate
      well with those of equivalent K(+) channel conformations, namely MthK and KcsA,
      respectively.

PMID- 19098918
TI  - Inverse coupling in leak and voltage-activated K+ channel gates underlies
      distinct roles in electrical signaling.
AB  - Voltage-activated (Kv) and leak (K(2P)) K(+) channels have key, yet distinct,
      roles in electrical signaling in the nervous system. Here we examine how
      differences in the operation of the activation and slow inactivation pore gates
      of Kv and K(2P) channels underlie their unique roles in electrical signaling. We
      report that (i) leak K(+) channels possess a lower activation gate, (ii) the
      activation gate is an important determinant controlling the conformational
      stability of the K(+) channel pore, (iii) the lower activation and upper slow
      inactivation gates of leak channels cross-talk and (iv) unlike Kv channels, where
      the two gates are negatively coupled, these two gates are positively coupled in
      K(2P) channels. Our results demonstrate how basic thermodynamic properties of the
      K(+) channel pore, particularly conformational stability and coupling between
      gates, underlie the specialized roles of Kv and K(2P) channel families in
      electrical signaling.

PMID- 19098919
TI  - The costimulatory molecule ICOS regulates the expression of c-Maf and IL-21 in
      the development of follicular T helper cells and TH-17 cells.
AB  - The inducible costimulatory molecule ICOS has been suggested to be important in
      the development of interleukin 17 (IL-17)-producing helper T cells (T(H)-17
      cells) and of follicular helper T cells (T(FH) cells). Here we show that ICOS
      deficient mice had no defect in T(H)-17 differentiation but had fewer T(H)-17
      cells after IL-23 stimulation and fewer T(FH) cells. We also show that T(FH)
      cells produced IL-17 and that T(FH) cells in ICOS-deficient mice were defective
      in IL-17 production. Both T(H)-17 and T(FH) cells had higher expression of the
      transcription factor c-Maf. Genetic loss of c-Maf resulted in a defect in IL-21
      production and fewer T(H)-17 and T(FH) cells. Thus our data suggest that ICOS
      induced c-Maf regulates IL-21 production that in turn regulates the expansion of
      T(H)-17 and T(FH) cells.

PMID- 19098920
TI  - Fc receptor gamma-chain, a constitutive component of the IL-3 receptor, is
      required for IL-3-induced IL-4 production in basophils.
AB  - The Fc receptor common gamma-chain (FcRgamma) is a widely expressed adaptor
      bearing an immunoreceptor tyrosine-based activation motif (ITAM) that transduces
      activation signals from various immunoreceptors. We show here that basophils
      lacking FcRgamma developed normally and proliferated efficiently in response to
      interleukin 3 (IL-3) but were very impaired in IL-3-induced production of IL-4
      and in supporting T helper type 2 differentiation. Through its transmembrane
      portion, FcRgamma associated constitutively with the common beta-chain of the IL
      3 receptor and signaled by recruiting the kinase Syk. Retrovirus-mediated
      complementation demonstrated the essential function of the ITAM of FcRgamma in IL
      3 signal transduction. Our results identify a previously unknown mechanism
      whereby FcRgamma functions to 'route' selective cytokine-triggered signals into
      the ITAM-mediated IL-4 production pathway.

PMID- 19098921
TI  - An in vitro microfluidic approach to generating protein-interaction networks.
AB  - We developed an in vitro protein expression and interaction analysis platform
      based on a highly parallel and sensitive microfluidic affinity assay, and used it
      for 14,792 on-chip experiments, which exhaustively measured the protein-protein
      interactions of 43 Streptococcus pneumoniae proteins in quadruplicate. The
      resulting network of 157 interactions was denser than expected based on known
      networks. Analysis of the network revealed previously undescribed physical
      interactions among members of some biochemical pathways.

PMID- 19098922
TI  - Organophosphorus-degrading bacteria: ecology and industrial applications.
AB  - The first organophosphorus (OP) compound-degrading bacterial strain was isolated
      from a paddy field in the Philippines in 1973. Since then, several
      phylogenetically distinct bacteria that can degrade OP by co-metabolism, or use
      OPs as a source of carbon, phosphorus or nitrogen, have been isolated from
      different parts of the world. There is huge potential for industrial applications
      of OP-degrading bacteria. Important advances in our understanding of the
      microbiology, genomics and evolution of OP-degrading bacteria have been made over
      the past four decades, and are discussed in this review.

PMID- 19098924
TI  - Rheumatoid arthritis in a mouse?

PMID- 19098923
TI  - Intracellular pathogenic bacteria and fungi--a case of convergent evolution?
AB  - The bacterium Yersinia pestis and the fungus Cryptococcus neoformans are the
      causative agents of human plague and cryptococcosis, respectively. Both
      microorganisms are facultatively intracellular pathogens. A comparison of their
      pathogenic strategies reveals similar tactics for intracellular survival in Y.
      pestis and C. neoformans despite their genetic unrelatedness. Both organisms can
      survive in environments where they are vulnerable to predation by amoeboid
      protozoal hosts. Here, we propose that the overall similarities in their
      pathogenic strategies are an example of convergent evolution that has solved the
      problem of intracellular survival.

PMID- 19098925
TI  - Potential new drug targets for osteoporosis.
AB  - Osteoporosis is a worldwide health problem with a high prevalence. Agents for the
      treatment of osteoporosis are classified as either antiresorptive or anabolic.
      Antiresorptive agents work by inhibiting the activity of osteoclasts and,
      therefore, reducing bone resorption. Currently available antiresorptive agents
      include bisphosphonates, selective estrogen-receptor modulators, calcitonin and
      estrogen. Various novel antiresorptive agents are in development. Receptor
      activator of nuclear factor kappa B ligand is an important cytokine involved in
      osteoclast activation; denosumab, a fully human monoclonal antibody to this
      molecule, has finished a major fracture trial. Assessment is underway of
      odanacatib--an inhibitor of cathepsin K, which is an osteoclast enzyme required
      for resorption of bone matrix. Glucagon-like peptide 2 is being evaluated for the
      prevention of the nocturnal rise in bone resorption without affecting bone
      formation. Anabolic agents act by stimulating formation of new bone. The only
      anabolic agent currently available in the US is teriparatide--recombinant human
      parathyroid hormone (PTH)(1-34)--and recombinant human PTH(1-84) is available in
      Europe. PTH stimulates osteoblast function and bone formation. Novel anabolic
      agents in development include: antibodies such as sclerostin and dickkopf-1 that
      target molecules involved in Wnt signaling, a pathway that regulates gene
      transcription of proteins that are important for osteoblast function; an
      antagonist to the calcium-sensing receptor; and an activin receptor fusion
      protein, which functions as an activin antagonist and has shown promise as an
      anabolic agent in early human trials.

PMID- 19098926
TI  - The molecular basis of pain and its clinical implications in rheumatology.
AB  - Nociceptive pain in response to peripheral noxious stimuli, and inflammatory pain
      resulting from tissue damage, serve as warnings that normal bodily function
      cannot resume until the stimulus abates or the tissue repairs. Stimuli cause
      numerous receptors, ion channels and other cellular machinery to respond, and
      propagate signals to the central nervous system, where this information is
      processed and perceived as pain. In healthy individuals, tissue damage results in
      physiologic--generally reparative--changes that lead to heightened sensory
      perception and, often, pain. In rheumatic diseases, the joint pain bears much in
      common with chronic inflammatory pain, but the underlying disease state is
      typically much more intricate and no reparative function is evident. Addressing
      the complex pains of rheumatic disease remains an ongoing challenge. Pain
      signaling pathways involve many molecular components that could potentially be
      targets for pharmacotherapeutic intervention, but the complexity of this system
      might also mean that multiple sites must be affected simultaneously to disrupt
      propagation of pain signals. In addition, to be therapeutically viable, pain
      drugs must be safe and not alter tactile sensory function, alertness or cognitive
      function. In this article we review the molecular functions in nociceptive,
      inflammatory and rheumatic pain pathways, and the therapeutic options they might
      offer.

PMID- 19098927
TI  - The role of ADAMTS-7 and ADAMTS-12 in the pathogenesis of arthritis.
AB  - Loss of articular cartilage caused by extracellular matrix breakdown is the
      hallmark of arthritis. Degradative fragments of cartilage oligomeric matrix
      protein (COMP) have been observed in arthritic patients. ADAMTS-7 and ADAMTS-12,
      two members of the ADAMTS (a disintegrin and metalloproteinase with
      thrombospondin motifs) family, have been associated with COMP degradation in
      vitro, and are significantly overexpressed in the cartilage and synovium of
      patients with rheumatoid arthritis. Recent studies have demonstrated the
      importance of COMP degradation by ADAMTS-7 and ADAMTS-12. Specifically, the size
      of COMP fragments generated by ADAMTS-7 or ADAMTS-12 is similar to that of COMP
      degradative fragments seen in arthritic patients. In addition, antibodies against
      ADAMTS-7 or ADAMTS-12 dramatically inhibit tumor necrosis factor-induced and
      interleukin-1beta-induced COMP degradation in cartilage explants. Furthermore,
      suppression of ADAMTS-7 or ADAMTS-12 expression using the small interfering RNA
      silencing approach in human chondrocytes markedly prevents COMP degradation. COMP
      degradation mediated by ADAMTS-7 and ADAMTS-12 is inhibited by alpha(2)
      macroglobulin. More significantly, granulin-epithelin precursor, a newly
      characterized chondrogenic growth factor, disturbs the interaction between COMP
      and ADAMTS-7 and ADAMTS-12, preventing COMP degradation by these enzymes. This
      Review summarizes the evidence demonstrating that ADAMTS-7 and ADAMTS-12 are
      newly identified enzymes responsible for COMP degradation in arthritis, and that
      alpha(2)-macroglobulin and granulin-epithelin precursor represent their
      endogenous inhibitors.

PMID- 19098928
TI  - There's more to life than everyday function: the challenge of measuring social
      role participation in ankylosing spondylitis.
AB  - Symptoms and functional limitations are commonly reported primary outcome
      measures in ankylosing spondylitis (AS); however, participation has not been
      widely evaluated, as reflected by the scarcity of literature on the subject.
      People with AS suggest that participation in social roles (e.g. employment,
      leisure, and relationships with others) is a critical outcome that is often
      adversely affected by the sequelae of the disease and by the demands of managing
      them. Confusion surrounding the concept of 'social role participation' has
      presented difficulties in defining, developing and using participation as an
      outcome measure. Specifically, distinguishing participation in a social role from
      the performance of activities that might be associated with that role is critical
      for measuring participation, as the repertoire of associated activities will vary
      between individuals. Furthermore, considering which roles are important to
      individuals and evaluating their satisfaction with participating in a role at the
      times and in the ways they would like are also key elements of this measurement.
      Participation as an outcome measure takes on increased importance in diseases
      such as AS where, in the absence of a cure, the benefits of interventions often
      arise from improvements to patients' quality of life. Participation is a
      predictor of quality of life in diseases other than AS; therefore, evaluating
      social role participation, understanding the factors that affect it, and
      intervening to prevent or alleviate participation restrictions will be critical
      for people with AS.

PMID- 19098929
TI  - A case of childhood-onset ankylosing spondylitis: diagnosis and treatment.
AB  - BACKGROUND: A 14-year-old boy with a 6-year history of recurrent arthritis and
      enthesitis, which had not responded to previous treatment with NSAIDs,
      sulfasalazine and methotrexate, presented with a severe flare of these symptoms
      as well as spinal and sacroiliac joint pain. The patient's father had mild
      psoriasis. INVESTIGATIONS: Counts of tender and swollen joints and tender
      entheses; assessment of spinal mobility; assessments using the Childhood Health
      Assessment Questionnaire and the Bath Ankylosing Spondylitis Disease Activity and
      Functional Indices; measurement of erythrocyte sedimentation rate, serum C
      reactive protein level and human leukocyte antigen B27 positivity; radiographs of
      the sacroiliac joints, hips and feet. DIAGNOSIS: Juvenile-onset ankylosing
      spondylitis according to the modified New York criteria for ankylosing
      spondylitis, on the basis of the presence of inflammatory back pain, reduced
      mobility of the spine and grade 3 bilateral radiographic sacroiliitis.
      MANAGEMENT: Treatment with NSAIDs, sulfasalazine and methotrexate did not improve
      the patient's symptoms. Administration of infliximab 5 mg/kg induced a
      substantial and rapid improvement in all parameters of disease activity.

PMID- 19098933
TI  - Editorial and introduction to Asian Journal of Andrology Prostate Cancer special
      issue.

PMID- 19098935
TI  - Cardioprotection by polysaccharide sulfate against ischemia/reperfusion injury in
      isolated rat hearts.
AB  - AIM: Polysaccharide sulfate (PSS) is a new type of heparinoid synthesized with
      alginic acid as the basic material and then by chemical introduction of effective
      groups. Although PSS is successfully applied in ischemic cardio-cerebrovascular
      disease, its effect on cardiac function after ischemia/reperfusion (I/R) injury
      has previously not been investigated. The aim of the present study was to
      investigate whether PSS can protect the heart from I/R injury and the underlying
      mechanism of protection. METHODS: Isolated rat hearts were perfused (Langendorff)
      and subjected to 20 min global ischemia followed by 60 min reperfusion with
      Kreb's Henseleit solution or PSS (0.3-100 mg/L). Myocardial contractile function
      was continuously recorded. Creatine kinase (CK) and lactate dehydrogenase (LDH)
      leakage were measured. Tumor necrosis factor-alpha (TNF-alpha) expression in
      cardiomyocytes was investigated. Western blot analysis for extracellular
      regulated kinases (ERKs), c-jun amino-terminal kinase (JNKs) and p38 mitogen
      activated protein kinase (MAPK) activity was performed. RESULTS: After I/R,
      cardiac contractility decreased, CK and LDH levels increased in the coronary
      effluent, and TNF-alpha expression increased in cardiomyocytes. PSS
      administration at concentrations of 1-30 mg/L improved cardiac contractility,
      reduced CK and LDH release and inhibited TNF-alpha production. Phosphorylated
      p38MAPK (p-p38MAPK) and p-p54/p46-JNK increased in I/R rat hearts but diminished
      in PSS (1-30 mg/L) treated hearts. P-p44/p42-ERK levels were unchanged. In
      contrast, high concentrations of PSS (100 mg/L) had adverse effects that caused a
      worsening of heart function. CONCLUSION: PSS has dose-dependent cardioprotective
      effects on the rat heart after I/R injury. The beneficial effects may be mediated
      through normalization of the activity of p38 MAPK and JNK pathways as well as
      controlling the level of TNF-alpha expression.

PMID- 19098932
TI  - The diverse and contrasting effects of using human prostate cancer cell lines to
      study androgen receptor roles in prostate cancer.
AB  - The androgen receptor (AR) plays an important role in the development and
      progression of prostate cancer (PCa). Androgen deprivation therapy is initially
      effective in blocking tumor growth, but it eventually leads to the hormone
      refractory state. The detailed mechanisms of the conversion from androgen
      dependence to androgen independence remain unclear. Several PCa cell lines were
      established to study the role of AR in PCa, but the results were often
      inconsistent or contrasting in different cell lines, or in the same cell line
      grown under different conditions. The cellular and molecular alteration of
      epithelial cells and their microenvironments are complicated, and it is difficult
      to use a single cell line to address this important issue and also to study the
      pathophysiological effects of AR. In this paper, we summarize the different
      effects of AR on multiple cell lines and show the disadvantages of using a single
      human PCa cell line to study AR effects on PCa. We also discuss the advantages of
      widely used epithelium-stroma co-culture systems, xenograft mouse models, and
      genetically engineered PCa mouse models. The combination of in vitro cell line
      studies and in vivo mouse models might lead to more credible results and better
      strategies for the study of AR roles in PCa.

PMID- 19098934
TI  - Stroma-epithelium crosstalk in prostate cancer.
AB  - The critical role played by stroma-epithelium crosstalk in carcinogenesis and
      progression of prostate cancer has been increasingly recognized. These
      interactions are mediated by a variety of paracrine factors secreted by cancer
      cells and/or stromal cells. In human prostate cancer, reactive stroma is
      characterized by an increase in myofibroblasts and a corresponding amplification
      of extracellular matrix production and angiogenesis. Permanent genetic mutations
      have been reported in stromal cells as well as in tumour cells. Transforming
      growth factor-beta, vascular endothelial growth factor, platelet-derived growth
      factor and fibroblast growth factor signalling pathways are involved in the
      process of angiogenesis, whereas hepatocyte growth factor, insulin-like growth
      factor-1, epidermal growth factor, CXC12 and Interleukin-6 play active roles in
      the progression, androgen-independent conversion and distal metastasis of
      prostate cancer. Some soluble factors have reciprocal interactions with androgens
      and the androgen receptor (AR), and can even activate AR in the absence of the
      androgen ligand. In this article, we review the complex interactions between
      cancer cells and the surrounding microenvironment, and discuss the potential
      therapeutic targets in the stromal compartment of prostate cancer.

PMID- 19098936
TI  - PPAR-gamma agonists inhibit TGF-beta1-induced chemokine expression in human
      tubular epithelial cells.
AB  - AIM: Peroxisome proliferator-activated receptor-gamma (PPAR-gamma) has a wide
      range of biological functions, including anti-inflammation. In this study, we
      investigated the inhibitory effects of PPAR-gamma on transforming growth factor
      beta1 (TGF-beta1)-induced interleukin-8 (IL-8) and monocyte chemoattractant
      protein-1 (MCP-1) expression in renal tubular epithelial cells (HK-2). METHODS:
      HK-2 cells were pretreated with 15d-PGJ2 or troglitazone (TGL) and then treated
      with TGF-beta1. Expression of MCP-1 and IL-8 was measured using real-time PCR and
      ELISA. RESULTS: Treatment with 5 ng/mL TGF-beta1 for 24 h increased both MCP-1
      and IL-8 mRNA and protein levels in HK-2 cells. Both 15d-PGJ2 at 2.5 and 5
      micromol/L and TGL at 2.5 micromol/L exhibited inhibitory effects on TGF-beta1
      induced MCP-1 expression. Additionally, 15d-PGJ2 at 2.5 and 5 micromol/L and TGL
      at 2.5 micromol/L inhibited TGF-beta1-induced expression of IL-8. CONCLUSION:
      PPAR-gamma agonists (15d-PGJ2 and TGL) could inhibit the TGF-beta1-induced
      expression of chemokines in HK-2 cells. Our results suggest that PPAR-gamma
      agonists have the potential to be used as a treatment regimen to reduce
      inflammation in renal tubulointerstitial disease.

PMID- 19098938
TI  - A letter to Darwin.

PMID- 19098939
TI  - The good, the bad and the ugly red tape of biomedical research. How could
      regulators lower bureaucratic hurdles in clinical research without compromising
      the safety of patients?

PMID- 19098940
TI  - Reading the metabolic fine print. The application of metabolomics to diagnostics,
      drug research and nutrition might be integral to improved health and personalized
      medicine.

PMID- 19098937
TI  - In vitro anticancer property of a novel thalidomide analogue through inhibition
      of NF-kappaB activation in HL-60 cells.
AB  - AIM: To investigate the anticancer property and possible mechanism of action of a
      novel sugar-substituted thalidomide derivative (STA-35) on HL-60 cells in vitro.
      METHODS: TNF-alpha-induced NF-kappaB activation was determined using a reporter
      gene assay. The MTT assay was used to measure cytotoxicity of the compound. The
      appearance of apoptotic Sub-G1 cells was detected by flow cytometry analysis.
      PARP cleavage and protein expression of NF-kappaB p65 and its inhibitor IkappaB
      were viewed by Western blotting. RESULTS: TA-35 (1-20 micromol/L) suppressed TNF
      alpha-induced NF-kappaB activation in transfected cells (HEK293/pNiFty-SEAP) in a
      dose- (1-20 micromol/L) and time-dependent (0-48 h) manner. It was also shown
      that STA-35 exerted a dose-dependent inhibitory effect on HL-60 cell
      proliferation with an IC(50) value of 9.05 micromol/L. In addition, STA-35
      induced apoptosis in HL-60 cells, as indicated by the appearance of a Sub-G1 peak
      in the cell cycle distribution, as well as poly ADP-ribose polymerase (PARP)
      cleavage. Subsequently, both NF-kappaB p65 and its inhibitor IkappaB gradually
      accumulated in cytoplasmic extracts in a dose- and time-dependent manner,
      indicating the blockage of NF-kappaB translocation induced by TNF-alpha from the
      cytoplasm to the nucleus. CONCLUSION: A novel sugar-substituted thalidomide
      derivative, STA-35, is potent toward HL-60 cells in vitro and induces apoptosis
      by the suppression of NF-kappaB activation.

PMID- 19098941
TI  - The doctor, the pills, the patient, and the actor-spectator paradox.

PMID- 19098942
TI  - Pain assessment in dementia.

PMID- 19098943
TI  - The rise and rise of anaesthesia in New Zealand.

PMID- 19098944
TI  - Medication beliefs and adherence to antidepressants in primary care.
AB  - AIM: The aim of this study was to determine whether patient beliefs about the
      necessity and concerns about medication were associated with adherence among
      those presenting with depression in primary care. METHODS: At the end of a
      routine consultation with their general medical practitioner, patients completed
      questionnaires including measures of beliefs about medication, self reported
      adherence, depression severity, and demographic information. RESULTS: A
      significant relationship between beliefs in the necessity of antidepressants and
      adherence was not found. However, patient concerns with medications were
      positively associated with non-adherence. Where beliefs about the necessity
      outweighed concerns about taking the medication, significantly greater adherence
      was observed. Fewer depressive symptoms were also associated with greater
      adherence. CONCLUSIONS: This study extended prior research on the role of patient
      beliefs in medication adherence for chronic physical health problems by showing
      the belief-adherence relationship in a depressed patient sample. A balance
      between beliefs about the costs and benefits of medication are likely to be
      important in understanding adherence with other medications.

PMID- 19098946
TI  - General practitioners' views on the major psychiatric classification systems.
AB  - AIM: To understand the views of general practitioners on the utility of
      diagnostic schema as used by specialist psychiatrists and principles that would
      increase the value of diagnostic schema to general practitioners. METHOD: A
      postal survey of 1000 vocationally registered general practitioners in New
      Zealand RESULTS: Diagnostic schema such as the DSM-IV and ICD-10 are seldom used
      by general practitioners due primarily to their complexity and a lack of
      familiarity with them. Providing decision support on pharmaceutical treatment,
      appropriate secondary care referrals and improving communication across the
      primary/secondary care divide are principles that should guide the development of
      future diagnostic schema. Integration of schema into existing computerised
      practice management systems is considered a key success factor. CONCLUSION:
      Specialist devised schema fit uncomfortably into general practice. There is need
      for management orientated diagnostic schema that meet the requirements of general
      practitioners.

PMID- 19098945
TI  - The use of the Pain Assessment Checklist for Seniors with Limited Ability to
      Communicate (PACSLAC) by caregivers in dementia care.
AB  - AIM: Pain is often under-detected and under-treated in nonverbal patients with
      severe dementia. PACSLAC is a behavioural assessment tool designed to improve the
      detection of pain in severe dementia. Previous studies on PACSLAC were primarily
      with qualified nurses in Canada and The Netherlands. This pilot study is aimed to
      evaluate the inter-rater reliability of the PACSLAC when it is administrated by
      caregiver staff. METHOD: 50 patients from four dementia care facilities were
      included. For each patient, a PACSLAC rating was completed independently by a
      medical undergraduate researcher and a caregiver following the caregiver attended
      the patient's usual personal care with the researcher observing in close
      proximity. RESULTS: 36 (72%) were female and 14 (28%) were male. The mean age was
      82.9 years (SD=7.2) and the mean MMSE score was 7.5 (SD=7.9). A total of 12
      caregivers participated in the study. The total PACSLAC scores ranged from 1 to
      22 with a mean of 5.7 (SD=4.0). The average percentage of agreement was 0.89 and
      the Pearson correlation coefficient was 0.83 (p<0.01) for the total PASCLAC
      scores rated by the researcher and the caregivers. CONCLUSION: This pilot study
      demonstrated PACSLAC has good inter-rater reliability when it is used by
      caregivers. We believe a baseline PACSLAC could be performed for each patient at
      the time of admission to a dementia care facility and re-administered on regular
      intervals to detect pain-related behaviour and to prompt earlier pain management.
      Future studies with larger samples and collaboration between different centres
      will be useful in providing normative PACSLAC values in New Zealand.

PMID- 19098947
TI  - Experts' views on long-term care in New Zealand.
AB  - AIMS: This study reports findings from the first national survey of long-term
      care opinion leaders in New Zealand. METHODS: Potential respondents were chosen
      purposively based on their knowledge and experience in long-term care policy and
      planning. Questions focused on assessing views regarding long-term care quality,
      financing, services, workforce, organisation, and regulation. The survey was
      administered via Web-based format during May-June 2007. Seventy-three individuals
      responded for an overall response rate of 47.7%. RESULTS: Experts support cost
      sharing, insurance, and individual savings/preparation as supplements to
      predominately government-based financing. They view increased compensation and
      improved work environments as the key to recruiting/retaining paraprofessionals
      and educational assistance and curriculum reform as the key to attracting
      professionals. Most would expand access to home-based support through adoption of
      comprehensive service packages and various navigational aides (e.g. care
      coordination, counselling). Consumer-direction and public payment of family
      members were also deemed desirable. There was a lack of knowledge regarding
      emerging models of culture change/client-centred care in long-term care.
      Promoting quality by advising providers about how to improve quality and
      increasing public availability of comparative provider information was
      highlighted. CONCLUSIONS: There are varying degrees of consensus regarding the
      kinds of solutions to long-term care problems that are viable from a policy
      perspective. Results should help determine how best to improve the current system
      to meet the needs of the growing elderly population.

PMID- 19098948
TI  - Prevalence of vitamin D deficiency among patients attending a multidisciplinary
      tertiary pain clinic.
AB  - AIM: To estimate the prevalence of vitamin D deficiency in a tertiary
      multidisciplinary pain clinic. METHODS: From 14 July 2006 to 30 November 2007,
      the author requested vitamin D status from all patients with chronic persistent
      pain presenting to The Auckland Regional Pain Service (a tertiary
      multidisciplinary pain service). Serum 25-hydroxyvitamin D levels were determined
      by radioassay. RESULTS: Of 177 patients, 3% had 25-hydroxyvitamin D levels less
      than and equal to 17.5 nmol/L--a level associated with osteomalacia, 32% had 25
      hydroxyvitamin D levels =50 nmol/L--a level associated with vitamin D deficiency,
      and 73% had 25-hydroxyvitamin D levels less than and equal to 80 nmol/L.
      CONCLUSIONS: The prevalence of vitamin D deficiency in patients attending a
      multidisciplinary pain clinic is similar to if not less than that of the normal
      New Zealand population. Recent African immigrants and south Asian females are two
      patient groups that are frequently vitamin D deficient. The identification and
      treatment of vitamin D deficiency has the theoretical potential to help a number
      of chronic pain patients. Only a limited number of interventional clinical trials
      have looked at this.

PMID- 19098949
TI  - The effects of seasonal variation of 25-hydroxyvitamin D on diagnosis of vitamin
      D insufficiency.
AB  - AIMS: To explore the effects of seasonal variation on the diagnosis of vitamin D
      sufficiency and to determine whether age, gender, and ethnicity modify these
      effects. METHODS: 21,987 adults had a measurement of serum 25-hydroxyvitamin D
      (25OHD) at Labplus, Auckland City Hospital, between January 2002 and September
      2003, and sine curves were fitted for 25OHD versus day of year to predict the
      25OHD nadir for each individual. RESULTS: 48% (range: 30-63%) of individuals had
      25OHD <50 nmol/L in the month of measurement, but 63% were predicted to have
      25OHD <50 nmol/L in late winter or early spring based on expected seasonal
      variation. The 25OHD levels required to ensure 25OHD levels >50 nmol/L throughout
      the year varied substantially by season (in summer at least 60-75 nmol/L), and
      tended to be higher in men than women, decrease with age, and vary with
      ethnicity. Mean 25OHD levels were very low (<40 nmol/L) in people of Indian,
      Middle Eastern, and African descent. CONCLUSION: Seasonal variation in 25OHD
      affects the diagnosis of vitamin D sufficiency. Clinicians should consider the
      month of sampling when interpreting the results of 25OHD measurements. In New
      Zealand, a summertime 25OHD <60-75 nmol/L is generally required to ensure year
      round 25OHD levels <50 nmol/L.

PMID- 19098950
TI  - Vitamin D insufficiency in New Zealanders during the winter is associated with
      higher parathyroid hormone concentrations: implications for bone health?
AB  - BACKGROUND: Parathyroid hormone concentration (PTH) is elevated in vitamin D
      insufficiency and when prolonged, this condition leads to reduced bone mass and
      possibly osteoporosis. The threshold of 25-hydroxyvitamin D above which PTH
      plateaus, is a criterion often used to define vitamin D adequacy. AIMS: To
      determine whether the higher rates of vitamin D inadequacy reported in the winter
      than summer months in New Zealand also result in higher PTH concentrations. Also
      to explore the relationship between 25-hydroxyvitamin D and PTH concentrations in
      a New Zealand population to determine if a threshold exists for plasma 25
      hydroxyvitamin D concentration. METHODS: Plasma 25-hydroxyvitamin D and PTH
      concentrations were determined in 342 volunteers living in Invercargill and
      Dunedin (latitude 45-46 degrees S) in late summer (February) and early spring
      (October). RESULTS: Mean plasma 25-hydroxyvitamin D concentration was higher in
      the late summer versus early spring (79 vs 51 nmol/L; p<0.001). The lower plasma
      25-hydroxyvitamin D in early spring versus summer was associated with a 0.2
      pmol/L (p<0.001) higher PTH concentration. A threshold of 61 nmol/L was estimated
      for plasma 25-hydroxyvitamin D, above which there was no further decrease in PTH
      concentration. DISCUSSION: The higher PTH concentration in winter than summer
      suggests that the low 25-hydroxyvitamin D concentration in the winter months may
      be having an adverse effect on bone health. Many New Zealanders have 25
      hydroxyvitamin D concentrations less than 62 nmol/L, especially in winter.
      Strategies to improve the vitamin D status of the population such as
      supplementation and food fortification may be needed.

PMID- 19098951
TI  - Defensive practice in mental health.
AB  - AIM: This study aimed to assess the extent of defensive clinical practice by
      psychiatrists and psychiatric nurses in a New Zealand Mental Health Service.
      METHOD: An anonymous questionnaire survey, addressing perceptions of a variety of
      defensive practices, was sent to all psychiatrists and psychiatric nurses working
      in acute clinical settings in the publically funded mental health service in
      Dunedin, New Zealand. RESULTS: Defensive practice is perceived as widespread in
      psychiatric settings. In particular, practices such as questioning patients about
      their safety, admissions to hospital, and delayed discharge from hospital were
      often perceived as occurring for defensive purposes. Psychiatric nurses were more
      likely than psychiatrists to perceive such practices as defensive. CONCLUSION:
      Defensive practice is common in mental health. This is despite New Zealand's no
      fault compensation scheme, and so presumably results from concerns other than the
      risk of financial liability. There may be particular pressures in mental health
      to practice defensively.

PMID- 19098952
TI  - Telling the truth to Asian patients in the hospital setting.
AB  - Full disclosure of health information to patients is considered important in
      Western culture, but may be less appropriate for patients from other cultures,
      particularly when conveying news about a diagnosis with a poor prognosis. This
      issue is becoming important in New Zealand, given the rapidly increasing ethnic
      diversity of patients presenting to our hospitals. This paper explores culturally
      appropriate ways of breaking bad news to patients of different ethnicities in the
      hospital setting, with emphasis on identifying the locus of decision-making
      within families and decision-making about end-of-life care. Given that the most
      rapid population growth is presently occurring in the Asian community, attention
      is focussed on culturally sensitive ways of breaking bad news to Asian patients
      and their families.

PMID- 19098953
TI  - Inquiries into health care: learning or lynching?
AB  - There is a spectrum of reasons for inquiries into health care: learning,
      catharsis, reassurance, and accountability. The tension is immediately obvious.
      Is the primary purpose learning or lynching? We need to learn from major health
      inquiries. New Zealand needs a culture of inquiry that encourages health
      professionals to discuss their concerns. We need mechanisms that enable health
      professionals to share, learn, and implement changes for improvement. We need
      processes that support more informed scrutiny of health service quality by the
      public and media. There will continue to be a place for inquiries by the HDC and
      Coroners where external scrutiny is necessary.

PMID- 19098954
TI  - Acanthamoeba keratitis associated with cosmetic contact lens wear.

PMID- 19098955
TI  - Catastrophic antiphospholipid syndrome in a 77-year-old man.

PMID- 19098956
TI  - Medical image. Left forearm ecchymosis.

PMID- 19098957
TI  - Eric Anson, anaesthetist.
AB  - Dr Eric Anson was New Zealand's first specialist anaesthetist. Following his
      father's footsteps, his basic and advanced medical training were done in England.
      He served in the Royal Navy in World War I and in the New Zealand Army Medical
      Corps in World War II, both in Egypt and on the hospital ship Oranje. Between the
      wars he was a key figure in the New Zealand Branch of the British Medical
      Association. Dr Anson was Director of Anaesthesia to the Auckland Hospitals from
      late 1945 until 1957. He played major roles in the development of anaesthesia in
      New Zealand, being the first President of the New Zealand Society of
      Anaesthetists (NZSA) and a member of the NZ Committee of the Faculty of
      Anaesthetists in the Royal Australasian College of Surgeons (now the Australian
      and New Zealand College of Anaesthetists). He is remembered by the Anson Memorial
      Foundation in the NZSA.

PMID- 19098958
TI  - Fatal allergic reactions to antibiotics.

PMID- 19098960
TI  - A second opinion.

PMID- 19098959
TI  - Most New Zealand smokers support having fire-safe cigarettes: national survey
      data.

PMID- 19098961
TI  - Men and health.

PMID- 19098962
TI  - Doctoring New Zealand's gay men.
AB  - AIMS: To investigate gay men's experiences of using general practitioner (GP)
      services. METHODS: A qualitative research methodology was used and transcripts
      obtained from 11 focus groups conducted in two large New Zealand cities were
      thematically analysed. RESULTS: The key result is concerned with how men attempt
      to access high quality GP services. Participants reported two main ways they
      achieve this. The first is through selection of a doctor; the second is through
      controlling disclosure of their sexuality to the doctor. We also report
      participants' positive and negative experiences of primary healthcare.
      CONCLUSION: While many men reported good healthcare experiences, others did not.
      To optimise quality of care, gay men carefully managed their relationship with
      their doctors. Doctors play a crucial role in facilitating an environment to
      allow disclosure. While a minority of men have disclosed sexuality and sexual
      behaviours to their doctors, most men have not--arguably to the detriment of
      their healthcare. We argue that doctors need to be cognisant of the health needs
      of gay men to provide high quality care, and we conclude that medical
      practitioners and associations and gay men need to jointly address these issues.

PMID- 19098963
TI  - A 12-year review of gunshot injuries: Auckland City Hospital experience.
AB  - OBJECTIVE: To review gunshot injuries treated in Auckland City Hospital
      (Auckland, New Zealand) over 12 years (1995-2006) and to determine their intent,
      incidence, presentation, severity of injuries, and outcome. METHODS:
      Retrospective review of patients with gunshot wounds (GSW) identified from the
      Auckland City Hospital Trauma registry over the 12-year period 1995-2006.
      RESULTS: A cohort of 56 patients was identified. The majority of patients were
      male (91%). Fifty-two percent of patients suffered accidental injuries. The
      average age of the victims was 32. In the final outcome, 4 (7%) patients died,
      all due to GSW to the head, while all others were discharged alive. CONCLUSION:
      Gunshot injury is not a common presentation to Auckland City Hospital, the
      largest metropolitan hospital in New Zealand. Despite the small number of
      patients presented, the overall outcomes remain acceptable.

PMID- 19098964
TI  - Management of low-velocity, non-gunshot-wound penetrating abdominal injury: have
      we moved with the times?
AB  - BACKGROUND: The incidence of penetrating abdominal injuries in Australia and New
      Zealand is low. Traditionally, low-velocity, non-gunshot-wound (GSW) penetrating
      abdominal injuries have been surgically explored. With advances in imaging
      modalities and laparoscopic techniques, more options now exist to determine the
      presence or absence of serious intra-abdominal injury. Surgical intervention can
      often be avoided. We undertook this study to determine whether these options had
      been reflected in surgical practice and management changed in this population of
      patients. METHODS: Retrospective review of trauma patients over the 10-year
      duration 1996-2005 admitted to Auckland City Hospital Trauma Services. The
      population of patients were subdivided into two cohorts, an earlier group (1996
      2000) and a later group (2001-2005) for comparison purposes. RESULTS: No
      statistical significance existed between the two groups in their demographics and
      treatment approaches. CONCLUSIONS: Despite the availability of laparoscopic
      procedures and advanced imaging techniques, surgical practice in a major
      metropolitan New Zealand hospital had not changed. This may reflect both the
      success of the earlier treatment guidelines and failure of educational strategies
      to effect change of practice.

PMID- 19098965
TI  - Robot-assisted laparoscopic radical prostatectomy (RALP)--a new surgical
      treatment for cancer of the prostate.
AB  - AIM: To examine the safety and efficacy of robotic-assisted laparoscopic
      prostatectomy (RALP) in the early cases of this new technique from a single
      institution. METHOD: A prospective database was created to monitor perioperative
      and postoperative outcomes of men undergoing RALP for clinically localised
      carcinoma of the prostate. RESULTS: The first 30 consecutive cases were followed
      prospectively. There were no conversions to open surgery, perioperative
      transfusions, re-operations, or major complications. The mean operating time was
      280 minutes, with reductions in time between cases 1-10 and 10-20, and a smaller
      improvement between cases 10-20 and 20-30. The mean hospital stay was 1.4 days.
      There was one delayed discharge (4 days) due to an acute anxiety event. One
      patient required readmission for severe bladder spasm, and one patient had a
      failed trial of removal of catheter requiring re-catheterisation. One patient had
      a minor wound infection. The majority of patients had moderately-well
      differentiated, organ-confined disease on specimen histology. CONCLUSION: The
      early results suggest that RALP is a safe and oncologically effective procedure.
      The local results are at least comparable with other early series in the
      literature. It is an important addition to the armamentarium available for
      treating prostate cancer in New Zealand.

PMID- 19098966
TI  - A prospective study analysing the effect of pain on probe insertion, and the
      biopsy strategy, on the patients' perception of pain during TRUS-guided biopsy of
      the prostate.
AB  - OBJECTIVES: PSA testing has led to an increasing number of TRUS-guided biopsies
      being performed. These are well tolerated in the majority, but a minority of men
      find the procedure unacceptably painful. We have studied a cohort of men
      undergoing TRUS guided prostate biopsy to ascertain whether the biopsy strategy,
      or pain on probe insertion, can assist in predicting those who men most likely to
      suffer severe pain during prostate biopsy. METHODS: 162 men (screened and
      symptomatic) between 47 and 86 years of age (mean age 61.7 yrs) who attended for
      TRUS and biopsy were studied. The number of cores taken were governed by TRUS
      volume, less than and equal to <or=30cc = 6 cores, 30.1-39.9cc = 7-11 cores and
      greater than and equal to >or=40cc =12 cores. Each completed a 10-point visual
      analogue pain score (VAS) immediately after procedure. All men were asked to
      describe their pain, on insertion of the TRUS probe, followed by the first and
      the last biopsy. All biopsies were taken with an 18G spring-loaded Tru-cut
      disposable needle. Severe pain (score of 8-10) was deemed unacceptable. RESULTS:
      22% (36/162) of the men biopsied experienced unacceptable pain in one or more of
      the three categories. There was a higher incidence of severe pain in those
      undergoing 12 cores compared to 7-11, or a standard sextant strategy (p=0.05, Chi
      squared for linear trend). Severe pain was experienced by 6% (9/162) of men
      during probe insertion. Of this group 78% (7/9) also went on to find biopsies
      unacceptably painful, compared to 19% (29/152) of those who did not experience
      severe pain for probe insertion (p<0.0001, exact test for two independent
      proportions). CONCLUSIONS: Approximately 1 in 5 men experience unacceptable pain
      at some time during TRUS biopsy of the prostate. A high proportion of men (78%)
      in whom insertion of the TRUS probe was unacceptably painful, found subsequent
      biopsies equally painful. With trend towards saturation biopsies the need for
      predicting group of men who will need local/general anaesthesia is ever
      increasing.

PMID- 19098967
TI  - Who goes to a sexual health clinic? Gender differences in service utilisation.
AB  - AIM: Our aim was to review utilisation of the Hamilton Sexual Health Clinic
      (Hamilton, Waikato, New Zealand) with regard to gender differences. METHODS:
      Notes of those attending during 9 months (1 February 2008-31 October 2008) were
      reviewed--and their demographic details, source of referral, reasons for
      attending, and diagnostic coding data were compared. In addition, Waikato
      Hospital laboratory provided Chlamydia trachomatis test results for the study
      period. Data was analysed for gender differences. RESULTS: Overall, more women
      attended than men. By age bands, more 15-19 year old women than men attended
      (23.3% vs 12.5%, p<0.001) but, for all age-bands 20 years and older, men were at
      least as likely to attend as women. Further, for those aged 25-29 years (20.3% vs
      17%, p<0.5) and 45 years and older (11.9% vs 7.4%, p<0.001), more men than women
      of the same-age band were seen. Men who attended were more likely to self-refer
      (58.5% vs 43%, p<0.001) and less likely to be asymptomatic (30.3% vs 38.4%,
      p<0.001). CONCLUSIONS: Our data suggest men aged 20 years and older are at least,
      if not more, likely than women to attend a sexual health clinic for sexual health
      concerns. However, there appears to be under-utilisation by younger men. To
      improve sexual health for men and women, help-seeking must be timely and
      effective. We need to better understand and address sexual healthcare barriers
      for young men.

PMID- 19098968
TI  - Declining sperm quality in New Zealand over 20 years.
AB  - AIM: To investigate whether semen quality has changed in New Zealand over the
      last 20 years. METHOD: A retrospective study from 1987 to 2007. The sperm
      concentration, volume of seminal fluid, and the percentage of motile sperm were
      analysed from the first semen sample of 975 men presenting as sperm donors in
      Auckland and Wellington. RESULTS: Linear regression showed that the mean
      concentration of sperm decreased from 110 x 10(6) per millilitre in 1987 to 50 x
      10(6) per millilitre in 2007 (p<0.001); an average reduction of 2.5% annually.
      The volume of semen also fell significantly from 3.7 ml to 3.3 ml (p<0.001).
      There was no concomitant change in the duration of abstinence. CONCLUSION: The
      decline in semen volume and sperm concentration in men presenting as sperm donors
      may indicate a reduction in the semen quality of New Zealand men over the past 20
      years.

PMID- 19098969
TI  - PSA testing and DRE, TRUS scanning with sector biopsy, improved histology,
      curative treatments, and active surveillance for prostate cancer: a success story
      for men's health.
AB  - PSA, DRE, and TRUS sector biopsy have been used clinically internationally for
      almost two decades and have been available in New Zealand since 1993. The
      incidence of prostate cancer has approximately doubled. Many countries especially
      in Western Europe, North America and including Australia report decreases in
      prostate cancer mortality due to this change ranging from 10 to 39%. This has not
      so far occurred in New Zealand, however, and likely reasons for this are
      discussed. They include a negative approach encouraged by the New Zealand
      Guidelines Group and others, and more difficult access to investigations and
      treatments for New Zealand men than other countries. Technological advances in
      TRUS sector biopsy, histological diagnosis, and management are discussed. Changes
      in international prostate cancer mortality data and results from several clinical
      trials are also discussed. It is concluded that the weight of evidence in favour
      of PSA/DRE testing is now overwhelming and that potentially between 200 and 300
      of the 600 men who currently die of prostate cancer in New Zealand could be saved
      by the application of current technology.

PMID- 19098970
TI  - Men's health and the health of the nation.
AB  - The health of the male population is a substantial contributor to the health of
      the nation. In general, men have a poorer health status and lower utilisation of
      health services than women. They have a lower life expectancy and are more likely
      to die from avoidable deaths than women. Men's health is increasingly being
      recognised as a specialty area of health promotion and of clinical practice. Male
      specific approaches may assist in maximising the positive outcome of
      interventions aimed at educating men about their health issues, attracting men
      into seeking clinical services, and establishing and maintaining a gender
      orientation in health services that encourages men to engage. With appropriate
      training and resources, primary health care is ideally placed to provide
      accessible, male-friendly services with lead to reduction in gender inequalities
      in health.

PMID- 19098971
TI  - Hypocalcaemia and hypomagnesaemia: a complication of Crohn's disease.

PMID- 19098972
TI  - MYH-associated polyposis--a new familial colorectal cancer syndrome without a
      family history.

PMID- 19098973
TI  - Medical image. Splenic infarction secondary to subacute infective endocarditis.

PMID- 19098974
TI  - Medical image. Lung metastases in adenocarcinoma.

PMID- 19098975
TI  - A mechanism of reduced sperm count--exposure to endocrine disrupting chemicals.

PMID- 19098976
TI  - Greater regulation of complementary medicine therapists needed.

PMID- 19098977
TI  - Anson and anaesthesia.

PMID- 19098978
TI  - "One ticket to town and just letting you know I have syphilis." Time to replace
      the Health Act 1956?

PMID- 19098979
TI  - Cytotoxicity mechanism of two naphthoquinones (menadione and plumbagin) in
      Saccharomyces cerevisiae.
AB  - BACKGROUND: Quinones are compounds extensively used in studies of oxidative
      stress due to their role in plants as chemicals for defense. These compounds are
      of great interest for pharmacologists and scientists, in general, because several
      cancer chemotherapeutic agents contain the quinone nucleus. However, due to
      differences in structures and diverse pharmacological effects, the exact toxicity
      mechanisms exerted by quinones are far from elucidatation. METHODOLOGY/PRINCIPAL
      FINDINGS: Using Saccharomyces cerevisiae, we evaluated the main mechanisms of
      toxicity of two naphthoquinones, menadione and plumbagin, by determining
      tolerance and oxidative stress biomarkers such as GSH and GSSG, lipid
      peroxidation levels, as well as aconitase activity. The importance of glutathione
      transferases (GST) in quinone detoxification was also addressed. The GSSG/GSH
      ratio showed that menadione seemed to exert its toxicity mainly through the
      generation of ROS while plumbagin acted as an electrophile reacting with GSH.
      However, the results showed that, even by different pathways, both drugs were
      capable of generating oxidative stress through their toxic effects. Our results
      showed that the control strain, BY4741, and the glutathione transferase deficient
      strains (gtt1Delta and gtt2Delta) were sensitive to both compounds. With respect
      to the role of GST isoforms in cellular protection against quinone toxicity, we
      observed that the Gtt2 deficient strain was unable to overcome lipid
      peroxidation, even after a plumbagin pre-treatment, indicating that this
      treatment did not improve tolerance when compared with the wild type strain.
      Cross-tolerance experiments confirmed distinct cytotoxicity mechanisms for these
      naphthoquinones since only a pre-treatment with menadione was able to induce
      acquisition of tolerance against stress with plumbagin. CONCLUSIONS/SIGNIFICANCE:
      These results suggest different responses to menadione and plumbagin which could
      be due to the fact that these compounds use different mechanisms to exert their
      toxicity. In addition, the Gtt2 isoform seemed to act as a general protective
      factor involved in quinone detoxification.

PMID- 19098980
TI  - Role of Cajal bodies and nucleolus in the maturation of the U1 snRNP in
      Arabidopsis.
AB  - BACKGROUND: The biogenesis of spliceosomal snRNPs takes place in both the
      cytoplasm where Sm core proteins are added and snRNAs are modified at the 5' and
      3' termini and in the nucleus where snRNP-specific proteins associate. U1 snRNP
      consists of U1 snRNA, seven Sm proteins and three snRNP-specific proteins, U1
      70K, U1A, and U1C. It has been shown previously that after import to the nucleus
      U2 and U4/U6 snRNP-specific proteins first appear in Cajal bodies (CB) and then
      in splicing speckles. In addition, in cells grown under normal conditions U2, U4,
      U5, and U6 snRNAs/snRNPs are abundant in CBs. Therefore, it has been proposed
      that the final assembly of these spliceosomal snRNPs takes place in this nuclear
      compartment. In contrast, U1 snRNA in both animal and plant cells has rarely been
      found in this nuclear compartment. METHODOLOGY/PRINCIPAL FINDINGS: Here, we
      analysed the subnuclear distribution of Arabidopsis U1 snRNP-specific proteins
      fused to GFP or mRFP in transiently transformed Arabidopsis protoplasts.
      Irrespective of the tag used, U1-70K was exclusively found in the nucleus,
      whereas U1A and U1C were equally distributed between the nucleus and the
      cytoplasm. In the nucleus all three proteins localised to CBs and nucleoli
      although to different extent. Interestingly, we also found that the appearance of
      the three proteins in nuclear speckles differ significantly. U1-70K was mostly
      found in speckles whereas U1A and U1C in approximately 90% of cells showed
      diffuse nucleoplasmic in combination with CBs and nucleolar localisation.
      CONCLUSIONS/SIGNIFICANCE: Our data indicate that CBs and nucleolus are involved
      in the maturation of U1 snRNP. Differences in nuclear accumulation and
      distribution between U1-70K and U1A and U1C proteins may indicate that either U1
      70K or U1A and U1C associate with, or is/are involved, in other nuclear processes
      apart from pre-mRNA splicing.

PMID- 19098981
TI  - Pasteurellaceae ComE1 proteins combine the properties of fibronectin adhesins and
      DNA binding competence proteins.
AB  - A novel fibronectin-binding protein from Pasteurella multocida (PM1665) that
      binds to the fibronectin type III(9-10) modules via two helix-hairpin-helix
      motifs has recently been described [1]. This protein shares homology with
      competence-related DNA-binding and uptake proteins (ComEA and ComE) from Gram
      positive and Gram-negative bacteria. Here, we show that recombinant PM1665 (now
      designated ComE1) also binds to DNA through the same helix-hairpin-helix motifs
      required for fibronectin-binding. This binding to DNA is non sequence-specific
      and is confined to double-stranded DNA. We have cloned and expressed ComE1
      proteins from five members of the Pasteurellaceae in order to further investigate
      the function(s) of these proteins. When expressed as recombinant GST-fusion
      proteins, all of the homologues bound both to fibronectin and to double-stranded
      DNA. Inactivation of the gene encoding the ComE1 homologue in Actinobacillus
      pleuropneumoniae indicates major roles for these proteins in at least two
      processes: natural transformation, and binding of bacteria to fibronectin.

PMID- 19098982
TI  - Epidemiological characteristics of classical scrapie outbreaks in 30 sheep flocks
      in the United Kingdom.
AB  - BACKGROUND: Most previous analyses of scrapie outbreaks have focused on flocks
      run by research institutes, which may not reflect the field situation. Within
      this study, we attempt to rectify this deficit by describing the epidemiological
      characteristics of 30 sheep flocks naturally-infected with classical scrapie, and
      by exploring possible underlying causes of variation in the characteristics
      between flocks, including flock-level prion protein (PrP) genotype profile. In
      total, the study involved PrP genotype data for nearly 8600 animals and over 400
      scrapie cases. METHODOLOGY/PRINCIPAL FINDINGS: We found that most scrapie cases
      were restricted to just two PrP genotypes (ARQ/VRQ and VRQ/VRQ), though two
      flocks had markedly different affected genotypes, despite having similar
      underlying genotype profiles to other flocks of the same breed; we identified
      differences amongst flocks in the age of cases of certain PrP genotypes; we found
      that the age-at-onset of clinical signs depended on peak incidence and flock
      type; we found evidence that purchasing infected animals is an important means of
      introducing scrapie to a flock; we found some evidence that flock-level PrP
      genotype profile and flock size account for variation in outbreak
      characteristics; identified seasonality in cases associated with lambing time in
      certain flocks; and we identified one case that was homozygous for phenylalanine
      at codon 141, a polymorphism associated with a very high risk of atypical
      scrapie, and 28 cases that were heterozygous at this codon.
      CONCLUSIONS/SIGNIFICANCE: This paper presents the largest study to date on
      commercially-run sheep flocks naturally-infected with classical scrapie,
      involving 30 study flocks, more than 400 scrapie cases and over 8500 PrP
      genotypes. We show that some of the observed variation in epidemiological
      characteristics between farms is related to differences in their PrP genotype
      profile; although much remains unexplained and may instead be attributed to the
      stochastic nature of scrapie dynamics.

PMID- 19098984
TI  - Applying aspects of generalizability theory in preliminary validation of the
      Multifacet Interprofessional Collaboration Model (PINCOM).
AB  - OBJECTIVE: Empirical assessment of the Interprofessional Collaboration (IPC)
      model within the framework of Generalizability Theory (GT). DESIGN AND
      PARTICIPANTS: A multifacet data collection design served the purpose of examining
      the relationships between observed indicators representing a defined construct.
      Professionals working with children and adolescents (n=134), in the context of
      mental health care, completed a 48 item questionnaire addressing 12 aspects of
      interprofessional collaboration. RESULTS: Estimated variance components from two
      G-studies are presented. The relative impact of different sources of variance was
      estimated 1) for the full design, and 2) for three groups of informants (schools,
      primary care and specialist services). Differences between groups were found
      regarding the relative impact of the level - and context facets with respect to
      perception of IPC. CONCLUSIONS: The methodology of generalizability theory is
      well suited for data with a complex facet structure as displayed in the present
      study. We recommend researchers to give domain specifications thorough attention
      when measuring IPC.

PMID- 19098983
TI  - A method for the simultaneous estimation of selection intensities in overlapping
      genes.
AB  - Inferring the intensity of positive selection in protein-coding genes is
      important since it is used to shed light on the process of adaptation. Recently,
      it has been reported that overlapping genes, which are ubiquitous in all domains
      of life, seem to exhibit inordinate degrees of positive selection. Here, we
      present a new method for the simultaneous estimation of selection intensities in
      overlapping genes. We show that the appearance of positive selection is caused by
      assuming that selection operates independently on each gene in an overlapping
      pair, thereby ignoring the unique evolutionary constraints on overlapping coding
      regions. Our method uses an exact evolutionary model, thereby voiding the need
      for approximation or intensive computation. We test the method by simulating the
      evolution of overlapping genes of different types as well as under diverse
      evolutionary scenarios. Our results indicate that the independent estimation
      approach leads to the false appearance of positive selection even though the gene
      is in reality subject to negative selection. Finally, we use our method to
      estimate selection in two influenza A genes for which positive selection was
      previously inferred. We find no evidence for positive selection in both cases.

PMID- 19098985
TI  - The growth and tumor suppressors NORE1A and RASSF1A are targets for calpain
      mediated proteolysis.
AB  - BACKGROUND: NORE1A and RASSF1A are growth and tumour suppressors inactivated in a
      variety of cancers. Methylation of NORE1A and RASSF1A promoters is the
      predominant mechanism for downregulation of these proteins; however, other
      mechanisms are likely to exist. METHODOLOGY/PRINCIPAL FINDINGS: Here we describe
      a proteolysis of NORE1A and RASSF1A by calpains as alternative mechanism of their
      downregulation. Extracts of H358 cell line, a human bronchoalveolar carcinoma,
      and H460, a large cell carcinoma, were capable of proteolysis of NORE1A protein
      in the calpain-dependent manner. Likewise, RASSF1A tumor suppressor was
      proteolyzed by the H358 cell extract. Addition of calpain inhibitor to H358 and
      H460 cells growing in tissue culture resulted in re-expression of endogenous
      NORE1A. A survey of 10 human lung tumours revealed that three of them contain an
      activity capable of inducing NORE1A degradation. CONCLUSIONS/SIGNIFICANCE: Thus,
      degradation by calpains is a novel mechanism for downregulation of NORE1A and
      RASSF1A proteins and might be the mechanism allowing cancer cells to escape
      growth suppression.

PMID- 19098986
TI  - Gamma power is phase-locked to posterior alpha activity.
AB  - Neuronal oscillations in various frequency bands have been reported in numerous
      studies in both humans and animals. While it is obvious that these oscillations
      play an important role in cognitive processing, it remains unclear how
      oscillations in various frequency bands interact. In this study we have
      investigated phase to power locking in MEG activity of healthy human subjects at
      rest with their eyes closed. To examine cross-frequency coupling, we have
      computed coherence between the time course of the power in a given frequency band
      and the signal itself within every channel. The time-course of the power was
      calculated using a sliding tapered time window followed by a Fourier transform.
      Our findings show that high-frequency gamma power (30-70 Hz) is phase-locked to
      alpha oscillations (8-13 Hz) in the ongoing MEG signals. The topography of the
      coupling was similar to the topography of the alpha power and was strongest over
      occipital areas. Interestingly, gamma activity per se was not evident in the
      power spectra and only became detectable when studied in relation to the alpha
      phase. Intracranial data from an epileptic subject confirmed these findings
      albeit there was slowing in both the alpha and gamma band. A tentative
      explanation for this phenomenon is that the visual system is inhibited during
      most of the alpha cycle whereas a burst of gamma activity at a specific alpha
      phase (e.g. at troughs) reflects a window of excitability.

PMID- 19098987
TI  - Home range utilisation and territorial behaviour of lions (Panthera leo) on
      Karongwe Game Reserve, South Africa.
AB  - Interventionist conservation management of territorial large carnivores has
      increased in recent years, especially in South Africa. Understanding of spatial
      ecology is an important component of predator conservation and management.
      Spatial patterns are influenced by many, often interacting, factors making
      elucidation of key drivers difficult. We had the opportunity to study a
      simplified system, a single pride of lions (Panthera leo) after reintroduction
      onto the 85 km(2) Karongwe Game Reserve, from 1999-2005, using radio-telemetry.
      In 2002 one male was removed from the paired coalition which had been present for
      the first three years. A second pride and male were in a fenced reserve adjacent
      of them to the east. This made it possible to separate social and resource
      factors in both a coalition and single male scenario, and the driving factors
      these seem to have on spatial ecology. Male ranging behaviour was not affected by
      coalition size, being driven more by resource rather than social factors. The
      females responded to the lions on the adjacent reserve by avoiding the area
      closest to them, therefore females may be more driven by social factors. Home
      range size and the resource response to water are important factors to consider
      when reintroducing lions to a small reserve, and it is hoped that these findings
      lead to other similar studies which will contribute to sound decisions regarding
      the management of lions on small reserves.

PMID- 19098988
TI  - Estimating haplotype frequency and coverage of databases.
AB  - A variety of forensic, population, and disease studies are based on haploid DNA
      (e.g. mitochondrial DNA or Y-chromosome data). For any set of genetic markers
      databases of conventional size will normally contain only a fraction of all
      haplotypes. For several applications, reliable estimates of haplotype
      frequencies, the total number of haplotypes and coverage of the database (the
      probability that the next random haplotype is contained in the database) will be
      useful. We propose different approaches to the problem based on classical methods
      as well as new applications of Principal Component Analysis (PCA). We also
      discuss previous proposals based on saturation curves. Several conclusions can be
      inferred from simulated and real data. First, classical estimates of the fraction
      of unseen haplotypes can be seriously biased. Second, there is no obvious way to
      decide on required sample size based on traditional approaches. Methods based on
      testing of hypotheses or length of confidence intervals may appear artificial
      since no single test or parameter stands out as particularly relevant. Rather the
      coverage may be more relevant since it indicates the percentage of different
      haplotypes that are contained in a database; if the coverage is low, there is a
      considerable chance that the next haplotype to be observed does not appear in the
      database and this indicates that the database needs to be expanded. Finally,
      freeware and example data sets accompany the methods discussed in this paper:
      http://folk.uio.no/thoree/nhap/.

PMID- 19098989
TI  - Seasonal intermittent preventive treatment for the prevention of anaemia and
      malaria in Ghanaian children: a randomized, placebo controlled trial.
AB  - BACKGROUND: Malaria and anaemia are the leading causes of morbidity and mortality
      in children in sub-Saharan Africa. We have investigated the effect of
      intermittent preventive treatment with sulphadoxine-pyrimethamine or artesunate
      plus amodiaquine on anaemia and malaria in children in an area of intense,
      prolonged, seasonal malaria transmission in Ghana. METHODS: 2451 children aged 3
      59 months from 30 villages were individually randomised to receive placebo or
      artesunate plus amodiaquine (AS+AQ) monthly or bimonthly, or sulphadoxine
      pyrimethamine (SP) bimonthly over a period of six months. The primary outcome
      measures were episodes of anaemia (Hb<8.0 g/dl) or malaria detected through
      passive surveillance. FINDINGS: Monthly artesunate plus amodiaquine reduced the
      incidence of malaria by 69% (95% CI: 63%, 74%) and anaemia by 45% (95% CI:
      25%,60%), bimonthly sulphadoxine-pyrimethamine reduced the incidence of malaria
      by 24% (95% CI: 14%,33%) and anaemia by 30% (95% CI: 6%, 49%) and bimonthly
      artesunate plus amodiaquine reduced the incidence of malaria by 17% (95% CI: 6%,
      27%) and anaemia by 32% (95% CI: 7%, 50%) compared to placebo. There were no
      statistically significant reductions in the episodes of all cause or malaria
      specific hospital admissions in any of the intervention groups compared to the
      placebo group. There was no significant increase in the incidence of clinical
      malaria in the post intervention period in children who were >1 year old when
      they received IPTc compared to the placebo group. However the incidence of
      malaria in the post intervention period was higher in children who were <1 year
      old when they received AS+AQ monthly compared to the placebo group.
      INTERPRETATION: IPTc is safe and efficacious in reducing the burden of malaria in
      an area of Ghana with a prolonged, intense malaria transmission season. TRIAL
      REGISTRATION: ClinicalTrials.gov NCT00119132.

PMID- 19098991
TI  - Erratum.
AB  - [This corrects the article on p. in vol. , PMID: 16896390.].

PMID- 19098990
TI  - HCV coinfection associated with slower disease progression in HIV-infected former
      plasma donors naive to ART.
AB  - BACKGROUND: It remains controversial how HCV coinfection influences the disease
      progression during HIV-1 infection. This study aims to define the influence of
      HCV infection on the replication of HIV-1 and the disease progression in HIV
      infected former plasma donors (FPDs) naive to ART. METHODOLOGY/PRINCIPAL
      FINDINGS: 168 HIV-1-infected FPDs were enrolled into a cohort study from Anhui
      province in central China, and thereafter monitored at month 3, 9, 15, 21 and 33.
      Fresh whole blood samples were used for CD4+ T-cell counting. Their plasma
      samples were collected and stored for quantification of HIV-1 viral loads and for
      determination of HCV and Toxoplasma. Out of 168 HIV-infected FBDs, 11.9% (20
      cases), 80.4% (135 cases) and 7.7% (13 cases) were infected with HIV-1 alone, HIV
      1/HCV and HIV/HCV/Toxoplasma, respectively. During the 33-month follow-up, only
      35% (7 out of 20 cases) HIV-1 mono-infected subjects remained their CD4+ T-cell
      counts above 200 cells/microl and retained on the cohort study, which was
      significantly lower than 56% (75 out of 135 cases) for HIV/HCV group and 69% (9
      out of 13 cases) for HIV/HCV/Toxoplasma group (p<0.05). CD4+ T cells in HIV mono
      infection group were consistently lower than that in HIV/HCV group (p = 0.04,
      0.18, 0.03 and 0.04 for baseline, month 9, month 21 and month 33 visit,
      respectively). In accordance with those observations, HIV viral loads in HIV mono
      infection group were consistently higher than that in HIV/HCV group though
      statistical significances were only reached at baseline (p = 0.04).
      CONCLUSIONS/SIGNIFICANCE: These data indicated HCV coinfection with HIV-1 is
      associated with the slower disease progression at the very late stage when
      comparing with HIV-1 mono-infection. The coinfection of Toxoplasma with HIV and
      HCV did not exert additional influence on the disease progression. It will be
      highly interesting to further explore the underlying mechanism for this
      observation in the future.

PMID- 19098992
TI  - SLEEP AND CYTOKINES.

PMID- 19098993
TI  - Bone morphogenetic protein-2: a potential regulator in scleral remodeling.
AB  - PURPOSE: Bone morphogenetic protein 2 (BMP-2) is a member of the main subgroup of
      bone morphogenetic proteins within the transforming growth factor-beta
      superfamily. BMP-2 is involved in numerous cellular functions including
      development, cell proliferation, apoptosis, and extracellular matrix synthesis.
      We examined BMP-2 expression in human scleral fibroblasts (HSF) and assessed the
      effects of recombinant human BMP-2 (rhBMP-2) on HSF proliferation, matrix
      metalloproteinase-2 (MMP-2), and tissue inhibitor of metalloproteinase-2 (TIMP
      2). METHODS: We used confocal fluorescence microscopy (CFM) to study BMP-2
      distribution in HSF cells and frozen human scleral sections. The influence of
      rhBMP-2 on cell proliferation at different concentrations (0 ng/ml, 1 ng/ml, 10
      ng/ml, and 100 ng/ml) was evaluated by the 3-(4, 5-dimethylthiazol-2-yl)-2, 5
      diphenyltetrazolium bromide (MTT) assay. The effects of rhBMP-2 on the cell cycle
      were investigated with flow cytometric analysis. Reverse transcription polymerase
      chain reaction (RT-PCR) and enzyme-linked immunosorbent assay (ELISA) were used
      to examine MMP-2 and TIMP-2 mRNAs and secreted proteins in HSF that were
      incubated with rhBMP-2. RESULTS: BMP-2 protein expression from human sclera was
      confirmed by CFM. Cell proliferation was significantly increased with 100 ng/ml
      rhBMP-2 in a time-dependent manner (p<0.05). The HSF cell cycle moved to the S
      and S+G(2)M phases after rhBMP-2 stimulation at 100 ng/ml compared to normal
      cells (p<0.05). TIMP-2 mRNA levels were significantly increased in HSF incubated
      for 24 h with 100 ng/ml rhBMP-2 (p<0.01). A 48 h incubation with 10 ng/ml or 100
      ng/ml rhBMP-2 resulted in significantly increased TIMP-2 mRNA and protein
      expression and significantly decreased MMP-2 mRNA expression (p<0.01) while MMP-2
      protein expression significantly decreased at 100 ng/ml rhBMP-2 (p<0.01).
      CONCLUSIONS: Human sclera fibroblasts expressed BMP-2, which promoted cell
      proliferation, and elicited changes in MMP-2 and TIMP-2, might influence
      extracellular matrix synthesis.

PMID- 19098994
TI  - Evaluation of LOXL1 polymorphisms in primary open-angle glaucoma in southern and
      northern Chinese.
AB  - PURPOSE: The lysyl oxidase-like protein 1 (LOXL1) gene is strongly associated
      with exfoliation glaucoma, which is very rare in the Chinese population. The
      implicated LOXL1 polymorphisms have not been associated with primary open-angle
      glaucoma (POAG). In this study, we investigated three of the LOXL1 polymorphisms
      in POAG in a southern Chinese population of Hong Kong and northern Chinese from
      Beijing. METHODS: The Hong Kong group included 293 POAG patients and 250
      controls, and the Beijing group included 169 POAG patients and 197 controls.
      LOXL1 single nucleotide polymorphisms (SNPs), rs1048661, rs3825942, and
      rs2165241, were genotyped by direct DNA sequencing. Individual association was
      analyzed using the chi(2) test, and haplotype-based association analysis was
      performed in WHAP. RESULTS: Each of the candidate SNPs was not statistically
      associated with POAG in either group (p>0.017, Bonferroni correction). Haplotype
      based association analysis had identified a significant omnibus association
      (Omnibus chi(2)=18.16, p=0.00115) between these SNPs and POAG in the Hong Kong
      group. A minor haplotype (T-G-T) showed significant statistical association with
      POAG. It presented in 2.1% of cases and 0.4% of controls, conferring a 5.24 fold
      of increased risk to the disease (95% CI: 1.17-23.54, P(perm)=0.00108). However,
      this haplotype was absent in the Beijing group. CONCLUSIONS: Individual LOXL1
      SNPs, rs1048661, rs3825942, and rs2165241, were not associated with POAG in the
      Chinese population. However, a minor haplotype T-G-T was found to be associated
      with the disorder in the southern Chinese. The low frequencies of the at-risk
      alleles at rs1048661 and rs2165241 may be one of the factors that led to the low
      prevalence of exfoliation syndrome in the general populations of the Chinese.

PMID- 19098995
TI  - Differential regulation of Dlg1, Scrib, and Lgl1 expression in a transgenic mouse
      model of ocular cancer.
AB  - PURPOSE: Discs large (dlg), scribble (scrib), and lethal giant larvae (lgl) are
      major suppressor genes in Drosophila melanogaster. They encode proteins that
      regulate cell polarity and cell proliferation in Drosophila and mammals. However,
      their basic oncogenic roles have not yet been established in mouse epithelial
      ocular cancer. We evaluated the potential implication of these proteins in
      tumorigenesis of adenocarcinomas originating from the retinal pigmented
      epithelium of the Trp1/Tag transgenic mouse model. We examined the changes in the
      distribution and levels of these proteins in mouse ocular tissues from the
      Trp1/Tag mouse model. METHODS: The expression patterns of theses genes and their
      corresponding proteins in normal mouse ocular tissues were studied by in situ
      hibridization and immunohistofluorescence experiments. In addition, variations in
      mRNA and proteins levels and protein distributions for Dlg1, Scrib, and Lgl1 were
      analyzed in the ocular tissues from Trp1/Tag transgenic mouse model by reverse
      transcription polymerase chain reaction (RT-PCR), western blot analysis, and
      immunohistofluorescence. RESULTS: We found that mouse Dlg1, Scrib, and Lgl1 are
      widely distributed in normal ocular tissues, particularly in retinal neurons. We
      found that the three proteins are mislocalized in retinal layers during ocular
      carcinogenesis. These mislocalizations were correlated to the early dysplastic
      stages of ocular tumorigenesis. Additionally, the mislocalization of each protein
      was associated with its downregulation. Decreased levels of these proteins may be
      considered as late-stage markers of the disease but also as markers of the
      invasive stage of this cancerous process. This downregulation may be involved in
      epithelial-mesenchymal transition in this mouse ocular tumoral model. This would
      be consistent with the downregulation of E-cadherin and upregulation of N
      cadherin expression observed in this model. CONCLUSIONS: This is the first study
      to demonstrate the involvement of Dlg1, Scrib, and Lgl1 in a mouse with ocular
      adenocarcinoma and the simultaneous involvement of these proteins in the same
      cancer. Our results indicate that both the mislocalization and downregulation of
      these proteins may be involved together in ocular carcinogenesis.

PMID- 19098996
TI  - Proteomic analysis of regenerated rabbit lenses reveal crystallin expression
      characteristic of adult rabbits.
AB  - PURPOSE: To explore lens crystallin characteristics and morphology of rabbit
      regenerated lenses in comparison with wild type natural lenses by means of
      proteomic analysis and histological assay. METHODS: The lens regeneration model
      of the New Zealand rabbit was established, and lens regeneration was observed by
      slit lamp examination and photography. A histological assay was evaluated under
      light microscopy and transmission electron microscopy (TEM). Protein samples of
      regenerated lenses were collected from experimental rabbit eyes 2, 4, and 16
      weeks after surgery. Two-dimensional gel electrophoresis (2-DE) was performed.
      Image analyses was done using the ImageMaster 2D Elite 3.01 software package. The
      protein spots were trypsinized and identified by matrix-assisted laser
      desorption/ionization-time-of-flight-mass spectrometry. RESULTS: Lens
      regeneration began in the periphery of the capsule bag about one to two weeks
      after the surgery and proceeded to regenerate toward the center. The regenerated
      lens appeared spherical in shape with a fairly translucent cortical structure and
      a nuclear opacity. Histological findings showed that the remnant lens epithelial
      cells differentiate at the lens capsule equator and new lens fibers form in a
      concentric pattern in a manner similar to that observed in natural lenses.
      However, TEM showed morphological changes in the epithelial cells of the
      regenerated lenses as compared with natural lenses. 2-D electrophoresis revealed
      that the patterns of protein spots from regenerated lenses (two weeks, four
      weeks, and 16 weeks) were analogous to those of 16-week-old natural lenses but
      were substantially different from those of two-week-old natural lenses,
      particularly when the two-week-old regenerated lenses were compared with the two
      week-old natural lenses. CONCLUSIONS: Proteomic analysis revealed that crystallin
      expression in regenerated rabbit lenses was analogous to that of natural lenses
      of adult rabbits but was different from that of very young rabbits (two weeks
      old), and TEM revealed the presence of morphological changes in the epithelial
      cells of regenerated lenses. These results suggest that the regrowth of lens
      materials in the lens capsule after endocapsular phacoemulsification might
      actually represent the regeneration of "mature" lens substances, which have led
      us to the conclusion that the regenerative process does not exactly mimic
      embryonic development.

PMID- 19098998
TI  - Small papillary tumor in the saccule.
AB  - Papillary tumors of the ear are aggressive neoplasms. Previously, a tumor growing
      in the saccule had not been reported. We report a tumor found incidentally in the
      saccule of a patient. Serial sections of both temporal bones of the patient were
      studied in order to analyze the tumor's origin and influence on audio vestibular
      function. In the right inner ear, there was a small papillary lesion in the
      saccule, which looked like a papillary tumor without aggression invasion. The
      tumor was located in the membranous labyrinth of the saccule, not in the
      endolymphatic duct and sac. It was not related to Von Hippel-Lindau (VHL)
      disease, nor was it an endolymphatic sac tumor. The tumor did not influence the
      hearing and vestibular function in the right ear, although this patient presented
      a severe sensorineural hearing loss and vestibular function loss because of the
      vestibular schwannoma in the left ear.

PMID- 19099002
TI  - Is the clinical advice you give your patients evidence-based?

PMID- 19098997
TI  - Genes involved in viral carcinogenesis and tumor initiation in hepatitis C virus
      induced hepatocellular carcinoma.
AB  - The role of chronic hepatitis C virus (HCV) in the pathogenesis of HCV-associated
      hepatocellular carcinoma (HCC) remains controversial. To understand the
      transition from benign to malignant, we studied the gene expression patterns in
      liver tissues at different stages, including normal, cirrhosis, and different HCC
      stages. We studied 108 liver tissue samples obtained from 88 distinct patients
      (41 HCV-cirrhotic tissues, 17 HCV-cirrhotic tissues from patients with HCC, and
      47 HCV-HCC tissues). Differentially expressed genes (DEG) were studied by use of
      high-density oligonucleotide arrays. Among probe sets identified as
      differentially expressed via the F test, all pairwise comparisons were performed.
      Cirrhotic tissues with and without concomitant HCC were further evaluated, and a
      classifier was used to predict whether the tissue type was associated with HCC.
      Differential expression profiles were analyzed using Interaction Networks and
      Functional Analysis. Characteristic gene signatures were identified when normal
      tissue was compared with cirrhosis, cirrhosis with early HCC, and normal with
      HCC. Pathway analysis classified the cellular and biological functions of the DEG
      as related to cellular growth and proliferation, cell death and inflammatory
      disease in cirrhosis; cell death, cell cycle, DNA replication, and immune
      response in early HCCs; and cell death, cell growth and proliferation, cell
      cycle, and DNA repair in advanced HCCs. Characteristic gene signatures were
      identified at different stages of HCV-HCC progression. A set of genes were
      identified to predict whether the cirrhotic tissue was associated with HCC.

PMID- 19099003
TI  - The doctor of nursing practice: recognizing a need or graying the line between
      doctor and nurse?
AB  - The distinction between doctor and nurse has been historically visible to
      patients, and the scope of practice for each healthcare provider has been clearly
      marked by a wall of separation rooted in state law. In fact, even the titles by
      which these providers have been addressed have remained constant, with the term
      "doctor" being reserved for reference to physicians. With the advent of the new
      doctor of nursing practice degree, however, the clear distinction between doctor
      and nurse is in jeopardy. Moreover, accompanying the push toward a practice
      doctorate for advanced nursing practice is a call for the expansion of the scope
      of advanced nursing practice. The urgent questions at hand are the following:
      First, is a practice doctorate necessary or even appropriate for advanced nursing
      practice? Second, should the scope of advanced nursing practice be extended at
      this time? In addition to the increased educational requirements placed on
      aspiring advanced practice nurses and the associated increase in costs of
      obtaining the requisite education, requiring a practice doctorate for advanced
      practice nursing risks blurring the line between doctor and nurse and creates a
      potential for patient confusion. A true need for requiring a practice doctorate
      for advanced practice nursing has not been demonstrated. Moreover, the states
      should tread carefully when considering expanded roles for advanced practice
      nurses to avoid creating conflict within the medical community. Considering the
      level of qualification of today's medical school applicants, perhaps we should be
      training more physicians to meet the demand head-on rather than creating a
      separate practice doctorate to fill the gap.

PMID- 19099004
TI  - The myth of equipoise in phase 1 clinical trials.
AB  - Phase 1 clinical research trials using healthy volunteers are conducted for the
      sole purpose of serving the public good (a utilitarian concept). The literature
      on equipoise analysis does not exclude phase 1 trials with controls or healthy
      volunteers from the claim of being in "equipoise." The continued perpetuation of
      this ethically and scientifically invalid concept undermines the ethics of
      research with human subjects.

PMID- 19099005
TI  - Passive dissemination of printed educational materials in medicine has no or
      negligible effect on patient outcomes.

PMID- 19099006
TI  - Contrasting Canada and the United States: what did they get right and wrong about
      healthcare?

PMID- 19099007
TI  - Learning what works in healthcare.

PMID- 19099008
TI  - Clinical evidence for rebound hypercoagulability after discontinuing oral
      anticoagulants for venous thromboembolism.
AB  - CONTEXT: In vitro studies and anecdotal clinical reports have suggested that
      clinically significant rebound hypercoagulability may occur after discontinuation
      of oral anticoagulants (OACs), such as vitamin K antagonists and ximelagatran,
      for venous thromboembolism (VTE). OBJECTIVE: Assess the extent to which rebound
      hypercoagulability-related VTE recurrences occur in the 2 months following
      discontinuation of OACs. DATA SOURCES: Published, randomized controlled trials
      (RCTs) of OAC treatment of VTE. STUDY SELECTION: RCTs of varying durations of OAC
      treatment of VTE that include VTE recurrence (or extension) data for more than 2
      months after discontinuation of anticoagulants. DATA EXTRACTION: Rates of VTE
      recurrences (1) while taking OACs, (2) within 2 months of discontinuing OACs, and
      (3) from > 2 months until the end of the study were extracted along with major
      bleeding episodes while on OACs. The rate of VTE recurrences possibly
      attributable to rebound hypercoagulability was estimated by subtracting the VTE
      recurrence rate after the 2-month rebound period from the rate during the rebound
      period. DATA SYNTHESIS: In 20 trials (n = 5822), VTE recurrences were 2.62 times
      as frequent in the 2 months following discontinuation of OACs as subsequently
      (1.57% VTE recurrences per month falling to 0.56% per month, odds ratio = 2.62,
      95% confidence interval: 2.19-3.14), corresponding to 2.02% of patients with
      rebound hypercoagulability-related VTE recurrences (1.57% per month - 0.56% per
      month x 2 months = 2.02%). In the 11 trials with evaluable data from the shorter-
      and longer-duration OAC arms, total adverse events (VTE recurrences plus major
      bleeding) over the entire durations of the trials were not significantly
      different. CONCLUSIONS: Rebound hypercoagulability accounts for about 2% of
      patients having recurrent VTE in the first 2 months after discontinuing OACs.
      RCTs evaluating the efficacy of OACs should include data for at least 2 months
      following OAC treatment. Increasing the duration of OAC treatment does not reduce
      the overall adverse events.

PMID- 19099010
TI  - Epilepsy makes drowning a lot more likely.

PMID- 19099009
TI  - Evaluation of GW406381 for treatment of osteoarthritis of the knee: two
      randomized, controlled studies.
AB  - CONTEXT: GW406381 is an investigational, highly selective cyclooxygenase-2 (COX
      2) inhibitor that is effective in animal models of central sensitization and of
      inflammatory pain. OBJECTIVE: To examine dose response for efficacy and safety of
      GW406381 in adults with osteoarthritis (OA) of the knee. DESIGN: Two randomized,
      double-blind, placebo- and positive-control studies: Study A, a 6-week nonflare
      design; Study B, a 12-week flare design. PATIENTS: 649 patients entered Study A;
      1331 patients entered Study B. INTERVENTIONS:  STUDY A: GW406381 10, 20, 35, or
      50 mg, celecoxib 200 mg, or placebo. Study B: GW406381 1, 5, 10, 25, or 50 mg,
      celecoxib 200 mg, or placebo. MAIN OUTCOME MEASURES: Study A, co-primary
      endpoints were change from baseline in Western Ontario and McMaster Universities
      Osteoarthritis Index (WOMAC) pain subscore and WOMAC question 1. Study B co
      primary endpoints were change from baseline in WOMAC pain and function subscores
      and Patient Global Assessment of Arthritis Condition. A closed hierarchical test
      procedure was prespecified. RESULTS: Study A demonstrated that GW406381 50 mg was
      superior to placebo on WOMAC pain subscore (mean difference from placebo -6.9 mm;
      P= .012). No clear dose response was observed, and the results with celecoxib
      were no different from those of placebo. In Study B, no dose of GW406381 was
      superior to placebo on the co-primary endpoints. Celecoxib was superior to
      placebo on all co-primary endpoints. Dose-related blood pressure and renovascular
      effects were seen with GW406381. CONCLUSIONS: Overall, clinically meaningful
      efficacy in pain related to OA of the knee was not demonstrated for GW406381
      despite its peripheral and central sites of action.

PMID- 19099011
TI  - Influenza: a multipronged approach to protecting our smallest patients.

PMID- 19099012
TI  - Failed connections: why connecting humans is as important as connecting
      computers.

PMID- 19099013
TI  - A case of obscure gastrointestinal bleeding secondary to a small bowel
      gastrointestinal stromal tumor detected by magnetic resonance enterography.

PMID- 19099014
TI  - Multiple drug interactions in a renal transplant patient leading to simvastatin
      induced rhabdomyolysis: a case report.
AB  - Rhabdomyolysis, a syndrome characterized by muscle necrosis with release of toxic
      intracellular muscle constituents, can be a potentially fatal side effect of
      medical therapy. Here I report a patient with a 12-year history of simvastatin
      use who presented with rhabdomyolysis. He had a renal transplant and has been on
      a stable dose of cyclosporine for the past year. Recent medication changes were
      the addition of ranolazine, carvedilol, and diltiazem about two months prior to
      the episode of rhabdomyolysis. Discontinuation of the ranolazine, diltiazem, and
      simvastatin resulted in prompt resolution of the episode. It is suggested that
      these medications, acting in concert with cyclosporine, altered the metabolism of
      simvastatin, causing the episode of rhabdomyolysis. Clinicians should be alert to
      the possibility of multiple drug interactions causing rhabdomyolysis.

PMID- 19099015
TI  - How to make screening mammography less uncomfortable.

PMID- 19099016
TI  - Perforator flaps: a microsurgical innovation.

PMID- 19099017
TI  - The end of peer review and traditional publishing as we know it.

PMID- 19099018
TI  - Preparing medical students for the world: service learning and global health
      justice.
AB  - In this article, we discuss the growth of international service learning in
      undergraduate medical education and tie it to a burgeoning interest among
      students and educators in global health justice. The process of experience,
      reflection, and action is the cornerstone of cultivating a sense of social
      justice among students. Finally, we examine both risks and benefits to
      international service learning for medical students. We define "service
      learning," distinguish it from service and volunteerism, and offer praxis as a
      manifestation of professionalism.

PMID- 19099019
TI  - Supraglottoplasty in infants using sinus instruments.

PMID- 19099020
TI  - The effectiveness of intradialytic exercise prescription on quality of life in
      patients with chronic kidney disease.
AB  - BACKGROUND: Chronic kidney disease (CKD) is a widespread medical condition that
      is progressive in nature. As renal function declines, the disease ultimately
      reaches the life-threatening end stage(ESRD), which requires urgent replacement
      therapy, either by dialysis or transplantation. As a result, CKD patients, many
      of whom have comorbid medical conditions, are severely restricted in physical,
      psychological, and social dimensions of life. Over the past 3 decades, research
      has been carried out on the effects of intradialytic exercise rehabilitation on
      the quality of life (QoL) of CKD patients. AIMS: This review aims to critically
      examine the effect of exercise prescription in reducing the physical and
      psychological limitations encountered by CKD patients. METHOD: Four studies were
      selected and critically appraised using specific inclusion criteria. RESULTS: The
      results of all studies suggest a causal relationship between exercise
      intervention and QoL of CKD patients. Exercising patients have shown improvements
      in physical fitness, psychological function, manual dexterity, reaction times,
      and lower-extremity muscle strength. All of these factors help improve QoL.
      CONCLUSION: Evidence gathered from the studies shows that exercise training has
      beneficial effects on the QoL of CKD patients; however, exercise is still not
      routinely prescribed. Further research and robust evidence are needed to overcome
      the limitations encountered by previous studies to confirm the positive results
      of exercise prescription in management of CKD.

PMID- 19099022
TI  - Readers respond to "Responding to the American siege against continuing medical
      education".

PMID- 19099023
TI  - Doing better for less: the case for organized group practices.

PMID- 19099024
TI  - Precious last moments: family presence during resuscitation.

PMID- 19099025
TI  - Thirty-seven uninterrupted years of hemodialysis: a case report.
AB  - A patient is presented who was on uninterrupted hemodialysis for 37 years. She
      did extremely well for much of her time on hemodialysis. Significant issues that
      occurred included multiple vascular access problems, cardiac arrhythmias,
      osteodystrophy resulting in a fracture of her femur after light trauma, the
      incidental finding of a renal cell carcinoma, and the development of hepatitis C
      positivity. The literature of extremely long-lived patients on uninterrupted
      hemodialysis is reviewed, and the clinical characteristics and complications of
      these patients are discussed.

PMID- 19099026
TI  - Role of human papillomavirus types 16, 18, and 52 in recurrent cystitis and
      urinary bladder cancer among Egyptian patients.
AB  - BACKGROUND: Bladder cancer is a common malignancy in Egypt. Human papillomavirus
      (HPV) could have a possible etiologic role in bladder carcinogenesis. We aimed to
      estimate the prevalence of HPV-16, -18, and -52 in Egyptian patients with bladder
      cancer or recurrent cystitis, and to study the correlation of type-specific HPV
      immunoglobulin (Ig)G with polymerase chain reaction (PCR) results and different
      clinicopathologic parameters. METHODS: This study was conducted on 60 inpatients
      of the Urosurgery Department at the Theodor Bilharz Research Institute (TBRI),
      who were identified histopathologically and clinically as cancer bladder (group
      I, 20 patients), cystitis (group II, 24 patients), and cancer bladder with
      cystitis (group III, 16 patients), and a fourth group of 20 healthy control
      subjects (for serologic testing). Patients were subjected to detection of HPV-16
      and -18 DNA by PCR on bladder tissue biopsies (BTB) and buffy coat cells (BCC)
      and serum IgG antibodies to L1 capsids of HPV-16 and -52 IgG by enzyme-linked
      immunosorbent assay (ELISA). RESULTS: HPV-16 and -18 DNA were detected in BTB
      (30% and 10%, respectively) with significantly higher rates (44.4%) in bladder
      cancer than cystitis cases (11.11%), with significant association with
      schistosomal affection (78.6% and 25%, respectively) and recurrence (48%, HPV
      16). There was a significant association of transitional cell carcinoma (TCC)
      with HPV-16 in 69.2% and 61.1% of BCC and BTB, respectively. Multiple HPV types
      16, 18, and 52 were significantly higher than single types (79.2% and 20.8%,
      respectively). The observed absolute association between seropositivity of HPV-52
      (11.7%) and HPV-16 (26.7%) was significantly associated with TCC in patient
      groups only. CONCLUSION: Our study confirmed the significant association of HPV
      16, -18 and -52 with bladder cancer in Egyptian patients, with the suggestion of
      viral synergistic action in bladder carcinogenesis. Such HPV types were
      significantly associated with TCC tumors of low grade and high stage, with
      schistosomal affection and recurrence tendency. HPV serology would pave the way
      for better management and follow-up of patients and for optimal design and
      evaluation of HPV vaccination.

PMID- 19099027
TI  - Readers' and author's responses to "Physicians for sale: how medical professional
      organizations exploit their members".

PMID- 19099029
TI  - Why and how to use the photographic atlases of the American Registry of
      Pathology.

PMID- 19099030
TI  - The presidential candidates' health reform plans: choices for the nation.

PMID- 19099031
TI  - Incompetent patients, substitute decision making, and quality of life: some
      ethical considerations.
AB  - One of the most difficult situations facing physicians involves decision making
      by substitute decision makers for patients who have never been competent. This
      paper begins with a brief examination of the ethics of substitute decision making
      for previously competent patients. It then applies the results to substitute
      decision making for patients who have never been competent, and critically
      analyzes 5 models of substitute decision making for such patients, showing why
      each either contravenes basic ethical principles or fails to guarantee the use of
      ethically appropriate values. It concludes by sketching a modified objective
      reasonable person standard for substitute decision making that avoids valuational
      difficulties and allows for a protocol that satisfies ethical principles.

PMID- 19099032
TI  - Impact of anthropogenic environmental alterations on vector-borne diseases.
AB  - The spread of infectious vector-borne diseases involves at least 3 organisms: a
      parasite, a vector, and a host. Alterations to the natural environment may change
      the context within which these entities interact, thus potentially affecting
      vector-borne disease epidemiology. In this review, examples are presented in
      which human-driven ecological changes may be contributing to the spread of vector
      borne diseases. Such changes include deforestation, agriculture and animal
      husbandry, water control projects, urbanization, loss of biodiversity,
      introduction of alien species, and climate change. The global environment is
      currently being degraded at an alarming pace, potentially placing human
      populations at increasing risk for unnecessary and preventable outbreaks of
      vector-borne diseases. Further research is needed to improve our ability to
      predict and prevent emergence and reemergence of vector-borne diseases from
      environmental alterations.

PMID- 19099034
TI  - Advance care planning for decisional incapacity: keep it simple--find your
      patient's goal threshold in under 5 minutes.

PMID- 19099035
TI  - We should stop paying for diagnostic failure and its downstream consequences.

PMID- 19099036
TI  - Endoscopic and surgical management of primary sclerosing cholangitis.
AB  - Primary sclerosing cholangitis (PSC) is a rare, chronic cholestatic liver disease
      of uncertain etiology characterized by the destruction of the intrahepatic and
      extrahepatic bile ducts through inflammation and fibrosis. This development of
      inflammation and fibrosis leads to biliary complications including cirrhosis and
      ultimately death. Given the uncertainty surrounding the pathogenesis of the
      disease, many different medical therapies have been studied in the treatment of
      PSC. However, there currently are no effective medical therapies known to halt
      progression of disease. Additionally, patients with PSC often develop symptoms
      and complications that can be managed endoscopically or surgically. This review
      primarily focuses on endoscopic and surgical approaches that have been studied in
      the treatment of patients with PSC.

PMID- 19099037
TI  - Palliation of a malignant rectal stricture and rectovesical fistula with colonic
      stenting.

PMID- 19099039
TI  - Beyond a dying private health insurance industry: a hidden solution in plain
      view.

PMID- 19099040
TI  - There's no place like the "medical home".

PMID- 19099041
TI  - Patient adherence to allergic rhinitis treatment: results from patient surveys.

PMID- 19099042
TI  - A 12-year-old boy with progressive dysphagia.

PMID- 19099044
TI  - Readers' and author's responses to "Electronic personal health records: should
      doctors worry?".

PMID- 19099045
TI  - What makes us humans unique? Here is a surprising answer: it's the sugar.

PMID- 19099046
TI  - Tissue-engineered blood vessels in pediatric cardiac surgery.
AB  - Pediatric cardiovascular surgeons often encounter patients requiring surgical
      intervention utilizing foreign materials to repair complex lesions. However, the
      materials that are commonly used lack growth potential, and long-term results
      have revealed several material-related failures, such as stenosis,
      thromboembolization, calcium deposition, and risk of infection. To solve these
      problems, in particular for children who require the implantation of dynamic
      material with growth potential, we sought to develop optimal filling materials
      with biocompatibility and growth potential. Previously, we reported the
      advantages of tissue-engineered vascular autografts (TEVAs) in animal models and
      in human clinical applications utilizing autologous cells and biodegradable
      scaffolds. The key benefits from utilizing such scaffolds is that they degrade in
      vivo, thereby avoiding the long-term presence of foreign ma-terials, and the
      seeded cells proliferate and differentiate to construct new tissue.Recent studies
      have demonstrated the existence of bone marrow-derived endothelial pro-genitor
      cells that contribute to vasculogenesis and angiogenesis and the successful
      endothelialization of artificial grafts using bone marrow cells. We provided
      evidence that bone marrow cells as a source for seeding onto a biodegradable
      scaffold are useful and that seeded cells contribute to the histogenesis of
      TEVAs. Therefore, we applied this technique in clinical trials with good results.
      In this review article, we provide an overview of our work developing "tissue
      engineered blood vessels" created by utilizing autologous mononuclear bone marrow
      cells.

PMID- 19099047
TI  - Solving the puzzle of chronic ischemic mitral regurgitation.
AB  - Chronic ischemic mitral regurgitation is a prevalent problem among patients
      following a myocardial infarction. Until recently, the pathophysiology was poorly
      understood, resulting in surgical strategies with suboptimal results and limited
      durability. The surgical approach has evolved from revascularization alone to an
      additional mitral valve procedure, replacement, or repair. When the valve was
      repaired, isolated annuloplasty was performed. The dilemma that surgeons had when
      repairing a mitral valve was which type of ring to use and what size. In all
      series with annuloplasty alone, the results were poor with very high recurrence
      rates. The primary feature of ischemic mitral regurgitation is a prolapse of the
      anterior leaflet at A3 +/- A2. This prolapse can be caused by fibrotic elongation
      of the papillary muscle supporting A3 +/- A2 or tethering of P3 by a ballooning
      posterior left ventricular wall. Using a technique that corrects this prolapse
      with Gore-Tex neochords, we have achieved excellent results with effective and
      durable correction of the ischemic mitral regurgitation.

PMID- 19099048
TI  - Thoracic aortic aneurysm: reading the enemy's playbook.
AB  - BACKGROUND: At the Yale University Center for Thoracic Aortic Disease, we have
      been using our clinical experience and laboratory investigations to shed light on
      the pathophysiology of thoracic aortic aneurysm (TAA), the clinical behavior of
      thoracic aortic aneurysm, and the optimal clinical management. MATERIALS AND
      METHODS: The Yale database contains information on 3,000 patients with thoracic
      aortic aneurysm, with 9,000 patient-years of follow-up and 9,000 imaging studies.
      Advanced statistical techniques were applied to this information. RESULTS:
      Analysis yielded the following Yale-generated observations: (1) TAA is a genetic
      disease with a predominantly autosomal dominant mode of inheritance; (2) matrix
      metalloproteinase (MMP) enzymes are activated in the pathogenesis of TAA; (3)
      wall tension in TAA approaches the tensile limits of aortic tissue at a diameter
      of 6 cm; (4) by the time a TAA reaches a clinical diameter of 6 cm, 34 percent of
      affected patients have suffered dissection or rupture; (5) extreme physical
      exertion or severe emotion often precipitate acute dissection; and (6) single
      nucleotide polymorphisms (SNPs) and RNA expression profile changes are being
      identified that predispose a patient to TAA and can serve as biomarkers for
      screening for this virulent disease. CONCLUSIONS: The "playbook" of TAA is
      gradually being read, with the help of scientific investigations, positioning
      practitioners to combat this lethal disease more effectively than ever before.

PMID- 19099049
TI  - Early specialization in surgery: the new frontier.

PMID- 19099050
TI  - Altar and table: a phenomenology of the surgeon-priest.

PMID- 19099051
TI  - Ambroise Pare and the birth of the gentle art of surgery.

PMID- 19099052
TI  - Women surgeons--still in a male-dominated world.

PMID- 19099053
TI  - Surgical instruments as a window into the profession's past.

PMID- 19099054
TI  - Molecular recognition, fluorescence sensing, and biological assay of phosphate
      anion derivatives using artificial Zn(II)-Dpa complexes.
AB  - In this Feature Article, we focus on recent advances in our research on molecular
      recognition and fluorescence sensing of phosphate anion derivatives of biological
      importance. Because of their significant roles in biological systems,
      considerable efforts have been devoted to developing detection or determination
      systems. However, the recognition and sensing of these anion species under
      aqueous biological conditions using small-molecular chemosensors still remain as
      a challenging research topic. We have been developing a variety of artificial
      receptors and fluorescent chemosensors for phosphoproteins and nucleoside
      polyphosphates in recent years. They consist of a binuclear Zn(II)-dipicolylamine
      (Dpa) complex as a common binding motif for phosphate anion derivatives. Taking
      advantage of their strong binding affinities or high sensing abilities, a variety
      of biological assay systems have also been successfully developed, which includes
      the enzyme assays such as the kinase, phosphatase and glycosyltransferase
      reaction, as well as an inhibitor assay for the phosphoprotein-protein surface
      interaction.

PMID- 19099055
TI  - Two-photon materials with large two-photon cross sections. Structure-property
      relationship.
AB  - The development of two-photon materials has been growing very fast during the
      last decade due to the potential applications in optical limiting, 3D
      microfabrication, and multiphoton microscopy. In this article, the structure-two
      photon absorption property relationships of dipolar, quadrupolar, and octupolar
      molecules as well as the derivatives of triphenylamine, [2.2]paracyclophanes,
      multi-annulenes, and porphyrins are briefly reviewed to provide a guideline for
      the design of efficient two-photon materials.

PMID- 19099056
TI  - A glimpse of the inner workings of the templated site.
AB  - This is the first direct experimental probe, using EXAFS, of the active site
      within molecularly imprinted polymers and paves the way to a more detailed
      understanding of the inner workings of molecular imprinting.

PMID- 19099057
TI  - Reversible proton coupled electron transfer in a peptide-incorporated
      naphthoquinone amino acid.
AB  - The synthesis of a naphthoquinone amino acid and its electrochemical
      characterization in a peptide is presented.

PMID- 19099058
TI  - Molecular encapsulation of a discrete (H2O)32 cluster with S6 symmetry in an
      organic crystalline supermolecule.
AB  - A discrete S6-symmetrical (H2O)32 cluster was encapsulated in the cavity of an
      organic co-crystalline supermolecule constructed by the co-crystallization of
      guanidinium and benzenetribenzoate ions through hydrogen bonds, pi-pi and cation
      pi interactions.

PMID- 19099059
TI  - Tunable light emission using quantum dot-coated upconverters.
AB  - Near infrared (NIR) upconverters only emit at a single visible wavelength;
      coating them with quantum dot multilayers allows the emission wavelength to be
      tuned across the visible spectrum.

PMID- 19099060
TI  - Sculpting the beta-peptide foldamer H12 helix via a designed side-chain shape.
AB  - The long-range side-chain repulsion between the (1R,2R,3R,5R)-2-amino-6,6
      dimethyl-bicyclo[3.1.1]-heptane-3-carboxylic acid (trans-ABHC) residues stabilize
      the H12 helix in beta-peptide oligomers.

PMID- 19099061
TI  - Twisted perylene dyes enable highly fluorescent and photostable nanoparticles.
AB  - Polymeric fluorescent nanoparticles with covalently embedded perylene
      fluorophores were developed by facile synthesis strategy and their advanced
      features of extremely high fluorescence intensity, non-photoblinking and
      excellent photostability were experimentally confirmed at the single nanoparticle
      level.

PMID- 19099062
TI  - A new quinoline sensitizer-centered lanthanide chelate and its use for protein
      labling on Ni-NTA beads for TR LRET assays.
AB  - A quinoline sensitizer-centered lanthanide chelate system of novel design for TR
      LRET was prepared; it exhibited high labelling efficiency with a his-tagged
      protein (ERalpha-LBD) on the Ni-NTA beads, using a mixed metal chelate protocol,
      and it functioned well in TR-LRET protein-protein interaction assays.

PMID- 19099063
TI  - A natural abundance 33S solid-state NMR study of layered transition metal
      disulfides at ultrahigh magnetic field.
AB  - Using a series of layered transition metal disulfides we demonstrate that the
      wide-line natural abundance solid-state NMR spectra of 33S in a less symmetric
      environment can readily be obtained at ultrahigh magnetic field of 21.1 T and
      that surprisingly these closely related materials display a wide range of 33S
      quadrupole coupling constant and chemical shift anisotropy values.

PMID- 19099064
TI  - Beta-vinyl substituted calix[4]pyrrole as a selective ratiometric sensor for
      cyanide anion.
AB  - A new calix[4]pyrrole-based, dual functional, chemodosimetric sensor was
      developed and studied as a cyanide selective indicator; complete color bleaching
      was observed even in the co-presence of an excess of other anions.

PMID- 19099066
TI  - Porous platinum nanowire arrays for direct ethanol fuel cell applications.
AB  - Porous Pt nanowire arrays show enhanced electrocatalytic activities for ethanol
      oxidation in direct alcohol fuel cells.

PMID- 19099065
TI  - Electrostatic determinants of stability in parallel 3-stranded coiled coils.
AB  - The optimal positioning of salt-bridging interactions in a parallel alpha-helical
      homotrimeric coiled coil has been explored in a metal ion-assembled polypeptide
      trimer of 60 residues; arginine-glutamate pairs are more stabilizing than the
      corresponding lysine-glutamate pairs, and optimal stabilization is obtained with
      positively charged arginine residues at the c positions of the alpha-helical
      heptad and negatively charged glutamate residues at the e positions.

PMID- 19099067
TI  - Reductive disproportionation of carbon dioxide to carbonate and squarate products
      using a mixed-sandwich U(III) complex.
AB  - The mixed-sandwich U(III) complexes [U(eta-C8H6{SiiPr(3)-1,4}2)(eta-CpR)(THF)]
      (R=Me5, Me4H) react with CO2 to give free CO and the U(IV) carbonate products
      [U(eta-C8H6{SiiPr(3)-1,4}2)(eta-CpR)]2(micro-eta1:eta2-CO3)]; the latter has been
      structurally characterised for R=Me4H; a 25% molar excess of the U(III) reductant
      gives a mixture of the carbonate and squarate [U(eta-C8H6{SiiPr(3)-1,4}2)(eta
      C5Me4H)]2(micro-eta2:eta2-C4O4) products-the first synthesis of an oxocarbon from
      a CO2 carbon source.

PMID- 19099068
TI  - 1-phosphabarrelene complexes of palladium and their use in Suzuki-Miyaura
      coupling reactions.
AB  - A bulky 1-phosphabarrelene, , was obtained from the reaction of a phosphinine
      with benzyne; two palladium complexes of were successfully employed in the Suzuki
      Miyaura coupling of several aryl chlorides with phenylboronic acid at a
      relatively low catalyst loading, and activated aryl chlorides were coupled at
      room temperature in the absence of strong bases.

PMID- 19099069
TI  - A new type of iodosulfite ion formulated as I2SO2(2-).
AB  - This paper deals with a notable halosulfite ion, (I2SO2(2-)), which is a rare
      example of this inorganic anion species; the reaction of the platinum(II)
      complex, [Pt(depe)2]I2 with SO2 afforded the complex, [Pt(depe)2](I2SO2)
      containing the rare anion; considering with the VSEPR concept, the structure of
      the anion could be interpreted as a distorted trigonal bipyramid.

PMID- 19099071
TI  - Supramolecular gel formation and self-correction induced by aggregation-driven
      conformational changes.
AB  - The formation of self-assembled fibrillar networks by low molecular weight
      peptidomimetics containing a Pro-Val moiety is reported; insight into the
      aggregation mechanism is provided revealing that it is associated to an unfolding
      process and that a fibrillar network formed under kinetic control can self
      correct into a thermodynamically stable one.

PMID- 19099070
TI  - Absolute helicity induction in three-dimensional homochiral frameworks.
AB  - Three Co(II) isomers assembled from D-, or L-, or DL-camphorate together with
      achiral isonicotinate exhibit a clear relationship between chirality and helicity
      even though chiral molecules are not in the backbone of the helix: the absolute
      sense of helix made of achiral components is controlled by chains of metal and
      enantiopure chiral ligands running perpendicular to helix in two enantiomeric
      forms.

PMID- 19099072
TI  - High surface area amorphous microporous poly(aryleneethynylene) networks using
      tetrahedral carbon- and silicon-centred monomers.
AB  - Poly(aryleneethynylene) networks prepared from tetrahedral monomers are highly
      microporous and exhibit apparent Brunauer-Emmett-Teller surface areas of up to
      1213 m2 g(-1).

PMID- 19099073
TI  - Oxygenation of alkylzinc complexes with pyrrolylketiminate ligand: access to
      alkylperoxide versus oxo-encapsulated complexes.
AB  - By variation of the zinc bonded alkyl group significantly different post
      oxygenation products, the novel zinc alkylperoxide and the tetranuclear zinc oxo
      encapsulated cluster, were derived from the controlled oxygenation of the
      corresponding alkylzinc complexes with a pyrrolylketiminate ligand.

PMID- 19099074
TI  - Template-free synthesis of Li[Ni0.25Li0.15Mn0.6]O2 nanowires for high performance
      lithium battery cathode.
AB  - Li[Ni0.25Li0.15Mn0.6]O2 nanowires having an aspect ratio of several hundreds and
      with a diameter of about 30 nm were synthesized at a pH of 2 during a
      hydrothermal process at 200 degrees C for 5 h without using a template. The
      nanowires exhibited a first discharge capacity of 311 mA h g(-1) and a rate
      capability of 95% at 4C (=1200 mA g(-1)).

PMID- 19099075
TI  - Asymmetric spin crossover behaviour and evidence of light-induced excited spin
      state trapping in a dinuclear iron(II) helicate.
AB  - Reported herein are the synthesis, structural and magnetic characterisation of a
      dinuclear FeII triple helicate that displays an unprecedented reversible
      asymmetric high spin to low spin crossover characterised by a thermal hysteresis:
      indeed the high spin state can be recovered by white light irradiation at 10 K.

PMID- 19099076
TI  - New strategy for targeting of photosensitizers. Synthesis of glycodendrimeric
      phenylporphyrins, incorporation into a liposome membrane and interaction with a
      specific lectin.
AB  - Two glycodendrimeric phenylporphyrins were synthesized and their interaction with
      phospholipids was studied at the air-water interface and in liposome bilayers;
      such liposomes bearing glycodendrimeric porphyrin could constitute an efficient
      carrier for drug targeting in photodynamic therapy.

PMID- 19099077
TI  - Observation of a dynamic equilibrium between DNA hairpin and duplex forms of
      covalent adducts of a minor groove binding agent.
AB  - A dynamic equilibrium between covalent 1:1 hairpin and 2:1 duplex DNA adducts of
      a pyrrolobenzodiazepine (PBD) minor groove binding agent () has been observed for
      the first time. The equilibrium, which establishes over 1 hour and must require
      unfolding of both types of adducts, is surprising given that PBDs normally
      require DNA minor groove structure for binding and take 24 hours for complete
      reaction with duplex DNA. The equilibrium is interesting from an energetics
      perspective due to the well known DNA stabilizing effect of PBDs. This
      observation could have significance for the in vitro and in vivo biological
      activity of PBDs, as DNA hairpin and loop structures are known to be important in
      cellular processes such as transcription and replication.

PMID- 19099078
TI  - Analysis of heme-reconstitution of apoenzymes by means of surface plasmon
      resonance.
AB  - Surface plasmon resonance was used to determine the kinetic parameters for heme
      reconstitution of apoenzymes.

PMID- 19099079
TI  - Stereoselective macrocyclization through zirconocene-mediated coupling of achiral
      dialkynes.
AB  - 1,4-Bis[trimethylsilyl(ethynyl)]naphthalene () and 1,4
      bis[trimethylsilyl(ethynyl)]anthracene () undergo diastereoselective coupling
      with Cp2Zr(py)(Me3SiC[triple bond, length as m-dash]CSiMe3) to give trimeric
      macrocycles in good yield.

PMID- 19099080
TI  - Ru(II)-carbohydrate dendrimers as photoinduced electron transfer lectin
      biosensors.
AB  - Three tris(bipyridine)ruthenium dendrimers bearing either six or eighteen mannose
      units have been synthesized; encapsulation of the Ru(bipy)3 core alters the rate
      of energy and electron transfer as well as the lectin biosensing abilities.

PMID- 19099081
TI  - Enzyme-catalyzed synthesis of isosteric phosphono-analogues of sugar nucleotides.
AB  - Efficient enzymatic syntheses of isosteric phosphono analogues of sugar
      nucleotides have been accomplished using a thymidylyltransferase.

PMID- 19099082
TI  - Visible light-induced photocatalytic reaction of gold-modified titanium(IV) oxide
      particles: action spectrum analysis.
AB  - Action spectrum analyses showed that visible light-induced oxidation of 2
      propanol by aerated gold-modified titanium(IV) oxide (titania) suspensions is
      initiated by excitation of gold surface plasmon, and polychromatic irradiation
      experiments revealed that the photocatalytic reaction rate depends strongly on
      properties of titania, such as particle size, surface area and crystalline form
      (anatase or rutile) and on properties of gold deposits, such as size and shape.

PMID- 19099083
TI  - Alkyl dehydrogenation in a Rh(I) complex via an isolated agostic intermediate.
AB  - A well-characterised 14-electron rhodium phosphine complex, [Rh(PiPr3)3][BArF4],
      which contains a beta-CH agostic interaction, is observed to undergo spontaneous
      dehydrogenation to afford [Rh(PiPr3)2(PiPr2(C3H5))][BArF4]; calculations on a
      model system show that while C-H activation is equally accessible from the beta
      CH agostic species or an alternative gamma-CH agostic isomer, subsequent beta-H
      transfer can only be achieved along pathways originating from the beta-CH agostic
      form.

PMID- 19099084
TI  - The role of surrogate endpoints in the evaluation of efficacy and safety of
      therapeutic interventions in diabetes mellitus.
AB  - In this paper, we examine the concept of surrogate endpoints (i.e. substitute
      outcome measures) and review their use in clinical trials involving therapies for
      diabetes mellitus using the example of metformin. Trials such as DCCT and UKPDS,
      in which patient-important endpoints were evaluated, are relatively rare in
      diabetology. Clinical decisions, therefore, are often based on evidence obtained
      using surrogate outcomes, usually fasting or postprandial glycemia or glycated
      hemoglobin level. In contrast to patient-important endpoints, surrogates do not
      describe direct clinical benefit to the patient. However, a proven association
      between a surrogate and patient-important endpoint is essential to draw
      appropriate therapeutic conclusions. In the process of new drug development, the
      duration of follow-up, sample size and methodology of the studies initially
      available are often inadequate to demonstrate the effect of the intervention on
      patient-important endpoints. Evidence concerning the effect of an intervention on
      surrogate outcomes usually comes first, followed only later by reports describing
      its influence on patient-important endpoints. Metformin may serve as an example
      in several ways. The first publications reported beneficial effects on glycemic
      control and body weight. Outcomes from the subsequent UKPDS study suggested the
      patient-important efficacy of metformin measured as a reduction in mortality and
      a decrease in the incidence of diabetic complications, including myocardial
      infarction. This reasoning process worked for some but not all strategies. It is
      particularly questionable whether a change in surrogate endpoint was associated
      with a potential deterioration in patient-important outcomes. Defining the
      general relationship between surrogates widely used as measures of metabolic
      control and patient-important endpoints remains an important challenge in
      contemporary diabetology.

PMID- 19099085
TI  - The current status of islet transplantation and its perspectives.
AB  - Transplantation of human pancreatic isolated islets can restore beta-cell
      function but it requires chronic immunosuppression. The outcome of islet
      transplantation mainly depends on both the quality of islet preparations, and the
      survival of the graft. The quality of islet preparations can be evaluated by the
      results of isolation, which determines the chance to achieve insulin
      independence. The survival of islet grafts is reflected by the amount of
      engrafted functional tissue that maintains metabolic control. Immunosuppressive
      therapy prevents the immunological rejection of grafts, but impairs their
      function and impedes their regenerative capacity. Therefore, the selection of
      high quality islet preparations and the reduction of toxic effects of
      immunosuppressive regimens might dramatically improve the outcomes. The
      application of stem cell therapy in islet transplantation may contribute to a
      better understanding of the mechanisms responsible for tissue homeostasis and
      immune tolerance. Xenogeneic islets may serve as an unlimited source if immune
      tolerance can be achieved. This may be a strategy to enable a substantial
      improvement in function while overcoming potentially deleterious risks.

PMID- 19099086
TI  - Incomplete Killing And Enhanced Activation of Islet-Reactive CD8+ T Cells by FasL
      Expressing Dendritic Cells Limits Protection from Diabetes.
AB  - AIMS: Autologous dendritic cells (DC) are a promising tool for induction of
      cytotoxic CD8+ T cell immunity against tumors and chronic viral infections. When
      armed with the death-inducing Fas-ligand (FasL, CD195), DC attenuate delayed-type
      hypersensitivity reactions and allotransplant rejection by promoting activation
      induced cell death in T cells. We investigated the possibility of using FasL
      expressing DC to induce deletion of islet-reactive CD8+ T cells in vivo, and to
      prevent destruction of pancreatic islets in a model of autoimmune diabetes.
      METHODS: DC, propagated from mouse bone marrow cells, were purified and made to
      express FasL and islet-antigen via plasmid transfection. CD8+ T cells (OT-I
      cells) recognizing the antigen, ovalbumin, were adoptively transferred to
      transgenic mice expressing ovalbumin in islets (RIP-OVA(lo) mice), and these mice
      were primed with ovalbumin. To test the potential of DC to prevent diabetes in
      this model, the mice were later intravenously vaccinated with the transfected DC.
      RESULTS: Transfected DC induced partial deletion of antigen-reactive CD8+ T cells
      in vivo and reduced the level of lymphocyte infiltration into pancreatic islets.
      Diabetes developed less frequently in vaccinated mice, but this effect was
      limited. Further in vitro analysis showed that FasL-expressing DC not only
      deleted many of the responding CD8+ T cells but also promoted the expansion of
      surviving cells and their IFN-gamma production. CONCLUSIONS: FasL-expressing DC
      can also have stimulatory effects on CD8+ T cells warranting further
      investigation into the optimal design of tolerance-promoting DC-vaccination to
      prevent autoimmune diabetes.

PMID- 19099087
TI  - Initiating or switching to biphasic insulin aspart 30/70 therapy in subjects with
      type 2 diabetes mellitus. An observational study.
AB  - OBJECTIVE: To investigate tolerability and glycemic control over 26 weeks in
      patients with type 2 diabetes (T2D) who initiated insulin with, or switched to,
      biphasic insulin aspart 30/70 (BIAsp 30) in routine clinical care. METHODS: This
      was a non-randomized, non-interventional, open-label, observational study
      involving patients under the care of approximately 150 insulin-prescribing
      physicians in Denmark. All patients enrolled were prescribed BIAsp 30 in routine
      care. Starting dose, dose titration and injection frequency were determined
      individually by each physician. Information on serious adverse drug reactions
      (SADR), glycemic parameters and hypoglycemic events were obtained from patients'
      notes, patients' diaries and recall, and transferred to case report forms by
      physicians at baseline (during 4 weeks prior to BIAsp 30 therapy) and after 12
      and 26 weeks of treatment. RESULTS: 421 subjects were recruited and 392 provided
      safety data. The age (mean +/- SD) was 62.0 +/- 11.4 years, body mass index (BMI)
      30.4 +/- 6.4 kg/m(2), duration of diabetes 9.1 +/- 8.1 years and HbA1c (%) 9.4 +/
      1.7. 199 subjects were prior insulin users and 193 were insulin-naive patients.
      Four patients reported a SADR (3 hypoglycemia, 1 severe hypoglycemia). HbA1c was
      significantly reduced after 26 weeks of BIAsp 30 therapy: prior insulin users 
      1.2%, insulin-naive patients -2.2% (both p < 0.001). 28% and 41% of patients,
      respectively, reached target HbA1c < 7%. Overall the hypoglycemia rate was lower
      for insulin-naive patients than for prior insulin users: 5.0 vs. 6.6
      episodes/patient-year (p < 0.05). CONCLUSION: Initiating insulin with, or
      switching insulin to, BIAsp 30 in routine care was safe and effective in patients
      with T2D.

PMID- 19099088
TI  - Effects of gender and height on the oral glucose tolerance test: the isfahan
      diabetes prevention study.
AB  - BACKGROUND: Impaired fasting glucose (IFG) is more prevalent in men, whereas
      impaired glucose tolerance (IGT) is more prevalent in women. AIM: To determine
      whether gender difference in the prevalence of glucose intolerance is related to
      height. METHODS: A cross-sectional study of 2,368 first-degree relatives (FDR) of
      patients with type 2 diabetes was conducted between years 2003 to 2005. All
      participants (614 men and 1754 women) were in the age range 30-60 years, and were
      FDR of consecutive patients from outpatient clinics at Isfahan Endocrine and
      Metabolism Research Centre, Iran. All subjects underwent a standard 75 g 2-h oral
      glucose tolerance test (OGTT). Weight, height, waist and hip circumference, and
      glycated haemoglobin were also measured. RESULTS: IGT was more common amongst
      women (OR 0.66; 95% CI 0.51, 0.87),whereas diabetes (OR 1.31; 95% CI 0.96, 1.78),
      and IFG (OR 1.41; 95% CI 1.10, 1.80) was more common amongst men. Women had a
      lower mean fasting plasma glucose (FPG) (p < 0.001), but showed higher 2hPG, and
      FPG-2hPG increase (p < 0.001). The gender difference in mean 2hPG and FPG-2hPG
      increase, was not evident after adjustment for height. Negative correlation to
      height was observed in 2hPG and FPG-2hPG increase, both in men and women (p <
      0.001), but height showed little association with FPG. CONCLUSIONS: Women had
      higher mean 2hPG and FPG-2hPG increase, but showed a lower FPG level than men.
      The inverse association between height and 2hPG and FPG-2hPG increase may be
      explained by gender difference.

PMID- 19099089
TI  - Tracing the Pathogenesis of Type 1 Diabetes: A Report on the 44th Annual Meeting
      of the European Association for the Study of Diabetes (EASD).
AB  - Clinical type 1 diabetes is preceded by autoimmune destruction of the pancreatic
      beta-cells. However, progression to disease is not uniform. One challenge facing
      current diabetes research is therefore to identify biomarker profiles that
      accurately reflect the individual stage of type 1 diabetes pathogenesis and
      develop new techniques to distinguish between these profiles and associated
      diabetes risks. This report highlights some of the recent studies on diabetes
      biomarkers, with a particular focus on zinc transporter ZnT8, presented at the
      EASD meeting in September 2008 in Rome, Italy.

PMID- 19099090
TI  - All we need is GWAS: Genome-Wide Association Studies in Type 2 Diabetes Mellitus
      presented on the 2008 EASD Meeting in Rome.
AB  - Several lines of evidence suggest that genetic susceptibility plays a major role
      in the pathogenesis of type 2 diabetes mellitus (T2DM). Limited success of
      candidate gene approach and linkage analysis in identifying the genetic
      background of T2DM has caused many research groups to apply the genome-wide
      association studies (GWAS) approach. Recently, several GWAS have identified and
      validated novel gene variants highly associated with T2DM. Unfortunately, most of
      the genetic variance in risk of T2DM still remains undiscovered. The main topic
      for discussion concerning genetics of T2DM during the 2008 EASD sessions was how
      to get more data from existing GWAS, and how to improve GWAS for the future. The
      presentations and subsequent discussions highlighted some clear weaknesses of
      GWAS that need to be overcome before further progress can be made. One recognized
      minefield is the inability to pick up the signals from true diabetes
      susceptibility variants, against the background statistical noise produced by a
      large number of other analyzed markers. Also, there are the problems of low
      sensitivity in identifying the signals from relatively rare variants, and the low
      effectiveness in identifying epistatic gene-gene interactions.

PMID- 19099091
TI  - Intensive Glycemic Control and Macrovascular Disease in Type 2 Diabetes - A
      Report on the 44th Annual EASD Meeting, Rome, Italy, September 2008.
AB  - The impact of strict glycemic control on the prevention of macrovascular diseases
      in type 2 diabetes patients has remained unresolved for decades. New results
      presented at the EASD meeting shed new light on this question. Recent data from
      the United Kingdom Prospective Diabetes Study (UKPDS) showed that intensive
      glycemic control, when initiated immediately after diagnosis of type 2 diabetes
      and continued for a period of ten years followed by another ten years without
      special intervention, prevents myocardial infarction and decreases all-cause
      mortality. The Veterans Affairs Diabetes Trial demonstrated that striving to
      achieve near-normal glycemia in older patients with relatively long duration of
      diabetes and, in many cases, previous macrovascular events did not reduce future
      macrovascular events but increased the risk of severe hypoglycemia. These results
      indicate that effective treatment of hyperglycemia should be started early after
      diabetes diagnosis. However, introducing strict diabetes control after more than
      10 years diabetes duration may lead to unfavorable effects in patients with
      hitherto unsatisfactorily controlled diabetes.

PMID- 19099092
TI  - Anti-diabetic Agents in Type 2 Diabetes: A Review of New Data Presented and
      Discussed on the EASD meeting in Rome, 2008.
AB  - The results of a number of large trials and the arrival of new glucose-lowering
      drugs are changing the scene of diabetes care in patients with type 2 diabetes.
      The results of the ADVANCE and ACCORD trials have shown that strict glycemic
      control does not improve macrovascular outcome. Consequently, the importance of
      duration of disease, presence of cardiovascular disease and risk of hypoglycemia,
      have been brought again into focus as considerations in designing individual
      treatment plans.. New drugs related to the incretin system have emerged in the
      past year, and these may decrease certain risks of classic glucose-lowering
      drugs. However, we have to be aware of the possibility of yet unknown longer-term
      risks from newly developed drugs. The new insights from the trials presented on
      the EASD meeting 2008 and the emerging information on the new drugs are used in
      this paper to start defining the contours of prospective new treatment
      strategies.

PMID- 19099093
TI  - Induced sputum cell counts in medical practice.

PMID- 19099094
TI  - Influence of a DNA-hsp65 vaccine on bleomycin-induced lung injury.
AB  - OBJECTIVE: To evaluate the effects of immunization with a DNA-hsp65 vaccine in an
      experimental model of pulmonary fibrosis. METHODS: A total of 120 male C57BL/6
      mice were distributed into four groups: SS, injected with saline (placebo) and
      then receiving intratracheal (IT) instillation of saline; SB, injected with
      saline (placebo) and then receiving IT instillation of bleomycin; PB, treated
      with plasmid only, without bacterial genome, and then receiving IT instillation
      of bleomycin; and BB, treated with the vaccine and then receiving IT instillation
      of bleomycin. Bleomycin was instilled 15 days after the last immunization, and
      the animals were killed six weeks thereafter. The left and right lungs were
      removed, the former for morphological analysis and the latter for hydroxyproline
      measurements. RESULTS: The proportion of deaths within the first 48 h after the
      IT instillation (deaths attributed to the surgical procedure) was higher in the
      SB group than in the SS group (57.7% vs. 11.1%). The mean area of pulmonary
      interstitial septa was greater in the SB and PB groups (53.1 +/- 8.6% and 53.6+/
      9.3%, respectively) than in the SS and BB groups (32.9 +/- 2.7% and 34.3 +/-
      6.1%, respectively). The mean area of interstitial septa stained by picrosirius
      was greater in the SB, PB and BB groups than in the SS group (8.2 +/- 4.9%, 7.2
      +/- 4.2% and 6.6 +/- 4.1%, respectively, vs. 2.0+/-1.4%). The total
      hydroxyproline content in the lung was significantly lower in the SS group (104.9
      +/- 20.9 pg/lung) than in the other groups (SB: 160.4 +/- 47.8 pg/lung; PB: 170.0
      +/- 72.0 pg/lung; and BB: 162.5 +/- 39.7 pg/lung). CONCLUSIONS: Immunization with
      the DNA-hsp65 vaccine reduced the deposition of noncollagen matrix in a model of
      bleomycin-induced lung lesion.

PMID- 19099095
TI  - Prevalence of allergic bronchopulmonary aspergillosis in patients with cystic
      fibrosis in the state of Bahia, Brazil.
AB  - OBJECTIVE: To determine the prevalence of allergic bronchopulmonary aspergillosis
      (ABPA) in patients with cystic fibrosis treated at a referral center in the state
      of Bahia, Brazil. METHODS: A cross-sectional study, with prospective data
      collection, carried out at the Cystic Fibrosis Referral Center of Bahia of the
      Octavio Mangabeira Specialized Hospital. We evaluated 74 patients diagnosed with
      cystic fibrosis, older than six years of age, treated between December 9, 2003
      and March 7, 2005. We analyzed the following variables: gender, age, forced vital
      capacity, forced expiratory volume in one second, pharmacodynamic response, chest
      X-ray findings, facial sinus X-ray findings, wheezing, cultures for Aspergillus
      spp., total immunoglobulin E (IgE), specific IgE for Aspergillus fumigatus and
      immediate skin test reactivity to A.fumigatus antigen. RESULTS: Of the 74
      patients, 2 were diagnosed with ABPA. We found total IgE levels > 1,000 IU/mL in
      17 (23%), positive immediate skin reactivity to A. fumigatus antigen in 19
      (25.7%) and wheezing in 60 (81.1%). CONCLUSIONS: The prevalence of ABPA was 2.7%.
      The high levels of total IgE, high incidence of wheezing and high rate of
      immediate skin test reactivity to A. fumigatus antigen suggest that these
      patients should be carefully monitored due to their propensity to develop ABPA.

PMID- 19099096
TI  - Pulmonary function and respiratory muscle strength in chronic renal failure
      patients on hemodialysis.
AB  - OBJECTIVE: To evaluate pulmonary function and respiratory muscle strength in
      chronic renal failure patients, correlating these variables with hemodialysis
      related weight fluctuation; to study the correlation between the duration
      hemodialysis and potential respiratory alterations. METHODS: Seventeen patients
      (median age, 47 years; interquartile range, 41-52 years), submitted to three
      weekly hemodialysis sessions for a median of 27 months (interquartile range, 14
      55) were evaluated. Twelve of the patients were male. The patients underwent
      spirometry. Maximal inspiratory pressure (MIP) and maximal expiratory pressure
      (MEP) were measured prior to and after the first hemodialysis session of the
      week. Body weight was quantified prior to and after each of the three weekly
      sessions. RESULTS: Before the first hemodialysis session of the week, 8 patients
      presented mild restrictive defect, which normalized after the session in 2 of
      those patients. After dialysis, there was a significant increase in forced vital
      capacity (p = 0.02) and a significant decrease in body weight (p = 0.0001).
      Weight fluctuation over 3 days without hemodialysis tended to correlate with the
      variation in forced vital capacity in the first weekly session (r = 0.47; p =
      0.055). Duration of hemodialysis correlated with predialysis MIP (r = -0.3; p =
      0.03) and MEP (r = -0.63; p = 0.006). CONCLUSIONS: More pronounced weight gain in
      the interdialytic period is associated with worsening of lung function, which is
      almost fully reversible by hemodialysis. In addition, longer duration of
      hemodialysis is associated with decreased respiratory muscle strength.

PMID- 19099097
TI  - Determination of the inflammatory component of airway diseases by induced sputum
      cell counts: use in clinical practice.
AB  - OBJECTIVE: To evaluate the usefulness of determining the inflammatory component
      of airway diseases (inflammometry) by induced sputum cell counts, as well as its
      influence on treatment decisions in a tertiary facility for the treatment of
      respiratory diseases. METHODS: We analyzed 151 sputum samples from 132
      consecutive patients referred for clinical sputum induction by five
      pulmonologists between July of 2006 and February of 2007. A structured
      questionnaire related to the reasons for requesting the test and to the
      therapeutic decision making based on test results was completed by each attending
      physician upon receiving the test results. Induced sputum was obtained and
      processed according to a technique previously described. RESULTS: The principal
      motives for ordering the test were inhaled corticosteroid dose titration in
      patients with moderate-to-severe asthma (in 54.3%), investigation of chronic
      cough (in 30.5%), and monitoring airway inflammation in patients with
      bronchiectasis (in 7.3%) or chronic obstructive pulmonary disease (in 6%). Of the
      82 patients with asthma, 47 (57%) presented eosinophilic bronchitis (>3%
      eosinophils). Nonasthmatic eosinophilic bronchitis was diagnosed in 9 (19%) of
      the 46 patients with chronic cough. Neutrophilic bronchitis (>65% neutrophils)
      was found in 13 patients, of which 5 had asthma, 2 had chronic cough, and 6 had
      chronic obstructive pulmonary disease/bronchiectasis. Based on the induced sputum
      results, the corticosteroid dose was modified in 48 asthma patients (64.7%).
      CONCLUSIONS: The systematic application of inflammometry using induced sputum
      cell counts can be beneficial for patients with airway diseases, particularly
      those with asthma or chronic cough.

PMID- 19099098
TI  - Gene probes versus classical methods in the identification of mycobacteria.
AB  - OBJECTIVE: The emergence of tuberculosis/HIV co-infection and the increase in the
      number of cases of infection with nontuberculous mycobacteria (NTM) require rapid
      laboratory test results in the isolation and identification of mycobacteria. The
      objective of this study was to evaluate the identification of mycobacteria by
      means of gene probes in comparison with that obtained using classical biochemical
      methods. METHODS: Between 2002 and 2004, 178 mycobacterial cultures, all testing
      positive for acid-fast bacilli, were analyzed. Samples were obtained from
      clinical specimens of patients with respiratory symptoms or with clinical
      suspicion of pulmonary tuberculosis/mycobacteriosis who were treated in the
      greater metropolitan area of Santos. RESULTS: The gene probe identified 137
      samples (77%) as Mycobacterium tuberculosis complex and 41 (23%) as NTM.
      Discordant results between the methods (3%) were obtained only in the year of
      implementation (2002). When comparing the methods, the sensitivity, specificity,
      positive predictive value and negative predictive value of the gene probe method
      were 98%, 93%, 98% and 93%, respectively. CONCLUSIONS: Despite the cost, the
      identification of mycobacteria using the molecular technique is faster: maximum 3
      h vs. 28-30 days for classical methods. The use of gene probes is a validated
      molecular technique. It is fast, easy to use and readily available on the market.
      It has high specificity and sensitivity, which justifies its implementation and
      routine use in referral laboratories, since it facilitates the diagnosis
      providing agile clinical interventions.

PMID- 19099099
TI  - Factors associated with cigarette experimentation among adolescents.
AB  - OBJECTIVE: To assess the prevalence of and factors associated with smoking
      experimentation among adolescents. METHODS: Cross-sectional study, using a
      specific questionnaire to interview 2,883 students from 7th to 10th grade in
      schools located in the urban area of the city of Cuiaba, in the state of Mato
      Grosso, Brazil. Prevalence was estimated, and the principal factors related to
      cigarette experimentation were analyzed. Subsequently, a hierarchical logistic
      model was used to describe the chances of cigarette experimentation related to
      the variables being investigated. RESULTS: The prevalence of cigarette
      experimentation was 30.2%. In the final model of the analysis, the main variables
      related to cigarette experimentation were low maternal level of education (OR =
      2.44; 95% CI: 1.72-3.47); low socioeconomic level (OR=1.39; 95% CI: 1.01-1.93);
      studying in a public school (OR = 1.56; 95% CI: 1.22-2.00); being in 10th grade
      (OR = 3.45; 95% CI: 2.63-4.54); attending school in the evening (OR = 2.44; 95%
      CI: 1.85-3.22); having divorced parents (OR = 1.23; 95% CI: 1.02-1.49); having
      been held back for one school year (OR = 2.17; 95% CI: 1.78-2.70); having friends
      who smoke (OR = 3.75; 95% CI: 2.99-4.70) having a sibling who smokes (OR = 2.44;
      95% CI: 1.82-3.27); and being older (age 17-19 years) (OR = 2.44; 95% CI: 1.39
      4.17). CONCLUSIONS: A high proportion of adolescents have experimented with
      smoking. After adjusting for confounding variables, the factors most strongly
      associated with cigarette experimentation were maternal level of education, age
      of the adolescent, attending school in the evening, having been held back for one
      school year and having a sibling who smokes. Preventive measures must be directed
      at adolescents in schools in order to control smoking.

PMID- 19099100
TI  - Smoking among hospitalized patients in a general hospital.
AB  - OBJECTIVE: To determine the frequency of smoking among hospitalized patients in a
      general hospital, and to evaluate their profile. METHODS: A random representative
      sample of 111 patients, classified as nonsmokers, former smokers or smokers, was
      evaluated. The smokers were submitted to the Fagerstrom test and measurement of
      expired carbon monoxide. Expired carbon monoxide higher than 6 ppm was considered
      a significant indicator of recent smoking. RESULTS: Of the 111 patients in the
      sample, 60 (54%) were female. The mean age was 70 years. Of the 111 patients, 56
      (51%) had never smoked, 36 (32%) were former smokers, and 19 (17%) were smokers.
      All of the smokers were male. The smokers were younger (58 +/- 17 years) than the
      nonsmokers (68 +/- 14 years) and the former smokers (73 +/- 14 years)--ANOVA: F =
      6.57 (p = 0.002). Among the smokers, the mean tobacco intake was 43 pack-years
      and the mean Fagerstrom score was 5.0. Of the 19 smokers, 11 (58%) had
      respiratory symptoms and 3 had withdrawal symptoms. The mean expired carbon
      monoxide in the smokers was 5.0 ppm. Expired carbon monoxide levels were higher
      than 6 ppm in 8 (42%) of the smokers. There was a higher prevalence of smokers in
      some wards: 70% of all smokers were hospitalized on only five wards. CONCLUSIONS:
      In a large tertiary hospital, 17% of the hospitalized patients were smokers, and
      7% had smoked within the last 8 hours. The smokers were younger men, hospitalized
      on specific wards.

PMID- 19099101
TI  - Cytokines and acute phase serum proteins as markers of inflammatory regression
      during the treatment of pulmonary tuberculosis.
AB  - OBJECTIVE: To evaluate the pattern of pro-inflammatory cytokines, anti
      inflammatory cytokines and the acute phase response (APR) as markers of the
      response to treatment of pulmonary tuberculosis. METHODS: Twenty-eight patients
      with pulmonary tuberculosis were evaluated at three time points: pretreatment
      (T0), treatment month 3 (T3) and treatment month 6 (T6). Levels of interferon
      gamma (IFN-gamma), tumor necrosis factor-alpha (TNF-alpha), interleukine-10 (IL
      10) and transforming growth factor-beta (TGF-beta) were determined using ELISA in
      the supernatant of peripheral blood mononuclear cell and monocyte culture. Levels
      of total protein, albumin, globulins, C-reactive protein (CRP), alpha-1-acid
      glycoprotein (AAG) and erythrocyte sedimentation rate (ESR) were also determined.
      All of these parameters were also evaluated, only once, in a group of healthy
      controls. RESULTS: In relation to controls, patients presented cytokine levels
      and APR that were higher at T0, lower at T3 and either lower (TNF-alpha, IL-10,
      TGF-beta, AAG and ESR) or normal (IFN-gamma and CRP) at T6. CONCLUSIONS: For
      individuals with negative smear sputum microscopy, CRP, AAG and ESR are potential
      markers of pulmonary tuberculosis and of the need for treatment; CRP (T0 > T3 >
      T6 = reference) can also be a marker of treatment response. In the patients, the
      Th0 profile (IFN-gamma, IL-10, TNF-alpha and TGF-beta), inducer of and protector
      against inflammation, predominated at T0, whereas the Th2 profile (IL-10, TNF
      alpha and TGF-beta), protecting against the harmful pro-inflammatory effect of
      the remaining TNF-alpha, predominated at T6. The behavior of IFN-gamma (T0 > T3 >
      T6 = controls) suggests its use as a marker of treatment response.

PMID- 19099102
TI  - Nontuberculous mycobacteria isolated in Sao Jose do Rio Preto, Brazil between
      1996 and 2005.
AB  - OBJECTIVE: To study the incidence of nontuberculous mycobacteria and the range of
      species isolated between 1996 and 2005 at a regional branch of the Adolfo Lutz
      Institute-located in the city of Sao Jose do Rio Preto, Brazil-and to show the
      importance of laboratory testing. METHODS: Mycobacteria were isolated from
      pulmonary and extrapulmonary specimens and identified through phenotyping and
      molecular methods (polymerase chain reaction-restriction enzyme analysis).
      RESULTS: We isolated 317 nontuberculous mycobacterium strains: Mycobacterium
      avium complex, 182 (57.4%); M. gordonae, 33 (10.4%); M. fortuitum, 25 (7.9%); M.
      chelonae, 8 (2.5%); M. terrae complex, 8(2.5%); M.kansasii, 7 (2.2%); and less
      frequent species, 54 (17%). During this period, 72 cases (33.3%) were
      characterized as mycobacteriosis, according to bacteriological criteria
      established by the American Thoracic Society in 2007. Of those 72 cases, 56 were
      attributed to M.avium complex. Of those 56, 29 (51.8%) were characterized as
      disseminated disease. Six cases were attributed to M. fortuitum, 3 to M.
      gordonae, 2 to M. chelonae, 1 to M. abscessus, 1 to M. kansasii, 1 to M.
      intracellulare, 1 to M. malmoense and 1 to Mycobacterium ssp. CONCLUSIONS: These
      results show the importance of the bacteriological diagnosis, since
      identification of the species enables early and appropriate treatment.

PMID- 19099103
TI  - Bronchoscopy for foreign body removal: where is the delay?
AB  - This was a retrospective analysis of the medical charts of 145 patients treated
      at the Bronchoscopy and Thoracic Surgery Clinic of the Hospital das Clinicas da
      Universidade Estadual de Campinas (HC-Unicamp, State University of Campinas
      Hospital das Clinicas) over a period of 10 years. There was a significant
      difference related to the site of first medical visit (Unicamp-HC versus other
      institutions) in terms of the time elapsed between the suspicion of bronchial
      aspiration and the actual respiratory endoscopic examination. However, no
      significant difference was found in the rate of positive results. The low number
      of referral centers that provide emergency respiratory endoscopy can negatively
      influence the treatment of patients under suspicion of bronchial aspiration,
      jeopardizing the overall recovery in the mid- and long-term.

PMID- 19099104
TI  - Tuberculosis and silicosis: epidemiology, diagnosis and chemoprophylaxis.
AB  - Silicosis, the most prevalent of the pneumoconioses, is caused by inhalation of
      crystalline silica particles. Silica-exposed workers, with or without silicosis,
      are at increased risk for tuberculosis and nontuberculous mycobacteria-related
      diseases. The risk of a patient with silicosis developing tuberculosis is higher
      (2.8 to 39 times higher, depending on the severity of the silicosis) than that
      found for healthy controls. Various regimens for tuberculosis chemoprophylaxis in
      patients with silicosis have been studied, all of which present similar efficacy
      and overall risk reduction to about one half of that obtained with placebo. Long
      term regimens have potential side effects (particularly hepatotoxicity). In
      addition, the use of such regimens can jeopardize adherence to treatment. The
      current guidelines recommend that tuberculin skin tests be performed, and, if
      positive, that chemoprophylaxis be instituted. There are several possible
      regimens, varying in terms of the drugs prescribed, as well as in terms of
      treatment duration. We recommend the use of isoniazid at 300 mg/day (or 10
      mg/kg/day) for six months for patients with silicosis, as well as for healthy
      patients with periods of exposure to silica longer than 10 years and strongly
      positive tuberculin skin test results (induration > or = 10 mm). Nevertheless,
      further studies are necessary so that indications, drugs, doses and duration of
      chemoprophylaxis regimens can be more properly defined.

PMID- 19099105
TI  - Guidelines for the prevention, diagnosis and treatment of compensatory
      hyperhidrosis.
AB  - With the objective of establishing guidelines for the prevention, diagnosis and
      treatment of compensatory hyperhidrosis, consensus meetings were held. Attendees
      included a general surgeon and thoracic surgeons affiliated with the Brazilian
      Society of Thoracic Surgery. The topics addressed were those that would
      ostensibly broaden multidisciplinary knowledge. Based on recent guidelines for
      the prevention, diagnosis and (clinical and surgical) treatment of compensatory
      hyperhidrosis, as well as on a review of the medical literature, the participants
      prepared a preliminary text, whose recommendations were revised and subsequently
      approved by all of the participants. The consensus text was posted on the
      Internet, becoming the object of further corrections and revisions prior to
      taking on its present form.

PMID- 19099106
TI  - Gynecomastia: a rare adverse effect of isoniazid.
AB  - We report the case of a patient who twice developed gynecomastia following
      tuberculosis treatment. An 18-year-old male developed painful bilateral
      gynecomastia after three months of treatment with the isoniazid-rifampin
      pyrazinamide regimen. Partial resolution of gynecomastia was achieved at the end
      of treatment. The patient was retreated with the same regimen eight years later,
      and gynecomastia recurred after six months of treatment. Hormone levels were
      normal, and a mammogram revealed bilateral gynecomastia. The isoniazid was
      discontinued, and the gynecomastia was partially resolved by the end of
      treatment. Four years later, gynecomastia was not detected. We conclude that
      isoniazid-related gynecomastia completely resolves when the medication is
      discontinued. Therefore, pharmacological and surgical treatment should be
      avoided.

PMID- 19099107
TI  - Cystic lymphangioma of the mediastinum.
AB  - Cystic lymphangioma is a rare congenital benign tumor. It results from focal
      proliferation of well-differentiated lymphatic tissue originating from abnormal
      development of the lymphatic system. Most cystic lymphangiomas occur in the
      primitive lymph sacs of children or young adults. They generally appear in the
      neck (75%) and axillary region (20%). Only 1% are located in the mediastinum.
      Acquired lymphangiomas, which are principally seen in middle-aged adults, are
      caused by a process of chronic lymphatic obstruction secondary to surgery,
      chronic infection, or radiation. Here, we present the case of a 50-year-old male
      with cystic lymphangioma of the mediastinum, detected on a routine chest X-ray.

PMID- 19099108
TI  - Pulmonary nocardiosis in a patient with chronic obstructive pulmonary disease and
      bronchiectasis.
AB  - We report the case of a patient with chronic obstructive pulmonary disease and
      bronchiectasis, chronically using corticosteroids, who acquired pulmonary
      nocardiosis, which presented as multiple cavitated nodules. The principal
      symptoms were fever, dyspnea and productive cough with purulent sputum. Chest X
      ray and computed tomography of the chest revealed nodules, some of which were
      cavitated, in both lungs. Sputum smear microscopy and culture revealed the
      presence of Nocardia spp. The patient was treated with imipenem and cilastatin,
      which produced an excellent clinical response.

PMID- 19099109
TI  - The use of animals in experimental studies.

PMID- 19099111
TI  - Transcranial Doppler for patent foramen ovale screening: is there a good
      correlation with transesophageal echocardiography?
AB  - Right-to-left shunt (RLS) can be identified by contrast-enhanced transcranial
      Doppler (cTCD) in patent foramen ovale (PFO) patients. AIM: To evaluate cTCD for
      PFO screening comparing it to cTEE. METHOD: 45 previous cTCD performed for PFO
      diagnosis and correlated its findings with cTEE. Patients were submitted to a
      cTCD standardized technique and were divided in two groups according to RLS:
      Group 1, patients with a positive RLS and Group 2 when RLS was negative. RESULTS:
      29 (65%) patients were included in group 1 and 16 (35%) in group 2. PFO
      confirmation by cTEE was performed in 28 (62%) patients. cTCD had a 92.85%
      sensitivity, 82.35% specificity, 89.65% positive predictive value and 87.5%
      negative predictive value when compared to cTEE for PFO diagnosis. CONCLUSION:
      Standardized technique cTCD allows for RLS visualization in PFO patients with a
      good correlation with cTEE and can be used as a screening test before cTEE.

PMID- 19099112
TI  - Endovascular treatment for intracranial infectious aneurysms.
AB  - OBJECTIVE: To re-enforce an alternative, less aggressive treatment modality in
      the management of intracranial infectious aneurysms. METHOD: We present a series
      of five patients with infectious endocarditis and intracranial infectious
      aneurysms (mycotic aneurysms) managed by means of endovascular treatment.
      RESULTS: Endovascular treatment was executed technically uneventfully in all
      patients. Three patients had favorable clinical outcome: two were classified as
      Glasgow Outcome Scale 4/5, and one had total neurological recovery (GOS 5/5). Two
      patients died (GOS 1/5), one in consequence of the initial intracranial bleeding
      and the other after cardiac complications from endocarditis and open-heart
      surgery. CONCLUSION: Endovascular techniques are an expanding option for the
      treatment of IIAs. It has been especially useful for infectious endocarditis
      patients with IIA, who will be submitted to cardiac surgery with cardiopulmonary
      bypass and anticoagulation, with the risk of intracranial bleeding.

PMID- 19099113
TI  - Familial cerebral cavernous malformations: Rio de Janeiro study and review of the
      recommendations for management.
AB  - OBJECTIVE: Multiple cerebral cavernous malformation (CCM) is the hallmark of
      familial presentation of cavernous malformation in the brain. We describe an
      ongoing Familial Cerebral Cavernous Malformation Project in the Rio de Janeiro
      state showing genetic profile and the pattern of emergent neuroimaging findings
      of this particular population besides a review of the updated recommendations for
      management of familial CCM versus patients harboring sporadic lesions. METHOD:
      Four families of our cohort of 9 families were genetically mapped showing
      mutational profile linked to CCM1. The neuroimaging paradigm was shifted from
      T2*gradient-echo (GRE) sequence to susceptibility weighting MR phase imaging
      (SWI). RESULTS: Only two index cases were subjected to surgery. There was no
      surgical intervention in any of the kindreds of our entire cohort of 9 families
      of our Neurovascular Program within seven years of follow-up. The genetic
      sequencing for mutational profile in four of these families has demonstrated only
      CCM1 gene affected. Our management of the familial CCM is according to the review
      of the literature recommendations. CONCLUSIONS: The Project of Familial Cerebral
      Cavernous Malformations of Rio de Janeiro detected mutations of the gene CCM1 in
      the first four families studied. Familial cavernous malformation are to be
      settled apart from the more common sporadic lesion. A set of recommendations was
      searched for in the literature in order to deal with these specific patients and
      kindreds.

PMID- 19099114
TI  - Clinical features of dystonia in atypical parkinsonism.
AB  - BACKGROUND: The association between Dystonia and Parkinson's disease (PD) has
      been well described especially for foot and hand dystonia. There is however few
      data on dystonic postures in patients with atypical parkinsonism. OBJECTIVE: To
      evaluate the frequency and pattern of dystonia in a group of patients with
      atypical parkinsonism (multiple system atrophy - MSA, progressive supranuclear
      palsy - PSP, and corticobasal degeneration - CBD) and to investigate whether
      dystonia could be the first presenting symptom at disease onset in those
      patients. METHOD: A total of 38 medical charts were reviewed (n=23/MSA group;
      n=7/CBD group; n=8/PSP group) and data values were described as means/standard
      deviations. The variables evaluated were sex, age at onset, disease duration,
      first symptom, clinical features of dystonia and other neurological signs,
      response to levodopatherapy, Hoehn &Yahr -scale >3 after three years of disease,
      and magnetic resonance imaging findings. RESULTS: The overall frequency of
      dystonia in our sample was 50% with 30.4% (n=7) in the MSA group, 62.5% (n=5) in
      the PSP group, and 100% (n=8) in the CBD group. In none of these patients,
      dystonia was the first complaint. Several types of dystonia were found:
      camptocormia, retrocollis, anterocollis, blepharoespasm, oromandibular, and
      foot/hand dystonia. CONCLUSION: In our series, dystonia was a common feature in
      atypical parkinsonism (overall frequency of 50%) and it was part of the natural
      history although not the first symptom at disease onset. Neuroimaging
      abnormalities are not necessarily related to focal dystonia, and levodopa therapy
      did not influence the pattern of dystonia in our group of patients.

PMID- 19099115
TI  - Head tremor in patients with cervical dystonia: different outcome?
AB  - OBJECTIVE: The association of cervical dystonia (CD) with other movement
      disorders have been already described, but data on clinical outcome regarding
      these patients are scant. The aim of this paper was to investigate whether
      patients with CD and head tremor (HT) would have a different outcome regarding to
      botulinum toxin type-A (BTX-A) treatment response and clinical and demographic
      parameters. METHOD: We retrospectively evaluated 118 medical charts of patients
      with CD and divided them into two groups: with (HT+) and without (HT-) head
      tremor. We compared the following clinical and demographic parameters: age at
      onset, disease duration, progression of symptoms, etiology, familial history,
      presence of hand tremor. We also analyzed the response to BTX-A according to Tsui
      score in both groups. RESULTS: The occurrence of head tremor in our sample was of
      38.2%. The occurrence of postural hand tremor in the patients from the HT+ group
      was higher than in the HT- one (p=0.015) and if we compare BTX-A response in each
      group, we observe that patients with HT present a better outcome in a setting of
      longer follow-up. In HT+ group, Tsui score pre treatment was 10 (6-12.5) and
      after follow-up was 8 (5.5-10.5); p<0.001. In HT- group there was no significant
      difference 9 (7-12) in pre treatment and after follow-up; p=0.07. CONCLUSION:
      According to our data it seems that head tremor may influence the clinical
      outcome or treatment response with BTX-A in patients with CD.

PMID- 19099116
TI  - Impact of cognitive performance on the functional capacity of an elderly
      population in Natal, Brazil.
AB  - Functional incapacity and cognitive impairment are conditions related to the
      process of human aging. Cognitive impairment is considered an important
      predicitve factor for functional impairment in elderly populations. This cross
      sectional study analyzes the association between cognitive performance and
      functional capacity in an elderly population sample in Natal, Brazil. A total of
      213 elderly persons were assessed by the BOAS Multidimensional Questionnaire
      (Brazil Old Age Schedule) and the Mini-Mental State Examination (MMSE). The
      results of multivariate analysis and linear regression showed that age and
      schooling level are factors associated with cognitive performance in the elderly
      of this study. The final explicative model, elaborated by logistic regression,
      found that cognitive performance was the only predicitve variable of functional
      incapacity for the activities of daily living even when adjusted for
      sociodemographic variables.

PMID- 19099117
TI  - Quality of life and sleep impairment in chronic cocaine dependents.
AB  - OBJECTIVE: To evaluate quality of life (QL) and sleep quality impairment of
      cocaine chronic dependents in use of cocaine. METHOD: 40 patients, chronic
      cocaine dependents were evaluated (37 M; 3 F), with mean age of 28.92 years,
      along with 40 controls paired for gender and age. The following instruments were
      used: a) the semi-structured clinical interview; b) the Brazil Economic
      Classification; c) the Pittsburgh Sleep Quality Index; d) World Heath
      Organization Quality of Life-BREF (WHOQOL-BREF). RESULTS: The cocaine dependents
      showed QL impairment, with deficits in the physical, psychological and social
      relations domains. Impaired sleep quality was also observed in the cocaine
      dependents. However, the QL impairment was not directly due to sleep deficit.
      CONCLUSION: Chronic cocaine dependents showed impairment in QL and sleep
      impairment. However, for the cocaine dependent group, sleep impairment was not
      regarded as compromising QL probably because cocaine, rather than sleep, was the
      main factor negatively influencing QL.

PMID- 19099118
TI  - Women living with HIV/AIDS: sleep impairment, anxiety and depression symptoms.
AB  - OBJECTIVE: To evaluate sleep impairment, symptoms of anxiety and depression, and
      associations with sleep characteristics of sleep in female HIV/AIDS patients.
      METHOD: 30 female patients with HIV/AIDS were evaluated along with 30 female
      controls with a mean age of 35.4 years in the study group and 33.1 years in the
      control group, with: a) the Pittsburgh Sleep Quality Index; b) the Beck Anxiety
      Inventory; c) the Beck Depression Inventory. RESULTS: Sleep quality was more
      impaired in AIDS patients than in those with HIV+ or in controls. The AIDS
      patients showed more symptoms of anxiety. There were associations of sleep
      impairment with anxiety in HIV+ patients; whereas in AIDS patients associations
      were found between sleep impairment and depression. CONCLUSION: There was sleep
      quality in the presence of symptoms of anxiety and depression. In HIV+ patients,
      sleep impairment was associated with anxiety, while in AIDS patients sleep
      impairment was associated with depression.

PMID- 19099119
TI  - Clinical and neuropsychological profile in a sample of children with attention
      deficit hyperactivity disorders.
AB  - The aim of this study was to evaluate clinical and neuropsychological findings in
      children with suspicion of attention deficity hyperactivity disorder (ADHD). The
      assessment involved 150 children aged 7 to 14 referred to NANI at UNIFESP.
      RESULTS: 75 children (55 M and 20 F) fulfilled the criteria for ADHD, among which
      35 were of the inattentive type, 28 of combined type and 12 were
      hyperactive/impulsive. There was negative correlation between the digit score and
      the Corsi test. Children with hyperactivity and impulsivity had a low performance
      for functional memory. Children with oppositional defiant disorder presented
      pattern changes in adaptability when there was a change in the rhythm the stimuli
      were presented and lower adaptation to time variability (Hit RT), in addition to
      higher rates of omission in the continuous performance test. CONCLUSION: This
      study suggests multiple interrelations between the scores of neuropsychological
      battery useful for detailed delimitation of the clinical profile of children with
      ADHD.

PMID- 19099120
TI  - Inattention, hyperactivity, oppositional-defiant symptoms and school failure.
AB  - BACKGROUND: Attention-deficit hyperactivity disorder (ADHD) is associated with
      school failure. Inattention has been mainly implicated for this association.
      Oppositional-defiant disorder's (ODD) impact on academic performance remains
      controversial, because of the high comorbidity between ODD and ADHD. OBJECTIVE:
      To understand the role of inattention (IN), hyperactivity (H/I) and ODD in school
      failure. METHOD: Parents and teachers filled out SNAP-IV questionnaires for 241 /
      6th grade students. The associations of the scores of oppositional-defiant (OP),
      H/I and IN symptoms with school year failure were calculated. RESULTS: IN was
      strongly correlated with school failure. H/I and OP were not associated with
      school failure, when controlled for IN. CONCLUSION: OP and H/I symptoms do not
      play an important role in school failure, when controlled for IN symptoms. Our
      study supports the cross-cultural role of IN as a major predictor of school
      failure.

PMID- 19099121
TI  - Translation and validation into the Brazilian Portuguese of the restless legs
      syndrome rating scale of the International Restless Legs Syndrome Study Group.
AB  - BACKGROUND: Restless legs syndrome (RLS) is a chronic sensory-motor disorder
      characterized by unpleasant limb sensations and an irresistible urge to move. The
      International Restless Legs Syndrome Study Group developed the Restless Legs
      Syndrome Rating Scale (IRLS) to assess the severity of RLS symptoms. The
      objective of this study was to translate and validate the IRLS into Brazilian
      Portuguese. METHOD: The IRLS was translated into Brazilian Portuguese, analyzed,
      back translated to English, and compared to the original version. It was applied
      to 10 patients for cultural verification. The language was adjusted and the final
      version was administered to 30 patients (13 male, mean age 58.88+/-14.82).
      RESULTS: There was correlation among the IRLS evaluation of three experts. Many
      linguistic adaptations were required to achieve cultural adequacy and the
      Cronbach's alpha coefficient showed reliability of 80%. CONCLUSION: IRLS was
      translated, adapted, and validated to Brazilian Portuguese language, showing good
      reliability and validity.

PMID- 19099122
TI  - Influence of NMDA and non-NMDA antagonists on acute and inflammatory pain in the
      trigeminal territory: a placebo control study.
AB  - NMDA and non-NMDA receptors are involved in spinal transmission of nociceptive
      information in physiological and pathological conditions. Our objective was to
      study the influence of NMDA and non-NMDA receptor antagonists on pain control in
      the trigeminal system using a formalin-induced orofacial pain model. Motor
      performance was also evaluated. Male Rattus norvegicus were pre-treated with
      topiramate (T) (n=8), memantine (M) (n=8), divalproex (D) (n=8) or isotonic
      saline solution (ISS) (n=10) intraperitoneally 30 minutes before the formalin
      test. Formalin 2.5% was injected into the right upper lip (V2 branch) and induced
      two phases: phase I (early or neurogenic) (0-3 min) and phase II (late or
      inflammatory) (12-30 min). For motor behavior performance we used the open-field
      test and measured latency to movement onset, locomotion and rearing frequencies,
      and immobility time. Pre-treatment of animals with M and D only attenuated
      nociceptive formalin behavior for phase II. T increased locomotion and rearing
      frequencies and reduced immobility time. Treatment with M increased immobility
      time and with D reduced locomotion frequency. Our results showed that the NMDA
      antagonist (M) is more potent than the non-NMDA antagonists (D and T) in the
      control of pain in the inflammatory phase. The non-NMDA topiramate improved motor
      performance more than did D and M, probably because T has more anxiolytic
      properties.

PMID- 19099123
TI  - Neonatal administration of fluoxetine did not alter the anxiety indicators, but
      decreased the locomotor activity in adult rats in the elevated plus-maze.
AB  - The objective of this study was evaluate the anxiety and locomotor activity (LA)
      in 52 Wistar adult male rats, being 26 treated with fluoxetine (10 mg/Kg - sc) in
      the neonatal period. These same rats received foot shock (FS) (1.6-mA - 2-s) in
      the 90th day. The anxiety and LA were appraised by plus-maze. The time spent in
      the open arms was used as anxiety index and the LA was measured by number of
      entries in closed arms (NECA) and the total of entries (TE). T-test was used with
      p<0.05 and expresses data in mean+/-SEM. There were reductions with the
      fluoxetine group in the NECA (2.35+/-0.33) and in the TE (3.96+/-0.61) compared
      to the controls (4.65+/-0.52) and (6.96+/-0.94). The neonatal administration of
      fluoxetine did not alter the anxiety, but reduced the LA in the animals that
      received FS.

PMID- 19099124
TI  - Is cold the new hot in sudden unexpected death in epilepsy? Effect of low
      temperature on heart rate of rats with epilepsy.
AB  - Sudden unexpected death in epilepsy (SUDEP) is the commonest cause of seizure
      related mortality in people with refractory epilepsy. Several risk factors for
      SUDEP are described; however, the importance of including low temperatures as
      risk factor for SUDEP was never explored. Based on this, the aim of this study
      was to evaluate the heart rate of rats with epilepsy during low temperature
      exposure. Our results showed that low temperature clearly increased the heart
      rate of rats with epilepsy. Taken together, we concluded that exposure to low
      temperatures could be considered important risk factors from cardiovascular
      abnormalities and hence sudden cardiac death in epilepsy.

PMID- 19099125
TI  - Neurogenesis induced by seizures in the dentate gyrus is not related to mossy
      fiber sprouting but is age dependent in developing rats.
AB  - Neurogenesis in the dentate gyrus (DG) has attracted attention since abnormal
      supragranular mossy fiber sprouting occurs in the same region, in temporal lobe
      epilepsy. Thus, we submitted developing rats to pilocarpine-induced status
      epilepticus (SE) to study the relationship between neurogenesis and mossy fiber
      sprouting. Groups were submitted to SE at: I-P9, II-P7, P8 and P9, III-P17 e IV
      P21. Neurogenesis was quantified using BrdU protocol and confirmed through double
      staining, using neuronal pentraxin. Other animals were monitored by video system
      until P120 and their brain was studied (Timm and Nissl staining). The
      neurogenesis at P17 (p=0.007) and P21 (p=0.006) were increased. However, only P21
      group showed recurrent seizures and the mossy fiber sprouting in the same region,
      during adult life, while P17 did not. Thus, our results suggest that neurogenesis
      is not related to mossy fiber sprouting neither to recurrent spontaneous seizures
      in pilocarpine model.

PMID- 19099126
TI  - A randomized clinical trial of oral steroids for ulnar neuropathy in type 1 and
      type 2 leprosy reactions.
AB  - BACKGROUND: Steroids regimens in leprosy neuropathies are still controversial in
      botth types of reactions. METHOD: For this trial, 21 patients with ulnar
      neuropathy were selected from 163 leprosy patients, 12 with type 1 reaction (T1R)
      and nine with type 2 (T2R). One experimental group started with prednisone 2
      mg/kg/day and the control group with 1 mg/kg/day. A clinical score based on tests
      for spontaneous pain, nerve palpation, sensory and muscle function was used.
      Neurophysiological evaluation consisted on the motor nerve conduction of the
      ulnar nerve in three segments. Student "t" test for statistical analysis was
      applied on the results: before treatment, first week, first month and sixth
      month, between each regimen and types of reaction. CONCLUSION: In both reactions
      during the first month higher doses of steroids produced better results but,
      earlier treatment with lower dose was as effective. Short periods of steroid, 1
      mg/Kg/day at the beginning and,tapering to 0,5 mg/Kg/day or less in one month
      turned out to be efficient in T2R.

PMID- 19099127
TI  - Relationship between the coronal suture and the central lobe: how important is it
      and how can we use it in surgical planning?
AB  - The surgical treatment of the lesions located in the central lobe is a very
      difficult task for the neurosurgeon. The overall aim of this study is to verify
      the correlation of the coronal suture and the structures of the central lobe in
      32 cadaver hemisphere brains and the importance of this information in surgical
      planning. The measurement of the nasion to the coronal suture ranged from 11.5 to
      13.5 cm. The distance between the coronal suture in the midline to the central,
      precentral and paracentral sulcus ranged from 5.0 to 6.6, 2.5 to 4.5 and 1.3 to
      4.0 cm respectively. Particularly in the normal cortex these measurements can be
      used to guide the surgical access. However, the identification of the central
      sulcus is not easy when the anatomical pattern is distorted or displaced by a
      lesion or edema. In cases such as these the use of other tools becomes crucial
      for good surgical planning and cortical mapping or awake craniotomy for a safer
      resection of the lesion as well.

PMID- 19099128
TI  - Microsurgical approach of arteriovenous malformations in the central lobule.
AB  - Arteriovenous malformations (AVM) are neurovascular disorders that occur mainly
      in young adults. Their clinical presentation is variable and depends on its
      location, size and occurrence of bleeding. They can represent incidental findings
      in neuro radiological exams. The treatment of these lesions when located in
      eloquent areas, namely around the central sulcus, is controversial, with
      different therapeutical approaches presented in the literature. We consider that
      surgical extirpation of many of these lesions is feasible in selected cases ,
      when supported by profound anatomical knowledge and refined microsurgical
      technique, achieving cure with minimal additional deficit. In the present
      article, we elaborate a surgical technique for the approach of AVMs located in
      the central sulcus, specially in finding the topographic lesion location and
      craniotomy.

PMID- 19099129
TI  - Microsurgical techniques using human placenta.

PMID- 19099130
TI  - Cerebellar glioblastoma multiforme in an adult.

PMID- 19099131
TI  - Tumour-like chagasic encephalitis in AIDS patients: an atypical presentation in
      one of them and outcome in a small series of cases.

PMID- 19099132
TI  - Rapid BOLD fMRI signal loss in the primary motor cortex of a stroke patient.

PMID- 19099133
TI  - An amyotrophic lateral sclerosis mimicker: eosinophilic fasciitis.

PMID- 19099134
TI  - Myotonic potentials in statin-induced rhabdomyolysis.

PMID- 19099135
TI  - Venlafaxine induced-myoclonus in a patient with mixed dementia.

PMID- 19099136
TI  - Pisa syndrome induced by rapid increase and high dosage of risperidone.

PMID- 19099137
TI  - Swallowing dysfunction in hereditary neuropathy with liability to pressure
      palsies.

PMID- 19099138
TI  - Trigemino autonomic cephalalgia and Argyll Robertson pupil.

PMID- 19099139
TI  - Hashimoto's encephalopathy with clinical features similar to those of Creutzfeldt
      Jakob disease.

PMID- 19099140
TI  - Multi-lacunar strokes mimicking atypical parkinsonism with an unusual
      neuroimaging presentation: etat crible.

PMID- 19099141
TI  - Bilateral amaurosis due to brain aneurysm rupture.

PMID- 19099142
TI  - Normal hearing after resection of a large vestibular schwannoma.

PMID- 19099143
TI  - Middle cranial fossa arachnoid cysts complicated with subdural collections.

PMID- 19099144
TI  - Anomalous branch of the right common carotid artery.

PMID- 19099145
TI  - Charcot's contribution to the study of Tourette's syndrome.
AB  - We review the history of Tourette syndrome, emphasizing the contribution of Jean
      Martin Charcot.

PMID- 19099146
TI  - Spontaneous cervical artery dissection: an update on clinical and diagnostic
      aspects.
AB  - Spontaneous cervical arterial dissection (SCAD) is a non-traumatic tear or
      disruption in the wall of the internal carotid arteries or the vertebral
      arteries. It accounts for about 25% of strokes in patients aged under 45 years.
      Awareness of its clinical features and advances in imaging over the last two
      decades have contributed to earlier identification of this condition. SCAD has
      become the commonest form of vascular lesion identified in the cervical carotid
      and vertebral arteries, second only to atherosclerosis. This review is an update
      on the epidemiology, vulnerable arterial segments, risk factors, clinical
      features, diagnosis, current treatment and prognosis of SCAD.

PMID- 19099148
TI  - Breathing pattern and thoracoabdominal motion during exercise in chronic
      obstructive pulmonary disease.
AB  - Subjects with chronic obstructive pulmonary disease (COPD) present breathing
      pattern and thoracoabdominal motion abnormalities that may contribute to exercise
      limitation. Twenty-two men with stable COPD (FEV1 = 42.6 +/- 13.5% predicted; age
      68 +/- 8 years; mean +/- SD) on usual medication and with at least 5 years of
      diagnosis were evaluated at rest and during an incremental cycle exercise test
      (10 watts/2 min). Changes in respiratory frequency, tidal volume, rib cage and
      abdominal motion contribution to tidal volume and the phase angle that measures
      the asynchrony were analyzed by inductive respiratory plethysmography at rest and
      during three levels of exercise (30-50, 70-80, and 100% maximal work load).
      Repeated measures ANOVA followed by pre-planned contrasts and Bonferroni
      corrections were used for analyses. As expected, the greater the exercise
      intensity the higher the tidal volume and respiratory frequency. Abdominal motion
      contributed to the tidal volume increase (rest: 49.82 +/- 11.19% vs exercise:
      64.15 +/- 9.7%, 63.41 +/- 10%, and 65.56 +/- 10.2%, respectively, P < 0.001) as
      well as the asynchrony [phase angle: 11.95 +/- 7.24 degrees at rest vs 22.2 +/-
      15 degrees (P = 0.002), 22.6 +/- 9 degrees (P < 0.001), and 22.7 +/- 8 degrees (P
      < 0.001), respectively, at the three levels of exercise]. In conclusion, the
      increase in ventilation during exercise in COPD patients was associated with the
      major motion of the abdominal compartment and with an increase in the asynchrony
      independent of exercise intensity. It suggests that cycling exercise is an
      effective way of enhancing ventilation in COPD patients.

PMID- 19099149
TI  - Reduced cortical renal GLUT1 expression induced by angiotensin-converting enzyme
      inhibition in diabetic spontaneously hypertensive rats.
AB  - Diabetes in spontaneously hypertensive rats is associated with cortical renal
      GLUT1 and GLUT2 overexpression. Our objective was to evaluate the effect of the
      angiotensin-converting enzyme blockade on cortical renal GLUT1 and GLUT2
      expression, urinary albumin and urinary TGF-beta1. Streptozotocin, 50 mg/kg, or
      citrate buffer (N = 16) was administered as a single injection into the tail vein
      in adult spontaneously hypertensive rats (approximately 260 g). Thirty days
      later, these diabetic spontaneously hypertensive rats received ramipril by
      gavage: 0.01 mg x kg(-1) x day(-1) (D0.01, N = 14), 1 mg x kg(-1) x day(-1) (D1,
      N = 9) or water (D, N = 11) for 15 days. Albumin and TGF-beta1 (24-h urine),
      direct arterial pressure, renal tissue angiotensin-converting enzyme activity
      (fluorometric assay), and GLUT1 and GLUT2 protein levels (Western blot, renal
      cortex) were determined. Glycemia and glycosuria were higher (P < 0.05) in the
      diabetic rats compared with controls, but similar between the diabetic groups.
      Diabetes in spontaneously hypertensive rats lowered renal tissue angiotensin
      converting enzyme activity (40%), which was reduced further when higher ramipril
      doses were used. Diabetes associated with hypertension raised GLUT1 by 28% (P <
      0.0001) and GLUT2 by 76% (P = 0.01), and both doses of ramipril equally reduced
      cortical GLUT1 (D vs D1 and vs D0.01, P < or = 0.001). GLUT2 levels were reduced
      in D0.01 (P < 0.05 vs D). Diabetes increased urinary albumin and TGF-beta1
      urinary excretion, but the 15-day ramipril treatment (with either dose) did not
      reduce them. In conclusion, ramipril is effective in lowering renal tissue
      angiotensin-converting enzyme activity, as well as blocking cortical GLUT1
      overexpression, which may be beneficial in arresting the development of diabetic
      nephropathy.

PMID- 19099150
TI  - Cloning, purification and comparative characterization of two digestive lysozymes
      from Musca domestica larvae.
AB  - cDNA coding for two digestive lysozymes (MdL1 and MdL2) of the Musca domestica
      housefly was cloned and sequenced. MdL2 is a novel minor lysozyme, whereas MdL1
      is the major lysozyme thus far purified from M. domestica midgut. MdL1 and MdL2
      were expressed as recombinant proteins in Pichia pastoris, purified and
      characterized. The lytic activities of MdL1 and MdL2 upon Micrococcus
      lysodeikticus have an acidic pH optimum (4.8) at low ionic strength (mu = 0.02),
      which shifts towards an even more acidic value, pH 3.8, at a high ionic strength
      (mu = 0.2). However, the pH optimum of their activities upon 4-methylumbelliferyl
      N-acetylchitotriozide (4.9) is not affected by ionic strength. These results
      suggest that the acidic pH optimum is an intrinsic property of MdL1 and MdL2,
      whereas pH optimum shifts are an effect of the ionic strength on the negatively
      charged bacterial wall. MdL2 affinity for bacterial cell wall is lower than that
      of MdL1. Differences in isoelectric point (pI) indicate that MdL2 (pI = 6.7) is
      less positively charged than MdL1 (pI = 7.7) at their pH optima, which suggests
      that electrostatic interactions might be involved in substrate binding. In
      agreement with that finding, MdL1 and MdL2 affinities for bacterial cell wall
      decrease as ionic strength increases.

PMID- 19099151
TI  - Potential pathogenic role of aggregative-adhering Corynebacterium diphtheriae of
      different clonal groups in endocarditis.
AB  - Invasive diseases caused by Corynebacterium diphtheriae have been described
      increasingly. Several reports indicate the destructive feature of endocarditis
      attributable to nontoxigenic strains. However, few reports have dealt with the
      pathogenicity of invasive strains. The present investigation demonstrates a
      phenotypic trait that may be used to identify potentially invasive strains. The
      study also draws attention to clinical and microbiological aspects observed in 5
      cases of endocarditis due to C. diphtheriae that occurred outside Europe. Four
      cases occurred in female school-age children (7-14 years) treated at different
      hospitals in Rio de Janeiro, Brazil. All patients developed other complications
      including septicemia, renal failure and/or arthritis. Surgical treatment was
      performed on 2 patients for valve replacement. Lethality was observed in 40% of
      the cases. Microorganisms isolated from 5 blood samples and identified as C.
      diphtheriae subsp mitis (N = 4) and C. diphtheriae subsp gravis (N = 1) displayed
      an aggregative adherence pattern to HEp-2 cells and identical one-dimensional SDS
      PAGE protein profiles. Aggregative-adhering invasive strains of C. diphtheriae
      showed 5 distinct RAPD profiles. Despite the clonal diversity, all 5 C.
      diphtheriae invasive isolates seemed to display special bacterial adhesive
      properties that may favor blood-barrier disruption and systemic dissemination of
      bacteria. In conclusion, blood isolates from patients with endocarditis exhibited
      a unique adhering pattern, suggesting a pathogenic role of aggregative-adhering
      C. diphtheriae of different clones in endocarditis. Accordingly, the aggregative
      adherence pattern may be used as an indication of some invasive potential of C.
      diphtheriae strains.

PMID- 19099152
TI  - An ultrasound and histomorphological analysis of experimental liver cirrhosis in
      rats.
AB  - We investigated whether liver injury by dual exposure to ethanol and carbon
      tetrachloride (EtOH + CCl4) for 15 weeks would persist after hepatotoxic agents
      were removed (EtOH + CCl4/8wR). After 15 weeks of hepatic injury with ethanol
      (5.5%, m/v) and carbon tetrachloride (0.05, mL/kg, ip), 5 of 11 female Wistar
      rats were sacrificed. The other 6 rats were maintained for an additional 8 weeks
      without hepatotoxic agents. Ultrasonography showed increased liver echogenicity
      and dilation of portal vein caliber in both groups (EtOH + CCl4: 0.22 +/- 0.01
      cm, P < 0.001; EtOH + CCl4/8wR: 0.21 +/- 0.02 cm, P < 0.01) vs control (0.16 +/-
      0.02 cm). Histopathology showed regenerative nodules in both experimental groups.
      Histomorphometry revealed increased fibrosis content in both groups (EtOH + CCl4:
      12.6 +/- 2.64%, P < 0.001; EtOH + CCl4/8wR: 10.4 +/- 1.36%, P < 0.05) vs control
      (2.2 +/- 1.21%). Collagen types I and III were increased in groups EtOH + CCl4
      (collagen I: 2.5 +/- 1.3%, P < 0.01; collagen III: 1.3 +/- 0.2%, P < 0.05) and
      EtOH + CCl4/8wR (collagen I: 1.8 +/- 0.06%, P < 0.05; collagen III: 1.5 +/- 0.8%,
      P < 0.01) vs control (collagen I: 0.38 +/- 0.11%; collagen III: 0.25 +/- 0.06%).
      Tissue transglutaminase increased in both groups (EtOH + CCl4: 66.4 +/- 8%, P <
      0.01; EtOH + CCl4/8wR: 58.8 +/- 21%, P < 0.01) vs control (7.9 +/- 0.8%).
      Cirrhosis caused by the association of CCl4-EtOH remained for at least 8 weeks
      after removal of these hepatotoxic agents. Ultrasound images can be a useful tool
      to evaluate advanced hepatic alterations.

PMID- 19099153
TI  - Long-term aerobic swimming training by rats reduces the number of aberrant crypt
      foci in 1,2-dimethylhydrazine-induced colon cancer.
AB  - We determined the effect of long-term aerobic swimming training regimens of
      different intensities on colonic carcinogenesis in rats. Male Wistar rats (11
      weeks old) were given 4 subcutaneous injections (40 mg/kg body weight each) of
      1,2-dimethyl-hydrazine (DMH, dissolved in 0.9% NaCl containing 1.5% EDTA, pH
      6.5), at 3-day intervals and divided into three exercise groups that swam with 0%
      body weight (EG1, N = 11), 2% body weight (EG2, N = 11), and 4% body weight of
      load (EG3, N = 10), 20 min/day, 5 days/week for 35 weeks, and one sedentary
      control group (CG, N = 10). At sacrifice, the colon was removed and counted for
      tumors and aberrant crypt foci. Tumor size was measured and intra-abdominal fat
      was weighed. The mean number of aberrant crypt foci was reduced only for EG2
      compared to CG (26.21 +/- 2.99 vs 36.40 +/- 1.53 crypts; P < 0.05). Tumor
      incidence was not significantly different among groups (CG: 90%; EG1: 72.7%; EG2:
      90%; EG3: 80%). Swimming training did not affect either tumor multiplicity (CG:
      2.30 +/- 0.58; EG1: 2.09 +/- 0.44; EG2: 1.27 +/- 0.19; EG3: 1.50 +/- 0.48 tumors)
      or size (CG: 1.78 +/- 0.24; EG1: 1.81 +/- 0.14; EG2: 1.55 +/- 0.21; EG3: 2.17 +/-
      0.22 cm(3)). Intra-abdominal fat was not significantly different among groups
      (CG: 10.54 +/- 2.73; EG1: 6.12 +/- 1.15; EG2: 7.85 +/- 1.24; EG3: 5.11 +/- 0.74
      g). Aerobic swimming training with 2% body weight of load protected against the
      DMH-induced preneoplastic colon lesions, but not against tumor development in the
      rat.

PMID- 19099154
TI  - Anti-cyclic citrullinated peptide antibodies and rheumatoid factor in leprosy
      patients with articular involvement.
AB  - The objective of the present research was to evaluate the usefulness of anti
      cyclic citrullinated peptide (anti-CCP) antibodies and the IgM rheumatoid factor
      (IgM RF) test for the differential diagnosis of leprosy with articular
      involvement and rheumatoid arthritis (RA). Anti-CCP antibodies and IgM RF were
      measured in the sera of 158 leprosy patients (76 with and 82 without articular
      involvement), 69 RA patients and 89 healthy controls. Leprosy diagnosis was
      performed according to Ridley and Jopling classification criteria and clinical
      and demographic characteristics of leprosy patients were collected by a standard
      questionnaire. Leprosy patients with any concomitant rheumatic disease were
      excluded. Serum samples were obtained from all participants and frozen at -20
      degrees C. Measurement of anti-CCP antibodies and IgM RF were performed by ELISA,
      using a commercial second-generation kit, and the latex agglutination test,
      respectively. Anti-CCP antibodies and IgM RF were detected in low frequencies
      (2.6 and 1.3%, respectively) in leprosy patients and were not associated with
      articular involvement. Among healthy individuals both anti-CCP antibodies and IgM
      RF were each detected in 3.4% of the subjects. In contrast, in the RA group, anti
      CCP antibodies were present in 81.2% and IgM RF in 62.3%. In the present study,
      both anti-CCP antibodies and IgM RF showed good positive predictive value for RA,
      helping to discriminate between RA and leprosy patients with articular
      involvement. However, anti-CCP antibodies were more specific for RA diagnosis in
      the population under study.

PMID- 19099155
TI  - Hyperthermia induced after recirculation triggers chronic neurodegeneration in
      the penumbra zone of focal ischemia in the rat brain.
AB  - Chronic neurodegenerative processes have been identified in the rat forebrain
      after prolonged survival following hyperthermia (HT) initiated a few hours after
      transient global ischemia. Since transient global ischemia and ischemic penumbra
      share pathophysiological similarities, this study addressed the effects of HT
      induced after recirculation of focal brain ischemia on infarct size during long
      survival times. Adult male Wistar rats underwent intra-luminal occlusion of the
      left middle cerebral artery for 60 min followed by HT (39.0-39.5 degrees C) or
      normothermia. Control procedures included none and sham surgery with and without
      HT, and middle cerebral artery occlusion alone. Part I: 6-h HT induced at
      recirculation. Part II: 2-h HT induced at 2-, 6-, or 24-h recirculation. Part
      III: 2-h HT initiated at recirculation or 6-h HT initiated at 2-, 6- or 24-h
      recirculation. Survival periods were 7 days, 2 or 6 months. The effects of post
      ischemic HT on cortex and striatum were evaluated histopathologically by
      measuring the area of remaining tissue in the infarcted hemisphere at -0.30 mm
      from bregma. Six-hour HT initiated from 6-h recirculation caused a significant
      decrease in the remaining cortical tissue between 7-day (N = 8) and 2-month (N =
      8) survivals (98.46 +/- 1.14 to 73.62 +/- 8.99%, respectively). When induced from
      24-h recirculation, 6-h HT caused a significant reduction of the remaining
      cortical tissue between 2- (N = 8) and 6-month (N = 9) survivals (94.97 +/- 5.02
      vs 63.26 +/- 11.97%, respectively). These data indicate that post-ischemic HT
      triggers chronic neurodegenerative processes in ischemic penumbra, suggesting
      that similar fever-triggered effects may annul the benefit of early recirculation
      in stroke patients over the long-term.

PMID- 19099156
TI  - Health technology assessments, evidence-based healthcare and health ethics.

PMID- 19099157
TI  - Predictors of quality of life among patients on dialysis in southern Brazil.
AB  - CONTEXT AND OBJECTIVE: Quality of life (QoL) is considered important as an
      outcome measurement, especially for long-term diseases such as chronic renal
      failure. The present study searched for predictors of QoL in a sample of patients
      undergoing dialysis in southern Brazil. DESIGN AND SETTING: This was a cross
      sectional study developed in three southern Brazilian dialysis facilities.
      METHODS: Health-related QoL of patients on hemodialysis or peritoneal dialysis
      was measured using the generic Short Form-36 (SF-36) health survey questionnaire.
      The results were correlated with sociodemographic, clinical and laboratory
      variables. The analysis was adjusted through multiple linear regression. RESULTS:
      A total of 140 patients were assessed: 94 on hemodialysis and 46 on peritoneal
      dialysis. The mean age was 54.2 +/- 15.4 years, 48% were men and 76% were white.
      The predictors of higher (better) physical component summary in SF-36 were:
      younger age (beta-0.16; 95% confidence interval, CI: -0.27 to -0.05), shorter
      time on dialysis (beta-0.06; 95% CI: -0.09 to -0.02) and lower Khan comorbidity
      age index (beta 5.16; 95% CI: 1.7-8.6). The predictors of higher mental component
      summary were: being employed (beta 8.4; 95% CI: 1.7-15.1), being married or
      having a marriage-like relationship (beta 4.56; 95% CI: 0.9-8.2), being on
      peritoneal dialysis (beta 4.9; 95% CI: 0.9-8.8) and not having high blood
      pressure (beta 3.9; 95% CI: 0.3-7.6). CONCLUSIONS: Age, comorbidity and length of
      time on dialysis were the main predictors of physical QoL, whereas socioeconomic
      issues especially determined mental QoL.

PMID- 19099158
TI  - The correlation between health status and quality of life in southern Brazil.
AB  - CONTEXT AND OBJECTIVE: The interconnections between quality of life and health
      status as assessed via questionnaires have not been thoroughly investigated. The
      objective of this study was to investigate a possible correlation between the
      constructs of general health status and quality of life as assessed by the
      Portuguese versions of two questionnaires recently adapted and tested in Brazil.
      DESIGN AND SETTING: This was a cross-sectional study in which two self
      administered questionnaires were used. This investigation was conducted at
      healthcare services associated with the Universidade de Caxias do Sul, Brazil.
      METHODS: This study presents data from a sample of 120 volunteers who completed
      the Portuguese versions of the Personal Health Scale and the Multicultural
      Quality of Life Index questionnaires. Bivariate linear regression analysis and
      Pearson correlation coefficients were generated from the scores of the two
      questionnaires. RESULTS: A significant correlation between the concepts of
      quality of life and health status as evaluated by the Portuguese versions of both
      questionnaires was observed. Almost all of the health-related questions displayed
      strong correlations with the overall concept of quality of life. The magnitude of
      this correlation accounted for almost half of the observed variance. CONCLUSIONS:
      These findings indicate that, within this sample, health-related issues were key
      factors for the overall experience of wellbeing and quality of life. The
      similarities observed across the different groups indicate that the interrelation
      between health status and quality of life was homogenous, regardless of presence
      and/or type of ailments.

PMID- 19099159
TI  - The expression of vulnerability through infant mortality in the municipality of
      Embu.
AB  - CONTEXT AND OBJECTIVE: Infant mortality expresses a set of living, working and
      healthcare access conditions and opens up possibilities for adopting
      interventions to expand equity in healthcare. This study aimed to investigate
      vulnerability and the consequent differences in access to health services and
      occurrences of deaths among infants under one year of age in the municipality of
      Embu. DESIGN AND SETTING: This was a descriptive study in the municipality of
      Embu. METHODS: Primary data were collected through interviews with the families
      of children living in the municipality of Embu who died in the years 1996 and
      1997 before reaching one year of age. Secondary data were obtained from death
      certificates. The variables collected related to living conditions, income,
      occupation, prenatal care, delivery and the healthcare provided for children.
      These data were compared with the results obtained from a study carried out in
      1996. RESULTS: Statistically significant differences were found with regard to
      income, working without a formal employment contract and access to private health
      plans among the families of the children who died. There were also differences in
      access to and quality of prenatal care, frequency of low birth weight and
      neonatal inter-ocurrences. CONCLUSIONS: The employment/unemployment situation was
      decisive in determining the degree of family stability and vulnerability to the
      occurrence of infant deaths, in addition to the conditions of access to and
      quality of healthcare services.

PMID- 19099160
TI  - Chest physiotherapy during immediate postoperative period among patients
      undergoing upper abdominal surgery: randomized clinical trial.
AB  - CONTEXT AND OBJECTIVE: Abdominal surgical procedures increase pulmonary
      complication risks. The aim of this study was to evaluate the effectiveness of
      chest physiotherapy during the immediate postoperative period among patients
      undergoing elective upper abdominal surgery. DESIGN AND SETTING: This randomized
      clinical trial was performed in the post-anesthesia care unit of a public
      university hospital. METHODS: Thirty-one adults were randomly assigned to control
      (n = 16) and chest physiotherapy (n = 15) groups. Spirometry, pulse oximetry and
      anamneses were performed preoperatively and on the second postoperative day. A
      visual pain scale was applied on the second postoperative day, before and after
      chest physiotherapy. The chest physiotherapy group received treatment at the post
      anesthesia care unit, while the controls did not. Surgery duration, length of
      hospital stay and postoperative pulmonary complications were gathered from
      patients' medical records. RESULTS: The control and chest physiotherapy groups
      presented decreased spirometry values after surgery but without any difference
      between them (forced vital capacity from 83.5 +/- 17.1% to 62.7 +/- 16.9% and
      from 95.7 +/- 18.9% to 79.0 +/- 26.9%, respectively). In contrast, the chest
      physiotherapy group presented improved oxygen-hemoglobin saturation after chest
      physiotherapy during the immediate postoperative period (p < 0.03) that did not
      last until the second postoperative day. The medical record data were similar
      between groups. CONCLUSIONS: Chest physiotherapy during the immediate
      postoperative period following upper abdominal surgery was effective for
      improving oxygen-hemoglobin saturation without increased abdominal pain.
      Breathing exercises could be adopted at post-anesthesia care units with benefits
      for patients.

PMID- 19099161
TI  - Metabolic syndrome in patients with prostate cancer.
AB  - CONTEXT AND OBJECTIVE: Prostate cancer (PCa) is the second most common cancer
      among men in Brazil. Recently, several studies have hypothesized a relationship
      between PCa and metabolic syndrome (MS). The aim here was to identify an
      association between MS and PCa. DESIGN AND SETTING: Cross-sectional study,
      Fundacao de Beneficencia Hospital de Cirurgia (FBHC) and Universidade Federal de
      Sergipe. METHODS: Laboratory and anthropometric parameters were compared between
      PCa patients (n = 16) and controls (n = 16). RESULTS: The PCa patients showed
      significantly greater frequency of MS than did the controls (p = 0.034). Serum
      glucose was higher and high-density lipoprotein-cholesterol was lower than in the
      controls, although without significant differences. There were significant
      differences in blood pressure (p = 0.029) and waist-to-hip ratio (p = 0.004).
      Pearson linear correlation showed a positive association between waist-to-hip
      ratio and prostate specific antigen (r = 0.584 and p = 0.028). Comparing
      subgroups with and without MS among the PCa patients, significant differences (p
      < 0.05) in weight, height, body mass index, hip circumference and lean body mass
      were observed, thus showing higher central obesity in those with MS. The serum
      glucose values were also higher in MS patients (p = 0.006), thus demonstrating
      that insulin resistance has a role in MS physiopathology. CONCLUSIONS: Our study
      suggests that MS may exert an influence on the development of PCa. However, it
      would be necessary to expand the investigation field with larger sample sizes and
      cohorts studied, to test the hypothesis generated in this study.

PMID- 19099162
TI  - Teriparatide (recombinant human parathyroid hormone 1-34) in postmenopausal women
      with osteoporosis: systematic review.
AB  - CONTEXT AND OBJECTIVE: Osteoporosis is defined as a disease characterized by low
      bone mass and deterioration of the bone tissue microarchitecture. Teriparatide
      stimulates the formation and action of osteoblasts, which are responsible for
      bone formation, thus promoting bone tissue increase. The aim was to assess the
      effectiveness and safety of teriparatide for treating postmenopausal
      osteoporosis. METHODS: A systematic review was conducted using the Cochrane
      Collaboration methodology. RESULTS: 1) Teriparatide 20 microg or 40 microg versus
      placebo: there was a benefit from teriparatide, considering the following
      outcomes: reduction in the number of new vertebral and non-vertebral fractures,
      and increased whole-body, lumbar and femoral bone mineral density. 2)
      Teriparatide 40 microg versus alendronate 10 mg/day for 14 months: there was no
      statistical difference regarding the incidence of new vertebral or non-vertebral
      fractures, although in the group that received teriparatide there was greater
      bone mineral density increase in the whole body, lumbar column and femur. 3)
      Estrogen plus teriparatide 25 microg versus estrogen: there was a benefit,
      considering the following outcomes: reduction in the number of new vertebral
      fractures, and increased whole-body, lumbar and femoral bone mineral density
      after three years. CONCLUSIONS: When teriparatide is intermittently administered
      in low doses, it reduces the incidence of vertebral fractures (67%) and non
      vertebral fractures (38%) and increases bone mineral density in the lumbar column
      and femur. There is a need for studies with longer observation in order to allow
      conclusions regarding the safety and duration of the therapeutic effects.

PMID- 19099163
TI  - Association between obesity and asthma among teenagers.
AB  - CONTEXT AND OBJECTIVE: Obesity and asthma are serious and growing problems. Since
      adipose tissue produces inflammatory substances, the aim of this study was to
      estimate the prevalence of asthma among students at schools in Sao Jose do Rio
      Preto (Phase 1), and to corroborate the hypothesis for an association between
      obesity and asthma among these students (Phase 2). DESIGN AND SETTING: Cross
      sectional study at Faculdade de Medicina de Sao Jose do Rio Preto (Famerp).
      METHODS: The study consisted of two successive and dependent stages. Phase I was
      a cross-sectional study on 4103 randomly selected students (13-14 years old), to
      determine the prevalence and severity of asthma. Phase II was an analytical cross
      sectional study on 431 students (190 asthmatics and 231 non-asthmatics) from
      Phase I, to evaluate the hypothesis of an association between obesity measured by
      the body mass index (BMI) and asthma. To diagnose asthma and obesity, the
      criteria of the International Study of Asthma and Allergies in Childhood (ISAAC)
      and the chart from the Centers for Disease Control (CDC; 2000) were used. The
      data were analyzed using Student's t test. RESULTS: We found that 5.6% of the
      students analyzed in Phase I were asthmatic. The BMI among the asthmatic students
      (21.84 kg/m(2)) was higher than the BMI among the non-asthmatics (21.73 kg/m(2)),
      although the p value was 0.766. CONCLUSION: In our study group, we did not find
      any association between increased BMI and the prevalence of asthma.

PMID- 19099164
TI  - Absence of the musculocutaneous nerve: a rare anatomical variation with possible
      clinical-surgical implications.
AB  - CONTEXT: The musculocutaneous nerve is one of the terminal branches of the
      lateral fasciculus of the brachial plexus, and is responsible for innervation of
      the flexor musculature of the elbow and for skin sensitivity on the lateral
      surface of the forearm. Its absence has been described previously, but its real
      prevalence is unknown. CASE REPORT: A case of absence of the musculocutaneous
      nerve that was observed during the dissection of the right arm of a male cadaver
      is described. The area of innervation was supplied by the median nerve. From
      this, three branches emerged: one to the coracobrachialis muscle, another to the
      biceps brachii muscle and the third to the brachialis muscle. This last branch
      continued as a lateral antebrachial cutaneous nerve. This is an anatomical
      variation that has clinical-surgical implications, considering that injury to the
      median nerve in this case would have caused unexpected paralysis of the flexor
      musculature of the elbow and hypoesthesia of the lateral surface of the forearm.

PMID- 19099165
TI  - Kidney failure in the elderly due to hypothyroidism: a case report.
AB  - CONTEXT: Hypothyroidism is more prevalent in the elderly and its symptoms can be
      confused with other changes due to aging. Doctors caring for the elderly need to
      be attentive to this diagnostic possibility. This case report case is notable not
      only because it presents a rare complication of hypothyroidism (kidney failure),
      but also because patients with chronic kidney failure of any etiology may suffer
      increased renal dysfunction as a result. CASE REPORT: This was a 66-year-old male
      outpatient with a history of generalized edema over the preceding eight years,
      with periods of worsening, that was intractable to treatment with diuretics.
      Physical examination revealed bradycardia (heart rate: 52 bpm), pallor, dry and
      infiltrated skin, macroglossia, edema in the lower limbs and a palpable thyroid
      with hard consistency. Laboratory tests showed: creatinine 3.9 mg/dl; urea 95
      mg/dl; potassium 6.0 mEq/l; thyroid-stimulating hormone > 100 mUI/ml;
      triiodothyronine 0.01 ng/dl; free thyroxin 0.01 ng/dl; antithyroglobulin 31 IU/ml
      (normal values: < 40 IU/ml); antithyroperoxidase 85 IU/ml (normal values: < 15
      IU/ml); creatinine clearance 30 ml/min/1.73 m(2); and proteinuria 122 mg/24 h.
      After five months of treatment with thyroxin (100 mcg/day), the patient returned
      without any symptoms and presented the following test results: urea 48 mg/dl;
      creatinine 1.4 mg/dl; creatinine clearance 67 ml/min/1.73 m(2); potassium 4.2
      mEq/l; thyroid-stimulating hormone: 20.85 mUI/ml; free thyroxin: 0.71 ng/dl.
      Hypothyroidism alone can cause renal impairment or worsen renal function in
      preexisting illnesses. Its treatment can stabilize the clinical condition, or
      possibly improve it.

PMID- 19099166
TI  - Epithelioid hemangioma of the colon: a case report.
AB  - CONTEXT: Epithelioid hemangioma or angiolymphoid hyperplasia with eosinophilia is
      an uncommon benign vascular neoplasm that is usually located on the face or neck.
      Exceptionally, it has been described affecting the colon, with only two such
      cases described in the worldwide literature. The aim here was to present a case
      of primary epithelioid hemangioma of the sigmoid colon with confirmation by
      immunohistochemical examination. CASE REPORT: A 37-year-old woman had had a
      complaint of intermittent abdominal pain for six months. Two months after the
      condition started, she began to present changes in her intestinal habit, with
      evacuations containing blood and mucus and a weight loss of 4 kg over this
      period. At physical examination, a palpable mass was noted in the lower left
      quadrant of the abdomen. Neoplasia of the colon was clinically suspected and she
      underwent colonoscopy. This demonstrated the presence of a vegetating sessile
      lesion of approximately 5 cm in diameter, at a distance of 36 cm from the anal
      margin. It occupied 80% of the intestinal lumen. A biopsy collected during the
      examination suggested a diagnosis of neoplasia of vascular origin. After surgical
      resection, histopathological examination of the resected specimen confirmed the
      diagnosis of epithelioid hemangioma of the colon, which was backed up by the
      immunohistochemical panel (factor VIII, Ki-67, CD-34). At present, three years
      after the surgery, the patient is asymptomatic, she has recovered her normal
      weight and she has normal findings from control colonoscopy. Despite the rarity
      of neoplasia of vascular origin, this possibility should be considered in the
      differential diagnosis for colorectal tumors.

PMID- 19099167
TI  - Clinicopathological features of 45,X/46,Xidic(Y) mosaicism and therapeutic
      implications: case report.
AB  - CONTEXT: 45,X/46,Xidic(Y) mosaicism demands careful and thorough study because of
      both its variable clinical features and its potential complications. CASE REPORT:
      The present case relates to a three-year-old girl with the mosaic karyotype
      46,X,idic(Y)(q11.2)[23]/45,X[6]. She had no signs of virilization or Turner's
      syndrome phenotype, but she was referred to our hospital because she presented
      reduced growth rate, abnormal facies and a melanotic nevus. After examination,
      she underwent prophylactic gonadectomy because of the risk of gonadoblastoma.
      Cytogenetic analysis on the streak gonads and blood showed significant
      differences in the 45,X cell line between these two tissues. The presence of the
      sex-determining region Y (SRY) gene did not determine male differentiation, which
      meant in the present case that the predominance of the X cell line in the gonadal
      tissue was probably due to the determining factor for female sexual
      differentiation.

PMID- 19099168
TI  - The strengths and difficulties questionnaire: validation study in French school
      aged children and cross-cultural comparisons.
AB  - OBJECTIVES: To examine the psychometric properties of the French version of the
      strengths and difficulties questionnaire (SDQ), compare estimates of child mental
      health problems and SDQ scores across France, US and UK. METHODS: The French
      version of the parent-reported SDQ was administered to the parents of a
      representative sample of 1,348 French children aged 6-11 years old. The response
      rate was 57.6%. We performed three scoring methods and examined their association
      with socio-demographic data. French SDQ scores were compared with SDQ scores from
      US and UK national surveys. RESULTS: The French cut-off points for the scoring
      bands were similar to those of the UK and US, with a few exceptions (peer
      relationship problems, prosocial behaviour). The internal consistency of the SDQ
      subscales was acceptable with Cronbach alpha coefficients ranging from 0.46 for
      peer relationship problems to 0.74 for hyperactivity/inattention. Known socio
      demographic risk factors were associated with SDQ scoring method. For most SDQ
      scores, differences between France and the UK were smaller (5%) than those
      between France and the US. CONCLUSION: The study provided good support for the
      validity of the parent-reported SDQ in France as well as evidence for the
      usefulness of the SDQ as a promising screening instrument for epidemiological
      research and clinical purposes.

PMID- 19099169
TI  - Did the introduction of 'dangerousness' and 'risk of harm' criteria in mental
      health laws increase the incidence of suicide in the United States of America?
AB  - INTRODUCTION: Mental health laws limiting involuntary admission to psychiatric
      hospitals to those assessed to be dangerous or at risk of harm to themselves or
      others (obligatory dangerousness criteria, ODC) have been introduced in almost
      every jurisdiction in the United States of America. Some mentally ill patients,
      who might have been admitted for treatment under previous laws, but who were not
      admitted because they were not considered 'dangerous', could subsequently have
      committed suicide. In order to investigate whether or not suicide rates increased
      after the introduction of ODC, we examined suicide statistics from 48 states and
      the District of Columbia. METHODS: We aligned suicide statistics according to the
      year in which ODC were introduced in each jurisdiction. We then examined suicide
      rates in the 15 years before and after the introduction of ODC and trends in
      national and state suicide rates between 1960 and 1990. Meta-analysis was used to
      examine differences in suicide rates in the year immediately before and in the
      year immediately after the introduction of ODC. RESULTS: Between 1968 and 1977,
      the decade in which ODC were introduced in the majority of jurisdictions,
      national suicide rates increased from under 11 per 100,000 per annum to over 12.5
      per 100,000 per annum. The increase in many jurisdictions occurred in the years
      immediately before the introduction of ODC. The introduction of ODC was
      associated with a non-significant increase in suicide rates in the 49
      jurisdictions. There was a significant increase in suicide rates after the
      introduction of ODC in the 19 jurisdictions that introduced ODC prior to 1976.
      CONCLUSIONS: The introduction of ODC might have contributed to increased suicide
      rates prior to 1976. However, a simpler explanation for the finding is that
      national suicide rates were rising for other reasons in the same period. We did
      not find an increase in suicide rates in the jurisdictions where ODC mental
      health laws were introduced after 1976. Hence, the findings of this study do not
      support the conclusion that ODC laws have a measurable impact on suicide rates.

PMID- 19099171
TI  - Stress urinary incontinence after transobturator mesh for cystocele repair.
AB  - Cystocele repair can lead to de novo stress urinary incontinence (SUI) or
      exacerbate pre-existing SUI. This study was designed to determine the effect of
      cystocele repair by transobturator mesh on SUI. In a retrospective observational
      study, we saw 93 patients after a transobturator mesh procedure. Of those, 57
      women had not undergone a concomitant anti-incontinence procedure. We analyzed
      their clinical data and ultrasound datasets. At a median follow-up of 9 months,
      21 of 24 preoperatively stress incontinent women reported cure/improvement, one
      patient reported worsened SUI. Seven of 33 preoperatively continent women
      complained of de novo SUI. There is a net positive effect on SUI (McNemar chi(2)
      exact test p = 0.013) after transobturator mesh. A narrower gap between symphysis
      pubis and mesh was associated with a positive outcome (p = 0.015 on ANOVA).
      Transobturator mesh for cystocele repair appears to have a net positive effect on
      SUI.

PMID- 19099172
TI  - Kawasaki disease in an 8-day-old neonate.

PMID- 19099174
TI  - Results of laparoscopic liver resection: retrospective study of 68 patients.
AB  - BACKGROUND: Although an increasing number of reports and publications have dealt
      with the laparoscopic approach to liver resection, this procedure remains
      uncommon, and its feasibility, safety and effectiveness are still not
      established. There are few reports of the advantages of this approach on
      postoperative recovery. METHODS: From December 1997 to March 2007, laparoscopic
      hepatic resection were performed in 68 patients. RESULTS: There were 52 malignant
      tumors (36 hepatocellular carcinomas, three intrahepatic cholangiocarcinomas, one
      cystadenocarcinoma, liver metastases from ten colorectal carcinomas and two other
      organs) and 16 benign lesions among our 68 patients. Fifteen patients with
      hepatocellular carcinoma had cirrhosis. The mean tumor size was 3.1 +/- 1.8 cm
      (range 1.0-14.0 cm), and the tumors were located in every liver segment except
      segment I. Liver resection was anatomical in 17 patients and consisted of a
      lobectomy in four patients and a lateral segmentectomy in 13 patients. Non
      anatomical resections were performed in 51 patients. The operative time was 214
      +/- 93 min. Mean blood loss was 393 +/- 564 g. A hand-assisted laparoscopic
      method or mini-laparotomy method was required in 35 patients (51.4%). Operative
      complications occurred mainly in our early cases and included three patients
      (4.4%) with operative bleeding, 2 of whom (2.9%) requiring a conversion to open
      surgery. Postoperative complications occurred in seven patients (10.0%), and two
      of then eventually required a re-operation. The mean hospital stay was 17 days.
      There were no complications in the more recent cases. CONCLUSIONS: The
      laparoscopic approach for liver tumors is feasible, if the indication is
      carefully selected. The safety of this procedure depends on the surgical
      experience of the surgeon and team and the availability of the necessary
      technology.

PMID- 19099173
TI  - Developmental signaling in myocardial progenitor cells: a comprehensive view of
      Bmp- and Wnt/beta-catenin signaling.
AB  - The tight regulation of different signaling systems and the transcriptional and
      translational networks during embryonic development have been the focus of
      embryologists in recent decades. Defective developmental signaling due to genetic
      mutation or temporal and region-specific alteration of gene expression causes
      embryonic lethality or accounts for birth defects (e.g., congenital heart
      disease). The formation of the heart requires the coordinated integration of
      multiple cardiac progenitor cell populations derived from the first and second
      heart fields and from cardiac neural crest cells. This article summarizes what
      has been learned from conditional mutagenesis of Bmp pathway components and the
      Wnt effector, beta-catenin, in the developing heart of mice. Although Bmp
      signaling is required for cardiac progenitor cell specification, proliferation,
      and differentiation, recent studies have demonstrated distinct functions of
      Wnt/beta-catenin signaling at various stages of heart development.

PMID- 19099175
TI  - The awakened intraspinal glass shard.
AB  - Penetrating spinal injuries from foreign bodies are an exceedingly rare
      pathological entity. In this report we present an unusual clinical report of an
      in-driven shard of glass in the cervical spine that remained without symptoms for
      many years and became symptomatic possibly because of narrowing of the diameter
      of the vertebral canal.

PMID- 19099176
TI  - Tethered cord syndrome in identical twins.
AB  - The diagnosis of tethered cord syndrome (TCS) without typical conus medullaris
      symptoms and the radiological features such as a low set conus medullaris or
      dysraphic malformation is difficult. We report 11 year old identical twin
      brothers with TCS associated with the conus at the normal level. Their presenting
      symptom was progressive leg pain and both patients underwent surgical
      interruption of the filum terminale. The pain recurred in one patient treated
      surgically only after symptom became worse but resolved immediately in the other
      sibling treated promptly. We indicate the importance of early diagnosis and
      treatment of TCS to obtain excellent long-term outcome despite the absence of a
      low set conus or specific symptoms. Furthermore, when a twin or sibling of an
      affected person has neurological symptoms and the cutaneous signature of spinal
      dysraphism, radiological examination should be performed to establish the cause.

PMID- 19099177
TI  - A combined microdialysis and FDG-PET study of glucose metabolism in head injury.
AB  - BACKGROUND: Microdialysis continuously monitors the chemistry of a small focal
      volume of the cerebral extracellular space. Positron emission tomography (PET)
      establishes metabolism of the whole brain but only for the scan's duration. This
      study's objective was to apply these techniques together, in patients with
      traumatic brain injury, to assess the relationship between microdialysis
      (extracellular glucose, lactate, pyruvate, and the lactate/pyruvate (L/P) ratio
      as a marker of anaerobic metabolism) and PET parameters of glucose metabolism
      using the glucose analogue [(18)F]-fluorodeoxyglucose (FDG). In particular, we
      aimed to determine the fate of glucose in terms of differential metabolism to
      pyruvate and lactate. MATERIALS AND METHODS: Microdialysis catheters (CMA70 or
      CMA71) were inserted into the cerebral cortex of 17 patients with major head
      injury. Microdialysis was performed during FDG-PET scans with regions of interest
      for PET analysis defined by the location of the gold-tipped microdialysis
      catheter. Microdialysate analysis was performed on a CMA600 analyser. FINDINGS:
      There was significant linear relationship between the PET-derived parameter of
      glucose metabolism (regional cerebral metabolic rate of glucose; CMRglc) and
      levels of lactate (r = 0.778, p < 0.0001) and pyruvate (r = 0.799, p < 0.0001),
      but not with the L/P ratio. CONCLUSION: The results suggest that in this
      population of patients, glucose was metabolised to both lactate and pyruvate, but
      was not associated with an increase in the L/P ratio. This suggests an increase
      in glucose metabolism to both lactate and pyruvate, as opposed to a shift towards
      anaerobic metabolism.

PMID- 19099178
TI  - Technical analysis of dual channel pulse generators used in deep brain
      stimulation; a safety evaluation.
AB  - BACKGROUND: A sudden failure of implantable pulse generators (IPG) occurred in 15
      out of 143 units during the last 4 years in our patients. This corresponds to a
      failure rate of 10.5%. In all cases, the connection between the causes of battery
      and electronic circuit was found defective in the destructive analysis. In order
      to better understand the failure causes we proceeded to an analysis of explanted
      IPGs which had reached their normal life span due to depletion of the battery.
      METHOD: A functional test and an intensive destructive analysis were carried out
      in 14 units. The internal parts of the IPG were inspected by light and electron
      microscopy. FINDINGS: Deformations of the connection between battery and
      electronic circuit could be found in 12 out of 14 IPGs. The epoxy bonds, which
      achieve the mechanical fixation between the two contact areas of the bond wires,
      were found separated in 86%. Additionally, in six out of 14 devices the bond
      wires were either found lifted or with cracks as a sign of material fatigue.
      CONCLUSION: Based on these results we conclude that the IPGs of the affected
      series did have a technical weak spot. We presume that this issue appears
      systematically and not randomly or triggered by an unusual action of the patient.

PMID- 19099180
TI  - Commercial dressings for burns versus sweet ancient remedy.

PMID- 19099181
TI  - The fourth year of Internal and Emergency Medicine.

PMID- 19099183
TI  - DyP-type peroxidases comprise a novel heme peroxidase family.
AB  - Dye-decolorizing peroxidase (DyP) is produced by a basidiomycete (Thanatephorus
      cucumeris Dec 1) and is a member of a novel heme peroxidase family (DyP-type
      peroxidase family) that appears to be distinct from general peroxidases. Thus
      far, 80 putative members of this family have been registered in the PeroxiBase
      database (http://peroxibase.isbsib.ch/) and more than 400 homologous proteins
      have been detected via PSI-BLAST search. Although few studies have characterized
      the function and structure of these proteins, they appear to be bifunctional
      enzymes with hydrolase or oxygenase, as well as typical peroxidase activities.
      DyP-type peroxidase family suggests an ancient root compared with other general
      peroxidases because of their widespread distribution in the living world. In this
      review, firstly, an outline of the characteristics of DyP from T. cucumeris is
      presented and then interesting characteristics of the DyP-type peroxidase family
      are discussed.

PMID- 19099182
TI  - Modulation of chemokine receptor activity through dimerization and crosstalk.
AB  - Chemokines are small, secreted proteins that bind to the chemokine receptor
      subfamily of class A G protein-coupled receptors. Collectively, these receptor
      ligand pairs are responsible for diverse physiological responses including immune
      cell trafficking, development and mitogenic signaling, both in the context of
      homeostasis and disease. However, chemokines and their receptors are not isolated
      entities, but instead function in complex networks involving homo- and
      heterodimer formation as well as crosstalk with other signaling complexes. Here
      the functional consequences of chemokine receptor activity, from the perspective
      of both direct physical associations with other receptors and indirect crosstalk
      with orthogonal signaling pathways, are reviewed. Modulation of chemokine
      receptor activity through these mechanisms has significant implications in
      physiological and pathological processes, as well as drug discovery and drug
      efficacy. The integration of signals downstream of chemokine and other receptors
      will be key to understanding how cells fine-tune their response to a variety of
      stimuli, including therapeutics.

PMID- 19099184
TI  - The trefoil factor family - small peptides with multiple functionalities.
AB  - The trefoil factor family (TFF) comprises a group of small peptides which are
      highly expressed in tissues containing mucus-producing cells - especially in the
      mucosa lining the gastrointestinal tract. The peptides seem crucial for
      epithelial restitution and may work via other pathways than the conventional
      factors involved in restitution. In vitro studies have shown that the TFFs
      promote restitution using multiple mechanisms. The peptides also have other
      functionalities including interactions with the immune system. Moreover,
      therapeutic effects of the TFFs have been shown in several animal models of
      gastrointestinal damage. Still it is not clear which of their in vitro properties
      are involved in the in vivo mode of action. This review describes the TFF family
      with emphasis on their biological properties and involvement in mucosal
      protection and repair.

PMID- 19099185
TI  - Mcl-1 is a potential therapeutic target in multiple types of cancer.
AB  - Resistance to apoptosis is a common challenge in human malignancies contributing
      to both progress of cancer and resistance to conventional therapeutics.
      Abnormalities in a variety of cell intrinsic and extrinsic molecular mechanisms
      cooperatively promote tumor formation. Therapeutic approaches that specifically
      target components of these molecular mechanisms are getting widespread attention.
      Mcl-1 is a highly expressed pro-survival protein in human malignancies and its
      cellular expression is tightly regulated via multiple mechanisms. Mcl-1 differs
      from other members of the Bcl-2 family in having a very short half-life. So
      inhibition of its expression and/or neutralization of its anti-apoptotic function
      will rapidly make Mcl-1-dependent cells more susceptible to apoptosis and provide
      an opportunity to combat several types of cancers. This review summarizes the
      current knowledge on the regulation of Mcl-1 expression and discusses the
      alternative approaches targeting Mcl-1 in human cancer cells whose survivals
      mainly depend on Mcl-1.

PMID- 19099187
TI  - A novel interplay between membrane and nuclear melatonin receptors in human
      lymphocytes: significance in IL-2 production.
AB  - Human lymphocyte melatonin, through membrane and nuclear receptors binding, acts
      as an activator in IL-2 production. Antagonism of membrane melatonin receptors
      using luzindole exacerbates the drop of the IL-2 production induced by PGE(2) in
      peripheral blood mononuclear and Jurkat cells. This paper studies the melatonin
      membrane and nuclear receptors interplay in PGE(2)-diminished IL-2 production.
      The decrease in IL-2 production after PGE(2) and/or luzindole administration
      correlated with downregulation in the nuclear receptor RORalpha. We also
      highlighted a role of cAMP in the pathway, because forskolin mimicked the effects
      of luzindole and/or PGE(2) in the RORalpha expression. Finally, a significant
      RORalpha downregulation was observed in T cells permanently transfected with
      inducible MT(1) antisense. In conclusion, we show a novel connection between
      melatonin membrane receptor signalling and RORalpha expression, opening a new way
      to understand melatonin regulation in lymphocyte physiology.

PMID- 19099188
TI  - Chromatin structure contribution to the synaptonemal complex formation.
AB  - Meiosis is a key cellular and molecular process for sexual reproduction
      contributing to the genetic variability of organisms. This process takes place
      after DNA replication and consists in a double cellular division, giving rise to
      four haploid daughter cells or gametes. Meiotic recombination between homologous
      chromosomes, in the meiotic prophase I, is mediated by a tripartite structure
      named Synaptonemal Complex (SC). The SC is a peptidic scaffold in which the
      chromatin of homologous chromosomes is organized during the pachytene stage,
      holding chromosomes together until the meiotic recombination and genetic exchange
      have taken place. The role of chromatin structure in formation of the SC and the
      meiotic recombination at meiotic prophase I remain largely unknown. In this
      review we address the epigenome contribution to the SC formation at meiotic
      prophase I, with particular attention on the chromatin structure modifications
      occurring during the sub-stages of meiotic prophase I.

PMID- 19099186
TI  - Molecular mechanisms of BK channel activation.
AB  - Large conductance, Ca(2+)-activated potassium (BK) channels are widely expressed
      throughout the animal kingdom and play important roles in many physiological
      processes, such as muscle contraction, neural transmission and hearing. These
      physiological roles derive from the ability of BK channels to be synergistically
      activated by membrane voltage, intracellular Ca(2+) and other ligands. Similar to
      voltage-gated K(+) channels, BK channels possess a pore-gate domain (S5-S6
      transmembrane segments) and a voltage-sensor domain (S1-S4). In addition, BK
      channels contain a large cytoplasmic C-terminal domain that serves as the primary
      ligand sensor. The voltage sensor and the ligand sensor allosterically control
      K(+) flux through the pore-gate domain in response to various stimuli, thereby
      linking cellular metabolism and membrane excitability. This review summarizes the
      current understanding of these structural domains and their mutual interactions
      in voltage-, Ca(2+)- and Mg(2+)-dependent activation of the channel.

PMID- 19099190
TI  - The continuing disappearance of "pure" Ca2+ buffers.
AB  - Advances in the understanding of a class of Ca(2+)-binding proteins usually
      referred to as "Ca(2+) buffers" are reported. Proteins historically embraced
      within this group include parvalbumins (alpha and beta), calbindin-D9k, calbindin
      D28k and calretinin. Within the last few years a wealth of data has accumulated
      that allow a better understanding of the functions of particular family members
      of the >240 identified EF-hand Ca(2+)-binding proteins encoded by the human
      genome. Studies often involving transgenic animal models have revealed that they
      exert their specific functions within an intricate network consisting of many
      proteins and cellular mechanisms involved in Ca(2+) signaling and Ca(2+)
      homeostasis, and are thus an essential part of the Ca(2+) homeostasome. Recent
      results indicate that calbindin-D28k, possibly also calretinin and oncomodulin,
      the mammalian beta parvalbumin, might have additional Ca(2+) sensor functions,
      leaving parvalbumin and calbindin-D9k as the only "pure" Ca(2+) buffers.

PMID- 19099189
TI  - Welcome the family of FANCJ-like helicases to the block of genome stability
      maintenance proteins.
AB  - The FANCJ family of DNA helicases is emerging as an important group of proteins
      for the prevention of human disease, cancer, and chromosomal instability. FANCJ
      was identified by its association with breast cancer, and is implicated in
      Fanconi Anemia. Proteins with sequence similarity to FANCJ are important for
      maintenance of genomic stability. Mutations in genes encoding proteins related to
      FANCJ, designated ChlR1 in human and Chl1p in yeast, result in sister chromatid
      cohesion defects. Nematodes mutated in dog-1 show germline as well as somatic
      deletions in genes containing guanine-rich DNA. Rtel knockout mice are embryonic
      lethal, and embryonic stem cells show telomere loss and chromosomal instability.
      FANCJ also shares sequence similarity with human XPD and yeast RAD3 helicases
      required for nucleotide excision repair. The recently solved structure of XPD has
      provided new insight to the helicase core and accessory domains of sequence
      related Superfamily 2 helicases. The functions and roles of members of the FANCJ
      like helicase family will be discussed.

PMID- 19099191
TI  - The role of P-glycoprotein/cellular prion protein interaction in multidrug
      resistant breast cancer cells treated with paclitaxel.
AB  - We previously reported that treatment with P-glycoprotein (P-gp) substrates
      promotes in vitro invasion in multidrug-resistant (MDR) breast cancer cells. This
      effect is initiated by the P-gp pump function and mediated by interaction of P-gp
      with some unknown component(s). However, the underlying mechanism(s) remains
      poorly understood. Here we confirm a novel physical interaction between P-gp and
      cellular prion protein (PrP(c)). Blocking P-gp activity or depletion of PrP(c)
      inhibited paclitaxel (P-gp substrate)- induced invasion. Paclitaxel further
      facilitated the formation of P-gp/PrP(c) clusters residing in caveolar domains
      and promoted the association of P-gp with caveolin-1. Both caveolin-1 and the
      integrity of caveolae were required for the drug-induced invasion. In addition,
      the P-gp/PrP(c) complex also played an important role in anti-apoptotic activity
      of MCF7/Adr cells.These data provide new insights into the mode by which MDR
      breast cancers evade cytotoxic attacks from P-gp substrates and also suggest a
      role for P-gp/ PrP(c) interaction in this process.

PMID- 19099192
TI  - Nuclear functions of heterogeneous nuclear ribonucleoproteins A/B.
AB  - The hnRNP A/B proteins are among the most abundant RNA-binding proteins, forming
      the core of the ribonucleoprotein complex that associates with nascent
      transcripts in eukaryotic cells. There are several paralogs in this subfamily,
      each of which is subject to alternative transcript splicing and post
      translational modifications. The structural diversity of these proteins generates
      a multitude of functions that involve interactions with DNA or, more commonly,
      RNA. They also recruit regulatory proteins associated with pathways related to
      DNA and RNA metabolism, and appear to accompany transcripts throughout the life
      of the mRNA. We have highlighted here recent progress in elucidation of molecular
      mechanisms underlying the roles of these hnRNPs in a wide range of nuclear
      processes, including DNA replication and repair, telomere maintenance,
      transcription, pre-mRNA splicing, and mRNA nucleo-cytoplasmic export.

PMID- 19099193
TI  - Carbon monoxide releasing molecules: new insights for anticoagulation strategy in
      sepsis.
AB  - Sepsis is a common and serious medical condition caused by hemorrhage, trauma, or
      abdominal surgery. Despite new understanding and much progress in therapies that
      specifically interfere with an interesting target, sepsis remains the leading
      causes of death in critically ill patients. Various therapies have been studied,
      but the majority of these treatments fail in clinical trials. It is clear that
      all septic patients exhibit coagulation abnormalities. These abnormalities range
      from subtle to marked activation of coagulation system, and finally to fulminant
      DIC. Studies confirmed that carbon monoxide has important cytoprotective function
      and anti-inflammatory properties. Until now, the question of whether CO plays a
      critical role in improving the coagulation system and then decreasing mortality
      during sepsis has not yet been definitely answered. Attempts to confirm this
      strategy may lead to new directions in the study of treatment of sepsis and the
      development of a novel agent for this disorder.

PMID- 19099194
TI  - Mid-anaphase arrest in S. cerevisiae cells eliminated for the function of Cin8
      and dynein.
AB  - S. cerevisiae anaphase spindle elongation is accomplished by the overlapping
      function of dynein and the kinesin-5 motor proteins, Cin8 and Kip1. Cin8 and
      dynein are synthetically lethal, yet the arrest phenotypes of cells eliminated
      for their function had not been identified. We found that at a non-permissive
      temperature, dyn1 Delta cells that carry a temperature-sensitive cin8 - 3
      mutation arrest at mid-anaphase with a unique phenotype, which we named TAN (two
      microtubule asters in one nucleus). These cells enter anaphase, but fail to
      proceed through the slow phase of anaphase B. At a permissive temperature, dyn1
      Delta, cin8 - 3 or dyn1 Delta cin8 - 3 cells exhibit perturbed spindle midzone
      morphologies, with dyn1Delta cin8 - 3 anaphase spindles also being profoundly
      bent and nonrigid. Sorbitol, which has been suggested to stabilize microtubules,
      corrects these defects and suppresses the TAN phenotype. We conclude that dynein
      and Cin8 cooperate in anaphase midzone organization and influence microtubule
      dynamics, thus enabling progression through the slow phase of anaphase B.

PMID- 19099195
TI  - Synchronous mixed germ cell tumor of the pineal gland and suprasellar region with
      a predominant angiomatous component: a diagnostic challenge.
AB  - We present a case of synchronous involvement of the pineal and suprasellar
      regions by a mixed germ cell tumor comprising germinoma and yolk sac tumor
      components, with a predominant angiomatous component. To our knowledge, it is the
      first case of this nature to be reported in the literature. Usually, synchronous
      lesions of this kind are pure germinomas, and some clinicians will forgo a biopsy
      and assume a germinoma histology if the serum beta-human chorionic gonadotrophin
      (HCG) is <50 IU/l and the alpha-fetoprotein (AFP) is within normal limits.
      Secondly, if a biopsy is performed on a lesion that has a prominent angiomatous
      component, the diagnostic germ cell tumor may be missed at the time of the
      biopsy. In order to alert clinicians and pathologists to this rare entity, the
      case is discussed with particular reference to difficulties that were encountered
      in rendering an accurate diagnosis, and the associated management implications.

PMID- 19099196
TI  - Identification of patients who may benefit from the prophylactic cranial
      radiotherapy among breast cancer patients with brain metastasis.
AB  - BACKGROUND: To identify the candidates for prophylactic cranial radiotherapy
      (PCI) among the patients with early and advanced-stage breast cancer. METHODS:
      The demographic, pathologic and clinical features and survival results of 182
      brain metastatic breast cancer patients treated with cranial radiotherapy were
      examined. RESULTS: Early stage patients who progressed with isolated brain
      metastasis had longer survival (13 months vs. 4 months P = 0.006). Lobular/mixed
      type histology (P = 0.033), high nuclear (P = 0.046) and high histological grade
      (P = 0.034) were the prognostic factors for isolated brain metastases. The most
      significant factor for the time to brain metastasis was the number of involved of
      lymph nodes (P = 0.004). In 60% of 148 patients with metastatic breast cancer, a
      progression with isolated brain metastasis was developed while the systemic
      disease was under control. Isolated brain metastasis progression was related to
      the presence of the hepatic metastasis at the first relapse (P = 0.001) and with
      ErbB-2 overexpression (P = 0.034). The time to the brain metastasis from the
      first extracerabral metastasis was associated with the high nuclear grade (P =
      0.040) and with chemoresistance (P = 0.037). The median survival time after the
      brain metastases in chemosensitive patients was longer than in chemoresistant
      patients (8 months vs. 3 months P = 0.044). In chemoresistant patients (P =
      0.0028) and/or in triple negative patients (P = 0.05) the development of the
      brain metastasis was early and the survival after brain metastasis was short.
      DISCUSSIONS: Since there is a tendency to early brain metastasis in early stage
      patients with high-grade, lobular/mixed type histology tumors and with a high
      number of involved lymph nodes, the value of PCI can be explored in these
      patients by a well designed prospective trial. Advanced stage chemosensitive
      patients with ErbB-2 over-expression and/or with hepatic metastasis at their
      first relapse may be candidates for PCI. There is no place for PCI in
      chemoresistant and triple-negative breast cancer patients.

PMID- 19099197
TI  - Contributions of biological tumor parameters to the incorporation rate of L: 
      [methyl-(11)C] methionine into astrocytomas and oligodendrogliomas.
AB  - We compared the tumor uptake of (11)C-methionine (MET) with positron emission
      tomography (PET) with the results of a pathological analysis to examine the
      proliferative potential and microvessel density measured with immunostaining for
      MIB-1 and factor VIII, respectively, from 33 patients with glioma. The MET uptake
      in oligodendrogliomas was significantly greater than that in grade 2 astrocytomas
      and comparable to those in grade 3 and 4 astrocytomas. The MIB-1 index of
      oligodendroglioma meanwhile was comparable to that of grade 2 astrocytoma. The
      microvessel area in oligodendroglioma was significantly greater than that in
      grade 2 astrocytomas and comparable to those in grade 3 and 4 astrocytomas.
      According to a multivariate statistical analysis, MET uptake ratio was closely
      correlated with the MIB-1 index among astrocytomas. An increase in the
      microvessel area in the oligodendrogliomas contributed to the higher MET uptake
      among the tumors with a low-proliferative index. This information is important
      for interpreting the results of MET-PET studies for clinical use.

PMID- 19099198
TI  - Radiation-induced optic neuritis after pituitary adenoma radiosurgery in a
      patient with multiple sclerosis: case report.
AB  - OBJECTIVE AND IMPORTANCE: To describe a rare case of optic neuritis onset after
      Gamma Knife stereotactic radiosurgery. CLINICAL PRESENTATION: Nine years after
      transsphenoidal subtotal resection of a pituitary adenoma, this 43-year-old woman
      had elevated serum prolactin levels and headaches. INTERVENTION: Gamma Knife
      stereotactic radiosurgery to residual pituitary tumor. CONCLUSION: To our
      knowledge, this is the first report of radiation-induced optic neuritis after
      radiosurgery in a patient with multiple sclerosis.

PMID- 19099199
TI  - Extended exposure to alkylator chemotherapy: delayed appearance of
      myelodysplasia.
AB  - OBJECTIVE: A case series of gliomas treated with alkylator-based chemotherapy who
      subsequently developed myelodysplastic syndrome (tMDS) or acute myelocytic
      leukemia (AML). BACKGROUND: Alkylator-based chemotherapy is recognized to be
      leukemogenic; however, it is infrequently described as a delayed consequence of
      anti-glioma treatment. METHODS: Seven patients (4 men; 3 women) ages 34-69 years
      (median 44), with gliomas (3 Grade 2; 4 Grade 3) were treated with surgery, all
      but one with involved-field radiotherapy and all with alkylator-based
      chemotherapy (temozolomide; 6 patients, nitrosoureas; 5 patients, both agents; 5
      patients). RESULTS: Exposure to alkylator-based chemotherapy ranged from 8 to 30
      months (median 24). The diagnosis of tMDS was determined by bone marrow biopsy in
      7 patients. Seven patients showed chromosomal abnormalities consistent with
      chemotherapy induced MDS. Three patients were diagnosed with AML as well (in two
      determined by bone marrow and one at autopsy). Interval from last chemotherapy
      exposure to diagnosis of tMDS/AML ranged from 3 to 31 months (median 24 months).
      Two patients were treated with bone marrow transplantation and 5 received
      supportive care only. Five patients have died, 2 as a consequence of recurrent
      brain tumor, 1 as a complication of transplantation, and 2 due to AML.
      CONCLUSIONS: Although rare, induction of tMDS/AML following extended use of
      alkylator-based chemotherapy may become more relevant with the evolving practice
      to treat gliomas for protracted periods. Future work to determine at risk
      patients would be important.

PMID- 19099200
TI  - Subtelomeric analysis of pediatric astrocytoma: subchromosomal instability is a
      distinctive feature of pleomorphic xanthoastrocytoma.
AB  - Astrocytic neoplasms are genetically heterogeneous; however a low frequency of
      genomic changes has been found in juvenile pilocytic astrocytoma (PA) in
      molecular studies. Concerning pleomorphic xanthoastrocytomas (PXA), recent
      studies have given heterogeneous results for chromosomal alterations. We studied
      the subtelomeric regions of 19 primary astrocytoma tumors. Results were near
      normality for the PA group with relative scarcity of chromosomal imbalances,
      except for the duplication of 3pter in 4/15 and deletion of 21qter in 5/15 of
      them. In contrast, a specific profile was observed in the 4 PXA tumoral samples.
      This involved 3pter, 14qter and 19pter duplication and 4qter, 6qter, 9qter,
      13cen, 17pter, 18qter and 21qter deletion. Our results indicate that the
      chromosomal and genetic aberrations in PXAs differed from those typically
      associated with the diffusely infiltrating astrocytic and oligodendroglial
      gliomas. These genetic differences would likely contribute to the more favorable
      behavior of PXAs and may be helpful for molecular differential diagnosis of
      pediatric cerebral tumors.

PMID- 19099201
TI  - Predictive factors for overall and progression-free survival, and dissemination
      in oligodendroglial tumors.
AB  - The pattern of recurrence and predictive factors for tumor progression,
      dissemination and survival in oligodendroglial tumors were investigated. 56
      consecutive patients with oligodendroglial tumors were retrospectively analyzed
      to determine the predictive significance of various factors, including World
      Health Organization grade, loss of chromosomes 1p and 19q, and
      immunohistochemical features of TP53, O(6)-methylguanine-deoxyribonucleic-acid
      methyltransferase, CD44H, nestin, and Ki-67. Eleven patients developed
      dissemination, and had significantly shorter post-progression survival compared
      to ten patients with local recurrence. Univariate analysis showed that retention
      of chromosome 1p or 19q, Ki-67 labeling index > or = 25%, diffuse expression of
      nestin, and p53 labeling index > or = 10% were unfavorable factors for overall,
      progression-free, and dissemination-free survival. Multivariate analysis showed
      that Ki-67 labeling index > or = 25% and diffuse expression of nestin were
      significant for dissemination-free survival. In conclusion, post-progression
      survival shows significant differences between patients with local and
      disseminated recurrence. Ki-67 labeling index and nestin expression pattern are
      useful markers to predict dissemination.

PMID- 19099202
TI  - Ifosfamide or trofosfamide in patients with intraocular lymphoma.
AB  - We evaluated response, progression-free survival (PFS), overall survival (OS),
      relapse patterns and long-term toxicity of intraocular lymphoma (IOL) patients
      treated with ifosfamide (IFO) or trofosfamide (TRO). In a prospective single
      center study, IFO or TRO were given to 10 patients with IOL. The median patient
      age was 73 (range 46-83) years. Six patients were pretreated with up to four
      treatment regimens for ocular or cerebral lymphoma, and four were therapy-naive.
      All patients responded, including nine complete remissions and one partial
      remission, with a median PFS of 18 (7-36) months. Seven patients relapsed: five
      in the eye and two in the brain. Median OS was 32 (7-37+) months. No long-term
      toxicity was observed in patients treated with IFO or TRO alone. IFO or TRO were
      active and well tolerated in this study. Thus, they may represent suitable
      combination partners for other cytostatics used for PCNSL and IOL treatment.

PMID- 19099203
TI  - Intravitreal bevacizumab treatment of macular edema in central retinal vein
      occlusion: one-year results.
AB  - PURPOSE: To report on the anatomic and visual acuity response after intravitreal
      bevacizumab injection in patients with macular edema due to non-ischemic central
      retinal vein occlusion (CRVO). METHODS: In a retrospective study, 21 consecutive
      patients (21 eyes) with non-ischemic CRVO underwent, on average, 3.7 intravitreal
      bevacizumab injections (1.25 mg). Ophthalmic examination included best corrected
      visual acuity (BCVA) and central retinal thickness (CRT) at baseline and follow
      up visits. Fluorescein angiography was performed at baseline and at follow-up
      visits if needed. Primary outcomes were change of BCVA and CRT. RESULTS: The
      follow-up period for all of the included patients was 12 months. The mean BCVA
      was unchanged at the 12-month examination (baseline: 20/160; 12 months: 20/160)
      (P = 0.771). The mean CRT decreased from 780 microm (standard deviation [SD] +/-
      324 microm) at the baseline to a mean of 462 microm (SD +/- 248 microm) at 12
      months (P < 0.05). CONCLUSION: Intravitreal bevacizumab resulted in a significant
      decrease in CRT without significant improvement of visual acuity in patients with
      non-ischemic CRVO after a follow-up of 12 months.

PMID- 19099204
TI  - Testosterone levels in athletes at rest and exhaustion: effects of calcium
      supplementation.
AB  - The effects of 4 weeks of calcium supplementation on free- and total testosterone
      levels were established in active and sedentary adult males at rest and
      exhaustion. Thirty healthy male athletes were equally divided into three study
      groups, as follows: Group 1-non-exercising subjects receiving 35 mg calcium/kg
      body weight; Group 2-subjects receiving 35 mg calcium/kg body weight undergoing
      training routines for 90 min/day, 5 days a week and Group 3-subjects undergoing
      training routines for 90 min/day, 5 days a week. The testosterone levels were
      determined before and after supplementation, at rest and following a hard
      training routine. The plasma free- and total testosterone levels increased at
      exhaustion before and after supplementation relative to resting values (p <
      0.05). This was also true when active subjects were compared to inactive subjects
      (p < 0.05). Our results show that training results in increased testosterone
      levels in athletes and that the increase is greater if accompanied by calcium
      supplementation, which may be useful for increasing overall athletic performance.

PMID- 19099205
TI  - Characterization and identification of hepatic mRNA related to copper metabolism
      and homeostasis in cattle.
AB  - Copper is an essential trace mineral required for growth and development. Copper
      homeostasis within the cell is mediated by the expression of the Cu transporter
      protein (CTR1), ATPase7A (ATP7A), ATPase7B (ATP7B), Cox17, and Cu chaperone for
      Cu-Zn superoxide dismutase (CCS) which helps to regulate Cu uptake, export, and
      intracellular compartmentalization in non-ruminants. Copper also serves as a
      cofactor of antioxidant, superoxide dismutase1 (SOD1). Liver tissue from eighteen
      Holstein bull calves (average BW 201 +/- 58.5 kg, 7.3 +/- 1.9 months) from a
      previous experiment were utilized to characterize and identify hepatic mRNA
      related to Cu metabolism and homeostasis in cattle. Hepatic Cu concentration was
      determined via flame atomic absorption, and total RNA was extracted using TRI
      reagent and purified using RNeasy. Hepatic Cu concentrations ranged from 86 to
      801 mg of Cu/kg DM. Real-time polymerase chain reaction analysis revealed that
      CTR1, ATP7A, and ATP7B mRNA expressions were negatively correlated with hepatic
      Cu concentration, while CCS (P = 0.0887) and SOD1 had a tendency (P = 0.0733) to
      be negatively correlated to hepatic Cu concentration. These data indicate that
      higher than normal hepatic Cu concentration downregulates gene expression of
      CTR1, ATP7A, ATP7B, and Cox17, which are involved in bovine liver copper
      homeostasis.

PMID- 19099206
TI  - The role of arginine-nitric oxide pathway in patients with Alzheimer disease.
AB  - There is a reciprocal regulation of arginase and nitric oxide synthase in L
      arginine-metabolizing pathways. There are various evidences of the role of nitric
      oxide in several neuropsychiatric disorders including Alzheimer's disease.
      However, there is no study that has investigated the role of arginase as an
      important part of the arginine regulatory system affecting nitric oxide synthase
      activity in Alzheimer's disease. This study aims to investigate arginase,
      manganese (a cofactor of arginase), and total nitrite levels (a metabolite of NO)
      and their relationship to the arginine-NO pathway in patients with Alzheimer's
      disease. Arginase activities, Mn, and total nitrite levels were measured in
      plasma from 47 patients with Alzheimer's disease and 43 healthy control subjects.
      Plasma arginase activities and manganese were found to be significantly lower and
      total nitrite level higher in patients with Alzheimer's disease compared with
      controls. Our results suggest that the arginine-NO pathway is involved in the
      pathogenesis of Alzheimer's disease.

PMID- 19099207
TI  - Biosafety of flavonoids in rats: effects on copper and zinc homeostasis and
      interaction with low-level pesticide exposure.
AB  - Two 30-day experiments (36 male Sprague-Dawley rats each) were conducted to
      determine effect of administering flavonoid mixture (FM) with concomitant
      exposure to a pesticide mixture (PM) or FM at varied levels on changes in
      concentrations of zinc and copper in tissues. In experiment 1, PM = chlorpyrifos,
      endosulfan, and thiram at 25% LD(50) was dissolved in soybean (SB) oil and gavage
      fed 0.1 mL 5 days/week; FM in SB oil was mixed in AIN-93M diet at 1.0 and 5.0
      mM/kg diet and fed ad libitum. The groups were Control (CON), PM, FM1, FM5,
      PM+FM1, and PM+FM5. In experiment 2, FM in 1% polyethylene glycol was gavage-fed
      (0.5 mL/5 days/week), at increasing levels(mg/kg body weight); the groups were
      CON, FM5, FM25, FM50, FM100, and FM200. In experiment 1, PM plus FM increased
      tissue Cu as compared to the CON by: plasma, 16-37%; liver, 9-20%; kidney, 13
      41%; small intestinal mucosa (IM), 41%; and small intestines (SI), 77%. In
      experiment 2, FM fed at higher levels decreased tissue Cu by: plasma, 22-36%;
      liver, 23%; kidney, 24-44%; IM, 17-26%; and SI, 58% and 77%, as compared to
      respective CON. Kidney zinc increased at higher concentrations of FM by 14-34%.
      These results indicate that flavonoids can modify copper homeostasis depending on
      whether they are fed in the diet or by gavage.

PMID- 19099208
TI  - Compactin production studies using Penicillium brevicompactum under solid-state
      fermentation conditions.
AB  - In the present study, compactin production by Penicillium brevicompactum WA 2315
      was optimized using solid-state fermentation. The initial one factor at a time
      approach resulted in improved compactin production of 905 microg gds(-1) compared
      to initial 450 microg gds(-1). Subsequently, nutritional, physiological, and
      biological parameters were screened using fractional factorial and Box-Behnken
      design. The fractional factorial design studied inoculum age, inoculum volume,
      pH, NaCl, NH(4)NO(3), MgSO(4), and KH(2)PO(4). All parameters were found to be
      significant except pH and KH(2)PO(4). The Box-Behnken design studied inoculum
      volume, inoculum age, glycerol, and NH(4)NO(3) at three different levels.
      Inoculum volume (p = 0.0013) and glycerol (p = 0.0001) were significant factors
      with greater effect on response. The interaction effects were not significant.
      The validation study using model-defined conditions resulted in an improved yield
      of 1,250 microg gds(-1) compactin. Further improvement in yield was obtained
      using fed batch mode of carbon supplementation. The feeding of glycerol (20% v/v)
      on day 3 resulted in further improved compactin yield of 1,406 microg gds(-1).
      The present study demonstrates that agro-industrial residues can be successfully
      used for compactin production, and statistical experiment designs provide an easy
      tool to improve the process conditions for secondary metabolite production.

PMID- 19099209
TI  - Construction, purification, and characterization of anti-BAFF scFv-Fc fusion
      antibody expressed in CHO/dhfr- cells.
AB  - Elevated levels of B-cell-activating factor of the tumor necrosis factor family
      (BAFF) have been implicated in the pathogenesis of autoimmune diseases in human.
      In this study, we have constructed a vector for the expression of a novel compact
      antibody composed of anti-BAFF single-chain antibody fragment (scFv) and the Fc
      region (the hinge region, CH2, and CH3 domains) of human IgG1 in Chinese hamster
      ovary cells. The scFv-Fc fusion protein, showing spontaneous Fc fragment-mediated
      homodimerization via disulfide bridges, was affinity-purified on protein A
      Sepharose from culture supernatant. The scFv-Fc antibody was demonstrated to
      retain high binding affinity to antigen and prolonged clearance time in blood and
      to possess some human IgG crystallizable fragment effector functions such as
      protein A binding and antibody-dependent cellular cytotoxicity. These results
      suggest that this recombinant antibody may have therapeutic applications in the
      therapy of autoimmune disorders mediated by BAFF.

PMID- 19099210
TI  - Co-expression of recombinant nucleoside phosphorylase from Escherichia coli and
      its application.
AB  - The genes encoding purine nucleoside phosphorylase (PNPase), uridine
      phosphorylase (UPase), and thymidine phosphorylase (TPase) from Escherichia coli
      K12 were cloned respectively into expression vector pET-11a or pET-28a. The
      recombinant plasmids were transformed into the host strain E. coli BL21(DE3) to
      construct four co-expression recombinant strains. Two of them had double
      recombinant plasmids (DUD and DAD) and the other two had tandem recombinant
      plasmid (TDU and TDA) in them. Under the repression of antibiotic, recombinant
      plasmids stably existed in host strains. Enzymes were abundantly expressed after
      induction with IPTG and large amount of target proteins were expressed in soluble
      form analyzed with SDS-PAGE. Compared with the host strain, enzyme activity of
      the recombinant strains had been notably improved. In the transglycosylation
      reaction, yield of 2,6-diaminopurine-2'-deoxyriboside (DAPdR) from 2,6
      diaminopurine (DAP) and thymidine reached 40.2% and 51.8% catalyzed by DAD and
      TDA respectively; yield of 2,6-diaminopurine riboside (DAPR) from DAP and uridine
      reached 88.2% and 58.0% catalyzed by TDU and DUD respectively.

PMID- 19099211
TI  - Incidence of coronary artery disease and necessity of revascularization in
      symptomatic patients requiring permanent pacemaker implantation.
AB  - BACKGROUND AND PURPOSE: The cause of severe cardiac conduction disturbances or
      sinus node dysfunction is often unknown. The objective of this study was to
      assess the incidence of coronary artery disease (CAD) and the necessity of
      revascularization in patients with symptomatic bradycardia requiring permanent
      pacemaker implantation and to try to find a causal association between the need
      for a pacemaker and the presence of CAD. PATIENTS AND METHODS: From January 2002
      to December 2005, 507 pacemakers were implanted due to symptomatic bradycardia.
      In the presence of at least one atherosclerotic risk factor, patients were
      recommended to undergo coronary angiography. Each patient underwent exercise or
      dobutamine echocardiography to detect myocardial ischemia. RESULTS: 212 of the
      507 patients (42%) with permanent pacemaker implantation (141 men, mean age 70 +/
      9 years) underwent coronary angiography within 2 months before or after
      pacemaker implantation. Twelve patients (6%) had a normal angiogram. No
      significant CAD was found in 37 patients (17%), and significant narrowing of the
      coronary arteries in 150 (71%). Conservative treatment was recommended in 128
      patients (60%), 40 patients (19%) were treated with percutaneous coronary
      intervention, and 44 patients (21%) underwent coronary artery bypass grafting.
      CONCLUSION: The data indicate that patients with severe conduction disturbances
      or sinus node dysfunction requiring permanent pacemaker implantation are more
      likely to have CAD with subsequent myocardial revascularization in the presence
      of at least one atherosclerotic risk factor. A causal association between the
      need for pacemaker and CAD could not be established from the results.

PMID- 19099212
TI  - [Doctor-patient communication in the cathlab. How to deliver the news].
AB  - BACKGROUND: Communication between patient and physician remains a central step of
      interaction. PATIENTS AND METHODS: 15 min after receiving the results of their
      coronary angiography via a standard verbal report, a total of 288 patients were
      asked the following questions: (1) Were the results of coronary angiography
      explained to you? (2) Who performed your procedure? (3) Were there any narrowings
      in your coronary arteries? (4) Was your left ventricular ejection fraction
      normal? (5) What kind of therapy was recommended to you? RESULTS: 98.6% of the
      patients were informed about the results of their coronary angiography. 31.2%
      were able to recall the name of the interventionalist. 52.8% knew about their
      coronary arteries, 36.8% knew their left ventricular function, and 92.7% were
      able to recall the recommendations for therapy (mean 53.4% correct answers). In
      14.6%, the causes of incorrect answers were related to the patient, in 85.4% to
      the doctor. The number of incorrect answers increased significantly in patients
      with complex angiographic results, cultural discordance between physician and
      patient, and presentation of the results by noncardiologists (p < 0.001 for all).
      CONCLUSION: Communication of coronary angiography results to patients via
      standard verbal reports leads to frequent misunderstanding. To resolve
      communication problems in the cathlab as effective as possible, communication
      skills of physicians should be improved.

PMID- 19099213
TI  - [Ethical and empirical limitations of randomized controlled trials].
AB  - In assessing the benefits of health services it is presumed that the relationship
      of cause and effect can be determined by scientific methods. In general, the
      randomized controlled trial (RCT) is considered the gold standard for the
      generation of scientific evidence. Yet there is an increasing amount of data
      indicating that not in all situations RCTs seem to be the adequate tool for
      generating evidence. In many instances, RCTs are, in fact, barely useful to
      reflect the real-world situation of health-care services. Some of the well-known
      yet mostly ignored limitations of RCTs are summarized.The absence of definite a
      priori preferences for a specific kind of intervention (equipoise) is an
      essential prerequisite for both physicians' and patients' consent to participate
      in an RCT. Numerous examples of quantitative studies confirm that the willingness
      to accept randomization is limited in operative disciplines. If it is true that
      the invasiveness of a diagnostic or therapeutic intervention correlates with the
      preferences of doctors and patients, the small number of RCTs in operative fields
      should be expected. Further development of the important concept of RCTs should
      specify the conditions under which RCTs can generate significant results. Paying
      attention to this will open up new perspectives for the assessment of health-care
      services.

PMID- 19099214
TI  - [Antibody therapy in hematology and oncology - part 1].

PMID- 19099215
TI  - [Neurology versus internal medicine: who's better in treating acute stroke?].

PMID- 19099216
TI  - [Polymyalgia rheumatica and giant cell arteritis. New aspects in diagnosis and
      treatment].

PMID- 19099217
TI  - [Women's perspective on menopausal hormone therapy: a qualitative study].

PMID- 19099218
TI  - Bioactivities of polyphenolics from the roots of Bauhinia racemosa.
AB  - Various extracts of Bauhinia racemosa Lamk. (roots) and the isolated
      polyphenolics, viz. 1,7,8,12b-tetrahydro-2,2,4-trimethyl-10-methoxy-2H-benzo
      [6,7] cyclohepta[1,2,3-de][1]benzopyran-5,9-diol (racemosol) (1), 1,7,8,12b
      tetrahydro-2,2,4-trimethyl-2H-benzo[6,7]cyclohepta[1,2,3-de][1]benzopyran-5,10,11
      triol (2), and 1,7,8,12b-tetrahydro-2,2,4-trimethyl-2H-benzo[6,7] cyclohepta
      [1,2,3-de][1]benzopyran-5,9,10-triol (de-O-methyl racemosol) (3) were screened
      for antibacterial, antifungal, and antiviral activities. The isolated compounds
      exhibited profound antibacterial and antifungal activities while methanol extract
      exhibited potential efficacy against Herpes simplex virus.

PMID- 19099219
TI  - Two novel A-seco-rearranged lanostane triterpenoids from Abies sachalinensis.
AB  - Further chemical study led to two new A-seco-rearranged lanostane triterpenoid
      derivatives (1-2) and one known compound Abiesanolide C (3) from the ethyl
      acetate (EtOAc) soluble fraction of the MeOH extract of Abies sachalinensis
      needles. The new compounds were identified as 3,4-seco-8-(14-->13R)abeo-17,13
      friedo-9beta-lanosta-4(28), 7, 14, 24-tetraen-26,23-olide-23-hydroxy-3-oic acid
      and methyl-3,4-seco-8-(14-->13R) abeo-17,13-friedo-9beta-lanosta-4(28), 7, 14, 24
      tetraen-26,23-olide-23-hydroxy-3-oate, respectively. Structural determination of
      these compounds were carried out by the spectral studies especially by the two
      digital (2D)-NMR and high-resolution (HR)-MS experiences.

PMID- 19099220
TI  - Osteogenic activities of genistein derivatives were influenced by the presence of
      prenyl group at ring A.
AB  - Our recent report indicated that the crude extract from stem bark of Erythrina
      variegata L. (Leguminosae) (EV) exerted beneficial effects against osteoporosis
      induced by estrogen deficiency in vivo. Follow-up phytochemical study has
      isolated genistein-derivatives mainly in the form of prenylgenistein from this
      extract, including 6-prenylgenistein, 8-prenylgenistein, and 6, 8
      diprenylgenistein. The present study was performed to investigate the structure
      function relationship of these compounds on osteoblastic proliferation,
      differentiation and mineralization in UMR 106 cells. Our results showed that
      genistein did not stimulate cell growth while 8-prenylgenistein promoted cell
      growth significantly by 10 approximately 23%. In contrast, the treatment by 6
      prenylgenistein for 48 h reduced UMR 106 cell proliferation when compared to
      cells treated with genistein. The proliferation of 6,8-diprenylgenistein-treated
      cells was greater than those treated by 6-prenylgenistein at all testing
      concentrations. For ALP activity, significant increase was found in cells treated
      by either 8-prenylgenistein or 6,8-diprenylgenistein for 48 h at the
      concentration of 10(-10) M. In mineralization study, the content of Ca and P in
      extracellular matrix were significantly increased in 8-prenylgenistein treated
      cells. The results showed that genistein derivatives isolated from EV
      demonstrated stimulatory effects on osteogenesis in UMR 106 cells. Based on the
      study of structure-activity relationship, it appears that prenylation at C-8, but
      not at C-6, could increase the bone-protective effect of genistein.

PMID- 19099221
TI  - CoMFA on the melanogenesis inhibitory activity of alkyl-3,4-dihydroxybenzoate, N
      alkyl-3,4-dihydroxybenzamide analogues, and prediction of higher active
      compounds.
AB  - To predict a new materials of superior melanogenesis inhibitory activities (MIA),
      the comparative molecular field analysis (CoMFA) models on MIA of alkyl-3,4
      dihydroxybenzoates and N-alkyl-3,4-dihydroxybenzamides analogues against mouse
      melanoma cell were derived and discussed quantitatively. The optimized CoMFA
      model II from the field fit alignment demonstrated better predictability of
      molecular structure with the non-cross validated conventional coefficient (r2
      (nev.)=0.984) and cross-validated coefficient (r2 (cv.) or q=0.706) than that
      from atom based fit alignment. Also, the relative contribution of the optimized
      CoMFA model II showed the steric (63.8%), electrostatic (18.4%), and hydrophobic
      (ClogP) field (17.8%), respectively. The results indicated that the esters (alkyl
      3,4-dihydroxybenzoates) are more active inhibitors than the amides (N-alkyl-3,4
      dihydroxybenzamides). Furthermore, the optimized CoMFA model II is proven to be a
      useful approach to design a highly active melanogenesis inhibitor molecules, and
      enables to predict R1 = n-dodecy and R2 = n-heptyloxy substituted compound of
      alkyl-3,4-dihydroxybenzoates as the most active compounds (Pred. pI50 = 5.87).

PMID- 19099222
TI  - Cytotoxic macrocyclic diterpenoids from Euphorbia helioscopia.
AB  - A new cytotoxic macrocyclic diterpenoid, euphornin L (1), together with seven
      known analogues were isolated from the plant Euphorbia helioscopia L. The
      structure of 1 was elucidated by spectral data and X-ray crystallographic
      analysis. Euphornin L (1) and euphoscopin F (2) exhibited significant
      cytotoxicity against HL-60 cell lines with IC(50) values of 2.7 and 9.0 microM,
      respectively. The 13C-NMR data of euphoscopin F (2), epieuphoscopin B (3),
      euphoscopin B (5), and euphoscopin C (6) were also reported for the first time.

PMID- 19099223
TI  - Inhibitory effect of hypochlorous acid on lower esophageal sphincter tone
      relaxation by vasoactive intestinal peptide.
AB  - Under physiological conditions, hypochlorous acid (HOCl) is the major product of
      myeloperoxidase, a ferric heme enzyme released in inflammatory diseases. In the
      present study, we investigated the effect of HOCl compared to hydrogen peroxide
      (H2O2) on the vasoactive intestinal polypeptide (VIP)-induced relaxation of
      feline lower esophageal sphincter (LES) strips. Isometric tension on LES strips
      was measured using a force transducer. VIP induced the relaxation of basal LES
      tone in a concentration-dependent manner. Pretreatment with HOCl (10(-4) M)
      significantly reduced the VIP-induced relaxation at smaller concentrations than
      H2O2 (10(-3) M). VIP-induced relaxation is mediated via the Gi/o protein, since
      pretreatment with Pertussis Toxin (PTX) showed an inhibitory effect on the
      relaxation. HOCl showed an additional inhibitory effect on the reduced relaxation
      by PTX, indicating that HOCl might affect another G protein as well as Gi/o.
      However, HOCl did not affect SNP-, SIN-1-, and 8-br-cGMP-induced relaxation. Nor
      did HOCl modify the relaxation induced by either forskolin or db-cAMP in LES
      muscle strips. These results suggest that during short-term treatment, HOCl may
      damage the upstream events including G protein level, and result in alteration of
      LES tone in the feline esophagus, similar to the inhibitory effects of H2O2.

PMID- 19099224
TI  - Concise synthesis of Obovatol: Chemoselective ortho-bromination of phenol and
      survey of Cu-catalyzed diaryl ether couplings.
AB  - Concise total synthesis of obovatol (1) was achieved from the commercially
      available eugenol (5) via linear 4 steps in 40% overall yield. The key features
      of the synthesis involve the chemoselective orthobromination of phenol in the
      presence of isolated double bond and the efficient Cu-catalyzed Ullmann coupling
      of two aromatic moieties for the diaryl ether skeleton.

PMID- 19099225
TI  - Anti-hyperlipidemic effect of an edible brown algae, Ecklonia stolonifera, and
      its constituents on poloxamer 407-induced hyperlipidemic and cholesterol-fed
      rats.
AB  - We conducted this study to isolate novel anti-hyperlipidemic agents derived from
      natural marine products. To accomplish this, we investigated the effects of
      ethanolic (EtOH) extracts of Ecklonia stolonifera and its phlorotannin
      constituents, eckol and dieckol, on serum lipid levels in rats with
      hyperlipidemia that was induced by a high-cholesterol diet or poloxamer 407.
      Treatment with the EtOH extracts of E. stolonifera and its phlorotannin-rich
      ethyl acetate (EtOAc) and n-butanol (n-BuOH) fractions induced a significant
      reduction in triglycerides (TG), total cholesterol (TC), and low-density
      lipoprotein-cholesterol (LDL-C) levels, as well as a significant increase in the
      high-density lipoprotein-cholesterol (HDLC) level in hyperlipidemic rats.
      However, treatment with the water (H(2)O) fraction did not exert any significant
      effects on the serum levels of hyperlipidemic rats. In addition, eckol and
      dieckol isolated from the active EtOAc fraction induced a significant reduction
      in serum TG, TC, and LDL-C levels, as well as in the atherogenic index (A.I.).
      Furthermore, treatment with dieckol induced a greater decrease in the serum TG,
      TC, and LDL-C levels of hyperlipidemic rats than eckol or lovastatin, as well as
      an increase in the serum HDL-C levels. Taken together, these results suggest that
      phlorotannins such as eckol and dieckol have the potential for use for the
      prevention of hyperlipidemic atherosclerosis.

PMID- 19099227
TI  - Triterpenoic acids of Prunella vulgaris var. lilacina and their cytotoxic
      activities in vitro.
AB  - The column chromatographic separation of the MeOH extract from the aerial parts
      of Prunella vulgaris var. lilacina Nakai led to the isolation of fifteen
      triterpenoic acids (2-6, 9-13, 16-20), four flavonoids (14, 21-23), four
      phenolics (7, 8, 15, 24), and a diterpene (1). Their structures were determined
      by spectroscopic methods to be trans-phytol (1), oleanic acid (2) ursolic acid
      (3), 2alpha,3alpha,19alpha-trihydroxyurs-12en-28oic acid (4), 2alpha,3alpha
      dihydroxyurs-12en-28oic acid (5), maslinic acid (6), caffeic acid (7), phydroxy
      cinnamic acid (8), 2alpha,3alpha,19alpha,23-tetrahydroxyurs-12en-28oic acid (9),
      2alpha,3alpha,23-trihydroxyurs-12en-28oic acid (10), 2alpha,3beta-dihydroxyurs
      12en-28oic acid (11), 2alpha,3beta,24-trihydroxyolea-12en-28oic acid (12), (12R,
      13S)-2alpha,3alpha,24,trihydroxy-12,13-cyclo-taraxer-14-en-28oic acid (13),
      quercertin 3-O-beta-D-glucopyranoside (14), rosmarinic acid (15),
      2alpha,3alpha,24-trihydroxyurs-12,20(30)-dien-28oic acid (16), 2alpha,3alpha,24
      trihydroxyolea-12en-28oic acid (17), 2alpha,3beta,19alpha,24-tetrahydroxyurs-12en
      28oic acid 28-O-Dglucopyranoside (18), 2alpha,3alpha,19alpha,24-tetrahydroxyurs
      12en-28oic acid 28-O-D-glucopyranoside (19), prunvuloside A (20), kaempferol 3-O
      alpha-L-rhamnopyranosyl(1-->6)-beta-D-glucopranoside (21), kaempferol 3-O-beta-D
      glucopyranoside (22), quercertin 3-O-alpha-L-rhamnopyranosyl(1-->6)-beta-D
      glucopyranoside (23), and 2-hydroxy-3-(3',4'-dihydroxyphenly)propanoic acid (24).
      Compounds 1, 8-12, 17, 21, 23, and 24 were isolated from this plant source for
      the first time. The isolated compounds were evaluated for their cytotoxicity
      against A549, SK-OV-3, SK-MEL-2, and HCT15 cells in vitro using the sulforhodamin
      B bioassay (SRB) method. Compound 3 exhibited moderate cytotoxic activity against
      A549, SK-OV-3, SK-MEL-2, and HCT15 cells, with ED(50) values of 3.71, 3.65,
      13.62, and 5.44 microM, respectively.

PMID- 19099226
TI  - Antitumor and antioxidant activity of protocatechualdehyde produced from
      Streptomyces lincolnensis M-20.
AB  - We characterized the biological functions of protocatechualdehyde (PA) isolated
      from the butanol extract of culture supernatant from Streptomyces lincolnensis M
      20. Following butanol extraction, it was purified by silica gel and Sephadex LH
      20 column chromatography. PA was analyzed by Furier Transform Infrared
      Spectroscopy (FT-IR), Gas chromatograph-Mass Spectrometer (GC-MS), and Nuclear
      Magnetic Resonance (NMR). PA had potent antioxidant activity, as measured by 1,1
      diphenyl-2-picrylhydrazyl (DPPH) radical scavenging activity. Antitumor activity
      against MCF-7 human breast cancer cells was evaluated by the 3-(4,5
      dimethylthazol-2-yl)-2,5-diphenyl tetrazolium-bromide (MTT) assay. PA treatment
      (0 approximately 150 muM) dose-dependently blocked apoptosis, as shown by
      improved cell viability and inter-nucleosomal DNA fragmentation. Our findings
      suggest that Streptomyces lincolnensis M-20, a lincomycin producer, also produces
      protocatechualdehyde.

PMID- 19099228
TI  - Four-week administration of nimesulide, a cyclooxygenase-2 inhibitor, improves
      endothelial dysfunction in the hindlimb vasculature of streptozotocin-induced
      diabetic rats.
AB  - The aim of this study was to examine the effect of chronic administration of
      nimesulide, a cyclooxygenase-2 inhibitor, on endothelial dysfunction in
      streptozotocin-induced diabetic rats. Three groups of Sprague-Dawley rats (300
      350 g, n=6) were used. The first group served as normoglycemic control and the
      second and third groups were rendered diabetic by an intraperitoneal injection of
      streptozotocin (60 mg/kg). The third group received the selective COX-2
      inhibitor, nimesulide (20 mg/kg/day), orally by gavage for 4 weeks while the
      second group received only drinking water and served as diabetic control. At the
      end of the treatment period, the rats were anesthetized with urethane (1.2 g/kg)
      and mean arterial pressure, heart rate and hindlimb blood flow were monitored.
      This was followed by the injection of acetylcholine (endothelium-dependent
      vasodilator, 0.1-0.8 microg/kg) and sodium nitroprusside (endothelium-independent
      vasodilator 1-4 microg/kg). Mean arterial pressure was significantly reduced and
      hindlimb vascular conductance was not significantly affected in the control
      diabetic group when compared to the normoglycemic control group. Nimesulide
      treatment did not cause any significant change in any of the measured hemodynamic
      parameters. Acetylcholine and sodium nitroprusside induced dose-dependent
      increases in hindlimb vascular conductance in control normoglycemic rats which
      were attenuated in diabetic control rats. Nimesulide reversed the attenuation of
      acetylcholine-induced increase in hindlimb vascular conductance. In conclusion,
      chronic administration of the selective COX-2 inhibitor, nimesulide improved
      endothelial dysfunction in the hindlimb vasculature of streptozotocin induced
      diabetic rats. This suggests that COX-2 products might be involved in the
      pathogenesis of endothelial dysfunction in streptozotocin-induced diabetic rats.

PMID- 19099229
TI  - Inhibitory effect of kefiran on ovalbumin-induced lung inflammation in a murine
      model of asthma.
AB  - Kefiran is a major component of kefir which is a microbial symbiont mixture that
      produces jelly-like grains. This study aimed to evaluate the therapeutic
      availability of kefiran on the ovalbumin-induced asthma mouse model in which
      airway inflammation and airway hyper-responsiveness were found in the lung.
      BALB/c mice sensitized and challenged to ovalbumin were treated intra-gastrically
      with kefiran 1 hour before the ovalbumin challenge. Kefiran significantly
      suppressed ovalbumin-induced airway hyper-responsiveness (AHR) to inhaled
      methacholine. Administration of kefiran significantly inhibited the release of
      both eosinophils and other inflammatory cells into bronchoalveolar lavage (BAL)
      fluid and lung tissue which was measured by Diff-Quik. Interleukin-4 (IL-4) and
      interleukin-5 (IL-5) were also reduced to normal levels after administration of
      kefiran in BAL fluid. Histological studies demonstrate that kefiran substantially
      inhibited ovalbumin-induced eosinophilia in lung tissue by H&E staining and
      goblet cell hyperplasia in the airway by PAS staining. Taken above data, kefiran
      may be useful for the treatment of inflammation of lung tissue and airway hyper
      responsiveness in a murine model and may have therapeutic potential for the
      treatment of allergic bronchial asthma.

PMID- 19099230
TI  - Anti-allergic activity of an ethanol extract from Salviae miltiorrhiza.
AB  - As part of an ongoing investigation aimed at the discovery of novel bioactive
      medicinal herbs with anti-inflammatory properties, the effects of an ethanolic
      extract from the parts of Salviae miltiorrhiza Bunge (ESM) were evaluated using
      in vitro and in vivo animal model analysis. ESM inhibited cyclooxygenase-2 (COX
      2) and COX-1-dependent phases of prostaglandin D2 (PGD2) generation in bone
      marrow-derived mast cells (BMMC) in a concentration-dependent manner with IC50
      values of 3.96 microg/mL and 21.54 microg/mL, respectively. Furthermore, ESM
      inhibited leukotriene C4 (LTC4) production with an IC50 value of 2.6 microg/mL.
      These results clearly demonstrated the dual COX-2 selective/5-lipoxygenase
      inhibitory activity that ESM possessed. ESM strongly inhibited a degranulation
      reaction in a dose dependent manner within a BMMC system, with an IC50 value of
      22.4 microg/mL. Additionally, ESM was tested in a rat passive cutaneous
      anaphylaxis (PCA) reaction assay by oral administration (25 to 100 mg/kg). ESM
      dose-dependently inhibited the PCA reaction, which was activated by anti
      dinirophenyl (DNP) IgE. These results suggested that ESM might be beneficial in
      regulating various allergic reactions.

PMID- 19099231
TI  - Phenethyl isothiocyanate induced apoptosis via down regulation of Bcl-2/XIAP and
      triggering of the mitochondrial pathway in MCF-7 cells.
AB  - Although isothiocyanates have been shown to inhibit carcinogen-induced
      tumorigenesis, no studies have been made to determine their therapeutic potential
      for the treatment of breast cancer. In the present study, we evaluated the
      apoptotic activities of phenethyl isothiocyanate (PEITC) in human breast cancer
      MCF-7 cells. Exposure to PEITC potently reduced cell viability. In addition, DNA
      fragments and TUNEL positive nuclei were detected in PEITC-treated cells.
      Furthermore, PEITC induced apoptosis via activation of caspases 7 and 9 and the
      cleavage of PARP, and these effects were reversed by treatment with the caspase
      inhibitor, Z-VAD-fmk. PEITC also caused a decrease in the levels of Bcl-2 with a
      concomitant increase in Bax levels, which resulted in the release of cytochrome
      c. XIAP suppression and Smac translocation also contributed to the PEITC-induced
      apoptosis. However, PEITC did not increase the expressions of p53 and p21. Taken
      together, the results of this study demonstrate that PEITC significantly induces
      apoptosis via a mitochondrial pathway. Specifically, PEITC induced a change in
      the Bax/Bcl-2 ratios, XIAP levels and Smac translocation that was conjunction
      with the release of cytochrome c and following caspase activation. Therefore,
      PEITC has the potential for use as a therapeutic agent for the treatment of
      breast cancer.

PMID- 19099232
TI  - Transport of mistletoe lectin by M cells in human intestinal follicle-associated
      epithelium (FAE) in vitro.
AB  - Purified mistletoe lectins are known to have cytotoxic and stimulating activities
      in the immune system. Mistletoe extract has been given subcutaneously because of
      its unstablity and poor absorption in the Gastrointestinal (GI) tract. A hallmark
      of M cells is their capacity to internalize material from the lumen and to
      transfer it efficiently to the underlying lymphoid cells. Although lectins are
      the prime candidates for oral vaccine delivery, the mechanisms whereby lectins
      are taken up, transported by M cells, and affect underlying immune cells remain
      poorly understood. In this study, uptake mechanism of Korean mistletoe lectin
      (Viscum album L. var. coloratum aggulutinin, VCA) across the human FAE (follicle
      associated epithelium) was investigated. An inverted FAE model of co-culture was
      obtained by a co-culture system of Caco-2 cells and human Raji B lymphocytes, and
      VCA transport across the in vitro model of human FAE was investigated. There was
      a greater transport of VCA across FAE monolayer cells than that of Caco-2
      monolayer cells. These observations will be useful to assess the transport of
      other orally administered material in the GI tract.

PMID- 19099233
TI  - Determination of propylthiouracil in pharmaceutical formulation by high
      performance liquid-chromatography with a post-column iodine-azide reaction as a
      detection system.
AB  - A high-performance liquid chromatographic method with a post-column iodine-azide
      reaction has been chosen and tested for validity in quantitative determination of
      propylthiouracil in tablets. A mobile phase with a flow rate of 1.4 ml/min was
      conducted in the form of isocratic chromatography on a C18 column with
      acetonitrile-water-sodium azide solution (2.5%; pH 5.5) 24:26:50 (v/v/v).
      Unreacted iodine from post-column iodine-azide induced by reaction was monitored
      with visible detection at lambda=350 nm. The method proved both its linearity
      within the range of 8-100 nM (r2>0.9988) and satisfactory results of inter-day
      precision (RSD<4.2%) and accuracy (recovery>91%). The limits of detection (DDL)
      and quantification (DQL) reached the levels of 5 and 8 nM, respectively. The
      validation of the method comprised also its specificity. The results obtained
      proved the suitability and appropriateness of the suggested method for intended
      use.

PMID- 19099234
TI  - Enhanced tamoxifen bioavailability after oral administration of tamoxifen in rats
      pretreated with naringin.
AB  - The aim of this study was to investigate the effect of naringin on the
      bioavailability and pharmacokinetics of tamoxifen and of its metabolite, 4
      hydroxytamoxifen in rats. The pharmacokinetic parameters of tamoxifen and 4
      hydroxytamoxifen were determined by HPLC after pretreating with naringin (1.5,
      7.5, and 15 mg/kg) 30 min before orally administering tamoxifen (10 mg/kg).
      Compared with the control group (treated with tamoxifen alone), naringin
      pretreated animals showed significantly (p<0.01) increased areas under the plasma
      concentration-time curves (AUC) and peak tamoxifen concentrations (Cmax). The
      absolute bioavailabilities (AB%) of tamoxifen in naringin pretreated animals were
      enhanced versus control (from 32.8% to 47.1%), and the relative bioavailabilities
      (RB%) of tamoxifen in the naringin pretreated groups were 2.02-2.88 times higher
      than that in the control. No significant changes in the terminal half-life
      (t(1/2)) or Tmax of tamoxifen were observed in the naringin pretreated groups.
      The AUCs of 4-hydroxytamoxifen after pretreating naringin were also significantly
      elevated (p<0.05) versus the control. But metabolite ratios (MR; AUC of 4
      hydroxytamoxifen to tamoxifen) were significantly lower. These results suggest
      that the enhanced bioavailability of tamoxifen in the presence of naringin might
      be due to the inhibition of CYP3A4 by naringin. If the results of this study are
      further confirmed by clinical trials, tamoxifen dosages should be adjusted to
      avoid potential drug interaction when tamoxifen is used clinically in combination
      with naringin-containing dietary supplements.

PMID- 19099235
TI  - Formulation of a extended release tablet containing dexibuprofen.
AB  - Dexibuprofen, or S(+)-ibuprofen, is the pharmacologically effective enantiomer of
      racemic ibuprofen. Since dexibuprofen has a low melting point, the amorphous form
      having a high melting point was prepared with the fused solid dispersion method.
      With the fused solid dispersion of dexibuprofen, immediate release tablets,
      extended release tablets, and dual release tablets were compressed and their
      dissolution profiles compared. The dissolution profiles of the extended release
      and the dual release tablet depended on the amount of used release modulators
      (PEO 5,000,000). The release profiles of extended release tablets and extended
      release part of dual release tablets were well fitted to zero-order release
      model. The correlation coefficient ranged from 0.982 to 0.995. A pharmacokinetic
      evaluation where healthy volunteers took tablets of DRT-1 (300 mg) once and the
      reference drug, two tablets of conventional immediate release tablet (Daxfen, 300
      mg), with a 6-h interval between them was studied. The 90% confidence interval
      for the ratio of the logarithmically transformed AUC (0-24 h), Cmax (0-6 h), and
      Cmax (6-24 h) values of the dual release tablet compared to those of the
      conventional immediate release tablet were calculated to be between 0.9176 and
      1.0007, 0.9240 and 1.1968, and 0.8713 and 1.1414, respectively. When the
      immediate release tablet was taken two times with a six hour interval between
      doses it showed a bioequivalent effect to taking the dual release tablet once
      within 12 h. The Cmax was reached due to the rapid absorption of the immediate
      release portion of the dual release tablet and the AUC was maintained due to
      continuous absorption of the extended release portion.

PMID- 19099236
TI  - Simultaneous determination of methamphetamine, 3,4-methylenedioxy-N
      methylamphetamine, 3,4-methylenedioxy-N-ethylamphetamine, N,N
      dimethylamphetamine, and their metabolites in urine by liquid chromatography
      electrospray ionization-tandem mass spectrometry.
AB  - A liquid chromatography-electrospray ionization-tandem mass spectrometric (LC-ESI
      MS/MS) method was developed and validated for the simultaneous detection and
      quantification of seven amphetamine derivatives (amphetamine (AP),
      methamphetamine (MA), 3,4-methylenedioxy-N-amphetamine (MDA), 3,4-methylenedioxy
      N-methamphetamine (MDMA), 3,4-methylenedioxy-N-ethylamphetamine (MDEA), N,N
      dimethylamphetamine (DMA), and N,N-dimethylamphetamine-N-oxide (DMANO)) in human
      urine. Seven deuterium-labeled compounds were prepared for use as internal
      standards to quantify the analytes. One milliliter of urine was combined with 1
      mL of 0.2 M sodium carbonate buffer solution (pH 9.0) before solid phase
      extraction (SPE). An Oasis HLB SPE column followed by chromatographic separation
      on a Capcell Pak C18 MG-II column (150 x 2.0 mm I.D., 5 microm) and electrospray
      mass spectrometry with multiple reaction monitoring were used for selective and
      sensitive detection. The use of ammonium formate (5 mM, pH adjusted to 4.0 with
      formic acid, Solvent A) and acetonitrile (Solvent B) as the mobile phase at a
      flow rate of 230 microL/min was found to be the most effective for the
      separation. The linear ranges were 5.0-1000 ng/mL for AP, MDA, MDMA, MDEA, DMA,
      and DMANO and 10.0-1000 ng/mL for MA, with good correlation coefficients (r2 >
      0.996). The intra-day, inter-day, and interperson precisions were within 14.6%,
      12.1% and 15.5%, respectively. The intra-day, inter-day, and interperson
      accuracies were between -11.6 and 9.0%, -7.9 and 2.3%, and -13.2 and 4.3%,
      respectively. The limits of detection (LODs) for each analytical compound were
      lower than 1.95 ng/mL. The recovery ranged from 72.3 to 103.3%. The applicability
      of the developed method was examined by analyzing several urine samples from
      confirmed drug abusers.

PMID- 19099237
TI  - Skin penetration and retention of L-ascorbic acid 2-phosphate using multilamellar
      vesicles.
AB  - Transdermal formulation of L-ascorbic acid 2-phosphate magnesium salt (A2P) was
      prepared using multilamellar vesicles (MLV). A2P was either physically mixed with
      or entrapped into three different MLVs of neutral, cationic, and anionic liposome
      vesicles. For the preparation of neutral MLVs, phosphatidylcholine (PC) and
      cholesterol (CH) were used. For cationic and anionic MLVs, dioleoyl
      trimethylammonium-propane and dimyristoyl glycerophosphate were added as surface
      charge inducers, respectively, in addition to PC and CH. Particle size of the
      three A2P-loaded MLVs was submicron, and polydispersity index revealed homogenous
      distribution of the prepared MLVs except neutral ones. Skin penetration study
      with hairless mouse skin showed that both physical mixtures of A2P with empty
      MLVs and A2P-loaded MLVs increased penetration of the drug compared to aqueous
      A2P solution. During the penetration, however, significant amount of the drug was
      metabolized into L-ascorbic acid, which has no beneficial effect on stimulation
      of hair growth. Out of the physical mixtures and A2P-loaded MLVs tested, physical
      mixture of A2P with empty cationic MLV resulted in the greatest skin penetration
      and retention in hairless mouse skin.

PMID- 19099238
TI  - Selective solid-phase extraction of ethynylestradiol from river water by
      molecularly imprinted polymer microcolumns.
AB  - A selective on-column molecularly imprinted solid-phase extraction (MISPE) for
      ethynylestradiol (EE2) from water samples was developed. Following a non-covalent
      molecular imprinting approach, two molecularly imprinted polymers (MIPs) have
      been synthesised using methacrylic acid (MAA) as functional monomer,
      ethyleneglycol dimethacrylate (EGDMA) as crosslinker and EE2 as template, in two
      different polymerisation solvents (acetonitrile or toluene). The optimisation of
      the on-column MISPE conditions for the selective rebinding of the EE2 resulted in
      a flow rate of 2.3 mL min(-1) and volumes of 1 mL toluene and 1.5 mL methanol
      acetic acid (9:1) for washing and elution steps, respectively. The selectivity of
      the imprinted polymer towards several related estrogens such as estriol (E3),
      estrone (E1) and estradiol (E2) was evaluated. The recovery of EE2 from a 50-mL
      spiked river-water sample was 75% when the optimised on-column MISPE was applied.

PMID- 19099239
TI  - Highly sensitive sensor for detection of NADH based on catalytic growth of Au
      nanoparticles on glassy carbon electrode.
AB  - In this work, an electrochemical dihydronicotinamide adenine dinucleotide (NADH)
      sensor based on the catalytic growth of Au nanoparticles (Au NPs) on glassy
      carbon electrode was developed. Catalyzed by Au NPs immobilized on pretreated
      glassy carbon electrode, the reduction of AuCl(4)(-) in the presence of
      hydroquinone and cetyltrimethyl ammonium chloride led to the formation of
      enlarged Au NPs on the electrode surface. Spectrophotometry and high-resolution
      scanning electronic microscope (SEM) analysis of the sensor morphologies before
      and after biocatalytic reaction revealed a diameter growth of the nanoparticles.
      The catalytic growth of Au NPs on electrode surface remarkably facilitated the
      electron transfer and improved the performance of the sensor. Under optimal
      conditions, NADH could be detected in the range from 1.25 x 10(-6) to 3.08 x 10(
      4) M, and the detection limit was 2.5 x 10(-7) M. The advantages of the proposed
      sensor, such as high precision and sensitivity, fast response, low cost, and good
      storage stability, made it suitable for on-line detection of NADH in complex
      biological systems and contaminant degradation processes.

PMID- 19099240
TI  - Cholecystokinin secretion induced by beta-conglycinin peptone depends on Galphaq
      mediated pathways in enteroendocrine cells.
AB  - BACKGROUND: Intraduodenal administration of peptone prepared from soybean beta
      conglycinin (BconP) stimulates cholecystokinin (CCK) secretion from
      enteroendocrine cells, and suppresses food intake in rats. However, the sensing
      mechanism of BconP by CCK-producing cells is unknown. AIM OF THE STUDY: We
      investigated signal transduction pathways mediating CCK secretion in response to
      BconP in the murine CCK-producing cell line, STC-1. METHODS: STC-1 cells were
      seeded in 48-well culture plates until sub-confluent and CCK secretion was
      examined under various conditions. CCK concentration was determined by the enzyme
      immunoassay. RESULTS: BconP dose-dependently induced CCK secretion in STC-1
      cells. Treatment with BAPTA-AM, an intracellular Ca2+ chelator, reduced BconP
      induced CCK secretion, however, removal of extracellular Ca2+ did not affect the
      secretory response. Treatment with 2-amino borate (2-APB) reduced CCK releasing
      responses, suggesting the involvement of IP(3). In addition, BconP failed to
      induce CCK secretion after treatment with the Galphaq protein inhibitor (YM
      254890). CONCLUSION: These results indicate that Galphaq pathway is responsible
      for BconP-induced CCK secretion in STC-1 cells, and suggest the involvement of a
      Galphaq-coupled GPCR(s) in dietary peptide sensing in enteroendocrine cells.

PMID- 19099242
TI  - The canonical Wnt/beta-catenin signalling pathway.
AB  - Embryonic development of multicellular organisms is an incredibly complex process
      that relies heavily on evolutionarily conserved signalling pathways to provide
      crucial cell-cell communication. Typically, secreted signalling proteins such as
      Wnts, BMPs, and Hedgehogs released by one cell population will trigger
      concentration-dependent responses in other cells located some distance away. In
      adults, the same signalling pathways orchestrate tissue renewal in organs such as
      the intestine and skin, and direct tissue regeneration in many organs following
      injury. Strict regulation of these signalling pathways is critical, with
      insufficient or excess activity having catastrophic consequences including severe
      developmental defects or, later in life, cancer. This chapter deals with the beta
      catenin-dependent branch of Wnt signalling (also referred to the canonical
      pathway).

PMID- 19099241
TI  - Evidence that a maternal "junk food" diet during pregnancy and lactation can
      reduce muscle force in offspring.
AB  - BACKGROUND: Obesity is a multi-factorial condition generally attributed to an
      unbalanced diet and lack of exercise. Recent evidence suggests that maternal
      malnutrition during pregnancy and lactation can also contribute to the
      development of obesity in offspring. We have developed an animal model in rats to
      examine the effects of maternal overeating on a westernized "junk food" diet
      using palatable processed foods rich in fat, sugar and salt designed for human
      consumption. Using this model, we have shown that such a maternal diet can
      promote overeating and a greater preference for junk food in offspring at the end
      of adolescence. The maternal junk food diet also promoted adiposity and muscle
      atrophy at weaning. Impaired muscle development may permanently affect the
      function of this tissue including its ability to generate force. AIMS: The aim of
      this study is to determine whether a maternal junk food diet can impair muscle
      force generation in offspring. METHODS: Twitch and tetanic tensions were measured
      in offspring fed either chow alone (C) or with a junk food diet (J) during
      gestation, lactation and/or post-weaning up to the end of adolescence such that
      three groups of offspring were used, namely the CCC, JJC and JJJ groups. RESULTS:
      We show that adult offspring from mothers fed the junk food diet in pregnancy and
      lactation display reduced muscle force (both specific twitch and tetanic
      tensions) regardless of the post-weaning diet compared with offspring from
      mothers fed a balanced diet. CONCLUSIONS: Maternal malnutrition can influence
      muscle force production in offspring which may affect an individual's ability to
      exercise and thereby combat obesity.

PMID- 19099243
TI  - Isolation and application of bioactive Wnt proteins.
AB  - Wnt proteins and their signaling cascades are involved in a wide variety of
      developmental processes, and deregulation of this pathway is frequently
      associated with tumorigenesis. Unlike many other growth factors, Wnts long eluded
      biochemical purification, in large part because of their hydrophobic nature,
      which is imparted by one or more lipid modifications. Here I describe a complete
      protocol that outlines the purification process for Wnt proteins. While this
      protocol has not been applied to all known Wnt proteins, it has been successfully
      applied to the purification of a large subset of Wnts, including the very
      divergent Wnt protein, Drosophila Wnt8 (Dwnt8 or WntD), indicating that this
      protocol is likely applicable to all Wnts.

PMID- 19099244
TI  - Purification and Wnt-inhibitory activities of secreted frizzled-related proteins.
AB  - Recombinant expression of secreted Frizzled-related proteins (sFRPs) in mammalian
      expression systems is a convenient source of these proteins for biological
      studies. Yields of protein vary; screening of clonal lines for high expression is
      usually worthwhile. Heparin affinity chromatography is an easy step that provides
      a major enrichment, particularly for sFRP-1 and sFRP-2. Alternatively, sFRP
      derivatives tagged with poly-histidine at their carboxyl termini are functional
      and can be readily isolated by chelating chromatography. Once purified, the
      proteins are stable indefinitely if stored frozen and they tolerate multiple
      rounds of freeze-thawing. Pre-incubation of Wnt samples with sFRP protein for 30
      min at 37 degrees C is sufficient to inhibit Wnt activity in various assays. The
      concentration of sFRP required to block Wnt signaling should be determined
      empirically, as it will vary with the Wnt preparation and cellular context.

PMID- 19099245
TI  - Measuring GSK3 expression and activity in cells.
AB  - Glycogen synthase kinase (GSK)-3 is a key signalling intermediate in the action
      ofWnts. This protein kinase is ubiquitously expressed and has high inherent
      activity but is inhibited by activation of Wnt signalling or activation of growth
      factor receptor tyrosine kinases (e.g. insulin, nerve growth factor [NGF],
      platelet-derived growth factor [PDGF], etc.). The degree of inhibition of GSK3 in
      cells treated with such reagents is dependent on the cell type and the stimulus
      used. Therefore, the ability to accurately measure GSK3 activity in cells is an
      important aspect of GSK3 research. The activity of GSK3 is reduced by
      posttranslational modification (phosphorylation) and this can be measured by
      immunoblot with specific reagents (indirect), or by immunoprecipitation and assay
      (direct), as long as the modification is protected during these procedures.
      However, inhibition by phosphorylation is specific to cellular activation by
      growth factors and nutrients. Wnt inhibition of GSK3 does not involve
      phosphorylation of these residues on GSK3 and therefore it cannot be measured
      using this modification. Currently, the simplest way to assess Wnt inhibition of
      GSK3 is to monitor phosphorylation of specific GSK3 substrates in cells (e.g.
      beta-catenin). Alternatively, Wnt inhibition of GSK3 can be measured by partial
      purification of cellular GSK3 by ion exchange chromatography and assay of
      fractions or possibly by immunoprecipitation and assay. In this chapter, we
      demonstrate the use of the different approaches to measure GSK3 activity in SH
      SY5Y cells, describe the best antibodies currently available, and discuss the
      potential drawbacks of each method.

PMID- 19099246
TI  - Inhibition of glycogen synthase kinase-3.
AB  - There are two homologous forms of glycogen synthase kinase (GSK)-3, GSK-3alpha
      and GSK-3beta, which play overlapping roles in the regulation of Wnt, Hedgehog,
      and insulin pathways, as well as the activation of nuclear factor (NF)-kappaB
      mediated gene transcription. These signaling pathways regulate gene
      transcription, cell cycle, apoptosis, inflammation, glucose metabolism, stem-cell
      renewal, and differentiation. More than 50 GSK-3 inhibitors representing a wide
      range of chemical structures have already been identified, and their utility in
      the treatment of type II diabetes mellitus, Alzheimer's disease, bipolar
      diseases, cancer, and other human pathologies is currently being investigated.
      Here, we discuss two methods of GSK-3 inhibition, which can be used to determine
      the involvement of GSK-3 in a cellular process of interest.

PMID- 19099247
TI  - Detection of cytoplasmic and nuclear localization of adenomatous polyposis coli
      (APC) protein in cells.
AB  - The adenomatous polyposis coli (APC) tumour suppressor gene is mutated in the
      majority of colon cancers. APC is a multi-domain protein whose distribution at
      different subcellular locations correlates with unique cellular processes. Our
      laboratory has focused on the link between APC subcellular location and function,
      and has characterized pathways for the trafficking of APC both into and out of
      the nucleus. Antibody specificity is an important factor in the determination of
      APC localization, and in this chapter we outline a strategy for the unambiguous
      detection of APC using a combination of biochemical and cell biology approaches.

PMID- 19099248
TI  - Detection of beta-catenin localization by immunohistochemistry.
AB  - Beta-catenin is a widely expressed 90-kDa protein with dual functions in cell
      adhesion and Wnt signalling. At the membrane, beta-catenin forms complexes with E
      cadherin to generate cell adhesion complexes responsible for maintaining the
      structural integrity of many epithelial tissues. On the other hand, accumulation
      of beta-catenin in the nucleus in response to Wnt signalling facilitates complex
      formation with Tcf transcription factors, leading to activation of a genetic
      program influencing a range of cellular processes including cell growth, cell
      movement, and cell fate. Chronic activation of the Wnt signalling pathway as a
      result of mutations in key pathway components, including beta-catenin itself, is
      a major cause of cancer. The associated increase in nuclear beta-catenin protein
      is therefore considered to be a hallmark of Wnt-driven cancers and an invaluable
      tool to detect active Wnt signalling.

PMID- 19099249
TI  - Assaying beta-catenin/TCF transcription with beta-catenin/TCF transcription-based
      reporter constructs.
AB  - Transcription-based reporters have been instrumental in characterizing the
      Wnt/beta-catenin signaling pathway and will be essential in the search for
      therapeutics aimed at combating diseases linked to aberrant signaling. In this
      chapter, we introduce a new improved Wnt/beta-catenin reporter system, beta
      catenin-activated reporter (BAR), and its accompanying control reporter system,
      found unresponsive BAR (fuBAR). Its enhanced sensitivity, increased dynamic
      range, and lentiviral platform provide a reporter system that will keep pace with
      the needs of scientists in the field.

PMID- 19099250
TI  - Native promoter reporters validate transcriptional targets.
AB  - The transcriptional activator beta-catenin is the key mediator of the canonical
      Wnt signaling pathway. However, beta-catenin does not itself bind DNA, but
      functions via interaction with T-cell factor (TCF)/ lymphoid-enhancing factor
      (LEF) transcription factors. These proteins contain a high-mobility group (HMG)
      box that binds DNA in a sequence-specific manner. Thus, in the case of active Wnt
      signaling, beta-catenin activates, in cooperation with proteins of the TCF/LEF
      family, the expression of a wide variety of genes. To date, the list of
      established Wnt targets is far from complete. The establishment of plasmids
      harbouring reporter genes under control of the native promoter sequences provides
      a tool to validate novel putative Wnt targets by directly quantifying the beta
      catenin-dependent activation of each specific gene. In this chapter, we describe
      how to generate such reporter plasmids using the MMP7 promoter as an example.

PMID- 19099251
TI  - Beta-catenin-independent Wnt pathways: signals, core proteins, and effectors.
AB  - Wnt signaling activates several distinct intracellular pathways, which are
      important for cell proliferation, differentiation, and polarity. Wnt proteins are
      secreted molecules that typically signal across the membrane via interaction with
      the transmembrane receptor Frizzled. Following interaction with Frizzled, the
      downstream effect of the most widely studied Wnt pathway is stabilization and
      nuclear translocation of the cytosolic protein, beta-catenin. In this chapter, we
      discuss two beta-catenin-independent branches of Wnt signaling: 1) Wnt/planar
      cell polarity (PCP), a Wnt pathway that signals through the small GTPases, Rho
      and Rac, to promote changes in the actin cytoskeleton, and 2) Wnt/Ca2+, a Wnt
      pathway that promotes intracellular calcium transients and negatively regulates
      the Wnt/beta-catenin pathway. Finally, during the course of our discussion, we
      highlight areas that require future research.

PMID- 19099252
TI  - Image analysis of calcium release dynamics.
AB  - Many aspects of animal development are dependent on the dynamic release of
      calcium (Ca2+) ions. Although Ca2+ release within a cell is tightly controlled,
      how the release dynamics result in a specific biological output in embryonic
      development is less clear. The integration of pharmacological and molecular
      genetic studies with in vivo imaging in zebrafish and Xenopus has linked
      endogenous Ca2+ release to the Wnt signaling network. Our data suggests that
      distinct Ca2+ release dynamics lead to antagonism of the developmentally
      important Wnt/beta-catenin pathway while sustained Ca2+ release modulates
      polarized cell movements.

PMID- 19099253
TI  - Detecting PKC phosphorylation as part of the Wnt/calcium pathway in cutaneous
      melanoma.
AB  - Signaling networks play crucial roles in the changes leading to malignancy. In
      melanoma, increased Wnt5A expression increases melanoma cell motility via
      activation of protein kinase C (PKC). PKC isoforms comprise a family
      ofserine/threonine kinases that are involved in the transduction of signals for
      cell proliferation, differentiation, and metastasis. The important role of PKC in
      processes leading to carcinogenesis and tumor cell invasion would render PKC a
      suitable target for cancer therapy, if not for its ubiquitous nature. Thus,
      targeting pathways leading to PKC activation that are more tumor specific, such
      as the non-canonical Wnt pathway, may prove to be the key to targeting PKC in
      cancer. Here we summarize the current understanding of the Wnt/calcium pathway
      and discuss methods of detecting activated/phosphorylated PKC as a result of Wnt
      signaling in malignant melanoma. We have shown that overexpression of Wnt5A
      results in the activation of PKC, while inhibition of Wnt5A via small interfering
      RNA (siRNA) treatment results in its inactivation. In addition, the use of PKC
      activators and inhibitors has allowed us to study Wnt5A effects on downstream
      genes that may prove to be key targets for molecular therapy.

PMID- 19099254
TI  - Measuring CamKII activity in Xenopus embryos as a read-out for non-canonical Wnt
      signaling.
AB  - It has been known for quite some time that not all members of the Wnt family
      induce the formation of a secondary body axis when ectopically expressed in
      Xenopus embryos. An ingenious hypothesis led to the discovery that some Wnt
      ligands have the capacity to elicit intracellular Ca2+ signaling. This finding
      has been studied in more detail in the past years, which has revealed an
      intriguing complexity of Wnt signaling. The significance of a Wnt-induced Ca(2+)
      mediated pathway during development has been demonstrated in various model
      systems so far and includes processes such as dorsal-ventral patterning,
      regulation of the canonical Wnt/beta-catenin signaling pathway, tumor formation,
      bone formation, and regulation of epithelial-mesenchymal transitions. Here we
      describe two assays to measure the activation of the Ca2+/calmodulin-dependent
      kinase (CamK)-II, a Ca(2+)-sensitive molecule described as a mediator of a non
      canonical Wnt signaling pathway.

PMID- 19099255
TI  - Analysis of Wnt7a-stimulated JNK activity and cJun phosphorylation in non-small
      cell lung cancer cells.
AB  - The cJun N-terminal kinases (JNKs) are activated in response to diverse growth
      factors and morphogens, including specific Wnt proteins. Genetic approaches have
      defined key roles for the JNKs as mediators of the Wnt-regulated epithelial cell
      programs including planar cell polarity and convergent extension. Moreover, our
      recent studies demonstrate that the JNK pathway is activated by Wnt-7a and Fzd9
      to promote an epithelial differentiation program in lung cancer cells. In
      comparison to cell stresses such as hypertonicity or ultraviolet irradiation,
      which strongly activate JNKs, morphogens and growth factors induce activation of
      the pathway that is more modest and that may be difficult to assess by
      immunoblotting approaches with anti-phospho-JNK antibodies. We find that the
      tight binding of JNKs by their substrate, cJun, provides the basis for a simple
      and reliable assay for measuring JNK activity in cells stimulated with Wnt
      proteins and growth factors.

PMID- 19099256
TI  - ROCK enzymatic assay.
AB  - We describe the protocols for measuring Rho-associated coiled-coil-containing
      kinase (ROCK) activity in vitro. A His-tagged, constitutively active form of the
      protein (lacking C-terminal inhibitory domains) is expressed in baculovirus. The
      protein is purified by a combination of metal affinity, ion exchange, and size
      exclusion chromatography. Enzymatic activity is measured spectrophotometrically
      in a coupled assay format wherein a molecule of NADH is oxidized to NAD+ each
      time a phosphate is transferred by ROCK.

PMID- 19099257
TI  - Detection of planar polarity proteins in mammalian cochlea.
AB  - The "core genes" were identified as a group of genes believed to function as a
      conserved signaling cassette for the specification of planar polarity in
      Drosophila Melanogaster, and includes frizzled (fz), van gogh (vang) or
      strabismus (stbm), prickle (Pk), dishevelled (dsh), flamingo (fmi), and diego.
      The mutation of each of these genes not only causes the disruption of planar
      polarity within the wing or the eye of the animal, but also affects the
      localization of all the other protein members of the core group. These properties
      emphasize the importance of the interrelations between the proteins of this
      group. All of these core genes have homologs in vertebrates. Studies in Danio
      Rerio (zebrafish) and Xenopus laevis (frog) have uncovered other roles for some
      of these molecules in gastrulation and neurulation, during which the shape of a
      given tissue will undergo major transformation through cell movements. A
      disruption in these processes can lead to severe neural tube defects in diverse
      organisms, including humans. In fact, a large body of evidence suggests that
      planar polarity proteins are not involved in one specific cascade but in many
      different ones and many different mechanisms such as, but not limited to, hair or
      cilia orientation, asymmetric division, cellular movements, or neuronal
      migration. In mice cochleae, mutations in planar polarity genes lead to defects
      in the orientation of the stereociliary bundles at the apex of each hair cell.
      This phenotype established the cochlea as one of the clearest examples of planar
      polarity in mammals. Although significant progress has been made toward
      understanding the molecular basis required for the development of planar polarity
      in invertebrates, similar advances in vertebrates are more recent and rely mainly
      on the identification of a group of mammalian mutants that affect hair cell
      stereociliary bundle orientation. These include mutation of vangl2, scrb1,
      celsr1, PTK-7, dvl1-2, and more recently fz3 and fz6. In this chapter, we
      describe how to use the mammalian cochlea, which represents one of the best
      systems to study planar polarity in mammals, to identify planar polarity mutants,
      study protein distribution, do in vitro analysis, and perform Western blots to
      analyze putative planar polarity proteins.

PMID- 19099258
TI  - Proteomic analyses of protein complexes in the Wnt pathway.
AB  - Multiple screens performed in Drosophila, Caenorhabditis elegans, Xenopus, and
      zebrafish have identified dozens of proteins participating in Wnt signal
      transduction. Epistasis experiments, enhancer and suppressor screens, and protein
      protein interaction techniques have also been efficient at finding new pathway
      members, connecting proteins together, and establishing the architectural
      framework of how the Wnt signaling pathway functions. In the last few years,
      spectacular technological breakthroughs in the field of mass spectrometry have
      allowed the study of proteins and peptides with unprecedented sensitivity and
      accuracy. Recently, we have developed methods to study the Wnt pathway using mass
      spectrometry by studying the composition of protein complexes isolated from
      mammalian cells. In addition to identifying novel proteins acting in this
      pathway, this approach is providing information about the supramolecular
      organization of the protein complexes in the pathway and how the individual
      proteins are activated and regulated. This chapter details the experimental
      procedure that we developed to study mammalian protein complexes using a gel-free
      mass spectrometry approach.

PMID- 19099259
TI  - In situ hybridization to evaluate the expression of Wnt and frizzled genes in
      mammalian tissues.
AB  - In situ hybridization can be utilized to specifically define the expression of
      genes and to determine their localization in complex mammalian tissues. The
      expression of specific members of the Wnt ligand and frizzled receptor families
      of molecules can be defined using an antisense RNA probe that will specifically
      hybridize with messenger RNA (mRNA) in the tissue to form a double-stranded
      product. The double-stranded product can then be detected microscopically by
      identifying digoxigenin groups that are attached to the probe during its
      synthesis. Probe sequence selection is critical to ensure specificity among
      different Wnt or frizzled family members. Controls are needed at every step in
      the technique to confirm appropriate quality of the tissue sections, quality of
      the prepared probe, and specificity of the hybridization reactions. If performed
      properly, in situ hybridization can be utilized to define gene expression and
      specific localization of RNA in human and other mammalian tissues, and can be
      utilized in previously fixed and paraffin-embedded tissue samples.

PMID- 19099260
TI  - Assaying Wnt5A-mediated invasion in melanoma cells.
AB  - Wnt5A has been implicated in melanoma metastasis, and the progression of other
      cancers including pancreatic, gastric, prostate, and lung cancers. Assays to test
      motility and invasion include both in vivo assays and in vitro assays. The in
      vivo assays include the use of tail vein or footpad injections of metastatic
      cells, and are often laborious and expensive. In vitro invasion assays provide
      quick readouts that can help to establish conditions that either activate or
      inhibit melanoma cell motility, and to assess whether the conditions in question
      are worth translating into an in vivo model. Here we describe two standard
      methods for assaying motility and invasion in vitro including wound healing
      assays and Matrigel invasion assays (Boyden chamber assays). In addition, we and
      several other laboratories have previously shown that melanoma cells require
      matrix metalloproteinase (MMP)-2 for their invasion, and have recently shown that
      Wnt5A treatment can increase the levels of this enzyme in melanoma cells, as
      demonstrated by gelatin zymography. The use of these techniques can help to
      assess the migratory capacity of melanoma cells in response to Wnt treatment.

PMID- 19099261
TI  - Coculture methodologies for the study of Wnt signals.
AB  - In vivo, responses to extracellular Wnt ligands are context dependent; the
      temporal characteristics and intensity of the signal are critical in determining
      the target cell response. In general, Wnt ligand-induced differentiation in
      mammalian cells requires several days of exposure. In order to better
      characterize Wnt-induced signaling in vitro, side-by-side and partitioned
      cocultures can be utilized. These methodologies closely mimic how Wnt signals are
      transmitted in the tumor microenvironment.

PMID- 19099262
TI  - Analysis of Wnt/FZD-mediated signalling in a cell line model of colorectal cancer
      morphogenesis.
AB  - Cells in tissues do not exist as isolated entities but are part of the three
      dimensional tissue architecture. Consequently, some aspects of cell behaviour
      cannot be mimicked by simple in vitro monolayer culture systems. Moreover, cell
      shape and behaviour is not rigid but is dynamic and can be regulated by intrinsic
      and extrinsic factors. For example, tumour cells in epithelium-derived cancer
      such as colorectal cancer often retain significant features of the colonic
      mucosa. However, as the tumour progresses, the morphology of the tumour cells
      often undergoes a transition from an epithelial morphology to a mesenchymal
      morphology. This transition is important as it signifies a change in the tumour
      phenotype to a more aggressive, invasive, and eventually metastatic phenotype. In
      vitro models that allow the study of this transition are needed. One such model
      is the LIM1863 colon carcinoma cells that normally grow as organoids but can be
      adapted to efficiently undergo an epithelial to mesenchymal transition that can
      be reversed. This system has allowed the study of the genes such as Frizzled 7
      that are involved in this dynamic and reversible epithelial to mesenchymal
      transition.

PMID- 19099263
TI  - Analysing tissue and gene function in intestinal organ culture.
AB  - The study of growth, differentiation, and migration of different cell types
      within the developing intestine has been enhanced by the development of methods
      to grow intestinal tissue in organ culture. Here, we describe the innovative
      method of catenary culture where the tubular architecture of the intestine is
      maintained and normal cell differentiation occurs. Rapid analysis of gene
      function can be achieved using low voltage, square wave electroporation to
      introduce expression constructs into the epithelial cell layer of cultured
      explants. This whole-organ culture system allows cells, signalling pathways, and
      gene function to be analysed in intact explants of embryonic gut that are
      accessible for experimental manipulation and live cell imaging.

PMID- 19099264
TI  - Genetics of Wnt signaling during early mammalian development.
AB  - Proper cell-cell communication is necessary to orchestrate the cell fate
      determination, proliferation, movement, and differentiation that occurs during
      the development of a complex, multicellular organism. Members of the Wnt family
      of secreted signaling molecules regulate these processes in virtually every
      embryonic tissue and during the homeostatic maintenance of adult tissues.
      Mammalian genetic studies have been particularly useful in illustrating the
      specific roles that Wnt signaling pathways play in embryonic development, and in
      the etiology of diseases such as cancer. This chapter will largely focus on the
      functional roles that Wnts, signaling through the Wnt/-catenin pathway, play
      during early mammalian development.

PMID- 19099265
TI  - Tissue-specific transgenic, conditional knockout and knock-in mice of genes in
      the canonical Wnt signaling pathway.
AB  - The Wnt signaling pathway plays key roles in the development and homeostasis of a
      number of organs such as the brain, lung, liver, heart, gastrointestinal tract,
      mammary gland, skin, and bone, as well as of the immune system. Studies on
      conventional knockout mice of the genes in the Wnt signaling pathway have
      revealed its essential roles in these tissues; however, most of these knockout
      mice die during embryogenesis or soon after birth. Through more advanced
      techniques such as Cre/loxP and tetracycline-inducible systems, a gene of
      interest can be expressed or inactivated in a tissue-specific and time-controlled
      manner. Here we review recent papers on the tissue-specific transgenic,
      conditional knockout and knock-in mice of the genes in the Wnt signaling pathway
      In addition to such engineered mice, we also list reporter mice that have been
      generated to determine the activity of the canonical Wnt signaling pathway in
      mouse tissues.

PMID- 19099266
TI  - [Design and evaluation of the University of Munich courses on research trials].
AB  - INTRODUCTION: The growing importance of clinical research in Germany requires
      physicians who are adequately trained to conduct clinical trials. In November
      2007, the Coordination Centre for Surgical Studies at the University of Munich
      organised its third course for clinical investigators. The course was evaluated
      by the participants. PARTICIPANTS AND PROGRAMME: Participants included 1st-year
      residents as well as specialists mostly from surgical departments; many already
      possessed significant experience with clinical trials. In our course, special
      emphasis was put on the practical aspects of conducting clinical trials.
      EVALUATION: On a scale from 1 to 6 (in German grading, 1 is the best score),
      participants rated content at 1.5, understanding at 1.6, and learning effect at
      1.8. Careful preparation and a clearly structured curriculum resulted in
      significantly better evaluation of this course than of preceding courses (content
      P=0.015, understanding P=0.007, learning effect P=0.018). DISCUSSION: To realise
      projects of translational investigation and to participate in interdisciplinary
      clinical trials, surgeons in academic centres should obtain basic knowledge on
      clinical and pharmaceutical trials. Participants' statements on their own
      experience as clinical investigators underline the need for adequate training in
      this field. This course conveys essential knowledge of good medical practice and
      critical review of medical literature. We view this knowledge as a basic skill
      for modern medical practice and have therefore integrated the course into basic
      surgical training at our department. CONCLUSION: The concept of training for
      clinical investigation conducted at a surgical department is well established,
      and the participants' positive feedback motivates us to continue organising such
      courses.

PMID- 19099267
TI  - [Minimally invasive resection of neuroendocrine pancreatic tumors].
AB  - Pancreatic endocrine tumors (PET) are a heterogeneous group of lesions with an
      annual incidence of 0.1 to 0.4 per 100,000. They account for 2-4% of pancreatic
      neoplasms. Due to their mostly small size, some are suited to a laparoscopic
      approach. Preoperative localization, intraoperative laparoscopic ultrasonography,
      and considerable experience in pancreatic endocrine surgery and sophisticated
      laparoscopic techniques are essential for successful laparoscopic treatment of
      these tumors. If definite or highly suspicious signs of malignancy occur, a
      conventional open approach should be preferred. Insulinomas and small
      nonfunctioning PET in the pancreatic body or tail or near the surface of the
      pancreatic head and not in contact with the portal vein or the main pancreatic
      duct are suited to a laparoscopic approach. Patients with MEN1 who have
      insulinomas or small nonfunctioning PET may also benefit from a laparoscopic
      spleen-preserving distal pancreatic resection. Neither sporadic and MEN1
      associated gastrinomas nor the very rare glucagonomas and vasoactive intestinal
      peptide-producing tumors (vipomas), which are often large and malignant, should
      also be tackled laparoscopically.

PMID- 19099268
TI  - [New contact allergens for patch testing. A phase-out-model?].
AB  - To insure the quality in diagnosis of allergic contact dermatitis, patch test
      series need to be continuously actualized. This work is done by the German
      Contact Dermatitis Research Group. The regulations for epidemiologic studies in
      patch testing have been sharpened by the recent revision of the German Drug
      Registration and Administration Act which defines patch test allergens to be
      equivalent to medications. As a result of this, the transfer of scientific data
      on new contact sensitizers into practice and their registration as medicines for
      use in patch testing are blocked. Examples for potentially relevant new
      sensitizers, which should be made available for routine patch testing and
      strategies to handle the requirements of the Drug Registration and Administration
      Act are discussed. In addition, the consequences of the present regulation of
      payment for patch testing by the German Uniform Value Scale are presented. The
      disconnection of the total fee for the diagnosis of allergic contact dermatitis
      from the number of patch tests leads to a reduced depth of diagnostic approach.
      In future, this may become a serious threat for the quality of patch testing in
      dermatology.

PMID- 19099270
TI  - [Sensitisation to p-Phenylenediamine. Effects of metabolism and individual
      susceptibility].
AB  - Due to its constant exposure to small molecular weight compounds, the skin is a
      major target for allergic reactions. Para-phenylenediamine (PPD) is a common and
      strong contact allergen. Recent studies have revealed new aspects of steps
      involved in sensitization and allergic contact dermatitis to PPD, giving insight
      into the cutaneous metabolism of small molecular compounds and its effect on
      activation and deactivation of immunogenic substances. Molecular epidemiological
      studies have suggested that polymorphisms in genes encoding cytokines (e.g. TNF
      alpha) or metabolizing enzymes (e.g. N-acetyltransferase) may have influence on
      these mechanisms and the individual susceptibility for sensitization.

PMID- 19099269
TI  - [Facial allergic contact dermatitis. Data from the IVDK and review of
      literature].
AB  - The face is exposed to many foreign substances and may thus be a site of allergic
      contact dermatitis. Our aim is to elucidate the spectrum of factors associated
      with facial dermatitis by analyzing data of patients patch tested in the
      Information Network of Departments of Dermatology (IVDK) between 1995 and 2007.
      In 18,572 patients the main anatomical site of dermatitis was the face. Among
      these, the proportion of females and of patients with past or present atopic
      eczema was increased, while probable occupational causation was less common than
      in the overall group. Cosmetic allergens, as well as nickel, were significantly
      more common in women than men, including fragrance mix (10.8% vs. 8.3%), p
      phenylenediamine (4.0% vs. 2.8%), lanolin alcohols (3.0% vs. 2.2%), Lyral(TM)
      (3.1% vs. 2.0%) and bufexamac (1.8% vs. 1.1%). In comparison, only epoxy resin
      contact allergy was diagnosed significantly more often in men than women: In
      patients with airborne contact dermatitis, over-represented allergens included
      sesquiterpene lactone mix, compositae mix, epoxy resin, (chloro-)
      methylisothiazolinone and oil of turpentine. In the clinical approach to patients
      with facial dermatitis, occupational airborne causation should be considered in
      addition to non-occupational (e.g., cosmetic) allergen exposure.

PMID- 19099271
TI  - [Immunology of allergic contact dermatitis].
AB  - Eczema is one of the most common skin diseases in dermatological practice. The
      broad medical definition of eczema includes any acute but non-infectious
      inflammatory reaction of the skin. The relative homogeneity of both the clinical
      and histological manifestations of eczema is in stark contrast to the profound
      pathogenetic differences of its various forms. The group of contact dermatitis
      can be divided into two main categories: irritant and allergic. Irritant contact
      dermatitis is due to a principally non- immunological inflammatory reaction of
      the skin to various physical or chemical irritants. In sharp contrast, allergic
      contact dermatitis is an antigen-specific cellular immune response of the skin,
      which in general requires prior antigen-recognition and priming of immune cells.
      A comprehensive understanding of the complex interactions between immune cells,
      inflammatory mediators and adhesion molecules in the underlying pathogenesis of
      allergic contact dermatitis is key for a better functional understanding and the
      development of new therapeutic strategies.

PMID- 19099272
TI  - [Expiratory vocal cord dysfunction? Case report and review of the literature].
AB  - Wood and Milgrom defined vocal cord dysfunction (VCD) as paradoxical adduction of
      the vocal folds during inspiration or during inspiration and expiration. We
      describe the case of a patient with attacks of dyspnea with an isolated
      expiratory paradoxical adduction of the vocal folds. A review of the literature
      reveals many factors associated with VCD. Because of the similar risk factors and
      order of events concerning VCD, we believe that even expiratory laryngeal
      dysfunctions could be denoted as subtypes of VCD.

PMID- 19099273
TI  - [Polymyalgia rheumatica].
AB  - Polymyalgia rheumatica (PMR) is a common chronic inflammatory rheumatic disease
      with unknown aetiology, affecting predominately people of middle age and older.
      Besides clinical symptoms and diagnostics, imaging techniques including
      sonography and magnetic resonance imaging may provide evidence of typical
      inflammatory lesions with bilateral bursitis subdeltoidea or subacromialis,
      tenosynovitis of the biceps tendon sheath and/or synovitis of the shoulder joints
      and thus may support the diagnosis of this disease in difficult cases.
      Corticosteroids are the cornerstone of treatment of PMR, but adverse events
      because of chronic corticosteroid use are observed in more than 50% of treated
      patients. Whether immunosuppressants, such as methotrexate and tumour necrosis
      factor-alpha inhibitors are effective in the therapy of PMR has still not yet
      been clarified.

PMID- 19099274
TI  - [64-year old patient with tachycardia and signs of heart failure].
AB  - We report on a 64-year old patient with known Morbus Osler and high cardiac
      output failure due to distinct arterio-venous malformations of the liver. Since
      the patient suffered from severe right heart insufficiency despite optimized
      medical therapy, we decided to conduct an interventional occlusion of the hepatic
      shunts in three single sessions. The transient elevation of transaminases was
      reversible. After interventional therapy cardiac output decreased from 20 l/min
      to 15 l/min (25%) leading to a reduction of diuretic dosage and a sustained
      stabilization of the clinical condition.

PMID- 19099275
TI  - [Adverse drug reactions and the skin--from trivial to fire signal].
AB  - Adverse drug reactions are a common medical problem. Especially hypersensitivity
      reactions are mostly impressive and unsettling due to their nature of being not
      dose-dependent and non-predictable. Clinical manifestations of the skin comprise
      manifold appearances from mild macular exanthems to bullous eruptions, and
      urticaria, angioedema to anaphylaxis. Systemic hypersensitivity reactions can
      affect nearly all internal organs and cells. Characteristic clinical danger signs
      for severe allergic drug reactions, for immediate type as well as for delayed
      type manifestations, help to recognise the incipient allergic drug reaction, to
      stop the further administration of the potential elicitor/allergen and to start
      therapeutic actions. It is essential for the success of a further allergologic
      work-up of such reactions to describe and document accurately the morphologic
      characteristics of the skin and other organ manifestations and the exact time
      course of medication intake and development of the clinical adverse reaction.
      This facilitates the choice of adequate diagnostic measures and the
      interpretation of the respective results.

PMID- 19099276
TI  - [Mucocutaneous infections in immunosuppression].
AB  - The skin has several physical, chemical and immunological properties which help
      to protect the internal organs. In addition, there is a physiological
      colonisation of commensal microbes which help to suppress the expansion of
      pathogenic germs on the skin. Genetic or acquired immunodeficiency will have an
      impact to these factors. Drug induced immunodeficiency is common in organ
      transplanted patients with the aim to prevent organ rejection. HIV infection most
      commonly leads without therapy to marked immune suppression. Such patients with
      prolonged immunodeficiency often develop atypical manifestation of mucocutaneous
      infections. Therefore such patients should be biopsied liberally and besides the
      conventional histology a part of the biopsied tissue should be used for
      microbiological cultures. In addition to acute infections of the skin, long-term
      effects of oncogenic viruses have to be taken in account which can lead to
      epithelial cancers (HPV), Kaposi sarcomas (HHV8) and lymphomas (EBV). There are
      mucocutaneous markers for immunosuppression such as oral hairy leukoplakia, which
      are commonly seen in AIDS patients but may also be observed in otherwise
      chronically immune suppressed patients. This work gives an overview to the
      pathophysiology of skin protection and describes typical mucocutaneous infections
      in immune suppressed patients.

PMID- 19099277
TI  - [Pheochromocytoma - still a challenge].
AB  - Pheochromocytomas are rare, mostly benign catecholamine-producing tumors arising
      from the chromaffin cells of the adrenal medulla or in the paraganglia. Clinical
      presentation is highly variable but typically with hypertension, severe
      headaches, palpitations and sweating. Biochemical testing by 24 h urinary
      fractioned metanephrines or catecholamines and plasma free metanephrines as the
      most sensitive screening approach, confirms the catecholamine excess. Computed
      tomography scan and magnetic resonance imaging of the adrenal glands and abdomen
      as well as functional imaging with (123)Iod-MIBG scintigraphy and (18)F-dopa
      positron emission tomography are used for tumor localization. Because
      approximately a quarter of tumors develop secondary to germ-line mutations,
      screening for genetic alterations is important. The therapy of choice is the
      endoscopic adrenal sparing surgery following preoperative alpha-blockade. Regular
      follow-up remains essential due to possible recurrence and malignancy.

PMID- 19099278
TI  - [Conn's syndrome].
AB  - The primary hyperaldosteronism (PHA) is the most prevalent form (8-10%) of
      secondary causes of hypertension among hypertensive subjects. This will result in
      2 to 2.5 million people suffering from PHA in Germany. Screening for PHA should
      be performed by measuring the aldosterone-renin ratio in the morning. The current
      antihypertensive medication should be taken into account. A suspicious ratio must
      lead to a confirmatory test to validate the diagnosis of PHA. For further PHA
      subtype investigation adrenal imaging is performed using CT or MRI. Adrenal
      venous sampling is often required to definitively confirm uni- or bilateral
      aldosterone hypersecretion. The aldosterone-producing adenoma (Conn's syndrome)
      is primarily cured by endoscopical unilateral adrenalectomy. Bilateral
      hyperplasia, which is found in two-thirds of primary hyperaldosteronism, is
      treated primarily by a mineralocorticoid receptor antagonist (12.5-100 mg/day
      spironolactone). The start of medication should be closely monitored by serum
      electrolyte and creatinine controls.

PMID- 19099279
TI  - A novel peptide motif binding to and blocking the intracellular activity of the
      human papillomavirus E6 oncoprotein.
AB  - Specific types of human papillomaviruses (HPVs) cause cervical cancer. The viral
      E6 oncogene is a critical factor for maintaining the malignant phenotype of HPV
      positive tumour cells. By yeast two-hybrid screening of a randomised peptide
      expression library, we isolated linear short peptides, which specifically bind to
      the HPV16 E6 oncoprotein. Sequence alignments and mutational analyses of the
      peptides identified a hitherto undiscovered E6-binding motif. Intracellular
      expression of a peptide containing the novel E6-binding motif resulted in
      inhibition of colony formation capacity, specifically of HPV16-positive cancer
      cells. A solubility-optimised variant of the peptide was created, which binds to
      HPV16 E6 with high affinity. Its intracellular expression efficiently induced
      apoptosis in HPV16-positive cancer cells. This was linked to restoration of
      intracellular p53 activities. Thus, this newly identified E6-binding motif could
      form a novel basis for the development of rational strategies for the treatment
      of HPV16-positive preneoplastic and neoplastic lesions.

PMID- 19099280
TI  - [Operative treatment of traumatic fractures of the thoracic and lumbar spinal
      column. Part I: epidemiology].
AB  - The Spine Study Group (AG WS) of the German Trauma Association (DGU) has now been
      in existence for more than a decade. Its main objective is the evaluation and
      optimization of the operative treatment for traumatic spinal injuries. The
      authors present the results of the second prospective internet-based multicenter
      study (MCS II) of the AG WS in three consecutive parts: epidemiology, surgical
      treatment and radiologic findings and follow-up results. The aim of the study was
      to update and review the state-of-the art for treatment of spinal fractures for
      thoracic and lumbar spine (T1-L5) injuries in German-speaking countries: which
      lesions will be treated with which procedure and what differences can be found in
      the course of treatment and the clinical and radiological outcome? This present
      first part of the study outlines the new study design and concept of an internet
      based data collection system. The epidemiologic findings and characteristics of
      the three major treatment subgroups of the study collective will be presented:
      operative treatment (OP), non-operative treatment (KONS), and patients receiving
      a kyphoplasty and/or vertebroplasty without additional instrumentation (PLASTIE).
      A total of 865 patients (OP n=733, KONS n=52, PLASTIE n=69, other n=7) from 8
      German and Austrian trauma centers were included. The main causes of accidents in
      the OP subgroup were motor vehicle accidents 27.1% and trivial falls 15.8% (KONS
      55.8%, PLASTIE 66.7%). The Magerl/AO classification scheme was used and 548
      (63.3%) compression fractures (type A), 181 (20.9%) distraction injuries (type
      B), and 136 (15.7%) rotational injuries (type C) were diagnosed. Of the fractures
      68.8% were located at the thoracolumbar junction (T11-L2). Type B and type C
      injuries carried a higher risk for concomitant injuries, neurological deficits
      and additional vertebral fractures. The average initial VAS spine score,
      representing the status before the trauma, varied between treatment subgroups (OP
      80, KONS 75, PLASTIE 72) and declined with increasing patient age (p<0.01).

PMID- 19099281
TI  - [Validation of the prehospital mSTaRT triage algorithm. A pilot study for the
      development of a multicenter evaluation].
AB  - INTRODUCTION: Successful management of a mass casualty incident requires
      integrated operating procedures. A common division of victims into descriptive
      needs-based groups and the corresponding decision processes is the key to
      ensuring a successful operational response. The mSTaRT ("modified simple triage
      and rapid treatment") algorithm should enable emergency medical technicians to
      conduct triage, perform appropriate medical interventions, and coordinate
      transportation to adequate care facilities. The aim of this study was to design a
      concept to validate the mSTaRT algorithm. METHODS: Standardized evaluation sheets
      were distributed to emergency medical services (EMS) staff to prospectively
      classify trauma patients according to the mSTaRT algorithm: red (immediate:
      critically injured patients who can be helped by immediate transport), yellow
      (urgent: severely injured patients whose transport can be delayed), or green
      (delayed: patients with minor injuries who need help less urgently). The patients
      were then reevaluated in the emergency department, and the results were compared.
      The main points of the comparison were consistency of triage category and rates
      of overtriage and undertriage. RESULTS: The study included 151 trauma patients.
      Of these, 62.3% were triaged correctly, 10.6% were overtriaged (2.6% critical
      overtriage), and 27.1% were undertriaged (4.0% critical undertriage). In the
      critically injured (immediate) category, the positive likelihood ratio (LR+) was
      17.3 (95% CI 3.8-795), and the negative likelihood ratio (LR-) was 0.51 (95% CI
      0.22-0.83). The probability of identifying a critically injured (immediate)
      patient was 17.3 times higher than the probability of identifying a severely
      (urgent) or minor (delayed) injured patient as immediate. Therefore, the rate of
      overtriage was very low. But every second patient who should have been classified
      as immediate was undertriaged by the EMS personnel. This undertriage was due to
      patients' suffering from head trauma, a well-known problem in the clinical
      context but a new problem in the triage context. CONCLUSION: The results of our
      pilot study show that by using mSTaRT, patients designated as yellow (urgent) and
      green (delayed) will be accurately distinguished from red (immediate) patients;
      therefore, only a small number of patients will be overtriaged as red. However,
      some patients with severe head injury may not be initially assigned to the red
      category as required, resulting in undertriage. Consequently, modification of the
      mSTaRT procedures should be considered. A further identifier in the algorithm or
      checkpoint in the process should act as a safety net for catching severe head
      injury. A larger data set is required to further validate the mSTaRT algorithm.
      This will be acquired by means of a multicenter study.

PMID- 19099282
TI  - [Ten years' experience at a major stroke center].
AB  - BACKGROUND: About 1,300 stroke patients from a primarily rural area are treated
      each year at the Department of Neurology of the University Hospital of
      Heidelberg, Germany. Demographic and treatment data of all stroke patients there
      were prospectively collected. In a retrospective study we report on the changes
      in this patient population from 1996 to 2006, with special consideration of those
      suitable for intravenous thrombolysis. METHODS: For all stroke patients the basic
      data were collected--age, sex, type of stroke (transient ischemic attack, stroke,
      or intracerebral hemorrhage), NIH Stroke Scale, duration between symptom onset
      and hospital arrival, delay between arrival and first doctor's contact, patient's
      further whereabouts, and for patients treated by iv thrombolysis, start of
      treatment and dosage. RESULTS: There were no changes in the total number of
      stroke patients and median stroke severity, according to the NIH Stroke Scale,
      from 1996 to 2006. The proportion of stroke patients admitted within the first 3
      h after symptom onset increased from 12.1% (1996) to 21.9% (2006). Thus we
      managed to treat 10.1% of all our ischemic stroke patients with iv thrombolysis,
      which means 39% of those patients with cerebral infarction arriving within 3 h.
      DISCUSSION: During the study period there were no significant changes in the
      patients' sociodemographic data. By consistent reduction of prehospital delay,
      the number of stroke patients that could be treated acutely by intravenous
      thrombolysis was increased.

PMID- 19099283
TI  - [The significance of lymphadenectomy in the management of penile cancer].
AB  - Inguinal lymphadenectomy is performed according to the clinical features as well
      as the risk factors of the primary tumor. In cases involving more than two
      positive lymph nodes or extranodal growth as well as positive imaging, pelvic
      lymphadenectomy is indicated. Large or fixed inguinal nodes as well as iliac
      lymph nodes seen on computed tomography scanning are a good indication for
      neoadjuvant rather than adjuvant chemotherapy.

PMID- 19099284
TI  - Comparative genetic linkage map of Solanum sect. Juglandifolia: evidence of
      chromosomal rearrangements and overall synteny with the tomatoes and related
      nightshades.
AB  - The two nightshades Solanum ochranthum and S. juglandifolium show genetic and
      morphological similarities to the tomatoes (Solanum sect. Lycopersicon), but are
      isolated from them by strong reproductive barriers. Their genetic relationships
      to tomato and other Solanum species were investigated using comparative genetic
      linkage maps obtained from an interspecific F(2) S. ochranthum x S.
      juglandifolium population. Sixty-six plants were screened using a total of 132
      markers--CAPs, RFLPs and SSRs--previously mapped in tomato. Twelve linkage groups
      were identified, generally corresponding to the expected (syntenic) tomato
      chromosomes, with two exceptions. Chromosome 1 was composed of two linkage groups
      and chromosomes 8 and 12 were connected in one large linkage group, indicating a
      likely reciprocal translocation differentiating the two parental genomes. The
      total map length comprised 790 cM, representing a 42% reduction in recombination
      rate relative to the tomato reference map. Transmission ratio distortion affected
      one-third of the genome, with 13 putative TRD loci identified on 9 out of 12
      chromosomes. Most regions were collinear with the tomato reference maps,
      including the long arm of chromosome 10, which is inverted relative to two other
      tomato-like nightshades, S. lycopersicoides and S. sitiens. The results support
      the status of S. ochranthum and S. juglandifolium as the nearest outgroup to the
      tomatoes and imply they are more closely related to cultivated tomato than
      predicted from crossing relationships, thus encouraging further attempts at
      hybridization and introgression between them.

PMID- 19099285
TI  - Genetic analysis of nuclear-cytoplasmic incompatibility in pea associated with
      cytoplasm of an accession of wild subspecies Pisum sativum subsp. elatius (Bieb.)
      Schmahl.
AB  - The genetic basis of nuclear-cytoplasmic incompatibility was examined using the
      wild pea (Pisum sativum subsp. elatius) accession VIR320. When this accession is
      used as the female parent in crosses with domesticated peas (Pisum sativum subsp.
      sativum) the F(1) is highly sterile and displays chlorophyll deficiency,
      chlorophyll variegation, reduction of leaflets and stipulae while the reciprocal
      cross produces hybrids that appear normal. A mapping recombinant inbred line
      (RIL) population was established based on a cross in a compatible direction of a
      tester line WL1238 with VIR320. The ability to cause nuclear-cytoplasmic conflict
      was analysed by crossing individual RIL plants as pollen parents with VIR320 as
      donor of cytoplasm and scoring each F(1) for major signs of the conflict. It is
      concluded that two unlinked nuclear genes are involved in the genetic control of
      the observed incompatibility. One of the genes, denoted as Scs1, is closely
      linked to the PhlC gene on linkage group III and the other, denoted as Scs2, is
      closely linked to the gp gene on linkage group V. Alleles of both genes in WL1238
      are dominant and appear to be lethal in the homozygous condition in the VIR320
      cytoplasm background.

PMID- 19099286
TI  - [Arthroscopic ventral shoulder stabilization].
AB  - Traumatic antero-inferior dislocation of the shoulder is a common injury among
      the young athletic population. The incidence of reluxation after conservative
      treatment in young patients is up to 80%. Arthroscopic antero-inferior shoulder
      stabilization has become the gold standard in recent years due to technical and
      material improvement. The recurrence rate after arthroscopic and open surgery is
      similar (approximately 6.5%), but morbidity after arthroscopic surgery is less.
      The authors of this paper advise the use of suture anchors for refixation of the
      capsulolabral complex. An antero-inferior approach is used for ideal positioning
      of the anchors on the glenoid rim and lesions of the superior biceps tendon or
      other co-morbidities can be addressed at the same time. In conclusion
      arthroscopic shoulder stabilization is an appropriate treatment for antero
      inferior shoulder dislocation.

PMID- 19099287
TI  - Non-occlusive colonic ischemia induced by verapamil ER overdose.

PMID- 19099288
TI  - Influence of surgical treatment timing on mortality from necrotizing soft tissue
      infections requiring intensive care management.
AB  - PURPOSE: Surgical treatment is crucial in the management of necrotizing soft
      tissue infections (NSTIs). The aim of this study was to determine the influence
      of surgical procedure timing on hospital mortality in severe NSTI. METHODS: A
      retrospective study including 106 patients was conducted in a medical intensive
      care unit equipped with a hyperbaric chamber. Data regarding pre-existing
      conditions, intensive care and surgical management were included in a logistic
      regression model to determine independent factors associated with hospital
      mortality. RESULTS: Overall hospital mortality was 40.6%. In multivariate
      analysis, underlying cardiovascular disease, SAPS II, abdominoperineal compared
      to limb localization, time from the first signs to diagnosis <72 h, and time from
      diagnosis to surgical treatment >14 h in patients with septic shock were
      independently associated with hospital mortality. CONCLUSION: In patients with
      NSTI and septic shock, hospital mortality is influenced by the timing of surgical
      treatment.

PMID- 19099289
TI  - Intraoperative evaluation of total knee replacement: kinematic assessment with a
      navigation system.
AB  - Interest in the kinematics of reconstructed knees has increased since it was
      shown that the alteration of knee motion could lead to abnormal wear and damage
      to soft tissues. We performed intraoperative kinematic measurements using a
      navigation system to study knee kinematics before and after posterior
      substituting rotating platform total knee arthroplasty (TKA). We verified
      intraoperatively (1) if varus/valgus (VV) laxity and anterior/posterior (AP)
      laxity were restored after TKA; (2) if TKA induced abnormal femoral rollback; and
      (3) how tibial axial rotation was influenced by TKA throughout the range of
      flexion. We found that TKA improved alignment in preoperative osteoarthritic
      varus knees which became neutral after surgery and maintained a neutral alignment
      in neutral knees. The VV stability at 0 degrees was restored while AP laxity at
      90 degrees significantly increased after TKA. Following TKA, the femur had an
      abnormal anterior translation up to 60 degrees of flexion, followed by a small
      rollback of 12 +/- 5 mm. TKA influenced the tibia rotation pattern during
      flexion, but not the total amount of internal/external rotation throughout whole
      range of flexion, which was preserved after TKA (6 degrees +/- 5 degrees ). This
      study showed that the protocol proposed might be useful to adjust knee stability
      at time zero and that knee kinematic outcome during total knee replacement can be
      monitored by a navigation system.

PMID- 19099290
TI  - A comparison of modified Larson and 'anatomic' posterolateral corner
      reconstructions in knees with combined PCL and posterolateral corner deficiency.
AB  - Different methods to reconstruct damaged posterolateral structures are available,
      but there has been little work studying their relative performance in combined
      PCL plus posterolateral corner (PLC) deficiency. We hypothesized that an
      'anatomic' reconstruction with three graft bundles crossing the joint line would
      restore knee laxity closer to normal than a modified two-bundle Larson
      reconstruction. In a controlled laboratory study, the kinematics of cadaveric
      knees were measured electromagnetically with posterior drawer, external rotation,
      or varus rotation loads applied, with the knee at sequential stages: intact, PCL
      deficient; PCL plus PLC-deficient; modified Larson reconstruction; anatomic PLC
      reconstruction. The graft bundles were tensioned sequentially to restore specific
      degrees of freedom to intact values of laxity at specific angles of knee flexion.
      A significant difference was not found between the two reconstructions. Both
      reconstructions restored external rotation and varus laxity to normal. Both
      restored posterior drawer to that caused by isolated PCL deficiency, but did not
      restore posterior laxity to normal. It was concluded that, with appropriate graft
      tensioning, both PLC reconstructions could restore both external rotation and
      varus laxity to normal, but not posterior drawer. The three-stranded anatomical
      reconstruction did not perform better than the modified two-strand Larson
      technique. Both of these isolated PLC reconstructions in knees with combined PCL
      plus PLC deficiency restored the knees to the laxity condition of an isolated PCL
      deficiency, they could not reduce posterior drawer to normal.

PMID- 19099291
TI  - An unusual periarticular fracture following ipsilateral anterior cruciate
      ligament reconstruction.
AB  - We report an unusual pattern of a peri and intra-articular knee fracture
      following ACL reconstruction. The pattern of injury was opposite to the graft
      tunnels which contradicts the well established iatrogenic stress riser theory
      which has been extensively described in the literature. The fractures were
      reduced anatomically by open means, the graft was found intact and preserved and
      the fractures were fixed internally protecting the graft and the tunnels. The
      patient made an uneventful recovery and the post operative MRI scan 12 months
      later demonstrated bone healing and an intact ACL. When the ACL graft is found
      intact in this type of injury, the fracture should be fixed around it taking care
      not to jeopardize its integrity or the tunnels.

PMID- 19099292
TI  - Does the dosage matter in sclerosing polidocanol injections in Achilles
      tendinopathy?

PMID- 19099293
TI  - Is previous knee arthroscopy related to worse results in primary total knee
      arthroplasty?
AB  - According to literature, knee arthroscopy is a minimal invasive surgery performed
      for minor surgical trauma, reduced morbidity and shortens the hospitalization
      period. Therefore, this type of surgery before total knee arthroplasty (TKA)
      could be considered a minor procedure with minimum postoperative complication. A
      retrospective and cohort series of 1,474 primary TKA was performed with re
      assessment after a minimum follow-up period of 2 years: 1,119 primary TKA had no
      previous surgery (group A) and 60 primary TKA had arthroscopic debridement (group
      B). All the patients underwent a clinical and radiological evaluation as well as
      IKS scores. Statistical analysis of postoperative complications revealed that
      group B had a higher postoperative complication rate (P < 0.01). In this group,
      30% of local complications were re-operated and 8.3% of these cases underwent
      revision TKA (P < 0.01). The mean interval between arthroscopy and primary TKA
      was 53 months. However, statistical analysis did not reveal a direct correlation
      between arthroscopy/primary TKA interval and postoperative complications/failures
      (P = 0.55). The Kaplan-Meier survival curves showed a survival rate of 98.1 and
      86.8% at 10 years follow-up for groups A and B, respectively. Our data allow us
      to conclude that previous knee arthroscopy should be considered a factor related
      to postoperative primary TKA outcomes as demonstrated by the higher rate of
      postoperative complications and failures (P < 0.001) as well as a worse survival
      curve than group A.

PMID- 19099294
TI  - Cognitive and psychomotor effects in males after smoking a combination of tobacco
      and cannabis containing up to 69 mg delta-9-tetrahydrocannabinol (THC).
AB  - RATIONALE: Delta(9)-Tetrahydrocannabinol (THC) is the main active constituent of
      cannabis. In recent years, the average THC content of some cannabis cigarettes
      has increased up to approximately 60 mg per cigarette (20% THC cigarettes). Acute
      cognitive and psychomotor effects of THC among recreational users after smoking
      cannabis cigarettes containing such high doses are unknown. OBJECTIVES: The
      objective of this study was to study the dose-effect relationship between the THC
      dose contained in cannabis cigarettes and cognitive and psychomotor effects for
      THC doses up to 69.4 mg (23%). MATERIALS AND METHODS: This double-blind, placebo
      controlled, randomised, four-way cross-over study included 24 non-daily male
      cannabis users (two to nine cannabis cigarettes per month). Participants smoked
      four cannabis cigarettes containing 0, 29.3, 49.1 and 69.4 mg THC on four
      exposure days. RESULTS: The THC dose in smoked cannabis was linearly associated
      with a slower response time in all tasks (simple reaction time, visuo-spatial
      selective attention, sustained attention, divided attention and short-term memory
      tasks) and motor control impairment in the motor control task. The number of
      errors increased significantly with increasing doses in the short-term memory and
      the sustained attention tasks. Some participants showed no impairment in motor
      control even at THC serum concentrations higher than 40 ng/mL. High feeling and
      drowsiness differed significantly between treatments. CONCLUSIONS: Response time
      slowed down and motor control worsened, both linearly, with increasing THC doses.
      Consequently, cannabis with high THC concentrations may be a concern for public
      health and safety if cannabis smokers are unable to titrate to a high feeling
      corresponding to a desired plasma THC level.

PMID- 19099295
TI  - Effects of galanin on cocaine-mediated conditioned place preference and ERK
      signaling in mice.
AB  - RATIONALE: The neuropeptide galanin and its receptors are expressed in brain
      regions implicated in the rewarding effects of natural stimuli and drugs of
      abuse. Galanin has been shown to attenuate neurochemical, physiological, and
      behavioral signs of opiate and amphetamine reinforcement. OBJECTIVE: In the
      current study, we present evidence that galanin modulates neurochemical and
      behavioral correlates of cocaine response. METHODS: Mice lacking the neuropeptide
      galanin (Gal -/-) and wild-type (Gal +/+) controls were used to analyze the
      effects of galanin in an unbiased conditioned place preference paradigm. We then
      examined cocaine-induced activation of extracellular signal-regulated kinase
      (ERK) activity as a marker of intracellular signaling in the mesolimbic
      dopaminergic pathway induced by acute cocaine administration RESULTS: Gal -/-
      mice showed significantly greater conditioned place preference at a threshold
      dose of cocaine (3 mg/kg) than Gal +/+ mice, and this was reversed by
      administration of the galanin receptor agonist galnon. Consistent with the
      results of behavioral experiments, there was a significant increase in ERK
      activation in the ventral tegmental area (VTA) and nucleus accumbens (NAc) of Gal
      -/- mice but not Gal +/+ mice following acute, systemic cocaine injection at the
      threshold dose. In the NAc, but not VTA, this effect was reversed by
      administration of galnon. CONCLUSIONS: These data, coupled with previous studies
      on the effects of morphine and amphetamine, demonstrate that galanin normally
      attenuates drug reinforcement, potentially via modulation of the mesolimbic
      dopamine system.

PMID- 19099296
TI  - Glutamatergic and GABAergic modulations of ultrasonic vocalizations during
      maternal separation distress in mouse pups.
AB  - INTRODUCTION: Dysregulation of GABAergic inhibition and glutamatergic excitation
      has been implicated in exaggerated anxiety. Mouse pups emit distress-like
      ultrasonic vocalizations (USVs) when they are separated from their dam/siblings,
      and this behavior is reduced by benzodiazepines (BZs) which modulate GABAergic
      inhibition. The roles of glutamate receptors on USVs remain to be investigated.
      MATERIALS AND METHODS: We examined the roles of glutamate receptor subtypes on
      mouse pup USVs using N-methyl-D: -aspartate (NMDA) receptor antagonists with
      different affinities [dizocilpine (MK-801), memantine, and neramexane] and group
      II metabotropic glutamate receptor agonist (LY-379268) and antagonist (LY
      341495). These effects were compared with classic BZs: flunitrazepam, bromazepam,
      and chlordiazepoxide. To assess the role of GABA(A) receptor subunits on USVs,
      drugs that have preferential actions at different GABA(A)-alpha subunits (L
      838417 and QH-ii-066) were tested. Seven-day-old CFW mouse pups were separated
      from their dam and littermates and placed individually on a 19 degrees C test
      platform for 4 min. Grid crossings and body rolls were measured in addition to
      USVs. RESULTS: Dizocilpine dose-dependently reduced USVs, whereas memantine and
      neramexane showed biphasic effects and enhanced USVs at low to moderate doses.
      The NMDA receptor antagonists increased locomotion. LY-379268 reduced USVs but
      also suppressed locomotion. All BZs reduced USVs and increased motor
      incoordination. Neither L-838417 nor QH-ii-066 changed USVs, but both induced
      motor incoordination. CONCLUSION: Low-affinity NMDA receptor antagonists, but not
      the high-affinity antagonist, enhanced mouse pup distress calls, which may be
      reflective of an anxiety-like state. BZs reduced USVs but also induced motor
      incoordination, possibly mediated by the alpha5 subunit containing GABA(A)
      receptors.

PMID- 19099297
TI  - Attenuation of basal and cocaine-enhanced locomotion and nucleus accumbens
      dopamine in cannabinoid CB1-receptor-knockout mice.
AB  - RATIONALE: Effect of cannabinoid CB1 receptor deletion on cocaine's actions is
      controversial. This is partly based on findings in CB1-receptor-knockout (CB1(-/
      )) mice with CD1 genetic background. OBJECTIVES: In the present study, we used
      CB1(-/-) mice with a C57BL/6J genetic background to further investigate the role
      of CB1 receptors in cocaine's action. MATERIALS AND METHODS: Locomotor activity
      was assessed using AccuScan locomotor chambers. Brain extracellular dopamine (DA)
      levels were measured by in vivo microdialysis and by fast-scan cyclic voltammetry
      in the nucleus accumbens (NAc). RESULTS: CB1(-/-) mice displayed a significant
      reduction in basal levels of locomotion and extracellular DA, as well as in
      cocaine-enhanced locomotion and extracellular DA, as compared to their wild-type
      (CB1(+/+)) littermates. The reduction in basal and cocaine-enhanced DA appears to
      be related to a reduction in basal DA release, not to an increase in DA
      clearance, as indicated by fast-scan cyclic voltammetry in brain slices.
      Pharmacological blockade of CB1 receptors by SR141716 inhibited locomotion and
      NAc DA release in CB1(+/+) mice. CONCLUSIONS: The present findings suggest an
      important role for CB1 receptors in mediating cocaine's behavioral and
      neurochemical effects.

PMID- 19099298
TI  - Brain ultrasonography findings in neonates with exposure to cocaine during
      pregnancy.
AB  - BACKGROUND: Cocaine exposure during pregnancy has been reported to have
      detrimental effects on the fetus. OBJECTIVE: To describe the findings on cranial
      ultrasonography (CUS) as part of a neonatal screening programme for exposed
      neonates. MATERIALS AND METHODS: The study was a semiprospective analysis of a 12
      year cohort of neonates born to mothers who had used cocaine during their
      pregnancy and who had follow-up according to a strict clinical protocol. RESULTS:
      In total, 154 neonates (78 boys, 76 girls) were included, of whom 29 (19%) were
      born preterm, and 125 (81%) were born full-term. Abnormalities on CUS were seen
      in 37 neonates (24%; 95% CI 18-31%). The abnormalities were classified as minor
      in 20 (13%; 95% CI 9-19%) and mildly abnormal in 17 (11%; 95% CI 7-17%). None of
      the infants showed severe abnormalities. The abnormalities were not associated
      with the duration or maximum amount of cocaine use during pregnancy. CONCLUSION:
      None of the infants had severe abnormalities. Detected abnormalities were not
      correlated with the duration or maximum amount of cocaine use. Given these
      findings, we feel that routine cranial ultrasonography in this population is not
      warranted.

PMID- 19099300
TI  - Alpha- and beta-tubulin from Phytophthora capsici KACC 40483: molecular cloning,
      biochemical characterization, and antimicrotubule screening.
AB  - Internal fragments of alpha- and beta-tubulin genes were generated using reverse
      transcription polymerase chain reaction (RT-PCR), and the termini were isolated
      using 5'- and 3'-rapid amplification of cDNA ends. Phytophthora capsici alpha-
      and beta-tubulin specific primers were then used to generate full-length cDNA by
      RT-PCR. The recombinant alpha- and beta-tubulin genes were expressed in
      Escherichia coli BL21 (DE3), purified under denaturing conditions, and average
      yields were 3.38-4.5 mg of alpha-tubulin and 2.89-4.0 mg of beta-tubulin, each
      from 1-l culture. Optimum conditions were obtained for formation of microtubule
      like structures. A value of 0.12 mg/ml was obtained as the critical concentration
      of polymerization of P. capsici tubulin. Benomyl inhibited polymerization with
      half-maximal inhibition (IC(50)) = 468 +/- 20 microM. Approximately 18.66 +/-
      0.13 cysteine residues per tubulin dimer were accessible to 5,5'-dithiobis-(2
      nitrobenzoic acid), a quantification reagent of sulfhydryl and 12.43 +/- 0.12
      residues were accessible in the presence of 200 microM benomyl. The order of
      preference for accessibility to cysteines was benomyl > colchicine > GTP > taxol,
      and cysteine accessibility changes conformed that binding sites of these ligands
      in tubulin were folding correctly. Fluorescence resonance energy transfer
      technique was used for high throughput screening of chemical library in search of
      antimitotic agent. There was significant difference in relative fluorescence by
      210-O-2 and 210-O-14 as compared to colchicine.

PMID- 19099299
TI  - Differences in distribution of single nucleotide polymorphisms among
      intracellular pattern recognition receptors in pigs.
AB  - Pathogens localized extracellularly or incorporated into endosomes are recognized
      mainly by Toll-like receptors, whereas pathogens and pathogen-derived molecules
      that invade into the cytoplasm of host cells typically are recognized by
      intracellular pattern recognition receptors (PRRs), such as retinoic acid
      inducible gene (RIG)-like helicases (RLHs) and nucleotide-binding oligmerization
      domain (NOD)-like receptors (NLRs). RIG-I and melanoma differentiation-associated
      gene 5 (MDA5), which belong to the RLH family, recognize viral genomic RNA,
      whereas NOD2, a member of the NLR family, responds to microbial peptidoglycans.
      These receptors may play an important role in pig opportunistic infectious
      diseases, such as pneumonia and diarrhea, which markedly impair livestock
      productivity, such that polymorphisms of these receptor genes are potential
      targets of pig breeding to increase disease resistance. Here, we report single
      nucleotide polymorphisms (SNPs) in porcine DDX58, IFIH1, and NOD2, which encode
      RIG-I, MDA5, and NOD2, respectively. Interestingly, compared with DDX58 and
      IFIH1, NOD2 abounded in nonsynonymous SNPs both throughout the coding sequence
      and in sequences encoding domains important for ligand recognition, such as
      helicase domains for RIG-I and MDA5 and leucine-rich repeats in NOD2. These
      differences in the distribution of SNPs in intracellular PRRs may parallel the
      diversity of their ligands, which include nucleic acids and peptidoglycans.

PMID- 19099301
TI  - Comparative analysis of four beta-galactosidases from Bifidobacterium bifidum
      NCIMB41171: purification and biochemical characterisation.
AB  - Four different beta-galactosidases (previously named BbgI, BbgII, BbgIII and
      BbgIV) from Bifidobacterium bifidum NCIMB41171 were overexpressed in Escherichia
      coli, purified to homogeneity and their biochemical properties and substrate
      preferences comparatively analysed. BbgI was forming a hexameric protein complex
      of 875 kDa, whereas BbgII, BbgIII and BbgIV were dimers with native molecular
      masses of 178, 351 and 248 kDa, respectively. BbgII was the only enzyme that
      preferred acidic conditions for optimal activity (pH 5.4-5.8), whereas the other
      three exhibited optima in more neutral pH ranges (pH 6.4-6.8). Na(+) and/or K(+)
      ions were prerequisite for BbgI and BbgIV activity in Bis-Tris-buffered
      solutions, whereas Mg(++) was strongly activating them in phosphate-buffered
      solutions. BbgII and BbgIII were slightly influenced from the presence or absence
      of cations, with Mg(++), Mn(++) and Ca(++) ions exerting the most positive
      effect. Determination of the specificity constants (k(cat)/K(m)) clearly
      indicated that BbgI (6.11 x 10(4) s(-1) M(-1)), BbgIII (2.36 x 10(4) s(-1) M(-1))
      and especially BbgIV (4.01 x 10(5) s(-1) M(-1)) are highly specialised in the
      hydrolysis of lactose, whereas BbgII is more specific for beta-D-(1-->6)
      galactobiose (5.59 x 10(4) s(-1) M(-1)) than lactose (1.48 x 10(3) s(-1) M(-1)).
      Activity measurements towards other substrates (e.g. beta-D-(1-->6) galactobiose,
      beta-D-(1-->4) galactobiose, beta-D-(1-->4) galactosyllactose, N
      acetyllactosamine, etc.) indicated that the beta-galactosidases were
      complementary to each other by hydrolysing different substrates and thus
      contributing in a different way to the bacterial physiology.

PMID- 19099302
TI  - Fracture-associated and idiopathic subchondral vertebral lesions: a magnetic
      resonance study in autopsy specimens with histologic correlation.
AB  - OBJECTIVE: The aim of this study was to describe and compare the magnetic
      resonance (MR) and histological appearance of subchondral vertebral lesions that
      are idiopathic or that develop with vertebral fractures. MATERIALS AND METHODS:
      T1- and T2-weighted spin-echo images and radiographs were obtained in 81
      cadaveric spine specimens. All subchondral vertebral lesions that were considered
      to be idiopathic or associated with vertebral end plate fractures were selected.
      Lesions due to growth disturbance were excluded. Radiographs and MR images were
      analyzed in consensus by two radiologists, and sampled specimens were analyzed by
      a pathologist. RESULTS: Eleven idiopathic and ten fracture-associated vertebral
      lesions were available. On T1-weighted images, all lesion signal intensity was
      low and homogeneous. On T2-weighted images, all idiopathic lesions showed a
      heterogeneous signal with a central low or intermediate signal component and a
      peripheral high or intermediate component. All but one fracture-related lesions
      showed a homogeneous intermediate to high signal intensity. Histological analysis
      of idiopathic lesions showed a central acellular fibrous connective tissue in all
      cases surrounded by loose connective tissue in nine cases. Herniated disk
      material and cartilage metaplasia were found in one lesion only. Fracture
      associated lesions contained herniated disk material, necrotic tissue, and loose
      connective tissue with a peripheral component of loose fibrovascular connective
      tissue in four cases only. CONCLUSION: MR and histological appearance of
      idiopathic and fracture-associated subchondral vertebral lesions differ,
      suggesting that they might have a different origin.

PMID- 19099303
TI  - Surgical correction of Madelung's deformity by combined corrective radioulnar
      osteotomy: 14 cases with four-year minimum follow-up.
AB  - Fourteen wrists in 11 girls, mean age 13.3 years (range 9-16) at surgery, were
      treated for Madelung's deformity. The presenting complaint was incapacitating
      pain. All were treated by radial closing wedge osteotomy and ulnar shortening
      osteotomy. The dorsal retinaculum was also surgically repaired in six cases. At a
      mean follow-up of 5.1 years (range 4-8.75), we observed improved range of motion
      in both flexion/extension and pronation/supination and absence of pain during
      daily activity. Radiographically, positioning of the distal radial articular
      surface and lunate subsidence were improved. Union was obtained after all
      osteotomies without secondary procedures. Posterior displacement of the ulnar
      head persisted in two wrists. Combined radioulnar osteotomy restored the anatomy
      to as near normal as possible. This technique provides satisfactory and
      encouraging results and does not compromise the surgical future of the wrist.
      However, longer follow-up is required to assess recurrence or possible long-term
      degenerative consequences.

PMID- 19099304
TI  - The influence of the centre of rotation on implant survival using a modular stem
      hip prosthesis.
AB  - The restoration of the hip centre of rotation in an anatomical position is
      considered to be relevant for total hip prosthesis survival. When the cup is
      implanted with a high centre of rotation, the lever arm of the abductor muscles
      is decreased, causing higher joint-reaction forces. Modular stems with varying
      lengths and geometries can be used to balance soft tissues, and ceramic bearing
      surfaces can be used to reduce the wear rate. Forty-four hip replacements
      performed with a high hip centre of rotation were matched with 44 performed with
      an anatomical centre of rotation. In all cases the preoperative diagnosis was
      dysplasia of the hip (DDH) and cementless modular neck prostheses with ceramic
      bearing surfaces were used. At nine years follow-up the mean Harris hip and WOMAC
      scores were not statistically different. All stems and cups were stable; the
      femoral offset was no different between the two groups (p = 0.4) as leg-length
      discrepancy (p = 0.25).

PMID- 19099306
TI  - A case report of successful alemtuzumab treatment of a B-CLL patient suffering
      from renal failure.

PMID- 19099305
TI  - Initial experience with custom-fit total knee replacement: intra-operative events
      and long-leg coronal alignment.
AB  - New technology using magnetic resonance imaging (MRI) allows the surgeon to place
      total knee replacement components into each patient's pre-arthritic natural
      alignment. This study evaluated the initial intra-operative experience using this
      technique. Twenty-one patients had a sagittal MRI of their arthritic knee to
      determine component placement for a total knee replacement. Cutting guides were
      machined to control all intra-operative cuts. Intra-operative events were
      recorded and these knees were compared to a matching cohort of the senior
      surgeon's previous 30 conventional total knee replacements. Post-operative
      scanograms were obtained from each patient and coronal alignment was compared to
      previous studies using conventional and computer-assisted techniques. There were
      no intra-operative or acute post-operative complications. There were no
      differences in blood loss and there was a mean decrease in operative time of 14%
      compared to a cohort of patients with conventional knee replacements. The average
      deviation from the mechanical axis was 1.2 degrees of varus, which was comparable
      to previously reported conventional and computer-assisted techniques. Custom-fit
      total knee replacement appeared to be a safe procedure for uncomplicated cases of
      osteoarthritis.

PMID- 19099307
TI  - A mathematical analysis of physiological and morphological aspects of wound
      closure.
AB  - A computational algorithm to study the evolution of complex wound morphologies is
      developed based on a model of wound closure by cell mitosis and migration due to
      Adam [Math Comput Model 30(5-6):23-32, 1999]. A detailed analysis of the model
      provides estimated values for the incubation and healing times. Furthermore, a
      set of inequalities are defined which demarcate conditions of complete, partial
      and non-healing. Numerical results show a significant delay in the healing
      progress whenever diffusion of the epidermic growth factor responsible for cell
      mitosis is slower than cell migration. Results for general wound morphologies
      show that healing is always initiated at regions with high curvatures and that
      the evolution of the wound is very sensitive to physiological parameters.

PMID- 19099308
TI  - Effects of electrical stimulation program on trunk muscle strength, functional
      capacity, quality of life, and depression in the patients with low back pain: a
      randomized controlled trial.
AB  - The aim of this clinical trial was to evaluate the effects of electrical
      stimulation (ES) program on trunk muscle strength, functional performance,
      quality of life (QOL) in the patients with chronic low back pain (CLBP). A total
      of 41 patients with definite CLBP were included in this study. These patients
      were randomized into two groups. Group 1 (n = 21) was given an ES program and
      exercises. Group 2 (n = 20) was accepted as the control group and given only
      exercises. Both the programs were performed 3 days a week, for 8 weeks in the out
      patient department. The patients were evaluated according to pain, disability,
      functional performance, endurance, quality of life, depression. The muscle
      strengths were measured with a hand-held dynamometer. There were significant
      improvements for all the parameters in two groups after the treatment. Except
      depression and social function, the improvements for all the parameters were
      better in the ES group than in the control group. We observed that ES program was
      very effective in improving QOL, functional performance and isometric strength.
      In conclusion, we can say that ES therapy provides comfortable life functions by
      improving muscle strength, functional performance and QOL.

PMID- 19099309
TI  - Surgeon's expectations do not predict the outcome of a total knee arthroplasty.
AB  - INTRODUCTION: It is fascinating for both the patient and the surgeon to predict
      the outcome of a TKA at an early stage. Satisfaction after TKA is primarily
      determined by the preoperative expectations of the patient. The purpose of this
      study was to investigate if the peri-operative expectations of the surgeon
      predicted the outcome of a TKA. PATIENTS AND METHODS: A prospective study of 53
      primary TKAs was performed. Preoperatively, the surgeon described the assessment
      of the difficulty of the TKA on a VAS. Immediately postoperative, the surgeon
      gave his satisfaction VAS about the procedure. After 1 year the surgeon's
      satisfaction VAS, the patient's satisfaction VAS and the KSCRS were determined.
      RESULTS: The Spearman's correlation coefficients between the preoperative
      difficulty assessment, the immediate postoperative satisfaction and the outcome
      measurements after 1 year were all very poor (-0.01 to 0.23). CONCLUSIONS: The
      outcome of a TKA depends on multiple factors. Both the surgeon's preoperative
      assessment of the difficulty and the surgeon's immediate postoperative
      satisfaction do not independently predict the outcome of a TKA.

PMID- 19099310
TI  - Cystic adenomatoid malformation of the lung causing hydrops fetalis: case report
      and review of the literature.
AB  - OBJECTIVE: Fetal congenital cystic adenomatoid malformation (CCAM) is a rare lung
      abnormality with a highly variable prognosis depended on the presence of fetal
      hydrops and the size of the cysts. In case of fetal hydrops the prognosis is
      fatal without intervention. METHODS AND DESIGN: Case report and literature
      review. SETTING: We report on the ultrasound and pathological findings of a
      hydropic fetus due to a CCAM Type II at 22 weeks of gestation. CONCLUSIONS:
      Congenital cystic adenomatoid malformation is a rare fetal lung disease with an
      excellent prognosis in the absence of fetal hydrops. CCAM associated with fetal
      hydrops carries a grave prognosis but survival rates of 70% can be achieved by
      thoraco-amniotic drainage in those with macrocystic lesions.

PMID- 19099311
TI  - Prophylactic bilateral oophorectomy during vaginal hysterectomy for benign
      pathology.
AB  - OBJECTIVE: The aim of this study was to assess the feasibility and safety of
      vaginal removal of ovaries at the time of vaginal hysterectomy. MATERIALS AND
      METHODS: All patients candidate to hystero-salpingo-oophorectomy by transvaginal
      approach, between 1 March 2004 and 28 February 2007, were admitted in the study.
      RESULTS: Of the 472 women included in the study, 432 (91.5%) underwent
      hysterectomy and bilateral oophorectomy by vaginal approach. There was only one
      case of major vessel injury, but no patients required blood transfusion. All the
      operations were performed only by vaginal route and no conversion to the
      abdominal route was required. CONCLUSION: The need to perform oophorectomy should
      not be considered a contraindication to vaginal hysterectomy.

PMID- 19099312
TI  - Mucinous adenocarcinoma arising in ovarian mature cystic teratoma in pregnancy.
AB  - We report a case of mucinous adenocarcinoma arising from mature cystic teratoma
      (MCT) of the ovary ascertained incidentally during pregnancy. An ovarian adnexal
      mass was seen in a 38-year-old pregnant woman during cesarean section.
      Oophorectomy revealed a mucinous adenocarcinoma arising from MCT with additional
      capsule invasion. Following this, staging procedures were applied. The patient
      was staged as IC and adjuvant chemotherapy was applied. She has remained disease
      free for over 24 months. To our knowledge, this is a case of mucinous
      adenocarcinoma arising from MCT and the third case of malignant transformation
      from MCT in pregnancy in English literature.

PMID- 19099313
TI  - Plasma sFlt-1-to-PlGF ratio is correlated with inflammatory but not with
      oxidative stress in Chinese preeclamptic women.
AB  - PURPOSE: Considerable interest has been focused on angiogenic factors and
      angiogenic imbalance in the field of pre-eclampsia (PE), owing to its gaining
      role in the development of PE. This study was addressed to investigate the
      associations of sFlt-1-to-PlGF plasma ratios with oxidative stress assessed by
      the level of 8-isoprostane, and inflammation measured by the level of high
      sensitive C-reactive protein (hs-CRP), and adipocytokines. METHODS: A total of 83
      patients with PE including 47 mild PE (MPE) and 36 severe PE (SPE) and 50 age
      matched normotensive subjects in the third trimester of pregnancy were examined.
      Measurements included body mass index (BMI), systolic and diastolic blood
      pressure (BP) levels, plasma concentrations of hs-CRP, 8-isoprostane,
      adiponectin, and leptin. RESULTS: Subjects with PE had higher levels of sFlt
      1/PlGF (P < 0.01), hs-CRP (P < 0.01), 8-isoprostane and leptin (both P < 0.01)
      and lower adiponectin (P < 0.01) than did normotensive control subjects.
      Significant positive correlations were found between plasma sFlt-1/PlGF and hs
      CRP (r = 0.437, P < 0.01) or leptin (r = 0.656, P < 0.01). A weak inverse
      correlation emerged between sFlt-1/PlGF and adiponectin (r = -0.306, P < 0.01).
      When a multiple regression analysis was performed, with sFlt-1/PlGF as a
      dependent variable and all the other parameters as independent variables, sFlt
      1/PlGF maintain a significant relationship with leptin (beta = 0.219, P < 0.05)
      and with hs-CRP (beta = 0.295, P < 0.01) as well as with systolic BP(beta =
      0.446, P < 0.05). CONCLUSIONS: In Chinese preeclamptic women, plasma sFlt-1-to
      PlGF ratio is correlated with inflammatory and adipocytokines but not with
      oxidative stress.

PMID- 19099314
TI  - The effectiveness of gabapentin on post-tonsillectomy pain control.
AB  - Postoperative pain is one of the most troublesome aspects of tonsillectomy for
      patients. Although various analgesics have been administered for pain control
      following tonsillectomy, it has still not been effectively controlled. Therefore,
      this study was conducted to evaluate the effectiveness of premedication using
      gabapentin on postoperative pain control in patients undergoing tonsillectomy. A
      total of 58 adult patients were randomly divided into a control group and a
      gabapentin group. Patients in the control group received an oral placebo
      preoperatively, whereas those in the gabapentin group received an oral dose of
      gabapentin preoperatively. All participants were provided with patient-controlled
      analgesia using fentanyl for 48 h after surgery. The total amount of fentanyl
      injected and the number of injections of dicolfenac sodium (75 mg each) requested
      by each of the group was then compared. Pain assessment was performed using a
      visual analog scale during resting periods (rVAS) and during swallowing (sVAS)
      for 9 days after the operation. The number of dicolfenac sodium injections and
      the total amount of fentanyl injected decreased significantly in the gabapentin
      group (P < 0.01). The sVAS of the gabapentin group was also significantly lower
      than that of the control group at 2 and 4 h after surgery, but there were no
      significant differences in the sVAS observed between the two groups for the
      remainder of the postoperative period. There were no significant differences in
      the rVAS observed between the two groups throughout the postoperative period.
      Thus, premedication with gabapentin decreased post-tonsillectomy pain. So the
      addition of gabapentin prior to tonsillectomy may have an adjunctive role in pain
      control.

PMID- 19099315
TI  - Use of intratympanic dexamethasone for the therapy of low frequency hearing loss.
AB  - The objective was to assess the efficacy of intratympanic dexamethasone in
      treatment of sensorineural hearing loss at lower frequencies (LFSHL). The design
      is a prospective study. Eleven female and three male patients with LFSHL were
      included in this study. They were evaluated with pure-tone audiometry, acoustic
      admittance, transient evoked otoacoustic emission, and glycerol test. Seven,
      four, and three patients were seen within the mean of 2.86 +/- 1.35 (1-5), 18.25
      +/- 2.36 (15-20), and 750 +/- 700 (60-1,460) days from onset of LFSHL,
      respectively. They were treated with daily intratympanic dexamethasone (ITD)
      injection and reviewed with repeated daily audiograms during the intratympanic
      treatment. As complementary treatment, they were given oral prednisolone 1 mg/kg
      (maximum 60 mg), with 10 mg decreasing doses for every 3 days. Results were
      compared with their unaffected ear. The mean +/- SD hearing level at 0.125 up to
      1.5 kHz improved from 64.29 +/- 19.18 to 25.93 +/- 13.54 (P < 0.001), pure tone
      average improved from 62.7 +/- 25.7 to 22.9 +/- 17.8 (P < 0.001), speech
      reception thresholds improved from 34.6 +/- 29.45 to 17.5 +/- 16.38 (P = 0.028),
      speech discrimination scores improved from 65.7 +/- 39.8 to 84.6 +/- 24.7% (P =
      0.024) with treatment. Complete recovery in 10 of 14 patients, partial recovery
      in 3 patients, was achieved after therapy; and in one patient the situation was
      unchanged. The mean hearing level at 0.125 up to 1.5 kHz was elevated from 45.6
      +/- 17.5 to 9.1 +/- 10.3 dB (P < 0.001) when compared with unaffected ear. The
      mean recovery rate was 77.9 +/- 25.3%. ITD is an effective therapy for LFSHL.

PMID- 19099316
TI  - Antrochoanal polyp: a comparative study of endoscopic endonasal surgery alone and
      endoscopic endonasal plus mini-Caldwell technique.
AB  - Antrochoanal polyp (ACP) originates in the maxillary sinus. To diminish the
      regrowth rate of choanal polyp, a complete removal of the antral portion and its
      attachment is necessary. There are several methods for this purpose, but in this
      study two techniques were comparatively investigated. This retrospective study
      was conducted by analyzing the database of 40 operated patients for ACP, 19 of
      whom underwent an endoscopic endonasal removal of polyps and 21 experienced
      endoscopic endonasal surgery with mini-Caldwell operation. The two techniques
      were compared with regard to their complications and regrowth rate. It emerged
      that post-operative complications (bleeding, synechia, ostia stenosis) in both
      groups were mild and there was not any significant difference between the two
      groups. Out of 19 cases in the endoscopic endonasal surgery group, 4 had
      recurrences, while in the mini-Caldwell group we had no recurrence. (P = 0.042)).
      This result implies that, in order to prevent incomplete excision and
      recurrences, combined approaches (endoscopic endonasal surgery and mini-Caldwell)
      should be considered, particularly when the attachment site of the antral part of
      ACP is undetected.

PMID- 19099317
TI  - The HD-Panoramic Visualization System: a new visualization system for ENT
      surgery.
AB  - This work examines the application possibilities of a new visualization system,
      the Panoramic Visualization System (HD-PVS), in ENT surgery. The Panoramic
      Visualization System (PVS) is a novel optical system that is neither an endoscope
      nor a microscope. It has a focal length of 200 mm, a wide field of view and is
      used together with an HD camera and an HD monitor (HD-PVS). The analysis of the
      visualization quality took place in laboratory conditions using 4 close-to
      surgery scenarios with altogether 40 data points. Further, the system was used on
      patients in 45 procedures (tympanoplasty, parotidectomy, neck dissection,
      septumplasty, transfacial approaches). The results were analyzed following the
      ICCAS workflow-scheme and with standardized questionnaires. In the analysis of
      the visualization quality, the PVS exhibited the best total evaluation in the lab
      test in two out of four scenarios. In one of four scenarios, the PVS as well as
      the microscope achieved the maximum attainable score. In one out of four
      scenarios, the endoscope attained a better result than the PVS. The microscope
      was never superior to the HD-PVS in terms of image quality. In four out of five
      clinical applications, the PVS was evaluated as operational with slight
      modifications. Most development is needed in middle ear surgery applications. The
      remaining procedures already benefit in the system configuration examined here,
      and they were regularly accomplished with support of the PVS. The present study
      offers a good basis for introducing the PVS to ENT surgery. The advantages over
      the existing gold standard include lower initial costs for the optical system
      than for an operating microscope since the HD-video system is often already in
      place, smaller space requirements than a microscope, equal or at times better
      visualization quality than the microscope, the possibility of videoendoscopic
      representation of surgeries in which this was impossible before, and better
      ergonomic conditions.

PMID- 19099319
TI  - The dirty war index: a public health and human rights tool for examining and
      monitoring armed conflict outcomes.

PMID- 19099320
TI  - Acute mountain sickness in children and their parents after rapid ascent to 3500
      m (Putre, Chile).
AB  - OBJECTIVE: Our objective was to determine the incidence of acute mountain
      sickness (AMS) and the cardiorespiratory responses, in children and their
      parents, after rapid ascent to 3500 m. The sample population was composed of
      children and their parents who ascended within 24 hours from Arica (sea level) to
      Putre (3500 m) in Chile. METHODS: Acute mountain sickness symptoms were evaluated
      using the Children's Lake Louise Score (CLLS) in children and the Lake Louise
      Scoring System in their parents. Heart rate, pulse oximetry, and AMS symptoms
      were evaluated in Arica before ascent, in Putre, and on return to Arica. RESULTS:
      The mean CLLS was 10.8 +/- 3 at Putre, with 92% of children developing AMS. Low
      oxygen saturation (80% +/- 2%) and tachycardia (129 +/- 9 beats/min) were
      observed in children with higher AMS scores. In contrast, parents had higher
      oxygen saturation (89% +/- 3%), less tachycardia (87 +/- 13 beats/min), and a 25%
      incidence of AMS. CONCLUSIONS: Our results indicate that children exposed acutely
      to high altitude are more sensitive to hypobaric hypoxia than are their parents,
      as manifested by symptoms of AMS, significant oxyhemoglobin desaturation, and
      tachycardia. Young children may experience an exaggerated hypoxemic response to
      high altitude exposure, and young age may be an additional risk factor for the
      development of AMS.

PMID- 19099321
TI  - Tick talk: unusually severe case of tick-borne relapsing fever with acute
      respiratory distress syndrome--case report and review of the literature.
AB  - Borrelia hermsii causes tick-borne relapsing fever (TBRF) in the Pacific
      Northwest. There are few reports of TBRF-associated acute respiratory distress
      syndrome. One such unusually severe case is described. Literature is reviewed
      including diagnosis, treatment, and prevention.

PMID- 19099322
TI  - A case of elevated liver function tests after crown-of-thorns (Acanthaster
      planci) envenomation.
AB  - The crown-of-thorns starfish (Acanthaster planci) inhabits coral reefs, largely
      throughout the Indo-Pacific region. Its dorsal surface is covered with stout
      thorn-like spines. When handled or stepped on by humans, the spines can puncture
      the skin, causing an immediate painful reaction, followed by inflammation and
      possible infection. Initial pain and swelling may last for days. Effects of
      envenomation on the liver have been demonstrated previously in animal models, but
      hepatic toxicity has not previously been described in humans. We describe
      elevated liver enzymes in a 19-year-old female associated with A planci spine
      puncture wounds. To our knowledge, this is the first documented report of
      transaminitis in a human after A planci envenomation.

PMID- 19099323
TI  - Return to mountain sports after minimally invasive two-incision hip arthroplasty.

PMID- 19099324
TI  - Ondansetron for the treatment of nausea associated with altitude sickness.

PMID- 19099325
TI  - Trekkers' awareness of acute mountain sickness and acetazolamide.

PMID- 19099326
TI  - Manual assessment of the initial fall in blood pressure after orthostatic
      challenge at high altitude.
AB  - OBJECTIVE: Dizziness is a symptom of acute mountain sickness (AMS). This study
      tested whether immediate fall in systolic blood pressure (BP) on standing was
      more severe at altitude and whether this was associated with symptoms of
      dizziness. METHODS: Eighty-five lowlanders flew into La Paz, Bolivia (3650 m),
      and after 4 to 5 days of acclimatization ascended in 90 minutes to the Chacaltaya
      Laboratory (5200 m) by road. Blood pressure was measured on 5 occasions, 3 times
      at 5200 m and twice at sea level, before and after the expedition using a mercury
      sphygmomanometer. Both a supine and an erect (within 15 seconds of standing) BP
      measurement were recorded. Participants recorded whether they felt dizzy on
      standing. A mixed-effect model was used to test for a difference in the change in
      BP for time and altitude. RESULTS: The immediate fall in systolic BP observed on
      standing was significantly greater (P < .001) on all 3 altitude study days (18.2,
      23.4, and 20.7 mm Hg) than at sea level (12.2 and 12.4 mm Hg). There was no
      significant difference in the change in diastolic BP or change in mean arterial
      BP between sea level and altitude. CONCLUSIONS: The immediate drop in systolic BP
      observed on standing was greater at altitude. However, mean arterial pressure was
      maintained, and we found no association between the degree of immediate fall in
      BP and dizziness or AMS.

PMID- 19099327
TI  - Hypothermia and other cold-related morbidity emergency department visits: United
      States, 1995-2004.
AB  - OBJECTIVE: Although hypothermia is preventable, little has been published on its
      epidemiology. This study estimates the incidence of hypothermia and other cold
      related morbidity emergency department (ED) visits in the United States. METHODS:
      We identified hypothermia and other cold-related morbidity ED visits from the
      1995- 2004 National Hospital Ambulatory Medical Care Surveys using the
      International Classification of Diseases, Ninth Revision (991.6-991.9) or cause
      of-injury E-codes (901.0-901.9 and 988.3). RESULTS: In the United States there
      were an estimated 15 574 (95% CI = 9 103-22 045) hypothermia and other cold
      related morbidity ED visits during 1995 to 2004. Compared with other ED patients,
      those with hypothermia and other cold-related morbidity diagnoses were older
      (mean age 45 vs 36 years; P = .009) and were more likely to be uninsured (risk
      ratio [RR] = 2.44; 95% CI = 1.54-3.84). Hypothermia and other cold-related
      morbidity ED visits required more transfers to critical care units (RR = 6.73;
      95% CI = 1.8-25.0) than did other ED visits. CONCLUSIONS: Hypothermia and other
      cold-related morbidity is a preventable resource-intensive condition that tends
      to affect the disadvantaged.

PMID- 19099328
TI  - The influence of ethnicity on thermoregulation after acute cold exposure.
AB  - OBJECTIVE: It is well established that a combination of factors, including
      ethnicity, may influence an individual's response to cold stress. Previous work
      from our laboratory has demonstrated that when faced with a cold challenge, there
      is a similar response in heat production between Caucasian (CAU) and African
      American (AA) individuals that is accompanied by a differential response in core
      temperature. The objective of this study was to evaluate the influence of
      ethnicity (CAU vs AA) on the thermoregulatory response after acute cold exposure
      (ACE-REC, 25 degrees C air). METHODS: Five AA males (20.8 +/- 0.5 years) and 10
      CAU males (25.6+/-4.9 years) underwent pre-experimental testing to determine
      Vo(2max) (AA = 37.2 +/- 0.1 mLxkg(-1)xmin(-1), CAU = 44.3 +/- 8.7 mLxkg(-1)xmin(
      1)) and body composition (AA = 14.6 +/- 5.4%, CAU = 19.2 +/- 5.0%). Participants
      underwent acute cold exposure that consisted of 120 minutes of exposure to 10
      degrees C air (ACE) followed by 120 minutes of recovery in 25 degrees C air (ACE
      REC). Rectal temperature (T(re)) was measured via a rectal thermistor. Mean skin
      temperature (T(sk)) was assessed with thermistors. Oxygen consumption (Vo(2)) was
      assessed via indirect open circuit spirometry. Rectal temperature and T(sk) were
      measured continuously, and if T(re) < or = 35 degrees C, testing was terminated.
      RESULTS: Analysis of variance for ACE-REC revealed a significant main effect for
      T(sk) across time (P < .001), T(re) across time (P < .001), and Vo(2) across time
      (P < .001). In addition, a significant time x ethnicity interaction was revealed
      for T(re) (P = .008), T(sk) (P = .042), and Vo(2) (P = .019) during ACE-REC.
      CONCLUSIONS: Based on these data, there is a differential response between CAU
      and AA across time for Vo(2), T(re), and T(sk) ACE-REC.

PMID- 19099329
TI  - Epidemiology of mountain search and rescue operations in Banff, Yoho, and
      Kootenay National Parks, 2003-06.
AB  - OBJECTIVE: To describe the epidemiology of mountain incidents and mountain rescue
      operations occurring in Banff, Yoho, and Kootenay National Parks between 1
      January 2003 and 31 December 2006. METHODS: Retrospective review of Banff, Yoho,
      and Kootenay Public Safety Occurrence Reports detailing rescue operations within
      the study period. Demographics, activity, reason for rescue, mode of rescue, type
      of injury, and fatalities were analyzed. RESULTS: A total of 317 emergency
      mountain rescue operations involving 406 persons was documented. The mean age of
      the rescued population was 35.2 years, and this population was predominantly male
      (63.1%). Hikers were involved in 43.5% of incidents, and 'slips and falls' were
      responsible for 50.2%. Helicopter was the mode of rescue in 64% of cases. Almost
      half (40.7%) of all rescues involved people with no injuries. The limbs were the
      most common body part affected (68% of traumatic injuries). Forty fatalities
      occurred-45% due to avalanches and 27.5% due to slips and falls. CONCLUSIONS:
      This study offers a synopsis of the rescue service provided by Parks Canada
      Rescue in the study area. Further work is needed to separate primary and
      contributory causes of mountain incidents, and this can be achieved by use of
      better data collection methods. Hospital follow-up is required to accurately
      assess the morbidity and mortality associated with mountain incidents. Data
      presented are expected to be of value to a variety of tourism, health, and safety
      organizations.

PMID- 19099330
TI  - Physiological responses to graded acute normobaric hypoxia using an intermittent
      walking protocol.
AB  - OBJECTIVE: The study aimed to examine the physiological responses to acute
      normobaric hypoxia during an intermittent walking protocol. METHODS: Twelve
      active healthy male participants completed a 125-minute test that involved rest
      and walking (50% VO(2max)) during normoxic (20.93%O(2)) and 2 hypoxic conditions
      (14%O(2) and 12%O(2)). A range of physiological markers were measured throughout
      the test. Lake Louise Questionnaire scores and Environmental Symptoms
      Questionnaire cerebral scores were used as a measurement of acute mountain
      sickness symptoms. RESULTS: Oxygen saturation, thermal sensation scale, heart
      rate, perceived thirst, core temperature, rating of perceived exertion, feeling
      state, and Deltabody mass all positively correlated with the highest Lake Louise
      Questionnaire and Environmental Symptoms Questionnaire cerebral scores (P < .05)
      and were significantly different between the 3 conditions during the exercise
      phases. CONCLUSION: A range of physiological markers are associated with symptoms
      of acute mountain sickness following brief periods of hypoxic exposure.

PMID- 19099331
TI  - Update on high-altitude pulmonary edema: pathogenesis, prevention, and treatment.
AB  - High-altitude pulmonary edema (HAPE) is a life-threatening noncardiogenic form of
      pulmonary edema (PE) that afflicts susceptible persons after rapid ascent to high
      altitude above 2500 m. Its pathogenesis is related to increased sympathetic tone,
      exaggerated hypoxic pulmonary vasoconstriction, uneven hypoxic pulmonary
      vasoconstriction with overperfusion of some regions of the pulmonary vascular
      bed, increased pulmonary capillary pressure, stress failure of pulmonary
      capillaries, and alveolar fluid leak across capillary endothelium resulting in
      interstitial and alveolar edema. Prevention of HAPE is most effectively achieved
      by gradual ascent with time for acclimatization, although recent small studies
      have highlighted a number of pharmacologic options. Inhaled salmeterol prevents
      HAPE presumably by increasing alveolar fluid clearance, the phosphodiesterase-5
      inhibitor tadalafil works by acting as a pulmonary vasodilator, and dexamethasone
      seems to prevent HAPE by stabilizing the capillary endothelium, along with other
      potential effects. These investigations have yet to be validated in widespread
      clinical practice. Nifedipine, which prevents HAPE via its effects as a pulmonary
      vasodilator, has a longer history of clinical use. The most effective and
      reliable treatment of established HAPE is immediate descent and/or adequate flow
      supplemental oxygen to maintain arterial saturation above 90%, accompanied by
      rest from strenuous physical activity. Use of a portable hyperbaric chamber is an
      effective temporizing measure, and nifedipine may be used for treatment of HAPE,
      although only as an adjunct to descent and/or supplemental oxygen if these
      methods of treatment are not immediately available to a person with HAPE.

PMID- 19099332
TI  - Introduction to organizing wilderness medicine on a regional scale.

PMID- 19099334
TI  - Splenic infarction in a high-altitude traveler with undiagnosed sickle cell
      trait.

PMID- 19099335
TI  - Dysesthesias of the hands and feet after visiting Lhasa, Tibet.

PMID- 19099336
TI  - Survey of public knowledge and responses to educational slogans regarding cold
      water immersion.
AB  - OBJECTIVES: Cold water temperature is a significant factor in North American
      drownings. These deaths are usually attributed to hypothermia. Survey questions
      were administered to 661 attendees of cold-stress seminars-including medical,
      rescue, law enforcement and lay attendees-to determine general knowledge of the
      effects of ice water immersion and responses to 2 public service educational
      slogans. METHODS: Five questions were posed at the beginning of seminars to 8
      groups (ranging in size from 46 to 195) during a 2-year period. Pi(2) analyses
      were used to determine if responses within any occupational category differed
      from the group responses. RESULTS: A high portion of respondents greatly
      underestimated the time to become hypothermic in ice water (correct answer >30
      minutes; 84% stated 15 minutes or less) and the time until cooling was life
      threatening (correct answer >60 minutes; 85% stated 30 minutes or less). There
      were no occupational differences in these responses. Most of the respondents
      identified a correct cause of death during cold stress (81% stated cardiac
      arrest, hypothermia, or drowning). Although both educational slogans had some
      advantages, between 40% (Slogan #1) to 50% (Slogan #2) of respondents did not
      respond correctly. CONCLUSIONS: The majority of respondents underestimated the
      time available for survival during ice water immersion. It is important to
      educate the public accurately to decrease the probability of panic under these
      circumstances. More work is required to develop effective educational slogans
      that provide proper information and actions for victims of cold-water immersion.

PMID- 19099337
TI  - A locally developed snakebite management protocol significantly reduces overall
      anti snake venom utilization in West Bengal, India.
AB  - OBJECTIVE: The purpose of this study was to determine the impact of a nationally
      developed snakebite treatment protocol on the amount of anti snake venom (ASV)
      used in treating snakebites in a developing country and its effect on mortality.
      In addition, basic epidemiology data were collected and analyzed. METHODS:
      Experts in Indian snakebites developed a protocol specifically designed for
      snakebite treatment in India. A training program was implemented in Midnapore
      Medical College in West Bengal, India, under the direction of the Health Minister
      to train care providers in the new protocol. After training, data were collected
      for 839 snakebite victims over a 12-month period and included epidemiological
      data, ASV volumes administered, and mortality. The results were collated and
      compared with results calculated from 780 snakebite victims treated during the 12
      month period before implementation of the protocol. Treatment prior to protocol
      implementation was based on knowledge gained by the care providers from western
      and forensic medicine textbooks. RESULTS: Protocol-guided treatment resulted in a
      66% decline in the amount of ASV administered to victims. Fewer victims received
      ASV based on rational guidelines for assessing envenomation, dosage and repeat
      dosage, and clear endpoints to ASV therapy. In addition, there was a trend
      towards reduced mortality and an absolute reduction of 24%. CONCLUSION: Use of
      the protocol reduced ASV utilization and the number of deaths. Locally developed
      protocols should be encouraged by such organizations as the World Health
      Organization and national and state governments and should be established with
      significant input from local experts.

PMID- 19099338
TI  - Organizing wilderness medicine on a regional scale.

PMID- 19099341
TI  - Assessing both genetic variation (SNPs/CNVs) and gene-environment interactions
      may lead to personalized gastric cancer prevention.

PMID- 19099340
TI  - Improving trauma care in rural Iran by training existing treatment chains.
AB  - INTRODUCTION: Iran has a major land mine injury problem in its border areas. Mine
      injuries have a high mortality and morbidity, and the injuries generally occur in
      remote areas. Iran has a well developed system of rural health workers and
      clinics, covering most border areas. These have mainly had prevention,
      immunization and curative treatment for medical conditions as their focus. We
      hypothesized that adding a short training in trauma care to the already existing
      system of rural health workers would improve the care for trauma victims. The
      objective of the present study was to describe the training and evaluate its
      effect using mortality and change in physiological function of victims after
      prehospital treatment as outcome measures. METHODS: The training was arranged in
      villages and clinics in the border area. Physicians, nurses and emergency
      technicians from a local emergency clinic, the Mehran Clinic, were given a two
      day course with monthly refreshers; while rural healthcare workers and lay people
      were given shorter training courses in their villages. All patients treated were
      registered and patients were followed up. Physiological changes after treatment
      was assessed with a modified three-component 'revised trauma score'. Patients
      entered the system directly through the local emergency clinic (some with
      prehospital treatment before arriving at the local emergency clinic). Some were
      transferred to the referral university hospital, and there they could be compared
      with a convenience comparison group of patients transported directly to the
      referral university hospital without treatment during transportation. RESULTS:
      During the three-year study period 109 physicians, nurses and 76 emergency
      technicians (behwarses) were trained, while 4649 lay persons had first-responder
      training. A total of 366 patients were treated by the system. Prehospital support
      was given to 238 victims before admission to the primary clinic. We found no
      difference in mortality between patients with and without first-responder
      treatment. In all, 226 of these patients were transferred to the university
      hospital. During the period a group of 245 other victims of injury was admitted
      directly to the university hospital. The physiological status of the transferred
      victims improved significantly by treatment from the emergency clinic to the
      university hospital with a mean improvement in the Physiological Severity Score
      (PSS) of 1.11 (95% CI 0.98-1.24). The PSS of the intervention group was
      significantly higher than the status of the group brought directly to the
      university hospital without treatment during transportation (difference 0.73, 95%
      CI difference 0.55-.91, p < 0.0005). CONCLUSIONS: We found that the existing
      rural healthcare system in Iran's western border area could be upgraded to care
      for mine victims and victims of other injuries by using available resources. This
      system improved the physiological status of the victims during transportation,
      and was able to handle penetrating as well as blunt injury. The use of existing
      health structures should be considered when planning improvements.

PMID- 19099342
TI  - Inflammatory bowel disease classification through multigene analysis: fact or
      fiction?

PMID- 19099344
TI  - PCR Perfection: insider tricks.
AB  - PCR Perfection: insider tricks was a 1-day symposium on the actual design methods
      of PCR assays. This day primarily focused on different design methodologies for
      ensuring an optimal PCR reaction.

PMID- 19099345
TI  - Improved molecular diagnostic tools for human hookworms.
AB  - Blood-feeding hookworms are parasitic roundworms (i.e., nematodes) of major
      socioeconomic importance, affecting millions of people worldwide. Despite their
      impact on human health, little attention has been paid to improving practical
      methods of diagnosis. The genetic characterization of hookworms and specific
      diagnosis of their infections are central to elucidating the ecology and
      epidemiology of these parasites as well as the control of the disease they cause.
      Traditional coprodiagnostic methods have major limitations. This article
      summarizes progress in the development of molecular-analytical and -diagnostic
      tools, and discusses the need to establish practical 'laboratory' and 'field'
      assays for use in integrated hookworm prevention and control programs.

PMID- 19099346
TI  - Molecular diagnosis of Fragile X syndrome.
AB  - Fragile X syndrome, the most prevalent inherited cause of mental retardation, is
      related to hyperexpansion of a polymorphic CGG repeat of the FMR1 gene. Expansion
      of 55-200 repeats are called premutations and characterize carriers who usually
      have no mental impairment. The disease causing full mutations exceed 200 CGG
      repeats, are hypermethylated and lead to transcriptional silencing of the gene
      and absence of the Fragile X mental retardation protein (FMRP). Diagnostic
      approaches involve molecular and immunocytochemical techniques. Southern blot,
      which allows mutations to be detected and methylation status to be determined in
      a single test, remains the procedure of choice for most laboratories.
      Modifications of PCR methods, including methylation specific PCR, are also
      proposed but their implementation is still in question because of inherent
      difficulties to amplify CGG repeats, distinguish between mosaic patterns and
      interpret results in female individuals. The FMRP antibody test is also suitable
      for large population screening and elucidation of Fragile X syndrome cases with
      no CGG expansion, but it is not widely applied. In search for novel diagnostic
      approaches, use of PCR as a first prescreening test followed by Southern blot is
      considered the most reliable procedure.

PMID- 19099347
TI  - Capsule endoscopy in the evaluation and management of inflammatory bowel disease:
      a future perspective.
AB  - Wireless capsule endoscopy (WCE) has emerged as an important diagnostic tool for
      the evaluation of patients with suspected small intestinal (SI) disease,
      including obscure gastrointestinal bleeding, Crohn's disease (CD), malabsorptive
      disorders and SI tumors. Since a great number of patients with CD have small
      bowel (SB) involvement, it is important for newly diagnosed patients to undergo
      an evaluation of the SB, which has traditionally been performed using a
      radiographic study such as a SB follow-through. The greatest utility of WCE in
      the evaluation of SB CD has been observed in cases of suspected CD, where the
      initial evaluation with upper and lower endoscopy as well as traditional
      radiographic techniques have failed to establish the diagnosis. WCE can detect SB
      involvement in CD, particularly early lesions that can be overlooked by
      traditional radiological studies. The sensitivity of diagnosing SB CD by WCE is
      superior to other endoscopic or radiological methods such as push enteroscopy,
      computed tomography or magnetic resonance enteroclysis. The utility of WCE in
      patients with known CD, indeterminate colitis and a select group of patients with
      ulcerative colitis can help to better define the diagnosis and extent of the
      disease, and assist in the management of patients with persistent symptoms. A
      disadvantage of WCE is that the device may be retained in a strictured area of
      the SB, which may often be present in patients with CD, in addition to a lower
      specificity. WCE may replace classical studies and become the gold standard for
      diagnosing SB involvement in patients with suspected, or known CD, in the absence
      of strictures and fistulae.

PMID- 19099348
TI  - Placentation abnormalities in the pathophysiology of preeclampsia.
AB  - Preeclampsia, a pregnancy-specific syndrome of hypertension and proteinuria, is
      one of the leading causes of perinatal morbidity and mortality. Although the
      initiating factor is unknown, a clearer picture regarding the network mechanisms
      of preeclampsia has begun to emerge during the past few years. The pathogenesis
      of preeclampsia can be described as having two stages. The first stage of
      preeclampsia involves abnormal placental implantation, followed by transition to
      the second stage of endothelial dysfunction. The link bridging these two stages
      is considered to be oxidative stress and disrupting angiogenesis. Discovery of
      the fundamental molecular mechanisms causing preeclampsia may provide a potential
      for prophylactic intervention and symptom amelioration. In this article, the
      clinical syndrome and risk factors of preeclampsia will be introduced, followed
      by the recent advances in our understanding of the pathophysiology of
      preeclampsia and, finally, research into aberrant placentation will be discussed.

PMID- 19099349
TI  - Human chorionic gonadotropin and associated molecules.
AB  - When considering human chorionic gonadotropin (hCG) and hCG tests, it is
      important to realize that it is not a single biological molecule. The regular
      form of hCG produced by differentiated syncytotrophoblast cells (regular hCG) is
      a hormone made with the primary function of maintaining the myometrial and
      decidual spiral arteries and the vascular supply of the placenta during the full
      course of pregnancy. Hyperglycosylated hCG (hCG with double-size O-linked
      oligosaccharides) is made by undifferentiated cytotrophoblast cells. This is an
      autocrine hormone with separate functions, it maintains invasion as in
      implantation of pregnancy and malignancy in gestational trophoblastic diseases. A
      hyperglycosylated free beta-subunit is produced by a high proportion of all
      malignancies. This functions as an autocrine hormone to promote the growth and
      invasion of the malignancy. It is important to realize when ordering an hCG test
      what you are measuring and whether the test ordered will detect appropriately
      these three variant of hCG as well as their degradation products. Most automated
      commercial laboratory tests, point-of-care test and over-the-counter tests are
      limited in what is detected, focusing only on regular hCG. This is in part due to
      the US FDA, who only consider hCG as a pregnancy test, and to whom only detection
      of regular hCG is critical. This may be a cause of test errors since primarily
      hyperglycosylated hCG is produced in early pregnancy, choriocarcinoma and germ
      cell testicular malignancies, and only free beta-subunit may be produced in other
      germ cell malignancies (all applications for hCG test). The exceptions are the
      older style hCGbeta radioimmunoassay and the Siemen's Immulite platform hCG test
      which detect all variant and their degradation product appropriately. Regardless
      of test specificity limitations, assays for hCG variants are widely used
      clinically in pregnancy detection, early pregnancy detection, prediction of
      spontaneously aborting and ectopic pregnancies and prediction of trisomy
      pregnancies. hCG tests are essential in managing gestational trophoblastic
      diseases, whether hydatidiform mole, invasive mole or choriocarcinoma, and are
      very useful in management of testicular malignancies and other germ cell
      malignancies.

PMID- 19099350
TI  - Management of metastatic renal cell carcinoma: current trends.
AB  - Renal cell carcinoma is one of the common malignancies of the genitourinary
      tract. In approximately one third of patients, distant metastases are present at
      the time of initial diagnosis and in another third, the tumor will recur even
      after nephrectomy with a curative intent. Renal cell carcinoma is resistant to
      all conventional treatment modalities of cancer, including radiotherapy and
      chemotherapy. We review the management of patients with metastatic renal cell
      carcinoma in the era of the new targeted therapeutic agents.

PMID- 19099351
TI  - Th2 cells as targets for therapeutic intervention in allergic bronchial asthma.
AB  - Th2 cells play a central role in the pathogenesis of allergic bronchial asthma,
      since each of their characteristic cytokines such as IL-4, IL-5, IL-9 and IL-13
      contributes to hallmarks of this disease, including airway eosinophilia,
      increased mucus production, production of allergen-specific IgE and development
      of airway hyper-responsiveness. Therefore, these cells are predisposed as target
      cells for therapeutic intervention. Experimental approaches targeted Th2-type
      effector cytokines, Th2-cell recruitment and Th2-cell development. Another
      strategy uses the immunomodulatory potential of tolerance-inducing cytokines such
      as IL-10 or of cytokines such as IL-12, IL-18 and IFN-gamma that are able to
      induce a counterbalancing Th1 immune response.

PMID- 19099353
TI  - Observation of an amorphous calcium carbonate precursor on a stearic acid
      monolayer formed during the biomimetic mineralization of CaCO(3).
AB  - The Langmuir monolayer is widely regarded as a model for investigating
      biomineralization on biological membranes, but so far the crystallization process
      has been elusive. In this work, we study the crystallization process of CaCO(3)
      on a stearic acid monolayer at the air-water interface by in situ Brewster angle
      microscopy and ex situ electron microscopy. It is shown that the final CaCO(3)
      crystals are transformed from a particle precursor rather than directly from the
      solvated ions under the compressed stearic acid monolayer. SEM and TEM images
      reveal that the precursors are uniform spherical particles of amorphous calcium
      carbonate (ACC) with sizes smaller than 100 nm. The amorphous particles are
      produced in an early stage of mineralization and can be stabilized for at least
      0.5 h. Subsequently, the ACC particles tend to aggregate with increasing
      population and are eventually transformed into the crystalline calcite phase with
      the elapse of time. This work is the first to clarify the crystallization process
      of calcium carbonate under the monolayer at the air-water interface by a direct
      observation of the ACC and therefore establish the roles of stearic acid in the
      process.

PMID- 19099354
TI  - Molecular simulations for adsorptive separation of CO2/CH4 mixture in metal
      exposed, catenated, and charged metal-organic frameworks.
AB  - The adsorption and separation of CO2/CH4 mixture are studied using molecular
      simulations in a series of metal-organic frameworks (MOFs) with unique
      characteristics such as exposed metals (Cu-BTC, PCN-6' and PCN-6), catenation
      (IRMOF-13 and PCN-6), and extraframework ions (soc-MOF). Because of the strong
      affinity with the framework, CO2 is preferentially adsorbed over CH4 in all MOFs.
      Framework catenation leads to constricted pores and additional adsorption sites
      and enhances the interaction with the adsorbate. Therefore, catenated IRMOF-13
      and PCN-6 exhibit a greater extent of adsorption, particularly for CO2, at low
      pressures than IRMOF-14 and PCN-6'; however, the opposite is true at high
      pressures. CO2/CH4 selectivity in IRMOF-1 and IRMOF-14 is almost constant at low
      pressures and increases with increasing pressure. As a result of a counterbalance
      between energetic and entropic effects, the selectivity in IRMOF-13 initially
      decreases at low pressures and then increases with pressure and finally
      approaches a constant value. Catenated MOFs have a higher selectivity than their
      non-catenated counterparts. The presence of electrostatic interaction between CO2
      and the framework leads to an increase in CO2 adsorption and a corresponding
      decrease in CH4 adsorption and consequently enhanced selectivity. In charged soc
      MOF, the extraframework NO3- ions are identified to be equally distributed from
      the nearest metal atoms and vibrate around the favorable sites. The selectivity
      in soc-MOF is substantially higher than in the other IRMOFs and PCNs and is the
      highest among various MOFs reported to date. The simulation results reveal that
      the selectivity of CO2 over CH4 in MOFs is enhanced slightly by exposed metals,
      catenation, and significantly by extraframework ions and that charged MOFs are
      promising candidates for the separation of CO2/CH4 mixture.

PMID- 19099355
TI  - Are host characteristics or exposure factors mainly involved in the acquisition
      of zoonotic Salmonella and Campylobacter coinfection in humans?
AB  - We hypothesized that patients coinfected with zoonotic Salmonella and
      Campylobacter were frailer than monoinfected Salmonella or Campylobacter
      patients. The study cohort included all first-time Salmonella/Campylobacter
      infections in Aarhus and North Jutland counties, Denmark, from 1991 through 2003.
      Data on comorbidity, hospitalization in relation to the Salmonella/Campylobacter
      infection, and 1-year mortality were obtained from electronic registries. Among
      13,449 individuals, 114 (0.85%) had Salmonella/Campylobacter coinfection, 6567
      (48.8%) had Salmonella monoinfection, and 6768 (50.3%) had Campylobacter
      monoinfection. There were no major differences in age, gender, comorbidity,
      hospitalization rates, 1-year mortality, or seasonal variation between coinfected
      patients on the one hand and each of the monoinfected patient groups on the
      other. The main difference was encountered between the Salmonella serotype
      distribution as 49.1% of coinfected patients versus 20.3% of monoinfected
      Salmonella patients had Salmonella serotypes other than Salmonella Enteritidis
      and Salmonella Typhimurium (odds ratio [95% confidence interval]: 4.07 [2.73
      6.06]). In conclusion, Salmonella/Campylobacter coinfected patients were not
      frailer than monoinfected patients. The difference in Salmonella serotype
      distribution was compatible with a higher proportion of coinfections acquired
      during foreign travel.

PMID- 19099356
TI  - Foodborne pathogens and microbiological characteristics of raw milk soft cheese
      produced and on retail sale in Brazil.
AB  - The consumption of raw milk soft cheeses (RMSC), which are typically manufactured
      in small dairy farms under unsatisfactory hygiene conditions, is common in
      Brazil. Due to these production characteristics, this type of cheese is a
      potential carrier of pathogenic microorganisms, such as Listeria monocytogenes,
      Salmonella, and enterotoxin-producing Staphylococcus spp. Considering these
      characteristics, in this work, we aimed to detect the presence of these
      pathogenic microorganisms in RMC and to evaluate their microbiological quality.
      Fifty-five samples of this product were collected from different noninspected
      commercial establishments and submitted to the enumeration of mesophilic aerobes
      (MA), total coliforms (TC), Escherichia coli, and coagulase-positive
      staphylococci (CPS), and detection of L. monocytogenes and Salmonella spp. All
      analyzed samples were negative for Salmonella spp. and L. monocytogenes. All
      samples presented counts of MA higher than 10(6) colony forming units/g (CFU/g;
      range, 3.0x10(6) to 4.0x10(9)). TC were present at levels between 1.0x10(3) and
      1.8x10(8) CFU/g, and E. coli between 1.0x10(2) and 3.5x10(6) CFU/g. CPS were
      detected in 17 (30.9%) samples at levels higher than 10(4) CFU/g. These results
      confirm the poor microbiological quality of raw milk used in the manufacturing of
      RMC samples, and also the inadequate production conditions. Therefore, the
      evaluation of microbiological safety and quality of these products must be
      constantly reported to alert the official agencies about the significance of
      proper inspection.

PMID- 19099357
TI  - Prevalence and antimicrobial resistance among Campylobacter spp. in Louisiana
      retail chickens after the enrofloxacin ban.
AB  - Effective in September 2005, enrofloxacin, a fluoroquinolone group antimicrobial,
      was withdrawn from use in the U.S. poultry farms. In this 1-year study initiated
      in October 2006, we isolated and characterized Campylobacter spp. from Louisiana
      retail conventionally raised (n = 141) and organic (n = 53) chickens as a
      comparison to evaluate the postban bacterial resistance to antimicrobials.
      Campylobacter was present in 43.3% of the chickens; similar rates were observed
      among conventional and organic chickens. A total of 165 Campylobacter isolates
      were recovered, with Campylobacter jejuni being the predominant species (66.7%).
      No apparent seasonal trend was deduced from the prevalence data. Further, the two
      main conventional and one organic chicken brands did not carry significantly
      different rates of Campylobacter (p > 0.05). The most common resistance observed
      was to tetracycline (31.5%), followed by erythromycin (20%) and ciprofloxacin
      (6.1%). No resistance to gentamicin was identified. All Campylobacter isolates
      recovered from organic chickens (n = 48) were susceptible to ciprofloxacin,
      compared to 8.5% resistance rate for those from conventional chickens (n = 117).
      Additionally, the resistance rate to erythromycin was significantly higher in
      Campylobacter isolates from conventional chickens (23.9%) than those from organic
      chickens (10.4%; p < 0.05). Our results demonstrated a low prevalence and low
      ciprofloxacin resistance rate of Campylobacter in Louisiana retail chickens after
      the enrofloxacin ban. Further studies involving a larger sample size over time
      are warranted to better assess the effects of banning enrofloxacin use in poultry
      and the levels of fluoroquinolone-resistant Campylobacter.

PMID- 19099358
TI  - Characterization of antimicrobial resistance in Salmonella enterica serotype
      Heidelberg isolated from food animals.
AB  - Fifty-eight Salmonella enterica serovar Heidelberg isolates isolated from food
      animals were tested for antimicrobial susceptibilities and further characterized
      for select antimicrobial resistance genes, plasmid carriage, class 1 integrons,
      and genetic relatedness using pulsed-field gel electrophoresis (PFGE). Seventy
      two percent of isolates displayed resistance to at least one of the antimicrobial
      agents tested, while 24% exhibited resistance to eight or more antimicrobial
      agents. Resistance was most commonly observed to tetracycline (71%), streptomycin
      (62%), and kanamycin (52%). Isolates obtained from cattle and swine displayed the
      highest rates of resistance while isolates from chickens more often displayed
      susceptibility to the tested antimicrobials. When resistance was detected, a
      corresponding resistance gene was detected in 97.3% of the isolates. Thirteen
      percent of the isolates contained class 1 integrons containing at least one
      resistance gene, most often either the aadA or dhfrA genes, which are often
      associated with resistance to streptomycin and trimethoprim, respectively. Twenty
      isolates contained plasmids estimated to be at least 75 kb in size, 17 of which
      exhibited resistance to five or more antimicrobial agents. Thirty PFGE patterns
      were generated among the 58 isolates tested using XbaI, indicating extensive
      heterogeneity among this serotype across different animal origins. Results
      confirm the presence of multidrug-resistance (MDR) phenotypes among food animal
      isolates of serovar Heidelberg, especially those obtained from mammalian species.
      The observed MDR was typically associated with the presence of large plasmids.

PMID- 19099359
TI  - Characterizing metabolic inhibition using electrochemical enzyme/DNA biosensors.
AB  - Studies of metabolic enzyme inhibition are necessary in drug development and
      toxicity investigations as potential tools to limit or prevent appearance of
      deleterious metabolites formed, for example, by cytochrome (cyt) P450 enzymes. In
      this paper, we evaluate the use of enzyme/DNA toxicity biosensors as tools to
      investigate enzyme inhibition. We have examined DNA damage due to cyt P450cam
      metabolism of styrene using DNA/enzyme films on pyrolytic graphite (PG)
      electrodes monitored via Ru(bpy)(3)(2+)-mediated DNA oxidation. Styrene
      metabolism initiated by hydrogen peroxide was evaluated with and without the
      inhibitors, imidazole, imidazole-4-acetic acid, and sulconazole (in micromolar
      range) to monitor DNA damage inhibition. The initial rates of DNA damage
      decreased with increased inhibitor concentrations. Linear and nonlinear fits of
      Michaelis-Menten inhibition models were used to determine apparent inhibition
      constants (K(I)*) for the inhibitors. Elucidation of the best fitting inhibition
      model was achieved by comparing correlation coefficients and the sum of the
      square of the errors (SSE) from each inhibition model. Results confirmed the
      utility of the enzyme/DNA biosensor for metabolic inhibition studies. A simple
      competitive inhibition model best approximated the data for imidazole, imidazole
      4-acetic acid and sulconazole with K(I)* of 268.2, 142.3, and 204.2 microM,
      respectively.

PMID- 19099360
TI  - Antibacterial effects of roselle calyx extracts and protocatechuic acid in ground
      beef and apple juice.
AB  - The antibacterial effects of roselle calyx aqueous and ethanol extracts and
      protocatechuic acid against food spoilage bacteria Salmonella typhimurium DT104,
      Escherichia coli O157:H7, Listeria monocytogenes, Staphylococcus aureus, and
      Bacillus cereus were examined. Minimal inhibitory concentrations of roselle calyx
      aqueous and ethanol extracts and protocatechuic acid against these bacteria were
      in the range of 112-144, 72-96, and 24-44 microg/mL, respectively. Protocatechuic
      acid content in roselle calyx aqueous and ethanol extracts was 2.8 +/- 0.7 and
      11.9 +/- 1.2 mg/g, respectively. Antibacterial activity of roselle calyx ethanol
      extract and protocatechuic acid was not affected by heat treatments from 25
      degrees to 75 degrees C and 25 degrees to 100 degrees C, respectively. After 3
      days storage at 25 degrees C, the addition of roselle calyx extracts and
      protocatechuic acid exhibited dose-dependent inhibitory effects against test
      bacteria in ground beef and apple juice, in which the roselle calyx ethanol
      extract showed greater antibacterial effects than the aqueous extract. These data
      suggest that roselle calyx ethanol extract and protocatechuic acid might be
      potent agents as food additives to prevent contamination from these bacteria.

PMID- 19099361
TI  - Click chemistry functionalized polymeric nanoparticles target corneal epithelial
      cells through RGD-cell surface receptors.
AB  - Self-assembled polymeric nanoparticles modified with targeting ligands on the
      surface provide a means for localized cell delivery. To gain greater insight into
      the possibility of derivatizing poly(2-methyl-2-carboxytrimethylene carbonate-co
      D,L-lactide) (poly(TMCC-co-LA)) nanoparticles using the Huisgen's 1,3 dipolar
      cycloaddition reaction, we synthesized amphiphilic copolymers comprising a
      hydrophobic poly(TMCC-co-LA) backbone and a hydrophilic poly(ethylene glycol)
      (PEG) pendant chain. By coupling amine-terminated PEG-azide to the carboxylic
      acid group of the poly(TMCC-co-LA) via EDC chemistry, an amphiphilic copolymer
      was formed. The poly(TMCC-co-LA)-g-PEG-N3 self-assembled in aqueous solution and
      presented azide groups on the surface of the nanoparticles. Alkyne-modified
      KGRGDS peptides were synthesized and coupled to the azide-functionalized
      nanoparticles via Huisgen's 1,3 dipolar cycloaddition, which was catalyzed by
      copper sulfate and sodium ascorbate in aqueous solution. Using coumarin-modified
      lysine (K) of the KGRGDS peptide, fluorescence was used to determine that there
      were approximately 400 peptides bound to each nanoparticle. The bioactivity of
      the GRGDS nanoparticle was confirmed with a competitive cell attachment assay
      using rabbit corneal epithelial cells. This GRGDS-nanoparticle system may be
      suitable for targeted drug delivery.

PMID- 19099362
TI  - Plant pathology: changing agricultural methods and human society.

PMID- 19099363
TI  - Johanna westerdijk: pioneer leader in plant pathology.

PMID- 19099364
TI  - Operation of graphene transistors at gigahertz frequencies.
AB  - Top-gated graphene transistors operating at high frequencies (gigahertz) have
      been fabricated and their characteristics analyzed. The measured intrinsic
      current gain shows an ideal 1/f frequency dependence, indicating a FET-like
      behavior for graphene transistors. The cutoff frequency f(T) is found to be
      proportional to the dc transconductance g(m) of the device, consistent with the
      relation f(T) = g(m)/(2piC(G)). The peak f(T) increases with a reduced gate
      length, and f(T) as high as 26 GHz is measured for a graphene transistor with a
      gate length of 150 nm. The work represents a significant step toward the
      realization of graphene-based electronics for high-frequency applications.

PMID- 19099365
TI  - Noncovalent self-assembling nucleic acid-lipid based materials.
AB  - We detail a method originally described by Okahata et al. (Macromol. Rapid
      Commun. 2002, 23, 252-255) to prepare noncovalent self-assembling films by
      exchanging the counter-ions of the nucleic acid phosphate moieties with those of
      cationic lipid amphiphiles. We are able to control the strength and surface
      properties of these films by varying the composition between blends of DNA of
      high molecular weight and RNA of low molecular weight. X-ray and AFM results
      indicate that these films have a lamellar multilayered structure with layers of
      nucleic acid separated by layers of cationic amphiphile. The tensile strength of
      the blended films between DNA and RNA increases elastically with DNA content. The
      length as well as the molecular structure of nucleic acids can affect the
      topology and mechanical properties of these films. We suspect that the
      permeability properties of these films make them good candidates for further
      biological applications in vivo.

PMID- 19099367
TI  - Perinatal echocardiography: protocols for evaluating the fetal and neonatal
      heart.
AB  - This Protocol for Evaluating the Fetal and Neonatal Heart details the
      indications, views, and measurements to be obtained for both (1) the basic
      screening examination of the fetal heart (a necessary component of all complete
      fetal anatomy evaluations) and the specialty study called (2) echocardiography as
      applied to either the fetus or neonate, using 2D and Doppler ultrasound. While
      the purpose of the screening study is to detect or exclude the possibility of a
      cardiac abnormality, echocardiography attempts to diagnose the specific anatomic
      and physiologic disruption. Also emphasized is the value of a collaborative team
      approach to management of the fetus and its parents when a cardiovascular anomaly
      is present, in an effort to achieve a smoother transition from fetus to neonate
      across the continuum of perinatal care.

PMID- 19099368
TI  - Evidence to support that spontaneous preterm labor is adaptive in nature:
      neonatal RDS is more common in "indicated" than in "spontaneous" preterm birth.
AB  - OBJECTIVES: The onset of preterm labor has been proposed to have survival value
      and to be adaptive in nature. This hypothesis would predict that induced preterm
      birth may be associated with higher rates of complications than spontaneous
      preterm birth. The purpose of this study was to determine if there is a
      difference in the frequency of neonatal respiratory distress syndrome (RDS), the
      most common neonatal complication, according to the etiology of preterm birth
      (e.g., preterm labor [PTL], preterm PROM, or pregnancies which ended because of
      maternal-fetal indications). STUDY DESIGN: The relationship between the
      occurrence of RDS and the obstetrical circumstances leading to preterm birth was
      examined in 257 consecutive singleton preterm births (gestational age: 24-32
      weeks). Cases with major congenital anomalies were excluded. The study population
      was divided into two groups according to the cause of preterm birth: 1) preterm
      birth due to PTL with intact membranes or preterm PROM (spontaneous preterm birth
      group); and 2) preterm birth due to maternal or fetal indications (indicated
      preterm birth group). RESULTS: 1) RDS was diagnosed in 47% of cases; 2) RDS was
      more common in patients with indicated preterm birth than in those with
      spontaneous preterm birth group (58.1% vs. 38.4%, P=0.002); 3) Patients with
      indicated preterm birth had a significantly higher mean gestational age at birth,
      but lower mean birth weight, lower rate of histological chorioamnionitis and
      higher rates of cesarean delivery, 5 min Apgar score of <7, and umbilical
      arterial blood pH of <7.15 than those with spontaneous preterm birth (P<0.05 for
      each); 4) Antenatal corticosteroids were used in 73.4% of cases with indicated
      preterm birth and in 76.9% of those with spontaneous preterm birth; 5)
      Multivariate analysis demonstrated that indicated preterm birth was associated
      with an increased risk of RDS after adjusting for confounding variables (OR=2.29,
      95% CI 1.22-4.29). CONCLUSIONS: 1) The rate of RDS is greater following
      "indicated" rather than spontaneous preterm birth; 2) This observation supports
      the view that spontaneous preterm labor is adaptive in nature.

PMID- 19099372
TI  - In vitro senescence of rat mesenchymal stem cells is accompanied by
      downregulation of stemness-related and DNA damage repair genes.
AB  - Mesenchymal stem cells (MSCs) are of particular interest because they are being
      tested using cell and gene therapies for a number of human diseases. MSCs
      represent a rare population in tissues. Therefore, it is essential to grow MSCs
      in vitro before putting them into therapeutic use. This is compromised by
      senescence, limiting the proliferative capacity of MSCs. We analyzed the in vitro
      senescence of rat MSCs, because this animal is a widespread model for preclinical
      cell therapy studies. After initial expansion, MSCs showed an increased growth
      doubling time, lost telomerase activity, and expressed senescence-associated beta
      galactosidase. Senescence was accompanied by downregulation of several genes
      involved in stem cell self-renewal. Of interest, several genes involved in DNA
      repair also showed a significant downregulation. Entry into senescence occurred
      with characteristic changes in Retinoblastoma (RB) expression patterns. Rb1 and
      p107 genes expression decreased during in vitro cultivation. In contrast,
      pRb2/p130 became the prominent RB protein. This suggests that RB2/P130 could be a
      marker of senescence or that it even plays a role in triggering the process in
      MSCs.

PMID- 19099366
TI  - Visfatin in human pregnancy: maternal gestational diabetes vis-a-vis neonatal
      birthweight.
AB  - OBJECTIVE: Adipose tissue dysfunction, characterized by dysregulation of
      adipokines production and/or secretion, has been implicated in the
      pathophysiology of type-2 diabetes mellitus, a metabolic complication closely
      related to gestational diabetes mellitus (GDM). Recently, an association between
      circulating maternal visfatin, a novel adipokine with metabolic and
      immunoregulatory properties, and impaired glucose metabolism as well as with
      altered fetal growth, has been proposed. The aims of this study were to determine
      whether there is an association between maternal plasma visfatin concentration,
      GDM, and a large-for-gestational-age (LGA) newborn. STUDY DESIGN: This cross
      sectional study, included pregnant women at term in the following groups: 1)
      normal pregnancy and an appropriate-for-gestational-age (AGA) neonate (n=54); 2)
      normal pregnancy and an LGA newborn (n=47); 3) GDM and an AGA newborn (n=56); 4)
      GDM and an LGA newborn (n=45). The study population was further stratified by
      first trimester BMI (<25 vs. > or =25 kg/m(2)). Maternal plasma visfatin
      concentration was determined by ELISA. Parametric and non-parametric statistics
      were used for analysis. RESULTS: 1) Among women who delivered an AGA neonate, the
      median maternal plasma concentration of visfatin was higher in patients with GDM
      than in those with a normal pregnancy; 2) Among women with a normal pregnancy,
      those who delivered an LGA neonate had a higher median maternal plasma visfatin
      concentration than those who delivered an AGA neonate; 3) among patients with
      normal BMI, there were no significant differences in the median maternal plasma
      visfatin concentration between the four study groups; and 4) maternal GDM, as
      well as delivery of an LGA neonate were independently associated with a higher
      maternal plasma visfatin concentrations. CONCLUSION: The linkage between
      increased maternal circulating visfatin and the presence of GDM or delivery of an
      LGA neonate supports the hypothesis that perturbation of adipokines homeostasis
      may play a role in the pathophysiology of GDM or excess fetal growth.

PMID- 19099374
TI  - Pulmonary passage is a major obstacle for intravenous stem cell delivery: the
      pulmonary first-pass effect.
AB  - Intravenous (IV) stem cell delivery for regenerative tissue therapy has been
      increasingly used in both experimental and clinical trials. However, recent data
      suggest that the majority of administered stem cells are initially trapped in the
      lungs. We sought to investigate variables that may affect this pulmonary first
      pass effect. In anesthetized Sprague-Dawley rats, silicone tubing catheters were
      placed in the left internal jugular vein and common carotid artery. We
      investigated four different cell types: mesenchymal stromal cells (MSC),
      multipotent adult progenitor cells (MAPCs), bone marrow-derived mononuclear cells
      (BMMC), and neural stem cells (NSC). Cells were co-labeled with Qtracker 655 (for
      flow cytometry) and Qtracker 800 (for infrared imaging) and infused intravenously
      with continual arterial sample collection. Samples were analyzed via flow
      cytometry to detect labeled cells reaching the arterial circulation. Following
      sampling and exsanguination, heart, lungs, spleen, kidney, and liver were
      harvested and placed on an infrared imaging system to identify the presence of
      labeled cells. The majority of MSCs were trapped inside the lungs following
      intravenous infusion. NSC and MAPC pulmonary passage was 2-fold and BMMC passage
      was 30-fold increased as compared to MSCs. Inhibition of MSC CD49d significantly
      increased MSC pulmonary passage. Infusion via two boluses increased pulmonary MSC
      passage as compared to single bolus administration. Infrared imaging revealed
      stem cells evenly distributed over all lung fields. Larger stem and progenitor
      cells are initially trapped inside the lungs following intravenous administration
      with a therapeutically questionable number of cells reaching the arterial system
      acutely.

PMID- 19099373
TI  - Isolation and characterization of neural crest stem cells derived from in vitro
      differentiated human embryonic stem cells.
AB  - The neural crest is a transient structure of vertebrate embryos that initially
      generates neural crest stem cells (NCSCs) which then migrate throughout the body
      to produce a diverse array of mature tissue types. Due to the rarity of adult
      NCSCs as well as ethical and technical issues surrounding isolation of early
      embryonic tissues, biologic studies of human NCSCs are extremely challenging.
      Thus, much of what is known about human neural crest development has been
      inferred from model organisms. In this study, we report that functional NCSCs can
      be rapidly generated and isolated from in vitro-differentiated human embryonic
      stem cells (hESCs). Using the stromal-derived inducing activity (SDIA) of PA6
      fibroblast co-culture we have induced hESCs to differentiate into neural crest.
      Within 1 week, migrating cells that express the early neural crest markers p75
      and HNK1 as well as numerous other genes associated with neural crest induction
      such as SNAIL, SLUG, and SOX10 are detectable. Fluorescence-activated cell
      sorting (FACS)-based isolation of the p75-positive population enriches for cells
      with genetic, phenotypic, and functional characteristics of NCSCs. These p75
      enriched cells readily form neurospheres in suspension culture, self-renew to
      form secondary spheres, and give rise under differentiation conditions to
      multiple neural crest lineages including peripheral nerves, glial, and
      myofibroblastic cells. Importantly, these cells differentiate into neural crest
      derivatives when transplanted into developing chick embryos in vivo. Thus, this
      SDIA protocol can be used to successfully and efficiently isolate early human
      NCSCs from hESCs in vitro. This renewable source of NCSCs provides an invaluable
      source of cells for studies of both normal and disordered human neural crest
      development.

PMID- 19099375
TI  - A new approach to investigating embryonic stem cell differentiation.

PMID- 19099376
TI  - Accuracy of percutaneous placement of a ventriculoatrial shunt under
      ultrasonography guidance: a retrospective study at a single institution.
AB  - The authors report their experience using preoperative chest radiography and
      intraoperative ultrasonography for percutaneous positioning of the distal end of
      the catheter when placing ventriculoatrial (VA) shunts in patients with
      hydrocephalus. The distal portion of VA shunt catheters were percutaneously
      placed into the internal jugular vein with the aid of intraoperative
      ultrasonography in 14 consecutive adults. In all cases, the technique was easy,
      there were no postoperative complications, and postoperative chest radiography
      demonstrated good positioning of the distal catheter tip. One patient presented
      with a shunt infection and needed a shunt replacement. The authors therefore
      conclude that percutaneous placement of a VA shunt under preoperative
      radiographic guidance and ultrasonographic monitoring is a safe, effective, and
      reliable technique that is simple to learn.

PMID- 19099377
TI  - Embolization of the middle meningeal artery for the treatment of epidural
      hematoma.
AB  - Epidural hematomas (EDHs) are sometimes treated nonoperatively. Decision making,
      however, is not always perfect, and some hematomas chosen for observation later
      deteriorate and require surgical clot removal. With the current endovascular
      technology it is possible to embolize meningeal arteries to stop epidural
      bleeding. In this study, the author presents his experience in the treatment of a
      patient with a troublesome postoperative EDH successfully controlled with
      embolization therapy. This treatment is also useful in posttraumatic EDH and may
      obviate the need for surgery in some patients with EDHs who present early after
      injury and without significant mass effect.

PMID- 19099378
TI  - Safe entry point for twist-drill craniostomy of a chronic subdural hematoma.
AB  - OBJECT: Twist-drill craniostomy (TDC) with closed-system drainage is an effective
      treatment option for chronic subdural hematoma (CSDH). Because the entry point
      for TDC has not been described in a definitive area, the aim of this study was to
      define the optimal twist-drill entry point for CSDH. METHODS: The authors
      selected 40 random cases involving selective catheter angiography of the external
      carotid artery, regardless of study purpose, to evaluate the course of the middle
      meningeal artery. Furthermore, 50 skull radiographs were reviewed to assess the
      relation of the vascular groove to the coronal suture. On the basis of the
      radiological anatomical study, the authors propose that the normal TDC entry
      point should be 1 cm anterior to the coronal suture at the level of the superior
      temporal line (STL). Thirty patients with symptomatic CSDH were treated using TDC
      with closed-system drainage at the proposed entry point. The thicknesses of the
      hematoma and the skull were measured at the proposed entry point. The congruence
      between the proposed entry point and postoperative craniostomy was estimated and
      complications were evaluated. RESULTS: In the radiological study, all the
      branches of the middle meningeal artery ran posterior to the coronal suture and
      the vascular grooves were also located posterior to the coronal suture at the
      level of the STL. The average distance of the vascular grooves was 8.0 +/-5.8 mm.
      Thirty-five procedures were performed. The coronal suture and the STL could be
      identified clearly on brain CT scans. The mean thickness of the skull and the
      CSDH at the proposed point was 8 mm (range 5-13 mm) and 20 mm (range 10-28 mm),
      respectively. All the TDCs except 1 were congruent with the preoperative brain CT
      scans. One CSDH recurred 1 month after the first operation and was revised using
      the same procedure. No other complications occurred. CONCLUSIONS: One centimeter
      anterior to the coronal suture at the level of the STL is suitable as the normal
      entry point of the TDC for symptomatic CSDH. The thickness of the CSDH can be
      measured at this point on a preoperative brain CT scan. Furthermore, the entry
      point on the scalp can be accurately estimated using surface landmarks.

PMID- 19099379
TI  - Insular gliomas: the case for surgical management.
AB  - OBJECT: Treatment for insular (paralimbic) gliomas is controversial. In this
      report the authors summarize their experience with microsurgical resection of
      insular tumors. METHODS: The authors analyzed complications, functional outcomes,
      and survival in a series of 101 operations performed in 94 patients between 1995
      and 2005. RESULTS: A > 90% resection was achieved in 42%, and 70-90% tumor
      removal was accomplished in 51% of cases. Functional outcomes varied considerably
      between patient subgroups. For example, in neurologically intact patients < or =
      40 years of age with WHO Grade I-III tumors, good outcomes (Karnofsky Performance
      Scale Score 80-100) were seen in 91% of cases. Predictors of an unfavorable
      functional outcome included histological features of glioblastoma, advanced age,
      and a low preoperative Karnofsky Performance Scale score. One year after surgery,
      76% of patients who had presented with epilepsy were seizure free or experienced
      only isolated, nondebilitating seizures. Surprisingly good survival rates were
      seen after surgery for anaplastic gliomas. The median survival for patients with
      anaplastic astrocytomas (WHO Grade III) was 5 years, and the 5-year survival rate
      for those with anaplastic oligodendroglial tumors was 80%. Independent predictors
      of survival included younger age, favorable histological features (WHO Grade I
      and oligodendroglial tumors), Yasargil Type 5A/B tumors with frontal extensions,
      and more extensive resections. CONCLUSIONS: Insular tumor surgery carries
      substantial complication rates. However, surprisingly similar figures have been
      reported in large unselected craniotomy series and also after alternative
      treatment regimens. In view of the oncological benefits of resective surgery, our
      data would therefore argue for microsurgery as the primary treatment for most
      patients with a presumed WHO Grade I-III tumor. Patients with glioblastomas
      and/or age > 60 years require a more cautious approach.

PMID- 19099380
TI  - The neurophysiology and effect of deep brain stimulation in a patient with 1
      methyl-4-phenyl-1,2,3,6-tetrahydropyridine-induced parkinsonism.
AB  - Parkinsonism caused by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)
      exposure was first identified in intravenous drug users. This neurotoxicant has
      since been used extensively in nonhuman primates to induce an experimental model
      of Parkinson disease (PD). In this study, the authors examined the intraoperative
      physiological characteristics and efficacy of subthalamic nucleus deep brain
      stimulation (DBS) in 1 of only 4 known living patients with MPTP-induced
      parkinsonism. The physiological recordings were consistent with recordings from
      MPTP-treated primates and humans with PD, thus providing further validation for
      the MPTP model in the study of the neurophysiology of the nigrostriatal
      dopaminergic deficit in PD. Furthermore, DBS produced a significant clinical
      improvement in this patient similar to the improvement seen after DBS in patients
      with idiopathic PD. This unique case has important implications for translational
      research that employs the MPTP-primate model for symptomatic therapy in PD.

PMID- 19099381
TI  - Conservative management of 386 cases of unilateral vestibular schwannoma: tumor
      growth and consequences for treatment.
AB  - OBJECT: The object of this study was to evaluate the natural history, pattern,
      and occurrence of tumor growth and its consequences for treatment of small-sized
      vestibular schwannomas (VSs). METHODS: From 1990 to 2005, 386 patients underwent
      conservative management for VS because of the following: age > 60 years, poor
      health/medical risks, risk of deterioration of good hearing, small tumor size,
      minimal or no incapacitating symptoms, and/or patient preference. Tumor size was
      measured by MR imaging according to the guidelines of the Committee on Hearing
      and Equilibrium. The first MR imaging study was performed 1 year after diagnosis,
      and subsequent imaging was performed yearly or every 2 years depending on the
      appearance of new symptoms, tumor growth, or both. RESULTS: Sixty-one patients
      were lost to follow-up the first year after presentation. Of the 325 patients for
      whom 1-year follow-up data were available, 39 showed tumor growth > or = 3 mm.
      Conservative management was discontinued for these 39 patients. The patients who
      returned for follow-up were evaluated at 1- or 2-year intervals depending on
      tumor growth. The authors extrapolated to obtain data for 2-year intervals,
      yielding data for 160, 56, 21, and 8 patients at 3, 5, 7, and 9 years after
      initial presentation, respectively. The overall mean tumor growth rate (+/
      standard deviation) was 1.15 +/- 2.4 mm/year. This rate was estimated by pooling
      all values of tumor growth that had been determined for all patients and dividing
      by the total number of "events," with each assessment constituting an event. In
      58.6% of patients, the annual tumor growth rate was < 1 mm/year; in 29.2%, 1-3
      mm/year; and in 12.2%, > or = 3 mm/ year. The growth rates of intrameatal (1.02
      +/- 1.8 mm/year) and extrameatal (1.40 +/- 3.1 mm/year) tumors did not differ
      significantly. No significant association was found between tumor growth rate and
      sex, age, initial hearing status, or initial tumor grade. Delay in diagnosis was
      the only significant factor associated with tumor growth rate. During follow-up,
      conservative management was discontinued for 77 (23.7%) of the 325 patients for
      whom at least 12-month follow-up data were available; surgery was performed in 60
      (77.9%) and radiation therapy in 17 (22.1%). CONCLUSIONS: The results of this
      study support the role of a conservative "wait-and-scan" policy of management for
      small-sized VSs because most have a slow growth rate. Long-term neuroimaging
      follow-up is needed even with non-growing tumors.

PMID- 19099382
TI  - Politeness, policies, and politics.

PMID- 19099383
TI  - Sialolithiasis of the submandibular salivary gland treated with the 810- to 830
      nm diode laser.
AB  - OBJECTIVE: Surgical management of salivary gland diseases has always been
      challenging because it carries a considerable risk of nerve damage. This study
      evaluates an innovative ambulatory laser-aided technique that may be an
      alternative to traditional treatment, and presents our 5-y experience of salivary
      gland excision. MATERIALS AND METHODS: Twenty-five submandibular salivary gland
      excisions were performed with an 810- to 830-nm diode laser. The diagnosis was
      sialolithiasis with stones in the salivary gland duct above the glandular hilum.
      A 320-microm flexible delivery fiber was used in continuous wave mode at 2.5 W
      power. The procedure consisted of locating the stone, isolating the duct from the
      surrounding tissues, introducing a button probe, ductal incision above the stone,
      sialolithotomy, and checking duct patency. RESULTS: The overall success rate was
      92%. The largest stone removed was 4.5 cm in size. In 1 patient (4%), an
      additional undetected stone was diagnosed by endoscopy after removal of the stone
      from the duct, and in 1 patient (4%), synechiae formed in the duct during healing
      and duct patency had to be restored with a probe. We had no cases of transient
      palsy or paresis of the mandibular branch of the facial or lingual nerves.
      CONCLUSION: Use of the 810-nm laser is safe for this type of surgical procedure,
      carries a low complication rate, and is a valid alternative to traditional
      surgery. It is indicated as the procedure of choice in cases of stones located in
      the duct above the kink leading into the mylohyoid muscle, and above the
      glandular hilum.

PMID- 19099384
TI  - Ablation rate and morphology of superficial and deep dentin irradiated with
      different Er:YAG laser energy levels.
AB  - OBJECTIVE: In this study we evaluated the ablation rate of superficial and deep
      dentin irradiated with different Er:YAG laser energy levels, and observed the
      micromorphological aspects of the lased substrates with a scanning electron
      microscope (SEM). BACKGROUND DATA: Little is known about the effect of Er:YAG
      laser irradiation on different dentin depths. MATERIALS AND METHODS: Sixty molar
      crowns were bisected, providing 120 specimens, which were randomly assigned into
      two groups (superficial or deep dentin), and later into five subgroups (160, 200,
      260, 300, or 360 mJ). Initial masses of the specimens were obtained. After laser
      irradiation, the final masses were obtained and mass losses were calculated
      followed by the preparation of specimens for SEM examination. Mass-loss values
      were subjected to two-way ANOVA and Fisher's least significant difference
      multiple-comparison tests (p > 0.05). RESULTS: There was no difference between
      superficial and deep dentin. A significant and gradual increase in the mass-loss
      values was reached when energies were raised, regardless of the dentin depth. The
      energy level of 360 mJ showed the highest values and was statistically
      significantly different from the other energy levels. The SEM images showed that
      deep dentin was more selectively ablated, especially intertubular dentin,
      promoting tubule protrusion. At 360 mJ the micromorphological features were
      similar for both dentin depths. CONCLUSION: The ablation rate did not depend on
      the depth of the dentin, and an energy level lower than 360 mJ is recommended to
      ablate both superficial and deep dentin effectively without causing tissue
      damage.

PMID- 19099385
TI  - Knoop microhardness and FT-Raman spectroscopic evaluation of a resin-based dental
      material light-cured by an argon ion laser and halogen lamp: an in vitro study.
AB  - OBJECTIVE: The purpose of this study was to evaluate in vitro the Knoop
      microhardness (Knoop hardness number [KHN]) and the degree of conversion using FT
      Raman spectroscopy of a light-cured microhybrid resin composite (Z350-3M-ESPE)
      Vita shade A3 photopolymerized with a halogen lamp or an argon ion laser.
      BACKGROUND DATA: Optimal polymerization of resin-based dental materials is
      important for longevity of restorations in dentistry. MATERIALS AND METHODS:
      Thirty specimens were prepared and inserted into a disc-shaped
      polytetrafluoroethylene mold that was 2.0 mm thick and 3 mm in diameter. The
      specimens were divided into three groups (n = 10 each). Group 1 (G1) was light
      cured for 20 sec with an Optilux 501 halogen light with an intensity of 1000
      mW/cm(2). Group 2 (G2) was photopolymerized with an argon laser with a power of
      150 mW for 10 sec, and group 3 (G3) was photopolymerized with an argon laser at
      200 mW of power for 10 sec. All specimens were stored in distilled water for 24 h
      at 37 degrees C and kept in lightproof containers. For the KHN test five
      indentations were made and a depth of 100 microm was maintained in each specimen.
      One hundred and fifty readings were obtained using a 25-g load for 45 sec. The
      degree of conversion values were measured by Raman spectroscopy. KHN and degree
      of conversion values were obtained on opposite sides of the irradiated surface.
      KHN and degree of conversion data were analyzed by one-way ANOVA and Tukey tests
      with statistical significance set at p < 0.05. RESULTS: The results of KHN
      testing were G1 = 37.428 +/- 4.765; G2 = 23.588 +/- 6.269; and G3 = 21.652 +/-
      4.393. The calculated degrees of conversion (DC%) were G1 = 48.57 +/- 2.11; G2 =
      43.71 +/- 3 .93; and G3 = 44.19 +/- 2.71. CONCLUSIONS: Polymerization with the
      halogen lamp (G1) attained higher microhardness values than polymerization with
      the argon laser at power levels of 150 and 200 mW; there was no difference in
      hardness between the two argon laser groups. The results showed no statistically
      significant different degrees of conversion for the polymerization of composite
      samples with the two light sources tested.

PMID- 19099386
TI  - Effect of Er:YAG and CO2 lasers with and without sodium fluoride gel on dentinal
      tubules: a scanning electron microscope examination.
AB  - OBJECTIVE: The aim of this pilot study was to evaluate the occluding effect of
      erbium:yttrium-aluminum-garnet (Er:YAG) and carbon dioxide (CO2) lasers as
      monotherapy and in combination with topical fluoride gel on human dentinal
      tubules by scanning electron microscopic (SEM) examination. MATERIALS AND
      METHODS: Thirty-six dentine specimens with exposed dentinal tubule orifices were
      included in this study. The samples were divided into six groups. Group A served
      as controls, group B was treated with 2% sodium fluoride (NaF) gel alone, groups
      C and D were irradiated with Er:YAG (30 Hz, 60 mJ, for 10 sec) and CO2 (1 W,
      continuous-wave mode, for 10 sec) lasers, respectively, and groups E and F
      received NaF gel plus Er:YAG and CO2 laser irradiation, respectively. RESULTS:
      Under SEM analysis, numerous exposed, normally-structured dentinal tubule
      orifices were seen in the control group. Some narrowing of the exposed tubule
      orifices was seen in group B. A melted, irregular surface structure with small
      peaks was observed in group C. The surface of group D also had a melted
      appearance, but a fibrillar deformation of the surface structure was seen on the
      specimens. However, the surface morphologies seen were remarkably different in
      groups E and F. While the tubule orifices were obviously occluded but depressed
      into craters in group E, the surface structure of group F primarily showed a
      smooth appearance. In terms of numbers and diameters of open dentinal tubules,
      there was no significant difference between the laser-alone and combination
      groups, whereas the difference was found to be significant when the control and
      NaF groups were compared with each other and the remaining laser-alone or
      combination groups. CONCLUSION: The dentinal tubules in all laser groups were
      occluded after laser irradiation, but more marked occlusions were observed when
      laser and NaF gel were combined.

PMID- 19099387
TI  - Microleakage of class V cavities with different adhesive systems prepared by a
      diamond instrument and different parameters of Er:YAG laser irradiation.
AB  - OBJECTIVE: The aim of this study was to evaluate the microleakage of composite
      resin restorations using two different dentine adhesive systems prepared with a
      diamond instrument and different parameters of Er:YAG laser irradiation.
      BACKGROUND DATA: Information on this topic with regard to preparing class V
      cavities with different parameters of Er:YAG laser irradiation and adhesive
      systems is scarce. MATERIALS AND METHODS: Two hundred class V cavities were
      assigned to ten groups (n = 20 each): group 1: Er:YAG laser (5 Hz, 600 mJ) +
      phosphoric acid (PA) + Adper Single Bond 2 (ASB2); group 2: Er:YAG laser (10 Hz,
      300 mJ) + PA + ASB2; group 3: Er:YAG laser (15 Hz, 200 mJ) + PA + ASB2; group 4:
      Er:YAG laser (20 Hz, 150 mJ) + PA + ASB2; group 5: diamond instrument + PA +
      ASB2; group 6: Er:YAG laser (5 Hz, 600 mJ) + Adper Prompt L-Pop (APLP); group 7:
      Er:YAG laser (10 Hz, 300 mJ) + APLP; group 8: Er:YAG laser (15 Hz, 200 mJ) +
      APLP; group 9: Er:YAG laser (20 Hz, 150 mJ) + APLP; and group 10: diamond
      instrument + APLP. Cavities were restored with a nanofill composite (Filtek
      Supreme XT Body). After thermocycling, the specimens were stained with 0.5%
      aqueous basic fuchsin dye and sectioned bucco-lingually. Dye penetration was then
      scored. The data were analyzed using the Kruskal-Wallis and Mann-Whitney U tests
      with Bonferroni correction. The Wilcoxon signed ranks test was used to compare
      occlusal and gingival scores. RESULTS: Leakage was seen in all groups at both the
      occlusal and gingival margins. The Kruskal-Wallis test showed statistically
      significant differences among the 10 groups (p < 0.001). The gingival margins had
      more microleakage than the occlusal margins (p < 0.001). Pairwise analysis by the
      Mann-Whitney U test showed that statistically significant differences (p < 0.05)
      in microleakage were found between groups 3 and 5 (3 > 5), 5 and 7 (7 > 5), and 7
      and 8 (7 > 8) at the gingival margin, and between groups 3 and 6 (6 > 3), 3 and 7
      (7 > 3), 4 and 6 (6 > 4), and 4 and 7 (7 > 4) at the occlusal margin. CONCLUSION:
      We concluded that for all groups, microleakage values were higher at the gingival
      margins. The use of the Er:YAG laser for cavity preparation with different
      parameters and different dentine adhesive systems influenced the marginal sealing
      of composite resin restorations.

PMID- 19099388
TI  - Absorption measurements of cell monolayers relevant to mechanisms of laser
      phototherapy: reduction or oxidation of cytochrome c oxidase under laser
      radiation at 632.8 nm.
AB  - OBJECTIVE: The objective of this work was a further investigation of redox
      mechanisms of laser phototherapy on the cellular level. BACKGROUND DATA:
      Cytochrome c oxidase, the terminal enzyme of the mitochondrial respiratory chain,
      is believed to work as the photoacceptor to modulate cellular metabolism in laser
      phototherapy. MATERIALS AND METHODS: The changes in the absorption spectra of
      HeLa-cell monolayers before and after irradiation at 632.8 nm using fast multi
      channel recording were evaluated by the intensity ratio between the peaks at 770
      and 670 nm (intensity ratio criterion). RESULTS: By the intensity ratio
      criterion, the irradiation effects (reduction or oxidation of the photoacceptor)
      depended on the initial redox status of cytochrome c oxidase. The irradiation
      (three times at 632.8 nm, dose = 6.3 x 103 J/m(2), tau(irrad.) = 10 sec,
      tau(record.) = 600 msec) of cells initially characterized by relatively oxidized
      cytochrome c oxidase caused first a reduction of the photoacceptor, and then its
      oxidation (a bell-shaped curve). The irradiation by the same scheme of the cells
      with initially relatively reduced cytochrome c oxidase caused first oxidation and
      then a slight reduction of the enzyme (a curve opposite to the bell-shaped
      curve). CONCLUSION: The experimental results of our work demonstrate that
      irradiation at 632.8 nm causes either a (transient) relative reduction of the
      photoacceptor, putatively cytochrome c oxidase, or its (transient) relative
      oxidation, depending on the initial redox status of the photoacceptor. The
      maximum in the bell-shaped dose-dependence curve or the minimum of the reverse
      curve is the turning point between the prevailing of oxidation or reduction
      processes. Our results are evidence that the bell-shaped dose dependences
      recorded for various cellular responses are characteristic also for redox changes
      in the photoacceptor, cytochrome c oxidase.

PMID- 19099389
TI  - Bilateral macular holes immediately following Nd:YAG laser peripheral iridotomy.

PMID- 19099392
TI  - Photomedicine and LLLT literature watch.

PMID- 19099393
TI  - A comparison of two determination methods for studying degradation kinetics of
      the major anthocyanins from blood orange.
AB  - The thermal degradation of cyanidin 3-(6''-malonyl) glucoside and cyanidin 3
      glucoside, which are the two major anthocyanins in blood orange juice, have been
      investigated using the pH-differential method and RP-HPLC method, respectively.
      Similar results could be obtained when the degradation kinetics of cyanidin 3
      glucoside were studied by either the HPLC method or the pH-differential method.
      However, contrary results were obtained in the case of cyanidin 3-(6''-malonyl)
      glucoside. The HPLC analysis indicated that cyanidin 3-(6''-malonyl) glucoside
      was labile to eliminate a malonyl moiety to form cyanidin 3-glucoside before
      disappearing during thermal treatment and showed a lower thermal stability than
      cyanidin 3-glucoside, whereas the result obtained by the pH-differential method
      actually reflected the content of both cyanidin 3-(6''-malonyl) glucoside and its
      degradation intermediate. This caused an overestimate of the stability of
      cyanidin 3-(6''-malonyl) glucoside.

PMID- 19099394
TI  - The capital to drive scientific research.

PMID- 19099395
TI  - Peptide inhibitors of HIV-1 egress.
AB  - HIV-1 release requires a direct interaction between the p6 domain of the Gag
      protein and Tsg101, a component of the cellular endosomal sorting complex
      required for transport I (ESCRT-I). Disruption of the binding between Gag and
      Tsg101 is highly detrimental to particle release, making this viral-host cell
      interaction a potential target for the development of novel anti-HIV-1 agents. An
      article in this issue reports on the application of a bacterial reverse two
      hybrid strategy to identify a cyclic peptide that disrupts Gag-Tsg101 binding and
      suppresses HIV-1 particle release.

PMID- 19099396
TI  - Analysis of protein complex hierarchy in living cells.

PMID- 19099397
TI  - A novel histone acetyltransferase inhibitor modulating Gcn5 network:
      cyclopentylidene-[4-(4'-chlorophenyl)thiazol-2-yl)hydrazone.
AB  - Acetylation is a key modulator of genome accessibility through decondensation of
      the chromatin structure. The balance between acetylation and opposite
      deacetylation is, in fact, a prerequisite for several cell functions and
      differentiation. To find modulators of the histone acetyltransferase Gcn5p, we
      performed a phenotypic screening on a set of newly synthesized molecules derived
      from thiazole in budding yeast Saccharomyces cerevisiae. We selected compounds
      that induce growth inhibition in yeast strains deleted in genes encoding known
      histone acetyltransferases. A novel molecule CPTH2, cyclopentylidene-[4-(4'
      chlorophenyl)thiazol-2-yl)hydrazone, was selected based on its inhibitory effect
      on the growth of a gcn5Delta strain. We demonstrated a specific chemical-genetic
      interaction between CPTH2 and HAT Gcn5p, indicating that CPTH2 inhibits the Gcn5p
      dependent functional network. CPTH2 inhibited an in vitro HAT reaction, which is
      reverted by increasing concentration of histone H3. In vivo, it decreased
      acetylation of bulk histone H3 at the specific H3-AcK14 site. On the whole, our
      results demonstrate that CPTH2 is a novel HAT inhibitor modulating Gcn5p network
      in vitro and in vivo.

PMID- 19099398
TI  - Synthesis, reduction potentials, and antitubercular activity of ring A/B
      analogues of the bioreductive drug (6S)-2-nitro-6-{[4
      (trifluoromethoxy)benzyl]oxy}-6,7-dihydro-5H-imidazo[2,1-b][1,3]oxazine (PA-824).
AB  - The nitroimidazooxazine S-1 (PA-824) is a new class of bioreductive drug for
      tuberculosis. A series of related bicyclic nitroheterocycles was synthesized,
      designed to have a wide range of one-electron reduction potentials E(1) (from 
      570 to -338 mV, compared with -534 mV for S-1). The observed E(1) values closely
      correlated with the sigma(m) values of the heteroatom at the 4/8-position of the
      adjacent six-membered ring. Although the compounds spanned a range of E(1) values
      around that of S-1, only the nitroimidazothiazines showed significant
      antitubercular activity (at a similar level of potency), suggesting that E(1) is
      not the main driver of efficacy. Furthermore, there was a correlation between
      activity and the formation of imidazole ring-reduced products at the two-electron
      level, pointing to the potential importance of this reduction pathway, which is
      determined by the nature of the substituent at the 2-position of the 4
      nitroimidazole ring.

PMID- 19099399
TI  - Virtual screening and prediction of site of metabolism for cytochrome P450 1A2
      ligands.
AB  - With the availability of an increasing number of high resolution 3D structures of
      human cytochrome P450 enzymes, structure-based modeling tools are more readily
      used. In this study we explore the possibilities of using docking and scoring
      experiments on cytochrome P450 1A2. Three different questions have been
      addressed: 1. Binding orientations and conformations were successfully predicted
      for various substrates. 2. A virtual screen was performed with satisfying
      enrichment rates. 3. A classification of individual compounds into active and
      inactive was performed. It was found that while docking can be used successfully
      to address the first two questions, it seems to be more difficult to perform the
      classification. Different scoring functions were included, and the well
      characterized water molecule in the active site was included in various ways.
      Results are compared to experimental data and earlier classification data using
      machine learning methods. The possibilities and limitations of using structure
      based drug design tools for cytochrome P450 1A2 come to light and are discussed.

PMID- 19099401
TI  - Chemistry and bioactivity of olive biophenols in some antioxidant and
      antiproliferative in vitro bioassays.
AB  - The major biophenols in olives and the crude extract and ethyl acetate fraction
      from olive mill waste were studied for their ability to counteract different
      stages of oxidative damage, that is, hydrogen peroxide, superoxide radical (SOR),
      and hydroxyl radical in vitro. Antiproliferative activity on colon cancer (HT-29)
      and gastric cancer (AGS) cell lines was measured by 3-(4,5-dimethylthiazol-2-yl)
      2,5-diphenyltetrazolium bromide bioassay. Emphasis was given to how the observed
      in vitro activity is controlled by the structural feature of biophenols and
      possible synergism and antagonism. While in some bioassays, for example, 2,2'
      diphenyl-1-picrylhydrazyl, the nonphenolic moiety had minimal affect, it had a
      significant role in the SOR scavenging bioassay. Verbascoside was more active
      than caffeic acid or hydroxytyrosol evaluated individually or in equimolar
      mixtures in some bioassays. Mixtures of biophenols were more active than
      individual biophenols as antiproliferative agents. Overall, the mixture of
      hydroxytyrosol/caffeic acid and the biophenol extracts were more effective in
      protecting DNA from oxidative damage and inhibiting the growth of cancer cells.

PMID- 19099400
TI  - Urine metabolites reflect time-dependent effects of cyclosporine and sirolimus on
      rat kidney function.
AB  - The clinical use of the immunosuppressant calcineurin inhibitor cyclosporine is
      limited by its nephrotoxicity. This is enhanced when combined with the
      immunosuppressive mTOR inhibitor sirolimus. Nephrotoxicity of both drugs is not
      yet fully understood. The goal was to gain more detailed mechanistic insights
      into the time-dependent effects of cyclosporine and sirolimus on the rat kidney
      by using a comprehensive approach including metabolic profiling in urine ((1)H
      NMR spectroscopy), kidney histology, kidney function parameters in plasma,
      measurement of glomerular filtration rates, the oxidative stress marker 15-F(2t)
      isoprostane in urine, and immunosuppressant concentrations in blood and kidney.
      Male Wistar rats were treated with vehicle (controls), cyclosporine (10/25
      mg/kg/day), and/or sirolimus (1 mg/kg/day) by oral gavage once daily for 6 and 28
      days. Twenty-eight day treatment led to a decrease of glomerular filtration rates
      (cyclosporine, -59%; sirolimus, -25%). These were further decreased when both
      drugs were combined (-86%). Histology revealed tubular damage after treatment
      with cyclosporine, which was enhanced when sirolimus was added. No other part of
      the kidney was affected. (1)H NMR spectroscopy analysis of urine (day 6) revealed
      time-dependent changes of 2-oxoglutarate, citrate, and succinate concentrations.
      In combination with increased urine isoprostane concentrations, these changes
      indicated oxidative stress. After 28 days of cyclosporine treatment, urine
      metabonomics shifted to patterns typical for proximal tubular damage with
      reduction of Krebs cycle intermediates and trimethylamine-N-oxide concentrations,
      whereas acetate, lactate, trimethylamine, and glucose concentrations increased.
      Again, sirolimus enhanced these negative effects. Our results indicate that
      cyclosporine and/or sirolimus induce damage of the renal tubular system. This is
      reflected by urine metabolite patterns, which seem to be more sensitive than
      currently used clinical kidney function markers such as creatinine concentrations
      in serum. Metabolic profiling in urine may provide the basis for the development
      of toxicodynamic monitoring strategies for immunosuppressant nephrotoxicity.

PMID- 19099402
TI  - Influence of cell surface appendages on the bacterium-substratum interface
      measured real-time using QCM-D.
AB  - Quartz crystal microbalance with dissipation (QCM-D) utilizes an oscillating
      quartz crystal to register adsorption of rigid masses through a decrease in its
      resonance frequency f. In addition, QCM-D has the ability to measure the
      dissipative nature of nonrigid masses adhering to the crystal surface in the form
      of oscillation amplitude decay time. Although QCM has been applied to register
      bacterial adhesion to the crystal surface, full interpretation of the frequency
      change and dissipation signal has hitherto been impossible due to the complex
      interactions within the distance of 250 nm between the substratum and the
      bacterial cell surface. Here, we study adhesion of a series of Streptococcus
      salivarius mutants, possessing various surface appendages of known lengths, as a
      function of time using QCM-D. In addition, the number of bacteria adhering to the
      crystal surface was determined. The results show that adhesion of a "bald"
      bacterium, completely devoid of surface appendages, is registered as a frequency
      decrease. Adhesion of bacteria possessing surface appendages yields either a much
      smaller decrease or an increase in frequency, despite the fact they adhere in
      higher numbers. Furthermore, the magnitude of frequency and dissipation shifts
      was found to be influenced by the distance at which the cell body was held from
      the sensor surface by its surface appendages.

PMID- 19099403
TI  - Protein engineering of redox-active enzymes.
AB  - Redox-active enzymes perform many key biological reactions. The electron transfer
      process is complex, not only because of its versatility, but also because of the
      intricate and delicate modulation exerted by the protein scaffold on the redox
      properties of the catalytic sites. Nowadays, there is a wealth of information
      available about the catalytic mechanisms of redox-active enzymes and the time is
      propitious for the development of projects based on the protein engineering of
      redox-active enzymes. In this review, we aim to provide an updated account of the
      available methods used for protein engineering, including both genetic and
      chemical tools, which are usually reviewed separately. Specific applications to
      redox-active enzymes are mentioned within each technology, with emphasis on those
      cases where the generation of novel functionality was pursued. Finally, we focus
      on two emerging fields in the protein engineering of redox-active enzymes: the
      construction of novel nucleic acid-based catalysts and the remodeling of intra
      molecular electron transfer networks. We consider that the future development of
      these areas will represent fine examples of the concurrence of chemical and
      genetic tools.

PMID- 19099407
TI  - Innovative analytical methodology combining micro-x-ray diffraction, scanning
      electron microscopy-based mineral maps, and diffuse reflectance infrared fourier
      transform spectroscopy to characterize archeological artifacts.
AB  - Excavations at the 14th century Moorish rampart (Granada, Spain) unearthed a
      brick oven alongside black ash and bone stratigraphic layers. In situ evidence
      suggests the oven served to fabricate a wall coating including powdered burnt
      bones. Original ad hoc analyses improved on conventional methods were used to
      confirm this hypothesis. These methods enable (i) nondestructive micro-X-ray
      diffraction (mu-XRD) for fast mineralogical data acquisition (approximately 10 s)
      and moderately high spatial (approximately 500 microm) resolution and (ii)
      identification and imaging of crystalline components in sample cross-sections via
      mineral maps, yielding outstanding visualization of grain distribution and
      morphology in composite samples based on scanning electron microscopy-energy
      dispersion X-ray spectrometry (SEM-EDX) elemental maps. Benefits are shown for
      applying diffuse reflectance infrared Fourier transform spectroscopy (DRIFTS) vs
      transmittance-FT-IR (T-FT-IR) to analyze organic and inorganic components in
      single samples. Complementary techniques to fully characterize artifacts were gas
      chromatography/mass spectroscopy (GC/MS), optical microscopy (OM), conventional
      powder XRD, and (14)C dating. Bone-hydroxyapatite was detected in the coating.
      Mineralogical transformations in the bricks indicate oven temperatures well above
      1000 degrees C, supporting the hypothesis.

PMID- 19099406
TI  - High density, vertically-aligned carbon nanotube membranes.
AB  - A method is presented to prepare high-density, vertically aligned carbon nanotube
      (VA-CNT) membranes. The CNT arrays were prepared by chemical vapor deposition
      (CVD), and the arrays were collapsed into dense membranes by capillary-forces due
      to solvent evaporation. The average space between the CNTs after shrinkage was
      approximately 3 nm, which is comparable to the pore size of the CNTs. Thus, the
      interstitial pores between CNTs were not sealed, and gas permeated through both
      CNTs and interstitial pores. Nanofiltration of gold nanoparticles and N(2)
      adsorption indicated the pore diameters were approximately 3 nm. Gas permeances,
      based on total membrane area, were 1-4 orders of magnitude higher than VA-CNT
      membranes in the literature, and gas permeabilities were 4-7 orders of magnitude
      higher than literature values. Gas permeances were approximately 450 times those
      predicted for Knudsen diffusion, and ideal selectivities were similar to or
      higher than Knudsen selectivities. These membranes separated a larger molecule
      (triisopropyl orthoformate (TIPO)) from a smaller molecule (n-hexane) during
      pervaporation, possibly due to the preferential adsorption, which indicates
      separation potential for liquid mixtures.

PMID- 19099408
TI  - Nanoaperture-enhanced signal-to-noise ratio in fluorescence correlation
      spectroscopy.
AB  - The fluorescence enhancement found in gold nanoapertures is demonstrated to
      increase the signal-to-noise ratio (SNR) in fluorescence correlation spectroscopy
      (FCS). Starting from a general discussion on noise in FCS experiments, we show
      that fluorescence enhancement leads to a dramatic increase in the SNR. This
      prediction is confirmed by experiments where we report an experimental gain in
      SNR of about 1 order of magnitude, corresponding to a 100-fold reduction of the
      experiment duration. This technique is then applied to monitor the kinetics of a
      fast enzymatic cleavage reaction. This set of experiments evidence the
      feasibility of FCS analysis with fast integration times of about 1 s, opening the
      way to the monitoring of a variety of biochemical reactions at reduced time
      scales.

PMID- 19099409
TI  - Fragmentation of singly protonated peptides via interaction with metastable rare
      gas atoms.
AB  - The effects of metastable energy level and peptide sequence on the fragmentation
      patterns of singly charged peptide ions dissociated in collisions with metastable
      rare gas atoms were studied. Fragmentation spectra of singly charged peptide ions
      were shown to be more structure-informative and very different from those
      obtained in low-energy collision-induced dissociation. Unusual odd-electron
      radical a- and x-ions were observed. Several fragment ions corresponding to a
      side-chain loss were also observed, which allowed differentiation between leucine
      and isoleucine. The fragmentation mechanism depends on electronic energy
      transferred during interaction with metastable gas atoms and proceeds either via
      Penning ionization with formation of radical odd-electron doubly charged
      molecular cation or via high-energy excitation of internal degrees of freedom of
      the peptide cation.

PMID- 19099410
TI  - Palladium-catalyzed cross-coupling reactions of benzyl indium reagents with aryl
      iodides.
AB  - Herein described is an operationally simple procedure for generating benzyl
      indium species from readily available benzyl bromides and indium metal followed
      by in situ palladium-catalyzed coupling with aryl halides. The procedure provides
      diarylmethanes in modest to excellent yield and tolerates a variety of functional
      groups in both coupling partners.

PMID- 19099411
TI  - Palladium-catalyzed decarboxylative coupling of alkynyl carboxylic acids and aryl
      halides.
AB  - 2-Octynoic acid and phenylpropiolic acid were employed for the palladium
      catalyzed decarboxylative coupling reaction and with a variety of aryl halides.
      The former needed 1,4-bis(diphenylphosphino)butane (dppb) as a ligand and the
      latter tri-tert-butylphosphine (P(t)Bu(3)), and both required 2 equiv of tetra-n
      butylammonium fluoride (TBAF) for full conversion. These reactions showed high
      reactivities and tolerance of functional groups such as vinyl, ester, ether,
      ketone, and amine.

PMID- 19099412
TI  - Uroporphyrinogen III synthase mutations related to congenital erythropoietic
      porphyria identify a key helix for protein stability.
AB  - In the present study we have investigated deleterious mutants in the
      uroporphyrinogen III synthase (UROIIIS) that are related to the congenital
      erythropoietic porphyria (CEP). The 25 missense mutants found in CEP patients
      have been cloned, expressed, and purified. Their enzymatic activities have been
      measured relative to wild-type UROIIIS activity. All mutants retain measurable
      activity, consistent with the recessive character of the disease. Most of the
      mutants with a significant decrease in activity involve residues likely
      associated in binding. However, other mutants are fully active, indicating that
      different mechanisms may contribute to enzyme missfunction. UROIIIS is a
      thermolabile enzyme undergoing irreversible denaturation. The unfolding kinetics
      of wild-type UROIIIS and the suite of mutants have been monitored by circular
      dichroism. This analysis allowed the identification of a helical region in the
      molecule, essential to retain the kinetic stability of the folded conformation.
      C73R is found in one-third of CEP patients, and Cys73 is part of this helix. The
      integrated analysis of the enzymatic activity and kinetic stability data is used
      to gain insight in the relationship between defects in UROIIIS sequence and CEP.

PMID- 19099413
TI  - Protein design provides lead(II) ion biosensors for imaging molecular fluxes
      around red blood cells.
AB  - Metalloprotein design and semiconductor nanoparticles have been combined to
      generate a reagent for selective fluorescence imaging of Pb(2+) ions in the
      presence red blood cells. A biosensor system based on semiconductor nanoparticles
      provides the photonic properties for small molecule measurement in and around red
      blood cells. Metalloprotein design was used to generate a Pb(2+) ion selective
      receptor from a protein that is structurally homologous to a protein used
      previously in this biosensing system. Parameters for the Pb(2+) ion binding site
      were derived from crystallographic structures of low molecular weight Pb(2+) ion
      complexes that contain a stereoactive lone pair. When the designed protein was
      produced and attached to ZnS-coated CdSe nanoparticles, two Pb(NO(3))(2)
      associated binding events were observed (2-fold emission decrease; K(A1) = 1 x
      10(9) M(-1); K(A2) = 3.5 x 10(6) M(-1)). The fluorescence response had a 100 pM
      Pb(NO(3))(2) detection limit, while no response was observed with Ca(2+) ions (10
      mM), Zn(2+) ions (100 muM), or Cd(2+) ions (100 muM). Metal ion selectivity
      presumably comes from the coordination geometry selected to favor lone pair
      formation on Pb(2+) ions and electrostatically disfavor tetrahedral coordination.
      Replacement of ZnS-coated CdSe with ZnS-coated InGaP nanoparticles provided
      similar biosensors (100 pM limit of detection; K(A1) = 1 x 10(9) M(-1); K(A2) = 1
      x 10(7) M(-1)) but with excitation/emission wavelengths longer than the major
      absorbance of red blood cell hemoglobin (>620 nm). The InGaP nanoparticle-based
      biosensors provided a 5 nM Pb(NO(3))(2) detection limit in the presence of red
      blood cells. The modularity of the biosensor system provides exchangeable Pb(2+)
      ion detection around red blood cells.

PMID- 19099414
TI  - Gold-catalyzed hydroalkoxylation of alkoxyallenes.
AB  - We report synthesis of allylic acetals via gold-catalyzed hydroalkoxylation of
      alkoxyallenes with alcohols containing primary and secondary alcohols in good to
      excellent yields under mild condition.

PMID- 19099416
TI  - Modeling micelle-templated mesoporous material SBA-15: atomistic model and gas
      adsorption studies.
AB  - We report the development of a realistic molecular model for mesoporous silica
      SBA-15, which includes both the large cylindrical mesopores and the smaller
      micropores in the pore walls. The methodology for modeling the SBA-15 structure
      involves molecular and mesoscale simulations combined with geometrical
      interpolation techniques. First, a mesoscale model is prepared by mimicking the
      synthesis process using lattice Monte Carlo simulations. The main physical
      features of this mesoscale pore model are then carved out of an atomistic silica
      block; both the mesopores and the micropores are incorporated from the mimetic
      simulations. The calculated pore size distribution, surface area, and simulated
      TEM images of the model structure are in good agreement with those obtained from
      experimental samples of SBA-15. We then investigate the adsorption of argon in
      this structure using Grand Canonical Monte Carlo (GCMC) simulations. The
      adsorption results for our SBA-15 model are compared with those for a similar
      model that does not include the micropores; we also compare with results obtained
      in a regular cylindrical pore. The simulated adsorption isotherm for the SBA-15
      model shows semiquantitative agreement with the experimental isotherm for a SBA
      15 sample having a similar pore size. We observe that the presence of the
      micropores leads to increased adsorption at low pressure compared to the case of
      a model without micropores in the pore walls. At higher pressures, for all
      models, the filling proceeds via the monolayer-multilayer adsorption on the
      mesopore surface followed by capillary condensation, which is mainly controlled
      by the mesopore diameter and is not influenced by the presence of the micropores.

PMID- 19099415
TI  - Role of nucleic acid binding in Sir3p-dependent interactions with chromatin
      fibers.
AB  - Recent studies of the mechanisms involved in the regulation of gene expression in
      eukaryotic organisms depict a highly complex process requiring a coordinated
      rearrangement of numerous molecules to mediate DNA accessibility. Silencing in
      Saccharomyces cerevisiae involves the Sir family of proteins. Sir3p, originally
      described as repressing key areas of the yeast genome through interactions with
      the tails of histones H3 and H4, appears to have additional roles in that
      process, including involvement with a DNA binding component. Our in vitro studies
      focused on the characterization of Sir3p-nucleic acid interactions and their
      biological functions in Sir3p-mediated silencing using binding assays, EM
      imaging, and theoretical modeling. Our results suggest that the initial Sir3p
      recruitment is partially DNA-driven, highly cooperative, and dependent on
      nucleosomal features other than histone tails. The initial step appears to be
      rapidly followed by the spreading of silencing using linker DNA as a track.

PMID- 19099417
TI  - Syntheses of heterocyclic ethenyl C-nucleosides for recognition of inverted base
      pairs within the DNA triple helix by stereoselective intramolecular cyclization
      and olefin metathesis.
AB  - Canonical recognition of gene sequences would allow precise means for specific
      genetic intervention. Unfortunately, specific recognition of two of the four
      possible base pairs by triplex-forming oligonucleotide (TFO) as X x T-A and Y x C
      G within a triplex currently remains elusive. A series of C1-ethenyl nucleosides
      have been devised and evaluated extensively for stability and specificity by
      molecular dynamics simulation. A synthesis via olefin metathesis of the
      unprotected heterocycle and a conveniently prepared anomerically pure C1-vinyl 2
      deoxyribofuranose is presented as a significant improvement over a previously
      reported strategy.

PMID- 19099418
TI  - Synthesis and resolution of a multifunctional inherently chiral calix[4]arene
      with an ABCD substitution pattern at the wide rim: the effect of a
      multifunctional structure in the organocatalyst on enantioselectivity in
      asymmetric reactions.
AB  - An efficient synthetic route to inherently chiral calix[4]arenes with an ABCD
      substitution pattern at the wide rim in the cone conformation was developed for
      the first time. For the synthesis of inherently chiral ABCD-type calix[4]arenes,
      first 5,11-dibromo-17-(3,5-dimethylphenyl)-25,26,27,28-tetrapropoxycalix[4]arene
      (9) was prepared as a key intermediate. Then, functionalization of the
      calix[4]arene 9 was examined, and highly regioselective monofunctionalization was
      achieved via selective monolithiation of bromo groups. Various
      multifunctionalized inherently chiral ABCD-type calix[4]arenes can be synthesized
      by using this method; thus, the synthesis of inherently chiral phosphine and
      carboxylic acid derivatives of ABCD-type calix[4]arene was demonstrated. In
      addition, the aminophenol derivative 1b of an ABCD-type calix[4]arene with a 3,5
      dimethylphenyl group at the wide rim was synthesized and resolved into optically
      pure enantiomers. The chiral calix[4]arene 1b was used as an organocatalyst in
      asymmetric Michael addition reactions of thiophenols. The effect of the 3,5
      dimethylphenyl group at the wide rim of calix[4]arene 1b on enantioselectivity
      was examined, and a positive effect of the 3,5-dimethylphenyl group was observed.

PMID- 19099419
TI  - Nonracemizable isocyanoacetates for multicomponent reactions.
AB  - Chiral ortho esters of alpha-isocyano acids were synthesized from commercially
      available Cbz-protected alpha-amino acids. These compounds are stable toward
      racemization in the Ugi 4CC in contrast to known esters of alpha-isocyano acids.
      Applying them in Ugi 4CC with subsequent deprotection gives access to dipeptides
      with preserved configuration at the C-terminal amino acid.

PMID- 19099420
TI  - Protein profilings in mouse liver regeneration after partial hepatectomy using
      iTRAQ technology.
AB  - Liver is unique in its capability to regenerate after an injury. Liver
      regeneration after a 2/3 partial hepatectomy served as a classical model and is
      adopted frequently to study the mechanism of liver regeneration. In the present
      study, semiquantitative analysis of protein expression in mouse liver
      regeneration following partial hepatectomy was performed using an iTRAQ
      technique. Proteins from pre-PHx control livers and livers regenerating for 24,
      48 and 72 h were extracted and inspected using 4-plex isotope labeling, followed
      by liquid chromatography fractionation, mass spectrometry and statistical
      differential analysis. A total of 827 proteins were identified in this study.
      There were 270 proteins for which quantitative information was available at all
      the time points in both biologically duplicate experiments. Among the 270
      proteins, Car3, Mif, Adh1, Lactb2, Fabp5, Es31, Acaa1b and LOC100044783 were
      consistently down-regulated, and Mat1a, Dnpep, Pabpc1, Apoa4, Oat, Hpx, Hp and
      Mt1 were up-regulated by a factor of at least 1.5 from that of the controls at
      one time point or more. The regulation of each differential protein was also
      demonstrated by monitoring its time-dependent expression changes during the
      regenerating process. We believe this is the first report to profile the protein
      changes in liver regeneration utilizing the iTRAQ proteomic technique.

PMID- 19099422
TI  - Influence of the type of oxidant on anion exchange properties of fibrous
      Cladophora cellulose/polypyrrole composites.
AB  - The electrochemically controlled anion absorption properties of a novel large
      surface area composite paper material composed of polypyrrole (PPy) and cellulose
      derived from Cladophora sp. algae, synthesized with two oxidizing agents,
      iron(III) chloride and phosphomolybdic acid (PMo), were analyzed in four
      different electrolytes containing anions (i.e., chloride, aspartate, glutamate,
      and p-toluenesulfonate) of varying size.The composites were characterized with
      scanning and transmission electron microscopy, N2 gas adsorption,and conductivity
      measurements. The potential-controlled ion exchange properties of the materials
      were studied by cyclic voltammetry and chronoamperometry at varying potentials.
      The surface area and conductivity of the iron(III) chloride synthesized sample
      were 58.8 m2/g and 0.65 S/cm, respectively, while the corresponding values for
      the PMo synthesized sample were 31.3 m2/g and 0.12 S/cm. The number of absorbed
      ions per sample mass was found to be larger for the iron(III) chloride
      synthesized sample than for the PMo synthesized one in all four electrolytes.
      Although the largest extraction yields were obtained in the presence of the
      smallest anion (i.e., chloride) for both samples, the relative degree of
      extraction for the largest ions (i.e., glutamate and p-toluenesulfonate) was
      higher for the PMo sample. This clearly shows that it is possible to increase the
      extraction yield of large anions by carrying out the PPy polymerization in the
      presence of large anions. The results likewise show that high ion exchange
      capacities, as well as extraction and desorption rates, can be obtained for large
      anions with high surface area composites coated with relatively thin layers of
      PPy.

PMID- 19099421
TI  - Identification and development of fucosylated glycoproteins as biomarkers of
      primary hepatocellular carcinoma.
AB  - Changes in N-linked glycosylation are known to occur during the development of
      cancer. For example, we have previously reported changes in N-linked
      glycosylation that occur with the development of hepatocellular carcinoma (HCC)
      and, through the use of glycoproteomics, identified many of those proteins
      containing altered glycan structures. To advance these studies and further
      explore the glycoproteome, we performed N-linked glycan analysis from serum
      samples depleted of the major acute phase proteins, followed by targeted lectin
      extraction of those proteins containing changes in glycosylation. Using this
      method, changes in glycosylation, specifically increased amounts of core and
      outer arm fucosylation, were observed in the depleted samples. The identities of
      those proteins containing core and outer arm fucose were identified in the serum
      of patients with HCC. The usefulness of some of these proteins in the diagnosis
      of HCC was determined through the analysis of over 300 patient samples using a
      high-throughput plate based approach. Greatest performance was achieved with
      fucosylated hemopexin, which had an AUROC of 0.9515 with an optimal sensitivity
      of 92% and a specificity of 92%.

PMID- 19099423
TI  - The partially folded homodimeric intermediate of Escherichia coli aspartate
      aminotransferase contains a "molten interface" structure.
AB  - The role of intersubunit side chain-side chain interactions in the stability of
      the Escherichia coli aspartate aminotransferase (eAATase) homodimer was
      investigated by directed mutagenesis at 10 different interface contacts. The urea
      mediated unfolding pathway of this enzyme proceeds through the formation of a
      dimeric intermediate, D*, that retains only 40% of the native enzyme secondary
      structure as judged by circular dichroism. Disruption of any single intersubunit
      interaction results in a >2.6 kcal mol(-1) decrease in native state stability,
      independent of its location or nature. However, the stability of D* with respect
      to U, the unfolded monomer, is the same for all mutants. The stability of the
      eAATase interface cannot be ascribed to the contribution of a few hot spots, or
      to the accumulation of a large number of weak interactions, but only to the
      presence of multiple important and interconnected interactions. It is proposed
      that a "molten interface" structure, flexible enough to accommodate point
      mutations, accounts for the stability of D*. Nuclei of tertiary structure, which
      are not involved in native intersubunit contacts, likely provide a scaffold for
      the unstructured interface of D*. Such a scaffold would account for the
      cooperative unfolding of the intermediate.

PMID- 19099425
TI  - Molecular dynamics simulation of oxygen transport through n-alkanethiolate self
      assembled monolayers on gold and copper.
AB  - Molecular dynamics (MD) simulations were performed to investigate the influence
      of molecular structure on the ability of n-alkanethiolate self-assembled
      monolayers (SAMs) on gold and copper to act as barrier films against through-film
      oxygen transport as relevant to the uses of these films in corrosion inhibition.
      Specific explorations focused on the effects of the packing density of the
      adsorbates, their chain length, and the size of the diffusing species. The MD
      simulations showed that the resistances offered by these monolayers against
      transport of small molecules strongly depend on the penetrant size and that the
      free volume alignment within these films has a large impact on the diffusivities
      of oxygen through them. The MD simulations revealed that the barrier for
      transport through these films increase by approximately 0.3 to 0.6 kJ/mol for
      increases in their thickness of only roughly an angstrom. MD simulations show the
      existence of a middle section in these SAMs for n >or= 12 that was more
      crystalline and dense than the rest of the monolayer. The barrier resistances
      offered by these films toward oxygen transport, as calculated by the MD
      simulations, were a function of the crystallinity, density, and thickness of the
      middle section of the SAMs.

PMID- 19099426
TI  - Kinetics of coloration in photochromic organoammonium polyoxomolybdates.
AB  - The excellent photochromic properties of
      (H(2)DABCO)(2)(HDMA)(0.5)Na(0.75)(H(3)O)(0.75)[Mo(8)O(27)] x 3 H(2)O (4), a new
      member of the (H(2)DABCO)(2)(A)(x)[Mo(8)O(27)] x n H(2)O series, are compared
      with those of (H(2)DABCO)(2)(NH(4))(2)[Mo(8)O(27)] x 4 H(2)O (1),
      (H(2)DABCO)(2)(H(2)pipz)[Mo(8)O(27)] (2), and (H(2)pipz)(3)[Mo(8)O(27)] (3). All
      these powdered materials turn from white to purple under illumination at 365 nm,
      which is associated with photoreduction of Mo(6+) cations into Mo(5+) cations. We
      show that the rates of coloration, which increase in the order 1 < 3, 2 < 4, are
      related to the decrease in the concentration of reducible Mo(6+) centers with
      irradiation time and follow a second-order reaction law because the event of
      light absorption at a reducible Mo(6+) site does not necessarily coincide with
      that of the N(+)-H bond breaking in the N(+)-H...O hydrogen bond associated with
      the Mo(6+) site. First-principles density functional electronic structure
      calculations were carried out to find that this trend correlates with the
      homolytic dissociation energies of the N(+)-H bonds in the organic cations
      HDMA(+), H(2)pipz(2+), H(2)DABCO(2+), and NH(4)(+). This observation is
      consistent with a photochromic mechanism based on the homolytic cleavage of N(+)
      H bonds rather than on the heterolytic cleavage of N(+)-H bonds.

PMID- 19099427
TI  - Novel three-component route to diastereoselective synthesis of trisubstituted
      vinylphosphonates using phosphites, acetylenic esters, and aroyl chlorides.
AB  - Trisubstituted vinylphosphonates have been prepared via three-component reaction
      using phosphites, acetylenic esters, and aroyl chlorides in good yields. A
      variety of phosphites, activated acetylenes, and aroyl chlorides have been
      successfully employed in these reactions. In addition, three-component synthesis
      of vinylphosphonate provides exclusive E-olefin stereochemistry.

PMID- 19099428
TI  - Theoretical and spectroscopic investigations of the bonding and reactivity of
      (RO)3M[triple bond]N molecules, where M = Cr, Mo, and W.
AB  - The electronic structures of the molecules ((t)BuO)(3)M[triple bond]N (M = Cr,
      Mo, W) have been investigated with gas phase photoelectron spectroscopy and
      density functional calculations. It is found that the alkoxide orbitals mix
      strongly with the M[triple bond]N triple bond orbitals and contribute
      substantially to the valence electronic structure. The first ionization of
      ((t)BuO)(3)Cr[triple bond]N is from an orbital of a(2)(C(3v)) symmetry that is
      oxygen based and contains no metal or nitrogen character by symmetry. In
      contrast, the first ionizations of the molybdenum and tungsten analogues are from
      orbitals of a(1) and e symmetry that derive from the highest occupied M[triple
      bond]N sigma and pi orbitals mixed with the appropriate symmetry combinations of
      the oxygen p orbitals. In this a(1) orbital, the oxygen p orbitals mix with the
      highest occupied M[triple bond]N orbital of sigma symmetry. This mixing reduces
      the metal character, consequently reducing the metal-nitrogen overlap interaction
      in this orbital. From computational modeling, the polarity of the M[triple bond]N
      bond increases down the group such that W[triple bond]N has the highest charge
      separation. In addition to investigation of the effects of the metals, the
      electronic influences of substitution at the alkoxide ligands have been examined
      for the molecules (RO)(3)Mo[triple bond]N (R = C(CH(3))(2)H, C(CH(3))(3), and
      C(CH(3))(2)CF(3)). The introduction of CF(3) groups stabilizes the molecular
      orbital energies and increases the measured ionization energies, but does not
      alter the overall electronic structure. The bonding characteristics of the
      ((t)BuO)(3)M[triple bond]N series are compared with those of organic nitriles.

PMID- 19099429
TI  - Characterization of nonionic microemulsions by EPR. Part II. The effect of
      competitive solubilization of cholesterol and phytosterols on the nanostructure.
AB  - One of the theories for the reduction of cholesterol (CH) in the blood stream by
      the consumption of phytosterols (PS) states that these two types of sterols
      compete for solubilization within the dietary mixed micelles (DMM). In this
      study, a fully dilutable nonionic microemulsion system was used as a model to
      explain a possible competitive solubilization mechanism of CH and PS molecules
      using an electron paramagnetic resonance (EPR) technique that reveals relevant
      intramicellar properties. The effect of the solubilized sterols on the structural
      changes occurring in the vicinity of the surfactant head groups or closer to the
      oil phase was examined by controlling the pH of the environment, which influences
      the probe locus between the surfactant molecules. The results indicate that the
      structure transformations in the surfactant layer closer to the vicinity of the
      head groups region are more pronounced than the structural changes occurring in
      the region between the surfactant tails closer to the oil phase, except for the
      oil-in-water (O/W) micelles region. The study also shows that when each of the
      sterols is solubilized alone, they occupy different solubilization sites within
      the microemulsion nanostructures, in comparison to their solubilization together.
      This behavior is most pronounced in 3:1 (wt ratio) CH/PS systems. The main
      conclusion is that cosolubilization of these sterols leads to competitive
      solubilization between the surfactant tails closer to the oil phase locus, where
      the CH molecules are pushed toward the interface by the PS molecules. This
      conclusion might better explain the competitive solubilization of the two sterols
      in the human digestive tract.

PMID- 19099430
TI  - Solubilization of naphthalene in the presence of plant-synthetic mixed surfactant
      systems.
AB  - Solubilization efficiencies of naphthalene by micellar solution of a plant-based
      surfactant extracted from fruit of Sapindus mukorossi (reetha) and the synthetic
      surfactants like nonionic (Triton X-100 or TX-100), cationic
      (cetyltrimethylammonium bromide or CTAB), and anionic (sodium
      dodecylbenzenesulfonate or SDBS; dioctyl sodium sulfosuccinate or AOT; sodium
      octanesulfonate or SOS) in their single and as well as binary mixed (plant
      synthetic) systems were measured and compared. The solubilization efficiency of
      single surfactants shows that reetha is less effective than TX-100, similar to
      SDBS, and more than AOT and SOS. The mixed surfactant systems show negative
      deviation in molar solubilization ratio (MSR) from ideality. The ascending order
      of percent change in MSR (Delta(MSR)) is TX-100-reetha < CTAB-reetha < SDBS
      reetha < AOT-reetha < SOS-reetha. The mixed micellar solution for a particular
      combination also shows that Delta(MSR) is more negative when the interaction
      parameter for the mixed micelle (beta) is more negative. The results of this
      study may be useful for the applications of natural or natural-synthetic mixed
      surfactants in surfactant-enhanced remediation or detergency.

PMID- 19099431
TI  - Preparation and characterization of chemically functionalized silica-coated
      magnetic nanoparticles as a DNA separator.
AB  - The work describes a simple and convenient process for highly efficient and
      direct DNA separation with functionalized silica-coated magnetic nanoparticles.
      Iron oxide magnetic nanoparticles and silica-coated magnetic nanoparticles were
      prepared uniformly, and the silica coating thickness could be easily controlled
      in a range from 10 to 50 nm by changing the concentration of silica precursor
      (TEOS) including controlled magnetic strength and particle size. A change in the
      surface modification on the nanoparticles was introduced by aminosilanization to
      enhance the selective DNA separation resulting from electrostatic interaction.
      The efficiency of the DNA separation was explored via the function of the amino
      group numbers, particle size, the amount of the nanoparticles used, and the
      concentration of NaCl salt. The DNA adsorption yields were high in terms of the
      amount of triamino-functionalized nanoparticles used, and the average particle
      size was 25 nm. The adsorption efficiency of aminofunctionalized nanoparticles
      was the 4-5 times (80-100%) higher compared to silica-coated nanoparticles only
      (10-20%). DNA desorption efficiency showed an optimum level of over 0.7 M of the
      NaCl concentration. To elucidate the agglomeration of nanoparticles after
      electrostatic DNA binding, the Guinier plots were calculated from small-angle X
      ray diffractions in a comparison of the results of energy diffraction TEM and
      confocal laser scanning microscopy. Additionally, the direct separation of human
      genomic DNA was achieved from human saliva and whole blood with high efficiency.

PMID- 19099433
TI  - First solvation shell effects on ionic chemical reactions: new insights for
      supramolecular catalysis.
AB  - This article presents a detailed discussion on medium effect on ionic S(N)2
      reactions. Ion pairing and the first solvation shell play the main role on
      reactivity. Ab initio calculations are used to show that a combination of apolar
      molecular cavity with polar hydroxyl groups can have catalytic effects on these
      reactions. The present results open an avenue of development for supramolecular
      catalysts able to control bimolecular ionic reactions. In particular, this new
      catalytic concept could be useful in nucleophilic fluorinations.

PMID- 19099435
TI  - Tracking spatial disorder in an optical ruler by time-resolved NSET.
AB  - For biomolecular applications, potential interactions between newly developed dye
      molecules and the biomolecule of interest can dramatically influence the accuracy
      of optical ruler techniques. By utilizing nanometal surface energy transfer
      (NSET), an optical technique is developed that allows the nature of interactions
      between dyes and a biomolecule, namely DNA, to be directly assessed. To
      demonstrate the method, interactions between well-known molecular dyes based on
      carboxyfluorescein (FAM, noninteracting) and Cy5 (known intercalator) with DNA is
      probed. The results demonstrate that FAM exhibits no interactions with the DNA
      backbone and is adequately represented as a solvent exposed dye, while the
      commonly used near-IR dye Cy5 exhibits two discrete interactions that depend on
      the site of appendage and the length of the linker arm. The exact population and
      nature of Cy5 interaction with the DNA indicates a 37% ratio of intercalation for
      the internal C(6), a 42% ratio for an internal C(3) spacer length, and no
      evidence of interaction for terminal labeling. The results allow quantitative
      assignment of the site occupation of donors to be analyzed providing a powerful
      set of information for use of dyes in FRET based optical ruler technologies
      without the need of single molecule methods or the assumption of an averaged site
      occupation for the donor.

PMID- 19099434
TI  - Pyrenebutyrate-mediated delivery of quantum dots across the plasma membrane of
      living cells.
AB  - Quantum dots have been delivered directly across the plasma membrane to the
      cytosol of living cells using a combination of a cationic peptide, polyarginine,
      and a hydrophobic counterion, pyrenebutyrate. Quantum dot delivery did not
      disrupt the plasma membrane and bypassed the barrier of endocytic vesicles.
      Cellular uptake was independent of temperature but highly dependent on the
      surface charge of the quantum dot and the membrane potential of the cell,
      suggesting a direct translocation across the membrane. This method of delivery
      can find immediate application for quantum dots and may be broadly applicable to
      other nanoparticles.

PMID- 19099436
TI  - Comparison of the structure and dynamics of the antibiotic peptide polymyxin B
      and the inactive nonapeptide in aqueous trifluoroethanol by NMR spectroscopy.
AB  - The structure and dynamics of polymyxin B (PxB), an N-acylated cyclic decapeptide
      that displays antimicrobial activity against Gram-negative bacteria, is
      characterized by NMR and compared to results for the inactive nonapeptide, which
      is missing the N-terminal amino acid along with the attached acyl chain. Aqueous
      trifluoroethanol (TFE) was chosen as the solvent since the overall structure of
      PxB in TFE is similar to the structure when bound to vesicles. No differences
      were observed between the two peptides for (1)H H(alpha) chemical shifts or
      patterns of cross peaks in NOESY spectra, indicating that the overall structures
      are quite similar. The sign and intensity of NOESY spectra obtained at different
      temperatures were used to assess the relative mobility of the peptides. For both
      peptides, differential mobility is observed in different parts of the molecule,
      with greater mobility observed for the linear portion than the ring and faster
      motion seen for the side chains than the peptide backbone. However, all motion is
      faster in the nonapeptide, indicating that the presence of the N-terminal acyl
      chain restricts the mobility of PxB compared to the nonapeptide, which lacks this
      structural feature. For both peptides, differential mobility is also observed
      within the cyclic portion of the peptide. This supports a proposed model whereby
      the more rigid residues serve as pivot points, allowing the ring conformation to
      change in response to different binding partners. However, conformational
      flexibility within the cyclic ring is not sufficient for antimicrobial activity
      since both the active and inactive peptides exhibit the same flexibility. The N
      terminal acyl chain on PxB, which is essential for activity, exhibits rapid,
      independent motion, and this flexibility may facilitate penetration of the outer
      membrane.

PMID- 19099438
TI  - Microemulsions with an ionic liquid surfactant and room temperature ionic liquids
      as polar pseudo-phase.
AB  - In this investigation we present for the first time microemulsions comprising an
      ionic liquid as surfactant and a room-temperature ionic liquid as polar pseudo
      phase. Microemulsions containing the long- chain ionic liquid1-hexadecyl-3-methyl
      imidazolium chloride ([C16mim][Cl]) as surfactant, decanol as cosurfactant,
      dodecaneas continuous phase and room temperature ionic liquids (ethylammonium
      nitrate (EAN) and 1-butyl-3-methylimidazolium tetrafluoroborate ([bmim]][BF4]),
      respectively) as polar microenvironment have been formulated. The phase diagrams
      of both systems were determined at a constant surfactant/cosurfactant molar
      ratio. EAN microregions in oil have been confirmed with conductivity
      measurements. In presence of EAN a model of dynamic percolation could be applied.
      Dynamic light scattering (DLS) measurements indicated a swelling of the formed
      nano-structures with increasing amount of EAN, a linear dependence of the
      hydrodynamic radii on the EAN weight fraction was observed. Both systems
      exhibited a single broad peakin SAXS and follow a characteristic q-4 dependence
      of the scattering intensity at large q values. The Teubner-Strey model was
      successfully used to fit the spectra giving fa, the amphiphilic factor, and the
      two characteristic length scales of microemulsions, namely the periodicity, d,
      and the correlation length, zeta. Furthermore, the specific area of the interface
      could be determined from the Porod limit and the experimental invariant. The
      amphiphilic factor clearly demonstrated structural differences between the two
      systems confirming that the nature of the polar ionic liquid plays an important
      role on the rigidity of the interfacial film. The adaptability of three different
      models ranging from spherical ionic liquid in oil over repulsive spheres to
      bicontinuous structures has been checked.

PMID- 19099437
TI  - Synchronous vs asynchronous chain motion in alpha-synuclein contact dynamics.
AB  - alpha-Synuclein (alpha-syn) is an intrinsically unstructured 140-residue neuronal
      protein of uncertain function that is implicated in the etiology of Parkinson's
      disease. Tertiary contact formation rate constants in alpha-syn, determined from
      diffusion-limited electron-transfer kinetics measurements, are poorly
      approximated by simple random polymer theory. One source of the discrepancy
      between theory and experiment may be that interior-loop formation rates are not
      well approximated by end-to-end contact dynamics models. We have addressed this
      issue with Monte Carlo simulations to model asynchronous and synchronous motion
      of contacting sites in a random polymer. These simulations suggest that a
      dynamical drag effect may slow interior-loop formation rates by about a factor of
      2 in comparison to end-to-end loops of comparable size. The additional deviations
      from random coil behavior in alpha-syn likely arise from clustering of
      hydrophobic residues in the disordered polypeptide.

PMID- 19099439
TI  - Synthesis, spectroscopy and structure of the parent furoxan (HCNO)2.
AB  - The parent furoxan (1,2,5-oxadiazole 2-oxide), synthesized from glyoxime and
      NO(2)(g), has been investigated in the gas phase for the first time by mid
      infrared and He I photoelectron spectroscopy, and in the liquid phase by Raman
      spectroscopy. The ground-state geometry has been obtained from quantum-chemical
      calculations at the B3LYP, MPn (n = 2-4), CISD, QCISD, CCSD, CCSD(T), RSPTn (n =
      2,3), MRCI, and MR-AQCC levels using 6-311++G(2d,2p), cc-pVTZ, aug-cc-pVTZ, cc
      pCVTZ, and cc-pVQZ basis sets. Furoxan is predicted to be planar, with a strong
      exocyclic and a relatively weak endocyclic N-O bond. The furoxan moiety is
      electron rich, indicated e.g. by a large negative NPA charge (-0.46 e). According
      to various aromaticity indices, furoxan is nearly as aromatic as furan and
      furazan. Unlike alkyl- and cyano-substituted furoxans, the parent furoxan, upon
      thermolysis, does not cleave to the monomer nitrile oxide, yielding only HNCO,
      HCN, CO(2), CO, NO, and H(2)O decomposition products.

PMID- 19099440
TI  - Effect of periodic replacement of the heteroatom on the spectroscopic properties
      of indole and benzofuran derivatives.
AB  - The electronic structures of a homologous series of indole and benzofuran
      derivatives, in which the nitrogen or oxygen atom is replaced by group 15 and
      group 16 heavier heteroatoms, have been investigated by means of various
      spectroscopic techniques coupled with density functional calculations. It was
      found that the excitation energies of the group 16 benzoheteroles systematically
      shift to the red in the order of benzofuran (6), benzothiophene (7),
      benzoselenophene (8), and benzotellurophene (9). In contrast, the electronic
      absorption spectra of the group 15 benzoheteroles, 1-phenyl derivatives of indole
      (1b), phosphindole (2b), arsindole (3b), stibindole (4b), and bismuindole (5b),
      did not exhibit this type of spectral shift. X-ray analysis and density
      functional theory (DFT) studies revealed that 2b-5b adopt a bent conformation
      both in the crystalline and in the solution phases. In contrast, planar
      structures were calculated for the group 16 heterocycles. Using the observed
      spectroscopic properties and time-dependent density functional theory (TDDFT)
      calculations, the electronic absorption spectra of the present heterocycles were
      assigned. A molecular orbital analysis was performed to rationalize the effect of
      replacement of the heteroatom on the electronic structures. The observed magnetic
      circular dichroism (MCD) sign patterns of these heterocycles are interpreted
      according to Michl's perimeter model.

PMID- 19099441
TI  - Infrared spectra and theoretical calculations for Fe, Ru, and Os metal hydrides
      and dihydrogen complexes.
AB  - Laser-ablated iron, ruthenium, and osmium atoms react with hydrogen in excess
      argon, neon and pure hydrogen to produce the FeH(2) molecule, and the
      FeH(2)(H(2))(3), RuH(H(2))(4), RuH(2)(H(2))(4), and (H(2))MH complexes (M = Fe,
      Ru, Os), as identified through infrared spectra with D(2) and HD substitution.
      DFT frequency calculations support the assignment of absorptions observed
      experimentally. The FeH(2) molecule has a quintet ground state with a quasi
      linear structure, and is repulsive to the addition of one more H(2) ligand:
      however, with three more H(2) ligands, stable triplet and singlet state
      FeH(2)(H(2))(3) supercomplexes can be formed. The quintet FeH(2) molecule and
      FeH(2)(H(2))(3) supercomplex undergo reversible near-ultraviolet photochemical
      rearrangement in solid neon and hydrogen. The RuH(2) molecule has a bent triplet
      ground state and forms the stable singlet RuH(2)(H(2))(4) supercomplex, but only
      the latter is observed in these experiments. In like fashion RuH has a quartet
      ground state and the doublet RuH(H(2))(4) complex is trapped in solid hydrogen.
      All three (H(2))MH complexes with lower energy than MH(3) are trapped, and no
      absorptions are observed for MH(3) molecules.

PMID- 19099442
TI  - Electronic structure of disordered conjugated polymers: polythiophenes.
AB  - Electronic structure of disordered semiconducting conjugated polymers was
      studied. Atomic structure was found from a classical molecular dynamics
      simulation, and the charge patching method was used to calculate the electronic
      structure with the accuracy similar to the one of density functional theory in
      local density approximation. The total density of states, the local density of
      states at different points in the system, and the wave functions of several
      states around the gap were calculated in the case of poly(3-hexylthiophene)
      (P3HT) and polythiophene (PT) systems to gain insight into the origin of disorder
      in the system, the degree of carrier localization, and the role of chain
      interactions. The results indicated that disorder in the electronic structure of
      alkyl-substituted polythiophenes comes from disorder in the conformation of
      individual chains, while in the case of polythiophene there is an additional
      contribution due to disorder in the electronic coupling between the chains. Each
      of the first several wave functions in the conduction and valence band of P3HT is
      localized over several rings of a single chain. It was shown that the
      localization can be caused in principle both by ring torsions and chain bending;
      however, the effect of ring torsions is much stronger. PT wave functions are more
      complicated due to larger interchain electronic coupling and are not necessarily
      localized on a single chain.

PMID- 19099443
TI  - Luminescent cyclometalated iridium(III) polypyridine indole complexes--synthesis,
      photophysics, electrochemistry, protein-binding properties, cytotoxicity, and
      cellular uptake.
AB  - A series of luminescent cyclometalated iridium(III) polypyridine indole
      complexes, [Ir(N--C)(2)(N--N)](PF(6)) (HN--C = 2-phenylpyridine (Hppy), N--N = 4
      ((2-(indol-3-yl)ethyl)aminocarbonyl)-4'-methyl-2,2'-bipyridine (bpy-ind) (1a), N-
      N = 4-((5-((2-(indol-3-yl)ethyl)aminocarbonyl)pentyl)aminocarbonyl)-4'-methyl
      2,2'-bipyridine (bpy-C6-ind) (1b); HN--C = 7,8-benzoquinoline (Hbzq), N--N = bpy
      ind (2a), N--N = bpy-C6-ind (2b); and HN--C = 2-phenylquinoline (Hpq), N--N = bpy
      ind (3a), N--N = bpy-C6-ind (3b)), have been synthesized, characterized, and
      their photophysical and electrochemical properties and lipophilicity
      investigated. Photoexcitation of the complexes in fluid solutions at 298 K and in
      alcohol glass at 77 K resulted in intense and long-lived luminescence (lambda(em)
      = 540-616 nm, tau(o) = 0.13-5.15 mus). The emission of the complexes has been
      assigned to a triplet metal-to-ligand charge-transfer ((3)MLCT) (dpi(Ir) -->
      pi*(N--N)) excited state, probably with some mixing of triplet intraligand
      ((3)IL) (pi --> pi*) (pq) character for complexes 3a,b. Electrochemical
      measurements revealed that all the complexes showed an irreversible indole
      oxidation wave at ca. +1.1 V versus SCE, a quasi-reversible iridium(IV/III)
      couple at ca. +1.3 V, and a reversible diimine reduction couple at ca. -1.3 V.
      The interactions of these complexes with an indole-binding protein, bovine serum
      albumin (BSA), have been studied by emission titrations, and the K(a) values are
      on the order of 10(4) M(-1). Additionally, the cytotoxicity of the complexes
      toward human cervix epithelioid carcinoma (HeLa) cells has been examined by the 3
      (4,5-dimethyl-2-thiazolyl)-2,5-diphenyltetrazolium bromide (MTT) assay. The
      IC(50) values of the complexes ranged from 1.1 to 6.3 microM, which are
      significantly smaller than that of cisplatin (30.7 microM) under the same
      experimental conditions. Furthermore, the cellular uptake of the complexes has
      been investigated by flow cytometry and laser-scanning confocal microscopy. The
      microscopy images indicated that complex 3a was localized in the perinuclear
      region upon interiorization. Temperature-dependence experiments suggested that
      the internalization of the complex was an energy-requiring process such as
      endocytosis. This has been confirmed by cellular-uptake experiments involving the
      luminescent conjugates Ir-BSA and Ir-TF (TF = holo-transferrin), which were
      prepared by conjugation of the proteins with the complex [Ir(pq)(2)(phen
      NCS)](PF(6)) (phen-NCS = 5-isothiocyanato-1,10-phenanthroline).

PMID- 19099444
TI  - Unprecedented self-catenated eight-connected network based on novel azide-bridged
      tetramanganese(II) clusters.
AB  - The combination of the azide bridge and a neutral inner-salt-type dicarboxylate
      ligand leads to a three-dimensional coordination framework that contains
      unprecedented azide-bridged tetramanganese(II) clusters and defines a novel self
      catenated, eight-connected net of 4(16) x 6(12) topology.

PMID- 19099445
TI  - Probing the catalytic mechanism of S-ribosylhomocysteinase (LuxS) with catalytic
      intermediates and substrate analogues.
AB  - S-Ribosylhomocysteinase (LuxS) cleaves the thioether bond in S
      ribosylhomocysteine (SRH) to produce homocysteine (Hcys) and 4,5-dihydroxy-2,3
      pentanedione (DPD), the precursor of the type II bacterial quorum sensing
      molecule (AI-2). The catalytic mechanism of LuxS comprises three distinct
      reaction steps. The first step involves carbonyl migration from the C1 carbon of
      ribose to C2 and the formation of a 2-ketone intermediate. The second step shifts
      the C=O group from the C2 to C3 position to produce a 3-ketone intermediate. In
      the final step, the 3-ketone intermediate undergoes a beta-elimination reaction
      resulting in the cleavage of the thioether bond. In this work, the 3-ketone
      intermediate was chemically synthesized and shown to be chemically and
      kinetically competent in the LuxS catalytic pathway. Substrate analogues
      halogenated at the C3 position of ribose were synthesized and reacted as time
      dependent inhibitors of LuxS. The time dependence was caused by enzyme-catalyzed
      elimination of halide ions. Examination of the kinetics of halide release and
      decay of the 3-ketone intermediate catalyzed by wild-type and mutant LuxS enzymes
      revealed that Cys-84 is the general base responsible for proton abstraction in
      the three reaction steps, whereas Glu-57 likely facilitates substrate binding and
      proton transfer during catalysis.

PMID- 19099446
TI  - Solvent effects on the conformational preferences of serotonin: serotonin
      (H(2)O)(n), n = 1,2.
AB  - Neutral serotonin-(H(2)O)(n) clusters with n = 1,2 have been studied under jet
      cooled conditions using a combination of resonant two-photon ionization (R2PI),
      UV-UV hole-burning (UVHB), and resonant ion-dip infrared (RIDIR) spectroscopy.
      Serotonin (5-hydroxytryptamine, SERO) is a close analogue of tryptamine,
      differing by the addition of an OH substituent in the 5-position on the indole
      ring, but sharing the same ethylamine side chain in the 3-position. Three
      conformational isomers of SERO-(H(2)O)(1) were observed via UVHB, with S(0)-S(1)
      origins at 32 671 (A), 32 454 (B), and 32 188 cm(-1) (C). RIDIR spectroscopy
      provided infrared spectra in the hydride stretch region that reflected the
      hydrogen-bonding arrangement of each conformer. Two of the three SERO-(H(2)O)(1)
      conformers have RIDIR spectra nearly identical to that of the only observed
      conformer of tryptamine-(H(2)O)(1), differing only in the orientation of the 5-OH
      group (syn vs anti). In this structure, the H(2)O molecule acts as H-bond donor
      to the NH(2) group on the ethylamine side chain, which is configured in the
      Gpy(out) conformation that is the global minimum in the absence of water.
      Comparison of the OH stretch RIDIR spectrum of the third SERO-(H(2)O)(1)
      conformer with calculation leads to its assignment to a structure in which the
      water molecule forms a H-bonded bridge between the amino group and the 5-OH group
      of SERO, with the ethylamine side chain in the Gph(out) conformation that
      facilitates bridge formation, corresponding to the second most populated
      conformer in the isolated SERO monomer. The OH and CH stretch infrared
      absorptions for the single observed conformer of SERO-(H(2)O)(2) indicate that it
      is also a bridge structure linking the NH(2) and OH groups of SERO, retaining the
      same Gph(out) ethylamine conformation as in conformer C of SERO-(H(2)O)(1). The
      ultraviolet and infrared spectroscopy reflect the fact that the single-water
      bridge cannot optimally span the gap between the 5-OH and NH(2) groups, while the
      water dimer bridge forms a set of three strong H-bonds that lock in the Gph(out)
      ethylamine and anti 5-OH orientations in a near-optimal configuration.

PMID- 19099447
TI  - Cluster and solute velocity distributions in free-jet expansions of supercritical
      CO(2).
AB  - The free-jet expansions of high-pressure CO(2) supercritical solutions are probed
      by direct sampling mass spectrometry. Both cluster intensity measurements and
      velocity distribution measurements are reported for expansions which result in
      cluster formation by condensation and fragmentation of supersaturated vapors and
      superheated liquids. The resulting velocity distributions for these highly
      nonequilibrated expansions are characterized by up to three different peaks,
      depending on the source conditions: two primary peaks associated with very large
      clusters, the slower of which is associated with liquid fragmentation, and a
      smaller faster peak associated with monomers and small CO(2) clusters. We have
      associated the slow peak, observed only for fragmentation of superheated liquid
      expansions, with a liquid or condensed phase fragment by measuring the velocity
      distribution of low vapor pressure solutes in the expansion of supercritical
      CO(2) mixtures.

PMID- 19099448
TI  - Theoretical study of ethylbenzenium ions: the mechanism for splitting off ethene,
      and the formation of a pi complex of ethene and the benzenium ion.
AB  - Structures and energies of protonated ethylbenzene and 2,6-dimethylethylbenzene
      have been studied by quantum chemical calculations. The main goal is to study the
      mechanism for splitting off ethene from protonated ethylbenzene. Data are
      reported for the four ethylbenzenium isomers arising depending on the position of
      the proton on the benzene ring: a pi complex where ethene is weakly bonded to a
      benzenium ion and two transition states connected with the cleavage of the
      ethylbenzenium ion. The larger part of the data that are reported has been
      obtained at the B3LYP/cc-pVTZ level of theory. Energies obtained by the Gaussian
      3 G3B3 composite method are also given. Computations have also been carried out
      at the MP2/6-311++G(d,p) level of theory. The calculated results can be
      reconciled with published experimental observations, and they give information
      about the reaction system that is not obtained by experimental techniques.

PMID- 19099449
TI  - Specific rate constants k(E) of the dissociation of the halobenzene ions:
      analysis by statistical unimolecular rate theories.
AB  - Specific rate constants k(E) of the dissociation of the halobenzene ions C6H5X+ -
      > C6H5+ + X* (X* = Cl, Br, and I) were measured over a range of 10(3)-10(7) s-1
      by threshold photoelectron-photoion coincidence (TPEPICO) spectroscopy. The
      experimental data were analyzed by various statistical unimolecular rate theories
      in order to derive the threshold energies E0. Although rigid activated complex
      RRKM theory fits the data in the experimentally measured energy range, it
      significantly underestimates E0 for chloro- and bromobenzene. Phase space theory
      (PST) does not fit the experimentally measured rates. A parametrized version of
      the variational transition state theory (VTST) as well as a simplified version of
      the statistical adiabatic channel model (SSACM) incorporating an energy dependent
      rigidity factor provide excellent fits to the experimental data and predict the
      correct dissociation energies. Although both approaches have just two adjustable
      parameters, one of which is E0, SSACM is effective and particularly simple to
      apply.

PMID- 19099451
TI  - Self-supported catalysts.

PMID- 19099450
TI  - Camptothecins: a SAR/QSAR study.

PMID- 19099452
TI  - Dendrimers in oncology: an expanding horizon.

PMID- 19099454
TI  - Quantum dot behavior in graphene nanoconstrictions.
AB  - Graphene nanoribbons display an imperfectly understood transport gap. We measure
      transport through nanoribbon devices of several lengths. In long (>/=250 nm)
      nanoribbons we observe transport through multiple quantum dots in series, while
      shorter (</=60 nm) constrictions display behavior characteristic of single and
      double quantum dots. New measurements indicate that dot size may scale with
      constriction width. We propose a model where transport occurs through quantum
      dots that are nucleated by background disorder potential in the presence of a
      confinement gap.

PMID- 19099453
TI  - Proton environment of reduced Rieske iron-sulfur cluster probed by two
      dimensional ESEEM spectroscopy.
AB  - The proton environment of the reduced [2Fe-2S] cluster in the water-soluble head
      domain of the Rieske iron-sulfur protein (ISF) from the cytochrome bc(1) complex
      of Rhodobacter sphaeroides has been studied by orientation-selected X-band 2D
      ESEEM. The 2D spectra show multiple cross-peaks from protons, with considerable
      overlap. Samples in which (1)H(2)O water was replaced by (2)H(2)O were used to
      determine which of the observed peaks belong to exchangeable protons, likely
      involved in hydrogen bonds in the neighborhood of the cluster. By correlating the
      cross-peaks from 2D spectra recorded at different parts of the EPR spectrum,
      lines from nine distinct proton signals were identified. Assignment of the proton
      signals was based on a point-dipole model for interaction with electrons of
      Fe(III) and Fe(II) ions, using the high-resolution structure of ISF from Rb.
      sphaeroides. Analysis of experimental and calculated tensors has led us to
      conclude that even 2D spectra do not completely resolve all contributions from
      nearby protons. Particularly, the seven resolved signals from nonexchangeable
      protons could be produced by at least 13 protons. The contributions from
      exchangeable protons were resolved by difference spectra ((1)H(2)O minus
      (2)H(2)O), and assigned to two groups of protons with distinct anisotropic
      hyperfine values. The largest measured coupling exceeded any calculated value.
      This discrepancy could result from limitations of the point dipole approximation
      in dealing with the distribution of spin density over the sulfur atoms of the
      cluster and the cysteine ligands, or from differences between the structure in
      solution and the crystallographic structure. The approach demonstrated here
      provides a paradigm for a wide range of studies in which hydrogen-bonding
      interactions with metallic centers has a crucial role in understanding the
      function.

PMID- 19099455
TI  - Fluorescent silica nanoparticles with efficient urinary excretion for
      nanomedicine.
AB  - The development of molecularly targeted probes that exhibit high biostability,
      biocompatibility, and efficient clearance profiles is key to optimizing
      biodistribution and transport across biological barriers. Further, coupling
      probes designed to meet these criteria with high-sensitivity, quantitative
      imaging strategies is mandatory for ensuring early in vivo tumor detection and
      timely treatment response. These challenges have often only been examined
      individually, impeding the clinical translation of fluorescent probes. By
      simultaneously optimizing these design criteria, we created a new generation of
      near-infrared fluorescent core-shell silica-based nanoparticles (C dots) tuned to
      hydrodynamic diameters of 3.3 and 6.0 nm with improved photophysical
      characteristics over the parent dye. A neutral organic coating prevented
      adsorption of serum proteins and facilitated efficient urinary excretion.
      Detailed particle biodistribution studies were performed using more quantitative
      ex vivo fluorescence detection protocols and combined optical-PET imaging. The
      results suggest that this new generation of C dots constitutes a promising
      clinically translatable materials platform which may be adapted for tumor
      targeting and treatment.

PMID- 19099457
TI  - Near-infrared reflectance models for the rapid prediction of quality of brewing
      raw materials.
AB  - Calibration models for quickly and reliably predicting moisture content and total
      nitrogen, both "as is" and "dry matter" on malt, as well as moisture content and
      total lipids, both "as is" and "dry matter", on maize by means of near-infrared
      (NIR) spectroscopy were developed. The FT-NIR spectra recorded on the finely
      ground cereals were correlated to the analytical data by means of the
      multivariate PLS algorithm. In particular, these models were developed on the raw
      materials, which are used by the main Italian brewing industries. Validation was
      carried out both by means of cross-validation and test set validation. Regression
      coefficients (R(2)) were higher than 97 for both malt and maize moisture content
      and higher than 85 and 88 for malt total nitrogen and maize total lipids,
      respectively. The RMSE values (both RMSECV and RMSEP) were lower than 0.1% m/m
      for both malt and maize moisture contents, whereas they ranged from 0.024 to
      0.042% m/m for malt total nitrogen and from 0.042 to 0.055% m/m for maize total
      lipids. Repeatability was tested by taking into account more than one sample for
      each calibration and compared, when possible, to those of the standard methods.
      Repeatability (r(95)) ranged from 0.060 to 0.158% m/m and from 0.020 to 0.055%
      m/m for malt moisture and total nitrogen contents, respectively, and from 0.094
      to 0.160% m/m and from 0.076 to 0.208% m/m for maize moisture and total lipids
      contents, respectively.

PMID- 19099456
TI  - Synthesis, spectroscopy, crystal structure, electrochemistry, and quantum
      chemical and molecular dynamics calculations of a 3-anilino difluoroboron
      dipyrromethene dye.
AB  - An asymmetrically substituted fluorescent difluoroboron dipyrromethene (BODIPY)
      dye, with a phenylamino group at the 3-position of the BODIPY chromophore, has
      been synthesized by nucleophilic substitution of 3,5-dichloro-8-(4-tolyl)-4,4
      difluoro-4-bora-3a,4a-diaza-s-indacene. The solvent-dependent spectroscopic and
      photophysical properties have been investigated by means of UV-vis
      spectrophotometry and steady-state and time-resolved fluorometry and reflect the
      large effect of the anilino substituent on the fluorescence characteristics. The
      compound has a low fluorescence quantum yield in all but the apolar solvents
      cyclohexane, toluene, and chloroform. Its emission maxima in a series of solvents
      from cyclohexane to methanol are red-shifted by approximately 50 nm in comparison
      to classic BODIPY derivatives. Its oxidation potential in dichloromethane is at
      ca. 1.14 V versus Ag/AgCl. The absorption bandwidths and Stokes shifts are much
      larger than those of typical, symmetric difluoroboron dipyrromethene dyes. The
      values of the fluorescence rate constant are in the (1.4-1.7) x 10(8) s(-1) range
      and do not vary much between the solvents studied. X-ray diffraction analysis
      shows that the BODIPY core is planar. Molecular dynamics simulations show that
      there is no clear indication for aggregates in solution.

PMID- 19099458
TI  - Optimal alpha-chymotrypsin-catalyzed synthesis of N-Ac-Phe-Gly-NH(2).
AB  - N-Acetyl-phenylalanine-glycinamide (N-Ac-Phe-Gly-NH(2)), a type of dipeptide
      derivative, was synthesized from N-acetyl phenylalanine ethyl ester and
      glycinamide and catalyzed by alpha-chymotrypsin, a protease, in a biphasic
      system. Response surface methodology with a four-factor, five-level central
      composite rotatable design was employed to evaluate the effects of selected
      parameters that included incubation time, reaction temperature, enzyme activity,
      and pH level on the yield of the dipeptide derivative. The results indicated that
      pH significantly affected the yield of N-Ac-Phe-Gly-NH(2). In a ridge max
      analysis, the optimum condition for this synthesis included an incubation time of
      30.9 min, a reaction temperature of 35.8 degrees C, an enzyme activity of 159.2
      U, and a pH of 8.98. The predicted and the actual (experimental) yields were 98.0
      and 95.1%, respectively.

PMID- 19099459
TI  - Mathematical modeling of the development of antioxidant activity in soybeans
      fermented with Aspergillus oryzae and Aspergillus awamori in the solid state.
AB  - The kinetics of the development fungal growth, beta-glucosidase activity, total
      phenolics, and DPPH scavenging in soybeans fermented with Aspergillus oryzae and
      Aspergillus awamori were studied over an 8-day incubation period. Modified
      logistic equations were then used to describe the experimental fermentation
      profiles. In all cases the models were consistent and the parametric estimations
      were statistically significant. The predicted values have high coefficients of
      linear correlation with the experimental results, and the kinetic parameters
      obtained show that A. oryzae grows more rapidly and produces more antioxidant
      activity than A. awamori.

PMID- 19099460
TI  - Molecular screening of wine lactic acid bacteria degrading hydroxycinnamic acids.
AB  - The potential to produce volatile phenols from hydroxycinnamic acids was
      investigated for lactic acid bacteria (LAB) isolated from Spanish grape must and
      wine. A PCR assay was developed for the detection of LAB that potentially produce
      volatile phenols. Synthetic degenerate oligonucleotides for the specific
      detection of the pdc gene encoding a phenolic acid decarboxylase were designed.
      The pdc PCR assay amplifies a 321 bp DNA fragment from phenolic acid
      decarboxylase. The pdc PCR method was applied to 85 strains belonging to the 6
      main wine LAB species. Lactobacillus plantarum, Lactobacillus brevis, and
      Pediococcus pentosaceus strains produce a positive response in the pdc PCR assay,
      whereas Oenococcus oeni, Lactobacillus hilgardii, and Leuconostoc mesenteroides
      strains did not produce the expected PCR product. The production of vinyl and
      ethyl derivatives from hydroxycinnamic acids in culture media was determined by
      high-performance liquid chromatography. A relationship was found between pdc PCR
      amplification and volatile phenol production, so that the LAB strains that gave a
      positive pdc PCR response produce volatile phenols, whereas strains that did not
      produce a PCR amplicon did not produce volatile phenols. The proposed method
      could be useful for a preliminary identification of LAB strains able to produce
      volatile phenols in wine.

PMID- 19099461
TI  - Broad band two-dimensional manipulation of surface plasmons.
AB  - A plasmonic interference pattern can be formed when multiple surface plasmon
      waves overlap coherently. Utilizing a sharp edge coupling mechanism, we
      experimentally demonstrate plasmonic interference patterns that can be designed
      at will by shaping the edges in a metallic film. The patterns can also be
      dynamically tailored by adjusting the wavelength, the polarization, and the
      incident angle of the excitation light beam. Possessing the subdiffraction
      limited feature resolution, this dynamical manipulation method of surface plasmon
      patterns will have profound potentials in nanolithography, particle manipulation,
      and other related fields.

PMID- 19099462
TI  - Probing the intrinsic properties of exfoliated graphene: Raman spectroscopy of
      free-standing monolayers.
AB  - The properties of pristine, free-standing graphene monolayers prepared by
      mechanical exfoliation of graphite are investigated. The graphene monolayers,
      suspended over open trenches, are examined by means of spatially resolved Raman
      spectroscopy of the G-, D-, and 2D-phonon modes. The G-mode phonons exhibit
      reduced energies (1580 cm(-1)) and increased widths (14 cm(-1)) compared to the
      response of graphene monolayers supported on the SiO(2)-covered substrate. From
      analysis of the G-mode Raman spectra, we deduce that the free-standing graphene
      monolayers are essentially undoped, with an upper bound of 2 x 10(11) cm(-2) for
      the residual carrier concentration. On the supported regions, significantly
      higher and spatially inhomogeneous doping is observed. The free-standing graphene
      monolayers show little local disorder, based on the very weak Raman D-mode
      response. The two-phonon 2D mode of the free-standing graphene monolayers is
      downshifted in frequency compared to that of the supported region of the samples
      and exhibits a narrowed, positively skewed line shape.

PMID- 19099463
TI  - Inherently superoleophobic nanocomposite coatings by spray atomization.
AB  - We describe a technique to fabricate, for the first time, superoleophobic
      coatings by spray casting nanoparticle-polymer suspensions. The method involves
      the use of ZnO nanoparticles blended with a waterborne perfluoroacrylic polymer
      emulsion using cosolvents. Acetone is shown to be an effective compatibilizing
      cosolvent to produce self-assembling nanocomposite slurries that form
      hierarchical nanotextured morphology upon curing. Fabricated coating surface
      morphology is investigated with an environmental scanning electron microscope
      (ESEM), and surface wettability is characterized by static and dynamic contact
      angle measurements. The coatings can be applied to large and/or flexible
      substrates by spray coating with ease and require no additional surface
      treatments of commonly used hydrophobic molecules such as fluorosilanes; i.e.,
      the nanocomposites are inherently superoleophobic. The superoleophobic nature of
      the coatings is also discussed within the framework of Cassie-Baxter and Wenzel
      wetting theories.

PMID- 19099464
TI  - Calyciphyllines N-P, alkaloids from Daphniphyllum calycinum.
AB  - Three new Daphniphyllum alkaloids, calyciphyllines N-P (1-3), were isolated from
      the leaves and stems of Daphniphyllum calycinum. The structures and relative
      stereochemistry of 1-3 were elucidated on the basis of spectroscopic data.

PMID- 19099465
TI  - Polyvalent DNA nanoparticle conjugates stabilize nucleic acids.
AB  - Polyvalent oligonucleotide gold nanoparticle conjugates have unique fundamental
      properties including distance-dependent plasmon coupling, enhanced binding
      affinity, and the ability to enter cells and resist enzymatic degradation.
      Stability in the presence of enzymes is a key consideration for therapeutic uses;
      however the manner and mechanism by which such nanoparticles are able to resist
      enzymatic degradation is unknown. Here, we quantify the enhanced stability of
      polyvalent gold oligonucleotide nanoparticle conjugates with respect to enzyme
      catalyzed hydrolysis of DNA and present evidence that the negatively charged
      surfaces of the nanoparticles and resultant high local salt concentrations are
      responsible for enhanced stability.

PMID- 19099468
TI  - Experimental study of the kinetics of the reaction of acetic acid with hydroxyl
      radicals from 255 to 355 K.
AB  - The rate constant of the reaction of OH with acetic acid over the temperature
      range of 255-355 K was determined using our High-Pressure Flow System with laser
      induced fluorescence detection of the OH radicals and FTIR spectrometry for
      acetic acid quantification. The rate constant displays a negative temperature
      dependence and can be described by the Arrhenius expression: k(1)(T) = (5.38 +/-
      0.28) x 10(-14) exp(740 +/- 51/T) cm(3) molecule (-1) s(-1), with k(1) = (6.77 +/
      0.14) x 10(-13) cm(3) molecule (-1) s(-1) at 295 K. The negative temperature
      dependence suggests a pre-reactive complex formation between the OH radicals and
      the acetic acid monomer, and this result is consistent with previous reports. The
      use of FTIR spectrometry allows for separation of the acetic acid monomer and
      dimer in the spectrum and gives a measurement of the acetic acid monomer that is
      independent of the temperature measurement and free of reliance on an equilibrium
      constant expression that can introduce high uncertainty. The highly sensitive
      laser-induced fluorescence for OH detection coupled with the FTIR spectrometry
      result in a rate constant measurement with low uncertainty, and the data set
      presented here in the temperature range of 255-355K serves to bridge existing
      data sets that are obtained either above or below room temperature.

PMID- 19099467
TI  - Computational studies of the photophysics of neutral and zwitterionic amino acids
      in an aqueous environment: tyrosine-(H(2)O)(2) and tryptophan-(H(2)O)(2)
      clusters.
AB  - Tyrosine-(H(2)O)(2) and tryptophan-(H(2)O)(2) clusters have been considered as
      models for the study of the photochemistry of neutral and zwitterionic tyrosine
      and tryptophan in an aqueous environment. It has been found that the detachment
      of neutral NH(3) in the S(1) state of the zwitterionic clusters leads to a low
      lying conical intersection of the S(1) and S(0) energy surfaces. This conical
      intersection can provide the mechanism for efficient radiationless deactivation
      of the excited state back to the ground state or, alternatively, deamination
      (loss of ammonia). These results provide a mechanistic explanation of the
      efficient fluorescence quenching and the high quantum yield of ammonia in the UV
      photolysis of tyrosine and tryptophan in aqueous solution.

PMID- 19099469
TI  - Unusual photophysical properties of substituted carbazoles.
AB  - Photophysical properties of a new class of fluorescent, stable carbazoles (B1-B3,
      G1-G3, and R1-R2) as a function of excitation wavelength in matrixes and solution
      are reported. The emission maxima of B1 and B3 and G1-G3 show red shifts (6-16
      nm) and substantially increased fluorescence quantum yields with a decrease in
      temperature from 25 to -10 degrees C. Considerable edge excitation red shift has
      been observed in B2. The emission of G1 shows both specific and general effects
      of solvent while intermolecular excitation energy transfer occurs from the
      naphthyl to the carbazolyl moiety in G3. Lippert-Mataga plots confirm the
      existence of multiple emitting states in each of these compounds.

PMID- 19099466
TI  - Natural products as tools for neuroscience: discovery and development of novel
      agents to treat drug abuse.
AB  - Much of what we know about the neurosciences is the direct result of studying
      psychoactive natural products. Unfortunately, there are many gaps in our
      understanding of the basic biological processes that contribute to the etiology
      of many CNS disorders. The investigation of psychoactive natural products offers
      an excellent approach to identify novel agents to treat CNS disorders and to find
      new chemical tools to better elucidate their biological mechanisms. This review
      will detail recent progress in a program directed toward investigating
      psychoactive natural products with the goal of treating drug abuse by targeting
      kappa opioid receptors.

PMID- 19099470
TI  - Theoretical calculation of electronic circular dichroism of a
      hexahydroxydiphenoyl-containing flavanone glycoside.
AB  - Time-dependent density functional theory (TDDFT) was employed for theoretical
      calculation of electronic circular dichroism (ECD) of a hexahydroxydiphenoyl
      (HHDP)-containing flavanone glycoside, mattucinol-7-O-[4'',6''-O-(aS)
      hexahydroxydiphenoyl]-beta-d-glucopyranoside (2). It identified the roles of the
      (2S)-flavanone and (aS)-HHDP moieties in generating the ECD spectrum of 2 and
      provided theoretical evidence for the empirical ECD rules applicable to monomeric
      flavanones and HHDP-containing compounds. The experimentally observed high
      amplitude positive Cotton effect (CE) around 240 nm in 2 is derived from the (aS)
      HHDP chromophore, while the low-amplitude negative CE in the 260-300 nm region is
      contributed by both the (aS)-HHDP and (2S)-flavanone moieties. The "linker"
      glucosyl moiety has little effect on the overall ECD. It appears that the
      respective chromophores in 2 contribute additively to the overall ECD, and the
      empirical rules are applicable for configurational assignment. However, if an
      (aR)-HHDP chromophore is present, as shown in mattucinol-7-O-[4'',6''-O-(aR)
      hexahydroxydiphenoyl]-beta-d-glucopyranoside (3), the dominant role of the (aR)
      HHDP and interaction between the (aR)-HHDP and (2S)-flavanone moieties in its
      overall ECD may be confusing when applying the empirical rules to experimental
      ECD interpretation. Thus, theoretical calculation of the ECD that quantifies the
      contributions and interactions of different chromophores is essential for the
      assignment of the absolute configuration of such molecules.

PMID- 19099471
TI  - Single nanowire on a film as an efficient SERS-active platform.
AB  - Fabricating well-defined and highly reproducible platforms for surface-enhanced
      Raman scattering (SERS) is very important in developing practical SERS sensors.
      We report a novel SERS platform composed of a single metallic nanowire (NW) on a
      metallic film. Optical excitation of this novel sandwich nanostructure provides a
      line of SERS hot spots (a SERS hot line) at the gap between the NW and the film.
      This single nanowire on a film (SNOF) architecture can be easily fabricated, and
      the position of hot spots can be conveniently located in situ by using an optical
      microscope during the SERS measurement. We show that high-quality SERS spectra
      from benzenethiol, brilliant cresyl blue, and single-stranded DNA can be obtained
      on a SNOF with reliable reproducibility, good time stability, and excellent
      sensitivity, and thus, SNOFs can potentially be employed as effective SERS
      sensors for label-free biomolecule detection. We also report detailed studies of
      polarization- and material-dependent SERS enhancement of the SNOF structure.

PMID- 19099472
TI  - Traversing the "top-down/bottom-up" divide: molecular-scale lithography of self
      assembled ribbons.
AB  - Use of graphitic (hexabenzocoronene-derived) molecules produces cholesteric
      ribbons which serve as molecular resists in a fluorine plasma. This procedure
      allows the shape of the molecular assemblies to be etched into the underlying
      silicon, validating the concept of "molecular resists".

PMID- 19099473
TI  - Two-electron reduction of a vanadium(V) nitride by CO to release cyanate and open
      a coordination site.
AB  - We report herein that the terminal nitride complex Na[NV(N[t-Bu]Ar)(3)] (Na[1
      VN], Ar = 3,5-Me(2)C(6)H(3)) reacts with CO over the course of 24 h to generate
      V(N[t-Bu]Ar)(3) (1-V) and sodium cyanate in an isolated yield of 77%. The
      reaction products were identified using a combination of NMR and IR spectroscopy,
      and cyanate formation was further confirmed by performing a (13)C labeling
      experiment. In addition, we report on the synthesis and structural
      characterization of the isocyanate complex (OCN)V(N[t-Bu]Ar)(3) (1-V(NCO)) to
      compare its redox chemistry with that of (OCN)Nb(N[t-Bu]Ar)(3) (1-Nb(NCO)).
      Electrochemical studies of 1-Nb(NCO) and 1-V(NCO) revealed large differences in
      the M(5+)/M(4+) and M(4+)/M(3+) reduction potentials. Complex 1-V(NCO) displays
      two redox events in the cyclic voltammogram: a quasireversible event -0.11 V vs
      Fc/Fc(+) and a reversible event at -1.56 V vs Fc/Fc(+). Complex 1-Nb(NCO)
      displays two redox events as well: a quasireversible event at -1.1 V and an
      irreversible event at -2.9 V vs Fc/Fc(+).

PMID- 19099475
TI  - Ruthenium-catalyzed cross-coupling of tertiary propargyl alcohols with omega
      alkynenitriles: a regio- and stereoselective surrogate for an aldol condensation.
AB  - A novel catalytic alkyne cross-coupling reaction is reported which connects
      tertiary propargyl alcohols with omega-alkynylnitriles with perfect atom economy.
      This remarkable process generates highly functionalized, stereodefined dienones
      that are formal aldol products in a single step. Moreover, the specificity of the
      cyano substituent for this reaction demonstrates the unique and somewhat
      underappreciated properties of that functional group.

PMID- 19099474
TI  - C-H bond functionalization via hydride transfer: Lewis acid catalyzed alkylation
      reactions by direct intramolecular coupling of sp3 C-H bonds and reactive alkenyl
      oxocarbenium intermediates.
AB  - C-H bond functionalization enables strategically new approaches to the synthesis
      of complex organic molecules including biologically active compounds, research
      probes and functional organic materials. To address the shortcomings of
      transition metal catalyzed processes, we have developed a new approach to direct
      coupling of sp(3) C-H bonds and alkenes based on Lewis acid-promoted hydride
      transfer. Activation of alpha,beta-unsaturated aldehydes and ketones with Lewis
      acid triggers intramolecular hydride transfer, leading to a zwitterionic
      intermediate, which in turn undergoes ionic cyclization to afford the cyclic
      alkylation product. The scope of this method is expanded by the generation of
      alkenyl-oxocarbenium species as highly activated alkene intermediates capable of
      abstracting a hydride from unreactive carbon centers, including benzyl-, allyl-,
      and crotyl-ethers, as well as primary alkyl ethers, at room temperature. The
      alkenyl acetal and ketal substrates show dramatically faster rates of
      cyclization, as well as improved chemical yield and diastereoselectivity,
      compared to the corresponding carbonyl compounds. Furthermore, the use of boron
      trifluoride etherate as the Lewis acid and ethylene glycol as the organocatalyst
      provides a highly active catalytic system, presumably via the in situ formation
      of alkenyl-oxocarbenium intermediates, which eliminates the need for expensive
      transition metal Lewis acids or the preparation of ketal substrates. This binary
      catalytic system greatly improves the efficiency of the hydride transfer
      initiated alkylation reactions.

PMID- 19099476
TI  - Quantum chemical modeling of zeolite-catalyzed methylation reactions: toward
      chemical accuracy for barriers.
AB  - The methylation of ethene, propene, and t-2-butene by methanol over the acidic
      microporous H-ZSM-5 catalyst has been investigated by a range of computational
      methods. Density functional theory (DFT) with periodic boundary conditions (PBE
      functional) fails to describe the experimentally determined decrease of apparent
      energy barriers with the alkene size due to inadequate description of dispersion
      forces. Adding a damped dispersion term expressed as a parametrized sum over atom
      pair C(6) contributions leads to uniformly underestimated barriers due to self
      interaction errors. A hybrid MP2:DFT scheme is presented that combines MP2 energy
      calculations on a series of cluster models of increasing size with periodic DFT
      calculations, which allows extrapolation to the periodic MP2 limit. Additionally,
      errors caused by the use of finite basis sets, contributions of higher order
      correlation effects, zero-point vibrational energy, and thermal contributions to
      the enthalpy were evaluated and added to the "periodic" MP2 estimate. This
      multistep approach leads to enthalpy barriers at 623 K of 104, 77, and 48 kJ/mol
      for ethene, propene, and t-2-butene, respectively, which deviate from the
      experimentally measured values by 0, +13, and +8 kJ/mol. Hence, enthalpy barriers
      can be calculated with near chemical accuracy, which constitutes significant
      progress in the quantum chemical modeling of reactions in heterogeneous catalysis
      in general and microporous zeolites in particular.

PMID- 19099477
TI  - Synthesis and spectroscopic identification of a mu-1,2-disulfidodinickel complex.
AB  - Reduction of elemental sulfur by a monovalent nickel precursor leads to a trans
      1,2-mu-disulfidodinickel(II) complex assigned based on a combination of advanced
      spectroscopic methods in conjunction with density functional theory calculations.
      The disulfido linkage is characterized by an intense optical S --> Ni charge
      transfer transition at 650 nm, which causes a significant distortion of the
      Ni(2)S(2) core along an isotope-sensitive v(S-S) mode at 474 cm(-1), as
      demonstrated by the resonance Raman excitation profile of this vibrational
      feature.

PMID- 19099478
TI  - Heme-copper assembly mediated reductive coupling of nitrogen monoxide (*NO).
AB  - A iron-dinitrosyl species ((6)L)Fe(NO)(2) (2), generated from nitrogen monoxide
      (*NO) binding to its related iron(II)-mononitrosyl complex ((6)L)Fe(NO) (1),
      efficiently effects reductive coupling of two *NO molecules to release nitrous
      oxide (N(2)O), when Cu(+) ion and 2 equiv acid are added; the heme/Cu product is
      [((6)L)Fe(III)...Cu(II)(D)](3+) (D = H(2)O or MeCN). In a control experiment
      where only ((6)L)Fe(NO)(2) (2) is exposed to 2 equiv acid, no UV-vis change is
      observed; upon warming, *NO((g)) is released and ((6)L)Fe(NO) is reformed. The
      copper ion complex within the (6)L ligand framework is required for the *NO
      coupling chemistry. In a further control experiment Cu(+) ion is added to
      ((6)L)Fe(NO)(2) without acid present, [((6)L)Fe(NO)...Cu(II)(NO(2)(-))](+) is
      obtained, with the amount of N(2)O((g)) released fitting with copper(I) ion
      promoted disproportionation chemistry, 3*NO + ligand-Cu(I) --> N(2)O + ligand
      Cu(II)(NO(2)(-)). The chemical system described represents a (stoichiometric)
      functional model for heme/Cu protein nitric oxide reductase activity.

PMID- 19099480
TI  - Synthesis of uniform ferrimagnetic magnetite nanocubes.
AB  - We synthesized uniform ferrimagnetic magnetite nanocubes in the size range from
      20 to 160 nm. The magnetic property of the nanocubes was characterized, and
      magnetic separation of the histidine-tagged protein was demonstrated.

PMID- 19099479
TI  - Rhodium-catalyzed direct oxidative carbonylation of aromatic C-H bond with CO and
      alcohols.
AB  - A general protocol for the rhodium-catalyzed oxidative carbonylation of arenes to
      form esters has been developed. A broad substrate scope has been demonstrated
      allowing carbonylation of electron-rich, electron-poor, and heterocyclic arenes,
      and the reaction shows wide functional group tolerance and excellent
      regioselectivities. Up to 96% yield of ortho-substituted aryl or heteroaryl
      carboxylic esters were obtained with this methodology. The possible mechanism for
      the rhodium-catalyzed oxidative carbonylation reaction was proposed in this
      article. Studies show that Oxone play an important role in the transformation.

PMID- 19099481
TI  - Total synthesis of brevetoxin A.
AB  - A total synthesis of brevetoxin A is reported. Two tetracyclic coupling partners,
      prepared from previously reported advanced fragments, were effectively united via
      a Horner-Wittig olefination. The resulting octacycle was progressed to substrates
      that were explored for reductive etherification, the success of which led to a
      penultimate tetraol intermediate. The tetraol was converted to the natural
      product through an expeditious selective oxidative process followed by
      methylenation.

PMID- 19099482
TI  - Functional IL-10 gene polymorphism is associated with Chagas disease
      cardiomyopathy.
AB  - This study was designed to determine whether the functional IL-10 gene
      polymorphism -1082G/A is associated with the development of cardiomyopathy in
      individuals infected with Trypanosoma cruzi and whether interleukin (IL)-10
      expression can be correlated with patients' cardiac function. Our results
      demonstrated that the polymorphic allele, which correlates with lower expression
      of IL-10, was associated with the development of Chagas disease cardiomyopathy.
      Accordingly, correlative analysis showed that low IL-10 expression was associated
      with worse cardiac function, as determined by left-ventricular ejection fraction
      values. Therefore, the IL-10 gene polymorphism and IL-10 expression are important
      in determining susceptibility to chagasic cardiomyopathy.

PMID- 19099483
TI  - Epidemiology and genotype analysis of sapovirus associated with gastroenteritis
      outbreaks in Alberta, Canada: 2004-2007.
AB  - This study describes the epidemiology and circulating strains of sapovirus
      associated with gastroenteritis outbreaks in Alberta, Canada, from 2004 to 2007.
      Sapovirus was an important cause of gastroenteritis outbreaks, accounting for 43
      (17.6%) of 244 outbreaks in which all samples tested were negative for norovirus.
      All 4 human sapovirus genotypes, GI, GII, GIV, and GV, were found in samples
      during these outbreaks. The greatest amount of sapovirus-associated outbreak
      activity occurred in 2007, after the emergence of genotype GIV in December 2006.
      The majority of sapovirus-associated outbreaks in Alberta during this period (27
      [62.8%] of 43) occurred in hospitals, community long-term care facilities, and
      senior lodges. Adults>65 years of age were the age group most commonly affected.

PMID- 19099485
TI  - New strain of human T lymphotropic virus (HTLV) type 3 in a Pygmy from Cameroon
      with peculiar HTLV serologic results.
AB  - A search for human T lymphotropic virus (HTLV) types 1 and 2 and related viruses
      was performed by serological and molecular means on samples obtained from 421
      adult villagers from the southern Cameroon forest areas. One individual (a 56
      year-old Baka Pygmy hunter) was found to be HTLV-3 infected; however, there was a
      low proviral load in blood cells. Complete sequence analysis of this virus (HTLV
      3Lobak18) indicated a close relationship to human HTLV-3Pyl43 and simian STLV
      3CTO604 strains. Plasma samples from Lobak18, the HTLV-3 infected individual,
      exhibited a peculiar "HTLV-2-like" pattern on Western blot analysis and were
      serologically untypeable by line immunoassay. These results were different from
      those for the 2 previously reported HTLV-3 strains, raising questions about
      serological confirmation of infection with such retroviruses.

PMID- 19099484
TI  - A short course of antibiotic treatment is effective in preventing death from
      experimental inhalational anthrax after discontinuing antibiotics.
AB  - BACKGROUND: Postexposure prophylaxis of inhalational anthrax requires prolonged
      antibiotic therapy or antibiotics and vaccination. The duration of treatment for
      established anthrax is controversial, because retained spores may germinate and
      cause disease after antibiotics are discontinued. Using rhesus macaques, we
      determined whether a short course of antibiotic treatment, as opposed to
      prophylaxis, could effectively treat inhalational anthrax and prevent disease
      caused by the germination of spores after discontinuation of antibiotics.
      METHODS: Two groups of 10 rhesus macaques were exposed to an aerosol dose of
      Bacillus anthracis spores. Animals in group 1 received ciprofloxacin prophylaxis
      beginning 1-2 h after exposure. Those in group 2 began receiving ciprofloxacin
      after becoming bacteremic, and treatment was continued for 10 days. When each
      group 2 animal completed 10 days of therapy, the prophylactic antibiotic was
      discontinued in the paired group 1 animal. RESULTS: In group 1 (prophylaxis), no
      deaths occurred during antibiotic treatment, but only 2 (20%) of 10 animals
      survived after antibiotics were discontinued. In contrast, in group 2
      (treatment), 3 deaths occurred during antibiotic treatment, but all 7 animals
      (100%) alive after 10 days of therapy survived when antibiotics were
      discontinued. CONCLUSIONS: In the treatment of inhalational anthrax, the
      prolonged course of antibiotics required to achieve prophylaxis may not be
      necessary to prevent anthrax that results from the germination of retained spores
      after the discontinuation of antibiotics.

PMID- 19099486
TI  - Helicobacter pylori vacuolating cytotoxin inhibits duodenal bicarbonate secretion
      by a histamine-dependent mechanism in mice.
AB  - BACKGROUND: The pathogenic mechanisms involved in Helicobacter pylori-induced
      duodenal mucosal injury are incompletely understood. In the present study, we
      sought to investigate the effect of H. pylori vacuolating cytotoxin (VacA) on
      duodenal mucosal bicarbonate (HCO3-) secretion. METHODS: Concentrated bacterial
      culture supernatants from an H. pylori wild-type strain producing VacA with s1/m1
      genotypes (P12) and from an isogenic mutant lacking VacA (P12DeltavacA) were
      used. HCO3- secretion by murine duodenal mucosa was examined in vitro in Ussing
      chambers. Duodenal mucosal histamine release was measured using enzyme-linked
      immunosorbent assay. The expression of histamine H2 receptor was examined by
      immunohistochemical analysis. RESULTS: In a dose-dependent manner, the VacA
      positive supernatant P12 reduced prostaglandin E2 (PGE2)-stimulated duodenal
      mucosal HCO3- secretion to a maximum of 49% (P<.0001), whereas P12DeltavacA did
      not result in significant inhibition (P>.05). Purified VacA had a similar effect.
      Histamine H2 receptor antagonists attenuated the effect of P12 on PGE2-induced
      HCO3- secretion. P12 stimulated duodenal histamine release in a dose-dependent
      manner, and exogenous histamine inhibited PGE2-stimulated duodenal HCO3-
      secretion. H2 receptor expression was found in duodenal epithelial cells, the
      enteric nerve plexus, and lymphocytes in Peyer's patch. CONCLUSIONS: H. pylori
      VacA inhibits PGE2-stimulated duodenal epithelial HCO3- secretion by a histamine
      dependent mechanism. This effect likely contributes to the damaging effect of H.
      pylori in the duodenal mucosa.

PMID- 19099488
TI  - Investigation of intrarenal viral infections in kidney transplant recipients
      unveils an association between parvovirus B19 and chronic allograft injury.
AB  - BACKGROUND: The relevance of viral infections in the development of allograft
      lesions is still unclear, although some viruses have been implicated. The present
      study investigated systemic and intrarenal viral infections in kidney transplant
      recipients and their association with the risk of acute rejection and chronic
      allograft injuries that are predictive of long-term dysfunction. METHODS: The
      presence of DNA sequences of human herpesviruses, polyomaviruses, and parvovirus
      B19 was analyzed in renal allograft biopsy specimens obtained at baseline, after
      acute renal dysfunction, and during follow-up evaluation in 69 transplant
      recipients who were children or young adults. Results were correlated with
      clinical data, viral DNAemia, and results of renal function tests and allograft
      histology analyzed at the same time points. RESULTS: Overall, viral DNA was
      detectable in 46% of baseline and 70% of follow-up biopsy specimens of kidney
      allografts, where it generally persisted. The most frequently detected viruses
      were B19 and human herpesvirus 6, already present in donor kidneys, and BK virus
      and Epstein-Barr virus, usually involving the allograft during follow-up. Among
      viruses, only the intrarenal persistence of B19 DNA and B19 DNAemia was
      associated with the development of chronic allograft injury, whereas human
      cytomegalovirus DNAemia was a risk factor for acute rejection. CONCLUSIONS:
      Parvovirus B19 seems to target the kidney electively. Its intrarenal persistence
      is associated with chronic kidney allograft injury.

PMID- 19099487
TI  - Mucosal immunization with attenuated Salmonella enterica serovar Typhi expressing
      protective antigen of anthrax toxin (PA83) primes monkeys for accelerated serum
      antibody responses to parenteral PA83 vaccine.
AB  - Salmonella enterica serovar Typhi vaccine strain CVD 908-htrA was genetically
      engineered for stable plasmid-based expression of protective antigen of anthrax
      toxin (PA83) fused with the export protein ClyA (ClyA-PA83). The priming
      potential of CVD 908-htrA expressing ClyA-PA83 was assessed in 12 rhesus and 20
      cynomolgus macaques that were immunized mucosally (i.e., intranasally) on days 0
      and 14. A parenteral booster with purified PA83 plus alum was given to rhesus
      macaques on days 42 and 225; cynomolgus monkeys received a booster with either PA
      or licensed anthrax vaccine (BioThrax; Emergent Biosolutions) only one time, 3
      months after priming. Monkeys primed with S. Typhi expressing ClyA-PA83 developed
      high levels of serum toxin-neutralization activity (TNA) antibodies (50%
      effective dose [ED50], >1.3x10(3)), 7 days after receipt of the booster, whereas
      unprimed controls lacked serum TNA (ED50, 0). In nonhuman primates, the success
      of this anthrax vaccine strategy based on heterologous mucosal priming followed
      by a parenteral subunit vaccine booster paves the way for clinical trials.

PMID- 19099489
TI  - Increase in the prevalence of the newly discovered pneumococcal serotype 6C in
      the nasopharynx after introduction of pneumococcal conjugate vaccine.
AB  - BACKGROUND: Because pneumococcal serotype 6C was previously not distinguished
      from serotype 6A, the impact of the 7-valent pneumococcal conjugate vaccine
      (PCV7) on the carriage of serotype 6C is unknown. METHODS: The nasopharyngeal
      (NP) prevalence of the 6C serotype was determined using 1326 pneumococcal
      isolates collected from 7 cohorts of Massachusetts children between 1994 and
      2007. Initially, the isolates were serotyped using the quellung reaction;
      subsequently, stored specimens of all putative 6A isolates were tested for 6C
      using monoclonal antibodies. The opsonophagocytic and antibiotic susceptibilities
      of the isolates were determined. RESULTS: The prevalence of 6A was 9.6% (33/343)
      before 2001, 8.0% (18/226) in 2004, and 2.9% (12/416) in 2007. In contrast, the
      prevalence of 6C was 0.6% (2/343) before 2001, 2.2% (5/226) in 2004, and 8.7%
      (36/416) in 2007 (P<.001 for 2/343 vs. 36/416). 6C isolates from 2007 were more
      susceptible to antibiotics than were 6A isolates. PCV7 induced a low ability to
      opsonize different isolates of 6C. CONCLUSIONS: Among NP isolates, the prevalence
      of 6C isolates has increased and the prevalence of 6A isolates has decreased
      since the introduction of PCV7 in Massachusetts in 2000. The observed increase in
      serotype 6C prevalence may be explained by the induction by PCV7 of low amounts
      of functional anti-6C antibody, compared with anti-6A and anti-6B antibodies.

PMID- 19099490
TI  - ortho-Lithiophenyl isocyanide: a versatile precursor for 3H-quinazolin-4-ones and
      3H-quinazolin-4-thiones.
AB  - ortho-Lithiophenyl isocyanide has been generated from ortho-bromophenyl
      isocyanide and successfully employed toward the synthesis of 2-substituted phenyl
      isocyanides as well as 2,3-disubstituted 3H-quinazoline-4-ones and 3H-quinazolin
      4-thiones.

PMID- 19099491
TI  - "Singapore Green": a new fluorescent dye for microarray and bioimaging
      applications.
AB  - We have synthesized Singapore Green (SG), a structural hybrid of Tokyo Green and
      Rhodamine 110. This new dye is a green light-emitting substitute for 7
      aminocoumarin, a blue fluorescent dye widely used in enzymatic assays. SG
      conjugated peptide substrates were successfully synthesized and used in
      microarray-based protease substrate profiling and live-cell imaging experiments.

PMID- 19099492
TI  - Palladium-catalyzed cross coupling reaction of benzyl bromides with diazoesters
      for stereoselective synthesis of (E)-alpha,beta-diarylacrylates.
AB  - A Pd-catalyzed cross-coupling reaction of benzyl bromides with alpha
      aryldiazoesters is described, and E-alpha,beta-diarylacrylates were obtained in
      good yields and excellent E-to-Z selectivity (>20:1).

PMID- 19099493
TI  - Site-specifically biotinylated VEGF(121) for near-infrared fluorescence imaging
      of tumor angiogenesis.
AB  - The vascular endothelial growth factor (VEGF)/VEGF receptor (VEGFR) pathway is
      considered to be one of the most important regulators of angiogenesis and a key
      target in anticancer treatment. Imaging VEGFR expression can serve as a new
      paradigm for assessing the efficacy of antiangiogenic cancer therapy, improving
      cancer management, and elucidating the role and modulation of VEGF/VEGFR
      signaling during cancer development and intervention. In this study we developed
      an Avi-tagged VEGF(121) protein, which is site-specifically biotinylated in the
      presence of bacterial BirA biotin ligase. BirA biotinylated VEGF(121)-Avi
      (VEGF(121)-Avib) forms a stable complex with streptavidin-IRDye800 (SA800) that
      retains high affinity for VEGFR in vitro and allows receptor specific targeting
      in vivo in a 67NR murine xenograft model. In contrast, chemical coupling of
      IRDye800 abrogated the VEGFR binding ability of the modified protein both in
      vitro and in vivo. The VEGF(121)-Avib/SA800 complex (VEGF-Avib/SA800) may be used
      for quantitative and repetitive near-infrared fluorescence imaging of VEGFR
      expression and translated into clinic for evaluating cancer and other
      angiogenesis related diseases.

PMID- 19099495
TI  - Palladium-indolylphosphine-catalyzed Hiyama cross-coupling of aryl mesylates.
AB  - Aryl mesylates are found to be applicable as electrophiles in organosilicon
      mediated coupling reactions. The catalyst system comprising 2 mol % of Pd(OAc)(2)
      and CM-phos supporting ligand is highly effective in catalyzing Hiyama cross
      coupling of various aryl and heteroaryl mesylates. Interesting acid additive
      effects show that the presence of 0.25-0.50 equiv of acetic acid efficiently
      suppresses the mesylate decomposition and generally promotes the coupling product
      yields.

PMID- 19099494
TI  - Effects of polymer additives on the crystallization of hydrates: a molecular
      level modulation.
AB  - The purpose of this study is to elucidate the effects of polymer additives on the
      growth behavior and final internal structure of hydrate crystals. The polymers
      used were poly(ethylene) glycol (PEG), ethyl(hydroxyethyl) cellulose (EHEC) and
      hydroxylpropyl methylcellulose (HPMC). Rheological characterization of the
      polymer solutions was carried out. Nitrofurantoin and carbamazepine were
      crystallized separately from a mixture of acetone and polymer/water solution
      through evaporative crystallization. The crystallization process and final
      crystals were characterized by light microscopy, XRPD and FT-IR spectroscopy. PEG
      showed a minor viscosity increase, but polymer network associations were found in
      the EHEC and HPMC solutions. With no additive, nitrofurantoin crystallized as a
      mixture of plate-like (monohydrate I) and needle-like (monohydrate II) crystals.
      All polymers affected the crystalline phase, and HPMC and EHEC also changed the
      crystal morphology from needle-like to dendrite-like. H-Bonding was found to
      exist between these polymers (O-H group) and nitrofurantoin monohydrate (CO==
      group), while this was not the case with carbamazepine hydrate. Additives were
      able to modify the crystal phase and morphology due to H-bonding and polymer
      network properties. We envisage that the improved understanding of additives'
      role provided by this study can be utilized when designing control strategies for
      the crystallization process.

PMID- 19099496
TI  - Catalytic asymmetric synthesis of an HIV integrase inhibitor.
AB  - An efficient synthesis of HIV integrase inhibitor (S)-(-)-1 via a unique
      asymmetric hydrogenation of a mixture of imines/enamine 5a-5b/5c is described.
      Hydrogenation of the imines/enamine by a Rh(I)-Josiphos complex afforded 6 in 90%
      yield and 90% ee. Amide formation completed the synthesis of 1 in 58% overall
      yield from 2, which is readily available from 3,4-dihydro-2H-pyran in a seven
      step sequence. A deuterium labeling study suggests the asymmetric hydrogenation
      proceeds predominantly via the enamine tautomer.

PMID- 19099497
TI  - A molecular cage-based [2]rotaxane that behaves as a molecular muscle.
AB  - We report a molecular cage-based [2]rotaxane that functions as an artificial
      molecular muscle through the control of the addition and removal of fluoride
      anions. The percentage change in molecular length of the [2]rotaxane is about 36%
      between the stretched and contracted states, which is larger than the percentage
      change (approximately 27%) in human muscle.

PMID- 19099498
TI  - Single-step azide introduction in proteins via an aqueous diazo transfer.
AB  - The controlled introduction of azides in proteins provides targetable handles for
      selective protein manipulation. We present here an efficient diazo transfer
      protocol that can be applied in an aqueous solution, leading to the facile
      introduction of azides in the side chains of lysine residues and at the N
      terminus of enzymes, e.g. horseradish peroxidase (HRP) and the red fluorescent
      protein DsRed. The effective introduction of azides was verified by mass
      spectrometry, after which the azido-proteins were used in Cu(I)-catalyzed [3 + 2]
      cycloaddition reactions. Azido-HRP retained its catalytic activity after
      conjugation of a small molecule. This modified protein could also be successfully
      immobilized on the surface of an acetylene-covered polymersome. Azido-DsRed was
      coupled to an acetylene-bearing protein allowing it to act as a fluorescent
      label, demonstrating the wide applicability of the diazo transfer procedure.

PMID- 19099499
TI  - Targeting the urokinase plasminogen activator receptor with synthetic self
      assembly nanoparticles.
AB  - Targeting specific receptors is attracting growing interest in the fields of drug
      delivery and gene therapy for cancer treatment. The urokinase plasminogen
      activator receptor (uPAR) is overexpressed on many tumors,particularly that of
      prostate and breast cancers. The aim of this study is to design, prepare, and
      characterize a synthetic self-assembled nanoparticle that presents targeting
      ligands at a certain conformation and molar ratio onthe surface of the particles.
      Here, we describe the synthesis of a novel uPAR targeting ligand consisting of an
      11-amino-acid sequence named U11 peptide modified with an alkyl chain to form an
      U11 peptide-lipid amphiphile.This peptide-lipid is inserted into the outer layer
      of a parent stealth liposome by post-modification to derive a U11 peptide
      targeted nanoparticle. We demonstrate that the peptide moieties become separated
      into more singular conformations as they are inserted into a liposome membrane,
      rendering them to be sufficiently biologically active to observe specific
      receptor-mediated endocytosis (RME) and delivery of plasmid DNA to uPAR positive
      cells (DU145 cells). The U11 peptide targeted nanoparticle transfection of DU145
      cells is essentially 10-fold higher compared to transfection achieved by
      nanoparticles having a scrambled peptide sequence on their surface.U11 peptide
      targeted nanoparticles also proved to be uPAR-specific, as they did not improve
      transfection levels on the uPAR-negative cell line, HEK293.

PMID- 19099500
TI  - Preparation and measurement of combinatorial screen printed libraries for the
      electrochemical analysis of liquids.
AB  - A combinatorial approach to the development of new screen printing pastes is
      introduced. We used a novel technique for printing electrodes out of different
      binary mixtures of pastes. The pastes applied are based on the transition metals
      iridium and ruthenium in the form of their (IV) oxides. Using multielectrode
      arrays,these pastes were printed on the same substrate in one single step. In
      this work, pH sensors were printed based on a concept using solid state
      electrodes both with the measurement and the reference electrode.After the
      sintering process, the pastes were then evaluated using a robotic setup designed
      to handle the high impedances characteristic for pH sensors as well as to
      automatically manipulate the fluids in contact with the sensors.

PMID- 19099501
TI  - Phase control of graphene nanoribbon by carrier doping: appearance of
      noncollinear magnetism.
AB  - The zigzag graphene nanoribbon (ZGNR) has an antiferromagnetic property, that is,
      the relative spin angle theta between the two edges is 180 degrees . By using
      noncollinear first-principles calculations, we find that the magnetic phase of
      the ZGNR can be controlled by injecting either electrons or holes: as the carrier
      density increases, theta continuously decreases from 180 to 0 degrees , which
      indicates that the net magnetization is possible. Either FET doping or chemical
      doping is found to be possible.

PMID- 19099503
TI  - Glycoproteomics of plasma based on narrow selectivity lectin affinity
      chromatography.
AB  - Lectin affinity chromatography using concanavalin A (Con A), Helix pomatia
      agglutinin (HPA), Lycopersicon esculentum lectin (LEL), Aleuria aurantia lectin
      (AAL) and Lens culinaris agglutinin (LCA) was used to investigate the utility of
      narrow selectivity lectins in the characterization of plasma glycoproteome
      diversity and to recognize cancer associated aberrations in glycosylation.
      Following affinity chromatographic selection, proteins were tryptically digested,
      the peptide fragments separated by reversed phase chromatography (RPC), and
      fractions from RPC identified by tandem mass spectrometry. The diversity of
      glycosylation found with narrow selectivity lectins was generally 2/3 that of Con
      A and not related to protein abundance. Small groups of proteins were found with
      each of the affinity columns, HPA, LEL, AAL, and LCA, that changed 3-fold or more
      in concentration between normal and breast cancer patient plasma. Although the
      number of cancer patients examined was too small to validate cancer marker
      candidates, they are clearly worth examining in a larger, more diverse patient
      population.

PMID- 19099502
TI  - High-throughput liquid-liquid fractionation of multiple protein post
      translational modifications.
AB  - Post-translational protein modifications have contributed significantly to the
      identification of macromolecular biomarkers of biological processes. We have
      modified a two-dimensional HPLC system (Beckman Coulter PF2D ProteomeLab) to
      create proteome maps of post-translational protein modifications. This system
      resolves complex protein mixtures by anion exchange chromatofocusing in the first
      dimension and hydrophobicity (reverse phase chromatography) in the second
      dimension. The simultaneous identification of multiple protein modifications,
      accomplished by incorporating a photo diode array (PDA) detector into the PF2D
      system, facilitates the simultaneous production of three-dimensional proteome
      maps and visualization of both unmodified and post-translationally modified (PTM)
      proteins at their signature wavelengths within the proteome. We describe
      procedures for the simultaneous resolution of proteome maps, the identification
      of proteins modified by nitration, carbonylation, and phosphorylation, and
      proteins with unique spectra such as the heme containing proteins.

PMID- 19099504
TI  - Reorganization energies of diprotonated and saddle-distorted porphyrins in
      photoinduced electron-transfer reduction controlled by conformational distortion.
AB  - Kinetics of photoinduced electron transfer from a series of electron donors to
      the triplet excited states of a series of nonplanar porphyrins, hydrochloride
      salts of saddle-distorted dodecaphenylporphyrin ([H(4)DPP]Cl(2)), tetrakis(2,4,6
      trimethylphyenyl)porphyrin ([H(4)TMP]Cl(2)), tetraphenylporphyrin
      ([H(4)TPP]Cl(2)), and octaphenylporphyrin ([H(4)OPP]Cl(2)), were investigated in
      comparison with those of a planar porphyrin, zinc
      [tetrakis(pentafluorophenyl)]porphyrin [Zn(F(20)TPP)(CH(3)CN)], in deaerated
      acetonitrile by laser flash photolysis. The resulting data were evaluated in
      light of the Marcus theory of electron transfer, allowing us to determine
      reorganization energies of electron transfer to be 1.21 eV for [H(4)TMP]Cl(2),
      1.29 eV for [H(4)TPP]Cl(2), 1.45 eV for [H(4)OPP]Cl(2), 1.69 eV for
      [H(4)DPP]Cl(2), and 0.84 eV for [Zn(F(20)TPP)(CH(3)CN)]. The reorganization
      energies exhibited a linear correlation relative to the out-of-plane
      displacements, which represent the degree of nonplanarity. The rate of electron
      transfer reduction of diprotonated porphyrins is significantly slowed down by
      conformational distortions of the porphyrin ring. This indicates that the
      reorganization energy of electron transfer is governed by structural change,
      giving a larger contribution of inner-sphere bond reorganization energy rather
      than outer-sphere solvent reorganization energy.

PMID- 19099505
TI  - Dissociation profile of protonated fucosyl glycopeptides and quantitation of
      fucosylation levels of glycoproteins by mass spectrometry.
AB  - Mass spectrometry of glycopeptides is an efficient strategy for profiling glycans
      at specific sites in glycoproteins. To assess the reliability of this method for
      determining the fucosylation levels of glycoproteins, we conducted mass
      spectrometry of fucosylated glycopeptides from transferrin and haptoglobin. The
      biantennary glycans containing antenna alpha1,3/4 fucose or alpha1,6 core fucose
      showed different fragmentation behaviors in collision-induced dissociation of
      protonated glycopeptides. Stability was dependent on peptide backbone sequences.
      The major dissociation, cleavage of the GlcNAcbeta1-->2Man linkage of antenna,
      was evident at a slightly lower activation energy for the core fucosylated
      species, while the linkage of alpha1,6 core fucose was more stable than that of
      antenna alpha1,3/4 fucose. However, these fragmentations were induced only with
      sufficient loading of activation energy. The quantitation of fucosylated glycans
      by mass spectrometry of glycopeptides, without collisional activation, was thus
      justified. The fucosylation levels calculated from the signal intensities in
      electrospray (nanospray) ionization and ultraviolet matrix-assisted laser
      desorption/ionization mass spectra were essentially the same. The mass
      spectrometric profiling of glycopeptides from transferrin of congenital disorders
      of glycosylation (CDG-Ia and CDG-IIc) patients demonstrated that the elevation or
      reduction of fucosylation in pathological conditions can be reliably determined
      by MS of glycopeptides.

PMID- 19099506
TI  - Leaf proteome analysis of transgenic plants expressing antiviral antibodies.
AB  - The expression of exogenous antibodies in plant is an effective strategy to
      confer protection against viral infection or to produce molecules with
      pharmaceutical interest. However, the acceptance of the transgenic technology to
      obtain self-protecting plants depends on the assessment of their substantial
      equivalence compared to non-modified crops with an established history of safe
      use. In fact, the possibility exists that the introduction of transgenes in
      plants may alter expression of endogenous genes and/or normal production of
      metabolites. In this study, we investigated whether the expression in plant of
      recombinant antibodies directed against viral proteins may influence the host
      leaf proteome. Two transgenic plant models, generated by Agrobacterium
      tumefaciens-mediated transformation, were analyzed for this purpose, namely,
      Lycopersicon esculentum cv. MicroTom and Nicotiana benthamiana, expressing
      recombinant antibodies against cucumber mosaic virus and tomato spotted wilt
      virus, respectively. To obtain a significant representation of plant proteomes,
      optimized extraction procedures have been devised for each plant species. The
      proteome repertoire of antibody-expressing and control plants was compared by 2
      DE associated to DIGE technology. Among the 2000 spots detected within the gels,
      about 10 resulted differentially expressed in each transgenic model and were
      identified by MALDI-TOF PMF and muLC-ESI-IT-MS/MS procedures. Protein variations
      were restricted to a limited number of defined differences with an average ratio
      below 2.4. Most of the differentially expressed proteins were related to
      photosynthesis or defense function. The overall results suggest that the
      expression of recombinant antibodies in both systems does not significantly alter
      the leaf proteomic profile, contributing to assess the biosafety of resistant
      plants expressing antiviral antibodies.

PMID- 19099507
TI  - Vincristine-induced overexpression of P-glycoprotein in L1210 cells is associated
      with remodeling of cell surface saccharides.
AB  - Multidrug resistance of murine leukemic cell line L1210/VCR (R), obtained by
      adaptation of parental L1210 cells (S) on vincristine, is associated with
      overexpression of P glycoprotein (P-gp, the ATP-dependent drug efflux pump).
      Previously, we found that cytochemical staining of negatively charged cell
      surface binding sites (probably sialic acid) by ruthenium red (RR) revealed a
      compact layer of RR bound to the external coat of S cells. This is in contrast to
      R cells and L1210/VCR cells cultured in the presence of vincristine during the
      last cultivation prior to the experiment (V cells), where the RR layer was either
      reduced or absent. In the current paper, we observed differences in the
      interactions of S, R and V cells with Concanavalin A (ConA) and tomato lectin
      (lycopersicum esculentum agglutinin, LEA). ConA bound and induced cell damage
      more effectively in S cells than in R or V cells. Both of these effects could be
      prevented by methyl-manopyranose, but not by N-acetylglucosamine. In contrast,
      LEA lectin preferentially bound to R and V cells. While LEA agglutinated cells
      more effectively than ConA, it did not cause cell damage comparable to ConA.
      Binding of LEA to the cell surface could be prevented by chitooligosaccharides.
      Both LEA and ConA failed to identify P-gp in lectin blots. Thus, changes in ConA
      and LEA interactions are not caused by massive expression of P-gp in the plasma
      membrane and the consequent exposure of the inner saccharides to the external
      side of the plasma membrane.Taken together, the above facts suggest that S cells
      differ from R and V cells in the composition of cell surface glycosides not
      directly linked to P-gp.

PMID- 19099508
TI  - A novel computational approach to predict transcription factor DNA binding
      preference.
AB  - Transcription is one of the most important processes in cell in which
      transcription factors translate DNA sequences into RNA sequences. Accurate
      prediction of DNA binding preference of transcription factors is valuable for
      understanding the transcription regulatory mechanism and (1) elucidating
      regulation network. (2-4) Here we predict the DNA binding preference of
      transcription factor based on the protein amino acid composition and
      physicochemical properties, 0/1 encoding system of nucleotide, minimum Redundancy
      Maximum Relevance Feature Selection method, (5) and Nearest Neighbor Algorithm.
      The overall prediction accuracy of Jackknife cross-validation test is 91.1%,
      indicating that this approach is a useful tool to explore the relation between
      transcription factor and its binding sites. Moreover, we find that the secondary
      structure and polarizability of transcriptor contribute mostly in the prediction.
      Especially, a 7-nt motif with AT-rich region of the DNA binding sites discovered
      via our method is also consistent with the statistical analysis from the TRANSFAC
      database. (6).

PMID- 19099509
TI  - Development of a single column method for the separation of lipid- and protein
      derived oligosaccharides.
AB  - Fluorescent labeling of oligosaccharides with anthranilic acid (2-aminobenzoic
      acid; 2AA), or 2-aminobenzamide (2AB) permits the rapid, sensitive analysis of
      structures present in cells and tissues. Normal-phase (NP)/hydrophilic
      interaction chromatography (HILIC) is commonly used to separate fluorophore
      derivatized oligosaccharides. Column elution is expressed as glucose units (GU)
      following calculation of relative retention when compared to an external glucose
      oligomer standard. However, there is significant overlap between sialylated and
      neutral oligosaccharides. Normal-phase anion-exchange (NP-AE) HPLC can separate
      differing classes of oligosaccharides according to the number of charged
      residues, but relative retention times in GU cannot be calculated across the
      entire gradient. We have overcome this difficulty by use of a Dionex AS11 column
      that combines both hydrophilic interaction and anion-exchange chromatographies,
      termed HIAX, which enables the calculation of GU values for oligosaccharides that
      carry sialylated or other negatively charged groups. The same method may also be
      employed for 2AB and other fluorophore-labeled oligosaccharides. Additionally,
      the same HPLC eluants are used for the differing HPLC columns. Therefore,
      analysis of HILIC- or HIAX-separated fluorophore-labeled oligosaccharides can be
      performed using a single HPLC system with a single set of eluents following a
      simple column change.

PMID- 19099510
TI  - Identification of a new G-quadruplex motif in the KRAS promoter and design of
      pyrene-modified G4-decoys with antiproliferative activity in pancreatic cancer
      cells.
AB  - A new quadruplex motif located in the promoter of the human KRAS gene, within a
      nuclease hypersensitive element (NHE), has been characterized. Oligonucleotides
      mimicking this quadruplex are found to compete with a DNA-protein complex between
      NHE and a nuclear extract from pancreatic cancer cells. When modified with (R)-1
      O-[4-1-(1-pyrenylethynyl) phenylmethyl]glycerol insertions (TINA), the quadruplex
      oligonucleotides showed a dramatic increase of the T(m) (deltaT(m) from 22 to 32
      degrees C) and a strong antiproliferative effects in Panc-1 cells.

PMID- 19099511
TI  - Label-free, homogeneous, and fluorescence "turn-on" detection of protease using
      conjugated polyelectrolytes.
AB  - A label-free, homogeneous, and sensitive fluorescence "turn-on" approach is
      designed to rapidly detect protease using serine functionalized polythiophene
      (POWT). The fluorescence of POWT solution containing bovine serum albumin (BSA)
      as substrate is efficiently quenched by Cu2+ ions through coordinate interaction
      with serine moieties. Upon adding trypsin to the solution, the BSA is cleaved
      into amino acid or peptide fragments, which are stronger Cu2+ chelators to form
      more stable complexes with Cu2+ ions. Thus, the Cu2+ ion is displaced from POWT
      and the fluorescence of POWT is recovered. By triggering the "turn-on" signal of
      POWT, it is possible to detect the trypsin in real time. "Turn-on" response as
      readout signal is able to effectively reduce background noise and increase
      detection sensitivity. Because of the simplicity, high sensitivity, and rapid
      response, our new enzyme assay shows great potential for protease detection in
      the future.

PMID- 19099512
TI  - Doping limits of grown in situ doped silicon nanowires using phosphine.
AB  - Structural characterization and electrical measurements of silicon nanowires
      (SiNWs) synthesized by Au catalyzed vapor-liquid-solid growth using silane and
      axially doped in situ with phosphine are reported. We demonstrate that highly n
      doped SiNWs can be grown without structural defects and high selectivity and find
      that addition of the dopant reduces the growth rate by less than 8% irrespective
      of the radius. This indicates that also the dopant incorporation is radius
      independent. On the basis of electrical measurements on individual wires, contact
      resistivities as low as 1.2 x 10(-7) omega cm(-2) were extracted. Resistivity
      measurements reveal a reproducible donor incorporation of up to 1.5 x 1020 cm-3
      using a gas phase ratios of Si/P = 1.5 x 10(-2). Higher dopant gas concentrations
      did not lead to an increase of the doping concentration beyond 1.5 x10(20) cm(
      3).

PMID- 19099513
TI  - Regio- and chemoselective synthesis of fully substituted thiophenes.
AB  - A full functionalization of all four positions of the thiophene ring was
      achieved. Starting from readily available 2,5-dichlorothiophene, successive
      magnesiations of the 3- and 4-positions using TMPMgCl x LiCl furnish, after
      trapping with various electrophiles, 3,4-difunctionalized dichlorothiophenes.
      Subsequent dechlorination and metalation or magnesium insertion into the C-Cl
      bond provides fully functionalized thiophenes in high yields. An application to
      the synthesis of a thiophene analogue of Atorvastatin (Lipitor) is reported.

PMID- 19099514
TI  - Carbon dioxide based nephroscopy: a trick for laparoscopic pyelolithotomy.
AB  - For certain selected cases, laparoscopic pyelolithotomy is a practical and
      effective method to manage renal stone disease. One such case is that of an
      ectopically located pelvic kidney with a large stone burden. Here, we describe
      our technique and provide what we feel is a trick to performing a key part of
      this procedure--flexible nephroscopy while using carbon dioxide gas to "inflate"
      the collecting system.

PMID- 19099515
TI  - Robot-assisted laparoscopic excision and ureteroureterostomy for congenital
      midureteral stricture.
AB  - Congenital ureteral strictures most commonly occur at the proximal and distal
      segments of the ureter. Congenital midureteral stricture is a rare entity that is
      usually detected by prenatal ultrasonography and repaired in infants. We present
      the case and video of a congenital midureteral stricture in a 20-year-old woman
      who presented with a severe episode of pyelonephritis. The congenital midureteral
      stricture was successfully managed with robot-assisted laparoscopic excision and
      ureteroureterostomy.

PMID- 19099516
TI  - Percutaneous nephrolithotomy: primary patients versus patients with history of
      open renal surgery.
AB  - BACKGROUND AND PURPOSE: Percutaneous nephrolithotomy (PCNL) is the management
      choice for stones larger than 2 cm or for staghorn calculi. PCNL in secondary or
      tertiary patients poses some difficulties. In this study, we compared these
      patients with patients who were operated on for the first time. PATIENTS AND
      METHODS: A total of 328 PCNLs were performed between January 2003 and June 2007.
      One hundred and forty-two patients who had undergone open renal surgery in the
      past (126 secondary and 16 tertiary were compared with patients who had no
      previous history of open renal stone surgery. The tract was formed by balloon
      dilators, and in situations where it was necessary, fascial dilators were used.
      The operation was concluded by inserting a 14Ch Malecot nephrostomy tube in all
      cases. The number of tracts, operative time, transfusion rate, hospitalization
      time, and residual stones were recorded. RESULTS: Significant differences are not
      observed when the results are compared with the primary cases in terms of tract
      numbers (multiple tracts: 8.5% v 10.2%), operative time (2.3 v 2.2 hours) (P >
      0.05), transfusion rate (540 v 495 mL) (P > 0.21), hospitalization time (4.4 v
      4.2 days) (P = 0.94), complication rate (1.4% v 3%) (P > 0.05), and residual
      stones (5% v 3%) (P > 0.05). CONCLUSIONS: Although the anatomic positional
      differences of the kidney and fibrosis makes access and the procedure technically
      difficult in secondary or tertiary cases, PCNL can be performed with low
      complication and high success rates if safety rules are followed strictly.
      Difficult access can be overcome either by newly developed high-pressure
      balloons, assistance of fascial dilators, or by mechanical dilators.

PMID- 19099517
TI  - Construct validity of the pig intestine model in the simulation of laparoscopic
      urethrovesical anastomosis: tools for objective evaluation.
AB  - PURPOSE: We examined the construct validity of a porcine-intestine model for
      ultimately performing a laparoscopic urethrovesical anastomosis. MATERIALS AND
      METHODS: Pig intestine was used to create a model for laparoscopic urethrovesical
      anastomosis (L-UVA) performed laparoscopically in the LapTrainer. Twelve subjects
      (residents and medical students) with different levels of experience in
      laparoscopy were divided into three groups depending on their previous level of
      training with the laparoscope and with robot-assisted laparoscopic prostatectomy
      (RALP). Each subject performed a running laparoscopic anastomosis of pig
      intestine in the box trainer. Performance time and volume of leak from the
      anastomosis were recorded. RESULTS: Those in the most experienced group completed
      the anastomosis in an average of 34.30 min. Those in the less experienced group
      averaged 67.13 min, and those in the group with no experience averaged 114.72
      min. The difference between the groups was significant with one-way analysis of
      variance (ANOVA) (P < 0.0001). Those in the most experienced group averaged 2.64
      mL of leakage from the anastomosis; the less experienced subjects averaged 9.98
      mL, and those in the group with no experience averaged 26.38 mL. The difference
      between the groups was significant with one-way ANOVA (P = 0.0005). CONCLUSION:
      Tests of performance time and postoperative leakage accurately reflected the
      subjects' degree of experience, indicating that this model for L-UVA provides an
      experience closely resembling the person's past experience and that the porcine
      intestine provides a valid model for simulating the procedure. Measuring volume
      of leakage from the anastomosis provides an objective measure of the quality of
      the anastomosis.

PMID- 19099518
TI  - A study of febrile versus afebrile patients after percutaneous nephrolithotomy
      regarding bacterial etiologic factors through blood and urine cultures and 16S
      rRNA detection in serum.
AB  - PURPOSE: The aim of this study was to determine the types of bacteria raising
      body temperature after a percutaneous nephrolithotomy (PCNL). MATERIALS AND
      METHODS: We conducted a prospective study of 120 patients who underwent PCNL at
      Labbafinejad Medical Center between March and July 2006. Each patient had proven
      negative urine cultures preoperatively and received prophylactic antibiotics at
      the time of the procedure. Fever was defined as an oral temperature higher than
      37.8 degrees C, and those patients with a body temperature lower than 37.8
      degrees C were designated as the control group. The feverish patients were
      divided into two groups: The first group with a temperature below 38.5 degrees C,
      and the second group with a temperature of 38.5 degrees C or higher. Clinical and
      operative charts were reviewed to detect fever during the hospital stay. Three
      simultaneous laboratory tests, including postoperative urine cultures and blood
      cultures, plus postoperative polymerase chain reaction (PCR) tests were carried
      out to determine the causative agents. RESULTS: There were no significant
      differences between the two groups regarding the PCR results. Also, this study
      demonstrated that positive PCR results (pathogen and nonpathogen species) were
      the same in febrile and afebrile groups. CONCLUSION: Considering our findings, we
      may conclude that the effects of the bacterial etiologies in post-PCNL fever are
      insignificant.

PMID- 19099522
TI  - Adhesion forces and contact angles of water strider legs.
AB  - This study investigated the adhesion (pull-off) force and contact angles of a
      water strider's leg. During hydrostatic experiments, the adhesion force was found
      to be 2 dyn. The image of a cross section of a live leg contacted with a deformed
      water surface provided the contact angle of 168.8 degrees . A numerical scheme
      was proposed to determine the water surface on a groove wall of a seta. The
      results showed that the asperities of a seta are almost wetted, and the fraction
      of the wetted projection area was 0.69. Thus, the contact angle of a seta was
      124.8 degrees .

PMID- 19099523
TI  - Native-like structure of proteins at a planar poly(acrylic acid) brush.
AB  - Applying ATR-FTIR (attenuated total reflection Fourier transform infrared) and
      TIRF (total internal reflection fluorescence) spectroscopy, we have studied the
      secondary structure and aggregation properties of different proteins which are
      adsorbed at a poly(acrylic acid) (PAA) brush that covers a macroscopically large,
      planar surface. The PAA brush has been prepared on the surface of an ATR silicon
      crystal or a quartz plate. The preparation includes the deposition of a thin
      poly(styrene) film by spin-coating and the transfer of the diblock copolymer
      poly(styrene)-poly(acrylic acid) onto the hydrophobic film using the Langmuir
      Schafer technique. It has been found that the proteins hen egg white lysozyme,
      bovine serum albumin, bovine alpha-lactalbumin, and bovine insulin adsorb
      spontaneously at a PAA brush at neutral pD values, albeit to different degrees.
      The secondary structure of the proteins was estimated from a decomposition of the
      amide I'-band in the observed ATR-FTIR spectra. Generally, the fractions of
      secondary structure elements recovered in this way were almost identical to those
      found when the proteins are native in solution. In addition, the tendency of
      insulin to form amyloid fibrils has also been tested when the protein is adsorbed
      at a planar PAA brush. Insulin is known to form amyloid fibrils in solution at
      low pH values and elevated temperatures. The experiments performed in this study
      suggest that a PAA brush does not promote fibril formation of insulin. Rather,
      insulin that is adsorbed at a PAA brush seems to be excluded from fibril
      formation pathways even at pD = 2 and 60 degrees C, where fibril formation of
      insulin is triggered in solution. Overall, the results of this study demonstrate
      that a planar PAA brush may serve as a mild environment for immobilized proteins.

PMID- 19099524
TI  - Freeze-thaw and matrix effects in direct high-density lipoprotein cholesterol
      methods.
AB  - BACKGROUND: There is frequent discussion on the susceptibility of direct high
      density lipoprotein cholesterol (HDL-C) methods to matrix effects. In Vitro
      Diagnostics manufacturers recognize this issue and regularly improve their HDL-C
      reagent formulations in subsequent generations. METHODS: The 3rd generation
      direct HDL-C assay from Roche was investigated for matrix effects in comparison
      to the former generation, a Beckman direct HDL-C method and a conventional
      phosphotungstate (PTA)/Mg(2+) precipitation method. In addition, 235 heparin
      plasma samples were measured freshly and after a freeze-thaw cycle with the Roche
      2nd and 3rd generation direct HDL-C. Biases, outliers, and intraclass correlation
      coefficients (ICCs) were calculated for both experiments. Multivariate analysis
      was used to investigate interference by matrix components. RESULTS: In fresh
      samples, Roche 2nd and 3rd generation HDL-C methods averaged +0.15 mmol/L (95%
      CI: 0.13-0.16) and +0.08 mmol/L (95% CI: 0.07-0.09) higher compared to frozen
      samples. In frozen aliquots, ICCs for Roche 2nd and 3rd generation and Beckman
      direct HDL-C as compared to PTA/MgCl(2) were 0.963, 0.966, and 0.924,
      respectively. Predictors of outliers (defined as having an absolute difference
      >0.21 mmol/L) in comparisons of direct methods to the PTA/MgCl(2) precipitation
      method were high triglyceride and low albumin levels. CONCLUSIONS: The 3rd
      generation direct HDL-C from Roche has become insensitive to most matrix effects,
      bringing along more accurate results in hypoalbuminemic and hypertriglyceridemic
      samples. Surprisingly, Roche direct assays produced significantly higher HDL-C
      levels in fresh samples compared to frozen plasma samples. If confirmed by
      others, the latter finding has implications for patient management and
      necessitates further reagent optimization.

PMID- 19099525
TI  - Causes, consequences, detection, and prevention of identification errors in
      laboratory diagnostics.
AB  - Laboratory diagnostics, a pivotal part of clinical decision making, is no safer
      than other areas of healthcare, with most errors occurring in the manually
      intensive preanalytical process. Patient misidentification errors are potentially
      associated with the worst clinical outcome due to the potential for misdiagnosis
      and inappropriate therapy. While it is misleadingly assumed that identification
      errors occur at a low frequency in clinical laboratories, misidentification of
      general laboratory specimens is around 1% and can produce serious harm to
      patients, when not promptly detected. This article focuses on this challenging
      issue, providing an overview on the prevalence and leading causes of
      identification errors, analyzing the potential adverse consequences, and
      providing tentative guidelines for detection and prevention based on direct
      positive identification, the use of information technology for data entry,
      automated systems for patient identification and specimen labeling, two or more
      identifiers during sample collection and delta check technology to identify
      significant variance of results from historical values. Once misidentification is
      detected, rejection and recollection is the most suitable approach to manage the
      specimen.

PMID- 19099526
TI  - Circulating oxidized low-density lipoprotein: a biomarker of atherosclerosis and
      cardiovascular risk?
AB  - Low-density lipoproteins (LDLs) are susceptible to structural modifications by
      oxidation, particularly the small dense LDL particles. The formation of lipid
      peroxidation derivates, such as thiobarbituric reactive substances, conjugated
      dienes, lipid hydroperoxides, and aldehydes, is associated with changes in
      apolipoprotein conformation and affects the functional properties of LDLs.
      Oxidized LDL (oxLDL) formation in the subendothelial space of the arterial wall
      is a key initiating step in atherosclerosis because it contributes to foam cell
      generation, endothelial dysfunction, and inflammatory processes. In the last
      decade, immunoassays were developed using monoclonal antibodies against oxidation
      dependent epitopes of LDL which made it possible to directly measure oxLDL in the
      circulation. Increased circulating oxLDL concentrations have been related to
      cardiovascular disease in some studies, although not always independently after
      adjustment of classical lipid markers. The Asklepios Study, investigating 2524
      healthy middle-aged subjects, showed that circulating oxLDL is affected by many
      biological and lifestyle factors, as well as (generalized) subclinical
      atherosclerosis.

PMID- 19099527
TI  - A pilot survey of the use and implementation of cardiac markers in acute coronary
      syndrome and heart failure across Europe. The CARdiac MArker Guideline Uptake in
      Europe (CARMAGUE) study.
AB  - BACKGROUND: Guidelines on preferred cardiac marker strategies for investigation
      of patients with acute coronary syndromes (ACS) are available from the laboratory
      medicine and cardiology communities. Therefore, implementation of these
      guidelines into daily clinical practice should be a joint effort of laboratory
      specialists and clinicians. This was investigated in this survey. METHODS: A
      pilot study was performed sponsored by the European Federation of Clinical
      Chemistry and Laboratory Medicine. A link to an online questionnaire was e-mailed
      to 990 laboratories from eight European countries in May 2006. The requested
      information included tests performed, clinical protocol development, and
      reference limits. RESULTS: We obtained a total of 220 responses. Out of these,
      208 responses (95%) were from hospitals that provide 24-h admission of patients.
      The suggested turn-around-time (<60 min) was apparently met by >88% for cardiac
      troponin T/I and for CK-MB mass. The majority of the laboratories derive their
      decision limits from kit inserts provided by the manufacturers. The results
      revealed a worrying fact that external quality assessments are not used in all
      testing. CONCLUSIONS: Our survey demonstrated that cardiac troponin is the
      preferred biomarker for the diagnosis of ACS. Half of the participants had
      written protocols, mostly as a result of collaboration between laboratorians and
      clinicians.

PMID- 19099528
TI  - Thrombin induces broad spectrum proteolysis in human  serum samples.
AB  - BACKGROUND: During clotting, a thrombin cleaves fibrinogen releasing
      fibrinopeptide A (FPA). FPA is easily identified in serum using matrix-assisted
      laser desorption/ionization time-of-flight (MALDI-TOF) mass spectrometry (MS).
      Using MALDI-TOF MS, we observed multiple, progressively shorter fragments of
      serum FPA. Following ambient incubation of serum, variations in the content of
      FPA fragments occur over time. Denaturation of a thrombin by heating the serum
      sample appears to minimize this variation. These observations suggest that
      intrinsic proteolytic and peptidolytic activity is elevated in serum and perhaps
      originates from the coagulation cascade enzymes themselves, especially a
      thrombin. METHODS: Extrinsic addition of a thrombin to a subset (3-30 kDa) of
      plasma proteins was carried out to induce proteolysis and to examine the
      resultant peptides to reveal a thrombin susceptible parent proteins. One of these
      identified proteins, hemopexin, was directly digested by a thrombin and the
      peptides examined to confirm the observations from the initial plasma protein
      digestion. RESULTS: Extrinsic addition of a thrombin to a subset (3-30 kDa) of
      plasma proteins results in wide-spread digestion of proteins unrelated to
      coagulation, revealing a substrate range encompassing more than fibrinogen.
      Direct digestion of one of these proteins, hemopexin, by a thrombin confirms
      these observations. CONCLUSIONS: The resulting peptides indicate broad tolerance
      beyond the consensus R-G cleavage site of fibrinogen; in fact, there appears to
      be no bias for the amino acid following the R/K residue. These data support our
      hypothesis that the enzymatic activities inherent to coagulation, or at least to
      thrombin, contribute to destabilization of the protein and peptide content of
      serum.

PMID- 19099529
TI  - Vitamin D: current status and perspectives.
AB  - The role of vitamin D in maintaining bone health has been known for decades.
      Recently, however, the discovery that many tissues expressed the vitamin D
      receptor and were able to transform the 25-OH vitamin D into its most active
      metabolite, 1,25-(OH)(2) vitamin D, has led to a very promising future for this
      "old" molecule. Indeed, observational studies, and more and more interventional
      studies, are raising the importance of a significant vitamin D supplementation
      for not-only skeletal benefits. Among them, 25-OH vitamin D has been found to
      play an important role in prevention of cancers, auto-immune diseases,
      cardiovascular diseases, diabetes, and infections. Vitamin D deficiency, defined
      as serum 25-OH vitamin D levels <30 ng/mL, is very common in our population. The
      cost/benefit ratio and some recently published studies are clearly now in favor
      of a controlled and efficient vitamin D supplementation in these patients
      presenting a 25-OH vitamin D level <30 ng/mL. More attention should also be
      focused on pregnant and lactating women, as well as children and adolescents.

PMID- 19099530
TI  - Novel mesogenic azobenzene dimer at air-water and air-solid interfaces.
AB  - We have synthesized a novel mesogenic azobenzene molecule and studied its
      monolayer film properties at air-water interface (Langmuir film) and air-solid
      interface (Langmuir-Blodgett film). The material, H-shaped dimer bis[5-(4'-n
      dodecyloxy benzoyloxy)-2-(4''-methylphenylazo)phenyl] adipate (12D1H) exhibits a
      smectic C phase between 51 and 48 degrees C on cooling. Surface manometry studies
      showed the formation of a stable monolayer at the air-water interface. Brewster
      angle microscopy (BAM) showed that liquid domains coexisting with the gas region
      at large area transformed to a uniform liquid phase with increasing surface
      density and finally to a collapsed state. We have carried out atomic force
      microscope (AFM) studies on Langmuir-Blodgett (LB) films transferred onto freshly
      cleaved hydrophilic mica substrate. The AFM images showed domains of height of
      about 3.8 nm, which corresponds to the estimated height of the molecule
      confirming the formation of monomolecular film. On a hydrophobic silicon
      substrate, the LB transfer yields a bilayer film, which dewets to form uniform
      nanodroplets of diameter of about 100 nm and height in the range 10-50 nm. Our
      analysis indicated that the mechanism involved in the formation of nanodroplets
      can be attributed to spinodal dewetting. The 12D1H molecule containing an
      azobenzene group undergoes a trans to cis transformation in the presence of
      ultraviolet light. Our surface manometry studies showed that the monolayer in the
      presence of ultraviolet light was more stable with a collapse pressure three
      times that of the monolayer in the dark.

PMID- 19099533
TI  - Oxygen diffusion in cross-linked, ethanol-swollen poly(vinyl alcohol) gels:
      counter-intuitive results reflect microscopic heterogeneities.
AB  - Oxygen diffusion coefficients have been determined in ethanol-swollen poly(vinyl
      alcohol), PVA, gels using a technique wherein oxygen sorption is optically
      monitored using singlet oxygen phosphorescence. Data were recorded as a function
      of the extent to which the PVA chains are chemically cross-linked using
      glutaraldehyde. Contrary to conventional expectation, the diffusion coefficients
      obtained increase with an increase in the extent of cross-linking. This
      observation is interpreted in terms of a cross-link-dependent increase in the
      microscopic heterogeneity of the polymer wherein dense cross-linked domains
      coexist with more fluid domains. It is expected that, in the latter domains,
      segmental motions of the macromolecule that facilitate oxygen diffusion are more
      readily achieved. This model of cross-link-dependent heterogeneity is supported
      by the results of small-angle X-ray scattering experiments. Among other things,
      the data reported herein provide an informative foundation for studies of small
      molecule diffusion in biological cells, particularly during photoinduced cell
      death where the hydrogel-like nature of the cell can change due to cross-linking
      reactions.

PMID- 19099535
TI  - Modulating colloidal adsorption on a two-dimensional protein crystal.
AB  - The geometric and physicochemical properties of the protein streptavidin make it
      a useful building block in the construction and manipulation of nanoscale
      structures and devices. However, one requirement in exploiting streptavidin for
      "bottom-up" assembly is the capability to modulate protein-nanoparticle
      interactions. This work examines the effects of pH and the biotin-streptavidin
      interaction on the adsorption of colloidal gold onto a two-dimensional
      streptavidin crystal. Particle deposition was carried out below (pH 6), at (pH
      7), and above (pH 8) the protein's isoelectric point with both biotinylated and
      nonbiotinylated nanoparticles. Particle surface coverage depends on deposition
      time and pH, and increases by 1.4-10 times when biotin is incorporated onto the
      particle surface. This coverage is highest for both particle types at pH 6 and
      decreases monotonically with increasing pH. Calculations of interparticle
      potentials based on Derjaguin-Landau-Verwey-Overbeek (DLVO) theory demonstrate
      that this trend in surface coverage is most likely due to alterations in particle
      surface electrostatic interactions and not a result of changes in interparticle
      electrostatic repulsion. Furthermore, post-adsorption alterations in pH
      demonstrate that electrostatically adsorbed particles can be selectively desorbed
      from the surface. Evaluation of the nonspecifically adsorbed fraction of
      biotinylated particles indicates that the receptor-ligand adsorption mechanism
      gives a higher rate of attachment to the substrate than nonspecific,
      electrostatic adsorption. This results in faster adsorption kinetics and higher
      coverages for biotinylated particles relative to the nonbiotinylated case.

PMID- 19099536
TI  - The hydrophobic motif of ROCK2 requires association with the N-terminal extension
      for kinase activity.
AB  - ROCK (Rho-associated coiled-coil kinase) 2 is a member of the AGC kinase family
      that plays an essential role downstream of Rho in actin cytoskeleton assembly and
      contractility. The process of ROCK2 activation is complex and requires
      suppression of an autoinhibitory mechanism that is facilitated by Rho binding.
      ROCK2 harbours a C-terminal extension within the kinase domain that contains a
      hydrophobic cluster of phenylalanine and tyrosine residues surrounding a key
      threonine residue. In growth-factor-stimulated AGC kinases, the hydrophobic motif
      is important for the transition of the kinase from inactive to active complex and
      requires phosphorylation of the conserved serine/threonine residue. Less is
      understood about the contribution that the hydrophobic motif plays in the
      activation of ROCK, and the role of the hydrophobic motif threonine at position
      405. In the present study, we show that this residue of ROCK is essential for
      substrate phosphorylation and kinase domain dimerization. However, in contrast
      with the growth-factor-activated AGC kinases, a phosphomimetic residue at
      position 405 was inhibitory for ROCK2 activity and dimerization. A soluble
      hydrophobic motif peptide allosterically activated ROCK2 In vitro, but not the
      equivalent peptide with Asp(405) substitution. Mechanistically, both ROCK2
      activity and dimerization were dependent upon the interaction between Thr(405) of
      the hydrophobic motif and Asp(39) of the N-terminal extension. The reciprocal
      exchange of these residues was permissive for kinase activity, but dimerization
      was lost. These results support the rationale for development of small-molecule
      inhibitors designed to block ROCK activation by selectively interfering with
      hydrophobic motif-mediated activation-state transition and dimer formation.

PMID- 19099537
TI  - A traffic signal for heterodimeric amino acid transporters to transfer from the
      ER to the Golgi.
AB  - Heterodimeric amino acid transporters represent a unique class of transport
      systems that consist of a light chain that serves as the 'transporter proper' and
      a heavy chain that is necessary for targeting the complex to the plasma membrane.
      The currently prevailing paradigm assigns no role for the light chains in the
      cellular processing of these transporters. In this issue of the Biochemical
      Journal, Sakamoto et al. provide evidence contrary to this paradigm. Their
      studies with the rBAT -b(0,+)AT (related to b(0,+) amino acid transporter-b(0,+)
      type amino acid transporter) heterodimeric amino acid transporter show that the C
      terminus of the light chain b(0,+)AT contains a sequence motif that serves as the
      traffic signal for the transfer of the heterodimeric complex from the endoplasmic
      reticulum to the Golgi. This is a novel function for the light chain in addition
      to its already established role as the subunit responsible for the transport
      activity. These new findings also seem to be applicable to other heterodimeric
      amino acid transporters as well.

PMID- 19099538
TI  - Evolution of protein phosphatases in plants and animals.
AB  - Protein phosphorylation appears to be a universal mechanism of protein
      regulation. Genomics has provided the means to compile inventories of protein
      phosphatases across a wide selection of organisms and this has supplied insights
      into the evolution of this group of enzymes. Protein phosphatases evolved
      independently several times yielding the groups we observe today. Starting from a
      core catalytic domain, phosphatases evolved by a series of gene duplication
      events and by adopting the use of regulatory subunits and/or fusion with novel
      functional modules or domains. Recent analyses also suggest that the
      serine/threonine specific enzymes are more ancient than the PTPs (protein
      tyrosine phosphatases). It is likely that the latter played a key role at the
      onset of metazoan evolution in conjunction with the tremendous expansion of
      tyrosine kinases and PTPs at this point. In the present review, we discuss the
      evolution of the PTPs, the serine/threonine specific PPP (phosphoprotein
      phosphatase) and PPM (metallo-dependent protein phosphatase) families and the
      more recently discovered phosphatases that utilize an aspartate-based catalytic
      mechanism. We will also highlight examples of convergent evolution and several
      phosphatases which are unique to plants.

PMID- 19099539
TI  - The TGF-beta, PI3K/Akt and PTEN pathways: established and proposed biochemical
      integration in prostate cancer.
AB  - A key to the development of improved pharmacological treatment strategies for
      cancer is an understanding of the integration of biochemical pathways involved in
      both tumorigenesis and cancer suppression. Furthermore, genetic markers that may
      predict the outcome of targeted pharmacological intervention in an individual are
      central to patient-focused treatment regimens rather than the traditional 'one
      size fits all' approach. Prostate cancer is a highly heterogeneous disease in
      which a patient-tailored care program is a holy grail. This review will describe
      the evidence that demonstrates the integration of three established pathways: the
      tumour-suppressive TGF-beta (transforming growth factor-beta) pathway, the
      tumorigenic PI3K/Akt (phosphoinositide 3-kinase/protein kinase B) pathway and the
      tumour-suppressive PTEN (phosphatase and tensin homologue deleted on chromosome
      10) pathway. It will discuss gene polymorphisms and somatic mutations in relevant
      genes and highlight novel pharmaceutical agents that target key points in these
      integrated pathways.

PMID- 19099540
TI  - Bicarbonate transport in cell physiology and disease.
AB  - The family of mammalian bicarbonate transport proteins are involved in a wide
      range of physiological processes. The importance of bicarbonate transport follows
      from the biochemistry of HCO(3)(-) itself. Bicarbonate is the waste product of
      mitochondrial respiration. HCO(3)(-) undergoes pH-dependent conversion into CO(2)
      and in doing so converts from a membrane impermeant anion into a gas that can
      diffuse across membranes. The CO(2)-HCO(3)(-) equilibrium forms the most
      important pH buffering system of our bodies. Bicarbonate transport proteins
      facilitate the movement of membrane-impermeant HCO(3)(-) across membranes to
      accelerate disposal of waste CO(2), control cellular and whole-body pH, and to
      regulate fluid movement and acid/base secretion. Defects of bicarbonate transport
      proteins manifest in diseases of most organ systems. Fourteen gene products
      facilitate mammalian bicarbonate transport, whose physiology and pathophysiology
      is discussed in the present review.

PMID- 19099541
TI  - Mapping of a copper-binding site on the small CP12 chloroplastic protein of
      Chlamydomonas reinhardtii using top-down mass spectrometry and site-directed
      mutagenesis.
AB  - CP12 is a small chloroplastic protein involved in the Calvin cycle that was shown
      to bind copper, a metal ion that is involved in the transition of CP12 from a
      reduced to an oxidized state. In order to describe CP12's copper-binding
      properties, copper-IMAC experiments and site-directed mutagenesis based on
      computational modelling, were coupled with top-down MS [electrospray-ionization
      MS and MS/MS (tandem MS)]. Immobilized-copper-ion-affinity-chromatographic
      experiments allowed the primary characterization of the effects of mutation on
      copper binding. Top-down MS/MS experiments carried out under non-denaturing
      conditions on wild-type and mutant CP12-Cu(2+) complexes then allowed fragment
      ions specifically binding the copper ion to be determined. Comparison of MS/MS
      datasets defined three regions involved in metal ion binding: residues Asp(16)
      Asp(23), Asp(38)-Lys(50) and Asp(70)-Glu(76), with the two first regions
      containing selected residues for mutation. These data confirmed that copper
      ligands involved glutamic acid and aspartic residues, a situation that contrasts
      with that obtaining for typical protein copper chelators. We propose that copper
      might play a role in the regulation of the biological activity of CP12.

PMID- 19099542
TI  - Stratum corneum lipid organization as observed by atomic force, confocal and two
      photon excitation fluorescence microscopy.
AB  - Skin moisturization is largely a function of stratum corneum barrier capacity,
      which in turn is a function of the physical state and structural organization of
      the stratum corneum extracellular lipid matrix [J. Invest. Dermatol.18, 433
      (1952); AIChE J. 21, 985 (1975); Acta Derm. Venereol.74, 1 (1994); J. Invest.
      Dermatol.117, 830 (2001)]. Three unsolved key questions with respect to this
      lipid matrix' structural organization [Acta Derm. Venereol.74, 1 (1994); J.
      Invest. Dermatol.117, 830 (2001); J. Invest. Dermatol.118, 897 (2002); J. Invest.
      Dermatol.118, 899 (2002)] are: i) whether the lipid matrix is constituted by a
      single-gel phase or by co-existing solid (crystalline or gel) domains, ii)
      whether a separate fluid (liquid crystalline) phase is present and iii) whether
      the local pH has a direct effect on the lipid matrix' phase behaviour. Using an
      array of complementary visual-related biophysical techniques (e.g. atomic force
      microscopy and confocal/two-photon excitation fluorescence microscopy), it was
      recently shown that reconstituted membranes composed of extracted decontaminated
      human stratum corneum lipids do not form a fluid phase, but exclusively a single
      gel phase that segregates into co-existing microscopic domains below pH 6
      [Biophys. J.93, 3142 (2007)]. It was further shown that the role of cholesterol
      is related to dispersion of ceramide-enriched domains. This effect is
      counteracted by the presence of free fatty acids, which mix with skin ceramides
      but not with cholesterol.

PMID- 19099543
TI  - Location-related differences in structure and function of the stratum corneum
      with special emphasis on those of the facial skin.
AB  - Between the two different kinds of the skin covering the body, the glabrous skin
      is found only on the palmo-plantar surface because of its rather simple function
      to protect the underlying living tissue with its remarkably thick stratum corneum
      (SC) from strong external force and friction. Thus, its barrier function is
      extremely poor. In contrast, the hair-bearing skin covers almost all over the
      body surface regardless of the presence of long hair or vellus hair. In regard to
      its SC, many dermatologists and skin scientists think that it is too thin to show
      any site-specific differences, because the SC is just present as an efficient
      barrier membrane to protect our body from desiccation as well as against the
      invasion by external injurious agents. However, there are remarkable regional
      differences not only in the living skin tissue but also even in such thin SC
      reflecting the function of each anatomical location. These differences in the SC
      have been mostly disclosed with the advent of non-invasive biophysical
      instruments, particularly the one that enables us to measure transepidermal water
      loss (TEWL), the parameter of the SC barrier function, and the one that evaluates
      the hydration state of the skin surface, the parameter of the water-holding
      capacity of the SC that brings about softness and smoothness to the skin surface.
      These in vivo instrumental measurements of the SC have disclosed the presence of
      remarkable differences in the functional properties of the SC particularly
      between the face and other portions of the body. The SC of the facial skin is
      thinner, being composed of smaller layers of corneocytes than that of the trunk
      and limbs. It shows unique functional characteristics to provide hydrated skin
      surface but relatively poor barrier function, which is similar to that observed
      in retinoid-treated skin or to that of fresh scar or keloidal scars. Moreover,
      there even exist unexpected, site-dependent differences in the SC of the facial
      skin such as the forehead, eyelid, cheek, nose and perioral regions, although
      each location occupies only a small area. Between these locations, the cheek
      shows the lowest TEWL in contrast to the perioral region that reveals the highest
      one. Moreover, these features are not static but change with age particularly
      between children and adults and maybe also between genders. Among various facial
      locations, the eyelid skin is distinct from others because its SC is associated
      with poor skin surface lipids and a thin SC cell layer composed of large
      corneocytes that brings about high surface hydration state but poor barrier
      function, whereas the vermillion borders of the lips that are covered by an
      exposed part of the oral mucosa exhibit remarkably poor barrier function and low
      hydration state. Future studies aiming at the establishment of the functional
      mapping in each facial region and in other body regions will shed light on more
      delicate site-dependent differences, which will provide us important information
      in planning the strategy to start so called tailor-made skin care for each
      location of the body.

PMID- 19099544
TI  - Increased basal transepidermal water loss leads to elevation of some but not all
      stratum corneum serine proteases.
AB  - There are indications of elevation of some inflammatory serine proteases in
      barrier damaged skin (e.g. plasmin and urokinase). Moreover, many other serine
      protease activities are present such as desquamatory enzymes as well as a newly
      detected tryptase-like serine protease. However, the activities of these
      proteases have never been correlated with stratum corneum (SC) barrier function.
      The activity of extractable key serine proteases (SC trypsin-like kallikreins, SC
      chymotrypsin-like kallikreins, SC tryptase-like serine protease, urokinase and
      plasmin) was measured from the outermost layers of SC obtained from facial tape
      strippings in clinically normal subjects. The protein content of the tape
      strippings was quantified by absorption measurements with the novel infrared
      densitometer SquameScan 850A and the protease activities by the use of
      fluorogenic peptide substrates. SC barrier function, SC hydration and skin
      surface pH were measured using AquaFlux, NOVA dermal phase meter and Skin-pH
      Meter, respectively. As expected, SC hydration was reduced with increased
      transepidermal water loss (TEWL) values indicative of barrier impairment.
      Surprisingly, SC chymotrypsin-like activity showed no correlation with hydration
      or TEWL, whereas all other enzymes positively correlated with impaired barrier
      function and some were statistically significant: SC trypsin-like kallikreins
      (R(2 )=0.66, P < 0.01), SC tryptase-like enzyme (R(2 )=0.95, P < 0.001), plasmin
      (R(2 )=0.86, P < 0.001) and urokinase (R(2 )=0.50, P < 0.05). All enzymes except
      urokinase also negatively correlated with SC hydration. Elevated levels of SC
      serine proteases have been associated with some dermatological disorders, such as
      atopic dermatitis, psoriasis and rosacea but these results indicate that these
      enzymes are also elevated with milder forms of barrier disruption, which is not
      clinically evident as irritated skin. As these proteases are elevated in the SC,
      they will also be elevated in the epidermis where they can be involved in
      neurogenic inflammation and epidermal barrier impairment via activation of the
      protease-activated receptors. These results highlight the need for using serine
      protease inhibitors especially for urokinase and plasmin, SC tryptase-like serine
      protease and possibly SC trypsin-like kallikreins even in milder forms of barrier
      damage.

PMID- 19099545
TI  - Characterization of cosmetic cream with Mesembryanthemum crystallinum plant
      extract: influence of formulation composition on physical stability and anti
      oxidant activity.
AB  - Cosmetic or pharmaceutical composition containing superoxide dismutase (SOD) was
      usually used in topical administration, particularly, in fighting against skin
      ageing and in the protection of the skin against radiation exposure.
      Mesembryanthemum crystallinum is a halophyte plant widely used in the traditional
      medicine, characterized by the presence of anti-oxidants enzymes in responses to
      abiotic stresses. In the present study, we prepared a formulation with M.
      crystallinum extract characterized by naturally occurring SOD and catalase in
      association with other anti-oxidants molecules. The SOD activity was measured by
      3-(4,5-dimethyldiazol-2-yl)-2,5-diphenyl-tetrazolium bromide/riboflavin method,
      catalase by colorimetric method and the total anti-radical activity was measured
      by 1,1-diphenyl-2-picrylhydrazyl radical (DPPH) method. Formulations contain a
      significant SOD activity (8.33 U mg(-1)), a catalase activity (0.5 x 10(7) UC)
      and an anti-radical activity (30% of DPPH inhibition). The formulation storage
      (15 days at 4 degrees C) showed a marked loss of total anti-oxidant capacity. The
      addition of the M. crystallinum extract induced also a reduction in formulation
      viscosity and pH.

PMID- 19099546
TI  - Stability of vitamin C derivatives in topical formulations containing lipoic
      acid, vitamins A and E.
AB  - The stability of ascorbyl palmitate, sodium ascorbyl phosphate and magnesium
      ascorbyl phosphate in topical formulations was investigated by direct reverse
      phase high performance liquid chromatography after sample dilution with a
      suitable buffer - organic solvent mixture. Ascorbyl palmitate, sodium ascorbyl
      phosphate and magnesium ascorbyl phosphate are derivatives of ascorbic acid which
      differ in hydrolipophilic properties. They are widely used in cosmetic and
      pharmaceutical preparations. According to the results, ascorbyl esters showed
      significant differences: sodium ascorbyl phosphate and magnesium ascorbyl
      phosphate are more stable derivatives of vitamin C than ascorbyl palmitate and
      may be easily used in cosmetic products.

PMID- 19099547
TI  - Chitin-glucan, a natural cell scaffold for skin moisturization and rejuvenation.
AB  - Two clinical studies were conducted to evaluate the tolerance and effects of a
      copolymer of chitin and beta-glucan, forming the exoskeleton of fungal cell
      walls, now supplied for cosmetic applications. A 6-week randomized, double-blind,
      placebo-controlled study was conducted on 13 volunteers with sensitive skin to
      compare with 0.5-2% formulations chitin-glucan applied twice daily.
      Biometrological evaluations showed that erythema did not develop, the water
      retention capacity of the stratum corneum increased and the transepidermal water
      loss moderately decreased. Another 16-week randomized, double-blind, placebo
      controlled study was conducted on 20 men showing signs of ageing skin. A 1.5%
      chitin-glucan formulation was applied twice daily. Objective biometrological
      assessments showed a progressive increase in skin firmness and stratum corneum
      hydration when desquamation and skin roughness decreased. In conclusion, the
      chitin-glucan formulations appear safe. They significantly mitigate some signs of
      skin ageing and improve both stratum corneum hydration and skin barrier function.

PMID- 19099548
TI  - Recalls of microbiologically contaminated cosmetics in EU from 2005 to May 2008.
AB  - The Rapid Alert System for non-food consumer products in the EU (RAPEX) notifies
      each week the member countries on dangerous products sold in the EU.
      Microbiological contaminated cosmetics pose a potential health risk and are
      recalled from the market. This study investigated the number of recalled
      microbiological contaminated cosmetics products in the RAPEX database from 2005
      to until week 17 in 2008. A total of 173 cosmetic products were recalled in the
      period, 24 were contaminated and the most frequently found micro-organism was the
      pathogenic Pseudomonas aeruginosa. It appears that the number of contaminated
      cosmetic products could be two to three times higher in 2008 compared to 2007.
      The recalled products were manufactured in 17 different countries and only one
      company had more than one product recalled. It is important to keep monitoring
      the cosmetic products for contamination because an increasing number of products
      are recalled each year, and the majority is contaminated with potential
      pathogenic micro-organism. More knowledge on the reasons for the contamination is
      needed.

PMID- 19099552
TI  - In vitro effects of nanoparticles on renal cells.
AB  - BACKGROUND: The ability of nanoparticles to cross the lung-blood barrier suggests
      that they may translocate to blood and to targets distant from their portal of
      entry. Nevertheless, nanotoxicity in organs has received little attention. The
      purpose of this study was to evaluate nanotoxicity in renal cells using in vitro
      models. Various carbon black (CB) (FW2-13 nm, Printex60-21 nm and LB101-95 nm)
      and titanium dioxide (TiO2-15 and TiO2-50 nm) nanoparticles were characterized on
      size by electron microscopy. We evaluated theirs effects on glomerular mesangial
      (IP15) and epithelial proximal tubular (LLC-PK1) renal cells, using light
      microscopy, WST-1 assay, immunofluorescence labeling and DCFH-DA for reactive
      oxygen species (ROS) assay. RESULTS: Nanoparticles induced a variety of cell
      responses. On both IP15 and LLC-PK1 cells, the smallest FW2 NP was found to be
      the most cytotoxic with classic dose-behavior. For the other NPs tested,
      different cytotoxic profiles were found, with LLC-PK1 cells being more sensitive
      than IP15 cells. Exposure to FW2 NPs, evidenced in our experiments as the most
      cytotoxic particle type, significantly enhanced production of ROS in both IP15
      and LLC-PK1 cells. Immunofluorescence microscopy using latex beads indicated that
      depending on their size, the cells internalized particles, which accumulated in
      the cell cytoplasm. Additionally using transmission electronic microscope
      micrographs show nanoparticles inside the cells and trapped in vesicles.
      CONCLUSION: The present data constitute the first step towards determining in
      vitro dose effect of manufactured CB and TiO2 NPs in renal cells.
      Cytotoxicological assays using epithelial tubular and glomerular mesangial cell
      lines rapidly provide information and demonstrated that NP materials exhibit
      varying degrees of cytotoxicity. It seems clear that in vitro cellular systems
      will need to be further developed, standardized and validated (relative to in
      vivo effects) in order to provide useful screening data about the relative
      toxicity of nanoparticles.

PMID- 19099551
TI  - The genome sequence of the fish pathogen Aliivibrio salmonicida strain LFI1238
      shows extensive evidence of gene decay.
AB  - BACKGROUND: The fish pathogen Aliivibrio salmonicida is the causative agent of
      cold-water vibriosis in marine aquaculture. The Gram-negative bacterium causes
      tissue degradation, hemolysis and sepsis in vivo. RESULTS: In total, 4 286
      protein coding sequences were identified, and the 4.6 Mb genome of A. salmonicida
      has a six partite architecture with two chromosomes and four plasmids. Sequence
      analysis revealed a highly fragmented genome structure caused by the insertion of
      an extensive number of insertion sequence (IS) elements. The IS elements can be
      related to important evolutionary events such as gene acquisition, gene loss and
      chromosomal rearrangements. New A. salmonicida functional capabilities that may
      have been aquired through horizontal DNA transfer include genes involved in iron
      acquisition, and protein secretion and play potential roles in pathogenicity. On
      the other hand, the degeneration of 370 genes and consequent loss of specific
      functions suggest that A. salmonicida has a reduced metabolic and physiological
      capacity in comparison to related Vibrionaceae species. CONCLUSION: Most
      prominent is the loss of several genes involved in the utilisation of the
      polysaccharide chitin. In particular, the disruption of three extracellular
      chitinases responsible for enzymatic breakdown of chitin makes A. salmonicida
      unable to grow on the polymer form of chitin. These, and other losses could
      restrict the variety of carrier organisms A. salmonicida can attach to, and
      associate with. Gene acquisition and gene loss may be related to the emergence of
      A. salmonicida as a fish pathogen.

PMID- 19099550
TI  - targetTB: a target identification pipeline for Mycobacterium tuberculosis through
      an interactome, reactome and genome-scale structural analysis.
AB  - BACKGROUND: Tuberculosis still remains one of the largest killer infectious
      diseases, warranting the identification of newer targets and drugs.
      Identification and validation of appropriate targets for designing drugs are
      critical steps in drug discovery, which are at present major bottle-necks. A
      majority of drugs in current clinical use for many diseases have been designed
      without the knowledge of the targets, perhaps because standard methodologies to
      identify such targets in a high-throughput fashion do not really exist. With
      different kinds of 'omics' data that are now available, computational approaches
      can be powerful means of obtaining short-lists of possible targets for further
      experimental validation. RESULTS: We report a comprehensive in silico target
      identification pipeline, targetTB, for Mycobacterium tuberculosis. The pipeline
      incorporates a network analysis of the protein-protein interactome, a flux
      balance analysis of the reactome, experimentally derived phenotype essentiality
      data, sequence analyses and a structural assessment of targetability, using novel
      algorithms recently developed by us. Using flux balance analysis and network
      analysis, proteins critical for survival of M. tuberculosis are first identified,
      followed by comparative genomics with the host, finally incorporating a novel
      structural analysis of the binding sites to assess the feasibility of a protein
      as a target. Further analyses include correlation with expression data and non
      similarity to gut flora proteins as well as 'anti-targets' in the host, leading
      to the identification of 451 high-confidence targets. Through phylogenetic
      profiling against 228 pathogen genomes, shortlisted targets have been further
      explored to identify broad-spectrum antibiotic targets, while also identifying
      those specific to tuberculosis. Targets that address mycobacterial persistence
      and drug resistance mechanisms are also analysed. CONCLUSION: The pipeline
      developed provides rational schema for drug target identification that are likely
      to have high rates of success, which is expected to save enormous amounts of
      money, resources and time in the drug discovery process. A thorough comparison
      with previously suggested targets in the literature demonstrates the usefulness
      of the integrated approach used in our study, highlighting the importance of
      systems-level analyses in particular. The method has the potential to be used as
      a general strategy for target identification and validation and hence
      significantly impact most drug discovery programmes.

PMID- 19099553
TI  - Hepatitis A, B and C viral co-infections among HIV-infected adults presenting for
      care and treatment at Muhimbili National Hospital in Dar es Salaam, Tanzania.
AB  - BACKGROUND: Tanzania is currently scaling-up access to anti-retro viral therapy
      (ART) to reach as many eligible persons as possible. Hepatitis viral co
      infections are known to influence progression, management as well as outcome of
      HIV infection. However, information is scarce regarding the prevalence and
      predictors of viral hepatitis co-infection among HIV-infected individuals
      presenting at the HIV care and treatment clinics in the country. METHODS: A cross
      sectional study conducted between April and September 2006 enrolled 260 HIV-1
      infected, HAART naive patients aged > or = 18 years presenting at the HIV care
      and treatment clinic (CTC) of the Muhimbili National Hospital (MNH). The
      evaluation included clinical assessment and determination of CD4+ T-lymphocyte
      count, serum transaminases and serology for Hepatitis A, B and C markers by
      ELISA. RESULTS: The prevalence of anti HAV IgM, HBsAg, anti-HBc IgM and anti-HCV
      IgG antibodies were 3.1%, 17.3%, 2.3% and 18.1%, respectively. Dual co-infection
      with HBV and HCV occurred in 10 individuals (3.9%), while that of HAV and HBV was
      detected in two subjects (0.8%). None of the patients had all the three hepatitis
      viruses. Most patients (81.1%) with hepatitis co-infection neither had specific
      clinical features nor raised serum transaminases. History of blood transfusion
      and jaundice were independent predictors for HBsAg and anti-HBc IgM positivity,
      respectively. CONCLUSION: There is high prevalence of markers for hepatitis B and
      C infections among HIV infected patients seeking care and treatment at MNH.
      Clinical features and a raise in serum alanine aminotransferase were of limited
      predictive values for the viral co-infections. Efforts to scale up HAART should
      also address co-infections with Hepatitis B and C viruses.

PMID- 19099554
TI  - Aberrant expression of ID2 protein and its correlation with EBV-LMP1 and
      P16(INK4A) in classical Hodgkin lymphoma in China.
AB  - BACKGROUND: The relationships between the expression of ID2, EBV-LMP1 and
      P16(INK4A) in Chinese classical Hodgkin lymphoma are unknown and need exploring.
      METHODS: Samples of classical Hodgkin lymphoma from 60 Chinese patients were
      analyzed for the expression of ID2, EBV-LMP1 and p16(INK4A) proteins by
      immunohistochemistry. RESULTS: ID2 protein was expressed in 83.3% of this group
      of classical Hodgkin lymphoma, staining strongly in both cytoplasm and nucleus of
      the Hodgkin and Reed-Sternberg (HRS) cells. EBV-LMP1 and P16(INK4A) were
      overexpressed in 85.0% and 71.7% of Hodgkin lymphoma, respectively. EBV-LMP1 was
      noted in the cytoplasm, membrane and nucleus of HRS cells; P16(INK4A) was in the
      nucleus and cytoplasm. Microscopically, ID2, EBV-LMP1 and P16(INK4A) staining
      distinguished the HRS cells from the complex background of lymphocytes. ID2 was
      positively correlated with EBV-LMP1(P < 0.01), but P16(INK4A) was inversely
      related to EBV-LMP1 (P < 0.05). CONCLUSION: It is suggested that ID2, EBV-LMP1
      and P16(INK4A) could play an important role in the evolution of classical Hodgkin
      lymphoma, and be considered as potential adjunct markers to identify HRS cells in
      diagnosis.

PMID- 19099555
TI  - Equine Multiple Congenital Ocular Anomalies maps to a 4.9 megabase interval on
      horse chromosome 6.
AB  - BACKGROUND: Equine Multiple Congenital Ocular Anomalies (MCOA) syndrome consists
      of a diverse set of abnormalities predominantly localized to the frontal part of
      the eye. The disease is in agreement with a codominant mode of inheritance in our
      horse material. Animals presumed to be heterozygous for the mutant allele have
      cysts originating from the temporal ciliary body, peripheral retina and/or iris.
      In contrast, animals predicted to be homozygous for the disease-causing allele
      possess a wide range of multiple abnormalities, including iridociliary and/or
      peripheral retinal cysts, iridocorneal angle abnormalities, cornea globosa, iris
      hypoplasia and congenital cataracts. MCOA is most common in the Rocky Mountain
      horse breed where it occurs at a high frequency among Silver colored horses. The
      Silver coat color is associated with mutations in PMEL17 that resides on ECA6q23.
      To map the MCOA locus we analyzed 11 genetic markers on ECA6q and herein describe
      a chromosome interval for the MCOA locus. RESULTS: We performed linkage analysis
      within 17 paternal half-sib families of the Rocky Mountain horse breed. More than
      half of the 131 offspring had the Cyst phenotype and about one third had MCOA.
      Segregation data were obtained by genotyping 10 microsatellite markers most of
      which are positioned on ECA6q22-23, as well as the missense mutation for the
      Silver phenotype in PMEL17. Significant linkage was found between the MCOA locus
      and eight of the genetic markers, where marker UPP5 (Theta = 0, z = 12.3),
      PMEL17ex11 (Theta = 0, z = 19.0) and UPP6 (Theta = 0, z = 17.5) showed complete
      linkage with the MCOA locus. DNA sequencing of PMEL17 in affected and healthy
      control individuals did not reveal any additional mutations than the two
      mutations associated with the Silver coat color. CONCLUSION: The MCOA locus can
      with high confidence be positioned within a 4.9 megabase (Mb) interval on ECA6q.
      The genotype data on UPP5, PMEL17ex11 and UPP6 strongly support the hypothesis
      that horses with the Cyst phenotype are heterozygous for the mutant allele and
      that horses with the MCOA phenotype are homozygous for the mutant allele.

PMID- 19099556
TI  - Phylogenetic distribution and membrane topology of the LytR-CpsA-Psr protein
      family.
AB  - BACKGROUND: The bacterial cell wall is the target of many antibiotics and cell
      envelope constituents are critical to host-pathogen interactions. To combat
      resistance development and virulence, a detailed knowledge of the individual
      factors involved is essential. Members of the LytR-CpsA-Psr family of cell
      envelope-associated attenuators are relevant for beta-lactam resistance, biofilm
      formation, and stress tolerance, and they are suggested to play a role in cell
      wall maintenance. However, their precise function is still unknown. This study
      addresses the occurrence as well as sequence-based characteristics of the LytR
      CpsA-Psr proteins. RESULTS: A comprehensive list of LytR-CpsA-Psr proteins was
      established, and their phylogenetic distribution and clustering into subgroups
      was determined. LytR-CpsA-Psr proteins were present in all Gram-positive
      organisms, except for the cell wall-deficient Mollicutes and one strain of the
      Clostridiales. In contrast, the majority of Gram-negatives did not contain LytR
      CpsA-Psr family members. Despite high sequence divergence, the LytR-CpsA-Psr
      domains of different subclusters shared a highly similar, predicted mixed a/beta
      structure, and conserved charged residues. PhoA fusion experiments, using MsrR of
      Staphylococcus aureus, confirmed membrane topology predictions and extracellular
      location of its LytR-CpsA-Psr domain. CONCLUSION: The LytR-CpsA-Psr domain is
      unique to bacteria. The presence of diverse subgroups within the LytR-CpsA-Psr
      family might indicate functional differences, and could explain variations in
      phenotypes of respective mutants reported. The identified conserved structural
      elements and amino acids are likely to be important for the function of the
      domain and will help to guide future studies of the LytR-CpsA-Psr proteins.

PMID- 19099557
TI  - Clinical utility of genetic tests for inherited hypertrophic and dilated
      cardiomyopathies.
AB  - Genetic testing has become an increasingly important part of medical practice for
      heritable form of cardiomyopathies. Hypertrophic cardiomyopathy and about 50% of
      idiopathic dilatative cardiomyopathy are familial diseases, with an autosomal
      dominant pattern of inheritance.Some genotype-phenotype correlations can provide
      important information to target DNA analyses in specific genes. Genetic testing
      may clarify diagnosis and help the optimal treatment strategies for more
      malignant phenotypes. In addition, genetic screening of first-degree relatives
      can help early identification and diagnosis of individuals at greatest risk for
      developing cardiomyopathy, allowing to focus clinical resources on high-risk
      family members.This paper provides a concise overview of the genetic etiology as
      well as the clinical utilities and limitations of genetic testing for the
      heritable cardiomyopathies.

PMID- 19099558
TI  - A multilocus assay reveals high nucleotide diversity and limited differentiation
      among Scandinavian willow grouse (Lagopus lagopus).
AB  - BACKGROUND: There is so far very little data on autosomal nucleotide diversity in
      birds, except for data from the domesticated chicken and some passerines species.
      Estimates of nucleotide diversity reported so far in birds have been high
      (approximately 10(-3)) and a likely explanation for this is the generally higher
      effective population sizes compared to mammals. In this study, the level of
      nucleotide diversity has been examined in the willow grouse, a non-domesticated
      bird species from the order Galliformes, which also holds the chicken. The willow
      grouse (Lagopus lagopus) has an almost circumpolar distribution but is absent
      from Greenland and the north Atlantic islands. It primarily inhabits tundra,
      forest edge habitats and sub-alpine vegetation. Willow grouse are hunted
      throughout its range, and regionally it is a game bird of great cultural and
      economical importance. RESULTS: We sequenced 18 autosomal protein coding loci
      from approximately 15-18 individuals per population. We found a total of 127
      SNP's, which corresponds to 1 SNP every 51 bp. 26 SNP's were amino acid
      replacement substitutions. Total nucleotide diversity (pit) was between 1.30 x
      10(-4) and 7.66 x 10(-3) (average pi(t) = 2.72 x 10(-3) +/- 2.06 x 10(-3)) and
      silent nucleotide diversity varied between 4.20 x 10(-4) and 2.76 x 10(-2)
      (average pi(S) = 9.22 x 10(-3) +/- 7.43 x 10(-4)). The synonymous diversity is
      approximately 20 times higher than in humans and two times higher than in
      chicken. Non-synonymous diversity was on average 18 times lower than the
      synonymous diversity and varied between 0 and 4.90 x 10(-3) (average pi(a) = 5.08
      x 10(-4) +/- 7.43 x 10(3)), which suggest that purifying selection is strong in
      these genes. F(ST) values based on synonymous SNP's varied between -5.60 x 10(-4)
      and 0.20 among loci and revealed low levels of differentiation among the four
      localities, with an overall value of F(ST) = 0.03 (95% CI: 0.006 - 0.057) over 60
      unlinked loci. Non-synonymous SNP's gave similar results. Low levels of linkage
      disequilibrium were observed within genes, with an average r2 = 0.084 +/- 0.110,
      which is expected for a large outbred population with no population
      differentiation. The mean per site per generation recombination parameter (rho)
      was comparably high (0.028 +/- 0.018), indicating high recombination rates in
      these genes. CONCLUSION: We found unusually high levels of nucleotide diversity
      in the Scandinavian willow grouse as well as very little population structure
      among localities with up to 1647 km distance. There are also low levels of
      linkage disequilibrium within the genes and the population recombination rate is
      high, which is indicative of an old panmictic population, where recombination has
      had time to break up any haplotype blocks. The non-synonymous nucleotide
      diversity is low compared with the silent, which is in agreement with effective
      purifying selection, possibly due to the large effective population size.

PMID- 19099559
TI  - Bad housekeeping: why do aphids leave their exuviae inside the colony?
AB  - BACKGROUND: Animals can gain protection against predators and parasites by living
      in groups. The encounter-dilution effect provides protection when the probability
      of detection of a group does not increase in proportion to group size (i.e.
      encounter effect), so that predators do not offset the encounter effect by
      attacking more members of the group (i.e. dilution effect). In this paper, we
      propose a novel mechanism by which prey insects could gain by producing decoys
      that act as multiple targets for predators or parasitoids if these decoys are
      recognised as preys or hosts and negatively affect the patch foraging strategy of
      these predators and parasitoids. Such a decoy mechanism could be present in aphid
      colonies in which aphid exuviae are recognised and attacked by Aphidiine wasps.
      RESULTS: We conducted a behavioural study to evaluate the effect of exuviae on
      parasitoid patch residence time and egg allocation in experimental aphid patches
      with or without exuviae. We showed that exuviae are recognised and attacked at
      the same level as aphids when both are present in the patch. While parasitism
      rate was not significantly lower in patches with exuviae when the parasitoid left
      the patch, the time wasted by parasitoids to handle exuviae did influence the
      patch residence time. As a consequence, the attack rate on the live aphids was
      lower in patches that contain exuviae. CONCLUSION: Aphids had more time available
      to flee and thus each individual might gain protection against parasitoids by
      leaving their exuviae near and within the colony. These results demonstrate that
      the encounter-dilution effect provided by living in a group can be enhanced by
      extra-materials that act as decoy for natural enemies.

PMID- 19099560
TI  - Malignant mesothelioma.
AB  - Malignant mesothelioma is a fatal asbestos-associated malignancy originating from
      the lining cells (mesothelium) of the pleural and peritoneal cavities, as well as
      the pericardium and the tunica vaginalis. The exact prevalence is unknown but it
      is estimated that mesotheliomas represent less than 1% of all cancers. Its
      incidence is increasing, with an expected peak in the next 10-20 years. Pleural
      malignant mesothelioma is the most common form of mesothelioma. Typical
      presenting features are those of chest pain and dyspnoea. Breathlessness due to a
      pleural effusion without chest pain is reported in about 30% of patients. A chest
      wall mass, weight loss, sweating, abdominal pain and ascites (due to peritoneal
      involvement) are less common presentations. Mesothelioma is directly attributable
      to occupational asbestos exposure with a history of exposure in over 90% of
      cases. There is also evidence that mesothelioma may result from both para
      occupational exposure and non-occupational "environmental" exposure. Idiopathic
      or spontaneous mesothelioma can also occur in the absence of any exposure to
      asbestos, with a spontaneous rate in humans of around one per million. A
      combination of accurate exposure history, along with examination radiology and
      pathology are essential to make the diagnosis. Distinguishing malignant from
      benign pleural disease can be challenging. The most helpful CT findings
      suggesting malignant pleural disease are 1) a circumferential pleural rind, 2)
      nodular pleural thickening, 3) pleural thickening of > 1 cm and 4) mediastinal
      pleural involvement. Involvement of a multidisciplinary team is recommended to
      ensure prompt and appropriate management, using a framework of radiotherapy,
      chemotherapy, surgery and symptom palliation with end of life care. Compensation
      issues must also be considered. Life expectancy in malignant mesothelioma is
      poor, with a median survival of about one year following diagnosis.

PMID- 19099562
TI  - Caudal regression syndrome and popliteal webbing in connection with maternal
      diabetes mellitus: a case report and literature review.
AB  - INTRODUCTION: Most cases of caudal regression are sporadic or associated with
      gestational/maternal diabetes. The condition is thought to be part of a spectrum
      including imperforate anus, sacral agenesis and sirenomelia. Infants of diabetic
      mothers have two to three times the average incidence of congenital anomalies.
      CASE PRESENTATION: We report on a 7-year-old boy from non-consanguineous family
      in Austria was born with features of caudal regression syndrome. A constellation
      of malformation complex such as caudal regression syndrome and anorectal
      malformation complex were evident at birth. Of great interest was the abnormal
      articulation between the pelvis and the remaining abnormal spine. Spinal-pelvic
      instability, dislocation of the hip, and knee-flexion contracture associated with
      popliteal webbing were the major orthopaedic abnormalities. CONCLUSION: We showed
      that an offspring of a diabetic mother was at significant risk of developing
      caudal regression syndrome. Our present patient demonstrated type1 of Welch and
      Aterman classification. There was total sacral agenesis associated with subtotal
      lumbar agenesis. The lowest vertebrae were resting above an iliac amphiathrosis.
      We strongly encourage primary care providers to discuss the consequences of
      maternal diabetes mellitus as part of routine anticipatory guidance for
      antenatal/prenatal management. Careful diabetic control in the preconceptional
      period and the first eight weeks of pregnancy may lower the chances of congenital
      anomalies.

PMID- 19099561
TI  - Role of cAMP in the promotion of colorectal cancer cell growth by prostaglandin
      E2.
AB  - BACKGROUND: Prostaglandin E2 (PGE2), a product of the cyclooxygenase (COX)
      reaction, stimulates the growth of colonic epithelial cells. It is inferred that
      the abrogation of prostaglandins' growth-promoting effects as a result of COX
      inhibition underlies the advantageous effects of non-steroidal anti-inflammatory
      drugs in colorectal carcinoma (CRC). Despite this appreciation, the underlying
      molecular mechanisms remain obscure since cell culture studies have yielded
      discrepant results regarding PGE2's mitogenicity. METHODS: We have employed
      several alternative approaches to score cell proliferation and apoptosis of 4 CRC
      cell lines exposed to PGE2 under various conditions. To investigate the role of
      cAMP in PGE2's functions, activation of the cAMP pathway was assessed at
      different levels (changes in cAMP levels and PKA activity) in cells subjected to
      specific manipulations including the use of specific inhibitors or prostanoid
      receptor-selective agonists/antagonists. RESULTS: Our data document that the dose
      response curve to PGE2 is 'bell-shaped', with nano molar concentrations of PGE2
      being more mitogenic than micro molar doses. Remarkably, mitogenicity inversely
      correlates with the ability of PGE2 doses to raise cAMP levels. Consistent with a
      major role for cAMP, cAMP raising agents and pertussis toxin revert the mitogenic
      response to PGE2. Accordingly, use of prostanoid receptor-selective agonists
      argues for the involvement of the EP3 receptor and serum deprivation of HT29 CRC
      cells specifically raises the levels of Gi-coupled EP3 splice variants.
      CONCLUSION: The present data indicate that the mitogenic action of low PGE2 doses
      in CRC cells is mediated via Gi-proteins, most likely through the EP3 receptor
      subtype, and is superimposed by a second, cAMP-dependent anti-proliferative
      effect at higher PGE2 doses. We discuss how these findings contribute to
      rationalize conflictive literature data on the proliferative action of PGE2.

PMID- 19099563
TI  - Cryptogenic hepatic insult, failing heart and advancing age: a case report.
AB  - BACKGROUND: Weakness and fatigue are accepted as normal accompaniments of aging.
      Usually, older individuals are not investigated with much enthusiasm but a
      treatable cause is discernible on several occasions. CASE PRESENTATION: We had a
      67 year old hypertensive lady with a mitral stenosis, presenting in ischemic or
      hypertensive heart failure with underlying valvular disease, without pulmonary
      hypertension in sinus rhythm. She had pancytopenia with severe anemia and raised
      liver enzymes. Bone marrow examination showed aplastic anemia. She was treated
      with ATG and improved subsequently to become transfusion free. However, she
      succumbed to an unrelated sudden cardiac death. CONCLUSION: Our patient is unique
      in her uncommon presentation, complex management issues and a favorable outcome
      after a long and persevering therapeutic intervention and finally her sudden
      death.

PMID- 19099564
TI  - The prognostic relevance of interactions between venous invasion, lymph node
      involvement and distant metastases in renal cell carcinoma after radical
      nephrectomy.
AB  - BACKGROUND: To investigate a possible prognostic significance of interactions
      between lymph node invasion (LNI), synchronous distant metastases (SDM), and
      venous invasion (VI) adjusted for mode of detection, Eastern Cooperative Oncology
      Group performance status (ECOG PS), erythrocyte sedimentation rate (ESR) and
      tumour size (TS) in 196 patients with renal cell carcinoma treated with radical
      nephrectomy. METHODS: Median follow-up was 5.5 years (mean 6.9 years; range 0.01
      19.4). The mode of detection, ECOG PS, ESR and TS were obtained from the
      patients' records. Vena cava invasion and distant metastases were detected by
      preoperative imaging. The surgical specimens were examined for pathological
      stage, LNI and VI. RESULTS: The univariate analyses showed significant impact of
      VI, LNI, SDM, ESR and TS (p < 0.001), as well as mode of detection (p = 0.003)
      and ECOG PS (p = 0.002) on cancer specific survival. In multivariate analyses LNI
      was significantly associated with survival only in patients without SDM or VI (p
      < 0.001) with a hazard ratio of 9.0. LNI lost its prognostic significance when
      SDM or VI was present. CONCLUSION: Our findings underline the prognostic
      importance of the status of the lymph nodes. LNI, SDM, ESR, and VI were
      independently associated with cancer specific survival after radical nephrectomy.
      LNI provided the strongest prognostic information for patients without SDM or VI
      whereas SDM and VI had strongest impact on survival when there was no nodal
      involvement.

PMID- 19099565
TI  - Phylogeography and historical demography of the Lusitanian snail Elona
      quimperiana reveal survival in unexpected separate glacial refugia.
AB  - BACKGROUND: Present day distributions of Palearctic taxa in northern latitudes
      mainly result from populations having survived in local patches during the Late
      Pleistocene and/or from recolonizing populations from southern temperate refugia.
      If well-studied Mediterranean and eastern European refugia are widely accepted,
      some recent biogeographical assumptions still remain unclear, such as the
      occurrence of multiple glacial refugia in Iberia and cryptic refugia in northern
      Europe during the last glaciations. The Lusitanian snail Elona quimperiana has a
      remarkably disjunct distribution, limited to northwestern France (Brittany),
      northwestern Spain and the Basque Country. By describing the phylogeographical
      structure of this species across its entire range, the present study attempts to
      identify refugia and subsequent recolonization routes. RESULTS: Results based on
      16S and COI gene sequences showed that the low genetic diversity observed in the
      Brittany populations should be associated with a recent demographic expansion. By
      contrast, populations from Spain exhibit several differentiated lineages and are
      characterized by demographic equilibrium, while the Basque populations are the
      only ones harboring typical distinct haplotypes. The center of the star-like
      networks of both gene sequences is occupied by a common ancestral-like haplotype
      found in Brittany and Spain, which might have originated from the middle of
      Northern Spain (i.e. Asturias, eastern Lugo and western Cantabria). Estimates of
      the divergence time between the Spain-Brittany and Basque lineages strongly
      suggest that E. quimperiana survived the Pleistocene glaciations in distinct
      refugia on the Iberian Peninsula, one of which is situated in Picos de Europa,
      and the other in the Basque Country. The occurrence of a northern refugium in
      France cannot be rejected as of yet. CONCLUSION: Present results confirm the
      Iberian origin of the land snail E. quimperiana and strongly support the emerging
      phylogeographic hypothesis of multiple refugia in Iberia during the last
      glaciations. The scenario of a spatial expansion of E. quimperiana from an
      Iberian refuge located in Asturias to northern areas provides the most probable
      explanation for the present distribution of this land snail. By harboring
      distinct haplotypes, the Basque Country populations appear to be of great
      importance in terms of potential adaptation, long term persistence and hence, the
      conservation of E. quimperiana.

PMID- 19099566
TI  - Cryptic speciation in a benthic isopod from Patagonian and Falkland Island waters
      and the impact of glaciations on its population structure.
AB  - BACKGROUND: The Falkland Islands and Patagonia are traditionally assigned to the
      Magellan Biogeographic Province. Most marine species in Falkland waters are also
      reported from southern Patagonia. It remains unclear if relatively immobile,
      marine benthic, shallow-water species maintain gene flow, and by what mechanism.
      Recurrent fluctuations in sea level during glacial cycles are regarded as a
      possible mechanism that might have allowed genetic exchange between the regions.
      However, the realized genetic exchange between the Falkland Islands and Patagonia
      has never been estimated. RESULTS: This study analyses the genetic structure of
      three populations of the marine shallow-water isopod Serolis paradoxa (Fabricius,
      1775) from the Falkland Islands and southern Patagonia (central Strait of
      Magellan and the Atlantic opening) applying seven nuclear microsatellites and a
      fragment of the mitochondrial 16S rRNA gene. Both marker systems report highest
      genetic diversity for the population from the central Strait of Magellan and
      lowest for the Falkland Islands. The estimated effective population sizes were
      large for all populations studied. Significant differentiation was observed among
      all three populations. The magnitude of differentiation between Patagonia and the
      Falkland Islands (16S: uncorrected p-distance 2.1%; microsatellites: standardized
      F'ST > 0.86) was an order of magnitude higher than between populations from
      within Patagonia. This indicates that there is currently no effective gene flow
      for nominal S. paradoxa between these two regions and it has been absent for time
      exceeding the last glacial maximum. We argue that specimens from the Strait of
      Magellan and the Falkland Islands very likely represent two distinct species that
      separated in the mid-Pleistocene (about 1 MY BP). CONCLUSION: The results of this
      study indicate limited gene flow between distant populations of the brooding
      isopod Serolis paradoxa. The patterns of genetic diversity suggest that the only
      recently inundated Strait of Magellan was colonized by different source
      populations, most likely from Atlantic and Pacific coastal waters. Our results
      demonstrate that more systematic testing of shared faunal inventory and realized
      genetic exchange between Patagonia and the Falkland Islands is needed before a
      consensus concerning the position of the Falkland Islands relative to the
      Magellan zoogeographic province can be reached.

PMID- 19099567
TI  - Monocytes are essential for inhibition of synovial T-cell glucocorticoid-mediated
      apoptosis in rheumatoid arthritis.
AB  - INTRODUCTION: Rheumatoid arthritis (RA) is characterized by synovial inflammation
      with local accumulation of mononuclear cells such as macrophages and lymphocytes.
      We previously demonstrated that intra-articular glucocorticoids decrease the
      synovial tissue (ST) T-cell population and therefore aimed to investigate whether
      this is mediated through modulation of apoptosis. METHODS: Apoptosis and cell
      phenotype were evaluated by immunohistochemistry and dual-immunofluorescence in
      synovial biopsy sections from 12 RA patients before and after a mean of 11 days
      of an intra-articular triamcinolone knee injection. In vitro, RA synovial fluid
      (SF)-derived T cells were evaluated for Annexin V expression by multicolor flow
      cytometry after 24-hour exposure to dexamethasone, methylprednisolone, or
      triamcinolone. We also tested induction of apoptosis by dexamethasone on
      psoriatic arthritis SF-derived T cells using the same method. RESULTS: Intra
      articular glucocorticoids reduced ST T cells but not macrophage number. ST
      apoptosis levels were unchanged following treatment, virtually absent from
      lymphoid aggregates, and minimal in CD3+ cells both before and after treatment.
      RA SF T cells were resistant to glucocorticoid-induced apoptosis when cultured in
      the presence of monocytes but were rendered sensitive to all three tested
      compounds upon SF isolation. Furthermore, transwell coculture of monocytes and T
      cells demonstrated that soluble factor(s) and not cellular contact are essential
      for T-cell resistance to glucocorticoid-mediated apoptosis. This feature is RA
      specific as far as dexamethasone-induced apoptosis in nonisolated SF T cells
      obtained from psoriatic arthritis patients is concerned. CONCLUSIONS: We
      demonstrate that monocytes rescue synovial T cells from glucocorticoid-induced
      apoptosis, a feature that is specific for RA. To overcome this, we propose the
      use of monocyte-targeted therapies rather than T-cell apoptosis-inducing
      therapies.

PMID- 19099568
TI  - Expressing gait-line symmetry in able-bodied gait.
AB  - BACKGROUND: Gait-lines, or the co-ordinates of the progression of the point of
      application of the vertical ground reaction force, are a commonly reported
      parameter in most in-sole measuring systems. However, little is known about what
      is considered a "normal" or "abnormal" gait-line pattern or level of asymmetry.
      Furthermore, no reference databases on healthy young populations are available
      for this parameter. Thus the aim of this study is to provide such reference data
      in order to allow this tool to be better used in gait analysis. METHODS: Vertical
      ground reaction force data during several continuous gait cycles were collected
      using a Computer Dyno Graphy in-sole system for 77 healthy young able-bodied
      subjects. A curve (termed gait-line) was obtained from the co-ordinates of the
      progression of the point of application of the force. An Asymmetry Coefficient
      Curve (AsC) was calculated between the mean gait-lines for the left and right
      foot for each subject. AsC limits of +/- 1.96 and 3 standard deviations (SD) from
      the mean were then calculated. Gait-line data from 5 individual subjects
      displaying pathological gait due to disorders relating to the discopathy of the
      lumbar spine (three with considerable plantarflexor weakness, two with
      considerable dorsiflexor weakness) were compared to the AsC results from the able
      bodied group. RESULTS: The +/- 1.96 SD limit suggested that non-pathological gait
      falls within 12-16% asymmetry for gait-lines. Those exhibiting pathological gait
      fell outside both the +/- 1.96 and +/- 3SD limits at several points during
      stance. The subjects exhibiting considerable plantarflexor weakness all fell
      outside the +/- 1.96SD limit from 30-50% of foot length to toe-off while those
      exhibiting considerable dorsiflexor weakness fell outside the +/- 1.96SD limit
      between initial contact to 25-40% of foot length, and then surpassed the +/- 3SD
      limit after 55-80% of foot length. CONCLUSION: This analysis of gait-line
      asymmetry provides a reference database for young, healthy able-bodied subject
      populations for both further research and clinical gait analysis. This
      information is used to suggest non-pathological gait-line asymmetry pattern
      limits, and limits where detailed case analysis is warranted.

PMID- 19099570
TI  - Treatments for irritable bowel syndrome: patients' attitudes and acceptability.
AB  - BACKGROUND: Irritable Bowel Syndrome, a highly prevalent chronic disorder, places
      significant burden on the health service and the individual. Symptomatic distress
      and reduced quality of life are compounded by few efficacious treatments
      available. As researchers continue to demonstrate the clinical efficacy of
      alternative therapies, it would be useful to gain a patient-perspective of
      treatment acceptability and identify patient's attitudes towards those modalities
      considered not acceptable. METHODS: Six hundred and forty-five participants
      identified from an earlier IBS-prevalence study received a postal questionnaire
      to evaluate preferences and acceptability of nine forms of treatment. Proportions
      accepting each form of treatment were calculated and thematic analysis of
      qualitative data undertaken. RESULTS: A total of 256 (39.7%) of 645 potential
      respondents completed the questionnaire (mean age 55.9 years, 73% female).
      Tablets were most acceptable (84%), followed by lifestyle changes (diet (82%),
      yoga (77%)). Acupuncture (59%) and suppositories (57%) were less acceptable. When
      explaining lack of acceptability, patient views fell into four broad categories:
      dislike treatment modality, do not perceive benefit, general barriers and
      insufficient knowledge. Scepticism, lack of scientific rationale and fear of CAM
      were mentioned, although others expressed a dislike of conventional medical
      treatments. Past experiences, age and health concerns, and need for proof of
      efficacy were reported. CONCLUSION: Most patients were willing to accept various
      forms of treatment. However, the reservations expressed by this patient
      population must be recognised with particular focus directed towards allaying
      fears and misconceptions, seeking further evidence base for certain therapies and
      incorporating physician support and advice.

PMID- 19099569
TI  - Development of a screening tool predicting the transition from acute to chronic
      low back pain for patients in a GP setting: protocol of a multinational
      prospective cohort study.
AB  - BACKGROUND: Low back pain (LBP) is by far the most prevalent and costly
      musculoskeletal problem in our society today. Following the recommendations of
      the Multinational Musculoskeletal Inception Cohort Study (MMICS) Statement, our
      study aims to define outcome assessment tools for patients with acute LBP and the
      time point at which chronic LBP becomes manifest and to identify patient
      characteristics which increase the risk of chronicity. METHODS: Patients with
      acute LBP will be recruited from clinics of general practitioners (GPs) in New
      Zealand (NZ) and Switzerland (CH). They will be assessed by postal survey at
      baseline and at 3, 6, 12 weeks and 6 months follow-up. Primary outcome will be
      disability as measured by the Oswestry Disability Index (ODI); key secondary
      endpoints will be general health as measured by the acute SF-12 and pain as
      measured on the Visual Analogue Scale (VAS). A subgroup analysis of different
      assessment instruments and baseline characteristics will be performed using
      multiple linear regression models. This study aims to examine: 1. Which
      biomedical, psychological, social, and occupational outcome assessment tools are
      identifiers for the transition from acute to chronic LBP and at which time point
      this transition becomes manifest. 2. Which psychosocial and occupational baseline
      characteristics like work status and period of work absenteeism influence the
      course from acute to chronic LBP. 3. Differences in outcome assessment tools and
      baseline characteristics of patients in NZ compared with CH. DISCUSSION: This
      study will develop a screening tool for patients with acute LBP to be used in GP
      clinics to access the risk of developing chronic LBP. In addition, biomedical,
      psychological, social, and occupational patient characteristics which influence
      the course from acute to chronic LBP will be identified. Furthermore, an
      appropriate time point for follow-ups will be given to detect this transition.
      The generalizability of our findings will be enhanced by the international
      perspective of this study. TRIAL REGISTRATION: [Clinical Trial Registration
      Number, ACTRN12608000520336].

PMID- 19099571
TI  - A study of young peoples' attitudes to opportunistic Chlamydia testing in UK
      general practice.
AB  - OBJECTIVE: The objective of this study was to assess young people's perceptions
      of being offered a chlamydia screening test in United Kingdom (UK) general
      practice. METHODS: This is qualitative study that uses focus groups and
      individual interviews with young adults (age 16 - 18) to assess their views.
      RESULTS: These young adults were a difficult group to gain access to. Two focus
      groups, one in a school, the other in a general practice (family practice), and 2
      individual interviews were undertaken (total sample 18). Respondents were
      unfamiliar with Chlamydia, but broadly aware of sexually transmitted infections.
      General practice (family practice) was perceived as an acceptable place to
      deliver opportunistic screening, but participants felt that tests should not be
      initiated by GP receptionists. Novel delivery routes such as schools and
      "Pub"/Bar dispensing machines were discussed. Issues around stigma and
      confidentiality were also raised. CONCLUSION: Opportunistic Chlamydia screening
      in UK general practice (family practic seems acceptable to young adults. While
      this is a difficult group to gain access to for research, attempts need to made
      to ensure acceptability to users of this programme.

PMID- 19099572
TI  - Blind search for post-translational modifications and amino acid substitutions
      using peptide mass fingerprints from two proteases.
AB  - BACKGROUND: Mass spectrometric analysis of peptides is an essential part of
      protein identification and characterization, the latter meaning the
      identification of modifications and amino acid substitutions. There are two main
      approaches for characterization: (i) using a predefined set of possible
      modifications and substitutions or (ii) performing a blind search. The first
      option is straightforward, but can not detect modifications or substitutions
      outside the predefined set. A blind search does not have this limitation, and
      therefore has the potential of detecting both known and unknown modifications and
      substitutions. Combining the peptide mass fingerprints from two proteases result
      in overlapping sequence coverage of the protein, thereby offering alternative
      views of the protein and a novel way of indicating post-translational
      modifications and amino acid substitutions. RESULTS: We have developed an
      algorithm and a software tool, MassShiftFinder, that performs a blind search
      using peptide mass fingerprints from two proteases with different cleavage
      specificities. The algorithm is based on equal mass shifts for overlapping
      peptides from the two proteases used, and can indicate both post-translational
      modifications and amino acid substitutions. In most cases it is possible to
      suggest a restricted area within the overlapping peptides where the mass shift
      can occur. The program is available at
      http://www.bioinfo.no/software/massShiftFinder. CONCLUSION: Without any prior
      assumptions on their presence the described algorithm is able to indicate post
      translational modifications or amino acid substitutions in MALDI-TOF experiments
      on identified proteins, and can thereby direct the involved peptides to
      subsequent TOF-TOF analysis. The algorithm is designed for detailed and low
      throughput characterization of single proteins.

PMID- 19099573
TI  - EZH2 and BMI1 inversely correlate with prognosis and TP53 mutation in breast
      cancer.
AB  - INTRODUCTION: PolycombGroup (PcG) proteins maintain gene repression through
      histone modifications and have been implicated in stem cell regulation and
      cancer. EZH2 is part of Polycomb Repressive Complex 2 (PRC2) and trimethylates
      H3K27. This histone mark recruits the BMI1-containing PRC1 that silences the
      genes marked by PRC2. Based on their role in stem cells, EZH2 and BMI1 have been
      predicted to contribute to a poor outcome for cancer patients. METHODS: We have
      analysed the expression of EZH2 and BMI1 in a well-characterised dataset of 295
      human breast cancer samples. RESULTS: Interestingly, although EZH2 overexpression
      correlates with a poor prognosis in breast cancer, BMI1 overexpression correlates
      with a good outcome. Although this may reflect transformation of different cell
      types, we also observed a functional difference. The PcG-target genes INK4A and
      ARF are not expressed in tumours with high BMI1, but they are expressed in
      tumours with EZH2 overexpression. ARF expression results in tumour protein P53
      (TP53) activation, and we found a significantly higher proportion of TP53
      mutations in tumours with high EZH2. This may explain why tumours with high EZH2
      respond poorly to therapy, in contrast to tumours with high BMI1. CONCLUSIONS:
      Overall, our data highlight that whereas EZH2 and BMI1 may function in a 'linear'
      pathway in normal development, their overexpression has different functional
      consequences for breast tumourigenesis.

PMID- 19099574
TI  - Functional health status in subjects after a motor vehicle accident, with
      emphasis on whiplash associated disorders: design of a descriptive, prospective
      inception cohort study.
AB  - BACKGROUND: The clinical consequences of whiplash injuries resulting from a motor
      vehicle accident (MVA) are poorly understood. Thereby, there is general lack of
      research on the development of disability in patients with acute and chronic
      Whiplash Associated Disorders. METHODS/DESIGN: The objective is to describe the
      design of an inception cohort study with a 1-year follow-up to determine risk
      factors for the development of symptoms after a low-impact motor vehicle
      accident, the prognosis of chronic disability, and costs. Victims of a low-impact
      motor vehicle accident will be eligible for participation. Participants with a
      Neck Disability Index (NDI) score of 7 or more will be classified as experiencing
      post-traumatic neck pain and will enter the experimental group. Participants
      without complaints (a NDI score less than 7) will enter the reference group. The
      cohort will be followed up by means of postal questionnaires and physical
      examinations at baseline, 3 months, 6 months, and 12 months. Recovery from
      whiplash-associated disorders will be measured in terms of perceived functional
      health, and employment status (return to work). Life tables will be generated to
      determine the 1-year prognosis of whiplash-associated disorders, and risk factors
      and prognostic factors will be assessed using multiple logistic regression
      analysis. DISCUSSION: Little is known about the development of symptoms and
      chronic disability after a whiplash injury. In the clinical setting, it is
      important to identify those people who are at risk of developing chronic
      symptoms.This inception prospective cohort study will provide insight in the
      influence of risk factors, of the development of functional health problems, and
      costs in people with whiplash-associated disorders.

PMID- 19099576
TI  - Severe QT interval prolongation associated with moxifloxacin: a case report.
AB  - INTRODUCTION: The QT interval prolongation is an adverse effect associated with
      moxifloxacin. This adverse effect can lead to potentially life-threatening
      arrhythmias such as Torsades de pointes. We describe a case of severe QT interval
      prolongation associated with moxifloxacin which may cause the development of
      Torsades de pointes. There have been no reported case of severe corrected QT
      interval prolongation caused by moxifloxacin in the patient of normal heart rate.
      CASE PRESENTATION: In an 85-year-old Japanese woman, oral moxifloxacin 400 mg
      daily was initiated for the forearm cellulitis. On the sixth day of oral
      moxifloxacin administration, monitor electrocardiogram showed prolongation of the
      corrected QT interval to 523 ms at a rate of 40 beats/min. Electrocardiogram
      before moxifloxacin therapy showed the corrected QT interval to 460 ms at a rate
      of 72 beats/min. On the sixth day after moxifloxacin discontinuance, monitor
      electrocardiogram showed the corrected QT interval to 432 ms at a rate of 70
      beats/min. CONCLUSION: This case suggests that electrocardiogram monitoring
      during moxifloxacin therapy may be necessary in the patients even if they do not
      have high risk factors for QT interval prolongation.

PMID- 19099575
TI  - Common errors and clinical guidelines for manual muscle testing: "the arm test"
      and other inaccurate procedures.
AB  - BACKGROUND: The manual muscle test (MMT) has been offered as a chiropractic
      assessment tool that may help diagnose neuromusculoskeletal dysfunction. We
      contend that due to the number of manipulative practitioners using this test as
      part of the assessment of patients, clinical guidelines for the MMT are required
      to heighten the accuracy in the use of this tool. OBJECTIVE: To present essential
      operational definitions of the MMT for chiropractors and other clinicians that
      should improve the reliability of the MMT as a diagnostic test. Controversy about
      the usefulness and reliability of the MMT for chiropractic diagnosis is ongoing,
      and clinical guidelines about the MMT are needed to resolve confusion regarding
      the MMT as used in clinical practice as well as the evaluation of experimental
      evidence concerning its use. DISCUSSION: We expect that the resistance to accept
      the MMT as a reliable and valid diagnostic tool will continue within some
      portions of the manipulative professions if clinical guidelines for the use of
      MMT methods are not established and accepted. Unreliable assessments of this
      method of diagnosis will continue when non-standard MMT research papers are
      considered representative of the methods used by properly trained clinicians.
      CONCLUSION: Practitioners who employ the MMT should use these clinical guidelines
      for improving their use of the MMT in their assessments of muscle dysfunction in
      patients with musculoskeletal pain.

PMID- 19099577
TI  - Isolation and characterization of microsatellite markers from the olive fly,
      Bactrocera oleae, and their cross-species amplification in the Tephritidae
      family.
AB  - BACKGROUND: The Tephritidae family of insects includes the most important
      agricultural pests of fruits and vegetables, belonging mainly to four genera
      (Bactrocera, Ceratitis, Anastrepha and Rhagoletis). The olive fruit fly,
      Bactrocera oleae, is the major pest of the olive fruit. Currently, its control is
      based on chemical insecticides. Environmentally friendlier methods have been
      attempted in the past (Sterile Insect Technique), albeit with limited success.
      This was mainly attributed to the lack of knowledge on the insect's behaviour,
      ecology and genetic structure of natural populations. The development of
      molecular markers could facilitate the access in the genome and contribute to the
      solution of the aforementioned problems. We chose to focus on microsatellite
      markers due to their abundance in the genome, high degree of polymorphism and
      easiness of isolation. RESULTS: Fifty-eight microsatellite-containing clones were
      isolated from the olive fly, Bactrocera oleae, bearing a total of sixty-two
      discrete microsatellite motifs. Forty-two primer pairs were designed on the
      unique sequences flanking the microsatellite motif and thirty-one of them
      amplified a PCR product of the expected size. The level of polymorphism was
      evaluated against wild and laboratory flies and the majority of the markers
      (93.5%) proved highly polymorphic. Thirteen of them presented a unique position
      on the olive fly polytene chromosomes by in situ hybridization, which can serve
      as anchors to correlate future genetic and cytological maps of the species, as
      well as entry points to the genome. Cross-species amplification of these markers
      to eleven Tephritidae species and sequencing of thirty-one of the amplified
      products revealed a varying degree of conservation that declines outside the
      Bactrocera genus. CONCLUSION: Microsatellite markers are very powerful tools for
      genetic and population analyses, particularly in species deprived of any other
      means of genetic analysis. The presented set of microsatellite markers possesses
      all features that would render them useful in such analyses. This could also
      prove helpful for species where SIT is a desired outcome, since the development
      of effective SIT can be aided by detailed knowledge at the genetic and molecular
      level. Furthermore, their presented efficacy in several other species of the
      Tephritidae family not only makes them useful for their analysis but also
      provides tools for phylogenetic comparisons among them.

PMID- 19099578
TI  - nGASP--the nematode genome annotation assessment project.
AB  - BACKGROUND: While the C. elegans genome is extensively annotated, relatively
      little information is available for other Caenorhabditis species. The nematode
      genome annotation assessment project (nGASP) was launched to objectively assess
      the accuracy of protein-coding gene prediction software in C. elegans, and to
      apply this knowledge to the annotation of the genomes of four additional
      Caenorhabditis species and other nematodes. Seventeen groups worldwide
      participated in nGASP, and submitted 47 prediction sets across 10 Mb of the C.
      elegans genome. Predictions were compared to reference gene sets consisting of
      confirmed or manually curated gene models from WormBase. RESULTS: The most
      accurate gene-finders were 'combiner' algorithms, which made use of transcript-
      and protein-alignments and multi-genome alignments, as well as gene predictions
      from other gene-finders. Gene-finders that used alignments of ESTs, mRNAs and
      proteins came in second. There was a tie for third place between gene-finders
      that used multi-genome alignments and ab initio gene-finders. The median gene
      level sensitivity of combiners was 78% and their specificity was 42%, which is
      nearly the same accuracy reported for combiners in the human genome. C. elegans
      genes with exons of unusual hexamer content, as well as those with unusually many
      exons, short exons, long introns, a weak translation start signal, weak splice
      sites, or poorly conserved orthologs posed the greatest difficulty for gene
      finders. CONCLUSION: This experiment establishes a baseline of gene prediction
      accuracy in Caenorhabditis genomes, and has guided the choice of gene-finders for
      the annotation of newly sequenced genomes of Caenorhabditis and other nematode
      species. We have created new gene sets for C. briggsae, C. remanei, C. brenneri,
      C. japonica, and Brugia malayi using some of the best-performing gene-finders.

PMID- 19099579
TI  - Male reproductive development: gene expression profiling of maize anther and
      pollen ontogeny.
AB  - BACKGROUND: During flowering, central anther cells switch from mitosis to
      meiosis, ultimately forming pollen containing haploid sperm. Four rings of
      surrounding somatic cells differentiate to support first meiosis and later pollen
      dispersal. Synchronous development of many anthers per tassel and within each
      anther facilitates dissection of carefully staged maize anthers for transcriptome
      profiling. RESULTS: Global gene expression profiles of 7 stages representing 29
      days of anther development are analyzed using a 44 K oligonucleotide array
      querying approximately 80% of maize protein-coding genes. Mature haploid pollen
      containing just two cell types expresses 10,000 transcripts. Anthers contain 5
      major cell types and express >24,000 transcript types: each anther stage
      expresses approximately 10,000 constitutive and approximately 10,000 or more
      transcripts restricted to one or a few stages. The lowest complexity is present
      during meiosis. Large suites of stage-specific and co-expressed genes are
      identified through Gene Ontology and clustering analyses as functional classes
      for pre-meiotic, meiotic, and post-meiotic anther development. MADS box and zinc
      finger transcription factors with constitutive and stage-limited expression are
      identified. CONCLUSIONS: We propose that the extensive gene expression of anther
      cells and pollen represents the key test of maize genome fitness, permitting
      strong selection against deleterious alleles in diploid anthers and haploid
      pollen. Because flowering plants show a substantial bias for male-sterile
      compared to female-sterile mutations, we propose that this fitness test is
      general. Because both somatic and germinal cells are transcriptionally quiescent
      during meiosis, we hypothesize that successful completion of meiosis is required
      to trigger maturation of anther somatic cells.

PMID- 19099580
TI  - A genome-wide screen for modifiers of transgene variegation identifies genes with
      critical roles in development.
AB  - BACKGROUND: Some years ago we established an N-ethyl-N-nitrosourea screen for
      modifiers of transgene variegation in the mouse and a preliminary description of
      the first six mutant lines, named MommeD1-D6, has been published. We have
      reported the underlying genes in three cases: MommeD1 is a mutation in SMC hinge
      domain containing 1 (Smchd1), a novel modifier of epigenetic gene silencing;
      MommeD2 is a mutation in DNA methyltransferase 1 (Dnmt1); and MommeD4 is a
      mutation in Smarca 5 (Snf2h), a known chromatin remodeler. The identification of
      Dnmt1 and Smarca5 attest to the effectiveness of the screen design. RESULTS: We
      have now extended the screen and have identified four new modifiers, MommeD7-D10.
      Here we show that all ten MommeDs link to unique sites in the genome, that
      homozygosity for the mutations is associated with severe developmental
      abnormalities and that heterozygosity results in phenotypic abnormalities and
      reduced reproductive fitness in some cases. In addition, we have now identified
      the underlying genes for MommeD5 and MommeD10. MommeD5 is a mutation in Hdac1,
      which encodes histone deacetylase 1, and MommeD10 is a mutation in Baz1b (also
      known as Williams syndrome transcription factor), which encodes a transcription
      factor containing a PHD-type zinc finger and a bromodomain. We show that
      reduction in the level of Baz1b in the mouse results in craniofacial features
      reminiscent of Williams syndrome. CONCLUSIONS: These results demonstrate the
      importance of dosage-dependent epigenetic reprogramming in the development of the
      embryo and the power of the screen to provide mouse models to study this process.

PMID- 19099581
TI  - An overview of molecular epidemiology of hepatitis B virus (HBV) in India.
AB  - Hepatitis B virus (HBV) is one of the major global public health problems. In
      India, HBsAg prevalence among general population ranges from 2% to 8%, placing
      India in intermediate HBV endemicity zone and the number of HBV carriers is
      estimated to be 50 million, forming the second largest global pool of chronic HBV
      infections. India is a vast country, comprised of multiracial communities with
      wide variations in ethnicity and cultural patterns, which is attributable to its
      geographical location, gene influx due to invasion and/or anthropological
      migrations in the past. Moreover, recent increase in trade, trafficking and use
      of illicit drugs has also considerably influenced the epidemiology of HBV,
      specifically in the eastern and north eastern parts of India. However, data on
      the molecular epidemiology of HBV in India is scanty. HBV genotypes A and D have
      been well documented from different parts of mainland India. Interestingly, in
      addition to genotypes A and D, genotype C having high nucleotide similarity with
      south East Asian subgenotype Cs/C1 strain, have been detected exclusively from
      eastern Indian HBV carriers, suggesting a recent introduction. Thus, compared to
      other parts of India, the molecular epidemiology of HBV is naturally distinct in
      eastern India. Very recently, taking the advantage of circulation of three
      distinct HBV genotypes within the population of eastern India, different aspects
      of HBV molecular epidemiology was studied that revealed very interesting results.
      In this study, the clinical significance of HBV genotypes, core promoter and
      precore mutations, possible routes of introduction of HBV genotype C in eastern
      India, the clinical implications of x gene variability, prevalence of the AFB1
      induced p53 gene codon 249 mutation, the transmission potentiality of HBV among
      asymptomatic/inactive or occult HBV carriers and the genetic variability of HBV
      persisting in the PBL was investigated. In this manuscript, the information
      available on the molecular epidemiology of HBV in India has been reviewed and the
      results of studies among the eastern Indian population have been summarised.

PMID- 19099582
TI  - Transgenic increases in seed oil content are associated with the differential
      expression of novel Brassica-specific transcripts.
AB  - BACKGROUND: Seed oil accumulates primarily as triacylglycerol (TAG). While the
      biochemical pathway for TAG biosynthesis is known, its regulation remains
      unclear. Previous research identified microsomal diacylglycerol acyltransferase 1
      (DGAT1, EC 2.3.1.20) as controlling a rate-limiting step in the TAG biosynthesis
      pathway. Of note, overexpression of DGAT1 results in substantial increases in oil
      content and seed size. To further analyze the global consequences of manipulating
      DGAT1 levels during seed development, a concerted transcriptome and metabolome
      analysis of transgenic B. napus prototypes was performed. RESULTS: Using a
      targeted Brassica cDNA microarray, about 200 genes were differentially expressed
      in two independent transgenic lines analyzed. Interestingly, 24-33% of the
      targets showing significant changes have no matching gene in Arabidopsis although
      these represent only 5% of the targets on the microarray. Further analysis of
      some of these novel transcripts indicated that several are inducible by ABA in
      microspore-derived embryos. Of the 200 Arabidopsis genes implicated in lipid
      biology present on the microarray, 36 were found to be differentially regulated
      in DGAT transgenic lines. Furthermore, kinetic reverse transcriptase Polymerase
      Chain Reaction (k-PCR) analysis revealed up-regulation of genes encoding enzymes
      of the Kennedy pathway involved in assembly of TAGs. Hormone profiling indicated
      that levels of auxins and cytokinins varied between transgenic lines and
      untransformed controls, while differences in the pool sizes of ABA and
      catabolites were only observed at later stages of development. CONCLUSION: Our
      results indicate that the increased TAG accumulation observed in transgenic DGAT1
      plants is associated with modest transcriptional and hormonal changes during seed
      development that are not limited to the TAG biosynthesis pathway. These might be
      associated with feedback or feed-forward effects due to altered levels of DGAT1
      activity. The fact that a large fraction of significant amplicons have no
      matching genes in Arabidopsis compromised our ability to draw concrete inferences
      from the data at this stage, but has led to the identification of novel genes of
      potential interest.

PMID- 19099583
TI  - Dacron vs. PTFE as bypass materials in peripheral vascular surgery--systematic
      review and meta-analysis.
AB  - BACKGROUND: In peripheral vascular bypass surgery different synthetic materials
      are available for bypass grafting. It is unclear which of the two commonly used
      materials, polytetrafluoroethylene (PTFE) or polyester (Dacron(R)) grafts, is to
      be preferred. Thus, the aim of this meta-analysis and systematic review was to
      compare the effectiveness of these two prosthetic bypass materials (Dacron and
      PTFE). METHODS: We performed a systematic literature search in MEDLINE, Cochrane
      Library - CENTRAL, EMBASE and other databases for relevant publications in
      English and German published between 1999 and 2008. Only randomized controlled
      trials were considered for inclusion. We assessed the methodological quality by
      means of standardized checklists. Primary patency was used as the main endpoint.
      Random-effect meta-analysis as well as pooling data in life table format was
      performed to combine study results. RESULTS: Nine randomized controlled trials
      (RCT) were included. Two trials showed statistically significant differences in
      primary patency, one favouring Dacron and one favouring PTFE grafts, while 7
      trials did not show statistically significant differences between the two
      materials. Meta-analysis on the comparison of PTFE vs. Dacron grafts yielded no
      differences with regard to primary patency rates (hazard ratio 1.04 (95%
      confidence interval [0.85;1.28]), no significant heterogeneity (p = 0.32, I2 =
      14%)). Similarly, there were no significant differences with regard to secondary
      patency rates. CONCLUSION: Systematic evaluation and meta-analysis of randomized
      controlled trials comparing Dacron and PTFE as bypass materials for peripheral
      vascular surgery showed no evidence of an advantage of one synthetic material
      over the other.

PMID- 19099584
TI  - Use of genome sequence data in the design and testing of SSR markers for
      Phytophthora species.
AB  - BACKGROUND: Microsatellites or single sequence repeats (SSRs) are a powerful
      choice of marker in the study of Phytophthora population biology, epidemiology,
      ecology, genetics and evolution. A strategy was tested in which the publicly
      available unigene datasets extracted from genome sequences of P. infestans, P.
      sojae and P. ramorum were mined for candidate SSR markers that could be applied
      to a wide range of Phytophthora species. RESULTS: A first approach, aimed at the
      identification of polymorphic SSR loci common to many Phytophthora species,
      yielded 171 reliable sequences containing 211 SSRs. Microsatellites were
      identified from 16 target species representing the breadth of diversity across
      the genus. Repeat number ranged from 3 to 16 with most having seven repeats or
      less and four being the most commonly found. Trinucleotide repeats such as
      (AAG)n, (AGG)n and (AGC)n were the most common followed by pentanucleotide,
      tetranucleotide and dinucleotide repeats. A second approach was aimed at the
      identification of useful loci common to a restricted number of species more
      closely related to P. sojae (P. alni, P. cambivora, P. europaea and P.
      fragariae). This analysis yielded 10 trinucleotide and 2 tetranucleotide SSRs
      which were repeated 4, 5 or 6 times. CONCLUSION: Key studies on inter- and intra
      specific variation of selected microsatellites remain. Despite the screening of
      conserved gene coding regions, the sequence diversity between species was high
      and the identification of useful SSR loci applicable to anything other than the
      most closely related pairs of Phytophthora species was challenging. That said,
      many novel SSR loci for species other than the three 'source species' (P.
      infestans, P. sojae and P. ramorum) are reported, offering great potential for
      the investigation of Phytophthora populations. In addition to the presence of
      microsatellites, many of the amplified regions may represent useful molecular
      marker regions for other studies as they are highly variable and easily
      amplifiable from different Phytophthora species.

PMID- 19099585
TI  - Provincial prenatal record revision: a multiple case study of evidence-based
      decision-making at the population-policy level.
AB  - BACKGROUND: There is a significant gap in the knowledge translation literature
      related to how research evidence actually contributes to health care decision
      making. Decisions around what care to provide at the population (rather than
      individual) level are particularly complex, involving considerations such as
      feasibility, cost, and population needs in addition to scientific evidence. One
      example of decision-making at this "population-policy" level involves what
      screening questions and intervention guides to include on standardized provincial
      prenatal records. As mandatory medical reporting forms, prenatal records are
      potentially powerful vehicles for promoting population-wide evidence-based care.
      However, the extent to which Canadian prenatal records reflect best-practice
      recommendations for the assessment of well-known risk factors such as maternal
      smoking and alcohol consumption varies markedly across Canadian provinces and
      territories. The goal of this study is to better understand the interaction of
      contextual factors and research evidence on decision-making at the population
      policy level, by examining the processes by which provincial prenatal records are
      reviewed and revised. METHODS: Guided by Dobrow et al.'s (2004) conceptual model
      for context-based evidence-based decision-making, this study will use a multiple
      case study design with embedded units of analysis to examine contextual factors
      influencing the prenatal record revision process in different Canadian provinces
      and territories. Data will be collected using multiple methods to construct
      detailed case descriptions for each province/territory. Using qualitative data
      analysis techniques, decision-making processes involving prenatal record content
      specifically related to maternal smoking and alcohol use will be compared both
      within and across each case, to identify key contextual factors influencing the
      uptake and application of research evidence by prenatal record review committees.
      All study participants will be required to give written informed consent prior to
      participating in data collection. CONCLUSION: This study will advance knowledge
      in the field of evidence-based decision-making by illustrating the complex
      interaction of contextual factors and evidence on health policy decision-making
      by provincial-level committees. By increasing the transparency of decision-making
      within provincial prenatal record committees, this study will help inform more
      effective strategies for enhancing the integration of best-practice evidence into
      prenatal records.

PMID- 19099586
TI  - Class I histone deacetylases 1, 2 and 3 are highly expressed in renal cell
      cancer.
AB  - BACKGROUND: Enhanced activity of histone deacetylases (HDAC) is associated with
      more aggressive tumour behaviour and tumour progression in various solid tumours.
      The over-expression of these proteins and their known functions in malignant
      neoplasms has led to the development of HDAC inhibitors (HDI) as new anti
      neoplastic drugs. However, little is known about HDAC expression in renal cell
      cancer. METHODS: We investigated the expression of HDAC 1, 2 and 3 in 106 renal
      cell carcinomas and corresponding normal renal tissue by immunohistochemistry on
      tissue micro arrays and correlated expression data with clinico-pathological
      parameters including patient survival. RESULTS: Almost 60% of renal cell
      carcinomas expressed the HDAC isoforms 1 and 2. In contrast, HDAC 3 was only
      detected in 13% of all renal tumours, with particular low expression rates in the
      clear cell subtype. HDAC 3 was significantly higher expressed in pT1/2 tumours in
      comparison to pT3/4 tumours. Expression of class I HDAC isoforms correlated with
      each other and with the proliferative activity of the tumours. We found no
      prognostic value of the expression of any of the HDAC isoforms in this tumour
      entity. CONCLUSION: Class I HDAC isoforms 1 and 2 are highly expressed in renal
      cell cancer, while HDAC 3 shows low, histology dependent expression rates. These
      unexpected differences in the expression patterns suggests alternative regulatory
      mechanisms of class I HDACs in renal cell cancer and should be taken into account
      when trials with isoform selective HDI are being planned. Whether HDAC expression
      in renal cancers is predictive of responsiveness for HDI will have to be tested
      in further studies.

PMID- 19099587
TI  - Local and regional factors influence the structure of treehole metacommunities.
AB  - BACKGROUND: Abiotic and biotic factors in a local habitat may strongly impact the
      community residing within, but spatially structured metacommunities are also
      influenced by regional factors such as immigration and colonization. We used
      three years of monthly treehole census data to evaluate the relative influence of
      local and regional factors on our study system. RESULTS: Every species responded
      to at least one of three local environmental factors measured: water volume, leaf
      litter mass, and presence of a top predator. Several species were affected by
      water volume, and a non-exclusive group of species were influenced by leaf litter
      mass. Relative abundance of Aedes triseriatus was higher in treeholes with higher
      volumes of water, and relative abundances of three out of six other species were
      lower in treeholes with higher volumes of water. Leaf litter mass positively
      affected densities of Aedes triseriatus and relative abundance of several
      dipteran species. The density of the top predator, Toxorhynchites rutilus,
      affected the relative abundance of the two most common species, A. triseriatus
      and Culicoides guttipennis. Treeholes with T. rutilus had an average of two more
      species than treeholes without T. rutilus. We found little evidence of synchrony
      between pairs of treeholes, either spatially or temporally. There were high
      levels of spatial and temporal turnover, and spatial turnover increased with
      distance between patches. CONCLUSION: The strong effects of water volume, leaf
      litter mass, and presence of a top predator, along with the high temporal
      turnover strongly suggest that species presence and density are determined by
      local factors and changes in those factors over time. Both low water volume and
      high predator densities can eliminate populations in local patches, and those
      populations can recolonize patches when rain refills or predators exit treeholes.
      Population densities of the same species were not matched between pairs of
      treeholes, suggesting variation in local factors and limited dispersal. Distance
      effects on spatial turnover also support limitations to dispersal in the
      metacommunity, and we conclude that the weight of evidence favors a strong
      influence of local factors relative to regional factors.

PMID- 19099588
TI  - Phage display-derived inhibitor of the essential cell wall biosynthesis enzyme
      MurF.
AB  - BACKGROUND: To develop antibacterial agents having novel modes of action against
      bacterial cell wall biosynthesis, we targeted the essential MurF enzyme of the
      antibiotic resistant pathogen Pseudomonas aeruginosa. MurF catalyzes the
      formation of a peptide bond between D-Alanyl-D-Alanine (D-Ala-D-Ala) and the cell
      wall precursor uridine 5'-diphosphoryl N-acetylmuramoyl-L-alanyl-D-glutamyl-meso
      diaminopimelic acid (UDP-MurNAc-Ala-Glu-meso-A2pm) with the concomitant
      hydrolysis of ATP to ADP and inorganic phosphate, yielding UDP-N-acetylmuramyl
      pentapeptide. As MurF acts on a dipeptide, we exploited a phage display approach
      to identify peptide ligands having high binding affinities for the enzyme.
      RESULTS: Screening of a phage display 12-mer library using purified P. aeruginosa
      MurF yielded to the identification of the MurFp1 peptide. The MurF substrate UDP
      MurNAc-Ala-Glumeso-A2pm was synthesized and used to develop a sensitive
      spectrophotometric assay to quantify MurF kinetics and inhibition. MurFp1 acted
      as a weak, time-dependent inhibitor of MurF activity but was a potent inhibitor
      when MurF was pre-incubated with UDP-MurNAc-Ala-Glu-meso-A2pm or ATP. In
      contrast, adding the substrate D-Ala-D-Ala during the pre-incubation nullified
      the inhibition. The IC50 value of MurFp1 was evaluated at 250 microM, and the Ki
      was established at 420 microM with respect to the mixed type of inhibition
      against D-Ala-D-Ala. CONCLUSION: MurFp1 exerts its inhibitory action by
      interfering with the utilization of D-Ala-D-Ala by the MurF amide ligase enzyme.
      We propose that MurFp1 exploits UDP-MurNAc-Ala-Glu-meso-A2pm-induced structural
      changes for better interaction with the enzyme. We present the first peptide
      inhibitor of MurF, an enzyme that should be exploited as a target for
      antimicrobial drug development.

PMID- 19099589
TI  - The effect of a low-carbohydrate, ketogenic diet versus a low-glycemic index diet
      on glycemic control in type 2 diabetes mellitus.
AB  - OBJECTIVE: Dietary carbohydrate is the major determinant of postprandial glucose
      levels, and several clinical studies have shown that low-carbohydrate diets
      improve glycemic control. In this study, we tested the hypothesis that a diet
      lower in carbohydrate would lead to greater improvement in glycemic control over
      a 24-week period in patients with obesity and type 2 diabetes mellitus. RESEARCH
      DESIGN AND METHODS: Eighty-four community volunteers with obesity and type 2
      diabetes were randomized to either a low-carbohydrate, ketogenic diet (<20 g of
      carbohydrate daily; LCKD) or a low-glycemic, reduced-calorie diet (500 kcal/day
      deficit from weight maintenance diet; LGID). Both groups received group meetings,
      nutritional supplementation, and an exercise recommendation. The main outcome was
      glycemic control, measured by hemoglobin A1c. RESULTS: Forty-nine (58.3%)
      participants completed the study. Both interventions led to improvements in
      hemoglobin A1c, fasting glucose, fasting insulin, and weight loss. The LCKD group
      had greater improvements in hemoglobin A1c (-1.5% vs. -0.5%, p = 0.03), body
      weight (-11.1 kg vs. -6.9 kg, p = 0.008), and high density lipoprotein
      cholesterol (+5.6 mg/dL vs. 0 mg/dL, p < 0.001) compared to the LGID group.
      Diabetes medications were reduced or eliminated in 95.2% of LCKD vs. 62% of LGID
      participants (p < 0.01). CONCLUSION: Dietary modification led to improvements in
      glycemic control and medication reduction/elimination in motivated volunteers
      with type 2 diabetes. The diet lower in carbohydrate led to greater improvements
      in glycemic control, and more frequent medication reduction/elimination than the
      low glycemic index diet. Lifestyle modification using low carbohydrate
      interventions is effective for improving and reversing type 2 diabetes.

PMID- 19099590
TI  - Genetic polymorphisms of RANTES, IL1-A, MCP-1 and TNF-A genes in patients with
      prostate cancer.
AB  - BACKGROUND: Inflammation has been implicated as an etiological factor in several
      human cancers, including prostate cancer. Allelic variants of the genes involved
      in inflammatory pathways are logical candidates as genetic determinants of
      prostate cancer risk. The purpose of this study was to investigate whether single
      nucleotide polymorphisms of genes that lead to increased levels of pro
      inflammatory cytokines and chemokines are associated with an increased prostate
      cancer risk. METHODS: A case-control study design was used to test the
      association between prostate cancer risk and the polymorphisms TNF-A-308 A/G (rs
      1800629), RANTES-403 G/A (rs 2107538), IL1-A-889 C/T (rs 1800587) and MCP-1 2518
      G/A (rs 1024611) in 296 patients diagnosed with prostate cancer and in 311
      healthy controls from the same area. RESULTS: Diagnosis of prostate cancer was
      significantly associated with TNF-A GA + AA genotype (OR, 1.61; 95% CI, 1.09
      2.64) and RANTES GA + AA genotype (OR, 1.44; 95% CI, 1.09-2.38). A alleles in TNF
      A and RANTES influenced prostate cancer susceptibility and acted independently of
      each other in these subjects. No epistatic effect was found for the combination
      of different polymorphisms studied. Finally, no overall association was found
      between prostate cancer risk and IL1-A or MCP-1 polymorphisms. CONCLUSION: Our
      results and previously published findings on genes associated with innate
      immunity support the hypothesis that polymorphisms in proinflammatory genes may
      be important in prostate cancer development.

PMID- 19099591
TI  - Pathological rate matrices: from primates to pathogens.
AB  - BACKGROUND: Continuous-time Markov models allow flexible, parametrically succinct
      descriptions of sequence divergence. Non-reversible forms of these models are
      more biologically realistic but are challenging to develop. The instantaneous
      rate matrices defined for these models are typically transformed into
      substitution probability matrices using a matrix exponentiation algorithm that
      employs eigendecomposition, but this algorithm has characteristic vulnerabilities
      that lead to significant errors when a rate matrix possesses certain
      'pathological' properties. Here we tested whether pathological rate matrices
      exist in nature, and consider the suitability of different algorithms to their
      computation. RESULTS: We used concatenated protein coding gene alignments from
      microbial genomes, primate genomes and independent intron alignments from primate
      genomes. The Taylor series expansion and eigendecomposition matrix exponentiation
      algorithms were compared to the less widely employed, but more robust, Pade with
      scaling and squaring algorithm for nucleotide, dinucleotide, codon and
      trinucleotide rate matrices. Pathological dinucleotide and trinucleotide matrices
      were evident in the microbial data set, affecting the eigendecomposition and
      Taylor algorithms respectively. Even using a conservative estimate of matrix
      error (occurrence of an invalid probability), both Taylor and eigendecomposition
      algorithms exhibited substantial error rates: ~100% of all exonic trinucleotide
      matrices were pathological to the Taylor algorithm while ~10% of codon positions
      1 and 2 dinucleotide matrices and intronic trinucleotide matrices, and ~30% of
      codon matrices were pathological to eigendecomposition. The majority of Taylor
      algorithm errors derived from occurrence of multiple unobserved states. A small
      number of negative probabilities were detected from the Pade algorithm on
      trinucleotide matrices that were attributable to machine precision. Although the
      Pade algorithm does not facilitate caching of intermediate results, it was up to
      3x faster than eigendecomposition on the same matrices. CONCLUSION: Development
      of robust software for computing non-reversible dinucleotide, codon and higher
      evolutionary models requires implementation of the Pade with scaling and squaring
      algorithm.

PMID- 19099592
TI  - Methylation-sensitive linking libraries enhance gene-enriched sequencing of
      complex genomes and map DNA methylation domains.
AB  - BACKGROUND: Many plant genomes are resistant to whole-genome assembly due to an
      abundance of repetitive sequence, leading to the development of gene-rich
      sequencing techniques. Two such techniques are hypomethylated partial restriction
      (HMPR) and methylation spanning linker libraries (MSLL). These libraries differ
      from other gene-rich datasets in having larger insert sizes, and the MSLL clones
      are designed to provide reads localized to "epigenetic boundaries" where
      methylation begins or ends. RESULTS: A large-scale study in maize generated
      40,299 HMPR sequences and 80,723 MSLL sequences, including MSLL clones exceeding
      100 kb. The paired end reads of MSLL and HMPR clones were shown to be effective
      in linking existing gene-rich sequences into scaffolds. In addition, it was shown
      that the MSLL clones can be used for anchoring these scaffolds to a BAC-based
      physical map. The MSLL end reads effectively identified epigenetic boundaries, as
      indicated by their preferential alignment to regions upstream and downstream from
      annotated genes. The ability to precisely map long stretches of fully methylated
      DNA sequence is a unique outcome of MSLL analysis, and was also shown to provide
      evidence for errors in gene identification. MSLL clones were observed to be
      significantly more repeat-rich in their interiors than in their end reads,
      confirming the correlation between methylation and retroelement content. Both
      MSLL and HMPR reads were found to be substantially gene-enriched, with the SalI
      MSLL libraries being the most highly enriched (31% align to an EST contig), while
      the HMPR clones exhibited exceptional depletion of repetitive DNA (to
      approximately 11%). These two techniques were compared with other gene-enrichment
      methods, and shown to be complementary. CONCLUSION: MSLL technology provides an
      unparalleled approach for mapping the epigenetic status of repetitive blocks and
      for identifying sequences mis-identified as genes. Although the types and natures
      of epigenetic boundaries are barely understood at this time, MSLL technology
      flags both approximate boundaries and methylated genes that deserve additional
      investigation. MSLL and HMPR sequences provide a valuable resource for maize
      genome annotation, and are a uniquely valuable complement to any plant genome
      sequencing project. In order to make these results fully accessible to the
      community, a web display was developed that shows the alignment of MSLL, HMPR,
      and other gene-rich sequences to the BACs; this display is continually updated
      with the latest ESTs and BAC sequences.

PMID- 19099593
TI  - Awareness and implementation of tobacco dependence treatment guidelines in
      Arizona: Healthcare Systems Survey 2000.
AB  - BACKGROUND: This paper presents findings from the Tobacco Control in Arizona
      Healthcare Systems Survey, conducted in 2000. The purpose of the survey was to
      assess the status of Arizona healthcare systems' awareness and implementation of
      tobacco cessation and prevention measures. METHODS: The 20-item survey was
      developed by The University of Arizona HealthCare Partnership in collaboration
      with the Arizona Department of Health Services Bureau of Tobacco Education and
      Prevention. It was mailed to representatives of Arizona's 40 healthcare systems,
      including commercial and Medicare managed care organizations, "managed Medicaid"
      organizations, Veterans Affairs Health Care Systems, and Indian Health Service
      Medical Centers. Thirty-three healthcare systems (83%) completed the survey.
      RESULTS: The majority of healthcare systems reported awareness of at least one
      tobacco cessation and prevention clinical practice guideline, but only one third
      reported full guideline implementation. While a majority covered some form of
      behavioral therapy, less than half reported covering tobacco treatment
      medications. "Managed Medicaid" organizations administered through the Arizona
      Health Care Cost Containment System were significantly less likely to offer
      coverage for behavioral therapy and less likely to cover pharmacotherapy than
      were their non-Medicaid counterparts in managed care, Veterans Affairs Health
      Care Systems and Indian Health Service Medical Centers. CONCLUSION: Arizona
      healthcare system coverage for tobacco cessation in the year 2000 was comparable
      to national survey findings of the same year. The findings that only 10% of
      "Managed Medicaid" organizations covered tobacco treatment medication and were
      significantly less likely to cover behavioral therapy were important given the
      nearly double smoking prevalence among Medicaid patients. Throughout the years of
      the program, the strategic plan of the Arizona Department of Health Services
      Bureau of Tobacco Education and Prevention has included the goal of identifying
      and eliminating tobacco related disparities for special populations, including
      low-income groups. Of importance, in 2008 the Arizona Health Care Cost
      Containment System was authorized to provide tobacco cessation pharmacotherapy as
      a covered benefit for its members.

PMID- 19099594
TI  - A randomized trial on effectiveness of artemether-lumefantrine versus artesunate
      plus amodiaquine for unsupervised treatment of uncomplicated Plasmodium
      falciparum malaria in Ghanaian children.
AB  - BACKGROUND: Numerous trials have demonstrated high efficacy and safety of
      artemisinin-based combination therapy (ACT) under supervised treatment. In
      contrast, effectiveness studies comparing different types of ACT applied
      unsupervised are scarce. The aim of this study was to compare effectiveness,
      tolerability and acceptance of artesunate plus amodiaquine (ASAQ) against that of
      artemether-lumefantrine (AL) in Ghanaian children with uncomplicated Plasmodium
      falciparum malaria. METHODS: A randomized open-label trial was conducted at two
      district hospitals in the Ashanti region, Ghana, an area of intense malaria
      transmission. A total of 246 children under five years of age were randomly
      assigned to either ASAQ (Arsucam) or AL (Coartem). Study participants received
      their first weight-adjusted dose under supervision. After the parent/guardian was
      advised of times and mode of administration the respective three-day treatment
      course was completed unobserved at home. Follow-up visits were performed on days
      3, 7, 14 and 28 to evaluate clinical and parasitological outcomes, adverse
      events, and haematological recovery. Length polymorphisms of variable regions of
      msp1 and msp2 were determined to differentiate recrudescences from reinfections.
      Acceptance levels of both treatment regimens were assessed by means of
      standardized interviews. RESULTS: Adequate clinical and parasitological responses
      after AL and ASAQ treatment were similar (88.3% and 91.7%, respectively).
      Interestingly, more late clinical failures until day 28 occurred in AL-treated
      children than in those who received ASAQ (17.5% and 7.3%, respectively; Hazard
      Ratio 2.41, 95% CI 1.00-5.79, p < 0.05).Haematological recovery and drug
      tolerability were not found to be significantly different in both study arms. The
      acceptance of treatment with ASAQ was higher than that with AL (rank-scores 10.6
      and 10.3, respectively; p < 0.05). CONCLUSION: Unobserved AL and ASAQ treatment
      showed high adequate clinical and parasitological responses, though AL was
      inferior in preventing late clinical failures.

PMID- 19099595
TI  - Breast cancer in Iran: need for greater women awareness of warning signs and
      effective screening methods.
AB  - BACKGROUND: Breast cancer remains an important public health problem. This study
      aimed to investigate about female knowledge of breast cancer and self-reported
      practice of breast self-examination in Iran. METHODS: This was a population-based
      survey carried out in Tehran, Iran. Data were collected via a structured
      questionnaire containing 15 questions on demographic status, history of personal
      and family breast problems, subjective knowledge about breast cancer covering its
      symptoms, the screening methods and practice of breast self-examination (BSE). A
      trained female nurse interviewed each respondent. Analysis included descriptive
      statistics and the Chi-squared test where necessary. RESULTS: A total of 1402
      women were interviewed. The mean age of respondents was 43.4 (SD = 14.4) years;
      most were married (85%), and without any personal (94%) and family history (90%)
      of breast problems. It was found that 64% of the respondents were familiar with
      breast cancer and 61% (n = 851) believed that 'the disease is relatively common
      among women in Iran'. Most women (44%) perceived a painless mass as a breast
      cancer symptom. Overall, 61% of the respondents stated that they knew about
      breast cancer screening programs and most indicated that electronic media
      (television 34% and radio 14%) were their source of information. Only 17% of
      women said that 'they were conducting regular breast self-examination'. The main
      reason for women not doing breast self-examination was due to the fact that they
      did not know how to do it (64%). The findings indicated that performing breast
      self-examination is significantly related to: age, marital status, education,
      knowledge of breast cancer and knowledge about breast cancer screening programs
      (p < 0.05), but not to personal (P = 0.2) and family (P = 0.7) history of breast
      problems. CONCLUSION: This descriptive study provides useful information that
      could be utilized by both researchers and those involved in public health
      programmes. The findings indicated that the women awareness of breast cancer
      warning signs (painless lump, retraction of nipple, and bloody discharge) and
      effective screening methods i.e. clinical examination, and mammography were very
      inadequate. Thus, health education programmes to rectify the lack of women
      awareness is urgently needed. Indeed the focus of primary health care providers
      should be to raise awareness about breast care among women and to encourage them
      to report any unusual changes in their breasts to their family or care
      physicians.

PMID- 19099596
TI  - DDESC: Dragon database for exploration of sodium channels in human.
AB  - BACKGROUND: Sodium channels are heteromultimeric, integral membrane proteins that
      belong to a superfamily of ion channels. The mutations in genes encoding for
      sodium channel proteins have been linked with several inherited genetic disorders
      such as febrile epilepsy, Brugada syndrome, ventricular fibrillation, long QT
      syndrome, or channelopathy associated insensitivity to pain. In spite of these
      significant effects that sodium channel proteins/genes could have on human
      health, there is no publicly available resource focused on sodium channels that
      would support exploration of the sodium channel related information. RESULTS: We
      report here Dragon Database for Exploration of Sodium Channels in Human (DDESC),
      which provides comprehensive information related to sodium channels regarding
      different entities, such as "genes and proteins", "metabolites and enzymes",
      "toxins", "chemicals with pharmacological effects", "disease concepts", "human
      anatomy", "pathways and pathway reactions" and their potential links. DDESC is
      compiled based on text- and data-mining. It allows users to explore potential
      associations between different entities related to sodium channels in human, as
      well as to automatically generate novel hypotheses. CONCLUSION: DDESC is first
      publicly available resource where the information related to sodium channels in
      human can be explored at different levels. This database is freely accessible for
      academic and non-profit users via the worldwide web
      http://apps.sanbi.ac.za/ddesc.

PMID- 19099597
TI  - Antioxidant intervention of smoking-induced lung tumor in mice by vitamin E and
      quercetin.
AB  - BACKGROUND: Epidemiological and in vitro studies suggest that antioxidants such
      as quercetin and vitamin E (VE) can prevent lung tumor caused by smoking;
      however, there is limited evidence from animal studies. METHODS: In the present
      study, Swiss mouse was used to examine the potential of quercetin and VE for
      prevention lung tumor induced by smoking. RESULTS: Our results suggest that the
      incidence of lung tumor and tumor multiplicity were 43.5% and 1.00 +/- 0.29 in
      smoking group; Quercetin has limited effects on lung tumor prevention in this in
      vivo model, as measured by assays for free radical scavenging, reduction of smoke
      induced DNA damage and inhibition of apoptosis. On the other hand, vitamin E
      drastically decreased the incidence of lung tumor and tumor multiplicity which
      were 17.0% and 0.32 +/- 0.16, respectively (p < 0.05); and demonstrated prominent
      antioxidant effects, reduction of DNA damage and decreased cell apoptosis (p <
      0.05). Combined treatment with quercetin and VE in this animal model did not
      demonstrate any effect greater than that due to vitamin E alone. In addition,
      gender differences in the occurrence of smoke induced-lung tumor and antioxidant
      intervention were also observed. CONCLUSION: We conclude that VE might prevent
      lung tumor induced by smoking in Swiss mice.

PMID- 19099598
TI  - Assessment of genetic and functional diversity of phosphate solubilizing
      fluorescent pseudomonads isolated from rhizospheric soil.
AB  - BACKGROUND: Phosphorus is an essential macronutrient for the growth of plants.
      However, in most soils a large portion of phosphorus becomes insoluble and
      therefore, unavailable to plants. Knowledge on biodiversity of phosphate
      solubilizing fluorescent pseudomonads is essential to understand their ecological
      role and their utilization in sustainable agriculture. RESULTS: Of 443
      fluorescent pseudomonad strains tested, 80 strains (18%) showed positive for the
      solubilization of tri-calcium phosphate (Ca3(PO4)2) by the formation of visible
      dissolution halos on Pikovskaya's agar. These phosphate solubilizing strains
      showed high variability in utilizing various carbon sources. Numerical taxonomy
      of the phosphate solubilizing strains based on their carbon source utilization
      profiles resulted into three major phenons at a 0.76 similarity coefficient
      level. Genotypic analyses of strains by BOX (bacterial repetitive BOX element)
      polymerase chain reaction (PCR) resulted into three distinct genomic clusters and
      26 distinct BOX profiles at a 80% similarity level. On the basis of phenotypic
      characterization and 16S rRNA gene phylogenetic analyses strains were identified
      as Pseudomonas aeruginosa, P. mosselii, P. monteilii, P. plecoglossicida, P.
      putida, P. fulva and P. fluorescens. These phosphate solubilizing strains also
      showed the production of plant growth promoting enzymes, hormones and exhibited
      antagonism against phytopathogenic fungi that attack on various crops. Gene
      specific primers have identified the putative antibiotic producing strains. These
      putative strains were grown in fermentation media and production of antibiotics
      was confirmed by thin layer chromatography (TLC) and high performance liquid
      chromatography (HPLC). CONCLUSION: Present study revealed a high degree of
      functional and genetic diversity among the phosphate solubilizing fluorescent
      pseudomonad bacteria. Due to their innate potential of producing an array of
      plant growth promoting enzymes, hormones and antifungal metabolites these
      phosphate solubilizing strains are considered to play a vital role in plant
      growth promotion, disease suppression and subsequent enhancement of yield.

PMID- 19099599
TI  - Conservation and implications of eukaryote transcriptional regulatory regions
      across multiple species.
AB  - BACKGROUND: Increasing evidence shows that whole genomes of eukaryotes are almost
      entirely transcribed into both protein coding genes and an enormous number of non
      protein-coding RNAs (ncRNAs). Therefore, revealing the underlying regulatory
      mechanisms of transcripts becomes imperative. However, for a complete
      understanding of transcriptional regulatory mechanisms, we need to identify the
      regions in which they are found. We will call these transcriptional regulation
      regions, or TRRs, which can be considered functional regions containing a cluster
      of regulatory elements that cooperatively recruit transcriptional factors for
      binding and then regulating the expression of transcripts. RESULTS: We
      constructed a hierarchical stochastic language (HSL) model for the identification
      of core TRRs in yeast based on regulatory cooperation among TRR elements. The HSL
      model trained based on yeast achieved comparable accuracy in predicting TRRs in
      other species, e.g., fruit fly, human, and rice, thus demonstrating the
      conservation of TRRs across species. The HSL model was also used to identify the
      TRRs of genes, such as p53 or OsALYL1, as well as microRNAs. In addition, the
      ENCODE regions were examined by HSL, and TRRs were found to pervasively locate in
      the genomes. CONCLUSION: Our findings indicate that 1) the HSL model can be used
      to accurately predict core TRRs of transcripts across species and 2) identified
      core TRRs by HSL are proper candidates for the further scrutiny of specific
      regulatory elements and mechanisms. Meanwhile, the regulatory activity taking
      place in the abundant numbers of ncRNAs might account for the ubiquitous presence
      of TRRs across the genome. In addition, we also found that the TRRs of protein
      coding genes and ncRNAs are similar in structure, with the latter being more
      conserved than the former.

PMID- 19099600
TI  - Bicaval obstruction complicating right atrial tuberculoma: the diagnostic value
      of cardiovascular MR.
AB  - Cardiac tuberculosis is rare and usually involves the pericardium. Myocardial
      tuberculoma is a very rare occurrence and only a few cases were reported. We
      describe the use of cardiovascular magnetic resonance in the diagnosis of a rare
      case of cardiac tuberculoma involving the right atrium which was complicated by a
      bicaval obstruction. The patient made a remarkable improvement with the anti
      tuberculous treatment. To our knowledge, this complication has never been
      reported in relation to cardiac tuberculoma.

PMID- 19099601
TI  - A clarified position for Solanum lycopersicum var. cerasiforme in the
      evolutionary history of tomatoes (solanaceae).
AB  - BACKGROUND: The natural phenotypic variability present in the germplasm of
      cultivated plants can be linked to molecular polymorphisms using association
      genetics. However it is necessary to consider the genetic structure of the
      germplasm used to avoid false association. The knowledge of genetic structure of
      plant populations can help in inferring plant evolutionary history. In this
      context, we genotyped 360 wild, feral and cultivated accessions with 20 simple
      sequence repeat markers and investigated the extent and structure of the genetic
      variation. The study focused on the red fruited tomato clade involved in the
      domestication of tomato and confirmed the admixture status of cherry tomatoes
      (Solanum lycopersicum var. cerasiforme). We used a nested sample strategy to set
      up core collection maximizing the genetic diversity with a minimum of
      individuals. RESULTS: Molecular diversity was considerably lower in S.
      lycopersicum i.e. the domesticated form. Model-based analysis showed that the 144
      S. lycopersicum var. cerasiforme accessions were structured into two groups: one
      close to the domesticated group and one resulting from the admixture of the S.
      lycopersicum and S. pimpinellifolium genomes. SSR genotyping also indicates that
      domesticated and wild tomatoes have evolved as a species complex with intensive
      level of hybridization. We compiled genotypic and phenotypic data to identify sub
      samples of 8, 24, 32 and 64 cherry tomato accessions that captured most of the
      genetic and morphological diversity present in the entire S. lycopersicum var.
      cerasiforme collection. CONCLUSION: The extent and structure of allelic variation
      is discussed in relation to historical events like domestication and modern
      selection. The potential use of the admixed group of S. lycopersicum var.
      cerasiforme for association genetics studies is also discussed. Nested core
      collections sampled to represent tomato diversity will be useful in diversity
      studies. Molecular and phenotypic variability of these core collections is
      defined. These collections are available for the scientific community and can be
      used as standardized panels for coordinating efforts on identifying novel
      interesting genes and on examining the domestication process in more detail.

PMID- 19099602
TI  - Hospital use of young children in Switzerland: a nation-wide study based on a
      complete survey over 4 years.
AB  - BACKGROUND: Young children are known to be the most frequent hospital users
      compared to older children and young adults. Therefore, they are an important
      population from economic and policy perspectives of health care delivery. In
      Switzerland complete hospitalization discharge records for children [<5 years] of
      four consecutive years [2002-2005] were evaluated in order to analyze variation
      in patterns of hospital use. METHODS: Stationary and outpatient hospitalization
      rates on aggregated ZIP code level were calculated based on census data provided
      by the Swiss federal statistical office (BfS). Thirty-seven hospital service
      areas for children [HSAP] were created with the method of "small area analysis",
      reflecting user-based health markets. Descriptive statistics and general linear
      models were applied to analyze the data. RESULTS: The mean stationary
      hospitalization rate over four years was 66.1 discharges per 1000 children.
      Hospitalizations for respiratory problem are most dominant in young children
      (25.9%) and highest hospitalization rates are associated with geographical
      factors of urban areas and specific language regions. Statistical models yielded
      significant effect estimates for these factors and a significant association
      between ambulatory/outpatient and stationary hospitalization rates. CONCLUSION:
      The utilization-based approach, using HSAP as spatial representation of user
      based health markets, is a valid instrument and allows assessing the supply and
      demand of children's health care services. The study provides for the first time
      estimates for several factors associated with the large variation in the
      utilization and provision of paediatric health care resources in Switzerland.

PMID- 19099603
TI  - Gene expression in early and progression phases of autosomal dominant polycystic
      kidney disease.
AB  - BACKGROUND: Little is known about the genes involved in the initial cyst
      formation and disease progression in autosomal dominant polycystic kidney disease
      (ADPKD); however, such knowledge is necessary to explore therapeutic avenues for
      this common inherited kidney disease. FINDINGS: To uncover the genetic
      determinants and molecular mechanisms of ADPKD, we analyzed 4-point time-series
      DNA microarrays from Pkd1L3/L3 mice to generate high resolution gene expression
      profiles at different stages of disease progression. We found different
      characteristic gene expression signatures in the kidneys of Pkd1L3/L3 mice
      compared to age-matched controls during the initial phase of the disease. By
      postnatal week 1, the Pkd1L3/L3 kidney already had a distinctive gene expression
      pattern different from the corresponding normal controls. CONCLUSION: The genes
      differentially expressed, either induced or repressed, in ADPKD are important in
      immune defense, cell structure and motility, cellular proliferation, apoptosis
      and metabolic processes, and include members of three pathways (Wnt, Notch, and
      BMP) involved in morphogenetic signaling. Further analysis of the gene expression
      profiles from the early stage of cystogenesis to end stage disease identified a
      possible gene network involved in the pathogenesis of ADPKD.

PMID- 19099604
TI  - Analysis of plasmid genes by phylogenetic profiling and visualization of homology
      relationships using Blast2Network.
AB  - BACKGROUND: Phylogenetic methods are well-established bioinformatic tools for
      sequence analysis, allowing to describe the non-independencies of sequences
      because of their common ancestor. However, the evolutionary profiles of bacterial
      genes are often complicated by hidden paralogy and extensive and/or (multiple)
      horizontal gene transfer (HGT) events which make bifurcating trees often
      inappropriate. In this context, plasmid sequences are paradigms of network-like
      relationships characterizing the evolution of prokaryotes. Actually, they can be
      transferred among different organisms allowing the dissemination of novel
      functions, thus playing a pivotal role in prokaryotic evolution. However, the
      study of their evolutionary dynamics is complicated by the absence of universally
      shared genes, a prerequisite for phylogenetic analyses. RESULTS: To overcome such
      limitations we developed a bioinformatic package, named Blast2Network (B2N),
      allowing the automatic phylogenetic profiling and the visualization of homology
      relationships in a large number of plasmid sequences. The software was applied to
      the study of 47 completely sequenced plasmids coming from Escherichia, Salmonella
      and Shigella spps. CONCLUSION: The tools implemented by B2N allow to describe and
      visualize in a new way some of the evolutionary features of plasmid molecules of
      Enterobacteriaceae; in particular it helped to shed some light on the complex
      history of Escherichia, Salmonella and Shigella plasmids and to focus on possible
      roles of unannotated proteins.The proposed methodology is general enough to be
      used for comparative genomic analyses of bacteria.

PMID- 19099605
TI  - Squamous cell carcinoma of the breast: a case report.
AB  - BACKGROUND: Squamous cells are normally not found inside the breast, so a primary
      squamous cell carcinoma of the breast is an exceptional phenomenon. There is a
      possible explanation for these findings. CASE PRESENTATION: A 72-year-old woman
      presented with a breast abnormality suspected for breast carcinoma. After the
      operation the pathological examination revealed a primary squamous cell carcinoma
      of the breast. CONCLUSION: The presentation of squamous cell carcinoma could be
      similar to that of an adenocarcinoma. However, a squamous cell carcinoma of the
      breast could also develop from a complicated breast cyst or abscess. Therefore,
      pathological examination of these apparent benign abnormalities is mandatory.

PMID- 19099606
TI  - The primary care amplification model: taking the best of primary care forward.
AB  - BACKGROUND: Primary care internationally is approaching a new paradigm. The
      change agenda implicit in this threatens to de-stabilise and challenge
      established general practice and primary care. DISCUSSION: The Primary Care
      Amplification Model offers a means to harness the change agenda by 'amplifying'
      the strengths of established general practices around a 'beacon' practice.
      CONCLUSION: Such 'beacon' practices can provide a mustering point for an expanded
      scope of practice for primary care, integrated primary/secondary service
      delivery, interprofessional learning, relevant local clinical research, and a
      focus on local service innovation, enhancing rather than fragmenting the
      collective capacity of existing primary care.

PMID- 19099607
TI  - LIM only 4 is overexpressed in late stage pancreas cancer.
AB  - BACKGROUND: LIM-only 4 (LMO4), a member of the LIM-only (LMO) subfamily of LIM
      domain-containing transcription factors, was initially reported to have an
      oncogenic role in breast cancer. We hypothesized that LMO4 may be related to
      pancreatic carcinogenesis as it is in breast carcinogenesis. If so, this could
      result in a better understanding of tumorigenesis in pancreatic cancer. METHODS:
      We measured LMO4 mRNA levels in cultured cells, pancreatic bulk tissues and
      microdissected target cells (normal ductal cells; pancreatic intraepithelial
      neoplasia-1B [PanIN-1B] cells; PanIN-2 cells; invasive ductal carcinoma [IDC]
      cells; intraductal papillary-mucinous adenoma [IPMA] cells; IPM borderline [IPMB]
      cells; and invasive and non-invasive IPM carcinoma [IPMC]) by quantitative real
      time reverse transcription-polymerase chain reaction (qRT-PCR). RESULTS: 9 of 14
      pancreatic cancer cell lines expressed higher levels of LMO4 mRNA than did the
      human pancreatic ductal epithelial cell line (HPDE). In bulk tissue samples,
      expression of LMO4 was higher in pancreatic carcinoma than in intraductal
      papillary-mucinous neoplasm (IPMN) or non-neoplastic pancreas (p < 0.0001 for
      both). We carried out microdissection-based analyses. IDC cells expressed
      significantly higher levels of LMO4 than did normal ductal epithelia or PanIN-1B
      cells (p < 0.001 for both) or PanIN-2 cells (p = 0.014). IPMC cells expressed
      significantly higher levels of LMO4 than did normal ductal epithelia (p < 0.001),
      IPMA (p < 0.001) and IPMB cells (p = 0.003). CONCLUSION: Pancreatic carcinomas
      (both IDC and IPMC) expressed significantly higher levels of LMO4 mRNA than did
      normal ductal epithelia, PanIN-1B, PanIN-2, IPMA and IPMB. These results
      suggested that LMO4 is overexpressed at late stages in carcinogenesis of
      pancreatic cancer.

PMID- 19099608
TI  - Plant growth promotion and Penicillium citrinum.
AB  - BACKGROUND: Endophytic fungi are known plant symbionts. They produce a variety of
      beneficial metabolites for plant growth and survival, as well as defend their
      hosts from attack of certain pathogens. Coastal dunes are nutrient deficient and
      offer harsh, saline environment for the existing flora and fauna. Endophytic
      fungi may play an important role in plant survival by enhancing nutrient uptake
      and producing growth-promoting metabolites such as gibberellins and auxins. We
      screened roots of Ixeris repenes (L.) A. Gray, a common dune plant, for the
      isolation of gibberellin secreting endophytic fungi. RESULTS: We isolated 15
      endophytic fungi from the roots of Ixeris repenes and screened them for growth
      promoting secondary metabolites. The fungal isolate IR-3-3 gave maximum plant
      growth when applied to waito-c rice and Atriplex gemelinii seedlings. Analysis of
      the culture filtrate of IR-3-3 showed the presence of physiologically active
      gibberellins, GA1, GA3, GA4 and GA7 (1.95 ng/ml, 3.83 ng/ml, 6.03 ng/ml and 2.35
      ng/ml, respectively) along with other physiologically inactive GA5, GA9, GA12,
      GA15, GA19, GA20 and, GA24. The plant growth promotion and gibberellin producing
      capacity of IR-3-3 was much higher than the wild type Gibberella fujikuroi, which
      was taken as control during present study. GA5, a precursor of bioactive GA3 was
      reported for the first time in fungi. The fungal isolate IR-3-3 was identified as
      a new strain of Penicillium citrinum (named as P. citrinum KACC43900) through
      phylogenetic analysis of 18S rDNA sequence. CONCLUSION: Isolation of new strain
      of Penicillium citrinum from the sand dune flora is interesting as information on
      the presence of Pencillium species in coastal sand dunes is limited. The plant
      growth promoting ability of this fungal strain may help in conservation and
      revegetation of the rapidly eroding sand dune flora. Penicillium citrinum is
      already known for producing mycotoxin citrinin and cellulose digesting enzymes
      like cellulase and endoglucanase, as well as xylulase. Gibberellins producing
      ability of this fungus and the discovery about the presence of GA5 will open new
      aspects of research and investigations.

PMID- 19099609
TI  - GeneTrailExpress: a web-based pipeline for the statistical evaluation of
      microarray experiments.
AB  - BACKGROUND: High-throughput methods that allow for measuring the expression of
      thousands of genes or proteins simultaneously have opened new avenues for
      studying biochemical processes. While the noisiness of the data necessitates an
      extensive pre-processing of the raw data, the high dimensionality requires
      effective statistical analysis methods that facilitate the identification of
      crucial biological features and relations. For these reasons, the evaluation and
      interpretation of expression data is a complex, labor-intensive multi-step
      process. While a variety of tools for normalizing, analysing, or visualizing
      expression profiles has been developed in the last years, most of these tools
      offer only functionality for accomplishing certain steps of the evaluation
      pipeline. RESULTS: Here, we present a web-based toolbox that provides rich
      functionality for all steps of the evaluation pipeline. Our tool GeneTrailExpress
      offers besides standard normalization procedures powerful statistical analysis
      methods for studying a large variety of biological categories and pathways.
      Furthermore, an integrated graph visualization tool, BiNA, enables the user to
      draw the relevant biological pathways applying cutting-edge graph-layout
      algorithms. CONCLUSION: Our gene expression toolbox with its interactive
      visualization of the pathways and the expression values projected onto the nodes
      will simplify the analysis and interpretation of biochemical pathways
      considerably.

PMID- 19099610
TI  - Comparative assessment of passive surveillance in disease-free and endemic
      situation: example of Brucella melitensis surveillance in Switzerland and in
      Bosnia and Herzegovina.
AB  - BACKGROUND: Globalization and subsequent growth in international trade in animals
      and animal products has increased the importance of international disease
      reporting. Efficient and reliable surveillance systems are needed in order to
      document the disease status of a population at a given time. In this context,
      passive surveillance plays an important role in early warning systems. However,
      it is not yet routinely integrated in the assessment of disease surveillance
      systems because different factors like the disease awareness (DA) of people
      reporting suspect cases influence the detection performance of passive
      surveillance. In this paper, we used scenario tree methodology in order to
      evaluate and compare the quality and benefit of abortion testing (ABT) for
      Brucella melitensis (Bm) between the disease free situation in Switzerland (CH)
      and a hypothetical disease free situation in Bosnia and Herzegovina (BH), taking
      into account DA levels assumed for the current endemic situation in BH. RESULTS:
      The structure and input parameters of the scenario tree were identical for CH and
      BH with the exception of population data in small ruminants and the DA in farmers
      and veterinarians. The sensitivity analysis of the stochastic scenario tree model
      showed that the small ruminant population structure and the DA of farmers were
      important influential parameters with regard to the unit sensitivity of ABT in
      both CH and BH. The DA of both farmers and veterinarians was assumed to be higher
      in BH than in CH due to the current endemic situation in BH. Although the same DA
      cannot necessarily be assumed for the modelled hypothetical disease free
      situation as for the actual endemic situation, it shows the importance of the
      higher vigilance of people reporting suspect cases on the probability that an
      average unit processed in the ABT-component would test positive. CONCLUSION: The
      actual sensitivity of passive surveillance approaches heavily depends on the
      context in which they are applied. Scenario tree modelling allows for the
      evaluation of such passive surveillance system components under assumed disease
      free situation. Despite data gaps, this is a real opportunity to compare
      different situations and to explore consequences of changes that could be made.

PMID- 19099611
TI  - Gross and microscopic hematuria: guidelines for obstetricians and gynecologists.
AB  - Although gross hematuria is a relatively uncommon condition in general obstetrics
      and gynecology practice, microscopic hematuria is a common incidental finding
      during routine antepartum or gynecologic office visits. The proper evaluation and
      treatment options are understudied in females. In fact, work-up of females is
      controversial, and no consensus guidelines exist at this time. Pregnancy
      increases the number of potential diagnoses. The majority of published literature
      on hematuria in pregnancy is in the form of case reports, and esoteric diagnoses
      are disproportionately represented. The purpose of this review is to summarize
      existing literature regarding the evaluation, differential diagnosis, and
      treatment of hematuria in women, with special emphasis on pregnancy and the
      diagnosis and treatment of microscopic hematuria.

PMID- 19099612
TI  - Sonographic fetal sex determination.
AB  - Although sonographic fetal sex determination is feasible in most pregnancies, in
      some cases, it may pose difficulties. An attempt to determine the fetal sex
      should not be made before 12-weeks' gestation because this early, it is
      relatively inaccurate. After 13 weeks, it is accurate in 99% to 100% of cases
      without malformed external genitalia. Sonographic fetal sex determination in the
      late second trimester is based on direct visualization of the external genitalia,
      whereas in the late first and early second trimester, it is based mainly on the
      direction of the genital tubercle (the "sagittal sign"): downward direction of
      the genital tubercle indicates a female fetus and upward direction a male fetus.
      Other sonographic landmarks, such as the fetal scrotum, the midline raphe of the
      penis, the labial lines, the uterus, the descended testis, and the direction and
      origin of the fetal micturition jet in males may contribute to the correct
      determination of fetal sex. Inaccurate fetal sex determination may occur when the
      external genitalia are malformed. Three-dimensional ultrasound, although of
      generally limited diagnostic value for fetal sex determination, may aid in better
      definition of congenital malformations of the external genitalia.

PMID- 19099613
TI  - Physiological changes associated with the menstrual cycle: a review.
AB  - The cyclic hormonal changes that regulate the menstrual cycle are a significant
      biological influence on the female body, one with both physical and emotional
      ramifications. Menstruation is governed by tightly orchestrated changes in the
      levels of ovarian estrogen and progesterone, which produce varying responses in
      diverse tissues and organs. The skin, the largest organ in the body, is replete
      with estrogen receptors (in both dermis and epidermis) and to a lesser extent,
      progesterone receptors. Cyclically fluctuating levels of estrogen and
      progesterone influence numerous characteristics of the epidermis, including skin
      surface lipid secretion and sebum production, skin thickness, fat deposition,
      skin hydration, and barrier function. Dermal collagen content, which contributes
      to skin elasticity and resistance to wrinkling, is also influenced.
      Interestingly, estrogen levels also influence skin pigmentation and UV
      susceptibility, as well as resident microflora. In addition, changing hormone
      levels across the menstrual cycle produce measurable variations in immune
      function and disease susceptibility. An understanding of the profound influence
      that fluctuating estrogen and progesterone levels have on the biological
      responses of the premenopausal adult woman is critical to optimizing the efficacy
      of medical therapies in this population.

PMID- 19099614
TI  - Product development partnerships (PDPs) for neglected diseases: considerations on
      governance.

PMID- 19099615
TI  - Patient choice and access to primary physician services in Norway.
AB  - Quasi-markets have become fashionable within health care. This is also the case
      in Norway where primary physician services are organized as a quasi-market.
      Physicians compete for patients, and patients can choose another physician if
      they are not satisfied with the physician they have. This is meant to provide
      incentives for physicians to provide services that are both efficient and of high
      quality. One condition that is necessary in order for such a market to function
      is that there is excess supply to ensure that patients have a real opportunity
      for choice. In this study we investigated the influence of excess supply on
      patient access and the mobility of patients between primary physicians in Norway.
      The analyses were performed on data from two comprehensive national surveys.
      Access to physicians is better for physicians who have spare capacity than for
      physicians who have a lack of capacity. Patients take advantage of their
      possibilities for choice. They move from physicians who have too little capacity
      to physicians who have spare capacity. Patient choice means that patients are not
      'stuck' with physicians who have too little capacity to provide adequate services
      for their patients. The results show that quasi-markets can ensure good access to
      primary physician services, but this presupposes that there is enough spare
      capacity to provide patients with a real choice of physician.

PMID- 19099616
TI  - Policy choice or economic fundamentals: what drives the public-private health
      expenditure balance in Canada?
AB  - The public share of Canadian total health expenditure declined between 1975 and
      2005 but categories such as physicians stayed constant while drugs, other
      institutions, and capital spending saw increases. Regressions find the key
      determinants of the public share to be: the relative price of health care, per
      capita income, federal transfers, proportion of population over age 65,
      provincial dummy variables, political parties, the onset of the Canada Health Act
      and the Canada Health and Social Transfer (CHST), and a time trend invoking
      technological change. Increasing income inequality is not a factor eroding the
      public share. Moreover, provinces governed by center-left parties are associated
      with lower public shares in the physician and other health professional
      categories. The significance of variables like the Canada Health and Social
      Transfer, the Canada Health Act and provincial differences suggest the increase
      in the private share of health spending since 1975 is partly the result of policy
      choices. As the public share has only declined from approximately 76% to 70% over
      30 years, it appears the shift towards private care is one of marginal
      increments. Canadians remain in conflict over their health care system as they
      appear willing to tolerate only marginal accretions in the overall private share
      of health spending but accept larger changes across health expenditure categories
      and provincial systems.

PMID- 19099617
TI  - Small area variations and welfare loss in the use of outpatient antibiotics.
AB  - This article seeks to explain local variations in the use of antibiotics in the
      community and to assess the welfare loss due to heterogeneous attitudes towards
      the risk of bacterial resistance. Quarterly data on antibiotic sales from 240
      small areas in Switzerland over the course of one year are used. An econometric
      ad-hoc model with spatial lags is proposed in which the demand for antibiotics
      varies according to the socioeconomic characteristics of the population, the
      incidence of infections, antibiotic price and local health care supply. Using
      residual variations we then evaluate the welfare loss due to varying antibiotic
      prescription styles. Significant differences are observed in the per capita
      antibiotic consumption across local areas. Individual income, the demographic
      structure of the population, physician density and the price of drugs are all
      relevant determinants. We estimate that unexplained variations may account for
      12% of the total antibiotic spending in the community, thus leading to a Euro 6.8
      ml loss per year. Understanding the determinants of variations in outpatient
      antibiotic consumption may help to design more effective policies to counter the
      threat of bacterial resistance. Our estimate of the welfare loss due to
      heterogeneous attitudes towards antibiotic treatment is comparable to the
      expected cost of implementing measures to improve the dissemination of
      information on bacterial resistance among patients and doctors.

PMID- 19099618
TI  - The legal framework for health care quality assurance in Germany.
AB  - Like most industrialized countries, Germany's health care system is facing two
      major challenges. The first is to find a sustainable financing system for
      increasing health care expenditures. The second is to ensure - and improve - the
      quality of care provided. This article describes the status quo in quality
      assurance in Germany and analyses the changes introduced into the SHI (Statutory
      Health Insurance) system with the Modernization Act of 2004. First, a theoretical
      framework for quality assurance that is consistent with the logic of the German
      social market economy is outlined. The analysis then describes new actors and
      their duties in the field of quality assurance, highlighting improvements in
      regulation and the regulatory instruments applied. Although the strategy for
      quality assurance is still dominated by regulation and corporatist bodies, the
      latest reform acts of 2004 and 2007 focus on more and better information about
      the quality of services provided - an important prerequisite for more competitive
      elements in the German health care system.

PMID- 19099619
TI  - Towards an alternative economics of health care.
AB  - It is argued here that an economics centred on subjective utility-maximization is
      unsuitable for the analysis and policy grounding of health care provision. To
      some extent, the peculiarities of health care have been recognized by mainstream
      health economists, who sometimes abandon Paretian welfare considerations to focus
      on needs instead. This article examines important peculiarities of health care
      that are relatively neglected in the literature. Some of these concern health
      care needs: while health itself is a universal need, needs for health care
      provision are largely involuntary, varied, and idiosyncratic. These issues have
      important consequences for the planning of health care systems and the extent of
      transaction costs in any market-based system. These factors, combined with the
      inherent dynamism of modern health care needs and capabilities, create an opening
      for alternative approaches to health care economics.

PMID- 19099620
TI  - Global health challenges in the pharmaceutical world.

PMID- 19099621
TI  - [Latent infection of human herpes virus in hematopoietic system].
AB  - Up to date, eight types of human herpes viruses have been identified, all of
      which are ubiquitous, and usually establish latent infection in the host after
      primary infection. Since most of the herpes viruses are maintained in an
      asymptomatic form, they are often neglected. However, under some circumstances,
      these herpes viruses can cause fatal or severe diseases. Furthermore, the
      association of herpes viruses with hematopoietic malignancies is attracting
      researchers' attention. With the extensive development of hematopoietic stem cell
      and organ transplantation, reports regarding transplantation failure and
      complication caused by infection of human herpes virus has been increasing.
      Cytokine storm was firstly suggested as the mechanism of graft-versus-host
      diseases. In recent years, which has also been applied in the pathogenesis
      research of inflammation, and is supposed to play an important role in severe
      virus infection. In this paper, through discussing the possible role of latent
      infection of human herpes virus in the failure or complication of bone marrow or
      hematopoietic stem cell transplantation, and in refractory leukemia, the function
      and significance of latent infection of human herpes virus and the cytokine storm
      it caused were investigated.

PMID- 19099622
TI  - [Aberrations of chromosome 5 in myeloid malignancies with complex chromosome
      abnormalities].
AB  - This study was aimed to investigate the chromosome 5 abnormalities in complex
      chromosome aberrations (CCAs) in myeloid malignancies, chromosome aberrations of
      68 cases of myeloid malignancies with CCAs were analysed. The 68 cases included
      22 cases of acute myeloblastic leukemia (AML), 32 cases of chronic myeloid
      leukemia (CML) and 14 cases of myelodysplastic syndrome (MDS). The results showed
      that the complex chromosome abnormalities were found in all chromosomes of 68
      cases, but the incidence of chromosome 5 abnormality was higher (38.2%, 26/68),
      including 45.5% (10/22) in AML, 15.6% (5/32) in CML and 78.6% (11/14) in MDS. The
      most common aberrations in chromosome 5 were unbalanced translocations. The
      aberrations of chromosome 5 and chromosome 17 were confirmed simultaneously in 11
      cases, the aberrations of chromosome 5 and chromosome 7 were confirmed
      simultaneously in 9 cases. It is concluded that the aberration of chromosome 5 is
      common in myeloid malignancies, and presents unbalanced translocation.
      Aberrations of chromosome 5 often accompany with aberrations of chromosome 7 or
      17.

PMID- 19099623
TI  - [Detection of chromosome 13 deletion in plasma cell leukemia by dual-color
      fluorescence in situ hybridization].
AB  - This study was aimed to investigate the deletion features of chromosome 13 in
      plasma cell leukemia (PCL) and its relationship with clinical features. The dual
      color fluorescence in situ hybridization (FISH) with two different specific
      probes for the regions containing 13q14 and 13q31 was used to delet the
      chromosome in 21 patients with PCL. The results showed that 13 (61.9%) out of 21
      PCL had 13q14 deletion. The number of 13q14 deletion cells ranged from 52% to
      98%. 12 patients (57.4%) had 13q31 deletion. The number of cells with 13q31
      deletion ranged from 50% to 98%. Out of 13 cases with (13q14) deletion, 12 cases
      had (13q31) deletion, but only 1 out of 12 cases was negative. It is concluded
      that chromosome 13 deletion may be involved in initiation of a subset of PCL, and
      the region of loss at chromosome 13 locates between 13q14 and 13q31 in PCL. FISH
      is a more rapid, exact and sensitive technique in analysis of chromosome 13
      deletion in PCL.

PMID- 19099624
TI  - [Expression of erythropoietin receptor in leukemia cells and relation of
      erythropoietin level with leukemic anemia].
AB  - This study was purposed to investigate the expression of erythropoietin receptor
      (EPOR) in leukemic cells and the relationship of serum erythropoietin level with
      anemia in acute leukemia patients, so as to provide a new theoretical basis for
      the cytokine therapy in acute leukemia with anemia. The EPOR in 30 AL patients
      was detected by using reverse transcription polymerase chain reaction (RT-PCR),
      the level of serum erythropoietin was detected by chemiluminescence analysis, the
      hemoglobin level was assayed by automatic blood counting instrument. The results
      indicated that EPOR was expressed in 18 out of 30 AL patients, the expression
      rate of EPOR in AL patients was 60%, however, but the EPOR expression rate in AML
      was 61.9% (13/21) and 55.6% (5/9) in ALL, the EPOR expression rate was no
      significant difference between AML and ALL. The EPOR expression rate was
      significantly lower than that in control group (86.7%) (p<0.05). The relative
      level of EPOR expression in AML was higher than that in ALL (p<0.05), the average
      level of EPOR expression in AL was significantly lower than that in control group
      (p<0.01). The level of sEPO in 30 AL patients was significantly higher than that
      in control group (p<0.01), and there was negative correlation between the levels
      of sEPO and Hb (p<0.01). It is concluded that the EPOR is expressed in cells of
      AL, but the expressive level is low. The EPOR expression rate shows no
      significant difference between AML and ALL. The mechanism of negative feedback to
      anemia in acute leukemia is intact. Anemia of acute leukemia is not completely
      associated with inadequate erythropoietin production and relates to hemopoiesis
      defect that considered as the main reason. Recombinant human erythropoietin is
      widely used in treatment of anemia caused by acute leukemia. Whether the
      treatment with rh-EPO for acute leukemia with anemia will enhance the
      proliferation of leukemia cells, this problem should be explored further.

PMID- 19099625
TI  - [Expression of SALL4 and BMI-1 mRNA in acute leukemia].
AB  - This study was aimed to investigate the expression of SALL4 and BMI-1 mRNA in
      acute leukemia (AL) and its clinical significance. mRNA expression levels of
      SALL4 and BMI-1 in 62 AL patients and 10 controls were measured by semi
      quantitative reverse transcription-polymerase chain reaction (RT-PCR). The
      results showed that (1) the expression of SALL4 mRNA were up-regulated in AL
      (except M3 and T-ALL), and the expression of of SALL4 mRNA in AML was
      significantly higher than that in B-ALL (p<0.05); expression was negative in 9
      out of 10 controls, and expression level of SALL4 mRNA in one case was low; (2)
      the expression of SALL4 in de novo AL was higher than that in controls, which
      significantly decreased at complete remission (CR). The difference between CR
      group and de novo group was statistically significant (p<0.05). In relapsed
      patients, the expression of SALL4 increased, slightly higher than that in de novo
      AL group (p>0.05); (3) the expression pattern of BMI-1 was the same to that of
      SALL4 except the up-regulation in M3, and the expression of BMI-1 was positively
      correlated with that of SALL4 in acute leukemia (r=0.684, p<0.01). It is
      concluded that SALL4 and BMI-1 expressions are up-regulated significantly in
      acute leukemia, which may contribute to the development of leukemia, thus become
      an important index for evaluation of development, relapse and prognosis in acute
      leukemia.

PMID- 19099626
TI  - [Effects of PML-RARalpha on cAMP-induced AML cell differentiation].
AB  - To explore the molecular mechanisms of acute promyelocytic leukemia cell
      differentiation induced by cAMP combined with low-dose As2O3, the PR9 cell line,
      which was stably transfected by PML-RARa fusion gene, was used as in vitro model.
      The effects of PML-RARa on cAMP-induced AML cell differentiation were evaluated
      according to cell growth, cell morphology, cell surface antigen as well as
      luciferase reporter gene assay, in the cells before and after the treatment with
      cAMP and/or As2O3. The results showed that cAMP alone could slightly increase the
      expression of CD11b in the PR9 cells expressing the PML-RARa fusion protein, but
      could not induce these cells to differentiate. The cells presented the terminal
      differentiation morphology and significantly increased CD11b expression only
      under the treatment of cAMP combined with As2O3. In addition, PML-RARa had strong
      inhibitory activity on the transcription of the reporter gene containing cAMP
      response elements. In conclusions, the PML-RARa fusion protein could dramatically
      block the signaling pathway of cAMP during the AML cell differentiation.

PMID- 19099627
TI  - [Mechanism of CAG regimen eliminating T-cell acute lymphoblastic leukemia A3 cell
      line].
AB  - The purpose of this study was to explore the mechanism of CAG regimen eliminating
      T-cell acute lymphoblastic leukemia (T-ALL) A3 cell line and evaluate the role of
      G-CSF/G-CSFR system in this process. The expression levels of G-CSFR on the A3
      cell membrane were detected by flow cytometry. Cell cycle changes of A3 cells
      treated with different concentrations of G-CSF for 48 hours were examined by
      propidium iodide staining method. The inhibition and apoptosis rates of A3 cells
      treated with various combinations of G-CSF, cytarabine (Ara-C), aclarubicin (ACR)
      were analyzed by Cell Counting Kit and AnnexinV Kit, respectively. The results
      indicated that the expression level of G-CSFR on A3 cells was 94.2%. The
      proportion of A3 cells in S-phase rose concomitantly with the increasing of G-CSF
      concentrations within 0-20 ng/ml. After incubation with Ara-C and G-CSF for 48
      hours, A3 cells were inhibited more obviously compared with incubation with Ara-C
      alone (p<0.05, Ara-C 10(-5) mol/L and 10(-6) mol/L). After incubation with Ara-C,
      ACR and G-CSF for 48 hours, the apoptotic rate of A3 cells was much more than
      that after incubation with Ara-C and ACR. It is concluded that the expression
      level of G-CSFR on A3 cells is high, G-CSF/G-CSFR system has a synergetic effect
      on eliminating A3 cells when administrated simultaneously with chemical agents.
      This effect is caused through driving more cells from G0 phase into S phase,
      increasing sensitivity of A3 cells to chemical drugs and inducing cell apoptosis
      which may be one of the mechanisms of CAG regimen eliminating A3 cells.

PMID- 19099628
TI  - [Enhancement of reversing drug resistance of K562/A02 cells to adriamycin by
      ultrasound-induced cavitation].
AB  - This study was aimed to investigate the effects of low frequency and power
      ultrasound combined with adriamycin on apoptosis of drug-resistant leukemia cell
      line K562/A02 in vitro, to find out the parameters of optimal exposure, and to
      explore the possible mechanism reversing drug-resistance of K562/A02 cells. The
      K562/A02 cells in logarithmic growth phase were used in experiments. The
      experiments were divided into 4 groups: group control, group adriamycin (A02)
      alone, group ultrasound (US) alone and group A02+US. The trypan blue dye
      exclusion test and MTT assay were used to determine the cell viability; Wright's
      staining was used to detect the apoptosis; the flow cytometry was used to analyze
      the drug concentration, and the scanning electron microscopy was used to observe
      the changes of cell surface. The results showed that the significant differences
      in cell viability, intracellular adriamycin concentration and changes of cell
      membrane were found between ultrasound-treated and untreated cells in the
      presence of various concentration of adriamycin. The exposure to ultrasound at 20
      kHZ, 0.25 W/cm2 for 60 seconds could obviously decrease LC50 of adriamycin to
      K562/A02 cells, while the exposure to ultrasound at 20 kHZ, 0.05 W/cm2 for 60
      seconds could kill K562/A02 cells at once. After being treated by low frequency
      ultrasound, the small holes with diameter about 1-2 microm in the cell surface
      appeared. The ultrasound increased the adriamycin concentration in the cells,
      accelerated the formation of apoptotic bodies, and promoted apoptosis of
      adriamycin-resistant cells. It is concluded that the ultrasound at optimal
      parameters enhances inhibitory effect of adriamycin on drug-resistant cell line,
      thereby reverses drug-resistance of drug-resistant cell line through sound-hole
      effect in tumor cells resulting from ultrasound induced cavitation.

PMID- 19099629
TI  - [Synergistic effects of VPA and As2O3 on Molt-4 cells in vitro and its possible
      mechanisms].
AB  - This study was purposed to investigate the synergistic effects of sodium
      valproate (VPA) and As2O3 on the proliferation of Molt-4 cells in vitro and its
      possible mechanisms. Cell viability and growth curve were assessed by the MTT
      assay. The synergistic activity in combination of 2 drugs was determined by the Q
      format. The expression levels of p15, DNA methyltransferase 1 (DNMT-1), DNMT3A
      and DNMT 3B mRNA were detected by RT-PCR and the methylation level was detected
      by hn-MSPCR. The results indicated that the VPA and As2O3 both inhibited
      proliferation of Molt-4 cells. The combination of two drugs showed an additive
      effect (values of Q were>or=0.85). The inhibitory rate in combination of 5 mmol/L
      of VPA with 10 micromol/L of As2O3 was (70.31+/-2.54)%. The p15 gene in Molt-4
      cell line failed to express due to its hypermethylation. The level of p15 gene
      mRNA expression increased significantly after exposure to VPA in combination with
      As2O3 for 48 h. As compared with control group, the expression of DNMT-1 was down
      regulated in a dose-dependent manner, whereas DNMT3A had no significant
      differences from the control. The level of expression of DNMT3B seemed to
      decrease at 10 mmol/L concentration. There were significant differences between
      the combination of the two drugs and the control group. The gray value of
      methylated bands decreased after the treatment of VPA alone and in combination
      with As2O3 in a dose-dependent manner. It is concluded that VPA induces
      demethylation of p15 INK4B gene by inhibiting the DNMT-1 and DNMT3B gene
      activities, which up-regulates the p15 gene, recovers its activity. The
      combination of VPA with As2O3 has the synergistic additive effect on the
      inhibition of cell viability, so that VPA can reduce the side effect of As2O3 on
      liver function, which would be verified in the clinical practice.

PMID- 19099630
TI  - [Effect of psoralen plus longwave UVA inducing HL-60 cells apoptosis].
AB  - The aim of this study was to investigate the effects of the traditional Chinese
      medicine psoralen (PSO) plus long wave ultraviolet A (PUVA) on apoptosis in HL-60
      leukemia cells and its mechanism. The effect of PUVA on HL-60 cell growth was
      assayed by MTT method and the changes of ultrastructure of cells were observed by
      electron microscopy. The apoptosis ratios, changes of mitochondrial membrane
      potential, expression of Fas and FasL protein and Fas and FasL mRNA were detected
      by FCM and fluorescent quantitation RT-PCR respectively. The expression of
      Caspase 8 and Caspase 3 protein were detected by immunocytochemistry (ICC). The
      results showed that the growth of HL-60 cells were inhibited by PUVA in time-and
      concentration-dependent manner through inducing cell apoptosis. When the
      irradiation time of long wave ultraviolet A lasted 15 minutes and the
      concentration of PSO was 80 microg/ml, the inhibition of HL-60 cell proliferation
      and apoptosis ratios reached the peak. There were obvious apoptotic
      ultrastructure changes and decrease of mitochondrial membrane potential in HL-60
      cells after treatment with PUVA. The expression of Fas mRAN increased and
      expression of FasL mRNA decreased after treating with PUVA for 4 hours, and the
      same results of Fas, FasL expression on protein level were obtained also after
      treating with PUVA for 24 hours. The expression of caspase 8 and caspase 3
      protein enhanced and reached the peak after treating with PUVA for 8 hours. It is
      concluded that the PUVA can inhibit the growth of HL-60 cells and induce
      apoptosis of these cells. The possible mechanism is supposed to be up-regulating
      Fas, down-regulating FasL levels and then activating the levels of caspase 8 and
      caspase 3. The decreasing of mitochondrial membrane potential may be involved in
      this process probably.

PMID- 19099631
TI  - [Effect of mitogen-activated protein kinases on ATRA-induced differentiation of
      NB4 cells].
AB  - The aim of this study was to observe the effect of p38MAPK inhibitor SB203580 on
      ATRA-induced differentiation of NB4 cells. The proliferation activity of cells
      was assayed by MTT method, the cell cycle was detected by flow cytometry, the
      differentiation of NB4 cells into granulocytes was measured by test of NBT
      reduction, the activity of extracellular signal-regulated kinase (ERK) was
      detected by substrate phosphorylation. The results showed that the ATRA in 0.01
      01 micromol/L inhibited the proliferation of NB4 cells in time-and dose-dependent
      manner and induced the differentiation of NB4 cells into myeloid; the ATRA
      stimulated ERK activity in this process; ERK inhibitor PD98059 could partially
      block ATRA effect, specific inhibitor of p38MAPK, SB203580, combined with ATRA
      also could partially block the effects of ATRA on inhibition of NB4 growth and
      induction of differentiation. It is concluded that the ATRA stimulates ERK and
      p38MAPK pathway in the process inducing differentiation of NB4 cells, the ERK and
      P38MAPK may be necessary for the ATRA-induced differentiation in NB4 cells.

PMID- 19099632
TI  - [Effect of arsenic trioxide on vascular endothelial growth factor-C and its
      receptor (VEGFR-3) in nude mice with gastric cancer].
AB  - This study was aimed to investigate the effect of arsenic trioxide (As2O3) on
      expression of vascular endothelial growth factor-C (VEGF-C) and its receptor
      VEGFR-3 in gastric cancer in order to clarify the role of As2O3 in
      lymphangiogenesis and metastasis of tumor. The gastric cancer model was
      established in nude mice by using gastric cancer cell line SGC-7901. As2O3 was
      injected to the two treatment groups (2.5 mg/kg and 5 mg/kg) and the same volume
      of saline solution was injected to the control group. Expression of VEGF-C and
      VEGFR-3 were detected by immunohistochemistry and were analyzed with QWin550cW
      image Acquiring & Analysis System. The results showed that the expression of VEGF
      C and VEGFR-3 in cancer cells significantly reduced in the arsenic -treated
      groups. The expression of VEGF-C and VEGFR-3 in 5 mg/kg group was significantly
      less than that in 2.5 mg/kg group. The gray ratio analysis confirmed that there
      were significant difference between control group and two treated group, as well
      as between 2.5 mg/kg-treated group and 5 mg/kg-treated group. It is concluded
      that As2O3 can inhibit expression of VEGF-C and VEGFR-3 of human gastric cancer
      xenografts in nude mice, which suggests that As2O3 may inhibit the
      lymphangiogenesis by suppressing the expression of VEGF-C and VEGFR-3.

PMID- 19099633
TI  - [Expression of G-CSF and GM-CSF receptors on CD34 positive cells in aplastic
      anemia and myelodysplastic syndrome patients and its significance].
AB  - This study was aimed to detect the ratio of CD34+ cells in bone marrow
      mononuclear cells (BMMNCs) and the expression rate of G(M)-CSFR on CD34+ cells in
      bone marrow of the patients with aplastic anemia (AA) and myelodysplastic
      syndrome (MDS). The ratio of CD34+ cells in BMMNCs and the expression rate of
      G(M)-CSFR on cells of 27 AA patients, 45 MDS patients and 20 controls were
      detected by flow cytometry (FCM). The results showed that the ratio of CD34+
      cells in BMMNCs of AA patients reduced and was significantly different from
      controls (p<0.05), the ratio of CD34+ cells in MDS patients elevated and was
      significantly different from controls (p<0.05). Compared with controls and MDS-RA
      patients, the ratio of CD34+ cells in MDS-RAEB patients significantly elevated
      (p<0.05), but there was no significant difference between MDS-RA patients and
      controls (p>0.05). The ratio of CD34+ cells in MDS-RA patients was significantly
      higher than that in AA patients (p<0.05). There was no significant difference in
      expression rate of G-CSFR on CD34+ cells between AA patients and controls, MDS
      patients and controls, AA patients and MDS patients, MDS-RA patients and MDS-RAEB
      patients (p>0.05). The expression rate of GM-CSFR in MDS patients was
      significantly higher than that in AA patients and controls (p<0.05), but there
      was no significant difference between AA patients and controls, MDS-RA patients
      and MDS-RAEB patients (p>0.05). In AA patients, the ratio of CD34+ cells in
      BMMNCs was less than 0.1% accounts for 6/8 SAA patients, compared with 2/19 in
      CAA (p<0.05). There was no correlation between the expression rate of either G
      CSFR or GM-CSFR and neutrophil count at diagnosis (r=0.058 and r=0.044). In MDS
      patients, there was no correlation between bone marrow CD34+ cells ratio and
      peripheral neutrophil count at diagnosis (r=-0.335). And there was no correlation
      between the expression of either G-CSFR or GM-CSFR and neutrophil count on
      diagnosis (r=0.064 and r=0.051). It is concluded the detection of CD34+ cells and
      their surface expression rate of G(M)-CSFR in AA and MDS is useful in diagnosis
      and differential diagnosis of these two diseases.

PMID- 19099634
TI  - [Efficacy of different thalidomide regimens for patients with multiple myeloma
      and its relationship with TNF-alpha level].
AB  - The study was aimed to investigate the clinical efficacy and adverse reactions of
      different thalidomide regimens in the treatment of multiple myeloma (MM), and to
      explore the relationship between efficacy of thalidomide and serum level of TNF
      alpha in MM patients. The 85 patients with MM were divided into 5 groups
      according to different combinations of thalidomide. These 5 groups were
      following: group with the high dose (HD-T), group with thalidomide+VAD
      chemotherapy (T-VAD), group with thalidomide+MP chemotherapy (T-MP), group with
      thalidomide plus dexamethasone (TD), and group with low dose of thalidomide (LD
      T). Except 5 groups mentioned above, the group with conventional VAD chemotherapy
      was served as the control. Clinical effects, adverse reactions, treatment-related
      mortality were observed. At the same time, serum levels of TNF-alpha in 30 cases
      of MM treated with thalidomide (15 cases effective and 15 cases ineffective)
      before and after treatment were detected by double-antibody sandwich enzyme
      linked immunosorbent assay (ELISA) and were compared with the clinical efficacy.
      The results showed that the efficient rate of HD-T, T-VAD, T-MP, TD, LD-T groups
      were 25.0%, 80.0%, 71.4%, 33.3%, 27.3% respectively; the efficacy of T-VAD, T-MP
      groups were significantly higher (p<0.05) than that of other groups and
      conventional VAD chemotherapy group. The incidence of significant adverse
      reactions (peripheral neuropathy, fatigue, abdominal distension and constipation,
      rash, edema, leukocyte and platelet decrease) in 5 groups were 75.0%, 30.0%,
      28.6%, 14.3%, 9.1% respectively, no IV grade toxicity and deep vein thrombosis
      were found. The treatment-related mortality was 0%. At the same time, it was
      found that the serum levels of TNF-alpha in ineffective group treated with
      thalidomide were 44.7+/-5.7 pg/ml and 46.3+/-4.0 pg/ml before and after
      thalidomide treatment, and there was no significant difference (p>0.05). The
      serum levels of TNF-alpha (27.3+/-6.4) pg/ml in the effective group after
      treatment was significantly lower than that before treatment (49.2+/-7.3) pg/ml
      (p<0.05). It is concluded that compared with conventional chemotherapy,
      thalidomide is a effective drug for treating MM patients. Thalidomide in
      combination with chemotherapy (T-VAD, T-MP) may be one better therapeutic regimen
      with high efficiency and milder adverse reactions. Serum level of TNF-alpha is an
      indicator for finding effects of thalidomide, and plays a role in the
      pathogenesis of MM.

PMID- 19099635
TI  - [Fluorescence immunophenotyping and interphase cytogenetics as a tool for the
      investigation of cytogenetic aberrations of multiple myeloma].
AB  - This study was aimed to establish the technique of fluorescence immunophenotyping
      and interphase cytogenetics as a tool for the investigation of neoplasms
      (FICTION) used to smear of bone marrow, so as to develop a new technique for
      detection of the molecular cytogenetic abnormalities in multiple myeloma (MM). By
      using the bone marrow smear as the carrier and the anti-CD138 antibody linked
      with FITC, direct fluorescence staining was applied to mark plasma cells (PCs)
      and differences were compared in the proportion of both PCs marked by
      fluorescence staining and PCs detected in morphology. At the same time, the
      chromosome 8 centromere probe was used in interphase fluorescence in situ
      hybridization (I-FISH) for detection of the chromosome 8 abnormalities in PCs
      marked by fluorescence staining. The results showed that there was no significant
      difference between the proportions of both PCs marked by fluorescence staining
      and PCs detected in morphology on smear (p>0.05). 4 out of 9 patients (44%) had
      the chromosome 8 abnormalities, including 3 cases with -8 (33%) and one case with
      +8 (11%). It is concluded that the FICTION technique on the basis of bone marrow
      smear is characterized by convenience, specificity and accuracy. Therefore, it
      can be used for molecular cytogenetic research in MM.

PMID- 19099636
TI  - [Apoptosis and cell cycle arrest in lymphoma Raji cells induced by arsenic
      trioxide].
AB  - This study was aimed to investigate the apoptosis induced by arsenic trioxide
      (As2O3) in lymphoma Raji cells and its possible mechanisms. The inhibitory effect
      of different concentration of As2O3 on cell proliferation was tested by MTT
      assay. Apoptosis was observed with electron microscope and DNA electrophoresis.
      The distribution of cell cycles and cell apoptosis were detected by flow
      cytometry. The results showed that the 1-8 micromol/L As2O3 inhibited Raji cell
      growth effectively in a dose-and time-dependent manner. As2O3 at 2-8 micromol/L
      could induce the cell apoptosis and cell cycle arrest. However, As2O3 at 1
      micromol/L inhibited Raji cells proliferation only by cell cycle arrest, without
      any signs of cell apoptosis. In conclusion, substantial proliferation inhibition,
      cell cycle arrest and apoptosis in Raji cells could be induced by As2O3. Cell
      cycle arrest happens with apoptosis, when treated with As2O3.

PMID- 19099637
TI  - [Comparative analysis between autologous and allogeneic hematopoietic stem cell
      transplantation in 114 adult patients with acute lymphoblastic leukemia in long
      term follow-up].
AB  - This study was aimed to explore the effect of autologous hematopoietic stem cell
      transplantation (auto-HSCT) and allogeneic hematopoietic stem cell
      transplantation (allo-HSCT) in adult patients with acute lymphoblastic leukemia
      and to analyze the related prognostic factors. Clinical data of 114 ALL patients
      receiving HSCT, including 70 auto-HSCT and 44 allo-HSCT, were retrospectively
      analyzed. Disease-free-survival (DFS), relapse-rate (RR) and transplantation
      related-mortality (TRM) of patients receiving different HSCT were compared. The
      results showed that the eight-year OS and DFS in a total of 114 adult ALL
      patients were (40.89+/-5.27)% and (39.50+/-5.22)% respectively. The three-year
      DFS of ALL patients who received HSCT in phase CR1 and no CR1 were (47.63+/
      5.63)% and (17.65+/-9.25)% (p=0.0034). The two-year DFS of patients who received
      allo-HSCT and had I/II aGVHD was (62.75+/-12.30)%, and the six-month DFS of
      patients who had III/IV aGVHD was 0, and the two-year DFS of patients without
      aGVHD was (29.35+/-9.70)% (p=0.005). The three-year DFS of patients with and
      without maintenance chemotherapy after transplantation were (55.12+/-7.89)% and
      (33.33+/-11.11)% respectively, there was significant difference between them
      (p=0.0499). The five-year DFS between patients received auto-HSCT and allo-HSCT
      in phase CR1 was not significantly different. The RR of patients received allo
      HSCT was lower than that of patients received auto-HSCT, but there was no
      significant difference between them. The TRM of patients received allo-HSCT was
      higher than of patients received auto-HSCT (p=0.0313). Expression of myeloid
      antigen and higher LDH level in diagnosis were poor- prognostic factors. It is
      concluded that auto-HSCT and allo-HSCT completed in phase CR1 may improve
      prognosis of the patient with ALL as a method for consolidation chemotherapy, but
      no significant difference exists between the two HSCTs. Patients receiving allo
      HSCT and having I/II aGVHD may achieve higher DFS. The maintaining chemotherapy
      for patients after auto-HSCT may improve therapeutic effect.

PMID- 19099638
TI  - [Allogeneic peripheral blood stem cell transplantation for 75 cases of
      hematologic malignancies].
AB  - The aim of this study was to explore the clinical effect and complications of
      allogeneic peripheral blood stem cell transplantation (allo-PBSCT) in hematologic
      malignancies through retrospective analysis of 75 patients (42 male, 33 female;
      aged from 13 to 72 years old) received allo-PBSCT from HLA matched (n=61) or
      haploidentical donors (n=14). 75 patients included 35 patients with chronic
      myeloid leukemia (CML), 30 patients with acute myeloid leukemia, 5 patients with
      severe aplastic anemia, 3 patients with acute lymphocytic leukemia, one patients
      with multiple myeloma and one patients with paroxysmal nocturnal hemoglobinuria.
      Conditioning regimens were (1) Cy/TBI or Bu/Cy; (2) Cy/TBI+Ara-C; (3)
      fludarabine+TBI/or (CTX+ATG). Minimal residual disease has been monitored
      regularly by PCR and FISH. Patients received cyclosporine A and methotrexate or
      ATG and anti-CD25 monoclonal antibody and mycophenolate mofetil for graft-versus
      host disease (GVHD) prophylaxis. Relapsing patients after transplantation
      received DLI and/or chemotherapy. Patient with CML were treated with imatinib.
      The results showed that 74 patients had hematopoietic reconstitution, and
      eventually converted to full donor chimerism by FISH or PCR-STR. The median time
      for the initial hematopoietic reconstitution was 15 (5-25) days. 46 out of 75
      patients were alive and median duration was 23 (2-61) months. Among 29 dead
      patients, 9 died of disease relapse, 7 died of III-IV grade of acute GVHD and 7
      died of severe infection (2 patients developed interstitial pneumonia). 9 out of
      14 patients received haploidentical transplantation were alive, and the time of
      event-free survival was 30 (6-53) months, the mean survival time of 5 died
      patients was 7 (2-17) months. 16 patients were infected by cytomegalovirus, 2 of
      them died of interstitial pneumonia. None of them suffered from veno-occlusive
      disease in the liver. It is concluded that allo-PBSCT is effective to treat
      refractory hematologic diseases, and DLI/or chemotherapy should be used in the
      patients relapsing after transplantation.

PMID- 19099639
TI  - [Effect of intra-bone marrow infusion of allogeneic mesenchymal stem cells on
      reconstruction of marrow mesenchymal stem cells in rat HSCT models].
AB  - This study was aimed to investigate the effect of intra-bone marrow (IBM)
      injection of allogeneic mesenchymal stem cells (MSCs) on reconstruction of bone
      marrow MSCs (BM-MSCs) in rats that received hematopoietic stem cell
      transplantation (HSCT), and to detect the donor MSCs in the hosts for clarifying
      the effect mechanism of donor MSCs. Wistar female rats conditioned with lethal
      dose 60Co gamma-ray irradiation were co-transplanted with F344 female fetal and
      neonatal peripheral blood (FNPB) and BrdU-labeled MSCs separated from bone marrow
      mononuclear cells of F344 male rats. The donor MSCs were infused by IBM injection
      in bilateral tibia or intravenous injection (IV), while the FNPB were all via IBM
      route. The survival rate, engraftment level of HSCs and recovery of BM-MSCs of
      recipients were monitored. The ratio of BrdU-labeled MSCs in recipient rats was
      calculated by immunofluorescence assay (IFA) and the Y chromosomes were examined
      by PCR. The results showed that the recipient rats of the two co-transplantation
      groups were all alive at day 60 after transplantation. There was no significant
      difference between these two groups on the survival rates or the engraftment
      levels of HSCs, but each of them was much better than that of the FNPB group. At
      day 30 after transplantation, the proliferation ability of recipients' BM-MSCs
      was still below normal, while that of the FNPB (IBM)+MSC (IBM) group was the best
      of all the experiment groups (p<0.01). At 60 days, the donor MSCs coexisted with
      host MSCs in only a few recipient rats examined by IFA, while the Y chromosomes
      could be detected in all the recipient rats in the two cotransplantation groups.
      It is concluded that the infusion of allogeneic MSCs can accelerate the recovery
      of HSCT recipients' BM-MSCs. The IBM route is safe and more effective than
      intravenous infusion.

PMID- 19099640
TI  - [Establishment of sensitized animal models and their sensitization effects on
      engraftment of hematopoietic stem cells].
AB  - This study was aimed to establish sensitized animal models, explore the changes
      of immune function in these sensitized recipients, and investigate effects of
      sensitization on the engraftment of hematopoietic stem cells (HSCs). Different
      doses of spleen cells (1x10(5), 1x10(6) and 1x10(6)x2 at intervals of 7 days)
      from C57BL/6 were infused into BALB/c, the immunity function of sensitized models
      was tested by complement-dependent cytotoxicity method, mixed lymphocyte reaction
      and ELISA. After irradiation with gamma-ray of 60Co in dose 8 Gy, sensitized mice
      were transplanted 1x10(7) C57BL/6 bone marrow cells via tail vein or intra-bone
      marrow, and survival rate was detected daily. The results showed that different
      levels of donor reactive antibody were induced in all sensitized models.
      Comparing with normal mice, profound proliferation of spleen cells were found in
      groups of injected 1x10(6) and 1x10(6), continuous injections at intervals of 7
      days. Sensitized model received bone marrow cells of C57BL/6 via tail vein died
      on day 10 to 14 after transplantation, and sensitized model mice received bone
      marrow cells of 1x10(6)x2 at intervals of 7 days via intra-bone marrow also died
      within two weeks after transplantation. It is concluded that different sensitized
      mouse models are established by different doses of allogeneic spleen cells
      infusion, the changes of immune function in sensitized mice are correlative with
      sensitization. Donor HSCs are rejected in sensitized models, and the engraftment
      can not be improved by intra-bone marrow injection.

PMID- 19099641
TI  - [Correlation between CD34+CD61+ megakaryocyte precursors and platelet engraftment
      in allogeneic hematopoietic stem cell transplantation].
AB  - This study was purposed to investigate the correlation between the dose infused
      megakaryocytic precursors (CD34+, CD34+CD61+) and recovery time of platelet count
      following an allogeneic PBSCT and/or BMT through quantitative detection of CD34+
      and its subpopulation in peripheral blood and BM mobilized by G-CSF. 24 patients
      with various hematologic malignancies received PBSCT/BMT from their HLA matched
      or unrelated donors and haploidentical siblings in April-December 2007. 20
      evaluated patients were divided into 2 groups according to different transplant
      schemes. HLA matched group received PBSCT regime and haploidentical group
      received PBSCT combined with BMT. CD34+CD61+ subpopulations in sample from
      patients receiving PBSCT/BMT were measured by flow cytometry immediately or
      storage over night. The results showed that the median number of infused CD34+,
      CD34+CD61+ and CD34-CD61+ cells in haploidentical group were 6.24x10(6)/kg (1.53
      20.48), 66.19x10(4)/kg (8.16-493.83), and 34.38x10(6)/kg (14.71-109.16)
      respectively, in HLA matched group those were 4.88x10(6)/kg (1.00-8.24),
      14.16x10(4)/kg (11.63-96.87), and 13.50x10(6)/kg (1.74-35.61), respectively.
      Median days of ANCs>0.5x10(9)/L and platelets>20x10(9)/L were 18.5 (11.0-29.0)
      days and 16.5 (9.0-35.0) days in haploidentical group respectively; in HLA
      matched group those were 14.5 (9.0-24.0) and 10.5 (6.0-37.0) respectively. A
      significance difference of median days for ANC engraftment presented between two
      groups (p=0.048). There was no significant difference of time for platelet
      engraftment between 2 groups. For patients with CD34+ cell dose>2x10(6)/kg there
      was significant difference of time of platelet engraftment between HLA matched
      and haploidentical groups (p=0.006). The number of CD34+CD61+ cells infused in 12
      haploidentical patients or in 8 HLA matched patients were much better correlated
      with the time of platelet recovery up to 20x10(9)/L than that of number of CD34+
      cells infused in total 20 patients (r=-0.768 and p=0.004 for haploidentical
      CD34+CD61+ cells, r=-0.747 and p=0.033 for HLA matched CD34+ CD61+ cells, r=
      0.449 and p=0.047 for CD34+ cells). There was an inverse correlation between the
      number of infused CD34+ CD61+ cells and time of platelet engraftment. Therefore,
      as the number of CD34+ CD61+ cells increased, duration of platelet engraftment
      (time to reach platelet count of 20x10(9)/L) shortened significantly. It is
      concluded that the determining the number of megakaryocytic precursor by flow
      cytometry may predict the platelet reconstitutive capacity of the allogeneic
      hematopoietic stem cell transplantation, which is in haploidentical PBSCT and in
      BMT.

PMID- 19099642
TI  - [Detection of bcr/abl fusion gene changes in patients with chronic myeloid
      leukemia after allo-HSCT by real-time quantitative reverse transcription
      polymerase chain reaction and its significance].
AB  - This study was aimed to detect the changes of bcr/able gene level in ph+ CML
      patients at different stages after allo-HSCT by real-time quantitative PCR and to
      evaluate the significance of this detection. The serial detection of bcr/abl
      fusion gene levels in 21 cases of CML treated with allo-HSCT was performed by RQ
      PCR. The results showed that the bcr/able fusion gene could not be detected in 7
      out 21 CML cases with positive fusion gene after allo-HSCT, while the bcr/abl
      fusion gene of different levels could be detected in 14 cases within 1-6 months.
      Dynamic detection indicated that the bcr/abl fusion gene levels in 9 cases were
      lower with relative value 0.0074%-0.088% and then could not be detected within 3
      7 months after allo-HSCT. The bcr/abl fusion gene levels in 5 cases diagnosed as
      molecular relapse were between 0.077%-75%. The bcr/abl fusion gene levels in 1
      out of 5 cases were 0.95%, 1.5%, and 0.16% in month 1, 2 and 3, respectively, and
      turned to negative in the month 4 without any treatment after allo-HSCT. 2 cases
      received the donor peripheral blood stem cell infusion, and then their bcr/abl
      mRNA levels could not be detected in bone marrow. Another 2 cases developed to
      the hematologic relapse, 1 out of 2 cases reached CR again after infusion of
      donor peripheral blood stem cells and chemotherapy, the other one died. It is
      concluded that serial quantifications of bcr/abl mRNA levels by RQ-PCR are
      reliable and can be used to detect the MRD, to monitor the outcome and to predict
      the relapse.

PMID- 19099643
TI  - [Comparison of total body irradiation-cyclophosphamide versus busulphan
      cyclophosphamide as conditioning regimens for myelogenous leukemia: a meta
      analysis].
AB  - Total body irradiation combined with cyclophosphamide (TBI/CY) and busulphan
      combined with cyclophosphamide (BU/CY) are standard conditioning regimens in
      hematological stem cell transplantation for patients with myelogenous leukemia.
      This study was aimed to compare the therapeutic efficacy of TBI/CY and BU/CY as
      conditioning regiment for acute or chronic myelogenous leukemia. The Cochrane
      Central Register of Controlled Trials (CENTRAL), MEDLINE, CNKI, CBM (Chinese Bio
      medicine Database) had been searched for all relevant articles (1999-2007).
      Comparative studies were carried out on clinical therapeutic effects of TBI/CY
      and BU/CY including stem cell engraftment, relapse, complications, transplant
      related mortality, and disease-free survival. A meta-analysis was performed using
      Review Manager 4.2 software and funnel plot regression was adopted to assess the
      publication bias. The results indicated that 2149 articles in English and 46
      articles in Chinese were got, and finally 9 clinical trials with total 3039
      patients have been assessed. No significantly difference was found in engraftment
      failure and transplant-related mortality resulting from TBI/CY and BU/CY
      conditioning regimens, but the incidence of veno-occlusion of liver and
      hemorrhagic cystitis obviously increased in BU/CY group after transplantation,
      the acute GVHD, interstitial pneumonia and cataract significantly increased in
      TBI/CY group. The relapse rate of AML in TBI/CY group was lower than that in
      BU/CY group, and the rate of long-term disease-free survival of AML patients in
      TBI/CY group also significantly lower than that in BU/CY group, but the relapse
      rate of CML in TBI/CY group after transplantation was obviously higher than that
      in BU/CY group, but there was no difference in longterm disease-free survival
      rate between the two conditioning regimens mentioned above. It is concluded that
      the meta-analysis confirms different effects of TBI/CY and BU/CY regimens on
      myelogenous leukemia transplantation. This result is useful for physicians to
      select treatment regimens.

PMID- 19099644
TI  - [Establishment of method collecting peripheral blood hematopoietic
      stem/progenitor cells from infants].
AB  - The aim of this study was to explore a safe method collecting peripheral blood
      stem/progenitor cell (PBSPC) from the infants of body weight less than 20 kg by
      using the COBE Spectra Blood Cell Separator through Auto-PBSC procedure. After
      washing tube by normal saline, one unit of irradiated RBC was infused into the
      apheresis set. When the collection terminated, only the concentrated RBC in the
      apheresis set was returned to the infant. The peripheral mononuclear cells
      (PBMNCs) and CD34+ cells were counted, the cell viability was determined. The
      results showed that 13 PBSPC collections were carried out successfully from 7
      infants of body weight<20 kg. The average count of MNCs was 4.44x10(8)/kg [(3.46
      6.45)x10(8)/kg], the CD34+ count was 2.20x10(6)/kg [(1.34-3.79)x10(6)/kg] and the
      cell viability was 98.45% (97%-100%) respectively. The vital signs of all the
      infants went smoothly during collection of PBSPCs. In conclusion, with the aid of
      COBE Spectra blood cell separator and other measures, the collection of PBSPCs
      from infants of body weight<20 kg is safe and effective, the PBMNCs containing
      enough PBSPC can be harvested for transplantation.

PMID- 19099645
TI  - Effect of nerve growth factor on erythropoiesis in mice and its underlying
      mechanism.
AB  - This study was aimed to explore the effect of nerve growth factor (NGF) on
      erythropoiesis and to elucidate the underlying mechanism. Using flow cytometry,
      colony forming assay, blood cell counter, fluorescent real-time quantitation PCR,
      and enzyme-linked immunosorbent assay (ELISA), the changes in the bone marrow
      cells (BMCs) proliferation cycle, CFU-E and BFU-E counts, the peripheral blood
      erythroid related parameters, kidney EPO, BMC GM-CSF, spleen EPO receptor (EPOR)
      mRNA expression, and serum EPO, GM-CSF, and IL-1 concentrations were all
      determined after NGF was injected intramuscularly into the thigh of mice,
      meanwhile the change of BFU-E and CFU-E counts and its relationship with EPO, IL
      3 were investigated. The results indicated that the cell proportion in S+G2/M
      phase, the CFU-E and BFU-E counts of BMCs and the spleen EPOR mRNA expression in
      injection of NGF (7.5 microg/kg) for 7 days were significantly higher than that
      in injection of physiological saline for 13-19 days; red blood cell, hemoglobin,
      and reticulocyte counts increased as well. In vitro, NGF stimulated a dose
      dependent increase of CFU-E colonies formation in the semisolid culture system
      with or without exogenous EPO; the colony counts in the system with NGF alone
      were significantly higher than that in the system with exogenous EPO alone. The
      BFU-E counts in the system with exogenous NGF and IL-3 were significantly higher
      than that in the system with exogenous EPO and IL-3. It is concluded that the NGF
      promotes the responsibility of hematopoietic cells to EPO and activates the same
      signal transduction pathway as EPO in hematopoietic cells, and then accelerates
      the BMCs into mitosis, the HSCs differentiating into erythroid cells, and CFU-E
      and BFU-E formation.

PMID- 19099646
TI  - [Mesenchymal stem cells derived from human umbilical cord tissue modulate the
      secretion of antiplatelet antibody from splenocytes of ITP patients in vitro].
AB  - The study was aimed to investigate the potential immunotherapeutical values of
      umbilical cord tissue-derived mesenchymal stem cells (UC-MSC) on patients with
      chronic idiopathic thrombocytopenic purpura (ITP). UC-MSC was cocultured in vitro
      with splenocytes isolated from ITP patients who experienced splenectomy. The
      level of IgG antiplatelet antibody (PAIgG) was determined by a competitive micro
      enzyme-linked immunosorbent assay (ELISA) method. The proliferation of platelet
      reactive CD4+ T lymphocytes was also measured in the presence of UC-MSCs. The
      results showed that UC-MSCs could stimulate the spontaneous secretion of PAIgG in
      supernatants; In the platelet-inducing condition, UC-MSC inhibited the production
      of PAIgG at a low ratio of 1 UC-MSC to 100 splenocytes, but promoted at a high
      proportion of 1 UC-MSC to 10 splenocytes. Moreover, UC-MSC exerted a suppressive
      effect on proliferation of platelet-reactive T helper cells in a dose-dependent
      manner. It is concluded that the UC-MSCs can regulate secretion of antiplatelet
      antibodies in vitro. Its concrete regulation mechanism and potential
      immunotherapeutical value are need to further study.

PMID- 19099647
TI  - [Expression and activity of membrane surface tissue factor in peripheral blood
      cells of patients with cerebral infarction].
AB  - This study was aimed to investigate the expression and activity of membrane
      surface tissue factor (TF) of monocytes and platelets in peripheral blood cells
      from patients with cerebral infarction and their clinical significance. The TF
      expressions in monocytes and platelets from 25 patients with cerebral infarction
      were detected by flow cytometry, the TF activity was detected by chromogenic
      reaction method, and compared with 24 normal people used as control. The results
      showed that the TF expressions of monocytes and platelets in peripheral blood
      cells from patients with cerebral infarction were significantly higher than that
      in normal controls (p<0.01), and TF activity was also higher in patients than
      that in controls (p<0.01). In conclusion, the expression and activity of membrane
      surface in patients with cerebral infarction were enhanced, the hematocyte
      derived tissue factor as a trigger in coagulation pathway is involved in
      pathological thrombosis in patients with cerebral infarction.

PMID- 19099648
TI  - [Diagnostic significance of glycosylated ferritin for patients with secondary
      hemophagocytic lymphohistiocytosis].
AB  - This study was aimed to explore the level of glycosylated ferritin in the
      patients with secondary hemophagocytic lymphohistiocytosis (HLH) and its
      diagnostic significance. 29 suspected HLH patients from October 2007 to October
      2008 were enrolled in the study, and 25 healthy subjects were selected as
      control. The 29 suspected HLH patients were divided into confirmed group (22 out
      of 29) and unconfirmed group (7 out of 29) according to HLH-2004 diagnostic
      criteria. The percentage of glycosylated ferritin in peripheral blood was
      determined by phytohemagglutinin adsorption assay. The results showed that the
      median level of total serum ferritin in patients of confirmed group (2897.6+/
      1837.2 microg/L) was significantly higher than that in patients of unconfirmed
      group (653.1+/-249.1 microg/L) (p<0.01), and was also higher than that in
      controls (414.6+/-212.6 microg/L) (p<0.01). The median percentage of glycosylated
      ferritin in patients of confirmed group was significantly lower (17.0+/-4.2%)
      than that in patients of unconfirmed group (40.7+/-4.5%) (p<0.01) and was lower
      than that in controls (53.6+/-13.3%) (p<0.01). The sensitivity (86.4% vs 77.3%)
      and specificity (71.4% vs 42.9%) of glycosylated ferritin for the diagnosis of
      HLH were higher than that of total serum ferritin. In conclusions, glycosylated
      ferritin may be a helpful marker for the diagnosis of HLH.

PMID- 19099649
TI  - [Diagnostic significance of NK cell activity in the patients with hemophagocytic
      syndrome].
AB  - This study was aimed to explore the level of NK cell activity in the patients
      with secondary hemophagocytic syndrome (HPS) and its significance for early
      diagnosis of this disease. 16 suspected HPS patients and 25 healthy subjects were
      enrolled in this study. The activity of NK cells in peripheral blood was detected
      by a released LDH assay. The activity level of NK cells in peripheral blood from
      patients who were finally diagnosed as HPS was compared with healthy subjects.
      The results showed that 8 out of 16 suspected HPS patients were finally diagnosed
      as secondary HPS. The activity of NK cells in peripheral blood of these 8
      patients was obviously lower than that in healthy subjects with statistical
      significance (p<0.001), and showed abnormal in the early stage of this disease.
      It is concluded that the detection of NK cell activity may play an important role
      in earlier diagnosis of secondary hemophagocytic syndrome.

PMID- 19099650
TI  - [Effect of total body irradiation on cellular senescence related indexes of bone
      marrow mesenchymal stem cells].
AB  - The aim of this study was to explore the changes in cellular senescence related
      indexes of bone marrow mesenchymal stem cells (BMMSCs) after total body
      irradiation (TBI). At different time points after 4 Gy irradiation, BMMSCs were
      isolated from male C57BL/6 mice and cultured. Morphology, senescence-associated
      beta-galactosidase (SA-beta-gal) staining and cell cycle analysis were used to
      evaluate the changes in BMMSCs at cellular level while real-time RT-PCR was used
      to detect the alterations in senescence related gene expression including
      p16INK4a, p21Cip1/Waf1, p53 and TGF-beta1. The results showed that within 4 weeks
      after exposure to 4 Gy TBI, the morphology of BMMSCs and the expression level of
      SA-beta-gal were not significantly changed, the cellular senescence-related cell
      cycle arrest was not occurred and the senescence related gene expression level
      was not increased. It is concluded that at the early stage after 4 Gy TBI, the
      related molecular level of cellular senescence in BMMSCs is not changed.

PMID- 19099651
TI  - [Erythropoietin promotes proliferation of human bone marrow mesenchymal stem
      cells in vitro].
AB  - This study was aimed to investigate the effects of recombinant human
      erythropoietin (rhEPO) on proliferation of human bone marrow-derived mesenchymal
      stem cells (MSCs) in vitro. The aspirates of the bone marrow from healty
      volunteers were seeded in culture medium. Then MSCs were isolated according to
      characteristics adhering to the plastics. After three passages in culture, bone
      marrow-derived adherent cells were identified by growing morphological features,
      cell surface antigens and differentiation into multi-lineages. Then P3-MSCs which
      had been identified were incubated with different concentrations of rhEPO (0.5,
      1, 5, 10 and 50 U/ml). Subsequently, proliferation of MSCs was measured by MTT
      assay, as well as cell counts. At the same time, cell cycle was detected by flow
      cytometry (FCM). The results indicated that the expressions of CD90 and CD105 in
      P3 bone marrow-derived adherent cells were positive, while the expressions of
      CD34 and CD45 were negative, and these cells could differentiate into adipocytes,
      osteocytes and chondrocytes in induction media. MTT assay showed that the optical
      density (OD) of group treated with EPO was significantly higher than that in the
      control group (p<0.05), and the group treated with 50 U/ml EPO achieved the most
      predominant effects. The results of cell count were coincident with that of MTT
      assay. Furthermore, the cell cycle analysis by FCM revealed that rhEPO could
      relatively decrease the cell ratio in G0/G1 phase, and increase the cell ratio in
      S and G2/M phases. As compared with the control group, all those differences were
      statistically significant (p<0.01). It is concluded that erythropoietin can
      promote proliferation of human bone marrow mesenchymal stem cells in vitro, which
      may be correlated with the increased entry into S and M phases of cell cycle of
      MSCs adjusted by EPO.

PMID- 19099652
TI  - [Differences in megakaryocyte progenitor ex vivo expansion between CD34+ cells
      derived from human umbilical cord blood and bone marrow].
AB  - The purpose of this study was to explore the differences in megakaryocyte
      progenitor ex vivo expansion between CD34+ cells derived from human umbilical
      cord blood (CB) and bone marrow (BM). Mononuclear cells (MNCs) were obtained from
      CB or BM by Ficoll-Hypaque density gradient separation. CD34+ cells were purified
      by magnetic cell sorting (MACS). The selected CD34+ cells were seeded in serum
      free conditions stimulated with thrombopoietin (TPO), TPO+interleukin 11 (IL-11),
      or TPO+IL11+heparin for 14 days. Amplification product (CD34+, CD41a+, and CD34+
      CD41a+ cells) immunophenotypes, megakaryocyte apoptosis rates and the DNA content
      were measured by fluorescence-activated cell sorting (FACS). The colony-forming
      units of granulocytes and monocytes (CFU-GM), burst-forming units of erythrocytes
      (BFU-E), and colony-forming units of megakaryocytes (CFU-Mk) were also evaluated
      by the colony-forming units (CFU) assay. The results indicated that CD34+ cells
      derived from CB showed higher expansion ability of total cell counts, CD41a+ and
      CD34+ CD41a+ cells than those derived from BM for all days 14 of culture (p<0.05,
      respectively). There were no significant differences in CFU-GM, BFU-E, and total
      CFU-Mk counts between CB and BM-derived CD34+ cells on day 0 (p>0.05,
      respectively), but CB-derived CFU-Mk seemed mainly large colonies, and the number
      of large colonies was higher than that from BM (p<0.05) on day 0. There were no
      significant differences in expansion ability of CFU-GM between CB and BM-derived
      cells on days 7, 10, and 14 of culture (p > 0.05, respectively), but the
      expansion ability of BFU-E and CFU-Mk derived from CB cells was higher than that
      from BM (p<0.05, respectively). There were no significant differences in
      apoptosis rates of megakaryocyte from two source cells for days 14 of culture.
      Megakaryocytes derived from CB mostly showed the 2N DNA content (>90%) for days
      14 of culture, while those cells derived from BM showed the increased DNA
      content, and 4N, 8N or more ploidy cells gradually increased with prolonging of
      culture time. It is concluded that CB-derived CD34+ cells have a greater
      proliferation potential than that derived from BM, which is therefore proven to
      be a better cell source for megakaryocyte progenitor expansion in vitro.

PMID- 19099653
TI  - [Influence of mesenchymal stem cells on UCB CD34+ cell expansion and
      characteristics].
AB  - The aim of this study was to investigate the support effects of mesenchymal stem
      cells (MSCs) on umbilical cord blood (UCB) CD34+ cell (HSPC) expansion in vitro
      and its influence on cell characteristics including the surface marker of CD34+
      cells, homing adhesion molecules and colony-forming ability. The mononucleated
      cells (MNCs) were isolated from UCB, then the CD34+ cells were isolated from
      freshly obtained MNCs by immunomagnetic beads, the MSC feeder cells exposed to
      gamma-ray of 137Cs were prepared by MSC feeder. The CD34+ cells were inoculated
      in different culture media. Experiment was divided into 3 groups: HSPC+CK group
      in which cytokines were added to medium (SCF, FL and TPO); HSPC+MSC group in
      which CD34+ cells were inoculated on MSC feeder; HSPC+MSC+CK group in which
      cytokines and MSC feeder cells were added to medium. After culture for 4, 7, 10,
      14 days the MNC amount was counted and expansion ability of CD34+ cells was
      evaluated. The immunotypes of CD34+ cells and subsets, homing adhesion molecules
      and colony-forming ability in different groups detected by flow cytometry. The
      results showed that the amount of MNCs and CD34+ cells all obviously increased
      during culture for 14 days, the expansion levels of MNCs in 3 groups were
      HSPC+MSC+CK group>HSPC+CK group>HSPC+MSC group in proper order. Within 10 days of
      expansion in vitro amount of MNCs obtained significant expansion, meantime the
      expansion of CD34+ cells was higher also. The CD34+ count in 3 groups at day 4 of
      culture decreased significantly as compared with 0 day of culture (p<0.01). The
      CD34+ cells ratios in 3 groups after expansion were HSPC+MSC group>HSPC+MSC+CK
      group>HSPC+CK group in proper order (p<0.01), while CD34+ subset levels in 3
      groups were different, the CD34+CD38- cells in HSPC+CK group at 4 days of culture
      increased transiently (62.71%), then quickly decreased, the CD34+CD38- cell ratio
      at day 7 was 0.05%, while the CD34+CD38- cell ratio in HSPC+MSC group at day 7
      was 18.92%, difference was significant as compared with HSPC+CK group (p<0.05).
      The analysis of colony-forming units showed that the colony-forming ability at
      various time points after expansion all sustained in high level. It is concluded
      that in short-time (<7 day) culture of UCB CD34+ cells the combination of MSCs
      with cytokines can significantly expand the CD34+ cells and make the HSPCs to
      maintain original biologic characteristics.

PMID- 19099654
TI  - [Immunoregulation effects in vitro of the xenoprotein in combination with
      recombinant human granulocyte-macrophage colony stimulating factor and bacillus
      Calmette-Guerin].
AB  - This study was aimed to investigate the effects of xenogeneic antigen neu-Fc in
      combination with the recombinant human granulocyte-macrophage colony stimulating
      factor (GM-CSF) and Bacillus Calmette-Guerin (BCG) on the regulation of Th1 and
      Th2 immune response in vitro. The rat neu L2-S2 domain was engineered as a
      chimeric protein with human IgG Fc. The eukaryotic expression vector was
      constructed. The recombinant protein was stably expressed in CHO cells and
      purified by rProtein A Sepharose Fast Flow column. The recombinant protein was
      identified by SDS-PAGE and Western blot. Peripheral blood mononuclear cells
      (PBMNCs) were obtained by means of standard Ficoll separation from the blood of
      healthy donors. Neu-Fc-induced PBMNC proliferation was tested by MTT. The
      production of IL-12 and IL-10 was measured by ELISA. The results showed that the
      level of IL-12 decreased and IL-10 increased after PBMNCs were incubated with MCF
      7 cultural supernatant. 10 nmol/L neu-Fc strongly induced the cell proliferation.
      Compared with neu-Fc or GM-CSF or BCG treatment alone, neu-Fc in combination with
      GM-CSF and BCG significantly stimulated IL-12 production and inhibited IL-10
      production (p < 0.01). It is concluded that the neu-Fc can stimulate the
      proliferation activity of PBMNCs. neu-Fc, GM-CSF and BCG costimulation
      efficiently induces Th1 immune response.

PMID- 19099655
TI  - [Inhibition effect of rhEPO on rhIL6-induced hepcidin mRNA expression in HepG2
      cell lines and human primary hepatocytes].
AB  - This study was aimed to investigate the effect of rhIL-6 and rhEPO on hepcidin
      mRNA expression in HepG2 cells and human primary hepatocytes, and mechanism of
      rhEPO in treatment of anemia of chronic disease (ACD). The HepG2 cells and human
      primary hepatocytes were cultured with medium containing different concentrations
      of rhIL-6 and rhEPO for a certain time, then mRNA was isolated and its RT-PCR was
      performed, the bands were photographed and analyzed by UVI band, the hepcidin and
      G3PDH mRNA ratio were semi-quantitatively analyzed. The expression levels of
      hepcidin in GepG2 cells and human primary hepatocytes at different conditions
      were compared. The results showed that the hepcidin mRNA expression in HepG2
      cells and human primary hepatocytes could be enhanced by rhIL-6, the rhEPO could
      inhibit rhIL6-induced hepcidin mRAN expression. The rhEPO alone basically did not
      influence hepcidin mRNA expression in HepG2 cells. It is concluded that Hepcidin
      mRNA expression in HepG2 cells and human primary hepatocytes can be elevated by
      rhIL-6 with concentration- and time-dependent manner in certain range. rhEPO can
      inhibit this effect of rhIL-6.

PMID- 19099656
TI  - [Methylation of Id4 gene promoter in 4 malignant hematopoietic cell lines].
AB  - This study was purposed to investigate the status of Id4 gene promoter
      methylation in malignant hematologic cell lines. MS-PCR methods were used to
      detect the status of Id4 gene methylation in K562, HL-60, Ramous and CA46.
      Meanwhile bone marrow cells in healthy individuals and Hek937, a benign renal
      cell line, were involved as control. The results showed that Id4 gene kept
      unmethylated in bone marrow cells from healthy individuals and Hek937 cells,
      while Id4 gene was methylated in all of K562, HL-60, Ramous and CA46 cell lines.
      It is concluded that different from healthy bone marrow cells and non-malignant
      cell line Hek937, Id4 gene was methylated in leukemia and lymphoma cell lines
      including K562, HL-60, Ramous and CA46. The change of Id4 gene methylation is
      thought to be associated with occurrence of hematologic malignancies.

PMID- 19099657
TI  - [MPLW515L point mutation in patients with myeloproliferative disease].
AB  - In order to investigate the frequency of MPLW515L and JAK2V617F point mutations
      of the patients with myeloproliferative disease (MPD) in Nanjing area, MPLW515L
      and JAK2V617F point mutations were simultaneously detected by alleles specific
      polymerase chain reaction (AS-PCR) and sequencing in 190 MPD patients. The
      results showed that MPLW515L point mutation was detected in 1 out of 102
      essential thrombocythemia (ET) patients (1.0%) and was not detected in 32
      polycythemia vera (PV) patients, 13 idiopathic myelofibrosis (IMF) patients, 43
      chronic myelogenous leukemia (CML) patients. JAK2V617F point mutation was
      detected in 20 out of 32 PV patients (62.5%), 43 out of 102 ET patients (42.2%),
      5 out of 13 IMF patients (38.5%), and was not detected in 43 CML patients. It is
      concluded that MPLW515L point mutation exists in ET patient, but is not found in
      PV, IMF and CML. JAK2V617F point mutation exists in PV, ET and IMF, but not in
      CML.

PMID- 19099658
TI  - [Establishment of the tax gene expression cell lines and their biological
      activity].
AB  - This study was aimed to establish the cell lines of human T-cell leukemia virus
      type-1 (HTLV-1) tax gene expression and their biological activity. The eukaryotic
      vector pCMV-tax and pCMV-neo-Bam were transfected into Jurkat E6-1 by using
      liposome, following screening with G418, the tax gene expression cell line-TaxP
      and the negative cell lines-TaxN were selected and enriched. Then, the mRNA
      expressions of LAT, SLP70, ZAP70 and NF-kappaB (p65) were measured by using RT
      PCR; the NF-kappaB bioactivity was tested after transfecting the pNF-kappaB-Luc
      plasmids into TaxP and TaxN cells; meanwhile CD25, CD69 expressions on surface of
      the two cell lines were tested by flow cytometry. The results showed that TaxP
      and TaxN cell lines were established and the tax gene expression was detected; as
      compared with TaxN, the mRNA expressions of LAT, SLP70 and ZAP70 in TaxP were
      enhanced (p<0.05), while the NF-kappaB bioactivity in TaxP cells was stronger
      than that in TaxN cells (p<0.01). The CD25, CD69 on TaxP cells surface was highly
      expressed. It is concluded that TaxP and TaxN cell lines are established, TAX
      protein could promote the activation of T cells and activate the NF-kappaB
      pathway.

PMID- 19099659
TI  - [Effects of recombinant human thrombopoietin on stromal cells in culture in
      vitro].
AB  - This study was aimed to investigate whether the thrombopoietin (rhTPO) may
      facilitate myelofibrosis or not. The modified Dexter culture system with various
      concentrations of rhTPO was used to culture the stromal cells in vitro; the
      proliferative activity of cells was detected by MTT method; the morphologic
      changes were observed by light and scanning electron microscopy; the staining
      changes of ALP, PAS, AS-D NCE and IV type collagen were observed by cytochemistry
      method; the changes of fibronectin, laminin and IV type collagen were assayed by
      immunohistochemistry method; the cell surface antigens were assayed by flow
      cytometry. The results indicated that rhTPO could promote the proliferation of
      stromal cells which was related to the concentrations of rhTPO. Proliferative
      activity of stromal cells increased with increasing of rhTPO concentration, and
      was not related to the exposure time. On day 3 stromal cells adhered to the wall,
      and became oval. On day 7 stromal cells turned to fusiform and scattered
      dispersively. On day 12 to 14 these cells ranged cyclically and became long
      fusiform. Cells covered 70%-80% area of bottle bottom at that time. By day 16 to
      18 these cells covered more than 90% area of bottom and ranged cyclically. They
      displayed the same shape as fibroblasts. By light microscopy with Wrights-Giemsa
      staining, fibroblasts predominated morphologically, few macrophages, endothelial
      cells and adipose cells were found. There were no significant differences between
      experimental group and control group. On day 14 to 42 the adherent cells were
      positive with PAS staining, poorly positive with ALP and naphthol AS-D
      chloroacetate esterase (AS-D NCE) staining, and the difference in cytochemistry
      was not significant between two groups. When these cells were dyed with Masson's
      trichrome and Gomori's staining, neither collagen fibers nor reticular fibers
      were positive, but fibronectin, laminin, and collagen type IV appeared positive
      stronger in experimental group than those in control. The expressions of these
      molecules were not dependent on culture time. By scanning electron microscopy
      microvilli and fibers on cell surface appeared more and more, monolayer cells
      evolved into multilayer cells, and newly-formed fibroblasts appeared gradually as
      culture time prolonged. These alterations were not different among various
      groups. The expressions of CD34, CD45, CD105, CD106, and CD166 were not affected
      obviously by rhTPO. It is concluded that rhTPO had no effects on histochemical
      properties of stromal cells. Fiber staining and scanning electron microscopic
      examinations revealed that rhTPO can not facilitate fiber formation of stromal
      cells. But rhTPO may be able to augment the expressions of fibronectin, laminin
      and collagen type IV of stromal cells. Therefore it is still necessary to follow
      up the patients for a long time, who have received rhTPO therapy clinically.

PMID- 19099660
TI  - [Influence of different gelatin concentration and lymphocyte isolation liquid on
      primary culture of umbilical cord blood derived adhesive cells].
AB  - In order to study the influence of different gelatin concentrations, and
      lymphocyte isolation liquid on primary culture of umbilical cord blood-derived
      adhesive cells (hCBACs), the red blood cells of umbilical cord blood was
      separated by 3% and 6 % gelatin for detecting the effectiveness of sedimentation,
      then the adhesion rate at 48 hours, the day of initial expansion and the rate of
      culture success were detected for hCBACs cultured with CD34(+) cells after the
      mononuclear cells were separated by 6% gelatin followed by Ficoll and Percoll,
      and the morphological characteristics and growth status were observed by invert
      microscopy. Cytochemistry stain for nonspecific esterase stain (NSE), peroxidase
      (POX), periodic acid Schiff reaction (PAS) and alkali phosphatase (ALP) and
      immunocytochemistry labeling for CD31, CD45, CD68 and fibronectin (Fn) were
      detected. The results showed that 6 % gelatin was better than that 3% gelatin for
      red blood sedimentation. The Percoll was predominant over Ficoll in adhesion rate
      at 48 hours, the day of initial expansion, the time of initial formation of
      adhesive cell colony units, the time of maximal numbers of adhesive cell colony
      units, the the cell fusion time and ratio of culture success. 60% fibroblast
      liked cells, 36% macrophage liked cells and 4% small-round cells were observed in
      cells isolated by both isolated methods. The cytochemistry stain for NSE, POX,
      PAS and ALP was similar in two groups, the difference was not statistically
      significant between these two groups. The immunocytochemistry labeling for CD31,
      CD45, CD68 and Fn was also similar in both groups and the difference was also not
      statistically significant between these two groups. It is concluded that the
      combination of 6% gelatin with Percoll is an ideal separation method for primary
      culture of hCBACs, which provides basic information for clinical application.

PMID- 19099661
TI  - [Inhibitory effect of trehalose on phosphatidylserine exposure, osmotic fragility
      and membrane lipid peroxidation damage of erythrocytes induced by high
      concentration of glucose].
AB  - Though high concentration of glucose can benefit the survival of lyophilized
      human red blood cells, the high concentration of glucose can result in serious
      damage of red blood cells. This study was aimed to investigate the inhibitory
      effect of trehalose on damage of red blood cells induced by high concentration of
      glucose. After incubation with the high concentration of glucose buffer
      containing different concentrations of trehalose for three hours at 37 degrees C,
      the phosphatidylserine exposure and the osmotic fragility of cells were analyzed
      by flow cytometry and the lipid peroxidation of membrane was evaluated by TBA
      method. The results showed that the high concentration of glucose could lead to
      phosphatidylserine exposure, osmotic fragility increase, and lipid peroxidation
      damage which were dependent on the glucose concentrations and incubation
      temperature. However, trehalose could effectively prevent the phosphatidylserine
      exposure, osmotic fragility increase, and lipid peroxidation damage induced by
      high concentration glucose. With increase of the trehalose concentrations. As the
      trehalose concentration increases, the phosphatidylserine exposure, maloni
      aldehyde concentration and cell debris rate decreased gradually. In conclusion,
      the high concentration of glucose can lead to phosphatidylserine exposure,
      osmotic fragility increase, and lipid peroxidation damage of red blood cells.
      However, trehalose can inhibit the damaging effects of high concentration of
      glucose on red blood cells, which may be useful for the application of sugars to
      lyophilization of red blood cells.

PMID- 19099662
TI  - [Effect of free hemoglobin on hemorrhagic shock in pigs: TNF-alpha, IL-6
      expressions in serum and rates of MODS after the blood transfusion].
AB  - This study was aimed to investigate the expressions of tumor necrosis factor
      alpha (TNF-alpha), Interleukin-6 (IL-6) in serum and the incidence of multiple
      organ dysfunction syndrome (MODS) in pigs with hemorrhagic shock after the blood
      transfusion simultaneously combined with different doses of free hemoglobin (FHb)
      so as to provide guidance of banked blood with high concentration of FHb during
      war injury through understanding effect of FHb on the animals. The different
      doses of FHb were given intravenously during the recovery of pig from shock, the
      vital signs and functional changes of vital organs were monitored and the
      incidence of MODS was determined, as well as the serum specimens were collected
      and the TNF-alpha, IL-6 levels in serum were detected by ELISA. The results
      showed that there were statistical differences of serum levels of TNF-alpha and
      IL-6 in pigs after FHb 10 mg/kg infusion, as compared to shock control group.
      There was significantly difference of the serum levels of TNF-alpha, IL-6 after
      FHb 15 mg/kg infusion, compared to the control group. The incidence of MODS
      increased significantly. It is concluded that the blood infusion containing high
      dose (more than 10 mg/kg) of FHb influences significantly on the cytokines in
      pigs with hemorrhagic shock, and increases damage of cytokines to vital organs
      and the incidence of MODS. The tolerance dose of the pigs to free hemoglobin is
      about 10 mg/kg or so. The infusion of blood with less than 10 mg/kg is relatively
      safe for pig in hemorrhagic shock.

PMID- 19099663
TI  - [Expression of RhD antigen on RBC of different RhD serotype by flow cytometry].
AB  - This study was purposed to establish the method of quantifying RhD antigen on red
      blood cells (RBC) by flow cytometry (FCM) and to explore the expression of D
      antigen on RBC of different RhD serotype. RhD(+) RBCs and RhD(-) RBCs were mixed
      in 1:1 ratio. Cells were stained by the indirect method (IgG anti-D as the first
      antibody, FITC-anti-IgG F(ab')2 as the second antibody), and the ratio of RhD(+)
      on RBCs was quantified by FCM. The optimal dosage of IgG anti-D was defined.
      Expression of RhD antigen on RBC of RhD(+), weak D, RhDel and RhD(-) type were
      detected by FCM. The results showed that optimal dilution of IgG anti-D
      monoclonal antibody was 1:4, 1x10(6) cells/50 microl. The percentage of D(+) RBC
      of RhD(+), weak D, RhDel and RhD(-) type were 96.8+/-2.97%, 79.5+/-9.88%, 47.8+/
      11.43%, 3.7+/-2.96%, respectively. The mean fluorescence intensity (MFI) of RhD
      antigen expression of RhD(+), weak D, RhDel and RhD(-) type were 33.3+/-6.21 Dal,
      18.6+/-5.39 Dal, 7.10+/-1.17 Dal, 0.79+/-0.55 Dal, respectively. In conclusion,
      there are significant differences of RhD antigen expressions among RBC of
      different RhD serotypes. The level of antigen on RhD(+) RBC is the highest and
      then weak D the next, while the level of antigen on RhDel RBC is the lowest
      level.

PMID- 19099664
TI  - [Changes of pathogens and susceptibility to antibiotics in hematology ward from
      years 2001 to 2005].
AB  - The purpose of this study was to determine the changes of pathogens in
      hematological ward and susceptibility of patients received chemotherapy to
      antibiotics. The pathogens were taken from blood, urine and sputum of patients
      who accepted chemotherapy from years 2001 to 2005, then were isolated and
      identified. The susceptibility test was performed by disk diffusion method. The
      results showed that the total of 418 strains were detected. Gram-negative
      bacteria were the most common of nosocomial infection. Pseudomonas aeruginosa,
      Enterobacter cloacae, E. coli account for the most of Gram negative- bacteria
      infection and most resistant to broad-spectrum penicillin, Acinetobacter
      baumannii showed a trend of increase. The ratios of gram positive bacteria and
      fungi were increased slowly, mainly as Enterococcus and Candida. Enterococcus is
      the most common cause of Gram-positive bacterial infection. Vancomycin resistance
      did not occur. It is concluded that Gram-negative bacteria are main cause of
      nosocomial infection in patients with hematological malignancies. Gram positive
      bacteria and fungi had been more frequent. Strains resistant to antimicrobial
      agents increase.

PMID- 19099665
TI  - [Myeloma stem/progenitor cells as new targets for therapy of multiple myeloma-
      review].
AB  - Multiple myeloma (MM) is characterized by a population of functionally
      heterogeneous cells, in which identifying the target cells causing molecular
      lesion is a fundamental issue. The resultant tumor stem/progenitor cells comprise
      only a minor portion of the myeloma cells, which give rise through
      differentiation to more committed progenitors as well as differentiated blasts
      that constitute the bulk of the tumor. Although they are rare as compared with
      fully differentiated plasma cells, MM stem/progenitor cells are likely
      responsible for the maintenance and progression of disease through the production
      of new tumor cells. Thus, this is the cell population which must be eradicated
      for successful treatment. This article reviewed apparently conflicting evidence
      pertaining to the cellular origins of MM and proposed that myeloma may originate
      in more cellular components. In this article, the nature of the target cells, the
      identification and phenotypic analyses of clonogenic myeloma cells, the signaling
      pathways within myeloma stem/progenitor cells and the target therapy related were
      reviewed as well.

PMID- 19099666
TI  - [New advance of research on prognostic factors in myelodysplastic syndrome-
      review].
AB  - Myelodysplastic syndrome (MDS) represents a heterogeneous group of myeloid
      malignancies characterized by abnormal differentiation and maturation of myeloid
      cells, bone marrow failure, and a genetic instability with enhanced risk to
      transform to acute myeloid leukemia. Many factors influence on the prognosis of
      MDS. The prognosis of MDS subtypes has been changing with the application of
      World Health Organization (WHO) classification and different new prognostic
      scoring system, the technology development of cytogenetics and flow cytometry,
      and the advent of new drugs. A series of recent literatures are summarized on
      different prognostic factors of MDS. In this review, the controversy in
      application of WHO classification, MDS prognosis in relation with prognostic
      scoring system, cytogenetics, immunophenotype and therapeutics were discussed.

PMID- 19099667
TI  - [Research progress on biological characteristics and clinical application of
      endothelial progenitor cells--review].
AB  - Endothelial progenitor cells are precursors of endothelial cells, which are able
      to differentiate into mature endothelial cells. Studies are needed to increase
      more detailed understanding on the mechanisms of EPC-differentiation, survival,
      homing and distribution of the tissue. The human EPC has potential to be used as
      diagnostic and prognostic or therapeutic tools in the future. This review
      describes recent studies on the biological characteristics and clinical
      application of EPC, including immunophenotype and functional characteristics of
      EPCs, mobilization, release and differentiation of EPCs, EPC number and
      recruitment, clinical application of EPCs, and so on.

PMID- 19099668
TI  - [Role of flow cytometric immunophenotyping in diagnosis of myelodysplastic
      syndromes--review].
AB  - Bone marrow morphology and karyotyping are effective ways to diagnose
      myelodysplastic syndromes. However, there are still many patients without these
      two abnormalities. Recently, there are considerable amount of evidence showing
      that flow cytometric immunophenotyping is a good approach to detect the abnormal
      differentiation and maturation of different cell lines and maturation stages of
      bone marrow cells in MDS patients. The highly reproducible results allow to
      distinguish MDS from other non-clonal hematocytopenia disorders and have a
      diagnostic advantage especially in case of low-risk MDS. Meanwhile, it showed a
      good correlation with the morphology and karyotyping, and with the International
      Prognostic Scoring System (IPSS) playing a prognostic role. This article reviewed
      recent advances of research in this field such as the application of FCM in MDS
      detection, the correlation of FCM parameters with morphologic and cytogenetic
      diagnosis of MDS as well as the relationship of parameters with typing and
      prognosis of MDS and so on.

PMID- 19099669
TI  - [New insight into DNA methylation in CML and its effect on clinical outcome-
      review].
AB  - All kinds of tumors have their specific DNA methylation patterns. The study of
      DNA methylation changes in chronic myelogenous leukemia includes (1) the
      hypomethylation of carcinogenic gene, (2) the hypermethylation of tumor
      suppressing gene, and (3) the hypermethylation of fusion gene. In this paper, DNA
      methylation change in chronic myeloid leukemia (CML) and its role in clinical
      stages and evaluation of prognosis were reviewed so as to illuminate the
      relationship between DNA methylation and CML.

PMID- 19099670
TI  - [Progress of study on survivin in diffuse large B-cell lymphoma--review].
AB  - Diffuse large B-cell lymphoma (DLBCL) is the most common type of non-Hodgkin's
      lymphoma (NHL), which is also a significantly heterogeneous disease. Survivin, a
      unique member of the inhibitor of apoptosis (IAP) family, is overexpressed in
      various cancers, including some types of lymphoma. It is found that inhibitor of
      apoptosis protein, survivin, plays an important role in the development and
      progression of DLBCL. Survivin is able to inhibit the cell apoptosis, and
      enhances the cell proliferation. Many studies showed that survivin may be
      considered as an independent unfavorable prognostic index of DLBCL. The poor
      prognostic cases early are screened in combination of survivin expression with
      International Prognostic Index (IPI), and improve the outcome of DLBCL. Survivin
      selectively expressed in tumor tissue, which provide an ideal target for tumor
      therapy. Modulation of survivin expression or function may provide a novel
      approach for experimental therapy in patients with DLBCL. In this review, the
      progress of study on mechanism of survivin protein, the survivin expression in
      DLBCL, its significance in diagnosis and therapy of DLBCL, and the prospective
      trend were summarized.

PMID- 19099671
TI  - Erythropoietin improves brain mitochondrial function in rats after traumatic
      brain injury.
AB  - Mitochondria play a central role in cellular energetics, calcium homeostasis and
      apoptosis. Our previous study demonstrates traumatic brain injury induces brain
      mitochondrial dysfunction after injury. Preservation and/or restoration of
      mitochondrial function may be one of the strategies for neuroprotection.
      Erythropoietin, a hormone for erythropoiesis, also provides tissue protection
      against traumatic brain injury and stroke. The present study was undertaken to
      evaluate the effect of erythropoietin on traumatic brain injury-induced brain
      mitochondrial dysfunction. Traumatic brain injury decreased rates of respiration
      at the active state (state 3), increased that at the resting state (state 4) and
      consequently decreased respiratory control index (state 3/state 4 ratio) and the
      efficiency of ATP synthesis (the amount of ADP phosphorylated by inorganic
      phosphate divided by the amount of oxygen consumed during state 3 respiration).
      Erythropoietin administered intraperitoneally 30 minutes post-injury at 1000 U/kg
      partially improved mitochondrial function at day 1 post-injury. However,
      erythropoietin-induced improvement was not sustained at day 7 post-injury.
      Erythropoietin at 2000 or 5000 U/kg restored states 3 and 4 examined at day 1
      post-injury to the sham levels. Consequently, the energy coupling capacities,
      such as respiratory control index and/or the efficiency of ATP synthesis, were
      also improved. The beneficial effect of erythropoietin at these doses persisted
      for at least 7 days post-injury. The beneficial effect of erythropoietin on brain
      mitochondrial function was observed with a wide therapeutic window from 5 minutes
      to 6 hours post-injury. Our data, for the first time, demonstrate that
      erythropoietin treatment restores brain mitochondrial function after traumatic
      brain injury, which will enhance cellular energy generation and reduce oxidative
      stress, strongly supporting erythropoietin as a promising agent for the
      therapeutic treatment of traumatic brain injury.

PMID- 19099672
TI  - The diagnostic value of erythrocyte sedimentation rate in management of brain
      tumors.
AB  - OBJECTIVE: Erythrocyte sedimentation rate (ESR) is considered as an indicator of
      inflammatory processes, and it has a prognostic value in the management of
      specific neoplastic diseases. It also responds to surgical intervention. There is
      very little data about the alteration of ESR in patients with brain tumors and
      information on its course after intracranial tumor surgery is completely lacking.
      METHODS: ESR was measured for 10 days in 46 patients (19 women and 27 men; mean
      age: 49.7 years; range: 13-70 years) who underwent elective craniotomy for tumor
      microsurgery (70-425 minutes with a mean of 230 minutes) under general
      anaesthesia. Blood samples were taken on the day before surgery and on each
      consecutive day after surgery for 10 days. The standard method of measuring ESR
      was based on the technique first described by Westergren. RESULTS: The mean ESR
      level on the day before surgery was 8.26 +/- 7.27 mm/h after 1 hour and 14.80 +/-
      10.36 mm/h after 2 hours. After tumor surgery, ESR increased stepwise. The mean
      peak value of 22.89 +/- 13.41 mm/h after the first hour was reached on the third
      post-operative day. Whereas mean values varied over time, ESR remained increased
      and did not decline to normal values until the tenth post-operative day. The mean
      ESR peak value was higher in patients having undergone surgery for intra-axial
      lesions (31.36 +/- 30.43 mm/h on the post-operative day 6) as compared to
      patients with extra-axial lesions (21.31 +/- 12.20 mm/h on the post-operative day
      3). CONCLUSION: ESR is not relevantly increased in patients harboring brain
      tumors. Because it remains elevated until the tenth post-operative day after
      uneventful craniotomy and generally responds more slowly than other indicators
      like C-reactive protein, it is also not suitable for the detection of post
      operative infective complications.

PMID- 19099673
TI  - Impact of statins on validation of ICH mortality prediction models.
AB  - BACKGROUND: Intracerebral hemorrhage (ICH) has the highest mortality rate of all
      strokes. Hemphill's ICH score is commonly used to predict mortality after ICH.
      More recently, the ICH grading scale (ICH-GS) has been shown to improve
      sensitivity of 30 day mortality prediction in this patient group. OBJECTIVE: To
      assess the impact of admission variables not included in prediction models, such
      as coagulopathy, hyperglycemia, seizures and previous aspirin or statin use on 30
      day mortality prediction using two contemporary prediction models. METHODS:
      Records of consecutive ICH patients from 1999 to 2006 were reviewed. Patients
      with ICH secondary to trauma or underlying lesions (e.g. brain tumors, aneurysms,
      arteriovenous malformations) and of infratentorial location were excluded. We
      dichotomized patients into a 'predicted survival group' and 'predicted death
      group' based on a <50% or >50% probability of death, respectively. The predicted
      mortality using ICH score and ICH-GS prediction models was calculated and was
      compared with the observed mortality in all patients and then separately in
      patient subgroups differentiated based on the presence or absence of
      coagulopathy, hyperglycemia (blood glucose> 180), seizures on presentation and
      previous exposure to aspirin or statins. Chi-square test was used for comparison
      of predicted and observed outcomes. RESULTS: One hundred and twenty-five patients
      were included in the analysis. The overall observed mortality was 23.2% (29/125),
      which was significantly lower than the 34.4% mortality predicted by ICH-GS
      (p=0.03). Hemphill's ICH score overestimated overall mortality by 7.2% (30.4
      23.2%); however, this difference was not statistically significant (p=0.14). In
      patients using statins before ICH, observed mortality was 38% (5/13) and 42%
      (5/12) of the predicted mortality using ICH-GS (p=0.03) and ICH score (p=0.04),
      respectively; this difference was not seen in patients not previously exposed to
      statins. ICH-GS (but not ICH score) significantly overestimated mortality in
      patients with a serum glucose <180 (p=0.02); none of the other factors analysed
      significantly impacted the two mortality prediction models. CONCLUSION: The
      significant difference between predicted and observed mortality using ICH-GS and
      the ICH score in the statin cohort suggests a protective effect of statins in the
      setting of ICH. Such observation warrants prospective validation.

PMID- 19099674
TI  - [Chronic cough in pediatrics--a common clinical symptom].

PMID- 19099675
TI  - [How should we understand the recurrent respiratory tract infections?].

PMID- 19099676
TI  - [Therapeutic efficacy and follow-up study of inhaled corticosteroids vs. oral
      montelukast in treatment of cough variant asthma].
AB  - OBJECTIVE: To compare the effects of inhaled corticosteroids (ICS) and oral
      leukotriene modifier (LTM) montelukast on the prognosis of children with cough
      variant asthma (CVA), and to identify the related risk factors for the
      development of classic asthma in children with CVA. METHODS: Eighty-four children
      with CVA (2 - 6 yrs) were randomized to receive inhaled beclomethasone
      dipropionate 200 microg/d through pressurized metered-dose inhaler (MDI) plus
      spacer with mask or oral montelukast 5 mg, once at bedtime for 6 months, then
      followed by 18 months observation period after the end of the study medication.
      RESULTS: There was no significant difference in antitussive days between the two
      groups (ICS group: 14 +/- 9 days, LTM group: 13 +/- 9 days, Z = 1.12, P = 0.25).
      Wheezing developed in 7.1% of the children in ICS group during 24 months follow
      up period, which was significantly lower than that in LTM group (33.3%, chi2 =
      8.92, P = 0.003). The prevalence of eczema or allergic rhinitis was higher in
      children who developed wheezing than those who did not develop wheezing (eczema:
      47.1% vs. 19.4%, chi(2) = 4.16, P = 0.042; allergic rhinitis: 58.8% vs. 31.3%,
      chi2 = 4.40, P = 0.036). Logistic regression analysis confirmed that eczema and
      allergic rhinitis were risk factors for wheezing development in children with
      CVA, the odds ratio was 7.668 and 3.855 respectively (P < 0.05 for all). But
      administration of ICS was negatively correlated with the development of wheezing
      by an odds ratio of 0.128 (P = 0.008). CONCLUSIONS: Children with CVA may
      progress to classic asthma; eczema and allergic rhinitis are two risk factors for
      wheezing development in children with CVA. Both ICS and LTM are effective
      antitussive treatment, but ICS may be more effective than LTM on preventing the
      progression of CVA to classic asthma.

PMID- 19099678
TI  - [Ohtahara syndrome with hemimegalencephaly: report of a case].

PMID- 19099677
TI  - [Association of RANTES gene promoter -28C/G polymorphism with respiratory
      syncytial virus bronchiolitis].
AB  - OBJECTIVE: Respiratory syncytial virus (RSV) infects nearly all children under
      two years of age. It is poorly understood why a few children who were infected
      with RSV develop bronchiolitis that require hospital admission while most have a
      relatively minor illness. Several recent studies have obtained some indications
      for the involvement of genetic heterogeneity in RSV bronchiolitis, implying that
      the clinical outcome of RSV infection perhaps is determined by genetic factors.
      Regulated on activation, normal T cell expressed and secreted RANTES plays a key
      role in the pathophysiology of RSV bronchiolitis. The purpose of this study was
      to explore the genetic association between the RANTES gene promoter -28C/G
      polymorphism and RSV bronchiolitis in Chinese Han ethnic group population.
      METHODS: The study recruited 238 hospitalized patients (186 male and 52 female)
      under 12 months of age, with a clinical diagnosis of bronchiolitis due to RSV,
      the sex, age, hospital stay, SaO2 at the time of admission, personal and family
      history of atopy were recorded. The 288 healthy control subjects (206 male and 82
      female), who had no evidence of personal or familial history of atopy and no
      history of wheezing, were chosen at the same time. Polymerase chain reaction
      restriction fragment length polymorphism (PCR-RFLP) was used to identify the
      polymorphism at position -28C/G of the RANTES promoter. The total IgE
      concentrations in serum samples were measured by enzyme-linked immunosorbent
      assay (ELISA). The absolute peripheral blood eosinophil counts were measured by
      using an automated hematology analyzer. RESULTS: The distribution of RANTES 
      28C/G gene polymorphism was in accordance with Hardy-Weinberg equilibrium.
      Compared to control subjects, significant difference was demonstrated for
      genotypes and allele frequencies of the RANTES -28C/G polymorphism in patients
      with RSV bronchiolitis (G = 10.22, P < 0.01; chi2 = 9.708, P < 0.01). Compared
      with the wild type CC, the -28G allele carriers demonstrated a 2.09-fold
      increased risk of RSV bronchiolitis (OR = 2.09, 95% CI = 1.32 - 3.30, P < 0.01).
      Interestingly, both the percentage of personal history of atopy and the
      percentage of family history of atopy for the -28G allele carriers were
      significantly higher (P < 0.05) than that for those CC homozygotes carriers in
      RSV bronchiolitis. Compared with the wild type CC, the -28G allele carriers
      demonstrated a 1.85-fold increased risk of the personal history of atopy (OR =
      1.85, 95% CI = 1.01 - 3.38, P = 0.045) and a 1.91-fold increased risk of the
      family history of atopy (OR = 1.91, 95% CI = 1.03 - 3.54, P = 0.037), and the
      absolute peripheral blood eosinophil counts for the -28G allele carriers were
      significantly higher (P < 0.05). CONCLUSION: The RANTES gene promoter -28C/G
      polymorphism is associated with the susceptibility to RSV bronchiolitis, and the 
      28G allele is an important predisposing factor for the personal history of atopy
      and the family history of atopy in RSV bronchiolitis.

PMID- 19099679
TI  - [Surveillance for influenza B virus infections in infants and young children in
      Beijing, China].
AB  - OBJECTIVE: To characterize the prevalence of influenza B virus infection in
      infants and young children in Beijing. METHODS: MDCK cell culture, indirect
      fluorescence assay (IFA) and hemagglutination inhibition (HI) assay were used to
      isolate and identify type B influenza viruses from clinical samples collected
      from outpatients and inpatients who visited the Affiliated Children's Hospital
      because of acute respiratory infections from Nov. 2000 to Jun. 2006. RESULTS: Out
      of 10,770 clinical samples collected during this surveillance period, 384 (3.57%,
      384/10,770) were positive for influenza B viruses. Circulation of influenza B
      viruses was revealed in the later epidemic season of influenza viruses each year.
      The detection rate for influenza B virus was higher than 10% each year during the
      survey, except in the period from 2003--2004 which was 2.91%. The highest
      detecting rate was 23.69% of the specimens collected in Mar. 2006. During the
      period of this study, most of the influenza B virus were identified from children
      who visited the outpatient department of the Affiliated Children's Hospital.
      Among those outpatients who were positive for influenza B, 77.6% (264/340) were
      older than 3 years of age, whereas the inpatients positive for influenza B, 66.0%
      (29/44) were under 3 years of age. Coinfection of influenza B virus with other
      respiratory viruses was not common, only one of the influenza B virus positive
      specimen was found also positive for influenza A3. There was no significant
      difference in positive rate between influenza virus B and A3. A significantly
      higher positive rate of influenza B virus than that of influenza A3 virus was
      seen from Sep. 2005 to May 2006 (23.9% vs 1.1%). B/Yamagata/16/168 lineage
      viruses were dominant during 2000--2002, and B/Victoria/2/87 lineage viruses
      became dominant during 2002--2003. After 2003, co-circulation of Victoria and
      Yamagata lineages of influenza B viruses was identified with predominance of
      Yamagata lineage viruses, while Victoria lineage viruses predominated during the
      2005--2006 epidemic season. CONCLUSION: Influenza B viruses were identified from
      February to May in every influenza season during this surveillance period of 2000
      -2006. Most of the positive specimens were those collected from outpatient
      department. Victoria and Yamagata lineages of influenza B viruses co-circulated
      in Beijing, China in recent years.

PMID- 19099680
TI  - [Peak inspiratory flow generated through different analogue dry powder inhalers
      in Shenzhen healthy preschool children].
AB  - OBJECTIVE: Dry powder inhalers (DPIs) are increasingly being used to deliver
      drugs for the treatment of asthma. It is known that DPIs require a crucial
      minimal inspiratory flow. Previous studies have demonstrated that the peak
      inspiratory flow (PIF, L/min) through a DPI is dependent on the type of device,
      the age of the patient, and the level of bronchial obstruction. However, the peak
      inspiratory flow of healthy preschool children in China remains scant in the
      literature. The present study aimed to analyze the ability of inspiring flow
      through the resistance state of ordinary use inhaler in Shenzhen healthy
      preschool children by measuring the peak inspiratory flow through the different
      analogue dry powder inhalers and go further into the relationship between it and
      the age, weight and forced expiratory volume of the children. METHOD: A survey in
      370 healthy preschool children aged 3 to 6 years (75 children aged 3 years, 104
      children aged 4 years, 100 children aged 5 years and 91 children aged 6 years)
      was carried out in Shenzhen. Peak inspiratory flow (PIF) was measured without and
      with resistances, which mimicked the internal resistances of several inhalers,
      Diskus, Turbuhaler, Autohaler, Surehaler by PIF meter (In-check DIAL) and then
      data PIF-N, PIF-D, PIF-T, PIF-A and PIF-S were obtained. Peak expiratory flow
      (PEF) was measured by PEF meter (MicroPeak, USA). These two measurements were
      made in a well-controlled setting, and at least three attempts were recorded to
      establish maximum achievement. Six spirometry parameters forced vital capacity
      (FVC), forced expiratory volume at 0.5 second (FEV 0.5), forced expiratory volume
      at 0.75 second (FEV 0.75), forced expiratory volume at one second (FEV1), maximal
      mid expiratory flow rate (FEF 25 - 75, PEF were measured by using COSMED
      spirometry of Italy and the FVC measurements should be around the quality control
      for spirometry in preschool children which we suggested and published in 2005.
      All data were expressed as mean +/- SD and analyzed with the statistical software
      SPSS 12.0 for Windows. Pearson's test was used for calculation of the
      significances of the correlation coefficients. Variance analysis was used for
      analysing the variability of inspiratory flows through the inhalers. RESULTS:
      Results were obtained from 295 children aged 3 - 6 years who successfully
      finished the tests. The PIF-N, PIF-D, PIF-T, PIF-A and PIF-S were significantly
      different among the groups aged 3 yrs, 4 yrs, 5 yrs and 6 yrs. The peak
      inspiratory flow significantly increased with age. The PIF-N, PIF-D, PIF-T, PIF-A
      and PIF-S in the children of 110 cm height and above were significantly higher
      than those in the children below 110 cm height, so were the parameters between
      the children of 120 cm height and above and the children below 120 cm. PIF
      correlated significantly with age, height and weight and the Pearson coefficient
      was 0.3 - 0.5. The PIFs in different inhalers varied because of the different
      inner resistances. The minimum and optimum PIFs in resistances of Diskus,
      Autohaler and Surehaler could be achieved in almost all subjects, but those in
      resistances of Turbuhaler could be achieved in only 87.5% subjects, most of whom
      aged 3 yrs or below 100 cm height. There were good correlations between the PIFs
      in different resistances and main parameters of ventilation function (FVC, FEV
      0.5, FEV 0.75, FEV1, FEF 25 - 75, PEF), PEF was the best among them (Pearson
      correlative coefficient was 0.6). CONCLUSION: The inspiratory ability of the
      children can be predicted and assessed by using routine measurement of lung
      function of normal pre-school children. As to the pre-school children of varying
      ages, the variety of inspiratory ability should be considered completely in the
      selection of inhaler used during the treatment. The best inhaler suitable for
      them should be selected properly in order to obtain the best efficacy of
      treatment individually.

PMID- 19099681
TI  - [Guideline for diagnosis and treatment of chronic cough in pediatrics].

PMID- 19099682
TI  - [A brief introduction to the 10th Annual Asian Symposium on lysosomal storage
      disease].

PMID- 19099683
TI  - [Clinical concept and management of recurrent respiratory tract infections in
      children (revised)].

PMID- 19099684
TI  - [Seroprevalence of antibody against human bocavirus in Beijing, China].
AB  - OBJECTIVE: To find out the importance of human bocavirus (HBoV) as an infectious
      agent for population in Beijing, China, seroprevalence study was conducted by
      using expressed recombinant major capsid VP2 protein as an antigen. METHODS:
      Serum specimens collected from infants and children who visited the Children's
      Hospital Affiliated to the Capital Institute of Pediatrics for health check up
      and adults visited the Xuanwu Hospital, Beijing for diseases other than
      respiratory infections from April 1996 to March 1997 were used for investigation.
      The major capsid protein VP2 from HBoV was expressed in E. coli strain BL21 (DE3)
      with the transformed PET30b vector inserted with full-length VP2 gene of HBoV and
      the specific antigenicity of this expressed protein was validated by previous
      study. Western blot was used to detect specific IgG antibody against HBoV in
      collected serum specimens diluted to 1:200. Mock expressed protein was E. coli
      cells strain BL21 (DE3) with the transformed PET30b vector without insert. Anti
      His monoclonal antibody and rabbit anti-HBoV VP2 polypeptides hyper-immune serum
      were used as positive control for antibody detection. RESULTS: Out of 677 serum
      specimens tested, 400 (59.1%) were positive by Western blot. About 45.3% (34/75)
      of the newborns under 1 month of age had anti-HBoV antibodies, and antibody
      positive rates were lower in the age groups of 1 and 2 months (41.4% and 31.3%,
      respectively) and were higher in the following ages from 6 months to 7 years
      (from 45.6% to 69.7%). The antibody positive rates were at a relatively constant
      level (about 70%) in the age groups from 7 years to 40 years and became lower
      (61.8% - 62.8%) in groups of age over 50 years. CONCLUSION: The high
      seroprevalence against recombinant HBoV VP2 protein and early age antibody
      acquisition indicate that HBoV has been circulating in Beijing, China as early as
      in 1996 and most of children had been exposed to HBoV by the age of 7 years.
      Infants under the age of 6 months were susceptible to infection with this virus.

PMID- 19099685
TI  - [Spectrum of phenylalanine hydroxylase gene mutations and genotype-phenotype
      correlation in the patients with phenylketonuria in Beijing area of China].
AB  - OBJECTIVE: To identify the mutation spectrum and the distribution of
      minihaplotypes (STR/VNTR) of phenylalanine hydroxylase (PAH) gene and explore the
      correlations between genotype and phenotype of patients with phenylketonuria
      (PKU) in Beijing area of China. METHOD: (1) Fifty cases with PKU were involved in
      this study. PKU was identified by the Neonatal Screening Center of Beijing. All
      13 exons and their flanking intronic sequences of PAH gene of these patients were
      amplified and then subjected to SSCP analysis and direct sequencing. (2) The
      distribution of polymorphic locus of short tandem repeat (STR) and variable
      number tandem repeat (VNTR) was analyzed by PCR and denaturing gel
      electrophoresis. (3) The correlations between genotype and phenotype were studied
      by analysis of the matching rate between the expected and observed phenotypes.
      The predicted phenotype was determined on the basis of the sum of the assigned
      values of the two mutant alleles. RESULTS: (1) A total of 34 different mutations
      were detected with the relative frequency of 95% among 50 PKU patients. The
      prevalent mutations in this study were: R243Q (20%), EX6-96A > G (11%), Y356X
      (9%), and V399V (7%). The next common mutations were R111X (5%), R413P (5%),
      R252Q (3%) and A434D (3%). Thirty-four detected mutations were distributed
      throughout the whole PAH gene, except exon 1, 8 and 13. Exon 7 and 11, with the
      mutant rate 34% and 19% respectively, seemed to be the hot mutant areas/regions
      of PAH gene. (2) The minihaplotypes (STR/VNTR) of 34 mutations were identified in
      this research. The STR and VNTR showed 8 and 3 alleles, respectively. Among them,
      244 bp (44%) and 240 bp (34%) were the prevalent STR alleles. Meanwhile, the
      VNTR3 (83%) was the most common VNTR allele in PKU patients. (3) A better
      consistency (81.5%) between expected and observed phenotypes was revealed by
      analysis of correlation between genotype and phenotype. Especially in classic
      PKU, the consistency rate was up to 87.5%. CONCLUSION: (1) The frequency
      distribution of common PAH gene mutations in Beijing region was close to that of
      Tianjin and Yunnan regions, while it was different from that of Southern regions
      of China, such as Guangzhou, especially Taiwan. The PAH mutation with a highly
      heterogeneous trait was also demonstrated in this study. (2) STR and VNTR
      minihaplotype will prove helpful to trace the origins of PAH mutations and to
      analyze the genetic drift. However, the most minihaplotypes of the STR/VNTR are
      similar, so it is necessary to associate some other polymorphic loci with the
      STR/VNTR minihaplotype to analyze the different mutations. (3) The fact that a
      better consistency existed between phenotypes and genotype with most PKU patients
      suggested that the study of the genotype of PKU patients would be helpful to the
      individualized treatment and to genetic counseling for their families.

PMID- 19099686
TI  - [Noise exposure in level III NICU environment in Beijing region and effects of
      intervention measures].
AB  - OBJECTIVE: To study the source of noise in level III NICU in Beijing region,
      evaluate preliminary intervention measures, and improve the NICU environment by
      reducing the noise. METHOD: Noise measurements were performed in level III NICU
      of three hospitals (A, B and C) in Beijing region by dosimeter (B&K 2231,
      Denmark), during loud hours and quiet hours. In addition, the loud hours were
      divided into shift time, nursing time and operating time. "Quiet hours"
      represents the intervals among shift, nursing and operating time. The noise
      inside/outside incubator was recorded, measures to reduce the noise, including
      putting plastic foam in incubator, covering sheet and blanket outside incubator
      were taken, and an educational program was implemented for the staff to decrease
      noise in the NICU environment. RESULTS: Among the three hospitals, the average
      noise of was (62.60 +/- 2.33) dB during the loud time, and (55.80 +/- 2.61) dB
      during the quiet time, with a difference of 7 dB (P < 0.05). There was a
      significant decrease of 2.7 - 3.3 dB during shift time with the averages of A
      hospital (62.3 +/- 1.5) dB, B hospital (65.10 +/- 2.44) dB and C hospital (61.80
      +/- 1.91) dB (F = 9.57, P < 0.05 and P < 0.01), separately. There was a
      significant decrease of 3 dB during nursing time with the averages of A hospital
      (62.0 +/- 2.4) dB, B hospital (64.90 +/- 1.06) dB (P < 0.01), respectively, and
      2.5 - 3.0 dB during treatment time with the averages of A hospital (60.7 +/- 2.2)
      dB, B hospital (63.30 +/- 1.19) dB (P < 0.05), separately. After educating the
      staff in hospital A, there was a significant decrease of 4.7 dB from (61.70 +/-
      2.12) dB to (56.90 +/- 2.49) dB in the loud time (P < 0.01), no significant
      difference during quiet time from (55.0 +/- 1.7) dB to (53.90 +/- 0.88) dB (P >
      0.05). There was a significant decrease of 10 dB (P < 0.01) between the averages
      of inside of incubator (58.60 +/- 3.43) dB and outside of incubator (67.10 +/-
      1.87) dB; After installing foam material inside incubator with the average of
      (56.20 +/- 1.83) dB, there was a significant decrease of 2.8 dB (P < 0.01);
      covering sheet (in front and back) with the averages of (57.00 +/- 1.47) dB and
      (55.3 +/- 1.3) dB, respectively, and single or double blanket outside incubator
      (in the front and the back) noise value (54.50 +/- 1.33) dB, (54.10 +/- 1.15) dB
      and (54.70 +/- 0.63) dB and (54.10 +/- 1.14) dB, separately, there was a decrease
      of 1 - 4 dB (P < 0.05 and P < 0.01). CONCLUSION: The noise in level III NICU in
      Beijing region is much higher than that allowed by regulations in Europe and the
      USA. Staff behavior and the acoustical characteristics of the facility determine
      the level of noise; herein to staff behavior is the main cause. The level of
      noise can be lowered considerably by simply making the staff aware of the
      problem. At the same time, covering incubator and installing plastic foam
      material also significantly decreased the noise, the methods are simple, feasible
      and should be applied constantly.

PMID- 19099687
TI  - [Comparative analysis of the pathogens responsible for hospital acquired and
      community acquired late onset neonatal septicemia].
AB  - OBJECTIVE: Late onset neonatal septicemia (systemic infection after 72 hours of
      life) remains a major cause of neonatal morbidity and mortality. Early treatment
      with appropriate antibiotics is critical since infected infants can deteriorate
      rapidly. The aim of this study was to review the pathogens responsible for late
      onset neonatal septicemia (LONS) and their antimicrobial susceptibilities in
      order to guide the initial selection of appropriate antibiotics for infants with
      suspected LONS. METHODS: A retrospective chart review of all cases with LONS seen
      in the neonatal intensive care unit (NICU) of Yuying Children's Hospital of
      Wenzhou Medical College from January 1, 2002 to December 31, 2005 was conducted.
      All cases were selected based on the clinical presentation and at least one
      positive result of blood culture. The basic clinical characteristics and the
      results of blood culture and antimicrobial susceptibilities were analyzed.
      RESULTS: A total of 102 cases with LONS were identified. Among those 102 cases,
      80 were community acquired (infants admitted from home and the blood culture was
      done on admission) and 22 were hospital acquired (infants became sick while in
      the NICU and the blood culture was done prior to use of antibiotics). The
      clinical presentations were non-specific. Compared to the infants with community
      acquired LONS, infants with hospital acquired LONS were usually born more
      prematurely (mean gestational age 33 +/- 3 vs 39 +/- 2 wks, t = 2.255, P < 0.01),
      with lower weight (mean weight 1.79 +/- 0.70 vs 3.23 +/- 0.67 kg, t = 8.818, P <
      0.01) and with younger age (mean age 12 +/- 6 vs 16 +/- 7 days, t = 7.581, P <
      0.05). Of the 102 cases, a total of 103 strains of bacteria were isolated. Among
      the pathogenic bacteria isolated, the most common were coagulase-negative
      Staphylococcus (CoNS) (50/103, 48.5%), followed by Klebsiella pneumoniae (16/103,
      15.5%). The main pathogens for community acquired LONS were Staphylococcus
      species and Escherichia coli. The most important pathogen responsible for
      hospital acquired LONS was Klebsiella pneumoniae. Most (> 80%) of the
      Staphylococcus especially CoNS were resistant to common antibiotics such as
      penicillin, erythromycin and cefazolin. Significant numbers (6/9) of
      Staphylococcus aureus isolated were methicillin-resistant Staphylococcus aureus
      (MRSA). However, all of the Staphyloccus isolates were sensitive to vancomycin.
      Almost all (15/16) of the Klebsiella pneumoniae isolated were multi-drug
      resistant due to production of extended-spectrum beta-lactamases (ESBLs). They
      were sensitive only to a few antibiotics such as carbapenems, aminoglycosides and
      quinolones. There was also one strain of vancomycin-resistant Enterococcus (VRE).
      Furthermore, there was no a single case of late onset neonatal sepsis due to
      infection with group B Streptococcus (GBS). CONCLUSIONS: The clinical
      manifestations of late onset neonatal sepsis are usually non-specific. GBS is not
      a significant pathogen responsible for community acquired LONS in the Wenzhou
      area. There are increasing numbers of multi-drug resistant bacterial species
      isolated from the newborn infants with late onset neonatal septicemia, which is
      most likely due the non-restricted use of antibiotics in the hospitals as well as
      in the communities. A routine blood culture should be taken from any newborn
      infant who is suspected of LONS and empirical use of appropriate antibiotics
      should be initiated as soon as the blood specimen for culture has been drawn. To
      reduce the occurrence of multi-drug resistant bacteria, the use of antibiotics
      especially the third generation cephalosporins in neonates should be restricted
      as much as possible.

PMID- 19099688
TI  - [Clinical manifestations and epidemic factors of autumn-winter type scrub typhus
      in children from northern new endemic area].
AB  - OBJECTIVE: Scrub typhus is an infectious disease due to Orientia tsutsugamushi
      transmitted by infected chigger mites. Scrub typhus has long been recognized to
      occur in southern areas of China, but has recently been increasingly often
      reported from the north since the first case was reported in Mengyin County,
      Shandong Province in 1986. The key objectives of the present study were to
      investigate the clinical manifestations and epidemic factors of scrub typhus in
      children from the northern new natural foci. METHODS: The case records of 56
      children with scrub typhus who were admitted to the 5 hospitals of Fei County
      from September 1993 to January 2004 were reviewed. Orientia tsutsugamushi (Ot)
      was isolated from the cases. Based on ecological observations on the composition,
      seasonal fluctuation of animal hosts and chigger mites, Ot was isolated from
      rodents and chiggers. IgG antibodies to Ot was detected by IFA. Genotypes of the
      Ot isolates were also identified by nested PCR. RESULTS: Among 56 children scrub
      typhus cases, 46 were male, 10 were female; 96% exhibited typical eschars or
      ulcers, 100% cases had high fever, skin rashes were observed in 55 cases (98%),
      and regional lymphadenopathy occurred in 48 cases (86%). All cases came from
      countryside, and all had histories of exposure to the crop field. fifty-one serum
      samples of suspected patients with scrub typhus were collected, 48 were positive
      for antibodies to Ot. The serotypes were Gilliam types. The cases only appeared
      in September to December with the peak at mid and late October. Leptotrombidium
      (L.) scutellare was the most important vector causing scrub typhus in the foci.
      Apodemus (A.) agrarius was the main host animals of Ot in the crop field. Totally
      26 strains were isolated from patients, rodents, and chigger mites. The serotypes
      of 24 out of the 26 isolates were Gilliam types, while the genotypes of these
      isolates were Kawasaki types. The serotypes of the other 2 isolates were
      identical and both were Karp types. CONCLUSION: Children scrub typhus patients
      were frequently seen in the new natural foci of Shandong province. Exposure
      history, typical eschars or ulcers, and presence of IgG antibody were the
      important indexes to diagnose the disease.

PMID- 19099689
TI  - [Expression of monocyte chemotactic protein-1 in peripheral blood mononuclear
      cells of children with Kawasaki disease and its relation to coronary artery
      impairment].
AB  - OBJECTIVE: Kawasaki disease (KD) is a febrile illness of childhood. The etiology
      of KD remains unknown. Multiple theories exist, including an infectious etiology
      and an immunological abnormality. Cardiac involvement ranges from myocarditis and
      pericarditis in the acute stage to the development of coronary artery aneurysms
      later in the course. The present study aimed to explore the effect of monocyte
      chemotactic protein-1 (MCP-1) in Kawasaki disease and its relationship with
      damage to the coronary arteries during the development of KD. METHODS: Plasma MCP
      1 concentrations were measured by enzyme-linked immunosorbent assay (ELISA), and
      MCP-1 mRNA expression in peripheral blood mononuclear cells (PBMC) was measured
      by quantitative reverse transcriptase polymerase chain reaction (qRT-PCR) in
      comparison of three groups: 56 patients with KD, 60 age-matched patients with non
      infectious diseases, and 66 age-matched febrile patients with various diseases.
      RESULTS: Plasma MCP-1 concentration and MCP-1 mRNA expression in PBMC of patients
      with active KD [(409.55 +/- 97.42) pg/ml] and (1.97 +/- 0.77) were higher than
      those of control group. Plasma MCP-1 levels and MCP-1 mRNA expression of inactive
      KD group [(301.64 +/- 71.55) pg/ml] and (1.31 +/- 0.39) were significantly higher
      than those of non-infectious diseases patients. There was a marked increase in
      patients with inactive KD than those of non-infective patients, but there were no
      significant differences between inactive KD and febrile patients. Plasma MCP-1
      levels and MCP-1 mRNA expression were markedly increased in KD patients with
      coronary artery lesions than those in patients without coronary artery lesions.
      CONCLUSION: Plasma MCP-1 concentration and MCP-1 mRNA expression in PBMC were
      significantly increased in patients with KD, and they were higher in KD with
      coronary artery lesions. It indicates that MCP-1 may be a useful parameter for
      monitoring disease activity in patients with KD.

PMID- 19099690
TI  - [Risk factors of irritable bowel syndrome in adolescents in China].
AB  - OBJECTIVE: To explore the risk factors for irritable bowel syndrome (IBS) among
      school adolescents in China. METHOD: A stratified, randomized study by cluster
      sampling was conducted, which recruited 51,956 students from high and primary
      schools in Chinese cities. All students were requested to fill in a
      questionnaire. RESULT: (1) Factors including class (odds ratio 1.12), excessive
      intake of pepper (odds ratio 1.17), fried (odds ratio 1.08) and starch-based
      foods (odds ratio 1.06), gastrointestinal tract infection (odds ratio 2.66),
      abuse of analgesic (odds ratio 1.49), inheritance (odds ratio 1.83), fatigue
      (odds ratio 1.32) and repression (odds ratio 1.45) were significantly associated
      with the presence of IBS (P < 0.05). High protein food (odds ratio 0.90) was a
      protective factor. CONCLUSION: Different food intake, gastrointestinal tract
      infection, abuse of analgesic, inheritance and psychological factors might be
      related to development of IBS in the students of the cities involved in this
      study.

PMID- 19099691
TI  - [Effect of p21 gene transfection mediated by replication deficient adenovirus on
      the pulmonary hypertensive rat model].
AB  - OBJECTIVE: To investigate the feasibility of transferring p21 gene into lung
      tissue with recombinant adenovirus with full-length cDNA of p21 inserted in the
      Wistar rat model of pulmonary hypertension (PAH) induced by left-to-right shunt,
      study the expression of the desired gene in vivo, find if overexpression of
      desired gene can inhibit pulmonary hypertension. METHODS: With full-length cDNA
      of p21 transfected HEK293 cells with clonfectin, and was packed, amplified in
      order to obtain the high-titer recombinant adenovirus (AdCMV-p21). The infection
      titer was determined by TCID50 method and was diluted into 1.67 x 10(8) pfu/L.
      Wistar rats were randomly allocated to control group (n = 10), model group (n =
      15), test group (n = 10) and test control group (n = 10). In model group and test
      group left-to-right shunt pulmonary hypertension was developed by using cuff
      technique. AdCMV-p21 was transfected into test group and test control group using
      tracheal inhalation. The mPAP, mRVP and RVHI were measured and compared between
      every two groups. The left lung was immunohistochemically stained to observe the
      result of transfection. The right lung was HE stained to observe morphological
      changes in arteria pulmonalis and calculate WT%. RESULTS: The mRVP, mPAP and WT%
      in model group and test group were significantly higher than those in control (P
      < 0.05), which suggested that the rat model of PAH was established successfully.
      Brown spots in the nucleus of VSMCs of pulmonary artery were seen in test group
      and test control group, which indicated that AdCMV-p21 was transfected
      successfully. The rate of transfected cells in test group was (42.8 +/- 11.6)%,
      which was equal to that of test control group (P > 0.05). In test group, the mPAP
      was (20.06 +/- 3.40) mm Hg (1 mm Hg = 0.133 kPa), mRVP was (22.53 +/- 2.53) mm
      Hg, WT% was (30.8 +/- 3.5)%, which were significantly lower than those in model
      group (P < 0.05), but higher than those in control group and test control group
      (P < 0.05). CONCLUSION: The recombinant adenovirus could successfully carry p21
      and transfect the lung tissue of PAH rat model, and full expression of p21. p21
      gene could inhibit the development of PAH.

PMID- 19099692
TI  - [Recurrent pneumonia in children: underlying causes, clinical characteristics and
      diagnostic methods].

PMID- 19099693
TI  - [Effect of bronchoalveolar lavage in therapy of mycoplasmal pneumonia with
      atelectasis in children].

PMID- 19099694
TI  - [Diagnostic value of nerve conduction function and F wave in children with lower
      limbs paralysis].

PMID- 19099695
TI  - [Castleman disease with paraneoplastic pemphigus in a child].

PMID- 19099696
TI  - [Childhood acute lymphoblastic leukemia presenting with hypercalcemia as first
      manifestation at initial onset, report of one case].

PMID- 19099697
TI  - [Treatment of a parabiotic infant with extracorporeal membrane oxygenation after
      commissurotomy].

PMID- 19099698
TI  - [Progresses in studies on gastrointestinal lesions in severe infections and
      septic shock].

PMID- 19099699
TI  - [Progress in molecular genetics in severe myoclonic epilepsy of infancy].

PMID- 19099701
TI  - [Introduction of solid foods to infants: a worldwide overview].

PMID- 19099700
TI  - [Correctly understand vitamin D deficient rickets].

PMID- 19099702
TI  - [Semi-solid food feeding is a non-abolishable biological period of human being
      development].

PMID- 19099703
TI  - [A national epidemiological survey on obesity of children under 7 years of age in
      nine cities of China, 2006].
AB  - OBJECTIVE: To examine the epidemiological features of prevalence and influencing
      factors on obesity of Chinese children from 1 month to 7 years of age in nine
      cities. METHODS: Stratified-clustered-random sampling was used, and the sampling
      size was 112 945 persons. Overweight and obesity were defined by the weight for
      height of NCSH/WHO reference, being over 10% as overweight and over 20% as
      obesity. The normal children were matched with obese children by region, gender,
      age and height in the case-control designs,and the data were analyzed by multiple
      conditional Logistic regression model. RESULTS: (1) The overall prevalence of
      overweight was 6.25%, 6.59% for boys and 5.88% for girls. The overall prevalence
      of obesity was 3.19%, 3.82% for boys and 2.48% for girls. The prevalence of
      obesity in different age groups was significantly different, 1.86% for 1 month to
      1 year old, lower for 1 to 3 years old, higher again after 3 years of age and
      reached 7.02% for 6 - 7 years of age. There was a significant regional difference
      in prevalence, which in the central (3.97%) and northern (3.21%) regions was
      higher than that in the south (2.47%). Most of the obese children belonged to
      mild obesity. Severe obesity occurred mainly after 3 years of age, and the
      prevalence of severe obesity for boys was significantly higher than the girls, in
      the northern part it was higher than those in the other two parts. (2) As
      compared with the survey data in 1986 and 1996, the prevalence of obesity
      increased by 2.78 times in the past 20 years, and the annual incremental rate was
      6.9%. The prevalence of obesity increased rapidly after 4 years of age and
      significant gender difference was seen. The higher prevalence shifted from the
      north to the central part of China. (3) Results of the Logistic regression
      indicated that appetite, eating speed, high maternal and paternal BMI, child
      caretaker, mode of delivery, main style of the outdoor activities, hours of
      watching TV, birth weight and duration of night time sleep were significantly
      related to obesity. CONCLUSION: (1) During the past 20 years the prevalence of
      child obesity showed a fast increasing trend in China. Degrees of the increasing
      trend differed across gender and age groups and regions. Effective strategies for
      intervention on population should be stipulated. (2) Good appetite, fast eating,
      high BMI of parents, caesarean birth, high birth-weight and excess hours of
      watching TV were possibly associated with increased risk of obesity in childhood,
      and those children looked after by their parents, medium intensity outdoor
      exercise and sufficient night sleep were associated with decreased risk of
      obesity.

PMID- 19099704
TI  - [National epidemiological survey on childhood obesity, 2006].
AB  - OBJECTIVE: The purpose of the 3rd national survey on childhood obesity was
      conducted not only to understand the present status and trends of childhood
      obesity in China since the last survey conducted 10 years ago, but also to reveal
      the health status of preschool children at nutrition transit period and to
      evaluate the efficacy and sensitivity of cited reference population, criteria and
      cut-off point of body mass index (BMI), adiposity rebound age, waist/hip ratio
      and other parameters relevant to the diagnosis of obesity made by the national
      task force on childhood obesity of China (NTFCOC). METHODS: A total of 84,766
      children aged 0 - 7 years were recruited in the survey by the random cluster
      sampling which represented a 1, 414, 220 children's population from 11 cities
      covered north, central, south and west regions of China. The criteria of
      screening overweight/obesity was more than 1 Z-score/2 Z-score of the medium of
      reference value of weight for height made by WHO. Length-height/weight for all
      subjects and waist/hip/thigh circumference and blood pressure data for children 3
      - 6 years of age were measured. The prevalence of overweight and obesity,
      overweight-obesity ratio, adiposity rebound age and BMI were calculated. The
      enumeration and measurement data were statistically managed by chi-square test
      and T-test, respectively using SPSS version 12.0 and the significance level was
      0.05. RESULTS: (1) The prevalence of obesity and overweight was 7.2% and 19.8%
      for all; 8.9% and 22.2% for boys, and 5.3% and 17.0% for girls, respectively,
      which is 3.6/4.7 times higher than that of 1996 respectively, the annual increase
      rate of obesity and overweight was in average 156% and 52%, respectively. The
      distribution pattern of prevalence of overweight and obesity in geographic areas
      and gender was that the northern regions had higher prevalence than the west and
      the central regions and the prevalence in boys was higher than in girls. The
      obesity/overweight ratio (OOR) was still at a high risk level. (2) BMI at 1 month
      after birth was higher than 16.5, then increased to the top of 17.8 at 1 year of
      age and decreased to the bottom of 15.7 at 5.5 years of age and increased a
      little since then. It was never higher than 18 of diagnosis point of obesity
      during the preschool age period. (3) The adiposity rebound age was 5.5 years of
      age in this study and delayed half a year as compared with that seen in 1999. The
      adiposity rebound ratio at first half year after birth (ARR1) was 0.56 and 0.97
      at second half year after birth (ARR2) which is an acceptable level according to
      the cut-off point made by NTFCOC and lower than the level obtained 10 years ago.
      (4) The pseudo-overweight phenomenon can be seen in the western regions which was
      derived from linear growth retardation and showed that both the malnutrition and
      obesity are a health problem in the poverty and maintain area of the western
      regions.(5) The 12.9% of obese children who's blood pressure was higher than 95th
      percentile of reference value and 17.2% of them had a waist/hip ratio higher than
      1.0 which is a warning point for the risk factor of CHD made by the NTFCOC. (6)
      The data showed that all the reference population and it's cut-off point for BMI,
      adiposity rebound age/ratio, waist/hip ratio etc. made by NTFCOC is valuable,
      reliable and practicable. CONCLUSION: The prevalence of childhood obesity and
      high blood pressure in obese children has been increased sharply during the
      recent 10 years, which is a out of control and a severe hazard to obese children.
      The early prevention and management of childhood obesity is urgently needed.

PMID- 19099705
TI  - [Sleep habits and sleep disturbance in school-age children of China].
AB  - OBJECTIVE: To survey the sleep habits (bedtime, wake time), sleep duration, and
      sleep problems in school-age children of China. METHOD: From November to
      December, 2005, a total of 19,299 school-age children from 55 elementary schools
      of 9 cities entered the study by a cross-sectional survey. A parent-administered
      questionnaire and the Chinese version of the Children's Sleep Habits
      Questionnaire were applied to investigate children's sociodemographic
      characteristics and sleep behaviors, respectively. RESULTS: The mean sleep
      duration was 9 hours and 10 minutes (9:10, SD:48 min) during the weekdays and
      9:48 (SD: 63 min) during the weekends. In about 71.4% and 41.8% school-aged
      children the sleep duration per day did not reach the lowest criterion of 10
      hours recommended by the Ministry of Education of China during weekdays and
      weekends, respectively. Sleep problems were common with prevalence ranging from
      14.5% for sleep-disordered breathing to 75.3% for daytime sleepiness. Parasomnia
      (chi(2) = 13.76, P < 0.01) and sleep-disordered breathing (chi(2) = 119.83, P <
      0.01) were more prevalent in boys than in girls; however, sleep anxiety was more
      prevalent in girls than in boys (chi(2) = 19.42, P < 0.01). Except for night
      waking, other types of sleep problems were significantly associated with age.
      CONCLUSIONS: Inadequate sleep duration and sleep problems prevail among school
      age children, which indicates that children's sleep health may be a major public
      health concern in China.

PMID- 19099706
TI  - [Recommendation for prevention and treatment of rickets of vitamin D deficiency
      in childhood].

PMID- 19099707
TI  - [Summary of the symposium on recommendation for prevention and treatment of
      vitamin D deficient rickets in childhood].

PMID- 19099708
TI  - [Review of progresses in prevention and treatment of vitamin D deficiency and
      rickets in childhood].

PMID- 19099709
TI  - [Detection of fusion genes in childhood acute lymphoblastic leukemia by using
      oligonucleotide microarrays approach].
AB  - OBJECTIVE: To evaluate the possibility of applying oligonucleotide microarrays
      for detection of the fusion genes in childhood acute lymphoblastic leukemia
      (ALL). METHODS: To detect five types of fusion genes emerging frequently in
      childhood ALL including TEL/AML1, E2A/PBX1, BCR/ABLp190, BCR/ABLp210, MLL/AF4,
      probes were designed, synthesized and spotted on the chemical-material-coated
      glass plates in array. The total RNAs were extracted from patients' bone marrow
      or peripheral blood cells at the beginning of diagnosis, analyzed by multiplex
      nested reverse-transcription-polymerase chain reaction (RT-PCR), and labeled by
      fluorescein. The products of RT-PCR were hybridized with microarray in order to
      detect specific types of fusion genes in leukemia cells. RESULTS: Distinctive
      hybridization signals were obtained for internal positive control and specific
      types of fusion genes. TEL/AML1 gene was found positive in 2 of the 36 cases,
      E2A/PBX1 gene in 3, BCR/ABLp190 gene in 2, BCR/ ABLp210 gene in one, and MLL/ AF4
      gene in one. The results of the microarray and RT-PCR were consistent.
      CONCLUSION: The microarray-based assay could screen 5 types of chromosome
      structural aberrations and the splice variants at the same time. It can provide
      reliable and helpful information for patient stratification, evaluation of
      therapeutic effects and prediction of prognosis in childhood ALL, although there
      are both advantages and disadvantages in applying this new method.

PMID- 19099710
TI  - [Investigation on individualized adjustment of target range of high-dose
      methotrexate].
AB  - OBJECTIVE: To explore the way of individualized adjustment of target range of
      each high-dose methotrexate (MTX) 24 hours infusion to treat acute lymphoblastic
      leukemia in children. METHODS: Twenty-four children and 105 infusions were
      included in the study. According to 1 h and 6 h plasma MTX concentrations after
      infusion, based on established high-dose MTX population pharmacokinetics model,
      the course predicted value of drug concentration at steady state (C(SS)) was
      calculated. MTX infusion rate and dosage was adjusted 8 h after the start
      according to the predicted value of C(SS). Then MTX concentration at 23 h (actual
      value of C(SS)) was measured. RESULTS: To achieve the target range of C(SS),
      adjustments of MTX dosage were required in 17 (71%) patients. Adjustments of MTX
      dosage were required in 45 (43%) infusions, the dose was increased in 42
      infusions and decreased in 3 infusions. There were 29 infusions of high-dose MTX
      during consolidation therapy (after remission induction therapy). Among them, 16
      infusions had increased dosage, and 1 infusion had decreased dosage. There were
      76 infusions during maintenance therapy. Among them, 26 infusions increased
      dosage, and 2 infusions decreased dosage. Overall 95 (90%) infusions achieved the
      target range of C(SS), while in 8 infusions the doses were lower than the target
      range in 2 infusions the doses were higher than the target range. If there had
      been no adjustments, only 74 (70%) infusions could have achieved the target
      range. Adjustments of MTX dosage, compared with no adjustments, could remarkably
      enhance the rate of achieving the target range of C(SS) (chi(2) = 13.366, P =
      0.000). Among 60 infusions of no adjustments, the actual values of C(SS) were
      well correlated with the predicted values of C(SS) (r = 0.487, P = 0.000), and
      the actual values of C(SS) were also correlated with the 6 h plasma MTX
      concentrations after infusions (r = 0.389, P = 0.002). The actual values of total
      clearance (CL) of MTX of 105 infusions were 7.01 +/- 2.06 L/(m(2).h). Inter
      courses variability in CL was up to 4.4-fold. Intra-patient variability in CL was
      up to 2.9-fold. Predisposing factors that correlated with decreased CL of MTX
      were old age, heavy body weight, low blood phosphate, high blood bilirubin and
      infusions during maintenance therapy (P < 0.05). CONCLUSIONS: High-dose
      methotrexate chemotherapy needed individualized adjustment, as inter-courses
      variability of CL was up to 4.4-fold among 105 infusions. According to 1 h and 6
      h plasma MTX concentrations after infusion, adjusting MTX infusion rate and
      dosage, overall 90% infusions achieved the target range of C(SS). High-dose MTX
      infusions during consolidation therapy needed individualized adjustment of target
      range more.

PMID- 19099711
TI  - [Clinical study of 40 children with Burkitt's and Burkitt-like lymphoma].
AB  - OBJECTIVE: To summarize the histological and clinical characteristics of 40 cases
      with Burkitt's and Burkitt-like lymphoma in children, to evaluate the effects of
      treatment with international regimen, and to explore the treatment-related
      complications and prognostic factors. METHODS: Forty patients with Burkitt's and
      Burkitt-like lymphoma were registered in Beijing Children Hospital from Feb 2003
      to Apr 2006. The diagnosis was confirmed by histology and immunohistochemistry of
      biopsy, and clinical staging by the examination of imaging, cerebrospinal fluid
      and bone marrow based on St. Jude system. Intensive, short-term chemotherapy
      witch was modified from LMB89 protocol was given to the patients. RESULTS: Of the
      40 patients, 30 were diagnosed as Burkitt's lymphoma (BL) and 10 as Burkitt-like
      lymphoma (BLL). Antibody against Epstein-Barr virus (EBV-Ab) was positive in 19
      cases at diagnosis, only 7 of the patients were positive for EBER. Thirty-three
      of the cases were male and 7 female (M:F = 4.7:1); the median age was 6 years 9
      months. The most frequently seen clinical characteristics were abdominal masses
      and surgical abdomen. Nine cases were at stage I - II and 31 cases at stage III -
      IV at diagnosis; CNS was involved in 4 cases and bone marrow in 2 cases. The
      courses of treatment were approximately 2 - 8 months. All the patients were
      followed up, the median follow-up period was 22.6 months. After chemotherapy, 35
      patients (88.7%) were still alive during the one-year follow-up. The 3-year event
      free survival (EFS) rate was 81.8%. Major toxicity was myelosuppression and
      mucositis. Stage III to IV of myelosuppression occurred in the most patients with
      unresected tumor and CNS-involvement. Of 5 patients who died, 2 died of
      infection, 2 died of lymphoma progression during chemotherapy, and 1 died of
      relapse. CONCLUSION: Burkitt's and Burkitt-like lymphoma are the most common NHL
      in children with rapid clinical process. Outcome was greatly improved by current
      intensive, short-term chemotherapy regimen, the 3-year EFS was 81.8% including
      the patients who were in advanced stage. Childhood lymphoma with short clinical
      history, stage IV and residual disease after 3 months of therapy are associated
      with poor prognosis.

PMID- 19099712
TI  - [A Chinese girl with fibrodysplasia ossificans progressiva caused by a de novo
      mutation R206H in ACVR1 gene].
AB  - OBJECTIVE: Fibrodysplasia ossificans progressiva (FOP) is a rare autosomal
      dominant inherited disease caused by mutations of ACVR1 gene and can be inherited
      from either mother or father. FOP is characterized by the presence of
      malformations of the big toes and of progressive extra-skeletal ossification.
      Direct sequence analyses of genomic DNA have demonstrated that there is an
      identical single nucleotide substitution (c617G-->A, R206H) in the glycine-serine
      (GS) activation domain of ACVR1 gene, responsible for all affected individuals
      reported so far. We report a Chinese girl with typical FOP characteristics, in
      whom the same mutation in ACVR1 was identified. METHODS: Clinical diagnosis was
      based on physical examination, radiological findings, and biochemical tests. For
      mutation detection, peripheral blood was obtained with informed consent from the
      patient and the parents. Genomic DNA was extracted from peripheral blood using
      standard method. Exon 4 of ACVR1 was amplified by polymerase chain reaction
      (PCR), and the PCR products were subjected to automatic DNA sequencing. RESULTS:
      The affected girl is 3-year-old and showed typical clinical manifestations of
      FOP. She had malformations of the halluces at birth and subsequently progressive
      extra-skeletal ossification developed at the age of 8 - 9 months. Then, she
      gradually developed stiffness of the knee joint and neck but remained ambulant.
      Radiographic changes were observable, e.g., the extra-skeletal ossification was
      found at cervical spine. Her mother has congenital malformations of the halluces,
      but had no postnatal progressive extra-skeletal ossification. Her father and
      other family members are normal. With direct sequencing of the PCR products, a G
      to A substitution at c617 of ACVR1 (R206H) was detected in the patient only but
      not in her parents. Paternity analysis suggested that it is a de novo mutation.
      CONCLUSION: This is the first case reported in a Chinese patient with FOP in the
      mainland of China, which was confirmed by direct sequencing. Although sporadic
      cases of FOP have been reported in diverse geographic and ethnic group, the
      mutations of ACVR1 c617 (R206H) are identical up to now. The presence of mutation
      hot spot facilitates molecular diagnosis in clinical practice. Genetic detection
      is important for FOP patients to avoid misdiagnosis and further damages,
      including those from medical intervention.

PMID- 19099713
TI  - [Soft-tissue pyogenic infection in neonates caused by Staphylococcus aureus
      carrying Panton-Valentine leukocidin genes].
AB  - OBJECTIVE: To investigate the pathogen causing soft-tissue pyogenic infection in
      neonate. METHODS: The isolates of Staphylococcus aureus were obtained from liquor
      puris and blood by routine method. The Automated Microbiology Analyzer was used
      for identification and antimicrobial susceptibility test of the isolates. Panton
      Valentine leukocidin (PVL) genes were determined by multiplex PCR in the isolates
      of Staphylococcus aureus. Multilocus sequence typing (MLST) was used to determine
      the sequence types (STs) of the isolates. The genotypes of SCCmec were also
      determined by another multiplex PCR in the isolates of methicillin-resistant
      Staphylococcus aureus (MRSA). RESULTS: In 3 cases of neonate with soft-tissue
      pyogenic infection, 2 strains of Staphylococcus aureus isolated from liquor puris
      in 2 cases. 2 strains of Staphylococcus aureus were isolated from liquor puris
      and blood from another case. All 4 isolates were methicillin-resistant
      Staphylococcus aureus (MRSA) strains carrying PVL genes. Their SCCmec types were
      SCCmec IIIA. The STs of 4 isolates were ST88. The antimicrobial-resistance
      profile of the isolates were the same except erythromycin. CONCLUSION: Soft
      tissue pyogenic infection in the 3 neonates was caused by the same clone of MRSA
      carrying PVL genes.

PMID- 19099714
TI  - [A randomized controlled study on the efficacy of inhaled nitric oxide in
      treatment of neonates with meconium aspiration syndrome].
AB  - OBJECTIVE: Meconium aspiration syndrome (MAS) is a disease of the term and near
      term infant that is associated with considerable respiratory morbidity. The
      purpose of this study was to investigate effects of inhaled nitric oxide (iNO) in
      oxygenation and outcome of newborns with MAS. METHODS: Eligible patients
      diagnosed as severe MAS admitted consecutively to the neonatal intensive care
      unit (NICU) of Hebei Children's Hospital from January 2004 to June 2006 were
      included in the study. The patients with an oxygenation index (OI) > or = 15 were
      randomized in a nonblinded manner to receive either iNO (NO group, n = 21) or no
      NO (control group, n = 25). Patients with an OI > or = 15 after enrollment were
      treated with iNO at 15 ppm initially. The response to iNO was assessed according
      to the increase in arterial PaO(2) and oxygen saturation (SpO(2)) after exposure
      to the starting concentration for 60 minutes. A response of 10 mm Hg (1 mm Hg =
      0.133 kPa) increase in PaO(2) and a 10% increase in SpO(2) was assessed
      responsive to iNO. All patients were treated in the same neonatal unit and
      received the same standard therapy throughout the study period. Arterial blood
      gas tensions, pulmonary arterial pressure and systemic arterial blood pressures
      were recorded at baseline, 1 hour, and 24 hours in all patients. Methemoglobin
      levels were obtained at 12 - 24 hours after inhaled NO treatment. Parameters of
      fraction of inspired oxygen (FiO(2)), OI, mortality, ventilation time, and
      incidence of intraventricular hemorrhage (IVH, grade III-IV) were recorded.
      Informed consent was obtained from parents before enrollment. The protocol and
      the informed consent forms were approved by the ethic committee of the hospital
      before patient enrollment. RESULTS: There was no significant difference in
      gestational age, birth weight, gender ratio, age at admission in hours, c-section
      delivery between the two groups, and no significant difference was found in
      respiratory mechanics parameters between the two groups at baseline. The duration
      of iNO was 34.90 +/- 16.41 hours. At the beginning of the treatment, no
      significant differences were detected in the OI and PAP between the two groups.
      One hour later, OI and PAP of NO group decreased significantly (OI, F = 35.27, P
      < 0.01, PAP, F = 24.30, P < 0.01), while in control group the difference was not
      found until 24 hours (OI, F = 20.16, P < 0.01, PAP, F = 101.22, P < 0.01). There
      were significant differences in PAP at 1, 24 hours between the two groups (1 h, t
      = 2.41, P < 0.05; 24 h, t = 3.11, P < 0.01). The methemoglobin levels were
      normal. Compared to the controls, hospital stay (t = 2.86, P < 0.05), duration of
      the need for oxygen supplement (t = 2.53, P < 0.05) and ventilation time were
      shorter (t = 2.41, P < 0.05), whereas mortality (chi(2) = 0.21, P > 0.05) and
      incidence of IVH (chi(2) = 0.00, P > 0.05) were not significantly different
      between the groups. CONCLUSIONS: iNO could effectively improve the oxygenation
      and shorten the ventilation time and hospital stay without augmentation of risk
      of IVH and pneumothorax in these neonatal patients.

PMID- 19099715
TI  - [Temporal expression and significance of caspase-3 and interleukin-8 in the lungs
      of preterm rats exposed to hyperoxia].
AB  - OBJECTIVE: To explore the temporal expression and significance of Caspase-3 and
      interleukin-8 (IL-8) in hyperoxia-induced lung injury in preterm rats. METHODS:
      Two-day-old Sprague-Dawley preterm rats were randomly divided into Air group and
      Hyperoxia group (each rats in each group). Rats in the Hyperoxia group were
      exposed to 85% O(2), while rats in the Air group were exposed to air. The rats in
      each group were sacrificed at 1, 4, 7, 14 and 21 days after exposure (8 rats at
      each time point), and lung tissues were collected. Pathomorphology of lungs was
      observed by hematoxylin-eosine staining. The contents of IL-8 in the homogenate
      of lungs were detected using ELISA. The expression of Caspase-3 was detected by
      immunohistochemistry and Western blot. RESULTS: (1) Lung histopathology: after
      hyperoxia exposure 1 day, no significant effects on alveoli were found; but on
      days 4 and 7, alveolitis appeared: there were necrotic abscission cells in
      alveolar space, increased inflammatory cells infiltration, lung interstitial
      edema; on days 14 and 21, lung structure derangement, decreased number of
      alveoli, simplified and vesicular lung structure, all of which showed the
      retardation of alveolar formation. (2) the contents of IL-8 in the homogenate of
      lungs had no significant change on day 1 but increased significantly on days 4, 7
      and 14 compared with air control group (P < 0.01 for all). (3)
      Immunohistochemistry detected the expression of Caspase-3 in the lung: the
      intensity of Caspase-3 expression increased significantly on days 4, 7 and 14
      compared with air control group (P < 0.01). (4) Western blotting detected the
      expression of caspase-3 in the lung: the pattern of dynamic expression of Caspase
      3 was similar to the results of immunohistochemistry. CONCLUSIONS: Both apoptosis
      and necrosis contribute to cell death during hyperoxia. Apoptosis and necrosis
      may both play an important role in hyperoxia-induced lung injury in preterm rats.

PMID- 19099716
TI  - [A girl with medullary sponge kidney and distal renal tubular acidosis was
      chronically misdiagnosed as rickets].

PMID- 19099717
TI  - [Two cases of rare abnormality karyotype of chromosome in one family].

PMID- 19099718
TI  - [A case with hand, foot and mouth disease associated with central nervous
      symptoms related to enterovirus 71 in Beijing].

PMID- 19099719
TI  - [Infantile kala-azar: report of a case].

PMID- 19099721
TI  - [Pay much attention to improving awareness of clinical nutrition among pediatric
      gastroenterologists in China].

PMID- 19099720
TI  - [Menkes disease in a child].

PMID- 19099722
TI  - [Serum gastrin levels and clinical conditions in response to early minimal
      feeding in premature infants].
AB  - OBJECTIVE: To study serum gastrin levels in response to early minimal feeding in
      premature infants and evaluate the clinical effect of early minimal feeding.
      METHODS: Premature infants with critical score < or = 90 were randomly assigned
      into two groups: early minimal feeding group (n = 48), non-early minimal feeding
      group (n = 47). Other premature infants (n = 30) without any complications
      (critical score > 90) were assigned as normal control group. The premature
      infants in normal control group were fed with water at 6 h after birth, 1 - 2
      ml/kg every time, after once or twice, they were fed with formula, increasing in
      the amount of formula gradually, until adequate. The premature infants in early
      minimal feeding group were fed with formula within 72 h after birth, 0.5 - 1
      ml/kg, once every 3 h, the amount of formula was increased gradually, until
      adequate. The premature infants without early minimal feeding were not fed with
      formula until the illness was stable, the amount of formula was increased
      gradually until adequate. Situation of gastrointestinal feeding tolerance, growth
      and development, and clinical symptoms were observed and recorded for the three
      groups. Serum gastrin levels were monitored at 1, 3, 7 day after birth by
      radioimmunoassay. RESULTS: Serum gastrin concentrations in the three groups
      elevated from 1 to 7 days. In early minimal feeding group [(82.4 +/- 24.5) ng/L]
      and non-early minimal feeding group [(87.0 +/- 40.2) ng/L], the concentrations
      were significantly higher than those in normal control group [(66.4 +/- 19.7)
      ng/L] at day 1 (F = 3.36, P < 0.05). At day 3 and 7, the concentrations in early
      minimal feeding group [(96.3 +/- 14.6) ng/L, (113.0 +/- 16.5) ng/L] were
      significantly higher than those in non-early minimal feeding group [(73.9 +/-
      13.5) ng/L, (92.4 +/- 12.2) ng/L] (P < 0.05). There were significant differences
      among the three groups in infants with feeding intolerance (2/30, 5/48, 14/47),
      the period reached full enteral feeding [(20.6 +/- 5.7) d, (27.8 +/- 6.1) d,
      (39.5 +/- 4.7) d], and in number of hospital day [(29.0 +/- 4.6) d, (39.0 +/-
      4.8) d, (48.0 +/- 5.6) d] (P < 0.05). There were significant differences between
      early minimal feeding group and non-early minimal feeding group in the weight
      gain three and four weeks after birth [(19.1 +/- 2.4) g/d, (11.9 +/- 3.3) g/d],
      the period reached birthweight [(19.8 +/- 4.2) d, (25.2 +/- 5.1) d] (P < 0.05).
      There were no significant difference among the three groups in the weight gain in
      one and two weeks after birth [(5.9 +/- 2.9) g/d vs. (5.0 +/- 2.1) g/d], the
      numbers of premature infants with infection, anemia, apnea, or hypoglycemia.
      CONCLUSION: Early minimal feeding in premature infants leads to secretion of
      gastrin, promotes the development of gastrointestine and may not be associated
      with occurrence of complications.

PMID- 19099723
TI  - [Treatment of congenital hypertrophic pyloric stenosis with endoscopic
      pyloromyotomy].
AB  - OBJECTIVE: To evaluate the effect of the treatment of congenital hypertrophic
      pyloric stenosis (CHPS) with endoscopic pyloromyotomy. METHOD: Nine consecutive
      infants (7 boys, 2 girls; age range 26 - 70 days; weight range 2.65 - 6.10 kg),
      with a diagnosis of CHPS according to typical clinical manifestations,
      transabdominal ultrasound (US), gastroenterography and gastroscope. All the cases
      had accompanying malnutrition, anaemia, metabolic alkalosis, and some were
      complicated with congenital heart disease. In gastroscope operating room, all the
      patients were given pentobarbital and midazolam intravenously. A gastroscope with
      an outer diameter of 5.9 mm was passed through mouth, stomach, pylorus to the
      descending segment of duodenum. Under gastroscopy, two incisions were made along
      the anterior and posterior wall of pylorus from the duodenal bulb to the antrum
      by using endoscopic electrosurgical needle knife and an arch sphincter sarcosome.
      Incisions were deepened by 2 to 3 procedures until the longitudinal muscle was
      exposed, about 2 to 4 mm according to transabdominal US performed before
      operation. The incision depth was 2 - 3 mm if pylorus wall was 4 - 6 mm in
      thickness; or 3 - 4 mm when the wall was thicker than 6 mm. RESULT: The endoscope
      was easily passed through the pylorus to the duodenum post-operation. The
      transabdominal US and gastroenterography showed that liquid easily flew through
      pylorus. All patients were able to have regular feeding about 2 to 10 hours after
      the operation. Vomiting in all patients was significantly decreased in frequency
      and amount, and in 8 infants vomiting stopped within 1 week, in one case it did
      not stop until 1 month after the treatment. Some cases showed slight adverse
      reaction, no perforation or massive haemorrhage in stomach or intestines occurred
      in any of the patients during and post-operation. Eight infants were doing well
      at follow-up (range 2 to 9 months). One girl had recurred vomiting at normal
      feeding after a period of 1 month postoperation without vomiting. This case was
      cured by second endoscopic pyloromyotomy. CONCLUSIONS: Endoscopic pyloromyotomy
      is effective, safe, simple, and offers several advantages: no need for open
      abdomen surgery, feeding can be initiated rapidly.

PMID- 19099724
TI  - [Effects of high-dose methotrexate therapy on intestinal bacterial flora in
      children with acute lymphoblastic leukemia].
AB  - OBJECTIVE: To investigate the effects of high-dose methotrexate (HDMTX) therapy
      on intestinal bacterial flora in children with acute lymphoblastic leukemia
      (ALL). METHODS: Thirty-six children with ALL of pre-and post-HDMTX therapy and 36
      control children were enrolled. The bacterial DNA in stool was extracted. The
      primers for Bacillus bifidus and Escherichia coli with the 16SrRNA/DNA sequence
      of bacteria were designed. The bacteria were identified through general PCR. The
      standard curve of both bacterial DNA was produced using a series of dilution of
      accurately quantified bacterial DNA. The unknown samples were measured by
      16SrRNA/DNA-targeted PCR. The amount of stool Bacillus bifidus and Escherichia
      coli among 36 control children and 36 children with ALL of pre- and post-HDMTX
      therapy were obtained by using the standard curves. RESULTS: Bacillus bifidus
      logarithmic absolute value of the first day before treatment, of third day after
      treatment, of seventh day after treatment in patients with ALL and the control
      was 7.24 +/- 0.33, 6.00 +/- 0.27, 6.59 +/- 0.33, and 9.49 +/- 0.41, respectively
      (P < 0.01). Escherichia coli logarithmic absolute value of the first day before
      treatment, of third day after treatment, of seventh day after treatment in
      patients with ALL and the control was 6.62 +/- 0.42, 5.96 +/- 0.42, 7.02 +/-
      0.41, and 7.52 +/- 0.43, respectively (P < 0.01). The logarithm of the amount of
      stool Bacillus bifidus and Escherichia coli in control group was higher in ALL
      group (F = 739.61, 88.67, P < 0.01). There were significant difference (P < 0.01)
      in the logarithm of the amount of stool Bacillus bifidus and Escherichia coli
      between pre-therapy and post-therapy group. The logarithm of the bacterium was
      very low on third day after treatment, but gradually increased on the seventh day
      after treatment. CONCLUSIONS: (1) HDMTX therapy has great effects on intestinal
      flora of Bacillus bifidus and Escherichia coli and significantly reduced the
      bacteria in children with ALL. (2) Probiotics had significantly decreased in ALL
      group than in control group.

PMID- 19099725
TI  - [Pathogenic effects of primary duodenogastric reflux on gastric mucosa of
      children].
AB  - OBJECTIVE: Duodenogastric reflux (DGR) is a reverse flow of duodenal juice into
      stomach through pylorus composed of bile acid, pancreatic secretion, and
      intestinal secretion. The increased entero-gastric reflux results in mucosal
      injury that may relate not only to reflux gastritis but also esophagitis, gastric
      ulcers, carcinoma of stomach and esophagus. However, the exact mechanisms of
      gastric mucosal damage caused by DGR are still unknown. The objective of the
      present study is to investigate the pathogenic effect of primary DGR on gastric
      mucosa in children, and to explore the correlation of DGR with clinical symptoms,
      Hp infection and intragastric acidity. METHOD: Totally 81 patients with upper
      gastrointestinal manifestations were enrolled and they were graded according to
      the symptom scores and underwent endoscopic, histological examinations and 24
      hour intra-gastric bilirubin was monitored with Bilitec 2000. Of the 81 cases, 51
      underwent the 24-hour intra-gastric pH monitoring by ambulatory pH recorder
      simultaneously. The total fraction time of bile reflux was considered as a marker
      to evaluate the severity of DGR. The total fraction time of bile reflux was
      compared between the patients with positive and negative results under endoscopy
      and histologically, respectively. The correlations of the total fraction time of
      bile reflux with clinical symptom score, Hp infection, intragastric acidity were
      analyzed respectively. RESULT: The total fraction time of bile reflux in the
      patients with hyperemia and yellow stain gastric antral mucosa under endoscopy
      was significantly higher than that without those changes [17.1% (0.5%
      approximately 53.2%) vs. 6.5% (0 approximately 58.6%), Z = -1.980, P < 0.05;
      19.8% (0.5% approximately 58.6%) vs. 8.8% (0 approximately 38.0%), Z = -2.956, P
      < 0.01 respectively]. Histologically, the cases with intestinal metaplasia had
      significantly higher total fraction time of bile reflux than in the cases without
      intestinal metaplasia [29.0% (1.9% approximately 58.6%) vs. 14.3% (0
      approximately 53.7%), Z = -2.026, P < 0.05], but no significant difference was
      found either between the cases with and without chronic inflammation (P > 0.05)
      or between the cases with and without active inflammation (P > 0.05). The
      severity of bile reflux was positively correlated with the score of abdominal
      distention (r = 0.258, P < 0.05), but no correlation with either the severity of
      intragastric acid (r = -0.124, P > 0.05), or Hp infection (r = 0.016, P > 0.05)
      was found. CONCLUSION: Primary DGR could cause gastric mucosal lesions manifested
      mainly as hyperemia and bile-stained gastric antral mucosa under endoscopy and
      the gastric antral intestinal metaplasia histologically in children. There was no
      significant correlation between DGR and gastric mucosal inflammatory
      infiltration. DGR had no relevance to Hp infection and intragastric acidity. We
      conclude that DGR is probably an independent etiological factor and might play a
      synergistic role in the pathogenesis of gastric mucosal lesions along with
      gastric acid and Hp infection.

PMID- 19099726
TI  - [Recommendations for blocking mother-to-infant transmission of hepatitis B
      virus].

PMID- 19099727
TI  - [Summary of the 7th national conference on pediatric GI diseases and infectious
      diseases and the 2nd national conference on pediatric clinical virology].

PMID- 19099728
TI  - [Noninvasive preoperative estimation of pulmonary vascular resistance of the
      patients waiting for two staged Fontan procedure].
AB  - OBJECTIVE: Noninvasive method for estimating the pulmonary vascular resistance
      (PVR) was used in patients waiting for two staged Fontan procedure to observe the
      relationship between estimated PVR and surgical results. METHODS: Thirty-three
      candidate patients for two staged Fontan procedures were randomly selected for
      this trial. Preoperative hemoglobin (HGB), hematocrit (HCT) and pulse oxygen
      saturation (SpO2) were measured. Estimated PVRs were then calculated by the
      regression equations. The cases were divided into three groups of low risk group
      with PVR less than 2.4 wood, high risk group with PVR between 2.4 to 3.2 wood,
      and extremely high risk group with PVR more than 3.2 wood. The incidences of
      postoperative low cardiac output and multi-organ failure were compared.
      Simultaneously, the cases without or with postoperative severe low cardiac output
      and multi-organ failure after operation were divided into two groups. The
      preoperative HGB, HCT and estimated PVR among the groups were analyzed. RESULTS:
      The rates of postoperative severe low cardiac output and multi-organ failure were
      10.0%, 32.4% and 63.6% for the patients of low, high and extremely high risk
      groups respectively. The difference was significant (P < 0.01). The preoperative
      HGB, HCT, SpO2 and PVR were all significantly different between the patients
      without or with postoperative severe low cardiac output and multi-organ failure.
      The PVR (HGB) were (2.53 +/- 0.56) wood and (3.24 +/- 0.58) wood respectively.
      The PVR (HCT) were (2.59 +/- 0.58) wood and (3.21 +/- 0.79) wood respectively.
      The PVR (SpO2) were (2.22 +/- 0.55) wood and (2.93 +/- 0.58) wood, respectively.
      The differences were all significant (t = 3.25, 2.52 and 3.33 respectively, P <
      0.01 or 0.05). CONCLUSIONS: Preoperative estimated PVRs calculated by HGB, HCT
      and SpO2 were comparable with the postoperative results. Thus, the invasive
      preoperative estimation of pulmonary vascular resistance could be a method in
      estimating the surgical indication and predicting the surgical result for two
      stage Fontan procedure.

PMID- 19099729
TI  - [Relationship between leukotrienes and clinical, pathological features of Henoch
      Schoenlein purpura nephritis in children].
AB  - OBJECTIVE: To investigate the role of leukotrienes (LTs) in the progress of
      children's Henoch-Schoenlein purpura (HSP) nephritis (HSPN), and to provide an
      experimental basis for clinical application of leukotrienes antagonists in
      treatment of HSPN. METHODS: The serum and urine samples were collected from 34
      patients with HSPN 18 of them received renal biopsy, 27 cases with HSP and 16
      healthy children as control. The level of LTB4 in the serum and urine was tested
      by enzyme-linked immunosorbent assay (ELISA) and LTE4 in urine in each group by
      enzyme immunoassay (EIA). The extent of expression of LTC4 synthase was detected
      by indirect immune fluorescence (IIF) in the renal tissue of 18 HSPN cases who
      received renal needle biopsy. Meanwhile, 3 cases with thin basement membrane
      nephropathy (TBMN) and 4 cases with simple hematuria were enrolled as controls.
      The results of pathological examination of the 4 cases with simple hematuria was
      normal by light microscope or electron microscope. At the same time, total urine
      protein in 24 hours was determined in 24 HSPN patients. RESULT: (1) The level of
      serum and urinary LTB4 in the children with HSPN was (1164.33 +/- 300.28) ng/L
      and (841.19 +/- 115.23) ng/L, respectively. The level of serum and urinary LTB4
      in those with HSP was (559.60 +/- 180.23) ng/L and (574.42 +/- 101.17) ng/L,
      respectively. The level of serum and urinary LTB4 in the control group was
      (211.95 +/- 67.72) ng/L and (227.33 +/- 76.12) ng/L, respectively. There was
      significant difference in the LTB4 level between HSPN group and HSP group (P <
      0.01) while there was statistically significant difference in the LTB4 level
      between HSPN group and control group (P < 0.01). The urinary LTE4 was (1252.31 +/
      251.62) ng/L, (805.93 +/- 185.52) ng/L and (149.51 +/- 33.66) ng/L for HSPN
      group, HSP group and control group, respectively, and the differences were
      significant (P < 0.01). (2) The increase of serum and urinary LTB4 and urinary
      LTE4 was closely relative to the severity of histopathological changes. (3) Serum
      and urinary LTB4, urinary LTE4 increased in parallel to the enhancement of urine
      protein in HSPN patients (P < 0.01 or P < 0.05). (4) Markedly significant
      difference of LTC4 synthase by IIF existed between HSPN groups and control group.
      CONCLUSION: LTs can promote the progress of children's HSPN. There is a close
      relationship between LTs expression in renal tissues, the pathological severity
      of HSPN and proteinuria.

PMID- 19099730
TI  - [Relationship between the expression of the genes encoding the key enzymes for
      cytarabine metabolism and the pharmacokinetics of cytarabine in the treatment of
      childhood acute leukemia with high-dose cytarabine].
AB  - OBJECTIVE: It has been reported that high-dose cytarabine (HD-AraC) was very
      effective for childhood hematological malignancies, especially for improving the
      long-term survival of high-risk acute lymphoblastic leukemia (ALL), acute myeloid
      leukemia (AML), and T-cell lymphoid malignancies (T-ALL, T-cell non-Hodgkin's
      lymphoma). This study aimed to evaluate the pharmacokinetics of HD-AraC for
      childhood hematological malignancies, and the relationship between the expression
      of the genes coding the key enzymes for Ara-C metabolism with the outcome of the
      patients. METHODS: The drug levels of Ara-C in plasma and cerebrospinal fluid
      were detected with HPLC while HD-AraC was used, the expression of deoxycytidine
      kinase (dCK) and cytidine deaminase (CDA) mRNA in human leukemia cell lines and
      the bone marrow cells were investigated in 48 cases of childhood hematological
      malignancies with RT-PCR methods, and the relationship between the expression of
      these enzymes mRNA and the outcome of the patients was analyzed. RESULTS: (1)
      When HD-AraC was used, the plasma levels of Ara-C and Ara-U could be respectively
      about 50 times and 25 times higher than those obtained when the patients were
      treated with regular dose of Ara-C treatment, and the level of Ara-C in
      cerebrospinal fluid could reach about 10% of plasma level of Ara-C. (2) There
      were significantly different expressions of dCK mRNA in different childhood acute
      leukemia (AL) patients, which were markedly related to the chemotherapy results.
      The expression of dCK in ALL was much higher than that in AML and relapsed AL
      cases. There were no significant differences in expressions of dCK in T-ALL and B
      lineage ALL. (3) In vitro study found that the expressions of dCK and CDA mRNA
      did not change in leukemia cell lines incubated at different doses and times of
      Ara-C. CONCLUSIONS: HD-AraC was a very effective protocol for childhood
      hematological malignancies for it could significantly elevate the plasma and
      cerebrospinal fluid drug levels. The expression of dCK may be an important factor
      in predicting the long-term outcomes of children with hematological malignancies.
      Good long-term outcomes of the childhood T-ALL could be achieved as the B lineage
      ALL had been treated with HD-AraC regimen. As the expression levels of dCK were
      much lower, it may be necessary for the treatment of AML with HD-AraC for
      consecutive three days.

PMID- 19099731
TI  - [Diagnosis, treatment and gene mutation analysis of the first case with
      dihydropteridine reductase deficiency in the mainland of China].
AB  - OBJECTIVE: The 6-pyruvoyl-tetrahydropterin synthase (PTPS) deficiency is the most
      common type of tetrahydrobiopterin (BH4) deficiency. The reported patients with
      BH4 deficiency are all PTPS deficient found in the mainland of China previously.
      The activity of dihydropteridine reductase in BH4 metabolism has been determined
      for 902 patients with hyperphenylalaninemia in the authors' laboratory since
      2003. The purposes of this study were to characterize the first case with DHPR
      deficiency who was diagnosed in June, 2007, to investigate the clinical
      manifestation, the differential diagnostic criteria, the effect of treatment as
      well as gene mutation of DHPR deficiency. METHODS: (1) A male patient presented
      with poor hand control, seizure, hypotonia and mental retardation since five
      month after birth. His phenylalanine (Phe) level was 600 micromol/L and he was
      diagnosed as hyperphenylalaninemia at the age of one year and six-month. (2) This
      patient was subjected to combined Phe (100 mg/kg) and BH4 (20 mg/kg) loading
      test, to evaluate the degree of Phe level response to BH4. Urinary neopterin and
      biopterin analysis as well as the determination of DHPR activity in dried blood
      spot were also performed. (3) The blood DNA samples of the patient and his
      parents were collected to amplify the seven exons of QDPR gene using related
      primers, and the amplified products were directly sequenced for mutation
      analysis. (4) The patient was treated with BH4 or with a combined small amount of
      Phe-free special milk, neurotransmitter precursors and folic acid after the
      diagnosis and was followed up for clinical effects of treatment. RESULTS: (1) The
      basic Phe level was 476 micromol/L, then it increased to 1355 micromol/L at 3 h
      after taking Phe and slowly decreased to 610 micromol/L at 24h after taking BH4.
      (2) The basic urinary neopterin and biopterin were 2.92 mmol/mol Cr (normally <
      2.61 mmol/mol Cr) and 7.44 mmol/molCr (normally < 2.67 mmol/mol Cr) respectively,
      and biopterin percentage was 71.79% (normally 42.7% - 75.9%). The patient had
      higher biopterin level. (3) The DHPR activity of this patient was (0.27 - 0.51)
      nmol/(min.5 mm disc) which were 6.11% - 10.6% of normal control, so he was
      diagnosed as DHPR deficiency. (4) The analysis of QDPR gene mutation showed that
      the patient carries missense mutation c.515C > T (P172L) from his father and
      nonsense mutation c.661C > T (R221X) from his mother. The c.515C > T is not
      reported before, we also did not find this mutation in 50 normal children. (5)
      The patient started to be treated with large dosage of BH4 (10 - 20) mg/(kg.d) or
      BH4 combined with small amounts of Phe-free milk, neurotransmitter precursors L
      dopa (3 - 5) mg/(kg.d) plus carbidopa, 5-hydroxytryptophan (3 - 5) mg/(kg.d), and
      folic acid 15 mg/d as well at the age of one year and six-month after the
      diagnosis. The seizure has disappeared, the symptoms such as hypotonia have been
      obviously improved and the Phe level was 60 micromol/L at the six months after
      the treatment in this patient. CONCLUSION: (1) The patient with DHPR deficiency
      has common symptoms of BH4 deficiency (such as fair hair, hypotonia, mental
      retardation), and there is metabolic disturbance of folic acid in DHPR
      deficiency. (2) The higher Phe levels slowly decreased after BH4 loading test,
      the urinary biopterin level was very high and the DHPR activity was very low in
      the patient with DHPR deficiency. (3) The c.515C > T may be a new mutation of
      QDPR gene. (4) The DHPR deficient patient must be treated with higher dose of BH4
      (8 - 20) mg/(kg.d), neurotransmitter precursors and folic acid as well.

PMID- 19099732
TI  - [Effects of dexamethasone on lung morphogenesis in rats and the expression of Wnt
      signal transduction pathway in the lung of offspring].
AB  - OBJECTIVE: Multiple signal transduction pathways, for example, Wnt signal
      transduction pathway, fibroblast growth factor (FGF), bone morphogenetic protein
      (BMP) etc, are involved in rat fetal lung development. Wnt signal has been shown
      to play important roles in regulating cell differentiation and proliferation. It
      is demonstrated that antenatal dexamethasone (DEX) use can induce lung dysplasia.
      A rat premature delivery model was developed in this study to compare the effects
      of DEX on antenatal rat fetal lung morphogenesis and the expressions of Wnt7b,
      beta-catenin and glycogen synthase kinase 3beta (GSK-3beta) genes in the lung of
      offspring on 19th day of embryo. METHODS: Twelve pregnant rats were divided into
      three groups randomly: small dose DEX group, large dose DEX group and control
      group with 4 rats in each group. The rats in the control group were injected with
      saline 0.5 ml/d; those in small dose DEX group were injected with DEX 0.4
      mg/(kg.d), the rats in large dose DEX group were injected with DEX 0.8 mg/(kg.d),
      DEX was diluted to 0.5 ml by saline. On the 19th day of gestation, the fetuses
      were surgically taken out and the histologic structures of fetal rat lungs were
      observed with light microscope. The RT-PCR and Western-blot methods were used to
      detect the expressions of Wnt7b, GSK-3beta and beta-catenin genes mRNA and
      protein. RESULTS: (1) Changes of histologic structure included alveolar numbers:
      small dose DEX group (15.6 +/- 2.1), large dose DEX group (13.2 +/- 1.6), control
      group (20.8 +/- 2.0); thickness of alveolar septum: small dose DEX group (11 +/-
      5) microm, large dose DEX group (11 +/- 4) microm, control group (13 +/- 7)
      microm; alveolar space: small dose DEX group (2483 +/- 1336) microm2, large dose
      DEX group (2924 +/- 1705) microm(2), and control group (1913 +/- 764) microm(2).
      All the parameters showed significant difference between DEX groups and control
      group. (P < 0.01 for all comparisons). (2) The expressions of Wnt7b (0.55 +/-
      0.19, 0.64 +/- 0.54) and beta-catenin (2.03 +/- 0.58, 2.40 +/- 0.89) genes mRNA
      of the study groups were significantly higher as compared with those of the
      control group [Wnt7b (0.18 +/- 0.10), beta-catenin (1.77 +/- 0.54)] (P < 0. 05
      for all comparisons) while the expressions of GSK-3beta (1.0 +/- 0.5) were lower
      than those of the control group (1.1 +/- 0.6) (P < 0. 05). The expressions of GSK
      3beta protein in cytoplasm of the study groups [(26.6 +/- 19.7) microg, (10.7 +/-
      7.4)microg] reduced gradually while beta-catenin's [(79.5 +/- 1.2) microg, (148.3
      +/- 30.4) microg] in the nucleus enhanced simultaneously compared with the
      control group [(50.0 +/- 00.0) microg ]. CONCLUSIONS: Small dose of antenatal DEX
      usage can improve the fetal lung development, larger dose of DEX may have
      negative effect on rat fetal lung morphogenesis. Antenatal DEX usage can change
      the expressions of Wnt7b, GSK-3beta and beta-catenin genes mRNA and protein,
      these changes may result in paramorphia during pregnancy.

PMID- 19099733
TI  - [Diagnostic values of serum orexin-A levels in children with obstructive sleep
      apnea-hypopnea syndrome].
AB  - OBJECTIVE: Currently people regard polysomnography (PSG) monitoring as the golden
      standard for diagnosis of obstructive sleep apnea-hypopnea syndrome (OSAHS) in
      children. However, due to the high cost, time and manpower consuming, PSG is not
      applicable to epidemiological investigation and clinical screening, especially
      not suitable for child patients and remote hospitals in Xinjiang. Therefore, it
      is of important clinical significance to find out a simple method (e.g. a kind of
      serum index) to primarily screen out suspicious patients for early diagnosis and
      treatment. The present study was conducted to assess the clinical usefulness of
      the measurement of orexin-A concentration in serum as a diagnostic predictor to
      screen patients with OSAHS in children. METHODS: Serum orexin-A concentration was
      measured with enzyme immunoassay (EIA) kit in 60 patient with snoring before
      performing polysomnography (PSG). Subsequently all the subjects underwent PSG
      test. Forty subjects were diagnosed as having OSAHS, and twenty subjects had no
      OSAHS. These 20 non-OSAHS subjects served as controls. Compared with the PSG
      results the clinical usefulness of the measurement of orexin-A concentration in
      serum was assessed as a diagnostic predictor to screen patients with OSAHS.
      Correlation between orexin-A levels and apnea hypoventilation index (AHI), micro
      arousal index (MAI) and lowest SaO2 (LSaO2) were analyzed. RESULTS: The serum
      orexin-A levels in the OSAHS group [(0.49 +/- 0.10) microg/L] was significantly
      higher than that of the control group [(0.28 +/- 0.11) microg/L, P < 0.01]. If a
      patient's level of orexin-A was higher than 0.36 microg/L, the patient more
      likely to have OSAHS. The sensitivity rate was 85.0% and the specificity was
      80.0%. Serum orexin-A levels in children with OSAHS correlated positively with
      the AHI (r = 0.427, P < 0.05) and MAI (r = 0.468, P < 0.05), but correlated
      negatively with the LSaO2 (r = -0.527, P < 0.01) and the mean oxygen saturation
      (MSaO2) (r = -0.541, P < 0.01), not correlated significantly with the BMI (r = 
      0.212, P > 0.05). The serum orexin-A levels in the OSAHS children after who under
      went tonsillectomy and adenoidectomy significantly decreased (P < 0.05) 3 months
      after surgery as compared with pre-operation level. CONCLUSION: These findings
      suggest that the serum level of orexin-A could be used as a predictor in
      screening for OSAHS children and a biological marker of the severity of OSAHS
      children.

PMID- 19099734
TI  - [Blood glucose profile in children and adolescents in Beijing area].
AB  - OBJECTIVE: There are scant data about normal reference values of blood glucose
      (BG) in children. This study was conducted to learn the BG profile of children
      and adolescents in Beijing area. METHOD: The population for survey was selected
      as a stratified cluster sample from 8 urban and 10 rural areas in Beijing.
      Fasting capillary blood glucose (FCBG) was determined in 19,593 children and
      adolescents aged 6 to 18 years in 4 urban and 3 rural areas using
      haemosaccharometer model II [Roche Diagnostic, (Shanghai) Ltd]. RESULTS: There
      were 1 9112 (97.5%) individuals with complete records, the mean age was 12.1 +/-
      3.3 years (ranged from 6 to 18.9 years); 9514 (49.8%) were boys, 9598 (50.2%)
      were girls, 9792 were (51.2%) from urban areas and 9320 (48.8%) from rural areas.
      The average level of FCBG in boys was higher than that in girls (4.7 +/- 0.5 vs.
      4.5 +/- 0.5, u = 28.0, P < 0.01). Among urban children, the trend of variation of
      FCBG was similar between boys and girls, the levels of FCBG increased with age,
      the peak of FCBG was reached at 12-13 years in urban girls, and from the age of
      15 years, the level of FCBG declined. In boys, the FCBG level increased slowly
      from 13 years of age, there was no significant variation until 17 years old, and
      declined at the age of 18. Among suburban children, the trend of variation of
      FCBG was similar between boys and girls, both of them had two peaks, from 6 to 11
      years old, FCBG of both boys and girls increased with age, and both reached the
      first peak at the age of 11 years. While at 13 years of age, there was an obvious
      drop in FCBG level. From 14 years of age on, there was a rise of FCBG in both
      boys and girls, and the second peak of FCBG was reached at 15 and 16 years of age
      in girls and boys respectively. The FCBG level of urban children was higher than
      that of rural children (4.7 +/- 0.5 vs. 4.6 +/- 0.5, u = 13.8, P < 0.01). The
      level of FCBG in overweight and obese children was higher than that of normal
      children. More boys, more obese and more urban children had abnormal FCBG.
      CONCLUSIONS: The blood glucose level of children was associated with age, gender,
      obesity and district.

PMID- 19099735
TI  - [Diagnosis of Alport syndrome by immunohistochemical staining of type IV collagen
      alpha chains in paraffin-embedded renal sections].

PMID- 19099736
TI  - [Expression of foxp3 and glucocorticoid induced tumor necrosis factor receptor
      mRNA of T regulatory cell in food allergy animal models].

PMID- 19099737
TI  - [Effects of bovine colostrum insulin-like growth factor-1 on the blood lipid, the
      lipid metabolic enzyme, and apolipoproteins of the rats with nephrotic syndrome].

PMID- 19099738
TI  - [Airway hyperresponsiveness in patients with allergic rhinitis].

PMID- 19099739
TI  - [Two cases of exercise-induced acute renal failure].

PMID- 19099740
TI  - [Clinical characteristics of septicemia caused by Pseudomonas aeruginosa in
      children].

PMID- 19099741
TI  - [Dipylidium caninum infection in a child].

PMID- 19099742
TI  - [Infantile Pseudomonas aeruginosa septicemia: a case report].

PMID- 19099743
TI  - [Update on the prevention of allergic disease in childhood].

PMID- 19099744
TI  - [Fetal heart failure].

PMID- 19099745
TI  - [Status quo and pondering of clinical research in China].

PMID- 19099746
TI  - [For the health and well-being of children--an overview of the 25th World
      Congress of Pediatrics].

PMID- 19099747
TI  - [Adrenal function evaluation using ACTH stimulation test in children with sepsis
      and septic shock].
AB  - OBJECTIVE: Sepsis and septic shock remain a common problem that results in
      significant mortality and morbidity in pediatric intensive care units (PICU).
      According to literature, the use of more physiologic steroid replacement therapy
      is associated with hemodynamic and survival benefits in adult patients with
      relative adrenal insufficiency (RAI) and catecholamine-resistant septic shock.
      But little information is available in children. The aim of the current
      prospective study was to determine the prevalence of adrenal insufficiency in
      children with sepsis and septic shock using a low-dose adrenocorticotropic
      hormone (ACTH) stimulation test (1 microg/1.73 m2) in children. METHODS: The
      authors performed cortisol estimation at baseline and after low-dose (1
      microg/1.73 m2) ACTH stimulation at 30 mins in children during the first 24 hours
      in patients with sepsis or septic shock admitted to our PICU. Adrenal
      insufficiency was defined as a response < or = 90 microg/L. Absolute adrenal
      insufficiency (AAI) was further defined as baseline cortisol (T0) < 200 microg/L
      and RAI insufficiency by T0 > or = 200 microg/L. RESULTS: Sixty-two consecutive
      cases with sepsis and septic shock admitted to PICU of Shanghai Jiaotong
      University Affiliated Children's Hospital from April, 2006 to March, 2007. The
      median age was 37.6 months (range, 2 - 168 months), and their gender distribution
      was 42 (67.7%) males and 20 (32.3%) females, 53 cases had sepsis (85.5%) and 9
      had septic shock (14.5%). The mean pediatric critical illness score (PCIS) was
      79.3 +/- 9.2 and median pediatric risk of mortality score (PRMSIII) 11.3 (5 -
      19), respectively. Overall mortality of sepsis and septic shock was 27.42%. The
      evaluation of adrenal insufficiency was conducted as follows. (1) The mean
      cortisol levels at baseline (T0) and 30 mins after ACTH stimulation (T1) were
      (318.6 +/- 230.4) microg/L, (452.3 +/- 230.7) microg/L and (454.7 +/- 212.7)
      microg/L, (579.3 +/- 231.9) microg/L in patients with severe sepsis and septic
      shock group, respectively. There were no significant difference between the two
      groups (P > 0.05). (2) The proportion of patients with adrenal insufficiency in
      the study population was 40.3% as defined by a response < or = 90 microg/L post
      test. The proportion of patients with adrenal insufficiency in sepsis and septic
      shock were 39.6% and 44.4%, respectively (chi2) = 0.073, P > 0.05). (3) The serum
      T0 and T1 levels were (320.5 +/- 223.9) microg/L, (462.3 +/- 212.0) microg/L and
      (384.3 +/- 258.3) microg/L, (500.7 +/- 470.6) microg/L, respectively, and the
      proportion of patients with adrenal insufficiency were 37.8% and 47.1% in the
      survivors and the dead (P > 0.05). The levels of T0 and T1 were related to the
      PCIS (P < 0.05). The morbidity of adrenal insufficiency was not related to the
      PCIS, PRISMIII, and number of organ that developed functional insufficiency (P >
      0.05). CONCLUSIONS: Adrenal insufficiency may occur in patients with sepsis and
      septic shock in children. ACTH stimulation test may be helpful to determine
      whether corticosteroid therapy has a survival benefit in patients with relative
      adrenal insufficiency. A low-dose ACTH stimulation test can be used to evaluate
      the adrenal function status of severe sepsis and septic shock in children.

PMID- 19099748
TI  - [Clinical analysis of community-acquired Pseudomonas aeruginosa septic shock].
AB  - OBJECTIVE: This study sought to analyze the clinical manifestations and
      intervention of fulminant septic shock in community-acquired Pseudomonas
      aeruginosa septicemia. METHODS: We retrospectively reviewed the medical records
      for diagnosis, antibiotic therapy, clinical course of septic shock, respiratory
      support, laboratory data etc. RESULTS: Eight of nine cases with P. aeruginosa
      septic shock died. Fever (nine cases) and cough (three cases) or diarrhea (3
      cases) were the 2 most common initial symptoms, three cases developed skin
      gangrenosum later. Pseudomonas aeruginosa infection was not considered in any of
      the cases before death or blood culture showed positive result. Only 3 cases were
      initially treated with susceptible antibiotic regimen but no anti pseudomonas
      combination therapy was applied, susceptible antibiotic monotherapy was applied
      in 7 cases after transfer to the ICU. The mean latency of shock occurrence was
      5.1 hours (range 0 to 21 hours) after admission, the mean duration from the
      occurrence of shock to death was 13.8 hours (range, 1 - 32 hours). All the
      patients were transfer red to ICU for shock, the appropriate resuscitation of
      shock patients was delayed by 49.3 minutes (range 25 - 80 minutes) by transfer.
      Only two cases were diagnosed and treated for shock on admission; after
      transferred to ICU, only 5 patients were diagnosed as having shock, and only 3
      received anti-shock treatment. Eight of the patients died of persistent shock. In
      6 patients who died, mechanical ventilation was not applied until cardiac arrest
      occurred. All the patients had hypoalbuminaemia, elevated serum C-reactive
      protein concentration, leukopenia and 6 cases had DIC. CONCLUSION: The initial
      presentation of the cases with community-acquired Pseudomonas aeruginosa
      septicemia was nonspecific with fever and cough or diarrhea. Clinicians often
      underestimated the severity of the infection, few patients received effective
      antimicrobial therapy. The authors suggest that an anti-pseudomonas antibiotic
      should be included in the initial empiric antibiotic regimen to cover P.
      aeruginosa high-risk patients; the front-line clinician should be educated for
      early recognition and aggressive resuscitation of P infection. aeruginosa
      septicemia.

PMID- 19099749
TI  - [Effect of continuous veno-venous hemodiafiltration on hemodynamics of piglets
      with endotoxin-induced acute lung injury].
AB  - OBJECTIVE: To investigate the effect of continuous veno-venous hemodiafiltration
      (CVVHDF) on endotoxin-induced acute lung injury (ALI) of piglets. METHODS:
      Eighteen piglets were randomly divided into three groups: control group (n = 6);
      heparin group (n = 6) and CVVHDF treatment group (n = 6). All the animals were
      anesthetized by muscle injection of ketamine (30 mg/kg), then placed in supine
      position, received continuous intravenous infusion of ketamine with the rate of
      10 mg/(kgxh). After placing a 4.5 cm (inner diameter) tracheal tube via
      tracheostoma, controlled mechanical ventilation was established using the
      assisted-controlled ventilation option of the NEWPORT 200. Respiratory rate at 30
      breath/min; PIP at 10 cm H2O (1 cm H2O = 0.098 kPa); PEEP at 2 cm H2O and
      fraction of inspired oxygen at 0.3. A vein catheter was placed into right vena
      jugularis interna to administer a Ringer's solution. Initially, at a rate of 10
      ml/kg, followed by a rate of 15 ml/kg when the mean arterial blood pressure was
      below 70 mm Hg (1 mm Hg = 0.133 kPa), the rate of 20 ml/kg was used when the mean
      arterial blood pressure was below 60 mm Hg. An 8Fr double-lumen catheter was
      inserted into left femoral vein and served as the pathway for CVVHDF. A
      Pulsiocath Pcco catheter was positioned into left femoral artery to monitor the
      circulatory parameters. All catheters were flushed with heparinized saline to
      prevent clotting. Then all the animals were given intravenous infusion of 150
      microg/kg endotoxin within 30 minutes to induce ALI. When the oxygenation index <
      300 and pulmonary compliance < 30% of the baseline, the animals of heparin group
      received heparin infusion to maintain blood active coagulation time (ACT) 180 -
      250 s, the animals of treatment group received CVVHDF with the blood flow of 50
      ml/min, replacement rate of 300 ml/h, dialysis rate of 600 ml/h and the
      ultrafiltrate rate of 350 ml/h for six hours, heparin infusion to keep blood ACT
      180 - 250 s. The circulatory parameters: heart rate (HR), mean arterial blood
      pressure (MABP), central venous pressure (CVP), pulse contour cardiac output
      index (PCCI); systemic venous resistance index (SVRI), cardiac function index
      (CFI), external venous lung water index (EVLWI), left ventricular contractile
      index (dPmx); respiratory parameters: respiratory rate (RR), pulmonary compliance
      (Cdyn) were monitored; arterial blood gas analysis was performed and oxygenation
      index (PaO2/FiO2) was calculated. All the parameters were recorded at baseline
      (B), onset of ALI (A 0 h), two hours (A 2 h), four hours (A 4 h), six hours (A 6
      h) after ALI. RESULTS: No significant difference in circulatory parameters,
      respiratory parameters and blood gas analysis were found at B and A 0 h among the
      three groups. When the ALI occurred, PaO2/FiO2, Cdyn, MABP and PCCI of the three
      groups decreased; HR, RR, EVLWI, SVRI increased. After four hours of ALI, the RR,
      EVLWI, SVRI, CFI and dPmx of treatment group were improved, the differences were
      significant compared with the other two groups (P < 0.05). After six hours of
      ALI, the HR, PCCI, MABP, PaO2/FiO2 and Cdyn of treatment group were significantly
      improved, compared with control group and heparin group (P < 0.05). There were no
      significant differences in any of the parameters between control group and
      heparin group. The difference in CVP among three groups was not significant.
      CONCLUSION: CVVHDF has a good effect on hemodynamics of the endotoxin-induced ALI
      of the piglets.

PMID- 19099750
TI  - [Clinicopathological analysis of 141 pediatric autopsy cases].
AB  - OBJECTIVE: To summarize the major pathological findings, causes of deaths and
      reasons for misdiagnosis of 141 autopsy cases and thereby to improve the
      diagnosis level and reduce misdiagnosis. METHOD: A retrospective analysis of
      pathological reports and clinical materials of 141 pediatric autopsy cases from
      June, 1986 to June, 2006 of our department was performed. Classification was
      based on (1) international classification of diseases of the World Health
      Organization; (2) age: cases 28 d-3 years old were defined as infants and young
      children group, -7 yeas olds were defined as preschool age group, -14 years olds
      were school age group; (3) when statistics was conducted, the first 3 items of
      the clinical diagnoses were counted. If one of them was consistent with the
      pathological diagnosis, it was regarded as basically in accordance with the
      pathology, if none of the first 3 was consistent with pathological diagnosis, the
      case was regarded as misdiagnosed. RESULTS: (1) The top three major pathological
      diagnosis and causes of death were: 1) Classified according to system: 41 cases
      had tumor (29.1%), 25 cases had respiratory diseases (17.7%), 18 cases had
      infectious diseases (12.7%); 2) Classified according to disease: 18 cases had
      malignant histiocytosis, 12 cases had sepsis, 11 cases had lobular pneumonia. (2)
      The causes of deaths changed gradually. The top cause of death was respiratory
      diseases during the former 10 years and was tumor during the latter 10 years; the
      materials showed that 95 cases were 28 d-3 years old (67.4%), and some rare
      diseases, such as mediastinal and lung chorionic epithelioma (choriocarcinoma),
      and pulmonary alveolar proteinosis were found. (3) In 90 cases the clinical
      diagnosis was basically in accordance with the pathological diagnosis (63.8%) and
      misdiagnosis was found in 51 cases (36.2%). CONCLUSION: For clinical diagnosis of
      critically ill patients, both common and rare diseases should be considered.
      Analysis of autopsy materials could confirm and/or correct clinical diagnosis and
      is helpful to summarize clinical diagnosis experience.

PMID- 19099751
TI  - [Retinoic acid diminished the expression of lung tissue matrix metalloproteinase
      2 and matrix metalloproteinase-9 in hyperoxia-exposed premature rats through
      regulating mitogen-activated protein kinases].
AB  - OBJECTIVE: To further investigate the protective effect of retinoic acid (RA) on
      hyperoxia induced lung injury and the role of RA as a modulator on mitogen
      activated protein kinases (MAPKs). METHODS: Establishment of hyperoxia (85%)
      induced lung injury model of premature Sprague-Dawley (SD) rats: 21 d gestational
      age SD rat's fetuses (term = 22 d) were delivered by hysterectomy. Within 12 - 24
      h after birth, the premature rat pups were randomly divided into 4 groups: Group
      I, air-exposed control group; Group II, hyperoxia-exposed group; Group III, air
      plus RA-exposed group, Group IV, hyperoxia plus RA-exposed group. Group I and III
      were remained in room air, and group II and IV were placed in 85% oxygen. The
      pups in Group III and IV were injected with RA (500 microg/kg, every day)
      intraperitoneally. The entire lung tissues of premature rat pups were collected
      at 4 d, 7 d and 14 d. The mRNA levels of MMP-2 and MMP-9 were detected by semi
      quantitative reverse transcription polymerase chain reaction (RT-PCR). MMP-2 and
      MMP-9 activities were measured by zymography. Western blot was used to detect
      phosphorylated and total nonphosphorylated form of ERKs, JNKs and p38. RESULTS:
      Exposure to oxygen for 4 d, 7 d, and 14 d resulted in increased mRNA levels of
      MMP-2 and MMP-9 compared with air-exposed control group (P < 0.01 for all). The
      mean protein levels of active MMP-2 and pro/active MMP-9 after exposure to O2
      were higher than air control groups on each experimental day (P < 0.01 or <
      0.05). The phosphorylated ERK1/2, JNK1/2 and p38 proteins in hyperoxia-exposed
      group increased markedly compared with air-exposed control group (P < 0.01 for
      all). The pups treated with RA in the hyperoxic environment expressed
      significantly lower mRNA levels of MMP-2 and MMP-9 than the hyperoxic control
      pups on each experimental day (P < 0.05 for all). The levels of active MMP-2 and
      pro/active MMP-9 decreased to a different degree after RA treatment in hyperoxia
      exposure rat pups. In addition, RA treatment led to a decrease of p-JNK1/2 and p
      38 (P < 0.01 for all) protein levels and a further elevation of p-ERK1/2 compared
      with hyperoxia-exposed group. CONCLUSION: Hyperoxia exposure elevated the
      expression of MMP-2 and MMP-9 markedly, which played a role in oxygen-induced
      lung injury. RA could have a protective effect on hyperoxia induced lung injury
      by decreasing active levels of JNK and p38, which subsequently reduce the
      expression and activation of MMP-2 and MMP-9.

PMID- 19099752
TI  - [Values of diffusion-weighted magnetic resonance imaging in the early detection
      of periventricular leukomalacia in preterm infants].
AB  - OBJECTIVE: Periventricular leukomalacia (PVL), the principal form of brain injury
      in the premature infant, is characterized by overt focal necrotic lesions in
      periventricular white matter and diffuse cerebral white matter injury. The early
      detection of the disease is not consistently possible with cranial
      ultrasonography or conventional magnetic resonance imaging (MRI). Recently,
      diffusion-weighted imaging (DWI) has been shown to be highly sensitive in
      detecting acute ischemic cerebral injury. This study aimed to evaluate possible
      role of DWI in early diagnosis of PVL. METHODS: Images and clinical data from 12
      preterm infants with PVL diagnosed in our NICU from August, 2005 to April, 2007
      were reviewed. MRI using conventional and diffusion-weighted imaging, as well as
      the assays of blood routine test, serum bilirubin, C-reactive protein (CRP),
      blood culture, blood gas analysis, blood sugar and serum ions were performed in
      these preterm infants. All examinations were performed on a 3.0-T MRI system
      (Philips Intera Acheva Magnetom Vision) with echo-planar imaging capability with
      the use of a standard protocol. The imaging protocol for all the patients
      contained diffuse weighted images (EPI-SE, TR = 2144 ms, TE = 56 ms), T1-weighted
      images (TR = 389 ms; TE = 15 ms; slice thickness = 4 mm) as well as T2-weighted
      images (TR = 3035 ms; TE = 100 ms; slice thickness = 4 mm). The first MR
      examinations were performed in all these twelve preterm infants (mean age 4.5
      days, range 2 - 7 days). Conventional MRI and DWI sequences obtained in the acute
      phase were compared. All the neonates underwent another two MRI examinations up
      to 2 and 4 weeks after delivery; five subjects also underwent MRI follow-up for
      up to 4 - 8 months (in 3 for 4 months, in 1 for 7 months, and in another for 8
      months). Qualitative evaluations were performed to assess the presence of DWI
      changes compatible with PVL. RESULTS: The gestational ages of these twelve
      patients were from 31 to 35 weeks. None of them had intrauterine distress or
      birth asphyxia. None of the patients had localized neurological signs in the
      early course except for abnormal muscular tone of some extent, but seizure and
      apnea were their major symptoms. No other positive signs of nervous system was
      found in these preterm infants with PVL. First DWI detection (on the average of
      4.5 days) in all these infants showed bilateral, symmetric, diffuse high signal
      intensity (including genu and plenum of corpus callosum), while conventional MRI
      showed normal images on both T1- and T2-weighted imaging; two weeks later, DWI
      showed irregularly high, low mixed signals while conventional MRI showed punctate
      high signal intensity on T1-weighted imaging and slightly lower signal on T2
      weighted imaging. Four weeks later, DWI showed cystic low signal intensity where
      conventional MRI showed low signal intensity on T1-weighted imaging and high
      signal intensity on T2-weighted imaging (cystic PVL). Four months later, DWI
      showed that the cystic cava became diminished and disappeared, while conventional
      MRI showed reduced cerebral white matter and dilation of ventricle. CONCLUSION:
      Bilateral, symmetric, diffuse high signal intensity on DWI seems to be the
      earliest evidence of PVL; diffusion-weighted imaging performed in the acute phase
      of the disease may have a higher correlation with later evidence of PVL than does
      conventional MR imaging. DWI is likely to be a considerable technique in the
      early assessment of white matter injury and later PVL in preterm infants.

PMID- 19099753
TI  - [Expression of connective tissue growth factor and its down-regulation by
      simvastatin administration in pulmonary hypertensive rats].
AB  - OBJECTIVE: To explore the role of expression of connective tissue growth factor
      (CTGF) in pulmonary vascular remodeling of pulmonary hypertensive rats, and
      investigate the regulation of CTGF expression by simvastatin in this animal
      model. METHODS: Eighty male Sprague-Dawley rats (350 to 400 g) were randomized to
      7 groups. The rats in group PM(1 - 21) (n = 10) and PM(1 - 35) (n = 12) were
      treated with pneumonectomy + monocrotaline (MCT), and sacrificed at the 21st or
      35th experimental day;those in groups PMS(1 - 35) (n = 12), PMS(21 - 35) (n =
      12), PMV(1 - 35) (n = 12) and PMV(21 - 35) (n = 12) were given daily lavage of
      simvastatin (or vehicle) as intervention measure which began from the 1st and
      21st experimental days, respectively; additional 10 rats were used as control
      without any intervention. The animals were sacrificed at the end of experiment
      (35 th day) as hemodynamic measurements and study on the morphological parameters
      relevant to pulmonary vascular remodeling were performed on each group of rats.
      The expression of ET-1 mRNA, CTGF mRNA and protein, and synthesis of collagen in
      these pneumonectomized, MCT-treated rats were compared between control and rats
      treated with simvastatin. RESULTS: Rats in PM(1 - 35) Group developed severe PAH
      (mPAP = 39.75 +/- 3.62 mm Hg) (1 mm Hg = 0.133 kPa), right ventricular
      hypertrophy [RV/(LV + S) ratio = 0.627 +/- 0.040], and arterial medial
      hypertrophy (WT% = 61.73 +/- 5.39), these parameters of the control animals were
      17.10 +/- 1.20 mm Hg, 0.262 +/- 0.018 and 14.71 +/- 1.16, respectively. CTGF mRNA
      and protein were mainly located in pulmonary arterial smooth muscle cells and
      interstitial macrophage shown by in situ hybridization and immunohistochemistry,
      respectively. The expression of ET-1 mRNA and CTGF mRNA detected by fluorescent
      quantitative RT-PCR in Group PM(1 - 35) were significantly increased in
      comparison with controls, and so did the CTGF protein expression determined by
      Western blotting in these diseased rats. The content of hydroxyproline (1.30 +/-
      0.19 microg/mg wet lung) was remarkably higher than that of control animals (0.56
      +/- 0.10 microg/mg wet lung). The up-regulation of ET-1 and CTGF gene expression,
      and elevated synthesis of hydroxyproline were reversed in rats intervened with
      simvastatin. The pulmonary hypertension, right ventricular hypertrophy and medial
      hypertrophy were attenuated in all simvastatin-treated rats no matter the
      intervention was initiated from the beginning or midway of the study. CONCLUSION:
      The up-regulation of CTGF gene expression may play an important role in the
      development of pulmonary vascular remodeling in PAH. Simvastatin can prevent and,
      to some extent, reverse the vascular remodeling via down-regulation of CTGF gene
      expression.

PMID- 19099754
TI  - [Nasal immune tolerance to passively transferred myasthenia gravis in young
      mice].
AB  - OBJECTIVE: Young C57BL/6 (B6) mice were treated with a specific tolerogen-dual
      analogue (Lys262-Ala207) intranasally to observe its effect on the invasion
      process of mice model and the clinical symptoms, to assess its clinical effects,
      and to explore the underlying mechanisms and feasibility of nasal mucosal
      tolerance explored. METHODS: Passively transferred myasthenia gravis (PTMG) was
      induced by mAb35 on B6 young female mice. Sixty mice were divided equally into
      three groups: tolerance group, model group and control group. Lys262-Ala207 was
      given intranasally (250 microg/mouse) to tolerance group with mAb35 for 10
      successive days before immunization. Model group received PBS 50 microl only. The
      body weight and clinical scores were evaluated. The serum levels of AChRAb and
      the main cytokines (IL-4, IFN-gamma, TGF-beta1) were detected with ELISA.
      RESULTS: The model group had typical myasthenia symptoms. B6 mice of tolerance
      group had less severe symptoms compared with control groups. The clinical
      symptoms of tolerance group were relieved. The level of AChRAb in tolerance group
      [(16.01 +/- 1.09) mg/L] was significantly lower than that of model group [(28.12
      +/- 1.28) mg/L] (t = 44.37, P < 0.01). IL-4 and IFN-gamma levels in tolerance
      group [(141.02 +/- 3.11) ng/L, (187.99 +/- 4.67) ng/L] were significantly lower
      than those of model group [(193.37 +/- 3.95) ng/L, (320.46 +/- 2.14) ng/L] (t =
      37.20, 51.69, P < 0.01). The level of TGF-beta1 in tolerance group [(437.19 +/-
      1.93) ng/L] was higher than that of model group [(175.63 +/- 3.12) ng/L] (t =
      36.07, P < 0.01). But there were still significant change as compared to those in
      control group (t = 26.65, 31.05, 49.02, P < 0.01). CONCLUSIONS: Nasal
      administration of Lys262-Ala207 ameliorated muscular weakness in PTMG young mice.
      The therapeutic effect is possibly correlated with the function of immune system.

PMID- 19099755
TI  - [Unilateral spatial neglect in children with attention deficit hyperactivity
      disorder].
AB  - OBJECTIVE: To detect unilateral spatial neglect phenomenon in children with
      attention deficit hyperactivity disorder (ADHD) and to test the hypothesis that
      the phenomenon is associated with ADHD. METHODS: Thirty two boys met with ADHD
      diagnostic criteria of DSM-IV(TM) (ADHD group) and the 32 healthy boys without
      ADHD as control group participated in this study. All the participants received
      the flowing managements. The spatially sensitive tools of the Line Bisection test
      and the Star Cancellation test and some general measures (non-spatial) were used
      to evaluate spatial attention. RESULTS: (1) The score of Line Bisection test of
      boys with ADHD was (-9.37 +/- 6.57), and that of the control group was (-5.46 +/-
      4.69), the difference between two groups was significant (t = -2.735, P < 0.01);
      the difference in left side score of the Star Cancellation test was statistically
      significant (t = -3.78, P < 0.01) in the ADHD group versus the control group
      (11.44 +/- 5.55 vs. 16.34 +/- 4.82), and the left side score was also lower than
      the right side one (17.13 +/- 6.36), the difference was significant (t = -3.09, P
      < 0.01). (2) Both groups' scores of the Line Bisection test were biased to the
      right side of "0" value respectively (ADHD group: t = -8.064, P < 0.01; control
      group: t = -6.585, P < 0.01), each side of which was lower versus "expected
      value" "27/27" on right side (ADHD group: t = -8.78, P < 0.01; control group: t =
      -7.39, P < 0.01) and left side (ADHD group: t = 15.85, P < 0.01; control group: t
      = -12.52, P < 0.01). CONCLUSIONS: The results suggest that left spatial neglect
      may be a common general phenomenon of school age boys. Compared with normal
      children, children with ADHD may have obvious left spatial neglect, which suggest
      that there be a common neurophysiologic mechanism between left spatial bias and
      ADHD.

PMID- 19099756
TI  - [Summary of the third national conference of pediatric sleep medicine
      collaborative group].

PMID- 19099757
TI  - [Ambulatory blood pressure monitoring in pediatric patients with kidney
      diseases].
AB  - OBJECTIVE: From the end of 1990s, ambulatory blood pressure monitoring (ABPM),
      which measures ambulatory blood pressure (ABP) during a whole 24 hours, has been
      applied. However, there are few studies on the use of ABPM in children with
      kidney disease, especially those whose renal function is normal or mildly
      impaired in both China and abroad. This study aimed to explore the
      characteristics of ABP in patients with common pediatric kidney diseases.
      METHODS: Totally 33 patients (21 boys and 12 girls) hospitalized in our hospital
      with kidney diseases aged from 5 - 16 yrs from February 2005 to January 2006 were
      enrolled; 28 cases (85%) had normal renal function [Ccr > or = 90 mmol/(Lx1.73
      m2)]. None of them were taking anti-hypertensive drugs during the monitoring.
      Twenty-four-hour ABP monitoring was performed by using Welch Allyn ABPM 6100 in
      the patients. ABPM recordings of 1141 healthy children performed in Germany in
      1997 was used as the normal reference data, which was the largest pediatric study
      and was most commonly used in the world up to now. RESULTS: The incidence of
      nocturnal hypertension was significantly higher than that of diurnal hypertension
      (P < 0.01); nocturnal systolic/diastolic blood pressure load (29.1 +/-
      34.5)%/(24.9 +/- 34.3)% and index (0.95 +/- 0.11)/(0.90 +/- 0.18) were
      significantly higher than diurnal systolic/diastolic blood pressure load (12.9 +/
      23.6%/9.3 +/- 19.1%) and index (0.88 +/- 0.09)/(0.77 +/- 0.12) (P < 0.01);
      nocturnal systolic/diastolic dipping rate (7.3 +/- 5.3)%/(10.5 +/- 10.6)% in the
      patients was significantly lower than that in the healthy children (13 +/-
      6)%/(23 +/- 9)% (P < 0.01); the incidence of non-dipper in 33 patients was 72.7%,
      even with the same incidence in patients with normal blood pressure. Five cases
      had elevated CBP whose ABP were also elevated; while among the 28 cases with
      normal CBP, 6 cases were found to have elevated ABP. CONCLUSIONS: ABPM can detect
      the nocturnal hypertension and abnormal rhythm of blood pressure during 24-hour
      in patients with pediatric nephropathy. ABPM can also disclose masked
      hypertension, thereby warrant to follow-up and start earlier intervention.

PMID- 19099758
TI  - [Mutation of hepatitis B virus S gene in children with hepatitis B virus
      associated glomerulonephritis].
AB  - OBJECTIVE: Hepatitis B virus-associated glomerulonephritis (HBV-GN) is an immune
      complex-mediated glomerulonephritis. The present study was conducted to identify
      HBV S gene mutation in children with HBV-GN. METHODS: Serum HBV DNA was extracted
      in 53 children, including 30 with HBV-GN, 5 with HBV-carrying nephrosis (control
      group 1), and 18 HBV carriers (control group 2). HBV S gene sequence was
      amplified by polymerase chain reaction (PCR). The PCR products were sequenced
      directly and compared with AY167097.1, an epidemic HBV strain in China. RESULTS:
      (1) The adw serotype of HBV was found in all the 30 cases with HBV-GN, 5 cases
      with HBV-carrying nephrosis and 17 HBV carriers except for 1, in whom adr
      serotype was identified. (2) HBV genotype B was found in 29 children with HBV-GN,
      5 cases with HBV-carrying nephrosis and 17 HBV carriers, genotype E was found in
      a child with HBV-GN, and genotype C in an HBV carrier. (3) A total of 17 kinds of
      different single nucleotide change in HBV S gene were identified in 21 of 30
      (70%) HBV-GN patients. Among them, 16 of 21 (76.2%) nucleotide mutations resulted
      in amino acid substitution. It was interesting that most (11/16, 68.8%) amino
      acid substitutions involved threonine, serine and tyrosine, the potential
      phosphorylation sites of mitogen-activated protein kinase (MAPK) and protein
      tyrosine kinase (PTK) in HBV protein. Single nucleotide changes which didn not
      result in amino acid substitution were found in 2 HBV-carrying nephrosis
      patients, 2 HBV carriers and 5 cases with HBV-GN. CONCLUSION: Single nucleotide
      changes in HBV S gene were found in most children with HBV-GN. Most mutations in
      HBsAg resulted in amino acid substitutions involving threonine, serine and
      tyrosine, which may play a role in the pathogenesis of HBV-GN.

PMID- 19099759
TI  - [Retrospective analysis of clinical features of Kawasaki disease in 138 children
      below 6 months of age].

PMID- 19099760
TI  - [Application of hydrogen proton magnetic resonance spectrum in hypoxic-ischemic
      encephalopathy in full-term neonates].

PMID- 19099761
TI  - [Effect of ethanol on cardiac looping of zebrafish embryos].

PMID- 19099762
TI  - [Protocol for diagnosis and treatment of childhood malignant germ cell tumor].

PMID- 19099763
TI  - [Clinical study and prognosis of pediatric renal transplantation].

PMID- 19099764
TI  - [In vitro generation of hematopoietic stem cells from embryonic stem cell to
      reconstruct hematopoiesis].

PMID- 19099765
TI  - [Deliberating with the authors of the article entitled "Suppurative
      meningoencephalitis complicated with intrinsic endophthalmitis in a newborn
      infant"].

PMID- 19099767
TI  - [Report of a case with idiopathic infantile arterial calcification].

PMID- 19099768
TI  - [Report of a case with post-transplant lymphoproliferative disorder].

PMID- 19099769
TI  - [A case with childhood lymphomatoid papulosis].

PMID- 19099771
TI  - [Implantation of cardioverter-defibrillator in treatment of congenital long QT
      syndrome in a child].

PMID- 19099770
TI  - [Childhood intra-abdomen inflammatory myofibroblastic tumors in two cases].

PMID- 19099772
TI  - [Pay much attention to severe enterovirus 71 infection in children].

PMID- 19099773
TI  - [Present status and trends of prevention and treatment of lysosomal storage
      diseases].

PMID- 19099774
TI  - [Postnatal and prenatal diagnosis of mucopolysaccharidosis type III (Sanfilippo
      syndrome)].
AB  - OBJECTIVE: Mucopolysaccharidosis (MPS) types IIIA, B, C, D are a group of
      autosomal recessive lysosomal storage disorders caused by mutations in one of
      four genes which encode enzyme activities required for the lysosomal degradation
      of heparan sulfate. MPSIIIA and MPSIIIB involve deficiencies of heparan N
      sulfatase (SGSH) and alpha-N-acetylglucosaminidase (NAGLU). MPS IIIA and MPS IIIB
      are more common than MPS IIIC and IIID. The present study aimed to establish two
      enzyme assay methods for SGSH and NAGLU activities for carrying out postnatal and
      prenatal diagnosis of MPSIIIA and IIIB by means of SGSH and NAGLU activity assay
      on plasma, leukocyte, uncultured chorionic villi (CV) and cultured amniotic fluid
      cells (AF cell) using two newly synthesized substrates. Mutation analysis of SGSH
      gene was also performed. METHODS: Two fluorigenic substrate (4-methylumbelliferyl
      alpha-D-N-sulphoglucosaminide.Na and 4-methylumbelliferyl-alpha-N
      acetylglucosaminide) were used for the assay of SGSH and NAGLU activity. SGSH
      activity in leukocyte was determined for diagnosis MPSIIIA proband. NAGLU
      activity was determined in plasma for diagnosis of MPSIIIB proband. Twelve cases
      with MPS III were enrolled in this study, 4 were female and 8 were male, age 3 -
      10 years and were from 10 unrelated families. Eight exons of SGSH gene were
      amplified by PCR. The mutations of the patients were characterized by direct
      sequencing of the amplified DNA fragments. Prenatal diagnosis in 3 pregnancies at
      risk was carried out according to NAGLU activity on uncultured CV at 11th week or
      on cultured AF cell at 18th week of gestation. RESULTS: The SGSH activities in
      leukocyte of normal controls were 4.4 - 8.1 nmol/(17 h.mg protein). The NAGLU
      activity in plasma of normal controls was 33.3 - 62.4 nmol/(4 h.ml). The NAGLU
      activities were 44.9 - 91.7 nmol/(17 h.mg protein) and 53.2 - 82.2 nmol/(17 h.mg
      protein) in CV and cultured AF cells respectively. Five cases of MPS IIIB and 7
      cases of MPS IIIA were diagnosed. The mutation analysis of SGSH gene showed 6
      mutations (G191R, D235N, R377C, E447K, R233X and D219Wfs264X), only one of which
      (D219Wfs264X) has not been previously reported. Prenatal diagnosis was performed
      on 3 pregnancies at risk. NAGLU activity of one affected fetus was 1.5 nmol/(17
      h.mg protein) in AF cell. CONCLUSIONS: The method using synthesized fluorigenic 4
      methylumbelliferyl-substrates were sensitive, rapid and convenient assay of SGSH
      and NAGLU activity and were reliable for early prenatal diagnosis. Mutation
      analysis on MPS IIIA patients suggests new possibilities for molecular diagnosis
      of the disease.

PMID- 19099775
TI  - [Identification and diagnosis of three novel mutations in SLC25A13 gene of
      neonatal intrahepatic cholestasis caused by citrin deficiency].
AB  - OBJECTIVE: Neonatal intrahepatic cholestasis caused by citrin deficiency (NICCD,
      OMIM #605814) is a novel autosomal recessive disease caused by mutations in the
      gene SLC25A13 that encodes for citrin, a liver-type aspartate/glutamate carrier
      located in the mitochondrial inner membrane. SLC25A13 was cloned in 1999 by
      Kobayashi et al at Kagoshima University in Japan, and until now, most of the
      NICCD patients reported in the world were Japanese. Most of the Chinese NICCD
      patients diagnosed by genetic analysis had the same SLC25A13 mutations as
      Japanese, however, in some cases, known mutations were not detected. This
      research aimed to identify novel SLC25A13 mutations in Chinese NICCD patients and
      to explore the experimental conditions for their genetic diagnosis. METHODS:
      Genomic DNA was extracted from blood samples of 3 NICCD patients from Taiwan
      (P757), Guangdong (P1194) and Hebei province (P1443) of China, respectively, and
      all the 18 exons and their flanking sequences of SLC25A13 gene were sequenced.
      Furthermore, the identified novel mutations were diagnosed by amplification with
      PCR, digestion with corresponding restriction endonuclease, and agarose gel
      electrophoresis. RESULTS: Three novel mutations identified in SLC25A13 gene of
      the 3 NICCD patients were an abnormal splicing IVS7-2A > G (P757), a missense
      A541D (c.1622C > A, P1194) and a nonsense R319X (c.955C > T, P1443). The PCR
      restriction fragment length polymorphism (RFLP) procedures for their genetic
      diagnosis were also established, with specific fragments on electrophoresis after
      digestion of the PCR products with three different restriction endonucleases Msp
      I, Hpy188I and Taq I, respectively. CONCLUSIONS: So far as we know, the three
      novel mutations in SLC25A13 gene of Chinese NICCD patients were first identified,
      suggesting that SLC25A13 mutation distributed in Chinese population is somewhat
      different from that in Japanese. Moreover, the PCR-RFLP diagnostic procedures
      established in this research provide valuable tools not only for the genetic
      diagnosis of NICCD but also for further molecular epidemiologic investigations in
      Chinese population.

PMID- 19099777
TI  - [Influence of angiotensin converting enzyme gene insertion/deletion polymorphism
      and beta3-adrenergic receptor gene Trp64Arg polymorphism on fetal growth and
      neonatal insulin sensitivity].
AB  - OBJECTIVE: To understand the influence of angiotensin converting enzyme (ACE)
      gene insertion/deletion (I/D) polymorphism and beta3-adrenergic receptor (beta3
      AR) gene Trp64Arg polymorphism on fetal growth and neonatal insulin sensitivity.
      METHODS: Totally 296 newborn infants were selected into our study and divided
      into 2 groups according to gestational age and birth weight: adequate-for
      gestational-age (AGA) group (222 cases) and small-for-gestational-age (SGA) group
      (74 case). Serum glucose and insulin were examined in the morning of the 3rd day
      before milk. Insulin sensitivity was evaluated by homeostasis model assessment
      (HOMA) equation. beta3-AR gene Trp64Arg polymorphism and ACE gene I/D
      polymorphism (202 cases) were analysed using polymerase chain reaction-restricted
      fragment length polymorphism (PCR-RFLP) technique. Gestational age, birth weight,
      birth weight percentage, serum glucose, insulin and HOMA-IR were compared among
      different genotype groups. Statistical analysis was performed with the SPSS 10.0
      software. RESULTS: No significant difference was found between the serum glucose
      level of SGA group (4.03 +/- 1.05 mmol/L) and AGA group (4.05 +/- 1.14 mmol/L), P
      = 0.008. The serum insulin level (converted into Ln) of SGA group (2.262 +/-
      0.746) was significantly higher than that of AGA group (1.757 +/- 0.805), P <
      0.001. The HOMA-IR (also converted into Ln) level of SGA group (0.217 +/- 0.367)
      was also significantly higher than that of AGA group (0.001 +/- 0.378), P <
      0.001. In the SGA group beta3-AR gene Arg64 allele carriers had higher serum
      insulin and HOMA-IR level (both changed to Ln, 2.654 +/- 0.701, 0.371 +/- 0.338)
      compared with noncarriers (2.074 +/- 0.698, 0.143 +/- 0.360), P < 0.05. The ACE
      gene DD genotype carriers had higher serum insulin and HOMA-IR level (both were
      converted into Ln, 2.19 +/- 0.91, 0.51 +/- 1.01) compared with II (1.77 +/- 0.85,
      0.02 +/- 0.93) and ID genotype group (1.77 +/- 0.83, 0.05 +/- 0.91), P < 0.05.
      The ACE gene DD carriers had lower birth weight percentage compared with II and
      ID genotype group, P < 0.05. When both genes' polymorphisms were taken into
      account, the newborns who had both DD genotype and Arg64 allele had obviously
      higher serum insulin level (Ln, 2.560 +/- 1.160) than the neonates who had only
      one of the polymorphisms mentioned above (1.970 +/- 0.821, 1.992 +/- 0.706) and
      the neonates who had neither of the two polymorphisms (1.683 +/- 0.832), P <
      0.05. The newborns who had both DD genotype and Arg64 allele also had
      significantly higher HOMA-IR level (Ln, 1.042 +/- 1.315) than the neonates who
      had only one of the polymorphisms mentioned above (0.247 +/- 0.710, 0.230 +/-
      0.890) and the neonates who had neither of the two polymorphisms (-0.053 +/-
      0.924), P < 0.05. CONCLUSION: Newborns SGA had impaired insulin sensitivity.
      beta3-AR gene Trp64Arg polymorphism and ACE gene I/D polymorphism are important
      factors that may connect IUGR with insulin resistance syndrome in adulthood.

PMID- 19099776
TI  - [Gene mutation analysis in patients with propionic acidemia].
AB  - OBJECTIVE: Propionic acidemia is a common organic acidemia, caused by deficiency
      of propionyl-CoA carboxylase (PCC), which catalyzes the carboxylation of
      propionyl-CoA to D-methylmalonyl-CoA. PCC is a dodecameric enzyme of alpha-PCC
      and beta-PCC subunits, nuclearly encoded by genes PCCA and PCCB, respectively.
      Mutation in either gene cause propionic acidemia, the PCCA gene is located on
      chromosome 13q32 with 24 exons and the PCCB gene is located on chromosome 3q13.2
      q22 with 15 exons. In this study, we analyzed gene mutations of 11 PCCA and PCCB
      deficient patients from China and to explore the possible mutation spectrum.
      METHODS: All 39 exons of PCCA and PCCB genes in 11 unrelated Chinese PA patients
      were analyzed by polymerase chain reaction (PCR) and direct sequencing. Genomic
      DNA was extracted using phenol-chloroform method from the peripheral blood
      leukocytes of each patient. PCR amplification products were checked by 1.8%
      agarose gel electrophoresis and were subsequently sequenced with ABI 3700
      Automated DNA Sequencer. RESULTS: The authors identified 13 PA mutations, 8
      affecting the PCCA gene, 5 affecting the PCCB gene, including 10 novel mutations
      and 3 previously reported mutations. Three missense mutations (1079T > G, 1102G >
      C and 1850T > C), one splicing mutation (716-2A > G) and one short deletion
      (1863delA) were found in alpha-PCC subunit while three missense mutations (484G >
      A, 601G > A and 1253C > T) and two short insertion-deletions (167-179del13ins1,
      560-561delCCinsT) were found in beta-PCC subunit. The 167-179del13ins1 change was
      identified in two homozygous PA patients, with allelic frequency of 40% in beta
      PCC subunit deficiencies. CONCLUSION: Thirteen mutations were found in 11 Chinese
      PA patients including ten novel mutations. No mutation is predominant in Chinese
      PCCA and PCCB deficient patients.

PMID- 19099778
TI  - [Guidelines for diagnosis and treatment of children with short stature].

PMID- 19099780
TI  - [Recent developments in studies on ion channels and genetics of epilepsy].

PMID- 19099779
TI  - [Insulin resistance and growth].

PMID- 19099781
TI  - [Summary of the 9(th) National Conference on Pediatric Endocrine, Genetic and
      Metabolic Diseases].

PMID- 19099782
TI  - [Summary of the 2007 national conference on pediatric cardiovascular disease].

PMID- 19099783
TI  - [Diagnostic value of fluorescent quantitation PCR for Mycoplasma pneumoniae
      infection].
AB  - OBJECTIVE: Mycoplasma pneumoniae (Mp) infection is one of major causes of
      community-acquired pneumonia. Isolation and culture of Mp are very difficult,
      fluorescent quantitative PCR is a new technique to detect Mp. The aim of this
      study was to explore the diagnostic value of fluorescent quantitation PCR for Mp
      infection. METHOD: Mp-DNA from the deep respiratory tract secretion of children
      suffering from pneumonia was tested by a fluorescent quantitative PCR. Totally
      256 cases who were positive for Mp DNA were enrolled into this study, 164 (64.1%)
      were male, 92 (35.9%) were female; the age ranged from 9 days to 16 years. All
      the patients also had results of Mp-IgM test. These patients were divided into 2
      groups according to the result of Mp-IgM detection, namely, Mp-IgM positive and
      negative groups. Area under the roc curve (Az) was used as the index to evaluate
      the diagnostic value of fluorescent quantitation PCR for Mp detection. The number
      of Mp-DNA copies, age and course of disease of the 2 groups were also compared.
      RESULTS: (1) Diagnostic accuracy of fluorescent quantitative PCR for detecting Mp
      infection was that Az = 0.641. (2) The number of copies of the cases in Mp-IgM
      positive group was 5.42 +/- 1.26 [log(Mp-DNA copy/ml)], while that of Mp-IgM
      negative group was 4.87 +/- 1.29 [log(Mp-DNA copy/ml), t = 3.43, P < 0.05]. (3)
      The age of Mp-IgM positive group was dramatically younger than Mp-IgM negative
      group (P < 0.001). CONCLUSION: The diagnostic accuracy of fluorescent
      quantitative PCR for mycoplasma pneumoniae (Mp) infection is low; however for
      children whose immunologic systems are not fully developed, this technique has
      some diagnostic value, and higher number of Mp-DNA copies may support diagnosis
      of Mp infection.

PMID- 19099784
TI  - [Relationship between methimazole and antineutrophil cytoplasmic antibody
      positive vasculitis].
AB  - OBJECTIVE: To study the relationship between methimazole (MMI) and antineutrophil
      cytoplasmic antibody (ANCA)-positive vasculitis. METHODS: Thirty-three cases with
      Graves' disease were tested for serum ANCA before and after taking MMI. At the
      same time, clinicopathological data of two patients with Graves' disease who had
      antineutrophil cytoplasmic antibody-positive vasculitis during treatment with MMI
      were analyzed. RESULTS: Two patients developed antineutrophil cytoplasmic
      antibody-positive vasculitis during the medication with MMI for 5-6 years; their
      major clinical manifestations were hematuria and renal failure. Renal biology
      showed renal vasculitis and vascular necrosis. The disease was relieved after
      treatment with immunosuppressor. Serum ANCA in the 33 cases was negative before
      taking MMI. In 3 cases serum ANCA became positive after taking MMI for 2 months,
      3 months and 2 years, respectively. The positive rate is 9% (3/33). The major
      finding was microscopic hematuria. ANCA positive rate was significantly higher
      after taking MMI than that before taking MMI (chi2) = 5.3, P < 0.05). Microscopic
      hematuria disappeared after general treatment. CONCLUSION: There may be a
      relationship between methimazole and development of antineutrophil cytoplasmic
      antibody-positive vasculitis. Renal impairment can occur. The signs and symptoms
      of the vasculitis can disappear after proper treatment.

PMID- 19099785
TI  - [Clinical characteristics of 41 children with cyclic vomiting syndrome].
AB  - OBJECTIVE: To analyze the clinical characteristics of children with cyclic
      vomiting syndrome (CVS), summarize the experience for twelve years, and improve
      awareness, diagnosis and treatment level of CVS. METHODS: The clinical data and
      results of long-term follow-up of the children with CVS seen from 1994 to 2007 in
      our department were analyzed. RESULTS: Forty-one children were enrolled in the
      study, 21 were male, and 20 female, mean age was 8 years, mean age of onset was 4
      years, mean interval from onset to proper diagnosis was 4 years; 13/41 and 20/41
      patients had family history of migraine and motion sickness, 20/41 patients had
      triggers, such as upper respiratory tract infection, diet, and mental/emotional
      factor. Vomiting lasted for days, during the periods between the episodes of
      vomiting the children were completely healthy. The intervals of most patients
      were 2 to 8 weeks, and in 12/41 patients the episodes started at early morning.
      The peak number of emesis per hour exceeded six in 23/41 children. The episodes
      were characterized by a pattern of sudden onset and sudden ending. All patients
      showed depressed, social withdrawal, intractable nausea and anorexia. Associated
      symptoms and signs include pallor, excess salivation, hypertension, headache,
      photophobia, and abdominal pain. Electroencephalogram of 13/33 patients were
      slightly abnormal. Electrogastrogram showed dysrhythmia and gastrointestinal
      motility were abnormal during the period of onset and normal during complete
      remission. Eleven of the 41 of patients were treated as epilepsy, and 9 patients
      were diagnosed as esophageal hiatal hernia and 4 superior mesenteric artery
      compression syndrome and had surgery before the diagnosis was made. Eight
      patients diagnosed from 1994 to 2000 were followed up for ten years in average, 3
      patients were treated with doxepin and alprazolanic, and were cured after 2.2
      (1.0 - 4.0) years; and five patients who did not use any medicine recovered 7.7
      (4 - 10) years later. Fourteen children diagnosed from 2001 to 2007 were followed
      up for longer than one year, 9 patients were treated with valproate, doxepin,
      cyproheptadine, and recovered 2.3 (1 - 4) years later; 5 patients without
      treatment recovered 1.9 (1 - 3) years later. CONCLUSIONS: The diagnosis must be
      based on the special manifestation of CVS, including intervals during which the
      patients are completely healthy, and the systemic diseases which can cause CV
      should be excluded. Most patients get better as they grow up. Therapeutic
      strategies may include combined use of neuroleptics, thymoleptics and anti
      migraine when the episodes occur frequently and when there is growth retardation.
      Supportive care includes intravenous fluids and symptomatic treatment during an
      episode.

PMID- 19099786
TI  - [Randomized controlled multi-center trial for treatment of varicella in pediatric
      patients with hydrochloride valacyclovir].
AB  - OBJECTIVE: To evaluate the efficacy and safety of hydrochloride valacyclovir in
      treatment of varicella in pediatric patients between April 2006 and March 2007.
      METHODS: A randomized controlled multi-center clinical trial was conducted in 5
      pediatric centers, i.e., Children's Hospital of Fudan University, Children's
      Hospital of Zhejiang University, Children's Hospital of Nanjing Medical
      University, Pediatric Department of Tongji Hospital of Tongji Medical College,
      Huazhong University of Science & Technology and Children's Hospital, Chongqing
      University of Medical Sciences. Patients who were clinically diagnosed as
      varicella without any complications and were beyond 3 years of age were enrolled
      into the study from the out-patient clinics. The subjects were divided into two
      groups randomly, one was treated with hydrochloride valacyclovir, the other with
      ribavirin. There were 128 cases in the group treated with hydrochloride
      valacyclovir and 132 cases in control group treated with ribavirin. The treatment
      duration of two groups was five days. The clinical efficacy and safety were
      evaluated after the first day and the fourth day of the treatment and within
      three days after the end of the treatment. The clinical efficacy was assessed by
      efficacy index. RESULTS: (1) The efficacy index on the fourth day of the therapy
      (0.80 +/- 0.24) in the valacyclovir group was significantly higher than that of
      ribavirin control group (0.59 +/- 0.37) (t = 5.42, P < 0.01). The efficacy index
      at the end of the treatment (0.86 +/- 0.14) in the hydrochloride valacyclovir
      group was also significantly higher than that (0.70 +/- 0.30) of the ribavirin
      control group (t = 5.43, P < 0.01). (2) In the valacyclovir and ribavirin groups,
      the effective rates on the fourth day of the therapy were 94.53% and 72.7%
      respectively (chi2) = 22.38, P < 0.01). The effective rates at the end of the
      therapy were 99.2% and 88.6%, respectively (chi(2) = 12.60, P < 0.01). The rates
      of cure of the two groups were 33.6% and 25.0% (chi2) = 2.32, P > 0.05). (3) No
      severe adverse drug reactions were observed in any of the two groups.
      CONCLUSIONS: The hydrochloride valacyclovir was safe, reliable and convenient in
      treatment of uncomplicated varicella in children.

PMID- 19099788
TI  - [Changes of u-PA and PAI-1 expression in the lung tissue of neonatal rats after
      inhaling high concentration oxygen].
AB  - OBJECTIVE: Arrested lung development and lung fibrosis are characteristic
      pathological changes in chronic lung disease (CLD). Therefore, the role of
      extracellular matrix (ECM) remodeling in lung fibrosis has been emphasized
      recently. Plasmin system is also an important factor to modulate ECM degradation
      and matrix metalloproteinase (MMP) system. In this study, the authors established
      an animal model of CLD induced by inhaling high concentration oxygen (hyperoxia)
      to investigate the changes and functions of urokinase-plasminogen activator (u
      PA) and plasminogen activator inhibitor-1 (PAI-1) in CLD. METHODS: Full-term
      newborn rats were continuously exposed to oxygen (0.90 - 0.95 O(2)) or room air
      within 12 h after birth. On day 1, 3, 7, 14, 21 in hyperoxia groups and air
      controls, lung pathology in newborn rats were observed. The changes of u-PA and
      PAI-1 protein and mRNA expression were measured by Western blotting and RT-PCR.
      RESULTS: (1) The pathological findings of the lung tissue: on day 3, there was a
      few inflammatory cells exuded out, bleeding, edema, and interstitial cells
      increased in hyperoxia group. On day 7 and thereafter, the terminal air space
      size of the oxygen-exposed rat became large, there was inflammatory response and
      more interstitial cells, interstitium was thicker, and collagen deposited. (2) u
      PA expression: On day 3, the u-PA protein expression increased in hyperoxia group
      compared with controls (115.52 +/- 7.10 vs. 96.51 +/- 6.33), P < 0.01. On day 7
      to day 21, u-PA protein expression (97.66 +/- 7.98, 99.91 +/- 7.60, 103.23 +/-
      6.24) was lower than in the control groups (112.43 +/- 6.01, 123.25 +/- 8.35,
      103.23 +/- 6.24), P < 0.05, < 0.01 and < 0.01, respectively. u-PA mRNA increased
      on d 3 in hyperoxia group compared with controls (1.18 +/- 0.07 vs. 0.99 +/-
      0.05), P < 0.01. On d 7 to 21, mRNA expression (1.01 +/- 0.06, 1.10 +/- 0.12,
      1.27 +/- 0.06) was lower than that in the controls (1.15 +/- 0.08, 1.51 +/- 0.32,
      1.60 +/- 0.24) too, P < 0.01. (3) PAI-1 expression: From d 7 to 21 of oxygen
      exposure, PAI-1 protein expression (147.83 +/- 12.27, 149.07 +/- 11.17, 161.42 +/
      13.08) increased compared with the controls (116.18 +/- 10.67, 113.73 +/- 15.58,
      126.60 +/- 8.59), P < 0.01, < 0.05 and < 0.01, respectively. mRNA expression
      (1.49 +/- 0.28, 1.46 +/- 0.31, 1.51 +/- 0.33) increased compared with the control
      group (0.94 +/- 0.01, 0.94 +/- 0.03, 0.98 +/- 0.03), P < 0.05, < 0.01 and < 0.05,
      respectively. CONCLUSIONS: In the early stage of hyperoxic exposure, the balance
      of u-PA/PAI-1 mRNA and protein increased, plasmin and degradation activity
      increased, which may increase the degradation of ECM in lung base membrane.
      During the middle and late stage, the expression of u-PA/PAI-1 mRNA and protein
      decreased, plasmin and degradation activity were lower, in parallel to thicker
      interstitium, suggesting that the imbalance of u-PA/PAI-1 may also play a role in
      lung fibrosis in CLD induced by hyperoxia.

PMID- 19099789
TI  - [Effects of potassium channel activators on transient inward current in guinea
      pig ventricular myocytes].
AB  - OBJECTIVE: To investigate the mechanism of ATP-sensitive potassium channel
      (K(ATP)) activator cromakalim (CRK) on action potentials and transient inward
      current (I(ti)) in isolated guinea pig papillary and ventricular myocytes and to
      explore the mechanisms of effects of I(ti) and K(ATP) treatment in idiopathic
      ventricular tachycardia. METHODS: The whole-cell patch clamp recording technique
      was used to detect the action potentials and I(ti) and K(ATP) current alterations
      during the stimulated and triggered activity. Myocytes were isolated from guinea
      pig ventricle by enzyme digestion. The experiment was divided into four groups:
      (1) Control; (2) Control + Ouabain; (3) Control + CRK; (4) Control + Ouabain +
      CRK. (5) Control + Ouabain + CRK + glibenclamide (GLB). The action potential of
      guinea pig papillary muscles was measured by using standard microelectrode. The
      parameters in the experiment included the amplitude (APA), resting potentials
      (RP), action potentials duration (APD), as well as maximum rise of the action
      potential (Vmax). RESULTS: (1) When the guinea pig ventricular papillary myocytes
      were pretreated with Ouabain 0.5 micromol/L, APD prolonged significantly,
      especially APD(20), APD(50), APD(90). Delayed after depolorazion (DAD) and
      triggered activity were elicited. I(ti) currents and DAD as well as triggered
      activity increased. I(ti) current was (126.9 +/- 10.8) pA, lagT (1173.0 +/- 70.9)
      ms (n = 10, P < 0.01). (2) When guinea pig ventricular myocytes were pretreated
      with CRK (10 micromol/L), APD was shortened and the amplitude of DAD was lowered.
      The coupling time in CRK group was significantly prolonged compared with Ouabain
      group (n = 10, P < 0.01). (3) CRK 50 micromol/L pretreatment of the ventricular
      myocytes led to an increase of K(ATP) up to (342 +/- 89) pA, which was
      statistically significant as compared with the control group (P < 0.01). ATP
      sensitive potassium channel blocker glibenclamide (10 micromol/L) could
      antagonize the effects of CRK on APD and I(ti) currents. CONCLUSION: CRK might
      reduce the toxic effect of Ouabain on cardiomyocytes, shorten APD, terminate DAD
      and trigger excitation, and have protective effect on cardiomyocytes. The effects
      of CRK, may be associated with the inhibiting I(ti) current and increasing
      K(ATP).

PMID- 19099790
TI  - [Clinical and etiological analyses of acute lower respiratory tract infections in
      children in Kunming area].

PMID- 19099791
TI  - [Effect of ethyl nitrite versus inhaled nitric oxide in a rat model of acute
      pulmonary hypertension].

PMID- 19099794
TI  - [Minor injury and basal ganglia calcification may be the risk factors of
      children's stroke].

PMID- 19099792
TI  - [Analysis of the families and the clinical phenotypes of the generalized epilepsy
      associated with adjunct febrile seizure].

PMID- 19099795
TI  - [Congenital muscular dystrophy complicated with tetanized spinal column in a
      case].

PMID- 19099796
TI  - [Neonatal Ehlers-Danlos syndrome in a case].

PMID- 19099797
TI  - [Treatment of fungal septicemia in a premature infant with caspofungin].

PMID- 19099799
TI  - [Promote high quality clinical research to fulfill the commitment for children's
      health].

PMID- 19099800
TI  - [Pay much attention to prevention and treatment of iron deficiency anemia in
      children].

PMID- 19099801
TI  - [The question on closure time of fontanel in infants and young children and the
      answer].

PMID- 19099802
TI  - [Characteristics of T cell receptor beta gene rearrangements and its role in
      minimal residual disease detection in childhood T-cell acute lymphoblastic
      leukemia].
AB  - OBJECTIVE: To explore the characteristics of T cell receptor beta (TCRbeta) gene
      rearrangements in children with T-cell acute lymphoblastic leukemia (T-ALL) and
      establish a system of quantitative detection of MRD with real-time quantitative
      (RQ-PCR) targeted at TCRbeta gene rearrangement. METHODS: Multiplex polymerase
      chain reaction (PCR) designed by BIOMED-2 was used to detect TCRbeta gene
      rearrangements in the bone marrow samples of 26 children with T-ALL. Sequence of
      junction region were then compared and analyzed in IMGT database. Allele specific
      oligonucleotide (ASO) upstream primers were designed complementary to the V-D-J
      or D-J junctional region of TCRbeta gene rearrangements. Samples at diagnosis
      were serially diluted in DNA obtained from mononuclear cells (MNC) from a pool of
      20 healthy donors to generate the patient specific standard curves. Subsequently,
      a TCRbeta RQ-PCR assay to quantify MRD with germline Jbeta primer/probe
      combinations was applied in six patients. To check the quantity and quality of
      DNA, the investigators used RQ-PCR analysis for the N-ras gene. RESULTS: Clonal
      rearrangements were identified in 92.3% childhood T-ALL (Vbeta-Dbeta-Jbeta
      rearrangements in 84.6%, Dbeta-Jbeta rearrangements in 50%). Comparative sequence
      analysis of 42 TCRbeta recombinations revealed two downstream Vbeta families
      (BV5, BV6) were preferentially used. The segment Jbeta2.7 in childhood T-ALL was
      preferentially used. Jbeta1.3, Jbeta2.4, and Jbeta2.6 were not found to be used.
      The slope of the standard curves was from -3.54 to -3.37 and the intercepts were
      from 19.35 to 20.51. The correlation coefficients of all 6 standard curves were
      excellent (> or = 0.98). All the RQ-PCR quantitative range reached 10(-4). MRD
      analysis of follow up samples showed that MRD increased before relapse.
      CONCLUSION: RQ-PCR analysis of TCRbeta gene rearrangements was highly sensitive
      and specific, it will be of high value for future T-ALL MRD studies. And
      quantitative and serial study of MRD may be of prognostic importance.

PMID- 19099803
TI  - [Preparation of the immunotoxin 2E8-norcantharidin and its targeting killing
      effect in vitro].
AB  - OBJECTIVE: Monoclonal antibody (mAb) conjugated with certain toxin to generate
      immunotoxin bears an important and promising effect as a new therapy for patients
      with hematopoietic malignancies. However, most toxic moieties conjugated with
      antibody proteins reported in the literature were toxic proteins which presented
      immunogenicity to patients capable of inducing anti-toxin antibody.
      Norcantharidin (NCTD) is a small molecule toxin. It does not have the
      immunogenicity to human body so that it bears a promising potential for
      development of new targeting drug. In this study, a new clone of self-made anti
      CD19 mAb named ZCH-4-2E8 conjugated with NCTD was used to investigate its
      targeting efficacy against CD19+ lymphoid malignant Nalm-6 cells in vitro to
      provide the experimental data for the further development of this new targeting
      agent. METHODS: A monoclonal antibody named 2E8 was prepared from mouse ascites
      and purified by gel chromatography. The purity of the antibody protein was
      checked by SDS-PAGE assay. Immunotoxin 2E8-NCTD was successfully generated
      through conjugating CD19 mAb protein and Norcantharidin by the activated ester
      method. The binding activity of the immunoconjugate (2E8-NCTD) against CD19
      antigens on cell surface and the expression levels of CD19 antigens on Nalm-6 and
      K562 cells were examined by flow cytometry. Comparisons of the inhibitory effects
      among PBS, purified 2E8 antibody, norcantharidin and immunotoxin 2E8-NCTD groups
      on cell growth of either Nalm-6 cells or K562 cells were made. RESULTS: The
      purity of the purified 2E8 antibody was higher than 99.00% demonstrated by SDS
      PAGE assay. 2E8 antibody in the supernatant reacted with 99.34% of Nalm-6 cells,
      while only 0.98% of K562 cells reacted with this antibody. The newly generated
      immunotoxin (2E8-NCTD) had a positive rate of 99.90% on Nalm-6 cells with little
      reduction of binding activity. From the in vitro study, both 2E8-NCTD and
      norcantharidin were shown to have significant inhibitory effects on the growth of
      CD19+ Nalm-6 cells (P < 0.001), while the purified 2E8 antibody did not show any
      significant influences on the growth of Nalm-6 cells. Since no significant
      inhibitory effects were identified among immunotoxin 2E8-NCTD, 2E8 antibody and
      control groups on CD19(-) K562 cells, a significant targeting effect of the 2E8
      NCTD against Nalm-6 cells was confirmed. CONCLUSIONS: The immunotoxin 2E8-NCTD
      was successfully synthesized by activated ester method with an excellent
      targeting killing effect on CD19+ Nalm-6 leukemia cells in vitro, which provides
      some experimental data for the further development of this new targeting agent.

PMID- 19099804
TI  - [Efficacy and prognosis analysis in 188 children with acute lymphoblastic
      leukemia of China].
AB  - OBJECTIVE: To analyze the therapeutic effect and the influencing factors of event
      free survival (EFS) of childhood acute lymphoblastic leukemia (ALL) in Xiangya
      Hospital of Central South University and the First Affiliated Hospital of Guangxi
      Medical University. METHODS: All the patients adopted chemotherapy according to
      therapeutic guideline revised by the Subspecialty Group of Hematology, The
      Society of Pediatrics, Chinese Medical Association for the second-time in 1998
      (the Rongcheng ALL-98 Protocol). Kaplan-Meier method was used to estimate the
      survival rates of 188 patients who received therapy with good compliance. The
      differences of EFS between groups were assessed by Log-rank test. The independent
      influencing factors on EFS were analyzed by the Cox proportional hazards
      regression model. RESULTS: After receiving inductive treatment, 354 of 374
      (93.6%) patients demonstrated a complete remission; 188 patients who received
      complete courses of treatment with good compliance showed (68.1 +/- 5.6)% five
      year EFS. Meanwhile, the five-year EFS in standard-risk (SR) group and high-risk
      (HR) group were (75.2 +/- 6.0)% and (47.6 +/- 11.6)%, respectively. The total
      relapse rate was 10.6% and the median time to relapse was 13 months. Twenty-nine
      of 188 patients (15.4%) were dead, and 13 patients (7.0%) died from treatment
      related complications. Independent adverse prognostic factors included risk
      grouping, t (9; 22)/bcr-abl gene and leukocyte count. CONCLUSIONS: The total EFS
      of childhood ALL patients treated with Rongcheng ALL-98 Protocol in two hospitals
      was close to 70%. Therefore, it is necessary to evaluate risk factors and
      consider the grouping in more detail to reduce the treatment-related mortality
      and to increase the compliance of treatment which can ultimately improve the EFS.

PMID- 19099805
TI  - [Recommendations for prevention and treatment of iron deficiency and iron
      deficiency anemia in children].

PMID- 19099806
TI  - [Summary of the panel discussion on the recommendations for prevention and
      treatment of iron deficiency and iron deficiency anemia in children].

PMID- 19099807
TI  - [Progresses in prevention and treatment of iron deficiency and iron deficiency
      anemia in children].

PMID- 19099808
TI  - [Neurogenic pulmonary edema].

PMID- 19099809
TI  - [Subcutaneous panniculitis-like T-cell lymphoma in a case].

PMID- 19099810
TI  - [Three cases of enterovirus 71 infection with pulmonary edema or pulmonary
      hemorrhage as the early clinical manifestation].
AB  - OBJECTIVE: To recognize the clinical features of the enterovirus 71 (EV71)
      infection with pulmonary edema or pulmonary hemorrhage as a fulminant and often
      fatal illness. METHODS: We retrospectively reviewed the medical records of the
      three cases with EV71 infection for clinical manifestation, laboratory data,
      medications, outcome etc. RESULTS: All the cases were infants and they all died.
      These infants had no skin or mucosal lesions, however, they had sudden onset of
      cyanosis and tachypnea 1 to 2 days after the onset of the febrile disease with
      vomiting. All these 3 cases were misdiagnosed and were treated for shock on
      admission. Pulmonary hemorrhage was not considered in any of the cases on
      admission. All the cases received tracheal intubation when foamy secretions were
      discharged from mouth and nose of the patients and notable cyanosis was noted.
      After intubation, all had pink foamy fluid flew out from the endotracheal tube.
      The patients had hyperglycemia and limb weakness, two had tachycardia, and
      hypertension was found in one case. Chest X-ray showed bilateral or unilateral
      widespread air space opacity, but the cardiac size and shape were normal. All the
      patients had leucocytosis. EV71 infection was confirmed by detection of specific
      sequences of the virus in throat swab and tracheal secretions samples and in one
      case in cerebrospinal fluid sample. CONCLUSION: Pulmonary edema or pulmonary
      hemorrhage occurred in the 3 cases with EV71-infected infants. The initial
      presentation was often nonspecific with fever and vomiting, and sudden
      appearances of cyanosis, tachypnea, tachycardia, hypertension or hypotension,
      limb weakness may suggest pulmonary edema or hemorrhage. Excessive fluid
      resuscitation may deteriorate the illness, on the contrary, fluid restriction and
      inotropic agents, and early intubation with positive pressure mechanical
      ventilation may be the proper treatment.

PMID- 19099811
TI  - [Expert's comment].

PMID- 19099812
TI  - [Clinical analysis of 139 cases of primary vesicoureteric reflux in children].
AB  - OBJECTIVE: To analyze the clinical features, renal damage and prognosis of
      primary vesicoureteric reflux (VUR) in children, hoping to give more attention to
      early recognition and treatment of the disease. METHODS: Between June 1995 and
      December 2006, 974 patient were admitted in our hospital because of urinary tract
      infection (UTI), 139 primary VUR children were enrolled in the retrospective
      study. VUR grades, renal scar development, renal ultrasound and urinalysis were
      evaluated. RESULTS: The incidence of VUR in UTI children was 14.3% (139/974),
      however, the incidence in infants and toddlers (younger than two years of age)
      was 17.2% (79/458), which was greatly higher than that in school children. Of the
      139 children, 79(56.8%) were younger than two years and the number of boys was
      much larger than that of girls (P = 0.001). Bilateral reflux was found in 69
      cases, unilateral in 70 cases; the percentages of mild reflux (grade I-II) was
      19.7% (41/208), moderate reflux (grade III) was 35.6% (74/208), severe reflux
      (grade IV-V) was 44.7% (93/208). Dimercaptosuccinic acid (DMSA) scanning was
      performed for 135 patients, and renal scar was found in 37% (50/135), and the
      rate of scar in infants was the highest (42.4%), and 30 (60%) patients with renal
      scar were younger than two years of age. Among them five patients were found to
      have renal scar during the follow up period, four of them were younger than two
      years. The rate of renal scar in moderate and severe reflux was much higher than
      that in mild reflux cases, the risk of occurring renal scar would increase with
      its severity of reflux (P < 0.001). The sensitivity and specificity of renal
      ultrasound in suggesting VUR were 24.8% and 94.3%, respectively. The positive
      outcome of urinary N-acetyl-beta-glucosaminidase was a bit high, but there were
      no associations between renal scar and urinary microprotein (P > 0.05). Thirty
      one cases were followed up for long time (> 1 year); and 90% of urinary infection
      was controlled and in 44.4% of patients VUR disappeared with medical treatment.
      No child had decreasing renal function in follow-up period. CONCLUSION: Children
      with primary VUR need early diagnosis and treatment. Insisting on normal therapy
      and long-term follow-up will protect renal function effectively.

PMID- 19099813
TI  - [Application of nested PCR and sequencing technique to detect point mutations of
      the 23S rRNA gene of Mycoplasma pneumoniae].
AB  - OBJECTIVE: To establish a quick method to detect drug resistance of Mycoplasma
      pneumoniae (MP) and study the condition of drug resistance in MP infection.
      METHODS: MP 23S rRNA target gene in throat swab specimens from 200 patients with
      suspected MP infection was detected by using nested PCR and DNA sequencing. The
      result of 23S rRNA gene detection was confirmed by MP isolation and drug
      susceptibility test in vitro for reliability. RESULTS: Of the 200 clinical
      specimens, 64 were proved to be positive for MP through MP-IgM antibody, MP
      specific 16S rRNA nested PCR and MP isolation . The 23S rRNA gene was amplified
      and the gene sequence was compared with MP reference strain in Genbank, 26 were
      identical to the reference strain, 38 had a point mutation in 23S rRNA. Among
      them, 35 had A to G mutation at position 2063, 1 had A to C mutation at position
      2063 and 2 had A to G mutation at position 2064, the percentage of drug
      resistance was 59.4%. The sensitivity of the gene detection method was 10(2)
      ccu/ml and it was confirmed to be reliable by MP isolation and drug
      susceptibility test. CONCLUSIONS: The gene detection method could detect MP drug
      resistant gene directly from clinical specimen, which has the advantages of high
      specificity, high sensitivity and quickness. It is of great significance for
      diagnosis of MP infection because MP isolation is difficult and time-consuming.

PMID- 19099814
TI  - [Clinical and mutational study of a Chinese infant with isovaleric acidemia].
AB  - OBJECTIVES: Isovaleric acidemia (IVA) is an autosomal recessive inborn error of
      leucine metabolism caused by a deficiency of the mitochondrial enzyme isovaleryl
      CoA dehydrogenase (IVD) resulting in the accumulation of derivatives of
      isovaleryl-CoA. IVA is considered to be a severe, potentially life-threatening
      disorder that manifests with acute neonatal encephalopathy in approximately half
      of affected individuals, and recurrent episodes of vomiting, lethargy, coma and
      varying degrees of developmental delay in the other half of patients. This study
      was conducted to investigate the clinical features and IVD gene mutations of a
      Chinese patient with IVA. METHODS: The clinical features, routine laboratory
      data, blood amino acid and acylcarnitine profiles and urinary organic acid
      profiles of a patient with IVA were reviewed. Whole coding exons of IVD gene were
      PCR-amplified for DNA sequencing. The novel mutation c.466G > C (G127A) was
      confirmed by RFLP with restriction endonuclease Hph I. RESULTS: The patient was a
      2 year and 7 month-old boy. At 3 days of age, he began to show severe vomiting
      and acidosis. He was treated with pyloromyotomy at 10 days of age. His recurrent
      vomiting was not ameliorated until beginning transition to a diet that included
      more carbohydrate from 4 months. He had 3 recurrent severe vomiting and acidosis
      later and showed obvious psychomotor retardation. Blood spot acylcarnitine
      profiles by MS-MS demonstrated an elevation of C5-carnitine with a peak
      concentration of 12.89 micromol/L (< 0.5 micromol/L). Organic acid analysis of
      urine by GC-MS revealed a relatively high level of isovaleric glycine. Mutational
      analysis of the patient's IVD gene revealed heteroallelic mutations of c.149G > A
      (R21H) and c.466G > C (G127A) which is a novel missense mutation. G127A mutation
      was not detected in any of 50 normal controls. CONCLUSIONS: From the clinical
      course, obvious elevation of blood C5-carnitine and urine isovaleric glycine,
      this patient's disorder should be classified as "metabolically severe" type of
      IVA which suggest that c.466G > C (G127A) mutation could severely damage the
      function of the IVD protein. To our knowledge, this is the first characterization
      of IVD gene mutations in the mainland of China.

PMID- 19099815
TI  - [Effect of intrauterine hepatitis B virus infection on peripheral blood
      mononuclear cells interferon-gamma and interleukin-4 in newborns].
AB  - OBJECTIVE: To observe the effect of intrauterine hepatitis B virus (HBV)
      infection on peripheral blood mononuclear cells function of secreting interferon
      gamma and interleukin-4. METHODS: Pregnant women were systematically screened for
      HBsAg and HBeAg when attending the antenatal clinic at the Qinhuangdao Maternal
      and Child Health Hospital. Totally 67 pairs of mothers and infants were enrolled
      into this study after obtaining the women's consent. Venous blood samples were
      collected from the infants within 6 hours after birth and before HBIG injection
      and HBVac immunization. Blood sample was taken from the mother at or after the
      time when the infant was born. HBV DNA in plasma and PBMC from mothers and their
      newborns were examined using polymerase chain reaction (PCR). According to HBV
      DNA in PBMC of newborns, they were divided into two groups. The PBMCs isolated
      from newborn were cultured with purified HBsAg or phytohemagglutinin (PHA). The
      supernatant interleukin-4 and interferon-gamma level was measured by using enzyme
      linked immunosorbent assay (ELISA). RESULTS: In 19 newborns PBMC was positive for
      HBV DNA. Maternal PBMC HBV DNA positivity was associated with high rate of
      intrauterine HBV infection in the infants (chi2 = 7.58, P < 0.01). Compared with
      the infants whose PBMC HBV DNA was negative, the infants with PBMC positive for
      HBV DNA expressed a lower level interferon-gamma secretion after purified HBsAg
      stimulation (t = 4.71, P < 0.01), however, no significant difference was seen
      after PHA stimulation (t = 1.21, P > 0.05). The supernatant IL-4 level detected
      after stimulation with purified HBsAg was higher in the newborns whose PBMC HBV
      DNA was positive as compared with those negative for PBMC HBV DNA (t = -8.51, P <
      0.05). The level of IL-4 did not show any significant difference after
      stimulation with PHA between the PBMC HBV DNA negative and positive groups (t = 
      2.40, P > 0.05). CONCLUSION: Infection with HBV of maternal PBMC is responsible
      for perinatal newborn's PBMC HBV infection and it may be an important route of
      HBV vertical transmission. Infants whose mothers were positive for HBsAg, HBeAg
      and HBV DNA were at extraordinarily high risk for hepatitis B virus infection.
      PBMC infected with HBV could influence the status of humoral and cellular
      immunity resulting in persistent HBV infection and recurrent mother to infant
      transmission of HBV. Low responses of interferon-gamma and high interleukin-4
      transcription upon specific stimulation exist in infants whose PBMC were positive
      for HBV DNA in uterus may contribute to immune tolerance to HBV.

PMID- 19099816
TI  - [Role of c-Jun N-terminal kinase signal transduction pathway in the course of
      airway remodeling of asthma rat].
AB  - OBJECTIVE: To study the role of c-Jun N-terminal kinase (JNK) signal transduction
      pathway in the course of asthma airway remodeling, to explore whether IL-1beta
      participates in asthma airway remodeling mediated by JNK signal transduction
      pathway. METHODS: Totally 72 male Sprague-Dawlay rats (6 - 8 weeks old, weighing
      about 120 g) were randomly divided into control groups (36 rats) and asthma
      groups (36 rats). The rats were sensitized for inducing asthma by intraperitoneal
      injection of ovalbumin and AL(OH)3 and were repeatedly exposed to aerosolized
      ovalbumin for 4, 8, 12 weeks (A4, A8, or A12 group), each had 12 rats, and
      correspondingly control rats were intraperitoneally injected with 0.9% NaCl, then
      were repeatedly exposed to 0.9% NaCl for 4, 8, 12 weeks (C4, C8, or C12 group),
      each had 12 rats. The ultrastructural changes of pulmonary tissues were observed
      by transmission electron microscope (TEM). The total bronchial wall thickness
      (Wat) and the airway smooth muscle thickness (Wam) were measured by an image
      analysis system. The concentrations of IL-1beta in serum and bronchoalveolar
      lavage fluid (BALF) were tested by a "sandwich" ELISA. The protein expressions of
      P-JNK and P-c-Jun were detected by immunohistochemical technique. Lung tissue
      extracts were analyzed for phosphorylation of JNK by Western blotting. Linear
      correlation analysis showed the correlation between Wat and P-JNK protein, Wam
      and P-JNK protein, levels of IL-1beta in serum and P-JNK protein, levels of IL
      1beta in BALF and P-JNK protein. RESULTS: In asthma groups, TEM showed alveolar
      septal proliferation and alveolus type II epithelial cells swelling. Wat and Wam
      in all asthma groups were significantly higher than those in corresponding
      control groups (P < 0.01, respectively), and compared with group A4 and group A8,
      Wat and Wam of group A12 significantly increased (P < 0.01). The concentrations
      of IL-1beta in serum and BALF of asthma groups were all significantly higher than
      those of the corresponding control groups (P < 0.01, respectively), and compared
      with group A4 and group A8, the concentrations of IL-1beta in BALF of group A12
      significantly increased (P < 0.01 or P < 0.05), but the levels of IL-1beta in
      serum were not significantly different among them (P > 0.05). Mean absorbance
      values (by immunohistochemistry) of P-JNK and P-c-Jun in asthma groups were
      significantly higher than those in corresponding control groups (P < 0.01,
      respectively), and compared with group A4 and group A8, those of group A12
      significantly increased (P < 0.01 or P < 0.05). The absorbance (by Western Blot)
      of P-JNK in A4, A8, A12 group was significantly higher than that in C4, C8, C12
      groups (P < 0.01, respectively), and compared with group A4, that of P-JNK of A12
      significantly increased (P < 0.01), and compared with group A8, there was no
      significant difference (P > 0.05). Strong positive correlations were found
      between Wat or Wam and P-JNK (r = 0.823 and r = 0.818, P < 0.01, respectively, n
      = 68) and between P-JNK and concentration of IL-1beta in serum or BALF (r = 0.717
      and r = 0.803, P < 0.01, respectively, n = 68). CONCLUSIONS: The expression of P
      JNK and its downstream P-c-Jun in rats of asthma airway remodeling is increased,
      which implicates that JNK signal transduction pathway plays an important role in
      the course of asthma airway remodeling. IL-1beta participates in asthma airway
      remodeling possibly partly through activating JNK signal transduction pathway.

PMID- 19099817
TI  - [Expression of HoxB5 mRNA and their effect on lung development in premature rats
      with hyperoxia-induced chronic lung disease].
AB  - OBJECTIVE: Resolution of alveolar damage after lung injury requires finely
      orchestrated processes that include coordinated and effective tissue
      reconstruction to reestablish a functional barrier. Reconstitution of denuded
      type I alveolar epithelial cell that undergo apoptotic and necrotic death after
      lung injury is required in many pulmonary diseases. Disruption of distal airway
      development and type II-type I alveolar epithelial cell differentiation after
      lung injury and disordered repair of the alveolus after injury is one of the
      predominant pathological characteristics of chronic lung disease (CLD) of
      premature infants. HoxB5 belongs to the Hox gene family encoding transcription
      factors known for their role in skeletal patterning and the elaboration of
      organs. HoxB5 is required for embryonic respiratory tract morphogenesis. The
      present study aimed to test the hypothesis that HoxB5 may participate in the
      etiology of CLD and to understand possible mechanism. METHODS: Premature rat pups
      were taken out surgically at gestational age 21 d. CLD was induced by hyperoxia
      exposure in neonatal premature rats. Eighty premature rats were randomly exposed
      to hyperoxia (FiO2 = 0.90, CLD group) and to room air (FiO2 = 0.21, control
      group) (n = 40 each). Lung specimens were obtained respectively on days 1, 3, 7,
      14 and 21 after exposure. Histopathologic changes was assayed after hematoxylin
      and eosin (HE) staining and pulmonary development was evaluated by lung
      coefficient and radical alveolar counts (RAC), dynamic changes of RAC were
      observed; and the expression of HoxB5, AQP-5, and SP-B mRNA were assayed by
      reverse transcription polymerase chain reaction (RT-PCR). RESULTS: There were no
      significant differences in the RAC and the expression level of HoxB5, AQP-5, and
      SP-B mRNA between the CLD and the control groups within 3 days after birth (P >
      0.05). However, compared to the control group, the RAC of the CLD group was
      reduced (6.35 +/- 0.83 vs. 7.67 +/- 0.52), and the expression of HoxB5 (0.98 +/-
      0.14 vs. 1.20 +/- 0.16), AQP-5 (0.78 +/- 0.11 vs. 1.04 +/- 0.19) mRNA were
      significantly lower (P < 0.05), while the expression of SP-B mRNA was increased
      on the 7th day (P < 0.05). On the 14th day, the RAC and the expression of HoxB5,
      AQP-5 mRNA of CLD group were significantly lower than those of the control group
      (P < 0.05), and the expression of SP-B mRNA continued to increase (P < 0.05). On
      the 21st day, the expression of HoxB5, AQP-5 mRNA decreased to the nadir (0.64 +/
      0.11 vs. 1.18 +/- 0.13 and 0.67 +/- 0.12 vs. 0.97 +/- 0.01, respectively) (P <
      0.01), on the same day the expression of SP-B mRNA reached to the pinnacle (1.43
      +/- 0.07 vs. 1.12 +/- 0.09) (P < 0.01). The expression of HoxB5 mRNA was
      positively correlated with RAC in the CLD group (r = 0.685, P < 0.01).
      CONCLUSIONS: With hyperoxia exposure, the mRNA expression of specific marker of
      type I alveolar epithelial cell, AQP-5, was decreased while specific marker of
      type II alveolar epithelial cell, SP-B, was increased; and the expression of
      HoxB5 mRNA in lung tissues kept on decreasing. Decreased expression of HoxB5 may
      associate with the disruption of type II-I alveolar epithelial cell
      differentiation and thus may play an important role in inhibition of lung
      development with CLD. The altered Hox gene expression may predispose lung
      pathology.

PMID- 19099819
TI  - [Detection of E2A/PBX1 fusion gene and its clinical significance in childhood
      acute lymphoblastic leukemia].

PMID- 19099818
TI  - [Brain-derived neurotrophic factor and neural stem cells transplantation in
      treatment of hypoxic-ischemic brain injury in rats].
AB  - OBJECTIVE: To investigate the effects of brain-derived neurotrophic factor (BDNF)
      on survival, migration and differentiation of neural stem cells (NSCs)
      transplanted into the brain of newborn rats with hypoxic-ischemic brain damage
      and the recovery of nervous functions. METHODS: The NSCs were separated from
      hippocampus of neonatal Wistar rats within 24 h after birth. Brdu, NSE and GFAP
      were used as markers of differentiation and proliferation of NSCs. The newborn
      rats were subjected to hypoxic-ischemic condition to induce brain damage. Seven
      days later, NSCs transplantation was performed for the animals. The rats were
      divided into normal control group, HIBD group, PBS group, NSCs transplantation
      group, BDNF group and BDNF + NSCs transplantation group randomly. At 4 weeks
      after transplantation the nervous function of rats was observed by Y-maze and
      nerve behavior test. After they were sacrificed, the rat brains were examined by
      immunocytochemistry for Brdu and by immunofluorescence for NSE/Brdu. RESULTS: The
      hippocampus NSCs of newborn rat could be well cultured and they expressed nestin
      and they could differentiate into NSE, GFAP. Most of NSCs survived in cerebral
      ventricle 4 weeks after transplantation in brain through Brdu immunocytochemistry
      and they migrated into regions of brain extensively, especially to the injured
      side of cortex and hippocampus. The number of living NSCs in the injured side of
      cortex and hippocampus of BDNF + NSCs transplantation group increased evidently
      and the percentage of NSCs differentiated into NSE was higher than that in the
      NSCs transplantation group (P < 0.05). The nerve function recovery of the rats in
      BDNF and NSCs treated group was significantly better than that in the other
      groups (P < 0.05). The NSCs group had no prominent changes as compared with the
      model groups (P > 0.05). CONCLUSIONS: NSCs can be isolated from newborn rats
      hippocampus and cultured in vivo. NSCs can survive, migrate and differentiate
      into neurons through cerebral ventricle. BDNF could significantly accelerate
      proliferation and differentiation of NSCs transplanted into the brain of rats
      with HIBD. The nervous function recovery was improved prominently by
      transplantation of NSCs with BDNF application, which may become a potentially
      effective method to treat HIBD.

PMID- 19099820
TI  - [Preliminary investigation on screening for serum protein markers by protein
      microchips technology in childhood acute lymphocytic leukemia].

PMID- 19099821
TI  - [Scurvy in three cases].

PMID- 19099822
TI  - [Report of a case with pure red cell aplasia following recombinant human
      erythropoietin treatment].

PMID- 19099823
TI  - [Systemic lupus erythematosus complicated with respiratory distress in a case].

PMID- 19099824
TI  - [Report of a case with methylmalonic acidemia].

PMID- 19099825
TI  - [Understand scientifically and diagnose and treat attention deficit hyperactivity
      disorder rationally].

PMID- 19099826
TI  - [Association between SNAP-25 gene polymorphism and attention deficit
      hyperactivity disorder].
AB  - OBJECTIVE: To analyse the association between polymorphism in human synaptosomal
      associated protein of 25 000 (SNAP-25) gene and attention deficit hyperactivity
      disorder (ADHD) in Han Chinese children. METHODS: The study samples were
      comprised of 100 integrated ADHD trios (included proband and biological parents)
      and 97 unrelated controls. Association of polymorphism with ADHD and its subtype
      was examined by: (1) comparing cases and controls; (2) using family-based
      association study in transmission disequilibrium test (TDT). RESULTS: Case
      control analysis of short tandem repeat (STR) showed that there was no
      significant difference between the two groups in allele gene frequency and
      genotype frequency (P > 0.05); TDT analysis of the rs363006 SNP and the rs362549
      SNP revealed no association between SNAP-25 polymorphisms and ADHD (P > 0.05).
      But after a stratification by ADHD subtype, the rs362549 SNP A allele showed a
      tendency to preferentially transmitted to ADHD-I subtype (chi(2) = 8.00, P <
      0.01); and the rs362549 SNP G allele had a tendency to preferentially transmitted
      to ADHD-C subtype (chi(2) = 4.122, P < 0.05). CONCLUSIONS: No association was
      found between SNAP-25 polymorphisms and ADHD. There was a possible association
      between rs362549 SNP polymorphism and ADHD subtypes, but the findings require
      replication before drawing a definitive conclusion.

PMID- 19099827
TI  - [Clinical diagnosis and therapy of opsoclonus-myoclonus syndrome].
AB  - OBJECTIVE: Clinical manifestations of opsoclonus-myoclonus syndrome (OMS) in
      children were summarized and analyzed and the clinical features and therapeutic
      approaches to OMS were investigated in order to improve its diagnosis and
      management. METHODS: Clinical information on features and management of 6 cases
      with OMS inpatients being followed up from 2006 to 2007 were collected and
      analyzed. RESULTS: Among the 6 cases, one was male and the other five were
      female. The age at the onset ranged from 12 to 26 months (average 21.0 months).
      Four of them had history of prior infection. The symptoms were opsoclonus,
      myoclonus, ataxia, sleep disturbances and behavioural problems in the 6 cases.
      Urinary DL-3-methoxy-4-hydroxy-acid amygdalin (VMA) was positive in 1 case.
      Abdominal B-mode ultrasound showed a mild hepatomegaly in 4 cases. The EEG showed
      abnormal findings such as slow background activity in 3 cases. Epileptiform
      discharges were found in none of the patients. MRI showed a high signal in medial
      longitudinal fasciculus and tectospinal tract on T2-weighted image in 1 case.
      Computerized tomography found L3-4 arachnoid cysts in 1 case and was normal in
      the others. Adrenocorticotropic hormone (ACTH) was given to all these patients
      and was effective in all during acute stage. In 2 cases the disease relapsed
      during follow-up stage. CONCLUSION: OMS is a rare neurological condition with
      opsoclonus, myoclonus, ataxia, sleep disturbances and behavioral problems, which
      might relapse easily and is associated with adverse neurological outcome. ACTH
      therapy is effective in management of OMS.

PMID- 19099828
TI  - [Peripheral nerve damage and its pathogenesis induced by antiepileptic drugs in
      rats].
AB  - OBJECTIVE: To explore the possibility of peripheral nerve damage induced by
      antiepileptic drugs (AEDs) in different age rats and its pathogenesis. METHODS:
      Adult (2-month-old) and infant (7-day-old) rats were divided into 8 groups (n =
      16 in each) and treated with the following 7 AEDs respectively: phenytoin [PHT,
      62.5 mg/(kgxd)], phenobarbital [PB, 30.0 mg/(kgxd)], sodium valproate [VPA, 312.5
      mg/(kgxd)], clonazepam [CZP, 1.25 mg /(kgxd)], carbamazepine [CBZ, 187.5
      mg/(kgxd)], topiramate [TPM, 40 mg/(kgxd)], oxcarbazepine [OXC, 312.5 mg/(kgxd)],
      remaining one group was used as control. Four weeks later, 8 rats were sacrificed
      randomly from each group and serum, sciatic nerves and spinal cord samples were
      collected. The rest half rats were sacrificed 4 week after AEDs withdrawal.
      Histological observations were performed on the sciatic nerves samples, including
      teased fibers, semi-thin sections and electron microscopy. The activity of total
      antioxidant capacity (T-AOC), superoxide dismutase (SOD) and glutathione
      peroxidase (GSH-PX) in serum and sciatic nerves were detected respectively.
      Expression of apoptosis-related proteins Bcl-2 and Bax was detected by
      immunohistochemistry. Neurons apoptosis in the anterior horns of spinal cord were
      detected by TUNEL. RESULTS: (1) Except for TPM group, various incidence (7.2% -
      20.2%) of teased fibers abnormalities were observed in all the other different
      age groups. PHT group showed the most serious changes followed by PB (adult) or
      VPA (infant), CBZ, CZP and OXC groups. The predominant abnormality of teased
      fibers was demyelination. (2) There was no significant difference in the
      incidence of pathologic changes in teased fibers between adult and infant groups.
      Four weeks after AEDs withdrawal, recovery of pathologic changes in teased fibers
      in infant groups was much better than adult. (3) Significantly increased
      expression of Bax protein and ratio of Bax/Bcl-2 was only found in infant rats
      treated with PB, CNP or VPA compared with control (P < 0.05), the results of
      TUNEL was in accordance with immunohistochemistry. (4) Compared with control, the
      activity of T-AOC and SOD decreased in both infant and adult rats treated with
      PHT, CZP, CBZ and OXC, and the reduction of SOD activity in serum and sciatic
      nerves samples was also found in PB groups. Serum activity of GSH-PX was
      decreased in both age groups treated with PHT, PB, VPA, CZP, CBZ and OXC. The
      reduction of GSH-PX activity in sciatic nerves samples was remarkably in both
      adult and infant rats treated with PHT, PB, CBZ, OXC as well as the infant rats
      treated with CZP. CONCLUSIONS: Six AEDs (PHT, PB, CBZ, VPA, CZP, OXC) showed the
      potential to cause peripheral nerves damage. Demyelination was the predominant
      pathologic change. Both adult and infant rats had the same susceptibility.
      Recovery of pathologic changes in teased fibers in both age groups was slow, but
      infant rats were prone to revive more quickly. There was no significant
      correlation between spinal cord neuron apoptosis and peripheral nerves damages in
      rats treated with AEDs. Breakdown of oxidation-antioxidation balance was closely
      related to development of peripheral nerves damages caused by most AEDs.

PMID- 19099829
TI  - [Effect of eyes closure, eyes closed and photic stimulation on the epileptiform
      discharges in children with epilepsies].
AB  - OBJECTIVE: To investigate the effect of eyes closure and closed on the
      epileptiform discharges, and the relationship between eyes closure or closed
      sensitivity and photosensitivity. METHODS: During video-EEG monitoring, open
      close eyes tests and intermittent photic stimulation (IPS) under different eyes
      conditions were carried out in epilepsy patients. The eyes conditions were
      divided into eyes opened, eyes closure (the period immediately after closing of
      the eyes and only lasts for less than 3 s), and eyes closed (the period lasting
      for more than 3 s and persisting as long as the eyes remain closed). From 135
      patients, 13 cases whose EEG showed eyes closure or closed sensitivity had been
      selected out for our study. The clinical, eyes closure or closed sensitivity and
      the relationship between eyes closure or closed sensitivity and photosensitivity
      were analyzed. RESULTS: Of the 13 patients, 8 were female, and 5 were male. The
      age ranged from 6 years to 17 years (median 11 years). The age at onset of
      epilepsy ranged from 1.5 years to 14.5 years (median 9 years). Epileptiform
      discharges could be provoked by eyes closure in 10 of 13 patients, associated
      with photosensitivity in 8 patients. Of the 8 patients, 6 cases showed
      photosensitivity under eyes closure and only 4 cases showed photosensitivity
      under eyes closed. Eyes closed sensitivity had been seen in 3 patients, with
      photosensitivity in 2 patients. Evoked EEG patterns and discharges regions by
      eyes closure and eyes closed conditions had not obvious differential and might be
      strongly related to the types of epilepsies. The intensity and frequencies of
      photosensitivity under different eyes conditions were different. After valproate
      acid treatment, the eyes closure or closed sensitivity and photosensitivity
      improved in 4 cases, with improvement of photosensitivity prior to eyes
      conditions sensitivity. CONCLUSIONS: Eyes closure and eyes closed could induce
      EEG paroxysms, which involved in some types of epileptic syndromes and appeared
      common in female patients. Eyes closure or closed sensitivity might coexist or be
      disassociated with photosensitivity. Testing eyes closure, eyes closed and IPS
      during EEG monitoring would contribute to finding the EEG discharges, further
      help to diagnose epilepsies and epileptic syndromes and guide treatment.

PMID- 19099830
TI  - [Roles and signal pathways of adrenomedullin and adrenotensin in pulmonary
      remodeling due to left to right shunt in rats].
AB  - OBJECTIVES: The effect of vascular active peptides on the development of
      pulmonary remodeling and pulmonary hypertension due to left to right shunt
      congenital heart diseases is the focus of today's studies. The present study was
      conducted to investigate the roles of adrenomedullin (ADM) and adrenotensin (ADT)
      in pulmonary remodeling due to left to right shunt in rat lungs. METHODS: Twenty
      one male Wistar rats were divided into two groups randomly. A right common
      carotid artery to external jugular vein shunt operation was performed on
      experimental rats (n = 9) to establish a left to right shunt animal model.
      Meanwhile, the common carotid artery and external jugular vein of the control
      group rats (n = 12) were just isolated without connection. Twelve weeks later,
      the mean pulmonary artery pressure (mPAP), the right ventricle to left ventricle
      plus septum ratio [weight, RV/(LV + SP)], the percentage of media wall thickness
      (MT%) were calculated. The distributions and relative protein contents of ADM and
      ADT in lungs were measured by immunohistochemical staining and Western blotting
      analysis. The relative gene expression for ADM, ADT, p46-p54 stress-actived
      protein kinase (SAPK) and p44 extracellular signal-regulated protein kinase 1
      (ERK(1)) were investigated by RT-PCR. RESULTS: The muscular and the tunica
      intimae layer of pulmonary artery were thicker in experiment group rats than
      those of control group, and the mPAP increased significantly in shunt group
      [(27.10 +/- 6.67) mm Hg (1 mm Hg = 0.133 kPa)] compared with that in control
      group [(14.32 +/- 3.14) mm Hg] (t = 5.5507, P < 0.001). The ratios of RV/(LV +
      SP) and MT% increased significantly in experimental group in contrast to the
      control group (P < 0.001). ADM and ADT positive granules distributed mainly over
      vascular smooth muscle cells, and Western blotting and integrated optical density
      analysis showed that the content of ADM increased in shunt group rats (P <
      0.001), however, ADT content decreased (P < 0.001). The mRNA expression of ADM,
      SAPK and ERK(1) up-regulated in experiment group compared with the control group
      (P < 0.01, and P < 0.001 respectively), however, the ADT mRNA expression
      decreased in experimental rats in contrast to the control group (P < 0.001).
      CONCLUSIONS: The phenomenon of intramolecular regulation of ADM and ADT, which
      both derived from proadrenomedullin, existed in the development of pulmonary
      remodeling and pulmonary hypertension due to left to right shunt. The mitogen
      activated protein kinases (MAPKs) signal transduction pathway has been activated
      in the formation of left to right shunt pulmonary remodeling and pulmonary
      hypertension, and ADM may slow down the occurrence of pulmonary hypertension
      through cutting off MAPKs signaling pathway.

PMID- 19099831
TI  - [Mutations in NPHS2 in familial steroid-resistant nephrotic syndrome in Southern
      Chinese Han ethnic group].
AB  - OBJECTIVE: Mutations in NPHS2 mapped to 1q25-q31 and encoding podocin, which is
      exclusively expressed in glomerular podocytes, are responsible for autosomal
      recessive familial steroid-resistant nephrotic syndrome (SRNS) with minor
      glomerular abnormalities or focal segmental glomerulosclerosis. Different groups
      from European and North American countries have screened NPHS2 mutations in
      familial SRNS with recessive inheritance, documenting a mutation detection rate
      of 45% - 55% in families. This study aimed to examine mutations in the NPHS2 gene
      in Southern Chinese Han ethnic group patients with familial SRNS. METHODS:
      Genomic DNA from 3 probands from Southern Chinese Han families with autosomal
      recessive SRNS, and their siblings and parents was isolated and analyzed for all
      eight exons, exon-intron boundaries and promoter of NPHS2 using the polymerase
      chain reaction and direct sequencing. RESULTS: No mutation of NPHS2 in all eight
      exons and exon-intron boundaries was identified in the 3 probands. However, a
      polymorphism of 954T > C in exon 8 was detected in all the 3 probands and some
      controls, and 5 variants of NPHS2 promoter, -1709G > A, -1000A > T, -670C > T, 
      116C > T and -51G > T, were identified in some patients and controls, indicating
      that these variants are polymorphisms. One heterozygous variant of NPHS2
      promoter, -1715A > G, was also identified in one proband and her mother whose
      urinalyses were normal, whereas it was not found in any of the 50 controls. There
      was no significant difference in the allelic frequencies of -1709G > A, -1000A >
      T, -670C > T, -116C > T and -51G > T polymorphisms between the patients and
      controls. CONCLUSION: NPHS2 mutations are not a major cause of familial steroid
      resistant nephrotic syndrome in Southern Chinese Han ethnic group included in the
      study.

PMID- 19099832
TI  - [Adenosine deaminase deficiency associated severe combined immunodeficiency with
      disseminated varicella infection after vaccination: a case report].
AB  - OBJECTIVE: To enhance the knowledge of adenosine deaminase (ADA) deficiency
      associated severe combined immunodeficiency (SCID) with disseminated varicella
      infection after vaccination. METHODS: With case report and review of literature,
      the background knowledge, clinical and laboratory findings, diagnosis and
      treatment of ADA-deficient SCID were discussed. RESULTS: The patient had the
      condition with failure to thrive. The main complaint was more than three weeks of
      fever and rash. He had received the live attenuated Oka strain varicella
      vaccination approximately two weeks before the onset of rash. Varicella infection
      was confirmed with direct immunofluorescence assay. The patient had mild
      leukopenia, with 3% lymphocytes. The initial immunologic workup included
      decreased IgG, IgM and IgA, abnormal expanded lymphocyte enumeration which
      confirmed the reduction of CD3, CD4, CD8, CD19 and CD56. Enzyme testing for ADA
      activity showed remarkably low level in the hemolysate, as well as increased
      levels of deoxyadenosine nucleotides. CONCLUSION: ADA-deficient SCID has some
      characteristic clinical and laboratory findings. Management options for ADA
      deficient SCID include hematopoietic stem cell transplantation, enzyme
      replacement therapy and gene therapy. Immunodeficiency should be considered in
      children with severe failure-to-thrive. Live vaccine administration should be
      avoided in patients with immunodeficiency.

PMID- 19099833
TI  - [Primary immunodeficiency complicated with Bacillus Calmette-Guerin infection:
      identification and clinical phenotype of a case of novel interleukin-12Rbeta1
      gene mutation].
AB  - OBJECTIVE: Interleukin-12 receptor beta1 (IL-12 Rbeta1) deficiency is a rare
      primary immunodeficiency (PID) characterized by selective susceptibility to
      weakly virulent organisms, including Mycobacterium bovis, BCG, non-tuberculous
      environmental mycobacteria and non-typhoidal salmonellosis. The present study was
      conducted to identify the mutation type and to analyze clinical phenotype.
      METHODS: Based on the typical clinical manifestations and immunologic tests in
      this case, a varieties of PIDs were excluded and IL-12Rbeta1 deficiency was
      suspected. IL-12Rbeta1 chain expressed on Epstein-Barr virus-transformed
      lymphoblastoid B cell lines were detected by flow cytometric assay. The IL
      12Rbeta1 gene sequences of the patient and her parents were analyzed by PCR
      directed sequencing. The IL-12Rbeta1 gene sequences of the patient's younger
      brother also had been analyzed prenatally and after birth. RESULTS: After
      inoculating BCG, the patient suffered from multiple BCG infectious lymphadenitis.
      There was no detectable IL-12Rbeta1 on the Epstein-Barr virus-transformed
      lymphoblastoid B cell lines from the patient, while only mild expression on the
      cell line from her mother. Sequencing analysis by using sense and antisense
      primers separately, a novel IL-12Rbeta1 gene mutation was found in the patient
      which was homozygous single nucleotide substitution, a nonsense mutation with
      nucleotide substitution of C to T at position 853 (853C-->T) in exon 9 leading
      the glutamate at position 285 to the stop codon mutation (Q285X). The parents
      were carriers of the mutated IL-12Rbeta1 gene. But her younger brother has normal
      IL-12Rbeta1 gene. CONCLUSION: The novel IL-12Rbeta1 gene mutation is responsible
      for BCG infection in this case and genetic analysis is useful in carrier
      detection and prenatal diagnosis is feasible when the mother had a baby with
      identified IL-12Rbeta1 gene mutation before.

PMID- 19099834
TI  - [Eukaryotic expression and determination of ZCH-7-2F9 single chain antibody
      against human CD14].
AB  - OBJECTIVE: Acute monocytic leukemia (AML)-M5 is the common type of acute myeloid
      leukemias in children. Studies have shown that there are abundant
      lipopolysaccharide (LPS) receptor (designated as CD14) molecules on the cell
      membrane of M5 cells and they play an important role in the diagnosis of M5,
      since they can be recognized and bound by mouse-anti-human CD14 monoclonal
      antibody (McAb). However, mouse-originated antibodies are largely not suitable
      for clinical application due to the severe side effects, thus "humanized
      antibody" is desired. As the first step for developing humanized antibody, the
      construction and expression of single chain antibody (scFv) with functional
      protein are necessary. The present study aimed to express ZCH-7-2F9 ScFv
      (scFv(2F9)) in eukaryotic cells and obtain the scFv(2F9) protein with a high
      biological activity. METHODS: Four primers were synthesized to construct the
      eukaryotic expressional vector, which included SfiI and EcoRI enzyme cleaving
      site, 6 x His and stop code TGA sequences. scFv(2F9) gene was amplified through
      splicing by overlap extension (SOE) using the high fidelity Taq polymerase.
      Positive recombinants (pSectag2A/scFv(2F9)) were identified through enzyme
      cleaving and sequenced before expression and were transformed into Chinese
      hamster ovary (CHO) cells for expression. Western-Blot and flow cytometry (FCM)
      were carried out to determine the relative molecular mass (Mr) and binding
      activity of scFv(2F9). RESULTS: The cloned scFv(2F9) gene was identified to be
      functional by sequencing and expressing. The interested protein could be detected
      in the culture supernatant of transformed CHO cells with an Mr of 31 000. The
      blocking test showed that the positive cell percentages, the mean fluorescence
      intensity (MFI) and the peak of channel (peak Ch) were reduced by 90.02%, 63.30%
      and 63.38%, respectively after blocking with scFv(2F9), while those were 4.55%,
      10.09% and 5.02% after blockage using the supernatant from the CHO cells
      transfected with blanked vector pSectag2A. CONCLUSIONS: The scFv(2F9) against
      human CD14 antigen was successfully expressed in eukaryotic cells and showed a
      high biological activity, which may be useful for the further studies on its
      humanized antibodies.

PMID- 19099835
TI  - [Determination of the serum mannose binding lectin levels in 738 Han ethnic group
      children].
AB  - OBJECTIVE: To investigate the distribution of serum mannose binding lectin (MBL)
      levels in Han ethnic group children. METHODS: The concentrations of MBL in serum
      were measured by ELISA in 268 umbilical cord blood specimens from Chongqing,
      Wuhan and Urumqi as well as in serum of 470 normal children aged from 0 to 6
      years and 87 adults in Chongqing. RESULTS: The distribution of serum MBL levels
      in children (28 days to 6 years) was abnormal but there was no significant
      difference in MBL serum levels in subjects of different ages and genders. The
      median concentration of MBL in serum was significantly lower in newborns (median:
      1597 microg/L, range: 884 - 1825 microg/L), cord blood group (median: 1462
      microg/L, range: 0 - 4604 microg/L) than in other groups (children group median:
      2536 microg/L, range 0 - 7860 microg/L; adult group median: 2920 microg/L, range
      98 - 6495 microg/L). While among the other sub-groups aged from 28 days-6 years
      (28 day group median 2299 microg/L, range 214 - 4195 microg/L; 6 months-group
      median 2622 microg/L, range 5 - 4637 microg/L; 2 years-6 years group 2585
      microg/L, range 198 - 7860 microg/L), there was no statistically significant
      difference. The median serum MBL level in normal children aged from 28 days to 6
      years was 2563 microg/L and the P(2.5)-P(97.5) was 171 - 5079 microg/L.
      CONCLUSIONS: The distribution of serum MBL levels in children (28 days to 6
      years) was abnormal type but there was no statistically significant difference
      among different age and sex groups. The reference value of P(2.5)-P(97.5) in
      children (28 days-6 years) was 171 - 5079 microg/L.

PMID- 19099836
TI  - [Application of fluorescent real-time polymerase chain reaction in analyzing the
      epidemic of influenza among children in Guangzhou area in 2006].
AB  - OBJECTIVE: To investigate the prevalence of influenza virus infections in
      children in 2006 using the real-time PCR method. METHODS: (1) Consulting the most
      conserved sequence NP gene of influenza virus, after comparing with the NP gene
      sequences of influenza virus in GenBank, one pair of specific primers and one
      TaqMan probe were designed for each subtype of influenza virus by the software
      Primer Express. The sensitivity of influenza was evaluated by testing known
      positive samples which had been two-fold diluted. The specificity of real-time
      PCR for influenza virus detection was assessed by cross testing 60 isolates of
      influenza A, 16 isolates of influenza B, and by testing a variety of other
      respiratory viruses positive samples; (2) 281 nasopharyngeal aspirate samples
      were detected by real-time PCR and virus isolation; (3) the 12 301 specimens from
      the patients of Guangzhou Children's Hospital were tested by using the real-time
      PCR method. Furthermore, the real-time PCR reagent was evaluated by comparing
      with the result of virus isolation. RESULTS: (1) The sensitivity of real-time PCR
      developed in this study for influenza A detection was 1:2(22) and for influenza B
      was 1:2(20) in two-fold serially diluted way. (2) No positive results were found
      in cross testing of other viruses positive specimens. (3) Influenza virus was
      detected from 1687 cases (13.71%) out of the 12 301 cases, including 773 cases
      (45.8%) positive for subtype A and 914 cases (54.2%) positive for subtype B; 455
      out of 525 (86.7%) of influenza B positive specimens and 70 out of 525 (13.3%) of
      influenza A (H1N1) positive specimens were from patients seen during January to
      April; 419 out of 1118 (37.5%) specimens positive for influenza B and 699 out of
      1118 (62.5%) specimens positive for influenza A (H1N1) were from patients seen
      from May to August. Influenza virus could be identified from 1380 samples by the
      methods of virus isolation, accounting for 81.80% of the 1687 positive samples
      detected by real-time PCR. All the influenza virus subtype A was H1N1.
      CONCLUSION: The real-time PCR method developed in this study was sensitive and
      specific for detecting influenza A and B in clinical specimens. During 2006,
      influenza A and influenza B co-circulated. The predominant virus was influenza B
      from January to April, peaking in April. Influenza A (H1N1) prevailed from May to
      August, with the peak in June.

PMID- 19099838
TI  - [Effects of gene regulation by simvastatin on proliferation and phenotype of the
      pulmonary vascular smooth muscle cells].

PMID- 19099837
TI  - [Clinical characteristics of primary ciliary dyskinesia in children].
AB  - OBJECTIVE: Although primary ciliary dyskinesia (PCD) is a group of inherited
      diseases, accurate diagnosis and appropriate clinical care to prevent and treat
      the complications could maintain patients' quality of life and normal life span.
      The diagnosis of PCD may often be delayed because it is frequently misdiagnosed
      as bronchitis, sinusitis and otitis. This study aimed to analyze and summarize
      the clinical features of PCD and explore diagnostic and differential diagnostic
      procedures in children. METHODS: Patients were all chosen from the inpatient
      department of Beijing Children's Hospital, Capital Medical University between
      1990 - 2006. The tunica mucosa bronchiorum and/or nasal mucous membrane were
      gained through bronchoscope in children suspected to have PCD. The ciliary
      ultrastructures were analyzed through the electron microscope. The clinical
      features and procedures of the diagnosis and differential diagnosis in children
      with PCD were analyzed. RESULTS: There were totally 26 children diagnosed as PCD
      with 10 (38.5%) Kartagener syndrome. All Kartagener syndrome children had mirror
      image dextrocardia with normal cardiac structure and situs inversus viscerum. The
      bronchoscopy performed in eight of 10 Kartagener syndrome children showed
      bronchus transposition. Twenty-six children came from twenty-five families.
      Although the siblings of four probands also had the symptoms of chronic cough
      with sputum, running nose and recurrent respiratory infections, only a boy and
      his sister were diagnosed as Kartagener syndrome simultaneously. Their parents
      and the other family members were healthy. Of the 26 patients, 11 were boys and
      15 were girls. The median age at diagnosis was 8.7 years. The age of onset was
      between the second day after delivery and fifteen years old, median age was 3
      years. The course of disease before diagnosis was eleven days to twelve years
      (median 3.5 years). All the children had the symptom of cough, 24 of which had
      productive cough. Seven cases were found to have clubbing fingers. Dynein arm
      defect was found in 10 children, 6 of them had total absence of dynein arms and 4
      had decreased dynein arm numbers. Microtube derangements were found in 8
      children. One Kartagener syndrome child had a normal cilia structure.
      Bronchiectasis, consolidation and increased lung markings were found in 8, 6 and
      7 patients separately on the radiographic study. Twenty patients had sinusitis.
      Nine of sixteen children had decreased PEF, FEV1 and/or FEF 25 - 75 on the
      pulmonary function test. Fifteen culture samples obtained from 6 children's
      sputum and/or bronchoalveolar lavage fluid were positive for 8 strains of
      Pseudomonas aeruginosa, 5 strains of Streptococcus pneumoniae and 2 strains of
      Candida albicans. In 1 subject more than one organism were found in the same
      sample. Hearing lost and gastroesophageal reflux were detected in 3 of 4 and 3 of
      5 examined children respectively. CONCLUSIONS: The onset of PCD can occur from
      neonate to adolescence and usually has a chronic course. The common symptom of
      pediatric PCD was productive cough and significant growth retardation. The most
      common ultrastructural abnormalities associated with PCD were the total absence
      of dynein arms, decreased dynein arm numbers and microtube derangement. Some
      patients have normal ciliary structures. Bronchiectasis, consolidation and
      sinusitis were usually seen on the radiography. Pseudomonas aeruginosa and
      Streptococcus pneumoniae were the two common bacterial organisms obtained from
      sputum and/or bronchoalveolar lavage fluid of PCD children. Some patients have
      mixed infections. PCD children have high percentages of hearing lost and
      gastroesophageal reflux.

PMID- 19099839
TI  - [Matrine's inhibitory effect on apoptosis of cardiomyocytes induced by coxsackie
      virus B(3) and on calcium overload].

PMID- 19099840
TI  - [Expressions and significances of hepatocyte growth factor and its receptor c-Met
      in renal tissues of children with primary nephrotic syndrome].

PMID- 19099841
TI  - [Electroencephalogram characteristics of Rett syndrome].

PMID- 19099842
TI  - [Clinical features and management of multiple pituitary hormone deficiencies with
      adrenocorticotropic hormone deficiency in children].

PMID- 19099843
TI  - [Retrospective analysis on twenty Chinese cases of cystic fibrosis].

PMID- 19099844
TI  - [Disseminated Penicillium marneffei infection in infant: a case report].

PMID- 19099845
TI  - [Report of a case with hyper-IgE syndrome].

PMID- 19099846
TI  - [The question on treatment of sick children with hand, foot and month disease
      with corticosteroids and the answer].

PMID- 19099847
TI  - [Diagnosis and therapy of hypoxic-ischemic encephalopathy in China: current
      challenges and suggestions].

PMID- 19099848
TI  - [Effects of hypoxia-ischemia on different neural cells in subventricular zone of
      human fetus].
AB  - OBJECTIVE: To investigate the effects of hypoxia-ischemia (HI) on different
      neural cells and their survival in subventricular zone (SVZ) of human fetus in
      mid trimester of pregnancy and thus to explore the pathogenesis of hypoxic
      ischemic brain damage on the cellular level. METHODS: Acutely dissociated SVZ
      cells, prepared from five fetuses of human embryos aborted voluntarily at 17 to
      22 weeks of gestational age, were cultured for a short time separately under HI
      (HI group) and normal condition (control group). HI injury was simulated by
      oxygen/glucose deprivation (OGD) and the dead cells were counted by staining with
      Trypan blue. The injury was evaluated by the survival rate before culturing.
      After culturing, all of the neural cells of SVZ, including neural stem cells
      (NSCs), neurons, astrocytes, oligodendrocyte progenitors and microglia cells were
      recognized separately by their special marker nestin, microtubule associated
      proteins 2 (MAP2), glial fibrillary acidic protein (GFAP), platelet derived
      growth factor receptor alpha (PDGFRalpha) and ricinus communis agglutinin
      (RCA120) with immunofluorescence cytochemistry. At the same time, all cell nuclei
      were stained with bisbenzimide. The percentages of SVZ cells were calculated and
      compared between HI and control groups. RESULTS: The survival rate of HI SVZ
      cells, (63.41 +/- 0.06) percent, was much lower than that of control (98.9 +/-
      0.01) percent (P < 0.001). The result indicated that SVZ cells were damaged
      obviously by HI. After culturing shortly the highest proportion of cells in HI
      group was astrocytes (56.48 +/- 0.03) percent, followed by NSCs (22.47 +/- 0.03)
      percent, and the lowest was oligodendrocyte progenitors. But in control group,
      the neurons accounted for (48.81 +/- 0.03) percent and astrocytes (32.31 +/-
      0.03) percent, while the lowest was microglia cells. CONCLUSIONS: There were
      NSCs, neurons, astrocytes, oligodendrocyte progenitors and microglial cells in
      SVZ of mid trimester of pregnancy. They were sensitive to HI and their survival
      rates were different: the NSCs and astrocytes showed higher survival rate than
      neurons and oligodendrocyte progenitors.

PMID- 19099849
TI  - [Effects of bone marrow mesenchymal stem cells on learning and memory functional
      recovery in neonatal rats with hypoxic-ischemic brain damage].
AB  - OBJECTIVE: Neonatal hypoxic-ischemic brain damage (HIBD) causes acute death and
      chronic nervous system sequelae in newborn infants and children. Whereas there
      have been no specific treatment towards it up to now. Studies have shown that
      bone marrow mesenchymal stem cells (MSCs) have the therapeutic potential in many
      nervous system diseases and the authors previously found that retinoid acid (RA),
      which plays an important role in brain development, could enhance the neural
      differentiation of rat MSCs (rMSCs) in vitro. This study aimed to examine effects
      of rMSCs and RA-preinduced rMSC on learning and memory functional recovery after
      HIBD in neonatal rats in order to explore a new treatment strategy for clinical
      application, and explore the mechanism of action of rMSCs. METHODS: Rat MSCs were
      isolated and purified from the whole bone marrow of juvenile Wistar rats by
      removing the non-adherent cells in primary and passage cultures. Neonatal hypoxic
      ischemic brain damage rat models were built according to the methods described by
      Rice: the right carotid artery of 7-day-postnatal Wistar rats was ligated under
      anesthesia, and then the rats were exposed to 8% - 9% O2 in a container. At 5
      days after hypoxia-ischemia, the HIBD neonatal rats were randomly divided into 3
      groups and respectively transplanted with saline, BrdU marked rMSCs (1 - 2 x
      10(5)) or RA-preinduced rMSCs (1 - 2 x 10(5)) into their lateral cerebral
      ventricle. Immunohistochemistry for nestin, neuron-specific enolase (NSE),
      neurofilament protein-heavy chain (NF-H) and glial fibrillary acidic protein
      (GFAP) were used to identify cells derived from rMSCs at 14 days and 42 days
      after transplantation. Shuttle box test was performed to evaluate the condition
      of learning and memory functional recovery when animals were 7 weeks old.
      Neurotrophin and receptors cDNA microarray were also employed at 14 days after
      transplantation to investigate the underlying action mechanisms of rMSCs
      treatment. Real-time PCR was used to confirm some of the remarkably changed
      genes. RESULTS: (1) The neonatal rat model of HIBD was successfully established.
      (2) Immunohistochemistry showed rMSCs-derived cells survived, migrated into the
      hypoxic-ischemic brain tissue and a few of them expressed protein characteristic
      of neurons and astrocytes (NF-H and GFAP) in RA-preinduced group 14 days and 42
      days after transplantation, while no positive expression of nestin and NSE were
      detected. (3) The shuttle box test showed that the average learning times in rats
      transplanted with saline, rMSC and RA-preinduced rMSCs were (94.10 +/- 38.18),
      (74.60 +/- 29.21) and (47.90 +/- 21.13), respectively. The difference between the
      former two was not significant (P > 0.05), while the latter one exhibited
      significant improvement (P < 0.05). (4) The cDNA microarray analysis showed that
      compared with normal control group, IL-6, Fas and BDNF genes of the saline
      control group significantly up-regulated (the ratios of the three genes were
      11.4, 2.4 and 6.6 respectively). Compared with saline group, the three genes in
      rMSC group were down-regulated (the ratios were all 0.1), while the levels of IL
      6 and Fas genes (the ratios were 0.3 and 0.4 respectively) in RA-preinduced rMSCs
      group were higher than rMSCs group after down-regulating, but the level of BDNF
      remained at the saline group level. Real-time PCR analysis suggested that the
      results of IL-6 and Fas genes were at equal level with microarray results on the
      whole, while the level of BDNF gene in RA-preinduced rMSC group was significantly
      down-regulated (with ratio of 0.34), but higher than rMSCs group (the ratio was
      0.25) as well. CONCLUSION: Transplantation of rMSC and RA-preinduced rMSCs into
      lateral cerebral ventricle can improve learning and memory functional recovery
      after HIBD in neonatal rats, especially RA-preinduced rMSCs. Regulating the
      levels of IL-6, Fas and BDNF in the brain to maintain at reasonable levels may be
      the mechanism.

PMID- 19099850
TI  - [Clinical characteristics and outcomes of respiratory distress syndrome in term
      and late-preterm neonates].
AB  - OBJECTIVE: Respiratory distress syndrome (RDS) is a frequently seen acute
      respiratory disorder in the newborn infants. Since the original description of
      deficiency of the pulmonary surfactant in premature neonates by Avery in 1959,
      RDS has most commonly been attributed to developmental immaturity of surfactant
      production. But in clinical practice it has been found that there was RDS in term
      and late-term neonates. Many of them were recognized as transient tachypnea at
      the beginning, they were diagnosed as RDS until respiratory distress and the
      typical radiological signs were demonstrated. The purpose of this study was to
      investigate the clinical characteristics of RDS of term and late-term neonates.
      METHODS: All neonates admitted to the neonatal intensive care unit of the
      Children's Hospital, Zhejiang University School of Medicine between May, 2005 and
      May, 2007 on the basis of RDS were analyzed. RDS was diagnosed when respiratory
      distress and the typical radiological signs were documented. Patients were
      grouped into preterm group (Group 1, gestational age < 35 w, n = 103) and term
      and late-term group (Group 2, gestational age > or = 35 w, n = 74). RESULTS: In
      Group 1, 76 preterm infants were male, the mean gestational age was 31.1 w, the
      mean Apgar score at 1 min was 7.6, the mean birth weight was 1702 g, 56 cases
      were vaginally delivered and 47 were delivered through Cesarean section. Only one
      was delivered via elective Cesarean section before onset of labor. A total of 88
      patients needed mechanical ventilation (MV), the time for beginning MV was 8.7 h
      (1 - 72 h), and lasted for 4.3 d (0.5 - 29 d). The oxygenation index (OI) was
      11.9 (10.00 - 52.63) and PaO2/PAO2 was 0.29 (0.03 - 0.98). Four patients had an
      OI > 40. A total of 28 patients were treated with pulmonary surfactant (PS), and
      11 of the 28 underwent MV, the OI before and 2 h, 8 - 12 h and 20 - 24 h after
      using PS were 10.5, 5.4, 3.4, and 4.3, respectively (P < 0.01). A total of 33
      patients in Group 1 had intracranial hemorrhage, 4 patients had pneumothorax, 4
      patients had persistent pulmonary hypertension of the newborn (PPHN) and 15
      patients had ventilator associated pneumonia (VAP). In Group 2, 54 infants were
      male, the mean gestational age was 37 w, the mean Apgar score at 1 min was 8.5,
      the mean birth weight was 2789 g, 8 cases were vaginally delivered, 66 were
      delivered through Cesarean section and 59 were delivered via elective Cesarean
      section before onset of labor. A total of 63 patients needed MV, the time for
      beginning MV was 27.8 h (1 - 72 h, compared to Group 1, P < 0.01), and lasted for
      3.7 d (0.5 - 13.5 d). The OI was 19.70 (10.00 - 56.67, compared to Group 1, P <
      0.01) and PaO2/PAO2 was 0.16 (0.017 - 0.470, compared to Group 1, P < 0.01).
      Seven patients had an OI > 40. A total of 8 patients were treated with PS and 7
      of them had MV, the OI before and 2 h, 8 - 12 h and 20 - 24 h after using PS were
      11.2, 7.6, 7.5, and 7.6 (the last two compared to group 1, P < 0.01,
      respectively). A total of 16 patients had pneumothorax, 10 patients had
      intracranial hemorrhage, 16 patients had PPHN and 7 patients had VAP. CONCLUSION:
      Most of the term and late-term neonates who developed RDS were delivered through
      cesarean section before onset of labor. They underwent MV later. The oxygenation
      was worse than RDS in preterm infants. PS did not have the same effect as seen in
      preterm infants. They had more pneumothorax and PPHN.

PMID- 19099851
TI  - [Influence of congenital asymptomatic cytomegalovirus infection on development of
      infants].
AB  - OBJECTIVE: Human cytomegalovirus (HCMV) is a ubiquitous human-specific DNA virus
      and is the main cause of congenital virus infection worldwide. Although 90% of
      the congenitally infected infants are clinically asymptomatic at birth, evidences
      show that these infants are at risk for audiologic, neurologic, and developmental
      sequelae. The aim of this study was to evaluate the outcome of children with
      asymptomatic congenital human cytomegalovirus infection identified from a cohort
      of newborn infants screened for congenital HCMV infection compared with matched
      uninfected control subjects. METHODS: Between July 2003 and July 2005, eligible
      hospitalized infants were recruited into the cohort. Serum was collected within
      two weeks of birth and transported to the laboratory within 24 hours, and stored
      at -20 degrees C. Then Real-time fluorescent quantitative polymerase chain
      reaction (FQ-PCR) for the presence of HCMV DNA was used as a screening tool for
      the detection of congenital cytomegalovirus infection. Asymptomatic congenital
      HCMV infection (ACCMV) was defined as detection of HCMV during the first 2 weeks
      of life in the absence of any abnormal signs, symptoms, or laboratory findings.
      The study enrolled 41 siblings with asymptomatic congenital HCMV infection and 21
      children whose neonatal screening for congenital HCMV infection showed negative
      results. Then they were followed up prospectively for the first years of life. A
      pediatric assessment, including neonatal behavioral neurological assessment
      (NBNA) was performed at neonatal period by a qualified pediatrician, at which
      time the CMV status of the infants was not yet known. At one year of age other
      standardised clinical evaluations were performed by the pediatrician. The Bayley
      scale of infant development were used to determine the intellectual and
      neurological development deficits, and the age-adequate neurological examinations
      based on the criteria by Amiel-Tison to evaluate the general movements for
      neurological development. Hearing screening were completed for all children to
      determine their hearing status. Auditory brain-stem response (ABR) and distortion
      product otoacoustic emission (DPOAE) have been used to accurately diagnose
      moderate to profound congenital sensorineural hearing loss. RESULT: There was no
      significant difference between the mean NBNA score of HCMV group (38.8 +/- 2.75)
      and the control group (38.5 +/- 2.29) (t = 0.98, P > 0.05). Significant
      difference was found between the occurrence of hearing loss in infants born with
      asymptomatic congenital HCMV infection compared with the control group.
      Audiologic abnormalities (sensorineural hearing loss, SNHL) were present in 5 of
      23 congenitally infected children, however, no hearing abnormalities were
      detected in uninfected children (chi2 = 6.94, P < 0.01). The mean Bayley score of
      HCMV group (MDI 106.86 +/- 10.24 and PDI 108.45 +/- 18.25) and the control group
      (MDI 107.49 +/- 19.31 and PDI 107.19 +/- 10.98) did not differ significantly (t =
      0.33, P > 0.05, t = 0.35, P > 0.05). Otherwise, there was no significant
      difference in 52 Amiel-Tison neurological scale between the two groups.
      CONCLUSION: These data suggest that asymptomatic congenital cytomegalovirus
      infection may be associated with a broad range of audiologic differences in early
      infancy. Continued monitoring of their hearing status in the first years of life
      is necessary in these children because further progression of hearing loss is
      possible. However, asymptomatic congenital HCMV infection is not associated with
      abnormalities in growth, or neurodevelopmental deficits.

PMID- 19099852
TI  - [Pneumocephalus caused by neonatal Enterobacter cloacae infection in a case].
AB  - OBJECTIVE: Gas-containing encephalo-meningitis is very rare. There have only been
      a few cases reported in the literature. The majority of neonatal cases reported
      in literature died. We report a case of a 5-day-old neonate who developed diffuse
      pneumocephalus from Enterobacter cloacae septicemia and intracranial infection.
      METHOD: This neonate was initially treated with penicillin and mezlocillin. He
      also received phototherapy, intravenous infusion, correction of acidosis and
      other supportive therapy. Complete blood count, C-Reactive protein, cranial CT
      scan, blood culture, cerebrospinal fluid culture and biochemistry were tested
      repeatedly. RESULTS: This neonate's condition deteriorated after admission. He
      developed respiratory distress, increased muscle tone and decreased level of
      consciousness. His WBC and C-reactive protein were elevated, while blood gas,
      electrolytes, liver enzymes and renal function were within normal range
      initially. Cranial CT scan was done which demonstrated diffuse pneumocephalus. He
      was transferred to a higher level hospital for further management at the request
      of the family. Blood culture done in our hospital subsequently showed growth of
      Enterobacter cloacae. The infant developed seizures and further deterioration in
      level of consciousness after transfer. Antibiotics were switched to penicillin
      and ceftizoxime. Cranial CT scan repeated 2 days after transfer showed
      hydrocephalus and some resolution of pneumocephalus. Cerebrospinal fluid (CSF)
      was aspirated from the lateral ventricles two weeks after admission. CSF culture
      also showed growth of Enterobacter cloacae. Antibiotic was switched to imipenem
      according to antibiotic sensitivity. His general condition was improved. Blood
      and CSF cultures were negative 1 month after admission. His head circumference at
      discharge was 34.6 cm. Repeat cranial CT scan at 4 month of age demonstrated
      severe hydrocephalus, diffuse leukomalacia and calcification. This infant
      suffered significant neurodevelopmental deficit. Muscle tone was diffusely
      increased. Head circumference at 9 month of age was 48.4 cm. CONCLUSION: This
      case suggests the importance of Enterobacter cloacae infection in the newborns.
      Our analysis of 34 cases of Enterobacter cloacae infection showed that 93.75% -
      100% were sensitive to quinolones, 94.12% were sensitive to imipenem, 73.33% were
      sensitive to gentamicin, 50% were sensitive to piperacillin-tazobactam.
      Enterobacter cloacae is generally not sensitive to penicillin, first and second
      generation cephalosporins (0 - 21.4%). Enterobacter cloacae septicemia and
      intracranial infection in neonates have a high mortality rate and can result in
      severe neurodevelopmental deficit in survivors.

PMID- 19099854
TI  - [Discussion on the use of antibiotics in the article entitled "neonatal purulent
      meningoencephalitis complicated with endogenous endophthalmitis in a case"].

PMID- 19099855
TI  - [Application of transnasal intermittent positive pressure ventilation in neonatal
      mechanical ventilation].

PMID- 19099856
TI  - [Concept and significance of acute kidney injury].

PMID- 19099857
TI  - [Effect of sulfur dioxide on pulmonary vascular structure of hypoxic pulmonary
      hypertensive rats].
AB  - OBJECTIVE: Hypoxic pulmonary hypertension is an important pathophysiologic
      process of various cardiovascular diseases. Sulfur dioxide (SO2) was considered
      as a kind of toxic gas previously, but recent studies suggested that SO2 could
      act as a key bioactive molecule in the pathogenesis of cardiovascular diseases.
      Therefore, this study was designed to examine the effect of sulfur dioxide on
      pulmonary vascular structure of hypoxic pulmonary hypertensive rats treated with
      SO2 donor substances. METHODS: The rats were randomly divided into 3 groups:
      control group(n = 8), hypoxic group(n = 8) and hypoxic + SO2 group (n = 10,
      treated with SO2 donor Na2SO3/NaHSO3). The rats of hypoxic group and hypoxic +
      SO2 group were under a hypoxic condition for 21 days, while the rats of control
      group were exposed to room air. The mean pulmonary artery pressure was tested by
      means of right cardiac catheterization and the content of SO2 in plasma was
      investigated by high performance liquid chromatography (HPLC). The change in
      relative medial thickness (RMT) of pulmonary arteries was examined under optical
      microscope. The ultra-structural changes were observed under a transmission
      electron microscope. The data were analyzed through one-way analysis of variance
      (ANOVA) by SPSS 13.0 software. RESULTS: Compared with control group [(2.25 +/-
      0.50) kPa], the mean pulmonary artery pressure of hypoxic group [(5.12 +/- 0.51)
      kPa] raised significantly (t = 5.091, P < 0.01) and RMT of hypoxic group (9.66 +/
      1.27) compared with control group (6.83 +/- 1.57) significantly raised (t =
      3.392, P < 0.01). Ultrastructural observation showed the proliferation and
      degeneration of endothelial cells in small pulmonary arteries in rats with
      pulmonary hypertension. The internal elastic lamina was irregular. The
      proliferation of medial smooth muscle cells of arteries was shown at the level of
      respiratory bronchioles. The collagens also increased. Meanwhile, compared with
      control group [(33.36 +/- 5.62) micromol/L], the content of SO2 in plasma of
      hypoxic group [(27.01 +/- 4.17) micromol/L] declined (t = 2.067, P < 0.05).
      Whereas compared with that of hypoxic group [(5.12 +/- 0.51) kPa], the mean
      pulmonary artery pressure of hypoxic + SO2 group [(3.94 +/- 0.33) kPa] declined
      (t = 2.712, P < 0.01) and RMT of hypoxic + SO2 group (6.97 +/- 1.83) decreased
      compared with hypoxic group (9.66 +/- 1.27) (t = 3.009, P < 0.01). Compared with
      those of hypoxic group, the pulmonary artery ultrastructural changes in hypoxic
      group ameliorated obviously after using exogenous sulfur dioxide donor. The
      endothelial cells became flat and the smooth muscle cells of arteries slightly
      enlarged and arranged regularly. At the same time, compared with hypoxic group
      [(27.01 +/- 4.17) micromol/L], the content of SO2 in plasma of hypoxic + SO2
      group [(29.89 +/- 4.52) micromol/L] raised (t = 1.263, P > 0.05). CONCLUSION:
      Sulfur dioxide plays an important role in the regulation of small pulmonary
      artery structural changes in hypoxic pulmonary hypertensive rats. The hypoxic
      pulmonary hypertensive damages can be ameliorated significantly after using
      exogenous SO2 donor.

PMID- 19099858
TI  - [Effects of platelet activating factor receptor antagonist in intestinal mucin-2
      during endotoxemia on young rats].
AB  - OBJECTIVE: This study aimed to investigate the roles of platelet activating
      factor (PAF) receptor antagonist in damage to intestinal mucin-2 (MUC2) during
      endotoxemia on young rats. METHODS: Eighteen-day-old Wistar rats were randomized
      to be treated with lipopolysaccharide (LPS) (5 mg/kg), LPS plus PAF receptor
      antagonist and normal saline injection (control). PAF receptor antagonist BN52021
      5 mg/kg was administered 30 minutes before or after LPS injection (pretreatment
      group or treatment group). The ileum specimens (n = 8) were harvested at 1.5, 3,
      6, 24, 48 and 72 hours after LPS injection. Transmission electron microscopy was
      used for morphologic evaluation. Immunohistochemistry was used to determine MUC2
      in intestinal mucosa. RESULTS: Microvilli and tight junctions were intact in the
      control group. Enlargement of tight junctions were seen in the LPS group and
      microvilli were thin, rare or disrupted, shed. The rough endoplasmic reticulum,
      mitochondria, and glycogen particles were injured. The changes of the
      pretreatment and treatment group were slightly milder than that in the LPS group.
      Ileum of a control rat in which a thin layer of mucus covering the epithelial
      surface and mucin-containing goblet cells appeared very distended. The experiment
      group showed a decrease or irregularly distributed membranous mucus expression.
      The MUC2 content of absorbance significantly decreased in the LPS challenged
      group compared with that in the control group (P < 0.01), and reached a nadir at
      6 hours (0.1841 +/- 0.0047) vs. the control group (0.2091 +/- 0.0060) (P < 0.01).
      The tendency of the level of MUC2 in the pretreatment and treatment group was the
      same as that of the LPS group, and the level of MUC2 in the pretreatment and
      treatment group was higher than that in the LPS group at each time point. ANOVA
      analysis showed that the inter-group and intra-group difference had statistical
      significance (P < 0.05). CONCLUSIONS: PAF may play some roles in the injury of
      intestinal mucus barrier function during endotoxemia. Preventive and remedial use
      of PAF receptor antagonist BN52021 may relieve intestinal injury.

PMID- 19099859
TI  - [Preliminary study on the effect of carvedilol on children with primary
      endocardial fibroelastosis].
AB  - OBJECTIVE: Endocardial fibroelastosis (EFE), a common pediatric cardiovascular
      disease, often results in chronic heart failure (CHF) and death. Clinical trials
      have shown that the regimen of combining beta-adrenoreceptor blocker with
      traditional medicines against CHF can improve left ventricular function and
      prevent the ventricle from remodeling in patients with CHF. The present study
      aimed to observe the effect of carvedilol on concentration of plasma brain-type
      natriuretic peptide (BNP), and safety in children with EFE. METHODS: Twenty-one
      children with EFE were randomly divided into two groups: (1) treated with
      traditional regimen (digoxin, prednisone and/or diuretics) (n = 10); (2) treated
      with carvedilol plus traditional regimen (n = 11). Measurement of plasma
      concentration of BNP by ELISA, cardiac function by ultrasound were performed
      before and after 6 months of treatment. The changes in clinical symptom, heart
      rate, heart function, side effect and maximal tolerance dose after treatment with
      carvedilol were observed. RESULTS: Plasma concentration of BNP was much higher in
      the group of patients with EFE [(865 +/- 702) ng/L] than that of control group
      [(154 +/- 78) ng/L] (P < 0.01), and there was a positive correlation between
      plasma concentration of BNP and cardiac function classification, and cardiac
      function grades II, III, and IV corresponded to plasma concentration of BNP (286
      +/- 125) ng/L, (437 +/- 386) ng/L, (1673 +/- 859) ng/L respectively in children
      with EFE. Compared with the group treated with traditional medicines, plasma
      concentration of BNP [(403 +/- 216) ng/L vs. (219 +/- 87) ng/L] significantly
      decreased, the clinical symptom was significantly improved, cardio-thoracic ratio
      (CTR) (0.60 +/- 0.05 vs. 0.54 +/- 0.06) (P < 0.05) and heart rate [(115 +/- 20)
      bpm vs. (90 +/- 14) bpm] (P < 0.01) decreased, ejection fraction (EF) (46.6% +/-
      13.4% vs. 54.5% +/- 12.9%), fractional shortening (21.6% +/- 8.1% vs. 24.1% +/-
      7.5%), mean velocity of circumferential fiber shortening [(0.8 +/- 0.5) cir/s vs.
      (0.9 +/- 0.4) cir/s] were significantly increased (P < 0.01), left ventricular
      end-systolic dimension [(34.0 +/- 8.6) mm vs. (32.2 +/- 9.1) mm] (P < 0.05), left
      ventricular mass [(65.9 +/- 34.1) g vs. (65.9 +/- 34.1) g], interventricular
      septal thickness at end-systole [(6.0 +/- 1.0) mm vs (5.5 +/- 1.1) mm] were
      notably decreased (P < 0.01) after treatment with carvedilol. CONCLUSION: These
      data indicated that plasma concentration of BNP significantly increased in
      children with EFE, carvedilol can decrease plasma concentration of BNP, inhibit
      the remodeling of ventricle, significantly improve the cardiac function in
      children with EFE. Carvedilol is effective and safe in treatment of children with
      EFE.

PMID- 19099860
TI  - [Effect of selective alpha1 receptor agonist in the treatment of children with
      postural orthostatic tachycardia syndrome].
AB  - OBJECTIVE: The study was designed to examine the effect of selective alpha1
      receptor agonist midodrine hydrochloride in the treatment of children with
      postural orthostatic tachycardia syndrome. METHODS: Fifty-five children (23 male,
      32 female, age 5 - 19 yrs, mean age 12.3 +/- 3.1 yrs) who came from Peking
      University First Hospital were included in the study and clinical investigations
      as well as standing test, basic head-up tilt test and sublingual nitroglycerin
      provocated head-up tilt test under quiet circumstance were conducted. They were
      randomly divided into treatment group (with midodrine hydrochloride and oral
      rehydration salt treatment) and control group (with oral rehydration salt
      treatment only). At last, the disease-free rate, improvement rate and effective
      rate of symptoms, and the rate of HUT from positive to negative response were
      compared between control group and treatment group. SPSS 10.0 software was used
      for the statistical analysis of these data. RESULTS: The symptom improvement rate
      in treatment group was significantly higher than that of control group after
      three and six weeks of treatment (100.0% vs. 42.4%, P < 0.001; 100.0% vs. 42.4%,
      chi2 = 19.352, P < 0.001). The disease-free rate at follow-up end-point in
      treatment group was significantly higher than that of control group (77.3% vs.
      27.3%, chi2 = 13.239, P < 0.001). The effective rate at follow-up end-point in
      treatment group was also significantly higher than that of control group (100.0%
      vs. 36.4%, chi2 = 22.647, P < 0.001). The rate of HUT changing from positive to
      negative response between two groups after three weeks of treatment was not
      significantly different (31.8% vs. 12.1%, P > 0.05), but it was significantly
      different (81.0% vs. 48.5%, P < 0.05) after six weeks of treatment. CONCLUSION:
      Selective alpha1 receptor agonist midodrine hydrochloride is effective in the
      treatment of children with postural orthostatic tachycardia syndrome.

PMID- 19099861
TI  - [Clinical characteristics and WT1 genetic analysis of patients with steroid
      resistant nephrotic syndrome accompanied with genitourinary malformations].
AB  - OBJECTIVE: To analyze the clinical features and WT1 gene mutations in patients
      with steroid-resistant nephrotic syndrome (SRNS) accompanied with genitourinary
      malformations. The expression of podocyte molecules was also investigated in
      renal specimen of these WT1 mutated patients. METHODS: From January 2005 to May
      2007, 3 cases of SRNS accompanied with genitourinary malformations were involved
      in this study. The expression of podocyte molecules (nephrin, podocin, alpha
      actinin 4, WT1 and CD2AP) in 2 cases was analyzed by immunofluorescence and
      immunohistochemistry; using PCR to amplify genomic DNA and RT-PCR to amplify WT1
      cDNA. GeneScan and GeneScan software were used to quantify the ratio of +KTS/-KTS
      isoforms. RESULTS: The age of onset of the 3 cases were 6 months, 1 year and 10
      years, respectively. The age at diagnosis was 7 months, 9 years and 15 years,
      respectively. The phenotype of case 1 and case 3 was male accompanied with
      genitourinary malformations. Case 2 was phenotypic female. Karyotype analysis of
      the 3 cases revealed 46, XY. Each case was diagnosed as SRNS. Focal segmental
      glomerulosclerosis (FSGS) was confirmed in 2 cases. Podocyte molecular expression
      altered in renal tissues of 2 cases. WT1 staining was negative in case 1. WT1
      expression in case 2 showed a diffuse nuclear staining with less obvious speckles
      compared with controls. WT1 IVS 9 + 5 G > A mutation was detected in case 2 and
      WT1 exon 9 1186 G > A mutation was detected in case 3. No WT1 mutation was
      detected in case 1. CONCLUSIONS: Karyotype analysis and WT1 genetic analyzing
      should be performed for all female patients with early onset SRNS and in male
      patients with SRNS accompanied with genitourinary malformations. The abnormal
      ratio of +KTS/-KTS isoforms caused by WT1 mutations along with abnormal
      expression of podocyte molecules were involved in the pathogenesis of
      proteinuria.

PMID- 19099862
TI  - [Long-term effects of cyclosporine A in children with steroid-resistant
      idiopathic nephrotic syndrome and outcomes of the patients].
AB  - OBJECTIVE: To observe the effects of long-term cyclosporine A (CsA) treatment in
      20 children with steroid-resistant idiopathic nephrotic syndrome (SRNS) and
      analyse the relevant influencing factors of CsA therapy. METHODS: Twenty children
      with SRNS received CsA therapy for 2 years between February 2001 and October 2006
      in the Department of Nephrology. The mean age of children at initiation of CsA
      therapy was 5.5 years (30 months to 12 years). The initial renal histology showed
      minimal change (MCNS) in 15 patients, focal segmental glomerulosclerosis (FSGS)
      in 4 patients and mesangial proliferative glomerulonephritis (MsPGN) in one. The
      starting dose of CsA was 3 - 5 mg/(kg.d), adjusted to maintain a trough level of
      100- 200 microg/L during the first 6 months. After one year, a low dose of CsA 1 
      3 mg/(kg.d) with a trough level of 40 - 70 microg/L was applied to maintain
      remission for 1 year. Liver function, serum albumin, serum cholesterol, serum
      creatinine, urinary NAG/Cr, 24 h urinary protein excretion and CsA whole blood
      trough level of the patients were monitored every one or three months. RESULTS:
      (1) Complete remission (proteinuria < or = 0.1 g/d or negative by dipstick for 3
      consecutive days), partial remission (proteinuria between 0.1 g/d and 50
      mg/(kg.d), serum albumin > or = 30 g/L) and resistance to CsA (proteinuria > or =
      50 mg/(kg.d), or > or = 3+ by dipstick, after 6 months of CsA treatment over a
      trough level of 100 microg/L) were observed in 65%, 20% and 15%, respectively.
      Eleven patients who had complete remission discontinued CsA, in 5 (45%) patients
      the disease relapsed, and resumption of CsA therapy was followed by remission in
      three of them. (2) MCNS showed a 93% response to CsA therapy while non-MCNS
      showed a 60% response, but the difference was not significant (P > 0.05). (3)
      Hypertrichosis, gingival hyperplasia and hypertension occurred in 75%, 25% and
      10% of the patients, respectively. Two patients were found to have renal
      impairment (> 30% rise of serum creatinine) and recovered in 2 weeks. Four
      patients showed a rise of urinary NAG/Cr. The central nervous system adverse
      event occurred in 2 cases. Post-therapy biopsies performed in 3 patients (2 with
      FSGS and one with MCNS) did not show any relevant tubulointerstitial fibrosis.
      Two patients with FSGS of the twenty cases progressed into end-stage renal
      failure. CONCLUSIONS: CsA treatment was confirmed to be effective in children
      with SRNS. Renal fibrosis was rare in patients treated with a low dose of CsA for
      2 years.

PMID- 19099863
TI  - [Summary of the 14th international congress of pediatric nephrology].

PMID- 19099864
TI  - [Summary of the 13th Chinese congress of pediatric nephrology].

PMID- 19099865
TI  - [Analysis of chimeras after allogeneic bone marrow transplantation for beta
      thalassemia major].

PMID- 19099866
TI  - [Changes of peripheral blood dendritic cell functions in children with Henoch
      Schonlein purpura and in vitro effect of Astragalus membranaceus].

PMID- 19099867
TI  - [Experimental study on expression of osteopontin in viral myocarditis].

PMID- 19099869
TI  - [Effects of neural growth factor and hyperbaric oxygen on nerve regeneration
      after hypoxic ischemic brain injury in newborn mice].

PMID- 19099868
TI  - [Effect of antioxidants in hyperoxic lung injury in newborn mice].

PMID- 19099870
TI  - [Expression of neuroglobin in serum of premature neonates and its significance].

PMID- 19099871
TI  - [Neonatal Poland-Moebius syndrome in a case].

PMID- 19099872
TI  - [Invasive Salmonella dublin infection in a case].

PMID- 19099874
TI  - [Advances in noninvasive monitoring of airway inflammation in childhood asthma].

PMID- 19099873
TI  - [Improve continuously the management of childhood asthma].

PMID- 19099875
TI  - [Bacterial etiology of pneumonia in hospitalized children: combined detection
      with culture and polymerase chain reaction].
AB  - OBJECTIVE: Bacterial cultures from respiratory aspirate or sputum have been the
      conventional diagnostic method for pneumonia, but the results of culture was
      often affected by early extensive use of antibiotics, sample collection and
      delivery. The objective of this study was to explore application of the combined
      detection of culture and polymerase chain reaction (PCR) assay in hospitalized
      children with pneumonia. METHODS: Totally 187 hospitalized children with
      pneumonia were enrolled. The age of the patients ranged from 1 month to 10 years,
      124 were male, 63 female; 175 of the patients received antibiotics treatment
      before admission. Deep respiratory aspirate sample from patients was cultured by
      Streptococcus pneumoniae selective plate, Hemophilus influenzae selective plate
      and conventional plate. The aspirate samples were also amplified for DNA of 14
      bacteria with target enriched multiplex polymerase chain reaction (Tem-PCR) and
      detected with Luminex xMAP technology platform. RESULTS: The total positive rate
      by bacterial culture was 40.1% (75/187), of which 17.1% (24/187) were Hemophilus
      influenzae b, 8.6% (16/187) were Escherichia coli, 6.4% (12/187) were Klebsiella
      pneumoniae, 4.8% (9/187) were Staphylococcus aureus, 3.7% (7/187) were
      Streptococcus pneumoniae, 1.6% (3/187) were Pseudomonas aeruginosa, 1.1% (2/187)
      were Acinetobacter baumannii, and 1.1% (2/187) were Enterobacter cloacae. The
      total positive rate by combined detection of culture and Tem-PCR assay were 78.6%
      (147/187), of which 28.9% (54/187) were Hemophilus influenzae b, 19.3% (36/187)
      were Streptococcus pneumoniae, 8.6% (16/187) were Escherichia coli, 6.4% (12/187)
      were Klebsiella pneumoniae, 5.9% (11/187) were Staphylococcus aureus, 5.9%
      (11/187) were Acinetobacter baumannii, 2.7% (5/187) were Pseudomonas aeruginosa,
      and 1.1% (2/187) were Enterobacter cloacae. CONCLUSION: The Tem-PCR assay may
      increase the detection rate of Hemophilus influenzae b, Streptococcus pneumoniae,
      Staphylococcus aureus, Pseudomonas aeruginosa and Acinetobacter baumannii. The
      Combined detection may increase the positive rate of bacterial pathogens in
      hospitalized children with pneumonia, and the results might reflect the real
      patterns of bacterial etiology. The Tem-PCR needs further improvement for
      diagnosis of Escherichia coli and Klebsiella pneumoniae.

PMID- 19099876
TI  - [Clinical studies of children with bronchiolitis obliterans].
AB  - OBJECTIVE: Bronchiolitis obliterans (BO) is a chronic airflow obstruction
      syndrome associated with inflammatory lesions of the small airways. The etiology,
      pathogenesis, effective treatment and prognosis of this disorder remain uncertain
      by now. There has been no large scale clinical research on BO in China. This
      study aimed to analyze the clinical characteristics of BO in children. METHODS:
      Clinical analysis was done on data of 42 patients (31 boys and 11 girls, aged
      from 7 months to 12 years and 2 months) with bronchiolitis obliterans diagnosed
      and treated in Beijing Children's Hospital from April 2001 to August 2007. The
      diagnostic criteria included typical clinical manifestations, specific pulmonary
      CT imaging and lung function tests. RESULTS: All the patients presented with
      persistent cough and wheezing. Crackles and wheezing were heard in most cases.
      Thirty-two (76.2%) cases were post-infectious BO, among whom 8 (25%) were
      supposed to be adenovirus pneumonia, 7 (21.9%) measles pneumonia and 2 (6.2%)
      respiratory syncytial virus infection. In 4 (9.5%) cases BO occurred after Steven
      Johnson syndrome, and 1 (2.4%) after bone marrow transplantation. The
      constrictive obstruction in small airway occurred in 35 cases (89.7%), while
      mixed pattern in 4 (10.3%). Pulmonary CT revealed mosaic perfusion in 34 cases
      (81.0%), bronchiectasis in 14 cases (33.3%), bronchial wall thickening in 14
      cases (33.3%), atelectasis in 4 cases (9.5%) and Swyer-James syndrome in 2 cases
      (4.8%). All the cases received oral corticosteroid and low doses of erythromycin
      or azithromycin, with corticosteroid and bronchodilator inhalation or oral
      montelukast. Follow up time was from 1 month to 5 years. Besides 2 cases in whom
      the disease was ameliorated in clinical presentation, pulmonary imaging and
      function, the rest experienced deterioration and one died. CONCLUSION: In most of
      the patients BO occurred following infections. The specific clinical
      presentations, imaging and pulmonary function are sufficiently informative for
      diagnosis. Most of the cases enrolled in this study had a poor outcome.

PMID- 19099878
TI  - [Guideline for the diagnosis and optimal management of asthma in children].

PMID- 19099877
TI  - [Antioxidative role of peroxiredoxin 6 in acute lung injury].
AB  - OBJECTIVE: To confirm the antioxidant protective effect of peroxiredoxin 6
      (Prdx6) in acute lung injury in mice. METHODS: Lung injury or lung alveolar type
      II epithelial cell (AEC II) injury models were induced in mice by 100% O2
      exposure or H2O2 treatments. Mice and AEC II cell survival rate or BALF analysis
      were applied for evaluating the degree of acute lung injury. Western Blot assay
      was used to determine Prdx6 or Gpx1 protein expression in lung. Annexin V
      staining method was applied to detect cell apoptosis on cultured AEC II cell, and
      thiobarbituric acid reactive substance (TBARS) measurement and diphenyl-1-pyrenyl
      phospholine (DPPP) assays were separately used to measure the level of lipid
      peroxidation in mice lung and AEC II cell membrane. RESULTS: Under 100% O2
      exposure, Prdx6-/- mice presented 24 h shorter survival time compared to wild
      type (WT) mice, on the contrary, Prdx6 gene over-expressed (Tg Prdx6) mice showed
      enhanced mice survival; meanwhile, the degree of AEC II cell injury had H2O2-dose
      dependent pattern with interactive relationship of Prdx6 protection. Under 100%
      O2 exposure for 72 h, it caused 7-fold decreased Gpx1 expression in Prdx6-/-
      mouse lung with no remarkable decrease of Prdx6 expression in Gpx1-/- mice. The
      percentage of apoptotic cells was significantly increased in AEC II cells from
      Prdx6-/- mice, and the percentage of AEC II apoptotic cells from Tg Prdx6 kept
      consistently around 10% under H2O treatments; also, the lipid peroxidation level
      of AEC II cell membrane was the highest in the group of Prdx6-/- mice, which was
      about 2 or 4-fold increased compared to the groups of WT or Tg Prdx6, separately;
      meanwhile, the lipid peroxidation level in Prdx6-/- mice, was also the highest
      compared to the other groups. CONCLUSIONS: Prdx6 plays a critical role in
      defending acute oxidative lung injury and its function of defending cell
      apoptosis and cell membrane lipid peroxidation suggests its unique cell-based
      protective effect.

PMID- 19099879
TI  - [Summary of the 2nd session of the national pediatric bronchoscopy academic
      forums and continuing education course].

PMID- 19099880
TI  - [Overview of algorithm for diagnosis and treatment of chronic cough in children:
      Intensive reading of the guideline for diagnosis and treatment of chronic cough
      in pediatrics (I)].

PMID- 19099881
TI  - [Establishment and validation of predictive model of short term responses to
      recombinant human growth hormone treatment in prepubertal short stature children
      with various growth hormone secretary statuses].
AB  - It has been proved that to analyze the factors that determine responsiveness to
      rhGH and to develop growth prediction models can help doctors to individualize
      the treatment and maximize the effect. OBJECTIVES: To set up and validate the
      predictive models of growth responses to rhGH treatment in the first year in
      prepubertal short stature children with various GH secretary statuses. METHODS:
      Growth responses to rhGH treatment in the first year, height velocities (HV) and
      increases in height SDS (DeltaHtSDS), in 62 prepubertal short stature children
      with various GH secretary statuses were analyzed retrospectively. There were 27
      patients with complete growth hormone deficiency (cGHD), 23 with partial GHD
      (pGHD) and 12 with idiopathic short stature (ISS) in the model group. According
      to the peak GH value in GH provocative test, the group of pGHD was divided into
      pGHD-1 (5 - 6.9 microg/L, 12 patients) and pGHD-2 (7 - 9.9 microg/L, 11
      patients). All the cases in model group were used for setting up Model-total and
      the cases of growth hormone deficiency for Model-GHD. Predictive models,
      including Model-GHD and Model-total, to HV and DeltaHtSDS were set up by the way
      of multiple regression analysis, based on the results of simple correlation
      analysis. Other 14 children were included according to the same criteria with the
      model group, the validation group. The validation group was analyzed
      prospectively. The actual growth responses were compared with the predicted
      values calculated by different models so that the predictive models could be
      validated. RESULTS: The simple correlation analysis showed that HV and DeltaHtSDS
      in the first year were negatively correlated with the same group factors at
      baseline: chronological age, bone age, height SDS, differences between the height
      SDS and the target height SDS, peak value in GH provocative test and IGF-1SDS.
      All the 4 predictive models were found to be significant at a level of P < 0.05,
      R(2) ranged from 0.244 to 0.519. The two models predicted HV and Model-GHD for
      DeltaHtSDS were proved to be validated. The observed and predicted responses
      positively and significantly correlated with each other, r value ranged from
      0.753 to 0.996. And there was no significant difference between them when tested
      by paired t test. CONCLUSIONS: The availability of the predictive model will help
      to individualize the growth hormone treatment in prepubertal short stature
      children with various growth hormone secretary status.

PMID- 19099882
TI  - [Effect of blood pressure status changes from childhood to adulthood on
      hypertension related cardiac-renal function in adulthood].
AB  - OBJECTIVE: To assess the effect of blood pressure (BP) changes from childhood to
      adulthood on hypertension related cardiac and renal function in adulthood.
      METHODS: The "Beijing children and adolescents BP study cohort" consists of 2505
      subjects 6-18 years of age who were enrolled in the baseline BP investigation in
      1987. Among them, 412 individuals aged 23-37 years were successfully followed up
      in 2005. In this study, clinical examinations and questionnaire survey about risk
      factors of cardiovascular disease (CVD) were carried out. RESULTS: Among 412
      adults, the prevalence rate of hypertension was 14.8% (61/412); 83.6% of persons
      with hypertension were overweight or had obesity. Hypertension related cardiac
      and renal functional abnormalities were relatively common (72.1%) clinical signs
      among this adult population. With BP level elevation, cardiac and renal functions
      damage became more severe. The morbidity of cardiac and renal functional
      abnormalities in those who were hypertensive in childhood and were not
      hypertensive in adulthood was similar to those who were not hypertensive at both
      times. The morbidity of microalbuminuria and abnormalities in electrocardiogram
      (ECG) were higher in those who were hypertensive at both times than those who had
      appropriate BP levels in childhood and became hypertensive in adulthood. Adjusted
      for age, gender, BMI and body surface area (BSA) during adulthood, the left
      ventricular end-diastolic dimension (LVd), the left ventricular mass (LVM), the
      intraventricular septal thickness (IVST), the left ventricular posterior wall
      thickness (LVPWT) in the group of hypertension were higher than that in the group
      which was not hypertensive, and the ejection fraction (EF) was lower in the group
      of hypertension in adulthood. The LVd, LVM, IVST, LVPWT and EF in those who were
      hypertensive in childhood and were not hypertensive in adulthood were similar to
      those who were not hypertensive at both times. Logistic regression analysis
      showed that persons who were hypertensive in childhood and remained so during
      adulthood were at an increased risk of cardiac and renal functional damage (OR =
      4.072, 95% CI = 1.472 - 11.266). Those who were hypertensive in childhood and
      became normotensive in adulthood did not have significant abnormalities in
      cardiac and renal functions (OR = 1.086, 95% CI = 0.514 - 2.298, chi2 = 0.047, P
      = 0.828). CONCLUSION: Persons who were hypertensive at both times were at an
      increased risk of cardiac and renal function damage. Those who were hypertensive
      in childhood and became normotensive in adulthood did not have significant
      abnormalities in cardiac and renal functions. Thus prevention and control of
      hypertension in children and adolescents may have important beneficial effects on
      prevention of CVD in adulthood.

PMID- 19099883
TI  - [Clinical features and SCN1A gene mutation analysis of severe myoclonic epilepsy
      of infancy].
AB  - OBJECTIVE: Severe myoclonic epilepsy of infancy (SMEI), or Dravet syndrome, is a
      severe epileptic encephalopathy. This study aimed to investigate the clinical
      features and genetic diagnosis of SMEI. METHODS: The electroclinical data and the
      mutation of SCN1A gene in 13 children with SMEI were analyzed. RESULTS: Of the 13
      children, 10 were males and 3 were females. Eight of them had family history of
      febrile seizures. The average age of seizure onset was 5.6 months, with a range
      of 2 to 9 months. The initial seizure was a febrile seizure in 9 patients (69%).
      Generalized or hemiclonic seizures were often triggered by fever. Eight patients
      had a history of febrile status. Afebrile seizures occurred from 2 months to 21
      months of age. All patients went on to develop multiple seizure types.
      Generalized tonic clonus seizures (GTCS) were found in 11, partial seizures in
      12, atypical absence in 10. Myoclonic seizures were presented in all patients.
      Twelve patients had 3 or more seizure types. Seizures of all patients had a
      characteristic of temperature sensitivity. The precipitating factors included
      fever, hot bath and vaccination. Nine patients (69%) had a history of status
      epilepticus. Delay in mental development was present in 11 cases, ataxia in 5 and
      pyramidal sign in 2. EEG was normal in most patients in the first year of life,
      followed by generalized, focal and multifocal discharges. Brain MRI was abnormal
      in 2 cases. Seizures were not completely controlled in all patients.
      Carbamazepine and lamotrigine aggravated seizures in some patients. SCN1A gene
      mutation was found in 10 cases, including seven missense mutations, two nonsense
      mutations and one frame shift mutation. CONCLUSION: The clinical features of SMEI
      were seizure onset within one year of age, first event is often a febrile
      seizure; multiple seizure types and mental delay occurred after the second year
      of life; seizures have a characteristic of temperature sensitivity; EEG was
      normal in the first year of life, followed by generalized, focal or multifocal
      discharges; early diagnosis by testing SCN1A mutation guides selection of
      antiepileptic drugs.

PMID- 19099884
TI  - [Pathological change of partial liquid ventilation in a rabbit meconium
      aspiration lung injury model].
AB  - OBJECTIVE: To observe the pathological change of partial liquid ventilation (PLV)
      through establishing the rabbit model of acute lung injury (ALI) induced by
      meconium aspiration. METHODS: Adult, healthy male or female New Zealand white
      rabbits were randomly allocated into six groups as follows: (1) control group,
      (2) conventional mechanical ventilation (CMV) group, (3) high-frequency
      oscillatory ventilation (HFOV) group, (4) CMV combined with PLV group, (5) HFOV
      combined with PLV group and (6) normal group. The animals were anesthetized with
      1% pentobarbital and tracheotomy was performed and endotracheal tube was placed,
      20% meconium fluid (3 ml/kg) was quickly injected into the lung through the
      endotracheal tube and arterial blood gas was analyzed 30 minutes later. ALI was
      indicated when P/F ratio (PaO2)/FiO(2)) was < or = 300 mm Hg (1 mm Hg = 0.133
      kPa) and Cdyn Dynamic Compliance declined by more than 30% of the baseline. The
      animals were then randomly allocated into one of the 6 groups. In PLV groups
      (including CMV + PLV and HFOV + PLV) warmed (37 degrees C) and oxygenated
      perfluorocarbon was slowly instilled into the lungs of the rabbits through the
      endotracheal tube at a low-dose 3 ml/kg, then set 15-min positive pressure by
      sacculus proprius to guarantee perfluorocarbon to steadily diffuse in to the
      lungs. Six hours after ventilation the animals were sacrificed by using overdose
      of room air instillation via vein. The lungs were taken and fixed in 4%
      paraformaldehyde (PFA) and were stained with hematoxylin-eosin (HE). Pathological
      evaluations included inflammatory manifestation, edema and hemorrhage in both
      alveolar and interstitial area, damages of small airway (alveolar tube and
      alveolar bursa) and hyaline membrane formation. One way analysis of variance,
      Student Newman-Keuls (SNK) method and Kruskal-Wallis (K-W) test were used for
      comparisons. RESULTS: With the exception of normal group 30 minutes after
      meconium injections blood gas analysis in different groups showed significant
      changes and PaO(2)/FiO(2) (< 300 mm Hg), Cdyn declined by more than 60% compared
      with baseline (P < 0.05). The pathological analysis showed that alveolar and
      interstitial inflammation, edema, alveolar and interstitial hemorrhage, and small
      airway damage existed in each group. The hyaline membrane formation was found in
      one of CMV + PLV group rabbits. The perfluorocarbon-treated animals (CMV + PLV
      and HFOV + PLV) showed significantly less injury in dependent lung and less
      damage of small airway (CMV + PLV or HFOV + PLV vs. CMV = 1.1 +/- 0.4 or 0.9 +/-
      0.3 vs 2.6 +/- 0.5) compared with the animals of CMV group (P < 0.01). HFOV group
      (2.1 +/- 0.3) also had less alveolar and interstitial inflammation compared with
      CMV group (3.0 +/- 0) (P < 0.05), and there was less evidence of alveolar and
      interstitial edema in the animals treated with HFOV + PLV (1.0 +/- 0.7) compared
      with CMV (2.0 +/- 0.8) (P < 0.01). Treatment with perfluorocarbon did not result
      in significant difference in alveolar and interstitial hemorrhage. Compared with
      CMV and HFOV groups, the groups treated with PLV showed lower mortality of
      animals (21.4% and 14.3%). CONCLUSIONS: PLV can alleviate the histological damage
      of acute lung injury induced by meconium aspiration and increased survival chance
      and therefore PLV would be a useful treatment for MAS. The effectiveness and
      safety of application of PLV should be evaluated in clinical studies.

PMID- 19099885
TI  - [Application of electrical impedance equipment in evaluating local lung volume
      during different PEEP ventilation and at different respiratory rate].
AB  - OBJECTIVE: To evaluate the applicability of electrical impedance equipment in
      assessing local lung volume during different PEEP ventilation and at different
      respiratory rate in neonatal piglets. METHODS: Electrical impedance measurements
      (EIM) were performed on 6 healthy newborn piglets (age 4 +/- 1 d, weight 1.66 +/-
      0.31 kg) using 8 electrodes distributed to 4 quadrants of the lung (left, right,
      upper, lower). Tidal impedance and functional residual impedance changes during
      PEEP levels of 2, 4, 6 and 8 cm H2O and frequencies ranging from 0.5 to 15 Hz
      were investigated. RESULTS: The sum of regional tidal impedance obtained from
      four quadrants, significantly reflected tidal volume (VT) measured by a
      pneumotachograph during both frequency and PEEP changed (r2 = 0.98). A decrease
      of PEEP 4 to 2 cm H2O caused a significant increase in total tidal impedance
      (TTI) as well as in VT (P < 0.01 and P < 0.05); whereas an increase in frequency
      from 0.5 to 15 Hz was associated with a significant decrease in both TTI and VT
      (P < 0.05 and P < 0.01). Increased frequency had a balancing effect on air
      distribution, whereas higher PEEP did not result in more homogeneous ventilation.
      Minimal impedance values (FRI) (surrogate variable for FRC) showed that total FRI
      significantly decreased with increasing PEEP level. CONCLUSIONS: EIM demonstrated
      good applicability to assess changes in thoracic gas volume. It is highly
      suggested that this method could be considered and further studied as a non
      invasive bedside method to monitor continuously regional lung ventilation of
      neonates under any mode of mechanical ventilation.

PMID- 19099886
TI  - [Effect of neonatal BCG vaccination on phenotype and function of splenic
      dendritic cells of BALB/c mice].
AB  - OBJECTIVE: The impact of dendritic cells (DCs) and regulatory T cells (Tr) on the
      pathogenesis of asthma have been investigated over the past decades. As the
      professional antigen presenting cells, DCs not only prime immune response
      directing Th0 cells toward different T subtypes but also induce immune tolerance.
      As an immunoregulator, Bacillus Calmette-Guerin (BCG) has potential to be applied
      in allergic diseases such as asthma for prevention. Previous study showed that
      neonatal BCG vaccination could induce Th1/Tr1 development in mice in vivo. To
      further identify the mechanism of neonatal BCG vaccination on T cell subsets
      differentiation, the present study was designed to investigate the impact of BCG
      vaccination on splenic DCs development in neonatal mice. METHODS: Neonatal
      specific pathogen free (SPF) BALB/c mice (2-3 days) were divided into
      intraperitoneal BCG-treated group, subcutaneous BCG-treated group and control
      group; simultaneously adult SPF BALB/c mice (6-8 weeks) were divided into
      intraperitoneal BCG-treated and control group. The BCG-treated mice were
      inoculated with 1 x 10(5) CFU BCG, the mice in control group were not inoculated
      with any vaccine. Four weeks post BCG vaccination, spleen cells were isolated.
      With flow cytometry, subtype and maturity of splenic DCs were analysed. Moreover,
      cells were further separated into mononuclear cell by Ficoll solution. The
      mononuclear cells were stimulated by 1 microg/ml lipopolysaccharide (LPS) for 18
      or 10(5) CFU /ml BCG for 48 hours at 37 degrees C in a humidified atmosphere
      containing 5% CO2 and cytokines concentration was detected by ELISA. RESULTS: (1)
      CD11c(+) CD8alpha(+) and CD11c(+) CD8alpha(-) DCs were found in spleen cells of
      the BALB/c mice. In comparison with the control group, the percent of CD11c(+)
      CD8alpha(-) DCs in intraperitoneal BCG group significantly declined (P < 0.01)
      and that of CD11c(+) CD8alpha(+) DCs significantly increased (P < 0.01), there
      were no significant difference in DC subtypes between intraperitoneal and
      subcutaneous BCG-vaccinated mice. In contrast, the percent of CD11c(+) CD8alpha(
      )DCs markedly increased (P < 0.01) and that of CD11c(+) CD8alpha(+)DCs noticeably
      reduced (P < 0.01) in adult BCG-vaccinated mice. The percent of CD11c(+)CD8alpha(
      )DC was significantly higher and that of CD11c(+) CD8alpha(+)DC was significantly
      lower in adult-vaccinated BALB/c mice than that of neonatal-vaccinated ones. (2)
      The expression of costimulatory molecules CD40 on CD11c(+) CD8alpha(-) DCs and
      CD86 on CD11c(+) CD8alpha(+) DCs in neonatal BCG-treated BALB/c mice was higher
      than the controls. There were no significant difference in expression of
      costimulatory molecules on DC between neonatal BCG-vaccinated mice. Compared with
      the control group, expression of CD40 and MHC-II molecules on CD11c(+) CD8alpha(
      ) and CD11c(+) CD8alpha(+)DC was significantly higher and that of CD86 was
      significantly lower in adult BCG-vaccinated mice. The expression of costimulatory
      molecules on DC had no significant difference between neonatal and adult BCG
      vaccinated BALB/c mice. (3) As compared with the control mice, concentration of
      IL-12p70 induced by LPS and IL-10 induced by BCG in vitro from spleen cells
      culture supernatant was noticeably elevated (P < 0.05) in neonatal BCG-treated
      BALB/c mice, but that of IL-6 did not change by LPS or BCG stimulation.
      CONCLUSION: (1) By up-regulating splenic CD8alpha(+)DCs and inducing IL-12p70 and
      IL-10 production in BALB/c mice, neonatal BCG vaccination promoted Th1/Tr1
      development. (2) The effect of BCG vaccination on DC was different between
      neonates and adult BALB/c mice.

PMID- 19099887
TI  - [Changes of cerebrovascular blood flow dynamics in fetuses with congenital heart
      disease].

PMID- 19099888
TI  - [Childhood Budd-Chiari syndrome in 3 cases].

PMID- 19099889
TI  - [Topiramate loading for treatment of a case with status epilepticus].

PMID- 19099890
TI  - [Progresses in noninvasive imaging of myocarditis].

PMID- 19099892
TI  - [Improve diagnosis and treatment of primary immunodeficiency disease in China].

PMID- 19099891
TI  - [Sodium channel alpha-1-subunit gene mutations and epilepsy].

PMID- 19099893
TI  - [Strategy of infant feeding during mass].

PMID- 19099894
TI  - [Get inspiration from the event of urinary system stones induced by melamine].

PMID- 19099895
TI  - [Melamine related urinary calculus and acute renal failure in infants].
AB  - OBJECTIVE: To summarize clinical characteristics, diagnosis and treatment of
      infants with urinary calculus and acute renal failure developed after being fed
      with melamine tainted formula milk. METHODS: Data of infant patients with urinary
      calculus and acute renal failure due to melamine tainted formula milk admitted to
      the Beijing Children's Hospital affiliated to the Capital Medical University and
      the Xuzhou Children's Hospital in 2008 were used to analyze the epidemiological
      characteristics, clinical manifestations, image features as well as effects of 4
      types of therapies. RESULTS: All the 34 infants with urinary calculus were
      complicated with acute renal failure, their blood urea nitrogen (BUN) was (24.1
      +/- 8.2) mmol/L and creatinine (Cr) was (384.2 +/- 201.2) micromol/L. The
      chemical analysis on the urinary calculus sampled from 14 of the infants showed
      that the calculus contained melamine and acidum uricum. The time needed for the
      four types of therapies for returning Cr to normal was (3.5 +/- 1.9) d for
      cystoscopy group, (2.7 +/- 1.1) d for lithotomy group, (3.8 +/- 2.3) d for
      dialysis group, and (2.7 +/- 1.6) d for medical treatment group, which had no
      statistically significant difference (P = 0.508). Renal failure of all the 34
      infants was relieved within 1 to 7 days, averaging (3.0 +/- 1.8) d. CONCLUSION:
      Melamine tainted formula milk may cause urinary calculus and obstructive acute
      renal failure. It is suggested that firstly the patients with urinary calculus
      complicated with acute renal failure should be treated with dialysis or
      medication to correct electrolyte disturbances, in particular hyperkalemia, and
      then relieve the obstruction with available medical and surgical methods as soon
      as possible. It is observed that the short term prognosis is satisfactory.

PMID- 19099896
TI  - [Explanation on "the treatment of the urinary calculus of the infant fed with
      melamine polluted formula milk"].

PMID- 19099897
TI  - [Chronic cough and asthma in children: intensive reading of the Guideline for
      diagnosis and treatment of chronic cough in pediatrics (II)].

PMID- 19099898
TI  - [Clinical analysis of pulmonary arterial hypertension secondary to connective
      tissue disease in children].
AB  - OBJECTIVE: To study the epidemiology, clinical characteristics and prognosis of
      children with pulmonary arterial hypertension (PAH) secondary to connective
      tissue disease (CTD). METHODS: The clinical record files of the pediatric
      inpatient with PAH in the population of CTD in the hospital treated between
      January 2000 and January 2007 were analyzed retrospectively. RESULTS: (1) In 299
      patients with CTD and complete Doppler echocardiography files, 31 (31/299, 10.4%)
      patients (28 females and 3 males), aged from 7 to 18 years (average: 12.5 years),
      were found to have PAH, in whom, 5(62.5%)in 8 patients with overlapped CTD
      (OCTD), 2 (50.0%) in 4 patients with antiphospholipid syndrome (APS), 4(28.6%) in
      14 patients with systematic vasculitis (SV), 3 (10.7%) in 28 patients with
      dermatomyositis (DM), 17(7.6%) in 223 systemic lupus erythematosus (SLE) had PAH.
      The CTD-associated PAH occurred in the 3rd week to 5th year after initial CTD
      manifestations (median onset: 1.5 years). (2) The onset of CTD-associated PAH was
      obscure and children with severe CTD-associated PAH presented with dyspnea
      (18/31, 58.1%) and heart failure (9/31, 29.0%). The children with Raynaud's
      phenomenon or positive anticardiophospholipid antibody (ACL) or positive lupus
      anticoagulant (LA) were prone to have more severe PAH. (3) Doppler
      echocardiography and pulmonary function test, especially the test of pulmonary
      diffusion function of CO (D(LCO)) were necessary to detect PAH early. (4) After
      treatment, the pulmonary arterial pressure in mild and moderate PAH cases could
      be normalized and in severe PAH cases could be decreased to mild or moderate
      levels. There was a lower PaO(2) level (P < 0.01), a higher pulmonary arterial
      systolic pressure (PASP) level (P < 0.05) in the cases of CTD-PAH who died as
      compared with the live patients. CONCLUSIONS: PAH is a common complication of
      CTDs, which occurs often 1.5 years after initial CTD manifestations. The early
      associated symptom is obscure and the severe cases manifest with dyspnea and
      heart failure. Those with Raynaud's phenomenon and positive ACL and LA are prone
      to develop more severe PAH. Early and regular Doppler echocardiography and
      pulmonary function test are necessary to detect PAH early. Severe CTD associated
      PAH in children could lead to poor outcome. PASP classification and PaO(2) level
      are important factors affecting prognosis.

PMID- 19099899
TI  - [Evaluation of tissue strain and strain rate imaging for left heart function in
      children with systemic lupus erythematosus].
AB  - OBJECTIVE: To investigate the diagnostic value of the tissue strain imaging in
      myocardial dysfunction in children with systemic lupus erythematosus (SLE).
      METHODS: 24 patients with SLE and 32 healthy controls underwent conventional and
      tissue Doppler echocardiography. Peak strain and strain rate value during
      systolic and diastolic phases as well as E/A, LVFS, LVEF were measured in both
      SLE and the control group subjects. RESULTS: The E/A, LVFS and LVEF did not
      significantly differ between SLE children and controls (P > 0.05). The systolic
      peak strains and strain rates of SLE children were lower than those of the
      controls but there was no significant difference (P > 0.05). The diastolic peak
      strains and strain rates of SLE children were significantly lower than those of
      the controls (P < 0.01). The diastolic peak strains and strain rates of
      anticardiolipin antibodies (aCL) positive children were significantly lower than
      the aCL negative ones (P < 0.05). CONCLUSION: Strain and strain rate combined
      with aCL could sensitively detect myocardial dysfunction of children with SLE.

PMID- 19099900
TI  - [Effect of the serum panel reactive antibody on proliferation and differentiation
      of cord blood CD34+ cells in vitro].
AB  - OBJECTIVE: The low rate of engraftment in children with beta-thalassemia has
      seriously restricted the popularity of the hematopoietic stem cell
      transplantation (HSCT). Panel reactive antibody (PRA) has been regarded as one of
      the important factors for the success of kidney transplantation. Poly-transfusion
      before transplantation is associated with the production of PRA. Also PRA is
      produced in the children with beta-thalassemia major who need poly-transfusion
      for life. PRA might be one of factors inducing the low rate of engraftment in
      children with beta-thalassemia. This study focused on observing the effect of PRA
      on the proliferation, differentiation, apoptosis and necrosis of cord blood
      CD34(+) cells in vitro by incubating the cord blood CD34(+) cells with serum
      containing PRA. METHOD: Seven samples of cord blood were collected and the HLA
      typing for every sample was done. Seven sera positive for PRA and seven negative
      sera were selected respectively. Mononuclear cells (MNCs) were obtained by Ficoll
      Hypaque density gradient centrifugation. CD34(+) cells were isolated from MNCs by
      positive selection using an immunomagnetic separation (CD34(+) progenitor cell
      isolation kit and auto-MACS). The CD34(+) cells of umbilical cord blood were
      incubated with the serum and complement in the following groups: A (absence of
      serum), B (presence of PRA positive serum), C (presence of PRA positive serum and
      complement), D (presence of complement), and E (presence of PRA negative serum).
      After incubation the samples were centrifuged and the supernatant was collected
      for LDH detection. At the same time the CD34(+) cells were harvested for
      assessing the expression of Annexin V and CD95 of the CD34(+) cells by flow
      cytometry and also for the detection of the DNA synthesis by (3)H-TaR
      incorporation. Meanwhile the cells were inoculated into the methylcellulose
      cultural system. The proliferation and hematopoietic potential of the CD34(+)
      cell of cord blood by the colony formation assay were detected on the day 10.
      RESULT: The concentration of LDH in group A was (20.71 +/- 2.81) U/L, which was
      significantly lower than that in group B (64.28 +/- 5.12) U/L and group C (84.29
      +/- 4.99) U/L. The concentration of LDH in group B was significantly lower than
      that in group C, while there were no significant differences in the concentration
      of LDH among groups A, D and E (P > 0.05). The cpm in group A was (22 629 +/-
      3288), which was significantly higher than that in group B (4598 +/- 2178) and
      group C (1626 +/- 1192). And the cpm in group B was significantly higher than
      that in group C. There were no significant differences in the cpm among groups A,
      D and E (P > 0.05). On day 10 of culture, the total colonies, granulocyte
      macrophage colony forming unit (CFU-GM), mixed colony forming unit (CFU-GEMM) and
      erythroid burst colony forming unit (BFU-E) in group A were significantly higher
      than that in group B and C. The total colonies, CFU-GM and CFU-GEMM in group B
      were significantly higher than those in group C. No significant differences were
      found in the total colonies, CFU-GM, CFU-GEMM and BFU-E among groups A, D and E
      (P > 0.05). There were no statistically significant differences in the CD95 and
      Annexin V expression among all the groups (P > 0.05). CONCLUSION: PRA could
      impair the membrane, decrease the DNA synthesis, and inhibit the colony formation
      of CD34(+) cord blood cells, which could be strengthened by the presence of the
      complement at the given concentration in our study. PRA had no significant
      influence on the apoptosis of CD34(+) cells in vitro.

PMID- 19099902
TI  - [Autoinflammatory disease].

PMID- 19099903
TI  - [Diagnosis and treatment of pulmonary arterial hypertension associated connective
      tissue diseases in children].

PMID- 19099901
TI  - [Effects of small interfering RNA (siRNA) against Par-4 gene on the apoptosis of
      human bone marrow mesenchymal stem cells].
AB  - OBJECTIVE: The prostate apoptosis response factor-4 (Par-4) gene was originally
      identified by differential screening for genes that are up-regulated when
      prostate cells are induced to undergo apoptosis. Par-4 was found to possess
      potent apoptotic activity in various cellular systems in response to numerous
      stimuli. The aim of this study was to explore the effects of small interfering
      RNA (siRNA) against Par-4 gene on the apoptosis of human bone marrow mesenchymal
      stem cells (hBMSCs) exposed to glutamate. METHODS: Primary culture of hBMSCs was
      carried out and siRNAs targeted Par-4 gene (Par-4-SiRNA) were chemically
      synthesized. Eukaryocytic expression vector was built and were transfected into
      hBMSCs with liposome. After selecting with G418, the stable cell clones were
      treated with glutamate. The expression of Par-4 mRNA was determined by real-time
      PCR. The apoptosis of hBMSCs was quantified by flow cytometry. Western blotting
      was used to detect the protein levels of phosphorylated Akt1 (Thr308). Relative
      Caspase-3 activity was determined by colorimetric assay. RESULTS: The Par-4-SiRNA
      1 and Par-4-siRNA-2 could markedly down-regulate the mRNA levels of Par-4 gene in
      hBMSCs. With the transfections of Par-4-SiRNA-1 and Par-4-SiRNA-2, the levels of
      Par-4 mRNA were respectively decreased by 88% and 67%. Both Par-4-SiRNA-1 and Par
      4-SiRNA-2 inhibited significantly the apoptosis of hBMSCs induced by glutamate,
      in which the percentages of apoptotic cells were respectively decreased to 38.80%
      +/- 3.97% (P < 0.01) and 45.49% +/- 4.32% (P < 0.01) from 60.30% +/- 6.82%.
      Western blot assays demonstrated that, glutamate down-regulated the expression of
      phosphorylated Akt1 proteins in hBMSCs (89.07 +/- 6.42 and 28.30 +/- 5.65,
      respectively, P < 0.01). However, Par-4-SiRNA-1 and Par-4-SiRNA-2 could markedly
      recover the down-regulation of Akt1 proteins induced by glutamate (63.56 +/- 6.75
      and 45.59 +/- 4.88, respectively, P < 0.01). And the relative Caspase-3 activity
      which was enhanced by the treatment with glutamate (0.1428 +/- 0.0495 and 0.8616
      +/- 0.1051, P < 0.01), was suppressed by Par-4-SiRNA-1 and Par-4-SiRNA-2 (0.8616
      +/- 0.1051 and 0.6581 +/- 0.0555, respectively, P < 0.01). CONCLUSION: SiRNA
      against Par-4 gene could inhibit the apoptosis of hBMSCs induced by glutamate,
      and its inhibitory effects may be mediated by the up-regulation of phosphorylated
      Akt1 and the suppression of the relative Caspase-3 activity.

PMID- 19099904
TI  - [Reference values of differences between TW3-C RUS and TW3-C Carpal bone ages of
      children from five cities of China].
AB  - OBJECTIVE: The determination of skeletal maturity has an important role in
      pediatric clinical practice, especially in relation to endocrinological problems
      and growth disorders, and it is frequently useful in diagnosis and monitoring
      treatment. It has been suggested that the difference between radius, ulna and
      short bonse (RUS) and carpal may be of differential diagnostic significance.
      However, no data on comparison among bone ages of Chinese children are available.
      The differences between TW3-Chinese RUS (TW3-C RUS) and TW3-Chinese Carpal (TW3-C
      Carpal) bone age of Chinese children were observed in this study to provide
      references for skeletal development estimation. METHODS: Totally 9408 Han healthy
      children (5066 boys, 4302 girls) aged 1.5 - 13.5 years from 5 cities of China
      were enrolled in this study. The bone ages of the children were estimated by TW3
      C RUS and TW3-C Carpal. The Z score curves of the differences between them were
      fitted by BCPE distribution and the goodness-of-fit of Box-Cox power exponential
      distribution (BCPE) models were assessed by Q-test and percents of cases of
      sample below the fitted percentile curves. RESULTS: The means of the differences
      between TW3-C RUS and TW3-C Carpal were -0.19 - 0.17 over the age 2.0 - 13.5
      years in boys and -0.12 - 0.13 from age 1.5 - 11.5 years in girls. The standard
      deviations were respectively 0.47 - 1.01 years for boys and 0.49 - 0.82 years for
      girls. The degrees of freedom, with respect to the parameter curves from BCPE
      distribution, were selected and the percentile curves were fitted by BCPE. The
      differences between percents of cases below the fitted percentile curves and
      expected values were all under 0.66%, exception of difference for 90th percentile
      in girls. CONCLUSIONS: The differences between TW3-C RUS and TW3-C Carpal varied
      with age, the standard deviations increased gradually before 4.5 years of age in
      boys and 4 years of age in girls, and afterwards the variations decreased
      steadily until the TW3-C Carpal has reached full maturity. However, there was sex
      diversity in the extent of the variations. The differences between TW3-C RUS and
      TW3-C Carpal for boys were evidently greater than that for girls. The sex
      difference decreased progressively after 10 years. The proposed Z scores curves
      charts should provide reference for clinical practice.

PMID- 19099905
TI  - [Clinical and biopsy-based myopathological features of 5 cases with centronuclear
      myopathy].
AB  - OBJECTIVE: To analyze the clinical and pathological features of the centronuclear
      myopathy (CNM) in 5 Chinese patients and evaluate their diagnostic and
      differential diagnostic value. METHODS: A standard series of histochemical and
      enzymohistochemical investigations were performed on all muscle specimens of CNM
      cases obtained via biopsy. The clinical manifestations and myopathological
      features of 5 CNM patients were retrospectively analyzed. RESULTS: The age of
      onset ranged from 3 to 12 years. All patients primarily presented with limb
      girdle muscle weakness. In 3 patients extraocular muscles, facial muscles and
      cervical muscles were affected, respectively. The proximal muscles were affected
      more seriously than the distal and the lower limbs more seriously than the upper.
      Tendon reflex was reduced and no evident muscular atrophy was seen. The course of
      the disease ranged from 4 to 46 years and progressed slowly. The ability of
      walking could be maintained for many years and the fast movements such as running
      and jumping were impaired early. The serum creatine kinase (CK) level was normal
      or elevated slightly. Electromyography showed myopathic pattern in all cases. Two
      patients (mother and son) were from the same family and the son's two siblings
      had similar symptoms indicating autosomal dominant inherited pattern. There was
      mild variation in fiber size and most small fibers were round. Interstitial
      tissue increase slightly. Fibers with centrally placed nuclei accounted for 23% -
      93%. Neither necrotic and regenerated fibers nor infiltration of inflammatory
      cells were seen. Type I fiber predominance and hypotrophy were present in all
      patients. Abnormal arrangement of the sarcoplasmic strands in appearance of
      "spokes of a wheel", increased oxidative enzyme activity around centronuclear and
      perinuclear halo were observed in 2 patients by NADH-TR staining. CONCLUSIONS:
      For the patients who had the onset during the childhood and presented with slow
      progressive limb girdle muscle weakness, disability of fast movements and normal
      serum CK level, the possibility of benign congenital myopathy should be
      considered. High percentage of centronuclear fibers as well as type I fiber
      predominance and hypotrophy in muscle biopsy pathology may provide a
      morphological evidence for the definite diagnosis of CNM.

PMID- 19099906
TI  - [Transcatheter intervention for critical pulmonary artery valvular stenosis and
      atresia with intact ventricular septum in neonates].
AB  - OBJECTIVE: To assess the feasibility of transcatheter intervention for critical
      pulmonary arterial valve stenosis and atresia with intact ventricular septum in
      neonates. METHODS: From June 2006 to January 2008, 13 neonates (9 with critical
      pulmonary arterial valve stenosis, 4 with pulmonary arterial valve atresia)
      underwent transcatheter intervention(one of them was premature neonate). Ten of
      the patients were boys and 3 were girls. The mean age was (17.4 +/- 10.7) days.
      The mean weight was (3.4 +/- 0.8) kg. All the patients received prostaglandin
      E(1) infusion to dilate the ductus arteriosus before and during the procedure.
      Valvuloplasty was performed using a low-profile balloon (2.5 - 4.0 mm in
      diameter), and then a balloon approximately 1.0-1.2 times the annulus diameter
      was applied. In patients with pulmonary atresia, the valve was perforated with a
      radiofrequency wire, and then valvuloplasty was performed. RESULTS: Twelve
      patients (92%) were successfully treated with transcatheter intervention. Right
      ventricular systolic pressure decreased by 50% [from (120.1 +/- 17.0) mm Hg (1 mm
      Hg = 0.133 kPa) to (58.8 +/- 7.7) mm Hg, P < 0.001], and the ratio of the right
      ventricular systolic pressure to systemic systolic pressure decreased by 44%
      [from (1.6 +/- 0.2) to (0.9 +/- 0.1), P < 0.001]. The right ventricular
      angiography showed that the pulmonary valves were opened. The ratio of the
      balloons to annulus were (1.1 +/- 0.1) (the maximal balloon size range from 6 to
      12 mm). The procedure lasted for a mean of (127.5 +/- 32.6) minutes. The duration
      of fluoroscopy was (25.2 +/- 7.2) minutes. Complications occurred in 4 patients
      (30%). Hemopericardium occurred in 2 patients, hypoxia in 1 patient and
      supraventricular tachycardia in 1 patient. One (8%) patient died. The follow-up
      periods were (7.2 +/- 6.4) months. Three patients had moderate to severe residual
      pulmonary stenosis. One of them underwent a second balloon dilation at 3 months
      of follow-up. The other two were waiting for the second dilation. Nine patients
      had mild to moderate residual pulmonary stenosis. All patients had mild pulmonary
      regurgitation. Ductus arteriosus was naturally closured in 11 patients, and
      nearly closured in 1 patient. CONCLUSIONS: Transcatheter intervention for
      critical pulmonary stenosis and atresia with intact ventricular septum in
      neonates is safe and effective. Some patients may require repeat balloon
      valvuloplasty.

PMID- 19099907
TI  - [Outcome of 24 children with myeloid leukemia who received allogeneic stem cell
      transplantation].

PMID- 19099908
TI  - [Clinical significance of serum interleukin-25 in children with asthma].

PMID- 19099909
TI  - [Effect of ligustrazine on expression of RhoA mRNA, ROCK-II protein in the lung
      and airway inflammation of allergic asthma model mice].

PMID- 19099910
TI  - [Clinical features of 414 childhood cases with infectious mononucleosis at
      different age groups].

PMID- 19099911
TI  - [Mycophenolate mofetil therapy for infant with steroid-resistant nephrotic
      syndrome].

PMID- 19099912
TI  - [Two cases with recurrent enlarged parotid gland].

PMID- 19099913
TI  - [Cerebral Sparganosis mansoni: a case report].

PMID- 19099914
TI  - [Ceftriaxone-associated pseudolithiasis in children].

PMID- 19099915
TI  - [Summary of the 13th national conference of pediatric hematology].

PMID- 19099916
TI  - [It's time for hybrid].

PMID- 19099917
TI  - [Pulmonary function testing in Chinese patients with pulmonary arterial
      hypertension].
AB  - OBJECTIVE: To determine the diagnostic value of pulmonary function testing in
      Chinese patients with known pulmonary arterial hypertension (PAH) without history
      of lung/heart valve diseases. METHODS: Pulmonary function testing was performed
      in 41 PAH patients diagnosed by right heart catheterization and in 17 healthy
      controls. RESULTS: Normal pulmonary function testing results were found in 5 PAH
      patients (12.2%). Total lung capacity, vital capacity and FEV1 were significantly
      decreased in PAH patients [(80.27 +/- 11.46)% vs. (94.24 +/- 6.82)%; (79.09 +/-
      14.89)% vs. (97.35 +/- 9.51)%; (75.40 +/- 16.58)% vs. (95.12 +/- 12.01)%,
      respectively, all P < 0.001], the ratio of residual volume/total lung capacity
      was significantly increased [(117.67 +/- 25.73)% vs. (93.39 +/- 10.87)%, P <
      0.001]; FEV1/FVC and maximal expiratory flow of 25% to 75% tended to be lower (
      6.0% and -19.4%, P = 0.21 and 0.09) while DLCO and DLCO/VA were significantly
      decreased by 36.6% and 29.8% (P < 0.001) compared with healthy controls.
      CONCLUSIONS: Increased peripheral airway obstruction and normal lung resistance
      were found in these PAH patients. Normal pulmonary function testing results could
      not rule out the diagnosis of PAH.

PMID- 19099918
TI  - [Value of radionuclide lung scintigraphy in the diagnosis and quantitative
      analysis of chronic thromboembolic pulmonary hypertension].
AB  - OBJECTIVE: This study was to assess the reliability of perfusion/ventilation
      (Q/V) lung scintigraphy in the diagnosis and quantitative analysis of chronic
      thromboembolic pulmonary hypertension (CTEPH). METHODS: A total of 78 in-patients
      with pulmonary hypertension who had no history of congenital heart disease,
      valvular disease and acute pulmonary embolism were included in this study. All
      patients underwent Q/V scintigraphy for detecting CTEPH. The sensitivity,
      specificity and accuracy of Q/V scintigraphy were defined by comparing with the
      results of pulmonary angiography. Percentage of Perfusion Defect score (PPDs%)
      was calculated in patients with CTEPH confirmed by pulmonary angiography. The
      correlations between PPDs% and mPAP, PPDs% and SPAP were analyzed. RESULTS: The
      sensitivity, specificity and accuracy of a high-probability Q/V scintigraphy
      interpretation were 96.0%, 81.1% and 86.9%, respectively, compared with 100%,
      69.8% and 79.5% for the combination of high- and intermediate- probability Q/V
      scintigraphy interpretation. PPDs% was significantly correlated with mPAP and
      SPAP (r = 0.538 for mPAP, P < 0.01 and r = 0.456 for SPAP, P < 0.05). CONCLUSION:
      Perfusion/ventilation lung scintigraphy is a valuable technique for diagnosis and
      quantitative analysis of CTEPH.

PMID- 19099919
TI  - [Prognosis of patients with chronic thromboembolic pulmonary hypertension
      receiving conservative or operative treatments according to a new clinical
      classification scheme].
AB  - OBJECTIVE: To compare the efficacy of conservative or pulmonary
      thromboendarterectomy (PTE) therapy for chronic thromboembolic pulmonary
      hypertension (CTEPH) patients according to a new clinical classification scheme.
      METHODS: This retrospective study analyzed 63 cases of CTEPH admitted to our
      hospital from February 1995 to October 2007 and 45 cases were treated surgically
      (Group A) and 18 cases received conservative therapy (Group B). Results were
      analyzed using Fisher exact test and t test according to San Diego medical center
      quartering classification scheme and Anzhen Hospital modified bifurcate
      classification scheme. RESULTS: There were 6 operational deaths in Group A and 2
      deaths during hospital stay in Group B. During follow-ups (mean 3.6 +/- 2.5
      years), there were 4 deaths in Group A and 9 deaths in Group B. the totality
      survival rate is significantly higher in Group A than that in Group B (P < 0.05).
      For patients with San Diego Type I CTEPH, survival rate was significantly higher
      in Group A compared with Group B (P = 0.009) and was similar for patients with
      type II and III and IV CTEPH between the two groups (P = 0.338, 0.455, 0.800).
      Survival rate was significantly higher in Group A than that in Group B for
      patients with Anzhen central type CTEPH (P = 0.009), but was similar between the
      two groups for patients with Anzhen peripheral type CTEPH (P = 0.125). The Kaplan
      Meier survival curve 5 years survival rate in the Group A was (91.7 +/- 8.0)% for
      Anzhen central type and (76.0 +/- 8.5)% for Anzhen peripheral type (P = 0.04),
      and the 5 years Kaplan-Meier survival rate in the Group B was (42.9 +/- 18.7)%
      for Anzhen central type and (56.2 +/- 10.8)% for Anzhen peripheral type (P =
      0.851). CONCLUSION: Anzhen Hospital modified bifurcate classification scheme is a
      simple and effective classification to predict the prognosis and choose treatment
      method of CTEPH.

PMID- 19099920
TI  - [Increased autoantibody production against AT(1)-receptors and alpha(1)
      adrenergic receptors in hypertensive patients].
AB  - OBJECTIVE: To observe autoantibodies production against AT(1)-receptors and
      alpha(1)-adrenergic receptors and association to risk factors, such as sex, age,
      family history, course of hypertension and other cardiovascular diseases in
      hypertensive patients. METHODS: A total of 690 patients with essential
      hypertension admitted to our hospital were selected and autoantibodies against
      AT(1)-receptors and alpha(1)-adrenergic receptors were detected by ELISA.
      Multiple logistic regression analysis was performed based on obtained data.
      RESULTS: Positive rates for antibody against AT(1)-receptors and alpha(1)
      adrenergic receptors were 47.1% (325/690) and 36.4% (251/690) respectively in
      this group of patients. Duration of hypertension history was significantly longer
      in the antibody against AT(1)-receptors and alpha(1)-adrenergic receptors
      positive groups [(9.3 +/- 11.0) year, (9.9 +/- 11.1) year] compared to the
      negative groups [(7.3 +/- 9.3) year, (7.2 +/- 9.5) year, all P < 0.01]. The ratio
      of family history with hypertension was also significantly higher in antibody
      positive groups than negative ones (47.69% vs 39.18%, P < 0.01). Regression
      analysis demonstrated that 5 risk factors were related to positive production of
      autoantibody against AT(1)-receptors including female gender, age, family
      history, duration of hypertension history and diabetes. However, just age, family
      history, duration of hypertension history were main factors responsible to the
      production of autoantibody against alpha(1)-adrenergic receptors (all P < 0.05).
      CONCLUSION: The environmental and genetic factors contributed to the autoantibody
      production in patients with essential hypertension.

PMID- 19099921
TI  - [Circadian rhythm of melatonin and blood pressure changes in patients with
      essential hypertension].
AB  - OBJECTIVE: To observe the association between melatonin (MLT) secretion and blood
      pressure changes during 24 hours in hypertensive patients (HPT) with (dipping) or
      without (non-dipping) night time blood pressure reduction. METHODS: The 24-hour
      blood pressure and urine 6-SMT (6-sulfatoxymelatonin, metabolism product of MLT
      in urine) in the daytime and nighttime were measured in normal control subjects
      (n = 20), non-dipping HPT group (n = 32) and dipping HPT group (n = 36). RESULTS:
      As expected, blood pressure reduction during the night was significantly lower in
      non-dipping HPT group compared to control and dipping HPT groups. Nighttime 6-SMT
      was significantly higher than daytime 6-SMT in all groups and nighttime urine 6
      SMT levels and ratio of nighttime/daytime urine 6-SMT levels were significantly
      lower in non-dipping HPT group compared to control and dipping HPT groups (all P
      < 0.01). Moreover, ratio of nighttime/daytime urine 6-SMT levels are positively
      correlated blood pressure reduction during nighttime (P < 0.05) in all groups.
      CONCLUSIONS: Circadian rhythm of MLT secretion is maintained but nighttime MLT
      secretion was significantly reduced and related to disorders of circadian rhythm
      of blood pressure in non-dipping HPT group.

PMID- 19099922
TI  - [Geographical characteristics of single nucleotide polymorphism of candidate
      genes associated with coronary artery disease in Chinese Han population].
AB  - OBJECTIVE: To investigate the geographical characteristics of single nucleotide
      polymorphism (SNP) of candidate genes associated with coronary artery disease in
      Chinese Han population. METHODS: Study population were Chinese Han nationality
      recruited from Xi'an, Shiyan and Ningbo districts. Patients with coronary artery
      disease were defined by coronary angiography with stenosis >or= 50% and control
      subjects with stenosis < 10%, respectively. The DNA was extracted from peripheral
      white blood cell by approach comprised proteinase K digestion, phenol and
      chloroform extraction as well as isopropanol precipitation. The SNP of ATP
      binding cassette transporter (ABCA1)-G596A, cholesteryl ester transfer protein
      (CETP)-Taq1B, Lipoprotein lipase (LPL)-Hind III and LPL-Pvu II were genotyped by
      PCR-RFLPs, and verified by gene sequencing. RESULTS: A Total of 615 patients
      undertaken coronary angiography were recruited from cardiac center in Xi'an
      (220), Ningbo (209) and Shiyan district (186), China (mean age 60 +/- 10 years,
      75.9% males). Diabetes mellitus was more prevalent in Xi'an Cohort population
      than Shiyan and Ningbo cohort (P < 0.01). Plasma total cholesterol, LDL
      cholesterol and triglyceride levels in Xi'an Cohort population were significantly
      higher, and HDL-C siginificantly lower than in Shiyan and Ningbo cohort
      population [HDL-C: (1.17 +/- 0.48) mmol/L vs. (1.25 +/- 0.33) mmol/L and (1.29 +/
      0.44) mmol/L, P < 0.05]. Distribution differences for ABCA1-G596A and CETP-Taq1B
      genotypes were found in Xi'an Cohort population compared to Ningbo and Shiyan
      cohorts (for ABCA1, Xi'an: 0.24, 0.53, 0.23 and Shiyan: 0.17, 0.62, 0.21 and
      Ningbo: 0.34, 0.37, 0.29, for GG, AG, AA, respectively, P < 0.01; and for CETP,
      Xi'an: 0.29, 0.54, 0.17 and Shiyan: 0.38, 0.40, 0.22 and Ningbo: 0.39, 0.49, 0.12
      for B1B1, B1B2, B2B2, respectively, P < 0.01), but not for LPL variants. ABCA1
      G596A variant predicted HDL-C [Xi'an: (1.2 +/- 0.3) mmol/L, (1.3 +/- 0.2) mmol/L
      and (1.4 +/- 0.4) mmol/L, P = 0.01; Shiyan: (1.1 +/- 0.4) mmol/L: (1.2 +/- 0.3)
      mmol/L and (1.3 +/- 0.4) mmol/L, P = 0.03; Ningbo, (1.2 +/- 0.3) mmol/L, (1.3 +/-
      0.4) mmol/L and (1.4 +/- 0.3) mmol/L, across GG, GA to AA genotype, respectively,
      P = 0.01] and TG levels [Xi'an: (2.4 +/- 1.3) mmol/L, (1.9 +/- 0.9) mmol/L and
      (1.6 +/- 0.8) mmol/L, P < 0.01; Shiyan: (2.1 +/- 1.0) mmol/L, (1.9 +/- 0.8)
      mmol/L and (1.8 +/- 0.7) mmol/L, P = 0.03; Ningbo: (1.9 +/- 1.1) mmol/L, (1.8 +/-
      0.9) mmol/L and (1.6 +/- 0.7) mmol/L, across GG, GA to AA genotype, P = 0.05]
      with dose-dependent relationship. LPL-Hind III (+) carriers had higher
      triglycerides in three cohort population [Xi'an: (2.2 +/- 1.0) mmol/L, (1.8 +/-
      0.9) mmol/L, (1.6 +/- 0.7) mmol/L, P = 0.01; Shiyan: (2.1 +/- 0.7) mmol/L, (1.9
      +/- 1.0) mmol/L, (1.7 +/- 0.6) mmol/L, P = 0.01; Ningbo: (1.8 +/- 1.0) mmol/L,
      (1.6 +/- 0.6) mmol/L and (1.4 +/- 0.5) mmol/L, for +/+, +/- and -/- genotypes,
      respectively, P = 0.001]. SNP of CETP-Taq1B, LPL-Hind III and LPL-Pvu II
      predicted HDL-C and/or TG levels in different cohort population with different
      manners. All these SNP were not significantly associated with the development of
      coronary artery disease (all P > 0.05). CONCLUSION: A geographical heterogeneity
      of environmental and genetic risk factors related to the development of coronary
      artery disease exists in Chinese Han population. Irrespective of the different
      geographical cohort of Chinese Han population, the SNP of candidate genes can
      partly predict the differences in risk-related plasma HDL-C and/or TG levels
      rather than angiographic coronary artery disease.

PMID- 19099925
TI  - [Effects of trimetazidine on myocardial metabolism evaluated by PET-CT in
      patients with ischemic cardiomyopathy].
AB  - OBJECTIVE: Trimetazidine (TZM) has been shown to have anti-ischemia properties by
      optimizing ischemic myocardium metabolism. We evaluated the effect of TZM on
      myocardial metabolism with Positron Emission Computed Tomography (PET-CT) in
      patients with ischemic cardiomyopathy. METHODS: TZM (60 mg/d, n = 15) or placebo
      (n = 15) was randomly applied to ischemic cardiomyopathy patients on top of
      conventional therapy for 12 months. Color Doppler Flow Imaging (CDFI), (18)F-FDP
      PET-CT imaging and (99m)Tc-MIBI gated single photon emission computerized
      tomography (SPECT) imaging were performed at study begin and after 12 months.
      LVEF with CDFI, summed rest scores (SRS) with SPECT and standard uptake value
      (SUV) with PET-CT of the segments which were perfusion-metabolism matched and
      decreased were determined respectively. RESULTS: After 12 months, LVEF of the
      therapy group was increased from (37.9 +/- 5.0)% to (42.3 +/- 10.4)% (P < 0.05),
      while the control group increased from (37.9 +/- 4.6)% to (40.1 +/- 5.5)% (P >
      0.05); SRSs of the matched segments of the therapy and the control were reduced
      from 3.9 +/- 1.0 to 2.4 +/- 2.3 (P < 0.01) and 4.0 +/- 0.7 to 2.8 +/- 1.8 (P <
      0.05) respectively, while LVEF and SRSs were similar at study begin and after 12
      months between these two groups. SUV of myocardial segments classified as
      myocardial perfusion-metabolism matched was increased from 5.3 +/- 1.5 to 9.8 +/-
      4.7 in the therapy group (P < 0.05) and from 5.4 +/- 1.2 to 6.0 +/- 2.3 (P >
      0.05) in the placebo group, SUV was significantly higher in the therapy group
      than that in placebo group after 12 months (P < 0.05). CONCLUSION: SPECT and
      (18)F-FDG imaging combination could be used to detect the surviving myocardium
      and chronic trimetazidine treatment could increase the glucose metabolism of
      ischemic cardiomyocytes in patients with ischemic cardiomyopathy.

PMID- 19099923
TI  - [Predict value of clinical risk score, thrombolysis in myocardial infarction flow
      grade and combined clinical risk score plus TIMI flow on outcome evaluation of
      patients with acute coronary syndrome].
AB  - OBJECTIVE: To compare the prognostic value of clinical risk score and
      thrombolysis in myocardial infarction (TIMI) flow grade alone or combined on
      outcome of acute coronary syndrome (ACS). METHODS: A total of 206 eligible
      patients [135 males, mean age (67.57 +/- 9.88) years] were enrolled. The primary
      endpoints included cardiac death and non-cardiac death. The secondary endpoints
      included non-fatal stroke, reinfarction, heart failure and recurrent angina.
      Receiver operating characteristic curve (ROC) established by using different
      endpoints and clinical risk score, TIMI flow grade or combined risk scores. The
      prognostic value for different endpoint expressed as the area under the curve
      (AUC). RESULTS: Eleven patients lost during the (11.41 +/- 5.33) months follow up
      and data were available for 195 patients, 8 patients reached the primary
      endpoints, and 17 patients reached the secondary end-points at the end of follow
      up. The AUC was 0.67 (95% CI = 0.557 approximately 0.786), P = 0.006; 0.68 (95%
      CI = 0.557 approximately 0.786), P = 0.004 and 0.730 (95% CI = 0.691
      approximately 0.815), P < 0.001, respectively for clinical risk score, TIMI flow
      grade and the combined risk score respectively. There were no significant
      differences among clinical risk score, TIMI flow grade and combined risk score
      (all P > 0.05) for AUC and for primary end point and the secondary end point.
      CONCLUSION: The result from this study suggests that the efficacy of predicting
      the total events based on clinical risk score, TIMI flow grade and combined risk
      score was similar.

PMID- 19099926
TI  - [Clinical features of coronary artery spasm patients with or without myocardial
      bridge].
AB  - OBJECTIVE: To investigate the clinical features of coronary artery spasm patients
      with or without myocardial bridge and explore the roles of endothelial
      dysfunction in these patients. METHODS: One hundred eighteen patients undergone
      acetylcholine provoking test were divided into myocardial bridge (MB) group (n =
      26) and non-myocardial bridge (NMB) group (n = 92). The results of acetylcholine
      test, treadmill exercise electrocardiography, stress myocardial perfusion
      scintigraphy, plasma level of endothelin-1 and nitric oxide were compared between
      MB group and NMB group. RESULTS: Coronary artery spasm was induced in 21 patients
      in MB group (81%) and 52 patients in NMB group (57%, P < 0.05). Positive
      treadmill electrocardiography was obtained in 19 patients in MB group (73%) and 7
      patients in NMB group (8%, P < 0.001). Ischemic perfusion defect in 20 (77%) and
      9 patients (10%, P < 0.001) and reverse redistribution in 23 (88%) and 68
      patients (74%, P > 0.05). Patients showed different clinical features in MB group
      and NMB group (more short-duration exertional angina and could not be readily
      released by nitroglycerine in MB group while more patients experienced long
      lasting variant angina and symptoms could be readily released by nitroglycerine).
      Plasma endothelin-1 level was significantly higher [(132.1 +/- 6.5) ng/L vs.
      (108.5 +/- 8.2) ng/L, P < 0.01] while nitric oxide was significant lower [(84.7
      +/- 17.5) ng/L vs. (99.8 +/- 18.2) ng/L, P < 0.05] in MB group compared to NMB
      group. CONCLUSION: MB patients were prone to coronary artery spasm partly due to
      endothelial dysfunction. Patients with MB and coronary artery spasm also showed
      classic clinical symptoms and positive stress tests for ischemia.

PMID- 19099927
TI  - [Trauma induced left anterior descending coronary artery dissection and anterior
      wall myocardial infraction in a 21 year-old man].

PMID- 19099928
TI  - [Left ventricular dyssynchrony evaluated by echocardiography in chronic heart
      failure patients with normal and wide QRS duration].
AB  - OBJECTIVE: The aim of the study is to evaluate the left ventricular (LV)
      dyssynchrony in chronic heart failure (HF) patients with normal and wide QRS
      duration. METHODS: Time to peak velocity at peak systolic and early diastolic
      phase (Ts and Te) were determined in 12 segments of LV by echocardiography (GE
      Vivid 7) in 54 HF patients (28 with wide and 26 with normal QRS duration) and 15
      normal controls to evaluate LV systolic and diastolic dyssynchrony. The risk
      factors related to LV dyssynchrony were also evaluated. RESULTS: LV end systolic
      and diastolic volumes were significantly larger and 12 segmental mean Ts and
      maximal Te difference (Te-diff) were significantly higher in HF patients with
      wide QRS duration than HF patients with normal QRS duration. Using mean Ts >or=
      182 ms as the cut-off value, systolic dyssynchrony was present in 46% HF patients
      with normal QRS and 71% HF patients with wide QRS. Using Te-diff >or= 79 ms as
      the cut-off value, diastolic dyssynchrony was seen in 58% HF patients with normal
      QRS and 89% HF patients with wide QRS. Combined systolic and diastolic
      dyssynchrony was seen in 31% HF patients with normal QRS and in 64% HF patients
      with wide QRS. Systolic dyssynchrony was significantly correlated to LV end
      systolic volume and diastolic dyssynchrony was correlated to end diastolic
      volume. CONCLUSION: Percentage of LV dyssynchrony was significantly higher in HF
      patients with wide QRS, especially in HF patients with increased LV end systolic
      and diastolic volume.

PMID- 19099931
TI  - [Myocardial toll like receptor 4 expression in a rat model of myocardial ischemia
      reperfusion injury].
AB  - OBJECTIVE: To explore the role of TLR4 in myocardial ischemia reperfusion injury
      (MI/RI) by observing the dynamic TLR4 expression changes at mRNA and protein
      levels early after myocardial ischemia reperfusion. METHODS: Male SD rats were
      randomly divided into Sham and IR group and the rats were killed according to
      different reperfusion time (0, 0.5, 1, 2, 4 and 8 hours). Myocardial changes
      under light microscope and transmission electronic microscope were observed. TLR4
      expressions at protein and mRNA levels were detected by immunohistochemistry and
      realtime RT-PCR respectively. Myocardial TNF-alpha was determined by ELISA.
      RESULTS: (1) Myocardial injury was observed in IR but not in Sham group and
      histopathological and ultrastructural changes in IR group remained unchanged up
      to 8 hours after reperfusion. (2) Positive TLR4 protein staining was visualized
      in both Sham and IR groups and significantly increased and peaked at 1 hour of
      reperfusion in IR group. (3) Compared to Sham group, TLR4 mRNA level was
      upregulated in myocardium in IR group and peaked at 1 hour of reperfusion. (4)
      Concentration of TNF-alpha in IR group was significantly higher than that of Sham
      group at corresponding time points (all P < 0.05), and myocardial TLR4 mRNA level
      correlated positively with myocardial TNF-alpha (r = 0.728, P < 0.01).
      CONCLUSION: Expression of TLR4 in myocardium during early after myocardial
      ischemia reperfusion was upregulated and actived TLR4 might play an important
      role in MI/RI through promoting myocardial TNF-alpha excretion.

PMID- 19099930
TI  - [Association between lysosomal cysteine protease cathepsin's activation and left
      ventricular function and remodeling in hypertensive heart failure rats].
AB  - OBJECTIVE: To observe myocardial cathepsin (Cat) S expression and activity in
      hypertensive heart failure rats. METHODS: The expression and activity of Cat S
      were determined in the left ventricular (LV) myocardium (LVM) of Dahl salt
      sensitive rats fed either a high-salt (HS, 8%) or low-salt (LS, 0, 3%, controls)
      diet starting at age 7 weeks for 12 weeks (hypertrophy model, H-LVH) or 19 weeks
      (heart failure model, H-HF). Age-matched rats served as controls and human
      normal, hypertensive and heart failure myocardial specimen were also examined for
      changes on the expression and activity of Cat S. RESULTS: Reverse transcription
      and real-time polymerase chain reaction analysis revealed significantly
      upregulated Cat S mRNA in rats with H-HF than in rats with H-LVH or in control
      rats and Cat S mRNA expression is negatively correlated with LVEF (r = -0.88, P <
      0.05). In situ and immunohistochemistry examinations showed that Cat S was
      localized predominantly in cardiac myocytes (CMCs) and coronary vascular smooth
      muscle cells (SMC). Elastic lamina fragmentations and Cat S-dependent elastolytic
      activity were significantly increased in H-HF-rats. The expression of interleukin
      1 beta was also increased in the LVM of H-HF rats, and this cytokine was found to
      increase the Cat S protein expression in culture neonatal CMCs. Similar results
      were revealed in human myocardial specimens. CONCLUSION: Elastolytic Cat S might
      play an important role in the pathogenesis of myocardial remodeling and heart
      failure and Cat S might serve as a novel therapeutic target in preventing or
      reversing hypertension induced LV remodeling and heart failure.

PMID- 19099932
TI  - [Effect of fibrinogen, fibrin and fibrin (ogen) degradation products on the
      tissue plasminogen activator and plasminogen activator inhibitor-1 expressions of
      vascular endothelial cells in coculture system].
AB  - OBJECTIVE: To investigate the effect of fibrinogen (Fg), fibrin (Fb) and fibrin
      (ogen) degradation products (FDPs) on tissue plasminogen activator (tPA) and
      plasminogen activator inhibitor-1 (PAI-1) expressions of human umbilical vein
      endothelial cells (HUVECs) in coculture system. METHODS: Fg, Fb and FDPs at
      various concentrations (0, 0.5, 1.5, 3.0, 4.5 and 6.0 g/L) were added to the
      transwell coculture system of HUVECs and smooth muscle cells (SMCs) for 24 hours.
      The expressions of tPA and PAI-1 at mRNA level were examined by RT-PCR and tPA
      and PAI-1 protein and activity were detected by ELISA and substrate chromogenic
      assays. RESULTS: tPA expression was not affected by Fg. Fg at concentrations
      between 3.0 - 4.5 g/L significantly enhanced the mRNA expression, protein content
      and activity of PAI-1, while expression of PAI-1 was significantly inhibited by
      Fg at concentration of 6.0 g/L. Fb at concentrations between 3.0 - 4.5 g/L
      significantly up-regulated mRNA expression, increased protein content and down
      regulated activity of tPA. Fb (1.5 - 4.5 g/L) also enhanced the mRNA expression,
      increased protein content and activity of PAI-1. FDPs at concentrations 3.0 - 6.0
      g/L down-regulated the expression of tPA and FDPs at concentrations 1.5 - 6.0 g/L
      significantly enhanced PAI-1 mRNA expression. CONCLUSION: Fg, Fb and FDPs play
      important roles in the pathogenesis of atherosclerosis by modulating the
      expression of tPA and PAI-1 of endothelial and SMCs.

PMID- 19099933
TI  - [Effects of carvedilol and metoprolol on cardiac fibrosis in rats with
      experimental myocardial infarction].
AB  - OBJECTIVE: To investigate the effects of carvedilol and metoprolol on cardiac
      fibrosis in rats with experimental myocardial infarction (MI). METHODS: MI was
      induced in male Sprague-Dawley rats by ligating the left coronary artery. Rats
      randomly received saline, carvedilol (10 mg.kg(-1).d(-1)) or metoprolol (20
      mg.kg(-1).d(-1)) beginning at 4 weeks post MI for 8 weeks per gavage. Sham
      operated rats serve as control. Collagen perivascular circumferential collagen
      area (PCVA), peri-coronary circumferential collagen area (VLCA) and interstitial
      collagen volume fraction (ICVF) as well as myocardial hydroxyproline content were
      determined after hemodynamic measurements at the study end. RESULTS: LVEDP were
      significantly lower and +/- dp/dt significantly higher in carvedilol and
      metoprolol treated MI rats than that in saline treated MI rats. Myocardial
      hydroxyproline, PCVA/VLCA ratio and ICVF were significantly reduced in
      metoprolol, more significantly reduced in carvedilol treated MI rats compared to
      saline treated MI rats (all P < 0.05). CONCLUSION: Metoprolol and carvedilol
      could decrease the concentration of hydroxyproline and ICVF in MI rats.

PMID- 19099934
TI  - [Effects of pravastatin on myocardial connexin 43, IFN-gamma and IL-10
      expressions in a murine model of viral myocarditis induced by Coxsackievirus B3].
AB  - OBJECTIVE: To observe the effects of pravastatin on myocardial connexin 43
      (Cx43), IFN-gamma and IL-10 expressions in a murine model of viral myocarditis
      (VMC) induced by Coxsackievirus B3. METHODS: Four-week-old male Balb/c mice were
      inoculated intraperitoneally with Coxsackievirus B3 and then randomly received
      saline (group A, n = 12), low dose pravastatin (40 mg.kg(-1).d(-1), group B, n =
      12) and high dose pravastatin (80 mg.kg(-1).d(-1), group C, n = 12) for 14 days.
      Another group of mice were injected with Eagle's solution and treated with saline
      (group D, n = 12) or high dose pravastatin (80 mg.kg(-1).d(-1), group E, n = 12).
      After 14 days treatments, serum IFN-gamma, IL-10 were assayed using ELISA,
      myocardium IFN-gamma, IL-10 and Cx43 mRNA levels were measured by real-time PCR,
      myocardium expression of Cx43 was also determined by immunohistochemistry
      staining method on cardiac myocytes. RESULTS: Pravastatin dose-dependently
      upregulated Cx43 proteins on membrane of myocardial cells (group A: 0.16 +/-
      0.06, group B: 4.55 +/- 0.73 and group C: 5.21 +/- 0.42, P < 0.01 vs. group A)
      and Cx43 mRNA expression (group A: 1.000 +/- 0.127, group B: 1.320 +/- 0.096,
      group C: 1.550 +/- 0.126, P < 0.05 vs. group A), IL-10 mRNA expression (group A:
      1.000 +/- 0.031, group B: 1.810 +/- 0.029, group C: 2.140 +/- 0.032, P < 0.05 vs.
      group A) while down-regulated IFN-gamma mRNA (group A: 1.000 +/- 0.061, group B:
      0.603 +/- 0.063, group C: 0.333 +/- 0.071, P < 0.01 vs. group A). Serum IFN
      gamma, IL-10 concentrations changed in the same direction as myocardial mRNA
      levels of IFN-gamma, IL-10 post pravastatin treatments. CONCLUSION: Pravastatin
      treatments upregulated expressions of Cx43 at mRNA and protein levels and
      improved the INF-gamma/IL-10 balance which might be the working mechanisms for
      pravastatin-mediated anti-VMC and anti-arrhythmia effects in this VMC model.

PMID- 19099935
TI  - [Repetitive monomorphic ventricular tachycardia arising from left His-Purkinje
      system].

PMID- 19099937
TI  - [Research progress of diagnosis in heart transplant associated coronary artery
      disease].

PMID- 19099938
TI  - [Recent progress on the effect of GATA-4 on the cardiovascular system].

PMID- 19099942
TI  - [Current status and challenges of percutaneous coronary intervention for chronic
      total occlusions].

PMID- 19099943
TI  - [Comparison of DK crush with classical crush technique with drug-eluting stents
      for the treatment of coronary bifurcation lesions from DKCRUSH-1 study].
AB  - OBJECTIVE: To determine independent factors correlated with clinical effects of
      DK crush and classical crush technique with drug-eluting stents on bifurcation
      lesions. METHODS: 311 patients with bifurcation lesions were randomized to
      classical (C, n = 156) or double kissing (DK) crush (n = 155) stent implantation
      group. The primary endpoints included major adverse cardiac events (MACE).
      RESULTS: Final kissing balloon inflation (FKBI) success rate was 76% in C and
      100% in DK groups (P < 0.001). DK crush procedure was characterized by lower
      unsatisfactory FKBI rate (27.6% vs.6.3%, P < 0.01). Clinical follow-up was
      available in 100% and angiographic follow-up in 82% patients. The overall
      restenosis rate was 32.3% in C and 20.3% in DK groups (P = 0.01), respectively.
      Cumulative 8-month MACE was 35.9% in without-FKBI and 19.7% in with-FKBI sub
      groups, and 11.4% in DK group (P = 0.02). The incidence of stent thrombosis was
      3.2% in C group (5.1% without vs. 1.7% with FKBI) and 1.3% in DK group (P >
      0.05). The predictive factors of MACE included minimal side branch stent lumen
      diameter and lack of DK crush technique. CONCLUSION: DK crush technique is an
      alternative of double stenting techniques in terms of improvement of restenosis
      and clinical outcomes.

PMID- 19099944
TI  - [Long-term efficacy of sirolimus-eluting stents (Cypher) versus bare metal stents
      for patients with ST-segment elevation myocardial infarction].
AB  - OBJECTIVE: To observe the safety and long-term efficacy of Cypher stent versus
      bare metal stents (BMS) in patients with STEMI. METHODS: From Dec 2002 to Mar
      2005, clinical and angiographic data of 407 consecutive patients with STEMI
      treated with Cypher stent (n = 131) or BMS (n = 276) were analyzed and followed
      up for a mean period of 28.7 +/- 11.7 months. Major adverse cardiac events
      (MACE): death, nonfatal reinfarction and target lesion revascularization (TLR)
      during follow up was compared between two groups. RESULTS: Compared with the BMS
      group, diameter of vessels were significantly smaller (3.0mm vs. 3.2mm, P =
      0.00), the incidence of MACE (6.1% vs. 12.7%, P = 0.04) and total mortality (1.5%
      vs. 6.9%, P = 0.02) were significantly lower in the Cypher group. The relative
      risk for MACE in Cypher group was 0.61 (P < 0.05), while there was no significant
      difference in the rate of stent thrombosis, rate of target lesion
      revascularization and restenosis. CONCLUSION: Utilization of Cypher in the
      setting of primary PCI for STEMI was safe and improved the long-term clinical
      outcomes compared to BMS.

PMID- 19099946
TI  - [Emergency treatment succeeded in acute myocardial infarction with acute
      pancreatitis and multi-organ failure: a case report].

PMID- 19099945
TI  - [Effects of treating ostial left anterior descending artery stenosis by drug
      eluting stents via precisely positioning or crossing over into left main stem].
AB  - OBJECTIVE: To compare the effect of treating ostial left anterior descending
      artery (LAD) stenosis using drug-eluting stents (DES) by precisely positioning
      versus crossing over into left main (LM) technique. METHODS: From April 2004 to
      May 2006, DES implantations in 224 consecutive patients with ostial LAD lesions
      were performed by precisely positioning in 161 patients (P group) and crossing
      over into LM in 63 patients (C group). Clinical and angiographic follow-up was
      performed at 7 months post DES implantations. RESULTS: Relevant vessel diameter
      (RVD) was significantly larger (3.44 +/- 0.52 mm vs. 3.17 +/- 0.40 mm, P = 0.039)
      and LM/LAD diameter ratio was significantly lower (1.16 +/- 0.07 vs. 1.28 +/-
      0.05, P = 0.000) in C group compared that in P group. Stent (3.53 +/- 0.31 mm vs.
      3.16 +/- 0.29 mm, P = 0.035) and postdilatation balloon (3.59 +/- 0.65 mm vs.
      3.24 +/- 0.32 mm, P = 0.035) diameter were significantly larger and
      postdilatation (94.1% vs. 29.5%, P = 0.000) and kissing balloon (47.1% vs. 15.2%,
      P = 0.000) rates were significantly higher in P group than that in C group. Both
      groups achieved 100% procedure success rate. Major adverse cardiac events (MACE)
      rate (4.3% vs. 1.6%, P = 0.447), death (0 vs. 0, P = 1.000), AMI (1, 2% vs. 1.6%,
      P = 1.000) and target vessel revascularization (TVR) rate (3.1% vs. 0%, P =
      0.325) were similar between the 2 groups. One patient in P group developed
      subacute in-stent thrombosis. Follow-up angiography at 7 months showed that in
      stent (0 vs.7.7%, P = 0.316) and in-segment restenosis rate (3.8%vs. 10.8%, P =
      0.431) tended to be lower while in-stent (0.12 +/- 0.08 mm vs. 0.59 +/- 0.37 mm,
      P = 0.000) and in-segment (0.17 +/- 0.09 mm vs. 0.64 +/- 0.49 mm, P = 0.000) late
      loss were significantly lower in C group compared with P group. CONCLUSION:
      Compared with precisely positioning technique, crossing over into LM technique
      was more feasible and tended to reduce restenosis rate for ostial LAD lesions
      treated with DES.

PMID- 19099947
TI  - [Association between metabolic syndrome and the 10 years mortality of cerebro
      cardiovascular diseases in the senile population].
AB  - OBJECTIVE: To assess the prevalence of metabolic syndrome (MS) and its
      association with mortality of cerebro-cardiovascular diseases in senile
      population. METHODS: Data were collected from 1926 people aged 60 and over, who
      took part in routine health examination in our hospital from 1996 to 1997. All
      subjects were followed up for 10 years. MS was diagnosed by using the definition
      recommended by Chinese Diabetic Society in 2004. Cox-proportional hazards models
      were used in survival analyses and to calculate the relative risk (RR) of cerebro
      cardiovascular diseases mortality. RESULTS: The prevalence of MS was 25.03% (n =
      482, Group 2) in this population. The 10 year mortality of cerebro-cardiovascular
      diseases was significantly higher (6.82/1000-person year vs. 2.55/1000-person
      year, P < 0.05) and the cumulative survival rate was significantly lower
      (92.46%vs. 97.14%, P < 0.05) in group 2 compared that in group 1 (non-MS, n =
      1444). Compared with group 1, RR of cerebro-cardiovascular diseases mortality was
      2.52 (95% CI 1.367 - 4.661, P < 0.05) in group 2. CONCLUSION: There was a high
      prevalence of MS in the senile population and MS was associated with higher 10
      years mortality of cerebro-cardiovascular diseases.

PMID- 19099948
TI  - [Quality of life five years after coronary artery bypass grafting].
AB  - OBJECTIVE: The quality of life (QOL) 5 years after coronary artery bypass
      grafting (CABG) was evaluated by NHP, SAQ and DASI questionnaires. METHODS: NHP,
      SAQ and DASI questionnaires were mailed to 287 patients who received CABG in our
      department between Jan 2001 and Jan 2002. The reliability and construct validity
      of the questionnaires and the influence factor of QOL were analyzed. RESULTS: Two
      hundred and seventy-three patients (95%) responded to the questionnaires. The
      reliability of three questionnaires about QOL was 0.81, 0.75 and 0.78,
      respectively. QOL at 5 years post CABG was significantly better in CCS I/II
      patients than CCS III/IV patients' according to SAQ. Exertional scale and disease
      perception scale according to SAQ, social isolation and physical abilities to NHP
      also significantly related to QOL 5 years post CABG. CONCLUSIONS: All 3
      questionnaires had high reliability and statistical validity for evaluating QOL.
      CCS angina degree affect the quality of life in patients 5 years post CABG.

PMID- 19099949
TI  - [Incidence of metabolic disorders in patients with essential hypertension and
      patients with primary aldosteronism].
AB  - OBJECTIVE: To compare the incidence of metabolic disorders (MS) in patients with
      primary aldosteronism (PA) and essential hypertension (EH). METHODS: MS
      prevalence was observed in 200 EH patients (male 104) and 220 PA patients (male
      117) hospitalized to our hospital from August 2005 to March 2007. RESULTS: (1)
      The prevalence of MS in PA group was significantly higher than that of EH group
      (47.3% vs. 31.5%, P = 0.009). (2) Blood pressure was significantly higher in PA
      group than that of EH [SBP: (150.67 +/- 15.45) mm Hg vs. (145.69 +/- 17.13) mm
      Hg, P = 0.042; DBP: (93.03 +/- 10.51) mm Hg vs. (85.83 +/- 14.44) mm Hg, P =
      0.037]. (3) Incidences of abdominal obesity (86.8% vs. 78.5%, P = 0.024) and
      insulin resistance (insulin sensitivity index: 42.42 +/- 16.11 vs. 49.58 +/-
      22.43, P = 0.008) were significantly higher in PA group than in EH group.
      CONCLUSION: The prevalence of MS in hospitalized PA patients was significantly
      higher than that of EH patients characterized by prevalent abdominal obesity,
      insulin resistant and severe hypertension.

PMID- 19099950
TI  - [Endovascular repair for patients with DeBakey III aortic dissection].
AB  - OBJECTIVE: To investigate the clinical therapeutic effects of endovascular repair
      for patients with DeBakey III aortic dissection. METHODS: From December 2002 to
      June 2007, endovascular TALENT stent-graft exclusion was performed in 75 (65
      males, mean age 54.4 +/- 12.6 years) patients with DeBakey III aortic dissection
      (1 young woman due to Ehlers-Danlos syndrome, 2 young men due to primary
      aldosteronism and trauma respectively). All patients were diagnosed by contrast
      enhanced computed tomography (CT) or MRI. Stent-grafts were deployed via femoral
      artery to exclude the tear of dissection. Aortic angiography was performed
      immediately after procedure. RESULTS: Eighty-one stent-grafts were installed in
      75 patients successfully without operation related dissection. Endoleakage
      immediately after stent-graft deploying was evidenced in 25 patients and
      disappeared after stent placements (n = 6) or balloon dilation (n = 19). Two
      patients died from aortic rupture within 2 days after procedure. Iliac artery was
      torn in a female patient with Ehlers-Danlos syndrome, this patient developed
      hemorrhagic shock after stent-graft placement and recovered after anti-shock
      treatments and iliac artery replacement with synthetic artery. During the follow
      up of 1 - 24 months, 2 patients (including the woman with Ehlers-Danlos syndrome)
      suddenly died half a year after procedure. The remaining patients were alive and
      well. Repeat CT during follow up showed that reduced lumen size and thrombosis in
      the false lumen. There was no aortic rupture, endoleak and stent migration during
      the follow-up period except descending aortic dissection distal of the stent
      graft in 1 patient 1 year after procedure and the patient were successfully
      treated surgically without complication. CONCLUSIONS: Endovascular repair is a
      safe and effective treatment for patients with DeBakey III aortic dissection,
      suitable for old patients with high risk of surgery. Ehlers-Danlos syndrome
      should be considered in young DeBakey III aortic dissection patients without
      hypertension. Further studies are warranted on endovascular repair therapy for
      artery complication of Ehlers-Danlos syndrome.

PMID- 19099951
TI  - [Association between CYP2C9 and VKORC1 genetic polymorphism and warfarin dose
      requirements].
AB  - OBJECTIVE: To assess the contribution of vitamin K epoxide reductase complex 1
      (VKORC1) and cytochrome P450 2C9 (CYP2C9) genotype, age, body size, height, and
      weight to warfarin dose requirement. METHODS: Blood samples were collected from
      191 patients receiving warfarin therapy. Patients's age, gender, height, and
      weight were registered. PCR-RFLP method was used for the detection of VKORC1
      1639G > A and CYP2C9 genotype. RESULTS: VKORC1-1639G > A genotyping showed that
      159 patients were homozygous AA, 31 were heterozygous GA, and 1 was homozygous GG
      genotype. CYP2C9 genotyping showed that 176 patients were *1/*1, 15 patients were
      heterozygous *1/*3. Patients with VKORC1-1639 (G > A) GG + GA genotype required a
      significantly higher warfarin dose than those with AA genotype [(3.36 +/- 0.97)
      mg/d vs. (1.75 +/- 0.56) mg/d, P < 0.01], and patients with CYP2C9*1/*1 genotype
      also required a higher warfarin dose than those with CYP2C9*1/*3 genotype [(2.06
      +/- 0.83) mg/d vs. (1.55 +/- 1.32) mg/d, P < 0.05]. The multiple linear
      regression model for warfarin dose indicated age, weight and VKORC1 genotype
      could explain the inter-individual variation in dose requirement of 9.3%, 7.4%,
      51.9% patients, respectively; age, weight, CYP2C9 and VKORC1 genotype together
      could explain the inter-individual variation in dose requirement of 64.1%
      patients. CONCLUSION: This study showed that age, weight and VKORC1 and CYP2C9
      polymorphism had significant influences on warfarin dose requirements and should
      be considered on dosing regimens modification to improve the safety of warfarin
      therapy.

PMID- 19099954
TI  - [N-acetylcysteine promoted aging through adjusting expression of cell cycle
      related protein in neonatal SD rat cardiomyocytes].
AB  - OBJECTIVE: To observe the effects of N-acetylcysteine (NAC) on aging in neonatal
      SD rat cardiomyocytes and explore related mechanisms. METHODS: Cultured
      cardiomyocytes were randomized assigned to 6 groups: 1-day, 5-day, 10-day, 1-day
      + NAC (1 mmol/L), 5-day + NAC (1 mmol/L) and 10-day + NAC (1 mmol/L). Flow
      cytometry was used to examine cell cycle. Real-time quantitative PCR and Western
      blot were used to determine mRNA and protein expression of p16INK4a, p21WAF1 and
      Rb gene. beta-galactosidase staining kit was used to investigate beta
      galactosidase activity. RESULTS: Numbers of cardiomyocytes resided in G(0)/G(1)
      phase were significantly higher in the group of 5-day + NAC and 10-day + NAC
      compared with 5-day, 10-day, respectively (P < 0.05). The mRNA and protein
      expression of p16INK4a and p21WAF1 were also significantly higher in the group of
      5-day + NAC and 10-day + NAC compared with 5-day, 10-day, respectively (P < 0.05
      or P < 0.01). The mRNA and protein expression of Rb was significantly lower in
      the group of 5-day + NAC and 10-day + NAC compared with 5-day, 10-day,
      respectively (P < 0.01). beta-galactosidase activity was not affected by NAC in
      the 1-day + NAC group but was significantly higher in 5-day + NAC and 10-day +
      NAC groups compared with the 5-day, 10-day groups (all P < 0.05). CONCLUSION: NAC
      could promote aging through upregulating the expression of p16INK4a and p21WAF1
      and inhibiting Rb phosphorylation in neonatal SD rat cardiomyocytes.

PMID- 19099955
TI  - [Transcatheter pulmonary valve replacement in sheep: 6-month evaluation of self
      expanding valved stents].
AB  - OBJECTIVE: The purpose of this study was to determine the feasibility of
      transcatheter pulmonary valve replacement in sheep up to 6 months post procedure.
      METHODS: Fresh sheep pericardium treated with a 0.6% glutaraldehyde solution for
      36 hours was sutured to a valvular ring and then fixed onto a newly designed
      nitinol self-expandable stent. Thoracotomy was performed in sheep (23.5 +/- 3.1)
      kg under general anesthesia and the device was delivered into the native
      pulmonary valve of the sheep via the anterior wall of right ventricle by catheter
      and fooled for 6 months. RESULTS: One sheep died 4 months after the procedure due
      to in-stent thrombosis. Another 4 animals survived the 6-month observing period.
      Angiographic and hemodynamic measurements confirmed good positioning and function
      of the stents with a competent valve immediately post procedure and 6 months post
      the procedure in surviving animals. CONCLUSION: Implantation of the nitinol self
      expandable stent in the pulmonary valve position by a transcatheter approach is
      feasible and good function of transcatheter implanted memory nitinol valved
      stents was shown after 6 months of implantation in sheep.

PMID- 19099956
TI  - [Effects of mTOR inhibitor rapamycin on Smad 3 protein and collagen type I
      expression in rat myocardial fibroblasts infected with coxsackie virus B 3].
AB  - OBJECTIVE: Mammalian target of rapamycin (mTOR) plays a central role in
      controlling cell proliferation, survival and growth. We investigated the role of
      mTOR signal transduction on viral myocarditis by observing the effect of mTOR
      inhibitor rapamycin on Smad 3 and collagen type I expression in rat myocardial
      fibroblasts infected with coxsackievirus B 3 (CVB 3). METHODS: Primary cultured
      myocardial fibroblasts of SD rats infected with CVB 3 were treated with or
      without rapamycin. The Smad 3 and collagen type I expression of the cells were
      determined by RT-PCR and Western blot. RESULTS: (1) mTOR/beta-actin ratio was
      dose-dependently reduced (1 nmol/L, 0.381 +/- 0.022; 10 nmol/L, 0.282 +/- 0.014;
      100 nmol/L, 0.263 +/- 0.012 vs. control 1.45 +/- 0.04, all P < 0.05 vs. control)
      after 48 hours rapamycin treatments and time-dependently reduced after 10 nmol/L
      rapamycin treatment (24 h, 0.203 +/- 0.021; 48 h, 0.163 +/- 0.022; 72 h, 0.144 +/
      0.013 vs. 0 h, 0.341 +/- 0.022, all P < 0.05 vs.0 h) in CVB 3 infected
      myocardial fibroblasts. (2) Smad 3/beta-actin ratio of myocardial fibroblasts was
      significantly increased in CVB 3 infected cardial fibroblasts and this increase
      could be significantly attenuated by rapamycin (control, 0.63 +/- 0.06; CVB 3,
      1.18 +/- 0.03; CVB 3 + Rapamycin, 0.77 +/- 0.08 by RT-PCR and 0.89 +/- 0.07, 2.27
      +/- 0.13 and 0.131 +/- 0.013 by Western blot). Collagen type I/beta-actin ratio
      was also significantly increased by CVB 3 and this increase could be reversed by
      rapamycin (1.13 +/- 0.06, 1.303 +/- 0.012, 0.82 +/- 0.03 by RT-PCR). CONCLUSION:
      Rapamycin can inhibit the Smad 3 and collagen type I expressions in CVB 3
      infected myocardial fibroblasts suggesting that the mTOR signal pathway may play
      an important role in the pathogenesis of CVB 3 induced myocardial fibrosis.

PMID- 19099957
TI  - [Effects of ischemia postconditioning on ischemia-reperfusion injury and
      reperfusion injury salvage kinase signal transduction pathways in isolated mouse
      hearts].
AB  - OBJECTIVE: To explore the effects of ischemia postconditioning (IPC) on ischemia
      reperfusion (I/R) injury and associated reperfusion injury salvage kinase (RISK)
      signal transduction pathways changes in isolated mouse hearts. METHODS:
      Langendorff perfused C57/BL mouse hearts were divided to 6 groups: (1) control:
      30 min global ischemia and 2 h reperfusion (I/R); (2) IPC with 3 episodes, IPC
      with 3 episodes of 10 s of ischemia and 10 s reperfusion after 30 min ischemia
      and before 2 h reperfusion; (3) IPC with 6 episodes, IPC with six episodes of 10
      s of ischemia and 10 s reperfusion after 30 min ischemia and before 2 h
      reperfusion; (4) delayed IPC, IPC with 3 episodes of 10 s of ischemia and 10 s
      reperfusion after 30 min ischemia and at one minute after reperfusion; (5) IPC +
      ERK1/2 inhibitor PD98059 (10(-5) mol/L for 15 min); (6) I/R + ERK1/2 inhibitor
      PD98059 (10(-5) mol/L for 15 min). The effects of IPC on hemodynamics, coronary
      artery flow, creatine kinase (CK) and lactate dehydrogenase (LDH) release,
      myocardial SOD, MDA, phospho-protein kinase (P-ERK1/2) and phospho-protein kinase
      B (P-Akt) as well as myocardial infarction size were measured. RESULTS: IPC with
      3 episodes and IPC with 6 episodes significantly and equally improved myocardial
      function, increased myocardial SOD, reduced CK and LDH release and myocardial
      infarction size compared with IR group (all P < 0.01) while these parameters were
      similar between I/R hearts and delayed IPC hearts. IPC significantly increased
      myocardial ERK1/2 phosphorylation, PD98059 inhibited the phosphorylation of
      ERK1/2 and abolished the cardioprotective effects induced by IPC. CONCLUSIONS:
      IPC obviously attenuated I/R injury in isolated mouse hearts, the
      cardioprotection of IPC was not enhanced because of increasing of IPC episodes
      and disappeared in delayed IPC. The cardioprotective effects of IPC were mediated
      through ERK1/2-MAPK signal transduction pathway.

PMID- 19099958
TI  - [Epsilon waves seen in a patient with typical electrocardiography pattern of
      Brugada].

PMID- 19099959
TI  - [Role of alkaloid sinomenine in chronic rejection in the rat heart
      transplantation model].
AB  - OBJECTIVE: To evaluate the possible role of alkaloid sinomenine (SIN) on chronic
      rejection in rat heart transplantation model. METHODS: After a brief course of
      cyclosporine A (CsA), DA recipients of PVG hearts were treated with placebo, SIN,
      CsA, or a combination of both drugs. Grafts were analyzed morphometrically and by
      immuno-histochemistry. Expressions of basic fibroblast growth factor (bFGF),
      vascular endothelial growth factor (VEGF), and endothelin 1 (ET-1) were assessed
      by reverse transcription-polymerase chain reaction. RESULTS: Cardiac grafts of
      SIN-treated rats showed a mild degree of vasculopathy compared with untreated
      rats or CsA-treated recipients. Degree of vasculopathy was significantly reduced
      in rats treated with combined SIN and CsA than rats receiving either drug alone.
      Treatment with SIN alone did not affect gene expressions of bFGF, VEGF, and ET-1
      while expressions of bFGF, VEGF, and ET-1 were significantly reduced by combined
      treatment with SIN and CsA. CONCLUSION: These results demonstrated a potential
      value of SIN, in combination with low-dose CsA to attenuate the vasculopathy in
      this rat model of chronic cardiac allograft rejection.

PMID- 19099963
TI  - [Subacute stent thrombosis after drug-eluting stent implantation for treatment of
      bare metal stent associated very late stent thrombosis].

PMID- 19099964
TI  - [Very late angiographic stent thrombosis after sirolimus-eluting stent
      implantation at 54 months].

PMID- 19099965
TI  - [A case of fistula from left and right coronary artery to pulmonary artery].

PMID- 19099967
TI  - [Recent progress on angiotensin III].

PMID- 19099968
TI  - [Study progress between particulate matter and cardiovascular disease].

PMID- 19099970
TI  - [The role of inflammation on atherosclerotic diseases].

PMID- 19099971
TI  - [Matrix metalloproteinase-1 gene -519A/G polymorphism and the risk of coronary
      heart disease in Northern Chinese Han population].
AB  - OBJECTIVE: To investigate the relationship between matrix metalloproteinase (MMP)
      1 gene -519A/G polymorphism and the risk of coronary heart disease (CHD) in
      Northern Chinese Han population. METHODS: A total of 517 patients with CHD and
      380 healthy adults diagnosed by coronary angiography were genotyped by polymerase
      chain reaction-restriction fragment length polymorphism and DNA sequence
      technology for the -519A/G polymorphism in MMP1 gene. RESULTS: (1) The frequency
      of AA genotype was significantly higher in patients with CHD than that in
      controls [67.70% (350/517) vs. 40.26% (153/380), OR = 1.64, P < 0.001, 95%CI:
      1.44 - 1.86]. People carrying A allele had increased risk for CHD (OR = 1.49, P <
      0.001, 95%CI: 1.33 - 1.69). (2) The frequency of AA genotype was higher in
      patients with acute coronary syndrome (ACS) than patients with stable angina
      pectoris [68.81% (278/404) vs. 51.76% (44/85), P < 0.01, 95%CI: 1.04 - 1.27]. The
      A allele carriers were more likely to develop ACS (OR = 1.11, 95%CI: 1.01 - 1.21,
      P < 0.05). CONCLUSION: Our data shows MMP1 gene -519A/G polymorphism is
      associated with the risk of CHD, and A allele carriers are more susceptible for
      CHD in Northern Chinese Han population.

PMID- 19099972
TI  - [Association between inflammatory cytokine CD40 gene polymorphism and risk of
      acute coronary syndrome].
AB  - OBJECTIVE: To investigate the expression levels of CD40, sCD40L, hs-CRP, WBC in
      acute coronary syndrome (ACS) patients and the association between CD40-1C/T
      single nucleotide polymorphism and risk of ACS in Han Chinese, moreover, the
      regulatory effects of IFN-gamma and fluvastatin on the expression of CD40 in
      peripheral blood mononuclear cell (PBMNC) were also observed. METHODS: (1) 160
      ACS patients and 92 control patients diagnosed by coronary angiography were
      recruited. Enzyme linked immunosorbent assay, particle enhanced
      immunoturbidimetric assay, flow cytometry were used to detect the levels of
      soluble CD40L, hs-CRP, and WBC count. (2) The CD40 genotype and allele frequency
      were analyzed by polymerase chain reaction-restriction fragment length
      polymorphism (PCR-RFLP) and DNA sequencing technology. (3) PBMNC were separated
      by density gradient centrifugation heparinized venous blood from 40 ACS patients,
      cultured for 24 h with or without 100 ng/ml IFN-gamma in the absence or present
      of 10 micromol/L fluvastatin. The CD40 expression levels were then detected by
      flow cytometry. RESULTS: Inflammatory cytokine CD40, sCD40L, hs-CRP levels were
      significantly higher in ACS patients than in controls. The CD40-1C allele
      frequency was 0.606 in ACS group and 0.489 in controls, while T allele frequency
      was 0.394 in ACS group and 0.511 in controls. The frequency of CC genotype was
      significantly higher in ACS group than in controls (P < 0.01). C allele carriers
      had significantly higher risk of ACS (OR = 1.608, 95%CI: 1.12 - 2.32, P = 0.011).
      CD40 production increased after 24 h culturing and the CD40 levels were
      significantly higher in subjects with CC genotype than that in subjects with CT
      or TT genotype [CC: (14.78 +/- 4.56) MFI, CT: (11.98 +/- 4.12) MFI, TT: (9.86 +/-
      3.83) MFI, P < 0.05]. IFN-gamma further increased PBMNC CD40 expressions in all
      subjects after culturing for 24 h and fluvastatin equally inhibited IFN-gamma
      induced PBMNC CD40 expression from various genotypes (CC, CT, TT was 30.3%,
      26.3%, 29.3% respectively, all P > 0.05). CONCLUSION: Inflammatory cytokines were
      increased in ACS patients and CD40-1C/T polymorphism is associated with higher
      risk for ACS in Han Chinese.

PMID- 19099973
TI  - [Toll-like receptor 4 expression in the coronary atherosclerotic plaques of
      patients died from sudden cardiac death].
AB  - OBJECTIVE: To investigate the Toll like receptor 4 (TLR4) expression in the
      coronary atherosclerotic plaques in patients died from sudden cardiac death (SCD)
      or non SCD. METHODS: Autopsied coronary artery samples from 75 patients died from
      SCD (n = 28), non-SCD (n = 28) or non-CHD (n = 19) were examined and the R value
      (positive cells' areas/scanning areas) and A value (average optical density) of
      TLR4 expression in the coronary arteries were detected qualitatively by the
      immunohistochemistry (SABC method) and image analysis technologies. RESULTS: SCD
      group: 13 (46.4%) cases showed strong positive expression of TLR4; 11 (39.3%),
      positive expression; 4 (14.3%), weak positive expression. CHD group: 8 (28.6%)
      cases showed weak positive expression; 17 (60.7%), very weak positive expression;
      3 (10.7%), no positive expression. There was no positive expression of TLR4 in
      non-CHD samples. A (1.140 +/- 0.101) and R value (0.0269 +/- 0.0027) in SCD group
      were significantly higher than in non-SCD and control groups (all P < 0.01). A
      value was siginificantly higher in CHD group (0.719 +/- 0.205) than that in
      control group (0.481 +/- 0.033, P < 0.05) while R value (0.0085 +/- 0.0007,
      0.0046 +/- 0.0004) was similar between the groups (P > 0.05). CONCLUSION: The
      increased positive expressive of TLR4 in the atherosclerotic plaque can be
      regarded as an important pathological marker of SCD.

PMID- 19099974
TI  - [Peripheral dendritic cell subpopulation changes in patients with coronary artery
      disease].
AB  - OBJECTIVE: To compare the peripheral dendritic cell subpopulation changes in
      patients with or without coronary artery disease. METHODS: A total of 60 patients
      with angiographic documented coronary artery disease (CAD) were recruited in this
      study, including 20 cases with acute myocardial infarction (AMI group), 20 cases
      with unstable angina(UA group) and 20 patients with stable angina (SA group).
      Eleven patients with chest pain and without coronary stenosis served as chest
      pain control (CPS group). Ten cases without heart diseases served as normal
      control (Normal control group). Numbers of peripheral myeloid dendritic cell
      (mDC) and plasmacytoid dendritic cell (pDC) precursors were determined by FACS.
      RESULT: The proportions of mDC precursors were significantly lower in UA group
      and AMI group (4.7% +/- 2.6%, 5.0% +/- 2.7%) than that in SA, CPS and control
      groups (11.0% +/- 6.4%, 12.0% +/- 3.9%, 12.3% +/- 3.3%, respectively, all P <
      0.001). pDC numbers were similar among groups. CONCLUSION: Reduced circulating
      mDC subsets in patients with unstable angina and AMI might suggest enhanced mDC
      recruitment to vulnerable plaques in these patients.

PMID- 19099975
TI  - [Psychological stress status in patients with acute coronary syndrome and stable
      angina pectoris].
AB  - OBJECTIVE: To observe the psychological stress status in patients with acute
      coronary syndrome (ACS) and stable angina pectoris (SA). METHODS: The intensity
      of social psychological stress and the serum levels of IL-6, CRP and ICAM-1 were
      determined in patients with ACS (n = 67) and SA (n = 33). RESULTS: (1) The
      percentage of patients with psychological stress was significantly higher in ACS
      than that in SA group (78.8% vs. 21.2%, P < 0.01). (2) The serum levels of CRP
      [(14.82 +/- 5.07) g/L vs. (8.78 +/- 4.34) g/L], IL-6 [(101.7 +/- 22.2) ng/L vs.
      (71.1 +/- 23.5) ng/L] and sICAM-1 [(1.41 +/- 0.47) mg/L vs. (0.82 +/- 0.37) mg/L]
      were significantly higher in psychological stress group than those in non
      psychological stress group (all P < 0.05). Serum CRP [(18.91 +/- 3.12) g/L vs.
      (6.20 +/- 2.46) g/L], IL-6 [(114.6 +/- 15.2) ng/L vs. (56.4 +/- 15.8) ng/L] and
      sICAM-1 [(1.67 +/- 0.39) mg/L vs. (0.63 +/- 0.28) mg/L] levels in ACS group were
      significantly higher than those in SA group (all P < 0.01). CONCLUSION: Higher
      psychological stress was associated with higher risk of ACS and increased serum
      inflammatory cytokines.

PMID- 19099976
TI  - [Detection of periodontal pathogenic bacteria DNA in coronary atheromatous
      plaques from patients underwent coronary artery bypass graft].
AB  - OBJECTIVE: The aim of this study was to observe the coexistence of periodontal
      bacteria DNA (Actinobacillus actinomycetemcomitans, Fusobacterium nucleatum,
      Porphyromonas gingivalis, Prevotella intermedia, Tannerella. forsythensis) in
      coronary atheromatous plaques and subgingival plaques in patients scheduled for
      coronary artery bypass graft. METHODS: Coronary atheromatous plaque and
      subgingival plaque samples were obtained from 51 patients and examined by
      polymerase chain reaction (PCR) technique with specific primers for periodontal
      bacteria. RESULTS: P. gingivalis (33%), T. forsythensis (31%), P. intermedia
      (18%) and F. nucleatum (12%) were detected while A. actinomycetemcomitans was
      negative and not found in coronary atheromatous plaques; T. forsythensis (84%),
      F. nucleatum (78%), P. intermedia (59%), P. gingivalis (39%) and A.
      actinomycetemcomitans (22%) were detected in subgingival plaque samples.
      Coexistence of periodontal bacteria DNA in coronary atheromatous and subgingival
      plaque samples was evidenced in 32 patients. CONCLUSIONS: The coexistence of T.
      forsythensis, F. nucleatum, P. intermedia, P. gingivalis in coronary atheromatous
      plaques and the subgingival plaque samples in CAD patients could suggest a
      potential role for periodontal pathogenic bacteria in atherosclerosis disease
      process.

PMID- 19099977
TI  - [Circulating cytokine measurements by protein chips in patients with acute
      coronary syndrome].
AB  - OBJECTIVE: To observe the feasibility of measuring multiple circulating cytokines
      by protein chips in patients with acute coronary syndrome (ACS). METHODS:
      Circulating cytokines were determined by protein chips in 50 control cases and
      104 ACS cases of unstable angina pectoris (UA, n = 50) and acute myocardial
      infarction (AMI, n = 54) cases. RESULTS: The levels of serum MMP-9, sCD40L, CRP,
      IL-6, H-FABP, cTnI and plasma IL-8, NT-proBNP, sVCAM-1, ET-1 in ACS group were
      significantly higher than those in the control group (all P < 0.01). Serum H-FABP
      and cTnI were significantly higher in AMI patients than in UA patients (P <
      0.01). Serum MMP-9, sCD40L, CRP, IL-6 and plasma sVCAM-1, ET-1 tended to be
      higher in AMI patients as compared to UA patients (all P > 0.05). Serum MMP-9,
      sCD40L, and H-FABP were positively correlated with the severity of angina(r =
      0.653, r = 0.745, r = 0.933, P < 0.01, respectively). Serum MMP-9, sCD40L, and H
      FABP increased in proportion to the levels of Braunwald angina classes in UA
      patients (angina class I < angina class II < angina class III, P < 0.01).
      CONCLUSIONS: Circulating cytokines were significantly increased in ACS patients
      and positively correlated to Braunwald angina classes in UA patients.

PMID- 19099978
TI  - [Diagnostic value of 128-slice CT coronary angiography in comparison with
      invasive coronary angiography].
AB  - OBJECTIVE: To observe the diagnostic value of non-invasive 128-slice computed
      tomography coronary angiography (CTA) in comparison with invasive coronary
      angiography. METHODS: 128-slice CTA and invasive coronary angiography were
      performed in 78 unselected consecutive patients (63 patients with suspected
      coronary artery disease and 15 patients with previous coronary stenting, 56
      males, mean age 61 +/- 10 years) and > 50% reduction of minimal lumen diameter
      was defined as significant coronary stenosis. RESULTS: Fifty-eight out of 879
      segments (7%) from CTA were not assessable because of irregular rhythm, vessel
      calcification or tachycardia. Compared with invasive coronary angiography,
      segment-based analysis from the 821 segments showed the sensitivity by CTA was
      87%, specificity 97%, PPV 83% and NPV 97%. Four out of 22 stents implanted in 15
      patients were not assessable by CTA because of poor image quality. Compared with
      invasive coronary angiography, the sensitivity of diagnosing in-stent restenosis
      by CTA was 100%, specificity 77%, PPV 63% and NPV 100% for the remaining 18
      stents. CONCLUSIONS: One hundred and twenty-eight-slice CTA has a high accuracy
      for detecting coronary artery disease and in-stent restenosis after coronary
      stenting and could be considered as a valuable noninvasive technique for
      screening coronary artery disease in suspected patients.

PMID- 19099979
TI  - [Association between higher blood pressure level in children and adult blood
      pressure: 17 years follow-up results].
AB  - OBJECTIVE: Essential hypertension may begin at childhood. The aim of this study
      is to identify the risk factors of hypertension and detect the evolvement
      tracking of blood pressure in childhood. METHODS: In this study, we followed up
      blood pressure changes in 4623 school children (6 - 15 years-old) from 1987 to
      2005 in Hanzhong rural area. A total of 152 children were grouped to higher blood
      pressure group [systolic blood pressure (P(SBP)) >or= 75(th) (P(75))] and 140
      children grouped to normal blood pressure group [P(SBP) < 50(th) (P(50))] and
      their blood pressure were re-measure 18-years later. RESULTS: The total follow-up
      rate was 70.2%. Follow-up blood pressure was significantly higher in higher blood
      pressure group at baseline than that in normal blood pressure group at baseline
      (P < 0.05). The hypertension rate at follow up was significantly higher in higher
      blood pressure group at baseline than that in normal blood pressure group at
      baseline (28.0% vs. 4.1%, P < 0.01). The risk for hypertension was 6.88 greater
      in higher blood pressure group at baseline than that in normal blood pressure
      group at baseline. CONCLUSIONS: Higher blood pressure at childhood is a risk of
      developing hypertension at adulthood.

PMID- 19099980
TI  - [Serum adiponectin and free fatty acid profile in essential hypertensive patients
      with or without metabolic syndrome].
AB  - OBJECTIVE: To observe serum adiponectin, free fatty acid (FFA) profile and other
      glucose and lipid metabolic parameters in essential hypertensive patients with
      metabolic syndrome (HPMS) or without metabolic syndrome (HP). METHODS: The serum
      adiponectin was measured with the radioimmunoassay, FFA profile measured with the
      gas chromatography and mass spectrometer in 72 HPMS, 56 HP and 43 normal control
      subjects. RESULTS: Serum adiponectin were significantly lower in HPMS group than
      those in the HP and control group (P < 0.05 or P < 0.01). Serum total free fatty
      acid (TFA), unsaturated fatty acid (UFA, linoleic acid, oleic acid, arachidonic
      acid, docosahexaenoic acid, eicosatrienoic acid), polyunsaturated fatty acid
      (PUFA) and n6PUFA were significantly higher in HPMS group than those in the HP
      and control groups (P < 0.05 or P < 0.01). Adiponectin was negatively correlated
      with body mass index, waist circumferences, waist hip ratio, triglycerides (r = 
      0.222, -0.235, -0.179, -0.194, P < 0.01 or P < 0.05, respectively) and positively
      correlated with high-density lipoprotein cholesterol (r = 0.336, P < 0.01); TFA
      and PUFA were positively correlated with body mass index, waist circumferences,
      fasting blood glucose, mean arterial pressure (r = 0.241 and 0.280, 0.198 and
      0.188, 0.226 and 0.298, 0.274 and 0.334, P < 0.01 or P < 0.05, respectively) in
      all subjects. CONCLUSION: Our data suggest that changes in serum adiponectin, FFA
      and n6PUFA might promote the development of metabolic syndrome in essential
      hypertensive patients.

PMID- 19099981
TI  - [Study on six-minute walk test and cardiac output response against exercise in
      patients with chronic heart failure].
AB  - OBJECTIVE: To evaluate the significance of cardiac output (CO) response against
      exercise determined by IGR method and LVEF, 6 MWT distance in patients with
      chronic heart failure (CHF). METHOD: To adopt 6 MWT, and before and after the
      test measuring the CO by the IGR method, furthermore, measure LVEF to 36 patients
      (heart failure group) with CHF, compare with the health groups (control group).
      RESULTS: The 6MWT distance of heart failure group (333.00 +/- 49.64) m decrease
      compared with the control group (582.56 +/- 67.97) m (P < 0.01), moreover, the
      distance of NYHA class III (314.82 +/- 36.27) m is significantly shorter than II
      (361.57 +/- 55.42) m (P < 0.05). The LVEF of heart failure group (47.0 +/- 0.4)%
      reduce compared with the control group (66.9 +/- 5.2)% (P < 0.01), and the data
      of NYHA class III (43.3 +/- 10.3)% is significantly lower than II (52.8 +/- 7.6)%
      (P < 0.01). The increase in CO response against exercise of heart failure group
      (5.97 +/- 1.89) L/min decrease compared with control group (8.88 +/- 0.52) L/min
      (P < 0.01), furthermore, the value of NYHA class III (5.31 +/- 1.52) L/min,
      compared with II (7.01 +/- 1.98)L/min, is obviously lower (P < 0.01). The 6MWT
      distance correlates positively with the increase in CO response against exercise
      (r = 0.63, P < 0.01), but the correlation is not found between the increase CO
      response against exercise and the LVEF (r = 0.11, P > 0.05). CONCLUSION: Our
      results show that CO response against exercise measured by IGR method, with the
      advantages of being noninvasive, safe, convenient and accurate, combining with
      the 6MWT can evaluate cardiac reserve in patient with CHF.

PMID- 19099982
TI  - [Identification of human coronary artery endothelial cells obtained by coronary
      endovascular biopsy].
AB  - OBJECTIVE: To develop a method to obtain and identify human coronary artery
      endothelial cells obtained during percutaneous coronary interventions (PCI).
      METHODS: Coronary guide wires were used to obtain endothelial cells from coronary
      arteries in 28 patients undergoing PCI. The cells were eluted from the wire tips
      and then purified by magnetic beads coated with anti-CD146 antibody. von
      Willebrand factor (vWF) was used as an immunocytochemical marker for endothelial
      cells. The cellular viability was evaluated by observing cell membrane integrity
      and energy-dependent uptake of DiI-labeled acetylated low-density lipoprotein.
      RESULTS: An average of 96 coronary artery endothelial cells with good viability
      per patient were obtained by one guide wire. vWF identification showed their
      endothelial morphology and immunoreactivity. CONCLUSION: The viable coronary
      endothelial cells could be obtained during routine percutaneous coronary
      interventions combined with magnetic beads isolation technique. These cells may
      be used for further cellular functional analyses (such as immunocytochemistry and
      molecular biology) and expand our understanding on mechanisms of coronary artery
      diseases.

PMID- 19099983
TI  - [In vivo interleukin-10 gene transfer down-regulates myocardial matrix
      metalloproteinase and myocardial collagen expressions in rats with acute
      myocardial infarction].
AB  - OBJECTIVE: We investigated the in vivo effects of recombinant adenovirus
      associated virus type-2 (AAV-2) mediated interleukin-10 (IL-10) gene transfer on
      the expression of matrix metalloproteinase (MMP)-2, 9, tissue inhibitor of
      metalloproteinase (TIMP)-1, collagen type I and type III in a rat acute
      myocardial infarction model. METHOD: Male Sprague-Dawley (SD) rats were randomly
      divided into three groups (each n = 6): sham operation group, MI/AAV2 group, and
      MI/AAV2-IL-10 group (10(10) vg/ml x 0.1 ml injection at peri-infarct regions
      immediately post MI). Five days later, the expressions of MMP-2 and MMP-9 were
      measured by RT-PCR, Western blot and zymography. The expression of TIMP-1 was
      measured by RT-PCR and Western blot. Collagen type I and type III were assessed
      by RT-PCR and immunohistochemical stain. RESULTS: The myocardial expressions of
      MMP-2, MMP-9 and collagen contents in MI/AAV2 group were significantly increased
      than those in sham operation group. Myocardial expressions of MMP-2, MMP-9 were
      significantly decreased and the expression of TIMP-1 significantly increased in
      the MI/AAV2-IL-10 group than those in MI/AAV2 group. Moreover, the expressions of
      collagen type I, collagen type III and the ratio of I/III collagen in border
      zones of infarcted myocardium were decreased by 47.6% (P < 0.01), 23.6% (P <
      0.05), and 17.9% (P < 0.05) respectively, while the expression of TIMP-1
      increased by 73.1%(P < 0.05) in MI/AAV2-IL-10 group compared to MI/AAV2 group.
      CONCLUSION: In vivo myocardial IL-10 transfer reduced myocardial MMP and collagen
      expression and increasing the TIMP expression.

PMID- 19099984
TI  - [Effects of RNA interference targeting angiotensin-converting enzyme on the blood
      pressure and myocardial remodeling in spontaneously hypertensive rats].
AB  - OBJECTIVE: To investigate the effects of RNA interference (RNAi) targeting
      angiotensin-converting enzyme (ACE) on the blood pressure and myocardial
      remodeling in spontaneously hypertensive rats (SHRs). METHODS: Saline (control),
      adenovirus (Ad5) and recombinant adenoviral vectors (Ad5-ACE-shRNA expressing ACE
      gene-specific shRN) were randomly administered by caudal intravasation to SHRs (n
      = 12 each group) at day 1 and day 16. Normotensive Wistar-Kyoto rats (WKY) served
      as normal controls. Systolic blood pressure (SBP) of the caudal artery was
      measured daily. Expressions of ACE at mRNA and protein levels in myocardium and
      aorta were evaluated by RT-PCR and Western blot respectively, ACE serum
      concentration was measured by ELISA at day 3 (n = 6 each group). The ratio of
      left ventricular to body weight (LVW/BW), myocardial collagen content were
      measured and myocardial ultrastructure observed under transmission electron
      microscope at the study end. RESULTS: Ad5-ACE-shRNA injection significantly
      reduced SBP (-22 mm Hg, 1 mm Hg = 0.133 kPa) and the antihypertensive effect
      could last at least 14 days post each injection. SBP was not affected by saline
      and Ad5 injections. ACE expressions at mRNA and protein levels at myocardium and
      aorta as well as serum ACE were significantly decreased in Ad5-ACE-shRNA treated
      SHRs compared to that in saline and Ad5 groups (all P < 0.05) and was comparable
      to that in WKY group (P > 0.05). The LVW/BW ratio (2.24 +/- 0.19) and myocardial
      collagen content [(1.283 +/- 0.019) microg/mg] in Ad5-ACE-shRNA treated SHRs were
      also significantly lower than those in saline treated [3.21 +/- 0.13 and (1.686
      +/- 0.013) microg/mg, both P < 0.05] and Ad5 treated SHRs [3.13 +/- 0.12, (1.682
      +/- 0.009) microg/mg, both P < 0.05] but still higher than those of WKY group
      [2.06 +/- 0.11, (1.257 +/- 0.019) microg/mg, both P < 0.05]. Myocardial
      ultrastructure was also significantly improved in Ad5-ACE-shRNA treated SHRs
      compared to saline and Ad5 treated SHRs. CONCLUSION: RNAi targeting ACE gene
      significantly inhibited the expressions of ACE at mRNA and protein levels and
      resulted in prolonged antihypertensive effects and myocardial ultrastructure
      improvements in this SHR model.

PMID- 19099985
TI  - [Granulocyte colony stimulating factor attenuated myocardial apoptosis via Janus
      kinase 2/signal transducer and activator of transcription signal transduction
      pathway in rats with coronary microembolization].
AB  - OBJECTIVE: To investigate the effects of granulocyte colony stimulating factor (G
      CSF) on myocardial apoptosis following coronary microembolization (CME) and
      possible role of Janus kinase/singnal transducer and activator of transcription
      (JAK/STAT) pathway in this process. METHODS: A total of 92 male Sprague Dawley
      rats were randomized into CME (n = 24), G-CSF (100 microg x kg(-1) x d(-1) i.p. 2
      hours post CME for 5 days, n = 24), JAK2 inhibitor AG490 (G-CSF plus AG490, 5 mg
      x kg(-1) x d(-1) i.p. 2 hours post CME for 5 days, n = 24), all rats received
      left ventricular injection of homologous microthrombotic particle suspension post
      clamping the ascending aorta. Sham-operated group (n = 20) served as control. The
      rats were sacrificed at day 3, 7, 14 and 28 after operation. The myocardial mRNA
      expressions of Bcl-2, Bax, Fas, FasL and GAPDH which was used as the
      intercomparison, were evaluated by real time PCR. The ratio of Bcl-2/Bax was
      compared. The protein expression of Caspase-3, cleaved PARP, t-JAK2, p-JAK2, t
      STAT3 and p-STAT3 were detected by western blot. Myocardial apoptosis were
      examined by TUNEL staining. RESULTS: Compared with Sham rats, the mRNA of Bcl-2,
      Bax, Fas and FasL significantly increased whereas the ratio of Bcl-2/Bax (0.28 +/
      0.04 vs. 2.98 +/- 0.49) significantly decreased and the protein expression of
      Caspase-3 (0.762 +/- 0.129 vs. 0.133 +/- 0.027), PARP (0.992 +/- 0.146 vs. 0.386
      +/- 0.074) and the myocardial apoptosis index (17.2 +/- 1.9 vs. 1.2 +/- 0.6)
      significantly increased in CME hearts (all P < 0.05). rhG-CSF significantly
      attenuated CME induced changes and cotreatment with JAK2 inhibitor AG490
      abolished the effects of rhG-CSF. The protein expressions of t-JAK2 and t-STAT3
      among the groups were similar. P-JAK2 and p-STAT3 protein expressions were
      significantly increased in G-CSF group compared to other groups (P < 0.05).
      CONCLUSION: G-CSF attenuated myocardial apoptosis induced by CME via JAK2/STAT3
      pathway.

PMID- 19099986
TI  - [Overexpression of sarcoplasmic reticulum calcium ATPase induced hemodynamic and
      proteomic changes in a dog model of heart failure].
AB  - OBJECTIVE: Overexpression of SERCA2a could improve cardiac function in human and
      experimental heart failure (HF) models. We observed the proteomics changes post
      SERCA2a overexpression in a pacing induced HF model in dogs. METHODS: Beagles
      were divided into four groups: control group, HF group (230 beats/min for 4
      weeks), HF + EGFP group (myocardial injection of 1 x 10(12) v.g recombinant adeno
      associated virus carrying enhanced green fluorescent protein gene, rAAV2/1-EGFP)
      and HF + SERCA2a group (myocardial injection of 1 x 10(12) v.g recombinant adeno
      associated virus carrying SERCA2a gene, rAAV2/1-SERCA2a). Thirty days after gene
      transduction, left ventricular systolic and diastolic functions were measured by
      echocardiography and invasive hemodynamics in all animals. By use of 2
      dimensional gel electrophoresis (2-DE), -500 distinct protein spots were detected
      in myocardium of all animals. Protein spots observed to be altered between
      failing and SERCA2a overexpressed hearts were subjected to tryptic peptide mass
      fingerprinting for identification by MALDI-TOF mass spectrometry in combination
      with LC/MS/MS analysis. RESULTS: At 30 day after gene transfer, HF signs were
      significantly reduced, cardiac function [LVSP: (214.72 +/- 31.74) mm Hg (1 mm Hg
      = 0.133 kPa) vs. (139.32 +/- 36.79) mm Hg, +dp/dt(max): (6779.43 +/- 217.58) mm
      Hg/s vs. (2746.85 +/- 931.23) mm Hg/s and -dp/dt(max): (-4341.42 +/- 322.02) mm
      Hg/s vs. (-2531.14 +/- 616.15) mm Hg/s, LVEDP: (21.86 +/- 6.95) mm Hg vs. (59.78
      +/- 6.92) mm Hg] significantly improved in HF + SERCA2a dogs than those in HF +
      EGFP group(all P < 0.05) and parameters were comparable between HF + SERCA2a and
      control groups. We identified alterations in the expression level of more than 10
      proteins in myocardium. These protein changes were observed mainly in two
      subcellular compartments: the cardiac contractile apparatus and
      metabolism/energetics. CONCLUSION: These results showed that overexpression of
      SERCA2a could improve cardiac function accompanied with numerous alterations in
      protein expressions involved in calcium handling, myofibrils, and energy
      production in this dog model of chronic heart failure.

PMID- 19099987
TI  - [Recombinant human growth hormone promotes in vitro mesenchymal stem cell
      growth].
AB  - OBJECTIVE: To detect the effect of recombinant human growth hormone (rhGH) to
      mesenchymal stem cells (MSCs) in vitro. METHODS: Various concentrations of rhGH
      (terminal concentrations 1, 10, 50, 100, 200 and 500 microg/L) were added to
      medium containing the second generation of MSCs, A value was measured by MTT
      method at various concentrations and at 24, 48 and 72 h. The expression of
      insulin-like growth factor 1(IGF-1) mRNA in the presence (24, 48 and 72 h) or
      absence (the 4(th) day, the 9(th) day, the 10(th) day, the 2(nd) week, the 3(rd)
      week and the 4(th) week post removal of rhGH) of various rhGH concentrations was
      determined by RT-PCR. RESULTS: rhGH could promote the MSCs growth at
      concentration > 10 microg/L in a time-dependent manner. The optimal concentration
      was 200 microg/L with a growth rate 144.74%. The expression of IGF-1 mRNA
      increased in a time-dependent manner gradually (0.6749 +/- 0.0084, 0.7781 +/-
      0.0068, 0.8230 +/- 0.0060 at 24, 48 and 72 h, respectively at 200 microg/L rhGH).
      After rhGH withdraw, the expression of IGF-1 mRNA decreased in a time-dependent
      manner till 2 weeks (0.5287 +/- 0.0077, 0.5747 +/- 0.0050, 0.6068 +/- 0.0056,
      0.7071 +/- 0.0089, 0.5791 +/- 0.0057, 0.5781 +/- 0.0081 at the 4(th) day, the
      9(th) day, the 10(th) day, the 2(nd) week, the 3(rd) week and the 4(th) week post
      removal of rhGH). CONCLUSION: rhGH could promote the growth of MSCs in vitro.

PMID- 19099990
TI  - [Transcatheter closure of twist coronary fistula between left coronary artery and
      left ventricular].

PMID- 19099991
TI  - [Transient lower limbs dysfunction in a patient after aortic dissecting
      aneurysm].

PMID- 19099992
TI  - [Coronary sinus drainage into left atrium: 2 cases report].

PMID- 19099993
TI  - [Surgical retrieval for a late dislocated atrial septal occluder device].

PMID- 19099994
TI  - [CT diagnosis of a huge congenital left ventricular diverticulum in an adult: a
      case report].

PMID- 19099995
TI  - [Functional evaluation of coronary microcirculation].

PMID- 19099996
TI  - [A case report of an early pregnancy complicated with acute myocardial
      infarction].

PMID- 19099997
TI  - [Evaluation of nonatherosclerotic coronary artery stenosis].

PMID- 19100000
TI  - [Dysplastic cardiomyopathy and its relationship with cardiac development].

PMID- 19100001
TI  - [Clinical and angiographic predicting factors leading to unfavorable myocardial
      reperfusion in patients with acute ST-elevation myocardial infarction after
      primary percutaneous coronary intervention].
AB  - OBJECTIVE: To investigate the clinical and angiographic morphologic features
      leading to worse myocardial reperfusion in patients with acute ST-elevation
      myocardial infarction (STEMI) after primary percutaneous coronary intervention
      (PCI). METHODS: Clinical and angiographic data were collected and logistic
      regression analysis performed in 964 STEMI patients undergoing primary PCI.
      RESULTS: Logistic regression analysis showed that non-anterior myocardial
      infarction, pain to balloon time and degree of cardiac dysfunction were clinical
      predictive factors while fade-out type of angiographic morphology, ie, presence
      of accumulated thrombus proximal to the occlusion was angiographic predictive
      factor of worse reperfusion for STEMI patients post PCI. CONCLUSION: These
      predictive clinical and angiographic morphologic factors in STEMI patients for
      worse myocardial reperfusion post PCI could help to identify patients at high
      risk post PCI.

PMID- 19100002
TI  - [Management and outcome of 47 patients with acute myocardial infarction
      complicating cardiogenic shock].
AB  - OBJECTIVE: To evaluate the clinical outcomes of patients with acute myocardial
      infarction (AMI) complicating cardiogenic shock underwent various treatments.
      METHODS: From January, 2002 to May, 2007, 47 AMI patients with cardiogenic shock
      were treated in our department by optimal medication (dopamine, epinephrine,
      norepinephrine, etc.), intra-aortic balloon pump (IABP), mechanical ventilation
      when indicated, percutaneous coronary intervention (PCI) or coronary artery
      bypass graft (CABG). Outcome and factors related to mortality for these patients
      were analyzed in this retrospective study. RESULTS: Besides optimal medication
      and IABP in all patients, 31 patients underwent PCI (66.0%), 6 patients received
      emergency CABG (12.8%). The overall in-hospital mortality rate was 36.2% (17/47),
      6 patients (14.9%) died before coronary revascularization and 11 patients (21.3%)
      died after revascularization. Nine patients died of pump failure and 8 patients
      died of renal and (or) respiratory failure. Regression analysis showed that acute
      renal failure (r = 0.734, P = 0.000), acute respiratory failure (r = 0.606, P =
      0.000) and diabetes (r = 0.372, P = 0.012) were positively related to in-hospital
      mortality. CONCLUSION: Despite improvements in treatment options for AMI patients
      complicating cardiogenic shock, in-hospital mortality remained high, especially
      for patients complicating further with acute renal failure and acute respiratory
      failure.

PMID- 19100003
TI  - [A randomized, double-blind, double-dummy study comparing a fixed dose
      combination of telmisartan 80 mg plus hydrochlorothiazide 12.5 mg to telmisartan
      80 mg in Chinese hypertensive patients who failed to respond adequately to
      telmisartan 80 mg].
AB  - OBJECTIVE: To evaluate the efficacy and safety of a fixed dose combination of
      telmisartan 80 mg plus hydrochlorothiazide (HCTZ) 12.5 mg (TH) to telmisartan 80
      mg (T) in Chinese patients who failed to respond adequately to treatment with T.
      METHOD: This is a multi-center, randomized, double-blind, double-dummy clinical
      study. A total of 699 eligible hypertensive patients entered a one-week screening
      phase prior to the eight-week open-label T period. At the end of eight weeks, 345
      patients who failed to respond to T (DBP > or = 90 mm Hg, 1 mm Hg = 0.133 kPa)
      were randomized to receive either TH (175 patients) or T (170 patients) for
      another eight weeks. Sitting and standing BP were taken 24 hours post-dose and
      adverse events were documented at visit with 4 weeks interval. Laboratory, ECG
      and physical examination were performed at screening, at baseline and at the
      final visit. RESULTS: After 8 weeks treatment, (1) The mean trough reduction in
      sitting diastolic blood pressure (SiDBP) from baseline in TH group was greater
      than that in T group (10.1 mm Hg vs 7.7 mm Hg, P = 0.0017). The mean trough
      reduction in sitting systolic blood pressure (SiSBP) from baseline was 14.2 mm Hg
      in TH group and 7.4 mm Hg in T group (P < 0.0001). (2) The mean trough reduction
      in standing DBP and standing SBP from baseline were significantly greater in TH
      group (8.7 mm Hg and 12.9 mm Hg) compared those in T group (7.3 mm Hg and 7.0
      mmHg, P = 0.0350, P < 0.0001). (3) The number and percentage of responders in TH
      group (129, 74.6%) were significantly higher than in T group (100, 59.2%, P =
      0.0016). (4) The incidence of the study drug-related adverse events was similar
      between TH and T group (3.5% vs. 3.6%, P > 0.05). CONCLUSION: TH was more
      effective than T in patients not responded adequately to T in Chinese
      hypertensive patients.

PMID- 19100004
TI  - [Relationship between Ghrelin polymorphism and serum lipoprotein levels in Han
      Chinese with or without coronary heart disease risk factors].
AB  - OBJECTIVE: To investigate the relationship between polymorphism of Ghrelin gene
      and serum levels of lipoprotein in Han Chinese with or without coronary heart
      disease (CHD) risk factors. METHODS: PCR restriction fragment length polymorphism
      assay was used to detect the distribution of genotypes of Ghrelin gene in 225 Han
      Chinese (40 to 69 years-old) with CHD risk factors, 78 subjects without CHD risk
      factors served as normal controls. Serum levels of total cholesterol (TC),
      triglyceride (TG), high density lipoprotein-cholesterol (HDL-C), low density
      lipoprotein-cholesterol (LDL-C) and very low-density lipoprotein (VLDL) were
      measured to analyze the relationship with the polymorphism of Ghrelin gene.
      RESULTS: Ghrelin genotype frequencies of AA, AG, GG (0.975, 0.025, 0.00 in
      control group and 0.956, 0.040, 0.004 in the high-risk group, all P > 0.05) as
      well as the allele frequencies of A, G (0.987, 0.013 in control group and 0.976,
      0.024 in the high-risk group, all P > 0.05) were similar between the groups. HDL
      C levels of the Arg/Gln carriers were significantly lower than those of Arg/Arg
      carriers in control group and in the high-risk group (all P < 0.05). CONCLUSION:
      Arg/Gln carriers were associated lower HDL-C levels in Han Chinese.

PMID- 19100005
TI  - [The prospective study on the prognosis in patients with ventricular tachycardia
      or fibrillation treated with implantable automatic cardioverter defibrillator].
AB  - OBJECTIVE: To explore the effect of implantable automatic cardioverter
      defibrillator (ICD) on improvement of the prognosis of patients with ventricular
      tachycardia or fibrillation (VT/VF). To compare the advantages and disadvantages
      of ICD with antiarrhythmic drug, to select the best indication of ICD and review
      the protocol of the following-up of ICD patients, and present scientific evidence
      for the morebroad popularization who needs ICD in China. METHODS: In 99 selected
      patients who had the indication of class I, 27 patients were treated by ICD (ICD
      group), and 72 patients were not (non-ICD group). Patients in the two groups had
      the similar basic clinical characteristics. The incidence of syncope, CPR, and VF
      in ICD group were more common than those in non-ICD group. Patients in the two
      groups received same basic therapy. The total mortality rate and the incidence of
      cardiac events in two groups were compared in 3 months, 6 months, 12 months and
      15 months. RESULTS: The total mortality rate and the incidence of cardiac events
      in ICD group were significantly lower than those in non-ICD group in the follow
      up period. The mortality rate in ICD group is 0, and the mortality rate in non
      ICD group is 20.8%. CONCLUSIONS: (1) ICD treatment can decrease the incidence of
      cardiac events of patients with high risk of sudden cardiac death (SCD), and
      improve their survival. (2) The key measures to insure the efficacy, safety, and
      cost-effectiveness of ICD treatment is: to select the patients correctly, to
      optimize the implanting process and the follow-up, and use rational assistant
      therapy.

PMID- 19100006
TI  - [The Val606Met mutation of human beta myosin heavy chain in a Chinese familial
      hypertrophic cardiomyopathy family].
AB  - OBJECTIVE: To explore the disease-causing gene mutation in Chinese families with
      hypertrophic cardiomyopathy (HCM) and to analyze the correlation between the
      genotype and phenotype. METHODS: Samples of peripheral blood were collected from
      three Chinese families with HCM (at least two HCM patients existed/family). The
      exons in the functional regions of the beta myosin heavy chain gene (MYH7) were
      amplified with PCR and the products were sequenced. RESULTS: A Val606Met missen
      mutation was identified in the exon 16 of MYH7 gene in a Chinese family and this
      mutation was identified in all HCM patients (n = 4) and there was also a 15-years
      old young mutation carrier who was not HCM patient now (penetrance of 80%). This
      mutation was not identified in other healthy family members in this family, in
      other 2 Chinese familiar HCM families and in 120 non-HCM control patients.
      CONCLUSION: The Val606Met missen mutation is closely associated with familiar HCM
      in a Chinese family which is associated with clinical phenotype with a penetrance
      of 80%.

PMID- 19100007
TI  - [Myocardial involvement in 2494 patients with systemic lupus erythematosus].
AB  - OBJECTIVE: To investigate the clinical characteristics and related pathogenetic
      factors in systemic lupus erythematosus (SLE) patients with myocardial
      involvement. METHODS: Clinic data and myocardial involvements were analyzed in
      2494 SLE patients who admitted to our hospital from 1997 to 2007. RESULTS:
      Myocardial involvements were seen in 13 out of 2494 SLE patients (0.52%). Dyspnea
      of various degrees and left ventricular systolic dysfunction are frequently found
      in these patients with myocardial involvements. Glucocorticoid therapy
      significantly increased left ventricular ejection fraction (LVEF, 37.7% +/- 5.8%
      vs. 40.9% +/- 7.1%, P = 0.002). Significant associations were found between anti
      rRNP antibody and LVEF (r = 0.843, P = 0.001) as well as between cardiac troponin
      I (cTnI) and left ventricular end diastolic diameter (LVEDD) (r = 0.656, P =
      0.036). CONCLUSIONS: Myocardium is rarely affected in patients with SLE in this
      cohort. Echocardiography is a valuable method for detecting cardiac abnormalities
      in patients with SLE. Glucocorticoid therapy could improve cardiac function in
      SLE patients with cardiac involvement and serological factors are related to
      cardiac functions.

PMID- 19100008
TI  - [Role of transoesophageal echocardiography on periventricular closure of
      ventricular septal defects].
AB  - OBJECTIVE: To evaluate the clinical value of transoesophageal echocardiography on
      periventricular closure of ventricular septal defects (VSD). METHODS:
      Transoesophageal echocardiography (TEE) was performed in 27 patients with VSD
      diagnosed by the transthoracic echocardiography examination (TTE) and prepared to
      receive periventricular closure of VSD for the purposes of choosing the
      appropriate occluder before VSD closure and guiding occluder release during the
      operation and evaluating the post operative effects of VSD closure 1 week post
      operation. RESULTS: Three patients with VSD not suitable for periventricular VSD
      closure according to TEE results were not operated, periventricular closure of
      VSD were successfully performed in 20 patients and minimal residual shunt was
      seen in 1 patient post operation, periventricular closure of VSD failed in 4
      patients and these patients received surgical closure. TEE at 1 week post
      successfully with periventricular closure of VSD in the 20 patients showed that
      there were no residual shunts and the pulmonary artery pressure was significantly
      lower post operation compared to that of preoperation value. CONCLUSION: TEE is
      helpful in choosing the suitable patients and occlude size, guiding occlude
      release and evaluating the post operative results for periventricular closure of
      ventricular septal defects.

PMID- 19100009
TI  - [Clinical characteristics in adults and children with vasovagal syncope].
AB  - OBJECTIVE: To analyze the clinical characteristics in adults and children with
      vasovagal syncope (VVS). METHODS: Clinical data including head-up tilt table
      (HUTT) results were analyzed and compared in 136 children (mean age 12.3 +/- 2.7
      years, 50 boys, 86 girls) and 119 adults (mean age 36.4 +/- 14.0 years, 29 men,
      90 women) with VVS. RESULTS: (1) There were more female VVS patients in adults
      group than that in children group (male and female ratio: children group 1:1.7
      and adults group 1:3.1, P = 0.033) in this cohort. (2) The incidence of chest
      distress in adults group was significantly higher than that in children group
      [45.4 (54/119) vs. 27.2% (37/136), P = 0.003] while the incidence of headache
      [10.9% (13/119) vs. 20.6% (28/136), P = 0.036] and abdominal pain in children
      group was significantly higher than that in adults group [7.6% (9/119) vs. 19.1%
      (26/136), P = 0.008]. (3) Incidences of muggy environment [22.8% (26/114) vs.
      12.5% (17/136), P = 0.032] and urination VVS [9.7% (11/114) vs. 1.5% (2/136), P =
      0.004] were significantly higher in adults group than those in children group.
      (4) The mean time of mixed response vasogal episode in adults group was
      significantly longer than that in children group in sublingual nitroglycerin head
      up tilt table test (SNHUT) stage (5.04 +/- 2.27 min vs. 3.50 +/- 1.24 min, P =
      0.036). CONCLUSIONS: The incidences of chest distress, muggy environment and
      urination VVS were more often and the mean time of vasogal episode of mixed
      response in SNHUT stage was longer in adults VVS while the incidence of abdominal
      pain and headache was higher in children VVS patients compared to adults VVS
      patients.

PMID- 19100010
TI  - [Cardiac manifestations in Sjogren syndrome].
AB  - OBJECTIVE: To analyze the cardiac manifestations of patients with primary and
      secondary Sjogren syndrome. METHODS: Clinical data (clinical manifestations,
      serologic measurements, echocardiogram) of 396 patients with Sjogren syndrome who
      admitted to our hospital from 2004--2007 were retrospectively analyzed. Patients
      with congenital, rheumatic and coronary heart diseases, hypertension and diabetes
      (n = 221) and patients with incomplete clinic data (n = 51) were excluded.
      RESULTS: A total of 124 cases were included in this analysis (mean age 47.4 years
      old; 5 males; average disease duration 85.5 months). Cardiac involvement in
      Sjogren syndrome is usually asymptomatic. Pericardial effusion (PE) were
      evidenced in 20.2%, left ventricular diastolic dysfunction (LVDD) in 13.7%,
      pulmonary artery hypertension (PAH) in 12.9%, left atrium enlargement/in 7.3%,
      mitral insufficiency in 4.8%, aortic dilation in 5.6%, tricuspid insufficiency in
      3.2%, left ventricular enlargement in 2.4% and left ventricular systolic
      dysfunction in 0.8% patients by echocardiography examinations. Patients with PE
      had significantly lower CH50, C3, C4 levels and significantly higher C reactive
      protein level (CRP) and SSA positive rate than patients without PE (all P <
      0.05). The serum level of CRP was significantly associated with PE (OR 0.976, 95%
      CI 0.956 - 0.997, P < 0.05). Age is positively correlated to LVDD (OR 0.884, 95%
      CI 0.811 - 0.964, P < 0.005). The gammaglobulin level is significantly higher in
      the PAH group than that in the non-PAH group (P < 0.05). CONCLUSIONS: Cardiac
      involvement is not rare in patients with Sjogren syndrome. PE, LVDD and PAH are
      usual cardiac manifestations in these patients. The serum level of CRP is
      positively related to PE in these patients with Sjogren syndrome.

PMID- 19100011
TI  - [Myocardial expression and distribution of calcineurin in normal and failing
      human ventricular myocardium].
AB  - OBJECTIVE: To explore the expression and distribution of calcineurin (CaN) in
      normal and failing human myocardium. METHODS: Left and right ventricles were
      obtained from end-staged heart failure patients (n = 12) undergoing heart
      transplantation and donor hearts (n = 5) taken from victims of vehicle accidents.
      Immunohistochemistry and SDS-PAGE technique were used to demonstrate expression
      and distribution of CaN. RESULTS: Positive immunoreactive staining for CaN was
      detected in human cardiomyocytes, cardiac fibroblasts and epicardial mesothelial
      cells, but not detected in cardiac vascular endothelial cells and smooth muscle
      cells. There was no difference in CaN protein levels between failing hearts and
      donor hearts (Band intensity of right ventricle in failing hearts and donor
      hearts was 130.20 +/- 8.66 and 139.87 +/- 6.21, P = 0.33. Band intensity of left
      ventricle in failing hearts and donor hearts was 106.45 and 126.34 +/- 12.09) and
      between left ventricular and right ventricular myocardium (Band intensity of left
      and right ventricles in failing hearts was 96.99 +/- 10.67 and 104.58 +/- 13.18,
      P = 0.63. Band intensity of left and right ventricles in failing hearts was
      132.12 and 120.74). CONCLUSIONS: CaN is expressed in human cardiomyocytes,
      fibroblasts and epicardial mesothelial cells and the protein level and
      distribution of CaN are similar in failing and donor hearts.

PMID- 19100012
TI  - [Tongxinluo improves vascular endothelial function in patients with type 2
      diabetes].
AB  - OBJECTIVE: To investigate the effects of Tongxinluo on vascular endothelial
      function in patients with type 2 diabetes. METHODS: A total of 80 patients with
      type 2 diabetes were recruited and divided into two groups: Tongxinluo therapy
      group (n = 40) and conventional therapy group (n = 40). Plasma levels of NO, ET,
      6-keto-PGF1alpha and TXB2 and diastolic functions of humeral arteries (measured
      by high-resolution ultrasound) were measured at baseline and 4 weeks later.
      RESULTS: The flow-mediated dilation was significantly increased from (8.19 +/-
      0.71)% to (12.47 +/- 0.98)% (P < 0.05) in Tongxinluo therapy group after 4 weeks
      therapy compare to baseline level. Their plasma NO was significantly increased
      [(47.65 +/- 4.38) pg/ml to (52.91 +/- 4.83) pg/ml, P < 0.001] and plasma ET
      significantly reduced [(31.23 +/- 2.46) pg/ml to (24.34 +/- 2.46) pg/ml, P <
      0.001] post 4 week Tongxinluo therapy. Parameters remained unchanged in the
      placebo group (P > 0.05) at baseline and 4 weeks later. Non-flow-mediated
      dilation was unaffected by Tongxinluo therapy. CONCLUSIONS: Tongxinluo improved
      the vascular endothelial dependent diastolic function in patients with type 2
      diabetes by regulating the balance of plasma NO/ET.

PMID- 19100015
TI  - [Myocardial polyamine metabolism and the ischemia-reperfusion injury in the rat
      heart].
AB  - OBJECTIVE: To observe the polyamines metabolism changes in rat cardiomyocytes
      underwent ischemia-reperfusion (I/R) injury. METHODS: A branch of the descending
      left coronary artery was occluded to induce rat myocardial I/R injury (30 min
      ischemia followed by 2 h, 6 h, 12 h, and 24 h reperfusion). RT-PCR and Western
      blot were performed to detect the expression of spermidine/spermine N1
      acetyltransferase (SSAT) and ornithine decarboxylase (ODC), the concentrations of
      polyamines were measured with high performance liquid chromatography in hearts
      with or without I/R. RESULTS: The myocardial transcription and expression of SSAT
      and ODC were significantly upregulated. Compared with the sham group, ODC mRNA
      and SSAT mRNA respectively increased 3.1 fold and 3.8 fold and their proteins
      respectively increased 3.1 fold and 2.9 fold at 24 h of reperfusion (P < 0.01);
      the concentrations of spermidine, spermine and the total polyamine pool
      respectively decreased by 33.6%, 35.3% and 32.9% while putrescine concentration
      increased by 58.9% at 24 h of reperfusion (P < 0.01). CONCLUSION: Our results
      suggest that ischemia-reperfusion in the heart may affect polyamine metabolism
      and the disturbance of polyamine metabolism might thus play a critical role in
      myocardial I/R injury in this model.

PMID- 19100016
TI  - [Effects of perindopril and enalapril on atherosclerosis development of
      apolipoprotein E knockout mice].
AB  - OBJECTIVE: To compare the effects of perindopril and enalapril on the development
      of atherosclerotic lesions in ApoE knockout mice. METHODS: ApoE knockout mice
      were treated with perindoprilor (1.5 mg.kg(-1).d(-1), n = 20), enalapril (7.5
      mg.kg(-1).d(-1), n = 20) or saline (0.2 ml saline/d, n = 20) per gavage for 20
      weeks. Blood pressure and lipids were measured at the study end. Aortic root
      atherosclerotic plaque was then quantified and the content of collagen and the
      size of lipid core in the plaque assessed. Cryostat sections were used to
      quantify the expressions of monocyte/macrophage-2 (MOMA-2), intercellular
      adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1) and
      matrix metalloproteinases-9 (MMP-9) in the plaque by immunofluorescence method.
      RESULTS: Blood pressure and lipid profiles were similar among different groups.
      Compared with control group, the plaque areas of perindopril group and enalapril
      group displayed significantly decrease (25.33% and 22.86%, respectively, both P <
      0.01). However, no significant different were observed in the plaque size between
      the different ACE inhibitors groups. Perindopril group and enalapril group also
      significantly decreased the size of lipid core (52.98% and 38.98%, respectively,
      both P < 0.01) and the expression of MOMA-2 (88.38% and 52.16%, respectively,
      both P < 0.01), ICAM-1 (80.87% and 49.59%, respectively, both P < 0.01), VCAM-1
      (77.56% and 56.44%, respectively, both P < 0.01) and MMP-9 (86.93% and 55.56%,
      respectively, both P < 0.01), and increased the plaque collagen content (298.36%
      and 168.14%, respectively, both P < 0.01) and the effects of perindopril was
      superior to those of enalapril (all P < 0.05). CONCLUSIONS: ACE inhibitors
      significantly suppressed tissue inflammation and attenuated the development of
      atherosclerosis in ApoE knockout mice independent of their effects on the lipid
      and blood pressure. Perindopril is superior to enalapril in stabilizing the
      plaques and has similar effect on reducing the plaque size as that of enalapril.

PMID- 19100017
TI  - [Transmural heterogeneity of calcium handling proteins in the mechanism of
      porcine model of ventricular fibrillation].
AB  - OBJECTIVE: To investigate the role of heterogeneous expression of calcium
      handling proteins and spatial heterogeneity of APD restitution in the maintenance
      mechanism of ventricular fibrillation. METHODS: During programmed electrical
      simulation, APD restitution curves in the endocardium and epicardium of LV were
      constructed by plotting APD100 and diastolic interval. APD alternans, delayed
      after depolarization events were recorded simultaneously. Endocardial and
      epicardial myocytes were isolated from LV base and apex. Real time-PCR and
      Western blotting were performed to determine the relative messenger RNA and
      protein expression levels of calcium handling proteins. RESULTS: The normal
      hearts have spatial heterogeneity of action potential restitution property and
      transmural heterogeneity of calcium handling proteins. The slopes of the APD
      restitution curve in the endocardium were significantly steeper than those in
      epicardium, and the slopes of APD curve at the LV apex were significantly steeper
      than those in LV base. However, delayed after depolarization events with larger
      amplitude and earlier onset consistently occurred in the endocardium of LV base.
      After programmed electrical simulation, the expression of messenger RNA of RyR2,
      SERCA2a except for Calstabin2 significantly decreased (by 57% and 41%,
      respectively, P < 0.05) in the endocardium of the base, while the expression of
      RyR2, SERCA2a, Calstabin2 significantly increased (by 90%, 78%and 64%,
      respectively, P < 0.05) in the epicardium of LV base. Although transmural
      heterogeneity of calcium handling proteins at the LV apex were also observed
      after rapid pacing, there is no significant differences in the transmural
      heterogeneity at the LV apex compared to the LV base. The base of LV has unique
      calcium handling properties. CONCLUSIONS: It has been shown that Calcium cycling
      could modulate APD restitution property in the intact heart. The interaction
      between action potential and calcium dynamics instabilities is one of the most
      important reasons why simple criterion such as the APD restitution slope > 1 may
      fail to accurately predict the onset of APD alternans.

PMID- 19100018
TI  - [Quantitative evaluation of myocardial perfusion and regional systolic function
      by myocardial contrast stress echocardiography with computer-assisted technique
      in ischemic myocardium of rabbits].
AB  - OBJECTIVE: To evaluate the feasibility and value of determining myocardial
      perfusion and regional systolic function by myocardial contrast stress
      echocardiography (MCSE) with computer-assisted technique in a rabbit model of
      ischemia/reperfusion injury. METHODS: Rabbits underwent 30-(Group I, n = 15) and
      120-(Group II, n = 15) minute left ventricular branch of the left circumflex
      coronary artery occlusion foll owed by 60-minute reperfusion, dobutamine at
      increasing doses (5, 10, 15 and 20 microg.kg(-1).min(-1)) was then infused after
      reperfusion for 15 min. Bolus myocardial contrast agent was injected and MCSE
      performed at baseline, at the end of coronary occlusion and reperfusion, at the
      end of each dobutamine infusion. Images were analyzed by computer-assisted
      technique and myocardial calibrated contrast intensity (CI) of each segment was
      measured and a color-coded map was then obtained automatically (yellow: from 0 to
      -20 pix, blue:from -21 to -40 pix, green: from -41 to -70 pix, red: < -70 pix).
      The area at risk and infarct area obtained by red-coded map were compared with ex
      vivo results determined by fluorescent microsphere and triphenyl-tetrazolium
      chloride (TTC) staining. Percentage wall thickening (WT) of each risk segment at
      each stage were also measured. RESULTS: (1) During occlusion, WT in the areas at
      risk decreased to zero or negative and the calibrated CI values were
      significantly lower than those at baseline. Area at risk obtained by red-coded
      map correlated well with that obtained by fluorescent staining (r = 0.91, P <
      0.01). (2) After reperfusion and 5 microg.kg(-1).min(-1) dobutamine
      administration, WT and calibrated CI in all rabbits remained depressed.
      Calibrated CI at -70 pix was an optimal cutoff point to identify infarcted
      segments (sensitivity 95%, specificity 87%). The correlation between the infarct
      size by red-coded image and TTC was 0.89 (P < 0.01). (3) Calibrated CI and WT
      significantly improved in Group I rabbits while these parameters remained
      unchanged in Group II rabbits after increasing doses of dobutamine post ischemia.
      CONCLUSIONS: Myocardial contrast stress echocardiography in combination with
      computer-assisted analysis technique are valuable techniques to quantitatively
      assess myocardial perfusion and regional systolic function and exactly identify
      stunned myocardium and infarcted myocardium.

PMID- 19100023
TI  - [The progress in stress-induced cardiomyopathy].

PMID- 19100024
TI  - [ARC and cardiac myocyte apoptosis].

PMID- 19100026
TI  - [Atrial 11beta-hydroxysteroid dehydrogenase type 2 expression in rheumatic heart
      disease patients with or without atrial fibrillation].
AB  - OBJECTIVE: To investigate the mRNA and protein expressions of 11beta
      Hydroxysteroid dehydrogenase type 2 (11betaHSD2) in patients with atrial
      fibrillation. METHODS: Right and left atrial lateral wall tissue samples were
      obtained during mitral/aortic valve replacement operation from 25 patients with
      rheumatic heart valve disease (12 in sinus rhythm and 13 in chronic atrial
      fibrillation). Realtime quantitative PCR and Western blot were used to determine
      the mRNA and protein expressions of 11betaHSD2 in atria specimens. The
      distribution of 11betaHSD2 in human atrial tissue was analyzed by specific
      immunohistochemical staining. Echocardiography examination was performed before
      operation. RESULTS: The left atrial diameters were significantly higher in the
      atrial fibrillation group as compared to sinus rhythm group (P < 0.01).
      Similarly, mRNA expression of 11betaHSD2 (0.86 +/- 0.14 vs 0.33 +/- 0.12 in right
      atria, 0.95 +/- 0.15 vs 0.37 +/- 0.10 in left atria, all P < 0.01) and protein
      expression of 11betaHSD2 (1.18 +/- 0.64 vs 0.71 +/- 0.21 in right atria, P <
      0.01; and 1.36 +/- 0.58 vs 0.85 +/- 0.15 in left atria, P < 0.05) were also
      significantly upregulated in atrial fibrillation groups than those in sinus
      rhythm groups. The mRNA and protein expressions of 11betaHSD2 were similar
      between left atria and right atria both in fibrillation and sinus groups (all P >
      0.05). The special immunohistochemical staining demonstrated that 11betaHSD2 was
      abundant in the human atrial myocardium and located mainly in the cytoplasm.
      CONCLUSION: These findings suggested that upregulated 11betaHSD2 might be
      associated to the development and persistence of atrial fibrillation.

PMID- 19100027
TI  - [Comparison of peripheral blood hematopoietic progenitor cells among patients
      with paroxysmal, permanent atrial fibrillation or sinus rhythm].
AB  - OBJECTIVE: To compare peripheral blood hematopoietic progenitor cells (HPCs),
      plasma atrial natriuretic peptide (ANP) and stromal cell-derived factor-1alpha
      (SDF-1alpha) among patients with paroxysmal, permanent atrial fibrillation (AF)
      or sinus rhythm. METHODS: Peripheral blood concentration of CD34+HPCs were
      quantified by flow cytometric analysis (FCM), plasma ANP levels were measured by
      radioimmunoassay (RIA) method, plasma levels of SDF-1alpha were determined by
      enzyme linked immunosorbent assay (ELISA) in 30 patients with permanent AF, 28
      patients with paroxysmal AF, and 30 patients with sinus rhythm (SR). HPCs were
      separated, cultured and stained for ANP by the use of alkaline phosphatase-anti
      alkaline phosphatase technique (APAAP) in 30 patients (10 from each group).
      RESULTS: (1) The number of CD34+HPCs in permanent AF group [(5.31 +/- 1.67) x
      10(6)/L] were significantly higher comparing to paroxysmal AF group [(2.33 +/-
      1.29) x 10(6)/L] (P < 0.05) and SR group [(2.03 +/- 0.64) x 10(6)/L] (P < 0.05)
      while CD34+HPCs was similar between paroxysmal AF group and SR group (P > 0.05).
      (2) Plasma levels of ANP (0.312 +/- 0.121) microg/L and SDF-1alpha (3210.2 +/-
      1234.7) ng/L were also significantly higher in permanent AF group than paroxysmal
      AF group and SR group (all P < 0.05) and were similar in paroxysmal AF group and
      SR group (all P > 0.05). (3) The plasma levels of ANP and SDF-1alpha were both
      positive correlated with peripheral blood concentration of CD34+HPCs (r = 0.783,
      P < 0.01; r = 0.427, P < 0.01). (4) After 3 days of culture, ANP was weakly
      expressed in HPCs from patients with permanent AF but not from patients with
      paroxysmal AF and SR. CONCLUSIONS: Peripheral blood HPCs together with plasma ANP
      and SDF-1alpha were significantly increased in patients with permanent AF.
      CD34+HPCs were positive correlated with the plasma levels of ANP and SDF-1alpha.

PMID- 19100028
TI  - [Thoracoscopy video assisted minimally invasive bilateral pulmonary vein
      isolation for treatment of atrial fibrillation].
AB  - OBJECTIVE: This study is to evaluate the feasibility and safety of thoracoscopy
      video assisted minimally invasive bilateral pulmonary vein isolation for
      treatment of atrial fibrillation. METHODS: From December 2006 to April 2007,
      thorascopy video assisted off-pump epicardial pulmonary vein isolation was
      performed in 20 patients with atrial fibrillation. All patients were either
      refractory or intolerant to antiarrhythmic drug therapy or already experienced
      unsuccessful catheter-based ablation. The procedure includes 21 cm ports for the
      thoracoscopic camera and ablation device, and a 5 cm working port on each side of
      the chest wall. Bilaterally pulmonary vine were isolated by using an stricure(TM)
      bipolar radiofrequency device. LAA was removed by using a Johnson & Johnson EZ45G
      stapler. Intraoperative pacing and sensing was used to confirm bidirectional
      block of the ablation lines. RESULTS: The procedure was successful in all
      patients. Nineteen patients were in sinus rhythm immediately after the surgery
      and 1 patient was still in AF rhythm post surgery and converted to sinus rhythm
      by electrical conversion in the operation room. One patient was reintubated
      because of low SaO2 and 1 patient received IABP for LV failure. Mean operation
      time was (130 +/- 25) min and average hospital stay was (8.0 +/- 3.8) d. 3-months
      follow up was finished in 12 patients at after the surgery and 10 patients were
      free of AF (10/12, 83.3%), 6-months follow up was finished in 3 patients and all
      in sinus rhythm (3/3, 100%). CONCLUSION: Our results suggested that thoracoscopy
      video assisted minimally invasive bilateral pulmonary vein isolation is a safe,
      feasible and effective technique for treatment of atrial fibrillation.

PMID- 19100032
TI  - [Detection of gene mutations of SCN5A in 7 patients with Brugada syndrome].
AB  - OBJECTIVE: Brugada syndrome is linked to sodium channel mutations and could
      induce arrhythmias that even lead to sudden death. The purpose of this study was
      to detect if there was gene mutation of SCN5A in 7 patients with Brugada syndrome
      and explore the molecular genetic characteristics of this disease. METHOD:
      Genomic DNA was extracted from peripheral blood of all 7 patients with Brugada
      syndrome and 41 pairs of PCR primers were designed to amplify all the 28 exons of
      SCN5A. RESULT: There was no novel mutation in exons of Gene SCN5A in these
      patients with Brugada syndrome. CONCLUSION: Brugada syndrome might associated
      gene mutation or other mechanisms independent of SCN5A gene mutation.

PMID- 19100033
TI  - [Factors associated with reduced renal function post primary percutaneous
      coronary intervention in acute myocardial infarction patients with normal
      baseline serum creatinine level].
AB  - OBJECTIVE: To analyze factors associated with reduced renal function post primary
      percutaneous coronary intervention (PCI) in acute myocardial infarction (AMI)
      patients with normal baseline serum creatinine level. METHOD: The clinical and
      angiographic data of 216 consecutive AMI patients undergoing primary PCI with
      normal baseline serum creatinine level (< 1.5 mg/dl) were obtained and compared
      between patients with (n = 32) and without (n = 184) renal function deterioration
      (increase in serum creatinine > or = 25% from baseline level within 72 hours of
      primary PCI) post PCI. RESULTS: The incidence of renal function deterioration was
      14.8% (32/216). Patients with age > 75 years (28.1% vs. 14.1%, P = 0.047),
      congestive heart failure (25.0% vs. 9.2%, P = 0.017), less use of low-molecular
      weight heparins (84.4% vs. 95.1%, P = 0.039) and beta-blockers (75.0% vs. 95.6%,
      P = 0.001) as well as angiotensin converting enzyme inhibitors/angiotensin
      receptor blockers (81.3% vs. 93.5%, P = 0.025) and statins (84.4% vs. 97.3%, P =
      0.008) were risk factors for developing renal dysfunction post PCI. Renal
      function deterioration post PCI was also associated with increased in-hospital
      mortality (25.0% vs. 2.2%, P < 0.001). Multivariate analysis showed that
      congestive heart failure was the single independent predictor of renal function
      deterioration (odds ratio = 3.275, 95% confidence interval 1.275 - 8.408, P =
      0.014), while renal function deterioration was the strongest independent
      predictor of in-hospital death (odds ratio = 10.313, 95% confidence interval
      2.569 - 41.402, P = 0.001). CONCLUSION: Renal function deterioration is a common
      complication post primary PCI and is associated with higher risk of in-hospital
      death in AMI patients with normal baseline serum creatinine level.

PMID- 19100034
TI  - [Dobutamine stress echocardiography in patients with hypertrophic
      cardiomyopathy].
AB  - OBJECTIVE: To evaluate the safety and efficiency of the dobutamine stress
      echocardiography in patients with hypertrophic cardiomyopathy and estimate the
      difference between provokable obstruction and resting obstruction in these
      patients. METHODS: Echocardiography was performed in 22 patients with HCM (LVOTPG
      < 50 mm Hg at rest, 1 mm Hg = 0.133 kPa) at rest and at the end point of
      dobutamine stress. Dobutamine was administered via an infusion pump, starting at
      a dose of 5 microg x min(-1) x kg(-1) and increasing every 5 minutes by 5 microg
      x min(-1) x kg(-1) till the maximum dose of 20 microg x min(-1) x kg(-1). Fifty
      seven patients with HCM (LVOTPG > 50 mm Hg at rest) were also studied at rest.
      RESULTS: In these 22 patients, the mean maximum velocity of LVOT was 5.39 +/-
      1.60 m/s, the mean maximum LVOTPG was 125.7 +/- 62.4 mm Hg at the end point of
      dobutamine stress and the mean dose of dobutamine was 13.90 +/- 6.85 microg x
      min(-1)xkg(-1). Sixteen patients evidenced positive stress results at the end
      point of dobutamine stress. The main difference between the provokable
      obstruction and resting obstruction was that in provokable obstruction patients,
      the SAM positive patients were fewer and the proportion of Maron II patients was
      higher (50%). CONCLUSIONS: Dobutamine stress echocardiography was a safe and
      sensitive way for detecting patients with hypertrophic cardiomyopathy. Provokable
      obstruction patients had fewer SAM and higher proportion of Maron II.

PMID- 19100035
TI  - [Gender-related difference in patients with aortic dissection from Guangzhou].
AB  - OBJECTIVE: To investigate gender-related differences in risk factors, clinical
      manifestation and outcomes in patients with aortic dissection (AD) from
      Guangzhou. METHODS: Consecutive patients with AD admitted to our institute over
      the past 10 years were included in this retrospective analysis. Prevalence of
      hypertension, smoking, thickness of intraventricular septum and left ventricular
      posterior wall measured by echocardiography, and outcomes were compared between
      male and female AD patients. RESULTS: There were more male AD patients than
      female AD patients (5.33:1) from the 418 patients. Prevalence of hypertension,
      thickness of intraventricular septum and left ventricular posterior wall were
      similar in male and female AD patients. Heavy smoking history was 56.5% in males
      and 13.6% in females (P = 0.000). Acute survival rate in female patients tended
      to be better than that in male patients. CONCLUSIONS: There were significantly
      more male AD patients than female AD patients in this cohort. Prevalence of heave
      smoking in male patients is 3 times higher than that in female population.

PMID- 19100036
TI  - [Mentality and behavior of children with congenital heart diseases].
AB  - OBJECTIVE: The present study was designed to investigate the influence of
      Congenital Heart Disease (CHD) on the mentality and behavior in children, and to
      compare post operative mentality and behavior in children receiving
      interventional therapy and congenital heart surgery. METHOD: Mentality and
      behavior of 232 children suffering from CHD were examined with Achenbach Child
      Behavior Checklist (CBCL) edited by XU Tao-yuan in 1992 and 100 sex, age,
      education and achievement-matched children with pneumonia were enrolled as
      controls. RESULTS: The mentality and behavior abnormal rates of the boys and
      girls suffering from CHD were significantly higher than those of controls (P <
      0.01, P < 0.05). The behavior abnormities of the boys presented as depression,
      social flinch, physical complains, assault and violate rules. Whereas the girls
      presented as depression, social flinch, physical complains and violate rules. The
      total cursory mark of postoperative check result of the interventional and
      surgical children, both in girls and in boys, were significantly lower than those
      of the preoperative children (P < 0.05). The total and assault cursory mark of
      postoperative check result of children treated with interventional therapy were
      significantly lower than those of children treated with the surgical operations
      (P < 0.05). The abnormal rates of mentality and behavior positively correlated
      with the disease course. CONCLUSIONS: CHD is associated with increased abnormal
      mentality and behavior of the children. Early treatment, especially the
      interventional therapy can significantly improve the mentality and behavior of
      the children with CHD.

PMID- 19100038
TI  - [Effects of different amlodipine isomers on L-type calcium current of rat
      ventricular myocytes].
AB  - OBJECTIVE: To investigate the effects of different amlodipine isomers on L-type
      calcium current (ICa-L) and kinetics of rat ventricular myocytes. METHODS: Rat
      ventricular myocytes were isolated by enzyme digestion. ICa-L, peak currents, I-V
      curves, steady state activation curves, steady state inactivation curves and
      recovery curves from inactivation with S-amlodipine, R-amlodipine and R, S
      amlodipine at concentrations of 0.1, 0.5, 1, 5, and 10 micromol/L were recorded
      by whole-cell patch clamp configuration. RESULTS: At the concentrations of 0.1,
      0.5, 1, 5, and 10 micromol/L, ICa-L were blocked in a dose-dependent manner by S
      amlodipine [(1.5 +/- 0.2)%, (25.4 +/- 5.3)%, (65.2 +/- 7.3)%, (78.4 +/- 8.1)%,
      and (94.2 +/- 5.0)%] and by R, S-amlodipine [(0.9 +/- 0.1)%, (10.4 +/- 3.2)%,
      (69.1 +/- 5.3)%, (75.2 +/- 7.0)%, and (81.6 +/- 6.4)%]. I-V curves were
      significantly shifted upward, steady state activation and inactivation curves
      were significantly shifted to left by S-amlodipine and R, S-amlodipine (0.1
      micromol/L to 10 micromol/L). Recovery time from inactivation was also
      significantly prolonged by S-amlodipine [(210.1 +/- 19.5) ms, (225.2 +/- 21.3)
      ms, (241.7 +/- 20.3) ms, (252.3 +/- 24.2) ms, and (282.6 +/- 23.2) ms] and by R,
      S-amlodipine [(208.7 +/- 17.4) ms, (215.8 +/- 18.3) ms, (225.2 +/- 21.3) ms,
      (235.8 +/- 22.7) ms, and (252.3 +/- 24.2) ms] in a dose-dependent manner. The
      observed effects of S-amlodipine were more potent than those of R, S-amlodipine
      (P < 0.05). However, all these parameters were not affected by R-amlodipine at
      various concentrations (P > 0.05). CONCLUSION: L-type calcium current of rat
      ventricular myocytes could be blocked by R, S-amlodipine and S-amlodipine in a
      dose-dependent manner.

PMID- 19100039
TI  - [Transient change of cardiac action potential and intracellular Ca2+ during
      ventricular fibrillation].
AB  - OBJECTIVE: The cardiac action potential (AP) and the intracellular Ca(2+)
      transient (CaT) are closely associated under normal physiological conditions, but
      not during ventricular fibrillation (VF). The purpose of this study was to
      determine whether this dissociation is directly related to the higher activation
      rate during VF. METHODS: We optically mapped AP and CaT simultaneously in nine
      isolated rabbit hearts. Pinacidil, a K(ATP) channel opener, was used to shorten
      the action potential duration (APD) in order to capture tissue at fast pacing
      rates or to induce ventricular tachycardia (VT) comparable to VF activation
      rates. Mutual information (MI) was used to calculate the degree of AP and CaT
      coupling. RESULTS: Pinacidil (40 micromol/L) infusion significantly shortened
      APD. The averaged cycle length (CL) of VF without Pinacidil was (77 +/- 13) ms,
      whereas the shortest CL achieved during VT under Pinacidil infusion was 76 ms.
      MIs during fast pacing (1.13 +/- 0.15) bits and fast VT (0.88 +/- 0.18) bits were
      higher than those during baseline VF (0.39 +/- 0.11) bits, VF with Pinacidil
      infusion (0.21 +/- 0.07) bits and VF after Pinacidil washout (0.36 +/- 0.15)
      bits. MIs during fast pacing or fast VT were higher than those of VFs at
      comparable dominant frequencies. CONCLUSIONS: CaT is closely associated with the
      AP during fast pacing and fast VT, but not during VF. The reduced MI during VF is
      not secondary to the fast rate of ventricular activation.

PMID- 19100040
TI  - [Emergency surgery combined with epicardial radiofrequency ablation for a patient
      with cardiac tamponade complicating catheter ablation for atrial fibrillation].

PMID- 19100041
TI  - [Effects of C-reactive protein on bone marrow-derived endothelial progenitor cell
      function].
AB  - OBJECTIVE: To observe the effects of C reactive protein (CRP) on endothelial
      progenitor cell (EPCs) function. METHODS: Mononuclear cells (MNCs), isolated from
      bone marrow by density gradient centrifugation combined with adherent cell
      filtration, were plated on fibronectin coated culture dishes. After 7 days,
      adherent cells were cultured with different concentrations of CRP (0, 5, 10, 15,
      20 microg/ml) for 48 hours. EPCs proliferation and migration ability were
      observed and adhesion assay was performed. The eNOS mRNA expression of EPCs were
      measured by RT-PCR. RESULTS: The number of EPCs in CRP groups (10, 15,
      20microg/ml) was obviously lower than that in control group (54 +/- 3, 47 +/- 3,
      39 +/- 5 vs.60 +/- 3, P < 0.01). EPCs proliferation capacity was inhibited in CRP
      groups (10, 15, 20 microg/ml) compared with that in control group (0.297 +/-
      0.036, 0.273 +/- 0.013, 0.259 +/- 0.035 vs. 0.345 +/- 0.014, P < 0.01). EPCs
      migration capacity was inhibited significantly in CRP groups (5, 10, 15, 20
      microg/ml) than that in control group (28 +/- 2, 22 +/- 3, 19 +/- 3, 16 +/- 2 vs.
      30 +/- 2, P < 0.05). EPCs adhensive number was lower in CRP groups than that in
      control group (11 +/- 2, 9 +/- 2, 6 +/- 2, 5 +/- 1 vs. 12 +/- 2, P < 0.05). The
      mRNA expressions of eNOS in CRP groups were significantly lower in control group.
      And compared with control group, NOS activity decreased significantly in CRP
      groups (10, 15, 20 microg/ml) (57.44 +/- 3.25, 48.37 +/- 3.86, 36.82 +/- 4.89 vs.
      68.56 +/- 2.82, P < 0.01). CONCLUSION: CRP could both reduce EPCs number and
      inhibit EPCs functions.

PMID- 19100042
TI  - [Parathyroid hormone 1-34 induce cardiac myocytes hypertrophy via extracellular
      regulated protein kinase 1/2 pathway].
AB  - OBJECTIVE: To investigate the role of mitogen activated protein kinase kinase 1
      (MAPKK, MEK1) and regulated kinase1/2 (ERK1/2) on cardiac hypertrophy induced by
      rat parathyroid hormone1-34 (rPTH1-34). METHOD: Neonatal rat cardiomyocytes was
      treated with or without 10(-7) mol/L rPTH1-34 in the absence or presence 2 x 10(
      5) mol/L PD98059, a MEK1 inhibitor. Cellular diameter was measured by Motic
      Images Advanced 3.0 software and the synthetic rate of protein in cardiac
      myocytes was detected by 3H-leucine incorporation, mRNA expression of atrial
      natriuretic peptide (ANP) was measured by RT-PCR and protein expression of ERK1/2
      and p-ERK1/2 was measured by Western blot. RESULTS: rPTH1-34 (10(-7) mol/L)
      significantly increase cellular diameter (+13.6 microm), 3H-leucine incorporation
      (+898 cpm/well), ANP mRNA expression (+73.9%), and p-ERK1/2 protein expression
      (+15%) compared to control cells (all P < 0.05) and these effects could be
      significantly attenuated by PD98059: cellular diameter (-7.1 microm), 3H-leucin e
      incorporation (-644 cpm/well), ANP mRNA expression (-52.2%), and protein
      expression of p-ERK1/2 (-18%) (all P < 0.05 vs. PTH group). PD98059 did not
      affect control cells without PTH treatment (all P > 0.05). CONCLUSIONS: PD98059
      attenuates PTH induced cardiac hypertrophy in vitro via inhibiting the expression
      of ERK1/2 and p-ERK1/2.

PMID- 19100043
TI  - [AcSDKP attenuates PDGF-induced cardiac fibroblasts proliferation and collagen
      expression: role of extracellular regulated protein kinase 1/2 pathway].
AB  - OBJECTIVE: To investigate the effects of AcSDKP on platelet-derived growth factor
      (PDGF)-induced rat cardiac fibroblasts proliferation and collagen expression and
      explore the role of extracellular regulated protein kinase 1/2 (ERK1/2) pathway
      on this process. METHODS: Metabolic activity of fibroblasts was determined by CCK
      8. Cell cycle was detected by flow cytometry. 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. RESULT: 10(-9) mol/L
      AcSDKP could significantly inhibit PDGF-induced cardiac fibroblasts
      proliferation, collagen expression and expressions of phospho-ERK1/2, while the
      protein levels of ERK1/2 were not significantly affected by AcSDKP. CONCLUSION:
      AcSDKP could inhibit PDGF-induced cardiac fibroblasts proliferation and collagen
      expression through activation of phosphor-ERK1/2 pathway.

PMID- 19100045
TI  - [The association between white blood cell count and 10-year cardiovascular risk
      in a large Chinese cohort aged 35-64 years].
AB  - OBJECTIVE: To evaluate the association between white blood cell count and the
      risk of cardiovascular diseases (CVD) in subjects aged 35 - 64 years. METHODS:
      This prospective study was carried out in 11 provinces from 1992 to 2003. The
      association of baseline white blood cell count and cardiovascular disease
      occurrence was analyzed in 30 384 subjects aged 35 - 64 years using Cox
      multivariate proportional hazards regression. RESULTS: (1) Compared with the
      group of 4.0 - 4.9 x 10(9)/L, multivariate-adjusted relative risk of ischemic
      cardiovascular disease (ICVD, including coronary heart disease and ischemic
      stroke) increased continuously in proportion to increased white blood cell count.
      (2) White blood cell count had different impact on different types of CVD.
      Positive association was observed between white blood cell count and the risk of
      ischemic stroke, but the relationship between white blood cell count and the risk
      of hemorrhagic stroke was not significant. Compared with the referent group (4.0 
      4.9 x 10(9)/L), the risk of coronary heart disease of the group of white blood
      count > 9.0 x 10(9)/L increased by 70% (RR = 1.71, P < 0.05) and that of ischemic
      stroke increased by 80% (RR = 1.85, P < 0.01). CONCLUSION: The risk of ICVD and
      CVD increases continuously in proportion to increased white blood cell count, the
      white blood cell count might be used to predict future risk of CVD, especially
      risk for ICVD.

PMID- 19100046
TI  - [Prevalence of hypertension in the Guangxi Bai Ku Yao populations].
AB  - OBJECTIVE: To observe the prevalence of hypertension and associated risk factors
      in the Guangxi Bai Ku Yao populations. METHODS: A total of 1170 subjects of Bai
      Ku Yao aged 15 and over were surveyed by a stratified randomized cluster
      sampling. Blood pressure, body height, weight, waist circumference, serum lipid
      and apolipoprotein levels were measured, and body mass index (BMI) were
      calculated, matched 1173 subjects of Han Chinese from the same region served as
      control. RESULTS: The standardized prevalence of hypertension in Bai Ku Yao was
      significantly lower than that in Han (11.53% vs.16.79%, P < 0.01). The mean
      levels of systolic, diastolic blood pressure, and pulse pressure in Bai Ku Yao
      were also significantly lower than those in Han [(115.7 +/- 16.3) vs. (120.0 +/-
      16.3) mm Hg (1 mm Hg = 0.133 kPa), P < 0.01; (74.1 +/- 9.4) vs. (75.9 +/- 10.4)
      mm Hg, P < 0.01; and (41.6 +/- 12.0) vs. (44.2 +/- 11.2) mm Hg, P < 0.01;
      respectively]. Hypertension was positively correlated with male, age, physical
      activity, BMI, waist circumference, and the intakes of total energy, total fat,
      and sodium, and negatively associated with education level in both ethnic groups
      (P < 0.05 - 0.01), but was positively associated with alcohol consumption only in
      Han. The rates of awareness, treatment and control of hypertension were
      significantly lower in Bai Ku Yao than those in Han population [(11.81% vs.
      21.76%), P < 0.05; (5.51% vs. 12.95%), P < 0.05; and (2.36% vs. 8.29%), P < 0.05;
      respectively]. CONCLUSION: The prevalence of hypertension was significantly lower
      in Bai Ku Yao population than in Han population and diet, low sodium intake, life
      style, and genetic factors might be responsible for the lower hypertension
      prevalence in Bai Ku Yao population.

PMID- 19100047
TI  - [Acute amiodarone-induced hepatotoxicity in a patient].

PMID- 19100048
TI  - [Two cases of ventricular noncompaction myocardium with preexcitation syndrome].

PMID- 19100049
TI  - [Coalesce at outlet of multiple coronary artery fistulae: two cases report
      treated by intervention].

PMID- 19100050
TI  - [Acute inferior myocardial infarction due to type A aortic dissection: a case
      report].

PMID- 19100051
TI  - [Massive retroperitoneal hematoma during enoxaparin combined with aspirin
      treatment of acute pulmonary embolism: a case report].

PMID- 19100052
TI  - [Association between osteopontin and restenosis].

PMID- 19100053
TI  - [Proteomics in heart disease research].

PMID- 19100055
TI  - [Intravascular ultrasonic evaluation of poststenting atherosclerotic plaque
      redistribution and lumen reduction at the stent edge: does stent length matter?].
AB  - OBJECTIVE: To evaluate the association between poststenting atherosclerotic
      plaque redistribution/lumen reduction at the stent edge and stent length.
      METHODS: Seventy stents were implanted to 47 patients with stable or unstable
      angina and 33 stents were < or = 18 mm and 37 stents were > 18 mm. Intravascular
      ultrasound analysis was performed on proximal stent edge, stent area and distal
      stent edge. Lumen area (LA) and vascular area (VA) were measured and lumen volume
      (LV) and vascular volume (VV) were calculated on the three segments. Vascular
      wall volume (WV) was calculated as VV-LV, volume of plaque redistribution =
      poststenting WV-prestenting WV. RESULTS: Compared to prestenting, poststenting LV
      significantly decreased, VV remained unchanged and WV significantly increased at
      proximal and distal edges of < or = 18 mm group and at proximal edge of > 18 mm
      group, suggesting reduced lumen due to plaque distribution. At distal edge of >
      18 mm group, poststenting LV, VV and WV all equally significantly increased
      therefore the lumen was not affected by plaque distribution. CONCLUSION: The
      poststenting lumen changes due to plaque redistribution were associated with
      stent length, lumen reduced at proximal and distal edge of short stents and
      proximal edge of long stents but not at the distal edge of long stents.

PMID- 19100056
TI  - [The safety and outcome of patients with acute myocardial infarction transferred
      for primary angioplasty].
AB  - OBJECTIVE: To evaluate the safety and outcome of patients with acute myocardial
      infarction (AMI) transferred for primary percutaneous coronary intervention
      (PCI). METHODS: Data from patients with ST elevation AMI urgently transferred
      from first admitted hospitals to our cath-lab to receive primary PCI were
      analyzed. According to time intervals from symptom onset to transfer, the
      patients were divided into early transfer (< 6 h, n = 26), delayed transfer (6 -
      24 h, n = 39) and late transfer (24 h to 1 week, n = 18) group. The major cardiac
      events during transfer periods and one month after PCI were obtained and
      echocardiogram and left ventricular systolic functions were compared among
      groups. RESULTS: There was no serious cardiac event during transfer period and
      all 83 patients received primary PCI with a mean transfer-to-balloon time about
      180 minutes. Success rate of PCI was 92.3% in early transfer group, 89.7% in
      delayed transfer group, and 94.4% in late transfer group (P > 0.05). At one month
      follow-up after PCI, 0, 10.3% and 16.7% of patients developed heart failure in
      early, delayed transfer and late transfer group respectively (P > 0.05 vs.
      early), the LVEF of early transfer group (53.2% +/- 9.7%) was also significantly
      higher than delayed transfer group (48.6% +/- 8.2%, P < 0.05) and late transfer
      group (43.1% +/- 10.3%, P < 0.01). CONCLUSIONS: Transfer patients with AMI for
      primary PCI is safe in the observed time intervals during acute phase. Early
      transferred patients are associated with better outcome at 1 month post PCI
      compared to delayed and late transferred AMI patients.

PMID- 19100057
TI  - [Effects of transcatheter closure of extracardiac Fontan fenestration by
      Amplatzer duct or septal occluder in three patients].
AB  - OBJECTIVE: The purpose of this study was to report our experiences from the
      transcatheter closure of patent fenestration after total cavopulmonary connection
      (TCPC) with an extra cardiac conduit. METHODS: Three patients (7, 14 and 8 years
      old) with various forms of functionally univentricular heart lesions received a
      total cavopulmonary connection with an extra cardiac conduit as a final
      reconstructive procedure. Transcatheter occlusion of the fenestration was
      accomplished using a 8/6 mm Amplatzer duct occluder in one patient, and 5 mm or
      10 mm Amplatzer septal occluder in the other two patients. Residual shunting
      following occlusion was assessed using angiography and echocardiography. RESULTS:
      Post total cavopulmonary connection with an extra cardiac conduit, diagnostic
      catheterization revealed normal pressures in the superior vena cava and pulmonary
      artery without obstruction at the site of the anastomosis. Angiography of the
      extra cardiac conduit confirmed the communication between the conduit and the
      atrium in all three patients and patients still suffered from cyanosis and low
      oxygen saturation. Immediate full occlusion of fenestration was obtained in all
      patients. Post closure, mean central venous pressure returned to normal
      accompanied with significantly increased oxygen saturation. Cyanosis was also
      significantly attenuated. There were no procedural complications or device
      failures at intra-hospital and during the 3 to 6 months follow up period.
      CONCLUSIONS: The Amplatzer septal or duct occluder device is a safe and effective
      strategy for the Fontan fenestration occlusion.

PMID- 19100058
TI  - [Efficacy comparison with low and high dose nadroparin for patients with acute
      coronary syndrome underwent percutaneous coronary intervention].
AB  - OBJECTIVE: To evaluate the safety and optimal prior percutaneous coronary
      intervention (PCI) nadroparin dose in patients with acute coronary syndrome
      (ACS). METHODS: A total of 236 ACS patients were randomly treated with
      subcutaneously nadroparin 0.075 ml/10 kg (group I, n = 120) and 0.1 ml/10 kg
      (group II, n = 116) respectively (bid for 48 hours). PCI was the performed 1 h
      after final nadroparin injection. No additional nadroparin was applied during
      PCI. Plasmic anti-Xa level was assayed before and at 1, 2, 4 and 8 hours after
      final nadroparin administration. Adverse clinical events (death, myocardial
      infarction, need for revascularization) and bleeding events were recorded up to
      30 days post PCI. RESULTS: Baseline clinical characteristics as well as the MACE
      and severe bleeding events between the two groups were similar (all P > 0.05).
      Plasmic anti-Xa level of group II was significantly higher than that of group I
      post nadroparin application (P < 0.01). CONCLUSION: Anticoagulation effects and
      MACE as well as severe bleeding events up to 30 days post PCI were similar with
      either 0.075 ml/10 kg or 0.1 ml/10 kg nadroparin dose in ACS patients.

PMID- 19100059
TI  - [Side branch occlusion rate at sites of overlapping sirolimus- or paclitaxel
      eluting stents for treating long coronary lesions].
AB  - OBJECTIVE: To compare side branch occlusion rate at sites of overlapping
      sirolimus- or paclitaxel-eluting stents in treating long coronary lesions.
      METHODS: We retrospectively reviewed the PCI CD and medical records of PCI 141
      patients with at least one stent overlapping for long coronary lesion in our
      institute from January 2004 to October 2007. The side branches occlusion was
      documented and analyzed. RESULTS: The study population were consisted of 141
      patients that there were 115 man, and 26 women, who got 297 stents. There were
      154 side branch vessels been observed. Side branch occlusion rate was 24.6% in
      Cypher group and 31.6% in TAXUS (P > 0.05), side branch TIMI flow decrease rate
      on overlapping region was 26.3% in Cypher group and 68.4% in TAXUS group (P >
      0.05). A logistic regression model analysis show that the significant risk
      factors for side branch occlusion is the diameter and ostial occlusion of side
      branch. CONCLUSION: Side branch occlusion rate and TIMI flow decrease rate were
      similar on overlapping region in patients treated with Cypher or TAXUS stents for
      long coronary lesions. The significant predictors for side branch TIMI flow
      decrease are the diameter and ostial occlusion of side branch.

PMID- 19100060
TI  - [Association between single nucleotide polymorphisms of matrix metalloproteinase
      3 gene and the severity of coronary atherosclerosis in patients with coronary
      artery disease].
AB  - OBJECTIVE: To investigate the association between the severity of coronary
      arteries in patients with coronary artery disease and the single nucleotide
      polymorphisms of MMP-3 gene. METHODS: One thousand and three hundred seventy-one
      patients with coronary artery disease (CAD) diagnosed by coronary angiography and
      six hundred and ninety-five healthy controls without CAD were enrolled in this
      study. The SNPs of -1612 5A/6A, -376C/G, Glu45Lys of MMP-3 were genotyped by
      restriction fragment length polymorphism analysis (RFLP) in all subjects.
      Univariate analysis was applied to measure the association of the single
      nucleotide polymorphisms with the severity of coronary arteries. RESULTS: The
      minor allele frequency of -1612 5A/6A was 0.189, 0.185, 0.183 and 0.152 (P < 0.05
      vs. non-CAD control and single stenosis), the minor allele frequency of -376C/G
      was 0.311, 0.329, 0.326 and 0.325, and the minor allele frequency of Glu45Lys was
      0.367, 0.423, 0.417 and 0.405 in non-CAD control, CAD patients with single, two
      and three vessels stenosis, respectively. 5A allele frequency is significant
      lower in the group with three vessels stenosis than in non-CAD control and CAD
      patients with single vessel stenosis (OR = 0.74, P = 0.04). The 5A/5A and 5A/6A
      genotypes frequency is significant lower in the group with three vessels stenosis
      than in the non-CAD group and CAD patients with single vessel stenosis (OR =
      0.74, P = 0.04). CONCLUSIONS: The single nucleotide polymorphism of -1612 5A/6A
      of MMP-3 gene may be associated with the severity of coronary atherosclerosis in
      the Chinese Han patients with coronary artery disease, and the 5A allele might
      therefore, play a protective role on the progression of coronary atherosclerosis.

PMID- 19100061
TI  - [Analysis of heterogeneity in exon 4 of Coxsackievirus and Adenovirus receptor
      gene in dilated cardiomyopathy].
AB  - OBJECTIVE: To investigate the genetic pathogenesis of dilated cardiomyopathy
      (DCM) by examining the heterogeneity of Coxsackievirus binding domain (exon 4) of
      Adenovirus receptor (CAR) in DCM patients and healthy adults, and to detect
      possible mutation site in exon 4. METHODS: Using polymerase chain reaction (PCR),
      we amplified exon 4 of CAR DNA extracted from blood samples obtained from 50 DCM
      patients and 40 healthy adults. The PCR products were screened with single-strand
      conformation polymorphism (SSCP) and then sequenced alternatively based on the
      SSCP results. RESULTS: The segment of CAR exon 4 was successfully amplified and
      there was no single strand conformational disparity in all samples examined by
      SSCP. Sequence analysis demonstrated that all amplified sequences of CAR exon 4
      from samples of the two groups were identical and there was no genetic
      heterogeneity of CAR exon 4 between the two groups. CONCLUSION: The genetic
      heterogeneity of CAR exon 4 might not be responsible for the pathogenesis of DCM.

PMID- 19100063
TI  - [The relationship between the effect of amlodipine on carotid intimal-medial
      thickness and angiotensin converting enzyme genotypes in elderly hypertensive
      patients].
AB  - OBJECTIVE: To investigate the association between the anti-atherosclerotic
      effects of amlodipine and angiotensin converting enzyme (ACE) gene
      insertion/deletion (I/D) polymorphism in elderly essential hypertensive (EH)
      patients. METHODS: A total of 220 EH patients were treated with amlodipine (2.5 -
      10 mg, once daily) for twelve months and complete data were obtained from 208
      patients with genotypes of II (n = 90), ID (n = 91) and DD (n = 27). The indices
      of carotid arterial were compared before and post amlodipine treatment in
      patients with identical genotype and among different ACE genotypes and each
      genotype post therapy. RESULTS: The carotid mean intimal-medial thickness (MIMT)
      was slightly decreased in EH patients with ID and DD genotypes and significantly
      decreased in EH patients with II genotype (0.96 +/- 0.12 vs. 0.92 +/- 0.13, P <
      0.01) compared to pre-treatment values. The decreased degree of MIMT (DeltaMIMT)
      in II genotype was significantly higher in II genotype than those in ID or DD
      genotype (0.05 +/- 0.03 vs. 0.01 +/- 0.02, 0.01 +/- 0.03 respectively, P < 0.01).
      The post treatment plaque score (PS) in patients with II genotype was
      significantly reduced (4.85 +/- 2.51 vs. 3.90 +/- 2.36, P < 0.05). Multivariate
      linear regression analysis showed the baseline SBP, the decreased degree of SBP
      (DeltaSBP) and the II genotype were the major factors affecting the DeltaMIMT.
      CONCLUSION: Hypertensive patients carrying II genotype ACE genotype are the best
      responders for the anti-atherosclerotic effects of amlodipine.

PMID- 19100064
TI  - [Value of measuring ankle brachial index for diagnosing peripheral arterial
      disease in Chinese patients with high cardiovascular risk].
AB  - OBJECTIVE: To evaluate the value of measuring ankle brachial index (ABI) for
      diagnosing peripheral arterial disease(PAD) compared with conventional digital
      subtraction angiography (DSA) as the reference standard. METHODS: A total of 383
      consecutive inpatients (245 male, mean age 64.1 +/- 11.7 years) underwent both
      conventional DSA and ABI measurements. RESULTS: The rate of statin intervention
      was 90.9%, ACEI 69.2%, antiplatelet 96.6% and beta-blockers 67.9%. The
      intravascular stenosis was classified into six degrees: normal, < 30%, 30% - 49%,
      50% - 69%, 70% - 89% and > or = 90%. Compared to the traditional gold standard
      (DSA) in diagnosis PDA, the ABI value decreased in proportion to the severity of
      PAD (the ABI value was 1.08 +/- 0.11, 1.05 +/- 0.16, 0.99 +/- 0.17, 0.66 +/-
      0.24, 0.55 +/- 0.28 and 0.54 +/- 0.00 respectively in the six ranks). There was a
      significant correlation between DSA and ABI in diagnosis PAD. CONCLUSION: ABI
      measurement is an accurate and reliable non-invasive alternative to conventional
      DSA in the assessment of lower extremity arteries in patients with peripheral
      arterial disease.

PMID- 19100065
TI  - [Prognostic value of microvolt level T-wave alternans in patients at high risk of
      sudden cardiac death].
AB  - OBJECTIVE: To explore the predict value of microvolt level T-wave alternans
      (MTWA) for malignant ventricular arrhythmia (MVA) and sudden cardiac death (SCD)
      in high risk patients. METHODS: A total of 105 healthy subjects (control group)
      and 138 patients with history of VT or VF or patients with LVEF < or = 45% (SCD
      high risk group) were included in this study (mean age 52 years old). MTWA, LVEF,
      HRV, NSVT, QRS, QTc values and MACE data (death, causes of death, MVA, re
      hospitalization, syncope) during follow up (12.0 +/- 1.3) months were obtained.
      RESULTS: The normal reference value of MTWA was defined as < 37 microV. Positive
      rate in SCD high risk group was significantly higher than that in control group
      (45.7% vs. 4.8%, P < 0.01). There was no cardiovascular event report in control
      group. In SCD high risk group, there were 11 deaths (MTWA positive rate 81.8%)
      including 7 SCD (MTWA positive rate 85.7%), 17 MVA (MTWA positive rate 88.2%), 9
      cases of syncope (MTWA positive rate 77.8%), 21 cases of re-hospitalization
      during the follow up (MTWA positive rate 85.7%). Logistic regression analysis
      revealed that positive MTWA, a history of myocardial infarction and LVDd > or =
      60 mm were risk factors for all cause of death and positive MTWA was the only
      factor to predict SCD. The factors related to MVA in turn were positive MTWA,
      LVEF < or = 35%, a history of cardiopulmonary resuscitation and a history of
      syncope. Positive MTWA and LVEF < or = 35% are the independent risk factors for
      predicting MVA (P < 0.01). The sensitivity was 91% and specifity was 66% by
      combined use of positive MTWA and LVEF < or = 35% to predict MVA. MTWA positive
      rates were 68.3% and 87.5% respectively in 41 ICD patients and ICD patients with
      automatic shock during follow up. CONCLUSION: Non-invasive MTWA measurement could
      be used as a screening tool to predict SCD or MVA in high risk patients.

PMID- 19100066
TI  - [Serum uric acid prevalence and changes post various antihypertensive agents in
      patients with essential hypertension].
AB  - OBJECTIVE: To survey the prevalence of hyperuricacidemia and serum uric acid
      (SUA) changes and electrolyte changes after 6 weeks antihypertensive treatment
      with thiazide diuretics, losartan or losartan+hydrochlorothiazide (Hyzaar) in
      patients with essential hypertension (EH). METHODS: A total of 1080 consecutive
      EH patients [662 males, mean age (60.9 +/- 12.3) years] who seeked for medical
      consultation in study hospitals in Fuzhou city during October 2004 and October
      2006 were included in this study. The blood pressure before and after
      antihypertensive treatments were obtained in 1000 patients, and the renal
      function and electrolyte before and after antihypertensive treatments were
      obtained in 600 patients. Patients with SBP > 140 and/or DBP > 90 mm Hg 2 weeks
      after initial antihypertensive agents were cotreated with felodipine, patients
      with SBP > 140 and/or DBP > 90 mm Hg 4 weeks after initial antihypertensive
      agents were cotreated with beta and/or alpha blockers. RESULTS: The prevalence of
      hyperuricacidemia in EH patients was 25.83% (279/1080). Body mass index (BMI) and
      creatinine were significantly higher while creatinine clearance rate (Ccr)
      calculated by Cockcroft-Gault equation was significantly lower in EH patients
      with hyperuricacidemia than EH patients without hyperuricacidemia (all P < 0.05).
      Similar antihypertensive effects were observed in EH patients treated with
      thiazide diuretics (n = 200), losartan (n = 324) or losartan +
      hydrochlorothiazide (Hyzaar, n = 476) and SBP was lower than 140 mm Hg in 69.40%
      and DBP was less than 90 mmHg in 85.30% EH patients 6 weeks after
      antihypertensive treatments. SUA was significantly increased (43.81 micromol/L +/
      71.79 micromol/L) low dose diuretics group (P < 0.01 vs. pretreatment),
      significantly reduced (44.96 micromol/L +/- 90.63 micromol/L) in losartan group
      (P < 0.0001 vs. pretreatment) and remained unchanged in Hyzaar group (7.46 +/-
      84.72 micromol/L, P > 0.05 vs. pretreatment). Serum potassium was significantly
      decreased (0.30 +/- 0.44 mmol/L) in diuretic group (P < 0.01 vs. pretreatment)
      and remained unchanged in losartan group (+0.06 +/- 0.43 mmol/L) and Hyzaar group
      (-0.04 +/- 0.44 mmol/L, all P > 0.05 vs. pretreatment). CONCLUSION:
      Hyperuricacidemia prevalence was 25.83% and associated with higher BMI and
      abnormal renal function in examined EH patients. The low dose thiazide diuretics
      could further aggravate hyperuricacidemia and induce hypopotassemia while
      losartan could reduce hyperuricacidemia in EH patients.

PMID- 19100067
TI  - [The relation between positive rate of autoantibodies against beta1 and M2
      adrenergic receptors and urinary albumin excretion rate in the type 2 diabetes
      mellitus with refractory hypertension].
AB  - OBJECTIVE: To explore the relation between the positive rates of autoantibodies
      against beta(1) adrenergic receptor (beta1-receptor)and (M2-receptor) with
      urinary albumin excretion rate (UAER) in type 2 diabetes patients with refractory
      hypertension. METHODS: Autoantibodies against beta(1)- and M(2)-receptor as well
      as autoantibodies were determined in type 2 diabetes patients with (n = 136) or
      without (n = 111) refractory hypertension, hypertensive patients without renal
      failure (n = 60) and healthy control subjects (n = 40, control) by ELISA.
      RESULTS: The positive rates of the autoantibodies against beta1-receptors (44.9%)
      and M(2)-receptor (37.5%) in patients with type 2 diabetes with refractory
      hypertension were significantly higher than those in patients with type 2
      diabetes without refractory hypertension (27.9% and 24.3%, respectively, all P <
      0.05), in patients with hypertension without renal failure (11.7% and 15.0%, all
      P < 0.01) and in healthy controls (8.3% and 7.5%, all P < 0.01). In type 2
      diabetes patients with refractory hypertension and renal failure (UAER > or = 200
      microg/min), the positive rates of the autoantibodies against beta(1)-receptor
      (87.1%, 27/31) and against M(2)-receptor (67.7%, 21/31) were significantly higher
      than those in type 2 diabetes patients with refractory hypertension but without
      renal failure (UAER 20 - 199 microg /min, 46.7%, 28/60 and 41.7%, 25/60,
      respectively, all P < 0.05). CONCLUSION: The serum beta(1)- and M (2)-receptor
      autoantibodies are positively associated with the UAER level and suggest that
      these autoantibodies against beta(1) and M(2)-receptor may play important roles
      in the pathogenesis of the type 2 diabetes with refractory hypertension.

PMID- 19100068
TI  - [Clinical features in 65 patients with acute myocardial infarction underwent
      successful thrombolytic therapy post cardiopulmonary resuscitation].
AB  - OBJECTIVE: To analyze the clinical features of patients with acute myocardial
      infarction underwent successful thrombolytic therapy post cardiopulmonary
      resuscitation. METHODS: This retrospective analysis included 65 patients with
      acute myocardial infarction underwent successful intravenous thrombolysis post
      cardiopulmonary resuscitation. The cases were collected from Chinese Journal Full
      text Database from 1996 to 2006, only patients met the recanalization criteria of
      coronary artery were included. RESULTS: Most of the patients were male (93.8%,
      61/65) and aged less than 65 years (81.5%, 53/65). Cardiopulmonary resuscitation
      was performed within 5 min after cardiac arrest in 63 patients (96.9%).
      Defibrillation was performed 3.2 times per patient, chest compression in 52
      patients (80.0%) and tracheal intubation in 21 patients (32.3%). The restoration
      time of spontaneous circulation were achieved within 10 min in 36 cases (55.4%),
      between 11 - 30 min in 19 cases (29.2%)and between 31 - 107 min in 10 cases
      (15.4%). Thrombolysis agents (urokinase, recombinant streptokinase or recombinant
      tissue-type plasminogen activator) were given intravenously at 172 +/- 92 min
      after acute myocardial infarction. Mild hemorrhage was seen in 12 cases (18.5%)
      and there was no report on severe hemorrhage event. The hemorrhage incidence
      tended to be higher than that of reported large Chinese thrombolysis trials
      (11.1% - 15.1%, P > 0.05). CONCLUSION: Thrombolytic therapy was relatively safe
      and effective for those middle-aged male AMI patients received rapid
      cardiopulmonary resuscitation (< 5 min after cardiac arrest) and with shorter
      spontaneous circulation restoration time (<30 min).

PMID- 19100069
TI  - [Ischemic myocardial viability assessment with interleaved T1-T2* magnetic
      resonance imaging].
AB  - OBJECTIVE: To investigate the value of ischemic myocardial viability assessment
      using interleaved T1-T2* magnetic resonance imaging. METHODS: The left anterior
      descending coronary arteries (LAD) were occluded for 2 hours, followed by 1-hour
      reperfusion in 7 pigs. The hearts were then removed and perfused with a mixture
      of pig blood and crystalloid solution in 1:1 ratio. T1 relaxation times of the
      myocardium were measured with a TurboFLASH inversion-recovery sequence. The
      contrast agent, Gadolinium diethylenetriamine pentaacetic acid (Gd-DTPA) was then
      injected as a bolus into the aortic perfusion line (0.05 mmol/kg body wt). The
      first pass of the contrast agent through the heart was followed using the
      interleaved T1-T2* imaging sequence. Once the concentration of Gd-DTPA was in an
      equilibrium state, T1 relaxation times were measured again. RESULTS: The
      percentage recovery of T2* intensity (PRT2*) at the maximum T1 intensity measured
      during the first pass of the contrast agent with the interleaved T1-T2* imaging
      was statistically different in normal myocardium (37 +/- 11)%, infarct rim (90 +/
      15)% and infarct core (100 +/- 5)%, F = 66.585, P = 0.000. Moreover, the
      infarcted regions shown on PR(T2)* maps matched well with the infarcted
      myocardium measured by TTC staining. The median of T(1) relaxation time in normal
      region, infarct rim and infarct core was 531 ms, 541 ms and 1298 ms, respectively
      (H = 6.284, P = 0.043). However, normal region could not be differentiated from
      infarct rim with T1 relaxation times (q = 0.082, P = 0.775). CONCLUSION:
      Infarcted myocardium and ischemic myocardial viability can be correctly
      identified and evaluated by the interleaved T1-T2* magnetic resonance imaging in
      this model.

PMID- 19100070
TI  - [Hypotensive effects of hydrogen sulfide via attenuating vascular inflammation in
      spontaneously hypertensive rats].
AB  - OBJECTIVE: To investigate the effects of hydrogen sulfide (H2S) on vascular
      inflammation and blood pressure in spontaneously hypertensive rats (SHR).
      METHODS: Four weeks old male SHR rats were treated with saline (control, n = 7),
      sodium hydrosulfide (NaHS, a H2S donor, n = 7) and propargylglycine (PPG,
      endogenous H2S production inhibitor, n = 6) for 5 weeks. Age-natched male Wistar
      Kyoto (WKY) rats served as normotensive controls (n = 8). Five weeks later,
      systolic blood pressure (SBP) was measured in conscious and quiet rats by means
      of the standard tail-cuff method. The protein expressions of intercellular
      adhesive molecule-1 (ICAM-1), nuclear transcriptional factor-kappaB p65 (NF
      kappaB p65) and inhibitor of nuclear transcriptional factor-kappaB (IkappaB
      alpha) in thoracic aorta of rats were detected by immunohistochemical assay,
      while the expression of ICAM-1 mRNA in thoracic aorta of rats were investigated
      by in situ hybridization. RESULTS: SBP of control SHR rats was significantly
      higher than that of WKY rats (P < 0.05) accompanied by significantly upregulated
      expressions of ICAM-1 mRNA, ICAM-1 protein, NF-kappaB p65 protein in aortic
      endothelial cells (all P < 0.01), while the expression of IkappaB-alpha protein
      in aortic endothelial cells in SHR control group was significantly lower than
      that of WKY control group (P < 0.01). NaHS treated SHR rats showed significantly
      reduced SBP and downregulated expressions of ICAM-1 mRNA, ICAM-1, NF-kappaB p65
      in aortic endothelial cells and upregulated expression of IkappaB-alpha protein
      in aortic endothelial cells compared to untreated control SHR rats (all P <
      0.05). In SHR rats treated with PPG, the expressions of ICAM-1 mRNA, ICAM-1
      protein, NF-kappaB p65 protein in aortic endothelial cells were further increased
      while the expression of IkappaB-alpha protein further decreased compared with
      control SHR rats (all P < 0.05). CONCLUSION: H2S might attenuate the development
      of hypertension through by attenuating vascular inflammation reactions.

PMID- 19100071
TI  - [Effect of bone mesenchymal stem cells transplantation on malignant ventricular
      arrhythmia induced byelectrophysiological stimulation in a mini-swine model of
      acute myocardial infarction].
AB  - OBJECTIVE: To investigate the effects of autologous bone mesenchymal stem cells
      (MSC) transplantation on malignant arrhythmia induced by electrophysiological
      (EP) stimulation and cardiomyocyte ion channels remodeling in a mini-swine model
      of acute myocardial infarction (AMI). METHODS: Immediately after AMI (LAD
      occluded for 120 min), MSC (10 x 10(7), labeled by colloidal gold and co
      cultivated with 5-azacytidine, 5-aza, n = 12) or equal volume saline (n = 10)
      were injected through over-the-wire (OTW) balloon in LAD at distal over D(1). EP
      stimulation is performed after 2 hours and 4 weeks in both groups to induce
      arrhythmia. The variance of heterogeneity of sodium currents (I(Na)) and I(Na)
      steady-state inactivation curves in different zones of infracted wall were
      investigated by patch clamp technology and the relationship between ionic channel
      and ventricular arrhythmia is analyzed. RESULTS: EP induced malignant ventricular
      arrhythmia (VT) rate was similar (MSC 75% vs. saline 90%, P = 0.455) at 2 hours
      post AMI and was significantly lower in MSC group (25% vs. 80%, P = 0.012) at 4
      weeks post AMI. The Peak I(Na) current densities of the Endo, Media and Epi were
      significantly lower in MSC group [(-14.04 +/- 3.82) pA/pF, (-29.26 +/- 5.70)
      pA/pF, (-12.43 +/- 3.04) pA/pF] compared those in saline group [(-9.71 +/- 3.38)
      pA/pF, (-18.98 +/- 4.05) pA/pF, (-8.47 +/- 3.34) pA/pF, all P < 0.05]. The I(Na)
      steady-state inactivation curves of the Epi, Endo and Media in mini-swine with VT
      in MSC group [(-126.2 +/- 10.9) mV, (-106.7 +/- 11.9) mV, (-105.4 +/- 11.0) mV]
      were similar as those in saline group with VT [(-129.1 +/- 10.9) mV, (-112.2 +/-
      9.9) mV, (-109.7 +/- 9.2) mV, all P > 0.05] while significantly lower compared to
      MSC group without VT [(-93.1 +/- 13.8) mV, (-95.2 +/- 15.5) mV, (-103.4 +/- 8.7)
      mV, all P < 0.05]. The multiple logistic regression analysis showed that I(Na)
      current density (RR = 1.449, 95% CI 1.276 - 2.079, P = 0.029) and I(Na) steady
      state inactivation curves (RR = 1.092, 95% CI 1.008 - 1.917, P = 0.012) were the
      independent factors for reduced VT. CONCLUSIONS: Autologous MSC attenuated
      malignant ventricular arrhythmia induced by EP at 4 weeks in mini-swine with AMI
      which might due to altered cardiomyocyte ion channels remodeling induced by MSC.

PMID- 19100072
TI  - [Endothelin-1 overexpression inhibits rat pulmonary arterial microvascular smooth
      muscle cell apoptosis via Akt/PKB pathway].
AB  - OBJECTIVE: To investigate the effects of endothelin-1 (ET-1) overexpression on
      apoptosis of the rat pulmonary arterial microvascular smooth muscle cells (RPMC)
      in vitro. METHODS: Primary RPMC obtained from the pulmonary artery and lung
      microvasculature were identified by immunofluorescence staining and electron
      microscope technique. The RPMC was transient transfected with the pMEXneo-ET1 and
      pCDNA5-FRT-TO-ET1-3'UTR plasmids as well as the empty vector respectively via
      lipofectamine. Flow cytometry was used to assess the cell cycle and apoptosis of
      RPMC. Akt and Caspase-3 expressions were detected by Western blot and real time
      RT-PCR. RESULTS: The mRNA of ET(A) expression was significantly higher than that
      of ET(B) receptor in primary RPMC. Flow cytometry analysis revealed significantly
      reduced apoptosis in ET-1 transfected RPMC compared to that in vehicle
      transfected RPMC. Overexpression of ET-1 in RPMC also significantly increased the
      phosphorylation of Akt and reduced the cleaved Caspase-3 expression. CONCLUSIONS:
      Overexpression of the ET-1 inhibited RPMC apoptosis and activated Akt/PKB-Caspase
      3 signaling pathway, which might be responsible for ET-1 induced the pulmonary
      microvascular arteries remodeling.

PMID- 19100074
TI  - [Transcatheter retrieval detached Amplatzer atrial septal defect occluder by
      double capture device (no abstract)].

PMID- 19100073
TI  - [Effects of chronic trimetazidine treatment on atrial energy metabolism in a
      canine model of chronic atrial fibrillation].
AB  - OBJECTIVE: Aim of the present study was to investigate the effect of chronic
      trimetazidine treatment on atrial energy metabolism and endothelial function in a
      canine model of chronic atrial fibrillation (AF). METHODS: Eighteen canines were
      randomly divided into sham-operated group (n = 6), atrial pacing group (n = 6),
      and trimetazidine group (n = 6). In atrial pacing group and trimetazidine group,
      dogs were atrial paced at 400 beats per minutes for 6 weeks. Trimetazidine at 5
      mgxkg(-1)xd(-1) was given one day before rapid atrial pacing for 6 weeks.
      Creatine phosphate (CrP), adenosine triphosphate (ATP), adenosine diphosphate
      (ADP) and adenosine monophosphate (AMP) in atrial tissue were analyzed by high
      performance liquid chromatography. Total adenosine (TAN) was calculated. The
      expression of endothelial nitric oxide synthase (eNOS) in atrial tissue was
      determined by Western blot and immunohistochemical staining. In addition, plasma
      levels of von Willebrand factor (vWF) was quantified with enzyme-linked
      immunoadsorbent assay and NO(2)(-)/NO(3)(-) (NOx) was determined by nitrate
      reductase method. RESULTS: Atrial CrP (P < 0.01) and CrP/ATP were significantly
      decreased in paced atrium compared to atrium from sham-operated group (P < 0.05)
      while ATP, ADP, AMP and TAN remained unchanged (all P > 0.05). Plasma vWF was
      significantly increased and plasma NOx significantly decreased in paced animals
      compared to sham-operated animals. Atrial expression of eNOS was also
      significantly reduced in paced animals (P < 0.01). Trimetazidine treatment did
      not alter the contents of CrP, ATP, ADP, AMP and TAN, but significantly increased
      atrial eNOS expression (P < 0.05), decreased plasma vWF (P < 0.01) and increased
      plasma NOx concentration. CONCLUSION: Trimetazidine treatment affect chronic AF
      induced disturbance in energy metabolism but may improve endothelial function
      through a NOx depended manner.

PMID- 19100075
TI  - [Identification of a new missense mutation in a Chinese family with inherited
      long QT syndrome (no abstract)].

PMID- 19100077
TI  - [A review of the relationship between HSG gene and proliferative cardiovascular
      diseases (no abstract)].

PMID- 19100078
TI  - [The role of ACE 2 in blood pressure regulation (no abstract)].

PMID- 19100080
TI  - [Change minds, emphasize practical results on coronary vascular disease
      prevention].

PMID- 19100081
TI  - [Primary risk factors in Chinese patients with first acute myocardial
      infarction].
AB  - OBJECTIVE: To analyze the primary risk factors of patients with first ST
      elevation acute myocardial infarction (FSTEMI) in Beijing and Shenyang area
      between 2004--2005. The Attributable risk percentage (ARP) and population
      attributable risk percentage (PARP) of every risk factor were determined. METHOD:
      A total of 426 consecutive FSTEMI patients and 426 gender and age matched healthy
      controls were included in this 1:1 matched case-control study. RESULT:
      Multivariate logistic regression analysis showed that following 8 primary risk
      factors were associated with FSTEMI: heavy smoking (OR = 3.170), diabetes (OR =
      2.835), positive family history (OR = 2.243), lack of soybeans intake (OR =
      2.243), higher psychological stress (OR = 2.138), lack of fish intake (OR =
      1.740), lower education level (OR = 1.572) and recent adverse life events (< 6
      months before FSTEMI, OR = 1.515). The ARP are 71.53%, 58.33%, 54.05%, 40.81%,
      56.85%, 41.53%, 48.62%, 54.00%; the PARP are 38.79%, 10.40%, 4.69%, 33.72%,
      36.03%, 24.96%, 29.56%, 14.83%, respectively. CONCLUSION: In this patient cohort,
      the harmful risk factors responsible for the development of FSTEMI in Beijing and
      Shenyang areas during 2004--2005 are heavy smoking, higher psychological stress,
      lack of soybeans intake, lower education level, lack of fish intake, recent
      adverse life events, diabetes and positive family history.

PMID- 19100082
TI  - [Clinical manifestations of young and aged patients with coronary artery
      disease].
AB  - OBJECTIVE: To analyze clinical characteristics in young and aged patients with
      coronary artery disease (CAD). METHODS: The clinical and coronary angiographic
      data were compared between young (PCAD, male < 55 years old, n = 74, female < 65
      years old, n = 71) and aged (CAD, male > 55 years old, n = 106, female > 65 years
      old, n = 111) patients. Seventy-one patients excluded with CAD by angiography
      served as controls (non-CAD). The traditional risk factors (including age,
      smoking, blood pressure, lipid profile, blood glucose, BMI, family history),
      coronary angiographic changes were analyzed and compared among various groups.
      RESULTS: (1) Compared with CAD group, PCAD patients had significantly higher rate
      of smoking (50.3% vs. 38.0%, P < 0.05), significantly higher positive CAD family
      history rate (29.7% vs. 19.9%, P < 0.05) and significantly higher TG level [(2.13
      +/- 1.89) mmol/L vs. (1.78 +/- 1.14) mmol/L, P < 0.05], while had significantly
      fewer traditional risk factors (2.50 +/- 1.28 vs. 2.76 +/- 1.43, P < 0.05) and
      lower hypertension rate (59.3% vs. 73.3%, P < 0.05). There were significantly
      more PCAD patients with acute coronary syndrome (66.2% vs. 42.6%, P < 0.05), more
      PCAD patients had single vessel lesion (51.0% vs. 30.4%, P < 0.05), lower average
      lesion score (4.86 +/- 2.30 vs. 5.92 +/- 2.66, P < 0.05). (2) The logistic
      regression results showed that positive CAD family history (P = 0.029, OR =
      1.766, 95% CI 1.060 - 2.940) and smoking (P = 0.066, OR = 1.561, 95% CI 0.971 -
      2.510) are important independent risk factors for the development of PCAD.
      CONCLUSIONS: Smoking, positive family history and the increased TG might
      contribute to the pathogenesis of PCAD.

PMID- 19100083
TI  - [Impact of gender on in-hospital death in hospitalized patients with acute
      myocardial infarction].
AB  - OBJECTIVE: To investigate whether gender is an independent predictor of in
      hospital death in hospitalized patients with acute myocardial infarction (AMI).
      METHODS: This retrospective study compared baseline characteristics, therapeutic
      approaches and the occurrence rate of angina pectoris, reinfarction, heart
      failure and death during hospitalization between 1501 male and 635 female
      hospitalized patients with AMI. Multivariate logistic regression analysis was
      performed to identify risk factors predicting in-hospital death. RESULTS: In
      hospital death rate was significantly higher in female than male patients with
      AMI (11.7% vs. 6.3%, P < 0.01). Female patients with AMI were significantly older
      than male patients [(67.8 +/- 9.2) years vs. (61.1 +/- 11.9) years, P < 0.01] had
      a higher incidence of hypertension (52.1% vs. 41.1%, P < 0.01), diabetes mellitus
      (35.4% vs. 17.3%, P < 0.01), cardiac function > or = Killip class III (11.7% vs.
      5.1%, P < 0.01) and TC > 4.68 mmol/L (71.3% vs. 55.0%, P < 0.01). Cigarette
      smoking, however, was more common in males than in females (69.4% vs. 15.7%, P <
      0.01). Reperfusion therapy within the first 24 hours after symptom onset, beta
      blockers and statins use during hospitalization were significantly fewer in
      females compared with males (22.2% vs. 31.5%, P < 0.01; 64.6% vs. 71.2%, P =
      0.003; 43.1% vs. 48.0%, P = 0.041, respectively). An increased mortality was
      demonstrated in females during the hospitalization phase of AMI (11.7% vs. 6.3%,
      P < 0.01). The results of logistic regression demonstrated that age, diabetes
      mellitus, hypertension, Killip classification of cardiac function, administration
      of reperfusion therapy and beta receptor blockers use were significant predictors
      of in-hospital death in patients with AMI, with odds ratios being 1.06 (95% CI:
      1.04 - 1.08), 1.96 (95% CI: 1.32 - 2.90), 1.80 (95% CI: 1.25 - 2.58), 2.86 (95%
      CI: 2.35 - 3.48), 0.44 (95% CI: 0.30 - 0.66) and 0.51 (95% CI: 0.36 - 0.74),
      respectively. CONCLUSIONS: The in-hospital mortality of females is significantly
      higher than that of males in this patient cohort. Older age, higher risk factor
      rates, less reperfusion therapy and beta-blockers use contributed to the higher
      in-hospital mortality in female patients with AMI compared to males.

PMID- 19100084
TI  - [Case report of acute severe thrombocytopenia induced by tirofiban].

PMID- 19100085
TI  - [Impact of admission heart rate on in-hospital mortality in patients with acute
      myocardial infarction].
AB  - OBJECTIVE: To evaluate the impact of admission heart rate (HR) on in-hospital
      mortality in patients with acute myocardial infarction. METHOD: The data of 904
      in-hospital patients with ST-elevation myocardial infarction were collected from
      database of Beijing Anzhen Hospital during 2003--2004. The patients were divided
      into three groups according to the admission HR: < 80 beats/min, 80 - 90
      beats/min and > 90 beats/min. Left ventricular ejection fraction (LVEF), left
      ventricular end diastolic dimension (LVEDD), left ventricular end systolic
      dimension (LVESD) and the cases of in-hospital death were analyzed. RESULT: (1)
      Age, gender, smoking, hypertension, diabetes, the number of diseased vessel
      detected by coronary angiography were similar among three groups. LVEDD in group
      > 90 beats/min [(51.9 +/- 7.5) mm] and group 80 - 90 beats/min [(51.6 +/- 5.8)
      mm] were significantly larger compared with group < 80 beats/min [(50.3 +/- 5.3)
      mm, all P < 0.05]; LVESD in group > 90 beats/min [(39.5 +/- 8.7) mm] were also
      significantly increased compared with group 80 - 90 beats/min [(37.1 +/- 7.1) mm]
      and group < 80 beats/min [(34.8 +/- 6.2) mm, all P < 0.05]; LVEF was
      significantly lower in group > 90 beats/min (46.0% +/- 10.6%) compared with group
      80 - 90 beats/min (49.5% +/- 11.3%) and group < 80 beats/min (54.6% +/- 10.8%,
      all P < 0.05). In-hospital mortality was significantly higher in group > 90
      beats/min (18.2%) than those in group 80 - 90 beats/min and in group < 80
      beats/min (8.5%, 3.9%, all P < 0.05). (2) Multivariate analysis showed that
      admission HR was an independent risk factor for in-hospital mortality (OR =
      1.025, 95% CI 1.008 - 1.043, P = 0.005). CONCLUSION: The high level of admission
      HR was a powerful predictor of in-hospital mortality and ventricular remodeling
      in patients with acute myocardial infarction.

PMID- 19100086
TI  - [Intensive atorvastatin therapy in patients with acute myocardial infarction].
AB  - OBJECTIVE: To assess the safety and efficacy of 40 mg daily atorvastatin in
      patients with acute myocardial infarction. METHODS: A total of 1102 patients with
      AMI admitted to our hospital from 2003 to 2007 were assigned to atorvastatin 40
      mg daily within 24 hours of hospitalization and continued till 3 months post
      discharge. Patients with LDL-C < 2.0 mmol/L or increased liver enzyme level (3
      times higher than normal) at discharge received atorvastatin 20 mg daily. Lipid
      profiles, high-sensitivity C-reactive protein, liver enzyme level were measured
      at admission, hospital discharge and 3 months after discharge. RESULTS: (1)The
      mean hospitalization duration was (10.17 +/- 1.83) days. LDL-C was continuously
      decreased [(3.24 +/- 1.04) mmol/L at admission, (2.27 +/- 2.00) mmol/L at
      discharge and (1.48 +/- 0.78) mmol/L at 3 months after discharge, all P < 0.05].
      HDL-C decreased from (1.45 +/- 0.38) mmol/L to (1.20 +/- 0.30) mmol/L at hospital
      discharge, then increased to (1.65 +/- 1.79) mmol/L at 3 months after hospital
      discharge (all P < 0.05). TC and apoB were also significantly decreased from
      admission to discharge (all P < 0.05). (2) high-sensitivity C-reactive protein
      level significantly decreased from admission to hospital discharge and at 1
      months after hospital discharge [(49.71 +/- 50.46) mg/L vs. (8.80 +/- 17.66) mg/L
      vs. (2.61 +/- 2.30) mg/L, all P < 0.05]. (3) Increased ALT > 120 U/L (3 times
      higher than normal) were found in 127(11.25%), AST > 120 U/L were found in
      26(2.40%) patients at discharge. There were still 4 patients with increased ALT
      (> 120 U/L) at 1 months after discharge and all returned to normal at 3 months
      after discharge. CONCLUSION: Intensive atorvastatin therapy with a dose of 40 mg
      daily is safe and effective for patients with AMI.

PMID- 19100087
TI  - [Upregulated voltage-gated potassium channel Kv1.3 on the CD4+CD28null T
      lymphocyte from patients with acute coronary syndrome].
AB  - OBJECTIVE: The purpose of our study is to observe the voltage-gated potassium
      channel Kv1.3 expression on CD4+CD28null T cells from the peripheral blood of ACS
      patients by the patch clamp technique. METHODS: Kv1.3 potassium channels
      expression from 17 patients with ACS and 11 healthy age-matched normal controls
      was detected in single cell (CD4+CD28null T cells and CD4+CD28+ T cells) by
      fluorescence microscopy and patch clamp. RESULTS: The percent of CD4+CD28nullT
      cells are higher in the ACS (6.97% +/- 2.05%) than that in the controls (1.38% +/
      0.84%, P < 0.05). The concentration of hsCRP is directly correlated with the
      number of the CD4+CD28null T cells in the ACS (r = 0.52, P < 0.05). The
      conductance [(6.89 +/- 1.17) nS vs. (3.36 +/- 0.66) nS], dens [(1.95 +/- 0.80)
      n/microm2 vs. (1.13 +/- 0.57) n/microm2] and numbers [(574.5 +/- 97.6) n/cell vs.
      (280.3 +/- 55.3) n/cell] of the Kv1.3 channels on the CD4+CD28null T cells are
      significantly higher than those on the CD4+CD28+ T cells (all P < 0.01) in ACS
      patients, but were similar on CD4+CD28+ T cells between ACS patients and
      controls. CONCLUSION: The CD4+CD28null T cells in the ACS and the numbers of
      Kv1.3 channels on the CD4+CD28null T cells from the ACS patients are
      significantly upregulated and might contribute to the pathogenesis of ACS.

PMID- 19100088
TI  - [Interventional therapy for structural heart diseases in People's Liberation Army
      hospitals between 2005 and 2006].
AB  - OBJECTIVE: To evaluate the efficacy and safety of interventional therapy in
      structural heart diseases in 38 PLA hospitals. METHODS: Data including patient
      number underwent interventional therapy for structural heart disease, procedure
      details, immediate procedural complications were retrospectively collected in all
      the military hospitals between January 2005 and December 2006. RESULTS:
      Successful interventional therapy was achieved in 8692 out of 8862 patients
      (98.08%) with structural heart disease. Transcatheter closure of ventricular
      septal defect (VSD), atrial septal defect (ASD) and patent ductus arteriosus
      (PDA), and percutaneous balloon dilatation of mitral valve stenosis (MS) and
      pulmonary valve stenosis (PS) were the most performed procedures (97.99%). Up to
      91.23% patients underwent transcatheter closure with domestic devices. The
      incidence of procedure-related complications was 4.33% (n = 384) which were most
      frequently associated with VSD closure. The commonest procedural complications
      included conduction blockades (n = 260), residue shunt (n = 42), device
      detachment (n = 30) and tricuspid incompetence (n = 22). Although the procedures
      performed in 2005 and 2006 increased 57.32% compared with those in 2003 and 2004,
      the success rate and the incidence of complications remained unchanged.
      CONCLUSION: Percutaneous treatment of structural heart disease is a safe and
      feasible alternative to surgery. Simulate complications arise long after the
      treatment, which suggests the importance of long-term follow-up for those
      patients who hare undergone interventional therapy.

PMID- 19100089
TI  - [Clinical features of unexpected sudden death clustered in 7 families in Yunnan
      Province].
AB  - OBJECTIVE: To investigate the clinical features of unexpected sudden death (SUD)
      clustered in families in Yunnan province. METHODS: This retrospective study
      analyzed the clinical features of SUD occurred between July to September 2005 in
      7 families in Yunnan province. RESULTS: All 16 SUD patients shared common
      clinical features such as fatigue and repeated syncope and one group of SUD
      patients (n = 8 from 4 families) presented with the gastric intestinal tract
      manifestations including nausea, vomiting, abdominal pain and diarrhea with
      suspected dietary history and abnormal laboratory enzyme findings (GOT/GPT,
      CK/CKMB, LDH/LDH1 etc.). In SUD patients without gastric intestinal tract
      manifestations (n = 8 from 3 families), there were no clear symptoms before death
      and repeated ventricular tachycardia and ventricular fibrillation were recorded
      in one survivor. There was no clear evidence for the involvements of hereditary
      and infectious factors for observed SUD. CONCLUSION: The reason for the
      unexpected sudden death clustered in 7 families in Yunnan remains unclear.
      Repeated syncope and fatigue served as the common clinical features in the
      presence or absence of gastric intestinal tract manifestations in all SUD cases.
      Further studies are needed to clarify the pathology and detailed clinical
      manifestations of SUD occurred in this area.

PMID- 19100090
TI  - [Heparin-induced thrombocytopenia after percutaneous balloon mitral
      valvuloplasty].

PMID- 19100091
TI  - [Association between metabolic syndrome and chronic kidney disease].
AB  - OBJECTIVE: To explore the associations between the metabolic syndrome (MS) and
      chronic kidney disease (CKD) in patients admitted to our department. METHODS: A
      total of 525 consecutive patients were included in this cross-sectional study.
      Body height, weight, waist circumference, biochemical and serum lipid profile
      were measured. An oral glucose tolerance test (OGTT) was performed in patients
      without diabetes. CKD was defined by creatinine-based estimates of glomerular
      filtration rate (eGFR). The MS was defined according to IDF (International
      Diabetes Federation) definition. RESULTS: (1) Serum creatinine (Cr) was
      significantly increased and the mean level of eGFR was significantly reduced in
      patients with MS compared to those without MS [Cr (93.81 +/- 31.06) micromol/L
      vs. (108.65 +/- 36.05) micromol/L, P < 0.001; eGFR (61.14 +/- 17.40) ml.min(
      1).1.73 m(-2) vs. (73.64 +/- 17.03) ml.min(-1).1.73 m(-2), P < 0.001]. (2) eGFR
      decreased in proportion to increasing number of the MS components and was the
      lowest when patients had 5 components of the MS (P < 0.001). (3) Compared to
      patients without MS, the multivariate-adjusted (adjustment for age, sex, chronic
      heart failure and the use of ACEI or ARB medication) odds ration (95% CI) of CKD
      was 4.34 (95% CI: 2.77 - 6.81) in patients with MS. Compared to patients without
      any components or only with one component, the multivariate-adjusted odds ratios
      (95% CI) of CKD were 3.12 (1.41 - 6.89), 8.21 (3.78 - 17.82) and 14.72 (6.14 -
      35.30) for those with 3, 4 and 5 components, respectively. In the multivariate
      models, elevated blood pressure, hyperglycemia, abdominal obesity and elevated
      triglycerides were significantly associated with an increased odds ratio (95% CI)
      of CKD, 1.75 (1.04 - 2.92), 1.98 (1.26 - 3.11), 2.42 (1.41 - 4.16) and 2.65 (1.68
      - 4.19), respectively. CONCLUSION: There are positive associations between MS,
      its components and CKD. The risk of CKD increased in proportion to increased
      number of MS components. Elevated blood pressure, hyperglycemia, abdominal
      obesity and hypertriglyceridemia also increase the risk of CKD.

PMID- 19100092
TI  - [Effects of antiarrhythmic drug use on atrial fibrillation recurrence in atrial
      fibrillation patients post circumferential pulmonary vein ablation].
AB  - OBJECTIVE: This prospective and randomize-controlled trial was designed to
      investigate the effects of antiarrhythmic drug use (AADs) on atrial fibrillation
      (AF) recurrence in atrial fibrillation patients post circumferential pulmonary
      vein ablation (CAPV). METHODS: Seventy-four consecutive AF patients underwent
      CAPV (41 paroxysmal and 33 drug refractory AF) were randomly assigned to receive
      placebo (Group A) or AADs (Group B) for 3 months. Monthly standard
      electrocardiograms (ECG) and Holter monitoring were performed to assess AF
      recurrences during 17 - 28 months follow-up. RESULTS: CAPV was successful in all
      patients. The recurrence rate of AF in Group B was significantly lower than that
      in Group A at 3 months post CAPV (13.5% vs. 37.8%, P < 0.01) and similar
      thereafter (29.7% vs. 24.3% at 12 months and 8.1% vs. 8.1% at more than 12
      months, all P > 0.05). There was also no significant difference in terms of total
      recurrence rate between the two groups (37.8% vs. 32.4%, P > 0.05). CONCLUSION:
      Post CAPV antiarrhythmic drug therapy could only decrease the early AF recurrence
      rate but was not effective for decreasing AF recurrence rate on later stage.

PMID- 19100094
TI  - [Role of renin-angiotensin system, PPARalpha, PPARgamma in the development of
      alcoholic cardiomyopathy].
AB  - OBJECTIVE: To explore the time course of renin-angiotensin system (RAS),
      peroxisome proliferator-activated receptor (PPAR) alpha and PPARgamma change in
      an animal model of alcoholic cardiomyopathy (ACM). METHODS: Adult rats were
      divided into three groups: ACM group (A, 10% alcohol as drinking water plus 5 ml
      60% alcohol.kg(-1).d(-1) per gavage in the 1st week; 10% alcohol as drinking
      water plus 10 ml 60% alcohol/kg bid per gavage in the 2nd week, 20% alcohol as
      drinking water plus 15 ml 60% alcohol/kg bid per gavage during week 3 to week
      16), ACM/ARB group(B, A + Irbesartan 5 mg.kg(-1).d(-1) per gavage) and control
      group (C). mRNA expressions and activities of renin, angiotensin, ACE and AT1
      were detected with RT-PCR and radioimmunoassay methods. Protein expressions of
      PPARalpha and PPARgamma were determined with Western blot. Echocardiogram, optic
      (HE) and electron microscope examinations were also performed. Parameters were
      obtained at 2 or 6 months (n = 7 - 10 each). RESULTS: Compared with group C,
      LV/BW ratio was significantly increased and LVEF significantly decreased,
      activities and expressions of Ang I, Ang II and renin were gradually increased,
      protein expressions of PPARalpha were gradually decreased at 2 and 6 months in
      group A (all P < 0.05). These changes could be partly attenuated by Irbesartan.
      CONCLUSION: Activated RAS and decreased protein expressions of PPARalpha and
      PPARgamma contributed to the development of ACM.

PMID- 19100095
TI  - [Erythropoietin suppresses the expressions of TGF-beta1 and collagen in rat
      cardiac fibroblasts induced by angiotensin II].
AB  - OBJECTIVE: Recent studies have shown cardiac protection effects of erythropoietin
      (EPO). The present experiment was designed to investigate the effects of EPO on
      TGF-beta1, nitric oxide synthase (NOS), collagen contents induced by angiotensin
      II (Ang II) in rat cardiac fibroblasts (CFs) and explore the roles of PI3-K/Akt
      signaling pathway on related effects. METHODS: Neonatal rat CFs was isolated by
      collagenase and trypsinase digestion methods. PBS, EPO, Ang II in the absence or
      presence of LY294002, an inhibitor of PI3-K, or L-NAME, an inhibitor of NOS, were
      added to CFs and cultured for 24 hours. The concentration of collagen I and
      collagen III in culture medium were quantitated by ELISA. The levels of nitric
      oxide (NO) and the activities of NOS as well as NOS isoforms were measured by
      chemical enzymic method. Western blot was applied to detecting the protein
      expressions of Akt, p-Akt, eNOS, iNOS, and TGF-beta1. RESULTS: The concentrations
      of collagen I and collagen III in CFs culture medium were significantly increased
      while the level of NO was significantly decreased by Ang II and these changes
      were significantly suppressed by EPO in a dose dependent manner. The effects of
      EPO on eNOS and NO could be blocked by LY294002. L-NAME could block EPO's effect
      on NO but not on the eNOS expression. The suppression effects on expressions of
      TGF-beta1 and collagen by Ang II in CFs were blocked by both LY294002 and L-NAME.
      CONCLUSION: EPO suppresses the upregulated expressions of TGF-beta1 and increased
      production of collagen induced by Ang II through activating the PI3-K/Akt
      signaling pathway in neonatal rat CFs.

PMID- 19100096
TI  - [Increased expression of transient receptor potential melastatin 7 in mouse
      cardiac fibroblasts post myocardial infarction].
AB  - OBJECTIVE: To observe transient receptor potential melastatin 7-like (TRPM7L)
      expression changes post myocardial infarction (MI) in mouse cardiac fibroblast
      (CF). METHODS: TRPM7 expression and Ca2+ influx in CF from MI and control mice
      were quantified by mRNA RT-PCR and whole cell patch clamp technique. RESULTS: (1)
      TRPM7 expression was significantly upregulated post MI and Ca2+ influx of CF were
      significantly increased post MI [(7.4 +/- 0.7) pA/pF vs. (16.2 +/- 1.7) pA/pF, P
      < 0.01] and Ca2+ influx of CF increased 3-fold under lower pH condition; (2)
      These effects could be blocked by knock-out TRPM7 gene with SiRNA. CONCLUSION:
      TRPM7L upregulation post MI and under lower pH condition are responsible for
      increased Ca2+ influx in CF.

PMID- 19100097
TI  - [Upregulated PGC-NRF-mtTFA expressions contributed to the development of
      atherosclerosis in rabbits fed with a high fat diet].
AB  - OBJECTIVE: To investigate the relationship between PPAR coactivator 1 (PGC-1),
      nuclear respiratory factor (NRF), mitochondrial transcription factor A (mtTFA)
      expressions of vascular smooth muscle cells (VSMC) and development of
      atherosclerosis in a rabbit model. METHODS: Atherosclerotic model was established
      by feeding the rabbits with high-fat diet for 4, 8 and 12 weeks (n = 10 each).
      Another 8 rabbits fed with normal diet served as normal controls. Intima-media
      ratio, mRNA and protein expressions of PGC-1, NRF, mtTFA and SMemb, a marker for
      synthetic VSMC, were detected on aorta specimens. RESULTS: With the blood lipid
      increased, the intima-media ratio rose from (0.031 +/- 0.010) microm up to (0.814
      +/- 0.258) microm during 12 weeks. Increasing SMemb means that synthetic VSMC
      grew more and more. The expressions of PGC-1 became significant after 4 weeks (P
      < 0.01), while that of NRF-1 and mtTFA rose significantly after 8 weeks (P <
      0.01). CONCLUSIONS: The PGC-NRF-mtTFA pathway might play a critical role in VSMC
      proliferation and development of atherosclerosis.

PMID- 19100098
TI  - [Human bone marrow mesenchymal stem cells cocultured with semi-permeable membrane
      separated neonatal rat ventricular myocytes differentiated into cardiomyocyte
      phenotype].
AB  - OBJECTIVE: To investigate the ability of human bone marrow mesenchymal stem cells
      (hBMSCs), cocultured with semi-permeable membrane separated neonatal rat
      ventricular myocytes, to differentiate into cardiomyocytes. METHODS: hBMSCs were
      isolated and purified by density gradient centrifugation and adherence screening
      method. Cells were expanded as undifferentiated cells in culture for more than 3
      passages and their phenotypes were identified with flow cytometer. hBMSCs were
      cocultured with neonatal rat ventricular myocytes in a rate of 1:10 separated by
      semi-permeable membrane. GATA4 mRNA was detected by RT-PCR; Immunocytochemistry,
      and Immunostaining were used to detect sarcomeric alpha-actinin, desmin, cTnT,
      and cTnI protein level. RESULTS: CD29 (98.64% +/- 0.80%) and CD44 (96.70% +/-
      1.50%) were the major surface markers of hBMSCs. After coculturing with semi
      permeable membrane separated neonatal rat ventricular myocytes, the first
      contraction of single cells was noted at day 7 and GATA4 expression was detected
      on these cells by RT-PCR after 1 to 3 weeks coculture. Desmin, sarcomeric alpha
      actinin, cTnI and cTnT could be detected by immunocytochemistry and
      immunostaining on some of these cells. CONCLUSION: hBMSCs possess the potential
      to differentiate into myocardial cell phenotype in the cardiac microenvironment.
      Direct contact with cardiomyocytes was not necessary required for hBMSCs
      differentiation.

PMID- 19100099
TI  - [Predictive value of combined measurements of body mass index and waist
      circumference for the risk of cardiovascular disease].
AB  - OBJECTIVE: To evaluate the predictive value of the combined measurements of body
      mass index (BMI) and waist circumference (WC) for the risk of cardiometabolic
      diseases (including diabetes, hypertension, and dyslipidemia) and ischemic
      cardiovascular disease. METHOD: A total of 30,378 Chinese people from 11
      provinces were studied in this prospective study conducted from 1992 to 2003.
      Multivariable logistic and Cox regression were used respectively to determine the
      predictive value of WC for cardiometabolic diseases and ischemic cardiovascular
      disease within each BMI categories. RESULTS: (1) The prevalence of obesity were
      10% defined by BMI. Among them, 76.4% had abdominal obesity defined by WC. The
      prevalence of abdominal obesity was 17.5% by WC categories, and 43.4% of them
      were classified as obesity by BMI. (2) The prevalence rates of cardiometabolic
      diseases were higher in individuals with elevated WC within each BMI category.
      (3) Compared with subjects with normal BMI and WC, the risk of ischemic
      cardiovascular disease increased by 38% (RR = 1.383, 95% CI 1.083 - 1.765) in
      overweight subjects with elevated WC and by 57% (RR = 1.570, 95% CI 1.226 -
      2.010) in obese subjects with elevated WC. CONCLUSION: Combined measurements of
      BMI and WC provide a better prediction for the risk of cardiometabolic diseases
      and ischemic cardiovascular disease.

PMID- 19100100
TI  - [Case report of one patient with idiopathic ventricular tachycardia and Narrow
      QRS complex].

PMID- 19100101
TI  - [Perspective of microRNA in cardiovascular-associated diseases].

PMID- 19100102
TI  - [Progress in genes causing idiopathic dilated cardiomyopathy].

PMID- 19100104
TI  - [Cell therapy for coronary heart diseases: fact or fancy].

PMID- 19100105
TI  - [Inflammatory high density lipoprotein: structure or function changes and
      association clinical implications].

PMID- 19100106
TI  - [Systematic review on safety of intracoronary autologous bone marrow stem cells
      transfer in patients with acute myocardial infarction].
AB  - OBJECTIVE: To estimate the safety of intracoronary autologous bone marrow stem
      cells (BMSC) transfer in patients with acute myocardial infarction. METHODS: A
      systematic literature search of PubMed, MEDLINE, Cochrane EBM, BIOSIS, EMBASE and
      Chinese Journal Full-text Database between January 1990 and May 2007, was
      performed. Inclusion criteria required that patients received intracoronary BMSC
      transfer after coronary reperfusion therapy for primary acute myocardial
      infarction; study design involved patient randomization and matching placebo
      group as well as detailed safety data with more than 3 months follow-up results.
      RESULTS: A total of 5 trials with 620 patients were available for analysis. The
      pooled statistics showed similar results between BMSC and placebo groups in terms
      of occurrence of the individual clinical adverse events and the combined endpoint
      death, recurrence of myocardial infarction, or revascularization procedures. The
      combined endpoint death, recurrence of myocardial infarction, revascularization
      procedures, or rehospitalization for heart failure was significantly reduced in
      the BMSC group compared with the control group at more than one year follow-up
      (OR = 0.45, 95%CI 0.28 - 0.74, P = 0.002). Likewise, the occurrence of
      revascularization and the combined endpoint death, recurrence of myocardial
      infarction, or revascularization procedures were significantly reduced when BMSC
      transplantation was performed between 4 and 7 days after primary percutaneous
      coronary intervention (PCI) (OR = 0.60, 95%CI 0.37 - 0.97, P = 0.04; OR = 0.58,
      95%CI 0.37 - 0.91, P = 0.02, respectively). In contrast, there was a significant
      increase in the combined endpoint revascularization and recurrence of myocardial
      infarction when BMSC transplantation was performed within 24 hours after PCI (OR
      = 2.56, 95%CI 1.03 - 6.34, P = 0.04). CONCLUSIONS: Post PCI intracoronary
      autologous BMSC transplantation in patients with acute myocardial infarction is
      safe, especially in patients received BMSC transplantation between 4 and 7 days
      after primary PCI than patients received BMSC transplantation within 24 hours
      post PCI.

PMID- 19100107
TI  - [Lovastatin protects mesenchymal stem cells against hypoxia and serum deprivation
      induced apoptosis through activation of PI3K/Akt and ERK1/2 signaling pathways].
AB  - OBJECTIVE: To investigated the effect of lovastatin on hypoxia and serum
      deprivation (Hypoxia/SD) induced rat MSCs apoptosis in vitro and associated
      signaling pathway changes. METHODS: MSCs were isolated from Sprague-Dawley rats.
      The anti-apoptotic effects of lovastatin were detected using Hoechst33342 and
      annexin V-FITC/PI binding assay by Flow cytometric analysis. The phosphorylation
      of Akt and ERK1/2, the cytochrome C and the cleaved caspase-3 were detected by
      Western blot. RESULTS: Lovastatin (0.01 - 1 micromol/L) significantly reduced
      Hypoxia/SD-induced MSCs apoptosis and increased Akt phosphorylation, reduced
      caspase-3 activation and cytochrome c release from mitochondria to cytosol in a
      time dependent manner. These effects could be significantly blocked by both PI3K
      inhibitor, LY294002 and ERK1/2 inhibitor, U0126. CONCLUSIONS: Our results showed
      that lovastatin protects MSCs from Hypoxia/SD-induced apoptosis via activating
      PI3K/Akt and ERK1/2 signaling pathways suggesting a potential role of statins as
      an adjunct therapeutic agent during transplanting MSCs into damaged heart after
      myocardial infarction.

PMID- 19100108
TI  - [Generation of a P19-alphaMHC-EGFP reporter line and cardiomyocyte
      differentiation].
AB  - OBJECTIVE: To generate a P19-alphaMHC-EGFP reporter line and induce cardiomyocyte
      differentiation of this reporter line. METHODS: The P19 cells were transfected
      with palphaMHC-EGFP, a P19-alphaMHC-EGFP reporter line was obtained after G418
      selection and limited dilution of recombinant clones. The reporter line was
      induced to differentiate into cardiomyocytes which would beat and express green
      fluorescent protein. A comparison of cardiomyocyte differentiation rate and cTnI
      expression amount between the reporter line and the untransfected P19 cells was
      also performed. The ultrastructure was observed under transmission electron
      microscope. RESULTS: The ultrastructure characteristics indicated cardiomyocytes
      like changes on induction day 10. The beating cardiomyocytes which express GFP
      appear in the seventh induction day. The cardiomyocyte differentiation rate and
      cTnI expression amount of P19-alphaMHC-EGFP reporter line were similar as those
      in untransfected P19 cells (P > 0.05). CONCLUSION: The P19-alphaMHC-EGFP reporter
      line is of great benefit for identifying and purifying cardiomyocytes from
      undifferentiated P19 cells without influencing the differentiation of P19 cells.
      This feature makes P19-alphaMHC-EGFP reporter line a promising cell source for
      clinical cardiomyocyte replacement therapy.

PMID- 19100109
TI  - [In vitro MR imaging of Fe2O3-arginine labeled heNOS gene modified endothelial
      progenitor cells].
AB  - OBJECTIVE: To explore the feasibility of in vitro magnetic resonance imaging on
      Fe2O3-arginine labeled heNOS gene modified endothelial progenitor cells (EPCs).
      METHODS: Fe2O3 was incubated with arginine to form Fe2O3-arginine complex. Rabbit
      peripheral blood mononuclear cells (MNCs) were isolated and EPCs were isolated by
      adherence method, expanded and modified with heNOS gene using Lipofectamine 2000.
      After 48 hours, genetically modified EPCs were incubated with Fe2O3-arginine for
      24 hours. Intracellular iron was detected by Prussian blue stain. The expression
      of heNOS gene was detected by Western blot. MTT assay was used to evaluate cell
      survival and proliferation of Fe2O3-arginine labeled heNOS-EPCs. Flow cytometry
      was used to measure cell apoptosis. The cells underwent in vitro MR imaging with
      various sequences. RESULTS: Iron-containing intracytoplasmatic vesicles could be
      clearly observed with Prussian blue staining, and the labeling rate of labeled
      heNOS-EPCs were similar to that of labeled EPCs (around 100%). Survival and
      apoptosis rates obtained by MTT and flow cytometry analysis were similar among
      labeled heNOS-EPCs, labeled EPCs and unlabeled EPCs with Fe2O3-arginine. The
      signal intensity on MRI was equally decreased in labeled heNOS-EPCs and labeled
      EPCs compared with that in unlabeled cells. The percentage change in signal
      intensity (DeltaSI) was most significant on T2*WI and DeltaSI was significantly
      lower in cells labeled for 7 days than that labeled for 1 days. CONCLUSIONS: The
      heNOS gene can be successfully transfected into rabbit peripheral blood EPCs
      using Lipofectamine2000. The heNOS-EPCs can be labeled with Fe2O3-arginine
      without significant change in viability and proliferation capacity. The labeled
      heNOS-EPCs can be imaged with standard 1.5 T MR equipment. The degree of MR
      signal intensity may indirectly reflect the cell count, growth and division
      status.

PMID- 19100110
TI  - [Efficacy comparison between drug-eluting stents versus cutting balloon
      angioplasty followed by bare metal stents for the treatment of ostial lesions of
      the left anterior descending coronary artery].
AB  - OBJECTIVE: To compare the short and long-term clinical and angiographic outcomes
      of drug-eluting stents (DES) versus cutting balloon angioplasty followed by bare
      metal stents (CBA + BMS) for the treatment of ostial lesions of the left anterior
      descending coronary artery (LAD). METHODS: A total of 51 consecutive patients
      with LAD ostial lesions were treated by DES and all patients had completed 2-year
      clinical follow-up, 50 consecutive patients with LAD ostial lesions treated by
      CBA + BMS and followed up for 2 years prior to the DES era (May 2000 to November
      2003) served as control group. RESULTS: In DES group, one patient experienced
      acute myocardial infarction (AMI) during hospitalization, the in-hospital major
      adverse cardiac event (MACE) was 1.96% (1/51), angiography follow-up data at 6-8
      months were available in 29 patients and the in-DES restenosis was 10.3% (3/29),
      at 2-year clinical follow-up, 1 patient died, 4 patients received target lesion
      revascularization. Total MACE rate was 9.8% (5/51). In CBA + BMS group, there was
      no in-hospital death and AMI. Angiographic follow-up at 6-8 months was completed
      in 28 cases and in-stent restenosis rate was 17.9% (5/28). During 2-year follow
      up, there was no death and AMI and 6 patients underwent target lesion
      revascularization. MACE rate was 12% (6/50) in this group. CONCLUSION: This study
      showed that both clinical and angiographic outcomes were comparable between DES
      and CBA + BMS treated patients with LAD ostial lesions during the 2-year follow
      up period.

PMID- 19100111
TI  - [Acute angiographic and clinical outcomes of patients with calcified chronic
      total occlusion underwent percutaneous coronary intervention].
AB  - OBJECTIVE: To evaluate the in-hospital outcome of patients with calcified chronic
      total occlusion (CTO) lesion underwent percutaneous coronary intervention (PCI).
      METHODS: The clinic and lesion characteristics as well as acute PCI outcome were
      analyzed in 726 patients with calcified CTO [624 detected by coronary angiography
      (CAG) and 102 detected by intravascular ultrasound (IVUS)] and received PCI
      therapy from June 1995 to February 2007 in our department. RESULTS: There were
      728 diseased vessels with 732 lesions in these patients. Total procedure success
      rate (80.6% vs. 89.2%, P < 0.05) and the lesion success rate (80.2% vs. 88.2%, P
      < 0.05) were significantly lower in calcified CTO detected by CAG compared to
      that detected by IVUS. The causes of procedure failures in CAG detected patients
      were as follows: 87 guide failure, 21 balloon failure, 8 procedure related
      complications and 5 low TIMI blood flow (grade 2) at the end of PCI procedure.
      The causes of procedure failures in IVUS detected patients were as follows: 7
      guide wire failure, 2 balloon failure, 1 procedure related complications and 1
      patient with low TIMI blood flow (grade 2). The in-hospital major adverse cardiac
      events (MACE) rate was 1.1% in CAG detected calcified CTO and 1.0% in IVUS
      detected calcified CTO (P > 0.05). CONCLUSION: PCI therapy resulted in
      satisfactory procedure success rate and in-hospital outcome for patients with
      calcified CTO and IVUS is helpful for further increasing the PCI procedure
      success rate in patients with calcified CTO.

PMID- 19100112
TI  - [Association between fasting plasma glucose and the 5 years outcome post PCI in
      aged patients with coronary artery disease].
AB  - OBJECTIVE: To observe the association between fasting plasma glucose (FPG) and 5
      years outcome post PCI in aged patients with coronary artery disease (CAD).
      METHODS: A total of 269 patients (mean age 63.8 +/- 9.4 years, 236 males) with
      CAD underwent PCI between January 2000 and December 2001 were followed up and
      data on angiographic restenosis, the major adverse cardiac events, the cumulative
      survival rates and the correlated risk factors were collected and analyzed.
      Patients were divided into 4 groups according to the levels of their FPG at
      baseline (group 1: FPG < 5.6 mmol/L; group 2: 5.6 mmol/L < or = FPG < 6.1 mmol/L;
      group 3: 6.1 mmol/L < or = FPG < 7.0 mmol/L; group 4: FPG > or = 7.0 mmol/L).
      RESULTS: At the end of the 5 years follow-up, the incidences of major adverse
      cardiac events, target lesion revascularization, recurring angina pectoris and
      angiographic restenosis of group 2 were significantly higher than those of group
      1 (P < 0.05) and similar as those in group 3 (P > 0.05). The cumulative survival
      rates of cardiovascular events of group 2, group 3 and group 4 were all
      significantly decreased compared with group 1 (P < 0.05). The logistic regression
      model analysis showed that FPG was an independent risk factor for angiographic
      restenosis, incidence of major adverse cardiac events, all-cause mortality and
      recurring angina pectoris (P < 0.05). CONCLUSION: FPG > or = 5.6 mmol/L and over
      is associated with increased incidences of major adverse cardiac events in aged
      patients with CAD who underwent PCI.

PMID- 19100113
TI  - [Association among circulating endothelial progenitor cells, insulin resistance
      and severity of coronary lesions in patients with coronary artery disease].
AB  - OBJECTIVE: To investigate the correlation between the number and activity of
      circulating endothelial progenitor cells (EPCs), insulin resistance and severity
      of coronary lesions in patients with coronary artery disease (CAD). METHODS:
      Patients with coronary angiography evidenced CAD were divided in insulin
      resistance group (IR, n = 25) and insulin sensitive group (IS, n = 44) according
      to insulin level, 25 health volunteers served as control. Circulating EPCs were
      marked as KDR/CD133+ cells via fluorescence-activated cell sorter analysis. EPCs
      were also isolated from peripheral blood and cultured in vitro for 7 days,
      identified by DiI-acLDL uptake and lectin staining methods. EPCs migration
      activities were determined by modified Boyden chamber assay, EPCs proliferation
      activities were determined by MTT assay. RESULT: Circulating EPCs number was
      significantly lower in IR group compared with IS group [(0.34 +/- 0.08) per
      thousand vs. (0.47 +/- 0.09) per thousand, P < 0.01] and control group (P <
      0.05). Both insulin resistance index (r = -0.291, P = 0.01)and Gensini score (r =
      -0.3984, P = 0.006)were negatively correlated with number of circulating EPCs.
      Proliferation and migration capacities of EPCs were also significantly lower in
      IR group compared to those in IS group (all P < 0.05) and control group (all P <
      0.05). CONCLUSIONS: Insulin resistance/hyperinsulinemia could aggravate severity
      of coronary artery lesions via reducing the number and activities of circulating
      EPCs in patients with CAD.

PMID- 19100114
TI  - [Reduced cardiopulmonary exercise capacity in patients with essential
      hypertension: impact of left ventricular hypertrophy].
AB  - OBJECTIVE: To evaluate the cardiopulmonary exercise capacity in patients with
      essential hypertension (EH) complicating with or without left ventricular
      hypertrophy (LVH). METHODS: Graded maximal exercise test on the bicycle ergometer
      with respiratory gas analysis were performed in 30 gender and age matched
      normotensive controls, 40 EH patients without LVH and 30 EH patients with LVH
      (LVMI>125 g/m2 in males and > 120 g/m2 in females). Metabolic equivalents (METs),
      oxygen uptake (VO2), oxygen uptake to body mass ratio (VO2/kg) and oxygen uptake
      to heart beat ratio (VO2/HR) at time of reaching anaerobic threshold (AT) and at
      maximal oxygen uptake (VO2max) were measured and compared. RESULTS: METs and
      VO2/kg were significantly reduced in EH patients with or without LVH compared
      with controls [at AT, METs: 3.57 +/- 0.8 and 4.34 +/- 1.47 vs. 5.21 +/- 1.45;
      VO2/kg: 12.38 +/- 2.85 and 14.42 +/- 4.33 vs. 18.48 +/- 4.52, all P < 0.01; at
      VO2max, METs: 4.94 +/- 1.24 and 5.90 +/- 1.51 vs. 6.96 +/- 1.85; VO(2)/kg: (17.20
      +/- 4.34) mlxmin(-1)xkg(-1) and (20.41 +/- 4.59) mlxmin(-1)xkg(-1) vs. (24.04 +/-
      5.21) mlxmin(-1)xkg(-1), all P < 0.01]. METs and VO2/kg at both time points were
      also significantly reduced in EH patients with LVH compared EH patients without
      LVH (all P < 0.05). The lower VO2/kg in hypertensive patients was significantly
      correlated to higher LVMI (P < 0.05). CONCLUSIONS: Cardiopulmonary exercise
      capacity was reduced in hypertensive patients, especially in hypertensive
      patients with LVH.

PMID- 19100115
TI  - [Relationship between microalbuminuria and cognition in primary hypertension
      patients].
AB  - OBJECTIVE: To study the relationship between microalbuminuria and cognitive
      impairment in primary hypertensive patients. METHODS: A total of 200 hypertensive
      patients were included in this study. Blood pressure, body height and weight,
      total cholesterol, triglyceride, fasting plasma glucose, 2 hour-postprandial
      blood sugar, insulin level and urine protein were measured. Microalbuminuria and
      urine creatinine were determined in patients without proteinuria. The risk
      stratification of hypertension was evaluated. The cognitive function and
      calculate scores were tested by the Mini Mental State Examination (MMSE) and
      patients were divided into two groups: > 24-scores were classified as normal
      cognition group, < or = 24-scores as impaired cognition group. RESULTS: Among the
      200 hypertensive patients, proteinuria was detected in 25 patients. There was no
      significant difference in the cognitive function between patients with and
      without proteinuria (P > 0.05). There were significant differences on age,
      educational level, occupation, smoking, history of coronary heart disease,
      history of cerebrovascular disease, the risk stratification of hypertension,
      microalbuminuria/creatinine ratio, postprandial insulin level, cholesterol and
      diastolic blood pressure between normal cognition function group and impaired
      cognition function group (all P < 0.05). Multivariate logistic regression
      analysis showed that microalbuminuria, educational level and the risk
      stratification of hypertension were significantly correlated to cognition
      impairment (all P < 0.05). CONCLUSIONS: Educational level, the risk
      stratification of hypertension and microalbuminuria are associated with cognitive
      impairment in this patient cohort.

PMID- 19100116
TI  - [Safety and efficiency of pacing at right ventricular outflow versus at
      ventricular cardiac apex].
AB  - OBJECTIVE: To compare the safety and efficiency of pacing at right ventricular
      outflow versus right ventricular apex. METHOD: Patients were divided into two
      groups: pacing at ventricular cardiac apex (common pacing group, n = 22) and
      pacing at right ventricular outflow tract (uncommon pacing group, n = 18).
      RESULTS: Impedance and amplitude of R-wave were similar during implantation
      between the two groups (all P > 0.05). The pacing threshold and electric current
      were significant higher in uncommon group than those in common pacing group (all
      P < 0.05), however, these differences disappeared at 1 month post pacemaker
      implantation (all P > 0.05). The mean QRS duration tended to be shorter in
      uncommon pacing group compared to that in common pacing group (P > 0.05). There
      was no pacemaker associated adverse effect in both groups. CONCLUSION: The safety
      and efficiency of pacing at right ventricular outflow was similar as those of
      pacing at right ventricular apex.

PMID- 19100117
TI  - [Effects and potential mechanisms of short-term use of simvastatin on myocardial
      no-reflow after ischemia-reperfusion in rats].
AB  - OBJECTIVE: The main objective of this study is to assess the the effect of
      simvastatin (sim) on myocardial no-reflow (NR) and explore the possible potential
      mechanisms. METHODS: Adult male Wistar rats were randomized into sham group (n =
      12), I/R (90 min ischemia via coronary ligation/120 min reperfusion, n = 18) and
      I/R plus sim group (20 mgxkg(-1)xd(-1) sim pretreated via gavage beginning 3 days
      before I/R, n = 18). After reperfusion, area at risk/area of left ventricular
      (RA/LVA), area of NR, determined by the area not perfused by thioflavin-S/area at
      risk (NA/RA) and area of myocardial infarction/area at risk (MIA/RA) were
      measured. Myocardium homogenate was used to determine the activity of eNOS, iNOS
      and MPO, and the content of NO and MDA. Myocardial immunohistochemistry was
      performed to determine the positive index of NF-kappaB p65 in cardiomyocytes and
      arteriole. RESULTS: The NR and myocardial infarction areas in I/R plus sim group
      were significantly smaller than those in I/R group (34.10 +/- 7.05 vs. 52.09 +/-
      6.89, 78.80 +/- 7.60 vs. 90.13 +/- 5.72, each P < 0.05) while the ischemia area
      was similar between the 2 groups (P > 0.05). The myocardial activities of iNOS
      and MPO, the contents of NO and MDA were significantly lower while eNOS activity
      was significantly higher in I/R plus sim group than those in I/R group (5.02 +/-
      1.64 vs. 9.19 +/- 2.89, 586.21 +/- 126.97 vs. 744.49 +/- 137.53, 257.72 +/- 93.43
      vs. 384.10 +/- 40.68, 72.10 +/- 18.56 vs. 111.84 +/- 38.58, 7.08 +/- 1.74 vs.
      3.72 +/- 0.98, all P < 0.05). The positive index of NF-kappaB p65 in cardiocytes
      and arteriole at left ventricular wall near the area of myocardial infarction was
      significantly lower in I/R plus sim group than that in I/R group (21.59 +/- 10.5
      vs. 34.32 +/- 9.55, 27.27 +/- 13.19 vs. 44.91 +/- 15.06, each P < 0.05).
      CONCLUSION: Simvastatin could improve myocardial NR after ischemia-reperfusion by
      attenuating endothelial dysfunction and inhibiting inflammation and neutrophil
      activation.

PMID- 19100118
TI  - [Hypoxia/reoxygenation-induced increased activity and expression of PTP-1B in
      neonatal rat cardiomyocytes are mediated by nitric oxide].
AB  - OBJECTIVE: To explore if the hypoxia/reoxygenation-induced increased activity and
      expression of PTP-1B in neonatal rat cardiomyocytes are mediated by nitric oxide
      (NO). METHODS: Neonatal rat cardiomyocytes were isolated and randomly divided
      into 4 groups: normal group (N group); hypoxia/reoxygenation group (H/R group);
      N(omega)-nitro-l-arginine methylester treated group (L-NAME group);
      hypoxia/reoxygenation plus L-NAME group (L-NA + H/R group). PTP-1B activity in
      cardiomyocytes was determined spectrophotometrically at 405 nm, PTP-1B expression
      in cardiomyocytes was detected by Western blot.NO and LDH concentrations in cell
      medium were also assayed. RESULTS: PTP-1B activity and expression in
      cardiomyocytes was significantly higher in the H/R group as compared to the N
      group and this increase could be blocked by cotreatment with L-NAME. As compared
      to H/R group, nitric oxide and LDH concentrations in cell medium were
      significantly decreased in the L-NA + H/R group (NO concentration: H/R group,
      368% +/- 13% and L-NA + H/R group, 61% +/- 7%, P < 0.005; LDH concentration: H/R
      group, 41.2 +/- 6.7 and L-NA + H/R group, 23.6 +/- 4.8, P < 0.05). CONCLUSIONS:
      This study showed that pretreatment with L-NAME, a non-selective inhibitor of
      NOS, prevented the hypoxia/reoxygenation-induced increase in PTP-1B activity and
      expression in cardiomyocytes, suggesting PTP-1B activation during
      hypoxia/reoxygenation was mediated by nitric oxide.

PMID- 19100119
TI  - [Simvastatin attenuated cardiac hypertrophy via inhibiting JAK-STAT pathways].
AB  - OBJECTIVE: To investigate the effects of simvastatin (SIM) on in vivo and in
      vitro cardiac hypertrophy models and changes on JAK/STAT signal pathways.
      METHODS: Myocardial hypertrophy was induced by Cardiotrophin-1 (CT-1) in neonatal
      cardiomyocytes and by abdominal aortic constriction (AC) for 4 weeks in adult SD
      rats. In vitro study groups were as follows (n = 3 each): (1) control, (2) CT-1
      (10(-10) mol/L), (3) CT-1 + SIM (10(-6) mol/L), (4) CT-1 + AG490(JAK inhibitor,
      10(-4) mol/L), (5)SIM (10(-6) mol/L), (6) AG490 (10(-4) mol/L). In vivo study
      groups were as follows (n = 8 each): (1) sham group, (2) AC group, (3) AC + SIM
      group, (4) AC + captopril group. Total protein content was measured by Lowry's
      method and the cell surface area was measured by phase contrast microscope. The
      expression of AGT mRNA and c-fos mRNA were detected by RT-PCR. Systolic blood
      pressure (SBP), heart weight/body weight (HW/BW) and left ventricle weight/body
      weight (LVW/BW) were measured. The expressions of p-JAK2 and p-STAT3 were
      detected by Western blot. RESULTS: The total protein content and cardiomyocytes
      size were significantly increased in CT-1 treated cells and which could be
      blocked by SIM. The expressions of p-JAK2 and p-STAT3 as well as the expression
      of AGT mRNA and c-fos mRNA significantly activated by CT-1, which could be
      inhibited by SIM or Janus Kinase-selective inhibitor AG490. Similar as captopril,
      SIM also attenuated cardiac hypertrophy in AC rats as shown on reduced systolic
      blood pressure, heart weight to body weight, left ventricular weight to body
      weight ratios as well as cross sectional area of cardiomyocytes. CONCLUSION: SIM
      prevented CT-1 and AC induced cardiomyocyte hypertrophy via inhibiting JAK/STAT
      pathways.

PMID- 19100120
TI  - [Renin-angiotensin system blocking agents reverse the myocardial hypertrophy in
      experimental hyperthyroid cardiomyopathy via altering intracellular calcium
      handling].
AB  - OBJECTIVE: To explore the mechanisms of myocardial hypertrophy induced by
      Levothyroxine (L-Thy). METHODS: A rabbit model of hyperthyroidism was established
      by daily intraperitoneal injections of L-Thy (45 microg/kg per day) for 28 days.
      New Zealand rabbits were randomly divided into four groups (n = 10 each): control
      group, L-Thy group (L-Thy alone), imidapril group (L-Thy + 0.5 mg/kg imidapril),
      and valsartan group (L-Thy + 8 mg/kg valsartan). All rabbits were treated for 4
      weeks. At the end of the treatments, all rabbits underwent echocardiography and
      IVS, LV and LVPW thickness were measured. Ventricular tissues were then
      collected.Cardiac hypertrophy index, cardiomyocyte diameter, structural and
      ultrastructural changes were obtained. Ventricular myocytes were isolated by
      enzymatic digestion method and intracellular Ca2+ concentration was determined
      with the fluorescent Ca2+ indicator Fluo3/AM and laser scanning confocal
      microscopy. Activity of Sarco/Endoplasmic reticulum Ca2+ ATPase (SERCA) was
      evaluated with P-NPP method.mRNA expression of L-type Ca2+ channel (LCC),
      ryanodine receptor (RyR), and SERCA was semi-quantified with RT-PCR. Protein of
      IP3R was localized by immunostaining and semi-quantified with pathological image
      analytic system. RESULTS: Compared with control group, rabbits treated with L-Thy
      displayed remarkable myocardial hypertrophy and morphological changes in both
      structure and ultrastructure levels. Increased intracellular Ca2+ concentration
      [(576.2 +/- 41.7) nmol/L vs. (314.6 +/- 35.6) nmol/L, P < 0.01] and decreased
      SERCA activity [(0.062 +/- 0.013) micromol x min(-1)xg(-1) vs. (0.133 +/- 0.022)
      micromol x min(-1)xg(-1), P < 0.01] were detected in L-Thy treated rabbits. RT
      PCR analysis and (or) immunohistochemistry revealed decreased mRNA expression of
      LCC mRNA (0.48 +/- 0.11 vs. 0.75 +/- 0.16, P < 0.01) and increased RyR mRNA (1.19
      +/- 0.21 vs. 0.73 +/- 0.15, P < 0.01), SERCA mRNA (1.01 +/- 0.08 vs. 0.76 +/-
      0.09, P < 0.01) and IP3R protein (65.3 +/- 13.7 vs. 47.9 +/- 10.2, P < 0.01)
      expression in L-Thy treated rabbits. Both imidapril and valsartan could
      significantly attenuate cardiomyocyte hypertrophy and structural remodeling
      induced by L-Thy. Compared with L-Thy group, decreased intracellular Ca(2+)
      concentration [(376.4 +/- 32.5) nmol/L vs. (576.2 +/- 41.7) nmol/L, P < 0.01 and
      (392.6 +/- 41.2) nmol/L vs. (576.2 +/- 41.7) nmol/L, P < 0.01, respectively], and
      increased LCC mRNA (0.68 +/- 0.14 vs. 0.48 +/- 0.11, P < 0.01; 0.64 +/- 0.13 vs.
      0.48 +/- 0.11, P < 0.01, respectively) and SERCA activity [(0.115 +/- 0.019)
      micromol x min(-1)xg(-1) vs. (0.062 +/- 0.013) micromol x min(-1)xg(-1), P <
      0.01; (0.109 +/- 0.015) micromol x min(-1)xg(-1) vs. (0.062 +/- 0.013) micromol x
      min(-1)xg(-1), P < 0.01, respectively] were found in both imidapril and valsartan
      treated rabbits, but expression of RyR, SERCA and IP3R remained unchanged.
      CONCLUSION: Intracellular Ca(2+) overload may play important roles in myocardial
      hypertrophy induced by L-Thy. Imidapril and valsartan may exert beneficial
      effects on hyperthyroid myocardial hypertrophy via altering intracellular calcium
      handling.

PMID- 19100121
TI  - [Evaluation on cardio-ankle vascular index derived from ultrasound].
AB  - OBJECTIVE: The cardio-ankle vascular index (CAVI) could be obtained by measuring
      pulse wave velocity (PWV) and blood pressure (BP). This method is associated with
      various technical drawbacks. We evaluated the accuracy and usefulness of CAVI
      measured by ultrasound via detecting the aortic and ankle flow directly by
      ultrasonic probe. METHODS: CAVI was determined in 96 subjects [64 male, mean age
      (41.2 +/- 8.9) years] who took part in the annual check up program in our
      department by means of the professional equipment (BP-203RPEII, VP-1000, Japan,
      CAVIp), the M-mode (CAVIm) and color Doppler flow imaging (CAVId). Measurement
      reproducibility on was obtained by repeat the measurements in 20 subjects choose
      randomly from the 96 subjects. Carotid ultrasound (CU) was performed to obtain
      intima-media thickness (IMT) and beta index in all subjects. RESULTS: CAVI
      obtained by various methods were similar and comparable (CAVIm 7.74 +/- 1.62,
      CAVId 7.77 +/- 1.59, CAVIp 8.74 +/- 1.57, all P > 0.05). Inter-group and inter
      observer variance was negligible (r1 = 0.98, r2 = 0.97). There were also
      significant correlations between CAVIm and IMT, CAVIm and beta (r1 = 0.824, r2 =
      0.812, all P < 0.01), and between CAVId and IMT, CAVId and beta (r1 = 0.815, r2 =
      0.813, all P < 0.01). CONCLUSIONS: CAVI could be correctly measured by ultrasound
      technique.

PMID- 19100122
TI  - [Transcatheter closure of atrioventricular septal defect: a case report].

PMID- 19100123
TI  - [Transgenic models of dilated cardiomyopathy].

PMID- 19100124
TI  - [Role of nitroxyl hydrogen on normal and failing heart].

PMID- 19100128
TI  - [Should we treat arterial hypertension in the very elderly subjects?].

PMID- 19100130
TI  - [Study of the stroke and coronary risks in hypertensive patients over 54 years of
      age in the primary care practice].
AB  - BACKGROUND AND OBJECTIVES: Quantification of stroke risk is not always performed
      in hypertensive patients in Primary Care. METHODS: This was an epidemiological
      study in hypertensive patients aged 55 years and older attending primary care
      centres in Spain. The D'Agostino Stroke Risk Scale, using data from the
      Framingham Study, was used for assessment of stroke risk. RESULTS: We analysed
      4,945 patients (mean age, 66.8 years; 50.9% females). Mean blood pressure (BP)
      values were 145/86 mmHg in men and 143.7/84.7 mmHg in women (p < 0.001). The
      majority of patients (80.5%) showed high BP values that were above the values
      recommended in the guidelines, despite most of them (89.6%) receiving
      pharmacological antihypertensive treatment. 41% of patients were diabetics. The
      10-year global risk of stroke was 22.5%, and was higher in men (28.6% vs. 16.8%;
      P < 0.001). The risk of stroke increased with age, being more marked in women.
      Several risk factors showed a statistically significant association with the risk
      of stroke. From higher to lower significance, these risk factors were: age, left
      ventricular hypertrophy (LVH), cardiovascular disease, systolic BP, auricular
      fibrillation, diabetes, cigarette smoking, control of BP, gender, and
      antihypertensive treatment. The 10-year coronary risk was higher in men (24.2%
      vs. 16.0%; p < 0.001) and was significantly related to the 10-year risk of stroke
      (r = 0.626). CONCLUSIONS: The risk of stroke in the Spanish hypertensive
      population is high, and is significantly higher in men, although it shows a
      larger age-related increase in women. Linear regression analysis showed a
      moderate, but statistically significant, correlation between coronary risk and
      risk of stroke. Apart from all the variables included in the Framingham Stroke
      Risk Model, gender, control of BP, and antihypertensive treatment accounted
      significantly and independently as calculated risk factors for incidence of
      stroke.

PMID- 19100131
TI  - [Referral to internal medicine for alcoholism: influence on follow-up care].
AB  - BACKGROUND AND AIMS: The problem of high rates of patient drop-out in alcohol
      treatment programs is frequently reported in the literature. Our aim was to
      investigate if internal medicine referral could improve abstinence and retention
      rates in a cohort of alcoholic patients. PATIENTS AND METHODS: A retrospective
      observational study was conducted comparing 200 alcoholic patients attending a
      psychiatric unit (group 1) with 100 patients attending both this unit and an
      internal medicine unit (group 2). We collected sociodemographic and clinical
      variables and analysed differences regarding abstinence and retention rates by
      means of univariate and multivariate analysis. RESULTS: At 3 and 12 months follow
      up, group 2 patients had higher retention and abstinence rates than group 1
      patients. Multivariate analysis including potential confounding variables showed
      that independent predictors of one-year retention were internal medicine referral
      and being married. Independent predictors of one-year abstinence were being
      married, age > 44 years and receipt of drug treatment. CONCLUSIONS: The higher
      retention rate found among patients referred to Internal Medicine specialists, a
      result that has not been previously reported to the best of our knowledge,
      emphasizes the importance of a multidisciplinary team approach in the treatment
      of alcoholism.

PMID- 19100132
TI  - [Clinical course and features of the alcohol withdrawal syndrome in a general
      hospital].
AB  - INTRODUCTION: Despite its frequency and high clinical burden, few studies have
      analyzed the clinical features of the alcohol withdrawal syndrome in a hospital
      setting. Our purpose was to describe its manifestations and clinical course in a
      general hospital. PATIENTS AND METHODS: Patients with a diagnosis of alcohol
      withdrawal since January 1983 to December 2003, according to the revised fourth
      edition of the Diagnostic and Statistical Manual of Mental Disorders criteria, at
      the Xeral-Calde General Hospital in Lugo, were studied. Clinical and biochemical
      data at admission were collected, as well as those referred to the clinical
      course and complications. RESULTS: 539 episodes in 436 patients were included.
      Mean age was 45 (standard deviation: 12), and 91,3% were men. Abstinence was the
      reason for admission in 62,3%. 71,1% had a diagnosis of delirium tremens during
      their stay. Hallucinations were present in 59,7%, and convulsions (most of them
      generalized) in 41%. Patients with delirium tremens had greater elevations in
      temperature, heart rate and blood pressure, as well as more convulsions than
      minor withdrawal cases. Cirrhosis was present in 10%. The admission rate to the
      Intensive Care Unit (ICU) was 37,8% (95% confidence interval [95%IC]: 33,1-37,8).
      Of these, 69,9% needed mechanical ventilation. Mortality rate was 6,6% (95%IC:
      4,2-9,1). 62% of patients died after admission in the ICU. CONCLUSION: The
      majority of complications related to the alcohol withdrawal syndrome in a
      hospital setting develop in patients with delirium tremens. They are especially
      related to the rate of admissions to the ICU and the use of mechanical
      ventilation.

PMID- 19100134
TI  - [Contrast nephropathy. Review and prophylaxis].
AB  - The use of diagnostic techniques with iodinated contrast media represents a
      regular medical practice. Contrast induced nephropathy is a rare complication in
      the general population but it has an important prevalence and morbidity in
      selective groups of patients. Its multifactorial pathogenesis has not yet been
      totally determined. Identification of high-risk patients and early application of
      suitable preventive measures is crucial. The following article summarizes the
      most important aspects of this entity and the possibilities for its prevention.

PMID- 19100133
TI  - [Prevalence and risk of developing heart failure in hypertensive patients managed
      in Spanish primary care centres. HICAP study].
AB  - OBJECTIVE: The objective was to establish the proportion of hypertensive patients
      diagnosed with heart failure (HF) and at high risk of developing it in Primary
      Care (PC) centres in Spain. METHODS: Observational, multicentre study. Each
      investigator included data from 5 consecutive hypertensive patients. A routine
      laboratory test and a electrocardiogram performed in the previous 6 months had to
      be available for each patient. RESULTS: Data from 6,375 patients were suitable
      for the study objectives. The proportion of patients diagnosed with HF was 18.9%
      (95% confidence interval: 17.97-19.90%), and increased with age. Among the
      patients not previously diagnosed with HF, 59.1% (95%CI: 57.7-60.5%) had a high
      risk of developing it. Blood pressure and other cardiovascular risk factors
      control in high risk patients was insufficient. CONCLUSION: The proportion of
      hypertensive patients diagnosed with HF and at high risk for developing it is
      high in PC. Blood pressure and other cardiovascular risk factors control should
      be improved to avoid the development of HF among high risk patients.

PMID- 19100135
TI  - [Imaging tests in acute abdominal pain].
AB  - Acute abdominal pain constitutes a diagnostic challenge for the physician. The
      list of diseases that can cause abdominal pain is very extensive. Some of these
      conditions may be serious and life-threatening. The medical history is
      fundamental for the judicious choice of the most suitable diagnostic tests. Plain
      abdominal x-ray has little diagnostic efficiency although it comprises the
      initial diagnostic test when perforation of a hollow viscus, intestinal
      obstruction or ingestion of a foreign body is suspected. Abdominal ultrasound is
      the test of choice in suspected biliary tract pathology, complicated renal colic
      and gynaecological disease. Abdominal computed axial tomography (CT) may be the
      most sensitive and specific imaging test for diagnosing most causes of abdominal
      pain but should be reserved for selected cases.

PMID- 19100129
TI  - [The ZANyCONTROL study. The role of the pharmacy].
AB  - OBJECTIVE: To compare blood pressure levels measured in the pharmacy with those
      obtained in the patient's home or Primary Care centres (doctor's surgery or
      treatment room). METHOD: Multicentre, open-label, observational, and medium-term
      follow-up study. LOCATION: Primary Care in the Spanish healthcare system.
      PARTICIPANTS: 206 general or family practitioners who consecutively selected a
      maximum of 10 patients each; 1,588 patients were recruited. INTERVENTIONS AND
      MAIN MEASUREMENTS: Home blood pressure (BP)monitoring, measurements taken in
      clinics (doctor's surgery and treatment room) and pharmacies (usual apparatus and
      validated Omrom M4); ambulatory monitorization was performed on 190 patients
      (model Spacelab 90207). RESULTS: 1,399 patients were included (50.4% women), with
      a mean age of 60.1 (standard deviation [SD]: 9.7) years. BP values obtained in
      doctor's surgeries were significantly higher than those obtained in treatment
      rooms, pharmacies and at home (P < 0.01 in all cases). The smallest differences
      were observed between the pharmacy and home measurements, with 0.69 (SD: 8.1) for
      the systolic BP (p = 0.007) and 0.15 (SD: 5.48) for diastolic BP (p = 0.370).
      DISCUSSION: The ZANyCONTROL study supports the idea that BP measurements taken on
      hypertensive patients in the pharmacy properly reflect their real BP; it is an
      accessible and effective method for measuring blood pressure. It is important
      that the sphygmomanometer in the pharmacy is validated and works correctly.

PMID- 19100136
TI  - [52-year old male with tumour and pain in the left hemithorax].

PMID- 19100137
TI  - [84-year old woman with necrotic ulcer on the left lower limb].

PMID- 19100138
TI  - [Acute abdomen in a 54-year old patient].

PMID- 19100139
TI  - [Purulent pericarditis as a complication of bacteraemic pneumococcal pneumonia].

PMID- 19100140
TI  - [On the term "pathology" in the acceptance of "disease"].

PMID- 19100141
TI  - [Erythema nodosum and tularaemia].

PMID- 19100142
TI  - [Pure red cell aplasia secondary to carbamazepine].

PMID- 19100143
TI  - [What can really be done to reduce the number of clinic visits by the frequent
      user patient?].

PMID- 19100144
TI  - [Changes in the tetanus vaccination guidelines?].

PMID- 19100145
TI  - [Conciliation discrepancies at hospital discharge].
AB  - OBJECTIVE: To evaluate and describe the non-justified discrepancies found on
      reconciling chronic medication prescribed to patients when discharged from
      hospital. Secondly, the impact of the reconciliation process is evaluated by
      assessing the seriousness of the discrepancies. DESIGN: Cality study. SETTING:
      Short Stay Medical Unit in Elda General Hospital, Alicante, Spain. PARTICIPANTS:
      All patients discharged were included. INTERVENTION: The medication that the
      patient was taking before admission was obtained by personal interview before
      being discharged. The discrepancies that were non-justifiable with the treatment
      on discharge and with the pharmacotherapeutic history were identified and
      modified, where necessary, after consulting with the doctor. MEDITIONS AND
      RESULTS: Of the 434 patients interviewed, 249 conciliation errors were detected,
      which was 0.57 discrepancies per treated patient. Among the 35.2% of patients who
      had conciliation errors, the mean number of discrepancies was 1.62. Of these
      errors, 153 (61.5%) were produced when being discharged, while 96 (38.5%) were
      errors of omission or commission in the pharmacotherapeutic history. Of all the
      discharge reports reviewed, 11% did not record information on the previous
      treatment of the patient. Omission was the main type of error, both in the
      history and on discharge. As regards the potential harm of the detected errors,
      30% could have caused temporary harm or hospitalisation. CONCLUSION: Medication
      errors in the pharmacotherapeutic history at the time of being admitted are
      common and potentially significant if they are continued. Including the
      pharmacist in the medical team, along with being able to access data at the
      different care levels, could help to reduce the frequency of these errors.

PMID- 19100146
TI  - [Commentary: medication reconciliation at hospital admission and discharge: a
      multidisciplinary challenge].

PMID- 19100147
TI  - [Influence of morbidity and the use of health resources in patients who require
      care for generalised anxiety disorder in the primary health care setting].
AB  - OBJECTIVE: To evaluate the co-morbidity, health care use, economical impact, and
      availability of effective treatments used in generalised anxiety disorder (GAD)
      patients in a primary care setting (PCS). METHOD: A retrospective multicentre
      population-based study. SETTING: Five primary care clinics managed by Badalona
      Serveis Assistencials S.A., Barcelona, Spain. PARTICIPANTS: Outpatient records of
      patients over 18 years managed at 5 PCSs during 2006. Patients with and without
      GAD were compared. In GAD patients, 4 groups were established for comparison,
      according to pharmacological prescription. MEASUREMENTS: Main outcomes measures
      were general, reason/co-morbidity, health care use and primary care cost (visits,
      diagnostic/therapeutic tests, and drugs). We counted work absenteeism as an
      indirect cost. Pharmacological prescription was studied according to evidence
      based recommendations and Spanish health-approved indications. The statistical
      analysis included a multivariate model: logistic regression, analysis of
      covariance (ANCOVA), P< .05. RESULTS. Of the 65 767 patients included, 4.6% (95%
      confidence interval [CI], 3.9-5.3) had GAD. Patients with/without GAD, the
      average episode/year was 6.1 versus 4.7 and attendance/year 10.0 versus 7.6; P<
      .001. GAD was associated with women (odds ratio [OR], 1.8), dyslipidemia (OR,
      1.2), smoking (OR, 1.4), depression (OR, 1.2), and cerebrovascular accident (OR,
      1.6) (P< .02). The mean direct cost/year adjusted by age, gender and morbidity
      load was euro686 versus euro557 (P< .001). GAD was associated with higher directs
      costs. The recommended treatment was followed in 40.1% of total patients (95% CI,
      38.4-41.8). CONCLUSIONS: Patients with GAD have greater co-morbidity and higher
      direct costs in PCS. Means designed to improve the recognition and treatment of
      these patients should be established in the PCS.

PMID- 19100148
TI  - [Adaptation of a patient satisfaction questionnaire on medical and nursing care].
AB  - OBJECTIVE: Catalan and Spanish adaptation of a questionnaire to measure patient
      satisfaction with their family doctor and nurse visit. DESIGN: Descriptive study
      of adapting questionnaires. SETTING: Primary Care Team Gotic, Institut Catala de
      la Salut, Barcelona, Spain. PARTICIPANTS: Of all the patients visiting doctors or
      nurses, 1186 patients were systematically selected. Of these, 341 were excluded
      using the following criteria: illiteracy, not understanding either language,
      cognitive impairment, sight, or writing disability. MEASUREMENTS: Two
      translations of the original questionnaire. Analysis of the pattern of response.
      Exploratory factor analysis. Correlation item-scale corrected coefficients and
      Cronbach alpha for each dimension. RESULTS: There were 74.8% responses. The
      percentage of items not answered follows a pattern of declining response. There
      were 3 dimensions in the factor analysis: care offered by the professional, time
      devoted to the visit, and depth of the relationship with the professional, where
      the items weighed the same as in the original questionnaire, except two of them.
      The item-dimension correlation coefficients were greater than 0.4 except for
      items number 8 and number 18. The coefficient of internal consistency proved to
      be greater than 0.7 in all dimensions except in "depth of the relationship,"
      which rises above 0.7 if item number 8 is excluded. CONCLUSION: Adaptation of a
      valid and reliable questionnaire into Spanish and Catalan is useful for
      evaluating aspects of the professional care visit.

PMID- 19100149
TI  - [Increased benzodiazepine use in elderly women attending urban primary health
      care centers].
AB  - OBJECTIVE: To determine the overall prevalence of the chronic use of
      benzodiazepines and similar drugs in primary care. DESIGN: Observational, cross
      sectional study. SETTING: Healthcare centres of the Reus-Altebrat Primary Care
      Service, Tarragona, Spain. PARTICIPANTS: Patients older than 15 years, on
      prolonged treatment with benzodiazepines or similar drugs. MEASUREMENTS: The
      variables studied were age, sex, type of healthcare centre (rural or urban),
      benzodiazepine, or similar drug administered and duration of treatment. RESULTS.
      There were 6885 patients who were on prolonged benzodiazepine or similar drug
      treatment, of which 70.9% were female, 73.4% were 65 years or older, and 73%
      attended an urban centre. The overall prevalence was 6.9%, and was higher among
      women than men (9.7% and 4%, respectively), and increased with age up to 27.3%
      among patients of 75 years or more. The stratified results showed that chronic
      consumption was higher among women 75 years of age or older attached to urban
      healthcare centres, with a prevalence of 35.7%. CONCLUSIONS: A high percentage of
      our population, which includes the most fragile patients, use benzodiazepines or
      a similar drug in a way that is not consistent with the recommendations of
      clinical practice guidelines.

PMID- 19100150
TI  - [Cardiovascular events in patients with hidden renal failure detected by
      equations of glomerular filtration].
AB  - OBJECTIVE: The objective of this work was to value the relationship between
      cardiovascular disease and presence of hidden renal failure in patients between
      35 and 74 years followed up for 10 years. DESIGN: Observational, longitudinal,
      retrospective study of a cohort of patients. SETTING: Primary care health centre.
      PARTICIPANTS: We studied 875 patients (average age, 55.6 years, with 57.4% women)
      without evidence of cardiovascular disease, cared for in an urban primary health
      centre. MEASUREMENTS AND MAIN RESULTS: Glomerular filtration was estimated using
      Cockcroft-Gault and simplified MDRD equations. Hidden renal failure was
      considered if the glomerular filtration was <60 mL/min with a normal serum
      creatinine concentration. Using the Cockcroft-Gault equation 11.2% of study
      population had hidden renal failure and 12% when using MDRD, and 16.3% of
      patients with hidden renal failure using Cockcroft-Gault equation had coronary
      events. The relative risk in this group was 1.8 (95% confidence interval [CI],
      1.1-2.9; P< .05). The percentage of coronary events was 16.2% when glomerular
      filtration was estimated by MDRD (relative risk, 1.9; 95% CI, 1.2-3.1; P< .05).
      Binary logistic regression analysis showed that age, male sex, smoking, diabetes,
      and diastolic pressure were the predicting variables of cardiovascular events,
      the highest odds ratio corresponding to the smoking population. The presence of
      hidden renal failure was not statistically significant using either Cockcroft
      (odds ratio, 1.21; 95% CI, 0.64-2.28; P=.566) or MDRD (odds ratio, 1.64; 95% CI,
      0.77-3.48; P=.200) CONCLUSIONS: The prevalence of occult renal dysfunction in the
      35-74 years population is high, but it does not behave as an independent
      cardiovascular risk factor.

PMID- 19100151
TI  - [Frequent user patients in primary care: sociodemographic profile, clinical
      characteristics, and a proposed new definition].

PMID- 19100152
TI  - [Reflections on the health system of the city of Sao Paulo and Catalonia:
      description of the Brazil and Sao Paulo health model (I)].

PMID- 19100153
TI  - [1st conference on health prevention and promotion in clinical practice in Spain.
      Prevention of childhood and juvenile obesity].

PMID- 19100154
TI  - [Intestinal parasitic infections in a Valencia school population].

PMID- 19100155
TI  - [Role of nurses in emergency triage in primary care].

PMID- 19100156
TI  - [Assessment of joint mobility, muscular shortening, and joint decompensation].

PMID- 19100157
TI  - [The clinical question: a powerful and unexpected training opportunity].

PMID- 19100158
TI  - [Diagnosis disagreements between general physicians and psychiatrists].

PMID- 19100160
TI  - [Analysis of the results of the SEIMC External Quality Control Program, 2007].
AB  - The External Quality Control Program of the Spanish Society of Infectious
      Diseases and Clinical Microbiology (SEIMC) includes controls for bacteriology,
      serology, mycology, parasitology, mycobacteria, virology and molecular
      microbiology. This article presents the most important conclusions and lessons
      drawn from the 2007 controls. As a whole, the results obtained in 2007 confirm
      the excellent skill and good technical standards found in previous years.
      However, erroneous results can be obtained in any laboratory and in clinically
      relevant determinations. A few deviations were observed in some controls, calling
      for critical reflection. Once again, the results of this program highlighted the
      need to complement internal with external controls, such as those offered by the
      SEIMC program.

PMID- 19100161
TI  - [Analysis of the results of the SEIMC External Quality Control Program for HIV-1
      and HCV viral loads, 2007].
AB  - BACKGROUND: Human immunodeficiency virus type 1 (HIV-1) and hepatitis C virus
      (HCV) viral load determinations are among the most important tasks performed in
      the molecular microbiology laboratory, due to their importance in patient follow
      up. Quality control tools are crucial in these laboratories to ensure the
      accuracy of the results. This article presents the analysis of the results
      obtained in 2007 from the SEIMC External Quality Control Program for HIV-1 and
      HCV viral loads. METHODS AND RESULTS: In the HIV-1 program, a total of five
      standards were sent. One standard consisted of seronegative human plasma, while
      the remaining four contained plasma from three different viremic patients, in a
      range of 2-5 log(10) copies/mL; to analyze repeatability, two of these standards
      were identical. The specificity was good for all the methods used by the
      participants, and only two out of 75 results were considered to be false positive
      results. A substantial proportion of the laboratories (20% on average) obtained
      values outside the accepted range (mean +/-0.2 log(10) copies/mL), depending on
      the standard and on the method used for quantification. A few errors were due to
      the transcription of the analytical result. Repeatability was also acceptable but
      approximately 15% of laboratories failed this evaluation. The HCV program
      consisted of two standards with different viral load contents. Most of the
      participants (94.6%) obtained results within the accepted range (mean +/-1.96 SD
      log(10) UI/mL), and interlaboratory variability was <0.5 log units for both
      standards and all techniques. CONCLUSIONS: Data from this analysis reinforce the
      utility of proficiency programs to ensure the quality of the results obtained by
      a particular laboratory, as well as the importance of the post-analytical phase
      in overall quality. Due to wide interlaboratory variability, the use of the same
      method and the same laboratory for patient follow-up is advisable.

PMID- 19100162
TI  - [Diagnosis of streptococcal pharyngitides].
AB  - Tonsillitis and pharyngitis are highly frequent infections in Spain with multiple
      causes, especially viruses. Etiologic diagnosis of pharyngitis is only important
      in Streptococcus pyogenes or group A beta-hemolytic streptococcal infections
      because antibiotic therapy is mandatory to prevent further complications,
      especially acute rheumatic fever. Diagnosis has classically been based on
      bacterial isolation from throat swabs. There are no standardized methods for this
      culture in terms of culture medium, incubation atmosphere or the identification
      tests to be performed. Currently, a large number of commercial reagents are
      available, which, through different immunological techniques, allow direct
      antigen detection in the clinical sample. Most of these products show good
      sensitivity and specificity values, with the added advantage of providing a rapid
      result, especially if they are performed at points of care. Many guidelines for
      the management of patients with pharyngitis and tonsillitis are available.
      Nevertheless, as antigen detection results can vary in each center according to
      the indications and the care taken in sample extraction, the method chosen should
      be evaluated before implementation.

PMID- 19100163
TI  - [Community-acquired methicillin-resistant Staphylococcus aureus].
AB  - Recently, methicillin-resistant Staphylococcus aureus (MRSA) has emerged as a
      cause of community-acquired (CA) infections among patients without established
      risk factors for MRSA. CA-MRSA strains mainly cause mild skin and soft tissue
      infections in otherwise healthy children and young adults, but can also cause
      severe necrotizing fasciitis and pneumonia. In contrast to nosocomial MRSA, CA
      MRSA are, in general, susceptible to multiple antimicrobials and present a
      different genotype. Most CA-MRSA strains share the staphylococcal chromosomal
      cassette (SCCmec) type IV and produce Panton-Valentine leukocidin (PVL), a
      cytotoxin that causes leukocyte destruction and tissue necrosis. At present, the
      predominant clone is the USA300 clone, which is widely disseminated in the United
      States, Europe and Australia. In Spain, the predominant clone is related to the
      USA300 clone. The main mechanism of transmission is close person-to-person
      contact, although household pets and farm animals have also been implicated. In
      patients with purulent skin and soft tissue infections, the mainstay of treatment
      is incision and drainage. Antimicrobials are indicated in patients not responding
      to appropriate drainage. Clindamycin, trimethoprimsulfamethoxazole or
      tetracyclines can be administered, while the use of fluoroquinolones should be
      avoided due to the rapid emergence of resistance. For severe infections,
      vancomycin should be used. Other alternatives are linezolid or daptomycin (only
      if there is no pulmonary involvement). Adequate hygiene practices are the most
      efficient measure to prevent spread.

PMID- 19100164
TI  - [Update on the epidemiology, diagnosis and treatment of sexually-transmitted
      infections].
AB  - In the last decade, cases of sexually-transmitted infections (STIs) have
      progressively increased in Europe. The reasons for this increase are unclear, but
      may involve changes in social behavior, migration and international travel,
      coupled with the emergence of risk groups that have not been taken into
      sufficient consideration to date. The routine use of molecular diagnostic
      techniques for many of these infections has solved many problems of sensitivity
      and the suitability of samples for microbiological diagnosis: non-invasive
      samples can be used, which has undoubtedly contributed to the increase in the
      number of cases. Moreover, molecular methods have also been introduced for
      antibiotic and antiviral susceptibility testing, as well as for molecular
      characterization of clinical isolates. All of these factors, together with the
      approval of the vaccine against the human papillomavirus, have changed the
      landscape of STIs across Europe.

PMID- 19100165
TI  - [Infections related to recreational waters].
AB  - Recreational waters are a source of infection by several microorganisms causing
      acute gastrointestinal, cutaneous and respiratory illnesses. Cryptosporidium,
      noroviruses and enteropathogenic Escherichia coli strains are the most important
      causes of diarrhea, while Pseudomonas and Staphylococcus aureus are the main
      causes of cutaneous infections, and Legionella is the major cause of acute lower
      respiratory disease. Approximately 90% of outbreaks occur in treated recreational
      waters (swimming pools, spas and recreational parks), while the remaining 10%
      arise from natural waters used for leisure (bathing in rivers, beaches, etc). In
      spas, most infections are caused by thermophilic bacteria, such as Pseudomonas
      and Legionella, since overgrowth of these bacteria is facilitated by the direct
      effect of temperature and, indirectly, by the evaporation of the disinfectant.
      Outbreaks related to recreational waters usually reflect deficient control of the
      system: a low level of disinfectant, or the use of an inappropriate disinfectant,
      insufficient maintenance and cleaning of the installation, higher than
      recommended usage, and failure of the disinfectant dosage system. The correct
      design, maintenance and use of these facilities drastically lower the risk of
      infections from recreational waters. Thus, other key actions to minimize this
      risk are the existence of, and compliance with, regulatory rules, as well as
      educational campaigns on good hygiene practices directed at users. Rapid
      etiologic diagnosis of affected patients, together with an epidemiological survey
      and detection of the pathogen implicated in water samples are the keys to
      outbreak control.

PMID- 19100166
TI  - [Advances in the diagnosis and treatment of yeast infections: role of the new
      antifungal agents].
AB  - Invasive candidiasis has become a public health problem due to the high
      associated rates of morbidity and mortality. As in other systemic infections,
      accurate and early diagnosis is essential. Despite its limited sensitivity (50%),
      blood culture continues to be the most effective technique for the diagnosis of
      candidemia. New culture-independent techniques have been marketed with the aim of
      improving diagnostic yield. Among these techniques, the most notable are (1-3)
      beta-D-glucan and anti-germ-tube antibody detection. However, the best option to
      optimize the diagnosis of invasive candidiasis seems to be the combination of two
      techniques that detect antigen, antibodies, (1-3)-beta-D-glucan or DNA.
      Fluconazole, and sometimes amphotericin B, remain the antifungal agents of choice
      for the treatment of candidiasis. In the last few years, new antifungal agents
      have been introduced with the aim of improving the prognosis of some clinical
      presentations of this disease. The echinocandins and second-generation triazoles
      show greater antifungal activity than fluconazole. Moreover, clinical trials of
      candidiasis in different localizations have shown that these drugs have excellent
      efficacy and safety profiles. The potential for drug interactions with some of
      these antifungal agents is considerable. The contribution of the new antifungal
      drugs in the treatment of candidiasis should be defined in the near future.

PMID- 19100167
TI  - [Molecular techniques in mycology].
AB  - An increasing number of molecular techniques for the diagnosis of fungal
      infections have been developed in the last few years, due to the growing
      prevalence of mycoses and the length of time required for diagnosis when
      classical microbiological methods are used. These methods are designed to resolve
      the following aspects of mycological diagnosis: a) Identification of fungi to
      species level by means of sequencing relevant taxonomic targets; b) early
      clinical diagnosis of invasive fungal infections; c) detection of molecular
      mechanisms of resistance to antifungal agents; and d) molecular typing of fungi.
      Currently, these methods are restricted to highly developed laboratories.
      However, some of these techniques will probably be available in daily clinical
      practice in the near future.

PMID- 19100168
TI  - [Multidrug-resistant tuberculosis].
AB  - The emergence and spread of Mycobacterium tuberculosis strains resistant to
      multiple drugs represent a threat for global tuberculosis control. The World
      Health Organization (WHO) estimates that almost 500,000 cases of M. tuberculosis
      resistant to isoniazid and rifampicin (multidrug-resistant, or MDR-TB), at least,
      emerged in 2006. In addition, new cases of extensively drug-resistant
      tuberculosis (XDR-TB), defined as MDR-TB with resistance to a fluoroquinolone and
      at least one second line injectable agent, have been reported in 45 countries in
      all five continents. Multidrug-resistant tuberculosis is an emerging problem in
      Spain but the impact of this disease is limited: the WHO estimates that 0.1% of
      new cases of tuberculosis and 4.3% of previously treated cases are MDR-TB.
      Treatment of MDR-TB is especially complicated, since this disease requires the
      use of drugs that are less effective and more toxic, requiring treatment to be
      administered over longer periods and severely reducing the probability of
      success. This situation poses a serious problem for low income countries,
      especially those with a high prevalence of human immunodeficiency virus type 1
      (HIV-1) infection. MDR-TB and XDR-TB are also of special concern in wealthy
      countries, due to mass immigration. Therefore, tuberculosis resistant to multiple
      drugs should be given high priority in global public health and biomedical
      research.

PMID- 19100169
TI  - [Rotavirus and other viruses causing acute childhood gastroenteritis].
AB  - Acute gastroenteritis is one of the most common diseases, affecting children
      worldwide. Viruses are recognized as a major cause of this disease, particularly
      in children. Since the Norwalk virus was identified as a cause of
      gastroenteritis, the number of viral agents associated with diarrheal disease in
      humans has progressively increased. Rotavirus is the most common cause of severe
      diarrhea in children under 5 years of age. Human astroviruses, caliciviruses and
      enteric adenovirus are also important etiologic agents of acute gastroenteritis.
      Other viruses such as toroviruses, coronaviruses, picobirnaviruses, Aichi virus
      and human bocavirus are increasingly being identified as causative agents of
      diarrhea. Vaccination against rotavirus could prevent cases of severe diarrhea
      and reduce the mortality attributable to this disease.

PMID- 19100170
TI  - [Diagnosis of HIV-1 non-B subtypes and HIV-2].
AB  - The high genetic diversity of human immunodeficiency virus (HIV) poses a
      significant challenge to the diagnosis and microbiological characterization of
      HIV infection. Because of the continual emergence of new variants and the global
      spread of HIV groups, subtypes and recombinant forms, accurate diagnostic tools
      are of prime importance. The present review analyzes the problems posed by HIV
      assays for antibody screening, nucleic acid testing and patient monitoring in HIV
      1 non-B subtypes, as well as the utility of some recently introduced genetic
      algorithms, such as those proposed for the characterization of viral tropism.
      Overall, the reliability of serological and molecular tests for HIV-1 strains is
      high, except for the more genetically diverse HIV variants (HIV-1 group O, N, and
      HIV-2). In contrast, genetic algorithms show acceptable accuracy for HIV-1
      subtype B, but are less accurate for non-B subtypes. In conclusion, the ongoing
      evolution of HIV requires constant monitoring of the performance of screening
      tests and provides a stimulus to the development of molecular assays to detect
      all spreading and emerging HIV variants. The availability of both in vitro and
      clinical data from studies of HIV-1 non-B subtypes will improve the performance
      of bioinformatics tools.

PMID- 19100171
TI  - [Extrapulmonary tuberculosis: situation in the new century].

PMID- 19100172
TI  - [Genitourinary mycobacteriosis: retrospective study of 45 cases in a general
      hospital].
AB  - INTRODUCTION: Genitourinary tuberculosis (GUT) is the third most frequent
      extrapulmonary tuberculous infection, following pleural and nodal involvement.
      Associated clinical symptoms are mild, and the diagnosis and treatment of this
      condition are often delayed. METHODS: This study determines the clinical and
      epidemiological characteristics, and outcome of patients diagnosed with GUT in
      our center over the last 10 years. Patients with positive Lowenstein-Jensen urine
      or biopsy culture, or pathologic study suggestive of tuberculosis were included.
      Cases of multifocal tuberculosis and positive Lowenstein-Jensen, but with no
      urinary symptoms or radiological alterations, were considered to have
      mycobacteriuria. RESULTS: Forty-five patients were analyzed (62% men; mean age,
      49.4 years). Among the total, 33% had a coexisting disease (14 were infected by
      human immunodeficiency virus). Twenty-six patients (57%) had renal tuberculosis,
      5 (11%) orchiepididymitis, and 14 (31%) were classified as having
      mycobacteriuria. The most frequent clinical manifestations were urination
      syndrome (61%), low back pain (44%), and macroscopic hematuria (12%). Ziehl stain
      was positive in 38% cases. Urine culture was positive for other microorganisms in
      9 patients (20%). Intravenous urography oriented the diagnosis in 87.5% of cases.
      The average interval between onset of symptoms and diagnosis was 15 months. Cure
      without sequelae was obtained in 60%. Surgery was indicated in 10 patients.
      CONCLUSIONS: The index of suspicion for GUT should be high when patients present
      with repeated urinary syndromes. The current use of imaging studies other than
      urography and the finding of other microorganisms in urine culture can delay the
      diagnosis.

PMID- 19100174
TI  - [Fresh versus pasteurized yogurt: comparative study of the effects on
      microbiological and immunological parameters, and gastrointestinal comfort].
AB  - OBJECTIVE: To determine whether the beneficial effects of yogurt are dependent on
      the viability of lactic bacteria and exclusive to fresh yogurt, by comparison
      with the effects of yogurt that is pasteurized after fermentation. MATERIAL AND
      METHOD: Using a double-blind design in a healthy adult population over 75 days,
      we compared the effects of fresh and pasteurized yogurt on microbiological
      (presence of viable bacteria in yogurt and DNA detection in feces) and
      immunological (nephelometry, hematometry, and flow cytometry) parameters. A
      questionnaire was used to assess gastrointestinal comfort. Differences in lactose
      absorption after ingestion of fresh or pasteurized yogurt were determined by
      breath hydrogen analysis. RESULTS: There were no significant differences in the
      results obtained for microbiological or immunological parameters,
      gastrointestinal comfort, or lactose test between the two types of yogurt
      ingested. Lactobacillus delbrueckii ssp. bulgaricus (L. bulgaricus) was isolated
      in 0.7% of the fecal samples analyzed. Streptococcus thermophilus was not found
      in any sample. DNA from lactic bacteria was detected in only 12.5% of the samples
      analyzed. CONCLUSION: Transit through the gastrointestinal tract affects survival
      of L. bulgaricus and S. thermophilus. No differences were found in the
      immunological parameters, gastrointestinal comfort, or lactose overload after
      intake of fresh or pasteurized yogurt.

PMID- 19100173
TI  - [Use of non-occupational HIV post-exposure prophylaxis in Spain (2001-2005)].
AB  - BACKGROUND: Non-occupational post-exposure prophylaxis for human immunodeficiency
      virus (HIV) infection is widely used, although there is little available
      scientific evidence to support its effectiveness. The aim of this study is to
      describe the characteristics of the persons exposed, types of exposures,
      antiretroviral treatment prescribed, and outcome of HIV infection in cases of non
      occupational exposure in Spain. METHOD: The data used included all cases of
      accidental HIV exposure notified to the Non-occupational Post-exposure
      Prophylaxis Information System between January 2001 and December 2005. Non
      occupational exposure to HIV was defined as accidental contact with blood and/or
      other biological fluids outside the healthcare setting. RESULTS: A total of 993
      cases of exposure were notified (569 men [57.3%]); median age was 30 years
      (range: 1-87). Exposure was sexual in 53.1%, parenteral in 39.8%, and other types
      in 7.2%. The source person was identified in 82.7% of cases. Antiretroviral
      treatment (ART) was prescribed in 528 cases (53.2%), with triple therapy in
      68.2%. A total of 54.2% returned for the 6-month visit among patients receiving
      ART and 61.1% among those without this therapy (P < 0.05). One or more side
      effects developed in 135 (32.4%) cases, and there were 18 treatment interruptions
      (4.3%). Three seroconversions to HIV were notified (0.3%). CONCLUSIONS: A
      national registry for monitoring non-occupational post-exposure prophylaxis to
      HIV is needed because of the high number of cases notified, the considerable
      incidence of side effects, and the difficulties of follow-up.

PMID- 19100175
TI  - [Cyclospora cayetanensis outbreak in travelers to Cuba].
AB  - Initially described in travelers, outbreaks of cyclosporiasis were soon linked to
      imported food products. An outbreak of cyclosporiasis in Spanish travelers is
      described. After identification of Cyclospora cayetanensis in stool analyses, a
      specific questionnaire was completed. Pyrosis was described in 57% of cases
      (4/7). Peptic symptoms can be a useful clue to indicate the diagnosis of
      cyclosporiasis in patients with travelers' diarrhea.

PMID- 19100176
TI  - [Relationship between hepatic fibrosis measured by transient elastography and
      peripheral blood CD4+ lymphocyte values].
AB  - Advanced hepatic fibrosis decreases absolute CD41 lymphocyte count in HIV
      infected patients. The correlation between hepatic stiffness measured by
      transient elastography and absolute CD41 lymphocyte count is unknown. Analysis of
      the correlation between transient elastography parameters and absolute CD41
      lymphocyte count in 223 HIV-infected patients with chronic viral hepatitis. As
      compared to patients without significant fibrosis, absolute CD41 cell count was
      lower in patients with significant hepatic fibrosis (384 cel/microL vs. 431
      cel/microL; P = 0.023) and in patients with advanced hepatic fibrosis (330
      cel/microL vs. 431 cel/microL; P = 0.002). There is a significant association
      between hepatic stiffness measured by transient elastography and absolute CD41
      lymphocyte count in HIV-infected patients with chronic viral hepatitis.

PMID- 19100177
TI  - [Classic vaccinology and advances in vaccine design].
AB  - The prevention of many infectious diseases, allergies, autoimmune diseases, and
      cancer continues to be a challenge in the twenty-first century. Nonetheless,
      considerable advances have already been made, such as the eradication of certain
      infectious diseases and effective control of many others, and new technology is
      being developed in areas related to molecular biology, recombinant DNA, protein
      biochemistry, microbiology, and immunology. The current trends point to continued
      progress in coming years. Technical skills will become highly refined, so that
      any antigen or epitope can be presented in a highly immunogenic form within a
      vaccine. Modern technology has led to the formulation of a new paradigm in
      vaccine development, in which the genomic and/or proteomic aspects of diseases
      are analyzed a priori to identify factors implicated in the immune response that
      may serve as promising vaccine candidates.

PMID- 19100178
TI  - [Microbiological diagnosis of emerging bacterial pathogens: Anaplasma,
      Bartonella, Rickettsia, and Tropheryma whipplei].
AB  - Ehrlichia/Anaplasma, Bartonella, Rickettsia and Tropheryma whipplei (formerly
      called whippelii) are fastidious bacterial organisms, considered the causative
      agents of potentially severe emerging and re-emerging diseases with repercussions
      on public health. The recent availability of advanced molecular biology and cell
      culture techniques has led to the implication of many of these species in human
      pathologies. These issues are extensively covered in number 27 of the SEIMC
      microbiological procedure: Diagnostico microbiologico de las infecciones por
      patogenos bacterianos emergentes: Anaplasma, Bartonella, Rickettsia y Tropheryma
      whippelii (Microbiological diagnosis of Anaplasma, Bartonella, Rickettsia and
      Tropheryma whippelii infections) (2nd ed., 2007)
      (www.seimc.org/documentos/protocolos/microbiologia/).

PMID- 19100179
TI  - [Eye infections associated with ocular implants].
AB  - Postoperative endophthalmitis associated with intraocular lens implantation is
      one of the most severe complications of cataract surgery. The prevalence of
      endophthalmitis following these procedures reported in several multicenter
      studies over the last decades is 0.05% to 0.32%. Currently, general consensus
      measures are available to prevent this serious complication. Abiotic biofilm
      formation with adhesion of pathogens on the surface of intraocular devices is a
      novel theory that is little understood, but widely accepted to explain the
      pathophysiologic aspects of intraocular infection. Bacterial adhesion on
      intraocular lenses has been observed in clinical practice and investigated with
      several in vitro approaches in various experimental conditions. Improvements in
      the surgical techniques used in cataract surgery and the advent of new
      antimicrobial agents with a wider spectrum of action and better penetration in
      the eye, have resulted in significant advances in the prevention and treatment of
      intraocular implant-related infection.

PMID- 19100180
TI  - [Dental implant-related infections].
AB  - Dental implant-associated infections are expected to be increasingly more common
      as the number of patients with implants for more than 10 years rises. There are 2
      stages of peri-implant infection: early mucositis, consisting of inflammation of
      the peri-implant soft tissues without loss of supporting bone, and a more
      advanced form involving a loss of osseointegration, known as peri-implantitis.
      The estimated prevalence of this latter infection is 10% of 5-year implants and
      the main risk factor is previous periodontal disease. The etiopathogenesis of
      peri-implantitis is related with reservoirs of periodontal pathogens; however
      factors that lead to colonization of the implant surface or increased
      susceptibility to infection may also have an influence. Treatment should include
      removal of the bacterial biofilm, debridement of the exposed surface, and
      surgical regeneration of the peri-implant pocket.

PMID- 19100181
TI  - [Persistent bacteremia caused by methicillin-resistant Staphylococcus aureus].

PMID- 19100182
TI  - [Pain, swelling, and progressive weakness of the left knee over 6 years].

PMID- 19100183
TI  - [Severe Rickettsia conorii infection associated with hemophagocytic syndrome].

PMID- 19100184
TI  - [Evaluation of a new immunochromatographic test for detecting adenovirus in
      respiratory samples from pediatric patients].

PMID- 19100185
TI  - [Multifocal osteoarticular infection caused by Staphylococcus aureus: when
      antibiotic resistance is not the problem].

PMID- 19100186
TI  - [Orchiepididymitis due to Mycobacterium africanum].

PMID- 19100188
TI  - [Toward modernization of the editorial process in Enfermedades Infecciosas y
      Microbiologia Clinica].

PMID- 19100189
TI  - [Controlling vertical transmission of Trypanosoma cruzi: the biggest challenge
      for imported disease in Spain].

PMID- 19100190
TI  - [Epidemiological surveillance of vertically-transmitted Chagas disease at three
      maternity hospitals in the Valencian Community].
AB  - INTRODUCTION AND AIM: Immigration to Spain of Latin Americans with Chagas disease
      in its indeterminate phase could result in vertical transmission of the disease
      or transmission by transfusion or organ transplantation. To ascertain the
      magnitude of this problem, we investigated the prevalence of bearers among women
      who gave birth in 3 state maternity hospitals in the Valencian Community and the
      incidence of vertical transmission. PATIENTS AND METHODS: An immunoprecipitation
      test to detect anti-Trypanosoma cruzi antibodies was carried out on 624 pregnant
      Latin American women. In positive cases, indirect immunofluorescence and PCR
      analysis were performed on mothers. In addition, a microhematocrit and PCR
      analysis were performed on the newborns of these mothers, and immune
      precipitation was carried out from age 7 months. Chagas-positive mothers were
      referred for outpatient care at the hospital internal medicine departments.
      Percentage of positive serology was calculated for the total number of patients
      and by country of origin. RESULTS: A total of 29 women (4.8%; 95% CI, 3.1-6.3)
      were Chagas-positive; all were asymptomatic and PCR-negative. None of their
      children were positive to the tests performed. Bolivian women were the most
      frequently affected: 24 out of 137 (17.5%; 95% CI, 11.2-23.9) DISCUSSION: The
      high prevalence of Chagas disease in the Latin American immigrant population has
      raised awareness of this disease among professionals involved in the study and
      treatment of this illness. Further epidemiological studies are needed to
      establish the feasibility of universal detection programs in this population.

PMID- 19100191
TI  - [Arthroplasty-related infection: incidence, risk factors, clinical features, and
      outcome].
AB  - INTRODUCTION: There is little information about the overall incidence, risk
      factors, and clinical management of arthroplasty-related infection in Spain.
      METHODS: The incidence of surgical site infection (SSI) in hip and knee
      arthroplasty from 2001 to 2005 was determined. Risk factors for SSI were
      investigated in 435 patients using multivariate logistic regression analysis.
      Clinical features and treatment were examined in a cohort of 58 consecutive
      patients with joint arthroplasty infection. RESULTS: The percentages of SSI in
      hip and knee arthroplasty stratified according to the National Nosocomial
      Infection Surveillance (NNIS) index were 1.86% and 1.62% (NNIS=0), 3.72% and
      2.02% (NNIS=1), and 7.20% and 6.71% (NNIS=2-3), respectively. The risk factors
      identified for developing SSI included secondary arthroplasty, duration of
      urinary catheterization, and hip arthroplasty. Fifty percent of patients with
      arthroplasty infection had type I (early) or III (hematogenous) infection. Gram
      positive cocci were the most frequent causes. Initial therapy consisted in
      debridement with preservation of the prosthesis (10 patients) or removal of the
      prosthesis (40 patients); surgery was not performed in 8 patients. After one year
      of follow up, 39 patients (67%) were considered cured, 12 (21%) had a recurrence
      or were under chronic suppressive antimicrobial therapy, and 7 (12%) had died.
      CONCLUSIONS: The incidence of SSI in our center is similar to that of other
      Spanish hospitals, but is higher than the notified incidence in the NNIS system.
      A modifiable risk factor (urinary catheterization) has been identified. Greater
      consensus for the management of these patients is desirable.

PMID- 19100192
TI  - [Antibiotic therapy in odontogenic infections in children and adolescents:
      pharmacokinetic/pharmacodynamic analysis].
AB  - INTRODUCTION: The objective of this study was to evaluate the efficacy of the
      most commonly used antimicrobial treatments in odontogenic infections in children
      and adolescents on the basis of pharmacokinetic/ pharmacodynamic (PK/PD)
      criteria. METHODS: Unbound drug plasma concentration-time curves were simulated
      with mean population pharmacokinetic parameters of amoxicillin, co-amoxiclav,
      cefuroxime axetil, spiramycin, clindamycin, azithromycin, and metronidazole. For
      drugs showing time-dependent antibacterial killing, the time above MIC90 of the
      pathogens studied was calculated (T>MIC). For drugs with concentration-dependent
      bactericidal activity, the area under the concentration-time curve (AUC)/MIC90
      ratio was calculated. RESULTS: Adequate efficacy indexes (T>MIC>40%) against all
      the microorganisms examined with the exception of Veillonella spp. were obtained
      with co-amoxiclav (80 mg/kg/day). Clindamycin (40 mg/kg/day) obtained adequate
      PK/PD indexes except for Lactobacillus, Actinobacillus actinomycetemcomitans,
      penicillin-resistant Peptostreptococcus, and Eikenella corrodens. High-dose
      amoxicillin yielded unsatisfactory results against many bacterial species.
      Azithromycin and metronidazole showed inadequate efficacy indexes against the
      majority of pathogens studied (AUC/MIC90<25). CONCLUSION: When antibiotic therapy
      is needed for odontogenic infections in children and adolescents, the most active
      empirical therapeutic choice is co-amoxiclav with high doses of amoxicillin.
      Clindamycin can be used as an alternative option. These results should be
      confirmed in clinical trials, in which the PK/PD approach could be useful for the
      design and assessment of results.

PMID- 19100193
TI  - [Chlamydophila pneumoniae: from its proteomics to arteriosclerosis].
AB  - Chlamydophila pneumoniae is a highly prevalent intracellular human pathogen with
      a unique biphasic life cycle. It is a common cause of upper respiratory infection
      and pneumonia, and is currently being studied as a potential risk factor for the
      development of atherosclerotic cardiovascular disease. The outer membrane surface
      antigens of C. pneumoniae are highly complex: some, such as the major outer
      membrane protein, are specific, but poorly immunodominant, whereas others have
      stronger immunogenicity, but are cross-reactive among Chlamydia species.
      Therefore, new, highly immunodominant, species-specific antigens should be
      sought. In this regard, the polymorphic membrane proteins (PMPs) are a) unique to
      Chlamydiae, b) often exposed on the surface of the bacteria, and c) highly
      immunogenic; these factors make them potential candidates for application in
      laboratory assays. Other chlamydial antigens, such as heat shock protein (HSP)
      60, have been associated with atherosclerotic lesions because of their ability to
      induce an immunological attack on the endothelial wall. Over the last decade,
      several studies have suggested a potential role of chronic C. pneumoniae
      infection in human atherosclerosis. Nevertheless, prospective studies with
      sufficiently large samples and a healthy comparison group, using a combination of
      direct and indirect microbiological techniques in the same subject and sample,
      are needed to establish a relationship between the infection and disease
      activity.

PMID- 19100194
TI  - [Mycological diagnosis: something is changing].
AB  - Great effort has been made in recent years to develop molecular techniques for
      laboratory diagnosis of mycosis. To this end, elucidation of the entire genomic
      sequence of the main fungal pathogens provides an unprecedented opportunity for
      clinical mycologists. There is considerable expectation regarding the potential
      application of the rapid advances in genomics and proteomics to study the
      molecular basis of fungal pathogenicity, to search for new and more effective
      antifungal drugs, and to identify fungal antigens. This article reviews the key
      aspects of fungal genomics and presents genomic and post-genomic applications of
      interest for clinical mycologists.

PMID- 19100195
TI  - [Infections associated with prosthetic heart valves, vascular prostheses, and
      cardiac pacemakers and defibrillators].
AB  - The implantation of biological or mechanical heart valves, pacemakers,
      defibrillators, and prosthetic vascular grafts can save the life of patients with
      valvular heart disease, conduction disorders, arrhythmia, or vascular disease.
      The use of these devices has increased in the general population. Antibiotic
      prophylaxis is indicated to prevent cardiovascular device-related infections,
      which are uncommon, but have high associated morbidity and mortality. We review
      the epidemiology, pathogenesis, clinical manifestations, diagnosis, treatment,
      and prevention of these infections. Staphylococci are the most common etiological
      agents, and the infection is thought to result from contamination during device
      implantation or in the early postoperative period. Positive blood culture status,
      and diagnostic imaging (transesophageal echocardiography, computed tomography,
      magnetic resonance imaging) and nuclear medicine study (scintigraphy using
      labeled leukocytes) are the basic tools to establish the diagnosis. Treatment is
      complex and requires prolonged antibiotic administration targeting the isolated
      organisms, and device removal to attain cure.

PMID- 19100196
TI  - [Skin ulcers in an immunocompromised man].

PMID- 19100197
TI  - [Increased liver enzymes and fever].

PMID- 19100198
TI  - [Urinary tract infection caused by Corynebacterium riegelii].

PMID- 19100199
TI  - [Septic arthritis due to Streptococcus dysgalactiae ssp. equisimilis].

PMID- 19100200
TI  - [From research to clinical practice: use of lopinavir/ritonavir in monotherapy].

PMID- 19100201
TI  - [Acute cerebellar ataxia complicating infectious mononucleosis].

PMID- 19100203
TI  - [Radiologia and squaring the circle].

PMID- 19100205
TI  - [Case imaging: Lemierre's syndrome with sepsis pulmonary emboli and pleural
      empyema].

PMID- 19100204
TI  - [MRI of malignant neoplasms of the uterine corpus and cervix].
AB  - OBJECTIVE: In this article, we review the role of MRI in the imaging of malignant
      neoplasms of the uterine corpus and cervix, describing its role in staging,
      treatment planning, and follow-up. CONCLUSION: MRI is not officially incorporated
      in the International Federation of Gynecology and Obstetrics (FIGO) staging
      system, but is already widely accepted as the most reliable imaging technique for
      the diagnosis, staging, treatment planning, and follow-up of both endometrial and
      cervical cancer. MRI protocols need to be optimized to obtain the best results
      and avoid pitfalls.

PMID- 19100206
TI  - [Magnetic resonance imaging and magnetic resonance spectroscopy methods for
      measuring intra- and extra-cellular pH: clinical implications].
AB  - We review the different methods for measuring pH by magnetic resonance imaging
      and magnetic resonance spectroscopy and discuss their potential diagnostic
      repercussions. We begin with a brief description of intra- and extra-cellular pH
      regulation in physiological and pathological conditions. Then we present the main
      31P or 1H magnetic resonance spectroscopy procedures, which are based on the
      dependence of the pH on the chemical displacements of the intrinsic intracellular
      inorganic phosphate or of the H2 proton of imidazole in extrinsic indicators.
      Finally, we describe the procedures that use magnetic resonance imaging, whose
      main tool is the dependence of the pH (i) on the relaxivity of certain
      paramagnetic contrast agents, or (ii) on the processes of magnetic transference
      between diamagnetic molecules (DIACEST) or paramagnetic molecules (PARACEST) and
      the free water in the tissues. We briefly illustrate the potential clinical
      applications of these new procedures.

PMID- 19100207
TI  - [The role of radiologists in the management of thyroid nodules].
AB  - We review the different techniques in the diagnostic of thyroid nodule. The
      ultrasound and, especially, sonographically guided fine-needle aspiration (US
      FNA), are the most accurate diagnostics tests to achieve a correct diagnosis of
      thyroid nodule, which is only done better by the surgery treatment and the
      pathology study of all lesion. We review the situations in which US-FNA is
      necessary and the different diagnostic and therapeutics options. Finally, we
      propose algorithms for the management of a solitary thyroid nodule, multinodular
      goiter and casually discovered nodule.

PMID- 19100208
TI  - [Case imaging: 2. Mediastinal teratoma].

PMID- 19100209
TI  - [Ultrasonographic and power Doppler appearance of locoregional metastases from
      cutaneous melanoma].
AB  - OBJECTIVE: To describe the morphological and vascular ultrasound findings of
      cutaneous melanoma locoregional metastasis, both in lymph nodes and in
      superficial soft tissues. To see if detection of these findings allows a sure
      diagnosis. MATERIALS AND METHODS: The morphological aspects of melanoma
      metastasis were evaluated with high-resolution ultrasound, and vascularisation by
      power color, by means the malignancy criteria previously described. RESULTS: 71
      loco-regional metastasis were found, in 32 patients: 15 lymph node metastases
      (21.2%) and 56 soft tissues metastases (78.8%). All of them were histologic
      confirmation. In 19 cases metastasis were not detected by clinical evaluation.
      The lymph node metastasis had: low echogenicity (100%) with heterogeneous texture
      (66.7%); absence of echogenic hilus (93.3%); a ratio between longitudinal and
      transverse diameters<2 in most cases (86.2%); and peripheral or mixed
      vascularisation (86.6%). A statistic signification (p=0.049) was proved between
      L/T ratio and vascularisation type. Soft tissues metastases presented: a maximal
      diameter between 3-27 mm (mean: 6.91); oval or round shape, sometimes lobulate;
      well-defined margins (100%); low echogenicity (100%); heterogeneous texture
      (64.3%); and they showed vascularisation even in the smallest lesions (<5 mm). A
      statistic signification (p=0.006) was proved between the size and the
      vascularisation degree. CONCLUSION: US findings allow a suspicion diagnosis of
      melanoma locoregional metastasis even when metastasis was not detected in
      physical exam.

PMID- 19100210
TI  - [Pleuropulmonary blastoma in children: imaging findings and clinical patterns].
AB  - PURPOSE: To describe the imaging findings, clinical presentation and follow up of
      pleuropulmonary blastoma (PPB) in children. MATERIALS AND METHODS: Authors
      present a retrospective review of three young children with pathologically proven
      PPB seen from 1992 to 2006 in a pediatric hospital. The imaging findings on
      simple views, CT and MRI are presented. RESULTS: The first patient showed two
      bilateral well-defined solid lung lesions on chest X-rays, with homogeneous low
      attenuation on CT. Patient is free of disease following chemotherapy and surgical
      treatment. The second patient displayed a right tension pneumothorax. After
      drainage, he presented on chest X-rays and CT an underlying multicystic lesion.
      Following chemotherapy and surgical treatment, he presented two pulmonary
      metastases, which were treated with chemotherapy and surgery. The patient is now
      free of disease. The third patient showed a complete opacification of the left
      hemithorax due to a massive pleural effusion; a pleuropulmonary solid mass was
      seen on US, CT and MRI. The disease progressed with mediastinal, orbital and
      abdominal metastasis. The patient eventually died. CONCLUSION: PPB is a rare
      chest tumor seen in young children that can present with diverse radiological
      findings, and sometimes can arise in congenital cystic lung lesions. CT is the
      gold standard technique both for diagnosis and follow-up of these tumors.

PMID- 19100211
TI  - [The role of MRI in the early diagnosis of pyomyositis in children].
AB  - OBJECTIVE: To evaluate the role of MRI in the early diagnosis and therapeutic
      assessment of pyomyositis. MATERIAL AND METHODS: We reviewed the cases of 11
      patients with proven pyomyositis presenting from January 2002 to March 2006. We
      describe the characteristic findings at plain-film radiography, ultrasound, and
      MRI, as well as the clinical presentation and laboratory findings. RESULTS: The
      mean age of presentation was 10 years (range 3-14 years); there was a male
      predominance (7 cases). Only 4 patients had predisposing conditions. The most
      common clinical symptom was fever (9 cases). The most common laboratory findings
      were elevated erythrocyte sedimentation rate (10 cases) and leukocytosis (8
      cases). Plain-film and US findings were nonspecific in all cases. Scintigraphy
      was positive in 4 cases. MRI showed osteomuscular involvement in all cases and
      enabled the abscesses to be identified. CONCLUSIONS: Pyomyositis is a primary
      bacterial infection of skeletal muscle. In recent years pyomyositis has
      increasingly been diagnosed even in patients without predisposing factors. There
      is a male predominance. Imaging is essential for the diagnosis of the
      pyomyositis, and radiologists play a crucial role in the early diagnosis of this
      infection. MRI is the imaging method of choice for characterizing the infection.

PMID- 19100212
TI  - [Case imaging: 3. Kernicterus. Magnetic resonance findings].

PMID- 19100213
TI  - [Embolization in peripheral artery bleeding with Onyx].
AB  - OBJECTIVE: This study describes use of ethylene vinyl alcohol copolymer (EVOH)
      dissolved in anhydrous dimethyl sulfoxide (DMSO) and mixed with tantalum powder
      to achieve radiopacity as an effective, safe, and manageable embolic agent in
      endovascular treatment of artery haemorrhages. MATERIALS AND METHODS: Twenty
      patients with pseudoaneurysms secondary to biopsy, or surgery were treated, 11
      musculoskeletal arteries, 9 visceral (4 gastroduodenal arteries). A diagnostic
      angiographic procedure that showed the artery lesion was always performed.
      Embolization was performed immediately, followed by post-embolization
      angiographic control. Transcatheter embolization was always performed, using a
      coaxial system consisting of a 4F hydrophilic guide catheter with 0.038"
      diameter, a microcatheter compatible with DMSO administration (Rebar
      microcatheter), and a microguide. All cases progressed with acute hemorrhagic
      syndrome of variable intensity. There were nine cases with hemorrhagic shock.
      RESULTS: All cases were satisfactorily resolved without recurrence of bleeding
      during follow-up. CONCLUSIONS: Our experience with selective embolization of
      spontaneous or traumatic artery bleeding with Onyx has been excellent due to its
      simple, rapid, and safe use.

PMID- 19100214
TI  - [Tumors of the oral cavity: the usefulness of dynamic CT].
AB  - OBJECTIVE: To demonstrate the usefulness and importance of including "puffed
      cheek" dynamic CT (PCCT) in the protocol for the diagnosis and staging of tumors
      of the oral cavity. MATERIAL AND METHODS: This is a prospective study of 62 (38
      male and 24 female) patients with epidermoid carcinoma of the oral cavity
      diagnosed and treated at our hospital during an 18-month period. The site of the
      primary tumor was the tongue (n=19), floor of the mouth (n=3), lip (n=3), gums
      (n=6), retromolar trigone (n=7), buccal mucosa (n=8), and a combination of the
      last three locations (n=16). In addition to conventional CT examination, all
      patients underwent dynamic CT of the oral cavity while maintaining their cheeks
      puffed out. RESULTS: PCCT provided additional information in 39 patients (63%),
      giving a better view of the tumor, its extension, or both. PCCT detected eight
      lesions (17%) that were not visible on the conventional CT study; these lesions
      were located in the tongue (n=3), retromolar trigone (n=1), buccal mucosa (n=3),
      and upper gum (n=1). PCCT was especially useful for evaluating lesions with
      superficial extension, in particular those in the buccal mucosa, retromolar
      trigone, and gums. PCCT provided no additional information about the tumors on
      the floor of the mouth. CONCLUSIONS: The habitual contact between the mucosal
      surfaces of the oral cavity makes some clinically obvious lesions difficult to
      identify at CT. The interposition of air acts as a natural contrast, separating
      the gums from the mucosa of the buccomaseteric region; PCCT provides relevant
      information and should be included in the imaging workup in patients with tumors
      of the oral cavity.

PMID- 19100215
TI  - [Radiological care in the Emergency Department].
AB  - In light of the abuse of imaging tests for supposed emergencies and the
      consequent negative impact of unnecessary imaging tests on the workup of true
      emergencies, on health-care costs, and on the health of the personnel
      administering the tests, this article aims to open a discussion about the
      possibility of limiting imaging tests to those strictly necessary and of
      implementing a list of indications for different imaging tests in the emergency
      department.

PMID- 19100216
TI  - [Tuberculosis of the breast: imaging findings in two patients].
AB  - Diagnosis of breast tuberculosis is difficult and rare in western countries. We
      describe two cases of mammary tuberculosis, with mastitis as clinical feature
      that fail to heal despite antibiotic therapy. Mammographic findings showed a
      large opacity involving the entire breast in case 1, and a focal asymmetric
      density with irregular margins in case 2. Sonographic findings revealed in both
      cases hypoechoic nodules with fistulous tracks and axillary lymph nodes. Magnetic
      resonance was performed in one case, which showed parenchymal asymmetry with
      heterogeneous enhancement including irregular internal ring enhancement. Fine
      needle aspiration cytology revealed inflammatory cells in first case and atypical
      cells in second case. Core needle biopsy was performed in both cases to rule out
      malignant lesions. Acid-fast bacilli were negative in both patients while
      polymerase chain reaction was positive in one case. There was a good clinical
      response to antituberculosis therapy.

PMID- 19100220
TI  - [Response to Case 2: Atlanto-axial rotational subluxation].

PMID- 19100221
TI  - [The future of radiological imaging in digestive diseases].

PMID- 19100222
TI  - [Ossified peritoneal metastasis from an osteosarcoma of the femur].

PMID- 19100224
TI  - [Quo vadis ultrasonography?].

PMID- 19100223
TI  - [Adventitial cystic disease of the popliteal artery: a case report].

PMID- 19100225
TI  - [Hepatitis B in 2008].

PMID- 19100226
TI  - [Molecular virology of the hepatitis B virus].
AB  - The hepatitis B virus (HBV) belongs to the hepadnavirus family. The genome of the
      virus, formed by a small DNA molecule with 3,200 base pairs, has 4 strongly
      overlapping protein coding regions: ORF preS/S, corresponding to the envelope
      proteins that constitute the HBV surface antigen (HBsAg); ORF preC/C, which
      encodes the viral capsid component (core antigen or HBcAg) and a non-structural
      protein that, after postranslation modification, is secreted and constitutes the
      "e" antigen (HBeAg); ORF P, which encodes the viral polymerase (polyprotein with
      DNA polymerase activity, reverse transcriptase and RNAase), and ORF X, which
      encodes a protein that acts as a multifunctional regulator for both the viral and
      cell cycles. HBV has a mutation rate of 1.4-3.2 x 105
      substitutions/nucleotide/year. As a result of this variability, the virus
      circulates as a complex mixture of genetic variants, constituting a semi-species,
      that evolves throughout the infection depending on the evolutionary pressure of
      factors such as the immune response and antiviral treatments. Based on this
      variability, HBV has been classified into 8 genotypes (A-H) defined by a
      difference of more than 8% in the sequences of the complete viral genome. This
      variability is also responsible for HBV resistance to antiviral treatments with
      nucleotide and nucleoside analogs. Diagnosis of HBV infection includes
      determination of virological markers: viral antigens (HBsAg, HBeAg), specific
      antibodies (anti-HBc, anti-HBe, anti-HBs) and study of HBV-DNA for its detection
      and quantification and determination of genotypes and viral variants.

PMID- 19100227
TI  - [Natural history and clinical manifestations of chronic hepatitis B virus].
AB  - Hepatitis B virus (HBV) infection is a serious public health problem worldwide.
      In the last few decades, major advances have been achieved that have contributed
      to greater understanding of the natural history and clinical manifestations of
      this infection. The fluctuation between viral replication and the host's immune
      response has implications in the pathogenesis and progression of the hepatic
      lesion. In immunocompetent adults, most HBV infections resolve spontaneously in
      contrast with progression to chronic infection in most infants. Patients with
      chronic hepatitis due to HBV or chronic hepatitis B can present at four phases:
      1) the immune tolerance phase, 2) HBeAg-positive chronic hepatitis B, 3) inactive
      HBsAg carrier state, and 4) HBeAg-negative chronic hepatitis. HBeAg-positive or 
      negative chronic hepatitis can progress to cirrhosis, liver failure and
      hepatocellular carcinoma. Progression to these complications is more frequent in
      HBeAg-negative forms, associated with mutations that affect the pre-core region
      and maintain active viral replication. Risk factors are HBV-DNA positive serum
      levels, an increase in serum transaminase levels and some genotypes. These
      factors highlight the need to evaluate and monitor all HBV carriers to identify
      those who could benefit from early antiviral treatment, thus avoiding progression
      to more advanced forms of liver disease. These measures could improve prevention
      and treatment of hepatitis B.

PMID- 19100228
TI  - [Interferon in hepatitis B].
AB  - Hepatitis B virus (HBV) infection is a worldwide public health problem. There are
      an estimated 350 million persons with chronic HBV infection that could progress
      to cirrhosis and hepatocarcinoma with nearly one million deaths per year. In the
      last few years the therapeutic options in chronic hepatitis B have increased and
      currently six treatments are authorized: standard interferon (IFN)-alpha,
      pegylated interferon-alpha (PEG-IFNalpha), lamivudine, adefovir, entecavir, and
      telbivudine. For the last 25 years, conventional IFNalpha has been used as the
      treatment of chronic hepatitis B (CHB) and currently PEG-IFNalpha is indicated
      due to its greater effectiveness. Both drugs are first line options for HBeAg(+)
      and HBeAg(-) CHB. The advantages of IFNalpha and PEG-IFNalpha are that these
      drugs are administered for a limited time period, they achieve a higher sustained
      response rate and do not induce HBV mutants with antiviral resistance. These
      drugs achieve greater HBeAG and HBsAG clearance due to their antiviral and
      immunomodulatory activity. PEG-IFNalpha induces sustained biochemical and
      virological response in approximately one third of patients with HBeAg(+) CHB.
      The best response to IFNalpha and PEG-IFNalpha is obtained in patients with
      elevated transaminase levels, moderate viral load and HBV genotypes A and B. The
      disadvantages of IFNalpha and PEG-IFNalpha are their adverse effects and
      contraindications. These drugs cannot be administered in patients with
      decompensated cirrhosis. The combination of nucleos(t)ide analogs with PEG
      IFNalpha could achieve much higher sustained response rates; however, which
      treatment constitutes the most suitable therapeutic strategy requires
      investigation.

PMID- 19100229
TI  - [Nucleoside and nucleotide analogs in the treatment of chronic hepatitis B].
AB  - At least 4 nucleos(t)ide analogs have been approved for the treatment of chronic
      hepatitis B: lamivudine, adefovir dipivoxil, entecavir, and telbivudine. The
      introduction of these drugs has radically changed the treatment of this disease.
      The advantages of these drugs are their oral administration, excellent
      tolerability and efficacy in all types of chronic hepatitis B (compensated and
      decompensated disease). The limitations are the need for prolonged treatments,
      which hampers adherence and can cause selection of HBV strains resistant to
      distinct drugs. The resistance rate differs for each of the drugs. Nucleotide
      analogs such as adefovir and tenofovir are useful in patients resistant to
      nucleoside analogs such as lamivudine, entecavir and telbivudine and vice versa.
      In cases of resistance to one of these drugs, combined treatment is advised.

PMID- 19100230
TI  - [Entecavir].
AB  - Chronic hepatitis B continues to be a serious problem worldwide. Because a high
      viral load is associated with greater progression to cirrhosis and
      hepatocarcinoma in these patients, new drugs that achieve rapid, potent and
      lasting suppression of viral replication must be sought. Entecavir is a new,
      highly potent antiviral agent; phase II and III studies have demonstrated this
      drug to be superior to placebo and lamivudine in patients with chronic hepatitis
      B virus in terms of histological improvement, efficacy in achieving suppression
      of viral replication and normalizing transaminase counts. The drug is well
      tolerated, since its adverse effects are usually mild or moderate and their
      incidence is similar to that found with placebo or lamivudine. Moreover, in
      treatment-naive patients, no resistance has been observed after 3 years of
      therapy. However, in patients with prior resistance to lamivudine, the incidence
      of resistance is approximately 15% at 3 years. Further studies are required that
      compare this drug with other currently available therapeutic options, as well as
      longer term trials to evaluate its safety. It seems that entecavir will occupy a
      major place in the treatment of patients with chronic hepatitis B virus
      infection.

PMID- 19100231
TI  - [Resistance in hepatitis B virus].
AB  - The development hepatitis B virus (HBV) polymerase inhibitors has revolutionised
      the treatment of chronic HBV infection. However, the emergence of resistance
      mutations can compromise their clinical efficacy and it is mandatory to know the
      mechanisms of these resistances, its clinical implications, strategies for
      prevention and how to deal with the rescue. Since HBV has a high degree of
      replication and a high error rate, during their life cycle it will produce a
      large number of punctual mutations in individuals with active replication. Due to
      the large size of the HBV genome, all the possible changes may occur daily and
      should be screened before starting any antiviral therapy. Therefore, in
      individuals infected with HBV there is a mixture of similar viruses that evolves
      over time (quasispecies), some of which are carriers of resistance mutations to
      antivirals, which explains why they can be selected quickly after exposure to
      drug. Of the five drugs approved in Europe for the treatment of hepatitis B,
      three of them (lamivudine, adefovir and entecavir) are likely to be affected
      directly by these mutations, as well as other active drugs, such as telbivudine,
      tenofovir and the emtricitabine. The characterization of the resistance mutations
      is helpful for the prevention and the optimization of antiviral therapies.

PMID- 19100232
TI  - [Clinical management of patients with chronic hepatitis B virus infection].
AB  - Chronic hepatitis B is still a major public health problem, aggravated by the
      growing phenomenon of immigration from areas with a high prevalence of infection
      with this virus. In the last few years, marked progress has been achieved in
      diagnostic methods, knowledge of the natural history of the disease and in
      therapeutic options, including liver transplantation, which has improved survival
      in these patients. These advances have been accompanied by an increase in the
      complexity of decision making. Six treatments have currently been approved for
      hepatitis B, including two interferon formulations--standard and pegylated--and
      four neucleos(t)ide analogs, lamivudine, adefovir, entecavir and telbivudine, as
      well as two further drugs that are used in patients coinfected with HIV,
      tenofovir and emtricitabine. However, none of the current treatments is able to
      eradicate the virus and consequently prolonged treatments are often required with
      the consequent risk of generating resistance. For this reason, as well as the
      heterogeneity of the natural history of the disease, there is a lack of consensus
      on the indications for treatment and the parameters in which treatment should be
      based, the most suitable drug or drug combination, and the criteria to be used to
      continue, modify or suspend treatment. Therefore, despite the enormous progress
      made, numerous questions remain that make the clinical management of these
      patients a major challenge.

PMID- 19100233
TI  - [Hepatitis B in pregnant women and children].
AB  - In pregnant women and children, the hepatitis B virus can cause acute or chronic
      hepatitis or liver cirrhosis. Perinatally-acquired infection causes persistent
      infection in 90% of cases and can be avoided through administration of the
      hepatitis B vaccine and specific immunoglobulin in the first day of life.
      Prevention of mother-to-child transmission requires screening for hepatitis B
      surface antigen (HBsAg) in pregnant women to identify which newborns should be
      immunized. In some countries this strategy is substituted by universal
      vaccination of neonates. In infected children, inactivation of viral replication
      with conversion of HBeAG-positive to anti-HBe-positive status usually occurs. If
      this seroconversion does not take place and necroinflammatory activity persists
      in the liver, the use of antiviral agents such as interferon or nucleoside and
      nucleotide analogs is warranted.

PMID- 19100234
TI  - [Hepatitis B in patients with HIV infection].
AB  - Chronic hepatitis B virus infection affects approximately 10% of HIV-infected
      patients. There are an estimated 4 million patients with HIV/HBV coinfection. HIV
      infection has a deleterious effect on the natural history of chronic hepatitis B
      and increases the risk of progression to cirrhosis and terminal liver disease.
      Since the widespread use of highly active antiviral therapy (HAART), liver
      disease has emerged as one of the main causes of morbidity and mortality in HIV
      positive patients. Therefore, all patients with HIV/HBV coinfection should be
      evaluated for treatment of hepatitis B, independently of the CD4 lymphocyte
      count. Six drugs are currently authorized for the treatment of chronic hepatitis
      B: standard interferon-alpha (2a and 2b), pegylated interferon alpha-2a,
      lamivudine, adefovir, entecavir and telbivudine. Other drugs with activity
      against HBV, such as tenofovir and emtricitabine, are used for the treatment of
      HIV infection. In patients not requiring HAART, treatment of hepatitis B should
      preferably consist of drugs without activity against HIV, such as pegylated
      interferon or adefovir. In contrast, in patients requiring HAART, a combination
      of drugs with activity against both viruses should be used, such as lamivudine,
      emtricitabine and tenofovir, with the aim of achieving maximal viral suppression
      and avoiding the development of resistance. Patients with HIV/HBV coinfection
      require periodic clinical and virological monitoring. Patients with cirrhosis
      should undergo ultrasonography and alphafetoprotein determination every 6 months
      for the early detection of hepatocellular carcinoma.

PMID- 19100235
TI  - Solid-phase nano-extraction and laser-excited time-resolved Shpol'skii
      spectroscopy for the analysis of polycyclic aromatic hydrocarbons in drinking
      water samples.
AB  - A unique method for screening polycyclic aromatic hydrocarbons in drinking water
      samples is reported. Water samples (500 microl) are mixed and centrifuged with
      950 microl of a commercial solution of 20 nm gold nanoparticles for pollutants
      extraction. The precipitate is treated with 2 microl of 1-pentanethiol and 48
      microl of n-octane, and the supernatant is then analyzed via laser-excited time
      resolved Shpol'skii spectroscopy. Fifteen priority pollutants are directly
      determined at liquid helium temperature (4.2 K) with the aid of a cryogenic fiber
      optic probe. Unambiguous pollutant determination is carried out via spectral and
      lifetime analysis. Limits of detection are at the parts-per-trillion level.
      Analytical recoveries are similar to those obtained via high-performance liquid
      chromatography. The simplicity of the experimental procedure, use of microliters
      of organic solvent, short analysis time, selectivity, and excellent analytical
      figures of merit demonstrate the advantages of this environmentally friendly
      approach for routine analysis of numerous samples.

PMID- 19100236
TI  - Fluctuating partially native-like topologies in the acid denatured ensemble of
      autolysis resistant HIV-1 protease.
AB  - Folding, in-vivo, starts from a denatured state and thus the nature of the
      denatured state would play an important role in directing the folding of a
      protein. We report here NMR characterization of the acid-denatured state of a
      mutant of HIV-1 protease, designed to prevent autolysis (Q7K, L33I, L63I) and to
      prevent cysteine oxidation (C67A and C95A). Secondary chemical shifts, TALOS
      analysis of chemical shifts and (15)N relaxation data (R(1), R(2), NOE) coupled
      with AABUF and hydrophobicity calculations, suggest formation of hydrophobic
      clusters and possibility of some partially native-like topologies in the acid
      denatured state of the protease. The structural and dynamics characteristics of
      the acid denatured PR seem to be considerably different from those of the
      guanidine or urea denatured states of some variants of PR. These would have
      implications for the folding and auto-processing of the enzyme in-vivo.

PMID- 19100238
TI  - Induction of STAP-1 promotes neurotoxic activation of microglia.
AB  - Activated microglia contribute to neurodegenerative processes in the brain and
      the retina. Via DNA-microarray analysis, we have previously identified up
      regulation of several immune-related genes in the dystrophic retina of
      retinoschisin-deficient (Rs1h(-/Y)) mice. Here we report a strong overexpression
      of transcripts for the signal-transducing adaptor protein-1 (STAP-1) in isolated
      Rs1h(-/Y) microglia. Furthermore, STAP-1 expression was induced in activated bone
      marrow-derived macrophages as well as LPS-, interferon-gamma-, and CpG-stimulated
      myeloid cell lines. Ectopic expression of STAP-1 in BV-2 microglia changed the
      morphology and cytoskeletal organization of the cells and transformed ramified
      cells to an activated state. STAP-1 overexpression also leads to an interaction
      with the M-CSF receptor/c-Fms diminishing its ligand-dependent phosphorylation.
      Finally, STAP-1 expressing cells showed strongly reduced migration with increased
      cytotoxicity against 661W photoreceptor like cells. Taken together, our study
      implicates a previously unknown role of STAP-1 in pro-inflammatory microglia
      activation potentially contributing to neuronal apoptosis and degeneration.

PMID- 19100237
TI  - Nitric oxide and airway epithelial barrier function: regulation of tight junction
      proteins and epithelial permeability.
AB  - Acute airway inflammation is associated with enhanced production of nitric oxide
      (NO(.)) and altered airway epithelial barrier function, suggesting a role of
      NO(.) or its metabolites in epithelial permeability. While high concentrations of
      S-nitrosothiols disrupted transepithelial resistance (TER) and increased
      permeability in 16HBE14o- cells, no significant barrier disruption was observed
      by NONOates, in spite of altered distribution and expression of some TJ proteins.
      Barrier disruption of mouse tracheal epithelial (MTE) cell monolayers in response
      to inflammatory cytokines was independent of NOS2, based on similar effects in
      MTE cells from NOS2-/- mice and a lack of effect of the NOS2-inhibitor 1400W.
      Cell pre-incubation with LPS protected MTE cells from TER loss and increased
      permeability by H2O2, which was independent of NOS2. However, NOS2 was found to
      contribute to epithelial wound repair and TER recovery after mechanical injury.
      Overall, our results demonstrate that epithelial NOS2 is not responsible for
      epithelial barrier dysfunction during inflammation, but may contribute to
      restoration of epithelial integrity.

PMID- 19100239
TI  - The direct excitatory effect of IL-1beta on cerebellar Purkinje cell.
AB  - Interleukin (IL)-1beta is one of the important proinflammatory cytokines in
      neural as well as immune systems, and plays a pivotal role in the
      neuroinflammation. We previously demonstrated that cerebellar IL-1beta is
      involved in kainate-induced ataxia, i.e., IL-1beta was activated in the
      cerebellum with systemic administration of kainate, and its type I receptor (IL
      1R) was expressed at a soma of cerebellar Purkinje cells. In this study, we
      examined the effect of IL-1beta on cerebellar Purkinje cell function by recording
      extracellular neuronal activities in anesthetized mice. Systemic administration
      of kainate increased the firing rates of cerebellar Purkinje cells in normal mice
      but showed little effect in IL-1R-knockout (IL-1R-KO) mice. Moreover,
      microiontophoretic administration of IL-1beta to cerebellar Purkinje cells
      increased the firing rates promptly in response to IL-1beta. The present results
      demonstrate that IL-1 system exerts a direct modulatory effect on cerebellar
      Purkinje cells.

PMID- 19100240
TI  - Epigenetic inactivation of SLIT2 in human hepatocellular carcinomas.
AB  - Recent findings have shown that SLIT2 appears to function as a novel tumor
      suppressor gene. In addition, hypermethylation of its promoter region has been
      detected in various cancers, including breast and lung cancer, colorectal
      carcinoma, and gliomas. Here, we report for the first time that there is
      epigenetic silencing of SLIT2 in human hepatocellular carcinoma (HCC).
      Downregulation of SLIT2 was detected in 6 of 8 (75%) HCC cell lines by
      quantitative real-time RT-PCR (qRT-PCR), and the downregulation of SLIT2 was
      generally dependent on the degree of methylation at the promoter region.
      Furthermore, expression of SLIT2 was restored in relatively low-expressing cell
      lines after treatment with 5-aza-2-deoxycytidine (5-Aza-dC). Downregulation of
      SLIT2 expression was also detected in 45 of 54 primary HCC samples (83.3%), and
      the decrease in expression was significantly correlated with CpG island
      hypermethylation. This decrease of SLIT2 expression was also associated with
      lymph node metastasis in HCC. Moreover, overexpression of SLIT2 in SMMC-7721
      cells induced by recombinant adenovirus suppressed cell growth, migration, and
      invasion, These results suggest that epigenetic inactivation of SLIT2 in HCC may
      be important in the development and progression of HCC. Thus, SLIT2 may be useful
      as a therapeutic target in the treatment of HCC.

PMID- 19100241
TI  - AHR-mediated immunomodulation: the role of altered gene transcription.
AB  - The immune system is a sensitive target for aryl hydrocarbon receptor (AHR)
      mediated transcriptional regulation. Most of the cells that participate in immune
      responses express AHR protein, and many genes involved in their responses contain
      multiple DRE sequences in their promoters. However, the potential involvement of
      many of these candidate genes in AHR-mediated immunomodulation has never been
      investigated. Many obstacles to understanding the transcriptional effects of AHR
      activation exist, owing to the complexities of pathogen-driven inflammatory and
      adaptive immune responses, and to the fact that activation of AHR often
      influences the expression of genes that are already being regulated by other
      transcriptional events in responding cells. Studies with TCDD as the most potent,
      non-metabolized AHR ligand indicate that AHR activation alters many inflammatory
      signals that shape the adaptive immune response, contributing to altered
      differentiation of antigen-specific CD4(+) T helper (TH) cells and altered
      adaptive immune responses. With TCDD, most adaptive immune responses are highly
      suppressed, which has been recently linked to the AHR-dependent induction of
      CD4(+)CD25(+) regulatory T cells. However activation of AHR by certain non-TCDD
      ligands may result in other immune outcomes, as a result of metabolism of the
      ligand to active metabolites or to unknown ligand-specific effects on AHR
      mediated gene transcription. Based on studies using AHR(-/-) mice, evidence for a
      role of endogenous AHR ligands in regulation of the immune response is growing,
      with bilirubin and lipoxinA4 representing two promising candidates.

PMID- 19100243
TI  - The alkyl chain length of 3-alkyl-3',4',5,7-tetrahydroxyflavones modulates
      effective inhibition of oxidative damage in biological systems: illustration with
      LDL, red blood cells and human skin keratinocytes.
AB  - It is shown that the relationship between the alkyl chain length of 3-alkyl
      3',4',5,7 tetrahydroxyflavones (FnH) bearing alkyl chains of n=1, 4, 6, 10
      carbons and their capacity to counter oxidative damage varies markedly with the
      nature of the biological system. In Cu(2+)-induced lipid peroxidation of low
      density lipoprotein (LDL), the less hydrophobic short-chain F1H and F4H are
      probably located in the outer layer of LDL and parallel the reference flavonoid
      antioxidant, quercetin (Q) as effective inhibitors of lipid peroxidation. A
      marked inhibition of haemolysis induced in red blood cells (RBC) suspensions by
      the membrane-permeant oxidant, tert-butylhydroperoxide (t-BuOOH), is observed
      with F4H and F6H present at concentration in the micromolar range. However, F10H
      the most hydrophobic FnH is even more effective than Q against both haemolysis
      and lipid peroxidation as measured by malondialdehyde (MDA) equivalents. In
      oxidation of RBC by H(2)O(2,) at least 50 times more F6H and F10H than by t-BuOOH
      are required to only partly inhibit haemolysis and MDA production. The F1H, F4H
      and Q are found rather inactive under these conditions. At concentrations in the
      micromolar range, a marked protection against the cytotoxic effects of the t
      BuOOH-induced oxidative stress in human skin NCTC 2544 keratinocytes is also
      exhibited by the four FnH antioxidants and is comparable to that of Q. Thus, the
      four FnH species under study may be considered as potent antioxidants which
      manifest complementary anti-oxidative actions in biological systems of markedly
      different complexity.

PMID- 19100244
TI  - The ERP signature of sound rise time changes.
AB  - Sounds, whether speech or non-speech, vary in how rapidly their peak amplitudes
      are reached. The time taken for sounds to reach their maximum amplitude is known
      as the rise time and this variable is an important perceptual cue for
      representation of the sound amplitude envelope. In the experiments described here
      healthy adult volunteers passively listened to tones varying in rise time. An
      oddball design was used and both N1 and MMN components were examined. Experiment
      1 contrasted tone stimuli of 15 ms vs. 185 ms rise time. The shorter 15 ms rise
      time stimuli elicited an N1b over central frontal electrodes of significantly
      greater amplitude than the 185 ms rise time stimuli. MMN was also observable for
      both the 15 ms and 185 ms rise time tones when the same stimuli served as deviant
      vs. standard. Experiment 2 explored the possible confound of rise time and
      overall stimulus intensity change (tones with shorter rise times sound louder).
      New stimuli were created in which overall stimulus intensity between short and
      long rise times was perceptually matched. N1b amplitude differences to the
      contrastive rise times were still observed, suggesting that N1b may reflect an
      auditory cortex detector mechanism sensitive to changes in rise time, relatively
      independently of sound intensity changes. These findings are discussed with
      reference to their implications for speech perception processes.

PMID- 19100242
TI  - Activation of the aryl hydrocarbon receptor by TCDD inhibits senescence: a tumor
      promoting event?
AB  - Activation of the aryl hydrocarbon receptor (AHR) by the agonist, 2,3,7,8
      tetrachlorodibenzo-p-dioxin (TCDD) has been shown to promote tumor formation in
      both liver and skin. In the liver, but not the skin, the AHR-mediated events that
      contribute to TCDD's tumor promoting activities have been studied in some detail
      and are thought to involve perturbation of cell fate processes. However, studies
      performed using cultured cells have often resulted in apparent contradictory
      results indicating that the impact of TCDD on cell fate processes may be cell
      context dependent. We and others have shown that in primary cultured
      keratinocytes TCDD increases post-confluent proliferation and increases late
      differentiation. Further, our studies performed in these cells indicate that TCDD
      can also inhibit culture-induced senescence. While senescence, a permanent cell
      cycle arrest, is emerging as an important process regulated by oncogenes and
      considered to be of therapeutic importance, its role with respect to TCDD/AHR
      mediated tumor promotion has not been fully considered. The intent of this
      article is to focus primarily on senescence as a cell process relevant to skin
      tumorigenesis and explore the idea that the inhibition of senescence by TCDD
      could be an important mechanism by which it may exert its tumor promoting effects
      in the skin.

PMID- 19100245
TI  - Intra-hippocampal administration of the VEGF receptor blocker PTK787/ZK222584
      impairs long-term memory.
AB  - A number of studies have established a role for vascular endothelial growth
      factor (VEGF) in angiogenesis. Recent reports have shown that VEGF overexpression
      in the hippocampus improves learning and memory and is associated with enhanced
      neurogenesis. PTK787/ZK222584 (PTK/ZK) is a reported inhibitor of VEGFR signaling
      that is currently being tested for its effects on lung and colon cancer. However,
      the influence of this drug on cognition has not been examined. In the present
      study, we questioned if post-training administration of PTK/ZK influences
      hippocampus-dependent memory. When administered to rats immediately following
      massed training in the Morris water maze, PTK/ZK impaired spatial memory
      retention tested 48 h later. This impairment was evidenced by increased latency
      to the hidden platform and fewer platform crossings. However, this impairment was
      not associated with a change in neurogenesis during this time frame. PTK/ZK
      infusion did not reduce VEGFR or AKT phosphorylation, but increased the
      phosphorylation of ERK. These studies suggest that VEGFR inhibitors such as
      PTK/ZK may negatively influence cognition.

PMID- 19100246
TI  - Interaction of Na2B12H11SH with dimyristoyl phosphatidylcholine liposomes.
AB  - Previous investigations have revealed that the boron cluster compound Na2B12H11SH
      (BSH) is very potent in causing major structural rearrangements of and leakage
      from phosphatidylcholine liposomes. This somewhat unexpected finding is
      interesting from a fundamental point of view and may also constitute the basis of
      future important pharmaceutical/medical applications of BSH. In order to further
      explore the BSH-lipid interaction, we have studied the effects caused by BSH on
      dimyristoyl phosphatidylcholine (DMPC) liposomes. Cryo-transmission electron
      microscopy showed that BSH induces aggregation, membrane rupture and increasing
      wall thickness of the liposomes. Differential scanning calorimetry revealed a BSH
      dependent shift of the gel to liquid crystalline phase transition temperature of
      DMPC. The zeta potential of the liposomes decreases with increasing BSH
      concentrations, and an apparent dissociation constant of 0.23 mM was found. BSH
      caused leakage of liposome-encapsulated carboxyfluorescein; leakage was higher at
      23 degrees C (near the phase transition temperature) than at 15 degrees C and 37
      degrees C. It induced lipid mixing only at very high concentrations.

PMID- 19100247
TI  - Plasma lysosomal enzyme activities in congenital disorders of glycosylation,
      galactosemia and fructosemia.
AB  - BACKGROUND: Variable increases in the plasma activity of different lysosomal
      enzymes have been reported in patients with congenital disorders of glycosylation
      (CDG). In particular, elevated plasma aspartylglucosaminidase activity (AGA) has
      been found in the majority of CDG type I patients. We report on the plasma
      activity of AGA and other lysosomal enzymes in patients with different types of
      primary and secondary CDG defects. METHODS: AGA, alpha-mannosidase, beta
      mannosidase and beta-hexosaminidase activities were assayed in the plasma of
      patients with CDGI (4CDGIa, 4CDGIx) and CDGIIx (5, all with a combined N- and O
      glycosylation defect), classical galactosemia (GALT) (n=3) and hereditary
      fructose intolerance (HFI) (n=2). RESULTS: Increased AGA and beta-hexosaminidase
      activities were found in all and 7/8 of the GDGI patients respectively. All
      enzymic activities were normal in the CDGIIx patients. Elevated AGA and beta
      hexosaminidase activity was also seen in GALT and HFI patients before treatment,
      when transferrin isoelectric focusing (TfIEF) patterns were also abnormal.
      CONCLUSIONS: Increased AGA plasma activity, although a consistent finding in CDGI
      patients, is not specific to this group of disorders since it is also observed in
      untreated cases of GALT and HFI. Furthermore, plasma AGA activity cannot serve as
      a marker for CDGII disorders. In conjunction with TfIEF it could be used in the
      follow up of GALT and HFI patients.

PMID- 19100248
TI  - Cyclosporine concentration-dependent increase in concentration ratio of
      mycophenolic acid acyl and phenol glucuronides to mycophenolic acid in stable
      kidney transplant recipients.
AB  - OBJECTIVES: The aim of this study was to evaluate the influence of cyclosporine
      (CyA) and tacrolimus (Tac) on the pharmacokinetics of mycophenolic acid (MPA) and
      its glucuronides. DESIGN AND METHODS: Kidney transplant recipients treated with
      mycophenolate mofetil and CyA (n=18) or Tac (n=17) in the stable phase were
      enrolled. The dependence of the trough concentration (C(0)) ratios of MPA acyl
      glucuronide (AcMPAG) to MPA (AcMPAG/MPA) and MPA phenol glucuronide (MPAG) to MPA
      (MPAG/MPA) on CyA C(0) or Tac C(0) was evaluated. RESULTS: AcMPAG C(0) and MPAG
      C(0) were significantly higher in CyA- than Tac-treated recipients (P=0.04 and
      0.02, respectively). AcMPAG/MPA and MPAG/MPA were significantly correlated to CyA
      C(0) (r=0.75, P<0.01 and r=0.81, P<0.01, respectively), but not to Tac C(0).
      CONCLUSIONS: CyA increased AcMPAG/MPA as well as MPAG/MPA in a concentration
      dependent manner, suggesting that higher CyA may cause AcMPAG-related adverse
      reactions. Tac did not alter pharmacokinetics of MPA and its glucuronides.

PMID- 19100249
TI  - Evaluation of apolipoprotein M as a biomarker of coronary artery disease.
AB  - OBJECTIVE: To investigate the possible role of apolipoprotein M (ApoM) in the
      development of coronary artery disease (CAD). DESIGN AND METHODS: Case-controlled
      study, which consisted of 118 CAD patients and 255 unrelated subjects used as
      control group. Plasma concentration of ApoM was determined by dot blot, severity
      of CAD was expressed with Gensini score or the numbers of lesioned coronary
      arteries, and serum lipid levels were also measured. RESULTS AND DISCUSSION: Our
      study shows the mean level of plasma ApoM is 1.3757+/-0.1493 ODu mm(-2) in CAD
      patients, while it is 1.3502+/-0.1288 ODu mm(-2) in control group, and there are
      significant differences in plasma level of ApoM between two groups (t=0.032,
      P<0.05). Concentration of plasma ApoM is positively associated with plasma total
      cholesterol (r=0.38, P=0.025), high density lipoprotein cholesterol (r=0.29,
      P=0.03), low density lipoprotein cholesterol (r=0.16, P=0.03) and apolipoproein A
      I (r=0.24, P=0.03). Multiple logistic and linear regression analysis showed that
      plasma concentration of ApoM did not correlate either with the number of lesioned
      coronaries or the Gensini score after adjusted for conventional cardiovascular
      risk factors (P>0.05, respectively). CONCLUSION: The findings suggest that ApoM
      could not be an independent risk factor but a biomarker of CAD.

PMID- 19100250
TI  - Delineating metamorphic pathways in the ascidian Ciona intestinalis.
AB  - In most ascidians, metamorphosis of tadpole-like swimming larvae is accompanied
      by dynamic changes in their shape to form sessile adults. The mechanisms
      underlying ascidian metamorphosis have been debated for a long time. Although
      recent molecular studies have revealed the presence of various molecules
      involving in this process, the basic mechanism of the metamorphic events is still
      unclear. For example, it has not been solved whether all metamorphic events are
      organized by the same single pathway or by multiple, independent pathways. In the
      present study, we approached this question using the ascidian Ciona intestinalis.
      When the papillae and preoral lobes of the larvae were cut off, the papillae-cut
      larvae initiated certain trunk metamorphic events such as the formation of an
      ampulla, body axis rotation and adult organ growth without other metamorphic
      events. This observation indicates that metamorphic events can be divided into at
      least two groups, events initiated in the papillae-cut larva and events not
      initiated in this larva. In addition to this observation, we have isolated a
      novel mutant, tail regression failed (trf), which shows similar phenotypes to
      those of papillae-cut larvae. The phenotypes of trf mutants are basically
      different from those of swimming juvenile mutants (Sasakura, Y., Nakashima, K.,
      Awazu, S., Matsuoka, T., Nakayama, A., Azuma, J., Satoh, N., 2005. Transposon
      mediated insertional mutagenesis revealed the functions of animal cellulose
      synthase in the ascidian Ciona intestinalis. Proc. Natl. Acad. Sci. U. S. A. 102,
      15134-15139.), which also show abnormal metamorphosis. These findings suggest a
      model by which ascidian metamorphic events can be classified into four groups
      initiated by different pathways.

PMID- 19100251
TI  - Activation of Pax3 target genes is necessary but not sufficient for neurogenesis
      in the ophthalmic trigeminal placode.
AB  - Vertebrate cranial neurogenic placodes are relatively simple model systems for
      investigating the control of sensory neurogenesis. The ophthalmic trigeminal
      (opV) placode, for which the earliest specific marker is the paired domain
      homeodomain transcription factor Pax3, forms cutaneous sensory neurons in the
      ophthalmic lobe of the trigeminal ganglion. We previously showed that Pax3
      expression in avian opV placode cells correlates with specification and
      commitment to a Pax3+, cutaneous sensory neuron fate. Pax3 can act as a
      transcriptional activator or repressor, depending on the cellular context. We
      show using mouse Splotch(2H) mutants that Pax3 is necessary for the normal
      neuronal differentiation of opV placode cells. Using an electroporation construct
      encoding a Pax3-Engrailed fusion protein, which represses Pax3 target genes, we
      show that activation of Pax3 target genes is required cell-autonomously within
      chick opV placode cells for expression of the opV placode markers FGFR4 and Ngn2,
      maintenance of the preplacodal marker Eya2, expression of Pax3 itself (suggesting
      that Pax3 autoregulates), neuronal differentiation and delamination. Mis
      expression of Pax3 in head ectoderm is sufficient to induce FGFR4 and Ngn2
      expression, but neurons do not differentiate, suggesting that additional signals
      are necessary to enable Pax3+ cells to differentiate as neurons. Mis-expression
      of Pax3 in the Pax2+ otic and epibranchial placodes also downregulates Pax2 and
      disrupts otic vesicle closure, suggesting that Pax3 is sufficient to alter the
      identity of these cells. Overall, our results suggest that activation of Pax3
      target genes is necessary but not sufficient for neurogenesis in the opV placode.

PMID- 19100252
TI  - Sfrp1 and Sfrp2 are required for normal male sexual development in mice.
AB  - Secreted frizzled-related proteins (Sfrps) are antagonists of WNT signalling
      implicated in a variety of biological processes. However, there are no reports of
      a direct role for Sfrps in embryonic organogenesis in mammals. Using in vivo loss
      of-function studies we report here for the first time a redundant role for Sfrp1
      and Sfrp2 in embryonic sexual development of the mouse. At 16.5 dpc, male embryos
      lacking both genes exhibit multiple defects in gonad morphology, reproductive
      tract maturation and gonad positioning. Abnormal positioning of the testis
      appears to be due to failed gubernaculum development and an unusually close
      association between the cranial end of the reproductive tract and the kidney. The
      testes of double homozygotes are smaller than controls, contain fewer cords from
      the earliest stages, but still express Insl3, which encodes the hormone required
      for gubernacular masculinisation. Lgr8, which encodes the Insl3 receptor, is also
      expressed in the mutant gubernaculum, suggesting that Sfrp1/Sfrp2 signalling is
      not required for expression of the ligand or receptor that controls
      transabdominal testicular descent. Similarities between the abnormalities of
      embryonic sexual development in Sfrp1(-/-)Sfrp2(-/-) embryos with those exhibited
      by the Looptail and Wnt5a mutants suggest that disrupted non-canonical Wnt
      signalling may cause these defects.

PMID- 19100253
TI  - Mitf functions as an in ovo regulator for cell differentiation and proliferation
      during development of the chick RPE.
AB  - Mitf has been reported to play a crucial role in regulating the differentiation
      of pigment cells in homeothermal animals, i.e. the melanocytes and the retinal
      pigment epithelium (RPE). However, less is known about the functions of Mitf in
      the developing RPE. To elucidate such functions, we introduced wild-type and
      dominant-negative Mitf expression vectors into chick optic vesicles by
      electroporation. Over-expression of wild-type Mitf altered neural retina cells to
      become RPE-like and repressed the expression of neural retina markers in vivo. In
      contrast, dominant-negative Mitf inhibited pigmentation in the RPE. The
      percentage of BrdU-positive cells decreased during normal RPE development, which
      was followed by Mitf protein expression. The percentage of BrdU-positive cells
      decreased in the wild-type Mitf-transfected neural retina, but increased in the
      dominant-negative Mitf-transfected RPE. p27(kip1), one of the cyclin-dependent
      kinase inhibitors, begins to be expressed in the proximal region of the RPE at
      stage 16. Transfection of wild-type Mitf induced expression of p27(kip1), while
      transfection of dominant-negative Mitf inhibited p27(kip1) expression. We found
      that Mitf was associated with the endogenous p27(kip1) 5' flanking region. These
      results demonstrate for the first time "in vivo" that Mitf uniquely regulates
      both differentiation and cell proliferation in the developing RPE.

PMID- 19100254
TI  - Sequential RARbeta and alpha signalling in vivo can induce adult forebrain neural
      progenitor cells to differentiate into neurons through Shh and FGF signalling
      pathways.
AB  - We show here the role of retinoic acid receptor (RAR) beta and alpha signalling
      in proliferation and differentiation of endogenous adult forebrain neural
      progenitor cells (NPCs). RARbeta activation stimulates Sonic hedgehog signalling
      (Shh), and induces the proliferation of the NPCs. They can be induced to become
      Doublecortin (DCX) expressing migrating neuroblasts by RARalpha signalling, some
      of which differentiate into cholinergic neurons. The same signalling pathways
      cause the proliferation of embryonic forebrain NPCs. These cells express glial
      fibrillary acidic protein (GFAP) and are predominantly uni/bipolar, two
      characteristics of neuronal progenitor cells. We further show that fibroblast
      growth factor (FGF) signalling, induces the expression of the retinoic acid
      degrading enzyme cytochrome P450 (cyp) 26a1, and that one of its products, 4-oxo
      RA, mimics the action of the RARalpha agonist in the differentiation of the NPCs
      into cholinergic neurons.

PMID- 19100255
TI  - C. elegans RNA-binding proteins PUF-8 and MEX-3 function redundantly to promote
      germline stem cell mitosis.
AB  - Maintenance of mitotically cycling germline stem cells (GSCs) is vital for
      continuous production of gametes. In worms and insects, signaling from
      surrounding somatic cells play an essential role in the maintenance of GSCs by
      preventing premature differentiation. In addition, germ cell proteins such as the
      Drosophila Pumilio and Caenorhabditis elegans FBF, both members of the PUF family
      translational regulators, contribute to GSC maintenance. FBF functions by
      suppressing GLD-1, which promotes meiotic entry. However, factors that directly
      promote GSC proliferation, rather than prevent differentiation, are not known.
      Here we show that PUF-8, another C. elegans member of the PUF family and MEX-3, a
      KH domain translational regulator, function redundantly to promote GSC mitosis.
      We find that PUF-8 protein is highly enriched in mitotic germ cells, which is
      similar to the expression pattern of MEX-3 described earlier. The puf-8(-) mex-3(
      ) double mutant gonads contain far fewer germ cells than both single mutants and
      wild-type. While these cells lack mitotic, meiotic and sperm markers, they retain
      the germ cell-specific P granules, and are capable of gametogenesis if GLP-1,
      which normally blocks meiotic entry, is removed. Significantly, we find that at
      least one of these two proteins is essential for germ cell proliferation even in
      meiotic entry-defective mutants, which otherwise produce germ cell tumors. We
      conclude PUF-8 and MEX-3 contribute to GSC maintenance by promoting mitotic
      proliferation rather than by blocking meiotic entry.

PMID- 19100256
TI  - Identification of a novel 5-HT(4) receptor splice variant (r5-HT(4c1)) and
      preliminary characterisation of specific 5-HT(4a) and 5-HT(4b) receptor
      antibodies.
AB  - The human 5-hydroxytryptamine (5-HT(4)) receptor is encoded by a highly complex
      gene which gives rise to at least 10 distinct splice variants. However, the
      functional relevance of these variants is unknown. In rat, only three such
      variants have been identified, 5-HT(4a) (r5-HT(4a)), 5-HT(4b) (r5-HT(4b)) and 5
      HT(4e) (r5-HT(4e)). In the current study we identify and characterise the
      pharmacology of a novel rat splice variant (r5-HT(4c1)) and present the first
      comprehensive analysis of 5-HT(4) splice variant mRNA expression levels
      throughout the rat gastrointestinal tract. In addition, we describe preliminary
      characterisation of the first 5-HT(4) splice variant specific antibodies. In
      transfected cells, r5-HT(4c1) receptor exhibited similar binding properties to r5
      HT(4a) and r5-HT(4b). Functional studies showed that 5-HT(4) agonists
      prucalopride (4-amino-5-chloro-2,3-dihydro-N-[1-(3-methoxypropyl)-4-piperidinyl]
      7-benzofuran carboxamide monohydrochloride and renzapride (+/-)-endo-4-amino-5
      chloro-2-methoxy-N-(1-azabicyclo[3.3.1]non-4-yl)benzamide monohydrochloride)
      acted as partial agonists at r5-HT(4c1), but full agonists at r5-HT(4a) and r5
      HT(4b). Moreover, in contrast to r5-HT(4a) and r5-HT(4b), r5-HT(4c1) was not
      constitutively active. TaqMan mRNA analysis showed that r5-HT(4a) expression in
      brain and dorsal root ganglion exceeded that in the gastrointestinal tract,
      whilst the reverse was true for r5-HT(4b) and r5-HT(4c1). mRNA expression of each
      variant also increased distally throughout the gastrointestinal tract with the
      highest levels in the colon. r5-HT(4a) and r5-HT(4b) specific immunoreactivity
      was abundant on enteric neurons in jejunum, ileum and colon as well as neurons
      and satellite cells of the dorsal root ganglion. Only r5-HT(4b) immunoreactivity
      was observed on endocrine cells in the duodenum. These data could have
      implications in rat models and aid understanding of 5-HT(4) splice variant
      function.

PMID- 19100257
TI  - A single subcutaneous injection of ozone prevents allodynia and decreases the
      over-expression of pro-inflammatory caspases in the orbito-frontal cortex of
      neuropathic mice.
AB  - The neuropathic pain model consisting of the spared nerve injury of the sciatic
      nerve was used in the mouse to examine whether peripheral neuropathy is capable
      of generating over-expression of pro-inflammatory and pro-apoptotic genes in the
      orbito-frontal cortex, together with allodynia and hyperalgesia. RT-PCR analysis
      showed increased expression of caspase-1, caspase-12 and caspase-8 genes in the
      orbito-frontal cortex 14 days after spared nerve injury of the sciatic nerve.
      Conversely, the expression of caspase-3 was decreased by spared nerve injury of
      the sciatic nerve in the same brain area. A single subcutaneous injection of
      ozone performed 12 h after the surgical procedure decreased mechanical allodynia
      and normalized the mRNA caspase-1, caspase-12 and caspase-8 gene levels, but did
      not the decrease caspase-3 level, 14 days post-spared nerve injury. Ozone also
      reduced IL-1beta staining in the orbito-frontal cortex in neuropathic mice. This
      study provides evidence that a single subcutaneous administration of ozone
      decreased neuropathic pain type behaviour, normalized the expression of pro
      inflammatory caspases and reduced IL-1beta staining in the orbito-frontal cortex
      astrocytes in SNI mice. These preliminary data show that peripheral neuropathy
      induced over-expression of pro-inflammatory/pro-apoptotic caspases in the orbito
      frontal cortex and that ozone, by mechanisms that are as yet unknown, can
      regulate the expression of the genes that play a pivotal role in the onset and
      maintenance of allodynia.

PMID- 19100258
TI  - Transition of cervical carcinoma in situ to invasive cancer: role of p16 INK4a
      expression in progression and in recurrence.
AB  - To investigate the expression of p16(INK4a) in cervical carcinoma and its
      relation to the transition of carcinoma in situ to invasive carcinoma, and its
      role in recurrence of cervical lesions as well, a series of 90 patients with
      cervical carcinoma (49 with in situ lesion and 41 with invasive lesion) were
      selected from July 2001 and September 2002. Groups with in situ and invasive
      lesions were paired for a series of risk variables for cervical cancer and
      followed up for 60 months. The follow-up visits occurred every 6 months in the
      first three years and annually up to the fifth year. It was observed that 87.9%
      of the patients with invasive lesion showed overexpression of p16(INK4a), in
      comparison with 37.6% of those with in situ lesion (X(2): 13.68; 2 df; p=0.0002;
      OR: 12.08), demonstrating overexpression of p16(INK4a) as a risk of invasion of
      the basal layer by dysplastic cells. We also observed an association between
      overexpression of p16(INK4a) and staging of cancer (X(2): 18.38; 6 df; p=0.0003).
      A prospective analysis, when controlled for interaction with cervical lesion
      groups (by Cox regression), demonstrated a risk of recurrence of 4.83 times
      attributed to overexpression of p16(INK4a), albeit not statistically significant
      (p=0.14).

PMID- 19100259
TI  - Cdc42 is crucial for the maturation of primordial cell junctions in keratinocytes
      independent of Rac1.
AB  - Cell-cell contacts are crucial for the integrity of all tissues. Contrasting
      reports have been published about the role of Cdc42 in epithelial cell-cell
      contacts in vitro. In keratinocytes, it was suggested that Rac1 and not Cdc42 is
      crucial for the formation of mature epithelial junctions, based on dominant
      negative inhibition experiments. Deletion of the Cdc42 gene in keratinocytes in
      vivo slowly impaired the maintenance of cell-cell contacts by an increased
      degradation of beta-catenin. Whether Cdc42 is required for the formation of
      mature junctions was not tested. We show now that Cdc42-deficient immortalized
      and primary keratinocytes form only punctate primordial cell contacts in vitro,
      which cannot mature into belt-like junctions. This defect was independent of
      enhanced degradation of beta-catenin, but correlated to an impaired activation
      and localization of aPKCzeta in the Cdc42-null keratinocytes. Inhibition of
      aPKCzeta by the inhibitor Go6983 reproduced the phenotype, suggesting that
      decreased activation of aPKCzeta was sufficient to explain the defective
      junctional maturation. In the absence of Cdc42, Rac1 activation was strongly
      decreased, indicating that Cdc42 is upstream of Rac1 activation. These data
      reveal that Cdc42 is crucial for the formation of mature epithelial cell
      junctions between keratinocytes by regulating activation of aPKCzeta.

PMID- 19100260
TI  - TRIM39 is a MOAP-1-binding protein that stabilizes MOAP-1 through inhibition of
      its poly-ubiquitination process.
AB  - Bax, a multi-domain pro-apoptotic Bcl-2 family member, is a key regulator for the
      release of apoptogenic factors from mitochondria. MOAP-1, which was first
      isolated from a screen for Bax-associating proteins, interacts with Bax upon
      apoptotic induction. MOAP-1 is a short-lived protein that is constitutively
      degraded by the ubiquitin-proteasome system. Apoptotic stimuli upregulate MOAP-1
      rapidly through inhibition of its poly-ubiquitination process. However, cellular
      factors that regulate the stability of MOAP-1 have not yet been identified. In
      this study, we report the identification of TRIM39 as a MOAP-1-binding protein.
      TRIM39 belongs to a family of proteins characterized by a Tripartite Motif
      (TRIM), consisting of RING domain, B-box and coiled-coil domain. Several TRIM
      family members are known to demonstrate E3 ubiquitin ligase activity.
      Surprisingly, TRIM39 significantly extends the half-life of MOAP-1 by inhibiting
      its poly-ubiquitination process. In agreement with its effect on enhancing MOAP-1
      stability, TRIM39 sensitizes cells to etoposide-induced apoptosis. Conversely,
      knockdown of TRIM39 reduces the sensitivity of cells to etoposide-stimulated
      apoptosis. Furthermore, TRIM39 elevates the level of MOAP-1 in mitochondria and
      promotes cytochrome c release from isolated mitochondria stimulated by
      recombinant Bax. Together, these data suggest that TRIM39 can promote apoptosis
      signalling through stabilization of MOAP-1.

PMID- 19100261
TI  - Basic fibroblast growth factor-enhanced neurogenesis contributes to cognitive
      recovery in rats following traumatic brain injury.
AB  - Stem/progenitor cells reside throughout the adult CNS and are actively dividing
      in the subventricular zone (SVZ) and the dentate gyrus (DG) of the hippocampus.
      This neurogenic capacity of the SVZ and DG is enhanced following traumatic brain
      injury (TBI) suggesting that the adult brain has the inherent potential to
      restore populations lost to injury. This raises the possibility of developing
      strategies aimed at harnessing the neurogenic capacity of these regions to repair
      the damaged brain. One strategy is to enhance neurogenesis with mitogenic
      factors. As basic fibroblast growth factor (bFGF) is a potent stem cell mitogen,
      we set out to determine if an intraventricular administration of bFGF following
      TBI could affect the levels of injury-induced neurogenesis in the SVZ and DG, and
      the degree to which this is associated with cognitive recovery. Specifically,
      adult rats received a bFGF intraventricular infusion for 7 days immediately
      following TBI. BrdU was administered to animals daily at 2-7 days post-injury to
      label cell proliferation. At 1 or 4 weeks post-injury, brain sections were
      immunostained for BrdU and neuronal or astrocytic markers. We found that injured
      animals infused with bFGF exhibited significantly enhanced cell proliferation in
      the SVZ and the DG at 1 week post-TBI as compared to vehicle-infused animals.
      Moreover, following bFGF infusion, a greater number of the newly generated cells
      survived to 4 weeks post-injury, with the majority being neurons. Additionally,
      animals infused with bFGF showed significant cognitive improvement. Collectively,
      the current findings suggest that bFGF-enhanced neurogenesis contributes to
      cognitive recovery following TBI.

PMID- 19100262
TI  - An investigation of EEG dynamics in an animal model of temporal lobe epilepsy
      using the maximum Lyapunov exponent.
AB  - Analysis of intracranial electroencephalographic (iEEG) recordings in patients
      with temporal lobe epilepsy (TLE) has revealed characteristic dynamical features
      that distinguish the interictal, ictal, and postictal states and inter-state
      transitions. Experimental investigations into the mechanisms underlying these
      observations require the use of an animal model. A rat TLE model was used to test
      for differences in iEEG dynamics between well-defined states and to test specific
      hypotheses: 1) the short-term maximum Lyapunov exponent (STL(max)), a measure of
      signal order, is lowest and closest in value among cortical sites during the
      ictal state, and highest and most divergent during the postictal state; 2)
      STL(max) values estimated from the stimulated hippocampus are the lowest among
      all cortical sites; and 3) the transition from the interictal to ictal state is
      associated with a convergence in STL(max) values among cortical sites. iEEGs were
      recorded from bilateral frontal cortices and hippocampi. STL(max) and T-index (a
      measure of convergence/divergence of STL(max) between recorded brain areas) were
      compared among the four different periods. Statistical tests (ANOVA and multiple
      comparisons) revealed that ictal STL(max) was lower (p<0.05) than other periods,
      STL(max) values corresponding to the stimulated hippocampus were lower than those
      estimated from other cortical regions, and T-index values were highest during the
      postictal period and lowest during the ictal period. Also, the T-index values
      corresponding to the preictal period were lower than those during the interictal
      period (p<0.05). These results indicate that a rat TLE model demonstrates several
      important dynamical signal characteristics similar to those found in human TLE
      and support future use of the model to study epileptic state transitions.

PMID- 19100263
TI  - Mouse olfactory ensheathing glia enhance axon outgrowth on a myelin substrate in
      vitro.
AB  - Olfactory ensheathing glia (OEG) express cell adhesion molecules and secrete
      growth factors that support newly generated olfactory axons and are a promising
      therapeutic treatment to facilitate axonal regeneration after spinal cord injury
      (SCI). To study the molecular mechanisms underlying the ability of OEG to enhance
      axonal outgrowth, we designed an outgrowth assay using spinal cord myelin as a
      substrate to mimic an injury environment. We asked if olfactory bulb-derived OEG
      could enhance outgrowth of dorsal root ganglion (DRG) axons on myelin. When grown
      on myelin alone DRG axons have limited outgrowth potential. However, when OEG are
      co-cultured with DRG on myelin, twice as many neurons generate axons and their
      average length is almost twice that grown on myelin alone. We used this OEG/DRG
      co-culture to determine if a cell adhesion molecule expressed by OEG, L1, and a
      factor secreted by OEG, brain-derived neurotrophic factor (BDNF), contribute to
      the ability of OEG to enhance axonal outgrowth on myelin. Using OEG and DRG from
      L1 mutant mice we found that L1 expression does not contribute to OEG growth
      promotion. However, both BDNF and its receptor, TrkB, contribute to OEG-enhanced
      axon regeneration as function-blocking antisera against either component
      significantly decreased outgrowth of DRG axons. Additional BDNF further enhanced
      DRG axon growth on myelin alone and on myelin co-cultured with OEG. This simple
      mouse outgrowth model can be used to determine the molecules that contribute to
      OEG-enhancement of axonal outgrowth, test therapeutic compounds, and compare the
      outgrowth potential of other treatments for SCI.

PMID- 19100264
TI  - Long-term depression of excitatory synaptic transmission in rat hippocampal CA1
      neurons following sleep-deprivation.
AB  - In rat hippocampal CA1 neurons, excitatory synaptic transmission is depressed
      following a 20 Hz, 30 s stimulation in the stratum radiatum. This depression
      lasts for at least 25 min post-tetanus (long-term depression, LTD). The LTD is
      significantly enhanced by about 20% if rats were sleep-deprived for 12 h prior to
      recording. The increase in LTD following sleep-deprivation is a new finding which
      can have implications for hippocampal neuronal excitability, network activity,
      and induction of long-term potentiation and may account for post-sleep
      deprivation amnesia.

PMID- 19100265
TI  - Elevated serum alanine aminotransferase and gamma-glutamyltransferase and
      mortality in the United States population.
AB  - BACKGROUND & AIMS: Elevated serum alanine aminotransferase (ALT) and gamma
      glutamyltransferase (GGT) activities are markers of liver injury, but may also be
      associated with other diseases and death. In a prospective, national, population
      based sample, we examined whether elevated ALT and GGT were associated with
      increased risk of all-cause and disease-specific mortality. METHODS: Death
      certificate-based 12-year mortality was analyzed among 14,950 adult participants
      in the third US National Health and Nutrition Examination Survey, 1988-1994, who
      were negative for markers of viral hepatitis B and C. Abnormal ALT was defined as
      >30 U/L in men or >19 U/L in women, and abnormal GGT as >51 U/L in men or >33 U/L
      in women. RESULTS: Cumulative mortality was 13.9% from all causes, including 4.2%
      from cardiovascular disease, 4.2% from neoplasms, 0.44% from diabetes, and 0.13%
      from liver disease. In multivariate-adjusted analyses, elevated ALT was not
      associated with all-cause mortality (hazard ratio [HR], 1.2; 95% confidence
      interval [CI], 0.88-1.6). ALT elevation was associated with deaths from liver
      disease (HR, 8.2; 95% CI, 2.1-31.9), but not from cardiovascular disease (HR,
      0.90; 95% CI, 0.56-1.4), neoplasms (HR, 1.0; 95% CI, 0.65-1.5), or diabetes (HR,
      2.4; 95% CI, 0.65-9.1). All-cause mortality increased with elevated GGT (HR, 1.5;
      95% CI, 1.2-1.8), as did mortality from liver disease (HR, 13.0; 95% CI, 2.4
      71.5), neoplasms (HR, 1.5; 95% CI, 1.01-2.2), and diabetes (HR, 3.3; 95% CI, 1.4
      7.6), but not from cardiovascular disease (HR, 1.3; 95% CI, 0.80-2.0).
      CONCLUSIONS: In the US population, elevated GGT was associated with mortality
      from all causes, liver disease, cancer, and diabetes, while ALT was associated
      only with liver disease mortality.

PMID- 19100267
TI  - Caution on the assessment of intestinal parasitic load in studying parasite
      mediated sexual selection: the case of Blackbirds coccidiosis.
AB  - The parasite-mediated sexual selection (PMSS) theory has led to an increasing
      number of experimental studies essentially focussed on blood parasites.
      Currently, more research is being carried out on intestinal parasites in
      relationship to this theory. Before testing the theory with gastrointestinal
      parasites, it is important: (i) to determine an optimal research methodology to
      obtain an accurate assessment of parasite burden and (ii) to have information
      about life-history traits of the parasite to interpret data appropriately. In
      this study, we present data on oocyst output of Isosporaturdi in the faeces of
      blackbirds (Turdus merula) that illustrate the importance of developing methods
      that are relevant for a particular model system, instead of relying on existing
      methods that may work in other systems. Our results show that: (i) a single
      droplet of faeces will accurately indicate the parasitic load in blackbirds, (ii)
      oocyst shedding varies greatly within and between days, (iii) the course of
      infection is characterised with two successive peaks of oocyst shedding, (iv)
      infection lasts approximately 1 month and (iv) there is no effect of sex, size of
      infective dose or re-infection on the course of infection. We discuss the
      practical implications of these results in determining the reliability of, and in
      avoiding erroneous conclusions about, PMSS when using intestinal parasites as
      models. In particular, we emphasise that numerous measurements must be performed
      on different days. In addition, faeces must be collected at a particular time of
      day because there is a strong temporal variation in oocyst shedding. Finally, a
      standardised methodology that has been developed for a particular host-parasite
      assemblage does not necessarily work with other biological models. Together, our
      results should encourage future investigators to identify an accurate methodology
      for assessing parasitic load as a first step before testing hypotheses associated
      with the PMSS theory.

PMID- 19100266
TI  - Personality and congenital adrenal hyperplasia: possible effects of prenatal
      androgen exposure.
AB  - Influences of early androgen exposure on personality were investigated.
      Participants were either exposed to abnormal levels of androgens prenatally due
      to congenital adrenal hyperplasia (CAH, 40 females, 29 males), or were unaffected
      relative controls (29 females, 30 males). Compared to female controls, females
      with CAH were less tender-minded (p<.001; 16 Personality Factor Inventory
      (16PF)), and reported greater physical aggression (p=.03; Reinisch Aggression
      Inventory) and less interest in infants (p<.001; Melson's Questionnaire), but did
      not differ in dominance (16PF). Males with CAH did not differ from male controls
      in interest in infants but were less dominant (p=.008), and more tender-minded
      (p=.033) and reported reduced physical aggression (p=.025). Thus, both males and
      females with CAH showed alteration in three of the four constructs assessed.
      Prenatal androgen exposure may shift some, but not all, personality
      characteristics in the male-typical direction in females. It may also be
      associated with a decrease in some aspects of male-typical personality
      development in males, although personality differences in males with CAH could
      relate to illness.

PMID- 19100268
TI  - Circadian variation in shedding of the oocysts of Isospora turdi (Apicomplexa) in
      blackbirds (Turdusmerula): an adaptative trait against desiccation and
      ultraviolet radiation.
AB  - Many parasite species spend part of their life cycle in the external environment
      waiting for a new host. Emergence of parasites often occurs once a day, which may
      help to minimise mortality in an inhospitable environment and increase transition
      rates. Many intestinal parasites in birds are released in faeces only in the late
      afternoon. However, the adaptative significance of this pattern is unclear. One
      hypothesis is that a particular time of emergence may prevent parasite
      desiccation and therefore increase the parasite's life expectancy in the external
      environment. We tested this hypothesis experimentally using the blackbird (Turdus
      merula) infected with Isospora turdi (Protozoa: Apicomplexa). We found that short
      exposure of faeces to natural sunlight has a dramatic effect on oocyst survival.
      This appears to be due to the effect of warmth and ultraviolet (UV) radiation
      with UVB waves being more damaging than UVA. Oocysts contained in faeces shed in
      water are protected from the effect of sunlight. Together, these results suggest
      that the release of oocysts in the late afternoon is an adaptative trait to avoid
      desiccation and UV radiation, thus reducing mortality of the oocysts in the
      external environment.

PMID- 19100269
TI  - Gene gun-supported DNA immunisation of chicken for straightforward production of
      poxvirus-specific IgY antibodies.
AB  - Orthopoxviruses code for numerous immunomodulatory proteins, the structure and
      function of which are clarified inadequately. Antibodies constitute a potent tool
      to study such proteins, enabling conclusions on protein location and time course
      of expression. However, common antibody production in mice or rabbits requires
      tedious protein expression and injection, as well as blood collection at regular
      intervals. To simplify this procedure, IgY antibodies specific for poxviral
      proteins (F1L and p28) were generated by immunisation of chickens, because
      antibody retrieval from eggs allows the non-invasive generation of huge amounts
      of antibodies. The main intentions were (i) to decrease invasiveness, (ii) to
      immunise with native forms of proteins and (iii) to circumvent previous protein
      expression and purification. Therefore, chicken were immunised with DNA
      expression vectors coding for conserved domains of the selected proteins
      delivered for the first time by a gene gun. Four weeks after initial immunisation
      specific antibodies were found in the egg yolk as proven by immunofluorescence
      staining of poxvirus-infected cells. The specific IgY titre rose to 1:80,000 and
      was stable for more than 120 days. With this investigation we present an
      universal procedure for IgY design and production that can be applied for various
      issues in the future.

PMID- 19100270
TI  - Bioinformatics and protein expression analyses implicate LEA proteins in the
      drought response of Collembola.
AB  - Humidity has a large impact on the distribution and abundance of terrestrial
      invertebrates, but the molecular mechanisms governing drought resistance are not
      fully understood. Some attention has been given to the role of the heat shock
      response as a component of desiccation tolerance, but recent focus has been on
      the chaperone-like LEA (late embryogenesis abundant) proteins in anhydrobiotic
      animals. This study investigates the expression of putative LEA proteins as well
      as the heat shock protein Hsp70 during drought stress in soil and surface
      dwelling species of Collembola (springtails). In silico analysis of four EST
      candidates from two species of Collembola showed the presence of a Group 3 LEA
      protein in Megaphorura arctica. In common with other Group 3 LEA proteins, the
      new sequence is predicted to be 100% natively unfolded, with a strong degree of
      lysine and alanine periodicity and with a negative average hydrophobicity of 
      1.273. The sequence clusters with members of the Group 3 LEA in plants.
      Furthermore, cross-species Western blotting showed drought-induced expression of
      putative LEA proteins in six species of Collembola. In the surface dwelling
      species, Orchesella cincta, degree of dehydration and length of exposure
      correlated with level of putative LEA protein. Hsp70 was also found to increase
      in individuals of O. cincta and Folsomia candida that had been exposed to drought
      conditions for 6 days. These results show the presence of a LEA protein-coding
      region in Collembola, but also indicate that several proteins are involved in
      response to dehydration stress, including Hsp70.

PMID- 19100271
TI  - Distinct contractile and molecular differences between two goat models of atrial
      dysfunction: AV block-induced atrial dilatation and atrial fibrillation.
AB  - Atrial dilatation is an independent risk factor for thromboembolism in patients
      with and without atrial fibrillation (AF). In many patients, atrial dilatation
      goes along with depressed contractile function of the dilated atria. While some
      mechanisms causing atrial contractile dysfunction in fibrillating atria have been
      addressed previously, the cellular and molecular mechanisms of atrial contractile
      remodeling in dilated atria are unknown. This study characterized in vivo atrial
      contractile function in a goat model of atrial dilatation and compared it to a
      goat model of AF. Differences in the underlying mechanisms were elucidated by
      studying contractile function, electrophysiology and sarcoplasmic reticulum (SR)
      Ca2+ load in atrial muscle bundles and by analyzing expression and
      phosphorylation levels of key Ca2+-handling proteins, myofilaments and the
      expression and activity of their upstream regulators. In 7 chronically
      instrumented, awake goats atrial contractile dysfunction was monitored during 3
      weeks of progressive atrial dilatation after AV-node ablation (AV block goats
      (AVB)). In open chest experiments atrial work index (AWI) and refractoriness were
      measured (10 goats with AVB, 5 goats with ten days of AF induced by repetitive
      atrial burst pacing (AF), 10 controls). Isometric force of contraction (FC),
      transmembrane action potentials (APs) and rapid cooling contractures (RCC, a
      measure of SR Ca2+ load) were studied in right atrial muscle bundles. Total and
      phosphorylated Ca2+-handling and myofilament protein levels were quantified by
      Western blot. In AVB goats, atrial size increased by 18% (from 26.6+/-4.4 to
      31.6+/-5.5 mm, n=7 p<0.01) while atrial fractional shortening (AFS) decreased
      (from 18.4+/-1.7 to 12.8+/-4.0% at 400 ms, n=7, p<0.01). In open chest
      experiments, AWI was reduced in AVB and in AF goats compared to controls (at 400
      ms: 8.4+/-0.9, n=7, and 3.2+/-1.8, n=5, vs 18.9+/-5.3 mmxmmHg, n=7, respectively,
      p<0.05 vs control). FC of isolated right atrial muscle bundles was reduced in AVB
      (n=8) and in AF (n=5) goats compared to controls (n=9) (at 2 Hz: 2.3+/-0.5 and
      0.7+/-0.2 vs 5.5+/-1.0 mN/mm2, respectively, p<0.05). APs were shorter in AF, but
      unchanged in AVB goats. RCCs were reduced in AVB and AF versus control (AVB,
      3.4+/-0.5 and AF, 4.1+/-1.4 vs 12.2+/-3.2 mN/mm2, p<0.05). Protein levels of
      protein kinase A (PKA) phosphorylated phospholamban (PLB) were reduced in AVB
      (n=8) and AF (n=8) vs control (n=7) by 37.9+/-12.4% and 29.7+/-10.1%,
      respectively (p<0.01), whereas calmodulin-dependent protein kinase II (CaMKII)
      phosphorylated ryanodine channels (RyR2) were increased by 166+/-55% in AVB (n=8)
      and by 146+/-56% in AF (n=8) goats (p<0.01). PKA-phosphorylated myosin-binding
      protein-C and troponin-I were reduced exclusively in AVB goat atria (by 75+/-10%
      and 55+/-15%, respectively, n=8, p<0.05). Atrial dilatation developing during
      slow ventricular rhythm after complete AV block as well as AF-induced remodeling
      are associated with atrial contractile dysfunction. Both AVB and AF goat atria
      show decreased SR Ca2+ load, likely caused by PLB dephosphorylation and RYR2
      hyperphosphorylation. While shorter APs further compromise contractility in AF
      goat atria, reduced myofilament phosphorylation may impair contractility in AVB
      goat atria. Thus, atrial hypocontractility appears to have distinct molecular
      contributors in different types of atrial remodeling.

PMID- 19100272
TI  - Structure of PBP-A from Thermosynechococcus elongatus, a penicillin-binding
      protein closely related to class A beta-lactamases.
AB  - Molecular evolution has always been a subject of discussions, and researchers are
      interested in understanding how proteins with similar scaffolds can catalyze
      different reactions. In the superfamily of serine penicillin-recognizing enzymes,
      D-alanyl-D-alanine peptidases and beta-lactamases are phylogenetically linked but
      feature large differences of reactivity towards their respective substrates. In
      particular, while beta-lactamases hydrolyze penicillins very fast, leading to
      their inactivation, these molecules inhibit d-alanyl-d-alanine peptidases by
      forming stable covalent penicilloyl enzymes. In cyanobacteria, we have discovered
      a new family of penicillin-binding proteins (PBPs) presenting all the sequence
      features of class A beta-lactamases but having a six-amino-acid deletion in the
      conserved Omega-loop and lacking the essential Glu166 known to be involved in the
      penicillin hydrolysis mechanism. With the aim of evolving a member of this family
      into a beta-lactamase, PBP-A from Thermosynechococcus elongatus has been chosen
      because of its thermostability. Based on sequence alignments, introduction of a
      glutamate in position 158 of the shorter Omega-loop afforded an enzyme with a 50
      fold increase in the rate of penicillin hydrolysis. The crystal structures of PBP
      A in the free and penicilloylated forms at 1.9 A resolution and of L158E mutant
      at 1.5 A resolution were also solved, giving insights in the catalytic mechanism
      of the proteins. Since all the active-site elements of PBP-A-L158E, including an
      essential water molecule, are almost perfectly superimposed with those of a class
      A beta-lactamase such as TEM-1, the question why our mutant is still 5 orders of
      magnitude less active as a penicillinase remains and our results emphasize how
      far we are from understanding the secrets of enzymes. Based on the few minor
      differences between the active sites of PBP-A and TEM-1, mutations were
      introduced in the L158E enzyme, but while activities on D-Ala-D-Ala mimicking
      substrates were severely impaired, further improvement in penicillinase activity
      was unsuccessful.

PMID- 19100273
TI  - GABAA receptors in nucleus accumbens shell mediate the hyperphagia and weight
      gain following haloperidol treatment in rats.
AB  - AIMS: Weight gain is a common outcome of antipsychotics therapy in schizophrenic
      patients. However, the underlying neuronal mechanisms are unclear. The present
      study was undertaken to investigate the role of GABA(A) receptors within the
      framework of nucleus accumbens shell (AcbSh) in haloperidol-induced hyperphagia
      and body weight gain in sated rats. MAIN METHODS: In acute studies, GABA(A)
      receptor agonists muscimol, diazepam or antagonist bicuculline were administered
      by AcbSh route, alone or in combination with haloperidol (intraperitoneal/ip).
      Immediately after these treatments, preweighed food was offered to the animals at
      commencement of dark phase. Cumulative food intake was measured at 2 and 6 h post
      injection time-points. Furthermore, effects of subacute haloperidol treatment,
      alone or in combination with muscimol, diazepam or bicuculline, on food intake
      and body weight were investigated. KEY FINDINGS: While acute treatment with
      haloperidol, muscimol or diazepam dose dependently stimulated the food intake,
      bicuculline suppressed the same. Prior administration of muscimol (20 ng/rat,
      intra-AcbSh) and diazepam (5 microg/rat, intra-AcbSh) significantly potentiated,
      whereas bicuculline (40 ng/rat, intra-AcbSh) negated the hyperphagic effect of
      acute haloperidol (0.005 or 0.01 mg/kg/rat, ip). Subacute administration of
      haloperidol (0.01 mg/kg/rat/day, ip) for 15 days produced increase in food intake
      and body weight. Although, concomitant administration of muscimol (20 ng/rat/day,
      intra-AcbSh) or diazepam (5 microg/rat/day, intra-AcbSh) markedly enhanced,
      bicuculline (40 ng/rat/day, intra-AcbSh) prevented the subacute haloperidol
      induced hyperphagia and weight gain. SIGNIFICANCE: The results of present study
      suggest that increased food intake and body weight following haloperidol
      treatment in rats, may be mediated via AcbSh GABA(A) receptors.

PMID- 19100275
TI  - Vision in the palm of your hand.
AB  - Here we show that pointing movements made to visual targets projected onto the
      palm of the hand are more precise and accurate than those made to targets
      projected onto back of the hand. This advantage may be related to the fact that
      the number of cortical bimodal neurons coding both visual and tactile stimuli
      increases with tactile receptor density, which is known to be higher in glabrous
      than in hairy skin.

PMID- 19100274
TI  - Monocular patching may induce ipsilateral "where" spatial bias.
AB  - Spatial bias is an asymmetry of perception and/or representation of spatial
      information - "where" bias -, or of spatially directed actions - "aiming" bias. A
      monocular patch may induce contralateral "where" spatial bias (the Sprague effect
      [Sprague, J. M. (1966). Interaction of cortex and superior colliculus in
      mediation of visually guided behavior in cat. Science, 153(3743), 1544-1547]).
      However, an ipsilateral patch-induced spatial bias may be observed if visual
      occlusion results in top-down, compensatory re-allocation of spatial perceptual
      or representational resources toward the region of visual deprivation. Tactile
      distraction from a monocular patch may also contribute to an ipsilateral bias. To
      examine these hypotheses, neurologically normal adults bisected horizontal lines
      at baseline without a patch, while wearing a monocular patch, and while wearing
      tactile-only and visual-only monocular occlusion. We fractionated "where" and
      "aiming" spatial bias components using a video apparatus to reverse visual
      feedback for half of the test trials. The results support monocular patch-induced
      ipsilateral "where" spatial errors, which are not consistent with the Sprague
      effect. Further, the present findings suggested that the induced ipsilateral bias
      may be primarily induced by visual deprivation, consistent with compensatory
      "where" resource re-allocation.

PMID- 19100276
TI  - Sensory and motor involvement in the enhanced redundant target effect: a study
      comparing anterior- and totally split-brain individuals.
AB  - This study investigated the redundant target effect (RTE) in partial split-brain
      (anterior section sparing the splenium), total split-brain, and neurologically
      intact individuals. All completed an RTE protocol in which targets were presented
      on the midline or in an inter- or intrahemispheric manner. Stimuli of different
      nature (luminance, equiluminant colour, and global motion) were used separately
      in three experiments in order to investigate the contribution of subcortical
      versus cortical pathways. Despite the preservation of the splenium (the portion
      of the corpus callosum assumed to transfer visual information), partial split
      brain individuals showed an enhanced RTE pattern as compared to neurologically
      intact individuals. Total split-brain individuals showed a tendency toward larger
      RTEs with the luminance stimuli than with the colour and motion stimuli, whereas
      this was not the case for partial split-brain individuals, suggesting a
      contribution of the posterior portion of the corpus callosum in the RTE. It is
      therefore likely that both sensory and motor processes contribute to the enhanced
      RTE in split-brain individuals.

PMID- 19100277
TI  - Hearing again with two ears: recovery of spatial hearing after bilateral cochlear
      implantation.
AB  - Bilateral cochlear implants (CI) offer a unique opportunity for the study of
      spatial hearing plasticity in humans. Here we studied the recovery of spatial
      hearing in two sequential bilateral CI recipients, adopting a longitudinal
      approach. Each recipient was tested in a sound-source identification task shortly
      after bilateral activation and at 1, 6, and 12 months follow-up. The results show
      fast recovery (1 month from CI activation) in the recipient who had substantial
      experience with auditory cues in adulthood. By contrast, the bilateral CI
      recipient who developed profound deafness in childhood, regained spatial hearing
      abilities only 12 months after CI activation. These findings provide the first
      direct evidence that recovery of auditory spatial abilities in bilateral CI
      recipients can occur shortly after activation of the two devices. In addition,
      they suggest that previous auditory experience can constrain the time course of
      this recovery.

PMID- 19100278
TI  - Cadmium affects retinogenesis during zebrafish embryonic development.
AB  - Ocular malformations are commonly observed in embryos of aquatic species after
      exposure to toxicants. Using zebrafish embryos as the model organism, we showed
      that cadmium exposure from sphere stage (4 hpf) to end of segmentation stage (24
      hpf) induced microphthalmia in cadmium-treated embryos. Embryos with eye defects
      were then assessed for visual abilities. Cadmium-exposed embryos were
      behaviorally blind, showing hyperpigmentation and loss of camouflage response to
      light. We investigated the cellular basis of the formation of the small eyes
      phenotype and the induction of blindness by studying retina development and
      retinotectal projections. Retinal progenitors were found in cadmium-treated
      embryos albeit in smaller numbers. The number of retinal ganglion cells (RGC),
      the first class of retinal cells to differentiate during retinogenesis, was
      reduced, while photoreceptor cells, the last batch of retinal neurons to
      differentiate, were absent. Cadmium also affected the propagation of neurons in
      neurogenic waves. The neurons remained in the ventronasal area and failed to
      spread across the retina. Drastically reduced RGC axons and disrupted optic stalk
      showed that the optic nerves did not extend from the retina beyond the chiasm
      into the tectum. Our data suggested that impairment in neuronal differentiation
      of the retina, disruption in RGC axon formation and absence of cone
      photoreceptors were the causes of microphthalmia and visual impairment in cadmium
      treated embryos.

PMID- 19100279
TI  - Skin metabolism of aminophenols: human keratinocytes as a suitable in vitro model
      to qualitatively predict the dermal transformation of 4-amino-2-hydroxytoluene in
      vivo.
AB  - 4-Amino-2-hydroxytolune (AHT) is an aromatic amine ingredient in oxidative hair
      colouring products. As skin contact occurs during hair dyeing, characterisation
      of dermal metabolism is important for the safety assessment of this chemical
      class. We have compared the metabolism of AHT in the human keratinocyte cell line
      HaCaT with that observed ex-vivo in human skin and in vivo (topical application
      versus oral (p.o.) and intravenous (i.v.) route). Three major metabolites of AHT
      were excreted, i.e. N-acetyl-AHT, AHT-sulfate and AHT-glucuronide. When 12.5
      mg/kg AHT was applied topically, the relative amounts of each metabolite were
      altered such that N-acetyl-AHT product was the major metabolite (66% of the dose
      in comparison with 37% and 32% of the same applied dose after i.v. and p.o.
      administration, respectively). N-acetylated products were the only metabolites
      detected in HaCaT cells and ex-vivo whole human skin discs for AHT and p
      aminophenol (PAP), an aromatic amine known to undergo N-acetylation in vivo.
      Since N-acetyltransferase 1 (NAT1) is the responsible enzyme, kinetics of AHT was
      further compared to the standard NAT1 substrate p-aminobenzoic acid (PABA) in the
      HaCaT model revealing similar values for K(m) and V(max). In conclusion NAT1
      dependent dermal N-acetylation of AHT represents a 'first-pass' metabolism effect
      in the skin prior to entering the systemic circulation. Since the HaCaT cell
      model represents a suitable in vitro assay for addressing the qualitative
      contribution of the skin to the metabolism of topically-applied aromatic amines
      it may contribute to a reduction in animal testing.

PMID- 19100280
TI  - Solution concentration influences voluntary consumption of nicotine under
      multiple bottle conditions.
AB  - Female Sprague Dawley rats were given a choice between two concentrations of
      nicotine solution (5 microg/ml and 8 microg/ml) and water in a 5-bottle
      arrangement for 25 days. Rats developed clear bottle discrimination, drinking
      more of the 5 microg/ml nicotine solution than water or the higher concentration
      nicotine solution. Further, intake patterns were sensitive to exposure.
      Differences in consumption of the three solutions (5 microg/ml vs. 8 microg/ml
      vs. water) were minimal during initial exposure days but became clear and stable
      with chronic exposure. Control rats given 5 bottles of water drank equally from
      all bottles and showed no development of preference for bottle position. Results
      suggest that both environmental availability and post-ingestional effects of
      nicotine contribute to the voluntarily oral consumption of nicotine solutions by
      rats. The influence of these two factors, however, is modulated by exposure.
      Availability appears to drive consumption initially, but the impact of
      concentration exerts more control over consumption with continued exposure. These
      data support the utility of oral methods of nicotine self-administration in the
      laboratory rat and suggest the need for further investigations into the
      biological impact of nicotine consumed orally.

PMID- 19100282
TI  - Randomized trial of three strategies to promote physical activity in general
      practice.
AB  - OBJECTIVE: To evaluate three strategies for promoting physical activity (PA) in a
      primary care setting. METHOD: Data were collected between 2002 and 2004 from 136
      patients attending two general practices in Brisbane, Australia. Inactive
      patients (50-70 years) were randomly allocated to one of three hierarchical
      intervention groups: the general practitioner (GP) group received 'brief' advice;
      the GP+ES group also received behavior change advice from an exercise scientist
      (ES); and the GP+ES+P group also received a pedometer. Self-reported PA and its
      determinants were measured at baseline and weeks 12 and 24. Cardio-respiratory
      variables were measured at baseline and week 12. RESULTS: Overall, mean PA time
      increased by 84 and 128 min/week at weeks 12 and 24 (p<.01) with no significant
      group differences. Small improvements in blood pressure and post-exercise heart
      rate were observed. At week 24, the GP+ES+P group were more likely to report
      meeting PA guidelines than the GP group (OR=2.39 95% CI: 1.01, 5.64). CONCLUSION:
      PA levels can be increased in mid- to older-age adults, either by brief advice
      from motivated GPs alone, or from collaboration between GPs and ESs. The most
      intense intervention (GP+ES+P) showed the most promising results.

PMID- 19100281
TI  - Methylphenidate potentiates morphine-induced antinociception, hyperthermia, and
      locomotor activity in young adult rats.
AB  - The goal of this study was to determine if the exaggerated morphine-induced
      conditioned place preference (CPP) response seen in adult rats after preweanling
      methylphenidate exposure is unique to reward-mediated behaviors or is indicative
      of generalized changes in opioid-mediated behaviors. Rats were exposed to saline
      or methylphenidate (2.0 or 5.0 mg/kg) for 10 consecutive days starting on
      postnatal (PD) 11 with testing beginning on PD 60. In Experiment 1, morphine
      induced (0, 2.5, 5.0 or 10.0 mg/kg) antinociception was assessed using the tail
      immersion and hot plate tasks. In Experiment 2, morphine-induced (0, 2.5, 5.0, or
      10.0 mg/kg) hyperthermia and locomotor activity were measured. Morphine caused an
      increase in antinociception, with early methylphenidate (5.0 mg/kg) exposure
      potentiating the effects of 5.0 mg/kg morphine. Rectal temperatures were elevated
      after morphine, with the greatest increase occurring in male rats.
      Methylphenidate potentiated the hyperthermic effects of morphine (10.0 mg/kg) but
      only in males. Moderate doses (2.5 and 5.0 mg/kg) of morphine increased the
      locomotor activity of adult rats, while a higher dose (10.0 mg/kg) decreased
      locomotion. Interestingly, methylphenidate-pretreated females showed increased
      locomotor activity relative to controls. These results suggest that early
      methylphenidate exposure induces general changes in opioid system functioning
      that are not specific to reward-mediated behaviors.

PMID- 19100283
TI  - The effect of rutin on arginine kinase: inhibition kinetics and thermodynamics
      merging with docking simulation.
AB  - Arginine kinase (AK; EC 2.7.3.3) is a key enzyme in the cellular energy
      metabolism of insects. Screening on potential effective inhibitors of AK may
      provide a pathway for novel, environmentally friendly insecticides. The results
      in this study indicated that rutin, as a noncompetitive inhibitor, interacts with
      AK mainly by a hydrophobic force forming an intermolecular complex with AK, which
      is according to the thermodynamic parameters obtained. Using a flexible docking
      method (AutoDock) the interaction between rutin and AK were further analyzed,
      which suggested in order to screen effective inhibitors, flexible active sites of
      AK (Ser63, Gly64, Val65, Tyr68) should be taken in account.

PMID- 19100284
TI  - The in vitro and in ovo responses of chickens to TLR9 subfamily ligands.
AB  - Although Toll-like receptors (TLRs) have been well characterised in mammals, less
      work has been carried out in non-mammalian species, such as chickens. In this
      study the response of chicken cells to the TLR9 subfamily of ligands was
      characterised in vitro and in ovo. It was found that even though chickens appear
      to have only one functional receptor to represent the TLR9 subfamily, stimulation
      of chicken splenocytes with TLR7 and TLR9 ligands induced proinflammatory
      cytokine production and cell proliferation, similar to that observed when the
      homologous mammalian receptors are stimulated. Furthermore, we demonstrated that
      the in ovo administration of these TLR ligands elicits a response, such as
      cytokine production, that can be detected post-hatch. The current knowledge of
      the action of TLR ligands in mammals, in conjunction with their immunomodulating
      ability shown in this study, draws attention to their potential use as
      therapeutic agents for the poultry industry.

PMID- 19100285
TI  - The RepA_N replicons of Gram-positive bacteria: a family of broadly distributed
      but narrow host range plasmids.
AB  - The pheromone-responsive conjugative plasmids of Enterococcus faecalis and the
      multiresistance plasmids pSK1 and pSK41 of Staphylococcus aureus are among the
      best studied plasmids native to Gram-positive bacteria. Although these plasmids
      seem largely restricted to their native hosts, protein sequence comparison of
      their replication initiator proteins indicates that they are clearly related.
      Homology searches indicate that these replicons are representatives of a large
      family of plasmids and a few phage that are widespread among the low G+C Gram
      positive bacteria. We propose to name this family the RepA_N family of replicons
      after the annotated conserved domain that the initiator protein contains.
      Detailed sequence comparisons indicate that the initiator protein phylogeny is
      largely congruent with that of the host, suggesting that the replicons have
      evolved along with their current hosts and that intergeneric transfer has been
      rare. However, related proteins were identified on chromosomal regions bearing
      characteristics indicative of ICE elements, and the phylogeny of these proteins
      displayed evidence of more frequent intergeneric transfer. Comparison of
      stability determinants associated with the RepA_N replicons suggests that they
      have a modular evolution as has been observed in other plasmid families.

PMID- 19100286
TI  - Early exposure to ethanol but not red wine at the same alcohol concentration
      induces behavioral and brain neurotrophin alterations in young and adult mice.
AB  - Ethanol exposure during pregnancy is one of the major causes of mental
      retardation in western countries by inducing fetal-alcohol-like-syndromes. Red
      wine is known to contain ethanol but also compounds with putative antioxidant
      properties. It has also been shown that nerve growth factor (NGF) and brain
      derived neurotrophic factor (BDNF) are severely affected by ethanol during
      prenatal and postnatal life. The aim of the current study was to investigate in
      male CD1 mice brain alterations in NGF and BDNF due to chronic early exposure to
      ethanol solution (11 vol%) or to red wine at the same alcohol concentration
      starting from 60 days before pregnancy up to pups weaning. Data revealed no
      differences between groups of dams in pregnancy duration, neither in pups
      delivery, pups mortality and sex ratio. Data also showed that adult animals
      exposed to only ethanol had disrupted levels of both NGF and BDNF in the
      hippocampus and other brain areas. This profile was associated with impaired ChAT
      immunopositivity in the septum and Nuclei Basalis and with altered cognition and
      emotional behavior. Quite interestingly mice exposed to red wine had no change in
      the behavior or in ChAT immunopositivity but a decrease in hippocampal BDNF and a
      mild NGF decrease in the cortex. Also NGF-induced neuritic outgrowth in PC-12
      cells was still present when exposed to red wine but not when exposed to ethanol
      solution only. Data suggest differences in ethanol-induced neurotoxicity between
      red wine and ethanol solution only.

PMID- 19100287
TI  - Long-term cognitive deficits accompanied by reduced neurogenesis after soman
      poisoning.
AB  - To date, treatment of organophosphate (OP) poisoning shows several shortcomings,
      and OP-victims might suffer from lasting cognitive deficits and sleep-wake
      disturbances. In the present study, long-term effects of soman poisoning on
      learning ability, memory and neurogenesis were investigated in rats, treated with
      the anticholinergic atropine and the oxime HI-6 for reactivation of soman
      inhibited acetylcholinesterase. We also investigated whether sub-chronic
      treatment with the reported neurogenesis enhancer olanzapine would stimulate
      neurogenesis and possibly normalize the anticipated long-term deleterious effects
      of soman intoxication. Animals were treated with HI-6 (125 mg/kg i.p.), followed
      after 30 min by soman (200 microg/kg s.c.) and atropine sulphate (16 mg/kg i.m.)
      1 min thereafter. Soman poisoning led to an elevation of extracellular
      acetylcholine levels to 1500% over baseline values as assessed by striatal
      microdialysis. Brain acetylcholinesterase was inhibited over 95%. This was
      accompanied by short recurrent seizures lasting for 40 min. Osmotic minipumps
      releasing olanzapine (7.5 mg/kg/day) or vehicle were subcutaneously implanted 24
      h post-intoxication. After drug delivery for 4 weeks, newborn cells were BrdU
      labeled. Learning and memory performance were assessed 8 weeks after soman
      poisoning, followed by analysis of surviving newborn cells (BrdU) and
      neurogenesis (doublecortin, DCX). Eight weeks after soman-intoxication a
      significantly impaired learning ability was found that was paralleled by
      significantly lower numbers of DCX-positive cells but no changes in the number of
      BrdU-labeled cells. Apparently, the present Olanzapine regime was ineffective. We
      conclude that soman poisoning has long lasting effects on learning ability, a
      finding that was accompanied by impaired neurogenesis. Although we confirm a
      correlation between impaired neurogenesis and cognitive deficits, establishing
      the true causal relationship between these processes in OP exposed animals awaits
      future research.

PMID- 19100288
TI  - Interference of ethanol and methylmercury in the developing central nervous
      system.
AB  - Studies involving alcohol and its interactions with other neurotoxicants
      represent the focus of several works of research due to the fact that the use of
      alcohol can sometimes leads to serious health problems. Fetal exposure to alcohol
      and mercury has a high incidence in some regions of Brazil, where there are
      pregnant women who are alcoholics and live in mining areas. This work was
      conducted to examine the effects of combined exposure to ethanol (EtOH) and
      methylmercury (MeHg) in rats during the development of the central nervous system
      (CNS). Experimental behavioral animal models/tests were used in order to examine
      locomotion, anxiety, depression and memory. Pregnant rats received tap water or
      EtOH 22.5% w/v (6.5 g/kg per day), by gavage) during pregnancy and breast
      feeding. On the 15th day of pregnancy, some groups received 8 mg/kg of MeHg (by
      gavage). The groups were as follows: control, EtOH, MeHg and EtOH+MeHg. The
      experimental results showed that the EtOH, MeHg and EtOH+MeHg groups reduced the
      percentage of frequency and time spent in the open arms entries of the elevated
      plus-maze (EPM) test, when compared to the control group. This result suggests an
      anxiogenic behavioral response. The MeHg group increased locomotor activity in
      the arena and the immobility time in the forced swimming test, suggestive of
      depression-like behavior. The EtOH+MeHg group showed greater reductions in the
      percentages of frequency and time spent in the open arms entries in the EPM test,
      suggesting a sedative-behavior since the frequency of enclosed arm entries was
      affected. In the inhibitory avoidance task, the EtOH+MeHg group reduced the
      latency of the step-down response onto the grid floor, suggesting a cognitive and
      behavior dysfunctions. Taken together, the results suggest that EtOH and/or MeHg
      intoxication during the developing CNS may be a risk for deficits related to
      locomotor impairment, anxiety, depression and neurocognitive functions. There is
      a possibility that EtOH may prevent some of the MeHg responses, but the precise
      mechanism of action involved in this process needs to be considered for future
      research.

PMID- 19100289
TI  - A highly sensitive and dynamic immunofluorescent cytometric bead assay for the
      detection of HIV-1 p24.
AB  - Nucleic acid measurements are used to follow HIV-1 viral load in clinical
      applications while p24 ELISA is commonly used to monitor HIV-1 replication in
      research settings. Current ELISA assays are expensive and offer a narrow dynamic
      measurement range. This report describes a simple, sensitive and inexpensive bead
      based assay offering a wide dynamic measurement range. This cytometric bead assay
      allows the detection of p24 concentrations over 4 orders of magnitude from less
      than 0.4pg to up to 20,000pgml(-1) in a volume of 50microl and can be combined
      with other measurements.

PMID- 19100290
TI  - Use of conserved genomic regions and degenerate primers in a PCR-based assay for
      the detection of members of the genus Caulimovirus.
AB  - The genus Caulimovirus consists of several distinct virus species with a double
      stranded DNA genome that infect diverse plant species. A comparative analysis of
      the sequences of known Caulimovirus species revealed two regions that are
      conserved in all Caulimovirus species with the exception of Strawberry vein
      banding virus. Degenerate primers based on these two regions were designed and
      tested in a polymerase chain reaction-based assay for broad spectrum detection of
      members of this genus. Cauliflower mosaic virus, Figwort mosaic virus and three
      distinct caulimoviruses associated with dahlia (Dahlia variabilis) were used to
      show the utility of this test in detecting diverse caulimoviruses. The primer
      pair gave an amplicon of expected size (840bp). Amplicons from each virus were
      cloned and sequenced to verify their identity. The primer pair and the PCR assay
      provide approach for the broad spectrum detection of several members of the genus
      Caulimovirus.

PMID- 19100291
TI  - Nicotine does not improve recovery from learned nonuse nor enhance constraint
      induced therapy after motor cortex stroke in the rat.
AB  - Nicotine, a cholinergic agonist, rapidly crosses the blood-brain barrier,
      promotes neuronal plasticity and has been suggested to enhance behavior in a
      variety of neurological conditions. Nicotine has also been suggested to benefit
      functional recovery in rodent models of stroke. At present there has been no
      systematic investigation of the potential benefits of nicotine therapy in both
      the acute and chronic post-stroke period. This was the objective of the present
      study and to that end, the effects of nicotine administration prior to and
      following motor cortex stroke were examined in a skilled reaching task. The task
      provides a thorough assessment of learned nonuse and constraint-induced recovery
      of behavior as determined by both end-point and movement element analysis.
      Nicotine (0.3 mg/kg p.o.) was administered twice daily during reach training and
      following motor cortex stroke. Rats were divided into four groups based on their
      pre-/post-stroke treatment: nicotine/nicotine, nicotine/vehicle,
      vehicle/nicotine, vehicle/vehicle. After stroke, nicotine did not counteract
      learned nonuse, facilitate constraint-induced therapy, or improve long-term
      recovery as measured by end-point analysis and movement element analysis. The
      results are discussed in relation to the problem of identifying
      pharmacotherapeutic agents that augment rehabilitation following stroke.

PMID- 19100293
TI  - Targeting oxidative/nitrergic stress ameliorates motor impairment, and attenuates
      synaptic mitochondrial dysfunction and lipid peroxidation in two models of
      Huntington's disease.
AB  - In this study, we reproduced two toxic models resembling some motor/kinetic
      deficits of Huntington's disease induced by bilateral intrastriatal injections of
      either quinolinic acid (QUIN, 120 nmol/microl per side) or 3-nitropropionic acid
      (3-NP, 250 nmol/microl per side) to rats. Motor skills (including total distance
      walked/traveled and total horizontal and vertical activities) were evaluated in a
      box-field system at 1 and 7 days post-lesion. In order to investigate whether
      these alterations were associated with the oxidative/nitrergic stress evoked by
      the nitrogen reactive species peroxynitrite (ONOO(-)) in the striatum, some rats
      were pretreated with the ONOO(-) decomposition catalyst iron porphyrinate
      (Fe(TPPS), 10 mg/kg, i.p.) 120 min prior to toxins infusion. With the aim to
      further characterize some possible mechanisms by which motor tasks were affected
      and/or preserved, biochemical analysis of peroxidative damage to lipids and
      mitochondrial dysfunction were both assessed in synaptic membranes isolated from
      the striata of QUIN-, 3-NP- and/or Fe(TPPS)-treated animals. Our results show
      that targeting oxidative/nitrergic stress by Fe(TPPS) in these toxic models
      results in amelioration of motor deficits linked to inhibition of peroxidative
      damage and recovery of mitochondrial function in synaptic membranes. Based on
      these findings, we hypothesize that the protection exerted by Fe(TPPS) on the
      biochemical markers analyzed reflects the possible preservation of the functional
      status of the nerve tissue by limiting the deleterious actions of ONOO(-),
      further accounting for partial recovery of integrative motor functions.

PMID- 19100292
TI  - Sigma-1 receptor knockout mice display a depressive-like phenotype.
AB  - Activation of sigma-1 receptors (Sig-1R) reportedly has antidepressant-like
      action. Limited data suggest that Sig-1Rs also modulate anxiety-related
      behaviors. The present experiments measured depressive-like, anxiety-like and
      motor behavior in Sig-1R knockout mice and their wildtype littermates. Sig-1R
      knockout mutants showed increased immobility in the forced swimming test, a
      depressive-like phenotype, but normal anxiety-like behavior in the elevated plus
      maze and light/dark box tests and normal locomotor activity. The results further
      suggest that Sig-1Rs inversely modulate depressive-like behavior.

PMID- 19100295
TI  - Altered leptin secretion in hyperinsulinemic mice under hypoxic conditions.
AB  - OBJECTIVE: Hypoxia and insulin are known key players in the activation leptin
      transcription and translation in vivo and in vitro. These insulin- and hypoxia
      dependent effects are leptin transcription are mediated via independent elements
      on the leptin-promotor, even more coincubation of the two stimuli in vitro
      results in a supraadditive effect on leptin transcription. The aim of this study
      was to examine whether hyperinsulinemia is able to interfere with the hypoxia
      driven expression of leptin in adipose and extra-adipose tissue in vivo. RESEARCH
      METHODS AND PROCEDURES: We used the KK/HlJ mouse strain as a model for
      hyperinsulinemia and C57BL/6J mice as control. These two groups were exposed to
      hypoxia for 12 h. Serum levels of insulin and leptin were analyzed by ELISA, mRNA
      expression of leptin was measured via real-time PCR. RESULTS: In the
      hyperinsulinemic KK/HlJ mice, hypoxia was not able to further increase the amount
      of leptin in serum. Instead, a significant decrease of insulin levels was
      detected, while serum leptin and insulin levels increased in C57BL/6J. Analysis
      of leptin mRNA expression in subcutaneous fat, mesenteric fat and kidney revealed
      that hypoxia induces leptin transcription in kidneys of C57/BL6 but not in
      hyperinsulinemic animals. In contrast, leptin expression in adipose tissue was
      not increased during hypoxia. DISCUSSION: We conclude that leptin regulation
      during hypoxia in vivo depends at least in part on the modulating role of
      insulin. The hypoxia driven induction of insulin expression in C57/BL6 animals
      may be responsible for the stimulation of leptin transcription. In contrast,
      already hyperinsulinemic animals showed no induction - neither of insulin nor
      leptin after short-term hypoxia.

PMID- 19100294
TI  - Towards an understanding of the mechanism of action of praziquantel.
AB  - Although praziquantel (PZQ) has been used to treat schistosomiasis for over 20
      years its mechanism of action remains unknown. We have developed an assay based
      on the transcriptional response of Schistosoma mansoni PR-1 to heat shock to
      confirm that while 6-week post-infection (p.i.) schistosomes are sensitive to
      PZQ, 4-week p.i. schistosomes are not. Further, we have used this assay to
      demonstrate that in mice this sensitivity develops between days 37 and 40 p.i.
      When PZQ is linked to the fluorophore BODIPY to aid microscopic visualization, it
      appears to enter the cells of intact 4 and 6-week p.i. schistosomes as well as
      mammalian NIH 3T3 cells with ease suggesting that the differential effects of PZQ
      is not based on cell exclusion. A transcriptomal analysis of gene expression
      between 4 and 6 weeks p.i. revealed 607 up-regulated candidate genes whose
      products are potential PZQ targets. A comparison of this gene list with that of
      genes expressed by PZQ sensitive miracidia reduced this target list to 247 genes,
      including a number involved in aerobic metabolism and cytosolic calcium
      regulation. Finally, we also report the effect of an in vitro sub-lethal exposure
      of PZQ on the transcriptome of S. mansoni PR-1. Annotation of genes
      differentially regulated by PZQ exposure suggests that schistosomes may undergo a
      transcriptomic response similar to that observed during oxidative stress.

PMID- 19100296
TI  - Vacuolar functions determine the mode of cell death.
AB  - The yeast vacuole plays a crucial role in cell homeostasis including pH
      regulation and degradation of proteins and organelles. Class C VPS genes code for
      proteins essential for vacuolar and endosomal vesicle fusion, their deletion
      results in the absence of a detectable vacuole. We found that single gene
      deletions of class C VPS genes result in a drastically enhanced sensitivity to
      treatment with acetic acid whereas sensitivity towards H2O2 remains largely
      unaffected. Interestingly acetic acid treatment known as an established inducer
      of yeast apoptosis leads to necrosis in class C VPS deletion strains. Their
      intracellular pH drops from 6.7 to 5.5 after acetic acid treatment, while in wild
      type the pH drops to just 6.3. When the intracellular pH in wild type is lowered
      below pH 5.5 using a higher concentration of acetic acid, the survival rate is
      similarly low as in the class C VPS mutants, however, the death phenotype is
      predominantly apoptotic. Hence, the vacuole not only prevents acetic acid induced
      cell death by buffering the cytosolic pH, but it also has a proapoptotic
      function.

PMID- 19100297
TI  - Correlation between in vivo pharmacokinetics, intratumoral distribution and
      photodynamic efficiency of liposomal mTHPC.
AB  - Foslip is a recently designed third generation photosensitiser based on
      unilamellar dipalmitoylphosphatidylcholine/dipalmitoylphosphatidylglycerol
      (DPPC/DPPG) liposomal formulations of meta-tetra(hydroxyphenyl)chlorine (mTHPC).
      The present study investigates Foslip behaviour and its photodynamic efficiency
      in EMT6 xenografted nude mice at different times following i.v. administration of
      0.3 mg kg(-1) mTHPC in a Foslip formulation. Plasma pharmacokinetics and
      biodistribution were studied by high performance liquid chromatography and were
      described by a three compartments analysis with half-lifes of 0.13, 4.31 and 35.7
      h. The highest tumour to muscle ratios were observed at 6 and 15 h post
      administration. Intratumoral distribution was carried out using two photon
      excitation confocal microscopy. Progressive efflux from the vascular compartment
      was noted in favour of tumour parenchyma, which was almost completed at 15 h. The
      best tumour response was obtained for a drug-light interval of 6 h, interval for
      which mTHPC was present in both endothelial and parenchyma cells. Tumour and
      plasma concentrations however were far below their maximal values. Based on these
      observations, we assume that the presence of mTHPC in both vasculature and tumour
      cells is required for optimal PDT efficacy.

PMID- 19100298
TI  - Dual imaging of pulmonary delivery and gene expression of dry powder inhalant by
      fluorescence and bioluminescence.
AB  - In gene therapy with an inhalant, therapeutic outcome depends on both the
      pulmonary delivery of the agent and the gene expression properties in the lung.
      The aim of the present study was to visualize and evaluate both the pulmonary
      delivery and the gene expression properties of a dry powder at once in mice. We
      used indocyanine green (ICG) as a fluorescent label, the plasmid DNA pCMV-Luc
      encoding the firefly luciferase as a reporter, chitosan as a non-viral vector and
      lactose as a carrier of the dry powder prepared by a supercritical carbon dioxide
      process. The pulmonary delivery of the dry powder and the gene expression in the
      lung were evaluated by detection of fluorescence of ICG and the detection of
      luciferase activity, respectively, by using a real-time in vivo imaging system
      (IVIS imaging system, Xenogen Corporation). The fluorescence and bioluminescence
      were more specifically detected by measuring from the back of the mice. We
      succeeded in visualizing both the pulmonary delivery and the gene expression in
      the same mouse that correlated with each other. In conclusion, the dry powder
      containing both ICG and pCMV-Luc was useful as a dual imaging system to visualize
      pulmonary delivery and gene expression in mice.

PMID- 19100299
TI  - Enhanced generation of cytotoxic T lymphocytes by increased cytosolic delivery of
      MHC class I epitope fused to mouse heat shock protein 70 via polyhistidine
      conjugation.
AB  - Heat shock protein 70 (Hsp70)-associated antigens in a soluble form have been
      shown to elicit strong antigen-specific cytotoxic T lymphocyte (CTL) responses
      following immunization without any adjuvants. In order to improve the potential
      of Hsp70, we genetically designed a novel Hsp70-based antigen delivery system, in
      which the model MHC class I epitope of ovalbumin (OVA) (SIINFEKL; OVA257-264) was
      fused to mouse Hsp70. To facilitate the cytosolic delivery of the peptide
      following Hsp receptor-mediated endocytosis, polyhistidine of 25 or 50 residues
      was further fused to the fusion protein. Each fusion protein was then expressed
      in E. coli and purified. When added to DC2.4 cells, a mouse dendritic cell line,
      the fusion protein containing polyhistidine of 25 residues was efficiently taken
      up by the cells and efficiently distributed to the cytosol. The fusion protein
      also exhibited a significantly improved efficacy of MHC class I-restricted
      presentation of antigen. Vaccination of mice with the polyhistidine fusion
      protein generated strong antigen-specific CTL responses and antitumor activity.
      These findings suggest that polyhistidine fusion is a useful strategy to increase
      the potential of Hsp-based vaccination.

PMID- 19100300
TI  - Pharmacogenomics and -genetics in colorectal cancer.
AB  - Despite recent progress in our knowledge about the development and therapy of
      colorectal cancer (CRC), it still remains one of the major cancer related deaths
      throughout the world. With the introduction of new cytotoxic and targeting agents
      a significant improvement in progression-free and overall survival has been
      achieved. However, a significant percentage (40-50%) of patients do not
      experience beneficial effects and suffer from severe toxicities. It will be
      critical to identify molecular markers, which may help to assess therapeutic
      response and outcome in CRC. Validation of predictive and prognostic molecular
      markers will enable oncologists to tailor patient specific treatment strategies
      for the individual patient according to the molecular profile of both the patient
      and their tumor. Individualized therapy will help to improve therapeutic efficacy
      and to minimize toxicities and therapeutic expenses.

PMID- 19100301
TI  - Eating style, overeating, and overweight in a representative Dutch sample. Does
      external eating play a role?
AB  - This study examined which individuals in particular are susceptible or resistant
      to develop overweight in our current obesogenic environment. A cross-sectional
      study was conducted in a sample of 1342 people representative of the general
      population in the Netherlands. Overweight-level (normal body weight> or =17.5 BMI
      [weight in kilograms/height in meters squared, as self-reported] <25) versus
      overweight ((BMI> or =25)) and overeating, as measured by questionnaire, were
      assessed in relation to dietary restraint, emotional eating and external eating,
      as assessed with the Dutch Eating Behaviour Questionnaire. Both dietary restraint
      and emotional eating moderated the relationship between overconsumption and
      overweight, but that there was no (positive) main effect or moderator effect for
      external eating. It was concluded that dietary restraint may prevent people who
      overeat from getting overweight. An individual's final level of body weight may
      possibly be determined more by people's tendency toward emotional eating than by
      people's sensitivity to environmental food cues.

PMID- 19100302
TI  - Vaccination with combination of Fit3L and RANTES in a DNA prime-protein boost
      regimen elicits strong cell-mediated immunity and antitumor effect.
AB  - With accumulating evidence indicating the importance of cytotoxic T lymphocytes
      (CTLs) in the antitumor response, strategies are being pursued to elicit
      augmented CD8(+) T-cell responses against tumors with tumor vaccines. Here, we
      report the protective efficacy of vaccine-elicited antitumor immune responses
      with an aggressive HBc-expressing B16-HBc melanoma, which expressed HBc as a self
      and model antigen, tumor model. We demonstrated that the significantly better
      memory responses or marked inhibition on tumor growth could be achieved after
      coadministration of cytokine adjuvants RANTES and Flt3L in a DNA prime-protein
      boost regimen. Furthermore, the augmentation of DNA prime-protein boost regimens
      by cytokines gene was due to the improvement the immunopotency of DNA vaccine and
      subsequently the augmented Ag-specific and IFN-gamma mediating CD8(+) T-cell
      responses after protein boosting. Hence, this study demonstrates for the first
      time that combinatorial use of chemotactic and potent DC-specific growth factor
      molecules provides a useful strategy for enhancing antitumor responses.

PMID- 19100303
TI  - Differential immunogenicity of Vibrio cholerae O139 variants expressing different
      combinations of naturally occurring and atypical forms of the serogroup
      polysaccharide.
AB  - Field testing of an inactivated bivalent O1/O139 cholera vaccine suggests that
      Vibrio cholerae O1 is more immunogenic than V. cholerae O139. To investigate
      whether this might be partly attributable to the production of capsular
      polysaccharide (CPS) by O139 isolates, we have compared the immunogenicity of
      variant strains expressing different combinations of lipopolysaccharide (LPS) and
      CPS. These studies indicate that the core-linked LPS structure is of paramount
      importance for induction of antibodies to the serogroup antigen. By contrast CPS
      was minimally immunogenic. Significantly the presence of CPS did not modulate the
      immunogenicity of the underlying LPS. To examine whether differences in LPS
      structure might contribute to the differing immunogenicities of the O1 and O139
      serogroups, an attempt was made to modify the normal O139 LPS structure by
      provision of one of several heterologous wzz genes. The resulting variants
      displayed additional, atypical surface polysaccharide, whose modal length was
      characteristic for the particular wzz gene. By immunoblotting this novel material
      showed a ladder-like banding pattern typical of LPS, but its failure to be
      stained by silver indicated that it was not core-associated and was therefore
      more like truncated CPS. Consistent with our earlier findings, studies using
      systemic or mucosal routes of immunization failed to demonstrate any consistent
      enhancement of antibody responses associated with production of these aberrant
      polysaccharide polymers.

PMID- 19100304
TI  - Immunological responses to pneumococcal vaccine in frail older people.
AB  - Advanced age has been associated with a wide range of defects in both the innate
      and adaptive immune systems including diminished specific antibody responses that
      increase the risk of invasive pneumococcal disease (IPD) and limit the
      effectiveness of vaccines. However, the elderly are a heterogeneous group and
      measures of overall frailty may be a better indicator of disease susceptibility
      (or vaccine response) than chronological age alone. AIM: To evaluate the
      immunogenicity of the 7-valent conjugated pneumococcal vaccine (PCV7) versus 23
      valent polysaccharide vaccine (23vPPV) and compare the immune response to four
      serotypes (4, 6B, 18C and 19F), with respect to age or frailty in an elderly
      population of previously unvaccinated hospitalized patients. METHOD: 241 patients
      aged 60 years and over, recruited between 16 May 2005 and 20 February 2006, were
      randomised to 23PPV or PCV7 vaccine. We measured Frailty Index (FI), Barthel
      index and the MiniMental State. Serotype-specific IgG was measured by ELISA at
      base line and 6 months after vaccination. Antibody responses were defined by the
      ratio of post-vaccination to pre-vaccination IgG antibody concentration (poor < 2
      fold increase, acceptable > or = 2.0 to 3.99-fold and strong > or = 4.0-fold
      increase). RESULTS: Pre-immunization IgG was generally low and did not differ
      significantly by age or frailty. Post-immunization, IgG increased to all four
      serotypes; acceptable or strong response ranged between 29% for (6B) and 57% for
      (18C). There was no significant difference between the two vaccine types (23PPV
      versus PCV7). At 6 months post-vaccination, the highest geometric mean IgG
      concentrations (GMCs) were seen for serotype 19F and the lowest for serotype 4.
      Although there was some variation by serotype, responses after vaccination were
      lowest in the most frail or aged subjects. CONCLUSIONS: Pneumococcal vaccines are
      perceived to offer low protection in the frail elderly, but our study showed that
      the proportion of this vulnerable population with acceptable responses is
      encouraging. Frailty, as measured by the Frailty Index, appears to be a better
      predictor of immune response to pneumococcal vaccines than age alone.

PMID- 19100305
TI  - Murine models for evaluating the allergenicity of novel proteins and foods.
AB  - Genetically modified crops convey many benefits to world population. However, a
      rigorous safety assessment procedure, including an evaluation of the allergenic
      potential, is fundamental before their release into the food chain. As an
      integral part of the safety assessment process, regulatory authorities worldwide
      strongly recommend the use of tests that can predict the allergenic potential of
      the novel proteins. All guidance documents are based on an array of tests that
      have been proposed in 2003 by the Codex Alimentarius. Although the animal model
      is not a requirement of the Codex Alimentarius weight of evidence approach,
      allergenic hazard of novel proteins could only be evaluated by an in vivo model
      that can potentially identify and distinguish commonly allergenic proteins from
      rarely allergenic proteins. Therefore, food allergy experts encourage its
      development. During the 2007 International Life Science Institute (ILSI) workshop
      (Nice, France), worldwide experts shared their latest research results on rodent
      models to evaluate the allergenic potential of proteins and foods. This review
      presents the most promising rodent models for assessing food protein
      allergenicity that were evaluated during this ILSI workshop.

PMID- 19100306
TI  - Analysis of gene expression changes of drug metabolizing enzymes in the livers of
      F344 rats following oral treatment with kava extract.
AB  - The association of kava product use with liver-related risks has prompted
      regulatory action in many countries. We studied the changes in gene expression of
      drug metabolizing enzymes in the livers of Fischer 344 male rats administered
      kava extract by gavage for 14 weeks. Analysis of 22,226 genes revealed that there
      were 14, 41, 110, 386, and 916 genes significantly changed in the 0.125, 0.25,
      0.5, 1.0, and 2.0 g/kg treatment groups, respectively. There were 16 drug
      metabolizing genes altered in all three high-dose treatment groups, among which
      seven genes belong to cytochrome P450 isozymes. While gene expression of Cyp1a1,
      1a2, 2c6, 3a1, and 3a3 increased; Cyp 2c23 and 2c40 decreased, all in a dose
      dependent manner. Real-time PCR analyses of several genes verified these results.
      Our results indicate that kava extract can significantly modulate drug
      metabolizing enzymes, particularly the CYP isozymes, which could cause herb-drug
      interactions and may potentially lead to hepatotoxicity.

PMID- 19100307
TI  - Inflammation in methotrexate-induced pulmonary toxicity occurs via the p38 MAPK
      pathway.
AB  - Methotrexate (MTX) has been widely used for the treatment of inflammatory
      diseases and rheumatoid arthritis (RA), as well as a variety of tumors. However,
      MTX-induced toxicity is a serious and unpredictable side effect of this therapy
      and an important clinical problem. We used microarray analysis to examine MTX
      induced gene expression in a human lung epithelial cell line (BEAS-2B) and
      identified 10 differentially expressed genes related to the p38 mitogen-activated
      protein kinase (MAPK) pathway, including IL-1beta, MKK6, and MAPKAPK2.
      Differential gene expression was confirmed via real-time RT-PCR. To determine the
      functional significance of MTX-induced p38 MAPK activation, we used a p38 MAPK
      inhibitor (SB203580) to block the p38 MAPK cascade. We also used protein array
      technology to investigate the modulated expression of pro- and anti-inflammatory
      cytokines in BEAS-2B cells. MTX activated IL-1beta expression and induced the
      phosphorylation of various proteins in the p38 MAPK cascade, including TAK1,
      MKK3/MKK6, p38 MAPK, MAPKAPK2, and HSP27. Finally, HSP27 activation may increase
      IL-8 secretion, resulting in a pulmonary inflammatory response such as
      pneumonitis. Although IL-1beta and IL-8 expression increased, the expression of
      IL-4, IL-6, IL-12, TNF-alpha, MIP-1alpha, and MIP-1beta decreased in a dose
      dependent manner. These results suggest that the modulation of cytokine
      expression may play an important role in MTX-induced pulmonary toxicity.

PMID- 19100308
TI  - HSD17B4 overexpression, an independent biomarker of poor patient outcome in
      prostate cancer.
AB  - Steroid hormones and their metabolising enzymes have been studied extensively for
      their potential role in prostate cancer, with more recent interest in the
      androgen/estrogen inactivating enzyme 17beta-hydroxysteroid dehydrogenase type 4
      (HSD17B4). Gene expression profiling showed HSD17B4 to be significantly
      overexpressed in prostate cancer compared to matched-benign epithelium. We
      therefore hypothesized that altered HSD17B4 expression may contribute to prostate
      cancer progression via altered hormone balance. In this study, HSD17B4 mRNA and
      protein expression were assessed by in situ hybridisation (ISH) and
      immunohistochemistry (IHC), respectively, in tissue arrays of prostate tissue
      from 172 patients treated by radical prostatectomy. Overexpression of HSD17B4
      mRNA and protein was associated with prostate cancer (P<0.0001) and multivariate
      Cox proportional hazards analysis, adjusted for known prognostic indicators,
      demonstrated HSD17B4 mRNA and high protein expression were significant
      independent predictors of poor patient outcome as measured by time until PSA
      relapse (mRNA: hazards ratio [HR]=1.90, 95% confidence interval [CI]=1.15-3.12;
      P<0.0001; and protein: HR=2.09, 95% CI=1.31-3.33; P=0.0026). Here we provide
      strong evidence that both mRNA and protein overexpression of HSD17B4 is not only
      associated with the presence of prostate cancer, but is also a significant
      independent predictor of poor patient outcome.

PMID- 19100309
TI  - Betacellulin overexpression in transgenic mice improves glucose tolerance and
      enhances insulin secretion by isolated islets in vitro.
AB  - Betacellulin (BTC), a ligand of the epidermal growth factor receptor, has been
      shown to promote growth and differentiation of pancreatic beta-cells and to
      improve glucose metabolism in experimental diabetic rodent models. We employed
      transgenic mice (BTC-tg) to investigate the effects of long-term BTC
      overabundance on islet structure and glucose metabolism. Expression of BTC is
      increased in transgenic islets, which show normal structure and distribution of
      the different endocrine cell types, without pathological alterations. BTC-tg mice
      exhibit lower fasted glucose levels and improved glucose tolerance associated
      with increased glucose-induced insulin secretion. Surprisingly, quantitative
      stereological analyses revealed that, in spite of increased cell proliferation,
      the islet and beta-cell volumes were unchanged in BTC-tg mice, suggesting
      enhanced cell turnover. Insulin secretion in vitro was significantly higher in
      transgenic islets in medium containing high glucose (11.2 or 16.7mM) as compared
      to control islets. Our results demonstrate that long-term BTC overabundance does
      not alter pancreatic islet structure and beta-cell mass, but enhances glucose
      induced insulin secretion in vivo as well as in vitro.

PMID- 19100310
TI  - Secretion and uptake of TAT-fusion proteins produced by engineered mammalian
      cells.
AB  - BACKGROUND: Intracellular signaling can be regulated by the exogenous addition of
      physiological protein inhibitors coupled to the TAT protein transduction domain.
      Thus far experiments have been performed with purified inhibitors added
      exogenously to cells in vitro or administered in vivo. Production of secretable
      TAT-fusion proteins by engineered mammalian cells, their uptake, and route of
      entry has not been thoroughly investigated. Such methodology, if established,
      could be useful for transplantation purposes. METHODS: Secretion of TAT-fusion
      proteins from transfected mammalian cells was achieved by means of a signal
      peptide. Cell uptake and subcellular localization of TAT-fusion proteins were
      determined by immunoblotting and confocal microscopy. RESULTS: Engineered TAT
      fusion proteins were secreted with variable efficiency depending on the nature of
      the protein fused to the TAT peptide. Secreted proteins were able to transduce
      unmanipulated cells. Their mechanism of entry into cells partly involves lipid
      rafts and a portion of the internalised protein is directed to the Golgi.
      CONCLUSIONS: Generation of secretable TAT-coupled inhibitors of signaling
      pathways, able to transduce other cells can be achieved. GENERAL SIGNIFICANCE:
      These results provide key information that will assist in the design of TAT
      inhibitors and engineered cells in order to regulate cell function within
      tissues.

PMID- 19100311
TI  - Disruption of iron homeostasis and lung disease.
AB  - As a result of a direct exchange with the external environment, the lungs are
      exposed to both iron and agents with a capacity to disrupt the homeostasis of
      this metal (e.g. particles). An increased availability of catalytically reactive
      iron can result from these exposures and, by generating an oxidative stress, this
      metal can contribute to tissue injury. By importing this Fe(3+) into cells for
      storage in a chemically less reactive form, the lower respiratory tract
      demonstrates an ability to mitigate both the oxidative stress presented by iron
      and its potential for tissue injury. This means that detoxification is
      accomplished by chemical reduction to Fe(2+) (e.g. by duodenal cytochrome b and
      other ferrireductases), iron import (e.g. by divalent metal transporter 1 and
      other transporters), and storage in ferritin. The metal can subsequently be
      exported from the cell (e.g. by ferroportin 1) in a less reactive state relative
      to that initially imported. Iron is then transported out of the lung via the
      mucociliary pathway or blood and lymphatic pathways to the reticuloendothelial
      system for long term storage. This coordinated handling of iron in the lung
      appears to be disrupted in several acute diseases on the lung including
      infections, acute respiratory distress syndrome, transfusion-related acute lung
      injury, and ischemia-reperfusion. Exposures to bleomycin, dusts and fibers, and
      paraquat similarly alter iron homeostasis in the lung to affect an oxidative
      stress. Finally, iron homeostasis is disrupted in numerous chronic lung diseases
      including pulmonary alveolar proteinosis, transplantation, cigarette smoking, and
      cystic fibrosis.

PMID- 19100313
TI  - Adaptive evolution of rbcL in Conocephalum (Hepaticae, bryophytes).
AB  - An excess of nonsynonymous substitutions over synonymous ones has been regarded
      as an important indicator of adaptive evolution or positive selection at the
      molecular level. We now report such a case for rbcL sequences among cryptic
      species in Conocephalum (Hepaticae, Bryophytes). This finding can be regarded as
      evidence of adaptive evolution in several cryptic species (especially in F and JN
      types) within the genus. Bryophytes are small land plants with simple morphology.
      We can therefore expect the existence of several biologically distinct units or
      cryptic species within each morphological species. In our previous study, we
      found three rbcL types in Asian Conocephalum japonicum (Thunb.) Grolle and also
      found evidence strongly suggesting that the three types are reproductively
      isolated cryptic species. Additionally, we examined rbcL sequence variation in
      six cryptic species of C. conicum (L.) Dumort. previously recognized by allozyme
      analyses. As a result, we were able to discriminate the six cryptic species based
      only on their rbcL sequences. We were able to show that rbcL sequence variation
      is also useful in finding cryptic species of C. conicum.

PMID- 19100312
TI  - Recognition and reading aloud of kana and kanji word: an fMRI study.
AB  - It has been proposed that different brain regions are recruited for processing
      two Japanese writing systems, namely, kanji (morphograms) and kana
      (syllabograms). However, this difference may depend upon what type of word was
      used and also on what type of task was performed. Using fMRI, we investigated
      brain activation for processing kanji and kana words with similar high
      familiarity in two tasks: word recognition and reading aloud. During both tasks,
      words and non-words were presented side by side, and the subjects were required
      to press a button corresponding to the real word in the word recognition task and
      were required to read aloud the real word in the reading aloud task. Brain
      activations were similar between kanji and kana during reading aloud task,
      whereas during word recognition task in which accurate identification and
      selection were required, kanji relative to kana activated regions of bilateral
      frontal, parietal and occipitotemporal cortices, all of which were related mainly
      to visual word-form analysis and visuospatial attention. Concerning the
      difference of brain activity between two tasks, differential activation was found
      only in the regions associated with task-specific sensorimotor processing for
      kana, whereas visuospatial attention network also showed greater activation
      during word recognition task than during reading aloud task for kanji. We
      conclude that the differences in brain activation between kanji and kana depend
      on the interaction between the script characteristics and the task demands.

PMID- 19100315
TI  - Myosin heavy chain genes expressed in juvenile and adult silver carp
      Hypopthalmichthys molitrix: novel fast-type myosin heavy chain genes of silver
      carp.
AB  - Silver carp Hypopthalmichthys molitrix is eurythermal temperate fish, whose
      muscle is considered to express several types of myosin heavy chain (MYH) genes
      at different stages of its growth and to adjust to the environmental temperature.
      In this study, MYH genes expressed in the muscles of juvenile and adult silver
      carp were investigated. Five types of MYH cDNA clone were isolated from silver
      carp (H. molitrix) by RACE strategy using a set of fast-type MYH specific
      primers, and termed scMYH(F1), scMYH(F2), scMYH(F3), scMYH(F4) and scMYH(F5) in
      the order of their abundance in cDNA libraries constructed from fast skeletal
      muscles of adult silver carp. scMYH(F1), scMYH(F3) and scMYH(F5) showed high
      nucleotide sequence identities of 96, 98 and 96% to gcMYH(F30), gcMYH(F10) and
      gcMYH(FI), respectively, that encode MYHs predominantly expressed in fast
      skeletal muscle of grass carp (Ctenopharyngodon idella) acclimated to 30, 10 and
      20 degrees C, respectively. scMYH(F2) and scMYH(F4) showed a high identity to A4
      type MYH from rock cod (Notothenia coriiceps) slow skeletal muscle. Phylogenetic
      analysis demonstrated that scMYH(F1) and scMYH(F5) were monophyletic with fish
      adult fast-type MYHs, whereas scMYH(F2) and scMYH(F4) formed a cluster with fish
      slow-like fast-type MYH, and scMYH(F3) did with fish embryonic fast-type MYHs.
      Interestingly, juvenile silver carp predominantly expressed scMYH(F3)
      irrespective of acclimation temperatures at 10, 18 or 26 degrees C. The
      comparison among scMYH(F1), scMYH(F2) and scMYH(F3) in the deduced amino acid
      sequence revealed that the putative binding sites for ATP, actin, and essential
      and regulatory light chains in myosin subfragment-1 (S1) have high identities
      with each other (81-100%). However, their loop-1 and loop-2 regions in S1 were
      highly variable, suggesting their different functions. The deduced amino acid
      sequences of myosin subfragment-2 and L-meromyosin showed high identities of 90
      91% and 86-90%, respectively, among the above three scMYHs.

PMID- 19100316
TI  - Evolutionary selection pressure of forkhead domain and functional divergence.
AB  - Forkhead-box (Fox) genes encode a family of transcription factors defined by a
      "winged helix" DNA-binding domain which have been identified in many metazoans,
      and play important roles in diverse biological processes. Here we aimed to extend
      previous evolutionary selection analysis to fungi, using available sequences from
      E. cuniculi (Ec), Eremothecium gossypii (Eg), Saccharomyces cerevisiae (Sc), etc.
      The phylogeny of 335 Fox protein sequences was reconstructed, revealing the
      existence of 26 orthologous groups that were well supported by gene phylogeny
      which arose following a series of gene duplication events. Gene conversion events
      may also play important roles in the evolution of Fox genes. The nonsynonymous to
      synonymous substitution ratios (dN/dS) for orthologous groups suggested that
      after gene duplication and/or speciation of forkhead clusters, rapid
      differentiation and the negative selection have occurred, prompting the formation
      of distinct Fox subclasses and new functions. SDPpred was used to produce a set
      of the alignment positions (specificity determining positions) which is involved
      in conferring differential functional specificity. These findings explained the
      functional divergence of Fox gene family.

PMID- 19100317
TI  - Gene expression analysis of terminal differentiation of human melanoma cells
      highlights global reductions in cell cycle-associated genes.
AB  - Defects in differentiation are frequently observed in cancer cells. By
      appropriate treatment specific tumor cell types can be induced to terminally
      differentiate. Metastatic HO-1 human melanoma cells treated with IFN-beta plus
      mezerein (MEZ) undergo irreversible growth arrest and terminal differentiation
      followed by apoptosis. In order to define the molecular changes associated with
      this process, changes in gene expression were analyzed by cDNA microarray
      hybridization and by semi-quantitative and quantitative RT-PCRs of representative
      44 genes. The expression of 210 genes was changed more than two-fold at either 8
      or 24 h post-treatment (166 up and 44 down). Major biological processes
      associated with the up-regulated genes were response to endogenous/exogenous
      stimuli (38%), cell proliferation (13%), cell death (16%) and development (30%).
      Approximately 34% of the down-regulated genes were associated with cell cycle, 9%
      in DNA replication and 11% in chromosome organization, respectively. Suppression
      of cell cycle associated genes appeared to directly correlate with growth arrest
      observed in the terminal differentiation process. Expression of Calpain 3 (CAPN3)
      variant 6 was suppressed by the combined treatment and maintained high in various
      melanoma cell lines. However, over-expression of the CAPN3 did not significantly
      affect growth kinetics and cell viability, suggesting that up-regulation of CAPN3
      alone may not be a causative, but an associated change with melanoma development.
      This analysis provides further insights into the spectrum of up-regulated and the
      first detailed investigation of down-regulated gene changes associated with and
      potentially causative of induction of loss of proliferative capacity and terminal
      differentiation in human melanoma cells.

PMID- 19100318
TI  - Effects of in utero exposure to nanoparticle-rich diesel exhaust on testicular
      function in immature male rats.
AB  - We investigated the effects of in utero exposure to nanoparticle-rich diesel
      exhaust (NR-DE) on reproductive function in male rats. Pregnant F344 rats were
      exposed to NR-DE (148.86 microg/m(3), 1.83 x 10(6)particles/cm(3), 3.40 ppm CO,
      1.46 ppm NOx), filtered diesel exhaust (F-DE; 3.10 microg/m(3), 2.66
      particles/cm(3), 3.30 ppm CO, 1.41 ppm NOx), or clean air (as a control) from
      gestation days 1 to 19 (gestation day 0=day of sperm-positivity). Male offspring
      were examined on postnatal day 28. The relative weights of the seminal vesicle
      and prostate to body weight were decreased after exposure to NR-DE or F-DE
      compared with controls. Serum concentrations of testosterone, progesterone,
      corticosterone, and follicle stimulating hormone and testicular concentrations of
      steroidogenic acute regulatory protein and 17beta-hydroxysteroid dehydrogenase
      mRNA were decreased after exposure to NR-DE or F-DE compared with control levels.
      In contrast, serum concentrations of immunoreative inhibin were increased after
      exposure to NR-DE or F-DE compared with control levels, whereas transcription of
      follicle stimulating hormone receptor mRNA was increased in the NR-DE exposure
      group only. These results suggest that prenatal exposure to NR-DE or F-DE leads
      to endocrine disruption after birth and suppresses testicular function in male
      rats. Because both the NR-DE and F-DE-exposed groups reacted to the same extent,
      the nanoparticles in DE did not contribute to the observed reproductive toxicity.

PMID- 19100319
TI  - Enhancement of oral bioavailability of an HIV-attachment inhibitor by nanosizing
      and amorphous formulation approaches.
AB  - BMS-488043 is an HIV-attachment inhibitor that exhibited suboptimal oral
      bioavailability upon using conventional dosage forms prepared utilizing
      micronized crystalline drug substance. BMS-488043 is classified as a
      Biopharmaceutics Classification System (BCS) Class-II compound with a poor
      aqueous solubility of 0.04mg/mL and an acceptable permeability of 178nm/s in the
      Caco2 cell-line model. Two strategies were evaluated to potentially enhance the
      oral bioavailability of BMS-488043. The first strategy targeted particle size
      reduction through nanosizing the crystalline drug substance. The second strategy
      aimed at altering the drug's physical form by producing an amorphous drug. Both
      strategies provided an enhancement in oral bioavailability in dogs as compared to
      a conventional formulation containing the micronized crystalline drug substance.
      BMS-488043 oral bioavailability enhancement was approximately 5- and 9-folds for
      nanosizing and amorphous formulation approaches, respectively. The stability of
      the amorphous coprecipitated drug prepared at different compositions of BMS
      488043/polyvinylpyrrolidone (PVP) was evaluated upon exposure to stressed
      stability conditions of temperature and humidity. The drastic effect of exposure
      to humidity on conversion of the amorphous drug to crystalline form was observed.
      Additionally, the dissolution behavior of coprecipitated drug was evaluated under
      discriminatory conditions of different pH values to optimize the BMS-488043/PVP
      composition and produce a stabilized, amorphous BMS-488043/PVP (40/60, w/w) spray
      dried intermediate (SDI), which was formulated into an oral dosage form for
      further development and evaluation.

PMID- 19100320
TI  - Particle size control of poly(dl-lactide-co-glycolide) nanospheres for sterile
      applications.
AB  - Parameters affecting the particle sizes of poly(DL-lactide-co-glycolide) (PLGA)
      nanospheres produced by the Emulsion Solvent Diffusion (ESD) method were
      evaluated in this study, so that suitable PLGA nanospheres could be prepared to
      pass through a membrane filter with 0.2 microm pore size and used as a sterile
      product. Experimental results demonstrated that the particle sizes of PLGA
      nanospheres could be reduced by the following efforts. (1) Increase stirring rate
      of poor solvent. (2) Decrease feed rate of good solvent. (3) Increase poor
      solvent ratio. (4) Increase the temperature of poor solvent. (5) Decrease
      polyvinyl alcohol concentration in poor solvent. (6) Increase ethanol
      concentration in good solvent. (7) Decrease PLGA concentration in good solvent.
      After optimization, PLGA nanospheres with a mean particle size of 102-163 nm and
      the 100-98% of filtration fraction could be produced and passed the bacteria
      challenge tests. This study found PLGA nanospheres can be efficiently prepared as
      a sterile product.

PMID- 19100321
TI  - Investigation of ethnomedicinal claims of some plants used by tribals of Satpuda
      Hills in India.
AB  - The tribals residing in Satpuda hills are illiterate, socio-economically backward
      and still depend on medicinal plants for healthcare and for treatment of various
      diseases. The objective of the present study was to investigate ethnomedicinal
      claims of some distinctive medicinal plants utilized by Pawara tribal in the
      Satpuda hills. Methodology used to investigate ethnomedicinal claims include
      seasonwise field visits, collection of information from tribal medicine men
      (Badwa), patients and elderly person in and around study area. Similar use of
      plants told by minimum three Badwas were taken into consideration and cross
      checked with eight elderly persons having traditional knowledge of plants and two
      to five patients who received treatment from Badwa. Present investigation
      revealed that tribals are regularly using 52 species of plants belonging to 36
      families to cure diseases like skin disorders, burn, diarrhea, jaundice, mouth
      ulcer, fever, joint pain, abdominal pain, migraine, menstrual problems, urinary
      problems, wounds, dog bite, as anthelmintic and abortifacient. The study revealed
      14 new ethnomedicinal uses of plants not reported previously in the literature
      and could help to find out new lead compounds for welfare of mankind under
      present day patent regime. Medicinal plant knowledge gained from tribals would be
      very useful for pharmacognosists and pharmacologists.

PMID- 19100322
TI  - An anti-ulcerogenic flavonol diglucoside from Equisetum palustre L.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: The aerial parts of Eqiusetum palustre L. is used
      to treat peptic ulcer in Karaman, Turkey. AIM OF THE STUDY: The present study was
      undertaken to evaluate the in vivo gastroprotective potential and structure
      elucidation of the active constituent(s) through bioassay-guided fractionation
      procedures by using ethanol (EtOH)-induced ulcerogenesis model in rats. MATERIAL
      AND METHODS: The 80% ethanol extract of the aerial parts was subjected to
      subsequent separation procedures such as solvent-solvent partition and column
      chromatography through bioassay-guided fractionation techniques to isolate the
      active anti-ulcer component(s) by using the EtOH-induced ulcer model in rats. The
      ulcer index was used to evaluate and to calculate the gastroprotection
      percentage. RESULTS: The subextracts, n-butanol and remaining H2O, of Equisetum
      palustre showed potent in vivo gastroprotective activity. Bioassay-guided
      fractionation has revealed that a flavonol diglucoside, was isolated as an active
      constituent from the n-BuOH subextract of Equisetum palustre. Structure
      elucidation by standard spectroscopic techniques (1H NMR, 13C NMR and DEPT, etc.)
      revealed that this compound as kaempferol-3-O-1''-beta-d-glucopyranosyl-3-O-1'''
      beta-D-glucopyranoside, which provided remarkable protection at 250 and 500 mg/kg
      doses (69.5 and 98.5% ulcer inhibition, respectively) against ethanol-induced
      gastric lesions. CONCLUSION: Experimental data confirmed the ethnobotanical usage
      of Equisetum palustre, with scientific evidence, in Turkey. Additionally,
      kaempferol-3-O-1''-beta-D-glucopyranosyl-3-O-1'''-beta-D-glucopyranoside, a known
      compound, was defined as an anti-ulcerogenic compound in the present work for the
      first time.

PMID- 19100323
TI  - Extract of the Chinese herbal formula Huo Luo Xiao Ling Dan inhibited adjuvant
      arthritis in rats.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: The herbal formula Huo Luo Xiao Ling Dan (HLXL)
      and its modifications have been used in traditional Chinese medicine for about
      one hundred years to alleviate pain and inflammation. AIM: To investigate the
      effects of HLXL on complete Freund's adjuvant (CFA)-induced multiple-joint
      arthritis in rats. MATERIALS AND METHODS: Male Lewis rats, 190-210 g, were
      immunized subcutaneously at the base of the tail with 200 microl of heat-killed
      Mycobacterium tuberculosis in mineral oil (5 mg/ml). HLXL (2.30 and 4.60 g/kg) or
      vehicle control (n=8 per group) was administered orally (i.g.) once a day between
      days 16 and 25 post-CFA injection. The rats were observed for signs of arthritis
      with arthritic changes (erythema, edema, induration) being scored on a scale of 0
      4 of increasing severity using a standard scoring system. The maximum arthritis
      score per rat was 16. A plethysmometer was used to measure edema volume in each
      paw. Adverse effects of HLXL were monitored by closely observing the animals for
      unusual behavioral changes. Levels of tumor necrosis factor alpha (TNF-alpha) and
      interleukin-1 beta (IL-1beta) in local tissue were measured by enzyme-linked
      immunosorbent assay on day 25 post-CFA. RESULTS: HLXL significantly decreased
      arthritis scores between days 23-25 in the 2.30 g/kg group and 21-25 in the 4.60
      g/kg group (p<0.05). It reduced paw edema on days 22 and 24 in the 2.30 g/kg
      group and on days 20, 22 and 24 in the 4.60 g/kg group compared to control
      (p<0.05). Local tissue TNF-alpha and IL-1beta levels on day 25 post-CFA injection
      were significantly (p<0.05) lower in rats treated with HLXL than in control rats.
      No observable adverse effects were found. CONCLUSION: The data suggest that HLXL
      produces significant anti-arthritic effects that may be mediated by suppressing
      pro-inflammatory cytokines, and it appears to be safe.

PMID- 19100324
TI  - Porcine brain microvascular endothelial cell-derived interleukin-8 is first
      induced and then degraded by Streptococcus suis.
AB  - Streptococcus suis is a major pathogen of swine, causing mainly meningitis, and
      it also represents an emerging zoonotic agent. We investigated its ability to
      induce the release of pro-inflammatory cytokines and chemokines by porcine brain
      microvascular endothelial cells (PBMEC). We demonstrated that live S. suis
      induced a strong release of interleukin (IL)-6 and IL-8 by PBMEC. We showed that
      the suilysin (hemolysin) was largely responsible for such stimulation, although
      cell wall components also contribute to cell stimulation but to a considerably
      lower extent. Interestingly, IL-8 production by PBMEC became undetectable by
      increasing either the incubation time or bacterial concentration of certain live
      S. suis strains. We further demonstrated that this decrease of IL-8 levels was
      probably linked to the production of a serine protease by S. suis. Our results
      suggest that S. suis can induce an exacerbated release of inflammatory mediators
      by swine endothelial cells that could cause a massive recruitment of leukocytes
      and subsequent blood-brain barrier breakdown facilitating the pathogenesis of S.
      suis-induced meningitis. In addition, S. suis could modulate this response by
      degrading IL-8 which might delay recruitment of S. suis killer-neutrophils to the
      site of inflammation, allowing this pathogen to survive upon its arrival to
      central nervous system.

PMID- 19100325
TI  - Pharmacological profile of a novel H(2)S-releasing aspirin.
AB  - The pharmacological profile of a new, safe, and effective hydrogen sulfide
      (H(2)S)-releasing derivative of aspirin (ACS14) is described. We report the
      synthesis of ACS14, and of its deacetylated metabolite (ACS21), the preliminary
      pharmacokinetics, and its in vivo metabolism, with the H(2)S plasma levels after
      intravenous administration in the rat. ACS14 maintains the thromboxane
      suppressing activity of the parent compound, but seems to spare the gastric
      mucosa, by affecting redox imbalance through increased H(2)S/glutathione
      formation, heme oxygenase-1 promoter activity, and isoprostane suppression.

PMID- 19100326
TI  - Cloning and heterologous transcription of a polyketide synthase gene from the
      lichen Solorina crocea.
AB  - Lichens and most ascomycete fungi produce polyketide secondary metabolites often
      with valuable biological activities. Their biosynthesis is primarily governed by
      large iterative multifunctional type I polyketide synthases. Although there has
      been good progress studying filamentous non-lichenized fungi, there is limited
      information on polyketide biosynthesis in lichens and their mycobionts, due to
      their slow growth, difficulties in establishing pure cultures, and the absence of
      methods for direct genetic manipulation. However, heterologous expression in a
      surrogate host offers an alternative approach for exploring lichen polyketide
      biosynthesis. Here, we report cloning of a type I polyketide synthase gene from
      the foliose lichen Solorina crocea and its heterologous transcription in the
      filamentous fungus Aspergillus oryzae, including processing of the transcript. No
      new polyketide product was detected. The lichen polyketide synthase showed
      greatest homology with uncharacterized genes from filamentous fungi and lower
      homology with proteins catalysing biosynthesis of the decaketide alternapyrone
      and the tetraketide side-chain of squalestatin. The technology platform utilized
      here presents a useful tool for functional characterization of fungal
      biosynthetic genes and provides a means for novel production of valuable
      compounds.

PMID- 19100327
TI  - Dimethyl sulfoxide (DMSO) produces widespread apoptosis in the developing central
      nervous system.
AB  - Dimethyl sulfoxide (DMSO) is a solvent that is routinely used as a
      cryopreservative in allogous bone marrow and organ transplantation. We exposed
      C57Bl/6 mice of varying postnatal ages (P0-P30) to DMSO in order to study whether
      DMSO could produce apoptotic degeneration in the developing CNS. DMSO produced
      widespread apoptosis in the developing mouse brain at all ages tested. Damage was
      greatest at P7. Significant elevations above the background rate of apoptosis
      occurred at the lowest dose tested, 0.3 ml/kg. In an in vitro rat hippocampal
      culture preparation, DMSO produced neuronal loss at concentrations of 0.5% and
      1.0%. The ability of DMSO to damage neurons in dissociated cultures indicates
      that the toxicity likely results from a direct cellular effect. Because children,
      who undergo bone marrow transplantation, are routinely exposed to DMSO at doses
      higher than 0.3 ml/kg, there is concern that DMSO might be producing similar
      damage in human children.

PMID- 19100328
TI  - Heterologous expression, purification, and characterization of cytochrome P450sca
      2 and mutants with improved solubility in Escherichia coli.
AB  - Pravastatin, an important cholesterol lowering drug, is currently produced by
      hydroxylation of mevastatin (ML-236B) with Streptomyces carbophilus, in which the
      enzyme P450sca-2 plays a key role. Little information on the recombinant
      expression of this enzyme is available. As it is of industrial interest to
      develop an alternative simplified enzymatic process for pravastatin, as a first
      step, further study on the heterologous expression of this enzyme is warranted.
      We report here, for the first time, the purification, and characterization of
      P450sca-2 expressed in Escherichia coli. A synthetic gene encoding P450sca-2 was
      designed to suit the standard codon usage of E. coli. Expression of P450sca-2 in
      E. coli under optimized conditions yielded about 100 nmol purified active P450sca
      2 per liter. Directed evolution was further carried out to improve the soluble
      expression level. In the absence of a facile and sensitive assay, green
      fluorescent protein (GFP) was used as a reporter to enable high-throughput
      screening. After three rounds of evolution by error-prone PCR and DNA shuffling,
      six almost totally soluble mutants were obtained, with the soluble expression
      levels dramatically improved by about 30-fold. For six most frequently occurring
      mutations, the corresponding single mutants were created to dissect the effects
      of these mutations. A single mutation, P159A, was found to be responsible for
      most of the enhanced solubility observed in the six mutants, and the
      corresponding single mutant also retained the hydroxylation activity. Our study
      provides a foundation for future work on improving functional expression of
      P450sca-2 in E. coli.

PMID- 19100329
TI  - Neural substrates of explicit and implicit fear memory.
AB  - Distinct aspects of our fearful experiences appear to be mediated by separate
      explicit and implicit memory processes. To identify brain regions that support
      these separate memory processes, we measured contingency awareness, conditional
      fear expression, and functional magnetic resonance imaging signal during a
      Pavlovian fear conditioning procedure in which tones that predicted an aversive
      event were presented at supra and sub-threshold volumes. Contingency awareness
      developed in conjunction with learning-related hippocampal and parahippocampal
      activity on perceived conditioning trials only. In contrast, conditional fear and
      differential amygdala activity developed on both perceived and unperceived
      trials, regardless of whether contingency awareness was expressed. These findings
      demonstrate the distinct roles of these brain regions in explicit and implicit
      fear memory processes.

PMID- 19100330
TI  - Effect of modified MRS medium on production and purification of antimicrobial
      peptide ST4SA produced by Enterococcus mundtii.
AB  - Highest antimicrobial activity of peptide ST4SA (51,200 AU/mL) was recorded after
      14 h of growth in MRS broth with optimal production at pH 6.0 or 6.5. Growth of
      strain ST4SA in the presence of tryptone, yeast extract, or a combination of the
      two, yielded 102,400 AU/mL. An increase in production of peptide ST4SA to 102,400
      AU/mL was recorded in the presence of 20.0 g/L fructose, but decreased to 25,600
      AU/mL in the presence of lactose (20.0 g/L) or mannose (20.0 g/L) as sole carbon
      source. Lower activity (25,600 AU/mL) was recorded when 2.0 g/L K(2)HPO(4) was
      replaced by 2.0 g/L KH(2)PO(4) in MRS broth. An increase of K(2)HPO(4) to 10.0
      g/L and 20.0g/L resulted in higher activity (102,400 AU/mL). Addition of glycerol
      to MRS broth had a negative effect on peptide ST4SA production. Production of
      peptide ST4SA required the presence of magnesium sulphate, manganese sulphate and
      5.0 g/L sodium acetate. Exclusion of tri-ammonium citrate from the medium
      resulted in reduction of activity to 3,200 AU/mL. Maximum activity (102,400
      AU/mL) was recorded in MRS supplemented with 1.0 ppm Vit. C, DL-6,8-thioctic acid
      or thiamine, respectively. Growth of Listeria ivanovii susbp. ivanovii ATCC 19119
      in the presence of peptide ST4SA (12,800 AU/mL) resulted in 99% cell lysis after
      18 h. Improved production of peptide ST4SA was recorded in MRS broth (Biolab) pre
      treated with Amberlite XAD-1180. Precipitation with ammonium sulphate, followed
      by gel filtration chromatography, yielded the highest level of peptide ST4SA.
      This paper describes the partially deproteination of growth medium to facilitate
      peptide ST4SA purification.

PMID- 19100331
TI  - The urge-to-cough and cough motor response modulation by the central effects of
      nicotine.
AB  - The urge-to-cough is a respiratory sensation that precedes the cough motor
      response. Since affective state modulates the perception of respiratory
      sensations such as dyspnoea, we wanted to test whether nicotine, an anxiolytic,
      would modulate the urge-to-cough and hence, the cough motor response. We
      hypothesized that withdrawal from and administration of nicotine in smoking
      subjects would modulate their anxiety levels, urge-to-cough and cough motor
      response to capsaicin stimulation. Twenty smoking (SM) adults (8F, 12M; 22+/-3
      years; 2.9+/-2.0 pack years) and matched non-smoking (NS) controls (22+/-2 years)
      were presented with randomized concentrations of capsaicin (0-200 microM) before
      and after nicotine (SM only) gum and/or placebo (SM and NS) gum. Subjects rated
      their urge-to-cough using a Borg scale at the end of each capsaicin presentation.
      Cough number and cough motor pattern were determined from airflow tracings.
      Subjects completed State-Trait Anxiety Inventory (STAI) questionnaires before and
      after gum administration. SM subjects that withdrew from cigarette smoking for 12
      h exhibited an increase in anxiety scores, a greater number of coughs and higher
      urge-to-cough ratings compared to NS subjects. Administration of nicotine gum
      reduced anxiety scores, cough number and urge-to-cough ratings to match the NS
      subjects. There was no effect of placebo gum on any of the measured parameters in
      the SM and NS groups. The results from this study suggest that modulation of the
      central neural state with nicotine withdrawal and administration in young smoking
      adults is associated with a change in anxiety levels which in turn modulates the
      perceptual and motor response to irritant cough stimulants.

PMID- 19100332
TI  - Thermal plasticity of mitochondria: a latitudinal comparison between Southern
      Ocean molluscs.
AB  - Mitochondrial volume density (Vv((mt,f))), cristae surface density (Sv((im,mt))),
      cristae surface area (Sv((im,f))) and citrate synthase (CS) activity were
      analysed as indicators of thermal acclimation in foot muscle of the limpet,
      Nacella concinna, and the clam, Laternula elliptica, collected from 4 locations
      within the Southern Ocean, South Georgia (54 degrees S, N. concinna only), Signy
      (60 degrees S), Jubany (L. elliptica only -62 degrees S) and Rothera (67 degrees
      S). Animals were acclimated to 0.0 degrees C whilst a sub-set of N. concinna
      (South Georgia, Signy and Rothera) and L. elliptica (Rothera) were acclimated to
      3.0 degrees C. At 0.0 degrees C N. concinna had higher Vv((mt,f)), Sv((im,mt)),
      Sv((im,f)) and muscle fibre specific CS activity than L. elliptica which
      correlated with the more active life style of N. concinna. However, mitochondrial
      density was very low, 1-2% in both species, suggesting that low temperature
      compensation of mitochondrial density is not a universal evolutionary response of
      Antarctic marine ectotherms. Both Sv((im,mt)) and Sv((im,f)) were reduced by warm
      acclimation of N. concinna. South Georgia N. concinna maintained muscle fibre
      specific CS activity after acclimation, in contrast to N. concinna from Rothera
      and Signy and L. elliptica from Rothera, indicating that they have the
      physiological plasticity to respond to their warmer, more variable thermal
      environment.

PMID- 19100333
TI  - Na,K-ATPase activity and epithelial interfaces in gills of the freshwater shrimp
      Macrobrachium amazonicum (Decapoda, Palaemonidae).
AB  - Diadromous freshwater shrimps are exposed to brackish water both as an obligatory
      part of their larval life cycle and during adult reproductive migration; their
      well-developed osmoregulatory ability is crucial to survival in such habitats.
      This study examines gill microsomal Na,K-ATPase (K-phosphatase activity) kinetics
      and protein profiles in the freshwater shrimp Macrobrachium amazonicum when in
      fresh water and after 10-days of acclimation to brackish water (21 per thousand
      salinity), as well as potential routes of Na+ uptake across the gill epithelium
      in fresh water. On acclimation, K-phosphatase activity decreases 2.5-fold, Na,K
      ATPase alpha-subunit expression declines, total protein expression pattern is
      markedly altered, and enzyme activity becomes redistributed into different
      density membrane fractions, possibly reflecting altered vesicle trafficking
      between the plasma membrane and intracellular compartments. Ultrastructural
      analysis reveals an intimately coupled pillar cell-septal cell architecture and
      shows that the cell membrane interfaces between the external medium and the
      hemolymph are greatly augmented by apical pillar cell evaginations and septal
      cell invaginations, respectively. These findings are discussed regarding the
      putative movement of Na+ across the pillar cell interfaces and into the hemolymph
      via the septal cells, powered by the Na,K-ATPase located in their invaginations.

PMID- 19100334
TI  - High energy phosphate concentrations and AMPK phosphorylation in skeletal muscle
      from mice with inherited differences in hypoxic exercise tolerance.
AB  - The effect of chronic hypobaric hypoxia (1/2 atmospheric pressure) on high energy
      phosphate (HEP) compounds was investigated in slow (soleus; SOL) and fast twitch
      (extensor digitorum longus; EDL) muscle from 3 strains of mice with large
      differences in hypoxic exercise tolerance (HET). Phosphocreatine concentration
      ([PCr]) decreased 16-29% following hypoxia in EDL and SOL in all strains, while
      [ADP] and [AMP] increased. In the EDL, HET was negatively correlated with the
      PCr/ATP ratio and positively correlated with the ATP/P(i) ratio. The free energy
      of ATP hydrolysis (DeltaG(obs)) remained constant despite the substantial changes
      that occurred in HEP profiles. The alteration of HEP set points and preservation
      of DeltaG(obs) are consistent with the notion that (1) maximal rates of steady
      state ATP turnover are reduced under hypoxia, and (2) HEP perturbations during
      rest to work transitions are reduced in skeletal muscle from hypoxia acclimated
      animals. We therefore expected a lower phosphorylation ratio of AMP-activated
      protein kinase (AMPK-P/AMPK) during stimulation in hypoxic acclimated animals.
      However, neither the resting nor stimulated AMPK-P/AMPK was influenced by
      hypoxia, although there were significant differences among strains.

PMID- 19100335
TI  - Occurrence of a novel acetylated amino acid, N(alpha)-acetylhistidine, in
      skeletal muscle of freshwater fish and other ectothermic vertebrates.
AB  - The occurrence of N(alpha)-acetylhistidine (NAH) in skeletal muscle of 91 species
      of freshwater fish and 9 species of other ectothermic vertebrates was
      investigated, with consideration of phylogenetic relationships. Of the 91
      freshwater fish species examined, 13 species (7 cichlids, 5 anabantids, and 1
      catfish) contained considerable amounts (>1 micromol/g) of NAH in their skeletal
      muscles. The highest level (10.37 micromol/g) of NAH was found in the tissue of
      Betta splendens (Siamese fighting fish). Moreover, the NAH contents in the
      tissues of Trichogaster trichopterus (three spot gourami), Kryptopterus bicirrhis
      (glass catfish), Oreochromis niloticus (Nile tilapia), Mikrogeophagus ramirezi
      (ram cichlid) and Parachromis managuensis (Guapote tigre) were 3.17-6.16
      micromol/g. The skeletal muscle of amphibians (5 species) and reptiles (4
      species) had a low level (<0.25 micromol/g) of NAH. The present findings clearly
      demonstrate NAH as the fifth imidazole-related compound, in addition to
      histidine, carnosine, anserine and ophidine (balenine), recognized as a major non
      protein nitrogenous constituent in the skeletal muscle of vertebrate animals.

PMID- 19100337
TI  - The future of drug safety testing: expanding the view and narrowing the focus.
AB  - Drug safety remains a high profile issue at a time when the cost and time
      required to develop a new drug are at an all time high. Balancing risk against
      the expected clinical benefit is the primary purpose of preclinical and clinical
      testing. We offer an expanded view on the application of predictive strategies
      and technologies to early safety decisions and suggestions to narrow the focus
      for improving preclinical safety testing to the problems that contribute most to
      adverse drug reactions.

PMID- 19100338
TI  - Seizure propagation in a patient with musicogenic epilepsy.
AB  - Musicogenic epilepsy (ME) is a condition in which seizures are triggered by
      music. We describe a novel investigation of the mechanisms of ME using
      noninvasive (ictal 2-flurodeoxyglucose (2-FDG) positron emission tomography
      (PET)) and invasive (subdural arrays and depth electrodes) methodology in one
      patient with ME. Ictal PET defined onsets in the right mesial temporal lobe. This
      was confirmed by intracranial electrode recordings, where there was onset in the
      right mesial temporal lobe, followed by sequential spread to the lateral temporal
      cortex, Heschel's gyrus, insula, and frontal lobes. Right temporal lobectomy
      resulted in Engel class 1 outcome.

PMID- 19100336
TI  - Protein structure prediction and model quality assessment.
AB  - Protein structures have proven to be a crucial piece of information for
      biomedical research. Of the millions of currently sequenced proteins only a small
      fraction is experimentally solved for structure and the only feasible way to
      bridge the gap between sequence and structure data is computational modeling.
      Half a century has passed since it was shown that the amino acid sequence of a
      protein determines its shape, but a method to translate the sequence code
      reliably into the 3D structure still remains to be developed. This review
      summarizes modern protein structure prediction techniques with the emphasis on
      comparative modeling, and describes the recent advances in methods for
      theoretical model quality assessment.

PMID- 19100339
TI  - Curcumin protects against electrobehavioral progression of seizures in the iron
      induced experimental model of epileptogenesis.
AB  - The purpose of the study was to investigate whether dietary intake of curcumin
      can inhibit the onset and progression of seizures and their associated
      pathophysiology in experimental FeCl(3)-induced epileptogenesis. Curcumin was
      considered for this study because it can cross the blood-brain barrier and bind
      redox-active metal ions. It is also well known for its antioxidative, anticancer,
      and anti-inflammatory properties. In the present study, seizures were induced by
      intracortical injection of FeCl(3) into young rats. Synchronized video/EEG
      recordings were obtained to diagnose the progression of seizures. Short-term
      treatment with a curcumin-supplemented diet (1500 pp mw/w) significantly
      inhibited the onset of grade III and IV seizures in rats with iron-induced
      epilepsy. The lower dose of curcumin (500 ppm) was not effective in inhibiting
      grade III seizures, but retarded the onset and progression of generalized
      seizures. The seizure-suppressing potential of curcumin is explained by the
      observed biochemical, behavioral, and ultrastructural results. Our results
      indicate that curcumin significantly prevents generalization of electroclinical
      seizure activity as well as the pathogenesis associated with iron-induced
      epileptogenesis.

PMID- 19100340
TI  - Quantitative and trajectory analysis of movement trajectories in supplementary
      motor area seizures of frontal lobe epilepsy.
AB  - The objectives of this study were to quantitatively analyze the movement
      trajectories of four types of supplementary motor area (SMA) seizures
      (hyperkinetic, tonic posturing, fencing posture, tonic head turning), and to
      compare the movement trajectories of SMA seizures with those of temporal lobe
      seizures and psychogenic nonepileptic seizures. Ten video/EEG recordings of each
      type of seizure were obtained. Imaging data collected by video/EEG monitoring
      were transformed into a digital matrix with image processing software and then
      transformed into a movement trajectory curve with MATLAB 6.5 software. From these
      movement trajectories, amplitude, frequency, proximal/distal limb amplitude
      ratios, and shoulder/abdominal amplitude ratios measurements were calculated. One
      way ANOVA revealed statistically significant differences in average amplitude, as
      well as proximal/distal limb amplitude ratios, in SMA seizures when compared with
      those of temporal lobe seizures and psychogenic nonepileptic seizures. This study
      proved the feasibility of quantitative analysis of SMA seizures and suggests it
      should be further evaluated for its capability to distinguish different seizure
      semiologies for the diagnosis of epilepsy.

PMID- 19100341
TI  - The effectiveness of preconception counseling to reduce adverse pregnancy outcome
      in women with epilepsy: what's the evidence?
AB  - OBJECTIVE: The purpose of this Cochrane review was to determine the effectiveness
      of delivering preconception counseling interventions to women with epilepsy (WWE)
      as a means of reducing adverse pregnancy outcomes, increasing knowledge, and
      increasing intentions to plan pregnancy. METHODS: Two hundred twenty-five
      citations were retrieved from a systematic search of the Cochrane Library and
      electronic databases: Medline (OVID), Scopus, CINAHL, PsychINFO, and ASSIA, and
      hand searches of relevant epilepsy and obstetric journals. RESULTS: The search
      strategy identified 11 studies for consideration for inclusion. However, none met
      the required criteria for inclusion. CONCLUSIONS: There is no robust evidence to
      inform the content, methods of delivery, or likely effectiveness of preconception
      counseling to improve pregnancy outcomes for WWE and their offspring. The value
      of counseling WWE prior to conception remains uncertain and requires evaluation
      in well-designed studies, appropriately powered to detect changes likely
      associated with both maternal and infant outcomes.

PMID- 19100342
TI  - Understanding the molecular epidemiology of foot-and-mouth-disease virus.
AB  - The use of molecular epidemiology is an important tool in understanding and
      consequently controlling FMDV. In this review I will present basic information
      about the disease, needed to perform molecular epidemiology. I will give a short
      introduction to the history and impact of foot-and-mouth disease, clinical
      picture, infection route, subclinical and persistent infections, general aspects
      of the transmission of FMDV, serotype-specific epidemiological characteristics,
      field epidemiology of FMDV, evolution and molecular epidemiology of FMDV. This is
      followed by two chapters describing the molecular epidemiology of foot-and-mouth
      disease in global surveillance and molecular epidemiology of foot-and-mouth
      disease in outbreak investigation.

PMID- 19100343
TI  - Efficacy and mechanism of action of KHBJ-9B, a new herbal medicine, and its major
      compound triterpenoids in human cartilage culture and in a rabbit model of
      collagenase-induced osteoarthritis.
AB  - KHBJ-9B has been formulated by n-butanol fraction from 2 herbs known to have
      cartilage protection and anti-inflammatory effects. We elected to determine the
      osteoarthritic efficacy and mechanism of KHBJ-9B on human osteoarthritis
      cartilage explants culture and in a rabbit model of collagenase-induced
      osteoarthritis (CIA). The major chemical composition and quantification of KHBJ
      9B was determined by high performance liquid chromatography. The efficacy of KHBJ
      9B and its major compounds on cartilage protective effects such as inhibition of
      GAG release and type II collagen degradation, and their cytotoxicity in IL-1beta
      treated human cartilage culture were examined. The mechanism of action of KHBJ-9B
      and its major compounds were evaluated by measuring inflammatory cytokines (IL
      1beta and TNF-alpha) and matrix proteinases (ADAMTS-4, ADAMTS-5, MMP-1, MMP-13
      and TIMP-3) in IL-1beta-treated human cartilage cultures. Also, the therapeutic
      effect of KHBJ-9B was confirmed using a collagenase-induced osteoarthritis (CIA)
      rabbit model. KHBJ-9B and 3 combined triterpenoids potently inhibited the release
      of proteoglycan and type II collagen in a dose dependent manner without
      cytotoxicity in IL-1beta-treated human cartilage explants culture, whereas its
      single major compounds (betulin, pimaradienoic acid and betulinic acid) and COX-2
      inhibitor (NS398) showed little inhibition even at high concentrations. KHBJ-9B
      and the combination of 3 triterpenoids markedly inhibited the level of IL-1beta
      and TNF-alpha, and down-regulated the level of aggrecanases, ADAMTS-4, ADAMTS-5,
      MMP-1 and MMP-13, and up-regulated TIMP-3 in human cartilage explants culture.
      However, standard compounds and NS398 do not much affect the level of TNF-alpha,
      aggrecanases, and TIMP-3 in cartilage explants culture. In in vivo studies, KHBJ
      9B significantly suppressed the stiffness level and global histologic score.
      Cartilage loss was significantly inhibited in the knee joint in a dose dependent
      manner, and this was associated with the finding that loss of proteoglycan,
      degradation of aggrecan and type II collagen was markedly reduced. These results
      suggest that the effect of KHBJ-9B is bigger than the effects of its single major
      compounds of triterpenoids or celecoxib inhibitors on cartilage protection and
      anti-inflammation in human cartilage and in in vivo model of osteoarthritis, and
      thus has potential for use in osteoarthritis treatment.

PMID- 19100344
TI  - Sublingual immunotherapy reduces soluble HLA-G and HLA-A,-B,-C serum levels in
      patients with allergic rhinitis.
AB  - Allergic rhinitis (AR) is characterized by Th2 polarized immune response. Soluble
      HLA (sHLA) molecules play an immunomodulatory activity. Specific immunotherapy is
      the only causal treatment for AR. So far no study investigated the effect of
      sublingual immunotherapy (SLIT) on sHLA molecules. The aim of the study was to
      evaluate sHLA-G and sHLA-A,-B,-C serum levels in AR patients with pollen allergy
      before and after a pre-seasonal course of SLIT. Forty AR patients with pollen
      allergy were enrolled and they assumed a pre-seasonal SLIT course for 3 months.
      Serum sHLA-G and sHLA-A,-B,-C and IFN-gamma and IL-4 levels were determined by
      ELISA method at baseline and 3 months after the end of the SLIT course. Symptoms
      severity was assessed by a Visual Analogue Scale. Both sHLA-G and sHLA-A,-B,-C
      levels significantly diminished (p<0.0001 for both) after SLIT. Moreover, there
      was a highly significant relationship between the serum levels of these two
      soluble molecules (r=0.84). Significant relationship between symptoms evaluated
      by VAS and change of sHLA molecules was also evidenced (r=0.60 and 0.63). Serum
      cytokines were not affected by SLIT. Therefore, this preliminary study provides
      the first evidence that both sHLA-G and sHLA-A,-B,-C levels are significantly
      reduced by SLIT in AR patients with pollen allergy. Therefore, the clinical
      implication of this study is that these soluble molecules might be interpreted as
      biomarker of response to SLIT.

PMID- 19100345
TI  - Testicular mitochondrial alterations in untreated streptozotocin-induced diabetic
      rats.
AB  - Diabetes-induced complications are associated with mitochondrial dysfunction and
      increasing evidence suggests that diabetes has an adverse effect on male
      reproductive function. The STZ-induced diabetic rat was used as an animal model
      for the type 1 form of the disease with the aim of determining its effects in
      spermatogenesis and testicular mitochondrial function. Several aspects of
      mitochondrial function were measured, including respiratory and electric
      potential function, as well as mitochondrial calcium loading capacity.
      Additionally oxidative stress production, antioxidant levels and possible
      apoptotic alterations were also evaluated. We observed that diabetic animals
      present alterations in spermatogenesis in both the testis and epidydimus.
      However, and surprisingly, the overall results in mitochondrial parameters failed
      to reveal severe testicular mitochondrial dysfunction in diabetic animals, with
      the exception of a decrease in calcium load. Taken together, results suggest that
      in animal models that mimic untreated type 1 diabetes the severe effects of the
      condition on spermatogenesis are not directly mitochondrial-mediated.

PMID- 19100348
TI  - Reduction in proximal femoral strength due to long-duration spaceflight.
AB  - Loss of bone mass is a well-known medical complication of long-duration
      spaceflight. However, we do not know how changes in bone density and geometry
      ultimately combine to affect the strength of the proximal femur as a whole. The
      goal of this study was to quantify the changes in proximal femoral strength that
      result from long-duration spaceflight. Pre-and post-flight CT scan-based patient
      specific finite element models of the left proximal femur of 13 astronauts who
      spent 4.3 to 6.5 months on the International Space Station were generated.
      Loading conditions representing single-limb stance and a fall onto the
      posterolateral aspect of the greater trochanter were modeled, and proximal
      femoral strength (F(FE)) was computed. Mean F(FE) decreased from 18.2 times body
      weight (BW) pre-flight to 15.6 BW post-flight for stance loading and from 3.5 BW
      pre-flight to 3.1 BW post-flight for fall loading. When normalized for flight
      duration, F(FE) under stance and fall loading decreased at mean rates of 2.6%
      (0.6% to 5.0%) per month and 2.0% (0.6% to 3.9%) per month, respectively. These
      values are notably greater than previously reported reductions in DXA total
      femoral bone mineral density (0.4 to 1.8% per month). In some subjects, the
      magnitudes of the reductions in proximal femoral strength were comparable to
      estimated lifetime losses associated with aging. Although average post-flight
      proximal femoral strength is greater than forces expected to occur due to falls
      or normal activities, some subjects have small margins of safety. If proximal
      femoral strength is not recovered, some crew members may be at increased risk for
      age-related hip fractures decades after their missions.

PMID- 19100349
TI  - How I choose a prostaglandin analogue.

PMID- 19100346
TI  - Outer membrane permeability and antibiotic resistance.
AB  - To date most antibiotics are targeted at intracellular processes, and must be
      able to penetrate the bacterial cell envelope. In particular, the outer membrane
      of gram-negative bacteria provides a formidable barrier that must be overcome.
      There are essentially two pathways that antibiotics can take through the outer
      membrane: a lipid-mediated pathway for hydrophobic antibiotics, and general
      diffusion porins for hydrophilic antibiotics. The lipid and protein compositions
      of the outer membrane have a strong impact on the sensitivity of bacteria to many
      types of antibiotics, and drug resistance involving modifications of these
      macromolecules is common. This review will describe the molecular mechanisms for
      permeation of antibiotics through the outer membrane, and the strategies that
      bacteria have deployed to resist antibiotics by modifications of these pathways.

PMID- 19100350
TI  - Pediatric sutured intraocular lenses: trouble waiting to happen.

PMID- 19100351
TI  - Has the polymerase chain reaction come of age for ophthalmology?

PMID- 19100352
TI  - Blue-blocking intraocular lenses: myth or reality?

PMID- 19100353
TI  - Clinical trials - more than an assessment of treatment effect: LXV Edward Jackson
      Memorial Lecture.
AB  - PURPOSE: To review the development of clinical trials and demonstrate their value
      beyond the assessment of the treatment effect. DESIGN: Retrospective literature
      review. METHODS: Retrospective literature review. RESULTS: There has been a rapid
      increase in the number of clinical trials in ophthalmology as assessed by the
      number of ophthalmic publications and the number of ongoing National Eye
      Institute-(NEI) sponsored clinical trials over the last four decades. The public
      health significance of the results of these NEI clinical trials goes beyond the
      demonstration of treatment effects and side effects. From these trials, we learn
      about the clinical course and risk factors of disease, allowing us to better
      determine who and when to treat. Furthermore, the collaboration of investigators,
      as they develop and carry out protocols, facilitates incorporation of new ideas
      into the practice of medicine. CONCLUSIONS: The practice of medicine is
      increasingly dependent on the results of carefully designed clinical trials. The
      determination as to whether a new treatment is safe and effective is important,
      but the additional information we can obtain regarding natural history, risk
      factors, and patient satisfaction adds immeasurably to our ability to care for
      our patients.

PMID- 19100354
TI  - Sneezing reflex associated with intravenous sedation and periocular anesthetic
      injection.

PMID- 19100357
TI  - Authorship policy.

PMID- 19100358
TI  - Interpretation of outer retina appearance in high-resolution optical coherence
      tomography.

PMID- 19100362
TI  - Acute lymphoblastic leukemia: introduction.

PMID- 19100364
TI  - New genetic abnormalities and treatment response in acute lymphoblastic leukemia.
AB  - Numerous genetic abnormalities have been identified in acute lymphoblastic
      leukemia (ALL). Here we review the recurrent abnormalities with emphasis on those
      recently discovered, and discuss their association with chemotherapy resistance
      or sensitivity and with clinical response to therapy. Also, the role of genetic
      abnormalities in leukemogenesis and their potential as therapeutic targets will
      be discussed.

PMID- 19100363
TI  - Global genomic characterization of acute lymphoblastic leukemia.
AB  - A key goal in cancer research is to identify the total complement of genetic and
      epigenetic alterations that contribute to tumorigenesis. We are currently
      witnessing the rapid evolution and convergence of multiple genome-wide platforms
      that are making this goal a reality. Leading this effort are studies of the
      molecular lesions that underlie pediatric acute lymphoblastic leukemia (ALL). The
      recent application of microarray-based analyses of DNA copy number abnormalities
      (CNAs) in pediatric ALL, complemented by transcriptional profiling, resequencing
      and epigenetic approaches, has identified a high frequency of common genetic
      alterations in both B-progenitor and T-lineage ALL. These approaches have
      identified abnormalities in key pathways, including lymphoid differentiation,
      cell cycle regulation, tumor suppression, and drug responsiveness. Moreover, the
      nature and frequency of CNAs differ markedly among ALL genetic subtypes. In this
      article, we review the key findings from the published data on genome-wide
      analyses of ALL and highlight some of the technical aspects of data generation
      and analysis that must be carefully controlled to obtain optimal results.

PMID- 19100365
TI  - Epigenetics of acute lymphocytic leukemia.
AB  - The term epigenetics refers to the study of a number of biochemical modifications
      of chromatin that have an impact on gene expression regulation. Aberrant
      epigenetic lesions, in particular DNA methylation of promoter associated CpG
      islands, are common in acute lymphocytic leukemia (ALL). Recent data from
      multiple laboratories indicate that several hundred genes, involving dozens of
      critical molecular pathways, are epigenetically suppressed in ALL. Because these
      lesions are potentially reversible, the reactivation of these pathways using, for
      instance, hypomethylating agents may have therapeutic potential in this disease.
      Furthermore, the analysis of epigenetic alterations in ALL may allow: (1)
      identification of subsets of patients with poor prognosis when treated with
      conventional therapy; (2) development of new techniques to evaluate minimal
      residual disease; (3) better understanding of the differences between pediatric
      and adult ALL; and (4) new therapeutic interventions by incorporating agents with
      hypomethylating activity to conventional chemotherapeutic programs. In this
      review, we describe the role of epigenetic alterations in ALL from a
      translational perspective.

PMID- 19100366
TI  - Leukemia stem cells and human acute lymphoblastic leukemia.
AB  - Leukemias and other cancers have been proposed to contain a subpopulation of
      cells that display characteristics of stem cells and maintain tumor growth. The
      fact that most anticancer therapy is directed against the bulk of the tumor, and
      possibly spares the cancer stem cells, may lie at the heart of treatment failures
      with conventional modalities. Leukemia stem cells are fairly well described for
      acute myeloid leukemia (AML), but their existence and relevance for acute
      lymphoblastic leukemia (ALL) is less clear. Several reports describe
      subpopulations with primitive phenotypes in clinical ALL samples. However, it has
      also been suggested that the majority of leukemic subfractions can propagate
      leukemia in the appropriate experimental setting, and that their hierarchical
      organization is less strict than in AML. In addition, it is uncertain whether
      cancer stem cells arise from malignant transformation of a tissue-specific stem
      cell, or from committed progenitors or differentiated cells that re-acquire a
      stem cell-like program. In common childhood ALL, current evidence points towards
      the cell of origin being a committed lymphoid progenitor. In this review, we
      highlight recent findings relating to the question of leukemia stem cells in ALL.

PMID- 19100368
TI  - Treatment of childhood acute lymphoblastic leukemia.
AB  - Childhood acute lymphoblastic leukemia (ALL) is the most common malignancy of
      childhood. Studies in ALL have been a model for clinical and basic research
      beyond pediatric hemato-oncology. As a result of sustained and well-organized
      research efforts since the early 1960s, childhood ALL now can be successfully
      treated in about 80% of patients by the application of intensive combination
      chemotherapy regimens, which in specific patient subgroups may need to be
      supplemented with radiation therapy and/or hematopoietic stem cell
      transplantation. Triggered by the observation of specific clinical presenting
      features, biological characteristics, and early treatment response being
      associated with treatment outcome, therapy intensity in contemporary ALL
      protocols is adjusted according to prognostic factors predicting the risk of
      relapse. While the goal of effective therapy for the majority of children with
      ALL has been achieved, significant numbers of patients still die due to recurrent
      disease or the toxicity of treatment. Thus, future research must extend our
      molecular understanding of leukemia and host factors in order to even more
      specifically identify the mechanisms underlying the differences in treatment
      response and outcome, and to finally address the therapeutic needs of the
      individual child.

PMID- 19100369
TI  - Treatment of adult acute lymphoblastic leukemia.
AB  - Treatment results in adult acute lymphoblastic leukemia (ALL) have improved
      considerably in the past decade, with an increase of complete remission rates to
      85% to 90% and overall survival rates to 40% to 50%. Superior chemotherapy and
      supportive care, the integration of stem cell transplantation (SCT) into
      frontline therapy, and optimized risk stratification were important developments.
      Even more impressive is the success of targeted therapies in subgroups of ALL. In
      the formerly most unfavorable subgroup, Philadelphia chromosome (Ph)/BCR-ABL
      positive ALL, survival now ranges from 40% to 50% after incorporating imatinib in
      combination chemotherapy. In mature B-ALL, survival rates increased above 80%
      with the combination of short intensive chemotherapy and rituximab. The
      prerequisite for comprehensive therapy is standardized and rapid diagnosis and
      classification as the basis for treatment stratification. Historically, the major
      aim of original risk stratification was to identify patients with a poor
      prognosis who would benefit from treatment intensification with SCT; currently
      stratification has become more complex. Subgroup-specific approaches include age
      adapted therapy, subgroup-adjusted therapy, targeted therapy, and individualized
      therapy based on the presence of minimal residual disease (MRD).

PMID- 19100367
TI  - Pharmacogenetics in acute lymphoblastic leukemia.
AB  - Progress in the treatment of acute lymphoblastic leukemia (ALL) in children has
      been remarkable, from a disease being lethal four decades ago to current cure
      rates exceeding 80%. This exemplary progress is largely due to the optimization
      of existing treatment modalities rather than the discovery of new antileukemic
      agents. However, despite these high cure rates, the annual number of children
      whose leukemia relapses after their initial therapy remains greater than that of
      new cases of most types of childhood cancers. The aim of pharmacogenetics is to
      develop strategies to personalize treatment and tailor therapy to individual
      patients, with the goal of optimizing efficacy and safety through better
      understanding of human genome variability and its influence on drug response. In
      this review, we summarize recent pharmacogenomic studies related to the treatment
      of pediatric ALL. These studies illustrate the promise of pharmacogenomics to
      further advance the treatment of human cancers, with childhood leukemia serving
      as a paradigm.

PMID- 19100370
TI  - New therapeutic strategies in acute lymphoblastic leukemia.
AB  - While cure rates of over 80% are achieved in contemporary pediatric acute
      lymphoblastic leukemia (ALL) protocols, most adults with ALL succumb to their
      disease, and little progress has been made in the treatment of refractory and
      relapsed ALL. Moreover, the burden of therapy is high in a significant number of
      newly diagnosed patients, and in all those with relapse. Early response to
      therapy measured by minimal residual disease evaluation has proven the single
      most important prognostic factor and is increasingly used in risk stratification.
      However, as the benefit from intensification of frontline therapy becomes
      limiting, it becomes increasingly challenging to rescue patients who fail on
      contemporary risk-adapted protocols. New therapeutic strategies are needed, not
      only in salvage regimens but also in frontline protocols for patients who are at
      high risk of relapse. Current novel approaches include new formulations of
      existing chemotherapeutic agents, new antimetabolites and nucleoside analogs,
      monoclonal antibodies against leukemic-associated antigens, cellular
      immunotherapy, and molecular therapeutics. Some have already been adopted into
      standard regimens, while others remain in early stages of development. This
      review summarizes the current status of these novel therapies as they get
      integrated into ALL regimens.

PMID- 19100373
TI  - Ischemia/reperfusion injury in kidney transplantation: mechanisms and prevention.
AB  - Ischemia has been an inevitable event accompanying kidney transplantation.
      Ischemic changes start with brain death, which is associated with severe
      hemodynamic disturbances: increasing intracranial pressure results in bradycardia
      and decreased cardiac output; the Cushing reflex causes tachycardia and increased
      blood pressure; and after a short period of stabilization, systemic vascular
      resistance declines with hypotension leading to cardiac arrest. Free radical
      mediated injury releases proinflammatory cytokines and activates innate immunity.
      It has been suggested that all of these changes-the early innate response and the
      ischemic tissue damage-play roles in the development of adaptive responses, which
      in turn may lead to an acute font of kidney rejection. Hypothermic kidney storage
      of various durations before transplantation add to ischemic tissue damage. The
      final stage of ischemic injury occurs during reperfusion. Reperfusion injury, the
      effector phase of ischemic injury, develops hours or days after the initial
      insult. Repair and regeneration processes occur together with cellular apoptosis,
      autophagy, and necrosis; the fate of the organ depends on whether cell death or
      regeneration prevails. The whole process has been described as the ischemia
      reperfusion (I-R) injury. It has a profound influence on not only the early but
      also the late function of a transplanted kidney. Prevention of I-R injury should
      be started before organ recovery by donor pretreatment. The organ shortage has
      become one of the most important factors limiting extension of deceased donor
      kidney transplantation worldwide. It has caused increasing use of suboptimal
      deceased donors (high risk, extended criteria [ECD], marginal donors) and
      uncontrolled non-heart-beating (NHBD) donors. Kidneys from such donors are
      exposed to much greater ischemic damage before recovery and show reduced chances
      for proper early as well as long-term function. Storage of kidneys, especially
      those recovered from ECD (or NHBD) donors, should use machine perfusion.

PMID- 19100372
TI  - Minimal residual disease in acute lymphoblastic leukemia.
AB  - In patients with acute lymphoblastic leukemia (ALL), monitoring of minimal
      residual disease (MRD) offers a way to precisely assess early treatment response
      and detect relapse. Established methods to study MRD are flow cytometric
      detection of abnormal immunophenotypes, polymerase chain reaction (PCR)
      amplification of antigen-receptor genes, and PCR amplification of fusion
      transcripts. The strong correlation between MRD levels and risk of relapse in
      childhood ALL is well demonstrated; studies in adult patients also support its
      prognostic value. Hence, results of MRD studies can be used to select treatment
      intensity and duration, and to estimate the optimal timing for hematopoietic stem
      cell transplantation. Practical issues in the implementation of MRD assays in
      clinical studies include determining the most informative time point to study MRD
      and the levels of MRD that will trigger changes in treatment intensity, as well
      as the relative cost and informative power of different methodologies. The
      identification of new markers of leukemia and the use of increasingly refined
      assays should further facilitate routine monitoring of MRD and help to clarify
      the cellular and biologic features of leukemic cells that resist chemotherapy in
      vivo.

PMID- 19100374
TI  - The role of macrophages in xenograft rejection.
AB  - Safe and effective xenotransplantation would provide a valuable answer to many of
      the limitations of allogenic transplantation. Such limitations include scarcity
      of organ supply and morbidity to donors in cases of living-related donor
      transplantation. The main hurdle to the efficacious application of
      xenotransplantation in clinical medicine is the fierce host immune response to
      xenografts. This immune response is embodied in 3 different types of xenograft
      rejection. Both hyperacute rejection and delayed xenograft rejection are mediated
      by natural antibodies and are concerned primarily with whole organ rejection.
      Cellular xenograft rejection (CXR), on the other hand, is concerned with both
      whole organ and CXR and is mediated by innate immunity rather than natural
      antibodies. Macrophages, which are cells of the innate immune system, play a role
      in all 3 types of xenograft rejection (not just CXR). They impart their effects
      both directly and through T-cell activation.

PMID- 19100375
TI  - Notes on the new Israeli organ donation law-2008.
AB  - Israel, like most countries, has a dearth of organ donors with many patients on
      the transplant waiting list. In March 2008, the Organ Transplant law was passed
      in the Israeli Parliament. The law states that a person may not give or receive
      financial rewards for a living or cadaveric organ donation. However, a donor may
      receive compensation for financial losses accrued as a direct result of organ
      donation. It is illegal to broker an illegal transaction between potential donors
      and recipients. An Israeli organization can only support transplants outside of
      Israel if they are performed in accordance with the local law and do not involve
      the sale of organs. Underlying this law is the principle that the sale of organs
      is unethical and the belief that organ donation should be based on altruism.
      Almost immediately, the law was subject to criticism particularly relating to the
      fact that it would not help to increase the number of kidneys, because of the
      lack of significant compensation for donors. It remains to be seen what effect
      the new law will have on living organ donation in Israel.

PMID- 19100371
TI  - Immunotherapy in acute leukemia.
AB  - Recent advances in immunotherapy of cancer may represent a successful example in
      translational research, in which progress in knowledge and technology in
      immunology has led to new strategies of immunotherapy, and even past failures in
      many clinical trials have led to a better understanding of basic cancer
      immunobiology. This article reviews the latest concepts in antitumor immunology
      and its application in the treatment of cancer, with particular focus on acute
      leukemia.

PMID- 19100376
TI  - Comparative study of depression and consent among brain death families in donor
      and nondonor groups from March 2001 to December 2002 in Tehran.
AB  - OBJECTIVE: The aim of this research was to study the relationship between
      depression and organ donation among families of brain death cases. MATERIALS AND
      METHODS: This descriptive, cross-sectional study included a sample of first
      degree relatives of brain death cases: 54 relatives among 27 organ donor families
      and 104 relatives among 58 nonorgan donor families participated in the research
      by the counting method. All families were questioned about their willingness for
      organ donation and at least 3 months had passed from their relative's death to
      the time we performed the research. Data were collected via a demographic
      questionnaire and Beck depression inventory (BDI) with a cutoff point of 16;
      persons with scores over 16 were considered depressed. Data were analyzed using
      descriptive statistics, Student t test, and chi-square test. RESULTS: Depression
      was observed in 20.4% of donor families and 17.3% of nondonor families; there was
      no significant difference between them. There were no significant differences in
      the frequency of depression between parents, spouses, and children of the 2
      groups. The organ donors' relatives reported the effectiveness of organ donation
      to alleviate their grief: 66% completely and 32% partially. CONCLUSION: Organ
      donation does not have a significant effect on the course of grief and later
      depression among relatives of brain death cases.

PMID- 19100377
TI  - Celsior versus Wisconsin solution in pancreas transplantation.
AB  - Celsior solution (CS), which has recently become available, that might
      theoretically offer a new means for improving graft preservation quality. The
      present prospective, randomized study was designed to evaluate the efficacy of CS
      compared with University of Wisconsin (UW) for pancreas allografts. Between
      January 2001 and January 2007, 88 patients underwent pancreatic transplantation,
      including the last 30 consecutive simultaneous pancreas kidney patients who were
      randomly assigned to either CS or UW. There was no case of graft thrombosis in
      either group. There were 2 cases of pancreatitis in the UW group compared with 1
      in the CS group. No case of primary nonfunction occurred in either group. There
      were 2 cases of early duodenal stump fistulae in the CS group that required
      transplantectomy, whereas this complication was not observed in the UW group.
      Relaparotomy in the UW group was required in 3 cases due to infection and treated
      by close drainage that which, progressed to fatal sepsis in 1 patient. In the UW
      group with 6 months of follow-up, there were 12 patients insulin free. In the CS
      group, 6 patients underwent relaparotomy, 3 for transplantectomy and the others
      for intra-abdominal infection, which was fatal in 2 cases. In the CS group with 6
      months of follow-up, there were 10 patients insulin free. Two patients died with
      functioning grafts. These results provided indirect evidence that CS solution is
      at least as safe as UW to mitigate postreperfusion graft edema and pancreatitis,
      as well as graft thrombosis.

PMID- 19100378
TI  - Greater hemodynamic instability with histidine-tryptophan-ketoglutarate solution
      than University of Wisconsin solution during the reperfusion period in living
      donor liver transplantation.
AB  - OBJECTIVE: University of Wisconsin (UW) and histidine-tryptophan-ketoglutarate
      (HTK) solutions are the 2 most commonly used liver preservation solutions. The
      aim of this study was to compare cardiovascular stability, acid-base status, and
      potassium concentrations between patients who received grafts preserved in either
      UW or HTK solution in orthotopic liver transplantation (OLT). PATIENTS AND
      METHODS: In this retrospective study, 87 patients who underwent living donor OLT
      were divided into 2 groups: UW (n = 28) and HTK (n = 59). Group HTK was
      subdivided into group NF-HTK (n = 31; nonflushed before reperfusion) and group F
      HTK (n = 28; flushed before reperfusion). We determined mean arterial pressure
      (MAP) and heart rate every minute for 5 minutes after reperfusion and the maximum
      change in these values and incidence of postreperfusion syndrome (PRS). Body
      temperature, cardiovascular and acid-base parameters, as well as potassium
      concentrations were compared at 5 minutes before and 5 and 30 minutes after
      reperfusion. RESULTS: The maximum decreases in MAP within 5 minutes after
      reperfusion were significantly greater in both the NF-HTK and the F-HTK groups.
      The rate of PRS was significantly greater in the NF-HTK compared with the UW
      group. Flushing with HTK solution decreased the rate of PRS; there was no
      significant difference between the F-HTK and UW groups. All serial changes in
      body temperature, cardiovascular and acid-base parameters, as well as potassium
      concentrations were similar among the 3 groups. CONCLUSIONS: The incidence of PRS
      was greater using HTK compared with UW solution during the reperfusion period.
      Therefore, careful hemodynamic management is advised when using HTK solution.

PMID- 19100379
TI  - Actin cytoskeletal and functional studies of the proximal convoluted tubules
      after preservation.
AB  - BACKGROUND: Proximal tubule cells have specialized apical membranes with
      microvilli that provide an extensive surface area for unidirectional transport of
      solute from lumen to blood. The major structural solute component is F-actin,
      which interacts with transmembrane proteins, including ion transport molecules
      related to normal absorptive and secretory functions. Our study was to evaluate F
      actin and fluid absorption (Jv) in proximal tubules after exposure to
      preservation solutions. METHODS: In vitro microperfusion technique and
      immunohistochemistry analysis. RESULTS: 1. Absorptions were similar in 1- and 24
      hour-preserved tubules, as well as in fresh tubules. The exception was tubules
      for 24 hours in Euro-Collins solution, which did not show absorption, suggesting
      that it was affected. 2. Fluorescence intensity of actin tubules preserved for 1
      hour in both solutions showed similar values to each other and to the control
      group; tubules preserved for 24 hours in both solutions were similar to each
      other, although statistically different than the control group and those
      preserved for 1 hour in Belzer (UW) solution. CONCLUSION: There were differences
      among groups in the distribution of F-actin; Jv values were different for 24-hour
      preservation in each solution, whereas fluorescence intensity was similar in both
      24-hour solutions. Thus, actin cytoskeleton was not responsible for it, because
      24-hour preservation in UW showed Jv results comparable to the control group.

PMID- 19100380
TI  - Ischemic preconditioning improves rat kidney allograft function after
      ischemia/reperfusion injury: the role of tumor necrosis factor-alpha.
AB  - OBJECTIVE: The aim of this study was to investigate the early protection of
      ischemic preconditioning (IPC) and its mechanisms in transplanted rat kidneys.
      MATERIALS AND METHODS: Thirty-six male Sprague-Dawley (SD) rat donors and
      recipients were randomly divided into the following groups: sham-operated group
      (A; n = 6); untreated transplantation group (B; n = 6); and treatment group (C; n
      = 6). Group A was subjected to exploratory laparotomy. Group B received
      orthotopic transplantation. Group C underwent a 15-minute period of ischemia
      followed by a 10-minute reperfusion before orthotopic transplantation. We
      assessed the serum creatinine (SCr), blood urea nitrogen (BUN), and to evaluate
      the degree of kidney graft ischemia/reperfusion injury: tumor necrosis factor
      alpha (TNF-alpha), IkappaB kinase-beta (IKK-beta), and nuclear factor-kappa B (NF
      kappaB) P65 subunit mRNA expressions. RESULTS: The levels of SCr and BUN in
      groups C and B were greater than in the sham-operated group (P < .01), but there
      was no significant difference between the C and B groups at 24 hours after
      transplantation (P > .05). The degree of renal graft tubular injury in group C
      was significantly less compared with group B (P < .01). TNF-alpha transcription
      levels at 24 hours after transplantation were significantly less compared with
      the non-IPC group (P < .01). However, no significant difference was observed in
      IKK-beta mRNA and P65 mRNA expressions between groups C and B (P > .05).
      CONCLUSIONS: A 1-cycle schedule of preconditioning (15 min/10 min) attenuated
      renal graft ischemia/reperfusion injury in the early phase. IPC can improve rat
      kidney allograft function after ischemia/reperfusion injury. The inhibitory
      effects on TNF-alpha and on positive feedback signaling of TNF-alpha/NF-kappaB
      pathways may play important roles in renal graft protection in the early stage.

PMID- 19100381
TI  - Short-term resuscitation of predamaged donor livers by brief machine perfusion:
      the influence of temperature.
AB  - Short-term machine perfusion after liver retrieval from non-heart-beating donors
      has been considered a beneficial means to reverse deleterious priming of the
      predamaged organ. In this study, the possible impact of different temperatures
      during aerobic perfusion was addressed, focusing on liver metabolic functions,
      structural integrity, and vascular activation. Livers retrieved 30 minutes after
      cardiac arrest of male Wistar rats (200-300 g) were preserved with histidine
      tryptophan-ketoglutarate (HTK) solution for 18 hours by simple cold storage (CS)
      or subjected to short-term resuscitation (STR) with oxygenated (pO(2) > 500 mm
      Hg) machine perfusion with HTK at 4 degrees C, 12 degrees C, or 22 degrees C for
      2 hours with subsequent CS for 16 hours at 4 degrees C. Upon reperfusion in a
      normothermic perfusion circuit, STR significantly improved enzyme leakage
      (alanine aminotransferase, glutamate dehydrogenase) and metabolic recovery
      (tissue levels of ATP) providing best values at 12 degrees C or 22 degrees C.
      Moreover, a hugely increased gene expression of the adhesion molecule ICAM-1 as
      well as major histocompatibility complex (MHC) class II antigen was seen after
      CS, but significantly alleviated by STR at 4 degrees C or 12 degrees C. However,
      mRNA for both surface proteins rose significantly after STR at 22 degrees C
      compared with CS. In conclusion, STR by oxygenated perfusion is beneficial to the
      predamaged graft, facilitating later transportation and supervision of the graft
      compared with continuous machine preservation. However, increased perfusion
      temperature should be recommended only up to the limit of 12 degrees C to prevent
      overactivation of surface antigen expression.

PMID- 19100383
TI  - Hepatic ischemia-reperfusion induces insulin resistance via down-regulation
      during the early steps in insulin signaling in rats.
AB  - BACKGROUND: The effects of hepatic ischemia-reperfusion (I/R) on insulin
      signaling remain unclear. We observed changes in insulin secretion and signal
      protein expression during the early steps in insulin signaling after hepatic I/R
      in rats. MATERIALS AND METHODS: Eighty healthy Wistar rats were randomly divided
      into an I/R group and a control (C) group. After we exposed the hepatic hilum,
      ischemia was induced by clamping the hepatic artery and portal vein for 30
      minutes and then the liver was reperfused for 2 hours in the I/R group; a show
      procedure was done in the C group. Blood samples were obtained after exposure of
      the hepatic hilum (T1) and 2 hours after reperfusion in the I/R group (T2) and
      2.5 hours after T1 in the C group (T2). We measured glucose and insulin plasma
      concentrations. We determined the expressions of insulin signaling proteins,
      including insulin receptor (IR) beta unit (IR beta), IR substrate 1 (IRS-1), IRS
      2, and P85 in phosphatidylinositol 3-kinase (PI3K) and tyrosine phosphorylation
      of these proteins in liver and skeletal muscle. RESULTS: Plasma glucose
      concentrations increased in both groups at T2 (P < .01) and were higher in the
      I/R group (P < .01). Insulin concentrations in the I/R group did not change
      significantly at T2. Insulin concentrations at T2 were higher than those at T1 in
      the C group (P < .05). Expressions of insulin signal proteins showed no
      significant difference between the 2 groups; however, tyrosine phosphorylation of
      IR beta, IRS-1, IRS-2, and the interactions between IRS-1 in skeletal muscle or
      IRS-2 in liver and PI3K were significantly lower in the I/R group than the C
      group. CONCLUSION: Hepatic I/R inhibited insulin secretion and induced insulin
      resistance via down-regulation during the early steps in insulin signaling in
      rats.

PMID- 19100382
TI  - Vitamin E succinate reduces ischemia/reperfusion injury in steatotic livers.
AB  - Steatotic livers represent a growing proportion of marginal organs available for
      transplantation. These livers are highly prone to primary nonfunction following
      transplantation and are therefore routinely turned down for surgery. Given the
      elevated levels and sensitivity for reactive oxygen species (ROS) in these
      livers, we evaluated whether pretreatment with a targeted ROS scavenger, vitamin
      E succinate, increased survival and decreased injury after ischemia/reperfusion
      (I/R). For this study, ob/ob mice received 50 IU/d vitamin E succinate in
      supplemented vs control chow for 7 days, and were subjected to 15 minutes of
      total hepatic ischemia and 24 hours of reperfusion. Treatment resulted in a 5
      fold decrease in serum alanine aminotransferase (ALT) levels after reperfusion,
      mirrored by significant decreases in hepatocellular necrosis. These results
      suggested that targeted antioxidants such as vitamin E succinate may prove to be
      highly applicable for the pretreatment of steatotic donor livers, increasing
      their tolerance for I/R and the transplantation process.

PMID- 19100384
TI  - Potential for pulmonary protection by nebulized milrinone during warm ischemia.
AB  - OBJECTIVE: A method to compensate for the donor shortage may be the utilization
      of donation after cardiac death. The control of lung injury against warm ischemia
      is crucial in manipulating donors after cardiac death. Nebulization is a simple
      and feasible drug delivery route after cardiac death. Herein we have examined the
      potential effect of nebulized milrinone, a phosphodiesterase III inhibitor, on
      pulmonary warm ischemia. MATERIALS AND METHODS: Deeply anesthetized rats were
      euthanized by exsanguination. Lungs were exposed to warm ischemia with
      ventilation up to 2 hours. Milrinone was nebulized for 10 minutes at the
      beginning of warm ischemia (n = 5). In the control group (n = 5), normal saline
      was nebulized for the same time. At given intervals, the lungs were partially
      resected to measure adenine nucleotide and cyclic adenosine monophosphate levels.
      RESULTS: In both groups, lung tissue cyclic adenosine monophosphate levels
      decreased significantly at 2 hours after warm ischemia; however, there was no
      significant difference between the groups. Lung tissue adenosine triphosphate
      levels significantly decreased at 2 hours after ischemia in the control group,
      while they did not drop up to 2 hours in the milrinone group. Further, lung
      tissue adenosine triphosphate levels at 2 hours after ischemia were higher in the
      milrinone group than the control group. CONCLUSIONS: Our results confirmed that
      milrinone nebulization during warm ischemia maintained lung tissue adenosine
      triphosphate levels. Therefore, milrinone nebulization may have potential for
      lung protection against warm ischemia.

PMID- 19100385
TI  - Intestinal ischemia/reperfusion injury triggers activation of innate toll-like
      receptor 4 and adaptive chemokine programs.
AB  - BACKGROUND: Ischemia/reperfusion injury (IRI) is a major problem in intestinal
      transplantation. Toll-like receptor 4 (TLR4) has been implicated as a possible
      link between the innate and adaptive immune systems, however little data exists
      regarding TLR4 in intestinal IRI. The goal of this study is to evaluate the
      involvement of TLR4 in intestinal IRI and to assess the effect on T cell related
      chemokine programs. METHODS: C57BL6 mice underwent 100 minutes of warm intestinal
      ischemia by SMA clamping. Control WT mice underwent laparotomy without vascular
      occlusion. Separate survival and analysis groups were performed, and intestinal
      tissue was harvested at 1 hour, 2 hours, 4 hours, and 24 hours post-reperfusion.
      Analysis included histology, CD3 immunostaining, myeloperoxidase activity,
      Western blot, and PCR. RESULTS: Survival was significantly worse in the IRI group
      vs control (50% vs. 100%). IRI caused severe histopathological injury including
      mucosal erosions and villous congestion and hemorrhage. Myeloperoxidase activity
      increased in a time-dependent manner after IRI (2.71 0.25 at 1 hour, 2.92 0.25 at
      2 hours, 4 0.16 at 4 hours, 5.1 0.25 at 24 hours vs 0.47 0.11 controls, P < .05).
      Protein expression of TLR4 followed by NF-kappaB was increased after IRI.
      Additionally, mRNA production of IP-10, MIP-2, MCP-1, and RANTES was increased at
      all time-points, as was mRNA for ICAM-1 and E-selectin. CONCLUSION: This study is
      the first to demonstrate increased expression of TLR4 and NF-kappaB after warm
      intestinal IRI. This detrimental cascade may be initiated by TLR4 via NF-kappaB
      signaling pathways, implicating TLR4 as a potential therapeutic target for the
      prevention of intestinal IRI.

PMID- 19100386
TI  - Role of nitric oxide in ischemia-reperfusion injury and acute rejection in rat
      intestinal transplantation.
AB  - OBJECTIVE: This study was designed to evaluate the role of nitric oxide (NO) in
      ischemia-reperfusion injury (IRI) and acute rejection (AR) in rat intestinal
      transplantation, using administration of the NO inhibitor N(G)-nitro-L-arginine
      methyl ester (L-NAME). MATERIALS AND METHODS: Rats that underwent orthotopic
      allogeneic intestinal transplantation were assigned to 2 groups. In the normal
      allograft group (Wistar to Sprague-Dawley rats), L-NAME 0 mg/kg/d (group 1-1), 4
      mg/kg/d (group 1-2), 8 mg/kg/d (group 1-3), or 12 mg/kg/d (group 1-4) was
      injected intraperitoneally. In the high responder allograft group (Dark Agouti to
      Lewis rats), L-NAME 0 mg/kg/d (group 2-1) or 8 mg/kg/d (group 2-2) was injected
      intraperitoneally. Survival times were observed and maltose absorption tests
      performed as well as light microscopic examination of the grafts. RESULTS: The
      mean survival time of group 1-3 was significantly prolonged compared with group 1
      1 (P < .01). In group 2, the survival time of group 2-2 was significantly
      prolonged compared with group 2-1 (P < .01). Histological changes showed IRI was
      attenuated in group 1-2 compared with group 1-1, whereas it was aggravated in
      groups 1-3 and 1-4. Treatment with L-NAME (8 mg/kg/d) attenuated the graft damage
      of AR in groups 1 and 2. Maltose absorption tests showed that inhibition of NO
      impaired maltose absorption. CONCLUSION: This study suggested that NO plays a
      dual role as both a cytotoxic and a cytoprotective factor in IRI, and may serve
      as a kind of cytotoxic medium in AR in rat intestinal allotransplantation.

PMID- 19100387
TI  - Influence of single-nucleotide polymorphisms on C-reactive protein levels in
      chronic kidney disease before and after kidney transplantation.
AB  - INTRODUCTION: We sought to evaluate 2 single-nucleotide polymorphisms (SNPs) in
      the C-reactive protein (CRP) gene promoter region for their effects on CRP levels
      in chronic kidney disease (CKD) patients before and after a successful kidney
      transplantation. METHODS: Fifty CKD patients were evaluated before and at the
      first and second years after the graft. Two SNPs were studied, a bi-allelic (G-
      >A) at the -409 and a tri-allelic (C-->T-->A) variation at the -390 position in
      the CRP gene. RESULTS: All patients presented the -409GG genotype. At the -390
      position, the "A" allele was not found; there were 15 "CC" patients, 11 "TT"
      patients, and 24 "CT" patients. CRP levels were different among patients with
      various genotypes (P < .019). Also the presence of the allele "T" was sufficient
      to determine differences in CRP levels both in pretransplantation (P = .045) and
      at 1 year posttransplantation (P = .011), but not at the second year (P = .448).
      CONCLUSION: SNPs at the -390 position of the CRP gene promoter region influence
      CRP basal levels in such a way that the "C" allele correlated with the lowest and
      the "T" with the highest. We did not observe this influence in our patients at
      the second year posttransplantation.

PMID- 19100388
TI  - Tumours in end-stage kidney.
AB  - OBJECTIVE: Patients with end-stage kidney disease (ESKD) show a greater risk for
      renal cell carcinoma (RCC), which tends to be multifocal and bilateral. The
      malignant potential is unclear. The question is whether to remove both kidneys in
      patients with a tumor on one side only diagnosed by computed tomography (CT).
      MATERIALS AND METHODS: Kidney tumors were found in 14 patients with ESKD from
      January 2002 to December 2006. One was unfit for surgery. Thirteen patients
      underwent nephrectomy and 6 a bilateral procedure of whom only 2 had bilateral
      tumors on CT, 3 multiple tumors on the contralateral side, and 1 uncontrollable
      hypertension with tumors as an incidental finding. Tumors were found in all 19
      specimens. RESULTS: In 13 kidneys (68.4%), the tumors were multiple; in 6
      (31.6%), solitary. The types of tumor were: 13 (68.4%) papillary RCCs (PRCC), 9
      (47.4%) clear RCCs (CRCC), a combination of PRCC and CRCC in 4 (21.0%), and
      myxoid liposarcoma (with solitary PRCC contralaterally). The mean follow-up was
      short (19 +/- 15 months; maximum, 54 months). Only 1 patient died due to a tumor
      at 16 months after operation. CONCLUSIONS: There is a high risk for bilateral
      involvement. Patients who undergo unilateral nephrectomy must be regularly
      followed and contralateral nephrectomy carefully considered, mainly in
      transplanted patients on immunosuppression. Further studies are needed to give a
      definitive answer about the indications for surgery and the indications for
      contralateral nephrectomy as well. To date, prophylactic contralateral
      nephrectomy should not be a therapeutic standard.

PMID- 19100389
TI  - The source matters: no impact of the CCL2/MCP-1-1-2518G polymorphism of the donor
      on renal allograft outcome during the first year after transplantation.
AB  - Chemokines are involved in the recruitment of inflammatory cells to vascularized
      allografts. The chemokine CCL2/MCP-1 is expressed during allograft dysfunction,
      which is associated with the recruitment of inflammatory cells. Both intrinsic
      renal cells (donor origin) as well as infiltrating inflammatory cells (recipient
      origin) can be a source of CCL2/MCP-1. We previously demonstrated that the
      recipient MCP-1-2518G polymorphism is associated with increased CCL2/MCP-1
      production by inflammatory cells and decreased renal allograft survival. We
      evaluated the impact of the MCP-1-2518G polymorphism in donor cells on renal
      allograft outcomes. We enrolled 252 recipients of kidney allografts in this
      retrospective study who had received grafts from 152 cadaveric donors. The
      CCL2/MCP-1 genotype was assessed using genomic DNA isolated from cryopreserved
      donor splenocytes. Outcome parameters studied were acute biopsy proven rejection
      (Banff criteria), serum creatinine, and glomerular filtration rate (GFR) at 1
      year after transplantation, allograft loss, and death. MCP-1-2518 genotypes were
      in HW equilibrium. A/A was present in 125 (49.6%), A/G in 107 (42.5%), and G/G in
      20 (7.9%) donor kidneys. There were no significant differences in the number of
      rejection episodes, the number of allograft losses, serum creatinine, GFR, or
      overall survival 1 year after transplantation. In contrast with the detrimental
      effect of the CCL2/MCP-1 polymorphism of the recipient, the CCL2/MCP-1
      polymorphism of the donor has no impact on the allograft outcome during the first
      year after transplantation. The impact on the long-term outcomes needs further
      evaluation.

PMID- 19100390
TI  - Hand-assisted laparoscopic donor nephrectomy: a comparative study with
      conventional open donor nephrectomy in a single Chinese center.
AB  - BACKGROUND: Traditional open donor nephrectomy (ODN) is associated with good
      outcomes and excellent allograft function; nevertheless, it causes too much
      injury to the donor. Hand-assisted laparoscopic donor nephrectomy (HLDN) may
      accomplish these goals with less damage. We compared the outcomes of the hand
      assisted with the traditional open approach. We also investigated whether the
      availability of the HLDN approach affected a donor's decision and why he or she
      selected HLDN versus ODN. MATERIALS AND METHODS: We retrospectively analyzed
      donor and allograft outcomes for the first 65 patients undergoing HLDN at our
      institution compared with those of 32 patients undergoing traditional ODN.
      Patient data were obtained from medical record reviews and telephone interviews.
      RESULTS: HLDN and ODN were successfully completed in 97 (100%) donors. No
      conversion to open operation occurred among the HLDN group. The mean (standard
      deviation) operative durations were 157.92 (23.79) minutes for HLDN and 103.21
      (19.63) minutes for ODN (P = .000), and hospital stays were 5.00 (1.54) days for
      the HLDN group and 6.59 (0.79) days for the ODN group (P = .000). There was no
      significant difference between the 2 groups in postoperative donor (P = .541) and
      recipient (P = .337) renal functions. The primary reason encouraging donors was
      family obligations and bonds (70.1%); the availability of HLDN did encourage the
      decision (29.9%). Although all renal donors were aware of the option of HLDN, 28
      selected ODN because of financial reasons, another 4 patients due to safety
      concerns. The main reasons for choosing HLDN instead of ODN were less
      postoperative pain (60%) and cosmetic concerns (29.2%). CONCLUSIONS: HLDN was
      safe and feasible to procure a normally functional organ for live donor
      transplantation. The availability of the HLDN approach did affect a donor's
      decision. The main reason for choosing HLDN instead of ODN was less postoperative
      pain.

PMID- 19100391
TI  - Preoperative evaluation of donor kidney with 16-section computed tomography
      angiography: a pilot study.

PMID- 19100392
TI  - The role of fcgamma receptor gene polymorphism in pediatric renal transplant
      rejections.
AB  - The aim of the study reported herein was to determine whether panel-reactive
      antibody (PRA) and FcgammaR gene polymorphism act in the same way on acute
      rejection (AR) and chronic rejection (CR) in children who have undergone renal
      transplantation. The study evaluated 56 children who underwent transplantation
      and 115 healthy subjects. AR was observed in 13 cases; CR was observed in 7
      patients. The assessment for FcgammaR of the groups in which AR was present
      showed statistical significance only for the FcgammaIIA genotype. There was no
      statistical significance for either the FcgammaIIIA or FcgammaIIIB genotypes.
      Assessment of the FcgammaIIA, IIIA, and IIIB genotypes of the groups in whom CR
      was present did not show statistical significance. As a result, the prediction of
      graft survival among transplant recipients is possible using molecular biology.
      The results of our study showed that individuals of the FcgammaRIIA genotype
      seemed to have a poorer prognosis similar to some autoimmune diseases. These
      individuals constitute a risk group for AR. If other studies are conducted with
      more patients to demonstrate the relationship of other FcgammaRs to rejection,
      the resultant predictive knowledge about the value of genotypes may lead to
      improved outcomes following renal transplantation.

PMID- 19100393
TI  - High serum level of the soluble CD30 identifies Chinese kidney transplant
      recipients at high risk of unfavorable outcome.
AB  - BACKGROUND: We sought to investigate the relationship between serum level of
      sCD30 and recipient/graft survival rates, rejection types, as well as other
      prognostic factors among Chinese kidney transplant patients. MATERIALS AND
      METHODS: We performed enzyme-linked immunosorbent assays of serum sCD30 levels in
      duplicate among retrospective cohort of 707 renal transplant patients. RESULTS:
      The incidences of rejection increased in relation to the pretransplant sCD30
      level. The reversal rates of rejection were 100%, 90.6%, and 78.6% for the low,
      intermediate, and high sCD30 groups. This observation suggested that high levels
      of sCD30 and pretransplant panel-reactive antibody (PRA)-positive patients are
      risk factors for acute rejection with odds ratios of 6.862 and 1.756. High sCD30
      was an independent risk factor for functional graft survival. The 5-year graft
      survival rates were 99.39% +/- 6.1%, 93.11% +/- 1.93%, and 82.07% +/- 3.97% among
      the low, intermediate, and high sCD30 groups, while the 5-year recipient survival
      rates were 89.25% +/- 2.41%, 91.82% +/- 1.64%, and 88.85% +/- 2.36%,
      respectively. Increased sCD30 levels were observed among patients who were PRA
      positive, cytomegalovirus antigens or antibodies positive, on long-term dialysis,
      and <or= 20 years old. CONCLUSIONS: Pretransplant sCD30 serum levels reflect
      immune status.

PMID- 19100394
TI  - Level of soluble CD30 after kidney transplantation correlates with acute
      rejection episodes.
AB  - Measurement of soluble CD30 (sCD30) levels may predict acute rejection episodes
      (ARE). To explore the value of sCD30 after transplantation, we tested serum sCD30
      levels in 58 kidney transplant cases at 1 day before and 7 and 28 days after
      transplantation by enzyme-linked immunosorbent assay (ELISA). The incidences of
      ARE after kidney transplantation were recorded simultaneously. Meanwhile, 31
      healthy individuals were selected as a control group. The results showed a
      relationship between sCD30 level in serum before kidney transplantation and the
      incidence of ARE. However, the relationship was more significant between serum
      sCD30 levels at day 7 after kidney transplantation and the incidence of ARE.
      There was no obvious relationship between serum sCD30 levels at day 28 after
      kidney transplantation and the incidence of ARE. These results suggested that the
      level of sCD30 at day 7 posttransplantation provides valuable data to predict
      ARE.

PMID- 19100395
TI  - Lymphocytic HLA-A mRNA is a reliable indicator of acute rejection in renal
      transplantation.
AB  - BACKGROUND: Rejection in renal transplantation is the most frequent event causing
      transplant failure. It is important to identify parameters to predict rejection,
      which are helpful in a timely fashion. METHODS: Fifty-nine renal transplant
      recipients were divided into two groups: group 1 (stable renal function) and
      group 2 (acute rejection episodes). The levels of HLA-A mRNA in peripheral blood
      lymphocytes (both pre- and posttransplantation) were measured by reverse
      transcriptase-polymerase chain reaction (RT-PCR) with glucose-6-phosphate
      dehydrogenase (G6PDH) as an internal reference. The TEST software was used to
      analyze the relative expressions of HLA-A mRNA. RESULTS: There was no statistical
      significance between features of the two groups pretransplant versus normal
      controls. Posttransplant, the HLA-A mRNA levels decreased significantly compared
      to those of pretransplant and normal control individuals. The levels of HLA-A
      mRNA among the 10 patients with acute rejection episodes were significantly
      increased. There was no significant change in the lymphocyte populations in the
      early stage of an acute rejection episode compared with the prerejection value.
      CONCLUSION: HLA-A mRNA expression was strongly correlated with immune status. The
      HLA-A mRNA levels may provide an effective and reliable indicator to predict
      acute rejection episodes in renal transplantation.

PMID- 19100396
TI  - Role of TH1/TH2 cytokines in kidney allograft rejection.
AB  - One of the major issues in contemporary kidney transplantation is prevention of
      acute allograft rejection episodes (AREs). Cytokines are crucial mediators of
      immune reactions leading to AREs. We correlated serum Th1/Th2 cytokine
      concentrations with AREs. The project included 44 patients undergoing kidney
      transplantation. During the 3-month period following the transplantation, ARE was
      diagnosed in 11 patients. Serum samples collected 1 day before and 2, 7, 14, and
      30 days after transplantation were tested for interleukin (IL)-2, IL-4, IL-5, IL
      10, interferon (IFN)-gamma, tumor necrosis factor (TNF)-alpha concentrations
      using flow cytometry. Nonrejection (NONAR) and rejection (ARE) groups of patients
      did not show significant differences in baseline demographic characteristics. We
      observed that higher pretransplantation serum levels of IFN-gamma (P = .000003)
      and IL-10 (P = .000001) were associated with AREs. Our analysis also showed
      slightly higher IL-4 serum levels among NONAR patients up to 7 days
      posttransplantation, followed by a drop in concentrations in NONAR patients. In
      contrast, there was a continuous increase among ARE patients. No significant
      differences were observed in plasma levels of IL-2, IL-5, IL-10, or TNF-alpha
      between the two groups. Higher pretransplantation levels of IFN-gamma and IL-10
      observed in ARE patients indicated ongoing nondetected, probably nonspecific,
      inflammatory processes able to intensify an immune response directed against the
      transplanted organ leading to its acute rejection. Higher levels of IL-4 prior to
      and shortly after transplantation may have protective effects on graft survival.
      However, a prolonged, increased production of IL-4 after transplantation can also
      contribute to AREs.

PMID- 19100397
TI  - High-dose intravenous immunoglobulin and rituximab treatment for antibody
      mediated rejection after kidney transplantation: a cost analysis.
AB  - Antibody-mediated rejection (AMR) generally occurs in highly sensitized patients.
      A pilot study was performed on 7 consecutive patients with AMR to assess the
      efficacy of high-dose intravenous immunoglobulin (IVIG; 2 g/kg) + rituximab (RTX;
      375 mg/m(2)) without plasmapheresis. After a 24-month follow-up, 1- and 2-year
      allograft survivals were 86% and 58%, respectively. C4d became negative in 1
      patient posttreatment. Donor-specific antibody (DSA) titers decreased to less
      than 1:4 in 2 cases. There were 4 infectious complications and 1 case of aseptic
      meningitis followed by cranial nerve VI palsy. The average hospital charge for 1
      administration of IVIG + RTX, including hospital stay and renal biopsy expenses,
      was approximately $49,000. A combination of IVIG + RTX in late AMR may be
      beneficial but is an expensive treatment approach for selected renal transplant
      patients.

PMID- 19100398
TI  - Multifocal renal allograft biopsy: impact on therapeutic decisions.
AB  - OBJECTIVE: There are no data to support the suggestion that samples removed from
      one segment of the transplanted kidney are representative of the whole graft. The
      aim of this study was to compare the histological differences between biopsies
      obtained from different portions of the renal allograft and their impact on
      treatment recommendations. PATIENTS AND METHODS: Two hundred percutaneous
      biopsies were performed on kidney allografts and samples were collected from the
      upper and lower poles (100 kidneys). All samples were randomized and blindly
      reviewed. We obtained the discordance rates between the poles for the grading of
      acute rejection and for the diagnosis of nephrotoxicity due to immunosuppression.
      We also checked if the differences found were sufficient to call for different
      clinical recommendations. These values were compared with the intrapathologist
      variation rates. RESULTS: In 70 kidneys adequate sampling was obtained from both
      poles. The diagnosis of acute rejection were made in 17. The discordance rate
      between the upper and lower poles was 82.3% (kappa = 0.34), higher than the
      intrapathologist variation (P = .002). Nephrotoxicity was found in 14 kidneys.
      The discordance rate between the upper and lower poles was 28.6% (kappa = 0.88),
      with no difference compared with the intrapathologist variation. In 14 of the 70
      kidneys (25.7%), discordances between poles had impact on clinical
      recommendations, most of these cases due to different gradings of acute rejection
      (78%). This number was higher than the intrapathologist variation (P = .04).
      CONCLUSIONS: The histopathological changes in the kidney allograft are not always
      homogeneous. This heterogeneity may affect the therapeutic recommendations.

PMID- 19100399
TI  - Long-term efficacy of induction therapy with anti-interleukin-2 receptor
      antibodies or thymoglobulin compared with no induction therapy in renal
      transplantation.
AB  - BACKGROUND: Although the utility of antibody induction therapy has been
      demonstrated in clinical trials, the ideal regimen to use based on patient risk
      factors has not been fully elucidated. The objectives of this study were to
      determine the impact of either anti-interleukin-2 receptor antibodies (IL-2RA) or
      thymoglobulin induction therapies versus no induction therapy on acute rejection
      rates and on 3-year graft survival rates. METHODS: This retrospective analysis
      compared 3 patient groups-those who did not receive induction, those who received
      IL-2RA induction, and those who received thymoglobulin induction. RESULTS: Three
      hundred eleven patients were included in this study. Patients were well matched
      for demographic and immunologic characteristics in the noninduced and IL-2RA
      induction therapy groups; the thymoglobulin induction group included
      significantly higher risk patients. The acute rejection rates were significantly
      lower in the IL-2RA and thymoglobulin groups when compared with the no induction
      therapy group (28% vs 15% vs 41%, respectively; P = .001), which was confirmed
      with multivariate analysis. The 3-year graft loss rates (no induction 21% vs IL2
      RA induction 19% vs thymoglobulin induction 25%; P > .50) and creatinine
      concentrations (no induction 1.8 +/- 0.7, IL-2RA induction 2.0 +/- 1.0, and
      thymoglobulin induction 1.9 +/- 1.2; P = .47) were similar between all groups.
      CONCLUSION: The use of induction therapy significantly reduces the incidence of
      acute rejection. The use of thymoglobulin induction equalizes 3-year graft
      survival rates in high-risk patients to those seen in low-risk patients receiving
      either no induction or IL-2RA induction.

PMID- 19100400
TI  - Effect of degree of obesity on renal transplant outcome.
AB  - Obesity in renal transplantation has proven to affect both patient and graft
      survival. The scientific community seems to be split into 2 groups: one claims
      similar outcomes among obese and nonobese, showing only marginally increased
      postoperative complications; whereas the other group report a higher rate of
      complications, including graft loss and mortality. These results did not provide
      sufficient evidence to be applied in practice. In this study we analyzed the
      outcomes of obese recipients of renal transplant in our institution. One hundred
      fourteen renal transplantations were performed between January 1993 and December
      2003. To estimate the impact of various degrees of obesity, the patients were
      allocated into 2 cohorts: Group A (body mass index [BMI] 30-34.9) and Group B
      (BMI 35 and greater). We analyzed patient and donor characteristics. Wound
      infection rates were similar in the 2 groups. The aggregate Group A and B patient
      survival rate was 95.6% at 1 year and 93% at 5 years. Graft survival rate was
      93.9% at 1 year and 88% at 5 years. However, the analysis of the outcomes in the
      2 groups with different degrees of obesity showed that the patient survival rate
      at 1 year in Group A was 98.9% (1 death) and 95.6% at 5 years (4 deaths). In
      Group B the patient survival rate at 1 year was 87.5% (3 deaths; P = .007) and at
      5 years was 79.2% (P = .006). Graft survival rate in Group A was 98.9% (1 graft
      loss) at 1 year and 94.5% (5 graft losses) at 5 years; in Group B the graft
      survival rate was 75% (6 graft loss) at 1 year and 63% (9 graft losses) at 5
      years (P < .0001 both at 1 and 5 years). The present study showed that overall
      obese recipient outcomes were as expected when evaluating the obese as a single
      group of recipients with a BMI >30. The overall patient and graft survival did
      not show particularly different results from already published studies claiming
      similar outcomes. However, this series showed different outcomes when we divided
      them into 2 groups by BMI. There was a remarkable difference between moderate
      obese (Group A) and morbid obese (Group B) recipients as regards patient and
      graft survival. It is possible that the excellent outcome in Group A may be the
      result of super-selection and stringent cardiovascular risk screening that is
      implemented for this category of potential recipients. Obese recipients with a
      BMI of >35 are a high-risk category. Because of the difference in the outcomes of
      the 2 groups, it does not seem reasonable to address obese recipients as a single
      group. We believe that obese patients should not be discriminated simply on the
      basis of the BMI. A strict evaluation should be performed before denying the
      opportunity to receive a renal transplant to these patients.

PMID- 19100401
TI  - Deceased donor kidney transplantation in elderly patients: is there a difference
      in outcomes?
AB  - INTRODUCTION: There is a paucity of data on long-term outcomes of older kidney
      recipients. Our aim was to compare the early and long-term outcomes of deceased
      donor kidney transplantation in patients aged >or=60 years with outcomes in
      younger recipients. MATERIALS AND METHODS: From 1998 to 2005, we performed 271
      deceased donor kidney transplants. There were 76 recipients (28.1%) >60 years
      old. Older candidates were carefully selected based on their physiologic,
      cardiac, and performance status. Demographic data, including clinical
      characteristics, early complications, mortality, and patient and graft survival
      rates, were collected and analyzed. RESULTS: Older patients had comparable
      perioperative mortality and morbidity, incidence of delayed graft function (DGF),
      length of stay, and readmissions compared with younger patients. The rates of
      acute rejection and major infections were also comparable between the 2 study
      groups. Among older recipients, 25/76 (32.1%) patients received extended criteria
      donor kidneys compared with only 35/195 (17.9%) of younger patients (P < .001).
      Nevertheless, equivalent 1-, 3-, and 5-year allograft survival rates were
      observed in elderly and young patients; 91.5% versus, 92.5%, 78.5% versus 81.9%,
      and 75.6% versus 78.5%, respectively. Overall patient survival was also
      comparable in both groups. CONCLUSION: Kidney transplantation in appropriately
      selected elderly recipients provides equivalent outcomes compared with those
      observed in younger patients. These observations support the notion that older
      recipients should not lose access to deceased donor kidney transplantation in the
      effort to achieve a perceived gain in social utility.

PMID- 19100402
TI  - Outcome after renal transplantation in a "senior" program: the Croatian
      experience.
AB  - BACKGROUND: The Eurotransplant "senior" program allocates kidneys from elderly
      donors to patients >65 years old. It aims to increase the number of renal
      transplantations. Kidneys are allocated locally without human leukocyte antigen
      (HLA) matching to decrease the cold ischemia time. Croatia has introduced its own
      "senior" program based on HLA matching. We compared results with those from
      Eurotransplant. METHODS: We identified and prospectively followed all patients
      aged of >or=65 years who underwent a first renal transplantation. We recorded
      their HLA matching, cold ischemia time, renal function, surgical and medical
      complications, and duration of hospitalization. RESULTS: Through October 2007, 22
      elderly patients received an allograft from donors who were >65 years old. There
      were 8 female and 14 male patients of mean age at transplantation of 67.4 years.
      Mean donor age was 66 years. The number of HLA mismatches ranged from 1 to 5, and
      cold ischemia time from 7 to 15 hours. One-year patient survival was 95.4%, and
      graft survival was 81.8%. Delayed graft function, defined as the need for
      dialysis for >7 days after transplantation, occurred in 63.6% of patients. Older
      recipients required prolonged hospitalization after transplantation (45 days;
      range, 16-131). Frequent posttransplant complications included posttransplant
      diabetes mellitus in 1 patient, delayed wound healing in 5 patients, and
      lymphocoel in 2 patients. Maligancies occurred in 3 patients, neoplasm of the
      native kidney, posttransplant lymphoproliferative disease, and skin cancer. One
      patient experienced acute rejection that was successfully treated with steroids.
      Seventeen patients experienced 20 viral infections. There was only 1 serious
      infection (pulmonary tuberculosis). The major problems were cardiovascular
      complications which occurred in 40.9% of patients.

PMID- 19100403
TI  - T-cell function in maintenance renal transplant patients receiving mycophenolate
      mofetil and steroids with or without tacrolimus.
AB  - Nephrotoxicity-sparing protocols, using mycophenolate mofetil (MMF) and steroids
      without calcineurin inhibitors (CNIs) or mammalian target rapamycin (mTOR), could
      be used to treat maintenance renal transplant patients. However, the risk for
      acute rejection seems to be high. The aim of this pharmacodynamic study was to
      analyze T-cell function, T-cell activation, and T-cell proliferation among
      patients receiving MMF and steroids (n = 15) compared with patients receiving
      immunosuppression with CNI-based therapy including tacrolimus, MMF, and steroids.
      Our data suggested that among stable maintenance patients, dual therapy with MMF
      and steroids might provide a similar reduction in T-cell proliferation and T-cell
      activation as that observed among patients on standard immunosuppressive therapy.
      As expected, intralymphocytic interleukin-2 (IL-2) and tumor necrosis factor
      alpha (TNF-alpha) expressions were higher in patients not receiving CNIs.

PMID- 19100404
TI  - Renal graft outcome in simultaneous kidney transplantation combined with other
      organs: experience of a single center.
AB  - AIM: We report the renal graft outcomes among a series of patients who underwent
      simultaneous combined liver-kidney transplantations (CLKT) or heart-kidney
      transplantations (CHKT) at a single center. METHODS: From 1975 to December 31,
      2007, we performed 1524 kidney transplantations, 427 liver transplantations, and
      483 heart transplantations, including 7 simultaneous CLKT and 2 CHKT. We analysed
      the main patient characteristics, renal graft outcomes, and patient survivals.
      RESULTS: CLKT indications were as follows: alcoholic cirrhosis (n = 5) and
      hepatitis C virus (n = 2) with chronic glomerulonephritis (n = 5), hypertensive
      nephropathy (n = 1), and polycystic disease (n = 1). Cold renal ischemia time was
      6.9 hours (range, 6-9). In 5 patients there were no kidney rejection episodes; 3
      of these patients are alive with creatinine levels between 1.4 and 1.7 mg/dL with
      an average follow-up of 6.9 years (range, 10 months-8 years). One patient died of
      esophageal cancer at 13 years after transplantation with a serum creatinine level
      of 1.16 mg/dL and another died of breast cancer at 7 years after transplantation
      with a creatinine level of 1.1 mg/dL. One patient lost his renal graft just after
      the kidney transplantation due to renal vein thrombosis. The last patient
      suffered 1 episode of acute rejection and lost his kidney 5 years later due to
      chronic rejection. CHKT indications were as follow: dilated myocardiopathy (n =
      2) and chronic glomerulonephritis (n = 1) or interstitial nephropathy (n = 1).
      The cold renal ischemia time was 4 hours. There were no acute rejection episodes.
      One patient is alive with a creatinine level of 2.05 mg/dL at 6 years after the
      transplantation; the other patient lost his kidney due to chronic rejection at
      270 days after simultaneous CHKT, and 2 years later received a second kidney that
      is functioning normally. CONCLUSIONS: Simultaneous CLKT and CHKT in selected
      cases provided satisfactory long-term outcomes in both graft function and patient
      survival with lesser number of acute rejection episodes than nonsimultaneous
      transplantations. They are worthy options for patients with liver or heart
      failure associated with renal failure.

PMID- 19100405
TI  - Living related kidney transplantation in Libya: a single center experience.
AB  - OBJECTIVE: The aim of this study was to establish a successful living related
      kidney transplantation program in Libya and to bring down health care costs in
      management of patients with end-stage renal disease. PATIENTS AND METHODS: Since
      the transplantation program was launched on August 17, 2004, 135 patients have
      been transplanted up to August 17, 2007. The donors and recipients were screened
      prior to transplantation. Our immunosuppressive protocol was cyclosporine-based.
      Both donors and recipients were followed in the transplant outpatient clinic.
      RESULTS: Among 135 accepted pairs, 133 cases (98.5%) were genetically related
      donors and recipients and 2 cases were emotionally related. Mean donor age was 37
      +/- 9.5 years (range, 18-56 years). Recipient age was significantly lower,
      namely, 37 +/- 13.6 years (range, 7-67 years). Among the recipients, 95 (70.4%)
      were males and 40 (29.6%) females, while among the donors, 102 (75.6%) were males
      and 33 (24.4%) females. The most common donor-recipient relationship was brother
      to-brother. There was no early or late surgical mortality among donors. Delayed
      graft function was observed in 3 patients (2.2%), acute rejection in 6 (4.4%),
      and posttransplantation infections in 8 (5.9%). Urinary tract infections were
      diagnosed in 6 patients (4.4%) and pneumonia in 3 (2.2%). Postsurgical
      complications included ureteric kink in 2 patients (1.5%) and an anastomotic
      urine leak in 4 (3.0%). At 36 months, graft survival was observed in 130 patients
      (96.3%) and patient survival in 126 (93.3%). CONCLUSION: The Libyan National
      Organ Transplant Program has been successful with results comparable to
      international levels.

PMID- 19100406
TI  - Microchimerism in peripheral blood and urine in renal transplant recipients:
      preliminary results.
AB  - The role of microchimerism in peripheral blood and urine of renal transplant
      recipients remains a matter of debate, depending on the sensitivity of the
      methods used for detection. We studied 17 female renal transplant recipients who
      had received renal allografts from male donors. Polymerase chain reaction (PCR)
      was applied to blood and urine for the microsatellite markers D1S80, DYZ1, TH01,
      and kalphai SE33. Detection of DYZ1 that is present only on the Y chromosome was
      considered proof for microchimerism. No microchimerism was detected in peripheral
      blood, whereas it could be detected in the urine of 8/17 (48%) patients. There
      were no differences between patients with and without microchimerism regarding
      patient age, dialysis vintage, immunosuppression, time post-transplantation, and
      allograft function as measured using serum creatinine, creatinine clearance, and
      proteinuria. Two patients in each group showed chronic allograft dysfunction.
      These findings raise questions regarding the role of microchimerism in renal
      transplantation.

PMID- 19100407
TI  - Mast cells tryptase in patients after renal transplantation.
AB  - Mast cells (MC) are involved in the pathogenesis of interstitial fibrosis, acute
      renal transplant rejection, and chronic allograft nephropathy. The aim of this
      study was to evaluate MC tryptase concentrations in the sera of 58 renal
      transplant recipients at various times after surgery in relation to graft
      function. We observed that kidney transplantation patients showed much higher
      serum tryptase concentrations than healthy controls. We demonstrated a positive
      correlation between serum tryptase concentration and hemoglobin, hematocrit, red
      blood cell count, and hepatic cell damage. We were not able to show any direct
      correlation between serum tryptase concentration and graft function. The clinical
      relevance of these findings demand further investigation.

PMID- 19100408
TI  - Hospital costs of renal transplant management.
AB  - Renal transplantation is considered to be a cost-effective therapy, but hospital
      medical costs are not accurately known. The aim of this work was to evaluate the
      costs of hospital stay for renal transplantation. This retrospective study
      included all patients who underwent renal transplantation between January 1,
      2004, and December 31, 2005, in our University hospital. The incurred costs were
      determined using our center's analytical accounting (AA). The mean local cost was
      then compared with the median national cost of hospitalization for renal
      transplantation, based on a sample of participating centers contributing to the
      National Cost Scale (NCS) per homogenous diagnosis-related group (DRG). These
      mean costs were weighed against the financing obtained by national rates of the
      case-mix based payment system (termed T2A). Data were collected from 77 patients.
      Their mean length of stay was 19.4 days. AA determined the cost of management to
      be euro14,100 per patient. National economic approaches were significantly
      higher: euro16,389 for NCS and euro17,369 for national rates. Thus, the specific
      DRG rate (case mix index) of renal transplantation covers the expenses incurred
      by our center. These results are rather interesting; however, it is unlike those
      obtained for the management of other diseases such as acute myeloid leukemia,
      where T2A underestimates the actual cost by 2-4 times. Last, the hospital budget
      and T2A must be considered as a whole. The fact that DRGs with favorable and
      unfavorable pricing balance out should be taken into account.

PMID- 19100409
TI  - ABO blood type incompatible kidney transplantation without splenectomy prepared
      with plasma exchange and rituximab.
AB  - We have designed a protocol for ABO-incompatible kidney transplantations based on
      preoperative plasmapheresis with a tacrolimus/mycophenolate
      mofetil/methylprednisolone/basiliximab protocol using low-dose rituximab (200
      mg/body) instead of splenectomy to prevent antibody-mediated acute rejection.
      Eight patients successfully received transplants with this protocol. The titers
      of anti-A and -B antibodies as well as the number of CD20(+) cells were readily
      maintained at a low level posttransplantation. There were no side effects. All
      patients have renal transplant function with a follow-up of 1-34 months.

PMID- 19100410
TI  - Paradoxical depression in renal transplant recipients.
AB  - Paradoxical depression occurs despite a completely successful transplantation
      without tissue rejection or other medical complications. In this study, the
      occurrence of paradoxical depression was retrospectively investigated among 1,139
      Japanese successful renal transplant recipients January 1997 through September
      2006. Among the 1,139 recipients, 103 visited the Department of Psychiatry after
      renal transplantation, including 40 with depressive symptoms and 15 with a
      physical problem considered to have nonparadoxical depression. The other 25
      recipients were considered to have paradoxical depression; that is, more than
      half of the 40 recipients with depressive symptoms had paradoxical depression.
      There were no significant differences in the clinical characteristics, including
      average age at the time of renal transplantation, rate of living-donor
      transplantation, rate of ABO incompatibility, method of dialysis (hemodialysis or
      peritoneal dialysis), duration of dialysis, and time interval between the renal
      transplantation and the initial visit to the Department of Psychiatry among the 2
      groups. These results suggested that there was another risk factor or
      interactions between factors. Of the 25 recipients, 6 had relationship problems,
      6 had social-rehabilitation problems, and 13 had mentioned no clear psychological
      problems. These psychological factors might in fact be related to the loss of an
      imagined past. Additional consecutive prospective studies are needed-a
      challenging prospect for consultation liaison psychiatrists in the field of
      transplantation.

PMID- 19100411
TI  - Combined epidural and general anesthesia for paediatric renal transplantation-a
      single center experience.
AB  - BACKGROUND: Appropriate anesthesia for pediatric renal transplantation requires
      stable intraoperative hemodynamics, optimal perfusion of the newly transplanted
      kidney and good analgesia during recovery. The aim of this study was to assess
      the preliminary application, success and safety of combined epidural and general
      anesthesia in pediatric renal transplantation in a small cohort. METHODS: We
      retrospectively reviewed the anesthesia records of 46 consecutive pediatric
      patients who received renal transplantation under combined epidural and general
      anesthesia from January 2003-2007. RESULTS: The mean patient age and weight were
      13.2 +/- 2.4 years and 25.7 +/- 5.46 kg, respectively. The infused crystalloids,
      20% albumin and red blood cell concentrates were 120 +/- 2 mL/kg to achieve a CVP
      of 13 to 15 mm Hg. Brisk diuresis was observed in all patients. Epidural tramadol
      (2 mg/kg) provided good postoperative analgesia in 89% patients. 15% patients
      developed radiological evidence of pulmonary edema, only one required mechanical
      ventilation for hypoxemia. Minor adverse effects were nausea and vomiting (17.5%)
      and convulsions (8.5%). No perioperative mortality or major morbidity was
      recorded. CONCLUSION: Epidural anesthesia is a useful adjunct to general
      anesthesia due to stable intraoperative haemodynamics and good postoperative
      analgesia.

PMID- 19100412
TI  - Different effect of cyclosporine and tacrolimus on renal expression of P
      glycoprotein in human kidney transplantation.
AB  - OBJECTIVE: To investigate the differential effects of cyclosporine (CsA) and
      tacrolimus (TAC) on renal expression of P-glycoprotein (P-gp) in a cohort of
      kidney transplant recipients. METHODS: We enrolled 78 cadaveric kidney transplant
      recipients recurring basal immunosuppressive protocol with prednisone +
      mycophenolate mofetil + calcineurin inhibitor (CsA or TAC). RESULTS: We performed
      a 3-year analysis of 60 patients. There was no difference in age, gender, or cold
      ischemic time between two groups, Serum creatinine, urine protein, and blood fat
      levels of the CsA group were significantly higher than the TAC group (P < .05),
      while the creatinine clearance was remarkably lower than the TAC group (P < .05).
      The incidence of tubular atrophy, arteriohyalinosis, and interstitial fibrosis
      and nephrotoxic lesions among the CsA group were higher than the TAC group, as
      well as the chronic allograft nephropathy (CAN) Banff score (P < .05). P-gp was
      predominantly present in the a tubular apical membrane, basal membrane, and
      cytoplasm. The intensity and extent of tubular staining score in the CsA group
      were lower compared with the TAC group (P < .01 and P < .05, respectively).
      CONCLUSION: Less P-gp expression in the CsA group than the TAC group may be the
      molecular action pathway of the high incidence of CsA nephrotoxicity and CsA
      induced CAN. This study perhaps unraveled a novel interpretation that the
      differences of CsA and TAC on long-term allograft survival were due to increases
      dynamic effects of CsA at the exposures employed in this study.

PMID- 19100413
TI  - Loss of renal function is associated with deterioration of health-related quality
      of life in kidney transplant patients.
AB  - OBJECTIVE: The evaluation of health-related quality of life (HRQOL) is becoming
      an important measure of the outcomes of kidney transplantation. The aim of this
      study was to evaluate whether deterioration of renal function was associated with
      a worse HRQOL in kidney transplant patients (KTP) compared with patients
      experiencing chronic native kidney insufficiency. PATIENTS AND METHODS: HRQOL was
      assessed in 128 stable KTP and 102 chronic kidney disease patients (CKDP) using
      the SF-36 health survey. The 2 groups were matched for age, sex, sociodemographic
      conditions, and renal function, the only difference being that KTP had
      experienced hemodialysis treatments before transplantation. RESULTS: Overall, KTP
      revealed a satisfactory HRQOL compared with CKDP. At variance with CKDP, KTP with
      estimated creatinine clearances >60 mL/min versus <60 mL/min showed higher scores
      among 7 of 8 SF-36 categories: physical function (PF), role physical (RP), bodily
      pain (BP), general health (GH), vitality (VT), role emotional (RE), and mental
      health (MH). Estimated creatinine clearance showed a significant positive
      correlation with PF (P = .0004), RP (P = .008), BP (P = .01), GH (P = .0001), VT
      (P = .001), RE (P = .03), and MH (P = .02), but exclusively in KTP. Multiple
      regression analysis confirmed in KTP that the scale scores of PF, RP, GH, VT, and
      RE were significantly dependent on creatinine clearance. CONCLUSION: Our data
      demonstrated that among KTP deterioration of renal function was associated with a
      worse HRQOL.

PMID- 19100414
TI  - Apelin, a novel adipocytokine, in relation to endothelial function and
      inflammation in kidney allograft recipients.
AB  - Apelin, a newly discovered adipocytokine produced by white adipose tissue, is
      also expressed in kidney and heart. It has been reported that apelin is related
      to echocardiographic features in hemodialyzed patients. Cardiovascular disease is
      a major contributor to the mortality and morbidity among patients with chronic
      renal failure as well as kidney allograft recipients. The aim of this study was
      to assess the association between apelin and coronary artery disease (CAD) among
      kidney allograft recipients. We investigated plasma apelin levels in 100
      clinically stable, kidney allograft recipients with versus without CAD. We also
      assessed markers of endothelial cell injury-von Villebrand factor (vWF),
      thrombomodulin, intracellular adhesion molecule (ICAM), and CD146; markers of
      inflammation-high-sensitivity-reactive protein (hsCRP); other hemostatic
      parameters-tissue plasminogen activator (tPA) and its inhibitor (PAI-1); as well
      as other adipocytokines-adiponectin and resistin-using commercially available
      kits. Markers of endothelial dysfunction and inflammation were significantly
      elevated among patients with CAD levels, as well as with CAD or diabetes,
      compared with those without CAD. Apelin was significantly lower among patients
      with CAD, but higher in diabetic patients. Apelin content was similar in
      hypertensive versus normotensive kidney allograft recipients. We observed
      significant correlations between apelin and ICAM, resistin, adiponectin, calcium,
      phosphate, alanine and aspartate aminotransferase levels, with CAD or diabetes.
      Upon multiple regression analysis as well as CAD, adiponectin, and ICAM were
      predictors of apelin. Apelin was significantly reduced in kidney allograft
      recipients with CAD; its level was predicted by the presence of CAD, endothelial
      damage, or inflammation. Apelin and other adipocytokines may be associated with
      inflammation and its clinical consequences.

PMID- 19100415
TI  - Endothelial function and novel adhesion molecule CD44 in kidney allograft
      recipients.
AB  - BACKGROUND: Disturbances in hemostasis and endothelial damage are common
      complications of kidney disease. Endothelial dysfunction may link these 2
      processes and inflammation is closely related to endothelial dysfunction.
      PATIENTS AND METHODS: This cross-sectional study on serum concentrations of
      markers of endothelial damage and inflammation in relation to adhesion molecules
      was performed in 90 kidney allograft recipients and 30 healthy volunteers. We
      measured markers of endothelial damage-von Willebrand factor (vWF),
      thrombomodulin, intracellular adhesion molecule (ICAM), vascular adhesion
      molecule (VCAM), CD146, CD44, and CD40L; markers of inflammation-high-sensitivity
      C-reactive protein (hsCRP), tumor necrosis factor alpha (TNFalpha), and
      interleukin-6 (IL-6); and other hemostatic parameters-thrombin-antithrombin
      complexes (TAT), plasmin-antiplasmin complexes, and thrombin activatable
      fibrinolysis inhibitor (TAFI) using commercially available kits. RESULTS: Markers
      of endothelial dysfunction and inflammation were significantly elevated in kidney
      allograft recipients compared with control subjects. CD44 was independently
      related to hsCRP (r = .37; P < .01), ICAM (r = .23; P < .05), eGFR (r = -.37; P <
      .01), thrombomodulin (r = .43; P < .001), VCAM (r = -.44; P < .001), hemoglobin
      (r = -.26; P < .01), red blood cell count (r = -.25; P < .05), creatinine (r =
      .37; P < .01), CD146 (r = .34; P < .01), and CD40L (r = .23; P < .05). Upon
      multiple regression analysis the predictors of elevated CD44 were hsCRP
      concentration (beta = .25; P < .05), CD146 (beta = .39; P < .05), creatinine
      (beta = .55; P < .01), and thrombomodulin (beta = .39; P < .05) with an adjusted
      R(2) = .40 (F = 4.12; P < .00028; SE of estimate = 151.19). CONCLUSIONS: As
      demonstrated in multiple regression analysis, kidney function was strictly linked
      to the degree of inflammation and endothelial injury. Endothelial cell injury and
      the presence of an inflammatory state, as reflected by elevated marker
      concentrations, and endothelial activation/injury may play roles in the
      pathogenesis of atherosclerosis and cardiovascular complications among kidney
      allograft recipients.

PMID- 19100416
TI  - Therapeutic effect of Tripterygium wilfordii on proteinuria associated with
      sirolimus in renal transplant recipients.
AB  - Sirolimus (SRL) is a potent immunosuppressive drug used to prevent acute
      allograft rejection after renal transplantation. Nevertheless, the occurrence of
      proteinuria has recently been recognized among patients on SRL-based therapy. The
      aim of this study was to investigate the therapeutic effects of Tripterygium
      wilfordii Hook F. (T II) on proteinuria associated with SRL in renal transplant
      recipients. According to accepting T II, 36 recipients were divided into 2
      groups: T II group (n = 21) and valsartan group (n = 15). The T II group was
      administered 1 mg/kg/d, and the valsartan group, 80 mg twice per day for 12
      months. Efficiency was then evaluated. Complete remission: proteinuria decreased
      by >50%; partial remission: proteinuria decreased by 20% to 50%; ineffective:
      proteinuria decreased by <20%. Upon 12-month follow-up, the total effective rates
      in the T II group and the valsartan group were 95.2% and 86.7% (P < .05),
      respectively. Twenty of 21 patients with proteinuria in the T II group were
      negative at 3-month follow-up with disappearance of edema. There were some
      adverse events that had greater incidence rates in the valsartan group compared
      with the T II group, such as hyperkalemia (26.7% vs 4.8%). We concluded that the
      application of T II markedly reduced proteinuria associated with SRL in renal
      transplant patients.

PMID- 19100417
TI  - Toll-like receptor expression in patients with renal allograft dysfunction.
AB  - Toll-like receptor (TLR) is known to be a mediator of innate immunity, but recent
      reports have shown that TLR provides a link to adaptive immunity involved in
      allograft rejection. To explore the expression patterns in various conditions of
      renal transplantation, we examined TLR subunit mRNA expressions in renal
      allograft biopsies of acute rejection (AR; n = 11), chronic rejection (CR; n =
      15), chronic cyclosporine nephrotoxicity (CsAN; n = 22), and immunoglobulin A
      nephropathy (IgAN; n = 9) patients. Control tissues (n = 7) were obtained from
      normal renal cortical tissue of renal cell carcinoma patients. The diagnosis was
      made according to the Banff 97 classification. The expressions of TLR 2, 3, 4,
      and 9 mRNA were analyzed by real-time reverse transcriptase-polymerase chain
      reaction (RT-PCR) using SYBR green. Statistical analysis was performed using
      analysis of variance (ANOVA) and the Student t test. TLR 2 and 3 mRNA expressions
      were not significantly different in any group (P > .05). In contrast, TLR 4 mRNA
      expression was significantly increased in all allograft groups compared with that
      of controls, and significantly higher in the CsAN than other transplant groups (P
      < .05). TLR 9 mRNA expression was up-regulated in CsAN and IgAN compared with AR
      and CR (P < .05). These results suggested that TLR4 mRNA expression was increased
      in renal allograft patients with chronic allograft dysfunction. Further studies
      are needed to correlate TLR subtypes with various causes of graft dysfunction
      among renal allograft patients.

PMID- 19100418
TI  - Anemia after renal transplantation: an underestimated problem.
AB  - In end-stage renal disease patients anemia is known to be an independent risk
      factor for cardiovascular disease and death. In a monocenter retrospective
      analysis, we investigated 207 stable patients (68 women/139 men) who underwent a
      first renal transplantation. Immunosuppressive therapy was performed with either
      cyclosporine plus mycophenolate mofetil, tacrolimus plus mycophenolate mofetil,
      or rapamycin plus mycophenolate mofetil; 43.5% of the patients were treated with
      steroids. Seventy-eight patients (37.7%) displayed anemia, including 8.7% with a
      severe disorder displaying an average hemoglobin (Hb) level of <6.8 mmo/L in men
      and <6.2 mmol/L in women. In 8.2% of the cases, we observed moderate anemia (Hb
      6.8-7.4 mmol/L in men and 6.2-6.8 mmol/L in women), and in 20.8% (29 men and 14
      women), mild anemia (Hb <8.06 mmol/L in men and <7.45 mmol/L in women).
      Erythropoietin was administered in 55.5% of patients with severe anemia, 53% with
      moderate anemia, and 11.6% with mild anemia. Serum creatinine level was a
      significant predictor of anemia (B -0.004; SE 0.001; P < .01). Among patients
      with creatinine >200 micromol/L, 63% were anemic compared with 22% of those with
      a serum creatinine level <200 micromol/L (P < .05). No correlation was observed
      with immunosuppressive medication or treatment with angiotensin-converting enzyme
      inhibitors/angiotensin-II receptor antagonists. During a 3-year follow-up, both
      mortality and graft failure rates were significantly greater among anemic
      patients nonanemic patients (mortality 3.3% vs 0.5%, P < .001; graft failure 4.3%
      vs 0%, P < .001). We found an unexpectedly high incidence of anemia in patients
      with well-functioning grafts. Anemia as a risk factor for mortality and graft
      failure should be treated more intensively among renal transplant patients.

PMID- 19100419
TI  - Incidence of aspirin resistance and its relationship with cardiovascular risk
      factors and graft function in renal transplant recipients.
AB  - BACKGROUND: Aspirin (ASA) is frequently used to prevent cardiovascular events and
      improve renal graft function after renal transplantation. Clinical studies have
      demonstrated that decreased responsiveness to ASA therapy is associated with an
      increased risk of atherothrombotic events. However, no clinical trial to date has
      evaluated the incidence and clinical importance of ASA resistance among renal
      transplant recipients. AIM: To assess the incidence of ASA resistance and its
      association with cardiovascular risk factors (CRF) and renal graft function after
      renal transplantation. METHODS: We prospectively included 40 patients undergoing
      living related donor renal transplantation using ASA (80 mg/d) in the study. ASA
      resistance was defined using a platelet function analyzer (PFA-100). Glomerular
      filtration rate (GFR) was measured by postoperative Tc-99m
      diethylenetriaminepentaacetic acid renal scintigraphy. We investigated the
      incidence of ASA resistance and its relationship to CRF and renal graft function.
      RESULTS: ASA resistance was noted in 11 patients (27.5%). The demographic
      characteristics of the patients were similar in both groups (P > .05). Compared
      with patients in the ASA-sensitive group, patients in the ASA-resistant group
      showed significantly higher total cholesterol, low-density lipoprotein
      cholesterol, triglyceride, C-reactive protein, and fibrinogen levels and lower
      GFRs (44 +/- 21 mL/min vs 63 +/- 26 mL/min, P = .03). The incidence of ASA
      resistance was higher among patients with GFRs < 60 mL/min compared with those
      with a GFR >or= 60 mL/min (10% vs 1%; P = .012). CONCLUSION: ASA resistance is
      associated with higher lipid levels and inflammatory and thrombotic
      cardiovascular risk factors and lower GFRs in renal transplant recipients.

PMID- 19100420
TI  - Analysis of sexual function in kidney transplanted men.
AB  - INTRODUCTION: Sexual dysfunction among renal failure and kidney transplant
      patients remains controversial. The aim of this study was to evaluate sexual
      functions of men on hemodialysis compared with patients undergoing kidney
      transplantation. MATERIALS AND METHODS: Our study was based on 36 end-stage renal
      disease (ESRD) patients undergoing hemodialysis versus 32 kidney transplanted
      patients. A control group was composed of 23 healthy patients. The patients
      underwent an anamnesis, a physical examination, and the International Index of
      Erectile Function about sexual performance. Statistical analysis was performed by
      Student's t-test or the chi-square test with the level of significance set at P <
      .05. Data are reported as mean values +/- standard error of the means. RESULTS:
      The mean scores of the control, ESRD, and transplanted group were, respectively:
      for erectile function, 27.4 +/- 0.5, 22.4 +/- 1.3, 23.4 +/- 1.3; for orgasmic
      function, 9.5 +/- 0.1, 7.6 +/- 0.5, 8.9 +/- 0.5; for sexual desire function 9.4
      +/- 0.1, 7.1 +/- 0.3, 9.0 +/- 0.5; for intercourse satisfaction 12.8 +/- 0.3, 9.4
      +/- 0.7, 11.0 +/- 0.7; and for satisfaction related to sexual life 9.2 +/- 0.2,
      7.7 +/- 0.3, 8.6 +/- 0.6, proving that there were significant differences
      regarding orgasmic function, sexual desire, and intercourse satisfaction.
      CONCLUSION: It was possible to conclude from our study that kidney transplants do
      improve sexual function of patients with ESRD on hemodialysis.

PMID- 19100421
TI  - Ezetimibe in the treatment of uncontrolled hyperlipidemia in kidney transplant
      patients.
AB  - Dyslipidemia is an important complication affecting kidney transplant recipients.
      Statins, the first-line therapy, are often insufficient. Ezetimibe may be
      effective in combination with statin therapy. We performed a retrospective study
      to determine the safety and efficacy of ezetimibe treatment in addition to statin
      therapy among 27 stable renal transplant patients with uncontrolled
      hypercholesterolemia. We obtained fasting lipid profiles at 3 and 6 months before
      ezetimibe therapy, while the patients were receiving statins at maximum tolerated
      doses. Statin doses were stable during the study. All patients received ezetimibe
      (10 mg) once daily. Fasting lipid profile, kidney function, liver enzymes,
      creatine kinase, and immunosuppressive drug levels were obtained at baseline as
      well as at 3 and 6 months post-ezetimibe initiation. Combination therapy resulted
      in median reductions in total cholesterol of 29% (interquartile range [IQR] 12
      39; P = .0001) and 28% (IQR 9-38; P = .0001); in low-density lipoprotein
      cholesterol of 34% (IQR 16-61; P = .0001) and 44% (IQR 24-56; P = .0001); and in
      triglycerides of 14% (IQR 4-31; P = .01) and 19% (IQR 1-37; P = .006) at 3 and 6
      months post-ezetimibe therapy, respectively. There were no significant
      differences in high-density lipoprotein cholesterol, renal function, proteinuria,
      creatine kinase, amylase, liver function, body mass index, or drug levels. There
      were no adverse drug reactions that mandated treatment withdrawal. When combined
      with statin therapy ezetimibe seemed to be a safe and effective treatment for
      uncontrolled dyslipidemia among renal transplant patients.

PMID- 19100422
TI  - Alendronate is effective to treat bone loss in renal transplantation recipients.
AB  - Bone loss is a common complication among renal transplant patients. Some studies
      have shown that alendronate may be effective to treat bone loss in these
      patients. In this study, we have reported our experience with administration of
      alendronate to treat bone loss in renal transplanted patients. METHODS: The 46
      kidney transplant recipients with bone loss were randomly divided into 2 groups:
      group I was treated with calcium and calcitriol, and group II with calcium,
      calcitriol, and alendronate. We examined bone mineral density (BMD) and
      biochemical indicators of both groups. All patients received cyclosporine and
      prednisone treatment. RESULTS: There was no significant difference in age, body
      mass index, gender, immunosuppression, time since transplantation, 25(OH)D(3), or
      intact parathyroid hormone levels at study commencement. The BMD of the femoral
      neck was significantly increased (P < .05), and the serum type I collagen-cross
      linked N telopeptide (NTx) dramatically (P < .05) decreased in
      posttransplantation group II recipients treated with calcium, calcitriol, and
      alendronate. There were also significant differences in BMD and serum NTx between
      recipients treated with versus without alendronate (P < .05). CONCLUSION: At
      least in the short term, alendronate is a effective inhibitor for the treatment
      of bone loss in renal transplantation patients.

PMID- 19100423
TI  - Arm blood pressure index and lipoprotein(a) in renal transplant recipients.

PMID- 19100424
TI  - Human cytomegalovirus specific CD8(+) T lymphocytes display interferon-gamma
      secretion impairment in kidney transplant recipients with pp65 antigenemia.
AB  - Our study sought to investigate the immune response of cytotoxic T lymphocytes to
      human cytomegalovirus (HCMV) in kidney transplant recipients with virus
      reactivation. Nine kidney transplant recipients with serum HCMV immunoglobulin G
      and HLA-A 0201 genotype displayed HCMV pp65 antigenemia and were compared with 29
      control recipients who were free of antigenemia. The frequency of total HCMV
      specific cytotoxic T cells was determined using HLA-A2-NLVPMVATV-pentamer
      staining. The frequency of HCMV specific interferon (INF)-gamma secreting CD8(+)
      T cells was determined using intracellular INF-gamma staining after NLVPMVATV
      pulsing in vitro. The proportion of IFN-gamma secreting pentamer-stained CD8(+) T
      cells was calculated, representing the capacity for INF-gamma secretion among
      HCMV-specific CD8(+) T cells. We observed that the frequency of HCMV-specific
      pentamer-stained CD8(+) T cells and HCMV-specific IFN-gamma secreting CD8(+) T
      cells both remained unchanged, yet the proportion of IFN-gamma secreting CD8(+) T
      cells showed a significant difference between the 2 groups (39.2% +/- 17.2% vs
      20.0% +/- 13.3% respectively; P = .004), reflecting impaired IFN-gamma secreting
      capacity of HCMV-specific CD8(+) T cells among kidney transplant recipients
      displaying antigenemia, which may be a crucial reason for HCMV reactivation in
      immunosuppressed patients.

PMID- 19100425
TI  - The difference and the transition of indication for adult living donor liver
      transplantation between the West and the East.
AB  - In the last 10 years, adult living donor liver transplantation (ALDLT) has
      evolved in many countries of the world. Relative to cadaver liver
      transplantation, a living donor can curtail the time awaiting transplantation.
      However, the indication for ALDLT is still different between the West and the
      East. This article collects recent published literature on the indications for
      ALDLT in the West and East from 3 aspects: hepatocellular carcinoma (HCC),
      cirrhosis, and acute hepatic failure (AHF). The difference of ethics for ALDLT
      between the West and the East is also investigated. We sought to formulate the
      indications for ALDLT based upon the condition of our country and verified by
      ethical committees.

PMID- 19100426
TI  - Hepatopulmonary syndrome: morbidity and survival after liver transplantation.
AB  - Hepatopulmonary Syndrome (HPS) is a triad of liver disease, intrapulmonary
      vascular dilatation (IPVD), and arterial deoxygenation. Orthotopic liver
      transplantation (OLT) constitutes the only effective treatment; however, adverse
      outcomes have been reported. The aim of this study was to evaluate the early
      morbidity and short- and long-term survival after OLT for patients with and
      without HPS. We studied 59 transplant recipients divided into 2 groups: with HPS
      (HPS group n = 25) and without HPS (control group, n = 34) before the OLT. IPVD
      was diagnosed using transthoracic contrast-enhanced echocardiography. Arterial
      deoxygenation was defined as PA-a,O(2) >or= 15 mm Hg. The HPS and control groups
      were homogeneous regarding age (P = .36; 43.8 +/- 12.2 vs 46.9 +/- 13.5), gender
      (P = .47), male/female ratio (68%:32% and 78%:22%, respectively), and severity of
      liver disease. The PaO(2) was significantly lower (74.9 +/- 12.1 vs 93 +/- 6.4 mm
      Hg; P < .001) and the PA-a,O(2) was significantly higher in the HPS group (30.3
      +/- 10.6 vs 11.0 +/- 7.0; P < .001). The percentage of severe (n = 3) and very
      severe (n = 1) hypoxemia was 16%. There were no significant differences between
      HPS and control groups regarding short- (68% vs 77%; P = .27) and long-term
      survival (60% vs 64%; P = .67) as well as among patients with mild, moderate,
      severe, or very severe HPS and the control group (P = .53). Also, intensive care
      unit (ICU) stay (7.0 vs 5.5; P = .41), duration of mechanical ventilation (38.0
      vs 27.5; P = .43), reintubation rate (32.0% vs 23.5%; P = .45), and early
      postoperative complications (P = .72) were not different. In conclusion, there
      were no significant differences regarding the outcomes of OLT for patients with
      versus without HPS related to early morbidity or short- and long-term survival.

PMID- 19100427
TI  - Preliminary experience with indications for liver transplantation for
      hepatolithiasis.
AB  - OBJECTIVE: The aim of this study was to explore the indications for liver
      transplantation among patients with hepatolithiasis. PATIENTS AND METHODS: Data
      from 1,431 consecutive patients who underwent surgical treatment from January
      2000 to December 2006 were retrospectively collected for analysis. Surgical
      procedures included T-tube insertion combined with intraoperative cholangioscopic
      removal of intrahepatic stones, hepatectomy, cholangiojejunostomy, and liver
      transplantation. RESULTS: Nine hundred sixty-one patients who had a stone located
      in the left or right intrahepatic duct underwent hepatectomy or T-tube insertion
      combined with intraoperative cholangioscopic removal of intrahepatic stones. The
      rate of residual stones was 7.5%. Four hundred seventy patients who had a stone
      located in the bilateral intrahepatic ducts underwent surgical procedures other
      than liver transplantation; the rate of residual stones was 21.7%. Only 15
      patients with hepatolithiasis underwent liver transplantation; they all survived.
      According to the degree of biliary cirrhosis, recipients were divided into 2
      groups: a group with biliary decompensated cirrhosis (n = 7), or group with
      compensated cirrhosis or no cirrhosis (n = 8). There were significant differences
      in operative times, transfusion volumes, and blood losses between the 2 groups (P
      < .05). In the first group, 6 of 7 patients experienced surgical complications,
      and in the second, 8 recipients recovered smoothly with no complications. Health
      status, disability, and psychological wellness of all recipients (n = 15) were
      significantly improved at 1 year after transplantation compared with
      pretransplantation (P < .05). CONCLUSIONS: Liver transplantation is a possible
      method to address hepatolithiasis and secondary decompensated biliary cirrhosis
      or difficult to remove, diffusely distributed intrahepatic duct stones
      unavailable by hepatectomy, cholangiojejunostomy, and choledochoscopy.

PMID- 19100428
TI  - Radiofrequency-assisted liver resection in patients with hepatocellular carcinoma
      and cirrhosis: preliminary results.
AB  - Radiofrequency (RF)-assisted liver resection has been shown to allow virtually
      bloodless procedures without the need for vascular exclusion maneuvers. The aim
      of this study was to evaluate the safety and feasibility of RF-assisted liver
      resection in cirrhotic patients with hepatocellular carcinoma (HCC) and,
      moreover, to assess whether the RF-assisted procedure influenced the outcomes in
      terms of morbidity and mortality. This retrospective study included 39 cirrhotic
      patients who underwent RF-assisted liver resection for HCC between September 2001
      and March 2006. In this period, we performed 17 monosegmentectomies, 16
      bisegmentectomies, 4 trisegmentectomies, and 2 right hepatectomies. We never
      performed vascular exclusion maneuvers. Blood transfusion was necessary in 3
      cases. One patient died postoperatively because of untreatable hepatorenal
      syndrome. The morbidity rate was 23%. Among patients without postoperative
      morbidity (n = 30), the 4-year survival rate was 61% versus 23% in patients who
      experienced postoperative morbidity (n = 9; P < .05). The 4-year disease-free
      survival rate was 40% in patients without postoperative morbidity versus 10% in
      patients who experienced postoperative morbidity (P = .05). Tumor dimension,
      number of lesions, and Child-Pugh class at surgery did not seem to significantly
      influence the 4-year overall survival (P > .05). In conclusion, RF-assisted liver
      resection was a safe, feasible procedure associated with low morbidity and
      hospital mortality rates even in cases of liver cirrhosis. It is, in our opinion,
      highly recommended for patients with HCC not suitable for liver transplantation.

PMID- 19100429
TI  - Liver failure and the need for transplantation in three patients with
      hepatoportal sclerosis.
AB  - Hepatoportal sclerosis (HPS) is one of the causes of noncirrhotic portal
      hypertension. In most patients, hepatic synthetic dysfunction does not occur;
      rarely they may require liver transplantation. In this study, we have reported
      the clinicopathologic characteristics of 3 patients diagnosed with HPS after
      examination of the explanted liver. Small liver volume, significant portal
      fibrosis, and phlebosclerosis may contribute to hepatic synthetic dysfunction in
      patients with HPS.

PMID- 19100430
TI  - Laparoscopic hepatectomy for a modified right graft in adult-to-adult living
      donor liver transplantation.
AB  - BACKGROUND: We performed a modified right hepatectomy completely by laparoscopic
      techniques preserving the middle hepatic vein (MHV) branches in adult-to-adult
      living donor liver transplantation (LDLT). PATIENTS AND METHODS: Two young women
      (24 and 25 years old) volunteered to be live donors for their parents who had
      hepatocellular carcinomas. As the donors expressed concerns about scarring, we
      performed a laparoscopic procedure using a hand port device. Mobilization of the
      right liver and the hepatic parenchymal transection were performed under
      pneumoperitoneum. Parenchymal transection was performed using a laparoscopic
      ultrasonic aspirator without the Pringle maneuver. During parenchymal
      transection, major MHV branches >5 mm were preserved using Hem-o-lock clips. The
      graft was extracted through the hand port site. On the back table, the 3 MHV
      branches were reconstructed using an artificial vascular graft. The livers were
      transplanted without complications. RESULTS: The operative times for the donors
      were 765 and 898 minutes. The donors did not require transfusions or reoperation;
      they were discharged on postoperative days 10 and 14 with normal liver functions.
      CONCLUSION: A hepatectomy performed completely by laparoscopic techniques for a
      right graft with preservation of the MHV branches was technically feasible.

PMID- 19100431
TI  - Median arcuate ligament in orthotopic liver transplantation: relevance to
      arterial reconstruction.
AB  - Median arcuate ligament (MAL) syndrome results from luminal narrowing of the
      celiac artery by the insertion of the diaphragmatic muscle fibers or by fibrous
      bands of the celiac nervous plexus. In 10% to 50% of cases it is responsible for
      significant angiographic celiac trunk compression. In orthotopic liver
      transplantation (OLT), the presence of celiac compression by MAL is considered to
      be a risk factor for hepatic arterial thrombosis (HAT); it may lead to graft
      loss. Various surgical procedures have been proposed to overcome the impact of
      MAL in OLT, but their impact is still ill defined. The aim of our study was to
      compare standard hepatic artery reconstruction and graft reconstruction
      (aortohepatic bypass) in terms of HAT among patients with MAL undergoing OLT. We
      retrospectively reviewed 168 adult recipients of OLT performed from January 1991
      to December 1998. Ten cases (5.6%) of celiac compression by MAL were identified
      after celiomesenteric arteriography. There was no significant difference in terms
      of HAT incidence when aortohepatic bypass was performed compared to a standard
      anastomosis; moreover, this was greater in the graft reconstruction group (25% vs
      17%; P = .67). In our opinion, the presence of an arcuate ligament should not
      contraindicate a routine hepatic artery reconstruction.

PMID- 19100432
TI  - Estimation of standard liver volume for liver transplantation in the Chinese
      population.
AB  - INTRODUCTION: The accurate assessment of standard liver volume (SLV) is necessary
      for the safety of both the donor and the recipient in living donor liver
      transplantation. However, the accuracy of SLV formulas relates to cohorts or
      races. This study examined the accuracy of a simple linear formula versus
      previous formulas of SLV for Chinese adults. METHODS: Among 112 patients with
      normal liver, we created a new formula for SLV with stepwise regression analysis
      using the following variables: age, gender, body weight, body height, body mass
      index, and body surface area. The agreement between the actual liver volume (LV)
      and calculated LV using various formulas was prospectively evaluated among 63
      living donors by paired-sample student's t-test and Lin's concordance correlation
      coefficient. RESULTS: A new formula was developed SLV (mL) = 949.7 x BSA (m(2)) -
      48.3 x age - 247.4 where age was counted as 1 for those <40, 2 if 41-60, and 3 if
      >60 years old. The calculated LV using our formula showed no significant
      difference from the actual LV using the paired-samples student's t-test (P =
      .653). Lin's concordance correlation coefficient showed substantial agreement
      between estimated LV using our formula and actual LV. Furthermore, this study
      also observed an almost perfect agreement between our formula and the Yoshizumi
      et al formula. CONCLUSION: Our formula, which accurately estimated LV among
      Chinese adults, may be applicable to adults of other ethnicitis.

PMID- 19100433
TI  - Open abdomen management with human acellular dermal matrix in liver transplant
      recipients.
AB  - BACKGROUND: Abdominal wall closure after liver transplantation is not always
      feasible and may result in increased intra-abdominal pressure along with
      associated complications. Various temporary closure techniques as well as open
      wound management have been used to address this complex problem. The aim of this
      series was to describe an approach to definitive wound closure of the open
      abdomen in liver transplant patients. METHODS: We performed a retrospective
      review of all liver transplant patients at our institution from September 2005 to
      November 2007. The management of the open abdomen in 10 liver transplant patients
      was reviewed, and a novel approach described to manage these defects. RESULTS:
      Ten patients with open wounds were closed during the study period using human
      acellular dermal matrix (HADM). There were 7 men and 3 women of median age 55
      years. Average size of HADM was 235 cm(2). The median follow-up is 10 months with
      no incidence of evisceration or hernia. In 1 patient, the graft failed along the
      lateral side due to infection; it dislodged during vacuum-assisted closure
      dressing change in another patient at 5 months after closure. Fascial closure was
      not possible due to organ edema (n = 3), a large liver (n = 4) or wound infection
      with dehiscence (n = 3). CONCLUSIONS: HADM can be used for primary wound closure
      in both clean and contaminated wounds as an alternative to an open abdomen post
      liver transplantation.

PMID- 19100434
TI  - Continuous versus interrupted suture for hepatic artery anastomosis in liver
      transplantation: differences in the incidence of hepatic artery thrombosis.
AB  - BACKGROUND: Hepatic artery thrombosis (HAT) is a serious complication after
      orthotopic liver transplantation (OLT) and remains a significant cause of graft
      loss. HAT following OLT has been reported in 3% to 9% of patients. Among the
      surgical factors considered to be associated with HAT, arterial reconstruction
      might be the most important. The goal of this study was to compare the incidence
      of HAT between interrupted suture (IS) and continuous suture (CS) techniques
      during hepatic artery reconstruction in liver transplantation. METHODS: We
      performed a retrospective analysis of 200 consecutive liver transplantations
      occurring between May 2002 and December 2006, including medical records for: age,
      gender, cold ischemic time, warm ischemic time, type and number of arterial
      anastomosis. Hepatic artery anastomoses were performed using a 7-0 prolene with a
      running CS in the first 105 patients (CS group), and with an IS in the last 95
      patients (IS group). RESULTS: Statistical analysis of age, gender, cold and warm
      ischemia time, and number of hepatic artery anastomoses was not different between
      the CS and IS groups. Eleven episodes of HAT were identified in the CS group
      (10%) and two episodes (2%) in the IS cohort, a significant difference (P =
      .0173). CONCLUSIONS: Our results suggested that IS might be a better choice for
      hepatic artery anastomosis with a lower incidence of HAT.

PMID- 19100435
TI  - Sirolimus-based immunosuppression therapy in liver transplantation for patients
      with hepatocellular carcinoma exceeding the Milan criteria.
AB  - AIM: Sirolimus (SRL) acts as a primary immunosuppressant or antitumor agent. The
      aim of the present study was to evaluate the influence of SRL on the recurrence
      rate and survival of patients after orthotopic liver transplantation (OLT) for
      hepatocellular carcinoma (HCC) exceeding the Milan criteria. MATERIALS AND
      METHODS: We retrospectively examined 73 consecutive patients who underwent OLT
      for HCC exceeding the Milan criteria from March 2004 through December 2005. Among
      them, 27 patients were treated with SRL-based immunosuppressive protocols after
      OLT, and 46 patients by an FK506-based protocol. Statistical analysis was based
      on the intent-to-treat method. RESULTS: The 2 groups were comparable in all
      clinicopathologic parameters. The mean overall survival was 594 +/- 35 days in
      the SRL group and 480 +/- 42 days in the FK506 group (P = .011); the mean disease
      free survival period was 519 +/- 43 days in the SRL group and 477 +/- 48 days in
      the FK506 group (P = .234). Multivariate analysis revealed Child's status (P =
      .004) and immunosuppressive protocol (P = .015) were the significant factors
      affecting overall survival. Only microvascular invasion (P = .004) was
      significantly associated with disease-free survival. Among 24 surviving patient
      in the SRL group, 2 patients had SRL discontinued for toxicity; 10 had SRL
      monotherapy immunosuppression. CONCLUSION: The SRL-based immunosuppressive
      protocol improved the overall survival of patients after OLT for HCC exceeding
      the Milan criteria, probably by postponing recurrence and with better
      tolerability.

PMID- 19100436
TI  - Influence of coronary artery disease on outcomes after liver transplantation.
AB  - Patients with coronary artery disease (CAD) who undergo liver transplantation
      (OLT) have been previously identified as a high-risk group. Since that
      identification, the management of CAD has undergone significant changes as has
      the cardiovascular screening and selection of patients for OLT. We
      retrospectively identified 42 patients with known CAD who underwent OLT to
      compare outcomes with a control group of 42 patients without CAD who were matched
      for gender, age, and primary liver disease. Mortality rates were higher in the
      CAD than the control group at 1 year (5 vs 1) and 3 years (11 vs 3; P < .05)
      although lower than previously reported (at 3 years, 26% vs 50%). New
      cardiovascular morbidity was also more frequent among the CAD than control group
      at 1 year (11 vs 3; P < .05) and 3 years (16 vs 4; P < .05). Although outcomes
      for patients with CAD undergoing OLT are improved from historical levels, they
      are still worse than those in patients without CAD despite current management and
      selection strategies.

PMID- 19100437
TI  - Salvage liver transplantation for recurrent hepatocellular carcinoma after liver
      resection: feasibility of the Milan criteria and operative risk.
AB  - INTRODUCTION: Although the Milan criteria are widely accepted for liver
      transplantation (OLT) for hepatocellular carcinoma (HCC), they have not been
      fully evaluated as feasible for salvage liver transplantation (SLT) of recurrent
      HCC after hepatic resection. The operative difficulties of SLT increase the
      operative risk. The aim of this study was to evaluate the feasibility of the
      Milan criteria for SLT and its operative complications. PATIENTS AND METHODS:
      From March 2005 to November 2007, 46 HCC patients received OLT including 15 SLTs
      after prior partial hepatectomy (SLT group) and 31 primary OLTs (PLT group).
      RESULTS: There was no postsurgical hospital mortality among the SLT group but one
      case in the PLT group due to pneumonia followed by sepsis. There was no
      difference in the incidence of surgical complications between the two groups.
      Overall survival rates of SLT group patients were similar to those of the PLT
      group (P = .14), especially comparing both groups of patients within the Milan
      criteria (P = .89). There was no recurrence of HCC among the patients within the
      Milan criteria. CONCLUSIONS: SLT is a feasible procedure for recurrent HCC
      meeting the Milan criteria; the operative risk of the SLT is also acceptable.

PMID- 19100438
TI  - Biological changes after liver transplantation according to the presence or not
      of graft steatosis.
AB  - AIM: To assess the consequences of graft steatosis on postoperative liver
      function as compared with normal liver grafts. PATIENTS AND METHODS: From January
      2005 to December 2007, liver transplant patients were prospectively included,
      excluding those who experienced arterial or biliary complications or presented
      acute rejection. All patients had a surgical biopsy after reperfusion. Patients
      were compared according to the rate of macrovacuolar steatosis: namely above or
      below 20%. RESULTS: Fifty-three patients were included: 10 in the steatosis group
      and 43 in the control group. No significant difference was observed in terms of
      morbidity, mortality, and primary non- or poor function. Nevertheless, biological
      changes after the procedure were significantly different during the first
      postoperative week. Prothrombin time, serum bilirubin, and transaminases were
      significantly increased among the steatosis group compared with the control group
      (P < .05). CONCLUSION: This case-controlled study including a small number of
      patients, described postoperative biological changes among liver transplantations
      with steatosis in the graft.

PMID- 19100439
TI  - Primary nonfunction in liver transplantation: a single-center experience.
AB  - Primary nonfunction (PNF) after liver transplantation is life threatening. In
      recent review of data from Scientific Registry of Transplant Recipients on liver
      transplantations between 2002 and 2004, the rate of PNF was 5.8%. In this study,
      our aim was to review the incidence and outcome of PNF at our transplant center.
      From February 1998 through December 2007, 1679 liver transplants were performed.
      There were 24 PNF (1.4%) in 22 patients. The 6- and 12-month patient survival
      rates were 72.2% and 63.3%, respectively. Our results demonstrate a low incidence
      of PNF at our center. However, the patient survival outcome remains poor. Future
      investigations to improve survival among liver transplant recipients with PNF are
      essential.

PMID- 19100440
TI  - Liver transplantation for biliary atresia in Taiwan: a national study.
AB  - A national database for orthotopic liver transplantation (OLT) among biliary
      atresia (BA) cases in Taiwan has not been reported. Using the National Health
      Insurance (NHI) database to investigate the prognostic features of patients with
      BA receiving OLT, we studied the prognosis of this procedure for BA. The NHI in
      Taiwan covers most of the population (>99%). From 1996-2004, 106 BA patients
      underwent transplantation. A linear time trend analysis was performed to estimate
      the annual slope for BA patients to receive OLT. The rate of increase per year of
      2.6 cases was significant (R(2) = .649; P = .029). The 5-year overall survival
      after OLT was 97.1% +/- 1.6%, which was not different between those who had or
      had not previously undergone portoenterostomy (94.9% vs 97.8%; P = .160). It was
      not different among patients undergoing transplantation during the various
      seasons (P = .505). Our data confirmed the effectiveness of OLT for the treatment
      of BA in children with or without KP in Taiwan.

PMID- 19100441
TI  - Favorable outcome of orthotopic liver transplantation in very high-risk
      situations.
AB  - BACKGROUND: Favorable outcomes of marginal liver grafts depends on optimal
      perioperative control and good recipient parameters. The aim of this study was to
      assess the results of marginal liver grafts associated with prolonged ischemic
      times and high-risk recipients. METHODS: We retrospectively reviewed data from
      patients who underwent orthotopic liver transplantation between 2001 and 2005.
      The patients were divided into two groups: group 1 received marginal liver grafts
      with ischemia times >or= 12 hours and recipient United Network for Organ Sharing
      (UNOS) status 1, 2A, and 2B. Patients who had marginal liver grafts with ischemic
      times less than 12 hours and/or better UNOS status were classified as group 2. We
      compared initial graft function as well as patient and graft survivals at 1 year
      between the two groups. RESULTS: Among 31 patients who were reviewed, four were
      excluded because of incomplete data and 24/27 received marginal liver grafts.
      Seven patients were classified into group 1, and 17 into group 2. The initial
      poor function rate was 85.7% (6/7 patients) and 76.47% (13/17 patients) in groups
      1 and 2, respectively. The 1-year survival rate in group 1 was 85.7% (6/7
      patients) and 94.12% (16/17 patients) in group 2. CONCLUSION: Marginal liver
      grafts can be used with favorable outcomes even in high-risk situations, such as
      prolonged ischemia times and high-risk recipients.

PMID- 19100442
TI  - Expression of matrix metalloproteinases 2 and 9 in donor liver, cirrhotic liver,
      and acute rejection after human liver transplantation.
AB  - Matrix proteinases are known to play an important role in the cell migration
      during cancer invasion, in organ development, and in tissue damage during
      inflammatory process. Among the matrix proteinases, matrix metalloproteinases
      (MMP) are the most powerful proteinases. Changes at the extracellular matrix
      components play an essential role in acute rejection after orthotopic liver
      transplantation (OLT). This prospective clinical study investigated the
      alterations in the expression of MMP-2 (72-kd gelatinase type IV collagenase
      [gelatinase A]) and MMP-9 (92-kd gelatinase type IV collagenase [gelatinase B])
      in patients with acute cellular rejection (ACR) compared with the biopsies of
      cirrhotic livers (CL) of patients who underwent OLT, and with healthy livers (HL)
      of the donors. Although MMP-2 expression was not present in the hepatocytes of
      the HL, it was in the endothelium; it was moderate in CL and severe in the livers
      suffering from ACR. MMP-9 expression, on the other hand, is found to be present
      only in the inflammatory cells, with an increasing intensity in HL, CL, and in
      livers suffering from ACR. The results suggest that MMP-2 and MMP-9, beside their
      roles in liver injury with tissue remodeling and fibrosis as mentioned in the
      previous studies, can be a marker of acute rejection.

PMID- 19100443
TI  - Simultaneous monitoring by real-time polymerase chain reaction of epstein-barr
      virus, human cytomegalovirus, and human herpesvirus-6 in juvenile and adult liver
      transplant recipients.
AB  - Cytomegalovirus (CMV), Epstein-Barr virus (EBV), and human herpesvirus-6 (HHV-6)
      cause symptomatic diseases in liver transplant recipients. The loads of these
      viruses, the associations between viral DNAemia, serologic status, and acute
      rejection reactions were investigated in a group of 17 juvenile and 17 adult
      recipients of living donor liver transplantation (LDLT) for a median of 8 weeks
      posttransplantation. At least 1 plasma sample from 15/34 (44.1%) patients was
      positive for CMV DNA. For most of the CMV-positive patients, the CMV DNA appeared
      in the second week of LDLT, and disappeared by the eighth week. A minimum of 200
      EBV DNA copies/mug peripheral blood mononuclear cell DNA (defined as positive for
      EBV) was detected in 5/34 (14.7%) patients, and the number of EBV-positive
      children was significantly greater than the number of EBV-positive adults. In
      most of the EBV-positive patients, the EBV loads increased after 4 weeks
      posttransplantation. Plasma HHV-6 was detected in 7/34 (20.6%) patients. HHV-6
      DNA appeared for a short period from the second week of LDLT. In addition, 8 of
      the 19 virus-positive recipients carried 2 viruses, with the combination of CMV
      and HHV-6 being the most frequent. Serologic status seemed to be an important
      factor for all 3 viral infections. The rate of acute cellular rejection was not
      significantly higher in the CMV-, EBV-, or HHV-6-positive groups. Simultaneous
      monitoring for 3 herpesviruses revealed the impact of these viruses on LDLT
      recipients.

PMID- 19100444
TI  - Pulmonary interstitial and vascular abnormalities following cardiac
      transplantation.
AB  - Impairment of pulmonary diffusion (KCO) is frequently seen in patients following
      orthotopic heart transplantation (HTX). To assess potential histomorphological
      pulmonary causes of KCO abnormalities, we evaluated tissue samples from 73
      patients who succumbed after HTX in the presence of KCO abnormalities, excluding
      those with infectious or primary pulmonary causes of death. In 97% of subjects,
      we observed considerable histomorphological changes in interstitial or vascular
      tissue or both. In 32% of samples, interstitial changes (eg, cell proliferation
      or fibrosis) were accompanied by vascular abnormalities, whereas more than two
      thirds of the patients showed alterations in one of the two conditions.
      Hemosiderin-laden macrophages were observed in 48% of subjects. The mean alveolar
      capillary wall thickness was significantly increased to 9.9 +/- 4.2 mum. The time
      of survival after HTX was not correlated with the incidence of pathological
      findings. The described vascular and interstitial pulmonary changes as well as
      the increased membrane thickness may cause the persistent impairment of KCO after
      HTX.

PMID- 19100445
TI  - Ocular complications of heart transplantation in a Chinese population.
AB  - The purpose of this study was to investigate ocular complications among a group
      of patients on long-term, high-dose immunosuppression and corticosteroids for the
      maintenance of orthotopic heart transplants. Additionally, we provided
      information pertinent for the early diagnosis and treatment of eye diseases. In
      this study, we retrospectively assessed the clinical data of 138 patients with
      orthotopic heart transplantations from May 2000 to October 2005, including
      assessment of ophthalmic symptoms and signs, as well as the general condition,
      treatment, and prognosis. Of 138 transplant recipients examined (276 eyes), 47
      eyes (17.0%) showed ocular surface diseases. Sixty-four (23.2%) had a posterior
      subcapsular cataract, and 16 (5.8%) corticosteroid glaucoma. Fifteen (5.6%) had
      ocular fundus diseases. Various ocular complications related to immunosuppression
      and corticosteroids appear among heart transplant patients. Cardiac surgeons and
      ophthalmologists must closely evaluate ocular symptoms in the posttransplantation
      period.

PMID- 19100446
TI  - Single-lung transplantation for cystic fibrosis and metachronus pneumonectomy:
      case reports.
AB  - Three patients with end-stage cystic fibrosis (CF) underwent single lung
      transplantation (SLT) with contralateral pneumonectomy. In the first case,
      contralateral pneumonectomy (CP) was performed before SLT. The patient is alive
      with no signs of infection or rejection. For the other 2 cases, CP was performed
      after SLT. One patient died 8 months later with septicemia; the other patient
      died after 10 days because of complicated bronchopleural fistula and infection of
      the pneumonectomy space. SLT can be a good option for some patients with CF. The
      outcome is good when CP is done before SLT. However, CP must be done
      simultaneously with SLTX.

PMID- 19100447
TI  - Extracorporeal membrane oxygenation for primary allograft failure.
AB  - OBJECTIVE: Herein we have reported our experience concerning the usefulness of
      extracorporeal membrane oxygenation (ECMO) in heart transplant patients. PATIENTS
      AND METHODS: Between July 2002 and March 2007, 11 heart transplant patients,
      namely, 8 men and 3 women of overall mean age of 49.4 +/- 13.9 years (range, 19
      62 years) with primary graft failure underwent ECMO implantation. Two patients
      had pulmonary hypertension; 3 had been transplanted with hearts from marginal
      donors. At the time of implantation, all were in severe cardiogenic shock despite
      maximal inotropic support. In 6 patients, the ECMO was implanted centrally in the
      operating room when there was failure of weaning of cardiopulmonary bypass. Among
      the 5 remaining patients, ECMO was implanted peripherally in the intensive care
      unit, during the first 60 hours, including 3 cases of hemodynamic instability and
      1 of irreversible cardiac graft arrest. The last patient was implanted on day 30
      after transplantation because of acute rejection. RESULTS: Mean pump outflow was
      2.7 +/- 0.4 L/min/m(2). One patient died on circulatory support due to a cerebral
      hemorrhage. Ten patients were weaned from ECMO after a mean duration of 9.1 +/-
      6.9 days (range, 1-18 days). All of them were successfully discharged. No
      retransplantation occurred. CONCLUSION: Rapid operating room or bedside placement
      of ECMO allowed stabilization of hemodynamics with potential myocardial recovery
      in patients with cardiac graft failure.

PMID- 19100448
TI  - Conversion to sirolimus in kidney-pancreas and pancreas transplantation.
AB  - Reports on the use of sirolimus (SRL) in pancreas transplantation are still
      limited. The aim of this study was to evaluate the outcome of SRL conversion in
      pancreas transplant patients. Among 247 patients undergoing simultaneous kidney
      pancreas or solitary pancreas transplantation, 33 (13%) were converted to SRL.
      The reasons for conversion were calcineurin inhibitors (CNI) nephrotoxicity (n =
      24; 73%), severe neurotoxicity owing to CNI (n = 1; 3%), severe and/or recurrent
      acute rejection episodes (n = 7; 21%), gastrointestinal (GI) side effects of
      mycophenolate mofetil (MMF; n = 5; 15%), and hyperglycemia (n = 4; 12%). Before
      conversion, all patients were maintained on a CNI, MMF, and low-dose steroids.
      They were gradually converted to SRL associated with either CNI or MMF
      withdrawal. Sixty-three percent (n = 15) of patients who were converted owing to
      CNI nephrotoxicity, showed stable or improved renal function. At 12 months after
      conversion, serum creatinine levels were significantly decreased in this group
      (2.2 +/- 0.5 vs 1.6 +/- 0.3 mg/dL; P = .001) and C-peptide values increased (2.9
      +/- 1.1.1 vs 3.1 +/- 1.3 nmol/L; P = .018). The only patient with
      leucoencephalopathy showed improved neurologic status after SRL conversion. All
      patients converted to SRL because of GI side effects of MMF showed improvements,
      and none of those converted because of hyperglycemia experienced improvement.
      There were no episodes of acute rejection after conversion. We concluded that
      conversion to SRL in pancreas transplantation should be considered an important
      alternative strategy, particularly for CNI nephrotoxicity and neurotoxicity, and
      in cases of severe diarrhea due to MMF.

PMID- 19100449
TI  - Influence of a donor quality score on pancreas transplant survival in the
      Eurotransplant area.

PMID- 19100450
TI  - Orthotopic kidney retransplantation in simultaneous pancreas kidney transplant
      patients with renal failure.
AB  - Traditionally transplant nephrectomy was required as a separate procedure prior
      to retransplantation in simultaneous pancreas kidney transplant patients. An
      alternative approach combining both procedures is described, during which the
      rejected kidney is removed and replaced orthotopically by the new allograft.

PMID- 19100451
TI  - Modified method for isolation of langerhans islets from mice.
AB  - Successful isolation of Langerhans islets is a crucial prerequisite for their
      experimental or possible clinical use such as transplantation. Centrifugation in
      a Ficoll gradient is a common step used for separation of Langerhans islets from
      exocrine tissue. However, islets have been reported to be negatively affected by
      employing Ficoll gradients. Therefore, the aim of this study was to modify the
      isolation procedure by excluding Ficoll gradient centrifugation to obtain a
      similar or better yield of viable, functional islets. In our modification of the
      isolation procedure, the separation of islets from exocrine tissue was based on
      their sedimentation rate combined with their differential ability to attach to
      the surface of culture dishes for suspension cells. The resulting purity of
      islets facilitated their handpicking from the suspension. The mean yield was 900
      viable, insulin-producing islets per mouse, which was comparable to or even
      higher than the yield in commonly used protocols. Our modification of the
      isolation method may be useful when centrifugation in Ficoll gradient is
      undesirable due to potential toxicity.

PMID- 19100452
TI  - Liposome-mediated transfer can improve the efficacy of islet labeling with
      superparamagnetic iron oxide.
AB  - An in vivo method for islet visualization using magnetic resonance imaging (MRI),
      using superparamagnetic iron oxide (SPIO), has been described. Herein we have
      developed a protocol that uses cationic liposomes to increase the efficiency of
      islet cell labeling by SPIO in vitro. Fresh islet cells were incubated in RPMI
      1640 medium, to which had been added a range of concentrations of ferucarbotran,
      a SPIO contrast agent. At each SPIO concentration, duplicate samples were
      incubated with versus without addition of cationic liposomes. We measured
      intracellular iron concentration, cell viability, and insulin-release function
      after labeling. We observed that the amount of iron bound to islet cells
      increased as the concentration of added SPIO increased. The presence of liposomes
      increased labeling efficiency at each SPIO concentration. In vitro MRI confirmed
      the effect of liposomes to improve labeling efficiency of islet cells by SPIO.

PMID- 19100454
TI  - Chitosan/gelatin hydrogel prolonged the function of insulinoma/agarose
      microspheres in vivo during xenogenic transplantation.
AB  - PURPOSE: A chitosan/gelatin solution with glycerol 2-phosphate disodium salt
      hydrate in liquid phase at room temperature becomes a hydrogel at 37 degrees C.
      The material can be used as an injectable cell carrier into the human body for
      gelation in situ. We hoped that the chitosan/gelatin hydrogel provided extra
      protection for insulinoma/agarose microspheres during xenogenic transplantation.
      MATERIALS AND METHODS: Mouse insulinoma was microencapsulated in agarose as
      microspheres, which were macroencapsulated in chitosan/gelatin hydrogel. Insulin
      secreting profiles were first demonstrated in vitro. Diabetic rats were injected
      subcutaneously with insulinoma/agarose microspheres or insulinoma/agarose
      microspheres suspended in chitosan/gelatin solution. The nonfasting blood glucose
      concentrations (NFBG) of diabetic rats were measured perioperatively. Rats were
      humanely killed 1 month postoperatively and the hydrogel was retrieved for
      histological examination. RESULTS: The insulinoma/agarose microspheres
      continually secreted insulin for 1 month when macroencapsulated in
      chitosan/gelatin hydrogel in vitro. The NFBG of diabetic rats injected with
      insulinoma/agarose microspheres decreased to euglycemic status albeit
      hyperglycemia was restored within 10 days. The NFBG of diabetic rats injected
      with chitosan/gelatin hydrogel, which contained insulinoma/agarose microspheres,
      was maintained at less than 200 mg/dL for 25 days. The histological section
      revealed immune cell infiltration and accumulation within the hydrogel and around
      the iusulinoma/agarose microspheres that may have contributed to the slowly
      increasing NFBG after day 25. CONCLUSION: This study showed that chitosan/gelatin
      hydrogel can be used as a cell carrier for an injectable bioartificial pancreas;
      the hydrogel prolonged the function of cells encapsulated in agarose microspheres
      during xenogenic transplantation.

PMID- 19100453
TI  - Hemosiderin deposits confounds tracking of iron-oxide-labeled stem cells: an
      experimental study.
AB  - BACKGROUND: The aim of the present research was to study the possible
      interference of hemosiderin deposits with the histological detection of dextran
      coated, iron-labeled, mesenchymal stem cells after intracoronary administration
      in a porcine model of myocardial infarction. MATERIALS AND METHODS: A myocardial
      infarction was induced in six animals that received intracoronary iron-labeled
      autologous mesenchymal stem cells (group 1; n = 2) or placebo (group 2; n = 4).
      Six control animals without myocardial infarction underwent direct
      intramyocardial injections of iron-labeled autologous mesenchymal stem cells
      (group 3; n = 2) or placebo (group 4; n = 4). Histological sections from
      explanted hearts were stained with Prussian blue to identify dextran-coated, iron
      labeled, mesenchymal stem cells. RESULTS: After Prussian blue staining, granular
      blue labeling in the tissue was observed in both groups of animals with infarcts.
      Similar granular blue labeling was detected in hearts from control animals
      without infarction that had received iron-labeled mesenchymal stem cells.
      However, hearts from control animals without infarction that received placebo did
      not have any granular blue labeling in the tissue. CONCLUSIONS: Hemosiderin from
      infarction hemorrhage interferes with detection of dextran-coated iron-labeled
      mesenchymal stem cells after intracoronary administration, suggesting that this
      marker is not useful to detect mesenchymal stem cells in a porcine model of
      myocardial infarction.

PMID- 19100455
TI  - Living-related small bowel transplantation for three patients with short gut
      syndrome.
AB  - OBJECTIVE: We summarized our experience of living-related small bowel
      transplantation and postoperative management of 3 patients with short gut
      syndrome. METHODS: Patient #1, an 18-year-old boy, received a 150-cm segment of
      distal ileum with a vascular pedicle of distal superior mesenteric artery and
      vein, which was donated by his father. Patient #2, a 15-year-old boy, received a
      160-cm graft of distal ileum from his mother. Patient #3, a 17-year-old boy,
      received a 170-cm graft of distal ileum from his father. The graft artery and
      vein were anastomosed to the recipient infrarenal aorta and vena cava,
      respectively, in end-to-side fashion using 7/0 Prolene suture. Intestinal
      continuity was restored by anastomosis of proximal end of the graft to the
      recipients' own proximal jejunum, the distal end was left open as a stoma. The
      recipient distal gut was anastomosed to the distal end of the graft. All 3
      recipients were given FK506 (tacrolimus) regularly combined with periodic
      mycophenolate mofetil. In cases of acute rejection, large doses of steroids were
      administered to the recipients. RESULTS: The recipients and donors had fairly
      unremarkable postoperative courses. So far, patient #1 has survived for 7 years
      and 6 months with a well-functioning graft and without requirement for total
      parenteral nutrition (TPN) support. His body weight increased 20 kg and of his
      life quality has dramatically improved. Patient #2, however, died of acute
      rejection with fatal sepsis at 5 months after transplantation. Patient #3 has
      survived for 3 years and 8 months enjoying a normal life. Postoperative recovery
      of all 3 donors was unremarkable. They were discharged 12 days after surgery
      without complications. CONCLUSION: Outcomes of the implantation using the distal
      ileum as a graft in living-related small bowel transplantation have been
      satisfactory for both recipients and donors. It is feasible to anastomose the
      graft artery and vein to the recipient infrarenal aorta and vena cava. The
      intestinal continuity can be restored by a 1-stage strategy with minimal risk to
      the recipient. Appropriate application and adjustment of immune suppressors are
      crucial for the recipients to experience high-quality lives.

PMID- 19100456
TI  - Myeloablative cord blood transplantation for adults with hematological
      malignancies using tacrolimus and short-term methotrexate for graft-versus-host
      disease prophylaxis: single-institution analysis.
AB  - We studied clinical outcomes of 25 adult patients with hematological malignancies
      who underwent cord blood transplantation (CBT) after a myeloablative conditioning
      regimen, including high-dose cytosine arabinoside (CA) (8 g/m(2)),
      cyclophosphamide (CY) (120 mg/kg), and total-body irradiation (TBI) (12 Gy). For
      graft-versus-host disease (GVHD) prophylaxis, all patients received a combination
      of tacrolimus and short-term methotrexate (sMTX). Neutrophil engraftment was
      achieved in 20 of 25 patients. Of the 22 evaluable patients, 2 and 7 had grades I
      and II acute GVHD, respectively, and only 1 developed grade III acute GVHD after
      discontinuation of tacrolimus due to encephalopathy. Chronic GVHD developed in 13
      of 19 evaluable patients, including 4 with the extensive type. However, the
      Karnofsky scores of survivors at 1 year after CBT were 90% or 100%. Eight of 25
      patients died of nonrelapse causes (n = 4) and relapse/progressive disease (n =
      4); 17 patients are currently alive with 15 free of disease at the present time
      (median follow-up, 24 months). The probability of disease-free survival at 2
      years among patients with standard risk was 89% and that of high-risk patients
      was 30%. Transplantation-related mortality within 100 days was 12%. These results
      suggested that the CA/CY/TBI combination is a promising conditioning regimen for
      myeloablative CBT. Furthermore, tacrolimus and sMTX seemed to have suppressed
      severe acute GVHD and chronic GVHD, which may also contribute to the favorable
      results.

PMID- 19100457
TI  - Evaluation of readmission in children receiving allogeneic hematopoietic stem
      cell transplantation: an institutional experience.
AB  - BACKGROUND: Use of unrelated cord blood (UCB) has become increasingly popular as
      a stem cell source, given the rapid availability and decreased potential of graft
      versus-host disease. We sought to ascertain whether the use of UCB
      transplantation for pediatric patients changed the rates of unscheduled
      readmission. METHODS: We analyzed the rate, causes, and evolution of
      hospitalization among patients receiving UCB versus matched sibling bone marrow.
      A retrospective analysis of the data from 54 patients who received a matched
      sibling hematopoietic stem cell transplantation (HSCT; n = 25; 46.3%) versus an
      unrelated cord blood transplantation (CBT; n = 29; 53.7%) was performed on
      subjects treated between 1998 and 2006. Patients who died before discharge (n =
      4) were excluded from the readmission analysis. RESULTS: A total of 50 patients
      were recruited for the analyses. Their median age was 6.7 years (range = 0.2-17
      years). The median duration of hospitalization was 18 days shorter in the sibling
      HSCT group than in the unrelated CBT group. There were 89 readmissions in 25
      patients (50%): 49 readmissions (55%) in the related HSCT and 40 (45%) in the
      unrelated CBT cohorts. Forty-two percent of readmissions were due to infections.
      Mortality following transplantation in 10 patients (19%) included sepsis (n = 3),
      intracranial hemorrhage (n = 1), pulmonary hemorrhage (n =1), and relapse (n =
      5). Seven patients received HSCT from HLA-identical sibling donors and three from
      a cord blood donor. CONCLUSION: For both groups, infection was the most common
      reason for readmission followed by graft failure and extramedullary relapse.
      Although the median hospital stay was shorter in the sibling donor group, some
      uncertainty exists as to whether the increased risk for readmission was related
      to proportionally more malignancies or to the severity of the illness. After
      HSCT, there was a frequent use of hospital resources: 46% of patients were
      hospitalized for a median of 11 days. The resulting health expenses seem to be
      useful, since 81% of subjects survived at 36-month follow-up.

PMID- 19100458
TI  - Neural stem cell transplantation rescues rectum function in the aganglionic rat.
AB  - BACKGROUND: Neural stem cell (NSC) transplantation is a promising tool for
      restoring the nervous system in a variety of neurodegenerative disorders. The aim
      of this study was to determine the potential of NSC transplantation as a
      therapeutic strategy for neuronal replacement of the enteric nervous system of
      the rectum in an aganglionic rat. MATERIALS AND METHODS: Rat central nervous
      system-derived NSCs (CNS-NSCs) obtained from the cortex of the fetal brain (E16)
      were transplanted into the benzalkonium chloride (BAC)-induced rat aganglionic
      rectum. Survival and differentiation of the implanted cells were assessed at 8
      weeks posttransplantation using immunostaining and Western blotting. The
      rectoanal inhibitory reflex (RAIR) was also be measured. RESULTS: Eight weeks
      following transplantation, grafted CNS-NSCs differentiated into neurons and glial
      cells in the aganglionic rectum. The protein expression of neuronal nitric oxide
      synthase (nNOS) and choline acetyltransferase (ChAT) were significantly increased
      and the RAIR restored after cell implantation. CONCLUSIONS: CNS-NSC
      transplantation may provide a viable therapeutic option for disorders of the
      enteric nervous system.

PMID- 19100459
TI  - Stromal-derived factor-1 up-regulated the expression of MIC on mouse keratinocyte
      stem cells.
AB  - Although previous studies have demonstrated that stromal-derived factor-1 (SDF-1)
      played a key role in chronic graft dysfunction (CGD), the precise mechanisms
      underlying this process are not clear. In this study, SDF-1 was injected into
      keratinocyte stem cells (KSCs) which were isolated and purified from neonatal
      C57BL/6 (H-2b) mice. Adenylyl cyclase (AC) activity of KSCs was measured and
      expressions of the human major histocompatibility complex (MHC) class I chain
      related antigens A and B (MICA, MICB) detected by immunofluorescence. Cultured
      KSCs were negative for IA/IE MHC class II molecules by immunofluorescence,
      indicating the absence of any contamination with Langerhans cells and certifying
      the purity of KSCs. Over a 7-day culture period, SDF-1 up-regulated AC activity
      to 2.783 +/- 0.799, which was higher than that of the control group (1.290 +/-
      0.476; P < .01). Immunostaining showed that KSCs expressed increased amounts of
      MICA protein (0.790 +/- 0.134 versus 0.200 +/- 0.022; P < .01) and MICB protein
      (0.610 +/- 0.832 versus 0.230 +/- 0.016; P < .01). Mixed lymphocyte reaction
      assays showed that KSCs cultured with SDF-1 injection for 7 days stimulated
      allogeneic T-cell proliferation. The data indicated that SDF-1 may accelerate the
      ultimate rejection of allogeneic keratinocytes by enhancing MIC through the AC
      signal pathway.

PMID- 19100460
TI  - Gene transfer using recombinant simian virus 40 viral vectors into mice bone
      marrow progenitor cells depressed the immunogenicity of keratinocyte stem cells.
AB  - Hematopoietic stem cell (HSC) gene transfer has been attempted almost entirely ex
      vivo and has been limited by loss of self-renewal capacity and transplantation
      related defects in homing and engraftment. Herein we have attempted to overcome
      these limitations by injecting vectors directly into the bone marrow (BM) to
      transduce HSCs in their native environment. Simian virus 40 (SV40)-derived gene
      delivery vectors were used because they efficiently transduce resting CD34+
      cells. Neonatal C57BL/6 (H-2b) mice (3 days old) received SV(Nef-FLAG), carrying
      FLAG marker epitope directly into both femoral marrow cavities. Keratinocyte stem
      cells (KSCs) were purified at 7 and 14 days after SV40 injection. The KSCs from
      10-day-old C57BL/6 mice were designated as controls. Flow cytometric (FCM)
      analyses indicated that KSCs from transgenic mice showed strong down-regulation
      of surface immunological molecules CD40, CD80, CD86, and human major
      histocompatibility complex class I chain-related antigen A (MICA). Mixed
      lymphocyte reaction (MLR) assays showed that transgenic KSCs depressed allogeneic
      T-cell proliferation. Immunofluorescence showed transgenic KSCs expressed FLAG
      for the entire study as well as high levels of transforming growth factor (TGF)
      beta and BCL-2. Thus, direct intramarrow administration of recombinant SV40
      yielded efficient gene transfer to mice BM progenitor cells. KSCs with low
      immunogenicity may be obtained for further investigations of skin transplantation
      immunity.

PMID- 19100461
TI  - Pulmonary aspergillosis in solid organ transplant patients: a report from Iran.
AB  - BACKGROUND: Aspergillosis is one of the most important opportunistic infections
      after organ transplantation. Early diagnosis and initiation of appropriate
      antifungal therapy are key factors for better prognosis. METHODS: We reviewed the
      medical records of patients with solid organ transplantation with evidence of
      Aspergillus infections from December 2001 to January 2008, evaluating patient
      demographics, time of onset after transplantation, risk factors, radiologic
      appearance, diagnostic criteria, antifungal therapy, and outcome. RESULTS: We
      observed aspergillosis in 8 lung, 3 kidney, and 1 heart recipient, with overall
      mean age of 40.6 years. Seven cases of Aspergillus tracheobronchitis were
      diagnosed in lung transplant recipients, all of them in the first 6 months after
      transplantation. All patients responded to antifungal therapy and bronchoscopic
      debridement. We observed 5 cases of invasive pulmonary aspergillosis. Three
      patients survived in response to antifungal treatment. The two patients who died
      were treated with a combination of itraconazole and amphotericin B, whereas all
      cured patients had been treated with voriconazole alone or in combination with
      caspofungin. CONCLUSION: It seems that the prognosis of aspergillosis in solid
      organ recipients is improving with new treatment regimens, particularly if they
      are used in early stages of infection.

PMID- 19100462
TI  - Estimation of abbreviated mycophenolic acid area under the concentration-time
      curve during early posttransplant period by limited sampling strategy.
AB  - Area under the concentration curve (AUC) of mycophenolic acid (MPA) could help to
      optimize therapeutic drug monitoring during the early post-renal transplant
      period. The aim of this study was to develop a limited sampling strategy to
      estimate an abbreviated MPA AUC within the first month after renal
      transplantation. In this study we selected 19 patients in the early
      posttransplant period with normal renal graft function (glomerular filtration
      rate > 70 mL/min). Plasma MPA concentrations were measured using reverse-phase
      high-performance liquid chromatography. MPA AUC(0-12h) was calculated using the
      linear trapezoidal rule. Multiple stepwise regression analysis was used to
      determine the minimal and convenient time points of MPA levels that could be used
      to derive model equations best fitted to MPA AUC(0-12h). The regression equation
      for AUC estimation that gave the best performance was AUC = 14.46 C(10) + 15.547
      (r(2) = .882). The validation of the method was performed using the jackknife
      method. Mean prediction error of this model was not different from zero (P > .05)
      and had a high root mean square prediction error (8.06). In conclusion, this
      limited sampling strategy provided an effective approach for therapeutic drug
      monitoring during the early posttransplant period.

PMID- 19100463
TI  - Is the affinity column-mediated immunoassay method suitable as an alternative to
      the microparticle enzyme immunoassay method as a blood tacrolimus assay?
AB  - BACKGROUND: Tacrolimus is a potent immunosuppressive drug used in organ
      transplantation. Because of its substantial toxic effects, narrow therapeutic
      index, and interindividual pharmacokinetic variability, therapeutic drug
      monitoring of whole-blood tacrolimus concentrations has been recommended. We
      investigated the comparability of the results of 2 immunoassay systems, affinity
      column-mediated immunoassay (ACMIA) and microparticle enzyme immunoassay (MEIA),
      comparing differences in the tacrolimus concentrations measured by the 2 methods
      in relation to the hematologic and biochemical values of hepatic and renal
      functions. METHODS: A total of 154 samples from kidney or liver transplant
      recipients were subjected to Dimension RxL HM with a tacrolimus Flex reagent
      cartilage for the ACMIA method and IMx tacrolimus II for the MEIA method.
      RESULTS: Tacrolimus concentrations measured by the ACMIA method (n = 154) closely
      correlated with those measured by the MEIA method (r = 0.84). The Bland-Altman
      plot using concentration differences between the 2 methods and the average of the
      2 methods showed no specific trends. The tacrolimus levels determined by both the
      MEIA method and the ACMIA method were not influenced by hematocrit levels, but
      the difference between the 2 methods (ACMIA - MEIA) tended to be larger in low
      hematocrit samples (P < .001). CONCLUSION: The ACMIA method used for a tacrolimus
      assay is precise and has advantages, including the lack of a required
      pretreatment procedure. Furthermore, it is only slightly influenced by the
      hematologic or biochemical status of the samples.

PMID- 19100464
TI  - Tripterygium wilfordii hook f increase the blood concentration of tacrolimus.
AB  - OBJECTIVE: To observe the influence of the Tripterygium wilfordii Hook F (T II)
      on the blood concentration of tacrolimus and analyze the impact of this effect.
      METHOD: Twenty-two renal transplant receipts taking tacrolimus combined with the
      T II were selected for this study. We analyzed the blood concentrations and the
      rate of concentration compared with dosage (C/D rate) pre- and postcombination
      over 6 months. All cases underwent the CYP3A5 genotype test. RESULT: The
      concentrations of tacrolimus were raised to a certain degree after the
      combination in all the cases. The first-time elevation differed from 1 week to 4
      months. The C/D rate increased by 1.7 to 7.2 times with most evaluated C/D rates
      ranging from 1.8 to 3.8. The elevated C/D rate of the subgroup of CYP3A5 1/1 and
      1/3 (n = 10) contrasted with the 3/3 genotype subgroup (n = 12: 2.99 +/- 1.71 vs
      2.55 +/- 1.07; P = .472). The mycophenolate mofetil subgroup (n = 17) was not
      contrasted to the mizoribine subgroup (n = 5: 2.85 +/- 1.51 vs 2.31 +/- 0.26; P =
      .498). CONCLUSION: T II considerably increased the blood concentration and the
      C/D rate of tacrolimus. The degree of increase was probably not related to the
      CYP3A5 genotype and the combination of immunosuppressive agents.

PMID- 19100465
TI  - Human herpesvirus-8 serology in pediatric organ transplantation.
AB  - Human herpesvirus (HHV)-8 has been demonstrated to be involved in the
      pathogenesis of Kaposi's sarcoma, body cavity lymphomas, multicentric Castleman
      disease, and, more recently, acute bone marrow failure. In order to study the
      correlation between HHV-8 and immunosuppression, we performed a serological study
      in a group of 28 pediatric heart and heart-lung transplant recipients; of mean
      age 11.5 +/- 2.5 years. We analyzed blood samples prior to, at 3 to 6 months, and
      at least 12 months after transplantation. All patients were negative
      pretransplantation. We observed 10 seroconversions: one patient at 6 months; two
      patients at 12 months; and seven within the third year after transplantation. Our
      preliminary data demonstrated that HHV-8 seroconversion is frequent among
      pediatric transplant recipients. It was probably related to the length of
      immunosuppression rather than the organ transplantation; Serological assays of
      all donor specimens of seroconverted patients were negative.

PMID- 19100466
TI  - High prevalence of microchimerism in female patients.
AB  - Evaluation of free plasma DNA has been suggested as one of the option to detect
      organ rejection in transplanted patients. However, the presence of chimeric cells
      in organs could make this approach complicated. To study the presence of Y
      chromosome chimeric cells, we examined biopsy samples of 40 thoracic aortas of
      female donors and recipients. Using nested polymerase chain reaction, the
      presence of Y-chromosome-specific DNA sequences was detected in 19 (47.5%)
      analyzed tissue samples. Thus, free DNA originating from more than two genomes
      could be present in plasma in such a high proportion of cases. This phenomenon
      makes the use of plasma free DNA for the detection of organ rejection difficult
      and impractical.

PMID- 19100467
TI  - Temporal profile of calcineurin phosphatase activity during acute allograft
      rejection in the heterotopic rat heart transplantation model.
AB  - BACKGROUND: Regardless of the extensive worldwide use of calcineurin inhibitors,
      little is known about the behavior of calcineurin phosphatase (CaN) during acute
      allograft rejection. The aim of this study was to investigate the temporal
      profile of CaN during acute allograft rejection and reveal if it can be utilized
      as a pharmacodynamic marker to identify and monitor the rejection process.
      METHODS: The heterotopic cervical rat heart transplantation model was used (dark
      Agouti to Lewis). We performed 25 control isogeneic and 46 allogeneic
      transplantations. Rats were sacrificed at various postoperative time points. CaN
      activity was measured in isolated peripheral blood and spleen mononuclear cells
      and in graft heart homogenates. CaN activity was measured as the release of
      radiolabeled phosphate from a previously phosphorylated 19 amino acid peptide.
      RESULTS: We have shown that CaN's activity levels are not significantly altered
      during acute allograft rejection in peripheral blood mononuclear cells and in
      spleen-isolated mononuclear cells. CaN's intragraft activity decreased with time
      in both rejectors and controls, and was significantly lower in the allogeneic
      group. CONCLUSIONS: CaN failed as a pharmacodynamic biomarker of acute allograft
      rejection in the heterotopic rat heart transplantation model. Further research is
      required in order to reveal the precise role of CaN during acute allograft
      rejection.

PMID- 19100468
TI  - A combination of donor specific transfusion and rapamycin prolongs cardiac
      allograft survival in mice.
AB  - BACKGROUND: We sought to investigate the effects of donor-specific transfusion
      (DST) combined with rapamycin (RPM) on engraftment and demonstrate the
      mechanisms. METHODS: B6 was treated with DST (on day -8) combined with RPM (from
      day -7 to -1, 1.5 microL/g per day). On day 0, B6 splenocytes were harvested to
      coculture with Balb/c splenocytes pretreated with mitomycin C in 1-way mixed
      lymphocyte cultures (MLC). After 48 hours, the proliferation, we measured
      apoptosis and the CD4(+)CD25(+) T-cell ratio of cultured cells. The heterotopic
      cardiac transplantation model was performed from Balb/c to B6 using the
      recipients pretreated with this protocol. On day 0, RPM was withdrawn and the
      transplantations performed. The mean survival time (MST) of the grafts evaluated
      and in vitro assays measured. RESULTS: Both in vitro and in vivo, the protocol
      suppressed the proliferation of splenocytes as well as enhanced apoptosis and the
      CD4(+)CD25(+) T-cell ratio. The MST of the grafts was 35 +/- 14.4 days.
      CONCLUSIONS: Our study showed that DST combined with RPM prolonged cardiac
      allograft survival even if we withdrew immunosuppressants after transplantation.
      This result may be associated with inhibition of T-cell proliferation. We also
      demonstrated that RPM expanded CD4(+)CD25(+) T cells and increased splenocyte
      apoptosis.

PMID- 19100469
TI  - Vascular endothelial dysfunction in cyclosporine-treated rat aortas is not
      associated with serum total homocysteine levels.
AB  - OBJECTIVES: Elevation of serum total homocysteine (tHcy) is considered to
      contribute to endothelial cell dysfunction, which is considered to be the initial
      event in posttransplant vascular disease. We sought to investigate whether an
      association existed between serum tHcy levels and vascular endothelial function
      during cyclosporine (CsA) treatment. MATERIALS AND METHODS: Endothelium-dependent
      and -independent relaxation responses (to acetylcholine [ACh] and sodium
      nitroprusside [SNP]) were determined on thoracic aortae from CsA-treated rats (5
      mg kg/d, subcutaneously, for 14 days). A correlation analysis was performed
      between ACh responses and tHcy levels. RESULTS: CsA decreased the responses to
      ACh and the pD(2) values of the concentration-response curves compared with
      controls (P < .05). Responses to SNP and serum tHcy levels were unchanged among
      the groups. tHcy negatively correlated with the ACh pD(2) values among control (r
      = -0.69; P < .05) and vehicle (r = -0.73; P < .05) groups, indicating that the
      increase in tHcy was associated with decreased sensitivity to ACh. In CsA-treated
      rats, no association was observed between these parameters. Also, no correlation
      was noted between CsA concentrations and tHcy levels. CONCLUSION: These data
      suggested a possible link between serum tHcy and decreased vascular sensitivity
      to endothelium-dependent vasorelaxation in control aortae, but CsA-induced
      vascular endothelial dysfunction was not associated with an effect of the drug on
      homocysteine metabolism.

PMID- 19100470
TI  - Donor bone-marrow suppressor of cytokine signaling-1-silenced dendritic cells
      prolong rat intestinal allograft survival.
AB  - Suppressor of cytokine signaling (SOCS) molecules belong to intracellular
      proteins that inhibit Janus kinase as well as signal transduction and activators
      of transcription pathways. In this study, we investigated whether SOCS-1-silenced
      dendritic cells (DCs) prolonged allograft survival in rat intestinal
      transplantation. Donor bone marrow-derived DCs were genetically transfected with
      SOCS-1 siRNA using liposomes. The level of SOCS-1 expression was quantitated by
      Western blots. DC function was assessed by MTT in mixed leukocyte reactions. We
      injected donor-derived SOCS-1 silenced DCs 7 days before heterotopic intestinal
      transplantation between SD donors and Wistar recipients. We compared
      untransfected DCs and silenced DCs to suppress allogeneic mixed leukocyte
      reactions. Recipients pretreated with SOCS-1-silenced DCs showed moderate
      survival prolongation with a mean allograft survival of 18.3 +/- 5.3 days (P <
      .05), compared with 6.4 +/- 2.0 days in the control group and 7.2 +/- 2.1 days in
      a control siRNA transfection DC group. The difference between untreated DCs group
      and the control group was not significant. In summary, SOCS-1 silenced DCs
      induced allogeneic T-cell hyporesponsiveness in vitro, promoting allograft
      survival in rat intestinal transplantation.

PMID- 19100471
TI  - Prolongation of rat intestinal allograft survival by administration of triptolide
      modified donor bone marrow-derived dendritic cells.
AB  - Severe graft rejection remains an important obstacle in intestinal
      transplantation. In this study, dendritic cells (DCs) isolated from rat bone
      marrow were cultured for 5 days, and triptolide applied for 3 more days. The
      recipient rats were pretreated with donor triptolide-modified or not modified DC.
      Small bowel transplantation was performed to observed survival times. We
      demonstrated that triptolide markedly inhibited both the expression of CD80 and
      MHCII expression on DCs. Triptolide-modified DCs stimulated lower proliferative
      responses among allogeneic T cells, prolonging the survival of intestinal
      allografts in rats. These results suggested that pretreatment with triptolide
      modified DC prolonged the survival of rat small bowel allografts after
      transplantation.

PMID- 19100472
TI  - Trichosanthin, an extract of Trichosanthes kirilowii, effectively prevents acute
      rejection of major histocompatibility complex-mismatched mouse skin allograft.
AB  - Trichosanthin is an active component extracted from the root tuber of the Chinese
      medicinal herb Trichosanthes kirilowii. Trichosanthin has abortifacient, anti
      tumor, anti-HIV, and immunoregulatory functions. In the current study, we
      explored its potential effect on allograft rejection in a murine skin
      transplantation model across a fully mismatched major histocompatibility complex.
      It was found that treatment of recipient mice with trichosanthin (0.25 or 1
      mg/kg, IP) significantly delayed allograft rejection. T cells that originated
      from recipients treated with trichosanthin were restimulated with donor-specific
      splenocytes showed a significantly reduced response compared with that of control
      recipients. In line with these results, the mRNA levels for interleukin (IL)-2
      and interferon-gamma were decreased and the levels of IL-4 and IL-10 were
      increased in splenic T cells originating from trichosanthin-treated recipients.
      These results indicated that trichosanthin may have potential therapeutic value
      for transplantation rejection and other inflammatory diseases.

PMID- 19100473
TI  - Protosappanin a, an immunosuppressive constituent from a Chinese herb, prolongs
      graft survival and attenuates acute rejection in rat heart allografts.
AB  - OBJECTIVE: Caesalpinia sappan L., which has been used in oriental medicine as an
      analgesic and antiinflammatory agent, has shown immunosuppressive activity on
      acute rejection on rat heart allografts. The present study was designed to
      investigate the potency of protosappanin A, one major ingredient of C. sappan L.,
      in rat heart transplantation. MATERIALS AND METHODS: Protosappanin A isolated
      from an ethanol extract of C. sappan L. was identified by wave spectrum. All
      groups consisted of Wistar donors into Sprague-Dawley (SD) recipients, including
      large (25 mg/kg) or small (5 mg/kg) doses of protosappanin A plus cyclosporine
      (10 mg/kg). A control group was used. Animals were given the drugs on
      postoperative day 2. We observed graft survival and pathologic conditions of the
      hearts. Blood samples were obtained on postoperative day 7 to measure the
      CD4+/CD8+ T-cell ratio. Graft perforin and granzyme B mRNA expression levels were
      examined with reverse transcription-polymerase chain reaction (RT-PCR) methods.
      RESULTS: Protosappanin A or cyclosporine significantly prolonged heart allograft
      survival (P < .01), alleviated myocardial pathologic damages (P < .01), decreased
      the CD4+/CD8+ ratio (P < .05), and inhibited perforin and granzyme B mRNA
      expressions in the graft (P < .05). CONCLUSIONS: These findings demonstrated that
      protosappanin A prolonged heart allograft survival by significantly attenuating
      acute rejection.

PMID- 19100474
TI  - Costimulation blockade of CD40 and CD28 pathways in limb transplantation.
AB  - Costimulation blockade remains a promising experimental regimen for the induction
      of transplantation tolerance. The simultaneous blockade of both the CD40 and CD28
      pathways has been synergistic in prolonging organ allograft survival but has not
      previously been investigated in a model of limb allotransplantation. This study
      determined the efficacy of this combination in the murine limb allograft model.
      C57B1/6 (H-2K(b)) female mice were recipients of heterotopic vascularized limb
      allografts from Balb/c (H-2K(d)) male donors. Experimental groups received
      treatment with a short course of MR1 (hamster anti-mouse anti-CD40 ligand
      antibody) alone or in combination with CTLA4-Ig, a fusion protein that blocks the
      B7/CD28 pathway. Untreated recipients rejected limb allografts at a mean of 9.6
      +/- 1.1 (standard error of the mean) days postoperatively. Recipients of a
      prolonged course of MR1 rejected limb allografts at 75 +/- 25 days. When both MR1
      and CTLA4-Ig were used, limb allograft survival of >120 days was observed despite
      a much shorter course of therapy. Rejection in both treatment groups was
      consistent with a chronic antibody-mediated process. Donor antigen rechallenge in
      these recipients by in vitro assay and skin allograft demonstrated a hyperacute
      response consistent with presensitization. Long-term limb allograft survival is
      produced by the synergistic effect of blocking both the CD40 and CD28
      costimulatory pathways. However, permanent acceptance was not achieved, and
      allografts eventually succumbed to what appeared to be antibody-mediated
      rejection. The additional use of newer agents that block more recently described
      costimulatory pathways may be essential for the induction of tolerance by
      costimulation blockade.

PMID- 19100475
TI  - Prolonged survival of renal allograft in rats by methotrexate-albumin conjugates
      as immunosuppressive therapy.
AB  - Methothrexate (MTX) causes unwanted adverse events by affecting gastrointestinal
      and bone marrow cells when used as an immunosuppressant. Our aim was to reduce
      those side effects by covalent binding of methothrexate to human serum albumin
      (HSA) targeting rapidly proliferating lymphocytes, which are known to ingest
      albumin as an energy source. Twenty-one rats received a kidney transplant. Group
      A (n = 5) received standard immunosupression (free MTX); group B (n = 9), albumin
      MTX conjugates; and group C (n = 7) albumin control. The primary endpoint of this
      animal study was transplant survival, which was evaluated as death due to uremia.
      The study was terminated on day 100. Placebo-treated rat recipients (group C)
      rejected their grafts at a median of 8 days, which was prolonged to 17 days in
      standard immunosuppressed rats (group A), resulting in doubling transplant
      survival compared to nonimmunosuppressed animals. However, the same dose given as
      HSA-conjugated MTX prolonged the median survival time to 43 days. (group B).
      Hence, the administration of conjugated methotrexate appeared to result in a
      doubling of transplant survival compared with standard immunosuppression.
      Moreover, two animals receiving MTX-HSA became long-term survivors without
      additional immunosuppression. Further studies should be performed to evaluate the
      significance of these findings in larger animals and possibly in clinical
      studies.

PMID- 19100476
TI  - Transplantation of both kidneys from one donor rat using end-to-end vascular
      anastomosis in normal saline.
AB  - BACKGROUND: End-to-end vascular anastomosis in the 0.9% NaCl solution was
      compared with conventional end-to-end vascular anastomosis in the model rat, with
      two kidneys from one donor rat harvested and transplanted to two recipient rats.
      METHODS: Two methods of suturing renal walls were used. In group A, the
      conventional end-to-end anastomosis was performed, where one person stitched
      veinous walls while the other washed them using the normal saline (n = 20). In
      group B, end-to-end anastomosis of renal vein walls was performed in 0.9% NaCl
      solution (n = 20). RESULTS: In the normal saline, the renal vein walls naturally
      extended and separated and the edges of the renal veins were revealed. In group
      B, the operation time and overall complication rate of suturing were reduced (P <
      .001). CONCLUSION: This is the first report of end-to-end vascular anastomosis in
      the normal saline in the model of rat kidney transplantation. This method, which
      does not require any special instruments, is fast, safe, and needs only one
      surgeon to perform the renal vascular suturing, and may be applied to other
      transplantation models.

PMID- 19100477
TI  - Treatment of chronic allograft nephropathy at late stages using everolimus or
      FTY720 in combination with cyclosporine.
AB  - OBJECTIVE: In this study, we used combined treatment with cyclosporine
      (CsA)/everolimus (EVR) or CsA/FTY720 to affect ongoing chronic allograft
      nephropathy (CAN) compared with monotherapy with EVR or FTY720. BACKGROUND: CAN
      is an important cause of renal allograft loss. Immunosuppressive therapy is based
      on calcineurin inhibitors, which are associated with nephrotoxicity and
      decreasing graft function. Thus, alternative treatment regimens, including new
      immunosuppressants, such as EVR or FTY720, are of interest. We asked whether the
      combination of CsA with EVR or FTY720 ameliorated the development of CAN more
      effectively than monotherapy with EVR and/or FTY720 during the later stages of
      CAN. METHODS: Kidneys from Fisher rats were orthotopically transplanted into
      Lewis rats. Animals received CsA (1.5 mg/kg/d) for the first 10 days after
      transplantation. Animals were assigned to 6 groups: EVR (0.5 mg/kg/d), FTY720
      (0.5 mg/kg/d), CsA (1.5 mg/kg/d), CsA+EVR (1.5 + 0.5 mg/kg/d), CsA+FTY720 (1.5 +
      0.5 mg/kg/d), and vehicle (VEH). Treatment started at week 20. The observation
      period ended after 28 weeks. RESULTS: Treatment with EVR and FTY720 reduced
      proteinuria and glomerulosclerosis, suppressed lymphocyte and macrophage
      infiltration, and resulted in a greater number of apoptotic tubular and
      interstitial cells compared with the combined treatment groups and controls.
      CONCLUSION: Although EVR and FTY720 monotherapy delayed the progression of CAN,
      their combination with CsA had no beneficial effect.

PMID- 19100478
TI  - Effect of isoproterenol on cyclosporine-induced nephrotoxicity in rat.
AB  - BACKGROUND: Oxidative stress is the main mechanism resulting in cyclosporine
      induced nephrotoxicity. Because of its ability to stimulate endogenous melatonin
      production, isoproterenol is one of the most powerful antioxidant drugs. In this
      study, we sought to determine the effect of isoproterenol on cyclosporine-induced
      nephrotoxicity in rats. MATERIALS AND METHODS: Thirty two young male Wistar rats
      were divided into four groups: of group A were controls that received placebo;
      group B, received intraperitoneal isoproterenol (20 mg/kg/d) alone; group C,
      intravenous cyclosporine (15 mg/kg/d) alone; and group D, both drugs
      simultaneously at the same doses and durations namely cyclosporine 1 week after
      administration of isoproterenol. Blood samples to measure serum urea, creatinine,
      and melatonin levels were drawn four times for each group: before injection, at
      the mid period of treatment, at the end of treatment, and 1 week after the last
      injections. RESULTS: Isoproterenol increased mean serum melatonin level in groups
      B and D rats (P < .05). With regard to deteriorated renal function [DRF = (urea +
      creatinine)/2], administration of cyclosporine with (group D) or without (group
      C) isoproterenol was associated with decreased renal function (P < .05), although
      it was more perturbed in the latter instance. Measured DRF at the middle and the
      end of drug administration periods of A and B (revealed significant differences
      compared with groups C and D; P < .05). DISCUSSION: Although cyclosporine-induced
      nephrotoxicity is not completely eliminated by isoproterenol, the latter showed
      some protective effects.

PMID- 19100479
TI  - Transmissible infection of human 293T cells with porcine endogenous retroviruses
      subgroup a from NIH-miniature pig.
AB  - In pig-to-human xenotransplantation, zoonotic infections have been an important
      barrier. The risk of zoonosis has been emphasized in xenotransplantation after
      finding that porcine endogenous retroviruses (PERVs) can infect human cells in
      vitro. Until now, transmissions of PERVs from PK15 cells have been studied in
      vitro and in vivo, but transmission of PERVs originating from miniature pigs have
      not been extensively reported. Peripheral blood mononuclear cells from miniature
      swine showed PERV transmission to human cells. In contrast, specific pathogen
      free (SPF) pig islet cells showed no PERV transmission when co-incubated with
      293T cells. To evaluate the risk of zoonosis with our experimental mini pigs, we
      tested the infectivity of PERVs from NIH-miniature pig primary ear cells for
      human 293T cells. As a result, all subgroups of infectious PERV virion (PERV-A, 
      B, and -C) were detected in the primary cell culture media. Unlike PERV-C, PERV-A
      and -B infected human 293T cells. Interestingly, only proviral PERV-A replicated
      in 293T cells to produce virions after infection. Our results suggested that a
      prevention study of PERV xenotransmission from experimental miniature pigs should
      concentrate on PERV-A control.

PMID- 19100480
TI  - Bacteriocins from lactic acid bacteria increases tumor necrosis factor-alpha
      expression in a rat kidney model of chronic rejection.
AB  - Chronic allograft dysfunction is the primary cause of graft loss after the first
      posttransplantation year. Bacteriocins are biologically active proteins
      exhibiting antimicrobial properties against other bacterial species, which are
      usually closely related to the producer organism. The objective of our study was
      to determine whether lactic acid bacterial bacteriocins were associated with
      tumor necrosis factor (TNF)-alpha observed in a rat kidney model of chronic
      rejection. Using a kidney model of chronic rejection in the rat, we administered
      cyclosporine (CsA) immunosuppression (5 mg/kg/d). One group of animals was
      treated with bacteriocins, and the other was left untreated. Grafts were
      harvested after transplantation for standard histological studies. The expression
      of TNF-alpha was demonstrated using immunohistochemistry of frozen sections of
      the grafts. We observed a greater increase in the expression of TNF-alpha among
      the group treated with bacteriocins compared with the untreated group. These
      results showed that lactic acid bacterial bacteriocins were associated with TNF
      alpha in our kidney graft model.

PMID- 19100481
TI  - Incidence and clinical behavior of papillary thyroid carcinoma in renal allograft
      recipients: a single center experience.
AB  - The chronic use of immunosuppressive therapy in transplant recipients increases
      the long-term risk for carcinoma. However, there is insufficient knowledge
      regarding the incidence and biological behavior of papillary thyroid carcinomas
      (PTC) in renal allograft recipients. In the present study we examined the
      incidence and biological behavior of PTCs among 1739 patients transplanted
      between January 1986 and December 1999 who had been followed for a mean period of
      137 months (range, 84-238 months). During the follow-up, 129 (7.4%) recipients
      were identified to display posttransplantation malignancies, including 12 (0.7%)
      with PTCs. The 6 male and 6 female patients had a mean age of 41 years (range, 23
      57 years). Nine cases (incidentalomas) were diagnosed based on ultrasonographic
      (US) screening. Eight of those 9 were TNM stage I, 2 of the 3 clinical carcinomas
      were TNM stage IVa. During a mean follow-up of 94 months (range, 18-159 months),
      2 (16.7%) PTC patients developed locoregional recurrence, but no patients showed
      distant metastases. These data showed that recipients had a higher incidence of
      PTC compared with the general Korean population (0.7% vs 0.02%).
      Posttransplantation PTC tended to show no difference in gender distribution, and
      was often associated with aggressive lymphatic metastasis. However, most
      incidentalomas showed favorable treatment outcomes. In conclusion, routine
      surveillance of the thyroid gland using US screening is recommended to ensure
      early detection, treatment, and favorable prognosis of PTC.

PMID- 19100482
TI  - Central retinal vein thrombosis and hyperhomocysteinemia in a young patient with
      renal transplantation.
AB  - A 28-year-old woman was admitted with a sudden loss of vision in the right eye.
      She underwent renal transplantation in June 1999 for chronic renal failure
      secondary to amyloidosis. Upon ophthalmologic examination, the patient was
      diagnosed with central retinal vein occlusion. Physical and laboratory
      examinations failed to disclose any remarkable pathology except for high
      homocysteine levels. Hyperhomocysteinemia has been reported as a potential risk
      factor requiring treatment and a significant association has been found between
      this condition and central retinal vein thrombosis.

PMID- 19100483
TI  - A Salmonella infection complicated with suppurative thyroiditis and ruptured
      aortic mycotic aneurysm in a renal transplant recipient.
AB  - We report a renal transplant recipient who presented with fever and chills for 2
      days. The blood and stool cultures revealed the growth of Salmonella enteriditis.
      A whole-body gallium scan played an important role in the subsequent diagnosis of
      suppurative thyroiditis. To our knowledge, this is the first report of acute S.
      enteriditis thyroiditis in a renal transplant recipient. Despite vigorous
      antibiotic use and a partial thyroidectomy, he experienced recurrent S.
      enteriditis infection, resulting in a ruptured thoracic mycotic aneurysm 1 month
      later. Finally the patient was successfully cured with aneurysm resection, in
      situ reconstruction of the thoracic aorta, and prolonged antibiotics.

PMID- 19100484
TI  - Successful renal transplantation in a patient with antineutrophil cytoplasmic
      autoantibody-associated microscopic polyangiitis: effect of early plasma exchange
      and mycophenolate mofetil.
AB  - Antineutrophil cytoplasmic autoantibody (ANCA)-associated systemic vasculitis
      readily relapses after renal transplantation; the recurrence often causes graft
      losts. We have reported herein a 53-year-old cadaveric renal allograft recipient.
      His original disease was ANCA-associated microscopic polyangiitis (MPA), which
      was proven by renal biopsy. On postoperative day 4, the patient developed
      dyspnea, hemoptysis, and gross hematuria; the serum p-ANCA titer increased from
      1:40 to 1:80. The patient was immediately treated with 5 sessions of plasma
      exchange. Five days later, the hemoptysis and gross hematuria both disappeared.
      Serum p-ANCA titer recovered to 1:40. The patient showed stable graft function
      for 2 months, until mycophenolate mofetil (MMF) was converted to mizoribine (150
      mg/d). Seven days after the conversion, the serum creatinine increased from 1.27
      to 1.7 mg/dL. Serum p-ANCA increased to 1:160. When mizoribine was converted to
      MMF, 2 days later the renal function and p-ANCA titer recovered. This case report
      suggested that early use of plasma exchange combined with MMF was effective to
      prevent the relapse of ANCA-associated systemic vasculitis after transplantation,
      and may be helpful to improve transplant outcomes.

PMID- 19100485
TI  - Embolization of postbiopsy and postnephrostomy complications in transplanted
      kidney: a case report.
AB  - Complications such as arteriovenous, arteriocalyceal fistula, pseudoaneurysm, or
      perinephric hematoma occur in allografted and native kidneys after interventional
      procedures. When these complications are not detected and treated immediately,
      they might be associated with a poor allograft prognosis. Reoperation may produce
      parenchymal injuries, therefore, endovascular embolization may be a preferred
      treatment modality. Herein we report an arteriocalyceal fistula and an
      arteriovenous fistula in a transplant kidney that were detected after biopsy and
      nephrostomy, respectively, they were treated with endovascular coil embolization.
      Percutaneous treatment is a safe and effective method for arteriocalyceal fistula
      and arteriovenous fistula following interventional procedures in renal
      allografts.

PMID- 19100486
TI  - Non-life-threatening leukopenia in a renal transplant recipient with acute
      overdose of mycophenolate mofetil.
AB  - Mycophenolate mofetil (MMF) is increasingly used as an immunosuppressant for
      organ transplantation and for treatment of autoimmune diseases. As yet, the
      experience with acute overdose of MMF in humans is limited. Herein we have
      reported a 40-year-old female kidney recipient with moderate leukopenia and lack
      of gastrointestinal toxicity following ingestion of 25 g MMF, which was confirmed
      by serum drug levels. We treated the patient with charcoal decontamination and
      oral cholestyramine. She recovered completely without sequelae.

PMID- 19100487
TI  - Effects and problems of adult ABO-incompatible living donor liver transplantation
      using protocol of plasma exchange, intra-arterial infusion therapy, and anti-CD20
      monoclonal antibody without splenectomy: case reports of initial experiences and
      results in Korea.
AB  - INTRODUCTION: Adult ABO-incompatible liver transplantation is associated with a
      high risk of graft failure due to antibody-mediated humoral rejection (AMR). We
      evaluated the effects of a protocol using preoperative removal of
      isohemagglutinin, rituximab prophylaxis, and intrahepatic arterial infusion (HAI)
      therapy for ABO-incompatible adult living donor liver transplantation (LDLT).
      PATIENTS AND METHODS: Between March 2005 and September 2007, we performed 94
      adult LDLTs, including 3 ABO-incompatible cases. All ABO-incompatible LDLT
      patients underwent administration of 375 mg/m(2) rituximab on preoperative days
      15 and 8 without splenectomy, as well as preoperative removal of isohemagglutinin
      using plasma exchange, and HAI therapy for postoperative 21 days. RESULTS:
      Postoperative anti-donor blood-type antibody titer and B-cell level were
      effectively suppressed by early rituximab prophylaxis in all patients. HAI
      therapy was effective to prevent AMR and even resolved mild AMR. However, all
      patients suffered bacterial infections, and 1 died of septicemia with good graft
      function. Another subject died of late-onset AMR that occurred after
      discontinuation of HAI therapy. CONCLUSION: An ABO-incompatible LDLT protocol
      using plasma exchange, rituximab prophylaxis, and intra-HAI therapy effectively
      suppressed anti-A/B antibody and prevented AMR. But this protocol should be
      further improved to reduce infectious complications and late onset of AMR.

PMID- 19100488
TI  - Migration of transjugular intrahepatic portosystemic shunt to the right atrium:
      complications in the intraoperative period of liver transplantation.
AB  - This article reports the case of a patient who underwent transjugular
      intrahepatic portosystemic shunt, which migrated to the right atrium. During
      liver transplantation, the extracardiac portion was sectioned and the portion
      adherent inside the atrium was managed expectantly.

PMID- 19100489
TI  - Extragastrointestinal stromal tumor and liver transplantation: case report and
      review.
AB  - The occurrence of de novo malignant neoplasias has been shown in postransplant
      patients under imunosuppression. It is the second leading cause of late death in
      liver transplant recipients. The greatest incidence is seen in cancers associated
      with chronic infection by human papilloma virus, skin cancers, oropharyngeal, and
      gastrointestinal (GI) malignancies. GI stromal tumors (GISTs) are the most common
      mesenchymal tumors of the GI tract. Rare cases are identified outside the GI
      tract are collectively known as extragastrointestinal stromal tumors (EGISTs). We
      present an EGIST case in a liver transplantation patient. A 64-year-old man
      underwent liver transplantation because of cirrhosis (hepatitis B virus and
      alcoholism) and hepatocellular carcinoma. Histopathologic findings revealed 2
      trabecular hepatocellular carcinomas: a 3.5-cm-diameter lesion located at segment
      VIII and another 2-cm one at segment V. Seven months later, he noticed a
      hardened, mobile, painless, 3-cm subcutaneous nodule in the perineum localized in
      the right lateral quadrant 2 cm distant from the anus. A surgical resection with
      1 cm margin yielded a histopathology report of a 5.0 x 3.0 cm spindle cell
      stromal tumor. The immunohistochemical profile was compatible with a GIST, with 5
      mitosis per 50 high-powered fields. This tumor is extremely rare after liver
      transplantation but has shown a good outcome up to now.

PMID- 19100490
TI  - Graft-versus-host disease after liver transplantation: successful treatment of a
      case.
AB  - Graft-versus-host disease (GVHD) is a rare, serious complication after liver
      transplantation. The incidence is about 1% abroad, but because of difficulties in
      diagnosis and treatment, the mortality rate is high (80%). Up to now, 78 patients
      have been reported to have this complication after liver transplantation
      worldwide; despite various therapeutic programs, the mortality of GVHD after
      orthotopic liver transplantation (OLT) is still high. Herein we have reported
      successful treatment of a case of GVHD after liver transplantation.

PMID- 19100491
TI  - Living donor liver transplantation for unresectable liver metastases from solid
      pseudo-papillary tumor of the pancreas: a case report.
AB  - Solid pseudo-papillary tumors (SPT) are rare primary tumors of the pancreas that
      primarily affect young women. They are of borderline malignancy, and, unlike
      other pancreatic malignancies, the prognosis after resection is quite good.
      However, metastatic disease does occur; the liver is the most common site of
      tumor dissemination. Herein we have reported a case of a 20-year-old woman who
      presented with multiple, bilateral liver metastases at 3 years after distal
      pancreatectomy for SPT of the body and tail of the pancreas. The patient
      underwent living donor liver transplantation (LDLT) and is alive and disease-free
      at 24 months after surgery. In this report, we discuss the treatment of liver
      metastases from SPT, with an emphasis on the possible role of orthotopic liver
      transplantation (OLT).

PMID- 19100492
TI  - Fatal hemophagocytic syndrome related to human herpesvirus-6 reinfection
      following liver transplantation: a case report.
AB  - Human herpesvirus-6 (HHV-6) has been identified as the causal agent of exanthema
      subitum in early childhood (also called sixth disease or roseola), a
      mononucleosis-like disease in adults, and as an opportunistic pathogen in
      transplant recipients. In the latter setting, most infections are caused by
      reactivation of the latent virus in the recipient and generally have a
      paucisymptomatic course. Only limited data on HHV-6 infection are available for
      liver transplant recipients. Herein we have reported a case of fatal
      hemophagocytic syndrome related to HHV-6 reactivation 2 weeks after liver
      transplantation (LT). This case suggests that this virus may be a serious and
      potentially life-threatening pathogen following LT.

PMID- 19100493
TI  - Arterial reconstruction in a case of subintimal dissection of celiac arterial
      tributaries in living donor liver transplantation: a case report.
AB  - BACKGROUND: Hepatic arterial reconstruction is one of the critical issues in
      living donor liver transplantation (LDLT). Herein we have reported an LDLT case
      whose celiac arterial trunk tributaries were insufficient as host arteries
      because of extensive subintimal dissection proceeding to all tributaries of the
      celiac arterial trunk. PATIENTS AND METHODS: A 45-year-old woman with fulminant
      hepatic failure underwent LDLT. After reperfusion of the hepatic and portal
      veins, subintimal dissection of the recipient right and left hepatic arteries was
      found to extend to all tributaries of the celiac arterial trunk, preventing an
      anastomosis using the more proximal part of these arteries. Therefore, a jejunal
      arterial arcade of Roux-en-Y limb mobilized for biliary reconstruction was
      anastomosed to the donor left hepatic artery in end-to-end fashion. RESULTS:
      Arterial blood flow to the grafted liver was established successfully, and the
      patient's postoperative recovery was excellent. Postoperative computed tomography
      demonstrated sufficient hepatic arterial blood flow. The patient is doing well 4
      years after transplantation. CONCLUSION: The method of hepatic graft
      arterialization described herein is an important option for LDLT recipients when
      tributaries of the celiac arterial trunk are insufficient as host arteries.

PMID- 19100494
TI  - Liver transplantation with reconstruction of the inferior vena cava for
      hepatocarcinoma on chronic Budd-Chiari: a case report.
AB  - Management of Budd-Chiari syndrome, from simple medical treatment to liver
      transplantation, depends on the acute and chronic evolution of the disease and on
      the degree of hepatic insufficiency. Herein we have reported the case of a man
      who underwent transplantation after evolution of a Budd-Chiari syndrome with
      membranous obstruction of the vena cava and developed 2 lesions of hepatocellular
      carcinoma. Surgery was difficult due to previous procedures requiring
      reconstruction of the supra-hepatic vena cava. This case emphasized the timing of
      liver transplantation versus other treatments to decrease the operative risk.

PMID- 19100495
TI  - Graft vessel wall pathology in a case of hepatic artery pseudo-aneurysm in a
      liver transplant recipient.
AB  - Pseudo-aneurysms (PAs) of the hepatic artery are rare complications of liver
      transplantation, which are characterized by a high mortality rate. The majority
      occur within the first 2 months after orthotopic liver transplantation. They
      become clinically manifest with sudden hypotension, gastrointestinal bleeding,
      and abnormal liver function test results. Early diagnosis and treatment are
      essential to prevent life-threatening hemorrhage. Conventional treatment consists
      of surgical resection and vascular reconstruction, but a feasible treatment
      option involves an angiographic approach with the positioning of a stent or
      transarterial coil embolization followed by revascularization. We report a case
      of posttransplantation hepatic artery PA (HA-PA) with bleeding into the duodenum,
      diagnosed using abdominal computed tomography (CT). Arterial kinking prevented a
      covered stent graft from being inserted successfully using X-ray angiography, so
      the patient underwent emergency surgery in an attempt to exclude the PA and
      revascularize the organ via an aorto-hepatic bypass with an iliac vascular graft
      obtained from the donor. The surgical procedure failed due to progressive
      macroscopic dissection of the HA wall up to the bifurcation. The patient
      underwent retransplantation but died 25 days later due to multiple-organ failure.
      Histopathology of the first liver graft confirmed arterial graft dissection and
      pathological changes in the donor HA wall.

PMID- 19100496
TI  - Liver transplantation for hepatocellular carcinoma after yttrium therapy: a case
      report.
AB  - Yttrium-90 microspheres constitute one of the most recent treatment options for
      hepatocellular carcinoma (HCC) in the setting of cirrhosis. As such, their
      spectrum of indication is not yet fully established. Herein, we have reported the
      case of a patient with HCC beyond the listing criteria for liver transplantation
      (OLT) who was treated preoperatively with selective transarterial
      chemoembolization and yttrium-90 microspheres. He was subsequently transplanted
      with a liver from an 81-year-old donor allocated through Eurotransplant as a
      "rescue offer." The posttransplant course was uneventful. Pathologic examination
      revealed a multifocal, well-differentiated pT2 tumor with no vascular invasion.
      The patient is currently alive and in good condition at 14 months posttransplant,
      with no evidence of tumor recurrence by a current computed tomography scan. This
      report provided encouraging information on the potential of yttrium-90
      microspheres as a bridging option before OLT for multifocal HCC.

PMID- 19100497
TI  - "Preemptive" live donor liver transplantation for fibrolamellar hepatocellular
      carcinoma: a case report.
AB  - Fibrolamellar (FL) hepatocellular carcinoma (HCC) is a distinctive form of
      primary HCC that occurs principally in children and young adults. Although liver
      transplantation is not contraindicated for FL-HCC, noncirrhotic patients with
      large HCC tumors (including FL-HCCs) are not prioritized. Although hepatic
      resection is considered to be the primary treatment for FL-HCC, living donor
      liver transplantation is evolving into a potentially better alternative. Herein
      we have reported successful "preemptive" living donor liver transplantation for
      presumed recurrence of FL-HCC after an extended right hepatectomy with resection
      and synthetic graft replacement of the inferior vena cava.

PMID- 19100498
TI  - Auxiliary partial orthotopic living donor liver transplantation in a patient with
      Wilson's disease: a case report.
AB  - A patient with end-stage liver cirrhosis and neurological disorder due to
      Wilson's disease (WD) underwent auxiliary partial orthotopic liver
      transplantation (APOLT) using a living donor. He first visited our institute
      complaining of hand tremor, which was diagnosed as WD. Despite medical therapy,
      hepatic impairment progressed toward portal hypertensive complications. He was
      considered a suitable candidate for living donor-related liver transplantation.
      However, because of the impossibility of mobilization of the lateral section due
      to severe splenomegaly at the time of the recipient operation, we performed an
      APOLT using a right lobe graft. After transplantation, he suffered hepatic vein
      stenosis and biliary stenosis, receiving interventional therapy. The remnant
      native liver volume decreased, and the volume of the graft increased serially
      after transplantation. At the time of reporting, the patient had a normal working
      life with normal serum ceruloplasmin level and without neurologic problems at 26
      months posttransplantation. APOLT may be a therapeutic option for patients with
      WD.

PMID- 19100499
TI  - Severe sirolimus-related inflammatory state anemia in an HIV+ liver transplant
      patient with calcineurin inhibitor renal insufficiency: a case report.
AB  - Although multifactorial anemia is common following orthotopic liver
      transplantation (OLT), the late introduction of sirolimus (SRL) has been
      associated with high rates of anemia, whose pathogenic mechanisms have not been
      fully studied. Herein we have described a case of severe anemia in an HIV+ OLT
      patient who was switched from calcineurin inhibitors (CNI) to SRL due to severe
      nephrotoxicity. After 22 weeks of SRL, hemoglobin levels dropped 4 g/dL to a
      nadir of 6.5 g/dL. After discarding other causes for anemia, we concluded that it
      displayed the features of anemia of a chronic inflammatory state (ACIS):
      decreased mean corpuscular volume (MCV), low serum iron despite high
      ferritinemia, and elevated fibrinogen and C-reactive protein (CRP) levels. SRL
      trough levels were never above the therapeutic range. After blood transfusions
      and erythropoietin (EPO) use, SRL was maintained within the lower range of
      therapeutic levels, with significant improvement in renal function. As described
      among kidney transplant recipients, SRL-related anemia in this HIV+ patient with
      CNI nephrotoxicity after OLT showed features of ACIS. Blood transfusions and EPO
      use allowed SRL maintenance.

PMID- 19100500
TI  - Intrahepatic cholangiocarcinoma arising in chronic viral hepatitis-associated
      cirrhosis: two transplant cases.
AB  - Hepatitis C virus (HCV) or hepatitis B virus (HBV)-related cirrhosis is known to
      be a risk factor for hepatocellular carcinoma (HCC). Recently, these viruses have
      been reported to have an etiologic role in the development of intrahepatic
      cholangiocarcinoma (ICC). Herein we have reported two cases of HCV- and HBV
      related cirrhosis with ICC in whom the pretransplant diagnosis was HCC. The
      patient with HCV cirrhosis, was a 47-year-old woman with a large nodule in the
      right lobe. The patient with HBV cirrhosis was a 45-year-old man with two
      nodules. Serum tumor marker levels, carcinoembryonic antigen (CEA),
      alphafetoprotein (AFP), and carbohydrate antigen 19-9 (CA 19-9) were determined
      before live donor liver transplantation (LDLT). The patient with HCV cirrhosis
      showed mildly elevated serum levels of AFP. The patient with HBV cirrhosis showed
      an elevated CA 19-9 level. On microscopic examination, all nodules exhibited
      typical morphological findings of adenocarcinoma. The patient with HCV cirrhosis
      developed brain metastases 4 years after LDLT. The patient with HBV cirrhosis is
      disease-free at 18 months after transplantation. In cirrhotic patients with
      active malignancy who are candidates for LDLT, ICC should be considered in the
      differential diagnosis. Although the literature is limited, selected patients
      with ICC may benefit from LDLT.

PMID- 19100501
TI  - False positive tardus-parvus waveforms after liver transplantation: a case of
      wide discrepancy between donor and recipient hepatic arteries mimicking
      anastomotic stenosis.
AB  - BACKGROUND: Parvus-tardus waveforms of the hepatic artery after liver
      transplantation usually indicate an arterial complication and severe impairment
      of hepatic arterial perfusion with a sensitivity of 91% and a specificity of
      99.1%. Thus, it has been emphasized that detection of such waveforms should
      prompt emergency angiography. MATERIALS AND METHODS: Arterial reconstruction
      during a liver transplantation was successfully accomplished by an end-to-end
      anastomosis, performing a "flute-spout" widening of the anastomosis with a 7/0
      prolene running suture between a small recipient proper hepatic artery and the
      donor common hepatic artery. RESULTS: On day 7 posttransplantation color Doppler
      ultrasonography revealed a parvus-tardus waveform pattern in the hepatic arterial
      flow. Computed tomographic (CT) angiography showed only a caliber discrepancy
      between the donor and recipient stumps, excluding an arterial stenosis or
      thrombosis. Since normal liver function persisted, the patient underwent routine
      follow-up. After 15 months the patient was alive and well; hepatic artery
      spectral waveforms were unchanged and liver functions were consistent with a mild
      hepatitis C virus (HCV) recurrence. CONCLUSIONS: This is a report of false
      positive tardus-parvus waveforms, due to a discrepancy between the donor and
      recipient arteries despite a wide anastomosis. Knowledge of technical
      reconstruction details may be helpful for correct interpretation of color Doppler
      findings. CT angiography should be considered before more invasive examinations.

PMID- 19100502
TI  - Following-up of a four-dose daclizumab induction therapy without calcineurin
      inhibitors in a liver transplantation recipient with severe renal dysfunction: a
      case report.
AB  - BACKGROUND: There is debate on the dose schedule and pharmacokinetics of
      daclizumab in liver transplant recipients. METHODS: A four-dose course of
      daclizumab was administered to a patient with severe renal dysfunction.
      Calcineurin inhibitor therapy initiation was delayed to 86 days
      posttransplantation. RESULTS: The patient is well as 480 days after
      transplantation. No rejection was observed. CONCLUSIONS: The result suggested the
      efficacy of our dose schedule, but it will be necessary to confirm it with
      further pharmacokinetic studies and more cases.

PMID- 19100503
TI  - Liver transplantation for metastatic sinonasal undifferentiated carcinoma: a case
      report.
AB  - Sinonasal undifferentiated carcinoma (SNUC) is a relatively newly described
      malignancy of the nasal cavity and paranasal sinuses with a reported 25% to 30%
      risk for distant metastases. We have reported herein the case of a patient who
      underwent orthotopic liver transplantation (OLT) for hepatic metastases of SNUC.
      At 13 months follow-up she is alive with no sign of local or distant-site
      recurrence. Despite the limited follow-up, the present case suggests that a long
      disease-free survival after primary surgery, absence of local-regional
      recurrence, and stability of disease after chemotherapy may represent selection
      criteria to refer patients for OLT. However, continued follow-up and larger
      series are necessary to test this hypothesis in the long-term and to assess the
      role of posttransplantation chemotherapy.

PMID- 19100504
TI  - Role of lipid emulsion administration in acute lung injury during liver
      transplant rejection: a case report.
AB  - We report the case of a 58-year-old woman who developed rejection and acute lung
      injury 10 days after an orthotopic liver transplantation while receiving total
      parenteral nutrition. Examination of bronchoalveolar lavage fluid revealed large
      lipid droplets in the alveolar macrophages. Intensification of the
      immunosuppressive therapy attenuated the liver allograft rejection followed by
      resolution of lung injury.

PMID- 19100505
TI  - Morgagni hernia presenting with bowel obstruction in a lung transplant recipient:
      case report.
AB  - Morgagni hernias are uncommon congenital diaphragmatic deficiencies that may
      remain asymptomatic till adulthood. We report a case of Morgagni hernia
      presenting with subacute bowel obstruction in a bilateral lung transplant
      recipient. This diaphragmatic deficiency was not evident during bilateral lung
      transplantation surgery via clamshell incision. To our knowledge this is the
      first report of a congenital defect evident after lung transplantation.

PMID- 19100506
TI  - Three new nonsense mutations of MLH1 and MSH2 genes in Korean families with
      hereditary nonpolyposis colorectal cancer.
AB  - Hereditary nonpolyposis colorectal cancer (HNPCC) (MIM #114500), also called
      Lynch syndrome, is an autosomal dominantly inherited cancer syndrome accounting
      for 1-5% of all colorectal cancer cases. In a study of three Korean families with
      HNPCC consistent with the revised Bethesda criteria, DNA testing revealed three
      novel HNPCC germline mutations in two genes: namely, MLH1, with an insertion
      resulting in a frameshift and a premature stop codon; MSH2, with a deletion at
      nucleotide 633, exon 3, which results in stop of translation at codon 213; and
      MSH2, with a deletion at nucleotide 1413, exon 9, resulting in a frameshift and a
      premature stop codon. In the first two families, there were splice mutations at
      c.2006-6 thymine to cytosine. The clinical implications of a frameshift mutation
      are discussed, along with the significance of common underlying splice mutations
      existing within families with HNPCC.

PMID- 19100507
TI  - Prognostic impact of chromosome alterations detected by FISH in Turkish patients
      with B-cell chronic lymphocytic leukemia.
AB  - The goal of this study was to evaluate the relation of chromosomal abnormalities
      detected by fluorescence in situ hybridization (FISH) in the prognosis of B-cell
      chronic lymphocytic leukemia (B-CLL) patients. We evaluated the common recurrent
      chromosomal aberrations in 79 B-CLL patients (51 men, 28 women; mean age 64.3+/
      1.2) by FISH analysis using 11q22.3 (ATM), 13q14.3 (13S319 and 13S25), CEP12, and
      17p13.1 (TP53) specific probes. Of the 79 patients analyzed by FISH, 40 or 50.6%
      had at least one aberration. In particular, 34 (43%) patients had a single
      abnormality and 6 (7.6%) patients had 2 abnormalities. The most frequent
      abnormality was 13q14.3 deletion, which was detected in 26 (32.9%) patients.
      Trisomy 12 was seen in 12 (15.2%) cases, and was followed by 17p13.1 (TP53)
      deletions and 11q22.3 (ATM) deletions in 6 (7.6%) and 4 (5.1%) patients,
      respectively. When the overall frequencies of these chromosomal aberrations were
      distributed according to RAI stages, the majority of patients with 13q14.3
      deletion (55%), trisomy 12 (70%), and ATM or TP53 deletions (66.7 %) were in
      advanced stages of disease (RAI II-IV). The overall survival durations in good,
      intermediate, and poor prognostic groups were 51+/-1.3, 50.9+/-8.6, and 12+/-3.3
      months, respectively. Our data suggests that FISH analysis of B-CLL patients
      provides important diagnostic, clinical, and prognostic information which may
      help clinicians assess the prognosis and make appropriate treatment decisions.

PMID- 19100508
TI  - Identification of DNA copy number aberrations associated with metastases of
      colorectal cancer using array CGH profiles.
AB  - It is important to estimate the biological characteristics of tumors, including
      the nodal status at the time of diagnosis for optimal treatment of individual
      cancer patients. Array-based comparative genomic hybridization (aCGH) was
      performed on 77 sporadic colorectal adenocarcinomas using a chip spotted with
      4030 BAC clones. The nodal status was compared with an aCGH profiles depicted
      using a combination of decision-tree classifier and a Self-Organizing Map (SOM)
      analysis. Node metastasis was not detected in any of the 6 poorly differentiated
      adenocarcinomas with a 3q loss. A SOM analysis following the decision-tree
      classification of the aCGH data allowed for the differentiation in chromosomal
      regions between high- and low-level decreases in the DNA copy number. Node
      metastasis was detected in all 5 tumors with the high-level decrease in DNA copy
      number at Xp, irrespective of the histological type. Node metastasis was also
      found exclusively in 6 tumors with increase in DNA copy number at the chromosomal
      region between 11q13.3 and 11q22.3. Copy number aberrations linked to nodal
      metastasis were identified more collectively by the combination of the decision
      tree classifier and a SOM analysis than by the conventional analysis method in
      aCGH analysis.

PMID- 19100509
TI  - High incidence of MGMT promoter methylation in primary glioblastomas without
      correlation with TP53 gene mutations.
AB  - O(6)-methylguanine DNA methyltransferase (MGMT) reduces cytotoxicity of
      therapeutic or environmental alkylating agents. MGMT promoter methylation has
      been associated with TP53 G: C to A:T transition mutations in various types of
      cancers, and with poor prognosis in patients who did not receive chemotherapy.
      Mutations of TP53 are more frequent in secondary than in primary glioblastoma,
      thus the expected MGMT promoter methylation was low in primary glioblastoma.
      Glioblastoma patients with MGMT promoter methylation showed better response to
      chemotherapy based on alkylating agents and longer survival than patients without
      MGMT methylation. We examined 32 primary glioblastomas, treated with radiotherapy
      and surgery, for TP53 mutation by direct sequencing and MGMT promoter methylation
      by methylation-specific PCR. MGMT promoter methylation and TP53 mutations were
      detected in 72% and 31% of primary glioblastoma, respectively. Although not
      statistically significant, the frequency of TP53 G:C to A:T mutations were higher
      in cases with (26%) than without (11%) MGMT promoter methylation (p=0.376). MGMT
      promoter methylation had no impact on patient survival. Our data indicate that
      MGMT promoter methylation occurs frequently in primary glioblastoma, but does not
      lead to G:C to A:T TP53 mutations, has no independent prognostic value and is not
      a predictive marker unless glioblastoma patients are treated with chemotherapy.

PMID- 19100510
TI  - Duplication and triplication of der(21)t(8;21)(q22;q22) in acute myeloid
      leukemia.
AB  - We report on two patients with complicons resulting in duplication
      der(21)t(8;21)(q22;q22), triplication in the form of isochromosome of
      der(21)t(8;21), and four copies of ETO-AML1 fusion. Duplication of der(21) was
      present at diagnosis as a minor cell population in one patient, while the
      presence of isoderivative (21)t(8;21) characterized the relapse cells of the
      second patient. Due to the rarity of these cases, literature search of other
      reported cases of complicons may be taken as evidence that duplication and
      triplication of ETO-AML1 may be a poor prognostic indicator, regardless of
      whether it is present at diagnosis or relapse.

PMID- 19100511
TI  - ATP2A3 gene is involved in cancer susceptibility.
AB  - The sarco/endoplasmatic reticulum calcium-ATPase (SERCA) translocates Ca(2+) from
      cytosol to the lumen of the ER and thus regulates Ca(2+) homeostasis,
      perturbations of which have been suggested to contribute to cancer. We have
      previously detected an increased number of alterations in the ATP2A2 gene in
      various cancer types and in the ATP2A3 gene in head and neck squamous cell
      carcinoma. Here, we further analyzed the ATP2A3 gene in colon, lung, and CNS
      cancers. We identified a statistically significant increase of alterations in
      each (colon cancer, p=0.0052, lung cancer, p=0.0026, CNS tumors, p=0.0045) cancer
      type, and all 3 types together (p=0.0016). Epigenetic study of the ATP2A3 gene
      indicated an unchanged methylation status, whereas expression of the ATP2A3 gene
      was normal for exon 14 mutations and reduced in connection with a nucleotide
      change in intron VI in all studied cancer types. Identification of a significant
      number of alterations in cancer patients suggests that ATP2A3 is involved in
      increased cancer susceptibility in humans. The mostly normal expression and
      methylation status of the ATP2A3 gene, as well as the absence of somatic
      alterations, further suggest that the ATP2A3 gene may not act as a classical
      tumor suppressor gene, but rather haplo-insufficiency of this gene may be enough
      to change the cell and tissue environment in such a way to predispose to cancer
      development.

PMID- 19100512
TI  - Complex t(2;21;8)(p12;q22;q22): a variant t(8;21) in a patient with acute myeloid
      leukemia (AML-M2).
AB  - Acute myeloid leukemia with maturation (AML-M2 based on the French-American
      British classification) is often accompanied by typical chromosomal changes such
      as t (8;21)(q22;q22). We report a case of a 31-year-old female with a positive
      RUNX1/CBFA2T1 (alias AML1/ETO) fusion gene and a karyotype with a
      t(2;21;8)(p12;q22;q22). Although variant translocations involving chromosome
      region 2p12 have never been reported before, we suppose this translocation may be
      responsible for the clinical manifestation and prognosis of this case. The role
      of this complex variant translocation, as well as the possible formation
      mechanism, prognostic factors, and morphologic changes are discussed.

PMID- 19100513
TI  - Transient abnormal myelopoiesis in a Down syndrome newborn followed by acute
      myeloid leukemia: identification of the same chromosomal abnormality in both
      stages.
AB  - A transient abnormal myelopoiesis was observed in a newborn with Down syndrome.
      Cytogenetic study revealed multiple oligoclonal abnormalities:
      47,XY,inv(6)(p23q21),+21c[3]/47,XY,der(7)t(1;7)(q25;p15),+21c[1]/47,XY,del(13)(q?
      ,+21c[1]/47,XY,+21c[15]. Ten months after the patient achieved remission, the
      transient abnormal myelopoiesis evolved to an acute megakaryoblastic leukemia.
      Cytogenetic study revealed only a single clonal abnormality,
      47,XY,der(7)t(1;7)(q25;p15),+21c, identical to one of the structural changes seen
      at birth. Sequence analysis of the GATA1 gene revealed a deletion-insertion
      mutation within the exon 2 introducing a stop codon after Arg 64. It may be that
      the der(7)t(1;7)(q25;p15) abnormality played some selective role in the
      development of acute megakaryoblastic leukemia in this patient. To our knowledge,
      the present case is unique in demonstrating a subclone with der(7)t(1;7)(q25;p15)
      evolving to acute leukemia.

PMID- 19100514
TI  - Acute promyelocytic leukemia with insertion of PML exon 7a and partial deletion
      of exon 3 of RARA: a novel variant transcript related to aggressive course and
      not detected with real-time polymerase chain reaction analysis.
AB  - We report the case of a 38-year-old man with acute promyelocytic leukemia (APL)
      showing a distinct breakpoint cluster region 2 (bcr2) variant transcript.
      Findings from bone marrow, cytogenetic, fluorescence in situ hybridization, and
      qualitative reverse transcriptase-polymerase chain reaction (RT-PCR) analyses
      were consistent with the diagnosis of APL. Although PCR products of size 841 bp
      and 984 bp were amplified from bone marrow specimen, the quantitative PCR (RQ
      PCR) findings were negative. Given the discrepancy in PCR results, sequencing of
      PCR products was performed to determine the detailed composition of these fusion
      transcripts. By cloning and sequencing, we discovered that these two bands were
      isoforms, in which one exon (exon 5, 144 bp) of the PML gene was spliced out of
      the smaller products (minor PCR products); one sequence (G) insertion and one
      base substitution (T-->C) of PML exon 4 generate a stop codon in the smaller
      fusion transcript. In addition, a search of the Ensembl database revealed that
      these variant PML/RARA fusion transcripts were composed of exon 7a insertion of
      the PML gene and partial deletion (46 bp) of exon 3 of the RARA gene, in addition
      to inserted sequences of intron 7 of PML and genomic sequence ATCT of unknown
      origin at the fusion junction site. Although the biological significance of most
      atypical transcripts remains unclear, sequence analysis of these atypical
      products should be performed, to reveal the composition of such a fusion
      transcript and elucidate the molecular mechanism.

PMID- 19100515
TI  - Inverted duplication dup(1)(q32q21) as sole aberration in lymphoid and myeloid
      malignancies.
AB  - Partial gains of chromosome 1q as isolated aberrations are rare occurrences in
      hematologic malignancies. A recent report of a sole duplication dup(1)(q21q32) in
      myelodysplastic syndrome (MDS) suggested an inferior prognosis. To further
      describe structural anomalies involving the 1q21 and 1q32 breakpoints, we present
      four cases with an inverted dup(1)(q32q21): three in B-cell precursor acute
      lymphoblastic leukemia (ALL) and one in MDS of the subtype refractory cytopenia
      with multilineage dysplasia and ringed sideroblasts. In all four cases, the
      aberration presented as the sole anomaly at diagnosis. In one of the ALL cases,
      relapse during chemotherapy, 5 months from diagnosis, was accompanied by clonal
      evolution; in another ALL case, early relapse appeared 51 days after allogeneic
      stem cell transplantation. Structural gains of 1q involving 1q32 and 1q21
      breakpoints can occur in different hematological malignancies. The isolated
      occurrence of the inverted dup(1)(q32q21) may be interpreted as a typical primary
      alteration in B-lineage ALL paving the way to acquisition of additional
      abnormalities. Identification of more cases could further clarify the role of 1q
      duplications with the q21 and q32 breakpoints in hematological malignancies and
      better define the prognosis associated with sole aberration in the single
      entities.

PMID- 19100516
TI  - ETV6/RUNX1 fusion lacking prognostic effect in pediatric patients with acute
      lymphoblastic leukemia.
AB  - A Brazilian sample of 58 patients with acute lymphoblastic leukemia has been
      prospectively followed up with the objective of evaluating evolution of disease.
      Age ranged from 6 months to 16 years. Of the 58 patients, 11 were positive and 47
      were negative for the ETV6/RUNX1 fusion (previously known as TEL/AML1). After a
      minimum follow-up period of 57 months, 2 of the ETV6/RUNX1(+) patients had died
      and 11 of the ETV6/RUNX1(-), for an overall survival of 77.6%. Among the 11
      ETV6/RUNX1(+) patients (age range, 2 years to 13 years 7 months), all achieved a
      complete remission; the average overall survival was 64.2 months and the average
      event-free survival was 61.7 months. Among the 47 ETV6/RUNX1(-) patients, 4 did
      not have a complete remission; the average overall survival was of 60.8 months
      and the average event-free survival was 57.2 months. No significant difference
      was observed between overall survival and event-free survival, nor in any of the
      other data comparatively analyzed. The patients had a cure rate similar to that
      described in literature. In this small sample population, the presence of the
      ETV6/RUNX1 fusion did not identify statistical difference in prognosis.

PMID- 19100517
TI  - Deletion 15q as the sole abnormality in acute myeloid leukemia: report of three
      cases and review of the literature.
AB  - Deletions within the long arm of chromosome 15, a recurrent abnormality in
      myeloid malignancies, have been reported previously as a sole abnormality in only
      eight cases of acute myeloid leukemia (AML). We describe three new cases of AML
      with this abnormality, all adult women (age, 41-66 years). Two cases were acute
      myelomonocytic leukemia (FAB AML-M4), and one was acute myeloblastic leukemia
      with maturation (FAB AML-M2). The deletion was identified at initial diagnosis in
      one patient and at relapse in the other two. Although all received aggressive
      therapy, their survival was short. Taken together with the eight previously
      reported cases, we conclude that deletions in chromosome 15 are associated with
      AML, both in cases that arise de novo or in the setting of a myeloproliferative
      disorder or myelodysplastic syndrome. These cases often show features of
      myelomonocytic or monocytic differentiation. The prognosis is poor, with survival
      similar to other AML cases with unfavorable cytogenetic changes.

PMID- 19100518
TI  - A novel t(11;14)(q23;q32) in a case of myelodysplastic syndrome.

PMID- 19100519
TI  - TP53 mutations but no CHEK2 *1100DelC variant in familial gliomas.

PMID- 19100520
TI  - Biphenotypic acute leukemia with b2a2 fusion transcript and trisomy 21.

PMID- 19100521
TI  - Tel/PDGFRbeta induces stem cell differentiation via the Ras/ERK and STAT5
      signaling pathways.
AB  - OBJECTIVE: Fusion genes involving the platelet-derived growth factor receptor
      beta (PDGFRbeta) are found in a subgroup of myeloproliferative neoplasms, with
      one such fusion, Tel/PDGFRbeta found in a subset of chronic myelomonocytic
      leukemia patients. Tel/PDGFRbeta results in constitutive activation of several
      signaling pathways and induces a myeloproliferative disease in mice, with signals
      via tyrosines 579/581 identified as being important for this phenotype. In this
      study, we have used a tetracycline-regulated system to express wild-type and the
      mutated F2 Tel/PDGFRbeta to identify the key signaling pathways, which drive
      Tel/PDGFRbeta-induced differentiation of embryonic stem (ES) cells. MATERIALS AND
      METHODS: The leukemic oncogene Tel/PDGFRbeta and Tel/PDGFRbeta-F2 were inducibly
      expressed in ES cells and their effects on self-renewal, signal transduction, and
      gene expression patterns analyzed. RESULTS: Tel/PDGFRbeta activated several major
      signal transduction pathways (signal transducers and activators of transcription
      [STAT] 3, STAT5, mitogen-activated protein kinases, phosphatidylinositol-3
      kinase) in ES cells, but only specific inhibition of the mitogen-activated
      protein kinase kinase/extracellular regulated kinase (MEK/ERK) or STAT5 pathways
      was able to significantly prevent Tel/PDGFRbeta-induced differentiation and
      restore ES-cell self-renewal. Inhibiting the tyrosine kinase activity of the
      oncogene using Gleevec or PDGFRbeta inhibitor III also substantially prevented
      Tel/PDGFRbeta-induced differentiation and its ability to upregulate key genes
      involved in myelopoiesis. Tyrosines 579/581 played a critical role in mediating
      signals via the Ras/ERK and STAT5 pathways, with dual targeting of the tyrosine
      kinase activity of Tel/PDGFRbeta and the MEK/ERK pathway completely preventing
      Tel/PDGFRbeta-induced differentiation. CONCLUSION: These findings suggest that
      targeted disruption of key signaling pathways in combination with the tyrosine
      kinase activity of leukemic oncogenes, such as Tel/PDGFRbeta, may result in more
      efficacious therapies for suppressing leukemic progression in the clinical
      setting.

PMID- 19100522
TI  - A proapoptotic signaling pathway involving RasGRP, Erk, and Bim in B cells.
AB  - OBJECTIVE: Bryostatin-1 and related diacylglycerol (DAG) analogues activate
      RasGRPs in lymphocytes, thereby activating Ras and mimicking some aspects of
      immune receptor signaling. To define the role of RasGRPs in lymphocyte apoptosis
      and to identify potential therapeutic uses for DAG analogues in lymphocyte
      disorders, we characterized the response of lymphoma-derived cell lines to DAG
      analogues. MATERIALS AND METHODS: Human lymphoma-derived B cell lines and mouse
      primary B cells were treated with bryostatin-1 or its synthetic analogue "pico."
      Ras signaling partners and Bcl-2 family members were studied with biochemical
      assays. Cellular responses were monitored using growth and apoptosis assays.
      RESULTS: Stimulation of B cells with DAG analogues results in activation of
      protein kinase C/RasGRP-Ras-Raf-Mek-Erk signaling and phosphorylation of the
      proapoptotic BH3-only protein Bim. In vitro, Bim is phosphorylated by Erk on
      sites previously associated with increased apoptotic activity. In Toledo B cells
      derived from a non-Hodgkin's lymphoma (B-NHL), DAG analogue stimulation leads to
      extensive apoptosis. Apoptosis can be suppressed by either downregulation of Bim
      or overexpression of Bcl-2. It is associated with the formation of Bak-Bax
      complexes and increased mitochondrial membrane permeability. Toledo B-NHL cell
      apoptosis shows a striking dependence on sustained signaling. CONCLUSION: In B
      cells, Erk activation leads directly to phosphorylation of Bim on sites
      associated with activation of Bim. In Toledo B-NHL cells, the dependence of
      apoptosis on sustained signaling suggests that Bcl-2 family members could
      interpret signal duration, an important determinant of B cell receptor-mediated
      negative selection. Certain cases of B-NHL might respond to DAG analogue
      treatment by the mechanism outlined here.

PMID- 19100523
TI  - Quantitative monitoring of NPM1 mutations provides a valid minimal residual
      disease parameter following allogeneic stem cell transplantation.
AB  - BACKGROUND: Minimal residual disease (MRD) diagnostics in acute myeloid leukemia
      (AML) gain increasing importance after allogeneic stem cell transplantation
      (SCT). Nucleophosmin (NPM1) mutations, with their high frequency in AML, were
      suggested to represent suitable MRD markers, but so far no study has evaluated
      their usefulness in the posttransplantation period. MATERIALS AND METHODS: We
      evaluated the validity of this MRD marker in the posttransplantation period in a
      cohort of 13 patients with an NPM1A mutation (NPM1Amut). For this most frequent
      NPM1A subtype, quantitative real-time polymerase chain reaction (qPCR) was
      retrospectively performed on bone marrow/peripheral blood samples that had been
      taken before and after SCT. RESULTS: NPM1Amut was retrospectively followed up in
      13 patients who received 14 transplantations. One-hundred and thirty-nine qPCR
      analyses were performed (median: 7 time points; median follow-up: 216 days;
      range, 35-1825 days). After SCT, 10 of 14 NPM1Amut cases (71%) became PCR
      negative, of which four achieved stable remissions. All four patients (29%) who
      remained NPM1Amut-positive after SCT relapsed. In all nine relapse cases,
      increases of NPM1Amut were seen that preceded morphological relapse and the
      decrease of molecular chimerism with mean intervals of 24 days (range, 12-38
      days) and 15 days (range, 1-36 days), respectively. CONCLUSIONS: Quantitative
      assessment of NPM1Amut seems to provide a reliable MRD marker in the
      posttransplantation period, predicting relapse earlier than morphology or
      molecular chimerism, which should be confirmed in larger studies.

PMID- 19100524
TI  - Investigation of immunological approaches to enhance engraftment in a 1 Gy TBI
      canine hematopoietic stem cell transplantation model.
AB  - OBJECTIVE: Stable mixed hematopoietic chimerism can be established in a canine
      stem cell transplantation model using a conditioning consisting of total body
      irradiation (TBI; 2 Gy) and postgrafting immunosuppression with mycophenolate
      mofetil (MMF) and cyclosporin (CSA). Reduction of TBI had resulted previously in
      graft rejection in this model. We investigated whether postgrafting stimulation
      of donor T cells against recipient's hematopoietic antigens or graft augmentation
      with donor monocyte-derived dendritic cells (MoDC) promote engraftment following
      1 Gy TBI. MATERIALS AND METHODS: All dogs received dog leukocyte-antigen
      identical bone marrow transplantation. Dogs were conditioned with either 2 Gy TBI
      (group 1) or 1 Gy TBI, followed by repetitive recipient hematopoietic cell lysate
      vaccinations (group 2) or graft augmentation with MoDC (group 3).
      Immunosuppression consisted of CSA and MMF. RESULTS: In group 1, four animals
      remained stable chimeras for >110 weeks, and three rejected their grafts (week
      10, week 14, week 16). All dogs in groups 2 and 3 rejected their graft (median:
      week 10 and 11, respectively). Peak chimerism and engraftment duration was
      shorter in the 1-Gy groups (p < 0.05) compared to group 1. CONCLUSION: Neither
      postgrafting vaccination nor graft augmentation with MoDC were effective in
      supporting durable engraftment. Additional modifications are necessary to improve
      potential strategies aimed at establishment of early tissue specific graft-vs
      host reactions.

PMID- 19100525
TI  - Emotional state and local versus global spatial memory.
AB  - The present work investigated the effects of participant emotional state on
      global versus local memory for map-based information. Participants were placed
      into one of four emotion induction groups, crossing high and low arousal with
      positive and negative valence, or a control group. They then studied a university
      campus map and completed two memory tests, free recall and spatial statement
      verification. Converging evidence from these two tasks demonstrated that arousal
      amplifies symbolic distance effects and leads to a globally-focused spatial
      mental representation, partially at the expense of local knowledge. These results
      were found for both positively- and negatively-valenced affective states. The
      present study is the first investigation of emotional effects on spatial memory,
      and has implications for theories of emotion and spatial cognition.

PMID- 19100527
TI  - Effectiveness of vertical visual reference for reducing postural instability on
      inclined and compliant surfaces at elevation.
AB  - Falls from elevation continue to be the most serious hazard for the workers in
      construction. Simple and cost effective technical approaches to improve workers'
      balance on sloped roofs and deformable/unstable platforms have potential to
      reduce the risk of falls. This study evaluated the effectiveness of simple
      vertical structures as visual references (cue) for balance improvement. Twenty
      four construction workers were tested while standing on sloped and deformable
      surfaces at elevation and performing undemanding visual tasks with vertical
      structures positioned at different proximal locations. Workers' balance
      performance was assessed by sway parameters calculated from the center-of
      pressure movement collected with a force platform. The study results indicate
      increased instability on the sloped and deformable surfaces at elevation, and
      show that a simple vertical structure, e.g., a narrow bar, can serve as a visual
      cue and assist workers' balance. Workers' balance improved linearly with cue
      proximity in the tested distance range both on the sloped and the deformable
      surfaces. At a moment of instability, workers can redirect their attention to a
      proximal structure, available in the line of sight, to assist balance control.
      These findings may be useful in modifying elevated work environments and
      construction procedures to improve workers' postural balance during various
      construction phases.

PMID- 19100526
TI  - Genetic defects in surfactant protein A2 are associated with pulmonary fibrosis
      and lung cancer.
AB  - Idiopathic pulmonary fibrosis (IPF) is a lethal scarring lung disease that
      affects older adults. Heterozygous rare mutations in the genes encoding
      telomerase are found in approximately 15% of familial cases. We have used linkage
      to map another disease-causing gene in a large family with IPF and adenocarcinoma
      of the lung to a 15.7 Mb region on chromosome 10. We identified a rare missense
      mutation in a candidate gene, SFTPA2, within the interval encoding surfactant
      protein A2 (SP-A2). Another rare mutation in SFTPA2 was identified in another
      family with IPF and lung cancer. Both mutations involve invariant residues in the
      highly conserved carbohydrate-recognition domain of the protein and are predicted
      to disrupt protein structure. Recombinant proteins carrying these mutations are
      retained in the endoplasmic reticulum and are not secreted. These data are
      consistent with SFTPA2 germline mutations that interfere with protein trafficking
      and cause familial IPF and lung cancer.

PMID- 19100528
TI  - ERP correlates of processing native and non-native language word stress in
      infants with different language outcomes.
AB  - The early acquisition of native language prosody is assumed to ease infants'
      language development. In a longitudinal setting we investigated whether the early
      processing of native and non-native language word stress patterns is associated
      with children's subsequent language skills. ERP data of 71 four- and five-month
      old infants were retrospectively grouped according to children's verbal
      performance in a language test at 2.5 years. Children who displayed age-adequate
      expressive language skills later in development showed both an early and a late
      negative mismatch response (MMR) when processing the native language stress
      pattern as deviant in a passive oddball design. Children with poor language
      skills later in development did not show these negativities. Both groups
      displayed an infant-specific positive MMR to the non-native language deviant.
      This positivity was enhanced and prolonged in children who showed poor language
      skills later in development as compared to children who showed normal language
      skills. The results indicate that variability in expressive language development
      has precursors in infants' ERP correlates of word stress processing.

PMID- 19100529
TI  - Granit's retina.

PMID- 19100530
TI  - Sperm viability, apoptosis, and intracellular reactive oxygen species levels in
      human spermatozoa before and after induction of oxidative stress.
AB  - OBJECTIVE: To investigate sperm viability, incidence of apoptosis, and
      intracellular basal and induced reactive oxygen species (ROS) in sperm fractions.
      DESIGN: Prospective controlled study. SETTING: Center for Reproductive Medicine
      at a tertiary care hospital. METHOD(S): Liquefied seminal ejaculates (n = 12)
      prepared by density gradient centrifugation were reconstituted to 2 mL with
      phosphate-buffered saline. Oxidative stress was induced by hydrogen peroxide
      (H(2)O(2), 100 muM). Sperm viability, intracellular ROS, and incidence of
      apoptosis/necrosis in neat, immature, and mature sperm fractions were assessed.
      RESULT(S): Before H(2)O(2) exposure, mature spermatozoa fractions showed a
      significantly lower incidence of apoptotic sperm and intracellular O(2)(-*)
      levels but higher amounts of intracellular H(2)O(2) compared with neat semen.
      Higher levels of intracellular H(2)O(2) were demonstrated in immature sperm
      fractions compared with neat or mature fractions. In all sperm fractions,
      intracellular H(2)O(2) levels correlated with the intracellular concentration of
      O(2)(-*). After H(2)O(2) exposure, neat semen showed a significantly higher
      percentage of apoptosis compared with the prepared mature spermatozoa. However,
      no differences were observed in the incidence of apoptosis between immature and
      mature sperm fractions. CONCLUSION(S): There is a differential shift of both
      intracellular H(2)O(2) and O(2)(-*) in each sperm fraction that may affect sperm
      quality. Sperm apoptosis is related to intracellular H(2)O(2) levels, which in
      turn are affected by intracellular O(-*) levels. Oxidative stress was not
      associated with an increased incidence of apoptosis in immature or mature sperm
      fractions.

PMID- 19100531
TI  - Infertility service use among U.S. women: 1995 and 2002.
AB  - OBJECTIVE: To examine trends in use of medical services for infertility, by
      individual characteristics of women. DESIGN: Pooled data from two cycles (1995
      and 2002) of the National Survey of Family Growth, a periodically conducted,
      nationally representative, cross-sectional survey of women 15-44 years of age.
      PARTICIPANT(S): The analysis sample was composed of 2,005 women 22-44 years of
      age with current fertility problems. INTERVENTION(S): None. MAIN OUTCOME
      MEASURE(S): Ever having used infertility services, and highest level of services
      used. RESULT(S): Between 1995 and 2002, ever-use of infertility services by
      fertility-impaired women age 22-44 years continued to be closely associated with
      older age, nulliparity, formal marital status, and higher socioeconomic status
      (education, household income, and private health insurance). Net of these
      factors, race and Hispanic origin, showed no significant association with either
      the use of services overall or the highest level of services used. After
      controlling for compositional changes in these individual characteristics, a
      slight decline was seen in ever-use of services overall from 1995 to 2002. No
      effect of survey year was noted in the highest level of services. CONCLUSION(S):
      Infertility service use among fertility-impaired women remains closely tied with
      socioeconomic factors. The "threshold effect" of these factors has shifted upward
      to the receipt of more costly services such as assisted reproductive
      technologies. These higher level services remain a relatively small fraction of
      the services reported in a general population sample of fertility-impaired women.

PMID- 19100532
TI  - Characterizing the reproductive hormone milieu in infertile women with diminished
      ovarian reserve.
AB  - OBJECTIVE: To elucidate the reproductive hormone profiles in association with a
      diagnosis of diminished ovarian reserve (DOR). DESIGN: Prospective observational
      study. SETTING: Academic tertiary care infertility practice. PATIENT(S): Eight
      regularly cycling infertile women diagnosed with DOR as the underlying
      contributor to infertility and 14 age-comparable healthy controls.
      INTERVENTION(S): Daily morning urine voids were collected during one menstrual
      cycle. MAIN OUTCOME MEASURE(S): Urinary excretion of gonadotropins (FSH, LH) and
      metabolites of estrogen (E; estrone conjugate) and P (pregnanediol 3 glucoronide)
      during an entire menstrual cycle in women with DOR and healthy controls.
      RESULT(S): Women with DOR demonstrated significantly higher urinary FSH levels in
      the early follicular phase, exaggerated amplitudes, significantly protracted
      durations of LH, concomitant FSH surges, and significantly impaired luteal phase
      urinary excretions of estrone conjugate and pregnanediol 3 glucoronide compared
      with the controls. CONCLUSION(S): Women with DOR demonstrate reproductive hormone
      profiles that are distinct from age-comparable controls, share similarities with
      profiles previously described during menopause transition, as well as exhibit
      unique features not previously recognized in the context of reproductive aging.

PMID- 19100533
TI  - Antral follicle count is a significant predictor of livebirth in in vitro
      fertilization cycles.
AB  - In the first published demonstration that the antral follicle count (AFC)
      predicts live birth after in vitro fertilization-embryo transfer (IVF-ET), we
      found that an AFC of >or=11 was a strong positive predictor of live birth. The
      AFC should not be used to exclude women from IVF treatment; however, it is a very
      useful instrument for patient counseling and determining appropriate treatment
      protocols and gonadotropin dosing in IVF cycles.

PMID- 19100534
TI  - Dynamic changes of germinal vesicle chromatin configuration and transcriptional
      activity during maturation of rabbit follicles.
AB  - Dynamic changes in configuration of germinal vesicle (GV) chromatin and their
      effects on oocyte transcriptional activity and developmental competence were
      studied in rabbit oocytes. The results indicated that global condensation of GV
      chromatin, rather than the formation of a perinucleolar ring, would better
      reflect the global transcriptional repression and developmental competence of
      oocytes. Gonadotropins, by promoting large-scale chromatin remodeling, regulate
      oocyte transcriptional activity and developmental competence.

PMID- 19100535
TI  - Exogenous androstenedione induces formation of follicular cysts and premature
      luteinization of granulosa cells in the ovary.
AB  - OBJECTIVE: To investigate the effects of androstenedione on ovarian follicle
      development. DESIGN: Experimental study. SETTING: University research laboratory.
      ANIMAL(S): Female Wistar-Imamichi rats and BDF1 mice. INTERVENTION(S): Rats were
      injected with androstenedione. Ovarian follicles of mice were cultured in the
      presence of androstenedione. MAIN OUTCOME MEASURE(S): Ovarian morphology; ovarian
      cell types undergoing apoptosis; ovarian expression of cytochrome P450 aromatase
      (P450arom), cytochrome P450 side-chain cleavage (P450scc), and cyclin-dependent
      kinase inhibitor p27(kip1); serum levels of T, E(2), and P in rats; and
      ultrastructure of granulosa cells from cultured follicles of mice. RESULT(S): In
      androstenedione-treated rat ovaries, follicular cysts were formed, and apoptotic
      cells were found in the inner part of granulosa cell layers of antral follicles.
      Androstenedione administration down-regulated expression of P450arom but up
      regulated expression of P450scc and p27(Kip1) in the granulosa cells of antral
      follicles. Serum T levels were significantly increased in androstenedione-treated
      rats. In mouse follicles exposed to androstenedione, the granulosa cells
      contained abundant lipid droplets and mitochondria with complex tubular cristae.
      CONCLUSION(S): Excess androgen enhances apoptosis in the inner part of granulosa
      cell layers of antral follicles, resulting in the formation of follicular cysts.
      It is also demonstrated that androgen stimulates premature luteinization of
      granulosa cells.

PMID- 19100536
TI  - Infrared digital telethermography: a new method for early detection of
      varicocele.
AB  - Besides physical examination, various traditional methods of examination are
      believed to have an important role in diagnosing varicocele. Infrared digital
      telethermography is presented as a new diagnostic tool for early presentation of
      varicocele.

PMID- 19100537
TI  - Human papillomavirus found in sperm head of young adult males affects the
      progressive motility.
AB  - OBJECTIVE: To evaluate the prevalence of human papillomavirus (HPV) sperm
      infection and its correlation with sperm parameters in a cohort of young adult
      males. DESIGN: Cross-sectional clinical study. SETTING: Andrology and
      Microbiology sections at a university hospital. PATIENT(S): A cohort of 200 young
      adult male volunteers (18 years old), 100 with previous sexual intercourse and
      100 without previous sexual intercourse. MAIN OUTCOME MEASURE(S): Seminal
      parameters, sperm culture for HPV and fluorescence in situ hybridization (FISH)
      analysis for HPV detection in the sperm head. Statistical analysis was performed
      with a two-tailed Student's t-test. RESULT(S): Results of HPV investigation were
      compared to sperm parameters and results of FISH analysis. HPV infection was
      present in sperm cells of 10 subjects among those 100 young adults who already
      had unprotected intercourse and its presence was associated with reduced sperm
      motility. Furthermore, infected samples showed that about 25% of sperm had an HPV
      DNA positivity at the head site, but it is unclear whether it was integrated in
      the nucleus or not. CONCLUSION(S): This is the first report estimating the
      percentage of HPV-positive sperm in infected subjects and the association between
      HPV infection and sperm motility.

PMID- 19100538
TI  - Infertility and bilateral adrenal tumors.
AB  - An infertile man who presents with azoospermia and bilateral adrenal tumors
      reveals an XX karyotype and congenital adrenal hyperplasia due to 21-hydroxylase
      deficiency. Hysterectomy and bilateral oophorectomy performed in infancy and lack
      of treatment resulted in full masculinization.

PMID- 19100539
TI  - Male infertility related to an aberrant karyotype, 46,XY,9ph,9qh+.
AB  - OBJECTIVE: To report a man with primary infertility and variant karyotype.
      DESIGN: Case report. SETTING: Private practice. PATIENT(S): A 37-year-old man
      with 4 years of primary infertility due to oligoasthenozoospermia.
      INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): G- and C-banding. Polymerase
      chain reaction for SRY, DBY, RBMY, DAZ, AMELX, and AMELY. RESULT(S): G-band
      analysis of the proband revealed a 46,XY,9ph,9qh+ karyotype. C-banding confirmed
      increase in the heterochromatin in one chromosome 9 and inversion in the other.
      CONCLUSION(S): The morphologic difference between the homologous chromosomes 9
      may have been responsible for an error in crossing-over, leading to aberrant
      spermatozoa and consequently to infertility.

PMID- 19100540
TI  - Extensive tissue damage of bovine ovaries after bipolar ovarian drilling compared
      to monopolar electrocoagulation or carbon dioxide laser.
AB  - OBJECTIVE: To evaluate the size of ovarian damage caused by ovarian drilling in
      polycystic ovary syndrome, the amount of inflicted damage was assessed for the
      most frequently used ovarian drilling techniques. DESIGN: Experimental
      prospective design. SETTING: University clinic. PATIENT(S): Six fresh bovine
      ovaries per technique. INTERVENTION(S): Carbon dioxide (CO(2)) laser, monopolar
      electrocoagulation, and bipolar electrocoagulation were used for in vitro ovarian
      drilling. MAIN OUTCOME MEASURE(S): Amount of inflicted ovarian damage per
      procedure. RESULT(S): Bipolar electrocoagulation resulted in significantly more
      destruction per burn than the CO(2) laser and monopolar electrocoagulation (287.6
      versus 24.0 and 70.0 mm(3), respectively). The damage found per lesion was
      multiplied by the regularly applied number of punctures per procedure in daily
      practice (based on the literature). Again, the bipolar electrocoagulation
      resulted in significantly more tissue damage than the CO(2) laser and monopolar
      coagulation (2,876 versus 599 and 700 mm(3), respectively). CONCLUSION(S):
      Ovarian drilling, especially bipolar electrocoagulation, causes extensive
      destruction of the ovary. Given the same clinical effectiveness of the various
      procedures, it is essential to use the lowest possible dose that works; thus, the
      first choice should be CO(2) laser or monopolar electrocoagulation.

PMID- 19100541
TI  - Assessment of axillary nerve function and functional outcome after fixation of
      complex proximal humeral fractures using the extended deltoid-splitting approach.
AB  - BACKGROUND AND PURPOSE: The extended deltoid-splitting approach was developed as
      an alternative to the deltopectoral approach in the treatment of three- and four
      part proximal humeral fractures. The aim of our prospective study was to
      determine whether this approach was associated with evidence of nerve injury,
      functional deficits or other complications in these cases, during the first year
      following reconstruction. METHODS: Over a 1-year-period, we treated 14 people
      (median age 59 years) with open reduction and plate fixation using the extended
      deltoid-splitting approach. All were prospectively reviewed clinically and
      radiologically during the first year after surgery. Functional testing involved
      three scoring systems, spring balance testing of deltoid power, dynamic muscle
      function testing and, at 1 year, electrophysiological assessment of axillary
      nerve function. RESULTS: Of the 14 fractures, 13 united without complications and
      with comparatively minor residual functional deficits. Of these 13 cases, 1
      showed slight neurogenic change in the anterior deltoid but no evidence of
      anterior deltoid paralysis. In the remaining case, osteonecrosis of the humeral
      head developed 9 months after surgery and functional scores were poor, but
      without evidence of nerve injury on electrophysiological testing. CONCLUSIONS:
      This technique is a useful alternative in the treatment of complex proximal
      humeral fractures, providing good access for reduction and implant placement
      without adverse effects.

PMID- 19100543
TI  - Comment on: "Missed injury and the tertiary trauma survey" [Injury 2008; 39:107
      114].

PMID- 19100542
TI  - Hip fractures after falls in hospital: a retrospective observational cohort
      study.
AB  - OBJECTIVES: To compare the prevalence and characteristics of hip fractures
      sustained after inpatient falls (hospital subgroup) to those presenting with a
      fall in the community (control group). DESIGN: Retrospective observational cohort
      study. SETTING: University teaching hospital. PARTICIPANTS: 5879 hip fractures
      occurred over an 8-year period, 327 of these took place after a fall as a
      hospital inpatient. OUTCOME MEASURES: Comparison of 30-day and 1 year mortality,
      co-morbidities, length of post-fracture hospital stay, specific complication
      rates and cognitive function between the hospital and control group. Other
      specific data on those falling in hospital was also collected. RESULTS: There
      were significantly higher rates (p<0.001) of cerebrovascular, chronic obstructive
      airways and renal disease, diabetes, malignancy and polypharmacy in patients
      suffering falls in hospital. Mini-mental test scores (MTS) were also
      significantly reduced in this subgroup (p<0.001). 30-day and 1 year mortality
      rates were 9% and 26%, respectively in the control group and almost double this
      in the hospital subgroup, being 18% and 47%, respectively (30 days, 95% CI 2.00
      (1.54-2.60): p<0.001; 1 year, 95% CI 2.04 (1.73-2.40): p<0.001). There was no
      statistical difference between post-operative complications or length of stay
      post-fracture. 55% of falls in hospital took place on medical/geriatric wards
      with an additional 14% occurring on psychiatric units. DISCUSSION: Patients
      suffering hip fractures after falls in hospital are frailer with impaired
      cognitive function and have more co-morbidities than those suffering a fracture
      in the community. These patients have increased mortality, with almost 50% dead
      within 1 year of the fall. The majority of hip fractures after falls occur in
      medical or geriatric wards, but the highest risk group appears to be elderly
      patients on psychiatric wards. Therefore, falls risk assessment and falls
      prevention schemes in hospital elderly patients are of paramount importance.

PMID- 19100544
TI  - Humeral head necrosis rate at mid-term follow-up after open reduction and angular
      stable plate fixation for proximal humeral fractures.
AB  - INTRODUCTION: Short-term follow-up of angular stable fixation for proximal
      humeral fractures has been well documented in the literature. Longer follow-up
      series are difficult to find. However, especially regarding the risk of avascular
      humeral head necrosis longer follow-up series are high of clinical relevance.
      METHODS: Forty-eight patients with a mean age of 66 years and treated with open
      reduction and angular stable internal fixation for proximal humeral fractures
      were followed up for a mean of 45 months. The clinical and radiographic follow-up
      (Constant Score (CS), age and gender related Constant Score (agCS), Constant
      Score in comparison to the contralateral side (%CS) and shoulder anterior
      posterior and lateral view and axial view X-rays) was performed postoperatively.
      RESULTS: Clinical results after 45 months showed a mean CS of 66.2+/-15.4 points
      with a mean agCS of 90.0+/-23.1%. Evaluation of the %CS showed 77.7+/-17.8%. %CS
      results showed no significant differences after 45 months in comparison to those
      obtained after 12 months. However, incidence of avascular necrosis of the humeral
      head doubled over the follow-up period from 4 cases at 12 months follow-up to 9
      cases at final follow-up. CONCLUSION: Results of open reduction and internal
      fixation with angular stable implants for proximal humeral fractures are
      reliable, however long-term complications such as avascular necrosis of the
      humeral head need to be evaluated further on since its incidence increases over
      the time.

PMID- 19100545
TI  - Stable fixation of distal clavicle fracture with comminuted superior cortex using
      oblique T-plate and cerclage wiring.

PMID- 19100546
TI  - Utilization of analgesics, sedatives, and pain scores in infants with a prolonged
      hospitalization: a prospective descriptive cohort study.
AB  - AIM: Describe the utilization of analgesic and sedative medications and
      documentation of pain scores in a cohort of critically ill infants in a neonatal
      intensive care unit. METHOD: A prospective, longitudinal, cohort study of infants
      with a predicted length of stay > or =28 days. Dosages and routes of
      administration of analgesic and sedative medications and documentation of pain
      scores were collected on a daily basis. RESULTS: 55 infants were enrolled into
      the study. Oral sucrose was administered to all 55 infants, 51 infants (93%) were
      administered enteral acetaminophen and 50 (91%) infants were administered
      morphine during their hospitalization. Sedatives were administered to 42 infants
      (76%); 36 (65%) were administered chloral hydrate and 32 (58%) were administered
      intravenous midazolam. With the exception of the first week of admission, when
      there was highest utilization of opioids and lower use of sucrose, acetaminophen
      and sedatives, the pattern of administration of analgesic and sedative agents
      remained relatively constant throughout the hospitalization. Pain scores were
      documented for 36 (65%) infants during their hospitalisation, however for these
      36 infants, pain scores were infrequently recorded. CONCLUSION: There was
      substantial and varied analgesic and sedative use in this cohort of infants, yet
      infrequent documentation of pain assessment scores. These practices highlight
      important clinical implications for sick infants requiring careful consideration
      of pain and distress management.

PMID- 19100547
TI  - Asymmetric and symmetric dimethylarginines are of similar predictive value for
      cardiovascular risk in the general population.
AB  - OBJECTIVES: Asymmetric dimethylarginine (ADMA) has raised considerable interest,
      as it is an endogenous inhibitor of nitric oxide synthesis. While increased
      plasma levels of ADMA have been reported in different cardiovascular disease
      states, its association with symmetric dimethylarginine (SDMA) has not been
      evaluated in a prospective population-based study. METHODS AND RESULTS: We
      performed a mass spectrometry-based analysis of ADMA and SDMA in the plasma of
      572 participants of the Bruneck study. Levels of ADMA and SDMA were significantly
      correlated with each other (r=0.189, p<0.001). Age and parameters of renal
      function, however, showed a stronger influence on SDMA than on ADMA. Both ADMA
      and SDMA were predictive of cardiovascular disease in multivariate analysis and
      the associated hazard ratios over the 5-year observation period were of similar
      strength: 3.86 (1.36-10.9) and 7.91 (1.94-32.3) for ADMA and SDMA, respectively
      (p=0.011 and 0.004). Separate analyses focused on quintile groups of SDMA
      revealed that the increase in cardiovascular risk was mainly confined to the top
      category (>0.80 micromol/L). CONCLUSION: This study argues against an exclusive
      ADMA effect in mediating cardiovascular risk. Instead, SDMA, its supposedly
      inactive counterpart, has similar diagnostic value in this large prospective
      cohort.

PMID- 19100548
TI  - Elevation of systemic PLTP, but not macrophage-PLTP, impairs macrophage reverse
      cholesterol transport in transgenic mice.
AB  - Phospholipid transfer protein (PLTP) is a multifunctional protein synthesized by
      various cell types and secreted into the plasma. Plasma PLTP is able to transfer
      phospholipids between lipoproteins and modulate HDL particles. Mice with
      overexpression of human PLTP have an increased ability to generate pre beta-HDL,
      reduced total HDL levels and an increased susceptibility to atherosclerosis. As
      the macrophage is a key component of the atherosclerotic lesion and an important
      site of PLTP expression, we investigated the role of systemic and peripheral PLTP
      in macrophage cholesterol efflux and reverse cholesterol transport (RCT) in vivo.
      We used an assay in which (3)H-labelled cholesterol-loaded macrophages were
      injected intraperitoneally into recipient mice, and radioactivity was quantified
      in plasma, liver and faeces. Firstly, wild type macrophages were injected into
      wild type, PLTP transgenic (PLTPtg) and apoAI transgenic (apoAItg) mice. While
      plasma (3)H-tracer levels in apoAItg mice were increased compared with wild type
      mice, they were reduced in PLTPtg mice. Moreover, overexpression of PLTP
      significantly decreased faecal (3)H-tracer levels compared with wild type and
      apoAItg mice. Secondly, wild type mice were injected with peritoneal macrophages
      derived from PLTPtg or wild type mice. No significant difference in the amount of
      (3)H-tracer in plasma, liver or faeces was found between the two groups of mice.
      Our findings demonstrate that macrophage cholesterol efflux and RCT to faeces is
      impaired in PLTP transgenic mice, and that elevation of macrophage-PLTP does not
      affect RCT, indicating that higher systemic PLTP levels may promote
      atherosclerosis development by decreasing the rate of macrophage RCT.

PMID- 19100549
TI  - Hypertension and cerebrovascular damage.
AB  - Hypertension is the most important modifiable factor for cerebrovascular disease.
      Stroke and dementia are growing health problems that have considerable social and
      economical consequences. Hypertension causes brain lesions by several mechanisms
      predisposing to lacunar infarctions, leucoaraiosis, and white matter changes as
      well as to intracerebral haemorrhages. These parenchymal damages determine
      evident or silent neurological alterations that often precede the onset of
      cognitive decline. It is important to recognize cerebrovascular disease and,
      above all, to correlate typical lesions to hypertension. Antihypertensive therapy
      has shown clinical benefits in primary and secondary prevention of stroke. These
      drugs represent important instruments against cerebrovascular disease but their
      effects on cognition are still matter of debate. Cerebral parenchymal and
      functional damages have to be considered together to make medical intervention
      more incisive.

PMID- 19100550
TI  - The effect of isolated valgus moments on ACL strain during single-leg landing: a
      simulation study.
AB  - Valgus moments on the knee joint during single-leg landing have been suggested as
      a risk factor for anterior cruciate ligament (ACL) injury. The purpose of this
      study was to test the influence of isolated valgus moment on ACL strain during
      single-leg landing. Physiologic levels of valgus moments from an in vivo study of
      single-leg landing were applied to a three-dimensional dynamic knee model,
      previously developed and tested for ACL strain measurement during simulated
      landing. The ACL strain, knee valgus angle, tibial rotation, and medial
      collateral ligament (MCL) strain were calculated and analyzed. The study shows
      that the peak ACL strain increased nonlinearly with increasing peak valgus
      moment. Subjects with naturally high valgus moments showed greater sensitivity
      for increased ACL strain with increased valgus moment, but ACL strain plateaus
      below reported ACL failure levels when the applied isolated valgus moment rises
      above the maximum values observed during normal cutting activities. In addition,
      the tibia was observed to rotate externally as the peak valgus moment increased
      due to bony and soft-tissue constraints. In conclusion, knee valgus moment
      increases peak ACL strain during single-leg landing. However, valgus moment alone
      may not be sufficient to induce an isolated ACL tear without concomitant damage
      to the MCL, because coupled tibial external rotation and increasing strain in the
      MCL prevent proportional increases in ACL strain at higher levels of valgus
      moment. Training that reduces the external valgus moment, however, can reduce the
      ACL strain and thus may help athletes reduce their overall ACL injury risk.

PMID- 19100551
TI  - Biomechanical study of grasping according to the volume of the object: human
      versus non-human primates.
AB  - The evolution of the precision grips, in which an object is held between the
      distal surfaces of thumb and fingers and the power grip, in which an object is
      grasped with the palm, is poorly understood in spite of hypothesis stipulating an
      evolution from power toward precision grips. In human, numerous studies have
      shown that the external factors such as the size or the form of an object
      influenced grasp patterns whereas in non-human primates, those parameters are
      poorly known. The objective of the present study was to investigate the variation
      in the use of different grips according to the volume of the object for six
      primate species representative of the phylogeny: human, chimpanzee, orangutan,
      macaque, baboon and capuchin. For those species, the grasping patterns were
      examined during grasping of spherical objects of two different volumes. Frame-by
      frame analysis of digit contact strategies indicated: (1) an effect of the
      species on the category of grasping whatever the volume of the object, (2) a high
      degree of species variability and (3) no individual difference whatever the
      species. These results are discussed in relation to its potential contribution to
      understand the evolution of grasping.

PMID- 19100552
TI  - Development of fluorinated, monolithic columns for improved chromatographic
      separations of fluorous-tagged analytes.
AB  - With applications that take advantage of highly selective fluorine-fluorine
      interactions appearing with greater frequency in the literature, the development
      of porous polymer monoliths from fluorous components is reported here for the
      purpose of chromatography of tagged analytes. With potential uses in fields as
      diverse as separation science and proteomics, facile fabrication of materials
      with fluorous specificity that can be applied in a high-throughput manner is
      greatly desirable. To this end, we have developed porous polymer capillary
      columns with varied fluorous content using a simple UV-initiated radical
      polymerization process and characterized them using flow-induced backpressure and
      scanning electron microscopy (SEM). With structural similarities assured
      (visually, and by backpressure variations of less than 42%), the monoliths were
      tested as chromatographic columns for the separation of a series of fluorous
      tagged analytes under gradient conditions. It was found that columns made with
      fluorinated components exhibited greater selectivity for fluorous analytes than
      did equivalent, non-fluorinated monoliths, retaining analytes with either one or
      two fluorous tags for approximately 6% and 13% longer, respectively. This
      supports the idea of differences existing between fluorous and reverse-phase
      separation mechanisms, and encourages a broader range of potential applications
      for fluorous monoliths of this type.

PMID- 19100553
TI  - Methods of calculating protein hydrophobicity and their application in developing
      correlations to predict hydrophobic interaction chromatography retention.
AB  - Hydrophobic interaction chromatography (HIC) is a key technique for protein
      separation and purification. Different methodologies to estimate the
      hydrophobicity of a protein are reviewed, which have been related to the
      chromatographic behavior of proteins in HIC. These methodologies consider either
      knowledge of the three-dimensional structure or the amino acid composition of
      proteins. Despite some restrictions; they have proven to be useful in predicting
      protein retention time in HIC.

PMID- 19100554
TI  - Effect of phenyl sepharose ligand density on protein monomer/aggregate
      purification and separation using hydrophobic interaction chromatography.
AB  - In the large-scale manufacturing and purification of protein therapeutics,
      multiple chromatography adsorbent lots are often required due to limited
      absorbent batch sizes or during replacement at the end of the useful column
      lifetime. Variability in the adsorbent performance from lot to lot should be
      minimal in order to ensure that consistent product purity and product quality
      attributes are achieved when a different lot or lot mixture is implemented in the
      process. Vendors of chromatographic adsorbents will often provide release
      specifications, which may possess a narrow range of acceptable values. Despite
      relatively narrow release specifications, the performance of the adsorbent in a
      given purification process could still vary from lot to lot. In this case, an
      alternative use test (one that properly captures the lot to lot variability) may
      be required to determine an acceptable range of variability for a specific
      process. In this work, we describe the separation of therapeutic protein monomer
      and aggregate species using hydrophobic interaction chromatography, which is
      potentially sensitive to adsorbent lot variability. An alternative use test is
      formulated, which can be used to rapidly screen different adsorbent lots prior to
      implementation in a large-scale manufacturing process. In addition, the
      underlying mechanism responsible for the adsorbent lot variability, which was
      based upon differences in protein adsorption characteristics, was also
      investigated using both experimental and modeling approaches.

PMID- 19100555
TI  - Gas chromatography-mass spectrometry screening methods for select UV filters,
      synthetic musks, alkylphenols, an antimicrobial agent, and an insect repellent in
      fish.
AB  - Two screening methods have been developed for simultaneous determination of ten
      extensively used personal care products (PCPs) and two alkylphenol surfactants in
      fish. The methods consisted of extraction, clean-up, derivatization and analysis
      by gas chromatography-mass spectrometry with selected ion monitoring (GC-SIM-MS)
      or gas chromatography-tandem mass spectrometry (GC-MS/MS) techniques. Among
      solvents tested to assess recovery of target compounds from 1-g tissue
      homogenates, acetone was selected as optimal for extracting compounds with
      dissimilar physicochemical properties from fish tissue. Initial experiments
      confirmed that GC-SIM-MS could be applied for analysis of lean fillet tissue (<1%
      lipid) without gel-permeation chromatography (GPC), and this approach was applied
      to assess the presence of target analytes in fish fillets collected from a
      regional effluent-dominated stream in Texas, USA. Benzophenone, galaxolide,
      tonalide, and triclosan were detected in 11 of 11 environmental samples at
      concentrations ranging from; 37 to 90, 234 to 970, 26 to 97, and 17 to 31 ng/g,
      respectively. However, performance of this analytical approach declined
      appreciably with increasing lipid content of analyzed tissues. Successful
      analysis of samples with increased lipid content was enabled by adding GPC to the
      sample preparation protocol and monitoring analytes with tandem mass
      spectrometry. Both analytical approaches were validated using fortified fillet
      tissue collected from locations expected to be minimally impacted by
      anthropogenic influences. Average analyte recoveries ranged from 87% to 114% with
      RSDs <11% and from 54% to 107% with RSDs <20% for fish tissue containing <1% and
      4.9% lipid, respectively. Statistically derived method detection limits (MDLs)
      for GC-SIM-MS and GC-MS/MS methodologies ranged from 2.4 to 16 ng/g, and 5.1 to
      397 ng/g, respectively.

PMID- 19100557
TI  - Analysis of capsaicin and dihydrocapsaicin in peppers and pepper sauces by solid
      phase microextraction-gas chromatography-mass spectrometry.
AB  - A simple method for the analysis of capsaicin and dihydrocapsaicin in peppers and
      pepper sauces by solid phase microextraction-gas chromatography-mass spectrometry
      has been developed. A novel device was designed for direct extraction solid phase
      microextraction in order to avoid damage to the fiber. The analysis was performed
      without derivatization for the gas chromatography-mass spectrometry analysis.
      Selection fiber, extraction temperature, extraction time and pH, were optimized.
      The method was linear in the range 0.109-1.323 microg/mL for capsaicin and 0.107
      1.713 microg/mL for dihydrocapsaicin with correlation coefficient up to r=0.9970
      for both capsaicinoids. The precision of the method was less than 10%. The method
      was applied to the analysis of 11 varieties of peppers and four pepper sauces. A
      broad range of capsaicin (55.0-25 459 microg/g) and dihydrocapsaicin (93-1 130
      microg/g) was found in the pepper and pepper sauces samples (4.3-717.3 and 1.0
      134.8 microg/g), respectively.

PMID- 19100558
TI  - Thermosensitive and pH-sensitive Au-Pd bimetallic nanocomposites.
AB  - The bimetallic nanoparticles were protected by a double stimuli-sensitive diblock
      copolymer, poly(N-isopropylacrylamide)-block-poly(4-vinylpyridine) (PNIPAM-b
      P4VP), which was synthesized via the reversible addition-fragmentation chain
      transfer (RAFT) polymerization. The obtained nanocomposites were made up of
      bimetallic nanoparticles cross-linked P4VP core and PNIPAM shell. Energy
      dispersive X-ray (EDX) spectra and UV-vis transmittance revealed the formed
      nanoparticles was truly bimetallic particles with incomplete core-shell
      structures, Au as core and Pd as shell, rather than the physical mixture of
      monometallic nanoparticles. Laser light scattering (LLS) demonstrated the
      nanocomposites exhibit both thermo and pH sensitivity. X-ray diffraction (XRD)
      clearly showed Au formed a high-ordered crystal while Pd fashioned amorphous
      aggregates. In addition, the bimetallic nanocomposites show special
      responsiveness for temperature and better catalytic activity than corresponding
      monometallic nanocomposites.

PMID- 19100559
TI  - Effect of anchoring group on the photosensitization of colloidal TiO2
      nanoparticles with porphyrins.
AB  - The interaction of porphyrins (TCPP, TSPP, TMeOPP and TPP) with colloidal TiO(2)
      nanoparticles was studied by infra-red, UV-visible absorption, steady state and
      time resolved fluorescence spectroscopy. The porphyrins (TCPP, TSPP and TMeOPP)
      adsorbed on the surface of colloidal TiO(2) nanoparticles through electrostatic
      interaction. According to absorption and fluorescence changes the apparent
      association constants (K(app)) were calculated. However, TPP did not interact
      with surface of colloidal TiO(2) nanoparticles due to the absence of anchoring
      group. The fluorescence quenching is attributable mainly to electron transfer
      from the excited state porphyrins to the conduction band of colloidal TiO(2). The
      rate of electron transfer process (k(et)) was calculated using lifetime
      measurement. The electron transfer mechanism has been proved by the calculation
      of free energy change (DeltaG(et)) by applying Rehm-Weller equation. Using all
      the spectroscopic measurements we confirmed that the presence of anchoring group
      plays major role in the adsorption as well as the electron transfer processes.

PMID- 19100560
TI  - Magnetoviscosity of dilute suspensions of magnetic ellipsoids obtained through
      rotational Brownian dynamics simulations.
AB  - The magnetic field dependent viscosity (magnetoviscosity) of dilute suspensions
      of magnetic tri-axial ellipsoidal particles suspended in a Newtonian fluid and
      under applied shear and magnetic fields was studied numerically. Brownian
      dynamics simulations were performed to compute the intrinsic magnetoviscosity of
      the suspension. Results are presented for the response of dilute suspensions of
      ellipsoidal particles to constant magnetic and shear flow fields. Suspensions of
      ellipsoidal particles show a significant effect of aspect ratio on the intrinsic
      magnetoviscosity of the suspension, and this effect is more pronounced as the
      aspect ratio becomes more extreme. The use of an effective rotational diffusion
      coefficient D(r,eff) collapses the normalized intrinsic magnetoviscosity of all
      suspensions to a master curve as a function of Peclet number with the Langevin
      parameter alpha=(mu(0)muH)/(k(B)T) as parameter, up to a critical value of alpha
      for which the results for suspensions of spherical particles deviate from those
      of suspensions of ellipsoids. This discrepancy is attributed to the action of the
      shear-torque on the ellipsoidal particles, which tends to orient these particles
      in the direction of maximum deformation of the simple shear flow, and which does
      not act on spherical particles.

PMID- 19100556
TI  - Effect of the matrix on DNA electrophoretic mobility.
AB  - DNA electrophoretic mobilities are highly dependent on the nature of the matrix
      in which the separation takes place. This review describes the effect of the
      matrix on DNA separations in agarose gels, polyacrylamide gels and solutions
      containing entangled linear polymers, correlating the electrophoretic mobilities
      with information obtained from other types of studies. DNA mobilities in various
      sieving media are determined by the interplay of three factors: the relative size
      of the DNA molecule with respect to the effective pore size of the matrix, the
      effect of the electric field on the matrix, and specific interactions of DNA with
      the matrix during electrophoresis.

PMID- 19100561
TI  - Fabrication of robust honeycomb polymer films: a facile photochemical cross
      linking process.
AB  - Highly ordered honeycomb films are prepared by breath-figure method using an
      amphiphilic diblock copolymer of polystyrene-block-polyacrylic acid (PS-b-PAA).
      By simply cross-linking PS matrix via deep ultraviolet (UV) irradiation, both the
      solvent and thermal stability of the porous films was significantly improved
      while retaining the three-dimensional (3D) structures. The film surface
      wettability was changed from hydrophobicity to hydrophilicity by the formed polar
      groups during the photochemical process. After 6 h UV cross-linking, the
      honeycomb structures could be preserved up to 320 degrees C, an increase of more
      than 200 K as compared to the non-cross-linked films.

PMID- 19100562
TI  - Acute anteroseptal myocardial infarction in a patient with dextrocardia.
AB  - Dextrocardia with situs inversus is an uncommon congenital condition in which the
      major visceral organs are reversed. The clinical diagnosis and
      electrocardiographic localization of myocardial infarctions in these patients
      remain a great challenge. We report a case of a 64-year-old man known with
      dextrocardia and situs inversus totalis presenting with acute chest pain
      irradiating to the right arm. The admission and reversed "normalized"
      electrocardiogram are presented, allowing for correct diagnosis of an acute
      anteroseptal myocardial infarction. The present case emphasizes the importance of
      performing a reversed electrocardiogram in patients with dextrocardia.

PMID- 19100563
TI  - Proximal right coronary artery occlusion with ST elevation in all precordial
      leads.
AB  - We present a case of a 55-year-old-man with acute coronary syndrome due to
      occlusion of the right coronary artery. Electrocardiogram showed ST-segment
      elevation in nine leads. We explain the causes of this exceptional
      electrocardiographic pattern.

PMID- 19100564
TI  - Antiarrhythmic actions of growth hormone during acute myocardial infarction.

PMID- 19100565
TI  - EASI-Derived vs standard 12-lead electrocardiogram for Selvester QRS score
      estimations of chronic myocardial infarct size, using cardiac magnetic resonance
      imaging as gold standard.
AB  - BACKGROUND: The size of myocardial infarction (MI) is of significance for the
      prognosis. Selvester scores might be valuable for this estimation. OBJECTIVE: To
      compare the differences in Selvester scores for chronic MI provided from standard
      and EASI-derived 12-lead electrocardiograms (ECGs) and to compare these scores to
      the MI size measured by delayed-enhancement magnetic resonance imaging (DE-MRI).
      METHODS: Thirty-seven patients were studied. In connection with their DE-MRI scan
      follow-up after chest pain, body surface potential mapping was performed.
      Standard and EASI 12-lead ECGs were constructed from the maps. Two investigators
      manually performed the measurements required for scoring with the Selvester
      system using a quad-plot format of the ECGs. One of the investigators repeated
      this once for the standard leads. RESULTS: The differences between the 2 ECG
      estimations of MRI-measured MI size were not statistically significant. Neither
      the association nor the agreement between MRI and EASI-lead measurements or
      between MRI and standard-lead measurements were very strong. CONCLUSIONS: The
      differences between ECG and MRI measurements of MI size indicate that both
      methods may need improvement.

PMID- 19100566
TI  - Location of myocardium at risk in patients with first-time ST-elevation
      infarction: comparison among single photon emission computed tomography, magnetic
      resonance imaging, and electrocardiography.
AB  - BACKGROUND: The amount of myocardium at risk (MaR) during acute coronary
      occlusion and the duration of occlusion are important determinants of final
      infarct size. The main goal of early reperfusion therapy is to salvage ischemic
      myocardium, thereby preserving left ventricular function. The aims of the present
      study were to test the feasibility of developing polar plot representations of
      MaR, for perfusion single photon emission computed tomography (SPECT), regional
      wall thickening by magnetic resonance imaging (MRI), and distribution of ST
      segment changes. A second aim was to test the hypothesis that these different
      modalities display similar localization of the MaR in patients with reperfused
      first-time myocardial infarction. METHODS: Eleven patients with first-time
      myocardial infarction with ST-elevation received (99m)Tc tetrofosmin before
      primary percutaneous coronary intervention, SPECT imaging within 3 hours, and
      cardiac MRI of the left ventricle within 24 hours. The results for SPECT, MRI,
      and electrocardiogram (ECG) were developed into polar plots, and two expert
      observers designated the culprit coronary artery as assessed by angiography.
      RESULTS: The perfusion SPECT, MRI wall thickening, and ST changes are presented
      in side-by-side polar plots. In total, the culprit artery, based on the location
      of the MaR, was correctly designated in 91%, 82%, and 91% of cases by SPECT, MRI,
      and ECG, respectively. CONCLUSIONS: Polar representation for localization of the
      MaR by SPECT perfusion, MRI wall thickening, and ECG ST-segment deviation is
      feasible. All 3 modalities have the potential to be used for indirect visual
      designation of the culprit artery in patients with first-time acute coronary
      occlusion.

PMID- 19100567
TI  - The accuracy of multidetector computerized tomography for evaluating tumor
      thrombus in patients with renal cell carcinoma.
AB  - PURPOSE: New advances in computerized tomography, including multidetector
      computerized tomography with 3-dimensional reformatting has recently called into
      question the absolute need for magnetic resonance imaging for evaluating renal
      cell carcinoma with suspected venous involvement. We assessed the accuracy of
      multidetector computerized tomography for predicting tumor thrombus and the level
      of venous involvement in patients with renal cell carcinoma. MATERIALS AND
      METHODS: We retrospectively reviewed clinical and pathological features in 41
      patients with renal cell carcinoma who underwent staging multidetector
      computerized tomography before surgery. Multidetector computerized tomography
      findings regarding the presence and level of tumor thrombus were compared to
      findings at surgery and at final pathological evaluation. All multidetector
      computerized tomography studies were read by a single radiologist (EKF) before
      surgery. RESULTS: When excluding patients with segmental venous involvement only,
      the concordance rate between multidetector computerized tomography and
      pathological findings was 84%. Multidetector computerized tomography accurately
      predicted the level of tumor thrombus in 26 of 27 patients (96%). Four cases of
      negative multidetector computerized tomography findings were up staged to renal
      vein involvement based on pathological findings. All 4 patients had early distal
      thrombi that did not change operative management. CONCLUSIONS: Multidetector
      computerized tomography with 3-dimensional mapping is an effective imaging
      modality for accurately characterizing the level of venous thrombus in patients
      with renal cell carcinoma. This modality effectively identified patients with
      clinically significant venous thrombus. Patients with renal cell carcinoma in
      whom multidetector computerized tomography fails to detect tumor thrombus are
      unlikely to have a tumor thrombus found at surgery that would change the surgical
      approach.

PMID- 19100568
TI  - Preoperative prognostic nomogram (probability table) for renal cell carcinoma
      based on TNM classification.
AB  - PURPOSE: Recently several prognostic nomograms have been developed to predict the
      prognosis of malignant diseases, including renal cell carcinoma. However, to our
      knowledge a preoperative prognostic nomogram that predicts survival in patients
      with renal cell carcinoma is not available. We developed a preoperative nomogram
      based on the TNM classification that predicts cause specific survival in patients
      with renal cell carcinoma. MATERIALS AND METHODS: A total of 545 patients with
      renal cell carcinoma, including metastatic disease, who underwent radical
      nephrectomy or nephron sparing surgery at our institution were included in the
      study. Cases were staged according to the 2002 UICC TNM system, 6th edition. T, N
      and M factors were used as prognostic factors and a Cox proportional hazards
      regression model was developed to predict cause specific survival. A nomogram to
      predict cause specific survival was developed by repeating the analysis on 200
      bootstrap samples. To validate the nomogram a concordance index was estimated and
      calibration was also examined by plotting the predictions made by the nomogram.
      RESULTS: Overall 1, 3 and 5-year patient survival was 95.2%, 92.0% and 89.9%,
      respectively. T, N and M factors were significant prognostic factors in the Cox
      proportional hazards regression model. Using the combined TNM factors we
      developed a nomogram predicting 1, 3 and 5-year cause specific survival rates.
      The nomogram had excellent ability to discriminate, as evidenced by a concordance
      index of 0.81, and it was generally well calibrated. CONCLUSIONS: The
      preoperative information shown by this nomogram may be important for obtaining
      informed consent from patients with renal cell carcinoma who have indications for
      surgery.

PMID- 19100570
TI  - Predictors of survival of advanced renal cell carcinoma: long-term results from
      Southwest Oncology Group Trial S8949.
AB  - PURPOSE: S8949 demonstrated improved overall survival for debulking nephrectomy
      in interferon treated patients with advanced renal cell carcinoma. We present an
      updated analysis of S8949, now with a median followup of 9 years. We explored
      clinical predictors of overall survival. MATERIALS AND METHODS: Univariate and
      multivariate Cox regression analysis was performed to evaluate the impact of
      clinical variables potentially influencing survival. RESULTS: Of 246 patients 241
      were eligible and randomized to interferon with or without nephrectomy. Patients
      randomized to nephrectomy continued to have improved overall survival (HR 0.74,
      95% CI 0.57-0.96, p = 0.022). Multivariate analysis showed that performance
      status 1 vs 0 (HR 1.95, p <0.0001), high alkaline phosphatase (HR 1.5, p = 0.002)
      and lung metastasis only (HR 0.73, p = 0.028) were overall survival predictors.
      There was no evidence of an interaction of performance status, measurable disease
      or lung metastases with nephrectomy (each p >0.30). In a patient subset that
      survived at least 90 days after randomization early progressive disease within 90
      days was prognostic of overall survival in a multivariate model (HR 2.1, p
      <0.0001), as was performance status (HR 1.7, p = 0.0006). CONCLUSIONS:
      Nephrectomy prolonged long-term overall survival in this updated analysis,
      supporting its role as standard therapy in patients with advanced renal cell
      carcinoma. A nephrectomy benefit was seen across all prespecified patient
      subsets. Early progressive disease and performance status were strong predictors
      of overall survival. These results support efforts to identify biomarkers of
      renal cell carcinoma resistance to treatment and early progressive disease to
      facilitate rational patient selection for systemic therapy.

PMID- 19100573
TI  - Radiation exposure in the acute and short-term management of urolithiasis at 2
      academic centers.
AB  - PURPOSE: Diagnostic imaging has a central role in the evaluation and management
      of urolithiasis. A variety of modalities are available, each with benefits and
      limitations. Without careful consideration of imaging modalities in quantity and
      type patients may receive excessive doses of radiation during initial diagnostic
      and followup evaluations. Therefore, we determined the effective radiation dose
      associated with an acute stone episode and short-term followup. MATERIALS AND
      METHODS: A multicenter retrospective study of all patients who presented with an
      acute stone episode was performed. The analysis included all imaging studies
      related to stone disease performed within 1 year of the acute event. Using
      accepted effective radiation dose standards for each of these examinations, the
      total radiation dose administered was calculated and compared by patient
      characteristics including stone location, stone number and intervention strategy.
      The primary outcome assessed was a total radiation dose greater than 50 mSv, the
      recommended yearly dose limit for occupational exposure by the International
      Commission on Radiological Protection. RESULTS: We identified 108 patients who
      presented to our respective institutions with a primary acute stone episode
      between 2000 and 2006. The mean age in our cohort was 48.6 years and 50% of the
      patients were men. Patients underwent an average of 4 radiographic examinations
      during the 1-year period. Studies performed included a mean of 1.2 plain
      abdominal films of the kidneys, ureters and bladder (range 0 to 7), 1.7
      abdominopelvic computerized tomograms (range 0 to 6) and 1 excretory urogram
      (range 0 to 3) during the first year of followup. The median total effective
      radiation dose per patient was 29.7 mSv (IQR 24.2, 45.1). There were 22 (20%)
      patients who received greater than 50 mSv. Analysis of stone location, number of
      stones, stone composition, patient age, sex and surgical intervention indicated
      no statistically significant difference in the probability of receiving a total
      radiation dose greater than 50 mSv. CONCLUSIONS: A fifth of patients receive
      potentially significant radiation doses in the short-term followup of an acute
      stone event. Radiographic imaging remains an integral part of the diagnosis and
      management of symptomatic urolithiasis. While debate exists regarding the
      threshold level for radiation induced fatal malignancies, urologists must be
      cognizant of the radiation exposure to patients, and seek alternative imaging
      strategies to minimize radiation dose during acute and long-term stone
      management.

PMID- 19100576
TI  - Diagnostic accuracy of transitional cell carcinoma on multidetector computerized
      tomography urography in patients with gross hematuria.
AB  - PURPOSE: We analyzed the diagnostic value of multidetector computerized
      tomography urography for transitional cell carcinoma in patients with gross
      hematuria. MATERIALS AND METHODS: All consecutive adult patients with gross
      hematuria who underwent multidetector computerized tomography urography in a 23
      month period were prospectively enrolled. Transitional cell carcinoma and its
      location on multidetector computerized tomography urography were recorded at a
      prospective reading with knowledge of the pertinent history and at a
      retrospective reading while blinded to all information. Histological evidence of
      transitional cell carcinoma served as the gold standard for final diagnosis.
      Patients who were lost to followup, refused biopsy/surgery for clinically
      suspicious neoplasms or had negative diagnostic evaluation but a followup of less
      than 1 year were excluded from study. We analyzed the diagnostic value of
      multidetector computerized tomography urography for transitional cell carcinoma
      by location with reference to final diagnosis. RESULTS: A total of 139 patients
      were eligible for study, of whom 24 were excluded from analysis. There was no
      difference in demographic features between included and excluded patients. Of the
      115 included patients 60 had a final diagnosis of a total of 77 transitional cell
      carcinomas in the renal pelvis, ureter or bladder. Overall sensitivity,
      specificity and accuracy of multidetector computerized tomography urography for
      diagnosing transitional cell carcinoma were 0.857, 0.980 and 0.963 at the
      retrospective reading, and 0.961, 0.988 and 0.984 at the prospective reading,
      respectively. Multidetector computerized tomography urography had the highest
      accuracy for diagnosing renal transitional cell carcinoma and the lowest
      sensitivity for detecting ureteral transitional cell carcinoma. CONCLUSIONS:
      Multidetector computerized tomography urography is an accurate, noninvasive
      imaging modality for diagnosing transitional cell carcinoma in patients with
      gross hematuria. However, careful assessment of the ureter for multidetector
      computerized tomography urography is required for detecting ureteral transitional
      cell carcinoma.

PMID- 19100579
TI  - Response of the primary tumor to neoadjuvant sunitinib in patients with advanced
      renal cell carcinoma.
AB  - PURPOSE: We assessed the activity of neoadjuvant sunitinib on primary renal
      tumors in patients with advanced renal cell carcinoma as well as the feasibility
      and safety of subsequent surgical resection. METHODS: A total of 19 patients with
      advanced renal cell carcinoma deemed unsuitable for initial nephrectomy due to
      locally advanced disease or extensive metastatic burden were treated with 50 mg
      sunitinib daily for 4 weeks on followed by 2 weeks off. Tumor response was
      assessed by Response Evaluation Criteria in Solid Tumors every 2 cycles and the
      rate of conversion to resectable status was estimated. RESULTS: Median patient
      age was 64 years and initial median radiographic renal tumor size was 10.5 cm.
      Clinical stage was N+ (10) and M+ (15). No patients experienced a complete
      response. Partial responses of the primary tumor were noted in 3 patients (16%),
      7 (37%) had stable disease and 9 (47%) had disease progression in the primary
      tumor. Overall tumor response included 2 patients (11%) with partial response, 7
      (37%) with stable disease and 10 (53%) with disease progression. At a median
      followup of 6 months (range 1 to 15) 4 patients (21%) had undergone nephrectomy
      and 5 died of disease progression. No unexpected surgical morbidity was
      encountered. Viable tumor was present in all 4 specimens. Sunitinib was
      associated with grade 3-4 toxicity in 7 patients (37%) and treatment was
      discontinued in 1 due to toxicity. CONCLUSIONS: Administration of sunitinib in
      patients with advanced renal cell carcinoma with the primary tumor in place is
      feasible and can lead to a reduction in tumor burden that can facilitate
      subsequent surgical resection.

PMID- 19100580
TI  - Prostate cancer severity among low income, uninsured men.
AB  - PURPOSE: The proportion of American men with organ confined, low risk prostate
      cancer has increased significantly during the last 2 decades. Whether this trend
      also applies to men at the extremes of socioeconomic disadvantage remains
      unknown. Therefore, we evaluated trends in prostate cancer severity in an
      ethnically diverse cohort of low income, uninsured men served by a state funded
      public health program in California. MATERIALS AND METHODS: We performed a
      retrospective cohort study of 570 disadvantaged men enrolled in the California
      program from 2001 through 2006. Using routinely collected clinical variables we
      defined 2 measures of cancer severity as 1) the proportion of enrollees with
      metastases at diagnosis and 2) the proportions of men with nonmetastatic tumors
      whose cancers had low, intermediate or high risk features at diagnosis. We
      performed bivariate analyses to assess time trends in cancer severity. RESULTS:
      Prostate specific antigen levels at diagnosis exceeded 10 ng/ml for 51% of
      enrollees, 50% had a Gleason score 7 or greater and 43% had clinical T stage T2
      or greater. Of disadvantaged men 19% had metastatic cancer at diagnosis and this
      proportion remained stable over time (p = 0.66). Among men with nonmetastatic
      cancers 24% had tumors with low risk features and the proportion of low risk
      cancers did not increase over time (p = 0.34). CONCLUSIONS: Unlike the broader
      United States population the proportion of disadvantaged men with organ confined,
      low risk prostate cancer has not been increasing. Thus, while much attention
      focuses on potential overdiagnosis and overtreatment of men with screen detected
      prostate cancer, our findings suggest that for low income, uninsured men,
      underdetection and undertreatment remain significant concerns.

PMID- 19100583
TI  - Clam farmers and Oystercatchers: effects of the degradation of Lanice conchilega
      beds by shellfish farming on the spatial distribution of shorebirds.
AB  - The Manila clam Ruditapes philippinarum cultivation is an original shellfish
      farming activity strongly mechanized. In the Chausey archipelago (France) this
      activity settles on the Lanice conchilega beds, habitat known to host a rich and
      diversified benthic macrofauna and which is an attractive feeding ground for
      birds. A first study highlighted that this activity had strong negative effects
      on the L. conchilega beds and their associated benthic macrofauna. Here we assess
      the impacts of such an activity on the Eurasian Oystercatcher Haematopus
      ostralegus for which Chausey is one of the most important national breeding sites
      and which is also a common species in winter, spring and autumn migrations. We
      found that Oystercatchers significantly selected the L. conchilega beds to feed
      and that their spatial distribution was significantly modified after the creation
      of new clam concessions. In a context of a growing disappearance of pristine
      coastal ecosystems for the benefit of anthropo-ecosystems, we discuss the problem
      of the degradation of such benthic habitats with a low resilience which may loose
      their high functional value.

PMID- 19100584
TI  - Trace metals in antifouling paint particles and their heterogeneous contamination
      of coastal sediments.
AB  - Antifouling paint residues collected from the hard-standings of a marine leisure
      boat facility have been chemically characterised. Scanning electron microscopy
      revealed distinct layers, many containing oxidic particles of Cu and Zn.
      Quantitative analysis indicated concentrations of Cu and Zn averaging about 300
      and 100 mg g(-1), respectively, and small proportions of these metals (<2%) in
      organometallic form as pyrithione compounds. Other trace metals present included
      Ag, Cd, Cr, Ni, Pb and Sn, with maximum concentrations of about 330, 75, 1200,
      780, 1800 and 25,000 microg g(-1), respectively. Estuarine sediment collected
      near a boatyard contained concentrations of Cu and Zn an order of magnitude
      greater than respective concentrations in "background" sediment, and mass balance
      calculations suggested that the former sample was contaminated by about 1% by
      weight of paint particles. Clearly, antifouling residues represent a highly
      significant, heterogeneous source of metallic contamination in the marine
      environment where boating activities occur.

PMID- 19100585
TI  - Monitored and modeled coral population dynamics and the refuge concept.
AB  - With large-scale impacts on coral reefs due to global climatic change projected
      to increase dramatically, and suitability of many areas for reef growth projected
      to decrease, the question arises whether particular settings might serve as
      refugia that can maintain higher coral populations than surrounding areas. We
      examine this hypothesis on a small, local scale in Honduras, western Caribbean.
      Dense coral thickets containing high numbers of the endangered coral Acropora
      cervicornis occur on offshore banks while being rare on the fringing reef on
      nearby Roatan. Geomorphological setting and community dynamics were evaluated and
      monitored from 1996 to 2005. A model of population dynamics was developed to test
      assumptions derived from monitoring. Coral cover on the fringing reef declined in
      1998 from >30% to <20%, but the banks maintained areas of very dense coral cover
      (32% cover by A. cervicornis on the banks but <1% on the fringing reef).
      Bathymetry from satellite images showed the banks to be well-separated from the
      fringing reef, making asexual connectivity between banks and fringing reef
      impossible but protecting the banks from direct land-runoff during storms.
      Exposure to SE tradewinds also causes good flushing. Only four A. cervicornis
      recruits were recorded on the fringing reef over 6 years. Runoff associated with
      hurricanes caused greater mortality than did bleaching in 1998 and 2005 on the
      fringing reef, but not on the banks. Since 1870, our analysis suggests that
      corals on the banks may have been favored during 17 runoff events associated with
      tropical depressions and storms and potentially also during five bleaching
      events, but this is more uncertain. Our model suggests that under this
      disturbance regime, the banks will indeed maintain higher coral populations than
      the fringing reef and supports the assumption that offshore banks could serve as
      refugia with the capacity to subsidize depleted mainland populations.

PMID- 19100586
TI  - [Study of the junction between the cortical bridging veins and basal cranial
      venous sinus].
AB  - INTRODUCTION: The cerebral venous system is poorly known and is best appreciated
      based on macroscopic anatomical considerations. We present an anatomical and
      immunohistochemical study to better define the morphological characteristics of
      the junction between the inferior cortical veins and the transversal sinuses.
      MATERIAL AND METHODS: Sixteen cadaveric specimens from the anatomy laboratory of
      the University Victor-Segalen of Bordeaux were studied. The venous junctions with
      the transversal sinuses were observed under the operating microscope. Thirty vein
      sinus junctions were immunohistochemically stained with smooth muscle actin. Ten
      venous junctions were observed under the electronic microscope. RESULTS: The
      inferior cortical veins drain into the transverse sinus either directly or
      through a tentorial sinus. The venous orifices in the transverse sinuses share
      the same characteristics. They are oval with semicircular superior dural
      reinforcement and follow an orientation opposite venous flow in the transversal
      sinus. The histologic study showed that the walls of the cortical veins contained
      smooth muscle cells as well as the dural reinforcement of the transversal
      sinuses. CONCLUSION: The venous orifices of the inferior cortical veins have the
      anatomical features of true sphincters. Their function in the regulation of the
      cerebral blood flow needs further exploration.

PMID- 19100587
TI  - ?

PMID- 19100588
TI  - A conceptual framework for public health: NICE's emerging approach.
AB  - This paper outlines the National Institute for Health and Clinical Excellence's
      (NICE) emerging conceptual framework for public health. This is based on the
      experience of the first 3 years of producing public health guidance at NICE (2005
      2008). The framework has been used to shape the revisions to NICE's public health
      process and methods manuals for use post 2009, and will inform the public health
      guidance which NICE will produce from April 2009. The framework is based on the
      precept that both individual and population patterns of disease have causal
      mechanisms. These are analytically separate. Explanations of individual diseases
      involve the interaction between biological, social and related phenomena.
      Explanations of population patterns involve the same interactions, but also
      additional interactions between a range of other phenomena working in tandem.
      These are described. The causal pathways therefore involve the social, economic
      and political determinants of health, as well as psychological and biological
      factors. Four vectors of causation are identified: population, environmental,
      organizational and social. The interaction between the vectors and human
      behaviour are outlined. The bridge between the wider determinants and individual
      health outcomes is integration of the life course and the lifeworld.

PMID- 19100589
TI  - Does the public health mindset want to change?

PMID- 19100591
TI  - A performance analysis of echographic ultrasonic techniques for non-invasive
      temperature estimation in hyperthermia range using phantoms with scatterers.
AB  - Optimization of efficiency in hyperthermia requires a precise and non-invasive
      estimation of internal distribution of temperature. Although there are several
      research trends for ultrasonic temperature estimation, efficient equipments for
      its use in the clinical practice are not still available. The main objective of
      this work was to research about the limitations and potential improvements of
      previously reported signal processing options in order to identify research
      efforts to facilitate their future clinical use as a thermal estimator. In this
      document, we have a critical analysis of potential performance of previous
      ultrasonic research trends for temperature estimation inside materials, using
      different processing techniques proposed in frequency, time and phase domains. It
      was carried out in phantom with scatterers, assessing at their specific
      applicability, linearity and limitations in hyperthermia range. Three
      complementary evaluation indexes: technique robustness, Mat-lab processing time
      and temperature resolution, with specific application protocols, were defined and
      employed for a comparative quantification of the behavior of the techniques. The
      average increment per degrees C and mm was identified for each technique (3 KHz/
      degrees C in the frequency analysis, 0.02 rad/ degrees C in the phase domain,
      while increments in the time domain of only 1.6 ns/ degrees C were found). Their
      linearity with temperature rising was measured using linear and quadratic
      regressions and they were correlated with the obtained data. New improvements in
      time and frequency signal processing in order to reveal the potential thermal and
      spatial resolutions of these techniques are proposed and their subsequent
      improved estimation results are shown for simulated and measured A-scans
      registers. As an example of these processing novelties, an excellent potential
      resolution of 0.12 degrees C into hyperthermia range, with near-to-linear
      frequency dependence, could be achieved. Specifically defined "numerical" and
      physical multi-scatter phantoms are described, which mimic ultrasound velocity in
      tissues of about 1560 m/s @ 35 degrees C and have a quasi-uniform internal
      scattering structure designed to assure standard signal patterns adequate for
      processing comparisons in the same time and sound velocity conditions for all the
      techniques analyzed, and to obtain easily repeatable multi-pulse echo-patterns. A
      perfect lineal dependence (100% of correlation coefficient) between the unitary
      average increment measured by each technique and temperature rising was observed
      while working with simulated A-scan registers, where all the parameters are under
      an accurate control. Nevertheless a very small quadratic tendency appeared in the
      results obtained from experimental echo registers, which are more similar to a
      real tissues case. It would be an interesting future work to analyze the behavior
      of these techniques in real tissues in order to confirm or reject this light
      quadratic tendency. Finally, new methods were detailed and applied in order to
      precisely quantify the advantages of each estimation technique; their respective
      intrinsic limitations were also underlined.

PMID- 19100590
TI  - The eye in cerebral malaria: what can it teach us?
AB  - The pathophysiology of coma in cerebral malaria (CM) is not well understood.
      Obstruction of microcirculatory flow is thought to play a central role, but other
      hypotheses include roles for parasite- and host-derived factors such as immune
      mediators, and for increased blood-brain barrier permeability leading to raised
      intracranial pressure. The retinal vasculature is a direct extension of the
      cerebral vasculature. It is the only vascular bed easily accessible for
      visualisation and provides a unique opportunity to observe vascular pathology and
      its effect on neurological tissue. A specific retinopathy has been well described
      in African children with CM and its severity correlates with outcome. This
      retinopathy has been less well described in adults. The central mechanism causing
      malarial retinopathy appears to be microvascular obstruction, which has been
      demonstrated in affected retinas by fluorescein angiography. The presence in a
      central nervous system tissue of microvascular obstruction strongly supports the
      hypothesis that the sequestration of erythrocytes in small blood vessels and
      consequent obstruction of microcirculatory flow is an important mechanism causing
      coma and death in CM. Despite advances in the antimalarial treatment of severe
      malaria, its mortality remains approximately 15-20%. Adjunctive treatment
      targeting sequestration is a promising strategy to further lower mortality.

PMID- 19100592
TI  - Pleocytosis is associated with disruption of HIV compartmentalization between
      blood and cerebral spinal fluid viral populations.
AB  - INTRODUCTION: We hypothesized that pleocytosis, which is a marker of central
      nervous system (CNS) inflammation, would result in viral genetic equilibration or
      de-compartmentalization between HIV populations in the blood and cerebrospinal
      fluid (CSF), suggesting viral trafficking. METHODS: Study subjects, who started
      or interrupted their antiretroviral treatment, had viral loads measured and
      clonal viral env sequences generated from HIV RNA extracted from paired blood and
      CSF samples. White blood counts in CSF were also measured at each timepoint.
      Degree of inter-compartment segregation was calculated by posterior probability
      using linear discriminant analysis and multidimensional scaling. Co-receptor
      usage was determined using a trained support vector machine. RESULTS: Pleocytosis
      was strongly associated with disruption of viral compartmentalization.
      CONCLUSIONS: Inflammation in the CNS, marked by pleocytosis, allows HIV
      populations to mix between blood and CSF, which may increase the overall viral
      genetic diversity within the CSF.

PMID- 19100593
TI  - Mousepox in the C57BL/6 strain provides an improved model for evaluating anti
      poxvirus therapies.
AB  - The intranasal lethal mousepox model employing the A/Ncr mouse strain is used to
      evaluate anti-orthopoxvirus therapies. These infections mimic large droplet
      transmission and result in 100% mortality within 7-10 days with as little as 1
      PFU of ectromelia virus. Unlike the A/Ncr model, humans are less susceptible to
      lethal respiratory infections with variola virus and monkeypox virus as
      demonstrated by their lower mortality rates. In this study we show that a low
      dose intranasal infection of C57BL/6 mice results in 60-80% mortality and better
      models smallpox. Comparing CMX001 (HDP-cidofovir) efficacy in the A/Ncr strain
      and the C57BL/6 strain revealed that delayed treatment with CMX001 is more
      efficacious at preventing severe disease in the C57BL/6 strain. The increased
      efficacy of CMX001 in C57BL/6 over A/Ncr following an intranasal infection with
      ectromelia appears to be mediated by a stronger Th1 cell mediated response.
      Following footpad infection we show that the C57BL/6 strain has earlier and more
      robust transcriptional activity, Th1 cytokine secretions, antigen presenting
      activity and IFNgamma splenic CD8+ T cell responses as compared to the A/Ncr
      strain. As a result of the enhanced immune response in the C57BL/6 strain, non
      lethal intradermal ectromelia infections can therapeutically protect up to 3 days
      following a homologous, lethal intranasal infection - much like how smallpox
      vaccination can protect humans for up to 4 days following intranasal variola
      infection.

PMID- 19100594
TI  - Differential HIV-1 integration targets more actively transcribed host genes in
      neonatal than adult blood mononuclear cells.
AB  - We have recently shown an increased HIV-1 replication and gene expression in
      neonatal (cord) blood mononuclear cells compared with adult cells, which could be
      due to HIV-1 integration as it targets active host genes. Here we have
      characterized 468 HIV-1 integration sites within cord and adult blood T
      lymphocytes and monocyte-derived macrophages (MDM) from five donors. Several
      functional classes of genes were identified by gene ontology to be over
      represented, including genes for cellular components, maintenance of
      intracellular environment, enzyme regulation, cellular metabolism, catalytic
      activity and cation transport. Numerous potential transcription factor binding
      sites at the sites of integration were identified. Furthermore, the genes at the
      site of integration, transcription factors which potentially bind upstream of the
      HIV-1 promoter and factors that assist HIV-1 integration were found to be
      expressed at higher levels in cord than adult cells. Taken together, these
      results suggest HIV-1 integration occurred in a more actively transcribed genes
      in neonatal cells compared with adult cells, which may help explain a higher
      level of HIV-1 gene expression and replication in neonatal compared with adult
      cells.

PMID- 19100595
TI  - Impacts of membrane flux enhancers on activated sludge respiration and nutrient
      removal in MBRs.
AB  - This paper presents the findings of experimental investigations regarding the
      influence of 13 different flux enhancing chemicals (FeCl3, polyaluminium
      chloride, 2 chitosans, 5 synthetic polymers, 2 starches and 2 activated carbons)
      on respirometric characteristics and nitrification/denitrification performance of
      membrane bioreactor (MBR) mixed liquor. Flux enhancing chemicals are a promising
      method to reduce the detrimental effects of fouling phenomena via the
      modification of mixed liquor characteristics. However, potentially inhibiting
      effects of these chemicals on mixed liquor biological activity triggered the
      biokinetic studies (in jar tests) conducted in this work. The tested
      polyaluminium chloride (PACl) strongly impacted on nitrification (-16%) and
      denitrification rate (-43%). The biodegradable nature of chitosan was striking in
      endogenous and exogenous tests. Considering the relatively high costs of this
      chemical, an application for wastewater treatment does thus not seem to be
      advisable. Also, addition of one of the tested activated carbons strongly
      impacted on the oxygen uptake rate (-28%), nitrification (-90%) and
      denitrification rate (-43%), due to a decrease of pH. Results show that the
      changes in kLa values were mostly not significant, however, a decrease of 13% in
      oxygen transfer was found for sludge treated with PACl.

PMID- 19100596
TI  - Graphing evolutionary pattern and process: a history of techniques in archaeology
      and paleobiology.
AB  - Graphs displaying evolutionary patterns are common in paleontology and in United
      States archaeology. Both disciplines subscribed to a transformational theory of
      evolution and graphed evolution as a sequence of archetypes in the late
      nineteenth and early twentieth centuries. U.S. archaeologists in the second
      decade of the twentieth century, and paleontologists shortly thereafter,
      developed distinct graphic styles that reflected the Darwinian variational model
      of evolution. Paleobiologists adopted the view of a species as a set of
      phenotypically variant individuals and graphed those variations either as central
      tendencies or as histograms of frequencies of variants. Archaeologists presumed
      their artifact types reflected cultural norms of prehistoric artisans and the
      frequency of specimens in each type reflected human choice and type popularity.
      They graphed cultural evolution as shifts in frequencies of specimens
      representing each of several artifact types. Confusion of pattern and process is
      exemplified by a paleobiologist misinterpreting the process illustrated by an
      archaeological graph, and an archaeologist misinterpreting the process
      illustrated by a paleobiological graph. Each style of graph displays particular
      evolutionary patterns and implies particular evolutionary processes. Graphs of a
      multistratum collection of prehistoric mammal remains and a multistratum
      collection of artifacts demonstrate that many graph styles can be used for both
      kinds of collections.

PMID- 19100598
TI  - Laparoscopic radical prostatectomy in clinical T1a and T1b prostate cancer:
      oncologic and functional outcomes--a matched-pair analysis.
AB  - OBJECTIVES: To evaluate the effect of previous transurethral resection of the
      prostate (TURP) on surgical, functional, and oncologic outcomes after
      laparoscopic radical prostatectomy. METHODS: From a series of 2100 patients
      undergoing laparoscopic radical prostatectomy, we compared the intraoperative
      complications and functional and oncologic outcomes for 55 patients who had been
      diagnosed with prostate carcinoma on previous TURP (group 1), with those of 55
      matched patients who had not undergone previous prostate surgery (group 2). The
      patients were match-paired for age, operating surgeon, procedure type (eg, nerve
      sparing, lymph node dissection), anastamotic technique, pathologic stage, and
      Gleason score. The minimal duration of follow-up was 24 months. RESULTS: Both
      groups were similar with respect to patient age and pathologic stage. Of those
      with Stage cT1a and cT1b, 83.6% had a clinically significant tumor, with a mean
      tumor volume of 1.7 cm(3) for those with Stage cT1a and 2.4 cm(3) for those with
      Stage cT1b. The positive surgical margin rate was 14.5% and 16.3% for groups 1
      and 2, respectively. Biochemical recurrence developed in 12.7% and 11% of
      patients in groups 1 and 2, respectively. Neither outcome was significantly
      different between the 2 groups. The long-term continence rates were similar;
      however, previous TURP was associated with a lower continence rate (49.1%) at 3
      months compared with 61.8% for group 2 (P = .01). A nerve-sparing technique was
      used in 54% of group 1 patients. No significant difference was found in the
      potency rates between the 2 groups at 12 months. CONCLUSIONS: Laparoscopic
      radical prostatectomy after TURP is a challenging, but oncologically safe,
      procedure. The interval to total continence was delayed, but the potency rates
      remain unchanged.

PMID- 19100597
TI  - Single-dose and chronic corticosterone treatment alters c-Fos or FosB
      immunoreactivity in the rat cerebral cortex.
AB  - The aim of this study was to examine the effects of single-dose and chronic
      corticosterone treatment on the inducible transcription factor c-Fos and FosB,
      and thereby to estimate the effects of high-doses of corticosterone on calcium
      dependent neuronal responses in the rat cerebral cortex. At the same time we
      investigated the distribution of interneurons containing calretinin (CR),
      vasoactive intestinal polypeptide (VIP) and neuropeptide Y (NPY) in chronically
      treated animals in order to collect data on the involvement of inhibitory neurons
      in this process. Adult male rats were injected subcutaneously with 10mg
      corticosterone, whereas controls received the vehicle (sesame oil). The animals
      were fixed by transcardial perfusion 12 and 24h following single corticosterone
      injection, and the brains were processed for c-Fos and FosB immunohistochemistry.
      To investigate the effects of repeated corticosterone administration, rats were
      daily treated with the same amount of corticosterone (10mg/animal,
      subcutaneously) for 21 days. Controls were injected with vehicle. At the end of
      the experiment, the rats were perfused and immunohistochemistry was used to
      detect the presence of the FosB protein, CR, VIP and NPY. Quantitative evaluation
      of immunolabelled cells was performed in the neocortex and the hippocampus. The
      number of immunoreactive nuclei per unit area was used as a quantitative measure
      of the effects of corticosterone. It was found that a single-dose administration
      of corticosterone resulted in a significant, time-dependent increase of c-Fos
      protein immunoreactivity in the granule cell layer of the dentate gyrus, as well
      as in regions CA1 and CA3 of the hippocampus 12 and 24h post-injection with
      respect to control animals. Significant enhancement of c-Fos immunoreactivity was
      also observed in the neocortex at 12 and 24h post-injection. Single-dose
      treatment did not significantly alter FosB immunolabelling. Repeated
      administration of corticosterone produced a complex pattern of changes in FosB
      immunolabelling: significant increase in FosB immunoreactivity was detected in
      the granule cell layer of the dentate gyrus, with no significant changes in the
      CA1 and CA3 layers of the hippocampus and in the neocortex. However, a
      significant decrease of FosB induction in the neocortex was observed in
      chronically treated rats in comparison to single-dose injected animals (12h
      before immunohistochemistry). Analysis of immunohistochemical detection of
      interneuronal markers revealed a significant reduction of the CR immunolabelling
      in the CA3 area of the hippocampus. No changes in VIP or NPY immunoreactivity
      were found in the Ammon's horn 3 weeks following daily corticosterone treatment.
      NPY immunoreactivity was significantly attenuated in the neocortex. The present
      data suggest that single-dose corticosterone treatment increases immunoreactivity
      of c-Fos protein in a time-dependent manner, 12 and 24h post-injection in the rat
      hippocampus and the neocortex, whereas chronic corticosterone treatment
      influences FosB immunoreactivity, primarily in the dentate gyrus. Chronic
      corticosterone administration seems to affect CR levels in the CA3 area of the
      hippocampus.

PMID- 19100599
TI  - Operative versus nonoperative management of ureteropelvic junction obstruction in
      children.
AB  - OBJECTIVES: To describe and validate our strategy for treating patients with
      ureteropelvic junction obstruction operatively or nonoperatively according to
      ultrasonography and nuclear renal scan findings. METHODS: A retrospective
      analysis of 243 patients from 1999 to 2006 with grade 3-4 hydronephrosis was
      performed. Depending on the grade of hydronephrosis with parenchymal thinning on
      ultrasonography and renal function on the nuclear renal scan, patients were
      treated with immediate pyeloplasty, pyeloplasty after a period of observation, or
      observation only. RESULTS: Of 243 patients, 116 were found to have UPJO as
      determined by a half-life >20 minutes. The mean follow-up was 24.0 months (range
      3-69). Immediate pyeloplasty was performed in 32 children, and 84 were treated
      conservatively. Crossover from observation to surgery occurred in 47 children. In
      the immediate pyeloplasty group, the mean pre- and postoperative differential
      function was 30.4% and 38.8%, respectively (P < .0001). In the observation-only
      group (n = 37), the initial mean renal function was 41.4% and stayed stable
      throughout the follow-up period, at a mean of 43.2% (P = .2764). In the delayed
      pyeloplasty group (n = 47), the initial mean renal function was 35.9% and
      increased to a mean of 41.6% after intervention (P = .0003). The median
      improvement of hydronephrosis on ultrasonography for those who underwent
      immediate surgery from before to after the intervention was from grade 4 to grade
      3 (P < .0001). For those not undergoing surgery, it improved from grade 4 to
      grade 2.25 (P = .0026) and for those who underwent delayed surgery, from grade 4
      to 3 (P = .0003). CONCLUSIONS: According to our findings, the serial
      ultrasonography findings and initial renal function on nuclear renal scan are
      better indicators than the half-life alone for determining whether pyeloplasty is
      indicated.

PMID- 19100600
TI  - Phase I-II RTOG study (99-06) of patients with muscle-invasive bladder cancer
      undergoing transurethral surgery, paclitaxel, cisplatin, and twice-daily
      radiotherapy followed by selective bladder preservation or radical cystectomy and
      adjuvant chemotherapy.
AB  - OBJECTIVES: To evaluate the safety, tolerance, protocol completion rate, tumor
      response rate, and patient survival of chemoradiotherapy for patients with muscle
      invasive operable bladder cancer. METHODS: After transurethral resection of the
      tumor in patients with Stage T2-T4a bladder cancer, twice-daily radiotherapy with
      paclitaxel and cisplatin chemotherapy induction (TCI) was administered. If repeat
      biopsy showed less than Stage T1 disease, consolidation with TCI was given. If
      repeat biopsy showed greater than Stage T1 disease, cystectomy was recommended.
      Adjuvant gemcitabine and cisplatin were given to all patients. RESULTS: A total
      of 80 patients met protocol eligibility. TCI resulted in 26% developing grade 3-4
      acute toxicity, mainly gastrointestinal (25%). During consolidation TCI, grade 3
      4 acute toxicity, all transient, was reported in 8%. Four cycles of adjuvant
      chemotherapy were completed per protocol or with minor deviations in 70% of the
      patients. Adjuvant treatment was associated with grade 3 toxicity in 46% and
      grade 4 in 26%. One patient had a fatal hemorrhagic stroke. Late bladder
      radiation toxicity was evaluated in 53 patients with > or = 2 years of follow-up.
      Of these 53 patients, 3 experienced self-limited, late grade 3 bladder toxicity.
      The postinduction complete response rate was 81% (65/80), 36 of the 80 patients
      died (22 of bladder cancer). At a median follow-up of 49.4 months, the actuarial
      5-year overall and disease-specific survival rate was 56% and 71%, respectively.
      CONCLUSIONS: These favorable tumor response rates with possible increased bladder
      preservation rates suggest that this treatment regimen deserves further study.

PMID- 19100601
TI  - Effectiveness of three-dimensional fluoroscopy in percutaneous nephrostomy: an
      animal model study.
AB  - OBJECTIVES: To present, in an experimental study, an assessment of innovative
      digital fluoroscopy systems with three-dimensional (3D) reconstruction for use in
      endourologic applications. METHODS: The experiment was performed in a pig model.
      We used 5 pigs. An obstructive uropathy model was created in the right kidney to
      dilate the urinary tract for group 1. Group 2 consisted of the nondilated left
      kidney. After selecting the tract on the 3D image, the lower caliceal group was
      punctured in the 2 kidneys under fluoroscopic control, to assess the efficiency
      of the 3D reconstruction when selecting the renal calix to be punctured. RESULTS:
      The 3D reconstruction system allowed us to obtain reconstruct the pelvis in three
      dimensions, isolated as the pelvis and renal parenchyma, as well as the adjacent
      bony relationships. In this study, the success rate was 100% for locating the
      selected renal calix. CONCLUSIONS: With this 3D reconstruction system, we were
      able to obtain a series of images that allowed for the study of the volume of the
      kidney, perfectly determining its renal calix distribution in the operating room.
      This enabled us to determine the precise delineation of the target calix. We,
      therefore, consider this new urologic application of fluoroscopy very useful in
      surgical planning for antegrade access of the upper urinary tract.

PMID- 19100602
TI  - Testicular microlithiasis preceding metastatic mixed germ cell tumor--first
      pediatric report and recommended management of testicular microlithiasis in the
      pediatric population.
AB  - Testicular microlithiasis is a condition that has been associated with testis
      cancer in men and boys. We report the case of a 16-year-old boy who developed
      metastatic mixed germ cell testicular tumor in the setting of testicular
      microlithiasis detected by previous ultrasonography. The tumor developed in
      between semiannual visits and was detected by self-examination. Chest imaging
      revealed 2 lung lesions, and the beta-human chorionic gonadotropin level was
      elevated at presentation. Because of the particular nature of healthcare
      surveillance in the pediatric population, we recommend annual surveillance of
      boys with testicular microlithiasis, including physical examination, repeated
      instruction regarding self-examination, and ultrasonography.

PMID- 19100603
TI  - Chronic periglandular inflammation on prostate needle biopsy does not increase
      the likelihood of cancer on subsequent biopsy.
AB  - PURPOSE: Recent literature suggests a role for chronic inflammation in the
      development of prostate cancer. We investigated the association of chronic
      periglandular inflammation on prostate needle biopsy with subsequent prostate
      cancer development and clinical disease features at presentation. METHODS: Six
      hundred fifty-five patients were abstracted from a prostate/needle biopsy
      registry from Brigham and Women's Hospital presenting with prostate-specific
      antigen (PSA) > 4 ng/mL or abnormal digital rectal examination (DRE) between the
      years 1990 and 2004. DRE, PSA, PSA density, prostate volume, histology, and age
      were analyzed to identify clinical and pathologic associations with inflammation.
      Chronic inflammation was defined as an inflammatory cell infiltrate composed
      predominately of lymphocytes in a periglandular distribution. A subset of
      patients (n = 308) with follow-up biopsy results were used to identify if
      prostate inflammation predicted development of prostate cancer. RESULTS: Modeling
      performed based on 4 biopsy samples revealed prostate volume (P < .001) and DRE
      (P = .02) as significant predictors of inflammation; DRE lost significance in
      models accounting for volume. Kaplan-Meier analysis demonstrated inflammation
      does not predict subsequent prostate cancer (P = .2). Cox models with the same
      endpoint show inflammation at initial biopsy (P = .3), inflammation at last
      biopsy (P = .4), and inflammation on any previous biopsy (P = .08) are not
      associated with time-to-positive biopsy. CONCLUSIONS: Although inflammation on
      initial and subsequent biopsy does not predict prostate cancer in this cohort, we
      cannot dismiss its role in prostate cancer pathogenesis. Additional research is
      necessary to explore the relationship between prostate inflammation and prostate
      cancer development.

PMID- 19100604
TI  - Long-term results of penile disassembly technique for correction of epispadias.
AB  - OBJECTIVES: To present our long-term results with complete penile disassembly for
      epispadias repair. METHODS: We performed a retrospective review of our surgical
      records from 1996 to 2008. Group 1 included 12 patients who had undergone
      complete penile disassembly as a part of complete primary repair of bladder
      exstrophy, and group 2 included 9 patients with isolated epispadias. RESULTS: The
      mean follow-up after epispadias repair was 58.2 and 58.6 months for groups 1 and
      2, respectively. At the last follow-up visit, 83.3% of group 1 and 100% of group
      2 were completely dry or had dry intervals >4 hours. Of the 21 children, 7
      (33.3%) experienced minor complications, 4 in group 1 and 3 in group 2. No
      ischemic changes of the glans penis or corporal bodies were observed in either
      group. Erectile function was preserved in all patients. CONCLUSIONS: Complete
      penile disassembly technique can achieve total or near complete urinary
      continence, decreasing the morbidity of multiple procedures and potentially
      allowing children to achieve continence at an earlier age. Our experience, with a
      mean follow-up of nearly 5 years and an overall complication rate of 33.3%, is
      comparable to that of other published series.

PMID- 19100605
TI  - Alpha-blocker plus diuretic combination therapy as second-line treatment for
      nocturia in men with LUTS: a pilot study.
AB  - OBJECTIVES: To determine the efficacy of a diuretic agent, hydrochlorothiazide,
      as second-line therapy after failed alpha-blocker therapy for men with nocturia.
      METHODS: The study inclusion criteria were a < 25% reduction in nocturia using
      the International Prostate Symptom Score question 7, a < 25% reduction in
      nocturia using the frequency-volume chart, and/or nocturia > or = 2/night
      (according to the frequency-volume chart) after 4 weeks of terazosin therapy. A
      total of 72 patients were entered into the study and treated with 25 mg of
      hydrochlorothiazide and 4 mg of terazosin once daily for 4 weeks. Of the 72
      eligible men, 53 completed the study. RESULTS: No serious side effects occurred
      among the treated patients. Using the International Prostate Symptom Score, a
      reduction of > or = 50%, 25%-49%, 0%-24% and an increase in nocturia was observed
      in 7, 7, 31, and 8 patients, respectively. Using the frequency-volume chart, 17
      patients reported reduced nocturia by more than one half, 5 reported a reduction
      of 25%-49%, and 31 reported no response to treatment or an increase in nocturia.
      At baseline, all except for 1 patient had nocturnal polyuria (nocturnal polyuria
      index > 33%), and, after the combination therapy, the nocturnal polyuria had
      resolved in 6 (11.5%) of the 52 patients with nocturnal polyuria at baseline.
      CONCLUSIONS: Hydrochlorothiazide combined with terazosin was safe and effective
      in reducing nocturnal frequency for some men after failed terazosin therapy. Our
      findings suggest that the use of a diuretic agent, such as hydrochlorothiazide,
      might be a reasonable second-line treatment option for these patients, especially
      for those with nocturnal polyuria.

PMID- 19100606
TI  - Selective postoperative imaging after ureteroscopy.
AB  - OBJECTIVES: To evaluate the need of routine follow-up imaging after ureteroscopy.
      METHODS: We performed a retrospective chart review of patients undergoing
      ureteroscopy for urolithiasis. Selective imaging was performed in the initial
      postoperative phase (1-3 weeks after removal of the ureteral stent) if the
      procedure was classified as complicated because of the presence of an impacted
      stone, the need for balloon dilation, intraoperative ureteral perforation, or
      postoperative pain after stent removal. Uncomplicated ureteroscopy was followed
      by repeat imaging if the patient developed recurrent renal colic or as
      surveillance for new stone growth at 6-12 months of follow-up. RESULTS: A total
      of 267 ureteroscopic procedures were performed on 253 patients. The data from 214
      of 253 patients (84.6%) who had undergone noncontrast-enhanced computed
      tomography imaging > or = 1 month after surgery were analyzed. The mean follow-up
      was 14.5 months (range 1-66). The incidence of stricture was 1.4% (3/214). The
      incidence in the selective imaging (complicated ureteroscopy) group was 5.3%
      (3/56). In uncomplicated ureteroscopy group, it was 0% (0/158). Ureteral
      stricture developed in 3 of 11 patients with stone impaction (27.2%, P = .002), 2
      of 14 patients undergoing ureteral balloon dilation (10.4%, P = .0052), and in 1
      of 6 patients with an intraoperative mucosal perforation (16.6%, P = .0326).
      Persistent postoperative pain after stent removal was not predictive of stricture
      formation (3.6%, P = .139). CONCLUSIONS: The results of our study have shown that
      selective imaging as determined by the intraoperative findings of complicated
      ureteroscopy (eg, impacted stone, balloon dilation, mucosal perforation) will
      detect postoperative ureteral strictures. Routine follow-up imaging is not
      essential after uncomplicated ureteroscopy.

PMID- 19100607
TI  - Does race affect postoperative outcomes in patients with low-risk prostate cancer
      who undergo radical prostatectomy?
AB  - OBJECTIVES: To assess the magnitude of racial disparities in prostate cancer
      outcomes following radical prostatectomy for low-risk prostate cancer. METHODS:
      We retrospectively reviewed our database of 2407 patients who under went radical
      prostatectomy and isolated 2 cohorts of patients with low-risk prostate cancer.
      Cohort 1 was defined using liberal criteria, and cohort 2 was isolated using more
      stringent criteria. We then studied pre- and postoperative parameters to discern
      any racial differences in these 2 groups. Statistical analyses, including log
      rank, chi(2), and Fisher's exact analyses, were used to ascertain the
      significance of such differences. RESULTS: Preoperatively, no significant
      differences were found between the white and African-American patients with
      regard to age at diagnosis, mean prostate-specific antigen, median follow-up, or
      percentage of involved cores on prostate biopsy. African-American patients in
      cohort 1 had a greater mean body mass index than did white patients (26.9 vs
      27.8, P = .026). The analysis of postoperative data demonstrated no significant
      difference between white and African-American patients in the risk of biochemical
      failure, extraprostatic extension, seminal vesicle involvement, positive surgical
      margins, tumor volume, or risk of disease upgrading. African-American patients in
      cohort 2 demonstrated greater all-cause mortality compared with their white
      counterparts (9.4% vs 3.1%, P = .027). CONCLUSIONS: In patients with low-risk
      prostate cancer treated with radical prostatectomy, there exist no significant
      differences in surrogate measures of disease control, risk of disease upgrading,
      estimated tumor volume, or recurrence-free survival between whites and African
      Americans.

PMID- 19100608
TI  - Cost effectiveness of a test to detect metastases for endometrial cancer.
AB  - OBJECTIVE: To estimate the potential cost-effectiveness of a hypothetical test to
      screen for lymph node metastases in women with newly diagnosed, apparent early
      stage endometrial cancer. METHODS: A decision model was constructed to inform a
      choice between the following strategies: (1) Usual care, in which the probability
      of undergoing full surgical staging (29%) is based on literature review; (2) Non
      invasive diagnostic testing for metastasis (Testing), in which patients with
      abnormal test results undergo full surgical staging; (3) 100% referral, in which
      all patients are referred for full surgical staging. Survival was modeled using
      Surveillance Epidemiology and End Results (SEER) database. Base case diagnostic
      test characteristic estimates (sensitivity 0.90, specificity 0.90) were varied
      for sensitivity analysis. Cost of the diagnostic test was set at $500 and varied;
      costs of treatment for endometrial cancer (surgery, adjuvant therapies, diagnosis
      of recurrence, salvage therapies and palliative care) were incorporated. RESULTS:
      Usual care was the least expensive strategy, while Testing was more expensive and
      more effective, with an incremental cost-effectiveness ratio (ICER) of $18,785
      per year of life saved (YLS) compared to Usual care. 100% referral was the most
      expensive and most effective strategy, with an ICER of $35,358 per YLS compared
      to Testing. Results are relatively sensitive to variation in test characteristics
      and the cost of the diagnostic test but insensitive to cost of treatment and
      probability of adjuvant therapies. Testing remains cost-effective compared to
      Usual care unless the usual rate of referral to a Gynecologic Oncologist for full
      staging exceeds 90%. CONCLUSIONS: Given the current low rates of full surgical
      staging and/or referral to a Gynecologic Oncologist, a diagnostic test to detect
      nodal metastasis for endometrial cancer has potential to be cost-effective when
      compared to usual care. Testing is also potentially cost-effective compared to
      100% referral at very high test sensitivities and at the lower range of test
      costs.

PMID- 19100609
TI  - Follicle and oocyte morphology in ewes after treatment with insulin in the late
      follicular phase.
AB  - Stress reduces fertility in ruminants. Various experimental models, such as
      insulin-induced hypoglycaemia, have been used to investigate the mechanisms
      involved, and have revealed abnormal LH profiles (both pulse and surge
      secretion). This disruption affects follicular function and it is proposed there
      may be negative consequences on subsequent oocyte morphology. Insulin (5iu/kg),
      administered to ewes in the late follicular phase, induced hypoglycemia for 10h,
      decreased estradiol concentrations for 8-12h and delayed the LH surge by 15h.
      Although the diameters of dominant follicles just before ovulation were not
      affected, granulosa cells had fewer pycnotic nuclei, less apoptosis and increased
      proliferation 16-17h after the LH surge. Nevertheless, we did not observe gross
      ultra-structural differences in nuclear, cytoplasmic or cumulus maturity between
      oocytes from insulin-treated and control animals. This suggests that reduced LH
      pulsatility and a delay in the LH surge may only produce very subtle changes in
      gross oocyte morphology, imperceptible by electron microscopy.

PMID- 19100610
TI  - Pregnancy patterns during the early fetal period in high producing dairy cows
      treated with GnRH or progesterone.
AB  - In order to explore pregnancy patterns in high producing dairy cows treated with
      GnRH or progesterone at pregnancy diagnosis (Days 28-34), two consecutive
      experiments were designed. In Experiment 1, cows bearing a single embryo were
      randomly assigned to a PRID (n=40; cows fitted with a progesterone releasing
      intra-vaginal device for 28 days), GnRH (n=40; cows receiving GnRH) or Control
      (n=26; untreated cows) group. PRID treatment led to a rise in plasma progesterone
      concentrations in the 7 days following the onset of treatment compared to the
      other two groups. In Experiment 2, in which we also examined twin pregnancies,
      animals were randomly assigned to PRID (n=312) or GnRH (n=294) treatment groups.
      Treatments were the same as described for Experiment 1. Logistic regression
      procedures revealed that in cows with a single corpus luteum, the probability of
      pregnancy loss between the first (Days 28-34) and second (Days 65-62) pregnancy
      diagnosis decreased by a factor of 0.51 in the PRID group compared to the GnRH
      group. However, in cows with two or more corpora lutea, PRID treatment increased
      the likelihood of pregnancy loss by a factor of three, compared to GnRH
      treatment. In cows carrying twins, the conceptus reduction rate was higher
      (P=0.02) for the GnRH (36%) than for the PRID (16.4%) group. Formation of a new
      corpus luteum was recorded in 17.7% of cows in the GnRH group. Our results
      indicate that compared to GnRH treatment, progesterone treatment given at
      pregnancy diagnosis in high producing dairy cows, reduced by a factor of 0.51 and
      increased by a factor of 3 the probability of pregnancy loss in cows with a
      single or with two or more corpora lutea, respectively, and reduced the conceptus
      reduction rate in cows carrying twins. The practical implications of our findings
      are that in herds with a high incidence of early fetal loss of a non-infectious
      nature, treatment at the time of pregnancy diagnosis with PRID in cows with one
      corpus luteum and with GnRH in cows with two or more corpora lutea should offer
      considerable benefits.

PMID- 19100611
TI  - Self-adhesive resin cement versus zinc phosphate luting material: a prospective
      clinical trial begun 2003.
AB  - OBJECTIVES: The literature demonstrates that conventional luting of metal-based
      restorations using zinc phosphate cements is clinically successful over 20 years.
      This study compared the clinical outcomes of metal-based fixed partial dentures
      luted conventionally with zinc phosphate and self-adhesive resin cement. METHODS:
      Forty-nine patients (mean age 54+/-13 years) received 49 metal-based fixed
      partial dentures randomly luted using zinc phosphate (Richter & Hoffmann, Berlin,
      Germany) or self-adhesive resin cement (RelyX Unicem Aplicap, 3M ESPE, Germany)
      at the University Medical Center Regensburg. The core build-up material was
      highly viscous glass ionomer; the finishing line was in dentin. The study
      included 42 posterior, 5 anterior crowns and two onlays. Forty-seven restorations
      were made of precious alloys, 2 of non-precious alloys. The restorations were
      clinically examined every year. The clinical performance was checked for plaque
      (0-5; PI, Quigley-Hein), bleeding (0-4; PBI; Muhlemann) and attachment scores.
      The examination included pulp vitality and percussion tests. STATISTICS: Means of
      scores, standard deviation, cumulative survival and complication rates were
      calculated using life tables. RESULTS: The mean observation time was 3.16+/-0.6
      years (min: 2.0; max: 4.5 years). During that time no restoration was lost, no
      recementation became necessary. One endodontic treatment was performed in the
      self-adhesive composite group after 2.9 years. At study end bleeding (1.44 RelyX
      Unicem vs. 1.25 zinc phosphate) and plaque (1.64 RelyX Unicem vs. 1.0 zinc
      phosphate) scores showed no statistically significant difference. SIGNIFICANCE:
      The self-adhesive resin cement performed clinically as well and can be used as
      easily as zinc phosphate cement to retain metal-based restorations over a 38
      month observation period.

PMID- 19100612
TI  - Ion release characteristics, precipitate formation and sealing ability of a
      phosphate glass-polycaprolactone-based composite for use as a root canal
      obturation material.
AB  - OBJECTIVES: The filling material used to obturate root canal systems during the
      common dental procedure, root canal treatment, has popularly involved gutta
      percha (GP) in one of its many forms for almost a 100 years. An optimal root
      filling material should provide a predictable seal, inhibit or kill residual
      bacteria, prevent re-contamination and facilitate periapical healing. Although
      the goal of obturation is stated as the creation of a "seal", its precise role
      still remains elusive and the seal offered suspect. The primary goal of the study
      was to develop a novel polycaprolactone/phosphate glass composite deliverable as
      a root filling and capable of releasing ionic species to enable a predictable
      seal in an aqueous environment. MATERIALS AND METHODS: Different compositions of
      polycaprolactone-iron phosphate glass (Fe(2)O(3) 1, 3 and 5mol%) composites were
      produced and delivered into an ex vivo root canal model. Standardized root canals
      were prepared in extracted human teeth. The teeth were examined for root filling
      adaptation and precipitate formation (SEM), ion release (Na(+), Ca(2+), PO(4)(3
      ), P(2)O(7)(4-), P(3)O(9)(3-), and P(5)O(10)(5-)), and sealing ability. The
      experiments were controlled with teeth obturated with contemporary GP and a
      conventional zinc-oxide/eugenol sealer. RESULTS: Adaptation of the experimental
      material was statistically significantly better than the GP control groups.
      Precipitate formation was noted in some specimens but all released various ionic
      species in an inverse proportion to the iron oxide concentration. The
      experimental material exhibited significantly (P<0.001) less leakage after 7 days
      immersion in saline compared with those not immersed, or the control GP group.
      SIGNIFICANCE: PCL-phosphate glass composites showed good potential as a root
      filling material capable of producing a seal in an aqueous environment without a
      sealer.

PMID- 19100613
TI  - Calculation of contraction stresses in dental composites by analysis of crack
      propagation in the matrix surrounding a cavity.
AB  - OBJECTIVES: Polymerization contraction of dental composite produces a stress
      field in the bonded surrounding substrate that may be capable of propagating
      cracks from pre-existing flaws. The objectives of this study were to assess the
      extent of crack propagation from flaws in the surrounding ceramic substrate
      caused by composite contraction stresses, and to propose a method to calculate
      the contraction stress in the ceramic using indentation fracture. METHODS:
      Initial cracks were introduced with a Vickers indenter near a cylindrical hole
      drilled into a glass-ceramic simulating enamel. Lengths of the radial indentation
      cracks were measured. Three composites having different contraction stresses were
      cured within the hole using one- or two-step light-activation methods and the
      crack lengths were measured. The contraction stress in the ceramic was calculated
      from the crack length and the fracture toughness of the glass-ceramic.
      Interfacial gaps between the composite and the ceramic were expressed as the
      ratio of the gap length to the hole perimeter, as well as the maximum gap width.
      RESULTS: All groups revealed crack propagation and the formation of contraction
      gaps. The calculated contraction stresses ranged from 4.2 MPa to 7.0 MPa. There
      was no correlation between the stress values and the contraction gaps.
      SIGNIFICANCE: This method for calculating the stresses produced by composites is
      a relatively simple technique requiring a conventional hardness tester. The
      method can investigate two clinical phenomena that may occur during the placement
      of composite restorations, i.e. simulated enamel cracking near the margins and
      the formation of contraction gaps.

PMID- 19100614
TI  - Via zinc(II) protoporphyrin to the synthesis of poly(ZnPP-MAA-EGDMA) for the
      imprinting and selective binding of bilirubin.
AB  - Poly(zinc protoporphyrin-methacrylic acid-ethyl glycol dimethylacrylate)
      (poly(ZnPP-MAA-EGDMA)) imprinted with alpha-bilirubin can cause spectroscopic
      change in wavelength and absorption intensity due to the metal-ion coordination
      between ZnPP and bilirubin. The fluorescent imprinted polymer was able to
      selectively bind alpha-bilirubin. The corresponding imprinted polymer monolith
      was synthesized by using the functional monomer, methacrylic acid and the
      fluorescent monomer, zinc(II) protoporphyrin. Although the imprinted polymers
      (MIPs) using methacrylic acid, protoporphyrin, or zinc(II) protoporphyrin alone
      as the only functional monomer could bind bilirubin, the imprinting effects were
      all comparably inferior to the imprinted poly(ZnPP-MAA-EGDMA). Therefore, it
      revealed that via the combined utilization of ZnPP and MAA for the fluorescent
      and functional effect, the MIPs thus prepared were then able to create the highly
      selective cavities. The optimal condition for the heated polymerization of the
      imprinted poly(ZnPP-MAA-EGDMA) was found to be 60 degrees C for 6 h. The
      imprinting factor of 3.069 could be achieved from the fluorescent imprinted
      polymer by comparing the binding results obtained from the MIP and the NIP (non
      imprinted polymer). The imprinting factor obtained from bilirubin/biliverdin
      mixture solution was reduced to 2.111 because of the presence of biliverdin. The
      selectivity toward bilirubin of 2.269 from the bilirubin/biliverdin mixture was
      obtained. Therefore, to utilize ZnPP for the preparation of the imprinted
      materials confirmed the selective binding and detection of bilirubin via the
      fluorescent approach.

PMID- 19100615
TI  - Macromolecular diffusion and release from self-assembled beta-hairpin peptide
      hydrogels.
AB  - Self-assembling peptide hydrogels are used to directly encapsulate and
      controllably release model FITC-dextran macromolecules of varying size and
      hydrodynamic diameters. MAX1 and MAX8 are two peptide sequences with different
      charge states that have been designed to intramolecularly fold and self assemble
      into hydrogels at physiological buffer conditions (pH 7.4, 150 mM NaCl). When
      self-assembly is initiated in the presence of dextran or protein probes, these
      macromolecules are directly encapsulated in the gel. Self-diffusion studies using
      fluorescence recovery after photobleaching (FRAP) and bulk release studies
      indicate that macromolecule mobility within, and release out of, these gels can
      be modulated by varying the hydrogel mesh size. The average mesh size can be
      modulated by simply varying the concentration of a given peptide used to
      construct the gel or by altering the peptide sequence. In addition, results
      suggest that electrostatic interactions between the macromolecules and the
      peptide network influence mobility and release. Depending on probe size, release
      half-lives can be varied from 8h to over a month.

PMID- 19100616
TI  - Regulation of cellular morphology using temperature-responsive hydrogel for
      integrin-mediated mechanical force stimulation.
AB  - A new culture substrate was developed for cells to be equibiaxially stretched
      using fibronectin (Fn)-immobilized temperature-responsive hydrogel. The cells
      cultured on the gel substrate were equibiaxially stretched with swelling of the
      gel, which was accompanied by slight changes of temperature. During gel swelling,
      changes of cell shape were clearly observed by optical microscopy because of high
      transparency of the gel. ERK was highly and transiently activated by mechanical
      stimulation whereas focal adhesion kinase (FAK) was not, indicating that
      mechanical signals were transduced into biochemical signals in cells. We found
      that cells formed filopodia-like structures in response to mechanical cues,
      suggesting that mechanical forces facilitated actin polymerization at the
      peripheral region. In the cytoplasm, paxillin-containing fibrous structures were
      formed along actin fibers. These results indicate that we can perform both
      analysis of intracellular signal transduction and observation of cell shapes at
      high magnification in our method.

PMID- 19100617
TI  - Galactosylated fluorescent labeled micelles as a liver targeting drug carrier.
AB  - Galactosylated and fluorescein isothiocyanate (FITC) labeled polycaprolactone-g
      dextran (Gal-PCL-g-Dex-FITC) polymers were synthesized. The grafted polymers can
      self-assemble into stable micelles in aqueous medium and in serum. Transmission
      electron microscopy (TEM) images showed that the self-assembled micelles were
      regularly spherical in shape. Micelle size determined by size analysis was around
      120 nm. The anti-inflammation drug prednisone acetate as a model drug was loaded
      in the polymeric micelles, and the in vitro drug release was investigated. The
      galactosylated micelles could be selectively recognized by HepG2 cells and
      subsequently accumulate in HepG2 cells. The in vivo study demonstrated the
      relative uptake of the micelles by liver is much higher than the other tissues,
      indicating that the galactosylated micelles have great potential as a liver
      targeting drug carrier.

PMID- 19100618
TI  - The targeting of 14-succinate triptolide-lysozyme conjugate to proximal renal
      tubular epithelial cells.
AB  - We have synthesized a renal-specific drug carrier, 14-succinyl triptolide
      lysozyme (TPS-LZM) conjugate for targeted delivery of TP to the PTECs. TPS-LZM
      could be taken up by HK-2 cells, free TP would be degraded and released, mainly
      from basolateral side of the cells. Compared with TP, the overall targeting
      efficiency (TE) of TPS-LZM was significantly enhanced from 11.74% to 95.54% and
      its MRT was moderately prolonged from 3.08h to 4.10h. At very low concentration,
      TPS-LZM could significantly reverse the disease progression in renal ischemia
      reperfusion (I/R) injury animal models, while the mixture of free TP and LZM was
      ineffective. Further, TPS-LZM conjugate presented much lower hepatotoxicity (0.78
      folds lower than TP) and no adverse effect on the immune (1.13 folds higher than
      TP) and genital system. Thus, TPS-LZM represents a very effective drug candidate
      for specific treatment of immunological renal diseases with low adverse side
      effect.

PMID- 19100619
TI  - Effect of increasing maternal body mass index on oxidative and nitrative stress
      in the human placenta.
AB  - Maternal obesity is an increasing problem in obstetrics associated with adverse
      pregnancy outcomes and delivery complications. As an inflammatory state, where
      elevated levels of pro-inflammatory cytokines are found, obesity can lead to the
      increased incidence of oxidative and nitrative stress. These stresses may result
      in protein oxidation and protein nitration respectively, which are post-
      translational covalent modifications that can modify the structure and
      subsequently alter the function of a protein. The objective of this study was to
      examine whether placental oxidative and nitrative stress increase with increasing
      maternal body mass index. Placental tissue was collected from three groups of
      patients categorized as lean, overweight and obese. The presence of nitrotyrosine
      residues, a marker of nitrative stress, and antioxidant enzymes, as markers of
      oxidative stress, were assessed by immunohistochemistry, Western blot and ELISA.
      Protein carbonyl formation, a specific measure of protein oxidation, was measured
      by OxyBlot kit. Nitrotyrosine residues were increased in obese compared to lean
      and overweight groups although localization was unaltered across the three
      groups. Superoxide dismutase enzyme expression, localization and activity was
      unaltered between the groups. Protein carbonyl formation was greater in the lean
      compared to the overweight individuals. This study demonstrates that with
      increasing maternal body mass index there is an increase in placental nitrative
      stress. There does not appear to be a corresponding increase in oxidative stress
      and indeed we demonstrate some evidence of a decrease in oxidative effects in
      these placenta samples. Potentially the formation of peroxynitrite may be
      consuming reactive oxygen species and reducing oxidative stress. There may be a
      shift in the balance between nitrative and oxidative stress, which may be a
      protective mechanism for the placenta.

PMID- 19100620
TI  - Mitochondrial free [Ca2+] levels and the permeability transition.
AB  - Mitochondrial Ca(2+) activates many processes, from mitochondrial metabolism to
      opening of the permeability transition pore (PTP) and apoptosis. However, there
      is considerable controversy regarding the free mitochondrial [Ca(2+)]
      ([Ca(2+)](M)) levels that can be attained during cell activation or even in
      mitochondrial preparations. Studies using fluorescent dyes (rhod-2 or similar),
      have reported that phosphate precipitation precludes [Ca(2+)](M) from increasing
      above 2-3 microM. Instead, using low-Ca(2+)-affinity aequorin probes, we have
      measured [Ca(2+)](M) values more than two orders of magnitude higher. We confirm
      here these values by making a direct in situ calibration of mitochondrial
      aequorin, and we show that a prolonged increase in [Ca(2+)](M) to levels of 0.5
      1mM was actually observed at any phosphate concentration (0-10mM) during
      continuous perfusion of 3.5-100 microM Ca(2+)-buffers. In spite of this high and
      maintained (>10 min) [Ca(2+)](M), mitochondria retained functionality and the
      [Ca(2+)](M) drop induced by a protonophore was fully reversible. In addition,
      this high [Ca(2+)](M) did not induce PTP opening unless additional activators
      (phenyl arsine oxide, PAO) were present. PAO induced a rapid, concentration
      dependent and irreversible drop in [Ca(2+)](M). In conclusion [Ca(2+)](M) levels
      of 0.5-1mM can be reached and maintained for prolonged periods (>10 min) in
      phosphate-containing medium, and massive opening of PTP requires additional pore
      activators.

PMID- 19100622
TI  - Polybrominated diphenyl ether flame retardants in the U.S. marine environment: a
      review.
AB  - Polybrominated diphenyl ethers (PBDEs) are used as flame retardants in polymeric
      materials such as furnishing foam, rigid plastics and textiles. The U.S. has
      historically led the world production of these man-made chemicals and was
      responsible for about 50% of the total global demand in 2001. Paradoxically,
      scientific studies addressing sources, behavior and fate of PBDEs in the U.S.
      environment are limited when compared to those in Europe. This paper reviews the
      distribution of PBDEs in marine and estuarine matrices of the three U.S. coasts
      (Atlantic, Pacific and Gulf of Mexico) and Alaska. PBDEs are ubiquitous in all
      compartments including water, sediment and biota. Contamination is higher in
      urbanized regions such as the coast of California. In numerous cases,
      concentrations of PBDEs in U.S. marine matrices are among the highest in the
      world. Higher PBDE levels in the U.S. marine environment reflect that over 90% of
      the Penta-BDE global production has been utilized in the United States. BDEs 47,
      99 and 100 typically dominate the composition of PBDEs in most samples and
      exhibit high concentrations in several matrices. BDEs 17, 28, 33, 49, 153, 154
      and 155 are also of concern since they are known to be present in a minor
      proportion in the Penta-BDE products. BDEs 206, 207, 208 and 209 which occur in
      Deca-BDE products do not appear to accumulate in most marine organisms although
      they may be debrominated into more toxic congeners. There is still no regulation
      addressing PBDEs contamination in the U.S. aquatic environments. Thus, efforts to
      understand the cycling of PBDEs in the environment as well as toxic effects in
      organisms are needed to support the development of quality criteria. Some PBDE
      congeners fulfill the criteria to be recognized as persistent organic pollutants
      (POPs). The addition of PBDEs to the list of POPs established by the United
      Nations Stockholm Convention will be important in elevating environmental
      concerns regarding these chemicals to an appropriate level of awareness.

PMID- 19100621
TI  - 2-Aminoethoxydiphenyl-borate (2-APB) increases excitability in pyramidal neurons.
AB  - Calcium ions (Ca(2+)) released from inositol trisphosphate (IP(3))-sensitive
      intracellular stores may participate in both the transient and extended
      regulation of neuronal excitability in neocortical and hippocampal pyramidal
      neurons. IP(3) receptor (IP(3)R) antagonists represent an important tool for
      dissociating these consequences of IP(3) generation and IP(3)R-dependent internal
      Ca(2+) release from the effects of other, concurrently stimulated second
      messenger signaling cascades and Ca(2+) sources. In this study, we have described
      the actions of the IP(3)R and store-operated Ca(2+) channel antagonist, 2
      aminoethoxydiphenyl-borate (2-APB), on internal Ca(2+) release and plasma
      membrane excitability in neocortical and hippocampal pyramidal neurons.
      Specifically, we found that a dose of 2-APB (100 microM) sufficient for
      attenuating or blocking IP(3)-mediated internal Ca(2+) release also raised
      pyramidal neuron excitability. The 2-APB-dependent increase in excitability
      reversed upon washout and was characterized by an increase in input resistance, a
      decrease in the delay to action potential onset, an increase in the width of
      action potentials, a decrease in the magnitude of afterhyperpolarizations (AHPs),
      and an increase in the magnitude of post-spike afterdepolarizations (ADPs). From
      these observations, we conclude that 2-APB potently and reversibly increases
      neuronal excitability, likely via the inhibition of voltage- and Ca(2+)-dependent
      potassium (K(+)) conductances.

PMID- 19100623
TI  - IL-12 p40 homodimer, but not IL-12 p70, induces the expression of IL-16 in
      microglia and macrophages.
AB  - IL-16, a leukocyte chemoattractant factor (LCF), is involved in the disease
      process of multiple sclerosis and other autoimmune disorders. However, mechanisms
      by which this LCF is expressed are poorly understood. The present study
      underlines the importance of IL-12 p40 homodimer (p40(2)), the so-called
      biologically inactive molecule, in inducing the expression of IL-16 in primary
      mouse and human microglia, mouse BV-2 microglial cells, mouse peritoneal
      macrophages, and RAW264.7 cells. In contrast, IL-12 p70, the bioactive
      heterodimeric cytokine, was unable to induce the expression of IL-16 in any of
      these cell types. Similarly IL-12 p40(2) also induced the activation of IL-16
      promoter in microglia. Among various stimuli tested, p40(2) was the most potent
      one followed by p40 monomer, IL-16 and IL-23 in inducing the activation of IL-16
      promoter in microglial cells. Furthermore, induction of IL-16 mRNA expression by
      over-expression of p40, but not p35, cDNA and induction of IL-16 expression by
      p40(2) in microglia isolated from IL-12p35 (-/-) mice confirm that p40, but not
      p35, is responsible for the induction of IL-16. Finally, by using primary
      microglia isolated from IL-12Rbeta1 (-/-) and IL-12Rbeta2 (-/-) mice, we
      demonstrate that p40(2) induces the expression of this LCF via IL-12Rbeta1 but
      not IL-12Rbeta2. These results delineate a novel biological function of p40(2)
      and raise the possibility that biological function of IL-12 p40(2) may be
      different from IL-12 p70.

PMID- 19100624
TI  - The human complement fragment receptor, C5L2, is a recycling decoy receptor.
AB  - C5L2 is a 7 transmembrane domain receptor for complement fragment C5a that,
      unlike the classical C5a receptor, C5aR, does not couple to G proteins. However,
      in mice where C5L2 has been deleted, the response to C5a is altered, suggesting
      that C5L2 may have a signaling function. In order to investigate whether human
      C5L2 also has some capacity to transduce signals, we have attempted to produce a
      signaling competent form of human C5L2 by inserting C5aR sequences at three key G
      protein activation motifs. However, we detected neither an intracellular Ca(2+)
      response nor beta-arrestin redistribution in mutated C5L2, suggesting that the
      potential for G protein coupling is completely absent in this receptor and that,
      in humans, C5L2 may have functions that are unrelated to signaling. In
      confirmation of this, we detected constitutive ligand-independent internalization
      of C5L2 that resulted in the rapid accumulation of C5a and its stable metabolite,
      C5a des Arg, within the cell with only a small net change in cell surface
      receptor levels. Internalization was found to be through a clathrin-dependent
      mechanism that led to the retention and, in cells natively expressing C5L2, the
      degradation of the ligand within an intracellular compartment. In contrast, the
      classical C5a receptor, C5aR, internalized ligand much more slowly and a majority
      of this ligand was released back into the extracellular environment in an
      apparently undegraded form. These data suggest that a major function of human
      C5L2 is to remove active complement fragments from the extracellular environment.

PMID- 19100625
TI  - Infant penile tuberculosis following circumcision.
AB  - Primary penile tuberculosis associated with bilateral inguinal lymphadenopathy is
      described in a previously healthy 10-month old infant, who had been circumcised
      in Pakistan 4 months earlier. Mycobacterium tuberculosis was detected by acid
      fast stain, PCR and culture in specimens obtained from the penile ulcer and the
      excised inguinal lymph nodes.

PMID- 19100626
TI  - Pulmonary nodules caused by Schizophyllum commune after cardiac transplantation.
AB  - The incidence of pulmonary nodules after cardiac transplantation is not uncommon,
      and prompt diagnostic procedures are necessary to minimize disease-related
      morbidity and mortality. We report a 56-year-old woman who was found to have
      bilateral pulmonary nodules four months after cardiac transplantation. The
      microorganism was identified with a molecular diagnostic method as Schizophyllum
      commune, which had not been reported in English literature as a pathogen inducing
      pulmonary nodules after transplantation. She remained asymptomatic during the
      therapeutic period and the pulmonary nodules resolved six months later.

PMID- 19100628
TI  - Pax5 immunostaining in paraffin-embedded sections of canine non-Hodgkin lymphoma:
      a novel canine pan pre-B- and B-cell marker.
AB  - The Pax5 gene encodes the B-cell specific activator protein (BSAP), a member of
      the highly conserved paired box (PAX)-domain family of transcription factors and
      a key regulator in the development and differentiation of B-cells. Pax5 serves as
      a valuable B-cell marker in the classification of human lymphoma patients as it
      is restricted to lymphomas of B-cell lineage. In dogs, detection of Pax5 protein
      in lymphoma tissue has not been reported. Therefore, we have investigated the
      expression and detection of BSAP using a monoclonal anti-Pax5 antibody (anti
      BSAP, clone 24) in canine lymphoma tissue samples to evaluate its diagnostic
      relevance as a B-cell marker. A series of 25 lymph nodes from 23 canine non
      Hodgkin lymphoma patients, a reactive canine lymph node, and a normal non
      reactive canine lymph node, were evaluated. All B-cell non-Hodgkin lymphomas (15)
      were found to express Pax5 protein. In addition, there was a strong correlation
      between Pax5 and CD79a expression. Three CD3 positive and five CD3 and CD79a
      positive lymphomas were immunophenotypically negative for anti-Pax5, indicating a
      T-cell lineage. In conclusion, anti-Pax5 antibody may offer an excellent B-cell
      marker in canine lymphomas.

PMID- 19100627
TI  - Medical and substance use comorbidity in bipolar disorder.
AB  - OBJECTIVE: National Comorbidity Survey data indicate that bipolar disorder is
      characterized by high lifetime rates of co-occurring anxiety and substance use
      disorders (SUDs). Although compelling evidence suggests SUD comorbidity predicts
      non-response to treatment, the relationship between medical comorbidity and
      treatment response has not been studied adequately. In an attempt to understand
      the impact of medical comorbidity on treatment outcome, an analysis was conducted
      to inform the relationship between co-occurring medical illness, the
      phenomenology of bipolar disorder, and response to treatment with mood
      stabilizers. METHOD: A total of 98 adult outpatients with rapid-cycling bipolar I
      or II disorder and co-occurring SUDs were prospectively treated with the
      combination of lithium and valproate for up to 24 weeks. A logistic regression
      analysis was conducted to explore the relationship between phenomenology,
      response to mood stabilizers, and medical comorbidity as assessed by the
      Cumulative Illness Rating Scale (CIRS). High and low medical comorbidity burden
      were defined as a CIRS total score > or = 4 and < or = 3, respectively. RESULTS:
      Every patient enrolled into this study had at least 1 medical illness (most
      commonly respiratory, 72%) and on average had 4.9 different medical conditions.
      Over half of patients (52%) exhibited illnesses across four or more different
      organ systems, 24% had uncontrollable medical illnesses, and the mean overall
      total CIRS score was 5.56. The average body mass index (BMI) was 28.1 with 38%
      being overweight and 29% being obese. High medical burden was observed in 64% and
      was most strongly predicted by a diagnosis of bipolar I disorder (OR=34.9,
      p=0.002, 95%CI=3.9-316.1). A history of attempted suicide (OR=10.3, p=0.01,
      95%CI=1.7-62.0), a history of physical abuse (OR=7.6, p=0.03, 95%CI=1.3-45.7) and
      advancing age (OR=1.2, p<0.001, 95%CI=1.1-1.3) also independently predicted a
      high burden of general medical problems. Only 21% (N=21) of subjects enrolled
      into this study showed a bimodal response to treatment with lithium plus
      valproate, and neither BMI nor any summary CIRS measure predicted response.
      CONCLUSION: Rapid cycling with co-occurring substance use is not only associated
      with poor response to mood stabilizers, but is also a harbinger of serious
      medical problems. A high burden of medical comorbidity was associated with the
      bipolar I subtype, a history of attempted suicide, a history of physical abuse,
      and advancing age.

PMID- 19100629
TI  - Thermal stress treatment does not affect the stability and protective capacity of
      goat milk derived E2-marker vaccine formulation against CSFV.
AB  - Classical swine fever virus produces a huge mortality in infected herds during
      recurrent outbreaks, predominantly in tropical and subtropical areas. In this
      scenario, it is common that cold-chain related issues affect the efficacy of
      virus attenuated-derived vaccines, which are frequently used in eradication
      programs. In the present work, the stability and protective capacity of a
      recombinant vaccine preparation, based on goat milk derived E2 glycoprotein
      extracellular domain, were both analyzed after incubation at 4 degrees C or 37
      degrees C for 1 week. Differences in the viscosity and in the homodimeric form of
      the antigen were observed after comparing physicochemical properties of stressed
      and not stressed vaccine formulations. However, these differences did not affect
      the immunogenicity and protective capacity of such preparations. Noticeably, pigs
      immunized with the E2-based vaccine subjected to thermal stress became totally
      protected from the viral infection, after a challenge with 10(5) PLD(50) of a
      high virulent classical swine fever strain. This result supports the practical
      value of this vaccine preparation mostly for those regions in which cold-chain
      related failures tend to affect the protective capability of conventional virus
      attenuated vaccines.

PMID- 19100631
TI  - Recent methodological advances in the discovery of GPCR-associated protein
      complexes.
AB  - Protein-interaction networks have important roles in cellular homeostasis and the
      generation of complexity in biological systems. G-protein-coupled receptors
      (GPCRs), the largest family of membrane receptors and important drug targets, are
      integral parts of these networks. Ligand stimulation and the dynamic interaction
      with GPCR-associated protein complexes (GAPCs) constitute two important
      regulatory mechanisms of GPCR function. Several genomic and proteomic approaches
      have been developed to identify GAPCs in the past. However, this task turned out
      to be particularly demanding owing to difficulties in preserving the complex
      three-dimensional GPCR structure during receptor solubilization and to inherent
      limitations in the use of isolated receptor domains as bait. Newly emerging
      methods have the potential to overcome these limitations and will certainly boost
      the identification of functionally relevant GAPCs to finally increase our
      knowledge of the regulation of GPCRs and provide novel drug targets. Here, we
      focus on the comparison of two complementary GAPC purification strategies, which
      are based on soluble GPCR subdomains and entire GPCRs.

PMID- 19100630
TI  - A tale of two STAT6 knock out mice in the induction of experimental autoimmune
      encephalomyelitis.
AB  - T helper 2 (Th2) cytokines are known to be important in protection against
      experimental autoimmune encephalomyelitis (EAE). To investigate the role of the
      signal transducer and activator of transcription factor 6 (STAT6) in EAE we used
      mice with two different targeted disruptions of the STAT6 gene. In this report,
      we show that mice with a targeted deletion of the first coding exon of the SH2
      domain of STAT6 induce Th2 cell differentiation and are resistant to EAE
      induction. By contrast, STAT6(-/-) mice generated by deletion of amino acids 505
      to 584 encoding the SH2 domain of STAT6 are defective in Th2 cell differentiation
      and develop very severe EAE. These results suggest that an altered STAT6 gene can
      be more efficient than wild type STAT6 in regulating the autoimmune response in
      EAE.

PMID- 19100632
TI  - Cadmium and zinc uptake and toxicity in two strains of Microcystis aeruginosa
      predicted by metal free ion activity and intracellular concentration.
AB  - Microcystis aeruginosa is an important cyanobacteria widely found in numerous
      freshwater lakes. In this study, we examined the uptake and toxic effects of
      cadmium (Cd) and zinc (Zn) in non-toxic (Ma 469) and toxic (Ma 905) strains of
      Microcystis based on the metal free ion and cellular concentrations. We compared
      their uptake rates, pulse-amplitude-modulated parameters (maximum photosystem II
      quantum yield and operational quantum yield), cell-specific growth rates, and
      intracellular metal concentrations at different free Cd or Zn ion concentrations.
      Both strains exhibited a first-order uptake kinetics during the short-term (4h)
      uptake experiment no matter whether ethylenediaminetetraacetic acid (EDTA) or
      nitrilotriacetic acid (NTA) was added. The free ion activity model (FIAM)
      explained the short-term uptake of Cd or Zn, but failed to predict the long-term
      (48h) toxicity of Cd or Zn in the two strains. In contrast, the intracellular Cd
      or Zn concentration was more effective in explaining Cd or Zn toxicity in the two
      strains, indicating that the biotic ligand model (BLM) may be used to predict Cd
      or Zn toxicity in M. aeruginosa. Furthermore, the two strains exhibited similar
      sigmoid relationships between toxicity effects and intracellular Zn
      concentrations, but the Ma 905 was more tolerant of intracellular Cd toxicity
      than the Ma 469. Different Microcystis strains might have similar tolerance
      towards intracellular Zn toxicity. Our study provided important information for
      the assessment of metal toxicity in freshwater cyanobacteria.

PMID- 19100633
TI  - Effects of spaced retrieval training (SRT) on cognitive function in Alzheimer's
      disease (AD) patients.
AB  - Among the non-pharmacological treatments of dementia, SRT is a good candidate
      strategy for rehabilitating the cognition of AD patients. This study investigates
      the efficacy of SRT on the cognition of AD patients with very mild to mild
      disease. We administered 24-session SRT to 13 very mild and 6 mild AD patients.
      To assess the change of the neuropsychological performance after SRT, we
      performed the Korean version of the Consortium to Establish a Registry for
      Alzheimer's Disease neuropsychological battery (CERAD-K), the logical memory test
      (LMT), the Benton visual retention test A (BVRT-A), and the digit span test
      (DST). All tests were administered both before and after SRT. Retention spans
      were significantly increased up to 24 min after SRT in both very mild and mild AD
      patients (p<0.05), and this improvement was maintained for different sets of
      target information. Retainable words were also significantly increased after SRT
      in the very mild AD patients (p=0.007). However, we observed no changes in
      neuropsychological performance after SRT. Although we did not observe
      improvements in the neuropsychological tests following SRT, our results suggest
      that the treatment was an effective intervention for improving the memory of very
      mild to mild AD patients, and could potentially improve learning and retention
      outside the training session.

PMID- 19100634
TI  - Major depression as a potential trigger for Tako Tsubo cardiomyopathy.
AB  - Tako-Tsubo cardiomyopathy (TTC) is characterized by the sudden onset of severe
      left ventricular contractile dysfunction following profound emotional or physical
      stress. The underlying pathomechanism still remains to be elucidated. In this
      case we present a, to date, unique case of a female patient suffering from an
      episode of major depression who shows characteristic features of TTC.

PMID- 19100635
TI  - Long-term outcome after a first episode of heart failure. A prospective 7-year
      study.
AB  - BACKGROUND: Heart failure (HF) is a major issue of public health in contemporary
      aging populations. The objectives of the present study were to assess the long
      term survival of a contemporary cohort of patients discharged after a first
      hospitalization for HF and identify variables associated with adverse outcome.
      METHODS: We prospectively included consecutive patients (n=735) discharged from
      11 healthcare establishments of the Somme department (France) after a first
      hospitalization for HF during 2000. The 7-year observed survival was compared
      with the expected survival of the general population. RESULTS: Mean age of the
      study group was 75+/-12 years and 48% of patients were women. Left ventricular
      ejection fraction was measured in 628 patients (85%). During the 7-year follow
      up, 483 patients (67%) died. The 5- and 7-year observed survival rates were
      dramatically lower than the expected survival of the matched general population
      (42% vs. 70%, and 33% vs. 59%, respectively). Relative survival
      (observed/expected survival) was 60% at 5 years and 55% at 7 years. Multivariable
      analysis identified cancer, stroke, diabetes, prior myocardial infarction,
      chronic obstructive pulmonary disease, chronic atrial fibrillation, age, and
      hyponatraemia as independent predictors of 7-year mortality. CONCLUSIONS: In
      Europe, the long-term outcome of patients with new-onset HF is still extremely
      poor. Better implementation of guideline-oriented therapeutic strategies is
      needed to improve prognosis of this increasingly prevalent condition.

PMID- 19100636
TI  - Anomalous origin of the right coronary artery from the pulmonary artery (ARCAPA).
AB  - Anomalous origin of the right coronary artery from the pulmonary artery (ARCAPA)
      is a very rare congenital abnormality. Echocardiographic findings are specific
      but may be easily misinterpreted. We therefore present the case of a 5-year old
      boy with emphasis on the echocardiographic findings.

PMID- 19100637
TI  - Covered stents in the management of coarctation of the aorta in the adult:
      initial results and 1-year angiographic and hemodynamic follow-up.
AB  - BACKGROUND: The purpose of this study was to determine the safety and efficacy of
      the Cheatham Platinum covered stent in adults with coarctation of the aorta.
      METHODS: Adults with native coarctations (n=14); previous coarctation surgery
      (n=4), stenting (n=1) or both surgery and endovascular therapy (n=3) underwent
      percutaneous intervention with a covered stent. Indications for stenting in those
      with previous intervention were recurrent coarctation (n=4), aneurysm formation
      at the site of previous intervention (n=2) or both recurrent coarctation and
      aneurysm formation (n=2). RESULTS: Twenty-three covered stents were placed in 22
      patients (mean age 39+/-14 years, n=11 males). Successful device deployment was
      achieved in all patients, although one patient required a second covered stent
      for aortic wall rupture. Peak systolic gradient across the coarctation site
      decreased from 29+/-17 to 3+/-5 mm Hg (p<0.001) immediately following implant and
      this was maintained (6+/-9 mm Hg, p=0.001) at invasive assessment, 12 months
      after the initial procedure. Right arm systolic blood pressure significantly
      declined (p=0.02), as did the number of antihypertensive medications per patient
      (p=0.03). At angiographic follow-up, post-stenotic dilatation of the aorta
      decreased from 32+/-8 mm to 30+/-8 mm (p=0.001), however, no stent recoil was
      observed. CONCLUSIONS: Covered stents are safe, durable and efficacious in the
      management of coarctation of the aorta. Angiography and hemodynamic assessment is
      an effective method of screening for recurrent coarctation, and arch and vascular
      complications after stenting in adults.

PMID- 19100638
TI  - The honey man--second degree heart block after honey intoxication.
AB  - In October 2007, a 70-year-old Turkish patient presented to the emergency
      department of a Viennese state hospital with syncope. The electrocardiogram
      showed a second degree heart block type Wenckebach with intermittent 2:1
      conduction and preterminal negative T waves. There was no biochemical evidence of
      an acute ischemic cardiac event or any electrolyte imbalance. A coronary
      angiogram showed no evidence for coronary artery disease. During the first day of
      hospital admission, a jar of home made honey from the Black Sea region of Turkey
      is brought to the hospital by relatives of the patient. A commonly used household
      remedy in the eastern Black Sea region of Turkey, "bitter honey" or "mad honey"
      contains grayanotoxin from the nectar of Rhododendron luteum and Rhododendron
      ponticum. This is the first documented case of honey poisoning in the European
      Union where structural and ischemic causes have been excluded as possible reasons
      for the temporary AV-block. This case serves as a poignant reminder that
      physicians must demonstrate awareness of the cultural, social, and in this case
      toxicological, particularities of patients within immigrant populations.

PMID- 19100639
TI  - The molecular epidemiology of human and zoonotic Mycobacterium bovis: the
      intersection between veterinary medicine and public health.

PMID- 19100640
TI  - The value of a statistical life: a meta-analysis with a mixed effects regression
      model.
AB  - The value of a statistical life (VSL) is a very controversial topic, but one
      which is essential to the optimization of governmental decisions. We see a great
      variability in the values obtained from different studies. The source of this
      variability needs to be understood, in order to offer public decision-makers
      better guidance in choosing a value and to set clearer guidelines for future
      research on the topic. This article presents a meta-analysis based on 39
      observations obtained from 37 studies (from nine different countries) which all
      use a hedonic wage method to calculate the VSL. Our meta-analysis is innovative
      in that it is the first to use the mixed effects regression model [Raudenbush,
      S.W., 1994. Random effects models. In: Cooper, H., Hedges, L.V. (Eds.), The
      Handbook of Research Synthesis. Russel Sage Foundation, New York] to analyze
      studies on the value of a statistical life. We conclude that the variability
      found in the values studied stems in large part from differences in
      methodologies.

PMID- 19100641
TI  - Use of PET and PET/CT for radiation therapy planning: IAEA expert report 2006
      2007.
AB  - Positron Emission Tomography (PET) is a significant advance in cancer imaging
      with great potential for optimizing radiation therapy (RT) treatment planning and
      thereby improving outcomes for patients. The use of PET and PET/CT in RT planning
      was reviewed by an international panel. The International Atomic Energy Agency
      (IAEA) organized two synchronized and overlapping consultants' meetings with
      experts from different regions of the world in Vienna in July 2006. Nine experts
      and three IAEA staff evaluated the available data on the use of PET in RT
      planning, and considered practical methods for integrating it into routine
      practice. For RT planning, (18)F fluorodeoxyglucose (FDG) was the most valuable
      pharmaceutical. Numerous studies supported the routine use of FDG-PET for RT
      target volume determination in non-small cell lung cancer (NSCLC). There was also
      evidence for utility of PET in head and neck cancers, lymphoma and in esophageal
      cancers, with promising preliminary data in many other cancers. The best
      available approach employs integrated PET/CT images, acquired on a dual scanner
      in the radiotherapy treatment position after administration of tracer according
      to a standardized protocol, with careful optimization of images within the RT
      planning system and carefully considered rules for contouring tumor volumes. PET
      scans that are not recent or were acquired without proper patient positioning
      should be repeated for RT planning. PET will play an increasing valuable role in
      RT planning for a wide range of cancers. When requesting PET scans, physicians
      should be aware of their potential role in RT planning.

PMID- 19100642
TI  - Rectal dosimetry following prostate brachytherapy with stranded seeds--comparison
      of transrectal ultrasound intra-operative planning (day 0) and computed
      tomography-postplanning (day 1 vs. day 30) with special focus on sources placed
      close to the rectal wall.
AB  - BACKGROUND AND PURPOSE: The aim of the study was to compare intra-operative and
      postplanning at different intervals with special focus on sources placed close to
      the rectal wall. MATERIALS AND METHODS: In 61 consecutive patients, CT scans were
      performed on day 1 and day 30 after an I-125 implant with stranded seeds. The
      number of sources < or =7 mm to the rectal wall was determined, and displacements
      were analyzed. The angulation of strands relative to rectal wall was compared
      between intra-operative transrectal ultrasound (TRUS) and both postplanning CT
      scans. RESULTS: Sources close to the rectum on day 1 (n=204) have been the most
      apical in a strand in 98.5% (n=201). By comparing day 1 and day 30 data,
      significant inferior source displacements (mean 3.6 mm; p=0.02) relative to
      pelvic bones and a decreasing distance to the rectal wall (mean 1.2 mm; p<0.01)-
      consequentially increasing rectal dose--were determined only for sources
      initially > or =3 mm to the rectum. In contrast to an almost parallel arrangement
      of the needle track and the rectal wall in TRUS, strands and rectal wall
      converged towards the apex in the postplanning CT scans (mean >30 degrees).
      CONCLUSIONS: Posterior preplanning margins around the prostate should be
      particularly limited at the level of the prostate apex.

PMID- 19100643
TI  - Listeria monocytogenes in RTE foods marketed in Italy: prevalence and automated
      EcoRI ribotyping of the isolates.
AB  - The aims of the present study were: (a) to investigate the prevalence and the
      enumeration of Listeria monocytogenes in 200 samples of ready to eat (RTE) foods
      of animal and vegetal origin collected from different outlets and processing
      plants in Sardinia; (b) to characterize the isolates by phenotypical and
      molecular methods; (c) to analyze a subset of 42 L. monocytogenes by automated
      EcoRI ribotyping in order to predict the strain's potential virulence for humans.
      The strains were isolated from: smoked fish products, cooked marinated products,
      meat products and pre-packaged mixed vegetable salads. Of the samples tested, 22%
      were positive for Listeria spp. The prevalence of L. monocytogenes was 9.5%,
      while the level of L. monocytogenes in the positive samples was <10 cfu/g in
      94.7% of cases. EcoRI ribotyping differentiated the isolates into 16 distinct
      ribotypes (similarity>93%), belonging to 17 different DuPont Identification
      Library Codes (DUP-IDs) clones. The Simpson's numerical index of discrimination
      was 0.911. Cluster analysis pointed out a high similarity among strains isolated
      from meat, fish, and vegetables of different origin. These results confirmed the
      existence of a widespread population of L. monocytogenes, characterized by highly
      related strains existing in different geographical areas. 65% of these strains
      belonged to lineage II (serotypes 1/2a and 1/2c), subtypes known to be associated
      with sporadic human listeriosis outbreaks. The remaining 35% of the isolates
      (serotypes 1/2b, 3b and 4b) were allocated to lineage I and belong to distinct
      clonal groups (DUP-ID 1038 and 1042), which again have been associated with
      several outbreaks of human listeriosis. Neither atypical profiles nor lineage III
      strains were found. EcoRI ribotyping was confirmed as a rapid and reliable method
      for L. monocytogenes typing, providing useful data for epidemiologic and
      clonality surveys of L. monocytogenes strains isolated from RTE foods.

PMID- 19100644
TI  - Type 1 diabetes, the A1 milk hypothesis and vitamin D deficiency.
AB  - The 'A1' genetic variant of beta-casein in milk has been linked to type 1
      diabetes (T1D). The keystone piece of supporting evidence is an ecological study
      positively correlating the incidence of T1D with amount of A1 beta-casein
      consumption per capita. Of relevance, A1 beta-casein consumption is also
      positively correlated with latitude, itself implicated in T1D through vitamin D
      deficiency. Ecological and biological evidence convincingly implicate vitamin D
      deficiency in T1D. Latitude is a confounder of the ecological data that underpin
      the hypothesis that A1 beta-casein in cow's milk is a causative factor in T1D.

PMID- 19100645
TI  - Retinal vessel response to flicker light in children and adolescents with type 1
      diabetes mellitus and overweight or obesity.
AB  - It was the goal of the trial to assess cardiovascular risk factors in children
      and adolescents with type 1 diabetes mellitus or overweight/obesity. All children
      and adolescents (n=77 [n=45 patients with diabetes mellitus, n=32 patients with
      overweight/obesity]) admitted to our hospital during the period from 01/07 to
      31/08/2006 were included in the trial. Socio-demographic and laboratory data
      (age, sex, diabetes duration, BMI, BMI-SDS, HbA1c, fasting blood glucose, oGTT in
      patients with overweight/obesity, lipids, CRP, TSH, creatinine, and
      microalbuminuria) were assessed. The diameter of a retinal arterial and a venous
      segment was measured continuously on-line with a Dynamic Vessel Analyzer, carotid
      intima-media thickness (IMT) was measured, and 24-h-blood pressure monitoring was
      applied. RESULTS: Flicker light stimulation induces a comparable arterial
      dilatation in patients with type 1 diabetes and overweight/obesity. Univariate
      ANOVA in patients with type 1 diabetes shows an influence of diastolic blood
      pressure on arterial dilatation. Other factors such as BMI, age, diabetes
      duration, smoking, sex, HbA1c and insulin dose/kg had no effect. CONCLUSIONS: In
      children and adolescents with diabetes or overweight/obesity retinal vascular
      alterations seem to be more sensitive and already present before the occurrence
      of classic cardiovascular markers.

PMID- 19100646
TI  - The VEGF-system in primary pulmonary angiosarcomas and haemangioendotheliomas:
      new potential therapeutic targets?
AB  - Malignant epitheloid vascular tumors (epitheloid haemangioendotheliomas and
      angiosarcomas) of the lung are very rare lesions often posing difficulties in
      diagnosis. Due to their rare incidence no standardized therapy regimen is
      established. Surgical resection of the tumor is the mainstay of treatment, but in
      many cases, especially due to the multifocality of the tumor, negative resection
      margins cannot be achieved. A blockade of members of the vascular endothelial
      growth factor (VEGF) system either by antibodies for their ligands or by kinase
      inhibitors has been increasingly used for the therapy of solid tumors. The aim of
      our study was to highlight the main distinguishing morphological factors between
      the two entities for diagnostic purposes. Next, we investigated several factors
      of the VEGF-signalling pathway as well as Tie 2 in eight primary pulmonary
      epitheloid haemangioendotheliomas and ten primary pulmonary epitheloid
      angiosarcomas by means of immunohistochemistry using commercially available
      antibodies against VEGF-A, VEGF-B, VEGF-C, VEGF-D, VEGFR-2, VEGFR-3 and
      endothelium specific kinase Tie2. The observed positivity for the factors of the
      VEGF-signalling pathway points towards a possible new therapeutic option in the
      therapy of pulmonary vascular tumors by a blockade of the ligands or their
      receptors.

PMID- 19100647
TI  - A multicenter randomized phase II study of the irinotecan/gemcitabine doublet
      versus irinotecan monotherapy in previously treated patients with extensive stage
      small-cell lung cancer.
AB  - OBJECTIVES: To compare the efficacy and safety profile of irinotecan (I) versus
      the combination of irinotecan/gemcitabine (IG) as second-line treatment of
      patients with extensive stage small-cell lung cancer (SCLC). TREATMENT: Patients
      with SCLC who have received at least one chemotherapy regimen were randomized to
      receive either the IG regimen (gemcitabine 1000mg/m(2) intravenous (i.v.) on days
      1 and 8 and irinotecan 300mg/m(2) i.v. on day 8) or I monotherapy (300mg/m(2)
      i.v. on day 1) both every 3 weeks. RESULTS: Thirty-eight patients were enrolled
      in the IG and 31 in the I arm. Due to slow accrual an early closure of the study
      was decided. Response rate was significantly higher in the IG than in I arm
      (23.7% vs. 0%; p=0.004). The median time to progression (TTP) was 3.9 months
      (range: 0.5-14.5 months; 95% CI: 1.4-6.6) and 1.7 months (range: 0.5-9.9 months;
      95% CI: 1.2-2.3) (p=0.010) for the IG and I arms, respectively. There was no
      difference in terms of median overall survival between the two arms (6.8 months
      and 4.6 months for the IG and I arm, respectively). The most frequent toxicities
      were grade III/IV neutropenia and grade III/IV diarrhea. CONCLUSIONS: Although
      the IG regimen seems to be more active than the I monotherapy, the premature
      closure of the study prevents the drawing of definitive conclusions.

PMID- 19100648
TI  - Surgical resection for metastatic non-small cell lung cancer to the pancreas.
AB  - We report the case of a woman with non-small cell lung cancer (NSCLC) metastatic
      to the pancreas who underwent pancreatic resection followed by a significant
      disease-free interval. Resection of NSCLC metastases, other than those to the
      brain and adrenal gland, are rarely reported. We could not identify any other
      cases of pancreatic metastasis resection in the literature. This case proves, in
      principle, that resection of solitary metastatic lesions in certain clinical
      conditions can be improved regardless of location.

PMID- 19100649
TI  - Male lactation: why, why not and is it care?
AB  - Mammals are characterised by their ability to provision offspring with milk, but
      lactation is normally restricted to females. Why do most males not share this
      trait? The morphological and physiological modifications necessary for male
      lactation are possible and, although restrictive, the ecological factors that
      could select for male lactation seem common enough. Until quite recently, there
      was no evidence for male lactation in wild mammals, but it has now been reported
      in two species of Old World fruit bats. Here we review mechanisms that can cause
      milk production in males and also consider the possibility that male lactation in
      these bats is a unique adaptive phenomenon.

PMID- 19100650
TI  - Darwin in disguise.
AB  - Darwinism appears in many more academic areas than just evolutionary biology. New
      disciplines are created out of its fusion with existing fields of study. However,
      this practise is criticised for a lack of evidence-based justification, and for
      adopting gene-oriented reductionism in the social sciences. This article briefly
      considers seven examples of new disciplines for which Darwinism has been
      appropriated. In each case, succinct background information precedes quotes
      provided for this purpose by a leading researcher.

PMID- 19100651
TI  - The complex origins of domesticated crops in the Fertile Crescent.
AB  - A combination of genetics and archaeology is revealing the complexity of the
      relationships between crop plants and their wild ancestors. Archaeobotanical
      studies are showing that acquisition of the full set of traits observed in
      domesticated cereals was a protracted process, intermediate stages being seen at
      early farming sites throughout the Fertile Crescent. New genetic data are
      confirming the multiregional nature of cereal domestication, correcting a
      previous view that each crop was domesticated by a rapid, unique and
      geographically localised process. Here we review the evidence that has prompted
      this reevaluation of the origins of domesticated crops in the Fertile Crescent
      and highlight the impact that this new multiregional model is having on modern
      breeding programmes.

PMID- 19100652
TI  - Systems biology spins off a new model for the study of canalization.
AB  - The tools of systems biology make possible the study of phenotypic robustness at
      the molecular level. A recent investigation by Ansel et al. shows that alleles
      with different capabilities to buffer noise in gene expression - variation in
      protein abundance among genetically identical cells - segregate in populations of
      budding yeasts. These findings show that there is raw material for robust gene
      expression to evolve by natural selection, enabling the study of canalization of
      gene networks as it evolves in nature.

PMID- 19100653
TI  - Oil palm: disinformation enables deforestation.

PMID- 19100654
TI  - The evolution of restricted recombination in sex chromosomes.
AB  - In species with separate sexes, sex determination often has a genetic basis, and
      in a wide diversity of taxa a pair of cytologically distinguishable 'sex
      chromosomes' are found such that the chromosome complements of males and females
      differ (males are often XY and females XX, but sometimes females are ZW whereas
      males are ZZ). Recent evidence from sequences of sex-linked genes confirms
      classical genetic evidence that these chromosomes are a homologous pair, evolved
      from a normal chromosome pair, between which recombination stopped. We discuss
      why sex chromosomes evolve reduced recombination and why different parts of the
      chromosomes stopped recombining at different times, and outline some of the
      consequences of suppressed recombination, including the evolution of chromosome
      heteromorphism.

PMID- 19100655
TI  - DNA barcoding for ecologists.
AB  - DNA barcoding - taxon identification using a standardized DNA region - has
      received much attention recently, and is being further developed through an
      international initiative. We anticipate that DNA barcoding techniques will be
      increasingly used by ecologists. They will be able to not only identify a single
      species from a specimen or an organism's remains but also determine the species
      composition of environmental samples. Short DNA fragments persist in the
      environment and might allow an assessment of local biodiversity from soil or
      water. Even DNA-based diet composition can be estimated using fecal samples. Here
      we review the new avenues offered to ecologists by DNA barcoding, particularly in
      the context of new sequencing technologies.

PMID- 19100656
TI  - Alleviation of salinity stress on wheat yield, yield components, and nutrient
      uptake using arbuscular mycorrhizal fungi under field conditions.
AB  - We conducted this study because of the importance of salinity in many parts of
      the world, and because almost all research regarding the effects of arbuscular
      mycorrhiza (AM) on plant growth under salinity have been conducted under
      greenhouse conditions. The hypothesis was that, with respect to the great
      abilities of AM fungi under stress, they are able to alleviate salinity stress
      under field conditions. Hence, the objectives were to evaluate the effects of
      different species of arbuscular mycorrhizal fungi on: (1) the yield and yield
      components of different wheat cultivars, and (2) nutrient uptake of different
      wheat genotypes under field saline conditions. The soil salinity of 7.41dS/m and
      three AM species including Glomus etunicatum, G. mosseae and G. intraradices and
      wheat genotypes of Roshan, Kavir and a mutated line of Tabasi were tested. The
      electrical conductivity of the irrigation water was 13.87dS/m. Under salinity, AM
      species significantly increased the growth and nutrient uptake of the mutated
      Tabasi line compared with the other genotypes, especially in comparison to the
      Kavir genotype. The mycorrhizal Tabasi genotype resulted in the lowest
      concentrations of Na(+) and Cl(-). The influence of different species of AM on
      enhancing plant growth under salinity was observed in the following order: Glomus
      etunicatum>G. mosseae>G. intraradices. The symbiosis of Glomus etunicatum and G.
      intraradices with the Tabasi mutated line resulted in the highest (42.08%) and
      the lowest (7.55%) increases in wheat dry weight, respectively. The highest
      (38.3%) and the lowest (4.5%) grain yield increases were related to the symbiosis
      of Tabasi mutated line with Glomus etunicatum and G. intraradices, respectively.
      Although different species of AM can be very beneficial to wheat plants under
      salinity stress, it is obvious from the results of this research that Glomus
      etunicatum can perform more efficiently under such conditions compared with other
      AM species. This indicates the great importance of selecting the right
      combination of AM species and host plant to make cultivation under salinity even
      more likely.

PMID- 19100657
TI  - Genistein and changes of resting and action potentials in Conocephalum conicum.
AB  - Genistein (4',5,7-trixydroxyflavone) is a member of the family of plant
      flavonoids that widely occurs in crop plants. It is involved in a wide spectrum
      of pharmacological activities, and is suggested to have anti-cancer dietary
      properties. Cell membranes are one of the targets of anti-cancer drugs. In the
      present study, we used the liverwort Conocephalum conicum as a model plant in an
      electrophysiological study. Intracellular microelectrode measurements were
      carried out to examine the effects of genistein alone and in combination with
      verapamil on resting and action potentials. The application of isoflavone
      genistein resulted in a statistically significant elevation in action potential
      amplitudes. An increase of 13-62% compared with the control was noted. An
      increase was also found in the membrane resting potentials in genistein-treated
      plants. Verapamil, the known calcium channel inhibitor, caused a gradual decline
      of AP amplitudes, whereas preincubation of Conocephalum thalli with genistein
      prevented inhibition of APs by verapamil. It is concluded that genistein strongly
      affects the membranes, and the effect of genistein in canceling the activity of
      verapamil is discussed.

PMID- 19100658
TI  - Association between an index of consumption of hand-rub solution and the
      incidence of acquired meticillin-resistant Staphylococcus aureus in an intensive
      care unit.

PMID- 19100659
TI  - Bacillus cereus heteroresistance to carbapenems in a cancer patient.

PMID- 19100660
TI  - Washing toys in a neonatal intensive care unit decreases bacterial load of
      potential pathogens.

PMID- 19100661
TI  - Meticillin-resistant Staphylococcus aureus contamination of healthcare workers'
      uniforms in long-term care facilities.
AB  - Meticillin-resistant Staphylococcus aureus (MRSA) and other multiply resistant
      bacteria are frequently isolated in long-term care facilities (LTCFs). This study
      evaluated the contamination of staff clothing in three LTCFs. Over 500 samples
      were taken from uniforms and their pockets and these samples showed a high level
      of MRSA contamination. Wearing plastic aprons and managing pocket contents
      improved the contamination rate. Our results highlight the continued importance
      of hand hygiene, since staff have frequent contact with their uniforms and could
      potentially contaminate their hands before care.

PMID- 19100662
TI  - Abnormal differentiation of newborn granule cells in age-related working memory
      impairments.
AB  - Age-related declines in spatial memory have been linked to abnormal functional
      properties and connectivity of newborn granule cells. However, the relationship
      between adult neurogenesis, aging, and cognitive performance seems more complex
      than previously anticipated, likely due to the difficulty of disentangling
      alterations related to training as such and those associated with cognitive
      performance. Here, we investigated how different aspects of adult neurogenesis
      might be related to training, age and cognitive performance amongst aged subjects
      by comparing behaviourally naive and tested rats of 3, 6, 24mo of age. We
      separated aged rats into learning-impaired and -unimpaired groups based on their
      performance in the Morris water maze to investigate neurogenesis-related
      morphological and neurochemical changes. We report an age-related decline in cell
      proliferation and maturation independent of cognitive performance and testing. We
      confirm an age-related altered differentiation of newborn neurons which was
      particularly prominent in learning-impaired rats. This was associated with an
      abnormally prolonged expression of the early progenitor marker Nestin,
      potentially also affecting maturation, survival/integration of newborn neurons
      into existing neuronal networks, which might underlie the individual differences
      in cognitive performance during aging.

PMID- 19100663
TI  - [DRESS syndrome caused by phenylbutazone].
AB  - The drug rash with hypereosinophilia and systemic symptoms (DRESS) syndrome is a
      severe drug-induced hypersensitivity syndrome. We report a 57-year-old woman
      suffering from a DRESS syndrome 15 days after phenylbutazone exposure. She had a
      skin eruption, liver involvement and hypereosinophilia. She fully recovered after
      drug withdrawal.

PMID- 19100664
TI  - [Usefulness of brain natriuretic peptide and N-terminal pro-brain natriuretic
      peptide in the elderly].
AB  - B-type natriuretic peptide and N-terminal pro-brain natriuretic peptide are
      biomarkers secreted both in response to myocardial stretch and increased
      ventricular wall stress. They are now largely used in cardiovascular disease in
      adults, especially as diagnostic and prognostic tools. This article aims at
      synthesizing existing data concerning the usefulness of natriuretic peptides in
      elderly patients. With aging, co-morbidities such as renal failure are common and
      lead to an increase in circulating concentrations of natriuretic peptides.
      Nevertheless, their usefulness is relevant in geriatric practice. Their role has
      been well established in heart failure, not only in diagnosis, using two
      thresholds to decrease misclassification, but also in prognosis. In the future,
      natriuretic peptides could be used as prognosis tools in acute coronary syndrome,
      in cardiovascular risk assessment or in management of heart valve disease.
      However, further investigations in elderly people are needed before validating
      these indications in routine geriatric practice.

PMID- 19100665
TI  - Transfer parameter values in temperate forest ecosystems: a review.
AB  - Compared to agricultural lands, forests are complex ecosystems as they can
      involve diverse plant species associations, several vegetative strata
      (overstorey, shrubs, herbaceous and other annual plant layer) and multi-layered
      soil profiles (forest floor, hemi-organic and mineral layers). A high degree of
      variability is thus generally observed in radionuclide transfers and
      redistribution patterns in contaminated forests. In the long term, the soil
      compartment represents the major reservoir of radionuclides which can give rise
      to long-term plant and hence food contamination. For practical reasons, the
      contamination of various specific forest products has commonly been quantified
      using the aggregated transfer factor (T(ag) in m(2)kg(-1)) which integrates
      various environmental parameters including soil and plant type, root distribution
      as well as nature and vertical distribution of the deposits. Long lasting
      availability of some radionuclides was shown to be the source of much higher
      transfer in forest ecosystems than in agricultural lands. This study aimed at
      reviewing the most relevant quantitative information on radionuclide transfers to
      forest biota including trees, understorey vegetation, mushrooms, berries and game
      animals. For both radiocaesium and radiostrontium in trees, the order of
      magnitude of mean T(ag) values was 10(-3)m(2)kg(-1) (dry weight). Tree foliage
      was usually 2-12 times more contaminated than trunk wood. Maximum contamination
      of tree components with radiocaesium was associated with (semi-)hydromorphic
      areas with thick humus layers. The transfer of radionuclides to mushrooms and
      berries is high, in comparison with foodstuffs grown in agricultural systems.
      Concerning caesium uptake by mushrooms, the transfer is characterized by a very
      large variability of T(ag), from 10(-3) to 10(1)m(2)kg(-1) (dry weight). For
      berries, typical values are around 0.01-0.1 m(2)kg(-1) (dry weight). Transfer of
      radioactive caesium to game animals and reindeer and the rate of activity
      reduction, quantified as an ecological half-life, reflect the soil and pasture
      conditions at individual locations. Forests in temperate and boreal regions
      differ with respect to soil type and vegetation, and a faster decline of muscle
      activity concentrations in deer occurs in the temperate zone. However, in wild
      boar the caesium activity concentration shows no decline because of its special
      feeding habits. In the late phase, i.e. at least a few months since the external
      radionuclide contamination on feed plants has been removed, a T(ag) value of 0.01
      m(2)kg(-1) (fresh weight) is common for (137)Cs in the muscles of adult moose and
      terrestrial birds living in boreal forests, and 0.03 m(2)kg(-1) (fresh weight)
      for arctic hare. Radiocaesium concentrations in reindeer muscle in winter may
      exceed the summer content by a factor of more than two, the mean T(ag) values for
      winter ranging from 0.02 to 0.8 m(2)kg(-1) (fresh weight), and in summer from
      0.04 to 0.4m(2)kg(-1). The highest values are found in the year of initial
      contamination, followed by a gradual reduction. In waterfowl a relatively fast
      decline in uptake of (137)Cs has been found, with T(ag) values changing from 0.01
      to 0.002 m(2)kg(-1) (fresh weight) in the three years after the contaminating
      event, the rate being determined by the dynamics of (137)Cs in aquatic
      ecosystems.

PMID- 19100666
TI  - Bilateral maxillary sinus fungus ball: report of a case.

PMID- 19100667
TI  - Obese women's experiences of encounters with midwives and physicians during
      pregnancy and childbirth.
AB  - OBJECTIVE: to describe obese women's experiences of encounters with midwives and
      physicians during pregnancy and childbirth. DESIGN: a qualitative study using a
      phenomenological approach. Data were collected by means of interviews that were
      tape-recorded. SETTING: the women's homes or at a hospital in western Sweden.
      PARTICIPANTS: 10 women with body mass index >30, three primiparous and seven
      multiparous, who had given birth at a hospital in western Sweden in the period
      between October 2006 and September 2007 were interviewed four to six weeks after
      childbirth. FINDINGS: the meaning of being both obese and pregnant is living with
      a constant awareness of the body, and its constant exposure to the close
      observation and scrutiny of others. It involves negative emotions and experiences
      of discomfort. Feelings of discomfort increase as a result of humiliating
      treatment, whilst affirmative encounters alleviate discomfort and provide a sense
      of wellbeing. CONCLUSION AND IMPLICATIONS FOR PRACTICE: obese pregnant women are
      a vulnerable group because obesity is highly visible. Caregivers tend to focus on
      providing care to obese patients somatically, but are additionally in need of
      knowledge about care from the woman's point of view. Many obese women have
      negative experiences of health care that they have to overcome. It is necessary
      to individualise care for obese pregnant women, which involves taking time to
      give the women an opportunity to tell their own story. Caregivers have to promote
      health but it has to be done honestly and respectfully. In order to avoid
      judgemental attitudes and causing increased suffering for obese pregnant women,
      midwives and physicians need to be conscious of, reflect upon and verbalise their
      own attitudes and power.

PMID- 19100668
TI  - Allocation and source attribution of lead and cadmium in maize (Zea mays L.)
      impacted by smelting emissions.
AB  - Plants grown in contaminated areas may accumulate trace metals to a toxic level
      via their roots and/or leaves. In the present study, we investigated the
      distribution and sources of Pb and Cd in maize plants (Zea mays L.) grown in a
      typical zinc smelting impacted area of southwestern China. Results showed that
      the smelting activities caused significantly elevated concentrations of Pb and Cd
      in the surrounding soils and maize plants. Pb isotope data revealed that the
      foliar uptake of atmospheric Pb was the dominant pathway for Pb to the leaf and
      grain tissues of maize, while Pb in the stalk and root tissues was mainly derived
      from root uptake. The ratio of Pb to Cd concentrations in the plants indicated
      that Cd had a different behavior from Pb, with most Cd in the maize plants coming
      from the soil via root uptake.

PMID- 19100669
TI  - Silicate nephrolithiasis after ingestion of supplements containing silica
      dioxide.
AB  - Silicate calculi are common in some mammals, such as dogs and sheep, but
      extremely rare in humans. We report a case of silicate calculi in a woman using
      oral over-the-counter Uncaria tomentosa, Digestive Advantage and FlexProtex
      supplements. All 3 contained the excipient silica dioxide. Stone analysis showed
      composition of 100% silicate. The nephrolithiasis promptly abated after
      discontinuation of the products containing silica, then returned when the patient
      restarted her supplements. This case emphasizes the importance of stone analysis
      when obvious causes of nephrolithiasis are unclear and highlights the concerns of
      using over-the-counter supplements without substantial oversight.

PMID- 19100670
TI  - Renal vascular endothelial function in hypertensive patients with type 2 diabetes
      mellitus.
AB  - BACKGROUND: Basal nitric oxide (NO) activity has a pivotal role in the regulation
      of glomerular hemodynamics, and in animal experiments, its alteration has been
      associated with morphological changes characteristic of diabetic nephropathy.
      STUDY DESIGN: Prospective observational-study during a mean follow-up of 2.1
      years. SETTING & PARTICIPANTS: 66 hypertensive patients (aged 30 to 80 years)
      with type 2 diabetes and estimated glomerular filtration rate (GFR) greater than
      80 mL/min/1.73 m(2) with normoalbuminuria or microalbuminuria. PREDICTOR: Mean
      arterial pressure during follow-up during treatment with telmisartan or ramipril
      for 9 weeks, followed by treatment according to the discretion of the individual
      primary care physician. OUTCOMES & MEASUREMENTS: Renal vascular resistance, renal
      plasma flow, GFR, and change in renal plasma flow in response to infusion of the
      NO synthase inhibitor N-monomethyl-L-arginine as an indicator of basal NO
      activity in the renal vasculature. RESULTS: 50 of 66 patients could be
      reexamined. At follow-up, mean arterial pressure decreased from 106 +/- 9.1 to
      100 +/- 11 mm Hg (P < 0.001). Body mass index and hemoglobin A(1c) levels were
      unaltered. Renal vascular resistance decreased (from 128 +/- 44 to 103 +/- 30 mm
      Hg/mL/min/1.73 m(2); P < 0.001), renal plasma flow increased (from 490 +/- 133 to
      589 +/- 154 mL/min/1.73 m(2); P < 0.001), and GFR did not change (113 +/- 22
      versus 116 +/- 26 mL/min/1.73 m(2); P = 0.4) during follow-up. The decrease in
      renal plasma flow in response to N-monomethyl-l-arginine infusion was more
      pronounced at follow-up (-56.7 +/- 39 versus -73.4 +/- 48 mL/min/1.73 m(2); P =
      0.02), indicating improved basal NO activity. After adjustment for possible
      confounders, patients with a marked decrease in mean arterial pressure showed
      more improved basal NO activity during follow-up than those with a less
      pronounced decrease in mean arterial pressure (P = 0.04). LIMITATIONS: Patients
      were treated according to the discretion of the individual primary care
      physician. CONCLUSIONS: During follow-up, renal vascular resistance, renal plasma
      flow, and renal endothelial function (indicated by basal NO activity) improved.
      Better blood pressure control was associated with improved endothelial function
      of the renal vasculature, thereby potentially mediating the changes in renal
      hemodynamics.

PMID- 19100671
TI  - Association between oral sodium phosphate bowel preparations and kidney injury: a
      systematic review and meta-analysis.
AB  - BACKGROUND: Case reports and series have suggested an association between oral
      sodium phosphate bowel preparations and kidney injury. Results of analytic
      studies have been mixed. STUDY DESIGN: Systematic review and meta-analysis.
      SETTING & POPULATION: Patients receiving sodium phosphate bowel preparations (or
      comparators) in anticipation of colonoscopy. SELECTION CRITERIA FOR STUDIES:
      Primary data reports of controlled studies of the effects of oral sodium
      phosphate versus comparator on kidney function. PREDICTOR: Receipt of oral sodium
      phosphate bowel purgative. OUTCOMES: Random-effects pooled odds ratio for kidney
      injury in oral sodium phosphate-treated patients. RESULTS: Seven studies met
      criteria for inclusion. Significant heterogeneity existed in the populations
      under study (colonoscopy indication, baseline kidney function, and demographics),
      methods used (control group and use of prophylactic hydration), definition of
      kidney injury used (timing and magnitude), and results observed. The pooled odds
      ratio for kidney injury in oral sodium phosphate-treated patients ranged from
      1.08 (95% confidence interval, 0.71 to 1.62) to 1.22 (95% confidence interval,
      0.77 to 1.92). No obvious study- or patient-level factors that explained
      interstudy heterogeneity were identified. LIMITATIONS: Few studies, each of
      limited quality. CONCLUSIONS: Based on existing data, it is not possible to
      discern whether there is an association between receipt of oral sodium phosphate
      and kidney injury. Future investigation should be aimed at clarifying this
      association and examining the roles of prophylactic hydration and baseline kidney
      function on any imposed risk. Future work would be greatly enhanced by a
      standardized definition of incident kidney injury.

PMID- 19100672
TI  - Hospital performance and differences by kidney function in the use of recommended
      therapies after non-ST-elevation acute coronary syndromes.
AB  - BACKGROUND: Chronic kidney disease (CKD) is associated with an increased risk of
      cardiac events and death; however, underuse of guideline-recommended therapies is
      widespread. The extent to which hospital performance affects the care of patients
      with CKD and non-ST-segment elevation acute coronary syndromes (NSTE ACSs) is
      unknown. STUDY DESIGN: Observational cohort. SETTING & PARTICIPANTS: 81,374
      patients with NSTE ACSs treated at 327 US hospitals. PREDICTOR: Hospital
      performance, measured by quartiles of composite adherence to American Heart
      Association class I guidelines for therapy acutely (aspirin, beta-blockers,
      clopidogrel, heparin, and glycoprotein IIb/IIIa inhibitors) and at discharge
      (aspirin, clopidogrel, angiotensin-converting enzyme inhibitors, and lipid
      lowering agents) in eligible patients. OUTCOMES & MEASUREMENTS: Use of each
      American Heart Association class I acute and discharge therapy stratified by
      continuous estimated glomerular filtration rate (eGFR). Multivariable models were
      adjusted for demographics, clinical factors, and hospital features. RESULTS:
      Better-performing hospitals had lower prescribing rates for most therapies (5 of
      9) with lower levels of kidney function, whereas lower-performing hospitals were
      more likely to have similar prescribing rates across the eGFR spectrum,
      suggesting that prescribing patterns at these hospitals were insensitive to
      differences in eGFR. LIMITATIONS: Observational design, selection bias of study
      cohort. CONCLUSION: Patients with lower levels of kidney function admitted with
      NSTE ACSs are less likely to receive evidence-based therapies. Treatment
      disparities related to CKD are most evident at top-performing hospitals.

PMID- 19100673
TI  - Does degree of asymmetry relate to performance? An investigation of word
      recognition and reading in consistent and mixed handers.
AB  - Is it advantageous to be strongly lateralized? The current study investigated
      this question by examining the relationship between visual field asymmetries for
      lexical tasks and reading performance in a sample of 200 young adults. Larger
      visual field asymmetries were associated with better reading performance, but
      this relationship was obtained primarily in those with strong and consistent hand
      preferences. Among mixed handers, variation in visual field asymmetry accounted
      for little or no variance in reading skill. In addition, correlations between
      visual field asymmetry and reading performance were observed for word recognition
      tasks, but not for tasks requiring controlled semantic retrieval. The results are
      consistent with the idea that consistent and mixed handers may represent
      differing neurobehavioral populations. Because greater lateralization was
      associated with better reading skill only for consistent handers, reduced
      behavioral asymmetry cannot be assumed to be a risk factor for reading
      dysfunction in the population as a whole.

PMID- 19100674
TI  - Re-intervention on crowns: what comes next?
AB  - AIM: It is the aim of this paper to consider the treatment instituted when re
      intervention is deemed necessary on a tooth which has previously been crowned.
      METHODS: A detailed sample of treatment records of patients has been established
      at the NHS Business Services Authority (Dental Services Division), consisting of
      records containing indirectly placed restorations for patients of age 18 years or
      older from January 1991. For each tooth treated with a crown, the subsequent
      history of intervention on that tooth was recorded. RESULTS: There were data on
      47,474 crowns available for analysis, with metal-ceramic (bonded) crowns
      dominating the data (overall, 80% of crowns being these). There were 10,426
      crowned teeth with re-interventions in the study period, with 36% of the re
      interventions involving recementing, 17% being replacement crowns, 13% direct
      restorations, 12% root treatment, and 19% of crowned teeth being extracted and/or
      replaced by a denture. The longer the interval since crown placement, the higher
      the proportion of extractions or direct restoration and the lower the proportion
      of recementing. CONCLUSIONS: Recementation is the most frequently recorded re
      intervention, with the incidence of this decreasing with increasing age of the
      crown. In 17% of re-interventions, the next intervention was a replacement crown.

PMID- 19100675
TI  - Erythropoietin-induced phosphorylation/degradation of BIM contributes to survival
      of erythroid cells.
AB  - OBJECTIVE: A proapoptotic BH3-only protein BIM (BCL-2 interacting mediator of
      cell death) can link cytokine receptor signaling with the apoptotic machinery in
      hematopoietic cells. We investigated here the role of BIM in erythropoietin (EPO)
      mediated survival in erythroid cells. MATERIALS AND METHODS: We downregulated BIM
      in EPO-dependent HCD57 erythroid cells with short hairpin RNA (shRNA), and used
      real-time polymerase chain reaction, Western blots, and flow cytometry to
      characterize BIM expression and apoptosis. Hematologic analyses of BIM-deficient
      (Bim(-/-)) mice were conducted. RESULTS: BIM expression increases in primary
      murine erythroid cells and HCD57 cells deprived of EPO. Whereas Bim mRNA
      increased less than twofold, BIM protein increased more than 10-fold after EPO
      withdrawal, suggesting posttranscriptional regulation of BIM. EPO treatment
      resulted in rapid phosphorylation of BIM at Serine 65 and phosphorylation
      correlated with degradation of BIM. Inhibition of extracellular signal-regulated
      kinase (ERK) by a MEK/ERK inhibitor, U0126, blocked both phosphorylation and
      degradation of BIM, resulting in apoptosis. Treatment with a proteasome
      inhibitor, MG-132, also blocked degradation of phosphorylated BIM. Downregulation
      of BIM with the shRNA resulted in HCD57 cells more resistant to apoptosis induced
      by either EPO withdrawal or ERK inhibition. Although we observed no significant
      changes in the number of erythrocytes or reticulocytes in the circulation of Bim(
      /-) mice, erythroid progenitors from bone marrow in Bim(-/-) mice were reduced in
      number and more resistant to apoptosis induced by U0126 MEK/ERK inhibitor.
      CONCLUSION: EPO protects erythroid cells from apoptosis in part through ERK
      mediated phosphorylation followed by proteasomal degradation of BIM.

PMID- 19100676
TI  - Cathepsin W expressed exclusively in CD8+ T cells and NK cells, is secreted
      during target cell killing but is not essential for cytotoxicity in human CTLs.
AB  - OBJECTIVE: Cathepsin W (CatW, lymphopain) is a putative cysteine protease with
      restricted expression to natural killer (NK) cells and CD8(+) T cells and so far
      unknown function and properties. Here, we characterize in detail, the regulation
      of human CatW during T-cell development in response to different stimuli and its
      functional involvement in cytotoxic lymphocyte effector function. MATERIALS AND
      METHODS: Western blots and real time polymerase chain reaction of sorted,
      unstimulated, and stimulated cell subsets (thymocytes, T cells, NK cells) and
      their culture supernatants were used to study regulation and expression of CatW.
      Primary CD8(+) T cells and short-term T-cell lines were transfected with small
      interfering RNA to study the involvement of CatW in effector function such as
      target cell killing and interferon-gamma production. RESULTS: Levels of CatW
      expression correlate closely with cytotoxic capacity both during development and
      in response to factors influencing cytotoxicity. Furthermore, CatW is secreted
      during specific target cell killing. However, knockdown of CatW expression by
      small interfering RNA neither influences target cell killing nor interferon-gamma
      production. CONCLUSION: Despite being expressed in the effector subset of CD8(+)
      and NK cells and of being released during target cell killing, our functional
      inhibition studies exclude an essential role of CatW in the process of
      cytotoxicity.

PMID- 19100677
TI  - Low-dose busulphan conditioning and neonatal stem cell transplantation preserves
      vision and restores hematopoiesis in severe murine osteopetrosis.
AB  - OBJECTIVE: Infantile malignant osteopetrosis is a fatal disease caused by lack of
      functional osteoclasts. In most of patients, TCIRG1, encoding a subunit of a
      proton pump essential for bone resorption, is mutated. Osteopetrosis leads to
      bone marrow failure and blindness due to optic nerve compression. Oc/oc mice have
      a deletion in Tcirg1 and die around 3 to 4 weeks, but can be rescued by neonatal
      stem cell transplantation (SCT) after irradiation conditioning. However, as
      irradiation of neonatal mice results in retinal degeneration, we wanted to
      investigate whether conditioning with busulphan prior to SCT can lead to
      preservation of vision and reversal of osteopetrosis in the oc/oc mouse model.
      MATERIALS AND METHODS: Pregnant dams were conditioned with busulphan and their
      litters transplanted with 1 x 10(6) normal lineage-depleted bone marrow cells
      intravenously or intraperitoneally. Mice were followed in terms of survival and
      engraftment level, as well as with peripheral blood lineage analysis, bone and
      eye histopathology and a visual-tracking drum test to assess vision. RESULTS:
      Busulphan at 15 mg/kg was toxic to oc/oc mice. However, six of seven oc/oc mice
      conditioned with busulphan 7.5 mg/kg survived past the normal lifespan with 10%
      engraftment, correction of the skeletal phenotype, and normalization of
      peripheral blood lineages. Busulphan, in contrast to irradiation, did not have
      adverse effects on the retina as determined by histopathology, and 8 weeks after
      transplantation control and oc/oc mice retained their vision. CONCLUSION: Low
      dose busulphan conditioning and neonatal SCT leads to prolonged survival of oc/oc
      mice, reverses osteopetrosis and prevents blindness even at low engraftment
      levels.

PMID- 19100678
TI  - Combined BCR-ABL inhibition with lentiviral-delivered shRNA and dasatinib
      augments induction of apoptosis in Philadelphia-positive cells.
AB  - OBJECTIVE: This study investigated two approaches, short hairpin RNA (shRNA) and
      the potent ABL inhibitor, dasatinib, alone and together, to achieve complete
      inhibition of BCR-ABL activity in Philadelphia-positive (Ph(+)) cells. MATERIALS
      AND METHODS: shRNA specific for BCR-ABL b3a2 were delivered, by lentiviral
      transduction or electroporation, to K562 cells, with or without dasatinib. mRNA
      and protein knockdown were measured by quantitative reverse transcriptase
      polymerase chain reaction, flow cytometry, and Western blotting. BCR-ABL activity
      was assessed by intracellular flow cytometry for pCrkL. Cell death and apoptosis
      were assayed using trypan blue exclusion, Annexin-V, and active caspase-3
      staining. RESULTS: Forty-eight hours after transduction or electroporation of
      shRNA, BCR-ABL mRNA, and protein were reduced by 75% and >90%, respectively, and
      sustained for 5 days. Lentiviral delivery and electroporation were equally
      effective. pCrkL was inhibited in association with cell death. By 5 days after
      transduction or electroporation, viable cells represented 50% of input, with a 12
      fold reduction vs control, which expanded 6-fold. When shRNA, titrated by green
      fluorescent protein into low and high, was combined with dasatinib (concentration
      range, 0-10 nM), low shRNA was additive with low dasatinib (0.6 and 1 nM),
      leading to inhibition of pCrkL, induction of activated caspase-3, expression of
      Annexin-V, and marked reduction in viable cells. CONCLUSION: These results
      confirm that by lowering BCR-ABL levels with shRNA, complete inhibition of
      oncoprotein activity can be achieved with a lower concentration of dasatinib,
      thus providing a rationale for combining these approaches in the setting of high
      target expression, such as found in advanced phase disease and in the stem cell
      compartment.

PMID- 19100680
TI  - Acute peripheral nerve compression by a lipoma mimicking stroke.

PMID- 19100681
TI  - p53 controls prostate-derived factor/macrophage inhibitory cytokine/NSAID
      activated gene expression in response to cell density, DNA damage and hypoxia
      through diverse mechanisms.
AB  - The p53 tumor suppressor modulates cellular response to stress through both
      transcriptional and post-transcriptional mechanisms. Elucidation of the
      downstream targets of p53 following cell stress will aid in our understanding of
      the pathways involved in cellular adaptation to stressful stimuli. Here, we
      demonstrate that the TGF-beta superfamily member, and putative tumor suppressor,
      prostate-derived factor (PDF)/NSAID-activated gene (NAG)-1/macrophage inhibitory
      cytokine (MIC)-1 is induced in LNCaP human prostate cancer cells following
      treatment with the DNA-damaging agent, doxorubicin, culture under hypoxic
      conditions and by the hypoxia mimetic, cobalt chloride. Additionally, PDF
      expression was induced by increasing cell density. Expression of dominant
      negative p53 in LNCaP cells blocked induction of PDF mRNA and protein
      demonstrating the requirement for functional p53 in PDF induction by these
      stimuli. DNA damage and hypoxia resulted in increased p53 protein accumulation
      indicating that PDF expression may be controlled by cellular levels of p53. We
      also show the requirement for de novo protein synthesis in PDF induction by
      hypoxia and DNA damage. Increased PDF mRNA stability in response to hypoxia and
      cobalt chloride, but not doxorubicin, indicates that p53-dependent induction of
      PDF expression occurs via diverse mechanisms. Thus, PDF may represent a novel
      target of p53 in response to cell stress.

PMID- 19100679
TI  - A KIT juxtamembrane PY567 -directed pathway provides nonredundant signals for
      erythroid progenitor cell development and stress erythropoiesis.
AB  - OBJECTIVE: KITL/KIT can elicit diverse sets of signals within lymphoid, myeloid,
      mast, and erythroid lineages, and exert distinct effects on growth, survival,
      migration, adhesion, and secretory responses. Presently, we have applied a PY
      mutant allele knockin approach to specifically assess possible roles for KIT
      PY567 and KIT-PY719 sites, and coupled pathways, during erythropoiesis. MATERIALS
      AND METHODS: Mouse models used to investigate this problem include those
      harboring knocked-in KIT(Y567F/Y567F), KIT(Y569F/Y569F), KIT(Y719F,Y719F), and
      KIT(Y567F/Y567F:Y569F/Y569F) alleles. The erythron was stressed by
      myelosuppression using 5-fluorouracil, and by phenylhydrazine-induced hemolysis.
      In addition, optimized systems for ex vivo analyses of bone marrow and splenic
      erythropoiesis were employed to more directly analyze possible stage-specific
      effects on erythroid cell growth, survival, development and KIT signaling events.
      RESULTS: In Kit(Y567F/Y567F) mice, steady-state erythropoiesis was unperturbed
      while recovery from anemia due to 5-fluorouracil or phenylhydrazine was markedly
      impaired. Deficiencies in erythroid progenitor expansion occurred both in the
      bone marrow and the spleen. Responses to chronic erythropoietin dosing were also
      compromised. Ex vivo, Kit(Y567F/Y567F) (pro)erythroblast development was skewed
      from a Kit(pos)CD71(high) stage toward a subsequent Kit(neg)CD71(high)
      compartment. Proliferation and, to an extent, survival capacities were also
      compromised. Similar stage-specific defects existed for erythroid progenitors
      from Kit(Y567F/Y567F:Y569F/Y569F) but not KIT(Y719F/Y719F) mice. Kit(Y567F/Y567F)
      erythroblasts were used further to analyze KIT-PY567-dependent signals. MEK
      1,2/ERK-1,2 signaling was unaffected while AKT, p70S6K, and especially JNK2/p54
      pathways were selectively attenuated. CONCLUSIONS: Nonredundant KIT-PY567
      directed erythroblast-intrinsic signals are selectively critical for stress
      erythropoiesis. Investigations also add to an understanding of how KIT directs
      distinct outcomes among diverse progenitors and lineages.

PMID- 19100682
TI  - MET receptor tyrosine kinase as a therapeutic anticancer target.
AB  - Tyrosine kinases are frequently deregulated in cancer either by constitutive
      activation, mutation, or over-expression. Though they are often associated with
      an aggressive phenotype they are also proving to be a druggable target.
      Activation of the MET receptor tyrosine kinase promotes cell proliferation,
      scattering, invasion, survival, and angiogenesis. Deregulation of MET promotes
      tumor formation, growth, progression, metastasis, and therapeutic resistance.
      Because MET is a player in so many aspects of cancer development and progression,
      it is a strong candidate for targeted therapy. Numerous agents have been
      developed that are able to target MET expression and/or function and are the
      focus of this review.

PMID- 19100683
TI  - CLP induces apoptosis in human leukemia K562 cells through Ca(2+) regulating
      extracellular-related protein kinase ERK activation.
AB  - The cyclic lipopeptide (CLP) has been known to inhibit proliferation and induce
      apoptosis in cancer cells. However, the molecular mechanisms involved in CLP
      induced apoptosis are still uncharacterized in human leukemic K562 cells. The
      current study investigated the molecular mechanism of action of CLP, purified
      from Bacillus natto T-2. CLP-induced a sustained increase in concentration of
      intracellular Ca(2+). This increase in [Ca(2+)]i was associated with CLP-induced
      cell apoptosis and ERK phosphorylation. CLP-induced cell apoptosis was reversed
      by PD98059 (an inhibitor of ERK), but not by SB203580 (an inhibitor of p38) and
      SP200125 (an inhibitor of JNK), suggesting that the action of CLP on K562 cells
      was via ERK, but not via p38 and JNK. On the other hand, pretreatment with Bapta
      AM, a well-known calcium chelator, partially blocked CLP-induced apoptosis,
      indicating that the elevation of [Ca(2+)]i may play an important role in the
      apoptosis. Collectively, in K562 cells, CLP-induced an increase in [Ca(2+)]i
      which evoked ERK phosphorylation. This ERK phosphorylation subsequently activated
      Bax, cytochrome c and caspase-3 leading to apoptosis.

PMID- 19100684
TI  - Appraisal of potential environmental risks associated with human antibiotic
      consumption in Turkey.
AB  - A comprehensive analysis of Turkish antibiotic data was conducted to evaluate
      potential environmental risks associated with antibiotic consumption in Turkey
      for year 2007. Antibiotics were defined for systemic use or group J01 of the WHO
      Anatomical Therapeutic Chemical (ATC) classification system. Total emissions and
      prescriptions for each ATC group were classified separately into 17 different J01
      categories and three forms of medication (capsule/tablets, injectables and
      suspensions). Capsules and tablets were found as the most emitted form of
      medication in year 2007, with a total emission rate of about 585.5 tons/year
      (76%). Total antibiotic emission rates including all forms of medications were
      determined to be about 664.2 tons/year (86%) and 110.1 tons/year (14%) for adult
      and pediatric patients, respectively. An environmental risk assessment of 8 human
      antibiotics was conducted according to the EU draft guidance (CEC/III/5504/94,
      draft 6, version 4) and the risk was indicated by the ratio of predicted
      environmental concentration (PEC) to predicted no effect concentration (PNEC) for
      the aquatic environment. Available acute and chronic toxicity data were collected
      from the open peer-reviewed literature to derive PNEC. Risk quotients (PEC/PNEC)
      were then calculated for 8 pharmaceutical substances. PEC/PNEC ratio exceeded 1.0
      for beta-lactams (cephalosporins and penicillins), fluoroquinolones, macrolides
      and aminoglycosides. The findings of this study concluded that the release of
      these compounds from wastewater treatment plants may potentially be of an
      important environmental concern based on today's use of antibiotics in Turkey.

PMID- 19100685
TI  - Potential use of pyrite cinders as raw material in cement production: results of
      industrial scale trial operations.
AB  - Pyrite cinders, which are the waste products of sulphuric acid manufacturing
      plants, contain hazardous heavy metals with potential environmental risks for
      disposal. In this study, the potential use of pyrite cinders (PyCs) as iron
      source in the production of Portland cement clinker was demonstrated at the
      industrial scale. The chemical and mineralogical analyses of the PyC sample used
      in this study have revealed that it is essentially a suitable raw material for
      use as iron source since it contains >87% Fe(2)O(3) mainly in the form of
      hematite (Fe(2)O(3)) and magnetite (Fe(3)O(4)). The samples of the clinkers
      produced from PyC in the industrial scale trial operation of 6 months were tested
      for the conformity of their chemical composition and the physico-mechanical
      performance of the resultant cement products. The data were compared with the
      clinker products of the iron ore, which is used as the raw material for the
      production Portland cement clinker in the plant. The chemical compositions of all
      the clinker products of PyC appeared to conform to those of the iron ore clinker,
      and hence, a Portland cement clinker. The mechanical performance of the mortars
      prepared from the PyC clinker was found to be consistent with those of the
      industrial cements e.g. CEM I type cements. It can be inferred from the
      leachability tests (TCLP and SPLP) that PyC could be a potential source of heavy
      metal pollution while the mortar samples obtained from the PyC clinkers present
      no environmental problems. These findings suggest that the waste pyrite cinders
      can be readily used as iron source for the production of Portland cement. The
      availability of PyC in large quantities at low cost provides further significant
      benefits for the management/environmental practices of these wastes and for the
      reduction of mining and processing costs of cement raw materials.

PMID- 19100686
TI  - Pain in Parkinson's disease: Prevalence and characteristics.
AB  - Parkinson's disease is a chronic, progressive, incurable neurodegenerative
      disease. As the disease progresses, motor disturbances and non-motor symptoms
      represent considerable illness burdens. Symptom relief is the goal for the
      treatment. Pain is frequently observed in patients with Parkinson's disease, but
      its prevalence, characteristics and associations with Parkinson's disease are
      poorly documented. These were investigated in 176 home-living PD patients. They
      underwent a neurological examination and a structured interview for registration
      of pain characteristics in addition to responding to standardised questionnaires.
      Pain was reported by 146 (83%) patients. Compared to the general population, the
      Parkinson's disease patients experienced significantly more pain as measured by
      SF-36 Bodily Pain Scale. The average pain during the last 24h measured by the
      Brief Pain Inventory was 2.85. Fifty-three percent of the patients reported one,
      24% reported two and 5% reported three pain types. Musculoskeletal pain was
      reported by 70%, dystonic pain by 40%, radicular-neuropathic pain by 20% and
      central neuropathic pain by 10%. Thirty-four percent were on analgesic
      medication. Pain was not associated with age, disease duration or severity of the
      disease; female gender was the only significant predictor of pain. Pain is
      frequent and disabling, independent of demographic and clinical variables except
      for female gender, and is significantly more common in Parkinson's patients
      compared to the general population. A minority of the Parkinson's disease
      patients with pain received analgesic medication. The findings call for improved
      attention to assessment and treatment of pain in the follow-up of Parkinson's
      disease patients.

PMID- 19100687
TI  - Change is coming!

PMID- 19100688
TI  - Precipitation evolution in a Ti-free and Ti-containing stainless maraging steel.
AB  - Stainless maraging steels have a Cr content higher than 12wt% and show a
      excellent combination of high strength and ductility, which make them attractive
      for use in machinery fields and aircraft applications. The massive increase of
      strength during ageing treatment of maraging steels is related to a precipitation
      sequence of various nm-scaled intermetallic phases. The peak hardness especially
      in Ti-containing maraging steels can be reached after short-time ageing at
      temperatures around 500 degrees C. However, precipitation reactions in different
      stainless maraging steels are not fully understood, especially the evolution from
      clustering over growing to coarsening. In the present work a commercial maraging
      steel and a Ti-containing model alloy are investigated and compared to each
      other. The steels were isothermally heat treated at 525 degrees C for a range of
      times. Special emphasis was laid on the correlation of hardness to the formation
      and presence of different kinds of precipitates. The isothermal aged samples were
      investigated by using two advanced three-dimensional energy compensated atom
      probes (LEAP and 3DAP) both in voltage mode and in laser mode. The atom probe
      data were correlated to standard hardness measurements. The results show that the
      partial substitution of Al by Ti results in a different precipitation behaviour.
      While the Ti-free maraging steel exhibit only one type of precipitate, the Ti
      containing grade shows a change in the type of precipitates during ageing.
      However, this change leads to an accelerated coarsening and thus to a faster drop
      in hardness.

PMID- 19100689
TI  - Head and neck cancer in the elderly: an overview on the treatment modalities.
AB  - The percentage of elderly people with head and neck cancers (HNC) is rising due
      to increasing average lifespan. As with younger patients, elderly patients
      require a multidisciplinary approach in order to optimise treatment results. The
      biological, not the chronological, age should be defined individually based on co
      morbidities and performance status. A comprehensive geriatric assessment
      represents the first and essential step for selecting further treatment options.
      Major improvements have been accomplished in surgical techniques and radiotherapy
      delivery. Several chemotherapeutic agents and targeted therapies with different
      toxicity profile are also available. However, the randomised studies that defined
      the nature of these improvements included only a small proportion of patients
      older than 65 years. In deciding which treatment strategy would be suitable for
      an individual elderly patient, we review the literature regarding surgery,
      radiotherapy, and chemotherapy or their various combinations.

PMID- 19100690
TI  - Effect of low density lipoprotein on the quality of cryopreserved dog semen.
AB  - Egg yolk is included in extenders for semen cryopreservation due to its
      protective effect against cold shock, which is attributed to the presence of low
      density lipoprotein (LDL). This study evaluates how semen quality is affected by
      using LDL as a replacement for egg yolk in extenders for cooled and frozen dog
      semen. In Experiment 1, semen was extended in TRIS-glucose at 5 degrees C, in
      four treatments: 20% egg yolk (T1); 6% (T2); 8% (T3); and 10% LDL (T4). Sperm
      motility and membrane integrity after 24, 48, 72 and 96 h and the 50%
      conservation rate of motile spermatozoa (50 M) were evaluated. The 50 M was less
      for T1 than for the other treatments (P<0.01), but T2-T4 did not differ (P>0.05).
      In Experiment 2, glycerol at 10% was included in the freezing extender, in
      treatments similar to those from Experiment 1. Sperm motility and membrane
      integrity did not differ for T2, T3 and T4 at any period in Experiment 1 and
      after thawing in Experiment 2 (P>0.05), but were greater for all LDL treatments
      than for T1 (P<0.01), in both experiments. Thus, LDL can replace egg yolk in the
      composition of the TRIS-glucose extender for cooled or frozen dog semen.

PMID- 19100692
TI  - Comparison of efficiency between two artificial insemination methods using frozen
      thawed semen in domestic cat (Felis catus): artificial insemination in domestic
      cats.
AB  - The aim of this study was to compare the efficiency of the intravaginal (IVAI)
      vs. intrauterine artificial insemination (IUAI) using frozen-thawed sperm in the
      domestic cat. Semen was collected from two tom cats using an artificial vagina
      and samples were assessed for motility (computer-assisted sperm analysis (CASA)),
      sperm morphology and plasma membrane integrity. After dilution with TRIS/OEP/YOLK
      (4% of glycerol), sperm samples were loaded into 0.25 mL straws (25 x 10(6)motile
      sperm/straw), incubated at 5 degrees C for 20 min and cryopreserved over liquid
      nitrogen (LN(2)) vapor for 15 min and then immersed in LN(2). For each AI, four
      straws from the same male were thawed (12s at 46 degrees C) and centrifuged at
      250 x g for 8 min to pellet the sperm. The supernatant was discarded and sperm
      pellet resuspended with the remaining liquid, approximately 100 microL, and
      analyzed as described above. Queens were treated with a single im injection of
      100 IU eCG to induce ovarian follicular development. Final oocyte maturation and
      ovulation was induced with 100 IU hCG given im at 82-84 h after eCG
      administration. Thirty hours after hCG administration, females were inseminated
      either intrauterine (n=8 queens) or intravaginally (n=8 queens), using thawed
      sperm from a single male. Although a pronounced decrease in sperm motility,
      acrosome and plasma membrane integrity was observed in sperm samples from both
      cats, a pregnancy rate of 75% was achieved when using the intrauterine AI method
      compared with 0% pregnancy when inseminated intravaginally.

PMID- 19100691
TI  - Leptin accelerates pronuclear formation following intracytoplasmic sperm
      injection of porcine oocytes: Possible role for MAP kinase inactivation.
AB  - Leptin, a multifunctional hormone, is present in mammalian oocytes and follicular
      fluids and cumulus cells. While leptin modulates oocyte maturation in vitro which
      seems to result in enhancement of embryo development, it is unclear whether
      leptin treatment of oocytes affects cytoplasmic maturation and fertilization
      processes. In order to gain a better understanding of the role of leptin during
      oocyte maturation, we examined microtubule and microfilament assembly following
      oocyte maturation and blastocyst formation, mitogen-activated protein kinase
      (MAPK) activity, and pronuclear formation following parthenogenetic stimuli or
      intracytoplasmic sperm injection (ICSI) in leptin-treated oocytes. Addition of 10
      or 100 ng/ml leptin during oocyte maturation did not increase the proportion of
      metaphase II oocytes, but enhanced development to blastocyst stage by day 7
      (P<0.01) after parthenogenetic activation (PA), accompanied by increased cell
      number. However there was no effect on the number of apoptotic cells in
      blastocysts. Following maturation in the presence of leptin, there were more
      oocytes with normal spindle formation. MAPK activity decreased more rapidly, and
      pronuclear formation was accelerated after parthenogenetic activation or ICSI of
      leptin-treated oocytes. These results suggested that exogeneous leptin enhanced
      spindle assembly and accelerated pronuclear formation following fertilization,
      possibly via the MAPK pathway.

PMID- 19100693
TI  - Quality of life in women with postmenopausal osteoporosis: correlation between
      QUALEFFO 41 and SF-36.
AB  - OBJECTIVE: To evaluate quality of life (QoL) in women with postmenopausal
      osteoporosis, correlating the QUALEFFO 41 with the short-form health survey 36
      (SF-36) and evaluated some factors that can influenced the QoL of women with
      osteoporosis. METHODS: A cross-sectional study was conducted in 220
      postmenopausal women (ages ranging from 55 to 80 years). Of the total number, 110
      women had osteoporosis and 110 women did not have osteoporosis and these women
      were age-matched (+/-3 years). Two questionnaires were administered to all
      subjects for evaluation of QoL: the quality of life questionnaire of the European
      foundation for Osteoporosis 41 (QUALEFFO 41) and the short-form health survey 36
      (SF-36). For data analysis, a significance level of 5% was set (p<0.05). RESULTS:
      Clinical characteristics between the groups were similar, with statistically
      significant differences only in body mass index (BMI), race, school education,
      age at menopause and use of hormone therapy (HT) (p<0.001). Women with
      osteoporosis had a worse QoL both in the QUALEFFO 41 and in the SF-36, in all
      domains studied. Data was adjusted for BMI, race, school education and use of HT
      (p<0.001). There was a significant correlation between all domains in the
      QUALEFFO 41 questionnaire and their corresponding domains in the SF-36 (p<0.001).
      The only factors related to worse QoL were BMI>25 and sedentary lifestyle. In
      contrast, paid work was associated with a better QoL (CI=95%). CONCLUSION: Women
      with osteoporosis had an impaired QoL, especially relating to the physical,
      psychological and social aspects. The factors associated with QoL were obesity,
      sedentary lifestyle and paid work.

PMID- 19100694
TI  - A prescription for human immunology.
AB  - Inbred mice have been an extremely successful tool for basic immunology, but much
      less so as models of disease. Thus, to maximize the use of immunologic approaches
      to improve human health, we need more strategically directed efforts in human
      immunology. This would also open up new opportunities for basic research.

PMID- 19100695
TI  - Alternative splicing of CD45: the tip of the iceberg.
AB  - Mechanisms underlying the regulated splicing of CD45 RNA have been long-standing
      puzzles. In this issue of Immunity, Wu et al. (2008) identify hnRNPLL as a
      critical regulator of both signal-induced exon skipping in CD45 and global
      alternative-transcript expression in memory T cells.

PMID- 19100697
TI  - CD44 keeps tumor killers polarized.
AB  - In this issue of Immunity, Mrass et al. (2008) report that CD44 critically
      contributes to the stabilization of polarity in migrating cytotoxic T lymphocytes
      by anchoring cytoskeletal proteins to the cell membrane at their uropods.

PMID- 19100696
TI  - Keeping autoimmunity in check: how to control a Th17 cell controller.
AB  - The transcription factor IRF-4 is necessary for Th17 cell differentiation. In
      this issue of Immunity, Chen et al. (2008) show that IRF-4-binding protein is a
      critical negative regulator of IRF-4 function, regulating production of the
      cytokines IL-21 and IL-17.

PMID- 19100698
TI  - Elite suppression of HIV-1 replication.
AB  - Rare HIV-1-infected individuals are able to control viral replication without
      antiretroviral therapy. In this issue of Immunity, Migueles et al. (2008) show
      that HIV-1-specific CD8+ T cells from these individuals effectively suppress
      viral replication by granzyme B-mediated killing of target cells.

PMID- 19100699
TI  - Homeostasis of naive and memory T cells.
AB  - The peripheral mature T cell pool is regulated by complex homeostatic mechanisms.
      Naive T cells are maintained by interleukin-7 (IL-7) and T cell receptor (TCR)
      signaling from contact with major histocompatibility complex (MHC), which sustain
      expression of antiapoptotic molecules and allow the cells to survive in
      interphase. Competition for these ligands declines when T cell numbers are
      reduced and causes residual naive T cells to proliferate and differentiate into
      memory-like cells. This memory cell population is thus heterogeneous and
      comprised of cells derived from responses to both foreign and self-antigens.
      Typical memory cells are kept alive and induced to divide intermittently by a
      mixture of IL-7 and IL-15. This review highlights recent advances in how naive
      and memory T cell homeostasis is regulated.

PMID- 19100700
TI  - Memory T cell RNA rearrangement programmed by heterogeneous nuclear
      ribonucleoprotein hnRNPLL.
AB  - Differentiation of memory cells involves DNA-sequence changes in B lymphocytes
      but is less clearly defined in T cells. RNA rearrangement is identified here as a
      key event in memory T cell differentiation by analysis of a mouse mutation that
      altered the proportions of naive and memory T cells and crippled the process of
      Ptprc exon silencing needed to generate CD45RO in memory T cells. A single
      substitution in a memory-induced RNA-binding protein, hnRNPLL, destabilized an
      RNA-recognition domain that bound with micromolar affinity to RNA containing the
      Ptprc exon-silencing sequence. Hnrpll mutation selectively diminished T cell
      accumulation in peripheral lymphoid tissues but not proliferation. Exon-array
      analysis of Hnrpll mutant naive and memory T cells revealed an extensive program
      of alternative mRNA splicing in memory T cells, coordinated by hnRNPLL. A
      remarkable overlap with alternative splicing in neural tissues may reflect a co
      opted strategy for diversifying memory T cells.

PMID- 19100701
TI  - Innate and adaptive interleukin-22 protects mice from inflammatory bowel disease.
AB  - Inflammatory bowel disease (IBD) is a chronic inflammatory disease thought to be
      mediated by dysfunctional innate and/or adaptive immunity. This aberrant immune
      response leads to the secretion of harmful cytokines that destroy the epithelium
      of the gastrointestinal tract and thus cause further inflammation. Interleukin-22
      (IL-22) is a T helper 17 (Th17) T cell-associated cytokine that is bifunctional
      in that it has both proinflammatory and protective effects on tissues depending
      on the inflammatory context. We show herein that IL-22 protected mice from IBD.
      Interestingly, not only was this protection mediated by CD4+ T cells, but IL-22
      expressing natural killer (NK) cells also conferred protection. In addition, IL
      22 expression was differentially regulated between NK cell subsets. Thus, both
      the innate and adaptive immune responses have developed protective mechanisms to
      counteract the damaging effects of inflammation on tissues.

PMID- 19100702
TI  - CD44 mediates successful interstitial navigation by killer T cells and enables
      efficient antitumor immunity.
AB  - Although T lymphocytes are constitutively nonadherent cells, they undergo
      facultative polarity during migration and upon interaction with cells presenting
      cognate antigen, suggesting that cell polarity might be critical for target cell
      destruction. Using two-photon imaging of tumor-infiltrating T lymphocytes, we
      found that CD44, a receptor for extracellular matrix proteins and
      glycosaminoglycans, was crucial for interstitial T cell navigation and,
      consequently, efficient tumor cell screening. CD44 functioned as a critical
      regulator of intratumoral movement by stabilizing cell polarity in migrating T
      cells, but not during target cell interactions. Stable anterior-posterior
      asymmetry was maintained by CD44 independently of its extracellular domain.
      Instead, migratory polarity depended on the recruitment of ezrin, radixin, moesin
      (ERM) proteins by the intracellular domain of CD44 to the posterior cellular
      protrusion. Our results formally demonstrate that CD44-dependent T lymphocyte
      locomotion within target sites represents an essential immunologic checkpoint
      that determines the potency of T cell effector functions.

PMID- 19100703
TI  - Lymphotoxin-dependent prion replication in inflammatory stromal cells of
      granulomas.
AB  - Prior to invading the nervous system, prions frequently colonize lymphoid organs
      and sites of inflammatory lymphoneogenesis, where they colocalize with Mfge8+
      follicular dendritic cells (FDCs). Here, we report that soft-tissue granulomas, a
      frequent feature of chronic inflammation, expressed the cellular prion protein
      (PrPC, encoded by Prnp) and the lymphotoxin receptor (LTbetaR), even though they
      lacked FDCs and did not display lymphoneogenesis. After intraperitoneal prion
      inoculation, granulomas of Prnp(+/+) mice, but not Prnp(-/-) granulomas or
      unaffected Prnp(+/+) skin, accumulated prion infectivity and disease-associated
      prion protein. Bone-marrow transfers between Prnp(+/+) and Prnp(-/-) mice and
      administration of lymphotoxin signaling antagonists indicated that prion
      replication required radioresistant PrPC-expressing cells and LTbetaR signaling.
      Granulomatous PrPC was mainly expressed by stromal LTbetaR+ mesenchymal cells
      that were absent from unaffected subcutis. Hence, granulomas can act as
      clinically silent reservoirs of prion infectivity. Furthermore, lymphotoxin
      dependent prion replication can occur in inflammatory stromal cells that are
      distinct from FDCs.

PMID- 19100704
TI  - Photostabilization of Bacillus thuringiensis fermented wastewater and wastewater
      sludge based biopesticides using additives.
AB  - Photoprotection (against UV-A and UV-B radiations) of the active components of
      Bacillus thuringiensis var. kurstaki obtained from the fermentation of various
      culture media was investigated. The culture media comprised: starch industry
      wastewater; secondary wastewater sludge (non-hydrolyzed and hydrolyzed) and soya
      (used as a reference). Photoprotection was carried out by using various UV
      protection additives, namely, para-aminobenzoic acid, lignosulfonic acid and
      molasses at different concentrations (0.1%, 0.15% and 0.2%, w/w). In the absence
      of UV-protection agents, secondary sludge demonstrated natural UV protection with
      half-lives ranging from 3.25 to 3.4 d. The half-life for soya and starch industry
      wastewater was 1.9 and 1.8 d, respectively. Para-amino-benzoic acid as a UV
      protection agent at 0.20% (w/w) gave excellent UV-protection for soya and starch
      industry wastewater with half-lives being 5.9 and 7 d, respectively. Likewise,
      lignosulfonic acid at 0.20% (w/w) was an effective photostabilizer for hydrolyzed
      and non-hydrolyzed secondary sludge with half-lives of 7.25 and 8 d,
      respectively. Hence, when similar concentration of the UV-protection additives
      was used, photoprotection was higher for the alternative media than the
      conventional soya medium, validating the technical feasibility of using three
      additives.

PMID- 19100705
TI  - Multiplex single nucleotide polymorphisms genotyping using solid-phase single
      base extension on magnetic nanoparticles.
AB  - To fulfill the increasing need for large-scale genetic research, we have
      developed a new solid-phase single base extension (SBE) protocol on magnetic
      nanoparticles (MNPs) for multiplex SNP detection using adapter polymerase chain
      reaction (PCR) products as templates. Extension primers were covalently
      immobilized on the MNPs, and allele-specific extension took place along the
      stretch of target DNA for one-color ddNTP incorporation. The MNPs with
      fluorophores were spotted on a glass slide to fabricate a "bead array" to
      discriminate their genotypes. Eight SNP loci of three DNA samples were
      interrogated, and the experiment demonstrated that it is an efficient method for
      large-scale SNP genotyping.

PMID- 19100706
TI  - Quantitation of full-size small interfering RNA by tailing with terminal
      deoxynucleotidyl transferase and reverse transcription-polymerase chain reaction
      analysis.
AB  - Accurate estimation of small interfering RNA (siRNA) concentration in cells and
      blood is increasingly important for pharmacokinetic studies required to develop
      siRNA drugs. We report a method that detects siRNA having 3'-terminal
      deoxynucleotide overhangs, such as 3'-dTdT, present in most chemically
      synthesized siRNAs. Short overhangs were elongated to oligo-dG by incubation with
      terminal deoxynucleotidyl transferase and dGTP and were used as priming sites for
      reverse transcription of siRNA to complementary DNA (cDNA). The resultant cDNA
      was used as a template for quantitation by polymerase chain reaction. This method
      was reliable for determining the pharmacokinetics of siRNA in blood of injected
      mice.

PMID- 19100707
TI  - Amperometric sensor based on ferrocene-modified multiwalled carbon nanotube
      nanocomposites as electron mediator for the determination of glucose.
AB  - A kind of nanocomposite with good dispersion in water was prepared through
      covalent adsorption of ferrocenecarboxaldehyde on multiwalled carbon nanotubes
      (MWNTs) for electrical communication between glucose oxidase (GOD) and electrode.
      The ferrocene-modified multiwalled carbon nanotube nanocomposites (MWNTs-Fc)
      could be conveniently cast on electrode surfaces. With the aid of chitosan, GOD
      was then immobilized on the nanostructure film to form a reagentless amperometric
      sensor for glucose determination. FTIR spectra and cyclic voltammetry were used
      to characterize the nanocomposites. The presence of both ferrocene as mediator of
      electron transfer and MWNTs as conductor enhanced greatly the enzymatic response
      to the oxidation of glucose. The novel biosensor exhibited a fast response toward
      glucose with a detection limit of 3.0 x 10(-6) mol/L and the linear range
      extended up to 3.8 x 10(-3) mol/L.

PMID- 19100708
TI  - Protein fractionation according to molecular size in constant pH media with
      immobilized charges in colinear porosity gradient.
AB  - A new method of protein electrophoresis is described here. Electrophoretic
      separation is performed in gel media with uniform concentration of immobilized
      charges, combined with porosity gradient directed against protein movement.
      Successful separation becomes possible due to the effect of strong sample zone
      compression; the latter effect is connected with complex conductivity profile
      dynamics in a gel system containing immobilized charges. Immobilized buffers
      combined with porosity gradient provide an opportunity of protein discrimination
      based on molecular size, while in the case of uniform gel concentration the
      separation is based on mobility differences and strongly affected by non-uniform
      electric field strength profile. The proposed method does not require ionic
      detergent for protein separation according to their molecular weight.

PMID- 19100709
TI  - Measurements of mitochondrial calcium in vivo.
AB  - Mitochondria play a pivotal role in intracellular Ca(2+) signalling by taking up
      and releasing the ion upon specific conditions. In order to do so, mitochondria
      depend on a number of factors, such as the mitochondrial membrane potential and
      spatio-temporal constraints. Whereas most of the basic principles underlying
      mitochondrial Ca(2+) handling have been successfully deciphered over the last 50
      years using assays based on in vitro preparations of mitochondria or cultured
      cells, we have only just started to understand the actual physiological relevance
      of these processes in the whole animal. Recent advancements in imaging and
      genetically encoded sensor technologies have allowed us to visualise
      mitochondrial Ca(2+) transients in live mice. These studies used either two
      photon microscopy or bioluminescence imaging of cameleon or aequorin-GFP Ca(2+)
      sensors, respectively. Both methods revealed a consistent picture of Ca(2+)
      uptake into mitochondria under physiological conditions even during very short
      lasting elevations of cytosolic Ca(2+) levels. The big future challenge is to
      understand the functional impact of such Ca(2+) signals on the physiology of the
      observed tissue as well as of the whole organism. To that end, the development of
      multiparametric in vivo approaches will be mandatory.

PMID- 19100710
TI  - Glucocorticoid receptors and other nuclear transcription factors in mitochondria
      and possible functions.
AB  - The central role of mitochondria in basic physiological processes has rendered
      this organelle a receiver and integrator of multiple regulatory signals. Steroid
      and thyroid hormones are major modulators of mitochondrial functions and the
      question arises as to how these molecules act at the molecular level. The
      detection in mitochondria of steroid and thyroid hormone receptors suggested
      their direct action on mitochondrial functions within the context of the
      organelle. The interaction of the receptors with regulatory elements of the
      mitochondrial genome and the activation of gene transcription underlies the
      hormonal stimulation of energy yield. Glucocorticoid activation of hepatocyte RNA
      synthesis is one of the experimental models exploited in this respect.
      Furthermore, the interaction of the receptors with apoptotic/antiapoptotic
      factors is possibly associated with the survival-death effects of the hormones.
      In addition to the steroid/thyroid hormone receptors, several other receptors
      belonging to the superfamily of nuclear receptors, as well as transcription
      factors with well defined nuclear actions, have been found in mitochondria. How
      these molecules act and interact and how they can affect the broad spectrum of
      mitochondrial functions is an emerging exciting field.

PMID- 19100711
TI  - Lipid binding properties of 4E10, 2F5, and WR304 monoclonal antibodies that
      neutralize HIV-1.
AB  - Two human mAbs (2F5 and 4E10), originally derived from HIV-1-infected patients,
      are important, but rare, mAbs that exhibit broad cross-clade neutralizing
      activities against HIV-1. In addition to peptide sequences on the gp41 envelope
      protein, both antibodies reportedly also bound specifically to several
      phospholipid antigens. However, the phospholipid binding property of 2F5 has been
      disputed and, because of uncertainly regarding phospholipid binding, the modeling
      of neutralizing mechanisms has been difficult. To explore this issue, we examined
      the binding of 4E10 and 2F5 to a broad range of lipid antigens by ELISA. 4E10 and
      2F5 both bound to a variety of purified phospholipids, and 4E10 bound, but 2F5
      did not bind, to cardiolipin. Both mAbs also bound to a sulfated glycolipid,
      sulfogalactosyl ceramide (sulfatide), and to two neutral glycolipids, galactosyl
      ceramide and glucosyl ceramide, but not to other galactosyl glycolipids. 4E10,
      but not 2F5, also bound to cholesterol, although both mAbs bound to squalene.
      Interestingly, 4E10, but not 2F5, exhibited striking binding to lipid A, the
      lipid moiety of Gram-negative bacterial lipopolysaccharide. The binding
      properties of 4E10 to phospholipids, sulfatide, cholesterol, squalene, and lipid
      A were similar to those of a neutralizing murine mAb (WR304) induced by liposomes
      containing phosphatidylinositol phosphate and lipid A, although WR304 did not
      bind to neutral glycolipids. The discovery of a binding specificity of 4E10 for
      lipid A, a widely used vaccine adjuvant, suggests that innate immunity stimulated
      by lipid A could have played a role for induction of multispecific antibodies
      that simultaneously recognize both HIV-1 protein and lipid antigens.

PMID- 19100712
TI  - Probing molecular level interaction of oseltamivir with H5N1-NA and model
      membranes by molecular docking, multinuclear NMR and DSC methods.
AB  - Structure-based drug design has led to the introduction of three drugs-
      oseltamivir (GS-4104), zanamivir (GG-167) and peramivir (RWJ-270201) which target
      the enzyme neuraminidase, for treatment of influenza infections. Using
      comparative docking studies we propose that more potent molecules against
      neuraminidase can be obtained by appending extra positively charged substituents
      at the C5 position of the oseltamivir skeleton. This provides an additional
      interaction with the enzyme and may overcome the problem of resistance
      encountered with these drugs. To get an insight into the transport and absorption
      of oseltamivir--the ethyl ester prodrug (GS-4104) as well as its mechanism of
      action, we have carried out 1H, 13C, 31P NMR, DSC and TEM studies on GS-4104 with
      model membranes prepared from DMPC/DPPC/POPC. These studies reveal that
      interactions between GS-4104 and the membrane are both electrostatic (involving H
      bonding) and hydrophobic (involving the hydrophobic chain and cyclohexene ring of
      GS-4104) in nature. The prodrug is seen to increase the fluidity as well as
      stabilize the bilayer phase of the membrane. This property may be responsible for
      preventing viral entry into the cells by preventing fusion of the virus outer
      coat with the cell membrane.

PMID- 19100713
TI  - Generation and characterization of cells that can be conditionally depleted of
      mitochondrial SOD2.
AB  - Manganese-dependent superoxide dismutase (SOD2) serves as the primary defense
      against mitochondrial superoxide, and decreased SOD2 activity results in a range
      of pathologies. To investigate the events occurring soon after depletion of SOD2,
      we generated SOD2 gene knockout chicken DT40 cells complemented with a human SOD2
      (hSOD2) cDNA, whose expression can be switched off by doxycycline (Dox). When
      SOD2 was depleted by the addition of Dox, the cells grew slightly slower and
      formed fewer colonies than cells expressing hSOD2. In addition, these cells
      showed a high sensitivity to paraquat, which produces superoxide, and died
      through apoptosis. In contrast to results obtained with mouse and DrosophilaSod2
      mutants, we found no indication of an increase in DNA lesions due to depletion of
      SOD2.

PMID- 19100714
TI  - Upregulation of fibroblast growth factor-2 by visfatin that promotes endothelial
      angiogenesis.
AB  - Adipokines have been known to act as angiogenic regulators in the process of
      angiogenesis. Recently, we have demonstrated that visfatin, a novel adipokine,
      has angiogenic activity. However, little has been reported on the underlying
      mechanism of visfatin-induced angiogenesis. In this study, we report that
      visfatin-induced angiogenesis is mediated by endothelial fibroblast growth factor
      2 (FGF-2). Visfatin increased the levels of FGF-2 mRNA and protein in human
      endothelial cells. The enhancement in FGF-2 expression was prevented by an
      inhibitor of the extracellular signal-regulated kinase 1/2 (Erk1/2) pathway.
      Furthermore, visfatin-induced angiogenesis was reduced by inhibition of FGF-2
      receptor kinase or by neutralization of FGF-2 function. Taken together, our
      results indicate that visfatin-induced endothelial angiogenesis is composed
      largely of two sequential steps: the induction of Erk1/2-dependent FGF-2 gene
      expression by visfatin and the subsequent FGF-2-induced angiogenesis. These data
      further suggest an integral role for visfatin-FGF-2 signaling axis in modulating
      endothelial angiogenesis.

PMID- 19100715
TI  - Effect of dietary calcium and 1,25-(OH)2D3 on the expression of calcium transport
      genes in calbindin-D9k and -D28k double knockout mice.
AB  - The phenotypes of calbindin-D9k (CaBP-9k) and -28k (CaBP-28k) single knockout
      (KO) mice are similar to wild-type (WT) mice due to the compensatory action of
      other calcium transport proteins. In this study, we generated CaBP-9k/CaBP-28k
      double knockout (DKO) mice in order to investigate the importance of CaBP-9k and
      CaBP-28k in active calcium processing. Under normal dietary conditions, DKO mice
      did not exhibit any changes in phenotype or the expression of active calcium
      transport genes as compared to WT or CaBP-28k KO mice. Under calcium-deficient
      dietary conditions, the phenotype and expression of calcium transport genes in
      CaBP-28k KO mice were similar to WT, whereas in DKO mice, serum calcium levels
      and bone length were decreased. The intestinal and renal expression of transient
      receptor potential vanilloid member 6 (TRPV6) mRNA was significantly decreased in
      DKO mice fed a calcium-deficient diet as compared to CaBP-28k KO or WT mice, and
      DKO mice died after 4 weeks on a calcium-deficient diet. Body weight, bone
      mineral density (BMD) and bone length were significantly reduced in all mice fed
      a calcium and 1,25-(OH)(2)D(3)-deficient diet, as compared to a normal diet, and
      none of the mice survived more than 4 weeks. These results indicate that deletion
      of CaBP-28k alone does not affect body calcium homeostasis, but that deletion of
      CaBP-9k and CaBP-28k has a significant effect on calcium processing under calcium
      deficient conditions, confirming the importance of dietary calcium and 1,25
      (OH)(2)D(3) during growth and development.

PMID- 19100716
TI  - Assembled capsules transportation driven by motor proteins.
AB  - An active biomimetic system by integrating kinesin motor, microtubule, and man
      made biomimetic microcapsule has been constructed. Biomimetic microcapsules were
      fabricated by using the layer-by-layer technique and could serve as cargos in
      this active biomimetic system. Both of the hollow and filled capsules as cargos
      can be transported by kinesin motors along microtubules. It may help to create
      kinesin-powered complex hybrid micro- and nanodevices.

PMID- 19100717
TI  - First in-gel detection and purification of human xylosyltransferase II.
AB  - Human xylosyltransferases I and II (XylT-I, XylT-II) are key enzymes in
      glycosaminoglycan biosynthesis. Knowledge about the in vivo molecular weight,
      oligomeric state or turnover number are essential characteristics which have been
      addressed in this study. XylT-II was purified from Pichia pastoris by
      fractionated ammonium sulfate precipitation, heparin affinity and ion exchange
      chromatography. XylT-II was purified over 7000-fold with a final yield of 2.6%.
      By utilizing mass spectra analysis we can prove its first in-gel detection
      showing a migration pattern behavior that confirms its in silico molecular weight
      of 95.8 kDa. We could determine a turnover number of 2.18 min(-1) or one
      transferred xylose molecule per one XylT-II molecule each 27.5s. The k(cat)/K(M)
      ratio was 0.357 min(-1)microM(-1) for XylT-II using the bikunin-homologous
      acceptor Bio-QEEEGSGGGQKK-F. The comparison to XylT-I derived from the same
      organism revealed a 2.4-fold higher catalytic efficiency (0.870 min(-1)microM(
      1)) for XylT-I.

PMID- 19100718
TI  - Long-term resveratrol administration reduces metabolic disturbances and lowers
      blood pressure in obese Zucker rats.
AB  - Resveratrol is a natural polyphenolic stilbene derivative found in several human
      diet components that possess important and wide-ranging effects in biological
      systems including anticancer, anti-inflammatory, antioxidant, cardio-protective,
      and anti-ageing actions and beneficial properties against metabolic diseases.
      This study addresses the effects of long-term administration of resveratrol on
      several functional alterations arising from the metabolic syndrome experimental
      model of obese Zucker rats, and the possible mechanisms involved. The high plasma
      concentrations of triglycerides, total cholesterol, free fatty acids, insulin and
      leptin found in obese Zucker rats were reduced in obese rats that received
      resveratrol. Furthermore, the elevated hepatic lipid content was significantly
      lower in obese rats treated with resveratrol, an effect which was related to the
      increased phosphorylation of 5'-AMP-activated protein kinase (AMPK) and acetyl
      CoA carboxylase (ACC) in the liver of these animals. Resveratrol treatment also
      improved the inflammatory status peculiar to this model, as it increased the
      concentration of adiponectin and lowered tumor necrosis factor-alpha production
      in the visceral adipose tissue (VAT) of obese Zucker rats. Moreover, chronic
      intake of resveratrol enhanced VAT eNOS expression among obese Zucker rats. These
      effects parallel the activation of AMPK and inhibition by phosphorylation of ACC
      in this tissue. The raised systolic blood pressure and reduced aortic eNOS
      expression found in obese Zucker rats were significantly improved in the
      resveratrol-treated obese rats. In conclusion, resveratrol improved dyslipidemia,
      hyperinsulinemia, hyperleptinemia and hypertension in obese Zucker rats, and
      produced anti-inflammatory effects in VAT, effects that seem to be mediated by
      AMPK activation.

PMID- 19100719
TI  - SJ23B, a jatrophane diterpene activates classical PKCs and displays strong
      activity against HIV in vitro.
AB  - Existence of virus reservoirs makes the eradication of HIV infection extremely
      difficult. Current drug therapies neither eliminate these viral reservoirs nor
      prevent their formation. Consequently, new strategies are needed to target these
      reservoirs with the aim of decreasing their size. We analysed a series of
      jatrophane diterpenes isolated from Euphorbia hyberna and we found that one of
      them, SJ23B, induces the internalization of the HIV-1 receptors CD4, CXCR4 and
      CCR5 and prevents R5 and X4 viral infection in human primary T cells at the
      nanomolar range. Moreover, SJ23B is a potent antagonist of HIV-1 latency. Using
      Jurkat-LAT-GFP cells, a model for HIV-1 latency, we found that prostratin and
      SJ23B activate HIV-1 gene expression, with SJ23B being at least 10-fold more
      potent than prostratin. SJ23B did not elicit transforming foci activity in NIH
      3T3 cells but is a potent activator of PKCalpha and delta as measured by in vitro
      kinase assays and by cellular translocation experiments. By using isoform
      specific PKC inhibitors we found that cPKCs are critical for SJ23B-induced HIV-1
      reactivation. We also showed that both SJ23B-induced IkappaBalpha degradation and
      NF-kappaB activation were inhibited by the classical PKC inhibitor, Go6976.
      Accordingly, SJ23B synergizes with ionomycin to translocate PKCalpha to the
      plasma membrane and to activate the NF-kappaB pathway. Moreover, SJ23B activates
      both NF-kappaB and Sp1-dependent transcriptional activities in primary T cells.
      We have shown that diterpene jatrophanes represent a new member of anti-AIDS
      agents that could be developed for mitigating HIV reactivation.

PMID- 19100720
TI  - Cooperation between Apo2L/TRAIL and bortezomib in multiple myeloma apoptosis.
AB  - The proteasome inhibitor bortezomib is currently an important drug for treatment
      of relapsed and refractory multiple myeloma (MM) and for elderly patients.
      However, cells from some patients show resistance to bortezomib. We have
      evaluated the possibility of improving bortezomib therapy with Apo2L/TRAIL, a
      death ligand that induces apoptosis in MM but not in normal cells. Results
      indicate that cotreatment with low doses of bortezomib significantly increased
      apoptosis of MM cells showing partial sensitivity to Apo2L/TRAIL. Bortezomib
      treatment did not significantly alter plasma membrane amount of DR4 and DR5 but
      increased Apo2L/TRAIL-induced caspase-8 and caspase-3 activation. Apo2L/TRAIL
      reverted bortezomib-induced up-regulation of beta-catenin, Mcl-1 and FLIP,
      associated with the enhanced cytotoxicity of combined treatment. More important,
      some cell lines displaying resistance to bortezomib were sensitive to Apo2L/TRAIL
      induced apoptosis. A cell line made resistant by continuous culture of RPMI 8226
      cells in the presence of bortezomib (8226/7B) was highly sensitive to Apo2L/TRAIL
      induced apoptosis. Moreover, RPMI 8226 cells overexpressing Mcl-1 (8226/Mcl-1) or
      Bcl-x(L) (8226/Bcl-x(L)) also showed enhanced resistance to bortezomib, but co
      treatment with Apo2L/TRAIL reverted this resistance. These results indicate that
      Apo2L/TRAIL can cooperate with bortezomib to induce apoptosis in myeloma cells
      and can be an useful adjunct for MM therapy.

PMID- 19100721
TI  - Dynamic regional changes of extracellular ascorbic acid during global cerebral
      ischemia: studied with in vivo microdialysis coupled with on-line electrochemical
      detection.
AB  - The morphologic and functional outcomes of cerebral ischemia generally result
      from the acute neurochemical changes that occur 1 h after cerebral ischemia. As
      one of the small chemical species, ascorbic acid (AA) is involved in almost all
      kinds of neurochemical processes in acute cerebral ischemia. To understand the
      neurochemical processes in global cerebral ischemia, this study compares the
      dynamic regional changes of extracellular AA level, with in vivo microdialysis
      coupled with on-line electrochemical detection, in four different brain regions,
      1 h after global cerebral ischemia induced by two-vessel occlusion (2-VO). The
      regional distribution of physiological AA levels in the microdialysates from
      striatum, cortex, dorsal hippocampus, and ventral hippocampus were 2.97 +/- 0.06,
      3.98 +/- 0.09, 3.02 +/- 0.47, and 3.80 +/- 0.29 microM, respectively. In 1 h
      after 2-VO cerebral ischemia, the microdialysate AA levels in the above four
      regions varied in a different manner; the striatum AA slowly decreased to 86.49
      +/- 5.53% of the basal level (n=3, P<0.05). The AA levels in the cortex, dorsal
      hippocampus, and ventral hippocampus increased to 549.80 +/- 167.86 % (n=3,
      P<0.05), 167.81 +/- 41.85 % (n=4, P<0.05) and 261.24 +/- 65.00% (n=3, P<0.05), in
      relation to their respective basal levels, respectively. The recorded
      spatiotemporal regional changes in the extracellular AA levels essentially
      reflect the intricate neurochemical changes during the acute period of global
      cerebral ischemia and may thus be useful for understanding the neurochemical
      processes of global cerebral ischemia.

PMID- 19100722
TI  - CCL3L1 prevents gp120-induced neuron death via the CREB cell signaling pathway.
AB  - Neurodegeneration is a characteristic feature of AIDS dementia complex and is
      commonly associated with neuronal death in the brains of both pediatric and adult
      patients. Neuronal death associated with AIDS dementia complex can be induced by
      the HIV-1 protein gp120, but the underlying signal transduction mechanism remains
      unclear, especially for HIV-1 subtypes commonly seen in China. We have now
      demonstrated that the human CC ligand 3-like protein 1 (CCL3L1), a member of the
      CC chemokine family, appears to protect neuronal cultures through its ability to
      attenuate gp120-induced neuronal death. We found that (i) both pCREB levels and
      Bcl-2 expression are up-regulated in neuronal culture following treatment with
      CCL3L1 plus gp120; (ii) CCL3L1 induces cell survival via phosphorylation of CREB
      by way of the PKA and CaMKI/CaMKIV cell signaling pathways; (iii) transcription
      of the cell survival gene bcl-2 is induced by pCREB; and (iv) CCL3L1 protects
      cultured neurons against CCR5-mediated excitotoxicity induced by gp120. Thus, the
      CCL3L1/bcl-2-regulated anti-apoptotic pathway significantly contributes to
      reduction of HIV-1/gp120-induced neuronal apoptosis, and therefore, CCL3L1 should
      be further investigated as a potential chemokine to protect against neuronal
      injury in gp120-related neuronal toxicity.

PMID- 19100723
TI  - Alterations of prodynorphin gene expression in the rat mesocorticolimbic system
      during heroin self-administration.
AB  - Opiate-induced alterations in the gene expression of the opioid propeptides
      prodynorphin (PDYN) and proenkephalin (PENK) in the brain have previously been
      described. However, there are no studies examining opioid propeptide system
      alterations due to long-lasting heroin self-administration. In our study, using
      in situ hybridization, we measured PDYN and PENK mRNA levels in the dorsal
      striatum, central nucleus of amygdala (CEA), and nucleus accumbens (NAcc) shell
      and core in rats after 6 weeks of heroin self-administration (fixed ratio 5, 0.02
      mg/kg/infusion of heroin i.v.) and their respective saline or heroin "yoked"
      control. Our results show an increase in the PDYN mRNA level in the CEA and NAcc
      shell and no changes of PENK gene expression after heroin self-administration. In
      addition, to dissociate pharmacological effects of heroin from those produced by
      motivational processes driving active heroin intake on the PDYN and PENK gene
      expression, we compared effects of response-dependent (contingent) and response
      independent (noncontingent--"yoked" heroin control) heroin administration. We
      found no differences between contingent and noncontingent groups of rats. In
      conclusion, our results indicate neuroadaptations in the PDYN but not PENK gene
      expression in rat limbic forebrain during heroin self-administration. We show
      that such changes depend on direct pharmacological actions of heroin rather than
      contingent heroin intake. These neuroalterations probably occur as an adaptation
      to long-lasting heroin exposure and may underlie changes leading to compulsive
      drug use and addiction.

PMID- 19100724
TI  - Contribution of apamin-sensitive SK channels to the firing precision but not to
      the slow afterhyperpolarization and spike frequency adaptation in snail neurons.
AB  - Apamin-sensitive small conductance Ca(2+)-dependent K(+)(SK) channels are
      generally accepted as responsible for the medium afterhyperpolarization (mAHP)
      after single or train of action potentials. Here, we examined the functional
      involvement of these channels in the firing precision, post train AHP and spike
      frequency adaptation (SFA) in neurons of snail Caucasotachea atrolabiata. Apamin,
      a selective SK channel antagonist, reduced the duration of single-spike AHP and
      disrupted the spontaneous rhythmic activity. High frequency trains of evoked
      action potentials showed a time-dependent decrease in the action potential
      discharge rate (spike frequency adaptation) and followed by a prominent post
      stimulus inhibitory period (PSIP) as a marker of slow AHP (sAHP). Neither sAHP
      nor SFA was attenuated by apamin, suggesting that apamin-sensitive SK channels
      can strongly affect the rhythmicity, but are probably not involved in the SFA and
      sAHP. Nifedipine, antagonist of L-type Ca(2+) channels, decreased the firing
      frequency and neuronal rhythmicity. When PSIP was normalized to the background
      interspike interval, a suppressing effect of nifedipine on PSIP was also
      observed. Intracellular iontophoretic injection of BAPTA, a potent Ca(2+)
      chelator, dramatically suppressed PSIP that confirms the intracellular Ca(2+)
      dependence of the sAHP, but had no discernable effect on the SFA. During train
      evoked activity a reduction in the action potential overshoot and maximum
      depolarization rate was also observed, along with a decrease in the firing
      frequency, while the action potential threshold increased, which indicated that
      Na(+) channels, rather than Ca(2+)-dependent K(+) channels, are involved in the
      SFA.

PMID- 19100725
TI  - No evidence for a late locus of task switch effects.
AB  - When participants are asked to switch from one task to another, reaction time is
      longer than in task repetition trials. Current models assume that switch costs
      are located either at the perceptual stage or at the response selection stage.
      Contrary to this assumption, Hsieh and Liu ([2005. The nature of switch cost:
      task set configuration or carry-over effect? Cogn. Brain Res. 22,165-175]) found
      that task switching affects the response-locked lateralized readiness potential
      and thus provided evidence for a motor locus of switch costs. We hypothesized
      that this finding may have been due to methodological artefacts. In order to test
      this hypothesis, we replicated the experiment by Hsieh and Liu (2005) but avoided
      some potential methodological artefacts of their study. Our results showed a
      clear effect of task switching on the stimulus-locked lateralized readiness
      potential but no effect on the response-locked lateralized readiness potential.
      Thus, the present study questions the evidence for a late, motor locus of task
      switch effects but rather indicates a locus at the response selection stage.

PMID- 19100726
TI  - Changes in NGF and NT-3 protein species in the superior cervical ganglion
      following axotomy of postganglionic axons.
AB  - Mature sympathetic neurons in the superior cervical ganglion (SCG) are regulated
      by target-derived neurotrophins such as nerve growth factor (NGF) and
      neurotrophin-3 (NT-3). High molecular weight NGF species and mature NT-3 are the
      predominant NGF and NT-3 protein isoforms in the SCG, yet it is unknown whether
      the presence of these species is dependent on intact connection with the target
      tissues. In an attempt to determine the role of peripheral targets in regulating
      the neurotrophin species found in the SCG, we investigated the NGF and NT-3
      protein species present in the SCG following axotomy (transection) or injury of
      the post-ganglionic axons. Following a 7 day axotomy, the 22-24 kDa NGF species
      and the mature 14 kDa NT-3 species in the SCG were significantly reduced by 99%
      and 66% respectively, suggesting that intact connection with the target is
      necessary for the expression of these protein species. As expected, tyrosine
      hydroxylase (TH) protein in the SCG was significantly reduced by 80% at 7 days
      following axotomy. In order to distinguish between the effects of injury and loss
      of target connectivity, the SCG was examined following compression injury to the
      post-ganglionic nerves. Following injury, no reduction in the 22-24 kDa NGF or 14
      kDa mature NT-3 species was observed in the SCG. TH protein was slightly, yet
      significantly, decreased in the SCG following injury. The findings of this study
      suggest that the presence of the 22-24 kDa NGF and mature 14 kDa NT-3 species in
      the SCG is dependent on connection with peripheral targets and may influence, at
      least in part, TH protein expression in adult sympathetic neurons.

PMID- 19100728
TI  - Wnt5a is essential for intestinal elongation in mice.
AB  - Morphogenesis of the mammalian small intestine entails extensive elongation and
      folding of the primitive gut into a tightly coiled digestive tube. Surprisingly,
      little is known about the cellular and molecular mechanisms that mediate the
      morphological aspects of small intestine formation. Here, we demonstrate that
      Wnt5a, a member of the Wnt family of secreted proteins, is essential for the
      development and elongation of the small intestine from the midgut region. We
      found that the small intestine in mice lacking Wnt5a was dramatically shortened
      and duplicated, forming a bifurcated lumen instead of a single tube. In addition,
      cell proliferation was reduced and re-intercalation of post-mitotic cells into
      the elongating gut tube epithelium was disrupted. Thus, our study demonstrates
      that Wnt5a functions as a critical regulator of midgut formation and
      morphogenesis in mammals.

PMID- 19100727
TI  - Regulation of apoptosis of rbf mutant cells during Drosophila development.
AB  - Inactivation of the retinoblastoma gene Rb leads to defects in cell
      proliferation, differentiation, or apoptosis, depending on specific cell or
      tissue types. To gain insights into the genes that can modulate the consequences
      of Rb inactivation, we carried out a genetic screen in Drosophila to identify
      mutations that affected apoptosis induced by inactivation of the Retinoblastoma
      family protein (rbf) and identified a mutation that blocked apoptosis induced by
      rbf. We found this mutation to be a new allele of head involution defective (hid)
      and showed that hid expression is deregulated in rbf mutant cells in larval
      imaginal discs. We identified an enhancer that regulates hid expression in
      response to developmental cues as well as to radiation and demonstrated that this
      hid enhancer is directly repressed by RBF through an E2F binding site. These
      observations indicate that apoptosis of rbf mutant cells is mediated by an
      upregulation of hid. Finally, we showed that bantam, a miRNA that regulates hid
      translation, is expressed in the interommatidial cells in the larval eye discs
      and modulates the survival of rbf mutant cells.

PMID- 19100729
TI  - Translational repression of gurken mRNA in the Drosophila oocyte requires the
      hnRNP Squid in the nurse cells.
AB  - Establishment of the Drosophila dorsal-ventral axis depends upon the correct
      localization of gurken mRNA and protein within the oocyte. gurken mRNA becomes
      localized to the presumptive dorsal anterior region of the oocyte, but is
      synthesized in the adjoining nurse cells. Normal gurken localization requires the
      heterogeneous nuclear ribonucleoprotein Squid, which binds to the gurken 3'
      untranslated region. However, whether Squid functions in the nurse cells or the
      oocyte is unknown. To address this question, we generated genetic mosaics in
      which half of the nurse cells attached to a given oocyte are unable to produce
      Squid. In these mosaics, gurken mRNA is localized normally but ectopically
      translated during the dorsal anterior localization process, even though the
      oocyte contains abundant Squid produced by the wild type nurse cells. These data
      indicate that translational repression of gurken mRNA requires Squid function in
      the nurse cells. We propose that Squid interacts with gurken mRNA in the nurse
      cell nuclei and, together with other factors, maintains gurken in a
      translationally silent state during its transport to the dorsal anterior region
      of the oocyte. This translational repression is not required for gurken mRNA
      localization, indicating that the information repressing translation is separable
      from that regulating localization.

PMID- 19100730
TI  - The regulatory mechanisms that underlie inappropriate transcription of the
      myogenic determination gene Myf5 in the central nervous system.
AB  - Myf5 is a key myogenic determination factor, specifically present at sites of
      myogenesis. Surprisingly, during mouse development, this gene is also transcribed
      in restricted areas of the central nervous system, although the Myf5 protein is
      not detectable. We have investigated the regulation of Myf5 expression in the
      central nervous system. Using both in ovo electroporation in the chick embryo and
      transgenesis in the mouse, we show that regulatory sequences that direct neuronal
      Myf5 transcription are present in a distal element located between -55 and -54.3
      Kb from the Myf5 gene. An Oct6/Tst1 binding site is required for embryonic brain
      expression, and in the Oct6 mutant mouse embryo, Myf5 transcripts are no longer
      detectable in the brain. The Wnt-beta catenin signalling pathway is also
      implicated. Finally we show that post-transcriptional regulation of Myf5 gene
      expression involves miRNA repression acting through the Myf5-3'UTR.

PMID- 19100731
TI  - Tumor necrosis factor (TNF) receptor-2-mediated DNA synthesis and proliferation
      in primary cultures of adult rat hepatocytes: The involvement of endogenous
      transforming growth factor-alpha.
AB  - We investigated the effects of tumor necrosis factor (TNF)-alpha on DNA synthesis
      and proliferation, and its signal transduction pathways in primary cultures of
      adult rat hepatocytes. TNF-alpha induced time- and dose-dependent increases in
      hepatocyte DNA synthesis and proliferation. The hepatocyte proliferation
      stimulated by 30 ng/ml TNF-alpha was significantly inhibited by anti-TNF receptor
      2 antibody, but not by anti-TNF receptor 1 antibody. TNF-alpha-induced hepatocyte
      DNA synthesis and proliferation were blocked by AG1478 (10(-7) M), PD98059 (10(
      6) M), LY 294002 (10(-7) M), and rapamycin (100 ng/ml). TNF-alpha at 30 ng/ml
      significantly increased phosphorylation of receptor tyrosine kinase (175 kDa) and
      p42 mitogen-activated protein (MAP) kinase. This data suggests that the
      proliferative signal for primary cultured hepatocytes induced by TNF-alpha is
      mediated by TNF receptor 2 and the receptor tyrosine kinase/MAP kinase pathway.
      In addition, TNF-alpha-induced hepatocyte mitogenesis was significantly blocked
      by somatostatin (10(-6) M), adenylate cyclase inhibitor dideoxyadenosine (10(-7)
      M), protein kinase A inhibitor H-89 (10(-7) M), and neutralizing antibody to
      transforming growth factor (TGF)-alpha in culture. Indeed, 30 ng/ml TNF-alpha was
      found to rapidly stimulate secretion of TGF-alpha, and this secretion was also
      blocked by anti-TNF receptor 2 antibody. Moreover, TGF-alpha secretion induced by
      TNF-alpha was suppressed by dideoxyadenosine, H-89, and somatostatin. Together,
      these results indicate that stimulation of TNF receptor 2 by 30 ng/ml TNF-alpha
      induces autocrine secretion of TGF-alpha via the adenylate cyclase/protein kinase
      A pathway, after which TGF-alpha induces hepatocyte DNA synthesis and
      proliferation through the TGF-alpha receptor-linked tyrosine kinase (175 kDa)/MAP
      kinase signaling system.

PMID- 19100732
TI  - Oroxylin A suppresses invasion through down-regulating the expression of matrix
      metalloproteinase-2/9 in MDA-MB-435 human breast cancer cells.
AB  - Our previous study revealed that oroxylin A, a naturally occurring monoflavonoid
      isolated from Scutellariae radix, could inhibit the proliferation of human
      hepatocellular carcinoma HepG2 cells through inducing the apoptosis in these
      cells. However, the molecular mechanism of its anticancer activity remains poorly
      understood and warrants further investigations. In this study, we examined the
      anti-invasive activities of oroxylin A in vitro. The results showed that oroxylin
      A suppressed MDA-MB-435 cell adhesion to the fibronectin-coated substrate in a
      concentration-dependent manner. It inhibited the wound healing migration of MDA
      MB-435 cells and invasion of MDA-MB-435 cells through reconstituted extracellular
      matrix (matrigel). Zymography revealed that oroxylin A decreased the secretion of
      matrix metalloproteinases-2 (MMP-2) and metalloproteinases-9 (MMP-9). Oroxylin A
      also inhibited the expressions of MMP-2 and MMP-9 in MDA-MB-435 cells.
      Additionally, oroxylin A exerted an inhibitory effect on the phosphorylation of
      extracellular regulated proteinkinases1/2 (ERK1/2). Collectively, these data
      provided a molecular basis for the antiinvasive effects of oroxylin A. Taken
      together, these findings strongly suggest that oroxylin A had potential anti
      metastatic effect in vitro and shed light on the investigation of oroxylin A on
      breast cancer metastasis in vivo.

PMID- 19100733
TI  - Effects of hypertension on vasorelaxation to endocannabinoids in vitro.
AB  - The hypotensive actions of methanandamide are enhanced in anaesthetised
      spontaneously hypertensive rats (SHR), which may be due to increased sensory
      nerve activity. We have now investigated in vitro the role of sensory nerves and
      other vasorelaxant mechanisms of anandamide in this model of hypertension, and in
      rats made hypertensive by chronic inhibition of nitric oxide (NO) synthase. Male
      SHR and Sprague-Dawley rats (given approximately 10 mg/kg/day N(G) nitro-L
      arginine methyl ester (L-NAME) to drink for 4 weeks) were used. Vasorelaxant
      responses to anandamide and capsaicin were determined in perfused mesenteric
      arterial beds and thoracic aortic rings. The contributions of sensory nerves, NO,
      prostanoids, cannabinoid receptors and the endothelium in these responses were
      investigated. In mesenteric arterial beds from SHR, anandamide was less potent as
      a vasorelaxant, but in aortae caused greater maximal relaxations compared to
      controls. The reduced potency in the mesenteric arterial bed was accompanied by
      impaired NO-dependent relaxation. Pre-treatment with capsaicin prevented the
      enhancement of vasorelaxation by anandamide in mesenteric arterial beds from rats
      with L-NAME-induced hypertension. The reduced potency of anandamide in mesenteric
      arterial beds from SHR was due to reduced NO-dependent vasorelaxation, and
      provides no evidence for increased sensory nerve activity. The enhanced responses
      in the SHR aortae were endothelium-dependent. However, in L-NAME-induced
      hypertension the enhanced vasorelaxation to anandamide in the mesenteric
      vasculature was due to increased sensory nerve-mediated activity. In conclusion,
      the alterations in responses to anandamide in hypertension are dependent on the
      vessels studied and the model of hypertension.

PMID- 19100734
TI  - One step ahead: role of filopodia in adhesion formation during cell migration of
      keratinocytes.
AB  - Cell adhesion is an essential prerequisite for cell function and movement. It
      depends strongly on focal adhesion complexes connecting the extracellular matrix
      to the actin cytoskeleton. Especially in moving cells focal adhesions are highly
      dynamic and believed to be formed closely behind the leading edge. Filopodia were
      thought to act mainly as guiding cues using their tip complexes for elongation.
      Here we show for keratinocytes a strong dependence of lamellipodial adhesion
      sites on filopodia. Upon stable contact of the VASP-containing tip spot to the
      substrate, a filopodial focal complex (filopodial FX) is formed right behind
      along the filopodia axis. These filopodial FXs are fully assembled, yet small
      adhesions containing all adhesion markers tested. Filopodial FXs when reached by
      the lamellipodium are just increased in size resulting in classical focal
      adhesions. At the same time most filopodia regain their elongation ability.
      Blocking filopodia inhibits development of new focal adhesions in the
      lamellipodium, while focal adhesion maturation in terms of vinculin exchange
      dynamics remains active. Our data therefore argue for a strong spatial and
      temporal dependence of focal adhesions on filopodial focal complexes in
      keratinocytes with filopodia not permanently initiated via new clustering of
      actin filaments to induce elongation.

PMID- 19100735
TI  - The involvement of GABA-C receptors in paired-pulse depression of inhibitory
      postsynaptic currents in rat hippocampal CA1 pyramidal neurons.
AB  - In rat hippocampal CA1 pyramidal neurons, gamma-aminobutyric acid (GABA) A
      receptor-mediated inhibitory postsynaptic currents (IPSCs) undergo a paired-pulse
      depression (PPD) by the second of two pulses, with inter-pulse intervals of 100
      2000 ms, applied to the stratum radiatum. While GABA-C receptors are described in
      the CA1 area, their functional significance is unknown. In this study, the
      involvement of GABA-C receptors in PPD was examined using an in vitro hippocampal
      slice preparation. IPSCs evoked by stimulations in stratum radiatum were recorded
      with patch pipettes from CA1 pyramidal cells. PPD, when induced in the above
      fashion, was blocked by the GABA-C receptor antagonist (1,2,5,6-Tetrahydropyridin
      4-yl) methylphosphinic acid (TPMPA, 10 muM, applied in the superfusing medium).
      GABA-A and GABA-B receptor-mediated IPSCs, as well as the baclofen-induced
      suppression of the GABA-A receptor mediated IPSC, were not antagonized by TPMPA
      (10-20 muM). These results indicate that PPD of the IPSC is mediated by the
      activation of GABA-C receptors.

PMID- 19100736
TI  - High dose of simvastatin induces hyperlocomotive and anxiolytic-like activities:
      The association with the up-regulation of NMDA receptor binding in the rat brain.
AB  - Statins are widely being used for the treatment of a variety of conditions beyond
      their original indication for lowering cholesterol. We have previously reported
      that simvastatin affected the dopaminergic system in the rat brain. This study
      aims to investigate locomotor and anxiety effects along with the regional changes
      of N-methyl-d-aspartate (NMDA) receptors in the rat brain after 4-week
      administration of simvastatin. Hyperlocomotive and anxiolytic-like activities in
      the rat were observed after chronic administration of high dose simvastatin (10
      mg/kg/day). Distributions and alterations of NMDA receptors in the post-mortem
      rat brain were detected by [(3)H] MK-801 binding autoradiography. Simvastatin
      increased [(3)H] MK-801 binding, predominantly in the prefrontal cortex (20%,
      p=0.003), primary motor cortex (20%, p<0.001), cingulate cortex (28%, p<0.001),
      hippocampus (41%, p<0.001), caudate putamen (30%, p=0.029), nucleus accumbens
      (27%, p=0.035) and amygdala (45%, p<0.001) compared to controls. Significant
      positive correlations were identified between hyperlocomotive as well as
      anxiolytic-like activities and the upregulation of NMDA receptors in different
      brain regions. Our results also provide strong evidence that chronic high dose
      simvastatin administration is to exhibit NMDA antagonist-like effects, which
      would partially explain the anxiolytic and hyperlocomotor activities. These
      findings contribute to a better understanding of the critical roles of
      simvastatin in modulating psycho-neurodegenerative disorders, via NMDA receptors.

PMID- 19100737
TI  - Distribution of Foxp3(+) T-regulatory cells in experimental autoimmune neuritis
      rats.
AB  - T-regulatory cells expressing the forkhead box transcription factor 3 (Foxp3)
      play essential roles in immune homeostasis. Experimental autoimmune neuritis
      (EAN) is an autoantigen-specific T-cell-mediated disease model for human
      demyelinating inflammatory disease of the peripheral nervous system. We
      investigated the distribution of Foxp3(+) cells in sciatic nerves, spleen and
      lymph nodes of EAN rats, and the influence of FTY720 on the localization of
      Foxp3(+) cells in EAN rats. In sciatic nerves of EAN rats, accumulation of
      Foxp3(+) cells was not seen during the pre-symptomatic phase (until Day 9) or
      during early or peak disease activity. In contrast, Foxp3(+) cell accumulation
      was regularly seen in the recovery from neurologic disease, suggesting a
      contribution of Foxp3(+) cells to the resolution of EAN. FTY720 was given at
      onset of EAN (Day 10) until Day 18. Following FTY720 administration, percentages
      of Foxp3(+) cells in EAN rats were increased in circulating blood, but reduced in
      lymph nodes compared to the PBS control. FTY720 treatment suppressed total
      numbers but increased percentages of Foxp3(+) cells in sciatic nerves of EAN
      rats. These data not only suggests a protective role of Foxp3(+) cells in EAN but
      also provides a potential way to alter localization of Foxp3(+) cells in vivo.

PMID- 19100738
TI  - Glucose-induced production of hydrogen sulfide may protect the pancreatic beta
      cells from apoptotic cell death by high glucose.
AB  - We examined the expression of the major H(2)S-producing enzymes, cystathionine
      beta-synthase (CBS) and cystathionine-gamma-lyase (CSE). CBS was ubiquitously
      distributed in the mouse pancreas, but CSE was found only in the exocrine.
      Freshly isolated islets expressed CBS, while CSE was faint. However, high glucose
      increased the CSE expression in the beta-cells. L-Cysteine or NaHS suppressed
      islet cell apoptosis with high glucose, and increased glutathione content in MIN6
      beta-cells. Pretreatment with L-cysteine improved the secretory responsiveness
      following stimulation with glucose. The CSE inhibitor DL-propargylglycine
      antagonized these L-cysteine effects. We suggest H(2)S may function as an
      'intrinsic brake' which protects beta-cells from glucotoxicity.

PMID- 19100739
TI  - Modeling the evolution of the MC2R and MC5R genes: studies on the cartilaginous
      fish, Heterondotus francisci.
AB  - Comparative studies support the hypothesis that the proliferation of melanocortin
      receptor genes (MCRs) in gnathostomes corresponds to the 2R hypothesis for the
      radiation of gene families in Phylum Chordata. This mini-review will initially
      focus on the distribution of MCRs in cartilaginous fish and the relationship
      between the shark MC5R gene and the proposed ancestral MC5R/2R gene. This section
      will be followed by the results of recent studies on the features of the ligand
      binding site common to all melanocortin receptors. These data will provide the
      background for a set of hypotheses to explain the unique ligand selectivity of
      the MC2 receptor in teleosts and tetrapods.

PMID- 19100740
TI  - Social modulation of androgens in male birds.
AB  - Most seasonally reproducing vertebrates show pronounced changes in testosterone
      levels throughout the year. The Challenge Hypothesis [Wingfield, J.C., Hegner,
      R.E., Dufty, A.M., Ball, G. F., 1990. The "challenge hypothesis": theoretical
      implications for patterns of testosterone secretion, mating systems, and breeding
      strategies. Am. Nat. 136, 829-846] predicts that seasonal patterns in circulating
      androgen concentrations vary as a function of mating system, male-male aggression
      and paternal care. In most comparative studies, the predictions of the Challenge
      Hypothesis have been tested primarily by calculating the ratio between breeding
      peak and breeding baseline testosterone concentrations, using this ratio as a
      proxy for the effect that social interactions have on testosterone levels
      (androgen responsiveness R). Recently, we suggested that it is preferable to
      separate the seasonal testosterone response (R(season)) from the androgen
      responsiveness to male-male interactions (R(male-male)), as these two measures do
      not correlate and can differ both in magnitude and direction [Goymann, W.,
      Landys, M.M., Wingfield, J.C., 2007. Distinguishing seasonal androgen responses
      from male-male androgen responsiveness-revisiting the Challenge Hypothesis. Horm.
      Behav. 51, 463-476]. Here, I discuss several methodological and ecological
      factors that may explain why R(season) and R(male-male) differ. Furthermore, I
      describe three other kinds of androgen responsiveness, namely the androgen
      responsiveness of males to receptive females (R(male-female)), to non-social
      environmental cues (R(environment)), and the potential androgen responsiveness
      (R(potential)). The latter is measured before and after an injection of
      gonadotropin releasing hormone (GnRH), which typically leads to a maximal release
      of testosterone from the testes. I argue that separation of different kinds of
      androgen responsiveness and putting them into context with the natural history
      and ecology of a study species may help to better understand variations in
      androgen responsiveness to social and non-social environmental factors. On an
      ultimate level this may help to better understand the benefits and costs of
      increasing, or not increasing testosterone concentrations during social
      interactions. Proximately, this will aid in a more complete understanding of the
      mechanisms by which testosterone regulates behavioral traits and by which
      behavior feeds back on hormone levels.

PMID- 19100741
TI  - A method for identification of HIV gp140 binding memory B cells in human blood.
AB  - Antibodies to HIV are potentially important reagents for basic and clinical
      studies. Historically, these reagents have been produced by random cloning of
      heavy and light chains in phage display libraries [Burton, D.R., Barbas, C.F.
      III, Persson, M.A.A., Koenig, S., Chanock, R.M., and Lerner, R.A., (1991), A
      large array of human monoclonal antibodies to type 1 immunodeficiency virus from
      combinatorial libraries of asymptomatic seropositive individuals. Proc. Natl.
      Acad. Sci. U. S. A. 88, 10134-10137.] and electrofusion techniques [Buchacher,
      A., Predl, R., Tauer, C., Purtscher, M., Gruber, G., Heider, R., Steindl, F.,
      Trkola, A., Jungbauer, A., and Katinger, H., (1992), Human monoclonal antibodies
      against gp41 and gp120 as potential agent for passive immunization. Vaccines 92,
      191-195]. Here we describe a method to identify and potentially enrich human
      memory B cells from HIV infected patients that show serum titers of neutralizing
      antibodies. When biotinylated gp140 is used to stain peripheral blood mononuclear
      cells it identifies a distinct population of gp140 binding B cells by flow
      cytometry.

PMID- 19100742
TI  - From behavior to fictive feeding: anatomy, innervation and activation pattern of
      pharyngeal muscles of Calliphora vicina 3rd instar larvae.
AB  - A description of the muscles and nerves involved in feeding of larval Calliphora
      vicina is given as a prerequisite to establish fictive feeding patterns recorded
      from the isolated central nervous system. Feeding Diptera larvae show a
      repetitive sequence of pro- and retraction of the cephalopharyngeal skeleton
      (CPS), elevation and depression of the mouth hooks and food ingestion. The
      corresponding pharyngeal muscles are protractors, mouth hook elevators and
      depressors, the labial retractor and cibarial dilator muscles. These muscles are
      innervated by the prothoracic accessory nerve (PaN), maxillary nerve (MN) and
      antennal nerve (AN) as shown electrophysiologically by recording action
      potentials from the respective nerve that correlate to post-synaptic potentials
      on the muscles. All three nerves show considerably more complex branching
      patterns than indicated in the literature. Extracellular recordings from the
      stumps of PaN, MN and AN connected to an isolated CNS show spontaneous rhythmic
      motor patterns that reflect the feeding sequence in intact larvae. Variability of
      the feeding pattern observed in behavioral experiments is also evident from the
      level of motor output from an isolated CNS. The data obtained from Calliphora
      will facilitate electrophysiological investigations dealing with the genetic
      background of feeding behavior in Drosophila larvae.

PMID- 19100743
TI  - Rectal sac distention is induced by 20-hydroxyecdysone in the pupa of Bombyx
      mori.
AB  - Holometabolous insects do not excrete but store metabolic wastes during the pupal
      period. The waste is called meconium and is purged after adult emergence.
      Although the contents of meconium are well-studied, the developmental and
      physiological regulation of meconium accumulation is poorly understood. In Bombyx
      mori, meconium is accumulated in the rectal sac; thereby, the rectal sac distends
      at the late pupal stage. Here, we show that rectal sac distention occurs between
      4 and 5 days after pupation. The distention is halted by brain-removal just after
      larval-pupal ecdysis but not by brain-removal 1 day after pupation. In the pupae,
      brain-removal just after ecdysis kept the hemolymph ecdysteroid titer low during
      early and mid-pupal stages. An injection of 20-hydroxyecdysone (20E) evoked the
      distention that was halted by brain-removal in a dose-dependent manner.
      Therefore, brain-removal caused the lack of ecdysteroid, and rectal sac
      distention did not appear in the brain-removed pupae because of the lack of
      ecdysteroid. We conclude that rectal sac distention is one of the developmental
      events regulated by 20E during the pupal period in B. mori.

PMID- 19100744
TI  - Morph-associated JH titer diel rhythm in Gryllus firmus: Experimental
      verification of its circadian basis and cycle characterization in artificially
      selected lines raised in the field.
AB  - Previous studies demonstrated a high-amplitude, diel cycle for the hemolymph JH
      titer in the wing-polymorphic cricket, Gryllus firmus. The JH titer rose and fell
      in the flight-capable morph (long-winged, LW(f)) above and below the relatively
      temporally invariant JH titer in the flightless (short-winged, SW) morph. The
      morph-specific JH titer cycle appeared to be primarily driven by a morph-specific
      diel cycle in the rate of JH biosynthesis. In the present study, cycles of the JH
      titer and rate of JH biosynthesis in the LW(f) morph persisted in the laboratory
      under constant darkness with an approximate 24h periodicity. The JH titer cycle
      also shifted in concert with a shift in the onset of the scotophase, was
      temperature compensated in constant darkness, and became arrhythmic under
      constant light. These results provide strong support for the circadian basis of
      the morph-specific diel rhythm of the JH titer and JH biosynthetic rate.
      Persistence of the JH titer cycle under constant darkness in multiple LW-selected
      and SW-selected stocks also provides support for the genetic basis of the morph
      associated circadian rhythm. The morph-specific JH titer cycle was observed in
      these stocks raised in the field, in both males and females, in each of 3 years
      studied. The onset of the cycle in the LW(f) morph, a few hours before sunset,
      correlated well with the onset of the cycle, a few hours before lights-off, in
      the laboratory. The morph-specific JH titer cycle is a general feature of G.
      firmus, under a variety of environmental conditions, and is not an artifact of
      specific laboratory conditions or specific genetic stocks. It is a powerful
      experimental model to investigate the mechanisms underlying endocrine circadian
      rhythms, their evolution, and their impact on life history evolution.

PMID- 19100745
TI  - Novel mode of cooperative binding between myosin and Mg2+ -actin filaments in the
      presence of low concentrations of ATP.
AB  - Cooperative interaction between myosin and actin filaments has been detected by a
      number of different methods, and has been suggested to have some role in force
      generation by the actomyosin motor. In this study, we observed the binding of
      myosin to actin filaments directly using fluorescence microscopy to analyze the
      mechanism of the cooperative interaction in more detail. For this purpose, we
      prepared fluorescently labeled heavy meromyosin (HMM) of rabbit skeletal muscle
      myosin and Dictyostelium myosin II. Both types of HMMs formed fluorescent
      clusters along actin filaments when added at substoichiometric amounts.
      Quantitative analysis of the fluorescence intensity of the HMM clusters revealed
      that there are two distinct types of cooperative binding. The stronger form was
      observed along Ca(2+)-actin filaments with substoichiometric amounts of bound
      phalloidin, in which the density of HMM molecules in the clusters was comparable
      to full decoration. The novel, weaker form was observed along Mg(2+)-actin
      filaments with and without stoichiometric amounts of phalloidin. HMM density in
      the clusters of the weaker form was several-fold lower than full decoration. The
      weak cooperative binding required sub-micromolar ATP, and did not occur in the
      absence of nucleotides or in the presence of ADP and ADP-Vi. The G680V mutant of
      Dictyostelium HMM, which over-occupies the ADP-Pi bound state in the presence of
      actin filaments and ATP, also formed clusters along Mg(2+)-actin filaments,
      suggesting that the weak cooperative binding of HMM to actin filaments occurs or
      initiates at an intermediate state of the actomyosin-ADP-Pi complex other than
      that attained by adding ADP-Vi.

PMID- 19100747
TI  - Recognition of non-alpha-amino substrates by pyrrolysyl-tRNA synthetase.
AB  - Pyrrolysyl-tRNA synthetase (PylRS), an aminoacyl-tRNA synthetase (aaRS) recently
      found in some methanogenic archaea and bacteria, recognizes an unusually large
      lysine derivative, L-pyrrolysine, as the substrate, and attaches it to the
      cognate tRNA (tRNA(Pyl)). The PylRS-tRNA(Pyl) pair interacts with none of the
      endogenous aaRS-tRNA pairs in Escherichia coli, and thus can be used as a novel
      aaRS-tRNA pair for genetic code expansion. The crystal structures of the
      Methanosarcina mazei PylRS revealed that it has a unique, large pocket for amino
      acid binding, and the wild type M. mazei PylRS recognizes the natural lysine
      derivative as well as many lysine analogs, including N(epsilon)-(tert
      butoxycarbonyl)-L-lysine (Boc-lysine), with diverse side chain sizes and
      structures. Moreover, the PylRS only loosely recognizes the alpha-amino group of
      the substrate, whereas most aaRSs, including the structurally and genetically
      related phenylalanyl-tRNA synthetase (PheRS), strictly recognize the main chain
      groups of the substrate. We report here that wild type PylRS can recognize
      substrates with a variety of main-chain alpha-groups: alpha-hydroxyacid, non
      alpha-amino-carboxylic acid, N(alpha)-methyl-amino acid, and D-amino acid, each
      with the same side chain as that of Boc-lysine. In contrast, PheRS recognizes
      none of these amino acid analogs. By expressing the wild type PylRS and its
      cognate tRNA(Pyl) in E. coli in the presence of the alpha-hydroxyacid analog of
      Boc-lysine (Boc-LysOH), the amber codon (UAG) was recoded successfully as Boc
      LysOH, and thus an ester bond was site-specifically incorporated into a protein
      molecule. This PylRS-tRNA(Pyl) pair is expected to expand the backbone diversity
      of protein molecules produced by both in vivo and in vitro ribosomal translation.

PMID- 19100746
TI  - Epitope mapping of a bactericidal monoclonal antibody against the factor H
      binding protein of Neisseria meningitidis.
AB  - The factor H binding protein (fHbp) is a 27-kDa membrane-anchored lipoprotein of
      Neisseria meningitidis that allows the survival of the bacterium in human plasma;
      it is also a major component of a universal vaccine against meningococcus B. In
      this study, we used nuclear magnetic resonance spectroscopy, mutagenesis, and in
      silico modeling to map the epitope recognized by MAb502, a bactericidal
      monoclonal antibody elicited by fHbp. The data show that the antibody recognizes
      a conformational epitope within a well-defined area of the immunodominant C
      terminal domain of the protein that is formed by two loops connecting different
      beta-strands of a beta-barrel and a short alpha-helix brought in spatial
      proximity by the protein folding. The identification of the protective epitopes
      of fHbp is an important factor for understanding the mechanism(s) of an effective
      immune response and provides valuable guidelines for designing variants of the
      protein able to induce broadly protective immunity.

PMID- 19100748
TI  - Sequence and structural features of enzymes and their active sites by EC class.
AB  - We have analysed a non-redundant set of 294 enzymes for differences in sequence
      and structural features between the six main Enzyme Commission (EC)
      classification groups. This systematic study of enzymes, and their active sites
      in particular, aims to increase understanding of how the structure of an enzyme
      relates to its functional role. Many features showed significant differences
      between the EC classes, including active-site polarity, enzyme size and active
      site amino acid propensities. Many attributes correlate with each other to form
      clusters of related features from which we chose representative features for
      further analysis. Oxidoreductases have more non-polar active sites, which can be
      attributed to cofactor binding and a preference for Glu over Asp in active sites
      in comparison to the other classes. Lyases form a significantly higher proportion
      of oligomers than any other class, whilst the hydrolases form the largest
      proportion of monomers. These features were then used in a prediction model that
      classified each enzyme into its top EC class with an accuracy of 33.1%, which is
      an increase of 16.4% over random classification. Understanding the link between
      structure and function is critical to improving enzyme design and the prediction
      of protein function from structure without transfer of annotation from
      alignments.

PMID- 19100749
TI  - Central nervous system fatigue alters autonomic nerve activity.
AB  - AIMS: Fatigue is a common symptom in modern society. In order to clarify the
      mechanisms underlying fatigue, we examined the association between central
      nervous system fatigue and autonomic nerve activity. MAIN METHODS: The study
      group consisted of 20 healthy subjects. They performed the 2-back test for 30 min
      to induce fatigue. Just before and after the fatigue-inducing session, they
      completed the advanced trail making test (ATMT) for 30 min as a fatigue
      evaluating task session. In order to measure autonomic nerve activity,
      electrocardiograms were monitored continuously throughout the experiment. KEY
      FINDINGS: After the fatigue-inducing task session, impaired task performance was
      demonstrated based on the total trial number and error counts of the ATMT. During
      the task session, although task performance as measured using the accuracy and
      the mean reaction time of the 2-back test was almost unchanged,
      electrocardiographic R-R wave interval analyses showed a decreased high-frequency
      component power and an increasing trend in the low-frequency component power/high
      frequency component power ratio. SIGNIFICANCE: Decreased vagal nerve activity and
      increased sympathetic nerve activity are associated with central nervous system
      fatigue.

PMID- 19100750
TI  - Norcantharidin reduced cyclins and cytokines production in human peripheral blood
      mononuclear cells.
AB  - AIMS: To evaluate potential agents of therapeutic value in tissue inflammation,
      we studied norcantharidin (NCTD) and its derivatives for their effects on immune
      responses of human peripheral blood mononuclear cells (PBMC) in vitro. MAIN
      METHODS: PBMC proliferation was evaluated by tritiated thymidine uptake method.
      The production and gene expression of cytokines were determined with enzyme
      immunoassays (EIA) and reverse transcription-polymerase chain reaction (RT-PCR),
      respectively. KEY FINDINGS: Five derivatives from NCTD had no significant effect
      on cell proliferation in PBMC. NCTD inhibited PBMC proliferation induced by
      phytohemagglutinin (PHA) with a 50% inhibitory concentration (IC(50)) 42.1+/-2.3
      microM. The inhibitory action of NCTD did not involve direct cytotoxicity. To
      localize the point in the PBMC proliferation where arrest occurred, a set of key
      regulatory events leading to the cell proliferation, including cell cycle
      progression, production and gene expression of interleukin-2 (IL-2), IL-4, IL-10,
      and interferon-gamma (IFN-gamma) and cyclins was examined. Data demonstrated NCTD
      arrested the cell cycle progression of activated PBMC from the G1 transition to
      the S phase. The cyclin D3, E, A, and B transcripts and protein production in PHA
      treated PBMC was reduced by NCTD. Whereas NCTD exerted no effect on IL-4 and IFN
      gamma production, it significantly alleviated the production and mRNA expression
      of IL-2 and IL-10 in activated PBMC. SIGNIFICANCE: The suppressant effects of
      NCTD on proliferation of PBMC activated by PHA therefore appear to be mediated,
      at least in part, through inhibition of cyclins and IL-2 production and arrest of
      cell cycle progression in the cells.

PMID- 19100751
TI  - Dilinoleoylphosphatidylcholine ameliorates scopolamine-induced impairment of
      spatial learning and memory by targeting alpha7 nicotinic ACh receptors.
AB  - AIMS: The present study was conducted to understand the role of 1,2-dilynoleoyl
      sn-glycero-3-phosphocholine (DLPhtCho) in cognitive functions. MAIN METHODS: Two
      electrode voltage-clamp was made to Xenopus oocytes expressing rat alpha7
      acetylcholine (ACh) receptors. Field excitatory postsynaptic potentials (fEPSPs)
      were monitored from the CA1 region of rat hippocampal slices. Water maze test was
      carried out to assess spatial learning and memory for rats. KEY FINDINGS: In the
      oocyte expression system, DLPhtCho at a concentration of 10 microM potentiated
      ACh-evoked currents to approximately 190% of basal amplitudes 70 min after 10-min
      treatment. In contrast, 1-stearoyl-2-lynoleoyl-sn-glycero-3-phosphocholine
      (SLPhtCho), 1-palmitoyl-2-linoleoyl-sn-glycero-3-phosphocholine (PLPhtCho), and 1
      palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (POPhtCho) had no effect on the
      currents. DLPhtCho (10 microM) enhanced slope of fEPSPs to about 150% of basal
      levels at 70-min treatment, that is inhibited by alpha-bungarotoxin, an inhibitor
      of alpha7 ACh receptors, while no enhancement was obtained with SLPhtCho,
      PLPhtCho, or POPhtCho. In the water maze test, oral administration with DLPhtCho
      (5 mg/kg) significantly shortened the prolonged acquisition latency for rats
      intraperitoneally injected with scopolamine (1 mg/kg). SIGNIFICANCE: The results
      of the present study show that DLPhtCho improves scopolamine-induced learning and
      memory deficits, possibly by facilitating hippocampal synaptic transmission under
      the control of alpha7 ACh receptors. DLPhtCho, therefore, could be developed as a
      beneficial anti-dementia drug.

PMID- 19100752
TI  - Exercise status affects skin perfusion via prostaglandin, nitric oxide, and EDHF
      pathways in diabetes.
AB  - Participation in regular exercise training improves dorsal skin perfusion, while
      type 2 diabetes mellitus (T2 DM) often limits it via reductions in the action or
      release of vasodilatory compounds. This study was undertaken to investigate the
      relative contributions of prostaglandins (PG), nitric oxide (NO), and endothelial
      derived hyperpolarizing factor (EDHF) in dorsal foot skin perfusion in
      individuals with and without T2 DM and a sedentary lifestyle. Participants
      included 24 individuals with T2 DM and 28 nondiabetic controls whose exercise
      status was determined via questionnaire. Their dorsal foot skin perfusion was
      measured at rest using laser Doppler assessment during localized heating to 44
      degrees C with oral aspirin (ASA, 325 mg) treatment. In addition, they received
      an infusion via a subcutaneous microdialysis probe of either saline (left foot)
      or L-NAME, a NOS-inhibitor (right foot). Compared to normative data without ASA,
      heat-stimulated perfusion in regular exercisers (n=22) was significantly more
      suppressed by ASA and by ASA/L-NAME than in sedentary individuals (n=30). Chronic
      exercisers exhibit a greater reliance on PG and lesser involvement of EDHF with
      unchanged NO compared to sedentary individuals, who rely more on EDHF and less on
      PG release. One possible exception may be diabetic, sedentary individuals, who
      may rely somewhat more on NO than EDHF. These results suggest that regular
      exercise may exhibit the greatest effect on the normal functioning of these
      vasodilatory pathways, although diabetes and a sedentary state together may
      somewhat alter their relative importance.

PMID- 19100753
TI  - A robust estimator of mutation rates.
AB  - Fluctuation analysis is an established and widely used technique of estimating
      mutation rates in cultured cells. This paper presents a modified median estimator
      of mutation rates, which is novel because it allows for unequal population sizes
      N(t) of the parallel cultures, and helps to detect and reduce the estimation
      variability. Simulation results show a good accuracy and robustness of the
      modified median estimator compared with the median estimator and the maximum
      likelihood estimator. The proposed estimator, based on the Luria-Delbruck model,
      is applied to 20 yeast datasets collected during 3 different days for a study of
      chromosome loss and recombination in wild-type Saccharomyces cerevisiae strains.
      The estimates obtained display among-experiment variability, which is inflated
      with respect to the model predictions on simulated data. Further investigation in
      S. cerevisiae and Escherichia coli uncovers an empirical inverse relationship
      between the population sizes N(t) and the mutation rate estimates under certain
      experimental conditions. The impact of these effects on the practice of
      fluctuation analysis is discussed.

PMID- 19100754
TI  - Neglect dyslexia: frequency, association with other hemispatial neglects, and
      lesion localization.
AB  - Patients with right hemisphere injury often omit or misread words on the left
      side of a page or the beginning letters of single words (neglect dyslexia). Our
      study involving a large sample of acute right hemisphere stroke investigated (1)
      the frequency of neglect dyslexia (ND), (2) the association between ND and other
      types of contralesional hemispatial neglect (CN), (3) the effect of visual field
      defect (VFD) on ND, and (4) the anatomical substrates for ND. Participants were
      138 consecutive patients with right hemisphere stroke who underwent a neglect
      test battery including a test for ND. ND was considered present if the patient
      misread or omitted the left portion of the word in three or more of the 25 target
      words. CN was noted in 80/138 (58.0%) patients while ND was found in 31/138
      (22.5%) patients. Of the 80 patients with CN, the frequency of neglect based on
      ND test was only 37.5% while the frequency of neglect based on other neglect
      tasks ranged from 51.3% to 86.3%. The severity of neglect was a significant
      predictor for ND. VFD was also a significant predictor for the occurrence of ND
      but this effect disappeared when the severity of neglect was controlled. Patients
      with CN had lesions in the superior and middle temporal gyri, inferior parietal
      lobule, and posterior insular cortex; patients with ND had additional lesions in
      the lingual and fusiform gyri. In summary, ND was dissociated from other types of
      neglect and was most often associated with severe neglect. VFD contributed to the
      occurrence of ND. ND resulted from lesions of temporoparietal junction areas
      (inferior parietal/superior temporal gyri) combined with those of
      lingual/fusiform gyri.

PMID- 19100755
TI  - Prism adaptation improves visual search in hemispatial neglect.
AB  - Visuomotor prism adaptation has been found to induce a lateral bias of spatial
      attention in chronic hemispatial neglect patients. Here, two experiments were
      conducted to explore the effects of 10 degrees prism adaptation on visual search
      tasks and standard visual inattention tests. Baselines and intervention effects
      were measured on separate days for all patients. The first experiment explored
      whether prism adaptation affects performance on a time restricted visual search
      task (maximum 3500ms presentation followed by visual and auditory feedback). No
      positive effects of prism adaptation were found on accuracy in visual search nor
      on traditional neglect tests. These results accord well with previous studies
      showing that increased cognitive load can lead to prism de-adaptation or
      unchanged performance following prism adaptation. Response times in visual search
      became faster following intervention but this was not the case for the standard
      neglect tests. In the second experiment, the same single-featured search task was
      used, but the participants had unlimited search time and received no feedback on
      their response. This time, the patients showed accuracy improvements in visual
      search and all four on regular neglect tests. Therapeutic effects lasted for at
      least 90-120min. Response times on all tasks became faster after prism
      adaptation. The results are consistent with studies showing effects of prism
      adaptation on neuropsychological neglect tests and other attentional tasks that
      are not speeded or time restricted, where feedback is not provided, or are
      performed following non-feedback-based tasks. The current findings show that
      prism adaptation improves visual search in neglect and that these beneficial
      effects can disappear with feedback.

PMID- 19100757
TI  - Amnesia as an impairment of detail generation and binding: evidence from
      personal, fictional, and semantic narratives in K.C.
AB  - Autobiographical episodic recall involves active simultaneous generation and
      binding of various elements that were present during the initial experience.
      Deficits in this reconstructive process may account for some aspects of
      retrograde amnesia (RA) for personally experienced events. Constructive and
      reconstructive processes may involve similar mechanisms. If so, patients with
      extensive anterograde amnesia (AA) and RA should show deficits in non
      recollective cognitive domains, such as imagining events that had never been
      experienced and recounting non-personal narratives, that presumably rely on
      constructive and re-constructive processes, respectively. To test these
      possibilities, patient K.C., who has severe AA and RA for personal episodes, was
      asked to generate fictional events and to recall and recognize details of well
      known fairy tales and bible stories. K.C.'s performance on both tasks was better
      than expected given his severely impaired autobiographical episodic memory (AM),
      but significantly worse than that of control participants. K.C. was able to
      create a skeletal outline for both types of narratives, providing sufficient
      information to convey their gist, but the narratives were fragmented and lacking
      in detail. This deficit cannot be explained as resulting entirely from deficient
      stored semantic knowledge, because K.C. was able to discriminate between true and
      false details of non-personal semantic narratives on a recognition test, which he
      cannot do for personal events [Gilboa, A., Winocur, G., Rosenbaum, R.S., Poreh,
      A., Gao, F., Black, S.E., Westmacott, R., & Moscovitch, M. (2006a). Hippocampal
      contributions to recollection in retrograde and anterograde amnesia. Hippocampus,
      16, 966-980]. Thus, retrograde AM impairment may be viewed as both a loss of
      information as well as a deficit in reconstructive processes that hamper or
      prevent the binding of information to generate a cohesive, detail-rich memory.

PMID- 19100756
TI  - Aging reduces veridical remembering but increases false remembering:
      neuropsychological test correlates of remember-know judgments.
AB  - In 1985 Tulving introduced the remember-know procedure, whereby subjects are
      asked to distinguish between memories that involve retrieval of contextual
      details (remembering) and memories that do not (knowing). Several studies have
      been reported showing age-related declines in remember hits, which has typically
      been interpreted as supporting dual-process theories of cognitive aging that
      align remembering with a recollection process and knowing with a familiarity
      process. Less attention has been paid to remember false alarms, or their relation
      to age. We reviewed the literature examining aging and remember/know judgments
      and show that age-related increases in remember false alarms, i.e., false
      remembering, are as reliable as age-related decreases in remember hits, i.e.,
      veridical remembering. Moreover, a meta-analysis showed that the age effect size
      for remember hits and false alarms are similar, and larger than age effects on
      know hits and false alarms. We also show that the neuropsychological correlates
      of remember hits and false alarms differ. Neuropsychological tests of medial
      temporal lobe functioning were related to remember hits, but tests of frontal
      lobe functioning and age were not. By contrast, age and frontal-lobe functioning
      predicted unique variance in remember false alarms, but MTL functioning did not.
      We discuss various explanations for these findings and conclude that any
      comprehensive explanation of recollective experience will need to account for the
      processes underlying both remember hits and false alarms.

PMID- 19100758
TI  - Toward an integrated account of object and action selection: a computational
      analysis and empirical findings from reaching-to-grasp and tool-use.
AB  - The act of reaching for and acting upon an object involves two forms of
      selection: selection of the object as a target, and selection of the action to be
      performed. While these two forms of selection are logically dissociable, and are
      evidently subserved by separable neural pathways, they must also be closely
      coordinated. We examine the nature of this coordination by developing and
      analyzing a computational model of object and action selection first proposed by
      Ward [Ward, R. (1999). Interactions between perception and action systems: a
      model for selective action. In G. W. Humphreys, J. Duncan, & A. Treisman (Eds.),
      Attention, Space and Action: Studies in Cognitive Neuroscience. Oxford: Oxford
      University Press]. An interesting tenet of this account, which we explore in
      detail, is that the interplay between object and action selection depends
      critically on top-down inputs representing the current task set or plan of
      action. A concrete manifestation of this, established through a series of
      simulations, is that the impact of distractor objects on reaching times can vary
      depending on the nature of the current action plan. In order to test the model's
      predictions in this regard, we conducted two experiments, one involving direct
      object manipulation, the other involving tool-use. In both experiments we
      observed the specific interaction between task set and distractor type predicted
      by the model. Our findings provide support for the computational model, and more
      broadly for an interactive account of object and action selection.

PMID- 19100759
TI  - Perinatal undernutrition-induced obesity is independent of the developmental
      programming of feeding.
AB  - Protein or calorie restriction during gestation and/or suckling induces
      hyperphagia and increases the susceptibility to develop obesity, glucose
      intolerance and hypertension in adulthood. The mechanisms by which early nutrient
      restriction affects the normal physiological regulation of feeding as well as to
      what extent the metabolic programming of hyperphagia contributes to the long-term
      risk of obesity and insulin resistance remain, however, to be determined. Here
      the temporal pattern of food intake and the behavioural satiety sequence were
      investigated in the offspring of Sprague-Dawley rats fed a control (C) or a low
      protein (LP) diet throughout pregnancy and lactation. During the first two months
      of their post-natal life, protein-restricted animals exhibited hyperphagia
      characterized by a delayed appearance of satiety, an increase in meal size and
      reduced latency to eat. Protein-restricted pups also exhibited an enhanced
      expression of the orexigenic peptides Agouti-related protein and neuropeptide Y
      and decreased hypothalamic levels of the anorexigenic peptide pro
      opiomelanocortin. At 8 months, LP rats still consumed larger meals than their
      control counterparts but they ingested daily the same amount of food as control
      offspring and exhibited enhanced abdominal fat and increased levels of
      triglycerides and fatty acids in serum. These observations indicate that the
      hyperphagia observed in young LP rats results from a decreased action of negative
      feedback signals critical to meal termination and an enhanced function of the
      positive signals that initiate and maintain eating. These results also suggest
      that perinatal malnutrition programmes obesity through a mechanism independent of
      its effects on feeding behaviour.

PMID- 19100760
TI  - Suitability of the Neuro-2a cell line for the detection of palytoxin and
      analogues (neurotoxic phycotoxins).
AB  - Palytoxin and related compounds are neurotoxic phycotoxins produced by benthic
      microalgae belonging to the genus Ostreopsis. For several years this family of
      phycotoxins has been posing a threat to human health since they can bioaccumulate
      in shellfish. With the aim of replacing current biological assays, such as the
      mouse or hemolytic assays, we investigated using the Neuro-2a neuroblastoma cell
      line to detect palytoxin and related compounds. Cell death induced by the effects
      of PlTX and analogues on Na+, K+-ATPase were measured using the 1-(4,5
      dimethylthiazol-2-yl)-3,5-diphenylformazan (MTT) assay for mitochondrial
      reductase activity as a surrogate for cell number. The specificity of the Neuro
      2a cell-based assay for palytoxin detection was confirmed by using ouabain, which
      also acts on Na+, K+-ATPase. Pre-treatment of the Neuro-2a cells with ouabain
      minimizes the effects of palytoxin. The specificity of the Neuro-2a assay was
      confirmed by the finding that cell death was not detected when Neuro-2a cells
      were exposed to other phycotoxins with unrelated cellular targets. When the Neuro
      2a assay was used to detect palytoxin in mussel extracts spiked with levels of
      palytoxin around the proposed regulatory value of 250 microg palytoxin/kg
      shellfish, a good correlation was observed between the levels found and the
      expected values. We conclude by proposing an experimental design for functional
      assays using the Neuro-2a cell line for the specific detection of four neurotoxic
      phycotoxin families: saxitoxins, brevetoxins, ciguatoxins and palytoxins.

PMID- 19100761
TI  - The type 4 phosphodiesterase inhibitors rolipram and YM976 facilitate recall of
      the weak version of the passive avoidance task in the day-old chick.
AB  - This series of studies examined the effect of the PDE4 inhibitors rolipram and
      YM976 on the recall of the passive avoidance learning (PAL) task in the day old
      chick, with a particular focus on the role of D1 receptor in activating this
      pathway. The results indicated that 2.0 mg/kg rolipram administered 5 min before
      or immediately, 5, 15 or 30 min following training and 0.025 mg/kg YM976
      administered 15 min before or immediately, 5, or 15 min following training
      facilitated recall of the weak form of the task (i.e. using 20% v/v methyl
      anthranilate (MeA) as the aversant) at 180 min following training. In each case
      the effect emerged from 60 min following the training, and was still observable
      from 180 min to 24 h after training. In addition, whilst administration of 0.5
      mg/kg SCH23390, a D1 receptor antagonist, 10 min prior to training disrupted
      recall for the strong form of the task, co-administration of 2.0 mg/kg rolipram
      but not 0.025 mg/kg YM976 5 min prior to training prevented this disruption
      occurring. The results suggest a role for D1 receptor activation in the processes
      underlying the facilitation of memory by rolipram.

PMID- 19100762
TI  - Human papillomavirus (HPV) awareness and vaccination initiation among women in
      the United States, National Immunization Survey-Adult 2007.
AB  - OBJECTIVES: To report awareness of human papillomavirus (HPV) and HPV vaccine
      among women aged 18-49 years and, for recommended women aged 18-26 years,
      estimate initiation of HPV vaccination and describe factors associated with
      vaccination initiation among a national sample. METHODS: Data were analyzed from
      the National Immunization Survey-Adult, a nationally representative telephone
      survey conducted May-August 2007. Questions were asked about awareness of HPV and
      HPV vaccine and vaccine receipt. RESULTS: A total of 1102 women aged 18-49 years
      were interviewed, 168 were aged 18-26 years. Overall, awareness of HPV (84.3%)
      and of HPV vaccine (78.9%) were high. Among women 18-26 years of age, vaccination
      initiation (> or =1 dose) was 10%. Factors associated with vaccination included
      not being married, living > or =200% of the federal poverty index, having health
      insurance, and vaccination with hepatitis B vaccine. HPV vaccination initiation
      among women aged 27-49 years was 1%. CONCLUSIONS: Awareness of HPV and HPV
      vaccine were high. Two to 5 months after national HPV vaccination recommendations
      were published, one in ten women 18-26 years old had initiated the HPV vaccine
      series. Women at a higher socio-economic level were more likely to receive the
      vaccination. Vaccination initiation and completion will likely increase over the
      next years. Monitoring uptake is important to identify sub-groups that may not be
      receiving the vaccination.

PMID- 19100763
TI  - How methyl cyanide induces aggregation in all-alpha proteins: a case study in
      four albumins.
AB  - Serum albumins are chief carrier of ligands in blood, hence important in clinical
      biotechnology. The effects of methyl cyanide (MeCN), a chief solvent of reverse
      phase chromatography, on four mammalian serum albumins (human, bovine, porcine
      and rabbit sources) were studied at neutral pH with the help of scattering,
      circular dichroism, IR and fluorescence spectroscopy. We have detected an
      intermediate state in the presence of 20% (v/v) MeCN, having 8-9% higher alpha
      helical structure than that of their native states. In the presence of 60% (v/v)
      MeCN another intermediate was observed with non-native beta-sheet structure and
      high tendency to form aggregates.

PMID- 19100764
TI  - The role of crustins in Litopenaeus vannamei in response to infection with shrimp
      pathogens: An in vivo approach.
AB  - Crustin antimicrobial peptides, identified in crustaceans, are hypothesized to
      have both antimicrobial and protease inhibitor activity based on their primary
      structure and in vitro assays. In this study, a reverse genetic approach was
      utilized to test the hypothesis that crustins are antimicrobial in vivo in
      response to bacterial and fungal challenge. Injection of double-stranded RNA
      specific to a 120-bp region of LvABP1, one of the most prominent crustin
      isoforms, yielded a significant reduction in the expression of both crustin mRNA
      and protein within the hemocytes. To test the role of crustins in the shrimp
      immune response, RNAi was first used to suppress crustin expression and animals
      were subsequently injected with low pathogenic doses of either Vibrio penaeicida
      or Fusarium oxysporum. A significant increase in mortality in crustin-depleted
      animals was observed in animals infected with V. penaeicida as compared to
      controls, whereas no significant change in shrimp mortality was observed
      following infection with F. oxysporum.

PMID- 19100765
TI  - Low blood levels of lead and mercury and symptoms of attention deficit
      hyperactivity in children: a report of the children's health and environment
      research (CHEER).
AB  - BACKGROUND: The goal of this study was to examine the association between low
      levels of lead and mercury in blood and symptoms of attention-deficit
      hyperactivity disorder (ADHD) among Korean children. METHODS: One thousand seven
      hundred and seventy eight children at 10 elementary schools in six South Korea
      cities participated in this study. Parents and guardians administered a
      questionnaire including Conners' parents rating ADHD scale to determine the
      presence of ADHD symptoms. In addition, clinical examinations of the children and
      determination of blood lead and mercury levels were included in the first
      Children's Health and Environment Research (CHEER) survey, which is now conducted
      annually in Korea. RESULTS: The risk for the appearance of ADHD symptoms was
      found to increase with the blood lead concentration. The mean blood lead
      concentration was low with a geometric mean of 1.8 microg/dl. The odds ratios
      (95% confidence intervals) for the presence of ADHD symptoms were 1.28 (0.57,
      2.86), 1.32 (0.63, 2.74), 1.65 (0.77, 3.56), and 1.98 (0.76, 5.13) in children
      with blood lead levels of 1-<1.5, -<2.5, -<3.5, and >3.5 microg/dl, compared to
      those with blood lead levels of <1.0 microg/dl; these results statistically
      represented a borderline trend (p for trend: 0.07). The blood lead level showed a
      significant positive association with the Conners' ADHD score (beta=0.50,
      p<0.0001). However, the blood mercury levels were not found to be significantly
      associated with ADHD symptoms in children. The geometric mean mercury
      concentration in the blood was 2.4 microg/l. CONCLUSIONS: The observed
      association between blood lead concentration and the appearance of ADHD symptoms
      in Korean children suggests that lead, even at low concentrations, is a risk
      factor for ADHD.

PMID- 19100767
TI  - Periodic limb movement screening as an additional feature of Emfit sensor in
      sleep-disordered breathing studies.
AB  - BACKGROUND: The standard method for recording periodic limb movements is anterior
      tibialis electromyography (EMG) but other methods are also used. A new movement
      sensor Emfit (ElectroMechanical Film) provides information about sleep-disordered
      breathing but also shows movements in bed. The aim of the study was to
      investigate the usability of a small Emfit sensor in revealing periodic
      movements. METHODS: Twenty seven consecutive patients were studied. Periodic
      movements in EMG and Emfit were scored blindly and periodic leg movement index
      (PLMI) for EMG and periodic movement index (PMI) for Emfit were counted.
      Spearman's correlation coefficient was used to assess the relationship between
      Emfit data and EMG results. Sensitivities and specificities were computed for
      PLMI and PMI levels of 5 and 15 movements/h. Additionally, receiver operating
      characteristic (ROC) curves were derived and the area under the curve (AUC) was
      calculated. RESULTS: The Spearman's correlation coefficient between the PMI of
      Emfit and the PLMI of EMG was 0.87. The sensitivity of the Emfit sensor to detect
      periodic limb movements was 0.91 at the level of 5 movements/h and 0.73 when the
      cut-off level was 15 movements/h. The specificities were 0.75 and 1.00,
      respectively. AUC in ROC analysis was 0.96 and 0.98 in the levels of 5 and 15
      movements/h. CONCLUSIONS: The results suggest that the Emfit sensor might be
      suitable for screening of periodic limb movements even if the sensor is placed
      under the thoracic area of the patient in sleep-disordered breathing studies.

PMID- 19100766
TI  - Physiological and pharmacological implications of beta-arrestin regulation.
AB  - G protein-coupled receptor-targeted drug discovery as well as "compound
      reassessment" requires the utilization of diverse screens to determine agonist
      efficacies and potencies beyond the scope of ligand binding and G protein
      coupling. Such efforts have arisen from extensive studies, both in cellular and
      animal models, demonstrating that these seven transmembrane domain-spanning, G
      protein-coupled receptors may engage in more diverse functions than their name
      suggests and particular focus is drawn to their interactions with beta-arrestins
      (betaarrestins). As regulators, betaarrestins are involved in dampening G protein
      coupling pathways. betaArrestins can also play pro-signaling roles in receptor
      mediated events and the coupling of receptors to betaarrestins may be as
      important as their potential to couple to G proteins in the physiological
      setting. In the last decade, the development of betaarrestin deficient mouse
      models has allowed for the assessment of the contribution of individual
      betaarrestins to receptor function in vivo. This review will discuss the current
      literature that implicates betaarrestins in receptor function in respect to
      physiological and behavioral responses observed in the live animal model.

PMID- 19100768
TI  - Microfluidics and multielectrode array-compatible organotypic slice culture
      method.
AB  - Organotypic brain slice cultures are used for a variety of molecular,
      electrophysiological, and imaging studies. However, the existing culture methods
      are difficult or expensive to apply in studies requiring long-term recordings
      with multielectrode arrays (MEAs). In this work, a novel method to maintain
      organotypic cultures of rodent hippocampus for several weeks on standard MEAs in
      an unmodified tissue culture incubator is described. Polydimethylsiloxane
      (Sylgard) mini-wells were used to stabilize organotypic cultures on glass and MEA
      surfaces. Hippocampus slices were successfully maintained within PDMS mini-wells
      for multiple weeks, with preserved pyramidal layer organization, connectivity,
      and activity. MEAs were used to record the development of spontaneous activity in
      an organotypic cultures for 4 weeks. This method is compatible with integration
      of microchannels into the culture substrate. Microchannels were incorporated into
      the mini-wells and applied to the guidance of axons originating within the slice,
      paving the way for studies of axonal sprouting using organotypic slices.

PMID- 19100769
TI  - Immunostaining for oligodendrocyte-specific galactosphingolipids in fixed brain
      sections using the cholesterol-selective detergent digitonin.
AB  - Galactocerebroside (GalC) and its sulfated derivative sulfatide (SUL) are
      galactosphingolipids abundantly expressed in oligodendrocytes (OLs). Despite
      their biological importance in OL development and function, attempts to visualize
      GalC/SUL in tissue sections have met with limited success. This is at least in
      part because permeabilization of tissue sections with detergents such as Triton X
      100 results in significant degradation of GalC/SUL immunoreactivity. Here we
      establish a novel method that enables visualization of endogenous GalC/SUL in OLs
      and myelin throughout the entire depth of brain sections. We show that treating
      brain sections with the cholesterol-specific detergent digitonin instead of
      Triton X-100 or methanol leads to efficient antibody penetration into tissue
      sections without disrupting GalC/SUL immunoreactivity. We also determine the
      optimal concentrations of digitonin using confocal microscopy. With our method,
      the morphology and the number of GalC/SUL-expressing OLs can be visualized three
      dimensionally. Furthermore, our method is applicable to double immunostaining
      with anti-GalC/SUL antibody and other antibodies which recognize intracellular
      antigens. Our simple method using digitonin should prove to be useful in enabling
      detailed examination of GalC/SUL expression in the brain in both physiological
      and pathological conditions.

PMID- 19100770
TI  - A retrofitted neural recording system with a novel stimulation IC to monitor
      early neural responses from a stimulating electrode.
AB  - Extracellular electrical stimulation is increasingly used for in vitro neural
      experimentation, including brain slices and cultured cells. Although it is
      desirable to record directly from the stimulating electrode, relatively high
      stimulation levels make it extremely difficult to record immediately after the
      stimulation. We have shown that this is feasible by a stimulation system (analog
      IC) that includes the feature of active electrode discharge. Here, we piggybacked
      the new IC onto an existing recording amplifier system, making it possible to
      record neural responses directly from the stimulating channel as early as 3 ms
      after the stimulation. We used the retrofitted recording system to stimulate and
      record from dissociated hippocampal neurons in culture. This new strategy of
      retrofitting an existing system is a simple but attractive approach for
      instrumentation designers interested in adding a new feature for extracellular
      recording without replacing already existing recording systems.

PMID- 19100771
TI  - Allergen-specific immunotherapy.
AB  - Allergy is a significant health problem in industrialized countries and its
      prevalence is continually on the increase: In 1906, when Clemens von Pirquet
      introduced the term "allergy" to describe overwhelming pathological reactions of
      the body caused by contact with antigens, less than 1% of the population were
      affected. Today, more than 25% of the inhabitants of industrialized countries
      suffer from allergic rhinitis, conjunctivitis, asthma, dermatitis or food
      allergies. Allergic symptoms can be alleviated using corticosteroids,
      antihistamines, cromones, decongestants, antimuscarinics or leukotrien
      antagonists. However, only immunotherapy is able to change the course of allergic
      disease and to lead to a long-term improvement which is sustained years after the
      discontinuation of this treatment.

PMID- 19100772
TI  - Influenza: a case for an improved link between vaccine research and public
      health.

PMID- 19100773
TI  - Clinical malaria vaccine development.
AB  - Malaria is a major economic and public health problem in mainly sub-Saharan
      Africa. Globally 300-500 million new infections occur each year with 1-3 million
      fatal cases in particular young children. The most effective way to reduce
      disease and death from infectious diseases is to vaccinate susceptible
      populations. Increasing parasite resistance against available cheap anti-malarial
      drugs urges the need for development of malaria vaccines.

PMID- 19100775
TI  - Prevention of cervical cancer: where immunology meets diagnostics.
AB  - Based on the insight that cervical cancer is caused by high-risk human
      papillomavirus (hrHPV) types, two new directions of cervical cancer prevention
      have emerged: primary prevention by prophylactic vaccination against hrHPV types
      16 and 18, and secondary prevention by cervical screening with HPV DNA testing.
      These "current views" elaborate on both prevention modes in the context of public
      health. It is argued that within the next decades using current vaccines the most
      effective way of prevention and control of cervical cancer requires an integrated
      vaccination-screening approach, including routine prophylactic vaccination to pre
      pubertal women and adapted cervical screening for older women.

PMID- 19100774
TI  - Therapeutic peptide vaccines for treatment of autoimmune diseases.
AB  - Recent advances in immunology have led to exciting new possibilities in medicine.
      We now understand how to design vaccine capable of resetting the balance between
      immune effector and regulatory cells in people suffering from autoimmune and
      allergic diseases. These approaches are effective while avoiding the side effects
      associated with non-specific immune suppression.

PMID- 19100776
TI  - Vaccination immunology: Prevention and beyond: NVVI-Dutch society for immunology
      course Lunteren, 2008, April 3-4.

PMID- 19100777
TI  - Designer adjuvants for enhancing the efficacy of infectious disease and cancer
      vaccines based on suppression of regulatory T cell induction.
AB  - Live attenuated or inactivated bacteria and viruses have formed the basis of many
      successful vaccines, including those that have eliminated smallpox and have
      almost eliminated poliovirus. The whole virus or bacteria approach remains the
      most effective means of generating protective immunity by vaccination. However,
      these vaccines can be associated with mild to severe side effects, such as that
      observed with the whole cell pertussis vaccine. Furthermore, rare cases of
      vaccine-associated disease can result from reversion of an attenuated virus to
      the virulent form, such as that reported with the oral polio vaccine. Advances in
      genomics, molecular biology and immunology have now facilitated the
      identification, recombinant expression and immunological characterization of
      protective antigens from infectious organisms, permitting a more rational
      approach to vaccine design. Purified native or recombinant proteins or
      polysaccharides (linked to carrier proteins) now provide a much cleaner, safer
      and more immunologically defined alternative to live or killed whole cell
      vaccines. However, these subunit vaccines lack the danger signals required to
      activate innate immune responses and must therefore be delivered with potent
      adjuvants or delivery systems in order to generate protective adaptive immune
      responses.

PMID- 19100778
TI  - Principles of vaccination and possible development strategies for rational
      design.
AB  - Historically, apart from hygiene, vaccination can be considered as one of the
      most successful accomplishments of public health in the 20th century. It has lead
      to some of the greater public health triumphs ever, including the eradication of
      naturally occurring smallpox and in the control of diseases such as polio. In
      addition there has been a significant reduction in disease burden imposed by
      measles, mumps, hepatitis, influenza, diphtheria, haemophilus influenza B and
      many other infections.

PMID- 19100779
TI  - Influenza vaccines: the virosome concept.
AB  - Influenza virosomes are virus-like particles, which retain the cell binding and
      membrane fusion properties of the native virus, but lack the viral genetic
      material. These functional characteristics of influenza virosomes form the basis
      for their immunogenicity. First, the repetitive arrangement of the major viral
      envelope glycoprotein, haemagglutinin, on the virosomal surface mediates a co
      operative interaction with Ig receptors on B lymphocytes, stimulating strong
      antibody responses. In addition, virosomes interact efficiently with antigen
      presenting cells, such as dendritic cells, resulting in activation of T
      lymphocytes and induction of a balanced Th1/Th2 response. Also, as a result of
      fusion of the virosomes with the endosomal membrane, virosome-encapsulated
      antigens gain access to the MHC class I presentation pathway, thus priming
      cytotoxic T lymphocyte (CTL) activity. Finally, virosomes represent an excellent
      platform for inclusion of lipophilic adjuvants for further improvement of the
      quality and quantity of virosome-induced immune responses.

PMID- 19100780
TI  - Rapid synchronization of hepatitis C virus infection by magnetic adsorption.
AB  - Hepatitis C virus (HCV) entry into target cells is thought to be a multistep
      process involving several cellular factors. However, their precise role during
      virus entry is unclear. Investigation of the mechanisms of HCV entry, such as the
      order of intervention by the cellular receptors, requires synchronizing
      infections. This study describes a new method involving magnetic adsorption of
      virus to nanoparticles to synchronize infection, which can be adapted to both HCV
      pseudoparticles and cell culture infectious HCV. By combining these particles
      with negatively or positively charged magnetic nanoparticles it was possible to
      adsorb them onto target cells under a magnetic field in only 2min. This resulted
      in greater efficiency of virus adsorption to cells, and increased the infectivity
      of cell culture infectious virus, as compared to the standard protocol involving
      incubation of the virus with cells at 4 degrees C for 1h, or to a standard
      infection at 37 degrees C. Furthermore, magnetic adsorption respected the natural
      entry route of the virus, making this system suitable to study the early stages
      of HCV infection.

PMID- 19100781
TI  - Fast and slow brain rhythms in rule/expectation violation tasks: focusing on
      evaluation processes by excluding motor action.
AB  - Theta rhythm has been connected to ERP components such as the error-related
      negativity (ERN) and the feedback-related negativity (FRN). The nature of this
      theta activity is still unclear, that is, whether it is related to error
      detection, conflict between responses or reinforcement learning processes. We
      examined slow (e.g., theta) and fast (e.g., gamma) brain rhythms related to rule
      violation. A time-frequency decomposition analysis on a wide range of frequencies
      band (0-95 Hz) indicated that the theta activity relates to evaluation processes,
      regardless of motor/action processes. Similarities between the theta activities
      found in rule-violation tasks and in tasks eliciting ERN/FRN suggest that this
      theta activity reflects the operation of general evaluation mechanisms. Moreover,
      significant effects were found also in fast brain rhythms. These effects might be
      related to the synchronization between different types of cognitive processes
      involving the fulfillment of a task (e.g., working memory, visual perception,
      mathematical calculation, etc.).

PMID- 19100782
TI  - Variation in brain lateralization during various language tasks: a functional
      transcranial Doppler study.
AB  - Language dominance has repeatedly been demonstrated by means of functional
      transcranial Doppler (fTCD) ultrasonography. However, one strongly lateralizing
      paradigm might be an overestimation of overall language lateralization. We
      hypothesized that significant differences between hemodynamic patterns could be
      shown by using multiple language functions (such as productive and receptive
      tasks). Particularly, we expected more left-hemispheric activity in frontal and
      productive tasks and we expected less clear left-hemispheric activity in temporal
      regions and receptive tasks. Thirty healthy volunteers were included in the
      study. The lateralization index (LI) was measured with transcranial Doppler
      ultrasonography for each subject during four language tasks: a cued word
      generation task (WF), a sentence construction task (SENT), a reading task (READ),
      and a semantic decision task (SEMANT). Left-hemispheric dominance was found in
      90%, 80%, 73.3% and 66.7% of the subjects for respectively WF, SENT, READ and
      SEMANT. A repeated measures analysis of variance revealed significant differences
      in LIs between the different language tasks (p<.01). Our results showed that
      productive and syntactic tasks (WF and SENT) lateralize stronger than receptive
      tasks (READ and SEMANT). The use of a variety of language tasks in the
      determination of language lateralization therefore appears to be essential in
      providing a more comprehensive view of language functioning.

PMID- 19100783
TI  - Simulated weightlessness aggravates hypergravity-induced impairment of learning
      and memory and neuronal apoptosis in rats.
AB  - It has been demonstrated that altered gravity may lead to impairments in
      cognitive functions. However, the effect of a combination of hypergravity and
      weightlessness on cognitive functions is not well understood. In the present
      study, we report the effects of high sustained hypergravity after 7 days'
      simulated weightlessness on learning and memory abilities and neuronal apoptosis
      in rats. In the Y-maze tests, hypergravity (HG) or simulated weightlessness (SW)
      significantly decreases accuracy, and increases reaction time of rats compared to
      that of controls. On the contrary, in the passive avoidance test, HG or SW
      treatment significantly shortens latency and prolongs total time compared to
      those of controls. In addition, TUNEL staining shows a few apoptotic cells in
      cortex and hippocampus in the HG, SW and HG+SW groups, and the number of TUNEL
      positive cells was found to be the most in the HG+SW group. Furthermore, rats
      with combined HG and SW treatment reveal a synergistic effect in both the Y-maze
      and the passive avoidance tests, as well as increased neuronal cell death. These
      findings suggest that simulated weightlessness may exacerbate hypergravity
      induced impairment of learning and memory, likely caused by neuronal cell death
      in rats.

PMID- 19100785
TI  - Evaluation of new leptin fragments on food intake and body weight of normal rats.
AB  - Leptin, a protein hormone originating from adipose tissue, circulates in the
      plasma and affects the energy balance by interacting with the hypothalamus.
      Leptin plays an important role in the regulation of a variety of physiological
      functions, including food intake, body temperature and body weight maintenance.
      Tertiary structure of the leptin molecule reveals the existence of a four-helix
      bundle that is characteristic of the short-helix cytokines. To identify regions
      of the leptin molecule responsible for its bioactivity, we have recently
      synthesized six peptides based on the protein three-dimensional structure. Our
      results indicated that the fragments Ac-hLEP(92-115)-NH(2) (IV) and Ac-[Ser(117)]
      hLEP(116-140)-NH(2) (V) were recognized by leptin receptor present in hp-75 cells
      validating that this region of the molecule contain the functional epitope of the
      leptin molecule. In the present study, a new series of decapeptides encompassing
      the region of fragments IV and V of leptin were synthesized, and their effects on
      body weight and food intake were assessed when administered into the lateral
      cerbroventricle of normal rats. Peptides were synthesized by SPPS, purified by RP
      HPLC and characterized by LC/ESI-MS. We also performed a conformational study of
      the peptides by circular dichroism in order to correlate the biological activity
      and secondary structure of the leptin fragments. Among the fragments tested, we
      found that Ac-hLEP(110-119)-NH(2) (VI) induce a significant reduction in both
      body weight and food intake. The use of synthetic leptin-derivate fragments may
      offer the basis for the development of compounds with potential application in
      human obesity or to its related metabolic dysfunctions.

PMID- 19100786
TI  - Findings of P300-like and CNV-like potentials in rat model of depression
      following repeatedly forced swim stress.
AB  - The aim of this study was to explore whether there were abnormalities of CNV-like
      and P(300)-like potentials in stressed rats following repeatedly forced swim
      stress. Forty male rats were randomly divided into 4 groups: the control groups
      (Control-1 and Control-2) and the stressed groups (Stress-1 and Stress-2). Rats
      in stressed groups were administered to repeatedly forced swim 7 or 14 days
      respectively. Body weight gain, saccharin preference test and open field test
      were performed. After being anesthetized with urethane, P(300)-like potentials
      were evoked by the oddball auditory stimulation and CNV-like potentials were
      elicited by condition-test stimulus. Results of behavioral tests displayed less
      body weights and less saccharine solution intake in stressed rats and significant
      effects of stress on the number of crossing squares, the duration of rearing and
      the number of grooming in open field test. Prolonged P3 latencies and decreased
      P3 amplitudes of P(300)-like potentials were found in the stressed rats. CNV
      amplitudes were lower in the stressed rats than those in control. Moreover, there
      were significant correlations between parameters of ERPs (including P3 latency,
      amplitude and CNV amplitude) and a serial of behavioral traits. This study
      provides an important evidence of changes of CNV-like and P(300)-like potentials
      in depressed rats following repeatedly forced swim stress. Based on this study,
      ERPs should be taken into consideration and applied as the useful tools in the
      research work of depressed animal models.

PMID- 19100787
TI  - On the relationship between interoceptive awareness and the attentional
      processing of visual stimuli.
AB  - Mental processes related to visceral activity have gained growing interest during
      the last few years. The following study is the first to investigate possible
      interactions between interoceptive awareness and measures of attentional
      performance. We tested the hypothesis whether interoceptive awareness is
      positively related to indices of selective and divided attentional performances.
      Using a heartbeat perception task, 29 healthy female participants were separated
      into two groups scoring either high or low in an interoceptive awareness task.
      Attentional performance was assessed by several tests including the 'd2 test of
      attention' and subtests from the 'TAP: Test Battery for Attentional Performance'.
      We observed a significantly better performance in selective and divided attention
      for participants with high interoceptive awareness. Our data suggests that
      interoceptive awareness is related to a better performance especially in tasks
      assessing selective and divided attention. We conclude 1) that perception of
      bodily states might be a crucial determinant for the processing of external,
      visual stimuli, 2) that the ability to perceive internal signals might be an
      indicator of self-focused attention, and 3) that bodily signals may use, at least
      in part, similar processing resources as signals from the attention system.

PMID- 19100784
TI  - The neonatal ventral hippocampal lesion as a heuristic neurodevelopmental model
      of schizophrenia.
AB  - Traditionally, animal models of schizophrenia were predominantly pharmacological
      constructs focused on phenomena linked to dopamine and glutamate neurotransmitter
      systems, and were created by direct perturbations of these systems. A number of
      developmental models were subsequently generated that allowed testing of
      hypotheses about the origin of the disease, mimicked a wider array of clinical
      and neurobiological features of schizophrenia, and opened new avenues for
      developing novel treatment strategies. The most thoroughly characterized
      (approximately 100 primary research articles) is the neonatal ventral hippocampal
      lesion (NVHL) model, which is the subject of this review. We highlight its
      advantages and limitations, and how it may offer clues about the extent to which
      positive, negative, cognitive, and other aspects of schizophrenia, including
      addiction vulnerability, represent inter-related pathophysiological mechanisms.

PMID- 19100789
TI  - Family- and population-based association studies of monoamine oxidase A and
      autism spectrum disorders in Korean.
AB  - Monoamine oxidase A gene (MAOA) has been thought to be a candidate gene
      implicated in autism spectrum disorder (ASD). This study evaluates the
      relationship between ASDs and MAOA markers (i.e., uVNTR and four single
      nucleotide polymorphisms (SNPs)) in 151 Korean family trios with children
      diagnosed with ASDs, and 193 unrelated Korean controls. The result of case
      control global haplotype analysis also showed a statistically significant
      difference in haplotype frequencies between ASD patients and controls (male
      d.f.=5, p<0.001; female d.f.=7, p<0.001). With the specific haplotype analyses,
      the frequencies of the most frequent haplotype (AGG) with three SNPs
      (rs5906883+rs1137070+rs3027407) in ASD showed significant statistical differences
      between ASD patients and controls in both the male and female groups (d.f.=1,
      male p=0.001, female p<0.001). In a family-based association test (FBAT)
      analysis, it was observed that, in the dominant model, a three-repeat allele of a
      MAOA-uVNTR marker was preferentially transmitted in ASDs (Z=2.213, p=0.027).
      Moreover, in the global haplotype analysis, the statistically significant
      evidence of associations with ASD were demonstrated in additive and dominant
      models (additive chi(2)=11.349, d.f.=2, p=0.003; dominant chi(2)=6.198, d.f.=2,
      p=0.045).

PMID- 19100788
TI  - Activation of c-Jun-N-terminal kinase in a rat model of intracerebral hemorrhage:
      the role of iron.
AB  - Iron accumulates in the brain and contributes to brain injury after intracerebral
      hemorrhage (ICH). The c-Jun-N-terminal kinase (JNK) signaling pathway mediates
      cell death after ischemic stroke, however, the involvement of JNK in ICH is not
      well known. This study investigated whether the JNK signaling pathway is
      activated by iron after ICH. Male Sprague-Dawley rats received an infusion of
      autologous whole blood (as a model of ICH) or ferrous iron into the right basal
      ganglia and control rats had an infusion of saline. Some ICH rats were treated
      with either deferoxamine (DFX), an iron chelator, or vehicle. Activation of JNK
      was measured by Western blot analysis and immunohistochemistry. Free iron in
      cerebrospinal fluid (CSF) and behavioral outcomes following ICH were also
      examined. We found that activated JNK in the brain were increased after ICH, and
      an intracerebral infusion of ferrous iron also upregulated brain activated JNK.
      Free iron accumulated in CSF and systemic administration of DFX after ICH reduces
      free iron contents in CSF, suppresses JNK activation and improves ICH-induced
      neurological deficits. Our results demonstrated that the JNK signaling pathway is
      activated after ICH and iron may contribute to this activation. DFX reduces free
      iron levels and attenuates activation of JNK suggesting iron chelation may be
      useful therapy for ICH patients.

PMID- 19100790
TI  - Bombyx mori nucleopolyhedrovirus FP25K is essential for maintaining a steady
      state level of v-cath expression throughout the infection.
AB  - It has been previously reported that the fp25K product of Bombyx mori
      nucleopolyhedrovirus (BmNPV) is required for post-mortem host degradation, but
      the mechanism by which it regulates host degradation is still unknown. This study
      shows that disruption of BmNPV fp25K attenuates the expression of viral cathepsin
      gene (v-cath) at a late stage of infection, and thus reduces the secretion of its
      product V-CATH. Western blot analysis showed that secretion of V-CATH was
      severely reduced in BmN cells and B. mori larvae infected with Bm25KD, a BmNPV
      mutant lacking functional fp25K, compared to that of wild-type BmNPV. Also,
      reduced accumulation of pro-V-CATH in Bm25KD-infected cells was observed from 4
      days postinfection (dpi), during which V-CATH was first detected in the medium of
      BmNPV-infected cells. qRT-PCR experiments showed that the expression levels of v
      cath mRNA in wild-type- and Bm25KD-infected BmN cells were comparable at 3 dpi,
      but showed a marked decrease in Bm25KD-infected BmN cells at 4 dpi. Collectively,
      these results suggest that BmNPV FP25K is essential for the proper
      transcriptional regulation of v-cath and efficient secretion of V-CATH, and a
      steady-state level of v-cath expression during the period of V-CATH secretion
      (after 4 dpi) is required for post-mortem host degradation.

PMID- 19100791
TI  - Mutagenesis identifies the critical regions and amino acid residues of suid
      herpesvirus 1 DNA-binding protein required for DNA binding and strand invasion.
AB  - Herpesviral DNA-binding protein (DBP) is a unique protein involved in viral DNA
      replication and genomic recombination. It binds and stabilizes the single
      stranded DNA. It also forms the D-loops and promotes the strand invasion. To
      identify the functional regions and amino acid residues required for DNA binding
      and D-loop formation, we characterized several DBP mutants of suid herpesvirus 1
      (SuHV-1). Acetic anhydride modification assay showed that lysine residues were
      critical for DNA binding and D-loop formation. Replacement of highly conserved
      lysine residues with alanine revealed that Lys-756 and Lys-970 were critical for
      DNA binding, while Lys-161 participated in DNA binding and D-loop formation.
      Analysis of nested deleted mutants showed that N-terminal 201 amino acid residues
      and C-terminal 305 amino acid residues were required for D-loop formation and DNA
      binding, respectively. In conclusion, these findings suggested that SuHV-1 DBP
      contained critical regions for DNA binding and D-loop formation, and Lys-161, Lys
      756, and Lys-970 were required for DNA binding or D-loop formation.

PMID- 19100792
TI  - Identification of Taiwan and China-like recombinant avian infectious bronchitis
      viruses in Taiwan.
AB  - Infectious bronchitis virus (IBV) infections in poultry cause great economic
      losses to the poultry industry worldwide. The emergence of viral variants
      complicates disease control. The IBV strains in Taiwan were clustered into two
      groups, Taiwan group I and Taiwan group II, based on the S1 gene. A variant was
      previously identified and showed a distinct S1 gene homology with other local
      strains. This study investigated the 3' 7.3 kb genome of eight Taiwan strains
      isolated from 1992 to 2007. The genes of interest were directly sequenced.
      Sequence analyses were performed to detect any recombination event among IBVs.
      The results demonstrated that all of the examined viruses maintained the typical
      IBV genome organization as 5'-S-3a-3b-E-M-5a-5b-N-UTR-3'. In the phylogenetic
      analyses, various genes from one strain were clustered into separate groups.
      Moreover, frequent recombination events were identified in the Simplot analyses
      among the Taiwan and China CK/CH/LDL/97I-type strains. Putative crossover sites
      were located in the S1, S2, 3b, M genes and the intergenic region between the M
      and 5a genes. All of the recombinants showed chimeric IBV genome arrangements
      originated from Taiwan and China-like parental strains. Field IBVs in Taiwan
      undergo genetic recombination and evolution.

PMID- 19100793
TI  - Single amino acid substitution in the methyltransferase domain of Paprika mild
      mottle virus replicase proteins confers the ability to overcome the high
      temperature-dependent Hk gene-mediated resistance in Capsicum plants.
AB  - Capsicum plants harboring the Hk gene (Hk) show resistance to Paprika mild mottle
      virus (PaMMV) at 32 degrees C but not 24 degrees C. To identify the viral
      elicitor that activates the Hk-mediated resistance, several chimeric viral
      genomes were constructed between PaMMV and Tobacco mosaic virus-L. Infection
      patterns of these chimeric viruses in Hk-harboring plants revealed responsibility
      of PaMMV replicase genes for activation of the Hk-mediated resistance. The
      comparison of nucleotide sequence of replicase genes between PaMMV and PaHk1, an
      Hk-resistance-breaking strain of PaMMV, revealed that the adenine-to-uracil
      substitution at the nucleotide position 721 causes an amino acid change from
      threonine to serine at the 241st residue in the methyltransferase domain.
      Introduction of the A721U mutation into the replicase genes of parental PaMMV
      overcame the Hk resistance at 32 degrees C. The results indicate that Hk-mediated
      resistance is induced by PaMMV replicase proteins and that methyltransferase
      domain has a role in this elicitation.

PMID- 19100794
TI  - Porous nano-HA/collagen/PLLA scaffold containing chitosan microspheres for
      controlled delivery of synthetic peptide derived from BMP-2.
AB  - It is advantageous to incorporate controlled growth factor delivery into tissue
      engineering strategies. The purpose of the present study was to develop a novel
      tissue engineering scaffold with the capability of controlled releasing BMP-2
      derived synthetic peptide. Porous nano-hydroxyapatite/collagen/poly(L-lactic
      acid)/chitosan microspheres (nHAC/PLLA/CMs) composite scaffolds containing
      different quantities of chitosan microspheres (CMs) were prepared by a thermally
      induced phase separation method. Dioxane was used as the solvent for PLLA.
      Introduction of less than 30% of CMs (on PLLA weight basis) did not remarkably
      affect the morphology and porosity of the nHAC/PLLA/CMs scaffolds. However, as
      the microspheres contents increased to 50%, the porosity of the composite
      decreased rapidly. The compressive modulus of the composite scaffolds increased
      from 15.4 to 25.5 MPa, while the compressive strength increased from 1.42 to 1.63
      MPa as the microspheres contents increased from 0% to 50%. The hydrolytic
      degradation and synthetic peptide release kinetics in vitro were investigated by
      incubation in phosphate buffered saline solution (pH 7.4). The results indicated
      that the degradation rate of the scaffolds was increased with the enhancement of
      CMs dosage. The synthetic peptide was released in a temporally controlled manner,
      depending on the degradation of both incorporated chitosan microspheres and PLLA
      matrix. In vitro bioactivity assay revealed that the encapsulated synthetic
      peptide was biologically active as evidenced by stimulation of rabbit marrow
      mesenchymal stem cells (MSCs) alkaline phosphatase (ALP) activity. The successful
      microspheres-scaffold system offers a new delivery method of growth factors and a
      novel scaffold design for bone regeneration.

PMID- 19100795
TI  - Nucleic acid delivery with chitosan and its derivatives.
AB  - Chitosan is a naturally occurring cationic mucopolysaccharide. It is generally
      biocompatible, biodegradable, mucoadhesive, non-immunogenic and non-toxic.
      Although chitosan is able to condense nucleic acids (NA) (both DNA and RNA) and
      protect them from nuclease degradation, its poor water solubility and low
      transfection efficacy have impeded its use as an NA carrier. In order to overcome
      such limitations, a multitude of strategies for chitosan modification and
      formulation have been proposed. In this article, we will first give a brief
      overview of the physical and biological properties of chitosan. Then, with a
      special focus on plasmid DNA delivery, we will have a detailed discussion of the
      latest advances in chitosan-mediated NA transfer. For future research, the
      following three important areas will be discussed: chitosan-mediated therapeutic
      small RNA transfer, structure-activity relationships (SAR) in chitosan vector
      design, and chitosan-mediated oral/nasal NA therapy.

PMID- 19100796
TI  - Extrudable core system: development of a single-layer osmotic controlled-release
      tablet.
AB  - A new controlled-release, extrudable core system (ECS) tablet has been developed
      which osmotically delivers high doses of low solubility active pharmaceutical
      ingredients (API's). The tablet has a single core formed in a modified oval shape
      with a semi-permeable coating. The core contains hydroxyethylcellulose, which
      serves to entrain the API particles as they are extruded out a hole in the
      coating at one end of the tablet, and a sugar, which provides the osmotic driving
      force for water imbibing. The dosage form has been successfully shown to control
      delivery of API over a range of delivery rates even with 50% of the tablet being
      API (up to about 500 mg).

PMID- 19100797
TI  - Pharmacokinetics and pharmacogenomics in breast cancer chemotherapy.
AB  - Locally advanced or metastatic breast cancer is typically treated with
      chemotherapy. Multiple combinations of chemotherapy regimens are available,
      including anthracyclines, taxanes, antimetabolites, alkylating agents, platinum
      drugs and vinca alkaloids. This review discusses the pharmacokinetic and
      pharmacogenomic information available for commonly used breast cancer
      chemotherapy drugs. Pharmacogenomic associations for many drugs have yet to be
      identified or validated in breast cancer. Further work is needed to identify
      markers to screen breast cancer patients prior to therapy selection.

PMID- 19100798
TI  - Inter-meal interval is increased in mice fed a high whey, as opposed to soy and
      gluten, protein diets.
AB  - This study aimed to characterise meal patterns and satiety effects of diets that
      are high in protein but differ in protein source. Using a computerised automatic
      recording system, meal pattern behaviour was recorded continuously for 7 days in
      mice fed single (whey, soy or gluten) or different combined protein diets.
      Overall, average energy intake was significantly lower in mice fed a whey protein
      diet than those fed soy, gluten and lab chow diets. Among these four diets, the
      inter-meal interval of mice fed a whey protein diet was the longest and their
      meal number was the lowest. Combination of whey and gluten caused a lower energy
      intake, longer inter-meal interval and lower meal number compared to the other
      paired combinations. A significant interaction effect between whey and gluten was
      found for the reduction of energy intake and meal number. In conclusion, this
      study showed that the whey protein diet had the most potent satiety effect (inter
      meal), but no difference in satiation effect (intra-meal) compared with the other
      dietary proteins tested. Combination of whey and gluten in a high protein diet
      may be a better formula than other combinations to provide a satiety effect and
      suppress energy intake for antiobesity purposes.

PMID- 19100799
TI  - Chronic elevation of extracellular glutamate due to transport blockade is
      innocuous for spinal motoneurons in vivo.
AB  - Glutamate-mediated excitotoxicity has been considered to play an important role
      in the mechanism of spinal motoneuron death in amyotrophic lateral sclerosis
      (ALS), and some reports suggest that this excitotoxicity may be due to a
      decreased glutamate transport and the consequent elevation of its extracellular
      level. We have previously shown that short lasting increments in extracellular
      glutamate due to administration of the non-selective glutamate transport blocker
      l-2,4-trans-pyrrolidine-dicarboxylate (PDC) by microdialysis in the rat spinal
      cord do not induce motoneuron damage. In the present work we examined the
      potential involvement of chronic glutamate transport blockade as a causative
      factor of spinal motoneuron death and paralysis in vivo. Using osmotic minipumps,
      we infused directly in the spinal cord for up to 10 days PDC and another
      glutamate transport blocker, dl-threo-beta-benzyloxyaspartate (TBOA), and we
      measured by means of microdialysis and HPLC the extracellular concentration of
      glutamate and other amino acids. We found that after the infusion of both PDC and
      TBOA the concentration of endogenous extracellular glutamate was 3-4-fold higher
      than that of the controls. Nevertheless, in spite of this elevation no motoneuron
      degeneration or gliosis were observed, assessed by histological examination and
      choline acetyltransferase and glial fibrillary acidic protein
      immunocytochemistry. In accord with this lack of toxic effect, no motor deficits,
      assessed by three motor activity tests, were observed. Because we had previously
      shown that under identical experimental conditions the infusion of alpha-amino-3
      hydroxy-5-methyl-4-isoxazole propionate (AMPA) induced progressive motoneuron
      death and paralysis, we conclude that prolonged elevation of extracellular
      glutamate due to its transport blockade in vivo is innocuous for spinal
      motoneurons and therefore that these results do not support the hypothesis that
      glutamate transport deficiency plays a crucial role as a causal factor of spinal
      motoneuron degeneration in ALS.

PMID- 19100800
TI  - Ketogenic diet is antiepileptogenic in pentylenetetrazole kindled mice and
      decrease levels of N-acylethanolamines in hippocampus.
AB  - The ketogenic diet (KD) is used for the treatment of refractory epilepsy in
      children, however, the mechanism(s) remains largely unknown. Also, the
      antiepileptogenic potential in animal models of epilepsy has been poorly
      addressed. Activation of cannabinoid type-1 receptor (CB(1)-R) upon seizure
      activity may mediate neuroprotection as may several N-acylethanolamines. It is
      unknown how the KD interfere with the endocannabinoid system. We investigated the
      antiepileptogenic potential of the KD in the pentylenetetrazole kindling model in
      young mice and measured the hippocampal levels of CB(1)-R by Western blot and of
      endocannabinoids and N-acylethanolamines by mass spectrometry. The KD
      significantly decreased incidence and severity of seizures, and significantly
      increased the latency to clonic convulsions. There were no changes in levels of
      endocannabinoids or CB(1)-R expression by either seizure activity or type of
      diet. The level of oleoylethanolamide as well as the sum of N-acylethanolamines
      were significantly decreased by the KD, but were unaffected by seizure activity.
      The study shows that the KD had clear antiepileptogenic properties in the
      pentylenetetrazole kindling model and does not support a role of endocannabinoids
      in this model. The significance of the decreased hippocampal level of
      oleoylethanolamide awaits further studies.

PMID- 19100801
TI  - Augmented chemokine levels and chemokine receptor expression on immune cells
      during pulmonary tuberculosis.
AB  - The systemic changes in immune mediators such as cytokine and chemokines, and
      their synchronized interaction that regulates the cell trafficking during
      Mycobacterium tuberculosis (M. tuberculosis) infection, were studied. Cytokines
      and chemokines were evaluated by cytometric bead array (CBA) and enzyme-linked
      immunosorbent assay (ELISA) in 34 pulmonary tuberculosis (PTB) patients and 30
      healthy subjects. The expression of chemokine receptors was assessed by flow
      cytometry. A significant increase in IP-10, MIG, interleukin-8, RANTES, and
      interleukin-6 levels was found, whereas a decrease in interferon-gamma, tumor
      necrosis factor-alpha, and transforming growth factor-beta was observed during
      PTB. Significant correlation within chemokines and between cytokines was observed
      in PTB. All immune cells except monocytes and B cells expressed significantly
      higher levels of CCR1, CCR2, and CXCR2 whereas CCR7 expression was upregulated
      only on monocytes and neutrophils in PTB. Both T and B cells expressed
      significantly high levels of CXCR3 which also correlated well with the chemokine
      levels in PTB. Thus, it was found that chemokines function coordinately and
      consistently during PTB. This balanced chemokine and cytokine relationship at the
      periphery may aid in amplified effector immune cell trafficking and retarded
      monocyte migration through differential chemokine receptor expression.

PMID- 19100802
TI  - Raising allo-restricted cytotoxic T lymphocytes by co-culture of murine
      splenocytes with autologous macrophage bearing the peptide/allo-major
      histococompatibility complex.
AB  - Generation and adoptive transfusion of alloreactive cytotoxic T lymphocytes
      (CTLs) specific for tumor are expected to circumvent tumor tolerance. Here we
      describe a novel protocol to raise allo-restricted, peptide-specific CTLs by co
      culture of murine splenocytes and autologous macrophage bearing an allogeneic H
      2K molecule associated with its restricted peptide (peptide/allo-MHC). The
      extracellular domains of H-2K(d) were fused with constant domains of murine IgG2a
      heavy chain to generate a fusion protein (peptide/H-2K(d)/IgG2aFc, the dimer)
      consisting of divalent TCR-ligands and an IgG Fc receptor type I (FcgammaRI)
      reactive moiety. The dimer is able to bind to macrophage (Mvarphi) of H-2K(k) via
      the interaction of the Fc part with FcgammaRI, and cause the H-2K(k) Mvarphi to
      be coated with the peptide/H-2K(d) complex. The results show that proliferation
      of CD8+ cells is enhanced and that the specific-tetramer stained CD8+ cells
      appear more frequently by co-culture of H-2K(k) splenocytes with the autologous
      Mvarphi loaded with the dimer. Furthermore, the CD8+ T cells from the co-cultural
      bulk exhibit an elevated cytotoxicity against a specific target (H-2K(d)
      restricted, peptide-specific cytotoxicity), compared with that against the
      irrelevant targets. This study provides a strategy for preparation of allo
      restricted, peptide-specific CTLs, which may add to our arsenal for adoptive
      immunotherapy to eliminate chronic virally infected or tumor cells.

PMID- 19100803
TI  - Physicians' experiences with HPV vaccine delivery: evidence from developing
      country with multiethnic populations.
AB  - Physicians' experiences in providing human papillomavirus (HPV) immunization were
      assessed by mailed questionnaire. Response rate of 41.4% was achieved. Malay
      Muslim physicians were more likely to agree that cultural sensitivity is an issue
      when recommending HPV vaccines. Pediatricians and family physicians were more
      likely to agree that acceptance is better if vaccines were recommended to prevent
      cervical cancer than to prevent a sexually transmitted disease. Near 70% rated
      success of HPV vaccines recommendation in their practice as very poor with the
      majority patients preferred to postpone immunization. Physicians reported
      cultural disparities in vaccine uptake and perceived high vaccination cost limits
      its use.

PMID- 19100804
TI  - Immunological evaluation in nonhuman primates of formulations based on the
      chimeric protein P64k-domain III of dengue 2 and two components of Neisseria
      meningitidis.
AB  - The main problem in the development of successful vaccines against dengue based
      on recombinant proteins is the necessity to use potent adjuvants to reach a
      proper functional immune response. Our group reported the expression,
      characterization and immunological evaluation of the recombinant protein PD5,
      which contains the domain III of the Envelope protein from dengue 2 virus fused
      to the carrier protein P64k. This construct completely protected monkeys against
      viral challenge when the Freund's adjuvant was employed. Therefore, to define
      suitable formulations for human use, the present work relies on the evaluation of
      PD5, produced with a high purity and under GMP conditions, when formulated either
      with outer membrane vesicles (OMV) or the serogroup A capsular polysaccharide
      (CPS-A) from Neisseria meningitidis, both adsorbed on aluminium hydroxide. The
      antibody response to the formulation containing the CPS-A was clearly superior to
      that of the formulation with OMV. The experiment of in vivo protection supported
      this evidence, since only the group immunized with PD5 and CPS-A was partially
      protected upon viral challenge. This is the first study in which the
      polysaccharide A of N. meningitidis is successfully employed as adjuvant for
      viral antigens.

PMID- 19100805
TI  - Comparison of Montanide adjuvants, IMS 3012 (Nanoparticle), ISA 206 and ISA 35
      (Emulsion based) along with incomplete Freund's adjuvant for hyperimmunization of
      equines used for production of polyvalent snake antivenom.
AB  - The use of adjuvant is of fundamental importance in vaccines formulations and
      antisera production. Currently selection and use of adjuvant systems in snake
      antivenom preparation has become a major issue in terms of animal welfare as well
      as economics. In order to minimize disadvantages associated with traditionally
      used Freund's adjuvant (FA) in equines and to produce potent polyvalent antivenom
      against four Indian snake venoms in minimum possible period, a comparison was
      made between various commercially available non-emulsion/emulsion based adjuvants
      like IMS 3012, ISA 206 and ISA 35 with Incomplete Freund's adjuvant (IFA) for
      their immunopotentiation capacity and safety in donor animals. The present study
      was conducted in 33 new horses, randomly divided into four groups and
      hyperimmunized using crude mixture of snake venoms, viz.; Cobra venom (CV),
      Russell's viper venom (RV), Krait venom (KV) and Saw-scaled viper (EV) along with
      four above mentioned adjuvants through subcutaneous (s.c.) route at intervals of
      two weeks. Periodic standard safety assessments were done. Immunopotentiation
      ability of each adjuvant group in terms of percent responders were estimated at
      14th, 21st, 30th and 43rd week. The neutralization activity (ED(50)) of pooled
      sera samples by 43(rd) week, obtained with IMS 3012 group for CV, RV, KV and EV
      venoms were 0.133, 0.143, 0.070 and 0.270 mg venom/ml of serum respectively. The
      antivenom potency with IMS 3012 and overall responding horses (100%) even against
      weak immunogen like CV was significantly higher (p<0.05) than other three
      adjuvants studied. The horses of IMS 3012 group showed minimum local reactions at
      injection site, while horses from other three groups exhibited moderate (++)
      reactions; 66.7% in ISA 206, 12.5% in ISA 35 and 14.3% in IFA respectively,
      however these were transient and reabsorbed or healed subsequently. Finally, we
      conclude that, nanoparticle adjuvant IMS 3012 could be a possible alternative to
      the emulsion adjuvants for primary phase of immunization in antivenom preparation
      considering its better immunopotentiation capacity and safety in donor animals.

PMID- 19100806
TI  - Plant-derived hemagglutinin protects ferrets against challenge infection with the
      A/Indonesia/05/05 strain of avian influenza.
AB  - The global spread of highly pathogenic avian influenza virus (H5N1 subtype) has
      promoted efforts to develop human vaccines against potential pandemic outbreaks.
      However, current platforms for influenza vaccine production are cumbersome,
      limited in scalability and often require the handling of live infectious virus.
      We describe the production of hemagglutinin from the A/Indonesia/05/05 strain of
      H5N1 influenza virus by transient expression in plants, and demonstrate the
      immunogenicity and protective efficacy of the vaccine candidate in animal models.
      Immunization of mice and ferrets with plant-derived hemagglutinin elicited serum
      hemagglutinin-inhibiting antibodies and protected the ferrets against challenge
      infection with a homologous virus. This demonstrates that plant-derived H5 HA is
      immunogenic in mice and ferrets, and can induce protective immunity against
      infection with highly pathogenic avian influenza virus. Plants could therefore be
      suitable as a platform for the rapid, large-scale production of influenza
      vaccines in the face of a pandemic.

PMID- 19100807
TI  - Comparison of efficacy of commercial one dose and two dose PCV2 vaccines using a
      mixed PRRSV-PCV2-SIV clinical infection model 2-3-months post vaccination.
AB  - The study objectives were to compare the duration of immunity of commercially
      available, one and two dose, killed porcine circovirus type 2 (PCV2) vaccines.
      Sixty, 3.5-week-old pigs were randomly divided into six treatment groups: one
      dose vaccines (FDAH-1, BIVI-1), two dose vaccines (Intervet-2, FDAH-2), and non
      vaccinated negative and positive controls. Tissue homogenate challenge was
      conducted 63 (two doses) or 84 (one dose) days post vaccination. Viremia was
      reduced by 78.5% in pigs vaccinated with one dose and by 97.1% in pigs vaccinated
      with two dose products and overall microscopic lymphoid lesions were reduced by
      78.7% and 81.8%, respectively.

PMID- 19100808
TI  - Brain glucose metabolism difference between bipolar and unipolar mood disorders
      in depressed and euthymic states.
AB  - BACKGROUND: Functional brain imaging studies have consistently demonstrated
      abnormalities in regional cerebral glucose metabolism in the prefrontal cortex in
      patients with mood disorders (MD). These studies, however, have not clarified the
      differential characteristics of glucose metabolism between depressed and euthymic
      states, or between bipolar mood disorder (BP) and unipolar mood disorder (UP).
      METHODS: We used [(18)F]fluorodeoxyglucose (FDG) positron emission tomography
      (PET) to evaluate the differences in glucose metabolism at resting state. We
      compared 30 depressed and 17 euthymic female patients with mood disorders with
      age-, IQ-, and socioeconomically matched 20 healthy controls (HCs). Then, BP and
      UP patients were separately analyzed. The PET data were objectively analyzed by
      statistical parametric mapping (SPM). RESULTS: Compared with HCs, the depressed
      MD patients showed significantly lower glucose metabolism in the bilateral
      frontal gyri, left cingulate gyrus, bilateral temporal gyri, right insula,
      bilateral inferior parietal lobules, and right occipital gyrus. In contrast, the
      euthymic MD patients demonstrated fewer areas with significant reduction. When
      the depressed BP patients were separately compared with HCs, the glucose
      metabolism was found to be significantly lower in the bilateral frontal gyri,
      right cingulate gyrus, and bilateral inferior parietal lobules. Meanwhile, the
      depressed UP patients showed a significantly lower metabolism in the bilateral
      frontal gyri, left cingulate gyrus, bilateral temporal gyri, bilateral insulae,
      bilateral inferior parietal lobules, and right occipital gyrus. CONCLUSIONS: The
      results of this study provide evidence of persistent hypometabolism in depressed
      MD patients, particularly in the frontal gyrus. Although the conclusions are
      limited in the cross-sectional study, these findings suggest that abnormalities
      in the right frontal gyrus, left temporal gyrus, and left cingulate gyrus tend to
      normalize as the depression symptoms improve, although those in the left frontal
      gyrus, right cingulate gyrus, and right temporal gyrus persist. This study also
      elucidated the cerebral hypofunction specific to each BP and UP. BP patients
      showed a decrease in glucose metabolism in the right anterior cingulate and UP
      patients did in the right temporal gyrus, right insula, and left posterior
      cingulate. This study clarified the differences between subtypes.

PMID- 19100809
TI  - Post-session injections of a protein synthesis inhibitor, cycloheximide do not
      alter saccharin self-administration.
AB  - A large body of evidence indicates that reactivation of aversive memories leads
      to protein synthesis-dependent memory reconsolidation which can be disrupted by
      cycloheximide (CHX) and other protein synthesis inhibitors. The aim of the
      present study was to investigate whether CHX would alter maintenance of well
      trained instrumental responding for 0.1% saccharin. Male Wistar rats were trained
      to lever press for saccharin. When lever pressing stabilized, experimental self
      administration sessions with CHX (3 mg/kg, s.c.) started. The animals received
      four experimental sessions, with each session separated by 5 days. The protein
      synthesis inhibitor was injected immediately after the experimental sessions 1-3.
      Repeated post-session injections of CHX did not alter saccharin self
      administration. A two-bottle choice test conducted after the last experimental
      session revealed that CHX had not induced any conditioned taste aversion to 0.1%
      saccharin. The present results suggest that well-consolidated long-term memory of
      an appetitive instrumental task does not depend on de novo protein synthesis.

PMID- 19100810
TI  - Sex differences in corticolimbic dopamine and serotonin systems in the rat and
      the effect of postnatal handling.
AB  - Stress-related psychopathology is particularly prevalent in women, although the
      neurobiological reason(s) for this are unclear. Dopamine (DA) and serotonin (5
      HT) systems however, are known to play important adaptive roles in stress and
      emotion regulation. The aims of the present study included examination of sex
      differences in stress-related behaviour and neuroendocrine function as well as
      post mortem neurochemistry, with the main hypothesis that corticolimbic DA and 5
      HT systems would show greater functional activity in males than females. Long
      Evans rats of both sexes were employed. Additional factors incorporated included
      differential postnatal experience (handled vs. nonhandled) and adult mild stress
      experience (acute vs. repeated (5) restraint). Regional neurochemistry measures
      were conducted separately for left and right hemispheres. Behaviourally, females
      showed more exploratory behaviour than males in the elevated plus maze and an
      openfield/holeboard apparatus. Females also exhibited significantly higher levels
      of adrenocorticotrophic hormone and corticosterone at all time points in response
      to restraint stress than males across treatment conditions, although both sexes
      showed similar habituation in stress-induced ACTH activation with repeated mild
      stress. Neurochemically, females had significantly higher levels of DA (in
      ventromedial prefrontal cortex (vmPFC), insular cortex and n. accumbens) and 5-HT
      (in vmPFC, amygdala, dorsal hippocampus and insula) than males. In contrast,
      males had higher levels of the DA metabolite DOPAC or DOPAC/DA ratios than
      females in all five regions and higher levels of the 5-HT metabolite 5-HIAA or 5
      HIAA/5-HT ratios in vmPFC, amygdala and insula, suggesting greater
      neurotransmitter utilization in males. Moreover, handling treatment induced a
      significant male-specific upregulation of 5-HT metabolism in all regions except
      n. accumbens. Given the adaptive role of 5-HT and DAergic neurotransmission in
      stress and emotion regulation, the intrinsic sex differences we report in the
      functional status of these systems across conditions, may be highly relevant to
      the differential vulnerability to disorders of stress and emotion regulation.

PMID- 19100811
TI  - Antioxidant activity and ultra-performance LC-electrospray ionization-quadrupole
      time-of-flight mass spectrometry for phenolics-based fingerprinting of Rose
      species: Rosa damascena, Rosa bourboniana and Rosa brunonii.
AB  - Roses are one of the most important groups of ornamental plants and their fruits
      and flowers are used in a wide variety of food, nutritional products and
      different traditional medicines. The antioxidant activity of methanolic extracts
      from fresh flowers of three rose species (Rosa damascena, Rosa bourboniana and
      Rosa brunonii) was evaluated by 1,1-diphenyl-2-picryl hydrazyl (DPPH) free
      radical method. The ability to scavenge DPPH radical was measured by the
      discoloration of the solution. The methanolic extract from R. brunonii exhibited
      maximum free-radical-scavenging activity (64.5+/-0.38%) followed by R.
      bourboniana (51.8+/-0.46%) and R. damascena (43.6+/-0.25%) at 100 microg/ml.
      Simultaneously, ultra-performance liquid chromatography coupled with electrospray
      ionization-quadrupole time-of-flight mass spectrometry (UPLC-ESI-QTOF-MS) was
      used to study phenolic composition in the methanolic extracts from the fresh
      flowers of rose species. The phenolic constituents were further investigated by
      direct infusion-ESI-QTOF-MS/MS in negative ion mode. Characteristic Electrospray
      ionization tandem mass spectrometry (ESI-MS/MS) spectra with other diagnostic
      fragment ions generated by retro Diels-Alder (RDA) fragmentation pathways were
      recorded for the flavonoids. Distinct similarities were observed in the relative
      distribution of polyphenolic compounds among the three species. The dominance of
      quercetin, kaempferol and their glycosides was observed in all the three species.

PMID- 19100812
TI  - Role of muscarinic signal transduction and CREB phosphorylation in dichlorvos
      induced memory deficits in rats: an acetylcholine independent mechanism.
AB  - The present study was designed to explore the alternative mechanism (other than
      AChE inhibition) for chronic, low-level exposure to dichlorvos, an
      organophosphate, in vivo. Dichlorvos, at a dose of 1.0 and 6.0 mg/kg body weight
      (b.wt.) for 12 weeks, showed impairment in neurobehavioral indices viz. rota rod,
      passive avoidance and water maze tests. Though high dose of dichlorvos had a
      detrimental effect on acetylcholinesterase activity, no significant inhibition
      was seen with low dose of dichlorvos. Western blot analysis and
      immunofluorescence studies showed a significant reduction in the expression of
      M(1), M(2) and M(3) muscarinic receptor subtypes in high dose group animals,
      whereas in low dose group animals only the M(2) receptor subtype was reduced
      significantly. Further, the signal transduction cascade linked to these receptor
      subtypes was affected in high dose group animals whereas in low dose group only
      adenylyl cyclase-linked signaling pathway was impaired. Finally, the
      phosphorylation of CREB, a memory enhancing transcription factor, was
      significantly reduced in both low dose and high dose group animals. Thus, the
      present study reveals the significance of M(2) muscarinic receptor linked
      adenylyl cyclase signaling pathway and phosphorylation of CREB in the development
      of neurobehavioral impairments after chronic low-level exposure to dichlorvos.

PMID- 19100813
TI  - Effects of stress on heart rate complexity--a comparison between short-term and
      chronic stress.
AB  - This study examined chronic and short-term stress effects on heart rate
      variability (HRV), comparing time, frequency and phase domain (complexity)
      measures in 50 healthy adults. The hassles frequency subscale of the combined
      hassles and uplifts scale (CHUS) was used to measure chronic stress. Short-term
      stressor reactivity was assessed with a speech task. HRV measures were determined
      via surface electrocardiogram (ECG). Because respiration rate decreased during
      the speech task (p<.001), this study assessed the influence of respiration rate
      changes on the effects of interest. A series of repeated-measures analyses of
      covariance (ANCOVA) with Bonferroni adjustment revealed that short-term stress
      decreased HR D2 (calculated via the pointwise correlation dimension PD2)
      (p<.001), but increased HR mean (p<.001), standard deviation of R-R (SDRR)
      intervals (p<.001), low (LF) (p<.001) and high frequency band power (HF)
      (p=.009). Respiratory sinus arrhythmia (RSA) and LF/HF ratio did not change under
      short-term stress. Partial correlation adjusting for respiration rate showed that
      HR D2 was associated with chronic stress (r=-.35, p=.019). Differential effects
      of chronic and short-term stress were observed on several HRV measures. HR D2
      decreased under both stress conditions reflecting lowered functionality of the
      cardiac pacemaker. The results confirm the importance of complexity metrics in
      modern stress research on HRV.

PMID- 19100814
TI  - Purification, characterization and cloning of a ricin B-like lectin from mushroom
      Clitocybe nebularis with antiproliferative activity against human leukemic T
      cells.
AB  - BACKGROUND: Lectins are a diverse group of carbohydrate-binding proteins
      exhibiting numerous biological activities and functions. METHODS: Two-step serial
      carbohydrate affinity chromatography was used to isolate a lectin from the edible
      mushroom clouded agaric (Clitocybe nebularis). It was characterized
      biochemically, its gene and cDNA cloned and the deduced amino acid sequence
      analyzed. Its activity was tested by hemagglutination assay and carbohydrate
      binding specificity determined by glycan microarray analysis. Its effect on
      proliferation of several human cell lines was determined by MTS assay. RESULTS: A
      homodimeric lectin with 15.9-kDa subunits agglutinates human group A, followed by
      B, O, and bovine erythrocytes. Hemagglutination was inhibited by glycoprotein
      asialofetuin and lactose. Glycan microarray analysis revealed that the lectin
      recognizes human blood group A determinant GalNAcalpha1-3(Fucalpha1-2)Galbeta
      containing carbohydrates, and GalNAcbeta1-4GlcNAc (N,N'-diacetyllactosediamine).
      The lectin exerts antiproliferative activity specific to human leukemic T cells.
      CONCLUSIONS: The protein belongs to the ricin B-like lectin superfamily, and has
      been designated as C. nebularis lectin (CNL). Its antiproliferative effect
      appears to be elicited by binding to carbohydrate receptors on human leukemic T
      cells. GENERAL SIGNIFICANCE: CNL is one of the few mushroom ricin B-like lectins
      that have been identified and the only one so far shown to possess
      immunomodulatory properties.

PMID- 19100815
TI  - Early postnatal exposure to methylphenidate alters stress reactivity and
      increases hippocampal ectopic granule cells in adult rats.
AB  - To mimic clinical treatment with methylphenidate (MPH; Ritalin) for attention
      deficit/hyperactivity disorder (ADHD), rat pups were injected with MPH (5 mg/kg,
      i.p.) or placebo twice daily during their nocturnal active phase from postnatal
      day (PND) 7-35. Thirty-nine days after the last MPH administration (PND 76), four
      litters of rats experienced stressful conditions during the 2003 New York City
      blackout. MPH-treated rats that endured the blackout lost more weight and
      regained it at a slower pace than controls (p<0.05; N=7-11 per group).
      Furthermore, MPH-treated rats had elevated systolic arterial blood pressure (from
      115.6+/-1.2 to 126+/-1.8 mmHg; p<0.05), assessed on PND 130 by tail cuff
      plethysmography. Immunocytochemical studies of transmitter systems in the brain
      demonstrated rearrangements of catecholamine and neuropeptide Y fibers in select
      brain regions at PND 135, which did not differ between blackout and control
      groups. However, MPH-treated rats that endured the blackout had more ectopic
      granule cells in the hilus of the dorsal hippocampal dentate gyrus compared to
      controls at PND 135 (p<0.05; N=6 per group). These findings indicate that early
      postnatal exposure to high therapeutic doses of MPH can have long lasting effects
      on the plasticity of select brain regions and can induce changes in the
      reactivity to stress that persist into adulthood.

PMID- 19100816
TI  - Molecular characterization of Desmodium species--an important ingredient of
      'Dashmoola' by RAPD analysis.
AB  - Identification of medicinal plants by their molecular signature is a fast growing
      tool. The identification of Desmodium gangeticum (L.) DC. (Shalparni, a
      constituent of Ayurvedic formulation "Dashmoolarishtha") was carried out using
      genomic approach. Authentic samples of D. gangeticum(L.) DC., D. velutinum
      (Willd.) DC. and D. triflorum (L.) DC. were analyzed and compared to commercial
      samples of various origin. Within twenty primers used, eleven gave 223 RAPD
      fragments. RAPD profiles of three species showed very low similarity index (0.21
      0.39), whereas market samples showed high similarity of 0.82-0.89 with
      authenticated D. gangeticum.

PMID- 19100817
TI  - C-glycosyl flavones from Peperomia blanda.
AB  - The methanol extract from aerial parts of the Peperomia blanda (Piperaceae)
      yielded two C-glycosyl-flavones. Their structures were elucidated on the basis of
      extensive spectroscopic analysis, including 1D and 2D NMR, chemical
      transformation and comparison with the related known compounds. The structure of
      the new flavonoids were established as 4'-methoxy-vitexin 7-O-beta-D
      xylopyranoside (1) (7-O-beta-D-xylopyranosyl-8-C-beta-D-glucopyranosyl-4'-methoxy
      apigenin) and vicenin-2 (2). The antioxidant activity of both compounds was
      investigated using the DPPH assay. Both compounds showed only modest activity,
      with IC50 values of 357.2 microM for 1, and 90.5 microM for 2.

PMID- 19100818
TI  - The complete mitochondrial genome of the large yellow croaker, Larimichthys
      crocea (Perciformes, Sciaenidae): unusual features of its control region and the
      phylogenetic position of the Sciaenidae.
AB  - To understand the systematic status of Larimichthys crocea in the Percoidei, we
      determined the complete mitochondrial (mt) genome sequence using 454 sequencing
      by-synthesis technology. The complete mt genome is 16,466 bp in length including
      the typical structure of 22 tRNAs, 2 rRNAs, 13 protein-coding genes and the
      noncoding control region (CR). Further sequencing for the complete CR was
      performed using the primers Cyt b-F and 12S-R on six L. crocea individuals and
      two L. polyactis individuals. Interestingly, all seven CR sequences from L.
      crocea were identical while the three sequences from L. polyactis were distinct
      (including one from GenBank). Although the conserved blocks such as TAS and CSB
      1, -2, and -3 are readily identifiable in the control regions of the two species,
      the typical central conserved blocks CSB-D, -E, and -F could not be detected,
      while they are found in Cynoscion acoupa of Sciaenidae and other Percoidei
      species. Phylogenetic analysis shows that L. crocea is a relatively recently
      emerged species in Sciaenidae and this family is closely related to family
      Pomacanthidae within the Percoidei. L. crocea, as the first species of Sciaenidae
      with complete mitochondrial genome available, will provide important information
      on the molecular evolution of the group. Moreover, the genus-specific pair of
      primers designed in this study for amplifying the complete mt control region will
      be very useful in studies on the population genetics and conservation biology of
      Larimichthys.

PMID- 19100819
TI  - Echinococcus granulosus tropomyosin isoforms: from gene structure to expression
      analysis.
AB  - Tropomyosins (Trps) constitute a family of actin filament-binding proteins found
      in all eukaryotic cells. In muscle cells, they play a central role in contraction
      by regulating calcium-sensitive interaction of actin and myosin. In non-muscle
      cells, tropomyosins regulate actin filament organization and dynamics. Trps genes
      exhibit extensive cell type-specific isoform diversity generated by alternative
      splicing. Here, we report the characterization of tropomyosin gene transcribed
      sequences from the parasitic platyhelminth Echinococcus granulosus. Using RT-PCR
      approach we isolated three isoforms (egtrpA, egtrpB and egtrpC), which display
      significant homologies to know tropomyosins of different phylogenetic origin. The
      corresponding gene, egtrp (5656 bp), contains eight introns and nine exons.
      Southern blot hybridization studies showed that egtrp is present as single copy
      locus in E. granulosus. We demonstrated that egtrp expresses three different
      transcripts which differ in alternatively spliced exon 4 and intron VI.
      Interestingly, intron VI suffers intron retention and contains an internal stop
      codon in frame. Three major bands are also detected by Western blot analysis
      using a specific anti-rEgTrp antiserum. Immune-localization and in situ
      hybridization studies showed that egtrp transcription and translation is mostly
      localized at the protoscoleces suckers. This is the first report of alternative
      splicing in this parasite.

PMID- 19100820
TI  - Prenatal administration of indomethacin modulates Th2 cytokines in juvenile rats.
AB  - Indomethacin (IND) suppresses the T-dependent antibody response (TDAR) in
      juvenile males when it is administered to pregnant rats during late gestation. In
      this study, the effect of IND on cytokine production in juvenile rats was
      examined to investigate the mechanism behind the suppression of antibody
      production. IND was orally administered to pregnant SD rats on days 18-21 of
      gestation. After parturition, the spleen cells isolated from 3-week-old pups were
      incubated with concanavalin A (Con A) or lipopolysaccharide (LPS). The level of
      cytokines in the culture supernatant was measured. IL-10 decreased significantly
      in the males, and IL-6 and TNF-alpha tended to decrease in both sexes. In order
      to examine the effect of IND on cytokine production in juvenile rats in vitro,
      spleen cells isolated from untreated 3-week-old rats were exposed to IND and a
      mitogen (Con A or LPS) simultaneously, and then the levels of cytokines were
      measured. IL-4 decreased in the males, and IL-6 tended to decrease in both sexes.
      These results indicated that treating dams with IND during late gestation causes
      a change in the release of Th2 cytokine, and suggested that this change involves
      the suppression of antibody production.

PMID- 19100821
TI  - Transdermal drug pharmacokinetics in man: Interindividual variability and partial
      prediction.
AB  - A database of human dermatopharmacokinetic parameters of 12 transdermal patches
      is established. The effect of system design, application site, and metabolism on
      pharmacokinetic data is discussed, and interindividual variability of data and
      its possible sources evaluated. Using multiple regression analysis, two equations
      based on drugs physicochemical characteristics are suggested for partial
      prediction of peak plasma concentration (C(max)) after patch application. Patch
      application presumably decreases variance as rub-off, wash and exfoliation steps
      are diminished. The results showed that interindividual variation, in terms of
      coefficient of variation (CV) of C(max), is inversely correlated with drugs
      molecular weight and lipophilicity in the range of 200<MW<400 and
      1.6<logK(oct)<4.3. Multiple regression analysis of C(max) against
      physichochemical parameters demonstrated the prominent contribution of hydrogen
      bonding acceptability of the molecules on their maximal plasma concentration
      after patch administration. The findings suggest that the serum concentration
      profile for transdermal therapeutic systems (TTS) is a net result of the system
      performance, drug absorption and elimination. Thus, the variability in serum
      concentration is a function of variability of each process involved. This should
      be noted in explanation of effect of molecular features of drugs on their plasma
      concentration profile.

PMID- 19100822
TI  - Mechanisms of drug release in citrate buffered HPMC matrices.
AB  - Few studies report the effects of alkalizing buffers in HPMC matrices. These
      agents are incorporated to provide micro-environmental buffering, protection of
      acid-labile ingredients, or pH-independent release of weak acid drugs. In this
      study, the influence of sodium citrate on the release kinetics, gel layer
      formation, internal gel pH and drug release mechanism was investigated in HPMC
      2910 and 2208 (Methocel E4M and K4M) matrices containing 10% felbinac 39% HPMC,
      dextrose and sodium citrate. Matrix dissolution at pH 1.2 and pH 7.5 resulted in
      complex release profiles. HPMC 2910 matrices exhibited biphasic release, with
      citrate increasing the immediate release phase (<60min) and reducing the extended
      release. HPMC 2208 matrices were accelerated, but without the loss of extended
      release characteristics. Studies of early gel layer formation suggested gel
      barrier disruption and enhanced liquid penetration. pH modification of the gel
      layer was transitory (<2h) and corresponded temporally with the immediate release
      phase. Results suggest that in HPMC 2910 matrices, high initial citrate
      concentrations within the gel layer suppress particle swelling, interfere with
      diffusion barrier integrity, but are lost rapidly whereupon drug solubility
      reduces and the diffusion barrier recovers. These Hofmeister or osmotic-mediated
      effects are better resisted by the less methoxylated HPMC 2208.

PMID- 19100823
TI  - Inhibition of breast cancer metastasis by dual liposomes to disturb complex
      formation.
AB  - The interaction between tumour cells and blood components, mainly platelets,
      plays an important role in metastasis. In this study, the anti-metastatic effect
      of vesicles containing the cytotoxic drug perifosine (OPP) and the haemostatic
      inhibitor dipyridamole (DIP) was tested. These dual liposomes (DIP/OPP-L)
      encapsulating up to 400microg DIP/ml and 6mM OPP were prepared by extrusion
      technique. In vitro, DIP/OPP-L significantly inhibited the aggregation of
      platelets and reduced their adhesion to immobilized MT3 cells by up to 60% and
      24.7%, respectively. Complex formation between platelets and tumour cells in
      vitro was completely prevented by DIP/OPP-vesicles. These combinatory liposomes
      also inhibited the metastatic capacity of circulating tumour cells by reducing
      the complex formation with platelets. Formation of lung and extrapulmonary
      metastases after intravenous administration of MT3 breast cancer cells was
      significantly reduced when mice were treated with a single intravenous dose of
      DIP/OPP-L containing 100nmol lipid 6h before tumour cell inoculation.

PMID- 19100824
TI  - Inhibiting efflux with novel non-ionic surfactants: Rational design based on
      vitamin E TPGS.
AB  - Tocopheryl Polyethylene Glycol Succinate 1000 (TPGS 1000) can inhibit P
      glycoprotein (P-gp); TPGS 1000 was not originally designed to inhibit an efflux
      pump. Recent work from our laboratories demonstrated that TPGS activity has a
      rational PEG chain length dependency. In other recent work, inhibition mechanism
      was investigated and appears to be specific to the ATPase providing P-gp energy.
      Based on these observations, we commenced rational surface-active design. The
      current work summarizes new materials tested in a validated Caco-2 cell monolayer
      model; rhodamine 123 (10microM) was used as the P-gp substrate. These results
      demonstrate that one may logically construct non-ionic surfactants with enhanced
      propensity to inhibit in vitro efflux. One new surfactant based inhibitor,
      Tocopheryl Polypropylene Glycol Succinate 1000 (TPPG 1000), approached
      cyclosporine (CsA) in its in vitro efflux inhibitory potency. Subsequently, TPPG
      1000 was tested for its ability to enhance the bioavailability of raloxifene - an
      established P-gp substrate -in fasted male rats. Animals dosed with raloxifene
      and TPPG 1000 experienced an increase in raloxifene oral bioavailability versus a
      control group which received no inhibitor. These preliminary results demonstrate
      that one may prepare TPGS analogs that possess enhanced inhibitory potency in
      vitro and in vivo.

PMID- 19100825
TI  - A novel zein-based dry coating tablet design for zero-order release.
AB  - The purpose of this study was to design zero-order release of dry-coated tablets
      using pure zein powder, zein granule and zein blend containing two common
      pharmaceutical excipients such as microcrystalline cellulose (MCC) or starch in
      different proportions as coating material. The 5-fluorouracil (5-FU) was used as
      a model drug. The physical characterization and drug release behaviors of dry
      coated tablets were investigated. The surface structure of the tablets was
      examined by a scanning electron microscopy. The correlation coefficient (R) was
      used as indicator of the best fitting of the zero-order model for drug release.
      It was found that zein formed a gelatinous layer fast and its network prevented
      disintegration of the tablet during dissolution process. Zein-based dry coating
      tablets had good physical properties such as compactibility and friability. All
      formulations fit the zero-order model well. The mechanism for zero-order release
      of these dry-coated tablets was solvent penetration into the dosage form and
      dissolving the drug, the dissolving core formed an apex in the center of the
      tablets and the drug diffused out. The apex of zein-coated tablets worked as
      orifice of an osmotic system and released the drug in zero-order profile.

PMID- 19100826
TI  - Lignocellulosic residues: biodegradation and bioconversion by fungi.
AB  - The ability of fungi to degrade lignocellulosic materials is due to their highly
      efficient enzymatic system. Fungi have two types of extracellular enzymatic
      systems; the hydrolytic system, which produces hydrolases that are responsible
      for polysaccharide degradation and a unique oxidative and extracellular
      ligninolytic system, which degrades lignin and opens phenyl rings.
      Lignocellulosic residues from wood, grass, agricultural, forestry wastes and
      municipal solid wastes are particularly abundant in nature and have a potential
      for bioconversion. Accumulation of lignocellulosic materials in large quantities
      in places where agricultural residues present a disposal problem results not only
      in deterioration of the environment but also in loss of potentially valuable
      material that can be used in paper manufacture, biomass fuel production,
      composting, human and animal feed among others. Several novel markets for
      lignocellulosic residues have been identified recently. The use of fungi in low
      cost bioremediation projects might be attractive given their lignocellulose
      hydrolysis enzyme machinery.

PMID- 19100827
TI  - Klebsiella pneumoniae MrkD adhesin-mediated immunity to respiratory infection and
      mapping the antigenic epitope by phage display library.
AB  - In this study, the K. pneumoniae MrkD adhesin was identified an immunodominant
      antigen which correlated with protection against infection by K. pneumoniae. The
      mouse monoclonal antibodies (mAbs) against MrkD adhesin were produced by the
      hybridoma technique using recombinant MrkD-GST as the immunogen and were
      immunoscreened against phage-displayed random dodecapeptide library (Ph.D.-12).
      After three rounds of biopanning, 36 phage clones were randomly selected and
      their specificity to mAb was verified by sandwich and competitive inhibition
      ELISA. Sixteen phage clones were sequenced and their amino acids were deduced.
      One mimotope (QKTLAKSTYMSA) showed good match with MrkD adhesion at 148-159 aa
      and the serum of mice induced by the phage clone clearly recognized MrkD
      adhesion.

PMID- 19100828
TI  - Increased aquaglyceroporin 9 expression disrupts arsenic resistance in human lung
      cancer cells.
AB  - Resistance to chemotherapy is one of the major problems in treatment responses of
      lung cancer. This study explored the mechanism underlying the arsenic resistance
      of lung cancer. Four lung cancer cells with different proliferation activity were
      characterized for cytotoxicity, arsenic influx/efflux, and arsenic effects on
      intracellular glutathione and 8-hydroxy-2'-deoxyguanosine (8-OHdG) production.
      Our data revealed that relative proliferation potency of these cells was
      H1299>A549>CL3>H1355. Moreover, A549, H1299, and H1355 were markedly resistant to
      As(2)O(3) with IC50 approximately 100 microM, whereas CL3 was sensitive to
      As(2)O(3) with IC50 approximately 11.8 microM. After treatment with the
      respective As(2)O(3) at IC50, arsenic influx/efflux activity in CL3 was
      comparable to those in the other three arsenic-resistant cells. However,
      differences in glutathione levels and 8-OHdG production were also detected either
      before or after arsenic treatment, indicating that a certain degree of variation
      in anti-oxidative systems and/or 8-OHdG repair activity existed in these cell
      lines. By transfection of an aquaglyceroporin 9 (AQP9) gene, we showed that
      increased AQP9 expression significantly enhanced arsenic uptake and disrupted
      arsenic resistance of A549. The present study strongly suggests that membrane
      transporters responsible for arsenic uptake, such as AQP9, may play a critical
      role in development of arsenic resistance in human lung cancer cells.

PMID- 19100829
TI  - Supression of hemin-mediated oxidation of low-density lipoprotein and subsequent
      endothelial reactions by hydrogen sulfide (H(2)S).
AB  - Heme-mediated oxidative modification of low-density lipoprotein (LDL) plays a
      crucial role in early atherogenesis. It has been shown that hydrogen sulfide
      (H(2)S) produced by vascular smooth muscle cells is present in plasma at a
      concentration of about 50 micromol/L. H(2)S is a strong reductant which can react
      with reactive oxygen species like superoxide anion and hydrogen peroxide. The
      current study investigated the effect of H(2)S on hemin-mediated oxidation of LDL
      and oxidized LDL (oxLDL)-induced endothelial reactions. H(2)S dose dependently
      delayed the accumulation of lipid peroxidation products-conjugated dienes, lipid
      hydroperoxides (LOOH), and thiobarbituric acid reactive substances-during hemin
      mediated oxidation. Moreover, H(2)S decreased the LOOH content of both oxidized
      LDL and lipid extracts derived from soft atherosclerotic plaque, which was
      accompanied by reduced cytotoxicity. OxLDL-mediated induction of the oxidative
      stress responsive gene, heme oxygenase-1, was also abolished by H(2)S. Finally we
      have shown that H(2)S can directly protect endothelium against hydrogen peroxide
      and oxLDL-mediated endothelial cytotoxicity. These results demonstrate novel
      functions of H(2)S in preventing hemin-mediated oxidative modification of LDL,
      and consequent deleterious effects, suggesting a possible antiatherogenic action
      of H(2)S.

PMID- 19100830
TI  - Potent inhibition of superoxide anion production in activated human neutrophils
      by isopedicin, a bioactive component of the Chinese medicinal herb Fissistigma
      oldhamii.
AB  - Fissistigma oldhamii is widely used in traditional Chinese medicine to treat
      rheumatoid arthritis. Activation of neutrophils is a key feature of inflammatory
      diseases. Herein, the anti-inflammatory functions of isopedicin, a flavanone
      derived from F. oldhamii, and its underlying mechanisms were investigated in
      human neutrophils. Isopedicin potently and concentration-dependently inhibited
      superoxide anion (O(2)(*)(-)) production in formyl-L-methionyl-L-leucyl-L
      phenylalanine (FMLP)-activated human neutrophils with an IC(50) value of 0.34+/
      0.03 microM. Furthermore, isopedicin displayed no superoxide-scavenging ability,
      and it failed to alter subcellular NADPH oxidase activity. The inhibitory effect
      of isopedicin on O(2)(*)(-) production was reversed by protein kinase A (PKA)
      inhibitors. Moreover, isopedicin increased cAMP formation and PKA activity in
      FMLP-activated human neutrophils, which occurred through the inhibition of
      phosphodiesterase (PDE) activity but not an increase in adenylate cyclase
      function. In addition, isopedicin reduced FMLP-induced phosphorylation of
      extracellular regulated kinase and c-Jun N-terminal kinase, which was reversed by
      the PKA inhibitor. In contrast, isopedicin failed to alter FMLP-induced
      phosphorylation of p38 mitogen-activated protein kinase and calcium mobilization.
      In summary, these results demonstrate that inhibition of O(2)(*)(-) production in
      human neutrophils by isopedicin is associated with an elevation of cellular cAMP
      and activation of PKA through its inhibition of cAMP-specific PDE.

PMID- 19100831
TI  - The molecular mechanism and cellular functions of mitochondrial division.
AB  - Mitochondria are highly dynamic organelles that continuously divide and fuse.
      These dynamic processes regulate the size, shape, and distribution of the
      mitochondrial network. In addition, mitochondrial division and fusion play
      critical roles in cell physiology. This review will focus on the dynamic process
      of mitochondrial division, which is highly conserved from yeast to humans. We
      will discuss what is known about how the essential components of the division
      machinery function to mediate mitochondrial division and then focus on proteins
      that have been implicated in division but whose functions remain unclear. We will
      then briefly discuss the cellular functions of mitochondrial division and the
      problems that arise when division is disrupted.

PMID- 19100833
TI  - Molecular basis of female-specific odorant responses in Bombyx mori.
AB  - Males and females of many moth species exhibit important differences in sexual
      behaviours. Much research in this field has focused on the male-specific
      behaviour, electrophysiology and molecular biology of sex pheromone reception.
      Female-specific behaviours have been less well studied although, like male
      specific behaviours, they could provide opportunities for intervention and
      management of lepidopteran pests. Previously, we identified genes encoding
      putative odorant receptors (ORs) from the genome of the silkworm, Bombyx mori,
      some of which have higher levels of steady-state transcript in the antennae of
      adult females compared with males. We have identified the full-length cDNA
      sequences of some of these ORs and described a novel OR that is part of a female
      biased clade. Using expression in Sf9 cells and a calcium-imaging assay, we
      tested a range of compounds for their ability to activate the most highly female
      biased ORs, BmOR19, BmOR30, BmOR45 and BmOR47. BmOR19 responds to linalool, while
      BmOR45 and BmOR47 respond to benzoic acid > 2-phenylethanol > benzaldehyde. No
      activating ligands were found for BmOR30. RNA in situ hybridisation experiments
      reveal that BmOR19 is expressed in female olfactory sensory neurons that are co
      located in the same sensilla as a second ORN expressing BmOR45 and/or BmOR47.
      Taken together the activity and expression of these receptors is likely
      explanatory of the observed electrophysiology of long sensilla trichoidea of
      female B. mori, previously shown to each contain one terpene (BmOR19) and one
      benzoic acid (BmOR45, BmOR47) sensory neuron. Plant volatiles such as linalool,
      benzoic acid, 2-phenylethanol and benzaldehyde are oviposition cues for females
      of some moths. These compounds have also been found in male-produced pheromone
      blends extracted from the hair pencils of many noctuid species. Hair pencil
      structures have not previously been reported for B. mori, but we have found hair
      pencil-like structures in adult male B. mori that are absent in female moths. It
      is proposed that BmOR19, BmOR45 and BmOR47 account for some of the female
      specific odorant responses in B. mori, such as oviposition and/or detection of an
      as yet unidentified male-produced sex pheromone.

PMID- 19100832
TI  - Requirement of Wnt/beta-catenin signaling in pronephric kidney development.
AB  - The pronephric kidney controls water and electrolyte balance during early fish
      and amphibian embryogenesis. Many Wnt signaling components have been implicated
      in kidney development. Specifically, in Xenopus pronephric development as well as
      the murine metanephroi, the secreted glycoprotein Wnt-4 has been shown to be
      essential for renal tubule formation. Despite the importance of Wnt signals in
      kidney organogenesis, little is known of the definitive downstream signaling
      pathway(s) that mediate their effects. Here we report that inhibition of Wnt/beta
      catenin signaling within the pronephric field of Xenopus results in significant
      losses to kidney epithelial tubulogenesis with little or no effect on adjoining
      axis or somite development. We find that the requirement for Wnt/beta-catenin
      signaling extends throughout the pronephric primordium and is essential for the
      development of proximal and distal tubules of the pronephros as well as for the
      development of the duct and glomus. Although less pronounced than effects upon
      later pronephric tubule differentiation, inhibition of the Wnt/beta-catenin
      pathway decreased expression of early pronephric mesenchymal markers indicating
      it is also needed in early pronephric patterning. We find that upstream
      inhibition of Wnt/beta-catenin signals in zebrafish likewise reduces pronephric
      epithelial tubulogenesis. We also find that exogenous activation of Wnt/beta
      catenin signaling within the Xenopus pronephric field results in significant
      tubulogenic losses. Together, we propose Wnt/beta-catenin signaling is required
      for pronephric tubule, duct and glomus formation in Xenopus laevis, and this
      requirement is conserved in zebrafish pronephric tubule formation.

PMID- 19100835
TI  - Androgens inhibit androgen receptor promoter activation in motor neurons.
AB  - The androgen receptor (AR), a ligand-activated transcription factor, has been
      found mutated in several human diseases. While some mutations reduce, others
      potentiate AR functions generating different endocrine dysfunctions. A peculiar
      AR mutation, the CAG-repeat expansion encoding the AR-polyglutamine (polyQ)
      tract, generates a neurotoxic gain-of-function(s) in this mutant AR (ARpolyQ).
      This leads to the motor neuronal disease Spinal and Bulbar Muscular Atrophy
      (SBMA), in which the transcriptional AR down-regulation might have beneficial
      impacts. We thus analysed the AR-promoter/5'-UTR activation and androgenic
      regulation, demonstrating that its constitutive activity is considerably high in
      motor neurons (NSC34). Testosterone, dihydrotestosterone (DHT), but not
      estradiol, inhibited AR promoter activation. Thus AR establishes a negative
      control on its own functions, in opposition to that described on classical
      androgen-responsive elements (ARE) of the AR gene. The AR/DNA interaction is
      required for this action, since DHT does not inhibit AR expression in presence of
      an AR (AR_DeltaPhe581) lacking DNA binding activity. The minimal inhibitory
      region spans from -740/+570 bp, where "in silico" analysis showed a putative AR
      binding site; deletion studies excluded that this ARE may be involved in this
      inhibition. A similar effect of DHT has also been observed in AR negative
      prostate cancer DU145 cell line transfected with the AR. Moreover, androgens down
      regulate the expression of the endogenous AR gene in an AR positive prostate
      cancer LNCaP cell line. Interestingly, in immortalized motor neurons, ARpolyQ was
      much less effective than wtAR on the positive androgenic control on classical
      AREs, while ARpolyQ and wtAR had similar inhibitory properties on the AR
      promoter/5'-UTR activation. This strongly suggests that, in motor neurons, the
      two types of AR gene androgenic regulation involve different mechanisms. Thus, by
      acting on the AR promoter it would be possible to reduce AR levels in motor
      neurons, providing novel approaches to treat SBMA.

PMID- 19100834
TI  - Unaltered levels of transplant arteriosclerosis in the absence of the B cell
      homing chemokine receptor CXCR5.
AB  - Chemokine receptors and their ligands are crucial for lymphocyte trafficking
      under both homeostatic and inflammatory conditions. The chemokine receptor CXCR5
      controls B cell migration and the organization of B cell follicles. The aim of
      this study was to investigate the impact of CXCR5 on the development of
      transplant arteriosclerosis. Fully MHC mismatched BALB/c (H2(d)) donor aortas
      were transplanted into C57BL/6-CXCR5(-/-) (H2(b)), C57BL/6-CXCR5(+/-) (H2(b)) or
      C57BL/6-CXCR5(+/+) (H2(b)) recipients. Grafts were analysed by morphometry and
      immunofluorescence and intra-graft cytokine mRNA production was analysed by RT
      PCR. Transplant arteriosclerosis was evident in CXCR5+/+ and CXCR5+/- mice and
      only mildly reduced in CXCR5-/- recipients indicating that absence of CXCR5 had
      no substantial effect on the development of transplant arteriosclerosis. Analysis
      of the cellular infiltrate of aortic grafts implanted in CXCR5-/- recipients
      revealed no differences in the number of T-cells, macrophages and B cells as
      compared to controls. Intra-graft cytokine production showed no significant
      changes in Th1 (IL-12) and Th2 (IL-4) cytokines as well as in TGF-beta and iNOS
      production. These data suggest that lack of CXCR5 expression by recipient T- and
      B-cells has little effect on the development of transplant arteriosclerosis.

PMID- 19100836
TI  - Characterization and comparative analyses of zebrafish intelectins: highly
      conserved sequences, diversified structures and functions.
AB  - Intelectin family, also called the X-lectin family, is a newly discovered gene
      family involved in development and innate immunity. However, no research was
      carried out for this gene family in the model organism zebrafish. Here we present
      the first characterization of seven zebrafish intelectins (zINTLs) and the first
      systematic comparative analysis of intelectins from various species in order to
      provide some clues to the function and evolution of this gene family. We examined
      the expression patterns of zINTLs in various development stages, normal adults,
      and Aeromonas salmonicida infected adults. Results showed that zINTL1-3 were
      highly expressed in one or several adult tissues. zINTL4-7, however, were
      expressed at quite low levels both in adults and various development stages, and
      some of them showed relaxation of functional constrains as revealed by K(a)/K(s)
      calculation. Of the seven zINTLs, zINTL3 was expressed predominantly in the liver
      and highly up-regulated upon infection, suggesting its important roles in
      immunity. Based on the characterization of zebrafish intelectins, we then
      conducted a systematic survey of intelectin members in various species and made
      comparative analyses. We found out that intelectin family may be a deuterostome
      specific gene family; and their expression patterns, quaternary structures and
      glycosylations vary considerably among various species, though their sequences
      are highly conserved. Moreover, these varied features have evolved multiple times
      independently in different species, resulting in species-specific protein
      structures and expression patterns.

PMID- 19100837
TI  - Ontogeny of lymphoid organs and development of IgM-bearing cells in Atlantic
      halibut (Hippoglossus hippoglossus L.).
AB  - In teleost fish, the head kidney, thymus, and spleen are generally regarded as
      important immune organs. In this study, the ontogeny of these organs was studied
      in Atlantic halibut (Hippoglossus hippoglossus), larvae at various stages of
      development. We observed that the kidney was present at hatching, the thymus at
      33days post hatch (dph), while the spleen was the last organ to be detected at
      49dph. All three lymphoid organs were morphologically well developed during late
      metamorphic stages. Real time RT-PCR analysis showed that IgM mRNA expression
      could be observed at 66dph and later, which correlates well with in situ
      hybridisation data showing that a few IgM positive cells could be detected in the
      anterior kidney and spleen from 66dph. Our data also showed that the highest
      levels of IgM mRNA could be detected in halibut spleen. Immunostaining using a
      monoclonal antibody against halibut IgM detected IgM positive cells at 94dph in
      both the head kidney and the spleen, which is much later than the IgM mRNA.
      Numerous cells expressing both IgM mRNA and protein could be detected in the
      spleen and anterior kidney and also to some extent in thymus specimens from adult
      halibut.

PMID- 19100838
TI  - Molecular characterisation and expression analysis of interferon gamma in
      Atlantic cod (Gadus morhua).
AB  - Interferon gamma (IFN-gamma) has important roles in both innate and adaptive
      immune responses. In this study, the cDNA and genomic sequences of Atlantic cod
      IFN-gamma were cloned and found to encode a putative protein containing 194 amino
      acids with a 24 amino acid signal peptide sequence. The gene is composed of four
      exons and three introns similar to IFN-gamma genes of other vertebrates. The cod
      IFN-gamma showed only 14-29% amino acid identity with other fish IFN-gamma and 9
      17% identity with IFN-gamma from higher vertebrates. However, cod IFN-gamma
      possesses the typical IFN-gamma motifs in the C-terminal end of the protein and
      displays an alpha-helix structure similar to mammalian IFN-gamma. The promoter
      region contains a putative ISRE element indicating up-regulation by type I IFNs
      and dsRNA. Real time RT-PCR analysis confirmed that IFN-gamma gene expression was
      up-regulated in organs of cod injected with the dsRNA polyinosinic:polycytidylic
      acid (poly I:C), which is a strong inducer of type I IFNs. Injection of cod with
      formalin-killed Vibrio anguillarum also increased IFN-gamma expression in head
      kidney, but to a much lesser extent than poly I:C. The gene expression results
      thus indicate a role for IFN-gamma in innate immune response against both virus
      and bacteria in Atlantic cod.

PMID- 19100840
TI  - Imagined locomotion in the blind: an fMRI study.
AB  - Functional magnetic resonance imaging (fMRI) in sighted individuals previously
      showed parahippocampal and fusiform activations during locomotor imagery, which
      were interpreted to reflect visuospatial navigation. Concurrent deactivations of
      multisensory vestibular and somatosensory cortical areas may reflect suppression
      of vestibular and somatosensory input, in order to prevent adverse interactions
      of sensory signals with the optimized automated locomotion pattern. In this fMRI
      study we compared blood oxygen level dependent (BOLD) activations and
      deactivations during the kinesthetic imagery of standing, walking, and running in
      seven congenitally totally blind subjects, seven sighted age-matched controls,
      and five subjects with age at onset of complete blindness > or =9 y or minimal
      residual vision. Imagined lying served as the rest condition. As opposed to their
      sighted controls, congenitally totally blind individuals activated multisensory
      vestibular areas in the posterior insula and superior temporal gyrus during
      imagined locomotion. Further, congenitally blind individuals did not show
      activations in parahippocampal and fusiform regions during locomotor tasks. In
      the intergroup comparisons, congenitally blind subjects exhibited higher BOLD
      activity levels than sighted subjects in multisensory vestibular (posterior
      insula and adjacent temporal sites), somatosensory (postcentral gyrus), and
      primary motor cortical areas, while sighted subjects showed higher activity
      levels in the parahippocampal and fusiform gyri. These findings indicate that
      blind subjects rely more on vestibular and somatosensory feedback for locomotion
      control than sighted subjects. This is accompanied by enhanced voluntary motor
      control and enhanced motor-kinesthetic processing. Thus, we provide neuroimaging
      evidence of distinct sensorimotor strategies in the blind for locomotor control.

PMID- 19100841
TI  - ERP indices of persisting and current inhibitory control: a study of saccadic
      task switching.
AB  - Previous studies have found that inhibition of a biologically dominant prepotent
      response tendency is required during the execution of a less familiar, non
      prepotent response. However, the lasting impact of this inhibition and the
      cognitive mechanisms to flexibly switch between prepotent and non-prepotent
      responses are poorly understood. We examined the neurophysiological (ERP)
      correlates of switching between prosaccade and antisaccade responses in 22
      healthy volunteers. The behavioural data showed significant switch costs in terms
      of response latency for the prosaccade task only. These costs occurred
      exclusively in trials when preparation for the switch was limited to 300 ms,
      suggesting that inhibition of the prepotent prosaccade task either passively
      dissipated or was actively overcome during the longer 1000 ms preparation
      interval. In the neurophysiological data, a late frontal negativity (LFN) was
      visible during preparation for a switch to the prosaccade task that was absent
      when switching to the antisaccade task, which may reflect the overcoming of
      persisting inhibition. During task implementation both saccade types were
      associated with a late parietal positivity (LPP) for switch relative to
      repetition trials, possibly indicating attentional reorienting to the switched-to
      task, and visible only with short preparation intervals. When the prosaccade and
      antisaccade task were contrasted directly during task implementation, the
      antisaccade task exhibited increased stimulus-locked N2 and decreased P3
      amplitudes indicative of active inhibition. The present findings indicate that
      neurophysiological markers of persisting and current inhibition can be revealed
      using a prosaccade/antisaccade-switching task.

PMID- 19100839
TI  - Decreased white matter integrity in late-myelinating fiber pathways in
      Alzheimer's disease supports retrogenesis.
AB  - The retrogenesis model of Alzheimer's disease (AD) posits that white matter (WM)
      degeneration follows a pattern that is the reverse of myelogenesis. Using
      diffusion tensor imaging (DTI) to test this model, we predicted greater loss of
      microstructural integrity in late-myelinating WM fiber pathways in AD patients
      than in healthy older adults, whereas differences in early-myelinating WM fiber
      pathways were not expected. We compared 16 AD patients and 14 demographically
      matched healthy older adults with a whole-brain approach via tract-based spatial
      statistics (TBSS), and a region of interest (ROI) approach targeting early
      myelinating (posterior limb of internal capsule, cerebral peduncles) and late
      myelinating (inferior longitudinal fasciculus [ILF], superior longitudinal
      fasciculus [SLF]) fiber pathways. Permutation-based voxelwise analysis supported
      the retrogenesis model. There was significantly lower fractional anisotropy (FA)
      in AD patients compared to healthy older adults in late-myelinating but not early
      myelinating pathways. These group differences appeared to be driven by loss of
      myelin integrity based on our finding of greater radial diffusion in AD than in
      healthy elderly. ROI analyses were generally in agreement with whole-brain
      findings, with significantly lower FA and increased radial diffusion in the ILF
      in the AD group. Consistent with the retrogenesis model, AD patients showed
      demonstrable changes in late-myelinating WM fiber pathways. Given greater change
      in the ILF than the SLF, wallerian degeneration secondary to cortical atrophy may
      also be a contributing mechanism. Knowledge of the pattern of WM microstructural
      changes in AD and its underlying mechanisms may contribute to earlier detection
      and intervention in at-risk groups.

PMID- 19100842
TI  - Simultaneous, live imaging of cortical spreading depression and associated
      cerebral blood flow changes, by combining voltage-sensitive dye and laser speckle
      contrast methods.
AB  - Cortical spreading depression (i.e. waves of cellular depolarization, CSD) causes
      the aura symptoms in classical migraine, and may contribute to delayed cellular
      damage after an ischemic or traumatic insult to the brain. In the latter cases,
      secondary neuronal injury may be worsened by some of the cerebral blood flow
      (CBF) changes that are associated with CSD. Here, we describe a new method for
      the simultaneous, live imaging of local cellular depolarization and CBF changes
      (i.e. two variables with well-defined and important biological significance),
      through a closed cranial window prepared in anesthetized rats. This novel
      experimental strategy was validated by imaging the changes associated with CSD
      elicited by application of high K(+) medium on the cortical surface. CSD was
      visualized directly by using a fluorescent voltage-sensitive (VS) dye, whereas
      laser speckle contrast (LSC) imaging allowed the visualization of the
      corresponding CBF changes. In addition to the high temporal and spatial
      resolution of VS dye and LSC imaging, their novel combination allows to determine
      how CBF changes relate to a heterogeneous and evolving pattern of cellular
      depolarization, in any area of interest of the cortical region under study. This
      methodological development is especially pertinent and timely for investigations
      into the peri-lesion depolarizations that occur in models of focal brain injury,
      situations where their site of spontaneous elicitation and propagation pattern
      cannot be predicted. It should also help advance our knowledge in epilepsy, CBF
      pharmacology, and neurovascular coupling under normal and pathophysiological
      conditions.

PMID- 19100843
TI  - Intraoperative dynamic susceptibility contrast weighted magnetic resonance
      imaging (iDSC-MRI) - Technical considerations and feasibility.
AB  - DSC-MRI was applied intraoperatively during brain tumor removal. Immediately
      after presumed complete tumor resection an MRI including a dynamic susceptibility
      contrast T2-weighted EPI sequence was performed in 6 patients while the skull was
      still open using a flexible two-channel coil system at an intraoperative 1.5
      Tesla MR scanner. After an initial baseline period of this iDSC-MRI sequence a
      bolus of contrast agent was administered intravenously. Maps of relative regional
      blood flow (rCBF), blood volume (rCBV) and the mean transit time (MTT) were
      calculated. These maps were compared to preoperatively acquired DSC-MRI data. The
      extent of the resection was compared with the postoperative MRI performed 24 h
      after the operation. In five patients complete tumor removal was already achieved
      at the time of iDSC-MRI and no areas of elevated perfusion values adjacent to the
      resection cavity were found. Complete removal was again documented on the
      postoperatively performed MRI. In one case there was residual tumor that showed
      both contrast enhancement and identical perfusion ratios as in the preoperatively
      acquired data. Removal of the remaining tumor was performed. iDSC-MRI is
      technically feasible as there are no significant susceptibility artifacts. DSC
      MRI has been used to distinguish different tumor entities preoperatively and
      recurrent disease from radiation necrosis. Despite brain shift and thus
      invalidated preoperative image data or contrast leakage caused by intraoperative
      manipulation, iDCS-MRI furthermore reliably detects residual tumor
      intraoperatively at a timepoint where further resection is still possible and
      thus enables the neurosurgeon to complete the resection during the same
      procedure.

PMID- 19100844
TI  - The representation of object viewpoint in human visual cortex.
AB  - Understanding the nature of object representations in the human brain is critical
      for understanding the neural basis of invariant object recognition. However, the
      degree to which object representations are sensitive to object viewpoint is
      unknown. Using fMRI we employed a parametric approach to examine the sensitivity
      to object view as a function of rotation (0 degrees-180 degrees ), category
      (animal/vehicle) and fMRI-adaptation paradigm (short or long-lagged). For both
      categories and fMRI-adaptation paradigms, object-selective regions recovered from
      adaptation when a rotated view of an object was shown after adaptation to a
      specific view of that object, suggesting that representations are sensitive to
      object rotation. However, we found evidence for differential representations
      across categories and ventral stream regions. Rotation cross-adaptation was
      larger for animals than vehicles, suggesting higher sensitivity to vehicle than
      animal rotation, and was largest in the left fusiform/occipito-temporal sulcus
      (pFUS/OTS), suggesting that this region has low sensitivity to rotation.
      Moreover, right pFUS/OTS and FFA responded more strongly to front than back views
      of animals (without adaptation) and rotation cross-adaptation depended both on
      the level of rotation and the adapting view. This result suggests a prevalence of
      neurons that prefer frontal views of animals in fusiform regions. Using a
      computational model of view-tuned neurons, we demonstrate that differential
      neural view tuning widths and relative distributions of neural-tuned populations
      in fMRI voxels can explain the fMRI results. Overall, our findings underscore the
      utility of parametric approaches for studying the neural basis of object
      invariance and suggest that there is no complete invariance to object view in the
      human ventral stream.

PMID- 19100846
TI  - A complementary analytic approach to examining medial temporal lobe sources using
      magnetoencephalography.
AB  - Neuropsychological and neuroimaging findings reveal that the hippocampus is
      important for recognition memory. However, it is unclear when and whether the
      hippocampus contributes differentially to recognition of previously studied items
      (old) versus novel items (new), or contributes to a general processing
      requirement that is necessary for recognition of both types of information. To
      address this issue, we examined the temporal dynamics and spectral frequency
      underlying hippocampal activity during recognition of old/new complex scenes
      using magnetoencephalography (MEG). In order to provide converging evidence to
      existing literature in support of the potential of MEG to localize the
      hippocampus, we reconstructed brain source activity using the beamformer method
      and analyzed three types of processing-related signal changes by applying three
      different analysis methods: (1) Synthetic aperture magnetometry (SAM) revealed
      event related and non-event-related spectral power changes; (2) Inter-trial
      coherence (ITC) revealed time-locked changes in neural synchrony; and (3) Event
      related SAM (ER-SAM) revealed averaged event-related responses over time.
      Hippocampal activity was evident for both old and new information within the
      theta frequency band and during the first 250 ms following stimulus onset. The
      early onset of hippocampal responses suggests that general comparison processes
      related to recognition of new/old information may occur obligatorily.

PMID- 19100847
TI  - Domain-specific reorganization of semantic processing after extensive damage to
      the left temporal lobe.
AB  - We investigated with fMRI the cortical correlates of recovery of semantic
      processing in a patient (DL) with left temporal damage. Names of animals, plant,
      and artifacts (semantic conditions) and reversed words (baseline condition) were
      auditorily presented to the patient and nine control subjects in a category
      monitoring task. Data analyses showed large differences between the patterns of
      domain-specific semantic activation observed in DL and the control subjects,
      which could be attributed to a cortical reorganization compensating for the
      damaged part of the semantic processing system in DL. Such reorganization relied
      on three main mechanisms, first, upholding of a subset of the structurally intact
      domain-specific regions, second, functional changes (both decreases and
      increases) of the domain specificity in several structurally intact regions that
      are normally engaged in the domain-specific network and, third, recruitment of
      supplementary domain-specific areas. Thus, in DL, animal-specific processing
      engaged supplementary areas in the left lingual gyrus and right cuneus, which
      correspond to animal-specific regions usually engaged in more demanding semantic
      tasks whereas the supplementary areas recruited for artifact-specific processing
      within the left superior/middle occipital lobe and right angular gyrus probably
      are endowed with a related but not domain-specific, semantic function. In
      contrast, no supplementary area contributed to plant-specific processing in DL.
      These findings suggest that the pattern of cortical reorganization consecutive to
      damage to the semantic processing network depends on the particular domain
      specific function sustained by the damaged areas and the capacity of the
      remaining areas to assume this function.

PMID- 19100845
TI  - Long-term motor training induced changes in regional cerebral blood flow in both
      task and resting states.
AB  - Neuroimaging studies of functional activation often only reflect differentiated
      involvement of brain regions compared between task performance and control
      states. Signals common for both states are typically not revealed. Previous motor
      learning studies have shown that extensive motor skill training can induce
      profound changes in regional activity in both task and control states. To address
      the issue of brain activity changes in the resting-state, we explored long-term
      motor training induced neuronal and physiological changes in normal human
      subjects using functional magnetic resonance imaging (fMRI) and positron emission
      tomography (PET). Ten healthy subjects performed a finger movement task daily for
      four weeks, during which three sessions of fMRI images and two sessions of PET
      images were acquired. Using a classical data analysis strategy, we found that the
      brain activation increased first and then returned to the pre-training,
      replicating previous findings. Interestingly, we also observed that motor skill
      training induced significant increases in regional cerebral blood flow (rCBF) in
      both task and resting states as the practice progressed. The apparent decrease in
      activation may actually result from a greater increase in activity in the resting
      state, rather than a decrease in the task state. By showing that training can
      affect the resting state, our findings have profound implications for the
      interpretation of functional activations in neuroimaging studies. Combining
      changes in resting state with activation data should greatly enhance our
      understanding of the mechanisms of motor-skill learning.

PMID- 19100848
TI  - Phylogeny of Caragana (Fabaceae) based on DNA sequence data from rbcL, trnS-trnG,
      and ITS.
AB  - Phylogenetic relationships of 48 species of Caragana (Fabaceae: tribe Hedysareae)
      and one representative each of Astragalus, Calophaca, Halimodendron, and
      Hedysarum are estimated from DNA sequences of the rbcL gene, trnS-trnG intron and
      spacer, and ITS region. At least one representative of all five sections and 12
      series within Caragana are included. Analyses yielded strongly supported clades
      corresponding to sections Caragana, Bracteolatae, and Frutescentes. The species
      of section Jubatae are distributed among three strongly supported clades, i.e.,
      one with the species of section Bracteolatae, another with two species of section
      Spinosae, and a third as sister to section Frutescentes. All but the last of
      these six clades are corroborated by at least one unambiguously traced
      morphological character. The placement of the other four species of section
      Spinosae are not well supported and lack unambiguous morphological
      synapomorphies, and the samples of Calophaca and Halimodendron nest within
      Caragana with weak support.

PMID- 19100849
TI  - Re-examination of the phylogeny of Rhacophoridae (Anura) based on mitochondrial
      and nuclear DNA.
AB  - The phylogenetic relationships among rhacophorid frogs are under dispute. We use
      partial sequences of three mitochondrial (12S rRNA, 16S rRNA, and cytochrome b)
      and three nuclear protein-coding (Rag-1, rhodopsin exon 1, and tyrosinase exon 1)
      genes from 57 ingroup taxa and eight outgroup taxa to propose a hypothesis for
      phylogenetic relationships within Rhacophoridae. Our results support recognition
      of the genus Feihyla, and Chiromantis is the sister taxon to the clade formed by
      Feihyla, Polypedates and Rhacophorus. We place Aquixalus odontotarsus within
      Kurixalus, and the remaining species of Aquixalus and Philautus jinxiuensis into
      the genus Gracixalus. We give Philautus (Kirtixalus) the rank of genus and place
      Philautus menglaensis within it. The division of species groups among Chinese
      Rhacophorus needs revision, and a cryptic species is revealed within Rhacophorus
      nigropunctatus. Rhacophorus pingbianensis is considered a synonym of Rhacophorus
      omeimontis. The validity of Rhacophorus hui is confirmed by present molecular
      evidence.

PMID- 19100850
TI  - Activation of nociceptin opioid peptide (NOP) receptor impairs contextual fear
      learning in mice through glutamatergic mechanisms.
AB  - The present study investigated whether the selective nociceptin opioid peptide
      (NOP) receptor agonist, Ro64-6198, impairs acquisition of fear conditioning
      through glutamatergic mechanisms. Systemic administration of Ro64-6198 (0.3 and
      1mg/kg) or the non-competitive NMDA receptor antagonist, MK-801 (0.03 and
      0.1mg/kg) prior to conditioning severely impaired contextual but not cued fear
      learning in C57BL/6N mice. When administered together at sub-effective doses,
      Ro64-6198 (0.5mg/kg) and MK-801 (0.05mg/kg), synergistically impaired contextual
      fear learning, but left cued fear learning intact. We next used the immediate
      shock deficit paradigm (ISD) to examine the effects of Ro64-6198 and MK-801 on
      contextual memory formation in the absence of the foot-shock. As expected, naive
      mice that were shocked briefly after being placed in the training chamber
      displayed no contextual fear conditioning. This learning deficit was elevated by
      prior exposure of mice to the training context. Furthermore, administration of
      Ro64-6198 and MK-801, either separately at amnesic doses (1mg/kg and 0.1mg/kg,
      respectively) or concomitantly at sub-effective doses (0.5mg/kg and 0.05mg/kg,
      respectively) significantly reduced the facilitating effects of context
      preexposure. These findings demonstrate the existence of functional antagonism
      between NOP and NMDA receptors that predominantly contributes to modulation of
      conditioned fear learning which involves spatial-processing demands.

PMID- 19100851
TI  - Cognitive processing impairments in a supra-second temporal discrimination task
      in rats with cerebellar lesion.
AB  - The role of interpositus nuclei (IN) in timing in the sub-second range is well
      supported in eyeblink conditioning studies. Timing impairments shown in the
      seconds range in patients with intermediate cerebellar lesion, and known
      intermediate cerebellar cortex projection to IN raise the question of a possible
      involvement of IN in timing in the supra-second range as well. To address this
      question, we tested rats (Sprague-Dawley) given bilateral lesions of IN with
      Colchicine in a 2- vs. 8-s temporal discrimination task, followed by three daily
      sessions of a temporal bisection tests with five added intermediate non
      reinforced durations. IN lesioned rats showed normal acquisition of the temporal
      discrimination, but a transient impairment of temporal sensitivity during the
      bisection tests. In addition, their response latencies suggested a different
      behavioral strategy from that of control animals. Our results indicate that the
      IN of the cerebellum may not be critically involved in temporal processing in the
      2-8 s range, but may play a role in the cognitive processes that access temporal
      information in the mediation of choice behavior.

PMID- 19100852
TI  - Ecology and pathogenicity of gastrointestinal Streptococcus bovis.
AB  - Streptococcus bovis is an indigenous resident in the gastrointestinal tracts of
      both humans and animals. S. bovis is one of the major causes of bacterial
      endocarditis and has been implicated in the incidence of human colon cancer,
      possibly due to chronic inflammatory response at the site of intestinal
      colonization. Certain feeding regimens in ruminants can lead to overgrowth of S.
      bovis in the rumen, resulting in the over-production of lactate and capsular
      polysaccharide causing acute ruminal acidosis and bloat, respectively. There are
      multiple strategies in controlling acute lactic acidosis and bloat. The incidence
      of the two diseases may be controlled by strict dietary management. Gradual
      introduction of grain-based diets and the feeding of coarsely chopped roughage
      decrease the incidence of the two disease entities. Ionophores, which have been
      used to enhance feed conversion and growth rate in cattle, have been shown to
      inhibit the growth of lactic acid bacteria in the rumen. Other methods of
      controlling lactic acid bacteria in the ruminal environment (dietary
      supplementation of long-chain fatty acids, induction of passive and active immune
      responses to the bacteria, and the use of lytic bacteriophages) have also been
      investigated. It is anticipated that through continued in-depth ecological
      analysis of S. bovis the characteristics responsible for human and animal
      pathogenesis would be sufficiently identified to a point where more effective
      control strategies for the control of this bacteria can be developed.

PMID- 19100853
TI  - GFP sheds light on the infection process of avocado roots by Rosellinia necatrix.
AB  - In order to monitor Rosellinia necatrix infection of avocado roots, we generated
      a plasmid vector (pCPXHY1eGFP) constitutively expressing EGFP and developed a
      protoplast transformation protocol. Using this protocol, four R. necatrix
      isolates were efficiently transformed and were shown to stably express EGFP
      homogeneously while not having any observable effect on pathogenicity. Confocal
      laser scanning microscopy (CLSM) images of avocado roots infected with the highly
      virulent isolate CH53-GFP demonstrated that fungal penetration of avocado roots
      occurs simultaneously at several random sites, but it occurs preferentially in
      the crown region as well as throughout the lenticels and in the junctions between
      epidermal cells. Not only were R. necatrix hyphae observed invading the epidermal
      and cortical root cells, but they were also able to penetrate the primary and
      secondary xylem. Scanning electron microscopy (SEM) images allowed detailed
      visualisation of the hyphal network generated by invasion of R. necatrix through
      the epidermal, cortical and vascular cells, including hyphal anastomosis and
      branching points. To our knowledge, this is the first report describing the
      construction of GFP-tagged strains belonging to the genus Rosellinia for
      monitoring white root rot using CLSM and SEM.

PMID- 19100854
TI  - Exhaled nitric oxide, but not serum nitrite and nitrate, is a marker of
      interstitial lung disease in systemic sclerosis.
AB  - Nitric oxide metabolites (NOx) in serum, and alveolar concentration of NO
      (CA(NO)), are markers of inflammation and alveolitis, respectively, in systemic
      sclerosis (SSc). We prospectively evaluated the usefulness of both NOx and CA(NO)
      to assess lung involvement and skin fibrosis in SSc. Serum NOx, and CA(NO)
      measured by two different methods, namely the two-compartment (2CM) and the
      "trumpet" models (TM), were concomitantly assessed in 65 patients with SSc and 17
      healthy controls. Whilst serum NOx remained comparable between groups, CA(NO)
      were significantly higher in SSc patients (n=65, 6.7ppb; 4.8-9.7 and 5.9ppb; 3.9
      8.9) as compared with controls (n=17, 3.0ppb; 2.0-3.8 and 1.8ppb; 1.1-2.9,
      p<0.001, p<0.001) using the 2CM and the TM, respectively). CA(NO) from SSc
      patients with interstitial lung disease (ILD) (n=26, 8.6ppb; 6.5-10.9 and 8.5ppb;
      5.9-10.7) or pulmonary arterial hypertension (n=12, 7.3ppb; 6.5-10.4 and 6.9ppb;
      5.4-9.9) were significantly higher as compared with patients without ILD (n=27,
      4.9ppb; 3.8-6.5 and 4.7ppb; 2.8-5.7; p<0.001 and p<0.001) using the 2CM and the
      TM, respectively). CA(NO) assessed either by the 2CM or the trumpet model were
      directly related to the extent of ILD and inversely related to DLCO. There was no
      correlation between NOx and ILD, or DLCO. Neither CA(NO) nor NOx was correlated
      with skin fibrosis and no relationship was found between CA(NO) and NOx. Alveolar
      concentration of NO, but not serum NOx, closely correlates with the extent of ILD
      in patients with systemic sclerosis. Neither parameter, however, is related to
      skin fibrosis.

PMID- 19100855
TI  - Homocysteine decreases platelet NO level via protein kinase C activation.
AB  - Hyperhomocysteinaemia has been associated with increased risk of thrombosis and
      atherosclerosis. Homocysteine produces endothelial injury and stimulates platelet
      aggregation. Several molecular mechanisms related to these effects have been
      elucidated. The study aimed to deeply investigate the homocysteine effect on
      nitric oxide formation in human platelets. The homocysteine-induced changes on
      nitric oxide, cGMP, superoxide anion levels and nitrotyrosine formation were
      evaluated. The enzymatic activity and the phosphorylation status of endothelial
      nitric oxide synthase (eNOS) at thr495 and ser1177 residues were measured. The
      protein kinase C (PKC), assayed by immunofluorescence confocal microscopy
      technique and by phosphorylation of p47pleckstrin, and NADPH oxidase activation,
      tested by the translocation to membrane of the two cytosolic subunits p47(phox)
      and p67(phox), were assayed. Results show that homocysteine reduces platelet
      nitric oxide and cGMP levels. The inhibition of eNOS activity and the stimulation
      of NADPH oxidase primed by PKC appear to be involved. PKC stimulates the eNOS
      phosphorylation of the negative regulatory residue thr495 and the
      dephosphorylation of the positive regulatory site ser1177. GF109203X and U73122,
      PKC and phospholipase Cgamma2 pathway inhibitors, respectively, reverse this
      effect. Moreover, homocysteine stimulates superoxide anion elevation and NADPH
      oxidase activation. These effects are significantly decreased by GF109203X and
      U73122, suggesting the involvement of PKC in NADPH oxidase activation.
      Homocysteine induces formation of the peroxynitrite biomarker nitrotyrosine.
      Taken together these results suggest that the homocysteine-mediated responses
      leading to nitric oxide impairment are mainly coupled to PKC activation. Thus
      homocysteine stimulates platelet aggregation and decreases nitric oxide
      bioavailability.

PMID- 19100856
TI  - Introduction of an NADH regeneration system into Klebsiella oxytoca leads to an
      enhanced oxidative and reductive metabolism of glycerol.
AB  - Redox cofactors play crucial roles in the metabolic and regulatory network of
      living organisms. We reported here the effect of introducing a heterogeneous NADH
      regeneration system into Klebsiella oxytoca on cell growth and glycerol
      metabolism. Expression of fdh gene from Candida boidinii in K. oxytoca resulted
      in higher intracellular concentrations of both NADH and NAD(+) during the
      fermentation metaphase, with the ratio of NADH to NAD(+) unaltered and cell
      growth unaffected, interestingly different from that in engineered Escherichia
      coli, Lactococcus lactis, and others. Metabolic flux analysis revealed that
      fluxes to 1,3-propanediol, ethanol, and lactate were all increased, suggesting
      both the oxidative and reductive metabolisms of glycerol were enhanced. It
      demonstrates that in certain microbial system NADH availability can be increased
      with NADH to NAD(+) ratio unaltered, providing a new strategy to improve the
      metabolic flux in those microorganisms where glycolysis is not the only central
      metabolic pathways.

PMID- 19100857
TI  - Treatment of chronically Trypanosoma cruzi-infected mice with a CCR1/CCR5
      antagonist (Met-RANTES) results in amelioration of cardiac tissue damage.
AB  - The comprehension of the molecular mechanisms leading to Trypanosoma cruzi
      elicited heart dysfunction might contribute to design novel therapeutic
      strategies aiming to ameliorate chronic Chagas disease cardiomyopathy. In C3H/He
      mice infected with the low virulence T. cruzi Colombian strain, the persistent
      cardiac inflammation composed mainly of CCR5(+) T lymphocytes parallels the
      expression of CC-chemokines in a pro-inflammatory IFN-gamma and TNF-alpha milieu.
      The chronic myocarditis is accompanied by increased frequency of peripheral
      CCR5(+)LFA-1(+) T lymphocytes. The treatment of chronically T. cruzi-infected
      mice with Met-RANTES, a selective CCR1/CCR5 antagonist, led to a 20-30% decrease
      in CD4(+) cell numbers as well as IL-10, IL-13 and TNF-alpha expression. Further,
      Met-RANTES administration impaired the re-compartmentalization of the activated
      CD4(+)CCR5(+) lymphocytes. Importantly, Met-RANTES treatment resulted in
      significant reduction in parasite load and fibronectin deposition in the heart
      tissue. Moreover, Met-RANTES treatment significantly protected T. cruzi-infected
      mice against connexin 43 loss in heart tissue and CK-MB level enhancement,
      markers of heart dysfunction. Thus, our results corroborate that therapeutic
      strategies based on the modulation of CCR1/CCR5-mediated cell migration and/or
      effector function may contribute to cardiac tissue damage limitation during
      chronic Chagas disease.

PMID- 19100858
TI  - Vav1: a hematopoietic signal transduction molecule involved in human
      malignancies.
AB  - Vav1 encodes a unique protein with several motifs known to play a role in
      tyrosine mediated signal transduction, including a DBL homology (DH) domain, a
      pleckstrin homology (PH) domain, a Src homology 2 (SH2) domain, and two Src
      homology 3 (SH3) domains. Physiological Vav1 expression is restricted to the
      hematopoietic system, where it functions primarily as a specific GDP/GTP
      nucleotide exchange factor (GEF), a function strictly regulated by tyrosine
      phosphorylation. In hematopoietic cells, Vav1 is phosphorylated following cell
      surface receptor activation, triggering re-organization of the cytoskeleton and
      regulation of other cellular functions including transcription, cytokine
      production, cell cycle progression, and Ca(2+) mobilization. Vav1 also functions
      as an adapter, facilitating interaction between other proteins. A truncated Vav1
      was first isolated as an oncogene, and its wild-type form has recently been
      implicated in mammalian malignancies. These properties make Vav1 a promising
      target for new therapeutic approaches to organ transplantation and cancer
      therapy.

PMID- 19100859
TI  - Measurement of oxidative DNA damage induced by mainstream cigarette smoke in
      cultured NCI-H292 human pulmonary carcinoma cells.
AB  - Cigarette smoke is a complex dynamic mixture of more than 4800 chemicals
      distributed between the particulate and vapour phases. It is widely acknowledged
      that cigarette smoke is capable of causing oxidative damage in DNA, either
      directly or through generation of reactive oxygen species. In this study, we have
      used a novel system for exposing cultured NCI-H292 human pulmonary carcinoma
      cells at the air-liquid interface, to investigate the potential effects of
      cigarette smoke on oxidative DNA damage by use of the modified comet assay with
      formamidopyrimidine N-glycosylase (FPG) and endonuclease III (Endo III) to reveal
      purine and pyrimidine lesions, respectively. The results demonstrate that NCI
      H292 cells exposed to mainstream cigarette smoke from Kentucky reference
      cigarettes show considerable DNA damage in terms of strand-breaks (SBs), alkali
      labile sites (ALS) and oxidative DNA lesions. Initial measurements of FPG
      sensitive oxidative lesions were confounded by high levels of SBs and ALS. Strand
      breaks, but not oxidative lesions are repaired during a 20-h recovery period,
      which allows the semi-quantitative measurement of FPG-sensitive oxidative DNA
      lesions. We also conclude that mainstream cigarette smoke does not generate
      increased levels of Endo III-sensitive oxidative DNA lesions, or that they are
      not distinguishable from SBs and ALS in vitro in this system. Moreover, we
      demonstrate the viability and versatility of this exposure system in combination
      with in vitro techniques as an investigative tool for damage induced by cigarette
      smoke and smoke constituents.

PMID- 19100860
TI  - Dose-dependent alterations in gene expression in mouse liver induced by
      diethylnitrosamine and ethylnitrosourea and determined by quantitative real-time
      PCR.
AB  - We examined the dose-dependency of gene expression changes for 51 genes in mouse
      liver treated with two N-nitroso genotoxic hepatocarcinogens, diethylnitrosamine
      (DEN) and ethylnitrosourea (ENU) by quantitative real-time PCR (qPCR). DEN (3, 9,
      27 and 80mg/kg bw) or ENU (6, 17, 50 and 150mg/kg bw) was injected
      intraperitoneally into groups of five male 9-week-old B6C3F(1) mice and the
      livers were dissected after 4h and 28 days. Total RNA from pooled livers was
      reverse-transcribed to cDNA and the amount of each gene was quantified by qPCR.
      Results were analyzed by hierarchical and k-means clustering and ingenuity
      pathway analysis (IPA). The most characteristic result was a similar dose
      dependency of gene expression changes with DEN and ENU. Twenty-one genes
      exhibited a distinct dose-dependent increase in expression at 4h for both
      carcinogens [Bax, Btg2, Ccng1, Cdkn1a, Cyp4a10, Cyp21a1, Fos, Gadd45b, Gdf15,
      Hmox1, Hspb1, Isg20l1, Jun, Mbd1, Mdm2, Myc, Net1, Plk2, Ppp1r3c, Rcan1 and
      Tubb2c], although the increase in gene expression due to ENU was generally weaker
      than that due to DEN. Only Gdf15 showed a dose-dependent increase in expression
      at 28 days for both carcinogens. The differences between DEN and ENU were in the
      expression of additional genes (7 for DEN and 8 for ENU). IPA extracted five gene
      networks: Network-1 included genes related to cancer and cell cycle arrest and
      associated with Bax, Btg2, Ccng1, Cdkn1a, Gadd45b, Gdf15, Hspb1, Mdm2 and Plk2
      and Network-2 was related to DNA replication, recombination, repair and cell
      death and associated with Cyp21a1, Gdf15, Ppp1r3c, Rcan1 and Tubb2c. The present
      results show a distinct dose-dependency of gene expression changes induced by DEN
      and ENU. These changes were associated with cancer, cell cycle arrest, DNA
      replication, recombination, repair and cell death and were seen not only at 4h
      but also, for some, at 28 days after administration.

PMID- 19100861
TI  - A lifetime passion for micronucleus cytome assays--reflections from Down Under.
AB  - A brief account of an improbable career in the field of genetic toxicology is
      given, extending from my early years in Malta through a life-changing decision to
      study in Australia (Down Under). I describe the circumstances that led to the
      discovery of the cytokinesis-block micronucleus (CBMN) assay and its evolution
      into a cytome assay of chromosome breakage and loss (micronuclei), asymmetrical
      chromosome rearrangements or telomere end fusions (nucleoplasmic bridges), gene
      amplification (nuclear buds), cell death (necrosis, apoptosis) and cytostasis
      (nuclear division index). This paper also describes the role of my laboratory in
      the beginning of the HUMN project, its achievements, and the applications of CBMN
      cytome assays in the fields of radiation biology, genetic toxicology,
      epidemiology, biodosimetry and genome health nutrigenomics, leading to the Genome
      Health Clinic concept. Along the way I mention my encounters with some of the
      influential people in the field of mutagenesis who provided me with the
      motivation and guidance needed to realise these achievements. I hope this account
      provides some inspiration to the next generation of scientists who may be
      fortunate to see the realisation of the application of the principles of
      mutagenesis in health optimisation or disease prevention and eventually in
      mainstream medicine.

PMID- 19100862
TI  - Relaxation induced by calcium ionophore is impaired in carotid arteries from 2K
      1C rats due to failed effect of nitric oxide on the smooth muscle cells.
AB  - Vascular endothelium generates nitric oxide (NO) in large vessels and induces
      relaxation of vascular smooth muscle cells (VSMC). The aim of this study was to
      evaluate the contribution of NO produced in the endothelial cells (EC) to the
      relaxation induced by the Ca2+ ionophore A23187 and whether this relaxation is
      impaired in renal hypertensive (2K-1C) rat arteries. Concentration-effect curves
      for A23187 were constructed in intact endothelium isolated carotid rings from 2K
      1C and normotensive (2K) in the absence or in the presence of the extracellular
      NO scavenger haemoglobin or inhibitors of NO-synthase (NOS, L-NOARG), guanylyl
      cyclase (GC, ODQ). In carotid rings loaded with Fluo-3AM, both EC and VSMC were
      simultaneously imaged by a confocal microscope and [Ca2+]c was derived from
      fluorescence intensities (IF). The maximal relaxation (ME) induced by A23187 was
      lower in 2K-1C than in 2K arteries. A23187-induced relaxation was abolished by
      haemoglobin and L-NOARG in both groups. ODQ reduced the ME to A23187 in 2K and
      abolished its relaxation in 2K-1C. A23187 increased [Ca2+]c in a similar way in
      2K and 2K-1C EC, and decreased [Ca2+]c in VSMC, which effect was higher in 2K
      than in 2K-1C arteries. L-NOARG inhibited the effect of A23187 in VSMC from 2K
      and abolished it in 2K-1C rats. On the other hand, L-NOARG did not modify the
      effect of A23187 in EC from 2K and 2K-1C rats. The basal content of cGMP was
      higher in 2K than in 2K-1C arterial rings that was similarly increased by A23187.
      In conclusion, the Ca2+ ionophore A23187 increases Ca2+, activates NOS and NO
      production in the EC activating GC in VSMC and [Ca2+]c decrease. All these
      effects are higher in 2K, which contribute to the impaired relaxation to A23187
      in 2K-1C rat arteries.

PMID- 19100863
TI  - Structure, dynamics and function of Leishmania genome: resolving the puzzle of
      infection, genetics and evolution?
AB  - We review and discuss here the specificity and contribution of genome (re
      )arrangement studies for the exploration of genetic diversity among Leishmania.
      We show how the early molecular karyotyping studies generated an original
      perception of the genetics and evolution of these Protozoa, while providing some
      possible explanations on the parasite diverse phenotypes (drug resistance,
      pathogenicity...). We compare the results with the enormous amount of data
      provided by the recent genome sequencing projects, so far focused on one strain
      per genus/species. We highlight the relevance of parallel sequencing of different
      strains of a same species, now made possible by the new sequencing technologies.
      We recommend paying a particular attention to variation in gene copy number, a
      feature showed by the karyotyping studies to be extremely informative.

PMID- 19100864
TI  - Detection of the Tim-3 ligand, galectin-9, inside the allograft during a
      rejection episode.
AB  - INTRODUCTION: Tim-3 is a Th1 lymphocytes membrane protein with inhibitory
      function. Its ligand, galectin-9, was recently identified and it is expressed in
      some lymphocyte subpopulation. In addition, endothelial cells and fibroblasts can
      also express galectin-9 according to the local cytokine milieu. Both molecules
      can act as important regulatory tools in the immune system. AIM: Evaluate the
      expression of these immunoregulatory molecules inside kidney allografts during
      acute rejection episodes. METHODS: By using a quantitative polymerase chain
      reaction assay, we measured the levels of messenger RNA (mRNA) for galectin-9 and
      Tim-3 in 21 samples obtained at allograft nephrectomy. Five samples received the
      histological diagnosis of acute non-vascular rejection (ANVR), twelve of acute
      vascular rejection (AVR), and five of loss of non-immune cause (LNIC; as
      control). As cytolytic response markers we measured mRNA levels of granzyme B,
      interferon-gamma and perforin. The statistic analysis was performed using one way
      analysis of variance (ANOVA) and Pearson correlation. RESULTS: The mean levels of
      Tim-3 mRNA expression were 13.99+/-6.99 for LNIC, 48.13+/-54.47 for RACNV and
      238.63+/-333.14 for RAV (p=0.004). For galectin-9, the mean values were 0.57+/
      0.49 for LNIC, 0.66+/-0.36 for RACNV and 2.34+/-1.62 for RAV (p=0.006).
      Furthermore, there was a positive correlation between both molecules (r=0.526,
      p=0.016). Also, granzyme B, perforin and interferon-gamma mRNA expression were
      different among the three groups. CONCLUSION: Messenger RNA level expressions of
      all the studied molecules were higher inside allografts with more severe
      rejection. Moreover, there was a positive correlation between galectin-9 and Tim
      3 mRNA levels. The simultaneous expression of galectin-9 and Tim-3 may indicate
      an immunoregulatory function, during the ongoing cytotoxic response.

PMID- 19100865
TI  - Interaction between the mismatch repair and nucleotide excision repair pathways
      in the prevention of 5-azacytidine-induced CG-to-GC mutations in Escherichia
      coli.
AB  - 5-Azacytidine induces CG-to-GC transversion mutations in Escherichia coli. The
      results presented in this paper provide evidence that repair of the drug-induced
      lesions that produce these mutations involves components of both the mismatch
      repair and nucleotide excision repair systems. Strains deficient in mutL, mutS,
      uvrA, uvrB or uvrC all showed an increase in mutation in response to 5
      azacytidine. Using a bacterial two-hybrid assay, we showed that UvrB interacts
      with MutL and MutS in a drug-dependent manner, while UvrC interacts with MutL
      independent of drug. We suggest that 5-azacytidine-induced mismatches recruit
      MutS and MutL, but are poorly processed by mismatch repair. Instead, the stalled
      MutS-MutL complex recruits the Uvr proteins to complete repair.

PMID- 19100866
TI  - Modulation of the effects of tropomyosin on actin and myosin conformational
      changes by troponin and Ca2+.
AB  - The molecular mechanisms by which troponin (TN)-tropomyosin (TM) regulates the
      myosin ATPase cycle were investigated using fluorescent probes specifically bound
      to Cys36 of TM, Cys707 of myosin subfragment-1, and Cys374 of actin incorporated
      into ghost muscle fibers. Intermediate states of actomyosin were simulated by
      using nucleotides and non-hydrolysable ATP analogs. Multistep changes in mobility
      and spatial arrangement of SH1 helix of myosin motor domain and actin subdomain-1
      during the ATPase cycle were observed. Each intermediate state of actomyosin
      induced a definite conformational state and specific position of TM strands on
      the surface of thin filament. TM increased the amplitude of myosin SH1 helix and
      actin subdomain-1 movements at transition from weak- to strong-binding states
      shifting to the center of thin filament at strong-binding and to the periphery of
      thin filament at weak-binding states. TN modulated those movements in a capital
      ES, Cyrillicsmall a, Cyrillic(2+)-dependent manner. At high-Ca(2+), TN enhanced
      the effect of TM on SH1 helix and subdomain-1 movements by transferring TM
      further to the center of thin filament at strong-binding states. In contrast, at
      low-Ca(2+), TN inhibited the effect of TM movements, "freezing" actin structure
      in "OFF" state and TM in the position typical for weak-binding states, resulting
      in disturbing the interplay of actin and myosin.

PMID- 19100867
TI  - Multidrug efflux transporters in the MATE family.
AB  - The MATE (Multidrug And Toxic Compound Extrusion) family is the most recently
      categorized one among five multidrug efflux transporter families. As far as we
      know, about twenty MATE transporters have been characterized so far. According to
      the information in sequence databases, huge numbers of MATE transporters seem to
      be present in various microorganisms. In this review, we would like to summarize
      the properties of the MATE-family transporters.

PMID- 19100868
TI  - Role of protein surface charge in monellin sweetness.
AB  - A small number of proteins have the unusual property of tasting intensely sweet.
      Despite many studies aimed at identifying their sweet taste determinants, the
      molecular basis of protein sweetness is not fully understood. Recent mutational
      studies of monellin have implicated positively charged residues in sweetness. In
      the present work, the effect of overall net charge was investigated using the
      complementary approach of negative charge alterations. Multiple substitutions of
      Asp/Asn and Glu/Gln residues radically altered the surface charge of single-chain
      monellin by removing six negative charges or adding four negative charges.
      Biophysical characterization using circular dichroism, fluorescence, and two
      dimensional NMR demonstrates that the native fold of monellin is preserved in the
      variant proteins under physiological solution conditions although their stability
      toward chemical denaturation is altered. A human taste test was employed to
      determine the sweetness detection threshold of the variants. Removal of negative
      charges preserves monellin sweetness, whereas added negative charge has a large
      negative impact on sweetness. Meta-analysis of published charge variants of
      monellin and other sweet proteins reveals a general trend toward increasing
      sweetness with increasing positive net charge. Structural mapping of monellin
      variants identifies a hydrophobic surface predicted to face the receptor where
      introduced positive or negative charge reduces sweetness, and a polar surface
      where charges modulate long-range electrostatic complementarity.

PMID- 19100869
TI  - Characteristics of mutants designed to incorporate a new ion pair into the
      structure of a cold adapted subtilisin-like serine proteinase.
AB  - Structural comparisons of VPR, a subtilisin-like serine proteinase from a
      psychrotrophic Vibrio species and a thermophilic homologue, aqualysin I, have led
      us to hypothesize about the roles of different residues in the temperature
      adaptation of the enzymes. Some of these hypotheses are now being examined by
      analysis of mutants of the enzymes. The selected substitutions are believed to
      increase the stability of the cold adapted enzyme based on structural analysis of
      the thermostable structure. We report here on mutants, which were designed to
      incorporate an ion pair into the structure of VPR. The residues Asp17 and Arg259
      are assumed to form an ion pair in aqualysin I. The cold adapted VPR contains Asn
      (Asn15) and Lys (Lys257) at corresponding sites in its structure. In VPR, Asn 15
      is located on a surface loop with its side group pointing towards the side chain
      of Lys257. By substituting Asn15 by Asp (N15D) it was considered feasible that a
      salt bridge would form between the oppositely charged groups. To mimic further
      the putative salt bridge from the thermophile enzyme the corresponding double
      mutant (N15D/K257R) was also produced. The N15D mutation increased the thermal
      stability of VPR by approximately 3 degrees C, both in T(50%) and T(m). Addition
      of the K257R mutation did not however, increase the stability of the double
      mutant any further. Despite this stabilization of the VPR mutants the catalytic
      activity (k(cat)) against the substrate Suc-AAPF-NH-Np was increased in the
      mutants. Molecular dynamics simulations on wild type and the two mutant proteins
      suggested that indeed a salt bridge was formed in both cases. Furthermore, a
      truncated form of the N15D mutant (N15DDeltaC) was produced, lacking a 15 residue
      long C-terminal extended sequence not present in the thermophilic enzyme. In wild
      type VPR this supposedly moveable, negatively charged arm on the protein molecule
      might interfere with the new salt bridge introduced as a result of the N15D
      mutation. Removal of the C-terminal arm improved the thermal stability (T(m)
      approximately +1.5 degrees C) of the truncated enzyme (VPRDeltaC) as compared to
      the wild type VPR. Introduction of the N15D substitution into VPRDeltaC improved
      the thermal stability further by about 3 degrees C, or to about the same extent
      as in the wild type. However, contrary to what was observed for the wild type,
      the introduction of the putative salt bridge did not affect the catalytic
      properties (k(cat)) of the C-terminal truncated enzyme.

PMID- 19100870
TI  - Heterooligomeric complexes formed by human small heat shock proteins HspB1
      (Hsp27) and HspB6 (Hsp20).
AB  - Formation of heterooligomeric complexes of human small heat shock proteins (sHsp)
      HspB6 (Hsp20) and HspB1 (Hsp27) was analyzed by means of native gel
      electrophoresis, analytical ultracentrifugation, chemical cross-linking and size
      exclusion chromatography. HspB6 and HspB1 form at least two different complexes
      with apparent molecular masses 100-150 and 250-300 kDa, and formation of
      heterooligomeric complexes is temperature dependent. These complexes are highly
      mobile, easily exchange their subunits and are interconvertible. The
      stoichiometry of HspB1 and HspB6 in both complexes is close to 1/1 and smaller
      complexes are predominantly formed at low, whereas larger complexes are
      predominantly formed at high protein concentration. Formation of heterooligomeric
      complexes does not affect the chaperone-like activity of HspB1 and HspB6 if
      insulin or skeletal muscle F-actin was used as model protein substrates. After
      formation of heterooligomeric complexes the wild type HspB1 inhibits the rate of
      phosphorylation of HspB6 by cAMP-dependent protein kinase. The 3D mutant
      mimicking phosphorylation of HspB1 also forms heterooligomeric complexes with
      HspB6, but is ineffective in inhibition of HspB6 phosphorylation. Inside of
      heterooligomeric complexes HspB6 inhibits phosphorylation of HspB1 by MAPKAP2
      kinase. Thus, in heterooligomeric complexes HspB6 and HspB1 mutually affect the
      structure of each other and formation of heterooligomeric complexes might
      influence diverse processes depending on small heat shock proteins.

PMID- 19100871
TI  - Assembly and function of AsGlu2 fibrillar multimer of oat beta-glucosidase.
AB  - Oat beta-glucosidase in plastid exists as a long fibrillar structure of AsGlu1
      homomultimer (type I) and heteromultimer of AsGlu1 and AsGlu2 (type II). In spite
      of the high amino acid sequence homology of AsGlu1 and AsGlu2, AsGlu1 assembles
      into the fibrillar multimers but AsGlu2 forms a dimer when expressed in E. coli.
      A swapping analysis of AsGlu2 cDNA with AsGlu1 cDNA indicated that the C-terminal
      segment of AsGlu1 was critical for the fibrillar multimerization. A single
      substitution of glutamic acid-495 of AsGlu2 in the C-terminal region with lysine,
      an AsGlu1 counterpart amino acid for the glutamic acid-495, assembled the AsGlu2
      into fibrillar homomultimers. The mutant AsGlu2 homomultimer was highly stable
      and had relatively faster electric mobility in native gel than the AsGlu1
      homomultimer. Multimerization increased enzyme affinity to substrates.

PMID- 19100872
TI  - A 3.1-Mb microdeletion of 3p21.31 associated with cortical blindness, cleft lip,
      CNS abnormalities, and developmental delay.
AB  - We report a 3.1-Mb de novo deletion of 3p21.31 in a 3.5-year-old female with
      cortical blindness, cleft lip, CNS abnormalities, and gross developmental delays.
      Examination of the region showed approximately 80 genes to be involved in the
      deletion. Functional analysis of the deleted genes suggests that several of them
      may be important in normal neuronal maturation and function. Thus,
      haploinsufficiency of one or more of these genes could potentially contribute to
      the observed phenotype. Our patient does not have clinical features that overlap
      completely with either proximal or distal 3p deletions, suggesting that the
      deletion seen in our patient leads to a distinct clinical phenotype not described
      previously.

PMID- 19100873
TI  - Identification of novel candidate protein biomarkers for the post-polio syndrome 
      implications for diagnosis, neurodegeneration and neuroinflammation.
AB  - Survivors of poliomyelitis often develop increased or new symptoms decades after
      the acute infection, a condition known as post-polio syndrome (PPS). The
      condition affects 20-60% of previous polio patients, making it one of the most
      common causes of neurological deficits worldwide. The underlying pathogenesis is
      not fully understood and accurate diagnosis is not feasible. Herein we
      investigated whether it was possible to identify proteomic profile aberrations in
      the cerebrospinal fluid (CSF) of PPS patients. CSF from 15 patients with well
      defined PPS were analyzed for protein expression profiles. The results were
      compared to data obtained from nine healthy controls and 34 patients with other
      non-inflammatory diseases which served as negative controls. In addition, 17
      samples from persons with secondary progressive multiple sclerosis (SPMS) were
      added as relevant age-matched references for the PPS samples. The CSF of persons
      with PPS displayed a disease-specific and highly predictive (p=0.0017)
      differential expression of five distinct proteins: gelsolin, hemopexin,
      peptidylglycine alpha-amidating monooxygenase, glutathione synthetase and
      kallikrein 6, respectively, in comparison with the control groups. An independent
      ELISA confirmed the increase of kallikrein 6. We suggest that these five proteins
      should be further evaluated as candidate biomarkers for the diagnosis and
      development of new therapies for PPS patients.

PMID- 19100874
TI  - Calreticulin mediated glucocorticoid receptor export is involved in beta-catenin
      translocation and Wnt signalling inhibition in human osteoblastic cells.
AB  - Wnt signalling pathway is a multicomponent cascade involving interaction of
      several proteins and found to be important for development and function of
      various cells and tissues. There is increasing evidence that the Wnt/beta-catenin
      pathway constitutes also one of the essential molecular mechanisms controlling
      the metabolic aspects of osteoblastic cells. However, in bone, glucocorticoids
      (GCs) have been reported to weaken Wnt signalling. Therefore, the aim of this
      study was to characterize the mechanisms behind the cross-talk of these two
      signalling pathways in human osteoblastic cells. Based on our findings, liganded
      glucocorticoid receptor (GR) modulated Wnt signalling pathway by decreasing beta
      catenin's nuclear accumulation and increasing its relocalization to cell
      membranes rather than affecting its degradation in human osteoblastic cells. The
      region of GR responsible for this inhibitory effect located into an area, which
      harbours the DNA binding as well as nuclear export domains. In further studies, a
      chaperone protein calreticulin (CRT), known to bind the DNA binding domain of GR
      and regulate receptor export, was found to be involved in the GR-mediated
      downregulation of Wnt signalling: GR mutants containing incomplete CRT binding
      sites were not able to translocate beta-catenin to cell surface. In addition, the
      inhibitory effect of GCs on endogenous Wnt target gene, cyclin D1, was abolished,
      when the expression of CRT was attenuated by the RNAi technique. Furthermore, GR
      and beta-catenin were shown to exist in the same immunocomplex, while interaction
      between CRT and beta-catenin was observed only in the presence of GR as a
      mediator molecule. In addition, the GR mutant lacking CRT binding ability
      impaired the complex formation between beta-catenin and CRT. Together with GR,
      beta-catenin could thus be co-transported from the nucleus in a CRT-dependent
      way. These observations represent a novel mechanism for GCs to downregulate Wnt
      signalling pathway in human osteoblastic cells. Knowledge of these molecular
      mechanisms is important for understanding the network of multiple signalling
      cascades in bone environment. Functional Wnt signalling pathway is a prerequisite
      for proper osteoblastogenesis, and this modulative cross-talk between the steroid
      pathway and Wnt cascade could therefore explain some of the two-edged effects of
      GCs on osteoblastic differentiation and function.

PMID- 19100875
TI  - Recent advances in immobilized enzymatic reactors and their applications in
      proteome analysis.
AB  - Immobilized enzymatic reactors recently have drawn much attention because of the
      striking advantages, such as high substrate turnover rate and ease in coupling
      with the separation and detection systems. Carrier materials, which have great
      effects on the development of the immobilized enzymatic reactors, have always
      being the focus of study. In this paper, the contributions, mainly in the last 5
      years, on the enzymatic reactors and their applications in proteome study are
      reviewed, with some newly developed inorganic and organic carriers for enzyme
      immobilization described in details. Moreover, the hyphenation of immobilized
      enzymatic reactors with the separation and identification systems is also
      summarized. By reviewing these achievements, it could be seen that enzymatic
      reactors have very bright future, especially in proteome analysis.

PMID- 19100876
TI  - Characterization of rhodamine B hydroxylamide as a highly selective and sensitive
      fluorescence probe for copper(II).
AB  - Rhodamine B hydroxylamide (1) is characterized as a highly selective and
      sensitive fluorescence probe for Cu(2+). Under the optimized conditions, the
      probe exhibits specific absorbance-on and fluorescence-on responses to Cu(2+)
      only. This remarkable property may allow Cu(2+) to be detected directly in the
      presence of the other transition metal ions, and such an application has been
      demonstrated to human serum. The reaction mechanism is also investigated and
      proposed as that the hydroxylamide group of 1 binds Cu(2+), and the subsequent
      complexation of Cu(2+) displays a high catalytic activity for the hydrolytic
      cleavage of the amide bond, causing the release of fluorophore (rhodamine B) and
      thereby the retrievement of absorbance and fluorescence. The recovered
      fluorescence intensity is proportional to the concentration of Cu(2+) in the
      range 1-20 microM. The detection limit for Cu(2+) is 33 nM (k=3). The reaction
      mechanism described here may be useful for developing excellent spectroscopic
      probes with cleavable active bonds for other analytes.

PMID- 19100877
TI  - Enhanced electrochemical activity of redox-labels in multi-layered protein films
      on indium tin oxide nanoparticle-based electrode.
AB  - Facile electrical communication between redox-active labeling molecules and
      electrode is essential in the electrochemical detection of bio-affinity
      reactions. In this report, nanometer-sized indium tin oxide (ITO) particles were
      employed in the fabrication of porous thick film electrodes to enhance the
      otherwise impeded electrochemical activity of redox labels in multi-layered
      protein films, and to enable quantitative detection of avidin/biotin binding
      interaction. To carry out the affinity reaction, avidin immobilized on an ITO
      electrode was reacted with mouse IgG labeled with both biotin and ruthenium Tris
      (2,2'-bipyridine) (Ru-bipy). The binding reaction between avidin and biotin was
      detected by the catalytic voltammetry of Ru-bipy in an oxalate-containing
      electrolyte. On sputtered ITO thin film electrode, although a single layer of Ru
      bipy labeled avidin exhibited substantial anodic current, attaching the label to
      the outer IgG layer of the avidin/biotin-IgG binding pair resulted in almost
      complete loss of the signal. However, electrochemical current was recovered on
      ITO film electrodes prepared from nanometer-sized particles. The surface of the
      nanoparticle structured electrode was found by scanning electron microscopy to be
      very porous, and had twice as much surface binding capacity for avidin as the
      sputtered electrode. The results were rationalized by the assumption of different
      packing density of avidin inner layer on the two surfaces, and consequently
      different electron transfer distance between the electrode and Ru-bipy on the IgG
      outer layer. A linear relationship between electrochemical current and IgG
      concentration was obtained in the range of 40-4000 nmol L(-1) on the nanoparticle
      based electrode. The approach can be employed in the electrochemical detection of
      immunoassays using non-enzymatic redox labels.

PMID- 19100878
TI  - Microsensor in vivo monitoring of oxidative burst in oilseed rape (Brassica napus
      L.) leaves infected by Sclerotinia sclerotiorum.
AB  - Oxidative burst is the rapid and transient production of large amounts of
      reactive oxygen species, including superoxide anion, hydrogen peroxide
      (H(2)O(2)), and hydroxyl radical. A rapid and simple technique was employed for
      in vivo detection of oxidative burst in oilseed rape (Brassica napus L.) leaves,
      using a modified electrode. Platinum (Pt) micro-particles were dispersed on a Pt
      electrode, coated with a poly (o-phenylenediamine) film. This exhibited high
      sensitivity, selectivity and stability in H(2)O(2) detection. Amperometry was
      used to obtain satisfactory linear relationships between reductive current
      intensities and H(2)O(2) concentrations at -0.1 V potential in different
      electrolytes. This electrode was used in vivo to detect oxidative burst in
      oilseed rape following fungal infection. Oxidative bursts induced by infection of
      the fungal pathogen Sclerotinia sclerotiorum (Lib.) de Bary exhibited notably
      different mechanisms between a susceptible and a resistant glucose oxidase
      transgenic genotype.

PMID- 19100879
TI  - Comparison of standard and reaction cell inductively coupled plasma mass
      spectrometry in the determination of chromium and selenium species by HPLC-ICP
      MS.
AB  - Elemental speciation is becoming a common analytical procedure for geochemical
      investigations. The various redox species of environmentally relevant metals can
      have vastly different biogeochemical properties, including sorption, solubility,
      bioavailability, and toxicity. The use of high performance liquid chromatography
      (HPLC) coupled to elemental specific detectors, such as inductively coupled
      plasma mass spectrometry (ICP-MS), has become one of the most important
      speciation methods employed. This is due to the separation versatility of HPLC
      and the sensitive and selective detection capabilities of ICP-MS. The current
      study compares standard mode ICP-MS to recently developed reaction cell (RC) ICP
      MS, which has the ability to remove or reduce many common polyatomic
      interferences that can limit the ability of ICP-MS to quantitate certain analytes
      in complex matrices. Determination of chromium and selenium redox species is
      achieved using ion-exchange chromatography with elemental detection by standard
      and RC-ICP-MS, using various chromium and selenium isotopes. In this study,
      method performance and detection limits for the various permutations of the
      method (isotope monitored or ICP-MS detection mode) were found to be comparable
      and generally less than 1 microg L(-1). The method was tested on synthetic
      laboratory samples, surface water, groundwater, and municipal tap water matrices.

PMID- 19100880
TI  - Carrier element-free coprecipitation (CEFC) method for the separation,
      preconcentration and speciation of chromium using an isatin derivative.
AB  - A new, simple, rapid and sensitive separation, preconcentration and speciation
      procedure for chromium in environmental liquid and solid samples has been
      established. The present speciation procedure for Cr(III) and Cr(VI) is based on
      combination of carrier element-free coprecipitation (CEFC) and flame atomic
      absorption spectrometric (FAAS) determinations. In this method a newly
      synthesized organic coprecipitant, 5-chloro-3-[4-(trifluoromethoxy)
      phenylimino]indolin-2-one (CFMEPI), was used without adding any carrier element
      for coprecipitation of chromium(III). After reduction of chromium(VI) by
      concentrated H(2)SO(4) and ethanol, the procedure was applied for the
      determination of total chromium. Chromium(VI) was calculated as the difference
      between the amount of total chromium and chromium(III). The optimum conditions
      for coprecipitation and speciation processes were investigated on several
      commonly tested experimental parameters, such as pH of the solution, amount of
      coprecipitant, sample volume, etc. No considerable interference was observed from
      the other investigated anions and cations, which may be found in natural water
      samples. The preconcentration factor was found to be 40. The detection limit for
      chromium(III) corresponding to three times the standard deviation of the blank
      (N=10) was found 0.7 microg L(-1). The present procedure was successfully applied
      for speciation of chromium in several liquid and solid environmental samples. In
      order to support the accuracy of the method, the certified reference materials
      (CRM-TMDW-500 Drinking Water and CRM-SA-C Sandy Soil C) were analyzed, and
      standard APDC-MIBK liquid-liquid extraction method was performed. The results
      obtained were in good agreement with the certified values.

PMID- 19100881
TI  - Usefulness of parallel factor analysis to handle the matrix effect in the
      fluorescence determination of tetracycline in whey milk.
AB  - The determination of tetracycline by fluorescence spectrophotometry in complex
      matrices has some difficulties, because the presence of other compounds in the
      matrix affects the analytical signal. In this work, the effect of some inorganic
      species that are present in whey milk on the fluorescence signal of tetracycline
      is studied using a D-optimal experimental design. Next, an experimental strategy
      is proposed in conjunction with Parallel Factor Analysis, PARAFAC, modeling that
      leads to suitably modeling the severe matrix effect in the determination of
      tetracycline in whey milk. A specific design is performed in such a way that the
      lack of trilinearity due to the effect of the presence of interferents on the
      signal is obviated. Then, ten test samples from three brands of milk, spiked with
      different quantities of tetracycline and measured in 2 days were analysed using
      this methodology (mean of the absolute value of the relative errors: 5.1%). The
      developed analytical method fulfils the property of trueness, the relative errors
      being, both in calibration and prediction, inside the interval set by Commission
      Decision 2002/657/EC at these concentration levels. Decision limits (CCalpha) at
      x(0)=0 microg L(-1) and at x(0)=100 microg L(-1) were 13.2 and 112.4 microg L(-1)
      respectively, for alpha=0.05; whereas detection capabilities (CCbeta) were 25.9
      microg L(-1) and 124.4 microg L(-1) respectively for alpha=beta=0.05.

PMID- 19100882
TI  - Experimental monitoring and data analysis tools for protein folding: study of
      steady-state evolution and modeling of kinetic transients by multitechnique and
      multiexperiment data fusion.
AB  - Protein folding is a complex process that can take place through different
      pathways depending on the inducing agent and on the monitored time scale. This
      diversity of possibilities requires a good design of experiments and powerful
      data analysis tools that allow operating with multitechnique measurements and/or
      with diverse experiments related to different aspects of the process of interest.
      Multivariate curve resolution-alternating least squares (MCR-ALS) has been the
      core methodology used to perform multitechnique and/or multiexperiment data
      analysis. This algorithm allows for obtaining the process concentration profiles
      and pure spectra of all species involved in the protein folding from the sole raw
      spectroscopic measurements obtained during the experimental monitoring. The
      process profiles provide insight on the mechanism of the process studied whereas
      the shapes of the recovered pure spectra help in the characterization of the
      protein conformations involved. Relevant features of the MCR-ALS algorithm are
      the possibility to handle fused data, i.e., series of experiments monitored with
      different techniques and/or performed under different experimental conditions,
      and the flexibility to include a priori information linked to general properties
      of concentration profiles and spectra and to the kinetic model governing the
      folding process. All these characteristics help to obtain a comprehensive
      description of the protein folding mechanism. To our knowledge, this work
      includes for the first time the simultaneous analysis of steady-state and short
      time scale kinetic experiments linked to a protein folding process. The potential
      of this methodology is shown taking myoglobin as a model system for protein
      folding or, in general, for the study of any complex biological process that
      needs multitechnique and multiexperiment monitoring and analysis. Transformations
      in myoglobin due to changes in pH have been monitored by ultraviolet/visible (UV
      vis) absorption and circular dichroism (CD) spectroscopy. Steady-state and
      stopped-flow experiments were carried out to account for the evolution of the
      process at different time scales. In this example, the multiexperiment analysis
      has allowed for the reliable detection and modeling of a kinetic transient
      species in the myoglobin folding process, absent in the steady-state working
      conditions.

PMID- 19100883
TI  - Dendrimer-rhodium nanoparticle modified glassy carbon electrode for amperometric
      detection of hydrogen peroxide.
AB  - Metallic nanoparticles of rhodium were prepared by using the newly synthesized
      N,N-bis-succinamide-based dendrimer as stabilizers. The Rh nanoparticles were
      spherical shaped with a particle size of approximately 2 nm. The dendrimer Rh
      encapsulated nanoparticles (Rh-DENs) were immobilized on glassy carbon electrode
      (GCE) and their electrocatalytic activity towards hydrogen peroxide reduction was
      investigated using cyclic voltammetry and chronoamperometry. The Rh-DENs modified
      GCE showed excellent electrocatalytic activity for hydrogen peroxide reduction
      reactions. The steady-state cathodic current response of the modified electrode
      at -0.3 V (vs SCE) in phosphate buffer (pH 7.0) showed a linear response to
      hydrogen peroxide concentration ranging from 8 to 30 microM with a detection
      limit and sensitivity of 5 microM and 0.03103x10(-6) A microM(-1), respectively.

PMID- 19100884
TI  - pH(stat) vs. single extraction tests to evaluate heavy metals and arsenic
      leachability in environmental samples.
AB  - Here we compared the pH(stat) test, which examines the leachability of major
      elements (Ca, Mg, Al, Fe, and Mn), dissolved organic carbon, and trace elements
      (Cd, Zn, Cu, Pb, and As) in a wide pH range, with single extraction tests based
      on the use of mild extractants (calcium chloride, acetic acid or EDTA). For this
      purpose, we examined samples from a variety of environmental conditions (sludges,
      mineral soils, organic soils, and soils with particulate and/or soluble
      contamination). Extraction yields obtained with CaCl(2) (0.01 mol L(-1)) and
      CH(3)COOH (0.43 mol L(-1)) correlated well with those from the pH(stat) at the
      same pH (r=0.98 and 0.95, respectively), while the use of EDTA (0.05 mol L(-1))
      led to systematically higher extraction yields than those quantified with the
      pH(stat) at the same pH. However, the pH(stat) test had three distinct
      advantages: (1) it revealed the relationship between the solubility of the main
      soil phases and pH; (2) it showed the variation in pollutant leachability due to
      changes in pH; and (3) it better predicted the maximum contaminant availability.
      Thus we propose that the pH(stat) is the best laboratory tests to evaluate the
      contaminant leachability over a wide range of sample types (soil, sludge, and
      sediment).

PMID- 19100885
TI  - Dispersive liquid-liquid microextraction followed by high-performance liquid
      chromatography as an efficient and sensitive technique for simultaneous
      determination of chloramphenicol and thiamphenicol in honey.
AB  - Dispersive liquid-liquid microextraction (DLLME) coupled with high-performance
      liquid chromatography-variable wavelength detector (HPLC-VWD) was developed for
      extraction and determination of chloramphenicol (CAP) and thiamphenicol (THA) in
      honey. In this extraction method, 1.0 mL of acetonitrile (as dispersive solvent)
      containing 30 microL 1,1,2,2-tetrachloroethane (as extraction solution) was
      rapidly injected by syringe into a 5.00-mL water sample containing the analytes,
      thereby forming a cloudy solution. After extraction, phase separation was
      performed by centrifugation and the enriched analytes in the sedimented phase
      were determined by HPLC-VWD. Some important parameters, such as the nature and
      volume of extraction solvent and dispersive solvent, extraction time, sample
      solution pH, sample volume and salt effect were investigated and optimized. Under
      the optimum extraction condition, the method yields a linear calibration curve in
      the concentration range from 3 to 2000 microg kg(-1) for target analytes. The
      enrichment factors for CAP and THA were 68.2 and 87.9, and the limits of
      detection (S/N=3) were 0.6 and 0.1 microg kg(-1), respectively. The relative
      standard deviations (RSDs) for the extraction of 10 microg kg(-1) of CAP and THA
      were 4.3% and 6.2% (n=6). The main advantages of DLLME-HPLC method are simplicity
      of operation, rapidity, low cost, high enrichment factor, high recovery, good
      repeatability and extraction solvent volume at microliter level. Honey samples
      were successfully analyzed using the proposed method.

PMID- 19100886
TI  - Influence of temperature on mass transfer in an incomplete trapping single hollow
      fibre supported liquid membrane extraction of triazole fungicides.
AB  - The influence of temperature in a single hollow fibre supported liquid membrane
      extraction of triazole fungicides with a stagnant acceptor phase was
      investigated. The mass transfer parameters such as diffusion coefficient, flux
      and apparent viscosity were determined at temperature ranging from 278 K to 313
      K. Increase in temperature led to an increase in diffusion coefficient and flux.
      The apparent viscosity also decreased with an increase in temperature. The degree
      of trapping in the acceptor phase influenced the mass transfer at higher
      temperature. At lower temperature, the transport of analytes from the donor
      solution through the donor-membrane interface and through the membrane mainly
      affected the transport of triazole fungicides. The effect of temperature in a
      single hollow fibre SLM extraction technique is therefore more pronounced where
      transport is donor controlled and/or membrane controlled. The partition
      coefficient of analytes from the acceptor solution to the membrane, K(A) was
      found to be much higher than that of from the donor solution to the membrane
      K(D), thus least trapped triazole fungicides preferred to remain in the membrane
      even with an increased extraction temperature.

PMID- 19100887
TI  - Selective determination of cyanides by gas diffusion-stopped flow-sequential
      injection analysis and an on-line standard addition approach.
AB  - A highly selective sequential injection (SI) method for the automated
      determination of weak-acid-dissociable cyanides is reported. The analytical
      procedure is based on the on-line reaction of the analyte with ninhydrin in
      carbonate medium to form a coloured product (lambda(max)=510 nm). Cyanides are
      removed from sample matrix by acidification through a gas-diffusion step
      incorporated in the SI manifold. The effect of instrumental and chemical
      variables was studied. By adopting an on-line standard addition protocol, the
      sensitivity of the proposed method was enhanced drastically, without affecting
      the determination range. The assay was validated in terms of linearity (up to 200
      microg L(-1)), limit of detection (c(L)=2.5 microg L(-1)), limit of quantitation
      (c(Q)=7.5 microg L(-1)), precision (s(r)<2.5% at 100 microg L(-1)) and
      selectivity. High tolerance against critical species such as sulfides and
      thiocyanates was achieved. The applicability of the method was demonstrated by
      analyzing tap and mineral water samples at levels below the limits established by
      international E.U. and U.S. organizations. The percent recoveries were
      satisfactory in all cases, ranging between 94.2 and 103.6%.

PMID- 19100888
TI  - Quantitative metabolic profiling of 21 endogenous corticosteroids in urine by
      liquid chromatography-triple quadrupole-mass spectrometry.
AB  - Since corticosteroid metabolism may be affected by disease states, the accurate
      and precise measurement of endogenous corticosteroids in urine is necessary to
      understand their biochemical roles. An efficient quantitative profiling of 21
      endogenous corticosteroids in urine has been validated by liquid chromatography
      tandem mass spectrometry (LC-MS/MS). After enzymatic hydrolysis with beta
      glucuronidase, samples were purified using a solid-phase extraction cartridge and
      then separated through a sub-2 microm particle C18 column (2.1 mm x 50 mm, 1.9
      microm) and quantified within 12.1 min using a triple quadrupole MS with
      electrospray ionization in positive ion mode. All corticosteroids resulted in the
      base-line separation, which is even achieved for stereo-isomers, such as alpha
      /beta-cortol, alpha-/beta-cortolone, and allo
      tetrahydrocortisol/tetrahydrocortisol. Overall recoveries ranged from 85% to 106%
      with limit of quantification ranged from 0.5 to 2.0 ng mL(-1) for the
      corticosteroids examined. The precision (% CV) and accuracy (% bias) of the assay
      were 1.7-7.8% and 95.1-105.4%, respectively, in 0.5-200 ng mL(-1) calibration
      ranges (r(2)>0.9903), for quality-control samples containing 21 endogenous
      corticosteroids at three different urinary concentrations. Clinical application
      included quantitative analysis from patients with both prostate cancer and benign
      prostatic hyperplasia with altered cortisol concentrations. The described LC
      MS/MS method eliminates interference from other urine components, has excellent
      chromatographic resolution achieved by a small particle LC column with a
      sufficient sensitivity to allow the profiling of both gluco- and mineralo
      corticosteroids at a time.

PMID- 19100889
TI  - Stopped-flow kinetic method for the fluorimetric determination of DNA traces in
      biological samples based on the interaction long-wavelength fluorophor,
      surfactant and nucleic acid.
AB  - A simple and rapid method for the determination of DNA, involving the interaction
      between a surfactant, a long-wavelength fluorophor (LWF) and the nucleic acid, is
      presented. Different chemical systems based on the local effective charge of the
      surfactant/LWF system with DNA were tested, choosing cetyltrimethyl ammonium
      bromide (CTAB) and indocyanine green (ICG) for the development of the method. The
      fluorescence of ICG increases in the presence of CTAB, but it rapidly decreases
      in the presence of deoxyribonucleic acid. The initial reaction-rate (v(0)) and
      signal at a prefixed-time (DeltaIF(20)) are monitored at 780 and 802 nm as
      excitation and emission wavelengths, respectively, using stopped-flow mixing
      technique, which makes the method applicable to automate routine analysis. Each
      measurement was obtained in about 30 s, being the integration time 0.1 s. The
      dynamic range of the calibration graph was 10-1500 ng mL(-1), with a detection
      limit of 5 ng mL(-1). The precision of the method, expressed as relative standard
      deviation, ranged between 2.1% and 4.5%. After a sample treatment consisting on a
      conventional extraction, the method was applied to the determination of DNA in
      several samples from different biological materials.

PMID- 19100890
TI  - Resonance Rayleigh scattering spectra of ion-association nanoparticles of [Co(4
      [(5-chloro-2-pyridyl) azo]-1, 3-diaminobenzene)2]2+-sodium dodecyl benzene
      sulfonate system and its analytical application.
AB  - In pH 1.8-3.0 Britton-Robinson (BR) buffer solution, cobalt (II) reacts with 4
      [(5-Chloro-2-pyridyl) azo]-1, 3-diaminobenzene (5-Cl-PADAB, L) to form a cationic
      chelate [CoL(2)](2+). When interacting with anionic surfactants (AS) such as
      sodium dodecyl benzene sulfonate (SDBS), sodium dodecyl sulfate (SDS) or sodium
      dodecyl sulfonate (SLS), the chelate can only react with SDBS to form ternary ion
      association complexes ([CoL(2)][SDBS](2)). By virtue of the extrusion action of
      water and Van der Waals force, the hydrophobic ion-association complexes draw
      close to each other and further aggregate to form {[CoL(2)][SDBS](2)}(n)
      nanoparticles with an average diameter of 30 nm. As a result, resonance Rayleigh
      scattering (RRS) is enhanced greatly and new RRS spectra appear. Under the same
      conditions, both SDS and SLS exhibit no similar reactions and do not result in
      obvious change of RRS. Therefore, SDBS can be determined selectively by RRS
      method in the presence of SDS or SLS. The wavelength of 516 nm was chosen as a
      detection wavelength, the linear range and the detection limit (3sigma) are 0.05
      6.0 microg mL(-1) and 0.015 microg mL(-1) for the determination of SDBS,
      respectively. The characteristics of RRS spectra of the [CoL(2)](2+)-SDBS system,
      the optimum conditions of the reaction and the influencing factors have been
      investigated. The effects of coexisting substances have been examined too,
      indicating a good selectivity of the method for the determination of SDBS. The
      method can be used for the determination of SDBS in waste water and river water
      samples, and the results are satisfactory compared with those of standard samples
      of SDBS. Based on the formation of {[CoL(2)][SDBS](2)}(n) nanoparticles, a
      sensitive, simple and rapid method has been developed for the determination of
      SDBS in environmental water samples using a RRS technique. Moreover, the reaction
      mechanism was discussed.

PMID- 19100891
TI  - Comparison of near-infrared and Raman spectroscopy for the determination of the
      density of polyethylene pellets.
AB  - In this study, we compare near-infrared (NIR) and Raman spectroscopy for the
      determination of the density of linear low density polyethylene (PE) (in a pellet
      form). As generally known, Raman spectral features are more selective than those
      of NIR for most chemical samples. NIR spectroscopy has been more extensively used
      for the quantitative analysis of polymers, but Raman spectroscopy is the better
      choice as long as the problem of reproducibility of Raman measurements
      (especially for solid samples), mostly resulting from insufficient sample
      representation due to probing only localized chemical information and the
      sensitivity of sample placement with regard to the focal plane, can be overcome.
      To improve sample representation and reproducibility of Raman measurements, we
      have employed the wide area illumination (WAI) Raman scheme, capable of
      illuminating a laser onto a large sample area (28.3 mm(2)) for Raman spectral
      collection (a 6-mm laser spot with a focal length of 248 mm). Diffuse reflectance
      NIR spectra of PE pellets were collected using a sample moving system which
      allowed for the scanning of large areas. The prediction error was 0.0008 g cm(-3)
      for Raman spectroscopy and 0.0011 g cm(-3) for NIR spectroscopy. The
      harmonization of inherently selective Raman features and a reproducible spectral
      collection with correct sample representations using the WAI scheme led to an
      accurate determination of the density of the PE pellets.

PMID- 19100892
TI  - Simultaneous detection for three kinds of veterinary drugs: chloramphenicol,
      clenbuterol and 17-beta-estradiol by high-throughput suspension array technology.
AB  - Suspension array technology for simultaneous detection of three kinds of
      veterinary drugs, chloramphenicol (CAP), clenbuterol and 17-beta-estradiol has
      been developed. Conjugates of chloramphenicol and clenbuterol coupled with bovine
      serum albumin were synthesized and purified. Probes of suspension array were
      constituted by coupling the three conjugates on the fluorescent
      microspheres/beads and the microstructures of the beads' surface were observed by
      scanning electron microscopy which was a direct confirmation for the successful
      conjugates' coupling. The optimal addition of conjugates and the amounts of
      antibodies were optimized and selected, respectively. Standard curves were
      plotted and the coefficient of determination-R(2) was greater than 0.989 which
      suggested good logistic correlation. The detection ranges for the three
      veterinary drugs are 40-6.25x10(5) ng L(-1), 50-7.81x10(5) ng L(-1) and 1x10(3
      )7.29x10(5) ng L(-1), respectively and the lowest detection limits (LDLs) of them
      are 40, 50 and 1000 ng L(-1), respectively. The suspension array is specific and
      has no significant cross-reactivity with other chemicals. Meanwhile, unknown
      samples were detected by suspension array and ELISA in comparison with each
      other. The errors between found and real for the detection of the unknown samples
      were relatively small to both of the two methods, whereas, the detection ranges
      of suspension array are broader and sensitive than that of the traditional ELISA.
      The high-throughput suspension array is proved to be a novel method for multi
      analysis of veterinary drugs with simple operation, high sensitivity and low
      cost.

PMID- 19100893
TI  - Inkjet-printed gold nanoparticle chemiresistors: influence of film morphology and
      ionic strength on the detection of organics dissolved in aqueous solution.
AB  - The influence of film morphology on the performance of inkjet-printed gold
      nanoparticle chemiresistors has been investigated. Nanoparticles deposited from a
      single-solvent system resulted in a "coffee ring"-like structure with most of the
      materials deposited at the edge. It was shown that the uniformity of the film
      could be improved if the nanoparticles were deposited from a mixture of solvents
      comprising N-methyl-2-pyrrolidone and water. Electrical conductivity measurements
      showed that both "coffee ring" and "flat" films were qualitatively similar
      suggesting that the films have similar nanoscale structures. To form the
      functional chemiresistor device, the 4-(dimethylamino)pyridine coating on the
      nanoparticle was exchanged with 1-hexanethiol to provide a hydrophobic sensing
      layer. The performance of 1-hexanethiol coated gold nanoparticle chemiresistors
      to small organic molecules, toluene, dichloromethane and ethanol dissolved in 1 M
      KCl in regard to changes in impedance and response times was unaffected by the
      film morphology. For larger hydrocarbons such as octane, the rate of uptake of
      the analyte into the film was significantly faster when the flatter nanoparticle
      film was used as opposed to the "coffee ring" film which has a thicker edge.
      Furthermore, the presence of potassium and chloride ions in the solution media
      does not significantly affect the impedance of the nanoparticle film at 1 Hz (<2%
      variation in film impedance over more than four orders of magnitude change in
      ionic strength). However, the ionic strength of the media affected the
      partitioning of the analyte into the hydrophobic nanoparticle film. The response
      of the sensor was found to increase with an increased salt concentration due to a
      salting-out of the analyte from the solution.

PMID- 19100894
TI  - Towards integrated devices for computer screen photo-assisted multi-parameter
      sensing.
AB  - The computer screen photo-assisted technique (CSPT) utilizes consumer electronic
      devices such as computer screens and web cameras for distributed chemical
      sensing. Key to this method is the development of small and disposable sensing
      assays able to aid the CSPT optical detection, and the evaluation of multiple
      indicators. Here we demonstrate CSPT identification of fluorescent indicators
      from individual 100 microm SU-8 (10) pillars covering an area of 4 mm x 4 mm with
      a density of 47 elements mm(-2). The extraction of distinctive spectral
      fingerprints is aided by the exploitation of a three-band Moire interference that
      enables the partial Bayer decoding of the CSPT images.

PMID- 19100895
TI  - Sample stacking for determination of aromatic acid impurities by microemulsion
      electrokinetic chromatography.
AB  - In this study, a sample stacking step coupled with microemulsion electrokinetic
      chromatography (MEEKC) was used to detect and analyze nine aromatic acids
      (benzoic acid (BA), isophthalic acid (IPA), terephthalic acid (TPA), p-toluic
      acid (p-TA), 4-carboxylbenzaldehyde (4-CBA), trimesic acid (TSA), trimellitic
      acid (TMA), o-phthalic acid (OPA), and hemimellitic acid (HMA)) which are common
      impurities produced during aromatic acid synthesis. First, the presence of both
      acid and water plugs at the front of the capillary improved the reproducibility
      in retention time and peak intensity of the tested analytes in the stacking
      method. Second, the pH and the electrolyte type of acidic plug and sample matrix
      were found to be the predominant influences on the aromatic acid stacking. The
      detection limits of these aromatic acids were reduced to the range of 0.00007
      0.00032 microg mL(-1) by this optimal sample stacking step. This proposed on-line
      concentration MEEKC method was able to detect trace levels of aromatic acid
      impurities in commercial aromatic acid products that were not previously possible
      by the normal MEEKC method. Furthermore, these results in comparison with our
      previous studies on sample stacking MEEKC method indicated that all acidic
      species were concentrated by this simple stacking procedure. The sensitivity
      enhancement, however, was highly dependent on the types of functional groups
      present in the structures of analytes, and the enhancement was in the order of
      first the compounds carrying both carboxy and hydroxy groups (e.g. phenolic
      acid), followed by carboxylic acid compounds (e.g. aromatic acid), and then
      phenol compounds (e.g. polyphenol).

PMID- 19100896
TI  - Evaluation of a Microbiological Multi-Residue System on the detection of
      antibacterial substances in ewe milk.
AB  - To protect both, public health and the dairy industry, from the presence of
      antibiotic residues in milk, control programmes have been established, which
      include the needed screening tests. This work focuses on the application of a
      Microbiological Multi-Residue System in ewe milk, a method based on the use of
      six different plates, each seeded with one of the following bacteria: Geobacillus
      stearothermophilus var. calidolactis (beta-lactams), Bacillus subtilis at pH 8.0
      (aminoglycosides), Kocuria rhizophila (macrolides), Escherichia coli
      (quinolones), B. cereus (tetracyclines) and B. subtilis at pH 7.0
      (sulphonamides), respectively. Twenty-three antimicrobial substances were
      analysed and a logistic regression was established for each substance assayed to
      relate the antibiotic concentration and the zone of microbial growth inhibition.
      Great linearity in the response was observed (regression coefficients of over
      0.97). This fact suggests the possibility of establishing a decision level of
      antibiotic concentrations near to the Maximum Residue Limits (MRL). Zones of
      inhibition were suggested as proposed action levels for the different
      antimicrobial groups (diameters of inhibition of 18 mm for the aminoglycoside,
      beta-lactam and sulphonamide plates; 19 mm for the tetracycline plate, 21 mm for
      the macrolide plate, and 24 mm for the quinolone plate). Specificity and cross
      reactivity were also assayed.

PMID- 19100898
TI  - T-regulatory cells-what relationship with immunosuppressive agents?
AB  - The immune system maintains self-tolerance through the interplay of several
      mechanisms. One of the key mechanisms is the suppression of effector cells
      through regulatory T cells (Tregs). Recent progress has allowed the
      identification, analysis, and experimental manipulation of various subpopulations
      of Tregs. Several major issues regarding Tregs have emerged in relation to organ
      transplantation, including the questions of whether immunosuppressive drugs
      influence Tregs and whether Tregs can be used therapeutically to achieve graft
      acceptance or even tolerance. Although none of the available immunosuppressive
      drugs have been specifically designed to influence Tregs, they nevertheless do so
      through various pathways. Notably, current evidence suggests that rapamycin has a
      favorable effect on Tregs in organ transplant recipients, whereas calcineurin
      inhibitors (CNI) have markedly negative effects on Tregs. The idea of inducing
      tolerance through the therapeutic administration of Tregs has received much
      attention in recent years. To obtain sufficient numbers of recipient-derived
      Tregs, various strategies are being investigated to expand sorted Treg
      populations. Rapamycin has been found to significantly promote the in vitro
      expansion of murine and human Tregs; it may thereby help to generate clinically
      relevant quantities of Tregs. However, no data have yet been published that would
      demonstrate that the therapeutic use of Tregs induces transplantation tolerance
      across full major histocompatibility complex barriers in immunocompetent mice
      displaying a polyclonal T-cell repertoire.

PMID- 19100899
TI  - Fifteen years of clinical studies and clinical practice in renal transplantation:
      reviewing outcomes with de novo use of sirolimus in combination with
      cyclosporine.
AB  - Over the course of 15 years the use of sirolimus, a macrocyclic lactone, has
      evolved from an adjunct to calcineurin inhibitors (CNI) to the foundation of
      therapy due to the drug's unique properties: First, it displays synergistic
      pharmacodynamic interactions with CNI. Even among high immunologic risk patients,
      this regimen attenuates the risk of acute allograft rejection episodes when used
      in combination with cyclosporine or tacrolimus. Indeed >80% reduction in CNI
      exposure de novo yields better long-term renal function than full cyclosporine
      (CsA) doses, a useful tradeoff, despite the augmented occurrence of lymphoceles
      and impaired wound healing. Second, by inhibiting mammalian target of rapamycin
      (mTOR), it exerts profound anti-neoplastic effects reducing the incidence and
      mediating the regression of tumors displaying PTEN-deletions and/or Akt
      activations in transplant and non-transplant patients. Third, it is relatively
      non-nephrotoxic although it may exacerbate that property of CNI agents. Fourth,
      it allows prompt withdrawal of steroid therapy. Fifth, it displays reduced rates
      of cytomegalovirus, and BK virus infections. The major adverse reactions can
      generally be controlled with countermeasure therapy. Myelosuppressive effects,
      which tend to be transient (unless sirolimus is combined with mycophenolic acid),
      are readily amenable to treatment with granulocyte colony stimulating factor for
      leukopenia, interleukin 11 for thrombocytopenia and erythropoietin for anemia.
      Combinations of statins and fibrates represent effective countermeasure therapy
      for hypercholesterolemia and hypertriglyceridemia, respectively. Idiosyncratic
      reactions include hypoxemic pulmonary toxicity, refractory edema and diarrhea.
      Thus, sirolimus represents the vanguard of a new class of maintenance agents for
      immunosuppression.

PMID- 19100900
TI  - Addressing the challenges for improving long-term outcomes in renal
      transplantation.
AB  - Renal transplant patients lose their grafts most frequently from chronic
      allograft nephropathy and their lives from cardiac disease, malignancy, and
      infection. These are thus the challenges for renal transplant programs for this
      decade, just as acute rejection was the challenge of the last two decades. Most
      immunosuppressive protocols aim to minimize acute allograft rejection through
      heavy induction strategies and powerful but toxic maintenance therapies,
      counterbalanced by powerful and expensive infection prophylaxis. However, while
      the short-term results have improved steadily from the 1980s, and despite all the
      current efforts, the long-term success rates of renal transplants have not
      improved. Future aims include controlling both rejection and the long-term
      consequences of toxicity and infection risk. The biological facts that have
      determined our approach to the use of immunosuppressants have required us to try
      to balance the conflicting need for control of the allograft response and the
      inevitable toxicities of our drugs. The early period after transplantation
      requires maximum immunosuppressive efficacy with minimal ischemia reperfusion and
      good surgical-related wound healing. The latter period after transplantation
      requires less immunosuppressive efficacy and avoidance of chronic nephrotoxicity,
      cardiovascular, and malignancy risk factors. This usually leads to an induction
      strategy using a biological agent; a calcineurin inhibitor; an antiproliferative
      agent; and variable use of corticosteroids. In the long term, there are a variety
      of strategies for dose reduction or elimination of calcineurin inhibitors,
      incorporation of mammalian target of rapamycin inhibitors, and variable
      approaches to the risks of continued low-dose corticosteroids. The multiplicity
      of alternative strategies available testifies to the absence of evidence for a
      single dominant protocol and the urgent need to determine the relevant early
      indicators for measuring long-term success.

PMID- 19100901
TI  - Modern approaches to combining sirolimus with calcineurin inhibitors.
AB  - Routine renal transplantation maintenance immunosuppression at the University of
      Nebraska Medical Center consists of rabbit anti-thymocyte globulin (rATG)
      induction with early steroid withdrawal followed by maintenance with sirolimus
      and tacrolimus, a regimen we have used with >900 patients. Induction consists of
      6 mg/kg rATG in 4 doses of 1.5 mg/kg each on days 0, 2, 4, and 6. Prednisone is
      used only in association with rATG administration. Maintenance agents are
      introduced gradually depending on renal function. Since April 2004, we have been
      conducting a prospective, randomized trial of this regimen versus 2
      modifications: administering the rATG induction dose (6 mg/kg) in a single
      infusion over 24 hours; and, after 6 months, replacing tacrolimus with
      mycophenolate mofetil (MMF) in half of the study subjects. This study has shown
      several benefits of single-dose rATG induction, including significantly improved
      early graft function with both living and deceased donor kidneys and improved 2-
      to 12-month function in deceased donor organs (P = .026). Single-dose lymphocyte
      counts return to baseline sooner (2.2 vs 15.3 years; P < .05) without increased
      rejection (1 year; 8.5% single vs 12.5% divided; P = NS), and single-dose
      induction reduces chronic allograft nephropathy at 1 year (P = .05). Preliminary
      results of replacing tacrolimus with MMF show immediately improved renal function
      (months 1 and 2; P = .02 and .05; months 1-6, P = .058) without increased
      rejection.

PMID- 19100902
TI  - Reviewing the evidence for de novo immunosuppression with sirolimus.
AB  - Calcineurin inhibitors (CNIs), introduced in the 1980s, have been the foundation
      of maintenance immunosuppression in solid organ transplantation because they
      substantially reduce the risk of acute rejection and improve short-term outcomes.
      However, CNIs (both tacrolimus and cyclosporine) are implicated in direct and
      indirect nephrotoxicity, leading to tubular atrophy, interstitial fibrosis, and
      glomerulosclerosis. Therefore, CNI reduction or minimization has been a
      longstanding goal, and reducing CNI drug doses at virtually any time
      posttransplantation will improve glomerular filtration rate (GFR) by 10%-20%. One
      approach to avoid these long-term changes is to use a CNI-free regimen for
      maintenance therapy based on sirolimus, which has a different mechanism of
      action. The use of a de novo regimen including an induction antibody followed by
      sirolimus, mycophenolate mofetil, and steroids has been used in several trials
      (>1000 patients), consistently demonstrating improved renal function at 1, 2, and
      now 5 years. Long-term analysis has confirmed significantly improved renal
      function (creatinine and estimated and measured GFR), preservation of kidney
      histology, and death censored graft survival compared with CNI-based regimens.
      This combination has a somewhat different side effect profile, and wider
      experience has revealed that the use of de novo sirolimus requires careful
      therapeutic drug level monitoring to optimize these results. In addition, the de
      novo introduction of sirolimus should be restricted in the obese, in the presence
      of dense oligoanuria, and among subjects at high immunologic risk for an acute
      rejection episode.

PMID- 19100903
TI  - Optimizing early de novo immunosuppression with sirolimus.
AB  - In the past, renal transplant deterioration was approached as a problem of
      "chronic rejection," which implied that deterioration of kidney function occurred
      because of past injuries that programmed the kidney for loss of function. New
      evidence suggests that deterioration occurs because of a new or recent source of
      injury. If a graft is losing function, the cause of deterioration needs to be
      identified. Some causes are treatable; those that are not should be diagnosed and
      further studied. To this end, we need to approach deterioration (loss of function
      or proteinuria) of renal transplant function by identifying distinct entities or
      components of the problem. Early and late kidney graft survival has improved
      considerably, owing to advances in clinical care, particularly immunosuppression.
      Many of the kidney transplants functioning today should serve their new owners
      for their life expectancy. The main cause of late kidney function deterioration
      remains allograft nephropathy. Often this reflects a failure of the
      immunosuppressive prescription. Subclinical rejection, chronic nephrotoxicity,
      recurrent disease, infections, or diabetes may contribute to this process.
      Optimal early and late immunosuppression is required to provide efficacy without
      attendant risk for graft dysfunction owing to nephrotoxicity. Because 1-year
      serum creatinine levels often provide an indication of long-term graft function,
      early evaluation of subtle degrees of graft dysfunction should prompt a graft
      biopsy to identify treatable causes.

PMID- 19100904
TI  - The impact of mTOR inhibitors on the development of malignancy.
AB  - Although continuous improvements have been made in fighting rejection with
      immunosuppressive drugs in transplant recipients, this success story has been
      tempered by an associated high incidence of cancer. The latest projections are
      that cancer might exceed cardiovascular disease as the leading cause of death
      among transplant recipients. Indeed, immunosuppression reduces our natural
      ability to destroy cancer cells and to inhibit viral infections potentially
      linked to cancer development. Therefore, a strategy to counter the problem of
      cancer in transplantation is needed. Recently, mammalian target of rapamycin
      (mTOR) inhibitors have demonstrated potential as both immunosuppressive and
      anticancer agents. Although mTOR inhibitors prevent organ transplant rejection,
      this class of drugs has potential anticancer properties that may be useful in the
      "balance of effects" toward cancer-free survival in transplant recipients.
      Mechanisms of mTOR inhibitors' anticancer effects are multiple, affecting
      processes including angiogenesis, cell proliferation, cell survival, and
      molecular oncogenic signaling. Importantly, experimental work supports the view
      that tumor inhibition can be accomplished with mTOR inhibitors while protecting
      allografts against rejection. Most recently, prospective randomized clinical
      studies have been initiated to test the concept that mTOR inhibitors reduce
      cancer while simultaneously inhibiting allograft rejection. One such study, the
      SiLVER trial, examines hepatocellular carcinoma recurrence in mTOR inhibitor
      treated liver transplant patients. More robust evidence as to whether cancer risk
      can be reduced in transplant recipients with mTOR inhibitors may come from such
      clinical trials.

PMID- 19100905
TI  - Temsirolimus in renal cell carcinoma.
AB  - Patients with metastatic renal cell carcinoma (RCC) generally show a poor
      prognosis; treatment approaches have not significantly improved patient survival.
      Temsirolimus inhibits the mammalian target of rapamycin kinase. Clinical studies
      have shown positive results when the drug is administered to patients with this
      disease. The clinical benefit of temsirolimus for poor-risk, advanced RCC
      patients was demonstrated in a Phase III study comparing temsirolimus with
      interferon alpha (IFN-alpha) or combined temsirolimus plus IFN-alpha as first
      line treatment of advanced RCC, showed that treatment with temsirolimus alone
      significantly increased median overall survival in poor-risk, advanced RCC
      patients (10.9 vs 7.3 vs 8.4 months). This was the first Phase III trial to
      demonstrate an overall improvement in survival using an agent as "targeted
      therapy" for patients with advanced RCC. By November 2007, 200 patients with
      advanced RCC had been treated with temsirolimus before its approval by the
      European Medicines Agency (EMEA) within a compassionate use program. The single
      center treatment experiences using temsirolimus in patients for compassionate use
      are described herein. The treatment was generally well tolerated; side effects
      (mucositis, diabetes, and peripheral edema) were within the range expected from
      the pivotal trials and manageable with supportive care. Further development
      strategies for temsirolimus in patients with RCC include its evaluation with
      bevacizumab and also as second-line therapy in patients who have failed first
      line therapy with sunitinib.

PMID- 19100906
TI  - Minimizing the risk of posttransplant malignancy.
AB  - Recent improvements in immunosuppressive therapies have reduced the incidence of
      acute rejection and increased patient survival. These agents may however
      contribute to higher rates of mortality due to an increased risk of
      cardiovascular disease or malignancy. Transplant patients are immunocompromised
      with a reduced ability to combat the development of malignancy. The higher risk
      for the activity of oncoviruses may also contribute to the higher incidence and
      determine specific tumor types. Some immunosuppressants seem to have direct
      oncogenic effects. In vitro data have demonstrated that calcineurin inhibitors
      (CNIs) may show direct effects on tumor growth and the development of metastases.
      In contrast, mTOR inhibitors have demonstrated anti-tumoral properties in vitro
      and perhaps potent anti-angiogenic effects thereby. Recent studies and registry
      analyses have confirmed that mTOR inhibitors are associated with a reduced
      incidence of malignancies. UNOS data demonstrated that an mTOR inhibitor, with or
      without a CNI, is associated with a reduced incidence of tumors compared to
      regimens without mTOR inhibitors. The Rapamune Maintenance Regimen study
      demonstrated that patients receiving sirolimus-based, CNI-free therapy after CsA
      withdrawal at 3 months showed a reduced incidence of malignancy at 5 years
      posttransplant, compared with those who continued on a regimen that included CsA.
      In the CONVERT study, patients converted to sirolimus revealed a significantly
      lower malignancy rate at 24 months (3.1%) compared with those who continued CNI
      based therapy (9.8%, P < .001). The elimination of CNIs and the introduction of
      sirolimus may, therefore, have a role to reduce the risk of cancer among
      posttransplant patients.

PMID- 19100907
TI  - Biomarkers-a potential route for improved diagnosis and management of ongoing
      renal damage.
AB  - Currently, the identification and validation of biomarkers of kidney injury is
      among the top priorities of many diagnostic biotechnology companies as well as
      academic research institutes. Specifically, in renal transplantation, validated
      biomarkers of tissue injury with good discriminatory power between the various
      renal compartments and the underlying pathophysiology are desired, because
      sequential allograft biopsies are limited in number and cannot be used as a
      screening tool. Given the high demands on these markers, it is not surprising
      that none of those currently under evaluation has been thoroughly validated for a
      specific entity. Published biomarker candidates for early tubular damage include
      neutrophil gelatinase-associated lipocalin (NGAL), interleukin (IL)-18, soluble
      CD30, perforin, and granzyme B. Recently, C4d flow panel reactive antibodies were
      evaluated as biomarkers for humoral alloimmune responses. Additional biomarkers
      such as FOXP3 and kidney injury molecule 1 have been studied in the maintenance
      phase of renal transplantation. Given the complex prerequisites, it is not
      surprising that no biomarker panel has been sufficiently validated for clinical
      use. However, in the near future a biomarker for use as an indicator of renal
      tubule cell injury will be available. Troponin T or transaminase of the kidney
      may then at least be used to differentiate between functional renal failure
      (equivalent to a rise in creatinine) and intrinsic kidney injury.

PMID- 19100908
TI  - Reducing the risk of viral infection in renal transplantation.
AB  - Viruses are under constant surveillance by the immune system. With the
      introduction of more potent immunosuppressive regimens in transplantation, the
      increased risk of infectious diseases accompanies the decreased risk of acute
      rejection. Is the overall burden of immunosuppression the prime consideration or
      do the various immunosuppressive agents contribute individual risks? Do some
      immunosuppressive agents actually protect against viral disease? Cytomegalovirus
      (CMV) was initially a significant complication of transplantation, but the
      incidence of severe CMV disease has decreased with the identification of high
      risk groups and the introduction of screening and prophylactic strategies to
      control reactivation and de novo infection. Antiviral agents with specificity
      against CMV have been developed; however, CMV has developed resistance to
      antiviral agents, causing concern. BK polyomavirus is an emerging threat to renal
      transplantation, as BK nephropathy can cause significant graft loss, often within
      the first few years of the transplant. Return to dialysis carries increased
      morbidity and mortality and reduced quality of life. This brief overview examines
      the clinical literature regarding these viruses and discusses the potential for
      manipulating intracellular signaling pathways using specific immunosuppressive
      agents to inhibit viral reactivation and replication.

PMID- 19100909
TI  - mTOR-what does it do?
AB  - Target of rapamycin (TOR) is a highly conserved serine/threonine kinase that
      controls cell growth and metabolism in response to nutrients, growth factors,
      cellular energy, and stress. TOR, which was originally discovered in yeast, is
      conserved in all eukaryotes including plants, worms, flies, and mammals. The
      discovery of TOR led to a fundamental change in how we think about cell growth.
      It is not a spontaneous process that just happens when building blocks
      (nutrients) are available, but rather a highly regulated, plastic process
      controlled by TOR-dependent signaling pathways. TOR is found in 2 structurally
      and functionally distinct multiprotein complexes, TORC1 and TORC2. The 2 TOR
      complexes, like TOR itself, are highly conserved. Mammalian TORC1 (mTORC1) is
      rapamycin sensitive and contains mTOR, raptor, and mLST8. TORC1 in yeast and
      mammals mediates temporal control of cell growth by regulating several cellular
      processes, including translation, transcription, ribosome biogenesis, nutrient
      transport, and autophagy. mTORC2 is rapamycin insensitive and contains mTOR,
      rictor, mSIN1, PRR5, and mLST8. TORC2 in yeast and mammals mediates spatial
      control of cell growth by regulating the actin cytoskeleton. Thus, the 2 TOR
      complexes constitute an ancestral signaling network conserved throughout
      eukaryotic evolution to control the fundamental process of cell growth. As a
      central controller of cell growth, TOR plays a key role in development and aging
      and has been implicated in disorders such as cancer, cardiovascular disease,
      obesity, and diabetes. The challenge now is to understand the role of mTOR
      signaling to coordinate and integrate overall body growth in multicellular
      organisms.

PMID- 19100910
TI  - Steroid elimination-who, when, how?
AB  - Steroids have numerous side effects, many occurring early posttransplantation
      with relatively low prednisone doses. Consequently, investigators have attempted
      steroid minimization or withdrawal. The first attempts at steroid minimization
      used early low-dose steroids and were associated with an increased rate of acute
      rejection episodes, late graft dysfunction, and graft loss. Subsequent studies,
      with cyclosporine-based immunosuppression, attempted steroid withdrawal late
      posttransplantation (>3 months) in highly selected, clinically well, and
      immunologically low-risk recipients. Again, steroid withdrawal was associated
      with an increased risk of acute rejection episodes and these episodes were
      associated with graft dysfunction and increased graft loss. The development of
      new powerful immunosuppressive agents has led to renewed attempts at late
      prednisone withdrawal. These also have been associated with increased late
      rejection risk. A more exciting innovation has been the attempts at rapid
      discontinuation (<or=7 days posttransplantation) of prednisone with the following
      results: (1) Randomized studies have shown no significantly increased risk of
      acute rejection; (2) Randomized and nonrandomized studies have shown no increase
      in late graft loss; (3) Successful use in living and deceased donor recipients,
      primary and re-transplant recipients, adult and child recipients, white and black
      recipients, and low-risk and highly sensitized recipients; (4) About 80% of
      recipients remain prednisone-free long term. Recent nonrandomized data suggest
      that recipients who have an acute rejection episode while prednisone free are
      more likely to have a second rejection episode if they are returned to prednisone
      free immunosuppression. In these cases the acute rejection episode should be
      treated and long-term prednisone continued at 5 mg/d.

PMID- 19100911
TI  - New approaches to de novo immunosuppression and steroid elimination.
AB  - Calcineurin inhibitors (CNIs) and steroids, the cornerstones of most
      immunosuppressive regimens over the past 20 years, have undesirable chronic side
      effects, leading to the application of new strategies with sirolimus (SRL) and
      mycophenolate mofetil (MMF). We evaluated de novo CNI avoidance and early steroid
      withdrawal among 145 renal recipients randomized to receive either SRL (n = 71)
      or cyclosporine (CsA; n = 74). All patients received polyclonal antithymocyte
      globulin (ATG) for 5 days, MMF, and steroid withdrawal at 6 months (SPIESSER
      study). At 12 months, patient and graft survivals, incidence of biopsy-proven
      acute rejection (BPAR), and rates of steroid withdrawal were not statistically
      different namely, 97% versus 97%; 90% versus 93%, 14.3% versus 8.6%, and 82.8%
      versus 84.1%, respectively. Among patients who remained on treatment according to
      the protocol, the estimated glomerular filtration rate (eGFR) was significantly
      higher with SRL (69 +/- 19 versus 60 +/- 14 mL/min; P < .01). In another study of
      delayed introduction of SRL, 192 renal recipients were prospectively randomized
      at week 12 to switch from CsA to SRL (n = 95) or to continue CsA (n = 97; CONCEPT
      study). At 12 months, patient and graft survivals of the randomized patients,
      incidence of BPAR, and rates of steroid withdrawal were not significantly
      different: 100% versus 100%, 100% versus 98%, 17% versus 8%, and 72% versus 78%,
      respectively. Upon ITT eGFR was significantly higher with SRL (68.9 vs 64.4
      mL/min; P = .017). In both studies, a significant improvement in renal function
      was observed at 12 months among patients receiving a maintenance regimen with SRL
      plus MMF. Furthermore, steroids could be withdrawn in three quarters of the
      patients.

PMID- 19100912
TI  - Stratifying risk and targeting immunosuppressive strategies.
AB  - Despite short-term improvements, long-term outcomes in renal transplantation have
      not improved. Late graft loss arises as a result of immunologic and
      nonimmunologic insults that lead to chronic allograft nephropathy. One of the
      major nonimmunologic factors is the toxicity associated with current
      immunosuppressive regimens. In addition to these key factors, the current rate of
      death in renal transplant recipients with a functioning graft arises as a result
      of both cardiovascular risk and malignancy, as well as the growing challenge from
      infections. Renal transplant recipients are not a homogenous population, and
      donor factors add a further variable. Each individual recipient-donor combination
      will have its own unique set of risks of both graft loss and patient death. The
      choice of immunosuppressive regimens for an individual recipient needs to
      consider his or her risk profile, for early rejection and for late cardiovascular
      disease and malignancy. This meeting has considered all of these factors,
      together with strategies to reduce risk and offer potential for improved long
      term outcomes. This situation requires change in current practice and flexibility
      in our approach to the wide range of patients we manage on a daily basis.

PMID- 19100913
TI  - mTOR-understanding the clinical effects.
AB  - The target of rapamycin (TOR) is a highly conserved serine/threonine kinase that
      controls cell growth and metabolism in response to nutrients, growth factors,
      cellular energy, and stress. The TOR kinase, which was originally discovered in
      yeast, is also expressed in human cells as mammalian TOR (mTOR). In this review,
      we focus on how mTOR-inducible signals function in cell protection and cell
      survival of effector and regulatory T cells as well as its role in endothelial
      cell biology. We evaluate how signaling is important for vascular endothelial
      cell growth, survival, and proliferation; and we consider how the function of
      mTOR in endothelial cells may be clinically important in the rejection process.
      Understanding the biology of mTOR allows clinicians to use mTOR inhibitors
      optimally as therapeutics following solid organ transplantation.

PMID- 19100914
TI  - Predicting surgical outcome for advanced ovarian cancer, surgical standards of
      care, and the concept of kaizen.

PMID- 19100915
TI  - New membership model.

PMID- 19100916
TI  - A contemporary analysis of the ability of preoperative serum CA-125 to predict
      primary cytoreductive outcome in patients with advanced ovarian, tubal and
      peritoneal carcinoma.
AB  - OBJECTIVE: We previously reported that preoperative CA-125 may predict primary
      cytoreductive outcome in patients with stage III ovarian carcinoma (OC). The
      objective of this study was to perform a contemporary analysis of the ability of
      CA-125 to predict cytoreductive outcome in advanced OC since our programmatic
      change in surgical approach that currently incorporates the utilization of
      extensive upper abdominal procedures, as needed, to achieve maximal
      cytoreduction. METHODS: We reviewed the records of all patients with advanced
      ovarian, tubal or peritoneal carcinoma who underwent primary cytoreduction at our
      institution between 1/01 and 4/05. RESULTS: The study cohort included 277
      patients. Primary disease sites were: ovary, 232 (84%); tubal, 9 (3%); and
      peritoneum, 36 (13%). Stages were: IIIA, 6 (2%); IIIB, 12 (4%); IIIC, 215 (78%);
      and IV, 44 (16%). Tumor grades were: grade 1, 6 (2%); grade 2, 30 (11%); grade 3,
      233 (84%), and undifferentiated, 8 (3%). Cytoreductive outcomes were: no gross
      residual disease (RD), 68 (25%); <or=1 cm RD, 153 (55%); and >cm RD, 56 (20%).
      There was no threshold CA-125 level that accurately predicted cytoreductive
      outcome. However, with CA-125 values >500 U/mL, 50% (57/113) of patients required
      extensive upper abdominal surgery to achieve RD <or=1 cm, compared to 27% (25/93)
      for those with CA-125 <500 U/mL (P=0.001). CONCLUSION: Following our change in
      surgical paradigm that the incorporated extensive upper abdominal procedures to
      attain optimal debulking, preoperative CA-125 did not predict the primary
      cytoreductive outcome of patients with advanced ovarian, tubal, or peritoneal
      carcinoma. However, with a preoperative CA-125 >500 U/mL, extensive upper
      abdominal procedures were necessary in 50% of cases to achieve residual disease
      <or=1 cm. These data may be useful as part of preoperative surgical counseling
      and planning.

PMID- 19100917
TI  - Cholangiocarcinoma--what level of evidence should we have?

PMID- 19100918
TI  - Chronobiology in oncology.

PMID- 19100919
TI  - Timing of lethality from gastrointestinal syndrome in mice revisited.

PMID- 19100920
TI  - American Society for Therapeutic Radiology and Oncology (ASTRO) and American
      College of Radiology (ACR) Practice Guidelines for Intensity-Modulated Radiation
      Therapy (IMRT).

PMID- 19100921
TI  - Combination short-course preoperative irradiation, surgical resection, and
      reduced-field high-dose postoperative irradiation in the treatment of tumors
      involving the bone.
AB  - PURPOSE: To assess the feasibility and outcomes of combination short-course
      preoperative radiation, resection, and reduced-field (tumor bed without operative
      field coverage) high-dose postoperative radiation for patients with solid tumors
      mainly involving the spine and pelvis. METHODS AND MATERIALS: Between 1982 and
      2006, a total of 48 patients were treated using this treatment strategy for solid
      tumors involving bone. Radiation treatments used both photons and protons.
      RESULTS: Of those treated, 52% had chordoma, 31% had chondrosarcoma, 8% had
      osteosarcoma, and 4% had Ewing's sarcoma, with 71% involving the pelvis/sacrum
      and 21% elsewhere in the spine. Median preoperative dose was 20 Gy, with a median
      of 50.4 Gy postoperatively. With 31.8-month median follow-up, the 5-year overall
      survival (OS) rate is 65%; 5-year disease-free survival (DFS) rate, 53.8%; and 5
      year local control (LC) rate, 72%. There were no significant differences in OS,
      DFS, and LC according to histologic characteristics. Between primary and
      recurrent disease, there was no significant difference in OS rates (74.4% vs.
      51.4%, respectively; p = 0.128), in contrast to DFS (71.5% vs. 18.3%; p = 0.0014)
      and LC rates (88.9% vs. 30.9%; p = 0.0011) favoring primary disease. After
      resection, 10 patients experienced delayed wound healing that did not
      significantly impact on OS, DFS, or LC. CONCLUSION: This approach is promising
      for patients with bone sarcomas in which resection will likely yield
      close/positive margins. It appears to inhibit tumor seeding with an acceptable
      rate of wound-healing complications. Dose escalation is accomplished without high
      dose preoperative radiation (likely associated with higher rates of acute wound
      healing delays) or large-field postoperative radiation only (likely associated
      with late normal tissue toxicity). The LC and DFS rates are substantially better
      for patients with primary than recurrent sarcomas.

PMID- 19100922
TI  - Radiosensitization by inhibiting STAT1 in renal cell carcinoma.
AB  - PURPOSE: Renal cell carcinoma (RCC) has been historically regarded as a
      radioresistant malignancy, but the molecular mechanism underlying its
      radioresistance is not understood. This study investigated the role of signal
      transducer and activator of transcription 1 (STAT1), a transcription factor
      downstream of the interferon-signaling pathway, in radioresistant RCC. METHODS
      AND MATERIALS: The expressions of STAT1 and STAT3 in 164 human clear cell RCC
      samples, 47 papillary RCC samples, and 15 normal kidney tissue samples were
      examined by microarray expression profiling and immunohistochemistry. Western
      blotting was performed to evaluate the total and phosphorylated STAT1 expression
      in CRL-1932 (786-O) (human clear cell RCC), SKRC-39 (human papillary RCC), CCL
      116 (human fibroblast), and CRL-1441 (G-401) (human Wilms tumor). STAT1 was
      reduced or inhibited by fludarabine and siRNA, respectively, and the effects on
      radiation-induced cell death were investigated using clonogenic assays. RESULTS:
      STAT1 expression, but not STAT3 expression, was significantly greater in human
      RCC samples (p = 1.5 x 10(-8) for clear cell; and p = 3.6 x 10(-4) for
      papillary). Similarly, the expression of STAT1 was relatively greater in the two
      RCC cell lines. STAT1 expression was reduced by both fludarabine and siRNA,
      significantly increasing the radiosensitivity in both RCC cell lines. CONCLUSION:
      This is the first study reporting the overexpression of STAT1 in human clear cell
      and papillary RCC tissues. Radiosensitization in RCC cell lines was observed by a
      reduction or inhibition of STAT1 signaling, using fludarabine or siRNA. Our data
      suggest that STAT1 may play a key role in RCC radioresistance and manipulation of
      this pathway may enhance the efficacy of radiotherapy.

PMID- 19100923
TI  - Clinical evaluation of positioning verification using digital tomosynthesis and
      bony anatomy and soft tissues for prostate image-guided radiotherapy.
AB  - PURPOSE: To evaluate on-board digital tomosynthesis (DTS) for patient positioning
      vs. two-dimensional (2D) radiography and three-dimensional cone beam (CBCT).
      METHODS AND MATERIALS: A total of 92 image sessions from 9 prostate cancer
      patients were analyzed. An on-board image set was registered to a corresponding
      reference image set. Four pairs of image sets were used: digitally reconstructed
      radiographs vs. on-board orthogonal paired radiographs for the 2D method, coronal
      reference DTS vs. on-board coronal DTS for the coronal-DTS method, sagittal
      reference DTS vs. on-board sagittal DTS for the sagittal-DTS method, and planning
      CT vs. CBCT for the CBCT method. The registration results were compared. RESULTS:
      The systematic errors in all methods were <1 mm/1 degrees . When registering the
      bony anatomy, the mean vector difference was 0.21 +/- 0.11 cm between 2D and
      CBCT, 0.11 +/- 0.08 cm between CBCT and coronal DTS, and 0.14 +/- 0.07 cm between
      CBCT and sagittal DTS. The correlation between CBCT to DTS was stronger
      (coefficient = 0.92-0.95) than the correlation between 2D and CBCT or DTS
      (coefficient = 0.81-0.83). When registering the soft tissue, the mean vector
      difference was 0.18 +/- 0.11 cm between CBCT and coronal DTS and 0.29 +/- 0.17 cm
      between CBCT and sagittal DTS. The correlation coefficient of CBCT to sagittal
      DTS and to coronal DTS was 0.84 and 0.92, respectively. CONCLUSION: DTS could
      provide equivalent results to CBCT when the bony anatomy is used as landmarks for
      prostate image-guided radiotherapy. For soft tissue-based positioning
      verification, coronal DTS produced equivalent results to CBCT, but sagittal DTS
      alone was insufficient. DTS could allow for comparable soft tissue-based target
      localization with faster scanning time and a lower imaging dose compared with
      CBCT.

PMID- 19100924
TI  - Out-of-field dose equivalents delivered by passively scattered therapeutic proton
      beams for clinically relevant field configurations.
AB  - PURPOSE: Microdosimetric measurements were performed at Massachusetts General
      Hospital, Boston, MA, to assess the dose equivalent external to passively
      delivered proton fields for various clinical treatment scenarios. METHODS AND
      MATERIALS: Treatment fields evaluated included a prostate cancer field, cranial
      and spinal medulloblastoma fields, ocular melanoma field, and a field for an
      intracranial stereotactic treatment. Measurements were completed with patient
      specific configurations of clinically relevant treatment settings using a silicon
      on-insulator microdosimeter placed on the surface of and at various depths within
      a homogeneous Lucite phantom. The dose equivalent and average quality factor were
      assessed as a function of both lateral displacement from the treatment field edge
      and distance downstream of the beam's distal edge. RESULTS: Dose-equivalent value
      range was 8.3-0.3 mSv/Gy (2.5-60-cm lateral displacement) for a typical prostate
      cancer field, 10.8-0.58 mSv/Gy (2.5-40-cm lateral displacement) for the cranial
      medulloblastoma field, 2.5-0.58 mSv/Gy (5-20-cm lateral displacement) for the
      spinal medulloblastoma field, and 0.5-0.08 mSv/Gy (2.5-10-cm lateral
      displacement) for the ocular melanoma field. Measurements of external field dose
      equivalent for the stereotactic field case showed differences as high as 50%
      depending on the modality of beam collimation. Average quality factors derived
      from this work ranged from 2-7, with the value dependent on the position within
      the phantom in relation to the primary beam. CONCLUSIONS: This work provides a
      valuable and clinically relevant comparison of the external field dose
      equivalents for various passively scattered proton treatment fields.

PMID- 19100925
TI  - In vivo dosimetry using a linear Mosfet-array dosimeter to determine the urethra
      dose in 125I permanent prostate implants.
AB  - PURPOSE: In vivo dosimetry during brachytherapy of the prostate with (125)I seeds
      is challenging because of the high dose gradients and low photon energies
      involved. We present the results of a study using metal-oxide-semiconductor field
      effect transistor (MOSFET) dosimeters to evaluate the dose in the urethra after a
      permanent prostate implantation procedure. METHODS AND MATERIALS: Phantom
      measurements were made to validate the measurement technique, determine the
      measurement accuracy, and define action levels for clinical measurements. Patient
      measurements were performed with a MOSFET array in the urinary catheter
      immediately after the implantation procedure. A CT scan was performed, and dose
      values, calculated by the treatment planning system, were compared to in vivo
      dose values measured with MOSFET dosimeters. RESULTS: Corrections for temperature
      dependence of the MOSFET array response and photon attenuation in the catheter on
      the in vivo dose values are necessary. The overall uncertainty in the measurement
      procedure, determined in a simulation experiment, is 8.0% (1 SD). In vivo dose
      values were obtained for 17 patients. In the high-dose region (> 100 Gy),
      calculated and measured dose values agreed within 1.7% +/- 10.7% (1 SD). In the
      low-dose region outside the prostate (< 100 Gy), larger deviations occurred.
      CONCLUSIONS: MOSFET detectors are suitable for in vivo dosimetry during (125)I
      brachytherapy of prostate cancer. An action level of +/- 16% (2 SD) for detection
      of errors in the implantation procedure is achievable after validation of the
      detector system and measurement conditions.

PMID- 19100926
TI  - Fracture of a cross-linked polyethylene liner due to impingement.
AB  - We report a case of fracture at 2 years after implantation of a 50-kGy moderately
      cross-linked ultrahigh molecular weight polyethylene liner with an extended lip
      (Marathon, DePuy, Warsaw, IN). The extended lip section had fractured. The liner
      showed no oxidation. The articular surface was grossly deformed, likely due to
      wear, creep, and/or plastic deformation, and the liner showed no recovery of
      machining marks upon melting, indicating that some wear had occurred. Electron
      microscopy revealed fatigue striations on the fracture surface. The likely cause
      of failure was femoral neck impingement-induced wear and fatigue on the liner.

PMID- 19100927
TI  - Intermittent versus continuous bladder catheterization during labor: does it
      matter?

PMID- 19100928
TI  - The effect of intermittent versus continuous bladder catheterization on labor
      duration and postpartum urinary retention and infection: a randomized trial.
AB  - STUDY OBJECTIVE: To assess the effect of intermittent versus continuous bladder
      catheterization on labor duration and local anesthetic consumption. DESIGN:
      Randomized, controlled, prospective, single-blind trial. SETTING: University
      affiliated hospital. PATIENTS: 209 ASA physical status I and II, primiparous
      parturients who received patient-controlled epidural analgesia for labor.
      INTERVENTIONS: Patients were randomly allocated to either the intermittent
      bladder catheterization group (Group IC; n = 109) or the continuous
      catheterization group (Group CC; n = 100). MEASUREMENTS: Duration of the second
      stage of labor, dose of local anesthetics given, and primary outcomes were
      compared by group using the t-test for independent samples. Main secondary
      outcomes were postpartum urinary retention and rate of postpartum urinary tract
      infection (UTI; asymptomatic bacteruria). MAIN RESULTS: Duration of the second
      stage of labor was longer in Group CC than Group IC: 105 +/- 72 vs. 75 +/- 52 min
      (P = 0.002). This finding was associated with increased local anesthetic dose
      requirement in Group CC during both stages of labor (73 +/- 25 mL vs. 63 +/- 26
      mL; P = 0.005). The rate of UTI was similar (30%) in both study groups.
      CONCLUSION: Intermittent bladder catheterization was associated with shorter
      second-stage labor and less local anesthetic, but the same frequency of
      postpartum urinary retention and UTI was seen with both catheterization groups.

PMID- 19100929
TI  - Fiberoptic bronchoscopic view change of laryngopharyngeal tissues by different
      airway supporting techniques: comparison of patients with and without open mouth
      limitation.
AB  - STUDY OBJECTIVE: To investigate the changes in view of the laryngopharyngeal
      tissues on the fiberoptic bronchoscope (FOB) with different techniques of
      supporting the airway. DESIGN: Prospective, observational, stratified study.
      SETTING: University hospital. PATIENTS: 40 ASA physical status I, II, and III men
      undergoing elective oromaxillofacial surgery during general anesthesia with
      nasotracheal intubation. INTERVENTIONS: Patients were allocated into the normal
      mouth-opening group (Group N) or the limited mouth-opening group (Group L) to
      determine the grade of view of the laryngopharyngeal tissues exposed on the FOB,
      with 5 different airway supporting techniques: original airway position (OA),
      triple airway (TA), jaw thrust with opened mouth (JTO), jaw thrust with teeth
      protrusion (JTP), and head tilt with chin lift (HT). MEASUREMENT AND MAIN
      RESULTS: An adequate airway support was defined as having nearly full visibility
      of the entire glottic inlet. The investigator graded the vision of both anterior
      and posterior laryngopharyngeal tissues of each patient. All subjects experienced
      adequate airway support with the TA and HT airway supporting techniques. The TA
      airway supporting technique significantly moved the posterior laryngeal tissues
      more upward in Group N than Group L (P = 0.027). The JTP airway supporting
      technique provided adequate airway support for 14 of the 20 patients in Group N
      but only for two of the 20 Group L patients (P < .001). CONCLUSION: Both the TA
      and HT techniques provided adequate airway support for patients with and without
      limited mouth opening.

PMID- 19100930
TI  - Needs analysis for the development of a preoperative clinic protocol for
      perioperative beta-blocker therapy.
AB  - STUDY OBJECTIVE: To study the development and implementation of a hospital-wide
      protocol regarding preoperative beta-blocker therapy. DESIGN: Prospective,
      observational clinical study. SETTING: Preoperative test center at a university
      hospital. PATIENTS: 1,000 consecutive patients presenting for a preoperative
      visit and scheduled for same-day admit surgery. INTERVENTIONS: An algorithm of
      indications and contraindications for beta-blocker therapy was designed. Data
      were collected prospectively on 1,000 consecutive patients between June 1, 2004
      and August 31, 2004. MEASUREMENTS: Data collected included patient demographics,
      medication history, risk factors, indications and contraindications to beta
      blocker therapy, as well as surgical risk stratification and postoperative
      complications. MAIN RESULTS: 960 of the 1,000 patients underwent surgery and had
      complete information for the study collected. 169 patients (17.6%) were receiving
      beta blockers prior to evaluation. Of the patients having high-risk surgery, 72%
      had a major or minor indication for beta-blocker therapy without
      contraindication. Of the patients having intermediate or low-risk surgery, 10%
      had a major indication for beta blockers without contraindication. Overall, 52%
      (409/791) of the patients who were candidates for perioperative beta blockers
      were not receiving them. Some type of complication was experienced by 59 (6.1%)
      patients. CONCLUSIONS: Development, implementation, and monitoring of
      perioperative beta-blocker therapy protocols is necessary, as a significant
      number of appropriate patients do not receive this therapy.

PMID- 19100931
TI  - A cross-over, post-electroconvulsive therapy comparison of clinical recovery from
      rocuronium versus succinylcholine.
AB  - STUDY OBJECTIVE: To evaluate the effect of the neuromuscular blocking agent,
      rocuronium, on clinical recovery from electroconvulsive therapy (ECT) as compared
      with succinylcholine. DESIGN: Cross-over study. SETTING: University hospital.
      PATIENTS: 13 ASA physical status I and II patients, ages 18 to 60 years,
      receiving ECT three times a week. INTERVENTIONS: Each patient received either
      succinylcholine before the first ECT session (Group S) and rocuronium before the
      third ECT session (Group R). Muscle paralysis was produced with succinylcholine
      one mg kg(-1) intravenously (IV) or rocuronium 0.3 mg kg(-1) IV. Reversal of the
      residual neuromuscular block (Group R) was accomplished with 10 microg kg(-1)of
      atropine and 20 microg kg(-1)of neostigmine after completion of the ECT
      procedure. MEASUREMENTS: Motor seizure duration time, time to first spontaneous
      breathing, eye opening, head lift, and tongue depressor test were recorded. MAIN
      RESULT: Motor seizure duration and time to first spontaneous breath was longer
      (33.6 sec vs. 24.2 sec; 9.46 min vs 8.07 min, respectively) in the rocuronium
      group than the succinylcholine group. No significant difference was detected
      between the two groups in eye opening, head lift, or tongue depressor testing.
      CONCLUSION: Rocuronium, when used in conjunction with a reversal agent, may be an
      adequate alternative to succinylcholine as a neuromuscular blocker during ECT.

PMID- 19100932
TI  - Patient-controlled analgesia combined with either ondansetron or ondansetron plus
      prochlorperazine for control of pain and nausea and vomiting in patients
      undergoing abdominal surgery.
AB  - STUDY OBJECTIVE: To compare ondansetron with ondansetron plus prochlorperazine,
      added to a patient-controlled analgesia (PCA) solution for control of
      postoperative nausea and vomiting (PONV). DESIGN: Prospective, randomized, double
      blinded study. SETTING: University hospital. PATIENTS: 150 ASA physical status I,
      II, and III patients undergoing abdominal surgery. INTERVENTIONS: Patients were
      given a PCA morphine solution containing either 30 mg of ondansetron (Group O),
      30 mg of ondansetron plus 20 mg of prochlorperazine (Group OP), or no antiemetic
      (Group C; control group). MEASUREMENTS: Demographic data were recorded, along
      with anesthetic and surgical time, total fluid intake, frequency of
      Postanesthesia Care Unit (PACU) PONV, discharge time and length of stay,
      frequency of PONV while on the hospital floor, highest nausea scores, total PCA
      morphine use, and PCA utilization times. MAIN RESULTS: Demographic and
      intraoperative variables were similar in all groups. In the first 24 hours after
      surgery, nausea was higher in Group C than Group OP. Emesis in Group C was twice
      that of either Group O or Group OP. No differences were noted between groups in
      PACU PONV. Patients receiving ondansetron plus prochlorperazine when on the
      hospital floor had a lower frequency of nausea, while patients receiving
      ondansetron alone had a lower frequency of vomiting than did the control group.
      The adjusted odds of vomiting doubled for every 12 hours for Group C patients
      when receiving PCA. CONCLUSIONS: Combination antiemetics added to PCA reduced
      emetic symptoms after abdominal surgery.

PMID- 19100934
TI  - Postoperative bilateral adrenal hemorrhage: correlation between clinical and
      radiological signs.
AB  - The case of a patient who developed progressive hemodynamic instability during
      the late postoperative period following oncologic abdominal surgery is presented.
      Suspecting the onset of intraabdominal infection, we ordered a computed
      tomographic scan of the area, on which bilateral adrenal hemorrhage was observed.
      Adrenal function tests confirmed the presence of adrenal insufficiency.

PMID- 19100933
TI  - Pretreatment of rocuronium reduces the frequency and severity of etomidate
      induced myoclonus.
AB  - STUDY OBJECTIVE: To investigate the effect of pretreatment with a low dose of
      rocuronium on the occurrence of etomidate-induced myoclonus. DESIGN: Prospective,
      randomized, double-blinded study. SETTING: Medical center in South Korea.
      PATIENTS: 110 ASA physical status I, II, and III patients scheduled for elective
      cardiac or pulmonary surgery with general anesthesia. INTERVENTIONS: All patients
      were randomized to pretreatment with a low dose of rocuronium (0.06 mg/kg; Group
      R) or placebo (saline; Group S), followed three minutes later by etomidate (0.3
      mg/kg). MEASUREMENTS: Patients were monitored for myoclonic movements and pain on
      a scale of 0-3. Bispectral index (BIS) and electromyographic (EMG) activity were
      recorded continuously throughout the procedure. MAIN RESULTS: Frequency of
      myoclonus was significantly lower in Group R (25%) than in Group S (63%). In the
      latter group, there was no difference in the frequency of male (59%) and female
      (68%) patients experiencing myoclonus. In Group S, EMG activity and BIS were
      significantly increased in patients who experienced severe myoclonus, and BIS was
      well correlated with EMG activity. CONCLUSIONS: Pretreatment with a small dose of
      rocuronium before induction of anesthesia with etomidate significantly reduced
      the frequency of myoclonus.

PMID- 19100935
TI  - Pregnancy tests with end-stage renal disease.
AB  - Tests to ascertain pregnancy status are often obtained during preoperative
      evaluation, especially when there is a history of uncertain pregnancy or
      suggestion of current pregnancy. A serum pregnancy test, a beta-human chorionic
      gonadotropin (beta-HCG) level, was preoperatively obtained from a woman of
      childbearing age with end-stage renal disease (ESRD) with an unreliable history
      of irregular menstruation coupled with unprotected sexual activity. The beta-HCG
      was elevated in the range indicating pregnancy. Further work-up showed that this
      hormonal elevation was secondary to ESRD without pregnancy.

PMID- 19100936
TI  - Acute pulmonary edema from unrecognized high irrigation pressure in hysteroscopy:
      a report of two cases.
AB  - After two consecutive patients underwent hysteroscopy that was complicated by
      pulmonary edema, the pneumatically inflated pressure cuff machine was checked and
      found that the pressure gauge was in error, with actual pressure being twice that
      of the recorded number. High irrigation pressures with a seemingly normal amount
      of irrigation fluid may induce acute pulmonary edema.

PMID- 19100937
TI  - Anesthetic implications of Ellis-van Creveld syndrome.
AB  - Ellis-van Creveld syndrome (chondroectodermal or mesoectodermal dysplasia) is an
      autosomal recessive disorder. Initial reports of the syndrome identified a tetrad
      of clinical manifestations, including chondrodysplasia, postaxial polydactyly,
      ectodermal dysplasia, and congenital heart disease (CHD). Additional involvement
      may occur in organs of endodermal origin, such as the pulmonary, renal,
      gastrointestinal (hepatic and pancreatic), hematologic, and central nervous
      systems. The perioperative care of a 2-year, 8-month-old girl who underwent
      surgical correction of CHD is presented.

PMID- 19100938
TI  - Hidden but not forgotten: anesthesia responsibilities for intravenous catheter
      management.

PMID- 19100939
TI  - Heightened awareness of the thrombosis potential of drug-eluting stents may save
      lives.

PMID- 19100941
TI  - Does the orthopedic fracture table cause urinary retention?

PMID- 19100942
TI  - The amount of 8.4% sodium bicarbonate needed to neutralize the acidity of
      rocuronium so as to prevent injection pain.

PMID- 19100943
TI  - Techniques in Vascular and Interventional Radiology. Introduction.

PMID- 19100944
TI  - Clinical surveillance and monitoring of arteriovenous access for hemodialysis.
AB  - Clinical surveillance and monitoring of arteriovenous access for hemodialysis can
      best ensure long term access function. The failing access can be identified and
      referred for intervention prior to complete access failure. This article reviews
      the basic science of access function and the various techniques for detecting the
      failing access. These techniques are utilized by the dialysis unit staff and by
      the physician, often the interventionalist, who takes primary care of the access.
      A combination of various techniques to detect dysfunction and trend analysis of
      various parameters is most likely to identify in a timely manner, those patients
      who need intervention.

PMID- 19100945
TI  - Hemodialysis fistula interventions: diagnostic and treatment challenges and
      technical considerations.
AB  - End-stage renal disease is one of the main epidemiologic health problems and
      dialysis access continues to be the Achilles' heel of its treatment.
      Consequently, hemodialysis fistula maintenance is of great importance which can
      best be accomplished by close collaboration between primary care, nephrology,
      surgery and interventional radiology services, routine access monitoring as well
      as early intervention in cases of impending access failure. Also, knowledge and
      application of specific interventional techniques that are additionally described
      in this article may increase intervention efficiency, decrease the incidence of
      complications and overcome technical challenges thus improving procedural outcome
      and maximizing access patency rates.

PMID- 19100946
TI  - Endovascular management of the "failing to mature" arteriovenous fistula.
AB  - The "failing to mature" arteriovenous fistula (AVF) is frequently encountered
      among patients in need of hemodialysis (HD). It is essential that its prompt
      recognition and management are conducted in a timely manner to allow its use in
      HD. The physical examination is essential in early identification of the "failing
      to mature" AVF and helps guide initial endovascular management. In most
      instances, endovascular evaluation successfully identifies all the lesions that
      have contributed to AVF derangement and retarded its proper maturation. It is
      common to find juxta-arterial stenosis as well as venous stenosis in the body of
      the AVF, or its venous outflow tract. However, a wide spectrum of lesions can be
      seen, and in many instances, multiple lesions coexist in the same deranged AVF.
      Identifying and understanding the impact of all the lesions is a prerequisite for
      any intervention. Balloon angioplasty is the mainstay of management of stenotic
      lesions. Accessory vein obliteration or ligation is necessary in some cases.
      Procedure-related complications are low and are reduced by caution and
      experience. Overall, endovascular management is successful in converting the
      "failing to mature" AVF to usable HD access in the majority of cases, but
      multiple interventions may be needed in some before the AVF can be used for HD.
      Once usable, these AVFs have good long-term assisted patency rates. When
      endovascular management is unsuccessful or not possible, surgical revision of the
      AVF, or creation of a new AV vascular access is necessary.

PMID- 19100947
TI  - Tunneled dialysis catheters: pearls and pitfalls.
AB  - A review of the issues involved in placement of Tunneled Dialysis Catheter with a
      suggested scheme for maximizing good catheter placement and function.

PMID- 19100948
TI  - Selecting optimal hemodialysis catheters: material, design, advanced features,
      and preferences.
AB  - Hemodialysis catheters are a necessary evil. They provide an immediate and
      effective lifeline for hemodialysis patients, and their use is steadily
      increasing. This increasingly important role has lead to the development of many
      generations of dialysis catheters. Some aspects of novel designs have shown
      potential to reduce complications, while others provide options for physician
      insertion preference. The two major biomaterials for catheter construction are
      currently polyurethane and silicone, while copolymers such as carbothane are
      becoming more widespread. Catheter coatings such as heparin, antibiotics, and
      silver ion are designed to minimize thrombosis and infection. Finally, many lumen
      and tip designs are also available. These new features were designed to address
      common problems, including maintenance of adequate flow rate and prevention of
      thrombosis, fibrin sheath, and catheter-related infection. However, reliable data
      directly comparing these different designs and coatings are currently lacking.
      This communication reviews current hemodialysis catheters, including materials,
      design, and advanced features.

PMID- 19100949
TI  - Minimally invasive outpatient centers.
AB  - Minimally-invasive medicine has continually progressed from its beginning in the
      1960's. Evolution of technology and techniques have led to treatment of new
      disease states in minimally-invasive therapies. Now the venue of those therapies
      is shifting outpatient procedures from the hospital and into outpatient centers.

PMID- 19100950
TI  - Malfunction of dialysis catheters: management of fibrin sheath and related
      problems.
AB  - Suitable central venous access for hemodialysis is frequently required in
      patients with end-stage renal disease, whenever an arteriovenous fistula or
      peritoneal dialysis fails or is not a possibility. Ultimately, long-term dialysis
      via central access may result in dysfunctional catheter with problems such as
      malpositioning of catheter tip, fibrin sheath formation, thrombosis, infection,
      and bleeding. The role of interventional radiology is to deliver appropriate
      treatment to maintain patent and functional access, while minimizing the risk of
      venous occlusive disease. This article aims at describing different techniques
      and approaches for management of fibrin sheath associated with malfunctioning
      tunneled dialysis catheters, as well as to provide scientific evidence from the
      current literature.

PMID- 19100951
TI  - No more boring science, no more waste in clinical trials.

PMID- 19100952
TI  - Epigenetic regulation and the pathogenesis of systemic lupus erythematosus.
AB  - The pathogenesis of systemic lupus erythematosus (SLE) is incompletely
      understood. Studies in both lupus animal models and human disease indicate a
      clear role for epigenetic defects, particularly DNA methylation, in the
      pathogenesis of lupus. T-cell DNA from active lupus patients is hypomethylated,
      which results in overexpression of methylation-regulated genes, T-cell
      autoreactivity, and autoimmunity in vivo. Inducing an extracellular signal
      regulated kinase (ERK) signaling defect in T cells using a transgenic mouse model
      resulted in reduced DNA methyltransferase 1 (DNMT1) expression, overexpression of
      methylation-sensitive genes, and anti-double-stranded DNA (anti-dsDNA) antibody
      production. ERK signaling is known to be defective in lupus T cells, and this
      defect is now explained by impaired T-cell protein kinase C (PKC) delta
      activation. Herein, we discuss how defective epigenetic regulation is involved in
      the pathogenesis of lupus, which includes both DNA methylation and histone
      modification changes.

PMID- 19100953
TI  - Low serum 25 (OH) vitamin D levels (<32 ng/mL) are associated with reversible
      myositis-myalgia in statin-treated patients.
AB  - Our specific aims were to determine whether low serum 25 (OH) vitamin D (D2 + D3)
      (<32 ng/mL) was associated with myalgia in statin-treated patients and whether
      the myalgia could be reversed by vitamin D supplementation while continuing
      statins. After excluding subjects who took corticosteroids or supplemental
      vitamin D, serum 25 (OH) D was measured in 621 statin-treated patients, which
      consisted of 128 patients with myalgia at entry and 493 asymptomatic patients.
      The 128 myalgic patients had lower mean +/- standard deviation (SD) serum vitamin
      D than the 493 asymptomatic patients (28.6 +/- 13.2 vs 34.2 +/- 13.8 ng/mL, P <
      0.0001), but they did not differ (p > 0.05) by age, body mass index (BMI), type 2
      diabetes, or creatine kinase levels. By analysis of variance, which was adjusted
      for race, sex, and age, the least square mean (+/- standard error [SE]) serum
      vitamin D was lower in the 128 patients with myalgia than in the 493 asymptomatic
      patients (28.7 +/- 1.2 vs 34.3 +/- 0.6 ng/mL, P < 0.0001). Serum 25 (OH) D was
      low in 82 of 128 (64%) patients with myalgia versus 214 of 493 (43%) asymptomatic
      patients (chi(2) = 17.4, P < 0.0001). Of the 82 vitamin-D-deficient, myalgic
      patients, while continuing statins, 38 were given vitamin D (50,000 units/week
      for 12 weeks), with a resultant increase in serum vitamin D from 20.4 +/- 7.3 to
      48.2 +/- 17.9 ng/mL (P < 0.0001) and resolution of myalgia in 35 (92%). We
      speculate that symptomatic myalgia in statin-treated patients with concurrent
      vitamin D deficiency may reflect a reversible interaction between vitamin D
      deficiency and statins on skeletal muscle.

PMID- 19100954
TI  - Transcription factor decoys for activator protein-1 (AP-1) inhibit oxidative
      stress-induced proliferation and matrix metalloproteinases in rat cardiac
      fibroblasts.
AB  - Activator protein-1 (AP-1), which is a transcription factor, is implicated in the
      transcriptional regulation of a wide range of genes that participate in cell
      proliferation and extracellular matrix production. This investigation was
      performed to test the hypothesis that transfection of cardiac fibroblasts (CFs)
      with sufficient amounts of decoy oligodeoxynucleotides (ODNs) containing the AP-1
      binding site would result in binding to the transfactor AP-1, which would thereby
      prevent CF proliferation and matrix metalloproteinase (MMP) expression. CFs from
      Sprague-Dawley rat hearts were cultured and exposed to different concentrations
      of xanthine + xanthine oxidase (XXO) and AP-1 decoy ODNs. MMP expression was
      assayed after oxidative stress and transfection with AP-1 decoy ODNs by real-time
      quantitative polymerase chain reaction and Western blot. Cell growth was
      determined by the cell count. XXO significantly increased the DNA-binding
      activity of AP-1 in a dose-dependent manner. We found that transfection with AP-1
      decoy ODNs strongly inhibited XXO-induced CF proliferation and MMP gene
      expression in vitro. Taken together, our data demonstrate that AP-1 is a key
      transcription factor that mediates CF proliferation and MMP synthesis under
      oxidative stress. Transfection with AP-1 decoy ODNs may be a novel strategy to
      inhibit CF proliferation and MMP synthesis.

PMID- 19100955
TI  - Amyloid oligomers in diabetic and nondiabetic human pancreas.
AB  - The amyloid hypothesis of type 2 diabetes mellitus postulates that elevated
      levels of normally expressed monomeric proteins of human islet amyloid
      polypeptide (hIAPP) trigger oligomerization that independently causes fibril
      formation and disease progression. The aim of this study was to demonstrate the
      existence of amyloid oligomers in human pancreatic islets. Human pancreas tissues
      were obtained at autopsy of 8 nondiabetic control subjects (mean age = 75.8 +/-
      11.7 years, 4 males), 8 type 2 diabetic cases without islet amyloid (mean age =
      78.8 +/- 8.5 years, 4 males), and 8 type 2 diabetic patients with islet amyloid
      (mean age = 73.7 +/- 14.2 years, 4 males). Several markers for insulin, IAPP,
      amyloid fibrils (thioflavin T), and apoptosis (cleaved caspase-3) were used in
      combination with an oligomer-specific antibody. Two distinct forms of oligomers
      were found in pancreatic islets. Small spherical puncta were found in
      approximately 3% to 20% of the islet cells of nondiabetic subjects, and large
      curvilinear structures as extracellular oligomers were identified frequently in
      diabetic islets. Large oligomers were spatially localized adjacent to amyloid
      fibrils and were associated with apoptosis. This report demonstrates the presence
      of 2 morphologic classes of amyloid oligomers in human pancreatic islets. The
      observations warrant function studies to investigate the clinical implications of
      the amyloid oligomerization in the pathogenesis of type 2 diabetes.

PMID- 19100956
TI  - Enoxaparin-metformin and enoxaparin alone may safely reduce pregnancy loss.
AB  - Polycystic ovary syndrome (PCOS), thrombophilia, and hypofibrinolysis are
      associated with recurrent pregnancy loss (RPL) and spontaneous abortion (SAB). In
      28 Caucasian women, 21 women with PCOS (4 with previous thrombosis, 18 with 1 SAB
      or more, and 20 with 1 coagulation disorder or more), and 7 women with
      coagulation disorders-thrombi, we speculated that prospective treatment with
      enoxaparin-metformin or enoxaparin alone would successfully and safely promote
      healthy live births compared with previous untreated pregnancies. In 21 women
      with PCOS, metformin (1.5-2.55 g/day) was given before and during pregnancy with
      concurrent enoxaparin (60 mg/day). Of 21 PCOS women, 19 women had 40 previous
      untreated pregnancies, 7 had live births (18%), 3 had elective abortions (ABs)
      (8%), and 30 had SABs (75%). On enoxaparin-metformin, these 19 women had 24
      pregnancies, 20 live births (83%), and 4 SABs (17%); the SAB rate was 4.4-fold
      lower than previous untreated pregnancies (McNemar's s = 20.8, P < 0. 0001). Two
      women with PCOS without previous pregnancies, but with previous thrombosis, had 2
      pregnancies on enoxaparin-metformin and 2 live births. Of the 7 women with
      coagulation disorders-thrombi, 4 had 15 previous pregnancies without enoxaparin,
      with 6 live births (40%), 8 SABs (53%), and 1 elective AB (7%). On enoxaparin,
      these 4 women had 4 pregnancies, with 4 (100%) live births (McNemar's s = 8.0, P
      = 0.005). The other 3 women with coagulation disorders-thrombi had 4 pregnancies
      on enoxaparin with 4 live births. No adverse maternal-fetal side effects were
      reported on enoxaparin alone or enoxaparin-metformin. Enoxaparin-metformin
      reduces pregnancy loss in women with PCOS-coagulation disorders and in women with
      coagulation disorders-thrombi.

PMID- 19100957
TI  - Lipoprotein (a) [Lp(a)]: a possible link between migraine and stroke.
AB  - The biologic links by which migraine may be associated with vascular events are
      complex, and their exact mechanisms are currently unknown. Lipoprotein(a) [Lp(a)]
      has been suggested to be a risk factor for stroke, but no data are available
      concerning its role in migraine. The purpose of this study was to examine the
      role of Lp(a) in influencing migraine. Plasma levels of Lp(a) have been
      determined in 138 patients and in 120 control subjects comparable for age and
      sex. Abnormal Lp(a) levels, which are defined as more than 300 mg/L,
      significantly influenced the predisposition to migraine after adjustment for age,
      sex, and vascular traditional risk factors (odds ratio [OR], 3.4; 95% confidence
      interval [CI], 1.57-7.55; P = 0.002). By analyzing Lp(a) concentrations according
      to sex, we observed a significant difference in Lp(a) 300 mg/L cutoff value
      between patients and controls in the female (P = 0.002) but not in the male
      group. Abnormal Lp(a) levels were significantly associated with migraine at
      multivariate analysis after adjustment for age, hypertension, and smoking habit
      in the female (OR, 3.88; 95% CI, 1.59-9.51; P = 0.003) but not in the male group.
      In all, 24 of 141 patients (17%) and 17 of 112 controls (15.2%) were
      postmenopausal women. By analyzing abnormal Lp(a) concentrations, no significant
      difference between premenopausal and postmenopausal women in both the patient and
      the control group was found (P = 0.4 and P = 0.6, respectively). No difference in
      Lp(a) concentrations was observed between patients with and without aura, and in
      relation to headache intensity. The current study suggested evidence of high
      Lp(a) concentrations affecting migraines, possibly hypothesizing a novel link
      between migraine and stroke.

PMID- 19100958
TI  - Incidence and mortality rates of syncope in the United States.
AB  - PURPOSE: Syncope is a common cause of hospitalization in the US. The main
      objective of this study is to determine the incidence and mortality rates when
      patients are admitted with a principle diagnosis of syncope. METHODS: An
      observational cross-sectional study included patients with the principle
      diagnosis of syncope identified from the National Inpatient Sample database for
      the years 2000-2005. Incidence rate of syncope was adjusted according to the US
      Census data. In-hospital mortality and its predictors were identified by a
      logistic regression analysis, and Cochran-Armitage test was used for trend
      analysis. RESULTS: After data cleansing, 305,932 patients were included in the
      analysis. Adjusted incidence rate of syncope varied between 0.80 and 0.93 per
      1000 person-years and was unchanged over the years included in the analysis.
      Overall mortality rate is 0.28%, a trend that has not changed over the years
      (P=0.07). The odds ratio (OR) of death increased with age, becoming more
      prominent after age 40 years. Hospital mortality is higher in men (OR 1.49; 95%
      confidence interval [CI], 1.30-1.71) and in patients with higher comorbidity
      index (OR 1.39; 95% CI, 1.20-1.62) for moderate, and (OR 4.14; 95% CI, 3.05-5.61)
      for severe comorbidity index. The median cost of hospitalization is $8579, which
      increased by 3- to 11-fold if patients had a cardiac pacemaker or implantable
      cardioverter-defibrillator. CONCLUSIONS: Syncope remains a common cause of
      hospital admission. The hospital mortality rate for syncope is low. A better
      definition and a nationally implemented care path for syncope diagnosis could
      provide a substantial cost savings.

PMID- 19100959
TI  - Asthma in US seniors: part 2. Treatment. Seeing through the glass darkly.
AB  - BACKGROUND: We sought to identify the best evidence for treatment of asthmatic
      patients aged 65 years or more. METHODS: We used computer-assisted searches to
      identify randomized, controlled trials for asthma in the elderly that were
      published in English between 1950 and 2008. RESULTS: Small trials of an inhaled
      corticosteroid versus a leukotriene antagonist and an oral beta(2)-agonist versus
      placebo compose the controlled trial data on asthma therapy in seniors.
      Epidemiologic evidence suggests that the side effects of corticosteroids and beta
      agonists may be more common in the elderly than in younger populations.
      CONCLUSION: Seniors with asthma or comorbid conditions that are common in the
      elderly have been systematically excluded from asthma treatment trials. There is
      no compelling evidence to demonstrate the superiority of any pharmacologic
      therapy in these asthmatic patients. Evaluation of response to asthma treatment
      in clinical trials remains primarily symptom-based when symptoms have been shown
      to underestimate the severity of disease in seniors.

PMID- 19100960
TI  - "Dose-dependent" impact of recurrent cardiac events on mortality in patients with
      heart failure.
AB  - BACKGROUND: The mortality impact of recurrent cardiac hospitalizations has not
      been delineated in community-based heart failure patients. We determined if a
      "dose-dependent" relationship exists between heart failure events and death,
      accounting for temporal changes in age, comorbidities, and disease severity.
      METHODS: Among heart failure patients in the Enhanced Feedback For Effective
      Cardiac Treatment Study with onset between April 1999 and March 2001, we compared
      long-term survival (until March 2006) in those with recurrent heart failure or
      cardiovascular events, relative to those free of such events. RESULTS: In 9138
      patients, 28,442 person-years of follow-up were examined (mean age: 75.3 years,
      49.6% male). Recurrent heart failure events occurred 1, 2, 3, and >or=4 times in
      2352 (25.7%), 1020 (11.2%), 505 (5.5%), and 596 (6.5%) patients, respectively.
      Cardiovascular readmissions occurred 1, 2, 3, and >or=4 times in 2522 (27.6%),
      1509 (16.5%), 975 (10.7%), and 1672 (18.3%) patients, respectively. Compared with
      those without recurrent heart failure events, the adjusted relative mortality
      rates for 1, 2, 3, and >or=4 heart failure events were 2.41 (95% confidence
      interval [CI], 2.24-2.60), 3.00 (95% CI 2.72-3.32), 4.00 (95% CI, 3.51-4.56), and
      5.16 (95% CI, 4.55-5.85), respectively. Compared with those without
      cardiovascular events, the adjusted relative mortality rates for 1, 2, 3, and
      >or=4 cardiovascular events were 3.33 (95% CI, 3.05-3.63), 4.61 (95% CI, 4.16
      5.10), 6.29 (95% CI, 5.59-7.07), and 8.95 (95% CI, 8.05-9.95), respectively.
      CONCLUSIONS: The risk of death increases progressively and independently with
      each heart failure or cardiovascular event. The number of prior events predicts
      mortality and should be ascertained in patients with heart failure.

PMID- 19100961
TI  - Dynamic foot function and morphology in elite rugby league athletes of different
      ethnicity.
AB  - It has long been assumed that foot function and morphology differ between
      ethnicities. However, quantitative research proving or disproving this
      relationship is sparse. As a starting point, the objective of this study was to
      investigate the plantar loading characteristics and foot geometry of athletes
      from three ethnicities, being Caucasian, Maori and Pacific Islanders. Four
      plantar pressure parameters were compared in 28 male elite rugby league players
      using an EMED-AT plantar pressure distribution platform [Novel GmbH, Munich,
      Germany] and the five-step method. Foot geometry measures were also taken,
      including arch index, coefficient of spreading, hallux angle and sub-arch angle.
      Five trials were collected per foot at a self-selected speed. It was found that
      Caucasian and Maori subjects had a relatively wider forefoot than the Pacific
      Island subjects; however the Pacific Islanders' foot was found to be wider than
      both these ethnicities in absolute terms. While Caucasian subjects loaded the
      toes to a much greater extent than the Maori and Pacific Island subjects, the
      latter demonstrated a greater loading of the mid and forefoot regions. Pacific
      Island subjects revealed a significantly more pronounced hallux valgus angle as
      compared to the Caucasian and Maori subjects. The results of this study may be
      relevant for/should be taken into consideration in footwear design issues, where
      allowances need to be made during the design process for anatomical differences
      between ethnicities. However these observations cannot be generalised to whole
      ethnic populations, and further research is required on non-athletes to build on
      the current research findings.

PMID- 19100962
TI  - Involvement of p38 MAPK in regulation of MMP13 mRNA in chondrocytes in response
      to surviving stress to endoplasmic reticulum.
AB  - MMP13 is enriched in mature chondrocytes and considered a prime cause of ECM
      degradation in the osteoarthritic articular cartilage in temporomandibular
      joints. We asked whether surviving stress to the endoplasmic reticulum (ER) would
      upregulate transcription of MMP13, and if so, whether a cross-talk would exist
      between surviving ER stress and p38 MAPK pathways. Using C28/I2 chondrocyte cell
      line, ER stress was induced by thapsigargin and tunicamycin and upregulation of
      phosphorylated eIF2alpha and ATF4 protein was observed. Both thapsigargin and
      tunicamycin elevated the mRNA level of MMP13 and phosphorylation of p38 MAPK.
      Thapsigargin-induced MMP13 mRNA upregulation was significantly suppressed by
      SB203580, while its upregulation by tunicamycin was completely attenuated by
      SB203580. Those results support that homeostasis of chondrocytes is affected by
      the surviving ER stress through p38 MAPK pathways, suggesting a potential role of
      ER stress in joint diseases such as osteoarthritis.

PMID- 19100963
TI  - The aetiology of hypodontia: the prevalence, severity and location of hypodontia
      within families.
AB  - AIMS: Previous studies have indicated that hypodontia has a significantly higher
      prevalence in the relatives of affected individuals than in the general
      population. This study aims to examine further the roles of genetic and
      environmental factors in the aetiology of hypodontia by investigating the
      relationship between the severity and distribution of hypodontia between family
      members, and any discernable effect of maternal health during pregnancy and birth
      weight. METHODS AND RESULTS: 117 first degree relatives of 41 index patients were
      examined clinically and radiographically to identify the presence, severity and
      location of hypodontia. Both siblings and parents of index patients had a higher
      prevalence of hypodontia than the general population. The number and location of
      missing teeth was not related to the number and location of missing teeth in
      parents or siblings. The expression of hypodontia within a family was not
      affected by maternal health during pregnancy. CONCLUSIONS: The variation found in
      the expression of hypodontia within families suggests that its occurrence is not
      solely determined by genetic factors, but epigenetic and environmental factors
      probably also are important. This finding is consistent with a multifactorial
      aetiology for this condition.

PMID- 19100964
TI  - Multiple crown size variables of the upper incisors in patients with
      supernumerary teeth compared with controls.
AB  - AIMS: As part of ongoing studies of the aetiology of dental anomalies the aims of
      this study were to identify multiple components of tooth size of the upper
      permanent incisors in 34 patients with supernumerary teeth and to compare them
      with those in a control group to determine whether the presence of a
      supernumerary tooth has a local effect on the size of the surrounding dentition.
      METHODS AND RESULTS: The labial and occlusal aspects of the clinical crowns of
      the upper permanent central and lateral incisors on the study models of 74
      subjects were digitally imaged and measured using an image analysis system and
      automated macro (34 patients with supernumerary in the upper incisor region: 17
      males and 17 females and 40 controls: 20 males and 20 females). The macro-defined
      17 variables from each view. From the labial view these were: the mesio-distal
      and occluso-gingival length and additional measurements along 25 and 75% of the
      mesio-distal line and at 25, 50 and 75% along the occluso-gingival line such that
      all these sub-divisions extended to the periphery of the tooth. From the occlusal
      view these were: the mesio-distal and labio-lingual lengths, and additional
      variables that sub-divided the mesio-distal again at 25 and 75% along the length
      and at 25, 50 and 75% along the labio-lingual dimension. Principal component
      analysis (PCA) was used to identify the key factors with the most random
      variability. Comparisons were then carried out between the supernumerary cases
      and control group using 2-way ANOVA. Seven factors of tooth size for the upper
      central incisors and eight factors for the upper lateral incisors were extracted.
      Most of these variables were found to be larger in the supernumerary group than
      in the control. Statistically significant differences were found for 5 out of 7
      and 4 out of 8 for the upper central and lateral incisors respectively.
      CONCLUSIONS: A number of factors of tooth size were identified and found to be
      larger in the supernumerary group compared to the control (7 for upper central
      and 8 for upper lateral incisors); the majority reached the 0.05 significance
      level. Tooth crown size of the upper central incisor was affected more than that
      of the upper lateral incisor, supporting a local field effect.

PMID- 19100965
TI  - Interacting effects of worry and anxiety on attentional disengagement from
      threat.
AB  - Recent work suggests that the ability to disengage attention from threatening
      information is impaired in people who suffer from anxiety and dysphoria. It has
      been suggested that this impaired ability to disengage from threat might
      specifically be associated with the tendency to perseverate about threat (i.e.,
      worry), which is a main characteristic of anxiety disorders and a wide range of
      other psychopathologies. However, no studies have yet addressed this issue. The
      present study examined whether trait worry as well as worry intensity after
      experimental worry induction are associated with impaired ability to disengage
      attention from threatening cues (angry faces), independently from or in
      conjunction with anxiety. Sixty-one participants performed a visual cueing
      experiment that required detection of a target stimulus at one of two possible
      locations. Prior to the target neutral, happy or angry facial cues appeared at
      one of these two locations; when there is a relatively long period between the
      cue and the target (> 300 ms), an overall faster responding to invalidly cued
      trials relative to validly cued trials is believed to indicate inhibition of
      return (IOR) to a recently attended location. A reduced IOR for angry faces was
      only found when both trait worry and anxiety were high. When anxiety was kept
      constant, both trait worry and state worry were associated with enhanced IOR for
      neutral faces instead. The results seem to suggest that specific threat-related
      deficiencies in IOR may be a function of the co-occurrence of worry and anxiety.

PMID- 19100966
TI  - Positive allosteric modulation of mGluR5 receptors facilitates extinction of a
      cocaine contextual memory.
AB  - BACKGROUND: The perseverance of the motivational salience of drug-associated
      memories is an obstacle to the successful treatment of drug addiction and is
      often a causative factor in triggering relapse. METHODS: This study was intended
      to determine whether potentiation of type 5 metabotropic glutamate receptors
      (mGluR5), which are biochemically and structurally coupled to N-methyl-D
      aspartate (NMDA) receptors, would facilitate the extinction of a cocaine
      associated contextual memory as assessed by the conditioned place preference
      (CPP) paradigm in rats. Following the establishment of a cocaine CPP, rats were
      treated with the mGluR5 positive allosteric modulator 3-cyano-N-(1,3-diphenyl-1H
      pyrazol-5-yl)benzamide (CDPPB; 0.3, 3 and 30 mg/kg) before extinction test
      sessions. Additional groups of animals received 30 mg/kg CDPPB in combination
      with the mGluR5 antagonist 3-((2-methyl-1,3-thiazol-4-yl)ethynyl)pyridine (MTEP,
      1 mg/kg) or the NMDA receptor antagonist MK-801 (.1 mg/kg). RESULTS: CDPPB dose
      dependently facilitated the extinction of cocaine CPP, and these effects were not
      observed when animals were coadministered MTEP or MK-801. CDPPB failed to produce
      any evidence of neurotoxicity as assessed by FluoroJade C staining. CONCLUSIONS:
      Positive allosteric modulation of mGluR5 function facilitates the extinction of a
      cocaine-associated contextual memory, which may represent a novel approach toward
      enhancing extinction learning in the context of drug addiction.

PMID- 19100967
TI  - Abnormal affective responsiveness in attention-deficit/hyperactivity disorder:
      subtype differences.
AB  - BACKGROUND: Emotional-motivational dysfunctions likely contribute to attention
      deficit/hyperactivity disorder (ADHD), especially to hyperactive and impulsive
      symptoms. This study examined the affective modulation of the startle reflex in a
      large sample of ADHD patients. The aim was to compare subtypes of ADHD. METHODS:
      One hundred ninety-seven unmedicated adult ADHD patients (127 combined type [ADHD
      C]; 50 inattentive type [ADHD-I]; 20 hyperactive-impulsive type [ADHD-HI]) and
      128 healthy control subjects were examined. The affect-modulated startle response
      as well as valence and arousal ratings were assessed for pleasant, neutral, and
      unpleasant picture stimuli. RESULTS: Control subjects exhibited startle response
      attenuation and potentiation by pleasant and unpleasant pictures, respectively.
      In ADHD-HI, startle response was not attenuated by pleasant and not potentiated
      by unpleasant stimuli. In ADHD-C, startle response was not attenuated by pleasant
      pictures, and ADHD-I responded similar to control subjects but startle response
      was attenuated to a lesser degree by pleasant stimuli. The ADHD-HI group rated
      all pictures as more positive, and male ADHD-HI rated unpleasant stimuli as less
      arousing. CONCLUSIONS: This is the first study to assess the affect-modulated
      startle response in ADHD. It confirms emotional dysfunctions in these patients;
      all subtypes showed more or less diminished emotional reactions to pleasant
      stimuli. The hyperactive-impulsive type was also marked by blunted reactions to
      unpleasant stimuli. Results suggest that response patterns to emotional cues or
      reward may help to differentiate ADHD subtypes. Blunted emotional reactivity is
      especially pronounced in ADHD patients with symptoms of hyperactivity and
      impulsivity (ADHD-C, ADHD-HI).

PMID- 19100968
TI  - Preparation of high purity monodisperse oligosaccharides derived from mannuronan
      by size-exclusion chromatography followed by semi-preparative high-performance
      anion-exchange chromatography with pulsed amperometric detection.
AB  - Oligosaccharides of ([4)-beta-d-ManpA-(-->](n)) with a degree of polymerisation
      (DP) of 5, 10 and 15 were generated by partial acid hydrolysis of alginate
      mannuronan. These were subsequently purified by a combination of size-exclusion
      chromatography and semi-preparative high-performance anion-exchange
      chromatography with pulsed amperometric detection. The purity of the isolated
      oligosaccharides was greater than 96%. With automated operation of the
      chromatography system, milligram quantities can be generated over a period of a
      few days. Thus, our methodology now offers some significant advantages over
      earlier, including our own, protocols focused on uronic acid oligomers, where the
      final products are either not as pure or more starting material is needed to
      generate an equivalent yield of product. Removal of ammonium ions in collected
      fractions after size-exclusion chromatography and prior to freeze-drying was
      found to be essential to prevent the formation of imines and subsequent Maillard
      browning products.

PMID- 19100969
TI  - Gelation of high-methoxy pectin by enzymic de-esterification in the presence of
      calcium ions: a preliminary evaluation.
AB  - Cohesive gels have been obtained by de-esterification of 1.0wt% high-methoxy
      citrus pectin (degree of esterification approximately 68%) in the presence of
      Ca(2+) cations, using a commercial preparation (NovoShape) of fungal methyl
      esterase cloned from Aspergillus aculeatus. A convenient rate of network
      formation (gelation within approximately 30min) was achieved at an enzyme
      concentration of 0.2 PEU/g pectin. At a Ca(2+)-concentration of 40mM and
      incubation temperature of 20 degrees C, severe syneresis (>7% of sample mass) was
      observed, but release of fluid decreased with decreasing concentration of Ca(2+)
      and increasing temperature of incubation, becoming undetectable for 10mM Ca(2+)
      at 30 degrees C. Under these conditions, progressive development of solid-like
      character (storage modulus, G') was observed during 160min of enzymic de
      esterification, and the mechanical spectrum recorded at the end of the incubation
      period had the form typical of a biopolymer gel. On subsequent heating to 70
      degrees C, dissociation of the gel network (sigmoidal reduction in G' and G'')
      was observed. At or above the midpoint temperature of this melting process (
      approximately 50 degrees C), there was no indication of gel formation on enzymic
      de-esterification (at 50 or 60 degrees C). At lower temperatures (20, 30 and 40
      degrees C), the rate of gelation (assessed visually) showed no systematic
      increase as the incubation temperature was increased towards the temperature
      optimum of the enzyme ( approximately 50 degrees C). This unexpected behaviour is
      attributed to competition between faster de-esterification and slower formation
      of Ca(2+)-induced 'egg-box' junctions.

PMID- 19100970
TI  - Sex differences in left-right confusion depend on hemispheric asymmetry.
AB  - Numerous studies have reported that women believe they are more susceptible to
      left-right confusion than men. Indeed, some studies have also found sex
      differences in behavioural tasks. It has been suggested that women have more
      difficulties with left-right discrimination, because they are less lateralised
      than men and a lower degree of lateralisation might lead to more left-right
      confusion (LRC). However, those studies reporting more left-right confusion for
      women have been criticised because the tasks that have been used involved mental
      rotation, a spatial ability in which men typically excel. In the present study,
      34 right-handed women and 31 right-handed men completed two behavioural left
      right discrimination tasks, in which mental rotation was either experimentally
      controlled for or was not needed. To measure the degree of hemispheric asymmetry
      participants also completed a dichotic listening test. Although women were not
      less lateralised than men, both tasks consistently revealed that women were more
      susceptible to left-right confusion than men. However, only women with a
      significant right ear advantage in the dichotic listening test had more
      difficulties in LRC tasks than men. There was no sex difference in less
      lateralised participants. This finding suggests that the impact of functional
      verbal asymmetries on LRC is mediated by sex.

PMID- 19100971
TI  - Is the human primary motor cortex activated by muscular or direction-dependent
      features of observed movements?
AB  - Previous Transcranial Magnetic Stimulation (TMS) studies have shown that the
      observer's motor system is facilitated by the sole observation of motor actions.
      However, it has not been possible so far to decide whether the observer's motor
      system resonates primarily with the observed movement direction or the observed
      muscle activity, as both factors usually co-varied in these action observation
      studies. Here, we applied TMS to the wrist extensor and flexor during the
      observation of wrist motions such that the posture of the observer and the model
      in the video were either congruent or incongruent. Due to this manipulation, it
      was possible to disentangle whether the observer's primary motor cortex (M1) is
      facilitated in accordance to either the observed movement direction or the
      observed muscle activation. Findings revealed that M1 resonated predominantly
      according to muscle-specific rather than direction-specific parameters of
      observed movements. More specifically, muscle-specific facilitation was maximal
      during congruent postures and remained evident, even though to a lower extent,
      during incongruent postures in which muscle activation and movement direction
      parameters were discordant. Our findings support the hypothesis that M1
      contributes to action observation, by representing the observed movement in
      intrinsic, muscle-related coordinates. This transformation from extrinsic to
      intrinsic coordinates might be an important prerequisite for action understanding
      and imitation. Additionally, our data offer a neurophysiological explanation for
      interference that emerges when an action is performed while an incongruent action
      is observed.

PMID- 19100972
TI  - Freezing or escaping? Opposite modulations of empathic reactivity to the pain of
      others.
AB  - Perceiving pain in others may induce the covert simulation of both sensory and
      emotional components of others' pain experience. Previous transcranial magnetic
      stimulation (TMS) studies have investigated the motor counterpart of this
      resonant mapping by showing suppression of motor-evoked potentials (MEPs) during
      the observation of a needle entering body parts of another person. Here we
      explored whether MEPs recorded from an onlooker's hand (e.g., the right hand, TMS
      to the left motor cortex) are differentially influenced by the observation of
      painfully stimuli delivered to the same (right) or the opposite (left) hand in a
      model. Congruency between observed (model) and recorded (onlooker) hand brought
      about a reduction of MEPs amplitude. This resonant inhibitory response in the
      onlooker was specific for the muscle penetrated in the model. In contrast,
      observing pain on the model's hand opposite to that from which MEPs were recorded
      brought about a generalized increase of hand corticospinal excitability.
      Corticospinal inhibition and facilitation effects were comparable in the two
      hemispheres and specific for the corresponding and opposite hand. Results suggest
      that observing pain in another person's hand automatically induces the covert
      simulation of potentially adaptive freezing and avoidance responses in the
      onlooker's corticospinal system.

PMID- 19100973
TI  - Early electrophysiological correlates of meter and rhythm processing in music
      perception.
AB  - The two main characteristics of temporal structuring in music are meter and
      rhythm. The present experiment investigated the event-related potentials (ERP) of
      these two structural elements with a focus on differential effects of attended
      and unattended processing. The stimulus material consisted of an auditory rhythm
      presented repetitively to subjects in which metrical and rhythmical changes as
      well as pitch changes were inserted. Subjects were to detect and categorize
      either temporal changes (attended condition) or pitch changes (unattended
      condition). Furthermore, we compared a group of long-term trained subjects
      (musicians) to non-musicians. As expected, behavioural data revealed that trained
      subjects performed significantly better than untrained subjects. This effect was
      mainly due to the better detection of the meter deviants. Rhythm as well as meter
      changes elicited an early negative deflection compared to standard tones in the
      attended processing condition, while in the unattended processing condition only
      the rhythm change elicited this negative deflection. Both effects were found
      across all experimental subjects with no difference between the two groups. Thus,
      our data suggest that meter and rhythm perception could differ with respect to
      the time course of processing and lend credence to the notion of different
      neurophysiological processes underlying the auditory perception of rhythm and
      meter in music. Furthermore, the data indicate that non-musicians are as
      proficient as musicians when it comes to rhythm perception, suggesting that
      correct rhythm perception is crucial not only for musicians but for every
      individual.

PMID- 19100974
TI  - Spiral enteroscopy: a novel method of enteroscopy by using the Endo-Ease
      Discovery SB overtube and a pediatric colonoscope.
AB  - BACKGROUND: Pathologic diagnosis and therapeutic interventions on the small bowel
      have been difficult and challenging for gastroenterologists. In the last few
      years, significant advances have been made in this direction. New diagnostic and
      therapeutic modalities for visualizing the small bowel have been introduced.
      Furthermore, increased indications for small-bowel imaging and therapeutics have
      been recognized. However, the currently available methods have limitations, and
      development of newer, rapid, minimally invasive, safe, and readily available
      techniques is needed. OBJECTIVE: Our purpose was to evaluate the safety and
      efficacy of a novel method of spiral enteroscopy using a specialized overtube
      (Endo-Ease Discovery SB) with a pediatric colonoscope (PCF-140L). DESIGN: Case
      series. SETTING: Two international tertiary referral centers. PATIENTS: Twenty
      seven adult patients with obscure GI bleeding were enrolled in this study.
      INTERVENTION: Spiral enteroscopy with the Endo-Ease Discovery SB overtube and a
      pediatric colonoscope. MAIN OUTCOME MEASUREMENTS: Depth of insertion, time of
      procedure, and complications. RESULTS: Average depth of insertion was 176 cm
      (range 80-340 cm) from ligament of Treitz, and average time of procedure was 36.5
      minutes (range 90-65 minutes). Eleven patients had minor complications, which
      included minimal mucosal trauma and sore throat. LIMITATIONS: Small number of
      patients with a case series study design. CONCLUSIONS: Preliminary data suggest
      that use of Endo-Ease Discovery SB overtube for enteroscopy is a safe and
      effective technique for visualization of the small bowel.

PMID- 19100975
TI  - Initial experience with the prototype forward-viewing echoendoscope for
      therapeutic interventions other than pancreatic pseudocyst drainage (with
      videos).
AB  - BACKGROUND: The current oblique-viewing echoendoscope can occasionally be limited
      in its ability to perform therapeutic interventions because of the acute angle at
      which endoscopic accessories passed via the biopsy channel make contact with the
      gut wall. In an effort to overcome this limitation, a prototype forward-viewing
      echoendoscope was developed and successfully tested for performing transgastric
      drainage of pancreatic pseudocysts. OBJECTIVE: Evaluation of an initial
      experience with the prototype forward-viewing echoendoscope for performing
      interventions such as bile-duct drainage, pelvic-abscess drainage, and fiducial
      marker placement via the transduodenal and transrectal approaches. DESIGN: A
      retrospective study. SETTING: An academic tertiary-referral center. PATIENTS:
      Three patients. INTERVENTIONS: By using the prototype forward-viewing
      echoendoscope, transduodenal drainage of an obstructed bile duct, transrectal
      drainage of a pelvic abscess, and placement of fiducial markers in a rectal
      cancer were undertaken in 3 patients. MAIN OUTCOME MEASUREMENTS: To evaluate the
      feasibility of performing interventions via the transduodenal and transrectal
      approaches by using the prototype forward-viewing echoendoscope. OBSERVATIONS:
      The procedures were technically successful in all 3 patients, and no procedural
      complications were encountered. The passage of accessories and the deployment of
      stents were technically easy with the forward-viewing echoendoscope. In addition,
      there was no need to reorient the position of the echoendoscope when switching
      from a sonographic to endoscopic view while performing therapeutic interventions.
      LIMITATION: Small number of patients. CONCLUSIONS: It was feasible to perform
      interventions such as drainage of an obstructive bile duct and a pelvic abscess,
      and placement of fiducial markers via the transduodenal and transrectal
      approaches by using the prototype forward-viewing echoendoscope. Further studies
      that include larger numbers of patients are needed to evaluate the role of the
      forward-viewing echoendoscope for performing EUS-guided therapeutic
      interventions.

PMID- 19100976
TI  - Endoscopic removal of gallstones through a cholecystoduodenal fistula.

PMID- 19100977
TI  - Massive lower digestive bleeding caused by jejunal aneurysm.

PMID- 19100978
TI  - Sclerosing cholangitis from microscopic polyarteritis: an 8-year follow-up case
      report.

PMID- 19100979
TI  - Transaortic EUS-guided FNA in the diagnosis of lung tumors and lymph nodes.
AB  - BACKGROUND: Obtaining tissue from a para-aortal lymph node or tumor is a
      challenge that currently requires invasive surgical procedures. Para-aortic lung
      tumors can be clearly visualized by EUS. Although the accessibility of lesions
      adjacent to the esophagus is well documented, the para-aortic region has never
      been systematically explored. OBJECTIVE: To assess the feasibility, yield, and
      safety of transaortic biopsy specimens in the diagnosis of lung tumors and nodal
      masses located lateral to the aorta. DESIGN: A retrospective case series of 14
      consecutive patients. SETTING: Pulmonary Department, Leiden University Medical
      Center, Leiden, The Netherlands. PATIENTS: Fourteen patients with known or
      suspected lung cancer. Nine patients presented with a left-sided lung mass (mean
      size 27 mm), whereas 5 patients had an enlarged para-aortic node (mean size 16
      mm). INTERVENTIONS: Real-time EUS-guided transaortic biopsy of a para-aortic
      lesion. MAIN OUTCOME MEASUREMENTS: Feasibility, diagnostic yield, and
      complication rates of transaortic EUS-guided FNA (EUS-FNA). RESULTS: The final
      diagnosis was known in 12 patients (10 non-small-cell lung carcinoma [NSCLC], 1
      small-cell lung carcinoma [SCLC], and 1 renal-cell carcinoma). EUS-FNA
      established malignancy in 9 of 14 patients (64%) (8 NSCLC and 1 SCLC). One
      aspirate revealed reactive nodal tissue, and 4 demonstrated nonrepresentative
      material. Malignancy was further assessed in 3 patients after subsequent
      diagnostics. Transaortic FNA was found to be safe. In 2 patients, EUS images
      after biopsy were suspicious for a small para-aortic hematoma. These patients
      recovered uneventfully. CONCLUSIONS: These results demonstrate that a single EUS
      guided transaortic biopsy of para-aortic lymph nodes and tumors is a feasible and
      probably safe method that results in a diagnosis in the majority of cases.

PMID- 19100980
TI  - Success rate and complications of ERCP performed during hands-on training
      courses: a multicenter study in China.
AB  - BACKGROUND: Hands-on endoscopy workshops are popular and valuable sources for the
      continuing medical education of endoscopists. Concerns, however, exist regarding
      clinical outcomes of procedures performed during hands-on training of ERCP.
      OBJECTIVE: We compared the success rates and complications between patients in
      the hands-on training courses and matched control patients. DESIGN: A
      retrospective, multicenter study. SETTING: Seven endoscopy centers in mainland
      China. PATIENTS: All patients who underwent ERCP during hands-on training courses
      at GI endoscopy conferences in China between January 2002 and December 2006 were
      included. MAIN OUTCOME MEASUREMENTS: Clinical and endoscopic characteristics,
      including age, sex, indication, therapeutic intervention, success rate, and
      complication, were collected. Differences in ERCP outcomes between domestic and
      foreign mentors were also compared. Conference, patient, and endoscopist-related
      variables were analyzed for potential risk factors associated with post-ERCP
      complications. RESULTS: Nine conferences with hands-on ERCP training, including
      124 patients, were held at 7 endoscopy centers. There were no significant
      differences in the sex ratio, age, indication, and therapeutic intervention
      between patients for hands-on training (n = 124) and controls (n = 124). The
      success rates and overall complication rates were similar between the 2 groups
      (91.9% vs 92.7%, respectively, P = .811; 12.9% vs 9.7%, respectively, P = .422).
      Domestic mentors encountered more post-ERCP complications than foreign mentors
      (18.0% vs 0%, respectively, P = .001). Univariate analyses showed that a large
      scale conference (P = .004), first-time mentorship (P = .015), and small case
      volume for the mentor (P = .015) were significantly associated with post-ERCP
      complications. Nominal significance in univariate testing was removed when
      analyzed in a comprehensive multivariate setting. LIMITATIONS: A nonrandomized
      retrospective trial with only 7 centers (9 conferences). CONCLUSIONS: The success
      rate and overall complication rate were similar between patients in the hands-on
      training and those who had routine ERCP procedures. A large-scale conference,
      first-time mentorship, and small case volume for the mentor may be associated
      with post-ERCP complications.

PMID- 19100981
TI  - Esophageal sebaceous glands diagnosed after endoscopic mucosal resection.

PMID- 19100982
TI  - Modeling and controller performance assessment for a switched reluctance motor
      drive based on setpoint relay.
AB  - This paper considers the implementation of a current control method for switched
      reluctance motors (SRMs) and presents a novel approach to the accurate on-line
      modeling of an SRM drive. A simple autotuning technique for the SRM drives using
      a PWM controller is considered. Furthermore, conventional PI control and Internal
      Model Control (IMC) are considered to validate this method and present
      corresponding robust control analysis for the process. The control structures are
      comparatively analyzed using standard robustness measures for stability and
      performance. The proposed PWM controller is simulated and a hardware prototype is
      then implemented using digital signal processor control to evaluate the method
      using a 12/8, three-phase SRM. The experimental results of the SRM drive model
      validates the performance of the current loop.

PMID- 19100983
TI  - A method for determining minimal sets of markers for the estimation of center of
      mass, linear and angular momentum.
AB  - A new method is proposed for finding small sets of points on the body giving
      sufficient information for estimating the whole body center of mass (CoM), as
      well as the linear momenta (LM) and angular momenta (AM). In the underlying model
      each point (whose trajectory is tracked by a marker) is a point mass: Hence the
      body is represented by a simple system of point masses. The first step is to
      determine the appropriate set of points and the mass of each point, which is
      assumed to be specific for the movement performed. The distribution of the mass
      to each marker is determined from training data for which the true (or reference)
      trajectories of the CoM, LM or AM are known. This leads to a quadratic
      optimization problem with inequality constraints. The use of the method is
      demonstrated on data from discus throw. Results indicate reasonably small errors,
      considering the magnitude of other error sources, in CoM position (average
      magnitude of estimation error 1-2cm), and moderate errors in AM (13-20% of peak
      value).

PMID- 19100984
TI  - Oppugning the assumptions of spatial averaging of segment and joint orientations.
AB  - Movement scientists frequently calculate "arithmetic averages" when examining
      body segment or joint orientations. Such calculations appear routinely, yet are
      fundamentally flawed. Three-dimensional orientation data are computed as
      matrices, yet three-ordered Euler/Cardan/Bryant angle parameters are frequently
      used for interpretation. These parameters are not geometrically independent;
      thus, the conventional process of averaging each parameter is incorrect. The
      process of arithmetic averaging also assumes that the distances between data are
      linear (Euclidean); however, for the orientation data these distances are
      geodesically curved (Riemannian). Therefore we question (oppugn) whether use of
      the conventional averaging approach is an appropriate statistic. Fortunately,
      exact methods of averaging orientation data have been developed which both
      circumvent the parameterization issue, and explicitly acknowledge the Euclidean
      or Riemannian distance measures. The details of these matrix-based averaging
      methods are presented and their theoretical advantages discussed. The Euclidian
      and Riemannian approaches offer appealing advantages over the conventional
      technique. With respect to practical biomechanical relevancy, examinations of
      simulated data suggest that for sets of orientation data possessing
      characteristics of low dispersion, an isotropic distribution, and less than 30
      degrees second and third angle parameters, discrepancies with the conventional
      approach are less than 1.1 degrees . However, beyond these limits, arithmetic
      averaging can have substantive non-linear inaccuracies in all three parameterized
      angles. The biomechanics community is encouraged to recognize that limitations
      exist with the use of the conventional method of averaging orientations.
      Investigations requiring more robust spatial averaging over a broader range of
      orientations may benefit from the use of matrix-based Euclidean or Riemannian
      calculations.

PMID- 19100985
TI  - Phase distribution visualisation in continuous counter-current extraction.
AB  - Flow visualisation is essential when trying to understand hydrodynamic
      equilibrium in continuous counter-current extraction (CCCE) (also known as dual
      flow counter-current chromatography). The technique allows two immiscible liquid
      phases to be pumped through the spinning coil simultaneously in opposite
      directions. When this process was described previously it was assumed that the
      phases were evenly distributed throughout the coil. Visualisation studies by van
      den Heuvel and Sutherland in 2007 showed that this was not the case. A special
      centrifuge, where the coil is cantilevered so that the coil and the fluids inside
      the coil can be visualised, was used to study the distribution of the phases.
      Factorial experimental design was used to systematically study the effect of the
      starting conditions inside the coil on the phase distribution at equilibrium. For
      each experiment the eluted volumes and the volume of upper phase in the coil at
      the end of the experiment (at equilibrium) were recorded. In addition, two
      photographs were taken when the phases in the coil had reached equilibrium. One
      of these photographs was taken during the experiment when the phases were still
      being pumped through and one when the flow was stopped. The systematic
      experiments showed that the initial phase inside the coil has no effect on the
      phase distribution achieved at equilibrium. Statistical analysis also showed that
      the lower phase flow rate has double the effect on the phase distribution
      compared to the upper phase flow rate. From these visualisation studies, it can
      be concluded that the balance of the phases flowing through the coil at
      equilibrium is complex. The volumes of upper and lower phase and how they are
      distributed does influence the separation. It is important therefore to
      understand the relationship between respective flow rates and the phase
      distribution if peak elution is to be accurately predicted.

PMID- 19100986
TI  - Understanding molecular structures of silanes at buried polymer interfaces using
      sum frequency generation vibrational spectroscopy and relating interfacial
      structures to polymer adhesion.
AB  - The use of silane adhesion promoters to improve adhesion of elastomeric materials
      to polymers has become increasingly common in many industrial applications.
      However, little is understood about the molecular-level mechanisms of how
      adhesion promoters enhance adhesion. Here, sum frequency generation (SFG)
      vibrational spectroscopy was used to probe the buried interface between
      poly(ethylene terephthalate) (PET) and (3-glycidoxypropyl)trimethoxysilane (gamma
      GPS), and the interface between PET and a mixture of gamma-GPS and a
      methylvinylsiloxanol (MVS), a known adhesion-promoting mixture. Furthermore, the
      interfaces between PET and uncured silicone with incorporated silane or silane
      mixture and the interfaces between PET and cured silicone with incorporated
      silane or silane mixture were studied. The gamma-GPS methoxy groups were found to
      order at the polymer interface and the presence of MVS increased the interfacial
      segregation and/or order of gamma-GPS. For comparison, two other silanes, N
      octadecyltrimethoxysilane (OTMS) and (tridecafluoro-1,1,2,2
      tetrahydroctyl)trimethoxysilane (TDFTMS), as well as their mixtures with MVS were
      also studied at the various interfaces, and were found to exhibit different
      interfacial behaviors than gamma-GPS and the known silane adhesion-promoting
      mixture of gamma-GPS and MVS. Further, X-ray photoelectron spectroscopy (XPS) was
      used to investigate the exposed PET surfaces resulting from peeling the PET/cured
      silicone elastomer with TDFTMS and with the TDFTMS/MVS mixture interfaces, and it
      was shown that the fluorinated silane does segregate to the polymer interface.
      When correlated to adhesion testing results, it is inferred that segregation and
      ordering of the silane methoxy groups at the polymer/silane and polymer/silicone
      elastomer interfaces is crucial for adhesion promotion in this system.

PMID- 19100987
TI  - Gelling nature of aluminum soaps in oils.
AB  - Aluminum soaps are notable for their ability to form soap-hydrocarbon gels of
      high viscosity. For more than half a century, it has been believed that the
      gelling mechanism is due to a formation of polymeric chains of aluminum molecules
      with the aluminum atoms linking along the axis and with the fatty acid chain
      extended sideways. Here we report results from an investigation using high
      resolution electron microscopy and rheology measurements that clearly resolve the
      ambiguity. Our results reveal that the gelling mechanism stems from the formation
      of spherical nano-sized micelles from aluminum soap molecules, and those
      colloidal micelle particles then aggregate into networks of highly fractal and
      jammed structures. The earlier proposed polymer chain-like structure is
      definitely incorrect. The discovery of aluminum soap particles could expand
      application of these materials to new technologies.

PMID- 19100988
TI  - A thermodynamic analysis of gas adsorption on microporous materials: evaluation
      of energy heterogeneity.
AB  - This paper presents a thermodynamic isotherm derived from solution thermodynamics
      principles to describe gas adsorption on microporous materials. This isotherm
      relies on a potential relationship between the integral free energy of adsorption
      relative to saturation, Psi/RT, expressed by the Kiselev equation, and the
      variable Z = 1/-Ln(Pi), being Pi the relative pressure. A mathematical analysis
      reveals that the adsorption energy heterogeneity in the micropores is collected
      in a characteristic parameter of the isotherm, m, that can be related to the
      alpha parameter of the Dubinin-Astakhov isotherm in a simple way (m = alpha + 1).
      The isotherm also predicts a plateau in Psi/RT at extremely low pressures (Pi <
      10(-7)). Neimark's thermodynamic equation accounting for gas adsorption on
      mesoporous solids is found to be a particular case of the isotherm presented in
      this study. The Langmuir isotherm only shows consistency with the thermodynamic
      isotherm for a reduced combination of values of the relevant parameters, not
      usually found in common adsorbents. The suitability of the thermodynamic isotherm
      is experimentally assessed by testing a collection of microporous materials,
      including activated carbons, carbon nanotubes, and zeolites.

PMID- 19100989
TI  - Assessing the feasibility of hydrate deposition on pipeline walls--adhesion force
      measurements of clathrate hydrate particles on carbon steel.
AB  - Adhesive forces between cyclopentane (CyC5) hydrates and carbon steel (CS) were
      measured. These forces were found to be substantially lower than CyC5 hydrate
      CyC5 hydrate particle measurements and were also lower than ice-CS measurements.
      The measured adhesive forces were used in a force balance to predict particle
      removal from the pipeline wall, assuming no free water was present. The force
      balance predicted entrained hydrate particles of 3 microns and larger diameter
      would be removed at typical operating flow rates in offshore oil and gas
      pipelines. These predictions also suggest that hydrate deposition will not occur
      in stabilized (cold) flow practices.

PMID- 19100990
TI  - Synergistic adsorption of mixtures of cationic gemini and nonionic sugar-based
      surfactant on silica.
AB  - Adsorption behavior of cationic C(12)-C(4)-C(12) gemini surfactant on silica has
      been investigated, along with that of nonionic surfactant n-dodecyl-beta-D
      maltoside (DM). While DM alone shows meager adsorption on silica, because of the
      lack of any electrostatic adsorption, cationic gemini adsorbs significantly on
      the oppositely charged silica surface. Due to the electrostatic nature of
      cationic gemini adsorption on silica, solution pH affects adsorption of C(12)
      C(4)-C(12) gemini dramatically. Meanwhile, C(12)-C(4)-C(12) gemini hemimicelle
      size at silica/water interface does not seem to change with solution pH. For the
      mixtures of DM and cationic C(12)-C(4)-C(12) gemini, there is a sharp increase of
      DM adsorption at silica/water interface, up to 100 times more than DM alone.
      After mixing with DM, saturation adsorption of cationic C(12)-C(4)-C(12) gemini
      decreases, due to competition for adsorption sites from DM. At the same time, in
      its mixture with DM, there is an increased adsorption of C(12)-C(4)-C(12) gemini
      in the rising part of the adsorption isotherm. Hydrophobic chain-chain
      interactions, especially with two hydrophobic chains in one C(12)-C(4)-C(12)
      gemini molecule, and adsorbed C(12)-C(4)-C(12) gemini molecule acting as an
      anchor or nucleation sites for forming mixed aggregates with DM on silica
      surface, are attributed to the marked adsorption synergy between DM and cationic
      C(12)-C(4)-C(12) gemini. The adsorption of surfactants and their mixtures has a
      marked effect on silica surface charge and silica's wettability.

PMID- 19100991
TI  - Characterization and micellization of rhamnolipidic fractions and crude extracts
      produced by Pseudomonas aeruginosa mutant MIG-N146.
AB  - Two representative rhamnolipidic fractions, RL-F1 and RL-F2, produced by the P.
      aeruginosa mutant strain MIG-N146, were separated and chemically characterized by
      TLC, HPLC-MS, and FTIR. The RL-F1 fraction is predominantly mono-rhamnolipid
      homologues with a high content of one or two fatty acid moieties. The RL-F2
      fraction is mainly composed of di-rhamnosyl moieties with two hydrophobic tails.
      Micellization behavior was investigated to assess the physicochemical properties
      of the surfactants, RL-F1, RL-F2, and crude rhamnolipidic extracts. The
      variations in morphology of micelle formation and growth were examined by dynamic
      light scattering measurements as a function of surfactant concentration. Critical
      micelle concentration (CMC), average minimal surface tension (gamma(CMC)),
      saturated surface excess (Gamma(m)), mean surface area per molecule (S), and
      adsorption efficiency (pC(20)) were determined from the surface tension profiles
      and compared for the three surfactant systems. It was found that micelle growth
      was significantly enhanced by increasing rhamnolipid bulk concentration, which
      was most probably accompanied with an aggregate shape transition. Well-separated
      multi- or bi-modal distributions of particle size were observed in RL-F2 and the
      crude extracts solutions. The results of this study demonstrate that molecular
      architecture of different surfactant compositions profoundly influences the
      performance of rhamnolipidic surfactants.

PMID- 19100992
TI  - Comparison of exclusion volume corrections to the Poisson-Boltzmann equation for
      inhomogeneous electrolytes.
AB  - Comparisons are made of exclusion volume corrections to the Poisson-Boltzmann
      equation for the electric double layer next to a charged electrode. The exclusion
      volume terms treated are based mainly on (i) Langmuir type theories and (ii) the
      Bogoliubov-Born-Green-Yvon integral equations. The Langmuir type theories are
      modified to incorporate a distance of closest approach to the charged surface for
      comparison purposes. The theories are applied to the spherical electric double
      layer around a large macroion and the planar electric double layer. At high
      surface charge steric effects dominate when the Langmuir theories predict
      saturation in the counterion profile at and near contact, while the Bogoliubov
      Born-Green-Yvon based theories predict layering in the same profile.

PMID- 19100993
TI  - EDTA modified LDHs as Cu2+ scavengers: removal kinetics and sorbent stability.
AB  - EDTA modified layered double hydroxides (LDHs) were investigated as potential
      sorbents to remediate heavy metals pollution. The polidentate ligand was
      introduced by an exchange method in a Zn-Al-LDH, which takes place with partial
      erosion of the layers, causing the intercalation of [Zn(EDTA)](2-) complex
      instead of the ligand. [Cu(H(2)O)(6)](2+) cation was selected as a model cation
      to study the uptake mechanism, exploring the elimination kinetics from the first
      minutes up to the steady state. A flow injection analysis system coupled to an
      amperometric detector (FIA-AM) was applied to perform fast and reliable
      [Cu(H(2)O)(6)](2+) determinations in monodisperse solid-aqueous solution systems.
      Furthermore, the sorbent stability was determined as a function of the pH and the
      nitrate concentration. The [Cu(H(2)O)(6)](2+) elimination is produced by an
      exchange reaction with [Zn(EDTA)](2-) anions placed either in the solid
      interlayer or in the aqueous solution, this last being released from the sorbent.
      Additional [Cu(H(2)O)(6)](2+) removal is produced by Cu(OH)(2) precipitation at
      high copper concentrations due to the LDHs high pH buffering capacity. The
      sorbent removes [Cu(H(2)O)(6)](2+) with high affinity in a wide concentration
      range. The elimination process reaches equilibrium in less than 30 min and leaves
      metal cation concentrations lower than 0.05 ppm in the supernatants.

PMID- 19100994
TI  - Early language development of children at familial risk of dyslexia: speech
      perception and production.
AB  - Speech perception and speech production were examined in 3-year-old Dutch
      children at familial risk of developing dyslexia. Their performance in speech
      sound categorisation and their production of words was compared to that of age
      matched children with specific language impairment (SLI) and typically developing
      controls. We found that speech perception and production performance of children
      with SLI and children at familial risk of dyslexia was poorer than that of
      controls. The results of the at-risk and SLI-group were highly similar. Analysis
      of the individual data revealed that both groups contained subgroups with good
      and poorly performing children. Furthermore, their impaired expressive phonology
      seemed to be related to a deficit in speech perception. The findings indicate
      that both dyslexia and SLI can be explained by a multi-risk model which includes
      cognitive processes as well as genetic factors. LEARNING OUTCOMES: As a result of
      reading this paper the reader will be able to (1) learn about the relationship
      between language and literacy; (2) recognise that dyslexia and specific language
      impairment may show similar areas of language difficulties, and (3) understand
      that both disorders can be interpreted within a multirisk model, including
      cognitive processes as well as genetic factors.

PMID- 19100995
TI  - Mental models and other misconceptions in children's understanding of the earth.
AB  - This study investigated the claim (e.g., Vosniadou & Brewer's, 1992) that
      children have naive "mental models" of the earth and believe, for example, that
      the earth is flat or hollow. It tested the proposal that children appear to have
      these misconceptions because they find the researchers' tasks and questions to be
      confusing and ambiguous. Participants were 6- and 7-year-olds (N=127) who were
      given either the mental model theorists' original drawing task or a new version
      in which the same instructions and questions were rephrased to minimize ambiguity
      and, thus, possible misinterpretation. In response to the new version, children
      gave substantially more indication of having scientific understanding and less of
      having naive mental models, suggesting that the misconceptions reported by the
      mental model theorists are largely methodological artifacts. There were also
      differences between the responses to the original version and those reported by
      Vosniadou and Brewer, indicating that other factors, such as cohort and cultural
      effects, are also likely to help explain the discrepant findings of previous
      research.

PMID- 19100996
TI  - Increased oxidative stress in submitochondrial particles into the brain of rats
      submitted to the chronic mild stress paradigm.
AB  - Major depression is a common, serious and recurrent disorder, characterized by
      symptoms at the psychological, behavioral and physiological levels. Recent
      studies have suggested that reactive oxygen species (ROS) may play a role in the
      pathophysiology of bipolar disorder. The chronic mild stress (CMS) rat model has
      been used as an animal model of depression, since it induces some symptoms of a
      major depressive episode in humans (i.e. anhedonia). We investigated behavioral,
      physiological and neurochemical aspects of rats exposed for 40 days to CMS. Sweet
      food consumption, locomotor activity and body weight were assessed in stressed
      and control rats. We also investigated the potential involvement of ROS in the
      CMS model. Superoxide generation in submitochondrial particles from the rat
      hippocampus, prefrontal cortex and cortex was measured through superoxide
      dependent oxidation of epinephrine to adrenochrome in a submitochondrial extract.
      We report that sweet food intake was reduced in rats subjected to CMS compared to
      controls. Further, CMS animals failed to gain body weight compared with non
      stressed rats. Locomotor activity was not affected in stressed rats. An increase
      in superoxide production was detected in all brain structures analyzed. However,
      thiobarbituric acid reactive substances were increased only in cortex. In
      conclusion, these observations support the view that the CMS model of depression
      mimics alterations observed in depressed patients. The model affords a useful
      system in which to test the hypothesis that altered brain energy metabolism is
      associated with neuropsychiatric disorders.

PMID- 19100998
TI  - Multifocal deficits due to leukemic meningoradiculitis in chronic lymphocytic
      leukemia.
AB  - Symptomatic nervous system leukemic infiltration is rarely observed in CLL.
      Various clinical manifestations including headache, confusion, cranial nerve
      palsies, focal central deficits and peripheral neuropathies have been seldom
      reported, occurring in less than 1% of patients. We report herein 2 CLL patients
      with unusual clinical presentations of nervous system invasion. They presented
      multiple progressive peripheral deficits due to meningoradiculitis. In both, CSF
      immunophenotyping analysis identified a majority of T cells (>90%), and less than
      10% of B-CLL cells expressing CD5, CD19 and CD20. Our analyses revealed the
      transformation of CLL into an aggressive B-cell lymphoma in one case (Richter's
      syndrome). A post mortem study showed massive infiltration of cranial nerves and
      spinal roots by large B lymphomatous cells. In the other case, CNS oriented
      chemotherapy led to remission and total neurological recovery. In practice, the
      etiological diagnosis of neurological deficits in CLL patients is difficult. CSF
      analysis may be useful, requiring viral PCR, repeated cytological studies and
      immunophenotyping analysis. Although rare, leptomeningeal leukemic localization
      has to be discussed, even in the absence of overt Richter syndrome, and may
      require an early therapeutic test.

PMID- 19100997
TI  - Gray matter atrophy correlates with MS disability progression measured with MSFC
      but not EDSS.
AB  - BACKGROUND: Gray matter (GM) pathology is an important component of the multiple
      sclerosis (MS) disease process. Accelerated gray matter atrophy has been observed
      in MS patients, but its relationship to neurological disability is not defined.
      This study was done to determine the relationship between whole brain, GM, and
      white matter (WM) atrophy and MS disability progression. METHODS: Patients with
      MS and Clinically Isolated Syndromes (CIS), and age- and gender-matched healthy
      controls were entered into an observational protocol. Baseline brain parenchymal
      fraction (BPF), GM fraction, and WM fraction, and change over 4 years were
      correlated with sustained disability progression over the entire study duration.
      Disability progression was measured using the Multiple Sclerosis Functional
      Composite (MSFC) and the Expanded Disability Status Scale (EDSS). RESULTS:
      Seventy MS and CIS patients and 17 HCs were studied for an average of 6.6 years
      (range, 3.6-7.8 years). At the final visit, 7 patients were classified as CIS, 36
      as relapsing-remitting MS (RRMS), and 27 as secondary progressive MS (SPMS).
      Baseline whole brain, GM, and WM atrophy predicted EDSS >6.0 at the last study
      visit. Twenty-one (33%) patients worsened using the EDSS to define disability
      progression; 29 (46%) worsened using MSFC to define disability progression.
      Patients with MSFC progression had significantly higher GM atrophy rates compared
      with patients who were stable on MSFC. White matter atrophy was similar in
      patients with and without disability progression. Atrophy rates were not
      different in patients with or without disability progression defined using EDSS.
      CONCLUSIONS: Whole brain, GM, and WM atrophy predicted MS disability progression
      observed over the next 6.6 years. Gray matter atrophy rates over 4 years
      correlated with disability progression measured with the MSFC, but not EDSS. This
      indicates that MSFC defined disability progression is more closely linked to
      brain atrophy than EDSS defined disability progression, and provides important
      new insight into the poor correlation between MRI and clinical disability in MS.
      The findings confirm the clinical relevance of gray matter atrophy in MS.

PMID- 19100999
TI  - Improving male life expectancy in Birmingham.
AB  - On average, a man in Birmingham can expect to live 2 years less than men in the
      rest of England. Taken together, diseases of the circulatory system are
      responsible for the majority of deaths. This paper lays out the challenge faced
      and the interventions used to close that gap, with a particular focus on a large
      scale cardiovascular disease screening programme. Data from general
      practitioners' registers were used to target men over 40 years of age to be
      invited to special screening clinics to assess cardiovascular risk. The results
      obtained from almost 10,000 men are now being used to improve disease registers
      and to provide preventative treatments.

PMID- 19101000
TI  - Understanding how transport choices are affected by the environment and health:
      views expressed in a study on the use of carbon calculators.
AB  - OBJECTIVES: To examine the influence that the provision of environmental
      information might be able to make on personal travel behaviour through analysis
      of the views of members of the public expressed in a study for the UK Department
      for Transport on attitudes towards carbon calculator tools. STUDY DESIGN: A three
      stage qualitative survey taking an ideographic approach to analysing public
      attitudes to the use of carbon calculator tools in relation to making transport
      decisions. METHODS: Interviews and discussion groups with stakeholders, non-users
      and users providing extensive data that were analysed using the British Market
      Research Bureau's matrix mapping methodology. RESULTS: Despite considerable
      awareness of climate change as an issue, personal carbon emissions were not found
      to have much influence on personal transport choice, which could be seen as being
      dominated by issues of cost (both in time and money), comfort and convenience.
      CONCLUSIONS: The spatial and temporal dislocation of the cause and effects of
      climate change make it difficult to link the impacts of personal travel behaviour
      with specific activities. If environmental- and health-based information is to be
      provided as a lever to change travel behaviour, it may be necessary to provide
      information on issues such as local air pollution and personal health impacts in
      order to link wider benefits with a travel user's self-interest.

PMID- 19101001
TI  - CYP19 (cytochrome P450 aromatase) gene polymorphism in murrah buffalo heifers of
      different fertility performance.
AB  - The most common cause of infertility in buffaloes is anestrum. During late
      maturity the ovaries are in a state of true anestrum. One of the predominant
      causes of true anestrum is a low level of ovarian estrogens. The key enzyme in
      estrogen biosynthesis is cytochrome P450 aromatase, encoded by CYP19 gene. In the
      present study, CYP19 gene polymorphism was analyzed by Single Strand
      Conformational Polymorphism (SSCP) in buffaloes of different fertility
      performance. The SSCP and sequence analysis revealed 4 allelic variants in coding
      exons and introns which unaltered the protein sequence. However, a significant
      polymorphism (T/C heterozygote) was found near TATA binding protein region in
      regulatory part (a facet of promoter II) at position 23 of CYP19 exon 2, in all
      late matured and 50% of late maturing animals. Based on these observations and
      remarks of earlier workers, a hypothesis is proposed for the physiology of late
      maturity in buffaloes.

PMID- 19101002
TI  - Brainstem auditory evoked potentials in experimentally-induced bovine spongiform
      encephalopathy.
AB  - This study was carried out to evaluate the features of neurological dysfunction
      in experimentally-induced bovine spongiform encephalopathy (BSE)-infected cattle
      using brainstem auditory evoked potentials (BAEP). The progressive prolongation
      of peak latency of waves III and V was observed right-and-left bilaterally at the
      onset of neurological symptoms. The peak latency of wave V and the I-V interpeak
      latency (IPL) in BSE cattle 22 and 24 months after intracerebral inoculation were
      significantly (P<0.05) prolonged compared with the control cattle. In addition,
      the amplitude of the BAEP waves of the BSE cattle were low compared with the
      control cattle. Hearing loss occurred in the BSE cattle that showed advanced
      neurological symptoms such as tremor. It is thought that this BAEP data reflects
      a functional disorder in the central auditory nerve pathways characteristic of
      experimentally-induced BSE.

PMID- 19101003
TI  - Human immunodeficiency virus type 1-anchored CD40 ligand induces secretion of the
      chemokine interleukin-8 by human primary macrophages.
AB  - CD40 ligand (CD40L) is mainly expressed in activated CD4(+)T cells and interacts
      with CD40 on antigen-presenting cells to regulate both humoral and cellular
      immune responses. We previously reported that CD40L is acquired by emerging HIV-1
      particles. Here we demonstrate that both wild-type and a non-functional mutated
      form of CD40L are incorporated within HIV-1. Importantly, we show that wild-type
      CD40L remains functional since CD40L-bearing virions mediate NF-kappaB activation
      in a CD40-expressing reporter cell line and induce secretion of the chemokine IL
      8 by monocyte-derived macrophages. These results suggest a possible means
      exploited by HIV-1 to attract susceptible target cells to the site of infection,
      a process that might promote viral dissemination.

PMID- 19101004
TI  - West Nile virus genome amplification requires the functional activities of the
      proteasome.
AB  - The lifecycle of intracellular pathogens, especially viruses, is intimately tied
      to the macromolecular synthetic processes of their host cell. In the case of
      positive-stranded RNA viruses, the ability to translate and, thus, replicate
      their infecting genome is dependent upon hijacking host proteins. To identify
      proteins that participate in West Nile virus (WNV) replication, we tested the
      ability of siRNAs designed to knock-down the expression of a large subset of
      human genes to interfere with replication of WNV replicons. Here we report that
      multiple siRNAs for proteasome subunits interfered with WNV genome amplification.
      Specificity of the interference was shown by demonstrating that silencing
      proteasome subunits did not interfere with Venezuelan equine encephalitis virus
      replicons. Drugs that blocked proteasome activity were potent inhibitors of WNV
      genome amplification even if cells were treated 12 h after infection, indicating
      that the proteasome is required at a post-entry stage(s) of the WNV infection
      cycle.

PMID- 19101005
TI  - Characterization of dengue complex-reactive epitopes on dengue 3 virus envelope
      protein domain III.
AB  - The disease dengue (DEN) is caused by four genetically and serologically related
      viruses termed DENV-1, -2, -3, and -4. The DENV envelope (E) protein ectodomain
      can be divided into three structural domains designated ED1, ED2, and ED3. The
      ED3 contains the DENV type-specific and DENV complex-reactive (epitopes shared by
      DENV 1-4) antigenic sites. In this study the epitopes recognized by four DENV
      complex-reactive monoclonal antibodies (MAbs) with neutralizing activity were
      mapped on the DENV-3 ED3 using a combination of physical and biological
      techniques. Amino acid residues L306, K308, G381, I387, and W389 were critical
      for all four MAbs, with residues V305, E309, V310, K325, D382, A384, K386, and
      R391 being critical for various subsets of the MAbs. A previous study by our
      group (Gromowski, G.D., Barrett, N.D., Barrett, A.D., 2008. Characterization of
      dengue complex-specific neutralizing epitopes on the envelope protein domain III
      of dengue 2 virus. J. Virol 82, 8828-8837) characterized the same panel of MAbs
      with DENV-2. The location of the DENV complex-reactive antigenic site on the DENV
      2 and DENV-3 ED3s is similar; however, the critical residues for binding are not
      identical. Overall, this indicates that the DENV complex-reactive antigenic site
      on ED3 may be similar in location, but the surprising result is that DENV 2 and 3
      exhibit unique sets of residues defining the energetics of interaction to the
      same panel of MAbs. These results imply that the amino acid sequences of DENV
      define a unique interaction network among these residues in spite of the fact
      that all flavivirus ED3s to date assume the same structural fold.

PMID- 19101006
TI  - Establishment of an Alert Level Framework for cyanobacteria in drinking water
      resources by using the Algae Online Analyser for monitoring cyanobacterial
      chlorophyll a.
AB  - The Algae Online Analyser (AOA) fluorometer simultaneously distinguishes four
      different phytoplankton groups by their specific fluorescence spectra and thus
      allows for real-time in-situ chlorophyll a measurements per algal group. This AOA
      was used for monitoring cyanobacterial chlorophyll a in the drinking water at the
      Bronislawow Bay abstraction point in Sulejow Reservoir (Poland). The main goal of
      this research was to develop an early warning method for the detection of
      cyanobacterial biovolume in the source water, in order to establish an Alert
      Level Framework for the drinking water abstraction point in Sulejow Reservoir. A
      positive correlation between cyanobacterial biovolume, as determined by
      conventional methods, and cyanobacterial chlorophyll a, as measured by the AOA,
      was found (p<0.05). The results of this study were used to determine threshold
      values for the Alert Level Framework, based on cyanobacterial chlorophyll a
      concentrations in the source water of Sulejow Reservoir. The presented threshold
      values are determined specifically for this abstraction point, but the principles
      can be applied to other locations.

PMID- 19101007
TI  - Differential response of arsenic stress in two varieties of Brassica juncea L.
AB  - Present study showed the toxicity caused by Arsenite (As(III)) and its
      detoxification responses in two varieties (Varuna and Pusa Bold) of Brassica
      juncea. Comparisons were made in leaves and roots of both the varieties, which
      showed that the accumulation pattern in both the varieties were dose and duration
      dependent, being more in roots for two days and in leaves for four days.
      Increase/decrease of antioxidant enzymes activities (SOD, CAT, GPX) showed not
      much changes at the given concentrations except that the enzyme activities showed
      significant increase at the lower concentrations. Semi quantitative RT-PCR
      analysis of PCS showed more expression of its transcript in P. Bold as compared
      to Varuna variety due to As(III) stress. The analysis of isoenzyme pattern in
      leaves of P. Bold showed five and two major bands of SOD and GPX, respectively.
      As(III) treatment leads to the activation of MAPK activity indicating role of
      this important cascade in transducing As(III) mediated signals. The data
      presented indicates the differential responses in both the varieties and also
      that the increased tolerance in P. Bold may be due to the defensive role of
      antioxidant enzymes, induction of MAPK and up regulation of PCS transcript which
      is responsible for the production of metal binding peptides.

PMID- 19101008
TI  - Adsorption studies of the herbicide simazine in agricultural soils of the
      Aconcagua valley, central Chile.
AB  - Simazine is a s-triazine herbicide that has been applied worldwide for
      agriculture. This herbicide is the second most commonly detected pesticide in
      surface and groundwater in the United States, Europe and Australia. In this
      study, simazine adsorption behaviour was studied in two agricultural soils of the
      Aconcagua valley, central Chile. The two studied soils were soil A (loam, 8.5%
      organic matter content) and soil B (clay-loam, 3.5% organic matter content).
      Three times higher simazine adsorption capacity was observed in soil A (68.03 mg
      kg(-1)) compared to soil B (22.03 mg kg(-1)). The simazine adsorption
      distribution coefficients (K(d)) were 9.32 L kg(-1) for soil A and 7.74 L kg(-1)
      for soil B. The simazine adsorption enthalpy in soil A was -21.0 kJ mol(-1) while
      in soil B the adsorption enthalpy value was -11.5 kJ mol(-1). These results
      indicate that simazine adsorption process in these soils is exothermic, governing
      H bonds the adsorption process of simazine in both the loam and clay-loam soils.
      These results and the potentiometric profiles of both soils, suggest that
      simazine adsorption in soil A is mainly governed by simazine-organic matter
      interactions and in soil B by simazine-clay interactions. The understanding of
      simazine sorption-desorption processes is essential to determine the pesticide
      fate and availability in soil for pest control, biodegradation, runoff and
      leaching.

PMID- 19101009
TI  - Specific accumulation of perfluorochemicals in harbor seals (Phoca vitulina
      concolor) from the northwest Atlantic.
AB  - Concentrations of perfluorochemicals (PFCs) including perfluoroalkylsulfonates
      (PFSAs), and perfluoroalkylcarboxylates (PFCAs) were determined in liver of
      harbor seals (n=68) collected from the northwest Atlantic between 2000 and 2007.
      Of ten PFCs measured, perfluorooctane sulfonate (PFOS) concentrations were the
      highest in liver (8-1388 ng/g, ww), followed by perfluoroundecanoic acid (PFUnDA)
      (<1-30.7 ng/g, ww). An unusual accumulation profile of long-chain (C7-C12) PFCAs,
      and the predominance of PFUnDA, followed by PFNA in seal liver suggested that
      fluorotelomer alcohols (FTOHs) may be a major source of PFCAs in the northwest
      Atlantic. No gender-related differences in the concentrations of individual PFCs
      or total PFCs were found. Concentrations of PFOS and PFDS were higher in tissues
      of the pups than the adults, whereas concentrations of the PFCAs were similar
      between pups and adults. PFOS concentrations in the pups were 2.6-fold higher
      than those in the adult females, suggesting the importance of maternal transfer
      of PFCs. Hepatic PFOS concentrations were strongly, positively correlated with
      PFOSA, PFDS and individual PFCAs, indicating that harbor seals are exposed
      simultaneously to these compounds. Temporal comparisons of hepatic PFC
      concentrations showed a marginal increase of PFOS and PFCAs in the adult seals
      from 2000 to 2007. Unlike the spatial trend observed for polychlorinated
      biphenyls (PCBs), no south to north (urban-rural-remote) decreasing trend was
      observed for PFCs, suggesting the presence of diffuse sources of PFC
      contamination throughout the northwest Atlantic.

PMID- 19101010
TI  - Evaluation of three-year monitoring with biomarkers in fish following the
      Prestige oil spill (N Spain).
AB  - A previous study using a suite of hepatic enzymatic biomarker in two demersal
      fish species (Lepidorhombus boscii and Callionymus lyra) indicated exposure of
      the fish to the hydrocarbons in the oil spilled by the Prestige five months after
      the accident. The main objective of this follow-up study is to determine whether
      the same biomarkers in both fish species show any significant variations in
      responses over the years following the Prestige oil spill. Detoxification and
      antioxidant enzyme measurements--of ethoxyresorufin-O-deethylase (EROD),
      glutathione-S-transferase (GST), glutathione reductase (GR) and catalase (CAT)-
      were taken from immature specimens. The results show significant lowering of
      biomarker activity two and three-years after the oil spill, indicating a
      decreasing level of exposure of the fish to residual hydrocarbons associated with
      the spillage (p < 0.01) and a recovery to baseline levels existing before the
      accident. Overall, spatial biomarker patterns over time are in agreement with the
      oil slick trajectories and the spatial distribution of tar aggregates found on
      the bottom shelf after the accident. The results also indicate that the Prestige
      oil spill had an impact on sublethal responses in fish not only in inshore areas,
      but also in offshore areas along the middle/outer northern Iberian shelf. In both
      species, EROD activity was found to be the most discriminating biomarker.

PMID- 19101011
TI  - Acute exposure of the aquatic macrophyte Callitriche obtusangula to the herbicide
      oxadiazon: the protective role of N-acetylcysteine.
AB  - In this study we investigated the acute exposure of the aquatic macrophyte
      Callitriche obtusangula to the herbicide oxadiazon (Ronstar). The toxic effects
      on C. obtusangula were evaluated, 24h after exposure, by assessing visible
      necrotic leaf lesions and, 12 h after exposure, via analyses of dead cells and
      hydrogen peroxide (H2O2) deposits localized by histocytochemical analysis with
      Trypan blue and 3,3'-diaminobenzidine (DAB), respectively. As a result, we found
      that 0.1275 microg L(-1) a.i. (active ingredient) oxadiazon was the maximum
      concentration that produced no observable adverse effects (NOAEC) both at leaf
      and tissue levels, at any considered exposure time. Additionally, we assayed the
      protective effect of pre-treatment with 0.25 mM N-acetylcysteine (NAC), a
      cysteine donor, on the damage caused by the toxic herbicidal dose of 6.37 microg
      L(-1) a.i to C. obtusangula, correlating the NAC observed protection to the
      direct H2O2-scavenging and to the enhancement of glutathione parameters. NAC
      treated plants showed a fourfold increase in the GSH (reduced glutathione)+GSSG
      (oxidised glutathione) content (149.2 nmol g(-1) FW) compared to controls (36.1
      nmol g(-1) FW); in the NAC+oxadiazon treatments, the GSH+GSSG content was more
      than fivefold higher (202.1 nmol g(-1) FW). GSH showed a similar trend in NAC and
      NAC+oxadiazon treatments, being six- (130.0 nmol g(-1) FW) and eightfold (185.0
      nmol g(-1) FW) higher, respectively, compared to controls (20.7 nmol g(-1) FW).
      Accordingly, the GSH/GSSG ratio in NAC- and NAC+oxadiazon-treated plants was
      significantly increased compared to controls, indicating alleviation of oxidative
      stress.

PMID- 19101012
TI  - Dioxin contamination after an accidental fire in the municipal landfill of
      Tagarades, Thessaloniki, Greece.
AB  - We report here a case study of dioxin contamination after a fire in the public
      landfill of Tagarades, which is situated southeast of Thessaloniki, Greece. The
      aim of this study was to determine the levels of PCDD/Fs and PCBs in food samples
      of meat, eggs, dairy products and vegetables, collected near the affected area,
      and to compare them with the usual levels found in Greek food. Soil samples were
      also gathered from various sites at a distance up to 5km from the landfill. Some
      food samples were found above the limits specified by the EU, while all food
      samples were above the usual levels of Greek food. The contaminated products were
      appropriately destroyed. The results of the soil and olive samples indicate a
      reverse correlation between dioxin contamination and distance from the
      contamination source. It should be noted that PCB levels were normal in all
      analyzed samples.

PMID- 19101013
TI  - Enhanced dechlorination of chlorobenzene and in situ dry sorption of resultant Cl
      compounds by CaO and Na2CO3 sorbent beds incorporated with Fe2O3.
AB  - The dechlorination of C(6)H(5)Cl and the in situ dry sorption of Cl-compounds
      produced by C(6)H(5)Cl decomposition in an alkaline sorbent of CaO or Na(2)CO(3)
      incorporated with Fe(2)O(3) were studied. A sample gas containing C(6)H(5)Cl at
      an initial concentration of 500 ppm balanced by either N(2), O(2) (5%)-N(2) or
      H(2)O (10%)-N(2) carrier gas was introduced into a lab-scale quartz tube reactor
      where CaO or Na(2)CO(3) sorbent was packed with Fe(2)O(3). Subsequently, the
      effect of Fe(2)O(3) addition to CaO or Na(2)CO(3) on the removal of C(6)H(5)Cl,
      achieved by the decomposition of C(6)H(5)Cl as well as the dry sorption of Cl
      compounds produced by C(6)H(5)Cl decomposition, was investigated. It was found
      that the decomposition of C(6)H(5)Cl in CaO or Na(2)CO(3) sorbent bed
      incorporated with Fe(2)O(3) occurred in the lower temperatures, compared to the
      case when only CaO or Na(2)CO(3) sorbent bed was used. Thus, Fe(2)O(3) was found
      to play a catalytic role in the oxidative decomposition of C(6)H(5)Cl. Further,
      the decomposition of C(6)H(5)Cl in a bed containing only Fe(2)O(3) was promoted
      by the presence of O(2) and H(2)O in the reaction atmosphere. Moreover, a higher
      amount of Cl was absorbed in the combined CaO/Fe(2)O(3) and Na(2)CO(3)/Fe(2)O(3)
      beds, compared to the absorption of Cl-compounds in only CaO or Na(2)CO(3)
      sorbent bed. Finally, the comparison of CaO and Na(2)CO(3) sorbents showed that
      the decomposition of C(6)H(5)Cl and the in situ dry sorption of the resultant Cl
      compounds in the combined Na(2)CO(3) and Fe(2)O(3) beds were higher than those in
      the combined CaO and Fe(2)O(3) beds.

PMID- 19101014
TI  - The effect of bacteria on the sensitivity of microalgae to copper in laboratory
      bioassays.
AB  - Although single-species laboratory toxicity tests with microalgae are sensitive
      and highly reproducible, they lack environmental realism. Interactions between
      algae and their associated bacteria, either in the plankton or in biofilms, may
      alter algal sensitivity to contaminants, which are not mimicked in laboratory
      toxicity tests. This study investigated the effects of simple algal-bacterial
      relationships on the sensitivity of laboratory-cultured algae to copper using 72
      h algal growth-rate inhibition bioassays. Four species of microalgae were used,
      two isolates of each; a strain of algae with no microscopically visible and no
      culturable bacteria present (operationally defined as axenic) and a non-axenic
      strain. The four algae used were the marine diatom Nitzschia closterium, the
      freshwater green alga Pseudokirchneriella subcapitata and two tropical Chlorella
      spp. Under control conditions (no copper), N. closterium and P. subcapitata grew
      better in the presence of the bacterial community. Sensitivity to copper
      (assessed as the concentration to inhibit the growth rate by 50% after 72-h
      (IC50)) was not significantly different for the axenic and non-axenic strains of
      N. closterium, P. subcapitata or for Chlorella sp. (PNG isolate). At pH 5.7, the
      axenic Chlorella sp. (NT isolate) had a 72-h IC50 of 46mugCuL(-1), while in the
      presence of bacteria the IC50 increased (i.e., sensitivity decreased) to
      208mugCuL(-1). However, when the bacterial status of both the operationally
      defined axenic and non-axenic cultures of N. closterium and Chlorella sp. (NT
      isolate) was investigated using polymerase chain reaction (PCR) amplification of
      16S rRNA followed by DNA fingerprinting using denaturing gradient gel
      electrophoresis (DGGE), it was found that bacteria were actually present in all
      the algal cultures, i.e. the axenic cultures were not truly bacteria-free. Based
      on sequence information, the bacteria present were nearly all identified as
      alphaproteobacteria, and a number of isolates had high similarity to bacteria
      previously identified as symbionts or species endophytically associated with
      marine organisms. The "axenic" cultures contained less bacterial phylotypes than
      the non-axenic cultures, and based on band-intensity, also contained less
      bacterial DNA. This supported the findings of few differences in copper
      sensitivity between strains, and suggests that standard microalgal toxicity tests
      probably inadvertently use non-axenic cultures in metal assessment.

PMID- 19101015
TI  - Oxidoreductase activity of Sorghum root exudates in a phenanthrene-contaminated
      environment.
AB  - The effect of the polycyclic aromatic hydrocarbon (PAH) phenanthrene on the
      enzymatic activity of root exudates of the phytoremediating plant Sorghum bicolor
      (L.) Moench was studied. Analysis of sorghum root exudates allowed us to reveal
      the activities of oxidase, peroxidase, and tyrosinase. The activities of these
      enzymes were progressive as the soil phenanthrene concentration increased. Using
      lyophilized samples, we found that as a result of the enzymatic activity of the
      root exudates, some of the PAHs and products of PAH degradation were oxidized in
      the reaction mixture supplemented with the mediating agents (ABTS or DL-DOPA) but
      that no oxidation was observed in the reaction mixtures without the mediators.
      The revealed enzymatic activity of the sorghum root exudates may indicate the
      involvement of the root-released oxidoreductases in rhizospheric degradation of
      PAHs and/or their derivatives. In addition, from the data obtained, the coupling
      of plant and microbial metabolisms of PAHs in the rhizosphere may be surmised.

PMID- 19101016
TI  - Variables to be considered when assessing the photocatalytic destruction of
      bacterial pathogens.
AB  - The current study sought to assess the importance of three common variables on
      the outcome of TiO(2) photocatalysis experiments with bacteria. Factors
      considered were (a) ability of test species to withstand osmotic pressure, (b)
      incubation period of agar plates used for colony counts following photocatalysis
      and (c) chemical nature of suspension medium used for bacteria and TiO(2).
      Staphylococcus aureus, Escherichia coli, Salmonella ser. Typhimurium and
      Pseudomonas aeruginosa were found to vary greatly in their ability to withstand
      osmotic pressure, raising the possibility that osmotic lysis may be contributing
      to loss of viability in some photocatalytic disinfection studies. Agar plate
      incubation time was also found to influence results, as bacteria treated with UV
      light only grew more slowly than those treated with a combination of UV and
      TiO(2.) The chemical nature of the suspension medium used was found to have a
      particularly pronounced effect upon results. Greatest antibacterial activity was
      detected when aqueous sodium chloride solution was utilised, with approximately 1
      x 10(6) CFU mL(-1)S. aureus being completely killed after 60 min. Moderate
      activity was observed when distilled water was employed with bacteria being
      killed after 2h and 30 min, and no antibacterial activity at all was detected
      when aqueous tryptone solution was used. Interestingly, the antibacterial
      activity of UV light on its own appeared to be very much reduced in experiments
      where aqueous sodium chloride was employed instead of distilled water.

PMID- 19101017
TI  - Characteristics of trihalomethane (THM) production and associated health risk
      assessment in swimming pool waters treated with different disinfection methods.
AB  - Swimming pool water must be treated to prevent infections caused by microbial
      pathogens. In Korea, the most commonly used disinfection methods include the
      application of chlorine, ozone/chlorine, and a technique that uses
      electrochemically generated mixed oxidants (EGMOs). The purpose of this study was
      to estimate the concentrations of total trihalomethanes (TTHMs) in indoor
      swimming pools adopting these disinfection methods, and to examine the
      correlations between the concentrations of THMs and TTHMs and other factors
      affecting the production of THMs. We also estimated the lifetime cancer risks
      associated with various exposure pathways by THMs in swimming pools. Water
      samples were collected from 183 indoor swimming pools in Seoul, Korea, and were
      analyzed for concentrations of each THM, TOC, and the amount of KMnO(4)
      consumption. The free chlorine residual and the pH of the pool water samples were
      also measured. The geometric mean concentrations of TTHMs in the swimming pool
      waters were 32.9+/-2.4 microg/L for chlorine, 23.3+/-2.2 microg/L for
      ozone/chlorine, and 58.2+/-1.7 microg/L for EGMO. The concentrations of THMs
      differed significantly among the three treatment methods, and the correlation
      between THMs and TTHMs and the other factors influencing THMs varied. The
      lifetime cancer risk estimation showed that, while risks from oral ingestion and
      dermal exposure to THMs are mostly less than 10(-6), which is the negligible risk
      level defined by the US EPA, however swimmers can be at the greater risk from
      inhalation exposure (7.77x10(-4)-1.36x10(-3)).

PMID- 19101018
TI  - Mapping the impact of climate change on surface recession of carbonate buildings
      in Europe.
AB  - Climate change is currently attracting interest at both research and policy
      levels. However, it is usually explored in terms of its effect on agriculture,
      water, industry, energy, transport and health and as yet has been insufficiently
      addressed as a factor threatening cultural heritage. Among the climate parameters
      critical to heritage conservation and expected to change in the future,
      precipitation plays an important role in surface recession of stone. The Lipfert
      function has been taken under consideration to quantify the annual surface
      recession of carbonate stone, due to the effects of clean rain, acid rain and dry
      deposition of pollutants. The present paper provides Europe-wide maps showing
      quantitative predictions of surface recession on carbonate stones for the 21st
      century, combining a modified Lipfert function with output from the Hadley global
      climate model. Chemical dissolution of carbonate stones, via the karst effect,
      will increase with future CO(2) concentrations, and will come to dominate over
      sulfur deposition and acid rain effects on monuments and buildings in both urban
      and rural areas. During the present century the rainfall contribution to surface
      recession is likely to have a small effect, while the increase in atmospheric
      CO(2) concentration is shown to be the main factor in increasing weathering via
      the karst effect.

PMID- 19101019
TI  - Concentrations and risk assessment of selected monoaromatic hydrocarbons in buses
      and bus stations of Hangzhou, China.
AB  - Air pollution surveys of ten selected monoaromatic hydrocarbons (MAHCs) were
      conducted in buses and bus stations in Hangzhou, China. The mean concentrations
      of MAHCs in the air of buses and bus stations were 95.9 and 36.5 microg/m(3),
      respectively, of which toluene was the highest in all the sampling sites. Mean
      concentrations of all MAHCs in buses were statistically higher than those nearby
      bus stations (p<0.05). MAHCs concentrations in buses largely depend on vehicle
      conditions (including vehicle type, fuel type, interior decoration, etc.) and
      traffic conditions (mainly traffic density). Among the investigated buses,
      microbuses had the highest MAHCs level, while electric buses had the lowest.
      Buses driven in downtown had the highest MAHCs level, followed by those in
      suburban areas and tourist areas. The mean concentration ratio of toluene to
      benzene was 2.1+/-0.9, indicating that vehicle emission was the dominant source
      of MAHCs. Interior decorations, such as painting and surface coating, could also
      contribute to the MAHCs in the buses. The mean lifetime carcinogenic risks for
      passengers and bus drivers were 1.11x10(-5) and 4.00x10(-5), respectively, which
      were way above the limit set by USEPA. The health risk caused by MAHCs in bus
      microenvironment should be cautioned.

PMID- 19101020
TI  - Study on the degradation of 2,4-dichlorophenoxyacetic acid (2,4-D) and 2-methyl-4
      chloro-phenoxyacetic sodium (MCPA sodium) in natural agriculture-soils of Fuzhou,
      China using capillary electrophoresis.
AB  - A new method of analyzing trace 2,4-Dichlorophenoxyacetic acid (2,4-D) and 2
      methy-4-chloro-lphenoxyacetic sodium (MCPA sodium) in soils by capillary
      electrophoresis (CE) has been developed in this study. The optimum analytical
      conditions including chemical component and concentration of buffer solution, pH,
      separation voltage and sample injection time were studied in detail. Under the
      optimum conditions, 2,4-D and MCPA sodium in soils can be speedy separated and
      determined within 20 min with detection limits of 0.15 microg/g (2,4-D) and 0.25
      microg/g (MCPA sodium) , a RSD (n=6)<5% and a recovery>89%. With the help of
      analytical method developed in this study, the degradations of 2,4-D and MCPA
      sodium in natural agriculture-soils of Fuzhou were studied. The experimental
      results indicated that the degradations of 2,4-D and MCPA sodium follow first
      order kinetics with degradation constants of 0.1509 day(-1) (2,4-D) and 0.2722
      day(-1) (MCPA sodium) respectively. The degradation half-life were calculated to
      be 4.6 days (2,4-D) and 2.6 days (MCPA sodium) at 27 degrees C, implied that 2,4
      D and MCPA sodium can be speedy degraded in natural agriculture-soils of Fuzhou,
      China.

PMID- 19101021
TI  - Analysis of environmental endocrine disrupting chemicals using the E-screen
      method and stir bar sorptive extraction in wastewater treatment plant effluents.
AB  - Endocrine disrupting chemicals (EDCs) have become a major issue in the field of
      environmental science due to their ability to interfere with the endocrine
      system. Recent studies show that surface water is contaminated with EDCs, many
      released from wastewater treatment plants (WWTP). This pilot study used
      biological (E-screen assay) and chemical (stir bar sorptive extraction-GC-MS)
      analyses to quantify estrogenic activity in effluent water samples from a
      municipal WWTP and in water samples of the recipient river, upstream and
      downstream of the plant. The E-screen assay was performed on samples after solid
      phase extraction (SPE) to determine total estrogenic activity; the presence of
      estrogenic substances can be evaluated by measuring the 17-beta-estradiol
      equivalency quantity (EEQ). Untreated samples were also assayed with an acute
      toxicity test (Vibrio fischeri) to study the correlation between toxicity and
      estrogenic disruption activity. Mean EEQs were 4.7 ng/L (+/-2.7 ng/L) upstream
      and 4.4 ng/L (+/-3.7 ng/L) downstream of the plant, and 11.1 ng/L (+/-11.7 ng/L)
      in the effluent. In general the WWTP effluent had little impact on estrogenicity
      nor on the concentration of EDCs in the river water. The samples upstream and
      downstream of the plant were non-toxic or weakly toxic (0<TU<0.9) while the
      effluent was weakly toxic or toxic (0.4<TU<7.6). Toxicity and estrogenic activity
      were not correlated. At most sites, industrial mimics, such as the alkylphenols
      and phthalates, were present in higher concentrations than natural hormones.
      Although the concentrations of the detected xenoestrogens were generally higher
      than those of the steroids, they accounted for only a small fraction of the EEQ
      because of their low estrogenic potency. The EEQs resulting from the E-screen
      assay and those calculated from the results of chemical analyses using estradiol
      equivalency factors were comparable for all samples and closely correlated.

PMID- 19101022
TI  - How nitrogen and sulphur addition, and a single drought event affect root
      phosphatase activity in Phalaris arundinacea.
AB  - Conservation and restoration of fens and fen meadows often aim to reduce soil
      nutrients, mainly nitrogen (N) and phosphorus (P). The biogeochemistry of P has
      received much attention as P-enrichment is expected to negatively impact on
      species diversity in wetlands. It is known that N, sulphur (S) and hydrological
      conditions affect the biogeochemistry of P, yet their interactive effects on P
      dynamics are largely unknown. Additionally, in Europe, climate change has been
      predicted to lead to increases in summer drought. We performed a greenhouse
      experiment to elucidate the interactive effects of N, S and a single drought
      event on the P-availability for Phalaris arundinacea. Additionally, the response
      of plant phosphatase activity to these factors was measured over the two year
      experimental period. In contrast to results from earlier experiments, our
      treatments hardly affected soil P-availability. This may be explained by the
      higher pH in our soils, hampering the formation of Fe-P or Fe-Al complexes.
      Addition of S, however, decreased the plants N:P ratio, indicating an effect of S
      on the N:P stoichiometry and an effect on the plant's P-demand. Phosphatase
      activity increased significantly after addition of S, but was not affected by the
      addition of N or a single drought event. Root phosphatase activity was also
      positively related to plant tissue N and P concentrations, plant N and P uptake,
      and plant aboveground biomass, suggesting that the phosphatase enzyme influences
      P-biogeochemistry. Our results demonstrated that it is difficult to predict the
      effects of wetland restoration, since the involved mechanisms are not fully
      understood. Short-term and long-term effects on root phosphatase activity may
      differ considerably. Additionally, the addition of S can lead to unexpected
      effects on the biogeochemistry of P. Our results showed that natural resource
      managers should be careful when restoring degraded fens or preventing desiccation
      of fen ecosystems.

PMID- 19101023
TI  - Respiratory syncytial virus neutralizing antibodies in cord blood, respiratory
      syncytial virus hospitalization, and recurrent wheeze.
AB  - BACKGROUND: Respiratory syncytial virus (RSV) hospitalization is associated with
      wheeze. OBJECTIVE: To examine the influence of maternally derived RSV
      neutralizing antibodies in cord blood on RSV hospitalization and recurrent wheeze
      in infancy. METHODS: Among children from the Danish National Birth Cohort, we
      selected a subcohort of 459 randomly selected children, 408 children with RSV
      hospitalization, 408 children with recurrent wheeze, and all 289 children who
      experienced both RSV hospitalization and recurrent wheeze. The influence of cord
      blood RSV neutralizing antibodies was examined as predictors for (1) RSV
      hospitalization, (2) RSV hospitalization after recurrent wheeze, (3) recurrent
      wheeze, and (4) recurrent wheeze after RSV hospitalization. RESULTS: Neutralizing
      antibody levels were inversely associated with RSV hospitalization in infants
      below 6 months of age (adjusted incidence rate ratio [IRR], 0.74; 95% CI, 0.62
      0.87), and also inversely associated with RSV hospitalization in infants with
      recurrent wheeze (IRR, 0.83; 0.71-0.97). In contrast, neutralizing antibody
      levels were directly associated with an increased risk of recurrent wheeze in
      infants below 6 months of age (IRR, 1.28; 1.04-1.57) and with an increased risk
      of recurrent wheeze after RSV hospitalization in infants below 6 months of age
      (IRR, 1.44; 1.10-1.90). CONCLUSION: Maternally derived RSV neutralizing
      antibodies protect infants against RSV hospitalization, and also when the infant
      has recurrent wheeze. However, high maternally derived RSV neutralizing antibody
      levels were associated with an increased risk of recurrent wheeze.

PMID- 19101024
TI  - Canine oocyte maturation in culture: significance of estrogen and EGF receptor
      gene expression in cumulus cells.
AB  - We examined the role of cumulus cells regarding in vitro maturation of canine
      oocytes, and investigated estrogen and epidermal growth factor (EGF) receptor
      gene expression and action on nuclear maturation. Canine cumulus-oocyte complexes
      (COC) were collected from anestrous and diestrous bitches; only COC with
      vitelline diameter >100 microm were used. In Experiment 1, expression of estrogen
      receptor (ER) alpha, ERbeta and EGF-receptor (EGF-R) were determined by reverse
      transcription-polymerase chain reaction (RT-PCR), using mRNA from the oocyte or
      cumulus cell. Transcripts for the ERbeta and EGF-R were detected in oocytes and
      cumulus cells, but no message was detected for ERalpha. In Experiment 2, intact
      COC and the denuded oocytes were cultured in TCM199 medium supplemented with
      various concentrations of estradiol-17beta (E(2); 0-10 microg/mL) or EGF (0-100
      ng/mL) for 72 h; nuclear maturation was then evaluated. In oocytes cultured
      within intact COC, the rate of germinal vesicle breakdown (GVBD) was higher in
      the 1 microg/mL E(2) supplemented group (P<0.05), and the rate of metaphase I
      (MI) was higher in the 10 ng/mL EGF supplemented group, than in the non
      supplemented group (P<0.05). However, supplementation of E(2) or EGF to denuded
      oocytes failed to promote nuclear maturation. In Experiment 3, intact COC were
      cultured in TCM199 supplemented with 1 microg/mL E(2), 10 ng/mL EGF, and 10%
      fetal bovine serum (FBS) for 72 h, and nuclear maturation was evaluated. There
      was no significant difference in the rate of metaphase II (MII) between the
      medium only, E(2)+EGF, and FBS supplement groups. When E(2) and EGF in
      combination with FBS were supplemented, the rate of MII was higher than in other
      groups (P<0.05). We inferred that cumulus cells were involved in mediating the
      stimulatory effects of E(2) and EGF on nuclear maturation of canine oocytes, and
      that E(2) and EGF in combination with FBS promoted the completion of oocyte
      meiotic maturation.

PMID- 19101026
TI  - Calcium and phosphate ion releasing composite: effect of pH on release and
      mechanical properties.
AB  - OBJECTIVES: Secondary caries and restoration fracture are the two main challenges
      facing tooth cavity restorations. The objective of this study was to develop a
      composite using tetracalcium phosphate (TTCP) fillers and whiskers to be stress
      bearing, and to be "smart" to increase the calcium (Ca) and phosphate (PO(4)) ion
      release at cariogenic pH. METHODS: TTCP was ball-milled to obtain four different
      particle sizes: 16.2, 2.4, 1.3, and 0.97 microm. Whiskers fused with nano-sized
      silica were combined with TTCP as fillers in a resin. Filler level mass fractions
      varied from 0 to 75%. Ca and PO(4) ion releases were measured vs. time at pH of
      7.4, 6, and 4. Composite mechanical properties were measured via three-point
      flexure before and after immersion in solutions at the three pH. RESULTS: TTCP
      composite without whiskers had flexural strength similar to a resin-modified
      glass ionomer (Vitremer) and previous Ca-PO(4) composites. With whiskers, the
      TTCP composite had a flexural strength (mean+/-S.D.; n=5) of (116+/-9)MPa,
      similar to (112+/-14)MPa of a stress-bearing, non-releasing hybrid composite
      (TPH) (p>0.1). The Ca release was (1.22+/-0.16)mmol/L at pH of 4, higher than
      (0.54+/-0.09) at pH of 6, and (0.22+/-0.06) at pH of 7.4 (p<0.05). PO(4) release
      was also dramatically increased at acidic pH. After immersion, the TTCP-whisker
      composite matched the strength of TPH at all three pH (p>0.1); both TTCP-whisker
      composite and TPH had strengths about threefold that of a releasing control.
      SIGNIFICANCE: The new TTCP-whisker composite was "smart" and increased the Ca and
      PO(4) release dramatically when the pH was reduced from neutral to a cariogenic
      pH of 4, when these ions are most needed to inhibit caries. Its strength was two-
      to threefold higher than previously known Ca-PO(4) composites and resin-modified
      glass ionomer. This composite may have the potential to provide the necessary
      combination of load-bearing and caries-inhibiting capabilities.

PMID- 19101025
TI  - Dissociating verbal and nonverbal audiovisual object processing.
AB  - This fMRI study investigates how audiovisual integration differs for verbal
      stimuli that can be matched at a phonological level and nonverbal stimuli that
      can be matched at a semantic level. Subjects were presented simultaneously with
      one visual and one auditory stimulus and were instructed to decide whether these
      stimuli referred to the same object or not. Verbal stimuli were simultaneously
      presented spoken and written object names, and nonverbal stimuli were photographs
      of objects simultaneously presented with naturally occurring object sounds.
      Stimulus differences were controlled by including two further conditions that
      paired photographs of objects with spoken words and object sounds with written
      words. Verbal matching, relative to all other conditions, increased activation in
      a region of the left superior temporal sulcus that has previously been associated
      with phonological processing. Nonverbal matching, relative to all other
      conditions, increased activation in a right fusiform region that has previously
      been associated with structural and conceptual object processing. Thus, we
      demonstrate how brain activation for audiovisual integration depends on the
      verbal content of the stimuli, even when stimulus and task processing differences
      are controlled.

PMID- 19101027
TI  - Measurement of the full-field polymerization shrinkage and depth of cure of
      dental composites using digital image correlation.
AB  - OBJECTIVES: The aim of this study was to measure the full-field polymerization
      shrinkage of dental composites using optical image correlation method. METHODS:
      Bar specimens of cross-section 4mm x 2mm and length 10mm approximately were light
      cured with two irradiances, 450 mW/cm(2) and 180 mW/cm(2), respectively. The
      curing light was generated with Optilux 501 (Kerr) and the two different
      irradiances were achieved by adjusting the distance between the light tip and the
      specimen. A single-camera 2D measuring system was used to record the deformation
      of the composite specimen for 30 min at a frequency of 0.1 Hz. The specimen
      surface under observation was sprayed with paint to produce sufficient contrast
      to allow tracking of individual points on the surface. The curing light was
      applied to one end of the specimen for 40s during which the painted surface was
      fully covered. After curing, the cover was removed immediately so that
      deformation of the painted surface could be recorded by the camera. The images
      were then analyzed with specialist software and the volumetric shrinkage
      determined along the beam length. RESULTS: A typical shrinkage strain field
      obtained on a specimen surface was highly non-uniform, even at positions of
      constant distance from the irradiation surface, indicating possible heterogeneity
      in material composition and shrinkage behavior in the composite. The maximum
      volumetric shrinkage strain of approximately 1.5% occurred at a subsurface
      distance of about 1mm, instead of at the irradiation surface. After reaching its
      peak value, the shrinkage strain then gradually decreased with increasing
      distance along the beam length, before leveling off to a value of approximately
      0.2% at a distance of 4-5mm. The maximum volumetric shrinkage obtained agreed
      well with the value of 1.6% reported by the manufacturer for the composite
      examined in this work. Using irradiance of 180 mW/cm(2) resulted in only slightly
      less polymerization shrinkage than using irradiance of 450 mW/cm(2).
      SIGNIFICANCE: Compared to the other measurement methods, the image correlation
      method is capable of producing full-field information about the polymerization
      shrinkage behavior of dental composites.

PMID- 19101028
TI  - Obstructive sleep apnoea and its cardiovascular consequences.
AB  - Obstructive sleep apnoea (OSA) is a common disorder in which repetitive apnoeas
      expose the cardiovascular system to cycles of hypoxia, exaggerated negative
      intrathoracic pressure, and arousals. These noxious stimuli can, in turn, depress
      myocardial contractility, activate the sympathetic nervous system, raise blood
      pressure, heart rate, and myocardial wall stress, depress parasympathetic
      activity, provoke oxidative stress and systemic inflammation, activate platelets,
      and impair vascular endothelial function. Epidemiological studies have shown
      significant independent associations between OSA and hypertension, coronary
      artery disease, arrhythmias, heart failure, and stroke. In randomised trials,
      treating OSA with continuous positive airway pressure lowered blood pressure,
      attenuated signs of early atherosclerosis, and, in patients with heart failure,
      improved cardiac function. Current data therefore suggest that OSA increases the
      risk of developing cardiovascular diseases, and that its treatment has the
      potential to diminish such risk. However, large-scale randomised trials are
      needed to determine, definitively, whether treating OSA improves cardiovascular
      outcomes.

PMID- 19101029
TI  - Skin diseases in Guiana dolphins (Sotalia guianensis) from the Paranagua estuary,
      Brazil: a possible indicator of a compromised marine environment.
AB  - We report on the presence of lobomycosis-like disease (LLD) and nodular skin
      disease (NSD) in a community of Guiana dolphins (Sotalia guianensis) inhabiting
      the biologically and chemically contaminated Paranagua estuary (Brazil) and on
      their absence in the community living in the cleaner Cananeia estuary. Prevalence
      rates of LLD and NSD were 3.9% and 12.6%, respectively, in 103 photo-identified
      (PI) dolphins from the Paranagua estuary in the period 2006-2007. Adults and
      calves were affected. Lobomycosis-like lesions may be extensive and form large
      plaques. Skin nodules were sometimes ulcerated and associated with cutaneous
      traumas suggesting that traumatic injuries may play a role in the pathogenesis of
      this condition. In two adult dolphins, NSD evoked the beginning of LLD. In 1996
      2007 none of the 200 PI Cananeia S. guianensis had LLD or NSD, a highly
      significant difference. Interestingly, these dolphins were reported to harbour
      relatively low concentrations of organochlorines. LLD and NSD are possibly
      indicators of environmental changes.

PMID- 19101030
TI  - The in vivo degradation of a ruthenium labelled polysaccharide-based hydrogel for
      bone tissue engineering.
AB  - In this paper we report a new method that permitted for the first time to
      selectively track a polysaccharide-based hydrogel on bone tissue explants,
      several weeks after its implantation. The hydrogel, which was developed for bone
      healing and tissue engineering, was labelled with a ruthenium complex and
      implanted into rabbit bone defects in order to investigate its in vivo
      degradation. 1, 2, 3 and 8 weeks after surgery, the bone explants were analyzed
      by synchrotron X-ray microfluorescence, infrared mapping spectroscopy, scanning
      electron microscopy, and optical microscopy after histological coloration. The
      results showed that the labelled polysaccharide-based hydrogel was likely to
      undergo phagocytosis that seemed to occur from the edge to the center of the
      implantation site up to at least the 8th week.

PMID- 19101031
TI  - A unified mathematical model for the prediction of controlled release from
      surface and bulk eroding polymer matrices.
AB  - A unified model has been developed to predict release not only from bulk eroding
      and surface eroding systems but also from matrices that transition from surface
      eroding to bulk eroding behavior during the course of degradation. This broad
      applicability is afforded by fundamental diffusion/reaction equations that can
      describe a wide variety of scenarios including hydration of and mass loss from a
      hydrolysable polymer matrix. Together, these equations naturally account for
      spatial distributions of polymer degradation rate. In this model paradigm, the
      theoretical minimal size required for a matrix to exhibit degradation under
      surface eroding conditions was calculated for various polymer types and then
      verified by empirical data from the literature. An additional set of equations
      accounts for dissolution- and/or degradation-based release, which are dependent
      upon hydration of the matrix and erosion of the polymer. To test the model's
      accuracy, predictions for agent egress were compared to experimental data from
      polyanhydride and polyorthoester implants that were postulated to undergo either
      dissolution-limited or degradation-controlled release. Because these predictions
      are calculated solely from readily attainable design parameters, it seems likely
      that this model could be used to guide the design controlled release formulations
      that produce a broad array of custom release profiles.

PMID- 19101032
TI  - Increased TLR4 expression in murine placentas after oral infection with
      periodontal pathogens.
AB  - Maternal periodontitis has emerged as a putative risk factor for preterm births
      in humans. The periodontitis-associated dental biofilm is thought to serve as an
      important source of oral bacteria and related virulence factors that
      hematogenously disseminate and affect the fetoplacental unit; however the
      underlying biological mechanisms are yet to be fully elucidated. This study
      hypothesized that an oral infection with the human periodontal pathogens
      Campylobacter rectus and Porphyromonas gingivalis is able to induce fetal growth
      restriction, placental inflammation and enhance Toll-like receptors type 4 (TLR4)
      expression in a murine pregnancy model. Female Balb/C mice (n = 40) were orally
      infected with C. rectus and/or P. gingivalis over a 16-week period and mated
      once/week. Pregnant mice were sacrificed at embryonic day (E) 16.5 and placentas
      were collected and analyzed for TLR4 mRNA levels and qualitative protein
      expression by real-time PCR and immunofluorescence. TLR4 mRNA expression was
      found to be increased in the C. rectus-infected group (1.98 +/- 0.886-fold
      difference, P < 0.01, ANOVA) compared to controls. Microscopic analysis of murine
      placentas showed enhanced immunofluorescence of TLR4 in trophoblasts, mainly in
      the placental labyrinth layer. Also, combined oral infection with C. rectus and
      P. gingivalis significantly reduced the overall fecundity compared to controls
      (16.7% vs. 75%, infected vs. non-infected mice respectively, P = 0.03, Kaplan
      Meier). The results supported an enhanced placental TLR4 expression after oral
      infection with periodontal pathogens. The TLR4 pathway has been implicated in the
      pathogenesis of preterm births; therefore the abnormal regulation of placental
      TLR4 may give new insights into how maternal periodontitis and periodontal
      pathogens might be linked to placental inflammation and preterm birth
      pathogenesis.

PMID- 19101033
TI  - Distribution and genesis of the RFRP-producing neurons in the rat brain:
      comparison with melanin-concentrating hormone- and hypocretin-containing neurons.
AB  - Prepro-RFRP-containing neurons have recently been described in the mammalian
      brain. These neurons are only found in the tuberal hypothalamus. In this work, we
      have provided a detailed analysis of the distribution of cells expressing the
      RFRP mRNA, and found them in seven anatomical structures of the tuberal
      hypothalamus. No co-expression with melanin-concentrating hormone (MCH) or
      hypocretin (Hcrt), that are also described in neurons of the tuberal
      hypothalamus, was observed. Using the BrdU method, we found that all RFRP cell
      bodies are generated between E13 and E14. Thus, RFRP neurons form a specific cell
      population with a complex distribution pattern in the tuberal hypothalamus.
      However, they are generated in one peak. These observations are discussed with
      data concerning the distribution and genesis of the MCH and Hcrt cell populations
      that are also distributed in the tuberal hypothalamus.

PMID- 19101034
TI  - DNA repair gene XPD and XRCC1 polymorphisms and the risk of childhood acute
      lymphoblastic leukemia.
AB  - Polymorphisms have been identified in several DNA repair genes. These
      polymorphisms may effect DNA repair capacity and modulate cancer susceptibility.
      In this study, we aimed to determine the four polymorphisms in two DNA repair
      genes, xeroderma pigmentosum complementation group D (XPD) and X-ray repair cross
      complementing group 1 (XRCC1), in a sample of Turkish patients with childhood
      acute lymphoblastic leukemia (ALL), and evaluate their association with childhood
      ALL development. We used polymerase chain reaction (PCR) and restriction fragment
      length polymorphism (RFLP), to analyze XPD Asp312Asn, XPD Lys751Gln, XRCC1
      Arg194Trp, and XRCC1 Arg399Gln polymorphisms in 70 patients with childhood ALL
      and in 75 disease-free controls, who were of a similar age. No significant
      differences were observed among the study groups with regard to the XPD codon
      312, XPD codon 751, XRCC1 codon 194, and XRCC1 codon 399 polymorphisms. However,
      the combined XRCC1 Arg194Trp/Trp194Trp variant genotypes were associated with
      increased risk for ALL in females (OR=5.47; 95% CI=1.49-20.10; p=0.008). This
      finding indicates that females carrying XRCC1 194Trp allele are at increased risk
      of developing childhood ALL. These results suggest that the risk of childhood ALL
      may be associated with DNA repair mechanisms, and understanding these mechanisms
      will help identify individuals at increased risk of developing childhood ALL, and
      also should be lead to improved treatment of ALL.

PMID- 19101035
TI  - Prevalence of Q fever in domestic animals with reproductive disorders.
AB  - The occurrence of Coxiella burnetii in animals with reproductive disorders was
      studied. A total of 920 samples (genital and faecal swabs, milk, urine and serum)
      were collected from cows (88), buffaloes (33), sheep (43) and goats (53) with a
      history of reproductive disorders and screened for C. burnetii by a PCR assay
      targeting the repetitive transposon-like region of C. burnetii (trans-PCR), real
      time PCR, indirect immunofluorescence assay (IFA), enzyme-linked immunosorbent
      assay (ELISA) and isolation method. The overall prevalence of Q fever in animals
      with the history of reproductive disorders turned out to be 13.82%. The species
      wise prevalence of Q fever among animals was observed to be 12.78% in cattle,
      16.66% in buffaloes, 11.04% in sheep and 6.13% in goats. In comparison to IFA,
      the highest sensitivity (85.18%) was shown by both PCR assays followed by ELISA
      (74.07%) and isolation method (14.81%) whereas, isolation method was the most
      specific (100%) followed by both PCR assays (99.47%) and ELISA (98.44%). The high
      excretion rate of pathogen particularly in milk observed in the study posses a
      potential public health threat from infected animals.

PMID- 19101036
TI  - Interpersonal partner violence and women in the United States: an overview of
      prevalence rates, psychiatric correlates and consequences and barriers to help
      seeking.

PMID- 19101037
TI  - Occurrence and fate of pharmaceutical products and by-products, from resource to
      drinking water.
AB  - Among all emerging substances in water, pharmaceutical products (PPs) and
      residues are a lot of concern. These last two years, the number of studies has
      increased drastically, however much less for water resources and drinking water
      than for wastewater. This literature review based on recent works, deals with
      water resources (surface or groundwater), focusing on characteristics, occurrence
      and fate of numerous PPs studied, and drinking water including water quality.
      Through this review, it appears that the pharmaceutical risk must be considered
      even in drinking water where concentrations are very low. Moreover, there is a
      lack of research for by-products (metabolites and transformation products)
      characterization, occurrence and fate in all water types and especially in
      drinking water.

PMID- 19101038
TI  - Understanding medication non-adherence in bipolar disorders using a Necessity
      Concerns Framework.
AB  - BACKGROUND: Medication non-adherence is a major problem in patients with severe
      mental disorders and is associated with poor clinical outcomes and high resource
      utilization. This study examined the utility of the Necessity-Concerns Framework
      for understanding patient attitudes towards and levels of adherence with
      medications prescribed for bipolar disorders. METHOD: A convenience sample of 223
      individuals currently prescribed medication for bipolar disorders, recruited by
      advertisement in a Manic Depression Fellowship newsletter, completed the Beliefs
      about Medication Questionnaire and the Medication Adherence Report Scale.
      RESULTS: Low adherence was reported by 30% (n=64) and was predicted by greater
      doubts about personal need for treatment (OR=.50; 95% CI: .31-.82) and stronger
      concerns about potential negative effects (OR=2.00; 95% CI: 1.20-3.34). These
      predictors were independent of current mood state, illness and demographic
      characteristics. LIMITATIONS: Participants were a potentially biased sample of
      volunteers who had been recruited through a patient organisation newsletter.
      However, clinical characteristics and adherence rates in this study were similar
      to those reported in other studies conducted in Europe and the USA. CONCLUSIONS:
      The Necessity-Concerns Framework is a useful theoretical model for understanding
      key attitudes towards medication in bipolar disorders. Interventions to
      facilitate adherence should elicit and address patients' beliefs about
      medication.

PMID- 19101039
TI  - Leukocyte-derived and endogenous matrix metalloproteinases in the lamellae of
      horses with naturally acquired and experimentally induced laminitis.
AB  - RATIONALE: Inflammation and dysregulation of endogenous matrix metalloproteinase
      (MMP) production are implicated in the development of equine laminitis. In this
      study, we examine quantitative relationships among levels of leukocyte-derived
      proMMP-9 and MMP-9, lamellar proMMP-2 and MMP-2, and expression of proMMP-2
      processing enzymes, MT1-MMP/PACE4, as steps towards determining whether
      inflammation and dysregulation of endogenous MMP production are independent or co
      dependent processes. ANIMALS: Archived samples of lamellae from horses with
      naturally acquired laminitis (n = 12), and from horses administered a pro
      laminitic gastric bolus of starch gruel were used, the latter horses falling into
      two groups: (i) responders (CHO-R, n = 7), which developed Obel grade 3-lameness
      and (ii) non-responders (CHO-NR, n = 4), which did not become lame. METHODS:
      Lamellar tissue extracts were analyzed by gelatin zymography to determine
      gelatinase content and by a myeloperoxidase ELISA to quantify relative
      monocyte/neutrophil content in the tissue. Real-time PCR was employed to measure
      gene expression of MT1-MMP and PACE4. RESULTS AND CONCLUSIONS: Extracts of
      lamellae from control horses, CHO-NR and horses with chronic (non-aggravated)
      laminitis had similarly low levels of pro and processed MMP-9 and MMP-2. In
      contrast, proMMP-9 was significantly elevated in extracts of lamellae from CHO-R
      and horses with naturally acquired acute and aggravated chronic laminitis.
      Lamellar MMP-2 was also increased significantly in the CHO-R and aggravated
      chronic laminitis groups, although not in the horses with naturally acquired
      acute laminitis. Concentrations of proMMP-9 correlated directly with
      myeloperoxidase content in lamellar extracts, suggesting production/induction by
      inflammatory leukocytes. In contrast, concentrations of proMMP-2 and MMP-2 were
      unrelated to concentrations of myeloperoxidase or proMMP-9 suggesting that
      leukocyte infiltration and dysregulation of endogenous MMP-2 are independent
      processes most likely with distinct inducers. Neither MT1-MMP nor PACE4 gene
      expression was elevated relative to controls in any group; this is discussed with
      respect to proMMP-2 processing in disease. In addition, variability in relative
      concentrations of lamellar MMPs observed among horses with Obel grade 3-lameness
      is discussed in the context of laminitis risk assessment and disease outcome.

PMID- 19101041
TI  - PHACES syndrome: a review.
AB  - Large, segmental, cervicofacial hemangiomas are often associated with anomalies
      of intracranial, cardiovascular, and ophthalmic systems as well as ventral
      development.

PMID- 19101040
TI  - Antioxidant enzyme dysfunction in monocytes and CSF of Hispanic women with HIV
      associated cognitive impairment.
AB  - HIV-associated cognitive neurological disorders (HAND) prevail in the
      antiretroviral therapy era. Proteomics analysis of CSF revealed expression of
      Cu/Zn superoxide dismutase (Cu/Zn SOD) in Hispanic women with cognitive
      impairment (CI). We tested the hypothesis that there is reduced capacity of
      antioxidant enzymes in CI by measures of expression and activity of Cu/Zn SOD,
      catalase, and Se-glutathione peroxidase in HAND. Our results showed that the
      function of these antioxidants was decreased in the CSF and monocytes of women
      with CI. These findings have important implications regarding their possible
      contribution to oxidative stress and in the diagnosis and therapy for HAND.

PMID- 19101042
TI  - Comparison of nasal region dimensions in bilateral choanal atresia patients and
      normal controls: a computed tomographic analysis with clinical implications.
AB  - OBJECTIVE: To determine if any difference exists between a set of nasal dimension
      measurements in choanal atresia patients and in a control group. METHODS: A
      retrospective study was undertaken to define the variation of values for a series
      of nasal dimension measurements through axial computed tomography in 9 patients
      with bilateral choanal atresia and compare the same dimensions with a control
      group 104 patients of similar gender and age distribution. The statistical
      significance of the differences in these dimensions was examined. RESULTS: Nine
      of 17 variables showed a significant difference between normal and choanal
      atresia group. The result showed that the growth of the nasal complex can be
      influenced by nasal obstruction. CONCLUSION: These findings might serve in
      understanding the differential growth patterns of nasal structures in the face of
      the nasal breathing obstruction. Computed tomography is valuable in defining the
      exact anatomical extent of the disease and also in preoperative evaluation of the
      patient.

PMID- 19101043
TI  - The expression of NOB1 in spiral ganglion cells of guinea pig.
AB  - OBJECTIVE: NOB1 was a transcription-associated protein, consisting of one zinc
      ribbon domain. This study aimed to investigate the NOB1 expression in spiral
      ganglion cells of normal guinea pigs and deaf ones. METHODS: Twelve guinea pigs
      were randomized equally into experimental group and control group. In
      experimental group, guinea pigs received a single intramuscular injection of
      gentamicin, while the control group was treated with physiological saline.
      Auditory brainstem responses (ABR) test was performed before and 10 days after
      injection, respectively. Guinea pigs of both groups were sacrificed and temporal
      bones were removed. The expression of NOB1 in the spiral ganglion was evaluated
      by immunohistochemistry. RESULTS: NOB1 staining was found expressed in spiral
      ganglion cells from the basal turn to the apical turn of the cochlea. The
      expression of NOB1 was found significantly stronger in spiral ganglion cells of
      deaf guinea pigs as compared with that in normal ones. CONCLUSIONS: The NOB1 was
      presented in spiral ganglions cells of the guinea pig and might play a role in
      hearing transduction.

PMID- 19101044
TI  - Vestibular impairments pre- and post-cochlear implant in children.
AB  - OBJECTIVES: Determine prevalence and types of vestibular impairments in
      sensorineural hearing loss (SNHL) in a large population of pediatric candidates
      for cochlear implants. Evaluate impact of cochlear implants on vestibular
      function. STUDY DESIGN: Retrospective and prospective study. METHODS: Children
      with profound SNHL (n=224) underwent complete vestibular testing (clinical
      vestibular examination, bicaloric test, earth vertical axis rotation, off
      vertical axis rotation and vestibular evoked myogenic potentials) before cochlear
      implant. Changes in vestibular responses were measured after implants in 89 of
      these patients. RESULTS: In the SNHL population only 50% had normal bilateral
      vestibular function, while 20% had bilateral complete areflexia, 22.5% partial
      asymmetrical hypoexcitability and 7.5% partial symmetrical hypoexcitability. In
      the 71/89 follow-up patients showing vestibular responses prior to implant, 51
      (71%) had changes in vestibular function including 7 (10%) who acquired
      ipsilateral areflexia. Others developed ipsilateral hypo- or hyperexcitability.
      Vestibular modifications occurred during the 3 months after surgery and were not
      clearly associated with clinical signs except for ipsilateral areflexia cases. In
      long-term follow-up, two of the 7 patients with ipsilateral areflexia partially
      recovered vestibular function. CONCLUSION: Since half of pediatric cochlear
      implant candidates have vestibular deficits and 51% of implants induce
      modifications of existing vestibular function, each implant should be preceded by
      canal and otolith functional tests to assure that the least functional vestibule
      is implanted. The tests provide baselines for follow-up monitoring of subsequent
      losses and recovery. This could be easily implemented with a clinical vestibular
      examination including the head thrust test associated with a bicaloric test and
      vestibular-evoked-myogenic-potentials.

PMID- 19101045
TI  - Effect of ototopical ciprofloxacin-dexamethasone on myringotomy in a rat model.
AB  - OBJECTIVE: To examine the potential of ototopical ciprofloxacin-dexamethasone
      (CDX) to delay the closure of myringotomy perforation and to evaluate its effect
      on inflammation. STUDY DESIGN: Prospective, randomized, and controlled. METHODS:
      Effusion is obtained in the right middle ear of 24 rats by blocking
      nasopharyngeal opening of eustachian tube by fibrin glue. Left middle ears of 30
      rats remained healthy. Animals were randomly classified into three groups; each
      containing eight right ears with effusion and 10 rats with healthy left ear.
      Bilateral myringotomy was applied to all rats and randomly divided into three
      groups. First group received CDX, second group received serum physiologic (SF)
      for 14 days. Third group served as control. Otomicroscopy was performed by days
      7, 14 and 28 to assess wound healing. On day of 28, all animals were humanly
      euthanized in order to pathological examination of the tympanic bullas. RESULT:
      CDX group showed lesser perforation closure ratios both in healthy and diseased
      ears. Inflammation was found to be lesser at CDX group in comparison to other
      groups. CONCLUSION: Closure of the myringotomy perforation can be modulated by
      ototopical CDX treatment. This delaying of wound healing may be attributed to
      antiinflammatory action of dexamethasone.

PMID- 19101046
TI  - A new tool measuring health-related quality of life (HRQOL): the effects of
      musculoskeletal pain in a group of older Turkish people.
AB  - The aims of this study were (1) to show the effects of musculoskeletal pain on
      health-related quality of life (HRQOL) and (2) to look at gender differences in
      this field in elderly people living in Turkey. Subjects were 900 men and women
      (65 years of age or above), with a mean of 70.93+/-5.6 years. The centers for
      disease control (CDC) HRQOL-4 survey tool was used to measure HRQOL of the
      subjects. A visual analog scale (VAS) was used to determine pain intensity. The
      subjects were also asked to indicate sites where they experienced pain in their
      body. Of the subjects, 72.1% reported musculoskeletal pain. The prevalence of
      pain was higher among women (85.5%) than men (61.8%). Pain of lower extremities
      was the most common in both sexes. Whereas the majority of the subjects with
      musculoskeletal pain reported fair-poor self-rated health, those without pain
      reported excellent-very good-good health. Compared with subjects who did not
      report pain, those with pain had increased the number of physically and mentally
      unhealthy days in the previous 30 days (p=0.0001). The investigators concluded
      that musculoskeletal pain interfered negatively with HRQOL, increasing the number
      of unhealthy days and decreasing physical and mental performance in the elderly
      participants.

PMID- 19101047
TI  - Adverse local reactions to the use of hydrophilic sheaths for radial artery
      canulation.
AB  - There have been reports of local sterile inflammatory reactions with the use of
      Cook hydrophilic-coated sheaths (HCS) for transradial coronary
      angiography/intervention. Our aim was to gauge the extent of radial artery access
      site complications following radial artery canulation and to compare the
      incidence of such complications with HCS versus non-coated sheaths in our
      hospital. We undertook a retrospective questionnaire-based postal study,
      receiving replies from 1283 patients who had transradial coronary
      angiography/percutaneous coronary intervention in our institution between Feb
      2005 and Oct 2006. HCS had been used in 856 of these patients. Patients reported
      adverse local reactions at the access site in 12.9% of cases, including pain
      (57.2%), swelling (27.7%) and non-specific sensory abnormalities (13.2%). A total
      of 5.0% of patients sought medical help for their problem, mainly (78.1%) from
      their general practitioner. The use of a HCS compared to a non-coated sheath was
      associated with a significant excess of patient-reported adverse reactions (14.6%
      vs. 9.6%, p=0.015). A logistic regression analysis confirmed that the use of a
      hydrophilic sheath (OR 1.5, (1.05-2.26)) and female gender (OR 1.9, (1.4-2.8)),
      were independent predictors of self-reported adverse outcomes after controlling
      for possible confounders.

PMID- 19101048
TI  - Angiotensin converting-enzyme inhibitors and candesartan have no effects on
      atrial fibrillation after cardiac surgery: comment on: Mehmet Ozaydin et al.
      "Effect of renin-angiotensin aldosterone system blockers on postoperative atrial
      fibrillation".
AB  - The manuscript is a "Letter to the Editor" concerning the paper: "Ozaydin M, Dede
      O, Varol E, et al. Effect of renin-angiotensin aldosteron system blockers on
      postoperative atrial fibrillation. Int J Cardiol 2008; 127: 362-367".

PMID- 19101049
TI  - Pulmonary hypertension in systemic sclerosis determines cardiac autonomic
      dysfunction assessed by heart rate turbulence.
AB  - There is limited data on heart rate turbulence (HRT) in systemic sclerosis (SSc)
      patients, potentially threatened with cardiac autonomic dysfunction. We performed
      24-hour Holter monitoring for HRT assessment in 45 patients with SSc and 30
      healthy controls. Abnormal HRT defined as turbulence onset (TO) >or=0.0% and/or
      turbulence slope (TS)<or=2.5 ms/RR was found in 19 (42%) of SSc patients while
      not in controls. HRT was significantly impaired in SSc group, as compared to
      controls: a median of TO was higher (-0.13 vs. -2.45%, p=0.0001), and a median of
      TS was lower (6.90 vs. 13.21 ms/RR, p=0.0003), respectively. Multivariate
      analysis showed that abnormal HRT in SSc was significantly influenced by
      pulmonary hypertension (PH) (OR 6.1, 1.1-48.6; p=0.049) and older age (OR 1.8,
      95%CI 1.1-3.5; p=0.03). In conclusion, HRT assessment indicates a frequent
      impairment of cardiac autonomic nervous system in SSc patients. Moreover, older
      age in these patients and especially PH are independent significant predictors of
      cardiac autonomic dysfunction.

PMID- 19101050
TI  - Characterisation of isoform-specific tryptic peptides of rat cardiac myosin heavy
      chains using automated liquid chromatography-matrix assisted laser desorption
      ionisation (LC-MALDI) mass spectrometry.
AB  - Proteomics investigations using 2-dimensional electrophoresis (2-DE) cannot
      resolve the entire cardiac proteome because some proteins, including myosin heavy
      chains (MyHC), are insoluble in the buffers required for isoelectric focusing.
      Here, we report an automated mass spectrometry (MS) method complementary to 2-DE
      and capable of yielding important additional information. Rat myocardium was
      homogenised in standard lysis solution and centrifuged to produce a supernatant
      fraction, suitable for 2-DE. The pelleted fraction, which is normally discarded,
      was used for the current analysis. Proteins were digested with trypsin and the
      peptides fractionated by HPLC. Automated spotting of eluent fractions onto 384
      well target plates and matrix-assisted laser desorption tandem time of flight
      (MALDI-ToF/ToF) MS were directed by dedicated software. Peptide ions were
      fragmented by collision-induced dissociation and the MS/MS spectra searched
      against the NCBI database using Mascot. This approach confidently identified 13
      tryptic peptides specific to cardiac alpha-MyHC and 4 specific to beta-MyHC,
      which can be used to differentiate these highly homologous protein isoforms in
      future quantitative MS analyses.

PMID- 19101051
TI  - Correlation of NT-proBNP with diastolic left ventricular function in elderly
      patients with ischemic stroke.
AB  - We tested the hypothesis that, in elderly survivors of ischemic stroke, high NT
      proBNP levels are related with frequent diastolic dysfunction. We prospectively
      measured NT-proBNP, left ventricular ejection fraction (LVEF) and echographic
      parameters of diastolic function in 55 elderly consecutive patients, 6.8+/-2.6
      days after acute ischemic stroke. We found that all the patients had systolic or
      diastolic dysfunction (14 had LVEF<50%, 26 mild diastolic dysfunction+LVEF > or =
      50%, and 15 moderate or severe diastolic dysfunction+LVEF > or = 50%). The most
      powerful predictors of NT-proBNP were LVEF (R=0.38, p=0.004) and ratio of mitral
      E to the early diastolic velocity of the mitral annulus:E/E'(R=0.34, p=0.01).

PMID- 19101052
TI  - Seroprevalence and risk factors associated with seropositivity in sows from 67
      herds in north-west Germany infected with Mycoplasma hyopneumoniae.
AB  - Risk factors for the spread of Mycoplasma hyopneumoniae in sows have not been
      studied although vertical transmission from sows to their offspring is considered
      a significant risk factor in the development of enzootic pneumonia in growers and
      finishers. Seropositivity for M. hyopneumoniae in sows, as assessed by commercial
      ELISA, is a possible indicator of infection pressure among sows. The objective of
      this study was to estimate seroprevalence and associated risk factors of a sow
      being seropositive for M. hyopneumoniae. A cross-sectional study was carried out
      in 2578 sows from 67 herds in north-west Germany. Data concerning general herd
      characteristics, acclimatisation practices, indoor and outside contacts, as well
      as data describing the immediate local environment were collected during a herd
      visit via questionnaire. Blood samples were seropositive in 65% of the 2578 sows,
      and all herds had >/=14% seropositive sows. Data analysis was performed in two
      steps. First, univariate analysis of predictor variables for the risk of a sow
      being seropositive for M. hyopneumoniae was performed using chi-square test.
      Secondly, all variables associated with the risk of a sow being seropositive
      (P</=0.25) were included in a multivariate model using a generalised linear
      model. The risk of a sow being seropositive for M. hyopneumoniae was increased in
      herds with two- or three-site production (OR 1.50), when piglets were not
      vaccinated against M. hyopneumoniae (OR 1.81), in herds with a 2-week farrowing
      intervals (OR 1.84) and in herds without all-in/all-out management of the
      farrowing units (OR 1.37). The lack of an acclimatisation period for replacement
      boars was also associated with the risk of a sow being seropositive (OR 2.10).
      The results indicate that M. hyopneumoniae seropositivity is common in sows in
      north-west Germany and is influenced by various management factors. It is
      recommended that evaluation of sow herd management should be included in any
      strategic health plan to control M. hyopneumoniae infection.

PMID- 19101053
TI  - Morphological changes of Vibrio parahaemolyticus under cold and starvation
      stresses.
AB  - This study addresses morphological changes of Vibrio parahaemolyticus cells
      during the initial period of stress. Drastic changes occurred in cells under
      starvation with/without concomitant cold treatment for one to a few days. Under
      carbon starvation, rod-shaped cells became coccoid by reductive division, which
      was influenced by glucose/amino acid in the culture medium. Under concomitant
      cold and carbon starvation, cells entered the viable but nonculturable state and
      their shape changed from rod-like to coccoid with waning-shape and various
      aberrantly intermediates, such as club-shaped, budding, club-shaped with budding,
      dumbbell-shaped and rabbit-ear-like-shaped. Electron microscopy revealed
      characteristic features in the cells that were concomitantly stressed with cold
      and starved, such as densely stained peripheral part and lightly stained central
      part of cytoplasm, and a thick peptidoglycan cell wall in the temperature
      upshifted cells. The expression of cytoskeleton genes, mreB, minE and ftsZ, was
      determined in a real-time quantitative reverse transcription-polymerase chain
      reaction, and results revealed a substantial decline in expression in cells under
      starvation (to 0.25 to 0.64 times that of the control) in the first 2 to 3 h, and
      a rapid upregulated expression in recovering cells. Alteration of the morphology
      of cells under such stresses may be associated with the expression of these
      cytoskeleton genes. This work demonstrates the uniqueness of concomitant cold and
      starvation treatment in V. parahaemolyticus. The details of the morphological
      changes may facilitate understanding of stress adaptation in bacteria.

PMID- 19101054
TI  - Serum phosphate levels and the risk of cardiovascular disease and metabolic
      syndrome: a double-edged sword.
AB  - This study was performed to evaluate the relationship between serum phosphate
      levels and cardiovascular risk factors and metabolic syndrome components in a
      cross-sectional survey. Plasma phosphate was measured by immunoturbidimetry in
      46,798 subjects over 20 years of age with an estimated GFR>or=60 mL/(min 1.73
      m(2)) who participated in a health-check survey at the Kangbuk Samsung Hospital
      in South Korea. The median plasma phosphate level was 3.49+/-0.44 mg/dL and the
      mean estimated GFR was 77.46+/-8.51 mL/(min 1.73 m(2)). We found that serum
      phosphate levels had a positive correlation with total cholesterol, HDL-C,
      lipoprotein a, apolipoprotein A1, calcium, and albumin. In addition, serum
      phosphate levels had a negative correlation with age, body mass index, uric acid,
      fasting glucose, insulin, HOMA-IR, HS-CRP, triglyceride levels, systolic blood
      pressure, diastolic blood pressure, and waist circumference (P<0.001). In
      conclusion, we found that a high phosphate level is correlated with
      cardiovascular disease while a lower phosphate level is correlated with metabolic
      syndrome. Serum phosphate levels that were too high or too low correlated with
      cardiovascular risk factors and elements of metabolic syndrome, respectively,
      showing that it may be important to maintain an appropriate level of phosphate
      for the prevention of cardiovascular events and metabolic syndrome.

PMID- 19101055
TI  - Methylation and deamination of CpGs generate p53-binding sites on a genomic
      scale.
AB  - The formation of transcription-factor-binding sites is an important evolutionary
      process. Here, we show that methylation and deamination of CpG dinucleotides
      generate in vivo p53-binding sites in numerous Alu elements and in non-repetitive
      DNA in a species-specific manner. In light of this, we propose that the
      deamination of methylated CpGs constitutes a universal mechanism for de novo
      generation of various transcription-factor-binding sites in Alus.

PMID- 19101056
TI  - n-Gram characterization of genomic islands in bacterial genomes.
AB  - The paper presents a novel, n-gram-based method for analysis of bacterial genome
      segments known as genomic islands (GIs). Identification of GIs in bacterial
      genomes is an important task since many of them represent inserts that may
      contribute to bacterial evolution and pathogenesis. In order to characterize and
      distinguish GIs from rest of the genome, binary classification of islands based
      on n-gram frequency distribution have been performed. It consists of testing the
      agreement of islands n-gram frequency distributions with the complete genome and
      backbone sequence. In addition, a statistic based on the maximal order Markov
      model is used to identify significantly overrepresented and underrepresented n
      grams in islands. The results may be used as a basis for Zipf-like analysis
      suggesting that some of the n-grams are overrepresented in a subset of islands
      and underrepresented in the backbone, or vice versa, thus complementing the
      binary classification. The method is applied to strain-specific regions in the
      Escherichia coli O157:H7 EDL933 genome (O-islands), resulting in two groups of O
      islands with different n-gram characteristics. It refines a characterization
      based on other compositional features such as G+C content and codon usage, and
      may help in identification of GIs, and also in research and development of
      adequate drugs targeting virulence genes in them.

PMID- 19101057
TI  - The paradoxical spread of a new Y chromosome - a novel explanation.
AB  - Hybrid zones provide one of the more prickly challenges to the cherished
      biological species concept, which is based on reproductive isolation between
      species, because some hybrid zones occur in areas where recognised species come
      together and mate to produce viable progeny. By contrast, hybrid zones have
      repeatedly provided outstanding material for the study of evolution: they allow
      us to study ecological and genomic differences between recently diverged taxa;
      and they bring into sharp focus the interplay between migration, selection,
      recombination and drift. A new theoretical analysis now demonstrates that hybrid
      zone dynamics provide a counterintuitive explanation for how a new chromosomal
      sex-determination system can evolve and spread across the landscape, displacing
      the ancestral system, even though it would be eliminated by natural selection in
      a single isolated population. This work thus provides a provocative resolution to
      a conundrum that has puzzled cytogeneticists and evolutionary biologists for
      years.

PMID- 19101058
TI  - Coalescent genealogy samplers: windows into population history.
AB  - Coalescent genealogy samplers attempt to estimate past qualities of a population,
      such as its size, growth rate, patterns of gene flow or time of divergence from
      another population, based on samples of molecular data. Genealogy samplers are
      increasingly popular because of their potential to disentangle complex population
      histories. In the last decade they have been widely applied to systems ranging
      from humans to viruses. Findings include detection of unexpected reproductive
      inequality in fish, new estimates of historical whale abundance, exoneration of
      humans for the prehistoric decline of bison and inference of a selective sweep on
      the human Y chromosome. This review summarizes available genealogy-sampler
      software, including data requirements and limitations on the use of each program.

PMID- 19101059
TI  - A regional system of stroke care provides thrombolytic outcomes comparable with
      the NINDS stroke trial.
AB  - STUDY OBJECTIVE: Administration of tissue plasminogen activator (tPA) for acute
      ischemic stroke remains controversial in community practice. Well-organized
      hierarchic systems of acute stroke care have been proposed to link community
      hospitals to comprehensive stroke centers. We report safety and functional
      outcomes in patients treated with tPA in our regional emergency stroke network
      and compare them with results reported from the trial conducted by the National
      Institute of Neurological Disorders and Stroke (NINDS). METHODS: Through a
      statewide communications and transport network, our brain attack center gives
      emergency medicine staff in the state and surrounding area immediate access to
      stroke specialists. The team provides consultation about the administration of
      tPA for ischemic stroke, using the NINDS protocol. Consultations, treatment, and
      outcomes are documented in our database. RESULTS: From 1996 to 2005, the brain
      attack center completed 2,670 consultations and diagnosed 1,788 patients with
      ischemic stroke. Two hundred forty patients (9% of all consultations; 13.4% of
      those with acute ischemic stroke) received tPA. Percentages of patients with
      symptomatic intracranial hemorrhage and 3-month modified Rankin scale scores less
      than or equal to 1, compared with those in the NINDS trial, were as follows: 3.3%
      versus 6.4% and 53% versus 43% (P=.04). Mortality rates were 13% (network) versus
      17% (NINDS). CONCLUSION: During a 9-year period, an emergency medicine network
      with stroke consultants achieved patient outcomes comparable to those reported
      from the NINDS trial. These results indicate that the NINDS tPA protocol is
      applicable to community practice, with the support of a university-based brain
      attack center.

PMID- 19101060
TI  - Pediatric fatalities associated with over the counter (nonprescription) cough and
      cold medications.
AB  - STUDY OBJECTIVE: The use of nonprescription cough and cold medicines is
      widespread, but their use has been sporadically associated with severe toxicity
      and death. We evaluate the role of these medications in pediatric fatalities and
      identified factors that contributed to the death. METHODS: Fatalities that
      involved a child younger than 12 years and mentioned a cough and cold ingredient
      were obtained from 5 sources. An independent panel of 8 experts (pediatrics,
      pediatric critical care, pediatric toxicology, clinical toxicology, forensic
      toxicology, forensic pathology) used explicit definitions to assess the causal
      relationship between medication ingestion and death. Contributing factors were
      identified. RESULTS: Of 189 cases included, 118 were judged possibly, likely, or
      definitely related to a cough and cold ingredient. Of these 118 cases, 103
      involved a nonprescription drug, whereas 15 cases involved a prescription
      medication alone. Of 103 cases associated with nonprescription drugs, the
      evidence indicated that 88 involved an overdosage. A dosage could not be assessed
      in the remaining 15 cases. Several contributing factors were identified: age
      younger than 2 years, use of the medication for sedation, use in a daycare
      setting, use of 2 medicines with the same ingredient, failure to use a measuring
      device, product misidentification, and use of a nonprescription product intended
      for adult use. All cases that occurred in a daycare setting involved a child
      younger than 2 years. CONCLUSION: In our sample, pediatric fatalities caused by
      nonprescription cough and cold medications were uncommon, involved overdose, and
      primarily affected children younger than 2 years. The intent of caregivers
      appears to be therapeutic to relieve symptoms in some cases and nontherapeutic to
      induce sedation or to facilitate child maltreatment in other cases.

PMID- 19101061
TI  - Effects of collector types in sampling of atmospheric depositional fluxes.
AB  - The bulk gross alpha, gross beta and (7)Be depositional fluxes were measured in
      Malaga (36.7 degrees N, 4.5 degrees W), a coastal Mediterranean station in the
      south of Spain for one whole year. In order to quantify the local variation of
      deposition rates, we have analysed the monthly results from two deposition
      collectors: a "pot "collector with a continuous water-covered surface and a
      "funnel" collector. In general, the alpha and beta depositional fluxes from the
      funnel collector were approximately two times lower than the pot collector.
      Whereas for the cosmogenic (7)Be, the depositional flux of (7)Be from funnel
      collector was also approximately two times lower than the pot collector. A good
      correlation of the depositional flux of (7)Be has been obtained from both
      collectors.

PMID- 19101062
TI  - Removal of uranium (VI) from aqueous solution by adsorption of hematite.
AB  - Hematite, a type of inorganic-sorptive medium, was used for the removal of U (VI)
      from aqueous solutions. Variables of the batch experiments including solution pH,
      contact time, initial concentration, temperature, calcium and magnesium ions were
      studied. The results indicated that the adsorption capacities are strongly
      affected by the solution pH, contact time and initial concentration. A higher pH
      favors higher U (VI) removal. The adsorption was also affected by temperature and
      calcium and magnesium ions, but the effect is very weak. The maximum adsorption
      capacity (q(m)) only increased from 3.36 mgg(-1) to 3.54 mgg(-1) when the
      temperature was increased from 293 K to 318 K. A two-stage kinetic behavior was
      observed in the adsorption of uranium (VI): very rapid initial adsorption in a
      few minutes, followed by a long period of slower uptake. It was found that an
      increase in temperature resulted in a higher uranium (VI) loading per unit weight
      of the sorbent. The adsorption of uranium by hematite had good efficiency, and
      the equilibrium time of adsorbing uranium (VI) was about 6h. The isothermal data
      were fitted with both Langmuir and Freundlich equations, but the data fitted the
      former better than the latter. The pseudo-first-order kinetic model, pseudo
      second-order kinetic model and intraparticle diffusion model were used to
      describe the kinetic data, but the pseudo-second-order kinetic model was the
      best. The thermodynamic parameter Delta G(0) were calculated, the negative Delta
      G(0) values of uranium (VI) at different temperatures confirmed the adsorption
      processes were spontaneous.

PMID- 19101063
TI  - The virus stops with me: HIV-infected Ugandans' motivations in preventing HIV
      transmission.
AB  - Few Positive Prevention interventions have been implemented in Africa; however,
      greater attention is now being paid to interventions that include messages of
      personal responsibility or altruism that may motivate HIV-infected individuals
      towards HIV prevention behaviors in Africa. We conducted 47 in-depth interviews
      in 2004 with HIV-infected men and women purposefully sampled to represent a range
      of sexual activities among clients of an AIDS support organization in Uganda.
      Qualitative interviews were selected from a cross-sectional survey of 1092 HIV
      infected men and women. Clients were interviewed about their concerns around
      sexual HIV transmission, feelings of responsibility and reasons for these
      feelings, as well as about the challenges and consequences of actions to prevent
      HIV transmission. The reasons they provided for their sense of prevention
      responsibility revolved around ethical and practical themes. Responsibility
      toward sexual partners was linked to the belief that conscious transmission of
      HIV equals murder, would cause physical and emotional harm, and would leave
      children orphaned. The primary reason specific to preventing HIV transmission to
      unborn children was the perception that they are 'innocent'. Most participants
      felt that HIV-infected individuals held a greater responsibility for preventing
      HIV transmission than did HIV-uninfected individuals. Respondents reported that
      their sense of responsibility lead them to reduce HIV transmission risk,
      encourage partner testing, disclose HIV test results, and assume an HIV/AIDS
      educator role. Challenges to HIV preventive behavior and altruistic intentions
      included: sexual desire; inconsistent condom use, especially in long term
      relationships; myths around condom use; fear of disclosure; gender-power
      dynamics; and social and financial pressure. Our finding that altruism played an
      important role in motivating preventive behaviors among HIV-infected persons in
      Uganda supports the inclusion of altruistic prevention and counseling messages
      within Positive Prevention interventions.

PMID- 19101065
TI  - Event-related potential correlates of visual identity negative priming unbiased
      by trial-by-trial effects.
AB  - Negative priming (NP) refers to slowed reaction times and/or less accurate
      responses in people responding to a target that was ignored on a previous trial.
      Although extensive research with behavioral measures has been conducted, little
      is known about the electrophysiological mechanisms underlying this effect. The
      few previous studies carried out have led to contradictory results, supporting
      either episodic-retrieval or inhibition-based theoretical perspectives. In this
      study, we analyzed the ERP correlates of negative priming by using an
      experimental global context which, similar to the NP standard context, included
      Attended repetition trials. In addition, we presented relevant stimuli in
      separate blocks instead of the more usual randomized design. The NP effect can be
      biased by strategies adopted by participants when attended and ignored repetition
      trials are presented randomly. Specifically, we observed an enhanced N2 when a
      distractor from the previous trial became the target in the next trial. It is
      supposed that this finding reflects the involvement of additional attentional
      resources in the selection of a previously inhibited distractor as the new target
      stimuli.

PMID- 19101067
TI  - Electronic structures, DNA-binding and spectral properties of Co(III) complexes
      [Co(bpy)2(L)]3+ (L=pip, odhip, hnoip).
AB  - Studies on the electronic structures and trend in DNA-binding affinities of a
      series of Co(III) complexes have been carried out, using the density functional
      theory (DFT) at the B3LYP/LanL2DZ level. The optimized geometric structures of
      these Co(III) complexes in aqueous solution are more close to experimental data
      than those in vacuo. The electronic structures of these Co(III) complexes were
      analyzed on the basis of their geometric structures optimized in aqueous
      solution, and the trend in the DNA-binding constants (K(b)) was reasonably
      explained. In addition, the electronic absorption spectra of these complexes were
      calculated and simulated in aqueous solution using the time dependent DFT (TDDFT)
      at the B3LYP/LanL2DZ level. The calculated absorption spectra of these Co(III)
      complexes in aqueous solution are in satisfying agreement with experimental
      results, and the properties of experimental absorption bands have been
      theoretically explained in detail. Meanwhile, in order to explore the solvent
      effect on the absorption spectra of these Co(III) complexes, their absorption
      spectra in vacuo were also calculated, and the results show that the calculated
      absorption spectra of Co(III) complexes are greatly influenced by the solvent
      effect.

PMID- 19101066
TI  - An integrative simulation model linking major biochemical reactions of actin
      polymerization to structural properties of actin filaments.
AB  - We report on an advanced universal Monte Carlo simulation model of actin
      polymerization processes offering a broad application panel. The model integrates
      major actin-related reactions, such as assembly of actin nuclei,
      association/dissociation of monomers to filament ends, ATP-hydrolysis via ADP-Pi
      formation and ADP-ATP exchange, filament branching, fragmentation and annealing
      or the effects of regulatory proteins. Importantly, these reactions are linked to
      information on the nucleotide state of actin subunits in filaments (ATP
      hydrolysis) and the distribution of actin filament lengths. The developed
      stochastic simulation modelling schemes were validated on: i) synthetic
      theoretical data generated by a deterministic model and ii) sets of our and
      published experimental data obtained from fluorescence pyrene-actin experiments.
      Build on an open-architecture principle, the designed model can be extended for
      predictive evaluation of the activities of other actin-interacting proteins and
      can be applied for the analysis of experimental pyrene actin-based or
      fluorescence microscopy data. We provide a user-friendly, free software package
      ActinSimChem that integrates the implemented simulation algorithms and that is
      made available to the scientific community for modelling in silico any specific
      actin-polymerization system.

PMID- 19101064
TI  - An evaluation of recollection and familiarity in Alzheimer's disease and mild
      cognitive impairment using receiver operating characteristics.
AB  - There is a need to investigate exactly how memory breaks down in the course of
      Alzheimer's disease (AD). Examining what aspects of memorial processing remain
      relatively intact early in the disease process will allow us to develop
      behavioral interventions and possible drug therapies focused on these intact
      processes. Several recent studies have worked to understand the processes of
      recollection and familiarity in patients with mild cognitive impairment (MCI) and
      very mild AD. Although there is general agreement that these patient groups are
      relatively unable to use recollection to support veridical recognition decisions,
      there has been some question as to how well these patients can use familiarity.
      The current study used receiver operating characteristic (ROC) curves and a depth
      of processing manipulation to understand the effect of MCI and AD on the
      estimates of recollection and familiarity. Results showed that patients with MCI
      and AD were impaired in both recollection and familiarity, regardless of the
      depth of encoding. These results are discussed in relation to disease pathology
      and in the context of recent conflicting evidence as to whether familiarity
      remains intact in patients with MCI. The authors highlight differences in stimuli
      type and task difficulty as possibly modulating the ability of these patients to
      successfully use familiarity in support of memorial decisions.

PMID- 19101068
TI  - Alpha-synuclein aggregation variable temperature and variable pH kinetic data: a
      re-analysis using the Finke-Watzky 2-step model of nucleation and autocatalytic
      growth.
AB  - The aggregation of proteins is believed to be intimately connected to many
      neurodegenerative disorders. We recently reported an "Ockham's
      razor"/minimalistic approach to analyze the kinetic data of protein aggregation
      using the Finke-Watzky (F-W) 2-step model of nucleation (A-->B, rate constant
      k(1)) and autocatalytic growth (A+B-->2B, rate constant k(2)). With that kinetic
      model we have analyzed 41 representative protein aggregation data sets in two
      recent publications, including amyloid beta, alpha-synuclein, polyglutamine, and
      prion proteins (Morris, A. M., et al. (2008) Biochemistry 47, 2413-2427; Watzky,
      M. A., et al. (2008) Biochemistry 47, 10790-10800). Herein we use the F-W model
      to reanalyze protein aggregation kinetic data obtained under the experimental
      conditions of variable temperature or pH 2.0 to 8.5. We provide the average
      nucleation (k(1)) and growth (k(2)) rate constants and correlations with variable
      temperature or varying pH for the protein alpha-synuclein. From the variable
      temperature data, activation parameters DeltaG(double dagger), DeltaH(double
      dagger), and DeltaS(double dagger) are provided for nucleation and growth, and
      those values are compared to the available parameters reported in the previous
      literature determined using an empirical method. Our activation parameters
      suggest that nucleation and growth are energetically similar for alpha-synuclein
      aggregation (DeltaG(double dagger)(nucleation)=23(3) kcal/mol; DeltaG(double
      dagger)(growth)=22(1) kcal/mol at 37 degrees C). From the variable pH data, the F
      W analyses show a maximal k(1) value at pH approximately 3, as well as minimal
      k(1) near the isoelectric point (pI) of alpha-synuclein. Since solubility and net
      charge are minimized at the pI, either or both of these factors may be important
      in determining the kinetics of the nucleation step. On the other hand, the k(2)
      values increase with decreasing pH (i.e., do not appear to have a minimum or
      maximum near the pI) which, when combined with the k(1) vs. pH (and pI) data,
      suggest that solubility and charge are less important factors for growth, and
      that charge is important in the k(1), nucleation step of alpha-synuclein. The
      chemically well-defined nucleation (k(1)) rate constants obtained from the F-W
      analysis are, as expected, different than the 1/lag-time empirical constants
      previously obtained. However, k(2)x[A](0) (where k(2) is the rate constant for
      autocatalytic growth and [A](0) is the initial protein concentration) is related
      to the empirical constant, k(app) obtained previously. Overall, the average
      nucleation and average growth rate constants for alpha-synuclein aggregation as a
      function of pH and variable temperature have been quantitated. Those values
      support the previously suggested formation of a partially folded intermediate
      that promotes aggregation under high temperature or acidic conditions.

PMID- 19101069
TI  - beta-catenin is involved in N-cadherin-dependent adhesion, but not in canonical
      Wnt signaling in E2A-PBX1-positive B acute lymphoblastic leukemia cells.
AB  - OBJECTIVE: The t(1;19)(q23;13) translocation, resulting in the production of the
      E2A-PBX1 chimeric protein, is a common nonrandom translocation in pediatric B
      lineage acute lymphoblastic leukemia (B-ALL). The E2A-PBX1 chimeric protein
      activates expression of several genes, including Wnt16. In the present study, we
      explored the role of Wnt16 and beta-catenin in t(1;19) B-ALL cells. MATERIALS AND
      METHODS: Canonical Wnt signaling was measured by TOPflash activity. Localization
      of beta-catenin in the cell membrane and its involvement in leukemia-stroma
      interaction were studied by confocal microscopy. Adhesion to N-cadherin was
      analyzed by adding (3)H-thymidin-labeled cells to N-cadherin-coated wells.
      RESULTS: In contrast to previous reports, we detected no effects on cell
      viability or proliferation upon modulation of the Wnt16 levels. Moreover, despite
      high levels of Wnt16 and beta-catenin, the cells had very low levels of canonical
      Wnt signaling. Instead, beta-catenin was located in the cell membrane along with
      N-cadherin. E2A-PBX1-positive leukemia cells adhered strongly to bone marrow
      stroma cells, and we showed that adherence junctions stained strongly for both
      proteins. Moreover, knockdown of beta-catenin reduced the adhesion of E2A-PBX1
      positive leukemia cells to N-cadherin, suggesting that beta-catenin and N
      cadherin play a central role in homotypic cell-to-cell adhesion and in leukemia
      stroma adhesion. Interestingly, knockdown of Wnt16 by small interfering RNA
      reduced the level of N-cadherin. CONCLUSION: Wnt16 does not activate canonical
      Wnt signaling in E2A-PBX1-positive cells. Instead, beta-catenin is involved in N
      cadherin-dependent adherence junctions, suggesting for the first time that
      leukemia-stroma interactions may be mediated via an N-cadherin-dependent
      mechanism.

PMID- 19101070
TI  - ABCG2 expression is correlated neither to side population nor to hematopoietic
      progenitor function in human umbilical cord blood.
AB  - OBJECTIVE: The ABCG2 transporter has been identified as a determinant of the side
      population (SP) in murine bone marrow and a potential marker for primitive stem
      cells. To assess the potential of the SP phenotype and ABCG2 expression to
      identify stem cells in human umbilical cord blood (hUCB), we have examined
      directly the relationship between SP; expression of ABCG2, CD133, and CD34; and
      hematopoietic potential in UCB samples. MATERIALS AND METHODS: Multicolor
      fluorescence activated cell sorting analysis was combined with the Hoechst SP
      procedure to allow the simultaneous detection of the SP phenotype together with
      surface markers in cells from fresh and cryopreserved UCB. Sorted populations
      were analyzed for cobblestone area-forming cell (CAFC) activity and by
      quantitative reverse transcriptase polymerase chain reaction for expression of
      mRNA from the ABC transporters ABCG2, MDR1, and MRP1. ABCG2(+) cells were
      enriched by magnetic-activated cell sorting for stringent analysis. RESULTS: hUCB
      derived SP cells were negative for ABCG2, but comprise approximately 20%
      CD133(+)/CD34(+) cells. Sorted SP cells from UCB were enriched 20-fold for week
      13 CAFC activity, while magnetic-activated cell sorting-enriched ABCG2(+) cells
      retained no hematopoietic activity either in CAFC or liquid cultures. There was
      no significant difference in the SP frequency, immunophenotype, or CAFC potential
      of fresh and cryopreserved UCB. ABCG2 mRNA was not enriched in the SP and was
      specifically diminished ninefold in CD133 cells, which were eightfold enriched
      for MDR1 mRNA. CONCLUSION: We find no evidence for an association of ABCG2 with
      SP activity or hematopoietic progenitor function in hUCB.

PMID- 19101071
TI  - Industrial and urban symbiosis in Japan: analysis of the Eco-Town Program 1997
      2006.
AB  - Japan's Eco-Town Program spearheaded in Japan the integration of Industrial
      Symbiosis and Urban Symbiosis, seeking to maximise the economic and environmental
      benefit from close geographic proximity of industrial and urban areas, through
      the use of previously discarded commercial, municipal and industrial waste
      materials in industrial applications. The program established 26 Eco-Towns around
      Japan. Approximately 1.65 billion USD was invested in 61 innovative recycling
      projects, with an average government subsidy of 36%. In addition at least 107
      other recycling facilities have been constructed without government subsidy. 14
      Eco-Towns primarily contributed to improving industry's productivity, whilst 10
      Eco-Towns primarily contributed to improving environmental amenity. In 16 Eco
      Towns the private sector was the most important actor supporting local government
      in the realisation of the Eco-Town, whilst in 9 Eco-Towns this was civil society.
      The availability of investment subsidies, the coming into force of ambitious
      recycling legislation with quantified, product-specific targets, access to the
      significant technological resources of the private sector, and widespread
      recognition of the urgency to act on environmental issues, all contributed to the
      success of the Eco-Town Program.

PMID- 19101072
TI  - Development of a water quality loading index based on water quality modeling.
AB  - Water quality modeling is an ideal tool for simulating physical, chemical, and
      biological changes in aquatic systems. It has been utilized in a number of GIS
      based water quality management and analysis applications. However, there is
      considerable need for a decision-making process to translate the modeling result
      into an understandable form and thereby help users to make relevant judgments and
      decisions. This paper introduces a water quality index termed QUAL2E water
      quality loading index (QWQLI). This new WQI is based on water quality modeling by
      QUAL2E, which is a popular steady-state model for the water quality of rivers and
      streams. An experiment applying the index to the Sapgyo River in Korea was
      implemented. Unlike other WQIs, the proposed index is specifically used for
      simulated water quality using QUAL2E to mainly reflect pollutant loading levels.
      Based on the index, an iterative modeling-judgment process was designed to make
      decisions to decrease input pollutants from pollutant sources. Furthermore, an
      indexing and decision analysis can be performed in a GIS framework, which can
      provide various spatial analyses. This can facilitate the decision-making process
      under various scenarios considering spatial variability. The result shows that
      the index can evaluate and classify the simulation results using QUAL2E and that
      it can effectively identify the elements that should be improved in the decision
      making process. In addition, the results imply that further study should be
      carried out to automate algorithms and subsidiary programs supporting the
      decision-making process.

PMID- 19101073
TI  - Evaluation of tissue mimicking quality of tofu for biomedical ultrasound.
AB  - The tissue mimicking quality of tofu has been evaluated in terms of acoustic
      properties and acousto/thermal conversion as functions of frequency and
      diffraction corrected intensity over the 2 MHz to 18 MHz range using three
      unfocussed transducers with center frequencies of 5 MHz, 10 MHz and 15 MHz. The
      density and acoustic velocity were close to the American Institute of Ultrasound
      in Medicine (AIUM) recommended values for the soft tissue, however, the
      attenuation increases nonlinearly with frequency as alpha = 0.56 x f(1.3). As a
      result, the temperature rise in tofu due to ultrasound absorption is expressed by
      the product of the acousto/thermal conversion factor and the
      attenuation/diffraction corrected acoustic intensity. The decrease of temperature
      rise with depth measured by embedded thermocouples agrees with the theoretical
      exponential decrease of the attenuation/diffraction corrected acoustic intensity.
      The heat capacity per unit mass of tofu is 0.76 cal/g degrees C (equivalent to
      3.18 J/g degrees C) of which about 76% is water. The nonlinear frequency
      dependence of attenuation in tofu as f(1.3) correctly describes the frequency
      dependence of temperature rise. The present results suggest that tofu may only be
      used in a limited low MHz range in view of the estimation of temperature rise and
      penetration depth due to nonlinear frequency dependence of attenuation.

PMID- 19101074
TI  - Editorial comment on: Robotic-assisted laparoscopic extended pelvic lymph node
      dissection for prostate cancer: surgical technique and experience with the first
      99 cases.

PMID- 19101075
TI  - Editorial comment on: Robotic-assisted laparoscopic extended pelvic lymph node
      dissection for prostate cancer: surgical technique and experience with the first
      99 cases.

PMID- 19101076
TI  - Robotic-assisted laparoscopic extended pelvic lymph node dissection for prostate
      cancer: surgical technique and experience with the first 99 cases.
AB  - BACKGROUND: To date, there is still a paucity of data in the literature on
      robotic-assisted laparoscopic extended pelvic lymph node dissection (RALEPLND) in
      patients with prostate cancer. OBJECTIVE: To assess the technical feasibility of
      RALEPLND and to present our surgical technique. DESIGN, SETTING, AND
      PARTICIPANTS: From April 2006 to March 2008, we performed RALEPLND in 99 patients
      prior to robotic-assisted laparoscopic radical prostatectomy. Indications for
      RALEPLND were a prostate-specific antigen (PSA) > or = 10 ng/ml or a preoperative
      Gleason score > or = 7. The data were evaluated retrospectively. SURGICAL
      PROCEDURE: The transperitoneal approach was used in all cases. In order to gain
      optimal access to the common iliac bifurcation, the five trocars were placed in a
      more cephalad position than in patients undergoing radical prostatectomy without
      RALEPLND. After identification of important landmarks, the lymphatics covering
      the external iliac vein, the obturator lymphatic packet, and the lymphatics
      overlying the internal iliac artery were removed on both sides. MEASUREMENTS: The
      total lymph node yield, the frequency of lymph node metastases, and the
      complication rate. RESULTS AND LIMITATIONS: The median patient age was 64 yr
      (range: 45-78). The median preoperative PSA level was 7.7 ng/ml (range: 1.5
      84.6). The median number of lymph nodes harvested was 19 (range: 8-53). In 16
      patients (16%), we found lymph node metastasis. Complications occurred in seven
      patients (7%). CONCLUSIONS: RALEPLND is feasible, and its lymph node yield is
      well in the range of open series. The robotic-assisted laparoscopic approach in
      itself does not seem to limit a surgeon's ability to perform a complete extended
      pelvic lymph node dissection.

PMID- 19101077
TI  - Mirror movements and involuntary homolateral limb synkinesis in a patient with
      probable Creutzfeldt-Jakob disease.
AB  - We report a 63-year-old man, who was diagnosed with probable Creutzfeldt-Jakob
      disease, manifested by rapid progressive cognitive decline, gait disturbance,
      right focal hand dystonia, myoclonus, mirror movements, and involuntary
      homolateral limb synkinesis during alternating limb movements. Although the exact
      pathophysiology for contralateral and homolateral limb synkinesis is not known,
      dysfunction of the secondary motor areas and dorsal premotor cortex by spongiform
      degeneration of gray matter may cause these abnormalities.

PMID- 19101078
TI  - Impact of the lunar cycle on the incidence of aneurysmal subarachnoid
      haemorrhage: myth or reality?
AB  - OBJECTIVE: To investigate the impact of the lunar cycle on the incidence of
      aneurysmal subarachnoid haemorrhages. METHODS: We retrospectively identified all
      patients admitted to the department of neurosurgery during 1992 and 2004
      suffering from aneurysmal subarachnoid haemorrhage. The onset of bleeding was
      compared with the lunar phase. RESULTS: We did not observe any significant impact
      of the lunar cycle on the incidence of aneurysmal subarachnoid haemorrhage in 717
      consecutive patients (p=0.84). CONCLUSION: The impact of the lunar cycle on
      aneurysmal subarachnoid haemorrhage is a myth rather than reality.

PMID- 19101079
TI  - Factors associated with brainstem congestive encephalopathy in dural arterio
      venous fistulas.
AB  - OBJECTIVES: Cranial dural arterio-venous fistulas (DAVFs) are unique neuro
      vascular entities that represent 10-15% of all intra-cranial arterio-venous
      lesions. This study describes the clinical characteristics and neuro-imaging
      findings of patients with posterior fossa DAVFs. METHODS: Twenty adult patients
      with posterior fossa DAVFs were enrolled in this 5-year retrospective study. The
      clinical details of seven patients with venous congestive encephalopathy are
      described, and patients with and those without brainstem encephalopathy were
      compared. RESULTS: Seven of 20 patients (35%) had brainstem venous congestive
      encephalopathy complicating the posterior fossa DAVFs. Patients with aggressive
      clinical symptomatology, aggressive Borden or Cognard classifications, and
      anterior venous draining patterns had higher risks of brainstem venous congestive
      encephalopathy. In terms of Glasgow outcome scale, one patient had moderate
      disabilities, five had severe disabilities, and one expired. CONCLUSIONS:
      Although most patients had good Glasgow coma scores with varying degrees of
      clinical symptoms on admission, those with brainstem venous congestive
      encephalopathy had poor outcomes despite full resolution of the cortical vein
      reflux.

PMID- 19101080
TI  - Spinal meningioma: chronicles of contemporary neurosurgical diagnosis and
      management.
AB  - Spinal meningiomas are uncommon entities that fortunately burden only a small
      minority of patients. Notwithstanding their overwhelmingly benign propensity, the
      occurrence of extramedullary meningioma may nonetheless cause significant
      morbidity and possible mortality. The consideration therefore, of spinal
      meningioma in the differential of patients presenting with radiculopathy or
      complaints of chronic back or neck pain should not be disregarded. The rapidity
      of diagnosis and the first neurosurgical encounter are cornerstones in patient
      longevity and neurological preservation. The advent of microsurgical techniques
      and magnetic resonance imaging and surgical techniques has notably improved
      clinical outcomes over the past two decades. However, surgical candidacy may be
      limited, particularly in those patients with significant preexisting medical
      comorbidities, aggressive or recurring tumors, or multiple lesions. Alternative
      management strategies such as stereotactic radiosurgery or less invasive surgical
      techniques are currently underway in clinical practice. A review on neurosurgical
      diagnosis and treatment modalities in the management of spinal meningioma is
      therefore pertinent.

PMID- 19101081
TI  - The inhibitory effect of diarylpropionitrile, a selective agonist of estrogen
      receptor beta, on the growth of MC38 colon cancer line.
AB  - The protective role of estrogens in the colon carcinogenesis has been suggested
      for many years and attributed mainly to estrogen receptor beta (ERbeta). However,
      the direct effect of estrogens and their action through ERbeta on the growth of
      colon cancer have been rarely studied. The aim of this study was to examine the
      effect of various concentrations (10(-4)-10(-12)M) of diarylpropionitrile (DPN)-
      a selective agonist of ERbeta--on the growth of murine MC38 colon cancer line.
      Moreover, the aim of this paper was the immunohistochemical assessment of
      estrogen and progesterone receptor expression in human colon tissues and in MC38
      cells (only ERbeta). We found that DPN induced a growth inhibition of MC38 cancer
      (50-94% of control group) at the highest (10(-4)M) and two lowest concentrations
      (10(-11) and 10(-12)M). Furthermore, we detected a nuclear-cytoplasmic expression
      of ERbeta in human normal and neoplastic colon tissues and in the studied MC38
      cancer cells. The inhibitory effect of DPN on the growth of MC38 colon cancer
      line suggests a possibility of using a selective estrogen receptor agonist in the
      treatment of colon cancer.

PMID- 19101082
TI  - HDAC inhibitors in models of inflammation-related tumorigenesis.
AB  - Histone deacetylase (HDAC) inhibitors have been described in detail for their
      anti-proliferative potency. Recently, an anti-inflammatory property was
      characterized in vitro and in vivo. This dual efficacy of HDAC inhibitors is
      highly attractive, since chronic inflammations such as ulcerative colitis are
      associated with an increased risk of developing carcinomas. Additionally, in
      models of colitis and inflammation-induced tumorigenesis inflammation as well as
      tumor development was significantly inhibited by HDAC inhibitor treatment. The
      mechanisms involved reach beyond the simple regulation of histone acetylation and
      deacetylation. The currently known key target structures and mechanisms mediating
      this dual effect will be discussed in this review.

PMID- 19101083
TI  - Prediction of impact sensitivity of nitro energetic compounds by neural network
      based on electrotopological-state indices.
AB  - A quantitative structure-property relationship (QSPR) model was constructed to
      predict the impact sensitivity of 156 nitro energetic compounds by means of
      artificial neural network (ANN). Electrotopological-state indices (ETSI) were
      used as molecular structure descriptors which combined together both electronic
      and topological characteristics of the analyzed molecules. The typical back
      propagation neural network (BPNN) was employed for fitting the possible non
      linear relationship existed between the ETSI and impact sensitivity. The dataset
      of 156 nitro compounds was randomly divided into a training set (64), a
      validation set (63) and a prediction set (29). The optimal condition of the
      neural network was obtained by adjusting various parameters by trial-and-error.
      Simulated with the final optimum BP neural network [16-12-1], the results show
      that most of the predicted impact sensitivity values are in good agreement with
      the experimental data, which are superior to those obtained by multiple linear
      regression (MLR) and partial least squares (PLS). The model proposed can be used
      not only to reveal the quantitative relation between impact sensitivity and
      molecular structures of nitro energetic compounds, but also to predict the impact
      sensitivity of nitro compounds for engineering.

PMID- 19101084
TI  - Zirconium oxidation on the atomic scale.
AB  - Zirconium alloys are used in the nuclear industry as fuel rod cladding. They are
      chosen for this role because of their good mechanical properties and low thermal
      neutron absorption. Oxidation of these alloys by coolant is one of the chief
      limiting factors of the fuel burn-up efficiency. The aim of the present study is
      to understand these oxidation mechanisms. As a first step, a fundamental study of
      the oxidation of commercially pure zirconium has been conducted using the 3D atom
      probe (3DAP). The current generation of 3DAPs allows both voltage and laser
      pulsing, providing data sets of many millions of ions. According to the
      literature the only stable oxide of zirconium is ZrO(2). However, the 3DAP shows
      that an initial layer a few nanometres thick forms with a composition of ZrO(1
      )(x) when subjected to light oxidation. This result confirms and extends the work
      of Wadman et al. [Colloque de Physique 50 (1989) C8 303; Journal de Physique, 11
      (1988) C6 49] and Wadman and Andren [in: C.M. Euchen, A.M. Garde (Eds.),
      Zirconium in the Nuclear Industry: Ninth Symposium, ASTM STP 1132, ASTM, USA,
      1991, p. 461], who used 1DAP techniques, obtaining reduced data sets. Segregation
      of hydrogen to the metal-oxide interface and a distinct ZrH phase were observed
      in this study. A novel kinetics study of the room temperature oxidation of
      zirconium showed the ZrO layer to be non-protective over the time period
      investigated (up to 1h).

PMID- 19101085
TI  - Achieving uniform field emission from carbon nanotube composite cold cathode with
      different carbon nanotube contents: effects of conductance and plasma treatment.
AB  - A carbon nanotube (CNT) composite cold cathode was studied for field emission
      display application. The CNT composite cold cathode was composed of CNTs and
      silicon dioxide binder. Field emission from CNT composite cold cathode with
      different CNT contents was studied. It was found that with increase in CNT
      contents, the threshold field decreased. The conductance of the composite cathode
      was measured and with increasing CNT content, there was a critical CNT content
      where the conductance increased several orders of magnitude. Plasma etching using
      SF(6) as the etchant was adopted to treat the cathode. Improvement in emission
      uniformity was achieved. It was also found that after post-treatment the
      threshold field of the cathode decreased. The morphology of the etched cathode
      was analyzed and the improvement of uniformity and lowering of the threshold
      field was attributed to the exposure of CNTs after etching.

PMID- 19101086
TI  - Molecular characterisation of Cryptosporidium isolates from pet reptiles.
AB  - In this study, we investigated the presence of Cryptosporidium in 171 faecal
      samples from reptiles commonly used as pet animals. These include lizards
      belonging to the genera Eublepharis, Pogona, Chlamydosaurus, Hemiteconyx,
      Teratoscincus, Tiliqua, Iguana, and Chamaeleo, snakes of the genera Lampropeltis,
      Elaphe, Python, Boa and Corallus, and tortoises belonging to the genera Testudo
      and Kinixys. Cryptosporidium oocysts were detected by immunofluorescence using a
      commercially available kit and cryptosporidial DNA by amplification of a
      polymorphic fragment of the 18S rDNA and the HSP70 locus. Cryptosporidium was
      detected in 38.6% and 25.1% of the samples analysed by immunofluorescence and
      PCR, respectively. Molecular characterisation of the isolates confirmed that C.
      serpentis and C. varanii (syn. C. saurophilum) are the main species involved in
      infection in pet reptiles but also showed the presence of C. parvum and C. muris,
      as well as other species or genotypes of this parasite including the
      Cryptosporidium mouse genotype and Cryptosporidium tortoise genotype previously
      described in reptiles. In addition, a Cryptosporidium sp. was isolated from a
      chameleon and a python.

PMID- 19101087
TI  - Survey of bovine trypanosomosis in the Kachia Grazing Reserve, Kaduna State,
      Nigeria.
AB  - This study assessed the prevalence of trypanosomes in cattle at the Kachia
      Grazing Reserve (KGR) in March and June 2004 and in February 2005. A total of
      1293 cattle blood samples were collected at random. The samples were analysed
      using the buffy coat technique and Giemsa thin blood films for parasite detection
      and identification. The effects of herd pen location to watering and grazing
      point's distances (using the global positioning system (GPS)) were determined and
      mean Packed cell volume (PCV) assessed. Overall, the detected prevalence of
      trypanosomosis was 8.4%, much higher than the previous prevalence of 5.3% before
      the present study was conducted. The prevalences in the months of March, June
      (2004) and February (2005) were 2.3%, 11.6% and 15.4%, respectively. Increased
      prevalence was associated with proximity of herd pens to watering point's
      distances (chi(2) for linear trend=4.447, P<0.05), but no association of herd
      pens to grazing point distances (chi(2)=2.186, P>0.05); suggesting that
      hydrological network played an important part in trypanosomosis transmission. The
      mean PCV of parasitaemic and apparasitaemic cattle were respectively 25.99+/
      1.82% and 29.31+/-1.70%. The drop in mean PCV was most in 0-1-year age group,
      23.47+/-3.10% and was statistically significant (P<0.05), suggesting that anaemia
      was most pronounced in this age group. Factors that may have contributed to the
      increased prevalence obtained were collapse of control measures and breed
      susceptibility. Since, Zebu cattle were the predominant breeds in the reserve,
      the study advocates effective use of insecticide impregnated screens (traps and
      targets) with community participation in mind for sustainability. If government
      intervenes through PATTEC ground spraying of insecticides in the reserve is
      recommended. In addition, chemotherapeutic and chemoprophylaxis should be
      systematically used to fight the problem of trypanosomosis in the KGR towards
      improved livestock production.

PMID- 19101088
TI  - Definition of meditation: Seeking a consensus.

PMID- 19101089
TI  - A hypothesis on factors influencing preferences in positioning of scalp hair
      parting line.

PMID- 19101090
TI  - Could cells from menstrual blood be a new source for cell-based therapies?
AB  - Human endometrium is a highly regenerative tissue and contains a low number of
      cells which have high replicative ability and differentiation efficiency. This
      has been identified by many scientists. When the fresh growth of tissue and blood
      vessels is shed during each menstrual cycle, some cells with regenerative
      capabilities are present. Reports have also indicated that these cells possess
      the capacity to trans-differentiate into mesodermal, ectodermal and endodermal
      lineages by using standard commercially available culture reagents and
      methodologies. Given the ease of extraction and pluripotency of this cell
      population, we propose it as a novel alternative to current cells sources for
      cell-based therapies.

PMID- 19101091
TI  - Trends and patterns of breast conservation treatment in Hong Kong: 1994-2007.
AB  - PURPOSE: Breast conservation treatment (BCT) was quite unpopular in Hong Kong
      until the early 1990s, but the trends and patterns of BCT use in the past 14
      years have not been studied since. The purpose of this study was to identify the
      latest trends and patterns. METHODS AND MATERIALS: All consecutive cases of
      female breast cancer referred to a community oncology center in Hong Kong between
      1994 and 2007 were retrospectively reviewed. Of the 2,375 women with T1-2
      invasive breast cancer who underwent surgery, 1,137 (48%) had T1 (</=2 cm)
      disease and 1,238 (52%) had T2 (>2 cm-</=5 cm) disease. Median patient age was 51
      years (range, 24-95 years); 65% patients had their surgery in public hospitals.
      RESULTS: Of the total patient cohort, 2,153 (91%) patients presented with
      palpable breast masses and only 104 (4%) with mammographically detected cancers.
      Overall, 721 (30%) and 1,654 (70%) patients underwent BCT and mastectomy,
      respectively. There was no significant increase in the BCT rates (31%, SD 5%; p =
      0.804) or mammographic detection rates (5%, SD 1%; p = 0.125) in Hong Kong
      between 1994 and 2007. In multivariate analyses, age </=50 years (OR 2.479; p <
      0.001), mammographically detected tumors (OR 1.868; p = 0.007), T1 tumors (OR
      3.159; p < 0.001), surgeries in private hospitals (OR 1.288; p = 0.018), and
      negative nodal status (OR 1.886; p < 0.001) were independent factors predictive
      of a higher likelihood of a woman having BCT. CONCLUSIONS: Our results indicate a
      satisfactory acceptance of BCT by patients who are young and have small tumors,
      node-negative disease, or surgery in private hospitals. However, the continuing
      unpopularity of breast screening is likely a major factor limiting the broad use
      of BCT.

PMID- 19101092
TI  - Correlation among six biologic factors (p53, p21(WAF1), MIB-1, EGFR, HER2, and
      Bcl-2) and clinical outcomes after curative chemoradiation therapy in squamous
      cell cervical cancer.
AB  - PURPOSE: The expressions of six cell-cycle-associated proteins were analyzed in
      cervical squamous cell carcinomas in correlation in a search for prognostic
      correlations in tumors treated with concurrent chemoradiation therapy (cCRT).
      METHODS AND MATERIALS: The expressions of p53, p21/waf1/cip1, molecular
      immunology borstel-1 (MIB-1), epidermal growth factor receptor (EGFR), human
      epidermal growth factor receptor type 2 (HER2), and Bcl-2 were studied using an
      immunohistochemical method in 57 cases of cervical squamous cell carcinoma
      treated with cCRT. Patients received cCRT between 1998 and 2005. The mean patient
      age was 61 years (range, 27-82 years). The number of patients with Stage II, III,
      and IVA disease was 18, 29, and 10, respectively. RESULTS: The number of patients
      with tumors positive for p53, p21/waf1/cip1, MIB-1, EGFR, HER2, and Bcl-2 was 26,
      24, 49, 26, 13, and 11, respectively; no significant correlation was noted. The 5
      year overall survival rates of HER2-positive and -negative patients was 76% vs.
      44%, which was of borderline significance (p = 0.0675). No significant
      correlation was noted between overall survival and expressions of p53,
      p21/waf1/cip1, MIB-1, EGFR, and Bcl-2. No correlation was observed between local
      control and expression of any of the proteins. CONCLUSION: Expression of HER2
      protein had a weak impact of borderline significance on overall survival in
      squamous cell carcinoma of the uterine cervix treated with cCRT. However, no
      clinical associations could be established for p53, p21/waf1/cip1, MIB-1, EGFR,
      and Bcl-2 protein expressions.

PMID- 19101093
TI  - Carcinoembryonic antigen as a predictor of pathologic response and a prognostic
      factor in locally advanced rectal cancer patients treated with preoperative
      chemoradiotherapy and surgery.
AB  - PURPOSE: To evaluate the role of serum carcinoembryonic antigen (CEA) as a
      predictor of response to preoperative chemoradiotherapy (CRT) and prognostic
      factor for rectal cancer. MATERIALS AND METHODS: The study retrospectively
      evaluated 352 locally advanced rectal cancer patients who underwent preoperative
      CRT followed by surgery. Serum CEA levels were determined before CRT
      administration (pre-CRT CEA) and before surgery (post-CRT CEA). Correlations
      between pre-CRT CEA levels and rates of good response (Tumor regression grade
      3/4) were explored. Patients were categorized into three CEA groups according to
      their pre-/post-CRT CEA levels (ng/mL) (Group A: pre-CRT CEA <or= 3; B: pre-CRT
      CEA >3, post-CRT CEA <or=3; C: pre- and post-CRT CEA >3 ng/mL), and their
      oncologic outcomes were compared. RESULTS: Of 352 patients, good responses were
      achieved in 94 patients (26.7%). The rates of good response decreased
      significantly as the pre-CRT CEA levels became more elevated (CEA [ng/mL]: <or=3,
      36.4%; 3-6, 23.6%; 6-9, 15.6%; >9, 7.8%; p < 0.001). The rates of good response
      were significantly higher in Group A than in Groups B and C (36.4% vs. 17.3% and
      14.3%, respectively; p < 0.001). The 3-year disease-free survival rate was
      significantly better in Groups A and B than in Group C (82% and 79% vs. 57%,
      respectively; p = 0.005); the CEA grouping was identified as an independent
      prognostic factor (p = 0.025). CONCLUSIONS: In locally advanced rectal cancer
      patients, CEA levels could be of clinical value as a predictor of response to
      preoperative CRT and as an independent prognostic factor after preoperative CRT
      and curative surgery.

PMID- 19101094
TI  - Postoperative strontium-90 brachytherapy in the prevention of keloids: results
      and prognostic factors.
AB  - PURPOSE: The aim of this study was to evaluate the results of keloidectomy and
      strontium 90 brachytherapy in the prevention of keloid recurrence following
      excision and to identify outcome and the prognostic factors that predict keloid
      recurrence after irradiation. METHODS AND MATERIALS: Data of 612 patients with
      892 keloids treated between 1992 and 2006 were evaluated retrospectively.
      Brachytherapy was performed using a Sr-90Y surface applicator. Total dose was 20
      Gy in 10 fractions. RESULTS: With a median follow-up of 61 months, the overall
      recurrence-free response rate for all keloids was 87.6%. Multivariate analysis
      revealed the following prognostic factors for recurrence: keloid size > 5 cm (p <
      0.0001), burn scars as the keloid etiology (p < 0.0001), and previous treatment
      (p < 0.0001). Outcome was not found to be significantly related to the interval
      between surgery and radiotherapy, sex, or age. Pruritus and skin reddening were
      the most common symptoms of keloids, but all signs and symptoms abated with time
      after treatment. Cosmetic results from the keloid treatment were considered good
      or excellent in 70.6% of the patients. CONCLUSION: Our study findings show that
      excision plus Sr-90 brachytherapy is effective in the eradication of keloids. Sr
      90 radiotherapy (20 Gy in 10 fractions) achieved a similar local control rate, as
      have higher doses per fraction in other series. It also resulted in a good
      cosmetic rate and relief of symptoms. Our data further suggest that the
      initiation of postoperative irradiation within hours of surgical excision is not
      important to therapeutic outcome.

PMID- 19101095
TI  - Differential effects of x-rays and high-energy 56Fe ions on human mesenchymal
      stem cells.
AB  - PURPOSE: Stem cells hold great potential for regenerative medicine, but they have
      also been implicated in cancer and aging. How different kinds of ionizing
      radiation affect stem cell biology remains unexplored. This study was designed to
      compare the biological effects of X-rays and of high-linear energy transfer (LET)
      (56)Fe ions on human mesenchymal stem cells (hMSC). METHODS AND MATERIALS: A
      multi-functional comparison was carried out to investigate the differential
      effects of X-rays and (56)Fe ions on hMSC. The end points included modulation of
      key markers such as p53, cell cycle progression, osteogenic differentiation, and
      pathway and networks through transcriptomic profiling and bioinformatics
      analysis. RESULTS: X-rays and (56)Fe ions differentially inhibited the cell cycle
      progression of hMSC in a p53-dependent manner without impairing their in vitro
      osteogenic differentiation process. Pathway and network analyses revealed that
      cytoskeleton and receptor signaling were uniquely enriched for low-dose (0.1 Gy)
      X-rays. In contrast, DNA/RNA metabolism and cell cycle regulation were enriched
      for high-dose (1 Gy) X-rays and (56)Fe ions, with more significant effects from
      (56)Fe ions. Specifically, DNA replication, DNA strand elongation, and DNA
      binding/transferase activity were perturbed more severely by 1 Gy (56)Fe ions
      than by 1 Gy X-rays, consistent with the significant G2/M arrest for the former
      while not for the latter. CONCLUSIONS: (56)Fe ions exert more significant effects
      on hMSC than X-rays. Since hMSC are the progenitors of osteoblasts in vivo, this
      study provides new mechanistic understandings of the relative health risks
      associated with low- and high-dose X-rays and high-LET space radiation.

PMID- 19101096
TI  - Preoperative [18F]fluorodeoxyglucose positron emission tomography standardized
      uptake value of neck lymph nodes predicts neck cancer control and survival rates
      in patients with oral cavity squamous cell carcinoma and pathologically positive
      lymph nodes.
AB  - PURPOSE: Survival in oral cavity squamous cell carcinoma (OSCC) depends heavily
      on locoregional control. In this prospective study, we sought to investigate
      whether preoperative maximum standardized uptake value of the neck lymph nodes
      (SUVnodal-max) may predict prognosis in OSCC patients. METHODS AND MATERIALS: A
      total of 120 OSCC patients with pathologically positive lymph nodes were
      investigated. All subjects underwent a [18F]fluorodeoxyglucose (FDG) positron
      emission tomography (PET) scan within 2 weeks before radical surgery and neck
      dissection. All patients were followed up for at least 24 months after surgery or
      until death. Postoperative adjuvant therapy was performed in the presence of
      pathologic risk factors. Optimal cutoff values of SUVnodal-max were chosen based
      on 5-year disease-free survival (DFS), disease-specific survival (DSS), and
      overall survival (OS). Independent prognosticators were identified by Cox
      regression analysis. RESULTS: The median follow-up for surviving patients was 41
      months. The optimal cutoff value for SUVnodal-max was 5.7. Multivariate analyses
      identified the following independent predictors of poor outcome: SUVnodal-max
      >or=5.7 for the 5-year neck cancer control rate, distant metastatic rate, DFS,
      DSS, and extracapsular spread (ECS) for the 5-year DSS and OS. Among ECS
      patients, the presence of a SUVnodal-max >or=5.7 identified patients with the
      worst prognosis. CONCLUSION: A SUVnodal-max of 5.7, either alone or in
      combination with ECS, is an independent prognosticator for 5-year neck cancer
      control and survival rates in OSCC patients with pathologically positive lymph
      nodes.

PMID- 19101097
TI  - Magnetic resonance imaging-guided intracavitary brachytherapy for cancer of the
      cervix.
AB  - PURPOSE: To determine the feasibility and benefits of optimized magnetic
      resonance imaging (MRI)-guided brachytherapy (BT) for cancer of the cervix.
      METHODS AND MATERIALS: A total of 20 patients with International Federation of
      Gynecology and Obstetrics Stage IB-IV cervical cancer had an MRI-compatible
      intrauterine BT applicator inserted after external beam radiotherapy. MRI scans
      were acquired, and the gross tumor volume at diagnosis and at BT, the high-risk
      (HR) and intermediate-risk clinical target volume (CTV), and rectal, sigmoid, and
      bladder walls were delineated. Pulsed-dose-rate BT was planned and delivered in a
      conventional manner. Optimized MRI-based plans were developed and compared with
      the conventional plans. RESULTS: The HR CTV and intermediate-risk CTV were
      adequately treated (the percentage of volume treated to >or=100% of the intended
      dose was >95%) in 70% and 85% of the patients with the conventional plans,
      respectively, and in 75% and 95% of the patients with the optimized plans,
      respectively. The minimal dose to the contiguous 2 cm(3) of the rectal, sigmoid,
      and bladder wall volume was 16 +/- 6.2, 25 +/- 8.7, and 31 +/- 9.2 Gy,
      respectively. With MRI-guided BT optimization, it was possible to maintain
      coverage of the HR-CTV and reduce the dose to the normal tissues, especially in
      patients with small tumors at BT. In these patients, the HR percentage of volume
      treated to >or=100% of the intended dose approached 100% in all cases, and the
      minimal dose to the contiguous 2-cm(3) of the rectum, sigmoid, and bladder was 12
      32% less than with conventional BT planning. CONCLUSION: MRI-based BT for
      cervical cancer has the potential to optimize primary tumor dosimetry and reduce
      the dose to critical normal tissues, particularly in patients with small tumors.

PMID- 19101098
TI  - Promoting abstinence from cocaine and heroin with a methadone dose increase and a
      novel contingency.
AB  - To test whether a combination of contingency management and methadone dose
      increase would promote abstinence from heroin and cocaine, we conducted a
      randomized controlled trial using a 2 x 3 (dosexcontingency) factorial design in
      which dose assignment was double-blind. Participants were 252 heroin- and cocaine
      abusing outpatients on methadone maintenance. They were randomly assigned to
      methadone dose (70 or 100mg/day, double-blind) and voucher condition
      (noncontingent, contingent on cocaine-negative urines, or "split"). The "split"
      contingency was a novel contingency that reinforced abstinence from either drug
      while doubly reinforcing simultaneous abstinence from both: the total value of
      incentives was "split" between drugs to contain costs. The main outcome measures
      were percentages of urine specimens negative for heroin, cocaine, and both
      simultaneously; these were monitored during a 5-week baseline of standard
      treatment (to determine study eligibility), a 12-week intervention, and a 10-week
      maintenance phase (to examine intervention effects in return-to-baseline
      conditions). DSM-IV criteria for ongoing drug dependence were assessed at study
      exit. Urine-screen results showed that the methadone dose increase reduced heroin
      use but not cocaine use. The split 100mg group was the only group to achieve a
      longer duration of simultaneous negatives than its same-dose noncontingent
      control group. The frequency of DSM-IV opiate and cocaine dependence diagnoses
      decreased in the active intervention groups. For a split contingency to promote
      simultaneous abstinence from cocaine and heroin, a relatively high dose of
      methadone appears necessary but not sufficient; an increase in overall incentive
      amount may also be required.

PMID- 19101099
TI  - Motivation Enhancement Therapy with pregnant substance-abusing women: does
      baseline motivation moderate efficacy?
AB  - Some evidence suggests that motivational approaches are less efficacious--or even
      counter-productive--with persons who are relatively motivated at baseline. The
      present study was conducted to examine whether disordinal moderation by baseline
      motivation could partially explain negative findings in a previous study
      [Winhusen, T., Kropp, F., Babcock, D., Hague, D., Erickson, S.J., Renz, C., Rau,
      L., Lewis, D., Leimberger, J., Somoza, E., 2008. Motivational enhancement therapy
      to improve treatment utilization and outcome in pregnant substance users. J.
      Subst. Abuse Treat. 35, 161-173]. Analyses also focused on the relative utility
      of the University of Rhode Island Change Assessment (URICA) scale, vs. a single
      goal question as potential moderators of Motivation Enhancement Therapy (MET).
      Participants were 200 pregnant women presenting for substance abuse treatment at
      one of four sites. Women were randomly assigned to either a three-session MET
      condition or treatment as usual (TAU). Generalized Estimating Equations (GEE)
      revealed no significant moderation effects on drug use at post-treatment. At
      follow-up, contrary to expectations, participants who had not set a clear quit
      goal at baseline were less likely to be drug-free if randomized to MET (OR=0.48);
      participants who did set a clear quit goal were more likely to be drug-free if
      randomized to MET (OR=2.53). No moderating effects were identified via the URICA.
      Disordinal moderation of MET efficacy by baseline motivation may have contributed
      somewhat to the negative results of the [Winhusen, T., Kropp, F., Babcock, D.,
      Hague, D., Erickson, S.J., Renz, C., Rau, L., Lewis, D., Leimberger, J., Somoza,
      E., 2008. Motivational enhancement therapy to improve treatment utilization and
      outcome in pregnant substance users. J. Subst. Abuse Treat. 35, 161-173] study,
      but in the opposite direction expected. A simple question regarding intent to
      quit may be useful in identifying persons who may differentially respond to
      motivational interventions. However, moderation effects are unstable, may be best
      identified with alternate methodologies, and may operate differently among
      pregnant women.

PMID- 19101101
TI  - Characterization of Dutch Staphylococcus aureus from bovine mastitis using a
      Multiple Locus Variable Number Tandem Repeat Analysis.
AB  - Current typing methods for Staphylococcus aureus have important drawbacks. We
      evaluated a Multiple Locus Variable Number Tandem Repeat Analysis (MLVA) scheme
      with 6 loci which lacks most drawbacks on 85 bovine mastitis isolates from The
      Netherlands. For each locus the number of repeat units (RU) was calculated. Each
      combination of repeat units was assigned a MLVA-type (MT). We compared the MLVA
      typing result with Multi Locus Sequence Typing (MLST), spa-typing and Pulsed
      Field Gel Electrophoresis (PFGE). MLVA typing resulted in 18 MTs, although 3 loci
      could not always be amplified. Spa-typing distinguished 10 spa-types including 3
      dominant and 2 new types. PFGE showed 5 dominant profiles with 15 related
      profiles and 6 unique profiles. MLST showed 4 dominant STs. Some types appeared
      to be bovine specific. The Simpson's Indices of diversity for PFGE, MLST, spa
      typing and MLVA were 0.887, 0.831, 0.69 and 0.781, respectively, indicating that
      discriminatory power of MLVA was between MLST and spa-typing, whereas PFGE
      displayed the highest discriminatory power. However, MLVA is fast and cheap when
      compared to the other methods. The Adjusted Rand index and Wallace's coefficient
      indicated that MLVA was highly predictive for spa-type, but not vice versa.
      Analysis of the region neighboring SIRU05 showed a difference in the genetic
      element bordering the repeats of SIRU05 that explained the negative SIRU05 PCRs.
      PFGE, MLST, and MLVA are adequate typing methods for bovine-associated S. aureus.

PMID- 19101100
TI  - Familial and non-familial smoking: effects on smoking and nicotine dependence.
AB  - BACKGROUND: This study examined the relative impact of familial and non-familial
      smoking on participant smoking and nicotine dependence. METHODS: This is a
      longitudinal study of 838 African American and Puerto Rican participants who were
      interviewed four times in their homes over a 15-16-year period (1990, 1994-1996,
      2000-2001, and 2004-2006). RESULTS: Parental smoking during adolescence had a
      direct positive path to peer smoking during adolescence, which in turn had a
      direct positive path to participant smoking during the mid-twenties. In addition
      to the direct path between participant smoking in the mid-twenties and
      participant nicotine dependence during the late twenties, there was an indirect
      effect mediated by the partner's problems resulting from smoking during the late
      twenties. CONCLUSIONS: This research demonstrates the key role the social
      environment plays in smoking and nicotine dependence. Both familial and non
      familial smoking were significantly related to smoking and nicotine dependence.
      Public health implications suggest the importance of targeting prevention and
      treatment policies based on the participants' stage of development. During
      adolescence the focus should be on parental and peer smoking, whereas during the
      twenties attention might be paid to their own smoking and that of their partners.

PMID- 19101102
TI  - [Endovascular aneurysm repair follow-up by unenhanced and contrast-enhanced
      duplex ultrasound].
AB  - OBJECTIVE: Long-term surveillance is needed after endovascular aneurysm repair to
      monitor the aneurysm and search for persistent endoleaks. Our aim was to compare
      follow-up with duplex ultrasound, with and without a new contrast agent to track
      endoleaks, versus computed tomography angiography taken as the gold standard.
      MATERIAL AND METHOD: Patients treated with endograft were included prospectively
      from December 2005 to July 2006. Aortic duplex ultrasound and computed tomography
      were used to measure maximal aneurysm diameter and detect endoleaks. Patients
      with a high risk of endoleaks had a contrast-enhanced ultrasound with Sonovue
      (Bracco, Milan, Italy). We compared echographic and tomographic diameter and
      studied the sensitivity of ultrasound endoleak diagnosis. RESULTS: Sixty-seven
      patients were included. There was a good correlation between maximum
      anteroposterior diameters (CCI=0.98) measured by ultrasound and tomography, as
      well as mean maximum cross section diameters (CCI=0.96). Compared to tomography,
      the sensitivity of ultrasound endoleaks diagnosis was 44% (kappa=0.58). Contrast
      injection improved this sensitivity significantly (p<0.001) (sensitivity=88%;
      kappa=0.72). CONCLUSION: These findings confirmed the performance of our
      ultrasound method for endograft surveillance. Contrast-enhanced ultrasound
      significantly improves the sensitivity of detection of endoleaks. We suggest
      alternating ultrasound and tomographic exams. A unique report chart for use
      nationwide would be useful for standardizing follow-up.

PMID- 19101103
TI  - Crohn's disease lymphadenopathy: MR imaging findings.
AB  - PURPOSE: To assess mesenteric lymph nodes in patients with different Crohn's
      disease subtypes identified on MR Enteroclysis. MATERIALS AND METHODS: Thirty
      four patients, categorized into three different Crohn's disease subgroups,
      underwent MR Enteroclysis. A high resolution coronal true FISP sequence with fat
      saturation was applied to assess mesenteric lymph node anatomic distribution,
      size and shape. Their enhancement ratio (ER) was calculated by dividing signal
      intensity of each node to signal intensity of nearby vessel on T1 weighted FLASH
      images, acquired 75 s after intravenous administration of gadolinium. A one-way
      analysis of variance statistical test was applied to investigate any significant
      differences regarding mean ER among different disease subgroups. RESULTS: Two
      hundred and eighty-three mesenteric lymph nodes were assessed, 231 in patients
      with active inflammatory (AI) disease, 36 in patients with fibrostenotic (FS) and
      16 in patients with fistulizing/perforating (FP) disease. Maximum and minimum
      diameters were 3.2 and 0.3 cm, respectively. 75% of the lymph nodes presented
      with an oval shape. The majority were identified as being ileocolic (34%) and
      paracolic (31%). AI subgroup lymph nodes presented with the highest mean ER
      (0.783+/-0.17) followed by FP (0.706+/-0.1) and FS subgroup (0.652+/-0.17) lymph
      nodes. The differences in mean values of ER of mesenteric lymph nodes between AI
      and FS subtypes were statistically significant (p<0.0001), while mean ER between
      nodes of FP and the other two subtypes did not present statistically significant
      differences. CONCLUSION: ER of mesenteric lymph nodes identified on MR
      Enteroclysis may vary across different subtypes of Crohn's disease. Such
      differences may be valuable in clinical practice.

PMID- 19101104
TI  - (18)F-FDG-PET/CT of orofacial tumors, a value of whole-body imaging approach.
AB  - AIM: Staging of head and neck tumors is one of the most difficult tasks in
      imaging techniques, due to the very complicated head and neck anatomy and serious
      problems with the differentiation of reactive enlarged lymph nodes and lymph
      nodes involved with metastases. The aim of the study was to evaluate the validity
      of the whole-body approach in the assessment of head and neck malignancies using
      (18)F-FDG-PET/CT. MATERIALS AND METHODS: The analysis of a group of 1750
      consecutive whole-body procedures in all indications of (18)F-FDG-PET/CT was made
      according to: the presence of orofacial tumors; their histology; findings
      concerning the spread outside head and neck region; and findings concerning the
      primary staging or restaging. The examinations of head and neck tumors were
      performed after intravenous application of the (18)F-FDG and its accumulation for
      one hour. Drinking and speaking is restricted during this accumulation to prevent
      artificial muscle (18)F-FDG uptake and to minimize false positive findings. In
      our hospital, high resolution PET is followed by the sub-millimeter isotropic
      acquisition of CT data after intravenous application of an iodinated contrast
      material. The acquisitions of head and neck region and trunk are performed
      separately to obtain optimal resolution in both regions. RESULTS: 105
      examinations of the orofacial tumors were performed on 87 patients in a group of
      1750 consecutive PET/CT examinations. The ratio between primary staging and
      restaging was 3:7. The most frequent indications were carcinomas of the tongue
      (19 examinations) and carcinomas of the salivary glands (19 examinations). The
      metastatic spread of the tumor outside the region of the head and neck was noted
      in 12 cases. CONCLUSION: Our findings of distant metastases confirmed the
      importance of the use of whole-body PET/CT in this indication.

PMID- 19101105
TI  - The value of brain CT findings in acute methanol toxicity.
AB  - OBJECTIVE: Due to depressant effects of methanol on the central nervous system,
      brain computed tomography (CT) scan has been introduced as a diagnostic device in
      methanol intoxication. The authors aimed to present brain CT findings in patients
      with acute methanol intoxication and to determine signs associated with death.
      MATERIALS AND METHODS: This cohort study involved 42 consecutive patients with
      acute methanol intoxication. Inclusion criteria were consisted of characteristic
      clinical presentation of methanol poisoning, and metabolic acidosis with
      increased anion and osmolar gaps. Brain CT scans without contrast medium were
      obtained. To determine the association between the CT findings and death, the chi
      square test or the Fisher's exact test, odds ratio (OR) and its 95% confidence
      interval (95% CI) were calculated. RESULTS: Twenty-eight patients (66.6%) had a
      total of 55 abnormal findings on brain CT, in which bilateral putaminal hypodense
      lesions was the most common manifestation (27 cases, 96.4%). Putaminal hemorrhage
      with varying degrees was observed in 7 patients (25%). Six patients (21.4%) had
      low attenuation lesions in the subcortical white matter of the insula. A
      significant association was observed between putaminal hemorrhage (OR=8, 95%
      CI=1.187-53.93, P=0.018) and subcortical necrosis of the insula (OR=11, 95%
      CI=1.504-80.426, P=0.007) with death. CONCLUSION: In addition to clinical and
      laboratory findings, presence of putaminal hemorrhage and insular subcortex white
      matter necrosis are associated with a poor clinical outcome in patients with
      methanol poisoning.

PMID- 19101106
TI  - Post-treatment complications of soft tissue tumours.
AB  - PURPOSE: To identify local and distant complications of patients with soft tissue
      tumours and evaluate their relationships to types of therapy. METHODS AND
      MATERIALS: Fifty-one patients (29 males and 22 females, ages 14-80 years) with 34
      malignant and 17 benign soft tissue tumours were evaluated for local and distant
      complications after resection or amputation only (26 patients) or after the
      addition of radiotherapy (25 patients: 17 patients had external beam therapy, 7
      patients had external beam therapy and brachytherapy, and one patient had
      extracorporeal irradiation and reimplantation). Duration of follow-up averaged
      3.75 years for malignant tumours and 2.79 years for benign tumours. Follow-up
      studies included radiography, T1- and T2-weighted magnetic resonance (MR)
      imaging, dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI), computed
      tomography for thoracic and abdominal metastases, and 3-phase technetium-99m
      labeled-methylene-diphosphonate scintigraphy for bone metastases. RESULTS:
      Recurrent tumours were 2.2 times more frequent in patients who had undergone
      their initial resection at an outside hospital as compared with those first
      treated at the university hospital. Nine of 11 recurrences occurred after
      marginal surgery. Metastases from soft tissue sarcomas, most commonly to lung
      (nine patients) and to bone and muscle (five patients), showed no specific
      relationship to type of therapy. DCE-MRI differentiated rapidly enhancing soft
      tissue recurrences (11 patients) and residual tumours (6 patients) from slowly
      enhancing muscle inflammation, and non-enhancing fibrosis and seromas that
      usually did not enhance. Seromas developed in 76% of patients who had
      postoperative radiation therapy and in 7.7% of patients who had only surgery.
      Subcutaneous and cutaneous oedema and muscle inflammation was at least four times
      more frequent after adjunct radiotherapy than after resection alone. Irrespective
      of the type of treatment, inflammatory changes in muscle and subcutaneous and
      cutaneous tissue and the majority of seromas were evident at the first follow-up
      study. Although seromas after resection and external beam therapy resolved with
      time, seromas after additional brachytherapy persisted. Inflammatory changes in
      muscle and cutaneous and subcutaneous tissue after resection alone disappeared by
      the second follow-up study, whereas these changes after radiotherapy resolved
      months to years after treatment. Fourteen of 51 patients showed MR findings of
      chronic muscular atrophy, predominantly located in the lower extremity.
      Heterotopic ossification was seen in three patients after resection and
      amputation without radiotherapy. Except for one patient with aggressive
      fibromatosis, bone and nerve complications occurred in patients with soft tissue
      malignancy. Twelve patients had osteoporosis. Six patients sustained fractures in
      irradiated osteoporotic bone of the lower extremity, and one patient had a
      vertebral fracture in radiographically normal but irradiated bone. In addition,
      one patient was found to have a medullary infarct in an irradiated femur. In
      nerve entrapment, DCE-MRI demonstrated the rapidly enhancing recurrent tumour or
      non-enhancing fibrosis surrounding the slowly enhancing nerve. T1- and T2
      weighted MR images displayed the acute and chronic sequelae of nerve entrapment
      and nerve transection with denervation as T2-hyperintense acute muscle atrophy or
      T1-hypertense chronic fatty muscular atrophy with decrease in muscle volume.
      CONCLUSION: This study suggests a possible relationship between types of
      treatment of soft tissue tumours and subsequent complications. Postoperative
      radiotherapy was associated with a significant number of patients with seromas,
      muscle, cutaneous and subcutaneous inflammation, and fractures. Incomplete or
      difficult surgery resulted in residual or recurrent tumours and heterotopic
      ossification. Muscle atrophy and nerve entrapment were related to both treatments
      (resection alone or radiotherapy after resection). Diligent follow-up of patients
      with soft tissue tumours with recognition of these complications and their
      differentiation from recurrent or residual tumour can help guide clinical care
      and may negate the need for surgery when benign disease is defined.

PMID- 19101107
TI  - Serum levels of stanniocalcin-1 in Holstein heifers and cows.
AB  - Stanniocalcin-1 is a hormone that possesses both paracrine and endocrine
      functions and has recently been identified in mammals. While paracrine functions
      have been determined for several organs, the role of circulating stanniocalcin-1
      in cattle is still unclear but, observations in mice and cows suggest that
      stanniocalcin-1 plays a role in both gestation and lactation. The changes in
      serum stanniocalcin-1 content in different physiological states have never been
      evaluated in ruminants. We measured stanniocalcin-1 levels in sera from cattle
      ranging in age from post-weaned calves to 17-month-old heifers and in sera from
      cows during lactation and pregnancy. Our results indicate that the blood
      concentration of stanniocalcin-1 is increased by pregnancy, but not by lactation.
      The highest levels of stanniocalcin-1 were found in young calves and during the
      non-lactating period preceding calving. This suggests that stanniocalcin-1 is
      important for gestation and the preparation of the mammary gland for lactation.

PMID- 19101108
TI  - [When an antibiotic becomes toxic].

PMID- 19101109
TI  - [Labour epidural analgesia for a woman with a factor XI deficiency: an
      illconsidered risk?].
AB  - Inherited bleeding disorders contraindicate epidural analgesia because of the
      risk of epidural haematoma. However, there is no consensus about a minimal rate
      of factor XI required for its performance. We report here a case of epidural
      analgesia in a pregnant woman with a moderate and symptomatic factor XI
      deficiency, despite this theoretical contraindication. Indeed, the factor XI
      deficiency results in a haemorrhagic risk which is variable and not easily
      foreseeable. Nevertheless, no neurological after-effect or excessive bleeding
      occurred although no specific prophylaxis had been performed.

PMID- 19101110
TI  - [The seventh report of the confidential enquiries into maternal deaths in the
      United Kingdom: comparison with French data].
AB  - OBJECTIVES: To describe the main results and recommendations from the seventh
      report on confidential enquiry into maternal death in the United Kingdom (UK)
      (2003-2005). METHODS: Comparison with the most recent French data (1999-2001).
      RESULTS: Maternal mortality tends to increase and indirect causes are more common
      than direct causes. Causes of deaths and their respective ranking are strikingly
      different with what is observed in France. This can probably be ascribed to the
      increasing role of obesity, maternal age, tobacco use and diabetes in the UK.
      Cardiac disease now ranks first among indirect causes and is linked in half of
      cases to ischaemic heart disease. This contrasts with the French situation where
      cardiac death remains rare. Thromboembolic disease remains the main cause of
      direct deaths while the role of haemorrhage has decreased. This also contrasts
      with the French situation where haemorrhage remains of concern. Sepsis is now the
      second cause in the UK (at the same level than preeclampsia), while it is a rare
      cause in France. In both French and UK reports, substandard care remains of
      concern in many cases of direct deaths. Anaesthesia is now a rare cause of death
      (n=6) although the UK report emphasizes that in a large number of cases,
      anaesthesia has contributed to death because of substandard care (n=31). In many
      cases, the report highlights the deleterious role of unsupervised residents.
      CONCLUSION: The United Kingdom report integrates modern strategies that might
      improve patient safety, including systems failure analysis, incident reporting
      and registries. Systematic auditing (with proposition of auditable standards)
      might also prove important in facilitating implementation of the top ten
      recommendations. All these strategies might also be implemented in France and
      hopefully might prove to be also beneficial here.

PMID- 19101111
TI  - Effects of balloon valvuloplasty on coronary blood flow in neonates with critical
      pulmonary valve stenosis assessed with transthoracic Doppler echocardiography.
AB  - BACKGROUND: Treating pulmonary valve stenosis with balloon valvuloplasty (BV) is
      a good model to study the effect of right ventricular (RV) pressures on coronary
      flow. METHODS: Transthoracic Doppler echocardiography was used to register
      coronary flow in 10 age-matched healthy controls and 7 neonates before and 1 day
      after BV. RESULTS: Left ventricular fractional shortening and cardiac output
      increased significantly after BV. Right coronary artery diameter decreased from
      1.2 +/- 0.2 to 1.1 +/- 0.1 mm (P < .02). Posterior descending coronary artery
      flow parameters decreased significantly, with blood flow decreasing from 8.4 to
      5.7 +/- 1.9 mL/s (P < .003). RV end-diastolic pressure and RV systolic pressure
      explained almost totally the variation in coronary flow (r(2) = 0.87).
      CONCLUSIONS: RV end-diastolic pressure and RV systolic pressure determined
      coronary flow in neonates with critical pulmonary valve stenosis. Cardiac output
      and left ventricular fractional shortening increased after pulmonary valve BV.

PMID- 19101112
TI  - Quantification of left ventricular systolic dyssynchrony by real-time three
      dimensional echocardiography.
AB  - OBJECTIVE: To assess real-time 3-dimensional echocardiography (RT3DE)-derived
      left ventricular (LV) systolic dyssynchrony parameters: (1) normal values, (2)
      characteristics in patients with heart failure (HF) and a wide or narrow QRS
      complex, (3) interobserver and intraobserver variability with current state of
      the art RT3DE hardware and software technology, and (4) incremental value in
      patients with HF who receive cardiac resynchronization therapy (CRT). METHODS:
      The study involved 84 patients with HF (mean age 54 +/- 15 years, 50 men) and 60
      healthy volunteers (mean age 41 +/- 15 years, 36 men). Semiautomated LV
      endocardial border tracking was used to calculate regional time-to-minimum
      systolic volume and to generate parametric maps and the systolic dyssynchrony
      index (SDI), defined as the standard deviation of time-to-minimum systolic volume
      of the 16 LV segments expressed in percentage of R-R duration. RESULTS: The
      volume rate of the RT3DE datasets in patients with HF was 31 +/- 9 Hz (range 15
      42 Hz). The normal value of the SDI was 4.1% +/- 2.2% (range <1.0%-8.9%).
      Patients with HF had a larger SDI (13.4% +/- 8.1%, P < .001). There was only a
      weak correlation (r2 = 0.07, P < .05) between the QRS duration and the SDI.
      Interobserver interclass correlation and variability of the SDI depended on image
      quality (good: 0.993 and 9%, moderate: 0.907 and 16%, respectively).
      Interobserver agreement for the identification of the most delayed LV segment
      depended on image quality (good: 90%, moderate: 76%). Thirty-nine patients
      underwent CRT. At the 12-month follow-up, LV volumetric responders had a
      significant reduction in the SDI (16.3% +/- 3.3% to 7.7% +/- 2.4%, P < .001).
      CONCLUSION: With state of the art technology, RT3DE allows reproducible
      assessment of LV systolic dyssynchrony, which may be useful to identify potential
      responders to CRT.

PMID- 19101113
TI  - Relations between systolic and diastolic function in children with dilated and
      hypertrophic cardiomyopathy as assessed by tissue Doppler imaging.
AB  - BACKGROUND: The aim of this study was to investigate relations between
      longitudinal peak systolic tissue velocity (S') and early diastolic tissue
      velocity (E') in children with dilated cardiomyopathy (DCM) and hypertrophic
      cardiomyopathy (HCM). METHODS: S' and E' were recorded by tissue Doppler at the
      lateral (mitral) annulus and basal ventricular septum in 148 children (age range,
      0-18 years), 34 with DCM, 60 with HCM, and 54 controls. Correlations between S'
      and E' and the S'/E' ratio were investigated, as well as relations to other
      functional indices. RESULTS: In all groups, S' was correlated with E' at the
      lateral annulus and interventricular septum, but the relation and S'/E' ratio
      differed between groups. In patients with DCM, both S' and E' were decreased,
      whereas in those with HCM, E' was decreased, with smaller decreases in S'. The
      S'/E' ratio was correlated with indices of ventricular relaxation and filling.
      CONCLUSIONS: In pediatric DCM and HCM, systolic and diastolic longitudinal
      function are related, possibly reflecting effects of systolic function on
      diastolic recoil.

PMID- 19101114
TI  - Hepatic IL-17 responses in human and murine primary biliary cirrhosis.
AB  - The emergence of new regulatory and pro-inflammatory immune cell subsets and
      cytokines dictates the need to re-examine the role of these subsets in various
      diseases involving the immune system. IL-17 has been recently identified as a key
      cytokine involved in numerous autoimmune processes. However, its role in liver
      autoimmune diseases remains unclear. Primary biliary cirrhosis (PBC) is
      characterized histologically by autoreactive CD4 and CD8 T cells surrounding
      damaged bile ducts. CD4(+) T cells are a major source of IL-17, which compose a
      distinct T helper subset (Th17). Thus we set out to determine the role of IL-17
      in both human and a murine model of PBC in a liver-targeted manner. Our data
      demonstrate an increase in the frequency of IL-17(+) lymphocytic infiltration in
      liver tissues from PBC patients and those with other liver dysfunctions as
      compared to healthy livers. IL-2 receptor alpha knockout mice, a recently
      identified murine model of human PBC, also demonstrate marked aggregations of IL
      17-positive cells within portal tracts and increased frequencies of Th17 cells in
      the liver compared to the periphery. Interestingly, CD4(+) T cells from livers of
      normal C57BL/6J mice also secreted higher levels of IL-17 relative to those from
      spleens, indicating a preferential induction of Th17 cells in liver tissues.
      Importantly, C57BL/6J cocultures of splenic CD4(+) T cells and liver non
      parenchymal cells increased IL-17 production approximately 10-fold compared to T
      cells alone, suggesting a role of the liver microenvironment in Th17 induction in
      cases of liver autoimmunity and other liver inflammatory diseases.

PMID- 19101116
TI  - Nutritional risk and health care use before and after an acute hospitalization
      among the elderly.
AB  - OBJECTIVE: Our objective was to assess the nutritional status and health care use
      of community-dwelling elderly before hospitalization and determine risk factors
      for longer hospitalizations during 3 mo of follow-up. METHODS: During a 1-y
      period, we recruited patients 65 y and older admitted to an internal medicine
      ward at Soroka Medical Center (Beer-Sheva, Israel). Data were obtained regarding
      health and nutritional status and demographic and social characteristics. We
      assessed the utilization of health care services during a follow-up period of 3
      mo. RESULTS: Seventy-nine of 204 patients (38.7%) were at nutritional risk.
      Patients at nutritional risk were older (P < 0.001) and less educated (P = 0.03)
      than the well-nourished group. Nutritional risk was associated with more
      diagnosed diseases, days of hospital stay, and physician visits before admission.
      Participants hospitalized for more than 6 d were significantly less educated,
      with lower cognitive, functional, Mini Nutritional Assessment, and Nutritional
      Risk Index scores and a significantly higher depressive symptoms score.
      Functional status and sum of nutritional problems were significant predictors of
      length of hospitalization in the following 3 mo. CONCLUSION: Nutritional risk is
      a source of concern for health care providers and services, because it
      significantly increases risk of hospital admission and length of stay. It is
      important to increase the awareness of primary care providers to the impact of
      nutrition on health care use and provide appropriate tools to screen and treat
      nutritional problems.

PMID- 19101115
TI  - A casein diet added isoflavone-enriched soy protein favorably affects biomarkers
      of steatohepatitis in obese Zucker rats.
AB  - OBJECTIVE: Dietary supplementation of a soy protein enriched with isoflavones
      (HDI) has been shown to improve fatty liver in obese rats. The main objective of
      this study was to investigate whether HDI would influence the inflammatory status
      in livers of obese rats with fatty liver. METHODS: Male obese Zucker fa/fa rats
      were fed casein (controls) or casein supplemented with HDI (containing 4.00 g of
      genistein and 4.50 g of daidzein per kilogram of diet) for 6 wk. RESULTS: The HDI
      fed rats had a markedly lower hepatic concentration of triacylglycerol when
      compared with controls. The decreased aspartate transaminase/alanine transaminase
      ratio in plasma, together with lower circulating levels of alkaline phosphatase
      and bile acids after HDI feeding, implied an improved hepatitis. This was
      supported by decreased plasma and hepatic mRNA levels of tumor necrosis factor
      alpha, lower plasma levels of interleukin-1beta and monocyte chemoattractant
      protein-1, and an increased anti-inflammatory fatty acid index in plasma. HDI
      also seemed to protect the rats from oxidative damage, because the level of lipid
      peroxides in triacylglycerol-rich lipoproteins after in vitro copper oxidation
      was lower for HDI-fed rats when compared with controls. CONCLUSION: These results
      show that isoflavone-enriched soy protein favorably affects biomarkers of hepatic
      inflammation in obese Zucker fa/fa rats with fatty liver. Thus, dietary soy
      proteins enriched in isoflavones may be a promising agent to improve
      steatohepatitis in patients.

PMID- 19101117
TI  - Modular endoprosthesis for mandibular body reconstruction: a clinical, micro-CT
      and histologic evaluation in eight Macaca fascicularis.
AB  - This paper presents the results of an animal experiment, in which a modular
      endoprosthesis is tested to replace a resected part of the mandible. The
      prostheses were fixed with polymethacrylate (PMMA) cement into the medullar space
      of the stumps. Clinical, radiologic, micro-computed tomographic and histologic
      evaluations were made after 3 and 6 months on four Macaca fascicularis for each
      implantation time. The prosthesis had not loosened but there were some loose
      screws that had caused fistulas in three animals. The stems of the modules were
      stably fixed with PMMA cement, surrounded by a fibrous capsule with inflammatory
      cells. This capsule was thinner in the 6-month group and showed less inflammatory
      infiltrate compared with the 3-month group; this was not statistically
      significant. There was an increase in woven bone surrounding the modules after 6
      months. After 3 months of implantation, there was a considerable inflammatory
      reaction in the soft tissues surrounding the module, which subsided over
      following 3 months. The results are encouraging, but a longer period of follow-up
      is required to assess its application in a clinical setting, and some design
      drawbacks need to be addressed.

PMID- 19101118
TI  - Mucous cell differentiation in a unicystic ameloblastoma.
AB  - The authors report a case of unicystic ameloblastoma with mucous cell
      differentiation in the right mandible of a 24-year-old Korean male who suffered
      from painful swelling for 2 months. A radiograph showed a well-circumscribed
      radiolucent lesion between the root of the right first premolar and the first
      molar tooth. Microscopic examination revealed the cystic lesion was lined with
      ameloblastic epithelium and goblet cells in the epithelium. The mucous cells
      reacted positively to mucicarmine stain. The possible pathogenic mechanism of
      this case reflects the pluripotential character of the odontogenic epithelium.
      The prognosis is probably that expected for conventional unicystic ameloblastoma.

PMID- 19101119
TI  - Sexual differentiation of cortical spreading depression propagation after acute
      and kindled audiogenic seizures in the Wistar audiogenic rat (WAR).
AB  - SUMMARY: Brain excitability diseases like epilepsy constitute one factor that
      influences brain electrophysiological features. Cortical spreading depression
      (CSD) is a phenomenon that can be altered by changes in brain excitability. CSD
      propagation was presently characterized in adult male and female rats from a
      normal Wistar strain and from a genetically audiogenic seizure-prone strain, the
      Wistar audiogenic rat (WAR), both previously submitted (RAS(+)), or not (RAS(-)),
      to repetitive acoustic stimulation, to provoke audiogenic kindling in the WAR
      strain. A gender-specific change in CSD-propagation was found. Compared to
      seizure-resistant animals, in the RAS(-) condition, male and female WARs,
      respectively, presented CSD-propagation impairment and facilitation,
      characterized, respectively, by lower and higher propagation velocities (P<0.05).
      In contraposition, in the RAS(+) condition, male and female WARs displayed,
      respectively, higher and lower CSD-propagation rates, as compared to the
      corresponding controls. In some Wistar and WAR females, we determined estrous
      cycle status on the day of the CSD-recording as being either estrous or
      diestrous; no cycle-phase-related differences in CSD-propagation velocities were
      detected. In contrast to other epilepsy models, such as Status Epilepticus
      induced by pilocarpine, despite the CSD-velocity reduction, in no case was CSD
      propagation blocked in WARs. The results suggest a gender-related, estrous cycle
      phase-independent modification in the CSD-susceptibility of WAR rats, both in the
      RAS(+) and RAS(-) situation.

PMID- 19101120
TI  - Cancer mortality amongst people with epilepsy: a study of two cohorts with severe
      and presumed milder epilepsy.
AB  - BACKGROUND: People with epilepsy may experience an altered pattern of mortality
      due to cancer. We determined cancer mortality in two distinct populations with
      epilepsy: (i) an institutionalised cohort with severe epilepsy (SEC) and (ii)
      another cohort with presumed milder epilepsy (MEC). METHODS: Mortality data from
      1977 until 2003 were obtained for the two cohorts (SEC, n=1358 and MEC, n=4494).
      Standardised mortality ratios (SMRs) for all causes, all cancers and specific
      cancer sites were calculated. FINDINGS: The SMR for all cancers was significantly
      elevated in the SEC (SMR: 1.42; 95%CI: 1.18-1.69) but not in the MEC (SMR: 0.93;
      95%CI: 0.84-1.03). The SMR for brain and CNS neoplasms was significantly elevated
      in the MEC; most cancer deaths in younger ages (<45 years) in this cohort were
      due to brain and CNS neoplasms. There was also a deficit in deaths due to lung
      cancer (SMR: 0.68; 95%CI: 0.54-0.84) in this cohort. In the SEC, SMRs for
      oesophageal (SMR: 2.81, 95%CI: 1.35-5.17), liver (SMR: 4.12, 95%CI: 1.12-10.56)
      and gall bladder (SMR: 7.32, 95%CI: 1.51-21.38) cancers and non-Hodgkin's
      lymphoma (SMR: 2.67, 95%CI: 0.98-5.80) were elevated. CONCLUSIONS: The modest
      excess of all cancer deaths and large excesses of deaths due to cancers at
      certain sites in the SEC and the lack thereof in the MEC suggests dissimilarity
      in the risk factor profile of the two populations. These risk factors, whether
      life style attributes or antiepileptic drugs, need to be identified.

PMID- 19101121
TI  - Utility of subtraction ictal SPECT images in detecting focal leading activity and
      understanding the pathophysiology of spasms in patients with West syndrome.
AB  - PURPOSES: The aims of the study were to evaluate the detectability of focal
      leading activity in three cases of West syndrome having focal abnormal activity
      on EEG by comparing subtraction ictal images and raw ictal images, and to
      interpret the results in 16 cases. METHODS: Subtraction images were constructed
      using iNeurostat (revision 2). RESULTS: In three cases with focal abnormal
      activity on EEG, subtraction ictal images reflected the EEG findings; in
      contrast, raw ictal images did not. Diverse degrees of cortical hyperperfusion,
      ranging from zero to 10 sites, seen in the other 13 cases seemed to reflect spasm
      pathophysiology and rapid spasm propagation. Subtraction ictal images also
      allowed the ready detection of hyperperfusion of subcortical structures and of a
      tight cortico-subcortical relationship in a subset of cases. CONCLUSIONS: We
      showed the superiority of subtraction ictal images in detecting the focal
      epileptic region and in showing propagation pathways from the cortex to
      subcortical structures. A subset of spasms in WS may be focal cortical-onset
      secondarily generalized seizures. We believe that subtraction analysis is
      valuable in patients with complex WS who have partial seizures and spasms
      simultaneously along with focal epileptic EEG activity, as they will likely be
      candidates for epilepsy surgery.

PMID- 19101122
TI  - The relationship between interview-based schizotypal personality dimension scores
      and the continuous performance test.
AB  - The existing research that has examined cognitive performance in samples with
      subclinical schizotypal personality features has been largely limited to
      psychometric self-report questionnaires, which may be biased by distorted self
      awareness of symptoms. The present study examined the relationship between
      performance on a degraded-AX continuous performance test (CPT) and continuous
      dimension scores created from a structured clinical interview for schizotypal
      personality disorder (SPD), which reflected both the breadth and severity of
      schizotypal personality symptoms, in 52 undergraduate students. Only one
      participant met full diagnostic criteria for SPD. The overall dimension score
      from the SPD clinical interview showed a positive correlation with both omission
      (r(s)=.47) and false alarm (r(s)=.41) errors on the CPT. Interpersonal symptoms
      were positively correlated with omission errors (r(s)=.47), while Disorganized
      symptoms were positively correlated with false alarm errors (r(s)=.40). Results
      suggest that higher SPD interview-based dimension scores are associated with
      lower levels of performance on the CPT, even when examining a relatively
      subclinical sample of young adults. In contrast, scores from the psychometric
      Abbreviated Schizotypal Personality Questionnaire in the same sample did not
      correlate with accuracy measures on the CPT, suggesting that the interview-based
      measure of schizotypal personality may have a stronger relationship with CPT
      accuracy. Findings also add to a growing literature suggesting that Interpersonal
      SPD symptoms are primarily related to omission errors, while Disorganized SPD
      symptoms are primarily related to false alarm errors.

PMID- 19101123
TI  - Oral antimicrobial options for the treatment of skin and soft-tissue infections
      caused by methicillin-resistant Staphylococcus aureus (MRSA) in the UK.
AB  - This review outlines the oral treatment options available for treating skin and
      soft-tissue infections due to methicillin-resistant Staphylococcus aureus (MRSA)
      in the community and discusses the evidence supporting their use.

PMID- 19101124
TI  - Comparison of biofilm-associated cell survival following in vitro exposure of
      meticillin-resistant Staphylococcus aureus biofilms to the antibiotics
      clindamycin, daptomycin, linezolid, tigecycline and vancomycin.
AB  - The efficacy of commonly used antistaphylococcal antimicrobials (clindamycin,
      linezolid and vancomycin) and recently developed antibiotics (daptomycin and
      tigecycline) was compared against clinical isolates of meticillin-resistant
      Staphylococcus aureus (MRSA). Minimum inhibitory concentrations (MICs), minimum
      bactericidal concentrations, time-kill kinetics and biofilm-associated cell
      survival were examined for 12 clinical isolates of MRSA treated with each
      antibiotic. The MIC ranges for daptomycin, linezolid, tigecycline, clindamycin
      and vancomycin were 0.06-0.25, 1-2, 0.06, 0.125-1024 and 0.5-1 microg/mL,
      respectively. Daptomycin and vancomycin were bactericidal following 6h of
      incubation with planktonic cells, whilst clindamycin, linezolid and tigecycline
      were bacteriostatic. None of the antibiotics killed 100% of biofilm-associated
      cells. Mean cell survival in biofilms treated with clindamycin, daptomycin,
      linezolid, tigecycline and vancomycin was 62%, 4%, 45%, 43% and 19%,
      respectively. Although all antibiotics were effective against planktonic
      staphylococcal populations, vancomycin and daptomycin possessed superior activity
      against biofilm-associated cells.

PMID- 19101125
TI  - Suicide attempts in bulimia nervosa: personality and psychopathological
      correlates.
AB  - BACKGROUND: Little evidence exists about suicidal acts in eating disorders and
      its relation with personality. We explored the prevalence of lifetime suicide
      attempts (SA) in women with bulimia nervosa (BN), and compared eating disorder
      symptoms, general psychopathology, impulsivity and personality between
      individuals who had and had not attempted suicide. We also determined the
      variables that better correlate with of SA. METHOD: Five hundred sixty-six BN
      outpatients (417 BN purging, 47 BN non-purging and 102 subthreshold BN)
      participated in the study. RESULTS: Lifetime prevalence of suicide attempts was
      26.9%. BN subtype was not associated with lifetime SA (p=0.36). Suicide
      attempters exhibited higher rates on eating symptomatology, general
      psychopathology, impulsive behaviors, more frequent history of childhood obesity
      and parental alcohol abuse (p<0.004). Suicide attempters exhibited higher scores
      on harm avoidance and lower on self-directedness, reward dependence and
      cooperativeness (p<0.002). The most strongly correlated variables with SA were:
      lower education, minimum BMI, previous eating disorder treatment, low self
      directedness, and familial history of alcohol abuse (p<0.006). CONCLUSION: Our
      results support the notion that internalizing personality traits combined with
      impulsivity may increase the probability of suicidal behaviors in these patients.
      Future research may increase our understanding of the role of suicidality to work
      towards rational prevention of suicidal attempts.

PMID- 19101127
TI  - Homonuclear dipolar decoupling schemes for fast MAS.
AB  - We present two one-dimensional methods that allow direct observation of highly
      resolved (1)H spectra in solid-state NMR. The methods, which work mainly at 30
      35kHz MAS speeds, are very robust and efficient. In addition, they present very
      few false resonances. The windowed smooth amplitude-modulated (wSAM) version has
      a potential to work at ultra-fast MAS provided the electronics is capable to
      define the pulse-shape in a smooth way, without any pulse transients.

PMID- 19101126
TI  - Reduced gray matter volume in ventral prefrontal cortex but not amygdala in
      bipolar disorder: significant effects of gender and trait anxiety.
AB  - Neuroimaging studies in bipolar disorder report gray matter volume (GMV)
      abnormalities in neural regions implicated in emotion regulation. This includes a
      reduction in ventral/orbital medial prefrontal cortex (OMPFC) GMV and,
      inconsistently, increases in amygdala GMV. We aimed to examine OMPFC and amygdala
      GMV in bipolar disorder type 1 patients (BPI) versus healthy control participants
      (HC), and the potential confounding effects of gender, clinical and illness
      history variables and psychotropic medication upon any group differences that
      were demonstrated in OMPFC and amygdala GMV. Images were acquired from 27 BPI (17
      euthymic, 10 depressed) and 28 age- and gender-matched HC in a 3T Siemens
      scanner. Data were analyzed with SPM5 using voxel-based morphometry (VBM) to
      assess main effects of diagnostic group and gender upon whole brain (WB) GMV.
      Post-hoc analyses were subsequently performed using SPSS to examine the extent to
      which clinical and illness history variables and psychotropic medication
      contributed to GMV abnormalities in BPI in a priori and non-a priori regions has
      demonstrated by the above VBM analyses. BPI showed reduced GMV in bilateral
      posteromedial rectal gyrus (PMRG), but no abnormalities in amygdala GMV. BPI also
      showed reduced GMV in two non-a priori regions: left parahippocampal gyrus and
      left putamen. For left PMRG GMV, there was a significant group by gender by trait
      anxiety interaction. GMV was significantly reduced in male low-trait anxiety BPI
      versus male low-trait anxiety HC, and in high- versus low-trait anxiety male BPI.
      Our results show that in BPI there were significant effects of gender and trait
      anxiety, with male BPI and those high in trait-anxiety showing reduced left PMRG
      GMV. PMRG is part of medial prefrontal network implicated in visceromotor and
      emotion regulation.

PMID- 19101128
TI  - Soft-particle model analysis of effect of LPS on electrophoretic softness of
      Acidithiobacillus ferrooxidans grown in presence of different metal ions.
AB  - The effect of surface lipopolysaccharides (LPS) on the electrophoretic softness
      and fixed charge density in the ion-penetrable layer of Acidithiobacillus
      ferrooxidans cells grown in presence of copper or arsenic ions have been
      discussed. The electrophoretic mobility data were analyzed using the soft
      particle electrophoresis theory. Cell surface potentials of all the strains based
      on soft-particle theory were lower than those estimated using the conventional
      Smoluchowski theory. Exposure to metal ions increased the surface electrophoretic
      softness with decrease in the fixed charge density. Effect of cell surface
      lipopolysaccharides on the model parameters are investigated and discussed.

PMID- 19101129
TI  - Noise-tolerant electrocardiogram beat classification based on higher order
      statistics of subband components.
AB  - OBJECTIVE: This paper presents a noise-tolerant electrocardiogram (ECG) beat
      classification method based on higher order statistics (HOS) of subband
      components. METHODS AND MATERIAL: Five levels of discrete wavelet transform (DWT)
      were applied to decompose the signal into six subband components. Higher order
      statistics proceeded to calculate four sets of HOS features from the three
      midband components, which together with three RR interval-related features
      constructed the primary feature set. A feature selection algorithm based on
      correlation coefficient and Fisher discriminality was then exploited to eliminate
      redundant features from the primary feature set. A feedforward backpropagation
      neural network (FFBNN) was employed as the classifier. Two sample selection
      strategies and four categories of noise artifacts were utilized to justify the
      capacity of the method. RESULTS: More than 97.5% discrimination rate was
      achieved, no matter which of the two sampling selection strategies was used. By
      using the feature selection method, the feature dimension can be readily reduced
      from 30 to 18 with negligible decrease in accuracy. Compared with other method in
      the literature, the proposed method improves the sensitivities of most beat
      types, resulting in an elevated average accuracy. The proposed method is tolerant
      to environmental noises; as high as 91% accuracies were retained even when
      contaminated with serious noises, 10 dB signal-to-noise ration (SNR), of
      different kinds. CONCLUSION: The results demonstrate the effectiveness and noise
      tolerant capacities of the proposed method in ECG beat classification.

PMID- 19101130
TI  - Clinical impact of computed tomography-based image-guided brachytherapy for
      cervix cancer using the tandem-ring applicator - the Addenbrooke's experience.
AB  - AIMS: We report our initial 3-year experience of chemoradiotherapy for cervical
      cancer with computed tomography-based image-guided high dose rate (HDR)
      brachytherapy using the tandem-ring applicator. MATERIALS AND METHODS: Twenty
      eight patients were treated between February 2005 and December 2007. All patients
      received initial external beam radiotherapy (EBRT) followed by HDR brachytherapy
      (planned dose 21 Gy to point A in three fractions over 8 days). For each
      insertion, a computed tomography scan was obtained with the brachytherapy
      applicator in situ. The cervix, uterus and organs at risk (OAR) were contoured on
      the computed tomography images to create an individualised dosimetry plan. The
      D(90) (the dose delivered to 90% of the tumour target), V(100) (the percentage of
      tumour target volume receiving 100% of the prescribed dose) and the minimum dose
      in the most exposed 2 cm(3) volume (D(2 cc)) of rectum, bladder and bowel were
      recorded. The equivalent dose in 2 Gy fractions delivered by EBRT and
      brachytherapy was calculated. RESULTS: The 3-year cancer-specific survival was
      81%, with a pelvic control rate of 96%. In 24 patients, a D(90)>or=74 Gy
      (alpha/beta10) was achieved. The only patient with local recurrence had a D(90)
      of 63.8 Gy(alpha/beta10). The overall actuarial risk of serious late morbidity
      was 14%. Seventeen patients had satisfactory OAR doses using the standard loading
      pattern. Seven patients had modifications to reduce the risk of toxicity, whereas
      two had modifications to improve the tumour dose. Comparison with a previous
      cohort of patients treated with chemoradiotherapy and a conventionally planned
      low dose rate triple source brachytherapy technique showed an improvement in
      local pelvic control of 20% (P=0.04). CONCLUSIONS: The implementation of a
      computed tomography-based tandem-ring HDR brachytherapy technique in conjunction
      with individual dose adaptation has resulted in a significant improvement in
      local control at Addenbrooke's without increasing the risk of serious toxicity,
      and with little effect on radiotherapy resources.

PMID- 19101131
TI  - Theorizing "Big Events" as a potential risk environment for drug use, drug
      related harm and HIV epidemic outbreaks.
AB  - Political-economic transitions in the Soviet Union, Indonesia, and China, but not
      the Philippines, were followed by HIV epidemics among drug users. Wars also may
      sometimes increase HIV risk. Based on similarities in some of the causal pathways
      through which wars and transitions can affect HIV risk, we use the term "Big
      Events" to include both. We first critique several prior epidemiological models
      of Big Events as inadequately incorporating social agency and as somewhat
      imprecise and over-generalizing in their sociology. We then suggest a model using
      the following concepts: first, event-specific HIV transmission probabilities are
      functions of (a) the probability that partners are infection-discordant; (b) the
      infection-susceptibility of the uninfected partner; (c) the infectivity of the
      infected--as well as (d) the behaviours engaged in. These probabilities depend on
      the distributions of HIV and other variables in populations. Sexual or injection
      events incorporate risk behaviours and are embedded in sexual and injection
      partnership patterns and community networks, which in turn are shaped by the
      content of normative regulation in communities. Wars and transitions can change
      socio-economic variables that can sometimes precipitate increases in the numbers
      of people who engage in high-risk drug and sexual networks and behaviours and in
      the riskiness of what they do. These variables that Big Events affect may include
      population displacement; economic difficulties and policies; police corruption,
      repressiveness, and failure to preserve order; health services; migration; social
      movements; gender roles; and inter-communal violence--which, in turn, affect
      normative regulation, youth alienation, networks and behaviours. As part of these
      pathways, autonomous action by neighbourhood residents, teenagers, drug users and
      sex workers to maintain their economic welfare, health or happiness may affect
      many of these variables or otherwise mediate whether HIV epidemics follow
      transitions. We thus posit that research on whether and how these interacting
      causal pathways and autonomous actions are followed by drug-related harm and/or
      HIV or other epidemics can help us understand how to intervene to prevent or
      mitigate such harms.

PMID- 19101132
TI  - Foucault on methadone: beyond biopower.
AB  - This essay reviews four texts which critically analyse methadone maintenance
      therapy using Foucault as a key theoretical framework: [Friedman, J., & Alicea,
      M. (2001). Surviving heroin: Interviews with women in methadone clinics. Florida:
      University Press of Florida], [Bourgois, P. (2000). Disciplining addictions: The
      bio-politics of methadone and heroin in the United States. Culture Medicine and
      Psychiatry, 24, 165-195], [Bull, M. (2008). Governing the heroin trade: From
      treaties to treatment. Ashgate: Aldershot], and [Fraser, S., & valentine, k.
      (2008). Substance & substitution: Methadone subjects in liberal societies. New
      York: Palgrave Macmillan]. Taken together these works demonstrate one trajectory
      in the development of critical drug studies over the past decade. While all four
      view MMT as a regulatory technology which aims to create productive and obedient
      subjects, their understandings of the power relations of the clinic are quite
      distinct. The first two texts emphasise the social control of drug users, the
      third, issues of governmentality and liberal political practice, while the fourth
      engages with ontological questions about substances themselves. Thus while
      Foucauldian analysis has become familiar in social studies of drugs and alcohol,
      new uses for its conceptual tools continue to emerge.

PMID- 19101133
TI  - Processing of poultry feathers by alkaline keratin hydrolyzing enzyme from
      Serratia sp. HPC 1383.
AB  - The present study describes the production and characterization of a feather
      hydrolyzing enzyme by Serratia sp. HPC 1383 isolated from tannery sludge, which
      was identified by the ability to form clear zones around colonies on milk agar
      plates. The proteolytic activity was expressed in terms of the micromoles of
      tyrosine released from substrate casein per ml per min (U/mL min). Induction of
      the inoculum with protein was essential to stimulate higher activity of the
      enzyme, with 0.03% feathermeal in the inoculum resulting in increased enzyme
      activity (45U/mL) that further increased to 90U/mL when 3d old inoculum was used.
      The highest enzyme activity, 130U/mL, was observed in the presence of 0.2% yeast
      extract. The optimum assay temperature and pH for the enzyme were found to be 60
      degrees C and 10.0, respectively. The enzyme had a half-life of 10min at 60
      degrees C, which improved slightly to 18min in presence of 1mM Ca(2+). Inhibition
      of the enzyme by phenylmethyl sulfonyl fluoride (PMSF) indicated that the enzyme
      was a serine protease. The enzyme was also partially inhibited (39%) by the
      reducing agent beta-mercaptoethanol and by divalent metal ions such as Zn(2+)
      (41% inhibition). However, Ca(2+) and Fe(2+) resulted in increases in enzyme
      activity of 15% and 26%, respectively. The kinetic constants of the keratinase
      were found to be 3.84 microM (K(m)) and 108.7 microM/mLmin (V(max)). These
      results suggest that this extracellular keratinase may be a useful alternative
      and eco-friendly route for handling the abundant amount of waste feathers or for
      applications in other industrial processes.

PMID- 19101134
TI  - Design rule for optimization of microelectrodes used in electric cell-substrate
      impedance sensing (ECIS).
AB  - This paper presents an experimentally derived design rule for optimization of
      microelectrodes used in electric cell-substrate impedance sensing (ECIS) up to
      10MHz. The effect of change in electrode design (through electrode sensor area,
      lead trace widths, and passivation coating thickness) on electrode
      characteristics was experimentally evaluated using electrochemical impedance
      spectroscopy (EIS) measurements and analyzed using equivalent circuit models. A
      parasitic passivation coating impedance was successfully minimized by designing
      electrodes with either a thicker passivation layer or a smaller lead trace area.
      It was observed that the passivated lead trace area to passivation coating
      thickness ratio has a critical value of 5.5, under which the impedance
      contribution of the coating is minimized. The optimized design of ECIS-based
      microelectrode devices reported in this work will make it possible to probe the
      entire beta dispersion region of adherent biological cell layers by reducing
      measurement artifacts and improving the quality of data across the beta
      dispersion region. The new design will enable the use of the commonly used ECIS
      technique to measure real-time cellular properties in high frequency ranges (beta
      dispersion) that was not possible thus far.

PMID- 19101135
TI  - Au nanoparticles grafted sandwich platform used amplified small molecule
      electrochemical aptasensor.
AB  - We report a sensitively amplified electrochemical aptasensor using adenosine
      triphosphate (ATP) as a model. ATP is a multifunctional nucleotide that is most
      important as a "molecular currency" of intracellular energy transfer. In the
      sensing process, duplexes consisting of partly complementary strand (PCS1), ATP
      aptamer (ABA) and another partly complementary strand (PCS2) were immobilized
      onto Au electrode through the 5'-HS on the PCS1. Meanwhile, PCS2 was grafted with
      the Au nanoparticles (AuNPs) to amplify the detection signals. In the absence of
      ATP, probe methylene blue (MB) bound to the DNA duplexes and also bound to
      guanine bases specifically to produce a strong differential pulse voltammetry
      (DPV) signal. But when ATP exists, the ABA-PCS2 or ABA-PCS1 part duplexes might
      be destroyed, which decreased the amount of MB on the electrode and led to
      obviously decreased DPV signal. This phenomenon can be used to detect ATP and get
      a very sensitive detection limit low to 0.1nM, and the detection range could
      extend up to 10(-7)M. Compared to the sensing platform without PCS2 grafted
      AuNPs, amplified function of this sensing system was also evidently proved.
      Therefore, such PCS1-ABA-PCS2/AuNPs sensing system could provide a promising
      signal-amplified model for aptamer-based small-molecules detection.

PMID- 19101136
TI  - In vitro study on the individual and synergistic cytotoxicity of adriamycin and
      selenium nanoparticles against Bel7402 cells with a quartz crystal microbalance.
AB  - Selenium nanoparticles (Se NPs) were prepared based on the reduction of selenious
      acid (H(2)SeO(3)), by employing sodium alginate (SA) as a template. The real-time
      monitoring of the drug-inducing apoptosis process of human hepatic cancer cells
      Bel7402 was performed with the quartz crystal microbalance (QCM) measurement. The
      anti-tumor effect of adriamycin (ADM) used in combination with Se NPs was
      investigated. It is found that both drugs were able to inhibit cell proliferation
      in a dose-dependent way and the combined treatment with ADM and Se NPs was more
      effective in inhibiting cell growth than each of the two drugs alone. The
      cytotoxic effects of drug combination were evaluated with the modified Burgi
      formula (Jin equation) based the Deltaf(0) responses. The grades gradually
      changed from apparent synergism to simple addition with the drug-treatment time
      increasing but the drug combination with lower concentrations still exhibited
      synergism after 24h, suggesting a potential application in cancer therapy.

PMID- 19101137
TI  - Combination of sorafenib and doxorubicin in patients with advanced hepatocellular
      carcinoma: results from a phase I extension trial.
AB  - Sorafenib, an oral multikinase inhibitor, shows efficacy in renal cell and
      hepatocellular carcinoma (HCC) and is well tolerated when combined with
      doxorubicin in other solid tumours. Eighteen patients with inoperable HCC
      received doxorubicin 60 mg/m(2) IV for up to six 3-week cycles. Sorafenib 400mg
      bid was administered continuously starting day 4. Patients discontinuing
      doxorubicin were eligible for sorafenib monotherapy. The most frequent grade 3-4
      drug-related adverse events were neutropaenia (61%), leukopaenia (45%) and
      diarrhoea (17%, grade 3). Seven of eight patients who completed six cycles of
      doxorubicin continued treatment with sorafenib for at least 3 months. Doxorubicin
      moderately increased AUC (21%) and C(max) (33%) when administered with sorafenib.
      The disease control rate for 16 evaluable patients was 69%. Sorafenib plus
      doxorubicin appears to be well tolerated and more effective in the treatment of
      HCC than doxorubicin alone. Follow-up with single-agent sorafenib in these
      patients also appears to be well tolerated.

PMID- 19101138
TI  - Lessons learned from independent central review.
AB  - Independent central review (ICR) is advocated by regulatory authorities as a
      means of independent verification of clinical trial end-points dependent on
      medical imaging, when the data from the trials may be submitted for licensing
      applications [Food and Drug Administration. United States food and drug
      administration guidance for industry: clinical trial endpoints for the approval
      of cancer drugs and biologics. Rockville, MD: US Department of Health and Human
      Services; 2007; Committee for Medicinal Products for Human Use. European
      Medicines Agency Committee for Medicinal Products for Human Use (CHMP) guideline
      on the evaluation of anticancer medicinal products in man. London, UK: European
      Medicines Agency; 2006; United States Food and Drug Administration Center for
      Drug Evaluation and Research. Approval package for application number NDA 21-492
      (oxaliplatin). Rockville, MD: US Department of Health and Human Services; 2002;
      United States Food and Drug Administration Center for Drug Evaluation and
      Research. Approval package for application number NDA 21-923 (sorafenib
      tosylate). Rockville, MD: US Department of Health and Human Services; 2005;
      United States Food and Drug Administration Center for Drug Evaluation and
      Research. Approval package for application number NDA 22-065 (ixabepilone).
      Rockville, MD: US Department of Health and Human Services; 2007; United States
      Food and Drug Administration Center for Drug Evaluation and Research. Approval
      package for application number NDA 22-059 (lapatinib ditosylate). Rockville, MD:
      US Department of Health and Human Services; 2007; United States Food and Drug
      Administration Center for Biologics Evaluation and Research. Approval package for
      BLA numbers 97-0260 and BLA Number 97-0244 (rituximab). Rockville, MD: US
      Department of Health and Human Services; 1997; United States Food and Drug
      Administration. FDA clinical review of BLA 98-0369 (Herceptin((R)) trastuzumab
      (rhuMAb HER2)). FDA Center for Biologics Evaluation and Research; 1998; United
      States Food and Drug Administration. FDA Briefing Document Oncology Drugs
      Advisory Committee meeting NDA 21801 (satraplatin). Rockville, MD: US Department
      of Health and Human Services; 2007; Thomas ES, Gomez HL, Li RK, et al.
      Ixabepilone plus capecitabine for metastatic breast cancer progressing after
      anthracycline and taxane treatment. JCO 2007(November):5210-7]. In addition,
      clinical trial sponsors have used ICR in Phase I-II studies to assist in critical
      pathway decisions including in-licensing of compounds [Cannistra SA, Matulonis
      UA, Penson RT, et al. Phase II study of bevacizumab in patients with platinum
      resistant ovarian cancer or peritoneal serous cancer. JCO 2007(November):5180-6;
      Perez EA, Lerzo G, Pivot X, et al. Efficacy and safety of ixabepilone (BMS
      247550) in a phase II study of patients with advanced breast cancer resistant to
      an anthracycline, a taxane, and capecitabine. JCO 2007(August):3407-14; Vermorken
      JB, Trigo J, Hitt R, et al. Open-label, uncontrolled, multicenter phase II study
      to evaluate the efficacy and toxicity of cetuximab as a single agent in patients
      with recurrent and/or metastatic squamous cell carcinoma of the head and neck who
      failed to respond to platinum-based therapy. JCO 2007(June):2171-7; Ghassan KA,
      Schwartz L, Ricci S, et al. Phase II study of sorafenib in patients with advanced
      hepatocellular carcinoma. JCO 2006(September):4293-300; Boue F, Gabarre J,
      GaBarre J, et al. Phase II trial of CHOP plus rituximab in patients with HIV
      associated non-Hodgkin's lymphoma. JCO 2006(September):4123-8; Chen HX, Mooney M,
      Boron M, et al. Phase II multicenter trial of bevacizumab plus fluorouracil and
      leucovorin in patients with advanced refractory colorectal cancer: an NCI
      Treatment Referral Center Trial TRC-0301. JCO 2006(July):3354-60; Ratain MJ,
      Eisen T, Stadler WM, et al. Phase II placebo-controlled randomized
      discontinuation trial of sorafenib in patients with metastatic renal cell
      carcinoma. JCO 2006(June):2502-12; Jaffer AA, Lee FC, Singh DA, et al.
      Multicenter phase II trial of S-1 plus cisplatin in patients with untreated
      advanced gastric or gastroesophageal junction adenocarcinoma. JCO
      2006(February):663-7; Bouche O, Raoul JL, Bonnetain F, et al. Randomized
      multicenter phase II trial of a biweekly regimen of fluorouracil and leucovorin
      (LV5FU2), LV5FU2 plus cisplatin, or LV5FU2 plus irinotecan in patients with
      previously untreated metastatic gastric cancer: a Federation Francophone de
      Cancerologie Digestive Group Study-FFCD 9803. JCO 2004(November):4319-28]. This
      article will focus on the definition and purpose of ICR and the issues and
      lessons learned in the ICR setting primarily in Phase II and III oncology
      studies. This will include a discussion on discordance between local and central
      interpretations, consequences of ICR, reader discordance during the ICR,
      operational considerations and the need for specific imaging requirements as part
      of the study protocol.

PMID- 19101140
TI  - Effectiveness of immediate preoperative injection of radiopharmaceutical and blue
      dye for sentinel node biopsy in patients with breast cancer.
AB  - BACKGROUND: Sentinel node biopsy (SNB) in breast cancer conventionally utilises a
      preoperative radioisotope injection and lymphoscintigraphy, which is time
      consuming and painful. The aim of this study was to evaluate a potentially more
      efficient and practical technique of immediate preoperative injection of blue dye
      and radiopharmaceutical by the surgeon (without involvement of a nuclear medicine
      department). METHOD: One hundred and sixty three clinically node negative
      patients with invasive breast cancer undergoing breast-conserving surgery were
      included. The radiopharmaceutical was delivered to the operating suite and
      injected by the surgeon in the subareolar region immediately after induction of
      anaesthesia. Sentinel node biopsy was performed in conjunction with removal of
      any palpable axillary lymph nodes (axillary node sampling). RESULTS: Sentinel
      nodes (SNs) were detected in 161 of 163 women. On average, 3.0 sentinel nodes
      were identified. Twenty nine patients had involved nodes of whom 28 had a
      positive sentinel node. Of the two patients with failed identification, one had
      involved axillary lymph nodes on sampling and the other had an involved
      intramammary lymph node. CONCLUSION: This method produces results identical to
      those obtained with other techniques. This study shows that sentinel node biopsy
      can be performed safely without involvement of a nuclear medicine department with
      the added benefits of no preoperative injection and improved efficiency in the
      operating suite.

PMID- 19101141
TI  - Training on N.O.T.E.S.: from history we learn.
AB  - Surgical errors occurring early in the learning curve of laparoscopic surgery
      providers delayed the uptake and progress of minimally invasive surgery (MIS) for
      years. This taught us a valuable lesson; innovations in surgical techniques
      should not be rapidly implemented until all aspects including applicability,
      feasibility and safety have been fully tested. In 2005, the Natural Orifice
      Surgery Consortium for Assessment and Research (NOSCAR) published a white paper
      highlighting the barriers to NOTES development and identifying key elements for
      its progress. One of these elements is the training of future providers.
      Proficiency-based, virtual reality simulation will offer a feasible alternative
      to animal testing once the safety and efficacy parameters of NOTES are
      established. Recent advances in imaging including computed tomography (CT)
      scanning, magnetic resonance imaging (MRI) scanning, and ultrasound (US) scanning
      can offer improved image registration and real-time tracking. Combining these
      advanced imaging technologies with the newly designed virtual reality simulators
      will result in a fully comprehensive simulation curriculum which will offer a
      unique facility for future NOTES providers to train anytime, anywhere, and as
      much as they need to in order to achieve the pre-set proficiency levels for a
      variety of NOTES procedures. Furthermore they will incorporate patient-specific
      anatomical models obtained from patient imaging and uploaded onto the simulator
      to ensure face reliability and validity assurance. Training in a clean, safe
      environment with proximate feedback and performance analysis will help accelerate
      the learning curve and therefore improve patients' safety and outcomes in order
      to maximize the benefits of innovative access procedures such as NOTES.

PMID- 19101139
TI  - Functional role of the KLF6 tumour suppressor gene in gastric cancer.
AB  - Gastric cancer is the second most common cancer and a leading cause of cancer
      related death worldwide. The Kruppel-like factor 6 (KLF6) tumour suppressor gene
      had been previously shown to be inactivated in a number of human cancers through
      loss of heterozygosity (LOH), somatic mutation, decreased expression and
      increased alternative splicing into a dominant negative oncogenic splice variant,
      KLF6-SV1. In the present study, 37 gastric cancer samples were analysed for the
      presence of loss of heterozygosity (LOH) of the KLF6 locus and somatic mutation.
      In total, 18 of 34 (53%) of the gastric cancer samples analysed demonstrated KLF6
      locus specific loss. Four missense mutations, such as T179I, R198G, R71Q and
      S180L, were detected. Interestingly, two of these mutations R71Q and S180L have
      been identified independently by several groups in various malignancies including
      prostate, colorectal and gastric cancers. In addition, decreased wild-type KLF6
      (wtKLF6) expression was associated with loss of the KLF6 locus and was present in
      48% of primary gastric tumour samples analysed. Functional studies confirmed that
      wtKLF6 suppressed proliferation of gastric cancer cells via transcriptional
      regulation of the cyclin-dependent kinase inhibitor p21 and the oncogene c-myc.
      Functional characterisation of the common tumour-derived mutants demonstrated
      that the mutant proteins fail to suppress proliferation and function as dominant
      negative regulators of wtKLF6 function. Furthermore, stable overexpression of the
      R71Q and S180L tumour-derived mutants in the gastric cancer cell line, Hs746T,
      resulted in an increased tumourigenicity in vivo. Combined, these findings
      suggest an important role for the KLF6 tumour suppressor gene in gastric cancer
      development and progression and identify several highly cancer-relevant
      signalling pathways regulated by the KLF6 tumour suppressor gene.

PMID- 19101142
TI  - Microbial production of poly-beta-hydroxybutyrate by marine microbes isolated
      from various marine environments.
AB  - Considering the industrial interest of Poly-beta-hydroxybutyrate (PHB), bacteria
      isolated from the various marine arenas were screened for their ability to
      accumulate PHB and were compared with Wausteria eutropha (MTCC-1285). Among the
      42 isolates, four strains showed the accumulation of PHB. The maximum PHB
      producer Vibrio sp. (MK4) was further studied in detail. To increase the
      productivity, steps were taken to evaluate the effect of carbon sources, nitrogen
      sources, pH and sodium chloride concentration on PHB productivity by MK4. The
      optimized conditions were further used for the batch fermentation over a period
      of 72 h. Significantly higher maximum biomass of 9.1g/L with a PHB content of
      4.223 g/L was obtained in a laboratory-scale bioreactor at 64 h, thus giving a
      productivity of 0.065 g/L/h. The extracted polymer was compared with the
      authentic PHB and was confirmed to be PHB using FTIR analysis and (1)H NMR
      analysis. Thus, the study highlights the potential of the use of Vibrio sp (MK4)
      in the commercial production of PHB.

PMID- 19101144
TI  - New analogues of agmatine with higher affinity to imidazoline receptors.
AB  - Compilation of agmatine structure and imidazoline ring leads to a new family of
      imidazoline/alpha(2)-adrenoceptor ligands, 4(5)-(2-aminoethyl)imidazoline
      derivatives. Constraining of the guanidine moiety into heterocyclic ring improved
      the affinities of the resultant fusion compounds in comparison to agmatine
      itself. In this work, the synthetic approach and results for I(1), I(2), and
      alpha(2)-adrenoceptors affinities are reported.

PMID- 19101145
TI  - Spinal tumors in neurofibromatosis-2: management considerations - a review.
AB  - Neurofibromatosis Type 2 (NF-2) is a distinct clinical entity, characterized by
      multiple intracranial and spinal tumors. While bilateral vestibular schwannomas
      are the pathological hallmark of the disease, significant morbidity in NF-2 is
      attributable to the presence of both intramedullary and extramedullary spinal
      tumors. With the advent of MRI as a screening modality, multiple, extensive
      spinal tumors in the NF-2 population are often seen, which may be clinically
      quiescent at the time of initial diagnosis. All NF-2 patients should have routine
      screening with full spinal MRI at the time of diagnosis, regardless of symptoms.
      Early surgical intervention is indicated in cases where a neurological deficit is
      attributable to a focal expanding spinal lesion. In asymptomatic patients, the
      decision to operate is tailored to the individual patient, with the ultimate goal
      of preserving function. In these cases, surgery should be considered where there
      is evidence of progressive tumor growth, with attendant risk to the patient of
      functional deterioration.

PMID- 19101143
TI  - Discovery and optimization of imidazo[1,2-a]pyridine inhibitors of insulin-like
      growth factor-1 receptor (IGF-1R).
AB  - The optimization of imidazo[1,2-a]pyridine inhibitors as potent and selective
      inhibitors of IGF-1R is presented. Further optimization of oral exposure in mice
      is also discussed. Detailed selectivity, in vitro activity, and in vivo PK
      profiles of an optimized compound is also highlighted.

PMID- 19101146
TI  - Impact of bilateral anterior cingulotomy on neurocognitive function in patients
      with intractable pain.
AB  - Although the cingulate cortices are important with regard to neurocognitive
      functions, outcome studies usually fail to identify evident cognitive dysfunction
      following anterior cingulotomy. The aim of this study was to document any
      impairment of neurocognitive functions following anterior cingulotomy. Between
      September 2002 and April 2004, 10 patients underwent stereotactic bilateral
      anterior cingulotomy for intractable cancer pain. A neuropsychological assessment
      of each patient was performed 1 day prior to surgery and 1 week and 1 month post
      operatively. Assessment of pain relief was evaluated with a short form of the
      McGill pain questionnaire. Six of the 10 patients achieved fair to good pain
      relief following the cingulotomy procedure. Most neurocognitive functions,
      including language, memory, motor, visual-constructional, and intellectual
      functions, remained unaffected. A decline in focused attention performance was
      identified at the early post-operative assessment. The results of this
      longitudinal evaluation will help to better define the risk-to-benefit profile of
      cingulotomy for intractable pain.

PMID- 19101147
TI  - Visualizing cells at the nanoscale.
AB  - Cryogenic electron tomography (cryo- ET) enables the 3D visualization of
      biological material at a previously unseeable scale. Carefully controlled
      cryogenic specimen preparation avoids the artefacts that are notorious to
      conventional electron microscopy specimen preparation. To date, studies employing
      cryo- ET have mostly been restricted to isolated macromolecular assemblies, small
      prokaryotic cells or thin regions of eukaryotic cells owing to the limited
      penetration depth of electrons through ice-embedded preparations. Recent progress
      in cryosectioning makes it possible to acquire tomograms from many kinds of
      vitrified cells and tissues. The systematic and comprehensive interpretation of
      such tomograms will provide unprecedented insight into the molecular organization
      of cellular landscapes.

PMID- 19101148
TI  - In vivo kinematic determination of total knee arthroplasty from squatting to
      standing.
AB  - This study analyzed three dimensional (3D) in vivo kinematic data from the
      squatting to standing position for 18 Japanese subjects (18 knees) implanted with
      either Legacy((R)) Posterior Stabilized (LPS) Flex Fixed Bearing TKA or LPS Flex
      Mobile Bearing TKA. Under weight-bearing conditions, for all patients, the
      average roll-forward motions for the medial and lateral condyles were 4.0+/-3.6
      mm and 6.3+/-3.4 mm, and the average external axial rotation was 3.1 degrees +/
      4.1 degrees . For both groups, the weight-bearing range-of-motion (ROM) (110.7
      degrees +/-12.7 degrees ) was less than pre (127.2+/-15.5 degrees ) and post
      (135.6+/-5.4 degrees ) operative non-weight bearing ROM. As hypothesized, the
      incidence, average and maximum lift off for the squatting to standing activity
      were much less than those of deep knee bend (DKB), and condylar motions and
      kinematics were opposite that of the DKB. There was little statistical difference
      of their kinematic patterns during this activity between the LPS fixed and mobile
      TKA implants.

PMID- 19101149
TI  - Histological evaluation of spontaneous osteonecrosis of the medial femoral
      condyle and short-term clinical results of osteochondral autografting: a case
      series.
AB  - Although many surgical modalities for spontaneous osteonecrosis of the knee
      (SONK) of the medial femoral condyle have been reported, few reports have
      described these treatment options from the etiological point of view. Recently,
      osteochondral autografting has gained popularity for use in small cartilage
      injuries. The aims of this study were to characterize the SONK lesion
      histopathologically and to report on preliminary clinical results of autogenous
      osteochondral grafting for SONK. Six patients with SONK of the medial femoral
      condyle underwent osteochondral autografting. Average age was 54.2 years (range,
      50-57 years). Using Koshino's classification, three patients' lesions were
      classified as stage III and three as stage IV. Classical histological
      investigation of the lesions was performed in all cases. All the patients
      achieved favorable pain relief after osteochondral autografts. The mean duration
      of follow-up was 27.7 months (range, 23-45 months). An increase in the average
      Lysholm score was found, ranging from 54.7 preoperatively to 92.3
      postoperatively. Histological investigation of the lesions revealed articular
      bone plate fracture with enchondral ossification, reactive cartilage tissue
      formation, and proliferation of fibrous tissue. An area of osteonecrosis was
      observed in detached or fragmented osteochondral lesions. Osteochondral
      autografting was performed on six patients for the SONK and the short-term
      clinical results were favorable. Histological results give support to subchondral
      fracture as the etiological mechanism underlying SONK.

PMID- 19101150
TI  - Placement of a palpable marker adjacent to the mid-inguinal point: assessment of
      a clinical method for detecting the femoral head centre during knee arthroplasty.
AB  - Localization of the centre of the femoral head is vital when using extra
      medullary femoral alignment systems in knee arthroplasty. This study investigated
      the accuracy of a palpable marker placed in the groin for detecting the centre of
      the femoral head. A table tennis ball, 38 mm in diameter, was taped 2.5 cm
      perpendicular to the mid-inguinal point in patients having a plain radiograph of
      the pelvis. The mean horizontal distance between the centre of the table tennis
      ball and a vertical line passing through the centre of the femoral head was 8.62
      mm (range 0-28.6, SD 6.76). In 100% of cases the horizontal distance between the
      centre of the table tennis ball and a vertical line passing through the centre of
      the femoral head was less than one diameter of the table tennis ball. Using a
      theoretical mechanical axis model our clinical method would confer an error equal
      to or less than 2 degrees from the weight-bearing axis of the knee in up to 98%
      of cases. In conclusion, our results suggest that the clinical method reported
      here provides a simple and reliable way of localizing the centre of the femoral
      head in knee arthroplasty.

PMID- 19101151
TI  - Synthesis and evaluation of Hsp90 inhibitors that contain the 1,4-naphthoquinone
      scaffold.
AB  - High-throughput screening of a library of diverse molecules has identified the
      1,4-naphthoquinone scaffold as a new class of Hsp90 inhibitors. The synthesis and
      evaluation of a rationally-designed series of analogues containing the
      naphthoquinone core scaffold has provided key structure-activity relationships
      for these compounds. The most active inhibitors exhibited potent in vitro
      activity with low micromolar IC(50) values in anti-proliferation and Her2
      degradation assays. In addition, 3g, 12, and 13a induced the degradation of
      oncogenic Hsp90 client proteins, a hallmark of Hsp90 inhibition. The
      identification of these naphthoquinones as Hsp90 inhibitors provides a new
      scaffold upon which improved Hsp90 inhibitors can be developed.

PMID- 19101152
TI  - A novel side-bridged hybrid phosphonate/acetate pendant cyclam: synthesis,
      characterization, and 64Cu small animal PET imaging.
AB  - Copper-64 (t(1/2)=12.7h; beta(+): 0.653 MeV, 17.4%; beta(-): 0.578 MeV, 39%) is
      produced in a biomedical cyclotron and has applications in both imaging and
      therapy. Macrocyclic chelators are widely used as bifunctional chelators to bind
      copper radionuclides to antibodies and peptides owing to their relatively high
      kinetic stability. A novel side-bridged cyclam featuring both pendant acetate and
      phosphonate groups was synthesized using a Kabachnik-Fields approach followed by
      hydrobromic acid deprotection. The Cu(II) complex of the novel ligand was
      synthesized, radiolabeling with (64)Cu was demonstrated, and in vitro (serum)
      stability was performed. In addition, in vivo distribution and clearance of the
      (64)Cu-labeled complex was visualized by positron emission tomography (PET)
      imaging. This novel chelate may be useful in (64)Cu-mediated diagnostic positron
      emission tomography (PET) imaging as well as targeted radiotherapeutic
      applications.

PMID- 19101153
TI  - Discovery and structure-activity relationships of a novel series of benzopyran
      based K(ATP) openers for urge urinary incontinence.
AB  - A novel series of benzopyran derivatives were synthesized and evaluated as K(ATP)
      channel openers. Structure-activity relationships were investigated around 4
      position of the benzopyran nucleus. Optimization of 4-substituent with some
      heterocyclic rings led to compound 13b bearing a benzo[d]isoxazol-3-one moiety as
      a potent and selective K(ATP) channel opener in vitro. In two anesthetized rat
      models of myogenic bladder overactivity, compound 13b was found to inhibit
      spontaneous bladder contractions.

PMID- 19101154
TI  - Synthesis of isothiazol-3-one derivatives as inhibitors of histone
      acetyltransferases (HATs).
AB  - High-throughput screening led to the identification of isothiazolones 1 and 2 as
      inhibitors of histone acetyltransferase (HAT) with IC50s of 3 microM and 5
      microM, respectively. Analogues of these hit compounds with variations of the N
      phenyl group, and with variety of substituents at C-4, C-5 of the thiazolone
      ring, were prepared and assayed for inhibition of the HAT enzyme PCAF. Potency is
      modestly favoured when the N-aryl group is electron deficient (4-pyridyl
      derivative 10 has IC(50)=1.5 microM); alkyl substitution at C-4 has little
      effect, whilst similar substitution at C-5 causes a significant drop in potency.
      The ring-fused compound 38 has activity (IC(50)=6.1 microM) to encourage further
      exploration of this bicyclic structure. The foregoing SAR is consistent with an
      inhibitory mechanism involving cleavage of the S-N bond of the isothiazolone ring
      by a catalytically important thiol residue.

PMID- 19101155
TI  - Arylphthalazines as potent, and orally bioavailable inhibitors of VEGFR-2.
AB  - A series of arylphthalazine derivatives were synthesized and evaluated as
      antagonists of VEGF receptor II (VEGFR-2). IM-094482 57, which was prepared in
      two steps from commercially available starting materials, was found to be a
      potent inhibitor of VEGFR-2 in enzymatic, cellular and mitogenic assays
      (comparable activity to ZD-6474). Additionally, 57 inhibited the related
      receptor, VEGF receptor I (VEGFR-1), and showed excellent exposure when dosed
      orally to female CD-1 mice.

PMID- 19101156
TI  - Discovery of 13-oxa prostaglandin analogs as antiglaucoma agents: synthesis and
      biological activity.
AB  - FP-Class prostaglandin analogs have demonstrated utility for the treatment of
      glaucoma and ocular hypertension. A series of novel FP prostaglandin analogs was
      designed to optimize topical ocular activity and reduce ocular side-effects by
      replacing 13-carbon with oxygen. A facile synthesis was successfully developed
      for synthesis of the 13-oxa prostaglandins from the commercially available Corey
      aldehyde benzoate. Among the compounds synthesized, AL-16082 was the most potent
      prostaglandin FP agonist in vitro. In a prostaglandin FP receptor-linked second
      messenger assay, phosphoinositide (PI) turnover, it exhibited a potency value
      (EC(50)) of 1.9 nM (78% max. response relative to fluprostenol). The isopropyl
      ester of AL-16082, compound AL-16049, significantly lowered intraocular pressure
      (IOP) in the ocular hypertensive monkey eyes by 30%. In the study of acute ocular
      irritation response in New Zealand albino rabbits, AL-16049 produced lower
      incidence of hyperemia, swelling, and discharge than PGF(2alpha) (1 microg), and
      a similar incidence of hyperemia, swelling, and discharge to latanoprost (1.8
      microg). AL-16049 also produced no signs of ocular irritation or discomfort in
      the cat at the doses evaluated.

PMID- 19101157
TI  - Pestalofones A-E, bioactive cyclohexanone derivatives from the plant endophytic
      fungus Pestalotiopsis fici.
AB  - Pestalofones A-E (1-5), five new cyclohexanone derivatives, have been isolated
      from cultures of the plant endophytic fungus Pestalotiopsis fici, along with the
      known compounds, isosulochrin (6), isosulochrin dehydrate (7), and iso-A82775C
      (8). The structures of 1-5 were determined by NMR spectroscopy, and the absolute
      configuration of 1 was assigned using the modified Mosher method. Compounds 1, 2,
      and 5 displayed inhibitory effects on HIV-1 replication in C8166 cells, whereas 3
      and 5 showed significant antifungal activity against Aspergillus fumigatus.

PMID- 19101158
TI  - Synthesis and antitumor activity of novel amsacrine analogs: the critical role of
      the acridine moiety in determining their biological activity.
AB  - A new series of N-[4-(2'-oxo-2H-pyrano[2,3-b]quinolin-5'-ylamino)-phenyl]
      methanesulfonamides was prepared and analyzed as novel amsacrine-like
      derivatives. Our preliminary biological evaluation has shown that the replacement
      of the acridine moiety with the analogous 2-oxo-2H-pyrano[2,3-b]quinoline system
      drastically reduced both their anticancer activity and their propency to
      intercalate into double stranded DNA.

PMID- 19101160
TI  - Micromorphology of epicuticular wax structures of the garden strawberry leaves by
      electron microscopy: syntopism and polymorphism.
AB  - Ultrastructural aspects of leaf epicuticular wax structures were investigated in
      the garden strawberry Fragariaxananassa by scanning and transmission electron
      microscopy. Both the adaxial and abaxial surfaces of two cultivars (Maehyang and
      Red Pearl) were collected and subjected to surface observations and ultrathin
      sections. The most prominent leaf epicuticular wax structures included
      membraneous platelets and angular rodlets. Most wax platelets were membraneous,
      and appeared to protrude from the surface at an acute angle. Angular rodlets were
      usually bent and had rather distinct facets in the abaxial surface of the two
      cultivars. Membraneous platelets were predominant on the adaxial surface of
      Maehyang, whereas the adaxial surface of Red Pearl was characterized by angular
      rodlets. However, both cultivars possessed angular rodlets on the abaxial
      surface, simultaneously. The combination of air-drying without vacuum and in-lens
      imaging of secondary electron signals with a field emission gun could impart the
      superb resolution at low electron dose with minimal specimen shrinkage. In
      vertical profiles of the leaf epidermis, epicuticular waxes were observed above
      the cuticle layer, and measured approximately as 50nm in thickness. The natural
      epicuticular waxes were seemingly mixtures of electron-dense microfibrils, and
      heterogeneous in shape on ultrathin sections. Distinct crystal-like strata could
      be hardly discernable in the wax structures. These results suggest that the
      garden strawberry has the nature of syntopism within one plant and polymorphism
      within the same species in the formation and occurrence of leaf epicuticular
      waxes.

PMID- 19101159
TI  - Scanning electron microscopy studies of antennal sensilla of bruchid beetles,
      Callosobruchus chinensis (L.) and Callosobruchus maculatus (F.) (Coleoptera:
      Bruchidae).
AB  - The bruchid beetle, Callosobruchus chinensis (L.) and C. maculatus (F.)
      (Coleoptera: Bruchidae), are important stored-product insects of stored legume
      seeds. In this study, the external morphologies of the antennal sensilla on the
      antennae of both female and male adults of these two species were described using
      scanning electron microscopy. Antennae of both species are made up of the scape,
      pedicel, and nine segments of flagellomeres. Antennae of female and male C.
      maculatus and female of C. chinensis are serrate in shape, while those of male C.
      chinensis are pectinate. Eight morphological sensilla types were recorded in both
      sexes, including Bohm bristles (BB), two types of sensilla trichoid (ST1, ST2),
      sensilla chaetica (SC), two types of sensilla basiconic (SB1, SB2), grooved pegs
      (GP), and sensilla cavity (SCa). The number of ST1 and SB1 of the male were
      significantly greater than those of the female of C. chinensis, and the number of
      ST2 and SB1 of the male were significantly more abundant than those of the female
      of C. maculatus. The possible functions of the above sensilla types are discussed
      in light of previously published literature.

PMID- 19101161
TI  - Interactions of peripheral-type benzodiazepine receptor with diamino acid
      derivatives of protoporphyrin IX.
AB  - The aim of this study was to examine and determine binding affinities of the
      peripheral benzodiazepine receptor (PBR) with diamino acid derivatives of
      protoporphyrin IX with general structure PP(AA)(2) in a function of environmental
      pH changes. Fluorescence intensity was used as a measure of protein association
      constant. Decrease in protein fluorescence, after titration with increasing
      concentration of porphyrins, gave evidence of interactions between PBR and
      examined ligands. Experimental data were fitted to theoretical curves, assuming
      different models of interactions. All examined ligands were best fitted to weak
      binding model. Increase in environmental acidity resulted in changes in
      association constants. For all examined derivatives association constants were at
      least twice higher in pH 5.5 as compared to pH 7.4 and 6.5.

PMID- 19101162
TI  - DNA damage after phototherapy in wounded fibroblast cells irradiated with 16
      J/cm(2).
AB  - BACKGROUND AND OBJECTIVE: Phototherapy or biomodulation is a remarkable therapy
      that has become more popular and widely used in the treatment of a variety of
      medical conditions, such as slow to heal wounds, pain, soft tissue injuries and
      skin trauma. It has been shown to induce DNA damage; however this damage appears
      to be repairable. This study aimed to determine the effects of phototherapy
      induced DNA damage and activation of the DNA repair gene methylpurine DNA
      glycosylase (MPG). MATERIALS AND METHODS: DNA integrity was assessed using the
      comet assay, with and without formamidopyrimidine glycosylase (Fpg). For the
      comet assay, wounded human skin fibroblast cells (WS1) were irradiated twice,
      once at 30 min and again at 72 h with 5 or 16 J/cm(2) using a diode laser at 636
      nm and cellular responses were assessed 1 or 24h post-irradiation. Real time
      reverse transcriptase polymerase chain reaction (RT-PCR) assessed MPG expression
      and three reference genes namely; beta Actin (ACTB), Glyceraldehyde three
      phosphate dehydrogenase (GAPDH) and Ubiquitin c (UBC). Wounded cells were
      irradiated once (30 min) with 16 J/cm(2), and MPG expression was assessed at 0, 3
      and 8h post-laser irradiation. RESULTS: At both 1 and 24h, wounded cells
      irradiated with 5 J/cm(2) showed insignificant DNA damage compared to control
      cells, while irradiation with 16 J/cm(2) showed significant damage. However, 24h
      post-irradiation these cells showed a significant decrease in damage compared to
      cells left to incubate for 1h. This observation was attributed to activation of
      DNA repair mechanisms. Real time RT-PCR showed that ACTB was not influenced by
      cell culture conditions or laser irradiation, and MPG expression was not
      detected. CONCLUSION: In conclusion, irradiation with 5 J/cm(2) did not produce
      additional DNA damage, while damage to cells irradiated with 16 J/cm(2) was
      repairable by mechanisms other than MPG. This study also showed that ACTB can be
      used as a reference gene in laser experiments, using parameters set out in this
      study.

PMID- 19101163
TI  - Full-scan accurate mass selectivity of ultra-performance liquid chromatography
      combined with time-of-flight and orbitrap mass spectrometry in hormone and
      veterinary drug residue analysis.
AB  - The applicability of ultra-performance liquid chromatography (UPLC) combined with
      full-scan accurate mass time-of-flight (TOF) and Orbitrap mass spectrometry (MS)
      to the analysis of hormone and veterinary drug residues was evaluated. Extracts
      from blank bovine hair were fortified with 14 steroid esters. UPLC-Orbitrap MS
      performed at a resolving power of 60,000 (FWHM) enabled the detection and
      accurate mass measurement (<3 ppm error) of all 14 steroid esters at low ng/g
      concentration level, despite the complex matrix background. A 5 ppm mass
      tolerance window proved to be essential to generate highly selective
      reconstructed ion chromatograms (RICs) having reduced background from the hair
      matrix. UPLC-Orbitrap MS at a lower resolving power of 7500 and UPLC-TOFMS at
      mass resolving power 10,000 failed both to detect all of the steroid esters in
      hair extracts owing to the inability to mass resolve analyte ions from co-eluting
      isobaric matrix compounds. In a second application, animal feed extracts were
      fortified with coccidiostats drugs at levels ranging from 240 to 1900 ng/g. UPLC
      Orbitrap MS conducted at a resolving power of 7500 and 60,000 and UPLC-TOFMS
      detected all of the analytes at the lowest investigated level. Thanks to the
      higher analyte-to-matrix background ratio, the utilization of very narrow mass
      tolerance windows in the RIC was not required. This study demonstrates that even
      when the targeted sample preparation from conventional LC-MS/MS is applied to
      UPLC with full-scan accurate mass MS, false compliant (false negative) results
      can be obtained when the mass resolving power of the MS is insufficient to
      separate analyte ions from isobaric co-eluting sample matrix ions. The current
      trend towards more generic and less selective sample preparation is expected to
      aggravate this issue further.

PMID- 19101164
TI  - Gas-phase H/D exchange and collision cross sections of hemoglobin monomers,
      dimers, and tetramers.
AB  - The conformations of gas-phase ions of hemoglobin, and its dimer and monomer
      subunits have been studied with H/D exchange and cross section measurements.
      During the H/D exchange measurements, tetramers undergo slow dissociation to
      dimers, and dimers to monomers, but this did not prevent drawing conclusions
      about the relative exchange levels of monomers, dimers, and tetramers. Assembly
      of the monomers into tetramers, hexamers, and octamers causes the monomers to
      exchange a greater fraction of their hydrogens. Dimer ions, however, exchange a
      lower fraction of their hydrogens than monomers or tetramers. Solvation of
      tetramers affects the exchange kinetics. Solvation molecules do not appear to
      exchange, and solvation lowers the overall exchange level of the tetramers. Cross
      section measurements show that monomer ions in low charge states, and tetramer
      ions have compact structures, comparable in size to the native conformations in
      solution. Dimers have remarkably compact structures, considerably smaller than
      the native conformation in solution and smaller than might be expected from the
      monomer or tetramer cross sections. This is consistent with the relatively low
      level of exchange of the dimers.

PMID- 19101166
TI  - Invariable H-reflex and sustained facilitation of stretch reflex with heightened
      sympathetic outflow.
AB  - Stretch reflex shows sustained (3-min) increase with heightened sympathetic
      outflow [Hjortskov N, Skotte J, Hye-Knudsen C, Fallentin N. Sympathetic outflow
      enhances the stretch reflex response in the relaxed soleus muscle in humans. J
      Appl Physiol 2005;98:1366-70], but it is unknown if it accompanies a sustained
      increase in H-reflex. The purpose of the study was to test if there is a
      sustained facilitation in the H-reflex in the human soleus muscle during a
      variety of sustained tasks that are known to elevate sympathetic outflow. Mean
      arterial blood pressure, heart rate, and H- and stretch reflexes in the relaxed
      soleus muscle were obtained in healthy young adults who performed mental
      arithmetic, static handgrip exercise, post-handgrip ischemia, and cold
      stimulation. Each task lasted 3 min with a 3-min rest in between tasks. Data were
      analyzed for the initial 30 s and entire 3 min of each task. There was a
      heightened cardiovascular response in all tasks for both durations of analysis.
      An increase in H-reflex amplitude was not observed for either the initial or
      entire duration of the analysis. The tasks increased stretch reflex amplitude for
      both durations of analysis. Invariable H-reflex and sustained facilitation of
      stretch reflex with heightened sympathetic outflow would imply sympathetic
      modulation of muscle spindle sensitivity.

PMID- 19101165
TI  - Increasing charge while preserving noncovalent protein complexes for ESI-MS.
AB  - Increased multiple charging of native proteins and noncovalent protein complexes
      is observed in electrospray ionization (ESI) mass spectra obtained from
      nondenaturing protein solutions containing up to 1% (vol/vol) m-nitrobenzyl
      alcohol (m-NBA). The increases in charge ranged from 8% for the 690 kDa
      alpha(7)beta(7)beta(7)alpha(7) 20S proteasome complex to 48% additional charge
      for the zinc-bound 29 kDa carbonic anhydrase-II protein. No dissociation of the
      noncovalently bound ligands/subunits was observed upon the addition of m-NBA. It
      is not clear if the enhanced charging is related to altered surface tension as
      proposed in the "supercharging" model of Iavarone and Williams (Iavarone, A. T.;
      Williams, E. R. J. Am. Chem. Soc.2003, 125, 2319-2327). However, more highly
      charged noncovalent protein complexes have utility in relaxing slightly the mass
      to-charge (m/z) requirements of the mass spectrometer for detection and will be
      effective for enhancing the efficiency for tandem mass spectrometry studies of
      protein complexes.

PMID- 19101167
TI  - Shoulder and elbow muscle activity during fully supported trajectory tracking in
      neurologically intact older people.
AB  - An inability to perform tasks involving reaching is a common problem for stroke
      patients. Knowledge of normal muscle activation patterns during these tasks is
      essential to the identification of abnormal patterns in post-stroke hemiplegia.
      Findings will provide insight into changes in muscle activation patterns
      associated with recovery of upper limb function. In this study with
      neurologically intact participants the co-ordination of shoulder and elbow muscle
      activity during two dimensional reaching tasks is explored. Eight participants
      undertook nine tracking tasks in which trajectory (orientation and length),
      duration, speed and resistance to movement were varied. The participants' forearm
      was supported using a hinged arm-holder, which constrained their hand to move in
      a two dimensional plane. EMG signals were recorded from triceps, biceps, anterior
      deltoid, upper, middle and lower trapezius and pectoralis major. A wide variation
      in muscle activation patterns, in terms of timing and amplitude, was observed
      between participants performing the same task. EMG amplitude increased
      significantly with length, duration and resistance of the task for all muscles
      except anterior deltoid. Co-activation between biceps and triceps was
      significantly dependent on both task and trajectory orientation. Activation
      pattern of pectoralis major was dependent on trajectory. Neither trajectory
      orientation nor task condition affected the activation pattern of anterior
      deltoid. Normal ranges of timing of muscle activity during the tasks were
      identified.

PMID- 19101168
TI  - A mysterious echogenic structure in the left atrium after coronary artery bypass
      graft surgery.

PMID- 19101170
TI  - A rare cause of mitral regurgitation in an elderly man undergoing aortic valve
      replacement.

PMID- 19101169
TI  - Levosimendan may prevent postoperative atrial fibrillation through anti
      inflammatory and antioxidant modulation.

PMID- 19101171
TI  - Left main bronchial lavage with normal saline under fluoroscopy improved
      pulmonary mechanics in a neonate after the Damus-Kaye-Stansel procedure.

PMID- 19101172
TI  - Lipoma of the supraspinatus muscle causing impingement syndrome: a case report.

PMID- 19101173
TI  - Intraobserver and interobserver agreement of International Classification of
      Diseases, Ninth Revision codes in classifying shoulder instability.
AB  - HYPOTHESIS: The purpose of this study was to investigate the intraobserver and
      interobserver reliability of the International Classification of Diseases, Ninth
      Revision (ICD-9) system when applied to the classification of shoulder
      instability. MATERIALS AND METHODS: From December 2005 through February 2007, 50
      patients with shoulder instability were evaluated and classified by an attending
      physician using one of the 16 ICD-9 codes for shoulder instability. Patients were
      reassessed after two weeks by the original physician and two additional shoulder
      specialists. 42 patients completed the study. These data were then analyzed to
      assess intraobserver and interobserver reliability. RESULTS: Intraobserver
      agreement for ICD-9 codes was 50% (kappa=0.25, fair). Interobserver agreement was
      23% (kappa=0.002, poor). DISCUSSION: The ICD-9 coding system is the recognized
      standard for classifying disease states and is used for large epidemiologic
      studies. The poor agreement demonstrated in this study suggests that the ICD-9
      coding system has poor agreement and as such is not a precise method to classify
      shoulder instability. CONCLUSION: Shoulder instability cannot reliably be
      classified using the ICD-9 coding system. Until a more reliable system is
      developed, epidemiologic studies of shoulder instability that use ICD-9 codes may
      be difficult to interpret. LEVEL OF EVIDENCE: Level 1; Testing a previously
      developed classification system.

PMID- 19101174
TI  - Osteosynthesis and hemiarthroplasty of fractures of the proximal humerus:
      outcomes in a consecutive case series.
AB  - HYPOTHESIS: This study addresses the outcome after osteosynthesis or
      hemiarthroplasty, using a cohort of patients that was enrolled in a previous
      prospective study on humeral head perfusion and was consequently treated using a
      common conceptual approach. MATERIALS AND METHODS: Between 1998 and 2001, 98
      patients with 100 fractures of the proximal humerus were treated surgically by a
      single surgeon with open reduction and internal fixation (ORIF) (51/100, group A,
      median age 54 years; range, 21-88) or with hemiarthroplasty (49/100, group B,
      median age 66 years; range, 38-87). Seventy-six of 98 patients were available for
      re-evaluation at a mean follow-up of five years (3.3-7.3) using the Constant
      Murley score (CMS), the Subjective Shoulder Value (SSV), and conventional
      radiographs. RESULTS: The median total CMS was 77 (range, 37-98) for group A and
      70 (range, 39-84) for group B. The median SSV was 92 (range, 40-100) for group A
      and 90 (range, 40-100) for group B. Avascular necrosis occured in 6/40 fractures
      treated with ORIF. CONCLUSION: Osteosynthesis and hemiarthroplasty yield similar
      functional results and comparable patient satisfaction following the applied
      decision making process in this selected patient cohort. Osteosynthesis with
      preservation of the humeral head is worth considering when adequate reduction and
      stable conditions for revascularization can be obtained. In patients with
      osteopenic bone and/or comminuted fractures, hemiarthroplasty is a viable
      alternative. LEVEL OF EVIDENCE: Level 2; Prospective non-randomized comparison
      study.

PMID- 19101175
TI  - Reverse shoulder arthroplasty as salvage procedure after deltoid muscle flap
      transfer for irreparable rotator cuff tear: a case report.

PMID- 19101176
TI  - Surgical management of a periprosthetic fracture between a total elbow and total
      shoulder prostheses: a case report.

PMID- 19101177
TI  - Functional outcome after repair of distal biceps tendon ruptures using the
      endobutton technique.
AB  - HYPOTHESIS: The purpose of this study is to report the functional outcome of the
      repair of a distal biceps tendon rupture by the use of the endobutton technique.
      We hypothesized that the endobutton provides excellent strength and clinical
      results after repair of distal biceps tendon rupture. MATERIALS AND METHODS:
      Twenty-six patients underwent repair of biceps tendon ruptures by use of an
      endobutton for fixation of the biceps tendon stump to the radial tuberosity.
      There were 20 men and three women. The mean age was 52 years (39-75). The
      dominant side was involved in 11 patients. A partial rupture of the biceps tendon
      was found in four patients. The average delay in diagnosis was 16 days, with four
      patients presenting at six weeks or more after trauma. RESULTS: At an average
      follow-up of 16 months (6-48), 23 of 26 patients were available for follow-up and
      were examined clinically, radiologically, and by isokinetic testing. The average
      postoperative Mayo Elbow Performance Score (MEPS) was 94 points. The average
      Visual Analogue Scale (VAS) for pain was 1.5. Patients regained an almost full
      range of motion. Average flexion strength recovery was 80% and corresponding
      recovery of supination strength was 91%. Two patients developed asymptomatic
      heterotopic ossification seen on standard radiographs. In three patients, the
      endobutton had apparently disengaged without important difference in functional
      outcome. In one case, the endobutton had to be removed. There were no
      neurological complications. CONCLUSION: This study shows that a distal biceps
      tendon can be safely reattached to the radius by using the endobutton technique,
      yielding excellent and reproducible results. LEVEL OF EVIDENCE: Level 4;
      Retrospective case series, no control group.

PMID- 19101178
TI  - Frontal-onset absences in children: associated with worse outcome? A replication
      study.
AB  - We studied the clinical and electroencephalographic features in 30 children who
      were diagnosed with childhood absence epilepsy. According to their EEG pattern we
      divided the 30 children into two groups: group A: 11 children with classical
      absences whose ictal EEG showed primary generalized spikes and waves and group B:
      19 children with frontal onset of the EEG epileptic abnormalities ('frontal
      group'). In the frontal group, more frequently complex absences were seen.
      Although the majority of children responded very well to valproate monotherapy,
      ethosuximide has to be added in 3 children of the frontal group to achieve
      seizure freedom. In the frontal group, also more learning and behavioural
      problems were encountered. This study largely confirms a previous study of Lagae
      et al. [Lagae L, Pauwels J, Monte B, Verhelle J, Vervisch J. Frontal absences in
      children. Eur J Pediatr Neurol 2001;5:243-251]. It seems that frontal onset
      absences constitute a specific subtype within the childhood absence epilepsies.

PMID- 19101179
TI  - Preclinical animal models in single site cartilage defect testing: a systematic
      review.
AB  - OBJECTIVE: Review the literature for single site cartilage defect research and
      evaluate the respective strengths and weaknesses of different preclinical animal
      models. METHOD: A literature search for animal models evaluating single site
      cartilage defects was performed. Variables tabulated and analyzed included animal
      species, age and number, defect depth and diameter and study duration. Cluster
      analyses were then used to separate animals with only distal femoral defects into
      similar groups based on defect dimensions. Representative human studies were
      included allowing comparison of common clinical lesions to animal models. The
      suitability of each species for single site cartilage defect research and its
      relevance to clinical human practice is then discussed. RESULTS: One hundred
      thirteen studies relating to single site cartilage defects were reviewed. Cluster
      analysis included 101 studies and placed the murine, laprine, ovine, canine,
      porcine and caprine models in group 1. Group 2 contained ovine, canine, porcine,
      caprine and equine models. Group 3 contained only equine models and humans.
      Species in each group are similar with regard to defect dimensions. Some species
      occur in multiple groups reflecting utilization of a variety defect sizes. We
      report and discuss factors to be considered when selecting a preclinical animal
      model for single site cartilage defect research. DISCUSSION: Standardization of
      study design and outcome parameters would help to compare different studies
      evaluating various novel therapeutic concepts. Comparison to the human clinical
      counterpart during study design may help increase the predictive value of
      preclinical research using animal models and improve the process of developing
      efficacious therapies.

PMID- 19101180
TI  - The occurrence of cpb2-toxigenic Clostridium perfringens and the possible role of
      the beta2-toxin in enteric disease of domestic animals, wild animals and humans.
AB  - The virulence of Clostridium perfringens, a bacterium causing enteritis and
      enterotoxaemia in domestic and wild animals and humans, results largely from its
      ability to produce toxins. In 1997, an unknown toxin of C. perfringens, the beta2
      toxin, and its encoding gene cpb2 were described. Since that time numerous
      studies have been published dealing with a possible association of cpb2
      harbouring strains of C. perfringens and the occurrence of enteric disease in
      domestic and wild animals and humans. This article offers an overview of the
      current literature on the spread and pathological significance of cpb2-harbouring
      C. perfringens. Unambiguous conclusions on the prevalence of cpb2 and the
      contribution of beta2-toxin to the disease cannot be drawn from existing studies
      but in some animal species a strong correlation between the presence of cpb2
      harbouring C. perfringens, the beta2-toxin and enteric disease has been reported.

PMID- 19101181
TI  - Cortical changes in complex regional pain syndrome (CRPS).
AB  - Recent research suggests that changes in cortical structures can contribute to
      the pathophysiology of Complex Regional Pain Syndrome (CRPS). This review
      provides an overview of studies showing cortical involvement in CRPS, including
      mislocalizations of tactile stimuli, changes in size and organization of the
      somatosensory map, changes in motor cortex representation and body perception
      disturbances. In addition, we review experimental treatment approaches, such as
      mirror therapy and motor imagery programs, aimed at restoring the integrity of
      neural processing in the sensory-motor cortex in individuals with CRPS. The
      intervention effects are promising and can be theoretically motivated on the
      basis of established principles of neural organization, although important
      questions concerning the precise neural mechanisms of action remain unanswered.

PMID- 19101182
TI  - Fear-avoidance- and endurance-related responses to pain: development and
      validation of the Avoidance-Endurance Questionnaire (AEQ).
AB  - AIM OF INVESTIGATION: Recent research indicated wide variability regarding pain
      related cognitive/affective and behavioral responses to pain, showing that fear
      avoidance responses (FAR) and endurance-responses (ER) play a prominent role in
      the maintenance of low back pain (LBP). Until now, there is a lack of reliable
      and valid instruments covering FAR and ER. METHODS: A pool of 60 items, derived
      from the Kiel Pain Inventory was answered by 191 LBP patients. Principle
      components analyses (PCA) was used to explore the factor structure creating the
      Avoidance-Endurance Questionnaire (AEQ). Validity was calculated using the
      criteria variables pain intensity, disability, chronic pain grades (CPG) and
      number of sick days, further self-report measures (Fear-Avoidance Beliefs
      Questionnaire FABQ, Pain Anxiety Symptoms Scale PASS, Tampa Scale of
      Kinesiophobia TSK and Beck Depression Inventory BDI) evaluating construct
      validity. RESULTS: PCA revealed five AEQ-FAR scales with anxiety/depression,
      catastrophizing, help-/hopelessness, avoidance of social activities, avoidance of
      physical activities, and four AEQ-ER scales with positive mood, thought
      suppression, pain persistence behavior and humor/distraction. All scales revealed
      high internal consistency. As expected, FAR scales showed positive associations
      with pain, disability and other FAR variables (correlations between r=.26 and
      r=.58), whereas ER scales showed negative associations (between r=-.19 and -.48).
      The only exception referred to positive correlations between both, FAR and ER and
      pain intensity. CONCLUSIONS: The AEQ has shown as a reliable and valid measure to
      assess pattern of fear-avoidance and endurance-related responses to pain. Both
      aspects seem to play a role in the maintenance of LBP.

PMID- 19101183
TI  - Assessing the performance of windowed 1H CRAMPS methods, on biological solids, at
      high-field and MAS up to 35 kHz.
AB  - The performance of various high-resolution 1D (1)H CRAMPS pulse schemes at
      moderate and high static magnetic fields (400 MHz and 800 (1)H Larmor
      frequencies) and spinning rates up to 35 kHz, using state-of-the-art electronics
      is compared. The performance of the (1)H windowed acquisition decoupling schemes,
      wDUMBO, wPMLG3 and wSAM3 is investigated using their effective z-rotation
      variants on glycine and other small biological molecules, tripeptide reduced
      glutathione and nucleoside uridine. (1)H CRAMPS spectra, recorded with windowed
      (1)H-(1)H decoupling methods and fast MAS (35 kHz) and high-field are reported
      for the first time. (1)H spectra exhibiting outstanding resolution and completely
      free from any artifact are also shown. The effect on spectra quality of the
      decoupling rf cycle and rotor periods ratio (tau(C)/tau(R)) and the power
      requirements needed for each windowed (1)H CRAMPS methods are discussed.

PMID- 19101184
TI  - Heteronuclear dipolar recoupling in multiple-spin system under fast magic-angle
      spinning.
AB  - We show that the C-REDOR sequence can be modified according to the framework of
      rotary-REDOR to realize heteronuclear recoupling in multiple-spin systems.
      Because of the inherent favorable properties of C-REDOR with respect to rf
      inhomogeneity, our approach is anticipated to find useful applications in
      biological research. Furthermore, active rotor synchronization of the windowless
      C-REDOR is implemented by an ad hoc shortening of the pulse elements. Numerical
      simulations and experiments measured for [U-(13)C,(15)N]-L-alanine are used to
      validate our approach.

PMID- 19101185
TI  - First structurally characterized mixed-halogen nickel(III) NCN-pincer complex.
AB  - A square-pyramidal mixed-halogen nickel(III) NCN-pincer complex (PipeNCN)NiClBr
      (where PipeNCN=2,6-bis(piperidinomethyl)phenyl) was structurally characterized.
      Bromine occupies apical position; pincer ligand and chlorine atom are in the
      basal plane. EPR detects that complex in solution exists as a mixture of two
      structural isomers with bromine or chlorine atoms in the top of pyramid.

PMID- 19101186
TI  - Inter- and intramolecular contacts in a membrane protein/surfactant complex
      observed by heteronuclear dipole-to-dipole cross-relaxation.
AB  - Heteronuclear dipole-to-dipole cross-relaxation has been applied to exploring
      intermolecular interactions and intramolecular spatial proximities in a large
      supramolecular structure comprised of a beta-barrel membrane protein, OmpX, in
      complex with a polymeric surfactant, amphipol A8-35. The experiments, performed
      in either the laboratory or the rotating frame, reveal the existence of
      intermolecular contacts between aromatic amino acids and specific groups of the
      polymer, in addition to intra-protein dipolar interactions, some of them
      involving carbonyl carbons. This study opens the perspective of collecting by NMR
      spectroscopy a new kind of through-space structural information involving
      aromatic and carbonyl (13)C atoms of large proteins.

PMID- 19101188
TI  - State of the art and challenges of time-of-flight PET.
AB  - After a brief review of the history of time-of-flight (TOF) positron emission
      tomography (PET) instrumentation from the 1980s to present, the principles of TOF
      PET are introduced, the concept of time resolution and its effect on TOF gain in
      signal-to-noise ratio (SNR) are discussed. The factors influencing the time
      resolution of a TOF PET scanner are presented, with focus on the intrinsic
      properties of scintillators of particular interest for TOF PET. Finally, some
      open issues, challenges and achievements of today's TOF PET reconstruction are
      reviewed: the structure of the data organization, the choice of analytical or
      iterative method, the recent experimental assessment of TOF image quality, and
      the most promising applications of TOF PET.

PMID- 19101187
TI  - Intravitreal bevacizumab and triamcinolone treatment for choroidal
      neovascularization in Best disease.
AB  - An 11-year-old girl with active subfoveal choroidal neovascularization associated
      with Best disease responded well to a single intravitreal injection of combined
      bevacizumab and triamcinolone acetonide. Choroidal neovascularization regressed,
      subretinal serous fluid resorbed, and visual acuity improved from 20/400 to
      20/100. The patient remained stable for 6 months after injection.

PMID- 19101189
TI  - Hypercholesterolaemia in anorexia nervosa: frequency and changes during
      refeeding.
AB  - High total cholesterol (TC) is common in patients with anorexia nervosa (AN), but
      its mechanisms remain unclear. PATIENTS AND METHODS: We prospectively studied
      plasma lipoprotein (LP), haptoglobin, free (f) T3, fT4, TSH, transthyretin and
      albumin in 120 malnourished adult AN patients (BMI: 13.5+/-1.5 kg/m(2)), 116 non
      AN malnourished patients and 119 healthy subjects, matched for age and gender.
      RESULTS: In 18% of our AN patients, TC was higher than 270 mg/100mL (in non-AN:
      5%; P<0.01). TC, low-density lipoprotein cholesterol (LDL-C), high-density
      lipoprotein cholesterol (HDL-C) and HDL2 levels were higher in AN patients than
      in non-AN patients (P<0.001). Low TC (<150 mg/100mL) and LP levels were observed
      in 8% of AN patients, but only when BMI was less than 13 kg/m(2). Cholesterol
      ester transfer protein (CETP) activity was higher in AN patients than in healthy
      subjects. LP was positively correlated with BMI, albumin, fT3 and haptoglobin
      levels. In AN patients, there was a biphasic LP profile (low values when BMI was
      very low, normal values in an intermediate state, and high values when BMI was
      highest and where bulimia was also present). CONCLUSION: In AN, both high and low
      cholesterol-rich LP levels were observed. Low T3 and low catabolism allow LP to
      be maintained, while CETP activity increases cholesterol turnover as an
      adaptation to its low intake. In severely malnourished AN patients, this fails
      and LP drops. On the other hand, LP values were higher in the bingeing-purging
      type of AN than in the restrictive type. Recovery from AN results in the
      normalization of the LP profile.

PMID- 19101190
TI  - Chronic lipoic acid treatment worsens energy imbalances in streptozotocin-induced
      diabetic rats.
AB  - AIM: Our objective was to verify the energy balance in streptozotocin-induced
      diabetic rats chronically treated with lipoic acid (LA). METHODS: Diabetes was
      induced in rats by streptozotocin and the animals divided into four groups,
      comprising controls and diabetic rats, with each group receiving either daily
      intraperitoneal LA (30 mg/kg) or a buffer solution for 30 days. Body weight, food
      intake and stool and urine collections were recorded daily. On day 30, animals
      were sacrificed and the carcasses, faeces and urine collected and processed for
      calorimetric analysis. Blood glucose and insulin were also determined. RESULTS:
      All parameters of energy balance were affected by diabetes. LA treatment reduced
      weight gain, energy gain and gross food efficiency in both control and diabetic
      animals. However, the LA-treated animals tended to show higher energy expenditure
      than non-treated animals. Body composition was also affected by diabetes: fat
      content was impaired by LA treatment in both control and diabetic animals. The
      latter also showed increased glycaemia and decreased insulinaemia, but LA had no
      effect on these parameters. CONCLUSION: Our results indicate that chronic
      treatment with LA aggravates energy imbalances in diabetic animals. Moreover, our
      data suggest the need to reconsider the use of LA as an adjuvant in the
      prevention and treatment of type 1 diabetes.

PMID- 19101191
TI  - [MALT lymphoma of the rectum: a case report treated by radiotherapy].
AB  - The mucosa-associated lymphoid tissue (MALT) lymphoma is a distinct clinical
      pathologic entity that develops in diverse anatomic locations such as the
      stomach, salivary gland, thyroid, lung, skin and breast. However, colorectal
      involvement is extremely rare. To our knowledge, only ten cases of primary rectal
      MALT lymphoma have been reported in the literature. We report a 46-year-old woman
      with rectal MALT lymphoma, which regressed after radiotherapy. The patient had
      rectal bleeding. Colonoscopy showed a pseudonodular and ulcerated big fold in the
      rectum. Microscopic and immunohistologic studies of the biopsy specimen showed
      typical features of low grade MALT lymphoma. Upper endoscopy showed chronic
      gastritis with lymphoid follicles but without any infiltration of lymphoma cells.
      Helicobacter pylori infection was confirmed by histology. No extra-intestinal
      involvement was found on the staging evaluation, which included computed
      tomography (CT) of the abdomen, chest, pelvis and a bone marrow biopsy. We
      attempted to eradicate H. pylori with a 7-day course of omeprazole, amoxycillin,
      and metronidazole. Eradication was proved successful by endoscopy. Repeated
      colonoscopy 4 months after the end of treatment showed that the rectal tumor had
      not regressed. Biopsy specimens confirmed the persistent infiltration of lymphoma
      cells. The patient was considered to be a non-responder to eradication therapy
      and was indicated for radiotherapy. He underwent a total of 34 Gy. Complete
      regression was confirmed by colonoscopic and histologic examination at 2 months
      after the end of treatment. He was followed up closely with colonoscopy, but no
      relapse of these lesions was detected after 12 months.

PMID- 19101193
TI  - Crystal structures and spectroscopic properties of ester amide and diamide of
      squaric acid with prolinamide.
AB  - We report the synthesis, spectroscopic and structural elucidation of two
      prolinamide derivatives of squaric acid, i.e. prolinamide ester amide of squaric
      acid ethyl ester (1) and prolinamide diamide of squaric acid dihydrate (2). Both
      compounds crystallize in non-centrosymmetric space groups, monoclinic P2(1) (1)
      and orthorhombic P2(1)2(1)2(1) (2), respectively. For first time in the
      literature the crystal structure of homodiamide of amino acid amide of squaric
      acid is reported. The data for heterodiamides is also absent. Supramolecular zig
      zag chains by hydrogen bonds of H(2)N-C=O ..., HNH (3.020 A) and HNH ...,
      OC((S(q))) (2.972 A) types with the participation of amide and squaric acid
      (S(q)) fragments, -CO=NH(2) and O=C((S(q))) are refined in (1). A helix
      supramolecular structure is formed in (2) by moderate intermolecular HNH ...
      O=C(NH(2)) hydrogen bond with length of 2.947A. The two crystallographical non
      equivalent water molecules stabilized the helix by interactions of types
      HOH...OC((Sq)) (2.917A), HOH...O=C(NH(2)) (2.899A), H(2)O...NH(2)(C=O) (2.972A),
      respectively. Optical and magnetic properties are investigated with a view to
      explain the correlation structure-properties of the newly synthesized molecules.

PMID- 19101192
TI  - [A rare case of primitive prostatic large B-cell lymphoma and review of
      literature].
AB  - Primary malignant non-hodgkin lymphoma involving the prostate is rare. Most of
      the time, it is associated with extraprostatic disease. We report a case of a 72
      year-old patient presenting with acute lower urinary tract irritative symptoms,
      due to large B-cell lymphoma limited to the prostate. Combination of chemotherapy
      with extern beam radiotherapy provided long-term local control.

PMID- 19101194
TI  - Synthesis, characterization, DNA interaction and cytotoxic activities of copper
      complexes with ethyl 2-[bis(2-pyridylmethyl)amino]propionate.
AB  - Copper(II) complexes of ethyl 2-[bis(2-pyridylmethyl)amino]propionate ligand
      (ETDPA) have been synthesized and characterized by elemental analyses, IR
      spectra, UV spectra and ES-MS. These complexes are stable in air with the formula
      of [(ETDPA)CuCl(2)] and [(ETDPA)Cu(phen)](ClO(4))(2). The DNA-binding properties
      of the Cu(II) complexes have been investigated by ultraviolet spectroscopy and
      fluorescence spectroscopy, which showed that the binding mode of the two
      complexes with DNA was different. The binding mode of [(ETDPA)CuCl(2)] is not the
      classical intercalation binding, and the binding mode of
      [(ETDPA)Cu(phen)](ClO(4))(2) with DNA is intercalation. The cytotoxic assay shows
      that the [(ETDPA)Cu(phen)](ClO(4))(2) is more active on the proliferation of
      cancer cells than the [(ETDPA)CuCl(2)].

PMID- 19101195
TI  - Tm(3+)/Yb(3+)co-doped tellurite glass for broadband optical amplifying over S+L
      bands.
AB  - A kind of novel fluorescence which possesses a potential application in wide-band
      optical amplifying is reported in this paper. With 975-nm LD laser pumping and
      Yb(3+)-assisted energy transferring, the fluorescence of Tm(3+)in the tellurite
      glass can be measured with emission spectra in 1.4- and 1.6- microm bands, which
      would be continued to the 1.53 microm of the Er(3+). The full-width at half
      maximum (FWHM) is 170 nm(110 + 60nm), and the lifetimes come up to 0.66 and 1.46
      ms. Then, an interpretation was given to the mechanism of IR fluorescence
      emission which is based on the energy transferring and up-conversion of Tm(3+),
      Yb(3+) and Er(3+).

PMID- 19101196
TI  - Characterization and electrochemical studies of Mn(II), Co(II), Ni(II) and Cu(II)
      complexes with 2-mercapto-3-substituted-quinazolin-4-one and 1,10-phenanthroline
      or ethylenediamine as ligands.
AB  - Some mixed ligand complexes of the type [M(L(1) or L(2))(phen or en)(H(2)O)Cl],
      where M=Mn(II), Co(II), Ni(II) and Cu(II); HL(1)=2-mercapto-quinazolin-4-one;
      HL(2)=2-mercapto-3-phenyl-quinazolin-4-one; phen=1,10-phenanthroline;
      en=ethylenediamine have been prepared. All complexes were characterized on the
      basis of elemental analysis, molar conductance, magnetic susceptibility
      measurements, IR, UV-vis, ESR and powder X-ray diffraction studies. IR spectra of
      these complexes reveal that the complex formation occurred through both nitrogen
      and sulphur atoms. On the basis of electronic spectral data and magnetic
      susceptibility measurement octahedral geometry has been proposed for the
      complexes. The ESR spectral data of the Cu(II) complexes showed that the metal
      ligand bonds have considerable covalent character. X-ray diffraction studies of
      Cu(II) complexes are used to elucidate the crystal structure. The electrochemical
      behaviour of mixed ligand Ni(II) complexes was studied which showed that
      complexes of phen appear at more positive potential as compared to those for
      corresponding en complexes.

PMID- 19101197
TI  - Human factors engineering in healthcare systems: the problem of human error and
      accident management.
AB  - This paper discusses some crucial issues associated with the exploitation of data
      and information about health care for the improvement of patient safety. In
      particular, the issues of human factors and safety management are analysed in
      relation to exploitation of reports about non-conformity events and field
      observations. A methodology for integrating field observation and theoretical
      approaches for safety studies is described. Two sample cases are discussed in
      detail: the first one makes reference to the use of data collected in the
      aviation domain and shows how these can be utilised to define hazard and risk;
      the second one concerns a typical ethnographic study in a large hospital
      structure for the identification of most relevant areas of intervention. The
      results show that, if national authorities find a way to harmonise and formalize
      critical aspects, such as the severity of standard events, it is possible to
      estimate risk and define auditing needs, well before the occurrence of serious
      incidents, and to indicate practical ways forward for improving safety standards.

PMID- 19101198
TI  - Enterovirus genotyping directly from original clinical specimens: prospective
      application to a severe neonatal infection.

PMID- 19101199
TI  - Performance of a new immunochromatographic assay for detection of adenoviruses in
      children.
AB  - BACKGROUND: Adenoviruses are a prominent cause of respiratory, ocular,
      gastrointestinal, and disseminated diseases in healthy and immunocompromised
      children. An accurate rapid diagnostic assay may impact clinical decision-making.
      OBJECTIVES: Evaluate the performance of a new rapid assay for detection of
      adenoviruses directly in pediatric clinical specimens. STUDY DESIGN: The rapid
      assay was performed on adenovirus culture-positive original samples and on an
      equal number of culture-negative samples matched by patient age and specimen
      type. Discrepant results were resolved using a polymerase chain reaction (PCR)
      assay. RESULTS: 200 adenovirus culture-positive and 200 adenovirus culture
      negative samples were evaluated from 315 different patients. Overall sensitivity
      was 55% and specificity was 98.9%. The assay was most sensitive in children 5
      years old and younger and most specific in respiratory samples. CONCLUSIONS: The
      rapid assay was highly specific for detecting adenovirus infections in children.
      However, since this rapid assay had only moderate to low sensitivity, samples
      with negative rapid assay results should have additional testing for adenovirus
      performed by either viral culture or PCR.

PMID- 19101200
TI  - A longitudinal study of tremor frequencies in Parkinson's disease and essential
      tremor.
AB  - OBJECTIVE: There is evidence that the tremor frequency in essential tremor (ET)
      decreases with time. Longitudinal studies on the evolution of tremor frequencies
      in Parkinson's disease (PD) have so far not been published. Here, we present a
      longitudinal analysis of tremor frequencies in PD and ET. METHODS: We analyzed
      the standardized accelerometric and electromyographic tremor recordings of 53
      patients with PD and 38 patients with ET who underwent repeated routine tremor
      recordings between 1991 and 2002. RESULTS: In an average follow-up period of 44.9
      months in PD and 50.6 months in ET, the average number of tremor recordings was
      3.3 in PD and 3.7 in ET. In both disorders, tremor frequencies tended to decrease
      with time. The average annual decrease of the tremor frequency was 0.09 Hz/year
      in Parkinsonian rest tremor, 0.08 Hz/year in Parkinsonian postural tremor and
      0.12 Hz/year in ET. CONCLUSIONS: The tremor frequency decreases with time in both
      PD and ET. The similarity of this decrease in PD and ET may point to a common
      underlying pathophysiological mechanism. SIGNIFICANCE: Decreasing tremor
      frequencies with time may be functionally important by inducing larger tremor
      amplitudes due to the low-pass filtering properties of muscles and limbs.

PMID- 19101201
TI  - Combined cardiac sympathetic excitation and vagal impairment in patients with non
      organic erectile dysfunction.
AB  - OBJECTIVE: Patients with non-organic erectile dysfunction (ED) frequently present
      with syndromes involving systemic sympathovagal dysfunction. The linkage of ED to
      cardiac autonomic regulation is not well understood. METHODS: Forty-four men with
      non-organic ED and 38 healthy age-matched control subjects with ages ranging from
      40 years to 69 years were recruited. These two groups were divided into three
      distinct age categories at 10-year intervals. Patients were divided into three
      different severity categories, among whom 35 patients received a two-month oral
      treatment of trazodone. Power spectral analysis of successive R-R intervals (RR)
      was performed to evaluate the variance (variance of RR-interval values), the high
      frequency power (HF), and the ratio of low-frequency power to HF (LF/HF) of their
      heart rate variability (HRV). RESULTS: Patients exhibited a significantly lower
      variance and HF, but a higher LF/HF compared to the control group across all age
      categories. The changes in variance and HF were severity dependent. In addition,
      all the HRV parameters of the patients with a satisfactory response after
      treatment have significantly improved. CONCLUSION: The results indicate that
      patients with non-organic ED had significant cardiac sympathetic hyperactivity
      and severity-dependent cardiac vagal impairment. SIGNIFICANCE: Non-organic ED may
      be accompanied by an abnormality in cardiac autonomic regulation.

PMID- 19101202
TI  - Determining the time course of lexical frequency and age of acquisition using
      ERP.
AB  - OBJECTIVE: The main goal of the present study was to dissociate the effects on
      reading of frequency, age of acquisition (AoA) and imageability using the evoked
      response potential paradigm. METHOD: Twenty participants read words from three
      experimental conditions: high and low frequency, late and early age of
      acquisition and high and low imageability. RESULTS: High frequency words produced
      more positive mean amplitude than low frequency words in the 175-360 ms post
      stimulus onset time window and late AoA produced more negative amplitudes than
      early AoA in the 400-610 ms window. Imageability did not produce any effect in
      any time window tested. Brain electromagnetic tomography showed the most
      activated cortical areas for each category of stimuli. CONCLUSIONS: The lexical
      frequency of words seems to affect an early phase in the recognition process,
      perhaps at the level of the orthographic input lexicon, while AoA was observed at
      a later stage, indicating that this variable influence processing at a semantic
      level or at the links between semantics and phonology. SIGNIFICANCE: EEG permits
      the researcher to investigate the time course, and approximate location in the
      brain, of psycholinguistic variables.

PMID- 19101203
TI  - Effects of experimental focal compression on excitability of human median motor
      axons.
AB  - OBJECTIVE: To characterize the effect of focal compression by threshold tracking
      and other excitability measures of human median motor axons. METHODS: We
      conducted a sequence of excitability studies using a software written in BASIC
      (QTRAC version 4.0, (c)Institute of Neurology, London, UK, with multiple
      excitability protocol TRONDXM 2) in 24 healthy subjects, stimulating the median
      nerve at the wrist and recording compound muscle action potentials from the
      abductor pollicis brevis. Constant, localized compression was applied at the
      wrist by mechanically lowering a probe attached to a disk electrode, which also
      served as the stimulating cathode. RESULTS: Compared with the pre-compression
      values, measurements during compression showed a shift of threshold electrotonus
      waveforms toward the baseline (fanning-in), steeper current-threshold
      relationships, increased strength-duration time constants, prolonged relative
      refractory periods and reduced levels of superexcitability, but no alteration in
      late subexcitability. These excitability changes indicating depolarization
      reversed to hyperpolarization immediately after release of compression. The nerve
      compression altered none of the excitability measures when recorded 2 cm distally
      from the pressure probe. CONCLUSIONS: Mild nerve compression produces a very
      localized axonal depolarization at the compression site followed by
      hyperpolarization upon release of compression, as expected from focal ischemia.
      SIGNIFICANCE: The current results imply that the sharply-localized conduction
      abnormalities demonstrated electrophysiologically in peripheral nerve entrapment
      syndromes and compression myelopathies may, in part, result from compression
      induced focal nerve ischemia.

PMID- 19101204
TI  - A look at the Journal of Science and Medicine in Sport-Past, present and future.

PMID- 19101205
TI  - Immune barriers to successful gene therapy.
AB  - Immune responses to viral vectors pose one of the main obstacles to successful
      human gene replacement therapy, unless gene transfer vectors are applied to
      immune-privileged sites. Both innate and adaptive immunity work in concert
      against sustained gene transfer, but the functions of patients' regulatory T
      cells (Tregs) and tolerogenic dendritic cells (DCs) could potentially be
      harnessed to reduce these immune responses. Over the last few years,
      immunologists have gained an ever-increasing knowledge of immunoregulatory
      pathways, especially those that prevent or dampen adaptive immune responses. The
      gene therapy community is now in a position to use this expanding knowledge in
      basic immunology to overcome the so far nearly unsurpassable obstacles posed by
      the immune system to the long-term replacement of missing or faulty genes by the
      use of viral vectors. Here, we discuss the current challenges in overcoming
      immune barriers to gene therapy. In addition, we point out potential strategies
      that might allow circumvention of cellular or humoral immune responses against
      the vector or the transgene product.

PMID- 19101206
TI  - Including parasites in food webs.
AB  - Growing evidence indicates parasite inclusion in food-web analyses is a logical
      default. Comparisons of food webs including and excluding host-parasite
      interactions demonstrate the influence of parasites on community dynamics.
      Although including parasites is undoubtedly informative, the necessary level of
      detail exists for only a handful of systems. In a recent Ecology Letters article,
      Lafferty et al. pose many good questions to catalyze discussions for determining
      when and how parasites should be incorporated into food-web analyses.

PMID- 19101207
TI  - The enigmatic asparaginyl endopeptidase of helminth parasites.

PMID- 19101208
TI  - No TRAP, no invasion.
AB  - Host-cell invasion by apicomplexan parasites is a unique process that is powered
      by the gliding motility motor and requires a transmembrane link between the
      parasite cytoskeleton and the host cell. The thrombospondin-related anonymous
      protein (TRAP) from Plasmodium plays such a part during sporozoite invasion by
      linking to actin through its cytoplasmic tail while binding to hepatocytes via
      its extracellular portion. In recent years, there have been major advances in the
      identification and characterization of TRAP-family proteins in the other invasive
      stages of Plasmodium as well as other Apicomplexa. This review summarizes the
      recent experimental data on these TRAP-family proteins, focusing on their
      structure and function.

PMID- 19101209
TI  - Gender differences in patient perceptions of involvement in myocardial infarction
      care.
AB  - BACKGROUND: Gender differences in the clinical presentation, treatment and
      outcomes of myocardial infarction (MI) have been demonstrated. However, few
      studies have examined gender differences in patients' perceptions of involvement
      in MI care, and whether differing levels of involvement might be associated with
      gender differences in treatment and outcome. AIM: To examine possible gender
      differences in MI patients' perceptions of their involvement during
      hospitalization. METHODS: Questionnaire study conducted in 2005-2006 among MI
      patients under the age of 75 at eleven hospitals. Patient ratings of their
      involvement during hospitalization were analyzed for age-stratified gender
      differences. RESULTS: Younger (<70 years of age) female MI patients placed
      significantly more value on shared decision-making than younger (<70) men. More
      than one third of patients would have liked to be more involved in their care
      during hospitalization and discharge planning, with women significantly more
      dissatisfied than men. Significantly fewer younger female patients discussed
      secondary preventive lifestyle changes with cardiology staff prior to hospital
      discharge. CONCLUSION: Significant age-specific gender differences exist in MI
      patient ratings of, and satisfaction with, involvement during hospitalization.
      Further study is needed regarding the possible role of involvement in the
      recognized gender differences in the treatment and outcomes of MI.

PMID- 19101210
TI  - Hyperalgesia in opioid-managed chronic pain and opioid-dependent patients.
AB  - This observational study aimed to determine whether pain sensitivity in patients
      with noncancer chronic pain, taking either methadone or morphine, is similar to
      patients maintained on methadone for dependence therapy, compared with a control
      group. Nociceptive thresholds were measured on a single occasion with von Frey
      hairs, electrical stimulation, and cold pressor tests. In all subjects receiving
      methadone or morphine, nociceptive testing occurred just before a scheduled dose.
      Cold pressor tolerance values in patients with noncancer, chronic pain, treated
      with morphine and methadone, were 18.1 +/- 2.6 seconds (mean +/- SEM) and 19.7 +/
      2.3 seconds, respectively; in methadone-maintained subjects it was 18.9 +/- 1.9
      seconds, with all values being significantly (P < .05) lower than opioid-naive
      subjects (30.7 +/- 3.9 seconds). These results indicate that patients with
      chronic pain managed with opioids and methadone-maintained subjects are
      hyperalgesic when assessed by the cold pressor test but not by the electrical
      stimulation test. None of the groups exhibited allodynia as measured using the
      von Frey hairs. These results add to the growing body of evidence that chronic
      opioid exposure increases sensitivity to some types of pain. They also
      demonstrate that in humans, this hyperalgesia is not associated with allodynia.
      PERSPECTIVE: This article presents an observational study whereby the pain
      sensitivity of patients with chronic pain managed with opioids and opioid
      maintained patients were compared with opioid-naive patients. The results suggest
      that opioid use may contribute to an increase in the sensitivity to certain pain
      experimental stimuli.

PMID- 19101211
TI  - Physical pain and emotional suffering: the case for palliative sedation.

PMID- 19101212
TI  - Diagnostic validity of criteria for sacroiliac joint pain: a systematic review.
AB  - A systematic literature review was conducted to determine the diagnostic validity
      of the criteria for sacroiliac (SI) joint pain as proposed by the International
      Association for the Study of Pain (IASP). Databases were searched up to September
      2007. Quality of the studies was assessed using a Quality Assessment of
      Diagnostic Accuracy Studies (QUADAS) tool. Sensitivity, specificity, and
      diagnostic odds ratios (DOR) were calculated together with 95% confidence
      intervals (CI). Statistical pooling was conducted for results of provocative
      tests. Eighteen studies were included. Five studies examined the pattern of SI
      joint pain, whereas another 5 examined stressing test specific for SI joint pain.
      None of the studies evaluated the diagnostic validity of the SI joint
      infiltration or the diagnostic validity of the IASP criteria set as a whole. In
      all studies, the SI joint selective infiltration was used as a gold standard;
      however, the technique, medications, and required pain relief after the
      infiltration varied considerably between the studies. Taking the double
      infiltration technique as reference test, the pooled data of the thigh thrust
      test (DOR, 18.461; CI, 5.82 to 58.53), compression test (DOR, 3.88; CI, 1.7 to
      8.9), and 3 or more positive stressing tests (DOR, 17.16; CI, 7.6 to 39) showed
      discriminative power for diagnosing SI joint pain. PERSPECTIVE: This review of
      clinical studies focused on the diagnostic validity of the IASP criteria for
      diagnosing SI joint pain. A meta-analysis showed that the thigh thrust test, the
      compression test, and 3 or more positive stressing tests have discriminative
      power for diagnosing SI joint pain. Because a gold standard for SI joint pain
      diagnosis is lacking, the diagnostic validity of tests related to the IASP
      criteria for SI joint pain should be regarded with care.

PMID- 19101213
TI  - Cross-platform Q-TOF validation of global exo-metabolomic analysis: application
      to human glioblastoma cells treated with the standard PI 3-Kinase inhibitor
      LY294002.
AB  - The reproducibility of a metabolomics method has been assessed to identify
      changes in tumour cell metabolites. Tissue culture media extracts were analyzed
      by reverse phase chromatography on a Waters Acquity T3 column with a 13 min 0.1%
      formic acid: acetonitrile gradient on Agilent and Waters LC-Q-TOF instruments.
      Features (m/z, RT) were extracted by MarkerLynx (Waters) and Molecular Feature
      Extractor (Agilent) in positive and negative ionization modes. The number of
      features were similar on both instruments and the reproducibility of ten
      replicates was <35% signal variability for approximately 50% and 40% of all ions
      detected in positive and negative ionization modes, respectively. External
      standards spiked to the matrix showed CVs <25% in peak areas within and between
      days. U87MG glioblastoma cells exposed to the PI 3-Kinase inhibitor LY294002
      showed significant alterations of several confirmed features. These included
      glycerophosphocholine, already shown by NMR to be modulated by LY294002,
      highlighting the power of this technology for biomarker discovery.

PMID- 19101214
TI  - Ring-opening polymerization of epsilon-caprolactone initiated by the antitumor
      agent doxifluridine.
AB  - A novel 5'-deoxy-5-fluorouridine-poly(epsilon-caprolactone) (5'-DFUR-PCL) polymer
      was synthesized from the antitumor agent doxifluridine (5'-DFUR) by the ring
      opening polymerization of epsilon-caprolactone (epsilon-CL) using Sn(II) 2
      ethylhexanoate (Sn(Oct)2) as the catalyst. The structure and molecular weight of
      these polymers were further elucidated by proton nuclear magnetic resonance and
      gel-permeation chromatography. The results revealed that the molecular weights of
      the 5'-DFUR-PCL polymers were close to the theoretical values calculated from the
      epsilon-CL to 5'-DFUR molar ratios and their recovery yields were as high as 90%.
      Two mechanisms of epsilon-CL polymerization initiated by Sn(Oct)2 were proposed
      involving either a single or two 5'-DFUR molecules. This study has provided an
      efficient method for the preparation of 5'-DFUR-PCL polymers. These novel 5'-DFUR
      PCL polymers can be applied as drugs on carriers without the need for the coating
      or grafting processes associated with drugs in drug delivery and have great
      potential for cancer therapy.

PMID- 19101215
TI  - Long-term effects of neonatal hydrocortisone treatment for chronic lung disease
      on the developing brain and heart.
AB  - Despite modern perinatal intensive care techniques, chronic lung disease remains
      a problem in preterm-born infants. The most commonly and almost exclusively
      prescribed drug to treat this disorder is dexamethasone. Corticosteroids improve
      short-term respiratory function; however, many side-effects have been reported
      and the adverse long-term effects of dexamethasone on neurodevelopment are
      particularly alarming. Hydrocortisone could be a suitable alternative for
      dexamethasone, if equally effective with fewer side-effects. This review
      evaluates the current literature on neonatal hydrocortisone treatment for chronic
      lung disease with regards to long-term neurodevelopmental outcome and
      cardiovascular effects. The neurodevelopmental studies do not show any adverse
      effects of hydrocortisone on neurocognitive and motor outcome, nor on incidence
      of brain abnormalities on magnetic resonance imaging or on long-lasting
      programming effects on the hypothalamus-pituitary-adrenal axis. At school age,
      cardiovascular stress response was the same in hydrocortisone-treated children
      compared with a reference group. Hydrocortisone seems a safe alternative to
      dexamethasone, but more double-blind randomised studies are needed.

PMID- 19101216
TI  - High-pressure paint gun injection injury of the hand: a case report.

PMID- 19101217
TI  - Free flaps in nephrotic syndrome patients.

PMID- 19101218
TI  - Nicolo Manuzzi (1639-1717) and the first report of the Indian Rhinoplasty.
AB  - The Venetian adventurer Nicolo Manuzzi composed a detailed manuscript about the
      Moghul Empire late in the 17th century towards the end of his life. It contained
      an accurate description of the Indian Rhinoplasty. Although it was returned to
      Europe from India early in the 18th century it was never published. Had it been
      disseminated amongst the surgeons of the day we can speculate that the 'BL'
      letter to the Gentleman's Magazine in 1794 would not have been such a surgical
      'bombshell' but more a damp squib! This paper records Manuzzi's story which
      finally came to light when his manuscript was translated into English and
      published in 1907. We believe that these details are not well known amongst
      plastic surgeons.

PMID- 19101219
TI  - An evaluation of Midwifery Group Practice. Part I: clinical effectiveness.
AB  - BACKGROUND: Midwifery Group Practice (MGP) is a continuity of midwifery care
      model for women in all risk groups (Low, Moderate and High) available at a
      tertiary metropolitan hospital in Australia. This demonstration study aimed to
      compare the clinical effectiveness of MGP with other models of care at the
      hospital. METHODS: Comparisons of clinical outcomes were made between women who
      received care under MGP (n=618) and those receiving 'Other' modes of care at the
      hospital (n=3548) between three risk categories over a 15-month period. RESULTS:
      There were more Low (MGP n=218, 35.3%, 'Other' n=773, 21.8%) and fewer High Risk
      (MGP n=46, 7.4%, 'Other' n=564, 15.9%) women in MGP, with similar proportions of
      Moderate Risk women (MGP n=354, 57.3%, 'Other' n=2211, 62.3%). Significant
      differences include: fewer assisted deliveries for Moderate Risk women in MGP
      (27.7% MGP, 46.1% 'Other'); fewer labour inductions (Low Risk: 12.8% MGP, 25.1%
      'Other'; Moderate Risk: 21.8% MGP, 29.5% 'Other'; High Risk: 19.6% MGP, 34.9%
      'Other'); less epidural analgesia (Low Risk: 22.5% MGP, 49.0% 'Other'; Moderate
      Risk: 20.3% MGP, 38.4% 'Other'; High Risk: 17.4% MGP, 32.6% 'Other'); and
      differences in the overall pattern of perineal trauma. No significant differences
      were found in the incidence of post-partum haemorrhage, antenatal hospital
      admissions, or neonatal admission to Special or Intensive Care. CONCLUSIONS: MGP
      is clinically effective when practiced in a routine setting.

PMID- 19101220
TI  - Effect of caldaret on the incidence of severe left ventricular dysfunction in
      patients with ST-elevation myocardial infarction undergoing primary coronary
      intervention.
AB  - Primary percutaneous coronary intervention (PCI) decreases myocardial damage in
      patients with ST-elevation myocardial infarction (STEMI). Cellular reperfusion
      injury associated with calcium overload may limit myocardial salvage. We
      previously showed (CASTEMI trial) that caldaret (MCC-135), which modulates
      myocardial calcium handling when administered before PCI in patients with STEMI,
      did not change residual left ventricular (LV) function. The aim of this
      subanalysis was to examine whether caldaret decreases the incidence of LV
      dysfunction (LV ejection fraction <or=30%) in patients with STEMI undergoing
      primary PCI. Of 387 patients enrolled in the CASTEMI study, 239 had single-photon
      emission computed tomographic data on days 7 and 30 after the infarct. The
      incidence of LV dysfunction in patients receiving low- and high-dose caldaret was
      compared with placebo. At day 30 after the infarct, there was a significant
      decrease in the incidence of LV dysfunction in patients receiving low and high
      doses of caldaret versus placebo (8.0%, 6.9% vs 17.5%, p <0.05 for the 2
      comparisons). This difference was more pronounced in patients with anterior wall
      MI and Thrombolysis In Myocardial Infarction grade 0/1 flow. In this group, 52%
      decrease in the incidence of LV dysfunction was observed already on day 7 after
      the infarct (p = 0.026). The incidence of an LV ejection fraction <or=30% was
      significantly decreased between day 7 and day 30 in patients treated with the 2
      doses of caldaret and was unchanged in the placebo group. In conclusion,
      treatment with intravenous caldaret in patients with STEMI undergoing primary PCI
      is associated with a significant decrease in the incidence of severe LV
      dysfunction.

PMID- 19101222
TI  - Frequency of coronary artery bypass grafting following implantation of a
      paclitaxel-eluting or a bare-metal stent into a single coronary artery.
AB  - Limited data are available on the relative effect of drug-eluting versus bare
      metal stents on the requirement for subsequent coronary artery bypass grafting
      (CABG). The aim of this study was to evaluate the incidence and predictors of
      CABG after bare-metal and paclitaxel-eluting coronary stent implantation. A
      patient-level, pooled analysis was conducted of 2,736 patients from 3 double
      blind, randomized trials comparing the slow-release paclitaxel-eluting Taxus
      stent with an otherwise identical bare-metal stent control in single de novo
      coronary lesions, with 5-year follow-up. The rate of target lesion
      revascularization by CABG (TLR-CABG) was reduced from 4.1% in patients with bare
      metal stents to 1.4% in those with Taxus stents (p <0.001). The use of the Taxus
      stent was the strongest predictor of freedom from TLR-CABG on multivariate
      analysis (hazard ratio 0.33, p <0.001). Significant reductions in TLR-CABG with
      Taxus compared with bare-metal stents were seen in the treatment of left anterior
      descending artery lesions (6.1% vs 1.8%, p <0.001) and non-left anterior
      descending artery lesions (2.8% vs 1.3%, p = 0.037), in patients with diabetes
      (6.0% vs 1.0%, p <0.01), and in those without diabetes (3.5% vs 1.6%, p <0.01).
      In conclusion, referral to CABG is significantly less common after stenting
      single coronary lesions with Taxus compared with bare-metal stents. The relative
      reductions in TLR-CABG of 54% in patients without diabetes, 87% in patients with
      diabetes, 70% in left anterior descending artery lesions, and 54% in non-left
      anterior descending artery lesions with Taxus compared with bare-metal stents
      should be considered during stent selection.

PMID- 19101221
TI  - Tailored clopidogrel loading dose according to platelet reactivity monitoring to
      prevent acute and subacute stent thrombosis.
AB  - Stent thrombosis remains a significant pitfall of percutaneous coronary
      intervention (PCI). A recent trial observed that an adjusted loading dose (LD) of
      clopidogrel according to platelet monitoring decreases the rate of major adverse
      cardiovascular events after PCI. We investigated if such a strategy of a tailored
      clopidogrel LD according to platelet reactivity monitoring could decrease the
      rate of stent thrombosis. This multicenter prospective randomized study included
      429 patients with a low clopidogrel response after a 600-mg LD undergoing PCI.
      Patients were randomized to a control group (n = 214) and to a vasodilator
      stimulated phosphoprotein (VASP)-guided group (n = 215). In the VASP-guided
      group, patients received up to 3 additional 600-mg LDs of clopidogrel to obtain a
      VASP index <50% before PCI. The primary end point was the rate of stent
      thrombosis at 1 month. Secondary end points were rates of major adverse
      cardiovascular events and bleeding. Patients in the 2 groups had a high body mass
      index and were often diabetic (control vs VASP-guided group 28 +/- 5.1 vs 27.9 +/
      4.7 kg/m(2), p = 0.8, and 39% vs 33%, p = 0.2, respectively). PCI was performed
      in most patients for acute coronary syndrome in the 2 groups (52.3% vs 50.7%, p =
      0.8). Despite a 2,400-mg LD of clopidogrel, 8% of patients in the VASP-guided
      group remained low responders. The rate of stent thrombosis was significantly
      lower in the VASP-guided group (0.5% vs 4.2%, p <0.01). The rate of major adverse
      cardiovascular events was also higher in the control group (8.9% vs 0.5%, p
      <0.001). There was no difference in the rate of bleeding (2.8% vs 3.7%, p = 0.8).
      In conclusion, a tailored clopidogrel LD according to platelet reactivity
      monitoring decreases the rate of early stent thrombosis after PCI without
      increasing bleeding.

PMID- 19101223
TI  - Usefulness of left ventricular diastolic dysfunction as a predictor of one-year
      rehospitalization in survivors of acute myocardial infarction.
AB  - Presence of severe left ventricular (LV) diastolic function has been shown to
      independently predict risk of heart failure or death after acute myocardial
      infarction (AMI). We aimed to determine whether common echocardiographic
      parameters and (LV) diastolic function evaluated during AMI hospitalization can
      predict the risk of rehospitalization, up to 1 year after AMI. One hundred ninety
      consecutive patients with AMI, who were prospectively enrolled in a longitudinal
      post-AMI registry, had survived for 1 year, and had a clinically indicated
      echocardiogram during the index admission, were included in the study. The
      independent effect of diastolic dysfunction on 1-year all-cause rehospitalization
      was assessed using multivariable proportional hazards regression. Average age was
      62.5 years, 93% were Caucasian, 66% were men, and mean LV ejection fraction was
      46%. At 1 year, 78 patients (41%) had been rehospitalized >or=1 time. In
      multivariable analysis, presence of severe LV diastolic dysfunction was the only
      echocardiographic variable that predicted increased risk of rehospitalization 1
      year after AMI (hazard ration 3.31, 95% confidence interval 1.26 to 8.69).
      Seventy-eight percent of patients with severe LV diastolic dysfunction
      (restrictive diastolic physiology) compared with 30% with normal diastolic
      function (p = 0.0052) and 37% with nonrestrictive physiology during the index
      admission were rehospitalized. In conclusion, severe LV diastolic dysfunction is
      the only echocardiographic predictor of rehospitalization in survivors of AMI and
      routine assessment of diastolic function during AMI hospitalization can provide
      additional prognostic risk stratification at dismissal.

PMID- 19101224
TI  - Prognostic value of a multimarker approach for patients presenting to hospital
      with acute chest pain.
AB  - To evaluate the prognostic role of novel biomarkers for the risk stratification
      of patients admitted with ischemic-type chest pain, a prospective study of 664
      patients presenting to 2 coronary care units with ischemic-type chest pain was
      conducted over 3 years beginning in 2003. Patients were assessed on admission for
      clinical characteristics, electrocardiographic findings, renal function, cardiac
      troponin T (cTnT), markers of myocyte injury (heart fatty acid-binding protein [H
      FABP] and glycogen phosphorylase BB), neurohormonal activation (N-terminal-pro
      brain natriuretic peptide [NT-pro-BNP]), hemostatic activity (fibrinogen and D
      dimer), and vascular inflammation (high-sensitivity C-reactive protein,
      myeloperoxidase, matrix metalloproteinase-9, pregnancy-associated plasma protein
      A, and soluble CD40 ligand). A >or=12-hour cTnT sample was also obtained.
      Myocardial infarction (MI) was defined as peak cTnT >or=0.03 microg/L. Patients
      were followed for 1 year from the time of admission. The primary end point was
      death or MI. Elevated fibrinogen, D-dimer, H-FABP, NT-pro-BNP, and peak cTnT were
      predictive of death or MI within 1 year (unadjusted odds ratios 2.5, 3.1, 5.4,
      5.4, and 6.9, respectively). On multivariate analysis, H-FABP and NT-pro-BNP were
      selected, in addition to age, peak cTnT, and left ventricular hypertrophy on
      initial electrocardiography, as significant independent predictors of death or MI
      within 1 year. Patients without elevations of H-FABP, NT-pro-BNP, or peak cTnT
      formed a very low risk group in terms of death or MI within 1 year. A very high
      risk group had elevations of all 3 biomarkers. In conclusion, the measurement of
      H-FABP and NT-pro-BNP at the time of hospital admission for patients with
      ischemic-type chest pain adds useful prognostic information to that provided by
      the measurement of baseline and 12-hour cTnT.

PMID- 19101225
TI  - Temporal course of pregnancy-associated plasma protein-A in angioplasty-treated
      ST-elevation myocardial infarction patients and potential significance of
      concomitant heparin administration.
AB  - Pregnancy-associated plasma protein-A (PAPP-A) is a putative plaque instability
      marker. In acute coronary syndromes, the disrupted culprit plaque contains
      abundant PAPP-A, and circulating PAPP-A levels predict clinical outcomes.
      Determinants of circulating PAPP-A levels, however, are not fully understood, and
      the potential role of concomitant heparin administration has not previously been
      evaluated. The purposes of the present study were to evaluate in-hospital levels
      of PAPP-A compared with other circulating biomarkers in patients with acute
      myocardial infarctions and to explore the potential impact of concomitant heparin
      administration on PAPP-A levels in an animal experiment. Group A comprised 84
      patients with ST elevation myocardial infarctions (STEMIs) who were treated with
      heparin and transferred for primary percutaneous coronary intervention. Plasma
      samples were obtained at the time of primary percutaneous coronary intervention,
      twice within the next 24 hours, and subsequently daily during hospitalization.
      Levels of PAPP-A, troponin T, soluble cluster of differentiation 163, N-terminal
      pro-brain natriuretic peptide, and high-sensitivity C-reactive protein were
      determined. PAPP-A levels were also determined in 2 historical cohorts not given
      heparin: 14 patients with STEMIs (group B) and 56 patients with non-ST elevation
      myocardial infarctions (group C). The impact of concomitant heparin
      administration on the clearance of PAPP-A from the circulation was also explored
      in mice. In group A, PAPP-A levels were increased in the initial plasma sample in
      95% of patients presenting within 3 hours of symptom onset, whereas increased
      levels of troponin T, soluble cluster of differentiation 163, N-terminal-pro
      brain natriuretic peptide, and high-sensitivity C-reactive protein were
      detectable in 45%, 15%, 50%, and 35% of patients, respectively. Compared with
      group A, lower levels of PAPP-A were observed in the initial plasma samples drawn
      in groups B (p = 0.07) and C (p <0.001) not given heparin. In the animal
      experiment, concomitant heparin administration resulted in increased levels of
      PAPP-A and delayed clearance of PAPP-A from the circulation. In conclusion, PAPP
      A is markedly elevated in the earliest hours after the onset of symptoms in
      patients with STEMIs treated with heparin and primary percutaneous coronary
      intervention, and in animal studies, heparin administration is associated with a
      significant increase in PAPP-A levels, presumably because of the detachment of
      PAPP-A from the vessel wall. If future studies confirm that concomitant heparin
      administration also increases PAPP-A levels in humans, the prognostic role of
      PAPP-A in patients with STEMIs needs to be reevaluated.

PMID- 19101226
TI  - Effectiveness of atrial fibrillation as an independent predictor of death and
      coronary events in patients having coronary angiography.
AB  - The impact of atrial fibrillation (AF) on future coronary events is uncertain. In
      particular, the prognostic impact of AF in the clinically important population of
      coronary patients who undergo angiography is unknown. The aim of this study was
      to investigate (1) the prevalence of AF, (2) its association with coronary
      atherosclerosis, and (3) its impact on future coronary events in patients who
      undergo angiography. Electrocardiograms were evaluated in a consecutive series of
      613 patients who underwent coronary angiography. Prospectively, death and
      cardiovascular events were recorded over 4.0 +/- 0.6 years. Among these patients,
      37 (6%) at baseline had AF, and 576 (94%) were in sinus rhythm. The presence of
      AF was associated with a lower prevalence of coronary artery disease and of
      coronary diameter narrowing >or=50% on baseline angiography. However,
      prospectively, patients with AF were at a strongly increased risk for all-cause
      mortality (adjusted hazard ratio 5.15, 95% confidence interval 2.36 to 11.26, p
      <0.001), coronary death (hazard ratio 8.16, 95% confidence interval 2.89 to
      23.09, p <0.001), and major coronary events (hazard ratio 3.80, 95% confidence
      interval 1.45 to 9.94, p = 0.007). In conclusion, although inversely associated
      with the presence of angiographically determined coronary atherosclerosis, AF is
      a strong predictor of death and future coronary events in patients with coronary
      artery disease who undergo coronary angiography.

PMID- 19101227
TI  - Relation of clinical benefit of raising high-density lipoprotein cholesterol to
      serum levels of low-density lipoprotein cholesterol in patients with coronary
      heart disease (from the Bezafibrate Infarction Prevention Trial).
AB  - Low high-density lipoprotein (HDL) cholesterol is a strong independent predictor
      of cardiovascular risk. The present study was designed to assess the relation
      between the clinical response to HDL cholesterol modification and serum levels of
      low-density lipoprotein (LDL) cholesterol in patients with coronary artery
      disease (CAD). The risk for a major cardiac event (defined as nonfatal myocardial
      infarction or cardiac death) during a median 7.9-year follow-up period in 3,020
      patients with CAD enrolled in the Bezafibrate Infarction Prevention (BIP) trial
      was related to changes in lipid levels during the study. Baseline LDL cholesterol
      levels were categorized according to National Cholesterol Education Program Adult
      Treatment Panel III criteria. Multivariate analysis demonstrated that the benefit
      of HDL cholesterol increase was most pronounced in patients with low baseline LDL
      cholesterol (<or=129 mg/dl; 29% risk reduction per 5 mg/dl increment in HDL
      cholesterol, p = 0.02), intermediate in patients with intermediate LDL
      cholesterol (130 to 159 mg/dl; 13% risk reduction per 5 mg/dl increment in HDL
      cholesterol, p = 0.03), and nonsignificant in patients with high LDL cholesterol
      (>or=160 mg/dl; hazard ratio 0.94, 95% confidence interval 0.75 to 1.17, p =
      0.14). A similar relation was shown for risk reduction-associated triglyceride
      decrements, whereas the benefit of LDL cholesterol reduction was more pronounced
      in patients with baseline LDL cholesterol >or=130 mg/dl. In conclusion, these
      data suggest that the clinical response to HDL cholesterol and triglyceride
      modification is inversely related to baseline LDL cholesterol levels. Thus,
      combined assessment of baseline and follow-up lipid levels to direct therapeutic
      goals in patients with CAD may provide incremental prognostic information to
      secondary prevention that is based solely on LDL cholesterol modification.

PMID- 19101229
TI  - Relation of plaque characteristics defined by coronary computed tomographic
      angiography to ST-segment depression and impaired functional capacity during
      exercise treadmill testing in patients suspected of having coronary heart
      disease.
AB  - Sixty-four-detector-row coronary computed tomographic angiography (CCTA) has been
      proposed for the evaluation of low- to intermediate-risk patients with suspected
      coronary artery disease (CAD). Historically, exercise treadmill testing (ETT)
      measures of ST-segment depression (STD) and the Duke treadmill score (DTS) have
      been used to evaluate myocardial ischemia and functional capacity. The relation
      of plaque characteristics on CCTA to STD and DTS is unknown. In this study, 156
      low- to intermediate-risk patients without known CAD who underwent ETT and CCTA
      were evaluated. By ETT, 22% (n = 35) had STD and 27% (n = 42) had abnormal DTS.
      On CCTA, 21% (n = 33) had obstructive CAD (>or=70% stenosis) and 49% (n = 77) had
      nonobstructive CAD (<70% stenosis). Forty-six percent of patients (n = 16) with
      and 15% (n = 15) without STD had obstructive CAD. After multivariate adjustment,
      only age and obstructive CAD on CCTA predicted STD (odds ratio [OR] 1.59, 95%
      confidence interval [CI] 1.08 to 2.34 per decade, and OR 3.38, 95% CI 1.32 to
      8.64, respectively) and abnormal DTS (OR 1.61, 95% CI 1.14 to 2.28, and OR 4.67,
      95% CI 1.97 to 11.03, respectively). After adjustment for age, more coronary
      segments with mixed plaque, in contrast to calcified or noncalcified plaque,
      predicted STD (OR 1.48, 95% CI 1.18 to 1.85) and abnormal DTS (OR 1.30, 95% CI
      1.05 to 1.61). In conclusion, measures of plaque on CCTA identify patients more
      likely to have STD and higher risk DTS, while providing incremental diagnostic
      yield for the detection of obstructive CAD beyond ETT.

PMID- 19101228
TI  - Relation of serum fetuin-A levels to coronary artery calcium in African-American
      patients on chronic hemodialysis.
AB  - Vascular calcium deposition in end-stage renal disease occurs commonly, but its
      relation to cardiovascular risk factors and fetuin-A levels in African Americans
      is not known. Compliant African American patients who were undergoing
      hemodialysis (HD; n = 17) agreed to undergo 64-slice multidetector computed
      tomography for the assessment of coronary artery calcium score (CACS). The
      relation between traditional cardiovascular risk factors (i.e., age; gender;
      dialysis vintage; history of diabetes; means of the previous 3 years of weekly
      predialysis blood pressure values and hemoglobin levels; means of monthly values
      of calcium, phosphorus, alkaline phosphatase, uric acid; and albumin; and means
      of quarterly measurements of parathyroid hormone and lipids) and fetuin-A levels
      and CACS was explored using univariate analyses. Serum phosphorus levels over the
      previous 3 years were well controlled. The CACS range was 0 to 3,877 Agatston
      units (mean 996, median 196). Among the tested variables, only fetuin-A was
      significantly and inversely associated with CACS (standardized beta = -0.64, 95%
      confidence interval -18.09 to -3.62, p = 0.006). There was no association between
      age and fetuin-A level (standardized beta = -0.02, 95% confidence interval -0.10
      to 0.23). In conclusion, African-American patients who were undergoing long-term
      hemodialysis and with good phosphorus control exhibited a strong inverse
      correlation between fetuin-A level and CACS that was independent of age.

PMID- 19101230
TI  - Arterial age as a function of coronary artery calcium (from the Multi-Ethnic
      Study of Atherosclerosis [MESA]).
AB  - It has been proposed that coronary artery calcium (CAC) can be used to estimate
      arterial age in adults. Supporting this concept is that chronologic age, as used
      in cardiovascular risk assessment, is a surrogate for atherosclerotic burden.
      This measure can provide patients with a more understandable version of their CAC
      scores (e.g., "You are 55 years old, but your arteries are more consistent with
      an arterial age of 65 years"). The aim of this study was to describe a method of
      calculating arterial age by equating estimated coronary heart disease (CHD) risk
      for observed age and CAC. Arterial age is then the risk equivalent of CAC. Data
      from the Multi-Ethnic Study of Atherosclerosis (MESA), a cohort study of 6,814
      participants free of clinical cardiovascular disease and followed for an average
      of 4 years, were used. Estimated arterial age was obtained as a simple linear
      function of log-transformed CAC. In a model for incident CHD risk controlling for
      age and arterial age, only arterial age was significant, indicating that observed
      age does not provide additional information after controlling for arterial age.
      Framingham risk calculated using this arterial age was more predictive of short
      term incident coronary events than Framingham risk on the basis of observed age
      (area under the receiver-operating characteristic curve 0.75 for Framingham risk
      on the basis of observed age and 0.79 using arterial age, p = 0.006). In
      conclusion, arterial age provides a convenient transformation of CAC from
      Agatston units to a scale more easily appreciated by patients and treating
      physicians.

PMID- 19101231
TI  - Relation of corneal arcus to cardiovascular disease (from the Framingham Heart
      Study data set).
AB  - Corneal arcus is a lipid-rich deposit at the corneoscleral limbus that shares
      some similarities with the lipid deposition of atherosclerosis. Epidemiologic
      studies examining the association between corneal arcus and coronary artery
      disease (CAD) have yielded mixed results. This study was conducted to determine
      if corneal arcus is an independent risk factor for cardiovascular disease (CVD)
      and CAD. A prospective analysis was performed using Cox proportional-hazards
      regression models in the Framingham Heart Study Original Cohort and Offspring
      Cohort database. This cohort included 23,376 patient-examinations, during 3,890
      (17%) of which corneal arcus was identified. Corneal arcus was a predictor of CVD
      and CAD at 4 years (hazard ratios [HRs] 2.28 and 1.99, respectively) and 8 years
      (HRs 2.52 and 2.35, respectively) of follow-up (p <0.0001 for all). Corneal arcus
      was no longer predictive of either CVD or CAD, however, after adjustment for age
      and gender at 4 years (HRs 1.07 and 1.01, respectively) and 8 years (HRs 1.18 and
      1.17, respectively) of follow-up (p >0.05 for all). In conclusion, corneal arcus
      predicted CVD and CAD in the community-based Framingham Heart Study cohort
      because of the strong association of corneal arcus with increasing age. To date,
      this is the largest and lengthiest population-based cohort study examining the
      direct association between corneal arcus and CVD and CAD.

PMID- 19101232
TI  - Comparison of outcome in catheter ablation of atrial fibrillation in patients
      with versus without the metabolic syndrome.
AB  - Previous studies have reported that metabolic syndrome (MS) is associated with
      the development of atrial fibrillation (AF). However, its impact on the atrial
      substrate properties and catheter ablation in patients with AF is still unclear.
      This study consisted of 282 patients with AF (216 with paroxysmal AF and 66 with
      nonparoxysmal AF) who underwent catheter ablation using a 3-dimensional mapping
      system (NavX). Detailed AF mapping (frequency analysis and complex fractionated
      electrographic mapping) was performed in 59 patients. The patients were
      classified on the basis of MS, which was defined according to the guidelines of
      the National Cholesterol Education Program Adult Treatment Panel III. Patients
      with MS had larger left atrial sizes, shorter fractionated intervals, and higher
      dominant frequencies compared with those without it. Higher incidences of complex
      fractionated atrial electrographic sites located in the left atrial appendage
      base, coronary sinus, and crista terminalis regions were found in patients with
      MS. Patients with MS had a higher incidence of recurrent AF compared with those
      without MS (55% vs 24%, p <0.001). A higher incidence of recurrent AF from non
      pulmonary vein origins was observed in patients with MS compared with those
      without it (45% vs 20%, p = 0.037). In conclusion, MS is associated with larger
      left atrial size and an arrhythmogenic substrate, which may increase the risk for
      recurrence after the ablation of AF. Close follow-up with good control of any
      metabolic disturbances may be needed in patients with MS to improve their
      outcomes after AF ablation.

PMID- 19101233
TI  - Clinical and prognostic value of Duke's Activity Status Index along with plasma B
      type natriuretic peptide levels in chronic heart failure secondary to ischemic or
      idiopathic dilated cardiomyopathy.
AB  - The Duke Activity Status Index (DASI) provides an accurate estimate of functional
      capacity in patients with chronic heart failure (HF). The aim of this study was
      to evaluate the prognostic value of the DASI against well-established prognostic
      factors in 130 consecutive patients hospitalized for worsening HF symptoms (mean
      age 64 +/- 12 years, mean left ventricular ejection fraction 26 +/- 7%), followed
      for 9 months for major cardiovascular events, defined as death or hospitalization
      for HF decompensation. During follow-up, 77 of 130 patients (59%) experienced
      major cardiovascular events after a median time of 60 days (range 5 to 220).
      Patients with eventful courses were in higher New York Heart Association
      functional classes (p = 0.001) and had shorter 6-minute walking distances (p =
      0.041), lower ejection fractions (p <0.001), higher plasma B-type natriuretic
      peptide (BNP) levels at hospital admission and discharge (both p <0.001), and
      lower DASI scores (16 +/- 12 vs 25 +/- 17, p = 0.003). In multivariate Cox
      regression analysis including all these variables, only BNP level at discharge (p
      = 0.006) and DASI score (p = 0.047) were independently associated with event-free
      survival. A BNP cutoff of 697 pg/ml predicted future events with 59% sensitivity
      and 86% specificity, while a DASI score cutoff of 8 had 76% sensitivity and 25%
      specificity. The combination of the 2 cutoffs predicted events with 33%
      sensitivity and 95% specificity. Event-free survival was significantly lower in
      patients with the 2 markers positive (BNP >697 pg/ml and DASI score <8) compared
      with those with with 2 markers negative (63 +/- 27 vs 183 +/- 15 days, log-rank p
      <0.0001). In conclusion, functional status assessment by the DASI bears
      prognostic value, and its combination with plasma BNP may provide quite specific
      risk stratification in patients with chronic HF.

PMID- 19101234
TI  - Association of weight change with subsequent outcomes in patients hospitalized
      with acute decompensated heart failure.
AB  - The association of weight loss achieved through various decongestive strategies
      with clinical outcomes in patients with acute decompensated heart failure (HF) is
      not well described. The aim of this study was to determine the relation between
      weight change during hospitalization and subsequent clinical events in patients
      with decompensated HF. Data from 433 patients hospitalized with advanced HF
      enrolled in the Evaluation Study of Congestive Heart Failure and Pulmonary Artery
      Catheterization Effectiveness (ESCAPE) trial were evaluated. The influence of
      change in weight during hospitalization to clinical outcomes (days alive out of
      the hospital in the first 6 months; death; death or rehospitalization; and death,
      rehospitalization, or cardiac transplantation) was evaluated. On average,
      patients lost approximately 3.6 kg during hospitalization. When categorized into
      3 weight loss tertiles, those in the highest tertile were more likely to be
      older, women, and smokers, with higher body weights, previous percutaneous
      coronary interventions, baseline heart rates, and brain natriuretic peptide and
      blood urea nitrogen values but lower ejection fractions and peak oxygen
      consumption. No significant differences were observed between weight change and
      any in-hospital or follow-up events (days well: hazard ratio 0.995, 95%
      confidence interval 0.975 to 1.016; 180-day death: hazard ratio 1.012, 95%
      confidence interval 0.969 to 1.057; death or rehospitalization at 180 days:
      hazard ratio 1.014, 95% confidence interval 0.990 to 1.038). In conclusion,
      weight loss in patients with acute decompensated HF during hospitalization was
      not related to clinical end points. These data challenge the merit of using
      weight as a surrogate end point for more important clinical events (i.e., death
      and/or rehospitalization) in patients with HF in the design of treatment
      strategies for novel therapeutic agents in randomized controlled clinical trials.

PMID- 19101235
TI  - Effectiveness of digoxin in reducing one-year mortality in chronic heart failure
      in the Digitalis Investigation Group trial.
AB  - Post hoc analyses of the Digitalis Investigation Group (DIG) trial indicate that
      digoxin at low (0.5 to 0.9 ng/ml) serum digoxin concentration (SDC) reduces
      mortality, which is eliminated at higher (>or=1 ng/ml) SDC, and that low-dose
      digoxin (<or=0.125 mg/day) predicts low SDC. In the DIG trial, patients with
      ambulatory chronic systolic and diastolic heart failure (HF) (n = 7,788) in
      normal sinus rhythm receiving angiotensin-converting enzyme inhibitors and
      diuretics were randomized to receive placebo (n = 3,899) or digoxin (n = 3,889).
      The median dose of digoxin (0.25 mg/day) and the target SDC (0.8 to 2.5 ng/ml)
      were higher than what are currently recommended, which in part may explain the
      lack of long-term mortality benefit of digoxin in the DIG trial. To test this
      hypothesis, we examined the effect of digoxin on short-term outcomes; 1-year all
      cause mortality occurred in 392 and 448 patients respectively in the digoxin and
      placebo groups (hazard ratio for digoxin 0.87, 95% confidence interval [CI] 0.76
      to 0.995, p = 0.043). Respective hazard ratios for cardiovascular and HF deaths
      were 0.87 (95% CI 0.76 to 1.01, p = 0.072) and 0.66 (95% CI 0.52 to 0.85, p =
      0.001). All-cause hospitalization occurred in 1,411 and 1,529 patients receiving
      digoxin and placebo respectively (hazard ratio 0.89, 95% CI 0.83 to 0.96, p =
      0.002). Respective hazard ratios for cardiovascular and HF hospitalizations were
      0.82 (95% CI 0.75 to 0.89, p <0.0001) and 0.59 (95% CI 0.52 to 0.66, p <0.0001).
      In conclusion, digoxin reduced 1-year mortality and hospitalization in patients
      with chronic HF receiving angiotensin-converting enzyme inhibitors and diuretics.
      Randomized clinical trials are needed to determine the effect of low-dose digoxin
      in contemporary patients with chronic HF.

PMID- 19101236
TI  - Multimorbidity due to diabetes mellitus and chronic kidney disease and outcomes
      in chronic heart failure.
AB  - Diabetes mellitus (DM) and chronic kidney disease (CKD) are common in patients
      with chronic heart failure (HF) and are associated with poor outcomes. However,
      the impact of multimorbidity due to DM and CKD on outcomes, relative to co
      morbidity due to DM alone, has not been well studied in these patients. Of the
      7,788 patients with chronic HF in the Digitalis Investigation Group trial, 2,218
      had DM. We categorized these patients into those with DM alone (DM-only n =
      1,123) and those with both DM and CKD (DM-CKD n = 1,095). Propensity scores for
      DM-CKD, calculated for each of the 2,218 patients, were used to match 699 pairs
      of patients with DM-only or DM-CKD. Matched Cox regression models were used to
      estimate associations between DM-CKD and outcomes. All-cause mortality occurred
      in 44% (rate 1,648/10,000 person-years) of patients with DM-CKD and 39% (rate
      1,349/10,000 person-years of follow-up) of patients with DM-only (hazard ratio
      when DM-CKD was compared with DM-only 1.34, 95% confidence interval [CI] 1.11 to
      1.62, p = 0.003). All-cause hospitalization occurred in 76% (rate 5,799/10,000
      person-years) and 73% (rate 4,909/10,000 person-years) of patients with DM-CKD
      and DM-only, respectively (hazard ratio 1.16, 95% CI 0.99 to 1.36, p = 0.064).
      Respective hazard ratios for other outcomes were cardiovascular mortality 1.33
      (95% CI 1.07 to 1.66, p = 0.010), HF mortality 1.41 (95% CI 1.02 to 1.96, p =
      0.040), cardiovascular hospitalization 1.17 (95% CI 0.99 to 1.39, p = 0.064), and
      HF hospitalization 1.26 (95% CI 1.03 to 1.55, p = 0.026). In conclusion, compared
      with co-morbidity due to DM alone, the presence of multimorbidity due to DM and
      CKD was associated with increased mortality and morbidity in patients with
      chronic HF.

PMID- 19101237
TI  - Medium term effects of different dosage of diuretic, sodium, and fluid
      administration on neurohormonal and clinical outcome in patients with recently
      compensated heart failure.
AB  - Studies have shown that patients with compensated heart failure (HF) receiving
      high diuretic doses associated with normal sodium diet and fluid intake
      restrictions demonstrated significant reductions in readmissions and mortality
      compared with those who received low-sodium diets, and over a 6-month observation
      period, a reduction in neurohormonal activation was also observed. The aim of
      this study was to evaluate the effects of different sodium diets associated with
      different diuretic doses and different levels of fluid intake on hospital
      readmissions and neurohormonal changes after 6-month follow-up in patients with
      compensated HF. Four hundred ten consecutive patients with compensated HF (New
      York Heart Association class II to IV) aged 53 to 86 years, with ejection
      fractions <35% and serum creatinine <2 mg/dl, were randomized into 8 groups:
      group A (n = 52): 1,000 ml/day of fluid intake, 120 mmol/day, and 250 mg
      furosemide twice daily; group B (n = 51): 1,000 ml/day of fluid intake, 120
      mmol/day, and 125 mg furosemide twice daily; group C (n = 51): 1,000 ml/day fluid
      intake, 80 mmol/day, and 250 mg furosemide twice daily; group D (n = 51): 1,000
      ml/day fluid intake, 80 mmol/day, and 125 mg furosemide twice daily; group E (n =
      52): 2,000 ml/day fluid intake, 120 mmol/day, and 250 mg furosemide twice daily;
      group F (n = 50): 2,000 ml/day fluid intake, 120 mmol/day, and 125 mg furosemide
      twice daily; group G (n = 52): 2,000 ml/day fluid intake, 80 mmol/day, and 250 mg
      furosemide twice daily; and group H (n = 51): 2,000 ml/day fluid intake, 80
      mmol/day, and 125 mg furosemide twice daily. All patients received the treatments
      >or=30 days after discharge and for 180 days afterward. Signs of HF, body weight,
      blood pressure, heart rate, laboratory parameters, electrocardiograms,
      echocardiograms, brain natriuretic peptide, aldosterone, and plasma renin
      activity were examined at baseline and 180 days later. Group A showed the best
      results, with a significant reduction (p <0.001) in readmissions, brain
      natriuretic peptide, aldosterone, and plasma renin activity compared with the
      other groups during follow-up (p <0.001). In conclusion, these data suggest that
      the combination of a normal-sodium diet with high diuretic doses and fluid intake
      restriction, compared with different combinations of sodium diets with more
      modest fluid intake restrictions and conventional diuretic doses, leads to
      reductions in readmissions, neurohormonal activation, and renal dysfunction.

PMID- 19101239
TI  - Cardiac transplantation for cardiac sarcoidosis with initial diagnosis by
      examination of the left ventricular apical "core" excised for insertion of a left
      ventricular assist device for severe chronic heart failure.
AB  - Three quinquagenarians who underwent insertion of a left ventricular assist
      device (LVAD) because of severe heart failure and for whom histologic examination
      of the left ventricular apical "core" (removed to insert the device) showed
      noncaseating giant cell granulomas typical of sarcoidosis are described. Later,
      cardiac transplantation showed widespread sarcoid granulomas in the walls of the
      right and left ventricles and ventricular septum in 2 patients and extensive
      scarring in the third patient in the absence of coronary narrowing. Previously,
      11 patients who underwent cardiac transplantation because of cardiac sarcoidosis
      had been reported, and in 1 of these patients, diagnosis was also initially made
      by examination of the left ventricular core excised at the time of insertion of
      an LVAD. In conclusion, excision of a portion of left ventricular wall to enable
      insertion of a therapeutic device (LVAD) can also serve as the means of
      definitive diagnosis of the underlying cardiac condition.

PMID- 19101238
TI  - Implication of QRS prolongation and its relation to mechanical dyssynchrony in
      idiopathic dilated cardiomyopathy in childhood.
AB  - We explored the role of QRS prolongation (>or=120 ms) and its relation to
      mechanical dyssynchrony and outcomes in childhood idiopathic dilated
      cardiomyopathy (IDC). A total of 89 patients <or=18 years old diagnosed as having
      IDC (21 days to 26 years of follow-up) were investigated. In 20 survivors with
      residual left ventricular (LV) dysfunction, mechanical (interventricular and
      intra-LV) dyssynchrony was assessed. The SD of time from the beginning of QRS
      prolongation to peak systolic contraction was measured in 12 LV segments by
      tissue Doppler imaging. A cut-off value >32.6 ms was used to define intra-LV
      dyssynchrony. The 1- and 5-year survivals were 70% and 53%, respectively.
      Requirement of intravenous inotropes at follow-up (hazard ratio 3.10) and initial
      LV ejection fraction (hazard ratio 0.95) were major prognostic factors. QRS
      prolongation, primarily left bundle branch block, was identified in 16 patients
      (18%) and tended to increase the risk of requiring inotropes. Moreover, none of
      those with QRS prolongation regained normal cardiac function at follow-up. Two
      patients with QRS prolongation showed marked improvement in cardiac function
      after cardiac resynchronization therapy. Mechanical dyssynchrony was noted in all
      patients with QRS prolongation and in 8% (interventricular) or 38% (intra-LV) of
      those without. In conclusion, QRS prolongation was common in childhood IDC and
      was possibly associated with persistent LV dysfunction and worse cardiac outcome.
      Mechanical (inter- and intraventricular) dyssynchrony was highly prevalent in
      those with QRS prolongation and was still often observed in those without.

PMID- 19101240
TI  - Relation of serum ferritin level to cardiovascular fitness among young men.
AB  - Although iron overload is associated with fatigue and low ferritin is associated
      with decreased cardiovascular fitness (CVF), little research has focused on the
      relation of elevated ferritin with CVF in young adult men. An analysis of the
      National Health and Nutrition Examination Survey 1999-2002 was conducted to
      examine the relation between elevated ferritin and CVF in relatively healthy
      young adult men. Adult men aged 20 to 49 years (unweighted n = 1,030, weighted n
      = 28,514,823) who participated in a treadmill test for CVF were evaluated.
      Logistic regressions were computed for ferritin with CVF, adjusting for age, race
      or ethnicity, body mass index, anemia, smoking, exercise, blood donation, and C
      reactive protein. Subjects with ferritin >300 ng/ml were less likely than those
      with normal ferritin to have high CVF (odds ratio [OR] 0.57, 95% confidence
      interval [CI] 0.32 to 0.99). When ferritin was split into categories, in a fully
      adjusted model with a reference group of ferritin at 16 to 100 ng/ml, except for
      ferritin >100 but <150 ng/ml (OR 0.84, 95% CI 0.65 to 1.08), higher ferritin was
      associated with a decreased likelihood of high CVF (>150 but <200 ng/ml: OR 0.55,
      95% CI 0.40 to 0.77; >200 but <300 ng/ml: OR 0.49, 95% CI 0.33 to 0.72; >300
      ng/ml: OR 0.40, 95% CI 0.23 to 0.70). The prevalence of ferritin >150 ng/ml was
      45.5% in young adult men. In conclusion, elevated ferritin levels, even those
      much lower than what is normally considered to be elevated, were associated with
      a decreased likelihood of having high CVF in young adult men.

PMID- 19101241
TI  - Changes in right ventricular pressures between hemodialysis sessions recorded by
      an implantable hemodynamic monitor.
AB  - Intermittent and chronic volume overload might contribute to the onset and
      progression of cardiovascular disease in patients who are undergoing maintenance
      hemodialysis (HD). Continuous monitoring of central hemodynamic variables may
      provide valuable information to improve volume control, particularly in patients
      with left ventricular dysfunction. Sixteen patients with end-stage renal disease
      who were undergoing long-term HD received an implantable hemodynamic monitor
      consisting of a subcutaneously implanted memory device and transvenous right
      ventricular (RV) lead with a pressure sensor. The implantable hemodynamic monitor
      continuously records heart rate, RV pressures, and estimated pulmonary arterial
      (PA) diastolic pressure, an estimate of left ventricular filling pressure. All
      patients underwent HD 3 times per week, and averages of rest hemodynamic values
      from the first, second, and third nights after HD during 12 weeks were analyzed.
      The third night always occurred after the weekend, when there was an extended
      interval between dialysis sessions. From the first night to the second night, RV
      systolic pressure increased by 10 +/- 8% (p <0.001), and estimated PA diastolic
      pressure increased by 16 +/- 14% (p <0.001). On the third night, RV systolic
      pressure increased by 14 +/- 12% (p <0.001), and estimated PA diastolic pressure
      increased by 23 +/- 18% (p <0.001) compared with the first night. In conclusion,
      the progressive pressure increments between dialysis sessions seen in this study
      suggest that the implantable hemodynamic monitor was a sensitive indicator for
      changes in volume load in patients who were undergoing HD treatment. The results
      also suggest that more frequent dialysis may avoid excessive pressure increase,
      but this needs to be investigated further in future studies.

PMID- 19101242
TI  - Morphology of the patent foramen ovale in asymptomatic versus symptomatic (stroke
      or transient ischemic attack) patients.
AB  - The clinical implications of patent foramen ovale (PFO) morphology are still
      debated. Quantitative analysis by transesophageal echocardiography (TEE) is
      helpful in characterizing PFO morphology. The aim of this study was to determine
      whether there were differences in the anatomy of PFOs on TEE in patients with and
      without recurrent cryptogenic stroke or transient ischemic attack. The results of
      TEE in 58 patients who had PFO closure for cryptogenic cerebrovascular accident
      (CVA) were compared with those in 58 consecutive asymptomatic patients with PFOs
      found incidentally on TEE. The data were analyzed for differences in PFO size
      (maximum separation of the septum primum and septum secundum), tunnel length
      (maximum overlap of the septum primum and septum secundum), the presence of
      atrial septal aneurysm (>11 mm mobility), the severity of shunting (mild, 3 to 9
      microbubbles; moderate, 10 to 30 microbubbles; severe, >30 microbubbles), the
      prominence of the Eustachian valve; and the presence of Chiari's network.
      Patients with CVAs had larger PFOs (3.9 +/- 1.6 vs 2.9 +/- 1.4 mm, p <0.001),
      longer tunnels (14 +/- 6 vs 12 +/- 6 mm, p = 0.05), and a greater frequency of
      atrial septal aneurysm (45% vs 21%, p <0.005) compared with controls. They also
      had a greater proportion of large (>or=4 mm) PFOs (46% vs 17%, p <0.001), long
      (>or=1 cm) tunnels (78% vs 55%, p <0.01), and severe shunting (16% vs 5%, p
      <0.06). The frequencies of prominent Eustachian valves and Chiari's network were
      not significantly different. In conclusion, PFOs in patients with cryptogenic
      CVAs are larger, have longer tunnels, and are more frequently associated with
      atrial septal aneurysms. This information should be considered when evaluating
      patients with cryptogenic CVAs.

PMID- 19101243
TI  - A propensity-matched study of the association of peripheral arterial disease with
      cardiovascular outcomes in community-dwelling older adults.
AB  - The association between peripheral arterial disease (PAD) and outcomes has not
      been studied in a propensity-matched population of community-dwelling older
      adults. A public-use copy of the Cardiovascular Health Study (CHS) data was
      analyzed to test the hypothesis that baseline PAD is associated with increased
      all-cause mortality and cardiovascular morbidity. Of the 5,795 CHS participants,
      5,630 had data on baseline ankle-brachial index, and 767 had PAD, defined as
      ankle-brachial index <0.9. Propensity scores for PAD were calculated for each
      participant using 66 baseline covariates and were used to match 679 pairs of
      participants with and without PAD. Matched Cox regression models were used to
      estimate associations of PAD with outcomes during a median follow-up period of
      7.5 years. Overall, 55% of matched participants died from all causes during 9,958
      patient-years of follow-up. All-cause mortality occurred in 61% (rate
      8,710/100,000 patient-years) and 50% (rate 6,503/100,000 patient-years) of
      participants, respectively, with and without PAD (matched hazard ratio for PAD vs
      no PAD 1.47, 95% confidence interval (CI) 1.23 to 1.76, p <0.0001). Prematch
      unadjusted, multivariable-adjusted, and propensity-adjusted hazard ratios for PAD
      associated all-cause mortality were 2.90 (95% CI 2.61 to 3.21, p <0.0001), 1.53
      (95% CI 1.36 to 1.71, p <0.0001), and 1.57 (95% CI 1.39 to 1.78, p <0.0001),
      respectively. Matched hazard ratios for PAD for incident heart failure and
      symptomatic PAD were 1.32 (95% CI 1.00 to 1.73, p = 0.052) and 3.92 (95% CI 2.13
      to 7.21, p <0.0001), respectively. In conclusion, in a propensity-matched well
      balanced population of community-dwelling older adults, baseline PAD was
      associated with increased all-cause mortality and cardiovascular morbidity.

PMID- 19101244
TI  - Echocardiographic parameters of mechanical synchrony in healthy individuals.
AB  - Definition and validation of the ranges of normal values and agreement among
      echocardiographic measures of mechanical synchrony in healthy subjects are mostly
      lacking. The aims of this study were (1) to assess the ranges of normal values
      for 5 tissue Doppler imaging parameters, real-time 3-dimensional
      echocardiographic measures, and speckle-tracking measures of mechanical
      synchrony; (2) to evaluate interinstitutional variability; (3) to compare the
      ranges of normal values with those reported in previous research; and (4) to
      analyze the agreement among all parameters in the same healthy subject. Time to
      peak systolic velocity (Ts), the delay between Ts at the basal septal and lateral
      segments, peak velocity difference, strain derived by tissue Doppler imaging, Ts
      derived by tissue synchronization imaging, systolic synchrony index (SSI) derived
      by real-time 3-dimensional echocardiography, and longitudinal and radial strain
      derived by speckle tracking were prospectively collected and analyzed at 2
      different institutions in 160 consecutive healthy subjects. The ranges of normal
      values, expressed as means +/- 2 SDs, were 30.32 +/- 29.36 ms for the SD of Ts,
      15.51 +/- 99.88 ms for septal-lateral delay, 60.75 +/- 81.62 ms for peak velocity
      difference, 33.07 +/- 29.96 ms for tissue synchronization imaging, 34.16 +/-
      23.26 ms for the SD of strain, 2.74 +/- 2.16% for SSI, 28.91 +/- 23.02 ms for the
      SD of longitudinal strain, and 10.4 +/- 6.31 ms for radial strain. There was
      large interinstitutional variability for all parameters. Three-dimensional SSI
      and radial strain were within the published upper range limit for healthy
      subjects. Ninety percent of healthy subjects were consistently classified to be
      synchronous by 1 parameter. With a composite index, more subjects than expected
      showed dyssynchrony (10% vs 2.5%). In conclusion, 3-dimensional SSI and radial
      strain were the most reproducible parameters and consistently discriminated
      normal healthy subjects from the cardiac resynchronization therapy volume
      responders.

PMID- 19101245
TI  - A simple and safe technique for esophagojejunostomy using the hemidouble stapling
      technique in laparoscopy-assisted total gastrectomy.
AB  - In laparoscopy-assisted total gastrectomy, esophagojejunostomy is technically
      difficult. We describe a safe and simple technique for circular-stapled
      esophagojejunostomy. After mobilization of the stomach and the esophagus, a
      semicircumferential esophagotomy is made at the anterior esophageal wall. An
      anvil of a circular stapling device, secured with a Prolene suture (Ethicon, Inc,
      Somerville, NJ), is introduced via the esophagotomy. The suture is advanced
      anteriorly so that the center rod penetrates the esophageal wall. The esophagus
      is staple transected at this point. The circular-stapled esophagojejunostomy is
      then performed using the hemidouble stapling technique. Laparoscopy-assisted
      total gastrectomies were performed in 10 patients with gastric cancers. All
      patients were completed laparoscopically without any complications. The time of
      anvil placement was 9 minutes in median. Although a wound infection occurred in 1
      patient, there were no major complications. There was no mortality in this
      series. Esophagojejunostomy using this technique is safe and simple. Its
      practical value is the elimination of the need for pursestring suture placement.

PMID- 19101246
TI  - Pancreatic duct holder for facilitating duct-to-mucosa pancreatojejunostomy after
      pancreatoduodenectomy.
AB  - Duct-to-mucosa pancreatojejunostomy after pancreatoduodenectomy may be
      technically difficult, particularly in cases in which the remnant pancreas is
      soft with a small main pancreatic duct. We devised a pancreatic duct holder for
      duct-to-mucosa pancreatojejunostomy. The holder has a cone-shaped tip. A one
      third circle of the tip is cut away, which makes a slit. As the tip is inserted
      gently into the pancreatic duct, the duct can be adequately expanded. The holder
      provides a good surgical field for anastomosis. A slit of the tip allows needle
      insertion. The holder facilitates stitches of the jejunum also. Twelve patients
      underwent pancreatoduodenectomy, followed by duct-to-mucosa pancreatojejunostomy
      using the holder. The holder allowed 8 or more stitches in duct-to-mucosa
      anastomosis, even in patients with a small pancreatic duct. No patients developed
      prolonged pancreatic leakage or pancreatic fistula postoperatively. In
      conclusion, the pancreatic duct holder is a simple and useful tool for
      facilitating duct-to-mucosa pancreatojejunostomy.

PMID- 19101247
TI  - Implications of laparoscopy on surgery residency training.
AB  - BACKGROUND: With the advent of laparoscopy, many traditional junior-level cases
      now require advanced laparoscopic skill. We sought to ascertain the implications
      of laparoscopy on residency training through the use of a large national
      database. METHODS: American College of Surgeons National Surgical Quality
      Improvement Program data were gathered for patients undergoing elective open and
      laparoscopic inguinal herniorrhaphy, appendectomy, and partial colectomy during
      2005 and 2006. Cases were stratified by resident level and compared using
      univariate analysis. RESULTS: A total of 14,729 cases were performed during the
      study period. For inguinal hernia repair, 72% of open repairs were performed by
      postgraduate year 3 residents or below versus 41% of laparoscopic repairs (P <
      .0001). Similarly, 61% of open appendectomies were performed by postgraduate year
      3 residents or below compared with 48% of laparoscopic appendectomies (P <
      .0001). Forty-six percent of open colectomies were performed by postgraduate year
      3 and postgraduate year 4 residents versus 33% of laparoscopic resections (P <
      .0001). CONCLUSIONS: These data show an upward shift in cases traditionally
      performed by junior-level residents. The implications of this shift are unknown
      but may lead to decreased surgical experience during the early years of training.

PMID- 19101248
TI  - Efficacy of cognitive feedback in improving operative risk estimation.
AB  - BACKGROUND: Decision-making is an essential skill for surgeons, but systematic
      objective feedback is lacking. Cognitive feedback provides information about how
      risk factors relate to outcomes, and how individual surgeons mentally synthesize
      these relationships. METHODS: Pre-feedback, we assessed accuracy and reliability
      of 105 trainee surgeons'/medical students' estimates of operative mortality for
      major surgery for 28 patient vignettes with varying risk factors, using a
      published risk model as a gold standard. Post-feedback, participants were
      retested on a second case set. RESULTS: Post-feedback, both groups' estimates
      became more reliable. Pre-feedback, medical students were less accurate than
      trainee surgeons; post-feedback, their accuracy improved to match that of trainee
      surgeons, who did not improve further. CONCLUSIONS: Cognitive feedback improved
      risk estimate reliability in both groups and accuracy in the medical students
      group. Lack of improvement in the surgical group implies a ceiling effect. These
      findings have implications for training and assessment of surgical decision
      making.

PMID- 19101249
TI  - Acquiring basic surgical skills: is a faculty mentor really needed?
AB  - BACKGROUND: We evaluated the impact of expert instruction during laboratory-based
      basic surgical skills training on subsequent performance of more complex surgical
      tasks. METHODS: Forty-five junior residents were randomized to learn basic
      surgical skills in either a self-directed or faculty-directed fashion. Residents
      returned to the laboratory 2 days later and were evaluated while performing 2
      tasks: skin closure and bowel anastomosis. Outcome measures included Objective
      Structured Assessment of Technical Skill, time to completion, final product
      quality, and resident perceptions. RESULTS: Objective Structured Assessment of
      Technical Skill, time to completion, and skin esthetic ratings were not better in
      the faculty-directed group, although isolated improvement in anastomotic leak
      pressure was seen. Residents perceived faculty-directed training to be superior.
      CONCLUSIONS: Our data provided minimal objective evidence that faculty-directed
      training improved transfer of learned skills to more complex tasks. Residents
      perceived that there was a benefit of faculty mentoring. Curriculum factors
      related to training of basic skills and subsequent transfer to more complex tasks
      may explain these contrasting results.

PMID- 19101250
TI  - Psychometric properties of an integrated assessment of technical and
      communication skills.
AB  - PURPOSE: The Integrated Procedural Performance Instrument (IPPI) consists of
      clinical scenarios in which bench-top models are positioned to simulated
      patients. Trainees are required to perform technical skills while engaging with
      the patient. The purpose of this study was to determine whether an IPPI format
      examination could discriminate between different levels of trainees. METHODS:
      Sixteen fourth-year medical students and 16 first-year surgery residents
      participated in 4 IPPI scenarios. Videotaped performances were scored by 2
      blinded independent clinician raters on previously validated instruments:
      checklist of technical skills, Global Rating Scale of technical skills, and
      communication scale. We conducted separate mixed design analyses of variance
      (level x cases) on the 3 scales. RESULTS: Residents performed better than medical
      students on the checklist (74% vs 60%, P < .05), the Global Rating Scale of
      technical skills (75% vs 56%, P < .01), and the coherence communication subscale
      (79% vs 69%, P < .05). CONCLUSIONS: An IPPI examination discriminated between
      students' and residents' technical skills and coherence in communication skills.
      It also highlighted a potential gap in the training of residents' communication
      skills.

PMID- 19101251
TI  - A pilot study to integrate an immersive virtual patient with a breast complaint
      and breast examination simulator into a surgery clerkship.
AB  - BACKGROUND: We aimed to determine if an immersive virtual patient (VP) with a
      breast complaint and a breast mannequin could prepare third-year medical students
      for history-taking (HT) and clinical breast examination (CBE) on a real patient.
      METHODS: After standardized instruction in breast HT and CBE, students (n = 21)
      were randomized to either an interaction with a VP (experimental) or to no VP
      interaction (control) before seeing a real patient with a breast complaint.
      Participants completed baseline and exit surveys to assess confidence regarding
      their HT and CBE skills. RESULTS: Students reported greater confidence in their
      HT (Delta value = 1.05 +/- 1.28, P < .05) and CBE skills (Delta value = 1.14 +/-
      .91, P < .05) and less anxiety when performing a CBE (Delta value = -.76 +/-
      1.10, P < .05). The VP intervention group had a significantly higher mean HT
      confidence than the control group at the conclusion of the study (4.27 +/- .47 vs
      3.50 +/- .71, respectively, P < .05). CONCLUSIONS: A single interaction with a VP
      with a breast complaint and breast mannequin improves student confidence in
      breast HT during a surgery clerkship.

PMID- 19101252
TI  - Moral distress in the third year of medical school; a descriptive review of
      student case reflections.
AB  - BACKGROUND: Medical students may find certain clinical experiences particularly
      difficult. Moral distress occurs when a trainee sees a situation or behavior as
      undesirable, but, because of a position in the hierarchy, declines to address the
      problem. To prompt our students to reflect on such experiences, students are
      required to submit a brief case description and are assigned to mentor groups to
      discuss cases. METHODS: After exemption from our Institutional Review Board, a
      database of student submissions was de-identified. A total of 192 case
      descriptions were analyzed by a single reviewer to identify recurrent themes.
      Submissions were categorized in a binary fashion as higher or lower levels of
      distress. Frequency and correlation with levels of distress were assessed for
      each theme. RESULTS: Sixty-seven percent of the submissions were classified as
      higher distress. Seven major themes were identified, the most common being
      problems of communication (n = 179). Those students taking action correlated to
      lower distress. CONCLUSIONS: Our review shows that specific situations can be
      expected to generate moral distress in trainees. Addressing such distress may
      support the ongoing professional growth of trainees.

PMID- 19101253
TI  - Teaching communication skills using the integrated procedural performance
      instrument (IPPI): a randomized controlled trial.
AB  - BACKGROUND: The Integrated Procedural Performance Instrument (IPPI) uses various
      bench-top models positioned to standardized patients (SP) to recreate realistic
      clinical encounters. This study assessed the effectiveness of using an IPPI
      format as a teaching tool for communication skills. METHOD: Thirty-two
      participants underwent 2 videotaped IPPI scenarios before randomization into 2
      groups--experimental (SP-led feedback) or control (no feedback). Participants
      then completed 2 further IPPI format scenarios. Videotapes were scored by 2
      blinded independent raters using validated assessment scales (communication and
      technical). RESULTS: The experimental group performed significantly better on the
      communication scores following feedback compared with the control group (mean 77%
      vs 66%, P < .05). No difference in scores for technical skills post-intervention
      were demonstrated (checklist: experimental mean = 64% vs control = 59%, P = .40;
      global ratings: experimental mean = 66% vs no control = 62%, P = .37).
      CONCLUSIONS: The IPPI is an effective tool for teaching communication skills in
      residents and medical students and should be considered for incorporation into
      undergraduate and surgical curricula.

PMID- 19101254
TI  - Low-fidelity exercises for basic surgical skills training and assessment.
AB  - BACKGROUND: The goal of this study was to develop and validate low-fidelity
      exercises for basic surgical skills training and assessment. METHODS: Five low
      fidelity exercises were developed and administered to 40 participants.
      Participants were classified as novice or proficient based on level of training.
      Objective metrics were used for scoring. The cost for assembling 1 complete set
      of 5 exercises and all necessary supplies for practice and evaluation was $150.
      Once this set was assembled, the subsequent cost for replacement material was
      $5/participant examined. RESULTS: Twenty-four participants were categorized as
      novice and 16 as proficient. Proficient participants scored significantly higher
      than novice participants (P <.05) for exercises assessing needle-driving skills,
      2-hand coordination, and knot tying, thus establishing construct validity.
      Cronbach's alpha coefficient for internal consistency was .78, which demonstrates
      the exercises' reliability as a testing instrument. CONCLUSIONS: These data
      provide preliminary evidence of construct validity and internal consistency for a
      cost-effective series of low-fidelity basic surgical skills exercises.

PMID- 19101255
TI  - What is the ideal interval between training sessions during proficiency-based
      laparoscopic simulator training?
AB  - BACKGROUND: The aim of this study was to identify the ideal interval between
      training sessions in a proficiency-based laparoscopic suturing simulator
      curriculum. METHODS: We analyzed performance data from 3 randomized controlled
      trials of novices (n = 66) who followed a similar proficiency-based simulator
      curriculum in laparoscopic suturing on the Fundamentals of Laparoscopic Surgery
      model. The change in performance and intertraining interval were correlated.
      RESULTS: Overall participant performance improved from 530 +/- 58 seconds at
      baseline to 81 +/- 14 seconds at training completion (P < .001). Intertraining
      intervals ranged from 1 to 43 days and performance change between training
      sessions varied widely. There was no correlation of performance change with
      intertraining interval (r = .05, P = .30). Performance deterioration was similar
      at different intertraining intervals. Shorter intervals were associated, however,
      with shorter training duration (r = .35, P = .005). CONCLUSIONS: No association
      was found between intertraining interval and change in performance during
      proficiency-based laparoscopic simulator training but shorter intervals were
      associated with improved skill acquisition. Further study is needed to confirm
      these findings.

PMID- 19101256
TI  - Propofol infusion syndrome in adult cardiac surgery.
AB  - We report a case of rapid and progressive severe metabolic acidosis in the
      postoperative period after coronary artery bypass grafting. After exclusion of
      potential causes for this phenomenon, it was attributed to perioperative
      intravenous propofol infusion causing propofol infusion syndrome. We discontinued
      this intravenous agent resulting in a prompt and considerable improvement in the
      lactic acidosis and clinical condition in the subsequent 6 hours resulting in an
      uneventful recovery and hospital discharge.

PMID- 19101258
TI  - Sirolimus treatment for recurrent lymphangioleiomyomatosis after lung
      transplantation.
AB  - Pulmonary lymphangioleiomyomatosis is a rare disease that generally progresses to
      respiratory failure. We experienced a patient who had recurring
      lymphangioleiomyomatosis in the transplanted lungs. A chest computed tomographic
      scan showed a progressing emphysematous change. The patient had a subclinical
      extent of pan-circumferential stricture at the distal site of the left bronchial
      anastomosis. We treated the patient with sirolimus for three years. Chest
      computed tomography showed no sign of exacerbation during the late 3 years,
      whereas pulmonary function test revealed a slight increase after the use of
      sirolimus. Bronchial stricture also disappeared almost completely. This is the
      first reported case with sirolimus treatment for post-transplant recurrent
      lymphangioleiomyomatosis.

PMID- 19101257
TI  - Use of extracorporeal membrane oxygenation in the management of septic shock with
      severe cardiac dysfunction after Ravitch procedure.
AB  - We report the case of an 18-year-old patient who underwent Ravitch procedure for
      pectus carinatum and subsequently had septic shock develop with severe cardiac
      dysfunction requiring treatment with extracorporeal membrane oxygenation. We
      advocate the use of extracorporeal membrane oxygenation in adult patients with
      intractable cardiorespiratory failure due to sepsis post-thoracic surgery
      unresponsive to conventional therapy.

PMID- 19101259
TI  - Surgical treatment of an isolated origin of the right subclavian artery from the
      pulmonary artery.

PMID- 19101260
TI  - Myocardial infarction comes into the cold!

PMID- 19101261
TI  - No heroic measures: how soon is too soon to stop?

PMID- 19101262
TI  - Late results of conventional versus all-arterial revascularization based on
      internal thoracic and radial artery grafting.
AB  - BACKGROUND: Use of one or more arterial grafts to revascularize two-vessel and
      three-vessel coronary artery disease has been shown to improve coronary artery
      bypass graft surgery (CABG) survival. Yet, the presumed long-term survival
      benefits of all-arterial CABG have not been quantified. METHODS: We compared
      propensity-adjusted 12-year survival in two contemporaneous multivessel primary
      CABG cohorts with all patients receiving 2 or more grafts: (1) all-arterial
      cohort (n = 612; 297 three-vessel disease [49%]); and (2) single internal
      thoracic artery (ITA) plus saphenous vein (SV) cohort (n = 4,131; 3,187 three
      vessel disease [77%]). RESULTS: Early (30-day) deaths were similar for the all
      arterial and ITA/SV cohorts (8 [1.30%] versus 69 [1.67%]) whereas late mortality
      was substantially greater for the ITA/SV cohort (85 [13.9%] versus 1,216 [29.4%];
      p < 0.0001). The risk-adjusted 12-year survival was significantly better for all
      arterial (with a risk ratio [RR] = 0.60; 95% confidence interval [CI]: 0.48 to
      0.75; p < 0.001), but this benefit was true only for three-vessel disease (RR =
      0.58; 95% CI: 0.43 to 0.78; p < 0.001) and not for two-vessel disease (RR = 0.97;
      95% CI: 0.66 to 1.43; p = 0.89). The all-arterial survival benefit was also true
      for varying risk subcohorts: no diabetes mellitus (RR = 0.50; 95% CI: 0.37 to
      0.69), diabetes mellitus (RR = 0.77; 95% CI: 0.56 to 1.07), ejection fraction 40%
      or greater (RR = 0.60; 95% CI: 0.45 to 0.78), and ejection fraction less than 40%
      (RR = 0.62; 95% CI: 0.40 to 0.98). Lastly, the multivariate analysis indicated a
      strong long-term effect of completeness of revascularization, particularly for
      all-arterial patients, so that compared with patients with two grafts, survival
      was significantly better when three grafts (RR = 0.54; 95% CI: 0.33 to 0.87) or
      four grafts (RR = 0.40; 95% CI: 0.21 to 0.76) were completed. CONCLUSIONS: All
      arterial revascularization is associated with significantly better 12-year
      survival compared with the standard single ITA with saphenous vein CABG
      operation, in particular for triple-vessel disease patients. The completeness of
      revascularization of the underlying coronary disease is critical for maximizing
      the long-term benefits of arterial-only grafting.

PMID- 19101263
TI  - Subjective memory symptoms in surgical and nonsurgical coronary artery patients:
      6-year follow-up.
AB  - BACKGROUND: Self-reported cognitive and memory complaints after coronary artery
      bypass graft (CABG) operations are common. Several studies have attempted to
      quantify the incidence of such complaints and to examine the relationship between
      subjective and objective cognitive functioning, but the etiology and longitudinal
      course of these self-reports remain unclear. METHODS: Measures of subjective
      memory complaints were compared in two groups: 220 CABG patients and 92
      nonsurgical cardiac patients at 3 months, and 1, 3, and 6 years. At 6 years,
      additional measures were used to quantify memory self-assessment. The frequency
      of subjective complaints at each time point was determined, and associations with
      objective cognitive performance as well as depression were examined. RESULTS: At
      early (3-month or 1-year) follow-up, subjective memory complaints were reported
      more often by the CABG than the nonsurgical group (45.5% vs 17.0%, p < 0.0001).
      By 6 years, the frequency of complaints was similar (52%) in both groups.
      Subjective memory ratings were significantly correlated with performance on
      several memory tests at 6 years. This relationship was not confounded by
      depression. CONCLUSIONS: Subjective memory complaints are more frequent early in
      follow-up in patients undergoing CABG than in controls, but are similar by 6
      years. The increase in subjective complaints over time may be related to
      progression of underlying cerebrovascular disease. Unlike previous studies, we
      found that subjective memory assessments were correlated with objective
      performance on several memory tests. Although subjective memory complaints are
      more common in patients with depression, they cannot be explained by depression
      alone.

PMID- 19101264
TI  - Invited commentary.

PMID- 19101265
TI  - Cerebral oxygen desaturation predicts cognitive decline and longer hospital stay
      after cardiac surgery.
AB  - BACKGROUND: Previous studies have reported an 11% to 75% incidence of
      postoperative cognitive decline among cardiac surgery patients. The INVOS
      Cerebral Oximeter (Somanetics Corp, Troy, MI) is a Food and Drug Administration
      approved device that measures regional cerebral oxygen (rSo(2)) saturation. The
      purpose of this study is to examine whether decreased rSo(2) predicts cognitive
      decline and prolonged hospital stay after coronary artery bypass grafting (CABG).
      METHODS: The rSo(2) was monitored intraoperatively in a cohort of primary CABG
      patients. Patients were prospectively randomized to a blinded control group or an
      unblinded intervention group. Cognitive function was assessed preoperatively,
      postoperatively, and at 3 months using a battery of standardized neurocognitive
      tests. Cognitive decline was defined as a decrease of one standard deviation or
      more in performance on at least one neurocognitive measure. The rSo(2)
      desaturation score was calculated by multiplying rSo(2) below 50% by time
      (seconds). Multivariate logistic regression models were used to assess cognitive
      decline and hospital stay. The change in cognitive performance was also assessed
      using a multivariate linear regression model. RESULTS: Patients with rSo(2)
      desaturation score greater than 3,000%-second had a significantly higher risk of
      early postoperative cognitive decline [p = 0.024]. Patients with rSo(2)
      desaturation score greater than 3,000%-second also had a near threefold increased
      risk of prolonged hospital stay (>6 days) [p = 0.007]. CONCLUSIONS:
      Intraoperative cerebral oxygen desaturation is significantly associated with an
      increased risk of cognitive decline and prolonged hospital stay after CABG.

PMID- 19101266
TI  - Myocardial revascularization by left ventricular assisted beating heart is
      associated with reduced systemic inflammatory response.
AB  - BACKGROUND: The present study was designed to investigate whether use of left
      ventricular assisted technique (LVA) in beating-heart myocardial
      revascularization would exert less impact on patients' inflammatory response, as
      compared with minimal extracorporeal circulation (MECC). METHODS: Seventy-three
      consecutive high-risk patients undergoing myocardial revascularization were
      randomly assigned either to LVA (group A) or to MECC (group B). Monocyte count
      and plasma concentration of C-reactive protein, inflammatory cytokines
      interleukin-1beta, interleukin-6, and tumor necrosis factor-alpha, and
      polymorphonuclear elastase were measured at baseline and at various time points
      postoperatively. RESULTS: Preoperative clinical and demographic data did not
      differ between the two groups. The two groups also were similar with respect to
      mortality, number of grafts performed, duration of extracorporeal circulation,
      and need for inotropes. However, LVA was associated with significantly less
      inflammatory response postoperatively compared with MECC, as indicated by a
      significant difference in interleukin-6 (p = 0.002), C-reactive protein (p =
      0.002), monocyte percentage (p = 0.006), tumor necrosis factor-alpha (p = 0.002),
      and polymorphonuclear elastase (p = 0.001). CONCLUSIONS: High-risk patients
      undergoing beating-heart myocardial revascularization with LVA show reduced
      inflammatory response compared with patients treated with the MECC.

PMID- 19101267
TI  - Invited commentary.

PMID- 19101268
TI  - Intracoronary shunt prevents ischemia in off-pump coronary artery bypass surgery.
AB  - BACKGROUND: The purpose of this study was to evaluate the role of intracoronary
      shunt during off-pump coronary artery bypass surgery. METHODS: Fifty-six patients
      undergoing off-pump coronary artery bypass using the left internal mammary artery
      to bypass the left anterior descending coronary artery were randomly assigned to
      have the bypass performed with intracoronary shunt or by occlusive snaring.
      Ischemia during grafting was monitored by tissue Doppler. Hemodynamic status and
      indicators of ischemia were monitored, and on-table and postoperative angiography
      were performed. RESULTS: In patients with retrograde filling of the left anterior
      descending coronary artery, ischemia did not develop, but occlusion of
      antegradely perfused vessels caused ischemia in 26 of 33 patients. Ischemia was
      reversed in 14 of 16 shunted patients, and in 3 of 17 nonshunted cases (p =
      0.004). Angiography showed a trend toward improved on-table angiographic results
      in shunted patients. After 3 months, graft patency was 100%, but 1 patient
      treated without shunt required reintervention and 15 patients had new
      angiographic lesions, equally distributed between shunted and nonshunted
      patients. CONCLUSIONS: Intracoronary shunt prevents ischemia during grafting of
      the left anterior descending coronary artery and provides satisfactory immediate-
      and short-term graft patency.

PMID- 19101269
TI  - Invited commentary.

PMID- 19101270
TI  - Saphenous vein conduits harvested by endoscopic technique exhibit structural and
      functional damage.
AB  - BACKGROUND: Injury to the saphenous vein endothelium during harvest impacts
      patency after coronary artery bypass graft surgery. Many centers are adopting
      endoscopic saphenous vein harvest (ESVH) instead of using the traditional open
      saphenous vein harvest (OSVH) technique. Our objective was to compare the effects
      of ESVH and OSVH on the structural and functional viability of saphenous vein
      endothelium using multiphoton imaging, immunofluorescence, and biochemical
      techniques. METHODS: Ten patients scheduled for coronary artery bypass graft
      surgery were prospectively identified. Each underwent ESVH for one portion and
      OSVH for another portion of the saphenous vein. A 1-cm segment from each portion
      was immediately transported to the laboratory for processing. The vessel segments
      were labeled with fluorescent markers to quantify cell viability (esterase
      activity), calcium mobilization, and generation of nitric oxide. Samples were
      also labeled with immunofluorescent antibodies to visualize caveolin, endothelial
      nitric oxide synthase, von Willebrand factor, and cadherin, and extracted to
      identify these proteins using Western blot techniques. All labeling, imaging, and
      image analysis was done in a blinded fashion. RESULTS: Esterase activity was
      significantly higher in the OSVH group (p < 0.0001). Similarly, calcium
      mobilization and nitric oxide production were significantly greater in the OSVH
      group (p = 0.0209, p < 0.0001, respectively). Immunofluoresence and Western blot
      techniques demonstrated an abnormal alteration in distribution of caveolin and
      endothelial nitric oxide synthase in the ESVH group. CONCLUSIONS: Our study
      indicates that ESVH has a detrimental effect on the saphenous vein endothelium,
      which may lead to decreased graft patency and worse patient outcomes.

PMID- 19101271
TI  - Early and late outcomes of cardiac surgery in octogenarians.
AB  - BACKGROUND: Expanding demand for cardiac surgery in the elderly requires constant
      assessment of selection criteria and outcomes. METHODS: Records of consecutive
      patients 80 years old or greater (n = 355) having cardiac operations from
      September 1998 through May 2007 were reviewed. There were 172 isolated coronary
      bypass grafting (CABG), 73 isolated valve, 79 valve and CABG combined, and 31
      other procedures. RESULTS: Thirty-three (9.3%) deaths and 13 (3.7%) strokes
      occurred during the index hospital stay. Intensive care unit and hospital length
      of stay lasted 6.3 +/- 14.3 and 15.5 +/- 20.8 days, respectively. Overall
      cumulative 5-year survival was 65.5 +/- 3.3%, varying among procedures as
      follows: 67.9 +/- 4.4% for isolated CABG, 64.6 +/- 8.9% for valve surgery, 60.3
      +/- 7.3% for combined coronary and valve surgery, and 63 +/- 10.7% for other
      procedures (p = 0.23). Ninety-seven percent of survivors lived at home. Risk
      factors for hospital death were emergency status, preoperative renal dysfunction,
      and postoperative complications such as myocardial infarction, cardiac failure
      requiring intraaortic balloon pumping, acute renal failure requiring replacement
      therapy, stroke, and ventilator dependency exceeding 48 hours. Among hospital
      survivors, risk factors for late death were carotid artery disease, chronic lung
      disease, renal dysfunction, and the occurrence of postoperative complications.
      CONCLUSIONS: Long-term survival of octogenarians submitted to a wide variety of
      cardiac operations was satisfactory despite substantial rates of early
      complications and deaths. Most survivors were free from cardiac symptoms.
      Postoperative complications were stronger risk factors for hospital deaths than
      preoperative comorbidities and procedural variables. Their impact on long-term
      survival was also significant.

PMID- 19101272
TI  - Invited commentary.

PMID- 19101273
TI  - Mitral regurgitation due to myxomatous degeneration combined with bicuspid aortic
      valve disease is often due to prolapse of the anterior leaflet of the mitral
      valve.
AB  - BACKGROUND: This study examines the clinical, echocardiographic, surgical, and
      pathologic features of patients who had heart valve operations for combined
      congenital bicuspid aortic valve and mitral regurgitation due to degenerative
      disease of the mitral valve. METHODS: A retrospective review of 1595 patients who
      had procedures for mitral regurgitation due to degenerative disease of the mitral
      valve and 1820 patients who had procedures for congenital bicuspid aortic valve
      disclosed 29 patients who had combined diseases. RESULTS: The most common
      morphology of the bicuspid aortic valve was type 1 (fused right and left aortic
      cusps). Mitral regurgitation in 21 of 29 patients was caused by prolapse of the
      anterior leaflet, which was exceptionally large (mean height, 36.5 +/- 6.6 mm).
      Patients with prolapsed anterior leaflet of the mitral valve were younger (48 +/-
      13 years vs 58 +/- 16 years, p = 0.01) and 95% were men. The bicuspid aortic
      valve was incompetent in 19 of 21, and the aortic annulus exceeded 30 mm in 20 of
      21 patients. CONCLUSIONS: Patients with combined mitral regurgitation due to
      myxomatous degeneration and bicuspid aortic valve disease who require operations
      often have a large, prolapsing anterior leaflet of the mitral valve and dilated
      aortic annulus with aortic insufficiency due to cusp prolapse.

PMID- 19101274
TI  - Invited commentary.

PMID- 19101275
TI  - Outcomes of tricuspid valve repair and replacement: a propensity analysis.
AB  - BACKGROUND: The purpose of this study was to compare operative mortality and long
      term outcome of patients undergoing tricuspid valve replacement versus tricuspid
      valve repair. METHODS: From February 1986 to July 2006, 315 patients underwent
      tricuspid valve surgery including 93 replacements (72 biologic, 21 mechanical)
      and 222 repairs. To control for selection bias and varying comorbidities, a
      matched cohort of patients undergoing repair versus replacement was selected
      using propensity score analysis (68 patients in each group). RESULTS: In the
      propensity-matched cohorts, operative mortality was similar for tricuspid valve
      replacement (13% +/- 4%) and repair (18% +/- 5%; p = 0.64). Intensive care unit
      length of stay was similar between cohorts (replacement, 4 days; repair, 3 days;
      p = 0.45), but the replacements had a significantly longer hospital lengths of
      stay (9 days versus 6 days; p = 0.01). In the replacement cohort, survival was
      85% at 1 year, 79% at 5 years, and 49% at 10 years. In the repair cohort,
      survival rates were similar with 80% at 1 year, 72% at 5 years, and 66% at 10
      years (p = 0.66 versus replacement). CONCLUSIONS: Surgical treatment of tricuspid
      valve disease, regardless of the operative approach, is associated with
      significant early and late mortality. However, there is no difference favoring
      tricuspid valve repair over replacement. Thus, we should not hesitate to consider
      tricuspid valve replacement for patients in whom we believe there is a reasonable
      chance for recurrence of regurgitation after repair.

PMID- 19101276
TI  - The 17-mm St. Jude Medical Regent valve is a valid option for patients with a
      small aortic annulus.
AB  - BACKGROUND: When aortic valve replacement is performed in patients with a small
      aortic annulus, prosthesis-patient mismatch is of concern. Such prosthesis
      patient mismatch may affect postoperative clinical status and survival. We
      investigated the outcomes of isolated aortic valve replacement performed with a
      17-mm mechanical prosthesis in patients with aortic stenosis. METHODS: Twenty
      three patients with aortic stenosis (mean age, 74.6 +/- 6.3 years) underwent
      isolated aortic valve replacement with a 17-mm St. Jude Medical Regent
      prosthesis. Mean body surface area was 1.41 +/- 0.13 m(2). Preoperative
      echocardiography yielded a mean aortic valve area of 0.36 +/- 0.10 cm(2)/m(2), a
      mean left ventricular-aortic pressure gradient of 68.4 +/- 25.3 mm Hg, and a mean
      left ventricular mass index of 200 +/- 69 g/m(2). RESULTS: There was no operative
      mortality, and there were no valve-related events. Echocardiography at 14.0 +/-
      10.0 months after aortic valve replacement showed a significant increase in the
      mean effective orifice area index (0.95 +/- 0.24 cm(2)/m(2)), decrease in the
      mean left ventricular-aortic pressure gradient (17.4 +/- 8.2 mm Hg), and decrease
      in the mean left ventricular mass index (124 +/- 37 cm(2)/m(2)). Prosthesis
      patient mismatch (effective orifice area index < 0.85 cm(2)/m(2)) was present in
      8 patients at discharge. In these patients as well as in those without prosthesis
      patient mismatch, the left ventricular mass index decreased remarkably during
      follow-up. CONCLUSIONS: Aortic valve replacement with a 17-mm Regent prosthesis
      appears to provide satisfactory clinical and hemodynamic results in patients with
      a small aortic annulus. Remarkable left ventricular mass regression during follow
      up was achieved irrespective of the effective orifice area index at discharge.

PMID- 19101278
TI  - Invited commentary.

PMID- 19101277
TI  - Ross operation in the adult: long-term outcomes after root replacement and
      inclusion techniques.
AB  - BACKGROUND: Dilatation of the pulmonary autograft is a major concern after root
      replacement for the Ross operation. The inclusion technique would avoid this
      drawback, but few data are available on the long-term results of this technique.
      We retrospectively analyze long-term results of both techniques. METHODS: Of 218
      patients undergoing the Ross operation between 1991 and 2006, 148 (68%) had root
      replacement and 70 (32%) underwent the inclusion technique. The mean age of the
      patients was 40 +/- 10 years (range, 16 to 64). Mean follow-up was 94 +/- 44
      months (range, 13 to 196). Echocardiographic controls were available in 197
      patients. Proximal aorta dilatation was defined as diameter > 40 mm. RESULTS: In
      the root and inclusion groups, 10-year overall survival was 94% +/- 4% and 97% +/
      4%, respectively. Freedom from autograft reoperation was 81% +/- 10% and 84% +/-
      13%, respectively. Main cause of reoperation was autograft dilatation in the root
      group (13 of 16) and valve prolapse in the inclusion group (5 of 6). Freedom from
      proximal aorta dilatation was 57% +/- 12% and 80% +/- 15%, respectively. In the
      root group, dilatations (n = 48) affected systematically the autograft sinuses or
      sinotubular junction, whereas in the inclusion group, dilatations (n = 10)
      affected principally the ascending aorta (8 of 10). Freedom from severe autograft
      regurgitation was 86% +/- 9% and 83% +/- 13%, respectively. Root technique,
      follow-up length, and preoperative aortic valve regurgitation were predictors of
      proximal aorta dilatation. CONCLUSIONS: In the long term, both techniques showed
      excellent survival and similar rates of autograft failure. For root replacement,
      autograft dilatation was the main cause of failure. For the inclusion technique,
      the autograft, but not the ascending aorta, was protected against dilatation and
      autograft valve prolapse was the main cause of failure.

PMID- 19101279
TI  - Midterm change of descending aortic false lumen after repair of acute type I
      dissection.
AB  - BACKGROUND: Persistent false lumen in the descending aorta after repair of acute
      type I dissection adversely affects long-term prognosis. In this study, we
      investigated changes of the descending aortic false lumen during the midterm
      postoperative period. METHODS: Postoperative computed tomographic (CT) images of
      122 patients who underwent conventional ascending with or without arch
      replacement for acute type I dissection were reviewed. Patency and width of false
      lumen and maximal diameter of the aorta were compared between early and last
      follow-up images. Changes were analyzed separately in the thoracic and abdominal
      segments. RESULTS: In early CT, thoracic false lumen was patent in 85 patients
      (69.7%), and abdominal false lumen was patent in 111 patients (91.0%). Among
      these, the false lumen remained patent after a mean interval of 33.6 months in 69
      patients (81.1%) and 105 patients (94.6%), respectively. In 58 patients (47.5%),
      the descending aorta dilated by 1 cm or more. Dilatation occurred more frequently
      in the thoracic aorta and in patients with patent or wide false lumens, larger
      aortic diameter, Marfan syndrome, younger age, and male sex. Meanwhile, shrinkage
      of thoracic false lumen occurred in 36 patients (29.5%). Such shrinkage occurred
      in 23 of 24 patients (95.8%) who had thrombosed and narrow false lumens in the
      thoracic aorta. CONCLUSIONS: Early postoperative characteristics of false lumen
      were helpful for predicting both dilation and regression. Our data show not only
      a high incidence of descending aortic dilatation after repair of acute type I
      dissection, but also shrinkage of thoracic false lumen in some patients. These
      findings can be used as control data for determining the benefit of more
      extensive or new surgical approaches.

PMID- 19101280
TI  - Invited commentary.

PMID- 19101281
TI  - Outcome after the modified Bentall technique with a long interposed graft to the
      left coronary artery.
AB  - BACKGROUND: The modified Bentall technique, which was reported by Svensson in
      1992, is an aortic root composite valve graft replacement involving
      reimplantation of the left coronary ostium with a long interposed graft wrapping
      behind the composite graft. The technique is technically advantageous,
      particularly for complicated or redo aortic roots. To justify the technique, the
      midterm outcome needs to be evaluated. METHODS: Since 1992, 40 patients (4 with
      Marfan syndrome) underwent the modified Bentall technique (Svensson's
      modification). The mean age was 54.7 +/- 13.6 years, and 32 patients (80.0%) were
      male. All hospital survivors have been consecutively followed with annual
      echocardiographic evaluations. Furthermore, in 2007, multislice computed
      tomography was performed at 4.7 +/- 3.5 years (maximum, 14.9 years)
      postoperatively in 30 patients who had preserved renal function. RESULTS: No
      patients have experienced any complications regarding the technique at the follow
      up of 5.7 +/- 4.0 years (maximum, 14.9 years), although there were 2 hospital
      deaths of emergency cases and 5 late deaths owing to noncardiac causes. In 35
      patients (92.1% of hospital survivors), no structural complications were detected
      by multislice computed tomographies of the 30 patients or coronary angiograms of
      the remaining 5 patients. The consecutive echocardiographic follow-ups showed
      well-preserved left ventricular function with the most recent ejection fraction
      being 0.581 +/- 0.078. CONCLUSIONS: This Svensson's modification technique was
      associated with favorable midterm outcomes by multislice computed tomography and
      consecutive echocardiographic evaluations, indicating long-lasting advantages as
      well as technical benefits. Thus, the technique can be considered as a helpful
      and justifiable alternative method.

PMID- 19101282
TI  - Invited commentary.

PMID- 19101283
TI  - Deep hypothermic circulatory arrest in patients with high cognitive needs: full
      preservation of cognitive abilities.
AB  - BACKGROUND: Owing to controversy regarding the efficacy and safety of deep
      hypothermic circulatory arrest (DHCA) during thoracic aortic surgery, we
      conducted a psychometric study in which high-cognitive patients and their
      informants were interviewed to determine whether DHCA had any adverse effect on
      their daily activities or work performance. METHODS: A total of 29 patients (18
      males, 11 females; age, 26 to 75 years; mean 52.6 years) whose jobs require high
      cognitive capability and who had undergone aortic surgery using DHCA (range, 17
      to 54 minutes; mean arrest time, 27.4 minutes) at Yale-New Haven Hospital were
      retrospectively studied. These 29 patients represented the responders among 45
      such patients to whom questionnaires were mailed. A control group of 21 high
      cognitive patients (20 males, 1 female; ages, 36 to 77 years; mean, 54.7 years)
      who underwent aortic surgery without DHCA were surveyed as well. During surgery,
      DHCA was used as the sole means of cerebral protection. The head was packed in
      ice, and carbon dioxide flooding of the field was used in all cases. The
      ascending aorta was resected with an open distal anastomosis and a hemiarch or
      total arch replacement. A 21-part questionnaire (adapted from A.F. Jorm's Short
      Form IQCODE and supplemented by our own questions) was distributed
      postoperatively to subjects and to their informants (generally a spouse). A value
      of 3 on the questionnaire indicated "not much change" from preoperative status (1
      indicated much worse and 5 indicated much improved). RESULTS: There were no
      statistically significant differences in any functional outcomes by study group
      (by patient: DHCA 3.01, control 3.09; by informant: DHCA 3.00, control 3.03; p >
      0.05). Mean values of the outcomes for study groups and control subjects were
      essentially identical and quite close to 3 (the value assigned to "not much
      change") for overall score, for occupational score, and for memory-related score.
      CONCLUSIONS: These data indicate that high-cognitive patients experienced very
      little cognitive change as a result of undergoing DHCA. Our assessment strongly
      supports the adequacy of straight DHCA as a cerebral protectant strategy during
      short- to moderate-duration circulatory arrest. We found excellent preservation
      of functional state and no difference from patients undergoing aortic surgery
      without DHCA.

PMID- 19101284
TI  - CardioWest (Jarvik) total artificial heart: a single-center experience with 42
      patients.
AB  - BACKGROUND: When implanted in patients with biventricular failure, the CardioWest
      total artificial heart has asserted itself over time as a reliable bridge-to
      transplant device that as yet is used by only a few international teams. The aim
      of this single-center retrospective study is to assess both the comorbidity and
      survival of patients awaiting heart transplants while receiving circulatory
      support with a CardioWest total artificial heart. METHODS: From 1990 to December
      2006, 42 patients received a CardioWest total artificial heart at our center.
      Mean age at the time of implantation was 45.7 +/- 9.5 years, and 40 patients
      (95%) were men. Idiopathic or dilated cardiomyopathy was diagnosed in 45.2% (n =
      19) of the patients and ischemic cardiomyopathy in 42.8% (n = 18). Average body
      surface area was 1.9 +/- 0.22 m(2). RESULTS: Duration of support was 1 to 292
      days (mean, 101 +/- 86 days). Twelve patients died (28.5%) while receiving device
      support, and 30 patients (71.5%) underwent transplantation. Actuarial survival
      rates for the transplanted patients were 90% (n = 25), 81% (n = 14), and 76% (n =
      10) at 1, 5, and 10 years, respectively. Causes of death during device support
      included multiorgan failure in 6 (50%), sepsis in 2, acute respiratory distress
      syndrome in 2, alveolar hemorrhage in 1, and other cause in 1. There were no
      device malfunctions that led to patient death. Adverse events included stroke in
      3 patients (7%) and infections in 35 patients (85%) during support. CONCLUSIONS:
      The CardioWest total artificial heart is an excellent bridge-to-transplant device
      for patients with biventricular failure. Our study demonstrates excellent safety,
      reliability, and efficiency. Exceptional outcome after transplantation underlines
      its capacity to aid in end-organ recovery.

PMID- 19101285
TI  - Platelet dysfunction in outpatients with left ventricular assist devices.
AB  - BACKGROUND: Thromboembolic and bleeding complications in outpatients with a left
      ventricular assist device are common and can be detrimental. A meticulous balance
      between anticoagulant and procoagulant factors is therefore crucial. However, in
      contrast to routinely performed plasmatic coagulation tests, platelet function is
      hardly ever monitored although recent reports indicated platelet dysfunction. We
      therefore differentially evaluated platelet function with four commonly used
      point-of-care devices. METHODS: In a cross-sectional design platelet function was
      assessed in 12 outpatients and 12 healthy matched volunteers using
      thrombelastography platelet mapping, thromboelastometry, platelet function
      analyzer, and a new whole blood aggregometer (Multiplate). RESULTS: Phenprocoumon
      produced an international normalized ratio of 3.5. It was associated with a
      twofold prolongation in the thromboelastometry clotting time (p < 0.001).
      Platelet function under high shear was severely compromised: collagen adenosine
      diphosphate closure times were 2.5-fold longer in patients than in volunteers (p
      < 0.001), and 50% of patients had maximal collagen adenosine diphosphate closure
      time values. Although antigen levels of von Willebrand factor were 80% higher in
      patients (p < 0.001), von Willebrand factor-ristocetin was subnormal in 5 of 12
      patients. Ristocetin-induced aggregation was also threefold higher in volunteers
      (p < 0.001), indicating an additional functional defect of platelets affecting
      the glycoprotein Ib-von Willebrand factor axis. The von Willebrand factor
      multimer pattern in patients also appeared abnormal. CONCLUSIONS: Multimodal
      antiplatelet monitoring showed markedly impaired platelet function in patients
      with a left ventricular assist device. Platelet dysfunction under high shear
      rates and abnormal ristocetin-induced aggregation is only partly attributable to
      low von Willebrand factor activity. These findings resemble the acquired von
      Willebrand syndrome that is associated with microaggregate formation and enhanced
      bleeding.

PMID- 19101286
TI  - Invited commentary.

PMID- 19101287
TI  - N-acetylcysteine in cardiovascular-surgery-associated renal failure: a meta
      analysis.
AB  - BACKGROUND: Clinical trials with N-acetylcysteine (NAC) in perioperative
      cardiovascular settings have shown inconsistent effects for renal endpoints. We
      aimed to systematically review these trials to ascertain its role in prevention
      of post-cardiovascular surgery acute renal failure. METHODS: We searched MEDLINE,
      EMBASE, Cochrane Renal Health Library, and Google Scholar for randomized
      controlled studies that evaluated NAC in adult patients undergoing cardiovascular
      surgery. Acute renal failure, acute renal failure requiring dialysis, and
      mortality were the primary outcomes. Additional outcomes studied were length of
      intensive care unit stay, postoperative serum creatinine, creatinine clearance,
      renal biomarkers, and adverse effects of NAC. RESULTS: Twelve studies comprising
      1,324 patients were found to be eligible. Meta-analytic estimates showed that NAC
      was not associated with reduction in acute renal failure (odds ratio [OR]: 0.89,
      95% confidence interval [CI]: 0.68 to 1.15), acute renal failure requiring
      dialysis (OR: 1.09, 95% CI: 0.57 to 2.09) or mortality (OR: 0.95, 95% CI: 0.53 to
      1.71). N-acetylcysteine was well tolerated but was not associated with any
      reduction in the length of intensive care unit stay. It had inconsistent effects
      on postoperative serum creatinine, creatinine clearance, and renal biomarkers.
      Subgroup analysis restricted to studies using intravenous NAC preparation showed
      a nonsignificant trend toward reduction in acute renal failure (OR: 0.81, 95% CI:
      0.61 to 1.08) without any significant change in other outcomes. CONCLUSIONS:
      Overall analysis of the existent literature shows that NAC is not beneficial in
      the prevention of post-cardiovascular surgery renal dysfunction. Routine use of
      NAC for this indication should be avoided.

PMID- 19101288
TI  - Dermal filler injection: a novel approach for limiting infarct expansion.
AB  - BACKGROUND: Early infarct expansion after coronary occlusion compromises
      contractile function in perfused myocardial regions and promotes adverse long
      term left ventricular (LV) remodeling. We hypothesized that injection of a tissue
      expanding dermal filler material into a myocardial infarction (MI) would
      attenuate infarct expansion and limit LV remodeling. METHODS: Fifteen sheep were
      subjected to an anteroapical MI involving approximately 20% of the LV followed by
      the injection of 1.3 mL of a calcium hydroxyapatite-based dermal filler into the
      infarct. Real-time three-dimensional echocardiography was performed at baseline,
      30 minutes after MI, and 15 minutes after injection to assess infarct expansion.
      Sixteen additional sheep were subjected to the same infarction and followed
      echocardiographically and hemodynamically for 4 weeks after MI to assess chronic
      remodeling. Eight animals had injection with dermal filler as described above
      immediately after MI, and 8 animals were injected with an equal amount of saline
      solution. RESULTS: All animals exhibited infarct expansion soon after coronary
      occlusion. The regional ejection fraction of the apex became negative after
      infarction, consistent with systolic dyskinesia. Injection of the dermal filler
      converted the apical wall motion from dyskinetic to akinetic and resulted
      immediately in significant decreases in global, regional, and segmental LV
      volumes. Chronically, relative to saline control, dermal filler injection
      significantly reduced LV end-systolic volume (62.2 +/- 3.6 mL versus 44.5 +/- 3.9
      mL; p < 0.05) and improved global ejection fraction (0.295 +/- 0.016 versus 0.373
      +/- 0.017; p < 0.05) at 4 weeks after infarction. CONCLUSIONS: Injection of an
      acellular dermal filler into an MI immediately after coronary occlusion reduces
      early infarct expansion and limits chronic LV remodeling.

PMID- 19101289
TI  - Invited commentary.

PMID- 19101290
TI  - Mild hypothermia to limit myocardial ischemia-reperfusion injury: importance of
      timing.
AB  - BACKGROUND: Hypothermia during ischemia has been shown to reduce myocardial
      reperfusion injury. We sought to establish the cardioprotective effect of very
      mild total-body hypothermia (<or= 2.5 degrees C) and to determine whether the
      application of hypothermia at different points during the ischemia-reperfusion
      period influenced the degree of myocardial salvage. METHODS: Rabbits were
      subjected to 30 minutes of myocardial ischemia followed by 3 hours of
      reperfusion. Twenty-five animals were maintained at normal temperature (39.5
      degrees C) throughout the experiment (W-W-W group). All other animals were cooled
      to reduce left atrial temperature 2.0 degrees C to 2.5 degrees C. Eleven animals
      reached goal temperature before coronary occlusion (C-C-C group), in 14 animals
      cooling was initiated at coronary occlusion (W-C0-C group), in 8 animals cooling
      was initiated 15 minutes after coronary occlusion (W-C15-C group), in 5 animals
      cooling was initiated 25 minutes after coronary occlusion (W-C25-C group), and in
      13 animals cooling was started concurrently with reperfusion (W-W-C group).
      Infarct size as a percentage of the risk area (I/AR) was determined by a double
      staining-planimetry technique. RESULTS: Goal temperature was achieved before
      reperfusion in the C-C-C and W-C0-C groups but was not achieved until the
      reperfusion period in the other treatment groups. Infarct size was 59.0 +/- 1.2%
      in the W-W-W group and was reduced in all cooling groups (C-C-C = 30.4 +/- 4.9%;
      W-C0-C = 33.4 +/- 5.0%; W-C15-C = 42.4 +/- 1.4%; W-C25-C = 44.1 +/- 2.3%; W-W-C =
      50.5 +/- 4.1%). The temperature at reperfusion correlated most strongly with
      infarct size (r = 0.72, p < 1 x 10(-12)). CONCLUSIONS: Very mild hypothermia
      affords a significant cardioprotective effect. Temperature at the time of
      reperfusion most strongly correlates with the degree of myocardial salvage.

PMID- 19101291
TI  - Regional heterogeneity of myocardial reperfusion injury: effect of mild
      hypothermia.
AB  - BACKGROUND: Mild hypothermia confers a myocardial protective effect that may make
      it a useful adjunct to reperfusion therapy for myocardial infarction (MI). The
      effect of temperature on the extent and distribution of myocardial reperfusion
      injury in a collateral deficient ovine model was studied. METHODS: Topical
      cooling maintained left atrial temperature at 39.5 degrees C (n = 8), 38.5
      degrees C (n = 5), 37.5 degrees C (n = 6), 36.5 degrees C (n = 6), or 35.5
      degrees C (n = 5) in sheep prior to 1 hour of coronary occlusion to produce an
      anteroapical myocardial risk area (AR) followed by 3 hours of reperfusion. A dual
      staining and planimetry technique was used to assess infarct size as a percentage
      of the AR in 3 myocardial short axis slices that included the entire AR (slice 1=
      most apical; slice 3= most basal). The subendocardial, midmyocardial, and
      subepicardial extent in short axis of the infarct was also assessed in each
      slice. Microspheres assessed transmural blood flow. RESULTS: At 39.5 degrees C
      there was a long-axis gradient in myocardial injury that was most severe at the
      apex and lessened toward the base. The midmyocardial region was most susceptible
      to injury at all long axis levels. Temperature reduction (as little as 1 degrees
      C) was associated with improved salvage that was most pronounced in the apical
      subendocardium and least in the basilar midmyocardium. Reperfusion at 39.5
      degrees C resulted in severe transmural microvascular injury (no-reflow) that was
      completely obviated at temperatures below 38.5 degrees C. CONCLUSIONS: Myocardial
      reperfusion injury varies over the long and short LV axes. Mild hypothermia
      preferentially improves myocardial salvage at the LV apex. Small temperature
      changes can dramatically affect microvascular integrity.

PMID- 19101292
TI  - Very mild hypothermia during ischemia and reperfusion improves postinfarction
      ventricular remodeling.
AB  - BACKGROUND: Mild hypothermia (< 4 degrees C) improves myocardial salvage after
      infarct reperfusion in animals and in early clinical studies. In this experiment
      the effect of mild hypothermia during ischemia and early reperfusion on long-term
      postinfarction left ventricular (LV) remodeling was assessed in an ovine infarct
      model. METHODS: In the initial phase of the experiment the effect of progressive
      degrees of hypothermia on infarct size was quantified. Thirty-eight male sheep
      were subjected to 1 hour of ischemia using a standardized anteroapical infarct
      followed by 3 hours of reperfusion. Temperature was maintained at either 39.5
      degrees C (n = 11), 38.5 degrees C (n = 7), 37.5 degrees C (n = 7), 36.5 degrees
      C (n = 7), or 35.5 degrees C (n = 6) for the entire period of ischemia and
      reperfusion. The area at risk (AR) and infarct size as a percentage of AR (I/AR)
      were determined with a double staining and planimetry technique. In the second
      phase of the study, chronic post-infarction remodeling was assessed in animals
      with nonreperfused infarcts (n = 6), 1 hour of ischemia followed by reperfusion
      at 39.5 degrees C (n = 6) and 1 hour of ischemia followed by reperfusion at 37.5
      degrees C (n = 6). Remodeling was determined at 8 weeks after infarction using
      echocardiography. RESULTS: The I/AR in the 39.5 degrees C, 38.5 degrees C, 37.5
      degrees C, 36.5 degrees C, and the 35.5 degrees C groups was 71.8 +/- 3.0%, 63.1
      +/- 1.9%, 49.4 +/- 1.4%, 38.7 +/- 1.4%, and 21.7 +/- 2.2%, respectively (p < 0.05
      between all groups). In the chronic study LV end systolic volume at 8 weeks after
      infarction was 81 +/- 8 mL in the nonreperfused group, 57 +/- 4 mL in the 39.5
      degrees C reperfusion group, and 41 +/- 3 mL in the 37.5 degrees C reperfusion
      group (p < 0.05 for between group differences). CONCLUSIONS: Subtle degrees of
      hypothermia can significantly improve immediate myocardial salvage and long-term
      LV remodeling after infarct reperfusion.

PMID- 19101293
TI  - Risk factors for mortality after the Norwood procedure using right ventricle to
      pulmonary artery shunt.
AB  - BACKGROUND: The purpose of this study was to describe the experience with staged
      surgical reconstruction of the hypoplastic left heart syndrome (HLHS) with a
      right ventricle to pulmonary artery conduit and to identify the risk factors that
      influence late outcome. METHODS: Between February 1998 and June 2007, 62 patients
      with HLHS underwent a Norwood procedure by using right ventricle to pulmonary
      artery conduit (median age, 9 days [range, 1 to 57]; median body weight 2.7 kg
      [range, 1.6 to 3.9 kg]). The subsequent 47 patients underwent a bidirectional
      Glenn procedure (stage 2). Thirty-two patients underwent a modified Fontan
      procedure (stage 3). Follow-up was complete (median, 32 months; range, 1 to 101).
      RESULTS: Hospital mortality after the Norwood procedure was 8% (5 of 62
      patients). Between stages, 9 patients died, 3 before stage 2 and 6 before stage
      3. There was 1 late death after stage 3. Overall survival was 76% (47 of 62). The
      estimated 1-year and and 5-year survival rates were 80% and 73%, respectively.
      Using the any-mortality as the endpoint, prematurity (gestational age <37 weeks),
      body weight less than 2.5 kg at stage 1 operation, and tricuspid regurgitation 2+
      or more were associated with mortality. Using Cox regression analysis, body
      weight less than 2.5 kg and tricuspid regurgitation 2+ or more were two
      independent factors associated with midterm survival. CONCLUSIONS: From 9 years
      of experience, despite good early survival after Norwood stage 1 palliation, low
      body weight and tricuspid valve regurgitation were still associated with worse
      outcome. More efforts should be made to improve the late results for patients
      with hypoplastic left heart syndrome.

PMID- 19101294
TI  - Risks and predictors of blood transfusion in pediatric patients undergoing open
      heart operations.
AB  - BACKGROUND: Blood transfusion in adults is associated with increased mortality
      and morbidity after cardiac operations. The aim of this study was to identify the
      main predictors of blood transfusion and explore the relationship between blood
      transfusion and adverse outcomes in a pediatric population. METHODS: We
      retrospectively analyzed a prospectively collected database (January 2002 to
      December 2003) of 657 consecutive pediatric patients undergoing open heart
      procedures in a tertiary pediatric cardiac center. Risk models were calculated
      for each blood product and for the total amount of blood transfused during the
      operation and in the first 24 hours. Postoperative adverse events were
      investigated after propensity score adjustment. RESULTS: During the postoperative
      period, 30 patients (4.6%) died, 80 (12.2%) sustained nonvascular pulmonary
      complications, and 113 (17.2%) had infection. The risk model for the total amount
      of blood transfusion included weight, preoperative creatinine clearance,
      preoperative mechanical ventilation, duration of operation and cross-clamp,
      surgeon, delayed chest closure, inotropic dose, and nitric oxide administration.
      Univariate analyses demonstrated significant associations between blood
      transfusion and occurrence of every complication except of neurologic events.
      After adjustment for propensity score and disease severity, the total amount of
      blood transfusion was independently associated with an increased risk for
      infections (odds ratio, 1.01; 95% confidence interval, 1.002 to 1.02; p = 0.01).
      Transfusion of platelets was associated with lower incidence of nonvascular
      pulmonary complications (odds ratio, 0.89; 95% confidence interval, 0.79 to 0.99;
      p = 0.049). CONCLUSIONS: The amount of blood transfusion is independently
      associated with infections but not with mortality.

PMID- 19101295
TI  - Invited commentary.

PMID- 19101296
TI  - Ventricular scoop in atrioventricular septal defect: relevance to simplified
      single-patch method.
AB  - BACKGROUND: The simplified single-patch repair for atrioventricular septal defect
      seems an attractive alternative to conventional methods despite controversies on
      its suitability in hearts with a large ventricular scoop. Inasmuch as previous
      anatomic studies were conducted before the advent of this technique, we revisited
      this malformation with the aim to identify morphologic markers that may aid
      patient selection. METHODS: We examined 43 heart specimens: 31 with the complete
      form and 12 with the partial form of the malformation. RESULTS: In 16 hearts with
      the complete form, the scoop extended antero-superiorly beyond the
      atrioventricular junction, resulting in a skewed shape of the scoop. By contrast,
      none of the other hearts had such an extension and the scoop was nearly
      symmetric. Hearts with the extension had significantly narrower diameters of the
      left ventricular outflow tract (median [interquartile range]: 22% [17% to 33%])
      than the complete form without the extension (38% [29% to 50%]; p = 0.01) and
      partial form (43% [25% to 50%]; p = 0.01). However, when the diameters were
      stratified with scoop depth, no obvious difference was found between the complete
      form with a deep scoop (defined as the depth of 60% or greater) and those with a
      shallower scoop (36% [24% to 49%] versus 28% [21% to 36%], respectively; p =
      0.146), indicating that antero-superior extension had more impact on the tract
      size than scoop depth. CONCLUSIONS: The antero-superiorly extended and skewed
      scoop could lead to asymmetric configuration of the valvar leaflets and outflow
      tract obstruction if the simplified technique is applied. Therefore, not only
      scoop depth but also the antero-superior extension should be recognized when
      repairing this lesion.

PMID- 19101297
TI  - Invited commentary.

PMID- 19101298
TI  - Donor-recipient race mismatch and graft survival after pediatric heart
      transplantation.
AB  - BACKGROUND: Black recipient race has been shown to predict poorer graft survival
      after pediatric heart transplantation. We analyzed our single-center experience
      comparing graft survival by race and the impact of donor-recipient race mismatch.
      METHODS: One hundred sixty-nine consecutive primary pediatric heart transplant
      patients were analyzed by donor and recipient race (white recipient, 99; black
      recipient, 60; other, 10). The groups were similar in preoperative
      characteristics. There were fewer donor-recipient race matches in blacks compared
      with whites (10 versus 71; p < 0.0001). RESULTS: Although 30-day and 6-month
      graft survival was similar for black and white recipients (93.9% and 85.8% versus
      93.3% and 83.3%, respectively), overall actuarial graft survival was
      significantly lower in blacks (p < 0.019). Blacks tended to have a higher
      incidence of positive retrospective crossmatch (n = 26, 43%) than whites (n = 29,
      29%), but this was not statistically significant (p = 0.053). The median graft
      survival for black recipients was 5.5 years compared with 11.6 years for whites.
      Donor-recipient race mismatch predicted poorer graft survival (5-year graft
      survival 48.9% versus 72.3%; p = 0.0032). The median graft survival for donor
      recipient race-matched patients was more than twice that for mismatched patients
      (11.6 years versus 4.4 years). Cox proportional hazard analysis showed that donor
      recipient race mismatch neutralized the effect of race on graft survival.
      CONCLUSIONS: Graft survival after pediatric heart transplantation is inferior for
      black recipients compared with white recipients. These differences may be
      explained by a high incidence of donor-recipient race mismatch, which also
      predicts poorer outcome for all racial groups with pediatric heart
      transplantation. These data may have implications for future donor allocation
      schemes.

PMID- 19101299
TI  - Expression of A and B blood group antigens on cryopreserved homografts.
AB  - BACKGROUND: The contribution of ABO blood group mismatching on the rate of
      cardiac homograft failure is uncertain. It has been shown that there is lack of
      expression of A and B blood group antigens on fresh and cryopreserved homograft
      valves. However, expression of these antigens on the homograft vessel conduit has
      not been reported. METHODS: Unused portions of cryopreserved pulmonary artery
      homografts (n = 16) were immunohistochemically stained and examined for
      expression of endothelial cell marker CD31 and A and B blood group antigens. The
      staining pattern for each antigen was described. Comparison of homograft donor
      blood group (as determined by immunostaining) to the blood group reported by the
      homograft supplier was made. RESULTS: Staining of CD31 and A and B blood group
      antigens was poor on the luminal surface (tunica intima) of the homograft conduit
      but strong in the vaso vasorum of the tunica media and adventitia. Homograft
      donor blood group was consistent with the reported donor blood group in 15 of 16
      specimens (4 group A, 3 group B, 8 group O). In one specimen (reported as group
      O), we detected strong expression of CD31 and A antigen on the endothelium of the
      vaso vasorum. CONCLUSIONS: Cryopreserved homografts strongly express A and B
      blood group antigens on well-preserved endothelial surfaces of the medial and
      adventitial vaso vasorum. The significance of this finding with regard to the
      immunologic response to mismatched ABO blood group antigens and homograft
      longevity is uncertain.

PMID- 19101300
TI  - Invited commentary.

PMID- 19101301
TI  - Comparison of pediatric cardiac surgical mortality rates from national
      administrative data to contemporary clinical standards.
AB  - BACKGROUND: Despite the superior coding and risk adjustment of clinical data, the
      ready availability, national scope, and perceived unbiased nature of
      administrative data make it the choice of governmental agencies and insurance
      companies for evaluating quality and outcomes. We calculated pediatric cardiac
      surgery mortality rates from administrative data and compared them with widely
      quoted standards from clinical databases. METHODS: Pediatric cardiac surgical
      operations were retrospectively identified by ICD-9-CM diagnosis and procedure
      codes from the Nationwide Inpatient Sample (NIS) 1988-2005 and the Kids'
      Inpatient Database (KID) 2003. Cases were grouped into Risk Adjustment for
      Congenital Heart Surgery, version 1 (RACHS-1) categories. In-hospital mortality
      rates and 95% confidence intervals were calculated. RESULTS: A total of 55,164
      operations from the NIS and 10,945 operations from the KID were placed into RACHS
      1 categories. During the 18-year period, the overall NIS mortality rate for
      pediatric cardiac surgery decreased from 8.7% (95% confidence interval, 8.0% to
      9.3%) to 4.6% (95% confidence interval, 4.3% to 5.0%). Mortality rates by RACHS-1
      category decreased significantly as well. The KID and NIS mortality rates from
      comparable years were similar. Overall mortality rates derived from
      administrative data were higher than those from contemporary national clinical
      data, The Society of Thoracic Surgeons Congenital Heart Surgery Database, or
      published data from pediatric cardiac specialty centers. Although category
      specific mortality rates were higher in administrative data than in clinical
      data, a minority of the relationships reached statistical significance.
      CONCLUSIONS: Despite substantial improvement, mortality rates from administrative
      data remain higher than those from clinical data. The discrepancy may be
      attributable to several factors: differences in database design and composition,
      differences in data collection and reporting structures, and variation in data
      quality.

PMID- 19101302
TI  - Thoracoscopy versus thoracotomy improves midterm musculoskeletal status and
      cosmesis in infants and children.
AB  - BACKGROUND: It has been postulated that video-assisted thoracoscopic surgery
      (VATS) achieves a better biometric and aesthetic outcome than conventional
      thoracic surgery (CTS), but data are lacking. We aimed to compare the midterm
      effects of both approaches in children. METHODS: Sixty-two infants and children,
      who underwent VATS (34; 55%) or CTS (28; 45%) for benign thoracic conditions,
      were evaluated at follow-up after a mean of 3.8 years (1 to 7 years). The
      patients underwent standardized clinical assessment of the skeletal system and
      function. The intercostal spaces were investigated for rib fusion by ultrasound.
      Patients (+/- parents) themselves, as well as clinicians, subsequently assessed
      the scars. RESULTS: Comparing the operated versus nonoperated sides, chest
      asymmetry was significantly less frequent after VATS versus CTS in the horizontal
      plane (mean relative difference 0.996 +/- 0.003 vs 0.964 +/- 0.008, p < 0.001)
      and in nipple location (mean relative difference 0.985 +/- 0.008 vs 0.949 +/-
      0.013, p = 0.047). The ranges of motion of the shoulder joints did not differ
      significantly. However, the incidence of scoliosis was lower in VATS patients (9%
      vs 54%, p < 0.001) and the intercostal spaces of the operated hemithoraces were
      narrower after CTS (p < 0.001). The Manchester scar assessment scores were in
      favor of VATS (mean 7.5 vs 13.1, p < 0.001). The visual analog scale scores
      recorded by patients-parents and independent observers were also significantly
      better after VATS. Patient satisfaction was less with CTS as 10% wanted to have
      the scar revised, compared with none in the VATS group. CONCLUSIONS: The
      thoracoscopic versus conventional approach to the thoracic cavity in children is
      associated with significantly less midterm musculoskeletal sequelae and a better
      cosmetic outcome.

PMID- 19101303
TI  - Persistent benefit from lung volume reduction surgery in patients with
      homogeneous emphysema.
AB  - BACKGROUND: The purpose of this study was to evaluate whether favorable short
      term results achieved by lung volume reduction surgery in selected patients with
      homogeneous emphysema would persist for longer periods. Their symptoms, lung
      function, and survival for several years were analyzed in comparison to patients
      with heterogeneous emphysema. METHODS: Two hundred fifty consecutive patients
      (105 women), mean (+/- standard deviation) age 64 +/- 8.4 years, with advanced
      emphysema underwent bilateral thoracoscopic lung volume reduction surgery. Forced
      expiratory volume in 1 second was 28% +/- 8% of predicted, 6-minute walking
      distance was 245 +/- 118 m, and Medical Research Council dyspnea score was 3.5 +/
      0.7. In 138 patients (55%) computed tomography revealed homogeneous emphysema
      (including 82 intermediate type) distribution and in 112 patients (45%)
      heterogeneous emphysema. Baseline characteristics were otherwise similar in the
      two groups that were prospectively observed for several years. RESULTS: Thirty
      day mortality was 2.4%. Both groups revealed significant improvements 3 months
      after lung volume reduction surgery: in homogeneous emphysema, predicted forced
      expiratory volume in 1 second was 38% +/- 14% (35% improvement), 6-minute walk
      distance was 324 +/- 87 m, and dyspnea score was 1.8 +/- 0.9 (p < 0.05 all
      outcomes). Corresponding results in heterogeneous emphysema were 44% +/- 15% (61%
      improvement), 382 +/- 95 m, and 1.3 +/- 0.9 points (p < 0.05 versus baseline; not
      significant versus homogeneous). Median time until predicted forced expiratory
      volume in 1 second and 6-minute walk distance had returned to baseline was 36
      months in both groups. One-year survival was similar in both groups. At 5 years,
      median survival without lung transplantation was 64% in the homogeneous and 73%
      in the heterogeneous group (Cox proportional hazard, 0.81; 95% confidence
      interval, 0.66 to 0.98; p = 0.03). CONCLUSIONS: In selected patients with
      homogeneous pulmonary emphysema, lung volume reduction surgery can be
      successfully performed with low perioperative mortality. Significant improvements
      in dyspnea, lung function, and exercise capacity are maintained for several
      years.

PMID- 19101304
TI  - Resection of pulmonary metastases from sarcoma: can some patients benefit from a
      less invasive approach?
AB  - BACKGROUND: Although video-assisted metastasectomy has been proposed for some
      solitary metastases, its value has not been investigated in patients with
      pulmonary metastases from sarcoma for which open resection remains the usual
      approach. METHODS: In all, 113 consecutive patients underwent curatively intended
      lung resection for metastases from sarcomas. Of these 113 patients, 31 were
      selected for a thoracoscopic wedge resection (group TS). These patients were
      compared with 29 patients operated on by thoracotomy but whose features could
      have made them possible candidates for a thoracoscopic resection (group TT).
      Follow-up was complete for all patients (mean follow-up, 34 months). RESULTS: No
      mortality occurred. No morbidity was observed in group TT, and 1 complication
      occurred in group TS. The mean postoperative hospital stay was 3.7 days for group
      TS and 6.2 days for group TT (p < 0.0001). Overall survival rates at 1, 3, and 5
      years were, respectively, 87.4%, 70.9%, and 52.5% in group TS, and 82.3%, 63.6%,
      and 34% in group TT (p = 0.20). Disease-free survival rates at 1 and 3 years
      were, respectively, 50.5% and 26.4% in group TS and 60% and 24.8% in group TT (p
      = 0.74). Local recurrence occurred in 1 patient in each group. Survival without a
      homolateral recurrence (i.e., in the operated lung) at 1 and 3 years was 66.7%
      and 44.4% in group TS and 83.5% and 45% in group TT, respectively (p = 0.54).
      CONCLUSIONS: In selected patients with a maximum of two pulmonary nodules,
      thoracoscopic resections yield survival rates similar to open resections while
      being less invasive and preserving the patient's ability to undergo possible
      repeat operations.

PMID- 19101305
TI  - Invited commentary.

PMID- 19101306
TI  - Mechanical pleurodesis aided by peritoneal drainage: procedure for hepatic
      hydrothorax.
AB  - BACKGROUND: Hepatic hydrothorax in the setting of decompensated cirrhosis is a
      challenging and common clinical problem. Traditional therapies such as diuretics
      and transjugular intrahepatic portosystemic shunts can be effective therapies in
      selected patients but in patients ineligible for, or intolerant of, these
      traditional therapies, few effective therapeutic options remain for the
      management of hepatic hydrothorax. METHODS: We present a series of 5 consecutive
      patients with refractory hepatic hydrothorax who underwent combined
      thorascopically guided mechanical and chemical pleurodesis aided by an
      intraperitoneal drain that prevented reaccumulation of the ascites while pleural
      inflammation and adhesion were progressing. We speculate that the prolonged
      contact between the parietal and visceral pleura allowed by prevention of
      reaccumulation of intraabdominal ascites and subsequent flux through the pleural
      space enhanced the efficacy of this procedure in comparison with those presented
      in the literature. RESULTS: Despite the fact that all of our patients presented
      with decompensated cirrhosis, the surgical procedure and subsequent
      hospitalization were tolerated well by our entire cohort. Colonization of the
      pleural and peritoneal drainage fluid was a common complication of this procedure
      but was not associated with prolonged morbidity or mortality. CONCLUSIONS: We
      present a therapy for the difficult clinical problem of refractory hepatic
      hydrothorax that may allow selected patients an opportunity for prolonged
      symptomatic control.

PMID- 19101307
TI  - Soluble triggering receptor expressed on myeloid cells-1 for diagnosing empyema.
AB  - BACKGROUND: Studies have shown that soluble triggering receptor expressed on
      myeloid cells-1 (sTREM-1) is upregulated by microbial products in the
      bronchoalveolar lavage fluid, and cerebrospinal fluid of patients with pneumonia
      and bacterial meningitis, respectively. Our goal was to evaluate whether sTREM-1
      in pleural fluid can distinguish pleural empyema from postthoracotomy-related
      pleural effusion and effusions of other etiologies. METHODS: Patients who
      presented with pleural effusion were identified through laboratory records. In
      addition to routine biochemical markers, differential white blood cells,
      cytology, Gram stain, and pleural fluid culture, pleural fluid sTREM-1 was
      measured by enzyme-linked immunosorbent assay using a commercial kit (R&D
      Systems, Minneapolis, MN). RESULTS: Eighty-nine patients were included in the
      study: 17 with empyema, 7 simple parapneumonic effusion, 18 transudate, 12
      postthoracotomy pleural effusion, 22 malignancy, 1 connective tissue disease, and
      12 with undetermined effusion. Mean levels of sTREM-1 were significantly higher
      in empyema than in postthoracotomy pleural effusion (687 +/- 479 pg/mL vs 34 +/-
      81 pg/mL, p < 0.0001, respectively) and in effusions of other etiologies (15 +/-
      54 pg/mL, p < 0.0001). A cutoff value of 114 pg/mL for pleural sTREM-1 achieved a
      sensitivity of 94% and a specificity of 93% in differentiating empyema from
      pleural effusions of other etiologies. The area under the receiver operating
      characteristic curve for pleural effusion sTREM-1 as a predictor for empyema was
      0.966. CONCLUSIONS: Our findings suggest that sTREM-1 in the pleural fluid can
      potentially assist clinicians in the differentiation of bacterial from
      nonbacterial pleural effusion, particularly in postthoracotomy pleural effusion.

PMID- 19101308
TI  - Clinical transplantation of initially rejected donor lungs after reconditioning
      ex vivo.
AB  - BACKGROUND: A major problem in clinical lung transplantation is the shortage of
      donor lungs. Only about 20% of donor lungs are accepted for transplantation. A
      method to evaluate and recondition lungs ex vivo has been tested on donor lungs
      that have been rejected for transplantation. METHODS: The donor lungs were
      reconditioned ex vivo in an extracorporeal membrane oxygenation (ECMO) circuit
      with STEEN solution (Vitrolife AB, Kungsbacka, Sweden) mixed with erythrocytes.
      The hyperoncotic solution dehydrates edematous lung tissue. Functional
      evaluations were performed with deoxygenated perfusate by varying the inspired
      fraction of oxygen. After the reconditioning, the lungs were kept immersed at 8
      degrees C in extracorporeal membrane oxygenation until transplantation was
      performed. RESULTS: Six of nine initially rejected donor lungs were reconditioned
      to acceptable function, and in six recipients, double lung transplantation was
      performed. Three-month survival was 100%. One patient has since died due to
      sepsis after 95 days, and one due to rejection after 9 months. Four recipients
      are alive and well without any sign of bronchiolitis obliterans syndrome 24
      months after the transplantation. CONCLUSIONS: The result from the present study
      is promising, and we continue to transplant reconditioned lungs.

PMID- 19101309
TI  - Survival of primary and repeat lung transplantation in the United States.
AB  - BACKGROUND: This study was undertaken to compare survival between primary and
      repeat lung transplant recipients and to identify survival predictors after
      repeat lung transplantation. METHODS: Data for 10,846 primary and 354 repeat lung
      transplant patients were extracted from the United Network for Organ Sharing
      registry. Propensity score matching was used to examine balance in the
      distribution of potential observed confounders and to match the sample in terms
      of the probability of repeat lung transplantation given pretransplant
      characteristics alone. Matching based on the propensity score was used to compare
      survival between the primary and repeat lung transplant groups. A Cox regression
      model was used to identify risk factors for death in the cohort of patients
      receiving lung transplant. RESULTS: Considerable bias between the primary and
      repeat lung transplant groups was found in the sample. Patients with high
      propensity scores tended to carry high-risk profiles. Propensity score matching
      revealed incomplete overlap of covariate distributions between primary and repeat
      transplant groups. For those subjects who could be matched for the set of
      potential confounding variables, no difference in survival time was observed
      between primary and repeat lung transplant patients. Functional status and serum
      creatinine level were the two clinically important risk factors for predicting
      the survival of repeat transplant patients. CONCLUSIONS: The current study
      revealed that direct comparison of the survival of primary and repeat lung
      transplant patients is biased by nonoverlap in the distribution of potential
      confounders. Using propensity score matching we adjusted for this bias and found
      that there was no significant difference in survival between first and second
      transplants.

PMID- 19101310
TI  - Primary palmoplantar hyperhidrosis and thoracoscopic sympathectomy: a new
      objective assessment method.
AB  - BACKGROUND: This study was conducted to establish an objective approach to
      evaluate symptoms and sweat production in patients with primary palmoplantar
      hyperhidrosis (PPH) and assess their response to bilateral thoracoscopic
      sympathectomy (BTS). METHODS: We conducted two institutional review board
      approved studies. We performed a one-time evaluation of healthy volunteers
      (controls) with three questionnaires (Hyperhidrosis Disease Severity Scale,
      Dermatology Life Quality Index, and Short Form-36) and measurement of
      transepidermal water loss (TEWL; g/m(2)/h). We evaluated PPH patients with these
      same tools before and 1 month after BTS and compared them with controls. RESULTS:
      We evaluated 35 controls (mean age, 23.0 +/- 3.3 years) and 45 PPH patients (mean
      age, 26.5 +/- 12.3 years); 18 PPH patients underwent BTS and the 1-month
      postoperative evaluation. Hyperhidrosis Disease Severity Scale and Dermatology
      Life Quality Index scores were higher in PPH patients than in controls (p <
      0.0001), but normalized after BTS. Short Form-36 scale scores were lower in PPH
      patients than in controls (p < 0.05), but improved significantly after BTS.
      Compared with controls, preoperative TEWL values were significantly higher in PPH
      patients (palmar: 142.7 +/- 43.6 PPH vs 115.8 +/- 48.7 controls, p = 0.011;
      plantar: 87.5 +/- 28.8 PPH vs 57.7 +/- 24.7 controls, p < 0.0001). After BTS,
      palmar TEWL values were significantly lower (49.1 +/- 29.8, p < 0.0001). Plantar
      TEWL did not change significantly (77.6 +/- 46.6, p = 0.52). CONCLUSIONS: PPH
      patients should be objectively evaluated with standardized quality of life
      measures and TEWL measurements before and after treatment. We believe that this
      objective practical approach provides a benchmark for clinical practice and
      research.

PMID- 19101311
TI  - Transapical aortic valve implantation: step by step.
AB  - PURPOSE: Transapical aortic valve implantation is a new minimally invasive
      technique for beating heart, off-pump, aortic valve implantation in high-risk
      patients. DESCRIPTION: The procedure involves antegrade aortic valve implantation
      using an oversizing technique with direct access and accurate positioning of a
      stent-based transcatheter xenograft. Procedural steps include placement of
      femoral arterial and venous access wires, anterolateral mini-thoracotomy,
      epicardial pacing, and apical pursestring suture placement. Valve positioning is
      performed under fluoroscopic and echocardiographic guidance during rapid
      ventricular pacing. EVALUATION: Patient screening, especially regarding native
      aortic annulus diameter and pattern of calcification, is essential for success.
      Since imaging is crucial, implantations are optimally performed in a hybrid
      operative theater by an experienced team of cardiac surgeons, cardiologists, and
      anesthetists. CONCLUSIONS: The aim of this article is to outline the technical
      aspects of the new technique of minimally invasive transapical aortic valve
      implantation.

PMID- 19101312
TI  - Intraoperative temperature control using the Thermogard system during off-pump
      coronary artery bypass grafting.
AB  - PURPOSE: Normothermia during off-pump coronary bypass (OPCAB) grafting reduces
      metabolic derangements and contributes to improved clinical outcomes. Thus study
      examined the feasibility and efficacy of intraoperative temperature control using
      a novel endovascular heating system during OPCAB. DESCRIPTION: Thirty-eight
      consecutive patients undergoing OPCAB were prospectively randomized to receive
      conventional warming (elevated room temperature, warmed intravenous fluids,
      warming blanket) or the Thermogard system (Alsius Corp, Irvine, CA). The triple
      lumen temperature control Icy catheter (Alsius Corp) was inserted percutaneously
      into the inferior vena cava through common femoral vein. The catheter was removed
      after all wounds were closed. Temperature measurements (bladder, nasopharyngeal,
      and blood) were recorded at 5-minute intervals and compared between groups.
      EVALUATION: Patient demographics did not significantly differ between groups. The
      17 Thermogard patients warmed at a significantly faster rate than the 21 control
      patients (0.28 degrees vs 0.11 degrees C/h, p = 0.03). Furthermore, Thermogard
      patients received more bypass grafts (3.4 +/- 0.6 vs 2.6 +/- 0.9, p < 0.001) and
      less intraoperative fluids (1557.0 +/- 547.7 vs 2012.3 +/- 723.1 mL, p = 0.02)
      despite longer operative times (150.3 +/- 123.4 vs 108.1 +/- 43.7 min; p = 0.12).
      All catheters were placed successfully on the first attempt, and there were no
      device-related complications. CONCLUSIONS: Endovascular warming is safe, simple
      to use, and obviates the need for uncomfortably warm operating room temperatures.
      The Thermogard system compared favorably with conventional methods for warming
      during OPCAB.

PMID- 19101313
TI  - Invited commentary.

PMID- 19101314
TI  - Repair of type A dissection in a Jehovah's Witness with prior cardiac operation.
AB  - As the practice of cardiothoracic surgery continues to evolve in the face of an
      aging population and increasing comorbidities, patients are being offered options
      that once may have been considered off limits, often without guidelines or
      consensus available to guide the surgeon or the patient. A case report of a high
      risk aortic procedure is presented to illustrate this conundrum.

PMID- 19101315
TI  - Aortic valve replacement for aortic regurgitation in a patient with left
      ventricular noncompaction.
AB  - We present a case of a 61-year-old man who underwent aortic valve replacement for
      aortic regurgitation complicated with left ventricular noncompaction. The
      pathogenesis of this condition remains unknown. In advanced form, left
      ventricular noncompaction produces marked disability and carries a poor
      prognosis. We underscore that familiarity with this disease entity will help to
      stimulate early diagnosis and timely treatment when necessary.

PMID- 19101316
TI  - Complete pulmonary venous occlusion after radiofrequency ablation for atrial
      fibrillation.
AB  - Pulmonary vein stenosis is a known, yet under-recognized complication of
      radiofrequency ablation for atrial fibrillation. We present the case of a patient
      developing complete left-sided pulmonary venous occlusion following
      radiofrequency ablation. Recommendations are made to allow earlier diagnosis of
      this complication.

PMID- 19101317
TI  - Pulmonary artery pseudoaneurysm after a vascular access port catheter
      implantation.
AB  - Pulmonary artery pseudoaneurysm is an unusual complication of surgically
      implantable central venous port catheters. We experienced a case of a 57-year-old
      man with gastric malignancy, in which a port catheter had been previously
      implanted for chemotherapy. Because of a puncture site that was also medial for
      the subclavian vein, the catheter tip fractured between the first rib and the
      clavicle, and embolized in the left pulmonary artery, which caused a 5 x 4 cm
      pseudoaneurysm that mandated surgical resection with a lobectomy. The diagnostic
      work-up and a review of the literature are presented.

PMID- 19101318
TI  - Resection and patch repair of a large saccular coronary artery aneurysm at the
      left main bifurcation.
AB  - Coronary artery aneurysm is a rare condition with primarily conservative
      treatment. Here, we present a case of saccular left main coronary aneurysm with a
      successful patch repair and discuss the indications for operative treatment.

PMID- 19101319
TI  - Cardiac tamponade and pulmonary embolism as a complication of percutaneous
      vertebroplasty.
AB  - Percutaneous vertebroplasty is a useful and safe therapeutic intervention to
      stabilize vertebral fractures. Rarely, cement leakage into the paravertebral
      venous system may result in embolization of its particles into the right cardiac
      chambers and pulmonary artery. We experienced a case of a 64-year-old woman who
      was diagnosed through echocardiography as having cardiac tamponade. Previously,
      the patient was treated for pulmonary cement embolization after percutaneous
      vertebroplasty. Prompt diagnosis and urgent surgery, in which a few linear cement
      particles of 1-cm to 2-cm long were discovered within the pericardial space,
      which resulted in a favorable outcome.

PMID- 19101320
TI  - Late aortic injury: a rare complication of a posterior rib fracture.
AB  - Traumatic rib fractures are common and are often associated with a hemothorax or
      pneumothorax. Rib fractures can also be a marker of severe trauma, and aortic
      transection is a well-described cause of death, particularly after a deceleration
      injury. However, direct aortic laceration by a fractured rib segment is extremely
      rare. We describe the late presentation of such a case and discuss the possible
      mechanism of injury.

PMID- 19101321
TI  - Total transvenous approach to pacing and defibrillation after Ebstein's anomaly.
AB  - We describe the successful use of a percutaneous, transvenous endocardial
      approach to atrioventricular pacing and cardiac defibrillation in an adult born
      with Ebstein's anomaly who had undergone tricuspid valve repair. The patient has
      systolic left ventricular dysfunction, congestive heart failure, and sinus node
      dysfunction. Ventricular pacing and sensing was obtained with a bipolar lead
      placed in the inferolateral cardiac vein; atrial pacing was obtained at the low
      interatrial septum. Internal cardiac defibrillation was achieved with a coil lead
      placed in the middle cardiac vein and the active can in the left retro mammary
      pre-pectoral position. With this approach, we avoided a thoracotomy and
      epicardial patch in a patient whose previous tricuspid valve surgery precluded an
      endocardial right ventricular lead position.

PMID- 19101322
TI  - Right ventricular plication in a neonate with an unguarded tricuspid valvar
      orifice.
AB  - Unguarded tricuspid orifice is a congenital cardiac malformation characterized by
      absence of the tricuspid valvar leaflets in the setting of a normal
      atrioventricular junction and obligatory severe tricuspid regurgitation. A
      neonate with such a lesion presented with severe cardiac failure. The right
      atrium and ventricle were grossly dilated, and there were small muscular
      ventricular septal defects. We plicated the right-sided structures to create
      space for adequate expansion of the lungs and left ventricular filling,
      proceeding to staged conversion to the Fontan circulation. Our experience shows
      that neonates with cardiac failure due to dilated right-sided structures can be
      stabilized by surgical plication.

PMID- 19101323
TI  - Repair of coarctation in right circumflex retroesophageal arch.
AB  - A right-sided circumflex retroesophageal aortic arch combined with a ventricular
      septal defect and severe coarctation is an extremely rare condition. Moreover,
      surgical correction is significant when performing an anatomical reconstruction
      of the left aortic arch by end-to-side and native tissue-to-tissue anastomosis
      instead of using a bypass graft. The authors describe an unusual case of a 1
      month-old neonate with a ventricular septal defect and coarctation of a right
      sided circumflex retroesophageal aortic arch who underwent successful surgical
      correction.

PMID- 19101325
TI  - Coiling of major aortopulmonary collateral arteries with agenesis of the left
      pulmonary artery prior to pneumonectomy.
AB  - The case of a patient with a left upper lobe lung tumor and unilateral agenesis
      of the left pulmonary artery with multiple aortopulmonary collaterals is
      discussed. Preoperative angiographic localization with embolization of the
      dominant multiple aortopulmonary collaterals allowed pneumonectomy to be
      performed safely with acceptable blood loss.

PMID- 19101324
TI  - Massive necrotizing pneumonia with pulmonary gangrene.
AB  - Pulmonary gangrene is an extremely rare and severe complication of pneumonia. It
      is very rarely seen in community-acquired pneumonia. A 49-year-old
      immunocompetent man was admitted with community-acquired pneumonia caused by
      Klebsiella pneumonia. His condition rapidly deteriorated with ensuing pulmonary
      gangrene and septic shock. He was successfully managed by emergency
      pneumonectomy.

PMID- 19101326
TI  - Kimura's disease presenting as the middle mediastinal mass.
AB  - Kimura's disease usually located in the periauricular area most frequently;
      however, we believe that there have been no reports about kimura's disease
      presenting as middle mediastinal mass. we describe the diagnosis and treatment of
      kimura's disease in the middle mediastinum.

PMID- 19101327
TI  - Parosteal lipoma of the rib.
AB  - Parosteal lipoma is a rare benign tumor that is composed mainly of benign mature
      lipocytes, and it has an intimate association with the underlying periosteum of
      affected bone. Parosteal lipoma involving the rib is quite rare. We believe that
      only four cases have been previously reported in the English literature. Here we
      describe an exceedingly rare case of parosteal lipoma that developed in the right
      seventh rib, which presented in a 50-year-old man having a previous history of
      trauma at this site.

PMID- 19101328
TI  - Surgical experience in a baby with congenital broncho-biliary fistula.
AB  - Congenital tracheobiliary and bronchobiliary fistulae are rare malformations in
      which patent communications exist between the respiratory system and biliary
      tract, respectively. We present a newborn who was admitted with respiratory
      distress and bilious tracheal discharge. Investigation revealed a bronchobiliary
      fistula originating from the left main bronchus, as well as biliary atresia.
      Excision of the bronchobiliary fistula was successful and the connection between
      biliary tract and gastrointestinal system was established by performance of a
      Roux-en-Y cholecysto-jejunostomy. Diagnostic tools, differential diagnosis, and
      surgical correction strategies are discussed.

PMID- 19101330
TI  - Primary cardiac synovial sarcoma with imminent tricuspid valve obstruction.

PMID- 19101329
TI  - Early bioprosthetic valve deterioration after carcinoid plaque deposition.

PMID- 19101331
TI  - Fibrosing mediastinitis associated with complete occlusion of the left main
      pulmonary artery.

PMID- 19101332
TI  - A simple method of prevention for systolic anterior motion in mitral valve repair
      by loop technique method.
AB  - The loop technique is commonly adopted as a surgical procedure in mitral valve
      repair to secure the effective valve area of the valve leaflet, and to preserve,
      as much as possible, the physiological movement of the valve leaflet or annulus.
      On the other hand, the prolapsed valve leaflet is very high in some patients. In
      this case, the redundant valve leaflet may increase the risk of development of
      postoperative systolic anterior motion because the valve leaflet is not
      surgically removed at all. In this article, we describe a simple procedure for
      preventing systolic anterior motion after mitral valve repair using the loop
      technique.

PMID- 19101333
TI  - Intracardiac calipers for artificial chordae replacement in mitral valve repair.
AB  - Length adjustment of artificial chordae is crucial in the outcome of anterior
      mitral valve repair. Herein, a simple and reproducible method of artificial
      chordal replacement using polytetrafluoroethylene suture is described. With this
      technique, the length of the neo-chordae is easily decided and the knot can be
      tied surely without change in the length using only one instrument.

PMID- 19101334
TI  - The split latissimus dorsi muscle flap to protect a bronchial stump at risk of
      bronchial insufficiency.
AB  - Consistent branching of the thoracodorsal vessels to the latissimus dorsi makes
      it possible to split the muscle into independent branched units. The use of the
      lateral split latissimus dorsi muscle flap to protect the bronchial stump in case
      of bronchus at risk of insufficiency is described.

PMID- 19101335
TI  - Biomechanics of coronary artery and bypass graft disease: potential new
      approaches.
AB  - The contribution of biomechanical factors to the incidence and distribution of
      coronary artery and bypass graft disease is underrecognized. This review examined
      the literature to determine which factors were relevant and the evidence for
      their importance. It identified two primary biomechanical factors that predispose
      to disease: (1) low-wall shear stress and (2) high-wall mechanical stress or
      strain. A range of secondary biomechanical factors have also been identified and
      include: vessel geometry; vessel movement; vessel wall characteristics and the
      presence of reflection waves. Potential surgical approaches for minimizing these
      effects are discussed.

PMID- 19101336
TI  - Clarence Crafoord: a giant in cardiothoracic surgery, the first to repair aortic
      coarctation.
AB  - On October 19, 1944, Clarence Crafoord performed the first successful repair of
      aortic coarctation. The operation was done a year before Robert Gross did his
      first case (he is often claimed to have been the first). In fact, Gross had read
      Crafoord's report before he performed his own first operation. Crafoord's
      achievement was not an isolated event. In the late 1920s he had performed two
      successful pulmonary embolectomies, in the 1930s he introduced heparin as
      thrombosis prophylaxis, and in the 1940s he pioneered mechanical positive
      pressure ventilation during thoracic operations and worked out a safe and precise
      technique for pneumonectomy. During the 1950s a string of innovative surgical
      procedures were done at his unit in Stockholm. These included the second
      successful case of cardiopulmonary bypass in the world, the first case of atrial
      repair of transposition of the great arteries, endarterectomy of the left
      coronary artery, and the first implantation of a pacemaker into a human. In this
      article we will pay tribute to Clarence Crafoord and describe some of the
      contributions that he and his collaborators made to the field of cardiothoracic
      surgery.

PMID- 19101337
TI  - Valve-in-a-valve implantation: a word of caution.

PMID- 19101339
TI  - Endovascular versus open repair for blunt thoracic aortic injury.

PMID- 19101340
TI  - Design flaws make conclusions difficult.

PMID- 19101341
TI  - Pericardial patch on coronary aneurysm.

PMID- 19101344
TI  - Minimal extracorporeal circulation: the real impact on postoperative outcome.

PMID- 19101346
TI  - Valve size does matter in the young: letter 1.

PMID- 19101347
TI  - Pannus formation in small diameter (19-21 mm) St. Jude aortic prosthesis: letter
      2.

PMID- 19101349
TI  - [Clinical complexity of psychotic disorders].

PMID- 19101350
TI  - [A decomposition of schizophrenic attention disorders].

PMID- 19101351
TI  - [Memory, memories: exploration of autobiographical memory in schizophrenia].

PMID- 19101352
TI  - [Electrophysiologic endophenotype in schizophrenia].

PMID- 19101353
TI  - [Emotional dimensions of schizophrenic disorders].

PMID- 19101354
TI  - [Clinical and therapeutic aspects of agitation].

PMID- 19101355
TI  - [Impulsivity of schizophrenic patients].

PMID- 19101356
TI  - [Insight and schizophrenic disorders].

PMID- 19101357
TI  - [Neurologic symptoms in schizophrenia].

PMID- 19101358
TI  - [Long-term management of schizophrenic disorders].

PMID- 19101359
TI  - [Compliance].

PMID- 19101360
TI  - [Neuronal plasticity of schizophrenia].

PMID- 19101362
TI  - [Electroconvulsive therapy and schizophrenia].

PMID- 19101361
TI  - [Early symptoms: vulnerability or prodrome].

PMID- 19101363
TI  - [Antipsychotic agents: what do meta analyses say?].

PMID- 19101364
TI  - Oh, what a year it was: a look back at medicine in 2008.

PMID- 19101365
TI  - Europe's health divide.

PMID- 19101366
TI  - Preventing and controlling healthcare-associated infections.

PMID- 19101367
TI  - Multiple courses of antenatal corticosteroids.

PMID- 19101368
TI  - Creationism--remember the principle of falsifiability.

PMID- 19101369
TI  - Voting opens for paper of the year 2008.

PMID- 19101370
TI  - Call for papers: surgical research--Act 2, answers?

PMID- 19101372
TI  - Werner Hacke: a pioneer in stroke care.

PMID- 19101373
TI  - Martin Birchall: using stem cells to help make transplant history.

PMID- 19101374
TI  - Christos Karapetis: making a difference with oncology trials.

PMID- 19101375
TI  - Abdullah Baqui: saving newborn lives in Bangladesh and globally.

PMID- 19101376
TI  - George Daley: individualising stem-cell research.

PMID- 19101377
TI  - Zhong Nan-Shan: leader of clinical research in China.

PMID- 19101378
TI  - Research and the issue of patients' consent.

PMID- 19101379
TI  - Epidural analgesia and postoperative outcome.

PMID- 19101380
TI  - Epidural analgesia and postoperative outcome.

PMID- 19101382
TI  - Cognitive behaviour therapy for depressed Pakistani mothers.

PMID- 19101384
TI  - Cognitive behaviour therapy for depressed Pakistani mothers.

PMID- 19101386
TI  - Influenza vaccination and risk of community-acquired pneumonia.

PMID- 19101387
TI  - Ivabradine in heart failure: what about digoxin?

PMID- 19101389
TI  - The new Access to Medicine Index.

PMID- 19101391
TI  - De testimonio: on the evidence for decisions about the use of therapeutic
      interventions.

PMID- 19101392
TI  - Always on call.

PMID- 19101393
TI  - Dangerous sandwiches.

PMID- 19101394
TI  - Quiz page. Congenital intrathoracic kidney after regression of an adrenal mass.

PMID- 19101395
TI  - Kidney injury molecule 1: in search of biomarkers of chronic tubulointerstitial
      damage and disease progression.

PMID- 19101396
TI  - IgA nephropathy: a disease in search of a large-scale clinical trial to reliably
      inform practice.

PMID- 19101390
TI  - Multiple courses of antenatal corticosteroids for preterm birth (MACS): a
      randomised controlled trial.
AB  - BACKGROUND: One course of antenatal corticosteroids reduces the risk of
      respiratory distress syndrome and neonatal death. Weekly doses given to women who
      remain undelivered after a single course may have benefits (less respiratory
      morbidity) or cause harm (reduced growth in utero). We aimed to find out whether
      multiple courses of antenatal corticosteroids would reduce neonatal morbidity and
      mortality without adversely affecting fetal growth. METHODS: 1858 women at 25-32
      weeks' gestation who remained undelivered 14-21 days after an initial course of
      antenatal corticosteroids and continued to be at high risk of preterm birth were
      randomly assigned to multiple courses of antenatal corticosteroids (n=937) or
      placebo (n=921), every 14 days until week 33 or delivery, whichever came first.
      The primary outcome was a composite of perinatal or neonatal mortality, severe
      respiratory distress syndrome, intraventricular haemorrhage (grade III or IV),
      periventricular leucomalacia, bronchopulmonary dysplasia, or necrotising
      enterocolitis. Analysis was by intention to treat. All patients and caregivers
      were unaware of the treatment given. This trial is registered as number
      ISRCTN2654148. FINDINGS: Infants exposed to multiple courses of antenatal
      corticosteroids had similar morbidity and mortality to those exposed to placebo
      (150 [12.9%] vs 143 [12.5%]). Those receiving multiple doses of corticosteroids
      also weighed less at birth than those exposed to placebo (2216 g vs 2330 g,
      p=0.0026), were shorter (44.5 cm vs 45.4 cm, p<0.001), and had a smaller head
      circumference (31.1 cm vs 31.7 cm, p<0.001). INTERPRETATION: Multiple courses of
      antenatal corticosteroids, every 14 days, do not improve preterm-birth outcomes,
      and are associated with a decreased weight, length, and head circumference at
      birth. Therefore, this treatment schedule is not recommended. FUNDING: Canadian
      Institutes of Health Research.

PMID- 19101397
TI  - Blood pressure and mortality risk in patients treated by peritoneal dialysis.

PMID- 19101398
TI  - More is not always better: intensive glycemic control in type 2 diabetes.

PMID- 19101400
TI  - CKD and poverty: a growing global challenge.
AB  - Approximately 1.2 billion individuals worldwide live in extreme poverty (< $1/d),
      and 2.7 billion live in moderate poverty (< $2/d). Poverty is most prevalent in
      developing countries, but does not spare richer economies, where huge income
      discrepancies have been reported. Poverty is a major health care marker affecting
      a number of chronic, communicable, and noncommunicable diseases. Poverty and
      social deprivation are known to affect the predisposition, diagnosis, and
      management of chronic diseases; they directly impact on the prevalence of such
      conditions as obesity, diabetes, and hypertension. Also, growing evidence links
      poverty to chronic kidney disease (CKD). This may be caused by a direct impact of
      poverty on CKD or indirectly through the increased health care burden linked to
      poverty-associated diabetes and hypertension. Furthermore, data have shown that
      the poor and socially deprived have a greater prevalence of end-stage renal
      disease. Access to renal care, dialysis, and transplantation may also be affected
      by social deprivation. Overall, poverty and social deprivation are emerging as
      major risk markers for CKD in both developing and developed countries. Their
      impact on CKD warrants careful analysis because it may confound the
      interpretation of CKD risk factors within communities. This review therefore aims
      to look at the evidence linking poverty to CKD and its major risk factors,
      namely, diabetes and hypertension.

PMID- 19101401
TI  - Urinary albumin-total protein ratio: a new diagnostic tool to differentiate
      glomerular from nonglomerular hematuria?

PMID- 19101399
TI  - Obesity management in adults with CKD.

PMID- 19101402
TI  - Introduction: Advances in treatment of metastatic colorectal cancer.

PMID- 19101403
TI  - Sequential or combination chemotherapy for a patient with mCRC?
AB  - A 62-year-old male presents with colon cancer that has metastasized to both lobes
      of the liver. Resection was performed; chemotherapy initially consisted of
      combination treatment with FOLFIRI or XELIRI plus bevacizumab, with the
      possibility of changing treatment to either FU/LV or capecitabine, combined with
      bevacizumab. Although reported data would allow the consideration of a strategy
      of sequential treatment in this patient, the consulting oncologists treating him
      have acknowledged the benefit of a strategy employing "inductive" combination
      chemotherapy plus monoclonal antibodies. Combination chemotherapy offers the
      potential for longer treatment holidays than is possible with sequential therapy.
      One of the enduring concepts informing treatment decisions for mCRC is that
      patients who receive the three mainstays of drug treatment fluorouracil,
      irinotecan, and oxaliplatin fare better than those who do not.

PMID- 19101404
TI  - A dilemma in geriatric oncology: malignant bowel obstruction in an 81-year-old
      man.
AB  - An 81-year-old male presenting with bowel obstruction was found upon examination
      to have bilobar liver metastases. In light of the patient's advanced age, bowel
      resection was foregone in favor of stent deployment, which led to rapid
      resolution of symptoms. The multidisciplinary team assembled to coordinate
      further care advised the use of chemotherapy with irinotecan, oxaliplatin, and 5
      FU, which was well tolerated and led to an objective response. The special
      considerations relevant to the patient's advanced age, including the choice of
      stent deployment rather than resection and the decision to employ 5-FU-based
      chemotherapy in spite of limited trial data with this approach in patients of
      advanced age, are explained in detail.

PMID- 19101405
TI  - First-line combination treatment of colorectal cancer with hepatic metastases:
      choosing a targeted agent.
AB  - A 56-year-old man has a history of bright red blood per rectum for 3 months;
      computed tomography reveals 4 hepatic lesions in the right lobe, the largest
      measuring 5.5 cm. Chemotherapy may accomplish sufficient reduction of the hepatic
      tumor burden to enable surgery with curative intent. Both FOLFOX and FOLFIRI are
      appropriate, highly active first- line regimens that may also be administered as
      second-line salvage chemotherapy. Research continues to evaluate the safety and
      efficacy of combining bevacizumab and cetuximab or adding them singly to
      established chemotherapy regimens. In patients with initially unresectable
      tumors, a direct relationship of response to chemotherapy with attainment of
      resectability supports a strategy of using the most active regimens in
      potentially curable patients. Literature confirms the importance of exposing
      patients to the most efficacious agents during the course of disease treatment.
      Genetic testing for specific mutations such as KRAS may be helpful for supporting
      a treatment decision to use cetuximab.

PMID- 19101406
TI  - Recurrent disease four years after surgery and adjuvant chemotherapy.
AB  - A 71-year-old man with previous primary resection was found to have extensive
      liver metastases. Chemotherapy was initiated with FOLFIRI plus bevacizumab, in
      hopes of reducing the hepatic tumor burden; this resulted in manageable toxicity
      and was sufficiently effective to allow resection. After 6 weeks, 6 cycles of
      chemotherapy with FOLFIRI plus bevacizumab were administered; the patient was
      free of new lesions for the next 19 months. Readministration of FOLFIRI plus
      bevacizumab resulted in minor response and symptom control for another 9 months
      before further progression was observed. The subsequent administration of FOLFOX
      for 8 cycles and FOLFIRI plus cetuximab were unable to prevent further decline.
      Detailed explanation of the selection of appropriate surgical and
      chemotherapeutic options are provided throughout the case discussion.

PMID- 19101408
TI  - Syringe or pump for air-assisted DSAEK.

PMID- 19101409
TI  - Complications of CTR implantation in pediatric eyes.

PMID- 19101413
TI  - Consultation section: refractive surgical problem.

PMID- 19101412
TI  - Diagnosis of post-LASIK occult Chandler syndrome.

PMID- 19101418
TI  - Femtosecond-assisted astigmatic keratotomy for post-keratoplasty irregular
      astigmatism.
AB  - We describe the technique of femtosecond-assisted astigmatic keratotomy (AK) in a
      post-keratoplasty patient with irregular, nonorthogonal astigmatism. Using the
      keratoplasty software, an anterior arcuate side cut (400 mum thick, 6.5 mm
      diameter) was created using the femtosecond laser in a 68-year-old woman with
      irregular astigmatism 28 years after penetrating keratoplasty for keratoconus. No
      intraoperative or postoperative adverse events were seen during the follow-up
      period. Six months after the procedure, the uncorrected visual acuity improved
      from 20/60 to 20/50 and the best spectacle-corrected visual acuity, from 20/50 to
      20/32. The mean manifest astigmatic correction decreased from 4.00 diopters (D)
      to 0.50 D; corneal topography showed a significant improvement in irregular
      astigmatism. The technique of femtosecond-assisted AK is simple and efficient for
      managing irregular and nonorthogonal astigmatism in post-keratoplasty patients
      and may overcome the limitations of earlier techniques.

PMID- 19101419
TI  - Quantification of glistenings in intraocular lenses using Scheimpflug
      photography.
AB  - We describe a method of quantifying glistenings in intraocular lenses (IOLs)
      using Scheimpflug photography. Glistenings in hydrophilic acrylic IOLs implanted
      over a 10-year period were quantified subjectively at the slitlamp and by digital
      image analysis of Scheimpflug photographs; the latter involved analysis of
      glistenings in the anterior and posterior IOL surfaces. Glistenings were seen in
      all IOLs, with more in those with a longer postoperative period. This association
      was stronger with Scheimpflug quantification (r(S) = 0.70; P<.000) than with
      subjective quantification (r(S) = 0.32; P = .11). Anterior and posterior IOL
      glistenings developed similarly over time. Scheimpflug photography had a higher
      degree of objectivity than subjective staging of IOL glistenings and also
      provided information about the axial localization of the glistenings. This
      investigation indicated that IOL glistenings continued to increase for up to 10
      years.

PMID- 19101420
TI  - Role of combined cataract surgery and intravitreal bevacizumab injection in
      preventing progression of diabetic retinopathy: prospective randomized study.
AB  - PURPOSE: To evaluate the role of intravitreal bevacizumab, an anti-vascular
      endothelial growth factor agent, injected at the time of cataract surgery on the
      postoperative progression of diabetic retinopathy (DR) and diabetic maculopathy.
      SETTING: Tertiary-care eye specialty hospital, Dhahran, Kingdom of Saudi Arabia.
      METHODS: Patients were randomized to a standardized procedure of
      phacoemulsification with intraocular lens implantation alone (control group) or
      to receive 1.25 mg intravitreal bevacizumab at the end of surgery (intervention
      group). Diabetic retinopathy and maculopathy were assessed at each postoperative
      visit during a 6-month follow-up. RESULTS: Sixty-eight eyes (68 patients) with DR
      and cataract were recruited for this prospective study. Progression of DR
      occurred in 15 (45.45%) of 33 eyes in the control group and 4 (11.42%) of 35 eyes
      in the intervention group (P = .002) Progression of diabetic maculopathy occurred
      in 17 eyes (51.51%) in the control group and 2 eyes (5.71%) in the intervention
      group (P = .0001). There was no statistically significant difference in
      postoperative visual acuity between the 2 groups (P = .772). Two eyes in the
      control group and none in the intervention group progressed to neovascular
      glaucoma. The mean postoperative central macular thickness and mean macular
      thickness were not statistically significantly different between the 2 groups (P
      = .874 and .942, respectively). CONCLUSION: Intravitreal administration of 1.25
      mg bevacizumab at the time of cataract surgery was safe and effective in
      preventing the progression of DR and diabetic maculopathy in patients with
      cataract and DR.

PMID- 19101421
TI  - Difluprednate ophthalmic emulsion 0.05% for postoperative inflammation and pain.
AB  - PURPOSE: To assess the efficacy and safety of difluprednate ophthalmic emulsion
      0.05% (Durezol) 2 or 4 times a day compared with those of a placebo in the
      treatment of inflammation and pain associated with ocular surgery. SETTING:
      Twenty-six clinics in the United States. METHODS: One day after unilateral ocular
      surgery, patients who had an anterior chamber cell grade of 2 or higher (>10
      cells) were treated with 1 drop of difluprednate 2 times or 4 times a day or with
      a placebo (vehicle) 2 times or 4 times a day in the study eye for 14 days. This
      was followed by a 14-day tapering period and a 7-day safety evaluation. Outcome
      measures included cleared anterior chamber inflammation (grade 0, <or=1 cell),
      absence of pain, and analysis of ocular adverse events. RESULTS: Of the 438
      patients, 111 received difluprednate 2 times a day, 107 received difluprednate 4
      times a day, and 220 received a placebo 2 or 4 times a day. Both difluprednate
      dosage regimens reduced postoperative ocular inflammation and pain safely and
      effectively compared with the placebo. A greater proportion of difluprednate
      treated patients had a reduction in inflammation and pain at 8 days and 15 days.
      Three percent of patients in both difluprednate groups had a clinically
      significant IOP rise (>or=10 mm Hg and >or=21 mm Hg from baseline, respectively)
      versus 1% in the placebo group. CONCLUSIONS: Difluprednate given 2 or 4 times a
      day cleared postoperative inflammation and reduced pain rapidly and effectively.
      There were no serious ocular adverse events. Fewer adverse events were reported
      in the difluprednate-treated groups than in the placebo group.

PMID- 19101422
TI  - Corneal architecture of femtosecond laser and microkeratome flaps imaged by
      anterior segment optical coherence tomography.
AB  - PURPOSE: To assess and compare the morphology of laser in situ keratomileusis
      flaps (LASIK) created by a 60 kHz femtosecond laser and a mechanical
      microkeratome. SETTING: Department of Ophthalmology, Johann Wolfgang Goethe
      University, Frankfurt am Main, Germany. METHODS: Anterior segment optical
      coherence tomography (AS-OCT) (Visante) was used to assess 1 week postoperatively
      the morphology of 20 LASIK flaps created with the IntraLase femtosecond laser or
      the Zyoptix XP microkeratome. The flap diameter and flap thickness were assessed
      at 20 measuring points across each flap. First, the repeatability of the AS-OCT
      flap measurement was evaluated. On this basis, the dimensions of femtosecond
      laser flaps and microkeratome flaps were tested and their regularity,
      reproducibility, and accuracy compared. RESULTS: The method was approved with a
      repeatability of maximum 8.9 mum. The femtosecond laser flaps were more regular
      than the microkeratome flaps (P = .02). The reproducibility of flap morphology
      was not different in the central 1.0 mm radius area (P = .26); however, the
      femtosecond laser was significantly more precise than the microkeratome in the
      peripheral area (P = .001). The mean thickness of the femtosecond laser flap was
      significantly more accurate than the mean thickness of the microkeratome flap (P
      = .01), with a mean deviation of +16.9 mum and 40.8 mum, respectively.
      CONCLUSIONS: The flap architecture created with the femtosecond laser was more
      regular and accurate than the flap architecture created with the microkeratome.

PMID- 19101423
TI  - Aceclidine, brimonidine tartrate, and dapiprazole: comparison of miotic effect
      and tolerability under different lighting conditions.
AB  - PURPOSE: To evaluate the effect of 3 types of topically applied miotic eyedrops
      on the pupil diameter in normal eyes. SETTING: Department of Neurosciences,
      Section of Ophthalmology, University of Pisa, Pisa, Italy. METHODS: This
      prospective study comprised 60 eyes of 30 healthy volunteers treated with
      aceclidine 0.02%, brimonidine tartrate 0.20%, and dapiprazole 0.25%. Pupil
      diameter was measured under scotopic, mesopic (4 lux), and photopic (50 lux)
      conditions using an infrared pupillometer incorporated into a CSO topographer.
      The first measurement was obtained before single instillation of 1 type of miotic
      eyedrop. Subsequent measurements were taken after 30, 120, and 240 minutes. Each
      additional medication was tested after an interval of at least 6 weeks to avoid
      possible effects from the previously administered drug. All patients received a
      questionnaire and were asked to grade the tolerability of each eyedrop using a
      subjective scoring system. RESULTS: Aceclidine 0.02% had no significant miotic
      effect. Brimonidine tartrate 0.20% caused significant miosis within 30 minutes
      and 120 minutes; after 240 minutes, the effect under all luminance conditions
      decreased to baseline levels without reaching the initial level. Dapiprazole
      0.25% had a miotic effect similar to that of brimonidine but produced many side
      effects including hyperemia and burning, which many patients said caused
      significant discomfort. CONCLUSIONS: Brimonidine tartrate 0.20% had the best
      miotic effect of the 3 agents tested and was well tolerated by the patients. The
      reproducible miotic effect of brimonidine tartrate under all lighting conditions
      might benefit postoperative refractive patients who report night-vision
      difficulties related to large pupils.

PMID- 19101424
TI  - Relationship between contrast sensitivity and spherical aberration: comparison of
      7 contrast sensitivity tests with natural and artificial pupils in healthy eyes.
AB  - PURPOSE: To find a contrast sensitivity test that can be used clinically to
      evaluate interventions aimed at minimizing spherical aberration and determine the
      circumstances under which these tests should be performed. SETTING: Laboratory of
      Experimental Ophthalmology, University of Groningen, Groningen, The Netherlands.
      METHODS: Contrast sensitivity tests were performed using 2 experimental designs.
      Design 1 was with a natural pupil under mesopic and photopic conditions. Design 2
      was with a 5.0 mm artificial pupil after cycloplegia under photopic conditions
      only. Two computerized tests (vertical sine-modulated gratings [VSG] and Holladay
      circular sine-modulated patterns [HACSS]) and 5 chart tests (Pelli-Robson, acuity
      measuring letter charts at low contrast [2.5% and 10%], VectorVision, and edge
      contrast sensitivity) were used. Spherical aberration was assessed with a
      Hartmann-Shack wavefront analyzer. RESULTS: Forty-nine healthy subjects aged 20
      to 35 years (n = 24) and 55 to 70 years (n = 25) participated. Design 2 showed a
      significant relationship between contrast sensitivity and spherical aberration
      with the HACSS at 3 cycles per degree (cpd) (P = .03) and 6 cpd (P = .01) and
      with the VSG at 6 cpd (P = .01). Design 1 yielded no significant relationships.
      CONCLUSIONS: Using an artificial pupil, a relationship between contrast
      sensitivity and spherical aberration was established with the VSG and HACSS tests
      but not with the chart tests. No test showed a relationship using natural pupils
      under either lighting condition. Chart tests are unsuitable for uncovering
      contrast sensitivity differences related to differences in spherical aberration,
      as typically found in healthy phakic eyes.

PMID- 19101425
TI  - Effect of spherical aberration on visual function under photopic and mesopic
      conditions after cataract surgery.
AB  - PURPOSE: To evaluate the effect of spherical aberration on visual function under
      natural pupil conditions after cataract surgery. SETTING: Keio University
      Hospital, Tokyo, Japan. METHODS: This study comprised cataract patients who had
      cataract extraction with implantation of an acrylic intraocular lens.
      Preoperative and postoperative visual acuity, higher-order aberration in the
      whole eye, contrast sensitivity function, and pupil diameter under photopic and
      mesopic conditions 1 month after surgery were measured. The area under log
      contrast sensitivity function (AULCSF) and spherical aberration corresponding to
      the individual pupil diameter under photopic and mesopic conditions were
      evaluated. RESULTS: One hundred seven eyes of 79 patients (30 men, 49 women; mean
      age 68.0 years +/- 9.6 [SD]) were evaluated. The mean pupil diameter was 2.9 +/-
      0.50 mm under photopic conditions and 3.6 +/- 0.57 mm under mesopic conditions.
      The mean spherical aberration was 0.03 +/- 0.04 mum (range -0.12 to 0.34 mum)
      under photopic conditions and 0.05 +/- 0.10 mum (range -0.14 to 0.55 mum) under
      mesopic conditions. The postoperative AULCSF without glare under photopic
      conditions was significantly negatively correlated with spherical aberration (P =
      .014). The postoperative AULCSF with and without glare under mesopic conditions
      was significantly negatively correlated with spherical aberration (P<.001 and P =
      .01, respectively). CONCLUSIONS: Postoperative spherical aberration had a
      significant effect on visual function under photopic and mesopic conditions. This
      result indicates that reduced postoperative spherical aberration improves
      postoperative visual function under photopic and mesopic conditions.

PMID- 19101426
TI  - Optical biometry in combined phacovitrectomy.
AB  - PURPOSE: To assess the accuracy of intraocular lens (IOL) power calculation using
      optical biometry in patients having combined phacovitrectomy for macular hole and
      macular pucker. SETTING: Sunderland Eye Infirmary, North East England, United
      Kingdom. METHODS: This single-surgeon retrospective case series review comprised
      eyes having combined narrow-gauge phacovitrectomy for macular hole or macular
      pucker. Intraocular lens power was calculated using the results of optical
      biometry and the Haigis formula. Achieved and planned refraction were compared to
      calculate the mean postoperative refractive prediction error (ME) and the mean
      absolute postoperative prediction error (MAE) and the percentage of eyes with an
      achieved refraction within +/-0.50 diopter (D) and +/-1.00 D of the planned
      refraction. The results were compared with those in a series of 42 eyes that had
      phacoemulsification after previous vitrectomy surgery and a series of 60
      nonvitrectomized eyes that had uneventful phacoemulsification. RESULTS: Of the of
      59 having combined phacovitrectomy, 39 had macular hole and 20 had macular
      pucker. There was no statistically significant difference in refractive outcomes
      between the phacovitrectomy group (ME -0.02, MAE 0.39) and the sequential
      phacoemulsification group (ME -0.10, MAE 0.38) (P = .82). There was a
      statistically significant difference between the phacovitrectomy group and the
      phacoemulsification-only group (ME 0.08, MAE 0.26) (P<.001). CONCLUSIONS: The use
      of optical noncontact biometry with the Haigis formula achieved a high degree of
      accuracy of IOL power estimation in patients having phacovitrectomy. There was no
      tendency toward a myopic shift, as has been reported using ultrasound axial
      length measurement.

PMID- 19101427
TI  - Prevalence of corneal astigmatism before cataract surgery.
AB  - PURPOSE: To analyze the prevalence and presentation patterns of corneal
      astigmatism in cataract surgery candidates. SETTING: University of Valencia,
      Valencia, Spain. METHODS: Refractive and keratometric values were measured before
      surgery in patients having cataract extraction. Descriptive statistics of
      refractive and keratometric cylinder data were analyzed and correlated by age
      ranges. RESULTS: Refractive and keratometric data from 4,540 eyes of 2,415
      patients (mean age 60.59 years +/- 9.87 [SD]; range 32 to 87 years) differed
      significantly when the patients were divided into 10-year subsets. There was a
      trend toward less negative corneal astigmatism values, except the steepest
      corneal radius and the J(45) vector component, in older groups (Kruskal-Wallis,
      P<.01). In 13.2% of eyes, no corneal astigmatism was present; in 64.4%, corneal
      astigmatism was between 0.25 and 1.25 diopters (D) and in 22.2%, it was 1.50 D or
      higher. CONCLUSIONS: Corneal astigmatism less than 1.25 D was present in most
      cataract surgery candidates; it was higher in about 22%, with slight differences
      between the various age ranges. This information is useful for intraocular lens
      (IOL) manufacturers to evaluate which age ranges concentrate the parameters most
      frequently needed in sphere and cylinder powers and for surgeons to evaluate
      which IOLs provide the most effective power range.

PMID- 19101428
TI  - Intraocular pressure assessment in both eyes of the same patient after laser in
      situ keratomileusis.
AB  - PURPOSE: To measure intraocular pressure (IOP) after laser in situ keratomileusis
      (LASIK) in both eyes of the same patient and analyze the correlation between IOP
      measurement and keratometric (K) power, central corneal thickness (CCT), and
      laser ablation depth. SETTING: Private practice, Kaohsiung, Taiwan. METHODS: This
      prospective cohort study enrolled patients with myopia or myopic astigmatism. In
      all patients, the targeted post-LASIK spherical equivalent was within +/-0.25
      diopter. The IOP was measured using noncontact tonometry; K power, by
      autokeratorefractometry; and CCT, by ultrasound pachymetry. Laser ablation depth
      was determined using the excimer laser's software, and the ratio of laser
      ablation depth to decreased IOP was calculated. Correlations were determined by
      stepwise multiple regression analysis and the Mann-Whitney U test. RESULTS: High
      preoperative IOP was significantly associated with high postoperative IOP
      (P<.001) and with a large decrease in IOP (P<.001). Thus, 62.7% and 37.5% of
      postoperative IOP and decreased IOP measurements, respectively, were explainable
      by the preoperative IOP. Postoperative IOP (P = .904), decreased IOP after LASIK
      (P = .479), and the ratio of laser ablation depth to decreased IOP (P = .971) did
      not significantly differ and were positively correlated (P<.001) between eyes of
      the same patient. CONCLUSIONS: The IOP measurement reduction after LASIK was
      greater in cases of higher preoperative IOP and smaller in cases of lower
      preoperative IOP. The IOP measurements after LASIK were not significantly
      associated with laser ablation depth, and the measurements were similar and
      proportional in eyes of the same patient.

PMID- 19101429
TI  - Effect of a blue-light-blocking intraocular lens on the quality of sleep.
AB  - PURPOSE: To evaluate whether implantation of a blue-light-blocking intraocular
      lens (IOL) affects sleep quality. SETTING: Repatriation General Hospital,
      Adelaide, Australia. METHODS: This study comprised patients who had bilateral
      cataract surgery during the preceding 12 months with implantation of a
      conventional SI40NB IOL or an AcrySof Natural SN60WF blue-light-blocking IOL.
      Patients were contacted by telephone at least 6 months after second-eye surgery,
      and the Pittsburgh Sleep Quality Index (PSQI) questionnaire was administered.
      Results were compared between groups. RESULTS: Of the 49 patients, 31 received
      conventional IOLs and 18, blue-light-blocking IOLs. The mean age of the patients
      was 80 years +/- 8.1 (SD). The median PSQI score was 6 (interquartile range 3 to
      8). There were no statistically significant differences in PSQI scores between
      the 2 IOL groups (P = .65). This remained true after adjustment for sex, age,
      medication, and time since surgery. CONCLUSION: The blue-light-blocking IOL had
      no effect on the sleep quality of patients, indicating that these IOLs might
      serve as an alternative to conventional IOLs without a detrimental effect on
      circadian rhythm.

PMID- 19101430
TI  - Postcataract acute endophthalmitis in France: national prospective survey.
AB  - PURPOSE: To report results of the National French Observational Database for
      Endophthalmitis (Observatoire National Des Endophtalmies [ONDE]). SETTING:
      Departments of ophthalmology at universities, general hospitals, and private
      clinics. METHODS: In this multicenter national interventional case series, data
      were collected prospectively between March 1, 2003, and November 1, 2004, from
      French ophthalmologists who answered a standardized 175-item questionnaire. The
      data were from patients with acute-onset endophthalmitis after cataract surgery.
      Before surgery, all 105 patients had received an official information card from
      the French Ophthalmological Society and provided written informed consent.
      RESULTS: The study comprised 105 patients. The median time from cataract
      extraction to endophthalmitis was 4 days (range 1 to 39 days). All but 1 patient
      had symptoms, with blurred vision being the most common. Initial visual acuity
      was 5/200 or better in 18.9% (18/95) of patients. Intraocular samples from 90.5%
      (95/105) of patients yielded 45 pathogens, of which 86.7% were gram positive.
      Treatments included intraocular antibiotic injections in 95.1% (98/103) of
      patients, intraocular steroid injections in 41.4% (41/99) of patients, and
      immediate vitrectomy in 14.0% (14/100) of patients. Visual acuity at 3 months was
      20/100 in 64% of patients. CONCLUSIONS: The ONDE study disclosed important
      changes in French ophthalmic surgical practice 15 years after the first
      prospective endophthalmitis survey and 12 years after a United States study were
      published. Progress toward standardization of preventive methods (eg, patient
      information, increased systemic antibiotic efficacy, more frequent corticosteroid
      use) has contributed to fewer vitrectomies.

PMID- 19101431
TI  - Laser flare photometry in the therapeutic management of bacterial chronic
      pseudophakic endophthalmitis.
AB  - PURPOSE: To evaluate laser flare photometry in measuring aqueous humor
      inflammation in chronic pseudophakic endophthalmitis. SETTING: Department of
      Ophthalmology, Pitie Salpetriere Hospital, Paris, France. METHODS: This
      retrospective review comprised eyes with chronic pseudophakic endophthalmitis
      that were evaluated by slitlamp and laser flare photometry at admission and
      during follow-up. RESULTS: Nine eyes of 8 patients were reviewed. The laser flare
      photometry values were significantly reduced by antibiotic treatment in all eyes.
      The laser flare photometry values increased after antibiotic treatment was
      withdrawn in 7 eyes. Early detection of the relapse by laser flare photometry was
      confirmed at the slitlamp examination in the following days. CONCLUSIONS: Laser
      flare photometry, a noninvasive objective tool, was useful in monitoring the
      evolution of chronic pseudophakic endophthalmitis. Early detection of an increase
      in flare could lead to a close follow-up. The prompt modification of therapeutic
      intervention could help preserve a favorable visual outcome.

PMID- 19101432
TI  - Excimer laser-assisted lamellar keratoplasty for the surgical treatment of
      keratoconus.
AB  - PURPOSE: To evaluate the anatomical and functional results of excimer laser
      assisted lamellar keratoplasty (ELLK) in keratoconus patients. SETTING: Eye
      Clinic, University of L'Aquila, L'Aquila, Italy. METHODS: This prospective case
      series comprised patients with keratoconus who had ELLK and were examined
      preoperatively and 3, 6, 12, and 24 months postoperatively. Outcome measures were
      uncorrected visual acuity (UCVA), best spectacle-corrected visual acuity (BSCVA),
      refraction, computerized videokeratography, pachymetry, and endothelial specular
      microscopy. RESULTS: Forty-one eyes (41 patients) were examined. The UCVA and
      BSCVA were significantly better at all follow-up examinations than
      preoperatively. After the 24-month follow-up (33 patients), the UCVA was better
      than 20/60 in 11 patients (33.3%) and the BSCVA was 20/40 or better in 29
      patients (87.9%). The mean refractive astigmatism was 2.20 diopters (D) and the
      mean manifest refraction spherical equivalent refraction, -1.18 D. Corneal
      topographic patterns were regularly astigmatic in 28 (84.8%) of 33 eyes, and the
      mean corneal thickness (440.0 mum) was significantly greater than preoperatively
      (553.0 mum). No statistically significant changes in mean corneal endothelial
      cell density were observed postoperatively. Complications included corneal
      melting treated with penetrating keratoplasty (PKP) (1 case) and postoperative
      high refractive error requiring topographically guided excimer laser
      photorefractive keratectomy (7 cases). CONCLUSIONS: Two-year findings indicate
      that ELLK is as efficacious as PKP for the surgical treatment of moderate to
      advanced keratoconus. The procedure is relatively simple. Most steps can be
      standardized, and there are no time-consuming maneuvers.

PMID- 19101433
TI  - Intraobserver and interobserver repeatability of curvature and aberrometric
      measurements of the posterior corneal surface in normal eyes using Scheimpflug
      photography.
AB  - PURPOSE: To assess the intraobserver and interobserver repeatability of curvature
      and aberrometric measurements of the posterior corneal surface provided by a
      Scheimpflug photography system in normal eyes. SETTING: Vissum-Instituto de
      Oftalmologico de Alicante, Alicante, Spain. METHODS: All eyes received a
      comprehensive ophthalmologic examination including corneal topographic analysis
      with a Scheimpflug photography system (Pentacam). Three repeated consecutive
      measurements were taken by 2 independent experienced examiners to assess
      intraobserver and interobserver repeatability for posterior corneal surface
      measurements. Keratometry, astigmatism, best-fit sphere (BFS), asphericity (Q),
      and aberrometry (6.0 mm pupil diameter) were analyzed. Precision, repeatability,
      and intraclass correlation coefficients were calculated for evaluating
      intraobserver repeatability. Bland-Altman analysis was used for assessing
      interobserver repeatability. RESULTS: Twenty eyes (20 patients) were included.
      Patients ranged in age from 21 to 50 years. The best intraobserver precision
      values were for BFS and Q in the central 8.0 mm (0.037 mm and 0.05,
      respectively). For both observers, intraobserver precision and repeatability
      achieved an acceptable level for keratometric readings (precision <0.09 diopter).
      The most limited intraobserver precision was for Q in the central 6.0 mm (0.117
      observer 1; 0.099 observer 2). Interobserver ranges of agreement were not
      clinically relevant for any parameter except Q in the central 6.0 mm (0.116).
      Regarding aberrometry, intraobserver repeatability and interobserver
      repeatability were acceptable only for primary and secondary spherical
      aberration. CONCLUSION: The Pentacam system provided reliable measurements of
      corneal posterior keratometry, astigmatism, and asphericity for large diameters
      of analysis. However, poor repeatability was observed for aberrometric
      measurements.

PMID- 19101434
TI  - Results of cataract surgery after implantation of an iris-fixated phakic
      intraocular lens.
AB  - PURPOSE: To report the results of cataract surgery after previous implantation of
      an Artisan iris-fixated phakic intraocular lens (pIOL) for the correction of
      myopia. SETTING: University center and private practice. METHODS: This study
      comprised eyes with previous implantation of an iris-fixated pIOL to correct
      myopia and subsequent pIOL explantation combined with cataract surgery and in-the
      bag implantation of a posterior chamber IOL. Predictability of refractive
      results, changes in endothelial cell density (ECD), and postoperative best
      corrected visual acuity (BCVA) were analyzed. RESULTS: The mean follow-up after
      cataract surgery in the 36 eyes of 27 consecutive patients was 5.7 months +/- 7.5
      (SD). The mean time between pIOL implantation and cataract surgery was 5.0 +/-
      3.4 years. After explantation of the pIOL and subsequent cataract surgery, the
      mean spherical equivalent (SE) was -0.28 +/- 1.11 diopters (D); the SE was within
      +/-1.00 D of the intended correction in 72.2% of patients and within +/-2.00 D in
      86.1% of patients. The mean endothelial cell loss after the combined procedure
      was 3.5% +/- 13.2% and the mean postoperative BCVA, 0.17 +/- 0.18 logMAR.
      CONCLUSIONS: In patients with a history of implantation of an iris-claw pIOL for
      the correction of myopia, cataract surgery combined with explantation of the pIOL
      yielded acceptable predictability of the postoperative SE and minimal loss of
      ECD, resulting in a gain in BCVA.

PMID- 19101435
TI  - Repeatability, reproducibility, and agreement characteristics of rotating
      Scheimpflug photography and scanning-slit corneal topography for corneal power
      measurement.
AB  - PURPOSE: To evaluate the repeatability, reproducibility, and agreement in
      anterior, posterior, and in particular the total corneal power of 2 topography
      devices, rotating Scheimpflug photography and scanning-slit topography. SETTING:
      Department of Ophthalmology and Visual Science, Kitasato University Graduate
      School of Medical Sciences, Sagamihara, Japan. METHODS: Seventeen eyes of 17
      subjects (mean age 24.7 years +/- 4.1 [SD]) were included in the study. The
      corneal shapes within the central 3.0 mm were measured with rotating Scheimpflug
      photography (Pentacam) and scanning-slit corneal topography (Orbscan II). The
      within-rater repeatability and reproducibility of 2 raters and the overall
      between-instrument agreement of the measurements were evaluated using intraclass
      correlation coefficients (ICCs) and the Bland-Altman method. RESULTS: The
      repeatability of Scheimpflug photography and scanning-slit corneal topography was
      high (ICC, 0.70 to 0.99). Scheimpflug photography outperformed scanning-slit
      corneal topography for anterior power, posterior power, and total corneal power.
      The reproducibility results were similar, with limits of agreement (LoA)
      consistently narrower for Scheimpflug photography. The between-instrument
      agreement was moderate, with LoA around the mean value of total corneal power of
      0.46 diopter ranging from 0.032 to 0.889. CONCLUSIONS: The results suggest that
      repeatability and reproducibility are higher in Scheimpflug photography than in
      scanning-slit topography. The agreement between rotating Scheimpflug photography
      and scanning-slit topography for total corneal power was moderate.

PMID- 19101436
TI  - Pupil sizes in different Japanese age groups and the implications for intraocular
      lens choice.
AB  - PURPOSE: To observe pupil sizes with near and distance vision under different
      lighting conditions in different Japanese age groups. SETTING: Department of
      Ophthalmology, Tokyo Dental College Suidobashi Hospital, Tokyo, Japan. METHODS:
      Using an open view-type infrared video pupillometer, the horizontal and vertical
      pupil sizes were measured prospectively with subjects gazing at 30 cm or 3 m
      targets under photopic (illumination 500 lux) and mesopic (illumination 5 lux)
      conditions. The results were analyzed by age, and the benefits with various
      multifocal IOLs were evaluated. RESULTS: The study comprised 140 eyes (70
      subjects; 14 to 94 years). The mean +/- standard deviations of photopic vertical
      pupil sizes when gazing far/near decreased from 3.77 +/- 0.23/3.50 +/- 0.33 mm
      (<20 years) to 2.20 +/- 0.30/1.95 +/- 0.20 mm (over 80 years), with pupil sizes
      stabilizing after 60 years. The mesopic vertical pupil sizes when gazing far/near
      decreased from 6.35 +/- 0.11/6.27 +/- 0.14 mm (<20 years) to 3.42 +/- 0.30/3.21
      +/- 0.28 mm (over 80 years). The pupil sizes decreased with age until 60 years
      and stabilized (1-way analysis of variance, P<.05). Fewer than 50% of subjects
      over 60 years of age had pupil sizes conducive to the near zone of refractive
      multifocal intraocular lenses. CONCLUSION: Photopic and scotopic pupil sizes
      decreased with age up to 60 years. The pupil was smaller when gazing at a near
      target than previously reported.

PMID- 19101438
TI  - Second femtosecond laser pass for incomplete laser in situ keratomileusis flaps
      caused by suction loss.
AB  - PURPOSE: To examine the technique of second-pass femtosecond laser to correct an
      incomplete flap during laser in situ keratomileusis. SETTING: Department of
      Ophthalmology, Bascom Palmer Eye Institute, Miami, Florida, USA. METHODS: Twenty
      porcine eyes were assigned to 1 of 4 groups. In the first 2 groups, a flap was
      created with a femtosecond laser with a centrally black-painted applanator at a
      200 microm depth; a second flap was created at a 400 microm depth with the normal
      applanator. These groups differed by waiting or not waiting for the opaque bubble
      layer (OBL) to clear. In the third and fourth groups, the eyes were separated
      into those with and without OBL; however, the same depth was used for the second
      pass, which was performed after intentional suction loss. After these treatments,
      the corneas were examined using anterior segment optical coherence tomography (AS
      OCT) and the surgical microscope. RESULTS: In the first group (did not wait for
      OBL to clear), the peripheral shallow cut and the central deep line were observed
      in the AS-OCT images, with corresponding findings under the surgical microscope.
      In the second group (waited for OBL to disappear), there were 2 parallel lines on
      the AS-OCT images; the lines corresponded to dual flaps. In the third and fourth
      same-depth-cut tests, lines and irregularities were seen on the bed and the back
      of the flap. CONCLUSION: A second femtosecond laser pass for incomplete flaps,
      especially when the OBL has cleared, may result in an uneven lamellar cut.

PMID- 19101437
TI  - Importance of fixation, pupil center, and reference axis in ocular wavefront
      sensing, videokeratography, and retinal image quality.
AB  - PURPOSE: To examine the impact of the location of the fixation target, pupil
      center, and reference axis of ophthalmic aberrometers and videokeratographers on
      the measurement of corneal aberrations relevant to vision. SETTING: Clinical
      Research, Visual Optics Institute, College of Optometry, University of Houston,
      Houston, Texas, USA. METHODS: The design features of a generic aberrometer and
      videokeratographer and their interaction with the eye were examined. The results
      provided a theoretical framework for experimental assessment of pupil translation
      errors on corneal aberrations relevant to vision and their correction in 129
      eyes. RESULTS: Two key principles emerged. First, the aberrometer's measurement
      axis must coincide with the eye's line-of-sight (LoS). Second, the
      videokeratographer's measurement axis (the vertex normal) must be parallel with
      the eye's LoS. When these principles are satisfied, the eye will be in the same
      state of angular rotation and direct comparison of measurements is justified,
      provided any translation of the pupil from the vertex normal is taken into
      account. The error incurred by ignoring pupil displacement in videokeratography
      varies between eyes and depends on the type of aberration and amount of
      displacement, with the largest residual correction root-mean-square wavefront
      error being 1.26 mum over a 6.0 mm pupil, which markedly decreases retinal image
      quality. CONCLUSION: Translation of the pupil center with respect to the vertex
      normal in videokeratography should not be ignored in the calculation of the
      corneal first-surface, internal aberrations of the eye relevant to vision, or the
      design of refractive corrections based on videokeratography.

PMID- 19101439
TI  - Lower- and higher-order aberrations predicted by an optomechanical model of
      arcuate keratotomy for astigmatism.
AB  - PURPOSE: To develop a realistic model of the optomechanical behavior of the
      cornea after curved relaxing incisions to simulate the induced astigmatic change
      and predict the optical aberrations produced by the incisions. SETTING: ICMA
      Consejo Superior de Investigaciones Cientificas and Universidad de Zaragoza,
      Zaragoza, Spain. METHODS: A 3-dimensional finite element model of the anterior
      hemisphere of the ocular surface was used. The corneal tissue was modeled as a
      quasi-incompressible, anisotropic hyperelastic constitutive behavior strongly
      dependent on the physiological collagen fibril distribution. Similar behaviors
      were assigned to the limbus and sclera. With this model, some corneal incisions
      were computer simulated after the Lindstrom nomogram. The resulting geometry of
      the biomechanical simulation was analyzed in the optical zone, and finite ray
      tracing was performed to compute refractive power and higher-order aberrations
      (HOAs). RESULTS: The finite-element simulation provided new geometry of the
      corneal surfaces, from which elevation topographies were obtained. The surgically
      induced astigmatism (SIA) of the simulated incisions according to the Lindstrom
      nomogram was computed by finite ray tracing. However, paraxial computations would
      yield slightly different results (undercorrection of astigmatism). In addition,
      arcuate incisions would induce significant amounts of HOAs. CONCLUSIONS: Finite
      element models, together with finite ray-tracing computations, yielded realistic
      simulations of the biomechanical and optical changes induced by relaxing
      incisions. The model reproduced the SIA indicated by the Lindstrom nomogram for
      the simulated incisions and predicted a significant increase in optical
      aberrations induced by arcuate keratotomy.

PMID- 19101440
TI  - Performance of presbyopia-correcting intraocular lenses in distance optical bench
      tests.
AB  - PURPOSE: To compare the optical performance of 6 presbyopia-correcting
      intraocular lenses (IOLs) of different designs (accommodating or multifocal and
      aspheric or spheric). SETTING: Alcon Laboratories, Inc., Fort Worth, Texas, USA.
      METHODS: The optical performance of 6 IOLs were compared using modulation
      transfer function (MTF) and the United States Air Force 1951 Resolution Target
      (AFT) testing. The IOLs included 3 spheric designs (Crystalens AT-50SE, AcrySof
      ReSTOR SA60D3, and ReZoom NXG1) and 3 aspheric designs (AcrySof ReSTOR SN6AD3,
      Acri.Lisa 366D, and Tecnis ZM900). Tests were performed with a modified
      International Organization for Standardization (ISO) model eye with a 5.0 mm
      aperture at the distance focus. RESULTS: The ReSTOR aspheric IOL had the highest
      MTF values at all spatial frequencies, and the ReZoom IOL had the lowest MTF
      values at most spatial frequencies. The ReSTOR aspheric IOL produced the image
      with the highest resolution on the AFT test; the Tecnis and the ReZoom IOLs
      produced the images with the poorest resolution. The Acri.Lisa multifocal IOL was
      second to the ReSTOR aspheric IOL on the MTF test and had high resolution on the
      AFT test. The accommodating Crystalens performed poorly on the MTF test but had
      the second highest resolution on the AFT test. CONCLUSIONS: The AcrySof ReSTOR
      SN6AD3 aspheric IOL showed superior optical properties, demonstrated in MTF and
      AFT optical bench testing, among 6 presbyopia-correcting IOLs including the
      monofocal accommodating Crystalens. The Acri.Lisa IOL also performed well. The
      ReZoom IOL demonstrated the poorest overall optical quality.

PMID- 19101441
TI  - Analysis of the possible benefits of aspheric intraocular lenses: review of the
      literature.
AB  - We reviewed recently published studies that analyzed the visual and optical
      quality in eyes with different spherical and aspheric intraocular lenses (IOLs).
      Recent studies focused on visual quality metrics, such as visual acuity and
      contrast sensitivity, under photopic and mesopic lighting conditions and optical
      metrics, such as wavefront aberrations, especially spherical aberration. The
      results in this review were used in an attempt to understand whether there is a
      visual and/or optical benefit of implanting aspheric IOLs over implanting
      spherical IOLs.

PMID- 19101442
TI  - Limbal relaxing incisions and Graves ophthalmopathy with lower eyelid retraction.
AB  - Limbal relaxing incisions (LRI) were performed in a 35-year-old man with Graves
      ophthalmopathy and lower eyelid retraction. He underwent intraocular lens
      exchange in 1 eye and cataract surgery in the other. Despite the return of normal
      thyroid function, aggressive lubrication, and antiinflammatory medication, the
      LRIs failed to heal, leaving gaps in the limbal cornea. Limbal relaxing incisions
      should be avoided in Graves ophthalmopathy with lower eyelid retraction and/or
      exposure keratopathy.

PMID- 19101443
TI  - Corneal melt in lattice corneal dystrophy type II after cataract surgery.
AB  - We report a patient with lattice corneal dystrophy type II, also known as
      Meretoja syndrome or familial amyloidosis Finnish type, who developed a corneal
      melt 15 days after uneventful phacoemulsification. Despite conservative
      treatment, the corneal melt resulted in perforation. Uneventful penetrating
      keratoplasty was performed, but delayed graft epithelial healing was noticed
      postoperatively. Corneal button histopathological evaluation confirmed the
      initial clinical diagnosis. To our knowledge, this is the first reported case of
      corneal melt and perforation in a patient with lattice corneal dystrophy type II.

PMID- 19101444
TI  - Argon laser iridotomy as a possible cause of anterior dislocation of a
      crystalline lens.
AB  - We report a case of spontaneous dislocation of the crystalline lens into the
      anterior chamber in a patient with no history of trauma or any systemic disease
      associated with zonular dialysis. Anterior lens dislocation developed 10 months
      after argon laser iridotomy had been performed for angle-closure glaucoma. We
      suspect the argon laser iridotomy might have induced localized zonular dialysis
      that resulted in progressive zonular weakness and, finally, lens dislocation into
      the anterior chamber.

PMID- 19101445
TI  - Epithelial downgrowth after Descemet-stripping automated endothelial
      keratoplasty.
AB  - A 66-year-old man presented with decreased vision and corneal edema after 2
      failed Descemet-stripping automated endothelial keratoplasty (DSAEK) graft
      procedures in the left eye. An uneventful third DSAEK procedure combined with
      anterior vitrectomy through the previous limbal wound was performed.
      Postoperative recovery was uneventful. Histopathology of the excised failed graft
      revealed conjunctival epithelium on the posterior surface of the tissue. At 1
      year, the endothelial cell count was 1997 cells/mm(2) and the uncorrected visual
      acuity was 20/20(-2). At 18 months, the graft remained clear with no signs of
      epithelial downgrowth. Clinicians should be aware that epithelial downgrowth can
      occur following DSAEK surgery. Fortunately, excision of the prior DSAEK graft
      with removal of the active epithelial membrane appears to have been a successful
      treatment in this patient.

PMID- 19101446
TI  - Single intrastromal corneal ring segment implantation using the femtosecond laser
      after radial keratotomy in a keratoconic patient.
AB  - A 33-year-old woman with irregular astigmatism 6 years after radial keratotomy
      (RK) for keratoconus was treated with implantation of a single intrastromal
      corneal ring segment (Keraring) using the femtosecond laser. The segment (0.150
      mm thick with a 160-degree arc) was inserted in the steepest area (inferior) with
      no intraoperative or postoperative complications. Six months postoperatively, the
      uncorrected visual acuity had improved from 20/40 to 20/25 and the best spectacle
      corrected visual acuity, from 20/32 to 20/20. The mean manifest astigmatic
      correction decreased from -2.50 diopters (D) to -0.75 D, and corneal topography
      showed improved inferior steepening and less irregular astigmatism. Although the
      results are encouraging, the long-term effect of this approach in post-RK
      patients is not known.

PMID- 19101447
TI  - Medical management of acutely recurring pterygium with topical mitomycin-C.

PMID- 19101448
TI  - Ophthalmology carbon footprint: something to be considered?

PMID- 19101449
TI  - Range of drugs associated with IFIS.

PMID- 19101450
TI  - Addressing the mental health service needs of foster youth during the transition
      to adulthood: how big is the problem and what can states do?

PMID- 19101451
TI  - Migration, acculturation, and sexual and reproductive health of Latino
      adolescents.

PMID- 19101452
TI  - Confronting the intendedness of adolescent rapid repeat pregnancy.

PMID- 19101453
TI  - Pediatric to adult mental health service use of young people leaving the foster
      care system.
AB  - PURPOSE: To assess and predict changes in mental health service use as older
      youth leave the foster care system. METHODS: Participants were 325 19-year-olds
      participating in a longitudinal study of older youth leaving the foster care
      system in Missouri. All were in the foster care system at age 17. Participants
      were interviewed nine times between their 17th and 19th birthdays using the
      Service Assessment for Children and Adolescents and a history calendar to improve
      recall of service history. Analyses included Cox proportional hazards regression
      to predict time to service stoppage and McNemar's test to assess difference in
      rates of service use between age 17 and 19. RESULTS: Mental health service use
      dropped dramatically across the study period for all services. Service rates
      dropped most steeply for youth who left the foster care system. Service use rates
      declined by roughly 60% from the month prior to leaving the foster care system to
      the month after leaving the system. Most young adults who stopped pharmacotherapy
      following discharge from foster care reported they did so of their own volition.
      CONCLUSIONS: Practitioners should be aware of the possibility of patient
      initiated mental health service discontinuation following exit from the foster
      care system and plan accordingly.

PMID- 19101454
TI  - Immigration measures and reproductive health among Hispanic youth: findings from
      the national longitudinal survey of youth, 1997-2003.
AB  - PURPOSE: To explore relationships between immigration measures and risk of
      reproductive and sexual events among U.S. Hispanic adolescents. METHODS: We
      examined generation status, language in the home and country of origin in
      relation to sexual activity, contraception, and childbearing among 1614 Hispanic
      adolescents, using nationally representative 1997-2003 longitudinal data.
      Multivariable analyses controlled for potentially confounding variables. Tests
      for effect modification by gender and Mexican origin were conducted. RESULTS:
      Fewer first generation adolescents transitioned to sexual intercourse before age
      18 (odds ratio [OR]=.80, 95% confidence interval [CI]=.66-.98) and fewer first
      and second generation sexually active teens used contraceptives consistently at
      age 17 (OR=.32, 95% CI=.17-.60 and OR=.50, 95% CI=.31-.80, respectively) than
      third-generation teens. Language was similarly associated with the transition to
      sexual intercourse and contraceptive practices. Versus teens of Mexican origin,
      teens of Puerto Rican origin and origins other than Cuba and Central/South
      America had greater odds of becoming sexually active; youth of all origins except
      Central/South America had fewer multiple live births (OR=.14-.31). Gender
      modified the effects of generation on consistent use of contraceptives and
      condoms at age 17. Gender also modified the effect of country of origin on
      transitioning to sexual intercourse before age 18 years. CONCLUSIONS: Results
      expand on previous observations that generation, language, and country of origin
      are predictors of reproductive and sexual risks for Hispanic adolescents. These
      immigration measures may therefore be useful in targeting community and clinical
      preventive services.

PMID- 19101456
TI  - Immunogenicity and safety of human papillomavirus (HPV)-16/18 AS04-adjuvanted
      vaccine in healthy boys aged 10-18 years.
AB  - PURPOSE: The human papillomavirus (HPV)-16/18 AS04-adjuvanted vaccine (Cervarix)
      has been shown to be well-tolerated and immunogenic in females aged 10 to 55
      years, and up to 100% effective for the prevention of HPV-16/18 infection and
      associated precancerous cervical lesions in females aged 15 to 25 years. This
      study is the first to evaluate the immunogenicity and safety of the vaccine in
      males. METHODS: Healthy males aged 10 to 18 years were randomized (2:1 ratio) to
      receive HPV-16/18 AS04-adjuvanted vaccine (n = 181) or hepatitis B virus (HBV)
      control vaccine (n = 89) at 0, 1, and 6 months, and were followed for 7 months.
      RESULTS: All initially seronegative subjects in the HPV-16/18 group seroconverted
      for HPV-16 and 18 (ELISA) at month 2. At month 7, all subjects were seropositive,
      and the HPV-16 and -18 antibody levels were, respectively, four- and twofold
      higher than at month 2. The anti-HPV-16 and -18 antibody responses for males aged
      10 to 18 years and 10 to 14 years, respectively, were higher than those reported
      for females aged 15 to 25 years and 10 to 14 years, respectively, in a previous
      study. The reactogenicity profiles of the HPV-16/18 AS04 and HBV vaccines were
      similar, except that pain and swelling at the injection site were more common in
      the HPV-16/18 group. However, vaccine-related symptoms did not affect compliance
      with the three-dose course, which was equally high (97%) in both groups.
      CONCLUSIONS: The HPV-16/18 AS04-adjuvanted vaccine is immunogenic and well
      tolerated in boys aged 10 to 18 years. However, further data on the potential
      public health benefits of vaccination of boys are required before any
      recommendations can be made.

PMID- 19101455
TI  - The role of mental health factors, behavioral factors, and past experiences in
      the prediction of rapid repeat pregnancy in adolescence.
AB  - PURPOSE: This study investigates the predictors of rapid repeat pregnancy
      (subsequent pregnancy within 24 months of previous pregnancy outcome) in a sample
      of urban adolescents. METHODS: Adolescents aged 12-19 years (N = 354) who were
      predominantly African-American (94.1%) completed individual interviews during
      pregnancy and at 24 months postpartum. Logistic regression was used to determine
      the relationship among mental health factors, behavioral factors, and negative
      life experiences in the prediction of rapid repeat pregnancy. RESULTS: Of the
      adolescents, 42% (n = 147) of adolescents reported a rapid repeat pregnancy.
      Baseline reports of later age at menarche (12.43 vs. 11.91; p = .003) and a
      greater likelihood of aggression were significantly associated with having a
      rapid repeat pregnancy within 24 months. Age at menarche and self-reported
      aggression contributed independently to the prediction of a closely spaced second
      pregnancy (p < .05). CONCLUSIONS: It is suggested that pubertal onset and
      individual mental health as it relates to measures of aggression should be
      considered when developing programs targeting adolescents at highest risk for
      rapid repeat pregnancy.

PMID- 19101457
TI  - Health insurance discontinuities among adolescents leaving foster care.
AB  - PURPOSE: To determine whether adolescents who lose Medicaid entitlements when
      they leave foster care are subsequently able to secure employer-sponsored or
      student health insurance coverage. METHODS: This was a 2-year follow-up study of
      a cohort of 404 adolescents leaving foster care in eight counties in a midwestern
      state. We conducted survival analysis to study predictors of time to first
      insurance loss, and logistic regression analysis to determine factors associated
      with insurance reacquisition, among these youth. RESULTS: A total of 206
      adolescents (51%) left foster care during follow up, of whom 138 (67%) lost
      health insurance coverage within a mean of 3 months of leaving foster care. Those
      who regained coverage (34; 17% of those leaving foster care) did so after a mean
      period of 8 months spent without insurance. Hazard of insurance loss was lower
      for employed adolescents (HR=.5; 95% CI=.4-.7; p < .0001), but only half of all
      adolescents leaving foster care reported being able to secure employment. Student
      health insurance did not reduce hazard of insurance loss. Boys had significantly
      lower odds of regaining insurance compared with girls (OR=.2, SE=.5, p=.003).
      CONCLUSIONS: Most youth leaving the child welfare system seem unable to
      transition to other forms of health insurance coverage. Even those that do
      acquire coverage, do so after an inordinate period of time. Enacting existing
      extensions of Medicaid coverage until age 21 for foster care youth is necessary
      to provide the resources to address the considerable health and mental health
      needs among these youth.

PMID- 19101458
TI  - Discussion of sensitive health topics with youth during primary care visits:
      relationship to youth perceptions of care.
AB  - PURPOSE: Youth have concerns about sensitive health topics, such as drugs, sex,
      and mental health, and many wish to discuss those concerns with a primary care
      provider. Research has not determined whether the discussion of sensitive health
      topics during primary care visits is independently associated with youth
      perceptions of care. This study examined whether the discussion of sensitive
      health topics during primary care visits was associated with youth's perceptions
      of the provider and of participation in treatment. METHODS: Directly after visits
      to 54 primary care providers in 13 geographically diverse offices and clinics,
      youth age 11-16 years old (N = 358) reported whether the visit included the
      discussion of mood, behavior, getting along with others, drugs, tobacco, alcohol,
      sexuality, birth control, parent mood, or family problems. Youth also reported
      whether the provider understood their problems, eased their worries, allowed them
      to make decisions about treatment, gave them some control over treatment, and
      asked them to take some responsibility for treatment. Providers reported
      confidence in their ability to offer counseling for nonmedical concerns and their
      beliefs and attitudes toward treating nonmedical concerns. RESULTS: Youth had
      more positive perceptions of the provider and were more likely to report taking
      an active role in treatment when the visit included the discussion of a sensitive
      health topic. Results from multivariate random effects logistic regression
      suggested that youth were more likely to report that the provider understood
      their problems (OR = 3.62, CI = 1.57-8.31), eased their worries (OR = 2.13, CI =
      1.06-3.92), allowed them to make decisions about treatment (OR = 2.71, CI = 1.44
      5.10), gave them some control over treatment (OR = 2.51, CI = 1.32-4.71), and
      asked them to take some responsibility for treatment (OR = 2.00, CI = 1.04-3.86)
      when the visit included the discussion of one or more sensitive health topics.
      The odds of each of these outcomes were also higher when the visit included the
      discussion of a greater number of sensitive topics. Youth also had more positive
      perceptions of female providers. Youth demographics, mental health status, and
      other provider characteristics were unrelated to youth perceptions of care.
      CONCLUSIONS: The discussion of sensitive health topics during primary care visits
      may have a positive impact on youth perceptions of care. Future research is
      needed to understand the relationship between the discussion of sensitive health
      topics and health outcomes among youth.

PMID- 19101460
TI  - How do school-day activity patterns differ with age and gender across
      adolescence?
AB  - PURPOSE: A knowledge of how young people use their time could be instrumental in
      informing health interventions, modeling consumer behaviors, and planning service
      delivery. The aim of the present study was to describe age- and gender-related
      patterns in the self-reported use of time on school days in a large sample of
      Australian children and adolescents aged between 10 and 18 years. METHODS: A
      single, detailed use-of-time diary for a school day was collected from 6024
      Australians aged 10-18 from several state and regional surveys conducted in the
      states of South Australia (SA) and Victoria between 2001 and 2006. Time-use
      profiles were analyzed for a range of active and sedentary state behaviors.
      RESULTS: Boys reported higher physical activity levels (PALs), moderate-to
      vigorous physical activity (MVPA), and sports than girls. There were no
      differences in free play, and girls used more active transport. All activity
      related variables decreased with age, except active transport, which peaked at 14
      15 years. Boys exhibited higher levels of screen time, whereas girls had higher
      levels of passive transport. Screen time and its components (television,
      videogames, and computer use) peaked in the peripubertal years. CONCLUSION: Age-
      and gender-related patterns of time use vary greatly within adolescence. This may
      reflect a mix of biological and social factors.

PMID- 19101461
TI  - Alcohol, helping young adults to have unprotected sex with casual partners:
      findings from a daily diary study of alcohol use and sexual behavior.
AB  - PURPOSE: To examine the event-level association between alcohol consumption and
      the likelihood of unprotected sex among college-age young adults considering
      contextual factors of partner type and amount of alcohol consumed. METHODS: A 30
      day, Web-based, structured daily diary was used to collect daily reports of
      sexual behaviors and alcohol use from 116 sexually active young adults, yielding
      2,764 diary records. Each day we assessed the prior evening's behavior regarding
      alcohol consumption, opportunities for sex, sexual intercourse, condom use, and
      contextual factors including type of sexual partner. RESULTS: Based on multilevel
      models, drinking proximal to events of sexual intercourse increased the
      likelihood of unprotected sex with casual but not steady partners. For women
      there was a positive association between number of drinks and a greater
      likelihood of unprotected sex with casual partners but a negative association
      with steady partners. Drinking during situations involving opportunities for sex
      with casual partners increased the likelihood of sex. For women especially,
      drinking more increased the likelihood of sex occurring regardless of partner
      type. CONCLUSIONS: Failure to assess the contextual determinants of the alcohol
      unprotected sex association may result in underestimates of the magnitude of this
      association. These data highlight an important area for intervention with young
      adults: reducing alcohol-involved sexual risk behavior with casual partners,
      especially among women.

PMID- 19101459
TI  - Contraceptive method at first sexual intercourse and subsequent pregnancy risk:
      findings from a secondary analysis of 16-year-old girls from the RIPPLE and SHARE
      studies.
AB  - PURPOSE: Existing failure rate studies indicate that typical use of oral
      contraception (OC) results in fewer unplanned pregnancies than condom use, even
      among teenagers. However, comparative data on pregnancy risk associated with
      different contraceptive methods are lacking for younger teenagers starting their
      first sexual relationship. This study examined associations between contraceptive
      method at first intercourse and subsequent pregnancy in 16-year-old girls.
      METHODS: Six thousand three hundred forty-eight female pupils from 51 secondary
      schools completed a questionnaire at mean age 16 years; 2,501 girls reported
      sexual intercourse. Logistic regression (N = 1952) was used to model the
      association of contraceptive method at first intercourse with pregnancy. RESULTS:
      At first intercourse (median age 15 years) 54% reported using condoms only, 11%
      dual OC and condoms, 4% OC only, 4% emergency contraception, and 21% no effective
      method. Method used was associated with a similar method at a most recent
      intercourse. One in 10 girls reported a pregnancy. When compared to use of
      condoms only, greater pregnancy risk was found with no effective method (odds
      ratio [OR] 2.97, 95% confidence interval [CI] 2.12-4.15) or OC only (OR 2.44, 95%
      CI 1.29-4.60). Pregnancy risk for dual use and emergency contraception did not
      differ from that for condoms only. Both significant effects were partially
      attenuated by adjusting for user characteristics and sexual activity.
      CONCLUSIONS: Young teenagers may use OC less efficiently than condoms for
      pregnancy prevention. The characteristics of those using OC-only confirm
      vulnerability to unintended pregnancy, and suggest that alternative contraceptive
      strategies should be considered for these young women.

PMID- 19101462
TI  - Emergency department management of adolescents with urinary complaints: missed
      opportunities.
AB  - Practice recommendations for the evaluation of adolescents with urinary
      complaints advise taking a sexual history and testing for sexually transmitted
      infections (STIs). In this emergency department chart review, 30% lacked a
      documented sexual history and 49% of sexually active patients were not STI
      tested, representing missed opportunities for diagnosis of STIs.

PMID- 19101463
TI  - Does calorie information promote lower calorie fast food choices among college
      students?
AB  - This experiment evaluated effects of calorie information on college students'
      fast food choices. Women chose lower calorie meals, lower calorie items, and
      lower priced meals when calorie information was provided than when it was not.
      Men's selections were unaffected. Providing calorie information at point of
      purchase could have positive implications for public health.

PMID- 19101464
TI  - Alcohol-related risk behaviors and sports participation among adolescents: an
      analysis of 2005 Youth Risk Behavior Survey data.
AB  - Using 2005 Youth Risk Behavior Survey data, we examined alcohol-related behaviors
      among adolescent sports participants. Male sports participants were more likely
      to report heavy drinking and driving after drinking in the past month. Females
      were less likely to report ever drinking, early drinking, and drinking in the
      past month.

PMID- 19101465
TI  - Can media effects counteract legislation reforms? The case of adolescent firearm
      suicides in the wake of the Austrian firearm legislation.
AB  - To assess the impact of the Austrian firearm legislation (1997) on adolescent
      suicides, we investigated time trends in youth suicide prevalence (1986-2006)
      with Poisson regression. A temporary increase in firearm suicides after the
      reform was observed, followed by a continuous decrease. The hypothesis that media
      reporting triggered the short-term backlash effect is discussed.

PMID- 19101466
TI  - Lipoatrophic diabetes: a case report with a brief review of the literature.
AB  - Lipoatrophy syndromes are characterized by an absence of adipose tissue and low
      leptin levels. Metabolic derangements associated with these syndromes can include
      diabetes mellitus, insulin resistance, and hyperlipidemia.

PMID- 19101467
TI  - Finger pointing: engineered zinc-finger proteins allow precise modification and
      regulation of genes.

PMID- 19101468
TI  - Tracing the silhouette of individual cells in S/G2/M phases with fluorescence.
AB  - The APC(Cdh1) E3 ligase is active in the late M and G(1) phases. Geminin is a
      direct substrate of the APC(Cdh1) complex, and accumulates during the S, G(2),
      and M phases. By fusing the amino-terminal region of Geminin to fluorescent
      proteins, we have developed cell cycle markers that accumulate in the S/G(2)/M
      phases in both the nucleus and the cytoplasm. These markers reveal the morphology
      of individual cells that have undergone DNA replication, allowing us to monitor
      cell growth relative to differentiation of various cell types. After
      electroporating the developing mouse embryos, we highlighted neuroepithelial
      progenitors in the S/G(2)/M phases, which possessed an elongated morphology with
      an apical and/or a basal attachment. We also show that nuclear localization of
      the ubiquitin ligase for Geminin is essential for full performance of the
      markers.

PMID- 19101469
TI  - Inhibition and dispersion of Pseudomonas aeruginosa biofilms by glycopeptide
      dendrimers targeting the fucose-specific lectin LecB.
AB  - The human pathogenic bacterium Pseudomonas aeruginosa produces a fucose-specific
      lectin, LecB, implicated in tissue attachment and the formation of biofilms. To
      investigate if LecB inhibition disrupts these processes, high-affinity ligands
      were obtained by screening two 15,536-member combinatorial libraries of
      multivalent fucosyl-peptide dendrimers. The most potent LecB-ligands identified
      were dendrimers FD2 (C-Fuc-LysProLeu)(4)(LysPheLysIle)(2)LysHisIleNH(2) (IC(50) =
      0.14 microM by ELLA) and PA8 (OFuc-LysAlaAsp)(4)(LysSerGlyAla)(2)LysHisIleNH(2)
      (IC(50) = 0.11 microM by ELLA). Dendrimer FD2 led to complete inhibition of P.
      aeruginosa biofilm formation (IC(50) approximately 10 microM) and induced
      complete dispersion of established biofilms in the wild-type strain and in
      several clinical P. aeruginosa isolates. These experiments suggest that LecB
      inhibition by high-affinity multivalent ligands could represent a therapeutic
      approach against P. aeruginosa infections by inhibition of biofilm formation and
      dispersion of established biofilms.

PMID- 19101470
TI  - Supramolecular iron cylinder with unprecedented DNA binding is a potent
      cytostatic and apoptotic agent without exhibiting genotoxicity.
AB  - The supramolecular iron cylinder, [Fe(2)L(3)]Cl(4) (L = C(25)H(20)N(4)), shows
      unprecedented DNA binding in vitro, inducing intramolecular DNA coiling and also
      targeting Y-shaped DNA junctions. We investigated its effects on proliferation
      and survival in both tumor and normal cell lines. Iron cylinder reduced
      mitochondrial activity of cultures with potency similar to cisplatin, inhibited
      the cell cycle, and increased cell death by apoptosis. Associated with this, we
      observed a lowering of the association of propidium iodide with cellular DNA
      consistent with an observed competitive displacement of PI from naked DNA by
      cylinders. Importantly, and in contrast to existing anticancer drugs such as
      cisplatin, the iron cylinder [Fe(2)L(3)](4+) was not genotoxic. In summary, the
      design of metal complexes such as [Fe(2)L(3)](4+) with potential anticancer
      properties in the absence of genotoxicity may represent a significant step toward
      therapeutic advancement.

PMID- 19101471
TI  - In vitro reconstituted biotransformation of 4-fluorothreonine from fluoride ion:
      application of the fluorinase.
AB  - In this paper, we report that fluoride ion is converted to the amino
      acid/antibiotic 4-fluorothreonine 2 in a biotransformation involving five (steps
      a-e) overexpressed enzymes. The biotransformation validates the biosynthetic
      pathway to 4-fluorothreonine in the bacterium Streptomyces cattleya (Schaffrath
      et al., 2002). To achieve an in vitro biotransformation, the fluorinase and the
      purine nucleoside phosphorylase (PNP) enzymes (steps a and b), which are coded
      for by the flA and flB genes of the fluorometabolite gene cluster in S. cattleya,
      were overexpressed. Also, an isomerase gene product that can convert 5-FDRP 6 to
      5-FDRibulP 7 (step c) was identified in S. cattleya, and the enzyme was
      overexpressed for the biotransformation. A fuculose aldolase gene from S.
      coelicolor was overexpressed in E. coli and was used as a surrogate aldolase
      (step d) in these experiments. To complete the complement of enzymes, an ORF
      coding the PLP-dependent transaldolase, the final enzyme of the fluorometabolite
      pathway, was identified in genomic DNA by a reverse genetics approach, and the S.
      cattleya gene/enzyme was then overexpressed in S. lividans. This latter enzyme is
      an unusual PLP-dependent catalyst with some homology to both bacterial serine
      hydroxymethyl transferases (SHMT) and C5 sugar isomerases/epimerases. The
      biotransformation demonstrates the power of the fluorinase to initiate C-F bond
      formation for organo-fluorine synthesis.

PMID- 19101472
TI  - Directed evolution of a lysosomal enzyme with enhanced activity at neutral pH by
      mammalian cell-surface display.
AB  - Human beta-glucuronidase, due to low intrinsic immunogenicity in humans, is an
      attractive enzyme for tumor-specific prodrug activation, but its utility is
      hindered by low activity at physiological pH. Here we describe the development of
      a high-throughput screening procedure for enzymatic activity based on the stable
      retention of fluorescent reaction product in mammalian cells expressing properly
      folded glycoproteins on their surface. We utilized this procedure on error-prone
      PCR and saturation mutagenesis libraries to isolate beta-glucuronidase tetramers
      that were up to 60-fold more active (k(cat)/K(m)) at pH 7.0 and were up to an
      order of magnitude more effective at catalyzing the conversion of two
      structurally disparate glucuronide prodrugs to anticancer agents. The screening
      procedure described here can facilitate investigation of eukaryotic enzymes
      requiring posttranslational modifications for biological activity.

PMID- 19101473
TI  - Known bioactive small molecules probe the function of a widely conserved but
      enigmatic bacterial ATPase, YjeE.
AB  - Escherichia coli YjeE is a broadly conserved bacterial ATPase of unknown function
      that has been widely characterized as essential. Here, the transcriptional
      regulation of the promoter of yjeE (P(yjeE)) was probed using a luciferase
      reporter and 172 antibiotics of diverse mechanisms. Norfloxacin and other
      fluorquinolones were found to be the most potent activator of P(yjeE) through
      binding to DNA gyrase. The stimulation of P(yjeE) by norfloxacin was most
      impacted by lesions in two-component signal transduction systems with roles in
      respiration, central metabolism, and oxidative stress responses. This suggested
      that YjeE may have a critical role in aerobic metabolism. Remarkably, YjeE was
      found to be dispensable when cells were grown in the absence of oxygen. To the
      best of our knowledge, these findings represent the first definitive phenotypes
      for this enigmatic protein.

PMID- 19101474
TI  - Targeting a uniquely nonspecific prenyl synthase with bisphosphonates to combat
      cryptosporidiosis.
AB  - Cryptosporidiosis is a neglected disease without a wholly effective drug. We
      present a study demonstrating nitrogen-containing bisphosphonates (N-BPs) to be
      capable of inhibiting Cryptosporidium parvum at low micromolar concentrations in
      infected MDCK cells. Predictably, the mechanism of action is based on inhibition
      of biosynthesis of isoprenoids but the target enzyme is unexpectedly a
      distinctive C. parvum enzyme dubbed nonspecific polyprenyl pyrophosphate synthase
      (CpNPPPS). This enzyme produces various isoprenoid products larger than FPP and
      is inhibited by N-BPs at subnanomolar concentrations. It is part of an isoprenoid
      pathway in Cryptosporidium distinctly different from other organisms. The
      proposed mechanism of action is corroborated by crystal structures of the enzyme
      with risedronate and zoledronate bound showing how this enzyme's unique chain
      length determinant region enables it to accommodate larger substrates and
      products. These results, combined with existing data on their clinical use,
      demonstrate that N-BPs are very promising anticryptosporidial drug candidates.

PMID- 19101475
TI  - Nitrosothiol reactivity profiling identifies S-nitrosylated proteins with
      unexpected stability.
AB  - Nitric oxide (NO) regulates protein function by S-nitrosylation of cysteine to
      form nitrosothiols. Nitrosothiols are highly susceptible to nonenzymatic
      degradation by cytosolic reducing agents. Here we show that although most protein
      nitrosothiols are rapidly degraded by cytosolic reductants, a small subset form
      unusually stable S-nitrosylated proteins. Our findings suggest that stable S
      nitrosylation reflects a protein conformation change that shields the
      nitrosothiol. To identify stable protein nitrosothiols, we developed a proteomic
      method for profiling S-nitrosylation. We examined the stability of over 100 S
      nitrosylated proteins, and identified 10 stable nitrosothiols. These proteins
      remained S-nitrosylated in cells after NO synthesis was inhibited, unlike most S
      nitrosylated proteins. Taken together, our data identify a class of NO targets
      that form stable nitrosothiols in the cell and are likely to mediate the
      persistent cellular effects of NO.

PMID- 19101476
TI  - The importance of odorant conformation to the binding and activation of a
      representative olfactory receptor.
AB  - Olfactory receptors (ORs) form a large family of G protein-coupled receptor
      proteins (GPCRs) responsible for sensing the ambient chemical environment. The
      molecular recognition strategies used by ORs to detect and distinguish odorant
      molecules are unclear. Here, we investigated the variable of odorant carbon chain
      conformation for an established odorant-OR pair: n-octanal and rat OR-I7. A
      series of conformationally restricted octanal mimics were tested on live
      olfactory sensory neurons (OSNs). Our results support a model in which
      unactivated OR-I7 binds aliphatic aldehydes indiscriminately, and then applies
      conformational and length filters to distinguish agonists from antagonists.
      Specific conformers are proposed to activate OR-I7 by steric buttressing of an OR
      activation pocket. Probing endogenously expressed rat OSNs with octanal and
      constrained mimics furnished evidence that odorant conformation contributes to an
      odorant's unique olfactory code signature.

PMID- 19101477
TI  - Functional characterization of the biosynthesis of radicicol, an Hsp90 inhibitor
      resorcylic acid lactone from Chaetomium chiversii.
AB  - Fungal polyketides with the resorcylic acid lactone (RAL) scaffold are of
      interest for growth stimulation, the treatment of cancer, and neurodegenerative
      diseases. The RAL radicicol is a nanomolar inhibitor of the chaperone Hsp90,
      whose repression leads to a combinatorial blockade of cancer-causing pathways.
      Clustered genes for radicicol biosynthesis were identified and functionally
      characterized from the endophytic fungus Chaetomium chiversii, and compared to
      recently described RAL biosynthetic gene clusters. Radicicol production is
      abolished upon targeted inactivation of a putative cluster-specific regulator, or
      either of the two polyketide synthases that are predicted to collectively
      synthesize the radicicol polyketide core. Genomic evidence supports the existence
      of flavin-dependent halogenases in fungi: inactivation of such a putative
      halogenase from the C. chiversii radicicol locus yields dechloro-radicicol
      (monocillin I). Inactivation of a cytochrome P450 epoxidase furnishes pochonin D,
      a deepoxy-dihydro radicicol analog.

PMID- 19101479
TI  - Medical management update: Non-Hodgkin lymphoma.
AB  - Lymphoma is a heterogeneous malignancy of the lymphatic system characterized by
      proliferation of lymphoid cells or their precursors. Non-Hodgkin lymphoma (NHL)
      is associated with significant morbidity and is the seventh leading cause of
      death in the United States. Manifestations of NHL as well as complications of the
      disease and its management are frequently encountered in the head and neck region
      and often require specific treatment and modifications in the provision of oral
      health care. The purpose of this article is to review current concepts of the
      pathophysiology, as well as medical and oral health care management of NHL.

PMID- 19101478
TI  - Association between IFN-alpha and primary Sjogren's syndrome.
AB  - OBJECTIVE: To determine the level of IFN-alpha in labial salivary glands, plasma,
      and peripheral blood cells from patients with primary Sjogren's syndrome (pSS).
      METHODS: Labial salivary gland biopsy specimens, plasma, and peripheral blood
      cells from patients with pSS were investigated. The IFN-alpha-positive cells,
      measurable IFN-alpha level, and IFN-alpha gene mRNA level were determined by
      using immunohistochemistry, ELISA, and real-time PCR, respectively. Statistical
      analysis was performed by Student t test or Fisher's exact test. RESULTS: About
      60% of patients (22/37) with pSS had significantly higher scores of IFN-alpha
      positive cells in labial gland biopsy and most IFN-alpha-positive cells were
      localized predominantly in the lymphocytes and ductal epithelial cells. But in 3
      of the control samples (3/24), the IFN-alpha-positive cells existed only in the
      ductal epithelial cells with lower scores. Forty-three percents of the patients
      with pSS were found with detectable IFN-alpha concentration in plasma (> or =
      12.5 pg/mL), and their concentration was higher than that of control group.
      Furthermore, the IFN-alpha mRNA levels in peripheral blood cells were up
      regulated in the patients with pSS. CONCLUSION: No matter in labial salivary
      glands or hematoplasma, or peripheral blood cells, IFN-alpha expression levels
      are up-regulated in patients with primary Sjogren's syndrome.

PMID- 19101480
TI  - Osteonecrosis of the mandibular condyle as a precursor to osteoarthrosis: a case
      report.
AB  - Osteonecrosis of the mandibular condyle is a rare condition characterized by a
      primary subchondral osseous breakdown of the condyle with secondary articular
      surface collapse. Despite these characteristics, it has proved to be difficult to
      diagnose. The present case of osteonecrosis of the mandibular condyle was
      initially diagnosed more than 2 years before. The diagnosis at that time was
      based on physical examination, plain film radiography, cone-beam computerized
      tomography, magnetic resonance imaging, and total body scintigraphy. The disease
      had progressed into severe osteoarthrosis at a 2-year follow-up using cone-beam
      computerized tomography. This report suggests that osteonecrosis may be a
      precursor of osteoarthrosis, and cone-beam computerized tomography may provide a
      sensitive radiographic technique for the diagnosis of osteonecrosis of mandibular
      condyle.

PMID- 19101481
TI  - Orbital complications due to an acute odontogenic focus in a child. A case
      report.
AB  - The full clinical manifestations of complications due to odontogenic foci are
      rarely seen in daily dental practice and can take a clinically foudroyant course
      of development in young people owing to anatomic conditions, as demonstrated in
      this clinical case in a 12-year-old girl. Endodontic treatment of the first right
      upper molar was started owing to increasing toothache and swelling of fossa
      canina and the periorbital region. During the course of treatment, the patient
      exhibited an acute increase in orbital inflammation, which required immediate
      surgical intervention with postsurgical intravenous antibiotic administration.
      This case should serve to emphasize the crucial requirement for intensive
      attention to orbital symptoms after dental procedures.

PMID- 19101482
TI  - A case report: Unusual anatomy of maxillary second molar with 3 mesiobuccal
      canals.
AB  - Understanding root canal morphology is one of the most important steps in
      successful root canal treatment. Thus, during the diagnosis and treatment phases
      of the maxillary molars, a clinician must be aware that anatomical variations
      exist. A number of studies, especially in vitro, have investigated various root
      canal morphologies, including aberrations of maxillary molars. This clinical case
      report highlights an unusual variant of a maxillary second molar with a third
      mesiobuccal canal.

PMID- 19101483
TI  - Possibility of root canal preparation by Er:YAG laser.
AB  - OBJECTIVE: The purpose of this study was to evaluate the cutting efficiency and
      morphological changes of root dentin irradiated by an Er:YAG laser in vitro.
      STUDY DESIGN: Thirty-two root dentin blocks were divided into 4 groups. The
      irradiation conditions were as follows: Group 1 (G1): 30 mJ, 10 pps, 1 mm/s, 20
      times; Group 2 (G2): 30 mJ, 10 pps, 1 mm/s, 10 times; Group 3 (G3): 30 mJ, 10
      pps, 2 mm/s, 20 times; and Group 4 (G4): 30 mJ, 25 pps, 1 mm/s, 10 times. After
      being irradiated, the blocks were observed by mu-CT and their width and depth
      were measured. Moreover, SEM observations were performed. RESULTS: There were
      significant differences between G1 and G2, between G1 and G3, between G2 and G4,
      and between G3 and G4 for both width and depth (P < .05). The SEM observations
      showed that no smear layer was present on the surface of any of the samples.
      CONCLUSION: These results show that the Er:YAG laser operated under the
      conditions used in this study is an effective tool for root canal preparation.

PMID- 19101484
TI  - Incidence and relationship of an additional root in the mandibular first
      permanent molar and primary molars.
AB  - OBJECTIVES: The mandibular first permanent and primary molars occasionally have
      an additional root located distolingually. This study aimed to determine the
      incidences of an additional root in these molars and their relationship. STUDY
      DESIGN: This study involved 4050 children for whom periapical radiographs of the
      mandibular molar area were available. The incidence of an additional root for
      each molar was calculated and the pattern of concurrent additional roots in
      different molars was also investigated. RESULTS: Additional roots were present in
      33.1%, 27.8%, and 9.7% of the first permanent, second primary, and first primary
      molars, respectively. When an additional root was present in a primary molar, the
      probability of the posterior adjacent molar also having an additional root was
      greater than 94.3%. CONCLUSION: The presence of an additional root in a primary
      molar can be used to predict the presence of an additional root in molars
      posterior to it.

PMID- 19101485
TI  - The effect of master point taper on bond strength and apical sealing ability of
      different root canal sealers.
AB  - OBJECTIVE: The aim of this study was to compare the bond strength and apical
      sealing ability of master gutta-percha points with different tapers, as used in
      conjunction with different root canal sealers. STUDY DESIGN: Roots of extracted
      human maxillary incisors (n = 135) were prepared with 0.06-taper nickel-titanium
      rotary files to final size 30. The roots were then randomly divided into 3 groups
      according to the root canal sealer used: 1) AH Plus; 2) Ketac-Endo; and 3)
      EndoREZ. Each sealer was combined with 1 of the following obturation techniques:
      0.02-tapered gutta-percha master cone using lateral condensation, 0.04-tapered
      gutta-percha master cone using lateral condensation, or 0.06-tapered gutta-percha
      as a single cone. The bond strength and apical sealing ability were measured with
      the push-out test and dye penetration test, respectively. The data were
      statistically analyzed by using Kruskal-Wallis test with Bonferroni correction at
      P = .05. RESULTS: Both the taper of the gutta-percha point and root canal sealers
      had significant effects on push-out bond strength (P < .001). According to the
      microleakage data, AH Plus exhibited significantly lower overall leakage, whereas
      no difference was found between master cone points (P = .093). CONCLUSIONS: The
      use of matched-taper gutta-percha points in canals prepared with tapered rotary
      instruments may be advocated to improve bond strength ability of root canal
      filling material. Furthermore, AH Plus may be preferable to EndoRez and Ketac
      Endo in terms of improved sealing and bonding quality of filling material.

PMID- 19101486
TI  - Study of the bismuth oxide concentration required to provide Portland cement with
      adequate radiopacity for endodontic use.
AB  - OBJECTIVE: The purpose of this study was to determine the ideal concentration of
      bismuth oxide in white Portland cement to provide it with sufficient radiopacity
      for use as an endodontic material (ADA specification #57). STUDY DESIGN: 2-mm
      thick standardized test specimens of white MTA and of white Portland cement, as
      controls, and of white Portland cement with the experimental addition of 5%, 10%,
      15%, 20%, 25% or 30% of bismuth oxide were radiographed and compared with various
      thicknesses of pure aluminum, using optic density to determine the observed
      grayscale levels of radiopacity in a scale ranging from 0 to 255. The data was
      submitted to ANOVA (p<0.05) and the Ryan-Einot-Gabriel-Welch and Quiot test
      (REGWQ) for multiple comparison of the means. RESULTS: White Portland cement with
      0%, 5%, 10%, 15%, 20%, 25% and 30% of bismuth oxide presented mean readings of
      63.3, 95.7, 110.7, 142.7, 151.3, 161.0 and 180.0 respectively. MTA presented a
      mean reading of 157.3. The readings of MTA and white Portland cement with 15%
      bismuth oxide did not differ significantly from the reading observed for a
      thickness of 4 mm of aluminum (145.3), which is considered ideal for a test
      specimen by ADA specification #57 (2 mm above the thickness of the test
      specimen). CONCLUSION: White MTA and white Portland cement with 15% bismuth oxide
      presented the radiopacity required for an endodontic cement.

PMID- 19101487
TI  - Oral facial jaw mouth cosmetic implant surgeons--what's in a name?

PMID- 19101488
TI  - Licensure requirements for dental teleradiology in these "Disunited States".

PMID- 19101489
TI  - Concomitant surgical treatment of dental and valvular heart diseases.
AB  - BACKGROUND: Invasive dental procedures are often indicated before cardiac valve
      surgery. The purpose of this case-control study was to determine the risks and
      benefits of concomitant dental and thoracic surgery. METHODS: Critically ill
      cardiac inpatients requiring cardiac valve surgery were referred by the
      Department of Thoracic and Cardiovascular Surgery to our Oral Medicine consult
      service. Those requiring dental extractions were considered for dental treatment
      during the same general anesthetic as the cardiac surgery. These study patients
      were compared with control patients who had extractions before valve surgery in a
      different setting. There was no attempt to analyze the impact of this practice on
      the development of infective endocarditis. All patients received broad-spectrum
      antibiotics during dental surgery. RESULTS: Twenty-one patients had concomitant
      oral and cardiac valve surgery. Seventeen patients were in the control group.
      There were no statistically significant differences between cases and controls in
      demographics, length of stay, nature of the dental surgery, mean number of teeth
      removed, oral bleeding, or postoperative infections. One patient in the control
      group developed prosthetic valve endocarditis versus none in the concomitant
      surgery group. CONCLUSIONS: This case-control study suggests that concomitant
      surgical procedures for dental and valvular heart disease can be accomplished
      without clinically significant oral complications. Given the risk from poor oral
      health following cardiac valve surgery, this approach should be considered for
      patients who would benefit by avoiding a second general anesthetic and/or a delay
      in cardiac surgery, and by having their oral surgery performed in the safest
      environment.

PMID- 19101490
TI  - Alterations of p16 and p14ARF genes and their 9p21 locus in oral squamous cell
      carcinoma.
AB  - The p16 gene encodes a 16-kDa cyclin kinase inhibitor, and the p14ARF gene a 14
      kDa protein, which acts as a cell cycle regulator or tumor suppressor in human
      cancer cells. Both genes are mapped on chromosome 9p21. Previous studies have
      suggested that the p16 gene has important roles in head and neck squamous cell
      carcinoma. To clarify carcinogenesis in oral squamous cell carcinoma (OSCC), we
      examined 44 primary OSCCs for alterations of p16 and p14ARF mRNA expression, the
      methylation status of the p16 gene promoter, the loss of heterozygosity (LOH) at
      the 9p21 locus, and p16 and p14ARF gene mutations. Alterations of p16 and p14ARF
      mRNA expression were seen in 27 (61.4%) of 44 and 10 (22.7%) of 44 of OSCC
      samples, respectively. Methylation of the p16 gene promoter region was detected
      in 28 (63.6%) of 44 samples, and LOH at 9p21 locus was found in 30 (68.2%) of 44.
      p16 and p14ARF gene mutations were observed in 4 (9.0%) of 44 and 2 (4.5%) of 44
      samples, respectively. Suspected homozygous deletion (HD) was seen in 9 (20.5%)
      of 44. All cases except one (97.7%) showed alterations in p16, p14ARF, and their
      locus. These data indicate that the status of p16 and p14ARF genes in OSCC is
      frequently influenced by methylation, gene mutation, and allelic deletions.
      Furthermore, these genes and their 9p21 locus have various roles in the
      pathogenesis of OSCC.

PMID- 19101491
TI  - Gingival squamous cell carcinoma in adolescence.
AB  - Squamous cell carcinoma (SCC) is a rare finding in the adolescent population,
      with most cases occurring in patients with underlying heritable diseases or
      immunologic conditions. Moreover, the incidence of oral SCC in this age group is
      extremely low. While isolated cases of adolescent oral SCC have been documented,
      most have been primary tongue or lip lesions. We report 4 cases of gingival SCC
      occurring in otherwise healthy adolescent patients. The preliminary clinical
      impressions ranged from factitial injury to inflammatory tissue. Microscopic
      similarities, including overlap with pseudoepitheliomatous hyperplasia and
      keratoacanthoma, were seen. Review of the literature indicates that adolescent
      gingival SCC is extremely rare and a challenging diagnosis for the clinician and
      pathologist alike. Diagnostic pitfalls, possible etiologic factors, and the
      prognostic outlook of this condition are discussed.

PMID- 19101492
TI  - Comparative clinicopathological study of intraoral sebaceous hyperplasia and
      sebaceous adenoma.
AB  - OBJECTIVE: The objective of this study was to compare the clinicopathological
      features of oral sebaceous hyperplasia and sebaceous adenoma. STUDY DESIGN:
      Clinical data, microscopical characteristics, and ki-67 immunoexpression were
      comparatively analyzed on 2 intraoral sebaceous adenomas, 6 intraoral sebaceous
      hyperplasias, and 21 normal intraoral sebaceous glands. RESULTS: Clinically,
      sebaceous glands presented as multiple separated papules, sebaceous hyperplasias
      as a single enlarged papule, and sebaceous adenoma as a well-defined nodule.
      Microscopically, sebaceous adenoma presented an increased number of lobules,
      smaller lobules, and a greater number of germinative/squamous cells. Sebaceous
      hyperplasia also had an increased number of lobules and fewer number of
      germinative/squamous cells, as compared to normal oral sebaceous glands. Ki-67
      expression was seen only in germinative cells and counts were higher in sebaceous
      adenomas followed by hyperplasias and normal glands. CONCLUSIONS: Sebaceous
      hyperplasias and adenomas showed different clinical, microscopic, and
      proliferative characteristics, suggesting the usefulness of the studied criteria
      on diagnosis of these uncommon oral lesions.

PMID- 19101493
TI  - Image distortion and magnification of 3 digital CCD cephalometric systems.
AB  - OBJECTIVE: The magnification and distortion of images made from scanning and
      nonscanning CCD cephalometric systems was evaluated. STUDY DESIGN: Acrylic box
      and dry human skull phantoms were imaged using a conventional cephalostat, the
      nonscanning Kodak 8000C, the horizontally scanning GE/Instrumentarium OC100D, and
      the vertically scanning Sirona OrthophosDS. True linear and angular measurements
      of the phantoms were made using a coordinate measuring system and the Hitachi
      MercuRay cone beam system. The accuracy of linear and angular measurements was
      assessed, as were magnification and distortion, where appropriate. RESULTS:
      Statistically significant differences between linear and angular measurements
      were found for almost all measurements for both phantoms. In general, the
      conventional cephalostat and Sirona OrthophosDS systems produced the greatest
      magnification and distortion while the GE/Instrumentarium OC 100D and Kodak 8000C
      systems, the least. CONCLUSIONS: Measurement differences related to the beam
      geometries of these systems could not be predicted a priori. Unaccounted for,
      these differences could result in clinically significant consequences.

PMID- 19101494
TI  - Task-specific enhancement filters in storage phosphor images from the Vistascan
      system for detection of proximal caries lesions of known size.
AB  - OBJECTIVE: The aim was to compare original 8-bit images from the Vistascan
      storage phosphor plate system with images enhanced with specific filters for
      detection of proximal caries lesions and, further, to analyze the mutual
      sensitivity of the filtered images for different lesion sizes. STUDY DESIGN: One
      hundred sixty approximal noncavitated surfaces were radiographed using the
      Vistascan storage phosphor plate system. Original and enhanced (Fine, Caries1,
      and Caries2 filters) images were assessed by 6 observers who recorded the
      presence/absence of proximal carious lesions. Microscopy served to detect and
      measure true lesion size. RESULTS: One hundred one surfaces were sound, and 59
      had lesions. The sensitivity of the Fine filter images was significantly higher
      than the Caries1 and Caries2 filter modalities (P < .005). The original images
      did not differ significantly from the Caries1 and Caries2 modalities. Both the
      Fine filter and the original images had a significantly higher specificity than
      the Caries2 modality (P < .005). The overall accuracies for the Fine filter and
      the original images were significantly higher than for the Caries2 modality (P <
      .005). The Fine filter images also had higher accuracy than the Caries1 modality
      (P < .05). The mutual sensitivity of the filters varied little with lesion size.
      CONCLUSION: Fine filter may be a promising enhancement tool for images used for
      detection of shallow carious lesion, because it showed less observer variability.
      The task-specific enhancement filters, Caries1 and Caries2, were less accurate
      than the original and Fine filter images and cannot be recommended for detection
      of the lesion sizes included in this study.

PMID- 19101495
TI  - Comparison of anesthetic efficacy of 4% articaine and 2% lidocaine for maxillary
      buccal infiltration in patients with irreversible pulpitis.
AB  - OBJECTIVE: The purpose of this prospective, randomized, double-blind study was to
      compare the anesthetic efficacy of 4% articaine and 2% lidocaine (both with
      1:100,000 epinephrine) for buccal infiltration in patients experiencing
      irreversible pulpitis in maxillary posterior teeth. STUDY DESIGN: Forty patients
      with irreversible pulpitis in first premolar or first molar were divided into 4
      study groups and received buccal infiltration of either 4% articaine or 2%
      lidocaine in a double-blind manner. Endodontic access was begun 5 minutes after
      solution deposition. Success was defined as no or mild discomfort (VAS
      recordings) during the endodontic procedure. RESULTS: The success rate for
      maxillary buccal infiltration to produce pulpal anesthesia using articaine was
      100% in first premolar and first molar, and for the lidocaine solution, success
      rate was 80% in first premolar and 30% in first molar. There was high significant
      difference between the articaine and lidocaine solutions (ANOVA; P < .001).
      CONCLUSION: The efficacy of 4% articaine was superior to 2% lidocaine for
      maxillary buccal infiltration in posterior teeth.

PMID- 19101496
TI  - An immunohistochemical evaluation of cell adhesion molecules in human dental pulp
      after tooth preparation and application of temporary luting cements.
AB  - OBJECTIVE: The aim of this study was to determine if temporary luting cements
      used with provisional restorations alter the expression of cell adhesion
      molecules (CAMs) in human dental pulp. STUDY DESIGN: Twenty-five healthy human
      premolars and third molars scheduled to be extracted for orthodontic reasons were
      randomly assigned to 5 experimental groups. Group 1 included untreated teeth as
      negative control. In groups 2-5, provisional crowns were cemented to the prepared
      teeth with either eugenol-containing or eugenol-free temporary cement and
      extracted 24 or 48 h after the treatment. Expression ratio and staining intensity
      of CAMs, including E-selectin, P-selectin, intercellular adhesion molecule 1
      (ICAM-1), vascular cell adhesion molecule 1 (VCAM-1), and platelet endothelial
      cell adhesion molecule 1 (PECAM-1), was investigated in the pulp samples. The
      assessment of immunohistochemical reactions was performed by 2 independent
      observers using a semiquantitative scale. RESULTS: Significant reductions were
      recorded in the expression ratio and/or the staining intensity of E-selectin,
      ICAM-1, and VCAM-1 in samples removed 48 h after treatment with eugenol
      containing cement compared with intact teeth. This reduction was significant only
      for ICAM-1 for 48-h eugenol-free samples. Moreover, the eugenol-free cement group
      indicated considerably higher E-selectin, ICAM-1, and VCAM-1 expression compared
      with the eugenol-containing group (P < .005) 48 h after the application. The
      PECAM-1 reactivity was similar for all of the experimental groups. CONCLUSION:
      Application of temporary luting cements after tooth preparation for full crown
      causes alterations in the expression of endothelial CAMs in the dental pulp.

PMID- 19101497
TI  - Childhood uveitis-young patients, old problems, new perspectives.

PMID- 19101498
TI  - Magnetic bead-based phage anti-immunocomplex assay (PHAIA) for the detection of
      the urinary biomarker 3-phenoxybenzoic acid to assess human exposure to
      pyrethroid insecticides.
AB  - Noncompetitive immunoassays are advantageous over competitive assays for the
      detection of small molecular weight compounds. We recently demonstrated that
      phage peptide libraries can be an excellent source of immunoreagents that
      facilitate the development of sandwich-type noncompetitive immunoassays for the
      detection of small analytes, avoiding the technical challenges of producing anti
      immunocomplex antibody. In this work we explore a new format that may help to
      optimize the performance of the phage anti-immunocomplex assay (PHAIA)
      technology. As a model system we used a polyclonal antibody to 3-phenoxybenzoic
      acid (3-PBA) and an anti-immunocomplex phage clone bearing the cyclic peptide
      CFNGKDWLYC. The assay setup with the biotinylated antibody immobilized onto
      streptavidin-coated magnetic beads significantly reduced the amount of coating
      antibody giving identical sensitivity (50% saturation of the signal (SC(50))=0.2
      0.4ng/ml) to the best result obtained with direct coating of the antibody on
      ELISA plates. The bead-based assay tolerated up to 10 and 5% of methanol and
      urine matrix, respectively. This assay system accurately determined the level of
      spiked 3-PBA in different urine samples prepared by direct dilution or clean-up
      with solid-phase extraction after acidic hydrolysis with overall recovery of 80
      120%.

PMID- 19101499
TI  - Integrin inhibitors from snake venom: exploring the relationship between the
      structure and activity of RGD-peptides.
AB  - alphaIIbbeta3 is an integrin that is involved in platelet adhesion and
      aggregation. This receptor may be inhibited by cysteine-rich peptides known as
      disintegrins. We isolated two disintegrins from Bothrops jararaca venom called
      jarastatin and jararacin. We evaluated the structural characteristics and the
      effects on human platelet aggregation of these disintegrins. Inhibitory profiles
      were compared to six distinct peptides synthesized based on their RGD hairpin
      loop primary sequences. Both jarastatin and jararacin inhibited ADP and thrombin
      induction. Conversely, none of the cyclic peptides showed high-quality activity
      in assays induced by ADP or thrombin. We constructed homology models for all of
      these molecules, and theoretically evaluated their interaction with the
      alphaIIbbeta3 crystal structure using a molecular modeling approach. These
      results support the observations that the cyclic peptides had little effects, and
      also reinforce the observation that residues outside the disintegrin RGD sequence
      are required for interactions with receptor.

PMID- 19101500
TI  - Calcium inhibits diacylglycerol uptake by serum albumin.
AB  - Serum albumin is an abundant protein in blood plasma, that is well-known for its
      ability to transport hydrophobic biomolecules and drugs. Recent hypotheses
      propose that serum albumin plays a role in the regulation of lipid metabolism in
      addition to its lipid transport properties. The present work explores the
      capacity of bovine serum albumin (BSA) to extract diacylglycerols (DAG) from
      phospholipid bilayers, and the inhibition of such interaction by divalent
      cations. Quantitative measurements using radioactive DAG and morphological
      evidence derived from giant unilamellar vesicles examined by confocal microscopy
      provide concurrent results. BSA extracts DAG from vesicles consisting of
      phosphatidylinositol/DAG. Long, saturated DAG species are incorporated more
      readily than the shorter-chain or unsaturated ones. Divalent cations hinder DAG
      uptake by BSA. For Ca(2+), the concentration causing half-maximal inhibition is
      approximately 10 muM; 90% inhibition is caused by 100 muM Ca(2+). Sr(2+) requires
      concentrations one order of magnitude higher, while Mg(2+) has virtually no
      effect. As an example on how DAG uptake by BSA, and its inhibition by Ca(2+),
      could play a regulating role in lipid metabolism, a PI-specific phospholipase C
      has been assayed in the presence of BSA and/or Ca(2+). BSA activates the enzyme
      by removing the end-product DAG, but the activation is reverted by Ca(2+) that
      inhibits DAG uptake.

PMID- 19101501
TI  - Supramolecular organization of S12363-liposomes prepared with two different
      remote loading processes.
AB  - The S12363 anticancer drug was encapsulated into liposomes in an attempt to
      increase its therapeutic index. Loading of S12363 was achieved using two
      different processes based on the formation of either a pH gradient or an ammonium
      gradient between the acidic inner liposomal compartment and the basic outer
      phase. High encapsulation yields (>90%) were obtained using both processes for
      sphingomyelin/cholesterol/cholesterol-PEG vesicles. Spectrofluorimetry
      measurements have shown that liposomes were characterized by an internal pH
      around 4 for both loading processes. This internal pH was stable over a period of
      at least 20 days. Differential scanning calorimetry coupled with time-resolved
      synchrotron X-ray diffraction was used to study the drug/carrier supramolecular
      organization. In ammonium sulfate, S12363 was inserted into the bilayer in the
      vicinity of the polar headgroup. In citrate buffer, S12363 was mainly adsorbed at
      the water-lipid interface. The drug partitioning into the membrane was
      inhomogeneous and led to the formation of drug-rich and drug-poor domains. This
      effect was enhanced in the presence of cholesterol, especially in ammonium
      sulfate. To conclude, for both processes, the encapsulated drug was found inside
      the liposome aqueous core but strongly interacting with the membrane.

PMID- 19101502
TI  - Effects and underlying mechanisms of curcumin on the proliferation of vascular
      smooth muscle cells induced by Chol:MbetaCD.
AB  - Proliferation of vascular smooth muscle cells (VSMCs) contributes to the
      development of various cardiovascular diseases. Curcumin, extracted from Curcumae
      longae, has been shown a variety of beneficial effects on human health, including
      anti-atherosclerosis by mechanisms poorly understood. In the present study, we
      attempted to investigate whether curcumin has any effect on VSMCs proliferation
      and the potential mechanisms involved. Our data showed curcumin concentration
      dependently abrogated the proliferation of primary rat VSMCs induced by
      Chol:MbetaCD. To explore the underlying cellular and molecular mechanisms, we
      found that curcumin was capable of restoring caveolin-1 expression which was
      reduced by Chol:MbetaCD treatment. Moreover, curcumin abrogated the increment of
      phospho-ERK1/2 and nuclear accumulation of ERK1/2 in primary rat VSMCs induced by
      Chol:MbetaCD, which led to a suppression of AP-1 promoter activity stimulated by
      Chol:MbetaCD. In addition, curcumin was able to reverse cell cycle progression
      induced by Chol:MbetaCD, which was further supported by its down-regulation of
      cyclinD1 and E2F promoter activities in the presence of Chol:MbetaCD. Taking
      together, our data suggest curcumin inhibits Chol:MbetaCD-induced VSMCs
      proliferation via restoring caveolin-1 expression that leads to the suppression
      of over-activated ERK signaling and causes cell cycle arrest at G1/S phase. These
      novel findings support the beneficial potential of curcumin in cardiovascular
      disease.

PMID- 19101503
TI  - Phosphorylation of cyclin-dependent kinase 2 peptides enhances metal binding.
AB  - The cyclin-dependent kinase CDK2 is inactivated by phosphorylation on either of
      the two neighbouring residues Thr14 or Tyr15. The effect of phosphorylation on
      metal ion binding has been investigated with peptides incorporating residues 6-20
      of CDK2. The stoichiometry of Ca(2+) binding increased from 1 in the un- and
      singly-phosphorylated peptides to 2 in the doubly phosphorylated peptide, without
      large changes in the affinity (75-250 microM). In contrast although binding of
      ferric ions to the un-phosphorylated peptide was not detected, both singly- and
      doubly-phosphorylated peptides bound two Fe(3+) ions. Binding of Ca(2+) or Zn(2+)
      ions to the doubly phosphorylated CDK2 peptide did not cause any change in
      absorbance, but increased the affinity of the peptide for Fe(3+) ions. These
      results demonstrate that double phosphorylation of CDK2 peptides increases the
      stoichiometry of metal ion binding, and hence may contribute to the previously
      observed regulation of CDK2 activity by metal ions.

PMID- 19101504
TI  - Expression of pro-angiogenic cytokines and their inhibition by dexamethasone in
      an ex vivo model of nasal polyps.
AB  - We used an organ culture of nasal polyps (NP) to provide ex vivo model to study
      the expression of pro-angiogenic cytokines and the effect of glucocorticoids in
      the pathogenesis of NP. Glucocorticoids are the drugs of choice for clinical
      treatment of NP; however, their mechanism of action is not fully understood. The
      cell-cell and cell-matrix integrity is well maintained in cultured NP. Expression
      of IL-6, IL-8, bFGF, GRO, and MCP-1 was increased in cultured NP compared to pre
      cultured NP. Expression levels of IL-6, bFGF, and GRO in cultured NP were
      downregulated by dexamethasone (DEX) treatment, while MCP-1 expression was not
      suppressed. Further, RT-PCR and immunohistochemical analysis showed that HIF
      1alpha and VEGF were suppressed in DEX-treated NP compared to untreated NP. Taken
      together, these results suggest that ex vivo organ culture can be considered a
      useful model to study the pathogenesis and regulation of pro-angiogenic cytokines
      in nasal polypogenesis.

PMID- 19101505
TI  - Detection and chromatographic removal of lipopolysaccharide in preparations of
      multifunctional galectins.
AB  - The functional spectrum of human galectins is currently explored, with a wide
      range of activities being described. The role of galectin-3 as adhesin for
      bacteria is based on its strong binding to lipopolysaccharides (LPSs), which
      brings the possibility of such a contamination in galectin preparations to
      awareness. This assumption was verified in three independent functional assay
      systems using polymyxin B as inhibitor of LPS-dependent effects. Moreover, a
      commercial LPS quantification kit also revealed LPS in galectin preparations.
      Chromatography was effective in removing LPS, suggesting that such a technique
      needs to be applied to prevent assigning cellular responses to galectins rather
      than LPS.

PMID- 19101506
TI  - Insight into estrogenicity of phytoestrogens using in silico simulation.
AB  - Phytoestrogens, including miroestrol and deoxymiroestrol, have the ability to act
      through competition with estrogen for binding to the estrogen receptor (ER).
      Here, we utilize manual ligand docking followed by molecular dynamics simulations
      and binding free energy calculations with the linear interaction energy method to
      predict the binding modes and the binding affinities of phytoestrogens on the
      ligand binding domain of ER (ERalpha-LBD). The calculations brought about the
      good correlation between the calculated binding free energy and the bioassays.
      Furthermore, consideration of Lennard-Jones and Coulomb interaction energies of
      miroestrol and deoxymiroestrol on ERalpha-LBD provided the information to develop
      the phytoestrogen derivatives as the preferred drug for ER positive breast cancer
      treatment.

PMID- 19101507
TI  - RhoA induces expression of inflammatory cytokine in adipocytes.
AB  - Rho GTPase regulates actin cytoskeleton organization and assembly in many cell
      types, however, its significance in adipose tissue is not well characterized.
      Here, we demonstrate high RhoA activity in adipose tissues of C57BL/6J mice. To
      determine the effect of RhoA activation on 3T3-L1 cells, stable cell lines
      overexpressing G14VRhoA fused to destabilizing domain of FKBP12 (DD-G14VRhoA-L1)
      were generated. Treatment of DD-G14VRhoA-L1 cells with Shield1 following their
      differentiation into adipocytes, resulted in the appearance of thick cortical
      actin filaments, and increased the mRNA expression levels of plasminogen
      activator inhibitor type-1 (PAI-1) and monocyte chemoattractant protein-1 (MCP
      1). The induction of PAI-1 and MCP-1 was inhibited by treatment with a Rho
      associated kinase (ROCK) inhibitor, Y-27632. In 3T3-L1 adipocytes, tumor necrosis
      factor-alpha activated RhoA and increased mRNA expression of PAI-1 and MCP-1, and
      their treatment with Y-27632 partially inhibited these changes. The results
      indicate that RhoA-ROCK pathway induces inflammatory cytokine expression in
      adipocytes.

PMID- 19101508
TI  - Analysis of DNA variations in promoter region of HCNP gene with Alzheimer's
      disease.
AB  - Hippocampal cholinergic neurostimulating peptide (HCNP), which enhances
      acetylcholine synthesis and induces cholinergic phenotype development of the
      septohippocampal system, is derived from HCNP precursor protein (HCNPpp), also
      known as phosphatidylethanolamine binding protein (PEBP) and Raf kinase inhibitor
      protein (RKIP). Our previous study demonstrated that expression of HCNPpp mRNA
      was decreased in the hippocampi of autopsied brains of Alzheimer's disease (AD)
      patients, indicating the association of HCNP with the pathogenesis of AD. To
      clarify the involvement of gene variations in the promoter region of the gene
      encoding HCNPpp in this mRNA reduction, we analyzed DNA polymorphisms or
      mutations within this gene promoter region in AD patients by direct sequencing.
      The promoter was found to contain a CpG island without a TATA box, an element of
      housekeeping gene promoters. Moreover, no disease-specific polymorphisms or
      mutations were identified, suggesting that the decrease of mRNA can be ascribed
      to transcriptional or posttranscriptional changes in activity.

PMID- 19101509
TI  - Efficient labeling of mesenchymal stem cells using cell permeable magnetic
      nanoparticles.
AB  - For the purpose of successfully monitoring labeled cells, optimum labeling
      efficiency without any side effect is a prerequisite. Magnetic cellular imaging
      is a new and growing field that allows the visualization of implanted cells in
      vivo. Herein, superparamagnetic iron oxide (SPIO) nanoparticles were conjugated
      with a non-toxic protein transduction domain (PTD), identified by the authors and
      termed low molecular weight protamine (LMWP), to generate efficient and non-toxic
      cell labeling tools. The cells labeled with LMWP-SPIO presented the highest iron
      content compared to those labeled with naked SPIO and the complex of SPIO with
      poly-L-lysine, which is currently used as a transfection agent. In addition to
      the iron content assay, Prussian staining and confocal observation demonstrated
      the highest intracellular LMWP-SPIO presence, and the labeling procedure did not
      alter the cell differentiation capacity of mesenchymal stem cells. Taken
      together, cell permeable magnetic nanoparticles conjugated with LMWP can be
      suggested as labeling tools for efficient magnetic imaging of transplanted cells.

PMID- 19101510
TI  - RhoE enhances multidrug resistance of gastric cancer cells by suppressing Bax.
AB  - We have previously reported that RhoE is overexpressed in the SGC7901/VCR cell
      line. However, the potential role of RhoE in the development of multidrug
      resistance of gastric cancer is unknown. In the present study, RhoE enhanced the
      resistance of SGC7901 cells to several kinds of antitumor drugs. RhoE
      overexpression did not alter the intracellular adriamycin accumulation of SGC7901
      cells nor the expression of P-gp and MRP-1, but protected SGC7901 cells from
      vincristine-induced apoptosis. RhoE was found to downregulate the expression of
      Bax at a posttranscriptional level. Western blot revealed no effects of RhoE on
      the activities of the Caspase family of proteins. In brief, our study
      demonstrated that RhoE may promote the multidrug resistance phenotype of gastric
      cancer cells by decreasing the expression of Bax at posttranscriptional level,
      thus inhibiting vincristine-induced apoptosis.

PMID- 19101511
TI  - Bim is reversibly phosphorylated but plays a limited role in paclitaxel
      cytotoxicity of breast cancer cell lines.
AB  - The chemotherapeutic drug, paclitaxel, induces mitotic arrest and then activates
      the cellular apoptotic program. Although paclitaxel has been in clinical use for
      over 10 years for the treatment of breast, ovarian, and lung cancer, the
      molecular mechanisms of paclitaxel-induced cytotoxicity are ill defined. We
      decided to investigate the regulatory mechanism of the pro-apoptotic BH3-only
      protein Bim, which is known to play a role in paclitaxel cytotoxicity. We
      discovered that paclitaxel induces reversible phosphorylation of Bim. Bim
      initially displays enhanced phosphorylation during paclitaxel-induced mitotic
      arrest, and then undergoes de-phosphorylation as cells become apoptotic. This
      dynamic phosphorylation is dependent on mitotic checkpoint signaling. However,
      while these results suggest that reversible phosphorylation of Bim may contribute
      to the transmission of a mitotic checkpoint-to-apoptosis signal, we did not
      observe a strong correlation between Bim protein levels and cellular sensitivity
      to paclitaxel. Indeed, in contrast to the well-defined role of Bim in paclitaxel
      induced cell death in mouse model cells, our depletion studies demonstrate that
      Bim is not absolutely required for paclitaxel cytotoxicity in breast cancer cell
      lines. Clearly it is imperative to define the contribution of Bim in paclitaxel
      induced apoptosis of clinically relevant targets in order to rationally develop
      enhanced treatment strategies.

PMID- 19101512
TI  - BMP/Wnt antagonists are upregulated by dexamethasone in osteoblasts and reversed
      by alendronate and PTH: potential therapeutic targets for glucocorticoid-induced
      osteoporosis.
AB  - We used osteoblastic MC3T3-E1 cells to clarify the mechanisms by which
      dexamethasone (Dex) suppresses osteoblast function, or alendronate or parathyroid
      hormone (PTH) alleviate it. Dex (10(-7)M) increased mRNA expression of bone
      morphogenetic protein (BMP) antagonists, follistatin and Dan, and of a Wnt
      antagonist, secreted frizzled-related protein-1 (sFRP-1) and a Wnt signal
      inhibitor, axin-2, while concomitantly decreased the expression of downstream
      molecules, Runx2 mRNA and beta-catenin protein. Pretreatments with alendronate
      (10(-8)M) or human PTH-(1-34) (10(-8)M) totally or partially antagonized not only
      the Dex-induced enhancement in mRNA expression of follistatin/Dan and sFRP-1/axin
      2 but also the Dex-induced reduction in Runx2 mRNA expression and mineralization.
      These findings suggest that Dex suppresses the Wnt and BMP pathways as well as
      osteoblast function by enhancing the expression of BMP and Wnt antagonists, and
      bisphosphonate and PTH exert pharmacologic effects by canceling these processes.

PMID- 19101513
TI  - From cell protection to death: may Ca2+ signals explain the chameleonic
      attributes of the mammalian prion protein?
AB  - It is now accepted that a conformational change of the cellular prion protein
      (PrP(C)) generates the prion, the infectious agent responsible for lethal
      neurodegenerative disorders, named transmissible spongiform encephalopathies, or
      prion diseases. The mechanisms of prion-associated neurodegeneration are still
      obscure, as is the cell role of PrP(C), although increasing evidence attributes
      to PrP(C) important functions in cell survival. Such a behavioral dichotomy thus
      enables the prion protein to switch from a benign role under normal conditions,
      to the execution of neurons during disease. By reviewing data from models of
      prion disease and PrP(C)-null paradigms, which suggest a relation between the
      prion protein and Ca(2+) homeostasis, here we discuss the possibility that Ca(2+)
      is the factor behind the enigma of the pathophysiology of PrP(C). Ca(2+) features
      in almost all processes of cell signaling, and may thus tell us much about a
      protein that pivots between health and disease.

PMID- 19101514
TI  - IL-1 regulates the Cyp7a1 gene and serum total cholesterol level at steady state
      in mice.
AB  - We examined the role of hepatic interleukin (IL)-1alpha/beta in serum total
      cholesterol homeostasis using male and female IL-1-knockout (KO) mice and wild
      type (WT) mice. Serum total cholesterol level was higher in males than in females
      in WT and KO mice. The difference between sexes was closely correlated with the
      difference in gene expression level of cholesterol 7alpha-hydroxylase (Cyp7a1), a
      rate-limiting enzyme for bile acid synthesis. No significant sex difference in
      gene expression level of 3-hydroxy-3-methylglutaryl-CoA reductase, a rate
      limiting enzyme for cholesterol synthesis, was observed in WT mice.
      Interestingly, the gene expression level of hepatic Cyp7a1 was lower in KO mice
      than in sex-matched WT mice, while the serum total cholesterol level was the
      opposite. The present findings demonstrate that IL-1alpha and IL-1beta are
      positive regulators for the Cyp7a1 gene in steady-state mice and that Cyp7a1 is
      one of the factors that mediate the difference in serum total cholesterol level
      between sexes.

PMID- 19101515
TI  - Isocryptomerin, a novel membrane-active antifungal compound from Selaginella
      tamariscina.
AB  - Isocryptomerin is a biflavonoid isolated from Selaginella tamariscina used in
      traditional medicine. In this study, we investigated novel antifungal properties
      of isocryptomerin. The results indicated that isocryptomerin exerted antifungal
      activity in an energy-independent manner without remarkable hemolytic effects. To
      understand mode of action(s) of isocryptomerin, we conducted experiments on
      Candida albicans, a noted human pathogenic fungal strain. Flow cytometric
      analysis with bis-(1,3-dibutylbarbituric acid) trimethine oxonol [DiBAC(4)(3)], a
      translational membrane potential dye, regeneration test with fungal protoplasts,
      and fluorescence analysis with 1,6-diphenyl-1,3,5-hexatriene (DPH), a probe for
      membrane studies by depolarization, indicated that isocryptomerin could
      depolarize fungal plasma membrane. In conclusion, the results suggested that the
      antifungal activities of isocryptomerin might be due to its membrane-disruption
      mechanism(s).

PMID- 19101516
TI  - Pallidol, a resveratrol dimer from red wine, is a selective singlet oxygen
      quencher.
AB  - Pallidol is a naturally occurring resveratrol dimer from red wine with
      antioxidant and antifungal activities. In this report, with the use of the EPR
      spin-trapping technique, the scavenging and quenching effects of pallidol on
      reactive oxygen species (ROS) were investigated. The results demonstrated that
      pallidol showed strong quenching effects on singlet oxygen at very low
      concentrations, but it was ineffective to scavenge hydroxyl radicals or
      superoxide anions. Further kinetic study revealed that the reaction of pallidol
      with singlet oxygen had an extremely high rate constant (k(a)=1.71x10(10)).
      Therefore, pallidol is a potent and selective singlet oxygen quencher in aqueous
      systems. It may be used in singlet oxygen-mediated diseases as a pharmacological
      agent, which may contribute to the health beneficial effects of red wine.

PMID- 19101517
TI  - Neural progenitors, neurons and oligodendrocytes from human umbilical cord blood
      cells in a serum-free, feeder-free cell culture.
AB  - We have previously demonstrated that lineage negative cells (Lin(neg)) from
      umbilical cord blood (UCB) develop into multipotent cells capable of
      differentiation into bone, muscle, endothelial and neural cells. The objective of
      this study was to determine the optimal conditions required for Lin(neg) UCB
      cells to differentiate into neuronal cells and oligodendrocytes. We demonstrate
      that early neural stage markers (nestin, neurofilament, A2B5 and Sox2) are
      expressed in Lin(neg) cells cultured in FGF4, SCF, Flt3-ligand reprogramming
      culture media followed by the early macroglial cell marker O4. Early stage
      oligodendrocyte markers CNPase, GalC, Olig2 and the late-stage marker MOSP are
      observed, as is the Schwann cell marker PMP22. In summary, Lin(neg) UCB cells,
      when appropriately cultured, are able to exhibit characteristics of neuronal and
      macroglial cells that can specifically differentiate into oligodendrocytes and
      Schwann cells and express proteins associated with myelin production after in
      vitro differentiation.

PMID- 19101518
TI  - Congenital disorder of glycosylation Ia: new differentially expressed proteins
      identified by 2-DE.
AB  - Congenital disorders of glycosylation (CDG) comprise a family of inherited
      multisystemic disorders resulting from the deficiency of glycosylation pathways.
      N-glycosylation defects are classified as two biochemical and genetic established
      types, of which CDG-Ia is the most frequent. We performed 2-DE proteomic analysis
      on serum from two functional hemizygous CDG-Ia patients bearing T237M and D65Y
      missense changes. Comparative analysis of control/patient serum proteome allowed
      us to identify differential expression of 14 proteins. The most remarkable groups
      included proteins involved in immune response, coagulation mechanism and tissue
      protection against oxidative stress. The patient bearing D65Y mutation had less
      favourable clinical outcome and showed more abnormalities in the spot patterns,
      suggesting that the proteomic results might also be correlated with the phenotype
      of CDG patients. This study describes for the first time the differential
      expression of alpha(2)-macroglobulin, afamin, fibrin and fibrinogen in CDG
      disorder and shows how the proteomic approach might be useful for understanding
      its physiopathology.

PMID- 19101519
TI  - Inhibition of glycosaminoglycan incorporation influences collagen network
      formation during cartilage matrix production.
AB  - To understand cartilage degenerative diseases and improve repair procedures, we
      investigate the influence of glycosaminoglycans (GAGs) on cartilage matrix
      biochemistry and functionality. Bovine articular chondrocytes were cultured in
      alginate beads with(out) para-nitrophenyl-beta-d-xyloside (PNPX) to inhibit GAG
      incorporation into newly formed proteoglycans. As expected, GAG deposition in
      alginate beads decreased with increasing PNPX concentration. Next to GAGs,
      collagen deposition and cross-linking also decreased. In the presence of PNPX,
      GAGs and collagen were deposited further away from the chondrocyte than in the
      control and increased amounts were found in the culture medium. These changes
      resulted in decreased functional properties of the construct. We conclude that in
      our culture system, intact proteoglycans play a role in deposition of collagen
      and thus the formation of a functional matrix. The effect of less proteoglycans
      on the collagen network could explain why cartilage repair is ineffective in
      osteoarthritis and help us with development of new therapies.

PMID- 19101520
TI  - Covalent conjugation of Groucho with SUMO-1 modulates its corepressor activity.
AB  - Groucho is a corepressor that forms a macromolecular complex for its corepressor
      activity, in which HDAC1 is an essential component for the modulation of
      chromatin structure and transcriptional repression of target genes. Here, we show
      that Groucho is covalently conjugated with small ubiquitin-related modifier-1
      (SUMO-1) in vitro and in vivo. SUMO conjugations of Groucho occur at four
      different lysine residues. Substitutions of all these residues abolished
      sumoylation of Groucho and inhibited its corepressor activity. In addition,
      Groucho corepressor activity was reduced by inhibition of SUMO-1 conjugation via
      Ubc9 knockdown through expression of short-hairpin RNA against Ubc9. Furthermore,
      interactions between Groucho and HDAC1 are enhanced by sumoylation of Groucho,
      which is mediated by the SUMO-interaction motif of HDAC1. Taken together, these
      findings indicate that Groucho sumoylation increases its corepressor activity by
      enhancing the recruitment of HDAC1 to Groucho corepressor complex.

PMID- 19101521
TI  - Epithelial cell survival by activating transcription factor 3 (ATF3) in response
      to chemical ribosome-inactivating stress.
AB  - Ribotoxic stress responses lead to the expression of genes important for cellular
      homeostasis by modulating cell survival, proliferation and differentiation. ATF3
      was investigated for its modulation of the epithelial cellular integrity in
      response to mucosal ribotoxic stress. ATF3 expression was up-regulated by
      chemical agents causing ribotoxic stress such as deoxynivalenol and anisomycin in
      different types of intestinal epithelial cells. Moreover, reduction of ATF3 gene
      expression promoted ribotoxic stress-triggered programmed cell death, implicating
      a protective role of ATF3 in epithelial cell survival. Mechanistically,
      stabilization of ATF3 messenger RNA and protein played a critical role in
      maintaining enhanced levels of ATF3 production in response to the ribotoxic
      chemical agent. For ATF3 mRNA stability, p38 specific inhibitor SB203580 was the
      most efficient agent for suppression, suggesting the involvement of the p38 MAP
      kinase in ATF3 mRNA stabilization. In addition, the p38 MAP kinase as well as its
      downstream mediator glycogen synthase kinase 3beta (GSK3beta) was involved in
      ATF3 protein stabilization caused by chemical ribotoxic stress in human
      epithelial cells. As another separate signaling cascade, double-stranded RNA
      (dsRNA)-activated protein kinase (PKR) was demonstrated to translationally
      modulate ATF3 expression and contribute to the epithelial cell survival. PKR
      interference caused cells to be more susceptible to cell death caused by the
      chemical ribotoxic stress. The results of this study showed that enhanced ATF3
      production was associated with cellular defenses by maintaining the epithelial
      survival after ribotoxic mucosal insults.

PMID- 19101522
TI  - Liver X receptor modulators: effects on lipid metabolism and potential use in the
      treatment of atherosclerosis.
AB  - Liver X receptors (LXRs) are nuclear receptors that play a crucial role in
      regulating the expression of genes involved in lipid metabolism. Ligand
      activation of LXRs improves cholesterol homeostasis via multiple coordinated
      effects, and this function is likely to explain in part the protective effects of
      LXR activation on atherosclerosis reported in animal models. However, LXR
      activation may also induce undesirable side effects, such as lipogenesis and
      hypertriglyceridemia. This review discusses the potential to develop LXR
      modulators as therapeutic agents for atherosclerosis.

PMID- 19101523
TI  - Astaxanthin inhibits reactive oxygen species-mediated cellular toxicity in
      dopaminergic SH-SY5Y cells via mitochondria-targeted protective mechanism.
AB  - Astaxanthin is a powerful antioxidant that occurs naturally in a wide variety of
      living organisms. The aim of this study is to investigate the effect and the
      mechanism of astaxanthin on reactive oxygen species (ROS)-mediated apoptosis in
      dopaminergic SH-SY5Y cells. The treatment with DHA hydroperoxide (DHA-OOH) or 6
      hydroxydopamine (6-OHDA), either of which is ROS-inducing neurotoxin, led to a
      significant decrease in viable dopaminergic SH-SY5Y cells by MTT assay, whereas a
      significant protection was shown while the cells were pretreated with
      astaxanthin. Moreover, 100 nM astaxanthin pretreatment significantly inhibited
      apoptosis, mitochondrial abnormalities and intracellular ROS generation occurred
      in either DHA-OOH- or 6-OHDA-treated cells. The neuroprotective effect of
      astaxanthin is suggested to be dependent upon its antioxidant potential and
      mitochondria protection; therefore, it is suggested that astaxanthin may be an
      effective treatment for oxidative stress-associated neurodegeneration.

PMID- 19101524
TI  - Continuous intraventricular infusion of erythropoietin exerts
      neuroprotective/rescue effects upon Parkinson's disease model of rats with
      enhanced neurogenesis.
AB  - Parkinson's disease (PD) is characterized by degeneration of nigrostriatal
      dopaminergic neuronal systems. Several therapeutic tools for PD include
      medication using L-DOPA and surgeries such as deep brain stimulation are
      established. However, the therapies are considered as symptomatic therapy, but
      not basic remedy for PD and a new regenerative therapy would be desired to
      explore. In this study, the neuroprotective/rescue effects of erythropoietin
      (EPO), a well known hematopoietic hormone, on dopaminergic neurons were explored
      with neurogeneic potencies of EPO. EPO (100 IU/day) was continuously administered
      with micro-osmotic pump for a week to PD model of rats induced by intrastriatal 6
      hydroxydopamine (6-OHDA) injection with subsequent behavioral and
      immunohistochemical investigations. The number of amphetamine-induced rotations
      of EPO-treated rats significantly decreased, compared to the control rats. The
      preservation of dopaminergic neurons of EPO-treated rats were confirmed by
      tyrosine hydroxylase staining and Fluoro-Gold staining. The number of
      bromodeoxyuridine (BrdU)/polysialic acid-neural cell adhesion molecule (PSA-NCAM)
      double positive cells in the subventricular zone of EPO treated rats
      significantly increased with migratory potencies to the damaged striatum,compared
      to the control rats. Furthermore, TUNEL staining and phosphorylated Akt staining
      revealed that the neuroprotective/rescue effects of EPO might be mediated by anti
      apoptotic effects through the increase of phosphorylated Akt. These results
      suggest that continuous low dose infusion of EPO exerts neuroprotective/rescue
      effects with neurogeneic potentials. EPO might be a strong tool for PD therapy,
      although the further experiments should be added.

PMID- 19101525
TI  - Ontogeny of connexin 32 and 43 expression in the cerebral cortices of ovine
      fetuses, newborns, and adults.
AB  - Gap junctions are specialized membrane structures that mediate intercellular
      communication and facilitate passage of ions and small molecules between adjacent
      cells. Connexins comprise a multigene family of transmembrane proteins that form
      gap junctions. Connexin-32 and connexin-43 are among the most abundant connexins
      in brain and are highly expressed during development. Connexin-32 is expressed
      primarily in oligodendrocytes and connexin-43 in astrocytes in adult brain.
      However, both connexins are expressed in neurons during development. We examined
      the effects of ontogeny on connexin-32 and connexin-43 protein abundance in
      cerebral cortices of sheep during development. Western immunoblot was used to
      measure connexin-32 and connexin-43 expression in cerebral cortices of fetuses at
      60%, 80%, and 90% of gestation, in newborn lambs and adult sheep. Values were
      expressed as ratios to a single adult control cerebral cortical sample. Connexin
      32 abundance was higher (P<0.05) in cerebral cortices of fetuses at 60% of
      gestation (3.0+/-0.68, mean+/-SD), than in those at 90% of gestation (1.7+/-0.3),
      in newborn (1.8+/-0.55), and adult sheep (0.84+/-0.19), respectively. In
      contrast, connexin-43 abundance was higher (P<0.05) in cerebral cortices of
      fetuses at 90% of gestation (0.44+/-0.17), newborn (0.69+/-0.12) and adult sheep
      (1.14+/-0.13), than in those at 60% of gestation (0.05+/-0.01). We conclude that
      (1) connexin-32 and connexin-43 protein are expressed early in fetal life and
      throughout development, (2) each connexin displays a unique pattern of change
      with development, (3) connexin-43 exhibited ontogenic increases in protein
      abundance, whereas, connexin-32 exhibited reciprocal decreases in abundance late
      in fetal development, in newborn and adult sheep.

PMID- 19101526
TI  - Tacrolimus (FK506) suppresses rt-PA-induced hemorrhagic transformation in a rat
      thrombotic ischemia stroke model.
AB  - The aim of this study was to evaluate the effect of tacrolimus on recombinant
      tissue-plasminogen activator (rt-PA)-induced hemorrhagic transformation, and to
      characterize its suppressive action for hemorrhage. Thrombotic occlusion of the
      middle cerebral artery (MCA) was induced by photochemical reaction in
      spontaneously hypertensive rats, and hemorrhagic scores and brain damage were
      measured 24 h after MCA occlusion. Administration of rt-PA 3 h after MCA
      occlusion significantly worsened spontaneous hemorrhagic changes and tended to
      aggravate brain damage. Hematoma was observed in 7 of 15 rats treated with rt-PA,
      and 0 of 15 rats in the control group. Tacrolimus alone administered
      intravenously 3 h after MCA occlusion did not produce any hemorrhagic changes.
      The combined treatment of tacrolimus followed by rt-PA significantly decreased
      the incidence of hematoma and brain damage in comparison with that of the rt-PA
      treated group. Permeability of the blood-brain-barrier (BBB) detected by
      extravasations of Evans blue was investigated 6 h after MCA occlusion, as was the
      integrity of microvascular endothelial cells as determined by immunohistochemical
      assessment of the prevalence of platelet endothelial cell adhesion molecule-1
      (PECAM-1/CD31). Combined treatment of rt-PA with tacrolimus reduced the rt-PA
      induced extravasation of Evans blue and preserved CD31-positive cells in the
      ischemic hemisphere. Thus, tacrolimus was able to reduce the rt-PA-induced
      hemorrhagic transformation, which might be due to the protective effects on
      cerebral microvascular endothelial cells after thrombotic cerebral ischemia
      during the acute phase of cerebral ischemia. In conclusion, the combination of rt
      PA with tacrolimus may be useful for decreasing the risk of thrombolytic therapy.

PMID- 19101527
TI  - Oligomeric amyloid-beta(1-42) induces THP-1 human monocyte adhesion and
      maturation.
AB  - Amyloid-beta (Abeta) is a naturally occurring 40- or 42-residue peptide fragment
      with a primary role in Alzheimer's disease (AD). Aggregated Abeta accumulates as
      both dense core plaques and diffuse deposits in the brains of AD patients. Abeta
      plaques are surrounded by activated microglia, some of which are believed to be
      derived from peripheral blood monocytes that have infiltrated the central nervous
      system and differentiated into phagocytes in response to Abeta. We have modeled
      this process using THP-1 human monocytes and found Abeta(1-42) to be as effective
      as phorbol myristate acetate at differentiating THP-1 monocytes based on cell
      adhesion, fibronectin binding, CD11b cell-surface expression, and morphological
      changes. Cell adhesion studies and atomic force microscopy imaging revealed an
      inverse correlation between Abeta(1-42)-induced monocyte maturation and
      aggregation progression. Freshly reconstituted Abeta(1-42) solutions were the
      most effective, yet continued aggregation reduced, and eventually abolished, the
      ability to induce monocyte adhesion. Abeta(1-40), lower aggregation
      concentrations of Abeta(1-42), and an aggregation-restricted Abeta(1-42) L34P
      mutant had little effect on monocyte adhesion under the same conditions as
      Abeta(1-42). These findings implicated an oligomeric, but not monomeric or
      fibrillar, Abeta(1-42) aggregation species in the monocyte maturation process.
      The rapidly-formed Abeta(1-42) oligomers were distinct from Abeta-derived
      diffusible ligands which did not elicit significant THP-1 monocyte adhesion.
      These data demonstrate that a specific oligomeric Abeta(1-42) aggregation species
      can potently initiate the THP-1 monocyte maturation process.

PMID- 19101528
TI  - Ornithine carbamyltransferase is a sensitive marker for alcohol-induced liver
      injury.
AB  - BACKGROUND: Although mitochondrion-derived markers such as ornithine
      carbamyltransferase (OCT) and glutamate dehydrogenase (GLDH) have been reported
      to be good markers for alcohol-induced hepatic injury, their use has been limited
      due to the notion that mitochondrial markers are less sensitive than cytosol
      derived markers. We determined the clinical importance of mitochondrion-derived
      markers in the evaluation of alcohol-induced hepatotoxicity. METHODS: Rats were
      administered alcohol chronically (5-30% ethanol in drinking water with or without
      high fat diet feeding for 15 weeks) and hepatic damages were evaluated by serum
      OCT and GLDH, together with other liver enzymes such as alanine aminotransferase
      and aspartate aminotransferase. Hepatic content of the enzymes was also evaluated
      in the chronic ethanol feeding model to confirm whether induction of the enzyme
      in the liver reflects the serum activity. RESULTS: The serum activities of OCT
      and GLDH increased significantly by chronic ethanol feeding while other markers
      did not. Although the hepatic content of OCT and GLDH also increased, the serum
      activities did not correlate with the hepatic activities and the extent of
      increase in the liver was much less than in serum. CONCLUSIONS: Mitochondrion
      derived markers, especially OCT, appeared superior to cytosol-derived markers in
      the detection of alcohol-induced liver injury.

PMID- 19101529
TI  - Creatine-kinase MB mass: age and sex-associated reference limits in two different
      platforms that use the same method.
AB  - BACKGROUND: Recent updated NACB guidelines suggest that troponins are the
      biomarker of choice for the detection of myocardial necrosis, but the CK-MB mass
      is still considered an effective and alternative indicator when troponin assays
      are not available. The aim of the present study was to compare the reliability of
      two different analytical platforms in establishing the gender-specific 99th
      percentile for the CK-MB mass. METHODS: Serum samples collected from healthy
      subjects were investigated in two different laboratories, LAB 1 (354 subjects:
      222 men, 132 women; median age, 40 years, range 19-64 years) and LAB 2 (330
      subjects: 224 men, 106 women; median age, 41 years, range 18-71 years), in order
      to determine the CK-MB mass (microg/L) using the Access((R)) CKMB method (Beckman
      Coulter), a two-site immunoenzymatic sandwich assay, on UniCel DxI 800 (LAB 1)
      and Access((R)) 2 (LAB 2) analyzers (Beckman Coulter). The related plasma samples
      (lithium-heparin) were also evaluated in LAB 2. RESULTS: Total imprecision (CV%),
      calculated in control materials, ranged from 6.00 to 9.05 (concentration range,
      3.82-36.37) in LAB 1 and from 7.05 to 5.02 in LAB 2 (concentration range, 3.63
      34.18). A statistically significant gender-related difference (p<0.05) was found
      in the whole population studied, values in men being higher than those in women:
      median=1.86 vs 1.22; 99th percentile=7.64 vs 5.19. The median values in subjects
      aged 18-28 years (group 1) were lower than those in the other 4 groups (2-5):
      1.12 vs 1.59, vs 1.78, vs 1.95 and vs 2.03. The same age-related trend was also
      observed for CK-MB plasma values, which were comparable to those observed in the
      matched-serum samples: median 1.12 vs 1.10 (group 1), 1.45 vs 1.50, (group 5).
      CONCLUSIONS: The two different analytical platforms provide comparable results.
      The finding that CK-MB mass values are significantly higher in males than in
      females represents a relevant information, that will impact on patient
      classification when a myocardial necrosis has been suspected. Actually, however,
      numerous assays commercially available, lack of this information.

PMID- 19101530
TI  - The measurement of serum cholinesterase activities by an integration strategy
      with expanded linear ranges and negligible substrate-activation.
AB  - OBJECTIVES: To measure serum cholinesterase (SCHE) with an integration strategy.
      DESIGN AND METHODS: At 54.0 micromol/L butyrylthiolcholine, SCHE initial rates
      were calculated with 50.0 micromol/L butyrylthiolcholine and maximal rates via an
      improved integrated method if substrate consumptions within 5.0 min were over
      60%, or were determined by the classical initial rate method. RESULTS: The linear
      range was from 16 to 1560 nkat/L, and SCHE in clinic sera showed negligible
      substrate-activation. CONCLUSION: This strategy was effective.

PMID- 19101531
TI  - L-arginine as a factor increasing arginase significance in diagnosis of primary
      and metastatic colorectal cancer.
AB  - OBJECTIVE: The usefulness of simultaneous L-arginine and arginase determination
      in diagnosis of primary and metastatic colorectal cancer. METHODS: L-arginine and
      arginase were determined before and after surgery in serum from 43 patients with
      colorectal cancer (CRC), 24 with colorectal cancer liver metastasis (CRCLM), and
      39 control subjects (10 patients with non-malignant diseases and 29 healthy blood
      donors). RESULTS: Preoperative L-arginine concentration in the patient groups was
      2-fold higher, whereas arginase activity was over 3- and 6-fold higher in CRC and
      CRCLM when compared with control. The values of both parameters lowered
      significantly after surgery. The sensitivity of single parameter in CRC was 79%
      for L-arginine and 81% for arginase, and in CRCLM it was 83% for each parameter.
      The combination of L-arginine with arginase improved the sensitivity to 93% and
      100% in CRC and CRCLM, respectively. The specificity of L-arginine and arginase
      calculated for 39 subjects was 87% and 82%. CONCLUSION: Simultaneous
      determination of L-arginine and arginase increases the value of arginase itself
      in diagnosis and follow up of patients with CRC and CRCLM.

PMID- 19101532
TI  - Age-related oxidative stress modulation by smoking habit and obesity.
AB  - OBJECTIVE: To evaluate whether obesity and smoking habit may accelerate the age
      related increase of oxidative stress. METHODS: The Oxidative-INDEX, a score
      reflecting both oxidative and antioxidant counterparts, was estimated in 179
      subjects (50 males, aged 16-79 years). RESULTS: Oxidative stress results were
      elevated in obese and smoker subjects. Adjusted logistic regression analysis
      indicated obesity and smoking as independent variables for elevated Oxidative
      INDEX (odds ratio=4.8 and 3.1, respectively). Oxidative-INDEX steadily rises at a
      mean rate of 5.3% (0.017 AU) per year in the overall population, showing twice
      and three times higher annual rate increase in smokers and obese subjects.
      CONCLUSION: Our results suggest the pro-ageing effects of cigarette smoking and
      obesity by a more rapid and sharp elevation of the oxidative stress status.

PMID- 19101533
TI  - Cryopreservation of the Mediterranean mussel (Mytilus galloprovincialis)
      spermatozoa.
AB  - The effects of cryoprotectants, cooling rate and freezing on the mussel Mytilus
      galloprovincialis sperm were evaluated. At the end of each step of the
      experimental protocol, motility and fertilization ability of sperm were analyzed,
      compared to fresh semen. Five cryoprotectants were tested in their toxicity
      level: dimethylsulfoxide, ethylene glycol, 1-2 propylene glycol at 5%, 7%, 10%,
      15% and 20% concentration; glycerol and methanol at concentration of 5%, 7% and
      10%. The incubation times were 10, 20 and 30 min at 20+/-1 degrees C. Only
      dimethylsulfoxide, ethylene glycol and 1-2 propylene glycol at 5%, 7% and 10%
      were chosen for the following pre-freezing step. Five adaptation/chilling rates
      were analyzed: 10 min at 20+/-1, -2, -1, -0.5 and -0.25 degrees C/min and the
      last one was used for testing the best freezing procedure among seven gradients.
      Particularly, two rapid rates, three slow rates and two double step rates were
      conducted. Thawing results showed that M. galloprovincialis sperm are very
      sensitive to rapid pre-freezing and freezing protocols and only a slow procedure
      assured good motility and fertilization percentages.

PMID- 19101534
TI  - Plakoglobin has both structural and signalling roles in zebrafish development.
AB  - Plakoglobin, or gamma-catenin, is found in both desmosomes and adherens junctions
      and participates in Wnt signalling. Mutations in the human gene are implicated in
      the congenital heart disorder, arrhythmogenic right ventricular cardiomyopathy
      (ARVC), but the signalling effects of plakoglobin loss in ARVC have not been
      established. Here we report that knockdown of plakoglobin in zebrafish results in
      decreased heart size, reduced heartbeat, cardiac oedema, reflux of blood between
      heart chambers and a twisted tail. Wholemount in situ hybridisation shows reduced
      expression of the heart markers nkx2.5 at 24 hours post fertilisation (hpf), and
      cmlc2 and vmhc at 48 hpf, while there is lack of restriction of the valve markers
      notch1b and bmp4 at 48 hpf. Wnt target gene expression was examined by semi
      quantitative RT-PCR and found to be increased in morphant embryos indicating that
      plakoglobin is antagonistic to Wnt signalling. Co-expression of the Wnt
      inhibitor, Dkk1, rescues the cardiac phenotype of the plakoglobin morphant. beta
      catenin protein expression is increased in morphant embryos as is its
      colocalisation with E-cadherin in adherens junctions. Endothelial cells at the
      atrioventricular boundary of morphant hearts have an aberrant morphology,
      indicating problems with valvulogenesis. Morphants also have decreased numbers of
      desmosomes and adherens junctions in the intercalated discs. These results
      establish the zebrafish as a model for ARVC caused by loss of plakoglobin
      function and indicate that there are signalling as well as structural
      consequences of this loss.

PMID- 19101535
TI  - Moxonidine prevents ischemia/reperfusion-induced renal injury in rats.
AB  - Enhancement of renal sympathetic nerve activity during renal ischemia and its
      consequent effect on norepinephrine overflow from nerve endings after reperfusion
      play important roles in the development of ischemic acute kidney injury. In the
      present study, we evaluated whether moxonidine, an alpha(2)-adrenaline/I(1)
      imidazoline receptor agonist which is known to elicit sympathoinhibitory action,
      would prevent the post-ischemic renal injury. Ischemic acute kidney injury was
      induced by clamping the left renal artery and vein for 45 min followed by
      reperfusion, 2 weeks after contralateral nephrectomy. Intravenous (i.v.)
      injection of moxonidine at a dose of 360 nmol/kg to ischemic acute kidney injury
      rats suppressed the enhanced renal sympathetic nerve activity during the ischemic
      period, to a degree similar to findings with intracerebroventricular (i.c.v.)
      injection of moxonidine at a dose of 36 nmol/kg. On the other hand, suppressive
      effects of the i.v. treatment on renal venous norepinephrine overflow, renal
      dysfunction and tissue injury in the post-ischemic kidney were significantly
      greater than those elicited by the i.c.v. treatment. These results suggest that
      renoprotective effects of moxonidine on ischemic acute kidney injury probably
      result from its suppressive action on the ischemia-enhanced renal sympathetic
      nerve activity followed by norepinephrine spillover from the nerve endings of the
      post-ischemic kidney.

PMID- 19101536
TI  - Behavioural and pharmacological mechanisms of bupropion's anti-smoking effects:
      recent preclinical and clinical insights.
AB  - Ongoing studies continue to explore the behavioural and pharmacological effects
      of bupropion in smoking cessation studies and animal models of nicotine
      dependence. In the present review, the components of nicotine dependence that
      form the most likely targets of bupropion are identified within the context of an
      expanding preclinical and clinical literature regarding the anti-addictive
      properties of bupropion. Second, preclinical and clinical data that implicate
      specific pharmacological modes of action of bupropion in mediating the anti
      smoking effects of the compound are discussed. Third, it is suggested that the
      unique mixed pharmacological profile of bupropion provides (1) attenuation of the
      multiple negative consequences of withdrawal via blockade of dopamine and
      noradrenaline reuptake; (2) replacement of the reward-facilitating and subjective
      effects of nicotine via blockade of dopaminergic reuptake; (3) attenuation of the
      rewarding effects of acute nicotine by nicotinic acetylcholine receptor blockade.
      The importance of species differences in bupropion metabolism in the
      interpretation of preclinical studies is highlighted. Finally, future studies are
      suggested to address identified gaps in the knowledge: most importantly, to
      provide stronger evidence for the role of noradrenaline reuptake inhibition in
      bupropion-induced attenuation of nicotine withdrawal. Future studies aimed at
      providing more evidence for the three-fold nature of the anti-smoking effects of
      bupropion are also suggested, along with the possibility of utilizing adjunct
      therapies to improve smoking cessation rates.

PMID- 19101537
TI  - Effect of pretreatment with high-dose ulinastatin in preventing radiation-induced
      pulmonary injury in rats.
AB  - In order to develop a better management strategy for radiation-induced pulmonary
      injury, we compared the protective effect of pretreatment and aftertreatment with
      different doses of ulinastatin. Two hundred and forty female Sprague-Dawley rats
      were randomized into five groups. Group R received radiation only, groups P1 and
      P2 were pretreated with different doses of i.v. ulinastatin for 3 days pre- and 4
      days post-irradiation, and groups A1 and A2 were treated for 7 days post
      irradiation only. Rats were sacrificed at 2 h, and at 4, 8, 16, and 24 weeks post
      irradiation. The expressions of TGF-beta1, TNF-alpha, IL-6, hydroxyproline and
      laminin were determined. No adverse toxicological effects of ulinastatin
      pretreatment were observed. Mortality and ratio of fibrotic area was lowest in
      group P1(5/45; 30.6+/-3.11%, P<0.05 vs. A2). Expressions of TGF-beta1 and IL-6 in
      group P1 were significantly lowest at 4 weeks (3.01+/-0.35, 549+/-58, 32.3+/
      3.27, P<0.01), and expressions of hydroxyproline and laminin were also lowest at
      24 weeks (741+/-68 and 82.6+/-6.91, P<0.01) in comparison with other groups.
      Significant differences were observed in expression of TGF-beta1 and TNF-alpha in
      lung between group P1 and group A1 at 4 weeks (263+/-11% vs. and 187+/-9%, 189+/
      8% vs. 154+/-9%, P<0.01, P<0.05 respectively). Pretreatment with high dose
      ulinastatin resulted in a milder inflammatory response and suppressed pulmonary
      fibrosis, which may serve as a favorable management strategy.

PMID- 19101538
TI  - Inhibition of both COX-1 and COX-2 and resulting decrease in the level of
      prostaglandins E2 is responsible for non-steroidal anti-inflammatory drug (NSAID)
      dependent exacerbation of colitis.
AB  - A number of clinical studies have shown that non-steroidal anti-inflammatory
      drugs (NSAIDs) exacerbate inflammatory bowel disease; however the molecular
      mechanism whereby this occurs remains unclear. NSAIDs inhibit cyclooxygenase
      (COX), which has subtypes COX-1 and COX-2. In this study, we have examined the
      effect of various types of NSAIDs on the development of dextran sulfate sodium
      (DSS)-induced colitis, an animal model of inflammatory bowel disease. The DSS
      induced colitis was worsened by administration of non-selective NSAIDs but not by
      COX-1 or COX-2 selective inhibitors. However, administration of a combination of
      both COX-1- and COX-2-selective inhibitors exacerbated the colitis. The
      intestinal level of PGE(2) dramatically decreased in response to administration
      of COX-1- and COX-2-selective inhibitors, and exogenously administered PGE(2)
      suppressed the exacerbation of colitis by NSAIDs. The expression of mucin
      proteins, which protect the intestinal mucosa, was suppressed by non-selective
      NSAIDs and this expression was restored by PGE(2), both in vivo and in vitro.
      Intestinal mucosal cell growth was inhibited by non-selective NSAIDs and this
      cell growth was restored by PGE(2), both in vivo and in vitro. This study
      provides evidence that inhibition of both COX-1 and COX-2 and the resulting
      dramatic decrease in the intestinal level of PGE(2) is responsible for NSAID
      dependent exacerbation of DSS-induced colitis. Furthermore, expression of mucin
      proteins and intestinal mucosal cell growth seems to be involved in this
      exacerbation and its suppression by PGE(2).

PMID- 19101539
TI  - ATP release by cardiac myocytes in a simulated ischaemia model: inhibition by a
      connexin mimetic and enhancement by an antiarrhythmic peptide.
AB  - We studied the role of connexin hemichannels in the release of ATP by neonatal
      cardiac myocytes subject to ischaemic stress. Mechanical, osmotic and oxidative
      stress and changes in extracellular or intracellular Ca(2+) levels induce
      connexin hemichannels located in the plasma membrane to open and release small
      ions and molecules with signaling potential such as ATP. Since ATP release has
      been implicated in adaptation to oxygen deprivation, we studied its release by
      cardiac myocytes incubated in a custom-built hypoxia chamber for various periods.
      In a simulated ischaemia model (0.5% oxygen and 0.2 g/l glucose) a peak of ATP
      release occurred at 80 min followed by a return to steady state levels for a
      further 200 min. This peak of ATP release was not observed in myocytes subject to
      hypoxia (0.5% oxygen, 3.0 g/l glucose). ATP release in ischaemia was influenced
      by two classes of reagents that target connexins, the channel forming proteins of
      gap junctions. First, the connexin hemichannel inhibitors Gap 26 and 18a
      glycyrrhetinic acid abolished the ATP peak of release. Second, the AAP10, a
      peptide with antiarrhythmic properties markedly increased the peak of ATP release
      observed at 80 min of ischaemia and also induced a second smaller peak at 180-240
      min. ATP content of the myocytes and Cx43 phosphorylation were monitored. Since
      the release of ATP in ischaemia was abolished by connexin channel inhibitors and
      stimulated by a peptide developed to target connexins in the context of cardiac
      arrhythmia, the results suggest that nucleotide release by connexin hemichannels
      is likely to feature in the response of myocytes to ischaemic stress in the
      heart.

PMID- 19101540
TI  - Hypoxia regulates inflammatory gene expression in endothelial cells.
AB  - Hypoxia can activate the endothelium toward a pro-inflammatory phenotype and
      enhance leukocyte adhesion. This process is involved in pathological conditions
      such as vascular remodeling or ischemia-reperfusion injury. This study was aimed
      to obtain a global picture of the response of the endothelial cells to hypoxia
      with respect to inflammatory genes. To this purpose, we used a low density DNA
      microarray specifically designed to quantitate the expression of genes involved
      in the inflammatory pathways and a customized real-time PCR array. The expression
      of several pro-inflammatory genes known to be NF-kB target genes was decreased
      after the incubation of endothelial cells under hypoxia. In parallel, a decrease
      in the DNA binding activity of this transcription factor was observed. On the
      other hand, HIF-1 DNA binding activity was increased as well as the expression of
      several genes known to be regulated by this factor. Among them are several pro
      inflammatory genes whose overexpression could account for the increase in
      leukocyte adhesion to the hypoxic endothelial cells. We concluded that hypoxia
      does not shift the endothelial cell phenotype to a more pro-inflammatory one
      probably because of a decrease in the expression of several cytokines. On the
      other hand, a clear response to hypoxia was observed with HIF-1 probably playing
      an important role in this process.

PMID- 19101541
TI  - Plasma membrane removal in rat skeletal muscle fibers reveals caveolin-3 hot
      spots at the necks of transverse tubules.
AB  - Caveolin-3, the muscle-specific isoform of the caveolae-associated protein
      caveolin, is often thought to be localized exclusively in the surface membrane in
      mature fibers and associated with transverse (t)-tubular system only transiently
      during development. Skeletal muscle fibers present a model where the surface
      membrane (sarcolemma) can be completely separated from the cell by mechanical
      dissection. Western blotting of matching portions of individual fibers from adult
      rat muscle in which the sarcolemma was either removed (skinned segment), or left
      in place (intact segment), revealed that > or = 70% of caveolin-3 is actually
      located deeper in the fiber rather than in the sarcolemma itself. Triton
      solubility of caveolin-3 was no different between sarcolemmal and t-tubule
      compartments. Confocal immunofluorescence microscopy showed caveolin-3 present
      throughout the t-system in adult fibers, with 'hot-spots' at the necks of the
      tubules in the sub-sarcolemmal space. A similar representation was seen for the
      muscle specific voltage-dependent sodium channel Nav1.4 and it was found that at
      least some Nav1.4 co-immunoprecipitated with caveolin-3 in skinned muscle fibers.
      The caveolin-3 hot-spots just inside the opening of t-tubules may form regions
      that localize ion channels and kinases at the key place needed for efficient
      electrical transmission into the t-tubules as well as for other signaling
      processes.

PMID- 19101542
TI  - Cbf11 and Cbf12, the fission yeast CSL proteins, play opposing roles in cell
      adhesion and coordination of cell and nuclear division.
AB  - The CSL (CBF1/RBP-Jkappa/Suppressor of Hairless/LAG-1) family is comprised of
      transcription factors essential for metazoan development, mostly due to their
      involvement in the Notch receptor signaling pathway. Recently, we identified two
      novel classes of CSL genes in the genomes of several fungal species, organisms
      lacking the Notch pathway. In this study, we characterized experimentally cbf11+
      and cbf12+, the two CSL genes of Schizosaccharomyces pombe, in order to elucidate
      the CSL function in fungi. We provide evidence supporting their identity as
      genuine CSL genes. Both cbf11+ and cbf12+ are non-essential; they have distinct
      expression profiles and code for nuclear proteins with transcription activation
      potential. Significantly, we demonstrated that Cbf11 recognizes specifically the
      canonical CSL response element GTGA/GGAA in vitro. The deletion of cbf11+ is
      associated with growth phenotypes and altered colony morphology. Furthermore, we
      found that Cbf11 and Cbf12 play opposite roles in cell adhesion, nuclear and cell
      division and their coordination. Disturbed balance of the two CSL proteins leads
      to cell separation defects (sep phenotype), cut phenotype, and high-frequency
      diploidization in heterothallic strains. Our data show that CSL proteins operate
      in an organism predating the Notch pathway, which should be of relevance to the
      understanding of (Notch-independent) CSL functions in metazoans.

PMID- 19101543
TI  - Matricellular proteins in the trabecular meshwork.
AB  - The trabecular meshwork is one of the primary tissues of interest in the normal
      regulation and dysregulation of intraocular pressure (IOP) that is a causative
      risk factor for primary open-angle glaucoma. Matricellular proteins generally
      function to allow cells to modulate their attachments with and alter the
      characteristics of their surrounding extracellular matrix (ECM). In non-ocular
      tissues, matricellular proteins generally increase fibrosis. Since ECM turnover
      is very important to the outflow facility, matricellular proteins may have a
      significant role in the regulation of IOP. The formalized study of matricellular
      proteins in trabecular meshwork is in its infancy. SPARC, thrombospondins-1 and 
      2, and tenascins-C and -X, and osteopontin have been localized to varying areas
      within the trabecular meshwork. Preliminary evidence indicates that SPARC and
      thrombospondin-1 play a role in the regulation of IOP and possibly the
      pathophysiology of glaucoma. These data show promise that matricellular proteins
      are involved in IOP dysregulation and are potential therapeutic targets. Further
      study is needed to clarify these roles.

PMID- 19101544
TI  - GABA agonists fail to protect the retina from ischemia-reperfusion injury.
AB  - The purpose of this study was to test the hypothesis that ischemia/reperfusion
      injury in the rat retina may be ameliorated by reducing retinal metabolism with
      either hypothermia or inhibitory GABA agonists. The intraocular pressure of each
      right eye in rats was raised to 130 mm Hg for 60 min with the left eye serving as
      normal control. The rats were divided into four groups in terms of drug and
      hypothermia treatment: (1) Untreated ischemia, (2) Hypothermia, (3)
      Baclofen/midazolam and (4) Baclofen/muscimol. Electroretinogram was recorded
      before ischemia and again after 10-day reperfusion. Histological analysis with
      H&E staining and cell counts was performed. Untreated ischemia/reperfusion
      resulted in severely reduced ERG responses. The ERG b-wave was reduced from 423+/
      144 microV to 130+/-91 microV (mean+/-SD, n=5). With hypothermia the ERG b-wave
      was reduced from 499+/-80 microV to 237+/-111 microV (n=4). With combinations of
      baclofen and midazolam the ERG b-wave was reduced from 432+/-96 microV to 104+/
      67 microV (n=7). In baclofen/muscimol treated eyes the ERG b-wave went from 426+/
      101 microV to 148+/-118 microV (n=6). The histological tissue damage was severe
      in untreated ischemia and the baclofen/midazolam and baclofen/muscimol groups,
      but less severe in the hypothermia group. The GABA agonists do not provide any
      protection in our ischemia/reperfusion model. Our results are consistent with
      earlier reports that hypothermia may be helpful in ischemic conditions in the
      retina.

PMID- 19101545
TI  - Fasciola gigantica: cercarial shedding pattern from Lymnaea natalensis after long
      term exposure to cadmium at different temperatures.
AB  - Little is known about the response of Fasciola spp., inside its snail host to
      pollutant toxicity. The effect of long-term exposure of Lymnaea natalensis to 0.1
      microg/l, 10 microg/l, or 100 microg/l cadmium (Cd) on the infection rates with
      F. gigantica, percentage of cercariae-shedding snails and cercariae shedding
      pattern was investigated. The snails were exposed to Cd for 7 days either pre
      infection with single Fasciola miracidium or during the late pre-patent period of
      the infection. The possible interaction between metal exposure and
      acclimatization temperature was also studied in three ranges; 16-18 degrees C, 23
      25 degrees C and 30-32 degrees C. Results clearly showed that host exposure to
      100 microg/l Cd significantly affected the pattern of Fasciola development inside
      its snail host, and that the acclimatization temperature was a key factor
      affecting the role played by Cd. Pre-infection exposure to Cd caused a
      significant reduction in the infection rates where the effect was temperature
      dependent. Post-infection exposure to Cd significantly increased the percentage
      of cercariae-shedding snails; the effect was temperature-independent.
      Interestingly, post-infection exposure significantly altered the differential
      cercarial output pattern, while no clear impact on the total was found. The
      alteration in the differential cercarial output was represented as a
      significantly higher proportion of floating metacercaria as compared to fixed
      ones and also higher proportion of dead cercariae which may directly reduce the
      transmission of Fasciola to the final host. The mechanisms of cadmium impact are
      briefly discussed.

PMID- 19101546
TI  - Depletion of SK1 channel subunits leads to constitutive insulin secretion.
AB  - In the pancreas, the role of the small-conductance, calcium-activated SK channels
      remains controversial. Here, we show that three SK subtypes are expressed in the
      rat insulinoma cells. Our findings demonstrate that rat SK1 (rSK1) channels
      ensure appropriate insulin secretion by establishing the cell's negative resting
      membrane potential and shortening the duration of the action potential. We also
      found that the depletion of rSK1 transcripts generated a condition in which beta
      cells constitutively secrete insulin, even in the absence of a stimulating
      molecule (such as glucose). Together, these results implicate SK1 subunits as key
      regulators of excitability and endocrine function in beta cells.

PMID- 19101547
TI  - Elimination of a bacterial pore-forming toxin by sequential endocytosis and
      exocytosis.
AB  - Staphylococcus aureus alpha-toxin is the archetype of bacterial pore forming
      toxins and a key virulence factor secreted by the majority of clinical isolates
      of S. aureus. Toxin monomers bind to target cells and oligomerize to form small
      beta-barrel pores in the plasma membrane. Many nucleated cells are able to repair
      a limited number of lesions by unknown, calcium-independent mechanisms. Here we
      show that cells can internalize alpha-toxin, that uptake is essential for
      cellular survival, and that pore-complexes are not proteolytically degraded, but
      returned to the extracellular milieu in the context of exosome-like structures,
      which we term toxosomes.

PMID- 19101548
TI  - Proof of function of a putative 3-hydroxyacyl-acyl carrier protein dehydratase
      from higher plants by mass spectrometry of product formation.
AB  - The predicted mature portion of a putative 3-hydroxyacyl-ACP dehydratase (DH)
      from Arabidopsis was linked to an N-terminal poly-histidine-tag and the fusion
      protein expressed in Escherichia coli. Soluble dehydratase was present on
      induction at 25 degrees C and pure dehydratase eluted from a nickel-affinity
      column in 0.2-0.5M imidazole. High concentrations of imidazole were necessary to
      retain enzyme solubility. The dehydratase reaction is reversible and 3
      hydroxybutyryl- and 2-butenoyl-ACP substrates were prepared from E. coli apo-ACP.
      Analysis of these suggested contamination of apo-ACP with dehydratase and an
      additional reverse-phase chromatographic step was required during acyl carrier
      protein (ACP) preparation. Activity of purified dehydratase was demonstrated by
      mass spectrometry using 2-butenoyl-ACP, providing the first functional
      experimental evidence for plant DH gene sequences.

PMID- 19101549
TI  - Distinct gate conformations of the ABC transporter BtuCD revealed by electron
      spin resonance spectroscopy and chemical cross-linking.
AB  - BtuCD is a type II ABC importer that catalyzes the translocation of vitamin B12
      from the periplasm into the cytoplasm of Escherichia coli. Crystal structures of
      BtuCD and the related HiF (or Hi1470/71) protein from Haemophilus influenzae have
      revealed distinct conformations of the transmembrane domains that form inner and
      outer gates. We used electron spin resonance spectroscopy to study the reaction
      cycle of BtuCD after labeling the protein at residues located at these gates. The
      results suggest that BtuCD as a prototype type II ABC importer may have a
      mechanism that is distinct from that of ABC exporters such as Sav1866 or type I
      ABC importers such as those specific for molybdate (ModBC) or maltose (MalFGK).

PMID- 19101550
TI  - Characterization of chemoreceptive protein binding to an oviposition stimulant
      using a fluorescent micro-binding assay in a butterfly.
AB  - A native female-specific chemoreceptive protein of a swallowtail butterfly
      [oviposition stimulant binding protein (OSBP)] was shown to specifically bind to
      aristolochic acid, a main stimulant for oviposition from its host plant.
      Oviposition stimulants are recognized by chemoreceptive organs of insects. OSBP
      isolated previously from the chemoreceptive organs was assumed to bind to an
      oviposition stimulant. Using a highly sensitive fluorescent micro-binding assay,
      we clarified OSBP bound to aristolochic acid. Three-dimensional molecular
      modeling revealed the structure of the OSBP-aristolochic acid complex. This is
      the first report of a native chemoreceptive protein binding to an oviposition
      stimulant as a ligand in insects.

PMID- 19101551
TI  - Glutathione redox regulates TGF-beta-induced fibrogenic effects through Smad3
      activation.
AB  - Transforming growth factor-beta (TGF-beta) plays a pivotal role in the fibrogenic
      action involved in the induction of connective tissue growth factor (CTGF),
      extracellular matrix and fibroblast transformation. Smad3 mediates TGF-beta
      signaling related to the fibrotic response. In human lung fibroblasts or
      bronchial smooth muscle cells, we demonstrated that an increase in the
      intracellular glutathione level suppressed TGF-beta1-induced phosphorylation of
      Smad3, while inhibiting TGF-beta1-induced expressions of CTGF, collagen type1,
      fibronectin and transformation into myofibroblasts, which are characterized by
      the expression of alpha-smooth muscle actin. These data indicate that the
      intracellular glutathione redox status regulates TGF-beta-induced fibrogenic
      effects through Smad3 activation.

PMID- 19101552
TI  - UCP3 overexpression neutralizes oxidative stress rather than nitrosative stress
      in mouse myotubes.
AB  - The deleterious effects of oxidants on proteins may be modified by overexpression
      of uncoupling protein 3 (UCP3) in skeletal muscle cells exposed to hyperoxia or
      H(2)O(2). UCP3 overexpression significantly attenuated the increase in protein
      carbonylation in response to hyperoxia and H(2)O(2) exposures. However,
      antioxidant enzyme content and activity (superoxide dismutases, peroxiredoxins,
      glutathione peroxidase-I, and catalase) were reduced or not modified in UCP3
      overexpressing myotubes exposed to oxidants. Protein nitration increased in UCP3
      overexpressing cells exposed to hyperoxia, but not to H(2)O(2). We conclude that
      protein oxidation rather than nitration is neutralized by UPC3 overexpression in
      mouse myotubes exposed to abundant reactive oxygen species.

PMID- 19101553
TI  - The C-terminal of CysM from Mycobacterium tuberculosis protects the aminoacrylate
      intermediate and is involved in sulfur donor selectivity.
AB  - A new crystal structure of the dimeric cysteine synthase CysM from Mycobacterium
      tuberculosis reveals an open and a closed conformation of the enzyme. In the
      closed conformation the five carboxy-terminal amino acid residues are inserted
      into the active site cleft. Removal of this segment results in a decreased
      lifetime of the alpha-aminoacrylate reaction intermediate, an increased
      sensitivity to oxidants such as hydrogen peroxide, and loss of substrate
      selectivity with respect to the sulfur carrier thiocarboxylated CysO. These
      results highlight features of CysM that might be of particular importance for
      cysteine biosynthesis under oxidative stress in M. tuberculosis.

PMID- 19101554
TI  - Atomic structure of mutant PPARgamma LBD complexed with 15d-PGJ2: novel
      modulation mechanism of PPARgamma/RXRalpha function by covalently bound ligands.
AB  - 15-deoxy-Delta(12,14)-prostaglandin J(2) (15d-PGJ(2)) activates a nuclear
      receptor heterodimer, peroxisome proliferators-activated receptor gamma
      (PPARgamma)/ retinoid X receptor (RXRalpha) through covalent binding to Cys285 in
      PPARgamma ligand-binding domain (LBD). Here, we present the 1.9A crystal
      structure of C285S mutant LBD complexed with 15d-PGJ(2), corresponding to the non
      covalently bound state. The ligand lies adjacent to a hydrogen-bond network
      around the helix H2 and the nearby beta-sheet. Comparisons with previous
      structures clarified the relationships between PPARgamma function and
      conformational alterations of LBD during the process of covalently binding
      ligands, such as 15d-PGJ(2), and thus suggested a mechanism, by which these
      ligands modulate PPARgamma/RXRalpha function through conformational changes of
      the loop following helix H2' and the beta-sheet.

PMID- 19101555
TI  - A novel, anaerobically induced ferredoxin in Chlamydomonas reinhardtii.
AB  - We have found the transcript of one of at least six ferredoxin encoding genes of
      the green alga Chlamydomonas reinhardtii, FDX5, strongly accumulating in
      anaerobiosis, indicating a vital role of the encoded protein in the anaerobic
      metabolism of the cells. According to absorption and electron paramagnetic
      resonance spectroscopy, Fdx5 is a plant-type [2Fe2S]-ferredoxin with a redox
      potential similar to that of the ferredoxin PetF. However, although Fdx5 seems to
      be located in the chloroplast, it is not able to photoreduce nicotinamide adenine
      dinucleotide phosphate (NADP(+)) via ferredoxin-NADP-reductase, nor to be an
      electron donor to the plastidic [FeFe]-hydrogenase HydA1. Thus, Fdx5 seems to
      have a special role in a yet to be identified anaerobic pathway.

PMID- 19101556
TI  - Physical and functional interactions between hnRNP K and PRMT family proteins.
AB  - The mechanism underlying the protein-protein interaction of hnRNP K and PRMT
      family proteins is unclear. We examined and confirmed the arginine methylation of
      hnRNP K protein by PRMT1, not CARM1, via their direct binding. We also studied
      hnRNP K protein complexes containing CARM1, as well as PRMT1, using co
      immunoprecipitation analysis. PRMT family proteins might be involved in the
      regulation of hnRNP K functions in nuclear receptor coactivator, transactivation,
      and p21 gene and protein expressions. We believe these observations will help
      provide insights into the regulation of hnRNP K protein functions via the
      recruitment of its associated proteins, including its arginine methylation
      modifying proteins.

PMID- 19101557
TI  - A magnetic resonance spectroscopy study of brain glutamate in a model of
      plasticity in human pharyngeal motor cortex.
AB  - BACKGROUND & AIMS: Coordinated delivery of peripheral and cortical stimuli
      (paired associative stimulation [PAS]) has been shown to induce plasticity in
      limb motor cortex, however, its application in pharyngeal motor cortex and the
      molecular mechanisms involved in human neuroplasticity remain uncertain. Because
      neuroplasticity appears to form the basis for functional recovery of digestive
      functions such as swallowing after brain injury, the aim of this study was to
      characterize the induction of cortical plasticity in human pharyngeal motor
      cortex through PAS applied to pharyngeal musculature and investigate the
      potential role of glutamate in this process. METHODS: Fifteen healthy volunteers
      completed a series of experiments in which cortical excitability was assessed
      through pharyngeal motor evoked potential amplitudes in response to transcranial
      magnetic stimulation. The optimal parameters and interhemispheric interactions of
      PAS in the bilaterally represented pharyngeal system initially were investigated.
      Cortical glutamate after PAS then was assessed with magnetic resonance
      spectroscopy. RESULTS: The greatest increase in cortical pharyngeal excitability
      was seen if paired stimuli were separated by 100 ms (F[15,210] = 2.28; P < or =
      .05). Cortical excitability increased over 2 hours with analogous albeit lesser
      changes in the contralateral hemisphere. A focal and transient reduction in
      glutamate was found in the stimulated pharyngeal motor cortex (F[1,12] = 21.9; P
      = .001), without changes in any other measured brain metabolites. CONCLUSIONS:
      This study shows that PAS-induced plasticity in the human pharyngeal motor system
      is both timing- and hemisphere-dependent and provides novel evidence for the
      potential role of glutamate in modulating this effect.

PMID- 19101558
TI  - Predictive factors for early HBeAg seroconversion in acute exacerbation of
      patients with HBeAg-positive chronic hepatitis B.
AB  - BACKGROUND & AIMS: This study aimed to identify the predictors for early
      hepatitis B e antigen (HBeAg) seroconversion following acute exacerbation (AE) in
      patients with HBeAg-positive chronic hepatitis B (CHB). METHODS: A total of 151
      patients with HBeAg-positive CHB and AE were consecutively enrolled. AE was
      defined as an elevation of alanine aminotransferase level to more than 5 times
      the upper limit of normal and more than twice the patients' baseline value. Early
      HBeAg seroconversion was defined as HBeAg loss and the appearance of hepatitis B
      e antibody within 6 months of AE. Clinical and laboratory data were compared
      between an early HBeAg seroconversion group and a nonearly HBeAg seroconversion
      group. RESULTS: All patients had genotype C hepatitis B virus (HBV). Early HBeAg
      seroconversion occurred in 35.5% (39/110). Under univariate analysis, age,
      transmission mode, disease status, and serum HBV DNA level were associated with
      early HBeAg seroconversion. Multivariate analysis showed that nonvertical
      transmission mode (RR, 3.681; 95% CI, 1.279-10.592; P = .016) and low serum HBV
      DNA levels (< or = log [copies/mL]; RR, 6.891; 95% CI, 2.165-21.935; P = .001)
      were independent predictors. CONCLUSIONS: Patients with CHB with genotype C may
      have a higher chance of early HBeAg seroconversion after AE in the context of
      nonvertical transmission and/or had low serum HBV DNA levels (< or = 7 log
      [copies/mL]) at AE. Therefore, we should take into account transmission modes and
      serum HBV DNA levels when choosing appropriate management strategies for patients
      who exhibit AE of HBeAg-positive CHB with genotype C.

PMID- 19101560
TI  - Larval feeding substrate and species significantly influence the effect of a
      juvenile hormone analog on sexual development/performance in four tropical
      tephritid flies.
AB  - The juvenile hormone (JH) analog methoprene reduces the amount of time it takes
      laboratory-reared Anastrepha suspensa (Caribbean fruit fly) males to reach sexual
      maturity by almost half. Here, we examined if methoprene exerted a similar effect
      on four other tropical Anastrepha species (Anastrepha ludens, Anastrepha obliqua,
      Anastrepha serpentina and Anastrepha striata) reared on natural hosts and
      exhibiting contrasting life histories. In the case of A. ludens, we worked with
      two populations that derived from Casimiroa greggii (ancestral host, larvae feed
      on seeds) and Citrus paradisi (exotic host, larvae feed on pulp). We found that
      the effects of methoprene, when they occurred, varied according to species and,
      in the case of A. ludens, according to larval host. For example, in the case of
      the two A. ludens populations the effect of methoprene on first appearance of
      male calling behavior and number of copulations was only apparent in flies
      derived from C. greggii. In contrast, males derived from C. paradisi called and
      mated almost twice as often and females started to lay eggs almost 1 day earlier
      than individuals derived from C. greggii, but in this case there was no
      significant effect of treatment (methoprene) only a significant host effect.
      There were also significant host and host by treatment interactions with respect
      to egg clutch size. A. ludens females derived from C. paradisi laid significantly
      more eggs per clutch and total number of eggs than females derived from C.
      greggii. With respect to the multiple species comparisons, the treatment effect
      was consistent for A. ludens, occasional in A. serpentina (e.g., calling by
      males, clutch size), and not apparent in the cases of A. obliqua and A. striata.
      Interestingly, with respect to clutch size, in the cases of A. ludens and A.
      serpentina, the treatment effect followed opposite directions: positive in the
      case of A. ludens and negative in the case of A. serpentina. We center our
      discussion on two hypotheses (differential physiology and larval-food), and also
      interpret our results in light of the life history differences exhibited by the
      different species we compared.

PMID- 19101559
TI  - Premarin improves memory, prevents scopolamine-induced amnesia and increases
      number of basal forebrain choline acetyltransferase positive cells in middle-aged
      surgically menopausal rats.
AB  - Conjugated equine estrogen (CEE) is the most commonly prescribed estrogen
      therapy, and is the estrogen used in the Women's Health Initiative study. While
      in-vitro studies suggest that CEE is neuroprotective, no study has evaluated
      CEE's effects on a cognitive battery and brain immunohistochemistry in an animal
      model. The current experiment tested whether CEE impacted: I) spatial learning,
      reference memory, working memory and long-term retention, as well as ability to
      handle mnemonic delay and interference challenges; and, II) the cholinergic
      system, via pharmacological challenge during memory testing and ChAT
      immunoreactive cell counts in the basal forebrain. Middle-aged ovariectomized
      (Ovx) rats received chronic cyclic injections of either Oil (vehicle), CEE-Low
      (10 microg), CEE-Medium (20 microg) or CEE-High (30 microg) treatment. Relative
      to the Oil group, all three CEE groups showed less overnight forgetting on the
      spatial reference memory task, and the CEE-High group had enhanced platform
      localization during the probe trial. All CEE groups exhibited enhanced learning
      on the spatial working memory task, and CEE dose-dependently protected against
      scopolamine-induced amnesia with every rat receiving the highest CEE dose
      maintaining zero errors after scopolamine challenge. CEE also increased number of
      ChAT-immunoreactive neurons in the vertical diagonal band of the basal forebrain.
      Neither the ability to remember after a delay nor interference, nor long-term
      retention, was influenced by the CEE regimen used in this study. These findings
      are similar to those reported previously for 17 beta-estradiol, and suggest that
      CEE can provide cognitive benefits on spatial learning, reference and working
      memory, possibly through cholinergic mechanisms.

PMID- 19101561
TI  - Mesenchymal stem cells improve outcomes of cardiopulmonary resuscitation in
      myocardial infarcted rats.
AB  - We hypothesized that administration of allogeneic bone marrow mesenchymal stem
      cells (MSCs) by intravenous, intraventricular or intramyocardial injection could
      improve myocardial function after survival time after cardiopulmonary
      resuscitation in myocardial infarcted rats. Myocardial infarction was induced by
      ligation of the left anterior descending artery in 54 rats (6 groups, 9 rats for
      each group). Left ventricular remodeling was quantitated weekly by ejection
      fraction (EF) measurement. One month after ligation, animals were randomized to
      receive injection of either MSCs 5x10(6) labeled with PKH26 in phosphate buffer
      solution (PBS) or PBS alone as a placebo. MSCs or PBS were administered by
      injection into the right femoral vein, the left ventricular cavity, or into the
      infracted anterior ventricular free wall. Four weeks after MSC or PBS injection,
      ventricular fibrillation (VF) was induced and untreated for 6 min, followed by 6
      min of CPR prior to defibrillation. Hemodynamics, including cardiac index (CI),
      left ventricular dP/dt40 (dP/dt40), left ventricular negative dP/dt (-dP/dt) and
      left ventricular diastolic pressure (LVDP) were measured at baseline and hourly
      following return of spontaneous circulation (ROSC). Labeled MSCs were observed in
      5 microm sections obtained with a cryostat from each harvested heart.
      Independently of the site of injection of MSCs, EF, CI, dP/dt40, -dP/dt, and LVDP
      were significantly improved and sustained before and after CPR in the animals
      treated with MSCs and were associated with significantly increased survival time
      when compared with the corresponding PBS treated animals.

PMID- 19101563
TI  - The universal stress protein UspC scaffolds the KdpD/KdpE signaling cascade of
      Escherichia coli under salt stress.
AB  - The sensor kinase KdpD and the response regulator KdpE control induction of the
      kdpFABC operon encoding the high-affinity K(+)-transport system KdpFABC in
      response to K(+) limitation or salt stress. Under K(+) limiting conditions the
      Kdp system restores the intracellular K(+) concentration, while in response to
      salt stress K(+) is accumulated far above the normal content. The kinase activity
      of KdpD is inhibited at high concentrations of K(+), so it has been puzzling how
      the sensor can be activated in response to salt stress. Here, we demonstrate that
      the universal stress protein UspC acts as a scaffolding protein of the KdpD/KdpE
      signaling cascade by interacting with a Usp domain in KdpD of the UspA subfamily
      under salt stress. Escherichia coli encodes three single domain proteins of this
      subfamily, UspA, UspC, and UspD, whose expression is up-regulated under various
      stress conditions. Among these proteins only UspC stimulated the in vitro
      reconstructed signaling cascade (KdpD-->KdpE-->DNA) resulting in phosphorylation
      of KdpE at a K(+) concentration that would otherwise almost prevent
      phosphorylation. In agreement, in a DeltauspC mutant KdpFABC production was down
      regulated significantly when cells were exposed to salt stress, but unchanged
      under K(+) limitation. Biochemical studies revealed that UspC interacts
      specifically with the Usp domain in the stimulus perceiving N-terminal domain of
      KdpD. Furthermore, UspC stabilized the KdpD/KdpE~P/DNA complex and is therefore
      believed to act as a scaffolding protein. This study describes the stimulation of
      a bacterial two-component system under distinct stress conditions by a
      scaffolding protein, and highlights a new role of the universal stress proteins.

PMID- 19101562
TI  - Stable protein, unstable plaque?

PMID- 19101564
TI  - Analysis of flavivirus NS5 methyltransferase cap binding.
AB  - The flavivirus 2'-O-nucleoside N-terminal RNA methyltransferase (MTase) enzyme is
      responsible for methylating the viral RNA cap structure. To increase our
      understanding of the mechanism of viral RNA cap binding we performed a detailed
      structural and biochemical characterization of the guanosine cap-binding pocket
      of the dengue (DEN) and yellow fever (YF) virus MTase enzymes. We solved an
      improved 2.1 A resolution crystal structure of DEN2 Mtase, new 1.5 A resolution
      crystal structures of the YF virus MTase domain in apo form, and a new 1.45 A
      structure in complex with guanosine triphosphate and RNA cap analog. Our
      structures clarify the previously reported DEN MTase structure, suggest novel
      protein-cap interactions, and provide a detailed view of guanine specificity.
      Furthermore, the structures of the DEN and YF proteins are essentially identical,
      indicating a large degree of structural conservation amongst the flavivirus
      MTases. Guanosine triphosphate analog competition assays and mutagenesis
      analysis, performed to analyze the biochemical characteristics of cap binding,
      determined that the major interaction points are (i) guanine ring via pi-pi
      stacking with Phe24, N1 hydrogen interaction with the Leu19 backbone carbonyl via
      a water bridge, and C2 amine interaction with Leu16 and Leu19 backbone carbonyls;
      (ii) ribose 2' hydroxyl interaction with Lys13 and Asn17; and (iii) alpha
      phosphate interactions with Lys28 and Ser215. Based on our mutational and analog
      studies, the guanine ring and alpha-phosphate interactions provide most of the
      energy for cap binding, while the combination of the water bridge between the
      guanine N1 and Leu19 carbonyl and the hydrogen bonds between the C2 amine and
      Leu16/Leu19 carbonyl groups provide for specific guanine recognition. A detailed
      model of how the flavivirus MTase protein binds RNA cap structures is presented.

PMID- 19101566
TI  - Crystal structure of a major outer membrane protein from Thermus thermophilus
      HB27.
AB  - The thermophilic eubacterium Thermus thermophilus belongs to one of the oldest
      branches of evolution and has a multilayered cell envelope that differs from that
      of modern Gram-negative bacteria. Its outer membrane contains integral outer
      membrane proteins (OMPs), of which only a few are characterized. TtoA, a new beta
      barrel OMP, was identified by searching the genome sequence of strain HB27 for
      the presence of a C-terminal signature sequence. The structure of TtoA was
      determined to a resolution of 2.8 A, representing the first crystal structure of
      an OMP from a thermophilic bacterium. TtoA consists of an eight-stranded beta
      barrel with a large extracellular part to which a divalent cation is bound. A
      five-stranded extracellular beta-sheet protrudes out of the membrane-embedded
      transmembrane barrel and is stabilized by a disulfide bridge. The edge of this
      beta-sheet forms crystal contacts that could mimic interactions with other
      proteins. In modern Gram-negative bacteria, the C-terminal signature sequence of
      OMPs is required for binding to an Omp85 family protein as a prerequisite for its
      assembly. We present hints that a similar assembly pathway exists in T.
      thermophilus by an in vitro binding assay, where unfolded TtoA binds to the
      Thermus Omp85 family protein TtOmp85, while a mutant without the signature
      sequence does not.

PMID- 19101565
TI  - How to switch off a histidine kinase: crystal structure of Geobacillus
      stearothermophilus KinB with the inhibitor Sda.
AB  - Entry to sporulation in bacilli is governed by a histidine kinase phosphorelay, a
      variation of the predominant signal transduction mechanism in prokaryotes. Sda
      directly inhibits sporulation histidine kinases in response to DNA damage and
      replication defects. We determined a 2.0-A-resolution X-ray crystal structure of
      the intact cytoplasmic catalytic core [comprising the dimerization and histidine
      phosphotransfer domain (DHp domain), connected to the ATP binding catalytic
      domain] of the Geobacillus stearothermophilus sporulation kinase KinB complexed
      with Sda. Structural and biochemical analyses reveal that Sda binds to the base
      of the DHp domain and prevents molecular transactions with the DHp domain to
      which it is bound by acting as a simple molecular barricade. Sda acts to
      sterically block communication between the catalytic domain and the DHp domain,
      which is required for autophosphorylation, as well as to sterically block
      communication between the response regulator Spo0F and the DHp domain, which is
      required for phosphotransfer and phosphatase activities.

PMID- 19101567
TI  - Distinct activities of Escherichia coli small heat shock proteins IbpA and IbpB
      promote efficient protein disaggregation.
AB  - It has been proposed that small heat shock proteins (sHsps) associate with
      aggregated proteins and change their physical properties in such a way that
      chaperone-mediated disaggregation and refolding become much more efficient. Here,
      we investigate the influence of two Escherichia coli sHsps, IbpA and IbpB, on the
      properties of aggregates formed under heat shock conditions and the
      susceptibility of these aggregates to chaperone-dependent reactivation. Our
      results show that the presence of IbpA during heat denaturation is sufficient to
      change the macroscopic properties of aggregates. The aggregates are substantially
      smaller than aggregates formed in the absence of sHsps and they are stained
      differently on electron micrographs. Moreover, these aggregates are
      indistinguishable, by electron microscopy studies and sedimentation analysis,
      from aggregates obtained during heat denaturation in the presence of IbpA and
      IbpB. However, the morphological similarity between these two types of aggregates
      does not correlate with similar susceptibility to Hsp100-Hsp70-dependent
      reactivation. The presence of IbpA alone during substrate denaturation does not
      increase the efficiency of the subsequent Hsp100-Hsp70-dependent reactivation. On
      the contrary, substantial inhibition of this process is observed. IbpB associates
      with aggregates at high temperature due to its interaction with IbpA and releases
      the IbpA-mediated inhibitory effect. Our results suggest there is an interplay
      between IbpA and IbpB in promoting Hsp100-Hsp70-mediated disaggregation of
      protein aggregates. Although each seems to play a different role in this process,
      they cooperate to stabilize protein aggregates in a disaggregation-competent
      state.

PMID- 19101568
TI  - Stability analysis of gliding flight of a swallowtail butterfly Papilio xuthus.
AB  - Preliminary observation of the flights of swallowtail butterfly Papilio xuthus
      revealed that its dihedral angle is larger than 30 degrees and that the section
      of its left hind wing close to its body and the counterpart of its right hind
      wing actually clap and form a "vertical tail". In this study, the effects of
      these two features on the lateral-directional dynamic flight stability of these
      butterflies were analyzed theoretically and revealed the following: (a) when the
      dihedral angle is larger than 30 degrees , the lateral-directional motion of the
      swallowtail becomes stable; (b) the vertical tail stabilizes the dutch roll mode;
      (c) the effects of the dihedral angle on the roll and spiral modes of a
      swallowtail are qualitatively the same as those of a meter-sized airplane; and
      (d) with increasing dihedral angle, the stability of the dutch roll mode
      decreases for a meter-sized airplane with vertical and horizontal tails but
      increases for the swallowtail. A possible explanation for the latter effect is
      the smaller Reynolds number of the insect that causes the drag coefficient of the
      swallowtail wings to increase more rapidly with an increasing angle of attack
      compared to a large airplane.

PMID- 19101569
TI  - Evolutionary branching of virulence in a single-infection model.
AB  - This study explores the evolutionary dynamics of pathogen virulence in a single
      infection model with density-dependent mortality. Although virulence is not an
      adaptation of the pathogen per se, it is generally believed to be an inevitable
      by-product of a pathogen's need to propagate and transmit to new hosts: an
      increase in virulence will parallel an increase in transmission efficacy. The
      exact characteristics of the trade-off curve defined by this relationship are
      important with respect to possible evolutionary scenarios. We conduct a critical
      function analysis, a method that exposes the evolutionary outcome resulting from
      trade-offs of arbitrary shape, and find that this simple model can display a wide
      variety of evolutionary dynamics; comprising multiple stable attractors,
      evolutionary repellors, and most notably, evolutionary branching points. We
      identify the conditions under which the different evolutionary outcomes are
      realised. Our analysis furthermore considers the evolution of coexisting strains,
      and identifies the trade-off characteristics that will support an evolutionarily
      stable dimorphic state. We find that an evolutionarily stable dimorphism may
      exist also in the absence of a branching point in the monomorphic state. The
      analysis reveals that an evolutionarily stable dimorphism will always be
      attracting and that no further branching is possible under this model. We discuss
      our results in relation to the dimension of the environmental feedback inherent
      in the model, and to results from previous studies and models of evolution of
      virulence.

PMID- 19101570
TI  - Protective effect of caffeic acid against beta-amyloid-induced neurotoxicity by
      the inhibition of calcium influx and tau phosphorylation.
AB  - AIMS: The progressive accumulation of beta-amyloid peptide (Abeta), in the form
      of senile plaques, has been recognized as one of the major causes of Alzheimer's
      disease (AD) pathology. Increased production of Abeta and the aggregation of
      Abeta to oligomers have been reported to trigger neurotoxicity, oxidative damage
      and inflammation. Furthermore, Abeta-induced tau hyperphosphorylation and
      neurotoxicity are downstream of Abeta. Therefore, we studied the possible
      neuroprotective effects of caffeic acid against Abeta-induced toxicity. MAIN
      METHODS: Treatment of PC12 cells with 10 microM Abeta (25-35) for 24 h
      significantly decreased the cell viability; this was accompanied by an increase
      in intracellular calcium levels and tau phosphorylation with GSK-3beta (glycogen
      synthase kinase-3beta) activation (phosphorylation). KEY FINDINGS: However,
      pretreatment of the PC12 cells with 10 and 20 microg/ml of caffeic acid, for 1 h
      prior to Abeta, significantly reversed the Abeta-induced neurotoxicity by
      attenuating the elevation of intracellular calcium levels and tau
      phosphorylation. SIGNIFICANCE: Taken together, these results suggest that caffeic
      acid protected the PC12 cells against Abeta-induced toxicity. In addition, the
      neuroprotective mechanisms of caffeic acid against Abeta attenuated intracellular
      calcium influx and decreased tau phosphorylation by the reduction of GSK-3beta
      activation.

PMID- 19101571
TI  - Minocycline prevents Abeta(25-35)-induced reduction of somatostatin and
      neprilysin content in rat temporal cortex.
AB  - AIMS: Tetracyclines have been demonstrated to inhibit formation of beta-amyloid
      (Abeta) aggregates and to disassemble preformed fibrils. Minocycline, a semi
      synthetic second-generation tetracycline, can reverse Abeta-induced impairment of
      cognitive functions. Since somatostatin is involved in cognition and we recently
      showed that Abeta(25-35) lowers somatostatin expression in the rat temporal
      cortex, our aim here was to analyze the effects of minocycline on somatostatin
      immunoreactivity and mRNA levels in the temporal cortex of Abeta(25-35)-infused
      and healthy rats. Moreover, since brain levels of neprilysin, an Abeta-degrading
      enzyme, decrease with age, favoring the appearance of senile neuritic plaques, we
      tested whether minocyline could affect neprilysin expression. MAIN METHODS:
      Wistar rats were thus injected with minocycline twice on the first day of
      treatment. On the following day, and during 14 days, Abeta(25-35) or vehicle were
      administered. Minocycline was injected once again on days 13 and 14. All animals
      were sacrificed 24 h after the last drug injection. KEY FINDINGS: Minocycline
      abrogated the Abeta(25-35)-induced decrease of somatostatin-like immunoreactive
      content, somatostatin mRNA levels, phosphorylated-CREB content and neprilysin
      levels. Minocycline alone enhanced these targets. SIGNIFICANCE: Our findings
      indicate that minocycline prevents the deleterious effects of Abeta(25-35) on
      SRIF and neprilysin expression in the rat temporal cortex and that it has
      protective effects per se on these parameters.

PMID- 19101572
TI  - Association analysis between the Cdc6 G1321A polymorphism and the risk for non
      Hodgkin lymphoma and hepatocellular carcinoma.
AB  - Cdc6 play crucial roles in DNA replication and carcinogenesis. The biological
      significance of the Cdc6 G1321A polymorphism (V441I, rs13706) is still not
      elucidated. Here we examined the influence of this polymorphism on the function
      of Cdc6 and the individual's susceptibility to non-Hodgkin lymphoma (NHL) and
      hepatocellular carcinoma (HCC). Unconditional logistic regression analysis
      revealed that the risk for NHL was significantly reduced in both AG heterozygotes
      [odds ratio (OR)=0.67, P=0.019] and AA homozygotes (OR=0.54, P=0.026), compared
      with GG homozygotes. Further stratification by subtypes of NHL showed that the AG
      as well as combined AA/AG genotypes were associated with decreased risk for B
      cell-NHL (OR=0.62, P=0.011 and OR=0.61, P=0.006, respectively), especially for
      diffuse large B-cell lymphoma (DLBCL, OR=0.63, P=0.025 and OR=0.62, P=0.012,
      respectively). In addition, male individuals with the AA genotype displayed
      borderline significantly reduced risk for HCC (OR=0.48, P=0.054). Interestingly,
      the G1321A polymorphism did not affect caspase-mediated cleavage of Cdc6 during
      etoposide-induced apoptosis, but it was predicted to alter the secondary
      structure of Cdc6 mRNA. Our data provide the first evidence that the Cdc6 G1321A
      polymorphism is associated with decreased risk of cancer. Further studies are
      necessary to confirm the general validity of our findings.

PMID- 19101573
TI  - Damage to cellular and isolated DNA induced by a metabolite of aspirin.
AB  - Aspirin has been proposed as a possible chemopreventive agent. On the other hand,
      a recent cohort study showed that aspirin may increase the risk for pancreatic
      cancer. To clarify whether aspirin is potentially carcinogenic, we investigated
      the formation of 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodG), which is
      correlated with the incidence of cancer, in cultured cells treated with 2,3
      dihydroxybenzoic acid (2,3-DHBA), a metabolite of aspirin. 2,3-DHBA induced 8
      oxodG formation in the PANC-1 human pancreatic cancer cell line. 2,3-DHBA-induced
      DNA single-strand breaks were also revealed by comet assay using PANC-1 cells.
      Flow cytometric analyses showed that 2,3-DHBA increased the levels of
      intracellular reactive oxygen species (ROS) in PANC-1 cells. The 8-oxodG
      formation and ROS generation were also observed in the HL-60 leukemia cell line,
      but not in the hydrogen peroxide (H(2)O(2))-resistant clone HP100 cells,
      suggesting the involvement of H(2)O(2). In addition, an hprt mutation assay
      supported the mutagenicity of 2,3-DHBA. We investigated the mechanism underlying
      the 2,3-DHBA-induced DNA damage using (32)P-labeled DNA fragments of human tumor
      suppressor genes. 2,3-DHBA induced DNA damage in the presence of Cu(II) and NADH.
      DNA damage induced by 2,3-DHBA was enhanced by the addition of histone peptide-6
      [AKRHRK]. Interestingly, 2,3-DHBA and histone peptide-6 caused base damage in the
      5'-ACG-3' and 5'-CCG-3' sequences, hotspots of the p53 gene. Bathocuproine, a
      Cu(I) chelator, and catalase inhibited the DNA damage. Typical hydroxyl radical
      scavengers did not inhibit the DNA damage. These results suggest that ROS derived
      from the reaction of H(2)O(2) with Cu(I) participate in the DNA damage. In
      conclusion, 2,3-DHBA induces oxidative DNA damage and mutations, which may result
      in carcinogenesis.

PMID- 19101575
TI  - Inhibition of vinyl carbamate-induced lung tumors and Kras2 mutations by the
      garlic derivative diallyl sulfone.
AB  - Vinyl carbamate (VC) is derived from ethyl carbamate (EC), a chemical found in
      alcoholic beverages and fermented foods. The objectives of this study were to
      characterize the formation of lung tumors induced by VC in F1 (Big BluexA/J)
      mice, and to identify the mutations formed in the Kras2 gene. In addition, we
      have tested the hypothesis that pretreatment with diallyl sulfone (DASO2)
      inhibits the adverse effects of VC. Mice were treated with VC (60 mg/kg, i.p.) or
      DASO2 (50 mg/kg, p.o.) 2 h prior to VC (DASO2/VC). Lung tumor multiplicity was
      significantly lower (21%) in mice treated with DASO2/VC than with VC. Lung tumors
      induced by VC are manifested as solid or papillary tumors, with the latter being
      regarded as a more malignant phenotype as they demonstrate no growth
      restrictions. Solid (42%) and papillary tumors (58%) were found in similar
      proportions in VC-treated mice. The number of papillary tumors was significantly
      decreased (44.5%) in mice treated with DASO2/VC, while there was a proportional
      increase (44.5%) in the number of solid tumors. The number of tumors with
      mutations in the first and second exon of Kras2 was significantly lower after
      treatment with DASO2/VC (7%) than after treatment with VC (61%). The mutations
      were mainly found in codon 61, and were identified as A-->T transversions (31%)
      and A-->G transitions (25%) in the second base, and A-->T transversions (12%) in
      the third base. All of these mutations were significantly reduced by DASO2
      pretreatment. The number of tumors containing Kras2 mutations was highest (38%)
      in the large papillary tumors. Hence, mice treated with DASO2/VC had decreased
      frequencies of Kras2 mutations and reduced numbers of small and large papillary
      tumors, suggesting that activation of the Kras2 gene may be implicated in lung
      tumor formation and progression.

PMID- 19101574
TI  - The Fanconi anemia/BRCA gene network in zebrafish: embryonic expression and
      comparative genomics.
AB  - Fanconi anemia (FA) is a genetic disease resulting in bone marrow failure, high
      cancer risks, and infertility, and developmental anomalies including
      microphthalmia, microcephaly, hypoplastic radius and thumb. Here we present cDNA
      sequences, genetic mapping, and genomic analyses for the four previously
      undescribed zebrafish FA genes (fanci, fancj, fancm, and fancn), and show that
      they reverted to single copy after the teleost genome duplication. We tested the
      hypothesis that FA genes are expressed during embryonic development in tissues
      that are disrupted in human patients by investigating fanc gene expression
      patterns. We found fanc gene maternal message, which can provide Fanc proteins to
      repair DNA damage encountered in rapid cleavage divisions. Zygotic expression was
      broad but especially strong in eyes, central nervous system and hematopoietic
      tissues. In the pectoral fin bud at hatching, fanc genes were expressed
      specifically in the apical ectodermal ridge, a signaling center for fin/limb
      development that may be relevant to the radius/thumb anomaly of FA patients.
      Hatching embryos expressed fanc genes strongly in the oral epithelium, a site of
      squamous cell carcinomas in FA patients. Larval and adult zebrafish expressed
      fanc genes in proliferative regions of the brain, which may be related to
      microcephaly in FA. Mature ovaries and testes expressed fanc genes in specific
      stages of oocyte and spermatocyte development, which may be related to DNA repair
      during homologous recombination in meiosis and to infertility in human patients.
      The intestine strongly expressed some fanc genes specifically in proliferative
      zones. Our results show that zebrafish has a complete complement of fanc genes in
      single copy and that these genes are expressed in zebrafish embryos and adults in
      proliferative tissues that are often affected in FA patients. These results
      support the notion that zebrafish offers an attractive experimental system to
      help unravel mechanisms relevant not only to FA, but also to breast cancer, given
      the involvement of fancj (brip1), fancn (palb2) and fancd1 (brca2) in both
      conditions.

PMID- 19101577
TI  - N-acyldopamines control striatal input terminals via novel ligand-gated cation
      channels.
AB  - Endogenous analogues of capsaicin, N-acyldopamines, were previously identified
      from striatal extracts, but the putative presynaptic role of their receptor, the
      TRPV(1)R (formerly: vanilloid or capsaicin receptor) in the caudate-putamen is
      unclear. We found that the endogenous TRPV(1)R agonists, N-arachidonoyldopamine
      (NADA) and oleoyldopamine (OLDA) with EC(50) values in the nanomolar range, as
      well as the synthetic TRPV(1)R activator 2-aminoethoxydiphenylborane (2APB), and
      palmytoyldopamine (PALDA, another endogenous N-acyldopamine inactive at the
      TRPV(1)R), but not capsaicin or other endogenous and synthetic cannabinoids,
      triggered a rapid Ca(2+) entry with the concomitant stimulation of glutamate and
      dopamine release. These effects persisted in the TRPV(1)R null-mutant mice, and
      were insensitive to antagonists of common ionotropic receptors, to several
      TRPV(1)R antagonists and to the absence of K(+). Furthermore, these N
      acyldopamine receptors in glutamatergic and dopaminergic terminals are different
      based on their different sensitivity to anandamide, capsazepine and Gd(3+) at
      nanomolar concentrations. Altogether, novel ion channels instead of the TRPV(1)R
      mediate the presynaptic action of N-acyldopamines in the striatum of adult
      rodents.

PMID- 19101576
TI  - The Fanconi anemia protein interaction network: casting a wide net.
AB  - It has long been hypothesized that a defect in the repair of damaged DNA is
      central to the etiology of Fanconi anemia (FA). Indeed, an increased sensitivity
      of FA patient-derived cells to the lethal effects of various forms of DNA
      damaging agents was described over three decades ago [A.J. Fornace, Jr., J.B.
      Little, R.R. Weichselbaum, DNA repair in a Fanconi's anemia fibroblast cell
      strain, Biochim. Biophys. Acta 561 (1979) 99-109; Y. Fujiwara, M. Tatsumi, Repair
      of mitomycin C damage to DNA in mammalian cells and its impairment in Fanconi's
      anemia cells, Biochem. Biophys. Res. Commun. 66 (1975) 592-598; A.J. Rainbow, M.
      Howes, Defective repair of ultraviolet- and gamma-ray-damaged DNA in Fanconi's
      anaemia, Int. J. Radiat. Biol. Relat. Stud. Phys. Chem. Med. 31 (1977) 191-195].
      Furthermore, the cytological hallmark of FA, the DNA crosslink-induced radial
      chromosome formation, exemplifies an innate impairment in the repair of these
      particularly cytotoxic DNA lesions [A.D. Auerbach, Fanconi anemia diagnosis and
      the diepoxybutane (DEB) test, Exp. Hematol. 21 (1993) 731-733]. Precisely
      defining the collective role of the FA proteins in DNA repair, however, continues
      to be one of the most enigmatic and challenging questions in the FA field. The
      first six identified FA proteins (A, C, E, F, G, and D2) harbored no recognizable
      enzymatic features, precluding association with a specific metabolic process.
      Consequently, our knowledge of the role of the FA proteins in the DNA damage
      response has been gleaned primarily through biochemical association studies with
      non-FA proteins. Here, we provide a chronological discourse of the major FA
      protein interaction network discoveries, with particular emphasis on the DNA
      damage response, that have defined our current understanding of the molecular
      basis of FA.

PMID- 19101579
TI  - Breed differences in behavioural development in kittens.
AB  - Differences in behaviour of pure breed cats have been suggested but not wholly
      investigated. Oriental/Siamese/Abyssinian (OSA) kittens (n=43) were weekly
      compared with Norwegian Forest (NFO) kittens (n=39) from the 4th to the 10th week
      of age in a repeated Open Field Test (OFT) paradigm. Heart rate (HR) and rectal
      temperature (RT) before and after the test, and behavioural responses during the
      OFT were recorded. Behaviours registered were analysed by focal animal sampling.
      Significant breed differences were found; cats of the northern zones (NFO) seem
      to develop earlier thermoregulatory abilities. Precocious opening of eyes, higher
      locomotion scores and longer time spent standing, observed in OSA kittens may
      indicate an earlier neurological development. Inter breed differences recorded
      for exploration and locomotion seem to indicate coping style divergences: in the
      OFT challenging situation OSA kittens presented higher emotional tachycardia and
      performed more passively, with a faster decline in exploration and locomotion
      scores. NFO kittens exerted a more active behaviour as they spent more time
      exploring the arena and in escape attempts. Notwithstanding OSA and NFO cat
      selection was mainly aimed to improve divergent morphological traits, some
      different behavioural and physiological traits seem to have been maintained or co
      selected within each breed.

PMID- 19101580
TI  - The neuroprotective action of the mood stabilizing drugs lithium chloride and
      sodium valproate is mediated through the up-regulation of the homeodomain protein
      Six1.
AB  - The mood stabilizing agents lithium chloride (LiCl) and sodium valproate (VPA)
      have recently gained interest as potential neuroprotective therapeutics. However,
      exploitation of these therapeutic applications is hindered by both a lack of
      molecular understanding of the mode of action, and a number of sub-optimal
      properties, including a relatively small therapeutic window and variable patient
      response. Human neuroblastoma cells (SH-SY5Y) were exposed to 1 mM lithium
      chloride or 1 mM sodium valproate for 6 h or 72 h, and transcriptomes measured by
      Affymetrix U133A/B microarray. Statistically significant gene expression changes
      were identified using SAM software, with selected changes confirmed at transcript
      (TaqMan) and protein (Western blotting) levels. Finally, anti-apoptotic action
      was measured by an in vitro fluorescent assay. Exposure of SH-SY5Y cells to
      therapeutically relevant concentrations of either lithium chloride or sodium
      valproate elicited 936 statistically significant changes in gene expression.
      Amongst these changes we observed a large (maximal 31.3-fold) increase in the
      expression of the homeodomain protein Six1, and have characterized the time- and
      dose-dependent up-regulation of this gene in response to both drugs. In addition,
      we demonstrate that, like LiCl or VPA treatment, Six1 over-expression protects SH
      SY5Y cells from staurosporine-induced apoptosis via the blockade of caspsase-3
      activation, whereas removal of Six1 protein via siRNA antagonises the ability of
      LiCl and VPA to protect SH-SY5Y cells from STS-induced apoptosis. These results
      provide a novel mechanistic rationale underlying the neuroprotective mechanism of
      LiCl and VPA, suggesting exciting possibilities for the development of novel
      therapeutic agents against neurodegenerative diseases such as Alzheimer's or
      Parkinsonism.

PMID- 19101578
TI  - No effect of different estrogen receptor ligands on cognition in adult female
      monkeys.
AB  - Many studies in women and animal models suggest that estrogens affect cognitive
      function. Yet, the mechanisms by which estrogens may impact cognition remain
      unclear. The goal of the present study was to assess the effects of different
      estrogen receptor (ER) ligands on cognitive function in adult ovariectomized
      female rhesus monkeys. The monkeys were tested for 6 weeks on a battery of memory
      and attentional tasks administered on a touchscreen: the object, face, and
      spatial versions of the Delayed Recognition Span Test (DRST) and a Visual Search
      task. Following a 2-week baseline period with oil vehicle treatment, monkeys were
      randomly assigned to one of 3 treatment groups: estradiol benzoate (EB),
      selective ERbeta agonist (diarylpropionitrile DPN) or selective ER modulator
      tamoxifen (TAM). In each treatment group, monkeys received oil vehicle for 2
      weeks and the drug for 2 weeks, in a cross-over design. After a 4-week washout, a
      subset of monkeys was re-tested on the battery when treated with a selective
      ERalpha agonist (propyl-pyrazole-triol, PPT) or oil vehicle. Overall, drug
      treatments had no or negligible effects on cognitive performance. These results
      support the contention that exogenous estrogens and selective estrogen receptor
      modulators (SERMS) do not significantly affect cognition in young adult female
      macaques. Additional studies are needed to determine whether the cognitive
      effects of estrogens in monkeys of more advanced age are mediated by ERbeta,
      ERalpha or complex interactions between the two receptors.

PMID- 19101581
TI  - Pig as an experimental model for the study of snake venom induced local tissue
      necrosis.
AB  - Local tissue necrosis due to snake envenoming has resulted in considerable
      chronic disability. Specific antivenom, though highly useful in systemic
      poisoning, is not very effective in preventing the local tissue damages which
      occur within minutes of envenomation. Most of the studies on local tissue
      necrosis have been done in rodents whose skin structures are significantly
      different from human skin structure. In this study, pig, which is similar to
      human in this respect, was used as an experimental model for the study of local
      tissue damage caused by snake venom. An intradermal (i.d.) injection of
      Calloselasma rhodostoma (CR) venom induced induration and hemorrhage at the same
      injection site, the areas of which could be estimated at 30-45 min and at 4h
      after injection, respectively. Both the hemorrhage and induration were dose
      dependent and a total of 24 data points of each assay per pig could be obtained.
      Catheterization of the jugular vein for gentle serial blood collection could be
      performed without any hematologic sequelae. Venom injected subcutaneously induced
      myonecrosis as demonstrated by the increment of serum creatine kinase (CK) level
      which peaked at 23 h. Furthermore, biopsies at varying distances and depths
      around the venom injection sites could be made within seconds of injection to
      study the pathological changes caused by snake venom. These results demonstrated
      that pig should be a useful animal model for the quantitation, pathogenesis and
      wound healing studies of snake venom induced local tissue necrosis, and for the
      search for effective treatment modality.

PMID- 19101582
TI  - Membrane-bound conformation of Naja nigricollis toxin gamma affects its membrane
      damaging activity.
AB  - To address whether the conformational events associated with the absorption of
      Naja nigricollis toxin gamma on water-lipid interface plays a vital role in its
      membrane-damaging activity, the present study is carried out. Membrane-damaging
      activity of toxin gamma on 1-palmitoyl-2-oleoyl-phosphatidylcholine (POPC)/1, 2
      dimyristoyl-phosphatidic acid (DMPA) vesicles was approximately 13-fold of that
      on 1, 2-dipalmitoyl-phosphatidylcholine (DPPC)/DMPA vesicles, while the binding
      affinity of toxin gamma for POPC/DMPA was twofold of that for DPPC/DMPA. Time
      resolved fluorescence, acrylamide quenching and Fourier transform infrared
      spectra showed that POPC/DMPA-bound toxin gamma and DPPC/DMPA-bound toxin gamma
      did not adopt the same conformation. Moreover, geometrical arrangement of toxin
      gamma in contact with POPC/DMPA vesicles was different from that with DPPC/DMPA
      vesicles as evidenced by N-(fluorescein-5-thiocarbamoyl)-1,2-dihexadecanoyl
      phosphatidylcholine fluorescence enhancement and cross-linking of membrane-bound
      toxin gamma. Taken together, our data show that different membrane packing
      densities arising from phospholipid acyl chain affect membrane-bound conformation
      of toxin gamma, thus changing its membrane-damaging activity.

PMID- 19101583
TI  - Antigenic, microbicidal and antiparasitic properties of an l-amino acid oxidase
      isolated from Bothrops jararaca snake venom.
AB  - Venoms from the bee Apis mellifera, the caterpillar Lonomia achelous, the spiders
      Lycosa sp. and Phoneutria nigriventer, the scorpions Tityus bahiensis and Tityus
      serrulatus, and the snakes Bothrops alternatus, Bothrops jararaca, Bothrops
      jararacussu, Bothrops moojeni, Bothrops neuwiedi, Crotalus durissus terrificus,
      and Lachesis muta were assayed (800mug/mL) for activity against Staphylococcus
      aureus. Venoms from B. jararaca and B. jararacussu showed the highest S. aureus
      growth inhibition and also against other Gram-positive and Gram-negative
      bacteria. To characterize the microbicidal component(s) produced by B. jararaca,
      venom was fractionated through gel exclusion chromatography. The high molecular
      weight, anti-S. aureus P1 fraction was further resolved by anion exchange
      chromatography through Mono Q columns using a 0-0.5M NaCl gradient. Bactericidal
      Mono Q fractions P5 and P6 showed significant LAAO activity using l-leucine as
      substrate. These fractions were pooled and subjected to Heparin affinity
      chromatography, which rendered a single LAAO activity peak. The anti-S. aureus
      activity was abolished by catalase, suggesting that the effect is dependent on
      H(2)O(2) production. SDS-PAGE of isolated LAAO indicated the presence of three
      isoforms since deglycosylation with a recombinant N-glycanase rendered a single
      38.2 kDa component. B. jararaca LAAO specific activity was 142.7 U/mg, based on
      the oxidation of l-leucine. The correlation between in vivo neutralization of
      lethal toxicity (ED(50)) and levels of horse therapeutic antibodies anti-LAAO
      measured by ELISA was investigated to predict the potency of Brazilian
      antibothropic antivenoms. Six horses were hyperimmunized with Bothrops venoms
      (50% from B. jararaca and 12.5% each from B. alternatus, B. jararacussu, B.
      neuwiedii and B. moojeni). To set up an indirect ELISA, B. jararaca LAAO and
      crude venom were used as antigens. Correlation coefficients (r) between ED(50)
      and ELISA antibody titers against B. jararaca venom and LAAO were 0.846 (p<0.001)
      and 0.747 (p<0.001), respectively. The hemolytic and leishmanicidal (anti
      Leishmania amazonensis) activity of LAAO was also determined.

PMID- 19101585
TI  - Anxiolytic-like effects of sanjoinine A isolated from Zizyphi Spinosi Semen:
      possible involvement of GABAergic transmission.
AB  - This experiment was performed to investigate the anxiolytic-like effects of
      sanjoinine A, one of the major alkaloid compounds in Zizyphi Spinosi Semen (ZSS),
      by using experimental paradigms of anxiety in comparison with a known anxiolytic,
      diazepam. Sanjoinine A (2.0 mg/kg) increased the percentage of time spent on the
      open arms and the number of open arms entries in the elevated plus-maze test,
      increased the number of head dips in the hole-board test, and increased the
      percentage of time spent in the center zone and the center zone locomotor
      distance in the open field box experiment. However, sanjoinine A (0.5, 1.0, 2.0
      mg/kg) had no effect on locomotor activity, while diazepam (2.0 mg/kg)
      significantly reduced locomotor activity. Sanjoinine A (0.5, 1.0, 2.0 mg/kg) did
      not influence the grip force in the grip strength meter test either. Molecular
      experiments showed that sanjoinine A (2.0, 5.0 microM) increased chloride influx
      in cultured cerebellar granule cells. In addition, sanjoinine A (5.0 microM)
      treatment resulted in over-expression of alpha- and gamma-subunits of GABA(A)
      receptors and glutamic acid decarboxylase (GAD65/67) in cultured cerebellar
      granule cells. It is concluded that sanjoinine A may have anxiolytic-like effects
      in the elevated plus-maze, hole-board test and open field test, and these effects
      may be mediated by GABAergic transmission.

PMID- 19101584
TI  - Fluoxetine does not alter the ability of dopamine D(1)- and D(2)-like agonists to
      substitute for cocaine in squirrel monkeys.
AB  - Fluoxetine has been shown to enhance several behavioral effects of cocaine,
      including its discriminative-stimulus effects. An interaction between increased
      serotonergic and dopaminergic actions produced by blockade of serotonin and
      dopamine reuptake, is one possible mechanism for the enhancement. The present
      study investigated the effects of fluoxetine on the cocaine-like discriminative
      stimulus effects of the D(2)-like agonists quinpirole and (-)-NPA, and the D(1)
      like agonist SKF 82958 in squirrel monkeys trained to discriminate cocaine. The
      direct dopaminergic agonists, injected 5 min before testing, produced maximal
      levels of cocaine-appropriate responding of 50% (0.3 mg/kg, SKF 82958), 67%
      (0.003 mg/kg, (-)-NPA), and 77% (0.1 mg/kg, quinpirole) with ED(50) values of
      0.43, 0.003, and 0.06 mg/kg, respectively. Fluoxetine at doses up to 10 mg/kg
      (also 5 min before testing) did not alter the effectiveness or the potency of any
      of the dopamine agonists in substituting for cocaine. The present failure of
      fluoxetine to alter the cocaine-like discriminative effects of the dopamine
      agonists is consistent with the notion that the mechanism underlying the
      enhancement of the effects of cocaine by fluoxetine is not simply an interaction
      between enhanced serotonergic and dopaminergic activation as it is not obtained
      with direct-acting dopamine receptor agonists.

PMID- 19101586
TI  - An acetylcholinesterase-independent mechanism for neurobehavioral impairments
      after chronic low level exposure to dichlorvos in rats.
AB  - The present study was designed to explore an alternate mechanism of action other
      than acetylcholinesterase inhibition for the chronic, low-level exposure to
      dichlorvos, an organophosphate, in vivo. Dichlorvos, at dose of 1.0 as well as
      6.0 mg/kg b. wt. for 12 weeks to rats showed impairment in neurobehavioral
      indices viz. rota rod, passive avoidance and water maze tests. Though higher dose
      of dichlorvos had a detrimental effect on acetylcholinesterase activity, no
      significant inhibition was seen with lower dose of dichlorvos for the same period
      of exposure i.e. 12 weeks. Muscarinic acetylcholine receptor binding studies
      revealed a decrease in the number of binding sites (B(max)) in low as well as
      high dose groups but the dissociation constant (K(d)) value was unaffected with
      both doses of dichlorvos. Use of selective ligands against M(1), M(2) and M(3)
      receptor subtypes indicated that M(2) is the major receptor subtype being
      affected by chronic low-level exposure to dichlorvos. Western blot analysis and
      immunofluorescence studies also confirmed these biochemical findings. Thus, the
      present study suggests that M(2) receptors may play a major role in the
      development of neurobehavioral impairments after chronic exposure to dichlorvos.

PMID- 19101587
TI  - Television news exposure is related to fear of breast cancer.
AB  - OBJECTIVE: This study assessed the relationship between exposure to breast cancer
      content in television news programs and fear of breast cancer. METHODS: A
      quantitative standardized Health and Media Interview Survey was administered to a
      random sample of 500 Flemish women aged 18-85 years in 2007. The survey contained
      closed measures on demographics, breast cancer fear, television exposure and
      potential confounding variables such as trait anxiety, perceived risk and
      experience with breast cancer. RESULTS: 80.6% of the women were moderately to
      very afraid of being diagnosed with breast cancer. Multinomial logistic
      regression results showed that women who had occasionally been exposed to breast
      cancer content in television news were 1.9 times more likely to be very afraid of
      breast cancer (95% CI 1.1-3.4). Women who had frequently been exposed were 3.3
      times more likely to be moderately afraid (95% CI 1.1-10), and 7.5 times more
      likely to be very afraid of breast cancer (95% CI 2.4-23.8). CONCLUSIONS: These
      results suggest a relationship between exposure to breast cancer coverage in
      television news programs and fear of breast cancer.

PMID- 19101588
TI  - Synthesized phosphorylated and aminated derivatives of fucoidan and their
      potential antioxidant activity in vitro.
AB  - Three sulfated polysaccharide derivatives (phosphorylated and aminated fucoidan)
      were synthesized, and their potential antioxidant activities were investigated
      employing various established in vitro systems. Two methods were used in
      phosphorylation fucoidan: polyphosphoric acid and POCl(3) method. Aminated
      fucoidan was prepared using the epichlorohydrin and ammonia water. All fucoidan
      derivatives possessed considerable antioxidant activity, and exhibited stronger
      antioxidant ability than fucoidan in certain tests. The phosphorylated fucoidan
      showed stronger hydroxyl radical and 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical
      scavenging activity and reducing power. The mechanism on influence the
      antioxidant activity of samples of phosphate and amino group was indicated.

PMID- 19101589
TI  - Biorecognition of Escherichia coli K88 adhesin for glycated porcine albumin.
AB  - Escherichia coli (E. coli) that expresses galactose-reactive lectins, like K88
      adhesin, causes high mortality among piglets. Carbohydrates that compete for
      adhesion could serve as an alternative for disease prevention. Porcine serum
      albumin (PSA) was modified by non-enzymatic glycation with lactose to produce PSA
      Lac or PSA-Glc beta (1-4) Gal, as confirmed by reduction of available free amino
      groups, increased molecular mass and by Ricinus communis lectin recognition. E.
      coli K88 binds to PSA-Lac treatments containing three and four lactoses,
      respectively. In addition, PSA-Lac partially inhibited K88 strain adherence to
      mucins. These results suggest that neoglycoconjugates obtained by non-enzymatic
      glycation of proteins may serve in the prophylaxis of piglets' diarrhea.

PMID- 19101590
TI  - Detection of phenoloxidase activity in early stages of the Pacific oyster
      Crassostrea gigas (Thunberg).
AB  - The presence of phenoloxidase (PO) activity was detected in different
      developmental stages of the Pacific oyster, Crassostrea gigas. A significant
      reduction in PO activity was observed from the 6h embryo stage to the day 11
      larvae by spectrophotometry. A progressive increase was also observed from the
      day 13 larvae right through to the juvenile stage. The microscopy studies with
      '6h embryo' and adult samples confirmed the presence of PO activity. Various
      modulators of PO activity were used to study the triggering of pro-phenoloxidase
      (proPO) activating system of C. gigas but also to confirm the exact nature of the
      monitored activity. The enzyme activation mechanisms appear to differ with the
      developmental stage: bacterial lipopolysaccharides constitute an early elicitor
      of the proPO-PO system, whereas a purified trypsin triggers proPO-PO system in C.
      gigas spat. Phenoloxidase activity was totally suppressed by PO-specific
      inhibitors such as beta-2-mercaptoethanol, sodium diethyldithiocarbonate and
      tropolone. This study demonstrated the selective response of PO-like activity by
      different elicitors and suggested that proPO-PO activating system, which is
      supposed to play an important function in non-self recognition and host immune
      reactions in oyster, is expressed early in the Pacific oyster, C. gigas.

PMID- 19101591
TI  - Removal of spatial biological artifacts in functional maps by local similarity
      minimization.
AB  - Functional maps obtained by various technologies, including optical imaging
      techniques, f-MRI, PET, and others, may be contaminated with biological artifacts
      such as vascular patterns or large patches of parenchyma. These artifacts
      originate mostly from changes in the microcirculation that result from either
      activity-dependent changes in volume or from oximetric changes that do not co
      localize with neuronal activity per se. Standard methods do not always suffice to
      reduce such artifacts, in which case conspicuous spatial artifacts mask details
      of the underlying activity patterns. Here we propose a simple algorithm that
      efficiently removes spatial biological artifacts contaminating high-resolution
      functional maps. We validated this procedure by applying it to cortical maps
      resulting from optical imaging, based either on voltage-sensitive dye signals or
      on intrinsic signals. To remove vascular spatial patterns we first constructed a
      template of typical artifacts (vascular/cardiac pulsation/vasomotion), using
      principle components derived from baseline information obtained in the absence of
      stimulation. Next, we modified this template by means of local similarity
      minimization (LSM), achieved by measuring neighborhood similarity between
      contaminated data and the artifact template and then abolishing the similarity.
      LSM thus removed spatial patterns originating from the cortical vasculature
      components, including large fields of capillary parenchyma, helping to unveil
      details of neuronal activity patterns that were otherwise masked by these
      vascular artifacts. Examples obtained from our imaging experiments with
      anaesthetized cats and behaving monkeys showed that the LSM method is both
      general and reproducible, and is often superior to other available procedures.

PMID- 19101592
TI  - Companies Claim to Fame and their scientific challenges in vaccine development.
AB  - Although basic scientific immunological knowledge is the foundation for the
      development of novel vaccination approaches, beyond proof of concept in animal
      models, translational scientific immunological efforts are obligatory for
      successful development of a vaccine for use in humans. Translational technology
      is developed/used by biotechnology companies to generate better, safer or cheaper
      vaccines. Their proprietary position and/or proprietary technology are the basis
      of services that they offer to other companies or for products that they develop
      themselves. Some of the translational challenges are described in this review. In
      addition, a number of novel technologies developed by several biotechnology
      companies in The Netherlands are described. This document however, is far from
      complete and highlights only a small part of it.

PMID- 19101593
TI  - Expression, purification, and characterization of recombinant NS-1, the porcine
      parvovirus non-structural protein.
AB  - The non-structural protein NS-1 of porcine parvovirus (PPV) could be a useful
      antigen for differentiating pigs infected with PPV from those vaccinated with
      inactivated whole virus. NS-1 was expressed in Escherichia coli using the pET-32a
      (+) vector. The fusion protein, which was expressed at a high level, was similar
      antigenically to the native NS-1 protein as determined by Western blot assay
      using polyclonal antibodies from pigs vaccinated with alive PPV vaccine. A simple
      procedure was used to purify the fusion protein. This research lays the
      foundation for using the NS-1 protein for clinical diagnosis of pigs infected
      with PPV vs. those vaccinated with inactivated whole virus vaccine.

PMID- 19101594
TI  - Urodilatin and dopamine: a new interaction in the kidney.
AB  - Since renal natriuretic peptide urodilatin (URO) exerts similar natriuretic and
      diuretic actions to those of atrial natriuretic factor (ANF), we hypothesized
      that URO regulates renal dopamine (DA) availability, contributing to Na(+), K(+)
      ATPase inhibition. URO (1-100 nM) increased (3)H-DA uptake in outer and
      juxtamedullar renal cortex and medulla slices from Sprague Dawley rats.
      Hydrocortisone blocked URO-stimulated DA uptake, demonstrating that DA uptake was
      extraneuronal. The natriuretic peptide receptor type A antagonist anantin blocked
      URO-dependent increase of (3)H-DA uptake, while the natriuretic peptide receptor
      type C agonist ANF 4-23-amide did not modify URO effect on DA uptake, suggesting
      that only natriuretic receptors type A are involved. Co-incubation of URO and ANF
      did not show additive effects on DA uptake. To test whether URO effect involves
      changes in Na(+), K(+)-ATPase activity we performed experiments in renal cortex
      samples of rats with DA synthesis and neuronal uptake inhibited by carbidopa and
      nomifensine, respectively. When endogenous DA synthesis was inhibited, URO or DA
      decreased Na(+), K(+)-ATPase activity. URO and DA added together, further
      decreased Na(+), K(+)-ATPase activity showing an additive effect on the sodium
      pump. Moreover, hydrocortisone reversed URO-DA over-inhibition of the enzyme,
      confirming that this inhibition is closely related to URO-stimulation on renal DA
      uptake. URO and DA could act via a common intracellular pathway to decrease
      sodium and water tubular reabsorption, contributing to its natriuretic and
      diuretic effects.

PMID- 19101595
TI  - Short-chain fatty acid signaling pathways in bovine mammary epithelial cells.
AB  - GPR41 and 43 have recently been identified as G-protein-coupled cell-surface
      receptors for short-chain fatty acids (SCFAs). Bovine orthologs of GPR41 and 43
      (bGPR41 and 43) mRNA were detected by RT-PCR in cloned bovine mammary epithelial
      cells (bMEC) and various lactation stages of bovine mammary gland. Acetate and
      propionate caused an increase in intracellular Ca(2+) concentrations in these
      cells that was blocked by the treatment with pertussis toxin (PTX). SCFAs
      significantly reduced forskolin-induced cAMP concentrations in these cells. The
      phosphorylation of mitogen-activated protein kinase (MAPK) p38 was selectively
      increased by SCFAs. The downstream substrate heat shock protein 27 (HSP27) was
      also phosphorylated by SCFAs at Ser-78 and -82, but not -15. These results
      suggest that bGPR41 mainly, but not bGPR43, mediate SCFA signaling in mammary
      epithelial cells and thereby plays some important role in mammary gland.

PMID- 19101596
TI  - Characterization of the insulinostatic effect of urotensin II: a study in the
      perfused rat pancreas.
AB  - We have investigated the effect of urotensin II (UII) on insulin secretion at
      normal and high glucose concentrations as well as induced by secretagogues acting
      on the B cell via different mechanisms. The study was performed in the perfused
      rat pancreas. UII, at 1 nM, blocked the insulin response to an increase in
      perfusate glucose concentration from 5.5 to 9 mM while failed to significantly
      modify insulin secretion at higher glucose levels (from 9 to 13 mM). The
      insulinotropic effect of this glucose challenge was reduced by 10 nM UII. UII, at
      1 nM, inhibited tolbutamide-induced insulin secretion, whereas, it did not affect
      KCl-induced insulin release. UII inhibited exendin-4-induced insulin secretion,
      an effect not observed in pertussis toxin-treated rats. CONCLUSION: 1) B cells
      are less sensitive to UII at a high glucose level than at a low glucose. 2) The
      inhibitory effect of UII on both glucose and tolbutamide-induced insulin release,
      suggests the implication of ATP-dependent K(+) channels. The insulinostatic
      effect of UII was not observed during KCl stimulation, a condition in which these
      channels are overridden. 3) The insulinostatic effect of UII can also be mediated
      by its inhibitory action on the adenylate cyclase/cAMP system via a pertussis
      toxin-sensitive G(i) protein.

PMID- 19101597
TI  - RXFP1-inactive relaxin activates human glucocorticoid receptor: further
      investigations into the relaxin-GR pathway.
AB  - The relaxin peptide family regulates diverse biological functions (central
      nervous processes, reproduction, cardiovascular and kidney function, and
      connective tissue composition) through different G protein-coupled receptors. We
      reported earlier that human relaxin-2 and porcine relaxin additionally interact
      with the human glucocorticoid receptor (GR) in an agonistic manner. Here we
      investigated whether the membrane receptor RXFP1 is critically involved in this
      pathway. We used chemically modified porcine relaxin which was biologically
      inactive at RXFP1. Native porcine relaxin, but not the modified peptide affected
      RXFP1-dependent and GR-independent readouts: ERK-1/2 and Akt phosphorylation as
      well as up-regulation of Akt and endothelin type-B receptor. In contrast, relaxin
      and modified relaxin inhibited endotoxin-stimulated secretion of TNF-alpha and IL
      6 by human macrophages, an effect sensitive to the glucocorticoid receptor
      antagonists RU-486 and D-06. Both relaxins caused Ser(211) phosphorylation of GR,
      a biomarker of agonist-related receptor activation. Relaxin-induced accumulation
      of Ser(211)-phosphorylated GR was found in the cytoplasm and nucleus of HeLa
      cells, in endothelial cells, and in transfected HT-29 cells. In AP-1-luciferase
      assays, relaxin and modified relaxin inhibited endotoxin-induced activation of AP
      1, a transcription factor essentially involved in endotoxin signaling. This study
      suggests that the inability of relaxin to interact with its membrane receptor
      does not interfere with its ability to activate GR.

PMID- 19101598
TI  - Exploratory randomised controlled trial of a mindfulness-based weight loss
      intervention for women.
AB  - To explore the efficacy of a mindfulness-based weight loss intervention for
      women. Sixty-two women (ages 19-64; BMI 22.5-52.1) who were attempting to lose
      weight were randomised to an intervention or control condition. The former were
      invited to attend four 2-h workshops, the latter were asked to continue with
      their normal diets. Data were collected at baseline, 4 and 6 months. BMI,
      physical activity, mental health. At 6 months intervention participants showed
      significantly greater increases in physical activity compared to controls (p<.05)
      but no significant differences in weight loss or mental health. However, when
      intervention participants who reported 'never' applying the workshop principles
      at 6 months (n=7) were excluded, results showed both significantly greater
      increases in physical activity (3.1 sessions per week relative to controls,
      p<.05) and significantly greater reductions in BMI (0.96 relative to controls,
      equivalent to 2.32 kg, p<0.5). Reductions in BMI were mediated primarily by
      reductions in binge eating. Despite its brevity, the intervention was successful
      at bringing about change. Further refinements should increase its efficacy.

PMID- 19101599
TI  - Effects of complete whey-protein breakfasts versus whey without GMP-breakfasts on
      energy intake and satiety.
AB  - AIM: To compare the effects of whey versus whey without glycomacropeptide (GMP)
      in a high and a normal amount of protein in a breakfast custard on satiety and
      energy intake (EI), taking concentrations of amino acids (AA), glucose, insulin,
      glucagon-like peptide 1 (GLP-1) and ghrelin into account. METHODS: Twenty-five
      healthy subjects (mean+/-S.E.M., BMI: 23.9+/-0.3 kg/m(2); age: 22+/-1 years)
      received a breakfast containing whey or whey without GMP as protein type with
      10/55/35 or 25/55/20 En% protein/carbohydrate/fat in a randomized, single-blind
      design. Appetite profile (Visual Analogue Scale, VAS), glucose, insulin, GLP-1,
      ghrelin and AA concentrations were measured, and the adequate moment for ad
      libitum lunch was determined based on differences in ghrelin concentration. In a
      second set of experiments subjects received the same breakfasts; ad libitum lunch
      was offered at the pre-determined moment. RESULTS: After a breakfast with 25 En%
      protein increases in insulin and GLP-1 and decreases in ghrelin concentrations
      were larger; increases in satiety ratings were lower than after 10 En% (p<0.05);
      there was a treatment x time interaction effect on glucose and insulin
      concentrations (p<0.001). After a breakfast with whey without GMP insulin
      concentrations were increased more than after whey (p<0.05). EI at lunch was
      lower after whey than after whey without GMP (2877+/-165 kJ versus 3208+/-178 kJ,
      p<0.05), coinciding with more increased concentrations of serine, threonine,
      alanine, alpha-aminobutyric acid and isoleucine (p<0.05). CONCLUSION: GMP as a
      whey-fraction reduced energy intake coinciding with increased concentrations of
      certain amino acids, irrespective of the concentration of whey-protein. Although
      between different concentrations of whey-protein differences in hormone responses
      were observed, these were unrelated to satiety ratings or energy intake.

PMID- 19101600
TI  - A discrete computer model of the immune system reveals competitive interactions
      between the humoral and cellular branch and between cross-reacting memory and
      naive responses.
AB  - In an agent-based computer model, we simulate the formation and recall of anti
      virus immunological memory. Specifically we try to predict what will happen, both
      to the response and to memory, when the second infecting virus is partly
      different from the first one, and when the cross-reactivity of the two branches
      of the immune system (IS), humoral and cellular, is asymmetrical, or "split". The
      simulations explore systematically epitope distances, and measure all changes in
      affinity, cellularity and efficiency in clearing the infection. Besides obvious
      cooperation, they reveal powerful competitions between the branches, and more
      intriguing, between cross-reacting and new responses when the latter suffer the
      competition by preformed cell-rich but inefficient clones, as memory, usually an
      asset, becomes a liability.

PMID- 19101601
TI  - Alteration of xenobiotic metabolizing enzymes by resveratrol in liver and lung of
      CD1 mice.
AB  - Conflicting data on the anticancer properties of the polyphenolic natural product
      resveratrol (RSV) have been reported. Since the inhibition of "bioactivating"
      Phase-I xenobiotic metabolizing enzymes (XMEs) and/or induction of "detoxifying"
      Phase-II XMEs have long been considered important cancer chemopreventive
      strategies, in the current study we investigated the effect of RSV treatment on
      several Cytochrome P450 (CYP)-dependent oxidations and Phase-II markers in liver
      and lung subcellular preparations from CD1 male mice. These mice were i.p treated
      with RSV (25 or 50mg/Kg b.w.) daily for one or for seven consecutive days. Using
      either specific probes for different CYPs, or the regio- and stereo-selective
      metabolism of testosterone, we found that most of the Phase-I XMEs were
      significantly suppressed (up to approximately 61% loss for the CYP3A1/2-linked 6
      beta-hydroxylation of testosterone in liver and up to approximately 97% loss for
      2 alpha-hydroxylase in lung) following RSV treatment for 7 days at 50mg/kg b.w.
      Glutathione S-transferase was significantly inhibited, particularly in lung
      (approximately 76% loss of activity) after single administration of 25mg/kg b.w.
      A different response for the UDP-glucuronosyl transferase was observed, where a
      significant induction was seen (approximately 83%) in the liver and a significant
      reduction was observed in the lung (up to approximately 83% loss) following
      treatment with 25mg/kg b.w. for seven days. These data indicate that murine XMEs
      are altered by RSV, and that this alteration is dependent on the RSV dose,
      duration and way of administration. These results could provide mechanistic
      explanations for the conflicting chemopreventive results reported for RSV.

PMID- 19101602
TI  - Approaches to risk assessment in food allergy: report from a workshop
      ''developing a framework for assessing the risk from allergenic foods".
AB  - A workshop was organised to investigate whether risk assessment strategies and
      methodologies used in classical/conventional toxicology may be used for risk
      assessment of allergenic foods, to discuss the advantages and limitations of
      different approaches and to determine the research needed to move the area
      forward. Three possible approaches to safety assessment and risk assessment for
      allergenic foods were presented and discussed: safety assessment using
      NOAEL/LOAEL and uncertainty factors, safety assessment using Benchmark Dose and
      Margin of Exposure (MoE), and risk assessment using probabilistic models. The
      workshop concluded that all the three approaches to safety and risk assessment of
      allergenic foods should continue to be considered. A particular strength of the
      MoE and probabilistic approaches is that they do not rely on low-dose
      extrapolations with its inherent issues. Probabilistic modelling is considered to
      be the most promising approach for use in population risk assessment (which is a
      particular focus for risk managers). For all approaches, further improvement of
      input data is desirable, particularly data on consumption patterns/food choices
      in food allergic consumers, data on minimum eliciting doses and data that can be
      used to evaluate whether the whole population at risk has been modelled
      accurately. Specific research topics were identified.

PMID- 19101603
TI  - Protective effect of the extracts from Cnidium officinale against oxidative
      damage induced by hydrogen peroxide via antioxidant effect.
AB  - The dried rhizomes of Cnidium officinale are used as herbal drugs in the
      treatment of pain, inflammation, menstrual disturbance and antivitamin deficiency
      disease, and also act as a blood pressure depressant. In addition, there are
      several reports suggesting that they have pharmacological properties to tumor
      metastasis and angiogenesis, and that they act as an inhibitor of high glucose
      induced proliferation of glomerular mesangial cells. However, little has been
      known about the functional role of the extracts from C. officinale on oxidative
      DNA damage and apoptosis caused by ROS. In this work, we have investigated the
      DPPH radical, hydroxyl radical and intracellular ROS scavenging capacity, and
      Fe(2+) chelating activity of the extracts from C. officinale. In addition, we
      evaluated whether the extracts are capable of reducing H(2)O(2)-induced DNA and
      cell damage in the human skin fibroblast cell. These extracts showed a dose
      dependent free-radical scavenging capacity and a protective effect on DNA damage
      and the lipid peroxidation causing the cell damage by ROS. These antioxidant
      activities and inhibitory effects of the extracts on DNA and cell damage may
      further explain that C. officinale is useful as a herbal medicine for cancer
      chemoprevention.

PMID- 19101604
TI  - Pterostilbene from Vitis coignetiae protect H2O2-induced inhibition of gap
      junctional intercellular communication in rat liver cell line.
AB  - In this study, we identified various stilbenoids derived from Vitis coignetiae
      and investigated the protective effect of the main component, pterostilbene,
      against the inhibition of gap junctional intercellular communication (GJIC)
      induced by H(2)O(2) in WB-F344 rat liver epithelial cells. We analyzed seven
      kinds of stilbenoids, pterostilbene, astringin, piceid, vitisin, rhaponticin,
      resveratrol, and rhapontigenin, using DAD/UV HPLC. Total stilbenoid content was
      127.37+/-19.29 mg/100g dry weight. Pretreatment with 0.5, 1.0, and 5.0 microM
      pterostilbene for 24h was shown to recover GJIC blocked by 500 microM H(2)O(2).
      Pretreatment with pterostilbene prevented the inhibition of GJIC via the down
      regulation of connexin43 phosphorylation by the inactivation of ERK1/2 and p38
      MAP kinase. Our results suggest that pterostilbene may be a functional
      chemopreventative agent and that dietary exposure of pterostilbene would be
      helpful for improving health.

PMID- 19101605
TI  - Vasoactive intestinal peptide (VIP) induces transactivation of EGFR and HER2 in
      human breast cancer cells.
AB  - We analyzed the cross-talk between receptors for vasoactive intestinal peptide
      (VIP) and the human epidermal growth factor family of tyrosine kinase receptors
      (HER) in oestrogen-dependent (T47D) and oestrogen-independent (MDA-MB-468) human
      breast cancer cells. VIP treatment slowly increased the expression levels of EGFR
      but it rapidly augmented phosphorylation of EGFR and HER2 in both cell lines.
      This pattern of HERs transactivation was blocked by the specific VIP antagonist
      JV-1-53, supporting the direct involvement of VIP receptors in formation of P
      EGFR and P-HER2. VIP-induced transactivation was also abolished by H89 (protein
      kinase A inhibitor), PP2 (Src inhibitor) or TAPI-1 (inhibitor of matrix
      metalloproteases), following a differential pattern. These results shed a new
      light on the specific signalling pathways involved in EGFR/HER2 transactivation
      by VPAC receptors and suggest the potential usefulness of VIP receptor
      antagonists together with current antibodies against EGFR/HER2 and/or tyrosine
      kinase inhibitors for breast cancer therapy.

PMID- 19101606
TI  - Studying how flies make sperm--investigating gene function in Drosophila testes.
AB  - The majority of the audience at the European Testis Workshop were actively
      researching mammalian spermatogenesis or sperm function. In this paper therefore
      I follow the brief I had for my contribution to the meeting in the session "non
      mammalian models of spermatogenesis", which was to explain practical approaches
      to research in Drosophila spermatogenesis, illuminating how what we learn in
      model organisms can be relevant to male fertility research in mammals. I discuss
      techniques and resources available to fly spermatogenesis researchers, and
      indicate how I have applied them in my lab to understand regulation of gene
      expression in spermatogenesis.

PMID- 19101607
TI  - Conference on the Adrenal Cortex 2008, Burlingame, CA June 11-14, 2008.

PMID- 19101608
TI  - Prenatal diagnosis and treatment of congenital adrenal hyperplasia due to 21
      hydroxylase deficiency.
AB  - Congenital adrenal hyperplasia (CAH) applies to a group of inherited disorders
      caused by an enzyme deficiency in steroid biosynthesis. The most common form of
      CAH is 21-hydroxylase deficiency (21-OHD), which in its severe form can cause
      genital ambiguity in females. Affected females experience virilization both
      physically and psychologically. Steroid 21-OHD can be diagnosed in utero through
      molecular genetic analysis of fetal DNA. Appropriate prenatal treatment by
      dexamethasone administration to the at-risk pregnant mother is effective in
      reducing genital virilization in the fetus, thus avoiding unnecessary
      genitoplasty in affected females. Current data from large human studies show that
      prenatal diagnosis and treatment are safe in the short term for both the fetus
      and the mother. Preliminary data from long-term studies support these results.

PMID- 19101609
TI  - Postnatal development of axosomatic synapses in the rat nucleus tractus
      solitarius: dorsal and ventral subnuclei differences.
AB  - Inhibitory axosomatic synapses could effectively suppress the excitability of
      postsynaptic cells. It is important to examine the development of inhibitory
      axosomatic synapses to understand the maturation of information processing. The
      caudal nucleus tractus solitarius (cNTS), which regulates the autonomic system,
      consists of several subnuclei. In the present study, development of axosomatic
      synapses in the dorsal and ventral subnuclei was examined by electron microscopy.
      In dorsal subnuclei, the percentage of GAD-positive terminals on the somata, the
      percentage of small cell somata with synapses and axosomatic synapse density
      drastically decreased from postnatal day (P) 5 to P10. In ventral subnuclei, the
      percentage of GAD-positive terminals on the soma, the percentage of small or
      large cell somata with synapses and axosomatic synapse density were maintained or
      increased from P5 to P10. Thus, decrease of inhibitory axosomatic synapses in
      dorsal subnuclei might facilitate maturation of fine receptive areas for
      peripheral inputs, while increase of inhibitory axosomatic synapses in ventral
      subnuclei might facilitate the establishment of an effective regulation system
      for cNTS output.

PMID- 19101610
TI  - Biochemical characterization of tau protein and its associated syndapin 1 and
      protein kinase Cepsilon for their functional regulation in rat brain.
AB  - BACKGROUND: We recently reported that both sulfatide and cholesterol-3-sulfate
      (SCS) function as potent stimulators for the GSK-3beta-mediated phosphorylation
      of tau protein (TP) in vitro [J. Biochem. 143 (2008) 359-367]. METHODS: By means
      of successive gel filtration on a Superdex 200 pg column and three distinct ion
      exchange column chromatographies, TP and its associated proteins were highly
      purified from the extract of rat brain. RESULTS: We found that (i) syndapin 1 and
      novel protein kinase Cepsilon (nPKCepsilon) were identified as the TP-associated
      proteins; (ii) SCS highly stimulated the phosphorylation of TP and syndapin 1 by
      nPKCepsilon as well as CK1; (iii) the full phosphorylation of TP and syndapin 1
      by nPKCepsilon in the presence of sulfatide resulted in their dissociation; (iv)
      TP primed by CK1 functioned as an effective phosphate acceptor for GSK-3beta; (v)
      syndapin 1 highly stimulated the GSK-3beta-mediated phosphorylation of TP; and
      (vi) TP isoforms were highly expressed in aged brain, whereas syndapin 1 was
      consistently detected in adult brain, but not in newborn brain. GENERAL
      SIGNIFICANCE: These results provided here suggest that (i) TP-associated
      nPKCepsilon suppresses the GSK-3beta-mediated phosphorylation of TP through the
      phosphorylation of GSK-3beta by the kinase in vitro; and (ii) SCS act as
      effective sole mediators to induce the GSK-3beta-mediated high phosphorylation of
      both TP and its associated syndapin 1 involved in the biochemical processes of
      neuronal diseases, including Alzheimer's disease.

PMID- 19101611
TI  - Conserved sequence in the aggrecan interglobular domain modulates cleavage by
      ADAMTS-4 and ADAMTS-5.
AB  - BACKGROUND: Cleavage of aggrecan by ADAMTS proteinases at specific sites within
      highly conserved regions may be important to normal physiological enzyme
      functions, as well as pathological degradation. METHODS: To examine ADAMTS
      selectivity, we assayed ADAMTS-4 and -5 cleavage of recombinant bovine aggrecan
      mutated at amino acids N-terminal or C-terminal to the interglobular domain
      cleavage site. RESULTS: Mutations of conserved amino acids from P18 to P12 to
      increase hydrophilicity resulted in ADAMTS-4 cleavage inhibition. Mutation of
      Thr, but not Asn within the conserved N-glycosylation motif Asn-Ile-Thr from P6
      to P4 enhanced cleavage. Mutation of conserved Thr residues from P22 to P17 to
      increase hydrophobicity enhanced ADAMTS-4 cleavage. A P4' Ser377Gln mutant
      inhibited cleavage by ADAMTS-4 and -5, while a neutral Ser377Ala mutant and
      species mimicking mutants Ser377Thr, Ser377Asn, and Arg375Leu were cleaved
      normally by ADAMTS-4. The Ser377Thr mutant, however, was resistant to cleavage by
      ADAMTS-5. CONCLUSION: We have identified multiple conserved amino acids within
      regions N- and C-terminal to the site of scission that may influence enzyme
      substrate recognition, and may interact with exosites on ADAMTS-4 and ADAMTS-5.
      GENERAL SIGNIFICANCE: Inhibition of the binding of ADAMTS-4 and ADAMTS-5 exosites
      to aggrecan should be explored as a therapeutic intervention for osteoarthritis.

PMID- 19101613
TI  - A comparison of two methods for assessing critical flicker fusion frequency in
      hens.
AB  - This paper compared two general methods for assessing critical fusion frequency
      in hens (gallus gallus domesticus). The first method was a conditional
      discrimination procedure with the stimuli presented successively. The second was
      a two-alternative forced-choice procedure with the stimuli presented
      simultaneously. It was found that both methods of stimulus presentation gave
      comparable results suggesting that either method is useful when investigating
      psychophysics in animals. The results also show that hens' critical fusion
      frequency is considerably higher than that of humans which may account for hens'
      inability to recognise images presented on standard computer or television
      monitors.

PMID- 19101614
TI  - Extensive analysis of EST sequences reveals that all cichlid species in Lake
      Victoria share almost identical transcript sets.
AB  - Lake Victoria harbors hundreds of cichlid species, which have aggressively
      developed their morphological features through their evolution. In particular,
      the shapes of jaws and teeth have diverged markedly, and correlate with feeding
      ecology. These species are believed to have explosively arisen within the last
      15,000 years and are therefore of particular interest to evolutionary biologists.
      Previously, we reported expressed sequence tags (ESTs) from two cichlid species,
      Haplochromis chilotes and H. sp. "redtailsheller", and provided a comparative EST
      analysis. In this study, we further examined the molecular basis for
      diversification of Lake Victoria cichlids by generating EST from another cichlid
      species, H. sp. "Matumbi hunter"; 9,219 clones were applied for sequence
      determination and 16,795 sequences were newly obtained from this EST set.
      Comparative analysis of the 68 genes common to the three cichlid species revealed
      that the degrees of genetic distance and the degrees of genetic polymorphism were
      highly similar for each pair-wise comparison, suggesting that the protein coding
      regions of the three cichlid genomes are essentially the same. Because the three
      species used for the comparative analysis were particularly diverged from each
      other in morphological and also ecological features, we concluded that the
      uniformity of transcript sequences among cichlid species in Lake Victoria is a
      global feature.

PMID- 19101612
TI  - Cyclic AMP-dependent protein kinase A and protein kinase C phosphorylate
      alpha4beta2 nicotinic receptor subunits at distinct stages of receptor formation
      and maturation.
AB  - Neuronal nicotinic receptor alpha4 subunits associated with nicotinic alpha4beta2
      receptors are phosphorylated by cyclic AMP-dependent protein kinase (PKA) and
      protein kinase C (PKC), but the stages of receptor formation during which
      phosphorylation occurs and the functional consequences of kinase activation are
      unknown. SH-EP1 cells transfected with DNAs coding for human alpha4 and/or beta2
      subunits were incubated with (32)Pi, and PKA or PKC was activated by forskolin or
      phorbol 12,13-dibutyrate, respectively. Immunoprecipitation and immunoblotting of
      proteins from cells expressing alpha4beta2 receptors or only alpha4 subunits were
      used to identify free alpha4 subunits, and alpha4 subunits present in immature
      alpha4beta2 complexes and mature alpha4beta2 pentamers containing complex
      carbohydrates. In the absence of kinase activation, phosphorylation of alpha4
      subunits associated with mature pentamers was three times higher than subunits
      associated with immature complexes. PKA and PKC activation increased
      phosphorylation of free alpha4 subunits on different serine residues; only PKC
      activation phosphorylated subunits associated with mature alpha4beta2 receptors.
      Activation of both PKA and PKC increased the density of membrane-associated
      receptors, but only PKC activation increased peak membrane currents. PKA and PKC
      activation also phosphorylated beta2 subunits associated with mature alpha4beta2
      receptors. Results indicate that activation of PKA and PKC leads to the
      phosphorylation alpha4beta2 receptors at different stages of receptor formation
      and maturation and has differential effects on the expression and function of
      human alpha4beta2 receptors.

PMID- 19101615
TI  - The molecular chaperone Hsp90 is a component of the cap-binding complex and
      interacts with the translational repressor Cup during Drosophila oogenesis.
AB  - In metazoa, the spatio-temporal translation of diverse mRNAs is essential to
      guarantee proper oocyte maturation and early embryogenesis. The eukaryotic
      translation initiation factor 4E (eIF4E), which binds the 5' cap structure of
      eukaryotic mRNAs, associates with either stimulatory or inhibitory factors to
      modulate protein synthesis. In order to identify novel factors that might act at
      the translational level during Drosophila oogenesis, we have undertaken a
      functional proteomic approach and isolated the product of the Hsp83 gene, the
      evolutionarily conserved chaperone Hsp90, as a specific component of the cap
      binding complex. Here we report that Hsp90 interacts in vitro with the
      translational repressor Cup. In addition, we show that Hsp83 and cup interact
      genetically, since lowering Hsp90 activity enhances the oogenesis alterations
      linked to diverse cup mutant alleles. Hsp90 and Cup co-localize in the cytoplasm
      of the developing germ-line cells within the germarium, thus suggesting a common
      function from the earliest stages of oogenesis. Taken together, our data start
      elucidating the role of Hsp90 during Drosophila female germ-line development and
      strengthen the idea that Cup has multiple essential functions during egg chamber
      development.

PMID- 19101616
TI  - Nanosized bicalutamide and its molecular structure in solvents.
AB  - Nanosized bicalutamide particles have been obtained by anti-solvent precipitation
      after screened DMSO and EtOH as co-solvents. The produced nanoparticles have been
      characterized by scanning electron microscopy (SEM), Fourier transform infrared
      spectrophotometry (FTIR), X-ray diffraction (XRD) and a dissolution test. The
      mean particle size of bicalutamide is about 450nm with a narrow distribution. The
      results of the dissolution test show that dissolution rate of the produced
      nanoparticles are higher than that of the raw material. Besides, DFT calculations
      of the bicalutamide conformers have firstly been presented. It is found that the
      calculated geometry structure of lower-energy conformer is very similar to the
      experimental structure existing within the crystal lattice. The solvent effects
      have been taken into account based on the polarizable continuum model (PCM). The
      computed results appear that the introduction of dielectric medium has obvious
      effect on the molecular geometry of bicalutamide.

PMID- 19101618
TI  - Cultural significance of medicinal plant families and species among Quechua
      farmers in Apillapampa, Bolivia.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: Medicinal plant use was investigated in
      Apillapampa, a community of subsistence farmers located in the semi-arid Bolivian
      Andes. AIM OF THE STUDY: The main objectives were to identify the culturally most
      significant medicinal plant families and species in Apillapampa. MATERIALS AND
      METHODS: A total of 341 medicinal plant species was inventoried during guided
      fieldtrips and transect sampling. Data on medicinal uses were obtained from
      fifteen local Quechua participants, eight of them being traditional healers.
      RESULTS: Contingency table and binomial analyses of medicinal plants used versus
      the total number of inventoried species per family showed that Solanaceae is
      significantly overused in traditional medicine, whereas Poaceae is underused.
      Also plants with a shrubby habitat are significantly overrepresented in the
      medicinal plant inventory, which most likely relates to their year-round
      availability to people as compared to most annual plants that disappear in the
      dry season. Our ranking of medicinal species according to cultural importance is
      based upon the Quality Use Agreement Value (QUAV) index we developed. This index
      takes into account (1) the average number of medicinal uses reported for each
      plant species by participants; (2) the perceived quality of those medicinal uses;
      and (3) participant consensus. CONCLUSIONS: According to the results, the QUAV
      index provides an easily derived and valid appraisal of a medicinal plant's
      cultural significance.

PMID- 19101617
TI  - In vitro elution of vancomycin/amikacin/steroid from solvent-free biodegradable
      scleral plugs.
AB  - The purpose of this report was to develop solvent-free biodegradable scleral
      plugs for vancomycin, amikacin and dexamethasone delivery for endophthalmitis
      treatment. To fabricate a biodegradable plug, polylactide-polyglycolide
      copolymers were pre-mixed with the drugs. The mixture was then compression molded
      and sintered to form a scleral plug of 1.4mm in diameter. An elution method was
      utilized to characterize the in vitro release characteristics of the antibiotics
      and the steroids over a 14-day period. The HPLC analysis and bacterial inhibition
      test showed that biodegradable scleral plugs released a high concentration
      resulting in significant activity of vancomycin and amikacin (well above the
      minimum inhibition concentrations) and dexamethasone in vitro, for the period of
      time needed to treat intraocular infection. A bacterial inhibition test was
      carried out to determine the relative activity of the released antibiotics. The
      activities of the eluted vancomycin and amikacin ranged from 69% to 89% and from
      66% to 88%, respectively. In addition, the experimental result suggests that one
      will be able to reduce the drug release rate and prolong the total release period
      of the plugs by adopting a lower antibiotic/steroid to polymer ratio, increasing
      the sintering temperature, or increasing the compression pressures.

PMID- 19101619
TI  - Bioactivity studies and chemical profile of the antidiabetic plant Genista
      tenera.
AB  - AIM OF THE STUDY: Genista tenera is a plant endemic to the island of Madeira and
      is used in folk medicine to control diabetes. In the present work we evaluate the
      antihyperglycaemic activity of its n-butanol extract and determine its
      chromatographic profile. In addition, this extract, the ethyl acetate and diethyl
      ether plant extracts were studied in order to assess the plant antioxidant and
      acetylcholinesterase inhibitory activities, as well as its cyto- and
      genotoxicities. MATERIALS AND METHODS: HPLC-DAD-ESI-MS was used to analyze the
      flavonoid profile of the n-butanol extract. The antihyperglycaemic activity of
      this extract was performed over streptozotocin induced diabetic Wistar rats (200
      mg/kg, bw/day), for 15 days. Antioxidant activity (DPPH assay) and
      acetylcholinesterase inhibitory effect (Ellman method) were also performed. Acute
      cytotoxicity and genotoxicity were assessed by proliferative index quantification
      and the short-term chromosomal aberration technique, after exposure of
      lymphocytes to the extracts. RESULTS AND CONCLUSIONS: The n-butanol extract,
      where 21 monoglycosyl and 12 diglycosyl flavonoids were detected, significantly
      lowered blood glucose levels, bringing them to normal values after 15 days of
      treatment. The best radical scavenging activity was observed for the ethyl
      acetate extract (48.7% at 139.1 microg/mL), which was also the most effective one
      at the minimal concentration tested. The highest acetylcholinesterase inhibitory
      activity (77.0% at 70.0 microg/mL) was also obtained with the ethyl acetate
      extract. In vitro toxicity studies showed no evidence for acute cytotoxicity or
      genotoxicity. This is the first report on antidiabetic activity of genus Genista.

PMID- 19101620
TI  - Immunomodulatory effects of Abnormal Savda Munsiq, a traditional Uighur medicine,
      on the combined stress mice.
AB  - OBJECTIVE: To investigate the immunomodulatory effects of ASMq, a herbal
      preparation used in Traditional Uighur Medicine, on the combined stress mice.
      MATERIALS AND METHODS: The combined stress was induced on mice by application of
      the electric-foot shock in a cold-dry environment and three different doses of
      ASMq were orally administered to the animals for 14 days. The effect of ASMq on
      the immune apparatus weight index, lymphocytes proliferation, serum levels of the
      cytokines, immunoglobulins, hemolysin and NK cells as well as the phagocytic
      activity of the macrophages were evaluated. RESULTS: Oral administration of ASMq
      was found to increase the thymus and spleen indices, lymphocytes proliferation
      induced by Con A and LPS, the percentage of CD4(+) in thymus, spleen and
      peripheral blood and restore the CD4(+)/CD8(+) ratio. The serum concentrations of
      INF-beta, IL-2, IL-6, IgG, NK cells and hemolysin were also increased. The
      macrophage phagocytic activity was also enhanced.

PMID- 19101621
TI  - Morus alba leaf extract stimulates 5'-AMP-activated protein kinase in isolated
      rat skeletal muscle.
AB  - AIM OF THE STUDY: Morus alba (mulberry) leaf is a natural therapeutic agent that
      has been shown to have an antidiabetic effect. We explored the possibility that
      5'-AMP-activated protein kinase (AMPK) is involved in metabolic enhancement by
      the Morus alba leaf. MATERIALS AND METHODS: Isolated rat epitrochlearis muscle
      was incubated in a buffer containing Morus alba leaf hot water extract (MLE) and
      the AMPK activation and related events were examined. RESULTS: In response to MLE
      treatment, the Thr(172) phosphorylation of the catalytic alpha subunit of AMPK,
      an essential step for full kinase activation increased in a dose- and time
      dependent manner. Ser(79) phosphorylation of acetyl CoA carboxylase, an
      intracellular substrate of AMPK, increased similarly. Analysis of isoform
      specific AMPK activity revealed that MLE activated both the alpha1 and alpha2
      isoforms of the catalytic subunit. This increase in enzyme activity was
      associated with an increased rate of 3-O-methyl-D-glucose transport in the
      absence of insulin and with phosphorylation of AS160, a signaling intermediary
      leading to glucose transporter 4 translocation. The intracellular energy status,
      estimated from the ATP and phosphocreatine concentrations, was not affected by
      MLE. CONCLUSION: MLE stimulates skeletal muscle AMPK activity acutely without
      changing the intracellular energy status.

PMID- 19101622
TI  - Ginsenoside Rg1, a major active component isolated from Panax notoginseng,
      restrains tubular epithelial to myofibroblast transition in vitro.
AB  - The medicinal herb, Panax notoginseng, has been used for thousands of years in
      traditional Chinese medicine and possesses anti-fibrosis properties. Epithelial
      myofibroblast transition (EMT) plays an important role in renal
      tubulointerstitial fibrosis. The present study was designed to examine whether
      ginsenoside Rg1, a major active component isolated from Panax notoginseng, has an
      ability to block this phenotypic transition in rat renal tubular epithelial cells
      (NRK-52E) induced by transforming growth factor-beta1 (TGF-beta1). The morphology
      of tubular epithelial-myofibroblast transition was observed through light
      microscope and transmission electron microscopy. alpha-SMA and E-cadherin are two
      markers of tubular epithelial-myofibroblast transition, their protein expressions
      were assessed by immunohistochemistry and western blot analysis. Gene expression
      of alpha-SMA as well as the two major extracellular matrix components collagen I
      and fibronectin was measured by real-time PCR analysis. Enzyme-linked
      immunosorbent assay was used to quantitatively detect collagen I and fibronectin
      in the supernatant. Our results revealed that ginsenoside Rg1 obviously blocked
      morphologic transformation in NRK-52E induced by TGF-beta1. Meanwhile,
      ginsenoside Rg1 inhibited the expression of alpha-SMA and the loss of E-cadherin,
      subsequently decreased the levels of collagen I and fibronectin in a dose
      dependent manner. In addition, western blot analysis indicated that ginsenoside
      Rg1 inhibited the expression of P-ERK1/2 in NRK-52E induced by TGF-beta1. These
      results suggest that ginsenoside Rg1 can restrain the process of EMT maybe via
      suppressing the expression of P-ERK1/2 in vitro.

PMID- 19101623
TI  - A 96-well flow cytometric screening assay for detecting in vitro phospholipidosis
      induction in the drug discovery phase.
AB  - Drug-induced phospholipidosis is caused by lysosomal accumulation of the drug,
      resulting in the disturbance of phospholipid degradation and a consequent
      excessive phospholipid accumulation. Depending on the type and number of tissues
      affected, phospholipidosis occurrence in test animals can raise safety issues,
      which may be critical for the risk assessment. Safety profiling of potential
      phospholipidosis-inducing drugs in the drug discovery phase can predict these
      late obstructions of drug development. For this purpose, a flow cytometric assay
      based on the difference in fluorescent phospholipid accumulation in a human
      monocyte cell line was initially established. Modifying the assay studying
      degradation of the fluorescent phospholipids instead of accumulation drastically
      improved sensitivity. By testing various phospholipidosis-inducers and negative
      compounds, it was found that the assay could detect the occurrence of
      phospholipidosis by a 2-fold difference in fluorescence compared to control
      cells, demonstrating the superior sensitivity of the novel approach.
      Implementation of a higher throughput 96-well flow cytometric set up did not
      affect the sensitivity of detection or the reproducibility of the assay. Based on
      an extended test set of reference compounds a profiling approach was introduced,
      by which we show we can rank our drug candidates according to their
      phospholipidosis-inducing potential.

PMID- 19101624
TI  - Metallic haptens induce differential phenotype of human dendritic cells through
      activation of mitogen-activated protein kinase and NF-kappaB pathways.
AB  - Dendritic cells (DCs) play a major role in the regulation of immune responses to
      a variety of antigens (Ag) and haptens which participate in the process of DC
      maturation. Indeed, metallic haptens are able to induce DC maturation in vitro
      but the mechanism of this maturation is not well understood. We and others have
      already shown that NiSO(4) activates p38 mitogen-activated protein kinases
      (p38MAPK), c-jun N-terminal kinase (JNK), extracellular signal-regulated kinase
      (ERK) and the transcription factor NF-kappaB during the early events of DCs
      maturation. However, the effect of other metallic haptens on DC maturation is
      still poorly understood. In the present study, using dendritic cells derived from
      CD34(+) cord blood cells, we showed that both NiSO(4) and CoCl(2) induced the
      expression of CD86, CD83, HLA-DR and CD40 and the production of IL-6 in human DCs
      while K(2)Cr(2)O(7) induced only a slight upregulation of CD86. Interestingly,
      only NiSO(4) was able to induce the production of IL-12p40. NiSO(4) and CoCl(2)
      but not K(2)Cr(2)O(7) were able to activate the MAPK pathway and the
      transcription factor NF-kappaB. The role of MAPKs in metals-induced DC maturation
      was then evaluated using well-described pharmacological inhibitors. Our results
      suggest that p38MAPK activation regulates the expression of CD86 and CD83 induced
      by NiSO(4) while it only affects the expression of CD83 induced by CoCl(2). IL-6
      production induced by NiSO(4) and CoCl(2) strongly depended on all MAPKs. IL
      12p40 synthesis after NiSO(4) treatment was regulated by both p38MAPK and JNK
      pathways whereas ERK may play an inhibitory role. Our results show that both
      NiSO(4) and CoCl(2) activate similar signaling pathways that are playing
      different roles in DC maturation depending on the hapten used.

PMID- 19101625
TI  - Divergence of the vertebrate sp1A/ryanodine receptor domain and SOCS box
      containing (Spsb) gene family and its expression and regulation within the mouse
      brain.
AB  - The Spsb family of genes encode well-conserved proteins of unknown function.
      Mammalian Spsb genes are likely the result of three separate duplication and
      divergence events during vertebrate evolution. The phylogenetic relationship
      along with expression and regulation of Spsb genes may offer insight into the
      evolution and function of this gene family in vertebrates. We have established
      that Spsb genes are expressed in numerous tissues, however their pattern and
      level of expression is tissue-dependent. Further, only Spsb1 is responsive to
      stress caused by ethanol exposure in the mouse brain, which suggests that Spsb
      genes have acquired different regulatory mechanisms. Analysis of cis-regulatory
      elements supports this, but also reveals some common regulatory modules involved
      in cell proliferation and stress response. Our results contribute to the growing
      body of data on the expression and function of Spsb genes, which serve as a model
      for studies on the origin, divergence and specialization of eukaryotic gene
      families.

PMID- 19101626
TI  - Effects of ceramide, ceramidase inhibition and expression of ceramide kinase on
      cytosolic phospholipase A2alpha; additional role of ceramide-1-phosphate in
      phosphorylation and Ca2+ signaling.
AB  - Ceramide and the metabolites including ceramide-1-phosphate (C1P) and sphingosine
      are reported to regulate the release of arachidonic acid (AA) and/or
      phospholipase A(2) (PLA(2)) activity in many cell types including lymphocytes.
      Recent studies established that C1P, a product of ceramide kinase, interacts
      directly with Ca(2+) binding regions in the C2 domain of alpha type cytosolic
      PLA(2) (cPLA(2)alpha), leading to translocation of the enzyme from the cytosol to
      the perinuclear region in cells. However, a precise mechanism for C1P-induced
      activation of cPLA(2)alpha has not been well elucidated; such as the
      phosphorylation signal caused by the extracellular signal-regulated kinases
      (ERK1/2) pathway, a downstream of the protein kinase C activation with 4beta
      phorbol myristate acetate (PMA), is required or not. In the present study, we
      showed that the increase in intracellular ceramide levels (exogenously added cell
      permeable ceramides and an inhibition of ceramidase by (1S,2R)-D-erythro-2-(N
      myristoylamino)-1-phenyl-1-propanol and the increase in C1P formation by
      transfection with the vector for human ceramide kinase significantly enhanced the
      Ca(2+) ionophore (A23187) -induced release of AA via cPLA(2)alpha's activation in
      CHO cells. Ceramides did not show additional effects on the release from the
      cells treated with the inhibitor of ceramidase. Ceramides and C2-C1P neither had
      effect on the intracellular mobilization of Ca(2+) nor the phosphorylation of
      cPLA(2)alpha in cells. A23187/PMA-induced release of AA was enhanced by ceramides
      and C2-C1P and by expression of ceramide kinase. Our findings suggest that C1P is
      a stimulatory factor on cPLA(2)alpha that is independent of the Ca(2+) signal and
      the PKC-ERK-mediated phosphorylation signal.

PMID- 19101627
TI  - The clinical spectrum of phosphomannose isomerase deficiency, with an evaluation
      of mannose treatment for CDG-Ib.
AB  - Phosphomannose isomerase (PMI) deficiency or congenital disorders of
      glycosylation type Ib (CDG Ib) is the only CDG that can be treated. Despite
      variable severity leading to dramatically different prognoses, clinical
      presentation is relatively homogeneous with liver and digestive features
      associated with hyperinsulinism and inconstant thrombosis. A feature of CDG is
      that coagulation factors are decreased. In our experience, mannose given orally
      at least 4 times per day not only transformed lethal CDG Ib into a treatable
      disease, but also improved the general condition and digestive symptoms of all
      reported patients but one. Liver disease, however, still persisted. Heparin can
      be used as an alternative to mannose in certain patients, particularly in the
      treatment of enteropathy.

PMID- 19101628
TI  - A comparison of two- and three-dimensional models for the simulation of the
      permeability of human stratum corneum.
AB  - The stratum corneum is the outermost layer of cells in mammalian epidermis. It is
      widely believed to play the key role for the barrier function of the skin. This
      study characterises how the cell geometry influences the permeability of the
      membrane. It is based on a diffusion model, which is evaluated using numerical
      simulation. Three different geometry concepts, i.e., ribbon, cuboid and
      tetrakaidekahedral type, in two and three space dimensions are compared. The
      results confirm that tetrakaidekahedral cells with an almost optimal surface-to
      volume ratio provide a barrier, in which a minimal amount of mass is used very
      effectively. Additionally, the study supplies tools to quantify this and links
      the results to the theory of homogenization.

PMID- 19101629
TI  - The role of porcine cytochrome b5A and cytochrome b5B in the regulation of
      cytochrome P45017A1 activities.
AB  - Male pigs are routinely castrated to prevent the accumulation of testicular 16
      androstene steroids, in particular 5alpha-androst-16-en-3-one (5alpha
      androstenone), which contribute to an off-odour and off-flavour known as boar
      taint. Cytochrome P450C17 (CYP17A1) catalyses the key regulatory step in the
      formation of the 16-androstene steroids from pregnenolone by the andien-beta
      synthase reaction or the synthesis of the glucocorticoid and sex steroids via
      17alpha-hydroxylase and C17,20 lyase pathways respectively. We have expressed
      CYP17A1, along with cytochrome P450 reductase (POR), cytochrome b5 reductase
      (CYB5R3) and cytochrome b5 (CYB5) in HEK-293FT cells to investigate the
      importance of the two forms of porcine CYB5, CYB5A and CYB5B, in both the andien
      beta synthase as well as the 17alpha-hydroxylase and C17,20 lyase reactions.
      Increasing the ratio of CYB5A to CYP17A1 caused a decrease in 17alpha-hydroxylase
      (p<0.013), a transient increase in C17,20 lyase, and an increase in andien-beta
      synthase activity (p<0.0001). Increasing the ratio of CYB5B to CYP17A1 also
      decreased 17alpha-hydroxylase, but did not affect the andien-beta synthase
      activity; however, the C17,20 lyase, was significantly increased. These results
      demonstrate the differential effects of two forms of CYB5 on the three activities
      of porcine CYP17A1 and show that CYB5B does not stimulate the andien-beta
      synthase activity of CYP17A1.

PMID- 19101630
TI  - Overexpression of wild-type human APP in mice causes cognitive deficits and
      pathological features unrelated to Abeta levels.
AB  - Transgenic mice expressing mutant human amyloid precursor protein (APP) develop
      an age-dependent amyloid pathology and memory deficits, but no overt neuronal
      loss. Here, in mice overexpressing wild-type human APP (hAPP(wt)) we found an
      early memory impairment, particularly in the water maze and to a lesser extent in
      the object recognition task, but beta-amyloid peptide (Abeta(42)) was barely
      detectable in the hippocampus. In these mice, hAPP processing was basically non
      amyloidogenic, with high levels of APP carboxy-terminal fragments, C83 and APP
      intracellular domain. A tau pathology with an early increase in the levels of
      phosphorylated tau in the hippocampus, a likely consequence of enhanced ERK1/2
      activation, was also observed. Furthermore, these mice presented a loss of
      synapse-associated proteins: PSD95, AMPA and NMDA receptor subunits and
      phosphorylated CaMKII. Importantly, signs of neurodegeneration were found in the
      hippocampal CA1 subfield and in the entorhinal cortex that were associated to a
      marked loss of MAP2 immunoreactivity. Conversely, in mice expressing mutant hAPP,
      high levels of Abeta(42) were found in the hippocampus, but no signs of
      neurodegeneration were apparent. The results support the notion of Abeta
      independent pathogenic pathways in Alzheimer's disease.

PMID- 19101631
TI  - Progranulin Leu271LeufsX10 is one of the most common FTLD and CBS associated
      mutations worldwide.
AB  - Mutations in the progranulin gene (PGRN) are a major cause of frontotemporal
      lobar degeneration (FTLD). Herein we estimated the contribution of the PGRN
      Leu271LeufsX10 mutation to FTLD and related disorders in the Brescia cohort. The
      PGRN Leu271LeufsX10 mutation was found in 31% of corticobasal syndrome (CBS), 29%
      of frontotemporal dementia with motorneuron disease (FTD-MND), 15% of behavioral
      variant frontotemporal dementia (FTD), 9.5% of primary progressive aphasia (PPA),
      2% dementia with Lewy bodies and 0% of progressive supranuclear palsy and
      multiple system atrophy cases. The prevalence strongly increased in familial
      forms (75% CBS, 50% FTD-MND, 27% FTD, 18% PPA): in our cohort this mutation is a
      major disease determinant for FTLD-related disorders with a prominent motor
      component. MAPT haplotype was demonstrated to be a disease modifier in PGRN
      Leu271LeufsX10 carriers: in H1H2 subjects the disease onset was earlier than in
      H2H2 individuals. Sequencing of the whole PGRN gene disclosed a previously
      described mutation (c.2T>C, Met1X) and three novel ones (c.709-3; c.1011delG,
      His340ThrfsX21; c.1021C>T, Gln341X) in single families. In the Brescia cohort,
      while MAPT mutations have low prevalence, mutations in PGRN were shown in 28% of
      familial FTLD and 75% of familial CBS cases. The PGRN Leu271LeufsX10 mutation
      becomes one of the most common mutations worldwide, since it was identified in 38
      patients belonging to 27 unrelated families.

PMID- 19101632
TI  - Determination of itopride hydrochloride in human plasma by RP-HPLC with
      fluorescence detection and its use in bioequivalence study.
AB  - A sensitive, selective and simple method using a precipitation of protein with
      10% perchloric acid, followed by high-performance liquid chromatography (HPLC)
      with fluorescence detection was developed for the determination of itopride
      hydrochloride in human plasma, using levofloxacin as the internal standard (IS).
      Chromatographic separation was obtained within 7.0 min using a reverse phase
      Hypersil BDS C(18) (250 mm x 4.6 mm, 5 microm) column and an isocratic mobile
      phase, constituting of a mixture of 0.1 mol/l ammonium acetate-methanol (30:70,
      v/v) flowing at 1.1 ml/min. The excitation and emission wavelengths were set at
      304 and 344 nm, respectively. The method was validated over the concentration
      range of 5 ng/ml to 1000.0 ng/ml. The lower limit of quantitation (LLOQ) was 5
      ng/ml. The extractive recovery of itopride hydrochloride from the biological
      matrix was more than 80.77%. The intra-day accuracy of the drug containing serum
      samples was more than 82.94% with a precision of 2.81-4.37%. The inter-day
      accuracy was 82.91% or more, with a precision of 6.89-9.54%. The limit we have
      used (70-143%) is based on the local regulatory authority (SFDA). The developed
      method was validated and successfully applied to bioequivalence studies of
      itopride hydrochloride in healthy male volunteers.

PMID- 19101633
TI  - Mitochondria in cancer: not just innocent bystanders.
AB  - The first half of the 20th century produced substantial breakthroughs in
      bioenergetics and mitochondria research. During that time, Otto Warburg observed
      abnormally high glycolysis and lactate production in oxygenated cancer cells,
      leading him to suggest that defects in mitochondrial functions are at the heart
      of malignant cell transformation. Warburg's hypothesis profoundly influenced the
      present perception of cancer metabolism, positioning what is termed aerobic
      glycolysis in the mainstream of clinical oncology. While some of his ideas stood
      the test of time, they also frequently generated misconceptions regarding the
      biochemical mechanisms of cell transformation. This review examines experimental
      evidence which supports or refutes the Warburg effect and discusses the possible
      advantages conferred on cancer cells by 'metabolic transformation'.

PMID- 19101634
TI  - Hexokinase-2 bound to mitochondria: cancer's stygian link to the "Warburg Effect"
      and a pivotal target for effective therapy.
AB  - The most common metabolic hallmark of malignant tumors, i.e., the "Warburg
      effect" is their propensity to metabolize glucose to lactic acid at a high rate
      even in the presence of oxygen. The pivotal player in this frequent cancer
      phenotype is mitochondrial-bound hexokinase [Bustamante E, Pedersen PL. High
      aerobic glycolysis of rat hepatoma cells in culture: role of mitochondrial
      hexokinase. Proc Natl Acad Sci USA 1977;74(9):3735-9; Bustamante E, Morris HP,
      Pedersen PL. Energy metabolism of tumor cells. Requirement for a form of
      hexokinase with a propensity for mitochondrial binding. J Biol Chem
      1981;256(16):8699-704]. Now, in clinics worldwide this prominent phenotype forms
      the basis of one of the most common detection systems for cancer, i.e., positron
      emission tomography (PET). Significantly, HK-2 is the major bound hexokinase
      isoform expressed in cancers that exhibit a "Warburg effect". This includes most
      cancers that metastasize and kill their human host. By stationing itself on the
      outer mitochondrial membrane, HK-2 also helps immortalize cancer cells, escapes
      product inhibition and gains preferential access to newly synthesized ATP for
      phosphorylating glucose. The latter event traps this essential nutrient inside
      the tumor cells as glucose-6-P, some of which is funneled off to serve as carbon
      precursors to help promote the production of new cancer cells while much is
      converted to lactic acid that exits the cells. The resultant acidity likely wards
      off an immune response while preparing surrounding tissues for invasion. With the
      re-emergence and acceptance of both the "Warburg effect" as a prominent phenotype
      of most clinical cancers, and "metabolic targeting" as a rational therapeutic
      strategy, a number of laboratories are focusing on metabolite entry or exit
      steps. One remarkable success story [Ko YH, Smith BL, Wang Y, Pomper MG, Rini DA,
      Torbenson MS, et al. Advanced cancers: eradication in all cases using 3
      bromopyruvate therapy to deplete ATP. Biochem Biophys Res Commun 2004;324(1):269
      75] is the use of the small molecule 3-bromopyruvate (3-BP) that selectively
      enters and destroys the cells of large tumors in animals by targeting both HK-2
      and the mitochondrial ATP synthasome. This leads to very rapid ATP depletion and
      tumor destruction without harm to the animals. This review focuses on the
      multiple roles played by HK-2 in cancer and its potential as a metabolic target
      for complete cancer destruction.

PMID- 19101636
TI  - Mitochondria as targets for cancer chemotherapy.
AB  - Heterogeneity of tumors dictates an individual approach to anticancer treatment.
      Despite their variability, almost all cancer cells demonstrate enhanced uptake
      and utilization of glucose, a phenomenon known as the Warburg effect, whereas
      mitochondrial activity in tumor cells is suppressed. Considering the key role of
      mitochondria in cell death, it appears that resistance of most tumors towards
      treatment can be, at least in part, explained by mitochondrial silencing in
      cancer cells. This review is devoted to the role of mitochondria in cell death,
      and describes how targeting of mitochondria can make tumor cells more susceptible
      to anticancer treatment.

PMID- 19101637
TI  - Centrifugal modulation of human LEP components to a task-relevant noxious
      stimulation triggering voluntary movement.
AB  - In the present study, we investigate the top-down centrifugal modulation of
      neural responses to a task-relevant noxious stimulation triggering voluntary
      movement by recording magnetoencephalography (MEG) and electroencephalography
      (EEG) simultaneously. An auditory warning signal was followed 2-3 s later by a
      noxious YAG laser stimulation as an imperative signal delivered to the left hand
      dorsum. Ten normal subjects performed three different conditions, Control,
      Movement, and Count. In Control, the subjects were asked to relax and rest
      quietly with no task. In Movement, the subjects extended the left index finger
      after imperative stimuli. In Count, the subjects counted the number of imperative
      stimuli silently. The amplitude of the N2 component recorded by EEG, which peaked
      about 220 ms after noxious stimulation, was significantly attenuated in Movement,
      but not in Count, compared to Control. The root-mean-square (RMS) from both
      hemispheres, and areal mean signal (AMS) amplitudes and the equivalent current
      dipole (ECD) strengths from SI/PPC and bilateral SII recorded at around 170 ms by
      MEG were not significantly different among the three conditions. In contrast, ECD
      strengths and AMS amplitudes from the anterior cingulate cortex (ACC), which
      showed a similar peak to the N2 component, were smaller in Movement than Control
      and Count. We therefore suspect that neural activities related to generator
      mechanisms of N2, especially including ACC, are inhibited by movement-related
      neural activities during the preparatory period. The present findings indicate a
      characteristic of pain-motor integration in a movement preparatory period.

PMID- 19101635
TI  - Homeostatic functions of the p53 tumor suppressor: regulation of energy
      metabolism and antioxidant defense.
AB  - The p53 tumor suppressor plays pivotal role in the organism by supervising strict
      compliance of individual cells to needs of the whole organisms. It has been
      widely accepted that p53 acts in response to stresses and abnormalities in cell
      physiology by mobilizing the repair processes or by removing the diseased cells
      through initiating the cell death programs. Recent studies, however, indicate
      that even under normal physiological conditions certain activities of p53
      participate in homeostatic regulation of metabolic processes and that these
      activities are important for prevention of cancer. These novel functions of p53
      help to align metabolic processes with the proliferation and energy status, to
      maintain optimal mode of glucose metabolism and to boost the energy efficient
      mitochondrial respiration in response to ATP deficiency. Additional activities of
      p53 in non-stressed cells tune up the antioxidant defense mechanisms reducing the
      probability of mutations caused by DNA oxidation under conditions of daily
      stresses. The deficiency in the p53-mediated regulation of glycolysis and
      mitochondrial respiration greatly accounts for the deficient respiration of the
      predominance of aerobic glycolysis in cancer cells (the Warburg effect), while
      the deficiency in the p53-modulated antioxidant defense mechanisms contributes to
      mutagenesis and additionally boosts the carcinogenesis process.

PMID- 19101638
TI  - Quantitative MRI predicts long-term structural and functional outcome after
      experimental traumatic brain injury.
AB  - In traumatic brain injury (TBI) the initial impact causes both immediate damage
      and also launches a cascade of slowly progressive secondary damage. The chronic
      outcome disabilities vary greatly and can occur several years later. The aim of
      this study was to find predictive factors for the long-term outcome using
      multiparametric, non-invasive magnetic resonance imaging (MRI) methodology and a
      clinically relevant rat model of fluid percussion induced TBI. Our results
      demonstrated that the multiparametric quantitative MRI (T(2), T(1rho), trace of
      the diffusion tensor D(av), the extent of hyperintense lesion and intracerebral
      hemorrhage) acquired during acute and sub acute phases 3 h, 3 days, 9 days and 23
      days post-injury has potential to predict the functional and histopathological
      outcome 6 to 12 months later. The acute D(av) changes in the ipsilateral
      hippocampus correlated with the chronic spatial learning and memory impairment
      evaluated using the Morris water maze (p<0.05). Similarly, T(1rho), T(2) and
      D(av) correlated with hippocampal atrophy and with histologically quantified
      neurodegeneration (p<0.01). The early lesion volume and quantitative MRI changes
      in the perilesional region prefigured the final lesion extent (p<0.01).
      Furthermore, the severity of acute intracerebral hemorrhage correlated with the
      final cortical atrophy (p<0.05), hippocampal atrophy (p<0.01), and also with the
      water maze performance (p<0.01). We conclude that, assessment of early
      quantitative MRI changes in the hippocampus and in the perifocal area may help to
      predict the long-term outcome after experimental TBI.

PMID- 19101639
TI  - Comparison of blocked and event-related fMRI designs for pre-surgical language
      mapping.
AB  - Language functional magnetic resonance imaging (fMRI) is a promising non-invasive
      technique for pre-surgical planning in patients whose lesions are adjacent to or
      within critical language areas. Most language fMRI studies in patients use
      blocked experimental design. In this study, we compared a blocked design and a
      rapid event-related design with a jittered inter-stimulus-interval (ISI) (or
      stochastic design) for language fMRI in six healthy controls, and eight brain
      tumor patients, using a vocalized antonym generation task. Comparisons were based
      on visual inspection of fMRI activation maps and degree of language
      lateralization, both of which were assessed at a constant statistical threshold
      for each design. The results indicated a relatively high degree of discordance
      between the two task designs. In general, the event-related design provided maps
      with more robust activations in the putative language areas than the blocked
      design, especially for brain tumor patients. Our results suggest that the rapid
      event-related design has potential for providing comparable or even higher
      detection power over the blocked design for localizing language function in brain
      tumor patients, and therefore may be able to generate more sensitive language
      maps. More patient studies, and further investigation and optimization of
      language fMRI paradigms will be needed to determine the utility and validity of
      this approach for pre-surgical planning.

PMID- 19101640
TI  - Near-tubular fiber bundle segmentation for diffusion weighted imaging:
      segmentation through frame reorientation.
AB  - This paper proposes a methodology to segment near-tubular fiber bundles from
      diffusion weighted magnetic resonance images (DW-MRI). Segmentation is simplified
      by locally reorienting diffusion information based on large-scale fiber bundle
      geometry. Segmentation is achieved through simple global statistical modeling of
      diffusion orientation. Utilizing a modification of a recent segmentation approach
      by Bresson et al. allows for a convex optimization formulation of the
      segmentation problem, combining orientation statistics and spatial
      regularization. The approach compares favorably with segmentation by full-brain
      streamline tractography.

PMID- 19101641
TI  - Patchy distributions belie morphological and genetic homogeneity in rosy-finches.
AB  - DNA sequence data often appear to contradict low-level avian taxonomy, which is
      usually based on patterns of external phenotypic similarity. We examined such an
      apparent contradiction in the Nearctic rosy-finches. On the basis of several
      phenotypic characters the finches were divided into three species congeneric with
      three Asian species. When Nearctic taxa were analyzed in a principal components
      analysis, 66.9% of phenotypic variation was explained by differences between the
      Bering Sea and continental populations, sexual dimorphism and a latitudinal
      cline. Our phylogenetic analysis of mitochondrial ND2 sequences revealed four
      clades among six species of rosy-finches. Three clades corresponded to three
      Asian species. The fourth clade included all three Nearctic species. Their
      haplotypes were not reciprocally monophyletic and the combined genetic
      variability of all Nearctic taxa was lower than in two of their Asian congeners.
      A Z-specific intron (ACO1I9) and an autosomal coding locus (MC1R) provided little
      additional phylogenetic information, most likely because of the longer
      coalescence times relative to ND2. Phylogeographic analyses of ND2 data revealed
      significant gene flow among neighboring localities regardless of their taxonomic
      assignment. Our analyses showed that DNA and phenotypic data are not in conflict,
      but rather complement each other, and together help clarify species limits. Our
      data are consistent with a single species in North America, not three.

PMID- 19101642
TI  - Genetic transfer of PNAS-4 induces apoptosis and enhances sensitivity to
      gemcitabine in lung cancer.
AB  - PNAS-4 has been demonstrated to induce apoptosis in U2OS cells. To evaluate its
      feasibility as a new strategy for cancer therapy, we analyzed its anti-tumor
      effect with or without gemcitabine in A549 lung cancer cells. MTT assay, Hoechst
      33258 staining and flow cytometric analysis were used to determine the
      cytotoxicity of PNAS-4 alone or plus gemcitabine. The anti-tumor efficacy was
      further investigated in vivo with nude mice. PNAS-4 plasmid/liposome complexes
      were injected by tail vein every 4 days. Gemcitabine was given ip on a weekly
      schedule for 4 weeks. PNAS-4 alone and plus gemcitabine induced apoptosis in A549
      cells in vitro. The xenograft lung cancer treated with PNAS-4 retarded growth
      compared with the empty vector. The combination of PNAS-4 with gemcitabine
      induced anti-tumor activity accompanied by an increase in apoptotic cells
      compared with PNAS-4 or gemcitabine alone. No other obvious toxicity was found.
      PNAS-4 therefore suppresses tumor growth in vivo and enhances sensitivity to
      gemcitabine. This suggests that the PNAS-4 gene could be a potential candidate
      for lung cancer therapy alone or in combination with gemcitabine.

PMID- 19101643
TI  - Redox thiol status plays a central role in the mobilization and metabolism of
      nitric oxide in human red blood cells.
AB  - We assessed the redox thiol status influence on nitric oxide (NO) metabolism and
      efflux in erythrocytes stimulated with acetylcholinesterase substrate
      (acetylcholine, ACh) and inhibitor (velnacrine maleate, VM). Erythrocyte
      suspensions from healthy donors were incubated with increasing concentrations of
      dithiothreitol (1-50microM), in the presence and absence of
      acetylcholine/velnacrine (10microM). Levels of NO, nitrite/nitrate, S
      nitrosohemoglobin, peroxynitrite and S-nitrosoglutathione were determined by
      spectrofluorimetric and spectrophotometric methods. Dithiothreitol significantly
      mobilized NO toward nitrite/nitrate and S-nitrosoglutathione, and decreased the
      amount of NO efflux. Both ACh/VM induce changes on the levels of erythrocyte
      nitrite/nitrate dependent on the DTT concentration. Higher levels of
      peroxynitrite and S-nitrosoglutathione were seen with velnacrine in presence of
      DTT 1 and 50microM. We concluded that dithiothreitol-induced activation of
      erythrocyte thiol status decreases NO efflux and allows greater intracellular NO
      mobilization onto different derivative molecules, both in the absence and
      presence of acetylcholinesterase substrate and inhibitor.

PMID- 19101644
TI  - Pax3 and Pax7 expression during myoblast differentiation in vitro and fast and
      slow muscle regeneration in vivo.
AB  - In this report, we focused on Pax3 and Pax7 expression in vitro during myoblast
      differentiation and in vivo during skeletal muscle regeneration. We showed that
      Pax3 and Pax7 were present in EDL (extensor digitorum longus) and Soleus muscle
      derived cells. These cells express in vitro a similar level of Pax3 mRNA,
      however, differ in the levels of mRNA encoding Pax7. Analysis of Pax3 and Pax7
      proteins showed that Soleus and EDL satellite cells differ in the level of Pax3/7
      proteins and also in the number of Pax3/7 positive cells. Moreover, Pax3/7
      expression was restricted to undifferentiated cells, and both proteins were
      absent at further stages of myoblast differentiation, indicating that Pax3 and
      Pax7 are down-regulated during myoblast differentiation. However, we noted that
      the population of undifferentiated Pax3/7 positive cells was constantly present
      in both in vitro cultured satellite cells of EDL and Soleus. In contrast, there
      was no significant difference in Pax3 and Pax7 during in vivo differentiation
      accompanying regeneration of EDL and Soleus muscle. We demonstrated that Pax3 and
      Pax7, both in vitro and in vivo, participated in the differentiation and
      regeneration events of muscle and detected differences in the Pax7 expression
      pattern during in vitro differentiation of myoblasts isolated from fast and slow
      muscles.

PMID- 19101645
TI  - Frequency-dependent power output and skeletal muscle design.
AB  - Cyclically contracting muscles provide power for a variety of processes including
      locomotion, pumping blood, respiration, and sound production. In the current
      study, we apply a computational model derived from force-velocity relationships
      to explore how sustained power output is systematically affected by shortening
      velocity, operational frequency, and strain amplitude. Our results demonstrate
      that patterns of frequency dependent power output are based on a precise balance
      between a muscle's intrinsic shortening velocity and strain amplitude. We discuss
      the implications of this constraint for skeletal muscle design, and then explore
      implications for physiological processes based on cyclical muscle contraction.
      One such process is animal locomotion, where musculoskeletal systems make use of
      resonant properties to reduce the amount of metabolic energy used for running,
      swimming, or flying. We propose that skeletal muscle phenotype is tuned to this
      operational frequency, since each muscle has a limited range of frequencies at
      which power can be produced efficiently. This principle also has important
      implications for our understanding muscle plasticity, because skeletal muscles
      are capable of altering their active contractile properties in response to a
      number of different stimuli. We discuss the possibility that muscles are
      dynamically tuned to match the resonant properties of the entire musculoskeletal
      system.

PMID- 19101646
TI  - Modulation of the early immune response against viruses by a teleostean
      interferon regulatory factor-1 (IRF-1).
AB  - We investigated the role of a teleostean interferon regulatory factor-1 (IRF-1)
      in the regulation of the fish immune system using Japanese flounder, Paralichthys
      olivaceus, as a model. Fish were intramuscularly vaccinated with a recombinant
      plasmid expressing the Japanese flounder IRF-1 (JF IRF-1) under the control of
      the cytomegalovirus immediate/early enhancer (CMV) promoter and were sampled at
      different days post-immunization. Peripheral blood leukocytes (PBLs) obtained
      from the JF IRF-1-vaccinated fish during the early stages post-vaccination had
      significantly elevated levels of nitric oxide (NO) and higher acid phosphatase
      (AP) activity compared with the control groups. Moreover, supernatants of PBLs
      obtained from the IRF-1-vaccinated fish contained cytokine-like substances as
      shown by their protective effect against hirame rhabdovirus (HIRRV) and viral
      hemorrhagic septicemia virus (VHSV) in two cell lines, hirame natural embryo
      (HINAE) cell line and epithelial papillosum of cyprini (EPC) cell line. Relative
      expression of an anti-viral gene, Mx was highest at the 7th day post-vaccination.
      Co-injection of JF IRF-1 with a DNA vaccine encoding the major capsid protein
      (MCP) gene of red seabream iridovirus (RSIV) resulted in elevated serum
      neutralization antibodies but was not significantly different from that in the
      fish vaccinated with the DNA vaccine alone. These results suggest that the JF IRF
      1 modulates the early immune response in fish and is a potential candidate as
      genetic adjuvant for vaccination.

PMID- 19101647
TI  - Tilapia sex determination: Where temperature and genetics meet.
AB  - This review deals with the complex sex determining system of Nile tilapia,
      Oreochromis niloticus, governed by the interactions between a genetic
      determination and the influence of temperature, shown in both domestic and wild
      populations. Naturally sex reversed individuals are strongly suggested in two
      wild populations. This can be due to the masculinising temperatures which some
      fry encounter during their sex differentiation period when they colonise shallow
      waters, and/or to the influence of minor genetic factors. Differences regarding
      a) thermal responsiveness of sex ratios between and within Nile tilapia
      populations, b) maternal and paternal effects on temperature dependent sex ratios
      and c) nearly identical results in offspring of repeated matings, demonstrate
      that thermosensitivity is under genetic control. Selection experiments to
      increase the thermosensitivity revealed high responses in the high and low
      sensitive lines. The high-line showed approximately 90% males after 2 generations
      of selection whereas the weakly sensitive line had 54% males. This is the first
      evidence that a surplus of males in temperature treated groups can be selected as
      a quantitative trait. Expression profiles of several genes (Cyp19a, Foxl2, Amh,
      Sox9a,b) from the gonad and brain were analysed to define temperature action on
      the sex determining/differentiating cascade in tilapia. The coexistence of GSD
      and TSD is discussed.

PMID- 19101648
TI  - Molecular cloning and biochemical characterization of the skin tyrosinase from
      Rana esculenta L.
AB  - Amphibian tyrosinases display unique and poorly understood properties such as
      seasonal activity variations, different activities in dorsal and ventral skin and
      the occurrence as inactive forms requiring proteolytic activation. For the first
      time we have sequenced and characterized Rana esculenta L. tyrosinase by
      functional expression of the cloned cDNA, and compared it with frog skin
      extracts. R. esculenta tyrosinase ORF is well conserved compared with tyrosinases
      of various sources. The amino acid similarities between the tyrosinases from R.
      esculenta and other amphibia range from 85% to 98%. Homology remains high with
      mammalian tyrosinases (65% identity with Homo sapiens, and 63% with Mus musculus)
      and with bird orthologues (66% identity with Gallus gallus). Tyrosinase was
      expressed in HEK293T cells as an active enzyme. Activity staining on non reducing
      SDS-PAGE revealed two bands around 63 and 68 kDa. R. esculenta skin extracts were
      mildly active and reached maximal activity upon protease treatment, revealing a
      high molecular weight dopa-positive band in the 200 kDa range and one of higher
      MW, after nagarse treatment, in activity stainings. The different behaviour of
      recombinant tyrosinase compared to skin extracts suggests formation in vivo of a
      multimeric complex.

PMID- 19101649
TI  - PPARdelta is pro-tumorigenic in a mouse model of COX-2-induced mammary cancer.
AB  - Cyclooxygenase-2 (COX-2), overexpressed in inflammatory conditions and cancer,
      regulates angiogenesis and tumorigenesis via the production of biologically
      active prostanoids. Previously, we showed that COX-2 over-expression in the
      mammary gland of transgenic mice induces an angiogenic switch and transforms the
      mammary epithelium into invasive mammary carcinoma. Since COX-2-derived
      prostanoids can activate the nuclear receptor PPARdelta, we crossed Ppardelta(-/
      ) mice with COX-2 transgenic mice in the FVB/N background. PPARdelta was
      expressed constitutively in the mammary gland of virgin, pregnant and lactating
      mice. Mammary hyperplasia and tumorigenesis in the COX-2 transgenic mice was
      markedly reduced in the Ppardelta(-/-) mice compared to their wild type
      counterparts. Analysis of the mammary tissues indicated that immunoreactive Ki
      67, cyclin D1 and phosphorylated histone 3 (Phospho H3) were reduced in
      Ppardelta(-/-) mice, suggesting that PPARdelta activation regulates cell
      proliferation in the mammary gland. We postulate that activation of the nuclear
      receptor PPARdelta by COX-2-derived prostanoids may be involved in the
      proliferation of mammary epithelial cells and therefore contribute to mammary
      cancer development.

PMID- 19101650
TI  - Assessment of the genotoxicity of Cu and Zn in raw and anaerobically digested
      slurry with the Vicia faba micronucleus test.
AB  - Genotoxicity of Cu and Zn was assessed by use of the micronucleus (MN) test on
      Vicia faba roots. Plants were exposed to various leachates of raw and
      anaerobically digested pig slurry, with maximum total concentrations of 200microM
      Cu and 600microM Zn. The results indicated stabilisation of the organic matter
      during anaerobic digestion of the slurry and bioconversion of some phytotoxic
      organic compounds (e.g. phenols or p-cresol), but did not show a relationship
      between Cu and Zn concentrations and MN frequency. Exposure of Vicia plants to
      binary inorganic solutions of Cu and Zn (CuSO(4)/ZnSO(4), 1:3) showed a
      significant micronucleus induction at concentrations of 40microM Cu and 120microM
      Zn and higher. When MN frequency was plotted against dissolved Cu (<0.45microm),
      applied as slurry or as CuSO(4), a single curve was obtained. At concentrations
      lower than 10microM, modulation of the genotoxic effect of Cu was found. At
      concentrations up to 150microM, MN induction increased significantly, while
      phytotoxic symptoms appeared at higher concentrations.

PMID- 19101651
TI  - Increased formation of gastric N(2)-ethylidene-2'-deoxyguanosine DNA adducts in
      aldehyde dehydrogenase-2 knockout mice treated with ethanol.
AB  - We analyzed an acetaldehyde-derived DNA adduct, N(2)-ethylidene-2'-deoxyguanosine
      (N(2)-Eti-dG) in stomach DNA of aldehyde dehydrogenase (Aldh)-2-knockout mice
      that were fed with alcohol to determine effects of alcohol consumption and Aldh2
      genotype on the level of DNA damage in stomach. Aldh2-active(+/+),
      heterozygote(+/-) and knockout(-/-) mice were fed 20% ethanol for 5 weeks, then
      the level of N(2)-Eti-dG in stomach was determined by liquid chromatography
      tandem mass spectrometry. The average N(2)-Eti-dG level in DNA from untreated
      mice was not significantly different among Aldh2 genotypes (2.0-3.1 adducts/10(7)
      bases), however, the average N(2)-Eti-dG level in DNA from ethanol-treated mice
      was 4.8+/-2.6 adducts/10(7) bases in Aldh2+/+ mice, 7.9+/-1.1 adducts/10(7) bases
      in Aldh2+/- mice, and 48.6+/-12.0 adducts/10(7) bases in Aldh2-/- mice,
      respectively. Our data clearly showed that alcohol drinking caused DNA damage in
      stomach, which was Aldh2 genotype-dependent in this experimental animal model.
      This result suggests that heavy-alcohol drinking and Aldh2 deficiency might be
      risk factors of stomach cancer.

PMID- 19101652
TI  - Miniaturisation effects in larvae and adults of Mikado sp. (Coleoptera:
      Ptiliidae), one of the smallest free-living insects.
AB  - We present the first morphological study of larvae and adults of Mikado sp. - one
      of the smallest known beetles and free-living insects (body length of adult is
      390-455microm). Morphological and developmental consequences of miniaturisation
      in Mikado and insects in general are discussed. We used histological sectioning,
      scanning electron microscopy, laser confocal microscopy and 3D-computer
      reconstruction. For the first time we report that according to the morphometric
      data of Mikado sp., at least some ptiliid beetles have three larval stages. We
      studied the muscular system of adults and larval stages. It is shown that ptiliid
      beetles have nearly the complete set of muscles found in larger staphyliniform
      beetles. Developmental and size dependent changes in the relative volume of
      different organs are addressed. All organ systems change allometrically in the
      development of Mikado sp. as well as in comparison with larger representatives of
      Ptiliidae and closely related groups of beetles, such as Staphylinidae. We
      conclude that the factors limiting miniaturisation are the size of the neural
      system, associated with the number and size of neurons, the mass of the skeleton,
      the egg size (free-living insects), and consequently the volume of the
      reproductive system.

PMID- 19101653
TI  - Structure, composition and properties of naturally occurring non-calcified
      crustacean cuticle.
AB  - Crustaceans are known for their hard, calcified exoskeleton; however some regions
      appear different in colour and opacity. These include leg and cheliped tips in
      the grapsid crab, Metopograpsus frontalis. The chelipeds and leg tips contain
      only trace levels of calcium but a significant mass of the halogens, chlorine
      (Cl) and bromine (Br). In contrast, the carapace is heavily calcified and
      contains only a trace mass of Cl and no Br. In transverse section across the non
      calcified tip regions of cheliped and leg the mass percent of halogens varies
      with position. As such, the exoskeleton of M. frontalis provides a useful model
      to examine a possible correlation of halogen concentration with the physical
      properties of hardness (H) and reduced elastic modulus (E(r)), within a chitin
      based matrix. Previously published work suggests a correlation exists between Cl
      concentration and hardness in similar tissues that contain a metal (e.g. zinc).
      However, in M. frontalis H and E(r) did not vary significantly across cheliped or
      leg tip despite differences in halogen concentration. The non-calcified regions
      of M. frontalis are less hard and less stiff than the carapace but equivalent to
      values found for insect cuticle lacking metals. Cheliped tips showed a complex
      morphological layering that differed from leg tips.

PMID- 19101654
TI  - Effects of o,p'-DDE, heptachlor, and 17beta-estradiol on vitellogenin gene
      expression and the growth hormone/insulin-like growth factor-I axis in the
      tilapia, Oreochromis mossambicus.
AB  - Effects of two endocrine disruptors, o,p'-DDE and heptachlor, and 17beta
      estradiol (E(2)) on vitellogenin (Vg) and the growth hormone (GH)/insulin-like
      growth factor-I (IGF-I) axis were examined in male tilapia. In the first
      experiment, fish were given 5 weekly injections of either E(2), o,p'-DDE or
      heptachlor (5 microg/g). E(2) treatment increased plasma Vg and hepatic
      expression of three Vg genes (Vgs A, B, and C) and estrogen receptor alpha
      (ERalpha), while reducing plasma levels of IGF-I and suppressing the expression
      of IGF-I, the GH receptor (GHR2) and the putative somatolactin receptor (GHR1).
      Neither pesticide greatly affected the other parameters examined, except for a
      significant reduction in expression of GHR2 and increased plasma IGF-I. In the
      second experiment, fish were given a single injection of o,p'-DDE or heptachlor
      (100 microg/g), or E(2) (5 microg/g) and sacrificed 5 days post-injection.
      Treatment with E(2) stimulated expression of all three Vg genes. Both o,p'-DDE
      and heptachlor increased expression of VgB, whereas only o,p'-DDE increased VgA
      expression. There was no effect of o,p'-DDE or heptachlor on VgC expression or
      plasma Vg levels. Treatment with o,p'-DDE and heptachlor as well as E(2)
      increased ERalpha and ERbeta transcript levels. Similarly, both pesticides
      increased GHR1 and IGF-I expression, whereas no significant effect of E(2) was
      observed on GHR1, GHR2 or IGF-I expression. These results indicate that o,p'-DDE
      and heptachlor have varying temporal and dose effects on modulation of Vg and the
      GH/IGF-I axis that are distinct from E(2).

PMID- 19101655
TI  - Hepatic and branchial glutathione S-transferases of two fish species: substrate
      specificity and biotransformation of microcystin-LR.
AB  - Liver and gills of roach (Rutilus rutilus) and silver carp (Hypophthalmichthys
      molitrix) were examined for glutathione S-transferases (GSTs) contents and their
      substrate specificity and capacity to biotransform microcystin-LR (MC-LR). GSTs
      and other glutathione (GSH) affine proteins were purified using a GSH-agarose
      matrix and separated by anionic chromatography (AEC). Substrate specificities
      were determined photometrical for 1-chloro-2,4-dinitrobenzene (CDNB), 1,2
      dichloro-4-nitrobenzene (DCNB), 4-nitrobenzyl chloride (pNBC) and ethacrynic acid
      (ETHA). Biotransformation rate of MC-LR was determined by high performance liquid
      chromatography (HPLC). Roach exhibited different hepatic and branchial GST
      activities for used substrates (DNB, pNBC and DCNB) compared to silver carp but
      not for ethacrynic acid. It suggests that, both fish species have similar amount
      of pi and/or alpha class, which were the dominant GST classes in liver and gills.
      Gills of both fish species contained a higher number of GST isoenzymes, but with
      lower activities and ability of MC-LR biotransformation than livers. GST
      isoenzymes from roach had higher activity to biotransform MC-LR (conversion rate
      ranging up to 268 ng MC-LR min(-1) mL(-1) hepatic enzyme) than that isolated from
      silver carp. Without any prior contact to MC-LR or another GST inducer, roach
      seems to be better equipped for microcystin biotransformation than silver carp.

PMID- 19101656
TI  - Perfluorooctane sulfonate (PFOS) toxicity in domestic chicken (Gallus gallus
      domesticus) embryos in the absence of effects on peroxisome proliferator
      activated receptor alpha (PPARalpha)-regulated genes.
AB  - Perfluorooctane sulfonate (PFOS) is a widely distributed industrial compound that
      has been detected in the eggs of various wild avian species. Laboratory studies
      have indicated that PFOS is embryotoxic to domestic chickens (Gallus gallus
      domesticus), but the mechanisms of toxicity in the developing avian embryo remain
      unknown. We recently demonstrated that PFOS acts as a peroxisome proliferator by
      causing increased expression of peroxisome proliferator activated receptor alpha
      (PPARalpha)-regulated genes in cultured primary chicken embryo hepatocytes. The
      present study examined whether PPARalpha-regulated genes were dose-dependently
      affected in chicken embryos exposed in ovo to PFOS. White leghorn chicken eggs
      were injected with 0.1, 5.0 or 100.0 microg PFOS/g egg into the air cell prior to
      incubation. Embryos were incubated until pipping, after which the expression of
      PPARalpha-regulated genes was measured in the liver tissue of surviving embryos
      using real-time reverse transcription polymerase chain reaction. A dose-dependent
      decrease in embryo pippability was observed with an LD50 of 93 microg/g (3.54
      microg/g-672,910 microg/g, 95% confidence interval). Hepatic PFOS concentrations
      increased concomitantly with dose. The PPARalpha-regulated genes measured were
      peroxisomal acyl CoA oxidase, bifunctional enzyme, liver fatty acid binding
      protein and peroxisomal 3-ketoacyl thiolase. PFOS exposure via egg injection
      prior to incubation did not affect the transcriptional activity of any of the
      assayed PPARalpha-regulated genes at any of the doses examined in day 21 chicken
      embryos.

PMID- 19101657
TI  - P-glycoprotein function in peripheral T lymphocyte subsets of myasthenia gravis
      patients: clinical implications and influence of glucocorticoid administration.
AB  - Myasthenia gravis (MG) is an autoimmune neuromuscular disorder with a chronic
      clinical course that requires long-term glucocorticoid (GC) therapy. A drug
      efflux pump, P-glycoprotein (P-gp), actively transports GC out of target cells,
      thereby reducing its efficacy. We evaluated the P-gp function of peripheral-blood
      mononuclear cells in 59 MG patients. P-gp function was estimated from a decrease
      in fluorescent P-gp substrate Rhodamine 123 and its inhibition by the
      conformation-sensitive UIC2 monoclonal antibody. P-gp function on CD8(+) T cells
      in 21 MG patients having experienced GC therapy was higher than that in 19 MG
      patients having no history of GC therapy (p=0.026). There was a significant
      correlation between P-gp function in CD3(+) (r=0.55, p=0.014) or CD4(+) (r=0.48,
      p=0.034) T cells and the total dose of prednisolone for treatment. P-gp function
      on CD4(+) T cells in MG patients who showed low responses to prednisolone therapy
      (n=8) was higher than that in patients who showed relatively high responses to
      prednisolone therapy (n=10) (p=0.045). These results suggest that higher P
      glycoprotein activity on CD3(+) or CD4(+) cells necessitated treatment with
      higher steroid doses in order to achieve a clinical response. The measurement of
      P-gp function on CD4(+) T cells is useful in the assessment of clinical response
      to GC therapy.

PMID- 19101658
TI  - Wnt signaling in Alzheimer's disease: up or down, that is the question.
AB  - Alzheimer's disease (AD) is a progressive neurodegenerative disorder,
      neuropathologically characterized by amyloid-beta (Abeta) plaques and
      hyperphosphorylated tau accumulation. AD occurs sporadically (SAD), or is caused
      by hereditary missense mutations in the amyloid precursor protein (APP) or
      presenilin-1 and -2 (PSEN1 and PSEN2) genes, leading to early-onset familial AD
      (FAD). Accumulating evidence points towards a role for altered Wnt/beta-catenin
      dependent signaling in the etiology of both forms of AD. Presenilins are involved
      in modulating beta-catenin stability; therefore FAD-linked PSEN-mediated effects
      can deregulate the Wnt pathway. Genetic variations in the low-density lipoprotein
      receptor-related protein 6 and apolipoprotein E in AD have been associated with
      reduced Wnt signaling. In addition, tau phosphorylation is mediated by glycogen
      synthase kinase-3 (GSK-3), a key antagonist of the Wnt pathway. In this review,
      we discuss Wnt/beta-catenin signaling in both SAD and FAD, and recapitulate which
      of its aberrant functions may be critical for (F)AD pathogenesis. We discuss the
      intriguing possibility that Abeta toxicity may downregulate the Wnt/beta-catenin
      pathway, thereby upregulating GSK-3 and consequent tau hyperphosphorylation,
      linking Abeta and tangle pathology. The currently available evidence implies that
      disruption of tightly regulated Wnt signaling may constitute a key pathological
      event in AD. In this context, drug targets aimed at rescuing Wnt signaling may
      prove to be a constructive therapeutic strategy for AD.

PMID- 19101659
TI  - A new large deletion in the DFNB1 locus causes nonsyndromic hearing loss.
AB  - Mutations in the GJB2 gene encoding the gap junction protein connexin 26 are
      responsible for up to 30% of all cases of autosomal recessive nonsyndromic
      hearing impairment (HI) with prelingual onset in most populations. The
      corresponding locus DFNB1, located on chromosome 13q11-q12, is also affected by
      three distinct deletions. These deletions extended distally to GJB2, which
      remains intact. We report a novel large deletion in DFNB1 observed in a patient
      presenting profound prelingual HI. This deletion was observed in trans to a GJB2
      mutated allele carrying the p.Val84Met (V84M) mutation and was shown to be
      associated with hearing loss. The deletion caused a false homozygosity of V84M in
      the proband. Quantification of alleles by quantitative fluorescent multiplex PCR
      (QFM-PCR) enabled us to study the breakpoints of the deletion. The deleted
      segment extended through at least 920kb and removed the three connexin genes
      GJA3, GJB2 and GJB6. The distal breakpoint inside intron 2 of CRYL1 gene differed
      from the breakpoints of the known DFNB1 deletions. This case highlights the
      importance of screening for large deletions in molecular studies of GJB2.

PMID- 19101660
TI  - Effect of taxol feeding on taxol and related taxane production in Taxus baccata
      suspension cultures.
AB  - To achieve a better understanding of taxol metabolism and accumulation in Taxus
      cell cultures, a T. baccata cell line growing for 20 days in a selected growth
      medium was treated at the beginning of the experiment with several concentrations
      of taxol (25, 50, 100 and 200mgL(-1)). Compared with an untreated control, all
      these taxol concentrations stimulated cell-associated taxol content (up to 32.7
      times in the presence of 200mgL(-1) exogenous taxol), although higher
      concentrations significantly depressed cell viability. DNA laddering analysis
      revealed that the viability reduction was not related to apoptosis, suggesting
      that taxol itself was the primary responsible factor. On the basis of RT-PCR
      expression analysis of genes encoding taxadiene synthase (ts) and 1-deoxy-d
      xylulose-5-phosphate synthase (dxs) from treated and nontreated T. baccata cell
      line cultures, it was observed that exogenous taxol clearly induced the mRNA
      levels of both taxane-related enzymes. Additionally, we found that exogenous
      taxol caused a considerable increase in taxadiene synthase activity, although in
      no case did this coincide with the highest levels of taxol observed at the end of
      the culture. The effect of exogenous taxol on the content of other related
      taxanes was also considered.

PMID- 19101661
TI  - Dynamics of backtracking long pauses of RNA polymerase.
AB  - The dynamics of backtracking long pauses by RNA polymerase is quantitatively
      studied based on our proposed model. Analytical formulas are obtained for the
      dependence of mean backtracking time and mean lifetime of backtracking long
      pauses on the binding affinity V(0) of RNAP to the DNA and RNA lattices, an
      important parameter for the transcription elongation complex. By comparison of
      the theoretically with experimentally obtained mean backtracking times, the value
      of binding affinity V(0) is predicted. Using the predicted V(0), the effects of
      external load on the mean backtracking time, on the lifetime of the backtracking
      long pauses and on the exit from the backtracking long pauses are studied. The
      results are in agreement with the available experimental data and, moreover, some
      predicted results are presented. In addition, using this V(0) we study the
      processivity of RNA polymerase under no and sideways forces.

PMID- 19101662
TI  - Quantification of bone tissue regeneration employing beta-tricalcium phosphate by
      three-dimensional non-invasive synchrotron micro-tomography--a comparative
      examination with histomorphometry.
AB  - PURPOSE: This methodical study presents a novel approach to evaluate the validity
      of two-dimensional histomorphometric measurements of a bone biopsy specimen after
      sinus floor elevation by means of high contrast, high resolution, three
      dimensional and non-destructive synchrotron micro-tomography (SCT). The aim of
      this methodical description is to demonstrate the potential of this new approach
      for the evaluation of bone biopsy samples. MATERIALS AND METHODS: Unilateral
      sinus grafting was carried out exemplarily in two patients using a combination of
      beta-tricalcium phosphate (beta-TCP) and autogenous bone chips. For the first
      patient a beta-TCP with 35% porosity and in the second with 60% porosity was
      used. At implant placement, 6 months after sinus grafting, a cylindrical specimen
      was biopsied from the augmented area. Subsequent to the histological embedding in
      resin the specimens were imaged using a SCT facility resulting in three
      dimensional (3-D) images with approximately 4 microm spatial resolution (1.5
      microm pixel size) for each patient's specimen. Subsequent to the SCT
      acquisition, tissue sections were prepared for histomorphometric analysis.
      RESULTS: Bone area fractions determined by two-dimensional (2-D) quantitative
      histomorphometry and by analysis of the corresponding 2-D slice from the SCT
      volume data were similar. For the first biopsy specimen (beta-TCP with 35%
      porosity), the bone area fractions were 53.3% and 54.9% as derived by
      histomorphometry and by analyzing a SCT slice, respectively. For the second
      biopsy specimen (beta-TCP with 60% porosity) the bone area fractions were 38.8%
      and 39% respectively. Although the agreement between the 2-D methods was
      excellent, the area fractions were somewhat higher than the volume fractions
      computed by 3-D image analysis on the entire SCT volume data set. The volume
      fractions were 48.8% (first biopsy specimen) and 36.3% (second biopsy specimen).
      CONCLUSION: Although the agreement between the 2-D methods is excellent in terms
      of computing the area fractions, the structural 3-D insight which can be derived
      from classical 2-D methods, including histomorphometric analysis is considerably
      limited. This fact is emphasized by the discrepancy between the measured areas
      and volume fractions.

PMID- 19101663
TI  - University students' notebook computer use.
AB  - Recent evidence suggests that university students are self-reporting experiencing
      musculoskeletal discomfort with computer use similar to levels reported by adult
      workers. The objective of this study was to determine how university students use
      notebook computers and to determine what ergonomic strategies might be effective
      in reducing self-reported musculoskeletal discomfort in this population. Two
      hundred and eighty-nine university students randomly assigned to one of three
      towers by the university's Office of Housing participated in this study. The
      results of this investigation showed a significant reduction in self-reported
      notebook computer-related discomfort from pre- and post-survey in participants
      who received notebook computer accessories and in those who received accessories
      and participatory ergonomics training. A significant increase in post-survey rest
      breaks was seen. There was a significant correlation between self-reported
      computer usage and the amount measured using computer usage software (odometer).
      More research is needed however to determine the most effective ergonomics
      intervention for university students.

PMID- 19101664
TI  - The effect of a resistance-training program on muscle strength, physical
      workload, muscle fatigue and musculoskeletal discomfort: an experiment.
AB  - The aim of the study was to investigate the effectiveness of a resistance
      training program on muscle strength of the back and neck/shoulder muscles,
      relative physical workload, muscle fatigue and musculoskeletal discomfort during
      a simulated assembly and lifting task. Twenty-two workers were randomized over an
      8-week resistance-training group, and a control group. Isokinetic muscle strength
      was assessed using the Cybex dynamometer, muscle fatigue was measured using EMG,
      and perceived discomfort was measured using a 10-point scale. At the follow-up,
      we found no effect of the resistance-training program on isokinetic muscle
      strength of the back and shoulder muscles. Furthermore, we did not find any
      effect on EMG data, nor on musculoskeletal discomfort during the simulated work
      tasks. However, trained workers performed the lifting tasks for a longer time
      before reporting considerable discomfort than those in the control group.

PMID- 19101665
TI  - Quantification of blockiness in pectins-A comparative study using vibrational
      spectroscopy and chemometrics.
AB  - The gelling properties of pectins are related not only to the degree of
      esterification (DE), but also to the distribution of the ester groups. In this
      study, we have examined an experimentally designed series of 31 pectins
      originating from the same mother pectin and de-esterified using combinations of
      two different enzymatic mechanisms. The potential of using infrared (IR), Raman,
      and near infrared (NIR) spectroscopies combined with chemometrics for reliable
      and rapid determination of the DE and distribution patterns of methyl ester
      groups in a designed set of pectin powders was investigated. Quantitative
      calibration models using partial least squares (PLS) regression were developed
      and compared. The calibration models for prediction of DE obtained on extended
      inverse signal correction (EISC)-treated spectra of all three spectroscopic
      methods yielded models with cross-validated prediction errors (RMSECV) between
      1.1%p and 1.6%p DE and correlation coefficients of 0.99. A calibration model
      predicting degree of random de-esterification (R) and block de-esterification (B)
      was developed for each spectroscopic method, yielding RMSECV values between 4.4
      and 6.7 and correlation coefficients (r) between 0.79 and 0.92. Variable
      selection using interval PLS (iPLS) significantly improved the prediction of R
      for IR spectroscopy, yielding RMSECV of 3.5 and correlation coefficients of 0.95.
      All three spectroscopic methods were able to distinguish the spectral patterns of
      pectins with different enzyme treatments in simple classification models by
      principal component analysis (PCA). Extended canonical variate analysis revealed
      one specific signal in the Raman (1045cm(-1)) spectrum and one significant area
      (1250-1400cm(-1)) in the IR spectrum which are able to classify the pectin
      samples according to the four different enzyme treatments. In both Raman and IR
      spectra, the signal intensity decreased in the sequence R-B>B>B-R>R>re-methylated
      pectin.

PMID- 19101666
TI  - Fingerprinting complex pectins by chromatographic separation combined with ELISA
      detection.
AB  - Enzyme-resistant pectin or modified hairy regions were subjected to size
      exclusion (HPSEC) and weak anion exchange (WAX) chromatography. Fractions
      collected after separation were tested for the presence of different pectic
      epitopes using the monoclonal antibodies LM2, LM5, LM6, and JIM7. Separation by
      HPSEC showed that based on molecular weight the different epitopes were
      restricted to distinct molecular weight populations. WAX chromatography resulted
      in an even better separation of the different pectic epitopes present. A clear
      separation between arabino galactan type II epitopes and the RG I side chains,
      (1,5)-alpha-l-arabinan and (1,4)-beta-d-galactan, could be established.
      Arabinogalactan type II was found in the first populations eluting off the WAX
      column. The observations made within the ELISA assays of the collected fractions
      could be confirmed by determination of the sugar composition of the individual
      populations obtained. The sugar composition of the AGII positive populations
      eluting off the WAX column shows the presence of significant amounts of rhamnose
      and galacturonic acid. Together with the delay on an anion exchanger, this
      observation indicates a possible linkage between RGI and AGII. The volume of the
      individual fractions collected provides enough material for a maximum of 20
      different antibodies to be tested from one analytical separation.

PMID- 19101667
TI  - A developmental dissociation between category and function judgments about novel
      artifacts.
AB  - Two studies investigated the relative importance of information about intended
      design and current use on judgments about the function (Experiment 1) or category
      (Experiment 2) of novel artifacts in preschool children and adults. Adults
      assigned function and name on the basis of information about design across all
      conditions, while children's decisions about function dissociated from decisions
      about category. Function judgments (in both 4 and 6-year-olds) were neutral
      between design and current use, both when the current use was idiosyncratic (e.g.
      performed by just one agent) and conventional (performed by many people;
      Experiment 1). By contrast, where category judgments were required for the very
      same objects (Experiment 2), children named according to design intentions - but
      only if the alternate function was idiosyncratic. Judging function and assigning
      category are thus cognitive tasks that draw on different information across
      development, a fact that should be captured by theories of developing artifact
      concept structure.

PMID- 19101668
TI  - Tasty non-words and neighbours: the cognitive roots of lexical-gustatory
      synaesthesia.
AB  - For lexical-gustatory synaesthetes, words trigger automatic, associated food
      sensations (e.g., for JB, the word slope tastes of over-ripe melon). Our study
      tests two claims about this unusual condition: that synaesthetic tastes are
      associated with abstract levels of word representation (concepts/lemmas), and
      that the first tastes to crystallise in early development are those triggered by
      food-names (e.g., apple tastes of apple; Simner & Ward, 2006). This concept/lemma
      based proposal is difficult to immediately reconcile with the finding that non
      words may also generate tastes (Ward, Simner, & Auyeung, 2005), since non-words
      have no concept/lemma representations. We manipulated the characteristics of non
      words to provide three types of evidence that non-word tastes in fact stem from
      real word neighbours: Non-words with neighbours (e.g., keach) are more likely to
      generate tastes than those with no neighbours (e.g., vilps); pseudo-homophone non
      words that are orthographically close to real words (e.g., peeple) are more
      likely to generate tastes than those that are more distant (baybee); and finally,
      the tastes of non-words are less consistent, and less intense, than those of real
      words. Additionally, we test the hypothesis that synaesthetic tastes develop
      initially from food-names by showing that non-words are more intensely flavoured
      if they are homophonic with food-names (e.g., toffie) versus non-foods (e.g.,
      peeple). From this we conclude that synaesthetic tastes develop from food-names,
      and that tasty non-words do not challenge a concept/lemma-based account of
      lexical-gustatory synaesthesia.

PMID- 19101669
TI  - Theoretical basis for identification of different anesthetic states based on
      routinely recorded EEG during operation.
AB  - In this paper, we present a new method to identify anesthetic states based on
      routinely recorded electroencephalogram (EEG). The identification of anesthesia
      stages are conducted using fast Fourier transform (FFT) and modified detrended
      fluctuation analysis (DFA) method. Simulation results demonstrate that this new
      method can clearly discriminate all five anesthesia states: very deep anesthesia,
      deep anesthesia, moderate anesthesia, light anesthesia and awake.

PMID- 19101670
TI  - LIPC variants in the promoter and intron 1 modify HDL-C levels in a sex-specific
      fashion.
AB  - We previously reported linkage for plasma levels of high-density lipoprotein
      cholesterol (HDL-C) on 15q21 in Caucasian families from the National Heart, Lung,
      and Blood Institute Family Heart Study (NHLBI FHS). Hepatic lipase gene (LIPC),
      which has a major role in lipoprotein metabolism, resides within the linkage
      region and constitutes an obvious candidate gene. While hepatic lipase is a known
      player in HDL metabolism, the relationship between common LIPC variants and HDL-C
      levels remains unclear. In the current study, we employed population-based and
      family-based tests of association with both quantitative HDL-C levels and a
      dichotomous dyslipidemia trait (affected men: HDL<40 mg/dL and women: HDL<50
      mg/dL, denoted as low HDL). We genotyped 19 tag-SNPs spanning 139.9 kb around the
      LIPC in the 591 families (2238 subjects). Strong association in a proxy-promoter
      5' SNP (rs261342) and HDL-C levels was detected in women, but not in men. The
      less common allele was associated with an increase of approximately 14% in HDL-C
      levels, and a decrease of approximately 30% in risk of low HDL. In addition,
      strong association in women of an intron 1 SNP (rs12593008) and low HDL and
      moderate association in men (rs8028759) with both HDL-C levels and low HDL
      phenotype were found and may represent either functional single nucleotide
      polymorphisms (SNPs), or more likely, SNPs in linkage disequilibrium with
      functional variants. Because of the association of lipid abnormalities with
      diabetes, and other lifestyle parameters, we also performed association analyses
      using different covariate adjustments as well as strategically selected sub
      samples. The sex-specific association of rs261342, rs12593008 or rs8028759
      remained substantially the same through these analyses. Finally, we found that a
      common haplotype was overtransmitted to offspring with low HDL-C. The sex
      specific associations found in our study could be due to the interactions with
      the endogenous hormonal environment, lifestyle and/or genetic factors, although
      the underlying physiologic mechanisms are not understood.

PMID- 19101671
TI  - Association between C-reactive protein gene haplotypes and C-reactive protein
      levels in Taiwanese: interaction with obesity.
AB  - OBJECTIVE: The level of C-reactive protein (CRP), an inflammatory marker that
      predicts future cardiovascular events, is a heritable trait. Our aim was to test
      the statistical associations between variations in the CRP gene and serum CRP
      levels in a Taiwanese population with interaction analysis. METHODS: A sample
      population of 617 Taiwanese subjects was enrolled. Five CRP single nucleotide
      polymorphisms (SNPs) previously reported to be associated with CRP level and with
      reasonable coverage of the CRP gene region were analyzed using polymerase chain
      reaction and restriction enzyme digestion or by TaqMan SNP Genotyping Assays.
      RESULTS: After adjusting for clinical covariates, minor alleles of 3 of the 5
      SNPs were associated with change in CRP level: rs3091244 and rs1205 were
      associated with increased CRP level (P=0.001 and P<0.001, respectively) and
      rs1800947 with decreased CRP level (P=0.003). Two haplotypes inferred from 5 SNPs
      (GCGCG and AAGCG) were associated with increased CRP level (P=0.017 and P<0.0001,
      respectively). Interaction analysis revealed interaction of obesity with CRP
      genotypes associated with high CRP level (interaction P=0.034 and 0.020 for SNPs
      rs2794521 and rs1800947, respectively). An effect of obesity on CRP level was
      also noted in haplotype interaction analysis with the association occurring
      predominantly in obese subjects (P=0.034). CONCLUSION: CRP polymorphisms are
      independently associated with increased or decreased CRP level in Taiwanese.
      Further, CRP genotypes/haplotypes interact with obesity to set CRP level. These
      findings have implications for the prediction of atherosclerotic disease.

PMID- 19101672
TI  - Micromechanical analyses of vertebral trabecular bone based on individual
      trabeculae segmentation of plates and rods.
AB  - Trabecular plates play an important role in determining elastic moduli of
      trabecular bone. However, the relative contribution of trabecular plates and rods
      to strength behavior is still not clear. In this study, individual trabeculae
      segmentation (ITS) and nonlinear finite element (FE) analyses were used to
      evaluate the roles of trabecular types and orientations in the failure initiation
      and progression in human vertebral trabecular bone. Fifteen human vertebral
      trabecular bone samples were imaged using micro computed tomography (microCT),
      and segmented using ITS into individual plates and rods by orientation
      (longitudinal, oblique, and transverse). Nonlinear FE analysis was conducted to
      perform a compression simulation for each sample up to 1% apparent strain. The
      apparent and relative trabecular number and tissue fraction of failed trabecular
      plates and rods were recorded during loading and data were stratified by
      trabecular orientation. More trabecular rods (both in number and tissue fraction)
      failed at the initiation of compression (0.1-0.2% apparent strain) while more
      plates failed around the apparent yield point (>0.7% apparent strain). A
      significant correlation between plate bone volume fraction (pBV/TV) and apparent
      yield strength was found (r(2)=0.85). From 0.3% to 1% apparent strain,
      significantly more longitudinal trabecular plate and transverse rod failed than
      other types of trabeculae. While failure initiates at rods and rods fail
      disproportionally to their number, plates contribute significantly to the
      apparent yield strength because of their larger number and tissue volume. The
      relative failed number and tissue fraction at apparent yield point indicate
      homogeneous local failure in plates and rods of different orientations.

PMID- 19101673
TI  - Impregnating titanium phosphate nanoparticles onto a porous cation exchanger for
      enhanced lead removal from waters.
AB  - Titanium phosphate (TiP) exhibits preferable sorption toward lead ion in the
      presence of competing calcium ions at high levels, however, it is present as fine
      or ultrafine particles and cannot be directly employed in fixed-bed or any flow
      through systems due to the excessive pressure drop and poor mechanical strength.
      In the present study a new hybrid sorbent TiP-001 was fabricated by impregnating
      titanium phosphate (TiP) nanoparticles onto a strongly acidic cation exchanger D
      001 for enhanced lead removal from waters. D-001 was selected as a host material
      mainly because of the Donnan membrane effect resulting from the immobilized
      sulfonic acid groups bound on the exchanger matrix, which would enhance
      permeation of the target metal cation prior to effective sequestration. TiP-001
      was characterized by transmission electron micrograph (TEM), X-ray diffraction
      (XRD), and pH-titration. Batch and column sorption onto TiP-001 was assayed to
      evaluate its performance as compared to the host exchanger D-001. Lead sorption
      onto TiP-001 is a pH-dependent process due to the ion-exchange nature, and its
      sorption kinetics follows the pseudo-second-order model well. Compared to D-001,
      TiP-001 displays highly selective lead sorption in the presence of competing
      calcium cations at concentration of several orders higher than the target metal.
      Fixed-bed sorption of a synthetic feeding solution indicates that lead retention
      by TiP-001 results in a conspicuous decrease of this toxic metal from 0.50 to
      below 0.010 mg/L (drinking water standard recommended by WHO). Moreover, its
      feasible regeneration by dilute HCl solution also favors TiP-001 to be a feasible
      sorbent for enhanced lead removal from water.

PMID- 19101674
TI  - Surface tension reduction (STR) in aqueous solutions of anionic surfactants with
      cobalt(III) complexes.
AB  - It has been observed that, at 25.0+/-0.1 degrees C, [Co(NH(3))(6)](ClO(4))(3),
      [Co(en)(3)](ClO(4))(3), [Co(bpy)(3)](ClO(4))(3), and [Co(phen)(3)](ClO(4))(3) in
      the regions of 1.25-5.00 mM aqueous solutions cause a significant surface tension
      reduction (STR) of water by the surfactants, sodium dodecylsulfate (SDS) and
      sodium dodecylbenzenesulfonate (SBS), suggesting the formation of the 1:1 and 1:2
      association complexes, {[complex](3+)(S(-))}(2+) and {[complex](3+)(S(-))(2)}(+)
      where [complex](3+)=[Co(NH(3))(6)](3+), [Co(en)(3)](3+), [Co(bpy)(3)](3+), or
      [Co(phen)(3)](3+), S(-)=DS(-) or BS(-). The effect of [Co(en)(3)](3+) on STR in
      SDS-water system is the largest due to a strong hydrophilic interaction between
      amino protons of [Co(en)(3)](3+) and sulfate oxygen atoms of DS(-). The effects
      of [Co(en)(3)](3+), [Co(bpy)(3)](3+), and [Co(phen)(3)](3+) on STR in SBS-water
      system are significant and almost same, meaning that the hydrophilic interaction
      between [Co(en)(3)](3+) and the sulfonate group is comparable to the hydrophobic
      interaction between [Co(bpy)(3)](3+) or [Co(phen)(3)](3+) and the phenyl group of
      BS(-). The Co(III) complexes of 1.25-5.00 mM are precipitated as
      {[complex](3+)(S(-))(3)} at 0.0295-0.173 mM of S(-). The precipitates,
      {[Co(bpy)(3)](3+)(S(-))(3)} and {[Co(phen)(3)](3+)(S(-))(3)} can be dissolved at
      higher molar ratio of [S(-)]/[complex(3+)] than 3.5 for SDS and 4.0 for SBS. This
      observation suggests that the aggregated premicelle [Co(bpy or phen)(3)](2)(DS)(
      )(7) or aggregated premicelle [Co(bpy or phen)(3)](BS)(-)(4) is formed.

PMID- 19101675
TI  - Adhesion between highly rough alumina surfaces: an atomic force microscope study.
AB  - The removal of contaminant particles in microelectronics processes now extends
      not only to the compounds themselves but also to the reactor pieces where they
      are fabricated. This raises new issues as both the particles and the reactor
      walls are highly rough and a maximum number of particles per unit area is
      tolerated. In this work we study the adhesion force of a sapphire particle onto
      alumina substrates of roughness ranging from 10 nm to 3 microm peak-to-peak on a
      5 microm x 5 microm area, in water. A contribution of this work is the prediction
      of the statistic of the adhesion force by a fast running numerical computation,
      without any adjustable parameters. The perspective is to be able to predict the
      best conditions for removing contaminant particles.

PMID- 19101676
TI  - Preparation of a microporous layered organic-inorganic hybrid nanocomposite using
      p-aminotrimethoxysilane and a crystalline layered silicate, ilerite.
AB  - The silylation of ilerite with p-aminophenyltrimethoxysilane (denoted as APhS)
      was conducted in order to attempt preparation of a layered organic-inorganic
      hybrid nanocomposite having interlayer microporosity, in which the APhS molecule
      bridges between the silicate layers using two heterofunctional groups containing
      an amino group and a methoxy one. The APhS molecules were successfully condensed
      and immobilized in the interlayer of the protonated ilerite. Chemical analysis
      and (29)Si solid-state NMR results indicated that the interlayer space was
      occupied by preferential condensation between the APhS molecules. Subsequent HCl
      treatment could remove the excess amounts of the oligomeric species of the APhS
      molecules. The removal brought about vacant spaces in the interlayer supported by
      the bridging of the residual APhS molecules. Furthermore, the immobilized APhS
      molecules had a significant influence on the surface properties of the resultant
      nanocomposite, which showed high toluene adsorptivity. Consequently, we found a
      means to construct a microporous, layered nanocomposite by the bridging of the
      organic spaces with two heterofunctional groups.

PMID- 19101677
TI  - Synthesis and thermotropic liquid crystalline properties of heterogemini
      surfactants containing a quaternary ammonium and a hydroxyl group.
AB  - A homologous series of novel heterogemini surfactants, (N,N-dimethyl-N-[3
      (alkyloxy)-2-hydroxypropyl]-alkylammonium bromide (referred to as C(m)OhpNC(n);
      m, n=10, 8; 12, 8; 14, 8; 16, 8; 14, 10; 12, 12 and 10, 14) were synthesized.
      Their thermotropic phase behavior was investigated by differential scanning
      calorimetry (DSC), polarizing optical microscopy (POM), infrared spectroscopy
      (IR) and X-ray diffraction (XRD). All the compounds showed high thermal stability
      and formed enantiotropic thermotropic smectic A liquid crystals. The mesophase
      region was sensitive to the overall length (m+n) of the two hydrophobic tails and
      was widened with increasing (m+n). When fixing the overall length of the two
      hydrophobic tails (m+n=24), the liquid crystal region was affected little by the
      dissymmetry of the two hydrophobic chains. The combination of IR and XRD results
      suggested the cis-configuration of the alkyl chain and the alkoxy chain with
      respect to the extended N-CH(2)-CH(OH) skeleton in both crystal lattice and
      liquid crystal mesophase. The folding of the alkoxy chain at the carbon atom
      connecting the hydroxyl group led to the hydrogen bonding between the hydroxyl
      and the Br(-) counterion, which is beneficial to stabilizing the liquid crystal
      phase.

PMID- 19101678
TI  - Hysteresis in the individual and competitive sorption of cadmium, copper, and
      lead by various soil horizons.
AB  - Investigations of the sorption of heavy metals by soils often involve a fast ion
      exchange process followed by a more sorbate-specific slow process. Desorption and
      sorption isotherms often fail to coincide, thus showing real or artifactual
      hysteresis, and failure to conform to conventional models generally prevents
      meaningful comparison of the hysteretic behavior of different sorbates in
      different soils. In the work described here, the irreversibility of the sorption
      of Cd, Cu, and Pb from single-metal and multimetal solutions by samples of 20
      soil horizons was evaluated in terms of a hysteresis index, defined as the ratio
      between the values obtained in desorption and sorption experiments for an
      affinity measure defined in previous work, K(r). Sorption of these metals from
      both types of solution was more irreversible in the more basic soils, and its
      other chief determinants were CIC(e), Mn oxides content, and, except for Cd,
      organic matter content. The least sorbed metal was invariably Cd.

PMID- 19101679
TI  - Electrokinetic modeling of metal oxides.
AB  - The focus of this study is the electrokinetic transport of metal oxide colloidal
      particles. These transport properties include electrophoretic mobility and the
      primary electroviscous effect of dilute suspensions of spherical particles that
      may contain a "gel layer" of uniform density on their outer surface. Charge on
      the surface or in the gel layer is assumed to arise from specific protonation,
      deprotonation, or complex formation reactions of oxide sites. Charge regulation,
      or the modulation of the equilibrium constants due to high absolute charge
      densities, is examined. Both the electrostatics and electrokinetic transport
      properties are solved numerically within the framework of the continuum-primitive
      model. With regards to the electrokinetics, detailed account is taken of the
      finite size of the particle as well as the "electrophoretic effect" and the
      "relaxation effect." The methodology is then applied to two metal oxide systems:
      Ludox (a silica sol) and goethite. The charge density, electrophoretic mobility,
      and primary electroviscous effect of Ludox at pH 8.7 in KCl salt solutions, can
      be well explained by a gel layer model that expands as the salt concentration is
      lowered. A spherical model containing no gel layer is unable to account for the
      electrophoretic mobility of goethite in 0.01 M KNO(3). However, a "sparse" gel
      layer model that contains 7.5% of the charge sites and consists of 96% solvent
      can account for both the experimental charge density and mobility over the pH
      range 4.0 to 11.0.

PMID- 19101680
TI  - Preparation of honeycomb scaffold with hierarchical porous structures by core
      crosslinked core-corona nanoparticles.
AB  - The preparation of honeycomb scaffold with hierarchical controllable porous
      structures is reported. The ABA three block amphiphilic copolymer PS-b-P(St-Alt
      AMn)-b-PS was synthesized through reversible addition fragmentation chain
      transfer polymerization (RAFT) and subsequently self-assembled to core-corona
      nanoparticles with the middle block P(St-Alt-AMn) as the core and two side block
      PS as the corona. The formed core-corona nanoparticles were further crosslinked
      through the reaction of amino diphenyl methane with anhydride in chains. The core
      crosslinked core-corona nanoparticles were used as the building block to
      fabricate the controllable porous scaffold with hierarchical structure. The
      micrometer level honeycomb mesostructures can be obtained by an inverse emulsion
      template method which is consisted in the formation of the high internal phase
      ratio emulsions (HIPRE) while the nanometer level pores are formed by the close
      packed core-corona block copolymer nanoparticles. As carboxylic group is formed
      in the crosslink step of the core, the growth factor can be easily incorporated
      into the matrix in order for the growth of the cell in the tissue engineering
      application. This kind of hierarchical honeycomb structure is an ideal candidate
      for the tissue engineering and drug delivery applications.

PMID- 19101681
TI  - Synthesis of ZSM-5 with intracrystal or intercrystal mesopores by polyvinyl
      butyral templating method.
AB  - Three facile routes were utilized to synthesize ZSM-5 materials with intracrystal
      or intercrystal mesopores, where the polyvinyl butyral gel served as mesopore
      directing template. The three routes were divided into two synthesis strategies:
      the hydrothermal treatment of silica/PVB composite and re-crystallization of
      preformed zeolite precursor with the assistance of PVB gel. The fabrication of
      silica/PVB composite was accomplished by two routes including sol-gel process and
      impregnation method. The resulting composite was undergone hydrothermal
      treatment. During the crystallization PVB was occluded in the ZSM-5 crystal,
      creating intracrystal mesopores in the zeolite. The last route for the synthesis
      of mesoporous ZSM-5 was realized by re-crystallization of preformed ZSM-5 zeolite
      in the presence of PVB. This route involved the pre-crystallization of the
      amorphous aluminosilicate to produce the pre-formed ZSM-5 precursor. Upon further
      crystallization of the mixture of PVB gel and pre-formed ZSM-5, the ZSM-5
      precursor was transformed into ZSM-5 aggregate of nanocrystals, while the PVB gel
      was occluded in the ZSM-5 particles. Removal of the template generated the
      typical microporosity associated with ZSM-5 structure along with intercrystal
      mesoporosity produced from the PVB. The mesoporous ZSM-5 exhibited enhanced
      catalytic activity in the toluene disproportionation and transalkylation with
      C(9) and C(10) aromatics.

PMID- 19101682
TI  - Temperature-responsive polymer brush constructed on a colloidal gold monolayer.
AB  - Polymers of 2-(2-methoxyethoxy)ethyl methacrylate (MDM) were prepared by atom
      transfer radical polymerization using 2-(2'-bromoisobutyroyloxy)ethyl disulfide
      as initiator. An aqueous solution of the disulfide-carrying polymer (DT-PMDM)
      turned to be opaque above certain temperature (22 degrees C for DT-PMDM
      (M(n)=1.69x10(4))), which was corresponding to the lower critical solution
      temperature (LCST) of the polymer. The disulfide-carrying polymer could be
      accumulated on the surface of gold colloid as a polymer brush as confirmed by the
      increase in absorbance at 550 nm ascribable to the localized surface plasmon
      resonance (LSPR). Furthermore, the polymer brush could also be constructed on a
      monolayer of colloidal gold that had been deposited on a glass plate beforehand.
      The PMDM brush on both the free and surface-confined gold colloids showed
      definite temperature responsiveness in the absorbance at 550 nm. Moreover, non
      specific adsorption of various proteins to the surface of polymer brush on the
      glass plate was examined by the absorption increase at 550 nm. The PMDM brush,
      which had been prepared with the DT-PMDM pretreated with NaBH(4), did not adsorb
      lysozyme significantly below the LCST of the polymer chain, whereas substantially
      adsorbed the protein above the LCST. These results suggest usability of the
      polymer brushes with pendent omega-methoxy oligo(ethylene glycol) groups to coat
      various materials for biomedical applications.

PMID- 19101683
TI  - Electrolyte ion effects on Cd2+ binding at Al2O3 surface: specific synergism
      versus bulk effects.
AB  - Cd(2+) binding on gamma-Al(2)O(3) was studied in the presence of the common
      electrolyte ions Mg(2+), SO(4)(2-), and NO(3)(-) at high and low concentrations.
      Direct measurements were performed for Cd(2+) as well as for electrolyte ion
      adsorption as a function of pH. The experimental data reveal that Cd(2+) binding
      on gamma-Al(2)O(3) is modulated by the electrolyte ions in a complex manner. At
      high electrolyte concentration, Cd(2+) uptake by gamma-Al(2)O(3) is inhibited.
      Theoretical analysis by a surface complexation model shows that this effect can
      be attributed partially to bulk, ionic strength, and effect of the electrolyte,
      but the most significant inhibition is due to direct competition between Mg(2+)
      and Cd(2+) ions for the [triple bond]SO(-) surface sites of gamma-Al(2)O(3). At
      low concentration of electrolyte ions, Cd(2+) uptake by gamma-Al(2)O(3) can be
      enhanced due to synergistic co-adsorption of Cd(2+) and electrolyte anions,
      particularly SO(4)(2-) and to a lesser extent NO(3)(-). The theoretical analysis
      shows that this co-adsorption is due to formation of ternary surface species
      ([triple bond]SOH(2)SO(4)Cd) and ([triple bond]SOH(2)NO(3)Cd) which enhance Cd
      uptake at pH values well below the point of zero charge of the gamma-Al(2)O(3).

PMID- 19101684
TI  - Association between blood pressure and carotid intima-media thickness.
AB  - OBJECTIVE: To investigate the association between blood pressure and carotid
      intima-media thickness (IMT) in healthy adolescents. STUDY DESIGN: Study
      participants included 285 first-year high school students (mean age, 15.2 years)
      at a rural high school in Korea. Systolic and diastolic blood pressure (SBP and
      DBP) were measured with an oscillometric automated sphygmomanometer. The carotid
      arteries were evaluated with high-resolution B-mode ultrasound scanning. IMT
      value was determined with the average of the maximal IMT at each common carotid
      artery. Increased IMT was defined as sex-specific top quartile. The odds ratio
      (OR) for increased IMT per 1 SD increase of SBP and DBP was estimated after
      adjusting for age, sex, body mass index, waist circumference, fasting glucose
      level, and total/high-density lipoprotein cholesterol ratio. RESULTS: Adjusted OR
      for increased IMT was 1.70 (P = .003) per 12.4 mm Hg SBP and 1.25 (P = .125) per
      7.0 mm Hg DBP. When the analyses were performed by sex, increased IMT was
      associated with both SBP (OR, 2.67; P = .003) and DBP (OR, 1.68; P = .019) in
      girls, but it was not associated with either SBP (OR, 1.46; P = .093) or DBP (OR,
      0.99; P = .972) in boys. CONCLUSION: These results suggest that higher blood
      pressure level may be associated with increased carotid IMT in apparently healthy
      adolescents.

PMID- 19101685
TI  - Plasma plant sterol levels do not reflect cholesterol absorption in children with
      Smith-Lemli-Opitz syndrome.
AB  - OBJECTIVE: To test the hypothesis that there is a correlation between the ratio
      of plant sterols to cholesterol in plasma and dietary cholesterol absorption in
      children with Smith-Lemli-Opitz syndrome (SLOS), a cholesterol synthesis
      disorder. STUDY DESIGN: We obtained measurements of cholesterol absorption with a
      direct radioisotope cholesterol absorption method during 9 visits of children
      with SLOS. We measured plasma sterols in 22 children with SLOS and 16 control
      children, and we measured dietary intake of cholesterol and sitosterol (n=11
      SLOS). RESULTS: The correlations of 2 plasma plant sterol ratios
      (sitosterol/cholesterol and campesterol/cholesterol) with direct cholesterol
      absorption measurement were poor (R= -0.33 and R= -0.25, respectively),
      significantly lower than the published correlation in adults (R=0.73; P< .02).
      CONCLUSIONS: Although the ratios of plant sterols to cholesterol in plasma has
      been used as a surrogate for cholesterol absorption in adults and children, these
      ratios may not accurately reflect cholesterol absorption in children with SLOS.
      These ratios should not be used as a surrogate for cholesterol absorption in
      children without further validation.

PMID- 19101686
TI  - Vascular dysfunction in glycogen storage disease type I.
AB  - OBJECTIVE: To determine cardiovascular disease risk in a larger cohort of
      patients with glycogen storage disease (GSD) I through the use of noninvasive
      measures of arterial function and anatomy. STUDY DESIGN: Carotid intima media
      thickness (IMT), radial artery tonometry, and brachial artery reactivity were
      performed in 28 patients with GSD I (13F/15M, mean age 23 years) and 23 control
      subjects (19F/4M, mean age 23 years). RESULTS: The primary outcome measure, mean
      left distal IMT was greater in the GSD cohort (0.500+/-0.055 mm) than in the
      control group (0.457+/-0.039 mm) (P= .002, adjusted for age, sex, and body mass
      index). Mean augmentation index measured by radial artery tonometry was higher in
      the GSD cohort (16.4%+/-14.0%) than in the control group (2.4%+/-8.7%) (P< .001).
      No significant difference was observed between mean brachial artery reactivity in
      the GSD cohort (6.3%+/-4.9% change) versus control subjects (6.6%+/-5.1% change)
      (P= .46). CONCLUSIONS: GSD I is associated with arterial dysfunction evident by
      increased IMT and augmentation index. Patients with GSD I may be at increased
      risk for cardiovascular disease.

PMID- 19101687
TI  - Impact of haloperidol and quetiapine on the expression of genes encoding
      antioxidant enzymes in human neuroblastoma SH-SY5Y cells.
AB  - Antipsychotics are known to alter antioxidant activities in vivo. Therefore, the
      aim of the present study was to examine in the human neuroblastoma SH-SY5Y cell
      line the impact of a typical (haloperidol) and an atypical (quetiapine)
      antipsychotic on the expression of genes encoding the key enzymes of the
      antioxidant metabolism (Cu, Zn superoxide dismutase; Mn superoxide dismutase;
      glutathione peroxidase; catalase) and enzymes of the glutathione metabolism
      (gamma-glutamyl cysteine synthetase, glutathione-S-transferase, gamma
      glutamyltranspeptidase, glutathione reductase). The cells were incubated for 24h
      with 0.3, 3, 30 and 300microM haloperidol and quetiapine, respectively; mRNA
      levels were measured by polymerase chain reaction. In the present study, we
      observed mostly significant decreases of mRNA contents. With respect to the key
      pathways, we detected mainly effects on the mRNA levels of the hydrogen peroxide
      detoxifying enzymes. Among the enzymes of the glutathione metabolism, glutathione
      S-transferase- and gamma-glutamyltranspeptidase-mRNA levels showed the most
      prominent effects. Taken together, our results demonstrate a significantly
      reduced expression of genes encoding for antioxidant enzymes after treatment with
      the antipsychotics, haloperidol and quetiapine.

PMID- 19101688
TI  - Co-expression of urokinase with haptoglobin in human carcinomas.
AB  - BACKGROUND: We have shown that colon and breast cancer contains large amounts of
      urokinase (uPA), and that these cells are the actual sites of its synthesis. We
      isolated a large complex molecule consisting of the beta-chain of uPA, both
      chains of haptoglobin (Hp), and part or all of an NCAM-like molecule. The
      question arose whether it would be possible to show the presence of Hp in the
      same cells where uPA was found. MATERIALS AND METHODS: Human colon and breast
      adenocarcinomas were investigated for expression of Hp and uPA by
      immunohistochemistry. Fluorescence in situ hybridization was used to identify the
      cells of origin of these antigens. RESULTS: Hp was expressed in 8 of 11 colon
      adenocarcinomas, and in 10 of 12 breast tumors. uPA was demonstrable on the cell
      membrane and in the cytoplasm of all 11 colon adenocarcinomas studied, and
      cytoplasmic uPA-mRNA was found in all cases. While uPA was also detected in some
      stromal and inflammatory cells, Hp was present abundantly in such cells, as well
      as in capillary endothelial cells. Hp-mRNA was also found in both colon and
      breast tumors wherever the antigens were expressed. CONCLUSIONS: uPA and Hp are
      produced by the cancer cells and are not taken up by stromal elements. While the
      role of uPA in the malignant process is well documented, that of Hp is largely
      unexplored. Its ubiquity, shown here, suggests that it is also involved in some
      aspects of that process.

PMID- 19101689
TI  - Alloantigen-pulsed host dendritic cells induce T-cell regulation and prolong
      allograft survival in a rat model of hindlimb allotransplantation.
AB  - BACKGROUND: Composite tissue allotransplantation is restricted due to the risks
      presented by long-term therapeutic immunosuppression. This study is conducted to
      investigate whether treatment with recipient immature dendritic cells (DCs)
      pulsed with donor alloantigens can prolong allograft survival and induce T-cell
      regulation in a rodent model. MATERIALS AND METHODS: Orthotopic hindlimb
      transplants from Brown-Norway (RT1(n)) to Lewis (RT1(1)) rats were performed (day
      0). DCs were propagated from the recipient bone marrow and pulsed with the donor
      alloantigen lysate. Group 1 (control group) did not receive any treatment. Groups
      2 and 3 received cyclosporine A (CsA) at a concentration of 10 and 16 mg.kg(
      1).day(-1), respectively, on days 0-20 following composite tissue
      allotransplantation. Group 4 received antilymphocyte serum (i.p. administered 4 d
      before and 1 d after transplantation) therapy. Group 5 received combined
      treatment with CsA (10 mg.kg(-1).day(-1), days 0-20) and donor alloantigen-pulsed
      recipient DCs (i.v. administered on days 7, 14, and 21). Group 6 received
      combined treatment with CsA (10 mg.kg(-1).day(-1) on days 0-20), antilymphocyte
      serum (administered i.p. 4 d before and 1 d after transplantation), and DCs
      (administered i.v. on days 7, 14, and 21). Graft rejection was defined as
      epidermolysis/desquamation of the donor skin. The mixed lymphocyte reaction was
      performed to determine the donor T-cell reactivity. Tissue samples were biopsied
      to analyze the histological changes, and flow cytometry was performed to quantify
      the donor T-cells. RESULTS: Allograft survival was significantly prolonged (>200
      d) in Group 6 when compared with the other groups (P < 0.001). The mixed
      lymphocyte reaction performed for Group 6 revealed hyporesponsiveness of the T
      cells to donor alloantigens. Flow cytometric analysis in Group 6 revealed a
      significant increase in the percentage of CD4(+)/CD25(+) and CD4(+)/foxP3(+) T
      cells expression, and significant increase in the percentage of donor cells
      (RT1(n)) in the recipient peripheral blood. Immunohistochemical staining of allo
      skin revealed a significant increase in the proportion of CD25(+) cells in the
      subcutaneous and dermis layers in Group 6, as compared to other groups.
      CONCLUSION: Treatment with donor alloantigen-pulsed recipient immature DCs in
      combination with transient immunosuppression prolongs allograft survival and
      induced tolerance by inducing T-cell hyporesponsiveness to donor alloantigens and
      increasing the CD4(+)/CD25(+) T-cell population.

PMID- 19101690
TI  - Novel murine model for colon cancer: non-operative trans-anal rectal injection.
AB  - BACKGROUND: This study was conducted to develop a modified murine model of colon
      cancer that is non-operative. Currently, the most accurate orthotopic murine
      model of colon cancer requires an invasive procedure involving cecal injection of
      colon cancer cells and therefore limits the ability to perform immunological
      studies subsequent to cecal resections. MATERIALS AND METHODS: Murine colon
      cancer (CT26) cells were injected submucosally into the distal, posterior rectum
      of BALB/c mice. Care was taken not to pass transmurally into the pelvic cavity.
      Different magnifications (10x versus 100x) were used for injection, and primary
      tumor growth and metastatic disease were studied. RESULTS: In the initial study,
      3/7 mice injected using 10x magnifications had notable, large tumor originating
      from the rectal wall, and histology revealed that all excised tumors were poorly
      differentiated adenocarcinoma. In the second study, 8/10 mice injected using 100x
      magnifications had notable tumor originating from the rectal well, and 4/8 mice
      had abnormal lung tissue with pathological evidence of hemorrhagic pulmonary
      edema. The use of 10x magnification resulted in 43% tumor take. In sharp
      contrast, 80% tumor take was observed with 100x magnification. The overall
      success of tumor take was 65% using the trans-anal rectal injection model.
      CONCLUSIONS: Our modified orthotopic murine model of colon cancer offers an
      alternative non-operative murine model for colon cancer and is less invasive than
      the traditional orthotopic model (i.e., cecal injection). This model may allow
      for more accurate investigations of inflammation and immune responses to surgical
      intervention without the influence of previous abdominal surgery.

PMID- 19101691
TI  - Mind the gap: workforce disparities and global health.

PMID- 19101692
TI  - Factors in fellowship selection: effect of services and fellows.
AB  - PURPOSE: General Surgery residents are increasingly pursuing fellowships. We
      examine whether perceived subspecialty content, dedicated services, and fellows
      impact fellowship choices. METHODS: Specialty content was assessed through a
      survey linking 228 operations to 9 content areas. The presence of dedicated
      services and fellows and the post-residency activities of graduates 1997-2006
      were collected from 2 program directors. RESULTS: A total of 75% of residents (26
      University of Mississippi, UM; 22 Vanderbilt University, VU) completed surveys.
      Five dedicated services and 2 fellowships at UM and VU were identical; VU had an
      additional 4 services and 3 fellowships. UM and VU residents similarly associated
      184 operations (81%) with General Surgery. Agreement was not linked to services
      or fellows. A total of 44% of UM graduates and 68% of VU graduates pursued
      fellowships. The top choice at UM was Plastic/Hand (14%, versus 6% VU) and
      Oncology/Endocrine at VU (19%, versus 2% UM). Differences in specialties selected
      could not be linked consistently to dedicated services or fellows. CONCLUSION:
      Dedicated services and fellows appear to have little impact on fellowship
      specialty selection by chief residents. There may be a generic effect of
      dedicated services favoring fellowship versus no fellowship. Differential faculty
      mentoring skills may influence specific fellowship choices.

PMID- 19101693
TI  - Induction of antitumor response by in vivo allogeneic major histocompatibility
      complex gene transfer using electroporation.
AB  - BACKGROUND: Most malignancies lack tumor-associated antigens, which are
      recognized by T-lymphocytes through major histocompatibility complex (MHC)
      molecules, and seem to evade host immunological defense. In this study, we
      investigated whether allogeneic MHC gene transfer into the low-antigenic tumor
      might induce cell-mediated immunity, and provide an immunotherapeutic effect in
      vivo. MATERIALS AND METHODS: Mammary adenocarcinoma cells (MAT B III) originated
      from an F344 rat (RT1A(l)) were transfected with a plasmid DNA encoding RT1A(a)
      (pcMRT1A) in vitro. Cytolytic T-cell response was then evaluated using F344
      splenocytes. Furthermore, pcMRT1A-liposome complex was injected into the MAT B
      III tumors grown in F344 rats, followed by a series of eight electrical pulses
      with a electroporator, every other d for total of four times. The tumor size and
      survival of animals were evaluated thereafter. RESULTS: The expression of RT1A(a)
      on the tumor cells induced cytolytic T-cell response in vitro. Intratumor
      injection of pcMRT1A-liposome complex followed by in vivo electroporation
      markedly generated biological response, including increased interferon-gamma (IFN
      gamma) expression and a large number of infiltrated cells in the tumor. Inhibited
      tumor growth, even complete tumor regression, was observed, resulting in
      prolonged survival time. CONCLUSIONS: Direct transfer of allogeneic MHC gene into
      the tumor by in vivo electroporation could induce a cell-mediated immune response
      against the introduced antigens, resulting in local IFN-gamma production. This
      initial response may bring about the subsequent immunological response even to
      the unmodified tumor cells through cytokines such as IFN-gamma, resulting in the
      marked tumor regression.

PMID- 19101694
TI  - Dry lab practice leads to improved laparoscopic performance in the operating
      room.
AB  - BACKGROUND: Research has demonstrated that practice in surgical simulators leads
      to improved performance in that simulator. Our hypothesis is that skills acquired
      in simulators are transferable to the operating room. MATERIALS AND METHODS:
      Twenty-three laparoscopically naive surgical interns performed two standardized
      tasks in a simulator: pegboard transfer and intracorporeal knot tying.
      Performance was measured using a validated scoring system. On the same day as
      this initial assessment, subjects were videotaped performing two tasks in a live
      porcine model: running the small bowel and intracorporeal knot tying. Performance
      in the porcine model was measured using a modified version of a validated skills
      assessment tool by two blinded experts. Following a 6-wk proficiency-based dry
      lab laparoscopic training course, task performance was re-evaluated. No interval
      live operative laparoscopic experience occurred between the first and second
      assessment. RESULTS: After training, mean pegboard transfer scores increased from
      118.7 to 181.8 (theoretical maximum = 300; P < 0.01). Dry lab knot tying scores
      increased from 294.7 to 459.0 (theoretical maximum = 600, P < 0.01). In the
      porcine model, scores for the bowel running task increased from 8.5 to 13.5
      (maximum score = 20 for both porcine tasks, P < 0.01). Knot tying scores
      increased from 7.3 to 14.3 (P < 0.01). CONCLUSION: Practice in a simulator leads
      to improved performance in that simulator and in a live operative model. We
      believe that this is evidence that laparoscopic skills developed in a dry
      laboratory setting are transferable to the operating room.

PMID- 19101696
TI  - Prediction of nonsentinel lymph node metastasis in malignant melanoma.
AB  - BACKGROUND: Sentinel lymph node biopsy (SLNB) is the standard at many
      institutions caring for melanoma patients. Patients with positive SLNB results
      are currently offered completion lymph node dissection (CLND) of the affected
      lymph node basin. This procedure entails considerable morbidity and is often
      applied to patients with shortened life expectancies. Because 80% of CLNDs yield
      no additional positive nodes and there is no proof that CLND leads to survival
      improvement, criteria are needed to limit this procedure to those most likely to
      harbor nonsentinel lymph node (SLN) metastases. METHODS: A retrospective review
      of 349 cases of melanoma from January 1999 to April 2007 that underwent sentinel
      lymph node biopsy at a single institution was done. Statistical analysis was used
      to compare two subgroups of patients: a positive CLND group and a negative CLND
      group. These two groups were compared with regards to multiple variables related
      to patient demographics, primary tumor characteristics, and SLN tumor burden.
      RESULTS: Age and total size of SLN tumor deposit were the factors with the
      strongest correlation with CLND positivity. By applying a risk score model that
      uses the cutoff values of age 55 y and SLN tumor deposit of 5 mm, it is possible
      to predict CLND positivity in SLN-positive melanoma patients. CONCLUSION: The
      likelihood of CLND positivity in SLN-positive melanoma patients can be predicted
      from two criteria readily available: size of SLN tumor deposit and patient age.

PMID- 19101695
TI  - Patterns of gelatinase activation induced by injury in the murine femoral artery.
AB  - BACKGROUND: Intimal hyperplasia remains the principal lesion in the development
      of restenosis after vessel wall injury. Modulation of the extracellular matrix by
      proteases is a pivotal component of the response to injury. The aim of this study
      is to characterize the changes in gelatinase (MMP-2/TIMP-2 and MMP-9/TIMP-1)
      systems in a murine model. METHODS: The murine femoral wire injury model was used
      in which a microwire is passed through a branch of the femoral and used to denude
      the common femoral artery. Pluronic gel was used to apply a proteass inhibitor
      (GM6001) to the exterior of the vessels. Specimens were perfusion-fixed and
      sections were stained with hematoxylin and eosin and Movat's stain such that
      morphometry could be performed by using an ImagePro system. Additional specimens
      of femoral artery were also harvested and snap frozen for Western blotting and
      zymography to allow for the study of gelatinase expression and activation.
      Contralateral vessels were used as controls. RESULTS: MMP-2 activity increased
      significantly at day 1, peaked again at day 7, and then showed a continual
      decline in activity to day 56. MMP-9 activity peaked early at day 3 and declined
      thereafter. Protein expression for both MMP-2 and MMP-9 increased significantly
      after injury and both were maximal at day 14. There was an initial decrease in
      TIMP-1 and TIMP-2 expression and activity after injury until day 5. Both
      expression and activation gradually increased thereafter to level out by day 21
      and correlated well with the early increases in MMP-2 and MMP-9 activity and
      their subsequent decline. Local application of protease inhibitor (GM6001) within
      a pluronic gel decreased cell proliferation, and at 14 d there was a decrease in
      intimal hyperplasia. CONCLUSIONS: These data demonstrate that femoral wire injury
      in the mouse is associated with a time-dependent increase in gelatinase activity.
      Cell proliferation is associated with increased MMP-2/MMP-9 activity and
      decreased TIMP-2/TIMP-1 activity, whereas migration is associated with increased
      in MMP-2 activity. Modulation of proteases and their inhibitors control the
      vessels' response to injury.

PMID- 19101697
TI  - A novel murine island skin flap for ischemic preconditioning.
AB  - BACKGROUND: Ischemia reperfusion injury is a well-known phenomenon affecting skin
      flap viability. One method to improve flap viability is ischemic preconditioning.
      Previous murine flap models used random flaps. We developed a single pedicle
      island skin flap which allows us to create true ischemia by clamping the single
      pedicle. Our first aim was to describe a novel murine skin flap model with a
      definable, reproducible injury. Our second aim was to test the usefulness of this
      model by demonstrating mitigation of injury via ischemic preconditioning.
      MATERIALS AND METHODS: Dorsal lateral thoracic artery pedicle island skin flaps
      (3.5 x 1.5 cm) were elevated in 39 male C57/BL6 mice: a Control group (n = 7), 10
      h of ischemia (n = 21), and Preconditioning (2 cycles of 20 min ischemia: 20
      minutes reperfusion) + 10-h ischemia (n = 11). After flap elevation, a silicon
      sheet barrier was placed. The axial pedicles were occluded, and the flaps were
      inset with 6-0 prolene. In all mice, ischemia was followed by 1 wk of
      reperfusion. At 1 wk, percent necrosis was measured and an analysis of variance
      was performed. RESULTS: The percent of flap necrosis was 1.1% +/- 1.11% in
      controls. Animals that were subjected to 10 h of ischemia developed 33.14% +/-
      7.23% necrosis. Preconditioned animals that underwent 10 h of ischemia
      demonstrated a 43% reduction in necrosis (18.82% +/- 5.68%). There was a
      statistically significant difference among all groups (P < or = 0.001).
      CONCLUSION: Rat models have been the standard for skin flap experiments. We have
      developed a novel murine single pedicle island skin flap model with reproducible
      injury. This model has numerous advantages, including ease of handling, low cost,
      appropriateness for biomedical studies, and the availability of genetically
      altered animals. We also confirmed this model's usefulness in a study of
      mitigation of ischemia reperfusion injury through ischemic preconditioning.

PMID- 19101698
TI  - A new intercostal artery management strategy for thoracoabdominal aortic aneurysm
      repair.
AB  - OBJECTIVE: The purpose of this study is to describe a new approach for addressing
      the intraoperative management of intercostal arteries during thoracoabdominal
      aortic aneurysm (TAAA) repair, using preoperative spinal MRA for detection of
      intercostal arteries supplying the anterior spinal artery. METHODS: Patients
      undergoing TAAA repair from August 2005 to September 2007 were included. Spinal
      artery MRA was performed to identify the anterior spinal artery, the artery of
      Adamkiewicz, and its major intercostal source artery (SA-AAK). Intraoperative
      spinal cord protection was carried out using standard techniques. Important
      intercostal arteries were either preserved or reimplanted as a button patch after
      removing aortic clamps. Demographic and perioperative data were collected for
      review. Analysis was performed with Fisher's exact test or Student's t-test,
      where applicable, using SAS ver. 8.0 (Cary, NC). RESULTS: Spinal artery MRA was
      performed in 27 patients. The SA-AAK was identified in 85% of preoperative
      studies. Open or endovascular repair was performed in 74% and 26% of patients,
      respectively. The SA-AAK was preserved or reimplanted in 13 (65%) of patients who
      underwent open repair. A mean of 1.67 (range 1-3) intercostal arteries were
      reimplanted. All patients undergoing endovascular repair necessitated coverage of
      the SA-AAK. No patient developed immediate or delayed paraplegia. Longer mean
      operative times in the reimplanted cohort were not statistically significant (330
      versus 245 min, P = 0.1). CONCLUSION: The SA-AAK identified by MRA can be
      preserved or safely reimplanted after TAAA repair. Further study is warranted to
      determine if selective intercostal reimplantation can reduce the risk of
      immediate or delayed paraplegia.

PMID- 19101699
TI  - Significance and expression of atypical protein kinase C-iota in human
      hepatocellular carcinoma.
AB  - BACKGROUND AND OBJECTIVE: Previous studies have indicated that abnormal
      expression of atypical protein kinase C (aPKC-iota) plays a critical role in
      occurrence and progression of malignant tumor. This study analyzed the
      correlation of aPKC-iota with clinicopathology in hepatocarcinoma and Cyclin E
      and investigated molecular mechanisms of invasion and metastasis of
      hepatocellular carcinoma. MATERIALS AND METHODS: The expression of the aPKC-iota
      gene was examined by reverse transcription-polymerase chain reaction in 7
      specimens of normal liver tissues and 43 of hepatoma and adjacent tissues.
      Expression of aPKC-iota and Cyclin E protein was detected using
      immunohistochemistry and Western blot. Finally, we analyzed the correlation of
      aPKC-iota with clinicopathologic characteristics and invasion of hepatoma.
      RESULTS: The expression value (0.844 +/- 0.315) of aPKC-iota gene is obviously
      higher in hepatoma than the value (0.530 +/- 0.217) in adjacent tissues and the
      value (0.372 +/- 0.130) in normal tissue (P = 0.009). The positive expression
      rate (58.1%) of aPKC-iota protein in hepatoma is remarkably higher than the rate
      (23.3%) of adjacent tissues. The expression of aPKC-iota has a positive
      correlation with the expression of Cyclin E, differentiation degree, and invasion
      of tumor (P < 0.05). CONCLUSIONS: Differentiation degree and invasion of hepatoma
      are related to the expression of aPKC-iota, which plays an important role in
      invasion and metastasis of hepatoma.

PMID- 19101700
TI  - Inflammatory myopathies with mitochondrial pathology and protein aggregates.
AB  - OBJECTIVES: To compare the clinical course and muscle biopsy features of
      polymyositis with mitochondrial pathology (PM-Mito) to inclusion body myositis
      (IBM) and steroid-responsive inflammatory myopathies (polymyositis). METHODS: We
      compared clinical, laboratory and myopathologic features in a retrospective study
      of patients with PM-Mito (23), IBM (26) and polymyositis (12). RESULTS: Selective
      weakness in the quadriceps or finger flexors was common in PM-Mito (62%) and IBM
      (87%). Weakness progressed more slowly in PM-Mito than in IBM. PM-Mito patients
      with more rapidly progressive weakness had more cytochrome oxidase negative
      muscle fibers. There was no history of benefit from corticosteroid treatment in
      any PM-Mito or IBM patients. B-cell foci were absent in IBM and PM-Mito. LC3, an
      autophagy marker, and alphaB-crystallin were common in aggregates in PM-Mito and
      IBM, but not polymyositis. SMI-31 and TDP-43 positive aggregates were common in
      IBM but not in PM-Mito or polymyositis. beta-amyloid showed no differences in
      aggregates among the three groups. CONCLUSIONS: PM-Mito and IBM may be part of
      the same disease spectrum. PM-Mito has more slowly progressive weakness than IBM
      and rarely has TDP-43 or SMI-31 staining aggregates in muscle fibers. The most
      frequent proteins in aggregates in both PM-Mito and IBM are LC3, an autophagy
      marker, and alphaB-crystallin. Alterations in autophagic degradation pathways may
      be a common pathogenic mechanism in PM-Mito and IBM. In pathologically typical
      polymyositis, staining for mitochondrial enzyme activity, aggregates and B-cells
      helps to distinguish PM-Mito from inflammatory myopathy syndromes that are more
      likely to respond to corticosteroid treatment.

PMID- 19101701
TI  - Efficacy of idebenone for respiratory failure in a patient with Leigh syndrome: a
      long-term follow-up study.
AB  - Respiratory failure can be the direct cause of death in patients with Leigh
      syndrome. Unfortunately, no effective treatment strategy is available. Here, we
      report successful treatment of a patient with Leigh syndrome using idebenone, a
      derivative of coenzyme Q-10. The patient's brainstem function, especially
      respiratory function, improved after idebenone treatment. Idebenone may be worth
      trying in patients with Leigh syndrome.

PMID- 19101702
TI  - Protection against paraquat and A53T alpha-synuclein toxicity by cabergoline is
      partially mediated by dopamine receptors.
AB  - Both genetic and environmental factors are thought to be involved in the
      aetiology of Parkinson's disease (PD). Oxidative damage, mitochondrial and
      proteasomal dysfunction, and inflammatory change are considered to participate in
      PD pathogenesis. Dopamine agonists are used in the symptomatic treatment of PD
      but attention has recently also been focussed on their potential for use in
      slowing disease progression. We have studied the protective actions of the D2
      dopamine agonist cabergoline in toxin (paraquat) and genetic (wild-type and
      mutant [A53T] alpha-synuclein) models of PD using SHSY-5Y cells. Cabergoline
      increased glutathione content, reduced free radical production and caspase-3
      activation, increased mitochondrial membrane potential and ameliorated cell death
      in SHSY-5Y cells exposed to paraquat and this action was inhibited in part by D2
      receptor blockade. Cabergoline also reduced the toxicity of wild-type and mutant
      alpha-synuclein expression following paraquat exposure by similar mechanisms.
      These results confirm the protective action of cabergoline in reducing cell death
      in two separate genetic and environmental model systems of PD.

PMID- 19101703
TI  - Study of a Taiwanese family with oculopharyngeal muscular dystrophy.
AB  - BACKGROUND: Oculopharyngeal muscular dystrophy (OPMD) is a late onset autosomal
      dominant muscle disorder. OPMD is caused by a short trinucleotide repeat
      expansion encoding an expanded polyalanine tract in the polyadenylate binding
      protein nuclear 1 (PABPN1) gene. We identified and characterized a PABPN1
      mutation in a Taiwanese family with OPMD. METHODS: The phenotypic and genotypic
      characteristics of all subjects were evaluated in a Taiwanese OPMD family.
      Genetic alterations in the PABPN1 gene were identified using PCR and DNA
      sequencing. RESULTS: Ten subjects with OPMD (6 symptomatic and 4 asymptomatic)
      within the Taiwanese family carried a novel mutation in the PABPN1 gene. The
      normal (GCG)6(GCA)3GCG sequence was replaced by (GCG)6(GCA)(GCG)4(GCA)3GCG due to
      an insertion of (GCG)4GCA into the normal allele in the Taiwanese OPMD subjects.
      CONCLUSIONS: In contrast to a single GCG expansion in most of OPMD patients in
      the literature, an insertion of (GCG)4GCA in the PABPN1 gene was found in the
      Taiwanese OPMD subjects. The identification of this mutation appears to support
      the molecular mechanism of unequal cross-over of two PABPN1 alleles.

PMID- 19101704
TI  - Effects of copper and the sea lice treatment Slice on nutrient release from
      marine sediments.
AB  - Copper-based antifoulant paints and the sea lice treatment Slice are widely used,
      and often detectable in the sediments beneath farms where they are administered.
      Ten-day, whole sediment mesocosm experiments were conducted to examine how
      increasing sediment concentrations of copper or Slice influenced final water
      column concentrations of ammonium-nitrogen (NH(4)-N), nitrate+nitrite-nitrogen
      (NO(X)-N) and phosphate-phosphorus (PO(4)-P) in the presence of the non-target,
      benthic organisms Corophium volutator and Hediste diversicolor. Nominal sediment
      concentrations of copper and Slice had significant effects on the resulting
      concentrations of almost all nutrients examined. The overall trends in nutrient
      concentrations at the end of the 10-day incubations were highly similar between
      the trials with either copper or Slice, irrespective of the invertebrate species
      present. This suggests that nutrient exchange from the experimental sediments was
      primarily influenced by the direct effect of copper/Slice dose on the sediment
      microbial community, rather than the indirect effect of reduced
      bioturbation/irrigation due to increased macrofaunal mortality.

PMID- 19101705
TI  - Azetidine-2-carboxylic acid in the food chain.
AB  - Azetidine-2-carboxylic acid (Aze) 1 is a non-protein amino acid present in sugar
      beets and in table beets (Beta vulgaris). It is readily misincorporated into
      proteins in place of proline 2 in many species, including humans, and causes
      numerous toxic effects as well as congenital malformations. Its role in the
      pathogenesis of disease in humans has remained unexplored. Sugar beet
      agriculture, especially in the Northern Hemisphere, has become widespread during
      the past 150 years, and now accounts for nearly 30% of the world's supply of
      sucrose. Sugar beet byproducts are also used as a dietary supplement for
      livestock. Therefore, this study was undertaken as an initial survey to identify
      Aze-containing links in the food chain. Herein, we report the presence of Aze 1
      in three sugar beet byproducts that are fed to farm animals: sugar beet molasses,
      shredded sugar beet pulp, and pelleted sugar beet pulp.

PMID- 19101706
TI  - Development of the UK food samples surveillance system.
AB  - OBJECTIVES: To describe the UK Food Surveillance System (FSS UK) currently in
      operation in Scotland and Northern Ireland, and being introduced UK-wide,
      particularly in relation to the development, scope and roll-out of the system.
      STUDY DESIGN: Pilot questionnaire, followed by pilot information technology (IT)
      based study and subsequent roll-out. METHODS: A paper-based trial of data
      collection was introduced, followed by an IT-based pilot and the subsequent
      development of an IT-based system and an Internet-based resource. A project
      working group and specific user groups were formed to assist the dedicated
      project team to progress the project. The groups' compositions reflect the
      interests of the various partner organizations, including the involvement of the
      Food Standards Agency. RESULTS: Following the successful pilot study, Health
      Protection Scotland was commissioned by the Food Standards Agency to develop and
      roll-out FSS UK to councils and their partner laboratories throughout the UK
      within a 3-year period. CONCLUSION: The development of FSS UK provides the
      opportunity to compare and contrast national food sample data, highlight emerging
      food-related trends and provide an early warning system for food-related issues.

PMID- 19101708
TI  - Nasal architecture of Paradolichopithecus arvernensis (late Pliocene, Seneze,
      France) and its phyletic implications.

PMID- 19101707
TI  - SV40 DNA replication: from the A gene to a nanomachine.
AB  - Duplication of the simian virus 40 (SV40) genome is the best understood
      eukaryotic DNA replication process to date. Like most prokaryotic genomes, the
      SV40 genome is a circular duplex DNA organized in a single replicon. This small
      viral genome, its association with host histones in nucleosomes, and its
      dependence on the host cell milieu for replication factors and precursors led to
      its adoption as a simple and powerful model. The steps in replication, the viral
      initiator, the host proteins, and their mechanisms of action were initially
      defined using a cell-free SV40 replication reaction. Although our understanding
      of the vastly more complex host replication fork is advancing, no eukaryotic
      replisome has yet been reconstituted and the SV40 paradigm remains a point of
      reference. This article reviews some of the milestones in the development of this
      paradigm and speculates on its potential utility to address unsolved questions in
      eukaryotic genome maintenance.

PMID- 19101709
TI  - Early Acheulean technology in the Rietputs Formation, South Africa, dated with
      cosmogenic nuclides.
AB  - An absolute dating technique based on the build-up and decay of (26)Al and (10)Be
      in the mineral quartz provides crucial evidence regarding early Acheulean hominid
      distribution in South Africa. Cosmogenic nuclide burial dating of an ancient
      alluvial deposit of the Vaal River (Rietputs Formation) in the western interior
      of South Africa shows that coarse gravel and sand aggradation there occurred ca
      1.57+/-0.22Ma, with individual ages of samples ranging from 1.89+/-0.19 to 1.34+/
      0.22Ma. This was followed by aggradation of laminated and cross-bedded fine
      alluvium at ca 1.26+/-0.10Ma. The Rietputs Formation provides an ideal situation
      for the use of the cosmogenic nuclide burial dating method, as samples could be
      obtained from deep mining pits at depths ranging from 7 to 16 meters. Individual
      dates provide only a minimum age for the stone tool technology preserved within
      the deposits. Each assemblage represents a time averaged collection. Bifacial
      tools distributed throughout the coarse gravel and sand unit can be assigned to
      an early phase of the Acheulean. This is the first absolute radiometric dated
      evidence for early Acheulean artefacts in South Africa that have been found
      outside of the early hominid sites of the Gauteng Province. These absolute dates
      also indicate that handaxe-using hominids inhabited southern Africa as early as
      their counterparts in East Africa. The simultaneous appearance of the Acheulean
      in different parts of the continent implies relatively rapid technology
      development and the widespread use of large cutting tools in the African
      continent by ca 1.6Ma.

PMID- 19101710
TI  - Detailed chemical analysis of regional-scale air pollution in western Portugal
      using an adapted version of MCM v3.1.
AB  - A version of the Master Chemical Mechanism (MCM) v3.1, refined on the basis of
      recent chamber evaluations, has been incorporated into a Photochemical Trajectory
      Model (PTM) and applied to the simulation of boundary layer photochemistry in the
      Portuguese west coast region. Comparison of modelled concentrations of ozone and
      a number of other species (NO(x) and selected hydrocarbons and organic
      oxygenates) was carried out, using data from three connected sites on two case
      study days when well-defined sea breeze conditions were established. The ozone
      concentrations obtained through the application of the PTM are a good
      approximation to the measured values, the average difference being ca. 15%,
      indicating that the model was acceptable for evaluation of the details of the
      chemical processing. The detailed chemistry is examined, allowing conclusions to
      be drawn concerning chemical interferences in the measurements of NO(2), and in
      relation to the sensitivity of ozone formation to changes in ambient temperature.
      Three important, and comparable, contributions to the temperature sensitivity are
      identified and quantified, namely (i) an effect of increasing biogenic emissions
      with temperature; (ii) an effect of increasing ambient water vapour concentration
      with temperature, and its influence on radical production; and (iii) an increase
      in VOC oxidation chain lengths resulting from the temperature-dependence of the
      kinetic parameters, particularly in relation to the stability of PAN and its
      higher analogues. The sensitivity of the simulations to the refinements
      implemented into MCM v3.1 are also presented and discussed.

PMID- 19101712
TI  - Comparative hemostatic parameters in BALB/c, C57BL/6 and C3H/He mice.
AB  - This study describes micro-methods to determine biological parameters in plasma
      of three strains of mice. Platelet count was significantly different among
      strains. C57BL/6 mice showed the highest values (988 x 10(3)/microL) and BALB/c
      the lowest (782 x 10(3)/microL). Fibrinogen levels were 2.55 (C57BL/6), 2.37
      (BALB/c) and 2.28 g/L (C3H/He). Some inter-strain differences were observed in
      factor XIII (94, 118 and 114%) and plasminogen levels (142, 80 and 135%) in
      C57BL/6, BALB/c and C3H/He, respectively. Additionally, we observed individual
      mice factor XIII and plasminogen levels between 80 to 200% and 65 to 180%,
      respectively, in relation to pooled human plasma; and between 70 to 185% and 70
      to 155%, respectively, against pooled mice plasma. To our knowledge, this is
      first report in the literature in diverse mice strains regarding hemostasis,
      mainly on factor XIII, plasminogen levels, and a very simple test that allows
      measurement of endogenous fibrinolytic activity present in the plasma. The
      different results are discussed in relationship with existing literature
      regarding if the animals in some studies were maintained under strict pathogen
      free conditions, the collection of blood was from the heart or eye and if the
      analysis method was tested by counting manually or automatically. This work could
      contribute useful knowledge to the field of investigations regarding hemostatic
      disorders using mouse models, especially for laboratories that are not well
      equipped.

PMID- 19101713
TI  - Patients with a history of epithelial ovarian cancer presenting with a breast
      and/or axillary mass.
AB  - OBJECTIVE: A breast and/or axillary mass in a patient with epithelial ovarian
      cancer (EOC) may be due to an EOC breast metastasis or a second primary breast
      cancer. We sought to review our experience with patients with a history of EOC
      presenting with a breast and/or axillary mass to determine if clinical features
      differed between these entities. METHODS: Between 1/90 and 10/07, 29 women with
      epithelial EOC presented with a breast or axillary mass, including 10 patients
      with EOC metastatic to the breast and/or axilla and 19 patients with a second
      primary breast cancer following their original EOC diagnosis. Clinicopathologic
      factors/survival were retrospectively abstracted from medical records. RESULTS:
      The mean EOC disease-free survival (DFS) was 14.9 mo versus 77.4 mo (P<0.001) for
      patients with recurrent epithelial ovarian cancer metastatic to the breast and/or
      axilla and patients with a second primary breast cancer, respectively. Similarly,
      the mean interval between diagnosis of EOC and the breast and/or axillary event
      was 31.2 mo versus 70.7 mo for those patients who had metastatic recurrent EOC
      and those patients with breast cancer (P=0.02). Patients with a second primary
      breast cancer were more likely to be diagnosed on mammogram and have a family
      history of breast and ovarian carcinoma than patients with metastatic EOC to the
      breast and/or axilla (14/19 [73.7%] versus 2/9 [22.8%], P=0.02; and 12/18 [66.7%]
      versus 2/10 [20%], P=0.05, respectively). Median overall survival for patients
      with EOC metastasis was 26 mo but was not yet reached for those patients with a
      second primary breast cancer. On univariate analysis, an ovarian cancer DFS of 12
      mo or more and the performance of breast/axillary surgery were associated with a
      significantly longer overall survival (P=0.01 and 0.02, respectively), whereas an
      elevated CA125 level at the time of the breast/axilla event and the presence of
      EOC metastases to the breast and axilla were significant negative predictors of
      survival (P=0.01 and 0.05, respectively). CONCLUSION: The interval between EOC
      diagnosis and the breast and/or axilla event, an elevated CA125 level, and a
      family history of breast and/or ovarian cancer may help differentiate patients
      with metastatic EOC to the breast and/or axilla from those patients with a second
      primary breast cancer. The presence of a metastatic EOC portends a poor
      prognosis.

PMID- 19101711
TI  - Thrombophilia testing in patients with venous thromboembolism. Findings from the
      RIETE registry.
AB  - BACKGROUND: There is scarce information on the management habits with regard to
      thrombophilia testing in patients with venous thromboembolism (VTE). PATIENTS AND
      METHODS: RIETE is an ongoing registry of consecutive patients with symptomatic
      VTE. Aimed to estimate the extent to which thrombophilia test ordering patterns
      are consistent with the recommendations by a 2005 international consensus
      statement, we retrospectively compared the clinical characteristics of all
      patients tested for thrombophilia and those who were not tested. RESULTS: Of
      21367 patients enrolled, 4494 (21%) were tested for thrombophilia: 1456 (32%)
      tested positive, 3038 (68%) negative. The most common abnormalities were: Factor
      V Leiden (N=376), antiphospholipid syndrome (N=289), and prothrombin G20210A
      (N=263). Overall, 12740 (60%) patients met one or more criteria of the consensus
      statement: 7894 (37%) had a first episode of idiopathic VTE; 4013 (19%) were aged
      <50 years; 133 (0.6%) were pregnant women; 758 (3.5%) were using estrogens; 3375
      (16%) had recurrent VTE. Of them, 3618 (28%) underwent thrombophilia tests, 34%
      of whom tested positive. The percentage of patients testing positive was
      significantly higher in those aged <50 years, with no differences between
      idiopathic or secondary, first episode or recurrent VTE. Finally, 876 (10%) of
      the 8627 (40%) patients meeting no criteria were tested. Of these, 208 (24%)
      tested positive. CONCLUSIONS: Twenty-eight percent of patients meeting one or
      more criteria for thrombophilia testing, and 10% of those with no criteria were
      actually tested. Thus, a substantial proportion of thrombophilia ordering is not
      consistent with the recommendations made by the consensus statement.

PMID- 19101714
TI  - Serum paraoxonase and arylesterase activities in patients with epithelial ovarian
      cancer.
AB  - OBJECTIVE: The HDL-associated paraoxonase and arylesterase activities play a role
      in decreasing oxidative stress, which is known to contribute to cancer
      development. The aim of this study was to evaluate serum paraoxonase and
      arylesterase activities and lipid hydroperoxide (LOOH) levels in patients with
      newly-diagnosed epithelial ovarian cancer. MATERIALS: Serum paraoxonase and
      arylesterase activities, total free sulfhydryl (-SH) levels and LOOH levels were
      measured in patients with epithelial ovarian cancer (n=24) and controls (n=29).
      RESULTS: Serum paraoxonase activity and arylesterase activity, as well as -SH
      levels were significantly lower (p=0.003, p<0.001 and p<0.001, respectively) in
      patients with epithelial ovarian cancer compared to controls, while LOOH levels
      were significantly higher (p<0.001). A significant inverse correlation was found
      between the stage, grade and CA-125 level of ovarian cancer and paraoxonase
      activity (rho=-0.630, p=0.001 and rho=-0.601, p=0.002 and rho=-0.436, p=0.033,
      respectively), arylesterase activity (rho=-0.601, p=0.002 and rho=-0.713, p<0.001
      and rho=-0.580, p=0.003, respectively), and -SH levels (rho=-0.642, p=0.001 and
      rho=-0.637, p=0.001 and rho=-0.530, p=0.008, respectively). In contrast, there
      was a positive correlation between LOOH and the stage, grade and CA-125 level of
      ovarian cancer (rho=0.565, p=0.004 and rho=0.479, p=0.018 and rho=0.642,
      p=0.001). CONCLUSION: Our results suggest that diminished paraoxonase and
      arylesterase activity, -SH levels and increased LOOH levels are associated with
      particular stage, grade and CA-125 level of ovarian cancer.

PMID- 19101716
TI  - Nanoleakage, ultramorphological characteristics, and microtensile bond strengths
      of a new low-shrinkage composite to dentin after artificial aging.
AB  - OBJECTIVES: To study the microtensile bond strengths and nanoleakage of low
      shrinkage composite to dentin. The null hypotheses tested were (1) aging does not
      affect the bonding of low-shrinkage composite; (2) there is no difference in
      microtensile bond strengths and nanoleakage using different bonding strategies.
      METHODS: 32 extracted molars were assigned to one of four groups: LS System
      Adhesive (LS, 3M ESPE); dentin etched for 15s with phosphoric acid+LS System
      Adhesive (LSpa); Adper Single Bond Plus (SB, 3M ESPE); SB+LS Bond (SBLS).
      Occlusal dentin was exposed and restored with Filtek LS (3M ESPE). The samples
      were tested after 24h or after 20,000 thermocycles and 6 months of aging. Teeth
      were sectioned with a cross-section of 0.8+/-0.2mm(2) and fractured at a
      crosshead speed of 1mm/min. The data were submitted to ANOVA/Duncan's post hoc
      test, at p<0.05. Five slabs from each group were selected and immersed in 50wt%
      ammoniacal silver nitrate. Then, specimens were processed for SEM, the silver
      penetration was measured and data analyzed with Kruskal-Wallis at p<0.05.
      RESULTS: No statistically significant difference was found among the experimental
      groups for the factor dentin treatment (p=0.165) and aging (p=0.091). All
      experimental groups exhibit some degree of nanoleakage. There was no adhesion of
      Filtek LS applied directly over dentin surfaces treated with SB. SIGNIFICANCE:
      The new low-shrinkage resin composite showed compatibility only with its
      dedicated adhesive. Pre-etching did not improve the bond strengths to low
      shrinkage resin composite. Some degree of nanoleakage was evident in all groups.

PMID- 19101717
TI  - Sexual assault and MDMA: the distinction between consciousness and awareness when
      it comes to consent.
AB  - In France, the term chemical or drug-assisted submission is usually defined as
      the rendering of a person vulnerable by the surreptitious administration of an
      active substance with the purpose of prejudicing the person or his/her
      possessions. If the harm is sexual assault, establishing the victim's submission
      involves both proving that a dangerous substance was administered, providing
      material evidence of the infraction (the assault), i.e. the detection of traces
      in a physical examination and samples, and proving the absence of consent. We
      report the case of a woman who was sexually assaulted after having been
      surreptitiously administered methylenedioxymethamphetamine. In this special case,
      the woman remained in a state of vigilance (conscious) throughout, so there is
      doubt about whether or not she consented. In other words, the ability to consent
      is debatable.

PMID- 19101719
TI  - Tracing and ablation of single cells in the mammalian blastocyst using
      fluorescent DNA staining and multi-photon laser microscopy.
AB  - Comparing the vital DNA dyes Hoechst33342 and DAPI in their ability to visualise
      cell nuclei of the late rabbit blastocyst, both dyes were found to be equally
      suited despite differences in staining intensity in embryonic versus
      extraembryonic tissues and in nuclear versus cytoplasmic domains at the
      subcellular level: Both dyes stain all nuclei of a given cell layer (e.g.
      epiblast or hypoblast) evenly and provide satisfactory fluorescence contrast
      throughout the blastocyst, while not interfering with normal development up to 10
      h in vitro. Using short period (60-300 min) irradiation experiments with either
      dye, single-photon (405 nm) and multi-photon (800 nm) laser excitation was
      compared in different areas of the same embryo and parameters of multi-photon
      microscopy were defined for gentle live imaging and tracing of single cells deep
      to the surface of the embryo. In addition, individual cells were ablated by
      reducing the "area of interest" to sub-nucleus-size, thus maximally increasing
      the density of laser energy brought into the tissue. Thickening of epiblast and
      hypoblast and increased numbers of dense cytoplasmic inclusions within the limits
      of irradiated areas were found in semithin histological sections in a dose
      dependent manner. Ablated cells were found in a necrotic state while neighbouring
      cells remained apparently unscathed.

PMID- 19101718
TI  - The evaluation of the treatment response in obstructive meibomian gland disease
      by in vivo laser confocal microscopy.
AB  - PURPOSE: To evaluate the status of periglandular inflammation, ocular surface and
      tear function alterations in patients with obstructive meibomian gland disease
      (OMGD) by in vivo confocal microscopy before and after anti-inflammatory
      treatment, and to compare the results with patients receiving only topical non
      preserved artificial tears and sodium hyaluronate eye drops without anti
      inflammatory agents. METHODS: Thirty-two eyes of 16 OMGD patients receiving anti
      inflammatory treatment (treatment group) and 22 eyes of 11 OMGD patients
      receiving only topical non-preserved artificial tears and sodium hyaluronate eye
      drops (control group) were recruited in this prospective study. All subjects
      underwent slit-lamp examinations, tear film break-up time (BUT) measurements,
      fluorescein and Rose-Bengal stainings, Schirmer test capital I, Ukrainian without
      anesthesia, transillumination of the lids (meibography), and in vivo laser
      confocal microscopy of the lids (HRTII-RCM). RESULTS: The mean BUT, fluorescein
      staining scores, and inflammatory cell densities observed by in vivo confocal
      microscopy improved significantly in the group receiving anti-inflammatory
      treatment (p < 0.05), whereas no significant alterations of these parameters were
      observed in the group not receiving anti-inflammatory agents (p > 0.05).
      CONCLUSIONS: In vivo confocal microscopy was able to effectively demonstrate the
      treatment responses in patients with OMGD. Inflammatory cell density calculation
      seems to be a promising new parameter of in vivo confocal microscopy in the
      evaluation of treatment responses.

PMID- 19101720
TI  - Changes in heart rate recovery after high-intensity training in well-trained
      cyclists.
AB  - Heart rate recovery (HRR) after submaximal exercise improves after training.
      However, it is unknown if this also occurs in already well-trained cyclists.
      Therefore, 14 well-trained cyclists (VO(2max) 60.3 +/- 7.2 ml kg(-1) min(-1);
      relative peak power output 5.2 +/- 0.6 W kg(-1)) participated in a high-intensity
      training programme (eight sessions in 4 weeks). Before and after high-intensity
      training, performance was assessed with a peak power output test including
      respiratory gas analysis (VO(2max)) and a 40-km time trial. HRR was measured
      after every high-intensity training session and 40-km time trial. After the
      training period peak power output, expressed as W kg(-1), improved by 4.7% (P =
      0.000010) and 40-km time trial improved by 2.2% (P = 0.000007), whereas there was
      no change in VO(2max) (P = 0.066571). Both HRR after the high intensity training
      sessions (7 +/- 6 beats; P = 0.001302) and HRR after the 40-km time trials (6 +/-
      3 beats; P = 0.023101) improved significantly after the training period. Good
      relationships were found between improvements in HRR(40-km) and improvements in
      peak power output (r = 0.73; P < 0.0001) and 40-km time trial time (r = 0.96; P <
      0.0001). In conclusion, HRR is a sensitive marker which tracks changes in
      training status in already well-trained cyclists and has the potential to have an
      important role in monitoring and prescribing training.

PMID- 19101722
TI  - Fixation of the round ligament to the peritoneum and wrapping of the cut surface
      of the liver for prevention of early delayed gastric emptying after hepatic
      lateral segmentectomy.
AB  - PURPOSE: Left-sided hepatectomy occasionally leads to early delayed gastric
      emptying (EDGE). We developed a new fixation procedure of the round ligament to
      the peritoneum to prevent EDGE after hepatic lateral segmentectomy and evaluated
      its efficacy. METHODS: We retrospectively studied 42 patients who underwent
      hepatic lateral segmentectomy. They were divided into two groups: a fixation
      group (N = 15) and a nonfixation group (N = 27). The round ligament of the liver
      was divided at the umbilicus and detached from the abdominal wall from the
      umbilicus to the liver. The cut surface of the liver was wrapped by the round
      ligament, and the distal part of the round ligament was then fixated to the
      peritoneum. RESULTS: EDGE was found to be 0% in the fixation group versus 15% in
      the nonfixation group. CONCLUSIONS: Fixation of the round ligament to the
      peritoneum is a useful technique to prevent EDGE after hepatic lateral
      segmentectomy.

PMID- 19101723
TI  - Staged lavage versus single high-volume lavage in the treatment of
      feculent/purulent peritonitis: a matched pair analysis.
AB  - BACKGROUND: Spontaneous and iatrogenic secondary peritonitis remain to have a
      mortality of 10-30% and significant socioeconomic impact in survivors and
      especially non-survivors. Data on the most cost-effective treatment are lacking.
      We therefore studied outcome and resource utilization in a homogeneous cohort of
      patients with secondary fecal or purulent peritonitis undergoing surgery with
      source control and two different types of abdominal lavage. METHODS: Thirty-one
      consecutive patients with secondary feculent or purulent peritonitis of the lower
      gastrointestinal tract underwent a single high-volume lavage. That cohort was
      matched with 31 patients with the same source, extent, and quality of peritonitis
      treated by source control and staged lavage (intermittent lavage). RESULTS:
      Patients in both groups were comparable in gender distribution, age, comorbidity,
      source, extent, and severity of peritonitis with the history of intestinal
      perforation in the single high-volume lavage group being significantly higher
      than in the intermittent lavage group (2.0 +/- 1.7 vs. 1.1 +/- 0.8d; p = 0.008).
      Patients in the single high-volume lavage group had significantly less
      operations, thus requiring significantly less operation time (OR-time), intensive
      care unit (ICU)-requirement, ventilatory support, and inotropic support.
      CONCLUSION: Patients with secondary fecal or purulent peritonitis in at least two
      quadrants, undergoing a one step surgical repair including source control,
      primary anastomosis, and single high-volume lavage with more than 25 l have a
      comparable outcome to patients treated by staged lavage at significantly lower OR
      and ICU-utilization.

PMID- 19101724
TI  - Adaptation to a direction-dependent visuomotor gain in the young and elderly.
AB  - Consistent with the widely accepted notion of separate specification of movement
      amplitude and direction, it has been argued that there is also a categorical
      difference between adaptation to novel visuomotor rotations and to novel
      visuomotor gains. In line with this view, ageing seems to affect rotation and
      gain adaptation differently in that age-related impairments are consistently
      found for the former, but not for the latter. In this study we ask whether the
      contrasting findings could also be ascribed to differences in the level of
      difficulty of gain and rotation adaptation tasks, respectively. In order to
      increase the difficulty of gain adaptation, younger and older participants had to
      adapt to a direction-dependent gain transformation. Results revealed direction
      dependent adaptation in both groups. More importantly, we replicated the typical
      findings of age-related impairments of adaptation, but not of aftereffects, that
      were previously only reported for rotation adaptation. Younger participants also
      showed superior explicit knowledge regarding the novel visuomotor mapping as
      compared to the older participants. We show that this knowledge was used by
      younger participants to selectively augment adaptive shifts. Finally, our
      findings suggest that the difficulty of the novel visuomotor transformation and,
      related to this, the involvement of explicit knowledge in adaptation is critical
      for age-related changes to show up, but not the type of adaptation task, rotation
      and gain adaptation, respectively.

PMID- 19101725
TI  - Prevalence of Helicobacter pylori infection, chronic gastritis, and intestinal
      metaplasia in Mozambican dyspeptic patients.
AB  - We estimated the prevalence of Helicobacter pylori infection, chronic gastritis,
      atrophy, and intestinal metaplasia in dyspeptic patients from Maputo Central
      Hospital, Mozambique and evaluated the relationship between infection and
      histopathological features of chronic gastritis. Biopsies from 109 consecutive
      patients observed in 2005-2006 were collected from antrum, incisura angularis,
      and corpus for histopathological study according to the Modified Sydney system.
      H. pylori infection was assessed by histology and polymerase chain reaction. H.
      pylori prevalence was 94.5%. Chronic gastritis was the most frequent diagnosis
      (90.8%). Degenerative surface epithelial damage was associated with higher H.
      pylori density. Glandular atrophy (8.3%) and intestinal metaplasia (8.3%) were
      infrequent. Our results confirm previous observations in African countries with
      high prevalence of H. pylori infection and low rates of gastric cancer: high
      frequency of chronic H. pylori-associated gastritis with very low frequency of
      gastric atrophy and intestinal metaplasia.

PMID- 19101726
TI  - One-step nucleic acid amplification-a molecular method for the detection of lymph
      node metastases in breast cancer patients; results of the German study group.
AB  - Sentinel lymph node (SN) biopsy is part of the staging procedure in breast cancer
      patients. In this study, we compared an intraoperative tool named one-step
      nucleic acid amplification (OSNA) to our routine histological investigation. OSNA
      consists of a short homogenization step followed by amplification of cytokeratin
      (CK) 19 mRNA directly from the lysate. To evaluate the performance of OSNA in
      comparison to histology, analysis of 343 axillary lymph nodes (ALN) from 93
      breast cancer patients was performed with both methods. Discordant samples were
      subjected to other methods. If these tests supported the OSNA results, these
      samples were excluded from the study. The concordance rate was 91.8%, sensitivity
      98.1%, and specificity 90.8% before and 95.5%, 100%, and 95.6%, respectively,
      after discordant case investigation. Our results show that OSNA is an excellent
      method for the detection of metastases in lymph nodes and can be applied as an
      intraoperative diagnostic approach.

PMID- 19101727
TI  - Clinicopathological features and prognosis of Chinese children with idiopathic
      nephrotic syndrome between different age groups.
AB  - Ethnicity and age play important roles in the epidemiology of idiopathic
      nephrotic syndrome (INS) in children. The purposes of this study were to compare
      the clinical features, renal histopathology, steroid response, and long-term
      prognosis in Chinese children between different age groups. This is a
      retrospective cohort study of children aged between 2 and 18 years old with INS.
      Patients were divided into two groups according to age. Group I consisted of
      children between 2 and 8 years old (n = 49). Group II consisted of the remaining
      patients (n = 50). The clinical biochemical parameters, response to steroid
      treatment, renal histology, and long-term outcomes were analyzed. The biochemical
      parameters at the onset were similar in the two groups. Group II had a
      significantly higher frequency of microscopic hematuria (P = 0.011). Of the 67
      children biopsied, minimal change disease was the most common histopathology for
      both groups. There was a higher frequency with focal and segmental
      glomerulosclerosis in group II (24% vs. 6.1%), but the difference between the two
      groups was not significant. During follow-up, the frequency of hypertension was
      significantly higher in group II (P = 0.006). Two cases in group I developed
      chronic kidney disease (CKD) vs. eight cases in group II. The frequency of
      progression to CKD is significantly higher (P = 0.042) in Group II. In
      conclusion, children beyond 8 years of age with INS have a higher incidence of
      microscopic hematuria, higher risk of hypertension and progression to CKD in long
      term follow-up.

PMID- 19101728
TI  - Tumor with watery diarrhoea, hypokalaemia in a 3-year-old girl.
AB  - Watery diarrhoea, hypokalaemia and achlorhydria (WDHA) syndrome was caused by
      vasoactive intestinal polypeptide (VIP)-producing tumour. A 3-year-old Chinese
      girl with watery diarrhoea, abdominal distension and hypokalaemia due to a
      thoracic paraspinal VIP-secreting ganglioneuroma is reported. The girl coughed,
      fevering up to 39 degrees C after a flu-like episode. She had eight to ten
      abundant stools daily which is not improved by dietary treatment, resulting in an
      important weight loss. She weighed 6.8 kg (nl P50 at 6 months of age) and is 76
      cm (nl P50 at 9 months of age) in height. Blood electrolytes showed 129 mmol/L
      sodium, 2.42 mmol/L potassium, 94 mmol/L chloride and 18.6 mmol/L bicarbonate;
      urinary catecholamines were normal. Computed tomography scan evidenced a left
      side paravertebral mass of 4 x 6 cm in the lower thoracic region leading to the
      blood determination of vasoactive intestinal polypeptide which amounted 830
      pmol/L(normal < 25 pmol/L). Surgical removal showed a ganglioneuroma of 160 g and
      was associated with disappearance of the diarrhoea and normalization of VIP level
      below 20 pmol/L. Review of the 63 reported cases in children with WDHA showed
      that many of the cases presented with non-treatable watery diarrhoea,
      hypokalaemia. Achlorhydria is not necessarily part of the WDHA syndrome. The male
      to female ratio is 1:1.5. Ganglioneuroblastoma and ganglioneuroma are the
      commonest tumours. Location of the tumour is variable: abdomen, chest or neck.
      Abdominal distension, flushing, episodic hypertension and colonic dilatation,
      constipation and ataxia were the other associated features. Surgical resection is
      the treatment of choice of VIP-producing tumours.

PMID- 19101729
TI  - QT interval prolongation and risk for cardiac events in genotyped LQTS-index
      children.
AB  - Congenital long-QT syndrome (LQTS) is an inherited cardiac disorder with a
      disturbance in repolarization characterized by a prolonged QT interval on the
      surface electrocardiogram and life-threatening ventricular tachycardia.
      Publications from the International LQTS Registry have provided information that
      the cardiac risk may be influenced by gender, genotype, exposure to arrhythmia
      triggers, and previous cardiac events. In children, early-onset of disease,
      changes in life style, and medical treatment is a sensitive issue and
      significant, gender-related differences of a first life-threatening event were
      reported. Thus, we investigated the clinical features of a large genotyped
      population of LQTS-index children (age < or =16 years) upon a single-center
      experience and determined risk factors for symptoms. Of 83 children [mean
      corrected QT interval (QTc) 510 +/- 74 ms], 89% had LQT1, -2, or -3. Nine
      patients (11%) were identified as having Jervell and Lange-Nielsen syndrome.
      Among symptomatic children (n = 51, 61%), syncope was the most prevalent symptom
      at initial presentation (49%); however, aborted cardiac arrest (ACA) occurred in
      33% and sudden cardiac death (SCD) in 18%, respectively, as the initial
      manifestation. During a mean follow-up period of 5.9 +/- 4.7 years, 31% of the
      children developed symptoms while on therapy (86% syncope, 9% ACA, 5% SCD).
      Statistical analyses of risk factors for cardiac events showed that the QTc >500
      ms was a strong and significant predictor for cardiac events during follow-up (p
      = 0.02). Furthermore, a prior syncope [hazard ratio (HR), 4.05; 95% confidence
      interval (CI), 1.1 to 15.0; p = 0.03] or an ACA (HR, 11.7; 95% CI, 3.1 to 43.4; p
      = <0.001) identified children with an increased risk for recurrent cardiac events
      compared to asymptomatic LQT children. LQTS-index children manifest with a high
      percentage of severe symptoms. Among presently validated risk factors for LQTS, a
      QTc interval >500 ms and a history of prior syncope or ACA were strong predictors
      for recurrent cardiac events.

PMID- 19101730
TI  - Down-regulation of plasma membranous Annexin A1 protein expression in
      premalignant and malignant lesions of the oral cavity: correlation with
      epithelial differentiation.
AB  - PURPOSE: To determine the potential involvement of ANXA1 in oral squamous-cell
      carcinoma (OSCC), we evaluated the ANXA1 protein expression in oral premalignant
      lesions (OPLs) and OSCCs and correlated the results with clinicopathologic
      variables. METHODS: Matched normal and tumour specimens of 44 primary OSCCs and
      28 OPLs were analyzed for ANXA1 subcellular localization and protein expression
      level by immunohistochemistry (IHC). Correlations between ANXA1-IHC staining
      scores of OSCCs and clinicopathologic features were evaluated by Fisher's exact
      test. RESULTS: Markedly down-regulation of ANXA1 protein expression was
      identified on the plasma membrane of epithelial cells in OSCCs (P < 0.001) and
      OPLs (P = 0.001) compared with normal counterparts. Moreover, loss of plasma
      membranous ANXA1 expression was significantly correlated with the poorly
      differentiated status of OSCC cells (P = 0.012). CONCLUSIONS: Our findings
      suggest that loss of ANXA1 is frequent and early event during oral carcinogenesis
      and that ANXA1 could contribute to maintaining epithelial differentiation in
      OSCC.

PMID- 19101731
TI  - Differentiation between neurofibromas and malignant peripheral nerve sheath
      tumors in neurofibromatosis 1 evaluated by MRI.
AB  - PURPOSE: The imaging discrimination between neurofibroma (NF) and malignant
      peripheral nerve sheath tumor (MPNST) is clinically very important. The purpose
      of this study is to define the criteria for the differential diagnosis between NF
      and MPNST on MRI in neurofibromatosis 1 (NF1). METHODS: A total of 37 patients
      with NF1, 18 NFs and 19 MPNSTs were evaluated by MRI at 1.5 T. Magnetic resonance
      imaging (MRI) findings were compared using univariate and multivariate analyses.
      RESULTS: The MRI findings characteristic of MPNST (p < 0.05) were an irregular
      tumor shape (15/19 in MPNST vs. 5/18 in NF), unclear margin (13/19 in MPNST vs.
      6/18 in NF), intra-tumoral lobulation (12/19 in MPNST vs. 3/18 in NF), presence
      of high signal-intensity area on T1-weighted images (T1WI) (12/19 in MPNST vs.
      1/18 in NF), no target sign (0/19 in MPNST vs. 12/18 in NF), inhomogeneous
      enhancement on contract-enhanced T1WI (17/18 in MPNST vs. 9/16 in NF) and a lower
      rate of enhanced area (54% in MPNST vs. 87% in NF) were critical indicators to
      differentiate MPNST from NF. A multivariate analysis showed that intra-tumoral
      lobulation and the presence of a high signal-intensity area on T1WI were
      considered to be diagnostic indicators of MPNST. The sensitivity and specificity
      for these two items were 63.2, 83.3, 63.2 and 87.5%, respectively. CONCLUSION:
      MRI shows features which were helpful for differentiating MPNST from NF.

PMID- 19101732
TI  - Partial sequence of the beta-tubulin of Histomonas meleagridis and the activity
      of benzimidazoles against H. meleagridis in vitro.
AB  - The protozoan parasite Histomonas meleagridis is a member of the family
      Monocercomonadidae in the class Trichomonada. Due to food safety concerns,
      currently no prophylactic or therapeutic drug against the parasite is licensed in
      the European Union. Benzimidazoles are antiparasitic drugs, and some of them are
      licensed for use in food-producing animals. Benzimidazoles act on beta-tubulin,
      and the beta-tubulin sequence allows predictions about the efficacy of
      benzimidazoles. In this study, we sequenced and analyzed a part of the beta
      tubulin gene of five H. meleagridis strains and of Dientamoeba fragilis. In each
      Histomonas strain, three to five different sequences were found. No clustering of
      sequences from the same strain was recognizable. A phylogenetic tree based on the
      amino acid sequences of trichomonal beta-tubulin genes placed the histomonal
      sequences on a branch with D. fragilis, separate from Monocercomonas sp. and
      Tritrichomonas foetus. All histomonal amino acid sequences predicted a
      susceptibility to benzimidazoles. However, when we tested the efficacy of five
      benzimidazoles, namely, albendazole, fenbendazole, flubendazole, mebendazole, and
      nocodazole, on H. meleagridis in vitro, all tested drugs showed no efficacy, even
      though the concentrations tested were higher than the concentrations found to be
      effective against Trichomonas vaginalis and T. foetus by other investigators.

PMID- 19101733
TI  - Global richness patterns of venomous snakes reveal contrasting influences of
      ecology and history in two different clades.
AB  - Recent studies addressing broad-scale species richness gradients have proposed
      two main primary drivers: contemporary climate and evolutionary processes
      (differential balance between speciation and extinction). Here, we analyze the
      global richness patterns of two venomous snake clades, Viperidae and Elapidae. We
      used ordinary least squares multiple regression (OLS) and partial regression
      analysis to investigate to what extent actual evapotranspiration (AET;
      summarizing current environmental conditions) and biogeographical regions
      (representing evolutionary effects) were associated with species richness. For
      viperids, AET explained 45.6% of the variance in richness whereas the effect of
      this variable for elapids was almost null (0.5%). On the other hand,
      biogeographic regions were the best predictors of elapid richness (56.5%),
      against its relatively small effect (25.9%) in viperid richness. Partial
      regressions also revealed similar patterns for independent effects of climate and
      history in both clades. However, the independent historical effect in Elapidae
      decreased from 45.2 to 17.8% when we excluded Australia from the analyses,
      indicating that the strong historical effect that had emerged for the global
      richness pattern was reflecting the historical process of elapid radiation into
      Australia. Even after excluding Australia, the historical signal in elapid
      richness in the rest of the globe was still significant and much higher than that
      observed in viperid richness at a global scale (2.7% after controlling for AET
      effects). Differences in the evolutionary age of these two clades can be invoked
      to explain these contrasting results, in that viperids probably had more time for
      diversification, generating richness responses to environmental gradients,
      whereas the pattern of distribution of elapid richness can be more directly
      interpreted in an evolutionary context. Moreover, these results show the
      importance of starting to adopt deconstructive approaches to species richness,
      since the driving factors of these patterns may vary from group to group
      according to their evolutionary history.

PMID- 19101734
TI  - Comparison of saccharification process by acid and microwave-assisted acid
      pretreated swine manure.
AB  - The saccharification process of swine manure by conventional and microwave
      assisted acid pretreated were investigated using cellulose enzymes, respectively.
      The optima for microwave-assisted acid pretreated swine manure is achieved when
      swine manure of 50 g l(-1) of substrate concentration and water amount 40 ml was
      pretreated by 4% H2SO4 concentration with 445 W microwave powers for 30 min at
      pretreatment period, and temperature 50 degrees C, enzyme loading 2 mg g(-1)
      substrate, substrate concentration 5 g l(-1) and initial medium pH 4.8 at enzymes
      hydrolysis period by microwave-assisted acid pretreated, respectively. The
      optimal conditions by conventional acid pretreated is obtained when 50 g l(-1)
      swine manure was submerged in 40 ml, 4% H2SO4 maintained at 130 degrees C for 3 h
      at pretreatment period, and temperature 45 degrees C, enzyme loading 2 mg g(-1)
      substrate, substrate concentration 15 g l(-1) and initial medium pH 5.2 at
      enzymes hydrolysis period, respectively. Under the optimum conditions microwave
      assisted acid pretreatment could achieve higher yield of reducing sugar, short
      reaction time, and lower energy consumption than from the conventional acid
      pretreatment, which indicates that microwave-assisted acid pretreatment is more
      suitable for swine manure pretreatment than by acid alone.

PMID- 19101735
TI  - Climate impact on suicide rates in Finland from 1971 to 2003.
AB  - Seasonal patterns of death from suicide are well-documented and have been
      attributed to climatic factors such as solar radiation and ambient temperature.
      However, studies on the impact of weather and climate on suicide are not
      consistent, and conflicting data have been reported. In this study, we performed
      a correlation analysis between nationwide suicide rates and weather variables in
      Finland during the period 1971-2003. The weather parameters studied were global
      solar radiation, temperature and precipitation, and a range of time spans from 1
      month to 1 year were used in order to elucidate the dose-response relationship,
      if any, between weather variables and suicide. Single and multiple linear
      regression models show weak associations using 1-month and 3-month time spans,
      but robust associations using a 12-month time span. Cumulative global solar
      radiation had the best explanatory power, while average temperature and
      cumulative precipitation had only a minor impact on suicide rates. Our results
      demonstrate that winters with low global radiation may increase the risk of
      suicide. The best correlation found was for the 5-month period from November to
      March; the inter-annual variability in the cumulative global radiation for that
      period explained 40 % of the variation in the male suicide rate and 14 % of the
      variation in the female suicide rate, both at a statistically significant level.
      Long-term variations in global radiation may also explain, in part, the observed
      increasing trend in the suicide rate until 1990 and the decreasing trend since
      then in Finland.

PMID- 19101736
TI  - Overwintering strategy of wild free-ranging and enclosure-housed Japanese raccoon
      dogs (Nyctereutes procyonoides albus).
AB  - The raccoon dog, Nyctereutes procyonoides, is a canid with a passive
      overwintering strategy in northern Europe. However, the behaviour and physiology
      of the Japanese subspecies, N. p. albus, which has fewer chromosomes than the
      other subspecies, remain unknown. We measured body temperature, body composition
      and blood biochemistry of wild free-ranging and fasted enclosure-housed N. p.
      albus during boreal winter in Hokkaido, Japan. Body temperature of N. p. albus
      decreased from 38 degrees C in autumn to 35.9-36.7 degrees C while maintaining a
      circadian rhythm in late February (n = 3). A transient 18-36% decrease in resting
      heart rate occurred when body temperature was low (n = 2). Despite a 33-45%
      decrease in body weight due to winter fasting, circulating glucose, total protein
      and triglyceride levels were maintained (n = 4). Serum urea nitrogen dropped by
      43-45% from autumn to spring, suggesting protein conservation during fasting. The
      overwintering survival strategy of N. p. albus in central Hokkaido is based upon
      large changes in seasonal activity patterns, winter denning and communal housing
      without the large decrease in body temperature that is characteristic of
      subarctic animals exhibiting hibernation or torpor.

PMID- 19101737
TI  - The arbuscular mycorrhizal symbiosis links N mineralization to plant demand.
AB  - Arbuscular mycorrhizal (AM) fungi facilitate inorganic N (NH(4)(+) or NO(3)(-))
      uptake by plants, but their role in N mobilization from organic sources is
      unclear. We hypothesized that arbuscular mycorrhizae enhance the ability of a
      plant to use organic residues (ORs) as a source of N. This was tested under
      controlled glasshouse conditions by burying a patch of OR in soil separated by 20
      microm nylon mesh so that only fungal hyphae can pass through it. The fate of the
      N contained in the OR patch, as influenced by Glomus claroideum, Glomus clarum,
      or Glomus intraradices over 24 weeks, was determined using (15)N as a tracer. AM
      fungal species enhanced N mineralization from OR to different levels. N recovery
      and translocation to Russian wild rye by hyphae reached 25% of mineralized N in
      G. clarum, which was most effective despite its smaller extraradical development
      in soil. Mobilization of N by G. clarum relieved plant N deficiency and enhanced
      plant growth. We show that AM hyphae modify soil functioning by linking plant
      growth to N mineralization from OR. AM species enhance N mineralization
      differentially leading to species-specific changes in the quality of the soil
      environment (soil C-to-N ratio) and structure of the soil microbial community.

PMID- 19101738
TI  - Comparison of platelet pellet with or without guided tissue regeneration in the
      treatment of class II furcation defects in dogs.
AB  - The purpose of this study was to compare histological effectiveness of platelet
      pellet (PP), which has higher platelet content than platelet-rich plasma, and the
      combination of PP/guided tissue regeneration (GTR) for class II furcation defects
      in dogs. The mandibular second, third, and fourth premolars of both sides in four
      dogs were used. Class II furcation defects (5 mm in height and 2 mm in depth)
      were surgically created. Five weeks after the first operation, second premolars
      were treated with scaling and root planing (group 1); right third and fourth
      premolars received PP (group 2), and left premolars received the combination of
      PP/GTR (group 3). Percentage of cementum and alveolar bone formation were
      evaluated by histometric analysis after a healing period of 12 weeks. There was
      new cementum along with periodontal ligament and coronal growth of alveolar bone
      in all groups. Cementum formation was significantly higher in groups 2 and 3
      compared to the control group (P < 0.05) with no significant difference between
      groups 2 and 3. Limited alveolar bone formation was statistically similar in all
      groups (P > 0.05). It is concluded that both PP and the combination of PP/GTR are
      effective in the treatment of class II furcation defects in dogs. PP thus appears
      to be a suitable alternative material in the regenerative periodontal therapy.

PMID- 19101739
TI  - Two years survival rate of class II composite resin restorations prepared by ART
      with and without a chemomechanical caries removal gel in primary molars.
AB  - The aim was to test the null hypotheses that there is no difference: (1) in
      carious lesion development at the restoration margin between class II composite
      resin restorations in primary molars produced through the atraumatic restorative
      treatment (ART) with and without a chemomechanical caries removal gel and (2) in
      the survival rate of class II composite resin restorations between two treatment
      groups after 2 years. Three hundred twenty-seven children with 568 class II
      cavitated lesions were included in a parallel mouth study design. Four operators
      placed resin composite (Filtek Z 250) restorations bonded with a self-etch
      adhesive (Adper prompt L pop). Two independent examiners evaluated the
      restorations after 0.5, 1, and 2 years using the modified Ryge criteria. The
      Kaplan-Meier survival method was applied to estimate survival percentages. A high
      proportion of restorations were lost during the study period. Therefore, the
      first hypothesis could not be tested. No statistically significant difference was
      observed between the cumulative survival percentages of restorations produced by
      the two treatment approaches over the 2-year period (ART, 54.1 +/- 3.4%; ART with
      Carisolv, 46.0 +/- 3.4%). This hypothesis was accepted. ART with chemomechanical
      gel might not provide an added benefit increasing the survival percentages of ART
      class II composite resin restorations in primary teeth.

PMID- 19101740
TI  - The role of Candida albicans hyphae and Lactobacillus in denture-related
      stomatitis.
AB  - Denture-related stomatitis (DRS) is still a dilemma in removable prosthodontics.
      The aim of this study was to investigate the relationship of DRS with the
      presence of Candida albicans hyphae and Lactobacillus. A total of 91 patients
      wearing maxillary and mandibular complete dentures were included in the present
      study and tested mycologically as well as bacteriologically. A statistically
      significant association of DRS was found with denture age (p = 0.003) and
      continuous denture wearing (p = 0.015). Presence of C. albicans hyphae was shown
      to be significantly higher in DRS cases (p < 0.01), and there was a statistically
      significant positive correlation between presence of hyphae and C. albicans (p <
      0.01). Another interesting finding was that DRS patients showed higher
      Lactobacillus counts in their saliva (p = 0.04), as well as in the palate (p =
      0.028). C. albicans is an important factor in the development of DRS. Hyphae seem
      to facilitate the rise of C. albicans counts and be related to the inflammatory
      response of the tissues. Lactobacillus seems to play an important role in the
      presence of DRS, as well. In agreement with many other studies, the results of
      this study confirm the importance of denture age and continuous denture wearing
      in the development of DRS.

PMID- 19101742
TI  - Relaxation times and energy barriers of rubbing-induced birefringence in glass
      forming polymers.
AB  - The relaxations of rubbing-induced birefringence (RIB) in several glass-forming
      polymers, including polycarbonate and polystyrene (PS) derivatives with various
      modifications to the phenyl ring side group, are studied. Significant relaxations
      of RIB are observed at temperatures well below the glass transition temperature T
      (g) . The relaxation times span a wide range from approximately 10 s to probably
      geological time scale. Physical aging effects are absent in the RIB relaxations.
      The model proposed for the interpretation of RIB in PS describes well the RIB
      relaxations in all the polymers investigated here. The energy barriers are of the
      order of a few hundred kJ/mol and decrease with decreasing temperature, in
      opposition to the trend of Vogel-Fulcher form for polymer segmental relaxations
      above T (g) . The relaxation behaviors of different polymers are qualitatively
      similar but somewhat different in quantitative details, such as in the values of
      the saturated birefringence, the shape of the initial barrier density
      distribution functions, the rates of barrier decrease with decreasing
      temperature, and the dependence of relaxation times on temperature and parameter
      xi , etc. The RIB relaxations are different from any of the other relaxations
      below T (g) that have been reported in the literature, such as dielectric
      relaxations or optical probe relaxations. A microscopic model for the relaxations
      of RIB is much desired.

PMID- 19101741
TI  - Diffusion in supported lipid bilayers: influence of substrate and preparation
      technique on the internal dynamics.
AB  - The diffusion law of DMPC and DPPC in Supported Lipid Bilayers (SLB), on
      different substrates, has been investigated in details by Fluorescence Recovery
      After Patterned Photobleaching (FRAPP). Over micrometer length scales, we
      demonstrate the validity of a purely Brownian diffusive law both in the gel and
      the fluid phases of the lipids. Measuring the diffusion coefficient as a function
      of temperature, we characterize the gel-to-liquid phase transition of DMPC and
      DPPC. It is shown that, depending on the type of substrate and the method used
      for bilayer preparation, completely different behaviours can be observed. On
      glass substrates, using the Langmuir-Blodgett deposition technique, both leaflets
      of the bilayer have the same dynamics. On mica, the dynamics of the proximal
      leaflet is slower than the dynamics of the distal leaflet, although the
      transition temperature is the same for both layers. Preparing bilayers from
      vesicle fusion in same conditions leads to more random behaviours and shifted
      transition temperatures.

PMID- 19101743
TI  - Cost-effectiveness of strong opioids focussing on the long-term effects of opioid
      related fractures: a model approach.
AB  - Opioid analgesics are known to impact on the central nervous system (CNS). These
      CNS side effects, such as dizziness and confusion, have been shown to lead to an
      increased risk of falling with subsequent fractures in elderly patients being
      treated with opioids. The risk of experiencing fractures has been shown to be
      dependent on the substance administered. Therefore, a health economic model was
      developed to investigate the cost-effectiveness of the most commonly used strong
      opioids in Germany, focussing on opioid-related fractures. By means of a Markov
      model, the consequences of hip, spine and forearm fractures due to the prior
      administration of transdermal (TD) buprenorphine, TD fentanyl, oral oxycodone as
      well as oral morphine were assessed from the perspectives of the German statutory
      health insurance (SHI) and the German social security (GSS) system over a time
      horizon of 6 years. The most frequently prescribed strength/package-size
      combinations of these opioids were taken into consideration, including generics
      where available. The results of the present analysis predict that TD
      buprenorphine is dominant compared to TD fentanyl and oxycodone by showing better
      effects [life years gained/quality adjusted life years (QALY) gained] at lower
      cost. From the SHI perspective, the incremental cost-effectiveness ratio (ICER)
      compared to morphine is <euro> 6,801.61 per life year gained, and <euro> 7,766.11
      per QALY gained. From the GSS perspective, the ICER is <euro> 2,496.77 per life
      year gained and <euro> 2,850.83 per QALY gained. The model is robust regarding
      probabilistic variations of all parameters in the sensitivity analyses. Focussing
      on fractures due to the prior administration of strong opioids, TD buprenorphine
      is less costly and more effective than TD fentanyl and oxycodone and represents a
      cost-effective treatment option versus morphine in patients with chronic pain
      from both the SHI and GSS perspective in Germany.

PMID- 19101744
TI  - Rod and S-cone driven ERG signals at high retinal illuminances.
AB  - The purpose of the present study was to investigate whether L- and M-cone driven
      responses can be influenced by concomitant modulation in the rods or the S-cones.
      In addition, it was studied whether a change in the state of adaptation in L- or
      M-cones can have a different influence on ERG data when simultaneously the mean
      number of photoisomerizations in either rods or S-cones is altered. It was found
      that rods and/or S-cones cannot be neglected when measuring L- or M-cone driven
      ERGs.

PMID- 19101745
TI  - Heavy metal contamination in the vicinity of an industrial area near Bucharest.
AB  - BACKGROUND, AIM, AND SCOPE: Heavy metals such as lead are well known to cause
      harmful health effects. Especially children are particularly susceptible to
      increased levels of lead in their blood. It is also a fact that lead
      concentration is increasing in the environment due to increased anthropogenic
      activity. The risk of heavy metal contamination is pronounced in the environment
      adjacent to large industrial complexes. In a combined case study, the
      environmental pollution by heavy metals was related to children's health in the
      vicinity of an industrial area located 4 km south-east from Bucharest about 2 km
      east from the nearest town-Pantelimon. This site includes companies processing
      different, nonferrous solid wastes for recovery of heavy metals and producing
      different nonferrous alloys and lead batteries. In this paper, mainly the results
      of environmental sampling and analyses are summarized. MATERIALS AND METHODS:
      Water, soil, and atmospheric deposition samples were collected from different
      locations within 3 km from the industrial area. For comparison, samples were also
      taken from Bucharest. Water samples were filtered (<0.45 microm), extracted by
      salpetric acid, and quantified by ICP-OES and ICP-MS. Soil samples were dried,
      sieved (<2 mm), extracted by aqua regia and analyzed by AAS. In order to quantify
      the atmospheric deposition, three kinds of permanently open collecting pots were
      used on nine different sites between August and November 2006. RESULTS: At most
      sampling locations, the heavy metal concentrations in soil decrease with
      increasing distance to the presumably major source of pollution. Highest heavy
      metal concentrations were found in 10-20 cm soil depths. There were also
      decreasing heavy metal concentrations for atmospheric deposition with increasing
      distance to the industrial site. In surface and groundwater samples, traces of
      zinc, copper and lead were detected. DISCUSSION: The heavy metal concentrations
      in soil were increased in the study area, mostly under legal action limits in low
      concern areas (e.g., 1,000 mg Pb/kg dry soil), but often above action limits for
      high-concern areas (100 mg Pb/kg dry soil) such as populated areas. The soluble
      lead concentrations in water samples indicate a need for monitoring and assessing
      water quality in more detail. The results for atmospheric deposition showed
      increased dust precipitation and heavy metal loads in the study area compared to
      Bucharest. However, based on mass flow balance calculations, the actual
      atmospheric deposition of heavy metals must be much lower than it was in the past
      decades. CONCLUSIONS: It was shown that highest lead values in water, soil and
      atmospheric deposition are rather to be found near the investigated industrial
      site than at the control sites in Bucharest. Our results correspond very well
      with results that show that children from Pantelimon have significantly increased
      lead concentrations in their blood compared to children in Bucharest. The
      increased lead contamination around the investigated industrial area is likely to
      have caused the increased exposure for children living in Pantelimon.
      RECOMMENDATIONS AND PERSPECTIVES: In high-concern areas, such as found in
      populated areas, further measures have to be taken to avoid health risks for
      people living in these areas. The measures already taken to reduce emissions from
      the industrial site will help to avoid further increases in heavy metal
      concentrations. In areas with exceeded action limits, measures have to be taken
      as required by law. Detailed risk assessments could help to take necessary
      actions to protect public health in this area. The public should be informed
      about the potential hazards of eating plants grown in that area. Educational
      programs for schools, informing children about the contamination, should lead to
      a better understanding of environmental problems and a more sustainable behavior
      in the future.

PMID- 19101746
TI  - Longevity of orders is related to the longevity of their constituent genera
      rather than genus richness.
AB  - Longevity of a taxonomic group is an important issue in understanding the
      dynamics of evolution. In this respect a key observation is that genera, families
      or orders can each be assigned a characteristic average lifetime (Van Valen in
      Evol Theory 1:1-30, 1973). Using the fossil marine animal genera database
      (Sepkoski in Bull Am Paleontol 363, pp 563, 2002) we here examine the
      relationship between longevity of a higher taxonomic group (orders) and the
      longevity of its lower taxonomic groups (genera). We find insignificant
      correlation between the size of an order and its longevity, whereas we observe
      large correlation between the lifetime of an order and the lifetime of its
      constituent genera. These observations suggest that longevity of taxonomic groups
      is heritable intrinsically or on the grounds of environmental preferences.

PMID- 19101747
TI  - Tribute to Wolfgang Schaper on the occasion of his 75th birthday.

PMID- 19101748
TI  - On the occasion of Wolfgang Schaper's 75th birthday.

PMID- 19101750
TI  - Thyroid hormone improves postischaemic recovery of function while limiting
      apoptosis: a new therapeutic approach to support hemodynamics in the setting of
      ischaemia-reperfusion?
AB  - Although it has long been recognized that thyroid hormone is an effective
      positive inotrope, its efficacy in supporting hemodynamics in the acute setting
      of ischaemia and reperfusion (R) without worsening reperfusion injury remains
      largely unknown. Thus, we investigated the effects of triiodothyronine (T3) on
      reperfusion injury in a Langendorff-perfused rat heart model of 30 min zero-flow
      ischaemia and 60 min of (R) with or without T3 (40 microg/l) at R, T3-R60, n = 11
      and CNT-R60, n = 10, respectively. Furthermore, phosphorylated levels of
      intracellular kinases were measured at 5, 15 and 60 min of R. T3 markedly
      improved postischaemic recovery of left ventricular developed pressure (LVDP%);
      56.0% (SEM, 4.4) in T3-R60 versus 38.8% (3.1) in CNT-R60, P < 0.05. Furthermore,
      LDH release was significantly lower in T3-R60. Apoptosis detection by fluorescent
      probe optical imaging showed increased fluorescent signal in CNT-R60 hearts,
      while the signal was hardly detectable in T3-R60 hearts. Similarly, caspase-3
      activity was found to be 78.2 (8.2) in CNT-R60 vs 40.5 (7.1) in T3-R60 hearts, P
      < 0.05. This response was associated with significantly lower levels of phospho
      p38 MAPK at any time point of R. No significant changes in phospho- ERK1/2 and
      JNK levels were observed between groups. Phospho-Akt levels were significantly
      lower in T3 treated group at 5 min and no change in phospho-Akt levels were
      observed at 15 and 60 min between groups. In conclusion, T3 administration at
      reperfusion can improve postischaemic recovery of function while limiting
      apoptosis. This may constitute a paradigm of a positive inotropic agent with anti
      apoptotic action suitable for supporting hemodynamics in the clinical setting of
      ischaemia-reperfusion.

PMID- 19101749
TI  - Collateral circulation: past and present.
AB  - Following an arterial occlusion outward remodeling of pre-existent inter
      connecting arterioles occurs by proliferation of vascular smooth muscle and
      endothelial cells. This is initiated by deformation of the endothelial cells
      through increased pulsatile fluid shear stress (FSS) caused by the steep pressure
      gradient between the high pre-occlusive and the very low post-occlusive pressure
      regions that are interconnected by collateral vessels. Shear stress leads to the
      activation and expression of all NOS isoforms and NO production, followed by
      endothelial VEGF secretion, which induces MCP-1 synthesis in endothelium and in
      the smooth muscle of the media. This leads to attraction and activation of
      monocytes and T-cells into the adventitial space (peripheral collateral vessels)
      or attachment of these cells to the endothelium (coronary collaterals).
      Mononuclear cells produce proteases and growth factors to digest the extra
      cellular scaffold and allow motility and provide space for the new cells. They
      also produce NO from iNOS, which is essential for arteriogenesis. The bulk of new
      tissue production is carried by the smooth muscles of the media, which transform
      their phenotype from a contractile into a synthetic and proliferative one.
      Important roles are played by actin binding proteins like ABRA, cofilin, and
      thymosin beta 4 which determine actin polymerization and maturation. Integrins
      and connexins are markedly up-regulated. A key role in this concerted action
      which leads to a 2-to-20 fold increase in vascular diameter, depending on species
      size (mouse versus human) are the transcription factors AP-1, egr-1, carp, ets,
      by the Rho pathway and by the Mitogen Activated Kinases ERK-1 and -2. In spite of
      the enormous increase in tissue mass (up to 50-fold) the degree of functional
      restoration of blood flow capacity is incomplete and ends at 30% of maximal
      conductance (coronary) and 40% in the vascular periphery. The process of
      arteriogenesis can be drastically stimulated by increases in FSS (arterio-venous
      fistulas) and can be completely blocked by inhibition of NO production, by
      pharmacological blockade of VEGF-A and by the inhibition of the Rho-pathway.
      Pharmacological stimulation of arteriogenesis, important for the treatment of
      arterial occlusive diseases, seems feasible with NO donors.

PMID- 19101751
TI  - Green and black tea are equally potent stimuli of NO production and vasodilation:
      new insights into tea ingredients involved.
AB  - Epidemiological studies suggest that consumption of tea is associated with
      beneficial cardiovascular effects. Since different types of tea are consumed
      throughout the world, a question of much interest is whether green tea is
      superior to black tea in terms of cardiovascular protection. We therefore
      compared the effects of green and black tea on nitric oxide (NO) production and
      vasodilation and elucidated the tea compounds involved. We chose a highly
      fermented black tea and determined concentrations of individual tea compounds in
      both green and black tea of the same type (Assam). The fermented black tea was
      almost devoid of catechins. However, both teas stimulated eNOS activity and
      phosphorylation in bovine aortic endothelial cells (BAEC) as well as
      vasorelaxation in rat aortic rings to a similar extent. In green tea, only
      epigallocatechin-3-gallate (EGCG) resulted in pronounced NO production and NO
      dependent vasorelaxation in aortic rings. During tea processing to produce black
      tea, the catechins are converted to theaflavins and thearubigins. Individual
      black tea theaflavins showed a higher potency than EGCG in NO production and
      vasorelaxation. The thearubigins in black tea are highly efficient stimulators of
      vasodilation and NO production. Green and black tea compounds induced comparable
      phosphorylation of eNOS and upstream signalling kinases. Whereas stimulation of
      eNOS activity by EGCG was only slightly affected by pretreatment of cells with
      various ROS scavengers, TF3(theaflavin-3',3-digallate)-induced eNOS activity was
      partially inhibited by PEG-catalase. These results implicate that highly
      fermented black tea is equally potent as green tea in promoting beneficial
      endothelial effects. Theaflavins and thearubigins predominantly counterbalance
      the lack of catechins in black tea. The findings may underline the contribution
      of black tea consumption in prevention of cardiovascular diseases.

PMID- 19101753
TI  - Abstracts of non-discussed poster presentations of the 33rd Annual International
      Urogynecological Association (IUGA) Meeting. Taipei, Taiwan. September 13-17,
      2008.

PMID- 19101752
TI  - Pressor response to passive walking-like exercise in spinal cord-injured humans.
AB  - OBJECTIVE: To examine blood pressure responses during passive walking-like
      exercise in the standing posture (PWE) in spinal cord-injured (SCI) humans.
      METHODS: Twelve motor-complete SCI individuals (cervical level 6 to thoracic
      level 12, ASIA grade: A or B) and twelve able-bodied controls (CON) participated
      in this study. SCI individuals were divided into a group with injury level at or
      above thoracic (T) 6 (HSCI, n = 7) and a group with injury level at or below T10
      (LSCI, n = 5). Subjects carried out 6-minute quiet standing and then 12-minute
      PWE at 1 Hz using a gait training apparatus that enables subjects to stand and
      move their legs passively. RESULTS: Mean arterial blood pressures (MAPs) at
      standing in HSCI, LSCI and CON were 69 +/- 5, 83 +/- 4 and 93 +/- 2 mmHg,
      respectively. MAP changed significantly during PWE only in HSCI and CON,
      increasing to 88 +/- 4 (P < 0.001) and 98 +/- 1 mmHg (P < 0.01), respectively.
      The former group showed a larger increase in MAP (P < 0.001). INTERPRETATION:
      Spinal sympathetic reflexes can be induced in a region isolated from the
      brainstem in response to a stimulus originating below the level of the spinal
      cord injury, and the magnitude of increase in blood pressure is greater in SCI
      individuals with lesion level at or above T6 due to loss of supraspinal control
      of the major sympathetic outflow. This central mechanism may be one of the
      reasons why greater pressor response to PWE was observed in HSCI.

PMID- 19101754
TI  - Effect of daily oral minodronate on vertebral fractures in Japanese
      postmenopausal women with established osteoporosis: a randomized placebo
      controlled double-blind study.
AB  - SUMMARY; A randomized placebo-controlled trial was conducted to examine the
      effect of daily oral 1 mg minodronate on vertebral fractures in 704
      postmenopausal women with established osteoporosis for 24 months. Minodronate
      treatment reduced vertebral fractures by 59% without serious adverse events.
      Minodronate is a safe and effective bisphosphonate for osteoporosis treatment.
      INTRODUCTION: Minodronate increases bone mineral density (BMD) in postmenopausal
      osteoporotic patients. However, its efficacy in reducing osteoporotic fractures
      has not been tested. METHODS: To examine anti-fracture efficacy and safety of
      daily oral minodronate in postmenopausal women with established osteoporosis, a
      randomized, double-blind, placebo-controlled trial was conducted in 704
      postmenopausal women (55 to 80 years) with one to five vertebral fractures and
      low BMD. Subjects were randomly assigned to receive daily oral 1 mg minodronate
      (n = 359) or placebo (n = 345) for 24 months, with daily supplements of 600 mg
      calcium and 200 IU vitamin D(3). RESULTS: Daily 1 mg minodronate for 24 months
      reduced the risk of vertebral fractures by 59% (95% CI, 36.6-73.3%). Furthermore,
      when fractures during the first 6 months were eliminated, the risk of vertebral
      fractures from 6 to 24 months was reduced by 74% in minodronate-treated group.
      Minodronate treatment also reduced height loss. Bone turnover markers were
      suppressed by about 50% after 6 months of minodronate treatment and remained
      suppressed thereafter. The overall safety profile including gastrointestinal
      safety was similar between the two groups. CONCLUSIONS: Daily oral minodronate is
      safe, well-tolerated, and is effective in reducing vertebral fracture risk in
      postmenopausal women with established osteoporosis.

PMID- 19101755
TI  - High-dose oral vitamin D3 supplementation in the elderly.
AB  - SUMMARY: Daily dosing with vitamin D often fails to achieve optimal outcomes, and
      it is uncertain what the target level of 25-hydroxyvitamin D should be. This
      study found that large loading doses of vitamin D(3) rapidly and safely normalize
      25OHD levels, and that monthly dosing is similarly effective after 3-5 months.
      With baseline 25OHD > 50 nmol/L, vitamin D supplementation does not reduce PTH
      levels. INTRODUCTION: There is concern that vitamin D supplementation doses are
      frequently inadequate, and that compliance with daily medication is likely to be
      suboptimal. METHODS: This randomized double-blind trial compares responses to
      three high-dose vitamin D(3) regimens and estimates optimal 25-hydroxyvitamin D
      (25OHD) levels, from changes in parathyroid hormone (PTH), and procollagen type I
      amino-terminal propeptide (P1NP) in relation to baseline 25OHD. Sixty-three
      elderly participants were randomized to three regimens of vitamin D
      supplementation: a 500,000-IU loading dose; the loading dose plus 50,000
      IU/month; or 50,000 IU/month. RESULTS: The Loading and Loading + Monthly groups
      showed increases in 25OHD of 58 +/- 28 nmol/L from baseline to 1 month.
      Thereafter, levels gradually declined to plateaus of 69 +/- 5 nmol/L and 91 +/- 4
      nmol/l, respectively. In the Monthly group, 25OHD reached a plateau of ~80 +/- 20
      nmol/L at 3-5 months. There were no changes in serum calcium concentrations. PTH
      and P1NP were only suppressed by vitamin D treatment in those with baseline 25OHD
      levels <50 and <30 nmol/L, respectively. CONCLUSIONS: Large loading doses of
      vitamin D(3) rapidly and safely normalize 25OHD levels in the frail elderly.
      Monthly dosing is similarly effective and safe, but takes 3-5 months for plateau
      25OHD levels to be reached.

PMID- 19101756
TI  - Therapeutic effect of anti-vascular endothelial growth factor receptor I antibody
      in the established collagen-induced arthritis mouse model.
AB  - Synovial angiogenesis plays an important role in the inflammation in rheumatoid
      arthritis (RA). Vascular endothelial growth factor (VEGF) is a key molecule in
      angiogenesis and binds to specific receptors, known as vascular endothelial
      growth factor receptor I (VEGF RI). In this study, we investigated the
      therapeutic efficacy of anti-VEGF RI antibody (Ab) on RA using a collagen-induced
      arthritis (CIA) mouse model. Twelve DBA/1 mice were divided into three groups.
      All mice except controls were injected with type II collagen. Mice in the anti
      VEGF-RI-Ab-treated groups were injected on one posterior paw with 50 microg anti
      VEGF RI Ab twice weekly for 3 weeks. Arthritis score and paw thickness were
      measured and histopathologic assessment of joint sections was performed by
      hematoxylin-eosin. The infiltration of CD45+ inflammatory cells and
      neovascularization were evaluated by immunohistochemical staining. Anti-VEGF RI
      Ab significantly attenuated the arthritis severity and histopathologic findings
      in the CIA mice model. The infiltration of CD45+ cells decreased in anti-VEGF-RI
      Ab-treated joint tissues. Staining for CD31 revealed reduced synovial
      neovascularization after anti-VEGF RI Ab treatment. The data showing that in vivo
      administration of anti-VEGF RI Ab suppressed arthritis in established CIA mice
      suggest anti-VEGF RI Ab treatment may serve as a new therapeutic modality for RA.

PMID- 19101758
TI  - Can aesthetic surgeons be true artists?

PMID- 19101757
TI  - Successful treatment for sympathetic storms in a patient with neuro-Behcet's
      disease.
AB  - Sympathetic storms (SyS) are characterized by hyperactivity of autonomic
      functions, resulting in episodes of hyperthermia, hypertension, tachycardia, and
      hyperhidrosis. We show here a patient with neuro-Behcet's disease (NBD)
      complicated by SyS. Although SyS is well known to occur with brain tumors,
      trauma, and hydrocephalus, this is the first report to show that SyS is a
      manifestation of central nervous system involvement in a patient with NBD. High
      concentrations of norepinephrine (NE) and IL-8 in cerebrospinal fluid reflected
      the activity of SyS. The patient's symptoms showed almost complete improvement
      after treatment with corticosteroids and intravenous cyclophosphamide. Also, the
      concentrations of NE and IL-8 were decreased to normal levels. An awareness of
      the potential for SyS and adequate immunosuppressant therapy are of importance
      when dealing with patients with NBD.

PMID- 19101759
TI  - Effect of verapamil on reduction of peri-implant capsular thickness.
AB  - Silicone is a material commonly used in reconstructive and aesthetic surgery, but
      capsular formation is a very frequent complication of silicone implants. This
      study aimed to investigate whether verapamil, a calcium-channel blocker, can
      reduce the thickness of the peri-implant capsule in rats when it is instilled
      into the subcutaneous pockets. For this study, 60 female Wistar albino rats were
      used, and cubes of silicone blocks (10 x 10 x 5 mm) were crafted. The rats were
      divided into five groups of 12 each, and the groups were distinguished according
      to the use of silicone and artificially created hematoma relevant to
      administration of a single dose of 5 mg verapamil (Isoptin). The control group
      was left without silicone. In two of the four silicone groups, hematoma was
      artificially created around the silicone by a 1-ml injection of blood. The
      implants were removed 6 months later, and capsulectomy was performed. Under light
      microscopic examination, no severe inflammation was observed in any of the
      capsule tissues. Additionally, the thickness of the capsule was measured and
      found to be significantly reduced statistically in all the verapamil-treated
      groups, including the groups with the artificially created hematoma. In
      conclusion, based on the statistically significant data obtained in this study,
      subcutaneous verapamil administration may be a useful adjunct for preventing
      formation of capsular contracture after silicone implantations. This preliminary
      work in rats should be confirmed with larger mammals before carefully controlled
      clinical trials are considered.

PMID- 19101760
TI  - Surgical treatment of gynecomastia with severe ptosis: periareolar incision and
      dermal double areolar pedicle technique.
AB  - BACKGROUND: Gynecomastia is a morphostructural impairment of the mammary region
      in men caused by parenchymal hypertrophy or a cutaneous distortion of breast skin
      covering or both. The clinical classification introduced by Simon et al. in 1973
      ranks gynecomastia in three degrees. Each subtype can be treated with a specific
      technique. This article describes an alternative surgical procedure for treating
      gynecomastia with severe ptosis(type III and type IIIb of Simon's
      classification). METHODS: Fifty-eight patients were treated for gynecomastia in
      our Plastic Surgery Unit from 1996 to 2004. The cutaneous excess of periareolar
      skin is evaluated by a pinching test. A circular periareolar mark is traced
      corresponding to the cutaneous excess that has to be removed.Initially,
      liposuction of adipous tissue on the periphery of the mammary region is performed
      through two cutaneous 3-mm incisions at the 3 o'clock and 9 o'clock positions
      around the areola. After this, the liposuction incisions are enlarged from 10
      o'clock to 8 o'clock and from 2 o'clockto 4 o'clock to create access for the
      mastectomy. This dissection creates a double dermal areolar pedicle. The new
      areolar position is fixed with a Benelli round block suture. RESULTS: A
      resolution of the morphologic deformity without evident scars after hair growth
      and a correction of the breast deformity has been observed in the 6-month follow
      ups conducted for all the patients. CONCLUSION: We observed that the vascular
      nervous net under the areola at 12 o'clock and 6 o'clock is very important, more
      so than the lateral pedicle, and the conservation of a double vascular-nervous
      pedicle reduces significantly the risk of areolar necrosis, especially in cases
      of gynecomastia type III and in cases where there is a high degree of breast
      malformation such as the tuberous breast.

PMID- 19101761
TI  - Arctic lake physical processes and regimes with implications for winter water
      availability and management in the National Petroleum Reserve Alaska.
AB  - Lakes are dominant landforms in the National Petroleum Reserve Alaska (NPRA) as
      well as important social and ecological resources. Of recent importance is the
      management of these freshwater ecosystems because lakes deeper than maximum ice
      thickness provide an important and often sole source of liquid water for aquatic
      biota, villages, and industry during winter. To better understand seasonal and
      annual hydrodynamics in the context of lake morphometry, we analyzed lakes in two
      adjacent areas where winter water use is expected to increase in the near future
      because of industrial expansion. Landsat Thematic Mapper and Enhanced Thematic
      Mapper Plus imagery acquired between 1985 and 2007 were analyzed and compared
      with climate data to understand interannual variability. Measured changes in lake
      area extent varied by 0.6% and were significantly correlated to total
      precipitation in the preceding 12 months (p < 0.05). Using this relation, the
      modeled lake area extent from 1985 to 2007 showed no long-term trends. In
      addition, high-resolution aerial photography, bathymetric surveys, water-level
      monitoring, and lake-ice thickness measurements and growth models were used to
      better understand seasonal hydrodynamics, surface area-to-volume relations,
      winter water availability, and more permanent changes related to geomorphic
      change. Together, these results describe how lakes vary seasonally and annually
      in two critical areas of the NPRA and provide simple models to help better
      predict variation in lake-water supply. Our findings suggest that both
      overestimation and underestimation of actual available winter water volume may
      occur regularly, and this understanding may help better inform management
      strategies as future resource use expands in the NPRA.

PMID- 19101762
TI  - Abstracts of the BSIR 2008 Annual Meeting. November 5-7, 2008. Manchester, United
      Kingdom.

PMID- 19101765
TI  - Establishing prognosis in retroperitoneal sarcoma: a new histology-based
      paradigm.
AB  - BACKGROUND: Retroperitoneal sarcoma (RPS) American Joint Committee on Cancer
      (AJCC) staging applies to primary tumors only; due to specific RPS disease
      characteristics, staging is driven primarily by grade, stratifying patients into
      only two distinct prognostic subsets. The objective of this study was to help
      improve currently available staging for RPS by establishing a new, more robust
      histology-based prognostic system. METHODS: A RPS database of 1,118 patients seen
      at our institution (1996-2006) identified 343 patients treated for resectable
      primary or recurrent disease; a histologic subtype-based RPS prognostic system
      was designed and evaluated for prognostic accuracy in comparison with the current
      AJCC staging system. RESULTS: Histology stratified patients into three groups by
      prognosis (P<0.0002): atypical lipomatous tumor (ALT), non-ALT liposarcoma (LPS),
      and "other," an improvement compared with AJCC staging which could only identify
      two distinct prognostic groups. In contrast to AJCC staging, this prognostic
      stratification was reproducible for both primary and recurrent RPS (P<0.0001).
      After multivariate analysis, LPS (P=0.0004) and "other" histologies (P<0.0001)
      were found to be independent predictors of worse survival. The concordance ratio
      of this model was 0.74, equivalent to that of the model using the AJCC staging
      system. CONCLUSIONS: A histology-based RPS prognostic system has two advantages
      over AJCC staging: it can stratify into three versus two distinct prognostic
      groups, and it can be used for both primary and recurrent RPS. Distinct risk
      stratification is critical for specific assessment of prognosis as well as
      decisions regarding individualized adjuvant therapies, hence the advantage of a
      three-tiered histology-based system applicable in both primary and recurrent RPS.

PMID- 19101763
TI  - Proteomics of juvenile senegal sole (Solea senegalensis) affected by gas bubble
      disease in hyperoxygenated ponds.
AB  - Solea senegalensis is a commercial flat fish traditionally farmed in earth ponds
      in coastal wetlands that might also become important to more intensive
      aquaculture. Gas bubble disease (GBD) is a potential risk for outdoor fish
      farming, particularly in certain periods of the year, related to improper
      management leading to macroalgae blooms. Physical-chemical conditions inducing
      hyperoxia, including radiation, temperature, and high levels of dissolved oxygen,
      have been monitored in fish affected by GBD together with observed symptoms.
      Exophthalmia, subcutaneous emphysemas, obstruction of gill lamellae, hemorrhages,
      and anomalous swimming were the main effects of oxygen supersaturation. A
      proteomic study was carried out for the first time under aquaculture conditions
      and protein expression changes are described for fish that were subject to
      hyperoxic conditions. Proteins identified in gill of GBD-affected fish are
      related to oxidative alteration of cytoskeleton structure/function (beta-tubulin,
      beta-actin), motility (light myosin chain, alpha-tropomyosin), or regulatory
      pathways (calmodulin, Raf kinase inhibitor protein), reflecting the central role
      of gill in oxygen exchange. Hepatic proteins identified are related to protein
      oxidative damages (beta-globin, FABPs), protection from oxidative stress (DCXR,
      GNMT), and inflammatory response (C3), in agreement with the predominant
      metabolic role of liver. Comparison of protein expression patterns and protein
      identification are suggested as potentially specific hyperoxia biomarkers that
      would facilitate prevention of GBD outbreaks.

PMID- 19101766
TI  - Method of detection of initial recurrence of stage II/III cutaneous melanoma:
      analysis of the utility of follow-up staging.
AB  - BACKGROUND: The follow-up of patients with cutaneous melanoma is controversial.
      Current recommendations suggest routine history and physical examination every 3
      to 6 months for the first 3 years and correlate studies including laboratory
      tests and radiographic imaging. However, the utility of these recommendations are
      unclear. The purpose of this study was to determine the impact of routine imaging
      on the method of detection of first recurrence in patients with stage II and
      sentinel lymph node-positive stage III melanoma. METHODS: We analyzed a
      prospective database of all cutaneous melanoma patients treated at our
      institution from 1997 to 2005 who had at least 2 years of follow-up. The method
      of detection of initial recurrence was analyzed. RESULTS: One hundred eighteen
      patients with stage II (n = 83) or III (n = 35) melanoma who were followed for at
      least 2 years were identified. Forty-three of these patients developed recurrence
      (median time to recurrence, 14 months). Site of first recurrence was as follows:
      4 local, 17 in transit, 7 regional lymph node, and 15 distant. Twenty-nine
      recurrences (67%) were either patient detected or symptomatic. Eleven (26%) were
      detected by the physician at routine follow-up. Only three (7%) were identified
      by imaging (two chest X-ray and one brain magnetic resonance imaging) in an
      otherwise asymptomatic patient. CONCLUSIONS: Two-thirds of all initial
      recurrences of cutaneous melanoma were either detected by a patient or were
      symptomatic, with most of the remainder detected during routine physical
      examination. Routine imaging added little value in the detection of initial
      recurrence.

PMID- 19101767
TI  - Port-A-Cath implantation using percutaneous puncture without guidance.
AB  - BACKGROUND: The implantation of a Port-A-Cath (PAC) is a common surgical
      procedure usually done under guidance with techniques such as fluoroscopy,
      ultrasound, or intravenous electrocardiography. PAC implantation without guidance
      avoids radiation exposure and decreases time, expense, and complexity. The
      purpose of this study was to analyze the success rate, and operation-related and
      postoperative complications of PAC implantation without intraoperative guidance.
      METHODS: Between July 2004 and June 2007, 1,070 PACs were implanted in 1,025
      patients receiving chemotherapy. All PACs were placed via the subclavian vein by
      percutaneous puncture. The catheter length was precalculated for each patient.
      Postoperative chest radiography was immediately performed to check the catheter
      position. All data on outcome of the implantations were reviewed retrospectively.
      RESULTS: The catheter tip was correctly placed at the cavoatrial junction without
      complications in 1,055/1,070 (98.6%) of the implants. Surgery-related
      complications occurred in 15 (1.4%) implantations: 9 malposition, 3 pneumothorax,
      2 hematoma, and 1 catheter kinking. Two patients underwent PAC removal due to
      hematoma with subsequent wound infection in one and catheter occlusion by kinking
      in the other. There were 86 (8.0%) postoperative complications that resulted in
      PAC removal: catheter occlusion in 24 (2.2%), pocket infection in 22 (2.1%),
      catheter rupture in 11 (1.0%), venous thrombosis in 9 (0.8%), port exposure in 9
      (0.8%), catheter fracture in 6 (0.6%), infraclavicular pain in 3 (0.3%), catheter
      migration in 1 (0.1%), and extraportal injection in 1 (0.1%). CONCLUSIONS: PACs
      can be safely and accurately placed using percutaneous puncture of the subclavian
      vein without intraoperative guidance.

PMID- 19101768
TI  - Patterns of axillary surgical care for breast cancer in the era of sentinel lymph
      node biopsy.
AB  - BACKGROUND: Population-based overall patterns of surgical management of the
      axilla in women with operable breast cancer during the era of adoption of
      sentinel lymph node biopsy (SLNB) were studied. METHODS: Women with operable
      breast carcinoma residing in 14 geographic areas of the Surveillance,
      Epidemiology, and End Results (SEER) cancer registries (1998-2004, n=239,661)
      were assessed for axillary surgical patterns of care. RESULTS: Use of SLNB
      increased from 11 to 59%. Use of no axillary surgery decreased from 14 to 6.6%.
      In pathologic node-negative women, use of axillary lymph node dissection (ALND)
      decreased from 94 to 36%. Independent factors most associated with failure to
      receive SLNB included diagnosis year (2000: 62%; 2004: 29%), surgery (mastectomy:
      64%; breast-conserving surgery: 36%), tumor size (T3: 71%; T2: 56%; T1: 40%), age
      (>or= 70 years: 50%; <70 years: 45%), grade (high: 42%; low: 38%), urbanity (non
      large metropolitan area: 49%; large metropolitan area: 42%), and, by quartile,
      poverty (highest: 47%; lowest: 35%), and white-collar employment (lowest: 56%;
      highest: 47%). In pathologic node-positive women who had SLNB, failure to undergo
      completion ALND increased from 20% in 1998 to 32% in 2004. Patients with smaller,
      lower-grade tumors, and those with smaller size of nodal metastasis, lack of
      extracapsular extension, age >or= 70 years, increased linguistic isolation,
      African-American or Hispanic race/ethnicity, and white-collar employment were
      less likely to undergo completion ALND. CONCLUSIONS: Management of the axilla
      changed dramatically during the period of rapid adoption of SLNB. Patterns of
      care suggest both appropriate and inappropriate selection for SLNB and ALND.

PMID- 19101769
TI  - Modeling the evolution of insect phenology.
AB  - Climate change is likely to disrupt the timing of developmental events
      (phenology) in insect populations in which development time is largely determined
      by temperature. Shifting phenology puts insects at risk of being exposed to
      seasonal weather extremes during sensitive life stages and losing synchrony with
      biotic resources. Additionally, warming may result in loss of developmental
      synchronization within a population making it difficult to find mates or mount
      mass attacks against well-defended resources at low population densities. It is
      unknown whether genetic evolution of development time can occur rapidly enough to
      moderate these effects. We present a novel approach to modeling the evolution of
      phenology by allowing the parameters of a phenology model to evolve in response
      to selection on emergence time and density. We use the Laplace method to find
      asymptotic approximations for the temporal variation in mean phenotype and
      phenotypic variance arising in the evolution model that are used to characterize
      invariant distributions of the model under periodic temperatures at leading
      order. At these steady distributions the mean phenotype allows for parents and
      offspring to be oviposited at the same time of year in consecutive years.
      Numerical simulations show that populations evolve to these steady distributions
      under periodic temperatures. We consider an example of how the evolution model
      predicts populations will evolve in response to warming temperatures and shifting
      resource phenology.

PMID- 19101770
TI  - Efficient reconstruction of metabolic pathways by bidirectional chemical search.
AB  - One of the main challenges in systems biology is the establishment of the
      metabolome: a catalogue of the metabolites and biochemical reactions present in a
      specific organism. Current knowledge of biochemical pathways as stored in public
      databases such as KEGG, is based on carefully curated genomic evidence for the
      presence of specific metabolites and enzymes that activate particular biochemical
      reactions. In this paper, we present an efficient method to build a substantial
      portion of the artificial chemistry defined by the metabolites and biochemical
      reactions in a given metabolic pathway, which is based on bidirectional chemical
      search. Computational results on the pathways stored in KEGG reveal novel
      biochemical pathways.

PMID- 19101771
TI  - Threshold conditions for west nile virus outbreaks.
AB  - In this paper, we study the stability and saddle-node bifurcation of a model for
      the West Nile virus transmission dynamics. The existence and classification of
      the equilibria are presented. By the theory of K-competitive dynamical systems
      and index theory of dynamical systems on a surface, sufficient and necessary
      conditions for local stability of equilibria are obtained. We also study the
      saddle-node bifurcation of the system. Explicit subthreshold conditions in terms
      of parameters are obtained beyond the basic reproduction number which provides
      further guidelines for accessing control of the spread of the West Nile virus.
      Our results suggest that the basic reproductive number itself is not enough to
      describe whether West Nile virus will prevail or not and suggest that we should
      pay more attention to the initial state of West Nile virus. The results also
      partially explained the mechanism of the recurrence of the small scale endemic of
      the virus in North America.

PMID- 19101772
TI  - An "age"-structured model of hematopoietic stem cell organization with
      application to chronic myeloid leukemia.
AB  - Previously, we have modeled hematopoietic stem cell organization by a stochastic,
      single cell-based approach. Applications to different experimental systems
      demonstrated that this model consistently explains a broad variety of in vivo and
      in vitro data. A major advantage of the agent-based model (ABM) is the
      representation of heterogeneity within the hematopoietic stem cell population.
      However, this advantage comes at the price of time-consuming simulations if the
      systems become large. One example in this respect is the modeling of disease and
      treatment dynamics in patients with chronic myeloid leukemia (CML), where the
      realistic number of individual cells to be considered exceeds 10(6). To overcome
      this deficiency, without losing the representation of the inherent heterogeneity
      of the stem cell population, we here propose to approximate the ABM by a system
      of partial differential equations (PDEs). The major benefit of such an approach
      is its independence from the size of the system. Although this mean field
      approach includes a number of simplifying assumptions compared to the ABM, it
      retains the key structure of the model including the "age"-structure of stem
      cells. We show that the PDE model qualitatively and quantitatively reproduces the
      results of the agent-based approach.

PMID- 19101773
TI  - Asking the right questions: views on genetic variation research among black and
      white research participants.
AB  - BACKGROUND: Genetic variation research (GVR) may raise concerns about misuse of
      information and discrimination. Seemingly contradictory positive views about GVR
      have also been reported. OBJECTIVE: To dissect this inconsistency, our objectives
      were to: (1) explore open-ended views of GVR and (2) quantify views of and
      willingness to participate in GVR by race. DESIGN: Cross-sectional study.
      PARTICIPANTS: 801 African-American and white prior participants in a case-control
      genetic epidemiology study of colon cancer risks (NCCCS). MEASURES: Qualitative
      measures evaluated responses to questions about good and bad things about GVR.
      Quantitative measures evaluated positive and negative perceptions, perceptions of
      discrimination, and likelihood of future participation by race. RESULTS: Open
      ended queries about GVR resulted in few "negative" responses. In closed-ended
      questions, however, African Americans were more likely to feel that such research
      would: result in higher insurance (41% vs. 30%, p = 0.008), not benefit
      minorities (29% vs. 14%, p=<0.001), reinforce racism (32% vs. 20%, p = 0.002),
      and use minorities as guinea pigs (27% vs. 6%, p < 0.001). Overall, after
      adjustment for potential confounding factors, African-American race remained
      inversely associated with feeling "very positive" about GVR (46% vs. 57%, p =
      0.035). In contrast, African Americans were as likely as whites to express
      willingness to participate in future GVR studies (46%). CONCLUSIONS: Open-ended
      questions about GVR were unlikely to spontaneously generate "negative" responses.
      In contrast, when presented specific examples of potentially negative
      implications, more respondents agreed, and minorities were more likely to express
      concerns. This suggests that while participants appear generally positive about
      GVR, their inability to articulate views regarding these complex concepts may
      require that researchers engage lay audiences, ensure accurate understanding, and
      provide them with language to express concerns.

PMID- 19101775
TI  - High medical cost burdens, patient trust, and perceived quality of care.
AB  - BACKGROUND: The financial burden of medical care expenses is increasing for
      American families. However, the association between high medical cost burdens and
      patient trust in physicians is not known. OBJECTIVE: To examine the association
      between high medical cost burdens and self-reported measures of patient trust and
      perceived quality of care. METHODS: Cross-sectional household survey based on
      random-digit dialing and conducted largely by telephone, supplemented by in
      person interviews of households with no telephones. The sample for this analysis
      includes 32,210 adults who reported having a physician as their regular source of
      care. Measures of patient trust include overall trust, confidence in being
      referred to a specialist, and belief that the physician uses more services than
      necessary. Perceived quality measures include thoroughness of exam, ability to
      listen, and ability to explain. RESULTS: In adjusted analyses, persons with high
      medical cost burdens had greater odds of lacking trust in their physician to put
      their needs above all else (OR = 1.43, CI = 1.19, 1.73), not referring them to
      specialists (OR = 1.39, CI = 1.22, 1.58), and performing unnecessary tests (OR =
      1.42, CI = 1.20, 1.62). Patients with high medical cost burdens also had more
      negative assessments of the thoroughness of care they receive from their
      physician (OR = 1.26, CI = 1.02, 1.56). The association of high medical cost
      burdens with patient trust and perceived quality of care was greatest for
      privately insured persons. CONCLUSION: The rising cost of medical care threatens
      a vital aspect of the effective delivery of medical care-patient trust in their
      physician and continuity of care. Exposing patients to more of the costs could
      lead to greater skepticism and less trust of physicians' decision-making, thereby
      making health-care delivery less effective.

PMID- 19101774
TI  - Association of communication between hospital-based physicians and primary care
      providers with patient outcomes.
AB  - BACKGROUND: Patients admitted to general medicine inpatient services are
      increasingly cared for by hospital-based physicians rather than their primary
      care providers (PCPs). This separation of hospital and ambulatory care may result
      in important care discontinuities after discharge. We sought to determine whether
      communication between hospital-based physicians and PCPs influences patient
      outcomes. METHODS: We approached consecutive patients admitted to general
      medicine services at six US academic centers from July 2001 to June 2003. A
      random sample of the PCPs for consented patients was contacted 2 weeks after
      patient discharge and surveyed about communication with the hospital medical
      team. Responses were linked with the 30-day composite patient outcomes of
      mortality, hospital readmission, and emergency department (ED) visits obtained
      through follow-up telephone survey and National Death Index search. We used
      hierarchical multi-variable logistic regression to model whether communication
      with the patient's PCP was associated with the 30-day composite outcome. RESULTS:
      A total of 1,772 PCPs for 2,336 patients were surveyed with 908 PCPs responses
      and complete patient follow-up available for 1,078 patients. The PCPs for 834
      patients (77%) were aware that their patient had been admitted to the hospital.
      Of these, direct communication between PCPs and inpatient physicians took place
      for 194 patients (23%), and a discharge summary was available within 2 weeks of
      discharge for 347 patients (42%). Within 30 days of discharge, 233 (22%) patients
      died, were readmitted to the hospital, or visited an ED. In adjusted analyses, no
      relationship was seen between the composite outcome and direct physician
      communication (adjusted odds ratio 0.87, 95% confidence interval 0.56 - 1.34),
      the presence of a discharge summary (0.84, 95% CI 0.57-1.22), or PCP awareness of
      the index hospitalization (1.08, 95% CI 0.73-1.59). CONCLUSION: Analysis of
      communication between PCPs and inpatient medical teams revealed much room for
      improvement. Although communication during handoffs of care is important, we were
      not able to find a relationship between several aspects of communication and
      associated adverse clinical outcomes in this multi-center patient sample.

PMID- 19101776
TI  - Perceptions of breast cancer treatment among African-American women and men:
      implications for interventions.
AB  - BACKGROUND: While breast cancer mortality has declined in recent years, the
      mortality gap between African-American and white women continues to grow. Current
      strategies to reduce this disparity focus on logistical and information needs,
      but contextual factors, such as concerns about racism and treatment side effects,
      may also represent significant barriers to improved outcomes. OBJECTIVE: To
      characterize perceptions of breast cancer treatment among African-American women
      and men. DESIGN: A qualitative study of African-American adults using focus group
      interviews. PARTICIPANTS: Two hundred eighty women and 165 men who live in one of
      15 contiguous neighborhoods on Chicago's South Side. APPROACH: Transcripts were
      systematically analyzed using qualitative techniques to identify emergent themes
      related to breast cancer treatment. RESULTS: The concerns expressed most
      frequently were mistrust of the medical establishment and federal government, the
      effect of racism and lack of health insurance on quality of care, the impact of
      treatment on intimate relationships, and the negative effects of surgery,
      radiation therapy, and chemotherapy. CONCLUSIONS: In addition to providing
      logistical and information support, strategies to reduce the breast cancer
      mortality gap should also address contextual factors important to quality of
      care. Specific interventions are discussed, including strategies to enhance
      trust, reduce race-related treatment differences, minimize the impact of
      treatment on intimate relationships, and reduce negative perceptions of breast
      cancer surgery, radiation therapy, and chemotherapy.

PMID- 19101779
TI  - Preoperative weight loss in bariatric surgery.

PMID- 19101777
TI  - Dual use of VA and non-VA services among primary care patients with depression.
AB  - BACKGROUND: Depression treatment requires close monitoring to achieve optimal,
      long-term control. Use of multiple sources of health care can affect coordination
      and continuity of treatment for depression. OBJECTIVES: To assess levels of non
      Veterans Health Administration (VA) use among depressed primary care patients by
      service type and examine patient factors associated with non-VA use. DESIGN:
      Cross-sectional comparison of dual and VA-only users among depressed primary care
      patients. Depression was defined as PHQ-9 >or=10. SUBJECTS: Five hundred fifty
      depressed patients from the baseline sample of a group-randomized trial of
      collaborative care for depression in ten VA primary care practices. MEASUREMENTS:
      VA and non-VA outpatient utilization for physical and emotional health problems
      in the prior 6 months, patient demographics, and co-morbid conditions. All
      measures were self-reported and obtained at the baseline interview. RESULTS:
      Overall, 46.8% of VA depressed primary care patients utilized non-VA care. Dual
      users were more likely to use acute care services (emergency room or inpatient),
      especially for physical health problems. Dual users of physical health services
      had more total visits, but fewer VA visits than VA-only users, while dual users
      of emotional health services had fewer total and VA visits. Factors associated
      with dual use were urban clinic location, having other insurance coverage, and
      dissatisfaction with physical health care in general. CONCLUSIONS: Almost half of
      depressed primary care patients used non-VA care, with most of their non-VA use
      for physical rather than emotional health problems. Care management strategies
      for depressed patients should include communication and coordination with non-VA
      providers.

PMID- 19101780
TI  - Olmesartan clinical trial in Okinawan patients under OKIDS (OCTOPUS) study:
      design and methods.
AB  - BACKGROUND: Guidelines for treatment of hypertension are not available for
      chronic hemodialysis (HD) population, despite the high mortality rate due to
      cardiovascular disease (CVD). Survival is much better among hypertensive patients
      than normal to hypotensive patients. Target levels of blood pressure and the
      class of antihypertensive drugs have not been examined in prospective studies.
      METHODS: We designed a prospective randomized controlled study among hypertensive
      HD patients in Okinawa (Okinawa Dialysis Study, OKIDS). The outcomes will be
      compared between two treatment regimens, such as (1) renin-angiotensin system
      (RAS) inhibitor Olmesartan and others, and (2) antihypertensive drugs without RAS
      inhibitors, in a parallel fashion. The title of the study is Olmesartan Clinical
      Trial in Okinawan Patients under OKIDS (OCTOPUS). Outcomes are any cause of death
      and CVD in 3 years in a total of 462 patients. Subjects are age 20-79 years and
      ambulatory on thrice weekly HD treatment. Eligible patients have resistant
      hypertension: pre-HD session blood pressure 140/90 mmHg and over for more than 1
      month regardless with the use of antihypertensive drugs. Patients treated with
      RAS drugs are eligible if they continue to be hypertensive for more than 1 month
      after switching to non-RAS antihypertensive drugs. CONCLUSION: This study
      provides evidence for the target levels of blood pressure at a pre-HD session and
      the impact of RAS inhibitors. We also evaluate the usefulness of home blood
      pressure monitoring in HD patients.

PMID- 19101781
TI  - Chronic myeloid leukemia in Asia.
AB  - Chronic myeloid leukemia (CML) in Asia has an incidence rather lower than in
      Western countries yet tends to afflict a younger population. As in the West,
      imatinib mesylate (IM, Glivec) has supplanted busulphan, hydroxyurea and
      interferon-alpha as first-line treatment. Its use has resulted in a dramatic
      decline in the number of hematopoietic stem cell transplantations (HSCT)
      performed. Although it is expensive, IM induces a complete cytogenetic response
      in 60-90% of newly diagnosed patients, and up to 10% for those in blastic phase.
      The standard dose of 400 mg is well tolerated by most patients, although adverse
      events have been observed, including drug-induced cytopenia. Through the Glivec
      International Patient Assistance Program, the majority of CML patients has access
      to IM and can expect prolonged survival, even in the absence of HSCT. However,
      just as in Western countries, resistance to imatinib has emerged in Asian
      countries. They will require the novel tyrosine kinase inhibitors (dasatinib,
      nilotinib) becoming available through either clinical trials or market approval.
      This review examines the available data on CML in China, Hong Kong, India, the
      Philippines, Singapore, South Korea, Taiwan and Thailand.

PMID- 19101782
TI  - Development of rapid light-chain deposition disease in hepatic arteries with
      severe ischemic cholangitis in a multiple myeloma patient treated with melphalan,
      prednisone and lenalidomide.
AB  - Light-chain deposition disease (LCDD) is a multisystemic disorder associated with
      plasma cell dyscrasias and multiple myeloma. It is histologically characterized
      by the deposition of a homogeneous, in electron microscopy granular, slightly
      eosinophilic material showing positivity usually for kappa light chains. In
      contrast to AL-amyloidosis, the material is negative for Congo red. LCDD mainly
      involves the kidneys as the predominant organ manifestation resulting in a
      nephrotic syndrome. However, involvement of other tissues such as liver and heart
      have been described. Here we report a case of severe ischemic cholangitis in a
      patient with multiple myeloma receiving chemotherapy with melphalan, prednisone,
      and lenalidomide. Histopathological analysis revealed LCDD of the hepatic
      arteries as the underlying cause. This is to our knowledge the first case of LCDD
      of terminal liver arteries as a cause of intrahepatic ischemic cholangitis.

PMID- 19101783
TI  - Efficacy and safety of optimized antithrombotic therapy with aspirin, clopidogrel
      and enoxaparin in patients with non-ST segment elevation acute coronary syndromes
      in clinical practice.
AB  - In randomized clinical trials enoxaparin in non ST-elevation acute coronary
      syndromes (NSTE-ACS) has been shown to be more effective than unfractionated
      heparin in preventing the combined endpoint of death and myocardial infarction.
      Clopidogrel in combination with aspirin reduced the combined endpoint of death,
      myocardial infarction and stroke in NSTE-ACS patients compared to aspirin alone.
      Aim of the present study was to determine the clinical impact of optimized
      antithrombotic therapy with enoxaparin, clopidogrel and aspirin compared to
      standard therapy with unfractionated heparin (UFH) and aspirin in NSTE-ACS in
      clinical practice. We analyzed data of 2,956 consecutive patients with NSTE-ACS
      and either antithrombotic therapy with enoxaparin, clopidogrel and aspirin or
      with aspirin and UFH, which were prospectively enrolled in the acute coronary
      syndromes registry (ACOS) from July 2000 until the end of November 2002. After
      adjustment for baseline characteristics and PCI the combined endpoint of hospital
      death and non-fatal reinfarctions was lower in the group with optimized
      antithrombotic therapy including clopidogrel, enoxaparin and aspirin compared to
      the control-group with aspirin and UFH (odds ratio 0.30, 95% confidence interval
      0.16-0.53). There was no significant difference in major bleedings between the
      two treatment groups (1.5% vs. 0.9%, P = 0.35), while overall there were more
      bleeding complications in the group with optimized antithrombotic therapy (4.9%
      vs. 2.0%, P = 0.005). In clinical practice optimized antithrombotic therapy with
      aspirin, clopidogrel and enoxaparin in NSTE-ACS is associated with a reduction in
      the combined endpoint of death and non-fatal reinfarctions compared to standard
      therapy with aspirin and UFH without increase in major bleeding complications.

PMID- 19101784
TI  - Solubilization, purification, and reconstitution of alpha 2 beta 1 isozyme of
      Na+/K+ -ATPase from caveolae of pulmonary smooth muscle plasma membrane:
      comparative studies with DHPC, C12E8, and Triton X-100.
AB  - We identified alpha(2), alpha(1), and beta(1) isoforms of Na(+)/K(+)-ATPase in
      caveolae vesicles of bovine pulmonary smooth muscle plasma membrane. The
      biochemical and biophysical characteristics of the alpha(2)beta(1) isozyme of
      Na(+)/K(+)-ATPase from caveolae vesicles were studied during solubilization and
      purification using the detergents 1,2-heptanoyl-sn-phosphatidylcholine (DHPC),
      poly(oxy-ethylene)8-lauryl ether (C(12)E(8)), and Triton X-100, and
      reconstitution with the phospholipid dioleoyl-phosphatidylcholine (DOPC). DHPC
      was determined to be superior to C(12)E(8), whereas C(12)E(8) was better than
      Triton X-100 in the active enzyme yields and specific activity. Fluorescence
      studies with DHPC-purified alpha(2)beta(1) isozyme of Na(+)/K(+)-ATPase elicited
      higher E1Na-E2 K transition compared with that of the C(12)E(8)- and Triton X-100
      purified enzyme. The rate of Na(+) efflux in DHPC-DOPC-reconstituted isozyme was
      higher compared to the C(12)E(8)-DOPC- and Triton X100-DOPC-reconstituted enzyme.
      Circular dichroism analysis suggests that the DHPC-purified alpha(2)beta(1)
      isozyme of Na(+)/K(+)-ATPase possessed more organized secondary structure
      compared to the C(12)E(8)- and Triton X-100-purified isozyme.

PMID- 19101785
TI  - Doxorubicin-loaded polymeric micelles based on amphiphilic polyphosphazenes with
      poly(N-isopropylacrylamide-co-N,N-dimethylacrylamide) and ethyl glycinate as side
      groups: synthesis, preparation and in vitro evaluation.
AB  - PURPOSE: To construct novel doxorubicin-loaded polymeric micelles based on
      polyphosphazenes containing N-isopropylacrylamide copolymers and evaluate their
      various properties as well as in vitro anticancer effect. METHODS: These
      amphiphilic graft polyphosphazenes PNDGP were synthesized via thermal ring
      opening polymerization and subsequent two-step substitution reaction of
      hydrophilic and hydrophobic side groups. Micellization behavior in an aqueous
      phase was confirmed by fluorescence technique, DLS and TEM. Doxorubicin (DOX) was
      physically loaded into micelles by dialysis or O/W emulsion method. CLSM and MTT
      test were applied to observe intracellular drug distribution and determine
      cytotoxicity of drug-loaded micelles on Hela and HepG2 cells lines, respectively.
      RESULTS: A series of PNDGPs with controlled substitution ratios were obtained.
      Poly(NIPAm-co-DMAA) can act as hydrophilic segments in micellular system since
      its LCST was over 37 degrees C when PNIPAm was copolymerized with DMAA. The CMC
      value was decreased with the increase of Glyet content. In addition, more
      hydrophobic group content introduced into the polymer would facilitate DOX
      encapsulation into the micelle. DOX-loaded micelle could achieve comparative
      cytotoxicity as free drug via endocytosis and succedent drug release into
      cytoplasm of cancer cells. CONCLUSIONS: The results suggest that these polymers
      might be used as potential carriers of hydrophobic anti-tumor drug for cancer
      therapy.

PMID- 19101786
TI  - A mother's heart is weighed down with stones: a phenomenological approach to the
      experience of transnational motherhood.
AB  - Although recent scholarship on transnational mothers has rigorously examined the
      effect of migration on gender constructs and ideologies, it neglects analysis of
      the lived experience of separated mothers and children. In privileging the
      exploration of transnational separations through the single analytical lens of
      gender, such research reduces the embodied distress of mothers and children to
      mere "gender false consciousness." This paper calls upon anthropologists to
      redress this oversight by undertaking a phenomenological analysis of the lived
      experience of transnational motherhood. Eschewing an analysis of mothers and
      children as isolated social roles, I show that the suffering of mothers and
      children is profoundly relational. Through analysis of the narratives of
      undocumented Salvadoran mothers residing in the U.S., I show how the strain of
      such mothers' undocumented status is lived and shouldered within the
      intersubjective space of the family.

PMID- 19101787
TI  - Role of artificial liver support in hepatic encephalopathy.
AB  - Hepatic encephalopathy (HE) refers to the reversible neuropsychiatric disorders
      observed in acute liver failure and as a complication of cirrhosis and/or portal
      hypertension. This review aims to describe the pathophysiology of HE, the
      rationale for the use of artificial liver support in the treatment of HE, the
      different concepts of artificial liver support and the results obtained. Ammonia
      has been considered central to its pathogenesis but recently an important role
      for its interaction with inflammatory responses and auto-regulation of cerebral
      hemodynamics has been suggested. Artificial liver support might be able to
      decrease ammonia and modulate inflammatory mediators and cerebral hemodynamics.
      Bioartificial liver support systems use hepatocytes in an extracorporeal device
      connected to the patient's circulation. Artificial liver support is intended to
      remove protein-bound toxins and water-soluble toxins without providing synthetic
      function. Both systems improve clinical and biochemical parameters and can be
      applied safely to patients. Clinical studies have shown that artificial liver
      support, especially albumin dialysis, is able to improve HE in acute and acute-on
      chronic liver failure. Further studies are required to better understand the
      mechanism, however, artificial liver support can be added to the therapeutic
      bundle in treating HE.

PMID- 19101789
TI  - Longitudinal change in chronic fatigue syndrome: what home-based assessments
      reveal.
AB  - The purpose of this 2-year prospective study was to compare standard self-report
      and ecologically-based outcome measures in patients with chronic fatigue syndrome
      (CFS). Standard measures assessed physical function, fatigue impact,
      psychological variables, and global impression of change ratings. Ecological
      measures included actigraphy, a structured activity record, and an electronic
      fatigue/energy diary. Results for this high functioning sample (N = 75) revealed
      that self-report global improvement was significantly associated with lower
      momentary fatigue and fatigue impact, and a higher frequency of standing up (at
      home), but not with actigraphy or psychological variables. However, actigraphy
      change was significantly correlated with change in self-report physical function.
      At follow-up, only a small minority (<20%) scored in the healthy adult range for
      fatigue impact and physical function. The findings suggest that home-based
      measures of symptom severity and physical functioning may provide evidence of
      change (or lack of change) that is important for interpreting standard self
      report outcomes in CFS.

PMID- 19101788
TI  - Ecodevelopmental contexts for preventing type 2 diabetes in Latino and other
      racial/ethnic minority populations.
AB  - Diabetes is the sixth leading cause of death in the United States and it is now
      cited along with obesity as a global epidemic. Significant racial/ethnic
      disparities exist in the prevalence of diabetes within the US, with racial and
      ethnic minorities disproportionately affected by type 2 diabetes and its
      complications. Racial/ethnic and socioeconomic factors influence the development
      and course of diabetes at multiple levels, including genetic, individual,
      familial, community and national. From an ecodevelopmental perspective, cultural
      variables assessed at one level (e.g., family level dietary practices) may
      interact with other types of variables examined at other levels (e.g., the
      availability of healthy foods within a low-income neighborhood), thus prompting
      the need for a clear analysis of these systemic relationships as they may
      increase risks for disease. Therefore, the need exists for models that aid in
      "mapping out" these relationships. A more explicit conceptualization of such
      multi-level relationships would aid in the design of culturally relevant
      interventions that aim to maximize effectiveness when applied with Latinos and
      other racial/ethnic minority groups. This paper presents an expanded
      ecodevelopmental model intended to serve as a tool to aid in the design of multi
      level diabetes prevention interventions for application with racial/ethnic
      minority populations. This discussion focuses primarily on risk factors and
      prevention intervention in Latino populations, although with implications for
      other racial/ethnic minority populations that are also at high risk for type 2
      diabetes.

PMID- 19101790
TI  - Biologic therapy of breast cancer: focus on co-inhibition of endocrine and
      angiogenesis pathways.
AB  - There remains a high unmet need for effective treatments for metastatic breast
      cancer. In recent years there have been many advances in the understanding of
      biological basis of cancer. Several cellular pathways have been identified that
      play crucial roles in causing or maintaining the cancer phenotype. Many new
      agents that target these pathways have entered the clinic or are being
      investigated. In order to improve the therapeutic efficacy seen with single-agent
      regimens, rational combinations of targeted agents are being evaluated in ongoing
      trials. The optimal sequencing and combination of agents has yet to be
      established. Endocrine and vascular endothelial growth factor pathways are the
      two most prominent pathways active in breast cancer cells and inhibition of
      either of these is associated with clinical benefit. Here we discuss the
      rationale for simultaneously targeting these pathways and highlight ongoing
      clinical trials.

PMID- 19101791
TI  - Editorial. Optimizing breast cancer patient care today and tomorrow: implications
      for clinicians.

PMID- 19101792
TI  - Optimizing aromatase inhibitor integration into initial treatment strategies in
      postmenopausal women with hormone-receptor-positive early breast cancer.
AB  - After local therapy, women with early breast cancer remain at risk of recurrence
      for an extended period. For women with hormone-receptor-positive (HR+) disease,
      the risk of relapse peaks in the first 2-3 years after surgery. Distant
      metastases, which are associated with a high risk of death from breast cancer,
      account for the majority of relapses, both early and late. Preventing distant
      metastases is therefore a primary aim of systemic adjuvant treatment. Tamoxifen
      was the mainstay of endocrine adjuvant treatment for HR+ disease, but despite its
      proven benefits, a significant proportion of patients will relapse while on
      tamoxifen therapy. The third-generation aromatase inhibitors (AIs)--letrozole,
      anastrozole, and exemestane--have recently replaced tamoxifen as the recommended
      adjuvant endocrine therapy, on the basis of greater efficacy and better
      tolerability. However, the optimal use of AIs in the adjuvant setting requires
      further investigation, including identification of the best treatment strategy.
      Although a switching strategy does reduce relapses, only upfront AI therapy can
      address the early peak of distant recurrences that occur despite tamoxifen.
      Similarly, only upfront AI therapy can avoid the life-threatening side effects
      that occur in the early years of tamoxifen therapy. Available evidence supports a
      hypothesis that upfront adjuvant AI therapy is the most appropriate treatment
      strategy for postmenopausal patients with HR+ disease. Definitive evidence awaits
      results from ongoing randomized trials.

PMID- 19101793
TI  - Are all aromatase inhibitors alike?
AB  - The anti-estrogen tamoxifen was the gold-standard adjuvant therapy for hormone
      receptor-positive (HR+) early breast cancer for several decades, but has recently
      been displaced by the third-generation aromatase inhibitors (AIs). Three AIs are
      commercially available: letrozole, anastrozole and exemestane. All are more
      effective and at least as well tolerated as tamoxifen as adjuvant therapy for HR+
      breast cancer in postmenopausal women. Despite the wealth of data comparing AIs
      with tamoxifen, it is unclear whether the three AIs are clinically equivalent,
      owing to the lack of head-to-head trials directly comparing them. Preclinical and
      small clinical studies suggest that letrozole is the most potent inhibitor of
      aromatase, reducing circulating estrogen levels to a greater degree than the
      other agents. However, whether this greater activity translates into superior
      clinical efficacy remains to be determined. In the absence of direct comparative
      data, cross-trial comparisons have been used to gain insights into any safety or
      efficacy differences. All three AIs have been compared directly with tamoxifen,
      and efficacy relative to tamoxifen has been compared across trials, although such
      analyses are complicated by differences in treatment schedules, patient
      populations and trial designs. Definitive conclusions cannot yet be drawn, but
      some important differences are coming to light, with upfront letrozole appearing
      particularly effective at preventing early distant metastasis, an event strongly
      associated with breast-cancer-related death. No safety differences between the
      AIs have yet been identified. This article explores the pharmacologic and
      clinical differences between the AIs, based on data from clinical and preclinical
      studies.

PMID- 19101794
TI  - Optimal treatment strategies in postmenopausal women with hormone-receptor
      positive and HER2-negative metastatic breast cancer.
AB  - Metastatic breast cancer (MBC) is unfortunately still considered incurable;
      treatment aims to prolong progression-free and overall survival, relieve disease
      symptoms, and maintain quality of life. Treatment can include endocrine therapy,
      radiotherapy, chemotherapy, bisphosphonates, and/or targeted therapy; which is
      used depends on the characteristics of the disease [e.g., hormone receptor
      status, disease site(s), and response to previous treatment] and the patient
      (age, comorbidity, and personal preferences). For most patients with hormone
      receptor-positive tumors, the first choice of treatment is further endocrine
      therapy, but endocrine resistance is a common problem in advanced disease.
      Several novel anticancer agents have been developed with the aim of overcoming
      endocrine resistance, many of which target intracellular signaling pathways
      implicated in disease progression or resistance. Among these, inhibitors of
      growth factor receptor tyrosine kinases and of mammalian target of rapamycin have
      shown the most promise in clinical trials. Chemotherapy is the cornerstone of MBC
      treatment in most women. Important considerations when choosing chemotherapy
      include the choice of agents, and whether to use single-agent or combination
      therapy. Anthracyclines are one of the most active cytotoxic agents currently
      used for the treatment of breast cancer, and for many women, further
      anthracycline therapy at progression or relapse would be the preferred option.
      However, lifetime exposure to anthracyclines is limited by cumulative
      cardiotoxicity, which often prevents rechallenge in later lines of therapy. Newer
      anthracycline formulations have been developed with lower cardiotoxicity than the
      conventional anthracycline doxorubicin, but these agents still impair cardiac
      function, and have maximum recommended lifetime doses. Recently, the concomitant
      use of cardioprotective agents, such as dexrazoxane, has emerged as an effective
      approach to reducing the cardiotoxic effects of anthracyclines, thus permitting
      retreatment. Bisphosphonates, which are not associated with the acute toxicities
      of cytotoxic chemotherapy drugs, are the established standard of care for
      patients with metastatic bone disease, and have greatly improved outcomes over
      the last decade. The search is ongoing for novel agents that will, hopefully,
      bring a cure closer to reality.

PMID- 19101795
TI  - Relaxin, a pleiotropic vasodilator for the treatment of heart failure.
AB  - Relaxin is a naturally occurring peptide hormone that plays a central role in the
      hemodynamic and renovascular adaptive changes that occur during pregnancy.
      Triggering similar changes could potentially be beneficial in the treatment of
      patients with heart failure. The effects of relaxin include the production of
      nitric oxide, inhibition of endothelin, inhibition of angiotensin II, production
      of VEGF, and production of matrix metalloproteinases. These effects lead to
      systemic and renal vasodilation, increased arterial compliance, and other
      vascular changes. The recognition of this has led to the study of relaxin for the
      treatment of heart failure. An initial pilot study has shown favorable
      hemodynamic effects in patients with heart failure, including reduction in
      ventricular filling pressures and increased cardiac output. The ongoing RELAX-AHF
      clinical program is designed to evaluate the effects of relaxin on the symptoms
      and outcomes in a large group of patients admitted to hospital for acute heart
      failure. This review will summarize both the biology of relaxin and the data
      supporting its potential efficacy in human heart failure.

PMID- 19101796
TI  - Levosimendan: from basic science to clinical practice.
AB  - Levosimendan is a new cardiac enhancer that exerts positive inotropic effects on
      the failing heart mediated by calcium sensitization of contractile proteins as
      well as peripheral vasodilatory effects mediated by opening of ATP-sensitive
      potassium channels in vascular smooth-muscle cells. Levosimendan is the most well
      studied calcium sensitizer in the real clinical practice, producing greater
      hemodynamic and symptomatic improvement in patients with acute heart failure
      syndromes (AHFS) than those with traditional inotropes. Immunomodulatory and anti
      apoptotic properties of levosimendan may be an additional biologic mechanism that
      prevents further cytotoxic and hemodynamic consequences of abnormal immune and
      neurohormonal responses in AHFS. Recent mortality trials showed that levosimendan
      does not improve short- and long-term prognosis in AHFS in comparison to
      dobutamine or placebo. However, in patients with a previous history of CHF and on
      beta-blocker on admission, levosimendan seems to have a beneficial effect on
      short-term mortality. According to the recent guidelines of the European Society
      of Cardiology, levosimendan is indicated in patients with symptomatic low cardiac
      output HF secondary to cardiac systolic dysfunction without severe hypotension
      (Class IIa, Level of Evidence B).

PMID- 19101797
TI  - A longitudinal analysis of depressive symptoms among Asian and Pacific Islander
      mothers at-risk for child maltreatment.
AB  - This longitudinal study examined racial differences in depressive symptoms at
      three time points among Asian, Native Hawaiian/Other Pacific Islander (NHOPI) and
      white mothers at-risk for child maltreatment (n = 616). The proportion of mothers
      with depressive symptoms ranged from 28 to 35% at all time points. Adjusted
      analyses revealed that Asian and NHOPI mothers were significantly more likely
      than white mothers to have depressive symptoms but this disparity was present
      only among families at mild/moderate risk for child maltreatment. Future research
      should identify ways to reduce this disparity and involve the Asian and NHOPI
      communities in prevention and treatment program design and implementation.

PMID- 19101798
TI  - Prospective randomized trial of argon plasma coagulation ablation versus
      endoscopic surveillance of Barrett's esophagus in patients treated with
      antisecretory medication.
AB  - Argon plasma coagulation (APC) has been used to ablate Barrett's esophagus,
      however, its role in the management of non-dysplastic Barrett's esophagus is
      uncertain. The purpose of this study is to determine the efficacy of endoscopic
      argon plasma coagulation (APC) for ablation of Barrett's esophagus in a
      prospective randomized controlled trial in two university teaching hospitals.
      Fifty-seven patients using proton pump inhibitor (PPI) medication and with
      Barrett's esophagus were randomized to undergo either ablation using endoscopic
      argon plasma coagulation (APC) or ongoing surveillance. Fifty-one patients
      underwent endoscopy at 12 months. Endoscopic argon plasma coagulation (APC)
      versus surveillance endoscopy was studied. Endoscopy and histopathological
      appearances of Barrett's esophagus at 12 months follow-up was also studied.
      Initially, at least 95% ablation of the metaplastic mucosa was achieved in 25 of
      the 26 treated patients. At 12 months, 14 of 23 APC patients had at least 95%
      regression, and nine of 23 had complete regression of Barrett's esophagus. No
      surveillance patient had more than 95% regression. The length of Barrett's
      esophagus shortened significantly after APC (mean 3.0 vs. 0.5 cm). Significant
      regression of Barrett's esophagus follows ablation with APC, although complete
      regression was achieved in less than half. The role of APC ablation of non
      dysplastic Barrett's esophagus remains uncertain.

PMID- 19101799
TI  - Over-expression of EphA2 and EphrinA-1 in human gastric adenocarcinoma and its
      prognostic value for postoperative patients.
AB  - This study aims to investigate the expression and significance of EphA2 and
      EphrinA-1 in human gastric adenocarcinoma progression and prognosis. The
      expression of EphA2 and EphrinA-1 was detected in the cell lines and tissues of
      gastric adenocarcinoma. Different expression levels of EphA2 and EphrinA-1 were
      found in two cell lines. The expression of EphA2 and EphrinA-1 was significantly
      higher in gastric adenocarcinoma tissues than in normal tissues. Statistical
      analysis showed a significant correlation of EphA2 expression with the depth of
      tumor invasion, tumor-node-metastasis (TNM) stages, and lymph node metastasis.
      EphrinA-1 over-expression was significantly correlated with TNM stages and lymph
      node metastasis, while EphA2 expression was found to be an independent prognostic
      factor of postoperative gastric adenocarcinoma. In conclusion, the increased
      expression of EphA2 and EphrinA-1 plays an important role in the progression of
      human gastric adenocarcinoma, in which elevated EphA2 expression is an
      independent factor that indicates poor prognosis in postoperative gastric
      adenocarcinoma.

PMID- 19101800
TI  - Sildenafil, an inhibitor of phosphodiesterase subtype 5, prevents indomethacin
      induced small-intestinal ulceration in rats via a NO/cGMP-dependent mechanism.
AB  - We examined the effect of sildenafil, an inhibitor of phosphodiesterase subtype
      5, that catalyzes hydrolysis of 3',5'-cyclic guanosine monophosphate (cGMP), on
      indomethacin-induced small-intestinal ulceration in rats and investigated the
      mechanism of this action, especially in relation to endogenous nitric oxide (NO).
      Animals without fasting were given indomethacin (10 mg/kg) s.c. and then killed
      24 h later. Indomethacin produced hemorrhagic lesions in the small intestine,
      accompanied by a promotion of enterobacterial invasion and the expression of
      inducible NO synthase (iNOS) as well as myeloperoxidase (MPO) activity in the
      mucosa. Sildenafil (3-20 mg/kg), given p.o. 30 min before indomethacin, dose
      dependently reduced the severity of these lesions, with concomitant suppression
      of the increase in MPO activity, iNOS expression and bacterial invasion. These
      effects were attenuated by the prior administration of the nonselective NOS
      inhibitor, N (G)-nitro-L-arginine methyl ester, in an L-arginine-reversible
      manner. Indomethacin also decreased the secretion of mucus and fluid
      (enteropooling) and enhanced intestinal motility, but these responses were all
      prevented by the prior administration of sildenafil. Likewise, pretreatment of
      the animals with NOR-3, a NO donor, also reversed the functional changes caused
      by indomethacin, followed by suppression of bacterial invasion and iNOS
      expression, and prevented the development of intestinal lesions. These results
      suggest that sildenafil prevents indomethacin-induced small-intestinal ulceration
      in rats, via a NO/cGMP-dependent mechanism, and this effect is functionally
      associated with an increase in the secretion of mucus/fluid and a decrease of
      hypermotility, resulting in the suppression of bacterial invasion and iNOS
      expression following indomethacin treatment.

PMID- 19101801
TI  - A clinical overview of a retrospective study about adult intussusceptions:
      focusing on discrepancies among previous studies.
AB  - This study was to determine clinical entity of adult intussusception, focusing on
      discrepancies among previous studies and to retrospectively investigate the
      factors associated with malignancy and survival for 10 years. In our study, 3.7%
      (N=42) of intussusception were adults. The most common symptom was acute
      abdominal pain (64.3%). Enteric, ileocolic, ileocecal, and colocolic
      intussusception included 52.4, 9.5, 14.3, and 23.8% of patients, respectively.
      Two patients (9.1%) with enteric (N=22), no patient with ileocolic (N=4), three
      patients (50%) with ileocecal (N=6), and five patients (50%) with colocolic
      (N=10) intussusception were malignant. The factor associated with malignancy was
      only chronic abdominal pain without acute abdominal pain (P = 0.018) and the
      absence of fever and ileocecal intussusception were associated with survival
      (P=0.010, 0.009). In our study, the most common symptom was acute abdominal pain,
      and enteric intussusception was the most common type. The difference in clinical
      presentation and location of intussusception might have resulted from small
      number of cases or selection of cases.

PMID- 19101802
TI  - Do predictors of the implementation quality of school-based prevention programs
      differ by program type?
AB  - Research has indicated that the effectiveness of school-based prevention programs
      is affected by the implementation quality of these programs. As the importance of
      implementation has become clear, researchers have identified factors that appear
      to be related to implementation quality, including local program selection and
      training, integration into school operations, organizational capacity, principal
      support, and program standardization; however, it is unknown whether the impact
      of these factors differs by program type. Data from a nationally representative
      sample of 544 schools are used to create structural equation models representing
      hypothesized relationships among school and program factors and implementation
      quality, controlling for exogenous community factors. The relative importance of
      these factors for individual-level programs, such as behavior modification and
      counseling programs, versus environmental-level programs, such as improvements to
      classroom management or school planning and climate change programs, is the focus
      of this study. Implications for the implementation of school-based prevention
      program are discussed.

PMID- 19101803
TI  - Cardiovascular disease risks in Hmong refugees from Wat Tham Krabok, Thailand.
AB  - No epidemiological studies on cardiovascular disease (CVD) were conducted on
      Hmong refugees arriving to the U.S. from 1970s to 1990s. This study measured
      prevalence of CVD and CVD risk factors in Hmong refugees newly arriving from Wat
      Tham Krabok, Thailand 2004-2006. Cross-sectional study of 1,462 Hmong refugees
      who received refugee screening exams at seven primary care clinics in St. Paul
      MN, June 2004-March 2006. In younger age group (N = 988, 0-20 years old),
      overweight equaled 13.7%, hypertension = 8.2%, pre-hypertension = 9.6% and in a
      subset, hyperglycemia equaled 20.7% and hyperlipidemia = 13.5%. In older age
      group (N = 448, >20 years old), overweight equaled 33.4%, obese = 14.8%,
      hypertension = 16.5%, and pre-hypertension = 36.2%. In a subset, diabetes
      mellitus = 2.8%, hyperglycemia = 31.7%, hyperlipidemia = 25.8%, renal
      insufficiency = 9%, and hyperuricemia = 11.7%. Hmong refugees had significant CVD
      risk factors on arrival. Healthcare providers and public health officers must
      identify CVD in addition to infectious diseases when refugees arrive in the U.S.
      and must address long-term care in order to forestall the development of CVD.

PMID- 19101804
TI  - Reconsidering patient participation in guideline development.
AB  - Health care has become increasingly patient-centred and medical guidelines are
      considered to be one of the instruments that contribute towards making it so. We
      reviewed the literature to identify studies on this subject. Both normative and
      empirical studies were analysed. Many studies recommend active patient
      participation in the process of guideline development as the instrument to make
      guidelines more patient-centred. This is done on the assumption that active
      patient participation will enhance the quality of the guidelines. We found no
      empirical evidence, however, to support this assumption. Moreover, the studies
      show that patients experience several difficulties in the participation process,
      which cannot solely be traced back to flawed practices. Given this poor track
      record we conclude that the plea to actively involve patients in the guideline
      development process should be reconsidered.

PMID- 19101805
TI  - Effect of plasticizer on release kinetics of diclofenac sodium pellets coated
      with Eudragit RS 30 D.
AB  - The present study was designed to investigate the effect of two plasticizers,
      i.e., triethyl citrate (TEC) and polyethylene glycol 6000 (PEG 6000) on the in
      vitro release kinetics of diclofenac sodium from sustained-release pellets.
      Ammonio methacrylate copolymer type B (Eudragit RS 30 D) is used as the release
      retarding polymer. Both plasticizers were used at 10% and 15% (w/w) of Eudragit
      RS 30 D. Pellets were prepared by powder layering technology and coated with
      Eudragit RS 30 D by air suspension technique. Thermal properties of drug and drug
      loaded beads were studied using differential scanning calorimeter (DSC). DSC
      thermogram represented the identity of raw materials and exhibited no interaction
      or complexation between the active and excipients used in the pelletization
      process. Dissolution study was performed by using USP apparatus 1. No significant
      difference was observed among the physical properties of the coated pellets of
      different batches. When dissolution was performed as pure drug, about 8.22% and
      90% drug was dissolved at 2 h in 0.1 N HCl and at 30 min in buffer (pH 6.8),
      respectively. From all formulations, the release of drug in acid media was very
      negligible (maximum 1.8 +/- 0.08% at 2 h) but in buffer only 12% and 30% drug was
      released at 10 h from coated pellets containing TEC and PEG 6000, respectively,
      indicating that Eudragit RS 30 D significantly retards the drug release rate and
      that drug release was varied according to the type and amount of plasticizers
      used. The amount of TEC in coating formulation significantly effected drug
      release (p < 0.001), but the effect of PEG 6000 was not significant. Formulations
      containing PEG 6000 released more drug (98.35 +/- 2.35%) than TEC (68.01 +/-
      1.04%) after 24 h. Different kinetic models like zero order, first order, and
      Higuchi were used for fitting drug release pattern. Zero order model fitted best
      for diclofenac release in all formulations. Drug release mechanism was derived
      with Korsmeyer equation.

PMID- 19101806
TI  - Toxicity of tri- and penta-valent arsenic, alone and in combination, to the
      cladoceran Daphnia carinata: the influence of microbial transformation in natural
      waters.
AB  - The acute toxicity of arsenic(III) and arsenic(V) alone and in combination to a
      cladoceran, Daphnia carinata, was studied in both cladoceran culture medium and
      natural water collected from a local suburban stream. As(III) was found to be
      more toxic than As(V) to Daphnia survival. The LC(50) values for As(III), As(V),
      and As(III) + As(V) were 0.554, 1.499, and 0.692 mg l(-1), respectively. Although
      various species of As, particularly As(III) and As(V) co-exist together in
      natural waters, the existing guidelines for water quality are based on individual
      As species. The results of this investigation suggest that As(III) and As(V) can
      interact either synergistically or additively resulting in an increase in the
      overall toxicity of the mixture compared to individual As species. Also,
      indigenous microorganisms in natural water may play a significant role in the
      transformation of As, thereby influencing the toxicity of As in receiving waters.
      This study clearly suggests that the joint action of As species should be
      considered in the development of water quality guidelines. To our knowledge this
      is the first study on the interactive effect of As(III) and As(V) to a
      cladoceran. Thus, this study suggests that these two species of As, when present
      together above 0.1 mg l(-1) concentration, are toxic to fresh water
      invertebrates; therefore, pollution with these compounds may adversely affect
      natural ecosystems.

PMID- 19101807
TI  - Chemistry of inorganic arsenic in soils: kinetics of arsenic adsorption
      desorption.
AB  - The influence of ionic strength, index cations and competing anions on arsenate
      (As(V)) adsorption-desorption kinetics was studied in an Alfisol soil. A flow
      through reactor system similar to that developed by Carski and Sparks (Soil Sci
      Soc Am J 49:1114-1116, 1985) was constructed for the experiments. Arsenate
      adsorption kinetics for all the treatments were initially fast with 58-91% of
      As(V) adsorbed in the first 15 min. Beyond 15 min, As(V) adsorption continued at
      a slower rate for the observation period of the experiments. Changes in the
      solution composition had differing effects on the cumulative amount of As(V)
      adsorbed by the soil. Ionic strength and different index cations had little
      effect on the amount of As(V) adsorbed, while the presence of phosphate decreased
      the amount of As(V) adsorbed from 169 to 89 and 177 to 115 g As(V) microg(-1) in
      0.03 M sodium nitrate and 0.01 M calcium nitrate, respectively. Considerably less
      As(V) was desorbed than was adsorbed, with only between 2 to 17% of the adsorbed
      As(V) desorbed. The presence of phosphate increased the amount of As(V) desorbed
      by 17%, but other changes in the solution ionic strength or index cation had
      little effect on the amount of As(V) desorbed.

PMID- 19101808
TI  - The Generation R Study: design and cohort update until the age of 4 years.
AB  - The Generation R Study is a population-based prospective cohort study from fetal
      life until young adulthood. The study is designed to identify early environmental
      and genetic causes of normal and abnormal growth, development and health from
      fetal life until young adulthood. The study focuses on four primary areas of
      research: (1) growth and physical development; (2) behavioural and cognitive
      development; (3) diseases in childhood; and (4) health and healthcare for
      pregnant women and children. In total, 9,778 mothers with a delivery date from
      April 2002 until January 2006 were enrolled in the study. Of all eligible
      children at birth, 61% participate in the study. In addition, more detailed
      assessments are conducted in a subgroup of 1,232 pregnant women and their
      children. Data collection in the prenatal phase and postnatal phase until the age
      of 4 years includes questionnaires, detailed physical and ultrasound
      examinations, behavioural observations and biological samples. This paper gives
      an update of the study design and cohort profile until the children's age of 4
      years. Eventually, results forthcoming from the Generation R Study have to
      contribute to the development of strategies for optimizing health and healthcare
      for pregnant women and children.

PMID- 19101809
TI  - Effects of spirodiclofen on reproduction in a susceptible and resistant strain of
      Tetranychus urticae (Acari: Tetranychidae).
AB  - In this study the reproductive capacity of a laboratory-selected spirodiclofen
      resistant strain was investigated after treatment with spirodiclofen. Firstly,
      females were exposed to different concentrations of spirodiclofen (200 and 1,000
      mg/l) during 6, 12 or 24 h. In contrast to the susceptible parental strain, the
      fecundity and fertility of resistant mites was not affected by treatment with
      these concentrations after any time of exposure tested. Secondly, pre-treatment
      of the resistant females with the synergists PBO or DEF could increase the
      inhibitory effect of spirodiclofen on reproduction, demonstrating the possible
      involvement of monooxygenases and esterases in metabolic detoxification of the
      acaricide. Because spirodiclofen interferes with lipid biosynthesis, total lipid
      content was measured in female adults. There were no significant differences
      between treated and non-treated female adults, both in the susceptible and
      resistant strain. However, the total lipid content in the resistant females was
      significantly higher than in susceptible females. Our data shows that the
      detection of spirodiclofen resistance should not be limited to mortality
      bioassays with eggs or larvae, but should be combined with inhibitory studies on
      female fertility and fecundity.

PMID- 19101810
TI  - The impact of climate-induced distributional changes on the validity of
      biological water quality metrics.
AB  - We present data on the distributional changes within an order of
      macroinvertebrates used in biological water quality monitoring. The British
      Odonata (dragonflies and damselflies) have been shown to be expanding their range
      northwards and this could potentially affect the use of water quality metrics.
      The results show that the families of Odonata that are used in monitoring are
      shifting their ranges poleward and that species richness is increasing through
      time at most UK latitudes. These past distributional shifts have had negligible
      effects on water quality indicators. However, variation in Odonata species
      richness (particularly in species-poor regions) has a significant effect on water
      quality metrics. We conclude with a brief review of current and predicted
      responses of aquatic macroinvertebrates to environmental warming and maintain
      that caution is warranted in the use of such dynamic biological indicators.

PMID- 19101811
TI  - Assessment of trace metal pollution in surface sediments of Nemrut Bay, Aegean
      Sea.
AB  - Surface sediments collected from nine stations in Nemrut Bay, Aegean Sea were
      analyzed for trace metals (Hg, Cd, Pb, Cr, Cu, Zn, Mn, Ni, Fe, As, and Mg) and
      grain sizes. The results were compared with the numerical sediment guidelines
      used in North America as well as literature values reported for similar studies
      conducted in Izmit Bay and Izmir Bay. The metal levels were also evaluated
      according to the enrichment factor and contamination factor analyses. The
      analyses revealed significant anthropogenic pollution of Hg, Pb, Zn, and As in
      the surficial sediments of Nemrut Bay.

PMID- 19101812
TI  - Assessment and occurrence of various heavy metals in surface water of Ganga river
      around Kolkata: a study for toxicity and ecological impact.
AB  - A study was conducted during November, 2005-October, 2006 to evaluate the surface
      water quality of river Ganga around Kolkata. The samples were analyzed for a
      number of physico-chemical parameters using standard laboratory procedures and
      giving prime thrust to determine the heavy metal concentrations (Fe, Mn, Cu, Zn,
      Pb, Cd, Cr, and Ni) of surface water at four different locations of the river
      Ganga around Kolkata from two points (middle of the river stream and a discharge
      point) at each location. Out of 96 samples analyzed, Fe, Mn, Cu, Zn, and Ni were
      detected in 71, 47, 38, 60, and 45 samples in the concentrations ranging from
      0.013 to 5.49, 0.022 to 1.78, 0.003 to 0.033, 0.005 to 0.293, and 0.045 to 0.24
      mg L(-1), respectively. Cd and Pb were detected in six and 21 samples in the
      range of 0.005 to 0.006 and 0.05 to 0.53 mg L(-1), respectively. But Cr was not
      detected in any of the samples analyzed. The metals exhibited no significant
      variation with respect to sampling locations as well as discharge points.
      However, the concentration of those metals varied with season, being higher in
      rainy and lower in winter season.

PMID- 19101813
TI  - Prevalence of certain inorganic constituents in groundwater samples of Erode
      district, Tamilnadu, India, with special emphasis on fluoride, fluorosis and its
      remedial measures.
AB  - A total of 60 drinking water samples collected from Erode district, Tamilnadu,
      India were analysed for fluoride contamination, besides water quality parameters
      such as pH, electrical conductivity, total dissolved solids, total alkalinity,
      total hardness, fluoride, bicarbonates, calcium, magnesium, nitrate, sulphate,
      phosphate, sodium and potassium. The results obtained were found to exceed the
      permissible limits. The concentration of fluoride in the water samples ranged
      between 0.5 and 8.2 mg/l and revealed that 80% of the water samples contain
      fluoride above the maximum permissible limit. Similarly, the concentrations of
      nitrate, hardness, calcium and magnesium in some samples were also more than the
      permissible level. Pearson's correlation coefficient among the parameters showed
      a positive correlation of fluoride with total hardness and calcium. It is
      inferred from the study that these water sources can be used for potable purpose
      only after prior treatment.

PMID- 19101814
TI  - Surface and subsurface water quality appraisal for irrigation.
AB  - Use of irrigation water available from various sources in agriculture is
      justified on agronomic and economic grounds but care must be taken to minimize
      its adverse environmental and health impacts. During the study 44 water samples,
      available from the various resources viz., canal, sewage pipe line, tube wells in
      confined aquifers, tube wells in unconfined aquifers, and wells in the Chaka
      block district Allahabad, were chemically analyzed to check its suitability for
      irrigation and to classify it according to amount of salts present. The analysis
      reveals that most of the samples were within the lower alkalinity limit (pH 7.17
      8.42), except sewage water (pH 7.34-9.04). The electrical conductivity of the
      samples ranged from 0.26 to 1.37 millimhos/cm. Potassium, sodium, calcium, and
      phosphorus are all found to be in permissible range except one sample in the
      village Kuria in which Na percentage was found in doubtful category. The other
      parameters like sodium adsorption ratio, SAR (1.17-2.74), residual sodium
      carbonate, RSC (-4.46 to -1.07), and soluble sodium percentage, SSP (63.97-28.15)
      were also found below the permissible limit.

PMID- 19101815
TI  - Basal medium composition and serum or serum replacement concentration influences
      on the maintenance of murine embryonic stem cells.
AB  - The expansion of stem cell numbers while retaining their developmental properties
      is a bioprocess challenge. We compared the growth rates and embryoid body (EB)
      formation yields of R1 and EFC murine embryonic stem cells (mESC) cultured in two
      basal media (DMEM or DMEM:F12) with additions of 1.7-15% fetal bovine serum (FBS)
      or serum replacer (KOSR). Whereas the basal medium or KOSR dose did not have a
      significant effect on growth rate for either cell line, increasing doses of KOSR
      had a significant negative effect on the EB yield of EFC cells. Use of DMEM:F12
      and increasing doses of FBS independently and significantly increased the growth
      rate for both cell lines. DMEM:F12 also significantly increased EB yields for
      both cell lines. The results show that use of DMEM:F12 and several-fold lower
      than conventional concentrations of KOSR can efficiently support maintenance of
      mESC and that KOSR should be dose as well as lot optimized.

PMID- 19101816
TI  - Integrated resource-driven pig production systems in a mountainous area of
      Northeast India: production practices and pig performance.
AB  - Data on pig production system was derived through structured household interviews
      from a total number of 320 rural households and performance of pigs was assessed.
      Results revealed that the pig production system represented mixed farming based
      mainly on the common property resources. Majority of the pigs were reared in
      intensive system and fed with home made cooked feed (kitchen waste and locally
      available plants). The body weight of crossbred, Burmese and local pigs were 67,
      65.4 and 45.6 kg, respectively at 12 months of age with average daily body weight
      of 184, 179 and 125 g, respectively. The overall mortality among the pigs was
      17.96%. The major causes of mortality in pigs were Swine fever, Swine erysipelas,
      digestive disorders, nephritis and respiratory disorders. The body weight gain in
      pigs subjected to deworming and mineral mixture supplementation (218 g/day) was
      significantly (p < 0.05) higher than the control group (178 g/day). The input
      output ratio was 1:1.7 for both crossbred and Burmese pigs, while the
      corresponding ratio for local pigs was 1:1.2. It is inferred that the smallholder
      resource driven pig production system is economically viable and sustainable at
      household level and there is enough scope to improve the smallholder resource
      driven pig production system.

PMID- 19101817
TI  - Genotyping of benzimidazole susceptible and resistant alleles in different
      populations of Haemonchus contortus from Himalayan and sub-Himalayan regions of
      North-West India.
AB  - An allele-specific PCR was standardized to diagnose the mutation (Phe to Try) at
      residue 200 of the isotype 1 beta tubulin gene responsible for benzimidazole
      resistance in Haemonchus contortus adult and infective larvae. Adult and
      infective larvae of Haemonchus contortus were collected from sheep under
      different managemental practices (intensive and extensive) in temperate Himalayan
      regions (Mukteshwar and Kedarkhatta), sub-himalayan region (Pantnagar) of
      Uttarakhand state and subtropical region of Uttar Pradesh (Bareilly) in north
      west India. Genotyping of adult H. contortus, collected from abomasi of
      slaughtered sheep reared under extensive management, by AS-PCR revealed that the
      frequency of resistant (r) alleles was significantly higher (P < 0.001) at
      Pantnagar (0.57) as compared to Bareilly (0.25) and Mukteshwar (0.08). Also,
      genotyping of infective larvae of the parasite from intensively managed sheep
      farms indicated that the frequency of resistant (r) alleles was significantly
      higher (P < 0.001) at Pantnagar (0.85) as compared to Kedarkattha (0.70) and
      Bareilly (0.62). The results revealed that managemental practices followed in the
      areas under study have a direct bearing on the spread of benzimidazole resistant
      alleles.

PMID- 19101818
TI  - Gender issues in livestock production: a case study of Zimbabwe.
AB  - The importance of main streaming gender issues in development programmes is now
      recognized by governments and development agents. This paper evaluates the role
      of gender in smallholder livestock production using Zimbabwe as a case study. It
      draws on several studies and assesses the gender dimension in terms of access and
      control, decision making and, division of labour. It is shown that for mainly
      traditional and historical reasons men continue to dominate livestock production
      although the situation is gradually changing. Men eclipse women in terms of
      ownership of more valuable stock, the making of decisions and the control of
      livestock production. This suggests that gender is important in livestock
      production and must be considered among other factors. The complexity of the
      system is noted but more gender disaggregated quantitative data is required if
      gender is to be effectively mainstreamed in livestock development programmes.

PMID- 19101819
TI  - H(2)O(2) increases de novo synthesis of (6R)-L-erythro-5,6,7,8
      tetrahydrobiopterin via GTP cyclohydrolase I and its feedback regulatory protein
      in vitiligo.
AB  - Patients with vitiligo accumulate up to 10(-3) mol/L concentrations of H(2)O(2)
      in their epidermis, which in turn affects many metabolic pathways in this
      compartment, including the synthesis and recycling of the cofactor (6R)-L-erythro
      5,6,7,8-tetrahydrobiopterin (6BH(4)). De novo synthesis of 6BH(4) is dependent on
      the rate-limiting enzyme GTP cyclohydrolase I (GTPCHI) together with its feedback
      regulatory protein (GFRP). This step is controlled by 6BH(4) and the essential
      amino acid L-phenylalanine. In the study presented here we wanted to investigate
      whether H(2)O(2) affects the GTPCHI/GFRP cascade in these patients. Our results
      demonstrated concentration-dependent regulation of rhGTPCHI where 100 micromol/L
      H(2)O(2) was the optimum concentration for the activation of the enzyme and >300
      micromol/L resulted in a decrease in activity. Oxidation of GFRP and GTPCHI does
      not affect feedback regulation via L-phenylalanine and 6BH(4). In vitiligo a
      constant upregulation of 6BH(4) de novo synthesis results from epidermal build up
      of L-phenylalanine that is not controlled by H(2)O(2). Taking the results
      together, 6BH(4) de novo synthesis is controlled by H(2)O(2) in a concentration
      dependent manner, but H(2)O(2)-mediated oxidation does not affect the
      functionality of the GTPCHI/GFRP complex.

PMID- 19101820
TI  - Determination of optimal viewing regions for X-ray coronary angiography based on
      a quantitative analysis of 3D reconstructed models.
AB  - Current expert-recommended views for coronary angiography are based on heuristic
      experience and have not been scientifically studied. We sought to identify
      optimal viewing regions for first and second order vessel segments of the
      coronary arteries that provide optimal diagnostic value in terms of minimizing
      vessel foreshortening and overlap. Using orthogonal 2D images of the coronary
      tree, 3D models were created from which patient-specific optimal view maps (OVM)
      allowing quantitative assessment of vessel foreshortening and overlap were
      generated. Using a novel methodology that averages 3D-based optimal projection
      geometries, a universal OVM was created for each individual coronary vessel
      segment that minimized both vessel foreshortening and overlap. A universal OVM
      model for each coronary segment was generated based on data from 137 patients
      undergoing coronary angiography. We identified viewing regions for each vessel
      segment achieving a mean vessel foreshortening value of 5.8 +/- 3.9% for the left
      coronary artery (LCA) and 5.6 +/- 3.6% for the right coronary artery (RCA). The
      overall mean overlap values achieved were 8.7 +/- 7.9% for the LCA and 4.6 +/-
      3.2% for the RCA. This scientifically-based OVM evaluation of coronary vessel
      segments provides the means to facilitate acquisitions during coronary
      angiography and interventions that minimize imaging inaccuracies related to
      foreshortening and overlap, improving the accuracy, efficiency, and safety of
      diagnostic and interventional coronary procedures.

PMID- 19101821
TI  - cDNA, genomic sequence cloning and overexpression of ribosomal protein S25 gene
      (RPS25) from the Giant Panda.
AB  - RPS25 is a component of the 40S small ribosomal subunit encoded by RPS25 gene,
      which is specific to eukaryotes. Studies in reference to RPS25 gene from animals
      were handful. The Giant Panda (Ailuropoda melanoleuca), known as a "living
      fossil", are increasingly concerned by the world community. Studies on RPS25 of
      the Giant Panda could provide scientific data for inquiring into the hereditary
      traits of the gene and formulating the protective strategy for the Giant Panda.
      The cDNA of the RPS25 cloned from Giant Panda is 436 bp in size, containing an
      open reading frame of 378 bp encoding 125 amino acids. The length of the genomic
      sequence is 1,992 bp, which was found to possess four exons and three introns.
      Alignment analysis indicated that the nucleotide sequence of the coding sequence
      shows a high homology to those of Homo sapiens, Bos taurus, Mus musculus and
      Rattus norvegicus as determined by Blast analysis, 92.6, 94.4, 89.2 and 91.5%,
      respectively. Primary structure analysis revealed that the molecular weight of
      the putative RPS25 protein is 13.7421 kDa with a theoretical pI 10.12. Topology
      prediction showed there is one N-glycosylation site, one cAMP and cGMP-dependent
      protein kinase phosphorylation site, two Protein kinase C phosphorylation sites
      and one Tyrosine kinase phosphorylation site in the RPS25 protein of the Giant
      Panda. The RPS25 gene was overexpressed in E. coli BL21 and Western Blotting of
      the RPS25 protein was also done. The results indicated that the RPS25 gene can be
      really expressed in E. coli and the RPS25 protein fusioned with the N-terminally
      his-tagged form gave rise to the accumulation of an expected 17.4 kDa
      polypeptide. The cDNA and the genomic sequence of RPS25 were cloned successfully
      for the first time from the Giant Panda using RT-PCR technology and Touchdown
      PCR, respectively, which were both sequenced and analyzed preliminarily; then the
      cDNA of the RPS25 gene was overexpressed in E. coli BL21 and immunoblotted, which
      is the first report on the RPS25 gene from the Giant Panda. The data will enrich
      and supplement the information about RPS25, which will contribute to the
      protection for gene resources and the discussion of the genetic polymorphism.

PMID- 19101822
TI  - Lifeworld-led healthcare is more than patient-led care: an existential view of
      well-being.
AB  - In this paper we offer an appreciation and critique of patient-led care as
      expressed in current policy and practice. We argue that current patient-led
      approaches hinder a focus on a deeper understanding of what patient-led care
      could be. Our critique focuses on how the consumerist/citizenship emphasis in
      current patient-led care obscures attention from a more fundamental challenge to
      conceptualise an alternative philosophically informed framework from where care
      can be led. We thus present an alternative interpretation of patient-led care
      that we call 'lifeworld-led care', and argue that such lifeworld-led care is more
      than the general understanding of patient-led care. Although the philosophical
      roots of our alternative conceptualisation are not new, we believe that it is
      timely to re-consider some of the implications of these perspectives within
      current discourses of patient-centred policies and practice. The
      conceptualisation of lifeworld-led care that we develop includes an articulation
      of three dimensions: a philosophy of the person, a view of well-being and not
      just illness, and a philosophy of care that is consistent with this. We conclude
      that the existential view of well-being that we offer is pivotal to lifeworld-led
      care in that it provides a direction for care and practice that is intrinsically
      and positively health focused in its broadest and most substantial sense.

PMID- 19101824
TI  - Homozygosity of MSH2 c.1906G-->C germline mutation is associated with childhood
      colon cancer, astrocytoma and signs of Neurofibromatosis type I.
AB  - Hereditary non-polyposis colorectal cancer is a cancer predisposition syndrome
      known to be caused by heterozygous germline mutations in DNA mismatch repair
      genes (MMR) most commonly hMLH1, hMSH2, hMSH6. Heterozygous mutations in one of
      these genes confer an increased risk, mainly for colon and endometrial cancer.
      Recently, several publications identified that biallelic mutations in the MMR
      genes are associated with a more severe phenotype, including childhood
      malignancies and signs of neurofibromatosis type I (NF1). We report on a non
      consanguineous Ashkenazi Jewish family with two affected siblings with features
      of NF1, colon cancer and astrocytoma at age 13 and 14. Their mother developed
      endometrial cancer at age 54. Their father had leukoplakia of the vocal cords
      with a family history of pancreatic cancer. Molecular and pathology studies were
      done on the tumor tissue and on genomic DNA of family members. Tumor testing
      demonstrated a high degree of microsatellite instability (MSI analysis),
      expression of MLH1 and absence of expression of both MSH2 and MSH6 proteins. A
      biallelic c.1906G > C (p.A636P) mutation in the hMSH2 gene was detected in the
      blood of one affected child. Parental genetic testing showed that each parent was
      heterozygote for the mutation. The c.1906G > C mutation is a founder mutation in
      the Ashkenazi Jewish population. To our knowledge this is the first report of
      homozygosity for this founder mutation.

PMID- 19101823
TI  - NMR and X-RAY structures of human E2-like ubiquitin-fold modifier conjugating
      enzyme 1 (UFC1) reveal structural and functional conservation in the metazoan
      UFM1-UBA5-UFC1 ubiquination pathway.
AB  - For cell regulation, E2-like ubiquitin-fold modifier conjugating enzyme 1 (Ufc1)
      is involved in the transfer of ubiquitin-fold modifier 1 (Ufm1), a ubiquitin like
      protein which is activated by E1-like enzyme Uba5, to various target proteins.
      Thereby, Ufc1 participates in the very recently discovered Ufm1-Uba5-Ufc1
      ubiquination pathway which is found in metazoan organisms. The structure of human
      Ufc1 was solved by using both NMR spectroscopy and X-ray crystallography. The
      complementary insights obtained with the two techniques provided a unique basis
      for understanding the function of Ufc1 at atomic resolution. The Ufc1 structure
      consists of the catalytic core domain conserved in all E2-like enzymes and an
      additional N-terminal helix. The active site Cys(116), which forms a thio-ester
      bond with Ufm1, is located in a flexible loop that is highly solvent accessible.
      Based on the Ufc1 and Ufm1 NMR structures, a model could be derived for the Ufc1
      Ufm1 complex in which the C-terminal Gly(83) of Ufm1 may well form the expected
      thio-ester with Cys(116), suggesting that Ufm1-Ufc1 functions as described for
      other E1-E2-E3 machineries. alpha-helix 1 of Ufc1 adopts different conformations
      in the crystal and in solution, suggesting that this helix plays a key role to
      mediate specificity.

PMID- 19101826
TI  - A silver-staining cDNA-AFLP protocol suitable for transcript profiling in the
      latex of Hevea brasiliensis (para rubber tree).
AB  - cDNA amplified fragment length polymorphism (cDNA-AFLP) is a powerful transcript
      profiling tool widely used in diverse plant species. When applied to a new
      biological system, however, existing protocols usually require substantial
      modifications. Furthermore, the usage of radioactive isotope in typical protocols
      excludes their application in many labs. Latex, as the cytoplasm of rubber
      producing cells sees a critical role in elucidating rubber biosynthesis and its
      regulation in rubber tree (Hevea brasiliensis). This paper describes a detailed
      step-by-step silver-staining cDNA-AFLP procedure, which is suitable to latex
      transcript profiling analysis. Theoretical analysis revealed that with the
      combination of two restriction enzyme pairs (ApoI/MseI and TaqI/MseI),
      approximately 94% of latex whole transcriptome could be visualized. After varying
      multiple parameters, including the amounts of primary and secondary template
      usage, pre-amplification cycle number and gel development, we obtained a high
      quality silver-staining fingerprint. In the ApoI/MseI system, an average of 88.6
      discernable bands (100-1,000 bp) was produced for each selective primer pair, and
      97.2 bands for another system (TaqI/MseI). TaqI/MseI was the first pair of 4-bp
      cutters used in cDNA-AFLP analysis and proved to be efficient and reliable. The
      sensitivity and reliability of our method were further verified by an application
      example in detecting differential gene expression in the latex of Hevea tree.

PMID- 19101827
TI  - Role of in silico tools in gene discovery.
AB  - Common complex diseases remain a major health challenge and involve the
      interaction of multiple genes and environmental factors. Discovering the relevant
      genes is difficult although it is known that disease risk can originate from the
      variation of an individual's genome. Application of in silico tools can
      significantly improve the detection of genes and variation. Data mining and
      automated tracking of new knowledge facilitate locus mapping. At the gene search
      stage, in silico prioritization of candidate genes plays an indispensable role in
      dealing with linked or associated loci. In silico analysis can also differentiate
      subtle consequences of coding DNA variants and remains the major tool to predict
      potential effects of non-coding DNA variants on gene transcription and/or pre
      mRNA splicing.

PMID- 19101828
TI  - Severe hyponatremia caused by hyperglycaemia due to interferon alpha therapy in
      advanced renal cell carcinoma.

PMID- 19101829
TI  - Impact of oxygenation of bioartificial liver using perfluorocarbon emulsion
      perftoran on metabolism of human hepatoma C3A cells.
AB  - One of the most important challenges in bioartificial liver designed for patients
      suffering from acute liver failure is oxygenation of cells within the bioreactor.
      The aim of this study was to evaluate the impact of oxygenation of bioartificial
      liver using perfluorocarbon (PFC) emulsion on the metabolic activity of hepatic
      cells in vitro. Mineral fibers coated with collagen type I were used as scaffolds
      for hepatic cells. Significantly higher total protein synthesis by hepatic C3A
      cells cultured in the bioreactor for 24 hours, in the group treated with medium
      supplemented with PFC emulsion, was observed in comparison with medium without
      PFC. Albumin production increased in the group treated with PFC after 1 hour of
      perfusion and was continuously, statistically, significantly higher during
      perfusion then the control group. In conclusion, the use of oxygen carriers, such
      as the PFC emulsion, can significantly improve synthetic performance of the
      bioreactor. Mineral fibers coated with extracellular proteins may serve as
      support for hepatic cells in the bioreactor.

PMID- 19101832
TI  - Final amended report on the safety assessment of Methylparaben, Ethylparaben,
      Propylparaben, Isopropylparaben, Butylparaben, Isobutylparaben, and Benzylparaben
      as used in cosmetic products.
AB  - Parabens is the name given to a group of p-hydroxybenzoic acid (PHBA) esters used
      in over 22,000 cosmetics as preservatives at concentrations up to 0.8% (mixtures
      of parabens) or up to 0.4% (single paraben). The group includes Methylparaben,
      Ethylparaben, Propylparaben, Isopropylparaben, Butylparaben, Isobutylparaben, and
      Benzylparaben. Industry estimates of the daily use of cosmetic products that may
      contain parabens were 17.76 g for adults and 378 mg for infants. Parabens in
      cosmetic formulations applied to skin penetrate the stratum corneum in inverse
      relation to the ester chain length. Carboxylesterases hydrolyze parabens in the
      skin. Parabens do not accumulate in the body. Serum concentrations of parabens,
      even after intravenous administration, quickly decline and remain low. Acute
      toxicity studies in animals indicate that parabens are not significantly toxic by
      various routes of administration. Subchronic and chronic oral studies indicate
      that parabens are practically nontoxic. Numerous genotoxicity studies, including
      Ames testing, dominant lethal assay, host-mediated assay, and cytogenic assays,
      indicate that the Parabens are generally nonmutagenic, although Ethylparaben and
      Methylparaben did increase chromosomal aberrations in a Chinese Hamster ovary
      cell assay. Ethylparaben, Propylparaben, and Butylparaben in the diet produced
      cell proliferation in the forestomach of rats, with the activity directly related
      to chain length of the alkyl chain, but Isobutylparaben and Butylparaben were
      noncarcinogenic in a mouse chronic feeding study. Methylparaben was
      noncarcinogenic when injected subcutaneously in mice or rats, or when
      administered intravaginally in rats, and was not cocarcinogenic when injected
      subcutaneously in mice. Propylparaben was noncarcinogenic in a study of
      transplacental carcinogenesis. Methylparaben was nonteratogenic in rabbits, rats,
      mice, and hamsters, and Ethylparaben was nonteratogenic in rats. Parabens, even
      at levels that produce maternal toxicity, do not produce fetal anomalies in
      animal studies. Parabens have been extensively studied to evaluate male
      reproductive toxicity. In one in vitro study, sperm were not viabile at
      concentrations as low as 6 mg/ml Methylparaben, 8 mg/ml Ethylparaben, 3 mg/ml
      Propylparaben, or 1 mg/ml Butylparaben, but an in vivo study of 0.1% or 1.0%
      Methylparaben or Ethylparaben in the diet of mice reported no spermatotoxic
      effects. Propylparaben did affect sperm counts at all levels from 0.01% to 1.0%.
      Epididymis and seminal vesicle weight decreases were reported in rats given a 1%
      oral Butylparaben dose; and decreased sperm number and motile activity in F(1)
      offspring of rats maternally exposed to 100 mg/kg day(- 1) were reported.
      Decreased sperm numbers and activity were reported in F(1) offspring of female
      rats given Butylparaben (in DMSO) by subcutaneous injection at 100 or 200 mg/kg
      day(- 1), but there were no abnormalities in the reproductive organs.
      Methylparaben was studied using rats at levels in the diet up to an estimated
      mean dose of 1141.1 mg/kg day(- 1) with no adverse testicular effects.
      Butylparaben was studied using rats at levels in the diet up to an estimated mean
      dose of 1087.6 mg/kg day(- 1) in a repeat of the study noted above, but using a
      larger number of animals and a staging analysis of testicular effects-no adverse
      reproductive effects were found. Butylparaben does bind to estrogen receptors in
      isolated rat uteri, but with an affinity orders of magnitude less than natural
      estradiol. Relative binding (diethylstilbesterol binding affinity set at 100) to
      the human estrogen receptors alpha and beta increases as a function of chain
      length from not detectable for Methylparaben to 0.267 +/- 0.027 for human
      estrogen receptor alpha and 0.340 +/- 0.031 for human estrogen receptor beta for
      Isobutylparaben. In a study of androgen receptor binding, Propylparaben exhibited
      weak competitive binding, but Methylparaben had no binding effect at all. PHBA at
      5 mg/kg day(-1) subcutaneously (s.c.) was reported to produce an estrogenic
      response in one uterotrophic assay using mice, but there was no response in
      another study using rats (s.c. up to 5 mg/kg day(- 1)) and mice (s.c. up to 100
      mg/kg day(- 1)) and in a study using rats (s.c. up to 100 mg/kg day(- 1)).
      Methylparaben failed to produce any effect in uterotrophic assays in two
      laboratories, but did produce an effect in other studies from another laboratory.
      The potency of Methylparaben was at least 1000x less when compared to natural
      estradiol. The same pattern was reported for Ethylparaben, Propylparaben, and
      Butylparaben when potency was compared to natural estradiol. In two studies,
      Isobutylparaben did produce an estrogenic response in the uterotrophic assay, but
      the potency was at least 240,000x less than estradiol. In one study,
      Benzylparaben produced an estrogenic response in the uterotrophic assay, but the
      potency was at least 330,000x less than estradiol. Estrogenic activity of
      parabens and PHBA was increased in human breast cancer cells in vitro, but the
      increases were around 4 orders of magnitude less than that produced by estradiol.
      Parabens are practically nonirritating and nonsensitizing in the population with
      normal skin. Paraben sensitization has occurred and continues to be reported in
      the case literature, but principally when exposure involves damaged or broken
      skin. Even when patients with chronic dermatitis are patch-tested to a parabens
      mix, parabens generally induce sensitization in less than 4% of such individuals.
      Many patients sensitized to paraben-containing medications can wear cosmetics
      containing these ingredients with no adverse effects. Clinical patch testing data
      available over the past 20 years demonstrate no significant change in the overall
      portion of dermatitis patients that test positive for parabens. As reviewed by
      the Cosmetic Ingredient Review (CIR) Expert Panel, the available acute,
      subchronic, and chronic toxicity tests, using a range of exposure routes,
      demonstrate a low order of parabens' toxicity at concentrations that would be
      used in cosmetics. Parabens are rarely irritating or sensitizing to normal human
      skin at concentrations used in cosmetics. Although parabens do penetrate the
      stratum corneum, metabolism of parabens takes place within viable skin, which is
      likely to result in only 1% unmetabolized parabens available for absorption into
      the body. The Expert Panel did consider data in the category of endocrine
      disruption, including male reproductive toxicity and various estrogenic activity
      studies. The CIR Expert Panel compared exposures to parabens resulting from use
      of cosmetic products to a no observed adverse effect level (NOAEL) of 1000 mg/kg
      day(- 1) based on the most statistically powerful and well-conducted study of the
      effects of Butylparabens on the male reproductive system. The CIR Expert Panel
      considered exposures to cosmetic products containing a single parabens
      preservative (use level of 0.4%) separately from products containing multiple
      parabens (use level of 0.8%) and infant exposures separately from adult exposures
      in determining margins of safety (MOS). The MOS for infants ranged from
      approximately 6000 for single paraben products to approximately 3000 for multiple
      paraben products. The MOS for adults ranged from 1690 for single paraben products
      to 840 for multiple paraben products. The Expert Panel considers that these MOS
      determinations are conservative and likely represent an overestimate of the
      possibility of an adverse effect (e.g., use concentrations may be lower,
      penetration may be less) and support the safety of cosmetic products in which
      parabens preservatives are used.

PMID- 19101833
TI  - Final report of the cosmetic ingredient review expert panel on the safety
      assessment of Polyisobutene and Hydrogenated Polyisobutene as used in cosmetics.
AB  - Polyisobutene and Hydrogenated Polyisobutene are homopolymers of isobutene. These
      ingredients are produced in a wide range of molecular weights. Polybutene is a
      chemically related cosmetic ingredient previously determined to be safe as used
      in cosmetic products. Polyisobutene is used in cosmetic products as a binder,
      film former, and nonaqueous viscosity-increasing agent. Hydrogenated
      Polyisobutene functions as a skin-conditioning agent-emollient and nonaqueous
      viscosity-increasing agent with a wide range of uses in cosmetic formulations.
      The estimated octanol water partition coefficient for Hydrogenated Polyisobutene
      and Polybutene is log K(ow) of 13.27 and the estimated water solubility was 5.6 x
      10(-3) ng/L for Hydrogenated Polyisobutene and Polybutene. Acute oral toxicity
      testing demonstrated no effects other than lethargy in one rat study. The oral
      LD(50) was > 5.0 g/kg in rats. No short-term or subchronic animal toxicity data
      were available. A 2-year chronic oral toxicity study of Polybutene revealed no
      gross or microscopic pathological changes, and no changes in body weights or food
      consumption, hematological results, urology, or tumor formation that could be
      correlated with Polybutene ingestion, except that in the 20,000 ppm group, three
      out of six males that died between weeks 17 and 24 exhibited hematuria. In a 2
      year chronic oral toxicity study of Polybutene in Beagle dogs, no abnormalities
      in body weight, food consumption, survival, behavioral patterns, hematology,
      blood chemistry, urinalysis, liver function, gross and histopathologic
      examinations, or organ weights and ratios were reported. In a three-generation
      reproductive study in Charles River albino rats that ingested Polybutene, none of
      the animals in successive generations differed from controls with regard to
      weight gain, litter size, the number of stillborn, and the number of viable pups
      during lactation. The survival, body weights, and reactions of test animals were
      comparable to those of controls. Neither Polyisobutene nor Hydrogenated
      Polyisobutene were ocular irritants, nor were they dermal irritants or
      sensitizers. Polyisobutene was not comedogenic in a rabbit ear study.
      Polyisobutene did not induce transformation in the Syrian hamster embryo (SHE)
      cell transformation assay, but did enhance 3-methylcholanthrene-induced
      transformation of C3H/10T1/2 cells. In a carcinogenicity study in mice,
      Polyisobutene was not carcinogenic, nor did it promote the carcinogenicity of
      7,12-dimethylbenz(alpha)anthracene. Clinical patch tests uncovered no evidence of
      dermal irritation and repeat-insult patch tests with a product containing 4%
      Hydrogenated Polyisobutene or 1.44% Hydrogenated Polyisobutene found no reactions
      greater than slight erythema. These products also were not phototoxic or
      photoallergenic. The product containing 4% Hydrogenated Polyisobutene was not an
      ocular irritant in a clinical test. The Cosmetic Ingredient Review (CIR) Expert
      Panel recognized that there are data gaps regarding use and concentration of
      these ingredients. However, the overall information available on the types of
      products in which these ingredients are used and at what concentrations indicate
      a pattern of use, which was considered by the Expert Panel in assessing safety.
      Although there is an absence of dermal absorption data for Polyisobutene and
      Hydrogenated Polyisobutene, the available octanol water partition coefficient
      data and the low solubility in water suggest very slow absorption, so additional
      data are not needed. Gastrointestinal absorption is also not a major concern due
      to the low solubility of these chemicals. Although one in vitro study did report
      that Polyisobutene did promote cellular transformation, a mouse study did not
      find evidence of tumor promotion. Because lifetime exposure studies using rats
      and dogs exposed to Polybutene failed to demonstrate any carcinogenic or tumor
      promotion effect, and a three-generation reproductive/developmental toxicity
      study produced no adverse effects, the CIR Expert Panel does not believe these
      large, mostly insoluble polymers present any risks in the practices of use and
      concentration as described in this safety assessment.

PMID- 19101834
TI  - Final report on the safety assessment of Trichloroethane.
AB  - Trichloroethane functions in cosmetics as a solvent. Although Trichloroethane has
      been reported to the Food and Drug Administration (FDA) to be used in cosmetic
      products, an industry survey found that it is not in current use in the cosmetic
      industry. Trichloroethane is considered a Class I ozone-depleting substance by
      the Environmental Protection Agency (EPA) and its use is prohibited in the United
      States, unless considered essential. The FDA has stated that Trichloroethane's
      use in cosmetics is considered nonessential. Trichloroethane is detected by gas
      chromatography, gas chromatography-mass spectrometry, and gas-liquid
      chromatography. In rats, Trichloroethane, whether inhaled or injected, is mostly
      expelled intact from the body through exhalation. A very small percentage is
      excreted in the urine. In humans, Trichloroethane is rapidly absorbed through the
      skin and eliminated in exhaled air and a very small percentage is excreted in
      urine. Inhaled Trichloroethane is eliminated in exhaled air. Acute oral LD(50)
      values have been reported as follows: 12.3 g/kg in male rats; 10.3 g/kg in female
      rats; 11.24 g/kg in female mice; 5.66 g/kg in female rabbits; and 9.47 g/kg in
      male guinea pigs. Acute toxicity studies using other routes of exposure,
      including subcutaneous injection and inhalation, produced no evidence of
      significant toxicity, except at very high exposure levels. Continuous inhalation
      exposure of rabbits to 750 mg/m(3) for 90 days did not produce any signs of
      toxicity. Continuous exposure of rats, guinea pigs, rabbits, and monkeys to 500
      ppm Trichloroethane for 6 months did not produce any signs of toxicity. Other
      short-term and subchronic inhalation exposures confirmed acute and short-term
      exposure findings that the toxic effects of inhalation were a function of both
      concentration and time. Rats receiving 750 or 1500 mg/kg day(- 1) Trichloroethane
      in corn oil by oral gavage 5 days per week for 78 weeks had reduced body weights
      and early mortality. Reduced body weights, decreased survival rates, and early
      mortality (in females) were found in mice dosed with 3000 or 6000 mg/kg day(- 1)
      (over the last 58 weeks; lower doses were administered for the first 20 weeks).
      Mice exposed to prolonged periods of Trichloroethane in an inhalation chamber had
      increased motor activity at levels up to 5000 ppm. Further increase of
      concentration of exposure resulted in less of an increase of motor activity until
      motor activity began to fall below normal at 10,000 ppm. Adverse effects on motor
      activity in rats were seen at exposures as low as 3000 ppm for 4 h. Rabbits had
      slight reddening and scaling after 10 24-h applications to abdominal skin of
      Trichloroethane mixed with 2.4% to 3.0% dioxane, and slight to moderate erythema,
      slight edema, and slight exfoliation was observed when 75% Trichloroethane and
      25% tetrachloroethylene were applied to rabbit ears for 11 days. Undiluted
      Trichloroethane applied to the clipped backs of guinea pigs produced
      histopathologic damage in the epidermis. A primary irritation index of 5.22 (out
      of 8) was reported in rabbits. Trichloroethane applied to the eyes of rabbits
      resulted in transient irritation and apparent pain, but no corneal damage. There
      was no effect on gestation, pup survival, or growth in mice given Trichloroethane
      in drinking water at up to 5.83 mg/ml during mating and/or gestation. Rats
      exhibited no or minimal effects of ingestion of Trichloroethane up to 30 ppm in
      drinking water during mating and/or gestation. There was no effect on gestation,
      pup survival, or growth in mice or rats inhaling 875 ppm Trichloroethane.
      However, prenatal exposure of rodents to Trichloroethane can produce
      developmental toxicity in the form of delayed development in the offspring.
      Trichloroethane has been found to be mutagenic in the Ames assay in some studies
      and not mutagenic in others. Trichloroethane induced transformations in Fischer
      rat embryo cell system at 99 mu M, was not mutagenic using the mouse lymphoma
      assay at up to 0.51 mu g/ml, was equivocal in that assay when tested with S9, and
      was also equivocal in a sister-chromatid exchange assay using Chinese hamster
      ovarian (CHO) cells with and without S9. Mice ingesting 80,000 ppm
      Trichloroethane in their drinking water had an increase in the frequency of
      micronucleated normochromatic erythrocytes. A peripheral blood micronucleus test
      in female mice was negative. Trichloroethane was not carcinogenic to rats when
      administered 1500 mg/kg by oral gavage 5 days/week for 78 weeks or in mice
      administered 6000 mg/kg. Exposure to 1500 ppm Trichloroethane vapor for 6 h/day,
      5 days/week for 2 years likewise gave no indications of oncogenic effects in rats
      or mice. People who have been exposed to Trichloroethane have reported dizziness,
      lassitude, unconsciousness, respiratory depression, peripheral vascular collapse,
      impaired postural control, mild encephalopathy, perioral tingling, burning on the
      tongue and discomfort in the hands and feet. The Cosmetic Ingredient Review (CIR)
      Expert Panel recognizes that Trichloroethane (1,1,1-Trichloroethane) has been
      declared a Class I ozone-depleting substance by the EPA and its use is limited to
      essential products. The FDA has determined that use of Trichloroethane in aerosol
      cosmetic products is considered nonessential. At issue for this assessment is the
      safety of direct exposure to individuals as a result of exposure to cosmetic
      products that may contain Trichloroethane. The Expert Panel found the available
      data to be sufficient to support the safety of Trichloroethane as a solvent in
      cosmetic products.

PMID- 19101835
TI  - Intoxicated fly brains: neurons mediating ethanol-induced behaviors.
AB  - In free nature, animals rarely become alcoholics. Only when humans interfere do
      they develop some aspects of dependence. In humans, it is thought that 40-60% of
      the risk to become an alcoholic is influenced by genetic factors. The interplay
      between the genetic predisposition and the environment is thought to promote
      addictive behaviors to ethanol (Schuckit, 2000). Animal models are widely used to
      functionally dissect behaviors that are associated with alcohol dependence and to
      characterize the related ethanol responsive genes (Lovinger & Crabbe, 2005).
      Thus, brain regions and neurons have been identified that mediate ethanol-induced
      behaviors (Rothenfluh & Heberlein, 2002). This review aims to give an overview of
      ethanol-induced behaviors and the correlating neurons/neuronal structures in
      Drosophila melanogaster mediating these behaviors and discusses the possible
      significance of these results.

PMID- 19101837
TI  - In vitro activities of isavuconazole against opportunistic filamentous and
      dimorphic fungi.
AB  - The in vitro activity of isavuconazole was compared to those of amphotericin B,
      fluconazole, itraconazole, voriconazole, posaconazole, and ravuconazole against
      300 clinical isolates of Pseudallescheria boydii, Paecilomyces lilacinus,
      Fusarium spp., Bipolaris spicifera, Curvularia lunata, Alternaria alternata,
      Exophiala spp., Rhizopus arrhizus, Mucor circillenoides, Absidia corymbifera,
      Blastomyces dermatitidis, Histoplasma capsulatum and Coccidioides posadasii. MICs
      were determined by a broth macrodilution method based on the CLSI M38-A
      procedure. The triazoles were relatively uniform in that they showed strong in
      vitro inhibitory activity against most of the tested fungi. In vitro activity was
      variable with strains of P. lilacinus while with Fusarium spp., the triazoles
      were found to have limited in vitro activity and amphotericin B was moderately
      active. The results suggest that isavuconazole is a broad-spectrum antifungal
      agent, effective against a wide range of moulds in vitro.

PMID- 19101836
TI  - Role of rut adenylyl cyclase in the ensemble regulation of presynaptic terminal
      excitability: reduced synaptic strength and precision in a Drosophila memory
      mutant.
AB  - Although modulation of presynaptic terminal excitability can profoundly affect
      transmission efficacy, how excitability along axonal terminal branches is
      regulated requires further investigations. We performed focal patch recording in
      Drosophila larval neuromuscular junctions (NMJs) to monitor the activity of
      individual synaptic boutons along the presynaptic terminal. Analysis of the
      learning mutant rutabaga (rut) suggests a tight regulation of presynaptic
      terminal excitability by rut adenylyl cyclase (AC) that is responsible for
      Ca2+/calmodulin-dependent cAMP synthesis. Focal excitatory junctional currents
      (ejcs) demonstrated that disrupted cAMP metabolism in rut mutant boutons leads to
      decreased transmitter release, coupled with temporal dispersion and amplitude
      fluctuation of ejcs during repetitive activity. Strikingly, rut motor terminals
      displayed greatly increased variability among corresponding terminal branches of
      identified NMJs in different preparations. However, boutons throughout single
      terminal branches were relatively uniform in either WT or rut mutant larvae. The
      use of electrotonic depolarization to directly evoke transmitter release from
      axonal terminals revealed that variability in neurotransmission originated from
      varying degrees of weakened excitability in rut terminals. Pharmacological
      treatments and axonal action potential recordings raised the possibility that
      defective rut AC resulted in reduced Ca2+ currents in the nerve terminal. Thus,
      our data indicate that rut AC not only affects transmitter release machinery, but
      also plays a previously unsuspected role in local excitability control, both
      contributing to transmission level and precision along the entire axonal
      terminal.

PMID- 19101838
TI  - Exophiala spinifera as a cause of cutaneous phaeohyphomycosis: case study and
      review of the literature.
AB  - Exophiala spinifera has been reported as an agent of cutaneous disease 18 times
      in the literature. Clinical presentations of cutaneous lesions vary widely,
      including erythematous papules, verrucous plaques, and deep subcutaneous
      abscesses. The clinical distribution and course of disease are also variable,
      depending on the age and immune competency of the patient. Histologic appearance
      occurs in one of two patterns--phaeohyphomycosis or chromoblastomycosis. While E.
      spinifera appears to be susceptible to multiple antimicrobial agents in vitro,
      clinical experience with treatment modalities has been variable. Prior to the
      availability of sequencing methods, species identification was based on the
      histopathologic presentation in tissue and morphologic features of the fungus in
      culture. It is likely that E. spinifera cutaneous infections have been
      underreported due to its incorrect identification based on earlier methods. We
      report an additional case of E. spinifera phaeohyphomycosis, the first to be
      definitively identified by sequencing. In addition, we summarize the variable
      clinical, histopathologic, and morphologic features, as well as treatment
      responses described in previously reported cutaneous infections caused by E.
      spinifera.

PMID- 19101839
TI  - Lipolytic activity of chromoblastomycosis agents measured by infrared
      spectroscopy and chemometric methods.
AB  - The lipase activity of nine strains of six chromoblastomycosis agents (Fonsecaea
      pedrosoi, Phialophora verrucosa, Cladophialophora bantianum, Cladophialophora
      carrionii, Rhinocladiela aquaspersa and Exophiala jeanselmei) grown on solid
      medium was investigated using Fourier transform infrared spectroscopy and
      hierarchical clustering analysis. The data was quantified by p-nitrophenyl
      palmitate assay using partial least squares (PLS) regression. These methods
      allowed the correlation of six genera and species within the 1230-1650 and
      2800+3000 cm(-1) spectral ranges among strains grown for 14 days from their
      respective lipolytic activity with RMSEV=0.048 and R2val=0.95 and ten latent
      variables. The lipolytic activity also was predicted using PLS models with 1230
      1650 and 2800-3000 cm(-1) and 900-1450 cm(-1) spectral ranges for strains grown
      for 21 days. The separate analysis of F. pedrosoi strains yielded a prediction
      model for biomass at 21 days with RMSEV=0.065 and R2val=0.95 with eight latent
      variables using (1100-1300)+(1330-1460)+(1550-1650) cm(-1) spectral regions The
      best model obtained with the clustering of P. verrucosa, C. bantianum, C.
      carrionii, R. aquaspersa and E. jeanselmei strains was constructed with the same
      spectral ranges, but with RMSEV=0.074 and R2val=0.94 and ten latent variables.
      Infrared spectroscopy is suitable for the quantitation of extracellular lipase
      activity linked to the biomass of chromoblastomycosis agents.

PMID- 19101840
TI  - Multiple-azole-resistant Aspergillus fumigatus osteomyelitis in a patient with
      chronic granulomatous disease successfully treated with long-term oral
      posaconazole and surgery.
AB  - We describe a patient with chronic granulomatous disease and proven Aspergillus
      fumigatus osteomyelitis of the midfoot, while receiving itraconazole-prophylaxis.
      The isolate proved resistant to itraconazole as well as voriconazole, and showed
      reduced susceptibility to posaconazole. Although molecular analysis demonstrated
      the presence of a 53 base pair tandem repeat in the promoter region for cyp51A,
      i.e., the gene coding for the target enzyme of the azole antifungals, there were
      no mutations in the cyp51A gene. Since transformation of the promoter region into
      wild-type strains did not result in an azole resistant phenotype, a yet unknown
      mutation was suspected. The patient was treated with extensive surgery and two
      weeks of caspofungin therapy, followed by one year of posaconazole therapy. He
      made a complete recovery and did not experience any side effects. Long-term
      posaconazole proved to be a safe and effective treatment for multi-azole
      resistant A. fumigatus osteomyelitis in this immunocompromised patient.

PMID- 19101841
TI  - Non-aversive treatment of repetitive absconding behaviour in clients with severe
      neuropsychiatric disorders.
AB  - Research relating to the causes and treatment of absconding behaviour among
      individuals with severe neuropsychiatric disability is reviewed and a non
      aversive intervention is reported. Interventions with two clients with severe
      neuropsychiatric disability and repetitive absconding behaviour are presented in
      a multiple-baseline within-client single-case format. Multiple empirical
      treatment approaches were applied to culminate in a successful non-aversive
      intervention. The effective intervention used reinforcement approaches that were
      congruent with the client's goals rather than increased restriction. The design
      of one case included reversal, indicating that it was the intervention, not other
      factors, that reduced the absconding behaviour. Absconding attempts and
      absconding incidents were reduced to zero using non-aversive interventions where
      more restrictive interventions had failed to have a lasting impact. A counter
      intuitive non-aversive intervention was effective in eliminating dangerous
      absconding behaviour in two clients with severe neuropsychiatric disorders.

PMID- 19101842
TI  - Neural activation to babyfaced men matches activation to babies.
AB  - Behavioral data supports the commonsense view that babies elicit different
      responses than adults do. Behavioral research also has supported the babyface
      overgeneralization hypothesis that the adaptive value of responding appropriately
      to babies produces a tendency for these responses to be overgeneralized to adults
      whose facial structure resembles babies. Here we show a neural substrate for
      responses to babies and babyface overgeneralization in the amygdala and the
      fusiform face area (FFA). Both regions showed greater percentage BOLD signal
      change compared with fixation when viewing faces of babies or babyfaced men than
      maturefaced men. Viewing the first two categories also yielded greater effective
      connectivity between the two regions. Facial qualities previously shown to elicit
      strong neural activation could not account for the effects. Babyfaced men were
      distinguished only by their resemblance to babies. The preparedness to respond to
      infantile facial qualities generalizes to babyfaced men in perceivers' neural
      responses just as it does in their behavioral reactions.

PMID- 19101843
TI  - Does salience facilitate longer-term retention?
AB  - The isolation paradigm is a staple in the study of distinctiveness and memory.
      Isolated items are better remembered than non-isolated controls, and the standard
      interpretation of this effect is that subjective experience of salience recruits
      extraordinary processing to the isolated item. This interpretation is at odds
      with data showing an isolation effect when the isolate is not perceived as
      salient (e.g., von Restorff, 1933). All available research on the early isolation
      effect has tested memory after a relatively short retention interval. Perhaps the
      effect of salience on memory in the isolation paradigm would be revealed
      following longer retention intervals. The experiment reported here examines the
      effect of isolation following a 48-hour retention interval when the isolate
      evokes an experience of salience compared to when the isolate does not evoke that
      reaction. The isolation effect was substantial after the 48-hour delay but
      equally so for early and late isolation. Salience appears to have nothing to do
      with the memory processes even at the longer retention intervals.

PMID- 19101844
TI  - Clinical course during the first 10 years of ulcerative colitis: results from a
      population-based inception cohort (IBSEN Study).
AB  - OBJECTIVE: Cohort studies of unselected and newly diagnosed patients are
      essential for a better understanding of the prognosis in ulcerative colitis (UC).
      The aim of this study was to evaluate the course of UC in a population-based
      inception cohort during the first 10 years, and to identify prognostic risk
      factors based on information gathered at diagnosis. MATERIAL AND METHODS: From
      1990 to 1994, a population-based cohort of 843 patients with inflammatory bowel
      disease was enrolled in South-Eastern Norway. The cohort was systematically
      followed-up at 1, 5 and 10 years after diagnosis. RESULTS: Of 519 patients with
      UC, 423 completed the 10-year follow-up, 53 died and 43 were lost to follow-up.
      The mortality risk was not increased compared with that in the general
      population. The cumulative colectomy rate after 10 years was 9.8% (95% CI: 7.4
      12.4%). Initial presentation with extensive colitis and erythrocyte sedimentation
      rate (ESR) > or =30 mm/h was associated with an increased hazard ratio (HR)
      (3.57, 95% CI: 1.60-7.96) and age > or =50 years at diagnosis, with reduced HR
      (0.28, 95% CI: 0.12-0.65) for subsequent colectomy. Relapsing disease was noted
      in 83%, but half (48%) of the patients were relapse free during the last 5 years.
      One-fifth (69/288) of patients with proctitis or left-sided colitis had
      progressed to extensive colitis. CONCLUSIONS: The prognosis for UC during the
      first 10 years was generally good. The colectomy rate was low, and a large
      proportion of patients were in remission as time progressed. Patients with
      initially extensive colitis and elevated ESR could benefit from an early potent
      medical treatment strategy.

PMID- 19101845
TI  - ERP time course and brain areas of spontaneous and intentional goal inferences.
AB  - This study measured event-related potentials during spontaneous and intentional
      goal inferences. Participants read sentences describing the behavior of a target
      person from which a strong goal or intention could be inferred. The last word of
      each sentence determined the consistency with the goal induced during preceding
      sentences. In comparison with behaviors that were consistent with the implied
      goal, a stronger P200 waveform was obtained when the behaviors were irrelevant
      with that goal or did not contain goal-directed behavior at all, and this P200
      showed considerable parallels between spontaneous and intentional inferences.
      This indicates that goals were inferred rapidly and automatically while reading
      the behaviors, irrespective of the participants' spontaneous or intentional
      instructions. In line with this, source localization (LORETA) of the event
      related potentials shows predominantly activation in the temporoparietal junction
      (TPJ) during and immediately after goal detection (225-300 ms). Before and after
      this time interval, however, activation is stronger at the TPJ during spontaneous
      processing, and stronger at the medial prefrontal cortex (mPFC) during
      intentional processing. Memory measures taken after the presentation of the
      stimulus materials support the occurrence of goal inferences and show significant
      correlations with the neural components, indicating that these components are
      valid neural indices of spontaneous and intentional goal inferences. The results
      are highly similar to previous ERP research on trait inferences that revealed a
      similar division of brain activation for spontaneous (TPJ) and intentional (mPFC)
      processes, but appearing later at about 600 ms, pointing to similar brain areas
      recruited for social inferences, but at different timings for different inference
      types.

PMID- 19101848
TI  - Diabetes mellitus and outcomes of colorectal cancer.
AB  - BACKGROUND: Patients with diabetes mellitus have an increased risk of colorectal
      cancer. However, there is limited information on the outcome for diabetic
      patients diagnosed with this type of cancer. METHODS: The health records of all 1
      194 patients treated for colorectal adenocarcinoma at Levanger Hospital from 1980
      2004 were reviewed. Diabetes status and prognostic factors were registered.
      Primary endpoints were cancer specific survival and overall survival. RESULTS:
      There were no significant differences between diabetic patients and non-diabetic
      patients concerning stage, grade, treatment, infective or non-infective
      postoperative complications, hospital stay, or 30 days mortality after
      laparotomy. After a curative resection, the estimated 5-year cancer specific
      survival in 97 diabetic patients was 73% (95% CI 60-87) and 79% (95% CI 75-82) in
      1097 non-diabetic patients (not significant). The estimated overall 5-year
      survival in patients treated with curative intent was 46% (95% CI 33-59) in
      diabetic patients and 65% (95% CI 62-69) in non-diabetic patients (p<0.001). The
      diabetic patients were significantly older and more frequently had cardiac
      diseases. CONCLUSION: Diabetes mellitus did not affect the short-term survival or
      the cancer specific survival. A shorter overall survival was associated with
      cardiac diseases and higher age.

PMID- 19101849
TI  - Sulcus configurations of vocal folds during phonation.
AB  - CONCLUSION: A detailed understanding of clinical and voice characteristics will
      help to differentiate sulcus configuration and plan rational management
      strategies for each type. OBJECTIVES: To investigate the clinical and voice
      characteristics of patients with sulcus configuration of vocal folds during
      phonation. PATIENTS AND METHODS: A total of 146 patients with bilateral sulcus
      configuration of vocal folds were enrolled in this study. Based on
      videostroboscopic findings, patients were classified into three groups:
      physiologic sulcus configuration group (type I), pathologic sulcus configuration
      group, including sulcus vergeture (type II), and sulcus vocalis (type III). Voice
      analyses were obtained from a recorded speech sample. RESULTS: Thirty-two
      patients (21.9%) were type I, 61 (41.8%) were type II, and 53 (36.3%) were type
      III. Different sulcus configuration groups had significantly different roughness
      and mean fundamental frequency. Type III was significantly different from type I
      and type II in grade, breathiness, mean flow rate, subglottic pressure, maximum
      phonation time, Jitter%, and harmonics to noise ratio. The pathologic sulcus
      showed distinctive features in electroglottograph waveform.

PMID- 19101850
TI  - Correction of displaced peritoneal dialysis catheters with an angular stiff rod.
AB  - BACKGROUND: Fluoroscopically guided guidewire manipulations are readily available
      and inexpensive methods of correcting malfunctioning peritoneal dialysis
      catheters, with reported success rates ranging from 25% to 67%. PURPOSE: To
      improve the success rates of guidewire manipulations with a modified technique.
      MATERIAL AND METHODS: Using a stiff rod and a stiff wire under fluoroscopy
      guidance, catheters that had migrated were drawn back into the rectovesical
      pouch. An angular rod was used to lever the catheter downward, and the guidewire
      was used to push the catheter down. RESULTS: No complications developed, and
      immediate success was achieved in 13 of 14 interventions. With this technique,
      catheter patency in chronic ambulatory peritoneal dialysis (CAPD) patients
      (11/12) was higher than that of previously reported methods. Durable success was
      maintained in nine of 12 patients after a single intervention. All re
      manipulations (2/2) were successful. CONCLUSION: Although used in only 14
      interventions in 12 patients, the outcome was promising. This method is a safe
      and favorable alternative to other guidewire manipulations, based on absence of
      complications and high success.

PMID- 19101851
TI  - Magnetic resonance imaging-guided renal artery stent placement in a Swine model:
      comparison of two tracking techniques.
AB  - BACKGROUND: Magnetic resonance (MR)-guided interventions have evolved from a pure
      research application to a preclinical method over the last decade. Among the
      device-tracking techniques, susceptibility artifact-based tracking relies on the
      contrast between the surrounding blood and the device, and radiofrequency coil
      based tracking relies on the local gradient field amplification in a resonating
      circuit attached to the interventional device. PURPOSE: To evaluate the
      feasibility and precision of susceptibility artifact-based and microcoil-based MR
      guidance methods for renal artery stent placement in a swine model. MATERIAL AND
      METHODS: MR imaging-guided renal artery stent placements were performed in six
      fully anesthetized pigs using a 1.5T short-bore MR scanner. Susceptibility
      artifact-based tracking with manual scan-plane adjustments and microcoil tracking
      with automatic scan-plane adjustments were used for renal artery stent placements
      in three pigs in each group. With both methods, near real-time steady-state free
      precession (SSFP) imaging was used. Differences between the two tracking
      approaches on stenting time, total procedure time, and stent position were
      measured. RESULTS: The microcoil-based approach yielded a shorter mean procedure
      time (17 vs. 23 min). There was no relevant difference for the mean stenting time
      (12 vs. 13 min). The mean stent deviation from the aortic wall with the
      susceptibility approach was larger than with the microcoil approach (10 vs. 4.0
      mm). CONCLUSION: For MRI-guided renal artery stent placement, the microcoil-based
      technique had a shorter procedure time and a higher stent placement precision
      than the susceptibility artifact-based approach.

PMID- 19101852
TI  - Complete ablation of a renal tumor abutting the inferior vena cava using a
      radiofrequency electrode as a lever: a case report.
AB  - Radiofrequency ablation is accepted as a minimally invasive treatment for renal
      tumors in patients who are poor candidates for surgery. However, ablation of
      tumors that abut large vessels is likely to be incomplete due to the heat-sink
      effect or may result in vascular injury. We report a case of a renal tumor
      abutting the inferior vena cava, which was successfully treated with
      radiofrequency ablation, with an emphasis on the technical aspects required to
      avoid both incomplete ablation and vascular injury by using a radiofrequency
      electrode as a lever.

PMID- 19101853
TI  - Cardiovascular disease risk factor (CVDRF) associated waist circumference
      patterns in obese-prone children.
AB  - OBJECTIVES: The present study tested whether children born at high risk (HR)
      compared with low risk (LR) for obesity are more likely to have a waist
      circumference (WC) associated with cardiovascular disease risk factors (CVDRF-WC)
      and tested whether CVDRF-WC status tracks over time. METHODS: This prospective
      cohort study involved 71 children, three to eight years, who were divided into
      two groups, LR (n = 37) and HR (n = 34), based upon maternal prepregnancy body
      mass index (BMI). HR subjects were subdivided into HR normal-weight (HRNW) and HR
      overweight (HROW) groups, based on BMI > or = 85%. Children were classified as
      having or not having a CVDRF-WC at each year, using age- and gender-specific WC
      cut-offs. Anthropometry was assessed annually. RESULTS: Although HR children had
      a significantly greater mean WC than LR children at years 5-8 (p < 0.03), these
      differences became non-significant after adjusting for BMI. HROW were more likely
      to have a CVDRF-WC status (p < or = 0.0001) at age 4 years (10%, 5%, vs. 58%), 5
      years (3%, 10%, vs. 60%), 6 years (0%, 0%, vs. 70%), 7 years (0%, 0%, vs. 50%) to
      8 years (0%, 0%, vs. 55%) than LR and HRNW. Although 60-100% of the children
      tracked CVDRF-WC status, higher proportions of HROW children (0-40%) transitioned
      into having a CVDRF-WC, compared with LR (0-6%) and HRNW (0-9%). CONCLUSIONS:
      HROW were more likely to have or develop a CVDRF-WC. Although the effects of
      obesity risk on WC may be secondary to BMI, clinically assessing WC in obese
      prone children may help identify youth at risk for obesity-related complications.

PMID- 19101855
TI  - Exercise training in older patients with systolic heart failure: adherence,
      exercise capacity, inflammation and glycemic control.
AB  - OBJECTIVES: Training improves exercise capacity in patients with heart failure
      (CHF) but most evidence is on selected younger patients with systolic CHF.
      DESIGN: All patients diagnosed with CHF over 3 years were screened for inclusion
      and exclusion criteria. Fifty two patients with systolic CHF (LVEF<45, NYHA II
      III) received supervised exercise training twice weekly for 8 weeks. RESULTS:
      Mean age was 68.2 (+/-SD 11.3) years. Despite marked improvements in physical
      fitness (workload, 6 minute walk test, incremental shuttle walk test and sit to
      stand test), there were no changes in serological markers of glycemic control
      (glucose, insulin, glycerol, free fatty acids, HbA1c), inflammation and
      endothelial function (hsCRP, orosomucoid, interleukin 6, TNF-alpha, urine
      orosomucoid and -albumin/creatinin), lipid metabolism, NT-proBNP or other
      regulatory hormones (cortisol, epinephrine and IGF-1). There were no changes in
      quality of life. CONCLUSIONS: The effect of exercise training in these older CHF
      patients was not as impressive as reported in younger and more selected patients.
      More studies on the efficiency of exercise training that reflect the age- and co
      morbidity of the majority of CHF-patients are needed.

PMID- 19101857
TI  - Rectal NO and fecal calprotectin in IBD.

PMID- 19101858
TI  - Nocardial infection in Crete, Greece: review of fifteen cases from 2003 to 2007.
AB  - During a 5-y period (2003 - 2007), nocardial infections were diagnosed in 15
      patients admitted to the University Hospital of Heraklion, Crete, Greece. Nine
      patients (60%) had 1 or more underlying conditions predisposing to nocardiosis.
      The skin was involved in 10 cases, followed by the lung in 4. One patient had
      disseminated disease. Five different species were identified: N. brasiliensis (n
      =7), N. otitidiscaviarum (n=4), N. abscessus (n=2), N. transvalensis (n=1), and
      N. farcinica (n=1). The most common species was N. brasiliensis. All isolates
      were sensitive to linezolid, moxifloxacin, and tigecycline, and 80% of them to
      trimethoprim-sulfamethoxazole. Antibiotics were given to all 15 patients. A
      clinical response was observed in 14 of them, while 1 died of nocardiosis.
      Nocardiosis is a rare but sometimes life-threatening infection, complicating
      immunosuppression. Early diagnosis and timely administration of appropriate
      treatment result in a favourable outcome.

PMID- 19101859
TI  - Zoledronic acid induces caspase-dependent apoptosis in renal cancer cell lines.
AB  - OBJECTIVE: To study and characterize the potential antitumoral effects of
      zoledronic acid (ZA) on renal cancer cell lines in vitro. MATERIAL AND METHODS:
      Three different and well-characterized renal cancer cell lines were studied,
      namely ACHN, A-498 and CAKI-2. The cytotoxic potential of ZA was evaluated using
      a fluorometric microculture cytotoxic assay. The degree of M30 induction
      following ZA treatment was measured using an M30 enzyme-linked immunosorbent
      assay (ELISA), and the blockage of this effect was studied using a pan-caspase
      inhibitor. Immunofluorescence of the M30 neoepitope was performed to visualize
      the M30-inducing properties of ZA. RESULTS: A significant reduction in viable
      cells was seen for all three cell lines following treatment with ZA, compared
      with untreated controls. This effect was most pronounced for the ACHN cells, as
      only 4% were viable following incubation with ZA for 72 h. A concomitant increase
      in the apoptosis significant caspase-dependent M30 antigen was demonstrated. This
      effect could be blocked by the pan-caspase inhibitor Z-VAD. CONCLUSIONS: ZA
      exerts cytotoxic effects on renal cancer cell lines in vitro. These include
      caspase-dependent induction of apoptosis, which can be quantified and visualized
      using M30 ELISA and immunofluorescence, respectively. The clinical relevance of
      this finding needs to be further investigated, but these results indicate that ZA
      may be a treatment alternative for selected patients with skeletal metastasized
      renal cell cancer, particularly for those with impaired performance status
      without other treatment options.

PMID- 19101860
TI  - President's Annual State of the Academy Report.

PMID- 19101874
TI  - [Treatment of benzodiazepine dependence: new insights into an old problem].

PMID- 19101875
TI  - [Benzodiazepine dependence: causalities and treatment options].
AB  - Benzodiazepines are very often prescribed because of their anxiolytic, sedative
      and hypnotic properties. However, long term treatment is associated with
      development of benzodiazepine dependence. Besides development of physical
      dependence, which is linked to a typical benzodiazepine withdrawal syndrome when
      drug intake is discontinued, also behavioural addiction to benzodiazepines has
      been described. Benzodiazepines are known to enhance GABAergic neurotransmission.
      Counter regulation of enhanced GABAergic neurotransmission by enhancement of
      glutamatergic neurotransmission is thought to be one reason underlying the
      typical symptoms of benzodiazepine withdrawal. Also alterations in the expression
      of neuropeptides like Corticotropin Releasing Hormone and Neuropeptide Y are
      thought to be involved in the development of benzodiazepine dependence. However,
      until today the knowledge of neural mechanisms underlying the development of
      benzodiazepine dependence remains incomplete. Because even long term treatment
      with small doses of benzodiazepines is associated with adverse reactions like
      cognitive dysfunctions withdrawal from benzodiazepines should be aimed.
      Anticonvulsants and antidepressants seem to reduce the intensity of
      benzodiazepine withdrawal and to enhance long term prognosis of dependence.

PMID- 19101876
TI  - [Body Integrity Identity Disorder (BIID): interrogation of patients and theories
      for explanation].
AB  - Apotemnophilia, Amputee Identity Disorder or Body Integrity Identity Disorder
      (BIID) is the intensive feeling that the body will be "more complete" after
      amputation of a limb. The article disputes the question of matching personality
      characteristics of these subjects and asks for motives. Based on reports of nine
      individuals, triggering experiences are referred. In contrast to other children,
      often these subjects were fascinated by the sight of a handicapped person. In the
      article is investigated, whether the concerned limb showed more affections.
      Described is typical pretending behavior. Parallels to body dysmorphic disorder
      (BDD), fetishism, or delusions are investigated. These were minor, in most cases
      the wish was fixated on a specific limb, the subjects were aware of the abnormity
      of their desire and quarreled with the pros and cons. Sexual motives were found
      in one third. Some of the interviewed persons were in medical or psychological
      therapy; this did not let the desire disappear. In several BIID sufferers the
      wish for amputation changed, e. g. from the left to the right leg. This finding
      is not in accordance with the brain-dysfunction-theory. These people rather have
      an ideal of a "perfect" body minus one arm or leg. Most admire the beauty of a
      stump, and see amputees as "heroes" who still master their life in spite of their
      handicap. BIID is not a homogenous disturbance, one should separate three axes:
      1. Strength of neuronal dysfunction, 2. Psychic components (e. g. secondary
      morbid gain) and 3. Intensity of sexual interests.

PMID- 19101877
TI  - [OSCE in the neurology clerkship. Experiences at the neurological department of
      the university hospital Erlangen].
AB  - BACKGROUND: In the German medical education program practical examinations at the
      end of the neurology clerkship are sparsely performed. By this way, motivation
      for practical learning and a method to assure quality of learning are not used.
      METHOD: The Anglo-Saxon concept of "objective structured clinical examination"
      (OSCE) is picked up and implemented as a practical examination at the end of the
      neurology clerkship of medical students in their 4th and 5th year. A catalogue of
      learning goals was defined and an OSCE of 5 stations was developed. A standard of
      a successful examination was defined. In two OSCE stations the competence in
      clinical decision making and reasoning were tested, in two stations the
      competence in practical examination skills and in one station the practical skill
      to perform a lumbar puncture at the phantom. The results of the OSCE stations
      were analysed for task difficulty, discriminatory power, normalized
      discrimination index and reliability. Using a questionnaire, the students
      evaluated the OSCE. RESULTS: N = 123 students (73 female, 50 male) with a mean
      age of 26.1 years (22 - 46 years) participated. The mean score was 40 +/- 3.6 of
      a total of 50 points (range 29 - 46). Female students (40.8 +/- 3.1) scored
      significantly higher than male ones (38.8 +/- 4; p = .002). One student (0.8 %)
      failed the examination. The difficulty of the stations ranged between 0.63 and
      0.91, normalized discrimination index between 0.1 and 0.18 and the discriminatory
      power from r = 0.25 to r = 0.53. The reliability of the 5 stations was 0.65
      (Cronbach's alpha). In the evaluation, the rating for innovation, organisation,
      length, clarity of the tasks, clinical reality and compatibility with general
      physician's competence, atmosphere during the examination and fairness was
      extremely positive. Most students would prefer an OSCE compared with a multiple
      choice test. CONCLUSION: An OSCE at the end of the neurology clerkship is
      feasible. The quantitative analyses of the results are concordant with
      requirements of medical examinations. The OSCE is positively evaluated by the
      students.

PMID- 19101878
TI  - [Cognitive dysfunction as a hidden multiple sclerosis related symptom relevant
      for an expert appraisal].
AB  - We report on a patient with multiple sclerosis (MS), who had severe cognitive
      dysfunction despite only mild changes in cerebral magnetic resonance imaging
      (cMRI). The severe MS-related cognitive deficits were disclosed only in a
      comprehensive neuropsychological evaluation. A previous appraiser was not able to
      detect these neuropsychological deficits as he did not conduct an appropriate
      neuropsychological assessment. The expert appraisal had been performed to decide
      whether the MS-related deficits would make the patient eligible to receive
      pension payments from a private pension insurance. Only after a subsequent
      neuropsychological expert appraisal the insurance company had to pay several ten
      thousands of Euro as decided by judicial decree. The presented case impressingly
      demonstrates that the so called hidden symptoms of MS such as fatigue or
      cognitive dysfunction are often not identified by treating physicians and in
      medico-legal evaluations. We therefore postulate that comprehensive
      neuropsychological evaluation is mandatory to perform expert appraisals to assess
      occupational disability in MS patients.

PMID- 19101879
TI  - [Central pontine myelinolysis].

PMID- 19101880
TI  - Onyx embolization as a first line treatment for intracranial dural arteriovenous
      fistulas with cortical venous reflux.
AB  - PURPOSE: Our purpose was to present our experience regarding embolization of
      intracranial dural arteriovenous fistulas (DAVFs) with cortical venous reflux
      using Onyx, a non-adhesive liquid embolic agent. MATERIALS AND METHODS: From
      January 2006 to December 2007, 16 patients (12 men and 4 women) with a mean age
      of 61 years (range 42 - 78) with an intracranial DAVF with cortical venous reflux
      underwent at least one transarterial embolization using Onyx. According to the
      Cognard classification, 2 lesions were grade V, 5 were grade IV, 6 were grade
      III, 2 were grade IIa+b, and 1 was grade IIb. The clinical presentation included
      5 hemorrhagic deficits, 10 non-hemorrhagic manifestations, and 1 patient was
      asymptomatic. RESULTS: Twenty-four embolization sessions were performed in 16
      patients with an average of 3 arterial feeders (range 1 - 9) embolized per DAVF.
      Immediately after embolization, complete occlusion was achieved in 9/16 (56%)
      patients after the first session. Further postembolization surgical treatment was
      performed in 3 patients. Partial reperfusion occurred in 1 patient at the time of
      mean follow-up of 3.7 months (range 0 - 12). Treatment has been completed for
      11/16 patients with angiographic cure in 10/11 (91%). An infratentorial bleeding
      complication related to embolization occurred in one patient with temporary
      worsening of the patient's gait disturbance. At the time of mean clinical follow
      up of 4.5 months (range 0 - 12), no procedure-related permanent morbidity was
      added to our cohort. CONCLUSION: According to our experience, embolization of
      intracranial DAVFs with cortical venous drainage using Onyx is feasible with
      promising results, indicating stability at the time of mid-term follow-up. In
      very complex DAVFs additional embolization material might be necessary, and in
      some cases surgery is warranted.

PMID- 19101881
TI  - [MRI-based flow measurements in the main pulmonary artery to detect pulmonary
      arterial hypertension in patients with cystic fibrosis].
AB  - PURPOSE: Development of pulmonary arterial hypertension (PH) is a common problem
      in the course of patients suffering from cystic fibrosis (CF). This study was
      performed to evaluate MRI based flow measurements (MR(venc); Velocity ENCoding)
      to detect signs of an evolving PH in patients suffering from CF. MATERIALS AND
      METHODS: 48 patients (median age: 16 years, range: 10 - 40 years, 25 female)
      suffering from CF of different severity (mean FEV (1): 74% +/- 23, mean Shwachman
      score: 63 +/- 10) were examined using MRI based flow measurements of the main
      pulmonary artery (MPA). Phase-contrast flash sequences (TR: 9.6 ms, TE: 2.5 ms,
      bandwidth: 1395 Hertz/Pixel) were utilized. Results were compared to an age- and
      sex-matched group of 48 healthy subjects. Analyzed flow data where: heart
      frequency (HF), cardiac output (HZV), acceleration time (AT), proportional
      acceleration time related to heart rate (ATr), mean systolic blood velocity
      (MFG), peak velocity (Peak), maximum fow (Fluss(max)), mean flow (Fluss(mitt))
      and distensibility (Dist). RESULTS: The comparison of means revealed significant
      differences only for MFG, Fluss(max) and Dist, but overlap was marked. However,
      using a scatter-plot of AT versus MFG, it was possible to identify five CF
      patients demonstrating definite signs of PH: AT = 81 ms +/- 14, MFG = 46 +/- 11
      cm/s, Dist = 41% +/- 7. These CF-patients where the most severely affected in the
      investigated group, two of them were listed for complete heart and lung
      transplantation. The comparison of this subgroup and the remaining CF-patients
      revealed a highly significant difference for the AT (p = 0.000001) without
      overlap. CONCLUSION: Screening of CF-patients for the development of PH using
      MRvenc of the MPA is not possible. In later stages of disease, the quantification
      of AT, MFG and Dist in the MPA may be useful for the detection, follow-up and
      control of therapy of PH. MR(venc) of the MPA completes the MRI-based follow-up
      of lung parenchyma damage in patients suffering from CF.

PMID- 19101882
TI  - Prevalence for the cluster of risk factors of the Metabolic Vascular Syndrome in
      a working population in Germany.

PMID- 19101883
TI  - Assessment of pituitary and steroid hormones and members of the TGF-beta
      superfamily for ovarian function in patients with congenital uterus and vaginal
      aplasia (MRKH syndrome).
AB  - Patients with Mayer-Rokitanski-Kuster-Hauser (MRKH) syndrome have congenital
      uterine and vaginal aplasia. The main question of this study was, if the absence
      of a uterus along with other genital and organ malformations could contribute to
      hormone or other growth factor protein fluctuations involved in communication
      between the hypothalamus-pituitary axis, ovaries and uterus. Serum from 56 MRKH
      patients (mean 27.6 years) and 22 female controls (mean 30.7 years) were analyzed
      using ELISA to determine levels of pituitary and steroid hormones (LH, FSH,
      estradiol, progesterone), growth factors of the TGF-beta superfamily like activin
      A, inhibin B, and anti-Mullerian hormone (AMH). All serum levels were analyzed in
      relation to other organ malformations. Compared to controls, all 56 patients,
      including 5% with streak ovaries or unilateral ovarian aplasia, were generally
      similar in hormone and growth factor levels and could be grouped into hormonal
      phases. However, compared to controls LH/FSH and FSH/LH ratios of patients had
      significantly higher and lower mean values, of 2.75-fold (p=0.015) and 1.9-fold
      (p=0.002), respectively. Undetectable inhibin B levels of<10 pg/ml (p=0.05) were
      noted in 41.1% of MRKH patients, resulting in significantly higher activin
      A/inhibin B ratios (p<0.001). MRKH patients have hormonal phases supporting
      ovarian function, but patients with low FSH/LH ratios and undetectable inhibin B
      levels (<10 pg/ml) could represent cycle phasing irregularities. A model is
      discussed regarding our findings and the loss of ovarian-uterine communication.

PMID- 19101884
TI  - Metabolic profiling of echinacea genotypes and a test of alternative taxonomic
      treatments.
AB  - The genus Echinacea is used as an herbal medicine to treat a variety of ailments.
      To better understand its potential chemical variation, 40 Echinacea accessions
      encompassing broad geographical and morphological diversity were evaluated under
      controlled conditions. Metabolites of roots from these accessions were analyzed
      by HPLC-photo diode array (HPLC-PDA), GC-MS, and multivariate statistical
      methods. In total, 43 lipophilic metabolites, including 24 unknown compounds,
      were detected. Weighted principal component analysis (WPCA) and clustering
      analysis of the levels of these metabolites across Echinacea accessions, based on
      Canberra distances, allowed us to test two alternative taxonomic treatments of
      the genus, with the further goal of facilitating accession identification. A
      widely used system developed by McGregor based primarily on morphological
      features was more congruent with the dendrogram generated from the lipophilic
      metabolite data than the system more recently developed by Binns et al. Our data
      support the hypothesis that Echinacea pallida is a diverse allopolyploid,
      incorporating the genomes of Echinacea simulata and another taxon, possibly
      Echinacea sanguinea. Finally, most recognized taxa of Echinacea can be identified
      by their distinct lipophilic metabolite fingerprints.

PMID- 19101885
TI  - Isolation and biological activities of neomyrrhaol and other terpenes from the
      resin of Commiphora myrrha.
AB  - A new cycloartane-type triterpene named cycloartane-1alpha,2alpha,3beta,25
      tetraol (neomyrrhaol) (1), along with four known terpenes, sandaracopimaric acid
      (2), abietic acid (3), 2-methoxy-5-acetoxyfruranogermacr-1(10)-en-6-one (4), and
      dehydroabietic acid (5) have been isolated from the resin of COMMIPHORA MYRRHA.
      Their structures were elucidated by means of 1D, 2 D NMR and HR-mass
      spectroscopy. Compounds 2-5 are known compounds but not previously isolated from
      the resin of C. MYRRHA. Compounds 4 and 5 exhibited significant aromatase
      inhibiting activity with IC50 values at 0.2 microM and 0.3 microM, respectively.
      As shown in the MTT assay, 2, 3, 4, and 5 had inhibitory effects on HUVEC growth
      with IC50 values of 0.122 microM (2), 0.125 microM (3), 0.069 microM (5).
      Compounds 1-5 did not inhibit contraction of the isolated uterine and did not
      protect HUVEC from damage induced by H2O2 at the tested concentration.

PMID- 19101887
TI  - Plant analysis 2008--planar chromatography.
AB  - For 70 years, planar chromatography has been closely connected with the analysis
      of plants. Also today in its most advanced form "high performance thin-layer
      chromatography" (HPTLC), the technique plays an important role in identification
      of medicinal plants and dietary supplements. Detection of adulteration and
      quantitative determination of marker substances are other widely used
      applications. The advancement of instrumentation and methodological concepts has
      created a basis for reliable qualitative and quantitative results in HPTLC.
      Remarkable progress has been made in the manageability of the entire planar
      chromatographic process, particularly in the control of chromatogram development
      and the utilization of images to obtain and compare information about separated
      samples. Integration of biological detection systems as well as hyphenation to
      mass spectrometry has widened the applicability of planar chromatography as an
      analytical technique that is both orthogonal and complementary to HPLC.

PMID- 19101886
TI  - Acasiane A and B and farnesirane A and B, diterpene derivatives from the roots of
      Acacia farnesiana.
AB  - Four new diterpenes, acasiane A ( 1), acasiane B ( 2), farnesirane A ( 3), and
      farnesirane B ( 4), along with three known diterpenes ( 5 - 7), two triterpenes (
      8 and 9), and eight flavonoids ( 10 - 17) were isolated from the roots of Acacia
      farnesiana. The structures and relative configurations of these compounds were
      determined by various spectroscopic and x-ray analyses. All isolated compounds
      were evaluated for their in vitro cytotoxic activities against six human cancer
      cell lines (Hep G2, Hep 3B, MDA-MB-231, MCF-7, A549, and Ca9 - 22) with the MTT
      method. Betulinic acid ( 8) displayed moderate cytotoxicity (1.70 - 5.74
      microg/mL) towards five human cancer cell lines and the flavonoids had slight
      effects. In addition, 8, diosmetin ( 13), and 3',4',5-trihydroxy-7-methoxyflavone
      ( 15) slightly inhibited superoxide anion generation or elastase release by human
      neutrophils, indicating moderate anti-inflammatory activities.

PMID- 19101888
TI  - Acetylcholinesterase activity of alkaloids from the leaves of Waltheria
      brachypetala.
AB  - Chemical investigation of the leaves of Waltheria brachypetala Turks
      (Sterculiaceae) resulted in the isolation of quinolinone alkaloids, waltherione
      A, waltherione-B (N-methylwaltherione-A), 8-methoxyflindersine, and the cyclic
      peptide alkaloid waltherine. The inhibition of activity of acetylcholinesterase
      (AChE) by the alkaloids was evaluated. Waltherione-A, waltherione-B and
      waltherine showed significant activity.

PMID- 19101889
TI  - [Diagnostic value of unspecific requested and implemented MRI for detecting
      intracarpal lesions, compared to arthroscopic findings at 217 patients].
AB  - AIM: The purpose of this study was to evaluate the diagnostic value of MRI for
      detecting intracarpal lesions in clinical routine. PATIENTS AND MATERIALS: In a
      retrospective study, we reviewed the charts of 506 patients who had undergone
      wrist arthroscopy in our department between May 1998 and November 2002. Out of
      506 patients 217 had an MRI. The MRI was performed at 31 different radiology
      facilities using a number of techniques. The MRI results were compared with the
      arthroscopic findings, taking the arthroscopic results as a "gold standard"
      (sensitivity = SEN, specificity = SPE, positive predictive value = PPV, negative
      predictive value = NPV, accuracy = ACC). RESULTS: The following results were
      found: For tears of the scapholunate ligament the avalues are SEN 18.5 %, SPE 95
      %, PPV 71 %, NPV 66 %, ACC66 %. Not one of 16 tears of the lunotriquetral
      ligament was found by MRI. CONCLUSION: In our data we found a low sensitivity for
      unspecific requested and implemented MRI for detecting intracarpal lesions.
      Therefore the indication for MRI should only be made after experienced hand
      surgeons have examined the wrist. In our opinion, only direct MR-arthrography is
      equal to arthroscopy, so that only an experienced radiologist who is familiar
      with this technique should perform the MRI diagnostics of the hand.

PMID- 19101890
TI  - [Antibiosis instead of the scalpel: new findings for Crohn disease].

PMID- 19101891
TI  - Degradable polymeric materials for osteosynthesis: tutorial.
AB  - This report summarizes the state of the art and recent developments and advances
      in the use of degradable polymers devices for osteosynthesis. The current
      generation of biodegradable polymeric implants for bone repair utilising designs
      copied from metal implants, originates from the concept that devices should be
      supportive and as "inert" substitute to bone tissue. Today degradable polymeric
      devices for osteosynthesis are successful in low or mild load bearing
      applications. However, the lack of carefully controlled randomized prospective
      trials that document their efficacy in treating a particular fracture pattern is
      still an issue. Then, the choice between degradable and non-degradable devices
      must be carefully weighed and depends on many factors such as the patient age and
      condition, the type of fracture, the risk of infection, etc. The improvement of
      the biodegradable devices mechanical properties and their degradation behaviour
      will have to be achieved to broaden their use. The next generation of
      biodegradable implants will probably see the implementation of the recent gained
      knowledge in cell-material interactions and cells therapy, with a better control
      of the spatial and temporal interfaces between the material and the surrounding
      bone tissue.

PMID- 19101892
TI  - Cartilage tissue engineering using pre-aggregated human articular chondrocytes.
AB  - In this study, we first aimed at determining whether human articular chondrocytes
      (HAC) proliferate in aggregates in the presence of strong chondrocyte mitogens.
      We then investigated if the aggregated cells have an enhanced chondrogenic
      capacity as compared to cells cultured in monolayer. HAC from four donors were
      cultured in tissue culture dishes either untreated or coated with 1% agarose in
      the presence of TGFbeta-1, FGF-2 and PDGF-BB. Proliferation and stage of
      differentiation were assessed by measuring respectively DNA contents and type II
      collagen mRNA. Expanded cells were induced to differentiate in pellets or in
      Hyaff-11 meshes and the formed tissues were analysed biochemically for
      glycosaminoglycans (GAG) and DNA, and histologically by Safranin O staining. The
      amount of DNA in aggregate cultures increased significantly from day 2 to day 6
      (by 3.2-fold), but did not further increase with additional culture time.
      Expression of type II collagen mRNA was about two orders of magnitude higher in
      aggregated HAC as compared to monolayer expanded cells. Pellets generated by
      aggregated HAC were generally more intensely stained for GAG than those generated
      by monolayer-expanded cells. Scaffolds seeded with aggregates accumulated more
      GAG (1.3-fold) than scaffolds seeded with monolayer expanded HAC. In conclusion,
      this study showed that HAC culture in aggregates does not support a relevant
      degree of expansion. However, aggregation of expanded HAC prior to loading into a
      porous scaffold enhances the quality of the resulting tissues and could thus be
      introduced as an intermediate culture phase in the manufacture of engineered
      cartilage grafts.

PMID- 19101893
TI  - Surgical repair of posterior urethral defects: review of literature and
      presentation of experiences.
AB  - INTRODUCTION: The main objective of the present review article was to study the
      different aspects of reconstructive surgery for posterior urethral defects by
      reviewing the published articles and presentation of our experiences in the
      reconstructive urology division at Shohada-e-Tajrish hospital. MATERIALS AND
      METHODS: The Medline was searched with the keywords of posterior urethroplasty,
      end-to-end anastomosis, excisional urethroplasty, anastomotic urethroplasty,
      pelvic fracture, bulboprostatic anastomosis, and urethral repair. The search was
      limited to papers published from 1980 to September 2008. We selected the relevant
      published articles in this database and also presented our experience at our
      reconstructive urology division. RESULTS: Of over 5000 search results, we
      selected 38 relevant articles with substantial contribution to the subject.
      Pelvic fracture due to accidents was the most common etiology of pelvic fracture
      urethral distraction defect that usually involved the membranous urethra.
      Surgical treatment of this disorder with perineal anastomotic urethroplasty was
      accompanied by a success rate of 82% to 95% in different studies. The most
      important complications of this surgery include urinary incontinence and
      impotence; however, the incidence of these complications has been reduced by
      using new surgical techniques. CONCLUSION: Complete preoperative assessment, the
      use of suitable reconstructive techniques, and in particular, the use of flexible
      cystoscopy can lead to acceptable outcomes of the surgical repair of pelvic
      fracture urethral distraction defects.

PMID- 19101894
TI  - Intravesical foreign bodies: review and current management strategies.
AB  - INTRODUCTION: The aim of this study was to evaluate the cause, diagnosis, and
      management of intravesical foreign bodies in patients treated at our hospital and
      to review and update management of intravesical foreign bodies reported in the
      current literature. MATERIALS AND METHODS: Sixteen patients had been treated for
      intravesical foreign bodies at Nishtar Medical College Hospital, Multan, Pakistan
      during a 5-year period. Records of these patients were analyzed retrospectively
      for etiology, presentation, diagnosis, and management. RESULTS: The age of the
      patients ranged from 14 to 70 years and 10 of them were men. Seven patients
      (43.8%) had iatrogenic intravesical foreign bodies, 5 (31.3%) had migrated
      foreign bodies from the adjacent organs, and 4 (25.0%) had self-introduced
      foreign bodies into the bladder. The objects included copper wire, carrot, lead
      pencil, intrauterine device, surgical gauze, pieces of Foley catheter, and teflon
      beak of resectoscope sheath. The most common presenting symptoms were urinary
      frequency and dysuria. Endoscopic retrieval was possible in 8 (50.0%) patients,
      and the remaining underwent open cystostomy. CONCLUSION: Intravesical foreign
      bodies should be included in the differential diagnosis of patients with chronic
      lower urinary tract problems. Radiological evaluation is necessary to determine
      the exact size, number, and nature of them. The most suitable method for removal
      of intravesical foreign bodies depends on the nature of the foreign body, age of
      the patient, and available expertise and equipment. Most intravesical foreign
      bodies can be retrieved with minimally invasive techniques.

PMID- 19101895
TI  - Retroperitoneal ganglioneuroma.

PMID- 19101896
TI  - Lubrication of circumcision site for prevention of meatal stenosis in children
      younger than 2 years old.
AB  - INTRODUCTION: Circumcision is one of the most common surgical operations
      throughout the world, and meatal stenosis is one its late complications. We
      evaluated the topical use of a lubricant jelly after circumcision in boys in
      order to reduce the risk of meatal stenosis. MATERIALS AND METHODS: A randomized
      control trial was performed, in which 2 groups of boys younger the 2 years old
      underwent circumcision according to the sleeve method. The parents in the study
      group were instructed to use petroleum jelly on the circumcision site after each
      diaper change for 6 months. In the control group, no topical medication was used.
      The children were followed up regularly and evaluated for meatal stenosis,
      bleeding, infection, and recovery time. RESULTS: A total of 197 boys in each
      group completed the study. None of the children in the study group but 13 (6.6%)
      in the control group developed meatal stenosis (P < .001). Infection of the
      circumcision site was seen in 3 (1.5%) and 23 (11.7%) children of the lubricant
      and control groups, respectively (P < .001), and bleeding was seen in 6 (3.0%)
      and 37 (18.8%), respectively (P < .001). The mean time of recovery in the
      lubricant group was 3.8 +/- 1.2 days, while it was 6.9 +/- 4.2 days in the
      control group (P = .03). CONCLUSION: Based on the findings of this study, it
      seems logical to use a lubricant jelly for reducing postcircumcision meatal
      stenosis and other complications.

PMID- 19101897
TI  - Mutations of RAS gene family in specimens of bladder cancer.
AB  - INTRODUCTION: Studies have shown different types of RAS mutations in human
      bladder tumors with a wide range of mutation frequencies in different patient
      populations. This study aimed to assess the frequency of specific-point mutations
      in the RAS gene family of a group of Iranian patients with bladder cancer.
      MATERIALS AND METHODS: We examined the tumor specimens of 35 consecutive patients
      with transitional cell carcinoma. The DNA samples were evaluated for the
      occurrence of HRAS, KRAS, and NRAS activation using a polymerase chain reaction
      restriction fragment length polymorphism technique. RESULTS: None of the patients
      had mutations in the RAS gene family "hot spots" including codons 12, 13, and 61.
      CONCLUSION: We failed to find RAS mutations in our bladder tumor samples. These
      observations may reflect the involvement of different etiological factors in the
      induction of bladder tumor of which RAS mutation might not be present in all
      populations.

PMID- 19101898
TI  - Urine concentration of nuclear matrix protein 22 for diagnosis of transitional
      cell carcinoma of bladder.
AB  - INTRODUCTION: The aim of this study was to determine the diagnostic value of
      urine nuclear matrix protein 22 (NMP22) level in detection of transitional cell
      carcinoma (TCC) of the bladder. MATERIALS AND METHODS: A total of 76 patients
      with newly-diagnosed or recurrent TCC and 75 controls without urinary tract
      disorders participated in this study. A urine sample was obtained for measurement
      of the NMP22 level using the enzyme-linked immunoabsorbent assay. The resulted
      values were evaluated in comparison with the results of pathologic examination.
      RESULTS: A total of 76 patients with TCC of the bladder and 75 volunteers without
      TCC were enrolled in the study. The mean level of urine NMP22 had an increasing
      trend associated with tumor grade (P = .01) and tumor stage (P < .001). In
      participants without TCC, the mean urinary NMP22 level was 5.48 +/- 6.34 U/mL,
      while this value was 25.01 +/- 35.33 U/mL in patients with TCC of the bladder (P
      < .001). The sensitivity, specificity, positive predictive value, negative
      predictive value, and accuracy of urine NMP22 for detection of TCC were 75.5%,
      86.7%, 85.1%, 77.4%, and 80.8%, respectively. The sensitivity of NMP22 in
      detecting stage Ta tumors appeared to be low (31.3%), but for grade 1 tumors, the
      sensitivity was 66.7%. CONCLUSION: Measurement of urine NMP22 is a noninvasive,
      highly sensitive, and specific method for detecting TCC of the bladder and
      estimating its grade and stage. Further studies can be helpful to determine
      whether it can be used in clinical practice.

PMID- 19101899
TI  - Outcome of kidney transplantation in type 1 and type 2 diabetic patients and
      recipients with posttransplant diabetes mellitus.
AB  - INTRODUCTION: We aimed to assess the effects of different types of diabetes
      mellitus (DM) on patients receiving living donor kidney allografts. MATERIALS AND
      METHODS: A total of 111 kidney transplant patients with DM and 111 randomly
      selected kidney transplant recipients without DM were enrolled in the study. The
      characteristics of the kidney allograft recipients and the allograft and patient
      outcomes were assessed and compared between 4 groups of kidney recipients without
      DM and patients with type 1 DM, type 2 DM, and posttransplant DM. RESULTS: Of the
      111 patients with DM, 36 (32.4%), 20 (18.0%), and 55 (49.6%) had been diagnosed
      with type 1 DM, type 2 DM, and posttransplant DM, respectively. Diabetic patients
      had significantly higher rates of rejection episodes (P = .049) and suffered more
      frequently from delayed graft function (P = .03) compared to the kidney
      recipients in the control group. Patient and allograft survival rates were
      significantly lower in the patients with DM (regardless of their DM type)
      compared to the nondiabetic patients (P = .03 and P = .04, respectively).
      Prominently, type 1 DM had significantly adverse effects on patient and allograft
      survival. Patients with posttransplant DM had a relatively better patient
      survival compared to those with type 1 DM and type 2 DM. CONCLUSION: We found
      that kidney recipients with DM, especially preexisting DM, had worse patient and
      graft survival rates compared to the nondiabetics. These findings suggest that
      kidney transplant patients presenting with any type of DM should be more closely
      followed.

PMID- 19101900
TI  - Effect of saffron on semen parameters of infertile men.
AB  - INTRODUCTION: We conducted this study to determine the effects of saffron (Crocus
      sativus) on the results of semen analysis in men with idiopathic infertility.
      MATERIALS AND METHODS: In this clinical trial, 52 nonsmoker infertile men whose
      problem could not be solved surgically were enrolled. They were treated by
      saffron for 3 months. Saffron, 50 mg, was solved in drinking milk and
      administered 3 times a week during the study course. Semen analysis was done
      before and after the treatment and the results were compared. RESULTS: The mean
      percentage of sperm with normal morphology was 26.50 +/- 6.44% before the
      treatment which increased to 33.90 +/- 10.45%, thereafter (P < .001). The mean
      percentage of sperm with Class A motility was 5.32 +/- 4.57% before and 11.77 +/-
      6.07% after the treatment (P < .001). Class B and C motilities were initially
      10.09 +/- 4.20% and 19.79 +/- 9.11% which increased to 17.92 +/- 6.50% (P < .001)
      and 25.35 +/- 10.22% (P < .001), respectively. No significant increase was
      detected in sperm count; the mean sperm count was 43.45 +/- 31.29 x 106/mL at
      baseline and 44.92 +/- 28.36x 106/mL after the treatment period (P = .30).
      CONCLUSION: Saffron, as an antioxidant, is positively effective on sperm
      morphology and motility in infertile men, while it does not increase sperm count.
      We believe further studies on larger sample sizes are needed to elucidate the
      potential role and mechanism of action of saffron and its ingredient in the
      treatment of male infertility.

PMID- 19101901
TI  - Sexual dysfunction in aging men with lower urinary tract symptoms.
AB  - INTRODUCTION: Our aim was to evaluate the relationship between lower urinary
      tract symptoms (LUTS), age, and sexual dysfunction in the Iranian men aged 50 to
      80 years. MATERIALS AND METHODS: A total of 357 men aged 50 to 80 years
      presenting at the urological clinic were enrolled in this study. The
      International Prostatic Symptom Score (IPSS) and the International Index of
      Erectile Function (IIEF) questionnaires were used to assess the LUTS and sexual
      function, respectively. The questionnaires were completed by face-to-face
      interview. Logistic regression model was used for multivariate analysis of the
      risk factors of sexual dysfunction and its domains assessed by the IIEF. RESULTS:
      Of the patients, 332 (93%) were sexually active with a median sexual attempts of
      4.6 times per month. Frequency of sexual attempts was inversely related to LUTS
      severity (P < .001). Advanced age was positively associated with LUTS severity (r
      = 0.534, P < .001). Sexual dysfunction, defined as IIEF score of 20 and less, was
      present in 68.2% of the patients. All IIEF domain scores and the overall score
      were correlated with age (P < .001) and the IPSS (P < .001). In a multivariate
      analysis, age, diabetes mellitus, and the IPSS were strong independent predictors
      of the overall IIEF score. CONCLUSION: Sexual activity as an important component
      of the quality of life continues in the majority of men over 50 years. However,
      their sexual function can be severely affected by LUTS and its severity.

PMID- 19101902
TI  - Clean intermittent catheterization with triamcinolone ointment following internal
      urethrotomy.
AB  - INTRODUCTION: Our aim was to evaluate clean intermittent catheterization (CIC)
      results in combination with triamcinolone ointment for lubrication of the
      catheter after internal urethrotomy. MATERIALS AND METHODS: Seventy patients who
      underwent internal urethrotomy were assigned into 2 groups and performed CIC with
      either triamcinolone 1% ointment or a water-based gel (control) for lubrication
      of the catheter. They continued CIC regimen up to 6 month and were followed up
      for 12 months. Retrograde urethrography and urethrocystoscopy were done 6 and 12
      months postoperatively. In case of obstructive symptoms or any difficulty in
      passing the urethral catheter, internal urethrotomy would be performed, if
      needed, and the same follow-up protocol would be started again. The recurrence
      rates after the first and second urethrotomy attempts were compared between the
      two groups. RESULTS: Thirty patients in the triamcinolone group and 34 in the
      control group completed the study. There were no significant differences in the
      baseline characteristics of the patients or the etiology of the stricture between
      the two groups. There was a 30.0% recurrence rate in the patients of the
      triamcinolone group versus 44.1% in those of the control group after the first
      internal urethrotomy (P = .24). Following the second internal urethrotomy, the
      urethra was stabilized in 88.9% of the patients in the triamcinolone group and
      60.0% those in the control group (P = .15). CONCLUSION: Administration of
      triamcinolone ointment in patients on CIC regimen after internal urethrotomy only
      slightly decreased the stricture recurrence rate, and its possible effects should
      be more investigated.

PMID- 19101903
TI  - Conservative management of early bladder rupture after postoperative radiotherapy
      for prostate cancer.

PMID- 19101904
TI  - An unusual case of Birt-Hogg-Dube syndrome with renal involvement.

PMID- 19101905
TI  - True hermaphrodism presenting as pelvic abscess.

PMID- 19101906
TI  - Vanishing shaft of a double-j stent.

PMID- 19101907
TI  - Persistent multiple vesicocutaneous fistulas or watering-can abdomen.

PMID- 19101908
TI  - Avicenna's Canon of Medicine and Modern Urology: part I: bladder and its
      diseases.
AB  - Studying the Avicenna's Canon of Medicine, provides noteworthy information on the
      subjects related to urology. Some examples of these amazing items have been
      confirmed by the modern urology: explaining the 2-stage function of the bladder
      (filling and emptying stages); indirect pointing to a scientific law, named later
      as the Laplace's law, which is applicable to bladder physiology and explains
      intravesical pressure stability; describing the bladder layers and strength of
      the urothelial layer, which was later proved to be due to the tight junctions;
      describing the intramural ureter and its antireflux mechanism; scientific
      classifying the urethral and bladder diseases; and describing meticulously the
      semiology and epidemiology of bladder calculi. Avicenna has also pointed to
      inversion therapy in the treatment of urinary calculi, grating sign in bladder
      calculi, manipulation methods for treatment of bladder calculi, and finally, the
      Crede maneuver. His methodology is completely scientific, based on experiments
      and truly a basis of the modern medicine. This article is a review of Avicenna's
      views in medicine and their comparison with the modern urology.

PMID- 19101911
TI  - Notice of inadvertent duplicate publications.

PMID- 19101912
TI  - Graft fibrosis after pediatric liver transplantation: ten years of follow-up.
AB  - Previously we reported the presence of portal fibrosis in 31% (n = 84) of the
      grafts in protocol biopsies 1 year after pediatric liver transplantation (LTx).
      To assess the natural history of graft fibrosis after pediatric liver
      transplantation, we extended the analysis of graft histology in follow-up
      protocol biopsy specimens obtained 5 and 10 years after transplantation. We
      correlated histological results with clinical parameters at the time of LTx and
      during follow-up, to allow identification of risk factors for the development of
      fibrosis. From 1 year to 5 years after LTx, the prevalence of fibrosis increased
      from 31% to 65% (n = 66) but remained stable thereafter (at 10 years, 69%, n =
      55). At 10 years after LTx, however, the percentage of patients with severe
      fibrosis had increased from 10% (at 5 years) to 29%. Of the 69% of children
      without fibrosis at 1 year post-transplantation, 64% (n = 39) had developed some
      degree of fibrosis at 10 years. Fibrosis was strongly related to transplant
      related factors such as prolonged cold ischemia time, young age at the time of
      transplantation, high donor/recipient age ratio, and the use of partial grafts (P
      < 0.05). Fibrosis was not significantly related to rejection, chronic hepatitis,
      or the nature of the immunosuppressive therapy. CONCLUSION: Biopsies after
      pediatric LTx show that most grafts developed fibrosis within 5 years. At 10
      years after LTx, the graft fibrosis had progressed to severe fibrosis in at least
      25% of the patients. Development of fibrosis, starting either before or after the
      first year post-LTx, was strongly related to transplant-related factors,
      indicating the importance of these factors to long-term graft prognosis.

PMID- 19101913
TI  - Refolding and purification of rhNTA protein by chromatography.
AB  - RhNTA protein is a new thrombolytic agent which has potential medicinal and
      commercial value. Protein refolding is a bottleneck for large-scale production of
      valuable proteins expressed as inclusion bodies in Escherichia coli. The
      denatured rhNTA protein was refolded by an improved size-exclusion chromatography
      refolding process achieved by combining an increasing arginine gradient and a
      decreasing urea gradient (two gradients) with a size-exclusion chromatography
      refolding system. The refolding of denatured rhNTA protein showed that this
      method could significantly increase the activity recovery of protein at high
      protein concentration. The activity recovery of 37% was obtained from the initial
      rhNTA protein concentration up to 20 mg/mL. After refolding by two-gradient size
      exclusion chromatography refolding processes, the refolded rhNTA was purified by
      ion-exchange and affinity chromatography. The purified rhNTA protein showed one
      band in SDS-PAGE and the specific activity of purified rhNTA protein was 110,000
      U/mg.

PMID- 19101914
TI  - Keratan sulfate-containing proteoglycans in sheep brain with particular reference
      to phosphacan and synaptic vesicle proteoglycan isoforms.
AB  - Proteoglycans (PGs) are widely expressed in all areas of the brain. In this
      study, the keratan sulfate-containing PGs (KS-PGs) from cerebrum (CB), cerebellum
      (CL) and brainstem (BS) of young sheep brain were isolated, purified and
      characterized. The amount of KS-PGs in CL was significantly lower than that in CB
      and BS. KS-PGs were characterized by increased extent of glycosylation and
      heterogeneity of KS chains in CL. Western blot analyses demonstrated the presence
      of the KS-PGs phosphacan, SV2A and SV2B isoforms of synaptic vesicle proteoglycan
      in all three areas of the young sheep brain. Phosphacan predominated in BS and
      CB, showing significant molecular heterogeneity. SV2A and SV2B were found in two
      forms of high and low molecular sizes according to their extent of glycosylation
      in sheep brain. SV2A predominated in CL, where forms with very high molecular
      sizes were detected. Immunohistochemical examination revealed that SV2A was
      localized in the extracellular matrix of both gray and white matter. In contrast,
      phosphacan and SV2B were mainly localized in the white matter in all brain
      regions. The results of the present study demonstrated that KS-PGs are present in
      the three areas of the sheep brain, showing significant variations in their
      content, structure and localization among the distinct areas. These differences
      may be important for the physiology of the brain.

PMID- 19101915
TI  - Determination of urinary androgen glucuronides by capillary electrophoresis with
      electrospray tandem mass spectrometry.
AB  - Capillary electrophoresis-electrospray tandem mass spectrometry (CE-ESI/MS/MS) is
      a simple and highly sensitive method for quantifying seven urinary androgen
      glucuronides. The urine samples were diluted and filtered through a membrane
      filter, and the filtrate was injected into a CE-MS/MS system without further
      sample preparation steps such as extraction and derivatization. The calibration
      ranges were 0.01-5 microg/mL for glucuronides of androsterone and 11beta-OHAn-3G,
      and 5-500 ng/mL for glucuronides of 11-ketoAn, DHEA, testosterone,
      epitestosterone and DHT. The linearity of the method was 0.992-0.998, and the
      limits-of-detection at a signal-to-noise ratio of 3 were 5-10 ng/mL. The
      coefficients of variation were in the range of 4.0-9.0% for intra-day assay and
      4.1-9.8% for inter-day assay. The proposed method may be applicable to metabolic
      profiling in both quantitative and qualitative analysis.

PMID- 19101916
TI  - Drug information for patients--an update of long-term results: type of enquiries
      and patient characteristics.
AB  - PURPOSE: To analyse the type of enquiries to a drug information service in
      Germany, available exclusively for patients. METHODS: Sociodemographic
      characteristics of the patients who used the service, number and kind of drugs
      taken, existing diseases, reasons for enquiry as well as type of answers provided
      were recorded. For the present evaluation we analysed all enquiries to the
      service from August 2001 to January 2007. RESULTS: A total of 5587 enquiries were
      received. 5013 enquiries from 4091 patients were available for further analysis
      in detail. The patient group using the service most frequently were women between
      61 and 70 years (23.3%). 1457 enquiries (29.1%) were made by patients who had
      contacted the information service once or several times before. The group of
      drugs most often asked about were cardiovascular drugs (33.4%), followed by drugs
      for the nervous system (16.2%) and for the alimentary tract and metabolism
      (12.4%). On average, each patient had questions about 2.6 (median 1; 1-22) drugs
      simultaneously. Common reasons for contacting the service were adverse drug
      reactions (22.1%), the need for general information about the drug (19.9%),
      information about therapy (12.4%) and drug interactions (10.2%). CONCLUSIONS: A
      lot of patients need additional information about their medication, especially
      concerning drug groups that are frequently prescribed. The presented drug
      information service can be one helpful tool to counteract these information
      deficits and to increase patients' knowledge about their drugs.

PMID- 19101917
TI  - Rapid analysis of tetracaine for a tape stripping pharmacokinetic study using
      short-end capillary electrophoresis.
AB  - A rapid and simple short-end (reverse) capillary zone electrophoresis method was
      developed and validated for the separation and quantification of tetracaine in
      skin using tape samples. The separation was performed in a 485 mm (400 mm to
      window) x 50 microm internal diameter fused silica capillary using a background
      electrolyte of phosphoric acid-Tris pH2.5 at -25 kV. The extraction of tetracaine
      from tape samples was achieved using methanol diluted to 50% with water before
      injection. Procaine was the internal standard. The migration times for procaine
      and tetracaine were 1.25 and 1.36 min, respectively. The limit of quantification
      for tetracaine was 50 microg, with a signal-to-noise ratio greater than 10. The
      calibration curve was linear from 50 to 1200 microg with r(2) greater than 0.99.
      The CV for both within- and between-assay imprecision and the percentage
      inaccuracy for the quality control samples including lower and upper limits of
      quantitation were <12.1% and <11%, respectively. The absolute mean recovery of
      tetracaine was >97%. The accuracy and selectivity of this method allowed the
      rapid measurement of tetracaine in tape samples obtained from a skin tape
      stripping study of local anaesthetics in healthy subjects.

PMID- 19101918
TI  - Highly sensitive method for the determination of ropinirole with a lower limit of
      quantitation of 3.45 pg/mL in human plasma by LC-ESI-MS/MS: application to a
      clinical pharmacokinetic study.
AB  - A highly sensitive, rapid assay method has been developed and validated for the
      estimation of ropinirole (RPR) in human plasma with liquid chromatography coupled
      to tandem mass spectrometry with electrospray ionization in the positive-ion
      mode. A solid-phase process was used to extract RPR and citalopram (internal
      standard, IS) from human plasma. Chromatographic separation was operated with
      0.2% ammonia solution:acetonitrile (20:80, v/v) at a flow rate of 0.50 mL/min on
      a Hypurity C(18) column with a total run time of 3.2 min. The MS/MS ion
      transitions monitored were 261.2 --> 114.2 for RPR and 325.1 --> 209.0 for IS.
      Method validation and clinical sample analysis were performed as per FDA
      guidelines and the results met the acceptance criteria. The lower limit of
      quantitation achieved was 3.45 pg/mL and the linearity was observed from 3.45 to
      1200 pg/mL. The intra-day and inter-day precisions were in the range of 4.71-7.98
      and 6.56-8.31%, respectively. This novel method has been applied to a
      pharmacokinetic study of RPR in humans.

PMID- 19101919
TI  - Adverse drug reactions in patients in an Iranian department of internal medicine.
AB  - PURPOSE: Adverse drug reactions (ADRs) are a major cause of hospital admission
      and inpatient morbidity. The department of internal medicine is not an exception
      to this issue. This study was performed to determine the nature and frequency of
      ADRs in an internal medicine ward in Iran. METHODS: This survey was a prospective
      observational study based on admissions of 400 patients to the internal medicine
      ward over a 15-week period. Patients were intensively followed in order to assess
      any ADR as a cause of admission or occurring during hospitalization. Any
      suspicious ADR was confirmed by a pharmacist/pharmacologist. RESULTS: There were
      47 patients of 400 patients (11.75%) that experienced at least one ADR. ADR
      leading to the admission was seen in seven cases (1.75%) and in 40 (10%) it
      occurred during hospitalization. ADRs were identified as preventable reactions in
      50% of cases and as predictable in 94.3%. The severity of 18.6% of the ADRs was
      identified as mild, 62.9% as moderate, 14.3% as severe and 4.3% as lethal.
      Gastrointestinal system disorders (44.3%) represented the most frequent ADRs. The
      therapeutic groups that most commonly associated with suspected ADRs were
      antineoplastic, immunosuppressive and medicines used in palliative care (54.8%).
      CONCLUSIONS: ADRs are common among hospitalized patients in department of
      internal medicine and can be severe and even lethal. Since most ADRs occurred
      during hospitalization in studied patients and half of them were preventable,
      prevention strategies should be considered in hospitals. Also, our findings
      confirmed the role of hospital pharmacists in the reducing ADRs.

PMID- 19101920
TI  - Fear of recurrence and psychological distress in head and neck cancer patients
      and their carers.
AB  - BACKGROUND: Fear of recurrence (FOR) has been increasingly recognised as an issue
      of significant burden for most cancer patients, and has been associated with
      psychological morbidity and reduced quality of life. More recently, the impact of
      recurrence fears has been indicated in the families of cancer patients. However,
      there has been a lack of prospective research. AIM: To systematically examine
      distress and illness concerns among patient-carer dyads. METHODS: A multi-centre
      prospective study of head and neck cancer patients and their carers (patients,
      n=101; carers, n=101), surveyed at two time-points following diagnosis. RESULTS:
      Carers recorded higher recurrence concerns on average than the patient group
      (p<0.001). A predictive path model of patient and carer self-reports of distress
      and FORs was explored, with an excellent overall fit of the final model
      (chi(2)=15.4, df=12, p=0.22, Comparative Fit Index (CFI)=0.994, Root Mean Square
      Estimate of Approximation (RMSEA)=0.053). CONCLUSIONS: The preliminary results
      establish that early fears and distress within individuals govern later reports
      on these same attributes, but that there is some weak evidence of influence from
      one attribute to another within and across individuals in the dyad. Future
      prospective dyadic research is warranted to ascertain the level of these fears
      over an extended time and their relationship to patient and carer adaptation.
      Intervention may be needed to reduce this disease concern to a manageable level
      at an early stage of the illness trajectory.

PMID- 19101921
TI  - Befriending carers of people with dementia: a cost utility analysis.
AB  - OBJECTIVE: There is very little evidence on the cost-effectiveness of social care
      interventions for people with dementia or their carers. The BEfriending and Costs
      of CAring trial (BECCA, ISRCTN08130075) aimed to establish whether a structured
      befriending service improved the quality of life of carers of people with
      dementia, and at what cost. METHODS: We performed an economic evaluation
      alongside a single blind, randomised controlled trial in a community setting of
      236 carers of people with a primary progressive dementia. The intervention was
      contact with a Befriender Facilitator (BF), and offer of match with a trained lay
      volunteer befriender compared with no BF contact. Main outcome measures were
      health and social care, voluntary sector, and family care costs and quality
      adjusted life years (QALYs) in carers over 15 months. RESULTS: Mean QALYs per
      carer over 15 months were 0.017 higher in the intervention group compared with
      control (95%CI: -0.051, 0.083). Mean costs from a societal perspective were pound
      1,813 higher (- pound 11,312, pound 14,984). The point estimate Incremental Cost
      Effectiveness Ratio (ICER) is thus pound 105,954 per incremental QALY gained.
      Probabilistic sensitivity analysis suggests a 42.2% probability that the ICER is
      below pound 30,000 per QALY. Inclusion of dementia patient QALYs reduces the ICER
      to pound 28,848 (51.4% probability below pound 30,000). CONCLUSIONS: Befriending
      leads to a non-significant trend towards improved carer quality of life, and
      there is a non-significant trend towards higher costs for all sectors. It is
      unlikely that befriending is a cost-effective intervention from the point of view
      of society.

PMID- 19101922
TI  - Ultratrace analysis of uracil and 5-fluorouracil by molecularly imprinted polymer
      brushes grafted to silylated solid-phase microextraction fiber in combination
      with complementary molecularly imprinted polymer-based sensor.
AB  - Main inborn errors of metabolism diagnosable through uracil (Ura) analysis and
      the therapeutic monitoring of toxic 5-fluorouracil (5FU) in dihydro pyrimidine
      dehydrogenase (DPD) deficient patients require a sensitive, reproducible,
      selective and accurate method. In this work, an artificial receptor in the format
      of molecularly imprinted polymer (MIP) brush 'grafted to' the surface of sol-gel
      immobilized on cost-effective homemade solid-phase microextraction (SPME) fibers,
      individually imprinted with either of Ura and 5FU, was used in combination with a
      voltammetric sensor duly modified with the same MIP. This combination provided up
      to 10- and 8.4-fold preconcentrations of Ura and 5FU, respectively, which was
      more than sufficient for achieving stringent detection limits in the primitive
      diagnosis of uracil disorders and fluoropyrimidine toxicity in DPD-deficient
      patients. The proposed method permits the assessment of Ura and 5FU plasma
      concentrations with detection limits pf 0.0245 and 0.0484 ng mL(-1) (RSD = 1.0
      2.5%, S/N = 3), respectively, without any problems of non-specific false
      positives and cross-reactivities in complicated matrices of biological samples.

PMID- 19101924
TI  - An introduction to epitope prediction methods and software.
AB  - In this paper, current prediction methods and algorithms for both T- and B cell
      epitopes are reviewed, and a comprehensive summary of epitope prediction software
      and databases currently available online is also provided. This review can offer
      researchers in this field a sense of direction and insights for future work.
      However, our main purpose is to introduce clinical and basic biomedical
      researchers who are not familiar with these biological analysis tools and
      databases to these online resources and to provide guidance on how to use them
      effectively.

PMID- 19101923
TI  - Rapid analysis of N-linked oligosaccharides in glycoproteins (ovalbumin,
      ribonuclease B and fetuin) by reversed-phase ultra-performance liquid
      chromatography with fluorescence detection and electrospray ionization time-of
      flight mass spectrometry.
AB  - Rapid, selective and sensitive determination of N-linked oligosaccharides in
      glycoproteins (ovalbumin, ribonuclease B and fetuin) was performed by ultra
      performance liquid chromatography (UPLC) with fluorescence (FL) and electrospray
      ionization time-of-flight mass spectrometry (ESI-TOF-MS). The asparaginyl
      oligosaccharide moiety was first liberated from each glycoprotein by pronase E (a
      proteolitic enzyme). The oligosaccharide fractions separated by gel-permeation
      chromatography were labeled with 1-pyrenesulfonyl chloride (PSC, a fluorescence
      reagent), separated by UPLC in a short run time, and then detected by FL and TOF
      MS. The PSC-labeled oligosaccharides were selectively identified from the FL
      detection and then sensitively determined by ESI-TOF-MS. As the results, 15,
      eight and four kinds of N-linked oligosaccharides were detected from ovalbumin,
      ribonuclease B and fetuin, respectively. Because the present method is rapid
      (within 9 min), selective and sensitive (approximate 60 fmol, S/N = 5), the
      determination of N-linked oligosaccharides in various glycoproteins seems to be
      possible.

PMID- 19101925
TI  - Rapid determination of rifaximin in rat serum and urine by direct injection on to
      a shielded hydrophobic stationary phase by HPLC.
AB  - A simple and rapid reversed-phase HPLC method for determination of rifaximin in
      rat serum and urine was developed. Separation of rifaximin from biological matrix
      was achieved by direct injection of rat serum and urine onto a restricted-access
      medium, Supelco LC-Hisep, a shielded hydrophobic stationary phase, using
      acetonitrile:water:acetic acid (18:82:0.1 v/v/v) as a mobile phase. The linear
      range was 0.10-20 microg/mL (r(2 )> 0.999, n = 6), intraday and interday
      variation was <6.10%. The limits of detection and quantification were 0.03
      (signal-to-noise ratio >3) and 0.10 microg/mL (signal-to-noise ratio >10),
      respectively. The method was successfully applied to pharmacokinetic studies of
      rifaximin after an oral administration to rats.

PMID- 19101926
TI  - Information and decision-making process for selective termination of dichorionic
      pregnancies: some French obstetricians' points of view.
AB  - BACKGROUND: In France, neither Bioethics Law nor law related to abortion make
      reference to selective terminations (ST). Because they apply in the context of
      multiple pregnancies, ST raises problems which differ from those we usually see
      in prenatal medicine.We wanted to know: 1) which approaches were used by
      obstetricians to inform couples about processes and risks of ST, 2) their role in
      the decision-making process of couples, and 3) their representations about the
      level of autonomy that couples are able to assume. METHODS: Qualitative research,
      eight semi-structured interviews performed with eight obstetricians from seven
      public hospitals in Parisian region. RESULTS: Similarities: *Necessity to devote
      a lot of time to information. *Importance to give the couples the maximum of time
      for reflection. *Belief that the final decision belongs to couples. Discordances:
      *Heterogeneity of revealed information. *Discrepancy in the will to assure a
      complete and non directive information transfer. *Divergence in representations
      of what is an ethical support. *Differences in the limits of the autonomy of
      couples. CONCLUSIONS: All physicians believe that they respect the autonomy of
      couples, arguing that final decision belongs to them. Paradoxically, some results
      are indicative of a sizeable level of directiveness from the physicians.

PMID- 19101927
TI  - Dodging matrix effects in liquid chromatography tandem mass spectrometric assays-
      compilation of key learnings and perspectives.
AB  - Triple quad liquid chromatography mass spectrometric assays (LC/MS/MS) have
      revolutionized the analysis of drug(s)/metabolite(s) with exceptional speed,
      sensitivity and selectivity features. From inception to date, several new and
      innovative features have been regularly proposed by researchers to further
      enhance the value in the applicability of this analytical tool. However, owing to
      such compressed run times and scanty sample preparation procedures, LC/MS/MS
      assays that are not fully optimized generally have issues of matrix effects,
      where ionization potential is either suppressed or enhanced due to the presence
      of other materials (endogenous/exogenous) in the matrix. By definition, even co
      medications, isomeric or isobaric impurities, and drug excipients used in dosing
      solutions could also potentially contribute to matrix effects. This article
      captures some of the interesting work carried out by researchers to understand
      and handle matrix effects. Additionally, it provides perspectives to effectively
      deal with matrix effects.

PMID- 19101928
TI  - Application of column-switching HPLC method in evaluating pharmacokinetic
      parameters of zaltoprofen and its salt.
AB  - The objective of this study was to compare the pharmacokinetic parameters of
      zaltoprofen and those of its sodium salt in rats. Zaltoprofen, a potent non
      steroidal anti-inflammatory agent, was virtually insoluble in water, but its
      sodium salt had excellent water solubility. To investigate the effect of aqueous
      solubility differences upon their pharmacokinetic parameters, minicapsules
      containing the drug powders were administrated orally to rats, and blood samples
      were taken via the common carotid artery. A column-switching high-performance
      liquid chromatographic analytical procedure was developed and validated for the
      quantitation of zaltoprofen in rat plasma samples. Our study demonstrated that
      the time required to reach maximum plasma concentration (T(max)) of zaltoprofen
      sodium was significantly reduced and its maximum plasma concentration (C(max))
      was increased 1.5-fold, relative to the values for zaltoprofen. It is anticipated
      that the sodium salt of zaltoprofen will allow the rapid onset of the drug's
      action in the treatment of inflammatory diseases.

PMID- 19101930
TI  - Recent progress in analytical capillary ITP.
AB  - ITP is an electrophoretic technique that has been attracting constant attention
      for many years due to its pronounced capability to concentrate trace analytes by
      several orders of magnitude. In practice, it is used predominantly in capillary
      format, where the capillaries used have id ranging between 0.02 and 0.8 mm. The
      volumes of the samples introduced may be up to several tens of microliters and
      trace analytes diluted in such a volume are concentrated into zones having
      volumes in the range of picoliters. Moreover, it offers simultaneously efficient
      separation of the analytes. That is why ITP retains its important position in
      many current multistage and multidimensional separation schemes where it is used
      always as the starting step that brings preseparation and concentration of sample
      components. This article links up previous reviews on the topic and summarizes
      the progress of analytical capillary ITP since 2006; 90 reviewed papers include
      theory and methodological novelties as well as analytical applications. Papers
      using ITP as part of multistage separation schemes are also included.

PMID- 19101929
TI  - Transport behavior of ellagic acid of pomegranate leaf tannins and its
      correlation with total cholesterol alteration in HepG2 cells.
AB  - The aim of this study was to investigate whether ellagic acid in pomegranate leaf
      tannins could be transported into HepG2 cells and its transport behavior. High
      performance liquid chromatography coupled with a 996 photodiode array detector at
      254 nm was applied. The mobile phase was an acetonitrile-water solution
      (containing 0.1% triethylamine, pH 3.0; 16:64, v/v, for determining ellagic acid
      in cells). The flow rate was 0.8 mL/min. Cells were incubated with pomegranate
      leaf tannins with 100 and 50 microg/mL (containing 1.71 and 0.85 microg/mL of
      ellagic acid, respectively) for a specific time, then lysed and sonicated in
      methanol to extract intracellular ellagic acid. A 10 microL aliquot of sample was
      injected into the HPLC system to determine ellagic acid concentration. The
      results showed that ellagic acid in pomegranate leaf tannins could be transported
      into the cells, which was in correlation with total cholesterol alteration in the
      cells. This is the first time that the transport behavior of ellagic acid through
      HepG2 cells in vitro has been comprehensively demonstrated.

PMID- 19101931
TI  - Contemporary sample stacking in CE.
AB  - Sample stacking techniques remain an important tool for enhancement of the
      selectivity and sensitivity of analyses in contemporary CZE. This contribution
      reviews new knowledge on this topic published since 2006. It is organized
      according to the operational principles used, which include concentration
      adjustment, application of a pH step, MEKC and sweeping, and transient ITP.
      Techniques combining several of these principles and comparative studies are also
      included.

PMID- 19101932
TI  - Ten years of axial capacitively coupled contactless conductivity detection for
      CZE--a review.
AB  - Contactless conductivity detection is universal for CE in that all charged
      species can be quantified, and it is particularly attractive for those inorganic
      and organic ions that are not directly accessible by optical means. It is not
      necessary to make precise alignments or to create an optical window into the
      capillary. Commercial detectors that can be retrofitted to existing instruments
      are available at a cost that is lower than that of any other electrophoresis
      detector. The approach is also suited for lab-on-chip devices. It is attempted in
      this review to summarize some of the expertise accumulated since the introduction
      of the axial contactless conductivity detector to CE 10 years ago.

PMID- 19101933
TI  - Virus analysis using electromigration techniques.
AB  - We discuss the progress during the last 4 years in the analysis of viruses by
      electrophoresis in capillaries and microfluidic devices. The paper is the
      continuation of a review published in this journal in 2005 [Kremser, L., Blaas,
      D., Kenndler, E., Electrophoresis 2004, 25, 2282-2291]. Eighteen papers on the
      topic have appeared since; the majority deals with zone electrophoresis and three
      reports are on IEF. These methods have been applied to human rhinoviruses,
      poliovirus Semliki Forest virus, norovirus-like particles, and the two
      bacteriophages MS2 and T5. A main finding was that addition of detergents and
      salts to the BGEs are essential for the robustness of the CE analysis. Analyte
      detection was usually via UV absorbance but there are some examples where the
      viruses were rendered fluorescent via modification of the capsid proteins with
      reactive dyes and/or by non-covalent attachment of intercalating fluorescent
      compounds to the nucleic acids making up the viral genome. Interestingly, some
      viruses are permeable to small molecular mass components; this allows fluorescent
      dyes to diffuse into the intact virus where they attach to the nucleic acid.
      Release of a viral genome upon heating was also monitored by using similar
      methodologies. Interactions of viruses and subviral particles with antibodies,
      receptors, and receptor-decorated liposomes were investigated with CE methods,
      all by using a non-equilibrium approach (i.e. co-incubation of the components
      prior to CE separation). Viruses are multivalent (i.e. possess many identical
      surface-exposed patches) and most of them are composed of defined numbers of
      identical subunits. The high resolution of CE has been most remarkably
      demonstrated by the separation of stoichiometric complexes between virus and a
      distinct number of soluble recombinant receptors and revealed their concentration
      dependent distribution.

PMID- 19101934
TI  - Liquid-phase-based separation systems for depletion, prefractionation and
      enrichment of proteins in biological fluids for in-depth proteomics analysis.
AB  - This review article is concerned with (i) proteomic sample preparation including
      among other things the depletion of high-abundance proteins and the concentration
      of low-abundance proteins and (ii) their subsequent prefractionation for further
      analysis. Subjects (i) and (ii) are essentials for in-depth proteomic analysis by
      multidimensional liquid-phase separation techniques (e.g. multidimensional
      electrophoresis and LC in various formats) followed by mass spectrometric
      identification and bioinformatic. More than 90 papers published in the period
      covering early 2000 to the present have been reviewed. It should be noted that
      this review article is by no means exhaustive, and the aim was to rather provide
      a concise description of the latest developments in the field.

PMID- 19101936
TI  - Photodynamics of a PV trimer in high-viscosity solvents and in PMMA films: a new
      insight into energy transfer versus conformational relaxation in conjugated
      polymers.
AB  - Non-Stokes-Einstein relaxation: The rate constant of conformational relaxation of
      a phenylenevinylene trimer (see picture) in different solvents is proportional to
      eta(-alpha), with alpha values decreasing from close to unity (low viscosity) to
      zero at sufficiently high solvent viscosity. This behaviour is attributed to the
      flexible methylbutyl side chains of the trimer, which partially screen the
      solvent friction. The p-phenylenevinylene (PV) trimer (MBOPV3) was used to probe
      the effect of conformational relaxation on fluorescence decays of PV-based
      polymers in the high solvent viscosity regime, from n-hexadecane (3.45 cP at 293
      K) to liquid paraffin (123 cP at 293 K), and in dilute poly(methyl methacrylate)
      (PMMA) solid films. The effect of intermolecular energy transfer and radiative
      transport on the fluorescence decays was also analysed by increasing the
      concentration of MBOPV3 in the PMMA films up to a pure MBOPV3 film. The rate
      constant of conformational relaxation was found to decrease with increasing
      solvent viscosity up to about 23 cP, but then becomes viscosity independent. The
      non-Stokes-Einstein behaviour of k(CR) versus eta over the whole viscosity range
      apparently results from the presence of the flexible methylbutyl side chains of
      MBOPV3, which partially screens the solvent friction. Conformational relaxation
      is not observed in very dilute PMMA solid films, where the fluorescence decay
      becomes single exponential. The decays become multi-exponential again with an
      increase of MBOPV3 concentration in the PMMA films, but in this case it is due to
      intermolecular (interchain) energy transfer from less planar to more planar
      conformations of MBOPV3. In the pure MBOPV3 film, interchain energy transfer
      (radiative and non-radiative) is the major process responsible for the observed
      (tetra-exponential) decays.

PMID- 19101937
TI  - Heterogeneous photochemistry relevant to the troposphere: H(2)O(2) production
      during the photochemical reduction of NO(2) to HONO on UV-illuminated TiO(2)
      surfaces.
AB  - Bleached out: The detection of an oxidized co-product, hydrogen peroxide, during
      an important tropospheric reaction, combined with the detection of
      photoaccelerated surface nitrate formation (a competing pathway), allows a likely
      mechanism to be proposed (see figure) which explains previously observed
      experimental stoichiometries.

PMID- 19101935
TI  - Estimating diagnostic accuracy of multiple binary tests with an imperfect
      reference standard.
AB  - The goal in diagnostic medicine is often to estimate the diagnostic accuracy of
      multiple experimental tests relative to a gold standard reference. When a gold
      standard reference is not available, investigators commonly use an imperfect
      reference standard. This paper proposes methodology for estimating the diagnostic
      accuracy of multiple binary tests with an imperfect reference standard when
      information about the diagnostic accuracy of the imperfect test is available from
      external data sources. We propose alternative joint models for characterizing the
      dependence between the experimental tests and discuss the use of these models for
      estimating individual-test sensitivity and specificity as well as prevalence and
      multivariate post-test probabilities (predictive values). We show using
      analytical and simulation techniques that, as long as the sensitivity and
      specificity of the imperfect test are high, inferences on diagnostic accuracy are
      robust to misspecification of the joint model. The methodology is demonstrated
      with a study examining the diagnostic accuracy of various HIV-antibody tests for
      HIV.

PMID- 19101938
TI  - How does your MOF grow?
AB  - Metal-organic frameworks (MOFs) are one of the most important classes of material
      in current chemistry. One open question is what is the mechanism of their crystal
      growth? In situ atomic force microscopy (see image) can be used to look at the
      surface of crystals as they grow, revealing a number of interesting features and
      giving clues to the molecular species that are important in the growth mechanism.

PMID- 19101939
TI  - Chiral guanidine catalyzed enantioselective reactions.
AB  - Chiral guanidine catalysts share common characteristics such as high pK(a) values
      and dual hydrogen-bonding modes of activation, and high catalytic activities and
      enantioselectivities can often be achieved. The utilization of guanidines as
      catalysts has been growing at a steady pace. In the past few years, it has
      attracted tremendous attention through several landmark achievements. This
      article highlights the development of chiral guanidine catalysis in asymmetric
      synthesis.

PMID- 19101940
TI  - Transition-metal-catalyzed enantioselective [2+2+2] cycloadditions for the
      synthesis of axially chiral biaryls.
AB  - Recent advances towards a development of novel transition-metal-catalyzed
      enantioselective [2+2+2] cycloadditions for the synthesis of axially chiral
      biaryls are reviewed. A number of efficient enantioselective biaryl syntheses
      were accomplished by chiral cobalt(I), iridium(I), and rhodium(I) complex
      catalyzed [2+2+2] cycloadditions. Furthermore, the enantioselective synthesis of
      axially chiral biaryls possessing non-biaryl axial chirality was also developed
      by using chiral rhodium(I) complexes as catalysts.

PMID- 19101941
TI  - A practical approach for ambient-pressure hydrogenations using Pd on porous
      glass.
AB  - A Pd on porous glass catalyst system was used in the liquid-phase hydrogenation
      of terpenoid substrates with dihydrogen at room temperature and atmospheric
      pressure. A multitude of substances were hydrogenated selectively with yields of
      90-100 %. In all experiments, only C--C, C--N, and N--N double bonds were
      hydrogenated. Studies revealed that carbonyl and aromatic double bonds are inert
      towards catalytic reduction with dihydrogen under the conditions employed. In
      some cases, hydrogenation was accompanied by isomerization, so that treatment of
      beta-pinene, for example, afforded isomeric alpha-pinene, which was subsequently
      hydrogenated to pinane.

PMID- 19101942
TI  - Reduction in delay time of high-dwell volume pumps in LC-MS applications using
      short-term low-ratio split flow.
AB  - We present a simple hardware design which reduces run time of gradient-based
      LC/MS applications and improves system equilibration. Our approach does not
      sacrifice efficiency of chromatographic separation, and does not affect analyte
      retention time and therefore does not require revalidation. Our technical design
      is based on a six-port/two-position switching valve and flow splitter installed
      prior to the LC column. This design minimizes time delays caused by the high
      dwell volume of some LC pumps. Implementation of short-term (40-55 s) low-ratio
      (1:10) flow splitting reduced delay times by over four-fold in our application.
      This approach allowed hardware-associated time delays to be minimized.
      Alternative plumbing suggestions are also discussed.

PMID- 19101943
TI  - Determination of artesunate using reversed-phase HPLC at increased temperature
      and ELSD detection.
AB  - Artesunate (ART) determination can be performed by evaporative light scattering
      detection with mobile phase composed of CH(3)CN/HCOOH 0.01 M (40:60 v/v; pH
      2.85). Evaporative light scattering detection instead of UV detection allowed to
      improve the sensitivity and the LOD. However, the evaporative light scattering
      detection response of dihydro-artemisinin appears weaker than for ART, whereas
      with UV detection the response of ART and dihydroartemisinin seemed similar.
      Constant analysis time was obtained on using the mobile phase with a flow rate of
      0.5 mL/min and column temperature at 60 degrees C instead of 0.7 mL/min at room
      temperature. This led to less solvent consumption. Moreover, decrease in the flow
      rate and increase in the column temperature were advantageous for higher
      sensitivity with both evaporative light scattering detection and UV detection.
      ART determination in rectal gel and suppositories were compared with these
      different detection modes and similar results were obtained.

PMID- 19101944
TI  - Enantioselective isolation of methyl jasmonate using permethyl-beta-cyclodextrin
      HPLC.
AB  - A method based on the use of HPLC for the enantioselective resolution of the four
      stereoisomers of methyl jasmonate (MJ) with no need for the previous formation of
      the diastereoisomers is developed. To that end, a Nucleodex-beta-PM column as
      well as an optimization process considering different flow rates and mobile phase
      compositions were required. As a result, 0.8 mL/min and 55:45 methanol/water
      composition were the conditions selected to carry out the separation of the
      stereoisomers. Isolation of pure (-)- and (+)-MJ was accomplished by collecting
      the HPLC fractions corresponding to their elution time. SPE was subsequently used
      to concentrate and change the solvent of the HPLC fractions collected. Chiral GC
      and polarimetry were additionally employed to evaluate the purity and optical
      rotation, respectively, of the enantiomers separated. The results found in this
      study are particularly relevant considering that MJ stereoisomers are not
      commercially available.

PMID- 19101945
TI  - Effect of stability of internal standard on quantification of 15 flavonoids in
      Epimedium using CZE.
AB  - A CZE method was developed for the simultaneous determination of 15 flavonoids,
      including epimedin B, epimedin A, hexandraside F, epimedin C, icariin,
      sagittatoside B, sagittatoside A, hexandraside E, 2''-O-rhamnosyl icariside II,
      baohuoside VII, baohuoside I, caohuoside C, epimedoside C, baohuoside II, and
      kaempferol-3-O-rhamnoside, in different species of Epimedium, and the effect of
      stability of internal standard (IS) on quantification was also investigated. As a
      result, rutin was not available for use as an IS because of its unstable property
      in sample solution, which suggested that the stability of IS both in standards
      and sample solution should be considered for the analysis. Using stable daidzein
      as IS, the analysis was performed within 35 min by using 50 mM borax buffer
      containing 20% ACN as a modifier (pH 10.0), while separation voltage was 25 kV
      and temperature was at 30 degrees C. The method was validated to be accurate,
      simple, and repeatable, and was successfully applied to the analysis of 36
      samples from 17 species of Epimedium.

PMID- 19101946
TI  - Quantitative capillary electrophoresis and its application in analysis of
      alkaloids in tea, coffee, coca cola, and theophylline tablets.
AB  - A quantitative CE (qCE) system with high precision has been developed, in which a
      4-port nano-valve was isolated from the electric field and served as sample
      injector. The accurate amount of sample was introduced into the CE system with
      high reproducibility. Based on this system, consecutive injections and
      separations were performed without voltage interruption. Reproducibilities in
      terms of RSD lower than 0.8% for retention time and 1.7% for peak area were
      achieved. The effectiveness of the system was demonstrated by the quantitative
      analysis of caffeine, theobromine, and theophylline in real samples, such as tea
      leaf, roasted coffee, coca cola, and theophylline tablets.

PMID- 19101947
TI  - International epidemiology of prostate cancer: geographical distribution and
      secular trends.
AB  - This review outlines current international patterns in prostate cancer incidence
      and mortality rates and survival, including recent trends and a discussion of the
      possible impact of prostate-specific antigen (PSA) testing on the observed data.
      Internationally, prostate cancer is the second most common cancer diagnosed among
      men (behind lung cancer), and is the sixth most common cause of cancer death
      among men. Prostate cancer is particularly prevalent in developed countries such
      as the United States and the Scandinavian countries, with about a six-fold
      difference between high-incidence and low-incidence countries. Interpretation of
      trends in incidence and survival are complicated by the increasing impact of PSA
      testing, particularly in more developed countries. As Western influences become
      more pronounced in less developed countries, prostate cancer incidence rates in
      those countries are tending to increase, even though the prevalence of PSA
      testing is relatively low. Larger proportions of younger men are being diagnosed
      with prostate cancer and living longer following diagnosis of prostate cancer,
      which has many implications for health systems. Decreasing mortality rates are
      becoming widespread among more developed countries, although it is not clear
      whether this is due to earlier diagnosis (PSA testing), improved treatment, or
      some combination of these or other factors.

PMID- 19101948
TI  - Traditional Japanese diet and prostate cancer.
AB  - The traditional Japanese diet has been suggested by some researchers to be
      associated with a decreased risk of prostate cancer (PCa). In this paper, we
      assumed the following three characteristics of the traditional Japanese diet high
      in soybean products, high in fish, and low in red meat. Isoflavones,
      polyunsaturated long chain (n - 3) fatty acids, and saturated fatty acids were
      thought to be micronutrients in biological etiology relevant to soybean products,
      fish, and red meat, respectively. Analytical epidemiological studies on the risk
      of PCa were identified using the MEDLINE database from 1998 to 2007. Some
      published studies showed a negative association of soybean products and
      isoflavones to PCa risk, an inverse association for fish or polyunsaturated long
      chain (n - 3) fatty acids such as eicosapentaenic acid (EPA) and docosahexaenoic
      acid (DHA) with PCa risk, and a positive association of red meat or saturated
      fatty acids with PCa risk, respectively. In conclusion, although it is possible
      that the traditional Japanese diet may reduce the risk of PCa through a
      combination of characteristics such as being high in soybean products, high in
      fish, and low in red meat, further well-designed epidemiological studies such as
      nested case-control studies with nutritional analyses of blood samples are needed
      to confirm this association.

PMID- 19101949
TI  - Winding up: rights and rights.

PMID- 19101950
TI  - Viewpoint: a viewpoint on viewpoints.

PMID- 19101951
TI  - The role of lymphadenectomy in esophageal cancer.
AB  - Lymph node metastases are common in esophageal cancer and are associated with a
      poor prognosis. Resection and examination of 15-18 lymph nodes is required for
      adequate staging of esophageal cancer. Improved survival is associated with
      involvement of five or fewer nodes or lymph node ratio (LNR) of < 0.10-0.20. More
      extensive lymph node dissection during esophagectomy offers improved staging but
      may also provide therapeutic benefit in terms of control of locoregional disease
      and possibly improved overall survival.

PMID- 19101952
TI  - Current controversies in prenatal diagnosis 2: Should laser ablation of placental
      anastomoses be used in all cases of twin to twin transfusion?

PMID- 19101953
TI  - PGD for monogenic disorders: aspects of molecular biology.
AB  - Preimplantation genetic diagnosis (PGD) for monogenic diseases has known a
      considerable evolution since its first application in the early 1990s. Especially
      the technical aspects of the genetic diagnosis itself, the single-cell genetic
      analysis, has constantly evolved to reach levels of accuracy and efficiency
      nearing those of genetic diagnosis on regular DNA samples. In this review, we
      will focus on the molecular biological techniques that are currently in use in
      the most advanced centers for PGD for monogenic disorders, including multiplex
      polymerase chain reaction (PCR) and post-PCR diagnostic methods, whole genome
      amplification (WGA) and multiple displacement amplification (MDA). As it becomes
      more and more clear that when it comes to ethically difficult indications, PGD
      goes further than prenatal diagnosis (PND), we will also briefly discuss ethical
      issues.

PMID- 19101954
TI  - Clinicopathological characteristics of intrahepatic cholangiocellular carcinoma
      presenting intrahepatic bile duct growth.
AB  - BACKGROUND: Intrahepatic cholangiocellular carcinoma (ICC) presenting intraductal
      growth (IG) has distinct clinicopathological features with a favorable prognosis.
      The mass-forming (MF) plus IG type of ICC has not been previously investigated.
      METHODS: One hundred forty-four patients with ICC underwent surgical resections
      and were classified according to the macroscopic type. The clinicopathological
      features of the IG type (n = 7) and MF plus IG type (n = 14) were retrospectively
      analyzed. The clinicopathological differences between the MF plus IG type and MF
      plus periductal infiltrating (PI) type (n = 37) were compared. RESULTS: All of
      the patients with the IG type had no sign of recurrence and survived. The 5-year
      overall survival rates was significantly better in the MF plus IG type than in
      the MF plus PI type (41.3% vs. 13.3%, P = 0.034). Significant differences were
      recognized between the MF plus IG type and MF plus PI type, in terms of vascular
      resection (P = 0.030), mucosal extension (P = 0.006), and postoperative
      recurrence (P = 0.004). CONCLUSIONS: The MF plus IG type had significantly better
      prognosis than the MF plus PI type. The IG type and MF plus IG type should be
      distinguished from other types even if hepatic hilar confluence is involved,
      because of the favorable outcome after surgery.

PMID- 19101955
TI  - Rectal cancer surgery and regional lymph nodes.
AB  - In patients with rectal cancer, the status of regional or mesorectal lymph nodes
      is central to both tumor staging and predicting local and distant recurrence. The
      importance of mesorectal lymph nodes in rectal cancer should inform treatment
      decisions around pre-operative diagnostic imaging, surgical techniques,
      pathologic assessment, and the use of radiation therapy.

PMID- 19101956
TI  - Scube1 is expressed during facial development in the mouse.
AB  - Scube1 encodes a secreted plasma membrane-associated protein characterized by a N
      terminal signal peptide sequence, multiple EGF domains, a N-linked glycosylated
      spacer region and a C-terminal CUB region. Here, we describe expression of the
      mouse Scube1 gene during early craniofacial development. Transcripts were
      identified in the nervous system, within the ventral neural tube, telencephalon
      and trigeminal ganglion. In addition, strong regionally restricted expression was
      found in the facial processes, including the medial and lateral nasal processes,
      maxilla and mandible, and caudal pharyngeal arches. During tooth development,
      Scube1 localized to the dental papilla of both incisor and molar teeth. Together,
      these data suggest a potential role for Scube1 during early craniofacial
      development.

PMID- 19101957
TI  - Temporal analysis of ectopic enamel production in incisors from sprouty mutant
      mice.
AB  - The mouse incisor has two unusual features: it grows continuously and it is
      covered by enamel exclusively on the labial side. The continuous growth is driven
      in part by epithelial stem cells in the cervical loop region that can both self
      renew and give rise to ameloblasts. We have previously reported that ectopic
      enamel is found on the lingual side of the incisor in mice with loss-of-function
      of sprouty (spry) genes. Spry2(+/-); Spry4(-/-) mice, in which three sprouty
      alleles have been inactivated, have ectopic enamel as a result of upregulation of
      epithelial-mesenchymal FGF signaling in the lingual part of the cervical loop.
      Interestingly, lingual enamel is also present in the early postnatal period in
      Spry4(-/-) mice, in which only two sprouty alleles have been inactivated, but
      ectopic enamel is not found in adults of this genotype. To explore the mechanisms
      underlying the disappearance of lingual enamel in Spry4(-/-) adults, we studied
      the fate of the lingual enamel in Spry4(-/-) mice by comparing the morphology and
      growth of their lower incisors with wild type and Spry2(+/-); Spry4(-/-) mice at
      several timepoints between the perinatal period and adulthood. Ameloblasts and
      enamel were detected on the lingual side in postnatal Spry2(+/-); Spry4(+/-)
      incisors. By contrast, new ectopic ameloblasts ceased to differentiate after
      postnatal day 3 in Spry4(-/-) incisors, which was followed by a progressive loss
      of lingual enamel. Both the posterior extent of lingual enamel and the time of
      its last deposition were variable early postnatally in Spry4(-/-) incisors, but
      in all Spry4(-/-) adult incisors the lingual enamel was ultimately lost through
      continuous growth and abrasion of the incisor.

PMID- 19101958
TI  - Macrocyclic cyclooctene-supported AlCl-salen catalysts for conjugated addition
      reactions: effect of linker and support structure on catalysis.
AB  - AlCl-salen (salen=N,N'-bis(salicylidene)ethylenediamine dianion) catalysts
      supported onto macrocyclic oligomeric cyclooctene through linkers of varying
      length and flexibility have been developed to demonstrate the importance of
      support architecture on catalyst activity. The role played by the support and the
      linkers in dictating catalyst activity was found to vary for reactions with
      contrasting mechanisms, such as the bimetallic cyanide and the monometallic
      indole addition reactions. While the flexible support significantly enhanced the
      cyanide addition reaction, most likely by improving salen-salen interactions in
      the transition state, it lowered the reaction rate for the monometallic indole
      reaction. For both reactions, significant increase in catalytic activity was
      observed for catalysts with the longest linkers. The effect of the flexible
      macrocyclic support on catalysis was further exemplified by the enhanced activity
      of the supported catalyst in comparison with its unsupported analogue for the
      conjugate addition of tetrazoles, which is known to be catalyzed by dimeric mu
      oxo-salen catalysts. Our studies with the cyclooctene supported AlCl-salen
      catalysts provides significant insights for rationally designing highly efficient
      AlCl-salen catalysts for a diverse set of reactions.

PMID- 19101959
TI  - (2,2-Diphenyl-[1,3]oxathiolan-5-ylmethyl)-(3-phenyl-propyl)-amine: a potent and
      selective 5-HT(1A) receptor agonist.
AB  - Starting from compound 1, a previously reported alpha(1D)-adrenoceptors
      antagonist, a new series of ligands acting at 5-HT(1A) serotonin receptor were
      identified through simple structure modifications. Among them (2,2-diphenyl
      [1,3]oxathiolan-5-yl-methyl)-(3-phenyl-propyl)amine (19) exhibits outstanding
      activity (pK(i)=8.72, pD(2)=7.67, E(max)=85) and selectivity (5
      HT(1A)/alpha(1D)>150), and represents an as yet unidentified 5-HT(1A) agonist
      scaffold.

PMID- 19101960
TI  - Cytotoxic rhodium(III) and iridium(III) polypyridyl complexes: structure-activity
      relationships, antileukemic activity, and apoptosis induction.
AB  - Meridional rhodium(III) polypyridyl complexes of the type mer-[RhX(3)(DMSO)(pp)]
      (X=Cl, pp=phen 1, dpq 2, dppz 3; X=Br, pp=phen 4) represent a promising class of
      potent cytostatic agents for the treatment of lymphoma and leukemia. Exposure of
      their DMSO solutions to light leads to slow isomerization to mixtures of the mer
      and the generally less active fac isomers. As a result, the IC(50) values of 1
      and 2 toward HT-29 cells increase from 0.19 and 0.069 microM on immediate use in
      the dark to 0.66 and 0.312 microM, respectively, after exposure of their DMSO
      stock solutions to light for 7 days. In striking contrast, the complexes mer
      [IrX(3)(DMSO)(phen)] (X=Cl 7, Br 8) are significantly less cytotoxic than their
      facial Ir(III) polypyridyl counterparts: IC(50)=20.3 microM for 7 and 4.6 microM
      for fac-[IrCl(3)(DMSO)(phen)] 5 toward MCF-7 cells. The IC(50) values for the
      complexes fac-[IrX(3)(L)(pp)] 9-13 decrease in the orders: a) Cl>Br for X and b)
      H(2)O>DMSO for L. Specific apoptotic cell death by DNA fragmentation was detected
      for leukemia (NALM-6) and lymphoma (BJAB) cells after incubation with 2, 3, and
      11 (X=Br, L=H(2)O, pp=phen) for 72 h. Loss of the mitochondrial membrane
      potential in lymphoma cells indicates that apoptosis is mediated via the
      intrinsic mitochondrial pathway. LDH release assays after 1 or 3 h demonstrate
      that necrotic damage is negligible.

PMID- 19101961
TI  - Complex long-range magnetic ordering behaviors in anisotropic cobalt(II)-azide
      multilayer systems.
AB  - The crystal structures and magnetic properties of two new Co(II) molecular
      magnets, [Co(N(3))(2)(btzb)] (1) and [Co(N(3))(2)(btze)(2)] (2), are described
      and discussed (btzb=1,4-bis(tetrazol-1-yl)butane and btze=1,4-bis(tetrazol-1
      yl)ethane). In the materials, (4,4) layers with mu-1,3-azide bridges are cross
      linked by the monolayered btzb bridging ligands or spaced by bilayered btze
      terminal ligands to give a 3D (1) or 2D (2) coordination network with
      significantly different interlayer separations (10.6 vs. 15.2 A). The observation
      that the layers in 1 and 2 are almost identical have not only allowed us to
      determine how the interlayer separation imposes its influences on their magnetic
      behavior, but also helps us understand the complex magnetic behavior of each
      structure. In the high-temperature range (>25 K), almost identical magnetic
      behaviors, typical of 2D antiferromagnetic systems, are observed for 1 and 2. At
      low temperature they exhibit unusual and different behaviors that combine spin
      canting (weak ferromagnetism), metamagnetism, and stepped hysteresis. It has been
      found that the interlayer separation has little influence on the ordering
      temperature (23 vs. 22 K), but imposes very-strong influence on the metamagnetic
      critical field (6500 vs. 450 Oe), the coercivity (7500 vs. 650 Oe), and the
      hysteresis-step size. It may also play an adjusting role in determining the
      canting angle. Taking into account the strong anisotropy of the systems and the
      interlayer dipolar interactions, we have reasonably interpreted the unusual
      metamagnetic and hysteresis behaviors and the differences between 1 and 2. In
      particularly, the stepped hysteresis loops have been explained by two weak
      ferromagnetic states.

PMID- 19101963
TI  - Revisiting the Aufbau reaction with acetylene: growth at aluminium producing a
      unique oligomer distribution.

PMID- 19101962
TI  - Pincer thioamide and pincer thioimide palladium complexes catalyze highly
      efficient Negishi coupling of primary and secondary alkyl zinc reagents at room
      temperature.
AB  - Pincer thioamide Pd(II) complex 2 was prepared, and its reaction with
      cyclohexylzinc chloride yielded novel pincer thioimide Pd(II) complex 3 besides
      Pd(0) species. The structures of complexes 2 and 3 were confirmed by X-ray
      analysis. Both complexes are efficient catalysts for Negishi couplings involving
      primary and secondary alkyl zinc reagents bearing beta-hydrogen atoms. At a
      concentration of 0.1-0.5 mol % both catalysts readily promoted reactions at room
      temperature or even at 0 degrees C. The operational simplicity of these
      processes, in conjunction with the easy accessibility of both catalysts and
      substrates, promises synthetic utility of this new methodology. An experiment on
      a scale of 19.35 g carried out at very low catalyst loading of 2 (turnover
      number: 6,100,000) highlighted the potential application of the catalytic system.
      Monoalkyl and dialkyl zinc reagents displayed different reactivities and
      selectivities in reactions with aryl iodides catalyzed by complexes 2 or 3, and
      isomerization in reactions involving acyclic secondary alkyl zinc derivatives was
      suppressed by using appropriate amounts of dialkyl zinc reagents. Based on
      preliminary kinetic profiles and reaction evidence, three possible pathways are
      proposed for the reactions involving acyclic secondary alkyl zinc reagents to
      rationalize the difference between mono-alkyl and dialkyl zinc derivatives.

PMID- 19101964
TI  - Belizeanolide, a cytotoxic macrolide from the dinoflagellate Prorocentrum
      belizeanum.

PMID- 19101965
TI  - Transition-metal-catalyzed propargylic substitution.

PMID- 19101966
TI  - Polymeric core-shell assemblies mediated by host-guest interactions: versatile
      nanocarriers for drug delivery.

PMID- 19101967
TI  - Tetraphosphabenzenes obtained via a triphosphacyclobutadiene intermediate.

PMID- 19101968
TI  - A dynamic kinetic asymmetric transformation in the alpha-hydroxylation of racemic
      malonates and its application to biologically active molecules.

PMID- 19101969
TI  - Hydrogen bonds as structural directive towards unusual polynuclear complexes:
      synthesis, structure, and magnetic properties of copper(II) and nickel(II)
      complexes with a 2-aminoglucose ligand.
AB  - The reaction of benzyl 2-amino-4,6-O-benzylidene-2-deoxy-alpha-D-glucopyranoside
      (HL) with the metal salts Cu(ClO(4))(2)6 H(2)O and Ni(NO(3))(2)6 H(2)O affords
      via self-assembly a tetranuclear mu(4)-hydroxido bridged copper(II) complex
      [(mu(4)-OH)Cu(4)(L)(4)(MeOH)(3)(H(2)O)](ClO(4))(3) (1) and a trinuclear
      alcoholate bridged nickel(II) complex [Ni(3)(L)(5)(HL)]NO(3) (2), respectively.
      Both complexes crystallize in the acentric space group P2(1). The X-ray crystal
      structure reveals the rare (mu(4)-OH)Cu(4)O(4) core for complex 1 which is mu(2)
      alcoholate bridged. The copper(II) ions possess a distorted square-pyramidal
      geometry with an [NO(4)] donor set. The core is stabilized by hydrogen bonding
      between the coordinating amino group of the glucose backbone and the benzylidene
      protected oxygen atom O4 of a neighboring {Cu(L)} fragment as hydrogen-bond
      acceptor. For complex 2 an [N(4)O(2)] donor set is observed at the nickel(II)
      ions with a distorted octahedral geometry. The trinuclear isosceles Ni(3) core is
      bridged by mu(3)-alcoholate O3 oxygen atoms of two glucose ligands. The two short
      edges are capped by mu(2)-alcoholate O3 oxygen atoms of the two ligands
      coordinated at the nickel(II) ion at the vertex of these two edges. Along the
      elongated edge of the triangle a strong hydrogen bond (244 pm) between the O3
      oxygen atoms of ligands coordinating at the two relevant nickel(II) ions is
      observed. The coordinating amino groups of the these two glucose ligands are
      involved in additional hydrogen bonds with O4 oxygen atoms of adjacent ligands
      further stabilizing the trinuclear core. The carbohydrate backbones in all cases
      adopt the stable (4)C(1) chair conformation and exhibit the rare chitosan-like
      trans-2,3-chelation. Temperature dependent magnetic measurements indicate an
      overall antiferromagnetic behavior for complex 1 with J(1)=-260 and J(2)=-205 cm(
      1) (g=2.122). Compound 2 is the first ferromagnetically coupled trinuclear
      nickel(II) complex with J(A)=16.4 and J(B)=11.0 cm(-1) (g(1,2)=2.183,
      g(3)=2.247). For the high-spin nickel(II) centers a zero-field splitting of
      D(1,2)=3.7 cm(-1) and D(3)=1.8 cm(-1) is observed. The S=3 ground state of
      complex 2 is consistent with magnetization measurements at low temperatures.

PMID- 19101970
TI  - Exploring the implications of vitamin B12 conjugation to insulin on insulin
      receptor binding.
AB  - We recently reported a vitamin B(12) (B(12)) based insulin conjugate that
      produced significantly decreased blood glucose levels in diabetic STZ-rat models.
      The results of this study posed a fundamental question, namely what implications
      does B(12) conjugation have on insulin's interaction with the insulin receptor
      (IR)? To explore this question we used a combination of molecular dynamics
      simulations and immunoelectron microscopy, and the results are described herein.
      This investigation demonstrates that chemical modification of insulin by linking
      relatively large pendant groups does not inherently interfere with IR
      recognition. Furthermore, given that we have previously demonstrated a
      significant drop in blood glucose concentration following the oral administration
      of the B(12)-insulin bioconjugate used in this work, it is reasonable to conclude
      that the IR recognition described herein is associated with maintenance of
      biological activity for insulin. This outcome offers significant research scope
      for chemical modification of insulin with the purpose of improving oral-uptake
      efficiency.

PMID- 19101971
TI  - Tritium-labeled N(1)-[3-(1H-imidazol-4-yl)propyl]-N(2)-propionylguanidine
      ([(3)H]UR-PI294), a high-affinity histamine H(3) and H(4) receptor radioligand.
AB  - This study reports the synthesis and pharmacological characterization of tritium
      labeled N(1)-[3-(1H-imidazol-4-yl)propyl]-N(2)-propionylguanidine ([(3)H]UR
      PI294), a novel and readily accessible radioligand for the human histamine H(3)
      receptor (hH(3)R) and H(4) receptor (hH(4)R). The radioligand displays high
      affinity for both histamine receptor subtypes (K(D) (hH(3)R)=1.1 nM, K(D)
      (hH(4)R)=5.1 nM) and is shown to be a valuable pharmacological tool for the
      determination of hH(3)R and hH(4)R affinities.

PMID- 19101972
TI  - Cation-pi interactions at the active site of factor Xa: dramatic enhancement upon
      stepwise N-alkylation of ammonium ions.

PMID- 19101973
TI  - Surprising simplicity in the single-molecule folding mechanics of proteins.

PMID- 19101974
TI  - Asymmetric Bronsted acid catalysis: catalytic enantioselective synthesis of
      highly biologically active dihydroquinazolinones.

PMID- 19101975
TI  - Efficient synthesis of chiral beta-arylisopropylamines by using catalytic
      asymmetric hydrogenation.

PMID- 19101976
TI  - Enantioselective synthesis of P-stereogenic phosphinates and phosphine oxides by
      molybdenum-catalyzed asymmetric ring-closing metathesis.

PMID- 19101977
TI  - Biosynthetic gene cluster of cetoniacytone A, an unusual aminocyclitol from the
      endosymbiotic Bacterium Actinomyces sp. Lu 9419.
AB  - A gene cluster responsible for the biosynthesis of the antitumor agent
      cetoniacytone A was identified in Actinomyces sp. strain Lu 9419, an
      endosymbiotic bacterium isolated from the intestines of the rose chafer beetle
      (Cetonia aurata). The nucleotide sequence analysis of the 46 kb DNA region
      revealed the presence of 31 complete ORFs, including genes predicted to encode a
      2-epi-5-epi-valiolone synthase (CetA), a glyoxalase/bleomycin resistance protein
      (CetB), an acyltransferase (CetD), an FAD-dependent dehydrogenase (CetF2), two
      oxidoreductases (CetF1 and CetG), two aminotransferases (CetH and CetM), and a
      pyranose oxidase (CetL). CetA has previously been demonstrated to catalyze the
      cyclization of sedoheptulose 7-phosphate to the cyclic intermediate, 2-epi-5-epi
      valiolone. In this report, the glyoxalase/bleomycin resistance protein homolog
      CetB was identified as a 2-epi-5-epi-valiolone epimerase (EVE), a new member of
      the vicinal oxygen chelate (VOC) superfamily. The 24 kDa recombinant histidine
      tagged CetB was found to form a homodimer; each monomer contains two
      betaalphabetabetabeta scaffolds that form a metal binding site with two histidine
      and two glutamic acid residues. A BLAST search using the newly isolated cet
      biosynthetic genes revealed an analogous suite of genes in the genome of Frankia
      alni ACN14a, suggesting that this plant symbiotic nitrogen-fixing bacterium is
      capable of producing a secondary metabolite related to the cetoniacytones.

PMID- 19101979
TI  - Riboswitches: ancient and promising genetic regulators.
AB  - BAIT AND SWITCH: Metabolite-sensing riboswitches make use of RNA structural
      modulation to regulate gene expression, as illustrated in the scheme, in response
      to subtle changes in metabolite concentrations. This review describes the current
      knowledge about naturally occurring riboswitches and their growing potential as
      antibacterial cellular targets and as molecular biosensors. Newly discovered
      metabolite-sensing riboswitches have revealed that cellular processes extensively
      make use of RNA structural modulation to regulate gene expression in response to
      subtle changes in metabolite concentrations. Riboswitches are involved at various
      regulation levels of gene expression, such as transcription attenuation,
      translation initiation, mRNA splicing and mRNA processing. Riboswitches are found
      in the three kingdoms of life, and in various cases, are involved in the
      regulation of essential genes, which makes their regulation an essential part of
      cell survival. Because riboswitches operate without the assistance of accessory
      proteins, they are believed to be remnants of an ancient time, when gene
      regulation was strictly based on RNA, from which are left numerous "living
      molecular fossils", as exemplified by ribozymes, and more spectacularly, by the
      ribosome. Due to their nature, riboswitches hold high expectations for the
      manipulation of gene expression and the detection of small metabolites, and also
      offer an unprecedented potential for the discovery of novel classes of
      antimicrobial agents.

PMID- 19101978
TI  - The molecular basis of inhibition of Golgi alpha-mannosidase II by mannostatin A.
AB  - Mannostatin A is a potent inhibitor of the mannose-trimming enzyme, Golgi alpha
      mannosidase II (GMII), which acts late in the N-glycan processing pathway.
      Inhibition of this enzyme provides a route to blocking the transformation
      associated changes in cancer cell surface oligosaccharide structures. Here, we
      report on the synthesis of new Mannostatin derivatives and analyze their binding
      in the active site of Drosophila GMII by X-ray crystallography. The results
      indicate that the interaction with the backbone carbonyl of Arg876 is crucial to
      the high potency of the inhibitor-an effect enhanced by the hydrophobic
      interaction between the thiomethyl group and an aromatic pocket vicinal to the
      cleavage site. The various structures indicate that differences in the hydration
      of protein-ligand complexes are also important determinants of plasticity as well
      as selectivity of inhibitor binding.

PMID- 19101981
TI  - Power frequency magnetic fields and risk of childhood leukaemia:
      misclassification of exposure from the use of the 'distance from power line'
      exposure surrogate.
AB  - A recent study examining the relationship between distance to nearby power lines
      and childhood cancer risk re-opened the debate about which exposure metrics are
      appropriate for power frequency magnetic field investigations. Using data from
      two large population-based UK and German studies we demonstrate that distance to
      power lines is a comparatively poor predictor of measured residential magnetic
      fields. Even at proximities of 50 m or less, the positive predictive value of
      having a household measurement over 0.2 microT was only 19.4%. Clearly using
      distance from power lines, without taking account of other variables such as
      load, results in a poor proxy of residential magnetic field exposure. We conclude
      that such high levels of exposure misclassification render the findings from
      studies that rely on distance alone uninterpretable.

PMID- 19101982
TI  - Unique phenotype of hepatocellular cancers with exon-3 mutations in beta-catenin
      gene.
AB  - Wnt/beta-catenin signaling plays an important role in liver development and
      regeneration. Its aberrant activation, however, is observed in a subset of
      primary hepatocellular cancers (HCCs). In the current study, we compare and
      contrast the tumor characteristics of HCC in the presence or absence of mutations
      in the beta-catenin gene (CTNNB1). Frozen HCCs (n = 32), including five
      fibrolamellar (FL) variants, and control livers (n = 3) from Health Sciences
      Tissue Bank and Department of Surgery at the University of Pittsburgh Medical
      Center, were examined for mutations in CTNNB1, protein levels of beta-catenin,
      tyrosine-654-phosphorylated-beta-catenin (Y654-beta-catenin), and glutamine
      synthetase (GS). Missense mutations in the exon-3 of CTNNB1were identified in
      9/32 HCCs. Total beta-catenin levels were higher than controls in most tumors;
      however, GS was exclusively increased in HCCs with mutations. Phenotypically,
      greater percentages of mutated HCCs showed macrovascular and microvascular
      invasion. Also, the tumor size was greater than double in mutated HCCs. High
      levels of total beta-catenin protein were observed in multinodular tumors
      independent of beta-catenin mutations. In addition, significant cases with
      mutations showed absence of cirrhosis. Finally, the highest levels of Y654-beta
      catenin were exclusively observed in fibrolamellar (FL)-HCC cases. CONCLUSION:
      Thus, HCCs that harbor missense mutations in exon-3 of CTNNB1 exhibit,
      histologically, a more aggressive phenotype. Also, CTNNB1 mutations might lead to
      HCC in the absence of cirrhosis. Finally, FL-HCC cases display a unique up
      regulation of tyrosine-phosphorylated-beta-catenin, suggesting robust receptor
      tyrosine kinase signaling in this tumor type.

PMID- 19101983
TI  - A cyp19a1b-gfp (aromatase B) transgenic zebrafish line that expresses GFP in
      radial glial cells.
AB  - Aromatase is an enzyme that catalyzes the synthesis of estrogen in gonads and
      brain. Teleost fish express aromatase (AroB) strongly in the brain facilitating
      its detailed examination. To understand the function of AroB in the brain, we
      generated transgenic zebrafish that expresses green fluorescent protein (GFP)
      driven by the brain aromatase cyp19a1b promoter. GFP was found in the radial
      glial cells of transgenic larvae and adult fish that overlap with AroB
      immunoreactivity in the correct temporal and spatial pattern. GFP was also
      coexpressed with radial cell marker BLBP, but was not in neurons. In addition,
      GFP expression in the radial glial cells was stimulated by estrogen, same as
      endogenous AroB expression. Thus, this transgenic line faithfully mimics the
      regulation of AroB expression in radial glial cells. It provides a powerful tool
      to further characterize progenitor radial cells in adult and developing fish and
      to evaluate estrogenic activities of xenoestrogens and phytoestrogens.

PMID- 19101984
TI  - Molecularly severe roX1 mutations contribute to dosage compensation in
      Drosophila.
AB  - Drosophila melanogaster males maintain a constant ratio of X-linked to autosomal
      gene products by increasing expression from their single X chromosome. This is
      achieved through the action of a complex composed of protein and roX RNA. This
      complex binds in the body of genes and increases expression through chromatin
      modification. The X-linked roX genes produce RNAs that are essential but
      redundant for recognition and modification of the male X chromosome. We report
      that some molecularly severe roX1 mutations with no detectable transcript
      accumulation contribute dramatically to male rescue by autosomal roX1 transgenes.
      We propose that this represents genetic complementation between a source of roX
      RNA (the autosomal transgene) and the severely mutated X-linked allele.

PMID- 19101985
TI  - Missense mutations and single nucleotide polymorphisms in ABCB11 impair bile salt
      export pump processing and function or disrupt pre-messenger RNA splicing.
AB  - The gene encoding the human bile salt export pump (BSEP), ABCB11, is mutated in
      several forms of intrahepatic cholestasis. Here we classified the majority (63)
      of known ABCB11 missense mutations and 21 single-nucleotide polymorphisms (SNPs)
      to determine whether they caused abnormal ABCB11 pre-messenger RNA splicing,
      abnormal processing of BSEP protein, or alterations in BSEP protein function.
      Using an in vitro minigene system to analyze splicing events, we found reduced
      wild-type splicing for 20 mutations/SNPs, with normal mRNA levels reduced to 5%
      or less in eight cases. The common ABCB11 missense mutation encoding D482G
      enhanced aberrant splicing, whereas the common SNP A1028A promoted exon skipping.
      Addition of exogenous splicing factors modulated several splicing defects. Of the
      mutants expressed in vitro in CHO-K1 cells, most appeared to be retained in the
      endoplasmic reticulum and degraded. A minority had BSEP levels similar to wild
      type. The SNP variant A444 had reduced levels of protein compared with V444.
      Treatment with glycerol and incubation at reduced temperature overcame processing
      defects for several mutants, including E297G. Taurocholate transport by two
      assessed mutants, N490D and A570T, was reduced compared with wild-type.
      CONCLUSION: This work is a comprehensive analysis of 80% of ABCB11 missense
      mutations and single-nucleotide polymorphisms at pre-mRNA splicing and protein
      processing/functional levels. We show that aberrant pre-mRNA splicing occurs in a
      considerable number of cases, leading to reduced levels of normal mRNA. Thus,
      primary defects at either the protein or the mRNA level (or both) contribute
      significantly to BSEP deficiency. These results will help to develop mutation
      specific therapies for children and adults suffering from intrahepatic
      cholestasis due to BSEP deficiency.

PMID- 19101987
TI  - Platelet-derived microparticles promote invasiveness of prostate cancer cells via
      upregulation of MMP-2 production.
AB  - Prostate cancer commonly affects men in the Western world. A major factor of the
      life-threatening course of this disease is the high rate of metastasis,
      predominantly to bones. Circulating tumor cells encounter platelets and may
      activate them, resulting in a production of microparticles (MPs). MPs are small
      platelet fragments expressing membrane receptors as well as cytoplasmic
      constituents. Here, we report that prostate cancer cells, Clone-1 (Cl-1),
      preincubated with platelet-derived MPs (PMPs), demonstrate increased invasion
      through a gelatin-coated (a denatured form of collagen) membrane of the Boyden
      chamber system. This effect was accompanied by an increased secretion of
      metalloproteinase-2 (MMP-2) as demonstrated by a gelatin zymography. Application
      of MMP-2/9 inhibitor reversed the PMP-induced tumor cell invasion. PMPs were
      shown to adhere to Cl-1 cells, but direct contact between them may not be
      mandatory for MMP secretion because PMP lysate induced MMP-2 production by Cl-1
      cells to the same extent as did intact PMPs. PMP-induced MMP-2 secretion was
      inhibited by neutralization of either PKC or total intracellular tyrosine
      phosphorylation, but was not affected by blocking major intraplatelet cytokines.
      Actinomycin D (a transcription inhibitor) did not modify this effect, whereas
      cycloheximide (an inhibitor of protein translation) abolished the MMP-2 release.
      MMP-2 secretion was accompanied by a rapid and transient increase in MMP-2 mRNA
      level after a 2-hr coincubation of prostate cancer cells with PMPs. Thus, PMPs
      promote tumor invasiveness, at least in part by stimulation of MMP-2 production.

PMID- 19101986
TI  - Radiation-induced HIF-1alpha cell survival pathway is inhibited by soy
      isoflavones in prostate cancer cells.
AB  - We previously showed that treatment of prostate cancer cells with soy isoflavones
      and radiation resulted in greater cell killing in vitro, and caused
      downregulation of NF-kappaB and APE1/Ref-1. APE1/Ref-1 functions as a redox
      activator of transcription factors, including NF-kappaB and HIF-1alpha. These
      molecules are upregulated by radiation and implicated in radioresistance of
      cancer cells. We extended our studies to investigate the role of HIF-1alpha
      survival pathway and its upstream Src and STAT3 molecules in isoflavones and
      radiation interaction. Radiation induced phosphorylation of Src and STAT3 leading
      to induction of HIF-1alpha. Genistein, daidzein or a mixture of soy isoflavones
      did not activate this pathway. These data were observed both in PC-3 (AR-) and C4
      2B (AR+) androgen-independent cell lines. Pretreatment with isoflavones inhibited
      Src/STAT3/HIF-1alpha activation by radiation and nuclear translocation of HIF
      1alpha. These findings correlated with decreased expression of APE1/Ref-1 and DNA
      binding activity of HIF-1alpha and NF-kappaB. In APE1/Ref-1 cDNA transfected
      cells, radiation caused a greater increase in HIF-1alpha and NF-kappaB activities
      but this effect was inhibited by pretreatment with soy prior to radiation.
      Transfection experiments indicate that APE1/Ref-1 inhibition by isoflavones
      impairs the radiation-induced transcription activity of NF-kappaB and HIF-1alpha.
      This mechanism could result in the inhibition of genes essential for tumor growth
      and angiogenesis, as demonstrated by inhibition of VEGF production and HUVECs
      tube formation. Our novel findings suggest that the increased responsiveness to
      radiation mediated by soy isoflavones could be due to pleiotropic effects of
      isoflavones blocking cell survival pathways induced by radiation including
      Src/STAT3/HIF-1alpha, APE1/Ref-1 and NF-kappaB.

PMID- 19101988
TI  - The gene expression signature of genomic instability in breast cancer is an
      independent predictor of clinical outcome.
AB  - Recently, expression profiling of breast carcinomas has revealed gene signatures
      that predict clinical outcome, and discerned prognostically relevant breast
      cancer subtypes. Measurement of the degree of genomic instability provides a very
      similar stratification of prognostic groups. We therefore hypothesized that these
      features are linked. We used gene expression profiling of 48 breast cancer
      specimens that profoundly differed in their degree of genomic instability and
      identified a set of 12 genes that defines the 2 groups. The biological and
      prognostic significance of this gene set was established through survival
      prediction in published datasets from patients with breast cancer. Of note, the
      gene expression signatures that define specific prognostic subtypes in other
      breast cancer datasets, such as luminal A and B, basal, normal-like, and ERBB2+,
      and prognostic signatures including MammaPrint and Oncotype DX, predicted genomic
      instability in our samples. This remarkable congruence suggests a biological
      interdependence of poor-prognosis gene signatures, breast cancer subtypes,
      genomic instability, and clinical outcome.

PMID- 19101989
TI  - Effects of sunitinib on tumor hemodynamics and delivery of chemotherapy.
AB  - Current clinical protocols favor a combination of antiangiogenic/antivascular
      compounds with classical chemotherapy. However, it remains unclear to what extent
      an antiangiogenic/antivascular therapy influences the delivery of chemotherapy.
      Therefore, the aim of the present study was to characterize the effects of the
      antiangiogenic tyrosine kinase inhibitor sunitinib on tumor microhemodynamics and
      delivery of chemotherapy. SF126 tumor cells were implanted subcutaneously into
      nude mice and were analyzed repeatedly by intravital microscopy. Treatment with
      sunitinib was initiated 7 days after implantation. To assess the effects of
      sunitinib on tumor vasculature and hemodynamics, we analyzed total and functional
      vessel densities, microvascular diameter, and microvascular blood flow rate. To
      study the delivery of chemotherapy, autofluorescent doxorubicin was systemically
      administered and its vascular delivery to the tumor tissue was quantified.
      Histological analysis included endothelial cell proliferation, pericyte coverage
      of tumor vessels, and tumor cell proliferation. Sunitinib significantly
      suppressed tumor growth by both antivascular and antiangiogenic effects. However,
      a number of tumor vessels escaped antiangiogenic therapy. Interestingly, in these
      surviving blood vessels sunitinib treatment resulted in an increased
      microvascular blood flow rate resulting in an improved delivery of chemotherapy
      via these blood vessels. Besides its potent antiangiogenic and antivascular
      efficacy, sunitinib treatment results in improved microhemodynamics and blood
      flow in tumor blood vessels that escape therapy leading to an improved vascular
      delivery of chemotherapy. These results provide the basis for a potential
      chemosensitizing effect of sunitinib.

PMID- 19101990
TI  - Oviduct-specific glycoprotein is a molecular marker for invasion in endometrial
      tumorigenesis identified using a relevant mouse model.
AB  - The light microscopic distinction between complex atypical hyperplasia (CAH) and
      invasive endometrioid carcinoma (UEC) on endometrial sampling is problematic and
      often has significant clinical implications. Using mouse models of endometrial
      tumorigenesis based on two of the most common molecular alterations found in
      primary human UEC we sought to characterize the transition from CAH to carcinoma
      to identify clinically useful biomarkers. We used the previously described
      Pten(+/-); Mlh1(-/-) mouse model. DNA was isolated from microdissected lesions
      (CAH and carcinoma) and analyzed for LOH and mutations of Pten and additional
      candidate genes. To identify novel candidate genes associated with invasion,
      global gene expression profiles were compared from uteri with extensive CAH and
      carcinoma. The majority of CAHs and carcinomas, arising in this model showed
      biallelic inactivation of Pten mediated through LOH or intragenic mutation of the
      wild-type allele suggesting that complete loss of Pten is insufficient for the
      development of carcinoma. The global gene expression studies detected increased
      expression of oviduct-specific glycoprotein (OGP) in carcinoma as compared with
      CAHs. This finding was validated using immunohistochemical staining in a
      collection of primary human UECs and CAHs. Our studies identify a molecular
      marker for invasive endometrial cancer that may have clinical significance, and
      highlight the usefulness of this mouse model in not only understanding the
      genetic underpinnings of endometrial carcinoma, but as a tool to develop
      clinically relevant biomarkers.

PMID- 19101991
TI  - Radiation-induced cathepsin S is involved in radioresistance.
AB  - Previous studies have suggested that the production of cathepsin S (CatS), a
      cysteine protease, was specifically induced in radiation-induced rat mammary
      tumors. In this study, we further investigate the mechanism by which CatS is
      induced by radiation and its function. Radiation induced production of CatS at
      both the mRNA and protein level, and increased its protease activity. In
      addition, these radiation induced changes occurred in a dose and time-dependent
      fashion. Agents such as bleomycin, As(2)O(3) and H(2)O(2), which produce reactive
      oxygen species (ROS), also induced CatS expression; however, other agents that
      damage DNA such as taxol and cisplatin did not. Additionally, treatment of the
      cells with the ROS scavengers, N-acetylcysteine and catalase, inhibited the
      radiation induced CatS expression. Furthermore, radiation-induced ROS was also
      involved in IFN-gamma production, which was responsible for radiation-mediated
      CatS expression. Moreover, electrophoretic mobility shift assay (EMSA) data
      obtained using an IFN-stimulated response element (ISRE) oligonucleotide revealed
      that IFN regulatory factor-1 (IRF1) was the critical transcriptional mediator of
      IFN-gamma-dependent CatS production after radiation. Finally, CatS overespression
      was found to induce radioresistance; however, knockdown of CatS resulted in the
      suppression of radioresistance. Taken together, the results of this study
      indicate that radiation induced CatS expression via ROS-IFN-gamma pathways, and
      that this increased expression may be involved in radioresistance.

PMID- 19101992
TI  - Over-expression of phosphatase of regenerating liver-3 correlates with tumor
      progression and poor prognosis in nasopharyngeal carcinoma.
AB  - This study aimed at clarifying the expression of phosphatase of regenerating
      liver-3 (PRL-3), one member of protein tyrosine phosphatase (PTP) superfamily, in
      nasopharyngeal carcinoma (NPC) and its correlation with clinicopathologic
      features, including the survival of patients with NPC. Real-time PCR and Western
      blot showed that the expression level of PRL-3 was markedly higher in NPC cell
      lines than that in the normal nasopharyngeal epithelial cell at both mRNA and
      protein levels. Immunohistochemical analysis revealed overexpression of PRL-3 in
      97 of 174 (55.7%) paraffin-embedded archival NPC biopsies. Statistical analysis
      showed that PRL-3 expression was positively correlated with N classification (p =
      0.033), distant metastasis (M classification, p = 0.048) and clinical stage (p =
      0.005) of patients. Patients with higher PRL-3 expression had shorter overall
      survival time, whereas patients with lower level of PRL-3 had better survival.
      Multivariate analysis suggested that PRL-3 expression might be an independent
      prognostic indicator for the survival of patients with NPC. Disruption of
      endogenous PRL-3 protein through a siRNA knockdown technique was shown to
      suppress the invasion ability and migration potency of 5-8F and HONE1 cells,
      substantially. Interestingly, we also found that no significant effect on the
      proliferation of 5-8F and HONE1 cells was observed after PRL-3 was down
      regulated. Our results suggest that PRL-3 protein is a valuable marker for
      progression of NPC patients. High PRL-3 expression is associated with poor
      overall survival in patients with NPC.

PMID- 19101993
TI  - Early detection of adrenocortical carcinoma in a child with Li-Fraumeni syndrome.
AB  - We report an early detection of cancer in a child with Li-Fraumeni syndrome. The
      proband was a 3-year-old male with a primitive mesenchymal tumor. Genetic
      analysis showed a germline TP53 mutation in codon 220 exon 6, which changed TAT -
      > TGT and resulted in a tyrosine-to-cysteine amino acid substitution (Tyr220Cys).
      The younger sister at risk was followed, and an asymptomatic adrenal cortical
      carcinoma was detected 3 years later. The report highlights the importance of
      genetic counseling and provides an example of early detection of cancers in
      childhood LFS carriers.

PMID- 19101994
TI  - Potential chemotherapy side effects: what do oncologists tell parents?
AB  - BACKGROUND: In order to determine the number of short-term side effects and late
      effects discussed during an informed consent conference (ICC) after the diagnosis
      of acute leukemia, we observed the occurrence(s) and the ratio between short-term
      side effects versus late effects during an ICC. PROCEDURE: ICC(s) of childhood
      leukemia trials were audio-taped at six different study sites. The side effects
      mentioned during each of these ICC(s) were coded and analyzed. RESULTS: One
      hundred forty cases were reviewed, from which we coded a total of 3,173 acute
      side effects and 242 late effects. The mean total side effects mentioned during
      each ICC was 24 (range 5-47). The number of late effects coded were significantly
      less than acute side effects. We also found that the duration of ICC(s) was
      positively correlated with the number of side effects mentioned. In addition, the
      frequency of total side effects mentioned was independent of patient or parent
      demographic factors. CONCLUSIONS: Our results show that acute side effects are
      often mentioned but the discussion of late effects is much less frequent in the
      initial ICC(s). Careful consideration regarding the ratio of acute and late
      effects that are communicated to parents in the context of the ICC may facilitate
      parental understanding of clinically relevant side effects.

PMID- 19101995
TI  - Bevacizumab treatment in multifocal lymphangioendotheliomatosis with
      thrombocytopenia.
AB  - Multifocal lymphangioendotheliomatosis with thrombocytopenia (MLT) is a rare
      disorder characterized by a proliferation of cutaneous and gastrointestinal (GI)
      lesions that have characteristics of both lymphatic and vascular lesions.
      Thrombocytopenia is associated with this syndrome and is thought to represent
      platelet destruction within the lesions. The natural history is one of multiple,
      life-threatening episodes of GI bleeding. We report the successful use of
      bevacizumab in this disease, an antibody to the vascular endothelial growth
      factor.

PMID- 19101996
TI  - Reversible posterior leukoencephalopathy syndrome in a child treated with
      bevacizumab.
AB  - Bevacizumab is a monoclonal antibody targeting vascular endothelial growth factor
      (VEGF). Hypertension is a well-recognized, common side effect of VEGF blocking
      agents. The reversible posterior leukoencephalopathy syndrome (RPLS) has been
      described as a rare but serious consequence of bevacizumab administration. We
      present a case of a 6-year-old child with refractory hepatoblastoma who developed
      hypertensive crisis, seizures and MRI changes consistent with RPLS while
      receiving bevacizumab with gemcitabine and oxaliplatin. Findings completely
      resolved without neurologic sequelae with stringent blood-pressure control.
      Better understanding of risk for RPLS, prompt recognition and aggressive
      management will be required as bevacizumab gains wider use in pediatrics.

PMID- 19101997
TI  - Allogeneic stem cell transplantation for Glanzmann thrombasthenia.
AB  - Glanzmann thrombasthenia (GT) is a rare autosomal recessive bleeding disorder
      characterized by normal platelet count, but lack of platelet aggregation. The
      molecular basis is linked to quantitative and/or qualitative abnormalities of the
      membrane glycoprotein IIb/IIIa complexes. Usually it is associated with mild
      bleeding but may lead to severe and potentially fatal hemorrhages. Allogeneic
      hematopoietic stem cell transplantation (HSCT) is the only curative treatment.
      However, because of the risks associated with HSCT, it is generally not
      recommended unless there are life threatening hemorrhages, or the patient has
      developed refractoriness to platelet transfusion due to antibody formation.
      Herein, we report an 11-year-old female from United Arab Emirates (UAE) with
      severe GT and anti platelet alloimmunization successfully treated with HSCT from
      her HLA-identical sibling.

PMID- 19101998
TI  - Computed tomography reformation in evaluation of fracture healing with metallic
      fixation: correlation with clinical outcome.
AB  - BACKGROUND: The amount of callous needed for fracture stability is typically
      estimated by a combination of radiographic and physical examinations. Computed
      tomography (CT) with sagittal and coronal reformations was performed to determine
      the amount of callous needed for fracture stability based on a quartile analysis
      of bony bridging of the circumference of the fracture site. METHODS: All patients
      who received CT with sagittal and coronal reformations of a fractured tubular
      bone for the purpose of analyzing bony bridging over a 22-month period were
      retrospectively reviewed. The final analysis included 34 patients and a total of
      47 examinations. Fractures were placed into one of four groups depending on the
      amount of cortical bridging of the circumference of the bone: group I, 0-24%,
      group II, 25-49%, group III, 50-74%, group IV, 75-100%. Clinical outcome was
      determined on the basis of fracture stability, with mean follow-up of
      approximately 62 weeks. RESULTS: A statistically significant increase in clinical
      failure was found in patients with <25% bridging. A cut-point analysis revealed
      that 37.5% (6 of 16) of failures occurred among patients with <25% bony bridging,
      and only 9.7% (3 of 31) of failures occurred among patients with >25% bridging,
      corresponding to a Fisher's exact test p value of 0.045. CONCLUSIONS: Patients
      with less than 25% bridging of the circumference of a tubular bone should be
      considered high risk for failure, indicating the need for continued protection of
      the site.

PMID- 19101999
TI  - Recurrent dorsal compartment syndrome of the upper arm after blunt trauma.

PMID- 19102000
TI  - [A family with multiple cases of lumbar-sacral disk herniations].

PMID- 19102001
TI  - Redefining case management.

PMID- 19102002
TI  - Checking up on retail-based health clinics: is the boom ending?
AB  - Retail store-based health clinics, which provide basic preventive services and
      diagnose and treat simple health ailments, have proliferated rapidly in recent
      years. Younger families and people that have difficulty accessing health care
      services--including the uninsured and minorities--are among the groups most
      likely to use these clinics. Still, in 2007, only 1.2 percent of U.S. families
      reported they had visited a retail clinic during the past 12 months, and only 2.3
      percent of families reported ever having visited one, according to the Health
      Tracking Household Survey conducted by the Center for Studying Health System
      Change. The boom in retail clinics, moreover, appears to be slowing. Continued
      fall-off in the growth of retail clinics would likely disproportionately affect
      underserved Americans who lack affordable alternatives for primary care.

PMID- 19102003
TI  - [Hope in the fight against malaria].

PMID- 19102004
TI  - Discussion on California Proposition 2 continues.

PMID- 19102006
TI  - [Equal access for all].

PMID- 19102005
TI  - [Retirement of creatinine kinase myocardial band is not recommended].

PMID- 19102007
TI  - Amplified in breast cancer 1 expression in breast cancer.
AB  - AIMS: The amplified in breast cancer 1 (AIB1), steroid receptor co-activator
      family member, acts as an oestrogen receptor (ER) co-activator. Acting with HER
      2, it is thought to play a role in endocrine resistance by facilitating ER-growth
      factor crosstalk. The aim was to analyse AIB1 expression by immunohistochemistry
      and study its correlations with other prognostic variables in breast cancer and
      its effect on survival. METHODS: A tissue microarray comprising tumours from 438
      patients with 15.4 years' median follow-up was used. Interpretable AIB1
      expression obtained in 395 patients was analysed along with other prognostic
      factors in breast cancer. RESULTS: AIB1 expression scores ranged from 0 to 30;
      positive AIB1 expression (score > 14) was seen in 146/395 breast cancers; it
      correlated negatively with ER (P = 0.003) and progesterone receptor (PR) (P =
      0.007), and positively with HER-2 (P = 0.005) and tumour grade (P = 0.014). It
      did not correlate with nodal status (P = 0.437). Among ER+ patients, AIB1
      expression showed a trend towards loss of PR expression (29% versus 20%; P =
      0.14). AIB1 did not predict survival on univariate or multivariate analysis.
      CONCLUSIONS: AIB1 expression correlates with HER-2 expression in breast cancer
      and shows a trend of association with loss of PR expression in ER+ tumours. Our
      study supports the postulated role of AIB1 in ER-growth factor interactions.

PMID- 19102008
TI  - Intratumoural heterogeneity of intestinal expression reflects environmental
      induction and progression-related loss of induction in undifferentiated-type
      gastric carcinomas.
AB  - AIMS: Gene expression in tumours is regulated by environmental as well as
      genetic/epigenetic factors. This study assessed the environmental factors in
      intestinal expression of gastric cancers. METHODS AND RESULTS: We
      immunohistochemically examined intratumoural heterogeneity in the expression of
      Cdx2, MUC2, MUC5AC and MUC6 in 39 intramucosal and 49 extramucosally invasive
      undifferentiated-type gastric carcinomas (UGCs), consisting of signet ring cell
      carcinomas showing a layered structure (LS) in the mucosa and dedifferentiated
      tubular adenocarcinomas without LS and with minor tubular components (TC). The LS
      retains mucosal vertical polarity with superficial MUC5AC expression. Loss of
      this polarity was independent of intestinal expression and associated with
      extramucosal invasion. In LS(+) UGCs, intestinal expression was enhanced as the
      size of mucosal spread increased and was significantly reduced with deeper
      extramucosal invasion, whereas, in LS(-)/TC(+) UGCs, intestinal expression was
      frequent and predominant in the mucosa and was insignificantly reduced with
      deeper extramucosal invasion. CONCLUSIONS: In LS(+) UGCs, intestinal expression
      showed dynamic alteration probably by environmental induction and progression
      related loss of induction, whereas it was relatively stable in LS(-)/TC(+) UGCs.
      Thus, intestinal expression in UGCs is not useful as a marker of tumour
      progression because it is also affected by environmental factors and genetic
      lineage.

PMID- 19102009
TI  - EGFR, HER-2 and COX-2 levels in colorectal cancer.
AB  - AIMS: Receptor tyrosine kinases epidermal growth factor receptor (EGFR) and HER-2
      and cyclooxygenase-2 (COX-2) are promising molecular targets for cancer therapy
      and/or prevention. The aim was to evaluate EGFR, HER-2 and COX-2 mRNA and protein
      expression in colorectal cancer patients. METHODS AND RESULTS: EGFR, HER-2 and
      COX-2 protein levels were evaluated by immunohistochemistry in malignant tissue,
      dysplastic tissue and normal mucosa samples from 124 cases with primary
      colorectal carcinoma. Moreover, the corresponding mRNA levels were assessed by
      quantitative reverse transcriptase-polymerase chain reaction in 46 colorectal
      carcinomas. There was strong correlation between mRNA and protein expression for
      EGFR (P < 0.001), HER-2 (P < 0.004) and COX-2 (P < 0.007). EGFR levels did not
      correlate with stage of the disease or tumour differentiation. HER-2 and COX-2
      levels increased in advanced stages and in differentiated carcinomas.
      Furthermore, a correlation between HER-2 and COX-2 expression was revealed in
      neoplastic tissue. CONCLUSIONS: EGFR as well as HER-2 and COX-2 overexpression
      represent important alterations that are related to the molecular pathways
      underpinning colorectal carcinogenesis. Further investigation is required to
      evaluate the impact of these markers on the management of patients with
      colorectal cancer.

PMID- 19102010
TI  - Smoking-related changes in the background lung of specimens resected for lung
      cancer: a semiquantitative study with correlation to postoperative course.
AB  - AIMS: To assess the pathological findings in lobectomy specimens, to correlate
      them with smoking history and postoperative course and to compare the findings
      with those in smoking-related interstitial lung disease. METHODS AND RESULTS:
      Patients who had undergone lobectomy for lung cancer were reviewed. Subjects
      included 230 non-smokers and 587 smokers, of whom 572 had a known smoking index
      (SI). They were classified into mild, moderate and heavy smokers. Centrilobular
      emphysema (CLE), respiratory bronchiolitis, airspace enlargement with fibrosis
      (AEF), the presence of foci resembling usual interstitial pneumonia pattern
      (UIP/P) and the rate of postoperative respiratory failure were assessed. The
      incidence of AEF was 6.5% in mild smokers, and 17.7% in moderate smokers (P <
      0.01) with lower lobe predominance. There were significant correlations (P <
      0.01) between AEF and CLE and AEF and UIP/P. The rate of respiratory failure
      after lobectomy was 6%, and 10% in patients having UIP/P with or without AEF, but
      was not seen in patients with AEF alone (P < 0.01). CONCLUSIONS: AEF is an
      important smoking-related change in the lung that appears to correlate with the
      smoking history, and its distinction from UIP/P may be important.

PMID- 19102011
TI  - Cetuximab in head and neck cancer.

PMID- 19102012
TI  - Military medical ethics.

PMID- 19102013
TI  - [Assessment health damage from use of tobacco aromatizers].
AB  - Some concentrated natural tobacco aromatizers (FL-Marwal, FL-Achshe, FL-Vlakot)
      and casings (CC-Catjas, CC-Wenget, CC-Krawat) from British American Tobacco
      Germany GmbH (Germany) imported into the Republic of Uzbekistan to be used in the
      manufacture of cigarettes were tested. The author's toxicological studies have
      revealed that the test agents may be recommended for use in the manufacture of
      cigarettes as safe tobacco aromatizers and casings. The normal life span
      reduction caused by the test natural concentrated tobacco aromatizers and casings
      in the hygienic range will be expected to be 3-6 days a year.

PMID- 19102014
TI  - [Hygienic evaluation of the influence of environmental factors on adolescents'
      health in a gas-and-oil producing region].
AB  - Environmental factors in a gas-and-oil producing region were hygienically
      evaluated for their influence on the health of adolescents living in the towns of
      the Khanty-Mansi Autonomous District (KMAD) - Yugry. The air was found to be
      polluted by incomplete oil and gas combustion products from flares, by emission
      from emergency conditions at gas-and-oil-producing enterprises. The major ambient
      air pollutants were formaldehyde, nitrogen dioxide, and suspended solids. The
      hazard indices upon combined exposure to chemicals were 9.81, 7.65, 4.79, and
      4.01 in Nizhnevartovsk, Surgut, Nefteyugansk, Khanty-Mansiysk, respectively. The
      population's potential health risk associated with a water factor in all the four
      towns was due to the presence of manganese and silicon. Hazardous substances
      available in the ambient air and water, as well as natural and climatic living
      conditions were ascertained to influence the health of adolescents. The results
      of the study served as a basis for substantiation of measures to reduce pollution
      of ambient air and drinking water supply objects in the KMAD-Yugry and a package
      of measures to improve the health of adolescents.

PMID- 19102015
TI  - [The content of ben(z)pyrene in ondulin proposed as an asbestos cement roofing
      slate substitute].

PMID- 19102016
TI  - [Deleterious factors of metal manufacture and the development of dental
      diseases].
AB  - Clinical evidence has been provided for the negative influence of the deleterious
      factors of metal manufacture and the extreme climatic and geographic conditions
      of the Far North.

PMID- 19102017
TI  - [Effect of toxins of cyanobacteria of the Microcystis genus from the Shershnevo
      Reservoir on DNA, cell cycle, and apoptosis of bone marrow cells in CBA mice].
AB  - The effect of toxins of a Cyanobacterium sample of the Shershnevo Reservoir on
      DNA, which was presented by cyanobacteria of the Microcystis genera, on the bone
      marrow of male CBA mice (whose age was 3 months and weight 24 g) was evaluated.
      With intraperitoneal administration, LD50 and LD16 of this sample for male CBA
      mice were 48.4 and 42.1 mg/kg, respectively. Administration of Microcystis
      cyanobacterial sample from the Shershnevo Reservoir in doses of 1/10 of LD16 and
      1/2 of LD16, and LD16 was found to cause a dose-dependent reduction in the number
      of bone marrow nucleated cells, a dose-dependent increase in the rate of cell
      apoptotic death, a reduction in the duration of a cell cycle (within the first 12
      hours), which gave way to an increase in the duration of the cycle 24 hours after
      administration, a dose-dependent increase in the frequency of micronuclei in the
      murine bone marrow eryphrocytes, and a dose-dependent decrease in the
      polychromatophil/normochromatophil ratio in the murine bone marrow.

PMID- 19102018
TI  - [Toxicological evaluation of chronic exposure to dinil].
AB  - Experiments on rats were carried out to study the effect of dinil on the animals
      on chronic intake of the agent in the quantities exceeding the maximum
      permissible concentrations by many times. Despite few biochemical changes, there
      was a certain tension of adaptive processes, which appeared as a change mainly in
      the integral characteristics of the plasma amino acid pool. The observed changes
      in the levels of neurotransmitters and neuroactive amino acids in the striatum,
      midbrain, and hypothalamus are characterized by specific characteristics and may
      underlie the negative effect of dinil on central nervous system functions. Long
      term administration of the agent to the animals did not induce pronounced
      morphological and biochemical disturbances in the tissues of the liver, heart,
      and kidneys. Changes in the concentrations of serotonin and neuroactive amine
      acids in the brain regions might have the greatest consequences to the body.
      Since the detectable changes in a number of metabolites are likely to be
      functional in the given period (monthly dinil use), an attempt to correct
      developing disorders with metabolic therapy agents may be recommended.

PMID- 19102019
TI  - [Organization of monitoring of electromagnetic radiation in the urban
      environment].
AB  - The authors describe new current approaches to monitoring the environment,
      including the sources of electromagnetic radiation and noise. Electronic maps of
      the area under study are shown to be made, by constructing the isolines or
      distributing the actual levels of controlled factors. These current approaches to
      electromagnetic and acoustic monitoring make it possible to automate a process of
      measurements, to analyze the established situation, and to simplify the risk
      controlling methodology.

PMID- 19102020
TI  - [Practice management economic index figures for the medical practice].

PMID- 19102021
TI  - [Retaining your patients and winning new patients with the practice home page].

PMID- 19102022
TI  - [Threatened revolution from above].

PMID- 19102023
TI  - [Goal performance principle in the legal decision of the federal court--most
      recent decision of 5 June 2008 once again confirms its application].

PMID- 19102024
TI  - [22nd Surgery Day, 17 to 18 October 2008, Langenbeck Virchow House, Berlin].

PMID- 19102025
TI  - Health plan pharmacy director: considerations for treatment and management of RSV
      disease.
AB  - RSV immunoprophylaxis presents a challenge for MCOs. Despite its demonstrated
      ability to protect high-risk infants against serious RSV infection and to reduce
      morbidity, immunoprophylaxis with palivizumab incurs high costs that MCOs must
      grapple with every year. If MCOs, physicians, and professional organizations can
      agree on common guidelines for RSV management, then MCOs will be able to provide
      affordable treatment for those children at high risk.

PMID- 19102026
TI  - The utility of the "notch" sign.

PMID- 19102027
TI  - [At the end of the rainbow....].

PMID- 19102028
TI  - [Attend to liquidity!].

PMID- 19102029
TI  - [Breaking the dams].

PMID- 19102030
TI  - [DRG practice: exchange of prosthesis components of the hip joint].

PMID- 19102031
TI  - [Changes in contract physician/accident insurance carrier (1 April 2008
      edition)].

PMID- 19102032
TI  - ["New brooms sweep well!?"--2].

PMID- 19102033
TI  - Coat protein gene sequence analysis of potato virus X and potato virus Y:
      conserved regions to design gene silencing cassette.
AB  - Potato virus X(PVX) and Potato virus Y(PVY) are two of the three most prevalent
      viruses that cause significant yield declines in potato. Twenty-seven PVX and
      thirty-seven PVY accessions were analyzed for nucleotide sequence variation of
      the coat protein gene. The average and variance of genetic distance for PVX were
      estimated at 0.118 and 0.004 and 0.118 and 0.005 for PVY using the neighbour
      joining method. Results of phylogenetic trees and their certification via
      stepwise discriminant analysis led us to classify of PVX sequences in four groups
      and PVY sequences in three groups. One purpose of this project was to determine
      suitable conserved regions to make of gene silencing constructs. Length of
      identified conserved regions were enough to silence of the virus coat protein
      genes on infected plants, many of which were located consequently with short gap
      spacers. In this term, some of groups were divided into subgroups to obtain
      conserved regions under minimum length of25 nt, enough length to design specific
      diagnostic-primers.

PMID- 19102034
TI  - Resynchronization/defibrillation for ambulatory heart failure  trial: rationale
      and trial design.
AB  - PURPOSE OF REVIEW: This paper reviews the effect of cardiac resynchronization
      therapy (CRT) on patients with heart failure symptoms, in particular, in patients
      with mild symptoms of heart failure. It provides the rationale and design of a
      randomized controlled trial to determine if CRT, when added to implantable
      cardioverter defibrillator, will be beneficial in patients with left ventricular
      dysfunction, ventricular conduction delay and mild heart failure symptoms. RECENT
      FINDINGS: CRT has been demonstrated to improve functional capacity, quality of
      life, and reduce heart failure hospitalization in patients with advanced
      symptomatic heart failure, and evidence of a ventricular conduction abnormality
      on ECG. In patients with milder heart failure symptoms, three randomized
      controlled trials and observational studies failed to convincingly show
      improvement of functional status, but demonstrated improved ventricular reverse
      remodelling with more advanced heart failure patients. SUMMARY: Two large
      randomized clinical trials are currently ongoing (RAFT and MADIT-CRT). The
      results of these trials will determine the efficacy of CRT in patients with
      systolic heart failure, ventricular conduction abnormality and milder symptoms.

PMID- 19102035
TI  - Critical appraisal of methods to assess mechanical dyssynchrony.
AB  - PURPOSE OF REVIEW: To analyze the strength and weakness of various imaging tools
      for systolic dyssynchrony assessment in the cardiac resynchronization therapy
      (CRT) era. Also, controversies and problematic issues of the recent predictors of
      response to cardiac resynchronization therapy study were addressed. RECENT
      FINDINGS: Despite published data from experienced centers that echocardiographic
      parameters of systolic dyssynchrony assessment with defined cutoff values were
      able to predict favorable response to CRT (septal-to-posterior wall delay by M
      mode of 130 ms, tissue Doppler imaging of septal-to-lateral wall delay of 65 ms
      and Ts-SD of 33 ms, and speckle tracking delay in septal-to-posterior wall radial
      strain of 130 ms), the recent predictors of response to cardiac resynchronization
      therapy (PROSPECT) study did not concur with the observations. However, the
      latter study was flawed in multiple areas including site selection bias,
      dyssynchrony training, and selection of echocardiography equipment, echo core
      laboratory experience and echocardiographic image quality surveillance. These
      factors acting in concert contributed to the high variability of dyssynchrony
      parameters, high echocardiographic data missing rate, and inconsistent
      measurement, which will not determine if dyssynchrony predicts a higher response
      rate than QRS duration alone. SUMMARY: There is a learning curve for dyssynchrony
      assessment. Without proper dyssynchrony training and experience accumulation in a
      large number of implanting centers worldwide, a rush into multicenter trials that
      only focus on experienced device implantation will not be possible to replicate
      the role of dyssynchrony assessment.

PMID- 19102036
TI  - Atrial fibrillation and congestive heart failure.
AB  - PURPOSE OF REVIEW: The present review will examine the prognostic importance of
      atrial fibrillation and heart failure, explore the different therapeutic options
      for treating atrial fibrillation and present the results of the Atrial
      Fibrillation and Congestive Heart Failure (AF-CHF) trial. RECENT FINDINGS: The
      Atrial Fibrillation and Congestive Heart Failure trial was a randomized trial
      involving patients with both atrial fibrillation and heart failure. The trial was
      designed to compare the maintenance of sinus rhythm with the control of
      ventricular rate in patients with left ventricular dysfunction, heart failure and
      a history of atrial fibrillation. There was no significant difference in the rate
      of death from cardiovascular causes in the rhythm-control group as compared with
      the rate-control strategy. In addition, there was no significant difference in
      any of the secondary outcomes including death from any cause, worsening heart
      failure or stroke. The rate-control strategy eliminated the need for repeated
      cardioversion and reduced rates of hospitalization. SUMMARY: The results of the
      Atrial Fibrillation and Congestive Heart Failure trial indicate that a routine
      strategy of rhythm control does not reduce rate of death and suggest that rate
      control should be considered a primary approach for patients with atrial
      fibrillation and heart failure.

PMID- 19102037
TI  - How to identify and treat patient with pulmonary vein stenosis  post atrial
      fibrillation ablation.
AB  - PURPOSE OF REVIEW: The diagnosis of pulmonary vein stenosis, following catheter
      ablation of atrial fibrillation, potentially carries significant morbidity for
      affected patients. It is important that physicians remain aware of the entity and
      have an understanding of how to treat such patients. There has been controversy
      in how to assess patients following atrial fibrillation ablation, and how to
      treat asymptomatic patients with pulmonary vein stenosis. This article reviews
      the recently published data. RECENT FINDINGS: The reported incidence of pulmonary
      vein stenosis is decreasing. Nonetheless, it may not be found if not sought, as
      even patients with severe pulmonary vein stenosis may be asymptomatic. Also,
      patients with symptoms may be misdiagnosed if pulmonary vein stenosis is not
      included in the differential diagnosis. Computed tomography (CT) and MRI have
      been shown to be the diagnostic modalities of choice. The treatment options for
      severe pulmonary vein stenosis and occlusion are primarily that of pulmonary vein
      angioplasty with or without stenting. Despite the observed rate of restenosis,
      patients derive benefit from pulmonary vein angioplasty. SUMMARY: The best
      imaging modalities to assess for pulmonary vein stenosis are CT and MRI. Early
      intervention in symptomatic patients with severe pulmonary vein stenosis is
      warranted; in asymptomatic patients, the data suggest that such patients will
      also derive benefit.

PMID- 19102038
TI  - Vasovagal syncope: state or trait?
AB  - PURPOSE OF REVIEW: The absence of a satisfactory comprehensive theory for
      vasovagal syncope has prompted attention towards a possible genetic origin. There
      are several features of this trait that suggest a genetic origin. The purposes of
      this review are to present a rationale for considering a genetic origin and
      critically summarize recent findings. RECENT FINDINGS: Key characteristics that
      suggest a genetic origin are incomplete effect in the population, a persistent
      clinical phenotype, and the absence of obvious infectious or autoimmune causes.
      There are familial pedigrees of vasovagal syncope, and statistical analyses of
      the impact of family history on the likelihood of an individual fainting that
      suggest an autosomal dominant transmission with incomplete penetrance. There is
      also evidence of sex-specific penetrance. Early candidate gene studies point
      towards involvement of sympathetic signal transduction in the physiologic
      cascade. SUMMARY: Several epidemiologic characteristics of vasovagal syncope
      suggest that it may have a genetic origin.

PMID- 19102039
TI  - Clinical spectrum of patients with a Brugada ECG.
AB  - PURPOSE OF REVIEW: The Brugada syndrome continues to spark intensive
      investigation since its earliest description. New insight has been gained
      regarding the genetic, histopathologic, and metabolic mechanisms of this
      heritable channelopathy - a heterogeneity that is reflected in the diverse
      clinical presentation. In this review, we will focus on clinical spectrum of
      patients with a Brugada ECG pattern with a special focus on diagnosis and risk
      stratification. RECENT FINDINGS: In the past year, multiple case reports have
      demonstrated that the Brugada ECG pattern is not limited to those with the
      diagnosed syndrome, with increasing evidence that an 'overlap' exists among
      inherited channelopathies, especially those involving the sodium and calcium
      channels. SUMMARY: The clinical spectrum of patients with a Brugada ECG remains
      broad, reflecting the heterogeneity of the underlying pathophysiology. As the
      true prevalence of the disease unfolds, knowledge regarding the clinical spectrum
      of patients with a Brugada ECG is important to implement effective risk
      stratification and management. It may be proposed that the ECG pattern of ST
      segment elevation in the right precordial leads should not be seen as a marker of
      a specific syndrome, but rather as a common electrical expression of structural
      abnormalities in the right ventricle that may have genetic, infective, or
      inflammatory origins.

PMID- 19102041
TI  - Current world literature. Degenerative and cognitive disease.

PMID- 19102040
TI  - Bridge or continue Coumadin for device surgery: a randomized  controlled trial
      rationale and design.
AB  - PURPOSE OF REVIEW: Many patients requiring cardiac arrhythmia device surgery are
      on chronic oral anticoagulation therapy. The periprocedural management of their
      anticoagulation presents a dilemma to physicians, particularly in the subset of
      patients with moderate-to-high risk of arterial thromboembolic events. Physicians
      have responded by treating patients with bridging anticoagulation while oral
      anticoagulation is temporarily discontinued. However, there are a number of
      downsides to bridging anticoagulation around device surgery; there is a
      substantial risk of significant device pocket hematoma with important clinical
      sequelae; bridging anticoagulation may lead to more arterial thromboembolic
      events and bridging anticoagulation is expensive. RECENT FINDINGS: In response to
      these issues, a number of centers have explored the option of performing device
      surgery without cessation of oral anticoagulation. The observational data suggest
      a greatly reduced hematoma rate with this strategy. Despite these encouraging
      results, most physicians are reluctant to move to operating on continued Coumadin
      in the absence of confirmatory data from a randomized trial. SUMMARY: We have
      designed a prospective, single-blind, randomized, controlled trial to address
      this clinical question. In the conventional arm, patients will be bridged. In the
      experimental arm, patients will continue on oral anticoagulation and the primary
      outcome is clinically significant hematoma. Our study has clinical relevance to
      at least 70 000 patients per year in North America.

PMID- 19102042
TI  - Current world literature. Neoplasms.

PMID- 19102043
TI  - Adult height in Turkish patients with Turner syndrome without growth hormone
      treatment.
AB  - Spontaneous adult height (AH) in Turner syndrome (TS) varies among populations.
      Population-specific AH data is essential to assess the efficacy of growth
      promoting therapies in TS. A multicenter study was performed to establish AH of
      nongrowth hormone (GH)-treated Turkish patients with TS. One hundred ten patients
      with TS (diagnosed by karyotype) who reached AH (no growth in the previous year,
      or bone age > 15 years) without receiving GH treatment were included in the
      study. The average AH was found to be 141.6 +/- 7.0 cm at the age of 22.9 +/- 6.2
      years, which is 18.4 cm below the population average and 16.4 cm below the
      patients' mid-parental heights. Bone age at start of estrogen replacement was
      12.3 +/- 1.3 year. Karyotype distribution of the patients was 45X (43%), 45X/46XX
      (16%), 45X/46Xi (12%), 45XiXq (10%) and others (19%). When the patients were
      evaluated according to their karyotype as 45X and non-45X, no significant
      difference in AH was observed (142.4 +/- 6.9 cm vs 140.9 +/- 7.1 cm,
      respectively). Adult height of non-GH-treated Turkish TS patients obtained in
      this study was comparable to that of other Mediterranean populations, but shorter
      than that of Northern European patients. Karyotype does not seem to affect AH in
      TS.

PMID- 19102044
TI  - Characteristics of relevance for health in Turkish and Middle Eastern adolescent
      immigrants compared to Finnish immigrants and ethnic Swedish teenagers.
AB  - Our objective was to compare sociodemographic conditions and risky/health
      behaviors affecting Turkish or Middle Eastern versus ethnic Swedes and Finnish
      immigrant adolescents, respectively. All eligible adolescents 13-18 years old
      (3,216 pupils) in a medium-sized town in Sweden completed a validated in-depth
      questionnaire (Q90), with 165 questions. One hundred and one adolescents were
      Turkish or Middle Eastern immigrants, while 73 were immigrants from Finland, a
      neighboring country to Sweden. Turkish/Middle Eastern immigrants were more likely
      to attend a theoretical program in school, were rarely bullied, as compared to
      ethnic Swedes and Finns. Turkish/Middle Eastern girls used alcohol at a lower
      frequency, and reported less depression and sexual experiences than ethnic
      Swedish girls and Finns. A higher frequency of Finnish adolescents had been
      bullied and had vandalized, and Finnish adolescents were also determined to have
      used tobacco and cannabis and to be heavy drinkers more frequently than boys from
      Turkey/the Middle East. We concluded that adolescent immigrants from Turkey and
      the Middle East seem to be well adapted to Sweden and also have ambitions for a
      higher education. Differences in risky behaviors were particularly pronounced in
      comparisons with immigrants from Finland for both boys and girls.

PMID- 19102045
TI  - Lamotrigine in children with refractory epilepsy.
AB  - We studied the efficacy and side effect profile oflamotrigine (LTG) in children
      with intractable epilepsy. We reviewed the database of our prolonged video-EEG
      laboratory to screen patients with intractable epilepsy who were on LTG either
      alone or in combination for three months or more. Of 75 patients, 28 patients
      (37%) had primary generalized seizures, 42 patients (56%) had partial onset
      seizures with or without secondary generalization, and 5 patients (7%) had two or
      more types of seizures. LTG reduced seizure frequency by at least 50% in 57.1% of
      patients with partial seizures and in 53.6% of patients with primary generalized
      seizures. The incidence of adverse events was relatively low (15%); the most
      common was skin rash. LTG should be considered in the treatment of pediatric
      patients with both partial onset and primary generalized seizures refractory to
      the major older antiepileptic drugs. LTG has a favorable side effect profile.

PMID- 19102046
TI  - Detection of TT virus (TTV) by three frequently-used PCR methods targeting
      different regions of viral genome in children with cryptogenic hepatitis, chronic
      B hepatitis and hbs carriers.
AB  - This study was designed so that three sensitive and widely-used polymerase chain
      reaction (PCR) methods for the detection of TT virus or Torque Teno virus (TTV)
      would be simultaneously applied to a large number of subjects to evaluate
      performances of the various PCR protocols with different genotype sensitivities.
      Sera were collected from 92 children admitted to Hacettepe University Ihsan
      Dogramaci Children's Hospital Pediatric Gastroenterology Unit (17 cryptogenic
      chronic hepatitis, 17 asymptomatic HBs carriers, 18 chronic HBV patients and 40
      healthy children). TTV DNA was detected via nested N22, nested 3'-UTR and 5'-UTR
      PCRs for all samples. Differences in TTV D N A detection prevalences were n o t
      statistically significantbetween the study groups with all TTV DNA and liver
      enzyme levels. A significant agreement between PCR methods that target UTR was
      observed. TTV detection rate increased with age, suggesting a non-parenteral,
      environmental exposure to the virus for the study population.

PMID- 19102047
TI  - Neutrophil hypersegmentation in children receiving angiotensin converting enzyme
      inhibitors.
AB  - Captopril and enalapril are the most commonly used angiotensin converting enzyme
      inhibitors in several cardiac diseases in children. On the other hand, the
      intrinsic renin-angiotensin system in the bone marrow might affect the growth of
      hematopoietic colonies and cellular production, proliferation and differentiation
      in physiological and pathological states. Starting with the hypothesis that
      inhibition of the renin-angiotensin system may have some effects on the
      hematopoietic system, including morphological changes within the granulocytes, we
      thus aimed to investigate prospectively whether the use of angiotensin converting
      enzyme inhibitors has any effect on the morphology, and especially segmentation,
      of neutrophils in peripheral blood. A total of 40 children with various heart
      diseases receiving either of two angiotensin converting enzyme inhibitors
      (captopril or enalapril) aged between 2 to 16 years were enrolled, and 40 healthy
      age- and sex-matched children were enrolled as controls. Complete blood count,
      peripheral blood smear, liver and renal function tests, and measurement of serum
      alkaline phosphatase, ferritin, vitamin B12 and folate levels were performed in
      all cases. Peripheral blood smears were viewed by two pediatric hematologists in
      a blinded manner. Neutrophil hypersegmentation was described as presence of five
      or more neutrophils with five well-separated lobes or at least one neutrophil
      with six or more lobes among 100 segmented neutrophils. The number of patients
      with neutrophil hypersegmentation in the study group was significantly higher
      than in the control group, and the mean lobe count in the study group was
      significantly higher than in the control group. Neutrophil hypersegmentation, as
      detected in patients using angiotensin converting enzyme inhibitors in the
      present study, has not been reported previously. Further studies aiming to
      explain the pathophysiological mechanism(s) underlying neutrophil
      hypersegmentation in patients receiving angiotensin converting enzyme inhibitors
      are needed.

PMID- 19102048
TI  - Association of Campylobacter jejuni infection and GuillainBarre syndrome: a
      cohort study in the northwest of Iran.
AB  - Recent studies have suggested that Campylobacter jejuni is a common pathogen
      causing Guillain-Barre syndrome (GBS). This study aimed to determine the
      frequency and clinical and electrophysiological features of C. jejuni infection
      in children with GBS. We carried out a prospective study on a cohort of 48
      children with GBS admitted to Tabriz Children's Hospital in the northwest of Iran
      from January 2003 to March 2005. Serologic investigations were used to diagnose
      preceding C. jejuni infection. Evidence of a recent C. jejuni infection was found
      in 23 (47.9%) of the patients. C. jejuni-associated GBS patients were younger
      than others (p = 0.010), and they had a rapid progression to reach peak
      disability (p = 0.018). Neither the peak disability nor the residual one-year
      disability was different between the C. jejuni- positive and C. jejuni-negative
      patients. The patients with preceding C. jejuni infection were more likely to
      have axonal neuropathy (p = 0.021).

PMID- 19102049
TI  - Nonconvulsive status epilepticus during childhood: clinical and
      electroencephalographic features.
AB  - Nonconvulsive status epilepticus (NCSE) is a medical emergency, which is
      diagnosed most frequently with the routine use of EEG in the pediatric emergency
      and intensive care units. Data from eight patients, ranging from 2.8-15 years old
      (median 8.7 years), treated with the diagnosis of NCSE were evaluated on clinical
      basis. The patients attended the hospital with acute confusional state ranging
      from sudden onset of verbal cooperation insufficiency to aimless-meaningless
      behavior and confusion without any motor component of seizure. While five of the
      cases were diagnosed and followed up with epilepsy, the other three had no
      history of epilepsy. No reason was detected that could cause acute
      encephalopathy. EEG examinations during acute confusional state showed partial or
      generalized continuous electrographic seizure activity lasting at least 30
      minutes without clinical seizure activity. After administration of intravenous
      antiepileptic medication, the confusional states of the patients recovered, and
      the EEG examinations showed normal baseline activity with significantly
      diminished discharges or complete normal waveform. Nonconvulsive status
      epilepticus should be considered in all children admitted to the hospital with
      acute unexplained encephalopathy, whether they have a history of epilepsy or not.
      Emergent EEG examination should be a routine part of evaluation in these children
      for the diagnosis and treatment of NCSE.

PMID- 19102050
TI  - The joint use of human and electronic eye: visual assessment of jaundice and
      transcutaneous bilirubinometry.
AB  - Our aim was to study the usefulness of jaundice visual assessment combined with
      skin bilirubin determination in 517 healthy newborns. Yellowness assessment was
      made and babies were included in three different bilirubin classes. Skin
      bilirubin and total serum bilirubin were determined within 10 minutes from the
      visual assessment. This latter led to underestimation of serum bilirubin in 16.7
      40.4% and overestimation in 4.9-35.7% of newborns. Skin bilirubin measurement
      after the visual assessment decreased the risk of underestimation to 0-9.2% and
      the risk of overestimation to 2.1-11.1%. The majority of visual assessment errors
      were performed in the more lighted hours of the morning (75%), while the smallest
      number (39%) occurred during the afternoon. Skin bilirubin measurement
      significantly corrected these diagnostic errors (p < 0.001, p < 0.02) without
      differences during the day. Clinical estimate is unreliable for evaluating the
      need for serum bilirubin assay. Using the addition of skin bilirubin
      determination is a more advisable approach.

PMID- 19102051
TI  - The frequency of autoimmune thyroid disorders in juvenile idiopathic arthritis.
AB  - Few studies have been performed to investigate autoimmune diseases associated
      with organ non-specific rheumatological disorders in children, such as juvenile
      idiopathic arthritis (IA). The objective in this study was to determine the
      frequency of autoimmune diseases of the thyroid gland in children with JIA.
      Eighty patients with JIA and 81 healthy sex- and age-matched controls were
      enrolled in the study. Serum free T3, free T4, thyroid stimulating hormone (TSH),
      anti-thyroglobulin antibodies, and anti-peroxidase antibodies were evaluated. The
      mean age was 11.5 +/- 5.5 years in the patient group and 10.5 +/- 4.9 years in
      the control group. Twenty-seven of the cases were classified as oligoarticular,
      26 as polyarticular, 17 as enthesitis-related, 6 as systemic, and 4 as psoriatic
      arthritis. Autoimmune thyroid disease was found in 4 patients in the JIA group
      (5%). There were no significant differences between the study and control groups
      regarding the existence of anti-thyroid antibodies (p = 0.17). Girls were more
      likely to develop autoimmune thyroiditis (3 girls, 1 boy). Autoimmune thyroiditis
      was more frequent in patients who had a family history of thyroid disease (p =
      0.02). There was no statistical correlation between rheumatoid factor (RF) and
      antinuclear antibody (ANA) positivity and autoimmune thyroiditis (p > 0.05). We
      conclude that there is no need for routine screening of serum thyroid function
      tests and thyroid antibody levels in patients with JIA in the absence of clinical
      symptoms.

PMID- 19102052
TI  - Perinatal features and umbilical cord blood gases in newborns complicated with
      nuchal cord.
AB  - Presence of nuchal cord (NC) is associated with transient decrease of umbilical
      cord blood flow. However, the exact perinatal effect of presence of NC in a
      newborn is still under debate. The aim of this study was to evaluate the
      perinatal complications and umbilical cord blood gases of deliveries complicated
      with NC and summarize the associated literature. Gestational age-matched term
      singleton pregnancies complicated with NC (n=160) were compared with neonates
      without NC (n=160). Patients' files and Labor and Delivery Unit database were
      used to extract maternal age, gestational age, presence of NC, number of nuchal
      loops around fetal neck, intrapartum complications and umbilical cord blood
      gases. pH, pO2, pCO2, HCO3-, O2 saturation, and base excess were determined in
      all patients. Mean maternal age, mean gestational age, and birth weight were not
      significantly different between the two groups (p > 0.05). Occurrence of
      oligohydramnios, intrauterine growth retardation (IUGR), intrapartum
      abnormalities and Apgar scores < 7 at 1 minute were not significantly different
      between the groups (p>0.05). However, umbilical cord blood pH (7.32 vs. 7.30, p =
      0.048), pO2 (37.4 +/- 18.1 vs. 31.7 +/- 14.4, p = 0.01) and O2 saturation (57.4
      +/- 21.8 vs. 48.3 +/- 20.4, p = 0.005) were significantly lower in the NC group
      compared with the controls. Furthermore, the number of Apgar scores < 7 at 1
      minute was significantly higher in neonates with multiple NC (28.1% vs. 9.2%, p =
      0.007), and intrapartum abnormalities were more frequently seen in newborns with
      multiple NC (31.3% vs.15.6%, p = 0.04). The results of this study suggest that
      presence of single NC may negatively affect the umbilical cord blood gases
      without significant perinatal complications. However, multiple NC may also
      increase the development of intrapartum complications and lower Apgar scores.
      Perinatal effects of NC should be investigated with a large prospective study.

PMID- 19102053
TI  - Ataxia with vitamin E deficiency associated with deafness.
AB  - Ataxia with vitamin E deficiency (AVED) is a rare autosomal recessive disorder,
      usually with a phenotype resembling Friedreich ataxia, caused by selective
      impairment of gastrointestinal vitamin E absorption. Vitamin E supplementation
      improves symptoms and prevents disease progress. In North Africa and Southern
      Europe, AVED is as common as Friedreich ataxia. There are no reported cases from
      Turkey. We herein report a 16-year-old Turkish girl with AVED, who was found to
      have total deletion of the TTPA gene as well as sensorineural deafness, and we
      present her follow-up data after vitamin E therapy.

PMID- 19102054
TI  - Vomiting as the initial clinical presentation of myocardial infarction in
      children with anomalous left coronary artery from the pulmonary trunk.
AB  - Anomalous origin of the left coronary artery from the pulmonary trunk is a rare
      condition. The clinical presentation is usually nonspecific and varies from
      completely asymptomatic form to sudden cardiac death. We report a two-month-old
      infant with vomiting as a presenting symptom of anomalous origin of the left
      coronary artery from the pulmonary trunk.

PMID- 19102055
TI  - Acute respiratory distress for late-presenting congenital diaphragmatic hernia.
AB  - Congenital diaphragmatic hernia (CDH) presents a wide spectrum of anatomical
      variants and clinical pictures depending on the topography and dimensions of the
      diaphragmatic defect and on the patient age. Most CDH cases acutely present with
      tachypnea, cyanosis, and respiratory failure within the first minutes to hours of
      life. Despite significant advances in neonatal medicine, this congenital anomaly
      still presents a high mortality rate, especially for associated malformations. On
      the other hand, there is a rare subset of CDH patients who present outside the
      neonatal period. The most common symptoms of late-presenting CDH include
      recurrent pulmonary infections, dyspnea, wheezing, abdominal pain, failure to
      thrive, vomiting, diarrhea and anorexia. Although late-presenting CDH generally
      presents good prognosis after early surgical correction, misdiagnosis is quite
      frequent because of its wide spectrum of clinical manifestations. The following
      case report describes a six-month-old infant presenting with acute respiratory
      distress and vomiting caused by late-presenting left-sided CDH.

PMID- 19102056
TI  - A rare cause of hyperbilirubinemia in a newborn: bilateral adrenal hematoma.
AB  - Hyperbilirubinemia is an important health problem in newborns. The most common
      causes are Rh and ABO incompatibility, hemolytic anemias, enzyme deficiencies,
      sepsis, hypothyroidism, pyloric stenosis and breast-milk jaundice. Adrenal
      hemorrhage is a rare cause of hyperbilirubinemia in the neonate. We present a six
      day-old newborn with hyperbilirubinemia and suprarenal hematoma who was born at
      home without assistance of healthcare personnel. Adrenal hematoma should also be
      considered in the differential diagnosis of hyperbilirubinemia, particularly in
      newborns that experienced a difficult delivery.

PMID- 19102057
TI  - Enterohemorrhagic Escherichia coli O157:H7: case report.
AB  - Enterohemorrhagic Escherichia coli (EHEC) is a significant bacterial pathogen of
      bloody diarrhea. Not only does it cause systemic complications, such as hemolytic
      uremic syndrome (HUS) (the most common cause of potentially preventable pediatric
      renal failure), but it also leads to large outbreaks of bloody diarrhea. Among
      EHEC serotypes that cause HUS, E. coli O157:H7 is the most common. Herein, we
      present the case of a young girl with E. coli O157:H7 infection and review the
      related literature.

PMID- 19102058
TI  - Restrictive dermopathy: report of one case and the metabolic and post-mortem
      findings.
AB  - Restrictive dermopathy is a rare and lethal autosomal recessive genodermatosis
      characterized by tight skin, typical dysmorphic face, generalized arthrogryposis
      and pulmonary hypoplasia. Infants with restrictive dermopathy have similar
      findings in skin biopsy, but other abnormalities are unremarkable. We report a
      male preterm infant with restrictive dermopathy. The post-mortem examination
      revealed hypoplasia of the thymus, and the metabolic study of the urine and blood
      disclosed generalized organic aciduria and low free carnitine level. These data
      imply that restrictive dermopathy is associated with certain degrees of metabolic
      disturbance. With increasing reports of restrictive dermopathy, the affected
      infants can be diagnosed earlier and accurately.

PMID- 19102059
TI  - Desmoplastic infantile ganglioglioma: case report.
AB  - Desmoplastic infantile gangliogliomas are very rarely encountered, large
      supratentorial masses, derived from neuroepithelial origin, which have cystic and
      solid components and contain cells with astrocytic and ganglionic
      differentiation. These tumors are benign tumors of childhood that become
      symptomatic when they reach giant sizes. Sixty cases of desmoplastic
      ganglioglioma have been reported to date. In the present study, a case of giant
      desmoplastic infantile ganglioglioma in a 22-month-old patient is presented,
      which had an aggressive radiological appearance in the midline and presented with
      atypical symptoms.

PMID- 19102060
TI  - Quadricuspid aortic valve: a rare cause of aortic regurgitation and stenosis.
AB  - Quadricuspid aortic valve is a rare congenital condition that occurs not only as
      an isolated anomaly, but also with other cardiac defects. We describe a 10-year
      old boy whose aortic stenosis was diagnosed during infancy. Transthoracic
      echocardiography revealed dilation of the left ventricle, valvular and
      subvalvular aortic stenosis, bicuspid aortic valve, aortic regurgitation, and
      mitral valve prolapse. The results of cardiac catheterization and aortography
      showed severe aortic regurgitation, an aortic valve gradient of 76 mmHg, a
      bicuspid aortic valve, a subaortic membrane, and an ascending aortic aneurysm.
      The patient underwent elective valve replacement with a mechanical prosthesis,
      and during surgery, the valve was noted to be quadricuspid. The patient was
      diagnosed as having a quadricuspid aortic valve associated with aortic
      regurgitation, severe aortic stenosis, and an ascending aortic aneurysm.

PMID- 19102061
TI  - Minimally conjoined omphalopagi: emphasis on embryogenesis and possibility of
      emergency separation.
AB  - Minimally conjoined omphalopagus twins (MCOTs) has been recognized in the last
      decade as a special subgroup in which omphalopagus twins have union of peritoneal
      cavities through anterior lower abdominal wall defect with union of distal small
      intestine and patent urachal structures and associating anorectal malformation. A
      careful review of the current literature revealed that MCOTs have usually been
      separated in emergency situations within the first hours of life due to ruptured
      omphalocele, gastroschisis, stillbirth of one of the twins, intestinal
      obstruction, or requirement of enterostomy for cloacal anomaly. Pediatric
      surgeons should be familiar with MCOTs and ready for emergency separation with
      thorough knowledge of the anatomical relationships of the connecting structures
      and the embryologic basis for this anomaly. We present a new set of MCOTs
      separated in emergency conditions with a review of the relevant English
      literature. We give special emphasis to the common surgical characteristics and a
      brief discussion on the embryogenesis of this rare condition.

PMID- 19102062
TI  - Kidney stone and urinary bladder telangiectasia in a patient with TAR syndrome.
AB  - TAR syndrome is a congenital malformation syndrome characterized by bilateral
      absence of the radius and thrombocytopenia. The known urinary anomalies are
      duplex ureter, dilatation of renal pelvis, horseshoe kidney and functional
      problems like vesicoureteral reflux and pyelonephritis. In this report of a case
      with TAR syndrome, a kidney stone and bladder telangiectasia were found
      coincidentally during the investigation of hematuria. TAR syndrome is discussed
      in the light of the medical literature. To our knowledge, no case has been
      reported demonstrating nephrolithiasis and bladder telangiectasia in TAR
      patients.

PMID- 19102063
TI  - Kidney disease in acute hemorrhagic edema of young children.

PMID- 19102064
TI  - Are antibiotics required for the treatment of acute serous otitis media in
      children?

PMID- 19102065
TI  - Quality of life research in patients suffering from tension type headache.
AB  - The tension type headache is the most common headache type, which many men and
      women suffer from in one period of their life and aggravates business
      productivity, family and social functioning. Quality of life estimation in
      patients suffering from tension type headache enables us to get a better insight
      into the impact of the disease on the patient. The comparison among the quality
      of life in the patients suffering from tension type headache and the quality of
      life in the control group subjects has been carried out in a research by applying
      the QVM questionnaire. The obtained results have shown a significant difference
      in the quality of life and its sub domains indicating worse quality in the
      patients suffering from tension type headache.

PMID- 19102066
TI  - [The acute effects of 3,4-methylenedioxymethamphetamine on oxidative stress in
      rat brain].
AB  - INTRODUCTION: Oxidative stress and oxygen free radicals are thought to play an
      important role in acute effects of a number of neurotoxic processes. 3,4
      Methylenedioxymethamphetamine (MDMA, ecstasy), a ring substituted amphetamine
      derivate, has attracted a great deal of media attention in recent years due to
      its widespread abuse as recreational drug by the young generation. The aim of the
      present study was to evaluate the acute effects of 3,4
      methylenedioxymethamphetamine on oxidative stress parameters (index of lipid
      peroxidation--ILP, superoxide radicals O2-, superoxide dismutase--SOD and
      glutathione--GSH) in frontal cortex, striatum and hippocampus in Wistar rats.
      MATERIALS AND METHODS: The study included 40 male Wistar rats (200-250 g), housed
      4 per cage having free access to food and water. MDMA was dissolved in
      distillated water and administered peroraly at 5, 10, 20 or 40 mg/kg. 8 hours
      following MDMA, the rats were killed by decapitation, their brains were rapidly
      removed and the brain structures were dissected out on ice and analyzed
      biochemically. RESULTS: Acute peroral administration of a single dose (5, 10, 20
      and 40 mg/kg) resulted in increase of ILP, O2-, SOD and decrease of GSH.
      CONCLUSION: The results obtained in the present study suggest that oxidative
      stress plays a crucial role in MDMA-induced neurotoxicity and that the mechanism
      of MDMA neurotoxicity may vary between brain regions.

PMID- 19102067
TI  - [Work stressors among physicians with and without the acquired cardiovascular
      disorders: assessment using the Occupational Stress Index].
AB  - The Occupational Stress Index (OSI) questionnaire for physicians was used in a
      case-control study, with a high participation rate (> 90%). The study was carried
      out among physicians employed at clinical institutions in Novi Sad, receiving
      their medical care at the health center situated within the Novi Sad clinical
      center. The cases were physicians with one or more of the acquired (potentially
      stress-related) cardiovascular disorders (ACVD) (myocardial infarction, angina
      pectoris, arterial hypertension and certain arrhythmias). The control group
      included physicians without manifest ACVD. Two OSI dimensions: high demands (p <
      0.05) and threat avoidance (p < 0.05) were dominant in showing significantly
      higher exposure levels among the cases. The most consistent and significant
      stressors that distinguished the physicians with ACVD from the referents were
      long work hours, speed-up and threat of job loss. Personality patterns were not
      associated with case status. Physicians are a heavily burdened occupational
      group, and several occupational stressors are significantly associated with case
      status. Improvements in working conditions as well as early diagnosis are
      essential for preventing further increases in these disorders among physicians.
      The next step would be multidisciplinary intervention studies aimed at the work
      environment, with the goal of identifying scientifically-based strategies that
      are most effective in preventing ACVD among physicians.

PMID- 19102068
TI  - [Morphometric characteristics of neuropeptide Y immunoreactive neurons of human
      cortical amygdaloid nucleus].
AB  - INTRODUCTION: Cortical amygdaloid nucleus belongs to the corticomedial part of
      the amygdaloid complex. In this nucleus there are neurons that produce
      neuropeptide Y. This peptide has important roles in sleeping, learning, memory,
      gastrointestinal regulation, anxiety, epilepsy, alcoholism and depression.
      MATERIAL AND METHODS: We investigated morphometric characteristics (numbers of
      primary dendrites, longer and shorter diameters of cell bodies and maximal radius
      of dendritic arborization) of NPY immunoreactive neurons of human cortical
      amygdaloid nucleus on 6 male adult human brains, aged 46 to 77 years, by
      immunohistochemical avidin-biotin technique. RESULTS: Our investigation has shown
      that in this nucleus there is a moderate number of NPY immunoreactive neurons.
      67% of found neurons were nonpyramidal, while 33% were pyramidal. Among the
      nonpyramidal neurons the dominant groups were multipolar neurons (41%--of which
      25% were multipolar irregular, and 16% multipolar oval). Among the pyramidal
      neurons the dominant groups were the neurons with triangular shape of cell body
      (21%). All found NPY immunoreactive neurons (pyramidal and nonpyramidal
      altogether) had intervals of values of numbers of primary dendrites 2 to 6,
      longer diameters of cell bodies 13 to 38 microm, shorter diameters of cell bodies
      9 to 20 microm and maximal radius of dendritic arborization 50 to 340 em. More
      than a half of investigated neurons (57%) had 3 primary dendrites. DISCUSSION AND
      CONCLUSION: The other researchers did not find such percentage of pyramidal
      immunoreactive neurons in this amygdaloid nucleus. If we compare our results with
      the results of the ather researchers we can conclude that all pyramidal NPY
      immunoreactive neurons found in this human amygdaloid nucleus belong to the class
      I of neurons, and that all nonpyramidal NPY immunoreactive neurons belong to the
      class II of neurons described by other researchers. We suppose that all found
      pyramidal neurons were projectional.

PMID- 19102069
TI  - Surgical treatment of the supraglottic laryngeal carcinoma.
AB  - This is a retrospective analysis of 439 patients with supraglottic laryngeal
      cancer primary surgically treated in the period 1976-1999. The objectives of our
      study were to analyze the localizations as well as local and regional tumor
      spread, frequency of occult and palpable cervical metastases, the incidence of
      local and regional recurrences, five-year survival rate and functional results of
      supraglottic partial horizontal laryngectomies. A retrospective analysis of
      operated patients was carried out. T1 tumor was prevalent in 184 (42%) patients,
      T2 in 228 (52%) patients, and T3 tumor in 27 (6%) of cases. Clinically negative
      finding of the neck was found in 369 (84%) patients, and metastasis N1 was
      established in 70 (16%) patients. The patients with clinically negative cervical
      finding underwent selective neck dissection, while N1 metastasis patients were
      subjected to a selective or modified radical neck dissection. Five-year disease
      free survival rate was 76% (334/439).

PMID- 19102070
TI  - [Influence of fibrinolitic potential reduction in ischemic brain disease
      development].
AB  - INTRODUCTION: Vascular brain disease are the third leading cause of morbidity and
      mortality today. Among them ischemic brain disease caused mostly by cerebral
      atherosclerosis makes almost 80%. The main risk factors for this disease are
      arterial hypertension, dislipoproteinemia and diabetes but, recently hemostatic
      system disorders have also been underlined, especially fibrinolytic disorders.
      PHYSIOLOGY OFFIBRINOLYSIS: The primary role of fibrinolytic system is to make
      blood vessels passable by prevention of thromb forming or by removing the
      existing ones. This role is enabled by constant dynamic balance between
      activators and inhibitors of fibrinolysis. The leading activators are tissue
      plasminogen activator (t-PA) and urokinase plasminogen activator (u-PA) and the
      most important inhibitors are 2-antiplasmin, plasminogen activator inhibitor 1
      (PAI-1) and thrombin activated fibrinolytic inhibitor (TAFI). FIBRINOLYSIS AND
      THROMBOSIS: In patients with atherosclerosis there is clear insufficiency of
      fibrinolysis caused mainly by the increased activity of fibrinolytic inhibitors.
      There is evidence that the level of PAI-1 connected to fibrin directly affects
      thromb resistance to fibrinolysis and that velocity of thromb lysis in vitro
      predominantly depends on TAFI concentration. Factor XIII also has influence on
      thromb structure and stability and Lp(a) lipoprotein is one more factor that is
      responsible for resistence of thromb to fibrinolysis. FIBRINOLYSIS IN ISCHEMIC
      BRAIN DISEASE: Reduced fibrinolytic capacity is noticed in patients with ischemic
      brain disease resulting from the increased PAI-1 activity. Higher risk for
      ischemic brain disease is veryfied among people with 4G/4G PAI-1 genotype. Raised
      level of t-PA anti-gene can also induce reduction of endogenous fibrinolysis.
      CONCLUSION: In conclusion we want to underline that a possible pathophysiological
      significance of fibrinolytic system is assumed in a high percentage of patients
      with ischemic brain disease. Because of that we need further investigations to
      establish precise role of fibrinolytic mechanisms in genesis of this disease.

PMID- 19102071
TI  - [Endogenous anticonvulsants: neuropeptide Y and delta sleep inducing peptide].
AB  - INTRODUCTION: The same neuropeptides regulate both cicle sleep-wake and
      excitability of the brain. CONCLUSION: Literature data together with our results
      support the idea that delta sleep--inducing peptide and neuropeptide Y could
      represent one of the factors of the endogenous stabilization of brain
      excitability and potent antiepileptic in generalized metaphit-induced audiogenic
      convulsive activity. The same holds true for DSIP analogues.

PMID- 19102072
TI  - [Cardiovascular risk factors in workers at health centre in Beocin].
AB  - Most cardiovascular diseases are caused by atherosclerosis, which is a result of
      interactions between risk factors such as gender, age, blood lipid
      concentrations, blood pressure, glucose tolerance, adiposity, physical activity
      and cigarette smoking. Identification of risk factors is the first step in
      cardiovascular disease prevention. As health workers contribute significantly to
      cardiovascular morbidity, the aim of our study was to analyze prevalence of
      cardiovascular risk factors and to assess the level of mentioned risk in health
      workers employed in Health Centre Beocin. The study group consisted of 50 health
      workers. Obesity was evaluated according to BMI and body fat (BF%) values, while
      central obesity was defined using waist circumference. Serum lipid concentrations
      and glycaemia were used in metabolic profile definition. The level of physical
      activity was assessed using IPAQ, and information about smoking status and family
      history of cardiovascular diseases was obtained from self-report. Framingham
      point-scoring system was used to predict the risk for development of coronary
      heart disease in the 10-year period. Overweight was found in 36%, and obesity in
      18% subjects. 42% of examined subjects had higher fat mass, while 24% of them had
      obesity. Central fat accumulation was observed in 50% subjects. We registered 56%
      smokers, 70% subjects with positive family history, 28% subjects with
      hypertension, and 56% subjects with dyslipidemia. According to IPAQ results 20%
      of examinated subjects were minimally active and 70% were insufficiently active.
      Estimated risk of coronary heart disease was 7.38%, and 10% subjects had risk
      over 20%. In spite of lower cardiovascular risk level, our results showed high
      prevalence of overweight, smoking and physical inactivity in health workers,
      which suggests take importance of their own lifestyle modification. It should be
      the first step in increasing motivation of their patients.

PMID- 19102073
TI  - [Coagulase-negative Staphylococcus isolated from bloodculture--causes or
      contaminants?].
AB  - INTRODUCTION: According to the results of different investigations, the opinion
      that isolate of coagulase-negative staphylococci by bloodcultures represents the
      blood infection in 10-12% patient. The aim of the work was to determine the
      number of patients with blood infection-sepsa induced coagulase-negative
      staphylococci isolated by bloodcultures. MATERIAL AND METHODS: The research was
      done at the Institute for Public Health in Nis. The basic group consisted of 56
      patients and coagulase-negative staphylococci were segregated form their
      bloodcultures. The growth of microorganisms was monitored by the computerized
      apparatus "Bactec 9120". Coagulase-negative staphylococci were identified by the
      standard microbiologic method and Vitec AMS system. RESULTS: Eight patients
      (14.28%) were found to have minimum two signs of blood infection. S. epidermis
      was isolated in four patients. S. saprophyticus was isolated in the patients on
      hemodialysis with implanted urinary catheter. S. capitis was isolated in the
      patients with infarctus miocardi. S. auricularis was isolated in child who was
      administered the immunosuppressive therapy before and during hospitalization due
      to an acute asthmatic attack. The isolate of S. simulans was cultivated from
      samples of the patients hospitalized due to the febrile state. DISCUSSION: A
      correct interpretation of coagulase-negative staphylococci findings in
      bloodcultures is an overriding part of medical treatment. The best laboratory
      indicators of the presence of coagulase-negative staphylococci in blood would be
      to segregate those of the same kind from two samples at the same time but from
      different anatomic sites in the presence of clinical signs of blood infection.
      CONCLUSION: In the investigation conducted at the Public Health Institute-Nis, we
      determined that bloodcultures isolated coagulase-negative staphylococci represent
      the blood infection on 14.28% patient.

PMID- 19102074
TI  - [Therapy of lupus nephritis with mycophenolate mofetil].
AB  - INTRODUCTION: Mycophenolate mofetil is an immunosuppressive agent used in
      transplantation and subsequently in a variety of autoimmune conditions. It
      inhibits both B and T lymphocyte proliferation, and also has nonimmune effects on
      the kidney. The major experience in systemic lupus erythematosus has focused on
      proliferative lupus nephritis. MATERIALS AND METHODS: In our study we treated 8
      female patients having proliferative lupus nephritis with combination therapy of
      prednisone (1 mg/kg body weight) and mycophenolate mofetil (2 g per day).
      Complete remission was defined as a value for urinary protein excretion that was
      less than 0.5 g per 24 hours, with normal urinary sediment, a normal serum
      albumin concentration and improved or stable serum creatinine. Partial remission
      was defined as a daily proteinuria below 2g in the previously nephrotic patient
      or minimum 30% from starting values, with normal urinary sediment, serum albumin
      of minimum 30 g/L and stable serum creatinine. RESULTS: Two patients had a
      complete remission after 7 and 2 months respectively. Five patients had a partial
      remission after 5.2 +/- 4.3 months of therapy. One patient did not react to
      therapy. There were no side effects during the course of therapy. DISCUSSION:
      Considering the fact that 7/8 patients have had nephrotic range proteinuria and
      that 50% of patients were refractory on standard induction therapy, the results
      of this study are a good indicator of value of mycophenolate mofetil in the
      therapy of proliferative forms of lupus nephritis. CONCLUSION: Mycophenolate
      mofetil has satisfactory results in the treatment of proliferative forms of lupus
      nephritis with minimal side effects.

PMID- 19102075
TI  - [Changes and variations of body weight as risk factors for coronary heart
      disease].
AB  - INTRODUCTION: Weight variations are a common phenomenon. Therefore, concern has
      been raised about the association between weight changes and weight variations
      and coronary heart disease (CHD). The aim of this study was to estimate the
      influence of weight change and weight variations as risk factors for coronary
      heart disease. MATERIALS AND METHODS: The investigation was conducted as an
      observational cross-sectional study, including 102 participants of both genders:
      61 patients with CHD and 41 healthy controls. All participants underwent
      anthropometric measurements and completed a questionnaire that included 1) weight
      changes in adulthood (maximum and minimum weight), 2) presence and number of
      weight variations in the 10 years prior to the onset of disease and 3) the size
      of weight change (weight gain or weight loss in kg). One weight variation was
      defined as weight loss followed by weight gain for more than 10% of body weight,
      or about 7 kg. Multivariant logistic regression was used for the estimation of
      significant predictors for the occurrence of coronary heart disease. RESULTS:
      Participants with CHD had higher values of body weight in adulthood compared to
      healthy controls, larger number of weight variations in the last 10 years, and
      more frequently reported weight gain and weight loss for more than 10 kg. The
      highest risk for the occurrence of coronary heart disease was observed for
      participants who had more than 3 weight variations for 10% (OR = 2.13; 95% CI =
      0.98-5.48), those with weight loss over 10 kg (OR = 2.16; 95% CI = 1.71-2.72) and
      those with weight gain over 10 kg (OR = 2.71: 95% CI = 1.08-6.83), regardless of
      gender, age, smoking, body mass index and blood pressure. DISCUSSION: Several
      mechanisms are suggested to explain the relationship between weight changes and
      variations and coronary heart disease, including changes in plasma lipid levels,
      insulin levels. decrease of HDL cholesterol, increase of C-reactive protein and
      increase of blood pressure. CONCLUSION: This study suggests that frequent and
      very intense weight changes can be considered important predictors for the
      occurrence of coronary heart disease.

PMID- 19102076
TI  - [Correlation between neurological finding and gestational maturity of newborns
      determined by neurosonography].
AB  - INTRODUCTION: Maturity is a complex functional condition influenced especially by
      the development of the vital functions of a fetus, primarily by the degree of the
      development of its central nervous system. The aim of this investigation was to
      establish the gestational maturity of the nervous system by neurosonography and
      neurological status. MATERIAL AND METHODS: The parameter of the neurological
      maturity, compared in this research are a neurological status and the degree of
      girification established by the ultrasound. RESULTS: All the coefficients of
      correlation between the gestation age determined by the ultrasound and the
      establishing of the gestation based on the neurological findings show a
      statistically significant correlation for p < 0.01. Of particular parametres of
      the neurological evaluation , the most appropriate ones appeared to be reflexes
      (the reflex of crossed extension, Moro reflex and the reflex of the main points),
      then volar flexion of a hand and the poplietal corner as the indicator of the
      passive tonus, whereas within the area of the evaluation of the active tonus, the
      motility was the most valid for establishing the maturity of a neonatal. The
      lowest coefficients of the correlations were in the automatic walk and the active
      tonus of the neck flexor, which are the ones of the most common neurological
      indicators of hypoxic ischemic encephalopathy of a neonatal. CONCLUSIONS: Bearing
      in mind that the premature babies are a risky group for existence of perinatal
      brain damages, we believe the neurosonographic establishing of the gestation age
      to be a precise and comfortable indicator of the maturity of the nervous system.

PMID- 19102077
TI  - [Evaluation, treatment and evolution of Broca's aphasia].
AB  - This paper presents the evaluation treatment and improvement of a patient with
      Broca's aphasia. A specific form of speech therapy, based on the peculiarities of
      the clinical picture of Broca's aphasia, was applied during one year. Our results
      have shown that this form of therapy leads to a significant improvement of the
      communicative abilities, even in the cases with severe form of aphasia. The
      importance of application of the specific methods and therapies for the
      rehabilitation of aphasic patients is pointed out.

PMID- 19102078
TI  - [Cholestatic syndrome in patients with systemic erythematous lupus--differential
      diagnostic aspects].
AB  - Systemic lupus erythematosus is a multisystemic inflammatory disease with diverse
      clinical manifestations. Hepatic lesion is a rarely seen complication of systemic
      lupus erythematosus. We report a case of complication of lupus presented as
      cholestatic syndrome in a 41-year old woman with lupus in her medical history for
      the past seven years. A general examination showed jaundice and hepatomegaly,
      with elevated bilirubin and aminotransferase levels in the liver function tests.
      The liver biopsy was performed and the microscopic examination revealed
      cholestasis with bile plugs without any signs of inflammation and liver tissue
      necrosis. After the three months steroid therapy the clinical symptoms resolved
      and the laboratory values normalized. The various factors are considered to be
      involved in the ethiopathogenesis of liver damage. Previous treatment with
      potentially hepatotoxic drugs (imuran in this case) or viral hepatitis have
      usually been implicated as the main cause of liver disease in lupus patients. On
      the other hand, even after careful exclusion of these ethiologies, the problem
      remains whether to classify the patient as having a primary liver disease with
      associated autoimmune and laboratory features resembling lupus, or as having a
      liver disease as a manifaestaion of lupus.

PMID- 19102079
TI  - [Recurrent respiratory infections with severely damaged lung functions-
      Kartagener's syndrome--case report].
AB  - INTRODUCTION: Kartagener's (or Siewert) syndrome represents a clinical
      presentation of primary ciliary diskinesia (PCD) with 3 dominant symptoms:
      bronchiectasiae, chronic sinusitis and situs viscerum inversus totalis or
      dextrocardia, only. Siewet demonstrated the first case of this clinical
      phenomenon in 1904, which was recognized by Kartagener in 1933, as a congenital
      disorder. PCD is an autosomal recessive disease with extensive genetic
      heterogenity. Dyskinetic or completely absent motiliy of cilia predisposes to
      recurrent pulmonary and upper respiratory tract infections resulting in
      bronchiestasis. Also, infections of the middle ear are common due to lack of
      ciliary movement in the Eustachian tube. Men have reduced fertility due to
      spermatozoa with absent motility or abnormalities in the ductuli efferentes. CASE
      REPORT: Our case report represents a middle age woman, treated ambulatory for
      many years as a chronic obstructive pulmonary disease (COPD). The patient noted
      recurrent upper respiratory tract infections from her childhood, headaches and
      recurrent sinusitis. Also, she had extrauterine pregnancy, no children, in spite
      of several arteficial inseminations. Due to the clinical signs of the right heart
      failure and the described ECG changes, the echocardiographic examination was
      done, which showed the dextracardia and the ultrasonographic examination of the
      abdomen revealed the situs inversus, the finding being within the physiological
      limits. CONCLUSION: All data regarding situs viscerum invesrus, supported by CT
      verification of bronchiectasiae and chronic inflammation of maxillar sinus led us
      to conclude that the patient suffered from Kartagener's syndrome.

PMID- 19102080
TI  - [County doctors in Senta from 1876 to 1941].
AB  - In the introduction of this paper the authors review the legal rules which
      regulated the institution of a county doctor and their legal obligations. The
      introduction also gives the insight into the social environment in Senta, a town
      with its organized senate. The research included the period from 1876 to 1941.
      The Historical Archives were searched for the data about the county doctors
      working there in this period. The data for the period 1919-1941 were so scarce
      that the authors were obliged to go through the local newspapers in order to get
      any, very often meagre, information. Although some very important data are
      missing for some of the doctors, these doctors are listed here in order to enable
      further research. The first officially registered county doctor in Senta was Dr
      Laslo Zingor, who held that post until April 28, 1887. Prior to his arrival to
      Senta, Dr Janos Remai Nepomuki, the town doctor, had probably performed the duty
      of the county doctor. In the period from 1876 to 1941 the following doctors
      worked in Senta as county doctors: Dr Laslo Zingor, Dr Antal Strilic, Dr Jozef
      Havel, Dr Lipot Kovac, Dr Andor Senes, Dr Borivoje Djordjevic, Dr Vladislav
      Matejic, Dr Jovan Miskovic, Dr Radmilo Lj. Jankovic-Ozrenac, Dr Miloje Josipovic,
      Dr Vasilije Golubovic and Dr Mihajlo Romanenko. The above biographies are
      enriched by the photos of the doctors, advertisements and other texts taken from
      various local newspapers.

PMID- 19102082
TI  - [Medical Society remobilizes].

PMID- 19102083
TI  - [Allergies in ENT].
AB  - Allergy is quite frequent and ENT syptoms are usually the visible part of a
      general disease. Questioning remains the most important part of the enquiry for
      clinical examination is usually poor if notdesapointing. Biological testings
      detailed in this paper may be of some help; In Africa, test-treatements using
      cheap and unharmfull drugs give often the best evidence of allergy. Seldom, ENT
      allergy may be or become life-threatening. Its detection and appropiate actions
      are briefly mentioned.

PMID- 19102084
TI  - [Contact dermatitis in Dakar].
AB  - Because of the widespread repartition of allergens, allergic contact dermatitis
      is the most common inflammatory skin disease. It's the best model of dilated
      hypersensibility mediated by T lymphocytes cells. Atopic dermatitis and
      irritative dermatitis are to be distinguished to contact dermatitis. The
      aetiological diagnosis is the most important step of management of patients with
      that disease because it's the best way to avoid recurrences. The identification
      of cause is based on aetiological interrogatory and epicutaneous tests with 23
      allergens completed with personnel products and specialised tests. Contact
      dermatitis can be classified according to results of aetiological management. In
      occupational contact dermatitis, contact dermatitis due to drugs, to metals,
      cosmetics, clothes and accessory and proteins. Management of patients with
      contact dermatitis is based on individual eviction, protection, cosmetovigilance,
      declaration of occupational dermatosis and allergovigilance.

PMID- 19102085
TI  - [A systemic approach to the diagnosis and treatment of allergic conjunctivitis].
AB  - The diagnosis of allergic conjunctivis begins by a meticulous questioning
      emphasizing the existence of ocular itching, the way of evolution of the signs
      and allergic preceeding. The examination searchs after follicles and papillae of
      the conjunctiva who usually go with serous discharges, blepharitis and keratitis.
      So four clinical forms may be described the chronic conjunctivitis, the vernal
      kerato-conjunctivitis, the atopic conjunctivitis and the giganto-papillar
      conjunctivitis. For the treatment, all non specific signs of allergy must be
      eliminated, the focal infections also and allergic substance isolated. If
      evolution is worse, an antiallergic eye drop is given until the disappearance of
      all the physical signs. In the same time, steroids and anti H1 drugs must be
      avoided. In case of failure, the specialist in allergy will be helpful to exam
      the patient.

PMID- 19102086
TI  - [Ultrastructural aspects of the spermatozoon abnormalities on infertile men in
      Senegal].
AB  - Oligo-astheno-teratozoospermia being frequently observed (44,1%) in male subjects
      among hypofertiles couples of the sample population, we studied it at the
      ultrastuctural level. Our investigations have shown that, in addition to
      morphological and functional abnormalities, spermatic cells in said persons also
      presented serious ultrasructural disorders which would cause sterility. However
      in the absence of specific codified treatment for the majority of abnormalities
      found in sperms and given the high cost of the utrastructural analysis, we
      propose to limit our study to precise cases of male sterility through routine
      sample evaluations.

PMID- 19102087
TI  - [Lupus nephritis in Senegal: study of 42 cases].
AB  - INTRODUCTION: Renal involvement determines the prognosis of systemic lupus
      erythematosus. The aims of this study were to precise clinical, laboratory,
      therapeutic and evolutive aspects of lupus nephritis in Senegal in order to
      improve its management. PATIENTS AND METHODS: According to ACR criteria we
      included all patients presenting a systemic lupus erythematosus followed in
      internal medicine and in the dermatology services of university teaching hospital
      Aristide le Dantec of Dakar from January 1993 to December 2002. All the patients
      who didn't have a lupus nephritis defined by the existence of more than 0.5 g/24
      h of proteinuria and or hematuria were excluded. RESULTS: The prevalence of lupus
      nephritis was 56.75% among 74 patients with systemic lupus erythematosus. Mean
      age was 29.6 years and sex ratio 0.13 (male to female). There was a nephritic
      syndrome in 45.23% of the cases and renal insufficiency in 37.71%. Renal biopsy
      performed in 52.38% of cases showed predominantly WHO classes IV and V. The key
      treatment was corticotherapy while immunosuppressive were used in 35.71%. The
      short term evolution was favourable but in the medium term, many patients were
      lost or followed up irregularly. CONCLUSION: To improve the management and the
      prognosis of lupus nephritis in Senegal it is necessary to make patients with a
      systemic lupus erythematosus sensitive to it and to make systematically urine
      tests aiming the screening for an early diagnosis of lupus nephritis. In addition
      we should have aggressive policies in order to lower the costs of
      immunosuppressive therapy and haemodialysis.

PMID- 19102088
TI  - [Culture and characterization of porcine coronary endothelial cells].
AB  - INTRODUCTION: Vascular endothelium possesses biological properties that are
      involved in important physiological functions such vascular permeability,
      vascular tone regulation and angiogenesis. The difficulty of culture and long
      term maintenance of sufficient amount of normal endothelial cells has proven to
      be the limitation for the understanding of the biological function of the
      endothelium. Therefore, the aim of this study was to culture and characterize the
      porcine coronary endothelial cells. MATERIAL AND METHODS: The endothelial cells
      were isolated by collagenase treatment and cultured in culture dishes coated with
      collagen, prepared from rat tail, containing medium RPMI1640/M199 and 15% fetal
      calf serum supplemented with antibiotics and fungizon. The cells were maintained
      to grown at 37 degrees C. The medium was changed one day after and then every two
      day. The cells were incubated with Dil-labeled-acetylated-LDL for determination
      of acetylated-LDL uptake. Confluence cultures of cells were examined by phase
      contrast and confocal microscopy. RESULTS: After a day of culture, the
      endothelial cells adhere to the collagen and began to grow. While multiplying
      themselves, they colonize little by little the body of the surface of culture to
      form to confluence a monolayer of flat cells relatively homogenous. To
      confluence, the proliferation of the endothelial cells is inhibited by the
      contact and the cells present a polygonal aspect. Our results show that all the
      cultivated cells were strongly positive for acetylated-LDL markers. The
      endothelial cells, cultivated until the second passage corresponding to the
      second culture of the primary cultures, continued to present a good fluorescence.
      CONCLUSION: Porcine coronary endothelial cells represent a useful in vitro model
      to study biological and physiopathological properties of vascular endothelium.

PMID- 19102089
TI  - [Actualities in extrinsic allergic alveolities or hypersensitivity pneumonitis].
AB  - Significant advances have been noticed in the pathogenesis and the diagnosis of
      extrinsic allergic alveolitis during the last few years. Indeed the immune
      mechanism and the enabling conditions have been more precisely defined, the
      clinical stages and the diagnosis criterias clearly defined, new antigens
      incriminated and some etiological agents have been reclassified. The present
      pathogenic explanation insists on the type IV hypersensitivity reaction with
      sensitization of T lymphocytes, activation macrophages, the formation of IgG type
      antibodies and immune complexes, activation of complement and secretion of
      cytokines. The involvement of certain HLA classes (HLA2, DR3, DRB1, DQB1),
      interaction of genetics and environments factors, the role of infections agents
      and smoking have been demonstrated in several studies. The development of news
      clinical and biological diagnosis criteria have led the discovery of new
      extrinsic allergic alveolitis in the work places, a better knowledge of the
      prognostic elements and an appropriate adaptation of prevention measures.

PMID- 19102090
TI  - [Undesirable effects of methothrexate during treatment of rheumatoid arthritis].
AB  - INTRODUCTION: Methotrexate used as antimetabolite since 40 years in cancerology,
      is curretly pointed out at weak dose in the treatment of rheumatoid arthitis.
      However, the intervening of undesirable effects is currently the principal factor
      limiting its use. The main of our study was evaluate the nature and the frequency
      of undesirable effects during treatement of rhumatoid arthritis by methotrexate
      in a prospective study in the department of internal medecine of A.L.D hospital.
      MATERIAL AND METHODS: Fifty patients were included in the study, they were 43
      female and 7 male (sex ratio of 0.161).The mean age were 40.8 years, ranging from
      18 to 68. The mean last of MTX treatment was 16.58 months, ranging from 1 to 64.
      RESULTS: Twenty seven patients (54%) had at least one undesirable effect.
      Undesirable effect appeared early in 74.1%. they were 61.5% when MTX was
      associated with others drugs versus 27.3% when MTX was used alone. Undesirable
      effects mostly were digestives (38%), general (30%), mucouscutaneous (8%) and
      hepatics (2%).for patients undesirable effects had involved. They were
      responsable of definitive stopping treatment in two cases of pulmonary
      tuberculosis.

PMID- 19102091
TI  - [Antiphospholipid antibodies syndrome in dermatology in Dakar: 11 case report].
AB  - INTRODUCTION: Our aim was to report the cutaneous features of antiphospholipid
      antibodies syndrome in Dermatology in Dakar. METHODS: Our study was retrospective
      from January 2000 to December 2001. All patients were diagnosed according to the
      criteria of the international consensus statement in 1999 on the antiphospholipid
      antibodies. RESULTS: Eleven cases (all female) were collected with a median age
      of 28 years. A systemic lupus was associated in 7 cases, a scleroderma in 1 case
      and mix connectivity in 1 case. The dermatological manifestations found in all
      patients were necrosis of the extremities (4 cases), purpuric lesions (4),
      cutaneous ulcers (3), acrocyanosis (2), livedo (1) and subungual splinter
      hemorrhage (1). The obstetrical incidents were noted in 82% of cases; there were
      precocious and repeated abortions (in 5 cases), foetal loss (in 4 patients),
      precocious delivery (in 2 cases), lateness of growth in uterus (in 1 case). It
      was an arterial thrombosis in 2 cases. The mean level of anticardiolipin
      antibodies was 60 UGPL and a dissociation of the syphilitic serology was present
      in 9 patients. A severe thrombopenia in 1 case was observed. The evolution was
      favorable in 7 patients. In other cases, we noted foetal loss in 2 cases and
      distal necrosis relapse in 2 cases. CONCLUSION: Cutaneous manifestations are
      diverse. They can be lupus involvements or microcirculatory thrombosis and they
      make the diagnostic easy.

PMID- 19102092
TI  - [Analize of the determinants of microscopy's quality in the context of
      tuberculosis fighting within the health centers laboratories in Dakar Region].
AB  - INTRODUCTION: In order to improve the quality of the microscopy in the context of
      tracking and following-up the pulmonary tuberculosis patients, a study of the
      determinants of the quality of microscopy was carried out in the laboratories of
      the health centres in Dakar Region, Senegal. MATERIALS AND METHODS: We did an
      epidemiologic study, transversal type which proceeded during April 19th at May
      05th, 2004. It consisted of a series of observations, interviews, review of the
      registers of laboratory and with a second reading and re staining, on the level
      of the National Laboratory of Reference of the National Programme of fight
      against Tuberculosis (LNR), of 50 blades collected blindly in the health centres
      of Dakar. RESULTS: It comes out from this study that there was no statistically
      significant link between the factors of risk of errors such as the overload of
      work, the bad condition of the microscope, the lack of competence and the errors
      observed in certain laboratories. On the other hand the aspect of the smears, the
      thickness of the smears and the presence of crystals could deteriorate the
      quality of microscopy because it was found that there was a statistically
      significant connection between the quality of microscopy and these various
      determinants. In addition we noted a good agreement of the results of these
      laboratories with those of the LNR (Kappa test = 0,981, p < 0,0001). CONCLUSION:
      According to these results, we recommend: a reinforcement of competences
      (training/recycling) regular of the laboratory assistants, and an installation of
      a system of quality control of microscopy, interns within the laboratories but
      also external by the National Laboratory of Reference.

PMID- 19102093
TI  - [Clinical and endoscopic features of solitary rectal ulcer syndrom in the
      digestive endoscopy unit of Hospital Aristide Le Dantec in Dakar].
AB  - INTRODUCTION: The solitary rectal ulcer syndrome is a rare disease. In Africa
      only few studies have been held on this subject. The aim of this study was to
      determine the epidemiological, clinical and endoscopic aspects of this syndrome
      in the digestive endoscopy unit of hospital Aristide Le Dantec in Dakar. PATIENTS
      AND METHOD: It was a retrospective study based on all the cases of solitary
      rectal ulcer regarding to the conclusion of endoscopic examination from January
      1994 to June 2002. All the patients without histological confirmation were
      excluded. RESULTS: We had recruited 11 cases among 4250 endoscopic exam (0.26 %).
      The mean age was 40 years (extreme 23 to 63 years). Female to male ratio was 1.75
      with 4 males and 7 females patients. The main indications of endoscopic
      examination were frequently associated and were dominated by intermittent
      bleeding (8 cases) chronic constipation (6 cases) and false chronic diarrhea with
      muco hemorrhagic discharge (4 cases). The mean duration of the symptoms was 5
      years. Ulcers were ovoid or circular. Their mean diameter was 8 mm and they were
      located 8 cm above the anal margin. The lesion was unique in 55 % of the cases
      and concerned the anterior wall of the rectum in 74% of the cases. There was an
      internal rectal prolapse in 54% of the cases. CONCLUSION: The solitary rectal
      ulcer syndrome is not frequent in the endoscopy unit of hospital Aristide Le
      Dantec in Dakar. It affects mostly young adult female. The symptoms are chronic
      and non specific. In tropical areas the disease is frequently misdiagnosed as
      colic amoebiasis.

PMID- 19102094
TI  - [Stroke and phenylpropanolamine: what risk factors and what recommendations in
      request?].

PMID- 19102095
TI  - [Evaluation of serological tests of toxoplasmosis in pregnant women realized at
      the Laboratory of Parasitology and Mycology of Le Dantec Teaching Hospital in
      2002].
AB  - INTRODUCTION: the toxoplasmosis can occur complications during pregnancy as
      serious repercussions on the foetus with the risks linked to this pathology such
      as abortion. However these complications can be avoided during the pregnancy by
      an early diagnosis. The objective of this study is to determine the prevalence of
      toxoplasmosis during pregnancy. MATERIALS AND METHODS: we undertook this study on
      109 pregnant women addressed to the laboratory of parasitology and mycology of
      the CHU Dantec for toxoplasmosis serological test on 2002. We used a
      immunoenzymatic technical in solid phase whose principle rests on the change of
      coloration in the presence of antibody of IgM or IgG; coloration whose intensity
      is function of the title of antibody. For that, two serological tests (S1 and
      S2), starting from two venous blood at 3 weeks of interval, are carried out among
      these pregnant women. This second serology will make it possible to confirm or
      cancel an evolutionary toxoplasmosis based on the variation of the title in
      antibody between the first (S1) and the second serology (S2). A control is
      carried out among these women among whom the diagnosis of the evolutionary
      toxoplasmosis was established. RESULTS: they show that with the first (S1), from
      the 109 patients, 3% were positive with the antibodies IgM type, 22% positive
      with IgG, and 11% positive with IgG and IgM. 36% of the women present a positive
      diagnostic at the first serology (S1). The second serology (S2) shows that among
      the 36% of the women diagnosed positive with the first serology, 11% made an
      evolutionary toxoplasmosis. CONCLUSION: This study shows a rather significant of
      serological toxoplasmosis discovered fortuitously among pregnant women at the
      time of their assessment of pregnancy.

PMID- 19102096
TI  - [Advantages of laparoscopic assisted vaginal hysterectomy in surgery of
      endometrial carcinoma].
AB  - INTRODUCTION: In to respect the principles of oncological surgery and to reduce
      the operative morbidity, the authors of this study propose to find the proper
      place of the laparoscopic-assisted vaginal hysterectomy in the surgery of
      endometrial carcinomas. PATIENTS AND METHODS: Between the 1st of June 2002 and 31
      of May 2005, we realize a retrospective and comparative study for 36 laparoscopic
      assisted vaginal hysterectomy and 20 laparotomies concerning 56 patients.
      RESULTS: In primary stages (stages I and II of FIGO), laparoscopic assisted
      vaginal hysterectomy is as powerful as the laparotomy whereas in more advanced
      stages, laparotomy was more complete and effective (p=0,07). One conversion case
      was observed (2.8%) in a context of peritoneal carcinosis (stage IIIc). There was
      not statistically significant difference about the operatives complications (p =
      0.51). On the other hand, the postoperative comfort was so far better in the
      laparoscopic-assisted vaginal hysterectomy group (p=0.0002). The average delay of
      followed without relapses was 22,3 months in the laparoscopic-assisted vaginal
      hysterectomy group versus 23 months in the laparotomy group (p=0.51). CONCLUSION:
      Considering these results, the authors retain that, in primary stages (I-II,
      FIGO), laparoscopic-assisted vaginal hysterectomy represents a real option in the
      surgery of endometrial carcinoma. On the other hand, the advanced stages should
      be reserved for laparotomy.

PMID- 19102097
TI  - [Nosocomial infections: definition, frequence and risk factors].
AB  - Infection is nosocomial if it missed at the time patient admission in the health
      establishment. When infectious status of the patient on admission is unknown,
      infection is generally regarded as nosocomial if it appears after a time of at
      least 48 hours of hospitalization. For surgical site infection, the commonly
      allowed time is 30 days, or, in case of prosthesis or an implant, one year after
      surgical intervention. Nosocomial infections (NI) constitute major health care
      problem from their frequency, their cost, their gravity. Mortality related to NI
      can attempt 70% in certain units like intensive care units. Two ways of
      contamination are possible: the endogenous way is responsible of majority of
      hospital infections. The normally sterile sites are contaminated then colonized
      by the flora which is carrying the patient himself, with the favor of a rupture
      of the barriers of defense. The exogenic way is associated colonization, possibly
      followed by infection, of the patient by external bacteria, coming from others
      patients or from environment, transmitted in an indirect way (aerosols,
      manuportage, materials). Whatever its mode of transmission, apparition of
      nosocomial infection can be related to several supporting factors: age and
      pathology, certain treatments (antibiotic which unbalance patients' flora and
      select resistant bacteria, immunosuppressive treatments), invasive practices
      necessary to the patient treatment. The prevalence of nosocomial infections is
      higher in the intensive care units where certain studies bring back rates of
      42.8% versus 12.1% in others services. The four sites of nosocomial infection
      most frequently concerned are: the respiratory site, urinary infections,
      bloodstream infections (Catheters related bloodstream infections in particular),
      and surgical sites infections. The relative proportion of these infections varies
      according to principal activity of the unity.

PMID- 19102098
TI  - [Nosocomial infections: main causative agents].
AB  - INTRODUCTION: Nosocomial Infections acquired within a care unit, may be related
      to various agents (Bacteria, virus, fungi, parasites...). The study purpose is to
      give relevent data on the main causative agents. MAIN AGENTS: The authors have
      shown the prevalent role of bacteria, mainly Enterobacteria, Staphylococcus and
      Pseudomonas; Legionella is also frequently isolated in some countries.
      Multiresistant Bacteria could be sometimes associated to nosocomial infections
      and severe infections. Among Nosocomial Virus: VRS, Rotavirus, Hepatitis B and C
      Viruses, HIV, Influenza Virus are cited. Fungal Agents (Aspergillus, Candida),
      Plasmodium, Non Conventional Agents (Prions) are also causative agents of
      Nosocomial Infection. CONCLUSION: The Isolation of contagious Agent in a
      hospitalized patient is not the only criteria for Nosocomial Infection typing;
      Rigorous analysis needed to be done for every case.

PMID- 19102099
TI  - [Preventive measures and the strife against nosocomial infection].
AB  - The nosocomial Infections are associated to an increase of the morbidity, of the
      mortality and costs. Their frequency stay on raised in our service of cares. Then
      it is recommended and broadly admitted what each hospital must dispose of a unity
      of nosocomial infections prevention and to dispose a staff specially vested in
      those duties. Of the fact the nosocomial infections frequency in reanimation, an
      imported part of the activity of this specialized staff will have to run out in
      services of intensive cares. The principal nosocomial infections feature observed
      is being directly or indirectly associated to engineerings of acting as invasives
      deputy used to palliate a vital lapse. Of a general manner, all sharp grave
      affection, as anything severe traumatism (accidental or surgical) drag a
      capacities reduction of defense against the infection, component so important
      factors of nosocomial infections installations. Preventive measures pass by the
      engineerings respect of hands hygiene, the harbour of clean conformable dress,
      the measures respect of isolation (septic or preventive), the cares grading, the
      upkeep of the hardware and the bedroom, the respect of the circuit of the linen
      salts and lastly the sorting and the losses management of activity of cares. For
      that it must a policy of strife against nosocomial infections with the placing in
      place of operational unities of hygiene in all hospitals and the redynamisation
      of the committee of strife against nosocomial infections already existed in
      different public establishments of health.

PMID- 19102100
TI  - [Epidermodysplasia verruciformis: clinicaland epidemiological features of 45
      cases in the Department of Dermatology at the University Hospital Center of
      Yalgado Ouedraogo, Ouagadougou].
AB  - INTRODUCTION: The epidermodysplasia verruciformis is a rare, autosomic,
      recessive, genodermatose characterized by a chronic, disseminated, cutaneous
      infection with human papillomavirus. The majority of these patients have a
      genetic or acquired immunodeficiency. PATIENTS AND METHODS: This retrospective
      study was conducted on the records of all patients who presented in our
      dermatology department with an epidermodysplasia verruciformis in a 13 years and
      6 months period, from January 1st, 1992 to June 30th, 2005. RESULTS: We have
      collected 45 cases of epidermodysplasia verruciformis. They were aged from 3 to
      57 years, with a mean of 24.6 years. The most concerned age bracket was that from
      zero to 9 years. They were 29 women (64.4%) and 16 men (35.6%). The eruption
      presented as papules of 2 to 3 mm size, associated with hypochromic, finely
      squamous macules with the same size. We noted three cases of itching. We found
      37.7% of family cases. We observed 14 cases of HIV positive patients and one case
      of cancer. CONCLUSION: This study confirmed that the epidermodysplasia
      verruciformis was rare. Genetic factors or immunodeficiency would support the
      appearance of the disease.

PMID- 19102101
TI  - [Elephantiasic pretibial myxoedema: study of five cases].
AB  - INTRODUCTION: Elephantiasic myxoedema is very rare. We report 5 pretibial
      myxoedema cases observed in the Dermatological department of Le Dantec hospital
      in Dakar. PATIENTS AND METHODS: Our 5 cases were 3 women (age: 52, 45 and 18
      years) and 2 men (age: 54 and 32 years). RESULTS: All the cases were enormous,
      multinodular pachydermic, bilateral, elephantiasis in the low leg and associated
      to Graves 'disease. The duration was 4 month to 12 year. In 3 cases there was a
      Diamond syndrome which is a severe form. The cutaneous lesions were not
      influenced by medical treatment of thyroid disease. Systemic steroids achieved
      improvement of the elephantiasis in 1 case. CONCLUSION: Elephantiasis is a very
      unusual presentation of pretibial myxoedema and its occurrence doesn't depend to
      the intensity of thyrotoxicosis and its evolution. However in our cases, it was a
      severity indicator factor, like Diamond syndrome. Local and systemic steroids
      give very rarely improvement.

PMID- 19102102
TI  - [Von Willebrand disease and menorrhagia].
AB  - INTRODUCTION: Known since over than seventy years, von willebrand disaese is the
      most common herediary bleeding disorder. This condition was first described by
      Pr. Willebrand in 1926 in a family with (positive) history of excesive bleeding
      tendency. Von Willebrand desease is characterized by a lifelong tendency toward
      easy spontaneous mucosal or post operative bleeding. In females, excessive or
      prolonged menorrhagia could be a sign of von willebrand desease; symptoms that
      are often misunderstood to be gynecologic rather than hematologic problem. In the
      present work, we have tried to screen for this anomaly in females with
      menorrhagia, following a simple anamnestic, clinical and biological protocol.
      PATIENTS AND METHOD: In a seventeen month study, fifty two procreating females
      with menorrhagia were recruited in the haematology laboratory of Aristide le
      Dantec hospital with the cooperation of gynecology and obstetric departements of
      Aristide Le Dantec, Abass Ndao and grand yoff Hospitals. RESULTS: Eight patients
      were revealed to be von willebrand positive (prevalence: 15%). The diagnosis was
      retained on the basis of epidemiological, clinical and biological data.
      CONCLUSION: These simple and accessible criteria should allow better handling of
      patients with hemorragic disorders.

PMID- 19102103
TI  - [Quality of malaria prevention during prenatal consultations in Niakhar
      (Senegal)].
AB  - INTRODUCTION: To evaluate the quality of malaria prevention during prenatal
      consultations, this study was carried out in Niakhar, one sub-prefecture of the
      Fatick region. METHOD: It was a matter of a descriptive transverse study, based
      on the listens and the observation of 60 prenatal consultations carried out
      within three health posts. The studied variables were related to the criteria of
      a good quality of prophylaxis at three levels: questioning, examination, and
      attitude after consultation. RESULTS: Questioning was centred by frequency order
      on: the pregnancy antecedents (65%), the chloroquine direction for use (34.3%),
      the fever notion (6%), and the chloroquine secondary effects (3%). During the
      physical examination, all the providers looked for clinical signs of weakens,
      blood pressure, and presence of oedemas of the legs; but the temperature was
      taken only in 8.6% of the cases. At the end of the consultation, the
      chemoprophylaxis prescription and the next consultation appointment were
      systematic; the duration of the treatment recalled in 57% and malaria seriousness
      during the pregnancy in 3% of the cases; no one of the providers didn't evoked
      neither the methods of the treatment nor the attitude to hold in case of fever.
      CONCLUSION: The prevention of the malaria in pregnancy through the CPN
      necessitates a fitting formation supported by regular supervision of the health
      posts.

PMID- 19102104
TI  - [Hyperthyroidism in surgery at the Teaching Hospital Yalgado Ouedraogo Burkina
      Faso. About 95 cases].
AB  - The authors pay in a retrospective study, 95 cases of hyperthyroidism, listed in
      the teaching hospital Yalgado Ouedraogo of Ouagadougou from January 2000 to June
      2005. These hyperthyroidism represent 39% of the thyroid affections, with a
      female prevalence (97%), 32 years of average age, the urban source of the
      patients (90% of the cases) and the importance of self medication (73%). They
      stress the importance of sonography, allowing a classification in diffuse goiter
      (44%) and multi nodular (56%). They insist on a good preparation of the patient
      before the intervention and on the interest of the sub total thyroidectomy. They
      estimate that a correct binding of the vessels, the dissection of recurring, the
      visualization and the dissection of parathyroid and their vascular pedicle should
      make it possible to reduce the post-operative complications: null morbidity and
      death rate 12.5%.

PMID- 19102105
TI  - [Costs of operation of an urban reinforced community health post (Senegal)].
AB  - INTRODUCTION: In Senegal, the public funding in community health post is low.
      Resources are mainly obtained from the sale of services. The aim of this study is
      to analyse the operating cost of a community health post and to propose a
      relevant tariffing that would assure sustainable activities. METHODS: We used the
      method of complete costs. It comes out from our study that the total cost is 20
      870 920F. RESULTS: Wages represent 70% of total expenses, operating costs
      represent 27% and 4% are investment. The public funding represents a value of 12
      257 325F (60% of the total) in which 88% correspond to expenses induced by civil
      servant wages. The health committee participates for 33% and the other
      participants (7%). CONCLUSION: At the end of our study, a sustainable and social
      tariffing, was proposed.

PMID- 19102106
TI  - [Etiological orientation from the analysis morphological and constitutional of
      urinary stones in Conakry].
AB  - INTRODUCTION: The epidemiological profile of urinary stones varies from region of
      the world to another according to food habit and certain enviromental factors.
      The aim of our study was to establish an etiological approach of the urinary
      lithiasis collected in Conakry by morphological and constitutional analysis.
      MATERIALS AND METHODS: It was a prospective study from january 1 rst 2003 to
      january 1 rst 2004 concerning all the stones collected. They were analysed by
      binocular magnifying glass and infra red spectrophotometry of Fourier. RESULTS:
      During the period, 18 patients were observed (14 male, 4 femele) of 27.4 +/- 4
      years old (from 2 to 69) living mainly in urban environment. From these patients
      28 stones were collected; 12 spontaneously and 16 surgicaly. Their composition
      were whewellite (36%), struvite (29%), carbapatite (14%), urates (14%) and
      weddellite (7%). In Conakry stones come mainly from hyperoxaluria and urinary
      tract infection; hypercalciuria is uncomon. CONCLUSION: The urinary calculations
      examined among patients show in the adult a prevalence of elements in favour of a
      hyperoxalurie and a notable context of urinary infections in particular in the
      child; the pure hypercalciurie remains negligible in Conakry, we plan to lead a
      thorough work to the national scales.

PMID- 19102107
TI  - [Experimental evidence of against cough activity of total alkaloids from Guiera
      senegalensis Lam. in guinea pig;].
AB  - INTRODUCTION: Against cough activity from Guiera senegalensis' leaves has been
      previously scientifically studied. However, to the best of our knowledge, active
      principles responsible of this activity were not yet identified. Thus, we
      undertook this work with the aim to evaluate the effect of total alkaloids from
      plant's leaves in cough induced in guinea pig by ammoniac inhalation. MATERIAL
      AND METHODS: Guinea pigs were divided up in 5 groups of 10 and were crammed with
      distilled water (control), total alkaloids with 10, 25 and 30 mg/kg and codeine
      with 50 mg/kg. They were then exposed to ammoniac inhalations and the number of
      coughs was counted every hour, after cramming, during 5 min. RESULTS: Our results
      show, after 5 hours, with the doses of 15, 25 and 30 mg/kg per os, that total
      alkaloids induce against cough activity, 2 hours after cramming (p < 0.01) and
      the difference was still significant 3, 4 and 5 hours after (p < 0.001). These
      alkaloids effects were comparable with codeine activity which was used as
      reference product. CONCLUSION: Total alkaloids of Guiera senegalensis present an
      against cough activity and would be responsible of against cough activity of the
      plant.

PMID- 19102108
TI  - [Toxic nodular goiter].
AB  - INTRODUCTION: To date no study in our country was specifically dedicated on toxic
      nodular goiter. They were just mentioned in generally studies about
      hyperthyroidism. METHOD: The authors report a retrospective series of 62 cases of
      toxic nodular goitre collected between 1979 and 1999 at the internal medical
      clinic of Dakar teaching hospital. The diagnostic of toxic nodule was retained on
      following criteria: to existence of one or several thyroid nodule with signs or
      thyrotoxicosis, the existence of a hyperfixating nodule at 131 iodine
      scintigraphy. Increasing of T3 and/or T4 thyroide hormone. The aims of the study
      was to analyse the epidemiological, clinical, and therapeutics aspects. RESULTS:
      We are collected 49 cases of solitary nodule (79.03%) and 13 cases of multi
      nodular goitre (20.97%). In the cases of solitary nodule, mean age was 40 years,
      sex ratio of 0.04 (47 female, 2 men). The nodule was clinically diagnosed in 47
      cases (95.9%) and extinctive in 73.5%. 34.3% of patients have cardiothyreosis. In
      the cases of multi nodular goitre mean age was 45 years, all cases were female,
      goitre was clinically identified in 95.3% (12 patients) and 46.5% had
      cardiothyreosis. 62% of patients were lost to follow up during medical treatment.
      Only 2 patients on the 37 who were addressed for surgery come back after
      thyroidectomy. CONCLUSION: This study confirm the predominance of toxic nodular
      goitre in young female, its severity related to cardiothyreosis and underlines
      the difficulties limited to the therapeutical care.

PMID- 19102109
TI  - [Clinical and psychopathological postpartum depression: eleven Senegalese cases
      report].
AB  - INTRODUCTION: The postpartum depression is a frequent puerperium psychiatric
      disorder. The authors study the clinical, therapeutic and evolutionary aspects of
      the postpartum depression among eleven Senegalese women. MATERIAL AND METHOD:
      They examined the medical reports and hospital registers of eleven patients
      belonging to a sample of 52 women presenting psychic disorders of the
      puerperality. The diagnosis was made by using the International Classification of
      the Diseases. RESULTS: The symptoms of depression were irritability, bad
      concentration, multiple somatic complaints, of insomnia of drowsiness, loss of
      the usual interests. All the patients profited from psychotherapy and have
      received chemotherapy with antidepressant treatment associated tranquillizing in
      six cases. They improved from 29 to 43 days after their admission. CONCLUSION:
      The pregnancy and the childbirth, the parity, personal history of the patient,
      their social environment and the cultural representations of maternity are
      factors of depression of the postpartum. The antidepressant is always essential
      in the treatment.

PMID- 19102110
TI  - [Arterial hypertension: epidemiological aspects and risk factors on pregnant and
      delivered woman].
AB  - OBJECTIVES: Determine frequency of hypertension in pregnancy and delivered women
      at the Teaching Hospital of Brazzaville and identify epidemiological aspects and
      risk factors. PATIENTS AND METHODS: A prospective and transversal study was
      realized from november 2004 to january 2005 in the Teaching Hospital of
      Brazzaville. Forty two patients (8 pregnant women, 34 delivered) with
      hypertension, have been enregistered among 825 admissions in the departments of
      gynecology and obstetric. Arterial hypertension was defined by a blood pressure
      at 140/ 90 mm Hg or above. RESULTS: Arterial hypertension constituted 5.1% of the
      total admissions. Average of the patients was 27 +/- 8 years (age range: 14 and
      40 years). Two patients (4.8%) haven't been sent to school, 29 (69%) had the
      secondary level, twenty (47.8%) were housewives. Seventeen patients (40.5%) had
      realized 2 prenatal consultations at the most. Patients were divided in 4 groups:
      Chronic hypertension (n = 4), pre eclampsia surimposed on chronic hypertension (n
      = 4), pregnancy hypertension only (n = 15), preeclampsia (n = 19). Prim gravidity
      (38.1%) and family history of hypertension (40.4%) were the most frequent risk
      factors. Obesity, gemality, previous pre eclampsia represented respectively
      14.3%, 9.5% and 4.8%.

PMID- 19102111
TI  - [Arterial hypertension and the kidney].
AB  - Arterial hypertension is a factor of major risk of cardiovascular complications
      which represent the first cause of death in the world. One can define it as a
      level of blood pressure (140/90 mmHg) beyond which the cardiovascular risk is
      important and requires a therapeutic action. One of the etiopathogenic
      assumptions selected is a disordered state of the relation pressure natriuresis
      wich is the major mechanism of control of long-term arterial pressure. The
      diagnostic means and of monitoring were the subject of consensus on the level of
      scientific societies what is not the case of the therapeutic strategy . In more
      of lifestyle change, the patients with renal diseases generally require an
      association of antihypertensive drugs whose the thiazide diuretics ones must have
      a leader place. Their association with ACE inhibitors or angiotensin receptor
      antagonists seem to give the best effectiveness in term of cardioprotection and
      nephroprotection.

PMID- 19102113
TI  - [Contribution of ATP-dependent potassium channels, nitric oxide and
      prostaglandins in increase of diaphgram arteriolar blood fow during diaphgram
      contraction].
AB  - ATP-sensitive potassium (K(ATP)) channels and nitric oxide (NO) have been
      suggested to contribute in mediating active hyperemia in diaphragm. However, no
      data is available in the current literature concerning their comparative
      contributions to arteriolar dilation during muscle contraction. The aim of this
      study was therefore to examine, by video microscopy in rats, the effects of
      superfusing the muscle with Krebs solution alone (group C), or Krebs solution
      containing either glybenclamide (3mdeltaM, a blocker of K(ATP), group GLY), or
      Nwdelta-nitro-L-arginine (300 mdeltaM, a NO synthase inhibitor, group NNA), or
      mefenamic acid (50 mdeltaM, a prostaglandin synthesis inhibitor, group MA) on
      second and third order of diaphragm (A2 and A3 respectively) arteriolar dilation
      elicited by 3 min muscle stimulation (40 Hz, train duration: 300 milliseconds, 90
      cycles per min). In group C, A2 diameters increased by 67.5 +/- 1.9% referring to
      baseline at the end of the stimulation. This increase was significantly reduced
      in groups GLY and NNA (16.7 +/- 2.5% and 47.3 +/- 2.2% respectively, p < 0.001 as
      compared to group C) and was more important in group GLY than in group NNA (p <
      0.001). By contrast, no difference in post-contraction diameter was observed
      between groups C and MA. Similar results were observed in A3 vessels. These
      results indicate that K(ATP) are more important mediators of functional diaphragm
      arteriolar dilation in rat than NO, whereas prostaglandins are not involved in
      this phenomenon.

PMID- 19102112
TI  - [The management of cerebrovascular events].
AB  - Strokes (AVC) represent the 1st cause of death in the department of neurology of
      Dakar. The main characteristic of stroke is the brutality of the method of
      formation of neurological deficit. The vascular territory in question amends the
      clinical expression. Besides the motor deficit stroke can cause
      neuropsychological disorders affecting language, memory, activity gesture,
      recognition of oneself and its environment, space and extra corporeal body with
      the result intellectual deterioration. The mechanisms of stroke are dominated by
      atherosclerosis and embolic heart disease for ischemic stroke and hypertension
      and ruptures of vascular malformations for hemorrhagic stroke. CT scan remains
      the key consideration in determining the nature ischemic or hemorrhagic stroke.
      Because of its acuteness and rapid progress to irreversible injury stroke is a
      dramatically high priority medical emergency. The therapeutic strategy should
      follow a pattern efficient and fast leading to a specific care, gradual and
      coordinated by the 3rd hour. There is a need to recognize stroke, what is the
      nature (ischemic, hemorrhagic) and the cause, in order to consider a therapeutic
      care consistent. The care must start at the very beginning of the stroke and
      continued during transportation. In the acute phase of stroke, lower blood
      pressure should be gradual and it is recommended to respect an HTA in the order
      of 180/105 mm HG except under certain conditions (acute lung oedema, aortic
      dissection, infarction acute myocardial) that requires a rapid stabilization of
      blood pressure. Thrombolysis using alteplase (rt-PA) is called in neurovasalar
      units in case of stroke seen before the 3rd hour and in the absence of
      contraindications. Anticoagulants are shown in prevention of recurrence of stroke
      in the embolic heart disease with high risk of recidivism, in the carotid
      stenosis or vertebral basilar tight with hemodynamic impact downstream and in the
      extensive thrombosis. The treatment antiplatelet medication is indicated in other
      cases. The screening and the control of risk factors for vascular constitute an
      effective weapon for primary prevention. The rehabilitation motor, speech and
      language and occupational therapy can improve rehabilitation for patients. The
      prognosis vital and functional depend partly in the early and appropriate
      management of stroke and also in increasing of education and awareness of
      population and health care personnel and especially on the diffusion of the means
      of prevention primary

PMID- 19102114
TI  - [Perforation and haemorrhage duodenal bulbar ulcers in a child: a case report].
AB  - A perforation rarely reveals a primary duodenal ulcer. The occurring of digestive
      haemorrhage in post operative followings evokes spontaneously a stress ulcer. We
      report an observation of a child who presented on fourth day delay after
      operation an ulcer of the anterior duodenal bulbar face and a haemorrhage of the
      posterior bulbar face. A 7-year-old girl with no particular pathological
      antecedent was admitted for abdominal pain, bile vomiting and constipation
      evolving since 6 days. Clinical examination revealed a general state thickening,
      an infectious syndrome, a meteoric and general abdominal sensitivity. The
      abdominal radiography without preparation showed a pneumoperitoneum. The surgical
      exploration discovered a perforated ulcer on the bulbar anterior face. A simple
      closure associated with omental patch was performed. Four days after operation,
      she presented an abundant digestive haemorrhage with shock. The resuscitation did
      not improve the patient's general state. The upper digestive endoscopy revealed a
      haemorrhage of the posterior bulbar face. An adrenalin injection stopped the
      bleeding. The treatment by neutron pump inhibitors and an eradicating treatment
      of Helicobacter pylori permitted the healing of the ulcers. The occurring of
      digestive haemorrhage in the followings of surgical intervention for perforated
      ulcer involves an upper digestive endoscopy. This examination can reveal
      misdiagnosed ulcer during the surgical exploration and permits to perform a
      haemostatic act.

PMID- 19102115
TI  - [Management of exocrin pancreatic tumor. About 129 cases].
AB  - Management of exocrine pancreatic tumors is very difficult: Their impact is in
      upsurge and their diagnosis is very often made to an advanced stage that only
      allows the therapeutic palliative. To value the management of these tumors to the
      surgical clinic of Aristide Le Dantec hospital, authors achieved a retrospective
      survey on 8years (October 1994 to October 2002). Hundred twenty nine (129) cases
      of exocrine pancreatic tumors had been counted. It was about 71 men and 58 women
      of middle age of 56, 96 years. The length of middle evolution of the illness was
      of 8 months. The most frequent sign was jaundice, recovered at 80.9% of patients.
      Followed the thinning (79%), the pain (69%), the digestive stenosis (35%).
      Ultrasonography, scanner and x-ray of lungs permitted to make the diagnosis and
      the balance of extension. A laparoscopy had been made at 13 patients. A clinic
      and radiological classification had been used to distribute the tumors in 3
      stages. At 46 patients in III stage, a therapeutic abstention had been decided.
      Patients to the II stage (n=77) had benefitted a palliative surgical treatment.
      It was about 74 biliary and digestive shunt and 3 alcoholic splanchnicectomy. The
      6 patient to the I stage had benefitted a surgical resection. The middle
      hospitalization length was of 10.75 days. The rate of morbidity was 45.78%.
      Mortality was 29%. The median survival was of 3.6 months. The palliative surgical
      treatment had again indications facing these obstructive and locally advanced
      tumors. But the salute will come from the precocious diagnosis of these tumors to
      hope for a curative gesture.

PMID- 19102116
TI  - [Hand washing at Fann hospital: investigation among health workers].
AB  - INTRODUCTION: Handwashing is usually neglected in hospital settings. The
      objective of this study was to draw attention of health workers in Fann hospital
      as part of the prevention of hospital-acquired infections. MATERIALS AND METHODS:
      This study was carried out prospectively from April 26h to May 25th. An anonymous
      questionnaire was administered by 20 formed investigators to health workers,
      along with an inventory of available resources for hand washing in the study site
      allowing to collect the data by interview. RESULTS: A total of 256 health workers
      were investigated. The mean age was 35.3 +/- 9.4 years [range = 20-71] with a sex
      ratio of 0.62. As for the education level, the secondary and university
      predominated. The concept of Manu carrying was ignored by 59.3% of the personnel.
      This proportion was higher among people with low education level. Possibility of
      resident and transitional floras in the hand was ignored by most of the
      investigated personnel. The hand washing technique to be applied while putting
      vesicle probe was ignored by 59% of the personnel, and 34% declared using hand
      towel to dry hands. Half of the personnel ignored that bread soap was not
      recommended. The availability of hydro alcoholic solutions was variable according
      to the hospital wards. The lavabo/bed ratio was 1/7 and was unacceptable.
      CONCLUSION: In Fann hospital, the importance and the techniques of hand washing
      are not well known, that's why a training of the hospital's Personnel and an
      improvement of resources for handwashing are necessary for a good hospital's
      hygiene.

PMID- 19102117
TI  - [Nephrotic syndrom with focal and segmental glomerulosclerosis in Dakar:
      epidemiological and clinicopathological characteristics (about 134 cases)].
AB  - Focal and segmental glomerulosclerosis (FSGS) is common and non-specific patterns
      of glomerular injury encountered in human renal biopsies. Cortico-resistant
      nephrotic syndrome is the main manifestation. We report epidemiological, clinical
      and pathological aspects of FSGS in Dakar. We report the results of a
      retrospective study about focal segmental glomerulosclerosis (FSGS) identified
      from 258 kidney biopsies performed in the medical clinic 1 of A. Le Dantec
      hospital from January 1993 to December 2003. FSG is found in 134 cases (52%),
      membranous glomerulonephritis in 32 cases (12,4%), minimal change disease in 20
      cases (7.7%). Ninety eigths files were exploitable. FSGS has male gender
      predominance with a sex ratio of 3. Median age of patients is 28 years (15 and 79
      years). Symptomatology is dominated by oedema in 86 cases (87,7%), hypertension
      in 12 cases (12.2%), hematuria in 5 cases (5.1%), nephrotic proteinuria in 65
      cases (66,3%) and no nephrotic proteinuria in 33 cases (33.6%), renal failure in
      25 cases (25%)and leucocyturia in 18 cases (18%). FSGS involving more than 50% of
      glomeruli is encountered in 41 cases (42%), severe interstitial fibrosis is
      associated in 26 cases. Different pathological aspects are: classical FSGS in 88
      cases (88.7%), FSGS " collapsing" in 7 cases (7.1%), FSG "tip-lesion" in one
      case, FSGS associated to membranous glomerulosclerosis in 2 cases and to diabetic
      glomerulosclerosis in one case. FSGS is primitive in 88 cases (89,8%) and
      secondary in 10 cases (10.2%). FSGS is the most common primitive glomerulopathy
      in Dakar. Nephrotic syndrome is the main manifestation of this disease.
      Collapsing FSGS is not correlated with the HIV Infection.

PMID- 19102118
TI  - [Toxicological study of emissions resulting from a diesel and a gazoline engine
      using an organotypic culture of lung slice].
AB  - INTRODUCTION: Many studies were carried out in vivo and/or in vitro for better
      understanding toxic effects of exhausts or particles emitted by Diesel vehicles.
      Few studies were interested in Gazoline engines when progress of metrology made
      it possible to highlight the presence of small particles with a strong capacity
      of penetration within pulmonary tissue. The aim of this study is to compare the
      toxic impact of the emissions of Diesel and Gasoline engines of recent
      technology. MATERIALS AND METHODS: Biological material was constituted by an
      organotypic rat lung precision slice. It was exposed to a continuous flow
      exhausts thanks to a preparation and dilutions system of these emissions placed
      on the line of exhaust. A measurement of the biological markers involved in the
      process of the lung tissue reaction to the air-contaminants was carried out.
      RESULTS: With Diesel exhausts, the results showed a stability of the rate of ATP
      and an increase in enzymatic activities of the antioxydant system (GPx and
      catalase). Gazoline emissions, as for them, were responsible for a cytotoxic
      attack of the pulmonary tissue defined by a reduction in the rate of ATP as well
      as a deterioration of the system of detoxication with reduction in the
      antioxydant enzymatic activities. CONCLUSION: These results show that
      toxicological profiles obtained with this system of exposure depends on the
      engine technology used, highlighting thus the specific response of the model in
      relation with the type of atmospheres which it is exposed.

PMID- 19102119
TI  - [Enhancing the anthelminthic activity roots of Annona sengalensis].
AB  - INTRODUCTION: Annona senegalensis is a plant largely used in traditional medicine
      in Africa. The roots showed an antiparsitic activity. The purpose of this work is
      to determine through bioassay on Rhabditis pseudoelongata the activity of the
      roots of Annona senegalensis and characterise if any substances responsible for
      this activity. MATERIAL AND METHODS: The vegetable material consists of roots of
      Annona senegalensis collected in Casamance at 1999. The tests of activity are
      carried out on Rhabditis pseudoelongata, stock L. Lamy, Institut Pasteur, Paris.
      Powder of roots (1070 g) was extracted with methanol. From this rough extract, we
      carried out two extractions with the dichloromethane of which one after passages
      in alkaline and acid medium. Various extracts were subjected to a chromatography
      on column of silica gel or from alumina gel; some compounds were isolated by high
      performance liquid chromatography . The identification of compounds was deed
      using spectrometric techniques (mass, Ultraviolet, Infrared) and nuclear magnetic
      resonance. The tests of activity related to three extracts and seven molecules
      isolated from the roots. The percentage of dead worm is determined after two
      hours of contact with demineralised water containing the sample to be tested.
      RESULTS: The neutral extract chloromethylenic showed an important activity on
      Rhabditis pseudoelongata. Five acetogenines were insulated starting from this
      extract chloromethylenic (gigantetronenine, squamocine, glaucanisine,
      glaucanetine, goniothalamicine) and two alkaloids starting from the alkaline
      extract chloromethylenic (liriodenine and noroliveroline). The tests on Rhabditis
      pseudoelongata of these compounds showed an activity of the squamocine with a
      IC50 of 0.1 microg/ml and IC90 0.3 microg/ ml more powerful than that of the
      levamisole, reference substance (IC50 of 0.8 microg/ml and IC90 13 microg/ml).
      CONCLUSION: The study of the biological activity of the roots of Annona
      senegalensis made it possible to determine the anthelminthic activity of the
      extract chloromethylenic from where the squamocine was isolated. The presence of
      this molecule could explain the anthelminthic activity of this plant.

PMID- 19102120
TI  - [Vascular aphasias: clinical, epidemiologicaland evolutionary aspects].
AB  - INTRODUCTION: Aphasias constitute an acquired disorder of the language.
      Aetiologies are dominated by stroke. The aim of this study was to describe the
      clinical, epidemiological and evolutionary aspects of the vascular aphasias.
      MATERIALS AND METHODS: We conducted from August 2003 to May 2005 a descriptive
      cross-sectional study at the Neurology department in Dakar. This study concerned
      all patients admitted at the Neurology department for stroke confirmed by the
      cerebral tom densitometry. All patients were subjected to an examination of the
      language allowing to confirm the diagnosis of aphasia and to determine the type.
      The follow-up was monthly during one year. RESULTS: 55 cases of aphasia were
      reported on 170 cases of stroke (frequency: 32.35%). Our patients were all right
      handed. Mean age was 56.8 (28 to 86 years) with a sex-ratio of 0.61.76.36% of the
      patients could neither read nor to write. Only two made higher studies. The
      nature of stroke was ischemic in 73.7% and hemorrhagic in 26.3%. The aphasias
      with expressive language impairment were observed in 96.4% against 3.6% of the
      cases for aphasias with comprehensive language impairment. After one year of
      evolution, a regression of the disorders was observed only in 9 cases, and the
      regression was partial in 25 cases. The evolution of the aphasia was correlated
      with that of the motor deficit. Age, low educational level, ischemic stroke
      constitute factors of bad prognosis. CONCLUSION: Vascular aphasias are frequent
      and of reserved prognosis. It disturbs social professional and family
      reintegration.

PMID- 19102121
TI  - [Evaluation of an immunoassay for calcitonin].
AB  - INTRODUCTION: The calcitonin is the most specific and the most sensitive marker
      of medullary thyroid carcinoma (MTC) both for screening and postoperative follow
      up of the patients. Its measurement is made either remotely , or after
      stimulation of pentagastrin secretion which the answer is amplified at the
      carrier of CMT. The aim of this study was to estimate a chimioluminescent method
      by comparing it with an immunoradiological method, manual, used as reference.
      Correlation study was done. MATERIALS AND METHODS: Two hundred and sixty three
      serums (263) were tested among which 64 resulting of healthy subjects and 199
      resulting of patients affected) by medullary thyroid carcinoma. Statistical
      analysis of results was made by a study of correlation with the software
      OriginLab version 7.0. The manual technique used as reference method is
      radioimmunological (Elsa hCT, international Cisbio, Gif on Yvette, France). It
      was compared with a chimioluminescent technique (Nichols Advantage, Nichols
      Institute Diagnostics, CA, the USA). RESULTS: The coefficients of correlation
      obtained between both tests were: r = 0.76 (exactness study), r = 0.91 (after
      stimulation), r = 0.95 and 0.79 (staged samples), r = 0.99 (M TC patients).
      CONCLUSIONS: Both techniques correlate strictly and significantly. The
      correlation coefficients we obtained show us that Nichols Advantage Calcitonin is
      completely reliable and sensitive for the measurement of the hCT in the follow-up
      of the CMT.

PMID- 19102122
TI  - [Study of the contents in fat, in protein and in vitamin D of powdered milk
      varieties sold in Dakar].
AB  - INTRODUCTION: The powdered milk is a much appreciated food in Senegal. However no
      particular control is realized by authorities on the various marks of milk
      imported before their marketing. In the concern to protect the health of the
      consumers, but especially in front of the very big variety of the sources of
      supply in this product we determined the contents in fat, in protein and in
      vitamin D main variety show of marketed powdered milk Dakar. MATERIAL AND
      METHODS: Chemical methods were operated to determine the fat contents and in
      proteins. The liquid chromatography in high performance was used to identify and
      measure the vitamin D. RESULTS: The obtained results profits showed that all the
      studied samples of milk had contents in fat included between 25 and 31 g %, those
      in proteins were included between 23 and 25 g %. As regards the dosage of the
      vitamin D, a single sample had content weaker than that mentioned on the
      packaging by the manufacturer. CONCLUSION: The results of this study allowed to
      notice most of the variety varieties of powdered milk marketed in Dakar were in
      accordance with the standards established for this food and are consequently good
      quality.

PMID- 19102123
TI  - Treatment of tinnitus with a customized, dynamic acoustic neural stimulus:
      clinical outcomes in general private practice.
AB  - OBJECTIVES: We evaluate the relative effectiveness of a newly available tinnitus
      treatment approach for different categories of patients in general private
      practice. METHODS: This was a cohort study, sponsored by Neuromonics, involving
      the first 470 patients to undertake the Neuromonics Tinnitus Treatment in 7
      Neuromonics tinnitus clinics. All patients were provided with a dynamic acoustic
      neural stimulus, customized to each patient's audiometric profile, for daily use
      as part of a structured rehabilitation program. Tinnitus disturbance was assessed
      before, during, and after treatment with the Tinnitus Reaction Questionnaire.
      RESULTS: The outcomes displayed a relation with patients' suitability according
      to predefined criteria: among the most suitable patients (tier 1 cohort), 92%
      exceeded the threshold for success (defined as a reduction in tinnitus-related
      disturbance of at least 40%), and the mean improvement in tinnitus disturbance
      was 72%; the discontinuance rate was 4%. For other suitability categories, the
      success rates and mean improvements were somewhat lower, and the discontinuance
      rates higher (tier 2: 60%, 49%, and 16%, respectively; tier 3: 39%, 32%, and 17%,
      respectively). CONCLUSIONS: The results showed that the treatment is effective
      for suitable patients in the private practice setting, and they provide health
      care professionals with guidance as to what patients might expect from treatment,
      depending on their degree of suitability.

PMID- 19102124
TI  - Vestibular evoked periocular potentials in Meniere's disease after glycerol
      testing.
AB  - OBJECTIVES: The present investigation was specifically designed to evaluate the
      clinical application of vestibular evoked periocular potentials (VEPPs) in the
      diagnosis of endolymphatic hydrops. METHODS: We compared the results of the
      traditional pure tone audiometry glycerol test with those of the vestibular
      evoked myogenic potential (VEMP) glycerol test and the VEPP glycerol test in 22
      patients affected by unilateral endolymphatic hydrops. RESULTS: Some patients had
      positive depletive tests with both VEMPs and VEPPs, and other patients had
      positive tests with either VEMPs or VEPPs. CONCLUSIONS: Our outcomes confirmed
      that vestibular evoked potentials represent a useful additional diagnostic tool
      in the diagnosis of endolymphatic hydrops. The role of VEPPs in this particular
      issue was not inferior to that of VEMPs. The outcomes also suggested that not
      only the saccule, but also the utriculus, may be involved in the genesis of
      VEPPs.

PMID- 19102125
TI  - Nijmegen results with application of a bone-anchored hearing aid in children:
      simplified surgical technique.
AB  - OBJECTIVES: A retrospective analysis was performed to evaluate the clinical
      outcome of percutaneous bone-anchored hearing aid (BAHA) application in children
      with the outcome measures of fixture loss and skin reactions. METHODS: An
      analysis was done of 93 of the 101 children 16 years of age or younger who
      underwent the simplified Nijmegen surgical technique between January 1994 and
      July 2007. RESULTS: Twenty-one of 129 fixtures (16.3%) were lost or removed. In
      12 cases, osseointegration failed. The majority of the fixture losses (86%)
      occurred within 1 year after surgery. No differences were found between 3 age
      groups or between fixture lengths (seven 3-mm implants versus fourteen 4-mm
      implants). The BAHA fixtures were less stable in children than in adults. In 8
      cases, Holgers grade 4 skin reactions were noted at an average (+/-SD) of 5.5 +/-
      4.7 months after surgery, ie, significantly sooner than the milder reactions (p =
      0.001). In 28 cases (22%), skin reactions of Holgers grades 2 to 4 were observed.
      Revision surgery to reduce subcutaneous scar tissue was necessary in 22 implants
      (17%). CONCLUSIONS: Fixture loss was more frequent in children than in adults.
      The age of the child and the length of the fixture did not appear to influence
      fixture stability. Children should undergo frequent checkups at the outpatient
      clinic.

PMID- 19102126
TI  - Adjustable tongue advancement for obstructive sleep apnea: a pilot study.
AB  - OBJECTIVES: Surgical treatment of obstructive sleep apnea (OSA) caused by
      hypopharyngeal collapse of the upper airway can be considered in patients who are
      intolerant to continuous positive airway pressure (CPAP). The present procedures
      addressing the hypopharynx are invasive and have substantial morbidity and
      limited efficacy. METHODS: Ten patients (mean age, 44 years) with moderate to
      severe OSA, ie, an apnea-hypopnea index (AHI) between 15 and 50, with CPAP
      intolerance were included in a prospective, nonrandomized, multicenter study to
      evaluate the feasibility, safety, and efficacy of a novel tongue advancement
      procedure. The procedure consists of the implantation of a tissue anchor in the
      tongue base and an adjustment spool at the mandible. Titration of this tissue
      anchor results in advancement of the tongue and a patent upper airway. RESULTS:
      The mean AHI decreased from 22.8 at baseline to 11.8 at the 6-month follow-up (p
      = 0.007). The Epworth Sleepiness Scale score decreased from 11.4 at baseline to
      7.7 at the 6-month follow-up (p = 0.094), and the snoring score decreased from
      7.5 at baseline to 3.9 at the 6-month follow-up (p = 0.005). Four technical
      adverse events were noted, and 1 clinical adverse event occurred. CONCLUSIONS:
      Adjustable tongue advancement is a feasible and relatively safe way to reduce the
      AHI and snoring in selected patients with moderate to severe OSA and CPAP
      intolerance. Technical improvements and refinements to the procedure are ongoing.

PMID- 19102127
TI  - Cystic lymphatic malformation of the middle ear.
AB  - OBJECTIVES: We review the clinical, radiologic, and histopathologic features of
      cystic lymphangioma of the middle ear, and discuss the developmental etiology and
      management of such a lesion. METHODS: We present an unusual location for the
      development of a cystic lymphangioma with emphasis on etiology, clinical
      implications, and current treatment. RESULTS: A 10-year-old girl presented with a
      mass involving the medial surface of the right tympanic membrane. T2-weighted
      magnetic resonance imaging demonstrated a hyperintense lesion in the anterior
      superior middle ear cavity without evidence of vascular abnormalities.
      CONCLUSIONS: To our knowledge, this is the only report of lymphangioma involving
      the middle ear represented in the English-language literature. Such a lesion has
      been demonstrated to arise from abnormalities in growth factors that contribute
      to the tightly regulated process of lymphangiogenesis. Lymphatic malformations
      can be diagnosed presumptively by virtue of magnetic resonance imaging in
      combination with a detailed physical examination. The treatment of choice for
      lymphangiomas located in the middle ear is surgical excision. Definitive
      diagnosis of the lesion is then made by identifying specific histopathologic
      characteristics. Although rare and histologically benign, middle ear
      lymphangiomas may produce significant patient discomfort and ultimately a
      conductive hearing loss. Therefore, these lesions warrant early recognition and
      treatment.

PMID- 19102129
TI  - Performance of an automated, remote system to detect vocal fold paralysis.
AB  - OBJECTIVES: The aim of this project was to evaluate the diagnostic accuracy of an
      automated, remote system for correctly identifying vocal fold paralysis. METHODS:
      Consecutive patients presenting for vocal analysis at the Beaumont Hospital Voice
      Clinic were enrolled in this prospective, blinded study. Control patients were
      enlisted from routine otolaryngology clinics. All patients were assessed by
      standard history, clinical examination, and flexible laryngoscopy or
      videostroboscopy. The subjects were blindly assessed by remote voice analysis.
      Sustained phonation was recorded over a standard telephone network. Each
      recording was subjected to automated, remote analysis of extracted features,
      including measures of pitch perturbation, amplitude perturbation, and harmonics
      to-noise ratio. The presence or absence of a vocal fold paralysis as determined
      by the automated classifier was recorded and correlated with clinical findings.
      RESULTS: Seventy-eight consecutive patients were enrolled in the study. The
      automated speech analysis system demonstrated 92% sensitivity and 75% specificity
      for detecting vocal fold paralysis. CONCLUSIONS: This pilot study, assessing an
      automated system that analyzes audiological data remotely over the standard
      telephone network, suggests that with further "training" it may become a
      reliable, simple, and convenient means for screening patients for voice
      disorders.

PMID- 19102128
TI  - Unique transgenic animal model for hereditary hearing loss.
AB  - OBJECTIVES: This study capitalizes on the unique molecular and developmental
      similarities between the auditory organs of Drosophila and mammals, to
      investigate genes implicated in human syndromic and nonsyndromic hearing loss in
      a genetically tractable experimental animal model, the fruit fly Drosophila.
      METHODS: The Drosophila counterparts of 3 human deafness genes (DIAPH1/DFNA1,
      ESPN/DFNB36, and TMHS/DF-NB67) were identified by sequence similarity. An
      electrophysiological assay was used to record sound-evoked potentials in response
      to an acoustic stimulus, the Drosophila courtship song. RESULTS: Flies with
      mutations affecting the diaphanous,forked, and CG12026/TMHS genes displayed
      significant reductions in the amplitude of sound-evoked potentials compared to
      wild-type flies (p < 0.05 to p < 0.005). The mean responses were reduced from
      approximately 500 to 600 microV in wild-type flies to approximately 100 to 300
      microV in most mutant flies. CONCLUSIONS: The identification of significant
      auditory dysfunction in Drosophila orthologs of human deafness genes will
      facilitate exploration of the molecular biochemistry of auditory
      mechanosensation. This may eventually allow for novel diagnostic and therapeutic
      approaches to human hereditary hearing loss.

PMID- 19102130
TI  - Computerized scoring system for the diagnosis of foreign body aspiration in
      children.
AB  - OBJECTIVES: Foreign body aspiration (FBA) is a life-threatening event in
      children. The gold standard for diagnosis is bronchoscopy, but there is no
      consensus regarding indications for the procedure. The aim of this study was to
      formulate a predictive model for assessing the probability of FBA in suspected
      cases as an aid in the decision to perform diagnostic bronchoscopy. METHODS: The
      files of 150 patients who underwent bronchoscopy for suspected FBA at our center
      between 1996 and 2004 were reviewed for medical history, physical examination,
      and radiologic studies. The findings were analyzed by logistic regression.
      RESULTS: Using the file data, we formulated a predictive model wherein each
      parameter received a numeric coefficient representing its significance in
      evaluating suspected FBA. The most significant parameters were age 10 to 24
      months, foreign body in the child's mouth and severe respiratory complaints
      during the choking episode, hypoxemia, dyspnea or stridor following the acute
      event, unilateral signs on lung auscultation, abnormal tracheal radiogram,
      unilateral infiltrate or atelectasis, and local hyperinflation or obstructive
      emphysema on chest radiogram. CONCLUSIONS: In our predictive model, every case of
      suspected FBA can be assigned a score based on the specific parameters present,
      which is then entered into a probability formula to determine the likelihood of a
      positive diagnosis. This model may serve as a useful tool for deciding on the use
      of bronchoscopy in all children with suspected FBA.

PMID- 19102131
TI  - Development of mucosal thickening after radiotherapy in contralateral sinuses of
      patients with nasal cavity and/or paranasal sinus carcinoma.
AB  - OBJECTIVES: The aim of this study was to investigate the development of
      radiotherapy (RT)-induced mucosal thickening (MT) of the contralateral sinuses in
      patients with nasal cavity and/or paranasal sinus carcinoma. METHODS: We
      retrospectively reviewed the medical records and the initial and follow-up
      computed tomography (CT) scans of 37 patients with RT and 10 controls without RT.
      The CT scans were scored on the Lund-Mackay (LM) staging system. RESULTS: Fifteen
      of the 37 patients had MT before RT, and the mean LM score was 0.68. The MT
      incidence significantly increased, to 72.9% (p = 0.009), and the LM score
      significantly increased, to 2.84 (p < 0.001), by 3 months after RT, after which
      the LM score decreased gradually to 1.73 at 36 months after RT. Four of the 10
      controls had MT before treatment, and their mean LM score was 0.7. Their MT
      incidence and LM score had not changed significantly at 3 months after treatment.
      The pretreatment LM scores of the patient group and the control group were not
      significantly different, but their posttreatment LM scores were significantly
      different at the 3-month follow-up (p = 0.033). CONCLUSIONS: Use of RT in
      patients with nasal cavity and/or paranasal sinus carcinoma may cause a
      significant increase in the incidence of MT and in the LM scores in all sites of
      the paranasal sinuses by 3 months after RT, after which the LM score decreases
      gradually.

PMID- 19102132
TI  - Postoperative monitoring of esophageal pressure in patients with obstructive
      sleep apnea-hypopnea syndrome who have undergone tonsillectomy with
      uvulopalatopharyngoplasty.
AB  - OBJECTIVES: To realize better postoperative management in patients with
      obstructive sleep apnea-hypopnea syndrome (OSAHS), we elucidated the need for the
      postoperative monitoring of esophageal pressure (Pes). METHODS: A prospective
      randomized controlled study was performed. Adult patients with OSAHS were divided
      into 2 groups: those administered autoadjusted continuous positive airway
      pressure (CPAP) before, on, and after the first postoperative night (CPAP group)
      and those not administered CPAP before or after the surgery (non-CPAP group).
      Tonsillectomy with uvulopalatopharyngoplasty (UPPP) under general anesthesia was
      performed on all of the patients. On the first postoperative night, continuous
      overnight monitoring of Pes and oxygen saturation level was carried out
      simultaneously with oxygen supplementation in both groups in the patient's room
      in the general ward. RESULTS: The CPAP group showed a significantly improved mean
      inspiratory maximal end-apneic Pes swing on the first postoperative night as
      compared with the non-CPAP group, although there was no significant difference in
      oxygen desaturation index on the first postoperative night between the 2 groups.
      CONCLUSIONS: Continuous Pes monitoring and CPAP administration were beneficial in
      the detection and minimization of respiratory disturbances in patients with OSAHS
      who underwent tonsillectomy with UPPP under general anesthesia.

PMID- 19102133
TI  - Is there a need for positron emission tomography imaging to stage the N0 neck in
      T1-T2 squamous cell carcinoma of the oral cavity or oropharynx?
AB  - OBJECTIVES: We assess whether negative findings on computed tomography (CT),
      magnetic resonance imaging (MRI), and/or 18F-fluorodeoxyglucose positron emission
      tomography (18FDG-PET) may contribute to the decision-making process of elective
      neck dissection (eND) in patients with squamous cell carcinoma of the oral cavity
      or the oropharynx (oSCC) staged cT1-T2 cN0 cM0. METHODS: We interpreted CT, MRI,
      and 18FDG-PET images separately, after combining the data of CT with those of
      18FDG-PET and the data of MRI with those of 18FDG-PET. Each set of results was
      then compared with the histopathologic results of ipsilateral or bilateral eND in
      a prospective, blinded study. RESULTS: The histopathologic examination of 594
      lymph nodes revealed 4 metastases less than 4 mm in diameter and 3
      micrometastases (less than 2 mm) in 6 of 17 patients. On CT, MRI, and 18FDG-PET,
      respectively, 5, 5, and 0 cases were true-malignant (true positives) and 4, 10,
      and 1 cases were false-malignant (false positives). The accuracy was not enhanced
      by fusing CT with 18FDG-PET or MRI with 18FDG-PET. CONCLUSIONS: The detectability
      threshold of occult metastases appears to be below the spatial and contrast
      resolution of CT, MRI, and 18FDG-PET. The decision for eND in patients with cT1
      T2 cN0 cM0 oSCC cannot be based upon cross-sectional imaging at the resolutions
      currently available.

PMID- 19102134
TI  - Cod liver oil, vitamin A toxicity, frequent respiratory infections, and the
      vitamin D deficiency epidemic.

PMID- 19102135
TI  - Alternate measures of replacement rates for social security benefits and
      retirement income.
AB  - Discussions of retirement planning and Social Security policy often focus on
      replacement rates, which represent retirement income or Social Security benefits
      relative to preretirement earnings. Replacement rates are a rule of thumb
      designed to simplify the process of smoothing consumption over individuals'
      lifetimes. Despite their widespread use, however, there is no common means of
      measuring replacement rates. Various measures of preretirement earnings mean that
      the denominators used in replacement rate calculations are often inconsistent and
      can lead to confusion. Whether a given replacement rate represents an adequate
      retirement income depends on whether the denominator in the replacement rate
      calculation is an appropriate measure of preretirement earnings. This article
      illustrates replacement rates using four measures of preretirement earnings:
      final earnings; the constant income payable from the present value (PV) of
      lifetime earnings (PV payment); the wage-indexed average of all earnings prior to
      claiming Social Security benefits; and the inflation-adjusted average of all
      earnings prior to claiming Social Security benefits (consumer price index (CPI)
      average). The article then measures replacement rates against a sample of the
      Social Security beneficiary population using the Social Security Administration's
      Modeling Income in the Near Term (MINT) microsimulation model. Replacement rates
      are shown based on Social Security benefits alone, to indicate the adequacy of
      the current benefit structure, as well as on total retirement income including
      defined benefit pensions and financial assets, to indicate total preparedness for
      retirement. The results show that replacement rates can vary considerably based
      on the definition of preretirement earnings used and whether replacement rates
      are measured on an individual or a shared basis. For current new retirees,
      replacement rates based on all sources of retirement income seem strong by most
      measures and are projected to remain so as these individuals age. For new
      retirees in 2040, replacement rates are projected to be lower, though still
      adequate on average based on most common benchmarks.

PMID- 19102136
TI  - Social Security beneficiaries affected by the Windfall Elimination Provision in
      2006.
AB  - The Windfall Elimination Provision (WEP) is an alternative method of computing
      benefits for some workers who receive a pension based on work not covered by
      Social Security. The WEP computation results in a lower benefit than the worker
      would receive under the regular computation method. This article provides a brief
      legislative history, describes the WEP computation and applicability, and
      presents statistical data about beneficiaries affected by the WEP. The
      statistical data show that, as of the end of December 2006: About 970,000
      beneficiaries, mainly retired workers, were affected by the WEP, and the WEP
      affected the benefits of almost 3 percent of all retired workers. Almost half of
      the retired workers affected by the WEP received a federal pension, and another
      36 percent received either a state or local pension. Sixty-five percent of both
      retired and disabled workers affected by the WEP were men.

PMID- 19102137
TI  - An overview of the Railroad Retirement program.
AB  - In the 1930s, amidst concern about the ability of existing pension programs to
      provide former railroad workers with adequate assistance in old age, Congress
      established a national Railroad Retirement system. This system is primarily
      administered by the Railroad Retirement Board (RRB), which is an independent
      federal agency charged with providing benefits to eligible employees of the
      railroad industry and their families. Today, the Railroad Retirement program is
      closely tied to the far better-known Social Security program, and although the
      Railroad Retirement program and Social Security share a number of common
      elements, key differences also exist between the two in areas such as funding and
      benefit structure. This article aims to increase awareness and understanding of
      the Railroad Retirement program and its relationship with Social Security by
      examining the parallel development of these two retirement programs while
      illuminating areas where the two diverge. The history of the Railroad Retirement
      program, the benefits provided by the program, and RRB's financial operations are
      reviewed, using elements of the Social Security system as points of reference.

PMID- 19102138
TI  - The Canadian safety net for the elderly.
AB  - Recently various analysts have called attention to the apparent success of the
      Canadian social assistance system in reducing poverty among the elderly and have
      suggested that there may be lessons to be drawn from the Canadian experience that
      are relevant to the evolution of the U.S. Supplemental Security Income (SSI)
      program. This article profiles the Canadian system, compares the system to the
      U.S. SSI program, reviews the consequences for elderly poverty rates, assesses
      system costs, and then comments on pertinence of the Canadian experience to SSI
      policy. The Canadian minimum income guarantee for the elderly is substantially
      more generous than what is provided by the United States, but it is misleading to
      claim that the Canadian system costs only "slightly more" than the U.S. program.
      Such a judgment overlooks a key and costly part of the Canadian system, the Old
      Age Security demogrant. We estimate the total costs to Canada of providing income
      support for elderly persons receiving a Guaranteed Income Supplement (GIS) in
      2004 to be approximately C$13.3 billion (roughly US $11.1 billion), slightly more
      than 1 percent of gross domestic product (GDP) and almost fourteen times the U.S.
      allocation for SSI and food stamps for elderly SSI recipients. The significance
      of this commitment is underscored when it is recognized that in 2004 Canadian GDP
      per capita was just 80 percent of the U.S. level. The Canadian example suggests
      U.S. policymakers consider better integration of SSI with basic Social Security
      benefits, experimenting with alternatives to restricting SSI eligibility to
      individuals with very few assets, and reducing barriers to program access.

PMID- 19102139
TI  - Chile's next generation pension reform.

PMID- 19102140
TI  - [Therapeutic status of clavicular fracture].

PMID- 19102141
TI  - [The randomized controlled trial of the treatment for clavicular fracture by
      rotatory manual reduction with forceps holder and retrograde percutaneous pinning
      transfixation].
AB  - OBJECTIVE: To study the curative effect and safety of rotatory manual reduction
      with forceps holder and retrograde percutaneous pinning transfixation in treating
      clavicular fracture. METHODS: All 201 cases of clavicular fractures were randomly
      divided into treatment group (101 cases) and control group (100 cases). The
      treatment group was treated by rotatory manual reduction with forceps holder and
      retrograde percutaneous pinning transfixation. The control group was treated by
      open reduction and internal fixation with Kirschner pin. All cases were followed
      up for 4 to 21 months (mean 10.6 months). SPSS was used to analyze clinic healing
      time of fracture and shoulder-joint function in both two groups. RESULTS: After
      operation, 101 cases of treatment group achieved union of fracture and the
      clinical healing time was 28 to 49 days (mean 34.5+/-2.7 days). In control
      group,there were 4 cases with nonunion of fracture,the other 96 cases were
      union,the clinical healing time was 36 to 92 days (mean 55.3+/-4.8 days). The
      excellent and good rate of shoulder-joint function was 100% in treatment group
      and 83% in control group. By t-test and chi2-test, there was significant
      difference between the two groups in curative effect (P<0.05). CONCLUSION:
      Rotatory manual reduction with forceps holder and retrograde pinning
      transfixation can be used in various kinds of clavicular shaft fracture, with
      many virtues such as easy operation, reliable fixation, short union time of
      fracture, good functional recovery of shoulder-joint and no incision scar
      affecting appearance.

PMID- 19102142
TI  - [Clinical controlled trial on the treatment of comminuted clavicular fracture
      with acromioclavicular external fixator and clavicle anatomic DCP internal
      fixation].
AB  - OBJECTIVE: To explore the different therapeutic effects of comminuted clavicular
      fracture with acromioclavicular external fixtatior and DCP internal fixation.
      METHODS: There were 768 cases of comminuted clavicular fracture involved in the
      study. Among them, 528 patients (321 male and 207 female, aged from 15 to 82
      years) treated with acromioclavicular external fixator, in which there were 165
      cases of three parts fracture and 363 cases of more than three parts fracture;
      240 patients (152 males and 88 females, aged from 17 to 64 years) treated with
      the internal fixation, in which there were 178 cases of three parts fracture and
      62 cases of more than three parts fracture. The time between injury and treatment
      was 1.3 days (range, 2 h to 8 days). The results were evaluated according to Neer
      scoring system. RESULTS: All the cases were followed up from 8 to 24 months. For
      treatment of fracture more than three parts, there was significant difference
      between acromioclavicular external fixation group and internal fixation group in
      nonunion rate (chi2=44.17, P<0.05) and in Neer scores (t=5.284, P<0.05).
      CONCLUSION: Treatment with DCP internal fixation which matching the AO principles
      can obtain anatomic reduction, firm fixation and early functional exercise;
      however, treatment with self-designed acromioclavicular external fixator is an
      ideal therapeutic method as it has, early union of the fracture and good
      functional outcome with seldom complications.

PMID- 19102143
TI  - [Surgical treatment of scapular neck fracture and floating shoulder].

PMID- 19102144
TI  - [Case-control studies of the treatment for the distal clavicle fracture by
      elastic band inclined "8" fixation].
AB  - OBJECTIVE: To compare the effects of the treatment for the distal clavicle
      fracture with two different methods. METHODS: There were 120 cases of the distal
      clavicle fractures involved in the study. Among them, 75 cases were treated by
      self-improved elastic band inclined "8" fixation (Manipulation group), 45 cases
      were treated by open reduction and internal fixation with clavicular hook plate
      (Operation group). RESULTS: There was statistically significant difference
      between manipulation group (6.71+/-2.35 weeks) and operation group (11.38+/-4.58
      weeks) in the time of fracture union (P<0.01); but, there was no statistically
      significant difference between manipulation group (100%) and operation group
      (97.8%) in the rate of fracture union (P>0.05). According to the evaluation of
      shoulder-joint function, 56, 14 and 5 cases obtained excellent, good and bad
      result respectively in manipulation group; 38, 5 and 2 cases obtained excellent,
      good and bad respectively in operation group. There was no statistically
      significant difference between manipulation group (93.3%) and operation group
      (95.5%) in the rate of excellent and good (P>0.05). CONCLUSION: Compared with
      open reduction and internal fixation with clavicular hook plate, treatment with
      self-improved elastic band inclined "8" fixation can shorten the union time of
      fracture and reduce therapeutic risks, so it is an economical, practical and safe
      method for the distal clavicle fracture.

PMID- 19102145
TI  - [Minimally invasive treatment of clavicular fracture by percutaneous pinning
      transfixation with homemade reduction].

PMID- 19102146
TI  - [Treatment of distal clavicle fracture and acromioclavicular joint dislocation
      with closed reduction and pinning].

PMID- 19102147
TI  - [A controlled clinical trial on the therapy of injured shoulder arthrochalasis by
      shoulder-elbow elastic band immobilization with functional exercise].
AB  - OBJECTIVE: To observe the therapeutic effects of shoulder-elbow elastic
      immobilization and functional exercise for injured shoulder arthrochalasis, and
      compare it with forearm-suspending immobilization and functional exercise
      therapy. METHODS: The patients with injured shoulder arthrochalasis were randomly
      divided into treatment group (38 cases) and control group (37 cases). Treatment
      group underwent the therapy of shoulder-elbow elastic band immobilization and
      functional exercise; control group was managed by forearm-suspending band
      immobilization and functional exercise therapy. RESULTS: In treatment group, 29
      (76.3%) cases recovered, 7 (18.4%) improved and 2 (5.3%) failed; in control
      group, 15 (40.5%) cases recovered, 15 (40.5%) cases improved and 7 (19.0%)
      failed. The differences between two groups were statistically significant
      (P<0.01). The AHI (acromio-humeral interval) ranged from 8 to 19 mm (11.9+/-5.1)
      in treatment group and 8 to 27 mm (14.2+/-5.4) in control group, and the
      difference was also statistically distinct (t=2.7525, P<0.01). CONCLUSION: The
      treatment with shoulder-elbow elastic band immobilization and exercise therapy
      for injured shoulder arthrochalasis is a safe and effective method.
      Immobilization with shoulder-elbow elastic band is better than forearm-suspending
      band for injured shoulder arthrochalasis.

PMID- 19102148
TI  - [Closed reduction and Kirschner wire internal fixation for the treatment of
      supracondylar fractures of the humerus in children].

PMID- 19102149
TI  - [Clinical observation of arthroscopic medial patellofemoral ligament overlap and
      lateral patellar retinaculum release in treatment of patellofemoral pain
      syndrome].
AB  - OBJECTIVE: To explore the therapeutic results of surgical treatment for
      patellofemoral pain syndrome. METHODS: One hundred patients (35 males and 65
      females, ranging from 50 to 70 years old with an average age of 63 years) with
      patellofemoral pain syndrome were randomly and equally divided into treatment
      group and control group. All patients underwent arthroscopic treatment. The
      patients in treatment group were treated with medial patellofemoral ligament
      overlap and lateral patellar retinaculum release, and the patients in control
      group were just treated with lateral patella retinaculum release which is a
      current widespread operation. RESULTS: All patients were followed-up with the
      mean time of 13 months, and were evaluated with HSS (hospital for special
      surgery) scoring system for the therapeutic effect. The mean score of treatment
      group (73.52+/-11.17) and control group (65.50+/-13.70) had statistical
      difference (P<0.05), which indicated that the therapeutic effect of medial
      patellofemoral ligament overlap and lateral patellar retinaculum release for
      treatment of patellofemoral pain syndrome was satisfying. CONCLUSION: Compared
      with lateral patellar retinaculum release, this procedure is superior in
      correcting the abnormal movement of patellofemoral joint, easily balancing
      patellofemoral joint space, effectively relieving the pain of anterior knee. No
      postoperative complications occur, such as intraarticular haematoma, necrosis and
      dislocation of patella and so on.

PMID- 19102150
TI  - [Treatment of anterior dislocation of shoulder joint with the method of hand
      pulling and knee-pushing].

PMID- 19102151
TI  - [A clinical trial on the treatment of compression fracture of osteoporotic
      vertebral body by self-made spinal expander].
AB  - OBJECTIVE: To observe the effects of self-made spinal expander in treatment of
      compression fracture of osteoporotic vertebral body. METHODS: Ninty-six patients
      were randomly divided into two groups, treatment group included 42 cases with 56
      centrums, 14 males and 28 females, aged from 50 to 69 years, and control group
      included 54 cases with 68 centrums, 19 males and 35 females, aged from 51 to 75
      years. All cases were examined by X-ray and CT. MRI was taken in 27 patients to
      make sure the diagnosis which was compression fracture of vertebral body due to
      osteoporosis. The degree of osteoporosis was judged by X-ray of L3 bone
      trabecula. Fifty-six centrums in treatment group were treated with self-made
      spinal expander and bone cement. Sixty-eight centrums in control group were
      treated with PVP. Compression rate and recovery rate of vertebral height, and
      leakage rate of bone cement were measured according to the Lee standard. RESULTS:
      (1) VAS between treatment group and control group had significant statistically
      difference (P<0.05). (2) In treatment group, compression rate of anterior and
      middle vertebal height were statistical difference before and after operation
      (P<0.05). In control group, the compression rate of pre-and post-operative
      vertebal height had no significant difference (P>0.05). (3) The recovery rate of
      kyphosis between treatment group (71.8%) and control group (37.8%) was
      significant statistically difference (P<0.05). (4) There was no cement leakage in
      the treatment group, however the leakage rate in control group was 47%. (5) The
      curative effect was assessed based on the standard of WHO. In treatment group, 36
      cases was completely relieved, 4 cases was partially relieved and the relief rate
      was 95.24%. In control group, 43 cases was completely relieved, 3 cases was
      partially relieved and the relief rate was 84.19%. There was no statistically
      significant difference between two groups (P<0.05). CONCLUSION: The self-made
      spinal expander is a minimal invasive technique, which can substitute the
      imported balloon. This technique can alleviate pain rapidly and recover the
      height of vertebral body.

PMID- 19102152
TI  - [Treatment of anterior dislocation of shoulder joint with manipulative method].

PMID- 19102153
TI  - [Role of pilose antler polypeptides on replicative senescence of rat
      chondrocyte].
AB  - OBJECTIVE: To observe the function of pilose antler polypeptides (PAP) on
      replicative senescence of rat chondrocyte subcultivated in vitro by means of PAP
      intervention and controlled experiment. METHODS: The 3rd generation chondrocytes
      were divided into blank group, and PAP groups with three different concentration
      of PAP which were passaged to the 4th generation. Meanwhile, the 2nd generation
      of chontrocytes were used as control group. The chondrocytes in different groups
      were detected with the method of histochemistry for S-A-beta-gal, flow cytometry
      for cell life cycle and proliferation index, alcian blue test for the content and
      structure of GAG of ECM, and RT-PCR for type II collagen and Aggrecan. Then PAP's
      function was observed regarding the appearance and functional status in the
      process of chondrocyte's senescence. RESULTS: PAP significantly inhibited
      chondrocyte's express of S-A-beta-gal (P<0.01), promoted chondrocyte's
      proliferation (P<0.01), reduced cell content on G1 phase, enhanced the content of
      GAG, type II collagen and Aggrecan of ECM (P<0.01). CONCLUSION: PAP can
      significantly resist rat chondrocyte senescence occurred in subcultivation.

PMID- 19102154
TI  - [Experimental study of peripheral nerve grafts for repairing of chronic spinal
      cord injury in adult rats].
AB  - OBJECTIVE: To explore the pathological mechanism in the repair of chronic spinal
      cord injury with free grafting of autoperipheral nerve tissues in rats. METHODS:
      The SD rats were used to establish SCI model with modified Allen method. The rats
      were divided into two groups at 12 weeks after the injury, each group had 20
      rats. In the experimental group, the sural nerves were removed epineurium and
      transplanted into SCI lesion by using microsurgical technique; and in the control
      group, the rats were treated without any operation. The survival and
      differentiation of the grafts, and the ability of repairing host spinal cord were
      observed under the light microscope at the postoperative 4th and 12th week.
      Regeneration rates of nerve tracts in spinal cord were evaluated by using HRP
      tracing technique at the postoperative 4th and 12th week. The morphological
      changes were observed at section of spinal cord and the motor functions of both
      hind legs of rats were detected. RESULTS: In the control group, spinal cord
      exhibited degeneration with cicatrices and cavitates. In the experimental group,
      peripheral nerve was almost survived, fused with the spinal tissue and axons
      could regrow into or span the place of injured spinal cord. Higher number of
      labeled nerve tracts in spinal cord were observed in experimental group, there
      was significant difference when compared with the control group. Motor function
      of hind legs of rats recovered significantly in the treatment group. CONCLUSION:
      Autoperipheral nerve graft tissues transplantation could survive and integrate
      with the host and have repairing effects on chronic spinal cord injury in rats.

PMID- 19102155
TI  - [Clinic application of skin flap based lateral supramalleolar branches of the
      peroneal artery].

PMID- 19102157
TI  - [Difficulties and strategies on the treatment of humeral supracondylar fracture].
AB  - Cubitus varus is the most difficult question in the treatment of humeral
      supracondylar fracture in children. In this retrospective study, 112 cases of
      humeral supracondylar fractures since 1988 were summarized and analyzed. Based on
      Liniansheng's evaluation standard,the therapeutic results were excellent in 49
      cases, good 43 and poor 20, and the incidence rate of cubitus varus was higher.
      The causes of cubitus varus were analyzed through the points of rotational
      displacement, ulnar deviation and fixation, and the corresponding strategies
      according to the causes were proposed to reduce the incidence rate of cubitus
      varus.

PMID- 19102156
TI  - [Application of ultrasonic microscopy in biomechanical properties measurement of
      cancellous bone].
AB  - OBJECTIVE: Ultrasound scanning can provide the information of acoustic impedance
      through the ultrasonic reflection theory. This study tries to introduce the
      application of the ultrasonic technique in predicting biomechanical properties of
      cancellous bone. METHODS: The rat femoral head embedded in plexiglass was used as
      the bone specimens for ultrasound scanning and the gray scale images scanned by
      ultrasound microscope were collected and analyzed. RESULTS: The value of acoustic
      impedance was calculated by analyzing the gray scale image. CONCLUSION: The
      application of ultrasonic microscopy can show more value about the microstructure
      of biomechanical properties of bone tissue.

PMID- 19102158
TI  - [Clinical analysis of 40 cases of ankle fractures combined with separation of
      lower tibiofibular joint treated by closed reduction and a single pin fixation].

PMID- 19102159
TI  - [Treatment of the lumbar disc herniation of sequestered type with Feng's spinal
      manipulation].
AB  - OBJECTIVE: To evaluate the clinical effect of the treatment for sequestered type
      lumbar disk herniation (SLDH) with FENG's spinal manipulation. METHODS: Forty-one
      patients (27 male, 14 female) were treated by FENG's spinal manipulation. The
      clinical results were measured by the Japanese and FENG's lumbar treatment
      standard and evaluated by scoring system for assessment of treatment for low back
      pain between pre- and post-treatment. To measure MRI sagittal index (SI) of
      lumbar disc herniation between pre- and post-treatment. RESULTS: The score of
      subjective symptoms and clinical signs increased obviously after treatment. There
      was no statistical difference of SI between pre- and post-treatment (P<0.05). The
      outcome of treatment was satisfying. CONCLUSION: The major pathologic change of
      SLDH is the single/multiple vertebral subluxation. FENG's spinal manipulation can
      correct the vertebral subluxation which leading to the series of clinical
      manifestations. The good clinical outcome may due to the alleviation of
      distortion and tension of dura and nerve root with the recovery of the spinal
      column's stability.

PMID- 19102160
TI  - [Treatment of different types of intertrochanteric fractures in the elderly with
      internal fixation].
AB  - OBJECTIVE: To study the treatment for the different types of intertrochanteric
      fractures in the elderly with internal fixation. METHODS: There were 62 cases of
      intertrochanteric fractures in the elderly (40 male and 20 female, aged from 60
      to 82 years, with an average age of 71 years). According to typing of Evans:
      there were 16 type I, 13 type II, 17 type III, 10 type IV and 6 type V. Internal
      fixation with three cannulated screws was applied for the 29 cases of type I and
      type II, with dynamic compression hip screw (DHS) for 33 cases of type III, III
      and V. RESULTS: After 1 to 4 years follow up (mean 2.5 years), according to the
      criteria of curative effect, 13 of 29 cases of type I and II (stable fracture)
      were excellent, 11 good and 5 poor, 18 of 33 cases of type III, IV and V
      (unstable fracture) were excellent, 12 good and 3 poor. CONCLUSION: Two different
      internal fixations can be used for different types of intertrochanteric fracture
      in the elderly. The internal fixation by three cannulated screws is often applied
      for the stable fracture (type I and II). For the unstable fracture (type III, IV
      and V), internal fixation with dynamic compression hip screw (DHS) is the first
      selection.

PMID- 19102161
TI  - [Dorsal approach and pi-shaped plate for treatment of distal radius fracture].
AB  - OBJECTIVE: To summarize the experiences in the treatment of distal radius
      fracture by locking pi-shaped plate internal fixation. METHODS: All the 32 cases
      (left 11, right 21) of unstable fractures of distal radius treated by locking pi
      plate fixation. Among them, 11 were male and 21 female with an average age of 36
      years (range, from 23 to 67 years). There were 16 cases of type B, 9 type C1 and
      7 type C2 according to AO classification. Autogeneic bone grafting was applied in
      27 patients. All the 32 cases were followed up. The range of motion of the wrist
      joint and radiographic parameters including palmar inclination, radial length and
      ulnar variance were evaluated. RESULTS: All the patients were followed up for 19
      to 28 months postoperatively (mean 25 months). Anatomical reduction was achieved
      in all the cases. Delayed union or non-union was not observed. According to
      rating scale of Gartland-Werley, 25 cases got excellent results and 7 good. No
      complications such as loss of reduction, tendon rupture occurred. CONCLUSION:
      Locking pi-shaped plate fixation is a reliable and effective method in the
      treatment of unstable fracture of distal radius.

PMID- 19102162
TI  - [Clinical outcome of minimally invasive internal fixation of pelvic ring injuries
      with cannulated screws].
AB  - OBJECTIVE: To evaluate the safety and reliability of percutaneous internal
      fixation for pelvic ring injuries with cannulated screws. METHODS: Forty-eight
      patients (21 male and 27 female, aged from 17 to 61 years with an average age of
      38 years) with unstable pelvic ring injuries were treated with closed reduction
      and percutaneous cannulated screws fixation under C-arm fluoroscopic guidance.
      According to Tile's classification, the patients were classified into type B1 in
      4 cases, B2.1 in 8, B2.2 in 10, B3 in 4, C1 in 11, C2 in 7 and C3 in 4. Among
      them, 39 patients were treated with anterior and posterior fixation, 4 were
      treated with anterior fixation, and 5 were treated with posterior fixation alone.
      Anteroposterior, inlet and outlet X-ray radiographs and CT scans of the pelvis
      were taken preoperatively to evaluate the stability and deformities, and after
      surgery the plain radiographs and CT scans were taken to evaluate the reduction
      and the location of screws. RESULTS: The average operative time was 55 minutes
      (range, 15 to 95 minutes), and the average intraoperative blood loss was 60 ml
      (range, 15 to 150 ml), no patient accepted blood transfusion during or after
      operation. All 48 patients were inserted 157 cannulated screws (mean 3.3, range 2
      to 8 per patient). Forty-two patients (135 screws) underwent postoperative pelvic
      CT scan and 91.11% (123 screws) of them was considered in optimal location; 7
      screws penetrated the wall of pelvis and acetabulam because of overlength (<0.5
      cm) or deviation, 5 screws interfered with the sacral canal or foramen.
      Fortunately, these 12 screws did not cause any symptom to the patients. The
      average follow-up period was 13 months (range 8 to 49 months), the displacement
      of injured pelvis was satisfactorily corrected in 45 patients (93.75%) and the
      fractures were healed at one stage. Among all patients, 40 cases (83.33%) had
      returned to their original works, 4 were still in the process of recovery at the
      last follow-up and the other 4 were unemployed as sciatic nerve injury or
      amputation. According to Lindahl improved standard of functional assessment of
      pelvic injury, the result was excellent in 35 cases, good 10 and fair 3, the
      average score was 78.7. CONCLUSION: With better understanding of the pelvic
      anatomy, and under C-arm fluoroscopic guidance, treatment of closed reduction and
      percutaneous cannulated screw internal fixation for unstable pelvic ring injuries
      is a safe, reliable and feasible method. The clinical outcome is satisfactory.

PMID- 19102163
TI  - [Surgical treatment of Lisfranc fracture-dislocations by reconstruction of three
      column with Kirschner wire fixation].
AB  - OBJECTIVE: To explore the effect of reduction and fixation with multi-Kirschner
      wires for treatment of Lisfranc fracture-dislocations. METHODS: There were 49
      patients (37 male and 12 female aged from 20 to 28 years old) involved in the
      study. According to the Myserson damage typing, type A in 12 cases, B1 in 3, B2
      in 28, C1 in 4 and C2 in 2. Kirschner wires were applied to fix and reconstruct
      the three-column in three directions according to the structural characteristic
      of midfoot. Reconstruction of three-column needed not only to reduce and to fix
      every single column, but also to establish union of the columns. RESULTS:
      According to the evaluation of AOFAS for midfoot, 14 cases were excellent (90
      to100), 22 cases good (80 to 89), 8 cases fair (70 to 79) and 5 cases poor (60 to
      69), with an average score of 84.200+/-9.663. CONCLUSION: The diagnosis and
      treatment of Lisfranc fracture-dislocations should comply with the theory of
      three-column reconstruction of foot arch, which can achieve the static balance of
      biomechanics and provide a stable environment for healing of fracture and soft
      tissue. Reduction and fixation with multi-Kirschner wires is an effective
      treatment method for Lisfranc fracture-dislocations.

PMID- 19102164
TI  - [Two-axis parallel method for tibial lengthening by metaphyseal osteotomy].
AB  - OBJECTIVE: To study the two-axis parallel method in bone lengthening. METHODS:
      Among 54 patients (male 28, female 26, mean age 22) who performed tibial
      lengthening by metaphyseal osteotomy using two-axis parallel method, 26 patients
      were poliomyelitis sequelae, 13 patients were inequality in limb length after
      trauma, 4 patients were achondroplasia, 6 patients were genetic short stature, 1
      patient was maculatum disease complicated with leg length discrepancy, 4 patients
      were pituitary dwarfism. RESULTS: All the patients were followed up and the
      duration ranged from 18 months to 45 months, with an average of 24.5 months. All
      patients had bone lengthened. The maximum increase of limb length was 12 cm and
      the minimum increase was 5 cm, averaged 6.2 cm. One patient had foot drop, 2
      patients had foot drop complicated with strephexopodia, 1 patient had serious
      pinhole infection, and 1 patient had delayed union of the bone. CONCLUSION: The
      two-axis parallel method tibial lengthening by metaphyseal osteotomy can reduce
      postoperative complications and simplify the operative procedure, which is an
      ideal method for bone lengthening.

PMID- 19102165
TI  - [Treatment of floating knee injuries with interlocked intramedullary nailing
      through a single incision].
AB  - OBJECTIVE: To investigate the technique and clinical effect of interlocked
      intramedullary nailing through a single incision on the treatment of floating
      knee injuries. METHODS: Thirty-eight patients of floating knee injuries included
      25 male and 13 female with an average age of 35.6 years ranging from 17 to 52
      years. All patients were treated by interlocked intramedullary nailing through a
      single incision. The clinical effect was evaluated postoperatively. RESULTS:
      Thirty-eight cases were followed-up for 8.6 to 15.4 months with an average of
      12.0 months. Thirty-seven cases gained bone healing and the time of fracture
      healing was from 2.7 to 6.9 months, with an average of 4.8 months. The nonunion
      of the distal femoral fracture was observed in 1 case with retrograde nailing,
      the revision operation was performed by plate and bone graft, and bony union was
      obtained. The results were excellent in 22 cases, good in 13 cases, fair in 2
      cases, and poor in 1 case. CONCLUSION: The treatment of floating knee injuries
      with interlocked intramedullary nailing through a single incision brings less
      damage, low infection rate, good fracture healing. It is an effective method for
      treating floating knee injuries.

PMID- 19102166
TI  - [Clinical analysis of the amputation for diabetic foot in 32 cases].
AB  - OBJECTIVE: To investigate the clinical rules of amputation for diabetic foot and
      analyse the perioperative problems. METHODS: Thirty-two patients with diabetic
      foot included 25 male and 7 female with an average age of 65.1 years, ranging
      from 51 to 78 years. All of them had amputation on single side. Among them, 23
      patients underwent amputation once, 8 patients had twice, 1 patient had three
      times. RESULTS: The patients were followed-up for 6 months to 1 year (average 8
      months). Two cases complicated with postoperative infection and gave up therapy,
      the other 30 cases gained wound healing finally and pain relief, recovery to
      normal life and work. CONCLUSION: Prevention and active treatment is the key for
      the diabetic foot. For the refractory infection the proper and correct amputation
      is necessary.

PMID- 19102167
TI  - [Treatment of occluded iliofemoral veins with great saphenous vein cross-over
      bypasses].
AB  - OBJECTIVE: To summarize clinical application experience of treatment of occluded
      iliofemoral veins with great saphenous vein cross-over bypasses. METHODS: From
      September 1998 to December 2005,6 patients(5 men, 1 woman) with occluded
      iliofemoral veins underwent great saphenous vein cross-over bypasses. They ranged
      in age from 36 to 52 years (mean, 41 years old). All patients had unilateral
      thigh and leg edema and swelling with accompanying pain. The normal contralateral
      great saphenous vein was dissected and it was tunneled across the super-pubic fat
      pad and anastomosed to the femoral vein or the proximal portion of great
      saphenous vein in distal to occluded iliofemoral veins. RESULTS: The
      postoperative course was uneventful. One case sustained superficial infection
      postoperatively at donor site and the gradual wound healed by daily wound
      dressings. At 1 to 3.5 years (mean 1.8 years) followed up, all patients had pain
      disappearance and obvious relief of the edema but some swelling. CONCLUSION:
      Great saphenous vein cross-over bypasses is effective operative method of
      treatment of occluded iliofemoral veins. The operation is relatively simple and
      safe.

PMID- 19102168
TI  - [Clinical study thoracolumbar Chance fractures: a report of 21 cases].
AB  - OBJECTIVE: To discuss the mechanism, clinical characteristics, diagnosis and
      treatment of thoracolumbar Chance fractures. METHODS: Among all the 21 patients,
      13 patients were male and 8 patients were female, ranging in age from 23 to 57
      years, with an average of 32 years. The injury was at the level of T11 in 3
      patients, at the level of T12 in 9 patients, at the level of L1 in 8 patients and
      at the level of L2 in 1 patient. According to Denis classification, 10 patients
      were type A, 2 type B, 5 type C, and 4 type D. All the patients were treated with
      pedicle screw internal fixation and posterior lateral fusion at the level of
      injury. RESULTS: Twenty-one patients had been followed up for an average of 18
      months (13 to 28 months). According to ASIA neurologic grading system, 4 cases in
      grade C or D recovered to grade E postoperatively and one case in grade B was not
      improved. Postoperative X-ray showed good reduction and fixation in all cases and
      no looseness or breakage in the fixation system. The results of postoperative
      back pain and function assessment were mostly satisfactory. CONCLUSION:
      Thoracolumbar Chance fractures are due to flexion-distraction injuries and
      regarded as unstable, which are uncommon and usually not present with a
      neurologic deficit. Reduction and stabilization with posterior pedicle screw
      internal fixation is suggested in patients with thoracolumbar Chance fractures.

PMID- 19102169
TI  - [Manipulative reduction combined with closed pinning fixation for the treatment
      of patella fracture: 36 cases report].

PMID- 19102170
TI  - [Treatment of distal radius fractures with being fixed at the supination
      position].

PMID- 19102171
TI  - [Experience of surgical treatment of intertrochanteric fractures by internal
      fixation].

PMID- 19102172
TI  - [Synovial chondromatosis of knee joint combined with femoral fracture: a case
      report].

PMID- 19102173
TI  - [Progress of vascularized bone grafting for the treatment of avascular
      osteonecrosis of the femoral head].
AB  - Avascular osteonecrosis of the femoral head is a common disease in orthopedic
      clinics. If the diagnosis can be made before collapse of the femoral head, the
      hip joint may probably be preserved by means of core decompression with or
      without bone grafting, osteotomies, as well as nonvascularized or vascularized
      bone grafting. Local pedicled bone grafts and free vascularized bone grafts can
      transfer the vascularized bone grafts into the necrotic area of the femoral head,
      which not only can replace necrotic bone with healthy bone, but also establish a
      new source of blood supply to the femoral head. The success rate in patients with
      different stages of osteonecrosis of femoral head was 80% at 5 years follow up.
      Free vascularized bone grafting for the treatment of avascular osteonecrosis of
      the femoral head can obtain a higher success rate.

PMID- 19102174
TI  - [Study on the therapeutic effects of external fixation with splint and plaster
      cast for the treatment of double fractures of ulna and radius].

PMID- 19102175
TI  - [Prevention of early complications of surgical treatment for scoliosis].

PMID- 19102176
TI  - [Analysis of complications in scoliosis surgery].
AB  - OBJECTIVE: To analyze the complications occurred in scoliosis surgery and
      evaluate its prevention strategy. METHODS: From June 2002 to May 2007, 86 cases
      of idiopathic scoliosis were treated. There were 21 male and 65 female with an
      average age of 17.8 years(range, from 8 to 22 years). According to Lenke
      classification, 33 cases were type 1, 10 type 2, 18 type 3, 5 type 4, 10 type 5
      and 10 type 6. Five cases were Risser 0 to I, 20 cases II to III, 61 cases 1V to
      V. Cobb angles were from 45 degrees to 85 degrees (mean 60.35 degrees). The
      pedicle screw technique was used to correct all the scoliasis, and the results
      and complications were studied. RESULTS: The average operation time was 3.2 hours
      and average blood loss volume was 1000 ml (800-2400 ml), 924 pedicle screws were
      inserted and the average postoperative Cobb angle was 18.46 degrees. All the
      patients were followed up for 5 to 40 months(mean 20.5 months). The complications
      were as following: 1 case of spinal cord injury; 25 screws misplaced; 2 cases of
      nerve root injury; 1 case of pleura injury; 1 case of superior mesenteric artery
      syndrome; 3 cases of wound infection; 2 cases of trunk decompensation; 1 case of
      junction kyphosis; 3 cases of implant loosening; 2 cases of pseudarthrosis; 1
      case of crankshaft phenomenon; 2 cases of flatback syndrome. CONCLUSION: Many
      kinds of complications may occur in scoliosis surgery. Exactitude procedures of
      diagnosis and surgery for the scoliosis are the key to decrease and prevent the
      complications related to the operation.

PMID- 19102177
TI  - [Thoracic complications of convex thoracoplasty in patients with thoracic
      scoliosis].
AB  - OBJECTIVE: To analyze thoracic complications related to the convex thoracoplasty
      for the treatment of rib hump deformity in patients with thoracic scoliosis.
      METHODS: Between December 2003 and September 2007, 548 patients with thoracic
      scoliosis underwent posterior spinal correction and the convex thoracoplasty.
      There were 167 male and 381 female, with an average age of 16.1 years (range, 12
      to 38 years). The mean preoperative rib prominence was 35 degrees (range, 16
      degrees to 50 degrees). RESULTS: The mean number of resected ribs was 4.1. The
      mean rib prominence was 7 degrees (range 2 degrees to 17 degrees) after
      operation. No death happened. Thoracic complications related to the thoracoplasty
      consisted of respiratory insufficiency in 1 (0.2%) patient,intraoperative tear of
      parietal pleura in 29 (5.3%), with a subsequent pleural effusion in 6 and
      pneumothorax in 3. In the other patients, no obvious tear of parietal pleura was
      found during operation. However, 6 (1.1%) patients had pleural effusion after
      operati on. CONCLUSION: The thoracic complications related to convex
      thoracoplasty can be decreased by improving the surgical skill and using
      respiratory function monitoring.

PMID- 19102178
TI  - [Persistent lavage with antibiotic solution and antibiotic-impregnated bone
      grafting with skin flap or muscle flap in the treatment of complicated chronic
      osteomyelitis].

PMID- 19102179
TI  - [Analysis of complications associated with internal fixation for lumbar
      spondylolisthesis].
AB  - OBJECTIVE: To evaluate the therapeutic effects of lumbar spondylolisthesis by
      decompression, instrumentation and posterolateral fusion, and study the causes of
      the related complications and its method for the prevention. METHODS: One hundred
      and sixty-five cases with grade I to II spondylolisthesis from February 1991 to
      May 2007 were retrospectively analyzed. All cases were treated by posterior
      lumbar canal decompression, reduction with pedicle screw system and fusion with
      posterolateral bone grafting. Among them,there were 55 male and 110 female with
      an average age of 53.6 years. Besides, one segment was involved in 161 cases and
      two segments involved in the rest of them. RESULTS: The complications were
      divided into either intraoperative postoperative complications. Intraoperative
      complications were 5 cases (3.0%) there were 4 cases with dura tear and 1 case
      with nerve root injury. Postoperative complications were 18 cases (10.9%), there
      were 3 cases with cerebrospinal fluid leakage, 1 case with wound infection, 2
      cases with hematoma,5 cases with transient neurological deficits, 1 cases with
      implant failures and 6 cases with pseudarthrosis formation. CONCLUSION: Good
      clinical results of lumbar spondylolisthesis can be obtained by posterior
      reduction and fixation with pedicle screw system. However,operation skills and
      strict indications play an important role in the prevention of complications.

PMID- 19102180
TI  - [Application of Giebel condyle plate in the treatment of osteoarthritis with genu
      valgum].

PMID- 19102181
TI  - [Preliminary studies on revision of the failed surgery for lumbar
      spondylolisthesis].
AB  - OBJECTIVE: To study the causes of failure in the treatment of lumbar
      spondylolisthesis, and revision techniques and therapeutic effects. METHODS:
      Eight cases with failed spondylolisthesis surgery were treated. There were 3 male
      and 5 female with an average age of 54 years old,ranging from 42 to 71 years.
      Among them, there were 6 cases of pedicle screws breakage, 1 case of fusion cage
      sinking and pedicle screws breakage, 1 case of osteoporosis and pedicle screws
      loosening. Their clinical symptoms included deformity, local pain, leg pain and
      numbness. The revision surgery was performed by the posterior decompression,
      instrumentation,intervertebral and posterolateral bone grafting, in which large
      diameter or long screws were applied for pedicle screws fixation. RESULTS: All
      cases were followed-up from 6 to 24 months after revision(mean, 16 months). The
      clinical result was satisfied and the excellent or good results were 87.5%. There
      was no infection and other major complications. All patients had achieved solid
      fusion. CONCLUSION: Poor technique and skill are considered as the primary causes
      leading to surgical failure of lumbar spondylolisthesis. The satisfactory outcome
      could be obtained by appropriately using the revision techniques.

PMID- 19102182
TI  - [The clinical application of manipulation for old both-bones fracture of
      forearm].

PMID- 19102183
TI  - [A comparisive study between intramedullary interlocking nail and plate-screw
      fixation in the treatment of tibial shaft fractures].
AB  - OBJECTIVE: To evaluate the effects of tibial shaft fractures treatment with plate
      screw or intramedullary interlocking nail. METHODS: Thirty-five fractures were
      treated with intramedullary interlocking nail. Tape A, B and C were 11, 18 and 6
      cases respectively according to AO classification. Forty-five fractures were
      treated with plate-screw system. Type A,B and C were 10,22 and 13 cases
      respectively. The mean time between injury and operation was 3 days and 3.5 days
      respectively. The patients were evaluated with operation time,range of
      motion,time of bone union,and complications after a mean followup of 13
      months(range 8 to 26 months). RESULTS: The mean operation time and the mean range
      of motion of the ankle and knee were found similar in both groups. The average
      dorsiflexion angle of ankle was 13 Degrees (0 degrees to 20 degrees) in locked
      intramedullary nailing group and 11 degrees (0 degree to 20 degrees) in plate
      group. The average plantar flextion angle of ankle was 41 degrees (30 degrees to
      50 degrees) in locked intramedullary nailing group and 47 degrees (30 degrees to
      50 degrees) in plate-screw group. The mean time of bone union was 3.3 months with
      intramedullary nailing and 3.5 months with plate-screw fixation. Length
      discrepancy occurred in only two patients (2 and 2.5 cm) with intramedullary
      interlocking nail. One patient treated by intramedullary interlocking nail for a
      type III open fracture occured osteomyelitis. Plain radiographs showed rotation
      in two patients with intramedullary interlocking nail and angulation in 3
      patients with plate-screw fixation, which were distal-third tibial fractures.
      CONCLUSION: Plate-screw osteosynthesis could attain satisfactory results in
      uncomminuted tibia shaft fractures, and locked intramedullary nailing is more
      appropriate in comminuted fractures.

PMID- 19102184
TI  - [The randomized controlled trial of influences of T shape approach on the
      function of knee joint in the treatment of proximal tibial fractures].
AB  - OBJECTIVE: To investigate the clinical value of T shape approach in the treatment
      of proximal tibial fractures. METHODS: One handrend and thirteen patients of
      proximal tibial fractures were randomly divided into two groups. Group A: 62
      cases underwent the traditional exposure approach. According to Schatzker
      classification,the cases of II to VI type was 25, 10, 16, 6, 5 respectively.
      Group B:51 cases underwent T shape approach ahead of knee joint, the cases of II
      to VI type was 21, 8, 13, 5, 4 respectively. All data were analyzed by SPSS 10.0
      to compare operation time, blood loss, duration of hospitalization, healing time,
      the time of osseous union and complications after operation. RESULTS: Sixty
      patients in group A and 50 patients in group B were followed-up from 12 to 24
      months. (1) Operation time:group B was longer than A (P < 0.01). (2) Mean blood
      loss and duration of hospitalization was the same. (3) Clinical healing
      time:group B was shorter. (4) Mean time of osseous union: 48 group B was shorter.
      Function of knee: group B was better than group A. (Complication: group B was
      less than group A. CONCLUSION: As compared with traditional exposure approach, T
      shape approach of knee joint had advantages of small scar, fewer complications,
      faster union of fracture and earlier recovery of joint function. The approach is
      valuable for the treatment of proximal tibial fractures.

PMID- 19102185
TI  - [Comparative study on reconstruction of anterior cruciate ligaments with
      allografts and hamstring tendon under arthroscopy].
AB  - OBJECTIVE: To evaluate the effect of reconstruction of anterior cruciate
      ligaments (ACL) with allogeneic tendon or autologous hamstring tendon under
      arthroscopy. METHODS: Thirty-two cases of ACL injury (3 cases compound with PCL
      injury) were reviewed. All the patients were divided into two groups randomly.
      Fifteen cases were reconstructed with hamstring tendon, including 12 male and 3
      female with the age ranging from 23 to 61 years. Seventeen cases were
      reconstructed with allograft, including 11 male and 6 female with the age ranging
      from 17 to 57 years. The tendons were fixed with absorbable or Ti screws. All
      patients were recorded symptoms,physical signs and Lysholm Scores two weeks after
      operation,and functional rehabilitation of knee six months after operation.
      RESULTS: All cases were followed up from 6 to 8 months. Pain and clinical
      symptoms disappeared and the function of knee joint was improved in all patients.
      Five patients of allograft with positive Lachman test result,one with severe
      graft rejection was found complete absorption of allograft under arthroscopy. No
      significant differences were seen in Lysholm Score between the two groups,average
      (88.5 +/- 7.2), (93.2 +/- 8.5) after operation (P > 0.05). CONCLUSION: The
      effects of reconstruction of cruciate ligaments with allogeneic tendon or
      autologous hamstring tendon under arthroscopy are more satisfying. But there are
      more symptoms and obvious individual differences in the earlier stage of
      rehabilitation. So reconstruction of cruciate ligaments under arthroscopy using
      autologous hamstring tendon should be performed as far as possible.

PMID- 19102186
TI  - [A randomized controlled trial of rotatory reduction manipulation and acupoint
      massage in the treatment of younger cervical vertigo].
AB  - OBJECTIVE: To explore the effects of rotatory reduction manipulation and acupoint
      massage on blood flow velocity of vertebrobasilar artery (VBA) in younger
      cervical vertigo of high velocity,and to observe the difference of clinical
      therapeutic effect between two manipulations. METHODS: Seventy-six patients who
      diagnosed as high flow velocity of younger cervical vertigo were randomly divided
      into rotatory reduction manipulation group (group A, 38 cases)and acupoint
      massage group (group B, 38 cases). The changes of flow velocity of VBA before and
      after treatment were observed using transcranial Doppler (TCD) and the
      therapeutic effects were observed also. RESULTS: The mean flow velocity in left
      vertebral artery (LVA)and basilar artery (BA)of group B and in BA of group A were
      significantly decreased as compared with those before treatment (P < 0.05, P <
      0.01) 1 week after treatment,and there was significant difference in the change
      of mean flow velocity in LVA between two groups (P < 0.01). The mean velocity in
      LVA, right vertebral artery (RVA) and BA were obviously lower than thosfre before
      treatment in two groups (P < 0.01) 3 weeks after treatment. There was obvious
      difference in LVA, RVA between two groups (P < 0.01). The therapeutic effect of
      group B was superior to that of group A (P < 0.05). CONCLUSION: The effect of
      acupoint massage on flow velocity of VBA was superior to that of rotatory
      reduction manipulation, and the therapeutic effect of acupoint massage might be
      better than that of rotatory reduction manipulation in treating younger cervical
      vertigo of high flow velocity.

PMID- 19102187
TI  - [Manipulative reduction for lumbar intervertebral disc herniation: a controlled
      clinical trial].
AB  - OBJECTIVE: To investigate the effects of manipulative reduction on pain and
      clinical curative effect in patients with lumbar intervertebral disc herniation.
      METHODS: Eleven thousands one hundred and twenty-eight patients with lumbar
      intervertebral disc herniation from our hospital were enrolled from November 1986
      to June 2007. They were randomly divided into control group and treatment group.
      Patients of the control group received lumbar traction and various
      physiotherapies. Patients of the treatment group received manipulative reduction,
      besides the treatment in the control group. The treatment was performed once a
      day,ten times as a course. Curative effects were assessed three courses later.
      Pain was evaluated by visual analogue scale before and after the treatment.
      RESULTS: No significant difference in the score of visual analogue scale was
      found before the treatment in the two groups (P > 0.05). As compared with the
      score before treatment,it was decreased by 4.73 points after treatment in the
      control group, and decreased by 6.37 points in the treatment group. The decrease
      was more significant in the treatment group than the control group (P < 0.01).
      The healing rate was 47.28% and total effective rate was 96.37% in the control
      group; The healing rate was 73.44% and total effective rate was 98.61% in the
      treatment group (P < 0.01). CONCLUSION: Manipulative reduction for lumbar
      intervertebral disc herniation can remarkably relieve lumbar pain and improve
      clinical curative effect.

PMID- 19102188
TI  - [Effects on rats' bone mineral density and bone biomechanics by suspensory
      simulated weightlessness and removing suspension].
AB  - OBJECTIVE: To study the effects on rats' bone mineral density and bone
      biomechanics by suspensory simulated weightlessness and removing suspension.
      METHODS: Twenty Wistar rats were divided into two groups randomly as control
      group and model group. Suspend the model group rats for 14 days, then remove
      suspension and continue to feed for another 14 days. Feed control group rats for
      28 days. Detect the bone mineral density (BMD) in vivo of cranial bone, second
      thoracic vertebra, fourth lumbar vertebra, pelvis, right radioulna and right
      femoral bone of each group at the 14th day. At the 28th day,execute all the rats
      and take out of right femoral bone and fourth lumbar vertebra for detecting BMD
      and the intensity of biomechanics. RESULTS: At the 14th day in experiment, being
      compared with control group,the BMD of femoral bone, pelvis and lumbar vertebra
      in model group decreased significantly (P < 0.001, P < 0.001, P < 0.01) and the
      change of BMD of cranial bone, thoracic vertebra and radioulna in model group was
      not remarkable (P > 0.05). At the 28th day in experiment, the BMD of femoral bone
      and lumbar vertebra, the maximal load of femoral bone decreased significantly in
      model group as compared with control group (P < 0.01, P < 0.001, P < 0.01).
      CONCLUSION: BMD in vive body showed that suspensory simulated weightlessness for
      14 days could cause disorder of bone metabolism and remarkable mineral loss of
      weight bearing bone, even BMD and biomechanical intensity of weight bearing bone
      decrease obviously when removing suspension for 14 days. The results suggest that
      the disorder of bone metabolism could not be recovered in short time.

PMID- 19102189
TI  - [A biomechanical study of anterior screw fixation for type II odontoid fracture
      with anteroinferior-posterosuperior fracture line].
AB  - OBJECTIVE: To investigate the biomechanical effect of anterior screw fixation on
      the type II fractured odontoid process. METHODS: Twenty fresh human C1-C2
      vertebrae specimens were harvested and randomly divided into three groups. The
      angle of type II fracture line was 0 degree in group I (n=6), 17 degrees in group
      II (n=8) and 25 degrees in group III (n=6). The fractures were treated by
      anterior screw fixation. Insertion torque,maximal axial pullout force and
      stiffness of the bone-screw were tested. RESULTS: There was no significant
      difference of screw insertion torque and the pull-out strength between each
      group. The displacement of the odontoid fragment had an association to the angle
      of the fracture line,the displacement of the small angle was significantly higher
      than that of the large one (P < 0.5). No significant difference of structure
      stiffness of the bone-screw was found between each group. CONCLUSION: Anterior
      screw fixation is feasible for type II odontoid fracture with certain fracture
      line extends from anteroinferior to posterosuperior.

PMID- 19102190
TI  - [Adhesion, proliferation and osteodifferentiation of bone mesenchymal stem cells
      on PLGA-[ASP-PEG] tri-bolck polymer scaffolds].
AB  - OBJECTIVE: To explore the adhesion,proliferation and osteodifferentiation of bone
      mesenchymal stem cells (BMSCs)on the prepared lactic acid/glycolic acid/asparagic
      acid-co-polyethylene glycol(PLGA-[ASP-PEG])tri-block polymer scaffolds. METHODS:
      Modified PLGA with polyethylene glycol (PEG) and asparagic acid(ASP)that has many
      liga nds,and then the synthesis PLGA-[ASP-PEG] tri-block polymer material was
      prepared. BMSCs were cultured in PLGA-[ASP-PEG] polymer material and poly lactic
      acid-co-glycolic acid(PLGA)were used as control group. Precipitation method, MUT
      assay and total cellular protein detection were used to test the adhersion and
      proliferation of BMSCs. After the third generation of BMSCs was cultured on PLGA
      [ASP-PEG] tri-block polymer scaffolds for 14 day and 28 day with osteogenic
      supplements,the osteodifferentiation of MSCs were observed through alkaline
      phosphatase(ALP) staining and calcium tubercle staining. RESULTS: BMSCs grew
      adherent to the surface of PLGA-[ASP-PEG] polymer scaffolds and the number of
      BMSCs was much higher than that of PLGA. The precipitation method suggested that
      adhesion and proliferation of BMSCs on the surface of PLGA-[ASP-PEG] was much
      higher than the control group (P < 0.05). MTU assay showed that after BMSCs were
      cultured for 20 days,the absorbance A of PLGA-[ASP-PEG] polymer scaffolds and
      PLGA were 1.336 and 0.780 respectively. Total cellular protein could image the
      adhersion and proliferation of BMSCs indirectly. After BMSCs were cultured for 12
      days,the total cellular protein of PLGA-[ASP-PEG] and PLGA were 66.44 microg/pore
      and 41.23 microg/pore respectively. PLGA-[ASP-PEG] polymer scaffolds had well
      biocompatibility and cell adhersion. The positive results with ALP staining and
      calcium tubercle staining in both groups indicated tri-block polymer scaffold and
      its degradations had no effect on osteodifferentiation. CONCLUSION: PLGA-[ASP
      PEG]could improve the adhesion and proliferation of seed cells on bone
      matrixmaterial, maintain the morphous of seed cells and had no obvious effect on
      cell osteodifferentiation.

PMID- 19102191
TI  - [Protective effect of velvet antler polypeptide (VAP) on rats with the spinal
      cord injury].
AB  - OBJECTIVE: To investigate the protective effect of antler polypeptide on the rats
      with spinal cord injury (SCI). METHODS: The model rats were treated with
      different doses of antler polypeptide, and its effect on motor function, ethology
      and pathological changes of spinal cord of the rats observed. RESULTS: Seven days
      after treatment with different doses of antler polypeptide, rat's motor activity
      was recovered in some extent. Significant difference (P < 0.001)was found between
      the antler polypeptide treatment group and operation group. The effect could be
      enhanced by increase of the doses. We observerd the effect on the pathological
      change of spinal cord in rat, and found the tissue edema and inflammatory
      infiltration were relieved after treatment with different doses of antler
      polypeptide, especially in the dose of 15 mg antler polypeptide. CONCLUSION:
      Antler polypeptide can promote the motor function recovery in SCI rats, and its
      action is dose-dependent.

PMID- 19102192
TI  - [Effect of qianggu drink ([Chinese characters: see text]) on bone
      histomorphometry of lumbar vertebrae in ovariectomized rats].
AB  - OBJECTIVE: To observe the effect of Chinese herbal medicine Qianggu drink
      ([Chinese characters: see text]) on bone histomorphometry of lumbar vertebrae in
      ovariectomized rats and to explore its mechanism. METHODS: Sixty female SD rats
      (weight 230 to 280 gram) were randomized into three groups: Qianggu drink
      ([Chinese characters: see text]) group (treatment group), Miacalcic group
      (control group) and blank group. The osteoporosis model was established
      successfully after all rats were ovariectomized for 10 weeks. The treatment group
      was used intragastric infusion with Qianggu drink ([Chinese characters: see
      text]) 0.001 ml/kg once a day. The control group was used hypodermic injection
      once a day with Miacalcic 0.72 U/kg. Five rats were killed respectively and the
      lumbar specimens were taken and cut for bone histomorphometric analysis at 45,
      90, 135 and 180 days after the treatment. RESULTS: The thickness of trabecular
      bone in treatment group had the statistical significance with control group at
      135 days after ovariectomized rats were given the medicine. The data of BV/TV and
      the thickness and space of trabecular bone had statistical significance compared
      with control group and blank group 180 days later. CONCLUSION: Qianggu drink
      ([Chinese characters: see text]) could effectively improve the histomorphometry
      indexes. The mechanism probably plays by stimulating osteogenesis and inhibiting
      the cytoactive of osteoclast and the trend of bone transform.

PMID- 19102193
TI  - [Therapeutic strategies of grade-III open fractures of tibia and fibula].
AB  - OBJECTIVE: To explore early treatment and technique of grade-III open fracture of
      tibia and fibula and to summarize the experience of the treatment with external
      fixation. METHODS: The retrospective analysis were carried out in 168 cases of
      grade-III open tibial and fibular fractures. One hundred and twenty cases were
      treated with external fixation,and others were treated with intramedullary nail
      or amputated. Among 120 patients treated with external fixation in early stage,
      86 were male and 34 were female. The age ranged from 18 to 67 years with an
      average of 36.8 years. RESULTS: One hundred and eleven patients achieved the
      excellent or good results, some of them underwent later repair of soft tissues.
      One case was nonunion because of infection and malreduction, and amputation in
      later stage in 8 cases. CONCLUSION: Treatment with external fixation in early
      stage is an ideal method for grade-III open fractures of tibia and fibula. Good
      reduction integrated with simple internal and external fixation is favorable for
      the repair of soft tissue and union of fracture.

PMID- 19102194
TI  - [To explore the relation between erythrocyte sedimentation rate and postoperative
      recurrence of spinal tuberculosis].
AB  - OBJECTIVE: To explore the relation between erythrocyte sedimentation rate(ESR)
      and postoperative recurrence of spinal tuberculosis. METHODS: Eighty cases (36
      males and 44 female,ranging from 20 to 71 years with an average of 38.2 years)of
      spinal tuberculosis treated with focus debridement were divided into two groups
      according to the preoperative value of ESR: Group A (ESR > or = 40 mm/h) and
      Group B (ESR < 40 mm/h). Patients in two groups were treated by the same method.
      The postoperative recurrences in two groups were analyzed. RESULTS: All the
      patients were followed up. The recurred cases were 5 in Group A and 4 in Group B.
      There is no significant difference between two groups. CONCLUSION: ESR is not the
      key factor to choose the right operative time to perform debridement.

PMID- 19102195
TI  - [Early open reduction of acute incarceratied metacarpophalangeal dislocation].
AB  - OBJECTIVE: To explore the mechanism and the treatment of acute incarcerated
      metacarpophalangeal dislocation. METHODS: Seven patients (6 male and 1 female)
      with acute incarcerated metacarpophalangeal dislocation admitted from 1997 to
      2006 were studied retrospectively. The age ranged from 8 to 33 years(mean 17
      years). All the types were the dorsal dislocation. The dislocation were occurred
      on index finger in 3 cases, thumb in 2 cases, middle finger in 1 case and small
      finger in 1 case. RESULTS: All the patients were followed up from 3 to 42 months
      with an average time of 21 months. Operative finding revealed the rupture of
      volar capsule and entrapment of metacarpal head. The joint function and
      postoperative X-ray showed anatomical reduction were good in all the patients.
      CONCLUSION: Repeated manipulative reduction should not be advocated if the close
      reduction was not successful. In order to avoid influencing the joint
      function,early open reduction of acute complex metacarpophalangeal dislocation is
      necessary.

PMID- 19102196
TI  - [Surgical treatment of talar neck fractures].
AB  - OBJECTIVE: To explore the clinical effect of talar neck fractures treated by open
      reduction and internal fixation with screws. METHODS: Among 28 cases in the
      study, 20 cases were males and 8 cases were female. The age ranged from 22 to 72
      years with an average of 38 years. Based on the Hawkins classification,there were
      6 cases of type I,18 of type I and 4 of type II. They were treated by open
      reduction and internal fixation with screws. RESULTS: Twenty-eight cases were
      followed up for 1 to 7 years(mean 2.8 years). The evaluation of the results by
      Hawkins functional rating scale revealed excellent in 14 cases,good in 9 cases,
      fair in 3 cases and poor in 2 cases. The excellent and good rate were 83.2%.
      Osteonecrosis occurred in 5 cases with 3 of type II and 2 of type III fractures.
      Two of 3 cases with talar displacement were found with osteonecrosis or painful
      arthritis. The subtalar arthritis occurred in 6 cases, 3 of which were associated
      with ankle arthritis. Two cases underwent arthrodesis because of painful
      arthritis of the subtalar joint or osteonecrosis of the talar body. Wound
      infection and anteromedial skin necrosis of the ankle were not found. CONCLUSION:
      Treatment of talar neck fractures could obtain satisfactory clinical results
      through open reduction and internal fixation with screws. Protection of the
      residual blood supply, anatomically reduction and stable fixation are essential
      for successful treatment of talar neck fractures.

PMID- 19102197
TI  - [Flexor digitorum (hallucis) longus muscle tendon transfer in the repair of old
      rupture of the Achilles tendon].
AB  - OBJECTIVE: To explore the operative technique of repair and its curative effect
      of old rupture of the Achilles tendon with flexor digitorum (hallucis)longus
      tendon transfer. METHODS: From Nov 2001 to May 2005, 13 patients who had old
      rupture of the Achilles tendon were treated with this operative technique. Five
      of them were treated with flexor digitorum longus tendon transfer and 8 with
      flexor hallucis longus tendon. All patients had the history of closed injury of
      Achilles tendon(9 male and 4 female, 8 left feet and 5 right feet). The age
      ranged from 32 to 69 years(mean 41 years). OPERATIVE TECHNIQUE: flexor digitorum
      (hallucis)longus tendon was cut down alternatively. The distal end of flexor
      digitorum longus tendon should be sutured to flexor hallucis longus tendon if the
      flexor digitorum longus tendon was cut. The distal end of flexor hallucis longus
      tendon should be sutured to flexor digitorum longus tendon if the flexor hallucis
      longus tendon was cut. The proximal end of tendon to be cut down was sew up a
      suture line and pulled out from the incision to reveal the Achilles tendon. A
      transverse hole was drilled through the anterior aspect of the insertion of the
      tendon of the calcareous, and then drilled upward perpendicularly. The two holes
      were cross-connected by towel clamp. The flexor digitorum (hallucis)longus tendon
      to be transferred was pulled through the first hole from wall outward and upward,
      and then pulled through superior extremity of the second hole. The end of tendon
      was sutured firmly with the Achilles tendon. RESULTS: All patients have no
      infection or re-rupture during follow-up (average 24 months;range 11 to 54
      months). There was no subsequent hammer-toe deformity. Dorsiflexion at least to
      neutral and normal plantar flexion were obtained in all patients. According to
      Arner-Lindholm standard,the final results were excellent in 9 patients(6 cases
      were used flexor hallucis langus tendon, and 3 cases were used flexor digitorum
      longus tendon),good in 3 patients(2 cases were used flexor hallucis longus tendon
      and 1 case was used flexor digitorum longus tendon) and poor in 1 patient used
      with flexor digitorum longus tendon. CONCLUSION: The repair of old rupture of the
      Achilles tendon with flexor digitorum (hallucis) longus tendon transfer is an
      ideal and effective method. Furthermore, the use of flexor hallucis longus muscle
      tendon tends to be more reasonable.

PMID- 19102198
TI  - [Surgical treatment of pronation and supination external rotation trimalleolar
      fractures].
AB  - OBJECTIVE: To explore the operative method and its clinical effects of pronation
      and supination external rotation trimalleolar fractures. METHODS: From March 2000
      to July 2006,42 patients of the pronation and supination external rotation
      trimalleolar fractures treated with open reduction and internal fixation. Thirty
      one were males and 11 were females,with an average age of 40.5 years (from 19 to
      76 years). Four cases were open fractures and 38 cases close fractures. The
      fractures were classified as pronation-external rotation (grade IV) injury in 18
      cases and supination-external rotation (grade IV)in 24 cases according to the
      system of Lauge-Hansen. The time of injury to operation was 2 hours to 27 days.
      The medial, lateral and posterior malleolus were exposed by standard anteromedial
      and Gatellier-Chastang approaches. The reduction and internal fixation started
      with the posterior,then the medial and the lateral malleolus and distal
      tibiofibular syndesmosis in sequence. The anteroposterior, lateral and mostise X
      ray films were taken after operation. RESULTS: All the patients were followed up
      for an average time of 13.5 months(from 6 to 24 months). The time of union was
      from 12 to 16 weeks. The results were excellent in 20,good in 16, fair in 4 and
      poor in 2 cases according to Baird-Jackson ankle scoring system based on pain,
      stability, walking ability,range of motion and radiological manifestations. The
      excellent and good rate was 85.7%. There were no infection,malunion and nonunion
      of the fractures except that the inserted screw to distal tibiofibular
      syndesmosis was broken in 1 case. CONCLUSION: The key of operative treatment is
      to restore the anatomy of ankle and to regain the ankle function maximally.

PMID- 19102199
TI  - [Experience of the treatment of gluteal contracture in small incision].

PMID- 19102200
TI  - [Treatment of pyogenic infection of bone and joint by iodophor irrigating].

PMID- 19102201
TI  - [Extension restoration and paper splint fixation for the treatment of fractures
      of the neck of the fifth metacarpal].

PMID- 19102202
TI  - [Modified operation through small incision for the treatment of rupture of the
      long head of the biceps tendon].

PMID- 19102203
TI  - [Minimally invasive treatment for humerus surgical neck fracture].

PMID- 19102204
TI  - [Treatment of comminuted fractures of distal tibia with limited internal fixation
      and over-articular external fixators].

PMID- 19102205
TI  - [Closed reduction and percutaneous Kirschner-wire fixation for the treatment of
      supracondylar fractures in children: a report of 37 cases].

PMID- 19102206
TI  - [Treatment of pubic symphysis diastasis with plate fixation].

PMID- 19102207
TI  - [Solitary bone cyst in both calcaneuses: a case report].

PMID- 19102208
TI  - [Surgical treatment of scapular fractures].
AB  - Scapular fracture is not very common,which typically occur in patients who have
      sustained high-energy direct injury to the shoulder. Eighty to ninety-five
      percent of patients with scapular fractures have been associated with multi
      injuries. The physical examination should uncover injuries to the brachial
      plexus,axillary artery as well as ipsilateral musculoskeleton. The goal of
      treatment for scapular fractures is to restore an effective and functional joint
      without pain. Displaced intra-articular glenoid fracture,double disruptions of
      the shoulder suspensory complex, floating shoulder injury, significant angulation
      and displacement of the scapular neck should undergo surgical treatment. Fracture
      fixation must be stability that allows early motion of shoulder. After operation,
      patients should insist on functional exercises of shoulder until union of
      fracture was solid.

PMID- 19102209
TI  - [Studies on the progress of premixed calcium phosphate cements].
AB  - Calcium phosphate cement (CPC) is considered as an important bone repairing
      materials due to its excellent biocompatibility, osteoconductivity and
      remodellability, the study about its performance is still a hot topic in the
      field of bone tissue engineering. Premixed calcium phosphate cements (PCPC) has
      advantages that can save operatiion time,be convenient to the operation and
      preservation compared with the traditional way of immediately mixing calcium
      phosphate cement. PCCP has overcome the shortcomings of uneven and inadequate
      mixing, and can be arbitrarily remodeled according to the shape of defect, thus
      researches on PCCP has also become more and more interested

PMID- 19102210
TI  - [Progress on interface membrane around prostheses].
AB  - Aseptic loosening is one of the most frequent long-term complications after joint
      replacement,which limits the service life of prostheses. A lot of studies have
      been focused on interface membranes around prostheses recently. In interface
      membranes, there are plenty of macrophagocytes and desmocytes,which play vital
      roles in osteolysis. This study gave a review of interface membrane including its
      formation, cellulosity, osteolysis factor, immunity reaction and turnover. The
      advances of interface membranes will help us to comprehend the pathogenesy and
      treatment of the aseptic loosening.

PMID- 19102211
TI  - [Current treatment strategies for patients with cancers of the head and neck].
AB  - Head and neck squamous cell cancer (HNSCC) management is evolving rapidly.
      Approaches under exploration include induction chemotherapy, altered
      fractionation radiation with chemotherapy, intensity modulated radiation therapy
      (IMRT) and the use of biologically targeted drugs to enhance radiation. The goal
      of the new methods is improving the effectivity without increasing the toxicity.
      This article will focus maily on locally advanced HNSCC, which frequently remains
      a clinical challenge, review state-of-the-art therapy and introduce promising
      novel terapies. For the future the incorporation of new agents, the use of novel
      biomarkers to accurately assess and individualize therapy, and expanded
      supportive care approaches will play an increasingly important role.

PMID- 19102212
TI  - [The origin and formation of chromosomal translocations in multiple myeloma].
AB  - Multiple myeloma is a malignant disease of terminal developmental stages of B
      lymphocytes, i.e. plasma cells. During the progress of the disease genetic
      changes are cumulated in these cells which are the cause of their fully malignant
      phenotype. The affection of plasma cells is characterized by the presence of
      various numerical and structural chromosomal aberrations. A frequent cytogenetic
      finding is the presence of reciprocal translocations originating within the
      process of the so-called illegitimate switch recombination, affecting the gene
      for heavy chains of immunoglobulins (IgH) in the 14q32 chromosome area. As a
      result of this recombination the oncogenes on derived chromosomes get under
      control of the molecular enhancers of the IgH locus. This paper summarizes the
      current knowledge concerning the formation mechanism of chromosomal
      translocations in multiple myeloma and the areas of their formation; it also
      mentions the way of their detection. The paper presents the most frequent types
      of chromosomal translocations affecting the area of chromosome 14q32 in the
      karyotype of people diseased with multiple myeloma, including the frequency of
      their detection and the prognostic significance for the patients.

PMID- 19102213
TI  - [The preparation of myeloma-specific T cells activated with dendritic cells
      loaded with nonapeptides derived from mucin protein MUC1 and catalytic subunit of
      telomerase hTERT].
AB  - BACKGROUND: Multiple myeloma is an incurable hematological disease. High-dose
      chemotherapy including autologous stem cell transplantation is recently
      considered a standard therapy for myeloma. Unfortunately, a relapse of the
      disease is inevitable. Therefore, new approaches such as immunotherapy have been
      considered recently. A specific activation of cytotoxic T cells can be reached
      using dendritic cells loaded with tumor-specific antigens. The HLA-A2-specific
      nonapeptides as hTERT derived from catalytic subunit of telomerase and MUC1
      derived from mucin protein can be used. DESIGN AND SUBJECTS: Activation,
      identification, separation and expansion of myeloma-specific T cells from healthy
      HLA-A2 blood donors were tested in an in vitro study using hTERT and MUC1
      nonapeptides as tumor-specific antigens. METHODS AND RESULTS: T cells and
      dendritic cells were obtained from peripheral blood. T cells were repeatedly
      stimulated with hTERT and MUC1 nonapeptide-loaded dendritic cells. Activated
      myeloma-specific T cells produced interferon gamma and were evaluated by flow
      cytometry. The activated T cells were immunomagnetically separated and in vitro
      expanded to the number usable in clinical trials. CONCLUSIONS: This study
      demonstrates feasibility of a specific activation, identification, separation and
      expansion of tumor-specific T cells that can be used in myeloma therapy.

PMID- 19102214
TI  - [The role of PET in the diagnosis and prediction of the treatment response in
      patients with cervical carcinoma treated with radiotherapy--results of pilot
      study].
AB  - BACKGROUND: Positron emission tomography (PET) is used to distinguish between
      benign and malign tumours, to diagnose relapse or post-therapeutic changes and
      recentlyto predict treatment response. PET is also a complementary method to
      determine target volumes in radiotherapy. Using the PET in routine oncology
      practice can change disease management and improve treatment outcomes of cancer
      patients. We performed a pilot study to validate the role of PET in staging and
      in radiotherapy treatment planning of cervical carcinoma. PATIENTS AND METHODS:
      Between March 2005 and May 2007, 51 patients with cervical carcinoma were treated
      with combination of external beam radiotherapy and HDR brachytherapy, with or
      without concomitant cisplatin. The lymphatic nodes treatment field size was
      determined by PET/CT fusion. Treatment results were evaluated by PET 3 and 9
      months after completion of radiotherapy. RESULTS: The difference in the results
      of PET and CT was evaluated in this study. In 32 cases (62.75%) the results of
      initial PET and CT were identical, in 14 cases (27.45%) the nodal involvement was
      more extensive according to PET, in 5 cases (9.8%) the nodal involvement was more
      extensive according to CT. Comparing the results of PET done before and 3 months
      after the treatment, we found stable disease in 3 cases (5.88%), progression of
      disease in 4 cases (7.84%), partial regression in 3 cases (5.88 %) and in 35
      cases (68.63 %) both PET scans were negative. There should not occur any false
      positive results caused by inflammatory reaction persisting 3 months after
      radiotherapy, as was confirmed by repeating PET 9 months after the treatment.
      CONCLUSION: The results of this study confirmed the important role of PET in
      diagnosis and treatment of cervical carcinoma and for determination of target
      volumes in radiotherapy. The predictive value of PET has not yet been validated
      in our study. PET was integrated into the standard staging of cervical carcinoma
      in Masaryk Memorial Cancer Institute.

PMID- 19102215
TI  - [Breast cancer in puerperium].
AB  - AIM: This case study reports an occurence of a mammary gland carcinoma in woman
      during her pregnancy and puerperium. CASE REPORT: Patient was 29 years old woman,
      without any familiar or personal history of cancer or cancer risk factors. There
      was a finding of palpable resistance in the lateral superior quadrant of right
      breast in 30 week of gestation, which was considered to be hormonal changes in
      pregnancy. The third day after delivery a breast ultrasonography was performed
      because of persisting mastodynia, moderate oedema in described area and
      resistance nonresponding to the typical finding in period of incipient lactation.
      The result was suspicious of tumor. The core cut biopsy revealed invasive ductal
      carcinoma grade 3 and the staging was determinated as T4b N2 M1 (liver). Because
      of the high clinical stage of the disease, primary sugical therapy (modified
      radical mastectomy) was not indicated and the patient underwent neoadjuvant
      chemotherapy followed byradiotherapy. There was a control PET scan after the
      chemotherapy which confirmed only residual tumor in the area of affected breast
      and no viable tumor cells in the area of the liver. Additional reduction of the
      primary tumor lesion occured after the radiotherapy. The control examination 3
      months after the treatment found the statement of the relapse of disease. At the
      present time, 14 months after the delivery, the paliative chemotherapy is
      planned. CONCLUSION: Obstetricians should take care not only for routine
      examinations of pregnant women, but also of the breast changes and when there are
      uncertain, they must use appropriate diagnostic methods.

PMID- 19102217
TI  - [Carcinoids in the population of the Czech Republic].

PMID- 19102218
TI  - [Therapeutic approaches for breast carcinoma].
AB  - With increasing incidence of breast cancer its prevalence also increases.
      Improvement of therapeutic approaches recently introduced led to improved
      treatment outcomes. The introduction of taxanes into the adjuvant treatment
      prolongs the overall survival (OS) of the patients. Third generation of aromatase
      inhibitors appear better than tamoxifen in the adjuvant treatment of
      postmenopausal women. New anticancer drugs in combination with bevacizumab and
      trastuzumab have brought new possibilities in treatment of patients with
      metastatic breast cancer: their use apparently increases the rate of treatment
      response and overall survival.

PMID- 19102219
TI  - [Role of human papillomavirus in carcinogenesis of head and neck cancer].
AB  - Head and neck squamous cell carcinomas develop predominantly in individuals over
      40 years of age and more frequently in males. The strongest risk factors for this
      disease are long-term abuse of tobacco products and alcohol. Recently, several
      reports of increasing incidence of head and neck cancer in atypical population
      groups of females or young adults have been published, often in patients with no
      history of smoking or alcohol abuse. It seems highly probable that at least in a
      part of these cases, human papillomavirus (HPV) played an important etiological
      role. Some of the HPV types were proved to cause certain anogenital carcinomas,
      particularly cervical carcinoma. It seems that in some cases these very HPV types
      are also involved in head and neck carcinogenesis. Published data on the
      prevalence of HPV infection in head and neck squamous cell carcinomas vary in
      different studies. However, it is generally understood that the infection is more
      commonly present in carcinomas of the oropharynx and palatine tonsils than in
      oral cavity carcinomas. The hypothesis of sexual transmission of oncogenic HPV
      types has yet to be confirmed. It is not clear whether current HPV vaccines could
      possibly decrease the incidence of head and neck squamous carcinomas.

PMID- 19102220
TI  - [Utilization of MLPA to detection of genetic changes in neuroblastoma].
AB  - Neuroblastoma (NB) is a childhood cancer derived from neural crest cells, with a
      highly variable clinical course and biologic behavior. Several genomic imbalances
      correlate to prognosis in NB, with structural rearrangements, including MYCN
      amplification, in a near-diploid setting typically signifying high-risk tumours
      and numerical changes in a near-triploid setting signifying low-risk tumours. At
      present, many different techniques are used for detection of these copy number
      changes including standard chromosome karyotyping, comparative genomic
      hybridization (CGH), fluorescent in situ hybridization (FISH) and array CGH. Now,
      a new methodology called multiplex ligation dependent probe amplification (MLPA)
      has been developed. This new approach is based on polymerase chain reaction (PCR)
      amplification of ligated probes hybridized to target DNA sequences. MLPA is a
      highly sensitive, a rapid, accurate, reliable, and cost-effective. ENAQUA use
      neuroblastoma MLPA kit as a standard for detection genetic changes in
      neuroblastoma. We found high level concordance in FISH, CGH and MLPA
      investigations.

PMID- 19102221
TI  - [Immediate breast reconstruction and radiotherapy].
AB  - Immediate breast reconstruction has become widespread in breast cancer patients
      since the eighties of the last century. Now the criteria for adjuvant chest wall
      radiotherapy are changing as the problem of interference between reconstruction
      and radiotherapy appears. The irradiation of a reconstructed breast increases
      complication rate and worsens long-term cosmetic results. If radiotherapy is
      needed, it should be given regardless of reconstruction and delayed, instead
      immediate, breast reconstruction is preferable. However, the necessity of
      radiotherapy is rather difficult to predict before surgery as the criteria arise
      from the definitive histopathologic examination. Consequently, the former
      reconstruction enthusiasm has been moderated. Oncologists should be familiar with
      immediate reconstruction issues in order to provide their patients with realistic
      information and not hinder reduction of negative esthetic side effects of
      oncological treatment. A survey of the most important literature concerning this
      issue is presented in the article.

PMID- 19102222
TI  - [Monoclonal gammopathies of undetermined significance].
AB  - Monoclonal gammopathy of undetermined significance (MGUS) is the most common type
      of monoclonal gammopathies. Genetic changes, various cytokines and bone marrow
      angiogenesis play an important role in the pathogenesis. As far as the malignant
      transformation of MGUS is concerned, size and type of the serum M-protein, serum
      kappa and lambda free light chain ratio and number of plasma cells in peripheral
      blood seem to play a predictive role. A new possible risk-stratification model
      predicting progression of MGUS to multiple myeloma or other related disorders was
      presented in 2006. The model takes three parametres in consideration, type and
      initial size of the serum M-protein and serum kappa and lambda ratio. Patients
      are divided into four risk groups with different risk of progression, from 5% at
      20 years in low risk group to 58% in high risk group. The interval from MGUS
      diagnosis to the evolution of multiple myeloma or other related malignancies
      ranges from 1 to 30 years. Nevertheless, the risk of progression persists even
      after more than 30 years after MGUS diagnosis.

PMID- 19102223
TI  - [Results of the monitoring the group of patients treated for the Hodgkin disease
      in the period of 1971 to 1996. Part 2: fertility after therapy].
AB  - BACKGROUND: This authors team has been dealing with the Hodgkin disease problems
      since 1971. The MORHO study started at eight working places in 1978 according to
      unified diagnostic and medical protocol. The aim of this study is evaluation of
      influence of Hodgkin disease therapy on the fertility in young patients. PATIENTS
      AND METHODS: Group of patients treated for Hodgkin disease in years 1971-1996 at
      workplaces using the same treatment protocol has been analyzed and the results
      have been compared with results of other medical centers in the world. Some of
      the young patients in fertile age became parents after the treatment. RESULTS:
      Information of number of pregnancies and of children born, long term surveillance
      and complications of treatment has been collected and discussed. Many patients
      stayed fertile also after therapy of numerous relapses. There was 75 children
      born to 34 women and 11 men previously treated for Hodgkin disease. CONCLUSION:
      The results of our study are comparable with results of statistial evaluation of
      similar studies in the world cancer research centers.

PMID- 19102224
TI  - [Local recurrences after conservative surgery in breast carcinoma].
AB  - BACKGROUND: Local recurrences in breast after conservative surgery are failure of
      primary therapy. The aim of the study was monitoring of local recurrences after
      conservative surgery and also relationships of local recurrences with disease
      free interval and survival. MATERIALS AND METHODS: Between 1.12.1998 and
      30.06.2004, 143 patients with breast carcinoma were treated at Department of
      Surgery Atlas Hospital Zlin by conservative surgery. All patients received
      radiotherapy and boost in breast. Macroscopic free margins were 10 mm and
      reexcision were done in all patients with free margins less than 5 mm. Dose of
      the radiotherapy whole breast and cavity were 50 Gy, interval 5-6 weeks, daily
      2Gy. Brachytherapy received all patients, combination of chemotherapy and
      hormonal therapy were 56x, only chemotherapy 31x, only hormonal therapy 31x and
      without adjuvant therapy 25x. RESULTS: Median follow-up was 32 month. Tumor size
      according to TNM classification: TIS 10, pT1a 1x, pTb 28x, pTc 55x, pT2 44x, pT3
      5x. Stage: 0 1x, I 58x, IIA 56x, IIB 24x, IIIA 4x. Local recurrences in breast
      were 5x, (3.49%), distant metastases 6x, (4.1%) and 3x (2.09%) appeared distant
      metastases and death at breast carcinoma without local recurrence. Only in one
      patient local recurrence were followed by distant metastases and death. Interval
      from local recurrence and death was 12 month. Size of the original tumor with
      local recurrences was from 10mm to 45 mm. Interval from the time of initial
      treatment to local recurrences was from 12 to 42 month. Surgical treatment of
      local recurrences included mastectomy 4x and conservative surgery 1x. CONCLUSION:
      Number of local recurrences is in correspondence with international guideline and
      results of modern multimodal therapy.

PMID- 19102225
TI  - [Where and how do the cancer patients in the Czech Republic die? Some remarks on
      the need and availability of paliative care].

PMID- 19102226
TI  - [Myocardial biomechanics in patients with coronary circulatory insufficiency].
AB  - The paper analyzes a new approach to evaluating myocardial systolic and diastolic
      function, which is based on recording of the rate of myocardial displacement in
      different phases of a cardiac cycle. Changes in the rate of vector movements in a
      period of isovolumic contraction and relaxation are shown on ample clinical
      materials in both healthy individuals and patients with coronary heart disease.
      There is evidence for a significant difference in the performance of a stress
      test by healthy individuals and patients with a low coronary circulatory reserve.

PMID- 19102227
TI  - [Early activation of patients after myocardial revascularization under prolonged
      extracorporeal circulation].
AB  - The purpose of the study was to analyze the experience with fast-track activation
      of patients after myocardial revascularization with cardiopulmonary bypass (CPB)
      longer than 150 min and to study the efficiency of these procedures. The study
      included 64 ischemic patients (56 males and 8 females) aged 58.7+/-1 years,
      surged with CPB. In all cases, surgery and CPB were uncomplicated. The time of
      CPB was 151-298 (187+/-4) min; that of aortic cross-clamping was 67-181 (121+/-4)
      min. Hemodynamics, pulmonary gas exchange, and laboratory parameters were
      virtually normal before activation. Tracheal extubation was performed in the
      operating room 27-117 (61+/-3) min following the end procedure. The length of
      intensive care unit (ICU) stay was less than 24 hours in 82.8% of patients. The
      remaining patients stayed at an ICU 2-15 (2+/-1) days, which was associated with
      cardiac, pulmonary, renal complications, etc. The doses of dopamine and/or
      dobutamine and norepinephrine, and the index PO2a/FiO2 were shown to be
      predictors of ICU stay. It is concluded that fast-track activation is appropriate
      for patients undergoing prolonged CPB. The patients enrolled in the fast-track
      programme after prolonged CPB are to meet the following requirements: minimum
      inotropic and vasopressor support and PO2a/FiO2 greater than 350 mm Hg.

PMID- 19102228
TI  - [Optimization of the volemic status of cardiosurgical patients before initial
      anesthesia].
AB  - Twenty-six patients with coronary heart disease who had undergone aortocoronary
      bypass surgery were examined. In all the patients, central hemodynamic parameters
      were monitored by transpulmonary thermodilution. The patients were divided into 2
      groups. In Group 1 (n = 14), routine initial anesthesia was made without a
      preliminary volumetric loading test. In Group 2 (n = 12), a controlled volumetric
      loading test was carried out before induction; a decision on whether it might be
      made was taken on the basis of the results of a loading test for passive leg
      raise. The patients from both groups were hypovolemic at baseline, as suggested
      by the low values of central venous pressure (CVP) and global end-diastolic
      volume index (GEDVI). By the initiation of initial anesthesia, in Group 2 the
      mean blood pressure (BPmean), CVP, stroke index (SI), and GEDVI were
      significantly higher and total peripheral vascular resistance index (TPVRS) was
      significantly lower than in Group I (p < 0.05), as achieved via preliminary
      loading tests. After the maximum hypnotic effect being achieved in Group 1, there
      were reductions in BPmean, SI, GEDVI, dPmax, and TPVRS (p < 0.05). In Group 1,
      50% of the patients were observed to have hypotension episodes requiring the
      patient to be placed in Trendelenburg's position and to be given colloids as
      jets, and 3 patients received bolus vasopressors. After achieving the maximum
      hypnotic effect, BPmean, SI, GEDVI, and dPmax also decreased in Group 2 patients
      (p < 0.05). However, due to preliminary loading tests, these variables remained
      to be in the normal ranges and were significantly higher than in Group 1 (p <
      0.05). IOPSS objectively reflects the preload status at all stages of initial
      anesthesia and the leg raising test enables prediction of a cardiovascular
      response to a volumetric load. When infusion therapy is performed, it is
      advisable to take into account a relationship between altered preload (GEDVI) and
      cardiac performance (SI). This volumetric loading testing tactics before
      induction promotes GEDVI to be maintained in the normal ranges throughout the
      initial anesthesia and minimizes hemodynamic disorders at this stage.

PMID- 19102229
TI  - [Intraoperative evaluation of the microcirculatory system in cardiosurgical
      patients].
AB  - The investigation was undertaken to study the specific features of vessels of the
      microcirculatory bed in cardiosurgical patients during myocardial
      revascularization. The study covered 20 patients with NYHA Functional Classes III
      IV coronary heart disease. Ten patients from Group 1 were operated on the working
      heart (aortocoronary bypass surgery (ACBS) without extracorporeal circulation
      (EC)). In 10 patients from Group 2, myocardial revascularization was performed
      under normothermal (tcenter = 36 degrees C) EC (ACBS + EC). Microcirculatory
      blood flow was analyzed by laser Doppler fluometry. Microcirculatory blood flow
      index, variation coefficient, neurogenic and myogenic microvascular tone indices,
      and bypass value were estimated. It has been concluded that 1) laser Doppler
      fluometry evaluates the microcirculatory bed during anesthesia in cardiosurgical
      patients; 2) a dynamic response of the microcirculatory bed to stresses is
      retained during general anesthesia; 3) under normothermal EC, there are more
      pronounced microcirculatory disorders than during myocardial revascularization on
      the working heart.

PMID- 19102230
TI  - [Ways of reducing donor blood components during reconstructive surgery of the
      heart valves under extracorporeal circulation].
AB  - Blood loss and transfusion tactics were analyzed in 131 patients who had
      undergone correction of one, two, and three cardiac valves under general balanced
      anesthesia and extracorporeal circulation. The volume of intraoperative blood
      loss was 869+/-298 ml with the range of 700 to 2000 ml. Packed red cells (PRC)
      were transfused to 9% of patients; fresh frozen plasma (FFP) in 10%, PRC and FFP
      were transfused to 17% patients. Donor blood was not used in 63.5% of patients in
      order to save the patient's blood. It comprised the preoperative storage of
      autologous plasma in a quantity of 300-700 ml, the modified intraoperative
      reservation of autologous blood in a volume of 400-1200 ml, and, in 70% of
      patients, the use of washed autologous red blood cells. The hemostasis protocol
      included the use of epsilon-aminocapronic acid, aprotinin (trasilol) not more
      than 2,000,000 KUE, and packed platelets. For adequate heparin neutralization,
      after administration of the calculated dose of protamine, it was long
      administered in a dose of 25 mg/hour for 4-5 hours. The developed and introduced
      comprehensive program for the patient's blood maintenance and blood loss
      diminution made it possible to avoid transfusing PRC and FFP in more than 60% of
      patients with a blood loss volume of as high as 1500 ml; and to maintain adequate
      oxygen balance and hemostasis in the remaining patients.

PMID- 19102231
TI  - [Effect of perfusion volume of the Custodiol solution on the efficiency of
      cardioplegia in experiment].
AB  - The purpose of the present study was to compare the efficiency of small and
      standard volumes (1.5-20 and 7-10 ml/g of the myocardium, respectively) of
      Custodiol solution in myocardial ischemia lasting 2 and 4 hours. Experiments were
      carried out on 24 mongrel dogs weighing 22-36 kg under extracorporeal circulation
      (EC) with bicaval cannulation under moderate general hypothermia and balanced
      general intravenous anesthesia. According to the solution volume and cardioplegia
      (CP) duration, all the animals were divided into 4 groups: 1) 2-hour CP (standard
      volume); 2) 2-hour CP (small volume); 3) 4-hour CP (standard volume); 4) 4-hour
      CP (small volume); of them Groups 1 and 3 served as a control. Antegrade CP was
      accomplished by the conventional procedure. In Groups 1 and 3, the volume of
      Custodiol solution was 1000-2000 ml; in Groups 2 and 4, that was 300-600 ml
      depending on myocardial mass. In Groups 1 and 3, the mean duration of myocardial
      perfusion was 9.8+/-2.8 and 8.4+/-1.4 min, respectively; and in Groups 2 and 4,
      that was 4.2+/-0.7 and 4.5+/-1.4 min. Groups 3 and 4 animals received additional
      myocardial perfusion with Custodiol solution in a volume of 400-500 and 200-250
      ml, respectively. The efficiency of myocardial protection was evaluated from the
      course of a reperfusion period (RP) and from central hemodynamic changes, the
      concentrations of glucose, lactate, malonic dialdehyde, medium-weight molecules,
      and blood gas and electrolyte composition of the coronary sinus. The studies were
      performed in stages: outcome, launch of blood flow (5-10 in); RP (30 min);
      complete loading (30 min); disconnection from an extracorporeal circulation
      apparatus. The experiment has indicated that the use of Custodiol solution in the
      standard volumes ensures an effective cardioplegic protection within 4 hours.
      Reductions in the volume and time of perfusion to the values characteristic of
      extracellular-type solutions cause a lower efficiency of this protection.
      Moreover, myocardial damage progresses as the duration of CP increases. The used
      Custodiol solution dose of 1.5-2.0 ml/g of the myocardium is apparent to be
      insufficient to set an ionic balance between cardioplegic solution and
      intracellular fluid, which reduces the duration of CP effect and the efficiency
      of myocardial protection. It may be assumed that lower perfusion volume lowers
      the efficiency of the buffer system of the solution and the metabolic effects of
      substrates. The authors consider that the decreased volume and time of perfusion
      of intracellular Custodial solution are unjustified and may result in the
      development of complications associated with inadequate cardioplegic myocardial
      protection.

PMID- 19102232
TI  - [Respiratory provision of reconstructive operations for extended and multifocal
      tracheal stenosis].
AB  - The paper describes new approaches to anesthetic maintenance of reconstructive
      operations for multifocal and extended tracheal stenoses. The authors state a
      pathophysiological concept of and guidelines for respiratory approaches ensuring
      effective gas exchange and adequate hemodynamics at stages of various plastic
      repairs. Specifically, they describe the specific features of respiratory
      provision of rare surgical interventions: two-level tracheal resection and
      reconstruction and thyrotracheal complex transplantation in subtotal tracheal
      lesion. The advantages of high-frequency jet artificial ventilation using a
      Mansoon apparatus (Acutronic Medical Systems AG, Switzerland) are given.

PMID- 19102233
TI  - [Efficacy and safety of sevoflurane in various anesthesia modes (according to the
      results of a multicenter study)].
AB  - The paper presents the results of the limited multicenter sevoflurane study
      initiated by Abbott Lab, which was conducted in 2006. The study was undertaken to
      examine the efficacy and safety of sevoflurane in various anesthesia modes in
      patients (ASA I-III) with surgical diseases during surgical interventions into
      abdominal and thoracic organs and lower extremities. The study covered 96
      patients. The analysis indicates that the use of sevoflurane for mask induction
      and anesthetic maintenance is possible and safe for patients with ASA I-III.

PMID- 19102234
TI  - [Possibilities of estimating the depth of myorelaxation by a frontal
      electromyogram].
AB  - The authors studied the changes occurring in a frontal electromyogram (fEMG)
      recorded by commercial anesthesia depth monitors (Alaris AEP Monitor/2, Aspect A
      2000 XP, and CSM 2) as a criterion for evaluating the reduction of a
      neuromuscular block. Two hundred and two patients who had undergone various
      abdominal and colorectal interventions under total intravenous anesthesia (TIVA)
      or combined balanced anesthesia using volatile anesthetics were examined. The
      findings allow a preliminary conclusion that fEMG shows a moderate diagnostic
      accuracy in predicting relaxation release particularly under TIVA. fEMG is as a
      useful complement to clinical criteria for myoplegia management, but it is not an
      alternative to traditional accelerometry.

PMID- 19102235
TI  - [Anesthesia in mini-invasive (laparoscopic) surgery from a quality management
      perspective].

PMID- 19102236
TI  - [A laryngeal mask as an instrument of ventilation support during regional
      anesthesia].
AB  - When the duration of limb segment replantation is more than 8-10 hours under
      nerve block anesthesia, prominent are the factors of the patient's lassitude and
      fatigue caused by position discomfort, the elimination of which and the
      possibility of uncontrolled motor activity of the patient require deep sedation
      or his/her unconsciousness. In this connection, a laryngeal mask (LM) has proven
      to be a convenient and reliable alternative to an endotracheal tube, which allows
      tracheal intubation to be avoided in most cases. Our clinical observations of the
      course of anesthesia in patients during carpal segment replantations of 14 hours
      or more in duration have demonstrated that the LM reliably ensures upper airways
      patency, adequate ventilation, and gas exchange throughout the surgery. An
      algorithm of switching patients to different assisted ventilation modes to
      rapidly restore adequate ventilation and gas exchange if drug-induced respiratory
      distress occurs during regional anesthesia has been tested during 120 emergency
      and elective anesthesias. Indications for the clinical use of a LM in patients
      who need emergency reparative operations using microsurgical techniques are
      warranted. Various actions of an anesthesiologist are proposed while using a LM
      in patients with limb segment replantation.

PMID- 19102237
TI  - [Central hemodynamics under conditions of combined anesthesia on the basis of a
      thoracic epidural block].
AB  - The authors set themselves a task of assessing systemic hemodynamic parameters
      under combined general anesthesia on the basis of a thoracic epidural block (TEB)
      versus combined general anesthesia during thoracoabdominal interventions. Thirty
      patients were examined. Their physical status was in ASA Class II-IV. The
      preoperative examination was as follows: electrocardiography (ECG) (at rest), ECG
      (during exercise), and 24-hour ECG monitoring. Hemodynamic parameters, such as
      systolic blood pressure (BP), diastolic BP, mean BP, and heart rate), were
      intraoperatively measured by invasive and noninvasive techniques. By using the
      measurements of cardiac output (extrasternal Doppler study), the authors
      calculated cardiac index, specific peripheral vascular resistance (SPVS), and
      stroke index (SI). They made 24-hour ECG monitoring intra- and postoperatively
      (on days 1 and 5, respectively). The findings suggest that inclusion of TEB in a
      complex of anesthetic maintenance of thoracoabdominal operations along with
      combined or total intravenous anesthesia shows better hemodynamic changes, as
      indicated by a 31% increase in SI and a 32.6% decrease in double product with the
      stable values of mean BP and heart rate, which was not noted in the control
      group. The dose of narcotic analgesics was decreased by 2.6 times.

PMID- 19102238
TI  - [Does high thoracic epidural anesthesia affect the results of myocardial
      revascularization?].

PMID- 19102239
TI  - [A method for assessing analgesia--nociceptive evoked potentials: the first
      clinical cases].
AB  - The paper describes a new method for assessing analgesia, which is based on the
      use of a Caube-type electrode. It provides evidence that, unlike stimulation with
      the standard electrode for somatosensory evoked potentials, Caube-type electrode
      stimulation may cause late (long-latent) potentials in healthy volunteers,
      showing the fundamental capacity of selective nociceptor excitation. By using two
      cases with the pronounced pain syndrome, the authors show changes in nociceptive
      evokes potentials during epidural analgesia.

PMID- 19102240
TI  - [Psychoemotional comfort--is it a special component of anesthesia?].
AB  - The paper provides a rationale for using a special component of balanced
      multicomponent anesthesia based on regional blocks. Based on their own data and
      the analysis of the data available in the literature, the authors describe the
      etiology and pathogenesis of psychoemotional discomfort. Particular emphasis is
      placed on the causes and mechanisms of psychoemotional disorders and the
      patients' long positioning on a operating table. Based on the detected
      pathogenetic mechanisms, the authors show possible ways of achieving the
      patients' psychoemotional comfort under regional anesthesia--from premedication
      and various sedation modes to the monitoring of psychoemotional reactions.

PMID- 19102242
TI  - [Cervicogenic headaches: aspects of diagnosis and analgesia].
AB  - Eighty-six patients with cervicogenic headaches underwent a comprehensive
      clinical and instrumental studies involving neurological and neuroorthopedic
      examinations; pain rating by the visual-analogue scale (VAS) and the rank scale,
      and neuroimaging and electrophysiologic techniques. The patients were divided
      into two groups: a study group (n = 43) and a control one (n = 43). In the study
      group, treatment policy was determined by the intensity and duration of the pain
      syndrome: local anesthetic blocks of the occipital nerve, facet joints, and the
      trigger points of the cervicocranial area were used to arrest acute pain of a VAS
      score of 5 or more. With a pain syndrome score of less than 5, treatment was
      initiated with reflex exposures. All the patients from the study group took
      nonsteroidal anti-inflammatory drugs (NSAID) and, if required, central
      myorelaxants. The control group received the conventional therapy, including drug
      (NSAID, central myorelaxants, and anticonvulsants) and non-drug (physiotherapy
      and massage) ones. Medicinal blocks and reflex analgesia could relieve the pain
      syndrome in cervicogenic headaches in shorter periods and reduce the dosage of
      the drugs used in the study group patients as compared with the controls.

PMID- 19102241
TI  - [Use of anesthesiological technologies in the complex treatment of cervicocranial
      pain syndromes].
AB  - Four hundred and eighty-four patients with pain syndromes of cervicocranial
      localization, such as migraine, exercise-induced headache, cervicogenic headache,
      trigeminal neuralgia, trigeminal neuropathy, and occipital neuralgia were
      observed. The patients were randomized by the type, intensity, and duration of
      the pain syndrome and subdivided into two subgroups in each of the study
      nosological entities. The patients from control groups received the conventional
      complex therapy including drug (nonsteroidal anti-inflammatory drugs, central
      myorelaxants, anticonvulsants, and antidepressants depending on the type of a
      pain syndrome) and non-drug (physiotherapy, massage, and therapeutic exercises)
      ones. The patients were examined before, during, and after a course of therapy
      and comprised neurological and neuroorthopedic examinations; pain rating by the
      visual-analogue and the rank scale, and neuroimaging and electrophysiologic
      techniques. Comparison of the results obtained in the respective subgroups has
      indicated that anesthetic modes and reflex exposures in the complex therapy is an
      effective and safe procedure for relieving pain in the head and neck. Medicinal
      blocks arrest pain at shorter notice, reduce the single and daily doses of the
      used drugs and, in some cases, avoid their administration, thus, preventing their
      side effects, improve the quality of life, and increase the social activity of
      patients with cervicocranial pain syndromes.

PMID- 19102243
TI  - [Multimodal approach to postoperative analgesia in patients with neuropathic
      pain].
AB  - Chronic neuropathic pain syndrome observed prior to surgery not only influences
      the intensity of pain, but also reduces the efficiency of selective use of
      analgesics. The purpose of the investigation was to study the efficiency of
      various analgesics and their combinations after lumbar microdiskectomy. Seventy
      six patients who had undergone lumbar microdiskectomy and who suffered from
      chronic back pain were examined. According to the mode of postoperative
      analgesia, the patients were divided into 4 groups: 1) 20 patients received i. m.
      promedol 20 mg (a control group); 2) 20 had i. v. tramal (patient-controlled
      anesthesia); 3) 18 were given i. v. xefocam 24 mg/day; 4) 18 i. v. ketamine 0.1
      mg/kg/hour + i. v. xefocam 24 mg/day. Their analgesic effect was evaluated using
      a visual analogue scale 1, 2, 4, 6, and 24 hours after surgery. The use of
      xefocam in combination with microdose ketamine was ascertained to cause no
      increase in the frequency of adverse reactions, to upgrade the quality of
      analgesia, and to minimize the intensity of pain 24 hours following surgery.

PMID- 19102244
TI  - [Xenon in anesthesiology: merits, shortcomings, reality, and perspectives].

PMID- 19102245
TI  - [Anesthetic maintenance of visceral transplantation in the university clinic,
      Indiana, USA: results of a scientific-and-practical trip].

PMID- 19102246
TI  - [Research of morphogenesis and regeneration and Orenburg scientific histological
      school founded by F.M. Lazarenko (from 1930s to the beginning of XXI century)].
AB  - This paper reviews the basic results of the scientific investigations of Orenburg
      scientific histological school which was founded by Prof. F.M. Lazarenko, on the
      problems of morphogenesis and regeneration, starting from the thirties of XX
      century till present time. The contribution of F.M. Lazarenko, Z.S. Khlystova,
      A.A. Stadnikov and other Orenburg scientists to the development of the problems
      of morphogenesis and regeneration is demonstrated.

PMID- 19102247
TI  - [Hypothalamic nonapeptidergic control of cell and tissue homeostasis, pro- and
      eukaryotes interactions].
AB  - The data on the structural and functional organization of mammalian hypothalamic
      nonapeptidergic neurosecretory system and its role in the control of the animal
      adaptive reactions, are presented. New findings demonstrating the biologic
      regularities of pro- and eukaryote interactions in situ as well as in culture and
      in experimental pathology, are summarized. On the basis of modem morphological
      approaches, significant morphofunctional criteria are established, which permit
      to efficiently evaluate the range of histoblastic and organotypic potentialities
      of the visceral organs and their compensatory-adaptive properties, realized under
      the hypothalamic neroendocrine control and observed during the interactions with
      bacterial pathogens. The important place is given to experimental histological
      substantiation of the new methods of complex treatment of the wounds and pyo
      necrotic processes, including those employing hypothalamic nonapeptides
      (oxytocin).

PMID- 19102248
TI  - [The role of structural changes of the endothelium and myocardium in the
      development of experimental heart failure].
AB  - The aim of the investigation was to study the role of structural myocardial and
      endothelial reorganization during the experimental heart failure (doxorubicin
      model). Rat endocardial and aortal endothelium as well as left ventricular
      myocardium, were studied using the methods of light and electron microscopy and
      immunocytochemistry (TUNEL-assay). The major regularities of structural and
      functional myocardial and endothelial reorganization were determined in rats with
      an experimental heart failure. The pronounced cardiomyocyte (CMC) heteromorphism
      was found. CMCs with the signs of hypertrophy and hyperplasia were identified
      together with the CMCs showing discomplexation of sarcomeres and fragmentation of
      myofibrils, CMCs with the numerous caveolae, liposomes, autophagosomes and myelin
      like bodies. The peculiarities of the ultrastructural changes were established in
      the endocardial and aortal endothelium. The increase in CMC and endothelial cell
      number showing the signs of apoptosis, was demonstrated. The role of structural
      and functional myocardial and endothelial reorganization during experimental
      heart failure is discussed.

PMID- 19102249
TI  - [Morphological analysis of intestinal wound and interintestinal anastomosis
      healing after the application of microsurgical techniques under the experimental
      conditions].
AB  - This paper presents the data of the morphological analysis of the healing of
      small intestine wounds as well as colon wounds and anastomoses created using the
      microsurgical operative techniques. The possibility of application and the
      efficacy of microsurgical technique was shown for the suturing of small intestine
      wounds during stage I and II peritonitis and large intestine anastomoses during
      the colonic passage disturbances with the epithelization by day 7. The
      significance of colon wall microanatomical peculiarities for the application of
      the microsurgical technique was determined. The possibility of wound and
      intestinal colonic anastomosis healing according to the primary type during the
      period of 4-6 days without the dense connective tissue scar formation is proved.

PMID- 19102250
TI  - [Regenerative potentialities of pancreatic tissues in experimental infectious
      pancreonecrosis].
AB  - The repair processes in the pancreas in infected pancreonecrosis after oxytocin
      (OT) administration were studied in 120 male rats with the body mass of 280-310
      g, using light microscopy, histochemistry, electron microscopy and
      immunocytochemistry (p53 protein detection). Pancreonecrosis was induced by
      microtraumatizing the pancreatic lobules with bile injection and Staphylococcus
      aureus suspension infusion. During days 3-14, the intensifying processes of
      ischemia, acinar and ductal lysis, pancreatocyte dystrophy and death were
      observed in experimental animals. In paranecrotic areas, acinar discomplexation
      was found together with the signs of increased secretory activiry in
      pancreatocytes. Pancreatic tissues were infiltrated with erythrocytes,
      granulocytes, lymphocytes and macrophages which were actively engaged in
      phagocytosis. OT was found to create the conditions necessary for adequate
      realization of the regenerative properties of pancreatocytes, microvessels, cells
      of fibroblastic line, and macrophages with a concomitant decrease of apoptotic
      dominant in cellular elements.

PMID- 19102251
TI  - [Changes in the respiratory tract epithelium of the rats infected after the
      exposure to a prolonged emotional-painful stress: effect of oxytocin].
AB  - Effect of oxytocin on the respiratory tract epithelium of rats infected with
      Escherichia coli following the prolonged emotional-painful stress, was studied
      using the methods of histochemistry, immunocytochemistry, light and electron
      microscopy. It was found, that prolonged stress caused the exertion of protective
      adaptive capacities of the epithelium, while the administration of an antigen
      resulted in the failure of adaptational mechanisms. Oxytocin was found to
      participate in the formation of the response of the epithelial secretory cells to
      stressful influences by activating their protective functions. It stimulated and
      supported the protein-synthetic (CC16 protein production by Clara cells) and
      mucin-producing (goblet cells) functions of secretory cells, thus stabilizing the
      protective epithelial mechanisms under the conditions of intense functioning.

PMID- 19102252
TI  - [Morpho-functional characteristics of the bronchiolar exocrinocytes (Clara cells)
      in adults].
AB  - Using the methods of immunocytochemistry, light, electron microscopy, and
      morphometry, localization and the structural and functional characteristics of
      bronchiolar exocrinocytes (Clara cells - CC) in human bronchiolar epithelium were
      studied during the mature age period of ontogenesis. CC were detected in both
      terminal and respiratory bronchioles, while their number was greater in the
      latter. With the increasing age within this period of human ontogenesis, the
      number of CC decreased. The quantitative decline of their number with age was
      found to depend on the duration of smoking. The smoking experience equivalent to
      10 pack-years was defined as a critical one, as despite the absence of
      radiological manifestations of pulmonary pathology and the optimal results of the
      pulmonary function tests, in patients with this or greater smoking experience,
      the minimal fibrosis was detected, which could be demonstrated at both light and
      electron microscopical levels. This could be related with the decrease in CC
      number, since their secretory product was found to inhibit the activity of
      fibroblast chemotaxis.

PMID- 19102253
TI  - [Topographic anatomy of human thoracic organs in the early fetal period].
AB  - The purpose of the present investigation was to evaluate the holotopy,
      skeletotopy and sintopy of human heart, trachea and esophagus in the early fetal
      period. The quantitative evaluation of the topography of these organs was given
      as a result of study of 100 human fetuses aged 16-24 week with the modification
      of N.I. Pirogov method and using the multiplane histotopographical sections in
      the multidimensional coordinate system. The horizontal sections were selected,
      that could be proposed as the standard ones. he results of this investigation may
      be recommended for the improvement of the ultrasonographic and magnetic resonance
      tomographic diagnosis and fetal surgery development.

PMID- 19102254
TI  - [Morpho-functional characteristics of reproductive organs of rodents from the
      area affected by a plant, processing gas with the increased content of sulfur
      compounds].
AB  - The biology of reproduction of 5 rodent species--small gopher (Spermophilus
      pygmaeus Pallas, 1778), reddish gopher (Spermophilus major Pallas, 1779), sasin
      lemmer (Lagurus lagurus Pallas,1773), forest mouse (Apodemus sylvaticus Linnaeus)
      and bank vole(Clethrionomys glareolus Schreber, 1780)--inhabiting the sanitary
      protective zone of the gas processing plant, was investigated with the use of
      histological, electron microscopical, immunocytochemical and morphometric
      methods. Intensification of the reproduction (growth of female fecundity,
      reduction of the puberty age) in some species (forest mouse) compensated for the
      negative changes in the reproduction, which resulted from the influence of the
      industrial factors (premature loss of ovarian follicular reserve, accelerated
      embryonic death rate, increased destructive changes in the gonads) and provided
      for the preservation of the population sizes. The intense functioning of
      reproductive organs in the other species (small and reddish gophers) was
      insufficient to compensate for the damage inflicted by the man-caused actions.

PMID- 19102255
TI  - [Application of modern methods of intravital visualization for the study of
      various body parts: clinical anatomy].
AB  - This paper reviews the methodological and technical possibilities of the
      application of modern imaging methods (ultrasonography, computer tomography and
      its variety spiral computer tomography, magnetic resonance tomography, endoscopic
      investigation) for the study of intravital anatomy of body regions, inner organs,
      their structures and cavities. It is shown that these methods provide the
      objective information on the position, dimensions, and structure of the objects
      under study Using the morphometric methods with further variation-statistical
      analysis gives the objective quantitative characteristics, allows to distinguish
      marginal and most common variants of form and dimensions of anatomical
      structures.

PMID- 19102256
TI  - [Classification and treatment of thoracolumbar fractures].

PMID- 19102258
TI  - [Percutaneous vertebroplasty for the treatment of acute burst thoracolumbar
      fractures].
AB  - OBJECTIVE: To explore the feasibility of percutaneous vertebroplasty for the
      treatment of acute burst thoracolumbar fracture. METHODS: Fifty-eight patients
      (male 38 and female 20, ranging in age from 38 to 70 years, with an average of
      56.8 years) with acute burst thoracolumbar fracture were treated by percutaneous
      vertebroplasty. The injuried vertebrae were T11 in 3 cases, T12 18 cases, L1 29
      cases, L2 5 cases and L3 3 cases. All suited cases were classified into 3 types
      according to injuried vertebral shapes,type I (safe type 26 cases), type II (risk
      type 21 cases), and type III (marginal type 11 cases). RESULTS: All the patients
      were followed up ranging from 1 to 2.5 years (mean 1.6 years). Fifty-three
      patients could walk in 1 to 3 days after operation. Among 55 patients who
      obtained complete recovery (CR), 39 patients could do daily works and 16 patients
      could do houseworks. The CR rate was 95%. Three patients who obtained partial
      recovery (PR), could live by themselves and felt slight lumbago after movements.
      The PR rate was 5%. CONCLUSION: Percutaneous vertebroplasty for the treatment of
      acute burst thoracolumbar fracture is a feasible and effective method even for
      particular risks.

PMID- 19102257
TI  - [Evaluation of percutaneous vertebroplasty of 190 cases].
AB  - OBJECTIVE: To evaluate the therapeutic effect of percutaneous vertebroplasty
      (PVP) guided by X-ray fluoroscopy in treating osteoporotic spinal compression
      fractures, hemangioma of vertebra and metastatic carcinoma of vertebra. METHODS:
      One hundred and ninety patients with 275 diseased vertebra underwent PVP under
      the guidance of C-arm fluoroscopy (male 80, female 110, ranging in age from 53 to
      91 years, with an average of 66 years). Bone marrow biopsy needle was inserted
      percutaneously via transpedicular way into the diseased vertebra.
      Polymethylmethacrylate (PMMA) was then injected into the diseased vertebra.
      Visual analogue scale (VAS), mobility and analgesic usage were evaluated pre
      operation and 3 months after PVP. RESULTS: PVP was successful in 190 cases (275
      vertebrae). VAS was tested by t test at 3 months after PVP (P < 0.05).
      Simultaneously, scale of patient's mobility and scale of analgesic usage was
      tested by rank sum test at 3 months after PVP (P < 0.05). CONCLUSION: As the
      mimimally invasive operation, PVP can alleviate pain in early time, avoid kinds
      of complications by shortening the patient's time in bed and have the
      characteristic of simply operative procedure and low expenses. It is an effective
      mini-invasive technique for osteoporotic spinal compression fractures, hemangioma
      of vertebra and metastatic carcinoma of vertebra.

PMID- 19102259
TI  - [Anterior decompression and reconstruction for the treatment of burst
      thoracolumbar fractures with anterior and median column injury].
AB  - OBJECTIVE: To explore the treatment of anterior decompression and reconstruction
      for burst thoracolumbar fractures with anterior and median column injury and to
      evaluate the therapeutic effect. METHODS: Thirty-four patients suffering from
      burst thoracolumbar fractures with anterior and median column injury (male 22 and
      female 12, aged from 20 to 63,with an average of 40.5 years) were treated by
      anterior decompression and reconstruction from May 2001 to October 2006.
      Operative duration, bleeding and the neurological function of patients were
      recorded. RESULTS: All the patients were followed up from 3 to 60 months and the
      average time was 24.5 months. Operative duration was (178 +/- 65) min. The volume
      of bleeding was (1 750 +/- 950) ml and the volume of autotransfusion was (950 +/-
      750) ml. Cobb angle were corrected from 27.0 degrees +/- 6.5 degrees to 3.0
      degrees +/- 1.5 degrees. All fractures obtained fusion. No failure of internal
      fixation and formation of false joint happened. CONCLUSION: The technique of
      anterior decompression and reconstruction for burst thoracolumbar fractures with
      anterior and median column injury is effective, with which the decompression and
      reconstruction of the spinal stability can be performed under direct vision at
      one stage, and the sagittal alignment can be corrected at the same time. The
      procedure will be more smoothly by the application of the intraoperative
      autotransfusion.

PMID- 19102260
TI  - [Surgical treatment of type-C thoracolumbar fractures].
AB  - OBJECTIVE: To explore the operative approach and method of internal fixation for
      the treatment of type-C thoracolumbar fractures. METHODS: T wenty-eight patients
      (male 20, female 8, ranging in age from 20 to 54 years, with an average of 38.5
      years) with type-C thoracolumbar fractures were invovled in the study.
      Distributed segments involved T11 in 2 patients, T12 in 3 patients, L1 in 11
      patients, L2 in 8 patient, L3 in 3 patients and L4 in 1 patient. Twenty-six
      patients were followed up (range from 12 to 20 months). According to the analysis
      of X-ray and CT image,height of vertebral body, Cobb angle on sagittal and
      coronal plane and the percentage of occupancy of vertebral canal were measured.
      The recovery of nerve, happening of back pain and the failure of internal
      fixation were observed. RESULTS: The preoperative averaging height-loss decreased
      from 37.4% to 6.8% and the deformation of coronal plane was completely rectified.
      The preoperative averaging Cobb angle on sagittal plane recovered from 22.3
      degrees to 5.6 degrees and the preoperative occupancy of vertebral canal
      averaging recovered from 33.7% to 5.9%. The difference was statistically
      significant (P < 0.05). Moreover, after 1 year follow-up, the changes of the
      above-mentioned index was no statistically significant (P > 0.05). Except for 8
      patients with complete nerve damage losing the possibility of recovery, the
      others with incomplete nerve damage obtained 1 to 3 degree's improvement. The
      ratio of back pain occurrence was 19.2%. There was no failure of internal
      fixation. CONCLUSION: The treatment of thoracolumbar type-C fractures with simple
      posterior long-segment internal fixation or posterior long-segmental fixation
      added by anterior autograft fusion is a reliable and effective method. The short
      term therapeutic effect is satisfactory and the long-term therapeutic effect is
      to be further observed.

PMID- 19102261
TI  - [Clinical meaning of the surrounding compression on the nerve root by the
      protruded nucleus pulposus and facet or lamina (ligamentum flavum): analysis of
      CT (MRI) axial slice images of 71 patients with lumbar disc herniation].
AB  - OBJECTIVE: To observe the pinching action to the nerve root by the lumbar disc
      herniation and facet or lamina (ligamentum flavum) and evaluate its clinical
      meaning. METHODS: Seventy-one patients were divided into 3 groups according to
      the size of distance between protrusion of nuclear and facet or lamina
      (ligamentum flavum). The degree of the straight leg raising of the affected side
      (SLR) and the sagittal index (SI) of lumbar disk herniation were measured and
      analyzed among them. RESULTS: There was no corelation between the affected degree
      of SLR and sex, age and SI of patient (P > 0.05). The coefficient between
      distance group and the affected degree of SLR is-0.878 7 (P < 0.01). CONCLUSION:
      The degree of the surrounding compression by the protrusion of nuclear and facet
      or lamina (ligamentum flavum) reflects the injuried severity of the nerve root.

PMID- 19102262
TI  - [Autologous free fibula with periosteum transplantation for the treatment of bone
      defects of the ulna and radius].

PMID- 19102263
TI  - [Application of lumbar discography in the diagnosis and treatment of the
      discogenic lumbodynias].
AB  - OBJECTIVE: To explore the diagnostic value of lumbar disc imagery applied for
      patients with discogenic lumbodynias and the outcome of lumbar fusion and the
      significance of the imagery technique in choosing the joints and sections for
      fusion. METHODS: The lumbar imagery technique was applied for 35 patients who
      suffered from discogenic lumbodynias, involving 74 discs. All the cases got MRI
      and CT scanning. The results of the imagery and MRI were observed and induced
      pains were recorded. According to the imagery results, 20 out of the 35 patients
      received lumbar fusion and were followed up. RESULTS: Among 35 patients, the
      induced pains occurred at 22 discs in 20 patients (57.1%). All the 22 segments in
      20 patients with positive reaction were given lumbar fusion. The follow-up time
      was 10 months to 2 years with an average of 15 months. Based on the renewed
      MacNab standard, the results were excellent in 13 cases,good in 4 cases, fair in
      2 cases, bad in 1 case. Fifteen patients with negative reaction were given
      conservative treatment and pains disappeared completely in 5 patients,
      disappeared nearly in 7 patients, no changes or became worse in 3 patients. Six
      patients including 9 lumbar discs neighboring the fusion segments who were found
      no changes in MRI scan and no induced pains in lumbar discography, were not given
      fusion treatment. Meantime, 1 patient was given fusion treatment because his
      neighboring symptom-free discs getting more deteriorative resulted in the happen
      of serious symptoms. CONCLUSION: Lumbar imagery technique has its unique value in
      the diagnosis and selective treatment of lumbar-disc-related pains. Lumbar fusion
      of the intervertebral space causing pains can eliminate the suffering of
      patients. It is appropriate to select those deteriorating discs with symptoms in
      deciding the fusion segments.

PMID- 19102264
TI  - [Pilot study on the standardization of non-operative treatment of lumbar disc
      herniation].
AB  - Lumbar disc herniation (LDH) is one of the most common causes of sciatica. Many
      non-operative treatment strategies have acquired satisfied effects and have been
      recommended in many countries. The effectiveness and advantages of non-operative
      treatment may depend on how they are being used. Based on analysis of the current
      clinical condition,the positive attitude to the treatment of both patients and
      doctors, appropriate therapeutic scheme and sufficient time, as well as the
      systematically combined optimum procedure in stepladder-like ways may be feasible
      principles for the treatment of LDH.

PMID- 19102265
TI  - [Operative strategy of atlantoaxial instability].
AB  - OBJECTIVE: To evaluate the operative strategy and therapeutic outcomes of the
      atlantoaxial instability. METHODS: Clinical data of 29 patients with atlantoaxial
      instability were retrospectively analyzed. There were 27 males and 2 females. The
      mean age was 33 years old with a range from 18 to 54 years. There were fracture
      of anterior arch of atlas accompanied with ligamentum transversum rupture in 5
      cases, odontiod fracture in 7 cases, Hangman fracture in 6 cases, dysplasia of
      atlas and axis in 10 cases, ankylosing spondylitis in 1 case. The clinical and
      imaging manifestation of atlantoaxial instability were found in all patients. The
      symptoms and physical signs of superior cervical spinal cord disease or cervical
      spinal injury were found in 18 cases. The patients were treated with simple
      modified Magerl method (7 cases), cannutated screw fixation(6 cases), resection
      of C2,3 disc throuth the anterior approach and fusion with Zephir titanium plate
      (4 cases), percutaneous pedicle screw fixation of C2 (2 cases), release and
      reduction through anterior oropharynx (LRAO) combined with modified Magerl method
      (4 cases), LRAO and atlas lateral mass screw and plate fixation through posterior
      approach (3 cases), cervical occipital fusion through C2 pedicle (3 cases).
      RESULTS: All patients were followed up with an average time of 17.2 months
      ranging from 11 to 38 months. All patients obtained anatomical reduction and bone
      healing. Using Odom standard to evaluation for 18 cases with spinal injury before
      operation, the results were excellent in 9 cases,good in 7,fair in 2. No injury
      of vertebral artery, nerve root, spinal cord, infection of incisional wound,
      breaking or loosening of internal fixatir were found in the study. CONCLUSION:
      Identifying the causes of atlantoaxial instability, rational plan of operation
      can get satisfactory clinical results.

PMID- 19102266
TI  - [A controlled clinical trail of perioperative nutritional support of
      thoracolumbar spinal tuberculosis].
AB  - OBJECTIVE: To evaluate the influence of perioperative nutritional support on
      nutritional status of patients with thoracolumbar spinal tuberculosis. METHODS:
      Forty-eight patients with thoracolumbar spinal tuberculosis (male 25 and female
      23, aged from 35 to 60 years, with an average of 48.25 years) were randomized
      into two groups. Twenty-four patients nutritional support were increased
      intravenously for 14 days (7 days before and after operation) in experimental
      group. Twenty-four patients in control group were supplied with routine diet. The
      body weight, plasma concentrations of albumin and ESR were detected on the 7th
      day before operation and on the 7th day after operation. The total wound drainage
      was recorded and compared. RESULTS: Body weight and plasma concentrations of
      albumin on the 7th day after operation and those on the 7th day before operation
      were not significantly different in experimental group (P > 0.05). In control
      group, body weight and plasma concentrations of albumin on the 7th day after
      operation was lower than those on the 7th day before operation (P < 0.05). The
      total wound drainage of experimental group was less than that of control group (P
      < 0.05). ESR on the 7th day after operation was lower than that on the 7th day
      before operation in two groups (P < 0.05); but the decrease of ESR in
      experimental group was more than that in control group (P < 0.05). CONCLUSION:
      Nutritional support is beneficial to alleviating innutrition caused by tubercle
      bacillus and operation. It can promote the effects of operation and anti
      tuberculotic drugs.

PMID- 19102267
TI  - [Effect of BMI and WHR on lumbar lordosis and sacrum slant angle in middle and
      elderly women].
AB  - OBJECTIVE: To investigate the effect of body mass index (BMI) and waist hip ratio
      (WHR) on lumbar lordosis and sacrum slant angle in the patients with low back
      pain, and to discuss the theory of low back pain induced by obesity. METHODS: The
      Roland Disability Questionnaire (RDQ) was answered by 98 middle and elderly women
      with low back pain, whose body height, body weight, waist circumference, and hip
      circumference were measured and used to calculate their MBI and WHR. According to
      BMI, all the cases were divided into normal, overweight and obesity groups. These
      cases were also divided into noncentral and central obesity groups according to
      WHR. The lateral X-ray films of the lumbar spine were studied by measuring LCI,
      Cobb angle, and SSA. The data of all groups were analyzed statistically. RESULTS:
      LCI, Cobb angle, SSA and RDQ scores in the overweight and obesity groups are
      significantly higher than those in the normal group. LCI, Cobb angle, SSA, and
      RDQ scores in the central obesity group are significantly higher than those in
      the noncentral obesity group. CONCLUSION: BMI exceeding 24 kg/m2 or WHR exceeding
      0.85 may increase the measurements of Cobb angle, SSA and RDQ scores. Low back
      pain may occur because of overweight, obesity, or central obesity. The anatomy
      foundation of the increasing lumbar lordosis and sacrum slant angle may be the
      one of reasons of low back pain in obese person.

PMID- 19102268
TI  - [Fenestration with the spinous process resection in the treatment of central
      protrusion of lumbar intervertebral disc].
AB  - OBJECTIVE: To explore a operative approach and its effect to the central
      protrusion of lumbar intervertebral disc. METHODS: From February 1999 to December
      2005,34 patients with central protrusion of lumbar intervertebral disc were
      treated with an improved operative procedure. The study involved 25 males and 9
      females with an average of 46.4 years (range, 35 to 63 years). The involved level
      of herniation were at L4,5 in 20 cases and L5S1 in 14 cases. Pains happened on
      one leg fixedly and seriously with another lightly in 21 cases, on one leg
      initially and lightly with another seriously later in 8 cases, on bilateral legs
      alike in 5 cases. Preoperative CT film showed central type in 8 cases and
      laterocentral type in 26 cases. The corresponding spinous process was resected on
      the basis of unilateral fenestration. The supraspinous ligament was retained and
      pulled to the opposite side for revealing spinal canal, and then diskectomy was
      done. The above procedure was named "fenestration with the spinous process
      resection". RESULTS: All the 34 patients were followed up for 1 to 5 years. The
      outcome was evaluated according to the standard of HOU Shu-xun, 20 cases were
      excellent, 11 good and 3 fair. The total rate of excellent and good was 91.2%.
      CONCLUSION: The "fenestration with the spinous process resection" not only
      completed decompression of spinal canal and diskectomy, but also retained
      opposite lamina and supraspinous ligament and maintained the stability of
      posterior vertebral column, which are a new improved approach for the central
      protrusion of lumbar intervertebral disc.

PMID- 19102269
TI  - [Operative treatment on recurrence after chemonucleolysis of lumbar intervetebral
      disc herniation].

PMID- 19102270
TI  - [Surface-replacement total hip arthroplasty in the treatment of the femoral head
      osteonecrosis].
AB  - OBJECTIVE: To evaluate the outcome and indication of surface-replacement total
      hip arthroplasty in the treatment of the femoral head osteonecrosis. METHODS: The
      clinical data of 17 patients (21 hips) with femoral head osteonecrosis were
      reviewed. Among which, 10 cases were male and 7 cases were female, the average
      age was 36 years old (ranging from 25 to 51 years). There were 8 hips at Ficat
      stage III and 10 hips at Ficat stage IV. The 17 patients (21 hips) underwent
      surface-replacement total hip arthroplasty. Gibson posterolateral incision was
      used and non-cemented prosthesis was implanted. For prosthetic femoral head
      fixation, a guide pin was inserted into the capital center. After hollow boring
      hit drilling, a guide pole was inserted, and redundancy of femoral head was
      rasped off with cutterbar. The bone cement was painted on the femoral head and
      prosthesis, and the prosthesis was planted into the central axis hole of neck of
      femur until bone cement solidification. The therapeutic effects were evaluated by
      Harris hip score and statistical analysis was made. The X-ray was rechecked
      regularly. RESULTS: The mean duration of follow-up was 32 months (18 to 42
      months). The average Harris hip score was improved significantly from
      preoperative 35.30 +/- 5.23 to postoperative 90.47 +/- 3.14, and the excellent
      and good rate was 90.5%. There were high statistical differences between
      preoperative and postoperative Harris score (P < 0.01). The X-ray showed
      radiolucent line around acetabular prostheses in two patients but without
      prostheses loosening. CONCLUSION: Surface-replacement total hip arthroplasty is a
      satisfactory way for the treatment of femoral head osteonecrosis in the middle
      late phase, which can help reconstructing normal joint biomechanics and load
      transmission,improving joint stability and postponing THA without affecting later
      rebuilding, as well as some advantages such as decreasing surgical wound,
      convenient and low infection rate. Its indication is Ficat stage III and part
      Ficat stage IV femur head necrosis with less destroyed neck of femur,especially
      for young patients having a large amount of activity.

PMID- 19102271
TI  - [Destroy of stability construction at the lateral of ankle joint and its
      reconstruction].

PMID- 19102272
TI  - [Protection of apoptosis of osteoblast cultured in vitro by Morinda Root
      Polysaccharide].
AB  - OBJECTIVE: To explore the protection on apoptosis and the mechanism of promoting
      the cytoactive of osteoblast by Morinda Root Polysaccharide through the
      observations of the cultured osteoblast in vitro. METHODS: Prepared blood serum
      with Morinda Root Polysaccharide and Morinda Root aqueous extract and cultured
      Osteoblast in vitro with it. The second generation osteoblasts in vitro were
      separated from the cranium of 24-hours newborn SD rat, which were divided into
      control group (adding only rat serum during cultivation), induction apoptosis
      group (adding trans-retinoic acid in control group), Morinda Root aqueous extract
      group (adding serum prepared by Morinda Root aqueous extract in induction
      apoptosis group) and Morinda Root Polysaccharide group (adding serum prepared by
      Morinda Root Polysaccharide in induction apoptosis group). Adopting fluorescence
      microscope, apoptosis detected by flow cytometry and gene expression of Bcl-2 and
      Bax detected by RT-PCR, to evaluate the effect of Morinda Root Polysaccharide on
      the course of osteoblast apoptosis. RESULTS: The apoptotic rate of Morinda Root
      aqueous extract group and Morinda Root Polysaccharide group were significantly
      lower than that of induction apoptosis group (P < 0.01). The apoptosis ratio of
      Morinda Root Polysaccharide group was lower than that of Morinda Root aqueous
      extract group (P < 0.05). Expression level of Bcl-2 mRNA of apoptosis cell:
      control group > Morinda Root Polysaccharide group > Morinda Root aqueous extract
      group > induction apoptosis group (P < 0.01). Expression level of Bax mRNA:
      induction apoptosis group > Morinda Root aqueous extract group > control group >
      Morinda Root Polysaccharide group (P < 0.01). Bcl-2/Bax: control group > Morinda
      Root Polysaccharide group > Morinda Root aqueous extract group > induction
      apoptosis group (P < 0.01). CONCLUSION: Morinda Root can inhibit the apoptosis of
      osteoblast induced by trans-retinoic acid in some extent. The above role of
      Morinda Root Polysaccharide is significant better than that of Morinda Root
      aqueous extract. It is indicated that Morinda Root Polysaccharide is one of the
      essential component of inhibiting osteoblast apotosis.

PMID- 19102273
TI  - [Study of therapeutic effect and mechanism of Sihuang powder treating acute
      synovitis in experimental rabbit induced by papain injection].
AB  - OBJECTIVE: To prove the therapeutic effects of Sihuang powder (composed by four
      traditional Chinese herbs: root of baikal skullcap, bark of amur corktree, root
      of sorrel rhubarb, fruit of cape jasmine, which were mixed with wild
      Chrysanthemum flower solution)in treating acute synovitis in experimental rabbit
      knee osteoarthritic models induced by papain injection and to explore its
      mechanism. METHODS: Thirty-two New-Zealand white rabbits were divided into 6
      groups: blank group, model group, Sihuang powder with high dosage group (2 g/kg),
      Sihuang powder with low dosage group (1 g/kg), Yingtaiqing group and wild
      Chrysanthemum flower group. The latter four groups were treated respectively with
      low and high dose Sihuang powder synovium and cartilage were tested
      concentrations of nitrogen monoxide (NO) and IL-1 level and then were prepared
      for pathologic and histologic observation 10 days later. Cartilage pathologic
      changes were record and synovium pathologic changes were valued by means of
      Mankin's value system. RESULTS: The NO concentration of synovium in Sihuang
      powder with high dosage group was lower than that of model group, and there was
      significantly differences between the two groups (P < 0.01). The IL-1 level of
      synovium was failed after treated with Sihuang powder with high dosage (P <
      0.05). Sihuang powder with low dosage and Yingtaiqing also could restrain IL-1's
      release (P < 0.05). In Mankin's value system, Sihuang powder with high dosage
      almost eliminated inflammatory cells infiltrating in synovium, which was seldom
      found in other groups. The value of Sihuang powder with high dosage group was the
      lowest in treatment groups (P < 0.005). Sihuang powder with low dosage group and
      wild Chrysanthemum flower group also decreased the degree of inflammatory in
      synovium (P < 0.05). CONCLUSION: Sihuang powder can reduce the concentration of
      NO and IL-1 and improve inflammatory cell infiltrate in lining cells of synovium.
      Moreover, it can alleviate swelling and pain of joint, improve joint movement and
      postpone degeneration of the cartilage.

PMID- 19102274
TI  - [Treatment of soft tissue defects of anterior patellar region by the vascularized
      fascia flap].

PMID- 19102276
TI  - [Preliminary study on cryopreservation of tissue engineered bone at -8 degrees
      C].
AB  - OBJECTIVE: To study the effects of various methods of cryopreservation on the
      bioactivity of tissue engineered bone. METHODS: MSCs were cocultured with
      partialy deproteinised bone to produce tissue engineered bone. The experiment was
      divided into A, B, C and D group. Group A: Tissue engineered bone was stored in
      preservation solution with cryopreservation medium. Group B: Tissue engineered
      bone was stored in preservation solution without cryopreservation medium. Group
      C: Tissue engineered bone was stored without cryopreservation. Group D: MSCs were
      cultured without cryopreservation. The tissue engineered bone of group A and B
      had been cryopreserved at -80 degrees C for three months and thawed three months
      later. The electronic scanning microscope was used to evaluate the adhesion and
      distribution of MSCs, cell viability was measured by MTT, ALP activity was
      detected by p-nitrophosphate, cell cycle was analysed by flow cytometry. RESULTS:
      MSCs could adhere to the surface of the material and distribute in the hole of
      material. The cell viability of MSCs adhered to the material was C > A > B group
      (P < 0.01, P < 0.05). The ALP activity of MSCs adhered to material was C > A > B
      group (P < 0.01). The cell cycles of different groups did not change
      significantly; the abnormal cells were not observed. CONCLUSION: The choice of
      proper cryopreservative solution could optimize the bioactivity of tissue
      engineered bone.

PMID- 19102275
TI  - [One-stage toenail lengthening: a report of 9 cases].
AB  - OBJECTIVE: To summarize clinical application of one-stage toenail lengthening in
      free second toe transfer for reconstruction of the thumb (finger). METHODS: Nine
      patients (male 7, female 2) underwent thumb (finger) reconstruction with second
      toe transfer were treated by one-stage toenail lengthening technique. Eight were
      the thumb and 1 was the index finger. Patients aged from 18 to 46 years,with an
      average of 25 years. A rectangle skin was resected at 0.5 cm away from the
      eponychium, which was 0.2 cm high and as wide as the toenail. Then stripped U
      shape flap gently towards proximal end and sutured it. During the operation, the
      injury of the subcutaneous vascular network should be avoided. RESULTS:
      Superficial infection at donor area happened in 1 case and was healed by changing
      dressings. All the reconstruction thumbs (fingers) had survived completely. 2 to
      3 mm extending of toenail length was obtained and the appearance of thumb
      (finger) was improved. There was no growth deformation of toenail. After 7 to 24
      months follow up (the average time 13 months), the appearance of the nail was
      good. CONCLUSIONS: One-stage toenail lengthening in free second toe transfer for
      reconstruction of the thumb (finger), which can obtain a satisfactory appearance
      of the nail and have no influence on the motion of the reconstruction thumb
      (finger), is a simple and an effective operative procedure.

PMID- 19102277
TI  - [Treatment of fracture of the tubiform bone with domestic locking plate through
      minimal invasive incision and bridging reduction fixation].
AB  - OBJECTIVE: To study the therapeutic method and clinical effect of domestic
      locking plate for treating fracture of the tubiform bone through a minimal
      incision and bridging fixation. METHODS: Among 40 patients with fracture of the
      tubiform bone, 29 patients were male and 11 patients were female, aged from 29 to
      69 years, with the average of 38.27 years. Among 34 patients with closed
      fracture, 7 cases were type A, 10 cases type B, 17 cases type C according to
      AO/ASIF classification. Among 6 patients with open fracture, 2 cases were type I,
      4 cases were type II according to Gustilo classification. These patients were
      treated with a small incision after manipulative reduction. Locking plate and 3.5
      mm diameter Kirschner wire were used to maintain the reduction and through the C
      arm X-ray machine to check and adjust the position, screw were locked to bridging
      fixation at last. RESULTS: Forty cases were followed up in 6 months on average
      (ranging from 4 to 10 months). The average time of union of fracture was 4.6
      months (ranging from 3 to 8 months). According to Ovadia typing, the results were
      excellent in 16 cases, good in 20 cases, fair in 3 cases,poor in 1 case. The
      excellent and good rate was 90%. CONCLUSIONS: The domestic locking plate is
      suitable for patients with osteoporosis and comminuted fracture because of the
      advantages of reliable fixation and low price. It could achieve the same effect
      of minimal invasive as LISS (less invasive stabilizing system) plate through the
      improvement of operative method.

PMID- 19102278
TI  - [Surgical treatment for the intradural extramedullary tumor in the spinal canal].
AB  - OBJECTIVE: To study the clinical characteristics of the intradural extramedullary
      tumor in the spinal canal, as well as the application of internal fixation
      technique to restore the spinal stability in the surgical treatment of intradural
      extramedullary tumor in the spinal canal through posterior approach. METHODS:
      Among 24 patients receiving the tumor resection through posterior approach, 14
      patients were male and 10 patients were female, ranging in age from 12 to 68
      years, with an average of 40 years. Fourteen patients were treated with internal
      fixation and autogenous bone graft after tumor resection, and other 10 patients
      without internal fixation and autogenous bone graft. RESULTS: All the patients
      underwent one-stage resection of the tumor. During the follow-up period ranged
      from 6 months to 3 years (average 22 months), no recurrence of the tumor was
      found and the injury of spine cord did not aggravate, no vascular or nerve-root
      injury after the operation. The Frankle grades were improved by 1 to 3 degrees.
      Bone fusion formed at the corresponding bone grafted place. And there was no
      instrument broken or loosening. CONCLUSION: After the intradural extramedullary
      tumor is resected, internal fixation and autogenous bone graft can restore the
      stability of spine.

PMID- 19102279
TI  - [Curative effect of the fibrinogen gel for sacral canal arachnoid cyst].
AB  - OBJECTIVE: To evaluate curative effect of the fibrinogen gel for treating sacral
      canal arachnoid cyst. METHODS: Nineteen patients with sacral canal arachnoid
      cysts included 7 males and 12 females; The average age was 48.4 years ranging
      from 19 to 68 years. The course was from 2 weeks to 7 months. Of all the
      patients, 9 were in level of S1, 4 were in level of S1 to S2, 5 were in level of
      S2, 1 was in level of S1 to S3. Cystis wall greater partial excision adopted in
      11 cases, partial resection in 8, then all patients were treated by spray
      painting fibrinogen gel. RESULTS: Nineteen patients were followed-up for 13 to 30
      months (mean 21.3 months). The clinical symptom disappeared completely in 18
      patients, and only one patient urinated incapably, but after 2 weeks returned to
      normal. No one found recurrence by MRI after 12 months. CONCLUSION: This method
      of fibrinogen gel for treating sacral canal arachnoid cyst has advantages of easy
      performing, safety, achieve good results, less neck symptoms and early commencing
      of mobilization.

PMID- 19102280
TI  - [Treatment strategies for the diastasis of the symphysis pubis].
AB  - OBJECTIVE: To investigate treatment methods and therapeutic effects of the
      diastasis of the symphysis pubis. METHODS: Thirteen patients with diastasis of
      the symphysis pubis, including 7 male and 6 female, ranging in age from 20 to 54
      years,were treated according to classification based on the pelvic stability.
      Five patients of type I were treated with conservative methods, five patients of
      type II were treated with external fixation, and three patients with type III
      were treated with posterior internal fixation combined with anterior external
      fixation. RESULTS: All the patients were followed-up and the duration of the
      follow-up ranged from 4 to 62 months, with an average of 14 months. According to
      the reduction, pain,gait, limb length and movement of hip,the therapeutic effects
      were evaluated. There were 7 patients obtaining excellent results, 5 good, 1
      fair, the excellent and good rate was 92.3%. CONCLUSION: Treatment methods should
      be chosen in view of the differences of the patients with diastasis of the
      symphysis pubis. The external fixation has advantages of simple operation,
      decreased wound and stable fixation.

PMID- 19102281
TI  - [Effect comparison of two kinds of therapeutic methods of olecranon fracture].
AB  - OBJECTIVE: To compare the effects of olecranon plate and tension band in the
      treatment of olecranon fracture. METHODS: Sixty-three patients with olecranon
      fracture were treated with olecranon plate and tension band. Thirty-five patients
      (21 male and 14 female, aged from 15 to 62 years, with an average of 48.9 years)
      were involved in tension band group and 28 patients (20 male and 8 female, aged
      from 25 to 67 years, with an average of 50.6 years)were involved in plate group.
      According to the Delee, JC classification in 1984, there were type 1A in 5 cases,
      type 1B in 8 cases, type 2 in 17 cases, type 3 in 7 cases and type 4 in 1 case in
      tension band group; there were type 1A in 3 cases, type 1B in 5 cases, type 2 in
      6 cases, type 3 in 11 cases and type 4 in 3 cases in plate group. RESULTS: Sixty
      three cases were all followed up from 6 to 15 months. According to the criterion
      of PANG Gui-gen, the results were excellent in 20 cases, good in 7 cases, fair in
      1 case and no bad in plate group; the results were excellent in 23 cases, good in
      10 cases, fair in 21 case and no bad in tension band group. The therapeutic
      effect of two groups has no significantly statistic difference. CONCLUSION: Both
      olecranon plate and tension band are the effective treatments for olecranon
      fracture. The selection of two methods should depend on to the state of fracture.

PMID- 19102282
TI  - [Operative treatment of old scaphoid fracture].

PMID- 19102283
TI  - [Surgical treatment of Hoffa fractures].

PMID- 19102284
TI  - [Surgical treatment of posterior malleolar ankle fractures involving ankle
      mortise: a report of 58 cases].

PMID- 19102285
TI  - [Clinical study of treatment of discogenic low back pain by radiofrequency
      catheter ablation gasification system].

PMID- 19102286
TI  - [Treatment of surgical neck fracture of the humerus with percutaneous reduction
      of proximal part].

PMID- 19102287
TI  - [Reconstruction of right wrist joint with free grafting of the upper fibular
      myoperiosteum pedicle: a case report].

PMID- 19102288
TI  - [Comprehension of traditional medicine for vertigo and lumbago of spine-related
      disease].

PMID- 19102289
TI  - [Progress of anterior lumbar interbody fusion in clinical application].
AB  - Anterior lumbar interbody fusion (ALIF) has become a standard technique for
      interbody fusion since it was reported by O'Brien in 1983. Now it is used to
      treat many degenerative disease,such as lumbar discogenic pain, lumbar
      instability, lumbar spondylolisthesis and so on. In recent years, ALIF has
      developed greatly in clinical application. Minimal incision operation and
      laparoscopic anterior lumbar interbody fusion has been already performed, which
      made the operation less invasive. Many internal fixation instruments are used to
      improve the stability of ALIF. Interbody fusion devices were developed and the
      fusion rates enhanced greatly. At the same time, the complications of ALIF also
      has been realized. This paper overviews the current progress in the clinical
      application of ALIF.

PMID- 19102290
TI  - [Research process on dynamic stabilization system of low back pain].
AB  - Dynamic stabilization system plays an important role in the treatment of the
      degenerative lumbar spine. Fusion of short movement segments has little
      influences on the motion of lumbar spine. Meanwhile, preservation of movements of
      segment can prevent the degeneration of adjacent segment and maintain the
      possibility of disc replacement even under the condition that facet joints need
      to be excised. While maintaining the normal lumbar motion, dynamic stabilization
      system can not only decrease the load of intervertebral disc of corresponding
      movement segments and provide a good environment for the recovery of
      intervertebral disc and soft tissues, but also delay the degeneration of small
      facet and reconstruct the biomechanical function of spine.

PMID- 19102291
TI  - [Treatment of chronic osteomyelitis with antibiotic-loaded calcium phosphate
      cement].
AB  - The antibiotic delayed release system which has the characteristics of high local
      antibiotic concentration,few adverse effects, slow release and long duration, has
      became one of important methods of treating chronic osteomyelitis. Because of its
      double action as drug carrier and bone repair material which can induce bone
      growth and degrade synchronously, drug impregnated calcium phosphate cement
      (diCPC) is an ideal and safe antibiotic slow release carrier. After clearing
      focus thoroughly, defect implant with diCPC is an effective method, which has the
      virtues of convenient operation, good effects and short staying time etc. This
      paper aims to summarize the biological properties, experimental study and
      clinical application of diCPC.

PMID- 19102292
TI  - Successful strategies in atopic dermatitis management.
AB  - Successful strategies for managing atopic dermatitis require an accurate
      diagnosis, identification and elimination of exacerbating factors including
      irritants and allergens, adequate hydration of the skin, control of pruritus and
      infections, and appropriate use of topical anti-inflammatory and other
      medications. Proper patient education increases the chances of successful
      therapy.

PMID- 19102293
TI  - Eight ways to increase loyalty and retention in the workplace.

PMID- 19102294
TI  - Looking at the future.

PMID- 19102295
TI  - [Ecological benefit evaluation of urban forests in Shenyang City based on
      QuickBird image and CITYgreen model].
AB  - Based on the urban forest coverage data interpreted from QuickBird image (2006)
      and the CITYgreen model, the benefits of Shenyang urban forest types with
      different canopy closure in carbon fixation and pollutant removal were
      investigated by means of sampling strategy. The results showed that the total
      amount of carbon storage, annual carbon sequestration, annual air pollutant
      removal, and their corresponding values were 0.51 Tg, 6858.20 Mg x a-1), 556.04
      Mg x a(-1) 1.26 x 10(8) Yuan, 1.72 x 10(6) Yuan, and 0.22 x 10(8) Yuan,
      respectively. Among the urban forest types in Shenyang City, ecological and
      public welfare forest (E) contributed most to the carbon fixation and air
      pollutant removal. The carbon density decreased in the order of S (subordinated
      forest) > L (landscape and relaxation forest) > P (production and management
      forest) > E > R (road forest), annual carbon sequestration was in the order of P
      > L > E > S > R, and annual air pollutant removal was in the order of P > L > S >
      E > R. The carbon density of different urban forest types was closely related to
      their structural complexity. For the forests with high canopy closure, both the
      annual carbon sequestration and the annual pollutant removal were high; while for
      those with lower canopy closure, these two characteristics were dependent on the
      structural complexity of the forests.

PMID- 19102296
TI  - [Rainfall redistribution in subalpine Quercus aquifolioides forest in upper
      reaches of Minjiang River].
AB  - Based on the meteorological data from June to September 2007, the rainfall
      redistribution in subalpine Quercus aquifolioides forest in the upper reaches of
      Minjiang River was investigated by permanent plot method. The results showed that
      the total rainfall outside the forest was 486.7 mm, and the throughfall,
      stemflow, and canopy interception accounted for 82.6%, 0.9%, and 16.5% of the
      total rainfall, respectively. The throughfall and stemflow had significant linear
      relationships with rainfall (P < 0.01, n = 49), and the relationships of
      throughfall ratio and stemflow ratio with rainfall could be described with
      nonlinear curves. When the rainfall outside the forest was more than 3.2 mm,
      stemflow would happen, and there existed a significant exponential (R2 = 0.623)
      relationship between the stemflow volume and the tree basal area. The canopy
      interception rate decreased hyperbolically with the increase of rainfall, being
      significantly negatively correlated with the rainfall amount, duration, and
      intensity as well as the air relative humidity during rainfall (P < 0.01, n =
      49), but positively correlated with wind velocity (P < 0.01, n = 49).

PMID- 19102297
TI  - [Responses of subtropical conifer plantation to future climate change: a
      simulation study].
AB  - The responses of subtropical conifer plantation to climate change scenarios were
      investigated in Qianyanzhou by the process-based physiological-ecological model
      EALCO (ecological assimilation of land and climate observation). The results
      showed that CO2 concentration had the greatest effects on the carbon and water
      fluxes of the plantation, followed by temperature, and precipitation. CO2
      concentration was the main driving factor for the gross photosynthesis
      productivity of this plantation ecosystem, and temperature and CO2 concentration
      were the key environmental factors controlling the ecosystem respiration.
      Increasing temperature accelerated the respiration of aboveground part
      dramatically, while increasing CO2 concentration had greater effects on soil
      respiration. The evapotranspiration was enhanced by increasing temperature, but
      reduced by increasing CO2 concentration. Under the future climate changing
      scenario (the year 2100), the net primary productivity of this plantation
      ecosystem would be increased by 22%, suggesting that this ecosystem is still
      capable of sequestrating carbon.

PMID- 19102298
TI  - [Estimation of total carbon-containing gas emission from main tree species in
      forest fires in Daxing' an mountains].
AB  - By the method of emission factor (EF), this paper estimated the total carbon
      containing gas emission from five main tree species in Daxing' an Mountains in
      forest fires from 1980 to 2005. The results showed that different tree species
      had different EF. Pinus sylvesstris var. mongolica and Populus davidiana had the
      maximum and minimum EF of CO2, respectively. Larix gmelinii and Betula
      platyphylla had the maximun EF of CO and C(x)H(y), while B. platyphylla and L.
      gmelinii had the minimum EF of CO and C(x)H(y). Based on the carbon storage in
      different organs and the total biomass of the tree, it was estimated that the
      total emission of CO2, CO and C(x)H(y) from the five tree in the 25 years was
      16.58 Tg, 1.61 Tg and 0.54 Tg, and the contributions of L. gmelinii, P.
      sylvesstris var. mongolica, B. platyphylla, P. davidiana, and Quercus mongolica
      were 5.00 Tg, 0.63 Tg and 0.05 Tg, 0.225 Tg, 0.023 Tg and 0.003 Tg, 11.22 Tg,
      0.83 Tg and 0.41 Tg, 0.0022 Tg, 0.004 Tg and 0.00034 Tg, and 3.12 Tg, 0.13 Tg and
      0.062 Tg, respectively.

PMID- 19102299
TI  - [Estimation of forest volume in Huzhong forest area based on RS, GIS and ANN].
AB  - Based on remote sensing (RS) which has integrated and realistic characteristics,
      geographic information system (GIS) which has powerful spatial analysis ability,
      and artificial neutral network (ANN) which can optimize nonlinear complex
      systems, the forest volume in Huzhong forest area was estimated. The results
      showed that there was an obvious negative correlation between the forest volume
      and infrared band, indicating that infrared band had definite potential in
      estimating forest volume. The forest volume also negatively correlated with
      visible band and PC1. Among the topographic factors, altitude exerted more
      influence than aspect and slope on the estimation of forest volume. The
      correlation coefficient of predicted value and actual value reached to 0.973,
      when the optimal ANN parameter, suitable GIS information, and RS bands were
      adopted. After principal component transformation, the amount of observation data
      was effectively reduced, while the predicted precision only had a small decline
      (R2 = 0.934).

PMID- 19102300
TI  - [Prediction and mapping of potential vegetation distribution in Yanhe River
      catchment in hilly area of Loess Plateau].
AB  - The prediction and mapping of potential vegetation distribution is of instructive
      to the ecological restoration planning. By using generalized additive model (GAM)
      and in combining with GIS spatial analyst and environmental stratification
      sampling techniques, a distribution model for 24 dominant species in Yanhe River
      catchment was developed, and, based on the interspecific relationships in plant
      communities and the distribution probability, the spatial distribution of plant
      species was calculated, and the distribution of 37 plant communities and of the
      potential vegetation in Yanhe River catchment was predicted. The results showed
      that there were no significant differences between predictive values and actual
      data, and the predictive spatial distribution of vegetation could actually
      reflect the distribution of potential vegetation in Yanhe River catchment,
      suggesting that the established model had good ability for the vegetation
      distribution prediction, which was of significance to the goal-setting and
      planning of vegetation restoration.

PMID- 19102304
TI  - [Estimation of evapotranspiration from a typical marsh in Sanjiang Plain].
AB  - Eddy covariance technique was adopted in measuring the evapotranspiration (ET)
      from a typical marsh in Sanjiang Plain in the growth season (May to September) of
      2006. After analyzing the seasonal variation of the ET, the daily ET from the
      marsh was estimated by using Penman-Monteith (PM) and Priestley-Taylor (PT)
      models, and the estimated values were tested by the measured values. The results
      showed that the ET from the marsh had an obvious seasonal variation, with the
      lowest month-average daily ET in May and the highest one in July. The average
      daily ET in growth season was 1.94 mm x d(-1), and the total ET was 293 mm. The
      daily ET estimated by PM model was significantly lower than the measured one
      during the early and late growth seasons. A good match was observed between PT
      estimated values and measured values throughout the growth season. Considering
      its accuracy and simplicity, PT model was more suitable for the simulation of
      marsh ET.

PMID- 19102301
TI  - [Dry matter storage and water soluble sugar content in different age classes
      rhizomes of Phragmites communis population in dry land habitat of Songnen Plain
      of China].
AB  - Based on the investigation and measurement of Phragmites communis in a single
      dominant species community in dry land habitat of Songnen Plain, the seasonal
      variation of dry matter storage and water soluble sugar content in different age
      classes rhizomes at three growth stages were analyzed. The results showed that at
      all growth stages, younger age class rhizomes had lower dry matter storage and
      water soluble sugar content, and there was an obvious difference between younger
      and older age classes. The dry matter storage and water soluble sugar content in
      younger age class rhizomes increased rapidly with growth season, and the
      difference between younger and older age classes reduced gradually. In the whole
      growth season, all the rhizomes of six age classes kept up the activities in
      nutrient consumption, re-storage and even overcompensating storage, and the
      activities of younger age class rhizomes were much higher. The dry matter storage
      and water soluble sugar content in older age class rhizomes increased with year.
      There existed extremely significant differences (P < 0.01) in the dry matter
      storage within and among different age class rhizomes, and the difference was
      larger within age classes than among age classes. Significant differences (P <
      0.05) in water soluble sugar content were also observed among different age class
      rhizomes. The dry matter storage and water soluble sugar content in P. communis
      rhizomes increased in quadratic with increasing age class.

PMID- 19102302
TI  - [Physiological bases of herbages shade-tolerance in Eucalyptus grandis and
      herbage inter-cultivated system].
AB  - The study on the physiological bases of the shade-tolerance of Dactylis
      glomerata, Lolium perenne, and Hemarthria compressa inter-cultivated in
      Eucalyptus grandis forests with different canopy densities showed that with
      increasing canopy density, the light saturation point (LSP), light compensation
      point (LCP), chlorophyll a/b (Chla/Chlb), and the contents of proline (Pro),
      soluble sugar (SS) and soluble protein (SP) of the three herbages decreased
      gradually, but the apparent quantum yield (AQY), chlorophyll content (Chl),
      malondialdehyde (MDA) content, and superoxide dismutase (SOD) activity were in
      adverse. The daily average net photosynthesis rates (P(n)) of H. compressa
      decreased gradually, while that of D. glomerata and L. perenne increased first
      and decreased then. When the canopy density was below 0.54 for D. glomerata and
      below 0.27 for L. perenne, the P(n) of the two herbages was higher than CK. There
      existed significant correlations (P < 0.05) between 11 physiological indices of
      the three herbages and canopy density, and the shade-tolerance of the three
      herbages was in the order of D. glomerata > L. perenne > H. compressa, based on
      the ordination with average subjection function method.

PMID- 19102303
TI  - [Comprehensive assessment on control measures of Ambrosia artemisiifolia L].
AB  - Three control measures of Ambrosia artemisiifolia, including biological control,
      chemical control, and CK without any treatment, were evaluated by analytic
      hierarchy process (AHP). Corresponding contributions of the three control
      measures to comprehensive profit (CP) and comprehensive cost (CC) were calculated
      and ranked, which were regarded as the assessment criteria of the control
      measures. The results showed that among the three control measures, biological
      control had the highest CP and the lowest CC, CK was in adverse; and chemical
      control was in intervenient. Biological control had the highest ratio of profit
      to cost, and suggesting that this control measure is an optimal and recommendable
      measure in controlling A. artemisiifolia.

PMID- 19102305
TI  - [Distribution characteristics of soil phosphorus in maize belt farmlands of
      Northeast China].
AB  - The study on the vertical distribution and latitudinal differentiation of soil
      total and organic phosphorus (P) down to 100 cm depth in maize belt farmlands of
      Northeast China showed that in Hailun and Harbin of Heilongjiang Province,
      Gongzhuling of Jilin Province, and Dashiqiao of Liaoning Province, soil total P
      decreased with soil depth, being significant higher in 0-40 cm than in 40-100 cm
      (P < 0.01). In Dehui of Jilin Province and in Changtu and Shenyang of Liaoning
      Province, soil total P was relatively lower in 40-60 cm, but no significant
      difference was observed among different layers. Soil organic P was significantly
      higher in 0-20 cm than below 20 cm (P < 0.05). Soil total and organic P increased
      with increasing latitude (P < 0.05). The differences in climate conditions and
      soil types were considered as the main reasons induced the latitudinal
      differentiation of soil P. Soil total and organic P were significantly correlated
      with soil organic carbon (P < 0.01), indicating that soil organic matter was one
      of the most important factors affecting the soil P content and its distribution
      in maize belt farmlands of Northeast China.

PMID- 19102306
TI  - [Effects of long-term fertilization and fallowing on soil nitrogen mineralization
      and exogenous NO3(-) -N transformation].
AB  - Soil samples were collected from a 17-year fertilization experiment site in
      southern Loess Plateau to study the effects of different fertilizations and
      fallowing on the characteristics of soil nitrogen mineralization, and the
      transformation of exogenous NO3(-) -N in sterilized and non-sterilized soil
      samples. The results showed that a combined application of manure and chemical
      NPK and long-term fallowing increased the contents of soil organic matter, total
      N, and mineralized N, as well as the N mineralization rate significantly,
      compared with the control. Applying chemical NPK increased soil inorganic N
      content, but had less effects on the contents of soil organic matter, total N and
      mineralized N, as well as the N mineralization rate. Autoclaved sterilization
      resulted in a significant increase of soil NH4(+) -N content, while soil NO3(-) 
      N content remained relatively constant whether sterilization or not, suggesting
      that under the conditions of our incubation, abiotic and biological factors had
      no significant effects on the transformation of exogenous NO3 (-) -N.

PMID- 19102307
TI  - [Organic carbon mineralization in various size aggregates of paddy soil under
      aerobic and submerged conditions].
AB  - With incubation tests in laboratory, the mineralization of organic carbon in
      various size aggregates of paddy soil was investigated under aerobic and
      submerged conditions. The results showed that the organic carbon mineralization
      in various size aggregates decreased quickly at the beginning of the incubation,
      but remained stable during the late period of incubation. The mineralization rate
      varied significantly with the size of the aggregates. Through the incubation
      time, the organic carbon in 1-2 mm aggregates had the highest mineralization
      rate, while that in < 0.053 mm aggregates had the lowest one. Statistic analyses
      indicated that the mineralization rate of organic carbon in various size
      aggregates was significantly and linearly correlated with the contents of organic
      carbon and microbial biomass carbon in the aggregates. 0.25-1 mm aggregates had
      the highest contribution to the cumulative mineralization of soil organic carbon,
      accounting for 41.77% under aerobic condition and 34.11% under submerged
      condition, while < 0.053 mm and 1-2 mm aggregates had the lowest contribution
      under aerobic and submerged conditions, accounting for 7.8% and 6.6%,
      respectively.

PMID- 19102308
TI  - [Humus composition and stable carbon isotope natural abundance in paddy soil
      under long-term fertilization].
AB  - Soil samples were collected from an experimental paddy field with long-term (26
      years) fertilization in Taihu Lake region of Jiangsu Province to study the
      effects of different fertilization on the organic carbon distribution and stable
      carbon isotope natural abundance (delta 13C) in the soil profile, and on the
      humus composition. The results showed that long-term fertilization increased the
      organic carbon content in top soil significantly, and there was a significantly
      negative exponential correlation between soil organic carbon content and soil
      depth (P < 0.01). The organic carbon content in 10-30 cm soil layer under
      chemical fertilizations and in 20-40 cm soil layer under organic fertilizations
      was relatively stable. Soil delta 13C increased gradually with soil depth, its
      variation range being from -24% per thousand to -28 per thousand, and had a
      significantly negative linear correlation with soil organic carbon content (P <
      0.05). In 0-20 cm soil layer, the delta 13C in treatments organic manure (M), M +
      NP, M + NPK, M + straw (R) + N, and R + N decreased significantly; while in 30-50
      cm soil layer, the delta 13C in all organic fertilization treatments except R + N
      increased significantly. Tightly combined humus (humin) was the main humus
      composition in the soil, occupying 50% or more, and the rest were loosely and
      stably combined humus. Long-term fertilization increased the content of loosely
      combined humus and the ratio of humic acid (HA) to fulvic acid (FA).

PMID- 19102309
TI  - [Effects of relatively high temperature at grain-filling stage on rice grain's
      starch viscosity profile and magnesium and potassium contents].
AB  - With rice cultivars Yangdao 6 (Indica) and Wuyujing 3 (Japonica) as test
      materials, the effects of relatively high temperature (RHT, mean temperature 30
      degrees C) at grain-filling stage (GFS) on the starch viscosity profile and
      magnesium (Mg) and potassium (K) contents of rice grain were studied in a
      phytotron. Four temperature treatments were installed, i.e., RHT at whole GFS,
      RHT at early GFS and optimum temperature at later GFS, optimum temperature at
      early GFS and RHT at later GFS, and optimum temperature (CK, mean temperature 23
      degrees C) at whole GFS. The results showed that RHT at GFS significantly
      influenced the characteristic values of rice grain' s starch viscosity profile,
      e.g., the values of gelatinization temperature, final viscosity, consistency, and
      setback increased, while those of peak viscosity, hot viscosity, and breakdown
      decreased, with Yangdao 6 and Wuyujing 3 followed the similar pattern. The RHT
      increased the contents of Mg, K, and N, especially of K, resulting in a marked
      decrease of Mg/K and Mg/(N * AC * K) in the grain. The grain's amylase content
      (AC) of the two cultivars showed contrasting in response to temperature
      treatments. Wuyujing 3 performed decrease, while Yangdao 6 exhibited increase in
      AC values. The RHT at whole GFS affected the starch viscosity profile and the Mg
      and K contents most greatly, followed by the RHT at early GFS, and the RHT at
      later GFS. The period within 20 days after flowering was the key period during
      which temperature affected the grain's starch viscosity profile and Mg and K
      contents. The Mg/K and Mg/ (N * AC * K) in rice grain significant correlated with
      the characteristic values of starch viscosity profile, which could be used as the
      reference indices of rice eating quality.

PMID- 19102310
TI  - [Effects of irrigation amount and stage on water consumption characteristics and
      grain yield of wheat].
AB  - Field experiment was conducted in 2005 -2007 to study the effects of irrigation
      amount and stage on the water consumption characteristics, grain yield, and water
      use efficiency of wheat. The results showed that the variation coefficient of the
      proportion of soil water consumption amount to total water consumption amount was
      significantly higher than that of precipitation to total water consumption
      amount, suggesting the relatively wide regulation range of soil water use
      efficiency. The proportions of irrigation amount, precipitation, and soil water
      consumption amount to total water consumption amount were 31.0%, 38.9%, and 30.1%
      in treatment W3 (irrigated at jointing and flowering stages, with total
      irrigation amount of 120 mm), and 51.7%, 32.4%, and 15.9% in treatment W5
      (irrigated before winter and at jointing, flowering and grain-filling stages,
      with total irrigation amount of 240 mm), respectively, indicating that treatment
      W3 had a significantly higher proportion of soil water consumption amount to
      total water consumption amount than treatment W5. Though treatments W2 (irrigated
      before winter and at jointing stage) and W3 (irrigated at jointing and flowering
      stages) had the same irrigation amount (120 mm), the water consumption amount
      during the period from flowering to maturing was significantly higher in W3 than
      in W2, while the water consumption amount before jointing was significantly lower
      in W3 than in W2. The water consumption pattern in treatment W3 was in agreement
      with the water requirement pattern of wheat, which was the physiological basis of
      high water use efficiency.

PMID- 19102311
TI  - [Winter wheat yield gap between field blocks based on comparative performance
      analysis].
AB  - Based on a two-year household survey data, the yield gap of winter wheat in
      Quzhou County of Hebei Province, China in 2003-2004 was studied through
      comparative performance analysis (CPA). The results showed that there was a
      greater yield gap (from 4.2 to 7.9 t x hm(-2)) between field blocks, with a
      variation coefficient of 0.14. Through stepwise forward linear multiple
      regression, it was found that the yield model with 8 selected variables could
      explain 63% variability of winter wheat yield. Among the variables selected, soil
      salinity, soil fertility, and irrigation water quality were the most important
      limiting factors, accounting for 52% of the total yield gap. Crop variety was
      another important limiting factor, accounting for 14%; while planting date,
      fertilizer type, disease and pest, and water press accounted for 7%, 14%, 10%,
      and 3%, respectively. Therefore, besides soil and climate conditions, management
      practices occupied the majority of yield variability in Quzhou County, suggesting
      that the yield gap could be reduced significantly through optimum field
      management.

PMID- 19102312
TI  - [Spatiotemporal evolvement of soil microbiological characteristics in upland
      fields with different utilization duration in Cixi, Zhejiang Province].
AB  - The microbial number, microbial biomass, and enzymatic activities in five upland
      soils under agricultural utilization for 50-700 years were determined, with the
      correlations between soil microbiological characteristics and agricultural
      utilization duration analyzed. In the meantime, the functional diversity of
      microbes in soils having been utilized for 50, 100, and 700 years were
      investigated. The results showed that at the early stage (< 100 years) of
      agricultural utilization, the number of soil fungi (F) had a slight increase,
      while the bacterial number (B), B/F ratio, microbial biomass C (C(mic)),
      microbial biomass N (N(mic)), and the activities of catalase, invertase and
      urease all decreased markedly. After utilized for more than 100 years, the F
      decreased significantly, while the B, B/F ratio, C(mic), N(mic), and the
      activities of test enzymes all tended to increase. During the whole utilization
      period from 50 to 700 years, the C(mic)/N(mic) ratio had a significant increase
      with year. The Shannon, Simpson, and McIntosh indices of soil microbial community
      had the same responses to the agricultural utilization duration as the bacterial
      number, microbial biomass, and enzymatic activities. All of these indicated that
      in the upland fields in Cixi of Zhejiang Province, shifts of soil microbial
      community occurred with increasing agricultural utilization duration, and soil
      microbiological quality had an overall increase after 100 years agricultural
      utilization.

PMID- 19102313
TI  - [Effects of exogenous Ca2+ on leaf photosynthetic apparatus and active oxygen
      scavenging enzyme system of chrysanthemum under high temperature stress].
AB  - Taking cut flower chrysanthemum 'Jinba' as test material, the effects of
      exogenous Ca2+ on its photosynthetic system and antioxidant enzyme activities
      under high temperature stress were investigated, with the possible action
      mechanisms of Ca2+ discussed. The results showed that under high temperature
      stress, Ca2+ addition greatly inhibited the net photosynthesis rate (P(n)) and
      quantum yield of PS II electron transport (phi(PS II)). After 24 h treatment, the
      P(n) and psi(PS II) were increased by 31.11% and 21.88% , respectively, and the
      initial fluorescence (F(o)) decreased by 13.19%, compare with the control. Ca2+
      addition also greatly enhanced the activities of SOD, POD and CAT, and thus, the
      active oxygen was scavenged timely. After 24 h treatment, the MDA accumulation
      and REC were 29.20% and 35.81% lower than the control, respectively. In
      conclusion, Ca2+ addition could efficiently protect chrysanthemum leaves from the
      damage in photosynthetic apparatus under short-term high temperature stress.

PMID- 19102314
TI  - [Effects of NaCl stress on free polyamines content and reactive oxygen species
      level in pumpkin roots].
AB  - Taking Cucurbita moschata Duch hybrid 360-3 x 112-2 and C. ficifolia Bouche as
      test materials, the effects of NaCl stress on their plant growth and the O2*-
      production rate and H2O2 and free polyamines (PAs) contents in their roots were
      studied with hydroponic culture. The results showed that after 10 d NaCl stress,
      the plant growth of the two pumpkin varieties was strongly inhibited, compared
      with the control, and C. ficifolia was more injured than hybrid 360-3 x 112-2.
      Under NaCl stress, the root O2*- production rate and H2O2 content of the two
      pumpkin varieties were increased, but their absolute values were lower in hybrid
      360-3 x 112-2 than in C. ficifolia. The contents of PAs, putrescine (Put),
      spermidine (Spd) and spermine (Spm) and Put/PAs ratio in the roots of the two
      pumpkin varieties were always higher than the control and had a trend of
      increased first and decreased then; while the (Spd + Spm)/Put ratio was lower
      than the control and decreased first and increased then. Compared with C.
      ficifolia Bouche, hybrid 360-3 x 112-2 always had a lower Put/PAs ratio and a
      lower Put content in its roots, but the (Spd + Spm)/Put ratio and Spd and Spm
      contents were always higher. It was concluded that under NaCl stress, the
      increasing PAs content in the roots of test materials played an active role in
      decreasing or scavenging reactive oxygen species (ROS). The conversion of Put to
      Spd and Spm was advantageous to the increase of plant salt tolerance. The higher
      salt tolerance of hybrid 360-3 x 112-2 was closely related to the lower Put/PAs
      ratio and the higher (Spd + Spm)/Put ratio and PAs content in its roots, and
      thus, the stronger capacity to scavenge ROS.

PMID- 19102315
TI  - [Land use change and its driving factors in Mongolia from 1992 to 2005].
AB  - Based on the remote sensing images in 1992 and 2002 and the MODIS images in 2001
      and 2005, as well as relevant statistical information, the integrated
      characteristics and the spatial heterogeneity of land use change in Mongolia were
      analyzed, with the driving factors discussed. The results showed that from 1992
      to 2005, the area of farmland and forestland in Mongolia decreased significantly,
      that of construction land and unused land exhibited an increasing trend, water
      area showed a slight decrease, and grassland had less change in its area but
      declined in its quality. A significant regional difference was observed in the
      land use change, which mainly concentrated in the mountain areas of the western
      plateau and in the northern part of southern Gobi area. Both natural (climate
      change and natural disasters) and social (policies, regulations, and population
      increase) driving factors were responsible for the land use change in Mongolia.

PMID- 19102316
TI  - [Dynamics of land use landscape pattern in Hangzhou City during its rapid
      urbanization].
AB  - Based on the multi-temporal SPOT images of Hangzhou City in 1996, 2000, 2003, and
      2006, a method combining Principal Component Analysis (PCA) and hybrid classifier
      was adopted to accurately extract the land use change information. Meantime, the
      dynamics and characteristics of landscape pattern change were analyzed by using
      landscape indexes. The results showed that from 1996 to 2006, the rapid
      urbanization in Hangzhou induced a tremendous conversion of landscape pattern.
      Owing to the anthropogenic disturbance, the agricultural landscape was gradually
      replaced by man-made landscape, and the dynamics of the landscape pattern in
      Hangzhou exhibited complexity and diversity. Cropland landscape was impacted most
      seriously, being encroached at large scale; orchard landscape suffered from
      slight impact due to its small occupation in the landscape; forest landscape was
      insensitive to the impact due to its aggregated distribution; while water
      landscape was impacted greatly but exhibited slight fragmentation. Urban land
      landscape was the one undergone the biggest and quickest change.

PMID- 19102317
TI  - [A services value of different landscape types in Longitudinal Range-Gorge
      Region].
AB  - Based on the RS image of Longitudinal Range-Gorge Region (LRGR) in 2001, the
      study area was classified into seven first-class landscape types (forestland,
      grassland, farmland, wetland, water body, urban land, and glacier), and 26 second
      class landscape types in consideration of climate belt, vegetation, and
      topography. By using GIS technology, the services value of different landscape
      types of LRGR were studied in regards to the study results on services value of
      Chinese terrestrial ecosystems. The results indicated that the total services
      value of LRGR was 5 302.35 x 10(8) yuan x a(-1), accounting for 9.47% of the
      whole country. The service value of soil conservation was the highest, which
      occupied 18.05% of the total services value, while the service values of gas
      adjustability and biodiversity protection ranked the second and third. Due to its
      distribution extent and services intensity per unit area, the forest landscape,
      which covered 66.11% of the total area, contributed most (85.34%) to the total
      service value of LRGR, followed by grassland and farmland landscapes.

PMID- 19102318
TI  - [Effects of climate and land use change on the changes of vegetation coverage in
      farming-pastoral ecotone of Northern China].
AB  - Based on the remote sensing images and the meteorological data in 1986 and 2000,
      and by using the model of extracting vegetation coverage, the spatiotemporal
      changes of vegetation coverage in the farming-pastoral ecotone of Northern China
      in 1986-2000 were studied, with the effects of climate and land use change on the
      changes analyzed. The results showed that in this ecotone, the area with lower
      vegetation coverage was increasing, while that with higher vegetation coverage
      was in adverse. The regions with increasing vegetation coverage were mainly in
      the east of northeast section, the west of north section, and the west of
      northwest section of the ecotone, while the vegetation coverage in the other
      sections was obviously degraded. The vegetation coverage were positively
      correlated with precipitation and aridity index, but negatively correlated with
      temperature. The change direction and extent of the vegetation coverage varied
      with land use types.

PMID- 19102319
TI  - [Effects of rice-duck farming on paddy field water environment].
AB  - Field experiment was conducted to investigate the effects of rice-duck farming on
      the water environment in paddy field. The results showed that under rice-duck
      farming, the temperature and pH value of the surface water in paddy field
      decreased, and the electrical conductivity, oxidation-reduction potential,
      turbidity, and the contents of nitrogen (N), phosphorus (P) and potassium (K)
      increased. The total N, P, and K increased by 1.85-5.06 times, 2.01-8.70 times,
      and 42.79%-109.18%, respectively, as compared to those in conventional rice
      farming. All of these illustrated that rice-duck farming improved the paddy field
      water environment and nutrient supply, optimized the ecological environment of
      paddy field, and promoted the growth and development of rice.

PMID- 19102320
TI  - [Seasonal dynamics of phosphorus forms in water body and sediments of Nanhu Lake,
      Wuhan].
AB  - Water samples and sediment cores were taken at 5 sites of Nanhu Lake, Wuhan to
      investigate the seasonal dynamics of phosphorus in water body, sediments and
      their interstitial water, as well as the phosphorus forms in sediments. The
      results showed that the average concentrations of total phosphorus (TP) and
      orthophosphate (PO4(3-) -P) in water body were 0.240 and 0.033 mg x L(-1),
      respectively, with the highest concentrations of TP and PO4(3-)-P in November and
      the lowest concentration of TP and of PO4(3-) -P in February and August,
      respectively. The concentration of TP in sediments was averagely 1.005 mg x g(
      1), being increased from April to November and becoming stable from November to
      February, and decreased with sedimentation depth. The concentration of PO4(3-) -P
      in interstitial water was 0.209 mg x L(-1) on average, being the highest in
      November and the lowest in February, with the same vertical distribution pattern
      like TP in sediments. The dominant form of phosphorus in sediments was inorganic
      phosphorus (IP), occupying 61.4%-77.1% of total extracted phosphorus. The
      concentration of bio-available phosphorus (BA-P) in sediments was very high, but
      decreased significantly with sedimentation depth. According to the significant
      correlations between phosphorus forms in sediments and PO4(3-) -P in interstitial
      water, the BA-P and auto-calcium bound phosphorus (ACa-P) in sediments should be
      the main P sources released from sediments to water body.

PMID- 19102321
TI  - [Seasonal variation patterns of NH4(+) -N/NO3(-) -N ratio and delta 15 NH4(+)
      value in rainwater in Yangtze River Delta].
AB  - By using a customized manual rainwater sampler made of polyvinyl chloride
      plastic, the molar ratio of NH4(+) -N/NO3(-) -N and the natural 15N abundance of
      NH4(+) (delta 15 NH4(+) in rainwater was monitored all year round from June 2003
      to July 2005 at three observation sites (Changshu, Nanjing, and Hangzhou) in the
      Yangtze River Delta. The results indicated that at the three sites, the NH4(+) 
      N/NO3(-) -N ratio and the delta 15 NH4(+) value in rainwater had the similar
      seasonal variation trend, being more obvious in Changshu (rural monitoring type)
      site than in Nanjing (urban monitoring type) and Hangzhou (urban-rural monitoring
      type) sites. The NH4(+) -N/NO3(-) -N ratio peaked from early June to early
      August, declined gradually afterwards, and reached the bottom in winter; while
      the delta 15 NH4(+) value was negative from late June to mid-August, turned
      positive from late August to mid or late November, became negative again when
      winter dominated from December to March, but turned positive again in next May
      and negative again in next July. These seasonal variation patterns of NH4(+) 
      N/NO3(-) -N ratio and delta 15 NH4(+) value were found in relation to the
      application of chemical nitrogen fertilizers during different crop growth
      periods, and also, the alternation of seasons and the NH3 volatilization from
      other NH3 emission sources (including excrements of human and animals, nitrogen-
      polluted water bodies, and organic nitrogen sources, etc.), which could be taken
      as an indicator of defining the sources and form composition of NH4(+) in
      atmospheric wet deposition and the intensity of various terrestrial NH3 emission
      sources.

PMID- 19102322
TI  - [Ecological character of pelagic mysids in Yangtze Estuary of China].
AB  - Based on the four seasonal oceanographic cruises investigation data in the
      Yangtze Estuary (122 degrees 00'-123 degrees 30' E, 29 degrees 00'-32 degrees 00'
      N) in 2002-2003, the diversity and abundance dynamics of pelagic mysids as well
      as their relationships with fishing ground were studied. A total of 14 species
      were identified, among which, 10 species occurred in autumn, 8 species in spring
      and summer, and 2 species in winter. Clear seasonal alterations were observed,
      among which the highest alteration ratio (90.9%) occurred from autumn to winter.
      Shannon diversity index (H') in spring, summer and autumn was above 2, and that
      in winter was 1. Mean abundance was the highest in summer [234.70 ind x (100 m3)(
      1)], followed by in autumn [103.34 ind x (100 m3)(-1)], spring [80.36 ind x (100
      m3)(-1)], and winter [12.40 ind x (100 m3)(-1)]. The changes in mean abundance
      were in accordance with the fluctuation of seasonal temperature. Due to the
      adaptation to a wide range of temperature and salinity, Gastrosaccus pelagicus
      was dominant in spring, autumn and winter. Acanthomysis brevirostris was dominant
      in summer and autumn, and A. longirostrisas in winter. The dominant species in
      each season all made a significant contribution to total abundance. A.
      brevirostris was observed in large agglomerates in summer. As a kind of fish
      diet, mysids were of importance in the formation of fishing grounds in the
      Yangtze Estuary and Zhoushan Islands.

PMID- 19102323
TI  - [Comparison of mesozooplankton communities in North Channel and North Branch of
      Yangtze River Estuary].
AB  - According to the four cruises investigations in the Yangtze River Estuary from
      May, August and November 2004 and February 2005, and by using species diversity
      indices, K-dominance curves, and similarity analysis (ANOSIM), the features of
      mesozooplantkon communities and their dominant species in the North Channel (NC)
      and North Branch (NB) were analyzed, with the effects of ecological factors,
      especially water salinity and temperature, on the dominant species and
      communities in these two waters discussed. The results indicated that the NC was
      composed of tidal water and oligo-haline water, while the NB was featured by meso
      haline or poly-haline water. Consequently, the zooplankton communities in these
      two waters were significantly different. In spring, the abundance and diversity
      of the communities were larger in NB than in NC. In NC, Sinocalanus sinicus was
      the only dominant species; while in NB, there were several dominate species,
      among which, Labidocera euchaeta was most important. In summer, the diversity of
      the communities in NC and NB was quite similar, but the species richness and
      total abundance of zooplankton were less in NC than in NB. The zooplankton in NC
      was made up of olio-haline communities, and that in NB was composed of brackish
      species, e.g., Schmackeria poplesia and Tortanus vermiculus. In autumn, similar
      to those in spring, the abundance and diversity of the communities were larger in
      NB than in NC. As usual, in NC, S. sinicus was the most important species; while
      in NB, the zooplankton was composed of neritic community (Paracalanus parvus, P.
      aculeatus, L. euchaeta, and Calanus sinicus, etc. ). In winter, the species
      richness and diversity were the lowest, and there were no obvious difference
      between the zooplankton communities in NC and NB. It was concluded that water
      salinity, water temperature, and their combination were the key factors
      determining the characters of the mesozooplanktonic communities. Water
      temperature mainly affected the seasonal alteration of the dominant species,
      while water salinity, which was influenced by the interaction between runoff and
      ocean mass, determined the local mesozooplantkon communities in NC and NB.

PMID- 19102324
TI  - [Remote correlations between situation indicators of rice leaf roller during its
      immigration period in Jiangsu Province and sea surface temperature of west
      Pacific as well as their long-term prediction models].
AB  - The correlations between the situation indicators (peak time of ingoing, last
      length of peak period, and moth quantity in peak period) of rice leaf roller in
      Yixing, Yandu and Jingjiang of Jiangsu Province and the grid monthly sea surface
      temperature (SST) of west Pacific were analyzed by statistical method, and the
      correlation maps were produced by using GRADS software. The regions in which the
      SST was significantly correlated with the situation indicators were identified,
      and the SST at these regions, which was processed by optimization correlation
      technique, was used as the predictor to set up the long-term models for
      predicting the situation indicators of rice leaf roller during its immigration
      period in the three regions. The results showed that the immigration time of rice
      leaf roller in each of the regions was highly correlated with the SST in that
      region, and the duration of immigration peak was well correlated with the SST of
      west Pacific. The correlations between moth amount and SST were significant and
      stable, and showed some seasonality. Model calibrations indicated that the
      agreements between outputs from all models and observations were statistically
      significant (alpha = 0.01), and model validations demonstrated the applicability
      of the models developed in this study in predicting the situation indicators of
      rice leaf roller. These models were capable of predicting the possible occurrence
      situation of rice leaf roller one to two months in advance, being of significance
      in the prevention and control of rice leaf roller, suitable management of rice
      production, reduction of pesticide pollution, and protection of environment.

PMID- 19102325
TI  - [Coordination effect between vapor water loss through plant stomata and liquid
      water supply in soil-plant-atmosphere continuum (SPAC): a review].
AB  - Some important phenomena and behaviors concerned with the coordination effect
      between vapor water loss through plant stomata and liquid water supply in SPAC
      were discussed in this paper. A large amount of research results showed that
      plants show isohydric behavior when the plant hydraulic and chemical signals
      cooperate to promote the stomatal regulation of leaf water potential. The
      feedback response of stomata to the change of environmental humidity could be
      used to explain the midday depression of stomatal conductance and photosynthesis
      under drought condition, and also, to interpret the correlation between stomatal
      conductance and hydraulic conductance. The feed-forward response of stomata to
      the change of environmental humidity could be used to explain the hysteresis
      response of stomatal conductance to leaf-atmosphere vapor pressure deficit. The
      strategy for getting the most of xylem transport requires the rapid stomatal
      responses to avoid excess cavitation and the corresponding mechanisms for
      reversal of cavitation in short time.

PMID- 19102327
TI  - [Methods for river habitat survey and evaluation].
AB  - The study of river habitat is the basis for river ecological restoration and
      basin environmental management. In this paper, the classification, survey methods
      (including survey scale, sampling density, sampling season, and data recording),
      and data processing of river habitat were introduced, and the characteristics and
      application scope of the main methods (or models) widely applied in the world for
      river habitat evaluation were reviewed from the aspect of the relationships
      between living species and habitat suitability. Based on the approach of the
      experiences and methods of habitat research in developed countries, it was
      suggested that the river regulation in China should be carried out from the
      viewpoint of river ecosystem restoration.

PMID- 19102326
TI  - [Research and application advances on vegetative filter strip].
AB  - Water resources have been increasingly polluted, while vegetative filter strip
      (VFS) is accepted as one of the best management practices to reduce water body
      pollution, especially non-point source pollution. A vegetative filter strip is a
      vegetated strip of land, which separates the runoff and pollutant contributing
      areas from surface water bodies and allows the runoff and associated pollutants
      to be attenuated before reaching surface waters via infiltration, adsorption,
      uptake, decay, filtering, and deposition. In this paper, the research and
      application advances on VFS were reviewed, including the history, structure,
      mechanisms of pollution control, design, management, and cost effectiveness of
      VFS. The studies on VFS in China started recently, and very few results of
      experiments and applications had been achieved. In order to efficiently promote
      and use this ecological technique in China, more studies on VFS are needed to
      obtain relative experimental data and results.

PMID- 19102328
TI  - [Effects of microwave irradiation and electrostatic field on the survival, growth
      and reproduction of Moina mongolica Daday].
AB  - The study showed that 2 450 MHz microwave irradiation for 35 seconds or more had
      significant death effects on Moina mongolica Daday. Short-term (less than 25
      seconds) microwave irradiation could obviously increase the larvae number per
      clutch and the total fecundity over life span of the animal, with the highest
      fecundity under 10 seconds irradiation. Microwave irradiation could significantly
      prolong the life span (15.8-18 d) of M. mongolica. The short-term microwave
      irradiation had less effect on the development of larvae animal, but inhibited
      the adult growth to some degree. Impulse electromagnetic field could
      significantly increase the fecundity of M. mongolica, with the highest effect of
      29 kV x cm(-1); while high-voltage electrostatic field had less effect on the
      reproduction of M. mongolica. Both high-voltage and impulse electrostatic fields
      had no remarkable effects on the development of larvae animal. High-voltage
      electrostatic field had less effect on the growth of adult animal; while impulse
      electromagnetic field had definite inhibition effect on it, and the inhibition
      effect was increased with increasing voltage.

PMID- 19102329
TI  - [Suffocation point and diurnal metabolism pattern of Hemifusus tuba (Gmelin)].
AB  - The individuals of Hemifusus tuba (Gmelin) were divided into 3 groups, i. e.,
      small [S, (6.48 +/- 0.46) cm], medium[ M, (7.59 +/- 0.41) cm], and large [L,
      (9.08 +/- 0.37) cm], according to their shell height, and their suffocation
      points and diurnal metabolism patterns were investigated at water temperature (22
      +/- 0.5) degrees C. The results indicated that the oxygen consumption rate of H.
      tuba was relatively stable and maintained at 1.81 mg x g(-1) x h(-1) when
      dissolved oxygen (DO) content was higher than 4.37 mg x L(-1), but decreased with
      decreasing DO when DO content was lower than 4.37 mg L(-1) x 0.43 mg L(-1) of DO
      was the suffocation point of H. tuba, with the oxygen consumption rate being 0.
      The standard metabolism (SM) and routine metabolism (RM) of H. tuba decreased
      significantly with increasing body mass, and changed with the same pattern in the
      3 groups, i. e., being higher at night than in daytime. There was a significant
      difference in the SM (F = 36.263, P < 0.01) and RM (F = 6.788, P < 0.01) among
      the 3 groups. The peak values of the specific dynamic metabolism of groups S, M,
      and L were 2.11, 1.62, and 1.42 mg x g(-1) h(-1), being 1.09, 0.75, and 0.71
      times higher than their SM, respectively, and maintained about 15 h. The ammonia
      excretion rates of groups S, M, and L reached the peak after 24, 24, and 27 hours
      of feeding, with the peak values being 3.94, 2.64, and 1.71 micromol x g(-1) x h(
      1), and 0.87, 0.73 and 0.31 times higher than those in starvation state,
      respectively,.

PMID- 19102330
TI  - Cholecystectomy or not after percutaneous cholecystostomy for acute calculous
      cholecystitis in high-risk patients.
AB  - BACKGROUND/AIMS: This study aims to evaluate the outcomes of percutaneous
      cholecystostomy for acute calculous cholecystitis in patients with high surgical
      risk and determine whether subsequent cholecystectomy is beneficial and
      necessary. Percutaneous cholecystostomy has been shown to be a safe treatment
      option for patients suffering from acute cholecystitis but at high risk for
      emergency surgery. Controversies still exist on the approach of the
      cholecystostomy and the subsequent management of these patients. METHODOLOGY:
      From January 1996 to March 2004, percutaneous cholecystostomy was performed on 65
      patients that suffered from acute calculous cholecystostomy but were considered
      high risk for emergency surgery (American Society of Anesthesiologists grade III
      or IV). Their clinical outcomes were described and risk factors for in-hospital
      mortality and recurrence of cholecystitis were identified by univariate and
      multivariate analysis. RESULTS: Percutaneous cholecystostomy was successfully
      performed in all patients (100%). The clinical response rate was 91%. The in
      hospital mortality was 12.3%. Shock on admission was found to be a single
      independent risk factor for in-hospital death (p=0.006; odd ratio = 16.5; 95% CI
      = 2.2-123.1). Twenty-four patients underwent subsequent cholecystectomy whereas
      33 did not. The 1-year and 3-year recurrence of acute cholecystitis were 35% and
      46% respectively in patients who did not have subsequent cholecystectomy. Stone
      size > or = 1cm was independently associated with higher recurrence of acute
      cholecystitis (p=0.01; hazard ratio = 6.3, 95% CI 1.6-25.5). However, there was
      no difference in 1-year and 3-year overall survival between patients with or
      without cholecystectomy (82% Vs 81% and 59% Vs 63%, p=0.79). CONCLUSIONS:
      Percutaneous cholecystostomy is a safe and promising treatment for acute
      calculous cholecystitis in patients who are at high risk for emergency surgery.
      Cholecystectomy after the resolution of cholecystitis and optimization of
      associated medical illnesses is always advisable in order to prevent recurrent
      cholecystitis. However, the limited survival of these patients because of their
      old age and medical co-morbidities should be taken into consideration.

PMID- 19102331
TI  - Expression of vascular endothelial growth factor C is a prognostic indicator in
      esophageal cancer.
AB  - BACKGROUND/AIMS: Vascular endothelial growth factor plays an important role in
      angiogenesis and vascular endothelial growth factor-C is concerned with
      lymphangiogenesis. METHODOLOGY: The present study employed immunostaining to
      investigate the relationship between expression of these factors and
      clinicopathologic findings in 100 patients with esophageal cancer. RESULTS: Fifty
      six of the 100 tumors (56%) showed expressed vascular endothelial growth factor
      and 43 tumors (43%) expressed of vascular endothelial growth factor-C. Expression
      of the latter was correlated with the depth of tumor invasion (p=0.0095),
      lymphatic invasion (p=0.0065), lymph node metastasis (p=0.0l34). The prognosis
      was significantly worse for patients with tumors positive for vascular
      endothelial growth factor-C than for those with negative tumors (p=0.036). In
      contrast, expression of vascular endothelial growth factor was not correlated
      with the prognosis. Microvessel density was significantly higher in tumors
      expressing vascular endothelial growth factor-C compared with negative tumors
      (p=0.0014). Stepwise multivariate analysis with Cox's proportional hazards model
      identified gender (p=0.0420), age (p=0.0192), vascular endothelial growth factor
      C expression (p=0.0286), and lymphatic invasion (p=0.0030) as prognostic
      determinants. CONCLUSIONS: Expression of vascular endothelial growth factor-C is
      related to lymphatic invasion and is a prognostic indicator for esophageal
      cancer.

PMID- 19102332
TI  - Clinical utility of peroral cholangioscopy for mucin-producing bile duct tumor.
AB  - BACKGROUND/AIMS: The purpose of this study was to examine the clinical utility of
      peroral cholangioscopy for mucin-producing bile duct tumor. METHODOLOGY: Peroral
      cholangioscopy was performed in seven cases of mucin-producing bile duct tumor to
      decide the course of treatment based on the results. All seven cases were
      evaluated by peroral cholangioscopy and examined by a transpapillary biopsy. Five
      out of the seven cases (71.4%) were adequately observed. Because abundant mucin
      could not be removed in 2 cases (28.6%), one of them underwent PTCS after PTBD,
      and the other had surgery for EBD insertion without PTBD at the patient's
      request. A stent was placed by surgery in five out of the seven cases and by a
      transpapillary method in two cases. RESULTS: Among the five cases that could be
      evaluated by peroral cholangioscopy, the excised specimens were compared with the
      findings obtained from peroral cholangioscopy in three cases that underwent
      surgery, while the results of transpapillary mapping biopsy were compared with
      the findings obtained from peroral cholangioscopy in two inoperable cases,
      showing that the evaluation by peroral cholangioscopy agreed with the results of
      tumor staging in all the five cases. CONCLUSIONS: This study suggested the
      possibility that the use of peroral cholangioscopy for mucin-producing bile duct
      tumor could be useful in deciding the course of treatment.

PMID- 19102333
TI  - Telomerase activity of blood samples and recurrence of colorectal cancer.
AB  - BACKGROUND/AIMS: Recurrence, which occurs in about 20-30% of colorectal cancer
      patients after curative surgical treatment, is an important factor in determining
      prognosis. Therefore, early detection and prediction of recurrence is an
      important issue in the treatment of the disease. Telomerase is a reverse
      transcriptase that synthesizes telomere DNA, thereby compensating for telomere
      loss that occurs with each replication cycle, and limits proliferation cells.
      Telomerase is expressed in the majority of primary human tumors and hTERT is
      considered one of the most important proteins affecting telomerase activity. We
      evaluated telomerase activity in mesenteric and peripheral blood samples in
      addition to hTERT expression in cancerous tissues by means of
      immunohistochemistry in 120 patients who underwent curative surgical treatment at
      our department. METHODOLOGY: We investigated the factors correlated with
      recurrence. RESULTS: In univariate analysis, we found recurrence was
      significantly correlated with positive telomerase activity in the mesenteric vein
      (p=0.0021), positive telomerase activity in the peripheral vein (p=0.0032),
      histological type except well differentiated adenocarcinoma (p=0.0013), lymphatic
      infiltration (p=0.044), lymph node metastasis at surgery (p<0.0001), positive CEA
      (p=0.0004) and negative TERT immunoreactivity (p=0.012). In multivariate
      analysis, we found lymph node involvement at surgery (p=0.0045, hazard ratio:
      6.21) and positive telomerase activity in peripheral vein (p=0.037, hazard ratio:
      3.13) were significantly associated with the existence of recurrence.
      CONCLUSIONS: Our results show that measuring telomerase activity in peripheral
      blood samples is effective in predicting future recurrence to a degree greater
      than macroscopically examined tumor depth or other clinicopathological
      parameters.

PMID- 19102334
TI  - Video monitoring and slide and video presentations as tools for surgical
      education.
AB  - BACKGROUND/AIMS: To provide medical students with good visualization and
      understanding of surgical procedures, we used video monitoring (Monitor) in the
      operating room and slide (Slide) and video (Video) presentation in the
      conferences. The purpose of this study was to evaluate the effect of these visual
      aids on surgical education. METHODOLOGY: One hundred and twenty-nine fifth- and
      sixth-year medical students completed a questionnaire regarding their
      visualization of, understanding of, and interest in all surgical procedures
      observed and procedures pertaining to their assigned patients. The score was
      collected on a Likert-type scores ranged from 1 for "poor" to 5 for "excellent".
      RESULTS: Visualization and understanding scores were significantly lower for
      direct observation than for Monitor (p<0.01 and p<0.001), Slide (p<0.001 and
      p<0.001) and Video (p<0.001 and p<0.001). Interest scores did not differ between
      observation methods. For all observation methods, understanding of and interest
      in the surgical procedures were significantly greater in relation to assigned
      patients than in relation to all patients observed. CONCLUSIONS: Video monitoring
      and slide and video presentations enhance students' understanding of and interest
      in surgical procedures. Contributing to the care of assigned patient also
      increases understanding of and interest in general surgery.

PMID- 19102335
TI  - Strategies to reduce perioperative morbidity in cytoreductive surgery.
AB  - BACKGROUND/AIMS: Peritoneal carcinoma has been regarded as a uniformly lethal
      clinical entity. Cytoreductive surgery and intraperitoneal hyperthermic
      chemoperfusion (HIPEC) is an aggressive treatment for patients with peritoneal
      malignancies. While promising, this therapeutic regimen has been associated with
      significant morbidity, long hospital stay and an increased risk for perioperative
      mortality. The purpose of this study was to evaluate the possibility to reduce
      morbidity by use of strategy aiming to reduce inflammatory response associated
      with cytoreductive surgery plus HIPEC. METHODOLOGY: 241 consecutive patients
      underwent cytoreductive surgery plus HIPEC during the period of 4 years (1/03
      12/06). All patients were managed through multivisceral resection followed by
      HIPEC using an open technique. Peritonectomy was performed with the goal of total
      eradication of all visible tumor formations. RESULTS: 276 procedures were
      performed in 241 patients with 27 re-resections and 4 re-re-resections.
      Male/female ratio was 134/142. Mean age was 49 years (range 26-82). Optimal
      cytoreduction defined as CC-0 and CC-1 resection could be reached in 230 cases
      (83.3%). Complication rate (Feldman scale grade 3/4) and 30-day mortality rate
      were as follows: 2003: 26.5%, 2% 2004: 20%, 0% 2005: 14%, 1% 2006: 10%, 0%.
      CONCLUSIONS: The results of this study demonstrate the possibility to reduce the
      perioperative risk of cytoreductive surgery plus IPHC. The described strategy
      aiming the reduction of inflammatory response was able to reach a morbidity level
      which stands in line with other major oncologic operations.

PMID- 19102336
TI  - Expression of multidrug resistance-related proteins p-glycoprotein, glutathione-s
      transferases, topoisomerase-II and lung resistance protein in primary gastric
      cardiac adenocarcinoma.
AB  - BACKGROUND/AIMS: Multidrug resistance (MDR) is closely correlated to an
      unfavorable prognosis in various human cancers. However, the clinical
      significance of the expression of MDR-related proteins p-glycoprotein (PGP),
      glutathione-s-transferases (GST-pi), topoisomerase-II (Topo-II) and lung
      resistance protein (LRP) in primary gastric cardiac adenocarcinoma (PGCA) remains
      unclear. In this study, the total of the four kinds of MDR-related proteins
      mentioned above were detected by using immunohistochemistry and their clinical
      significance in chemoresistance were also investigated. METHODOLOGY: This
      retrospective study included 69 resected specimens from patients with PGCA. The
      expression of PGP, GST-pi, Topo-II and LRP in formalin-fixed paraffin-embedded
      tissue sections was determined by a labelled streptavidin-biotin
      immunohistochemical technique, and the results were analyzed in correlation with
      clinicopathological data. None of these patients received chemotherapy prior to
      surgery. RESULTS: The positive rates of expression of PGP, GST-pi, Topo-II and
      LRP in malignant tissues (49.2%, 75.4%, 68.1% and 58%, respectively) were all
      higher than that of the normal tissues (0, 30%, 20% and 0, respectively, P<0.01).
      PGP expression in tumors that had metastasized was significantly more frequent
      than in tumors that had not metastasized (67.5% vs. 24.1%, P<0.01).The expression
      of PGP was closely related with clinicopathologic staging (staging 1/2 vs. 3/4,
      28.6% vs. 58.3%, P<0.05). No significant correlation was shown between PGP and
      increasing differentiated degree (40%, 42.4% and 61.5%, P>0.05). GST-pi
      expression status progressively increased with increasing differentiated degree
      (40%, 75.8% and 88.5%, P<0.05) and clinico pathologic stage (staging 1/2 vs. 3/4,
      57.1% vs. 83.3%, P<0.05). In addition, a significant positive correlation was
      also observed between GST-pi and lymphatic metastasis (with vs. without
      metastasis, 87.5% vs. 58.6%, P<0.05). The expression of Topo-II was associated
      with increasing differentiated degree (33.3%, 69.7% and 80.7%, P<0.01). No
      significant differences with Topo-II expression was found in relation to the
      clinicopathologic stage (staging 1/2 vs. 3/4, 57.1% vs. 72.9%, P>0.05) and
      lymphatic metastasis (with vs. without metastasis, 65.0% vs. 72.4%, P>0.05).
      Moreover, a significant difference with the expression of LRP was found in
      relation to the clinicopathologic stage (staging 1/2 vs. 3/4, 38% vs. 66.6%,
      P<0.05), and lymphatic metastasis (with vs. without metastasis, 70.0% vs. 41.4%,
      P<0.05). Comparing the well, moderately and poorly differentiated cohort, a non
      statistical increasing trend towards LRP expression status was noted (50.0%,
      54.5% and 65.3%, respectively, P>0.05). Besides, the co-expression of all four
      tested MDR-related proteins also existed. The positive rates of co-expression of
      PGP and GST-pi, PGP and Topo-II, PGP and LRP, GST-pi and Topo-II, LRP and GST-pi,
      LRP and Topo-II, PGP, GST-pi, Topo-II and LRP in malignant cells were 23.2%,
      15.9%, 11.6%, 13.0%, 26.1%, 7.24%, 5.8%, respectively. CONCLUSIONS: MDR-related
      proteins PGP, GST-pi, Topo-II and LRP are involved in multiple mechanisms of drug
      resistance in PGCA. Combined determination of PGP, GST-pi, Topo-II and LRP may be
      prospectively valuable for optimizing the chemotherapy regimes, developing high
      quality anti-cancer drugs, and further predicting the outcomes of those patients
      with PGCA.

PMID- 19102337
TI  - Laparoscopic cholecystectomy in an ambulatory setting--initial experience in
      Croatia.
AB  - BACKGROUND/AIMS: The purpose of this study was to discover if ambulatory
      laparoscopic cholecystectomy is feasible in our environment and to determine the
      factors which will predict its success. METHODOLOGY: From November 12th 2002, to
      February 25th 2005 one hundred and fifty patients were admitted to our surgical
      ward of the General Hospital in Bjelovar due to cholelithiasis or biliary colic.
      Patients were unselected. Six to eight hours after the surgery we rated the
      ability of the patients to be discharged from the hospital (although they weren't
      discharged). RESULTS: The research has shown that 61% of the patients were
      eligible for ambulatory procedure. Among ultrasonographic attributes the most
      significant independent predictive factor of potential complications,
      prolongation of the procedure and ineligibility of the patient for the ambulatory
      laparoscopic cholecystectomy in our study was the thickened wall of the
      gallbladder. Among non-ultrasound preoperative attributes, the most important are
      the anamnestic data of prior cholecystitis and ASA classification. Pain was the
      most common reason why the patients were classified as non-candidates (36.6%). In
      the second place (25.4%) was the negative subjective patient's judgement to be
      discharged when all objective parameters were good. CONCLUSIONS: LC is also
      feasible in our environment but the patient's own motivation is the key factor in
      our situation.

PMID- 19102338
TI  - Medical students' attitudes to laparoscopic surgery.
AB  - BACKGROUND/AIMS: The purpose of the present study was to evaluate the attitude of
      medical students to laparosocopic surgery. METHODOLOGY: Two hundred and seven
      medical students completed a questionnaire regarding their visualization of,
      understanding of, and interest in observation of laparoscopic surgery via
      laparoscopic monitor (laparoscopic observation) and of open surgery, either
      directly (open direct observation), or via video monitor observation (open
      monitor observation). They were also asked about their willingness to become an
      operator (operator). Responses to each item were given as Likert-type scores
      ranging from 1 to 5. RESULTS: The visualization score was significantly lower for
      open direct observation than for open monitor observation (P<0.001) and
      laparoscopic observation (P<0.001), with the significantly lower score for open
      monitor observation than for laparoscopic observation (P<0.001). The
      understanding score was significantly lower for open direct observation than for
      open monitor observation (P<0.01) and laparoscopic observation (P<0.01). Interest
      scores did not differ between the three observation methods. The operator score
      was significantly higher for open surgery than for laparoscopic surgery.
      CONCLUSIONS: Laparoscopic surgery provides good visualization of the operative
      field. However, students' interest in laparoscopic surgery is similar to those of
      open surgery.

PMID- 19102339
TI  - Early conversion from oral morphine to transdermal fentanyl in patients with
      cancer pain.
AB  - BACKGROUND/AIMS: The aim of this study is to prove that an early conversion from
      oral morphine to transdermal fentanyl is an effective and safe treatment modality
      for patients with cancer pain. METHODOLOGY: Early conversion to transdermal
      fentanyl was evaluated for patients with cancer pain (VAS > or = 4) by
      administering 20-30 mg of morphine. RESULTS: The early conversion to transdermal
      fentanyl improved cancer pain in comparison to oral morphine. The mean VAS score
      improved to 2.6 +/- 2.8 after treatment, whereas the mean VAS score was 5.67 +/-
      2.4 before treatment by transdermal fentanyl. Eighteen of 24 patients (75%) were
      responders due to an early conversion by the VAS score, and the mean VAS score
      after transdermal fentanyl was 1.2 +/- 0.9 in responders. Finally, 66.7% of all
      patients received from 2.5 mg to 5.0 mg of transdermal fentanyl. The VAS score
      before conversion from oral morphine to transdermal fentanyl showed a significant
      difference (responder vs. non-responder: 4.7 +/- 1.8 vs. 8.5 +/- 1.4, P<0.001).
      Rescue treatment for cancer pain was required for 16 series in 13 patients.
      Vomiting, nausea, constipation, and drowsiness were observed as adverse effects.
      However, the nausea symptoms significantly improved after treatment with
      transdermal fentanyl (P<0.05). CONCLUSIONS: Early conversion from oral morphine
      to transdermal fentanyl helped to effectively relieve cancer pain while improving
      the effects of morphine induced nausea.

PMID- 19102340
TI  - Laparoscopic resection of HCC implanted in the peritoneal cavity: a case detected
      by PET after hepatic resection.
AB  - Intra-peritoneal implantation of hepatocellular carcinoma (HCC) after hepatic
      resection can occur in rare cases. Laparoscopic surgery is being rapidly adopted
      as a minimally invasive surgical technique for the treatment of HCC. Positron
      emission tomography with 18F-fluorodeoxyglucose can detect tumor by way of
      estimating the glucose metabolism of the tumor cells. We experienced a case of
      intra-peritoneal implantation of HCC that was depicted only by positron emission
      tomography and then treated by laparoscopic surgery. A 36-year-old male patient
      had undergone hepatic resection for HCC. In the course of the postoperative
      follow-up, the alpha-fetoprotein level had gradually risen. The positron emission
      tomography depicted a small tumor in the peritoneal cavity anterior to the spleen
      even though abdominal sonography, CT and celiac angiography had failed to detect
      it. The tumor was resected using laparoscopy, and it was revealed as HCC. Until
      now, no evidence of recurrence has been found for 3 years since the laparoscopic
      surgery. Intra-peritoneal implantation of HCC can be treated successfully with
      laparoscopic surgery, a minimally invasive surgery, in those selected cases such
      as with solitary HCC implantation.

PMID- 19102341
TI  - Life-threatening bleeding from duodenal varices due to pancreatic arterio-venous
      malformation: role of emergency pancreatoduodenectomy.
AB  - Life-threatening gastrointestinal bleeding due to arterio-venous malformation
      around the pancreatic head is a rare clinical entity. Herein we report a 60-year
      old male patient with uncontrolled bleeding from varices of the duodenum due to
      pancreatic arterio-venous malformation, who was treated by emergency surgery.
      Upper GI endoscopy revealed bleeding from juxta-ampullary duodenal varices. While
      contrast-enhanced CT demonstrated a hypervascular mosaic lesion in the region of
      the pancreatic head, subsequent selective angiography confirmed the presence of
      the malformation. The patient underwent selective transcatheter arterial
      embolization, but despite successful embolization of the gastroduodenal artery,
      bleeding continued and the patient became hemodynamically unstable, at which
      point he was referred to our department. He underwent an emergency
      pancreatoduodenectomy with exteriorization of pancreatic juice. During surgery
      the superior mesenteric vein was very thin (3mm) and was misdiagnosed as a right
      colic vein, and subsequently divided in this situation. After accomplishing
      pancreatoduodenectomy, the superior mesenteric vein was reconstructed. During
      reconstruction of the vein, small bowel congestion became apparent and a
      temporary porto-systemic bypass was created. Reconstruction was performed by the
      standard modified Child procedure except for exteriorization of the pancreatic
      juice. The patient made an uneventful postoperative recovery.
      Pancreatojejunostomy (2nd stage) was carried out three months after the emergency
      surgery. Emergency pancreatoduodenectomy is a definitive life-saving procedure
      when other forms of management such as transcatheter arterial embolization have
      been exhausted. In this rare situation, the superior mesenteric vein is extremely
      thin and therefore care should be taken not to damage it.

PMID- 19102342
TI  - A long-term survivor after pancreaticoduodenectomy for metastatic
      undifferentiated carcinoma of an unknown primary.
AB  - Undifferentiated carcinoma of unknown primary (CUP) is a relatively rare disease
      and carries a dismal prognosis. With this context, there is no report of a long
      term (> 5-year) disease-free survivor after a pancreaticoduodenectomy (PD). A 53
      year-old female had complaints of intermittent high fever and a large palpable
      epigastric tumor. A CT scan revealed that a very large well-circumscribed solid
      mass occupied the posterior portion of the head of the pancreas and extended to
      the hepatic hilum. The serum carcinoembryonic antigen (CEA), CA-125 and
      carbohydrate antigen 19-9 (CA19-9) levels were within the normal ranges. A PD
      with hepatic arterial reconstruction was performed. Histologically, the tumor
      showed solid or diffuse proliferation of pleomorphic cells, and the
      immunohistochemistry suggested a metastatic tumor originating from the
      epithelium, the primary site was not determined despite of full review of all
      metastatic lesions to pancreas handled surgically and non-surgically. Adjuvant
      oral chemotherapy of UFT and cimetidine continued for 3 years and the patient
      alive and healthy 6 years after surgery. Even for dismal prognostic
      undifferentiated CUP, radical surgery would be an effective component of
      multidisciplinary treatment, provided that the tumor is respectable without
      elevation of serum tumor markers and adjuvant chemotherapy is able to
      appropriately supplement.

PMID- 19102343
TI  - Defunctioning loop ileostomy with low anterior resection for distal rectal
      cancer: should we make an ileostomy as a routine procedure? A prospective
      randomized study.
AB  - BACKGROUND/AIMS: Anastomotic leakage is a major problem in colorectal surgery
      particularly in low rectal cancer. The defunctioning loop ileostomy was
      introduced as a technique to create a manageable stoma that would divert the
      fecal stream from a more distal anastomosis in order to reduce the consequences
      of any anastomotic leakage. Therefore, the use of a defunctioning stoma has been
      suggested, but limited data exist to clearly determine the necessity of routine
      diversion. This study was designed to evaluate early morbidity, mortality and
      hospital stay in patients undergoing lower rectal cancer surgery concerned with
      or without loop ileostomy. METHODOLOGY: This is a prospective randomized study
      that was performed between May 2001 and March 2008. There were 256 patients who
      underwent elective low anterior resection and stapler anastomosis. They were
      divided into two groups. Group A consisted of 120 patients who underwent straight
      anastomosis without ileostomy and group B consisted of 136 patients who underwent
      straight anastomosis with loop ileostomy. Data regarding patient demographics,
      underlying pathology, anastomotic problems, and ileostomy-related problems were
      gathered. The patients were all monitored closely after surgery for an
      anastomotic leak and all stoma-related complications were recorded. Inclusion
      criteria consisted of biopsy proven adenocarcinoma of the rectum located at < or
      = 5 cm above the anal verge, age > or = 22 years, and informed consent. Exclusion
      criteria included age more than 90 years, associated co morbid conditions Stage
      IV with disease spread to liver and peritoneum. RESULTS: Indications for surgery
      were lower rectal cancer (n=256). Mean age 55.5 years (range 22-90 years) and a
      male: female ratio of 1.1:1. All patients were undergoing elective surgery for
      lower rectal cancer. In our study 12 patients in group A developed anastomotic
      leak, two of them were re-explored for anastomotic leak and Hartman's colostomy
      was carried out. There were two deaths in Group A. In group B anastomotic leak
      was seen in three patients. In all three, anastomotic healing took place at a
      later period of time on the 18th, 20th, and 25th postoperative day respectively
      without any additional morbidity and mortality. Ileostomy-related problems were
      minor and limited to the stoma and complaints requiring stoma nurse evaluation
      (n=8), dehydration requiring outpatient care (n=3), bleeding at the stoma closure
      site (n=l). No stoma site hernias have been identified so far. CONCLUSIONS: The
      use of defunctioning loop ileostomy in all patients undergoing lower rectal
      surgery with stapler anastomosis is beneficial and safe. Defunctioning loop
      ileostomy use has resulted in no anastomotic leak rate and considerable low
      morbidity. So according to our study, we strongly recommend defunctioning loop
      ileostomy as a routine procedure in patients undergoing lower rectal cancer
      surgery.

PMID- 19102344
TI  - Projected dynamics of colonoscopic screening and surveillance for colorectal
      cancer.
AB  - BACKGROUND/AIMS: We used a simulation model of statistical analysis to estimate
      the cost and procedural burden of colorectal cancer (CRC) screening and
      surveillance using colonoscopy. METHODOLOGY: The estimated financial resources
      have been evaluated by multiplying half of the scheduled colonoscopies with the
      cost of one surveillance colonoscopy, dividing the result to the median time in
      which the procedures are performed, according to the Kaplan-Meier curve of
      scheduled procedures. RESULTS: Three hundred and thirty-eight patients (72.5%)
      were included in the registry for colonoscopic surveillance after a curative
      resection for colorectal cancer, 101 patients (21.7%) for follow-up after
      endoscopic polypectomies of adenomatous polyps, 21 patients (4.5%) for long
      lasting inflammatory bowel disease (IBD), and 2 patients (0.4%) for familial
      adenomatous polyposis. The projected dynamics and costs of colonoscopies
      scheduled for one year in our center indicate 11650 Euro/9.4 months spending for
      all procedures, 8450 Euro/8.8 months for surveillance after curative resection
      for CRC, 2525 Euro/24.9 months for surveillance after endoscopic polypectomies of
      adenomatous polyps and 525 Euro/6.8 months for screening for CRC in patients with
      long history of IBD, respectively. CONCLUSIONS: Screening and surveillance for
      CRC in a Romanian gastroenterology center represents an important activity in
      both workload and costs.

PMID- 19102345
TI  - No association between a genetic variant of the p22PHOX component of NADPH
      oxidase C242T and ulcerative colitis.
AB  - BACKGROUND/AIMS: Reactive oxygen species has been implicated in the development
      of ulcerative colitis (UC). NADPH oxidase, a major source of superoxide
      generation play a critical role in H. pylori related gastric inflammation. We
      aimed to clarify the effect of C242T polymorphism of p22PHOX, an essential
      component of NADPH oxidase on the risk of UC in a Japanese population.
      METHODOLOGY: 123 UC patients and 459 healthy control (HC) subjects participated
      in this study. The p22PHOX C242T polymorphism was determined by polymerase chain
      reaction-restriction fragment length polymorphism. RESULTS: In the HC group, the
      p22 PHOX genotype distribution was 379C/C (82.6%), 79C/T (17.2%), and 5T/T
      (1.2%). Meanwhile, the p22 PHOX geno type distribution in UC group was 96C/C
      (78.0%), 26C/T (21.1%), and 1T/T (0.9%). No significant difference of the p22
      PHOX genotype distribution was observed between HC and UC groups. (C/C vs. T/T;
      OR=0.80, 95% CI=0.09-6.84, C/C vs. C/T; OR=1.37, 95% CI=0.83-2.25, C/C vs. T
      carriers; OR=1.33, 95% CI=0.82-2.18, T/T vs. others; OR=0.74, 95% CI =0.09-6.43).
      No association was also found between p22PHOX gene polymorphism and different
      clinicopathological features of UC such as gender, age, age of onset, clinical
      type, extension of colitis and response to treatment. CONCLUSIONS: It appears
      that the C242T polymorphism of p22 PHOX is not associated with the incidence of
      gastric cancer in the Japanese population.

PMID- 19102346
TI  - An increase in the diagnosis rate of early colorectal cancer by sample targeting
      using stereomicroscopy: a two-year experience with 196 cases.
AB  - BACKGROUND/AIMS: To analyze the utility of stereomicroscopic evaluation for the
      diagnosis of early colorectal cancer using pit patterns and sample targeting and
      localized biopsy and the relationship between subclassification of the type IIIL
      pit pattern and histopathology. METHODOLOGY: A total of 196 colorectal neoplasms
      (including 110 colorectal neoplasms with type-IIIL pit pattern) were completely
      resected endoscopically and observed by stereomicroscopy from August 2005 to July
      2007. The histopathological results of the suspicious parts with pit patterns
      associated with early colorectal cancer under stereomicroscopy were compared with
      conventional pathological examinations slicing the entire specimen at random. We
      divided neoplasms with a type-IIIL pit pattern into three subclasses (IIIL-A IIIL
      B and IIIL-C), according to the morphologic and prominent stereomicroscopy
      findings. We examined the relation between these three subclasses and histology.
      RESULTS: The diagnosis rate of early colorectal cancer was 33.7% (66/196) by
      targeted and localized biopsy under stereomicroscopy, whereas it was only 6.1%
      (12/196) by conventional pathological examination (P<0.001). Subtype IIIL-C are
      significant predictors for early colorectal cancer. CONCLUSIONS: Sample targeting
      and localized biopsy under stereomicroscopy and subclassification of the type
      IIIL pit pattern is useful for improving the diagnosis rate of early colorectal
      cancer.

PMID- 19102347
TI  - A pathophysiological study using anorectal manometry on patients with or without
      soiling 5 years or more after low anterior resection for lower rectal cancer.
AB  - BACKGROUND/AIMS: Physiological assessments of the anorectum in patients with
      soiling 5 years or more after low anterior resection (LAR) are still
      inconclusive. The purpose of this study is to clarify the significance of
      anorectal functions in patients with soiling 5 years or more after LAR for
      lowerrectal cancer. METHODOLOGY: Thirty-eight patients after LAR for lower rectal
      cancer were manometrically studied and compared with 30 healthy volunteers as
      controls (group C; 19 men and 11 women, aged 44 to 76 with a mean age of 65.5
      years). Patients after LAR were divided into 2 groups [group A; 20 patients
      without soiling (13 men and 7 women, aged 47 to 75 years with a mean age of 62.1
      years), group B; 18 patients with soiling (12 men and 6 women, aged 51 to 77
      years with a mean age of 64.8 years)]. The mean follow-up time from LAR was
      67.2months (range 60-84 months). Anorectal manometry was performed on all
      patients in order to assess: Anal sphincter pressure at rest (ASPR; mmHg),
      Maximum anal sphincter pressure during voluntary contraction (MASPVC; mmHg),
      Minimum rectal sensory threshold volume (MRSTV; mL), Maximum rectal tolelated
      threshold volume (MRTTV; mL), Rectal compliance (RC; mL/mmHg), Rectoanal
      inhibitory reflex (RAIR), and Rectal pressure (RP; mmHg). RESULTS: The distance
      from the dentate line (DL) to the level of anastomosis in group B (2.2 cm) was
      significantly shorter than that in group A (4.1 cm) (p<0.05). ASPR in group B was
      significantly lower than that in groups A and C (p<0.05, p<0.01, respectively).
      MASPVC in group B was significantly lower than groups A and C (p<0.05, p<0.01,
      respectively). There were no significant differences of MRSTV among groups. MRTTV
      in group B was significantly lower than that in groups A and C (p<0.01, p<0.05,
      respectively). RC in group B was significantly lower than that in groups A and C
      (p<0.05, p<0.01, respectively). The frequency rate of positive RAIR in group B
      was significantly lower than that in groups A and C p<0.05, p<0.01,
      respectively). RP in group B was significantly higher than that in groups A and C
      (p<0.01, respectively). CONCLUSIONS: These findings support the hypothesis that
      soiling after LAR may be due to analsphincter and rectal dysfunctions. Increase
      of the RP also may cause soiling in patients after LAR. According to our studies,
      a length of remaining rectum 4 cm or more from the DL may be necessary to prevent
      soiling after LAR.

PMID- 19102348
TI  - Submucosal saline-epinephrine injection in colon polypectomy: appropriate
      indication.
AB  - BACKGROUND/AIMS: Opinions vary among endoscopists concerning the indications for
      submucosal saline-epinephrine injection for the prevention of postpolypectomy
      complications after colonic snare polypectomy. This study was performed to
      determine the appropriate indications for submucosal saline-epinephrine
      injection. METHODOLOGY: Clinical characteristics and complications (hemorrhage
      and perforation) in polypectomies were retrospectively evaluated. Postpolypectomy
      complications were analyzed in terms of demographic characteristics (age,
      gender), polyp characteristics (size, configuration, location, and
      histopathology), and the administration of submucosal saline-epinephrine
      injection. RESULTS: Total 1039 polypectomies were performed in 563 patients (age
      59.8 +/- 10.1 years), and submucosal saline-epinephrine injection was performed
      in 679 polypectomies. Twenty seven episodes (2.6%) of hemorrhage and 3 cases
      (0.2%) of perforation occurred. Malignant adenoma, a rectal polyp, and procedure
      without submucosal saline-epinephrine injection increased the risk of hemorrhage
      with odds ratios of 10.48, 4.71, and 3.44, respectively. Furthermore, submucosal
      saline-epinephrine injection significantly reduced the risk of hemorrhage in
      sessile polyps and those > 8 mm in size and with odds ratio of 16.41 regardless
      of location or histopathology. The occurrence of postpolypectomy perforation was
      not associated with any clinical characteristics and method. CONCLUSIONS:
      Submucosal saline-epinephrine injection should be performed for sessile polyps
      and those > 8 mm in size, and might be performed optionally in other cases to
      prevent postpolypectomy hemorrhage.

PMID- 19102349
TI  - Variation among endoscopy units in the achievement of the standards of
      colonoscopic performance indicators.
AB  - BACKGROUND/AIMS: To assess the achievement of quality standards of colonoscopy at
      six endoscopy units. METHODOLOGY: Three indicators were used to assess the
      quality of 1056 colonoscopies performed at six hospitals: cecal intubation;
      adequate colon cleansing; and removal and recovery of all detected polyps.
      Analyses were performed on the total number of colonoscopies and on colonoscopies
      in which polyps were actually detected. The accomplishment of each indicator and
      a global compound index of all three indicators, named the Problem Rate, were
      analyzed. Results from each endoscopy unit were compared to previously
      established standards. RESULTS: Adequate colon cleansing was the most frequent
      problem for quality in all centers; adequate colon preparation was 67% (range 50
      to 84%). The cecum was reached in 84% of all colonoscopies (range 76 to 90%). 75%
      of all patients (range 28. 79%) had all polyps excised and recovered. All centers
      had rates below standard for one or several indicators (p<0.01, all cases). Two
      of the participant hospitals had an overall problem rate above the estimated
      standard (p<0.01). CONCLUSIONS: There is a significant variation in the
      achievement of quality standards of colonoscopy between endoscopy units. Colon
      cleansing is the most frequent quality problem for colonoscopy.

PMID- 19102350
TI  - Clinical studies on anorectal myectomy for chronically constipated patients with
      outlet obstruction in childhood.
AB  - BACKGROUND/AIMS: To clarify the significance of anorectal myectomy (ARM) for
      chronically constipated patients with outlet obstruction (CCPOO) in childhood, we
      analyzed the clinical features of theses patients before and after ARM.
      METHODOLOGY: A consecutive series of one hundred and seven patients with CCPOO
      were included in this study. These were fifty-eight males and forty-nine females,
      aged between 0.2 and 15 years with a mean age of 8.9 years. We performed an
      analysis of the clinical findings and outcomes for CCPOO before and after ARM.
      RESULTS: More than half of the patients were under the age of 6.
      Neurohistochemical study showed hypoganglionosis (Hypo) in 71 patients [mild type
      (3/5 or more ganglion cells per ganglia): 51 cases, severe type (less than 2/5
      ganglion cells per ganglia): 20 cases], normal ganglia in 29, intestinal neuronal
      dysplasia (IND) in 2, and Hirschsprung's disease (HD; aganglionosis) in 5 (3
      cases were residual HD after Soave's or Duhamel's operation). Most of the
      patients were Hypo, followed by those who were normal and finally those who had
      other histological types (HD and IND) in decreasing order. Mild Hypo was the most
      common compared with normal ganglia and HD (P<0.001, P<0.00001, respectively).
      Abdominal pain was the most common symptom, followed by soiling and anal pain. In
      addition, abdominal pain was the most common complaint in Hypo patients, and
      severe Hypo patients had abdominal pain more frequently than those with mild Hypo
      (P<0.05). The most common outcome after ARM was good (72.0%), followed by poor
      (15.9%) and satisfactory (12.1%) in decreasing order. There were significant
      differences between good and satisfactory, and between good and poor (P<0.0001,
      respectively). In addition, good was the most common outcome in mild Hypo
      patients compared with severe Hypo (P<0.0001). Poor was the most common outcome
      in severe Hypo patients compared with mild Hypo (P<0.001). Spontaneous evacuation
      was recorded in 72.7% of good outcome patients, and 38.5% of those with
      satisfactory outcome after ARM. Regarding the use of laxatives, there were
      significant differences between good and satisfactory, between satisfactory and
      poor, and between good and poor outcome (P<0.05, P<0.01, P<0.0001, respectively).
      Colonic, psychological or central nervous disorders were found at high rates in
      patients with poor outcome. The most common related cause of constipation after
      ARM was a redundant colon. CONCLUSIONS: Hypo, IND, and HD may be largely related
      to defecation disorders observed in childhood CCPOO. CCPOO patients with colonic
      disorders, psychological or central nervous disorders may experience significant
      persistent constipation after ARM.

PMID- 19102351
TI  - Patient factors predicting the completion of sedation-free colonoscopy.
AB  - BACKGROUND/AIMS: Colonoscopy without sedation costs less than sedated
      colonoscopy. The aim of this study is to identify the patient factors predicting
      the completion of colonoscopy without sedation. METHODOLOGY: Between May and
      September 2005, a single colorectal surgeon performed 120 consecutive
      colonoscopies. Patient demographic, clinical and colonoscopy-related data were
      collected and analyzed. RESULTS: Out of 120 colonoscopies performed, 11 were
      excluded due to obstruction of the colon by a tumor or poor preparation.
      Therefore, the study group contained 109 patients. Ninety-three (85.3%)
      colonoscopies were completed. Completion rate (odds ratio for completion [95%
      confidence interval]) was significantly associated with the male gender (5.03
      [1.35-18.86]), high body mass index (4.42 [1.18-16.67]), no previous history of
      gynecological surgery (6.36 [1.84-22.14]), and previous colonic resection.
      Previous gynecological surgery was significantly associated with lower completion
      rates as shown using multivariate analysis. No complications relating to
      colonoscopy were observed. CONCLUSIONS: In the majority of patients, a colorectal
      surgeon with adequate endoscopy experience can perform sedation-free colonoscopy
      successfully and safely. Gender, previous gynecological surgery, previous colonic
      resection, and body mass index were predictive factors for successful colonoscopy
      without sedation.

PMID- 19102352
TI  - Open-label infliximab therapy in ulcerative colitis: a multicenter survey of
      results and predictors of response.
AB  - BACKGROUND/AIMS: Results of randomized controlled trials showing efficacy of
      infliximab in ulcerative colitis (UC) should be confirmed in clinical practice.
      We aimed to evaluate the efficacy and safety of infliximab in UC patients of the
      Madrid area, looking for clinical predictors of response. METHODOLOGY:
      Multicenter retrospective survey of all UC patients treated with infliximab in
      the region of Madrid (Spain). RESULTS: 47 UC patients were included (45% males,
      mean age 44 +/- 15 yrs), mean follow up of 4.7 months (range 0.5-21), and a total
      number of 211 infliximab infusions. Clinical response and steroid-free remission
      rates were, respectively, 97/42% in the 2nd week, 93/69% in the 6th week, and
      80/65% at the long-term follow up (mean 8.2 months, range 3.5-21). Colectomy rate
      was 10.6% (five patients). Age, gender, disease duration, indication (steroid
      resistance/dependence), disease severity, C-reactive protein, concomitant
      thiopurinic therapy or smoking habit did not influence on efficacy. Extent of the
      disease was the only predictive factor (p=0.02). Only 4 cases of mild adverse
      events were reported. CONCLUSIONS: Infliximab is effective and safe for UC. Real
      life clinical practice may have better outcome than showed in randomized
      controlled trials. Extent of the disease was the only predictive factor for
      clinical response in our experience.

PMID- 19102353
TI  - Clinical characteristics of Helicobacter pylori-negative duodenal ulcer disease.
AB  - BACKGROUND/AIMS: Previous data on H. pylori-negative duodenal ulcer (DU) are
      limited due to different exclusion criteria adopted. In this study we attempted
      to clarify the characteristics of H. pylori-negative DU disease from patients
      referred for endoscopy. METHODOLOGY: We recruited patients with DU disease and
      without H. pylori infection as confirmed by biopsy urease and 13C-urea breath
      tests. With each patient we carried out a structured personal interview including
      basic demographic and clinical data, personal habits, use of NSAIDs/aspirin,
      antibiotics, proton pump inhibitors (PPI) and anti-Hp therapy. If patients used
      antibiotics or PPI, a urea breath test was performed four or two weeks after
      discontinuation, respectively. RESULTS: The mean age of patients with H. pylori
      negative DU was 60.3 years (20-87). Among the 66 H. pylori-negative DU patients,
      34 (51.5%) had reported use of NSAID/aspirin, 24 (36.4%) had a history of
      previous eradication therapy. Among the 32 non-H. pylori and non-NSAID DU cases,
      five (15.6%) had psychophysical stress, four (12.6%) had co-morbid illnesses, and
      two (6.3%) were alcoholics. CONCLUSIONS: NSAID/aspirin use is the most common
      cause of H. pylori-negative DU disease. Psychophysical stress, co-morbid
      illnesses, and alcohol abuse appear to be associated with the development of non
      H. pylori and non-NSAID DU disease.

PMID- 19102354
TI  - Late recurrence of malignant melanoma in the duodenum.
AB  - Melanoma is a malignancy originating from melanocytes. The primary melanoma
      usually occurs on the skin, retina, anal canal or occasionally at other organs
      such as the esophagus, penis or vagina. Although melanoma represents about one
      third of all metastatic lesions in the gastrointestinal tract, metastasis of
      melanoma to the GI tract, detected radiologically or endoscopically, is
      relatively rare. In most cases of malignant melanoma, recurrence and death occur
      within 10 years after treatment of the primary lesion. We herein report a case
      showing a recurrence 17 years after extirpation of primary malignant melanoma in
      the foot. A 65-year-old man, with a history of extirpation of a malignant
      melanoma in the sole of his foot 17 years before, presented with anorexia and
      severe anemia, and multiple duodenal tumors were pointed out with upper
      gastrointestinal endoscopy. Histologic examination of the endoscopic biopsy
      specimen revealed proliferation of large polygonal cells with distinct nucleoli,
      and malignant melanoma was diagnosed immunohistochemically. Further examination,
      including computed tomography and positron emission tomography with
      fluorodeoxyglucose, revealed systemic metastasis.

PMID- 19102355
TI  - Reconstruction methods after total pharyngolaryngoesophagectomy: free jejunal
      graft and venous-reconstructed gastric tube or gastric tube alone.
AB  - BACKGROUND/AIMS: The aim of this study is to assess the postoperative outcome of
      the two reconstruction methods using both a free jejunal graft and a venous
      reconstructed gastric tube or a gastric tube alone after total
      pharyngolaryngoesophagectomy. METHODOLOGY: We reconstructed the pharyngoesophagus
      using both a free jejunal graft and a gastric tube in 5 cases (JG group),
      including 4 in whom the gastric vein was reconstructed, and using a gastric tube
      alone in 8 cases (G group). We compared the two groups in terms of postoperative
      complications, operation time, blood loss and length of postoperative hospital
      stay. RESULTS: In the JG group, jejunal graft necrosis occurred in a case,
      although 4 cases with gastric venous reconstruction had no postoperative
      problems. In the G group, although anastomotic trouble occurred in 3 cases, 7
      patients were discharged from hospital with oral feeding. In the JG group,
      postoperative stay was shorter, but the operation time was longer, than those in
      the G group. CONCLUSIONS: Reconstruction using a free jejunal graft and a venous
      reconstructed gastric tube is useful especially for patients with a long defect
      in the pharyngoesophagus. These 2 methods may be used according to the length of
      the pharyngoesophageal defect.

PMID- 19102356
TI  - Trans-abdominal-mediastinal approach with median phrenotomy for esophageal
      disruption.
AB  - BACKGROUND/AIMS: The prognosis for esophageal disruption is still poor. The aim
      of this study is to clarify the usefulness and safety of the transabdominal
      mediastinal approach for spontaneous esophageal disruption. METHODOLOGY: The
      surgical procedure is as follows: upper median laparotomy with resection of the
      xyphoid process, folding up of the lateral segment of the left liver, median
      phrenotomy from the root of the xyphoid process to the esophageal hiatus, trans
      mediastinal left thoracotomy by blunt dissection, blind lavage of the thoracic
      cavity, and simple interrupted suture and fundic patch of this suture line, if
      necessary. RESULTS: We managed 3 cases using this technique. Two cases had severe
      prior chronic diseases (poorly controlled diabetes and liver cirrhosis, and
      hemodialysis). In all cases, the lesions were completely exposed in the abdomen
      by and the ruptured sites were safely and completely sutured under a good field
      of view. The left thoracic cavity was adequately washed. All cases were saved
      without lethal complication. One case showed minor leakage, which was easily
      managed by continuous high pressure aspiration using double luminal drainage
      system (CHPA-DLD). CONCLUSIONS: We concluded that our technique is useful for
      esophageal disruption long after the onset, with severe prior chronic diseases,
      or with pleuritis.

PMID- 19102358
TI  - Prolonged antibiotic prophylaxis longer than 24 hours does not decrease surgical
      site infection after elective gastric and colorectal surgery.
AB  - BACKGROUND/AIMS: Prophylactic administration of antibiotics can decrease
      postoperative morbidity, shorten hospitalization, and reduce overall costs. In
      Western countries, it is stressed that antimicrobial prophylaxis was discontinued
      within 24 hrs after surgery in currently published guidelines. However, it is
      unclear how long we need to continue perioperative prophylaxis for
      gastrointestinal surgery. In this manuscript, we analyzed surgical site infection
      (SSI) in gastric and colorectal surgery according to the duration of antibiotics
      prophylaxis and discuss the duration of an antibiotic prophylaxis, and its
      relation to SSI. METHODOLOGY: We studied 228 patients who underwent digestive
      surgery including 94 with gastric cancer, 85 with colon cancer and 49 with rectal
      cancer. RESULTS: Overall SSI was seen in 28 cases (12.2%), 8 cases (8.5%) in
      gastrectomy, 10 cases (11.8%) in colectomy and 10 cases (20.4%) in rectal
      surgery. In SSI positive cases, operative time was longer (p=0.01), blood loss
      was more (p=0.01) and duration was longer (p=0.01) than in SSI negative cases.
      The duration of prophylactic antibiotics was significantly longer in 28 patients
      with SSI than in the 200 non-SSI patients (3.5 +/- 1.8 vs. 2.3 +/- 1.7 days;
      p<0.05). CONCLUSIONS: From our findings, SSI rate did not decrease with longer
      duration of antimicrobial prophylaxis. We concluded that we must recognize that
      the cause of postoperative wound infection is multimodal, and should not rely on
      antibiotics to prevent postoperative SSI but that surgeons should reduce the risk
      for postoperative SSI.

PMID- 19102357
TI  - A pilot trial of docetaxel and nedaplatin in cisplatin-pretreated relapsed or
      refractory esophageal squamous cell cancer.
AB  - BACKGROUND/AIMS: This study documents the clinical efficacy and toxicity of
      docetaxel and nedaplatin in cisplatin-pretreated relapsed or refractory
      esophageal squamous cell cancer. METHODOLOGY: From February 2002 to February
      2007, 20 patients with metastatic or locally recurrent or residual disease
      previously treated with cisplatin-based chemotherapy or chemoradiotherapy were
      included. The median age was 66.0 (range 52-74) years, and 17 patients had
      undergone a previous esophagectomy. A total of 36 cycles with docetaxel 60 mg/m2
      plus nedaplatin 80 mg/m2 were administered. RESULTS: The response rate was 25%
      including one complete response, and the rate of disease stabilization (% of
      complete response, partial response and stable disease) was 80%. The median
      progression-free survival was 14 weeks and the median overall survival was 26
      weeks. Severe neutropenia occurred in 12 patients (grade 3/4 = 4/8) and 5 out of
      20 patients showed severe febrile neutropenia (grade 3/4 = 4/1), whereas no
      severe non-hematological toxicity was observed. CONCLUSIONS: In conclusion, the
      combination chemotherapy of docetaxel and nedaplatin did not show drastic
      clinical efficacy. However, it was considered to be a feasible regimen as tumor
      dormancy therapy in CDDP-pretreated esophageal cancer, and to have a potent
      possibility to become a useful second-line chemotherapy for relapsed or
      refractory esophageal cancer. The control and prevention of severe neutropenia
      and febrile neutropenia is also very important in use of this regimen.

PMID- 19102359
TI  - Clinical characteristics of lower bowel perforation with chronic renal failure.
AB  - BACKGROUND/AIMS: This study was conducted to evaluate the clinical
      characteristics of lower bowel perforation (LBP) with chronic renal failure
      (CRF). METHODOLOGY: In 58 patients with LBP, clinical variables, such as findings
      of clinical examinations, operative findings, and results of laboratory blood
      tests were examined as possible prognostic factors for in-hospital death, and
      compared between CRF and non-CRF groups. RESULTS: Of the 58 patients, 21 died
      during hospitalization (mortality rate, 36.2%). The mortality rate of patients
      with CRF was 54.2%. In the patients with LBP, the following variables were
      significantly correlated with in-hospital death (p<0.05): hypotension, CRF, fecal
      peritonitis, and low white blood cell (WBC) count, and low albumin and base
      excess (BE) levels. The odds ratios of in-hospital death were highest for a WBC
      count of 9000/mm3 and a BE of -3mEqL. Between the CRF and non-CRF groups,
      significant differences in the rates of age < 70 years, fecal peritonitis, in
      hospital death, and low WBC count and BE were found (p<0.05). CONCLUSIONS: We
      identified prognostic factors of LBP and demonstrated the clinical
      characteristics of LBP with CRF. These results indicate that patients who have
      LBP with CRF tend to have immediate sepsis and a poor prognosis.

PMID- 19102360
TI  - Extensive atrophic gastritis linked to increased levels of intraluminal hydrogen
      gas.
AB  - BACKGROUND/AIMS: Gastric acid plays an important part in the prevention of
      bacterial colonization of the gastrointestinal tract. If these bacteria have an
      ability of hydrogen (H2) fermentation, intraluminal H2 gas might be detected. We
      attempted to measure the intraluminal H2 concentrations to determine the
      bacterial overgrowth in the gastrointestinal tract. METHODOLOGY: Studies were
      performed in 647 consecutive patients undergoing upper endoscopy. At the time of
      endoscopic examination, we intubated the stomach and the descending part of the
      duodenum without inflation by air, and 20 ml of intraluminal gas samples of both
      sites was collected through the biopsy channel. Intraluminal H2 concentrations
      were measured by gas chromatography. RESULTS: Over all, intragastric and
      intraduodenal H2 gas was detected in 566 (87.5%) and 524 (81.0%), respectively.
      The mean values of intragastric and intraduodenal H2 gas were 8.5 +/- 15.9 and
      13.2 +/- 58.0 ppm, respectively. The intraduodenal H2 level was increased with
      the progression of atrophic gastritis, whereas the intragastric H2 level was the
      highest in patients without atrophic gastritis. CONCLUSIONS: The intraduodenal
      hydrogen levels were increased with the progression of atrophic gastritis. It is
      likely that the influence of hypochlorhydria on bacterial overgrowth in the
      proximal small intestine is more pronounced, compared to that in the stomach.

PMID- 19102361
TI  - The effect of acid suppression on sleep and cardiac autonomic regulation in GERD.
AB  - BACKGROUND/AIMS: Autonomic dysfunction and sleep disturbances have been observed
      in patients with reflux disease. The study aim was to investigate whether acid
      suppression changed autonomic function and subjective sleep function in patients
      with erosive esophagitis. METHODOLOGY: Twenty-eight patients with erosive
      esophagitis underwent assessment of heart rate variability and a subjective sleep
      questionnaire. All patients were studied before and after esomeprazole or
      placebo. RESULTS: Esomeprazole resulted in a significant improvement in the
      reflux symptoms in week 8 (P<0.001). The global Pittsburgh Sleep Quality Index
      score decreased from 6.0 at baseline to 3.6 in week 8 in patients treated with
      esomeprazole (P<0.01). There was no significant change in any variable of heart
      rate variability in week 8 in either the esomeprazole or the placebo group.
      CONCLUSIONS: In 8 weeks, acid suppression therapy leads to an improvement in
      sleep disturbances but does not affect autonomic function. The study confirms the
      utility of acid suppression therapy for the resolution of not only reflux
      symptoms but also sleep dysfunction.

PMID- 19102362
TI  - EUS clarifies the natural history and ideal management of GISTs.
AB  - BACKGROUND/AIMS: Gastrointestinal stromal tumors (GISTs) are mesenchymal
      gastrointestinal tumors expressing C-kit (CD117). Endoscopic ultrasonography
      (EUS) evaluations of GISTs can help determine optimal therapy and follow-up care.
      The current study assesses the natural history of 100 GISTs evaluated by EUS, and
      the impact of EUS on their management. METHODOLOGY: Retrospective review of 2600
      EUS files performed over 11 years identified 100 patients with GISTs. Relevant
      data from all appropriate files and interviews with patients or family of
      deceased patients were tabulated regarding the GISTs. RESULTS: Every GIST had
      definitive cytology (n=43) or histology. Seventy of the 100 patients underwent
      more than one evaluation. Size of the GISTs at initial diagnosis averaged 20.5 mm
      and at follow-up examination 23.2 mm. Fourteen of 70 GISTs showed significant
      enlargement (> 1 mm/month). Enlargement during follow-up of GISTs was
      significantly more common with GISTs over 17 mm at initial diagnosis (p<0.018).
      Thirty-four were excised (7 endoscopically). Clinically asymptomatic GISTs tended
      to be smaller. Thirteen percent of GIST patients had second primary malignancy.
      CONCLUSIONS: EUS elucidates GIST natural history and can help guide management.
      GISTs larger than 17 mm should be monitored by EUS and considered for more
      aggressive treatment. Searching for synchronous tumors in patients with GISTs
      should be considered.

PMID- 19102363
TI  - Small bowel diverticulosis complicated by perforated jejunal diverticula:
      conservative and/or surgical management?
AB  - Small Bowel Diverticulosis (SBD) is rare and defined by the presence of multiple
      acquired mucosal herniations on the layer of the duodenal or jejunoileal loop.
      Usually asymptomatic, SBD is revealed by complications in 5 to 10% of cases. We
      report two cases of SBD complicated by perforated diverticula. The first case of
      perforation, revealed by an inflammatory anemia, required a surgical resection
      after failure of the first-intent medical treatment. The second case, revealed by
      fever and abdominal pain, was successfully managed by medical treatment. In case
      of SBD perforation, surgical management should be proposed as first-intent
      treatment in case of generalized peritonitis or after failure of first-intent
      medical treatment applied to localized peritonitis.

PMID- 19102364
TI  - Aggressive carcinoid tumors arising in the duodenum, ileum, and rectum with liver
      metastasis: a report of three cases.
AB  - Three aggressive carcinoid tumors with liver metastasis arising in the duodenum
      (Case 1, 72-year-old man), ileum (Case 2, 72-year-old man), and rectum (Case 3,
      67-year-old woman) were studied. Case 1 initially suffered from hemorrhage from
      an exophytic large tumor and developed a liver metastasis after operation. Cases
      2 and 3 first presented as multiple liver metastases. Case 3 had a small
      submucosal tumor and showed a relatively high cell proliferation activity.
      Neoplastic cells expressed gastrin in Case 1, serotonin in Case 2, and did not
      express several peptides in Case 3.

PMID- 19102365
TI  - Usefulness of multi-slice CT in a case with internal fistulas in Crohn's disease.
AB  - A case of Crohn's disease with an ileo-ileo fistula, ileal strictures and an ileo
      cyst fistula is reported. Laparoscopic operation that included partial
      ileoectomy, ileal stricturoplasty and dissection of the ileo-cyst fistula was
      performed. Multi-slice computed tomography (MSCT) that was performed before the
      operation showed an ileo-cyst fistula that was not detected by small bowel follow
      through or MRI. In this case, MSCT, including multi-planar reconstruction images,
      was significantly useful for evaluation of internal fistulas in Crohn's disease.

PMID- 19102366
TI  - Ribavirin priming in patients with chronic hepatitis C and normal ALT: a pilot
      study.
AB  - BACKGROUND/AIMS: Ribavirin has favorable immune-modulating effects in patients
      with hepatitis C. Therefore, a ribavirin monotherapy preceding the combination of
      peginterferon plus ribavirin may be beneficial. We conducted a pilot study with a
      sequential regimen using a reduced dosage of peginterferon-alfa 2b in patients
      with chronic hepatitis C and normal transaminases. METHODOLOGY: Twenty patients
      (17 genotype 1, 3 genotype 2/3) were treated with ribavirin for 4 wk followed by
      ribavirin plus peginterferon-alfa 2b 100 microg for 4 wk and ribavirin plus
      peginterferon-alfa 2b 50 microg for 44 wk. TH1-cytokines interferon-gamma and
      interleukin-2, and TH2-cytokines interleukin-4 and interleukin-10 were measured
      in the supernatant from PHA-stimulated lymphocytes. RESULTS: Sustained viral
      response defined as negative HCV-RNA after follow up was 50%, 41%, and 100% for
      all patients, genotype 1, and genotype 2/3, resp. The increase in interferon
      gamma following ribavirin monotherapy was significantly higher for patients with
      sustained viral response. CONCLUSIONS: The sustained viral response rate of this
      pilot study using ribavirin priming and reduced peginterferon dosage is in line
      with previous trials using standard treatment regimens for chronic hepatitis C.
      Our data stress the positive impact of the ribavirin-induced TH2-TH1 cytokine
      shift at least in patients with normal ALT. Larger clinical studies with
      ribavirin priming seem warranted.

PMID- 19102367
TI  - Liver transplantation for hepatocellular carcinoma and cirrhosis in candidates
      with undetectable or very low alpha-fetoprotein levels: is an expansion of the
      listing criteria justified?
AB  - BACKGROUND: Liver transplantation (LT) is the optimal therapy for hepatocellular
      carcinoma (HCC) in the setting of cirrhosis. The purpose of this study was to
      evaluate the results after LT for HCC patients with very low alpha fetoprotein
      (AFP) values both in our series and in literature reports. METHODOLOGY: Data
      obtained prospectively on 51 transplanted patients with HCC having AFP values <
      30 ng/mL preoperatively were analyzed. RESULTS: Four-year overall and recurrence
      free survival was 81% and 79%, respectively (median follow up of 35 months).
      Twenty nine patients (57%) were within the Milan criteria. Thirteen patients
      (25%) demonstrated advanced tumor stages. Ablative bridging treatments were
      attempted in 27 instances, and were associated with significantly worse overall
      and recurrence-free survivals (p=0.0209 and p=0.0111, respectively). Patients
      with AFP values < 30 ng/mL and no bridging treatments experienced 4-year overall
      and recurrence-free survivals of 96% and 95%, respectively. CONCLUSIONS: HCC
      patients with AFP values < 30 ng/mL who undergo LT with no bridging treatments
      experience excellent overall and recurrence-free survival rates, even with
      advanced tumor stages, independent of the Milan listing criteria.

PMID- 19102368
TI  - Quality assessment of randomized controlled trials involving liver surgery.
AB  - BACKGROUND/AIMS: In liver surgery as well as other surgical fields, many
      randomized controlled trials (RCTs) have been performed to date. However, there
      has not been any detailed quality assessment of these RCTs. Therefore, this
      article evaluated the quality of RCTs involving liver surgery. METHODOLOGY: A
      MEDLINE search was performed to identify prospective RCTs involving liver surgery
      published between January 1998 and December 2006. Eligible RCTs were evaluated by
      grading 5 items including sample size, calculation of sample size, randomization,
      intention to treat analysis, and loss to follow-up rate, allocating 0 to 2 points
      for each item. The total score as well as score for each item was compared
      between periods and countries. RESULTS: Seventy-three papers were eligible for
      review. Geographically, 40 RCTs were performed in Asia, 29 RCTs in Europe, and 4
      RCTs in North America. Dividing by country, the most papers were published by
      Japan. China, France, and Germany followed in numerical order. The mean total
      score was 5.9 points. The mean total score in the second half period (6.3) was
      significantly higher than that in the first half period (5.3) with significant
      increases in the scores for calculation of sample size and randomization method.
      The mean total score in Japan was the lowest among the top three countries, with
      a significantly lower score for sample size. CONCLUSIONS: RCTs involving liver
      surgery have been aggressively performed, especially in Asia and Europe. However,
      the quality of these RCTs is not so high. Improvement of internal validity with
      adequate study design is important to obtain reliable evidence.

PMID- 19102369
TI  - Albumin and prealbumin may predict retinol status in patients with liver
      cirrhosis.
AB  - BACKGROUND/AIMS: Impaired retinol status may be associated with development of
      cirrhosis to hepatocellular carcinoma (HCC). Besides cirrhotic severity, retinol
      may be influenced by compromised nutrition status. This study investigated the
      interrelations among retinol, malnutrition, and severity of cirrhosis and further
      aimed to examine whether malnutrition proxies commonly measured in hospital would
      be useful to predict retinol concentrations in different cirrhosis stages.
      METHODOLOGY: Fifty patients with liver cirrhosis, but without HCC were classified
      into the three Child-Pugh stages. Nutrition assessment was performed and fasting
      plasma retinol was analyzed using high-pressure liquid chromatography. RESULTS:
      Plasma retinol concentrations were significantly reduced as cirrhotic stage
      progressed accordingly (p for trend < 0.05). Stratified by each Child-Pugh class,
      subjects having albumin < 3.5 g/dL, prealbumin < 15 mg/dL and transferrin < 200
      mg/dL showed significantly lower retinol concentrations compared to their
      respective counterparts (p<0.05), except that all Child-Pugh C patients had
      prealbumin < 15 mg/dL or transferrin < 200 mg/dL. After adjusting for
      confounders, albumin < 3.5 g/dL (beta = -14.2, SE = 6.5, p=0.028) or prealbumin <
      15 mg/dL, (beta = -34.0, SE = 7.6, p<0.001) was negatively associated with
      retinol levels; transferrin < 200 mg/dL however. was not related. CONCLUSIONS:
      Retinol status was independently associated with malnutrition defined by albumin
      and prealbumin in cirrhosis patients. These malnutrition indicators are routinely
      measured by laboratory devices available in hospitals and may be used for
      prediction of retinol status in patients in different stages.

PMID- 19102370
TI  - Additional Hassab's operation for esophagogastric varices in cirrhotic patients
      with resectable hepatocellular carcinoma.
AB  - BACKGROUND/AIMS: The aim of this study was to clarify the role of the additional
      Hassab's operation to hepatectomy in cirrhotic patients with resectable
      hepatocellular carcinomas and esophagogastric varices. METHODOLOGY: Subjects were
      36 cirrhotic patients with hepatocellular carcinomas and concomitant
      esophagogastric varices: 20 underwent hepatectomy alone (non-Hassab group) and 16
      underwent hepatectomy with Hassab's operation (Hassab group). RESULTS: Patients
      in the Hassab group had more advanced esophageal varices and the accompanied
      gastric varices, preoperatively (p<0.01). Both preoperative platelet counts
      (p<0.01) and prothrombin time (p<0.05) were significantly lower in the Hassab
      group, and serum albumin level also tended to be worse than those in the non
      Hassab group. Portal pressure was significantly higher in the Hassab group
      (p<0.01). Despite these disadvantages, no significant differences were found in
      operative mortality, postoperative courses and long-term prognosis between the
      two groups. Comparing the cause of death, the incidence of the fatal variceal
      hemorrhage was significantly lower (0%) in the Hassab group than that (25%) in
      the non-Hassab group (p<0.05). CONCLUSIONS: This study suggested that additional
      Hassab's operation to hepatectomy might have reduced the risk of variceal
      hemorrhage after hepatectomy.

PMID- 19102371
TI  - An experience of hepatopancreatoduodenectomy in patients with hepatobiliary
      malignancies.
AB  - BACKGROUND/AIMS: In the advanced stage of hepatobiliary malignancies, concurrent
      hepatopancreatoduodenectomy (HPD) is necessary to accomplish curative resection,
      even though high rates of morbidity and mortality still remain. METHODOLOGY: We
      examined the surgical records and outcome in 11 patients undergoing HPD. RESULTS:
      In 11 patients, diseases included bile duct carcinomas in 7 patients, gallbladder
      carcinomas in 3, and ampullar carcinoma in one. Hemi-hepatectomy with resection
      of the caudate lobe was performed in 8 patients and resection of segment 4 and 5
      of the liver in two. Pancreatoduodenectomy (PD) was performed in 3 patients and
      pylorus-preserving PD in 8. Curative resection was accomplished in 8 patients.
      Two patients underwent adjuvant photodynamic therapy because of a cancer-positive
      margin. Morbidity rate was 36% but no hospital deaths were reported. The tumor
      recurrence rate was 73% and 8 patients died of cancer. Patient prognosis of
      gallbladder cancers (12 +/- 1 months) tended to be shorter than in patients with
      bile duct cancers (19 +/- 11 months) (p=0.15). Three patients with bile duct
      cancers survived without tumor relapse over 12 months. CONCLUSIONS: Complete
      surgical resection (R0) by HPD could be safely performed for diseases of the
      hepatobiliary malignancies, which achieved longer survival in some patients.

PMID- 19102372
TI  - Hand-assisted laparoscopic hepatectomy for tumors located in posterior segment.
AB  - BACKGROUND/AIMS: In spite of recent advances in laparoscopic surgery,
      laparoscopic approach is still not a standard option for the tumors located in
      the posterior segment of the right hepatic lobe mainly due to its technical
      difficulties and the risk for injuring major adjacent vessels. METHODOLOGY: In
      order to evaluate the feasibility of laparoscopic posterior segment hepatectomy
      (LPSH) compared to open posterior segment hepatectomy (OPSH), we retrospectively
      reviewed a total of 46 laparoscopic hepatectomies and 169 open hepatectomies.
      Among them, three patients underwent LPSH and seven patients underwent OPSH for
      tumors located in the posterior segment of the right hepatic lobe. RESULTS:
      Although duration of operation showed a trend toward being longer in LPSH, LPSH
      was not accompanied by significant increase of blood loss. Furthermore, LPSH had
      a trend to result in earlier recovery of the patients, including shorter hospital
      stay and earlier start of walking or meal. CONCLUSIONS: In conclusion, our data
      suggested that LPSH could be as safe and feasible as OPSH for tumors located in
      the posterior segment.

PMID- 19102373
TI  - Starting a new program of split liver transplantation after a low learning curve:
      a reality in centers with large experience in liver surgery and whole liver
      transplantation.
AB  - BACKGROUND/AIMS: Split liver transplantation (SLT) is nowadays, considered an
      adequate surgical solution to expand the grafts from the existing pool of
      cadaveric donors. METHODOLOGY: A total of 897 liver transplantations were
      performed between 1986 and 2002; 20 were SLTs (2.3%). A 30% were children.
      RESULTS: Mean follow up of 15.15 months +/- 13.85. Median age was 42.27 +/- 25.65
      yrs. Median recipient weight was 52.29 +/- 20.87 Kg. Mean donor weight was 76.1
      +/- 13.11. The majority was "in situ" SLT (65%). There was no primary graft
      dysfunction. Two patients developed biliary complications (none in situ SLT).
      Early HAT occurred in 2 patients and delayed HAT in one. Four patients were
      retransplanted but none were performed because of primary graft dysfunction. Five
      patients died in the hospital. Fifteen patients (75%) survived the postoperative
      period and 3 patients died during follow-up. Mean patient survival time was 42
      months (95% CI: 31-52). Actuarial patient survival was 93.3%, 84.4%, 84.4% at 6
      months, 1 year and 3 years. Mean graft survival was 36 months (95% CI: 25-48).
      Actuarial graft survival was 87%, 72%, 72% at 6, 12, 36 months. Univariate
      analysis of risk factors for graft loss showed that the type of splitting
      technique (p=0.019), and the UNOS (1 and 2a) status of the recipient (p=0.001)
      were significantly associated with graft loss. CONCLUSIONS: In the context of
      large volume full cadaveric liver transplantation, split liver can provide
      adequate results (even after a short learning curve) mainly in elective cases and
      with the in situ technique.

PMID- 19102374
TI  - Serum alpha-fetoprotein level per tumor volume reflects prognosis in patients
      with hepatocellular carcinoma after curative hepatectomy.
AB  - BACKGROUND/AIMS: The clinical usefulness of alpha-fetoprotein (AFP) in the
      management of hepatocellular carcinoma (HCC) remains controversial. This study
      aimed to assess the prognostic reliability of serum AFP levels per tumor volume
      (AFP/volume) after curative resection. METHODOLOGY: A total of 196 patients with
      HCC were analyzed with reference to serum AFP levels at diagnosis.
      Clinicopathological data included presence of cirrhosis, indocyanine green
      retention rate (ICGR15), tumor size and number of HCCs. Tumor volume for HCCs was
      calculated preoperatively by Computed tomography volumetry, and AFP/volume was
      calculated by dividing serum AFP level by tumor volume. RESULTS: No significant
      correlation between serum AFP levels and presence of cirrhosis or ICGR15 was
      observed. A significant correlation existed between serum AFP levels and both
      size (P=0.001, r=0.276) and number (P=0.023, r=0.186) of HCCs. The 5-year
      survival rates in patients with low (< 200 ng/mL) and high (> or = 200 ng/mL)
      serum AFP level were 85.0% and 36.0%, respectively. AFP/volume tended to be
      negatively associated with survival period (p=0.084, r = -0.346), and a
      significant negative correlation existed between AFP/volume and disease-free
      survival period (p=0.001, r = -0.347). Median values of AFP/ volume in patients
      who displayed recurrence by 1 year and 6 months were 11.51 and 20.05,
      respectively. CONCLUSIONS: AFP/volume represents a better prognostic indicator
      for patients with HCC than serum AFP value alone. In particular, patients with
      AFP/volume > 20.0 are likely to experience recurrence within 6 months after
      curative hepatectomy.

PMID- 19102375
TI  - Comparison of core and fine needle aspiration biopsies for diagnosis of liver
      masses.
AB  - BACKGROUND/AIMS: Core biopsy of liver mass comprises an alternative to fine
      needle aspiration biopsy. We decided to compare diagnoses established with the
      use of both methods and assess whether the use of both methods together is
      warranted. METHODOLOGY: Each of the 116 patients enrolled in study underwent a
      guided fine needle and core biopsy of liver tumor. The results were compared.
      Histopathologic diagnoses of carcinomas were supported by immunohistochemistry
      (anti-CK7, anti-CK19, anti-CK20 and Hepatocyte antibodies). RESULTS: In 83 out of
      116 cases (71.5%), major cytological and histopathological diagnoses (malignancy
      vs. benign lesion vs. diagnosis impossible) were univocal. In one case,
      establishing diagnoses was not possible due to 'non-diagnostic' material
      harvested during both biopsies. In 15 cases, diagnoses were established solely on
      the basis of one examination In 13 cases, histopathologic diagnosis was contrary
      (malignant vs. benign) to cytologic diagnosis. In 27 cases histopathologic
      examination enabled us to reach more precise diagnosis than cytological
      examination. Despite the simultaneous use of both methods, we were able to
      establish definite diagnoses only in 29.3% of malignant cases. CONCLUSIONS:
      Although core biopsy provided more information and more precise information than
      fine needle biopsy, most complete results were achieved with the use of both
      methods together.

PMID- 19102376
TI  - Dense packing of portal lymphocytes predicts favorable treatment outcome in
      hepatitis C.
AB  - BACKGROUND/AIMS: To identify pre-therapeutic predictors of sustained virological
      response (SVR) in Taiwanese patients with chronic hepatitis C. METHODOLOGY: One
      hundred and ninety-eight consecutive patients receiving interferon plus ribavirin
      combination therapy were included. Stepwise logistic regression model was
      performed to estimate the SVR on the presence of various pre-therapeutic clinical
      parameters. RESULTS: The difference of alanine aminotransferase and aspartate
      aminotransferase levels (beta = 0.0080, P=0.0151), the presence of genotype 1b
      (beta = -1.9225, P<0.0001), the presence of dense packing of inflammatory cells
      in portal tract (beta = 1.5239, P=0.0354), age (beta = -0.0441, P=0.0179) and pre
      therapeutic HCV-RNA concentration (beta = -0.0682, P=0.0411) were identified as
      independent predictors in the regression analysis. Patients with dense packing of
      inflammatory cells in portal tract (n=21) had significantly higher aspartate
      aminotransferase concentration, higher histology activity index, higher fibrosis
      score, and more histologically cirrhosis (P=0.032, 0.0001, 0.034, and 0.020,
      respectively). Paradoxically, they had a higher chance to achieve SVR (18/21
      (85.7%) versus 99/177 (55.9%); P=0.017). CONCLUSIONS: Dense packing of
      inflammatory cells in portal tract is an independent predictor of SVR to
      antiviral therapy in patients with chronic hepatitis C.

PMID- 19102377
TI  - Occult hepatitis B virus infection in chronic hemodialysis patients in Korea.
AB  - BACKGROUND/AIMS: Occult HBV infection that is serum HBsAg negative but HBV DNA
      positive is thought to be a contributing factor to ongoing HBV transmission
      within hemodialysis units. In the present study, the prevalence of occult HBV
      infection was investigated in patients on chronic hemodialysis in Korea, an
      endemic region for HBV. METHODOLOGY: Eighty-three patients undergoing maintenance
      hemodialysis at Samsung Medical Center, Seoul, South Korea were included. Serum
      samples were obtained from all patients. Testing for HBsAg, anti-HBs and anti-HBc
      was performed by an electrochemiluminescence immunoassay. HBV DNA was detected by
      the nested PCR method. RESULTS: Among the 83 patients, 4 (4.8%) were HBsAg
      positive and HBV DNA positive. The remaining 79 patients were confirmed HBsAg
      negative/HBV DNA-negative. Thus, the prevalence of occult HBV infection was 0%.
      All of the HBsAg-positive patients were anti-HBs-negative/anti-HBc-positive. Of
      79 HBsAg-negative patients, 58 (73.4%) were anti-HBs positive and 52 (65.8%) were
      anti-HBc positive. CONCLUSIONS: The present study showed that the prevalence of
      occult HBV infection in chronic hemodialysis patients at our center in Korea was
      not increased compared to the rates of low endemic regions. Furthermore, occult
      HBV infection was not a contributing factor in HBV transmission in the
      hemodialysis unit studied.

PMID- 19102378
TI  - Clinical significance of detailed preoperative evaluation on donors in right lobe
      living donor liver transplantation.
AB  - BACKGROUND/AIMS: To investigate the clinical importance of detailed preoperative
      evaluation on donors of right lobe graft in living donor liver transplantation.
      METHODOLOGY: Between January 2001 and August 2006, 106 potential donors were
      screened and evaluated. Evaluation focused on imaging study of hepatic vascular
      system, bile duct system, hepatic volumety and hepatic steatosis. RESULTS: A
      total of 81 women (77.88%) and 23 men (22.12%) were evaluated with 51 donors
      participating. 55 potential donors were rejected. One donor failed to complete
      donation hepatectomy due to 40% macrovesicular steatosis found during operation.
      Variation of portal vein and hepatic artery could be found with evaluation.
      However, variations of hepatic veins especially the tributaries of middle hepatic
      vein and right hepatic bile duct showed on CT scan were not concordant with those
      at the cut surface of the liver graft. All the 50 right lobe grafts did not
      include middle hepatic vein, weighing 400-850 g (media 550 g), accounting for
      31.74-71.68% (mean 45.35%) of standard liver volume (SLV) of the recipients.
      Donor morbidity, including all complications, was 8% with no mortality. All the
      donors recovered uneventfully. CONCLUSIONS: Detailed evaluation for hepatic lobar
      volume, vascular anatomy, virtual resection planes and morphologic features is of
      clinical importance in the selection of suitable donor in living right liver
      transplantation.

PMID- 19102379
TI  - Effects of GSTT1, GSTM1 and GSTP1 gene polymorphism on the course of hepatitis B
      virus infection.
AB  - BACKGROUND/AIMS: To investigate the effects of GSTT1, GSTM1 and GSTP1 gene
      polymorphism on the stage of hepatitis B infection. METHODOLOGY: This study
      included 116 healthy controls, 56 normal carriers of hepatitis B virus, 69
      chronic hepatitis B patients and 20 cirrhosis patients. The polymorphism of
      GSTT1, GSTM1 and GSTP1 were determined with real time PCR with LightCycler
      instrument using hybridization probes in combination with the LightCycler DNA
      Master Hybridization Probes Kit (Roche Diagnostics). Multivariate binary
      logistics regression analyses were used for statistical evaluation. RESULTS:
      GSTP1 IIe/val genotype was significantly more frequent in the patients with
      chronic hepatitis B infection and in the patients with cirrhosis (p=0.049 OR:
      1.909, 95% CI 0.993-3.668 and p<0.001 OR: 15.238, 95% CI 1.971-117.782
      respectively) than in the healthy controls. Similarly, GSTP1 val/val genotype was
      significantly more frequent in the patients with chronic hepatitis B infection
      and in the patients with cirrhosis (p=0.006 OR = 6.799, 95% CI 1.712-26.99 and
      p<0.001, OR: 62.857 95% CI 8.794-449.285 respectively) than in the controls.
      There was no significant difference in GST IIe/val frequency between the patients
      with chronic hepatitis B infection and normal carriers of hepatitis B virus,
      while GST val/val genotype was significantly more frequent in the patients with
      chronic hepatitis B infection (p=0.030, OR: 6.097, 95% CI 1.192-31.194). Both GST
      IIe/val and GST val/val genotypes were significantly more frequent in the
      patients with cirrhosis than in the normal carriers (p=0.001, OR: 12.160 95% CI
      1.618-91.360 and p<0.001, OR: 32.154, 95% CI 4.585-225.513 respectively). In
      addition, there was a significant relation between GSTP1 gene polymorphism and
      hepatitis stage. In fact, as IIe/val and val/val genotype frequencies
      significantly increased so did the stage of the disease and tendency towards
      cirrhosis (p<0.001). The difference in the GSTP1 gene polymorphism did not
      significantly differ between the healthy controls and the normal carriers of
      hepatitis B virus. Also, none of the four groups was significantly different
      concerning the presence of GSTM1 and GSTT1 gene deletions. CONCLUSIONS: The
      results of this study suggested that GSTP1-val (105) gene polymorphism could be
      associated with the course of chronic hepatitis B infection.

PMID- 19102380
TI  - Silent cirrhosis in hepatitis B virus related hepatocellular carcinoma.
AB  - BACKGROUND/AIMS: Prevalence of hepatitis B virus (HBV) related cirrhosis and
      hepatocellular carcinoma (HCC) is high in Saudi Arabia. However, thee
      relationship between these two presentations is not well studied. METHODOLOGY:
      Medical charts of 170 Saudi HBV patients (70 with HCC and 100 with cirrhosis
      without HCC) were reviewed. RESULTS: Patients with HCC at presentation were older
      compared to those with cirrhosis without HCC at presentation (60.9 y vs. 51.2 y;
      p<0.05). Right upper quadrant pain (p<0.001) and hepatic bruit (p<0.0001)
      independently predicted the presence of HCC. Cirrhosis, present in 76% of HCC
      patients, remained silent and only 4% (3 of 73) of all HCC cases had clinical
      manifest cirrhosis. Cirrhotics without HCC at presentation developed HCC at the
      rate of 0.67% per 100 person years follow up. CONCLUSIONS: Liver cirrhosis and
      HCC are distinct presentations of HBV in Saudi Arabia. Majority of patients with
      HCC at presentation have silent cirrhosis. Rate of development of HCC in patients
      with HBV related cirrhosis is low.

PMID- 19102381
TI  - Transhiatal esophagectomy for squamous cell carcinoma in liver transplant
      recipients.

PMID- 19102382
TI  - A new liver transplant priority for patients with hepatocellular carcinoma.
AB  - BACKGROUND/AIMS: Patients with hepatocellular carcinoma on the waiting list for
      liver transplantation are excluded due to causes related to liver failure and
      tumor progression. We analyze the various factors to suggest a new liver
      transplant priority. METHODOLOGY: We evaluated the outcome on the list of 309
      patients with hepatocellular carcinoma and causes of drop-out from the list were
      divided as death, "too sick" and tumor progression. The impact of model for end
      stage liver disease score, tumor stage and waiting time on the causes of drop
      outs was evaluated. RESULTS: During the study period, 197 patients had a liver
      transplantation, 50 were still on the list and the remaining 62 were removed from
      the list (28 deaths, 30 tumor progressions, and 4 "too sick"). The receiver
      operating characteristic curves analysis showed that the model for end stage
      liver disease score predicted the rate of deaths on the list at 1-year (p<0.001).
      The waiting time and the tumor stage predicted the rate of drop-outs for tumor
      progression at 1-year on the list (p<0.05). CONCLUSIONS: Patients with
      hepatocellular carcinoma on the waiting list should have priority based on their
      model for end stage liver disease score, waiting time with tumor and tumor stage.

PMID- 19102383
TI  - Prophylaxis against recurrence of HBV hepatitis after living-donor liver
      transplantation.
AB  - BACKGROUND/AIMS: Although antiviral prophylaxis with the combined high-dose
      hepatitis B immunoglobulin (HBIg) and lamivudine therapy has effectively reduced
      post-liver transplantation recurrence of hepatitis B virus infection, its use is
      limited by cost and availability. METHODOLOGY: Fourteen living-donor liver
      transplant patients were performed with the mean follow-up of the 23 months
      (range, 5 to 58 months). We examined the effectiveness of prophylaxis against
      recurrence of hepatitis B with much lower dose of HBIg. HBIg (10000 IU/day) was
      two or three times intra- and postoperatively administered and then the serum
      titers of HBIg was maintained at more than 100 IU/mL. RESULTS: Although two
      patients were preoperatively HBV-DNA positive (DNA concentrations were 4.4 and
      4.7 LGE, respectively) by a transcription-mediated amplification assay (TMA)
      method, all 14 patients postoperatively became HBV-DNA-negative and HBsAg
      negative. CONCLUSIONS: Our protocol of the combination low-dose HBIg and
      lamivudine therapy prevents the recurrence of hepatitis B and is likely to be
      more cost-effective than high-dose HBIg regimens. Further study is needed to
      develop the combination therapy of the optimal dose of HBIg and lamivudine.

PMID- 19102384
TI  - Preoperative assessment of liver metastasis originating from colorectal
      carcinoma: is super paramagnetic iron oxide particles-magnetic resonance imaging
      (SPIO-MRI) useful for screening?
AB  - BACKGROUND/AIMS: Recently, early detection of liver tumors has been possible with
      improvement of various imaging techniques, and practical selection of imaging is
      clinically necessary to distinguish metastatic liver carcinoma (MLC) from
      colorectal carcinoma. METHODOLOGY: We retrospectively examined the diagnostic
      accuracy of enhanced computed tomography (eCT) and super paramagnetic iron oxide
      particles magnetic resonance imaging (SPIO-MRI) for 110 MLC lesions in 47
      patients who underwent hepatic resection at a single Japanese cancer institute
      between 2000 and 2006. Sensitivity and positive predictive value (PPV) of both
      imaging techniques in comparison with resected specimens were analyzed. Fourteen
      cases were synchronous liver metastasis, which were resected simultaneously.
      RESULTS: On a per patient basis, both eCT and SPIO-MRI showed a sensitivity of
      85.1% (40 of 47 patients) and PPV was 100%, respectively. On a per lesion basis,
      a sensitivity of SPIO-MRI (98/110 lesions; 89%) tended to be higher than that of
      eCT (92 of 110 lesions; 84%), but not statistically different (p=0.32). PPV of
      SPIO-MRI (98 of 99 lesions; 99%) was not different from that of eCT (92 of 93;
      99%). Twelve lesions in 7 patients that were not detected by both imaging methods
      were small lesions. PPV for liver cyst and non-timorous lesions was 99% by both
      imaging methods. Two liver cysts could be clearly diagnosed by SPIO-MRI only.
      CONCLUSIONS: We found no superiority of diagnosis with SPIO-MRI, which may not be
      conceptually useful for preoperative screening for MLC from colorectal
      carcinomas. SPIO-MRI may be useful to detect non-cancerous lesions as an adjuvant
      diagnostic tool with eCT.

PMID- 19102385
TI  - Aflatoxins as a risk factor for hepatocellular carcinoma in Egypt, Mansoura
      Gastroenterology Center study.
AB  - BACKGROUND/AIMS: Aflatoxin B1 (AFB1) is an important food-borne mycotoxin. The co
      contamination of foodstuffs with this mycotoxin is well known and has been
      possibly implicated in the development of hepatocellular carcinoma in high risk
      regions around the world. This study investigates the serum aflatoxin B1 in
      patients with hepatocellular carcinoma and compares it to a control group.
      METHODOLOGY: From January 2005 to January 2006, 80 cases with hepatocellular
      carcinoma diagnosed in the Gastroenterology center, Mansoura University, Egypt
      and 20 healthy subjects used as a control group were enrolled in the study. All
      patients were evaluated for age, sex, residence, occupation, history of other
      medical diseases, anti-bilharzial treatment, blood transfusion, viral markers,
      liver functions and serum level of aflatoxin B1. RESULTS: The mean age of our
      patients was 52.88 +/- 7.27 years versus 53.17 +/- 6.78 years for the controls,
      p>0.05. The serum level of AFP1 was highly significant in HCC patients compared
      with control (32.47 +/- 92.46 versus 7.33 +/- 5.5 P<0.0001) and it was
      statistically high between 51:60-years-old (P<0.05). Males represented 82.5% of
      the patients versus 17.5% for females. AFB1 was higher in males compared with
      females (P<0.05), higher in rural residents compared with urban residents
      (P<0.05), higher in Kafer Elchek government are versus others (P<0.01) and higher
      in farmers compared with those with other occupations (P<0.05). The serum level
      of AFB1 was high among patients with a history of anti-bilharzial treatment with
      tarar emetic versus oral treatment by Brazequantil (P<0.05). Hepatitis C antibody
      was positive in 70% of the patients. The serum level of AFB1 was statistically
      high in HCV-positive patients compared with HCV-negative ones (P<0.05) but showed
      no statistical significance in HBs-positive patients compared with HBs-negative
      ones (P>0.05). The serum level of AFB1 was statistically high in Child class B
      patients compared with class A (P<0.05), high in patients with tumor size > 5 cm
      compared with tumor size < 5 cm (P<0.05), high in right lobe tumor patients
      compared with left lobe tumor (P>0.05), high in multifocal hepatoma patients
      compared with single lesion patients (P<0.05). The serum level of AFB1 showed a
      statistically significant positive correlation with serum SGPT and alpha
      fetoprotein. CONCLUSIONS: Aflatoxin B1 may play an important role in the
      occurrence of HCC in the north Nile delta area and especially in males, farmers,
      and rural residents, HCV infection, cirrhotic liver and multifocal hepatoma
      patients. Aflatoxin B1 in high concentration is associated with high incidence of
      chronic HCV, and affects hepatic parenchyma and multifocal lesions.

PMID- 19102386
TI  - Anterior approach for left-sided hepatic resection.
AB  - Complete mobilization of the liver before parenchymal transection has been a
      standard approach during major hepatectomy. This safe approach is not always
      feasible for the cases in which it is difficult to mobilize the hepatic lobe
      involved by large tumors with diaphragmatic invasion. Recently, anterior approach
      for the right-sided hepatic resection was reported as an alternative method
      without mobilization of the right lobe. The approach might be adaptive to left
      hepatectomy without mobilization of the left lobe. We demonstrated here the
      technique of anterior approach for left-sided hepatic resection to propose the
      surgical indication of this procedure.

PMID- 19102387
TI  - Hepatic hilar resection for hilar cholangiocarcinoma based on a reclassification.
AB  - Major hepatic resection for hilar cholangiocarcinoma is reportedly closely
      associated with severe postoperative complications. We performed a new limited
      resection that included total resection of the caudate lobe and anterior segment
      (ventral region of the right paramedian sector), and bile duct resection with
      hepaticojejunostomy in 3 patients with hilar cholangiocarcinoma that had not
      infiltrated the hepatic artery or portal vein. In all 3 patients, curative
      surgical resections were obtained and no serious complications were encountered.
      This new limited resection based on a reclassification of the liver may offer an
      effective procedure in limited patients with hilar cholangiocarcinoma.

PMID- 19102388
TI  - Afferent loop obstruction treated by percutaneous transhepatic insertion of an
      expandable metallic stent.
AB  - The use of expandable metallic stents (EMSs) for the management of
      gastrointestinal obstruction is increasing. Traditionally, EMSs have been used
      for the treatment of malignant esophageal and biliary strictures; however,
      several groups are examining their use in different organs, including the
      stomach, duodenum, and colon. We describe a new method for the transhepatic
      insertion of an EMS together with a double-pigtail catheter, placed from the bile
      duct to the EMS to prevent migration, in a patient with afferent loop obstruction
      caused by recurrent gastric carcinoma.

PMID- 19102389
TI  - Hepatocellular carcinoma with spontaneous regression: report of the rare case.
AB  - Spontaneous regression of a malignant tumor, including hepatocellular carcinoma,
      is extremely rare. A 78-year-old female with hepatitis B presented with a
      hepatocellular carcinoma, 3 cm in size, in the lateral segment. During her work
      up before surgery, over the period of a month, the tumor started to show
      spontaneous regression from the radiological and biochemical studies. A lateral
      segmentectomy of the liver was performed, and the pathologic study showed
      complete necrosis of the tumor with vigorous inflammatory cellular infiltration.
      The patient is now doing well without any evidence of recurrence. We herein
      report a case with hepatocellular carcinoma showing spontaneous regression, and
      review the associated literature.

PMID- 19102390
TI  - Reconstruction of the middle hepatic vein tributary with resection of the middle
      hepatic vein trunk: report of a case.
AB  - A 62-year-old man underwent right hepatectomy with resection of the middle
      hepatic vein trunk for metastatic liver cancers. Serious congestion of the caudal
      area of segment 4 occurred just after dividing the middle hepatic vein trunk. The
      reconstruction of the venous tributary from the caudal area of segment 4 to the
      inferior vena cava was performed using a saphenous vein graft of 11 cm in length.
      The congestion of the corresponding area improved just after the accomplishment
      of reconstruction, and the patient's postoperative course was uneventful. Serious
      congestion of the remnant liver observed in this case would occur rarely in the
      usual setting, because the stagnant blood flows backward to the portal branches
      or the intrahepatic venous anastomoses. In this case, the middle hepatic artery
      had been occluded by a steel coil for the treatment. Consequently, the occlusion
      of the middle hepatic artery have resulted in the serious congestion, because the
      portal branches to the caudal area of segment 4 were inflow vessels, not outflow
      ones, after division of the middle hepatic vein trunk. This is the first report
      on serious congestion of the caudal area of segment 4 and reconstruction of the
      venous tributary.

PMID- 19102391
TI  - Effective treatment for advanced hepatocellular carcinoma with portal venous
      invasion using a combination therapy of intra-arterial 5-fluorouracil and
      subcutaneous pegylated-interferon-alpha-2b.
AB  - Hepatocellular carcinoma with portal venous invasion has a poor prognosis. We
      report a case treated successfully by intra-arterial 5-fluorouracil with systemic
      pegylated-interferon-alpha-2b instead of conventional interferon-alpha. A 66-year
      old man was admitted to our hospital, and diagnosed with hepatocellular carcinoma
      with portal venous invasion. Following informed consent, he was treated with
      eight week cycles of combination chemotherapy using intra-arterial 5-fluorouracil
      (500 mg/body/day i.a., days 1-5, 8-12 continuously) and pegylated-interferon
      alpha-2b (100 microg body s.c., days 1, 8). No significant side effects were
      observed during his therapy. After 4 cycles, computed tomography scan revealed a
      partial response of tumor reduction. This is the first report of advanced
      hepatocellular carcinoma effectively treated using subcutaneous pegylated
      interferon-alpha-2b with intra-arterial 5-fluorouracil. While the conventional
      therapy of interferon-alpha with 5-fluorouracil has significant side effects, no
      significant side effects were observed in our case. The use of subcutaneous
      pegylated-interferon-alpha-2b combined with intraarterial 5-fluorouracil, may
      improve patients' quality of life.

PMID- 19102392
TI  - Spontaneous retroperitoneal massive hematoma after living-donor liver
      transplantation: an unpredictable but critical complication.
AB  - A spontaneous retroperitoneal bleeding and hematoma is among uncommon disease
      processes, which might result in sudden circulatory collapse. A 63-year-old
      female, the day after liver transplantation, had sudden circulatory collapse with
      abdominal pain. An immediate surgical management, instead of radiological
      intervention, was performed with a successful outcome. This paper provides an
      outline of the diagnosis and treatment in a case of spontaneous retroperitoneal
      hemorrhage, which developed after living-donor liver transplantation.

PMID- 19102393
TI  - Chronic autoimmune hepatitis with Epstein-Barr virus superinfection: a case
      report and review of literature.
AB  - A 66-year-old female presented with acute illness of severe hepatic dysfunction.
      She had a past history of chronic hepatitis of low disease activity. After
      admission and clinical investigation including liver biopsy, it showed an
      underlying chronic liver disease suggestive of autoimmune hepatitis (AIH) with
      early liver cirrhosis. Together with other clinical features, this patient was
      diagnosed as definite AIH type 1 by using the IAIHG (International Autoimmune
      Hepatitis Group) criteria. During this episode, superinfection by Epstein-Barr
      virus (EBV) was evidenced by positive PCR (polymerase chain reaction) test, and
      serial changes of EBV VCA IgM and IgG tests. Severe hepatic impairment was
      evidenced by markedly elevated AST level 3090 IU/L, high bilirubin level 26.4
      mg/dL, and presence of ascites. The patient gradually recovered and liver
      function improved in agreement with the decline of EBV VCA titers.
      Immunosuppressive therapy resulted in further improvement of the
      aminotransferases levels. This is an unusual case of EBV superinfection on pre
      existing AIH with early cirrhosis, which caused enhancement of the autoimmune
      disease process and resulted in severe hepatic decompensation and jaundice. We
      herein describe the case and briefly review the literature.

PMID- 19102394
TI  - Evaluation of therapeutic response to gemcitabine in pancreatic cancer.
AB  - BACKGROUND/AIMS: Due to the development of contrast-enhanced harmonic imaging,
      ultrasound can reveal more precise hemodynamic information than conventional
      angiography. In this study, the value of contrast-enhanced harmonic imaging was
      studied in the evaluation of response in treatment of pancreatic cancer.
      METHODOLOGY: Thirteen pancreatic cancer patients treated with gemcitabine were
      enrolled in this study. Contrast-enhanced harmonic ultrasonography was performed
      to evaluate the treatment response during every period of treatment. After
      intravenously injecting the contrast agent, pancreatic tumors were observed in a
      real-time and subsequently in an intermittent fashion. Findings obtained by
      contrast-enhanced harmonic imaging were compared with dynamic CT findings and
      serum tumor marker levels. RESULTS: Tumor markers were reduced by at least 50% in
      6 patients. We could not evaluate tumor size reduction rates on the B-mode US
      because the tumor margin was unclear. On the other hand, the hypovascular area
      was clearly depicted on the perfusion image of contrast-enhanced harmonic imaging
      in all patients throughout the observation period, and changes in tumor size
      could be easily evaluated. The tumor size reduction rates in these 6 cases were
      13.1 +/- 5.5% by dynamic CT and 21.1 +/- 14.1% by contrast-enhanced harmonic
      imaging. CONCLUSIONS: Contrast-enhanced harmonic imaging is useful for evaluating
      treatment response for pancreatic cancer.

PMID- 19102395
TI  - Survival benefit of pancreaticoduodenectomy in a Japanese fashion for a limited
      group of patients with pancreatic head cancer.
AB  - BACKGROUND/AIMS: To evaluate the clinical benefit of pancreaticoduodenectomy in a
      Japanese fashion for patients with pancreatic head cancer. METHODOLOGY: One
      hundred and one patients underwent pancreatectomy for pancreatic head cancer
      between 1980 and 2001. Of these, 40 patients in the extended resection (ER) group
      had an extended lymphadenectomy and neural plexus dissection as a Japanese
      fashion, while 61 patients in the conventional resection (CR) group. Tumor
      status, morbidity, mortality, survival and pattern of recurrence were
      retrospectively studied. RESULTS: The incidence of R0 operations in the ER group
      was higher than that in the CR group (p<0.01). The actuarial 5-year survival rate
      (30.6%) of patients with pStage IIA or IIB in the ER group was significantly
      higher than that (8.2%) in the CR group (p=0.04) because local recurrence (47%)
      in the CR group was higher than that (25%) in the ER group (p=0.02). In an
      immunohistochemical study of isolated tumor cells (ITCs), 13 patients (57%) with
      lymph node ITCs were included in the 23 pN0 patients. CONCLUSIONS:
      Pancreaticoduodenectomy in a Japanese fashion with an adequate extended resection
      might bring a survival benefit for patients with pStage IIA or IIB pancreatic
      head cancer.

PMID- 19102396
TI  - Efficacy of a Blake drainR on pancreatic fistula after pancreaticoduodenectomy.
AB  - BACKGROUND/AIMS: The aim of this study was to evaluate the efficacy of the Blake
      drain for the management of pancreatic fistula (PF) in comparison with the Duple
      drain. METHODOLOGY: Our study consisted of two parts: a retrospective review of
      33 patients with PF after pancreaticoduodenectomy, and a basic experiment to
      investigate the effects of the Blake drain on the management of PF in an animal
      model. RESULTS: In the clinical study, 19 patients received Blake drains (B
      group) and 14 received Duple drains (D-group). Grade C fistulas with abdominal
      bleeding developed in only 2 patients in the B-group. All the patients in the B
      group healed with conservative treatment (P<0.01). and none of them required
      percutaneous drainage or reoperation (P<0.05). In the basic experiment, no
      collections of fluid were detected around the Blake drains. When leakage
      occurred, it did not lead to abdominal abscess, and a "drain canal" formation
      linking the anastomosis with the extracorporeal orifice was demonstrated all
      along the drainage route. CONCLUSIONS: Blake drains may be efficient therapeutic
      tools in patients with grade B fistulas. The basic experiment affirms that Blake
      drains provide excellent drainage and contribute to the formation of "drain
      canals" effective in localizing and controlling PF.

PMID- 19102397
TI  - A new approach for diagnosis of hepatolithiasis: magnetic resonance
      cholangiopancreatography: potential usefulness of dehydrocholic acid (DHCA)
      administration in the evaluation of hepatolithiasis.
AB  - BACKGROUND/AIMS: The aim of this study was to investigate whether exogenous
      dehydrocholic acid (DHCA) was useful to enhance the delineation of
      hepatolithiasis. METHODOLOGY: Our study population comprised 9 patients. Magnetic
      resonance cholangiopancreatography (MRCP) was acquired before and after the
      administration of DHCA. Two different MRCP snap-shot techniques were applied:
      thick-slab two-dimensional (2D) (coronal) single shot turbo spin echo T2-weighted
      sequences and multisection thin-slab, 2D (coronal) single shot turbo spin echo T2
      weighted sequences with three-dimensional (3D) maximum intensity projection (MIP)
      post processing. RESULTS: DHCA provided a better visualization of hepatolithiasis
      in 8 of 9 cases (88.9%). CONCLUSIONS: It was suggested that administration of
      DHCA could enhance the delineation of the hepatolithiasis on MRCP images.

PMID- 19102398
TI  - Implication of interleukin 18 and intercellular adhesion molecule (ICAM)-1 in
      acute pancreatitis.
AB  - BACKGROUND/AIMS: Irrespective of the underlying etiology the immune response to
      is almost identical in severe cases of acute pancreatitis. While the triggering
      factors of acute pancreatitis are still poorly understood, cytokines are
      considered as important mediators in the pathophysiology of severe acute
      pancreatitis. However, only few studies have investigated the role of IL-18 and
      ICAM-1 in human acute pancreatitis. METHODOLOGY: Levels of IL-18 and sICAM-1 were
      studied in 87 patients with acute pancreatitis. Samples were obtained immediately
      on admission, thereafter on the third, seventh, fourteenth and twenty-first day
      after admission. Ascites or peripancreatic exudate was obtained by ultrasound
      guided fine needle aspiration in 19 patients at the day of admission. RESULTS:
      Necrotizing pancreatitis was associated with significantly elevated levels of IL
      18 and sICAM-1. Concentrations of IL-18 decreased after the first week of the
      disease in patients with non-complicated course, whereas levels remained high in
      patients with persistent multiple organ dysfunction syndrome (MODS) and infection
      of necrosis. Peak levels of sICAM-1 were observed at the time of admission with a
      subsequent decrease during the observation period. These mediators showed clear
      correlations with the disease severity, development of MODS, and infected
      necrosis. CONCLUSIONS: These proinflammatory mediators seem to be involved in the
      pathogenesis of severe acute pancreatitis, correlate with the disease severity
      and may be applied as prognostic markers.

PMID- 19102399
TI  - Serum angiotensin converting enzyme levels in pancreatic diseases.
AB  - BACKGROUND/AIMS: Recently, the existence of a local renin angiotensin system
      (RAS) in the pancreas has been demonstrated in laboratory animals as well as in
      human. It has been suggested that RAS and angiotensin converting enzyme (ACE)
      activity increase in diseases involving pancreas tissue. In the present study, we
      analyzed the relationship between serum ACE levels and pancreas disorders
      including acute and chronic pancreatitis, and pancreas adenocancer. METHODOLOGY:
      The study groups comprised 14 cases with acute pancreatitis (male/female: 5/9),
      38 chronic pancreatitis patients (male/female: 25/13) and 21 pancreas adenocancer
      cases (male/female: 11/10). The ACE activity in the sample was determined by
      comparing the sample reaction rate to that obtained with the ACE calibrator.
      RESULTS: Serum ACE levels were 38.28 +/- 23.67 U/L (10-108), 43.71 +/- 23.58 UL
      (7-120), 39.14 +/- 19.31 U/L (5-77) and 38.04 +/- 13.69 U/L for patients with
      acute pancreatitis, chronic pancreatitis, pancreas cancer and healthy controls
      respectively. Serum ACE levels were not significantly different among all groups
      (p>0.05). There was no significant difference regarding ACE levels in patients
      with metastasis and without metastasis. There was no correlation between ACE
      levels and tumor size. CONCLUSIONS: Our results showed that serum ACE levels
      increased in neither benign nor malignant pancreas diseases. However, serum ACE
      levels may not reflect the actual RAS activity because non-ACE pathways affecting
      RAS activity have been described. Further studies analyzing non-ACE pathways
      contributing to RAS activity in human pancreatic disorders are needed.

PMID- 19102400
TI  - Randomized controlled trial comparing somatostatin with octreotide in the
      prevention of complications after pancreatectomy.
AB  - BACKGROUND/AIMS: The postoperative morbidity following pancreaticoduodenectomy
      (PD) remains very high. Somatostatin or octreotide are indicated in the
      prevention of pancreatic stump-related complications. The aim of this study is to
      compare the efficacy of somatostatin and octreotide after PD. METHODOLOGY:
      Between November 2000 and December 2003 we collected prospectively clinical and
      biological data from patients with a benign or malignant pancreatic tumor
      requiring a PD. Fifty patients were randomized into two groups, 25 treated with
      somatostatin (group S) and 25 with octreotide (group O). RESULTS: There was no
      postoperative death. Complications occurred in 20 patients (40%), 11 in group S,
      9 in group O (NS). General complications occurred in 7 patients in group S, and 5
      patients in group O. Local complications related to the pancreatic stump were
      found in 4 patients in both groups. At the end of the period of administration of
      the two study drugs, 2 patients (8%) had a pancreatic fistula in group S and 3 in
      group O (12%) (p=0.52). A trend of more rapid decreased level of amylase and
      lipase concentrations in surgical drainage was observed in group S but it is not
      statistically significant (p=0.29). CONCLUSIONS: In patients requiring PD for
      pancreatic tumor, somatostatin and octreotide seem to behave similarly in the
      postoperative period.

PMID- 19102401
TI  - Protein profiling in pancreatic juice for detection of intraductal papillary
      mucinous neoplasm of the pancreas.
AB  - BACKGROUND/AIMS: Malignant intraductal papillary mucinous neoplasm of the
      pancreas (IPMN) has a very poor prognosis, and there is no useful biomarker for
      an early diagnosis at present. A biomarker is expected to allow an early
      diagnosis of IPMNs and consequently lead to an improvement of the patients'
      prognosis. Recent advances in proteomic analysis are remarkable; therefore we
      explored novel biomarkers for IPMN using Surface-Enhanced Laser Desorption and
      Ionization (SELDI) Mass Spectrometry. METHODOLOGY: We collected pancreatic juice
      samples from 33 patients with IPMNs, 54 patients with pancreatic ductal
      carcinoma, and 31 with chronic pancreatitis. We analyzed the pancreatic juice
      samples using a SELDI ProteinChip system (Ciphergen Biosystems, Fremont, CA).
      RESULTS: We identified a 6240-Da peak whose expression in pancreatic juice from
      patients with IPMNs was significantly higher compared with that in other
      pancreatic diseases (P<0.01). This 6240-Da protein was partially purified and was
      identified as pancreatic secretory trypsin inhibitor (PSTI) by amino acid
      sequencing. The pancreatic juice PSTI levels, as measured by radioimmunoassay,
      were significantly higher in the IPMN group than in the other groups (P<0.001).
      When the diagnostic cutoff value of PSTI in pancreatic juice was set at 25000
      ng/mL, the positive predictive value, negative predictive value, sensitivity, and
      specificity were respectively 89%, 83%, 48%, and 98%. CONCLUSIONS: PSTI levels of
      pancreatic juice in patients with IPMN were significantly higher than those in
      patients with other pancreatic diseases. The PSTI level in pancreatic juice may
      be useful for the diagnosis of IPMN.

PMID- 19102402
TI  - Combined pancreatic resection and pancreatic duct-navigation surgery for multiple
      lesions of the pancreas: intraductal papillary mucinous neoplasm of the pancreas
      concomitant with ductal carcinoma of the pancreas.
AB  - When a branch-type IPMN of the uncinate process is concomitant with ductal
      carcinoma of the body of the pancreas, total pancreatectomy may be recommended.
      However, a decrease in quality of life becomes a serious problem after total
      pancreatectomy because of the abolition of endocrine and exocrine pancreatic
      function. We proposed the combined resection, which consists of resection of the
      uncinate process of the pancreas with distal pancreatectomy. This surgical
      procedure of combined resection is most suitable for preservation of the
      pancreatic functions. In addition, we recommend the pancreatic duct-navigation
      surgery to enable us to prevent injury to the main pancreatic duct, and to
      dissect at the optimal cutting point of the pancreatic branch duct.

PMID- 19102403
TI  - Successful treatment for pancreatic injury presented with pancreatic ascites 2
      months after a blunt abdominal trauma.
AB  - We report our experience of surgical treatment for a patient with pancreatic
      injury, who presented with pancreatic ascites 2 months after a blunt abdominal
      trauma. A 20-year-old woman was admitted to our hospital due to massive ascites
      and dehydration. This patient was diagnosed as having pancreatic ascites caused
      by the rupture of pancreatic pseudocyst, and the pseudocyst seemed to have caused
      by the trauma that she sustained 2 months before. As non-surgical treatment did
      not bring about an improvement of the patient status, she underwent
      cystogastrostomy. Postoperative course was uneventful and the patient was
      discharged on the 25th postoperative day. The patient is doing well 7 years after
      surgery without any signs of pancreatic pseudocyst or diabetes. A case of
      pancreatic ascites presenting after a significant time period following initial
      abdominal trauma has not been reported.

PMID- 19102404
TI  - Partial splenic embolization: 12-month hematological effects and complications.
AB  - BACKGROUND/AIMS: To investigate the hematological effects and immediate
      postoperative complications of partial splenic embolization (PSE) in patients
      with liver cirrhosis. METHODOLOGY: Record of liver cirrhosis patients with
      thrombocytopenia and leukopenia in whom PSE was performed between June 1995 and
      June 2005 were reviewed. Peripheral blood counts were evaluated at baseline, at 1
      week, and at months 1, 3, 6, and 12 months post-PSE and clinically significant
      complications were recorded. RESULTS: In the twenty patients who underwent PSE,
      significant improvements in thrombocyte and leukocyte levels were noted at all
      time points compared to baseline levels up to one year following PSE (P<0.01).
      The complication rate was 100% because all patients experienced fever and
      abdominal pain. Only 7 patients (35%) experienced additional, mild post
      embolization complications, and only 2 (10%) experienced serious complications.
      The mortality rate in this study was 0%. CONCLUSIONS: PSE significantly improved
      thrombocytopenia and leukopenia. These results support the contention that PSE is
      effective and safe, and should be employed more widely in the management of
      thrombocytopenia in patients with liver cirrhosis, particularly higher-risk
      patients that may not be candidates for surgical splenectomy. Further studies
      evaluating risk factors, criteria for patient selection, and target embolization
      area are warranted.

PMID- 19102405
TI  - Effect of gelatinization on gastric emptying and absorption.
AB  - BACKGROUND/AIMS: For gastrointestinal functional analysis such as gastric
      emptying tests, either a liquid or solid meal is used as a test meal. Only a few
      studies have compared meal characteristics, such as liquid and solid. No previous
      study has compared test meals that had the same composition but different
      properties. The aim of this study was to compare the gastric emptying and
      absorption obtained by 13C-breath test after ingestion of liquid or gelatinized
      liquid nutrients. METHODOLOGY: Ten healthy volunteers were studied four times,
      with 2-week intervals. For the test meal, 200 mL of liquid meals (200 kcal) and
      gelatinized liquid meals were used. Gelatinized liquid nutrients were prepared by
      mixing 6 g, 12 g and 18 g of Natural psyllium husk with 200 mL of liquid meals.
      Breath samples were collected for four hours. Gastric emptying were expressed as
      the time of peak excretion, absorption were expressed as the area under the 13CO2
      curve up to the time of peak excretion. RESULTS: Gastric emptying times were
      54.5, 54.5, 81.7 and 93.3 min. Absorption was 20.8, 20.9, 27.8 and 29.8% dose.
      CONCLUSIONS: Gelatinization influences gastric emptying, but does not influence
      absorption. Gelatinized liquid meals may be useful for a substitute for solid
      meals on gastrointestinal functional analysis.

PMID- 19102406
TI  - Phase II study of weekly paclitaxel and cisplatin combination therapy for
      advanced or recurrent gastric cancer.
AB  - BACKGROUND/AIMS: This study was performed to assess the efficacy and safety of
      weekly paclitaxel and cisplatin combination chemotherapy in patients with
      advanced or recurrent gastric cancer. METHODOLOGY: Patients with advanced or
      recurrent gastric cancer were required to have ECOG performance status of 0 to 2,
      to be over 20 years of age, and to have adequate organ function. Paclitaxel 80
      mg/m2 was administered intravenous over 1.5 h, followed by cisplatin 25 mg/m2 on
      day 1, 8 and 15 every 4 weeks. RESULTS: All of the 52 patients enrolled, 49
      patients were eligible. One patient had complete response. Nineteen had partial
      response, 13 had stable disease, 8 had progressive disease and 8 had not been
      evaluated. The median progression-free survival time was 166.5 days and median
      survival time was 323 days. The most common grade 3 to 4 hematological toxicies
      were leucopenia (14.3%), neutropenia (32.7%), and anemia (16.3%). The most common
      grade 3 non-hematological toxicities included anorexia (6.1%), nausea (4.1%),
      vomiting (2.0%) and fatigue (2.0%). No grade 4 non-hematological toxicities were
      reported. CONCLUSIONS: Combination chemotherapy of weekly paclitaxel and
      cisplatin was highly active and well tolerated in patients with advanced or
      recurrent gastric cancer.

PMID- 19102407
TI  - Does Roux-en Y reconstruction with jejunal pouch after total gastrectomy prevent
      complications of postgastrectomy?
AB  - BACKGROUND/AIMS: To evaluate the efficacy of a jejunal pouch after a total
      gastrectomy with Roux-en Y reconstruction. METHODOLOGY: Thirty patients with
      gastric cancer who had a total gastrectomy as a radical operation and had no
      recurrence were enrolled in this study. The jejunal pouch was added to Roux-en Y
      reconstruction in 15 patients (J-pouch group) and was not added in the other 15
      patients (Roux en-Y group). A questionnaire survey which consisted of dietary
      intake, postprandial abdominal complaints and body weight, blood examination
      (hemoglobin, total protein, albumin), were conducted. The 99mTc-DTPA with semi
      liquid diet emptying test and the manometry in the jejunal pouch were evaluated
      in 12, 2 of the J-pouch group, respectively. RESULTS: There were no significant
      differences between the two groups in the questionnaire survey and blood
      examination. The half emptying time (T1/2) of 99mTc-DTPA was over 60 minutes in 9
      of the 12 J-pouch group. The manometric study did not reveal the effective
      contraction of the jejunal pouch. Bypass operation was necessary due to marked
      delay of emptying in the jejunal pouch for one patient in the J-pouch group.
      CONCLUSIONS: The advantage of adding a jejunal pouch to Roux en-Y reconstruction
      was not proven in this study.

PMID- 19102408
TI  - Incidence of gastric cancer in the remnant stomach after proximal gastrectomy.
AB  - BACKGROUND/AIMS: Gastric cancer in the remnant stomach after proximal gastrectomy
      has not been studied in detail. The aim of this study was to clarify the
      incidence of this type of cancer. METHODOLOGY: From 478 cases of radical proximal
      gastrectomy followed prospectively, those that developed gastric cancer in the
      remnant stomach were identified. The incidence of gastric cancer in the remnant
      stomach in the cohort was compared with the expected incidence of gastric cancer
      in the general population. RESULTS: Gastric cancer in the remnant stomach
      occurred in 8 (6 males, 2 females) of 478 patients (1.7%). The duration from
      primary gastrectomy to gastric cancer in the remnant stomach detection was over
      10 years in 3 cases. In males, the rate of the incidence of gastric cancer in the
      remnant stomach was lower than the expected incidence for all durations. In
      females, the rate was also low, but appeared slightly elevated from 6 to 10 years
      and from 16 to 20 years after the primary gastrectomy. CONCLUSIONS: The incidence
      of proximal gastrectomy after proximal gastrectomy is not high, and the risk in
      males is especially low. However, proximal gastrectomy may develop over 10 years
      after surgery, and long-term follow-up is essential.

PMID- 19102409
TI  - Artificial neural network-based study can predict gastric cancer staging.
AB  - BACKGROUND/AIMS: Primary gastric cancer is a multi-factorial disease comprising
      many low-penetrance clinicopathological factors and genetic predisposition.
      Preoperative prediction of tumor staging can be made by artificial neural network
      (ANN)-based study using clinic-pathological datasets and genetic susceptibility
      testing. METHODOLOGY: A hospital-based, retrospective, randomized control study
      was conducted for 121 patients who had recently developed primary gastric cancer.
      Clinical data and pathological findings were collected and genetic polymorphisms
      of candidate genes were evaluated. ANN-based study was conducted to predict tumor
      staging and to evaluate the relative impact of each factor. RESULTS: The best
      training method was the Quick method, which had an accuracy of 81.82%. The most
      important factors associated with tumor staging were age and polymorphisms of
      genes p21, IL-1, IL-4 and p53. CONCLUSIONS: Analysis of genetic polymorphisms of
      candidate genes by ANN using clinicopathological datasets is a promising method
      for predicting human gastric cancer staging. This strategy can identify the
      important genetic, clinical and pathological factors, determine their relative
      impact, and aid in the development of a prognostic staging system that is useful
      in individualized patient care.

PMID- 19102410
TI  - Changes of nutritional status after distal gastrectomy in patients with gastric
      cancer.
AB  - BACKGROUND/AIMS: In Japan, distal gastrectomy is the most common operation
      performed to treat gastric cancer. However, this procedure often leads to
      postoperative problems such as weight loss. METHODOLOGY: We assessed the changes
      of nutritional status early after operation and the associations of the
      postoperative body weight (as a percentage of the preoperative weight) and
      background factors in patients who underwent distal gastrectomy. We measured the
      changes of nutritional indices (mean body weight, TSF, AMC and Alb) and nutrition
      intake on the day before operation (before operation), before postoperative
      resumption of oral intake (before oral intake), and on the fifth day of a soft
      rice porridge diet (after soft rice). Background factors included gender, age,
      preoperative BMI and preoperative exercise. RESULTS: Mean body weight, TSF, and
      AMC significantly decreased from before operation, to the day before oral intake
      and to the day after soft rice. The postoperative body weight was not associated
      with the gender, age, or preoperative BMI. The frequency of regular preoperative
      exercise was associated with the postoperative body weight. The total daily
      calorie intake was 1,664 kcal (before operation), 398 kcal (before oral intake),
      and 949 kcal (after soft rice). CONCLUSIONS: To conclude, nutritional status
      changes significantly after distal gastrectomy. Early nutrition intervention may
      be needed in patients who undergo distal gastrectomy for gastric cancer.

PMID- 19102411
TI  - Serum cytokine changes after gastric resection or gastrectomy for gastric cancer.
AB  - BACKGROUND/AIMS: Although essential for postoperative recovery, excessive
      surgical stress response leads to higher rate of serious postoperative
      complications, such as sepsis and multiple organ disorder syndrome. Exact
      regulation of surgical stress response is not yet known. Still, our ability to
      modify surgical stress response severity has led to diminished postoperative
      morbidity and mortality rates and development of fast-track surgery. In this
      study we tried to further clarify the roles of several cytokines in surgical
      stress response regulation. METHODOLOGY: We measured leukocyte count and serum
      concentrations of C-reactive protein, IL-2, IL-6, IL-10, TNF-alpha, IFN-gamma and
      cortisol in patients undergoing gastrectomy or gastric resection for gastric
      cancer. Blood samples were collected preoperatively, 3 hours, 24 hours and 48
      hours postoperatively. We also grouped our patients according to operation type
      and duration and then compared measured values between groups. RESULTS: Elevated
      postoperative leukocyte count and serum concentrations of IL-4, IL-6, IL-10 and
      cortisol were measured, all peaking at 3 hours postoperatively. Also, serum IL-6
      concentration was higher after longer operations, and leukocyte count was higher
      after gastrectomy. CONCLUSIONS: The synchronicity of postoperative elevation of
      IL-4, IL-6 and IL-10 concentrations, each having different role in surgical
      stress response regulation, might indicate that, in order to determine surgical
      stress response severity, several cytokines should be measured simultaneously.

PMID- 19102412
TI  - Strong association of lymph node metastasis with intraperitoneal free cancer cell
      (IFCC) in advanced gastric cancer.
AB  - BACKGROUND/AIMS: Advanced gastric cancer is a disease with dismal prognosis,
      which is mainly characterized by the emerging intraperitoneal free gastric cancer
      cells (IFCC). Our interest is to elucidate a causative phenotype linking to IFCC.
      METHODOLOGY: Two hundred and sixty-nine resected gastric cancer patients examined
      for IFCC were enrolled at the Kitasato University Hospital to evaluate the
      clinical significance of the interaction between IFCC and other tumor phenotypes.
      RESULTS: IFCC was not found in the 22 early gastric cancers, and we were thus
      restricted to evaluate the remaining gastric cancers beyond the muscuralis
      propria (MP). Among the 247 advanced gastric cancer patients, IFCC was a potent
      univariate prognostic factor (p<0.0001) as well as lymph node metastasis
      (P<0.0001), depth of invasion (P=0.0015), and age (P=0.009). IFCC affects poor
      prognosis more strongly in the modest node disease (n0/n1) than in the severe
      node disease (n2/n3/M), even after considering D2 dissection. In the modest node
      disease, multivariate prognostic analysis revealed IFCC as an independent
      prognostic factor, and lymph node metastasis (n1 against n0 disease) is the only
      independent predictive tumor factor of IFCC in the logistic regression analysis.
      As a result, we finally noticed that lymph node metastasis exists in almost
      advanced gastric cancer with IFCC, while IFCC was hardly detected unless lymph
      node metastasis exists. CONCLUSIONS: IFCC could be rather strongly associated
      with lymph node metastasis than depth of invasion in advanced gastric cancer, and
      transition from the node disease to the peritoneal disease plays a critical role
      in gastric cancer progression affecting dismal prognosis. Its regulation may be
      an optimal therapeutic target of advanced gastric cancer.

PMID- 19102413
TI  - Interleukin-1 gene family polymorphisms from paraffin-embedded archival tissue of
      Chinese patients with gastric ulcer and gastric cancer.
AB  - BACKGROUND/AIMS: Polymorphisms of the interleukin (IL)-1 gene family have been
      associated with increased risk of gastric ulcer and gastric cancer. The aim of
      this study was to determine the relationship between single nucleotide
      polymorphisms (SNPs) in the IL-1 gene family in archival tissue of gastric ulcer
      and gastric cancer to enable further large scale population investigation in the
      Chinese Han population from the Wuhan Hubei region. METHODOLOGY: DNA was
      extracted from archival paraffin-embedded tissue blocks of 53 cases with gastric
      cancer (22 intestinal type, 29 diffuse type, and 2 mixed type) and 34 cases with
      gastric ulcer. The tissue specimens had been routinely fixed in unbuffered 10%
      formalin. Genotyping of SNPs IL-1B T-31C, IL-1B C+3954T and IL-1RN T+2018C was
      performed using Taqman real-time PCR allelic discrimination technology. RESULTS:
      The frequency of genotype IL-1B-31C/C seems to be increased in patients with
      gastric cancer (32.1%) when compared to patients with gastric ulcer (11.8%)
      (P<0.05). Allele IL-1B+3954T/T was not be found in patients with gastric cancer
      and gastric ulcer. The quality of genomic DNA extracted from the paraffin
      embedded, unbuffered formalinfixed tissue blocks did enable reliable genotyping
      of all samples. CONCLUSIONS: IL-1B-31C/C may be associated with gastric cancer in
      patients of Chinese Han population. The genotype of IL-1B3954 T/T may protect
      against gastric cancer and gastric ulcer in Chinese Han population. Unbuffered
      formalin-fixed, paraffin-embedded gastric tissue from Chinese patients with
      gastric ulcer and gastric cancer is a valuable source of DNA, suitable for large
      scale investigation.

PMID- 19102414
TI  - The discrepancy in thymidylate synthase and dihydropyrimidine dehydrogenase
      expression depending on measurement methodologies in stage 4 gastric cancer.
AB  - BACKGROUND/AIMS: Thymidylate synthase (TS) and dihydropyrimidine dehydrogenase
      (DPD) are reported to be a major determinant of variations in the sensitivity for
      fluoropyrimidines in gastric cancer. The aim of this study was to investigate
      whether there is a discrepancy in the TS and DPD expression depending on
      measuring method. METHODOLOGY: The protein levels and mRNA level of TS and DPD
      were estimated in primary gastric cancer tissue specimens after a non-curative
      resection. The protein levels were determined by ELISA from frozen tissue
      specimens. The gene expressions were measured using real-time reverse
      transcriptional polymerase chain reaction (RT-PCR). For the extraction of RNA,
      laser-captured microdissection (LCM) was performed in formalin-fixed paraffin
      embedded (FFPE) specimens. RESULTS: There was no correlation between the protein
      levels and mRNA levels of TS and DPD. The protein levels and mRNA expression
      levels were not correlated with survival. High levels of TS mRNA showed a trend
      toward reduced survival (p=0.074). CONCLUSIONS: The discrepancy in TS and DPD
      expressions depending on the measurement methodologies utilized should thus be
      emphasized in these far advanced gastric cancer patients.

PMID- 19102416
TI  - Clinicopathological significance of urokinase-type plasminogen activator
      genotypes in gastric cancer.
AB  - BACKGROUND/AIMS: The roles of urokinase-type plasminogen activator (uPA)
      expression in tumor occurrence, invasion and prognosis have been established.
      However, how uPA genetic polymorphisms influence the occurrence and outcome of
      tumors is not as clear. METHODOLOGY: We conducted a case-control study based on
      previously stored peripheral blood samples from 237 gastric cancer patients and
      242 healthy controls. uPA exon 6 and intron 7 genotypes were determined by direct
      DNA sequencing. Logistic regression analyses and Cox proportional hazards
      analyses were used to evaluate the associations between polymorphisms and gastric
      cancer susceptibility, clinicopathological features, and survival. RESULTS: uPA
      exon 6 C/T and intron 7 T/C polymorphisms did not correlate well with gastric
      cancer susceptibility. uPA exon 6 T/C and T/T genotypes were associated with
      venous invasion and lymphatic invasion, but not with stage, serosal invasion or
      lymph node metastasis. uPA intron 7 T/C polymorphism did not correlate well with
      invasive phenotype of gastric cancer. On Cox proportional hazards analyses, uPA
      exon 6 and intron 7 polymorphisms were not independent prognostic factors for
      survival. CONCLUSIONS: uPA exon 6 C/T polymorphism is associated with invasive
      phenotype of gastric cancer, but not with susceptibility or survival of gastric
      cancer. uPA intron 7 is a silent polymorphism.

PMID- 19102415
TI  - The influence of Helicobacter pylori patients' treatment on MUC 1 content in
      gastric juice.
AB  - BACKGROUND/AIMS: Helicobacter pylori that resides in the gastric mucus layer is
      the major etiological factor in gastritis, gastric ulcers and carcinomas. Among
      others, carbohydrate structures of MUC 1 mucin are also considered by some
      authors as being important in the mechanism of infection. The main aim of our
      study was to establish whether Helicobacter pylori treatment has any influence on
      the level of soluble form of MUC 1 mucin in gastric juice. METHODOLOGY: We
      examined two groups of Helicobacter pylori infected patients. The first group was
      treated with omeprazole (at the end of the therapy the bacterium was still
      present). The second group was treated with omeprazole and antibiotics, and the
      bacterium eradication was confirmed. MUC 1 mucin was determined by Western
      blotting technique. RESULTS: Before the therapy, the level of MUC 1 was found to
      be low in almost all cases, while at the end of the treatment in both groups of
      patients an increase of MUC 1 mucin was observed. CONCLUSIONS: Our results can
      confirm the thesis that Helicobacter pylori inhibits the expression of MUC 1
      mucin on cell membranes.

PMID- 19102417
TI  - Neoadjuvant chemotherapy versus surgery alone for locally advanced gastric
      cancer: a retrospective comparative study.
AB  - BACKGROUND/AIMS: Preoperative chemotherapy is considered an effective treatment
      option for patients with gastric cancer. We retrospectively evaluated neoadjuvant
      chemotherapy with oxaliplatin, leucovorin and 5-flurouracil (OLF) in patients
      with locally advanced gastric cancer to determine its feasibility, as well as
      impact on the curative resection rate and patients' survival. METHODOLOGY: A
      total of 87 patients with locally advanced gastric cancer that underwent
      preoperative chemotherapy combined with surgery or surgery alone were randomly
      matched according to the clinical TNM stage. The clinical responses to
      chemotherapy were assessed. The curative rate, postoperative complications and
      patients' survival between both groups were compared. RESULTS: The two groups
      were well matched. Complete or partial response was observed in 51.7% (15/29) of
      patients in the OLF group, and three (10.3%) of them had complete pathologic
      response. The curative resection rates were 89.7% in the OLF group and 77.6% in
      the surgery alone group. The postoperative complications were equal for both
      groups. The mean survival is 20.6 months in the OLF group vs. 19.9 months in the
      surgery alone group (p=0.02). CONCLUSIONS: Neoadjuvant chemotherapy using OLF
      combination is active in gastric cancer and the toxicity level is acceptable.
      This treatment improves the curative resection rate and patients' survival in
      locally advanced gastric cancer.

PMID- 19102419
TI  - Effects of body positions on gastric emptying with enteral nutrition: a crossover
      study using a continuous real time 13C breath test (BreathID system).
AB  - BACKGROUND/AIMS: The aim of this study was to determine whether there was a
      correlation between body positions and gastric emptying, using a novel non
      invasive technique for measuring gastric emptying with a continuous real time 13C
      breath test (BreathID system). METHODOLOGY: Ten healthy male volunteers
      participated in this randomized, two-way crossover study. On both occasions, the
      13C breath test was performed for 4 hours using the BreathID system with a liquid
      meal (200 kcal per 200 mL) containing 100 mg 13C-acetic acid. Subjects were
      randomly assigned to sit comfortable (the sitting position) or to lie supine (the
      lying position). RESULTS: In the lying position, T 1/2 and T lag were
      significantly delayed. The gastric emptying coefficient was also decreased in
      lying position. CONCLUSIONS: This study showed that gastric emptying following a
      liquid meal was significantly delayed in the lying position compared to the
      sitting position, suggesting the potential use of these findings in the clinical
      setting for patients receiving enteral nutrition via the stomach.

PMID- 19102418
TI  - Gastric surgery is not a risk factor for the development or progression of
      Barrett's epithelium.
AB  - BACKGROUND/AIMS: Barrett's epithelium is currently believed to be related to acid
      gastroesophageal reflux. The aim was to determine the role of pancreatic-biliary
      reflux in the genesis of Barrett's epithelium. METHODOLOGY: The study population
      comprised 1055 cases (606 men and 449 women; median age, 67 years) who had
      undergone an upper endoscopy at the Gastroenterology Division of Yokohama City
      University Hospital between August 2005 and July 2006. The study population was
      composed of 869 cases with intact stomachs and 186 cases with distal
      gastrectomies. The presence and the progression of Barrett's epithelium were
      diagnosed based on the Prague C & M Criteria. The correlations of clinical
      factors, including distal-gastrectomy, with the presence and the progression of
      Barrett's epithelium were examined. RESULTS: The study demonstrated that 42.2% of
      the total population was diagnosed to have Barrett's epithelium and, in 12.6% of
      the cases with Barrett's epithelium, the progression of Barrett's epithelium was
      observed during the median 72 month followup. A distal gastrectomy was not
      significantly correlated with either the incidence or progression of Barrett's
      epithelium. CONCLUSIONS: This lack of association between gastric surgery and
      Barrett's epithelium suggests that pancreatic-biliary reflux with limited acid is
      not sufficient for the genesis of Barrett's epithelium.

PMID- 19102420
TI  - Laparoscopically-assisted palliative total gastrectomy in patients with stage IV
      or metastatic gastric cancer: is it worthwhile?
AB  - BACKGROUND/AIMS: Conventional open total gastrectomy in patients with IV stage or
      metastatic gastric carcinoma in the middle or upper third of the stomach is under
      controversy due to its poor prognosis and its surgical complexity. Based on
      advances in laparoscopic equipment, techniques, and ongoing experience in
      laparoscopically- assisted D2 total gastrectomy, laparoscopically-assisted
      noncurative total gastrectomy was performed in patients with stage IV or
      metastatic gastric carcinoma in the middle or upper third of the stomach who
      suffered from local gastric bleeding, pain, obstruction symptoms refractory to
      other therapies at our institution. The purpose of the current study was to
      determine feasibility of laparoscopically-assisted noncurative total gastrectomy
      in patients with stage IV disease or metastatic gastric cancer. METHODOLOGY:
      Between July 2005 and Sep 2007 in our institution, 43 patients with stage IV
      disease or metastatic gastric carcinoma in the middle or upper third of the
      stomach who suffered from local gastric bleeding, pain, obstruction refractory to
      other therapies underwent laparoscopically-assisted noncurative total
      gastrectomy. Stomach was dissected and the first part of the duodenum was
      transected laparoscopically. Because of extensive involvement of adjacent
      tissues, final dissection was performed extracorporeally by a small laparotomy
      incision under the xyphoid (5-7 cm) for removal of specimen and anastomosis.
      Clinical data of the procedure was analyzed. RESULTS: None of 43 patients was
      converted to laparotomy and no operative mortality was observed. Final dissection
      of involvement was extracorporeally performed by a small laparotomy incision in
      18 patients with extensive involvement of adjacent tissues. Postoperative
      complication occurred in 4 cases (9%), 1 minor duodenal stump leak, 3 wound
      infection. The mean operative time was 245 +/- 81 min, operative blood loss was
      163 +/- 131 mL. Time of ambulation and first flatus were 2.6 +/- 1.3 and 3.3 +/-
      1.0 days after surgery respectively. All patients uneventfully recovered after
      surgery. Mean hospital stay was 8.8 +/- 3.5 days. All preoperative symptoms
      resolved. Mean survival time was 8.9 +/- 3.2 months, 5 patients still are alive
      to present within fellow-up of 6-15 months. CONCLUSIONS: Laparoscopically
      assisted noncurative total gastrectomy in patients with stage IV or metastatic
      gastric cancer is considered to be a safe and feasible approach. Laparoscopically
      assisted palliative total gastrectomy can be performed to obtain better quality
      of life in patients with gastric cancer who suffered from local gastric bleeding,
      pain, obstruction symptoms refractory to other therapies.

PMID- 19102421
TI  - Prognostic significance of peritoneal washing cytology in patients with
      potentially resectable gastric cancer.
AB  - BACKGROUND/AIMS: The prognostic value of cytological examination of
      intraoperative washings in potentially resectable gastric cancer is
      controversial. METHODOLOGY: Between February 1993 and August 2001,
      clinicopathological features and surgical outcome of 26 consecutive patients with
      gastric cancer with positive cytological findings of peritoneal washings without
      peritoneal dissemination were retrospectively analyzed. RESULTS: The overall 1,
      2, 3-year survival rates for 26 patients were 69%, 35%, and 0%, respectively. The
      median survival was 17.5 months. The median survival of patients with curative
      resection (n=16) and non-curative resection (n=10) was 19 months and 12.5 months,
      respectively. There was no significant difference in survival between curative
      resection and non-curative resection (p=0.10). Recurrent disease frequently
      occurred as peritoneal dissemination (69%). No patient survived for more than 34
      months. CONCLUSIONS: Aggressive surgical resections do not provide any survival
      benefit for gastric cancer with positive cytological findings of peritoneal
      washings even in the absence of peritoneal dissemination.

PMID- 19102422
TI  - Expression of S100A4, E-cadherin, alpha- and beta-catenin in gastric
      adenocarcinoma.
AB  - BACKGROUND/AIMS: This investigation aimed to elucidate the expression patterns of
      S100A4 and adhesion molecules in gastric carcinoma and to estimate their
      correlation with clinicopathologic parameters. METHODOLOGY: The expression of
      S100A4, E-cadherin, alpha- and beta-catenin was studied in 251 gastric carcinoma
      specimens through immunohistochemical staining. RESULTS: The positive expression
      of S100A4 was significantly associated with advanced gastric cancer, higher pTNM
      stage, and poorer survival rates, especially when present in nuclear staining.
      The reduced expression of adhesion molecules was significantly associated with
      diffuse type of gastric cancer. The reduced expression of beta-catenin was
      significantly associated with lymph node metastasis, especially in early gastric
      cancer. The coexpression status of S100A4-positive and reduced beta-catenin was
      significantly associated with larger tumor size, advanced tumor depth, and higher
      pTNM stage. CONCLUSIONS: S100A4 and adhesion molecule expression may be a useful
      prognostic marker for individual gastric cancer patients.

PMID- 19102423
TI  - Serotonin-2A receptor gene T102C polymorphism in patients with dyspeptic
      symptoms.
AB  - BACKGROUND/AIMS: The role of genetics in the susceptibility to functional
      dyspepsia (FD) is unclear. Serotonin (5-HT) is expressed in gastro-intestinal
      tract and modulates the sensory-motor functions in the digestive tract. Genetic
      association has been reported between C102T polymorphism in the gene encoding 5
      HT 2A receptor (5HTR2A) and various diseases. We aimed to clarify the association
      between 5HTR2A C102T polymorphism and dyspeptic symptom in a Japanese population.
      METHODOLOGY: 91 dyspeptics and 93 non-dyspeptic subjects enrolled in this study.
      Dyspeptic symptoms were divided into 9 categories. 5HTR2A gene T102C polymorphism
      was determined by polymerase chain reaction-restriction fragment length
      polymorphism. RESULTS: In the non-dyspeptics, the 5HTR2A geno type distribution
      was 21TT (22.6%), 50TC (53.8%), and 22CC (23.6%). Meanwhile, the 5HTR2A genotype
      distribution in dyspeptics was 30 TT (33.0%), 40 TC (43.9%), and 21 CC (23.1%).
      There was no significant difference between the two groups in the genotype
      distribution. We did not find any association between 5HTR2A genotypes and
      dyspeptic patients in different gender and H. pylori infection status. Also, no
      correlation was found between 5HTR2A polymorphism and any of the 9 different
      dyspeptic symptoms. CONCLUSIONS: Our results suggest that 5HTR2A polymorphism is
      unlikely to be associated with susceptibility of dyspeptic symptoms. The role of
      genetics to the development of dyspepsia needs further evaluation.

PMID- 19102424
TI  - Clinicopathologic characteristics of gastrointestinal stromal tumor of the
      stomach.
AB  - BACKGROUND/AIMS: This study was undertaken to investigate a surgical role in
      treating gastrointestinal stromal tumors (GISTs) of the stomach and to find their
      behavior and prognostic factors. METHODOLOGY: The clinicopathologic results of
      112 patients with gastric GISTs who underwent surgery from December 1999 to
      August 2006 were reviewed. RESULTS: Forty (35.7%) patients had no symptoms. Of a
      total of 112 patients, curative resections were performed on 105 (93.8%). There
      were 41 (36.6%) high-risk patients. The mean follow-up period was 34.3 months (1
      82 months) and there were two deaths. Six (5.7%) of the 105 patients who received
      curative resections had recurrences and all recurrences occurred only in high
      risk patients. Univariate analysis showed that tumor size and mitotic count were
      prognostic for disease-free survival of GIST patients (p=0.0004 and p<0.0001,
      respectively), but multivariate analysis identified mitotic count as the only
      prognostic factor for disease-free survival of GIST patients (p=0.039).
      CONCLUSIONS: The curative resection rate was high in GISTs of the stomach and
      they were treated using various surgical procedures. Patient survival after
      curative resection was good. Mitotic count was the independent prognostic factor
      for disease-free survival and only high-risk patients had recurrences.

PMID- 19102425
TI  - Characteristics of gastric cancer in patients over 80-years-old.
AB  - BACKGROUND/AIMS: The number of elderly gastric cancer patients undergoing surgery
      is rapidly increasing because of the current aging society. To determine an
      effective surgical treatment method, the clinicopathological characteristics of
      such patients should therefore be clarified. METHODOLOGY: Between 1979 and 2005,
      2010 patients with gastric cancer underwent curative surgery in our institute.
      Clinicopathological characteristics of 109 patients in the elderly group (> or =
      80-years-old) were compared with those of 1901 patients in the young group (< 80
      years-old). RESULTS: In the elderly group, cancers of the lower third of the
      stomach and differentiated types, and less-invasive surgery were common. The 5
      year survival rate specific to gastric cancer was not significantly different
      between groups, but the overall 5-year survival rate including causes other than
      gastric cancer was significantly different (p<0.01) at 82% in the elderly group
      and 67% in the young group. CONCLUSIONS: In the medical care of elderly gastric
      cancer patients, it is necessary to accurately determine the specific
      clinicopathological characteristics, and subsequently, an effective surgical
      treatment method.

PMID- 19102426
TI  - Prognostic significance of intragastric pressure for the occurrence of aspiration
      pneumonia in the patients with percutaneous endoscopic gastrostomy (PEG).
AB  - BACKGROUND/AIMS: Patients who have undergone a percutaneous endoscopic
      gastrostomy have been increasing. However, complications in serious patients are
      encountered more frequently. We attempted to examine the simple and new technique
      for the purpose of preventing complications in percutaneous endoscopic
      gastrostomy patients. By using our method of measuring of the intragastric
      pressure during the fasting period, the aspiration pneumonia of percutaneous
      endoscopic gastrostomy patient could be estimated. METHODOLOGY: From January 2003
      to December 2005, one hundred and thirty-two consecutive patients were examined.
      The intragastric pressure is measured by using a percutaneous endoscopic
      gastrostomy tube. This method is referenced as the technique for measuring the
      intra-abdominal pressure which is measured in the case of the abdominal
      compartment syndrome and the central venous pressure. RESULTS: The mean
      intragastric pressure of patients with complicated pneumonia was 10.4 +/- 7.1 cm
      H2O, and 4.7 +/- 4.5 cm H2O with non-complicated pneumonia (p=0.0001). In cases
      of the patients in whom the tube immediately becomes dirty, the mean intragastric
      pressure was higher than in clean cases (p=0.0005). CONCLUSIONS: There is a
      relationship between the intragastric pressure and the incidence of complications
      such as aspiration pneumonia. Our simple and easy technique can estimate the
      aspiration pneumonia.

PMID- 19102427
TI  - Efficacy of S-1 for gastric cancer patients with positive peritoneal lavage
      cytology.
AB  - BACKGROUND/AIMS: Positive peritoneal lavage cytology (PLC) is a strong predictor
      of subsequent frank peritoneal dissemination. The prognosis for patients with
      positive PLC is as poor as with macroscopic peritoneal dissemination. We examined
      the clinical efficacy of S-1 chemotherapy against gastric cancer with positive
      PLC after macroscopically curative resection. METHODOLOGY: Among our gastric
      cancer patients proving to have positive PLC after operation, 17 treated between
      2000 and 2005 and 20 treated between 1986 and 1999 respectively represented S-1
      and non-S-1 groups, between which we compared survival rates. S-1 was
      administered orally twice daily at a dose of 80 mg/m2/day for 28 consecutive days
      followed by a 14-day pause, thus repeating the cycle every 6 weeks. RESULTS: S-1
      was administered for more than 2 cycles in all patients (median, 10 cycles).
      Grade 3 adverse reactions to S-1 occurred in two patients. Other adverse
      reactions were grade 2 or less. Cumulative survival in the S-1 group was better
      than in the non-S-1 group (p=0.0034), with 1- and 3-year survival rates of 87.5%
      and 71.6% vs. 59.0% and 17.1%. CONCLUSIONS: S-1 is effective as postoperative
      chemotherapy for gastric cancer patients with positive PLC after macroscopically
      curative resection.

PMID- 19102428
TI  - Prospective randomized controlled trial comparing the use of 3.5-mm and 4.8-mm
      staples in gastric surgery.
AB  - BACKGROUND/AIMS: The purpose of this study was to evaluate and compare the use of
      4.8-mm and 3.8-mm staples in gastric resection. METHODOLOGY: A series of 60
      patients underwent distal or proximal gastrectomy. A 4.8-mm GIA universal stapler
      was randomly assigned for use in 50% of the patients and a 3.5-mm GIA universal
      stapler was assigned for use in the remaining 50%. RESULTS: Bleeding was observed
      in 20 patients (12 in the 4.8-mm group and eight in the 3.5-mm group). In the 4.8
      mm group, bleeding was less frequent in patients with a stomach wall thickness of
      7.0-9.0mm. In the 3.5-mm group, bleeding was less frequent in patients with a
      stomach wall thickness of 5.0-7.0mm. Inappropriate staple formation was observed
      in patients with thick stomach walls in each group. CONCLUSIONS: The appropriate
      staple size for gastric surgery may depend on the thickness of the stomach wall.

PMID- 19102429
TI  - A novel surgical technique: gasless laparoscopy-assisted gastrojejunostomy.
AB  - Gastrojejunostomy is often performed to relieve the symptoms of gastric outlet
      obstruction. The recent trend is toward minimally-invasive procedures to reduce
      recovery time and increase quality of life. However, several problems and
      complications have been reported using gas-filled laparoscopy, especially in the
      elderly and patients with poor cardiopulmonary function. Consequently, we
      developed a new gasless laparoscopy-assisted gastrojejunostomy procedure to
      eliminate the cardiopulmonary risks of gas-filled laparoscopic surgery. The
      working cavity is created by lifting the mini-laparotomy incision using a self
      supporting retractor that we designed, and two to three additional working ports
      are created. Antecolic side-to-side gastrojejunostomy is performed using an
      endostapler. Eleven patients (3 males and 8 females) underwent this new procedure
      between April 2005 and May 2006. Their median age was 75 years (range 34 to 85),
      and eight of the eleven had more than three comorbid conditions. The median
      duration of postoperative flatus was 2 days (1-10 days), and the median hospital
      stay 10 days (5-28 days). No postoperative leakage occurred. However, one patient
      with postoperative gastrostasis and another with ileus due to cancer-related
      peritonitis were noted; fortunately, both responded to conservative medical
      management. In conclusion, our gasless, laparoscopy-assisted gastrojejunostomy
      procedure appears to be both safe and effective in patients with gastric outlet
      obstruction.

PMID- 19102430
TI  - [Termination of pregnancy after the 20-week ultrasonographic examination: haste
      and caution].
AB  - The recently introduced ultrasonographic screening programme for the detection of
      fetal structural anomalies at 20 weeks' gestation is leading to a growing number
      of cases with an unclear prognosis. This article presents the decision-making
      process which followed the screening of two women: one aged 36 years, where a
      post-screening work-up was conducted and swiftly led to well-balanced decision
      making to abort a fetus with trisomy 21, and one woman aged 30 years, in whom
      repeated non-decisive results of further diagnostic tests ultimately led to a
      hasty decision to abort the pregnancy. Up to 24 weeks, current Dutch law allows
      the couple to decide to have a termination of pregnancy; thereafter the legal
      possibility of having a termination is very limited. This may lead to rushed
      decision-making. It is argued that careful decisions in these matters are more
      important than staying within the 24-week limit. The national central committee
      ofexperts which is responsible for the evaluation of all abortions after 24 weeks
      gestation in the so-called category 2 cases (conditions which will lead to
      serious and irreparable functional disorders, such as severe spina bifida and
      hydrocephalus, but which are compatible with life) should take account of this
      dilemma ofhaste and caution.

PMID- 19102431
TI  - [Sensible family planning: pitfalls and dilemmas].
AB  - In a recent article in this journal it was stated that Dutch women were sensible
      in having their first child between the ages of 25 and 35 years. One of the
      conclusions was that associated health risks increase after the age of 35 but are
      still acceptable even at the age of 40. We demonstrate that these conclusions
      were based on flawed assumptions. Postponing pregnancy until after the age of 30
      increases the risks of infertility and breast cancer. Motherhood at a later age
      is associated with an increase in obstetrical complications, miscarriage and
      other adverse effects on the child. Therefore, for couples planning a family with
      2 children or more, it would be sensible to have the first pregnancy not long
      after the mother reaches the age of 30 years, or even earlier. Couples should be
      informed on the risks of late parenthood in order to be able to take the right
      decisions concerning family planning.

PMID- 19102432
TI  - [Success of carotid endarterectomy dependent on type of atherosclerotic plaque
      and gender, among others].
AB  - Carotid endarterectomy (CEA) reduces the risk of stroke in both symptomatic and
      asymptomatic patients with a high-grade stenosis of the internal carotid artery.
      Surgery, however, is less beneficial for women than for men. Besides gender,
      other factors, like degree ofstenosis and plaque morphology, influence the risk
      of stroke and the beneficial effect of CEA. A recent study shows that women,
      asymptomatic women in particular, have more stable atherosclerotic carotid
      plaques than men. Increasing knowledge regarding local plaque characteristics
      should be carried through to clinical practice. Further studies, especially
      prospective studies, are needed to identify subgroups of patients that will
      benefit most from CEA. Low surgical morbidity and mortality remain a prerequisite
      to perform CEA in symptomatic carotid stenosis and even more so in asymptomatic
      carotid stenosis.

PMID- 19102433
TI  - [Use of medicines to reduce the risk of postoperative cardiac death: too early
      for guidelines].
AB  - In a review in this journal, Feringa et al. focused on the prevention of
      cardiovascular complications after non-cardiac surgery. Beta-blockers and statins
      appear to be the most effective in reducing post-operative mortality due to
      cardiac events. We have doubts about the external validity of the studies on
      cardiovascular risks after non-cardiac surgery. A major limitation is that
      conclusions for all patients have been drawn from relatively small samples with a
      selection of high-risk patients. Guidelines based upon such studies are
      'premature', possibly dangerous and unethical, since the acceptance of such
      guidelines would preclude large scale studies to confirm the conclusions of the
      small studies so far performed. Perioperative beta-blockade is only needed in a
      subgroup of patients with a high-risk cardiac profile.

PMID- 19102434
TI  - [Perioperative beta-blockade for reduction of cardiovascular complications in non
      cardiac surgery: advantages and disadvantages].
AB  - The results of the recently published PeriOperative ISchemic Evaluation (POISE)
      trial show that perioperative use of metoprolol in patients with atherosclerosis
      undergoing major non-cardiac surgery reduces the risk of cardiovascular
      complications. This effect was primarily produced by a 1.5% reduction in non
      fatal myocardial infarction (MI), but this advantage was outweighed by a 0.8%
      increase in total mortality and a 0.5% increase in nonfatal stroke. These
      results, combined with previous meta-analyses, confirm that non-fatal MI is
      reduced at the cost of a statistically significant increase in stroke rate and a
      near significant increase in mortality. It is likely that the increase in
      complications is due to a high dose of metoprolol being given too shortly before
      the operation. These findings call for judicious perioperative use of adrenergic
      beta-antagonists in cardiac-high-risk patients undergoing high risk non-cardiac
      surgery. Dosage should be lower and administration should be implemented longer
      before the operation.

PMID- 19102435
TI  - [Perioperative risk reduction in vascular surgery via cardio-protective
      medication].
AB  - Cardiovascular complications are the leading cause of death after noncardiac
      surgery. Preoperative identification of patients with underlying coronary artery
      disease is important, and appropriate treatment strategies should be implemented
      in these patients in order to reduce the risk of perioperative complications.
      Based on recent findings, preoperative risk stratification models have been
      developed to identify high-, intermediate- or low-risk patients; the
      concentration of natriuretic peptides is a promising new preoperative risk
      marker. beta-blockers considerably reduce this risk. In clinical practice,
      important factors are adequate beta-blocker dosage, tight perioperative heart
      rate control and continuation of beta-blockers after discharge. Recently, statins
      have emerged as drugs with perioperative cardioprotective properties, but more
      randomized clinical trials are needed before routine administration ofstatins can
      be recommended. Perioperative medical management should focus on improvements not
      only in the short-term but also in the long-term.

PMID- 19102436
TI  - [Prevention of perioperative cardiac complications in non-cardiac surgery: an
      evidence-based guideline].
AB  - Approximately 2.5% of the patients undergoing non-cardiac surgery suffer from
      perioperative cardiac complications. These are associated with a mortality of
      20.60%, a longer stay in hospital and higher costs. The risk factors for
      perioperative cardiac complications are: high-risk surgery, ischaemic heart
      disease, a history of congestive heart failure, cerebrovascular disease,
      diabetes, and renal failure. Recently, the scope of medical management has
      shifted from assessing and treating underlying culprit coronary lesions toward
      coronary plaque stabilisation and prevention of myocardial oxygen supply demand
      mismatch. Currently, the prevention of cardiac problems consists of
      identification of the patients at risk, optimisation of the preoperatieve
      condition by modification of underlying risk factors, optimisation of the
      perioperative medication with adrenergic beta-antagonists, statins, and
      acetylsalicylic acid, adequate perioperative monitoring and measures to prevent
      myocardial ischaemia. These include adequate sedation and analgesia, adequate
      oxygenation, oxygen transport, and ventilation, and if necessary additional
      cardiac medication.

PMID- 19102437
TI  - [Blood pressure control in patients with a symptomatic carotid artery stenosis].
AB  - Carotid artery stenosis is an important cause of transient ischaemic attacks
      (TIAs) and ischaemic strokes, and is associated with a particularly high risk of
      recurrent stroke both in the acute phase and the long-term. Early secondary
      preventive measures would therefore seem warranted. Carotid endarterectomy (CEA)
      is an effectively therapy in patients with a severe symptomatic stenosis.
      Hypertension is an important risk factor for recurrent stroke both in the acute
      phase and the long-term. Moreover, hypertension is an important risk factor for
      complications of CEA. In patients on the waiting list for CEA, following a TIA or
      a non-disabling ischaemic stroke, it would seem worthwhile to attempt to start
      antihypertensive treatment after approximately 24 h, and to at least strive after
      a preoperative systolic blood pressure of < 180 mmHg and a diastolic blood
      pressure of < 90 mmHg. In patients who cannot undergo surgery in the desirable
      short run, hypotensive treatment must be considered in the context of secondary
      prevention. The blood pressure target level depends on the presence or absence of
      a severe unilateral or bilateral stenosis (> 70% lumen diameter). In
      postoperative hypertension one must strive after a blood pressure < 140/90 mmHg,
      thereby avoiding an excessively rapid hypotensive response (> 25% daily).
      Patients with a TIA or an ischaemic stroke and a carotid artery stenosis must
      also be treated with antiplatelet agents and a statin, while other vascular risk
      factors must be controlled.

PMID- 19102438
TI  - [Diagnostic image (398). A man with swollen elbows].
AB  - A 28-year-old male haemodialysis patient presented with bilateral swollen elbows
      due to tumoral calcinosis.

PMID- 19102439
TI  - [Differences between men and women in the composition of atherosclerotic plaque,
      as an explanation for the lower success rate of carotid endarterectomy in women].
AB  - OBJECTIVE: To determine whether men and women differ in the histological
      characteristics of plaque material removed at carotid endarterectomy. DESIGN:
      Observational and descriptive. METHODS: Carotid endarterectomy plaque specimens
      obtained from 45 degrees consecutive patients (135 women, 315 men) were assessed
      for the presence of macrophages, smooth muscle cells, collagen, calcifications,
      and luminal thrombus by means ofimmunohistochemical staining. The plaques were
      categorised in 3 phenotypes according to the overall presentation of histological
      characteristics and the lipid level. Protein was isolated from the plaques to
      determine the interleukin-6 (IL-6) and IL-8 concentrations and the activity of
      matrix metalloproteinase-8 (MMP-8) and MMP-9. RESULTS: Atheromatous plaques (>
      40% fat) were less frequently observed in women than in men (22 versus 40%; p <
      0.001). In addition, more women than men had a low macrophage staining (18 versus
      11%; p = 0.05) and strong smooth muscle cell staining (38 versus 24%; p = 0.001).
      Compared with men, women had a lower plaque concentration of IL-8 and lower MMP-8
      activity. The observed differences were most pronounced in the asymptomatic
      group. An atheromatous plaque occurred in 9% of asymptomatic women compared to
      39% ofasymptomatic men (p = 0.02). Moreover, a large proportion of plaques
      obtained from asymptomatic women showed high smooth muscle cell content (53
      versus 30%; p = 0.03) and high collagen content (55 versus 24%; p = 0.003). All
      relations between gender and plaque characteristics, except for MMP-8, remained
      the same in a multivariate analysis that was adjusted for clinical presentation
      and other cardiovascular risk factors. CONCLUSION: Women with a carotid stenosis
      had more stable plaques than men, independent of clinical presentation and
      cardiovascular risk profile. Asymptomatic women demonstrated the highest
      prevalence of stable plaques. These findings may explain why women benefit less
      from carotid endarterectomy than men.

PMID- 19102440
TI  - [Assessment of late pregnancy terminations, 2004-2007].
AB  - OBJECTIVE: To provide an inventory of the reported late terminations of pregnancy
      because ofa severe anomaly of the unborn child, i.e. termination after 24 weeks
      of pregnancy, in The Netherlands for the period 2004-2007. DESIGN: Inventory and
      descriptive. METHOD: A description is given of the various assessment procedures
      for the termination of pregnancy after 24 weeks. A distinction is made between
      abortion for lethal foetal abnormalities (category 1) and severe functional
      impairments with a limited chance for survival of the unborn (category 2). The
      level of caution exercised in decision making and performing category 1
      terminations is assessed by the professional group, namely by the assessment
      committee for Late Pregnancy Termination of the Dutch Association for Gynaecology
      and Obstetrics. Since 15 March 2007, late pregnancy terminations that fall under
      category 2 have by law been assessed by a national central committee of experts.
      An overview of the reported cases of late terminations of pregnancy in the
      Netherlands for the period 2004-2007 is given. RESULTS AND CONCLUSION: The number
      of reported terminations of pregnancy after 24 weeks (n = 72) has declined
      considerably since the early 1990s. A possible explanation is that due to
      increasing technological improvements and the implementation of prenatal
      screening in early preg-nancy, an abortion can be performed before the 24th week
      of pregnancy if any severe abnormalities are observed.

PMID- 19102441
TI  - [Alpha-foetoprotein assessment in amniotic fluid for the detection of neural tube
      defects: limited added value beyond week 20 ultrasound; retrospective study].

PMID- 19102442
TI  - Doing nothing about ethics.

PMID- 19102443
TI  - Why publish Mew?

PMID- 19102444
TI  - The changes at Delta.

PMID- 19102445
TI  - Antitrust law cannot be ignored by dentists.

PMID- 19102446
TI  - Determine the market value of each position in your office.

PMID- 19102447
TI  - Are published listings of 'top dentists' unethical?

PMID- 19102448
TI  - BCS rates adjust; benefits added.

PMID- 19102449
TI  - Seven ways to prevent burnout.

PMID- 19102450
TI  - Can sugarless lollipops reduce tooth decay?

PMID- 19102451
TI  - Delegating duties the right way.

PMID- 19102452
TI  - Understanding Delta Dental's new payment policies.

PMID- 19102453
TI  - Policies help plans cover more people.

PMID- 19102454
TI  - Ameloblastic fibro-odontoma: case report and review of the literature.

PMID- 19102455
TI  - Psychometric properties of the burden inventory for relatives of persons with
      psychotic disturbances.
AB  - Earlier studies have shown that close relatives are heavily burdened when a
      family member has schizophrenia. The current purpose was twofold: (1) to examine
      the psychometric properties for a test of the burden of family members, one used
      in Swedish clinical practice (the Care Burden Scale for Relatives), and (2)
      develop a shortened version with the same or better psychometric properties. 99
      close relatives, 34 men and 65 women of the same number of patients who had been
      diagnosed with schizophrenia, schizoaffective disorder, or delusional disorder,
      completed the Care Burden Scale for Relatives and a visual analog scale measuring
      perceived global burden on which the total burden was assessed. Patients of the
      close relatives were assessed on clinical tests often used in psychiatric care to
      validate the external criteria, such as severity of symptoms and level of
      functioning. The resulting version, the Burden Inventory for Relatives of persons
      with psychotic disturbances, showed good psychometric properties which simplifies
      data collection from relatives of patients with psychotic disturbances. In this
      study, relatives of those patients not in remission evinced a significantly
      greater family burden.

PMID- 19102456
TI  - Psychometric properties of the Spanish adaptation of the Barratt Impulsiveness
      Scale-11-A for children.
AB  - Given difficulty in having children assess their own behaviour, there are few
      self-reports on child impulsivity. With the exception of Eysenck's 16
      questionnaire, there are no self-report measures of impulsivity in children with
      good psychometric properties. The present study tested the possibility of using
      the adolescent version of the Barratt Impulsiveness Scale-11 with children. For
      this purpose the questionnaire was translated and backtranslated and administered
      to school children (182 boys and 195 girls) ages 8 to 12 years (M = 10.4, SD =
      0.9). The data were analysed by exploratory factor analysis, to evaluate the
      factorial structure of the questionnaire, the fit of the proposed solution, and
      internal consistency reliabilities. Results seem to indicate that this
      questionnaire may be useful in assessing impulsivity in children. The three
      factor structure showed slight differences with the initial questionnaire
      proposed by Barratt and had good or sufficient internal consistency (depending
      upon the scale) across the 8- to 12-yr.-old age range.

PMID- 19102457
TI  - Evaluation of a program for reduction of childhood aggression.
AB  - The Peaceful Alternatives to Tough Situations (PATTS) was evaluated for reduction
      of childhood aggression. A quasi-experimental pre- and posttest comparison group
      design was used to evaluate 71 PATTS participants who were selected by school
      personnel or juvenile caseworkers due to prior aggression. The participants
      responded to the Conflict Tactics Scale-Revised and a modified version of the
      Mauger Forgiveness Scale on the first and last group meetings. Analyses (n=71
      PATTS; n=35 comparison group) indicated significant positive decreases in
      physical assault, psychological aggression, and vengefulness, and increased
      forgiveness of others in the PATTS group participants. There was also a reduction
      of school suspensions, principal referrals, or new criminal offenses for PATTS
      group participants.

PMID- 19102458
TI  - Religion and mythology in a sample of undergraduate psychology of women courses.
AB  - The coverage of religion and mythology in undergraduate courses in the Psychology
      of Women was explored by (a) surveying a sample of undergraduate instructors
      (N=72); and (b) examining coverage in textbooks on the Psychology of Women
      (N=95). 48.6% of teachers said they include some coverage, while 43.1% said they
      never do. The total percentage of coverage in textbooks is small, ranging from a
      mean of 2.0% in the 1970s to 1.1% in the current decade.

PMID- 19102459
TI  - Evening types among german university students score higher on sense of humor
      after controlling for big five personality factors.
AB  - Humor research has focused on relationships between humor and various personality
      traits. As personality and morningness-eveningness, as well as personality and
      humor, are related based on genetics and neurobehavioral function, one might also
      expect a relationship between humor and chronotype. 197 students responded to the
      Composite Scale of Morningness as a measure of chronotype, the Sense of Humor
      Questionnaire and a 10-item version of the Big Five Inventory. Individuals
      scoring as evening types reported a greater sense of humor than morning
      individuals, with higher morningness scores. In a stepwise linear regression,
      Extraversion, Agreeableness, Openness, and Chronotype each accounted for a
      significant amount of variance in sense of Humor scores. That is, the
      relationship between scores on Sense of Humor and evening orientation was
      significant after controlling for personality dimensions. Eveningness was related
      to sense of Humor scores in women but not in men. Social but not cognitive humor
      was predicted by eveningness.

PMID- 19102460
TI  - Love scripts of persons with antisocial personality.
AB  - This study compared the scripts of love among 60 prison inmates diagnosed with
      Antisocial Personality Disorder and those of 40 inmates without an Antisocial
      Personality Disorder diagnosis but low antisocial tendencies, and a control group
      of 100 adult students in extramural or evening secondary schools without
      Antisocial Personality Disorder traits. The study focused on emotional knowledge
      about love of the group with Antisocial Personality Disorder, as they present
      lack of capacity for love. The study was done to examine how they perceive love
      and how much knowledge they have about love. All described their reactions to a
      photograph of a couple hugging each other. The content of these scripts, analyzed
      in terms of description of actors, their actions and emotions, and length of
      description, was compared among the groups. The scripts of love by antisocial
      inmates contained more actors' feelings and strong emotions, as well as more
      descriptions of actors' traits, their actions, and presumptions. The inmates with
      Antisocial Personality Disorder showed more focus on themselves when they
      described love than the other inmates and the controls.

PMID- 19102461
TI  - Dreams by persons with mood disorders.
AB  - This work evaluated the structure of dreams in depressed patients. The verbal
      reports of dreams of 100 depressed patients were compared with 251 dreams of a
      control group. In accordance with the Jungian thought, which views dreams as
      texts, dream reports were assessed using textual analysis processing techniques.
      Significant differences were found in parameter values, as well as in the role of
      the dreamer as an external observer. Considering the length of the dreams' texts,
      depressed patients used fewer words than the control group. With regard to
      sensory field, there were fewer lemmas referring to sight for depressed patients
      than for healthy participants. This work seems to confirm the value of textual
      analysis in the study of oneiric material

PMID- 19102462
TI  - The Japanese version of the Coping Orientation to Problems Experienced: a study
      of Japanese schoolteachers.
AB  - To investigate the internal consistency reliability and three types of validity
      of the Coping Orientation to Problems Experienced (COPE), a survey was conducted
      among 209 English schoolteachers in Japan. The Japanese version of the COPE
      Inventory was developed through a back-translation process. Cronbach coefficients
      alpha for the Japanese version were above .70 for all subscales except five,
      including Acceptance and Restraint, so internal consistencies for these five were
      insufficient. Goodness of fit indexes for a confirmatory factor analysis were
      acceptable except for the Comparative Fit Index. Scores on COPE subscales were
      significantly correlated with scores on other tests (29 of 75 correlations were
      in the expected directions). Further exploration is required for several
      subscales and for generalization to Japanese-speaking populations in careers
      other than teaching to ensure the Japanese version of the COPE will be useful in
      assessing coping strategies. Given the limitations, present data for Japanese
      teachers are encouraging.

PMID- 19102463
TI  - Using the knowledge-and-appraisal personality architecture to predict self
      efficacy within individual persons.
AB  - The knowledge-and-appraisal personality architecture has potential as a
      theoretical framework for understanding the formation of self-efficacy in
      individuals. Two patterns were observed within 14 of 17 individual persons: a
      pattern of strong self-efficacy was displayed across outdoor recreation
      activities for which a self-descriptive attribute was viewed as an asset to
      successful performances, and a pattern of relatively weak self-efficacy was
      observed across outdoor recreation activities for which the same attribute was
      considered a hindrance to performances. Although the theory predicts self
      efficacy within individuals, more research is needed to assess why the theory is
      not accurate in all cases.

PMID- 19102464
TI  - Hope as a predictor of academic performance.
AB  - This study was designed to assess whether the two subscales of the Hope Scale
      significantly predict semester grade point average (GPA), over and above American
      College Test (ACT) scores and Trait Anxiety (Spielberger State-Trait Anxiety
      Inventory.) The Hope Scale includes two subscales, goal-directed determinism
      (Agency) and the ability to plan ways to attain goals (Pathway). As predicated,
      scores on the Hope Scale correlated significantly with semester GPA. Scores on
      the Agency subscale correlated positively with semester GPA in this college
      sample, but not those on the Pathways subscale. Partial correlations retained the
      association of scores on the Agency subscale and GPA, even when intelligence (ACT
      scores) and anxiety (Trait Anxiety scores) were controlled. Implications are
      discussed.

PMID- 19102465
TI  - Development of a Korean version of a core self-evaluations scale.
AB  - The present study tested a scale which measures core self-evaluation and was
      applied to two samples of Korean military members (Sample 1 N=181; Sample 2
      N=280). Analysis indicated that seven items of the original 12-item scale
      developed by Judge, Erez, Bono, and Thoresen loaded on one factor and were
      internally consistent. Moreover, scores were correlated, as expected, with the
      four core traits which have been used as indirect measures of core self
      evaluations (viz., self-esteem, generalized self-efficacy, neuroticism, and locus
      of control), as well as affect and job satisfaction. In sum, results suggest that
      core self-evaluation can be measured validly in an Eastern culture, and the
      results should serve as a basis for extending this research in an international
      setting.

PMID- 19102466
TI  - Faculty perceptions of undergraduate students' participation in regional
      psychology conferences.
AB  - Faculty responded to a survey regarding submission guidelines and decision-making
      processes to regional psychology conferences for undergraduate students.
      Respondents' mean age was 52.2 yr. (SD = 10.8), mean years of teaching experience
      was 22.5 (SD = 10.7), and 49.7% were women. Analyses indicated that students
      should know submission guidelines and evaluative criteria prior to submission,
      but may not. Results are presented to provide feedback for faculty about the
      conference submission process.

PMID- 19102467
TI  - The crux of the method: assumptions in ordinary least squares and logistic
      regression.
AB  - Logistic regression has increasingly become the tool of choice when analyzing
      data with a binary dependent variable. While resources relating to the technique
      are widely available, clear discussions of why logistic regression should be used
      in place of ordinary least squares regression are difficult to find. The current
      paper compares and contrasts the assumptions of ordinary least squares with those
      of logistic regression and explains why logistic regression's looser assumptions
      make it adept at handling violations of the more important assumptions in
      ordinary least squares.

PMID- 19102468
TI  - The personality dispositional approach to job satisfaction and organizational
      commitment.
AB  - The extent to which personality traits as defined by the Big Five model account
      for the unique variance in job satisfaction and organizational commitment was
      studied. Analyses of data obtained from 96 employees of two public institutions
      showed that 58 and 44% of the explained variance in job satisfaction and
      organizational commitment, respectively, were accounted for by factors in this
      personological framework.

PMID- 19102469
TI  - Therapist stress, coping, career sustaining behavior and the working alliance.
AB  - Relations were examined among therapist stress, coping styles, career sustaining
      behaviors and therapist working alliance. 160 therapists completed a demographic
      questionnaire, a rating of stress experienced in work as a psychotherapist, a
      rating of stress experienced in work with an individual client, the Perceived
      Stress Scale, the Career Sustaining Behavior Questionnaire, the COPE, and the
      Working Alliance Inventory. After controlling for demographic and therapists'
      stress variables, and alternating entry of Career Sustaining Behavior and COPE
      scores in the regression model, Career Sustaining Behavior contributed
      significant variance to predicting working alliance, and COPE scores accounted
      for significant variance in working alliance with active coping a significant
      predictor. Career Sustaining Behavior and COPE scores entered together accounted
      for significant unique variance in Working Alliance with career sustaining
      behavior and avoidant coping identified as significant predictors.

PMID- 19102470
TI  - Salivary alpha amylase levels under conditions of extreme examination stress.
AB  - 11 healthy adult graduate students were studied on two separate occasions 2 wk.
      apart at the same time of day. Self-rating of perceived stress and serial
      measurements of salivary alpha-amylase levels were performed at T1 = 15 min.
      before, T2 = 1 min. before, T3 = 1 min. after, and T4 = 15 min. after an event.
      The events were a highly stressful master's degree oral examination on the first
      occasion and 15 min. of typing on a computer on the second occasion as a control
      activity. A kinetic assay was used to estimate salivary alpha-amylase activity.
      Students rated higher stress on the oral examination day, and their salivary
      alpha-amylase activity was higher during the oral examination period than on the
      second less stressful control day.

PMID- 19102471
TI  - Childhood abuse related to nicotine, illicit and prescription drug use by women:
      pilot study.
AB  - A sample of 811 women ages 18 to 59 (M=26.0, SD=6.5) responded to an
      advertisement by telephone. Inquiries were made about childhood abuse status and
      adult use of alcohol, nicotine, and prescription and illicit drugs. Significant
      associations were noted for reported sexual, physical, and emotional childhood
      abuse with use of nicotine, marijuana, and antidepressants in adulthood. Reported
      childhood physical and emotional abuses were also significantly associated with
      use of cocaine and anxiolytics, and sexual abuse with antipsychotic use in
      adulthood. Only childhood emotional abuse was associated with the use of sleeping
      pills. Number of types of abuse was significantly related with use of nicotine,
      marijuana, cocaine, antidepressants, antipsychotics, and anxiolytics. Alcohol use
      was not related to any type of abuse. The long-term effects of childhood
      emotional abuse may be just as severe as physical or sexual abuse.

PMID- 19102472
TI  - Resampling permutation probability values for weighted kappa.
AB  - A permutation algorithm and associated FORTRAN program are provided for
      resampling weighted kappa. Program RWK provides the weighted kappa test statistic
      and the resampling one-sided upper-tail probability value.

PMID- 19102473
TI  - Implicit theory of athletic ability and self-handicapping in college students.
AB  - Self-handicapping is a maladaptive behavior which undermines students'
      achievements, but the antecedents of self-handicapping are not well studied in
      physical education. The aim was to examine the relations of implicit theory of
      abilities and self-handicapping in physical education. 264 college students,
      whose mean age was 20.3 yr. (SD = 1.7), completed the Conceptions of the Nature
      of Athletic Ability Questionnaire-2 and Self-handicapping Scale for Sport.
      Analysis indicated entity beliefs positively predicted reduced effort and making
      excuses. Also, incremental beliefs negatively predicted reduced effort. Results
      are discussed in terms of implicit theory of ability and self-handicapping.
      Directions for research and implications are stated.

PMID- 19102474
TI  - A meta-analysis examining the relations among pathological gambling, obsessive
      compulsive disorder, and obsessive-compulsive traits.
AB  - Pathological gambling has been proposed to belong to the obsessive-compulsive
      spectrum of disorders. Disorders on this spectrum are thought to share similar
      clinical features, neurobiology, and responses to treatment as Obsessive
      Compulsive Disorder. A total of 18 studies were included in a meta-analysis to
      assess the strength of the association between these disorders. A strong
      relationship (effect size = 1.01) was found between pathological gambling and
      obsessive-compulsive traits. A weak relationship was found between pathological
      gambling and Obsessive-Compulsive Disorder (.07) and Obsessive-Compulsive
      Personality Disorder (effect size = .23). These results suggest pathological
      gambling and Obsessive-Compulsive Disorder are distinct disorders. However,
      pathological gamblers do appear to show high rates of obsessive-compulsive traits
      relative to controls. These findings are only moderately supportive of the
      inclusion of pathological gambling within the obsessive-compulsive spectrum of
      conditions.

PMID- 19102475
TI  - Random assignment of intervention points in two-phase single-case designs: data
      division-specific distributions.
AB  - The present study explored the statistical properties of a randomization test
      based on the random assignment of the intervention point in a two-phase (AB)
      single-case design. The focus is on randomization distributions constructed with
      the values of the test statistic for all possible random assignments and used to
      obtain p values. The shape of those distributions is investigated for each
      specific data division defined by the moment in which the intervention is
      introduced. Another aim of the study consisted in testing the detection of
      inexistent effects (i.e., production of false alarms) in autocorrelated data
      series, in which the assumption of exchangeability between observations may be
      untenable. In this way, it was possible to compare nominal and empirical Type I
      error rates to obtain evidence on the statistical validity of the randomization
      test for each individual data division. The results suggest that, when either of
      the two phases has considerably fewer measurement times, Type I errors may be too
      probable and, hence, the decision-making process to be carried out by applied
      researchers may be jeopardized.

PMID- 19102476
TI  - Justice, leader-member exchange, and job performance: are their relationships
      mediated by organizational culture?
AB  - The hypothesis that organizational justice is linked to leader-member exchange,
      which in turn affects job performance, was examined. It was predicted that two
      dimensions of organizational culture, employee supportiveness and attention to
      detail, would affect both leader-member exchange and organizational justice.
      Results from a sample of 75 employees of a public service organization found
      solid support for the predicted model. Contrary to expectations, however, the two
      aspects of organizational culture were found to play a mediating role: they were
      affected by organizational justice and in turn affected leader-member exchange.
      The theoretical implications of the results are discussed.

PMID- 19102477
TI  - Differences between genuine and simulated suicide notes.
AB  - A text analysis of 33 pairs of genuine and simulated suicides indicated that
      simulated notes are less concerned with others, focus more on the reasons for
      their suicide, and use more negations (such as no and not).

PMID- 19102478
TI  - Foot-in-the-door technique using a courtship request: a field experiment.
AB  - "Foot-in-the-door" is a well-known compliance technique which increases
      compliance to a request. Many investigations with this paradigm have generally
      used prosocial requests to test its effect. Evaluation of the effect of foot-in
      the-door was carried out with a courtship request. 360 young women were solicited
      in the street to accept having a drink with a young male confederate. In the foot
      in-the-door condition, before being solicited to have a drink, the young woman
      was asked to give directions to the confederate or to give him a light for his
      cigarette. Analysis showed foot-in-the-door was associated with greater
      compliance to the second request. The theoretical implication of such results
      with this nonprosocial request are discussed.

PMID- 19102479
TI  - Spouse selection: important criteria and age preferences of an Iranian sample.
AB  - Importance of different criteria and age preference in spouse selection for
      single and married young Iranian adults was examined. The sample included 104
      married (49 male, 55 female) and 112 single (51 male, 61 female) students. A 26
      item scale developed for this study included 4 items related to demographic
      factors, 3 items on preferences for the ideal age of marriage, and 19 Likert-type
      items asking about criteria important for spouse selection. Analysis indicated
      that, in Iran, commitment, chastity, refinement, and health are four important
      criteria for spouse selection among male and female and single and married
      persons. Also, experience of marriage for married males may increase maturity,
      social prestige, family background, having a job, and age as criteria for
      choosing a spouse. On the other hand, marriage experience for females may
      decrease the importance of social skills, housekeeping, and autonomy for
      selecting a spouse.

PMID- 19102480
TI  - On the integrity of reliability estimation in classical test theory: the case for
      an additive coefficient of stability.
AB  - This article addresses deficiencies in the most widely used estimators of
      reliability and draws attention to the reason that this issue is important.
      Accurate calibration of relationships between constructs is critical to theory
      development. Unless workers have accurate estimates of scale reliability,
      accurate estimates of those relationships will not be forthcoming because the
      classical disattenuation formula requires them. This article shows that classical
      test theory can easily accommodate the delineation of its error component E in
      test scores into two sources, inconsistency across content (E1) and inconsistency
      across time (E2). Viewed from this extended model, the alternate forms approach
      to reliability estimation is complete in that it gauges simultaneously both
      sources of error. Because that approach is rarely used today for that purpose,
      the integrity of estimation has been lost. In its place arose estimators of
      partial reliability--those for estimating generalizability over one medium or the
      other, but not both, thereby precluding the additivity of error components.
      Recent developments promise to restore the integrity of the alternate forms
      approach without the need for alternate forms and suggest an additive alternative
      to the current nonadditive coefficient of stability.

PMID- 19102481
TI  - Acculturation, optimism, and relatively fewer depression symptoms among Mexican
      immigrants and Mexican Americans.
AB  - The mental health of individuals of Mexican origin may vary as a function of
      native status (i.e., Mexican born or U.S.A. born). Some have reported that
      Mexican Americans tend to display more depressive symptoms than Mexican
      immigrants. The present goal was to estimate the associations among acculturation
      and native status, and explore relative deprivation in the prevalence of
      depression. Participants included 153 individuals of Mexican origin who completed
      the Acculturation Rating Scale for Mexican Americans, the Beck Depression
      Inventory-II, the Revised Generalized Expectancy for Success Scale, and relative
      deprivation questions. Analyses indicated women and those scoring low on
      acculturation were significantly more likely to report depressive symptoms.
      Participants who felt they had relatively better family happiness than Euro
      Americans reported lower depressive symptoms. So participants' sex,
      acculturation, and relative lack of depressive symptoms allow better
      understanding of depressive symptoms among these Mexican Americans and Mexican
      immigrants.

PMID- 19102482
TI  - Effect of desire to have a baby on risk acceptance in Turkish infertile women.
AB  - The aim of this study was to assess whether the desire to escape the
      psychological condition created by infertility (to have a baby) affected risk
      taking behavior, with the possible relationship between ovarian cancer and
      infertility as the "accepted risk" to overcome infertility. 229 infertile and 204
      fertile women who were patients at the Gulhane Military Medical Academy were
      administered a semistructured questionnaire. Increased ovarian cancer risk was
      accepted by 67.2% of the infertile women in order to have baby. There was no
      significant relation between the woman's age, duration of infertility, knowledge
      of the preventability and curability of ovarian cancer, or acceptable risk. These
      results indicate the importance to Turkish women of overcoming infertility.

PMID- 19102483
TI  - Relationships between Myers-Briggs type indicator measure of psychological type
      and neo measure of big five personality factors in Polish University students: a
      preliminary cross-cultural comparison.
AB  - English-language versions of the Myers-Briggs Type Indicator (Form G) measure of
      psychological type and the NEO-FFI measure of the Big Five personality factors
      were completed by 57 Polish university students fluent in the English language.
      The pattern of correlations between MBTI and NEO-FFI scales for the Polish sample
      was compared to the pattern of correlations for measures of these same constructs
      reported for Americans. Four of the five significant relationships between MBTI
      and NEO-FFI scales reported in the American sample were also recorded in the
      Polish sample: MBTI Extraversion-Introversion with NEO Extraversion, MBTI Sensing
      Intuition and MBTI Judging-Perceiving with NEO-Openness, and MBTI Judging
      Perceiving with NEO Conscientiousness. Pending replication with a larger, more
      representative sample, this preliminary study supports the validity of
      psychological type in Polish society.

PMID- 19102484
TI  - Confidence in judgments of comparative, own, and average person's risk.
AB  - Unrealistic optimism is often assessed using a single question asking people to
      estimate their own risk compared to that of the average person like them.
      However, it has been proposed that such estimates of comparative risk are based
      mainly just on estimates of own risk. In two studies (n=80 and n=65), students
      gave estimates of comparative, own, and average person's risk and rated their
      confidence in these estimates. Confidence was lower for estimates of average
      person's risk than for estimates of own and comparative risk, which were given
      with equal confidence. Results were in accord with the proposal that judgments of
      comparative risk derive principally from judgments of own risk.

PMID- 19102485
TI  - Reasons French drivers gave for committing or refusing to commit to complying
      with speed limits at rehabilitation training courses for traffic-regulation
      offenders.
AB  - A mixed foot-in-the-door procedure was set up to lead offenders participating in
      French driver-rehabilitation training courses to commit to complying with speed
      limits. To improve this procedure, the reasons that led participants in such
      courses to commit or not were investigated in this preliminary study of the road
      safety research programs. The study participants were 89 men (M=34 yr., range =
      18-64 yr., SD=13) attending driver-rehabilitation courses. Among them, 55%
      committed. The commitment was mainly explained by the drivers' will to change
      their speeding behaviour and their refusal by the perceived positive consequences
      of speeding. Moreover, some participants stated that they would be unable to
      follow through with the commitment to comply strictly with speed limits. After
      talking to the participants, it became clear that complying with speed limits was
      understood in a more or less strict way. In subsequent studies, some of the
      reasons given were used to prompt group discussion before asking participants to
      commit, and the meaning of "compliance with speed limits" was better defined.

PMID- 19102486
TI  - Evidence for validity of the revised Levinson and Sanford Anti-Semitism scale.
AB  - Jones-Wiley, Restori, Lee, and Ho (2007) updated and re-estimated the reliability
      and construct validity of the 1944 Levinson and Sanford Anti-Semitism Scale.
      Criterion validity was not adequately supported, given the small number of Jewish
      and Muslim participants. Two separate studies were conducted, (1) a comparison of
      Jewish, Muslim, and Christian religious groups on the Anti-Semitism score and (2)
      the correlation of political preference with the Anti-Semitism scores of college
      students and local community members. These two studies provide evidence
      supportive of the criterion validity of the revised scale.

PMID- 19102487
TI  - Comparison of features of social problem-solving scripts across three groups:
      educable intellectually disabled, socially poorly adapted, and socially well
      adapted students.
AB  - The aim of this research was to compare the features of social problem-solving
      scripts across groups of students with different social problem-solving
      abilities, based on dynamic memory theory. 54 (32 girls/22 boys) educable
      intellectually disabled students, 58 (32 girls/26 boys) socially poorly adapted
      students, and 50 (28 girls/22 boys) socially well-adapted students participated.
      The average ages for educable intellectually disabled, poorly adapted, and well
      adapted students were 13.9 yr. (SD = 1.7), 11.1 yr. (SD = .6), and 11 yr. (SD =
      .4), respectively. A semi-structured interview was designed. 14 social problems
      were proposed to each student. Results showed that the general features of the
      intermediate level of knowledge structure based on a hierarchical model of script
      theory are helpful in describing the differences among the groups regarding their
      "social problem-solving script". In general, findings indicated that educable
      intellectually disabled students (segregated from the mainstream in Iran),
      compared to the other two groups of students, are less mature in their emotions,
      use ineffective self-regulation strategies, and have goals that are not
      constructive. Some educational recommendations are offered.

PMID- 19102488
TI  - Diary keeping and well-being.
AB  - In a pilot study, 177 female students completed a diary-keeping survey and
      measures of well-being. Diary keepers reported lower well-being than non-diary
      keepers.

PMID- 19102489
TI  - Predicting driving anger from trait aggression and self-control.
AB  - Undergraduates (N=115) completed the Propensity for Angry Driving Scale, Driving
      Anger Scale, and measures of trait aggression and self-control. Aggression and
      self-control correlated significantly with scores on the two scales, and
      Aggression subscale scores explained significant unique variance in both, but the
      predicated interaction of aggression and self-control was not significant. The
      Propensity for Angry Driving Scale is recommended to measure self-reported
      aggressive driving, and the Driving Anger Scale for assessment of driving-related
      anger.

PMID- 19102490
TI  - Effects of past transgressions in an induced hypocrisy paradigm.
AB  - Hypocrisy can be considered as a dissonance state expressed as a combination of
      two factors: commitment (advocating a pronormative position) and mindfulness
      (being aware of past transgressions). Such inconsistency between what people
      advocate and their past behaviors is usually reduced by modifying behaviors or
      behavioral intentions in line with normative advocacy. The aim of this study is
      to examine the conditions under which this set of behaviors (apparent hypocrisy)
      can occur. Specifically, the salience of the transgressions was manipulated:
      participants were led to recall 1 or 4 transgressions varying in severity
      (serious vs harmless). As expected, recalling 4 transgressions led to greater
      behavioral change than recalling only 1 transgression. Surprisingly, recalling 4
      harmless transgressions induced greater behavioral change than recalling 4
      serious transgressions.

PMID- 19102491
TI  - Adults' understanding of child development.
AB  - 230 adults estimated the ages at which children and adolescents ages 1 to 16
      years could perform certain tasks like, "Say the months of the year backwards"
      and "Ride a bicycle". Nearly two-thirds of the participants consistently
      underestimated the age at which young people could perform. A total "correct"
      score, computed for each participant, formed a normal distribution. This score
      was used as a criterion measure for a series of multiple regressions. The
      strongest predictor was the extent to which people had regular contact with
      children, indicating the role of experience.

PMID- 19102492
TI  - Possible relations between general population suicide rates and societal crime: a
      cross-national study.
AB  - Crime may be associated with a less structured society, less social integration,
      and feelings of less security and greater distress among citizens, which
      characteristics may lead to mental illness and subsequent suicide. Therefore, a
      cross-national analysis examining the association of general population suicide
      rates with percent of males and females in the population victimised by different
      categories of crime was undertaken using cross-national data from the World
      Health Organization and United Nations for 42 countries. Spearman correlations
      were generally weak and not statistically significant. Those values were at
      variance with the study's hypothesis and may be explained by several factors,
      including methodological issues. Individual-level case-control or cohort studies
      of suicides and attempted suicides in the general population may permit
      exploration of the relation of general population suicides with experience and
      percent by nations of being victimised by crime.

PMID- 19102493
TI  - [Diagnosis of non-sexually transmitted diseases in genitalia].
AB  - Highly transient population, multiple sexual partners and high prevalence of
      unprotected sex behaviors suggest a potential rapid spread of sexually
      transmitted diseases (STD) in China. However, there are some 200 non-sexually
      transmitted diseases involving the genitalia, etiologically falling into 23
      types. To avoid unnecessary medical disputes, enough attention should be paid to
      the differential diagnosis of non-sexually transmitted diseases in the genitalia.

PMID- 19102494
TI  - [Joint action of phoxim and fenvalerate on spermatogenesis of male rats].
AB  - OBJECTIVE: To assess the joint toxicity of phoxim (Pho) and fenvalerate (Fen) on
      the spermatogenesis of male rats and to clarify its mechanism. METHODS: Based on
      the three administrative levels of factorial analysis (3 x 3) of Pho and Fen, i.
      e. their half lethal dose (LD50) 1/250 LD50 (5.9, 2.4 mg/kg) and 1/50 LD50 (29.4,
      12.0 mg/kg) and the control, 135 adult male SD rats were randomly assigned to9
      groups, the control (0.0 mg/kg), Pho (5.9, 29.4 mg/kg), Fen (2.4, 12.0 mg/kg),
      Pho + Fen (5.9 + 2.4, 5.9 + 12.0, 29.4 + 2.4, 29.4 + 12.0 mg/kg), and treated
      intragastrically with different doses of Pho, Fen and Pho + Fen for 15 and 30
      days. The levels of serum follicle stimulating hormone (FSH), luteinizing hormone
      (LH), testosterone (T) and testis homogenate T were determined by
      radioimmunoassay (RIA), the activity of testicular marker enzymes such as acid
      phosphatases (ACP) and gamma-glutamyl transpeptidase (gamma-GT) examined, and the
      sperm head count measured for the changes of daily sperm production (Spr).
      RESULTS: At 15 days, obvious interaction was observed between Pho and Fen in both
      serum LH and FSH (P < 0.05), as well as between their reproductive toxicities.
      With the increase in doses, the joint action was synergistic in LH (P < 0.05) and
      antagonistic in FSH (P < 0.01) at a high dose ( 29.4 + 12.0 mg/kg). At 30 days,
      marked interaction between Pho and Fen was noted in the content of homogenate T
      (P < 0.05) , with a joint synergistic effect. At 15 and 30 days, with the
      increase of doses, both Pho and Fen reduced Spr and the activity of ACP and gamma
      GT, but Pho + Fen showed no obvious interaction in them (P > 0.05) , and their
      joint action was an additive effect. CONCLUSION: Pho and Fen jointly impaired
      spermatogenesis in a dose- and time-dependent manner. Their joint action
      exhibited mainly as a synergistic effect, an additive effect and increased
      toxicity.

PMID- 19102495
TI  - [Suprapubic puncture: preferable to transurethral catheterization for pressure
      flow determination in BPH patients].
AB  - OBJECTIVE: To compare suprapubic puncture and transurethral catheterization for
      pressure-flow determination during voiding in BPH patients. METHODS: Both
      suprapubic puncture and transurethral catheterization were used for pressure-flow
      determinations during voiding in 23 BPH patients at the mean age of 69.3 years
      (range 57-77 years) and the related parameters were compared by t-test. RESULTS:
      Compared with transurethral catheterization, suprapubic puncture increased Qmax
      by 1.19 mn/s (P <0.05) and MMC by 66.61 ml (P <0.01) , and reduced the pressure
      of detrusor at Qmax (Pdet, Qmax) by 10.57 cmH2O (P < 0.05), URA by 11.39 cmH2O (P
      < 0.01) and AG by 12.94 (P < 0.01). Either according to the Schafer diagram or
      with AG > 40 as the diagnostic standard, there were 16 (69.6%) cases of bladder
      outlet obstruction (BOO) in the suprapubic puncture group and 20 (87.0%) in the
      transurethral catheterization group. CONCLUSION: In pressure-flow determination
      during voiding, suprapubic puncture and transurethral catheterization each have
      its own advantages and disadvantages, but the former is preferred for BPH
      patients. As for other patients, it all depends on specific conditions.

PMID- 19102496
TI  - [Long-term culture and identification of spermatogonial stem cells from BALB/c
      mice in vitro].
AB  - OBJECTIVE: To establish a long-term culture system for mouse spermatogonial stem
      cells (SSCs) and to discuss the key factor that supports mouse SSC self-renewal
      and proliferation. METHODS: Testis cells from 4-6 days postpartum male transgenic
      BALB/c mce were collected by a modified two-step enzymatic digestion method and
      plated on 0. 2% elatin-coated tissue culture plates. The germ cells were enriched
      by differential adherence selections after respectively incubated for 1, 5 and 24
      h and then plated on the mitomycin C-inactivated mouse embryonic fibroblast (MEF)
      feeder layer. The basal culture medium was StemPro-34 SFM supplemented with other
      15 nutrient factors. The 20 ng/ml Glial cell line-derived neurotrophic factor
      (GDNF), 10 ng/ml basic fibroblast growth factor (bFGF) and 200 ng/ml GDNF-family
      receptor alpha 1 (GFRalpha1) were added to the serum-free medium to promote SSC
      proliferation. Several important surface markers and special genes were examined
      by immunocytochemical staining and RT-PCR analysis. RESULTS: After 3-4 days
      culture on the MEF feeder, SSCs proliferated continuously and formed typical
      colonies. SSCs from the BALB/c mice could be cultured in a steady state for 3
      months. Immunocytochemical staining showed that Oct4 was specifically expressed
      in the cultured SSC nucleus and GFRalpha1 strongly expressed on the surface of
      the membrane. RT-PCR confirmed that the cultured SSCs expressed Oct-4, GFRalpha1,
      Sox2 and several other special genes resembling undifferentiated spermatogonia.
      CONCLUSION: SSCs from BALB/c mice could be cultured in the improved culture
      system for 3 months. This culture system could help further understand the
      regulating mechanism of SSCs and might provide an opportunity for the treatment
      of male infertility by SSC transplantation.

PMID- 19102497
TI  - [Aberrant expression of sperm protein 17 enhances migration of ovarian cancer
      cell line HO-8910].
AB  - OBJECTIVE: To explore the effects of aberrant expression of sperm protein 17
      (Sp17) on the migration of the ovarian cancer cell line HO-8910. METHODS: The
      recombinant plasmid pEGFP-Sp17 containing Sp17 and enhanced green fluorescent
      protein gene was transfected into the human ovarian cancer cell line HO-8910 with
      Lipofectamine 2000. The expression of Sp17 was examined by RT-PCR and Western
      blot, and the cell migratory capability detected by Transwell chamber assays.
      RESULTS: Sp17 was expressed as a fusion protein with EGFP after transfected.
      There was a significant difference in the migratory cell number of the
      transfected and the control cells (156.6 +/- 14.9/HP vs 39.3 +/- 8.53/HP, P <
      0.05). CONCLUSION: The aberrant expression of Sp17 greatly enhances the migration
      of ovarian cancer cells.

PMID- 19102498
TI  - [Expression of VEGF in prostate cancer and its correlation with ET-1].
AB  - OBJECTIVE: To investigate the expressions of VEGF in prostate cancer (PCa) and
      benign prostatic hyperplasia (BPH), their clinical significance and their
      relationship with that of ET-1. METHODS: A total of 44 specimens of PCa and 36 of
      BPH tissues were examined by the immunohistochemical Elivision plus method for
      the expressions of VEGF and ET-1. The intensity of staining for VEGF and ET-1 was
      assessed by light microscopy on a scale from "-" to "+ + +". RESULTS: The rates
      of positive expression of VEGF were 69.4% in BPH and 80.9% in PCa, positive
      staining mostly in the cytoplasm of glandular epithelia and cancer cells, and
      strongly positive in all the stroma vascular endothelial cells. The staining
      intensity of VEGF was significantly higher in the PCa than in the BPH group (P <
      0.05) , in the bone metastasis (BM) than in the non-BM group (P < 0.01), and in
      the lowly than in the highly and moderately differentiated PCa tissues (P <
      0.01). The expression of VEGF was positively correlated with that of ET-1 ( r(s)
      = 0.780, P < 0.01). CONCLUSION: VEGF is involved in the development, progression
      and metastasis of PCa. VEGF and ET-1 may play a joint role in its development and
      progression.

PMID- 19102499
TI  - [Vector-mediated shRNA inhibits HIF-1alpha expression in prostate cancer cells].
AB  - OBJECTIVE: To construct a short hairpin RNA (shRNA) vector of the hypoxia
      inducible factor-1alpha (HIF-1alpha), determine its inhibitory effect on the
      expression of the HIF-1alpha gene in PC-3M cells, and investigate its application
      prospects in the treatment of prostate cancer. METHODS: We designed and
      synthesized the shRNA template sequence specific against HIF-lalpha, inserted it
      into the vector psilencer 2.1-U6 to generate the plasmid psilencer-HIF,
      transfected the recombinant plasmid into prostate cancer cell line PC-3M cells
      and detected the transfection efficiency by cotransfection with the pEGFP vector
      as well as the expression of HIF-1alpha by RT-PCR and Western blot. RESULTS: The
      DNA sequencing analysis showed a complete consistency of the recombinant plasmid
      psilencer-HIF with the design. Twenty-four hours after the transfection, the rate
      of transfected plasmid was about (89.26 +/- 4.72)% and the vector-mediated shRNA
      induced RNA interference (RNAi), while 48 hours transfection reduced the HIF
      1alpha mRNA and protein levels by 82.09% and 81.61% respectively (P < 0.01) in PC
      3M cells. CONCLUSION: The shRNA vector was successfully constructed, which can
      effectively suppress the expression of HIF-1alpha in prostate cancer cells.

PMID- 19102500
TI  - [Observation of spermatogenic cells for infertile patients with Y-chromosomal
      microdeletion].
AB  - OBJECTIVE: To assess the spermatogenic function of the infertile patients with Y
      chromosomal microdeletion. METHODS: Thirty-five 23-44 years old patients with
      microdeletions of Y chromosome were included in this study. Three semen analyses
      confirmed that 26 cases were non-obstructive azoospermia and 9 oligospermia with
      sperm count < 1 x 10(6)/ml. They were divided into 3 groups by the locus of
      deletion, 5 cases of AZFa + b + c deletion in group 1, 4 cases of AZFb + c and 3
      cases of AZFb deletion in group 2, and 23 cases of AZFc deletion in group 3.
      Semen was collected and centrifuged, the supernatant removed and the centrifugate
      applied on the clean slides after dilution. Following Wright's-Giemsa staining,
      the slides were viewed under the microscope. Testis histopathological biopsy was
      performed for 6 of the cases. RESULTS: In group 1, no spermatogenic cells were
      observed but only Sertoli cells in 1 case, with a consistency between the result
      of spermatogenic cell test and that of testis biopsy. In group 2, spermatogenic
      cell tests revealed spermatocytes in 6 cases, 2 were proved by testis biopsy with
      sperm maturation arrest in the primary spermatocyte stage, and spermatogenic
      cells of all developmental stages were seen in 1 AZFb deletion patient with the
      same sperm maturation arrest as the above two. In group 3, only primary
      spermatocytes were detected by spermatogenic cell test in 5 oligospermia patients
      but no spermatogenic cells in the 15 azoospermia cases, and biopsy revealed 2
      cases of Sertoli cell-only syndrome. CONCLUSION: The spermatogenic cell test can
      effectively assess the spermatogenic function of AZF deletion patients. Non
      invasive and easily accepted by patients, it is highly recommendable for the
      evaluation of spermatogenesis of patients with Y-chromosomal microdeletion.

PMID- 19102501
TI  - [Primary peripheral T-cell lymphoma of the penis: a case report and review of the
      literature].
AB  - OBJECTIVE: To report a case of primary peripheral T-cell lymphoma of the penis.
      METHODS: We analyzed the clinicopathological characteristics of the case of
      primary peripheral T-cell lymphoma using histological, cytochemical and
      immunohistochemical methods and by review of the literature. RESULTS: The patient
      was a 65 years old man and presented with a diffuse enlargement of the penis as
      the initial sign, followed by erosive ulcer in the caput penis and inguinal
      lymphadenectasis. The tumor was pathohistologically manifested as an epidermal
      ulcer, with tumorous necrosis around the capillary, infiltrative growth and
      atypical changes of the neoplastic cells and proliferation of capillaries.
      Immunohistochemically, the tumor cells were positive for CD43 and CD3, but
      negative for CD20, CD79a, CD34, CD30, CD56 and CD34. Clinically it responded to
      the chemotherapy designed for peripheral T-cell lymphoma. CONCLUSION: Primary
      peripheral T-cell lymphoma of the penis is an extremely rare malignant tumor, the
      diagnosis of which relies on histopathological examination, immunohistochemical
      staining and differentiation between squamous cell carcinoma and other types of
      lymphoma.

PMID- 19102502
TI  - [Comparison of the methods of separating high-quality sperm for intrauterine
      insemination].
AB  - OBJECTIVE: To analyze and compare the pregnancy rates of intrauterine
      insemination (IUI) achieved by 3 optimized methods of separating high-quality
      sperm. METHODS: The data from 452 infertile couples who underwent 671 IUI cycles
      in our reproductive medicine center were retrospectively analyzed. The patients
      were divided into three groups: 5% HSA Earle's swim-up, SpermRinse swim-up and
      SupraSperm density gradient centrifugation according to different methods for
      separating high-quality sperm, and the clinical pregnancy rates were compared.
      RESULTS: In the 5% HSA Earle's swim-up group, 21 pregnancies were achieved in 221
      cycles (9.5%) and in the SpermRinse swim-up group, 34 in 215 cycles (15.8%), with
      a significantly higher rate in the latter than in the former (P < 0.05). In the
      SupraSperm density gradient centrifugation group, there were 34 pregnancies in
      235 cycles (14.5%), with no statistically significant difference from the other
      two groups (P > 0.05). CONCLUSION: The SpermRinse swim-up method can improve the
      clinical pregnancy rate and is suitable for various types of sterile patients.
      SupraSperm density gradient centrifugation, as an effective method available for
      separating high-quality sperm, is particularly suitable for those with lots of
      inflammatory cells and dead and abnormal sperm in the semen.

PMID- 19102503
TI  - [Expressions of MMP-2 and COX-2 mRNA in bladder transitional cell carcinoma and
      their correlation].
AB  - OBJECTIVE: To determine the levels of MMP-2 and COX-2 mRNA in bladder
      transitional cell carcinoma tissues and explore their relationship. METHODS: We
      enrolled in this study 42 patients with bladder transitional cell carcinoma,
      including Ta-T1 (n = 18), T2-T4 (n = 24), G1 (n = 12), G2 (n = 19), G3 (n = 11),
      metastasis (n =26) and non-metastasis (n = 16). Another 5 cases of normal bladder
      tissues were taken as controls, and the levels of MMP-2 and COX-2 mRNA were
      detected by RT-PCR. RESULTS: The relative expressions of COX-2 mRNA were 1.038 +/
      0. 484 in Ta-T1, 1.489 +/- 0.584 in T2-T4, 0.920 +/- 0.442 in G1, 1.338 +/-
      0.584 in G2 and 1.632 +/- 0.515 in G3, all significantly higher than that of the
      controls (0.460 +/- 0.224, P < 0.05). And the corresponding relative levels of
      MMP-2 mRNA were 1.107 +/- 0.384, 1.604 +/- 0.425, 0.971 +/- 0.370, 1.445 +/-
      0.378 and 1.755 +/- 0.387, also significantly higher than that of the latter
      group (0.423 +/- 0.227, P < 0.05). The COX-2 and MMP-2 mRNA levels in the tumor
      tissues with and without metastasis were 1.591 +/- 0.455 vs 0.815 +/- 0.430 and
      1.676 +/- 0.339 vs 0.927 +/- 0.228, (P < 0.01), respectively, with a positive
      correlation between the mRNA level of COX-2 and that of MMP-2 (r = 0. 703, P <
      0.01). CONCLUSION: MMP-2 and COX-2 mRNA are highly expressed in bladder
      transitional cell carcinoma tissues and their expressions are positively
      correlated with the degree of malignancy. MMP-2 and COX-2 might play a synergetic
      role in the pathogenesis and progression of bladder transitional cell carcinoma.

PMID- 19102504
TI  - [A preliminary study of pre-analysis quality control for semen analysis].
AB  - OBJECTIVE: To discuss how some pre-analysis processes influence the results of
      semen analysis and how to minimize their influence on the accuracy of laboratory
      results based on the concept of total quality management (TQM). METHODS: We
      conducted semen quality analyses for 21 male volunteers, who had abstained from
      tobacco and alcohol for over 72 days for the purpose of fertilization, before and
      after the abstinence, and obtained their seminal parameters at 0.5, 1, 2 and 3
      hours after semen sample collection. RESULTS: Sperm concentration, sperm motility
      and the percentage of grade a + b sperm were significantly higher after the
      abstinence of tobacco and alcohol than before (P < 0.01). With the lengthening of
      post-ejaculation time, there was a significant decrease in sperm motility and the
      percentage of grade a + b sperm (P < 0.05), but not in sperm concentration (P >
      0.05). CONCLUSION: A lot of factors may affect the results of semen analysis,
      including the subjects' habits of drinking and smoking and the length of time
      after semen collection. Therefore, every procedure of semen analysis has to be
      dealt with very carefully so as to meet the requirements of TQM and achieve most
      reliable results for clinical use.

PMID- 19102505
TI  - [Influence of sperm DNA damage on reproductive outcomes and its clinical
      significance].
AB  - Many factors are responsible for sperm DNA damage, which may lead to
      fertilization failure and embryo maldevelopment. At present, sperm DNA damage can
      be detected by more and more methods, which are considered to be superior to the
      conventional measures. There are some clinical indications for tests of sperm DNA
      damage in IVF/ICSI, but additional studies are still needed to fully define the
      clinical value of testing sperm DNA damage.

PMID- 19102506
TI  - [Glutathione and male reproduction].
AB  - Reduced glutathione (GSH) , the most abundant non-protein thiol in mammalian
      cells, exists extensively in the human body and plays a key role in many
      biological processes, including the synthesis of proteins and DNA and the
      transport of amino acids, especially in protecting cells against oxidation. GSH
      also shows its important clinical value in the treatment of many diseases. It has
      been reported that GSH also widely exists in the male reproductive system and has
      a therapeutic role in male infertility. The objective of this review is to
      summarize the distribution of GSH in the male reproductive system and its
      therapeutic value for male infertility.

PMID- 19102507
TI  - [Advances in researches on epididymal WFDC-type serine protease inhibitors].
AB  - Sperm maturation in the epididymis is regulated by changes of luminal ion
      concentration and processing of sperm surface membrane by several glycosidases
      and proteases, and the actions of the proteases are controlled by protease
      inhibitors present in specific areas of the epididymis. WFDC-type serine protease
      inhibitors that are highly expressed in the epididymis play an important role in
      natural immunity and male reproduction. This paper gives an overview of the
      structure and function of the protein and its application prospects in the
      development of drugs for male reproductive tract infection and
      immunocontraception.

PMID- 19102508
TI  - [Cyclooxygenase-2 and cyclooxygenase-2 inhibitors in prostate cancer].
AB  - Cyclooxygenase-2 (Cox-2) is over-expressed in prostate cancer (PCa) and involved
      in its development and progression by facilitating inflammatory response,
      reducing cell apoptosis, increasing angiogenesis and damaging DNA oxidation.
      Selective Cox-2 inhibitors suppress PCa growth through various channels and
      therefore have a promising application value in the management of prostate
      cancer.

PMID- 19102509
TI  - [Development and status quo of testis transplantation].
AB  - A lot of advances have been made in testis autotransplantation, testis
      homotransplantation, testicular tissue transplantation, Leydig cell
      transplantation and spermatogonial stem cell transplantation in the past decades.
      And recent years, have witnessed remarkable progress in Leydig cell
      transplantation and spermatogonial stem cell transplantation, which promise to be
      new means for the treatment of male infertility and hypogonadism. The development
      and present state of testis transplantation are summarized in this paper based on
      the related literature of recent years.

PMID- 19102510
TI  - [Shengjing granule: an effective Chinese medicine for spermatogenic disturbance
      in mice].
AB  - OBJECTIVE: To observe the effect of the Chinese medicine Shengjing Granule on
      spermatogenic disturbance in mice. METHODS: Forty-six male Kunming mice were
      randomly divided into a normal (n = 10), a model (n = 12), a control (n = 12) and
      a Shengjing group (n = 12), and models of spermatogenic disturbance were
      established by intraperitoneal injection of cyclophosphamide in the latter three.
      Then the first two groups received intragastric administration of physiological
      saline and the second two that of clomiphene (21.6 mg/kg x d) and Shengjing
      Granule (16 g/kg x d), respectively, all for 15 days. On the following day, the
      testis weight was measured, the levels of the follicle stimulating hormone (FSH),
      the luteinizing hormone (LH) and testosterone (T) determined by radioimmunoassay.
      Histological observations were made of the testis tissues under the microscope.
      RESULTS: The testis index and T level were (3.958 +/- 0.342) g/kg and (7.046 +/-
      0.291) nmo/L, obviously increased, while the levels of FSH and LH were (2.947 +/-
      0.587) mIU/ml and (3.254 +/- 0.492) mIU/ml, significantly decreased, in the
      Shengjing group, as compared with (3.525 +/- 0.462) g/kg, (6.231 +/- 0.317)
      nmol/L, (5.428 +/- 0.719) mIU/ml and (5.155 +/- 0.460) mIU/ml in the model group
      (P < 0.05). The number of spermatogenic cells on the seminiferous tubules and
      that of sperm in the lumina of the tubules were markedly increased in the
      Shenginjg group, compared with the models. CoCONCLUSIONShenginjg Granule is
      effective for spermatogenic disturbance in mice.

PMID- 19102512
TI  - Black cohosh for the management of menopausal symptoms : a systematic review of
      clinical trials.
AB  - Alternative medicine preparations represent a significant industry worldwide.
      Black cohosh (Cimicifuga racemosa), a buttercup plant grown in North America, is
      one such popular preparation for the treatment of menopausal symptoms. Because
      the proportion of women experiencing climacteric symptoms is high, black cohosh
      merits further study as to its efficacy and safety. Convincing evidence for its
      efficacy in this setting remains to be demonstrated. The purpose of this
      systematic review was to assess the current literature on the benefits of black
      cohosh for women experiencing climacteric symptoms. To this end, a PubMed search
      was conducted on 1 November 2007 using the search terms 'black cohosh' AND
      'menopause'. The search was limited to randomized controlled trials in the
      English language involving adults. Several additional reviews dealing with
      alternative therapies for menopause were included to capture additional older and
      non-English language literature. Ultimately, 16 studies eligible for review were
      identified. Many of the studies had conflicting results. Methodological flaws
      included lack of uniformity of the drug preparation used, variable outcome
      measures and lack of a placebo group. The benefits of black cohosh in the
      management of climacteric symptoms remain to be proven. Case studies suggest an
      additional unexplored area of adverse events that also needs to be addressed.

PMID- 19102511
TI  - Complexities of diagnosis and treatment of allergic respiratory disease in the
      elderly.
AB  - Atopic diseases such as rhinitis and asthma are relatively common in children and
      young adults. However, many patients aged >65 years are also affected by these
      disorders. Indeed, the literature suggests that between 3-12% and 4-13% of
      individuals in this age range have allergic rhinitis and asthma, respectively.
      However, these numbers are most likely underestimates because atopic diseases are
      frequently not considered in older patients. The diagnosis of both allergic
      rhinitis and asthma in older patients is more difficult than in younger patients
      because of a wide differential diagnosis of other diseases that can produce
      similar symptoms and must be excluded. Furthermore, treatment of these disorders
      is complicated by the potential for drug interactions, concern about the adverse
      effects of medications, in particular corticosteroids, and the lack of drug
      trials specifically targeting treatment of older patients with allergic rhinitis
      and asthma.

PMID- 19102513
TI  - Pharmacists' interventions for optimization of medication use in nursing homes :
      a systematic review.
AB  - The elderly use more medications than younger adults. In addition, the prevalence
      of inappropriate prescribing is high in nursing homes. The aim of this review was
      to collect and interpret the results of clinical studies of interventions
      involving pharmacists aimed at improving the quality of prescribing in nursing
      homes, and to identify the key elements for a successful intervention. To this
      end, we searched MEDLINE, International Pharmaceutical Abstracts and EMBASE from
      January 1987 to May 2008. Studies were selected that (i) involved a pharmacist;
      (ii) took place in the nursing home setting; (iii) involved residents aged > or
      =65 years; (iv) included residents with a range of diseases (not targeted at a
      specific pathology); (v) were controlled trials (randomized or not). The search
      strategy retrieved eight controlled studies that fitted the inclusion criteria. A
      meta-analysis was not possible because of the difference in outcomes chosen in
      the publications. We found mixed evidence for the effectiveness of various
      interventions by pharmacists on pharmacotherapy in the nursing home setting.
      Pharmacists can have different roles in the nursing home such as performing
      regular medication reviews, being an active member of a multidisciplinary team
      and/or educating physicians, nurses and other nursing home staff about medication
      use. Our review shows that the available evidence is mixed concerning the
      effectiveness of interventions by pharmacists on pharmacotherapy in the nursing
      home setting. At the same time, greater pharmacist involvement has been shown in
      published studies to increase physicians' and nurses' knowledge and awareness
      about medication. Evidence is scarce, however, and there is a need for large,
      well conducted randomized controlled trials in the nursing home setting.
      Attention should be paid to the choice of outcome measures and to
      multidisciplinary collaboration when assessing the effects of pharmacists'
      interventions on medication use in nursing homes.

PMID- 19102514
TI  - Self-medication in older urban mexicans : an observational, descriptive, cross
      sectional study.
AB  - BACKGROUND: Self-medication in older adults can be problematic, especially if
      remedies taken without prescription interact with prescribed medications or if
      they produce adverse effects. Before designing interventions to improve self
      medication, it is important to characterize patterns of self-medicating in local
      populations. This can be easily achieved through the conduct of simple surveys.
      OBJECTIVE: To quantify and describe the demographic, socioeconomic and
      pharmacological characteristics of self-medication among a geriatric urban
      population in Chiapas, Mexico. METHODS: An observational, descriptive, cross
      sectional study was conducted, using a conglomerate sampling technique. A total
      of 245 older (aged > or =65 years) residents in the downtown area of Tuxtla
      Gutierrez (Chiapas, Mexico) participated in the study. Information on self
      medication and demographic and socioeconomic variables was obtained from a
      specific structured interview that was conducted by a single specially trained
      physician. RESULTS: More than half of the 245 interviewed older adults (131
      [53.5%; 95% CI 47.2, 59.7]) reported taking a medicine without prescription
      during the last 30 days. Self-medication was significantly more frequent among
      older adults who lived alone compared with married people (p = 0.0274) and among
      the illiterate or those with a low level of education compared with people with
      secondary and high-school degrees (p = 0.0036). NSAIDs (36.2% of medications) and
      antihistamines (12.6%) were the most frequent drugs taken as self-medication. The
      most frequently cited reasons for self-medicating were muscle and joint pain
      (19.9% of medications), upper respiratory tract problems (15.9%) and cough
      (7.3%). However, 13% of people who self-medicated took a remedy for hypertension
      (11% of all medications) without medical supervision. Previous prescriptions
      could have served as the basis for future self-medication in 33 (25.2%) patients.
      Finally, 35 (26.7%) patients who self-medicated reported that they had
      experienced adverse effects from the drug they were taking. CONCLUSION: Self
      medication in older adults is a problem that should be carefully addressed in
      public health policies. Surveys such as the present one are easy to carry out
      (and could conveniently be conducted in primary care settings), rapidly yield
      information about the true nature of self-medication in local populations, and
      provide a basis on which to design future interventions. Factors associated with
      self-medication in this study, including both socioeconomic characteristics (e.g.
      most self-medicators were poorly educated or lived alone) and therapeutic
      considerations (e.g. substantial proportions of patients self-medicated for
      hypertension, used previous prescriptions as the basis for self-medication, or
      reported adverse effects of self-medication), are vital clues to the design of
      effective and appropriately targeted interventions in the future.

PMID- 19102515
TI  - Olmesartan medoxomil in elderly patients with essential or isolated systolic
      hypertension : efficacy and safety data from clinical trials.
AB  - BACKGROUND: The appearance and progression of essential hypertension is
      associated with increasing age. Older patients also frequently have an abnormally
      elevated systolic blood pressure (SBP) [> or =140 mmHg] without an elevated
      diastolic blood pressure (DBP) [< or =90 mmHg], a phenomenon known as isolated
      systolic hypertension. Thus, management of hypertension in elderly patients
      requires agents that can effectively treat isolated systolic hypertension as well
      as essential hypertension. OBJECTIVE: The aim of this analysis was to assess the
      efficacy and safety of the angiotensin II type 1 receptor antagonist (angiotensin
      receptor blocker [ARB]) olmesartan medoxomil in elderly patients with either
      essential hypertension or isolated systolic hypertension. METHODS: Efficacy data
      were obtained from two studies and safety data from an Integrated Summary of
      Safety. The efficacy of individually optimized doses of olmesartan medoxomil 20
      or 40 mg/day, with or without hydrochlorothiazide, in elderly patients (> or =65
      years) was assessed in two separate randomized, double-blind studies. One study
      assessed DBP changes in 251 patients with essential hypertension (mean seated DBP
      [seDBP] 100-114 mmHg and mean seated SBP [seSBP] >150 mmHg); the other study
      evaluated SBP changes in 256 patients with isolated systolic hypertension (mean
      seSBP >160 mmHg and mean seDBP <90 mmHg). Safety and tolerability were assessed
      in each study and in an Integrated Summary of Safety, which comprised data from
      1646 hypertensive patients aged > or =65 years. RESULTS: In patients with
      essential hypertension, 12 weeks of treatment reduced mean seDBP (primary
      efficacy parameter) by 17.9 mmHg; mean seSBP was also significantly reduced. At
      study end (week 52), the proportion of diastolic responders (seDBP < or =90 mmHg)
      was 93%. In patients with isolated systolic hypertension, mean seSBP was reduced
      by 30.0 mmHg at week 12 (primary efficacy parameter); mean seDBP was only
      slightly reduced. At study end (week 24), the proportion of systolic responders
      (seSBP < or =135 mmHg) was 62.5%. Reductions in blood pressure (BP) were
      maintained throughout treatment in both patient populations. In each study,
      doubling the olmesartan medoxomil dose from 20 to 40 mg/day or adding
      hydrochlorothiazide delivered additional BP-lowering efficacy without any
      tolerability concerns, and the Integrated Summary of Safety also showed that
      olmesartan medoxomil with or without hydrochlorothiazide was well tolerated.
      Efficacy and safety results were similar in elderly (65-74 years) and very
      elderly (> or =75 years) patients. CONCLUSION: Olmesartan medoxomil provides
      effective and well tolerated control of hypertension in elderly patients with
      either essential hypertension or isolated systolic hypertension.

PMID- 19102516
TI  - Factors associated with bleeding in elderly hospitalized patients treated with
      enoxaparin sodium : a prospective, open-label, observational study.
AB  - BACKGROUND: Despite a lack of clear recommendations to guide decision-making,
      reductions in enoxaparin sodium dosage in the elderly and in patients with mild
      and moderate renal dysfunction are common in patients with acute coronary
      syndrome. OBJECTIVE: To evaluate whether weight, age and renal function are
      associated with anti-factor Xa activity and with bleeding in elderly patients
      treated with enoxaparin sodium. METHOD: This was a prospective observational
      study of 156 elderly patients admitted consecutively to a general internal
      medicine ward with creatinine clearance >30 mL/min who were treated with
      enoxaparin sodium twice daily. Anti-factor Xa activity and bleeding events were
      documented in all patients. Statistical analyses were conducted to determine the
      effects of clinical characteristics such as renal dysfunction, age and bodyweight
      on these parameters. RESULTS: 156 patients (60% males, mean age 71.0 +/- 15.98
      years) were studied. Therapeutic anti-factor Xa was observed in 85.3% of patients
      treated with enoxaparin sodium 0.61-0.8 mg/kg/12h, and in 82.6% of patients
      treated with enoxaparin sodium 0.81-1.1 mg/kg/12h. Minor or major bleeding was
      observed in 5.8% of patients, and was associated with a lower mean bodyweight
      (61.89 +/- 13.35 vs 74.30 +/- 13.24 kg for patients with no bleeding; p = 0.014).
      Bodyweight < or =55 kg was associated with bleeding with an odds ratio of 5.63
      (95% CI 1.2, 25, p = 0.025). CONCLUSION: Low bodyweight is associated with a
      greater risk of bleeding despite a reduction in enoxaparin sodium dose according
      to weight. This finding supports the possibility that low bodyweight is an
      independent risk factor for enoxaparin sodium-related bleeding.

PMID- 19102517
TI  - Modulation of human peripheral blood mononuclear cell proliferative response by
      diltiazem : in vitro comparison in younger versus older subjects.
AB  - BACKGROUND: The gradual aging of population has increased the number of elderly
      patients receiving kidney transplants. In elderly transplant recipients, careful
      immunosuppression has to be maintained to avoid both rejection and adverse
      effects. Clinical protocols after kidney transplantation include use of the
      calcium channel antagonist diltiazem to ameliorate the hypertensive effect and
      nephrotoxicity of the immunosuppressant agent ciclosporin (cyclosporine).
      OBJECTIVE: Since immune response can be impaired by senescence, we evaluated the
      influence of diltiazem on lymphocyte proliferation both alone and in the presence
      of ciclosporin in younger versus older subjects. METHODS: Peripheral blood
      mononuclear cells (PBMC) from younger healthy donors (aged 19-24 years) and older
      subjects (aged 59-65 years) were isolated and stimulated with mitogens,
      recombinant human interleukin-2 (IL-2), purified protein derivative (PPD) antigen
      from Mycobacteriumtuberculosis, and anti-CD3 monoclonal antibody (alphaCD3 moAb)
      in the presence or absence of 10(-4), 10(-5), 10(-6), 10(-7) mol/L concentrations
      of diltiazem. In some experiments, lymphocytes from younger and older subjects
      were used as responder cells in an allogeneic mixed lymphocyte reaction (MLR) in
      the presence of different concentrations of diltiazem and 10 ng/mL of
      ciclosporin. RESULTS: We found that PBMC from older subjects were more
      susceptible to immunosuppression induced by low concentrations of diltiazem when
      mitogens were used to stimulate cells. In particular, when pokeweed mitogen was
      used, diltiazem 10(-7) mol/L was associated with statistically significant
      immunosuppression in older subjects compared with younger subjects. This effect
      was not observed when IL-2, PPD antigen and alphaCD3 moAb were used as
      stimulators. Moreover, in the allogeneic MLR, we found no differences between
      younger and older subjects when the 10(-)(5), 10(-)(6) and 10(-7) mol/L
      concentrations of diltiazem were used alone or in the presence of ciclosporin.
      Only addition of the supratherapeutic 10(-4) mol/L concentration of diltiazem to
      ciclosporin was associated with statistically significant immunosuppression in
      older versus younger subjects. DISCUSSION: Our results show that PBMC from older
      subjects are no more susceptible than PBMC from younger subjects to therapeutic
      doses of diltiazem when T-cell receptors are directly or indirectly involved. On
      the contrary, when PBMC activation was not mediated by T-cell receptor
      involvement, as in the case of pokeweed mitogen, susceptibility to a therapeutic
      concentration of diltiazem in older subjects was enhanced. Moreover, co
      administration of therapeutic doses of diltiazem and ciclosporin in an MLR showed
      no significant differences between younger and older subjects in an in vitro
      model of lymphocyte response to allogeneic transplantation. CONCLUSION: Since we
      found no variations in immunosuppression between older and younger subjects when
      therapeutic doses of diltiazem were added to ciclosporin, our data do not
      discourage the use of diltiazem in older kidney transplant recipients receiving
      ciclosporin therapy.

PMID- 19102519
TI  - The ground state correlation energy of the random phase approximation from a ring
      coupled cluster doubles approach.
AB  - We present an analytic proof demonstrating the equivalence between the random
      phase approximation (RPA) to the ground state correlation energy and a ring
      diagram simplification of the coupled cluster doubles (CCD) equations. In the CCD
      framework, the RPA equations can be solved in O(N(4)) computational effort, where
      N is proportional to the number of basis functions.

PMID- 19102520
TI  - Enabling ab initio Hessian and frequency calculations of large molecules.
AB  - A linear scaling method, termed as cardinality guided molecular tailoring
      approach, is applied for the estimation of the Hessian matrix and frequency
      calculations of spatially extended molecules. The method is put to test on a
      number of molecular systems largely employing the Hartree-Fock and density
      functional theory for a variety of basis sets. To demonstrate its ability for
      correlated methods, we have also performed a few test calculations at the Moller
      Plesset second order perturbation theory. A comparison of central processing unit
      and memory requirements for medium-sized systems with those for the corresponding
      full ab initio computation reveals substantial gains with negligible loss of
      accuracy. The technique is further employed for a set of larger molecules,
      Hessian and frequency calculations of which are not possible on commonly
      available personal-computer-type hardware.

PMID- 19102521
TI  - Vibrational energy levels of CH5(+).
AB  - We present a parallelized contracted basis-iterative method for calculating
      numerically exact vibrational energy levels of CH(5)(+) (a 12-dimensional
      calculation). We use Radau polyspherical coordinates and basis functions that are
      products of eigenfunctions of bend and stretch Hamiltonians. The bend
      eigenfunctions are computed in a nondirect product basis with more than 200x10(6)
      functions and the stretch functions are computed in a product potential optimized
      discrete variable basis. The basis functions have amplitude in all of the 120
      equivalent minima. Many low-lying levels are well converged. We find that the
      energy level pattern is determined in part by the curvature and width of the
      valley connecting the minima and in part by the slope of the walls of this valley
      but does not depend on the height or shape of the barriers separating the minima.

PMID- 19102522
TI  - Extrapolation to the complete-basis-set limit and the implications of avoided
      crossings: The X 1Sigma(g)+, B 1Delta(g), and B' 1Sigma(g)+ states of C2.
AB  - The uniform singlet- and triplet-pair extrapolation scheme and its generalized
      variant are utilized to describe bond breaking of the C(2) molecule in the ground
      electronic state, as well as in two other excited states of the same spin
      symmetry by extrapolating multireference configuration interaction energies
      calculated with the correlation consistent basis sets of Dunning to the complete
      basis set limit. It is shown that the correlation energy changes drastically
      (with a symmetric sigmoidal-type shape) near the geometry (R approximately 1.6 A)
      where the two lowest (1)Sigma(g)(+) adiabatic states show the avoided crossing.
      The implications of such a feature on extrapolating the dynamical correlation are
      then analyzed, and the attributes of the extrapolated ground electronic state
      shown to be in excellent agreement with the most recent experimental data
      available in the literature.

PMID- 19102523
TI  - P3M algorithm for dipolar interactions.
AB  - An extension to the P(3)M algorithm for electrostatic interactions is presented
      that allows to efficiently compute dipolar interactions in periodic boundary
      conditions. Theoretical estimates for the root-mean-square error of the forces,
      torques, and the energy are derived. The applicability of the estimates is tested
      and confirmed in several numerical examples. A comparison of the computational
      performance of the new algorithm to a standard dipolar-Ewald summation methods
      shows a performance crossover from the Ewald method to the dipolar P(3)M method
      for as few as 300 dipolar particles. In larger systems, the new algorithm
      represents a substantial improvement in performance with respect to the dipolar
      standard Ewald method. Finally, a test comparing point-dipole-based and charged
      pair based models shows that point-dipole-based models exhibit a better
      performance than charged-pair based models.

PMID- 19102524
TI  - Crystal structure prediction of LiBeH3 using ab initio total-energy calculations
      and evolutionary simulations.
AB  - The stable crystal structure of LiBeH(3) is predicted on the basis of ab initio
      total-energy calculations using density-functional theory and an extended
      database of candidate structures and using global optimizations based on an
      evolutionary algorithm. At the level of density-functional theory, a CaSiO(3)_1
      type structure with space group P2(1)/c, containing BeH(4) tetrahedra linked in
      chains, is the ground-state structure of LiBeH(3) (alpha-LiBeH(3)). It is found
      to be lower in energy than the structures proposed in previous studies. The
      analysis of the electronic structure shows that alpha-LiBeH(3) is an insulator
      with a band gap of about 4.84 eV and exhibits strong covalent bonding in the
      BeH(4) tetrahedral complexes. Calculations at finite temperatures and high
      pressures suggest that at T=408 K and ambient pressure a structural transition
      from alpha-LiBeH(3) (CaSiO(3)-type) to a YBO(3)-type structure with space group
      Cmcm occurs and that at a pressure of 7.1 GPa alpha-LiBeH(3) undergoes a pressure
      induced structural transition from the alpha-phase to a MgSiO(3)-type structure
      with space group C2/c. The calculated enthalpies of formation (-45.36 and -30.12
      kJ/mol H(2) without and with zero-point energy corrections) are in good agreement
      with the experimental result, indicating that LiBeH(3) is a potential hydrogen
      storage material with low activation barriers for hydrogen desorption.

PMID- 19102525
TI  - Block correlated coupled cluster method with a complete-active-space self
      consistent-field reference function: the implementation for low-lying excited
      states.
AB  - Block correlated coupled cluster theory with the complete-active-space self
      consistent-field reference function (CAS-BCCC) is generalized for low-lying
      electronic excited states. By truncating the cluster operator up to the four
      block correlation level, the corresponding CAS-BCCC4 method for excited states
      has been efficiently implemented. The approach is applied to study the excited
      state potential energy surfaces for HF and C(2) and to evaluate adiabatic or
      vertical excitation energies for CH(2), N(2), and trans-1,3-butadiene. The
      results are compared with those from the full configuration interaction, the
      internally contracted multireference configuration interaction with singles and
      doubles, the complete active space with second-order perturbation theory, and
      other theoretical methods (if available). The CAS-BCCC4 approach is found to
      provide high accuracy calculations for the low-lying excited states of the
      systems under study.

PMID- 19102526
TI  - An ab initio/Rice-Ramsperger-Kassel-Marcus prediction of rate constant and
      product branching ratios for unimolecular decomposition of propen-2-ol and
      related H + CH2COHCH2 reaction.
AB  - Enols have been found to be important intermediates in the combustion flames of
      hydrocarbon [C. A. Taatjes et al., Science 308, 1887 (2005)]. The removal
      mechanism of enols in combustion flame has not been established yet. In this
      work, the potential energy surface for the unimolecular decomposition of syn
      propen-2-ol and H + CH(2)COHCH(2) recombination reactions have been first
      investigated by CCSD(T) method. The barrier heights, reaction energies, and
      geometrical parameters of the reactants, products, intermediates, and transition
      states have been investigated theoretically. The results show that the formation
      of CH(3)CO + CH(3) via the CH(3)COCH(3) intermediate is dominant for the
      unimolecular decomposition of syn-propen-2-ol and its branching ratio is over 99%
      in the whole temperature range from 700 to 3000 K, and its rate constant can be
      expressed as an analytical form in the range of T=700-3000 K at atmospheric
      pressure. This can be attributed to the lower energy barrier of this channel
      compared to the other channels. The association reaction of H with CH(2)COHCH(2)
      is shown to be a little more complicated than the unimolecular decomposition of
      syn-propen-2-ol. The channel leading to CH(3)CO + CH(3) takes a key role in the
      whole temperature range at atmospheric pressure. However at the higher pressure
      of 100 atm, the recombination by direct formation of syn-propen-2-ol through H
      addition is important at T<1000 K. In the range of T>1400 K, the recombination
      channel leading to CH(3)CO + CH(3) turns out to be significant.

PMID- 19102527
TI  - Long-range multipolar potentials of the 18 spin-orbit states arising from the
      C(3P) + OH(X 2Pi) interaction.
AB  - We present multipolar potentials at large intermolecular distances for the 18
      doubly degenerate spin-orbit states arising from the interaction between the two
      open-shell systems, C((3)P) and OH(X (2)Pi). With OH fixed at its ground
      vibrational state-averaged distance r(0), the long-range potentials are two
      dimensional potential energy surfaces (PESs) that depend on the intermolecular
      distance R and the angle gamma = CGH, where G represents the mass center of OH.
      The 18x18 diabatic potential matrix elements are built up from the perturbation
      theory up to second order and from a two-center expansion of the Coulombic
      interaction potential, resulting in a multipolar expansion of the potential
      expressed as a series of terms varying in R(-n). The expressions for the long
      range coefficients of the expansion are explicitly given in terms of monomer
      properties such as permanent multipole moments, and static and dynamic
      polarizabilities. Accurate values for the monomer properties are used to properly
      determine the long-range interaction coefficients. The diagonalization of the
      full 18x18 potential matrix generates adiabatic long-range PESs in good agreement
      with their ab initio counterparts.

PMID- 19102528
TI  - Double photoionization of thiophene and bromine-substituted thiophenes.
AB  - We report the double photoionization spectra of thiophene, 3-bromothiophene, and
      3,4-dibromothiophene using a coincidence spectroscopy technique based on electron
      time-of-flight measurements. Spectra have been recorded between the onset and
      40.814 eV using He IIalpha radiation. The He I photoelectron spectrum of 3,4
      dibromothiophene has also been measured. All the spectra have been analyzed and
      interpreted in detail on the basis of theoretical simulations from accurate
      Green's function calculations.

PMID- 19102529
TI  - Fast vibrational calculation of anharmonic OH-stretch frequencies for two low
      energy noradrenaline conformers.
AB  - We introduce a new reduced-coupling technique to accelerate direct calculations
      of a selected number of vibrational frequencies in large molecular systems. Our
      method combines the advantages of the single-to-all correlation-corrected
      vibrational self-consistent field (STA-CC-VSCF) approach [D. M. Benoit, J. Chem.
      Phys. 125, 244110 (2006)] with those of the fast-CC-VSCF technique [D. M. Benoit,
      J. Chem. Phys. 120, 562 (2004)] and allows the ab initio calculation of only the
      relevant parts of the required potential energy surface (PES). We demonstrate,
      using a set of five aliphatic alcohol molecules, that the new fast-STA-CC-VSCF
      method is accurate and leads to very substantial time gains for the computations
      of the PES. We then use the fast-STA-CC-VSCF method to accelerate the computation
      of the OH-stretch and NH-stretch frequencies of the two lowest-energy conformers
      of noradrenaline, namely, AG1a and GG1a. Our new approach enables us to run the
      calculation 89 times faster than the standard CC-VSCF technique and makes it
      possible to use a high-level MP2/TZP description of the PES. We demonstrate that
      the influence of the strong mode-mode couplings is crucial for a realistic
      description of the particular OH-stretch vibrational signature of each conformer.
      Finally, of the two possible low-energy conformers, we identify AG1a as the one
      most likely to have been observed in the experiments of Snoek et al. [Mol. Phys.
      101, 1239 (2003)].

PMID- 19102530
TI  - Pulse-train control of branching processes: elimination of background and
      intruder state population.
AB  - The authors introduce and describe pulse train control (PTC) of population
      branching in strongly coupled processes as a novel control tool for the
      separation of competing multiphoton processes. Control strategies are presented
      based on the different responses of processes with different photonicities and/or
      different frequency detunings to the pulse-to-pulse time delay and the pulse-to
      pulse phase shift in pulse trains. The control efficiency is further enhanced by
      the property of pulse trains that complete population transfer can be obtained
      over an extended frequency range that replaces the resonance frequency of simple
      pulses. The possibility to freely tune the frequency assists the separation of
      the competing processes and reduces the number of subpulses required for full
      control. As a sample application, PTC of leaking multiphoton resonances is
      demonstrated by numerical simulations. In model systems exhibiting sizable
      background (intruder) state population if excited with single pulses, PTC leading
      to complete accumulation of population in the target state and elimination of
      background population is readily achieved. The analysis of the results reveals
      different mechanisms of control and provides clues on the mechanisms of the
      leaking process itself. In an alternative setup, pulse trains can be used as a
      phase-sensitive tool for level switching. By changing only the pulse-to-pulse
      phase shift of a train with otherwise unchanged parameters, population can be
      transferred to any of two different target states in a near-quantitative manner.

PMID- 19102531
TI  - IR/UV spectroscopy on jet cooled 3-hydroxyflavone (H2O)n (n = 1,2) clusters along
      proton transfer coordinates in the electronic ground and excited states.
AB  - The structure and reactivity of isolated 3-hydroxyflavone (3-HF) aggregates with
      one and two water molecules has been investigated by applying combined
      infrared/ultraviolet (IR/UV) spectroscopy in a supersonic jet both for the
      electronic ground and excited states. In combination with density functional
      theory (DFT) calculations, the IR spectra of the S(0) states recorded from the
      upper fingerprint region to the OH stretching vibrations are assigned to the most
      stable isomers of the clusters. For the first electronically excited (pi pi(*))
      state of the 3-HF(H(2)O)(2) cluster structural information are obtained from the
      IR spectra in combination with time-dependent-DFT (TD-DFT) calculations. No
      proton transfer structure is observed in the case of a low excess energy within
      the electronically excited state. By raising the excitation energy, additional
      bands appear that can be assigned to a tautomeric form indicating the induction
      of a proton transfer reaction.

PMID- 19102532
TI  - Effect of an external electric field on the diffusion-influenced reversible
      reaction of a neutral particle and a charged particle in three dimensions.
AB  - The diffusion-influenced reversible reaction of a neutral particle and a charged
      particle in an external field is analytically solved in three dimensions. A
      generalized nonisotropic boundary condition is used and a kinetic equation for
      the probability density function is set up. A tridiagonal matrix equation is
      derived for the coefficients of the series solution and we obtain the solution
      within the diagonal approximation in the Laplace domain. We also find that the
      long time asymptotic behavior of the first term solution shows a kinetic
      transition from a power law to an exponential behavior as the field strength is
      increased. The full numerical calculation reveals that the first term solution
      deviates slightly at short times but gives good result at long times. Thus it
      contributes dominantly to the kinetic transition behavior at long times. For the
      irreversible limit, we find a different kinetic transition behavior from a power
      law to an exponential increase through a constant in the transition region for
      the initially bound state.

PMID- 19102533
TI  - Solving the structure of reaction intermediates by time-resolved synchrotron x
      ray absorption spectroscopy.
AB  - We present a robust data analysis method of time-resolved x-ray absorption
      spectroscopy experiments suitable for chemical speciation and structure
      determination of reaction intermediates. Chemical speciation is done by principal
      component analysis (PCA) of the time-resolved x-ray absorption near-edge
      structure data. Structural analysis of intermediate phases is done by theoretical
      modeling of their extended x-ray absorption fine-structure data isolated by PCA.
      The method is demonstrated using reduction and reoxidation of Cu-doped ceria
      catalysts where we detected reaction intermediates and measured fine details of
      the reaction kinetics. This approach can be directly adapted to many time
      resolved x-ray spectroscopy experiments where new rapid throughput data
      collection and analysis methods are needed.

PMID- 19102535
TI  - Demixing in binary mixtures of apolar and dipolar hard spheres.
AB  - We study the demixing transition of mixtures of equal size hard spheres and
      dipolar hard spheres using computer simulation and integral equation theories.
      Calculations are carried out at constant pressure, and it is found that there is
      a strong correlation between the total density and the composition. The critical
      temperature and the critical total density are found to increase with pressure.
      The critical mole fraction of the dipolar component on the contrary decreases as
      pressure is augmented. These qualitative trends are reproduced by the theoretical
      approaches that on the other hand overestimate by far the value of the critical
      temperature. Interestingly, the critical parameters for the liquid-vapor
      equilibrium extrapolated from the mixture results in the limit of vanishing
      neutral hard sphere concentration agree rather well with recent estimates based
      on the extrapolation of charged hard dumbbell phase equilibria when dumbbell
      elongation shrinks to zero [G. Ganzenmuller and P. J. Camp, J. Chem. Phys. 126,
      191104 (2007)].

PMID- 19102534
TI  - A new crossover sine model based on trigonometric model and its application to
      the crossover lattice equation of state.
AB  - In this study, a new crossover sine model (CSM) n was developed from a
      trigonometric model [M. E. Fisher, S. Zinn, and P. J. Upton, Phys. Rev. B 59,
      14533 (1999)]. The trigonometric model is a parametric formulation model that is
      used to represent the thermodynamic variables near a critical point. Although
      there are other crossover models based on this trigonometric model, such as the
      CSM and the analytical sine model, which is an analytic formulation of the CSM,
      the new sine model (NSM) employs a different approach from these two models in
      terms of the connections between the parametric variables of the trigonometric
      model and thermodynamic variables. In order to test the performance of the NSM,
      the crossover lattice equation of state [M. S. Shin, Y. Lee, and H. Kim, J. Chem.
      Thermodyn. 40, 174 (2008)] was applied using the NSM for correlations of various
      pure fluids and fluid mixtures. The results showed that over a wide range of
      states, the crossover lattice fluid (xLF)/NSM yields the saturated properties of
      pure fluids and the phase behavior of binary mixtures more accurately than the
      original lattice equation of state. Moreover, a comparison with the crossover
      lattice equation of state using the CSM (xLF/CSM) showed that the new model
      presents good correlation results that are comparable to the xLF/CSM.

PMID- 19102536
TI  - Nature of the pressure-induced collapse of an ice clathrate by dielectric
      spectroscopy.
AB  - Collapse of an ice clathrate of type II structure containing tetrahydrofuran as
      guest molecules has been studied at different pressures by dielectric
      spectroscopy. The sample was pressurized to 1.3 GPa at 130 K and the resulting
      collapsed state was pressure cycled. The dielectric relaxation time increases at
      a progressively rapid rate during pressurizing and then decreases slowly on
      depressurizing, but the dielectric relaxation time does not reach the value of
      the original state. With increase in pressure, the limiting high frequency
      permittivity due to orientation of H(2)O molecules first increases by about 5%
      until 0.75 GPa and then decreases slightly until 1 GPa, and finally it increases
      until approximately 1.2 GPa. The decrease is attributed to the loss of
      contribution from the reorientational motion of tetrahydrofuran molecules and the
      increase to densification as the structure mechanically collapses completely in
      the 1-1.25 GPa range. The relaxation time of the collapsed state is comparable
      with that of the high-density amorph formed on pressure collapse of ice.

PMID- 19102537
TI  - Equilibrium sizes and formation energies of small and large Lennard-Jones
      clusters from molecular dynamics: a consistent comparison to Monte Carlo
      simulations and density functional theories.
AB  - We have performed molecular dynamics simulations of Lennard-Jones argon clusters
      in equilibrium with a surrounding vapor and combined them with simulations of
      nucleation events in supersaturated vapor to investigate the dependence of
      critical cluster size on the vapor density in the cluster size range of 20-300
      atoms. The simulations are performed at reduced temperature T(') = 0.662, which
      with the parameter values of Lennard-Jones argon corresponds to 80 K. We obtain
      bulk equilibrium values by simulating a planar liquid-vapor interface. In the
      studied cluster size range, we find a linear relation between critical size Delta
      N(*) and Delta mu(-3), where Delta mu is the chemical potential difference
      between supersaturated vapor and saturated vapor, but the slope of the line is
      not given by the Kelvin relation of classical nucleation theory. With this
      relation, along with the known formation energy of the small critical cluster of
      the nucleation simulations, we proceed to calculate the formation energies for
      larger critical sizes by integrating the nucleation theorem. We compare the
      molecular dynamics results to results from Monte Carlo simulations and both
      perturbative density functional theory and square gradient theory calculations.
      We find that the molecular dynamics results are in excellent agreement with the
      density functional and square gradient values. However, the Monte Carlo critical
      sizes and formation energies are somewhat lower than the molecular dynamics ones.

PMID- 19102538
TI  - Activated instability of homogeneous droplet nucleation and growth.
AB  - For the pure-component supercooled Lennard-Jones vapor, the free energy of
      forming a droplet with a given particle number and volume is calculated using
      density-functional theory. In contrast to what was noted in previous studies, the
      free energy surface beyond the pseudosaddle point no longer exhibits a valley but
      rather channels the nuclei toward a locus of instabilities, initiating an
      unstable growth phase. Similar to a previous study of bubble formation in
      superheated liquids [M. J. Uline and D. S. Corti, Phys. Rev. Lett. 99, 076102
      (2007)], a new picture of homogeneous droplet nucleation and growth emerges.

PMID- 19102539
TI  - The autocorrelation functions of a fluid of molecules interacting through steep
      attractive potentials.
AB  - In a previous paper [G. Rickayzen and D. M. Heyes, J. Chem. Phys. 126, 234503
      (2007)] we investigated by theory and molecular dynamics (MD) simulation the
      force and velocity autocorrelation functions of a fluid of molecules interacting
      through steeply varying potentials of the form phi(r) = 4epsilon[z(2)(r)-z(r)],
      where z(r) = (sigma r)(n), epsilon and sigma set the energy and length scale of
      the interaction, respectively, and n is an adjustable exponent (n = 72 and 144
      were considered in that work). Discrepancies between the theory and simulation
      were found except at the shortest times for some of the state points. In order to
      identify the origin(s) of these discrepancies, we have investigated here another
      fluid, in which the particles interact via the Morse potential in which z(r) =
      exp(-kappa(r-sigma)sigma), where kappa is now the "steepness" parameter. The
      parameter kappa is the analog of n, and this potential form is used in order to
      compare with previous results and establish better the origin of the differences
      between theory and simulation. It is shown in a further development of the theory
      that the actual form of the potential in the steep and short-ranged attractive
      limit is immaterial, and there exists a law of corresponding states for such
      potentials. This conclusion is confirmed by the MD simulations with the two
      potential forms for kappa = n = 144. The difference between the theory and
      simulation correlation functions increases with density, and it is concluded that
      these differences probably originate in many-body effects in time, which are
      absent in the theory. For packing fractions below about 0.2 the agreement between
      the theory and MD simulation force and velocity autocorrelation functions is
      nevertheless very good at all accessible times.

PMID- 19102540
TI  - Raman spectroscopy study of ammonia borane at high pressure.
AB  - Ammonia borane, NH(3)BH(3), has attracted significant interest as a promising
      candidate material for hydrogen storage. The effect of pressure on the bonding in
      NH(3)BH(3) was investigated using Raman spectroscopy to over 20 GPa in a diamond
      anvil cell, and two new transitions were observed at approximately 5 and 12 GPa.
      Vibrational frequencies for the modes of the NH(3) proton donor group exhibited
      negative pressure dependence, which is consistent with the behavior of
      conventional hydrogen bonds, while the vibrational frequencies of the BH(3)
      proton acceptor group showed positive pressure dependence. The observed behavior
      of these stretching modes supports the presence of dihydrogen bonding at high
      pressure. In addition, the BH(3) and NH(3) bending modes showed an increase in
      spectral complexity with increasing pressure together with a discontinuity in d
      nu/d P which suggests rotational disorder in this molecule. These results may
      provide guidance for understanding and developing improved hydrogen storage
      materials.

PMID- 19102541
TI  - Direct observation of the absorption bands of the first electronic transition in
      liquid H2O and D2O by attenuated total reflectance far-UV spectroscopy.
AB  - Absorption bands of the first electronic transition (X (1)A(1)-->A (1)B(1)) of
      water (H(2)O) and heavy water (D(2)O) in the liquid state have been directly
      observed by using a uniquely designed attenuated total reflectance far
      ultraviolet (ATR-FUV) spectrometer. Since the ATR geometry reduces the
      absorbance, the FUV spectra can be obtained over the entire X (1)A(1)-->A (1)B(1)
      absorption band, including the band maxima. Systematic measurements of the FUV
      spectra of H(2)O and D(2)O with heating from 10 to 70 degrees C and the analysis
      of Kramers-Kronig transformation reveal that the first electronic transition band
      redshifted on heating. This result is in good agreement with the redshift that
      has been frequently observed in the low-energy band tail of the X (1)A(1)-->A
      (1)B(1) absorption band.

PMID- 19102543
TI  - Photoionization of isooctane in intense laser fields. II. The effect of
      irradiance on electron dynamics.
AB  - Thin path length jets (60 microm) of liquid isooctane have been photoionized with
      36-70 fs pulses of 3.1 eV photons. Decay of the transient absorption (TA) at 1200
      nm (assigned as predominantly due to absorption by the electron) has been
      examined over a time interval from 0.5 to 40 ps and over an irradiance range from
      7 to 407 TW/cm(2). This range of irradiance covers a region that encompasses the
      closing of the three photon and four photon liquid ionization channels (at
      approximately 15 and 110 TW/cm(2), respectively) [J. Chem. Phys. 127, 214820
      (2007)]. The temporal behavior of the TA is observed to cycle with irradiance. At
      the closing of both channels, the temporal behavior of the TA is the same and can
      be fitted to the model of an electron diffusively recombining with its geminate
      cation. In irradiance regions prior and subsequent to these channel closings, a
      similar diffusive fit of the TA is possible but with parameters changed to
      accommodate an experimental decay, which is much more rapid in the first few
      picoseconds. Possible origins for this periodic behavior are examined using the
      nonperturbative strong field approximation of Riess [Phys. Rev. A 22, 1786
      (1980)].

PMID- 19102542
TI  - Charge transport and glassy dynamics in imidazole-based liquids.
AB  - Broadband dielectric spectroscopy, differential scanning calorimetry, rheology,
      and pulsed field gradient-nuclear magnetic resonance (PFG NMR) are combined to
      study glassy dynamics and charge transport in a homologous series of imidazole
      based liquids with systematic variation of the alkyl chain length. The dielectric
      spectra are interpreted in terms of dipolar relaxation and a conductivity
      contribution. By applying the Einstein, Einstein-Smoluchowski, and Stokes
      Einstein relations, translational diffusion coefficients--in quantitative
      agreement with PFG NMR measurements--are obtained. With increasing alkyl chain
      length, it is observed that the viscosity increases, whereas the structural alpha
      relaxation rate decreases, in accordance with Maxwell's relation. Between the
      rate omega(e) of electrical relaxation and the rate omega(alpha) of the
      structural alpha-relaxation, scaling is observed over more than six decades with
      a decoupling index of about 2.

PMID- 19102544
TI  - High resolution NMR study of T1 magnetic relaxation dispersion. I. Theoretical
      considerations of relaxation of scalar coupled spins at arbitrary magnetic field.
AB  - A theoretical approach to the description of longitudinal (T(1)) relaxation in
      scalar coupled systems of spin 1/2 nuclei at arbitrary magnetic field is
      developed, which is based on the Redfield theory. The consideration is addressed
      to field-cycling relaxometry experiments with high-resolution NMR detection, in
      which the field dependence of T(1)-relaxation times, the nuclear magnetic
      relaxation dispersion (NMRD), can be studied for individual spins of the
      molecule. Our study reveals well-pronounced effects of spin-spin couplings on the
      NMRD curves. First, coupled spins having completely different high-field T(1)
      times tend to relax at low field with a common relaxation time. Second, the NMRD
      curves exhibit sharp features at the fields corresponding to the positions of
      nuclear spin level anticrossings. Such effects of spin-spin couplings show up not
      only for individual spins but also for the T(1)-relaxation of the total spin
      magnetization of the molecule. The influence of spin-spin coupling is of
      importance as long as the coupling strength J is larger than the inverse T(1)
      relaxation times of the spins. Around J x T(1) = 1 there is also a coherent
      contribution to the relaxation kinetics resulting in an oscillatory component of
      the kinetic curves. Application of the theory to experimental examples will be
      described in subsequent publications.

PMID- 19102545
TI  - On the surface of glasses.
AB  - Dynamics near the surface of glasses is generally much faster than in the bulk.
      Neglecting static perturbations of structure at the surface, we use random first
      order transition (RFOT) theory to show the free energy barrier for activated
      motion near a free surface should be half that of the bulk at the same
      temperature. The increased mobility allows the surface layers to descend much
      further on the energy landscape than the bulk ordinarily does. The simplified
      RFOT calculation, however, predicts a limiting value for the configurational
      entropy a vapor deposited glass may reach as a function of deposition rate. We
      sketch how mode coupling effects extend the excess free surface mobility into the
      bulk so that the glass transition temperature is measurably perturbed at depths
      greater than the naive length scale of dynamic cooperativity.

PMID- 19102546
TI  - Stereoselective isomerization of an ensemble of adsorbed molecules with multiple
      orientations: stochastic laser pulse optimization for selective switching between
      achiral and chiral atropisomers.
AB  - We present quantum dynamical simulations for the laser driven isomerization of an
      ensemble of surface mounted stereoisomers with multiple orientations. The model
      system 1-(2-cis-fluoroethenyl)-2-fluorobenzene supports two chiral and one
      achiral atropisomers upon torsion around the C-C single bond connecting phenyl
      ring and ethylene group. An infrared picosecond pulse is used to excite the
      internal rotation around the chiral axis, thereby controlling the chirality of
      the molecule. In order to selectively switch the molecules--independent of their
      orientation on a surface--from their achiral to either their left- or right
      handed form, a stochastic pulse optimization algorithm is applied. The stochastic
      pulse optimization is performed for different sets of defined orientations of
      adsorbates corresponding to the rotational symmetry of the surface. The obtained
      nonlinearly polarized laser pulses are highly enantioselective for each
      orientation.

PMID- 19102547
TI  - Multifunctional metal-doped carbon nanocapsules.
AB  - We present an ab initio study of carbon fullerenes, such as C(20), C(36), C(56),
      C(60), and C(68), that are substitutionally doped with transition metals
      coordinated to several nitrogen atoms. These capsules with porphyrinlike metal
      sites have remarkable electronic and spin polarizations. Additional doping by
      boron increases their highest occupied molecular orbital-lowest unoccupied
      molecular orbital gap, stabilizes their electronic structure, and causes their
      ground states to have higher spin multiplicity, where the spin density is spread
      over the capsule. These capsules could be applied in molecular electronics,
      catalysis, light harvesting, and nanomechanics.

PMID- 19102548
TI  - Modeling bulk and surface Pt using the "Gaussian and plane wave" density
      functional theory formalism: validation and comparison to k-point plane wave
      calculations.
AB  - We present a study on structural and electronic properties of bulk platinum and
      the two surfaces (111) and (100) comparing the Gaussian and plane wave method to
      standard plane wave schemes, normally employed for density functional theory
      calculations on metallic systems. The aim of this investigation is the assessment
      of methods based on the expansion of the Kohn-Sham orbitals into localized basis
      sets and on the supercell approach, in the description of the metallicity of Pt.
      Electronic structure calculations performed at Gamma-point only on supercells of
      different sizes, from 108 up to 864 atoms, are compared to the results obtained
      for the unit cell of four Pt atoms where the k-point expansion of the wave
      function over Monkhorst-Pack grids up to (10x10x10) has been employed. The
      evaluation of the two approaches with respect to bulk properties is done through
      the calculation of the equilibrium lattice constant, the bulk modulus, and the
      total and the d-projected density of states. For the Pt(111) and Pt(100)
      surfaces, we consider the relaxation of the first layers, the surface energies,
      the work function, the total density of states, as well as the center and filling
      of the d bands. Our results confirm that the accuracy of two approaches in the
      description of electronic and structural properties of Pt is equivalent,
      providing that consistent supercells and k-point meshes are used. Moreover, we
      estimate the supercell size that can be safely adopted in the Gaussian and plane
      wave method in order to obtain the same reliability of previous theoretical
      studies based on well converged plane wave calculations available in literature.
      The latter studies, in turn, set the level of agreement with experimental data.
      In particular, we obtain excellent agreement in the evaluation of the density of
      states for either bulk and surface systems, and our data are also in good
      agreement with previous works on Pt reported in literature. We conclude that
      Gaussian and plane wave calculations, with simulation cells of 400-800 atoms, can
      be safely used in the study of chemistry related problems involving transition
      metal surfaces.

PMID- 19102549
TI  - Gas-liquid nucleation in a two dimensional system.
AB  - We study the nucleation of liquid phase from a supersaturated vapor in two
      dimensions, where the particles interact through Lennard-Jones (LJ) pairwise
      potential. Using different Monte Carlo simulation methods, we calculate the free
      energy barrier for nucleation, the line tension, and bulk densities of
      equilibrium liquid and vapor phases, and also investigate the size and shape of
      the critical nucleus. The study is carried out at an intermediate level of
      supersaturation (away from the spinodal limit). In two dimensions, a surprisingly
      large cutoff (r(c) > or = 7.0sigma, sigma is the diameter of LJ particles) in the
      truncation of the LJ potential is required to obtain converged results. A lower
      cutoff [typically 2.5sigma which is generally sufficient in three dimensional
      (3D) studies] leads to a substantial error in the values of the line tension,
      nucleation barrier, and characteristics of the critical cluster. It is found that
      in two dimensions, the classical nucleation theory (CNT) fails to provide a
      reliable estimate of the free energy barrier. It underestimates the barrier by as
      much as 50% at the saturation ratio S = 1.1 (defined as S = P/P(C), where P(C) is
      the coexistence pressure) and at the reduced temperature T(*) = 0.427 (defined as
      T(*) = k(B)T/epsilon, where epsilon is the depth of the potential well).
      Interestingly, CNT has been found to overestimate the nucleation free energy
      barrier in 3D systems near the triple point. In fact, the agreement of the
      calculated nucleation rate with CNT is much worse in two dimensions than in three
      dimensions. The reason for the inadequacy of the CNT can be attributed to the
      noncircular nature of the critical clusters. Although the shape becomes
      increasingly circular and the clusters become more compact with increase in
      cutoff radius, an appreciable noncircular nature remains even without any cutoff
      to make the simple CNT inaccurate.

PMID- 19102550
TI  - Thermodynamic and kinetic approach in density functional theory studies of
      microscopic structure of GaN(0001) surface in ammonia-rich conditions.
AB  - GaN (0001) surface in an ammonia-rich vapor ambient, typical for ammonia
      annealing, metalo-organic vapor phase epitaxy (MOVPE) or hydride vapor phase
      epitaxy (HVPE) was considered. It was shown that, in these three cases, the
      stationary state of the surface corresponds to condition far from equilibrium.
      The chemical potential of nitrogen and hydrogen at the surface was determined
      using kinetic arguments, i.e., derived form the magnitude of flux of ammonia. For
      HVPE and MOVPE growth, the chemical potential of gallium depends on the distance
      from the steps. Thus, only far distance from the step value of the gallium
      chemical potential at the GaN(0001) surface could be determined in similar way.
      In the alternative case of GaN annealing in ammonia atmosphere, gallium chemical
      potential at the surface remains undetermined (the surface is in a metastable
      state). Additionally, using thermodynamic arguments, the limits for the chemical
      potential of gallium (upper) and nitrogen (lower) were formulated for the case of
      vapor growth, and expressed as functions of temperature and pressure. The
      results, regarding the atomic processes on the GaN(0001) surface, were obtained
      using the SIESTA, density functional theory based code, and consequently employed
      in the comparable thermodynamic and kinetic analysis of the state of GaN(0001)
      surface.

PMID- 19102551
TI  - On the origin of the electrostatic potential difference at a liquid-vacuum
      interface.
AB  - The microscopic origin of the interface potential calculated from computer
      simulations is elucidated by considering a simple model of molecules near an
      interface. The model posits that molecules are isotropically oriented and their
      charge density is Gaussian distributed. Molecules that have a charge density that
      is more negative toward their interior tend to give rise to a negative interface
      potential relative to the gaseous phase, while charge densities more positive
      toward their interior give rise to a positive interface potential. The interface
      potential for the model is compared to the interface potential computed from
      molecular dynamics simulations of the nonpolar vacuum-methane system and the
      polar vacuum-water interface system. The computed vacuum-methane interface
      potential from a molecular dynamics simulation (-220 mV) is captured with
      quantitative precision by the model. For the vacuum-water interface system, the
      model predicts a potential of -400 mV compared to -510 mV, calculated from a
      molecular dynamics simulation. The physical implications of this isotropic
      contribution to the interface potential is examined using the example of ion
      solvation in liquid methane.

PMID- 19102552
TI  - Tunable surface band gap in Mg(x)Zn(1-x)O thin films.
AB  - Mg(x)Zn(1-x)O thin films epitaxially grown on Mo(110) substrate under ultrahigh
      vacuum condition were studied in situ by various surface analysis techniques
      including x-ray photoelectron spectroscopy, Auger electron spectroscopy, low
      energy electron diffraction, and high resolution electron energy loss
      spectroscopy. The results indicate that as-grown Mg(x)Zn(1-x)O films are soluble
      phase, and a phase transition from wurtzite to cubic structure occurs in the
      region of x = 0.55-0.67. The surface band gap can be tuned continuously with
      altering the content of Mg in Mg(x)Zn(1-x)O films, and its tunable window width
      is about 1.9 eV. Based on heterojunction and quantum well structure, this kind of
      materials can be applied in wide-band-gap semiconductor devices, such as short
      wavelength light-emitting devices.

PMID- 19102553
TI  - Spin-current rectification in an organic magnetic/nonmagnetic device.
AB  - We propose a spin diode based on an organic magnetic co-oligomer or a
      magnetic/nonmagnetic heterojunction structure. The current and its spin
      polarization in the device are calculated with the spin-dependent Landauer
      Buttiker formula. It is found that, by reversing the applied bias, the charge
      current and the spin current (SC) may be rectified at the same time or
      separately. A normal charge-current rectification usually takes place if the
      spatial electric structure is asymmetric. While a spin-current rectification may
      appear in two forms or their combination: one is that the spin-polarized
      orientation keeps unchanged but the magnitude of the SC is asymmetric with the
      bias; another is that only the spin orientation of the SC flips when the bias is
      reversed. By designing a suitable organic spin device, either of the two kinds of
      spin-current rectifications is obtained in our calculations. Finally, the effects
      of the properties of the organic interlayer and the structural asymmetry on the
      rectification are discussed.

PMID- 19102554
TI  - The growth of AA graphite on (111) diamond.
AB  - Stacked AA graphite has been synthesized using a high-density dc plasma in
      hydrogen-methane mixtures. Graphene layers have been grown epitaxially with 2-1
      registration between the AA graphitic edges and the (111) surface of diamond. In
      addition, a new graphite crystal structure containing AA(') graphene layers,
      where alternate planes are translated by half the hexagon width, is formed by 1-1
      registry. The resulting interplanar distances of the AA graphite at the interface
      range from 2.20 A for the 1-1 registration to 4.40 A for the 2-1 registration and
      have been measured directly by high-resolution transmission electron microscopy
      (TEM). The appearance of the characteristic d-spacings, 3.55, 2.15, 1.80, 1.75
      (not fully resolved), and 1.25 A in the selective area diffraction patterns from
      the TEM, are consistent with reflections from the (001), (100), (102), (002), and
      (110) planes of the AA graphite. Simulation of the diffraction patterns,
      employing the structural factors of graphene, confirms the existence of AA
      graphite.

PMID- 19102555
TI  - Fluorine diffusion assisted by diffusing silicon on the Si(111)-(7x7) surface.
AB  - The diffusion process of fluorine (F) atoms on the Si(111)-(7x7) surface is
      investigated using high-temperature scanning tunneling microscopy. The kinetic
      parameters of F hopping agree well with those of the diffusing silicon (Si)
      atoms, which implies that of all reaction processes, the Si diffusion serves as
      the rate-determining one. Deposition of Si on the surface is found to enhance F
      hopping, which supports the above-mentioned observation. Theory reveals that the
      replacement of F adsorption sites by diffusing Si atoms is the key process in the
      diffusion mechanism.

PMID- 19102556
TI  - Isolating excitonic Raman coherence in semiconductors using two-dimensional
      correlation spectroscopy.
AB  - We present the experimental and simulation results of two-dimensional optical
      coherent correlation spectroscopy signals along the phase-matching direction k(I)
      = -k(1) + k(2) + k(3) projected on the two-dimensional (2D) (Omega(3),Omega(2))
      plane corresponding to the second and third delay periods. Overlapping Raman
      coherences in the conventional (Omega(3),Omega(1)) 2D projection may now be
      clearly resolved. The linewidths of the heavy-hole (HH) and light-hole (LH)
      excitonic Raman coherence peaks are obtained. Further insights on the higher
      order (beyond time-dependent Hartree-Fock) correlation effects among mixed (HH
      and LH) two excitons can be gained by using a cocircular pulse polarization
      configuration.

PMID- 19102557
TI  - Charge-transport-mediated recruitment of DNA repair enzymes.
AB  - Damaged or mismatched bases in DNA can be repaired by base excision repair
      enzymes (BER) that replace the defective base. Although the detailed molecular
      structures of many BER enzymes are known, how they colocalize to lesions remains
      unclear. One hypothesis involves charge transport (CT) along DNA [Yavin et al.,
      Proc. Natl. Acad. Sci. U.S.A. 102, 3546 (2005)]. In this CT mechanism, electrons
      are released by recently adsorbed BER enzymes and travel along the DNA. The
      electrons can scatter (by heterogeneities along the DNA) back to the enzyme,
      destabilizing and knocking it off the DNA, or they can be absorbed by nearby
      lesions and guanine radicals. We develop a stochastic model to describe the
      electron dynamics and compute probabilities of electron capture by guanine
      radicals and repair enzymes. We also calculate first passage times of electron
      return and ensemble average these results over guanine radical distributions. Our
      statistical results provide the rules that enable us to perform implicit-electron
      Monte Carlo simulations of repair enzyme binding and redistribution near lesions.
      When lesions are electron absorbing, we show that the CT mechanism suppresses
      wasteful buildup of enzymes along intact portions of the DNA, maximizing enzyme
      concentration near lesions.

PMID- 19102558
TI  - Analytical and numerical studies of sequence dependence of passage times for
      translocation of heterobiopolymers through nanopores.
AB  - We consider chaperone-assisted translocation of biopolymers with two distinct
      monomers or bases A and B, with the size of the chaperones being lambda sigma,
      where sigma is a monomer's size. The probability that A and B are neighbors in
      the biopolymer is P(AB). A master equation is used, together with the detailed
      balanced condition, in order to derive analytical results for the statistics of
      the first-passage times of the biopolymer as a function of P(AB), lambda, and the
      biopolymer's configuration. Monte Carlo simulations have also been carried out in
      order to compute the same quantities for biopolymers with 100-900 monomers and
      several lambda. The results indicate nontrivial dependence of the variance of the
      translocation times on the biopolymer's composition. It is also shown that
      measurements of the first two moments of the biopolymer's first-passage time
      distribution provide information on its length and ordering. Moreover, the
      probability density function Q(t) of the first-passage times is almost Gaussian
      for small chaperone size lambda, but becomes non-Gaussian as lambda increases. At
      large times, Q(t) decays exponentially.

PMID- 19102559
TI  - Closed-form expressions of the chemical potential for integral equation closures
      with certain bridge functions.

PMID- 19102560
TI  - Elastic anisotropy of human cortical bone secondary osteons measured by
      nanoindentation.
AB  - The identification of anisotropic elastic properties of lamellar bone based on
      nanoindentation data is an open problem. Therefore, the purpose of this study was
      to develop a method to estimate the orthotropic elastic constants of human
      cortical bone secondary osteons using nanoindentation in two orthogonal
      directions. Since the indentation modulus depends on all elastic constants and,
      for anisotropic materials, also on the indentation direction, a theoretical model
      quantifying the indentation modulus from the stiffness tensor of a given material
      was implemented numerically (Swadener and Pharr, 2001, "Indentation of
      Elastically Anisotropic Half-Spaces by Cones and Parabolae of Revolution,"
      Philos. Mag. A, 81(2), pp. 447-466). Nanoindentation was performed on 22 osteons
      of the distal femoral shaft: A new holding system was designed in order to indent
      the same osteon in two orthogonal directions. To interpret the experimental
      results and identify orthotropic elastic constants, an inverse procedure was
      developed by using a fabric-based elastic model for lamellar bone. The
      experimental indentation moduli were found to vary with the indentation direction
      and showed a marked anisotropy. The estimated elastic constants showed different
      degrees of anisotropy among secondary osteons of the same bone and these degrees
      of anisotropy were also found to be different than the one of cortical bone at
      the macroscopic level. Using the log-Euclidean norm, the relative distance
      between the compliance tensors of the estimated mean osteon and of cortical bone
      at the macroscopic level was 9.69%: Secondary osteons appeared stiffer in their
      axial and circumferential material directions, and with a greater bulk modulus
      than cortical bone, which is attributed to the absence of vascular porosity in
      osteonal properties. The proposed method is suitable for identification of
      elastic constants from nanoindentation experiments and could be adapted to other
      (bio)materials, for which it is possible to describe elastic properties using a
      fabric-based model.

PMID- 19102561
TI  - Freezing-induced fluid-matrix interaction in poroelastic material.
AB  - Freezing of biological tissue is emerging in various biomedical applications. The
      success of these applications requires precise control of the tissue
      functionality, which is closely associated with the microstructure of the
      extracellular matrix (ECM). In the present study, the spatiotemporal effects of
      freezing on the ECM were experimentally and theoretically investigated by
      approximating biological tissue as a poroelastic material saturated with
      interstitial fluid. The experiments with type I collagen gel showed that its
      matrix underwent two distinct levels of structural changes due to freezing:
      enlarged pore structure of the matrix and increased collagen fibril diameters.
      The extent of these changes was augmented as the freezing temperature was
      lowered. The theoretical model suggested that the interstitial fluid might be
      transported toward the unfrozen region from the phase change interface due to the
      volumetric expansion associated with the water-ice phase change, and the
      transported fluid could interact with the matrix and enlarge its pore structure.
      The model also illustrated the effects of matrix structural properties on this
      interaction including initial porosity, hydraulic conductivity, and elastic
      modulus. These results imply that an identical macroscopic freezing protocol may
      result in different microstructural alterations of poroelastic materials
      depending on the structural properties of the matrix. This may be relevant to
      understanding the tissue-type dependent outcomes of cryomedicine applications and
      be useful in designing cryomedicine applications for a wide variety of tissues.

PMID- 19102562
TI  - Computational modeling of LDL and albumin transport in an in vivo CT image-based
      human right coronary artery.
AB  - Low wall shear stress (WSS) is implicated in endothelial dysfunction and
      atherogenesis. The accumulation of macromolecules is also considered as an
      important factor contributing to the development of atherosclerosis. In the
      present study, a fluid-wall single-layered model incorporated with shear
      dependent transport parameters was used to investigate albumin and low-density
      lipoprotein (LDL) transport in an in vivo computed tomographic image-based human
      right coronary artery (RCA). In the fluid-wall model, the bulk blood flow was
      modeled by the Navier-Stokes equations, Darcy's law was employed to model the
      transmural flow in the arterial wall, mass balance of albumin and LDL was
      governed by the convection-diffusion mechanism with an additional reaction term
      in the wall, and the Kedem-Katchalsky equations were applied at the endothelium
      as the interface condition between the lumen and wall. Shear-dependent models for
      hydraulic conductivity and albumin permeability were derived from experimental
      data in literature to investigate the influence of WSS on macromolecular
      accumulation in the arterial wall. A previously developed so-called lumen-free
      time-averaged scheme was used to approximate macromolecular transport under
      pulsatile flow conditions. LDL and albumin accumulations in the subendothelial
      layer were found to be colocalized with low WSS. Two distinct mechanisms
      responsible for the localized accumulation were identified: one was insufficient
      efflux from the subendothelial layer to outer wall layers caused by a weaker
      transmural flow; the other was excessive influx to the subendothelial layer from
      the lumen caused by a higher permeability of the endothelium. The comparison
      between steady flow and pulsatile flow results showed that the dynamic behavior
      of the pulsatile flow could induce a wider and more diffuse macromolecular
      accumulation pattern through the nonlinear shear-dependent transport properties.
      Therefore, it is vital to consider blood pulsatility when modeling the shear
      dependent macromolecular transport in large arteries. In the present study, LDL
      and albumin accumulations were observed in the low WSS regions of a human RCA
      using a fluid-wall mass transport model. It was also found that steady flow
      simulation could overestimate the magnitude and underestimate the area of
      accumulations. The association between low WSS and accumulation of macromolecules
      leading to atherosclerosis may be mediated through effects on transport
      properties and mass transport and is also influenced by flow pulsatility.

PMID- 19102563
TI  - Slow-time changes in human EMG muscle fatigue states are fully represented in
      movement kinematics.
AB  - The ability to identify physiologic fatigue and related changes in kinematics can
      provide an important tool for diagnosing fatigue-related injuries. This study
      examined an exhaustive cycling task to demonstrate how changes in movement
      kinematics and variability reflect underlying changes in local muscle states.
      Motion kinematics data were used to construct fatigue features. Their
      multivariate analysis, based on smooth orthogonal decomposition, was used to
      reconstruct physiological fatigue. Two different features composed of (1)
      standard statistical metrics (SSM), which were a collection of standard long-time
      measures, and (2) phase space warping (PSW)-based metrics, which characterized
      short-time variations in the phase space trajectories, were considered. Movement
      kinematics and surface electromyography (EMG) signals were measured from the
      lower extremities of seven highly trained cyclists as they cycled to voluntary
      exhaustion on a stationary bicycle. Mean and median frequencies from the EMG time
      series were computed to measure the local fatigue dynamics of individual muscles
      independent of the SSM- and PSW-based features, which were extracted solely from
      the kinematics data. A nonlinear analysis of kinematic features was shown to be
      essential for capturing full multidimensional fatigue dynamics. A four
      dimensional fatigue manifold identified using a nonlinear PSW-based analysis of
      kinematics data was shown to adequately predict all EMG-based individual muscle
      fatigue trends. While SSM-based analyses showed similar dominant global fatigue
      trends, they failed to capture individual muscle activities in a low-dimensional
      manifold. Therefore, the nonlinear PSW-based analysis of strictly kinematic time
      series data directly predicted all of the local muscle fatigue trends in a low
      dimensional systemic fatigue trajectory. These results provide the first direct
      quantitative link between changes in muscle fatigue dynamics and resulting
      changes in movement kinematics.

PMID- 19102564
TI  - Defining the flexion-extension axis of the ulna: implications for intra-operative
      elbow alignment.
AB  - The increased utilization of total elbow replacements has resulted in a
      correspondingly increased number of failed implants requiring revision. The most
      common reason for revision is aseptic loosening of the ulnar component due to
      polyethylene induced osteolysis. Implant malalignment is thought to be an
      important cause of bearing wear and implant failure. The ulnar flexion axis can
      be used to accurately align the ulnar component of the elbow implant; however,
      the optimal method of determining this axis intra-operatively is unknown. This in
      vitro study determined the relationship amongst kinematically and anatomically
      defined ulnar flexion axes in an effort to improve the accuracy of ulnar
      component positioning. Five different techniques were used to determine the ulnar
      flexion axis in 12 cadaveric specimens, 3 kinematic and 2 anatomic. The
      techniques were compared with the screw displacement axis from simulated elbow
      flexion. An anatomic measurement technique using the guiding ridge of the greater
      sigmoid notch of the ulna and the radial head was found to most accurately
      replicate the position and orientation of the screw displacement axis of the
      elbow (p<0.05). Because an anatomically derived flexion axis can be determined
      using both pre-operative imaging techniques, as well as with intra-operative
      guides, it is more practical than kinematically derived techniques requiring
      tracking systems for clinical application and should provide reliable and
      consistent results.

PMID- 19102565
TI  - Cytoskeleton-membrane interactions in neuronal growth cones: a finite analysis
      study.
AB  - Revealing the molecular events of neuronal growth is critical to obtaining a
      deeper understanding of nervous system development, neural injury response, and
      neural tissue engineering. Central to this is the need to understand the
      mechanical interactions between the cytoskeleton and the cell membrane, and how
      these interactions affect the overall growth mechanics of neurons. Using finite
      element analysis, the stress in the membrane produced by an actin filament or a
      microtubule acting against a deformable membrane was modeled, and the
      deformation, stress, and strain were computed for the membrane. Parameters to
      represent the flexural rigidities of the well-studied actin and tubulin
      cytoskeletal proteins, as well as the mechanical properties of cell membranes,
      were used in the simulations. Our model predicts that a single actin filament is
      able to produce a normal contact stress on the cell membrane that is sufficient
      to cause membrane deformation but not growth. Our model also predicts that under
      clamped boundary conditions a filament with a buckling strength equal to or
      smaller than an actin filament would not cause the areal strain in the membrane
      to exceed 3%, and therefore the filament is incapable of causing membrane rupture
      or puncture to a safety factor of approximately 15-25. Decreasing the radius of
      the membrane upon which the normal contact stress is acting allows an increase in
      the amount of normal contact stress that the membrane can withstand before
      rupture. The model predicts that a 50 nm radius membrane can withstand
      approximately 4 MPa of normal contact stress before membrane rupture whereas a
      250 nm radius membrane can withstand approximately 2.5 MPa. Understanding how the
      mechanical properties of cytoskeletal elements have coevolved with their
      respective cell membranes may yield insights into the events that gave rise to
      the sequences and superquaternary structures of the major cytoskeletal proteins.
      Additionally, numerical modeling of membranes can be used to analyze the forces
      and stresses generated by nanoscale biological probes during cellular injection.

PMID- 19102566
TI  - An adjustable triple-bifurcation unit model for air-particle flow simulations in
      human tracheobronchial airways.
AB  - A new methodology for a swift and accurate computer simulation of large segments
      of the human lung airways is presented. Focusing on a representative
      tracheobronchial (TB) region, i.e., G0-G15, nano- and micron particle transports
      have been simulated for Q(in)=30 lmin, employing an experimentally validated
      computer model. The TB tree was geometrically decomposed into triple-bifurcation
      units with kinematically adjusted multilevel outlet/inlet conditions. Deposition
      patterns and maximum concentrations differ greatly between nanoparticles (1< or
      =d(p)< or =150 nm) and micron particles (1< or =d(p)< or =10 microm), which may
      relate uniquely to health impacts. In comparison with semi-analytical particle
      deposition results, it is shown that such simple "lung models" cannot predict
      local deposition values but can match computer simulation results for the entire
      TB region within 2.5-26%. The present study revealed that turbulent air-particle
      flow may propagate to G5 for the assumed inhalation flow rate. Geometry and
      upstream effects are more pronounced for micron particle deposition than for
      nanoparticle deposition.

PMID- 19102567
TI  - A coaxial tube model of the cerebrospinal fluid pulse propagation in the spinal
      column.
AB  - The dynamics of the movement of the cerebrospinal fluid (CSF) may play an
      important role in the genesis of pathological neurological conditions such as
      syringomyelia, which is characterized by the presence of a cyst (syrinx) in the
      spinal cord. In order to provide sound theoretical grounds for the hypotheses
      that attribute the formation and growth of the syrinx to impediments to the
      normal movement of the CSF, it is necessary to understand various modes through
      which CSF pulse in the spinal column propagates. Analytical models of small
      amplitude wave propagation in fluid-filled coaxial tubes, where the outer tube
      represents dura, the inner tube represents the spinal cord, and the fluid is the
      CSF, have been used to that end. However, so far, the tendency was to model one
      of the two tubes as rigid and to neglect the effect of finite thickness of the
      tube walls. The aim of this study is to extend the analysis in order to address
      these two potentially important issues. To that end, classical linear small
      amplitude analysis of wave propagation was applied to a system consisting of
      coaxial tubes of finite thickness filled with inviscid incompressible fluid.
      General solutions to the governing equations for the case of harmonic waves in
      the long wave limit were replaced with the boundary conditions to yield the
      characteristic (dispersion) equation for the system. The four roots of the
      characteristic equation correspond to four modes of wave propagation, of which
      the first three are associated with significant motion of the CSF. For the normal
      range of parameters the speeds of the four modes are c(1)=13 ms, c(2)=14.7 ms,
      c(3)=30.3 ms, and c(4)=124.5 ms, which are well within the range of values
      previously reported in experimental and theoretical studies. The modes with the
      highest and the lowest speeds of propagation can be attributed to the dura and
      the spinal cord, respectively, whereas the remaining two modes involve some
      degree of coupling between the two. When the thickness of the spinal cord, is
      reduced below its normal value, the first mode becomes dominant in terms of the
      movement of the CSF, and its speed drops significantly. This suggests that the
      syrinx may be characterized by an abnormally low speed of the CSF pulse.

PMID- 19102568
TI  - Invariant-based anisotropic constitutive models of the healthy and aneurysmal
      abdominal aortic wall.
AB  - The arterial wall is a complex fiber-reinforced composite. Pathological
      conditions, such as aneurysms, significantly alter the mechanical response of the
      arterial wall, resulting in a loss of elasticity, enhanced anisotropy, and
      increased chances of mechanical failure. Invariant-based models of the healthy
      and aneurysmal abdominal aorta were constructed based on first principles and
      published experimental data with implementations for several numerical cases, as
      well as comparisons to current healthy and aneurysmal tissue data. Inherent
      limitations of a traditional invariant-based methodology are also discussed and
      compared to the models' ability to accurately reproduce experimental trends. The
      models capture the nonlinear and anisotropic mechanical responses of the two
      arterial sections and make reasonable predictions regarding the effects of
      alterations in healthy and diseased tissue histology. Additionally, the new
      models exhibit convex and anisotropic monotonically increasing energy contours
      (suggesting numerical stability) but have potentially the inherent limitations of
      a covariant theoretical framework. Although the traditional invariant framework
      exhibits significant covariance, the invariant terms utilized in the new models
      exhibited limited covariance and are able to accurately reproduce experimental
      trends. A streamlined implementation is also possible for future numerical
      investigations of fluid-structure interactions in abdominal aortic aneurysms.

PMID- 19102569
TI  - Three-dimensional computational modeling of subject-specific cerebrospinal fluid
      flow in the subarachnoid space.
AB  - This study aims at investigating three-dimensional subject-specific cerebrospinal
      fluid (CSF) dynamics in the inferior cranial space, the superior spinal
      subarachnoid space (SAS), and the fourth cerebral ventricle using a combination
      of a finite-volume computational fluid dynamics (CFD) approach and magnetic
      resonance imaging (MRI) experiments. An anatomically accurate 3D model of the
      entire SAS of a healthy volunteer was reconstructed from high resolution T2
      weighted MRI data. Subject-specific pulsatile velocity boundary conditions were
      imposed at planes in the pontine cistern, cerebellomedullary cistern, and in the
      spinal subarachnoid space. Velocimetric MRI was used to measure the velocity
      field at these boundaries. A constant pressure boundary condition was imposed at
      the interface between the aqueduct of Sylvius and the fourth ventricle. The
      morphology of the SAS with its complex trabecula structures was taken into
      account through a novel porous media model with anisotropic permeability. The
      governing equations were solved using finite-volume CFD. We observed a total
      pressure variation from -42 Pa to 40 Pa within one cardiac cycle in the
      investigated domain. Maximum CSF velocities of about 15 cms occurred in the
      inferior section of the aqueduct, 14 cms in the left foramen of Luschka, and 9
      cms in the foramen of Magendie. Flow velocities in the right foramen of Luschka
      were found to be significantly lower than in the left, indicating three
      dimensional brain asymmetries. The flow in the cerebellomedullary cistern was
      found to be relatively diffusive with a peak Reynolds number (Re)=72, while the
      flow in the pontine cistern was primarily convective with a peak Re=386. The net
      volumetric flow rate in the spinal canal was found to be negligible despite CSF
      oscillation with substantial amplitude with a maximum volumetric flow rate of 109
      mlmin. The observed transient flow patterns indicate a compliant behavior of the
      cranial subarachnoid space. Still, the estimated deformations were small owing to
      the large parenchymal surface. We have integrated anatomic and velocimetric MRI
      data with computational fluid dynamics incorporating the porous SAS morphology
      for the subject-specific reconstruction of cerebrospinal fluid flow in the
      subarachnoid space. This model can be used as a basis for the development of
      computational tools, e.g., for the optimization of intrathecal drug delivery and
      computer-aided evaluation of cerebral pathologies such as syrinx development in
      syringomelia.

PMID- 19102570
TI  - Load transfer mechanism for different metatarsal geometries: a finite element
      study.
AB  - The load transfer mechanism across the skeleton of the human foot is very
      important to understand its biomechanical function. In this work, we develop
      several computational models to compare the biomechanical response of different
      metatarsal geometries. Finite element 3D simulations of feet reconstructed from
      computer tomography (CT) scans were used to evaluate the stress/strain
      distributions during the stance posture. The numerical predictions for
      pathological and healthy foot geometries present different load transfer
      mechanisms that can provide a biomechanical explanation of why some metatarsal
      geometrical configurations cause different foot skeletal stresses. The most
      significant result in all cases was a reduction between 20% and 30% of the peak
      load supported by the first metatarsal. Therefore, we conclude that a clearly
      unloaded first metatarsal, overloading the rest, is a risk factor to induce
      metatarsalgia.

PMID- 19102571
TI  - Assessment by finite element modeling indicates that surgical intramuscular
      aponeurotomy performed closer to the tendon enhances intended acute effects in
      extramuscularly connected muscle.
AB  - The effects of location of aponeurotomy on the muscular mechanics of
      extramuscularly connected muscle were assessed. Using finite element modeling,
      extensor digitorum longus muscle of the rat was studied for the effects of
      aponeurotomy performed in each of three locations on the proximal aponeurosis:
      (1) a proximal location (case P), (2) an intermediate location (case I), and (3)
      a distal location (case D). Proximo-distal force differences were more pronounced
      for more proximal aponeurotomy. The location also affected proximally and
      distally assessed muscle length-force characteristics: (1) Muscle optimum length
      and active slack length shifted differentially to higher lengths, increasing
      slack to optimum length range (for D to P: distally by 15-44%; proximally by 2
      6%). (2) Muscle forces decreased at all lengths (e.g., for D to P distal optimal
      force=88-68% and proximal optimal force=87-60% of intact values, respectively).
      Increased length range and force decreases were highest for case P, as were
      effects on muscle geometry: gap length within the proximal aponeurosis; decreased
      proximal fiber population pennation angle. Parallel, but not serial,
      heterogeneity of sarcomere length was highest in case P: (a) For the distal fiber
      population, sarcomere shortening was highest; (b) for the proximal population,
      sarcomeres were longer. It is concluded that if aponeurotomy is performed closer
      to the tendon, intended surgical effects are more pronounced. For bi-articular
      muscle, mechanics of both proximal and distal joints will be affected, which
      should be considered in selecting the location of aponeurotomy for optimal
      results at both joints.

PMID- 19102572
TI  - Choice of in vivo versus idealized velocity boundary conditions influences
      physiologically relevant flow patterns in a subject-specific simulation of flow
      in the human carotid bifurcation.
AB  - Accurate fluid mechanics models are important tools for predicting the flow field
      in the carotid artery bifurcation and for understanding the relationship between
      hemodynamics and the initiation and progression of atherosclerosis. Clinical
      imaging modalities can be used to obtain geometry and blood flow data for
      developing subject-specific human carotid artery bifurcation models. We developed
      subject-specific computational fluid dynamics models of the human carotid
      bifurcation from magnetic resonance (MR) geometry data and phase contrast MR
      velocity data measured in vivo. Two simulations were conducted with identical
      geometry, flow rates, and fluid parameters: (1) Simulation 1 used in vivo
      measured velocity distributions as time-varying boundary conditions and (2)
      Simulation 2 used idealized fully-developed velocity profiles as boundary
      conditions. The position and extent of negative axial velocity regions (NAVRs)
      vary between the two simulations at any given point in time, and these regions
      vary temporally within each simulation. The combination of inlet velocity
      boundary conditions, geometry, and flow waveforms influences NAVRs. In
      particular, the combination of flow division and the location of the velocity
      peak with respect to individual carotid geometry landmarks (bifurcation apex
      position and the departure angle of the internal carotid) influences the size and
      location of these reversed flow zones. Average axial wall shear stress (WSS)
      distributions are qualitatively similar for the two simulations; however,
      instantaneous WSS values vary with the choice of velocity boundary conditions. By
      developing subject-specific simulations from in vivo measured geometry and flow
      data and varying the velocity boundary conditions in otherwise identical models,
      we isolated the effects of measured versus idealized velocity distributions on
      blood flow patterns. Choice of velocity distributions at boundary conditions is
      shown to influence pathophysiologically relevant flow patterns in the human
      carotid bifurcation. Although mean WSS distributions are qualitatively similar
      for measured and idealized inlet boundary conditions, instantaneous NAVRs differ
      and warrant imposing in vivo velocity boundary conditions in computational
      simulations. A simulation based on in vivo measured velocity distributions is
      preferred for modeling hemodynamics in subject-specific carotid artery
      bifurcation models when studying atherosclerosis initiation and development.

PMID- 19102573
TI  - A nonintrusive method of measuring the local mechanical properties of soft
      hydrogels using magnetic microneedles.
AB  - Soft hydrogels serving as substrates for cell attachment are used to culture many
      types of cells. The mechanical properties of these gels influence cell
      morphology, growth, and differentiation. For studies of cell growth on
      inhomogeneous gels, techniques by which the mechanical properties of the
      substrate can be measured within the proximity of a given cell are of interest.
      We describe an apparatus that allows the determination of local gel elasticity by
      measuring the response of embedded micron-sized magnetic needles to applied
      magnetic fields. This microscope-based four-magnet apparatus can apply both force
      and torque on the microneedles. The force and the torque are manipulated by
      changing the values of the magnetic field at the four poles of the magnet using a
      feedback circuit driven by LABVIEW. Using Hall probes, we have mapped out the
      magnetic field and field gradients produced by each pole when all the other poles
      are held at zero magnetic field. We have verified that superposition of these
      field maps allows one to obtain field maps for the case when the poles are held
      at arbitrary field values. This allows one to apply known fields and field
      gradients to a given microneedle. An imaging system is employed to measure the
      displacement and rotation of the needles. Polyacrylamide hydrogels of known
      elasticity were used to determine the relationship between the field gradient at
      the location of the needles and the force acting on the needles. This
      relationship allows the force on the microneedle to be determined from a known
      field gradient. This together with a measurement of the displacement of the
      needle in a given gel allows one to determine the stiffness (Fdelta) of the gel
      and the elastic modulus, provided Poison's ratio is known. Using this method, the
      stiffness and the modulus of elasticity of type-I collagen gels were found to be
      2.64+/-0.05 nNmicrom and 284.6+/-5.9 Pa, respectively. This apparatus is
      presently being employed to track the mechanical stiffness of the DNA-cross
      linked hydrogels, developed by our group, whose mechanical properties can be
      varied on demand by adding or removing cross-linker strands. Thus a system that
      can be utilized to track the local properties of soft media as a function of time
      with minimum mechanical disturbance in the presence of cells is presented.

PMID- 19102574
TI  - Comparison of kinematics, kinetics, and EMG throughout wheelchair propulsion in
      able-bodied and persons with paraplegia: an integrative approach.
AB  - A systematic integrated data collection and analysis of kinematic, kinetic, and
      electromyography (EMG) data allow for the comparison of differences in wheelchair
      propulsion between able-bodied individuals and persons with paraplegia. Kinematic
      data from a motion analysis system, kinetic data from force-sensing push rims,
      and electromyography data from four upper-limb muscles were collected for ten
      push strokes. Results are as follows: Individuals with paraplegia use a greater
      percentage of their posterior deltoids, biceps, and triceps in relation to
      maximal voluntary contraction. These persons also reached peak anterior deltoid
      firing nearly 10 deg earlier on the push rim, while reaching peak posterior
      deltoid nearly 10 deg later on the push rim. Able-bodied individuals had no
      triceps activity in the initial stages of propulsion while their paraplegic
      groups had activity throughout. Able-bodied participants also had, on average,
      peak resultant, tangential, and radial forces occurring later on the push rim (in
      degrees). There are two main conclusions that can be drawn from this integrative
      investigation: (1) A greater "muscle energy," as measured by the area under the
      curve of the percentage of EMG throughout propulsion, results in a greater
      resultant joint force in the shoulder and elbow, thus potentially resulting in
      shoulder pathology. (2) Similarly, a greater muscle energy may result in fatigue
      and play a factor in the development of shoulder pain and pathology over time;
      fatigue may compromise an effective propulsive stroke placing undue stresses on
      the joint capsule. Muscle activity differences may be responsible for the
      observed kinematic and kinetic differences between the two groups. The high
      incidence of shoulder pain in manual wheelchair users as compared to the general
      population may be the result of such differences, although the results from this
      biomedical investigation should be examined with caution. Future research into
      joint forces may shed light on this. Further investigation needs to focus on
      whether the pattern of kinematics, kinetics, and muscle activity during
      wheelchair propulsion is compensatory or evolutionary by tracking individuals
      longitudinally.

PMID- 19102575
TI  - Statistical analysis of interfacial gap in a cementless stem FE model.
AB  - In cementless total hip arthroplasty, a fair amount of interfacial gap exists
      between the femoral stem and the bone. However, the effect of these gaps on the
      mechanical stability of the stem is poorly understood. In this paper, a finite
      element model with various interfacial gap definitions is used to quantify the
      effect of interfacial gaps on the primary stability of a Versys Fiber Metal Taper
      stem under stair climbing loads. In the first part, 500 random interfacial gap
      definitions were simulated. The resulting micromotion was approximately inversely
      proportional to the contact ratio, and the variance of the micromotion was
      greater with a lower contact ratio. Moreover, when the magnitude of the
      micromotion was compared between the gap definitions that had contact at a
      specific site and those that had no contact at that site, it was found that gaps
      located in the proximal-medial region of the stem surface had the most important
      effect on the micromotion. In a second trial, 17 gap definitions mimicking a gap
      pattern that has been observed experimentally were simulated. For a given contact
      ratio, the micromotion observed in the second trial was lower than the average
      result of those in the first, where the gaps were placed randomly. In either
      trial, when the contact ratio was higher than 40%, the micromotion showed no
      significant difference (first trial) or a gentle slope (-0.24 mum% in the second
      trial) in relation to the contact ratio. Considering the reported contact ratios
      for properly implanted stems, variations in the amount of interfacial gap would
      not likely cause a drastic difference in micromotion, and this effect could be
      easily overshadowed by other clinical factors. In conclusion, differences in
      interfacial gaps are not expected to have a noticeable effect on the clinical
      micromotion of this cementless stem.

PMID- 19102576
TI  - The effect of screw pullout rate on screw purchase in synthetic cancellous bone.
AB  - Clinically, orthopaedic fracture fixation constructs are mounted using screws
      inserted into cancellous bone, while biomechanical studies are increasingly using
      commercially available synthetic bones. The goal of this study was to examine the
      effect of screw pullout rate on cancellous bone screw purchase strength in
      synthetic cancellous bone. Sixty synthetic cancellous bone cubes (40x40x40 mm(3))
      each had one orthopaedic cancellous bone screw (major diameter=6.5 mm) inserted
      to a depth of 30 mm. Screws were extracted to obtain outcome measures of failure
      force, failure shear stress, failure energy, failure displacement, resistance
      force, and removal energy. The ten test groups (n=6 cubes per group) had screws
      extracted at pullout rates of 1 mmmin, 2.5 mmmin, 5 mmmin, 7.5 mmmin, 10 mmmin,
      20 mmmin, 30 mmmin, 40 mmmin, 50 mmmin, and 60 mmmin. The aggregate average
      results for failure force, failure stress, failure energy, failure displacement,
      resistance force, and postfailure removal energy for combined pullout rates were,
      respectively, 984.8+/-63.9 N, 3.5+/-0.2 MPa, 298.3+/-41.7 J, 0.53+/-0.08 mm,
      453.8+/-19.6 N, and 5420.1+/-489.7 J. Most statistical differences (40 of 47)
      involved either the 5 mmmin or the 60 mmmin rates being compared to other rates.
      Failure force, failure stress, and resistance force increased and were highly
      linearly correlated with pullout rate (R(2)=0.78, 0.76, and 0.74, respectively).
      Failure energy, failure displacement, and removal energy were relatively
      unchanged over the pullout range tested, yielding low correlation coefficients
      (R(2)<0.05). Failure force, failure stress, and resistance force were affected by
      bone screw pullout rate in synthetic cancellous bone, while failure energy,
      failure displacement, and removal energy remained unchanged. This is the first
      study to perform an extensive investigation of cancellous bone screw pullout rate
      in synthetic cancellous bone.

PMID- 19102578
TI  - Mercury-induced reproductive impairment in fish.
AB  - Mercury is a potent neurotoxin, and increasing levels have led to concern for
      human and wildlife health in many regions of the world. During the past three
      decades, studies in fish have examined the effects of sublethal mercury exposure
      on a range of endpoints within the reproductive axis. Mercury studies have varied
      from highly concentrated aqueous exposures to ecologically relevant dietary
      exposures using levels comparable to those currently found in the environment.
      This review summarizes data from both laboratory and field studies supporting the
      hypothesis that mercury in the aquatic environment impacts the reproductive
      health of fish. The evidence presented suggests that the inhibitory effects of
      mercury on reproduction occur at multiple sites within the reproductive axis,
      including the hypothalamus, pituitary, and gonads. Accumulation of mercury in the
      fish brain has resulted in reduced neurosecretory material, hypothalamic neuron
      degeneration, and alterations in parameters of monoaminergic neurotransmission.
      At the level of the pituitary, mercury exposure has reduced and/or inactivated
      gonadotropin-secreting cells. Finally, studies have examined the effects of
      mercury on the reproductive organs and demonstrated a range of effects, including
      reductions in gonad size, circulating reproductive steroids, gamete production,
      and spawning success. Despite some variation between studies, there appears to be
      sufficient evidence from laboratory studies to link exposure to mercury with
      reproductive impairment in many fish species. Currently, the mechanisms
      underlying these effects are unknown; however, several physiological and cellular
      mechanisms are proposed within this review.

PMID- 19102579
TI  - Polybrominated diphenyl ether flame retardants in Chesapeake Bay region, U.S.A.,
      peregrine falcon (Falco peregrinus) eggs: urban/rural trends.
AB  - A total of 23 peregrine falcon (Falco peregrinus) eggs were obtained between 1993
      and 2002 from 13 nests, encompassing 11 locations in the Chesapeake Bay region,
      U.S.A. When multiple eggs were available from the same clutch, average clutch
      contaminant concentrations were calculated. An overall median total
      polybrominated diphenyl ether (PBDE) level of 201 ng/g wet weight was determined
      for the eggs/clutches examined. The maximum in an individual egg, from an urban
      highway bridge site, was 354 ng/g. This egg also exhibited the highest BDE 209
      burden (48.2 ng/g). Compared to distributions reported in fish and piscivorous
      birds, falcon eggs were enriched in the more brominated congeners. The BDE
      congeners 153, 99, and 100 constituted 26.0, 24.8, and 13.1%, respectively, of
      total PBDEs. In most aquatic species, BDE 47 is the most abundant congener
      reported; however, it constituted only 4.4% of total PBDEs in the eggs of the
      present study. The median BDE 209 concentration was 6.3 ng/g. The sum of the octa
      to nonabrominated congeners (BDEs 196, 197, 206, 207, and 208) contributed, on
      average, 14.0% of total PBDEs, exceeding the contribution of BDE 209 (5.9%).
      Concentrations of polychlorinated biphenyls (PCBs) and 1,1-dichloro-2,2-bis(p
      chlorophenyl)ethylene (4,4'-DDE) also were determined in a subset of 16 eggs
      (collected in 2001-2002 from six nests) and were an order of magnitude greater
      than the corresponding PBDEs. Median BDE 209 concentrations were significantly
      correlated (p < 0.01, Spearman R = 0.690) with the human population density of
      the area surrounding the nest. Total PBDEs, total PCBs, and 4,4'-DDE levels were
      not correlated to human population density.

PMID- 19102580
TI  - Toxic effects of oral hexahydro-1,3,5-trinitro-1,3,5-triazine in the western
      fence lizard (Sceloporus occidentalis).
AB  - Hexahydro-1,3,5-trinitro-1,3,5-triazine (RDX) has been widely used as an
      explosive in munition formulations, resulting in contamination of wildlife
      habitat on military installations. To estimate health effects for reptilian
      species, acute, subacute, and subchronic oral toxicity studies were conducted
      using the Western fence lizard (Sceloporus occidentalis). Estimated oral median
      lethal doses were 72 (95% confidence interval [CI], 49-106) mg/kg body weight
      (slope, 3.754) for males and 88 (95% CI, 65-119) mg/kg (slope, 4.525) for
      females. Toxicity from RDX suggested the neurological system as the critical
      target tissue. A 14-d subacute study followed with males dosed orally with RDX
      (corn oil) at 0, 10, 20, 25, 30, 45, and 60 mg/kg/d. Signs of toxicity frequently
      included a characteristic body posture. A significant dose-survival relationship
      was seen over the range of doses, with a significant decrease in survival at 20
      mg/kg/d. Males in the 60-d subchronic study were dosed at 0, 1, 2.5, 5, 8, and 11
      mg/kg/d, and signs of toxicity included lethargy, cachexia, and anorexia.
      Survival was decreased at 8 and 11 mg/kg/d. Reduced growth rate and food
      consumption occurred at 5 mg/kg/d. Brain tissue was assayed for RDX when seizures
      were observed at a residue concentration of at least 18 microg/g. No
      abnormalities were observed in the hematologic indices, whereas plasma proteins
      were reduced. Hepatic enlargement and decreased testes mass occurred at 8 and 11
      mg/kg/d. Plasma testosterone concentrations, sperm counts, and motility measures
      were variable for all treatment levels. Based on survival, growth rate, food
      intake, and testes to brain weight ratios, these data suggest a lowest-observed
      adverse effect level of 5 mg/kg/d and a no-observed-adverse effect level of 2.5
      mg/kg/d.

PMID- 19102581
TI  - Investigating aggregation in Suwannee River, U.S.A., dissolved organic matter
      using diffusion-ordered nuclear magnetic resonance spectroscopy.
AB  - Aggregation of the Suwannee River (USA) dissolved organic matter (SRDOM) is
      studied using nuclear magnetic resonance spectroscopy. Diffusion-ordered
      spectroscopy identifies two distinct bands, one corresponding to smaller
      components and the other to larger components. At lower concentrations (500 ppm),
      the dissolved organic matter (DOM) is present mainly as small components;
      however, with increasing concentration, the larger components become more
      pronounced as a result of aggregation. Calibrations indicate the small materials
      behave in a manner similar to that of maltodextrins of approximately 180 to 950
      Da or proteins of 100 to 1000 Da. The aggregated species show behavior similar to
      that of maltodextrins of approximately 1000 to 21,000 Da or proteins of 1050 to
      70,000 Da. The mean diffusivity of the aggregated components in SRDOM is
      consistent with that of maltodextrins of approximately 4500 Da and proteins of
      approximately 8000 Da at the highest concentration measured. At the lowest
      concentration (closest to environmental concentrations), little to no aggregation
      is observed. Diffusion profiles show an increase in large-molecular-weight
      material, with a simultaneous decrease in small-molecular-weight components with
      increasing DOM concentration. This suggests aggregates in SRDOM may be weak
      dispersive associations of low-molecular-weight material. Additionally, with a
      decrease in temperature, aggregates show faster diffusion, suggesting a tighter,
      more condensed arrangement. Further evidence supports DOM aggregation as
      conglomerations of numerous components in DOM rather than a more organized self
      association. Carboxyl-rich alicyclic molecules (CRAM) play a prominent role in
      aggregation of SRDOM and, to a lesser extent, material-derived from linear
      terpenoids (MDLT). The role of lignin and carbohydrates is less clear, although
      at least some of the lignin is present as macromolecules and tends to show
      interactions with both the MDLT and CRAM components.

PMID- 19102583
TI  - Levels and temporal trends (1983-2003) of polybrominated diphenyl ethers and
      hexabromocyclododecanes in seabird eggs from north Norway.
AB  - The present study assessed temporal trends (1983-2003) of polybrominated diphenyl
      ethers (PBDEs) and hexabromocyclododecanes (HBCDs) in eggs of herring gulls
      (Larus argentatus), Atlantic puffins (Fratercula arctica), and black-legged
      kittiwakes (Rissa tridactyla) in North Norway. Generally, PBDE concentrations
      increased between 1983 and 1993 and then leveled out, although species-specific
      trends were reported. Levels of alpha-HBCD increased in all species throughout
      the 20-year period. Levels of nona-BDEs and BDE 209 ranged from nondetectable to
      parts per billion. Nevertheless, highly variable procedural blanks were reported
      for the nona-BDEs and BDE 209, which clearly illustrates the importance of
      including blanks repeatedly during determination of these compounds.

PMID- 19102584
TI  - Reproductive health of bass in the Potomac, U.S.A., drainage: part 1. Exploring
      the effects of proximity to wastewater treatment plant discharge.
AB  - Intersex (specifically, testicular oocytes) has been observed in male smallmouth
      bass (SMB; Micropterus dolomieu) and other centrarchids in the South Branch of
      the Potomac River, U.S.A., and forks of the Shenandoah River, U.S.A., during the
      past five years. This condition often is associated with exposure to estrogenic
      endocrine-disrupting chemicals in some fish species, but such chemicals and their
      sources have yet to be identified in the Potomac. In an attempt to better
      understand the plausible causes of this condition, we investigated the
      reproductive health of bass sampled up- and downstream of wastewater treatment
      plant (WWTP) effluent point sources on the Potomac River in Maryland, U.S.A.
      Smallmouth bass were sampled from the Conococheague Creek and the Monocacy River,
      and largemouth bass (LMB; Micropterus salmoides) were collected near the Blue
      Plains WWTP on the mainstem of the Potomac River. Chemical analyses of compounds
      captured in passive samplers at these locations also were conducted. A high
      prevalence of intersex (82-100%) was identified in male SMB at all sites
      regardless of collection area. A lower prevalence of intersex (23%) was
      identified in male LMB collected at the Blue Plains site. When up- and downstream
      fish were compared, significant differences were noted only in fish from the
      Conococheague. Differences included condition factor, gonadosomatic index, plasma
      vitellogenin concentration, and estrogen to testosterone ratio. In general,
      chemicals associated with wastewater effluent, storm-water runoff, and
      agriculture were more prevalent at the downstream sampling sites. An exception
      was atrazine and its associated metabolites, which were present in greater
      concentrations at the upstream sites. It appears that proximity to effluent from
      WWTPs may influence the reproductive health of bass in the Potomac watershed, but
      inputs from other sources likely contribute to the widespread, high incidence of
      testicular oocytes.

PMID- 19102585
TI  - The developmental origins of a disposition toward empathy: Genetic and
      environmental contributions.
AB  - The authors investigated the development of a disposition toward empathy and its
      genetic and environmental origins. Young twins' (N = 409 pairs) cognitive
      (hypothesis testing) and affective (empathic concern) empathy and prosocial
      behavior in response to simulated pain by mothers and examiners were observed at
      multiple time points. Children's mean level of empathy and prosociality increased
      from 14 to 36 months. Positive concurrent and longitudinal correlations indicated
      that empathy was a relatively stable disposition, generalizing across ages,
      across its affective and cognitive components, and across mother and examiner.
      Multivariate genetic analyses showed that genetic effects increased, and that
      shared environmental effects decreased, with age. Genetic effects contributed to
      both change and continuity in children's empathy, whereas shared environmental
      effects contributed to stability and nonshared environmental effects contributed
      to change. Empathy was associated with prosocial behavior, and this relationship
      was mainly due to environmental effects.

PMID- 19102586
TI  - Empathy across the adult lifespan: Longitudinal and experience-sampling findings.
AB  - This study examined change in self-reported empathy in a four-wave longitudinal
      study spanning 12 years (1992-2004) and the association between empathy and other
      measures, including daily reports of relationship experiences. Participants
      initially ranged in age from 10 years to 87 years. Cross-sectional and
      longitudinal associations of age with empathy revealed divergent patterns.
      Whereas cross-sectional analyses suggested that older adults scored lower in
      empathy than younger adults, longitudinal analyses showed no age-related decline
      in empathy. This combined pattern suggests that the cross-sectional age
      differences reflect a cohort rather than an age effect, with older cohorts
      reporting lower levels of empathy than younger ones. Independent of age, empathy
      was associated with a positive well-being (e.g., life satisfaction) and
      interaction profile (e.g., positive relations with others). In addition, a
      subsample of participants (n = 114) conducted experience-sampling about social
      interactions for a week. People with high self-reported empathy perceived their
      interactions as more meaningful, felt more positive in these interactions, and
      thought that their interaction partner felt also more positive. Thus, self
      reported empathy was meaningfully associated with adults' actual social
      interactions.

PMID- 19102587
TI  - Does empathy trigger only altruistic motivation? How about selflessness or
      justice?
AB  - A key question in research on empathy is what interpersonal motivations might be
      activated by empathy. Does empathy promote only a concern with other's outcomes
      ("altruism"), as well as decreased concern with one's own outcomes
      ("selflessness"), or an increased concern with equality in outcomes
      ("egalitarianism")? These interpersonal motivations were assessed with a series
      of experimental games, and our manipulations of empathy paralleled earlier
      research on the empathy-altruism model. Participants received a (fictitious) note
      from another person outlining that he or she is coping with the anticipated loss
      of his or her father in conditions that emphasized taking the other's perspective
      or an objective perspective (high and low empathy), whereas another group of
      participants received no note (no empathy). Consistent with our hypotheses,
      results revealed that a concern with another's well-being (altruism) was greater
      in the two empathy conditions than in the no-empathy condition. Further, the
      authors observed no effect of empathy on selfishness or egalitarianism, two
      motivations that were substantially present independent of empathy. Thus, the
      findings suggest that empathy adds altruistic motivation to already existing
      selfish and egalitarian motivation.

PMID- 19102588
TI  - Inferior frontal gyrus activity triggers anterior insula response to emotional
      facial expressions.
AB  - The observation of movies of facial expressions of others has been shown to
      recruit similar areas involved in experiencing one's own emotions: the inferior
      frontal gyrus (IFG), the anterior insula and adjacent frontal operculum (IFO).
      The causal link between activity in these 2 regions, associated with motor and
      emotional simulation, respectively, has remained unknown. Here using
      psychophysiological interaction and Granger Causality Modeling, we show that
      activity in the IFO is causally triggered by activity in the IFG, and that this
      effective connectivity is specific to the IFG. These findings shed new light on
      the intricate relationship between motor and affective components of emotional
      empathy.

PMID- 19102590
TI  - Support provision in marriage: the role of emotional similarity and empathic
      accuracy.
AB  - The goal of this investigation was to identify microlevel processes in the
      support provider that may foster or inhibit the provision of spousal support.
      Specifically, the authors focused on (a) how emotional similarity between the
      support provider and support seeker and (b) how empathic accuracy of the support
      provider relate to support provision in marriage. In a laboratory experiment, 30
      couples were randomly assigned to 1 of 2 conditions (support provider: man vs.
      woman) of a factorial design. The couples provided questionnaire data and
      participated in a social support interaction designed to assess behaviors when
      offering and soliciting social support. A video-review task was used to assess
      emotional similarity and empathic accuracy during the support interaction. As
      expected, greater similarity between the support provider's and support seeker's
      emotional responses, as well as more accurate insights into the support-seeking
      spouse's thoughts and feelings were found to be predictive of more skilful
      support (i.e., higher levels of emotional and instrumental support and lower
      levels of negative types of support).

PMID- 19102589
TI  - Effects of oxytocin and prosocial behavior on brain responses to direct and
      vicariously experienced pain.
AB  - In this study, we tested the validity of 2 popular assumptions about empathy: (a)
      empathy can be enhanced by oxytocin, a neuropeptide known to be crucial in
      affiliative behavior, and (b) individual differences in prosocial behavior are
      positively associated with empathic brain responses. To do so, we measured brain
      activity in a double-blind placebo-controlled study of 20 male participants
      either receiving painful stimulation to their own hand (self condition) or
      observing their female partner receiving painful stimulation to her hand (other
      condition). Prosocial behavior was measured using a monetary economic interaction
      game with which participants classified as prosocial (N = 12) or selfish (N = 6),
      depending on whether they cooperated with another player. Empathy-relevant brain
      activation (anterior insula) was neither enhanced by oxytocin nor positively
      associated with prosocial behavior. However, oxytocin reduced amygdala activation
      when participants received painful stimulation themselves (in the nonsocial
      condition). Surprisingly, this effect was driven by "selfish" participants. The
      results suggest that selfish individuals may not be as rational and unemotional
      as usually suggested, their actions being determined by their feeling anxious
      rather than by reason.

PMID- 19102591
TI  - Autism and the extraction of emotion from briefly presented facial expressions:
      stumbling at the first step of empathy.
AB  - Identification of other people's emotion from quickly presented stimuli,
      including facial expressions, is fundamental to many social processes, including
      rapid mimicry and empathy. This study examined extraction of valence from brief
      emotional expressions in adults with autism spectrum disorder (ASD), a condition
      characterized by impairments in understanding and sharing of emotions. Control
      participants were individuals with reading disability and typical individuals.
      Participants were shown images for durations in the range of microexpressions (15
      ms and 30 ms), thus reducing the reliance on higher level cognitive skills.
      Participants detected whether (a) emotional faces were happy or angry, (b)
      neutral faces were male or female, and (c) neutral images were animals or
      objects. Individuals with ASD performed selectively worse on emotion extraction,
      with no group differences for gender or animal?object tasks. The emotion
      extraction deficit remains even when controlling for gender, verbal ability, and
      age and is not accounted for by speed-accuracy tradeoffs. The deficit in rapid
      emotional processing may contribute to ASD difficulties in mimicry, empathy, and
      related processes. The results highlight the role of rapid early emotion
      processing in adaptive social?emotional functioning.

PMID- 19102592
TI  - Recognizing masked threat: fear betrays, but disgust you can trust.
AB  - If emotions guide consciousness, people may recognize degraded objects in center
      view more accurately if they either fear the objects or are disgusted by them.
      Therefore, we studied whether recognition of spiders and snakes correlates with
      individual differences in spider fear, snake fear, and disgust sensitivity.
      Female students performed a recognition task with pictures of spiders, snakes,
      flowers, and mushrooms as well as blanks. Pictures were backward masked to reduce
      picture visibility. Signal detection analyses showed that recognition of spiders
      and snakes was correlated with disgust sensitivity but not with fear of spiders
      or snakes. Further, spider fear correlated with the tendency to misinterpret
      blanks as threatening (response bias). These findings suggest that effects on
      recognition and response biases to emotional pictures vary for different emotions
      and emotional traits. Whereas fear may induce response biases, disgust may
      facilitate recognition.

PMID- 19102593
TI  - Attentional bias to threat: a perceptual accuracy approach.
AB  - To investigate attentional bias to threatening information, the authors propose a
      new version of the spatial cueing paradigm in which the focus is on perceptual
      accuracy instead of response speed. In two experiments, healthy volunteers made
      unspeeded discriminations between three visual targets presented left or right.
      Each target was preceded by a visual cue (colored rectangle) at either the same
      (valid) or opposite (invalid) location. By means of differential classical
      conditioning with aversive white noise, a threat cue and a control cue were
      created. Analyses of error rates showed that cueing effects (lower proportion of
      errors in valid trials relative to invalid trials) were more pronounced in threat
      trials than in neutral trials. This threat-related bias was particularly because
      of threat cues reducing accuracy in invalid trials, indicating difficulty
      disengaging attention from threatening information. Engagement of attention was
      not affected by threat, as threat cues did not facilitate the processing of
      targets in valid trials. The findings are discussed in light of the strengths and
      limitations of spatial cueing tasks.

PMID- 19102594
TI  - An investigation of the implicit control of the processing of negative pictures.
AB  - The implicit control of emotion processing was investigated by varying encoding
      instructions for both negative and neutral pictures while measuring
      psychophysiological responses. Participants made comparative judgments about
      consecutive pictures for blocks of neutral or negative content. The highly
      specified judgment task was designed to minimize variance in the implementation
      of implicit control of processing. Affective modulation of startle amplitude was
      significantly reduced during judgments involving nonnegative content (how
      "planned" an image was compared to its predecessor), compared to those that
      involved negative content (how "frightening" an image was compared to its
      predecessor), indicating successful implicit control of processing. The more
      attenuated affect modulation was, the less anxious individuals became during the
      task, suggesting that the implicit control of emotion processing is significantly
      associated with emotional experience. These data provide convergent evidence for
      a companion neuroimaging study because of the similar neural substrates thought
      to underlie affective modulation of startle. This supports the view that higher
      level top-down pathways modulate activation of the amygdala.

PMID- 19102595
TI  - Emotional intelligence, not music training, predicts recognition of emotional
      speech prosody.
AB  - Is music training associated with greater sensitivity to emotional prosody in
      speech? University undergraduates (n = 100) were asked to identify the emotion
      conveyed in both semantically neutral utterances and melodic analogues that
      preserved the fundamental frequency contour and intensity pattern of the
      utterances. Utterances were expressed in four basic emotional tones (anger, fear,
      joy, sadness) and in a neutral condition. Participants also completed an extended
      questionnaire about music education and activities, and a battery of tests to
      assess emotional intelligence, musical perception and memory, and fluid
      intelligence. Emotional intelligence, not music training or music perception
      abilities, successfully predicted identification of intended emotion in speech
      and melodic analogues. The ability to recognize cues of emotion accurately and
      efficiently across domains may reflect the operation of a cross-modal processor
      that does not rely on gains of perceptual sensitivity such as those related to
      music training.

PMID- 19102596
TI  - The emotional harbinger effect: poor context memory for cues that previously
      predicted something arousing.
AB  - A key function of memory is to use past experience to predict when something
      important might happen next. Indeed, cues that previously predicted arousing
      events (emotional harbingers) garner more attention than other cues. However, the
      current series of five experiments demonstrates that people have poorer memory
      for the context of emotional harbinger cues than of neutral harbinger cues.
      Participants first learned that some harbinger cues (neutral tones or faces)
      predicted emotionally arousing pictures and others predicted neutral pictures.
      Then they studied associations between the harbinger cues and new contextual
      details. They were worse at remembering associations with emotional harbingers
      than with neutral harbingers. Memory was impaired not only for the association
      between emotional harbingers and nearby digits, but also for contextual details
      that overlapped with or were intrinsic to the emotional harbingers. However, new
      cues that were inherently emotionally arousing did not yield the same memory
      impairments as the emotional harbingers. Thus, emotional harbinger cues seem to
      suffer more from proactive interference than do neutral harbinger cues, impairing
      formation of new associations with cues that previously predicted something
      arousing.

PMID- 19102598
TI  - Divergent cognitive costs for online forms of reappraisal and distraction.
AB  - The present study was set out to evaluate the cognitive costs of two major
      emotion regulation strategies under conditions of increased challenge. Previous
      studies have established that cognitive reappraisal (construing an emotional
      event in nonemotional terms) has no cognitive costs. However, in all of these
      studies, reappraisal was initiated at the emotional situation onset, before
      emotional response tendencies sufficiently evolved. In the present study, the
      challenge of regulation strategies was increased by initiating strategies online
      at a late time point in an emotional situation. Applying this procedure revealed
      for the first time a cognitive cost for reappraisal and also provided double
      dissociation between reappraisal and another major cognitive emotion regulation
      strategy--distraction (diverting attention from an emotional situation via
      producing neutral thoughts). Specifically, late reappraisal, relative to
      distraction, resulted in an expenditure of self control resources. Late
      distraction but not reappraisal impaired memory encoding of the emotional
      situation.

PMID- 19102597
TI  - Diminished self-conscious emotional responding in frontotemporal lobar
      degeneration patients.
AB  - Frontotemporal lobar degeneration (FTLD) is a neurodegenerative disease that
      dramatically alters social and emotional behavior. Recent work has suggested that
      self-conscious emotions (e.g., embarrassment) may be particularly vulnerable to
      disruption in this disease. Self-conscious emotions require the ability to
      monitor the self in relation to others. These abilities are thought to be
      subserved by brain regions (e.g., medial prefrontal, anterior cingulate, and
      insula) that are particularly vulnerable to damage in FTLD. This study examined
      emotional responding (expressive behavior, peripheral physiology, and subjective
      experience) in 24 FTLD patients and 16 cognitively normal control participants
      using a karaoke task known to elicit self-conscious emotion reliably and a
      nonemotional control task (isometric handgrip). Results indicated that FTLD
      patients showed diminished self-conscious emotional behavior (embarrassment and
      amusement) and diminished physiological responding while watching themselves
      singing. No differences were found between patients and controls in the
      nonemotional control task. These findings offer evidence of marked disruption of
      self-conscious emotional responding in FTLD. Diminished self-conscious emotional
      responding likely contributes significantly to social inappropriateness and other
      behavioral abnormalities in FTLD.

PMID- 19102599
TI  - Looking at or through rose-tinted glasses? Imagery perspective and positive mood.
AB  - We can imagine looking at ourselves (observer perspective) or through our own
      eyes (field perspective). Cognitive and clinical theories suggest that compared
      to field perspective, observer perspective imagery reduces emotional intensity,
      for example, of trauma memories. Tests of causality are lacking and less is known
      about perspective and positive emotion. Using contrasting experimental
      manipulations, participants imagined 100 positive descriptions from either (1) a
      field perspective or (2) an observer perspective, or (3) thought about their
      verbal meaning. Affect was more positive after field than observer imagery and
      verbal conditions, with mood deterioration within the latter two. Findings are
      the first to demonstrate causality of imagery perspective on emotion. Further,
      the results demonstrate that imagining positive events from one's own perspective
      is critical to improving positive affect. Treatment implications include
      promoting field imagery to facilitate a more rose-tinted view of positive events.

PMID- 19102600
TI  - Allocation of spatial attention to emotional stimuli depends upon arousal and not
      valence.
AB  - Attentional allocation to emotional stimuli is often proposed to be driven by
      valence and in particular by negativity. However, many negative stimuli are also
      arousing leaving the question whether valence or arousal accounts for this
      effect. The authors examined whether the valence or the arousal level of
      emotional stimuli influences the allocation of spatial attention using a modified
      spatial cueing task. Participants responded to targets that were preceded by cues
      consisting of emotional pictures varying on arousal and valence. Response
      latencies showed that disengagement of spatial attention was slower for stimuli
      high in arousal than for stimuli low in arousal. The effect was independent of
      the valence of the pictures and not gender-specific. The findings support the
      idea that arousal affects the allocation of attention.

PMID- 19102601
TI  - Embryo donation families: a follow-up in middle childhood.
AB  - Couples who conceive using donated embryos rear a child to whom they are
      genetically unrelated. It has been suggested that this may have negative
      consequences for parenting and child development. Findings are presented of the
      2nd phase of an exploratory study of families with a child conceived through
      embryo donation. Seventeen embryo donation families with a 5- to 9-year-old child
      were compared with 24 adoptive families and 28 in vitro fertilization families.
      The quality of the mother's parenting and the child's social and emotional
      development were assessed using standardized interviews and questionnaires
      administered to mothers and teachers. Embryo donation children were not at
      increased risk of psychological problems during middle childhood, and the
      families were generally functioning well. However, higher emotional
      overinvolvement of embryo donation parents was found, along with more reluctance
      to disclose the method of family creation. These preliminary findings are
      discussed in terms of implications regarding the importance of genetic and
      gestational relationships between parents and children.

PMID- 19102602
TI  - Intimate partner abuse and PTSD symptomatology: examining mediators and
      moderators of the abuse-trauma link.
AB  - Posttraumatic stress disorder (PTSD) has been linked to intimate partner abuse,
      physiological reactivity, and social support. The authors used structural
      equation modeling to test social support as a moderator and psychophysiological
      reactivity and anger as mediators of the relation between abuse and traumatic
      symptoms among a sample of women reporting psychological abuse, including women
      reporting both physical violence and no physical violence. Both physical and
      psychological abuse were related to PTSD symptoms. Whereas physical and
      psychological abuse were highly correlated, psychological abuse did not predict
      PTSD symptomatology over and above the effect due to physical assault.
      Psychophysiological reactivity and anger and fear displayed during an argument
      with the partner did not mediate the abuse?trauma link. Social support moderated
      the relation between psychological abuse and PTSD symptomatology.

PMID- 19102603
TI  - Characterizing the life stressors of children of alcoholic parents.
AB  - The current study examined differences between children of alcoholic (COAs) and
      nonalcoholic parents in their experience of negative life events across 3
      longitudinal studies together spanning the first 3 decades of life. The authors
      posited that COAs would differ from their peers in the life domains in which they
      are vulnerable to stressors, in the recurrence of stressors, and in the severity
      of stressors. Scale- and item-level analyses of adjusted odds ratios based on
      stressors across 7 life domains showed that COAs consistently reported greater
      risk for stressors in the family domain. COAs were also more likely to experience
      stressors repetitively and to rate their stressors as more severe (in adulthood).
      Implications for prevention and intervention programs targeting this risk group
      are discussed.

PMID- 19102604
TI  - What about the kids? Parenting and child adjustment in the context of couple
      therapy.
AB  - Little research examines parenting and children's adjustment when couples engage
      in therapy. We examined how couples with and without children improve with couple
      therapy and whether they also report improvements in parenting and child
      adjustment. With up to twenty six sessions of couple therapy, 134 couples, 68 of
      whom had children, showed improved marital satisfaction during treatment, which
      was ultimately maintained over the 2-year follow-up, regardless of whether they
      had children. Couples married relatively longer, both with and without children,
      evidenced greater improvement. Couples with children reported less conflict over
      child rearing and better child adjustment during treatment, but only improvements
      in the former were maintained. Conflict over child rearing mediated the
      relationship between marital distress and child adjustment over therapy and the 2
      year follow-up. These preliminary results suggest that couples in therapy may
      decrease their conflict over child rearing during treatment and they may be able
      to maintain these gains for at least two years following treatment; moreover,
      over the course of treatment, this decreased conflict is tied to improved child
      adjustment.

PMID- 19102606
TI  - Daily stress, coping, and well-being in parents of children with autism: a
      multilevel modeling approach.
AB  - This study used a repeated daily measurement design to examine the direct and
      moderating effects of coping on daily psychological distress and well-being in
      parents of children with Autism Spectrum Disorders (ASD). Twice weekly over a 12
      week period, 93 parents provided reports of their daily stress, coping responses,
      and end-of-day mood. Multilevel modeling analyses identified 5 coping responses
      (e.g., seeking support, positive reframing) that predicted increased daily
      positive mood and 4 (e.g., escape, withdrawal) that were associated with
      decreased positive mood. Similarly, 2 coping responses were associated with
      decreased daily negative mood and 5 predicted increased negative mood. The
      moderating effects of gender and the 11 coping responses were also examined.
      Gender did not moderate the daily coping?mood relationship, however 3 coping
      responses (emotional regulation, social support, and worrying) were found to
      moderate the daily stress?mood relationship. Additionally, ASD symptomatology,
      and time since an ASD diagnosis were not found to predict daily parental mood.
      This study is perhaps the first to identify coping responses that enhance daily
      well-being and mitigate daily distress in parents of children with ASD.

PMID- 19102605
TI  - Emotional, cognitive, and family systems mediators of children's adjustment to
      interparental conflict.
AB  - Emotional, cognitive, and family systems processes have been identified as
      mediators of the association between interparental conflict and children's
      adjustment. However, little is known about how they function in relation to one
      another because they have not all been assessed in the same study. This
      investigation examined the relations among children's exposure to parental
      conflict, their appraisals of threat and blame, their emotional reaction, and
      triangulation into parental disagreements. One hundred fifty ethnically diverse 8
      to 12-year-old children and both of their parents participated in the study.
      Comparisons of 3 models proposing different relations among these processes
      indicated that they function as parallel and independent mediators of children's
      adjustment. Specifically, children's self-blaming attributions and emotional
      distress were uniquely associated with both internalizing and externalizing
      problems, whereas perceived threat uniquely predicted internalizing problems and
      triangulation uniquely predicted externalizing problems.

PMID- 19102607
TI  - Adolescents' and mothers' perceptions of the cognitive and relational functions
      of collaboration and adjustment in dealing with type 1 diabetes.
AB  - We examined how adolescents' and mothers' perceptions of cognitive and
      interpersonal functions of collaboration surrounding Type 1 diabetes differed and
      how they related to adolescent age, psychosocial, and diabetes adjustment.
      Adolescents (M = 14.16 years) and mothers completed questionnaires assessing the
      functions of collaboration for the adolescent, quality of the mother-adolescent
      relationship, emotional adjustment, and adherence to the diabetes regimen.
      Confirmatory factor analysis (CFA) of perceptions of collaboration confirmed
      three dimensions: collaboration to compensate for cognitive function,
      interpersonal enjoyment, and frequency of collaboration. Although adolescents'
      and mothers' views of interpersonal enjoyment and frequency of collaboration
      converged, their perceptions of compensation were unrelated. Mothers' perceptions
      of adolescents' compensation were unrelated to perceptions of enjoyment and
      frequency. Both adolescents and mothers perceived less compensation and less
      enjoyment of collaboration with increasing adolescent age, but only adolescents
      reported collaborating less frequently with higher age. Better emotional
      adjustment and adherence occurred when mothers and adolescents perceived enjoying
      collaboration (controlling for mothers' acceptance) regardless of age. Enjoying
      collaboration at an interpersonal level may be an important avenue for successful
      diabetes management during adolescence.

PMID- 19102608
TI  - "I'd rather not talk about it": emotion parenting in families of children with an
      anxiety disorder.
AB  - This study examined emotion socialization practices in families of children with
      an anxiety disorder (AD; n = 28) and of children who had no diagnoses (ND; n =
      28) and considered gender differences. Youth (aged 8-13) and both parents
      discussed times when the child felt anxious, angry, and happy, for 5 min each.
      Fathers of AD children engaged in less explanatory discussion of emotion overall
      and exhibited less positive affect and more negative affect when interacting with
      sons than did fathers of ND children. Similar patterns emerged for mothers,
      although specific results varied by emotion type and child gender. Children with
      an AD demonstrated less positive affect overall and engaged in fewer problem
      solving emotion regulation strategies when discussing anxious and angry
      situations than did children in the ND group. In both AD and ND groups, fathers
      appeared to have greater involvement in emotion-related discussions with sons
      versus daughters. The results highlight parents' contributions to the emotional
      development of their children, the ways in which socialization may go awry in
      families of AD children, and the implications for children's emotional
      functioning.

PMID- 19102609
TI  - Features of borderline personality disorder, perceived childhood emotional
      invalidation, and dysfunction within current romantic relationships.
AB  - The mechanisms through which current romantic relationship dysfunction develops
      in individuals with borderline personality disorder (BPD) symptoms are still
      unclear. One possible pathway may be childhood experiences of emotional
      invalidation by parents, which may result in the development of poor social
      problem-solving skills or cognitive responses such as splitting, which impair
      current romantic relationships. This study examines the relationship between
      features of BPD and current romantic relationship dysfunction, and demonstrates
      that perceived emotional invalidation by parents during childhood mediates the
      relationship between BPD features and current romantic relationship dysfunction.
      Structural equations modeling was used to test the hypothesized model in 758
      young adults in an ethnically diverse community sample. The proposed model fit
      the data well; perceived childhood emotional invalidation partially mediated the
      relationship between features of BPD and romantic relationship dysfunction, even
      when controlling for the presence of a major depressive episode in the last year.
      The findings of this study suggest that individuals with features of BPD
      experience relationship dysfunction that cannot be accounted for by comorbid
      depression and that perceived childhood emotional invalidation may contribute to
      these problems.

PMID- 19102610
TI  - Longitudinal moderators of the relationship between excessive drinking and
      intimate partner violence in the early years of marriage.
AB  - Alcohol problems are one of the most well-established risk factors for physical
      intimate partner violence. Nonetheless, most individuals who drink heavily do so
      without ever aggressing against a partner. Laboratory research identifies
      hostility as an important moderator of the association between alcohol and
      general aggression, and correlational research suggests that stress and coping
      may also be important moderators of the alcohol-aggression link. Building on this
      research, the authors examined hostility, coping, and daily hassles as moderators
      of the associations between excessive drinking and intimate partner violence
      across the first 4 years of marriage in a sample of 634 newly married couples.
      Excessive drinking was a significant cross-sectional correlate, but it did not
      emerge as a unique longitudinal predictor of intimate partner violence
      perpetration in this sample. However, alcohol was longitudinally predictive of
      husband violence among hostile men with high levels of avoidance coping. Findings
      generally supported the moderation model, particularly for men. These findings
      implicate hostility, coping, and daily hassles, as well as alcohol, as
      potentially important targets for partner violence prevention strategies for
      young married couples.

PMID- 19102611
TI  - Siblings of adults with mild intellectual deficits or mental illness:
      differential life course outcomes.
AB  - The present study contrasted the later life sibling relationships, patterns of
      family formation, and psychological distress and well-being of siblings of adults
      with disabilities to a nondisabled normative group. The authors identified 268
      siblings of adults with mild intellectual deficits (ID) and 83 siblings of adults
      with mental illness (MI) from the Wisconsin Longitudinal Study (R. M. Hauser & W.
      H. Sewell, 1985; R. M. Hauser, J. Sheridan, & J. R. Warren, 1998), a prospective
      longitudinal study that followed participants from age 18 years to age 64 years.
      Compared with the norm (n = 791), siblings of adults with mild ID had more
      contact with family members and were more likely to live in the same state as the
      sibling with the disability but reported less affective closeness. Siblings of
      adults with MI reported more psychological distress, less psychological well
      being, and less adaptive personality characteristics compared with the norm,
      particularly for siblings of men with MI. There were no differences between
      groups in the patterns of marriage and childbearing.

PMID- 19102612
TI  - Fathers' ratings in the assessment of their child's anxiety symptoms: a
      comparison to mothers' ratings and their associations with paternal
      symptomatology.
AB  - We examined the comparability between mothers' and fathers' ratings in the
      assessment of their child's anxiety symptoms. The sample consisted of 78 youth (6
      to 17 years) and their mothers and fathers who presented to a childhood anxiety
      disorders specialty research clinic. Using intraclass correlation coefficients,
      mother?father agreement of their child's anxiety symptoms was found to be
      moderate. Mean differences between mothers' and fathers' ratings of their child's
      anxiety were not significantly different. Both maternal and paternal self-ratings
      of psychopathology predicted respective ratings of their child's anxiety.
      Although either mothers or fathers can provide useful information, use of
      multiple informants is encouraged, especially when parental psychopathology is
      present. Additional implications and suggestions for future research are
      discussed.

PMID- 19102613
TI  - Chaotic living conditions and sleep problems associated with children's responses
      to academic challenge.
AB  - The ecology of economic disadvantage includes chaotic living conditions that may
      disrupt children's regulatory functioning and undermine mastery oriented
      responses to challenge. The present study examined chaotic living conditions,
      sleep problems, and responses to academic challenge for 96 economically
      disadvantaged children enrolled in a Head Start preschool. Caregiver interviews
      provided information regarding chaotic living conditions of residential crowding,
      noise, and family instability, as well as child sleep problems. Tasks
      individually administered to children provided measures of responses to academic
      challenge. Chaotic living conditions statistically predicted helpless/hopeless
      responses to academic challenge, and sleep problems partially mediated this
      relationship. Implications concern pathways of ecological risk and diversity in
      the school functioning of economically disadvantaged children.

PMID- 19102614
TI  - The effect of interruption duration and demand on resuming suspended goals.
AB  - The time to resume task goals after an interruption varied depending on the
      duration and cognitive demand of interruptions, as predicted by the memory for
      goals model (Altmann & Trafton, 2002). Three experiments using an interleaved
      tasks interruption paradigm showed that longer and more demanding interruptions
      led to longer resumption times in a hierarchical, interactive task. The
      resumption time profile for durations up to 1 min supported the role of decay in
      defining resumption costs, and the interaction between duration and demand
      supported the importance of goal rehearsal in mitigating decay. These findings
      supported the memory for goals model, and had practical implications for context
      where tasks are frequently interleaved such as office settings, driving,
      emergency rooms, and aircraft cockpits.

PMID- 19102615
TI  - The effect of interruptions on postcompletion and other procedural errors: an
      account based on the activation-based goal memory model.
AB  - A postcompletion error (PCE) is a specific kind of cognitive slip that involves
      omitting a final task step after the main goal of the task is accomplished. It is
      notoriously difficult to provoke (and hence study) slips under experimental
      conditions. In this paper, the authors present an experimental task paradigm that
      has been shown to be effective for studying PCEs in routine procedural tasks. Two
      studies were carried out to examine the effect of interruption position and task
      structure on the prevalence of PCEs. It was found that significantly more PCEs
      were obtained when an interruption occurred just before the PC step than when an
      interruption occurred at any other position in the task. The authors account for
      this effect in terms of Altmann and Trafton's activation-based goal memory model.
      The same interruption effect was obtained for some, but not all, other procedural
      errors; the authors discuss the nature of these errors and likely explanations
      for the differences.

PMID- 19102616
TI  - Increased interestingness of extraneous details in a multimedia science
      presentation leads to decreased learning.
AB  - In Experiment 1, students received an illustrated booklet, PowerPoint
      presentation, or narrated animation that explained 6 steps in how a cold virus
      infects the human body. The material included 6 high-interest details mainly
      about the role of viruses in sex or death (high group) or 6 low-interest details
      consisting of facts and health tips about viruses (low group). The low group
      outperformed the high group across all 3 media on a subsequent test of problem
      solving transfer (d = .80) but not retention (d = .05). In Experiment 2, students
      who studied a PowerPoint lesson explaining the steps in how digestion works
      performed better on a problem-solving transfer test if the lesson contained 7 low
      interest details rather than 7 high-interest details (d = .86), but the groups
      did not differ on retention (d = .26). In both experiments, as the
      interestingness of details was increased, student understanding decreased (as
      measured by transfer). Results are consistent with a cognitive theory of
      multimedia learning, in which highly interesting details sap processing capacity
      away from deeper cognitive processing of the core material during learning.

PMID- 19102617
TI  - When does haste make waste? Speed-accuracy tradeoff, skill level, and the tools
      of the trade.
AB  - Novice and skilled golfers took a series of golf putts with a standard putter
      (Exp. 1) or a distorted funny putter (consisting of an s-shaped and arbitrarily
      weighted putter shaft; Exp. 2) under instructions to either (a) take as much time
      as needed to be accurate or to (b) putt as fast as possible while still being
      accurate. Planning and movement time were measured for each putt. In both
      experiments, novices produced the typical speed-accuracy trade-off. Going slower,
      in terms of both the planning and movement components of execution, improved
      performance. In contrast, skilled golfers benefited from reduced performance time
      when using the standard putter in Exp. 1 and, specifically, taking less time to
      plan improved performance. In Exp. 2, skilled golfers improved by going slower
      when using the funny putter, but only when it was unfamiliar. Thus, skilled
      performance benefits from speed instructions when wielding highly familiar tools
      (i.e., the standard putter) is harmed when using new tools (i.e., the funny
      putter), and benefits again by speed instructions as the new tool becomes
      familiar. Planning time absorbs these changes.

PMID- 19102618
TI  - On measuring quantitative interpretations of reasonable doubt.
AB  - Beyond reasonable doubt represents a probability value that acts as the criterion
      for conviction in criminal trials. I introduce the membership function (MF)
      method as a new tool for measuring quantitative interpretations of reasonable
      doubt. Experiment 1 demonstrated that three different methods (i.e., direct
      rating, decision theory based, and MF) provided significantly different and
      uncorrelated interpretations of reasonable doubt, although all methods predicted
      verdicts equally well, and showed inter-individual variability in
      interpretations. In Experiment 2 only the direct rating method demonstrated a
      significant effect of judicial instructions on reasonable doubt. In both
      experiments, the MF method showed intra-individual variability in interpretations
      of reasonable doubt. The methods may be capturing different aspects of the
      concept of reasonable doubt. These findings have implications for the validity of
      past research findings on reasonable doubt and for the utility of triangulation
      of methods in future research.

PMID- 19102619
TI  - Matching faces to photographs: poor performance in eyewitness memory (without the
      memory).
AB  - Eyewitness memory is known to be fallible. We describe 3 experiments that aim to
      establish baseline performance for recognition of unfamiliar faces. In Experiment
      1, viewers were shown live actors or photos (targets), and then immediately
      presented with arrays of 10 faces (test items). Asked whether the target was
      present among the test items, and if so to identify the person, participants
      showed poor performance levels (roughly 70% accurate). Furthermore, there was no
      difference between immediate memory for a live person and photograph. In
      Experiment 2, the same targets and test items were presented simultaneously, and
      participants were asked to perform a matching task. Again, performance was poor
      (roughly 68% accurate), with no difference between matching photos and live
      people. In the final experiment, viewers were asked to match a live person to a
      single photograph. Even under these conditions, performance was poor (c. 85%),
      with no advantage over matching 2 photographs. We suggest that problems of
      eyewitness identification may involve difficulties in initial encoding of
      unfamiliar faces, in addition to problems of memory for an event.

PMID- 19102620
TI  - Adults' memories of childhood: true and false reports.
AB  - In 3 experiments, the authors examined factors that, according to the source
      monitoring framework, might influence false memory formation and true/false
      memory discernment. In Experiment 1, combined effects of warning and
      visualization on false childhood memory formation were examined, as were
      individual differences in true and false childhood memories. Combining warnings
      and visualization led to the lowest false memory and highest true memory. Several
      individual difference factors (e.g., parental fearful attachment style) predicted
      false recall. In addition, true and false childhood memories differed (e.g., in
      amount of information). Experiment 2 examined relations between Deese/Roediger
      McDermott task performance and false childhood memories. Deese/Roediger-McDermott
      performance (e.g., intrusion of unrelated words in free recall) was associated
      with false childhood memory, suggesting liberal response criteria in source
      decisions as a common underlying mechanism. Experiment 3 investigated adults'
      abilities to discern true and false childhood memory reports (e.g., by detecting
      differences in amount of information as identified in Experiment 1). Adults who
      were particularly successful in discerning such reports indicated reliance on
      event plausibility. Overall, the source-monitoring framework provided a viable
      explanatory framework. Implications for theory and clinical and forensic
      interviews are discussed.

PMID- 19102621
TI  - Passenger and cell phone conversations in simulated driving.
AB  - This study examines how conversing with passengers in a vehicle differs from
      conversing on a cell phone while driving. We compared how well drivers were able
      to deal with the demands of driving when conversing on a cell phone, conversing
      with a passenger, and when driving without any distraction. In the conversation
      conditions, participants were instructed to converse with a friend about past
      experiences in which their life was threatened. The results show that the number
      of driving errors was highest in the cell phone condition; in passenger
      conversations more references were made to traffic, and the production rate of
      the driver and the complexity of speech of both interlocutors dropped in response
      to an increase in the demand of the traffic. The results indicate that passenger
      conversations differ from cell phone conversations because the surrounding
      traffic not only becomes a topic of the conversation, helping driver and
      passenger to share situation awareness, but the driving condition also has a
      direct influence on the complexity of the conversation, thereby mitigating the
      potential negative effects of a conversation on driving.

PMID- 19102623
TI  - Three-chromophore excited-state mixed valence.
AB  - The lowest energy optical electronic absorption band of the three-chromophore
      system tris(4-bromophenyl)amine radical cation is analyzed. The lowest energy
      electronic transition corresponds to a p-bromophenyl orbital to nitrogen p
      orbital transition that places the positive charge on three equivalent p
      bromophenyl chromophores. The excited electronic state is an example of excited
      state mixed valence (ESMV), and the spectrum is interpreted using two ESMV
      models. The simplest model invokes the concept of an "effective coupling" between
      the three identical chromophores with an excited-state energy splitting equal to
      three times the coupling. A more accurate model, the "neighboring orbital model",
      utilizes the coupling between the bridge's and charge-bearing unit's orbitals
      closest in energy. The three-chromophore system provides a striking illustration
      of the failure of an effective coupling term to account for ESMV splitting. The
      calculated relative energies of the diabatic and adiabatic states are different,
      but the calculated absorption spectra of the two models show nearly identical
      vibrational fine structure. Resonance Raman data and the time-dependent theory of
      electronic and resonance Raman spectroscopies are used to calculate the spectra.

PMID- 19102624
TI  - Theoretical study of the electronic structure of [tetrathiafulvalene](2)(2+)
      dimers and their long, intradimer multicenter bonding in solution and the solid
      state.
AB  - The long, multicenter bonding in tetrathiafulvalenium cation radical dimers,
      [TTF](2)(2+), observed in both the solid state and in solution, were
      computationally investigated via B3LYP, CASSCF(2,2), and MCQDPT/CASSCF(2,2)
      calculations. The stability of [TTF](2)(2+) dimers originates from
      [TTF](*+)...anion(-) or [TTF](*+)...solvent electrostatic interactions, whose sum
      exceeds the [TTF](*+)...[TTF](*+) repulsion, in solution, or the sum of the
      [TTF](*+)...[TTF](*+) and anion(-)...anion(-) repulsions in solid state.
      MCQDPT/CASSCF(2,2) calculations indicate that the electronic ground state of the
      [TTF](2)(2+) dimers is a closed-shell single state with non-negligible
      contribution of the open-shell singlet, as is experimentally observed. This
      ground state is not well reproduced in B3LYP or CASSCF(2,2) calculations.

PMID- 19102625
TI  - T-cell activation by antigen-loaded pH-sensitive hydrogel particles in vivo: the
      effect of particle size.
AB  - Polymeric carriers designed to encapsulate protein antigens have great potential
      for improving the efficacy of vaccines and immunotherapeutics for diseases such
      as cancer. We recently developed a carrier system based on polyacrylamide
      hydrogel microparticles cross-linked with acid-labile moieties. After being
      phagocytosed by antigen-presenting cells, the protein encapsulated within the
      carrier is released and processed for subsequent presentation of antigenic
      epitopes. To understand the impact of particle size on the activation of T-cells
      following uptake by antigen-presenting cells, particles with mean diameters of
      3.5 microm and 35 nm encapsulating a model protein antigen were synthesized by
      emulsion and microemulsion based polymerization techniques, respectively. In vivo
      tests demonstrated that both sizes of particles were effective at stimulating the
      proliferation of T-cells and were capable of generating an antigen-specific
      cytotoxic T-cell response when coadministered with immunostimulatory DNA.
      Contrary to previous reports in the literature, our results suggest that there is
      no significant difference in the magnitude of T-cell activation for the two sizes
      of particles used in these experiments. This disparity in findings may be related
      to fundamental differences in material properties of the carriers used in these
      studies, such as the hydrophilicity of the polyacrylamide particles described
      here versus the hydrophobic nature of carriers investigated by other groups.

PMID- 19102626
TI  - Stereodynamics and outer valence ionic States of ferrocene in collisional
      ionization with a He*(2(3)S) metastable atom by two-dimensional penning
      ionization electron spectroscopy.
AB  - Outer valence ionic states of ferrocene were investigated by means of Penning
      ionization electron spectroscopy upon collision with metastable He*(2(3)S)
      excited atoms. By two-dimensional measurement combining electron spectroscopy and
      collision-energy-resolved technique of the metastable atomic beam, ionic-state
      resolved measurements of collision energy dependence of partial Penning
      ionization cross sections (CEDPICS) were carried out. Since the partial Penning
      ionization cross sections can be connected with spatial extension of
      corresponding molecular orbitals (MOs) outside the boundary surface for the
      collision with He* atoms, different slope values of CEDPICS were related with
      stereodynamics in Penning ionization as well as anisotropic interaction around
      the ionization region: attractive interaction around ligand pi orbitals and
      repulsive interaction around ligand sigma orbtials and the metal atom. The
      observed negative collision energy dependence of ionization cross sections for
      the first ((2)E(2)') and second ((2)A(1)') ionic states was consistent with
      configuration interactions suggested by ab initio MO calculations [J. Chem. Phys.
      2002, 117, 6533], which is due to the strong electron correlation effects beyond
      the one-electron MO description.

PMID- 19102627
TI  - Dissociative photoionization of methyl thiocyanate, CH3SCN, in the proximity of
      the sulfur 2p edge.
AB  - The dissociative photoionization of gaseous CH3SCN has been investigated at the S
      2p core level using time-of-flight mass spectrometry and synchrotron radiation.
      The total ion yield spectrum could be successfully assigned by comparison with
      available data from electron energy loss spectra. The relative abundances of the
      ionic fragments and their kinetic energy release values were obtained from both
      PEPICO (photoelectron photoion coincidence) and PEPIPICO (photoelectron photoion
      photoion coincidence) spectra. The dynamics of the ionic fragmentation of S 2p
      excited CH3SCN is dominated by the rupture of both carbon-sulfur bonds. This
      process may be related with electronic excitations from the ground electronic
      state to vacant sigma* molecular orbitals.

PMID- 19102628
TI  - Calculation of electronic circular dichroism spectra with time-dependent double
      hybrid density functional theory.
AB  - Time-dependent double-hybrid density functional theory is applied to the
      calculation of the electronic circular dichroism (CD) spectra of molecules. The
      TD-B2PLYP method is based on vertical excitation energies obtained from its
      hybrid-GGA part B2LYP in a conventional TD-DFT linear response treatment and a
      CIS(D) type perturbation correction for these excited states. A new benchmark set
      of six representative organic molecules with a wide variety of different
      electronic character is introduced for this investigation. The simulated TD
      B2PLYP spectra are compared to experiment and those computed with the TD-B2LYP
      (i.e., no CIS(D) correction) and TD-B3LYP methods. Vertical excitation energies
      at the perturbatively corrected level are, in the majority of cases, more
      accurate than, e.g., with TD-B3LYP. Relative band positions are also reproduced
      better. In one example, the high-energy CD bands are not computed with sufficient
      accuracy, which is attributed to an instability of the perturbation correction.
      Due to the inclusion of a large portion of "exact" exchange (53%) in B2PLYP, the
      spectra feature less artificially created excited states and CD bands than with
      TD-B3LYP. In all six examined cases, TD-B2PLYP gives qualitatively correct
      spectra, whereas the hybrid functionals sometimes show a more erratic behavior.
      Therefore, we can recommend the use of the new double-hybrid approach for the
      computation of CD and the prediction of absolute configurations of chiral
      molecules.

PMID- 19102629
TI  - Structural characterizations of glycerol kinase: unraveling phosphorylation
      induced long-range activation.
AB  - Glycerol metabolism provides a central link between sugar and fatty acid
      catabolism. In most bacteria, glycerol kinase plays a crucial role in regulating
      channel/facilitator-dependent uptake of glycerol into the cell. In the firmicute
      Enterococcus casseliflavus, this enzyme's activity is enhanced by phosphorylation
      of the histidine residue (His232) located in its activation loop, approximately
      25 A from its catalytic cleft. We reported earlier that some mutations of His232
      altered enzyme activities; we present here the crystal structures of these mutant
      GlpK enzymes. The structure of a mutant enzyme with enhanced enzymatic activity,
      His232Arg, reveals that residues at the catalytic cleft are more optimally
      aligned to bind ATP and mediate phosphoryl transfer. Specifically, the position
      of Arg18 in His232Arg shifts by approximately 1 A when compared to its position
      in wild-type (WT), His232Ala, and His232Glu enzymes. This new conformation of
      Arg18 is more optimally positioned at the presumed gamma-phosphate location of
      ATP, close to the glycerol substrate. In addition to structural changes exhibited
      at the active site, the conformational stability of the activation loop is
      decreased, as reflected by an approximately 35% increase in B factors ("thermal
      factors") in a mutant enzyme displaying diminished activity, His232Glu.
      Correlating conformational changes to alteration of enzymatic activities in the
      mutant enzymes identifies distinct localized regions that can have profound
      effects on intramolecular signal transduction. Alterations in pairwise
      interactions across the dimer interface can communicate phosphorylation states
      over 25 A from the activation loop to the catalytic cleft, positioning Arg18 to
      form favorable interactions at the beta,gamma-bridging position with ATP. This
      would offset loss of the hydrogen bonds at the gamma-phosphate of ATP during
      phosphoryl transfer to glycerol, suggesting that appropriate alignment of the
      second substrate of glycerol kinase, the ATP molecule, may largely determine the
      rate of glycerol 3-phosphate production.

PMID- 19102630
TI  - The SH3 domain of alphaII spectrin is a target for the Fanconi anemia protein,
      FANCG.
AB  - The structural protein nonerythroid alpha spectrin (alphaIISp) plays a role in
      the repair of DNA interstrand cross-links and is deficient in cells from patients
      with Fanconi anemia (FA), in which there is a defect in ability to repair such
      cross-links. We have proposed a model in which alphaIISp, whose stability is
      dependent on FA proteins, acts as a scaffold to aid in recruitment of repair
      proteins to sites of damage. In order to get a clearer understanding of the
      proposed role of FA proteins in maintaining stability of alphaIISp, yeast two
      hybrid analysis was carried out to determine whether FA proteins directly
      interact with alphaIISp and, if so, to map the sites of interaction. Four
      overlapping regions of alphaIISp were constructed. FANCG interacted with one of
      these regions and specifically with the SH3 domain in this region of alphaIISp.
      The site of interaction in FANCG was mapped to a motif that binds to SH3 domains
      and contains a consensus sequence with preference for the SH3 domain of
      alphaIISp. This site of interaction was confirmed using site-directed
      mutagenesis. Two FA proteins that did not contain motifs that bind to SH3
      domains, FANCC and FANCF, did not interact with the SH3 domain of alphaIISp.
      These results demonstrate that one of the FA proteins, FANCG, contains a motif
      that interacts directly with the SH3 domain of alphaIISp. We propose that this
      binding of FANCG to alphaIISp may be important for the stability of alphaIISp in
      cells and the role alphaIISp plays in the DNA repair process.

PMID- 19102632
TI  - Cyanide-bridged one-dimensional ferromagnetic Ru(III)Mn(III) coordination polymer
      exhibiting a field-induced magnetic phase transition.
AB  - A cyanide-linked Ru(III)(4d)-Mn(III)(3d) bimetallic chain complex (1) was
      prepared by the self-assembly of a ruthenium(III) bicyanide and a Mn(III) Schiff
      base. Ferromagnetic couplings between the magnetic centers are present within a
      chain, while antiferromagnetic interactions between chains (T(N) = 2.5 K)
      transmit. Complex 1 also shows a field-induced magnetic phase transition.

PMID- 19102633
TI  - Should healthcare professionals be advocating long-acting reversible
      contraception?

PMID- 19102631
TI  - Arsenic(III) species inhibit oxidative protein folding in vitro.
AB  - The success of arsenic trioxide in the treatment of acute promyelocytic leukemia
      has renewed interest in the cellular targets of As(III) species. The effects of
      arsenicals are usually attributed to their ability to bind vicinal thiols or
      thiol selenols in prefolded proteins thereby compromising cellular function. The
      present studies suggest an additional, more pleiotropic, contribution to the
      biological effects of arsenicals. As(III) species, by avid coordination to the
      cysteine residues of unfolded reduced proteins, can compromise protein folding
      pathways. Three representative As(III) compounds (arsenite, monomethylarsenous
      acid (MMA), and an aryl arsenical (PSAO)) have been tested with three reduced
      secreted proteins (lysozyme, ribonuclease A, and riboflavin binding protein
      (RfBP)). Using absorbance, fluorescence, and pre-steady-state methods, we show
      that arsenicals bind tightly to low micromolar concentrations of these unfolded
      proteins with stoichiometries of 1 As(III) per 2 thiols for MMA and PSAO and 1
      As(III) for every 3 thiols with arsenite. Arsenicals, at 10 microM, strongly
      disrupt the oxidative folding of RfBP even in the presence of 5 mM reduced
      glutathione, a competing ligand for As(III) species. MMA catalyzes the formation
      of amyloid-like monodisperse fibrils using reduced RNase. These in vitro data
      show that As(III) species can slow, or even derail, protein folding pathways. In
      vivo, the propensity of As(III) species to bind to unfolded cysteine-containing
      proteins may contribute to oxidative and protein folding stresses that are
      prominent features of the cellular response to arsenic exposure.

PMID- 19102634
TI  - Effect of miscarriage on future pregnancies.

PMID- 19102636
TI  - Low-dose estradiol spray: a novel treatment for vasomotor instability in
      postmenopausal women.
AB  - This article describes a novel transdermal estradiol spray developed for the
      treatment of menopausal vasomotor instability. The spray delivers estradiol
      directly into the subcutaneous microcirculation achieving the advantages of
      estradiol patches, creams and gels but with minimal skin reaction, patient
      inconvenience or cosmetic shortcomings associated with transdermal methods. In
      the one published Phase III clinical trial, postmenopausal women (n = 454) with
      eight or more moderate-to-severe hot flashes per day applied each morning, one,
      two or three estradiol 90 microl sprays (each containing estradiol 1.53 mg)
      versus matching placebo sprays. There was a significant decrease in hot flash
      frequency and intensity at weeks 4 and 12 compared with corresponding placebo
      groups (p < 0.010). The systemic estradiol delivery rates at week 12 were
      approximately 0.021, 0.029 and 0.040 mg/day for the 1-, 2- and 3-spray doses,
      respectively. There were common adverse events similar to those previously
      reported with transdermal estradiol, except for skin irritation, which was very
      low. The spray is a well-tolerated, cosmetically attractive and convenient method
      of delivering low-dose, transdermal estradiol.

PMID- 19102637
TI  - Hormone therapy and risk of myocardial infarction.
AB  - Evaluation of: Lokkegaard E, Andreasen AH, Jacobsen RK, Nielsen LH, Agger C,
      Lidegaard O: Hormone therapy and risk of myocardial infarction: a national
      register study. Eur. Heart J. 29(21), 2660-2668 (2008). In a national register
      study of healthy women aged 51-69 years in Denmark followed between 1995 and
      2001, 4947 incident myocardial infarction cases were identified. Overall, there
      was no increased risk of myocardial infarction in current hormone therapy users.
      However, an increased relative risk was observed in younger women (aged 51-54
      years). Overall, the highest risk of myocardial infarction was found with
      continuous hormone therapy. There was no increased risk found with unopposed
      estrogen, cyclical combined therapy or tibolone. A lower risk was found with
      dermal route. However, no associations were found with progestogen type or
      estrogen dose.

PMID- 19102638
TI  - Identifying abdominal aortic aneurysm risk factors in postmenopausal women.
AB  - Evaluation of: Lederle FA, Larson JC, Margolis KL et al.: Abdominal aortic
      aneurysm events in the Women's Health Initiative: cohort study. Br. Med. J. 337,
      A1724 (2008). A linked cohort study of 161,808 postmenopausal women aged 50-79
      years enrolled in the Women's Health Initiative was conducted during which
      participants were followed for the incidence of abdominal aortic aneurysm repair
      or rupture. This study evaluated the association between potential risk factors
      and subsequent abdominal aortic aneurysm events in women. A total of 467 women
      reported a diagnosis of abdominal aortic aneurysm before entering the study or
      during participation, with 184 aneurysm-related events identified. Abdominal
      aortic aneurysm events were strongly associated with age and smoking and
      negatively associated with diabetes and baseline use of postmenopausal hormone
      supplementation. Previous studies investigating abdominal aortic aneurysm have
      focused primarily on men, with little reliable information available on women.
      This study contributes a large female cohort to provide better insight into
      gender-specific abdominal aortic aneurysm risks and disease associations.

PMID- 19102640
TI  - Highest prevalence of vitamin D inadequacy in institutionalized women compared
      with noninstitutionalized women: a case-control study.
AB  - The reduced capacity of older skin to synthesize vitamin D(3) under the influence
      of ultraviolet light makes older persons at risk of vitamin D deficiency. The
      risk could even be increased in institutionalized persons owing to their lower
      sunshine exposure. It has been reported that an inadequate vitamin D level is
      associated with secondary hyperparathyroidism, increased bone turnover, and bone
      loss, which increase fracture risk. The objective of this study was to assess the
      prevalence of inadequate serum vitamin D levels in institutionalized,
      postmenopausal, osteoporotic women. Assessment of 25-hydroxyvitamin D [25(OH)D]
      was performed in 445 institutionalized, osteoporotic women from nine countries
      (Australia, Belgium, France, Germany, Hungary, Italy, Poland, Spain and UK). For
      each institutionalized woman, three age-matched, noninstitutionalized,
      osteoporotic controls were also included. Four cutoffs of 25(OH)D inadequacy were
      fixed: less than 80, less than 75, less than 50 and less than 30 nmol/l. Mean age
      was 79.7 years (standard deviation [SD] = 5.8) for the institutionalized women
      and 79.5 years (SD = 5.5) for the noninstitutionalized women (p = 0.45).
      Significantly fewer institutionalized women received vitamin D supplements (13.2
      vs 24.0%; p < 0.0001). In women without vitamin D supplements, the level of
      25(OH)D was significantly lower in institutionalized women (56.9 [SD = 23.9]
      nmol/l) compared with noninstitutionalized women (63.2 [SD = 22.0] nmol/l; p <
      0.0001). In institutionalized women (without vitamin D supplements), the
      prevalence of 25(OH)D inadequacy was 10.4, 41.2, 80.3 and 84.2% when considering
      cutoffs of 80, 75, 50 and 30 nmol/l, respectively. In the control group, the
      prevalence was 2.7, 22.9, 74.4 and 81.7%, respectively. The prevalence of vitamin
      D inadequacy was significantly higher in institutionalized women when considering
      the 75, 50 and 30 nmol/l cutoffs but not when considering the 80 nmol/l cutoff.
      This study highlights a high prevalence of vitamin D inadequacy in
      institutionalized, osteoporotic women. Compared with age-matched osteoporotic
      controls, the prevalence of severe vitamin D inadequacy was substantially more
      important in institutionalized women. We believe that a greater awareness of the
      importance of vitamin D inadequacy is needed in order to address this public
      health problem.

PMID- 19102639
TI  - Long-term effects of bilateral oophorectomy on brain aging: unanswered questions
      from the Mayo Clinic Cohort Study of Oophorectomy and Aging.
AB  - In the Mayo Clinic Cohort Study of Oophorectomy and Aging, women who had both
      ovaries removed before reaching natural menopause experienced a long-term
      increased risk of parkinsonism, cognitive impairment or dementia, and depressive
      and anxiety symptoms. Here, we discuss five possible mechanistic interpretations
      of the observed associations; first, the associations may be non-causal because
      they result from the confounding effect of genetic variants or of other risk
      factors; second, the associations may be mediated by an abrupt reduction in
      levels of circulating estrogen; third, the associations may be mediated by an
      abrupt reduction in levels of circulating progesterone or testosterone; fourth,
      the associations may be mediated by an increased release of gonadotropins by the
      pituitary gland; and fifth, genetic variants may modify the hormonal effects of
      bilateral oophorectomy through simple or more complex interactions. Results from
      other studies are cited as evidence for or against each possible mechanism. These
      putative causal mechanisms are probably intertwined, and their clarification is a
      research priority.

PMID- 19102641
TI  - Rapid testing at labor and delivery to prevent mother-to-child HIV transmission
      in developing settings: issues and challenges.
AB  - Worldwide, approximately 2.5 million children (95% CI: 2.2-2.6) are living with
      HIV infection. In 2007 alone, approximately 420,000 children (95%CI: 350,000
      540,000) were newly infected with HIV - a vast majority of these infections were
      acquired through maternal-fetal transmission. Many of these infections could have
      been reduced by timely diagnosis and the delivery of interventions aimed at
      preventing mother-to-child HIV transmission. This perspective examines the
      attitudes preventing women from accessing HIV testing early on during pregnancy
      and the issues and challenges that remain in the institutionalization of
      interventions to prevent mother-to-child HIV transmission at labor and delivery.
      Socio-cultural and economic factors prevent women from accessing testing at an
      opportune time during pregnancy. In addition, a lack of adequate infrastructure
      often prevents timely delivery of interventions to those who access testing at
      the last minute (i.e., during labor and delivery). In the wake of a pediatric HIV
      epidemic and the need for lifelong provision of antiretroviral therapy to
      infected children, a simple strategy for provision of round-the-clock rapid
      testing and counseling services in the labor rooms may be cost saving to the
      healthcare systems worldwide.

PMID- 19102642
TI  - Oophorectomy for breast cancer prevention in women with BRCA1 or BRCA2 mutations.
AB  - Owing to the significant breast cancer risk associated with BRCA1 or BRCA2
      mutations, women with these mutations have several options available to them by
      which to reduce the risk of breast cancer. These include surgical (prophylactic
      mastectomy and prophylactic oophorectomy) and medical (chemoprevention) options.
      The breast cancer risk reductions associated with these options range from a 90%
      risk reduction associated with prophylactic mastectomy to approximately 50% with
      oophorectomy or tamoxifen. This article reviews the efficacy of prophylactic
      oophorectomy for the prevention of breast cancer in BRCA1 and BRCA2 mutation
      carriers. The predictors of uptake of the preventive surgery will be discussed,
      in addition to the psychosocial implications of the surgery.

PMID- 19102643
TI  - Migraine and the risk of coronary heart disease and ischemic stroke in women.
AB  - Migraine is a common chronic disorder, especially amongst women - approximately
      18% of US women will have had a migraine attack within the past year.
      Cardiovascular disease is the biggest killer in the same population. This review
      summarizes the best available epidemiological evidence for an independent
      association between migraine and cardiovascular disease amongst women. The most
      reliable evidence comes from the Women's Health Study, which found that migraine
      with aura raised the risk of myocardial infarction by 91% (95% CI: 17-210%) and
      ischemic stroke by 108% (95% CI: 30-231%). Migraine without aura raised both
      risks by approximately 25%. The other prospective studies that were identified
      gave broadly supportive results, and suggested that the risks from migraine were
      attenuated with age. It would be prudent for women who suffer migraine with aura
      to seek medical advice and consider lifestyle changes in order to improve their
      cardiovascular risk profile.

PMID- 19102644
TI  - Gender differences and pain medication.
AB  - Subtle genetic and psychological variations are increasingly recognized to
      contribute to pain and analgesic efficacy and safety. The influence of sex on
      this relationship remains poorly understood, particularly in humans. The issue is
      complicated by the overlay of gender onto physical sex, and its associated
      stereotypes and expectations. Women appear to use more pain-relieving medications
      than men; however, it remains unclear whether these observations represent true
      differences in analgesic usage patterns, or reporting bias. Differences in
      analgesic efficacy relating to body composition, metabolism and hormonal profiles
      have been demonstrated. Psychological and social elements of gender have also
      been associated with altered pain experiences and analgesic use profiles, albeit
      with significant individual variations. Intra-group differences may ultimately
      prove more important than sex differences. Further research may unravel the
      various threads linking gender and sex effects on analgesia with the aim of
      individualizing analgesia to optimize pain relief.

PMID- 19102645
TI  - Corpus luteum hemorrhage in women with bleeding disorders.
AB  - Bleeding into the corpus luteum following ovulation rarely has clinical
      significance in healthy women, but may lead to life-threatening hemorrhage in
      women with congenital or acquired bleeding disorders. Women who are at an
      increased risk for corpus luteum hemorrhage (CLH) can be divided in two
      categories; first, those taking anticoagulants because of a thrombotic disorder;
      and second, women with congenital bleeding disorders. The management and
      prevention of CLH is still unsettled and the literature dealing with this problem
      is based on case reports only. This review focuses on the pathophysiology,
      clinical presentation, diagnosis and treatment options of an acute bleeding event
      and prevention modalities of CLH in women with bleeding disorders.

PMID- 19102647
TI  - On the electric conductivity of highly ordered monolayers of monodisperse metal
      nanoparticles.
AB  - Monolayers of colloidally synthesized cobalt-platinum nanoparticles of different
      diameters characterized by transmission electron microscopy were deposited on
      structured silicon oxide substrates and characterized by scanning electron
      microscopy, grazing incidence X-ray scattering, and electric transport
      measurements. The highly ordered nanoparticle films show a thermally activated
      electron hopping between spatially adjacent particles at room temperature and
      Coulomb blockade at low temperatures. We present a novel approach to
      experimentally determine the particles charging energies giving values of 6.7
      25.4 meV dependent on the particles size and independent of the interparticle
      distance. These observations are supported by finite element method calculations
      showing the self-capacitance to be the determining value which only depends on
      the permittivity constant of the surrounding space and the particles radius.

PMID- 19102648
TI  - Tuning the electronic and molecular structures of catalytic active sites with
      titania nanoligands.
AB  - A series of supported 1-60% TiO(2)/SiO(2) catalysts were synthesized and
      subsequently used to anchor surface VO(x) redox and surface WO(x) acid sites. The
      supported TiO(x), VO(x), and WO(x) phases were physically characterized with TEM,
      in situ Raman and UV-vis spectroscopy, and chemically probed with in situ CH(3)OH
      IR, CH(3)OH-TPSR and steady-state CH(3)OH dehydration. The CH(3)OH chemical probe
      studies revealed that the surface VO(x) sites are redox in nature and the surface
      WO(x) sites contain acidic character. The specific catalytic activity of surface
      redox (VO(4)) and acidic (WO(5)) sites coordinated to the titania nanoligands are
      extremely sensitive to the degree of electron delocalization of the titania
      nanoligands. With decreasing titania domain size, <10 nm, acidic activity
      increases and redox activity decreases due to their inverse electronic
      requirements. This is the first systematic study to demonstrate the ability of
      oxide nanoligands to tune the electronic structure and reactivity of surface
      metal oxide catalytic active sites.

PMID- 19102650
TI  - Nanoengineered carbon scaffolds for hydrogen storage.
AB  - Single-walled carbon nanotube (SWCNT) fibers were engineered to become a scaffold
      for the storage of hydrogen. Carbon nanotube fibers were swollen in oleum (fuming
      sulfuric acid), and organic spacer groups were covalently linked between the
      nanotubes using diazonium functionalization chemistry to provide 3-dimensional (3
      D) frameworks for the adsorption of hydrogen molecules. These 3-D nanoengineered
      fibers physisorb twice as much hydrogen per unit surface area as do typical
      macroporous carbon materials. These fiber-based systems can have high density,
      and combined with the outstanding thermal conductivity of carbon nanotubes, this
      points a way toward solving the volumetric and heat-transfer constraints that
      limit some other hydrogen-storage supports.

PMID- 19102649
TI  - A scFv antibody-based immunoaffinity chromatography column for clean-up of
      bisphenol A-contaminated water samples.
AB  - This is a report on the development of immunoaffinity chromatography using a
      column of silica gel with an immobilized single-chain variable fragment (scFv)
      antibody specific to bisphenol A (BPA) for cleanup of BPA-contaminated water
      samples. The BBA-2187 scFv antibody specific to BPA was purified from the
      periplasmic fractions of the recombinant Escherichia coli. After a sample of BPA
      contaminated river water was applied to the immunoaffinity column, the background
      signal intensity observed in high-performance liquid chromatography (HPLC)
      analysis of the eluates was markedly lower than that observed in HPLC analysis of
      the eluates from an Oasis HLB cartridge treated with the same sample. The
      immunoaffinity column efficiently concentrated BPA from actual river water
      samples with different matrices. Our results demonstrate that the immunoaffinity
      column with immobilized BBA-2187 scFv antibody is efficient for the cleanup of
      BPA-contaminated water samples from different sources.

PMID- 19102651
TI  - Insecticidal action of PF2 lectin from Olneya tesota (Palo Fierro) against
      Zabrotes subfasciatus larvae and midgut glycoconjugate binding.
AB  - Zabrotes subfasciatus (Boheman) is the main pest of common beans (Phaselous
      vulgaris). Some wild legume seeds may contain lectins with insecticidal
      activities against this insect. The larval developments of Z. subfasciatus on
      seeds of Olneya tesota (a desert wild legume) and on artificial seeds containing
      purified PF2 lectin were evaluated. PF2 susceptibility to proteolysis was
      assessed by incubation with midgut extract at different times. PF2 binding to
      midgut glycoconjugates was assessed by histochemistry. A reduced level of
      oviposition and a lack of emergence of adult beetles were observed in O. tesota
      seeds (compared to common beans), and in artificial seeds containing PF2 at 0.5
      and 1%. PF2 was resistant to larval midgut proteolysis for 24 h, while PHA-E
      (lectin control) was fully digested after 4 h. Histochemistry analysis of midguts
      incubated with PF2 showed recognition for microvillae and possibly with
      peritrophic gel. On the other hand, PHA-E exhibited no interaction with larval
      midgut glycoproteins. Proteolysis resistance and glycan recognition could in part
      explain why PF2 is toxic to Z. subfasciatus while PHA is not.

PMID- 19102652
TI  - Pt(II) complexes of a combretastatin A-4 analogous chalcone: effects of
      conjugation on cytotoxicity, tumor specificity, and long-term tumor growth
      suppression.
AB  - Three dichlorido(6-aminomethylnicotinate)platinum complexes 6 comprising a
      combretastatin A-4 analogous chalcone were tested on a panel of 21 tumor cell
      lines from 9 entities. Parent chalcone 1a and the directly linked conjugate 6a
      exhibited excellent antiproliferative activities, similar in magnitude [average
      log(IC(50)) values of -7.3 (1a) and -7.0 (6a)] and cell line specificity but
      slightly different in the mechanism of apoptosis induction. While 1a and 6a
      caused an equally fast rise in caspase-9 in the tested cancer cell lines, the
      downstream effector caspase-3 built up faster in cells treated with 1a compared
      to 6a, yet reached an equal end level. They also had different long-term effects
      on the regrowth of cancer cells treated with a single dose. In contrast,
      conjugates 6b,c featuring longer spacers between the Pt complex and the chalcone
      moieties were less antiproliferative than 6a.

PMID- 19102653
TI  - Oligodeoxyribonucleotide-based antagonists for Toll-like receptors 7 and 9.
AB  - Oligodeoxyribonucleotides containing unmethylated CpG motifs act as TLR9
      agonists. In this study, we evaluated oligonucleotides containing an unmethylated
      CpG motif in which two nucleotides adjacent to the CpG dinucleotide were
      substituted with 2'-O-methylribonucleotides, resulting in TLR7 and TLR9
      antagonists. In mouse and human cell cultures, antagonists did not stimulate
      immune activation but inhibited TLR7 and TLR9 agonist-induced activity. In mice,
      antagonists inhibited immune responses induced by TLR9 agonists for up to several
      days, and the inhibition was dose-dependent. Antagonists also inhibited immune
      responses induced by an RNA-based TLR7/8 agonist but not TLRs 2, 3, 4, or 5
      agonists in mice. Additionally, antagonist inhibited TLR9 agonist-induced IL-6 in
      lupus-prone MRL/lpr mouse spleen cell cultures. These results indicate that
      antagonists described herein can suppress immune responses induced by TLR7 and
      TLR9 agonists. Antagonists may be suitable candidates for treating inflammatory
      and autoimmune diseases where inappropriate or uncontrolled TLR activation has
      been implicated.

PMID- 19102654
TI  - Discovery and structure-activity relationship of P1-P3 ketoamide derived
      macrocyclic inhibitors of hepatitis C virus NS3 protease.
AB  - Hepatitis C virus (HCV) infection is the major cause of chronic liver disease,
      leading to cirrhosis and hepatocellular carcinoma, and affects more than 200
      million people worldwide. Although combination therapy of interferon-alpha and
      ribavirin is reasonably successful in treating majority of genotypes, its
      efficacy against the predominant genotype (genotype 1) is moderate at best, with
      only about 40% of the patients showing sustained virological response. Herein,
      the SAR leading to the discovery of a series of ketoamide derived P(1)-P(3)
      macrocyclic inhibitors that are more potent than the first generation clinical
      candidate, boceprevir (1, Sch 503034), is discussed. The optimization of these
      macrocyclic inhibitors identified a P(3) imide capped analogue 52 that was 20
      times more potent than 1 and demonstrated good oral pharmacokinetics in rats. X
      ray structure of 52 bound to NS3 protease and biological data are also discussed.

PMID- 19102655
TI  - 3-Aryltetronic acids: efficient preparation and use as precursors for vulpinic
      acids.
AB  - 3-Aryltetronic acids were prepared in one step by treatment of a mixture of
      methyl arylacetates and methyl hydroxyacetates with potassium tert-butoxide, via
      tandem transesterification/Dieckmann condensation. Several mushroom or lichen
      pigments, vulpinic acids, were synthesized from 3-(4-methoxyphenyl)tetronic acid
      in three steps involving the reaction of the corresponding dianion with an alpha
      ketoester and the dehydration of the tertiary alcohols obtained into mixtures of
      (E)- and (Z)-alkenes, which were converted under UV irradiation at 254 nm to
      natural (E)-isomers. Syntheses of pinastric acid, 4,4'-dimethoxyvulpinic acid,
      and the first synthesis of recently isolated methyl 3',5'-dichloro-4,4'-di-O
      methylatromentate were hence achieved in an efficient manner.

PMID- 19102656
TI  - Melanin synthesis inhibitors from Lespedeza cyrtobotrya.
AB  - From the roots of Lespedeza cyrtobotrya, 45 flavonoids were isolated along with
      20 new and 25 known compounds. Lipophilic flavonoids 2, 3, 7, 9, 11, 28, 30, and
      39 exhibited strong inhibitory activities on melanin synthesis in normal human
      epidermal melanocytes.

PMID- 19102657
TI  - Toward a chemiluminescent molecular device: metal ion-enhanced chemiluminescence
      of benzylidenacridan with 15-monoazacrown-5.
AB  - The benzylidenacridans (1a-d) with one or more methoxy groups emit light from the
      excited N-methylacridone (NMA) when treated with a solution of sodium
      hypochlorite and alkaline hydrogen peroxide, in which a Hammett relationship with
      a negative rho value was applied between the chemiluminescence quantum yields and
      the sigma values. However, the dimethylamino group drastically inhibited the
      chemiluminescence in spite of its low sigma value. While the compound (2) with 15
      monoazacrown-5 also showed a very weak chemiluminescence upon treatment with
      tetrabutylammonium hydroxide and hydrogen peroxide in acetonitrile, the
      chemiluminescence was enhanced up to 20 times in efficiency when divalent metal
      cations, such as magnesium and calcium ions, were added. The chemiluminescence
      inhibition is proved to be due to the shortening of the fluorescence lifetime of
      NMA due to energy dissipation by the amino substituents, but the incorporation of
      calcium ion into the cavity of the azacrown significantly prolonged the lifetime.
      Thus, the possibility of metal ion sensing by a chemiluminescent molecular device
      is suggested.

PMID- 19102658
TI  - Antisense-guided isolation and structure elucidation of pannomycin, a substituted
      cis-decalin from Geomyces pannorum.
AB  - Antisense-based screening strategies can be used to sensitize a microorganism and
      selectively detect inhibitors against a particular cellular target of interest. A
      strain of Staphylococcus aureus that generates an antisense RNA against SecA,a
      central member of the protein secretion machinery, has been used to screen for
      novel antibacterials. Possible inhibitors of the SecA ATP-ase were selected with
      a high-throughput, two-plate agar-based whole cell differential sensitivity
      screen. After screening a library of over 115 000 natural products extracts with
      the SecA antisense strain, an extract of Geomyces pannorum was identified as
      providing increased activity against the sensitized strain as compared with the
      wild-type control. Bioassay-guided isolation of the active component from this
      fungal extract provided a new cis-decalin secondary metabolite, which we have
      named pannomycin.

PMID- 19102660
TI  - Interactions of arenes and thioethers resulting in facilitated oxidation.
AB  - Synthesis of 6-endo and 6-exomethylthio-2-endoarylbicyclo[2.2.1]heptanes was
      accomplished stereoselectively. The ionization energies, determined by
      photoelectron spectroscopy, and electrochemical oxidation potentials, determined
      by cyclic voltammetry, were lower for the 6-endomethylthio compounds than for
      their 6-exomethylthio analogues. Calculations supported the notion that
      facilitation of electron transfer in the 6-endomethylthio compounds results from
      through-space S...pi interaction.

PMID- 19102659
TI  - Effects of ectopic Nanog and Oct4 overexpression on mesenchymal stem cells.
AB  - Mesenchymal stem cells (MSCs) represent a source of pluripotent cells that are
      already in various phases of clinical application. However, the use of MSCs in
      tissue engineering has been hampered largely due to their limitations, including
      low proliferation, finite life span, and gradual loss of their stem cell
      properties during ex vivo expansion. Nanog and Oct4 are key transcription factors
      essential to the pluripotent and self-renewing phenotypes of undifferentiated
      embryonic stem cells (ESCs). To determine whether Nanog and Oct4 improve human
      bone marrow-MSC quality, we therefore established stable Nanog and Oct4
      overexpressing MSCs using a lentiviral system and showed that this promoted cell
      proliferation and enhanced colony formation of MSCs. In differentiating MSCs,
      Nanog, and Oct4, overexpression had converse effects on adipogenesis of MSCs and
      Nanog overexpression slowed down adipogenesis, whereas Oct4 overexpression
      improved adipogenesis. Nanog and Oct4 overexpression both improved
      chondrogenesis. Microarray data showed many differences in transcriptional
      targets in undifferentiated MSCs overexpressing Nanog and Oct4. These results
      provide insight into the improvement of the stemness of MSCs by genetic
      modification with stemness-related genes.

PMID- 19102661
TI  - A simple base-mediated halogenation of acidic sp2 C-H bonds under noncryogenic
      conditions.
AB  - A new method has been developed for in situ halogenation of acidic sp(2) carbon
      hydrogen bonds in heterocycles and electron-deficient arenes. Either selective
      monohalogenation or one-step exhaustive polyhalogenation is possible for
      substrates possessing several C-H bonds that are flanked by electron-withdrawing
      groups. For the most acidic arenes, such as pentafluorobenzene, K(3)PO(4) base
      can be employed instead of BuLi for metalation/halogenation sequences.

PMID- 19102663
TI  - Neuregulin-1 signaling in schizophrenia: 'Jack of all trades' or master of some?

PMID- 19102665
TI  - Use of long-acting risperidone in psychiatric disorders: focus on efficacy,
      safety and cost-effectiveness.
AB  - Schizophrenia is a chronic disorder, usually necessitating lifelong treatment.
      Although atypical antipsychotic agents have improved outcomes in schizophrenia,
      their clinical potential remains limited by patients' nonadherence to medication.
      Long-acting antipsychotics were developed in the 1960s to enhance treatment
      adherence and simplify the medication process. However, although conventional
      long-acting agents assure medication delivery, they are associated with similar
      side effects to their oral equivalents. The need for an agent combining the
      advantages of a long-acting formulation with those of an atypical antipsychotic
      was highlighted in 1997 by the American Psychiatric Association's Practice
      Guideline for the Treatment of Patients with Schizophrenia. The first long-acting
      injectable atypical antipsychotic, long-acting risperidone (Risperdal Consta,
      Johnson & Johnson), has since been developed. This article discusses the
      efficacy, tolerability and cost-effectiveness of long-acting risperidone in
      schizophrenia and bipolar disorder patients, and suggests possibilities for how
      its role in clinical practice may change over the next 5 years.

PMID- 19102666
TI  - Lacosamide: pharmacology, mechanisms of action and pooled efficacy and safety
      data in partial-onset seizures.
AB  - Lacosamide is an antiepileptic drug approved in the USA and Europe as adjunctive
      therapy for partial-onset seizures. Studies suggest that lacosamide selectively
      enhances slow inactivation of voltage-gated sodium channels and possibly
      interacts with collapsin response mediator protein-2. The efficacy of lacosamide
      has been shown in animal models of epilepsy and Phase II/III clinical trials.
      Pharmacokinetic studies show that it is renally excreted, minimally bound to
      plasma proteins and has no known clinically relevant drug-drug interactions.
      Clinical trials show that lacosamide is well tolerated; the most common adverse
      events were dizziness, nausea and vomiting. In a Phase II/III pooled analysis,
      lacosamide 200 and 400 mg/day significantly reduced partial-onset seizure
      frequency and improved the 50% responder rate compared with placebo.

PMID- 19102667
TI  - The 2008 annual meeting of the International Society for Pediatric Neurosurgery:
      highlights of the oncology session.
AB  - The International Society for Pediatric Neurosurgery (ISPN) was founded in 1972
      with the intention of becoming an international organization joining
      neurosurgeons interested in pediatric neurosurgery from all over the world. Since
      its foundation, the ISPN organizes an annual meeting and the location of this
      conference rotates between the five continents. This year's 36th annual meeting
      took place in Cape Town, South Africa, and focused on different topics, including
      pediatric neuro-oncology, which is the subject of this report.

PMID- 19102668
TI  - Treatment of schizophrenia in the 21st Century: beyond the neurotransmitter
      hypothesis.
AB  - Over the last six decades, the treatment of schizophrenia has focused primarily
      on interactions at monoamine neurotransmitter receptor sites, including those for
      dopamine and serotonin. While first-generation antipsychotics demonstrate
      antagonism at the dopamine 2 receptor, newer atypical agents involve multiple
      receptors at various neurotransmitter sites. Despite the advent of these newer
      agents, the treatment of schizophrenia continues to elude clinicians, perhaps
      owing to a lack of information about the factors contributing to the development
      of the disease. While the etiology is complex and not yet fully delineated, we
      suggest that treating clinicians be willing to look beyond neurotransmitters and
      entertain other potential factors involved in the pathogenesis of schizophrenia.
      One such factor that is often overlooked is the possible contribution of
      autoimmunity to disease development in at least a subset of patients. In this
      article we make an argument for consideration of immune dysfunction in the
      development of schizophrenia and suggest future directions for the field.

PMID- 19102669
TI  - Adjunctive lithium and anticonvulsants for the treatment of schizophrenia: what
      is the evidence?
AB  - Lithium and anticonvulsants are used as adjunctive agents to antipsychotic
      medications for the treatment of schizophrenia. However, the evidence supporting
      this 'off-label' use is relatively shallow and inconsistent. Early reports of the
      usefulness of lithium as an adjunctive agent have been negated by later studies.
      Similarly, large trials of adjunctive valproate and adjunctive lamotrigine
      completed in the wake of early and promising efficacy signals from smaller
      studies have failed to replicate the initial findings. Also problematic is the
      dearth of large trials of adjunctive mood stabilizers in treatment-refractory
      schizophrenia or persistent aggressive behavior in schizophrenia, two populations
      for which there remains a pressing therapeutic need for effective medication
      regimens. Nevertheless, on an individual patient basis there may be some benefits
      to be gained by adding a mood stabilizer to a medication regimen, but these must
      be weighed against potential adverse effects, and outcomes closely monitored so
      that discontinuation of the mood stabilizer is prompt should benefits not accrue.

PMID- 19102670
TI  - Role of the cholinergic system in the pathology and treatment of schizophrenia.
AB  - Schizophrenia is a devastating psychiatric disorder; the diagnosis probably
      encompasses a number of illnesses with similar clinical presentations,
      complicating both treatment and studies into the pathology of the disorder. The
      development of antipsychotic medications revolutionized treatment for the
      disorder. However, there are still symptom domains that are relatively untouched
      by the drugs currently available; these are the cognitive deficits and the
      negative symptoms. Basic research strongly supports a role of acetylcholine in
      cognitive processes, making it a primary target for drugs designed to improve
      this most impairing symptom. In addition, the fact that acetylcholine can
      modulate dopamine release makes the cholinergic system a target for novel
      antipsychotic drugs, ideally without the side-effect profiles that contribute to
      patient noncompliance seen with current antipsychotic drugs. Thus far, the
      results of clinical trials with cholinomimetics have been equivocal; where
      beneficial effects are seen they are, by and large, modest rather than
      compelling. These trials and studies investigating the role of both nicotinic and
      muscarinic receptors in the pathology of the disorder, published during the last
      5 years, are reviewed to ascertain whether there is a role for the cholinergic
      system in the treatment of schizophrenia.

PMID- 19102671
TI  - GABAergic promoter hypermethylation as a model to study the neurochemistry of
      schizophrenia vulnerability.
AB  - The neuronal GABAergic mechanisms that mediate the symptomatic beneficial effects
      elicited by a combination of antipsychotics with valproate (a histone deacetylase
      inhibitor) in the treatment of psychosis (expressed by schizophrenia or bipolar
      disorder patients) are unknown. This prompted us to investigate whether the
      beneficial action of this combination results from a modification of histone tail
      covalent esterification or is secondary to specific chromatin remodeling. The
      results suggest that clozapine, or sulpiride associated with valproate, by
      increasing DNA demethylation with an unknown mechanism, causes a chromatin
      remodeling that brings about a beneficial change in the epigenetic GABAergic
      dysfunction typical of schizophrenia and bipolar disorder patients.

PMID- 19102672
TI  - Obsessive-compulsive symptoms in schizophrenia: prevalence, correlates and
      treatment.
AB  - Literature from the turn of the 20th Century to the present suggests that
      obsessive-compulsive symptoms occur among persons with schizophrenia at rates
      that far exceed what is found among persons not suffering from psychoses. Less
      clear, however, is the significance of those symptoms. Are obsessive-compulsive
      symptoms, for instance, related to other aspects of schizophrenia or do they
      represent another isolated dimension of distress? To address this issue, a review
      of studies is presented that explores the relationships between obsessive
      compulsive symptoms; positive, negative and depressive symptoms; psychosocial
      dysfunction; and neurocognitive deficits. Results are interpreted as indicating
      that obsessive-compulsive symptoms are linked with graver impairments in
      psychosocial function. Regarding the relationship between obsessive-compulsive
      symptoms and neurocognition, results from across a broad range of studies are
      equivocal. A review of studies of pharmacological treatments for obsessive
      compulsive symptoms has also failed to produce consistent results. While some
      agents have been found to lead to improvement in obsessive-compulsive symptoms,
      other studies suggest that these medications may exacerbate those same symptoms.
      In general, it appears that, at best, there are currently few effective
      treatments. Directions for future research are reviewed. Recommendations include
      the development of tailored psychological and psychopharmacological
      interventions, and the implementation of longitudinal studies sensitive to the
      possibility that there are qualitatively distinct groups of patients with
      schizophrenia and obsessive-compulsive symptoms.

PMID- 19102673
TI  - Assessment and treatment of suicide risk in bipolar disorders.
AB  - Completed suicide and suicide attempts are major issues in the management of
      bipolar disorders. There is evidence that suicide rates among these patients are
      more than 20-fold higher than the general population and, furthermore, suicidal
      behavior is much more lethal in bipolar disorder than in the general population.
      Patients with mood disorders may sometimes exhibit highly perturbed mixed states,
      which usually increase the risk of suicide. Such states are particularly frequent
      in bipolar II patients, especially if patients are treated with antidepressant
      monotherapy (unprotected by mood stabilizers), when depression switches into
      mania (or vice versa), or when depression lifts and functioning approaches
      normality. Researchers worldwide agree that treatment involving lithium is the
      best way to protect patients from suicide risk. Psychosocial activities,
      including psychoeducation, can protect bipolar patients either directly or, more
      probably, indirectly by increasing adherence to treatment and helping in daily
      difficulties that otherwise may lead to demoralization or hopelessness. An
      extensive understanding of the psychosocial circumstances and the psychopathology
      of bipolar patients (including temperament) may help clinicians describe the
      clinical picture accurately and prevent suicidal behavior in these patients.

PMID- 19102674
TI  - Fracture risks of antidepressants.
AB  - Antidepressants come in a variety of types, the main types being tricyclic
      antidepressants (TCAs), selective serotonin reuptake inhibitors (SSRIs) and the
      group of other antidepressants. Among the TCAs, only amitriptyline seems to be
      associated with an increased risk of fractures, which is probably linked to an
      increased risk of falls. SSRIs seem to be associated with an increased risk of
      fractures as a class effect. An early increase probably linked to falls is
      observed within the first 14 days of initiating a SSRI, but also a sustained
      small increase in the risk of fractures seems present with SSRIs. The group of
      other antidepressants did not seem to be systematically associated with
      fractures, although a small increase may be seen for some types early after
      initiation. The alterations in risk of fractures were small and differences
      between preparations limited. In the interpretation, the effect of confounding by
      indication should be remembered; patients with depression may have an increased
      risk of fractures per se.

PMID- 19102676
TI  - Diastereoselective preparation of substituted delta-valerolactones. synthesis of
      (3R,4S)- and (3R,4R)-simplactones.
AB  - The syntheses of simplactones (3R,4S)-1 and (3R,4R)-2 were achieved in 5 steps
      from N-acyl thiazolidinethione chiral auxiliaries. The syntheses feature a double
      diastereoselective acetate aldol reaction solely controlled by the chirality of
      the auxiliary. Highly diastereoselective aldol reactions with s-trioxane were
      also achieved with N-acyl thiazolidinethione auxiliaries and the stereochemistry
      of an aldol product confirmed by X-ray analysis.

PMID- 19102678
TI  - Calibration of modern density functional theory methods for the prediction of
      57Fe Mossbauer isomer shifts: meta-GGA and double-hybrid functionals.
AB  - Five density functionals including GGA (generalized gradient approximation)
      (BP86), meta-GGA (TPSS), hybrid meta-GGA (TPSSh), hybrid (B3LYP), and double
      hybrid functionals (B2PLYP) were calibrated for the prediction of 57Fe Mossbauer
      isomer shifts on a set of 20 iron-containing molecules. The influence of scalar
      relativistic effects and the basis set dependence of the predictions were
      investigated.

PMID- 19102677
TI  - Multiple Ca(2+)-binding sites in the extracellular domain of the Ca(2+)-sensing
      receptor corresponding to cooperative Ca(2+) response.
AB  - A small change in the extracellular Ca(2+) concentration ([Ca(2+)](o)) integrates
      cell signaling responses in multiple cellular and tissue networks and functions
      via activation of Ca(2+)-sensing receptors (CaSR). Mainly through binding of
      Ca(2+) to the large extracellular domain (ECD) of the dimeric CaSR, intracellular
      Ca(2+) responses are highly cooperative with an apparent Hill coefficient ranging
      from 2 to 4. We have previously reported the identification of two continuous
      putative Ca(2+)-binding sites by grafting CaSR-derived, Ca(2+)-binding peptides
      to a scaffold protein, CD2, that does not bind Ca(2+). In this paper, we predict
      more potential noncontinuous Ca(2+)-binding sites in the ECD. We dissect the
      intact CaSR into three globular subdomains, each of which contains two to three
      predicted Ca(2+)-binding sites. This approach enables us to further understand
      the mechanisms underlying the binding of multiple metal ions to extended
      polypeptides derived from a location within the ECD of the CaSR, which would be
      anticipated to more closely mimic the structure of the native CaSR ECD. Tb(3+)
      luminescence energy transfer, ANS fluorescence, and NMR studies show biphasic
      metal-binding components and Ca(2+)-dependent conformational changes in these
      subdomains. Removing the predicted Ca(2+)-binding ligands in site 1 and site 3
      abolishes the first binding step and second binding step, respectively. Studies
      on these subdomains suggest the existence of multiple metal-binding sites and
      metal-induced conformational changes that might be responsible for the switching
      on and off the CaSR by the transition between its open inactive form and closed
      active form.

PMID- 19102679
TI  - Phosphine polymerization by nitric oxide: experimental characterization and
      theoretical predictions of mechanism.
AB  - A yellow solid material [P(x)H(y)] has been obtained in the reaction of phosphine
      (PH(3)) and nitric oxide (NO) at room temperature and characterized by
      thermogravimetric analysis mass spectrometry (TGA-MS) and attenuated total
      reflection Fourier transform infrared (ATR-FTIR) spectroscopy. In this work using
      complete basis set (CBS-QB3) methods a plausible mechanism has been investigated
      for phosphine polymerization in the presence of nitric oxide (NO). Theoretical
      explorations with the ab initio method suggest (a) instead of the monomer the
      nitric oxide dimer acts as an initial oxidant, (b) the resulting phosphine oxides
      (H(3)P=O <--> H(3)P(+)O(-)) in the gas phase draw each other via strong dipolar
      interactions between the P-O groups, and (c) consequently an autocatalyzed
      polymerization occurs among the phosphine oxides, forming P-P chemical bonds and
      losing water. The possible structures of polyhydride phosphorus polymer were
      discussed. In the calculations a series of cluster models was computed to
      simulate polymerization.

PMID- 19102681
TI  - Cyclosporins from Mycelium sterilae MS 2929.
AB  - The structures of two new cyclosporins were elucidated by NMR and MS methods as
      cyclo[-MeBmt(1)-Abu(2)-Sar(3)-MeLeu(4)-Val(5)-MeLeu(6)-Ala(7)-d-Ala(8)-MeLeu(9)
      MeNva(10)-MeVal(11)-] and cyclo[-MeBmt(1)-Abu(2)-Sar(3)-MeLeu(4)-Abu(5)-MeLeu(6)
      Ala(7)-d-Ala(8)-MeLeu(9)-MeLeu(10)-MeVal(11)-].

PMID- 19102680
TI  - Effect of guggulsterone and cembranoids of Commiphora mukul on pancreatic
      phospholipase A(2): role in hypocholesterolemia.
AB  - Guggulsterone (7) and cembranoids (8-12) from Commiphora mukul stem bark resin
      guggul were shown to be specific modulators of two independent sites that are
      also modulated by bile salts (1-6) to control cholesterol absorption and
      catabolism. Guggulsterone (7) antagonized the chenodeoxycholic acid (3)-activated
      nuclear farnesoid X receptor (FXR), which regulates cholesterol metabolism in the
      liver. The cembranoids did not show a noticeable effect on FXR, but lowered the
      cholate (1)-activated rate of human pancreatic IB phospholipase A2 (hPLA2), which
      controls gastrointestinal absorption of fat and cholesterol. Analysis of the data
      using a kinetic model has suggested an allosteric mechanism for the rate increase
      of hPLA2 by cholate and also for the rate-lowering effect by certain bile salts
      or cembranoids on the cholate-activated hPLA2 hydrolysis of phosphatidylcholine
      vesicles. The allosteric inhibition of PLA2 by certain bile salts and cembranoids
      showed some structural specificity. Biophysical studies also showed specific
      interaction of the bile salts with the interface-bound cholate-activated PLA2.
      Since cholesterol homeostasis in mammals is regulated by FXR in the liver for
      metabolism and by PLA2 in the intestine for absorption, modulation of PLA2 and
      FXR by bile acids and selected guggul components suggests novel possibilities for
      hypolipidemic and hypocholesterolemic therapies.

PMID- 19102683
TI  - Reaction discovery employing macrocycles: transannular cyclizations of
      macrocyclic bis-lactams.
AB  - Macrocyclic bis-lactams have been synthesized by cyclodimerization of homoallylic
      amino esters employing a Zr(IV)-catalyzed ester-amide exchange protocol. Base
      mediated transannular cyclizations have been identified to access both bicyclic
      [5-11] and tricyclic [5-8-5] frameworks in good yield and diastereoselectivity.
      Preliminary mechanistic studies support an olefin isomerization-intramolecular
      conjugate addition pathway.

PMID- 19102682
TI  - Enhancing the divergent activities of betulinic acid via neoglycosylation.
AB  - Using neoglycosylation, the impact of differential glycosylation upon the
      divergent anticancer and anti-HIV properties of the triterpenoid betulinic acid
      (BA) was examined. Each member from a library of 37 differentially glycosylated
      BA variants was tested for anticancer and anti-HIV activities. Enhanced analogs
      for both desired activities were discovered with the corresponding antitumor or
      antiviral enhancements diverging, on the basis of the appended sugar, into two
      distinct compound subsets.

PMID- 19102684
TI  - Short communication: Absence of evidence of HTLV-3 and HTLV-4 in patients with
      large granular lymphocyte (LGL) leukemia.
AB  - Clonal disorders of large granular lymphocytes (LGL) result in leukemia due to
      the expansion of a discrete subset of either CD3(+) T cells or natural killer
      (NK) cells. It has been hypothesized that a viral antigen acts as the initial
      stimulus causing the expansion of these cells. The possible involvement of human
      T cell lymphotropic virus types 1 and 2 (HTLV-1 and HTLV-2) in this disease has
      been studied but no conclusive evidence has linked either virus with LGL
      leukemia. In this study, we examined whether HTLV-3 or HTLV-4, two newly
      identified HTLV groups discovered in Central Africa in primate hunters, is
      involved in LGL leukemia. We developed two specific real-time PCR quantitative
      assays that are highly sensitive, capable of detecting 10 copies of HTLV-3 or
      HTLV-4 pol sequences in a background of 1 microg of DNA from human peripheral
      blood lymphocytes (PBL). We tested PBL DNA samples from 40 LGL leukemia patients
      in the United States and found that all samples were negative for HTLV-3 or HTLV
      4 infection. These results suggest that HTLV-3 and HTLV-4 are not the causative
      agent of LGL leukemia.

PMID- 19102685
TI  - Short communication: In vitro synergy between peptides or neutralizing antibodies
      targeting the N- and C-terminal heptad repeats of HIV Type 1 gp41.
AB  - Class 1 and class 2 fusion peptides bind to the trimeric N-terminal heptad repeat
      (NHR) and C-terminal heptad repeat (CHR) regions of HIV-1 envelope glycoprotein
      gp41, respectively, and block its intramolecular folding required for Env
      mediated viral and host cell membrane fusion and subsequent viral entry. Using a
      combination of T-20 (class 1) and (CCIZN17)(3) (class 2), we provide evidence
      that these classes of fusion peptides work synergistically in an in vitro
      infectivity assay in inhibiting the entry of primary HIV-1 isolate 89.6 with
      combination indexes reaching 0.37 and 0.32 at IC(50) and IC(90), respectively. We
      further demonstrate a similar degree of neutralization synergy between a
      monoclonal antibody (MAb), D5, targeting the hydrophobic pocket region of the
      NHR, and 2F5, a well-characterized MAb that targets the C-terminal end of CHR and
      the membrane-proximal external region (MPER), providing a rational basis for
      developing combination vaccines targeting these two highly conserved regions of
      gp41.

PMID- 19102686
TI  - Fetal allostimulation of maternal cells: a potential mechanism for perinatal HIV
      transmission following obstetrical hemorrhage.
AB  - Our aim was to elucidate the mechanism by which HIV transmission is increased
      following obstetrical hemorrhage. We investigated whether fetal allostimulation
      of maternal cells, which could occur following fetal-to-maternal hemorrhage,
      increases proliferation, HIV replication, and cellular activation. Peripheral
      blood mononuclear cells (PBMCs) were collected from HIV-infected mothers and
      their infants to assess maternal-fetal allostimulation. Responses were compared
      to allostimulation with unrelated donors. Maternal and fetal cells were
      cocultured to assess allogeneic stimulation. Cell proliferation was measured by
      [(3)H]thymidine incorporation and cell activation was assessed via fluorochrome
      labeled antibody staining and flow cytometric analysis. Virus production from HIV
      infected maternal cells was quantitated by p24 enzyme-linked immunosorbent assay
      or by branched chain DNA assay. Allostimulation with fetal cells led to maternal
      cell proliferation. In women with unsuppressed viral loads, virus release was
      also enhanced following allostimulation of maternal cells with fetal cells. Fetal
      cells are capable of allogeneically stimulating maternal cells, with responses
      comparable to those seen following allostimulation with unrelated donors.
      Allostimulation of maternal cells by fetal cells results in statistically
      significant increases in proliferation and enhanced HIV replication, suggesting a
      possible physiological mechanism for mother-to-child transmission of HIV in women
      with obstetrical hemorrhage.

PMID- 19102687
TI  - Prevalence of nevirapine-associated resistance mutations after single dose
      prophylactic treatment among antenatal clinic attendees in north rift Kenya.
AB  - The use of single dose nevirapine to prevent mother-to-child transmission of HIV
      has been reported to induce drug-resistant mutations and reduce options for
      antiretroviral treatment for HIV-infected mothers and their children. To explore
      the status of nevirapine-resistant HIV genotypes in rural hospitals in the North
      Rift Valley Province of Kenya, samples collected 3 months after single dose
      nevirapine from 36 mothers and their children were analyzed. Resistance mutations
      were genotypically evaluated through proviral DNA amplification, cloning, and
      sequencing. Ten mothers (27.8%) had antiretroviral-associated resistance
      mutations of whom four (11.1%) had specific nevirapine (NNRTI) resistance
      associated mutations. Three mothers (8.3%) transmitted the infection to their
      infants. This presence of nevirapine mutations in rural antenatal clinic
      attendees confirms the importance of integrating antiretroviral resistance
      monitoring as a key component in programs geared to prevention of HIV mother-to
      child transmission.

PMID- 19102689
TI  - Conjugation of latent membrane protein (LMP)-2 epitope to gold nanoparticles as
      highly immunogenic multiple antigenic peptides for induction of Epstein-Barr
      virus-specific cytotoxic T-lymphocyte responses in vitro.
AB  - Nasopharyngeal carcinoma is a neoplasm with a high incidence in Southeast Asia,
      and it is strongly associated with Epstein-Barr virus (EBV) activation involving
      the expression of a weakly immunogenic protein, namely, latent membrane protein
      (LMP)-2. Previous immunological studies already identified the human leukocyte
      antigen (HLA)-A11 restricted peptide epitope (SSCSSCPLSK) in the LMP-2 antigen.
      In this work, we prepared gold nanoparticle (AuNP)-peptide conjugate 1 by
      treating the nanoparticles with the N-cysteinated LMP-2 epitope. The AuNP-peptide
      conjugates have been characterized by TEM (15-24 nm in diameter) and UV-vis
      spectroscopy (surface plasmon resonance absorption band at lambda(max) = 520 nm).
      In the presence of a CALNN capping peptide, the AuNP-peptide conjugates are
      stable in solution without aggregation at room temperature for at least 48 h. By
      ELIspot studies, AuNP-peptide conjugate 1 was found to elicit a significantly
      stronger INF-gamma response [number of spot forming cells (SPC) = 727 +/- 198]
      from peripheral blood mononuclear cells of healthy HLA-A11 donors when compared
      to that induced by the unconjugated LMP-2 peptides (SFC = 73 +/- 28). Further
      studies showed that dendritic cells treated with conjugate 1 can effect CD8+ T
      cell activation leading to epitope-specific cytotoxic T lymphocyte killing
      responses in vitro.

PMID- 19102688
TI  - HIV type 1 genetic diversity in Moyale, Mandera, and Turkana based on env-C2-V3
      sequences.
AB  - The genetic diversity of HIV-1 subtypes circulating in three districts of
      northern Kenya, i.e., Turkana, Mandera, and Moyale, was studied. DNA sequences
      encoding a portion of the env-C2-V3 region of the virus were amplified by PCR and
      sequenced directly. One hundred and fifty-nine samples were successfully
      sequenced in the env-C2-V3 region and analyzed. From the analysis, 57% were
      subtype A1, 27% were subtype C, 9% were subtype D, and the remaining 7% were
      unclassified. This study showed that HIV-1 subtype A1 was the dominant subtype in
      circulation in this region, though there was a significant percentage of HIV-1
      subtype C in circulation there.

PMID- 19102690
TI  - Mechanism of the iron-mediated alkene aziridination reaction: experimental and
      computational investigations.
AB  - Combined experimental and computational studies suggest that the iron-mediated
      aziridination of cis-1-phenylpropene proceeds along two mechanistic pathways that
      share a common imidoiron(IV) intermediate. One pathway involves a second species,
      proposed to be an azametallacyclobutane intermediate, which collapses to provide
      the syn-aziridine product. A second, parallel pathway is responsible for the
      formation of an anti-aziridine.

PMID- 19102691
TI  - Controlling the phase and amplitude of plasmon sources at a subwavelength scale.
AB  - We present a new class of nanoscale plasmonic sources based on subwavelength
      dielectric cavities embedded in a metal slab. Exploiting the strong dispersion
      near the Fabry-Perot resonance in such a resonator, we control the phase and the
      amplitude of the generated plasmons at the subwavelength scale. As an example, we
      present a subwavelength unidirectional plasmonic antenna utilizing interference
      between two plasmonic cavity sources with matched phase and amplitude.

PMID- 19102692
TI  - The QTAIM approach to chemical bonding between transition metals and carbocyclic
      rings: a combined experimental and theoretical study of (eta(5)-C5H5)Mn(CO)3,
      (eta(6)-C6H6)Cr(CO)3, and (E)-{(eta(5)-C5H4)CF=CF(eta(5)-C5H4)}(eta(5)-C5H5)2Fe2.
AB  - Experimental charge densities for (C(5)H(5))Mn(CO)(3) (2), (eta(6)
      C(6)H(6))Cr(CO)(3) (3), and (E)-{(eta(5)-C(5)H(4))CF=CF(eta(5)-C(5)H(4))}(eta(5)
      C(5)H(5))(2)Fe(2) (4) have been obtained by multipole refinement of high
      resolution X-ray diffraction data at 100 K. The resultant densities were analyzed
      using the quantum theory of atoms in molecules (QTAIM). The electronic structures
      of these and related pi-hydrocarbyl complexes have also been studied by ab initio
      density functional theory calculations, and a generally good agreement between
      theory and experiment with respect to the topological parameters was observed.
      The topological parameters indicate significant metal-ring covalency. A
      consistent area of disagreement concerns the topology of the metal-ring
      interactions. It is shown that because of the shared-shell bonding between the
      metal and the ring carbons, an annulus of very flat density rho and very small
      wedge rho is formed, which leads to topologically unstable structures close to
      catastrophe points. This in turn leads to unpredictable numbers of metal-C bond
      paths for ring sizes greater than four and fewer M-C bond paths than expected on
      the basis of the formal hapticity. This topological instability is a general
      feature of metal-pi-hydrocarbyl interactions and means that a localized approach
      based on individual M-C(ring) bond paths does not provide a definitive picture of
      the chemical bonding in these systems. However, other QTAIM indicators, such as
      the virial paths, the delocalization indices, and the source function, clearly
      demonstrate that for the n-hapto (eta(n)-C(n)H(n))M unit, there is generally a
      very similar level of chemical bonding for all M-C(ring) interactions, as
      expected on the basis of chemical experience.

PMID- 19102693
TI  - Mass measurement errors of Fourier-transform mass spectrometry (FTMS):
      distribution, recalibration, and application.
AB  - The hybrid linear trap quadrupole Fourier-transform (LTQ-FT) ion cyclotron
      resonance mass spectrometer, an instrument with high accuracy and resolution, is
      widely used in the identification and quantification of peptides and proteins.
      However, time-dependent errors in the system may lead to deterioration of the
      accuracy of these instruments, negatively influencing the determination of the
      mass error tolerance (MET) in database searches. Here, a comprehensive discussion
      of LTQ/FT precursor ion mass error is provided. On the basis of an investigation
      of the mass error distribution, we propose an improved recalibration formula and
      introduce a new tool, FTDR (Fourier-transform data recalibration), that employs a
      graphic user interface (GUI) for automatic calibration. It was found that the
      calibration could adjust the mass error distribution to more closely approximate
      a normal distribution and reduce the standard deviation (SD). Consequently, we
      present a new strategy, LDSF (Large MET database search and small MET
      filtration), for database search MET specification and validation of database
      search results. As the name implies, a large-MET database search is conducted and
      the search results are then filtered using the statistical MET estimated from
      high-confidence results. By applying this strategy to a standard protein data set
      and a complex data set, we demonstrate the LDSF can significantly improve the
      sensitivity of the result validation procedure.

PMID- 19102694
TI  - Parallel synthesis and screening of polymers for nonviral gene delivery.
AB  - We describe the parallel synthesis and in vitro evaluation of a cationic polymer
      library for the discovery of nonviral gene delivery vectors. The library was
      synthesized based on the ring-opening polymerization reaction between epoxide
      groups of diglycidyl ethers and the amines of (poly)amines. Parallel screening of
      soluble library constituents led to the identification of lead polymers with high
      DNA-binding efficacies. Transfection efficacies of lead polymers were evaluated
      using PC3-PSMA human prostate cancer cells and murine osteoblasts in the absence
      and presence of serum. In vitro experiments resulted in the identification of a
      candidate polymer that demonstrated significantly higher transfection efficacies
      and lower cytotoxicities than poly(ethyleneimine) (pEI), the current standard for
      polymeric transfection agents. In addition, polymers that demonstrated moderately
      higher and comparable transfection efficacies with respect to pEI were also
      identified. Our results demonstrate that high-throughput synthesis and screening
      of polymers is a powerful approach for the identification of novel nonviral gene
      delivery agents.

PMID- 19102695
TI  - Probing protein conformations by in situ non-covalent fluorescence labeling.
AB  - The conformational dynamics of proteins plays a key role in their complex
      physiological functions. Fluorescence resonance energy transfer (FRET) is a
      particular powerful tool for studying protein conformational dynamics, but
      requires efficient site-specific labeling with fluorescent reporter probes. We
      have employed different tris-NTA/fluorophore conjugates, which bind histidine
      tagged proteins with high affinity, for site-specific incorporation of FRET
      acceptors into proteins, which were covalently labeled with a donor fluorophore.
      We demonstrate versatile application of this approach for exploring the
      conformation of the type I interferon receptor ectodomains ifnar1-EC and ifnar2
      EC. Substantial ligand-induced conformational changes of ifnar1-EC, but not
      ifnar2-EC, were observed by monitoring the fluorescence intensity and the
      fluorescence lifetime of the FRET donor. Time-resolved fluorescence correlation
      spectroscopy revealed a substantial conformational flexibility of ifnar1-EC and a
      ligand-induced tightening. Our results demonstrate that protein labeling with
      tris-NTA/fluorophores enables for efficient quantitative intramolecular FRET
      analysis.

PMID- 19102696
TI  - Selective synthesis of single-crystalline rhombic dodecahedral, octahedral, and
      cubic gold nanocrystals.
AB  - This paper reports a versatile seed-mediated growth method for selectively
      synthesizing single-crystalline rhombic dodecahedral, octahedral, and cubic gold
      nanocrystals. In the seed-mediated growth method, cetylpyridinium chloride (CPC)
      and CPC-capped single-crystalline gold nanocrystals 41.3 nm in size are used as
      the surfactant and seeds, respectively. The CPC-capped gold seeds can avoid
      twinning during the growth process, which enables us to study the correlations
      between the growth conditions and the shapes of the gold nanocrystals. Surface
      energy and kinetic considerations are taken into account to understand the
      formation mechanisms of the single-crystalline gold nanocrystals with varying
      shapes. CPC surfactants are found to alter the surface energies of gold facets in
      the order {100} > {110} > {111} under the growth conditions in this study,
      whereas the growth kinetics leads to the formation of thermodynamically less
      favored shapes that are not bounded by the most stable facets. The competition
      between AuCl(4)(-) reduction and the CPC capping process on the {111} and {110}
      facets of gold nanocrystals plays an important role in the formation of the
      rhombic dodecahedral (RD) and octahedral gold nanocrystals. Octahedral
      nanocrystals are formed when the capping of CPC on {111} facets dominates, while
      RD nanocrystals are formed when the reduction of AuCl(4)(-) on {111} facets
      dominates. Cubic gold nanocrystals are formed by the introduction of bromide ions
      in the presence of CPC. The cooperative work of cetylpyridinium and bromide ions
      can stabilize the gold {100} facet under the growth condition in this study,
      thereby leading to the formation of cubic gold nanocrystals.

PMID- 19102697
TI  - Single-step method for the isolation and surface functionalization of cellulosic
      nanowhiskers.
AB  - Surface modification of cellulosic nanowhiskers (CNW) is of great interest,
      especially to facilitate their use as polymer reinforcements. Generally,
      alteration of the surface chemistry is performed using multiple reaction steps.
      In contrast, this study demonstrates that the needed hydrolysis of amorphous
      cellulose chains can be performed simultaneously with the esterification of
      accessible hydroxyl groups to produce surface functionalized CNW in a single
      step. The reaction is carried out in an acid mixture composed of hydrochloric and
      an organic acid (acetic and butyric are both demonstrated). Resulting CNW are of
      similar dimensions compared to those obtained by hydrochloric acid hydrolysis
      alone; sizes are verified by multiangle laser-light scattering and transmission
      electron microscopy. However, narrower diameter polydispersity indices indicate
      that surface groups aid the individualization of the nanowhiskers (Px = 2.5 and
      2.1 for acetic and butyric acid, Px = 3.0 for hydrochloric acid). More than half
      of the hydroxyl groups located on the CNW surface are substituted under the
      employed reaction conditions as determined by quantitative Fourier-transform
      infrared-spectroscopy. The resulting surface modified CNW are dispersible in
      ethyl acetate and toluene indicating increased hydrophobicity and thus are
      presumably more compatible with hydrophobic polymers when used as a reinforcing
      phase.

PMID- 19102698
TI  - Discovery of 1-[9-(4-chlorophenyl)-8-(2-chlorophenyl)-9H-purin-6-yl]-4
      ethylaminopiperidine-4-carboxylic acid amide hydrochloride (CP-945,598), a novel,
      potent, and selective cannabinoid type 1 receptor antagonist.
AB  - We report the structure-activity relationships, design, and synthesis of the
      novel cannabinoid type 1 (CB1) receptor antagonist 3a (CP-945,598). Compound 3a
      showed subnanomolar potency at human CB1 receptors in binding (Ki = 0.7 nM) and
      functional assays (Ki = 0.12 nM). In vivo, compound 3a reversed cannabinoid
      agonist-mediated responses, reduced food intake, and increased energy expenditure
      and fat oxidation in rodents.

PMID- 19102699
TI  - Total synthesis and biological evaluation of tubulysin U, tubulysin V, and their
      analogues.
AB  - A stereoselective total synthesis of the cytotoxic natural products tubulysin U,
      tubulysin V, and its unnatural epimer epi-tubulysin V, is reported. Simplified
      analogues containing N,N-dimethyl-D-alanine as a replacement for the N-terminal N
      Me-pipecolinic acid residue of the tubulysins are also disclosed. Biological
      evaluation of these natural products and analogues provided key information with
      regard to structural and stereochemical requirements for antiproliferative
      activity and tubulin polymerization inhibition.

PMID- 19102700
TI  - Syntheses and properties of the new electron transfer sensitizers 4,2'
      pyrylogens.
AB  - The syntheses and characterizations of the 4,2'-regioisomers of the dicationic
      pyrylogen electron transfer sensitizers are reported. The electrochemical and
      photophysical properties of these sensitizers are compared to the previously
      reported 4,4'-pyrylogens.

PMID- 19102701
TI  - Chemical doping and electron-hole conduction asymmetry in graphene devices.
AB  - We investigate poly(ethylene imine) and diazonium salts as stable, complementary
      dopants on graphene. Transport in graphene devices doped with these molecules
      exhibits asymmetry in electron and hole conductance. The conductance of one
      carrier is preserved, while the conductance of the other carrier decreases.
      Simulations based on nonequilibrium Green's function formalism suggest that the
      origin of this asymmetry is imbalanced carrier injection from the graphene
      electrodes caused by misalignment of the electrode and channel neutrality points.

PMID- 19102702
TI  - Novel Au-Ag hybrid device for electrochemical SE(R)R spectroscopy in a wide
      potential and spectral range.
AB  - A nanostructured gold-silver-hybrid electrode for SER spectroelectrochemistry was
      developed which advantageously combines the electrochemical properties and
      chemical stability of Au and the strong surface enhancement of (resonance) Raman
      scattering by Ag. The layered device consists of a massive nanoscopically rough
      Ag electrode, a thin (2 nm) organic layer, and a ca. 20 nm thick Au film that may
      be coated by self-assembled monolayers for protein adsorption. The SERR
      spectroscopic and electrochemical performance of this device is demonstrated
      using the heme protein cytochrome c as a benchmark model system, thereby
      extending, for the first time, SE(R)R studies of molecules on Au surfaces to
      excitation in the violet spectral range. The enhancement factor is only slightly
      lower than for Ag electrodes which can be rationalized in terms of an efficient
      transfer of plasmon resonance excitation from the Ag to the Au coating. This
      mechanism, which requires a thin dielectric layer between the two metals, is
      supported by theoretical calculations.

PMID- 19102703
TI  - Functional tuning of photoactive yellow protein by active site residue 46.
AB  - Protein-ligand interactions alter the properties of active site groups to achieve
      specific biological functions. The active site of photoactive yellow protein
      (PYP) provides a model system for studying such functional tuning. PYP is a small
      bacterial photoreceptor with photochemistry based on its p-coumaric acid (pCA)
      chromophore. The absorbance maximum and pK(a) of the pCA in the active site of
      native PYP are shifted from 400 nm and 8.8 in water to 446 nm and 2.8 in the
      native protein milieu, respectively, by protein-ligand interactions. We report
      high-throughput microscale methods for the purification and spectroscopic
      investigation of PYP and use these to examine the role of active site residue
      Glu46 in PYP, which is hydrogen bonded to the pCA anion. The functional and
      structural attributes of the 19 substitution mutants of PYP at critical active
      site position 46 vary widely, with absorbance maxima from 441 to 478 nm, pCA
      fluorescence quantum yields from 0.19 to 1.4%, pCA pK(a) values from 3.0 to 9.0,
      and protein folding stabilities from 6.5 to 12.9 kcal/mol. The kinetics of the
      last photocycle transition vary by more than 4 orders of magnitude and are often
      strongly biphasic. Only E46Q PYP exhibits a greatly accelerated photocycling
      rate. All substitutions yield a folded, photoactive PYP, illustrating the
      robustness of protein structure and function. Correlations between side chain and
      mutant properties establish the importance of residue 46 in tuning the function
      of PYP and the significance of the strength of its hydrogen bond to the pCA.
      Native PYP exhibits the lowest values for pCA fluorescence quantum yield and
      pK(a), indicating their functional relevance. These results demonstrate the value
      of quantitative high-throughput biophysical studies of proteins.

PMID- 19102705
TI  - A PAS domain with an oxygen labile [4Fe-4S](2+) cluster in the oxygen sensor
      kinase NreB of Staphylococcus carnosus.
AB  - The cytoplasmic histidine sensor kinase NreB of Staphylococcus carnosus responds
      to O(2) and controls together with the response regulator NreC the expression of
      genes of nitrate/nitrite respiration. nreBC homologous genes were found in
      Staphylococcus strains and Bacillus clausii, and a modified form was found in
      some Lactobacillus strains. NreB contains a sensory domain with similarity to
      heme B binding PAS domains. Anaerobically prepared NreB of S. carnosus exhibited
      a (diamagnetic) [4Fe-4S](2+) cluster when assessed by Mossbauer spectroscopy.
      Upon reaction with air, the cluster was degraded with a half-life of
      approximately 2.5 min. No significant amounts of Mossbauer or EPR detectable
      intermediates were found during the decay, but magnetic Mossbauer spectra
      revealed formation of diamagnetic [2Fe-2S](2+) clusters. After extended exposure
      to air, NreB was devoid of a FeS cluster. Photoreduction with deazaflavin
      produced small amounts of [4Fe-4S](+), which were degraded subsequently. The
      magnetically perturbed Mossbauer spectrum of the [4Fe-4S](2+) cluster
      corroborated the S = 0 spin state and revealed uniform electric field gradient
      tensors of the iron sites, suggesting full delocalization of the valence
      electrons and binding of each of the Fe ions by four S ligands, including the
      ligand to the protein. Mutation of each of the four Cys residues inactivated NreB
      function in vivo in accordance with their role as ligands. [4Fe-4S](2+) cluster
      containing NreB had high kinase activity. Exposure to air decreased the kinase
      activity and content of the [4Fe-4S](2+) cluster with similar half-lives. We
      conclude that the sensory domain of NreB represents a new type of PAS domain
      containing a [4Fe-4S](2+) cluster for sensing and function.

PMID- 19102704
TI  - Correlating AMPA receptor activation and cleft closure across subunits: crystal
      structures of the GluR4 ligand-binding domain in complex with full and partial
      agonists.
AB  - AMPA receptors are glutamate-gated ion channels that are essential mediators of
      synaptic signals in the central nervous system. They form tetramers that are
      assembled as combinations of subunits GluR1-4, each of which contains a ligand
      binding domain (LBD). Crystal structures of the GluR2 LBD have revealed an
      agonist-binding cleft, which is located between two lobes and which acts like a
      Venus flytrap. In general, agonist efficacy is correlated with the extent of
      cleft closure. However, recent observations show that cleft closure is not the
      sole determinant of the relative efficacy for glutamate receptors. In addition,
      these studies have focused on the GluR2 subunit, which is the specific target of
      a physiologically important RNA-editing modification in vivo. We therefore sought
      to test the generality of the cleft closure-efficacy correlation for other AMPA-R
      subunits. Here, we present crystal structures of the GluR4(flip) LBD in complex
      with both full and partial agonists. As for GluR2, both agonists stabilize a
      closed-cleft conformation, and the partial agonist induces a smaller cleft
      closure than the full agonist. However, a detailed analysis of LBD-kainate
      interactions reveals the importance of subtle backbone conformational changes in
      the ligand-binding pocket in determining the magnitude of agonist-associated
      conformational changes. Furthermore, the GluR4 subunit exhibits a different
      correlation between receptor activation and LBD cleft closure than does GluR2.

PMID- 19102706
TI  - Distinct domains in HMGB1 are involved in specific intramolecular and nucleosomal
      interactions.
AB  - HMGB1 is composed of two DNA-binding domains and a long acidic tail at the C
      terminus. The acidic tail interacts with the DNA-binding domains of HMGB1 and
      with core histone H3 in the nucleosome. These interactions are important for
      modulation of the DNA and chromatin binding activities of HMGB1, as well as
      biological functions of HMGB1. However, the interactions are not fully
      characterized, because the tertiary structure of full-length HMGB1 is still
      unknown. Here we use chemical cross-linking, mass spectrometry, and epitope
      masking analysis to perform a detailed characterization of the inter- and
      intramolecular protein interactions of the acidic tail of HMGB1. We show that
      specific regions of the acidic tail participate in intramolecular interactions
      with Lys2 of HMGB1 and in intermolecular interactions with Lys36 and Lys37 of
      histone H3. The acidic tail is oriented by its location adjacent to the C
      terminus of helix III of DNA-binding HMG box A in the HMGB1 molecule. These
      results suggest that the acidic tail modulates the biological functions of HMGB1
      through these specific interactions.

PMID- 19102707
TI  - Setting future standards for KRAS testing in colorectal cancer.

PMID- 19102709
TI  - Dr Roger Klein speaks to Tarryn Greenberg, Commissioning Editor. Interview.

PMID- 19102711
TI  - Pharmacogenetics of debrisoquine and its use as a marker for CYP2D6 hydroxylation
      capacity.
AB  - Debrisoquine hydroxylation polymorphism is by far the most thoroughly studied
      genetic polymorphism of the CYP2D6 drug-metabolizing enzyme. Debrisoquine
      hydroxylation phenotype has been the most used test in humans to evaluate CYP2D6
      activity. Two debrisoquine hydroxylation phenotypes have been described: poor and
      extensive metabolizers. A group with a very low debrisoquine metabolic ratio
      within the extensive metabolizers, named ultrarapid metabolizers, has also been
      distinguished. This CYP2D6 variability can be for a large part alternatively
      determined by genotyping, which appears to be of clinical importance given CYP2D6
      involvement in the metabolism of a large number of commonly prescribed drugs.
      CYP2D6 pharmacogenetics may then become a useful tool to predict drug-related
      side effects, interactions or therapeutic failures. However, a number of reasons
      appear to have made research into this field lag behind. The present review
      focuses on the relevance of genetics and environmental factors for determining
      debrisoquine hydroxylation phenotype, as well as the relevance of CYP2D6 genetic
      polymorphism in psychiatric patients treated with antipsychotic drugs.

PMID- 19102712
TI  - Glutathione S-transferase T1- and M1-null genotypes and coronary artery disease
      risk in patients with Type 2 diabetes mellitus.
AB  - INTRODUCTION: Since long-term exposure to oxidative stress is strongly implicated
      in the pathogenesis of diabetic complications, polymorphic genes of detoxifying
      enzymes must be involved in the development of coronary artery disease (CAD). We
      assessed the potential glutathione S-transferase (GST) gene-gene (GSTM1(null)
      GSTT1(null)) and gene-smoking interactions on the development of CAD in patients
      with Type 2 diabetes. MATERIALS & METHODS: In a case-only design, we enrolled 231
      patients with Type 2 diabetes (147 male, 66.1 +/- 9.7 years) referred to our
      institute for coronary angiography investigation. CAD was diagnosed if there was
      over 50% obstruction of one or more major vessels. RESULTS: Coronary angiography
      revealed significant CAD in 184 patients (80%). Male gender (p < 0.001), smoking
      habits (p = 0.003) and GSTT1(null) genotype (p = 0.003) were significantly
      correlated with the increasing extent of the coronary atherosclerosis. Case-only
      analysis revealed that patients with both M(null)-T(null) genotypes had the
      highest risk for 3-vessel CAD compared with patients who express both GST genes
      (odds ratio: 3.1; 95% confidence interval: 1.0-10.3, p = 0.04). A nearly
      threefold interaction existed between cigarette smoking and M(null)-T(null)
      genotypes (odds ratio: 2.9, 95% confidence interval: 1.7-7.8, p = 0.03). A
      significant interaction between M(null)-T(null) genotypes and smoking was also
      observed on the increasing number of coronary vessels that were diseased (chi(2)
      = 14.0; p = 0.03). CONCLUSION: These data suggest that polymorphisms in GSTM1 and
      GSTT1 genes are risk factors for CAD in Type 2 diabetic patients, especially
      among smokers. These genetic markers may permit the targeting of preventive and
      early intervention on high-risk patients to reduce their cardiovascular risk.

PMID- 19102713
TI  - A Bayesian approach to gene-gene and gene-environment interactions in chronic
      fatigue syndrome.
AB  - INTRODUCTION: In the study of genomics, it is essential to address gene-gene and
      gene-environment interactions for describing the complex traits that involves
      disease-related mechanisms. In this work, our goal is to detect gene-gene and
      gene-environment interactions resulting from the analysis of chronic fatigue
      syndrome patients' genetic and demographic factors including SNPs, age, gender
      and BMI. MATERIALS & METHODS: We employed the dataset that was original to the
      previous study by the Centers for Disease Control and Prevention Chronic Fatigue
      Syndrome Research Group. To investigate gene-gene and gene-environment
      interactions, we implemented a Bayesian based method for identifying significant
      interactions between factors. Here, we employed a two-stage Bayesian variable
      selection methodology based on Markov Chain Monte Carlo approaches. RESULTS: By
      applying our Bayesian based approach, NR3C1 was found in the significant two
      locus gene-gene effect model, as well as in the significant two-factor gene
      environment effect model. Furthermore, a significant gene-environment interaction
      was identified between NR3C1 and gender. These results support the hypothesis
      that NR3C1 and gender may play a role in biological mechanisms associated with
      chronic fatigue syndrome. CONCLUSION: We demonstrated that our Bayesian based
      approach is a promising method to assess the gene-gene and gene-environment
      interactions in chronic fatigue syndrome patients by using genetic factors, such
      as SNPs, and demographic factors such as age, gender and BMI.

PMID- 19102714
TI  - Need for reassessment of reported CYP2C19 allele frequencies in various
      populations in view of CYP2C19*17 discovery: the case of Greece.
AB  - INTRODUCTION: CYP2C19*17 is a novel variant allele causing ultrarapid metabolism
      of CYP2C19 substrates. In the present study we investigated the CYP2C19*17
      allelic frequency and recalculated previously reported frequencies of the
      CYP2C19*1/*1 genotype and of all genotype-derived phenotypes for CYP2C19 in the
      Greek population. MATERIALS & METHODS: A total of 283 nonrelated healthy Greek
      ethnic subjects that had already been genotyped for CYP2C19*2 and *3 alleles as
      well as for CYP2D6 and CYP2C9 variant alleles participated in the study. The
      CYP2C19*17 allele was genotyped by the PCR-RFLP method. RESULTS: The CYP2C19*17
      allele frequency was 19.61%. The prevalence of CYP2C19*17 carriers in the Greek
      population was estimated at 31.80%, while the frequency of CYP2C19*1/*1 genotype
      was recalculated to 44.17% from 75.97% in our previous study. Several subjects
      possessing both CYP2C19*17 and variant alleles of CYP2D6 and CYP2C9 were also
      identified. DISCUSSION & CONCLUSION: The CYP2C19*17 allele is present in Greeks
      at a high frequency similar to that found in other European populations of
      Caucasian origin. Our study highlights the need of reassessing and updating
      CYP2C19 allelic frequencies in various populations in view of the major role that
      CYP2C19*17 may have in predicting the clinical outcome of drugs metabolized by
      CYP2C19.

PMID- 19102715
TI  - Measurements of EGFR expression on circulating tumor cells are reproducible over
      time in metastatic breast cancer patients.
AB  - AIMS: Studies of EGFR expression in breast cancer have shown inconsistent results
      due in part to a large range of methods used. Anti-EGFR therapy trials have often
      not used patient selection because of this. We describe the use of the CellSearch
      system (Veridex LLC, NJ, USA) to enumerate and measure EGFR expression on the
      surface of circulating tumor cells (CTCs), derived from the peripheral blood of
      individuals with metastatic breast cancer over time. MATERIALS & METHODS: The
      CellSearch system was used to quantify CTCs and EGFR measurement was performed on
      all samples. The specificity of EGFR phenotyping was further examined by spiking
      with cell lines with increased and low (or absent) levels of EGFR expression
      using the CellSearch system to enrich and phenotype the CTCs. RESULTS: Serial
      samples were obtained from 33 individuals with metastatic breast cancer. CTCs
      derived from these individuals had consistent levels of EGFR expression at
      different time points, and none of the patients 'switched' from a positive to
      negative EGFR phenotype or vice versa. The specificity of EGFR phenotyping by the
      CellSearch system was verified by staining of EGFR only being present in a high
      EGFR expressing EGFR cell line (MDA-MB-468), as confirmed by Western blotting.
      CONCLUSIONS: Measurement of EGFR on the surface of CTCs, derived from individuals
      with metastatic breast cancer patients is possible using the CellSearch system
      and showed consistent positivity over time. The use of this system will now be
      validated in a prospective study aiming to identify patients for anti-EGFR
      therapy based on the expression profile of CTCs.

PMID- 19102717
TI  - Pharmacogenomics of gemcitabine in non-small-cell lung cancer and other solid
      tumors.
AB  - The validation of predictive biomarkers to tailor chemotherapy is a key issue in
      the development of effective treatment modalities against cancer. Examples of how
      genetics might affect drug response are offered by gemcitabine. A substantial
      number of potential biomarkers for sensitivity or resistance to gemcitabine have
      been proposed, including ribonucleotide reductase and cytidine deaminase
      polymorphisms, human equilibrative transporter-1 and ribonucleotide reductase
      gene-expression and AKT phosphorylation status. These markers displayed a
      significant relationship with disease response to the drug; however, their
      robustness needs to be evaluated within prospective studies. Moreover, recent
      trials of customized chemotherapy based on genetic markers have been carried out
      in non-small-cell lung cancer and promising pharmacogenetic determinants are
      gaining momentum, including BRCA1 and ERCC1. Hopefully, biomarkers to select
      patients most likely to respond to gemcitabine will be validated in the near
      future.

PMID- 19102716
TI  - EGFR-targeted therapies in lung cancer: predictors of response and toxicity.
AB  - The EGFR pathway has emerged as a key target in non-small-cell lung cancer. EGF
      receptor (EGFR) inhibition in non-small-cell lung cancer is achieved via small
      molecular tyrosine kinase inhibitors, such as erlotinib or gefitinib, or
      monoclonal antibodies such as cetuximab. A growing body of evidence is
      identifying potential molecular predictors of response and toxicity. This
      includes tumor-related molecular markers, such as EGFR mutation and copy number,
      as well as germline markers such as polymorphisms in EGFR or EGFR pathway-related
      genes. This review focuses on the current state of knowledge of predictors of
      response and toxicity to EGFR inhibitors in lung cancer.

PMID- 19102718
TI  - Predictive role of C677T MTHFR polymorphism in variable efficacy of photodynamic
      therapy for neovascular age-related macular degeneration.
AB  - Age-related macular degeneration (AMD) complicated by subfoveal choroidal
      neovascularization (CNV) is the leading cause of severe central blindness in
      developed countries. AMD-related CNVs are distinguishable in classic and occult
      subtypes, characterized by variable natural history and different responsiveness
      to therapeutic procedures. Combined and repeated use of photodynamic therapy with
      verteporfin (PDT-V) and antiangiogenic drugs represents the most promising
      strategy against neovascular AMD, but it is unavoidably associated with mounting
      health-resource utilization. Predictive correlations between peculiar coagulation
      balance gene variants and different levels of post-PDT-V benefit have recently
      been documented in Caucasians with AMD-related CNVs. In particular,
      methylenetetrahydrofolate reductase C677T substitution, a common thrombophilic
      folate pathway genotypic polymorphism, influences a better CNV responsiveness to
      PDT-V in classic- but not in occult-CNV cases. These pharmacogenetic findings
      indicate the opportunities to optimize the eligibility criteria of PDT-V and/or
      to perform this intriguing therapy in a customized manner, for finally minimizing
      the socio-economic burden of neovascular AMD.

PMID- 19102719
TI  - Pharmacogenomics of IFN-beta in multiple sclerosis: towards a personalized
      medicine approach.
AB  - Multiple sclerosis (MS) is an inflammatory disease of the CNS. The clinical
      presentation of MS is heterogeneous. Interferons (IFNs) were the first agents to
      show clinical efficacy in the treatment of MS and prolonged treatment is still
      the best available therapy. Although IFN treatment ameliorates immune
      dysfunction, the response is partial. Clinical experience indicates that there
      are responders and nonresponders. This distinction suggests that a subset of
      patients are insensitive or resistant to the action of IFN. This implies that
      pharmacodynamic responses may differ between patients, leading to interindividual
      differences in clinical response. Understanding of the factors that underlie the
      therapeutic response is key to the identification of predictive markers. Here, we
      describe novel developments in pharmacogenomics research to improve the
      understanding of the pharmacological effects of IFN therapy, and the
      identification of biomarkers that allow stratification of MS patients for their
      response to IFN-beta. Ultimately, this information will lead to a personalized
      form of medicine, whereby a specific therapy will be applied that is best suited
      to an individual patient.

PMID- 19102720
TI  - 4th US FDA-Drug Information Association pharmacogenomics workshop, held 10-12
      December, 2007.
AB  - The 4th US FDA/Industry workshop, in a series on Pharmacogenomics, was on
      'Biomarkers and Pharmacogenomics in Drug Development and Regulatory Decision
      Making' and was held on December 10-12, 2007 in Bethesda, MD, USA, with clear
      objectives to continue the dialogue that began in 2002 for enabling the use of
      biomarkers and pharmacogenomics in drug development and regulatory decision
      making. This brief commentary will highlight the major topics and outcomes
      discussed at this meeting that was jointly sponsored by the FDA, The
      Pharmacogenomics Working Group (PWG), The Pharmaceutical Research and
      Manufacturers of America (PhRMA), The Biotechnology Industry Organization (BIO)
      and The Drug Information Association (DIA).

PMID- 19102721
TI  - Developing the evidence base for applying pharmacogenomics: proceeds from DIA
      Workshop IV--Breakout Session 1.
AB  - The 4th Drug Information Association Workshop in a series of workshops on
      Pharmacogenomics: 'Biomarkers and Pharmacogenomics in Drug Development and
      Regulatory Decision Making' took place on December 10-12, 2007 in Bethesda, MD,
      USA. A number of breakout sessions were conducted to focus on different aspects
      of the development of biomarkers. Breakout Session 1 considered the evidence base
      for the development of pharmacogenomic markers from both safety and efficacy
      perspectives, with a view to understanding the challenges in the design of
      appropriate clinical studies during drug development. Case studies based on data
      generated during all stages of drug development were used to stimulate discussion
      and refine considerations for what constitutes a sufficient evidence base to
      support the effective use of novel, pharmacogenomic biomarkers. The discussions
      were open and lively, and some broad principles were drawn from the discussion.
      In this article, we summarize the case studies presented and develop key
      discussion points that arose out of the meeting. These case studies help to
      illustrate the current state of the art in the application of pharmacogenomics in
      drug development and the challenges being faced in the development of
      pharmacogenomics from interesting, exploratory associations into predictive
      biomarkers with clinical utility. We hope that this will serve as a stimulus to
      consideration of the critical issues facing the implementation of
      pharmacogenomics into drug development.

PMID- 19102722
TI  - Drug-diagnostic codevelopment strategies: FDA and industry dialog at the 4th
      FDA/DIA/PhRMA/PWG/BIO Pharmacogenomics Workshop.
AB  - The 4th US FDA/Industry Workshop on Pharmacogenomics in Drug Development and
      Regulatory Decision Making, was held in MD, USA, on December 10-12, 2007. One of
      the breakout sessions of the workshop focused on the regulatory issues around
      codevelopment of drugs and companion diagnostics. This session used hypothetical
      case studies as focal points for discussion of current thought and critical
      issues for both industry and the FDA in this evolving field. The panel and the
      audience discussed the evolution of the FDA's thinking on the regulatory path for
      companion diagnostics since the release of the April 2005 draft Drug Test
      Codevelopment Concept Paper and the issues faced by industry in attempting
      codevelopment efforts. This session provided an opportunity to allow an exchange
      of ideas between the FDA and industry and to identify critical issues that need
      further discussion in this important and evolving field.

PMID- 19102723
TI  - Fit-for-purpose pharmacogenomic biomarkers in drug development: a project team
      case study with 'what-ifs'.
AB  - Over the past four years, the annual US FDA-DIA pharmacogenomic workshops have
      brought together attendees with wide-ranging expertise spanning industry,
      regulatory authorities and academia. This special report summarizes a breakout
      session using a novel, interactive case format as a way to engage participants,
      raise awareness and share diverse learnings via 'real life' decisions that
      project teams might face in developing a new medicine. This case was situated
      just prior to approval by a Regulatory Authority as a project team is finalizing
      a new medicine label. To effectively integrate new biomarkers such as
      pharmacogenomics into developing new medicines, this session highlighted the
      importance in considering medical practice implications as relevant (or not) to
      information or actions by a prescriber; progressing validation beyond assay to
      clinical; and fitting pharmacogenomics into context with other evidence often
      built over decades during a drug's development. All converge onto a label that
      must communicate evidence-based use of a new medicine that is effective and safe.

PMID- 19102724
TI  - Payer perspectives on pharmacogenomics testing and drug development.
AB  - A series of questions about hypothetical drugs and pharmacogenomic tests was
      posed to a panel of representatives from the health plan, government and employer
      sectors in order to elicit suggestions for input on data or study design
      considerations important for coverage determination. The panel suggested seven
      areas for drug developers to strongly consider. These areas were to include
      comparative information on new tests versus usual care, assess the negative
      predictive value of new tests, measure and report on cost offsets, balance
      relative risk improvement with absolute risk, consider the policy implications of
      the products or tests, report percentage responders in addition to group mean
      improvements, and to include specific pharmacogenomic information in US FDA
      approved labels. The panel was generally enthusiastic about the promise of the
      field to improve drug selection or dosing.

PMID- 19102726
TI  - Lysine-specific gingipain promotes lipopolysaccharide- and active-vitamin D3
      induced osteoclast differentiation by degrading osteoprotegerin.
AB  - Porphyromonas gingivalis is one of the major pathogens of periodontitis, a
      condition characterized by excessive alveolar bone resorption by osteoclasts. The
      bacterium produces cysteine proteases called gingipains, which are classified
      according to their cleavage-site specificity into Kgps (lysine-specific
      gingipains) and Rgps (arginine-specific gingipains). In the present study we
      examined the effects of gingipains on osteoclast differentiation. In co-cultures
      of mouse bone-marrow cells and osteoblasts, formation of multinucleated
      osteoclasts induced by 1alpha,25(OH)(2)D(3) (1alpha,25-dihydroxyvitamin D(3)) was
      augmented by Kgp but not by RgpB. A physiological concentration (0.1 nM) of
      1alpha,25(OH)(2)D(3) induced the osteoclast formation in the presence of 100 nM
      Kgp to an extent comparable with that induced by 10 nM 1alpha,25(OH)(2)D(3). Kgp
      also enhanced osteoclastogenesis induced by various microbial components,
      including lipopolysaccharide. Combined use of Kgp and 1alpha,25(OH)(2)D(3) or
      lipopolysaccharide also increased the number of resorption pits developed on
      dentin slices, indicating that the osteoclasts formed in the presence of Kgp
      possess bone-resorbing activity. The enhanced osteoclastogenesis by Kgp was
      correlated with a depletion of osteoprotegerin in co-culture medium and was
      proteolytic-activity-dependent, since benzyloxycarbonyl-L-phenylalanyl-L
      lysylacycloxyketone, an inhibitor of Kgp, completely abolished osteoclastogenesis
      induced by Kgp. Kgp digested osteoprotegerin, since its recombinant protein was
      susceptible to degradation by Kgp in the presence of serum. As a result, Kgp did
      not augment osteoclastogenesis in co-cultures of osteoprotegerin-deficient
      osteoblasts and bone-marrow cells. In addition, enhanced osteoclastogenesis by
      Kgp was abolished by an excess amount of recombinant osteoprotegerin. These
      findings suggest that degradation of osteoprotegerin is one of the mechanisms
      underlying promotion of osteoclastogenesis by Kgp.

PMID- 19102727
TI  - Characterization of key residues and membrane association domains in retinol
      dehydrogenase 10.
AB  - RDH10 (retinol dehydrogenase 10) was originally identified from the retinal
      pigment epithelium and retinal Muller cells. It has retinoid oxidoreductase
      activity and is thought to play a role in the retinoid visual cycle. A recent
      study showed that RDH10 is essential for generating retinoic acid at early
      embryonic stages. The present study demonstrated that wild-type RDH10 catalysed
      both oxidation of all-trans-retinol and reduction of all-trans-retinal in a
      cofactor-dependent manner In vitro. In cultured cells, however, oxidation is the
      favoured reaction catalysed by RDH10. Substitution of any of the predicted key
      residues in the catalytic centre conserved in the RDH family abolished the
      enzymatic activity of RDH10 without affecting its protein level. Unlike other RDH
      members, however, replacement of Ser(197), a key residue for stabilizing the
      substrate, by glycine and alanine did not abolish the enzymatic activity of
      RDH10, whereas RDH10 mutants S197C, S197T and S197V completely lost their
      enzymatic activity. These results suggest that the size of the residue at
      position 197 is critical for the activity of RDH10. Mutations of the three
      glycine residues (Gly(43), Gly(47) and Gly(49)) in the predicted cofactor-binding
      motif (Gly-Xaa(3)-Gly-Xaa-Gly) of RDH10 abolished its enzymatic activity,
      suggesting that the cofactor-binding motif is essential for its activity.
      Deletion of the two hydrophobic domains dissociated RDH10 from the membrane and
      abolished its activity. These studies identified the key residues for the
      activity of RDH10 and will contribute to the further elucidation of mechanism of
      this important enzyme.

PMID- 19102728
TI  - Single-Myb-histone proteins from Arabidopsis thaliana: a quantitative study of
      telomere-binding specificity and kinetics.
AB  - Proteins that bind telomeric DNA modulate the structure of chromosome ends and
      control telomere function and maintenance. It has been shown that AtTRB
      (Arabidopsis thaliana telomere-repeat-binding factor) proteins from the SMH
      (single-Myb-histone) family selectively bind double-stranded telomeric DNA and
      interact with the telomeric protein AtPOT1b (A. thaliana protection of telomeres
      1b), which is involved in telomere capping. In the present study, we performed
      the first quantitative DNA-binding study of this plant-specific family of
      proteins. Interactions of full-length proteins AtTRB1 and AtTRB3 with telomeric
      DNA were analysed by electrophoretic mobility-shift assay, fluorescence
      anisotropy and surface plasmon resonance to reveal their binding stoichiometry
      and kinetics. Kinetic analyses at different salt conditions enabled us to
      estimate the electrostatic component of binding and explain different affinities
      of the two proteins to telomeric DNA. On the basis of available data, a putative
      model explaining the binding stoichiometry and the protein arrangement on
      telomeric DNA is presented.

PMID- 19102729
TI  - Misperceived pre-pregnancy body weight status predicts excessive gestational
      weight gain: findings from a US cohort study.
AB  - BACKGROUND: Excessive gestational weight gain promotes poor maternal and child
      health outcomes. Weight misperception is associated with weight gain in non
      pregnant women, but no data exist during pregnancy. The purpose of this study was
      to examine the association of misperceived pre-pregnancy body weight status with
      excessive gestational weight gain. METHODS: At study enrollment, participants in
      Project Viva reported weight, height, and perceived body weight status by
      questionnaire. Our study sample comprised 1537 women who had either normal or
      overweight/obese pre-pregnancy BMI. We created 2 categories of pre-pregnancy body
      weight status misperception: normal weight women who identified themselves as
      overweight ('overassessors') and overweight/obese women who identified themselves
      as average or underweight ('underassessors'). Women who correctly perceived their
      body weight status were classified as either normal weight or overweight/obese
      accurate assessors. We performed multivariable logistic regression to determine
      the odds of excessive gestational weight gain according to 1990 Institute of
      Medicine guidelines. RESULTS: Of the 1029 women with normal pre-pregnancy BMI,
      898 (87%) accurately perceived and 131 (13%) overassessed their weight status.
      508 women were overweight/obese, of whom 438 (86%) accurately perceived and 70
      (14%) underassessed their pre-pregnancy weight status. By the end of pregnancy,
      823 women (54%) gained excessively. Compared with normal weight accurate
      assessors, the adjusted odds of excessive gestational weight gain was 2.0 (95%
      confidence interval [CI]: 1.3, 3.0) in normal weight overassessors, 2.9 (95% CI:
      2.2, 3.9) in overweight/obese accurate assessors, and 7.6 (95% CI: 3.4, 17.0) in
      overweight/obese underassessors. CONCLUSION: Misperceived pre-pregnancy body
      weight status was associated with excessive gestational weight gain among both
      normal weight and overweight/obese women, with the greatest likelihood of
      excessive gain among overweight/obese underassessors. Future interventions should
      test the potential benefits of correcting misperception to reduce the likelihood
      of excessive gestational weight gain.

PMID- 19102730
TI  - A systematic search for SNPs/haplotypes associated with disease phenotypes using
      a haplotype-based stepwise procedure.
AB  - BACKGROUND: Genotyping technologies enable us to genotype multiple Single
      Nucleotide Polymorphisms (SNPs) within selected genes/regions, providing data for
      haplotype association analysis. While haplotype-based association analysis is
      powerful for detecting untyped causal alleles in linkage-disequilibrium (LD) with
      neighboring SNPs/haplotypes, the inclusion of extraneous SNPs could reduce its
      power by increasing the number of haplotypes with each additional SNP. METHODS:
      Here, we propose a haplotype-based stepwise procedure (HBSP) to eliminate
      extraneous SNPs. To evaluate its properties, we applied HBSP to both simulated
      and real data, generated from a study of genetic associations of the
      bactericidal/permeability-increasing (BPI) gene with pulmonary function in a
      cohort of patients following bone marrow transplantation. RESULTS: Under the null
      hypothesis, use of the HBSP gave results that retained the desired false positive
      error rates when multiple comparisons were considered. Under various alternative
      hypotheses, HBSP had adequate power to detect modest genetic associations in case
      control studies with 500, 1,000 or 2,000 subjects. In the current application,
      HBSP led to the identification of two specific SNPs with a positive validation.
      CONCLUSION: These results demonstrate that HBSP retains the essence of haplotype
      based association analysis while improving analytic power by excluding extraneous
      SNPs. Minimizing the number of SNPs also enables simpler interpretation and more
      cost-effective applications.

PMID- 19102731
TI  - Evolutionary history of the fish genus Astyanax Baird & Girard (1854)
      (Actinopterygii, Characidae) in Mesoamerica reveals multiple morphological
      homoplasies.
AB  - BACKGROUND: Mesoamerica is one of the world's most complex biogeographical
      regions, mostly due to its complex geological history. This complexity has led to
      interesting biogeographical processes that have resulted in the current diversity
      and distribution of fauna in the region. The fish genus Astyanax represents a
      useful model to assess biogeographical hypotheses due to it being one of the most
      diverse and widely distributed freshwater fish species in the New World. We used
      mitochondrial and nuclear DNA to evaluate phylogenetic relationships within the
      genus in Mesoamerica, and to develop historical biogeographical hypotheses to
      explain its current distribution. RESULTS: Analysis of the entire mitochondrial
      cytochrome b (Cytb) gene in 208 individuals from 147 localities and of a subset
      of individuals for three mitochondrial genes (Cytb, 16 S, and COI) and a single
      nuclear gene (RAG1) yielded similar topologies, recovering six major groups with
      significant phylogeographic structure. Populations from North America and Upper
      Central America formed a monophyletic group, while Middle Central America showed
      evidence of rapid radiation with incompletely resolved relationships. Lower
      Central America lineages showed a fragmented structure, with geographically
      restricted taxa showing high levels of molecular divergence. All Bramocharax
      samples grouped with their sympatric Astyanax lineages (in some cases even with
      allopatric Astyanax populations), with less than 1% divergence between them.
      These results suggest a homoplasic nature to the trophic specializations
      associated with Bramocharax ecomorphs, which seem to have arisen independently in
      different Astyanax lineages. We observed higher taxonomic diversity compared to
      previous phylogenetic studies of the Astyanax genus. Colonization of Mesoamerica
      by Astyanax before the final closure of the Isthmus of Panama (3.3 Mya) explains
      the deep level of divergence detected in Lower Central America. The colonization
      of Upper Mesoamerica apparently occurred by two independent routes, with lineage
      turnover over a large part of the region. CONCLUSION: Our results support
      multiple, independent origins of morphological traits in Astyanax, whereby the
      morphotype associated with Bramocharax represents a recurrent trophic adaptation.
      Molecular clock estimates indicate that Astyanax was present in Mesoamerica
      during the Miocene (approximately 8 Mya), which implies the existence of an
      incipient land-bridge connecting South America and Central America before the
      final closure of the Isthmus of Panama (approximately 3.3 Mya).

PMID- 19102732
TI  - An intronic alteration of the fibroblast growth factor 10 gene causing ALSG
      (aplasia of lacrimal and salivary glands) syndrome.
AB  - BACKGROUND: A combined aplasia, hypoplasia or atresia of lacrimal points and
      salivary glands is rarely diagnosed. Those patients suffer from epiphora,
      xerostomia and severe dental caries. This phenotype represents the autosomal
      dominant aplasia of lacrimal and salivary glands syndrome (ALSG). Recently,
      aberrations of the Fibroblast Growth Factor 10 (FGF10) gene have been identified
      to be causative for this disorder. METHODS: We performed a sequence analysis of
      the FGF10 gene of a patient with ALSG-syndrome and his also affected brother as
      well as 193 controls. The FGF10 transcript was analyzed using RNA extracted from
      primary fibroblasts of the patient's mucosa. RESULTS: We detected a novel
      heterozygous sequence variation in intron 2 (c.430-1, G > A) causing the ALSG
      syndrome. The alteration derogates the regular splice acceptor site and leads to
      the use of a new splice acceptor site 127 bp upstream of exon 3. The aberration
      was detected in the genomic DNA derived from two affected brothers, but not in
      193 control individuals. Furthermore, no diseased member of the family displayed
      additional abnormalities that are indicative for the clinically overlapping
      lacrimo-auriculo-dento-digital syndrome (LADD). CONCLUSION: This family-based
      approach revealed an intronic variation of the FGF10 gene causing ALSG-syndrome.
      Our results expand the mutational and clinical spectrum of the ALSG syndrome.

PMID- 19102733
TI  - Is intracranial atherosclerosis an independent risk factor for cerebral atrophy?
      A retrospective evaluation.
AB  - BACKGROUND: Our purpose was to study the association between the intracranial
      atherosclerosis as measured by cavernous carotid artery calcification (ICAC)
      observed on head CT and atrophic changes of supra-tentorial brain demonstrated by
      MRI. METHODS: Institutional review board approval was obtained for this
      retrospective study incorporating 65 consecutive patients presenting acutely who
      had both head CT and MRI. Arterial calcifications of the intracranial cavernous
      carotids (ICAC) were assigned a number (1 to 4) in the bone window images from CT
      scans. These 4 groups were then combined into high (grades 3 and 4) and low
      calcium (grades 1 and 2) subgroups. Brain MRI was independently evaluated to
      identify cortical and central atrophy. Demographics and cardiovascular risk
      factors were evaluated in subjects with high and low ICAC. Relationship between
      CT demonstrated ICAC and brain atrophy patterns were evaluated both without and
      with adjustment for cerebral ischemic scores and cardiovascular risk factors.
      RESULTS: Forty-six of the 65 (71%) patients had high ICAC on head CT. Subjects
      with high ICAC were older, and had higher prevalence of hypertension, diabetes,
      coronary artery disease (CAD), atrial fibrillation and history of previous stroke
      (CVA) compared to those with low ICAC. Age demonstrated strong correlation with
      both supratentorial atrophy patterns. There was no correlation between ICAC and
      cortical atrophy. There was correlation however between central atrophy and ICAC.
      This persisted even after adjustment for age. CONCLUSION: Age is the most
      important determinant of atrophic cerebral changes. However, high ICAC
      demonstrated age independent association with central atrophy.

PMID- 19102734
TI  - The effect of antipsychotic medication on sexual function and serum prolactin
      levels in community-treated schizophrenic patients: results from the
      Schizophrenia Trial of Aripiprazole (STAR) study (NCT00237913).
AB  - BACKGROUND: The aim of this paper is to evaluate the effect of antipsychotics for
      the treatment of schizophrenia in a community based study on sexual function and
      prolactin levels comparing the use of aripiprazole and standard of care (SOC),
      which was a limited choice of three widely used and available antipsychotics
      (olanzapine, quetiapine or risperidone) (The Schizophrenia Trial of Aripiprazole
      [STAR] study [NCT00237913]). METHOD: This open-label, 26-week, multi-centre,
      randomised study compared aripiprazole to SOC (olanzapine, quetiapine or
      risperidone) in patients with schizophrenia (DSM-IV-TR criteria). The primary
      effectiveness variable was the mean total score of the Investigator Assessment
      Questionnaire (IAQ) at Week 26. The outcome research variables included the
      Arizona Sexual Experience scale (ASEX). This along with the data collected on
      serum prolactin levels at week 4, 8, 12, 18 and 26 will be the focus of this
      paper. RESULTS: A total of 555 patients were randomised to receive aripiprazole
      (n = 284) or SOC (n = 271). Both treatment groups experienced improvements in
      sexual function from baseline ASEX assessments. However at 8 weeks the
      aripiprazole treatment group reported significantly greater improvement compared
      with the SOC group (p = 0.007; OC). Although baseline mean serum prolactin levels
      were similar in the two treatment groups (43.4 mg/dL in the aripiprazole group
      and 42.3 mg/dL in the SOC group, p = NS) at Week 26 OC, mean decreases in serum
      prolactin were 34.2 mg/dL in the aripiprazole group, compared with 13.3 mg/dL in
      the SOC group (p < 0.001). CONCLUSION: The study findings suggest that
      aripiprazole has the potential to reduce sexual dysfunction, which in turn might
      improve patient compliance.

PMID- 19102735
TI  - Responses to language barriers in consultations with refugees and asylum seekers:
      a telephone survey of Irish general practitioners.
AB  - BACKGROUND: Refugees and asylum seekers experience language barriers in general
      practice. Qualitative studies have found that responses to language barriers in
      general practice are ad hoc with use of both professional interpreters and
      informal interpreters (patients' relatives or friends). However, the scale of the
      issues involved is unknown. This study quantifies the need for language
      assistance in general practice consultations and examines the experience of, and
      satisfaction with, methods of language assistance utilized. METHODS: Data were
      collected by telephone survey with general practitioners in a regional health
      authority in Ireland between July-August 2004. Each respondent was asked a series
      of questions about consulting with refugees and asylum seekers, the need for
      language assistance and the kind of language assistance used. RESULTS: There was
      a 70% (n = 56/80) response rate to the telephone survey. The majority of
      respondents (77%) said that they had experienced consultations with refugees and
      asylum seekers in which language assistance was required. Despite this, general
      practitioners in the majority of cases managed without an interpreter or used
      informal methods of interpretation. In fact, when given a choice general
      practitioners would more often choose informal over professional methods of
      interpretation despite the fact that confidentiality was a significant concern.
      CONCLUSION: The need for language assistance in consultations with refugees and
      asylum seekers in Irish general practice is high. General practitioners rely on
      informal responses. It is necessary to improve knowledge about the organisational
      contexts that shape general practitioners responses. We also recommend dialogue
      between general practitioners, patients and interpreters about the relative
      merits of informal and professional methods of interpretation so that general
      practitioners' choices are responsive to the needs of patients with limited
      English.

PMID- 19102736
TI  - Prediction of protein-protein binding site by using core interface residue and
      support vector machine.
AB  - BACKGROUND: The prediction of protein-protein binding site can provide structural
      annotation to the protein interaction data from proteomics studies. This is very
      important for the biological application of the protein interaction data that is
      increasing rapidly. Moreover, methods for predicting protein interaction sites
      can also provide crucial information for improving the speed and accuracy of
      protein docking methods. RESULTS: In this work, we describe a binding site
      prediction method by designing a new residue neighbour profile and by selecting
      only the core-interface residues for SVM training. The residue neighbour profile
      includes both the sequential and the spatial neighbour residues of an interface
      residue, which is a more complete description of the physical and chemical
      characteristics surrounding the interface residue. The concept of core interface
      is applied in selecting the interface residues for training the SVM models, which
      is shown to result in better discrimination between the core interface and other
      residues. The best SVM model trained was tested on a test set of 50 randomly
      selected proteins. The sensitivity, specificity, and MCC for the prediction of
      the core interface residues were 60.6%, 53.4%, and 0.243, respectively. Our
      prediction results on this test set were compared with other three binding site
      prediction methods and found to perform better. Furthermore, our method was
      tested on the 101 unbound proteins from the protein-protein interaction benchmark
      v2.0. The sensitivity, specificity, and MCC of this test were 57.5%, 32.5%, and
      0.168, respectively. CONCLUSION: By improving both the descriptions of the
      interface residues and their surrounding environment and the training strategy,
      better SVM models were obtained and shown to outperform previous methods. Our
      tests on the unbound protein structures suggest further improvement is possible.

PMID- 19102737
TI  - Physical activity and persistent low back pain and pelvic pain post partum.
AB  - BACKGROUND: The aims of this study were (i) to investigate the potential
      influence of pre-pregnancy regular leisure-time physical activity (PA) on the
      risk of persistent LBPP half a year after pregnancy, and (ii) to explore the
      starting time and prevalence of PA among women experiencing LBPP during
      pregnancy, in relation to remission or persistent LBPP half a year after
      pregnancy. METHODS: This study is a follow-up study of 639 women who reported
      LBPP during pregnancy. These women were sent a questionnaire at approximately six
      months after delivery. The respondents were divided into three groups: 'no pain',
      'recurrent pain', and 'continuous pain'. Data were analysed using an independent
      samples t-test, Pearson's chi-squared test, and univariate and multivariate
      logistic regression analyses. RESULTS: 44.5% of subjects reported current PA at
      six months post partum. The mean starting time of PA was 2.6 months post partum
      and the mean number of current, weekly events of PA was 3.4; there were no
      differences between the groups. 82.2% reported previous PA at some period in
      life. Women with BMI >/= 30 reported current PA to a lesser extent. The number of
      years of pre-pregnancy PA did not influence the risk of persistent LBPP.
      CONCLUSION: Almost half of women who had experienced LBPP during pregnancy
      reported PA at six months post partum. The number of years of pre-pregnancy PA
      did not influence the risk of persistent LBPP. Obesity was a risk factor for not
      practising PA.

PMID- 19102738
TI  - Prevalence and characteristics of epilepsy in the Belgian shepherd variants
      Groenendael and Tervueren born in Denmark 1995-2004.
AB  - BACKGROUND: The Belgian shepherd Groenendael and Tervueren is believed to be at
      higher risk of developing epilepsy than dogs of the common population. This
      epidemiological study was designed to estimate the prevalence of epilepsy in the
      Danish population of Groenendael and Tervueren born between 1995 and 2004.
      Furthermore, it was the intention to describe the clinical manifestation (seizure
      types and phenomenology) of epilepsy and to identify risk factors for euthanasia
      once the dog was diagnosed as having epilepsy. METHODS: All owners of Groenendael
      and Tervueren dogs born between January 1995 and December 2004 and registered in
      the Danish Kennel Club (1,248 dogs) were contacted and asked to answer a mailed
      questionnaire concerning epilepsy. Positive responders were subsequently
      validated in a follow-up interview conducted by telephone using a standardized
      questionnaire. Owners were questioned about age at first seizure, seizure
      frequency, seizure duration, a detailed description of seizure phenomenology,
      post-ictal signs and if a veterinarian had diagnosed the dog with epilepsy.
      RESULTS: Prevalence of epilepsy was estimated at 9.5%. Mean age of epilepsy debut
      was 3.3 years (range 0.5-8.0 years). There was an almost equal number of
      Groenendael (25) and Tervueren (24). The distribution of females and males was 31
      and 18 respectively. Twenty-five per cent experienced focal seizures, 53%
      experienced focal seizures with secondary generalization and 18% experienced
      primary generalized seizures. In four percent seizures were unclassifiable. The
      most commonly reported focal seizure phenomenology included ataxia, crawling,
      swaying, fearful behavior, salivation, excessive attention seeking and
      disorientation. In 16% of the cases, epilepsy led to euthanasia. Intact dogs with
      epilepsy had a significantly increased risk of being euthanized because of
      epilepsy compared to neutered dogs with epilepsy. In 22% of the cases the owners
      reported that anxiety/hyperactivity/stress could act as a seizure provoking
      factor. CONCLUSION: A high prevalence of epilepsy appears to be present in the
      Danish Groenendael and Tervueren population. The relatively late debut age of
      epilepsy in this breed contributes greatly to the increased prevalence of
      epileptic individuals, because dogs developing epilepsy late in life are used for
      breeding unintended.

PMID- 19102739
TI  - Ipsilateral common iliac artery plus femoral artery clamping for inducing sciatic
      nerve ischemia/reperfusion injury in rats: a reliable and simple method.
AB  - The aim of this study was to develop a practical model of sciatic ischemia
      reperfusion (I/R) injury producing serious neurologic deficits and being
      technically feasible compared with the current time consuming or ineffective
      models. Thirty rats were divided into 6 groups (n = 5). Animal were anesthetized
      by using ketamine (50 mg/kg) and xylazine (4 mg/kg). Experimental groups included
      a sham-operated group and five I/R groups with different reperfusion time
      intervals (0 h, 3 h, 1 d, 4 d, 7 d). In I/R groups, the right common iliac artery
      and the right femoral artery were clamped for 3 hrs. Sham-operated animals
      underwent only laparotomy without induction of ischemia. Just before euthanasia,
      behavioral scores (based on gait, grasp, paw position, and pinch sensitivity)
      were obtained and then sciatic nerves were removed for light-microscopy studies
      (for ischemic fiber degeneration (IFD) and edema). Behavioral score deteriorated
      among the ischemic groups compared with the control group (p < 0.01), with
      maximal behavioral deficit occurring at 4 days of reperfusion. Axonal swelling
      and IFD were found to happen only after 4 and 7 days, respectively. Our
      observations led to an easy-to-use but strong enough method for inducing and
      studying I/R injury in peripheral nerves.

PMID- 19102740
TI  - Towards comprehensive assessment of mitral regurgitation using cardiovascular
      magnetic resonance.
AB  - Cardiovascular magnetic resonance (CMR) is increasingly used to assess patients
      with mitral regurgitation. Its advantages include quantitative determination of
      ventricular volumes and function and the mitral regurgitant fraction, and in
      ischemic mitral regurgitation, regional myocardial function and viability. In
      addition to these, identification of leaflet prolapse or restriction is necessary
      when valve repair is contemplated. We describe a systematic approach to the
      evaluation of mitral regurgitation using CMR which we have used in 149 patients
      with varying etiologies and severity of regurgitation over a 15 month period.
      Following standard ventricular cine acquisitions, including 2, 3 and 4 chamber
      long axis views and a short axis stack for biventricular function, we image
      movements of all parts of the mitral leaflets using a contiguous stack of oblique
      long axis cines aligned orthogonal to the central part of the line of coaptation.
      The 8-10 slices in the stack, orientated approximately parallel to a 3-chamber
      view, are acquired sequentially from the superior (antero-lateral) mitral
      commissure to the inferior (postero-medial) commissure, visualising each apposing
      pair of anterior and posterior leaflet scallops in turn (A1-P1, A2-P2 and A3-P3).
      We use balanced steady state free precession imaging at 1.5 Tesla, slice
      thickness 5 mm, with no inter-slice gaps. Where the para-commissural coaptation
      lines curve relative to the central region, two further oblique cines are
      acquired orthogonal to the line of coaptation adjacent to each commissure. To
      quantify mitral regurgitation, we use phase contrast velocity mapping to measure
      aortic outflow, subtracting this from the left ventricular stroke volume to
      calculate the mitral regurgitant volume which, when divided by the left
      ventricular stroke volume, gives the mitral regurgitant fraction. In patients
      with ischemic mitral regurgitation, we further assess regional left ventricular
      function and, with late gadolinium enhancement, myocardial viability.
      Comprehensive assessment of mitral regurgitation using CMR is feasible and
      enables determination of mitral regurgitation severity, associated leaflet
      prolapse or restriction, ventricular function and viability in a single
      examination and is now routinely performed at our centre. The mitral valve stack
      of images is particularly useful and easy to acquire.

PMID- 19102741
TI  - Health worker densities and immunization coverage in Turkey: a panel data
      analysis.
AB  - BACKGROUND: Increased immunization coverage is an important step towards
      fulfilling the Millennium Development Goal of reducing childhood mortality.
      Recent cross-sectional and cross-national research has indicated that physician,
      nurse and midwife densities may positively influence immunization coverage.
      However, little is known about relationships between densities of human resources
      for health (HRH) and vaccination coverage within developing countries and over
      time. The present study examines HRH densities and coverage of the Expanded
      Programme on Immunization (EPI) in Turkey during the period 2000 to 2006.
      METHODS: The study is based on provincial-level data on HRH densities,
      vaccination coverage and provincial socioeconomic and demographic characteristics
      published by the Turkish government. Panel data regression methodologies (random
      and fixed effects models) are used to analyse the data. RESULTS: Three main
      findings emerge: (1) combined physician, nurse/midwife and health officer density
      is significantly associated with vaccination rates--independent of provincial
      female illiteracy, GDP per capita and land area--although the association was
      initially positive and turned negative over time; (2) HRH-vaccination rate
      relationships differ by cadre of health worker, with physician and health
      officers exhibiting significant relationships that mirror those for aggregate
      density, while nurse/midwife densities are not consistently significant; (3) HRH
      densities bear stronger relationships with vaccination coverage among more rural
      provinces, compared to those with higher population densities. CONCLUSION: We
      find evidence of relationships between HRH densities and vaccination rates even
      at Turkey's relatively elevated levels of each. At the same time, variations in
      results between different empirical models suggest that this relationship is
      complex, affected by other factors that occurred during the study period, and
      warrants further investigation to verify our findings. We hypothesize that the
      introduction of certain health-sector policies governing terms of HRH employment
      affected incentives to provide vaccinations and therefore relationships between
      HRH densities and vaccination rates. National-level changes experienced during
      the study period--such as a severe financial crisis--may also have affected
      and/or been associated with the HRH-vaccination rate link. While our findings
      therefore suggest that the size of a health workforce may be associated with
      service provision at a relatively elevated level of development, they also
      indicate that focusing on per capita levels of HRH may be of limited value in
      understanding performance in service provision. In both Turkey and elsewhere,
      further investigation is needed to corroborate our results as well as gain deeper
      understanding into relationships between health worker densities and service
      provision.

PMID- 19102742
TI  - Traditional Indian medicine and homeopathy for HIV/AIDS: a review of the
      literature.
AB  - BACKGROUND: Allopathic practitioners in India are outnumbered by practitioners of
      traditional Indian medicine and homeopathy (TIMH), which is used by up to two
      thirds of its population to help meet primary health care needs, particularly in
      rural areas. India has an estimated 2.5 million HIV infected persons. However,
      little is known about TIMH use, safety or efficacy in HIV/AIDS management in
      India, which has one of the largest indigenous medical systems in the world. The
      purpose of this review was to assess the quality of peer-reviewed, published
      literature on TIMH for HIV/AIDS care and treatment. RESULTS: Of 206 original
      articles reviewed, 21 laboratory studies, 17 clinical studies, and 6 previous
      reviews of the literature were identified that covered at least one system of
      TIMH, which includes Ayurveda, Unani medicine, Siddha medicine, homeopathy, yoga
      and naturopathy. Most studies examined either Ayurvedic or homeopathic
      treatments. Only 4 of these studies were randomized controlled trials, and only
      10 were published in MEDLINE-indexed journals. Overall, the studies reported
      positive effects and even "cure" and reversal of HIV infection, but frequent
      methodological flaws call into question their internal and external validity.
      Common reasons for poor quality included small sample sizes, high drop-out rates,
      design flaws such as selection of inappropriate or weak outcome measures, flaws
      in statistical analysis, and reporting flaws such as lack of details on products
      and their standardization, poor or no description of randomization, and
      incomplete reporting of study results. CONCLUSION: This review exposes a broad
      gap between the widespread use of TIMH therapies for HIV/AIDS, and the dearth of
      high-quality data supporting their effectiveness and safety. In light of the
      suboptimal effectiveness of vaccines, barrier methods and behavior change
      strategies for prevention of HIV infection and the cost and side effects of
      antiretroviral therapy (ART) for its treatment, it is both important and urgent
      to develop and implement a rigorous research agenda to investigate the potential
      risks and benefits of TIMH and to identify its role in the management of HIV/AIDS
      and associated illnesses in India.

PMID- 19102743
TI  - In-reach specialist nursing teams for residential care homes: uptake of services,
      impact on care provision and cost-effectiveness.
AB  - BACKGROUND: A joint NHS-Local Authority initiative in England designed to provide
      a dedicated nursing and physiotherapy in-reach team (IRT) to four residential
      care homes has been evaluated. The IRT supported 131 residents and maintained 15
      'virtual' beds for specialist nursing in these care homes. METHODS: Data captured
      prospectively (July 2005 to June 2007) included: numbers of referrals; reason for
      referral; outcome (e.g. admission to IRT bed, short-term IRT support); length of
      stay in IRT; prevented hospital admissions; early hospital discharges; avoided
      nursing home transfers; and detection of unrecognised illnesses. An economic
      analysis was undertaken. RESULTS: 733 referrals were made during the 2 years
      (range 0.5 to 13.0 per resident per annum) resulting in a total of 6,528 visits.
      Two thirds of referrals aimed at maintaining the resident's independence in the
      care home. According to expert panel assessment, 197 hospital admissions were
      averted over the period; 20 early discharges facilitated; and 28 resident
      transfers to a nursing home prevented. Detection of previously unrecognised
      illnesses accounted for a high number of visits. Investment in IRT equalled 44.38
      pounds per resident per week. Savings through reduced hospital admissions, early
      discharges, delayed transfers to nursing homes, and identification of previously
      unrecognised illnesses are conservatively estimated to produce a final reduction
      in care cost of 6.33 pounds per resident per week. A sensitivity analysis
      indicates this figure might range from a weekly overall saving of 36.90 pounds
      per resident to a 'worst case' estimate of 2.70 pounds extra expenditure per
      resident per week.Evaluation early in implementation may underestimate some cost
      saving activities and greater savings may emerge over a longer time period.
      Similarly, IRT costs may reduce over time due to the potential for refinement of
      team without major loss in effectiveness. CONCLUSION: Introduction of a
      specialist nursing in-reach team for residential homes is at least cost neutral
      and, in all probability, cost saving. Further benefits include development of new
      skills in the care home workforce and enhanced quality of care. Residents are
      enabled to stay in familiar surroundings rather than unnecessarily spending time
      in hospital or being transferred to a higher dependency nursing home setting.

PMID- 19102744
TI  - Voxel-based structural magnetic resonance imaging (MRI) study of patients with
      early onset schizophrenia.
AB  - BACKGROUND: Investigation into the whole brain morphology of early onset
      schizophrenia (EOS) to date has been sparse. We studied the regional brain
      volumes in EOS patients, and the correlations between regional volume measures
      and symptom severity. METHODS: A total of 18 EOS patients (onset under 16 years)
      and 18 controls matched for age, gender, parental socioeconomic status, and
      height were examined. Voxel-based morphometric analysis using the Brain Analysis
      Morphological Mapping (BAMM) software package was employed to explore alterations
      of the regional grey (GM) and white matter (WM) volumes in EOS patients. Symptoms
      were assessed using the Positive and Negative Syndrome Scale (PANSS). RESULTS:
      EOS patients had significantly reduced GM volume in the left parahippocampal,
      inferior frontal, and superior temporal gyri, compared with the controls. They
      also had less WM volume in the left posterior limb of the internal capsule and
      the left inferior longitudinal fasciculus. The positive symptom score of PANSS
      (higher values corresponding to more severe symptoms) was negatively related to
      GM volume in the bilateral posterior cingulate gyrus. The negative symptom score
      was positively correlated with GM volume in the right thalamus. As for the
      association with WM volume, the positive symptom score of PANSS was positively
      related to cerebellar WM (vermis region), and negatively correlated with WM in
      the brain stem (pons) and in the bilateral cerebellum (hemisphere region).
      CONCLUSION: Our findings of regional volume alterations of GM and WM in EOS
      patients coincide with those of previous studies of adult onset schizophrenia
      patients. However, in brain regions that had no overall structural differences
      between EOS patients and controls (that is, the bilateral posterior cingulate
      gyrus, the right thalamus, the cerebellum, and the pons), within-subject analysis
      of EOS patients alone revealed that there were significant associations of the
      volume in these areas and the symptom severity. These findings suggest that at an
      early stage of the illness, especially for those with onset before brain
      maturation, a wide range of disturbed neural circuits, including these brain
      regions that show no apparent morphological changes, may contribute to the
      formation of the symptomatology.

PMID- 19102745
TI  - Synergistic effect of methyljasmonate and cyclodextrin on stilbene biosynthesis
      pathway gene expression and resveratrol production in Monastrell grapevine cell
      cultures.
AB  - BACKGROUND: Plant cell cultures have been shown as feasible systems for the
      production of secondary metabolites, being the elicitation with biotic or abiotic
      stimuli the most efficient strategy to increase the production of those
      metabolites. Vitaceae phytoalexins constitute a group of molecules belonging to
      the stilbene family which are derivatives of the trans-resveratrol structure and
      are produced by plants and cell cultures as a response to biotic and abiotic
      stresses. The potential benefits of resveratrol on human health have made it one
      of the most thoroughly studied phytochemical molecules. The aim of this study was
      to evaluate the elicitor effect of both cyclodextrin (CD) and methyljasmonate
      (MeJA) on grapevine cell cultures by carrying out a quantitative analysis of
      their role on resveratrol production and on the expression of stilbene
      biosynthetic genes in Vitis vinifera cv Monastrell albino cell suspension
      cultures. FINDINGS: MeJA and CD significantly but transiently induced the
      expression of stilbene biosynthetic genes when independently used to treat
      grapevine cells. This expression correlated with resveratrol production in CD
      treated cells but not in MeJA-treated cells, which growth was drastically
      affected. In the combined treatment of CD and MeJA cell growth was similarly
      affected, however resveratrol production was almost one order of magnitude
      higher, in correlation with maximum expression values for stilbene biosynthetic
      genes. CONCLUSION: The effect of MeJA on cell division combined with a true and
      strong elicitor like CD could be responsible for the observed synergistic effect
      of both compounds on resveratrol production and on the expression of genes in the
      stilbene pathway.

PMID- 19102746
TI  - A randomized, open-label, comparative efficacy trial of artemether-lumefantrine
      suspension versus artemether-lumefantrine tablets for treatment of uncomplicated
      Plasmodium falciparum malaria in children in western Kenya.
AB  - BACKGROUND: Artemether/lumefantrine (AL) has been adopted as the treatment of
      choice for uncomplicated malaria in Kenya and other countries in the region. Six
      dose artemether/lumefantrine tablets are highly effective and safe for the
      treatment of infants and children weighing between five and 25 kg with
      uncomplicated Plasmodium falciparum malaria. However, oral paediatric
      formulations are urgently needed, as the tablets are difficult to administer to
      young children, who cannot swallow whole tablets or tolerate the bitter taste of
      the crushed tablets. METHODS: A randomized, controlled, open-label trial was
      conducted comparing day 28 PCR corrected cure-rates in 245 children aged 6-59
      months, treated over three days with either six-dose of artemether/lumefantrine
      tablets (Coartem) or three-dose of artemether/lumefantrine suspension (Co
      artesiane) for uncomplicated falciparum malaria in western Kenya. The children
      were followed-up with clinical, parasitological and haematological evaluations
      over 28 days. RESULTS: Ninety three percent (124/133) and 90% (121/134) children
      in the AL tablets and AL suspension arms respectively completed followed up. A
      per protocol analysis revealed a PCR-corrected parasitological cure rate of 96.0%
      at Day 28 in the AL tablets group and 93.4% in the AL suspension group, p = 0.40.
      Both drugs effectively cleared gametocytes and were well tolerated, with no
      difference in the overall incidence of adverse events. CONCLUSION: The once daily
      three-dose of artemether-lumefantrine suspension (Co-artesiane(R)) was not
      superior to six-dose artemether-lumefantrine tablets (Coartem) for the treatment
      of uncomplicated malaria in children below five years of age in western Kenya.

PMID- 19102747
TI  - Novel measures of cardiovascular health and its association with prevalence and
      progression of age-related macular degeneration: the CHARM Study.
AB  - BACKGROUND: To determine if novel measures of cardiovascular health are
      associated with prevalence or progression of age-related macular degeneration
      (AMD). METHODS: Measures of the cardiovascular system: included intima media
      thickness (IMT), pulse wave velocity (PWV), systemic arterial compliance (SAC),
      carotid augmentation index (AI). For the prevalence study, hospital-based AMD
      cases and population-based age- and gender-matched controls with no signs of AMD
      in either eye were enrolled. For the progression component, participants with
      early AMD were recruited from two previous studies; cases were defined as
      progression in one or both eyes and controls were defined as no progression in
      either eye. RESULTS: 160 cases and 160 controls were included in the prevalence
      component. The upper two quartiles of SAC, implying good cardiovascular health,
      were significantly associated with increased risk of AMD (OR = 2.54, 95% CL =
      1.29, 4.99). High PWV was associated with increased prevalent AMD. Progression
      was observed in 82 (32.3%) of the 254 subjects recruited for the progression
      component. Higher AI (worse cardiovascular function) was protective for AMD
      progression (OR = 0.30, 95%CL = 0.13, 0.69). Higher aortic PWV was associated
      with increased risk of AMD progression; the highest risk was seen with the second
      lowest velocity (OR = 6.22, 95% CL = 2.35, 16.46). CONCLUSION: The results were
      unexpected in that better cardiovascular health was associated with increased
      risk of prevalent AMD and progression. Inconsistent findings between the
      prevalence and progression components could be due to truly different disease
      etiologies or to spurious findings, as can occur with inherent biases in case
      control studies of prevalence. Further investigation of these non-invasive
      methods of characterizing the cardiovascular system should be undertaken as they
      may help to further elucidate the role of the cardiovascular system in the
      etiology of prevalent AMD and progression.

PMID- 19102748
TI  - Selection of internal control genes for quantitative real-time RT-PCR studies
      during tomato development process.
AB  - BACKGROUND: The elucidation of gene expression patterns leads to a better
      understanding of biological processes. Real-time quantitative RT-PCR has become
      the standard method for in-depth studies of gene expression. A biologically
      meaningful reporting of target mRNA quantities requires accurate and reliable
      normalization in order to identify real gene-specific variation. The purpose of
      normalization is to control several variables such as different amounts and
      quality of starting material, variable enzymatic efficiencies of
      retrotranscription from RNA to cDNA, or differences between tissues or cells in
      overall transcriptional activity. The validity of a housekeeping gene as
      endogenous control relies on the stability of its expression level across the
      sample panel being analysed. In the present report we describe the first
      systematic evaluation of potential internal controls during tomato development
      process to identify which are the most reliable for transcript quantification by
      real-time RT-PCR. RESULTS: In this study, we assess the expression stability of 7
      traditional and 4 novel housekeeping genes in a set of 27 samples representing
      different tissues and organs of tomato plants at different developmental stages.
      First, we designed, tested and optimized amplification primers for real-time RT
      PCR. Then, expression data from each candidate gene were evaluated with three
      complementary approaches based on different statistical procedures. Our analysis
      suggests that SGN-U314153 (CAC), SGN-U321250 (TIP41), SGN-U346908 ("Expressed")
      and SGN-U316474 (SAND) genes provide superior transcript normalization in tomato
      development studies. We recommend different combinations of these exceptionally
      stable housekeeping genes for suited normalization of different developmental
      series, including the complete tomato development process. CONCLUSION: This work
      constitutes the first effort for the selection of optimal endogenous controls for
      quantitative real-time RT-PCR studies of gene expression during tomato
      development process. From our study a tool-kit of control genes emerges that
      outperform the traditional genes in terms of expression stability.

PMID- 19102750
TI  - Progressive acetabular dysplasia in a boy with mucopolysaccharoidosis type IV A
      (Morquio syndrome): a case report.
AB  - BACKGROUND: Morquio syndrome is an autosomal recessive lysosomal storage
      disorder, a mucopolysaccharidosis (PMS), characterized by abnormal metabolism of
      glycosaminoglycans. Major treatable concerns in patients with MPS type IV involve
      C1 to C2 instability, genu valgum, and hip subluxation. All patients demonstrate
      characteristic acetabular dysplasia and failure of ossification of the
      superolateral femoral head. CASE PRESENTATION: We report on a 6-year-old boy
      whose prime presentation was a waddling gait associated with pain since early
      childhood. Radiographic documentation showed progressive acetabulo-femoral
      dysplasia associated with additional skeletal deformities. Laboratory
      investigations showed increased urinary keratan sulfate and reduced leukocyte
      enzymatic activity of N-Acetyl-Galaktosamin-6-sulfate-sulfatase.
      Mucopolysaccharoidosis type IV A (Morquio syndrome) has been identified.
      CONCLUSION: Patients with Morquio syndrome usually appear normal at birth but
      exhibit growth failure and spondyloepiphyseal dysplasia as infants. Most children
      are brought to a physician for investigation of what the parents perceive as an
      abnormal appearance by 12 to 18 months of age and thoracic kyphosis is supposed
      to be the first appearing deformity. In our present patient progressive
      acetabular dysplasia was the prime orthopaedic presentation causing effectively
      the development of a painful waddling gait.

PMID- 19102749
TI  - Pleiotropic effects in Eya3 knockout mice.
AB  - BACKGROUND: In Drosophila, mutations in the gene eyes absent (eya) lead to severe
      defects in eye development. The functions of its mammalian orthologs Eya1-4 are
      only partially understood and no mouse model exists for Eya3. Therefore, we
      characterized the phenotype of a new Eya3 knockout mouse mutant. RESULTS:
      Expression analysis of Eya3 by in-situ hybridizations and beta-Gal-staining of
      Eya3 mutant mice revealed abundant expression of the gene throughout development,
      e.g. in brain, eyes, heart, somites and limbs suggesting pleiotropic effects of
      the mutated gene. A similar complex expression pattern was observed also in
      zebrafish embryos. The phenotype of young adult Eya3 mouse mutants was
      systematically analyzed within the German Mouse Clinic. There was no obvious
      defect in the eyes, ears and kidneys of Eya3 mutant mice. Homozygous mutants
      displayed decreased bone mineral content and shorter body length. In the lung,
      the tidal volume at rest was decreased, and electrocardiography showed increased
      JT- and PQ intervals as well as decreased QRS amplitude. Behavioral analysis of
      the mutants demonstrated a mild increase in exploratory behavior, but decreased
      locomotor activity and reduced muscle strength. Analysis of differential gene
      expression revealed 110 regulated genes in heart and brain. Using real-time PCR,
      we confirmed Nup155 being down regulated in both organs. CONCLUSION: The loss of
      Eya3 in the mouse has no apparent effect on eye development. The wide-spread
      expression of Eya3 in mouse and zebrafish embryos is in contrast to the
      restricted expression pattern in Xenopus embryos. The loss of Eya3 in mice leads
      to a broad spectrum of minor physiological changes. Among them, the mutant mice
      move less than the wild-type mice and, together with the effects on respiratory,
      muscle and heart function, the mutation might lead to more severe effects when
      the mice become older. Therefore, future investigations of Eya3 function should
      focus on aging mice.

PMID- 19102751
TI  - Physical function and self-rated health status as predictors of mortality:
      results from longitudinal analysis in the ilSIRENTE study.
AB  - BACKGROUND: Physical function measures have been shown to predict negative health
      related events in older persons, including mortality. These markers of
      functioning may interact with the self-rated health (SRH) in the prediction of
      events. Aim of the present study is to compare the predictive value for mortality
      of measures of physical function and SRH status, and test their possible
      interactions. METHODS: Data are from 335 older persons aged >or= 80 years (mean
      age 85.6 years) enrolled in the "Invecchiamento e Longevita nel Sirente"
      (ilSIRENTE) study. The predictive values for mortality of 4-meter walk test,
      Short Physical Performance Battery (SPPB), hand grip strength, Activities of
      Daily Living (ADL) scale, Instrumental ADL (IADL) scale, and a SRH scale were
      compared using proportional hazard models. Kaplan-Meier survival curves for
      mortality and Receiver Operating Characteristic (ROC) curve analyses were also
      computed to estimate the predictive value of the independent variables of
      interest for mortality (alone and in combination). RESULTS: During the 24-month
      follow-up (mean 1.8 years), 71 (21.2%) events occurred in the study sample. All
      the tested variables were able to significantly predict mortality. No significant
      interaction was reported between physical function measures and SRH. The SPPB
      score was the strongest predictor of overall mortality after adjustment for
      potential confounders (per SD increase; HR 0.64; 95%CI 0.48-0.86). A similar
      predictive value was showed by the SRH (per SD increase; HR 0.76; 95%CI 0.59
      0.97). The chair stand test was the SPPB subtask showing the highest prognostic
      value. CONCLUSION: All the tested measures are able to predict mortality with
      different extents, but strongest results were obtained from the SPPB and the SRH.
      The chair stand test may be as useful as the complete SPPB in estimating the
      mortality risk.

PMID- 19102752
TI  - Evidence and Value: Impact on DEcisionMaking--the EVIDEM framework and potential
      applications.
AB  - BACKGROUND: Healthcare decisionmaking is a complex process relying on disparate
      types of evidence and value judgments. Our objectives for this study were to
      develop a practical framework to facilitate decisionmaking in terms of supporting
      the deliberative process, providing access to evidence, and enhancing the
      communication of decisions. METHODS: Extensive analyses of the literature and of
      documented decisionmaking processes around the globe were performed to explore
      what steps are currently used to make decisions with respect to context (from
      evidence generation to communication of decision) and thought process (conceptual
      components of decisions). Needs and methodologies available to support
      decisionmaking were identified to lay the groundwork for the EVIDEM framework.
      RESULTS: A framework was developed consisting of seven modules that can evolve
      over the life cycle of a healthcare intervention. Components of decision that
      could be quantified, i.e., intrinsic value of a healthcare intervention and
      quality of evidence available, were organized into matrices. A multicriteria
      decision analysis (MCDA) Value Matrix (VM) was developed to include the 15
      quantifiable components that are currently considered in decisionmaking. A
      methodology to synthesize the evidence needed for each component of the VM was
      developed including electronic access to full text source documents. A Quality
      Matrix was designed to quantify three criteria of quality for the 12 types of
      evidence usually required by decisionmakers. An integrated system was developed
      to optimize data analysis, synthesis and validation by experts, compatible with a
      collaborative structure. CONCLUSION: The EVIDEM framework promotes transparent
      and efficient healthcare decisionmaking through systematic assessment and
      dissemination of the evidence and values on which decisions are based. It
      provides a collaborative framework that could connect all stakeholders and serve
      the healthcare community at local, national and international levels by allowing
      sharing of data, resources and values. Validation and further development is
      needed to explore the full potential of this approach.

PMID- 19102754
TI  - Asymmetry in the brain influenced the neurological deficits and infarction volume
      following the middle cerebral artery occlusion in rats.
AB  - BACKGROUND: Paw preference in rats is similar to human handedness, which may
      result from dominant hemisphere of rat brain. However, given that lateralization
      is the uniqueness of the humans, many researchers neglect the differences between
      the left and right hemispheres when selecting the middle cerebral artery
      occlusion (MCAO) in rats. The aim of this study was to evaluate the effect of
      ischemia in the dominant hemisphere on neurobehavioral function and on the
      cerebral infarction volume following MCAO in rats. METHODS: The right-handed male
      Sprague-Dawley rats asserted by the quadrupedal food-reaching test were subjected
      to 2 hours MCA occlusion and then reperfusion. RESULTS: The neurological scores
      were significantly worse in the left MCAO group than that in the right MCAO group
      at 1 h, 24 h, 48 h and 72 h (p <0.05 respectively). There was a trend toward
      better neurobehavioral function recovery in the right MCAO group than in the left
      MCAO group. The total infarct volume in left MCAO was significantly larger than
      that in the right (p < 0.05). CONCLUSION: The neurobehavioral function result and
      the pathological result were consistent with the hypothesis that paw preference
      in rats is similar to human handedness, and suggested that ischemia in dominant
      hemisphere caused more significant neurobehavioral consequence than in another
      hemisphere following MCAO in adult rats. Asymmetry in rat brain should be
      considered other than being neglected in choice of rat MCAO model.

PMID- 19102753
TI  - Improvement in symptoms and pulmonary function of asthmatic patients due to their
      treatment according to the Global Strategy for Asthma Management (GINA).
AB  - BACKGROUND: Global Initiative Strategy for Asthma Management (GINA) is poorly
      applied in undeveloped and developing countries. The current study examined the
      effects of applying GINA guidelines on treatment efficacy in asthmatic patients
      in Iran. METHODS: Twenty four asthmatic patients (usual care group) were treated
      as usual and 26 patients (intervention group) according to the GINA for 2 months.
      Asthma symptom score, asthma severity, frequency of symptoms/week and wheezing
      were recorded at the beginning (first visit), one month after treatment (second
      visit), and at the end of the study (third visit). Pulmonary function tests
      (PFTs) were performed by spirometry, and the patients' use of asthma drugs and
      their symptoms were evaluated, at each visit. RESULTS: Asthma symptoms, frequency
      of symptoms/week, chest wheezing, and PFT values were significantly improved in
      the intervention group at the second and third visits compared to first visit (p
      < 0.001 for all measures). In addition, exercise induced cough and wheeze were
      significant improved in the third visit compared to the second visit in this
      group (p < 0.01 for both measures). In the second and third visits all symptoms
      were significantly lower, and PFT values higher, in the intervention group
      compared to the usual care group (p < 0.005 to p < 0.001). In the usual care
      group, there were only small improvements in some parameters in just the second
      visit (p < 0.01 for all measures). The use of asthma drugs was unchanged in the
      usual care group and significantly reduced in the intervention group (p < 0.01)
      by the end of the study. CONCLUSION: Adoption of GINA guidelines improves asthma
      symptoms and pulmonary function in asthmatic patients in Iran.

PMID- 19102755
TI  - Determinants of infant growth in Eastern Uganda: a community-based cross
      sectional study.
AB  - BACKGROUND: Child under-nutrition is a leading factor underlying child mortality
      and morbidity in Sub-Saharan Africa. Several studies from Uganda have reported
      impaired growth, but there have been few if any community-based infant
      anthropometric studies from Eastern Uganda. The aim of this study was to describe
      current infant growth patterns using WHO Child Growth Standards and to determine
      the extent to which these patterns are associated with infant feeding practices,
      equity dimensions, morbidity and use of primary health care for the infants.
      METHODS: A cross-sectional survey of infant feeding practices, socio-economic
      characteristics and anthropometric measurements was conducted in Mbale District,
      Eastern Uganda in 2003; 723 mother-infant (0-11 months) pairs were analysed.
      Infant anthropometric status was assessed using z-scores for weight-for-length
      (WLZ), length-for-age (LAZ) and weight-for-age (WAZ). Dependent dichotomous
      variables were constructed using WLZ < -2 (wasting) and LAZ < -2 (stunting) as
      cut-off values. A conceptual hierarchical framework was used as the basis for
      controlling for the explanatory factors in multivariate analysis. Household
      wealth was assessed using principal components analysis. RESULTS: The prevalences
      of wasting and stunting were 4.2% and 16.7%, respectively. Diarrhoea during the
      previous 14 days was associated with wasting in the crude analysis, but no
      factors were significantly associated with wasting in the adjusted analysis. The
      adjusted analysis for stunting showed associations with age and gender. Stunting
      was more prevalent among boys than girls, 58.7% versus 41.3%. Having brothers
      and/or sisters was a protective factor against stunting (OR 0.4, 95% CI 0.2-0.8),
      but replacement or mixed feeding was not (OR 2.7, 95% CI 1.0-7.1). Lowest
      household wealth was the most prominent factor associated with stunting with a
      more than three-fold increase in odds ratio (OR 3.5, 95% CI 1.6-7.8). This
      pattern was also seen when the mean LAZ was investigated across household wealth
      categories: the adjusted mean difference between the top and the bottom wealth
      categories was 0.58 z-scores, p < 0.001. Those who had received pre-lacteal feeds
      had lower adjusted mean WLZ than those who had not: difference 0.20 z-scores, p =
      0.023. CONCLUSION: Sub-optimal infant feeding practices after birth, poor
      household wealth, age, gender and family size were associated with growth among
      Ugandan infants.

PMID- 19102756
TI  - Penile Mondor's disease: a case report.
AB  - INTRODUCTION: Thrombosis or thromboflebitis of the superficial dorsal vein of the
      penis, known as penile Mondor's disease was first described by Braun-Falco in
      1955. CASE PRESENTATION: A physically healthy 32-year-old man proceed in our unit
      suffered from a painful swelling, on the dorsal aspect of his penis, being more
      painful during erections. Ultrasonography examination revealed a non-compressible
      portion of superficial dorsal vein as well as the lack of venous flow signals in
      Doppler ultrasonography and the patient was treated conservatively. CONCLUSION:
      Penile Mondor's disease is a rare clinical entity that every urologist should be
      able to recognize. Although it is a benign condition and usually self-limited,
      patients proceed to specialist with considerable psychological stress.

PMID- 19102757
TI  - cAMP-dependent and cholinergic regulation of the electrogenic
      intestinal/pancreatic Na+/HCO3- cotransporter pNBC1 in human embryonic kidney
      (HEK293) cells.
AB  - BACKGROUND: The renal (kNBC1) and intestinal (pNBC1) electrogenic Na+/HCO3-
      cotransporter variants differ in their primary structure, transport direction,
      and response to secretagogues. Previous studies have suggested that regulatory
      differences between the two subtypes can be partially explained by unique
      consensus phosphorylation sites included in the pNBC1, but not the kNBC1
      sequence. After having shown activation of NBC by carbachol and forskolin in
      murine colon, we now investigated these pathways in HEK293 cells transiently
      expressing a GFP-tagged pNBC1 construct. RESULTS: Na+- and HCO3-dependent pHi
      recovery from an acid load (measured with BCECF) was enhanced by 5-fold in GFP
      positive cells compared to the control cells in the presence of CO2/HCO3-.
      Forskolin (10(-5) M) had no effect in untransfected cells, but inhibited the pHi
      recovery in cells expressing pNBC1 by 62%. After preincubation with carbachol
      (10(-4) M), the pHi recovery was enhanced to the same degree both in transfected
      and untransfected cells, indicating activation of endogenous alkalizing ion
      transporters. Acid-activated Na+/HCO3- cotransport via pNBC1 expressed in renal
      cells is thus inhibited by cAMP and not affected by cholinergic stimulation, as
      opposed to the findings in native intestinal tissue. CONCLUSION: Regulation of
      pNBC1 by secretagogues appears to be not solely dependent on its primary
      structure, but also on properties of the cell type in which it is expressed.

PMID- 19102758
TI  - ProfileGrids as a new visual representation of large multiple sequence
      alignments: a case study of the RecA protein family.
AB  - BACKGROUND: Multiple sequence alignments are a fundamental tool for the
      comparative analysis of proteins and nucleic acids. However, large data sets are
      no longer manageable for visualization and investigation using the traditional
      stacked sequence alignment representation. RESULTS: We introduce ProfileGrids
      that represent a multiple sequence alignment as a matrix color-coded according to
      the residue frequency occurring at each column position. JProfileGrid is a Java
      application for computing and analyzing ProfileGrids. A dynamic interaction with
      the alignment information is achieved by changing the ProfileGrid color scheme,
      by extracting sequence subsets at selected residues of interest, and by relating
      alignment information to residue physical properties. Conserved family motifs can
      be identified by the overlay of similarity plot calculations on a ProfileGrid.
      Figures suitable for publication can be generated from the saved spreadsheet
      output of the colored matrices as well as by the export of conservation
      information for use in the PyMOL molecular visualization program.We demonstrate
      the utility of ProfileGrids on 300 bacterial homologs of the RecA family - a
      universally conserved protein involved in DNA recombination and repair. Careful
      attention was paid to curating the collected RecA sequences since ProfileGrids
      allow the easy identification of rare residues in an alignment. We relate the
      RecA alignment sequence conservation to the following three topics: the recently
      identified DNA binding residues, the unexplored MAW motif, and a unique Bacillus
      subtilis RecA homolog sequence feature. CONCLUSION: ProfileGrids allow large
      protein families to be visualized more effectively than the traditional stacked
      sequence alignment form. This new graphical representation facilitates the
      determination of the sequence conservation at residue positions of interest,
      enables the examination of structural patterns by using residue physical
      properties, and permits the display of rare sequence features within the context
      of an entire alignment. JProfileGrid is free for non-commercial use and is
      available from http://www.profilegrid.org. Furthermore, we present a curated RecA
      protein collection that is more diverse than previous data sets; and, therefore,
      this RecA ProfileGrid is a rich source of information for nanoanatomy analysis.

PMID- 19102759
TI  - In-hospital cerebrovascular complications following orthotopic liver
      transplantation: a retrospective study.
AB  - BACKGROUND: Cerebrovascular complications are severe events following orthotopic
      liver transplantation (OLT). This study aimed to observe the clinical and
      neuroimaging features and possible risk factors of in-hospital cerebrovascular
      complications in the patients who underwent OLT. PATIENTS AND METHODS: We
      retrospectively reviewed 337 consecutive patients who underwent 358 OLTs.
      Cerebrovascular complications were determined by clinical and neuroimaging
      manifestations, and the possible risk factors were analyzed in the patients with
      intracranial hemorrhage. RESULTS: Ten of 337 (3.0%) patients developed in
      hospital cerebrovascular complications (8 cases experienced intracranial
      hemorrhage and 2 cases had cerebral infarction), and 6 of them died. The clinical
      presentations were similar to common stroke, but with rapid deterioration at
      early stage. The hematomas on brain CT scan were massive, irregular, multifocal
      and diffuse, and most of them were located at brain lobes and might enlarge or
      rebleed. Infarcts presented lacunar and multifocal lesions in basal gangliar but
      with possible hemorrhagic transformation. The patients with intracranial
      hemorrhage had older age and a more frequency of systemic infection than non
      intracranial hemorrhage patients. (P = 0.011 and 0.029, respectively).
      CONCLUSION: Posttransplant cerebrovascular complications have severe impact on
      outcome of the patients who received OLT. Older age and systemic infection may be
      the possible risk factors of in-hospital intracranial hemorrhage following OLT.

PMID- 19102760
TI  - Craniofacial features of children with spinal deformities.
AB  - BACKGROUND: The objective of this epidemiological study is to map the dentofacial
      anomalies that can be correlated to the two most frequent spinal diseases
      responsible for postural abnormalities and that can be clinically identified by
      the orthodontic examination. METHODS: Twenty-three children with Scheuermann's
      disease participated in the study (mean age: 14Y8M; SD: 1Y8M), 28 with Scoliosis
      (mean age: 14Y7M; SD: 2Y3M) and a control group of 68 orthopedically healthy
      children (mean age: 14Y8M; SD: 0Y11M). Standardized orthodontic screening
      protocols were used to map the occlusal relations in the sagittal, vertical, and
      transversal dimensions, space relations of the maxillary and mandibular frontal
      segment, and the TMJ status and function. The examinations for the children with
      orthopedic disorders were supplemented by the evaluation of routine orthodontic
      radiograms - lateral cephalograms and panoramic X-rays. RESULTS: The majority of
      the dentofacial features examined revealed more and greater abnormalities among
      patients in the Scheuermann's disease group than in the scoliosis group. In the
      latter group the proportion of the TMJ symptoms and the consecutive functional
      deviations were greater. When comparing the values of the two spinal-disorder
      groups and the control group, statistically significant differences (p < .05)
      occurred for the following measurements: frequency of unilateral Cl.II. molar
      occlusion, overjet and extreme overjet mean value (Scheuermann's disease group),
      as well as the frequency of TMJ pathological symptoms (scoliosis group). The
      evaluation of the panoramic X-rays showed significant differences among the
      mandibular measurements of the two spinal-disorder groups. Within the framework
      of the evaluation of the cephalograms significant differences (p < .05) were
      found only in the case of dental relations. However, several values differed
      significantly from the Ricketts' norms, none of the indices strictly
      characterized any of the groups with spinal disorders. CONCLUSION: The more
      extended treatment of the malocclusions closely correlated to postural disorders
      draws attention to the indicators of a higher frequency and severity occurring in
      the case of the dentofacial deviations in the patients of the MSCH group who had
      previously been less examined.

PMID- 19102761
TI  - Challenges in multidisciplinary cancer care among general surgeons in Canada.
AB  - BACKGROUND: While many factors can influence the way that cancer care is
      delivered, including the way that evidence is packaged and disseminated, little
      research has evaluated how health care professionals who manage cancer patients
      seek and use this information to identify whether and how this could be
      supported. Through interviews we identified that general surgeons experience
      challenges in coordinating care for complex cancer patients whose management is
      not easily addressed by guidelines, and conducted a population-based survey of
      general surgeon information needs and information seeking practices to extend
      these findings. METHODS: General surgeons with privileges at acute care hospitals
      in Ontario, Canada were mailed a questionnaire to solicit information needs
      (task, importance), information seeking (source, frequency of and reasons for
      use), key challenges and suggested solutions. Non-responders received up to three
      reminder packages. Significant differences among sub-groups (age, setting) were
      examined statistically (Kruskal Wallis, Mann Whitney, Chi Square). Standard
      qualitative methods were used to thematically analyze open-ended responses.
      RESULTS: The response rate was 44.2% (170/385) representing all 14 health
      regions. System resource constraints (60.4%), comorbidities (56.4%) and
      physiologic factors (51.8%) were top-ranked issues creating information needs.
      Local surgical colleagues (84.6%), other local colleagues (82.2%) and the
      Internet (81.1%) were top-ranked sources of information, primarily due to
      familiarity and speed of access. No resources were considered to be highly
      applicable to patient care. Challenges were related to limitations in diagnostics
      and staging, operative resources, and systems to support multidisciplinary care,
      together accounting for 76.0% of all reported issues. Findings did not differ
      significantly by surgeon age or setting of care. CONCLUSION: General surgeons
      appear to use a wide range of information resources but they may not address the
      complex needs of many cancer patients. Decision-making is challenged by
      informational and logistical issues related to the coordination of
      multidisciplinary care. This suggests that limitations in system capacity may, in
      part, contribute to variable guideline compliance. Further research is required
      to evaluate the appropriateness of information seeking, and both concurrent and
      consecutive mechanisms by which to achieve multidisciplinary care.

PMID- 19102763
TI  - Using a commercially available DNA extraction kit to obtain high quality human
      genomic DNA suitable for PCR and genotyping from 11-year-old saliva saturated
      cotton spit wads.
AB  - BACKGROUND: We sought to describe the integrity of human genomic DNA extracted
      from saliva saturated cotton spit wads stored at -20 degrees C for approximately
      11 years. 783 spit wad samples were collected from an ADHD sample population
      (Vermont Family Study) during 1996-2000. Human genomic DNA was extracted from the
      spit wads using a commercially available kit; QIAamp DNA Blood Midi Kit (Qiagen,
      Inc., Valencia, CA.) with a few modifications. RESULTS: The resulting DNA yield
      was more than adequate for genetic analysis and ranged from approximately 1 mug
      to a total of 80 mug (mean 17.3 mugs +/- 11.9 mugs). A260/A280 ratios for the
      human genomic DNA extracted from the spit wads was consistently within the
      generally acceptable values of 1.7-2.0, with the lowest purity being 1.70, and a
      mean value of 1.937 +/- 0.226 for the 783 samples. The DNA also was suitable for
      PCR reactions as evidenced by the amplification of the serotonin-transporter
      linked polymorphic region, 5HTTLPR. 5HTTLPR is a functional polymorphism in the
      promoter region of the serotonin transporter gene (HTT, SLC6A4, or SERT),
      consisting of two intensively studied alleles. 770 of the 783 samples (98.3%)
      produced fragments after PCR of the expected size with primers specific for
      5HTTLPR. CONCLUSION: High quality and abundant genomic DNA can be successfully
      retrieved from saliva saturated cotton spit wads using the commercially available
      kit, QIAamp DNA Blood Midi Kit from Qiagen, Inc. Furthermore, the DNA can be
      extracted in less than 3 hours and multiple samples can be processed
      simultaneously thus reducing processing time.

PMID- 19102762
TI  - Expression of centromere protein F (CENP-F) associated with higher FDG uptake on
      PET/CT, detected by cDNA microarray, predicts high-risk patients with primary
      breast cancer.
AB  - BACKGROUND: Higher standardized uptake value (SUV) detected by 18F
      fluorodeoxyglucose positron emission tomography/computed tomography (FDG PET/CT)
      correlates with proliferation of primary breast cancer. The purpose of this study
      is to identify specific molecules upregulated in primary breast cancers with a
      high SUV and to examine their clinical significance. METHODS: We compared mRNA
      expression profiles between 14 tumors with low SUVs and 24 tumors with high SUVs
      by cDNA microarray. We identified centromere protein F (CENP-F) and CDC6 were
      upregulated in tumors with high SUVs. RT-PCR and immunohistochemical analyses
      were performed to validate these data. Clinical implication of CENP-F and CDC6
      was examined for 253 archival breast cancers by the tissue microarray. RESULTS:
      The relative ratios of CENP-F and CDC6 expression levels to beta-actin were
      confirmed to be significantly higher in high SUV tumors than in low SUV tumors (p
      = 0.027 and 0.025, respectively) by RT-PCR. In immunohistochemical analysis of 47
      node-negative tumors, the CENP-F expression was significantly higher in the high
      SUV tumors (74%) than the low SUV tumors (45%) (p = 0.04), but membranous and
      cytoplasmic CDC6 expressions did not significantly differ between both groups (p
      = 0.9 each). By the tissue microarray, CENP-F (HR = 2.94) as well as tumor size
      (HR = 4.49), nodal positivity (HR = 4.1), and Ki67 (HR = 2.05) showed independent
      impact on the patients' prognosis. CONCLUSION: High CENP-F expression, correlated
      with high SUV, was the prognostic indicators of primary breast cancer. Tumoral
      SUV levels may serve as a pretherapeutic indicator of aggressiveness of breast
      cancer.

PMID- 19102764
TI  - Complete genomic sequence analysis of infectious bronchitis virus Ark DPI strain
      and its evolution by recombination.
AB  - An infectious bronchitis virus Arkansas DPI (Ark DPI) virulent strain was
      sequenced, analyzed and compared with many different IBV strains and
      coronaviruses. The genome of Ark DPI consists of 27,620 nucleotides, excluding
      poly (A) tail, and comprises ten open reading frames. Comparative sequence
      analysis of Ark DPI with other IBV strains shows striking similarity to the Conn,
      Gray, JMK, and Ark 99, which were circulating during that time period.
      Furthermore, comparison of the Ark genome with other coronaviruses demonstrates a
      close relationship to turkey coronavirus. Among non-structural genes, the
      5'untranslated region (UTR), 3C-like proteinase (3CLpro) and the polymerase
      (RdRp) sequences are 100% identical to the Gray strain. Among structural genes,
      S1 has 97% identity with Ark 99; S2 has 100% identity with JMK and 96% to Conn;
      3b 99%, and 3C to N is 100% identical to Conn strain. Possible recombination
      sites were found at the intergenic region of spike gene, 3'end of S1 and 3a gene.
      Independent recombination events may have occurred in the entire genome of Ark
      DPI, involving four different IBV strains, suggesting that genomic RNA
      recombination may occur in any part of the genome at number of sites. Hence, we
      speculate that the Ark DPI strain originated from the Conn strain, but diverged
      and evolved independently by point mutations and recombination between field
      strains.

PMID- 19102765
TI  - The symptom experience of people living with HIV and AIDS in the Eastern Cape,
      South Africa.
AB  - BACKGROUND: Symptom management for persons living with HIV (PLHIV) or AIDS is an
      important part of care management. Limited information about symptom prevalence
      exists about HIV infected persons in South Africa, in particular in the context
      of antiretroviral treatment (ART). The aim of this study was to assess HIV
      symptoms and demographic, social and disease variables of people living with HIV
      in South Africa. METHODS: In 2007 607 PLHIV, sampled by all districts in the
      Eastern Cape Province and recruited through convenience sampling, were
      interviewed by PLHIV at health facilities, key informants in the community and
      support groups. RESULTS: Two-thirds of the PLHIV (66%) classified themselves with
      being given an AIDS (advanced stage of HIV) diagnosis, 48% were currently on ART,
      35% were currently on a disability grant for HIV/AIDS and for 13% the disability
      grant had been stopped. Participants reported that on the day of the interview,
      they were experiencing an average of 26.1 symptoms out of a possible 64. In a
      regression model with demographic and social variables, higher HIV symptom levels
      were associated with lower educational levels, higher age, urban residence and
      not on a disability grant, lack of enough food and having a health insurance, and
      in a regression model with demographic, social and disease variables only being
      on ART, lack of enough food and having a health insurance were associated with
      HIV symptoms. CONCLUSION: Symptom assessment provides information that may be
      valuable in evaluating AIDS treatment regimens and defining strategies to improve
      quality of life. Because of the high levels of symptoms reported, the results
      imply an urgent need for effective health care, home- and community-based as well
      as self-care symptom management to help patients and their families manage and
      control AIDS symptoms.

PMID- 19102766
TI  - Imbalances in faecal and duodenal Bifidobacterium species composition in active
      and non-active coeliac disease.
AB  - BACKGROUND: Gut bifidobacteria are believed to influence immune-related diseases.
      The objective of this study was to assess the possible relationships between the
      gut bifidobacteria composition and coeliac disease (CD) in children. A total of
      48 faecal samples (30 and 18 samples from active and no active CD patients,
      respectively) and 33 duodenal biopsy specimens of CD patients (25 and 8 samples
      from active and non-active CD patients, respectively) were analysed. Samples (30
      faecal samples and 8 biopsies) from a control age-matched group of children were
      also included for comparative purposes. Gut Bifidobacterium genus and species
      were analyzed by real-time PCR. RESULTS: Active and non-active CD patients showed
      lower numbers of total Bifidobacterium and B. longum species in faeces and
      duodenal biopsies than controls, and these differences were particularly
      remarkable between active CD patients and controls. B. catenulatum prevalence was
      higher in biopsies of controls than in those of active and non-active CD
      patients, whereas B. dentium prevalence was higher in faeces of non-active CD
      patients than in controls. Correlations between levels of Bifidobacterium and B.
      longum species in faecal and biopsy samples were detected in both CD patients and
      controls. CONCLUSION: Reductions in total Bifidobacterium and B. longum
      populations were associated with both active and non-active CD when compared to
      controls. These bacterial groups could constitute novel targets for adjuvant
      dietary therapies although the confirmation of this hypothesis would require
      further investigations.

PMID- 19102767
TI  - Hepatitis E virus is highly prevalent among pregnant women in Gabon, central
      Africa, with different patterns between rural and urban areas.
AB  - Hepatitis E virus (HEV) is highly endemic in several African countries with high
      mortality rate among pregnant women. Nothing is known about the circulation of
      this virus in central Africa. We evaluated therefore the prevalence of anti-HEV
      IgG in samples collected from pregnant women living in the five main cities of
      Gabon, central Africa. We found that 14.1% (119/840) of pregnant women had anti
      HEV IgG. The prevalence differed between regions and between age groups. In 391
      newly collected samples from the region where the highest prevalence was found, a
      significant difference (p < 0.05) in seroprevalence was found between rural
      (6.4%) and urban (13.5%) areas. These data provide evidence of a high prevalence
      of HEV in Gabon, providing indirect evidence of past contact with this virus.

PMID- 19102768
TI  - Molecular epidemiology and evolutionary genetics of Mycobacterium tuberculosis in
      Taipei.
AB  - BACKGROUND: The control of tuberculosis in densely populated cities is
      complicated by close human-to-human contacts and potential transmission of
      pathogens from multiple sources. We conducted a molecular epidemiologic analysis
      of 356 Mycobacterium tuberculosis (MTB) isolates from patients presenting
      pulmonary tuberculosis in metropolitan Taipei. Classical antibiogram studies and
      genetic characterization, using mycobacterial interspersed repetitive-unit
      variable-number tandem-repeat (MIRU-VNTR) typing and spoligotyping, were applied
      after culture. METHODS: A total of 356 isolates were genotyped by standard
      spoligotyping and the strains were compared with in the international
      spoligotyping database (SpolDB4). All isolates were also categorized using the 15
      loci MIRU-VNTR typing method and combin with NTF locus and RD deletion analyses.
      RESULTS: Of 356 isolates spoligotyped, 290 (81.4%) displayed known spoligotypes
      and 66 were not identified in the database. Major spoligotypes found were Beijing
      lineages (52.5%), followed by Haarlem lineages (13.5%) and EAI plus EAI-like
      lineages (11%). When MIRU-VNTR was employed, 140 patterns were identified,
      including 36 clusters by 252 isolates and 104 unique patterns, and the largest
      cluster comprised 95 isolates from the Beijing family. The combination of
      spoligotyping and MIRU-VNTR revealed that 236 (67%) of the 356 isolates were
      clustered in 43 genotypes. Strains of the Beijing family was more likely to be of
      modern strain and a higher percentage of multiple drug resistance than other
      families combined (P = 0.08). Patients infected with Beijing strains were younger
      than those with other strains (mean 58.7 vs. 64.2, p = 0.02). Moreover, 85.3% of
      infected persons younger than 25 years had Beijing modern strain, suggesting a
      possible recent spread in the young population by this family of TB strain in
      Taipei. CONCLUSION: Our data on MTB genotype in Taipei suggest that MTB infection
      has not been optimally controlled. Control efforts should be reinforced in view
      of the high prevalence of the Beijing strain in young population and association
      with drug resistance.

PMID- 19102769
TI  - Relationship between total lymphocyte count (TLC) and CD4 count among peoples
      living with HIV, Southern Ethiopia: a retrospective evaluation.
AB  - BACKGROUND: CD4 count is a standard measure of immunodeficiency in adults
      infected with HIV to initiate and monitor highly active antiretroviral therapy;
      however, it may not be feasible in resource poor countries. There is a need to
      have another marker of immunodeficiency that is less resource demanding.
      OBJECTIVE: The objective of this study was to assess the relationship between
      total lymphocyte count and CD4 count in one of the resource poor countries,
      Ethiopia. METHODS: This was a retrospective evaluation. A total of 2019 cases
      with total lymphocyte and CD4 counts from three hospitals (Yirgalem, Hossana and
      Arba-Minch) were included in the study. Pearson correlation, linear regression
      and Receiver Operating Characteristic (ROC) were used. RESULT: For adults, the
      sensitivity, specificity, positive and negative predictive values of TLC < 1200
      cells/mm3 to predict CD4 count < 200 cells/mm3 were 41%, 83.5%, 87.9% and 32.5%,
      respectively. For subjects aged less than 18 years, these values were 20.2%, 87%,
      82% and 27.1%, respectively. A TLC </= 1780 cells/mm3 was found to have maximal
      sensitivity (61%) and specificity (62%) for predicting a CD4 cell count of < 200
      cells/mm3. Meanwhile, a TLC </= 1885 cells/mm3 would identify only 59% of
      patients with CD4 count of < 350 cells/mm3(sensitivity, 59%; and specificity,
      61%). The combined sensitivity and specificity for patients above 40 years of age
      was greater. CONCLUSION: Our data revealed low sensitivity and specificity of TLC
      as a surrogate measure for CD4 count.

PMID- 19102770
TI  - Three-year follow-up of physical activity in Norwegian youth from two ethnic
      groups: associations with socio-demographic factors.
AB  - BACKGROUND: More research on factors associated with physical activity and the
      decline in participation during adolescence is needed. In this paper, we
      investigate the levels, change, and stability of physical activity during the
      late teens among ethnic Norwegians and ethnic minorities, and we examine the
      associations between physical activity and socio-demographic factors. METHODS:
      The baseline (T1) of this longitudinal study included 10th graders who
      participated in the youth part of the Oslo Health Study, which was carried out in
      schools in 2000-2001. The follow-up (T2) in 2003-2004 was conducted partly at
      school and partly by mail. A total of 2489 (1112 boys and 1377 girls)
      participated both at baseline and at follow-up. Physical activity level was
      measured by a question on weekly hours of physical activity outside of school.
      Socio-demographic variables were collected by questionnaire and from data
      obtained from Statistics Norway. Analysis of variance was used to study the level
      of and changes (T1 to T2) in physical activity, and the associations between
      physical activity and socio-demographic factors. Stability in physical activity
      was defined as the percentage of students reporting the same physical activity
      both times. RESULTS: Boys were more active than girls at age 15 and 18 years,
      independent of ethnic background. Among girls, ethnic Norwegians were more active
      than ethnic minorities. Hours per week spent on physical activity declined in all
      groups during the follow-up period. Few associations were found between physical
      activity and socio-demographic factors in both cross-sectional and longitudinal
      data. Among the ethnic minority girls, 65% reported being physically active 0-2
      hours per week at baseline, and 82% of these girls reported the same level at
      follow up. CONCLUSION: The association between physical activity and ethnicity at
      age 15 years remained the same during the follow-up. Few associations were found
      between physical activity and socio-demographic variables. A large proportion of
      ethnic minority girls reported a persistently low physical activity level, and
      this low participation rate may need special attention.

PMID- 19102771
TI  - Successful laparoscopic management of concomitant ectopic pregnancy and acute
      appendicitis in a patient of failed tubal ligation - case report with a review of
      the literature.
AB  - BACKGROUND: The incidence of failed abdominal bilateral tubal ligation (BTL) is
      quite low. Most often the pregnancy following BTL is ectopic in location. The
      association of concurrent acute appendicitis with ectopic pregnancy is also very
      rare. From 1960 till 2008 only 23 such cases of ectopic pregnancy with
      appendicitis managed by open surgery have been reported in the medical
      literature. CASE PRESENTATION: We present a case in which the patient had
      concurrent ectopic pregnancy of the right fallopian tube with acute appendicitis
      after failed BTL and which was managed successfully by laparoscopic approach.
      CONCLUSION: Although the combination of ectopic pregnancy and acute appendicitis
      is quite rare, it is wise to rule out concurrent acute appendicitis in patients
      of ectopic pregnancy especially if it is on the right side due to an inter
      etiological relationship. Laparoscopic management of both these pathologies can
      be accomplished quite successfully in properly selected cases.

PMID- 19102772
TI  - Identification of a novel picornavirus related to cosaviruses in a child with
      acute diarrhea.
AB  - Diarrhea, the third leading infectious cause of death worldwide, causes
      approximately 2 million deaths a year. Approximately 40% of these cases are of
      unknown etiology. We previously developed a metagenomic strategy for
      identification of novel viruses from diarrhea samples. By applying mass
      sequencing to a stool sample collected in Melbourne, Australia from a child with
      acute diarrhea, one 395 bp sequence read was identified that possessed only
      limited identity to known picornaviruses. This initial fragment shared only 55%
      amino acid identity to its top BLAST hit, the VP3 protein of Theiler's-like
      virus, suggesting that a novel picornavirus might be present in this sample. By
      using a combination of mass sequencing, RT-PCR, 5' RACE and 3' RACE, 6562 bp of
      the viral genome was sequenced, which includes the entire putative polyprotein.
      The overall genomic organization of this virus was similar to known
      picornaviruses. Phylogenetic analysis of the polyprotein demonstrated that the
      virus was divergent from previously described picornaviruses and appears to
      belong to the newly proposed picornavirus genus, Cosavirus. Based on the analysis
      discussed here, we propose that this virus represents a new species in the
      Cosavirus genus, and it has tentatively been named Human Cosavirus E1 (HCoSV-E1).

PMID- 19102773
TI  - RPPAML/RIMS: a metadata format and an information management system for reverse
      phase protein arrays.
AB  - BACKGROUND: Reverse Phase Protein Arrays (RPPA) are convenient assay platforms to
      investigate the presence of biomarkers in tissue lysates. As with other high
      throughput technologies, substantial amounts of analytical data are generated.
      Over 1,000 samples may be printed on a single nitrocellulose slide. Up to 100
      different proteins may be assessed using immunoperoxidase or immunoflorescence
      techniques in order to determine relative amounts of protein expression in the
      samples of interest. RESULTS: In this report an RPPA Information Management
      System (RIMS) is described and made available with open source software. In order
      to implement the proposed system, we propose a metadata format known as reverse
      phase protein array markup language (RPPAML). RPPAML would enable researchers to
      describe, document and disseminate RPPA data. The complexity of the data
      structure needed to describe the results and the graphic tools necessary to
      visualize them require a software deployment distributed between a client and a
      server application. This was achieved without sacrificing interoperability
      between individual deployments through the use of an open source semantic
      database, S3DB. This data service backbone is available to multiple client side
      applications that can also access other server side deployments. The RIMS
      platform was designed to interoperate with other data analysis and data
      visualization tools such as Cytoscape. CONCLUSION: The proposed RPPAML data
      format hopes to standardize RPPA data. Standardization of data would result in
      diverse client applications being able to operate on the same set of data.
      Additionally, having data in a standard format would enable data dissemination
      and data analysis.

PMID- 19102774
TI  - DNA methylation and mRNA expression of SYN III, a candidate gene for
      schizophrenia.
AB  - BACKGROUND: The synapsin III (SYN III) gene on chromosome 22q is a candidate gene
      for schizophrenia susceptibility due to its chromosome location, neurological
      function, expression patterns and functional polymorphisms. METHODS: This
      research has established the mRNA expression of SYN III in 22 adult human brain
      regions as well as the methylation specificity in the closest CpG island of this
      gene. The methylation specificity studied in 31 brain regions (from a single
      individual) was also assessed in 51 human blood samples (representing 20 people
      affected with schizophrenia and 31 normal controls) including a pair of
      monozygotic twin discordant for schizophrenia and 2 non-human primates. RESULTS:
      The results show that the cytosine methylation in this genomic region is 1)
      restricted to cytosines in CpG dinucleotides 2) similar in brain regions and
      blood and 3) appears conserved in primate evolution. Two cytosines (cytosine 8
      and 20) localized as the CpG dinucleotide are partially methylated in all brain
      regions studied. The methylation of these sites in schizophrenia and control
      blood samples was variable. While cytosine 8 was partially methylated in all
      samples, the distribution of partial to complete methylation at the cytosine 20
      was 22:9 in controls as compared to 18:2 in schizophrenia (p = 0.82). Also, there
      is no difference in methylation between the affected and unaffected member of a
      monozygotic twin pair. CONCLUSION: The variation in SYN III methylation studied
      is 1) not related to schizophrenia in the population sample or a monozygotic twin
      pair discordant for schizophrenia and 2) not related to the mRNA level of SYN
      IIIa in different human brain regions.

PMID- 19102776
TI  - Post-traumatic myositis ossificans of the sternocleidomastoid following fracture
      of the clavicle: a case report.
AB  - BACKGROUND: Fractures of the clavicle are common injuries. The complications have
      been well documented in the literature. CASE PRESENTATION: Despite it close
      proximity to the sternocleidomastoid muscle and myositis ossificans recognised as
      a known complication of any fracture, the two have never previously been
      described in association secondary to a fracture of the clavicle. We present a
      case where myositis ossificans affecting the sternocleiodomastoid was detected in
      the post-injury phase of a clavicle fracture. CONCLUSION: This case highlights
      that traumatic myositis ossificans circumscipta can arise in the
      sternocleidomastoid muscle following a fracture of the medial third of the
      clavicle.

PMID- 19102775
TI  - Selecting a BRCA risk assessment model for use in a familial cancer clinic.
AB  - BACKGROUND: Risk models are used to calculate the likelihood of carrying a BRCA1
      or BRCA2 mutation. We evaluated the performances of currently-used risk models
      among patients from a large familial program using the criteria of high
      sensitivity, simple data collection and entry and BRCA score reporting. METHODS:
      Risk calculations were performed by applying the BRCAPRO, Manchester, Penn II,
      Myriad II, FHAT, IBIS and BOADICEA models to 200 non-BRCA carriers and 100 BRCA
      carriers, consecutively tested between August 1995 and March 2006. Areas under
      the receiver operating characteristic curves (AUCs) were determined and
      sensitivity and specificity were calculated at the conventional testing
      thresholds. In addition, subset analyses were performed for low and high risk
      probands. RESULTS: The BRCAPRO, Penn II, Myriad II, FHAT and BOADICEA models all
      have similar AUCs of approximately 0.75 for BRCA status. The Manchester and IBIS
      models have lower AUCs (0. and 0.47 respectively). At the conventional testing
      thresholds, the sensitivities and specificities for a BRCA mutation were,
      respectively, as follows: BRCAPRO (0.75, 0.62), Manchester (0.58,0.71), Penn II
      (0.93,0.31), Myriad II (0.71,0.63), FHAT (0.70,0.63), IBIS (0.20,0.74), BOADICEA
      (0.70, 0.65). CONCLUSION: The Penn II model most closely met the criteria we
      established and this supports the use of this model for identifying individuals
      appropriate for genetic testing at our facility. These data are applicable to
      other familial clinics provided that variations in sample populations are taken
      into consideration.

PMID- 19102777
TI  - (S)Partners for Heart Health: a school-based program for enhancing physical
      activity and nutrition to promote cardiovascular health in 5th grade students.
AB  - BACKGROUND: The American Heart Association Position Statement on Cardiovascular
      Health Promotion in Public Schools encourages school-based interventions for the
      primary prevention of cardiovascular disease (CVD) through risk factor prevention
      or reduction in children with an emphasis on creating an environment that
      promotes healthy food choices and physical activity (PA). In an effort to address
      issues related to CVD risk factors including obesity in Michigan children, a
      multi-disciplinary team of Michigan State University (MSU) faculty, clinicians,
      and health profession students was formed to "(S)partner" with elementary school
      physical education (PE) teachers and MSU Extension staff to develop and implement
      a cost-effective, sustainable program aimed at CVD risk factor prevention and
      management for 5th grade students. This (S)partnership is intended to augment and
      improve the existing 5th grade PE, health and nutrition curriculum by achieving
      the following aims: 1) improve the students' knowledge, attitudes and confidence
      about nutrition, PA and heart health; 2) increase the number of students
      achieving national recommendations for PA and nutrition; and 3) increase the
      number of students with a desirable CVD risk factor status based on national
      pediatric guidelines. Secondary aims include promoting school staff and parental
      support for heart health to help children achieve their goals and to provide
      experiential learning and service for MSU health profession students for academic
      credit. METHODS/DESIGN: This pilot effectiveness study was approved by the MSU
      IRB. At the beginning and the end of the school year students undergo a CVD risk
      factor assessment conducted by MSU medical students and graduate students. Key
      intervention components include eight lesson plans (conducted bi-monthly)
      designed to promote heart healthy nutrition and PA behaviors conducted by PE
      teachers with assistance from MSU undergraduate dietetic and kinesiology students
      (Spartners). The final 10 minutes of each lesson, MSU Spartners conduct small
      breakout/discussion groups with the 5th grade students. Additionally, each
      Spartner case manages/mentors two to three 5th grade students using a web-based
      goal setting and tracking protocol throughout the school year. DISCUSSION: This
      paper describes the rationale, development, and methods of the Spartners for
      Heart Health program. This is a multi-level intervention designed to promote
      heart healthy behaviors and prevent or manage CVD risk factors in children. We
      believe this will be a viable sustainable intervention that can be disseminated
      and adopted by other institutions with minimal cost by engaging college students
      as an integral part of the measurement and intervention teams.

PMID- 19102778
TI  - Is there an association between fibromyalgia and below-normal levels of urinary
      cortisol?
AB  - BACKGROUND: Adynamia in fibromyalgia (FM) may be an expression of a functional
      deficit of the hypothalamic-pituitary-adrenal axis and be associated with below
      normal levels of urinary cortisol. Our aim was to demonstrate that urinary
      cortisol was lower in patients with FM than in healthy subjects. FINDINGS: We
      measured urinary cortisol levels for a sample of 47 women aged 29 to 64 years
      (mean age 53 years), diagnosed with FM 2-3 years previously, and compared the
      results with those for a control sample of 58 healthy women of a similar age.
      Samples of 24-hour urine were appropriately collected and levels of urinary
      cortisol were measured using the fluorescence polarization immunoassay method.
      The mean cortisol value for the women with FM was 65.40 +/- 27.10 mug/L,
      significantly lower than the mean cortisol level for the control group, at 90.83
      +/- 38.17 mug/L (p < 0.001). CONCLUSION: Our study confirms that women with FM
      have significantly lower urinary cortisol levels than healthy women.

PMID- 19102779
TI  - Elicitor-induced transcription factors for metabolic reprogramming of secondary
      metabolism in Medicago truncatula.
AB  - BACKGROUND: Exposure of Medicago truncatula cell suspension cultures to pathogen
      or wound signals leads to accumulation of various classes of flavonoid and/or
      triterpene defense molecules, orchestrated via a complex signalling network in
      which transcription factors (TFs) are essential components. RESULTS: In this
      study, we analyzed TFs responding to yeast elicitor (YE) or methyl jasmonate
      (MJ). From 502 differentially expressed TFs, WRKY and AP2/EREBP gene families
      were over-represented among YE-induced genes whereas Basic Helix-Loop-Helix
      (bHLH) family members were more over-represented among the MJ-induced genes.
      Jasmonate ZIM-domain (JAZ) transcriptional regulators were highly induced by MJ
      treatment. To investigate potential involvement of WRKY TFs in signalling, we
      expressed four Medicago WRKY genes in tobacco. Levels of soluble and wall bound
      phenolic compounds and lignin were increased in all cases. WRKY W109669 also
      induced tobacco endo-1,3-beta-glucanase (NtPR2) and enhanced the systemic defense
      response to tobacco mosaic virus in transgenic tobacco plants. CONCLUSION: These
      results confirm that Medicago WRKY TFs have broad roles in orchestrating
      metabolic responses to biotic stress, and that they also represent potentially
      valuable reagents for engineering metabolic changes that impact pathogen
      resistance.

PMID- 19102780
TI  - HuMiTar: a sequence-based method for prediction of human microRNA targets.
AB  - BACKGROUND: MicroRNAs (miRs) are small noncoding RNAs that bind to
      complementary/partially complementary sites in the 3' untranslated regions of
      target genes to regulate protein production of the target transcript and to
      induce mRNA degradation or mRNA cleavage. The ability to perform accurate, high
      throughput identification of physiologically active miR targets would enable
      functional characterization of individual miRs. Current target prediction methods
      include traditional approaches that are based on specific base-pairing rules in
      the miR's seed region and implementation of cross-species conservation of the
      target site, and machine learning (ML) methods that explore patterns that
      contrast true and false miR-mRNA duplexes. However, in the case of the
      traditional methods research shows that some seed region matches that are
      conserved are false positives and that some of the experimentally validated
      target sites are not conserved. RESULTS: We present HuMiTar, a computational
      method for identifying common targets of miRs, which is based on a scoring
      function that considers base-pairing for both seed and non-seed positions for
      human miR-mRNA duplexes. Our design shows that certain non-seed miR nucleotides,
      such as 14, 18, 13, 11, and 17, are characterized by a strong bias towards
      formation of Watson-Crick pairing. We contrasted HuMiTar with several
      representative competing methods on two sets of human miR targets and a set of
      ten glioblastoma oncogenes. Comparison with the two best performing traditional
      methods, PicTar and TargetScanS, and a representative ML method that considers
      the non-seed positions, NBmiRTar, shows that HuMiTar predictions include majority
      of the predictions of the other three methods. At the same time, the proposed
      method is also capable of finding more true positive targets as a trade-off for
      an increased number of predictions. Genome-wide predictions show that the
      proposed method is characterized by 1.99 signal-to-noise ratio and linear, with
      respect to the length of the mRNA sequence, computational complexity. The ROC
      analysis shows that HuMiTar obtains results comparable with PicTar, which are
      characterized by high true positive rates that are coupled with moderate values
      of false positive rates. CONCLUSION: The proposed HuMiTar method constitutes a
      step towards providing an efficient model for studying translational gene
      regulation by miRs.

PMID- 19102781
TI  - Human cellular microRNA hsa-miR-29a interferes with viral nef protein expression
      and HIV-1 replication.
AB  - BACKGROUND: Cellular miRNAs play an important role in the regulation of gene
      expression in eukaryotes. Recently, miRNAs have also been shown to be able to
      target and inhibit viral gene expression. Computational predictions revealed
      earlier that the HIV-1 genome includes regions that may be potentially targeted
      by human miRNAs. Here we report the functionality of predicted miR-29a target
      site in the HIV-1 nef gene. RESULTS: We find that the human miRNAs hsa-miR-29a
      and 29b are expressed in human peripheral blood mononuclear cells. Expression of
      a luciferase reporter bearing the nef miR-29a target site was decreased compared
      to the luciferase construct without the target site. Locked nucleic acid modified
      anti-miRNAs targeted against hsa-miR-29a and 29b specifically reversed the
      inhibitory effect mediated by cellular miRNAs on the target site. Ectopic
      expression of the miRNA results in repression of the target Nef protein and
      reduction of virus levels. CONCLUSION: Our results show that the cellular miRNA
      hsa-miR29a downregulates the expression of Nef protein and interferes with HIV-1
      replication.

PMID- 19102783
TI  - Cigarettes-induced acute eosinophilic pneumonia: a case report.
AB  - BACKGROUND: Idiopathic acute eosinophilic pneumonia is a rare disease. It
      presents with acute febrile illness, respiratory insufficiency, pulmonary
      infiltration and high eosinophil levels in Bronchoalveolar lavage fluid.
      Pathogenesis is not well understood, but may relate to the exposure to exogenous
      substances. CASE PRESENTATION: We present a case of 20-year-old man, who
      developed idiopathic acute eosinophilic pneumonia after smoking cigarettes and
      required intubation with mechanical ventilation. His symptoms resolved quickly
      after corticosteroids therapy. CONCLUSION: Acute eosinophilic pneumonia should be
      considered in the differential diagnosis of a patient with acute febrile
      respiratory illness, diffuse bilateral pulmonary infiltrates and recent
      modification in smoking habit.

PMID- 19102782
TI  - Microarray-based approach identifies microRNAs and their target functional
      patterns in polycystic kidney disease.
AB  - BACKGROUND: MicroRNAs (miRNAs) play key roles in mammalian gene expression and
      several cellular processes, including differentiation, development, apoptosis and
      cancer pathomechanisms. Recently the biological importance of primary cilia has
      been recognized in a number of human genetic diseases. Numerous disorders are
      related to cilia dysfunction, including polycystic kidney disease (PKD). Although
      involvement of certain genes and transcriptional networks in PKD development has
      been shown, not much is known how they are regulated molecularly. RESULTS: Given
      the emerging role of miRNAs in gene expression, we explored the possibilities of
      miRNA-based regulations in PKD. Here, we analyzed the simultaneous expression
      changes of miRNAs and mRNAs by microarrays. 935 genes, classified into 24
      functional categories, were differentially regulated between PKD and control
      animals. In parallel, 30 miRNAs were differentially regulated in PKD rats: our
      results suggest that several miRNAs might be involved in regulating genetic
      switches in PKD. Furthermore, we describe some newly detected miRNAs, miR-31 and
      miR-217, in the kidney which have not been reported previously. We determine
      functionally related gene sets, or pathways to reveal the functional correlation
      between differentially expressed mRNAs and miRNAs. CONCLUSION: We find that the
      functional patterns of predicted miRNA targets and differentially expressed mRNAs
      are similar. Our results suggest an important role of miRNAs in specific pathways
      underlying PKD.

PMID- 19102784
TI  - A test of financial incentives to improve warfarin adherence.
AB  - BACKGROUND: Sub-optimal adherence to warfarin places millions of patients at risk
      for stroke and bleeding complications each year. Novel methods are needed to
      improve adherence for warfarin. We conducted two pilot studies to determine
      whether a lottery-based daily financial incentive is feasible and improves
      warfarin adherence and anticoagulation control. METHODS: Volunteers from the
      University of Pennsylvania Anticoagulation Management Center who had taken
      warfarin for at least 3 months participated in either a pilot study with a
      lottery with a daily expected value of $5 (N = 10) or a daily expected value of
      $3 (N = 10). All subjects received use of an Informedix Med-eMonitor System with
      a daily reminder feature. If subjects opened up their pill compartments
      appropriately, they were entered into a daily lottery with a 1 in 5 chance of
      winning $10 and a 1 in 100 chance of winning $100 (pilot 1) or a 1 in 10 chance
      of winning $10 and a 1 in 100 chance of winning $100 (pilot 2). The primary study
      outcome was proportion of incorrect warfarin doses. The secondary outcome was
      proportion of INR measurements not within therapeutic range. Within-subject pre
      post comparisons were done of INR measurements with comparisons with either
      historic means or within-subject comparisons of incorrect warfarin doses.
      RESULTS: In the first pilot, the percent of out-of-range INRs decreased from
      35.0% to 12.2% during the intervention, before increasing to 42% post
      intervention. The mean proportion of incorrect pills taken during the
      intervention was 2.3% incorrect pills, compared with a historic mean of 22%
      incorrect pill taking in this clinic population. Among the five subjects who also
      had MEMS cap adherence data from warfarin use in our prior study, mean incorrect
      pill taking decreased from 26% pre-pilot to 2.8% in the pilot. In the second
      pilot, the time out of INR range decreased from 65.0% to 40.4%, with the
      proportion of mean incorrect pill taking dropping to 1.6%. CONCLUSION: A daily
      lottery-based financial incentive demonstrated the potential for significant
      improvements in missed doses of warfarin and time out of INR range. Further
      testing should be done of this approach to determine its effectiveness and
      potential application to both warfarin and other chronic medications.

PMID- 19102785
TI  - Advantage of vacuum assisted closure on healing of wound associated with
      omentoplasty after abdominoperineal excision: a case report.
AB  - BACKGROUND: Primary closure of the perineum with drainage after abdominoperineal
      excision of the rectum for carcinoma, is widely accepted. However hematoma,
      perineal abscess and re-operation are significantly more frequent after primary
      closure than after packing of the perineal cavity. Those complications are
      frequently related to the patients' clinical antecedent (i.e radiotherapy,
      diabetes, smoking). CASE PRESENTATION: In the present report, vacuum assisted
      drainage was used after abdominoperineal excision for carcinoma in the very first
      step due to intraoperative gross septic contamination during tumor resection. The
      first case: A 57-years old man with a 30-years history of peri-anal Crohn's
      disease, the adenocarcinoma of the lowest part of the rectum and Crohn colitis
      with multiple area of severe dysplasia required panproctocolectomy with a
      perineal resection. The VAC system was used during 12 days (changed every 3
      days). We observed complete healing 18 days after surgery. The second case: A 51
      year-old man, with AIDS. An abdominoperineal resection was performed for
      recurrence epidermoid anal cancer. The patient was discharged at day 25 and
      complete healing was achieved 30 days later after surgery. CONCLUSION: The
      satisfactory results showed in the present report appear to be favored by
      association of omentoplasty and VAC system. Those findings led us to favor VAC
      system in the case of pelvic exenteration associated with high risk of infection.

PMID- 19102786
TI  - Editorial: symposium on antimicrobial resistance in bacteria from animals.

PMID- 19102787
TI  - Antimicrobial resistance: its emergence and transmission.
AB  - New concepts have emerged in the past few years that help us to better understand
      the emergence and spread of antimicrobial resistance (AMR). These include, among
      others, the discovery of the mutator state and the concept of mutant selection
      window for resistances emerging primarily through mutations in existing genes.
      Our understanding of horizontal gene transfer has also evolved significantly in
      the past few years, and important new mechanisms of AMR transfer have been
      discovered, including, among others, integrative conjugative elements and ISCR
      (insertion sequences with common regions) elements. Simultaneously, large-scale
      studies have helped us to start comprehending the immense and yet untapped
      reservoir of both AMR genes and mobile genetic elements present in the
      environment. Finally, new PCR- and DNA sequencing-based techniques are being
      developed that will allow us to better understand the epidemiology of classical
      vectors of AMR genes, such as plasmids, and to monitor them in a more global and
      systematic way.

PMID- 19102788
TI  - Antimicrobial resistance in selected bacteria from poultry.
AB  - This paper reviews the present state of antimicrobial resistance (AMR) in the
      zoonotic bacteria Salmonella, Campylobacter jejuni and Campylobacter coli, and in
      Escherichia coli from chickens and turkeys. For Salmonella, the frequencies and
      patterns of AMR vary depending on time, region, serovar, the particular farm,
      layers versus broilers, and the antimicrobial agent. There is usually a higher
      frequency of AMR in Salmonella from turkeys compared with Salmonella from
      chickens. Clonal and horizontal transmission of AMR occur and there is concern
      about the spread of transmissible plasmids that encode extended spectrum
      cephalosporinases. Resistance to fluoroquinolones is generally low. For
      Campylobacter, resistance to tetracycline is usually at moderate to high
      frequency, resistance to quinolones/fluoroquinolones varies from low to high, and
      resistance to macrolides is usually low. There are high levels of fluoroquinolone
      resistance in some countries. Avian pathogenic E. coli are often highly
      resistant, especially to tetracycline, streptomycin, and sulfonamides. Plasmid
      mediated resistance is common. High levels of resistance to ciprofloxacin have
      been reported from China. Commensal E. coli from poultry have similar patterns of
      resistance but at lower frequencies. Integron associated resistance occurs
      commonly in Salmonella and E. coli but has not been detected in Campylobacter.

PMID- 19102789
TI  - Antimicrobial resistance in zoonotic bacteria: lessons learned from host-specific
      pathogens.
AB  - The relative contribution of veterinary and human clinical treatments to the
      selection of antimicrobial resistance in zoonotic pathogens remains
      controversial. In this review, we consider bacterial pathogens that differ in
      host specificity and address their resistance profiles: pathogens that only occur
      in the human host, pathogens that are specific to particular food-producing
      animals and pathogens that occur in both host types. Compared with those
      pathogens restricted to a single animal host, pathogens found in both human and
      animal hosts appear to have higher incidences of resistance. However, the most
      urgent and severe resistance problems occur with pathogens exclusively infecting
      humans. Differences exist in the available genetic repertoire of a bacterial
      species and these are reflected in the observed resistance patterns; it is
      important to note that different bacterial species do not automatically result in
      similarly resistant populations when they undergo comparable selection in
      different host species. Thus, within a bacterial species, prevalence of
      resistance can differ between populations isolated from different hosts. For some
      species, fluctuations in dominant subpopulations, for instance particular
      serotypes, can be the most important factor determining resistance. The
      frequently expressed opinion that veterinary use of antimicrobials is at the
      heart of many resistance problems may be an oversimplification of the complex
      forces at play.

PMID- 19102790
TI  - Veterinary vaccines: alternatives to antibiotics?
AB  - The prevention of infectious diseases of animals by vaccination has been
      routinely practiced for decades and has proved to be one of the most cost
      effective methods of disease control. However, since the pioneering work of
      Pasteur in the 1880s, the composition of veterinary vaccines has changed very
      little from a conceptual perspective and this has, in turn, limited their
      application in areas such as the control of chronic infectious diseases. New
      technologies in the areas of vaccine formulation and delivery as well as our
      increased knowledge of disease pathogenesis and the host responses associated
      with protection from disease offer promising alternatives for vaccine formulation
      as well as targets for the prevention of bacterial disease. These new vaccines
      have the potential to lessen our reliance on antibiotics for disease control, but
      will only reach their full potential when used in combination with other
      intervention strategies.

PMID- 19102791
TI  - Bacteriophages for prophylaxis and therapy in cattle, poultry and pigs.
AB  - The successful use of virulent (lytic) bacteriophages (phages) in preventing and
      treating neonatal enterotoxigenic Escherichia coli infections in calves, lambs
      and pigs has prompted investigation of other applications of phage therapy in
      food animals. While results have been very variable, some indicate that phage
      therapy is potentially useful in virulent Salmonella and E. coli infections in
      chickens, calves and pigs, and in control of the food-borne pathogens Salmonella
      and Campylobacter jejuni in chickens and E. coli O157:H7 in cattle. However, more
      rigorous and comprehensive research is required to determine the true potential
      of phage therapy. Particular challenges include the selection and
      characterization of phages, practical modes of administration, and development of
      formulations that maintain the viability of phages for administration. Also,
      meaningful evaluation of phage therapy will require animal studies that closely
      represent the intended use, and will include thorough investigation of the
      emergence and characteristics of phage resistant bacteria. As well, effective use
      will require understanding the ecology and dynamics of the endemic and
      therapeutic phages and their interactions with target bacteria in the farm
      environment. In the event that the potential of phage therapy is realized,
      adoption will depend on its efficacy and complementarity relative to other
      interventions. Another potential challenge will be regulatory approval.

PMID- 19102792
TI  - Probiotics, prebiotics and competitive exclusion for prophylaxis against
      bacterial disease.
AB  - The microbial population of the intestinal tract is a complex natural resource
      that can be utilized in an effort to reduce the impact of pathogenic bacteria
      that affect animal production and efficiency, as well as the safety of food
      products. Strategies have been devised to reduce the populations of food-borne
      pathogenic bacteria in animals at the on-farm stage. Many of these techniques
      rely on harnessing the natural competitive nature of bacteria to eliminate
      pathogens that negatively impact animal production or food safety. Thus feed
      products that are classified as probiotics, prebiotics and competitive exclusion
      cultures have been utilized as pathogen reduction strategies in food animals with
      varying degrees of success. The efficacy of these products is often due to
      specific microbial ecological factors that alter the competitive pressures
      experienced by the microbial population of the gut. A few products have been
      shown to be effective under field conditions and many have shown indications of
      effectiveness under experimental conditions and as a result probiotic products
      are widely used in all animal species and nearly all production systems. This
      review explores the ecology behind the efficacy of these products against
      pathogens found in food animals, including those that enter the food chain and
      impact human consumers.

PMID- 19102793
TI  - Is there a cost of parasites to caribou?
AB  - SUMMARY: Macroparasites potentially play a significant but often ignored role in
      the ecology and dynamics of wild ruminant populations. In the Arctic, parasites
      may impact on host populations by exacerbating the effects of seasonal and
      limited forage availability on the condition, fecundity and survival of
      individuals. We studied the effects of abomasal nematode parasites and warble
      flies, Hypoderma tarandi, on condition and pregnancy of caribou Rangifer tarandus
      in the Dolphin-Union herd, Nunavut, Canada. By the end of winter, female caribou
      over 2 years old showed a significant decrease in body weight with increasing
      nematode burden, and a decrease in back fat depth with increasing warble
      abundance. These effects were exaggerated in the non-pregnant fraction of the
      population. High warble larvae burdens were also associated with significantly
      reduced probability of being pregnant. Our research demonstrates a negative
      relationship between parasites and caribou condition that may have consequences
      for their fitness. Additionally, we discuss the possibility that muskox Ovibos
      moschatus share some parasite species with the caribou and could lead to elevated
      burdens in the sympatric host. Parasites may have been a contributory factor in a
      previous winter range-shift of the caribou herd and this may reflect a form of
      apparent competition between the two ungulate species.

PMID- 19102794
TI  - An anomaly against a current paradigm--extremely low rates of individual
      fecundity variability of the Gordian worm (Nematomorpha: Gordiida).
AB  - SUMMARY: Extreme variation in reproductive success (VRS) has been reported as a
      common feature of populations. Few individuals producing most of the offspring
      for the next generation has potential consequences for the population dynamics,
      genetics, and evolution of a group of organisms. High VRS has been described as a
      normal feature of helminth populations, although studies have focused largely on
      parasites of vertebrate hosts. Paragordius varius, a parasite of crickets, was
      used as a model system to study VRS. In this life cycle, worms absorb and store
      resources for reproduction from their hosts before being released into water. Egg
      output varied significantly with worm length, indicating that female length is an
      excellent predictor of fecundity. Analyses using the Lorenz curve and Gini
      coefficient suggest that there were no marked fecundity differences. This result
      was supported by data collected from a natural gordiid population, Gordius
      difficilis, suggesting that within gordiid populations the offspring of the next
      generation are contributed nearly equally by females. In addition, male body
      length appeared to be limited by intensity, whereas females showed no length
      limitation by crowding. These results contrast previous studies of parasites.

PMID- 19102795
TI  - Stimulus-reinforcement-based decision making and anxiety: impairment in
      generalized anxiety disorder (GAD) but not in generalized social phobia (GSP).
AB  - BACKGROUND: Generalized social phobia (GSP) involves the fear/avoidance of social
      situations whereas generalized anxiety disorder (GAD) involves an intrusive worry
      about everyday life circumstances. It remains unclear whether these, highly co
      morbid, conditions represent distinct disorders or alternative presentations of a
      single underlying pathology. In this study, we examined stimulus-reinforcement
      based decision making in GSP and GAD. METHOD: Twenty unmedicated patients with
      GSP, 16 unmedicated patients with GAD and 19 age-, IQ- and gender-matched healthy
      comparison (HC) individuals completed the Differential Reward/Punishment Learning
      Task (DRPLT). In this task, the subject chooses between two objects associated
      with different levels of reward or punishment. Thus, response choice indexes not
      only reward/punishment sensitivity but also sensitivity to reward/punishment
      level according to between-object reinforcement distance. RESULTS: We found that
      patients with GAD committed a significantly greater number of errors than both
      the patients with GSP and the HC individuals. By contrast, the patients with GSP
      and the HC individuals did not differ in performance on this task. CONCLUSIONS:
      These results link GAD with anomalous non-affective-based decision making. They
      also indicate that GSP and GAD are associated with distinct pathophysiologies.

PMID- 19102796
TI  - Prevalence and incidence of hepatitis C in injecting drug users attending
      genitourinary medicine clinics.
AB  - Surveillance reports and prevalence studies have indicated that injecting drug
      users (IDUs) contribute more to the hepatitis C epidemic in the United Kingdom
      than any other risk group. Information on both the prevalence and incidence of
      hepatitis C in IDUs is therefore essential to understanding the epidemiology of
      this infection. The prevalence of hepatitis C in specimens from the Unlinked
      Anonymous Prevalence Monitoring Programme collected in 1995, 1996, 1998, 1999,
      2000, and 2001 was determined using residual syphilis serology specimens from
      IDUs attending 15 genitourinary medicine (GUM) clinics in and outside London.
      These specimens were tested for antibodies to hepatitis C virus (anti-HCV). Using
      this cross-sectional design, anti-HCV-negative specimens were tested for HCV RNA
      to identify incident infections during the 'window' period of infection, and thus
      to estimate HCV incidence. Results of the multivariable analysis showed that
      there was marked variation in prevalence by clinic (P<0.0001) and age (P<0.0001).
      Overall the majority of infections were in males and the overall prevalence in
      injectors declined over the study period from 36.9% to 28.7%. The annual
      incidence in these injectors was estimated as being 3.01% (95% CI 1.25-6.73).
      Over the study period HCV incidence decreased by 1.2% per year. Genotyping of the
      incident infections identified the most common genotype as type 1 with type 3
      being more frequently seen after 1998. Of the prevalent infections, genotype 1
      was the most common. The study has confirmed a higher prevalence of anti-HCV in
      IDUs in the London area compared to those outside London. How representative of
      the current injecting drug user population are IDUs attending GUM clinics is
      unclear. Even so, such studies allow prevalence and incidence to be estimated in
      individuals who have ever injected drugs and inform ongoing public health
      surveillance.

PMID- 19102797
TI  - A comparison of hepatitis B seroepidemiology in ten European countries.
AB  - To inform current and future vaccination strategies, we describe the
      seroepidemiology of hepatitis B virus (HBV) infection in ten representative
      European countries using standardized serology that allowed international
      comparisons. Between 1996 and 2003, national serum banks were compiled by
      collecting residual sera or by community sampling; sera were then tested by each
      country using its preferred enzyme immunoassays and testing algorithm, and assay
      results were standardized. Information on current and past HBV vaccination
      programmes in each country was also collected. Of the ten countries, six reported
      low levels (<3%) of antibodies against HBV core antigen (anti-HBc). Of the eight
      countries testing for HBV surface antigen (HBsAg), the highest prevalence was
      reported in Romania (5.6%) and in the remaining seven countries prevalence was
      <1%. Universal HBV vaccination programmes had been established in seven countries
      as recommended by the World Health Organization, but the seroprevalence of
      antibodies against HBsAg (anti-HBs) was lower than the reported vaccine coverage
      in three countries. Regular serological surveys to ascertain HBV status within a
      population, such as reported here, provide important data to assess the need for
      and to evaluate universal HBV vaccination programmes.

PMID- 19102798
TI  - Dynamics of Legionella antibody levels during 1 year in a healthy population.
AB  - A total of 522 Danish blood donors were followed during 2004-2005 to describe the
      seroepidemiology of Legionella infections in healthy individuals from a general
      population. Antibodies to Legionella spp. were measured by indirect
      immunofluorescence antibody test. The prevalence of Legionella antibodies (titre
      1:128) was 26.8% and remained fairly constant during the year of follow-up.
      However, 6.9% of the blood donors developed a fourfold or greater rise in
      antibody titres. A history of visits to Danish summer cottages was associated
      with both Legionella seropositivity (OR 1.53, 95% CI 1.02-2.30) and
      seroconversion (OR 2.66, 95% CI 1.21-5.83). There were no consistent associations
      between either levels of antibody titres or seroconversion and self-reported
      health symptoms, absence from work due to illness, or to any risk factors. We
      conclude that community-acquired Legionella infections are frequent; however,
      they rarely result in severe illness.

PMID- 19102799
TI  - A national outbreak of verotoxin-producing Escherichia coli O157 associated with
      consumption of lemon-and-coriander chicken wraps from a supermarket chain.
AB  - A national outbreak of verotoxin-producing Escherichia coli O157 infection
      affected five English regions and Wales. Twelve cases were associated with lemon
      and-coriander chicken wrap from a single supermarket chain consumed over a 5-day
      period. An outbreak investigation aimed to identify the source of infection.
      Descriptive epidemiology and phenotypic and genotypic tests on human isolates
      indicated a point-source outbreak; a case-control study showed a very strong
      association between consumption of lemon-and-coriander chicken wrap from the
      single supermarket chain and being a case (OR 46.40, 95% CI 5.39-infinity,
      P=0.0002). Testing of raw ingredients, products and faecal samples from staff in
      the food production unit did not yield any positive results. The outbreak was
      probably caused by one contaminated batch of an ingredient in the chicken wrap.
      Even when current best practice is in place, ready-to-eat foods can still be a
      risk for widespread infection.

PMID- 19102800
TI  - Characteristics and diagnostic profile of patients seeking dementia care in a
      memory clinic in Hong Kong.
AB  - BACKGROUND: Seeking medical advice for dementia involves an understanding of
      norms, values and attitudes towards care-giving and inter-dependency, which are
      culturally bounded. We hypothesize that local culture and socioeconomic structure
      affect our Chinese patients who present with forgetfulness to our memory clinic.
      METHODS: A retrospective case notes review was undertaken on 454 consecutive
      patients referred to the memory clinic at Princess Margaret Hospital, Hong Kong.
      RESULTS: 385 patients were diagnosed with dementia and 27 had mild cognitive
      impairment. Reversible dementia was identified in 24 patients and normal
      cognition in 18. In patients with dementia, 55.8% had Alzheimer's disease, 26.2%
      had vascular dementia, 6.0% had other irreversible dementia, 5.2% had dementia
      with Lewy bodies, 4.9% had undetermined dementia and 1.8% had frontotemporal
      dementia. The median duration from symptom onset to medical consultation was two
      years; 66.5% had advanced disease with initial Mini-mental State Examination
      scores < or = 17. On their first visit, 85% of patients were living in the
      community; after two years this proportion had fallen to 63%. CONCLUSIONS:
      Dementia patients in Hong Kong apparently enjoy a long subclinical period and
      only seek medical attention at late stages. Local Chinese culture and
      socioeconomic backgrounds could be the main reasons that underlie these
      observations.

PMID- 19102801
TI  - Small, homelike care environments for older people with dementia: a literature
      review.
AB  - BACKGROUND: There is large cross-national variation in the characteristics of
      small, domestic-style care settings which emphasize normalized living. However, a
      systematic overview of existing types is lacking. This study provides an
      international comparison of the care concepts which have adopted a homelike
      philosophy in a small-scale context. Insight into their characteristics is vital
      for theory, planning and implementation of such dementia care settings. METHOD: A
      literature search was performed using various electronic databases, including
      PubMed, Medline, CINAHL and PsycINFO. In addition, "gray" literature was
      identified on the internet. Concepts were analyzed according to five main
      characteristics: physical setting, number of residents, residents'
      characteristics, domestic characteristics and care concept. RESULTS: 75 papers
      were included covering 11 different concept types in various countries.
      Similarities among concepts reflected a focus on meaningful activities centered
      around the daily household. Staff have integrated tasks and are part of the
      household, and archetypical home-style features, such as kitchens, are
      incorporated in the buildings. Differences among concepts were found mainly in
      the physical settings, numbers of residents and residents' characteristics. Some
      concepts have become regular dementia care settings, while others are smaller
      initiatives. CONCLUSION: The care concepts are implemented in various ways with a
      changing staff role. However, many aspects of these small, homelike facilities
      remain unclear. Future research is needed, focusing on residents'
      characteristics, family, staff and costs.

PMID- 19102802
TI  - Clinical experiences of patients with catecholaminergic polymorphic ventricular
      tachycardia.
AB  - Catecholaminergic polymorphic ventricular tachycardia is a rare entity that can
      occur in children without cardiac disease and with a normal QT interval. It may
      cause syncope, convulsions, and sudden death during physical activity or
      emotional distress. We report the clinical features, treatment, and follow-up of
      16 children with this diagnosis, emphasizing the potentially fatal nature of the
      disease.The mean age of patients at the onset of symptoms and at the time of
      diagnosis was 7.8 plus or minus 2.5 years, and 10.6 plus or minus 3.5 years,
      respectively. Syncope was the main complaint in 11, and 7 were treated as
      erroneously as having epilepsy. Diagnosis was confirmed by exercise and/or
      infusion of isoproterenol. Once the diagnosis was made, we started propranolol in
      all patients, and added verapamil if ventricular tachycardia was still inducible
      on a treadmill exercise test. An intracardiac defibrillator was implanted in 4
      patients. Of the 16 patients, 4 died suddenly, giving a rate of mortality of 25%.
      In 2 of those dying suddenly, there was evidence of poor compliance to the
      recommended treatment. Another 2 patients had been resuscitated because of sudden
      cardiac arrest.Catecholaminergic polymorphic ventricular tachycardia must be
      considered in the differential diagnosis of syncope in children without heart
      disease but with a normal QT interval. Medical treatment with propranolol and
      verapamil may decrease the incidence of arrhythmia. Implantation of intracardiac
      defibrillators should be considered in those resistant to drug therapy. Delay in
      diagnosis, and inadequate treatment, can result in sudden cardiac death.

PMID- 19102803
TI  - Education, and obtaining of informed consent, using multimedia before adults with
      congenitally malformed hearts are submitted to transcatheter interventions.
AB  - BACKGROUND: Multimedia programmes relating to education and consents may be
      useful for decreasing anxiety during catheter-based repair in patients with
      congenitally malformed hearts. OBJECTIVE: Our study was aimed at evaluating the
      impact of multimedia protocols for education of a population of consecutive
      patients with congenitally malformed hearts prior to transcatheter repair.
      METHODS: Between September, 2006, and May, 2008, we enrolled 100 consecutive
      patients, with a mean age of 45 +/- 19 years, of whom 69 were female, for
      catheter-based repair of their congenitally malformed hearts. In the first 50
      patients, we used a written form for informed consent sent to the patients 15
      days before the procedure, coupled with a personal interview of 30 minutes. In
      the subsequent 50 patients, we used multimedia protocol for education, comprising
      a booklet of 4 pages containing a simple and brief explanation of the
      intervention, and a digital film of 4 minutes showing the transcatheter procedure
      with a commentary provided by the referring physician, prior to obtaining the
      signature for informed consent. We then compared the scores for anxiety, the pre
      operative heart rate, the frequency of vaso-vagal episodes, and the need for
      conscious sedation between the two groups. RESULTS: Patients who underwent
      preconditioning using the multimedia programme were significantly less anxious,
      and had significantly lower heart rates. Vaso-vagal episodes were also
      significantly less in this group, with no episodes compared to 14% in those
      providing standard informed consent. Conscious sedation was needed more
      frequently in those providing standard informed consent. CONCLUSION: Our brief
      study suggests that a comprehensive multimedia programme of preparation increases
      the tolerability, and decrease the emotional state, of adults about to undergo
      catheter-based interventions for congenital cardiac disease.

PMID- 19102804
TI  - Shwachman-Diamond syndrome: implications for understanding the molecular basis of
      leukaemia.
AB  - Inherited bone marrow failure syndromes provide extremely useful genetic models
      for understanding leukaemogenesis because the initial genetic defect can be
      identified and the risk of leukaemia is very high. Shwachman-Diamond syndrome is
      one of the most common inherited bone marrow failure syndromes and an example of
      such a model. Here, I describe the malignant features of Shwachman-Diamond
      syndrome and discuss the potential molecular mechanisms that can lead to
      leukaemia.

PMID- 19102805
TI  - The well-being of children in food-insecure households: results from The Eastern
      Caribbean Child Vulnerability Study 2005.
AB  - OBJECTIVE: To examine the relationship between food insecurity and child well
      being indicators. DESIGN: Cross-sectional survey conducted in 2344 households
      with children. The main exposure measure was food insecurity status, which was
      categorized as food secure or food insecure based on two or more food insecurity
      questions answered in the affirmative. Multiple logistic regression analysis was
      used to model the association between food insecurity status and selected child
      well-being indicators. SETTING: Barbados, St. Lucia and St. Vincent and the
      Grenadines (hereafter St. Vincent), three Eastern Caribbean countries, 2005.
      SUBJECTS: A random sample of households with children was identified by the
      governments of Barbados, St. Lucia and St. Vincent. In-home interviews were
      conducted by social workers. RESULTS: One-third (33%) of households were
      categorized as food insecure. Food-insecure households were more likely to
      include a chronically ill parent (OR = 2.48; 95% CI 1.76, 3.49), a recently
      divorced parent (OR = 1.92; 95% CI 1.21, 3.05), a child requiring multiple visits
      to a health-care provider for a disability (OR = 3.98; 95% CI 1.20, 13.19) or
      injury (OR = 1.78; 95% CI 1.12, 2.83), a child with a learning disability (OR =
      2.08; 95% CI 1.16, 3.74) or a child with a physical disability (OR = 2.54; 95% CI
      1.22, 5.32) after adjustment for poverty and other demographic variables.
      CONCLUSIONS: The results indicate that food-insecure households were more likely
      to be burdened by child disability (learning and physical), family system
      disruption (recent divorce and chronic illness) and child health-care needs (for
      disability and injury) than food-secure households. The implementation of
      programmes and policies to minimize food insecurity in the Eastern Caribbean may
      be warranted.

PMID- 19102806
TI  - Monetary cost of dietary energy is negatively associated with BMI and waist
      circumference, but not with other metabolic risk factors, in young Japanese
      women.
AB  - OBJECTIVE: Little is known about the relationship of dietary cost to health
      status. The present cross-sectional study examined the association between the
      monetary cost of dietary energy (Japanese yen/4184 kJ) and several metabolic risk
      factors. DESIGN: Monetary cost of dietary energy was estimated based on dietary
      intake assessed by a self-administered diet history questionnaire and retail food
      prices. Body height and weight, from which BMI was derived, waist circumference
      and blood pressure were measured and fasting blood samples were collected for
      biochemical measurements. SETTING: A total of fifteen universities and colleges
      in Japan. SUBJECTS: A total of 1136 female Japanese dietetic students aged 18-22
      years. RESULTS: After adjustment for potential confounding factors, monetary cost
      of dietary energy was significantly and negatively associated with BMI (P for
      trend = 0.0024). Monetary cost of dietary energy also showed a significant and
      negative association with waist circumference independently of potential
      confounding factors, including BMI (P for trend = 0.0003). No significant
      associations were observed for other metabolic risk factors examined (P for trend
      = 0.10-0.88). CONCLUSIONS: The monetary cost of dietary energy was independently
      and negatively associated with both BMI and waist circumference, but not other
      metabolic risk factors, in a group of young Japanese women.

PMID- 19102807
TI  - Downward trends in the prevalence of childhood overweight in the setting of 12
      year school- and community-based programmes.
AB  - OBJECTIVE: A school-based nutrition information programme was initiated in 1992
      in two towns in northern France (Fleurbaix and Laventie, FL) and was followed by
      a number of community-based interventions. We took the opportunity to measure the
      outcomes in terms of childhood obesity and overweight over the next 12 years.
      DESIGN: Repeated, cross-sectional, school-based survey. For the school years
      beginning in 1992, 2000, 2002, 2003 and 2004, the height and weight of all 5- to
      12-year-old children attending school were measured in FL. In 2004, the same
      assessments were made in two comparison towns with similar socio-economic
      characteristics but no intervention. SETTING: Fleurbaix and Laventie
      (intervention towns), Bois-Grenier and Violaines (comparison towns), northern
      France. SUBJECTS: In 2002, 2003 and 2004, respectively 515, 592 and 633 children
      were measured in FL (participation rate of 95-98% of all eligible individuals);
      in the comparison towns, 349 children were measured in the 2004 school year (98%
      of the towns' school population). RESULTS: After an initial increase, trends in
      mean BMI and prevalence of overweight started to reverse. Compared with 2002, the
      age-adjusted OR for overweight in FL was significantly lower in 2003 and 2004
      (but for girls only). In the 2004 school year, the overweight prevalence was
      significantly lower in FL (8.8%) than in the comparison towns (17.8%, P <
      0.0001). CONCLUSION: These data suggest that, over a long period of time,
      interventions targeting a variety of population groups can have synergistic
      effects on overweight prevalence. This gives hope that it is possible to reverse
      trends towards increasing overweight by actions at the community level.

PMID- 19102808
TI  - Two-year controlled effectiveness trial of a school-based intervention to prevent
      obesity in Chilean children.
AB  - OBJECTIVE: Obesity prevalence among Chilean children is 19.4%. The present study
      aimed to assess the effectiveness of a school-based obesity prevention programme.
      DESIGN: Non-randomized controlled study. The intervention included activities in
      nutrition and physical activity, fully applied the first year and partially in
      the second one. Primary outcomes were BMI Z-score (BMIZ) and obesity prevalence;
      secondary outcomes were waist circumference and triceps skinfold thickness. Time
      effects were assessed by changes in BMI-related variables by gender and period
      (ANOVA and Tukey test), while intervention effects were determined by comparing
      changes in (i) obesity prevalence by gender and period (PROC GENMOD) and (ii)
      BMIZ according gender, age and period (PROC MIXED). SETTING: Primary schools in
      the Chilean cities of Casablanca (intervention group) and Quillota (control
      group). SUBJECTS: One thousand seven hundred and fifty-nine children from three
      schools (intervention group) and 671 from one school (control group). RESULTS:
      Over the two years, obesity prevalence and BMIZ declined significantly in the
      intervention group; from 17.0% to 12.3% and 14.1% to 10.3% in boys and girls,
      respectively, and from 0.62 to 0.53 and 0.64 to 0.58, respectively. In the
      control group, obesity remained stable at about 21% and 15%, while BMIZ increased
      significantly in the second year. BMIZ declined in both genders and all age
      categories in the intervention group during the first year (significant only in
      younger boys). No changes occurred during the summer, while during the second
      year, BMIZ increased in boys and girls from both groups (significant only in the
      younger control boys). Obesity declined significantly only in boys during the
      first year. CONCLUSION: Effectiveness was greater in the first school year and
      more evident in younger boys.

PMID- 19102809
TI  - Social mobilization and social marketing to promote NaFeEDTA-fortified soya sauce
      in an iron-deficient population through a public-private partnership.
AB  - OBJECTIVE: The present pilot project aimed to assess the effectiveness of social
      mobilization and social marketing in improving knowledge, attitudes and practices
      (KAP) and Fe status in an Fe-deficient population. DESIGN: In an uncontrolled,
      before-after, community-based study, social mobilization and social marketing
      strategies were applied. The main outcomes included KAP and Hb level and were
      measured at baseline, 1 year later and 2 years later. SETTING: One urban county
      and two rural counties in Shijiazhuang Municipality, Hebei Province, China.
      SUBJECTS: Adult women older than 20 years of age and young children aged from 3
      to 7 years were selected from three counties to attend the evaluation protocol.
      RESULTS: After 1 year, most knowledge and attitudes had changed positively
      towards the prevention and control of anaemia. The percentage of women who had
      adopted NaFeEDTA-fortified soya sauce increased from 8.9% to 36.6% (P < or =
      0.001). After 2 years, Hb levels had increased substantially, by 9.0 g/l (P < or
      = 0.001) in adult women and 7.7 g/l (P < or = 0.001) in young children.
      CONCLUSION: Social mobilization and social marketing activities had a positive
      impact on the KAP of adult women, and resulted in marked improvements in Hb
      levels in both adult women and young children. This should be recommended as a
      national preventive strategy to prevent and control Fe deficiency and Fe
      deficiency anaemia.

PMID- 19102810
TI  - Validation of an FFQ for evaluation of EPA and DHA intake.
AB  - OBJECTIVE: To validate an FFQ for the assessment of dietary EPA and DHA against
      their relative concentrations in red blood cells (RBC). DESIGN: Cross-sectional
      analysis of baseline data. Intakes of marine food products and EPA and DHA were
      estimated by FFQ on the basis of consumption of marine food products in the last
      month. Fatty acid composition of RBC membranes was quantified by GC. SETTING:
      Saint-Francois d'Assise Hospital, Quebec, Canada. SUBJECTS: A total of sixty-five
      middle-aged women who participated in a randomized clinical trial. RESULTS:
      Spearman's correlation coefficient between intake of EPA, DHA and EPA + DHA and
      their corresponding concentration in RBC was 0.46, 0.40 and 0.42, respectively
      (all P < 0.05). Multiple regression analysis of EPA+DHA intake and RBC EPA + DHA
      concentration indicated positive and significant correlations for oily fish (beta
      = 0.44, 95% CI 0.16, 0.72, P = 0.0027), total fish (beta = 0.42, 95% CI 0.19,
      0.64, P = 0.0005) and marine food products (beta = 0.42, 95% CI 0.20, 0.64, P =
      0.0003). No other marine food products significantly predicted RBC EPA + DHA
      concentration. CONCLUSIONS: Although the present validation study was undertaken
      among middle-aged women with low consumption of marine food products (<3
      servings/week), our FFQ provided estimates of EPA and DHA intakes that correlated
      fairly well with their RBC concentrations. However, the absence of correlations
      between EPA + DHA intakes from different marine species suggests that a minimum
      EPA + DHA intake is necessary to observe a relationship with RBC EPA + DHA
      concentrations.

PMID- 19102811
TI  - Iron bioavailability of cocoa powder as determined by the Hb regeneration
      efficiency method.
AB  - Fe deficiency is a public-health problem worldwide, and effective measures for
      preventing Fe deficiency are needed. The aim of the present study was to
      determine the bioavailability of Fe in cocoa using the Hb regeneration efficiency
      (HRE) method. Thirty-five F344/N male weanling rats were fed a low-Fe diet for 4
      weeks to deplete body Fe stores. Then, four groups of seven animals each were
      repleted for 20 d using a modified AIN-93G diet fortified with ferrous sulphate,
      ferric citrate or two brands of cocoa powder to provide a total dietary Fe
      concentration of 20 mg/kg. As a negative control, seven rats were maintained on
      the low-Fe diet. The HRE were 0.733, 0.350, 0.357 and 0.336 for ferrous sulphate,
      ferric citrate and the two brands of cocoa powder, respectively. The relative
      biological values (RBV), defined as the ratio of the sample HRE to that of
      ferrous sulphate, were 0.478, 0.488 and 0.459 for ferric citrate and the two
      brands of cocoa powder, respectively. The Fe bioavailability of cocoa was
      significantly less than that of ferrous sulphate and was similar to that of
      ferric citrate. The difference in Fe bioavailability between the two brands of
      cocoa powder was negligible. When the negative control was used to correct the
      data, estimates of the RBV derived from Hb gain were similar to those derived
      from the HRE. These results suggest that cocoa is a significant source of
      moderately bioavailable Fe.

PMID- 19102812
TI  - An evaluation of antigen B family of Echinococcus granulosus, its conformational
      propensity and elucidation of the agretope.
AB  - The present communication evaluates the antigen B (AgB) family of bubaline
      isolates of Echinococcus granulosus with respect to their conformational
      propensity and also discusses the stretches of agretope. AgB, which is abundantly
      present in hydatid cyst fluid, is encoded by a gene family, AgB1-AgB5.
      Hydatidosis is of zoonotic and economic importance in India. Buffaloes serve as
      the intermediate host. However, to date the AgB family has not been fully
      analysed. During the present study two different primers used for amplification
      of AgB1 revealed homology to Echinococcus canadensis (G8) as well as E.
      granulosus sensu stricto (G1/G2). The sequence of AgB3 is homologous to that of
      the well-defined species, Echinococcus ortleppi (G5), and the predicted amino
      acid sequence of AgB4 is homologous to bovine isolates identified earlier. alpha-
      and beta-amphipathic structures were recorded in all the antigens designated as T
      cell receptor sites. The antigenic index of different stretches correlated with
      hydrophilicity because the hydrophobic residues are not accessible to the cells.
      In this study, we investigated the binding propensity of AgB to MHC II in order
      to determine stretches of agretope. Agretopes began with four hydrophilic
      residues. Two to three additional hydrophilic residues were present in the
      internal motif. This comparison of AgB and its family of bubaline isolates, with
      respect to their sequence information, alpha- and beta- amphipathic regions,
      antigenic index and stretches of agretope is the first such report from India.

PMID- 19102813
TI  - Effects of methodological variation on assessment of riboflavin status using the
      erythrocyte glutathione reductase activation coefficient assay.
AB  - Riboflavin status is usually measured as the in vitro stimulation with flavin
      adenine dinucleotide of the erythrocyte enzyme glutathione reductase, and
      expressed as an erythrocyte glutathione reductase activation coefficient (EGRAC).
      This method is used for the National Diet and Nutrition Surveys (NDNS) of the UK.
      In the period between the 1990 and 2003 surveys of UK adults, the estimated
      prevalence of riboflavin deficiency, expressed as an EGRAC value > or = 1.30,
      increased from 2 to 46 % in males and from 1 to 34 % in females. We hypothesised
      that subtle but important differences in the detail of the methodology between
      the two NDNS accounted for this difference. We carried out an evaluation of the
      performance of the methods used in the two NDNS and compared against an 'in
      house' method, using blood samples collected from a riboflavin intervention
      study. Results indicated that the method used for the 1990 NDNS gave a
      significantly lower mean EGRAC value than both the 2003 NDNS method and the 'in
      house' method (P < 0.0001). The key differences between the methods relate to the
      concentration of FAD used in the assay and the duration of the period of
      incubation of FAD with enzyme. The details of the EGRAC method should be
      standardised for use in different laboratories and over time. Additionally, it is
      proposed that consideration be given to re-evaluating the basis of the EGRAC
      threshold for riboflavin deficiency.

PMID- 19102814
TI  - Lichen sclerosis et atrophicus masquerading as tonsillar squamous cell carcinoma.
AB  - OBJECTIVE: We report a case of a 70-year-old man of Asian origin with lichen
      sclerosus et atrophicus affecting the tonsil, which presented as a painful,
      enlarging, exophytic lesion mimicking squamous cell carcinoma. METHOD: We present
      a case report and a review of the world literature regarding lichen sclerosus et
      atrophicus. RESULTS: Lichen sclerosus is a chronic, benign, inflammatory
      dermatosis of the skin and mucous membranes which mostly affects the female
      genitalia, presenting as white plaques with epidermal atrophy. The cause is
      unknown, although a number of aetiologies have been proposed. The prevalence is
      unknown. Women have been reported to be affected six to 10 times more than men,
      and the condition has no known racial preference. CONCLUSION: Our patient
      illustrates a rare case of the condition lichen sclerosus et atrophicus; to our
      knowledge, this case represents the first report of tonsillar involvement of the
      condition. The case presented a diagnostic challenge.

PMID- 19102815
TI  - Patulous eustachian tube complicating gastric bypass surgery.
AB  - OBJECTIVE: We report the first case in the English literature of a patulous
      eustachian tube occurring after laparoscopic Roux-en-Y gastric bypass surgery for
      obesity. METHOD: Case report of a 44-year-old woman who was referred to our ENT
      clinic complaining of autophonia and bilateral aural fullness. The patient had
      noticed these symptoms after she had undergone a laparoscopic Roux-en-Y gastric
      bypass surgery to aid weight loss. RESULT: On the basis of the medical history,
      clinical examination and immittance measurement (revealing a change in acoustic
      immittance synchronous with normal breathing in the right ear), a diagnosis of
      patulous eustachian tube was made, more severe in the right ear than the left.
      CONCLUSION: We report a case of patulous eustachian tube occurring after
      laparoscopic gastric bypass surgery for weight loss, which could be considered as
      one of the possible complications of this surgery. Our patient began to notice
      the symptoms of patulous eustachian tube after a 20 kg weight loss.

PMID- 19102817
TI  - Towards a theory of intentional behaviour change: plans, planning, and self
      regulation.
AB  - PURPOSE: Briefly review the current state of theorizing about volitional
      behaviour change and identification of challenges and possible solutions for
      future theory development. METHOD: Review of the literature and theoretical
      analysis. RESULTS: Reasoned action theories have made limited contributions to
      the science of behaviour change as they do not propose means of changing
      cognitions or account for existing effective behaviour change techniques.
      Changing beliefs does not guarantee behaviour change. The implementation
      intentions (IMPs) approach to planning has advanced theorizing but the
      applications to health behaviours often divert substantially from the IMPs
      paradigm with regard to interventions, effects, mediators and moderators. Better
      construct definitions and differentiations are needed to make further progress in
      integrating theory and understanding behaviour change. CONCLUSIONS: Further
      progress in theorizing can be achieved by (a) disentangling planning constructs
      to study their independent and joint effects on behaviour, (b) progressing
      research on moderators and mediators of planning effects outside the laboratory
      and (c) integrating planning processes within learning theory and self-regulation
      theory.

PMID- 19102816
TI  - Gene expression in the anterior cingulate cortex and amygdala of adolescent
      marmoset monkeys following parental separations in infancy.
AB  - Early life adversities are risk factors for later mood and emotional disorders.
      Repeated separation of infant marmosets from their parents provides a validated
      primate model of depression vulnerability, producing in-vivo biochemical and
      behavioural effects indicative of persistently altered stress reactivity and mild
      anhedonia. Here we report the long-term effect (in adolescence) of this
      intervention on the expression of synaptophysin, GAP-43, VGluT1, VGAT, MAP-2,
      spinophilin, and 5-HT1A and 5-HT2A receptors, in the anterior cingulate cortex
      (ACC; supragenual and subgenual areas) and amygdala (lateral, basal and central
      nuclei). These genes and regions are implicated in the response to stress or in
      mood disorder. The profile of 5-HT1A receptor binding in ACC was affected by
      early deprivation, notably in the subgenual region, with a decrease in deep
      laminae but an increase in superficial laminae. Following early deprivation,
      spinophilin mRNA was reduced in subgenual ACC. In the amygdala, no significant
      effects of the manipulation were seen, but expression of several transcripts was
      sexually dimorphic. There were correlations between expression of some
      transcripts and in-vivo measurements. The results show that early deprivation in
      a non-human primate has a selective long-term effect on expression of genes in
      the ACC, particularly the subgenual area. The results differ from those reported
      in the hippocampus of the same animals, indicating the presence of limbic region
      specific long-term molecular responses to early life stress.

PMID- 19102818
TI  - Long-term outcome of continuous ambulatory peritoneal dialysis (CAPD)
      peritonitis: surgery can be avoided.
AB  - INTRODUCTION: Continuous ambulatory peritoneal dialysis (CAPD) has become the
      preferred method of home dialysis for patients with end-stage renal failure.
      Peritonitis is a common and serious complication and requires prompt diagnosis
      and treatment. The aim of this study was to assess what proportion of patients
      with CAPD peritonitis that required surgical intervention for on-going sepsis or
      for peritonitis-related bowel obstruction. PATIENTS AND METHODS: All patients
      presenting with a first episode of CAPD peritonitis during the 5-year period from
      1994-1998 were identified from a prospectively maintained database. Data
      collected included patient demographics, details of peritonitis episodes and
      their treatment, and details of any surgical intervention undertaken. RESULTS: A
      total of 500 episodes were identified in 168 patients of whom 162 had complete
      follow-up representing 488 peritonitis episodes. Sixty-three patients experienced
      one episode of peritonitis, 33 two episodes, 20 had three episodes, and 46 had
      more than three episodes. None of the patients underwent surgery either primarily
      or for complications of the infective episode. A total of 465 episodes were due
      to a single organism (95%) and the remainder were due to multiple organisms (5%).
      The most common causative organisms were Gram-positive cocci (308 episodes; 71%)
      followed by Gram-negative bacilli (106 episodes; 24%). In 55 patients (34%), the
      same organism was implicated in consecutive admissions. Patients with autosomal
      dominant polycystic kidney disease (ADPKD), whilst accounting for 12 of 169 (7%)
      patients in the cohort, experienced 23 of 125 (18.4%) episodes of peritonitis by
      Gram-negative cocci. Such infections were seen in 8 of 12 (66.7%) ADPKD patients
      and accounted for 23 of 40 (57.5%) infections experienced by the ADPKD patients.
      CONCLUSIONS: Whilst CAPD peritonitis is a common problem in the renal failure
      population, with almost 100 episodes per year, it would appear that most episodes
      can be managed using intraperitoneal antibiotics without the need for surgical
      intervention.

PMID- 19102819
TI  - Referral letters for 2-week wait suspected colorectal cancer do not allow a
      'straight-to-test' pathway.
AB  - INTRODUCTION: Some clinicians have argued that 2-week wait suspected colorectal
      cancer patients can go 'straight-to-test' to facilitate time to diagnosis and
      treatment. The aim of this study was to evaluate whether the currently used
      referral letters are reliable enough to allow that pathway. PATIENTS AND METHODS:
      General practitioner (GP) letters referring patients under the Two Week-Wait Rule
      for suspected colorectal cancer were prospectively reviewed over a 6-month
      period. Three examining consultants were asked to outline the tests they would
      perform having only read the letter, and then again after a clinical consultation
      with the patient. The outcome of these tests was tracked. RESULTS: A total of 217
      referral letters of patients referred under Two Week Wait Rule for suspected
      colorectal cancer were studied. Having just read the referral letter, the most
      frequently requested test was colonoscopy (148), then CT scan (48), barium enema
      (44), followed by gastroscopy (23) and flexible sigmoidoscopy in 15 patients
      (some patients would have had more than one test requested). After consultation
      with the patients, tests requested as guided by the GP letter were changed in 67
      patients (31%), where 142 colonoscopies, 61 CT scans, 37 barium enemas, 23
      flexible sigmoidoscopies and 19 gastroscopies were organised. The referral
      indication which had tests changed most often was definite palpable rectal mass
      (67%), while patients referred with definite palpable right-sided abdominal mass
      had their tests least often changed (9%). A total of 22 patients were found to
      have colorectal cancers (10%) and 30 patients were diagnosed with polyps (14%).
      Out of 142 colonoscopies performed, 19 (13%) showed some pathology beyond the
      sigmoid colon and of the 23 patients who had flexible sigmoidoscopy initially,
      only three went on to have colonoscopy subsequently. During the 6-month period of
      the study, only five breaches of the waiting time targets were recorded (1 to the
      31-day target and 4 to the 62-day target). CONCLUSIONS: A significant number of
      patients would have had tests changed after a clinical consultation. However,
      only a small number required further investigations having had a consultation
      prior to their initial investigations. We conclude that 2-week wait suspected
      colorectal cancer patients should be seen in the clinic first and should not
      proceed 'straight-to-test'.

PMID- 19102820
TI  - Sending NHS patients for operations abroad: is the holiday over?
AB  - INTRODUCTION: The UK Department of Health, in its attempt to help NHS trusts
      reduce long elective waiting lists, set up the overseas commissioning scheme in
      2002. This allowed hospitals to send their patients abroad for their surgery. In
      theory, this was a win-win situation, where pressures upon surgeons were reduced,
      and trusts could reach UK Government targets and avoid breaches. At our hospital,
      a significant number of patients, who had undergone a total joint replacement
      abroad, were discharged after only one postoperative review and often had very
      little physiotherapy. A few presented to our clinic with more serious problems.
      PATIENTS AND METHODS: This is a retrospective review of two matched groups of
      patients (22 each), all of whom underwent a total knee replacement in 2003. The
      first group (abroad, Belgium) included 10 males and 12 females with a mean age of
      74.5 years and a mean follow-up of 37 months. The second group (local
      institution) included 10 males and 12 females with a mean age of 71.4 years and a
      mean follow-up of 34 months. All patients were evaluated using the Oxford Knee
      Score (OKS), Knee Society Score (KSS), and SF-12 systems. RESULTS: OKS and KSS
      were similar in the two groups. However, SF-12 figures revealed a statistically
      significant difference in both the physical (PCS) and mental components (MCS).
      Belgium group - mean PCS 40, mean MCS 48: local group - mean PCS 47, mean MCS 57;
      P < 0.05. CONCLUSIONS: The results demonstrate that, although the majority of
      patients operated upon abroad got comparable functional results to patients
      operated locally, they often felt dissatisfied with the overall experience of
      travelling for their operation. Furthermore, the issues of 'patient ownership'
      and long-term follow-up need to be fully addressed in order to safeguard the high
      standard of care we should offer our patients.

PMID- 19102821
TI  - Consent for non-therapeutic male circumcision on religious grounds.
AB  - INTRODUCTION: The aim of this study was to assess whether surgeons are conforming
      to guidance laid down by professional organisations and the courts in obtaining
      dual parental consent for non-therapeutic circumcision. PATIENTS AND METHODS: A
      retrospective case-note review over a 12-month period (April 2005 to April 2006)
      of circumcisions in boys under the age of 16 years in a tertiary paediatric
      surgical unit was undertaken. RESULTS: A total of 62 boys aged 1-14 years (median
      age, 4 years) underwent non-therapeutic circumcision. Written consent from both
      parents was obtained in only 4 cases (6.4%). In no case was written consent
      obtained from the patient or their views documented. In 58 cases, the written
      consent was provided by only one parent; the mother in 34 (55%), the father in 24
      (45%). Of these 58 cases, in 25 (43%) both parents attended with the child on the
      day of surgery. CONCLUSIONS: The data reveal a consistent non-conformity with
      recommended practice and the common law. It seems unlikely that the doctors
      involved are deliberate and inveterate law-breakers. The reason for this non
      compliance may be ignorance of the rules, or due to the impracticality of their
      implementation. There is evidence that doctors are ignorant of the legal rules
      pertaining to their patients, and the results may reflect this ignorance.
      However, there are also practical difficulties in obtaining dual consent that may
      be partially responsible for the variance. Inevitably, investment will be
      required to overcome these difficulties. Cost may tempt service providers to
      abandon the provision, leaving parents to their own devices.

PMID- 19102823
TI  - Cost minimisation using clinic-based treatment for common hand conditions--a
      prospective economic analysis.
AB  - INTRODUCTION: The purpose of this study was to compare the cost of treatment of
      Dupuytren's disease, ganglia and trigger digits in the out-patient department
      with the operating theatre. PATIENTS AND METHODS: All patients seen in a new
      patient hand clinic with a diagnosis of Dupuytren's disease, trigger digit or
      ganglion of the wrist or hand requiring treatment were prospectively identified
      over a 6-month period. The numbers undergoing a procedure in the out-patient
      clinic or theatre were recorded. Costings of theatre time and out-patient time,
      as well as national tariff income, were obtained from the hospital management.
      RESULTS: Over the 6-month period, 80, 26, and 52 patients were treated with
      regard to Dupuytren's disease, ganglia and trigger digits, respectively. Of
      these, 37, 23, and 44 were treated by an out-patient procedure, and 43, 3 and 8
      underwent a formal operation. The total cost of the out-patient procedures was
      calculated at pound 1560 over 6 months. To perform these as formal operations
      would have cost pound 64,896. The cost savings were, therefore, pound 63,336, or
      pound 126,672 per annum. CONCLUSIONS: Out-patient interventions for Dupuytren's
      disease, ganglia and trigger digits result in significant cost savings over
      formal surgical treatment.

PMID- 19102825
TI  - Improving operation notes to meet British Orthopaedic Association guidelines.
AB  - INTRODUCTION: Operation notes are an important part of medical records for
      clinical, academic and medicolegal reasons. This study audited the quality of
      operative note keeping for total knee replacements against the standards set by
      the British Orthopaedic Association (BOA). PATIENTS AND METHODS: A prospective
      review of all patients undergoing total knee replacement at a district general
      hospital over 8 months. Data recorded were compared with those required by the
      BOA good-practice guidelines. Change in practice was implemented and the audit
      cycle completed. Data were statistically analysed. RESULTS: A total of 129
      operation notes were reviewed. There was a significant improvement in the mean
      number of data points recorded from 9.6 to 13.1. The least well recorded data
      were diagnosis, description of findings, alignment and postoperative flexion
      range. All had a significant improvement except description of findings. The
      operating surgeon writing the note improved from 56% to 67%. Detailed
      postoperative instructions also improved in quality. CONCLUSIONS: Surgeon
      education and the use of a checklist produce better quality total knee
      replacement operation notes in line with BOA guidelines. Further improvements may
      be made by making the data points part of the operation note itself.

PMID- 19102824
TI  - Do scoring systems help in predicting survival following ruptured abdominal
      aortic aneurysm surgery?
AB  - INTRODUCTION: The aim of this study was to assess the value of the Hardman Index
      and the Glasgow Aneurysm Score in predicting postoperative mortality in patients
      with ruptured abdominal aortic aneurysm (rAAA), and to assess the correlation
      between the two. PATIENTS AND METHODS: Patients admitted with rAAA were
      identified from a hospital database. Hospital records were reviewed and a
      retrospective Hardman Index and Glasgow Aneurysm Score was calculated. Poor
      postoperative prognosis was considered at a Glasgow Aneurysm Score > 95 or a
      Hardman Index >or= 3. RESULTS: A total of 96 patients with a median age of 77.5
      years (interquartile range, 71-83 years) and a male:female ratio of 2:1 were
      identified. Of these, 37 patients were not offered surgery and this was
      associated with 100% mortality. Of the 59 operated patients, 36 (61%) patients
      died postoperatively. Operated patients had a median Glasgow Aneurysm Score of 91
      (interquartile range, 77-101) and a Hardman Index of 2 (interquartile range, 1
      2). In this group, a Glasgow Aneurysm Score > 95 or a Hardman Index >or= 3 was
      not associated with mortality (P = 0.10 and P = 0.79, respectively). Correlation
      between the scoring systems was poor (+0.42 tau(b)). CONCLUSIONS: The scoring
      systems assessed did not help predict the outcome of rAAA surgery, and correlated
      poorly with each other. They do not aid clinical judgement.

PMID- 19102826
TI  - Ear, nose and throat day-case surgery at a district general hospital.
AB  - INTRODUCTION: In 2000, The NHS Plan in the UK set a target of 75% for all
      surgical activity to be performed as day-cases. We aim to assess day-case
      turnover for ENT procedures and, in particular, day-case rates for adult and
      paediatric otological procedures together with re-admissions within 72 h as a
      proxy measure of safety. PATIENTS AND METHODS: Retrospective collection of data
      (procedure and length of stay) from the computerised theatre system (Galaxy) and
      Patient Information Management System (PIMS) of all elective patients operated
      over one calendar year. The setting was a district general hospital ENT
      department in South East England. All ENT operations are performed with the
      exception of oncological head and neck procedures and complex skull-base surgery.
      RESULTS: Overall, 2538 elective operations were performed during the study
      period. A total of 1535 elective adult procedures were performed with 74% (1137
      of 1535) performed as day-cases. Of 1003 paediatric operations, 73% (730 of 1003)
      were day-cases. Concerning otological procedures, 93.4% (311 of 333) of
      paediatric procedures were day-cases. For adults, we divided the procedures into
      major and minor, achieving day-case rates of 88% (93 of 101) and 91% (85 of 93),
      respectively. The overall day-case rate for otological procedures was 91% (528 of
      580). Re-admission rates overall were 0.7% (11 of 1535) for adults and 0.9% (9 of
      1003) for paediatric procedures. The most common procedure for re-admission was
      tonsillectomy accounting for 56% of all adult re-admissions and 78% of paediatric
      re-admissions. The were no deaths following day-case procedures. DISCUSSION: ENT
      surgery is well-suited to a day-case approach. UK Government targets are
      attainable when considering routine ENT surgery. Day-case rates for otology in
      excess of targets are possible even when considering major ear surgery.

PMID- 19102827
TI  - White cell count and C-reactive protein measurement in patients with possible
      appendicitis.
AB  - INTRODUCTION: Clinical assessment outweighs the use of investigations in the
      diagnosis of acute appendicitis. Nevertheless, white cell count (WCC) and C
      reactive protein (CRP) are regularly measured in patients with suspected
      appendicitis. The aim of this study was to assess the utility of these markers in
      patients presenting with acute lower abdominal pain. PATIENTS AND METHODS: WCC
      and CRP were measured prospectively in 98 patients presenting with lower
      abdominal pain, and the results were correlated with each patient's outcome.
      RESULTS: No patients with WCC and CRP both in the normal range had acute
      appendicitis. Raised WCC and CRP were poor positive predictors of appendicitis,
      both alone and in combination, and correlated poorly with the development of
      complications. CONCLUSIONS: This result may have important clinical and economic
      implications. We suggest that patients experiencing lower abdominal pain, with
      normal WCC and CRP values, are unlikely to have acute appendicitis and can be
      safely sent home.

PMID- 19102828
TI  - Manipulation under anaesthesia for stiffness following knee arthroplasty.
AB  - INTRODUCTION: Stiffness following knee arthroplasty is a frustrating complication
      and a significantly disabling problem. We present our experience of knee
      stiffness requiring manipulation under anaesthesia (MUA) as the first line of
      treatment following partial or total knee arthroplasty. PATIENTS AND METHODS: All
      stiff knees requiring MUA over a 6-month period from March to August 2007 were
      retrospectively analysed from theatre records and case notes. Data were collected
      regarding demographics, range of knee motion before and after manipulation and at
      subsequent follow-up. Complications of the procedure and outcomes were also
      analysed. RESULTS: Twenty-one patients (11 female, 10 male) underwent MUA. The
      average age was 62 years (range, 56-80 years). Sixteen primary and 3 revision
      total knee replacements underwent manipulation, as did one medial
      unicompartmental replacement and one patellofemoral arthroplasty. General
      anaesthesia with good muscle relaxation was used in all but one patient. The mean
      duration between arthroplasty and MUA was 13.2 weeks (range, 6-32 weeks). The
      range of knee movement improved from a mean range of 10.4-71.2 degrees in the pre
      MUA period to 2.1-94.0 degrees post-MUA and at follow-up was 2.3-91.9 degrees .
      The mean arc of motion improved from 60.2 degrees (range, 40-80 degrees ) pre-MUA
      to 91.9 degrees (range, 45-120 degrees ) post-MUA. The mean improvement in the
      arc of motion was 31.6 degrees (P < 0.001). At an average follow-up of 3 months
      (range, 6 weeks to 8 months), the mean arc of motion was 90.4 degrees (range, 40
      120 degrees ). The mean improvement in knee movement from the pre-MUA at the
      follow-up was 30.2 degrees (P < 0.001). One patient failed to gain any
      improvement from MUA. There were no complications noted from the procedure.
      CONCLUSIONS: MUA has a role in the treatment of early stiffness with excellent
      immediate outcomes. We advocate that MUA should be the first line of management
      for stiff knee arthroplasties after failed physiotherapy.

PMID- 19102829
TI  - [Construction and preliminary panning of Fab phage display antibody library
      against respiratory syncytial virus].
AB  - OBJECTIVE: To construct a human phage display antibody library, which will help
      to develop new drugs and vaccines against respiratory syncytial virus (RSV) and
      solve many of the issues that have limited the progression and application of
      murine monoclonal antibodies (McAbs) in the clinic. This can provide a platform
      for human antibody preparation and diagnosis, prophylaxis and therapy of RSV
      infection in children. METHODS: Peripheral blood lymphocytes were isolated from
      52 children with RSV infection. cDNA was synthesized from the total RNA of
      lymphocytes. The light and heavy chain Fd (VH-CH1) fragments of immunoglobulin
      gene were amplified by RT-PCR. The amplified products were cloned into phagemid
      vector pComb3x and the clone samples were electrotransformed into competent
      E.coli XL1-Blue. The transformed cells were then infected with M13K07 helper
      phage to yield recombinant phage antibody of Fabs. The plasmids extracted from
      amplified E.coli were digested with restriction endonucleases Sac I, Xba I, Spe I
      and Xho I to monitor the insertion of the light or heavy chain Fd genes. RSV
      virions were utilized as antigens to screen Fab antibodies. RESULTS: By
      recombination of light and heavy chain genes, an immune Fab phage display
      antibody library against RSV containing 2.08x10(7) different clones was
      constructed, in which 70% clones had light chains and heavy chain Fd genes. The
      capacity of Fab phage antibody gene library was 1.46x10(7) and the titre of the
      original Fab antibody library was about 1.06x10(12) pfu/mL. The antibody library
      gained an enrichment in different degrees after the preliminary panning.
      CONCLUSIONS: Utilizing the technology of phage display, an immune Fab phage
      display antibody library against RSV was successfully constructed in this study,
      which laid a valuable experimental foundation for further study and created
      favorable conditions for preparing human McAbs. This may also contribute to the
      improvement in the diagnosis, therapy and prophylaxis of RSV infection in
      children.

PMID- 19102830
TI  - [Multicenter investigation for incidence of periventricular leukomalacia in
      premature infants in China].
AB  - OBJECTIVE: Sponsored by the Subspecialty Group of Neonatology of Pediatric
      Society, China Medical Association, more than 10 large-scale hospitals
      participated in the near two-year multicenter investigation for brain injuries in
      premature infants in China. This study presented the investigation result for the
      incidence of periventricular leukomalacia (PVL) in premature infants from 10
      Third Class A Level hospitals. METHODS: The premature infants with a gestation
      age<37 weeks in the 10 hospitals were given routine cranial ultrasound scanning
      within seven days after birth, and then repeated every 3-7 days until discharge
      from January 2005 to August 2006. The severity of PVL was graded based on de
      Vries classification. RESULTS: A total of 4 933 premature infants were enrolled.
      The total incidence of PVL and the incidence of cystic PVL were 2.3% (112/4 933)
      and 0.3% (16/4 933), respectively. Of the 112 PVL cases, 96 (85.7%) were with
      grade I, 14 (12.5%) with grade II, and 2 (1.8%) with grade III. The incidence of
      PVL in 4 maternal and child health care hospitals were significantly lower than
      that in 6 general or children's hospitals (1.4% vs 2.8%) (X2=10.284, P<0.01).
      Vaginal delivery and mechanical ventilation were possible high-risk factors for
      the development of cystic PVL. CONCLUSIONS: The data of the multicenter
      investigation can basically reflect the situation about the occurrence of PVL in
      premature infants in major big cities of China. It is important to improve the
      ability to recognize the sonogram of non-cystic periventricular white matter
      injury.

PMID- 19102831
TI  - [Relationship of the disease severity with ACE gene polymorphism and serum ACE
      activity in preterm infants].
AB  - OBJECTIVE: To investigate the relationship of disease severity with angiotensin
      converting enzyme (ACE) gene insertion/deletion (I/D) polymorphism and serum ACE
      activity in preterm infants during the first 7 days of life. METHODS: ACE
      genotypes were determined in 85 preterm infants admitted to the neonatal
      intensive care unit (NICU). Serum ACE activity was measured and disease severity
      was evaluated by the Neonatal Critical Score (draft) 1, 3 and 7 days after birth.
      RESULTS: Of the 85 preterm infants, DD genotype was found in 19 cases, ID
      genotype in 34 cases and II genotype in 32 cases. On the 1st day of life, serum
      ACE activity in the DD genotype (33.42+/-7.93 U/L) and the ID genotype groups
      (31.53+/-7.56 U/L) were significantly higher than that in the II genotype group
      (25.53+/-7.56 U/L) (P<0.01). After 3 and 7 days of life, serum ACE activity
      decreased in the three groups, but the DD genotype group remained the highest ACE
      activity, followed by the ID genotype and the II genotype groups. On the 1st day
      of life, the critical score of the DD genotype group (87.37+/-8.30) was lower
      than the ID genotype (95.82+/-5.85) and the II genotype groups (95.88+/-6.85)
      (P<0.01). On the 3rd day, the critical score of the DD genotype group was still
      lower than the ID genotype group (92.95+/-7.10 vs 96.94+/-5.85) (P<0.05).
      CONCLUSIONS: ACE gene I/D polymorphism may be associated with the disease
      severity in preterm infants. The DD genotype carriers present more severe disease
      status, with higher serum ACE activity. Although the disease status can influence
      serum ACE activity, serum ACE activity is determined by the ACE genotype.

PMID- 19102832
TI  - [Relationship between brainstem auditory evoked potential and serum neuron
      specific enolase in neonates with asphyxia].
AB  - OBJECTIVE: To study the correlation between brainstem auditory evoked potential
      (BAEP) and serum neuron-specific enolase (NSE) in neonates with asphyxia and
      explore the role of NSE in the evaluation of hearing impairment following
      asphyxia. METHODS: Fifty-two term neonates with asphyxia, including 38 cases of
      simple asphyxia (mild: 23 cases; severe: 15 cases) and 14 cases of asphyxia
      complicated by hypoxic-ischemic encephalopathy (HIE), were enrolled. In the
      double-blind trial, BAEP and NSE were simultaneously detected 7 days after birth.
      The patients who did not pass BAEP test received another BAEP and NSE
      examinations 3 months after birth. Thirty healthy term neonates served as normal
      control group. RESULTS: Of the 52 neonates with asphyxia, 50.0% and 21.2% of
      patients failed the initial and the second BAEP tests, respectively. The
      detection rates of BAEP anomalies in the simple severe asphyxia group in the
      initial and the second tests (63.3% and 26.3%, respectively) were significantly
      higher than those in the simple mild asphyxia group (36.9% and 5.9%,
      respectively)(P<0.05). The neonates with asphyxia complicated by HIE showed a
      higher detection rate of BAEP anomalies in the second test compared with the
      asphyxiated neonates without HIE (31.3% vs 16.7%; P<0.05). Mean serum NSE levels
      in asphyxiated neonates were significantly higher than those in normal controls
      (<0.01). There were significant differences in serum NSE levels between the
      neonates with mild and severe asphyxia (26.70+/-2.34 microg/L vs 17.18+/-3.16
      microg/L; P<0.01). The asphyxiated neonates with HIE had serum NSE levels similar
      to the simple severely asphyxiated neonates. Serum NSE levels in patients who
      failed the initial BAEP test were significantly higher than those who passed the
      test (25.69+/-4.12 microg/L vs 17.15+/-3.09 microg/L; <0.01). Serum NSE levels
      had a positive correlation with wave V reaction threshold detected in the BAFP
      test (<0.05). CONCLUSIONS: The serum level of NSE is closely correlated with
      BAEP, and it may be useful to the evaluation of the hearing impairment and the
      outcome in neonates with asphyxia.

PMID- 19102833
TI  - [Relationship between the growth rate of corpus callosum and neuromotor delay in
      premature infants].
AB  - OBJECTIVE: To study the relationship between the growth rate of the corpus
      callosum and neurological motor development in premature infants. METHODS: Fifty
      infants whose gestational ages were less than 34 weeks and who were admitted to
      the neonatal intensive care unit from March 2007 to August 2007 were enrolled.
      From 0 to 6 weeks of postnatal age, the sagittal midline cranial sonography via
      anterior fontanel was performed, once weekly. The length and the morphology of
      the corpus callosum were measured. The 52-neuromotor examinations were performed
      at 3 months of corrected gestational age. RESULTS: The mean length of the corpus
      callosum was 39.16 mm at birth. The mean growth rate of the corpus callosum
      during the first 6 weeks of life was 1.05 mm/week. Fourteen infants showed
      abnormal neuromotor development and 36 had normal-neuromotor function at 3 months
      of corrected gestational age. A decreased growth rate of the corpus callosum was
      observed in the abnormal nervimotion group between 2 and 3 weeks (0.68 mm/week vs
      1.17 mm/week) and between 4 and 5 weeks (0.86 mm/week vs 1.12 mm/week) after
      birth compared with that in normal nervimotion group (p<0.05). The total growth
      rate of the corpus callosum from 2 to 6 weeks after birth in the abnormal
      nervimotion group was also lower than that in the normal nervimotion group (0.91
      mm/week vs 1.15 mm/week; p<0.01). CONCLUSIONS: A neuromotor delay at 3 months of
      corrected gestational age may be associated with the decreased growth rate of the
      corpus callosum between 2 and 6 weeks of life in premature infants.

PMID- 19102834
TI  - [Risk factors for fungal pneumonia in neonates: analysis of 160 cases].
AB  - OBJECTIVE: To study the risk factors for the development of fungal pneumonia in
      neonates. METHODS: A total of 260 neonates with nosocomial infectious pneumonia
      were classified into two groups: fungal pneumonia (n=160) and bacterial pneumonia
      (n=100). Their medical data were retrospectively studied. RESULTS: Eighty-seven
      percent of patients in the fungal pneumonia group had a duration of hospital stay
      of >10 days, but 30.1% of patients in the bacterial pneumonia group (p<0.01). The
      preterm infants in the fungal pneumonia group accounted for 49.5%, which was
      significantly higher than that in the bacterial pneumonia group (22.0%) (p<0.01).
      In the fungal pneumonia group, 59.9% of patients showed a weight of <2 500 g, but
      34.0% of patients in the bacterial pneumonia group (p<0.01). The duration of the
      combined use of more than two broad-spectrum antibiotics (p<0.05) and the total
      duration of antibiotics use in the fungal pneumonia group was significantly
      longer than that in the bacterial pneumonia group (p<0.05). Nosocomial infectious
      bacterial pneumonia was common as the primary disease of fungal pneumonia
      (n=145). CONCLUSIONS: Premature delivery, lower weight, longer duration of
      hospital stay and antibiotics use, and combined use of more than two broad
      spectrum antibiotics may increase the risk of fungal pneumonia in neonates. The
      development of fungal pneumonia may be related to nosocomial infectious bacterial
      pneumonia in neonates.

PMID- 19102835
TI  - [Effects of mechanical ventilation on plasma IL-6, IL-10 and TNF-alpha in
      children after cardiopulmonary bypass].
AB  - OBJECTIVE: To study the effects of different models of mechanical ventilation on
      inflammatory cytokines, IL-6, IL-10 and TNF-alpha, in children after
      cardiopulmonary bypass (CPB). METHODS: Sixty patients who underwent CPB were
      randomly divided into group A and group B. After CPB, group A was ventilated with
      high tidal volume (VT, 10-12 mL/kg) /low positive end-expiratory pressure (PEEP,
      3-5 cm H2O), while group B was ventilated with low VT (6-8 mL/kg) /high PEEP (6-9
      cm H2O). Plasma levels of IL-6, IL-10 and TNF-alpha were measured before
      operation, at the end of the operation, and 1 and 6 hrs after operation. RESULTS:
      Serum levels of IL-6, IL-10 and TNF-alpha in both groups increased significantly
      at the end of the operation and reached a peak by 1 hr after operation. Group B
      showed lower serum levels of IL-6, IL-10 and TNF-alpha than group A 1 and 6 hrs
      after operation. CONCLUSIONS: Mechanical ventilation with low VT /high PEEP may
      more effectively inhibit the release of inflammatory cytokines than that with
      high VT /low PEEP in children after CPB.

PMID- 19102836
TI  - [Follow-up study on levetiracetam monotherapy in children with epilepsy].
AB  - OBJECTIVE: To evaluate the efficacy and tolerability of levetiracetam (LEV) in
      the treatment of epilepsy as a monotherapy in children. METHODS: Thirty-two
      children with epilepsy (age ranged from 8 months to 12 years) and who had
      received LEV monotherapy were investigated by a self-controlled and open-label
      research. LEV was administered at a dose of 10 mg/kg.d, and increased by 10
      mg/kg.d per week till to the target dose (20-40 mg/kg.d), with a mean dose of 35
      mg/kg.d. RESULTS: Thirty-one patients were followed up for more than three
      months. Twenty-five patients (80.6%) had at least 50% reduction in seizures, 22
      cases (70.9%) became seizure-free, and LEV therapy was discontinued in 5 patients
      (16.1%) due to either an inadequate seizure control or aggravated seizures. The
      therapy-related adverse events included mood and behavioral changes (6/31,
      19.4%), asthenia (2/31, 6.5%), somnolence (2/31, 6.5%), and skin rashes (1/31,
      3.2%). The adverse effects were spontaneously disappeared or disappeared after
      reducing the LEV dose. CONCLUSIONS: LEV monotherapy is effective and safe for the
      control of partial and generalized tonic-clonic seizures in children with
      epilepsy. LEV appears to be a promising anti-epileptic drug for monotherapy in
      children with epilepsy.

PMID- 19102837
TI  - [Relationship between acute pancreatitis and systemic inflammation response
      syndrome in children].
AB  - OBJECTIVE: To study the clinical features of children with acute pancreatitis
      complicated by systemic inflammatory response syndrome (SIRS). METHODS: Clinical
      data of 71 children with acute pancreatitis from May 2005 to June 2007 were
      retrospectively studied. According to complications with or without SIRS, the
      patients were classified into two groups: SIRS (n=30) and non-SIRS (n=41). The
      SIRS group was subdivided into three groups based on the item number consistent
      with SIRS diagnostic criteria: S1 (2 items), S2 (3 items) and S3 (4 items).
      RESULTS: More patients had severe abdominal pain (n: 12 vs 3) and fever (n: 25 vs
      15) in the SIRS group than in the non-SIRS group (p<0.01). The serum C-reactive
      protein (CRP) levels (49.61+/-8.09 mg/L) in the SIRS group were significantly
      higher than those in the non-SIRS group (7.98+/-2.82 mg/L) (p<0.01). The serum
      calcium level (1.93 mol/L) in the SIRS group was statistically lower than that in
      the non-SIRS group (2.81 mol/L)(p<0.01). Among the SIRS group, the S3 group
      showed the highest CRP level (120.40+/-10.04 mg/L), followed by the S2 group
      (75.78+/-9.50 mg/L) and S1 group (28.51+/-8.51 mg/L) (p<0.01). The highest
      sensitivity (50%) and negative predictive value (96.8%) for the diagnosis of
      severe acute pancreatitis was obtained for a CRP cut-off at 110 mg/L. The imaging
      changes were more severe in the SIRS group than in the non-SIRS group.
      CONCLUSIONS: Severe abdominal pain and fever were common clinical symptoms in
      children with acute pancreatitis complicated by SIRS. Serum CRP and calcium
      levels as well as imaging changes are important markers for the severity
      evaluation of acute pancreatitis. The patients with serum CRP level above 110
      mg/L or with more than three items consistent with SIRS diagnostic criteria are
      at high risk for the development of severe acute pancreatitis.

PMID- 19102838
TI  - [Clinical characteristics and therapy of severe Mycoplasma pneumonia in
      children].
AB  - OBJECTIVE: To study the clinical characteristics, therapeutic regimen and outcome
      of severe Mycoplasma pneumonia (MP) in children. METHODS: Clinical data of 79
      children with MP, including 69 mild and 10 severe cases, were retrospectively
      analyzed. The 10 children with severe MP were followed-up. RESULTS: In severe MP
      cases, the fever duration prior to hospitalization and the total fever duration
      were more prolonged, peripheral blood leucocytes counts, C-reactive protein and
      erythrocyte sedimentation rate increased, and serum IgM and IgE levels increased
      as compared to mild MP cases. Of the 10 cases of severe MP, 4 manifested as
      pulmonary consolidation, 4 as pulmonary consolidation complicated by moderate to
      large pleural effusion and 2 as progressively worsening pulmonary radiographic
      findings. Nine severe MP cases were administered with glucocorticoid as well as
      antibiotics, and the therapeutic effect was satisfactory. In the convalescence
      stage, bronchofiberoscope lavages were used in 5 severe cases because of
      persistent pulmonary consolidation. CONCLUSIONS: Severe MP was characterized by
      rapid progression, pulmonary consolidation, moderate to severe pleural effusion,
      obviously increased inflammatory indexes, and poor therapeutic reaction to simple
      macrolide antibiotics. Besides antibiotics, glucocorticoid should be used for
      severe MP cases as soon as possible. For severe cases with persistent pulmonary
      consolidation, bronchofiberoscope lavages are recommended.

PMID- 19102839
TI  - [Effect of endemic fluorosis on children's intelligence development: a Meta
      analysis].
AB  - OBJECTIVE: To investigate the effect of high levels of fluoride on children's
      intelligence development by analyzing the literatures systematically. METHODS:
      The literatures on the relationship between endemic fluorosis and children's
      intelligence development published between 1995 and 2007 were retrieved
      electronically and manually. A total of 13 relevant literatures that met the
      inclusion criteria were included for Meta analysis. Meta analysis was performed
      using the Coorporative network software RevMan 4.3. RESULTS: The subjects of the
      13 literatures included 2 508 children from the high fluoride group and 2 330
      children from the control group. Meta analysis showed these literatures were
      inhomogenous (x2=268.05, p<0.01). Therefore a random effect model was used. The
      average effect scale (OR=-7.14; 95%CI: -9.90, -4.37) suggested a negative
      correlation between high fluorosis exposure and children's intelligence
      development. CONCLUSIONS: Exposure to high levels of fluoride may adversely
      influence children's intelligence development.

PMID- 19102840
TI  - [Electroencephalographic biofeedback for the treatment of attention deficit
      hyperactivity disorder in children].
AB  - OBJECTIVE: Attention deficit hyperactivity disorder (ADHD) is a common behavioral
      disorder in children. When the children fulfill cognition tasks, brain theta wave
      activity increases and beta wave activity weakens. This study aimed to explore
      the efficacy of electroencephalographic (EEG) biofeedback therapy for ADHD in
      children by assessing the changes of the ratio of brain theta to beta waves and
      the integrated visual and auditory continuous performance test (IVA-CPT).
      METHODS: EEG biofeedback therapy was performed in 30 children with ADHD. The
      ratio of brain theta to beta waves was measured before and after therapy. IVA-CPT
      was used to assess the effectiveness of biofeedback therapy. RESULTS: After two
      courses of treatment, the mean ratio of brain theta to beta waves in the 30
      children with ADHD was significantly reduced from 12.32+/-4.35 (before treatment)
      to 6.54+/-1.27 (p<0.01). IVA-CPT demonstrated that the values of six indexes
      measured, including integrate reaction control quotient, integrate attention
      quotient, auditory and visual reaction control quotients, auditory and visual
      attention control quotients, were significantly increased after biofeedback
      therapy (p<0.01). CONCLUSIONS: EEG biofeedback can reduce the ratio of brain
      theta to beta waves and lead to significant decreases in inattention and
      hyperactivity and it is effective for treatment of ADHD in children.

PMID- 19102841
TI  - [A case-control study on life style and health status for mothers of preterm
      infants].
AB  - OBJECTIVE: This study investigated the life style and health status of preterm
      and term infants' mothers in order to explore the risk factors for preterm
      delivery. METHODS: A total of 600 matched cases, including 120 pairs of preterm
      infants and their mothers and 180 pairs of term infants and their mothers were
      recruited. All of the mothers participated in a questionnaire survey on life
      style and health status during or before pregnancy. General data of the infants
      were also collected. Logistics regression analysis was used for evaluating the
      risk factors for preterm delivery. RESULTS: The height, body weights and body
      mass index before pregnancy in preterm infants' mothers were significantly lower
      than those in term infants' mothers (p<0.05). The birth height and weights and
      Apgar scores in preterm infants were significantly lower than those in term
      infants (p<0.05). The whole nutritional Knowledge-Attitude-Practice (KAP) scores
      in preterm infants' mothers were significantly lower than those in term infants'
      mothers (P<0.05). Multiple factor regression analysis showed that recurrent
      abortions before gestation (OR=2.332, P<0.05) and premature rupture of membrane
      before delivery (OR=7.979, P<0.01) were risk factors for preterm delivery, while
      maternal nutritional KAP scores (OR=0.949, P<0.01) and body weights before
      pregnancy (OR=0.954, P<0.05) were protective factors. CONCLUSIONS: The women with
      low body weight, low nutritional KAP scores or recurrent abortions history before
      pregnancy or presenting premature rupture of membrane before delivery are at high
      risk for preterm delivery.

PMID- 19102842
TI  - [Establishment of quantifying and typing analysis of 16S rRNA gene by real-time
      PCR].
AB  - OBJECTIVE: To explore a new method of rapid and reliable diagnosis of bacterial
      infectious diseases such as purulent meningitis and septicemia. METHODS: A pair
      of universal primers and a set of probes (including universal fluorescence probe,
      Gram-positive probe and Gram-negative probe) were designed based on the bacterial
      highly conserved region of 16S rRNA gene. By using the FQ-PCR method, 12 standard
      strains, 23 clinical cultural isolations and the controls such as HBV,
      Cryptococcus histolyticus, Blastomyces albicans and human DNA were detected with
      the three kinds of probes. The correlation among the results of the three kinds
      of probes detection was analyzed. RESULTS: The determination of 16S rRNA gene
      with FQ-PCR was a highly specific and sensitive method and not cross-reactive
      with human DNA, virus or fungi. The least amount of 10 copies of 16S rRNA gene
      which corresponded to 2 bacteria could be detected with FQ-PCR. Twelve standard
      strains and 23 clinical cultural isolations were detected by FQ-PCR with the
      three kinds of probes mentioned above. All samples presented positive results
      using the universal probe. The results of 16S rRNA gene detected by the
      Gramjpositive probe were positive to the 18 G+ strains. The results of 16S rRNA
      gene detected by the Gram-probe were positive to the 17 G- strains. CONCLUSIONS:
      The FQ-PCR technique was established for bacteria quantifying and typing using
      the universal primer and the double type probes. This method was convenient and
      rapid in detecting, quantifying and typing bacteria, with a high specificity and
      sensitivity.

PMID- 19102843
TI  - [Adenovirus-mediated VEGF165 gene transfer has neuroprotective effects in
      neonatal rats following hypoxic-ischemic brain damage].
AB  - OBJECTIVE: To investigate the protective effects of adenovirus-mediated vascular
      endothelial growth factor (Ad-VEGF)165 gene transfer against hypoxic-ischemic
      brain damage (HIBD) in neonatal rats. METHODS: Ad-VEGF recombinant adenovirus was
      constructed by bacterial homologous recombination technology. Seven-day-old
      Sprague-Dawley rats were randomly assigned to 4 groups: sham-operated (n=20),
      HIBD (n=25), buffer-treated (n=20), and Ad-VEGF-treated (n=25). The HIBD model
      was prepared by permanent occlusion of left common carotid artery, followed by
      exposure to 8% oxygen for 2 hrs. In the Ad-VEGF-treated and the Buffer-treated
      groups, 2 microL recombinant adenovirus suspension or buffer was injected into
      the left sensorimotor cortex of the rat brain 3 days after HIBD. Seven days after
      transplantation, VEGF165 mRNA expression was detected using RT-PCR. Neuronal
      apoptosis was detected by the terminal deoxynucleotidyl transferase-mediated
      biotinylated deoxyuridine triphosphate nickel end labeling (TUNEL). CD34 and VEGF
      protein were detected using immunohistochemistry. Microvascular density in the
      cerebral cortex was measured based on CD34 positive cells. A radial arm maze test
      was performed from 30 postnatal days to evaluate long-term learning and memory
      functions. At 35 postnatal days, the rats were sacrificed for cerebral
      histological examinations by hematoxylin and eosin. RESULTS: The expression of
      VEGF165 mRNA increased in the Ad-VEGF-treated group more than in the untreated
      HIBD and the buffer-treated groups (p<0.05). The number of apoptotic neurons was
      less in the Ad-VEGF-treated group compared with that in the untreated HIBD and
      the buffer-treated groups (p<0.05). Microvascular density and VEGF positive cells
      increased in the Ad-VEGF-treated group compared with that in the untreated HIBD
      and the buffer-treated groups (p<0.05). In the radial arm maze test, the Ad-VEGF
      treated group had more improved achievements than the HIBD and the buffer groups
      (p<0.05). Neuronal degeneration and necrosis were lessened in the Ad-VEGF-treated
      group compared with the HIBD and the buffer groups. CONCLUSIONS: Ad-VEGF gene
      transfer can increase the expression of VEGF mRNA and VEGF protein, decrease
      neuronal apoptosis, and increase angiopoiesis in the brain. This attenuates brain
      damage and improves long-term learning and memory functions in neonatal rats
      after HIBD.

PMID- 19102844
TI  - [Benign infantile convulsions associated with rotavirus gastroenteritis: clinical
      analysis of 18 cases].

PMID- 19102845
TI  - [Follow-up of auditory function in children with early congenital syphilis].

PMID- 19102846
TI  - [Clinical analysis of 65 cases of infantile tinea versicolor].

PMID- 19102847
TI  - [Drug resistance of pathogens in infants with community acquired pneumonia from
      the south suburb of Xi'an].

PMID- 19102849
TI  - [Misdiagnosis of 9 cases of congenital dermal sinus].

PMID- 19102848
TI  - [Acute intestinal pseudo-obstruction secondary to acute diarrhea in 10 children].

PMID- 19102850
TI  - [Nodular panniculitis in a neonate].

PMID- 19102851
TI  - [A case report of Silver-Russell syndrome].

PMID- 19102852
TI  - [Research advance on pediatric antipyretic].

PMID- 19102853
TI  - [2008 Task force guidelines for amiodarone use in the treatment of arrhythmias
      (no abstract)].

PMID- 19102854
TI  - [Summary of the tenth national congress of cardiology of Chinese medical
      association (no abstract)].

PMID- 19102857
TI  - [Predictive value for long term cardiac events by admission B-type natriuretic
      peptide and pulmonary capillary wedge pressure in patients with chronic heart
      failure].
AB  - OBJECTIVE: To evaluate the predictive value of admission plasma B-type
      natriuretic peptide (BNP) and pulmonary capillary wedge pressure (PCWP) for long
      term cardiovascular events in patients with chronic heart failure (CHF). METHODS:
      A total of 134 patients [70 males and 64 females, mean age (71.28 +/- 8.22)
      years] with CHF were included in this study. PCWP was measured with a Swan-Ganz
      catheterization and plasma BNP level was determined by a rapid immunofluorescence
      assay (Triage, Biosite, USA) in all patients on admission day. Left ventricular
      end diastolic diameter (LVEDD) and cardiothoracic ratio (CRT) were measured
      within 24 hours before or after catheterization. All CHF patients received
      conventional therapy and the rates of cardiac death and rehospitalization were
      used as end points during 3-year follow up. RESULTS: (1) LVEDD, CRT, PCWP and BNP
      were increased in patients with cardiac events compared with patients without
      cardiac events (P < 0.01). (2) Multivariant logistic analysis showed that PCWP
      (OR = 1.423, 95% CI 1.163 - 1.741) and BNP (OR = 1.005, 95% CI 1.002 - 1.007)
      were the independent factors for cardiac events. (3) The area under the receiver
      operating curve (ROC) of BNP and PCWP to predict cardiac death was 0.846 (95% CI
      0.771 - 0.922) and 0.762 (95% CI 0.666 - 0.875), respectively. The sensitivity
      was 76.5% and the specificity was 75.2% with BNP cutoff point of 720.5 ng/L, and
      the sensitivity was 68.1% and the specificity was 76.2% with PCWP cutoff point of
      19.5 mm Hg (1 mm Hg = 0.133 kPa) for predicting cardiac deaths. (4) The survival
      rate of patients with BNP < or = 702.5 ng/L and PCWP < or = 19.5 mm Hg were
      significantly higher than that in patients with BNP > 702.5 ng/L (OR = 4.383, 95%
      CI 1.407 - 13.650) and PCWP > 19.5 mm Hg (OR = 2.843, 95% CI 1.013 - 8.854).
      CONCLUSION: Both plasma BNP and PCWP on admission day are independent predictors
      for long term cardiac events in patients with CHF.

PMID- 19102858
TI  - [Effects of valsartan on sarcoplasmic reticulum calcium adenosine triphosphatase,
      protein kinase A and protein phosphatase 1 alpha in a rabbit model of heart
      failure].
AB  - OBJECTIVE: To investigate the effects of valsartan on expressions of myocardial
      sarcoplasmic reticulum calcium adenosine triphosphatase (SERCA2), protein kinase
      A (PKA) and protein phosphatase 1 alpha (PP1alpha) in a rabbit model of heart
      failure. METHODS: Rabbits were divided into sham-operated group, heart failure
      group (volume overload by aortic valve destruction induced aortic insufficiency
      plus pressure overload induced by abdominal aortic banding) and heart failure
      plus valsartan (20 mgxkg(-1)xd(-1), n = 6 each). Seven weeks later,
      echocardiography examination was performed and SERCA2, PKA, PP1alpha protein and
      mRNA expressions were detected by Western blot and RT-PCR. RESULTS: Compared with
      the with sham operated rabbits, LVMI and LVEDP in heart failure rabbits were
      significantly increased while left ventricular shorten fraction (LVFS) and
      ejection fraction (EF) were significantly decreased (all P < 0.05), these changes
      could be significantly attenuated by valsartan treatment (all P < 0.05). SERCA2,
      PKA expressions at protein and mRNA levels were significantly downregulated and
      PP1alpha expressions significantly upregulated in heart failure rabbits than sham
      operated rabbits (all P < 0.05) and these changes could be significantly
      attenuated by valsartan (all P < 0.05). CONCLUSION: Valsartan improved cardiac
      function in volume and pressure overload induced heart failure rabbits possibly
      by upregulating expressions of myocardial SERCA2, PKA and downregulating
      expression of myocardial PP1alpha.

PMID- 19102861
TI  - [Incidence, risk factors and management of pericardial effusion post
      radiofrequency catheter ablation in patients with atrial fibrillations].
AB  - OBJECTIVE: Pericardial effusion (PE) is a major complication of atrial
      fibrillation ablation (AFB). We analyzed the incidence, risk factors and
      managements of PE post AFB (radiofrequency catheter ablation). METHODS: A total
      of 156 consecutive patients with AF [male 108, paroxysmal AF 114, (57.6 +/- 11.3)
      years], who underwent AFB guided by a three-dimensional mapping system (CARTO or
      CARTO-Merge, Biosense-Webster Inc., Diamond Bar, California) and a circular
      mapping catheter (Lasso, Biosense-Webster Inc., Diamond Bar, California), were
      included in this study. The ablation strategy included circumferential pulmonary
      veins isolation (CPVI), linear ablation and/or complex fractionated atrial
      electrograms (CFAEs) ablation. Electrophysiological data and vital signs of
      patients were recorded by a multiple physiological recorder (Prucka, GE Medical
      Systems) during ablation. Ablation process, sites, duration and other related
      factors were also recorded. Echocardiography and other examinations were
      performed for diagnosing and monitoring PE. RESULTS: CPVI were achieved in all
      156 patients. Incidence of PE was 10.3% (16/156) post AFB. One patient developed
      acute cardiac tamponade and emergency drainage of the pericardial effusion was
      performed through a median sternotomy and patient recovered without complications
      during the 18 months follow-up. The rest 15 PE patients with small PE received
      outpatient care and no invasive treatment was needed and PE disappeared after 3
      months in 6 patients and after 6 months in 9 patients. Univariate analysis showed
      that the composition of gender (P < 0.01), ablation in coronary sinus (CS, P =
      0.026), ablation of CFAEs (P = 0.037) and superior vena cava (SVC, P = 0.041)
      were risk factors for PE. Logistic regression analysis showed that female gender
      [beta = 3.594, exp (b) = 36.4, 95% confidence interval (CI): 4.2 - 312.1, P =
      0.001] and ablation in CS [beta = 2.419, exp (b) = 11.2, 95% CI: 1.0 - 124.6, P =
      0.049] were independent risk factors for PE post AFB. CONCLUSIONS: PE is a common
      complication of AFB, female gender and ablation in CS were independent risk
      factors for PE. Most PE patients experienced spontaneous recovery but emergency
      treatment was needed for patient with cardiac tamponade.

PMID- 19102859
TI  - [Therapeutic effects of recombinant human growth hormone and mesenchymal stem
      cells transplantation alone or in combination in adriamycin induced
      cardiomyopathy rat model].
AB  - OBJECTIVE: To investigate the therapeutic effects of recombinant human growth
      hormone (rhGH) and mesenchymal stem cells (MSCs) transplantation alone or in
      combination in adriamycin-induced cardiomyopathy (CM) rat model. METHODS: Wistar
      rats were divided into normal (n = 6), CM (n = 9), rhGH (2 mg/kg, subcutaneous
      injection, qod for 1 month, n = 6), MSCs transplantation (MSCs group, 5 x
      10(6)/100 microl, n = 7) and rhGH + MSCs (G + M group, n = 7) groups. After 1
      month, hemodynamic data, the ratio of heart weight/body weight (HW/BW) and left
      ventricular weight/body weight (LW/BW) were obtained. The myocardial MSCs marked
      by BrdU were detected by immunohistochemistry. Cardiac myosin heavy-chain (MHC)
      and its isozymes were detected by SDS-PAGE technique. Serum growth hormone (GH)
      and B-type natriuretic peptide (BNP) levels were measured. RESULTS: Compared to
      CM group, cardiac function remained unchanged in MSC group while significantly
      improved in rhGH group and further improved in G + M group. HW/BW and LW/BW were
      similar among groups (all P > 0.05). The MSCs number in the myocardium of G + M
      group was significantly higher than those of MSCs group. Compared to CM group, V3
      MHC was significantly increased in MSCs group (10.33 +/- 0.33 vs 7.43 +/- 2.08, P
      < 0.05), V1 and V3-MHC were significantly increased in G + M group (86.22 +/-
      1.73 vs 77.47 +/- 2.02, 12.44 +/- 0.31 vs 7.43 +/- 2.08, all P < 0.05). GH levels
      were significantly higher in rhGH and G + M treated animals than that in CM
      animals [(2.50 +/- 0.68) vs (1.37 +/- 0.09) microg/L, (2.48 +/- 0.90) vs (1.25 +/
      0.42) microg/L, all P < 0.05], BNP levels were significantly lower in rhGH, MSCs
      and G + M treated groups than that in CM group [(1270.72 +/- 203.72) vs (1462.44
      +/- 242.87) ng/L, (1385.00 +/- 250.13) vs ( 1475.29 +/- 281.33) ng/L, (1219.31 +/
      126.71) vs (1451.78 +/- 180.93) ng/L, all P < 0.05]. CONCLUSIONS: rhGH but not
      MSC could improve the cardiac function in adriamycin-induced CM rats. Combined
      rhGH and MSCs transplantation therapy could further improve cardiac function
      possibly due to enhanced MSCs growth and transformation into cardiomyocytes.

PMID- 19102862
TI  - [Impact of statins on clopidogrel platelet inhibition in patients with acute
      coronary syndrome or stable angina].
AB  - OBJECTIVE: This prospective registered study was conducted to investigate the
      impact of statins (pravastatin, fluvastatin, atorvastatin) on clopidogrel
      platelet inhibition in patients with acute coronary syndrome (ACS) or stable
      angina. METHODS: A total of 1015 consecutive patients with ACS or stable angina
      underwent coronary angiography/percutaneous coronary intervention (PCI) were
      allocated to pravastatin group (n = 228), fluvastatin group (n = 179),
      atorvastatin group (n = 481) or placebo control group (n = 127). Baseline
      characteristics, coronary angiography/PCI features and acute stent thrombosis,
      platelet aggregation induced by 2, 5, 10 and 20 micromol adenosine diphosphate
      (ADP) at 1 minute (ADP-1), 5 minutes (ADP-5) and maximal platelet aggregation
      (ADP-M) were compared among groups. RESULTS: Baseline and procedural
      characteristics were comparable among the four groups. Acute stent thrombosis
      (pravastatin group 0.9%, fluvastatin group 1.1%, atorvastatin group 1.0% and
      control group 0.8%, all P > 0.05), ADP-1, ADP-5, and ADP-M (all P > 0.05) were
      also similar among groups. Multivariate liner and ordinal logistic analysis
      revealed that age (B = 0.21, P = 0.001), dose of clopidogrel (B = 7.30, P =
      0.002) and use of low-molecular heparin (OR = 6.71, P = 0.01) were independent
      factors for platelet aggregation inhibition efficacy by clopidogrel. CONCLUSION:
      Inhibition of platelet aggregation with clopidogrel was influenced by age,
      clopidogrel dose and low-molecular heparin but not by various statin treatments.

PMID- 19102863
TI  - [Clinical and pathological characteristics of constrictive pericarditis in
      China].
AB  - OBJECTIVE: To summarize the clinical and pathological characteristics of
      constrictive pericarditis in China. METHOD: Data from 150 patients with
      constrictive pericarditis who admitted to our hospital from 2000 to 2007 were
      retrospectively analyzed. RESULTS: Constriction pericarditis was detected by
      echocardiography in 149 out of 150 patients. Pericardial effusion was evidenced
      in 59.3% patients (89/150). The diagnostic accuracy rate for identifying
      constrictive pericarditis by echocardiography (98.7%, 107/109) was comparable to
      that of surgical diagnosis (100%, 109/109). Tuberculosis was the main cause of
      constrictive pericarditis in this cohort (78.7%, 118/150) including 25 (16.7%)
      cases with pathological or etiological evidences of tubercular pericarditis, 8
      (5.3%) cases with pathologically active tuberculous focus elsewhere in the body,
      66 (44.0%) cases with typical clinical tuberculosis manifestation and responded
      to anti-tubercular therapy and 19 (12.7%) cases with a diagnosis of suspicious
      tuberculosis. Pericardiectomy was performed in 108 cases and pericardial biopsy
      and surgical drainage was performed in 1 patient. In hospital death rate was 8.7%
      (13/150, 4 tubercular patients and 9 non-tubercular). CONCLUSION: Tuberculosis is
      the leading cause of constrictive pericarditis in this cohort and the best
      diagnosis tool is echocardiography other than pathological and etiological
      findings in pericardium.

PMID- 19102864
TI  - [Successful treatment of infectious endocarditis with linezolid: a case report
      (no abstract)].

PMID- 19102865
TI  - [Diagnostic value of myocardial perfusion imaging and multislice spiral computed
      tomography for coronary artery disease].
AB  - OBJECTIVE: To investigate the diagnostic value of myocardial perfusion imaging
      (MPI) and multislice spiral computed tomography (MSCT) for coronary artery
      disease (CAD). METHODS: Coronary angiography (CAG), MPI and MSCT were performed
      in 43 patients (36 with suspected, 7 with known CAD). MPI examinations were
      evaluated semiquantitatively by agreement of two experienced observers. SDS
      (summed difference score) > 1 was defined as reversible ischemia, and each
      myocardial segment was allocated to the territory of one of the coronary
      arteries. The MSCT results were defined as positive when stenoses (> or = 50%)
      were found in one main vessel or its main branch vessel. CAG results served as
      "gold standard". The diagnostic values of MPI and MSCT for CAD were compared
      respectively on patient basis and on vessel basis. RESULTS: On patient basis, the
      sensitivity, specificity and accuracy of MPI for diagnosing CAD were 79.17%,
      84.21% and 81.40% which were similar as those of MSCT: 83.33%, 89.47% and 86.05%
      (all P > 0.05). On vessel basis, the sensitivity, specificity and accuracy of MPI
      were 53.19%, 89.02% and 75.97% which were also similar to those of MSCT: 70.21%,
      95.12% and 86.05% (all P > 0.05). CONCLUSION: The non-invasive MPI and MSCT
      provide satisfactory and similar diagnostic information on diagnosing CAD.

PMID- 19102866
TI  - [The value of diagnosis of the harmonic imaging ultrasonic integrated backscatter
      on the very early stage of acute myocardial infarction].
AB  - OBJECTIVE: To study change and the value of diagnosis of harmonic imaging
      ultrasonic integrated backscatter (IBS) on the very early diagnosis of acute
      myocardial infarction (AMI). METHOD: 72 patients were divided 2 groups, A group
      30 cases with AMI at the very early stage of acute myocardial infarction (in 2
      hours), B group 42 cases with typical acute myocardial infarction (in 2 - 12
      hours) were examined by IBS and the cyclic variation of integrated backscatter
      (CVIB) with HP-5500 ultrasonic system in the segment of myocardial infarction and
      no myocardial infarction. RESULTS: In A group the IBS of the segment of AMI are
      very higher than that of the segment of no AMI [(18.8 +/- 3.4) dB vs (8.3 +/-
      1.2) dB, P < 0.01], the CVIB are lower [(6.3 +/- 0.7) dB vs (7.6 +/- 1.1) dB, P <
      0.01]. But in the meanwhile there are no obvious changes in ECG. In B group the
      IBS of the segment of AMI is obvious higher than the normal person and no
      infarction segment in the same heart [(22.2 +/- 4.1) dB vs (8.3 +/- 1.2) dB,
      (21.1 +/- 3.2) dB vs (8.7 +/- 0.9) dB, P < 0.05], but CVIB is obvious lower than
      the normal person and no infarction segment in the same heart [(5.6 +/- 0.8) dB
      vs (7.6 +/- 1.1) dB, P < 0.05; (5.8 +/- 0.7) dB vs (9.3 +/- 0.9) dB, P < 0.01],
      the changes of the ultrasonic is coincidence with ECG. The change of IBS are very
      obvious just as in ECG. CONCLUSION: The result demonstrate that ultrasonic tissue
      characterization with harmonic imaging integrated backscatter can be used for
      diagnosis the very early stage of AMI, and can judge the segment range of AMI and
      function of the whole heart.

PMID- 19102870
TI  - [The role of coronary sinus musculature on electrical conduction between left
      atrium and right atrium in isolated canine heart].
AB  - OBJECTIVE: To investigate electrophysiological characteristics of the coronary
      sinus musculature and explore its role on electrical conduction between left
      atrium and right atrium in isolated canine heart. METHOD: The electrical
      connections between coronary sinus, left atrium and right atrium were detected by
      programmed stimulation delivered at coronary sinus ostium, distal coronary sinus
      and lateral wall of left atrium in a Langendorff model of canine. RESULTS: During
      stimulation delivered at coronary sinus ostium and distal coronary sinus,
      posterior wall of left atrium was firstly activated by electronic signal through
      coronary sinus musculature, the conduct time of coronary sinus ostium stimulation
      and distal coronary sinus stimulation were (44 +/- 21) ms and (41 +/- 15) ms,
      respectively. During stimulation delivered at lateral wall of left atrium,
      electronic signal was firstly observed in coronary sinus. During premature
      stimulation, conduction blockade of coronary sinus to left atrium was evidenced
      in parts of hearts, but electronic conduction of left atrium to right atrium
      remained stable. The ERP at the different stimulation sites of coronary sinus
      ostium and distal coronary sinus, posterior wall of left atrium were (122 +/- 19)
      ms, (114 +/- 12) ms (n = 3) and (107 +/- 17) ms (all P > 0.05). CONCLUSION: A
      conduction way connecting left and right atria exists in coronary sinus which
      might play an important role on inducing and maintaining atrial arrhythmias under
      certain pathological conditions.

PMID- 19102867
TI  - [Factors associated plasma B type natriuretic peptide and N-terminal pro-B-type
      natriuretic peptide levels].
AB  - OBJECTIVE: To identify factors closely associated with plasma B type natriuretic
      peptide (BNP) and N-terminal pro-B-type natriuretic peptide (NT-proBNP) levels.
      METHODS: A total of 1983 people (mean 66 years-old and 694 male) underwent annual
      health check-up in 2006 in Okuizumo district were included in this study. Blood
      pressure, electrocardiogram, conventional blood examination, plasma BNP and NT
      proBNP were measured. RESULTS: BNP is positively correlated with NT-proBNP (r =
      0.89, P < 0.01). Multiple regression analysis showed that age, Hb, pulse rate,
      SBP, TC, gender, TG and creatinine were significantly related to BNP and age,
      creatinine, Hb, gender, TG, TC, SBP, pulse rate were significantly related to NT
      proBNP. NT-proBNP was more easily affected by renal function changes and BNP was
      more easily affected by autonomic nervous system changes. Both BNP and NT-proBNP
      significantly increased in proportion to SBP and age. NT-proBNP and BNP were
      significantly higher in females compared with males (all P < 0.05). NT-proBNP and
      BNP were also negatively correlated with abdominal circumference (all P < 0.05).
      CONCLUSION: In this study population, NT-proBNP and BNP were closely associated
      with age, blood pressure, creatinine, pulse rate, lipid levels, gender and
      abdominal circumferences.

PMID- 19102872
TI  - [The efficacy of tetramethylpyrazine-eluting stents on inhibiting neointima
      formation in porcine coronary arteries].
AB  - OBJECTIVE: The aim of this study was to investigate the mechanism and efficacy of
      tetramethylpyrazine-eluting stents (TES) on inhibiting neointima formation in
      porcine coronary arteries. METHODS: TES was prepared by tetramethylpyrazine spray
      coated in bare metal stents (BMS). Pigs were implanted with TES or BMS (n = 7
      each), respectively. Quantitative coronary angiography (QCA) and intravascular
      ultrasound (IVUS) were performed before, immediately after stenting and at 28
      days after stenting. Coronary arteries segments (5 cm) before and post stenting
      area (5 cm) as well as at stenting location were harvested at 28 days post
      stenting for histopathological examinations (inflammation, vascular smooth muscle
      cells proliferation and apoptosis). RESULTS: Follow up QCA at 28 days showed that
      percentage diameter stenosis were significantly lower in the TES group than that
      in the BMS group [(10.0 +/- 2.1)% vs (60.2 +/- 23.5)%, P = 0.01]. The lumen area
      determined by IVUS was similar between the two groups and there was no in-stent
      thrombosis in TES or BMS treated animals. Internal elastic lamina area was
      significantly larger while the neointimal area [(1.51 +/- 0.45) mm(2) vs (4.60 +/
      1.39) mm(2), P = 0.04] was significantly smaller in the TES group than that in
      the BMS group. Histopathological assessments showed fewer inflammatory cells in
      the stented-coronary artery walls than those at the border zones of stenting in
      both groups. The number of proliferating cells were significantly decreased while
      apoptotic cells were significantly increased in the TES group compared with the
      BMS group (all P < 0.05). CONCLUSION: TES could effectively reduce in-stent
      restenosis in this porcine model by attenuating vascular smooth muscle
      proliferation and enhancing vascular smooth muscle apoptosis post stenting.

PMID- 19102871
TI  - [Effects of telmisartan on endoplasmic reticulum stress induced cardiomyocyte
      apoptosis in abdominal aortic banded rats].
AB  - OBJECTIVE: To investigate the effects of telmisartan on endoplasm reticulum (ER)
      stress signal pathways and cardiomyocyte apoptosis in abdominal aortic banded
      rats. METHODS: Male SD rats were randomly divided into sham-operated group,
      abdominal aortic banding group (AAB) and AAB + telmisartan (5 mgxkg(-1)xd(-1) per
      gavage, beginning at 1 week before AAB for 8 weeks, n = 10 each). Ten weeks post
      AAB, hemodynamic measurements were performed, whole heart and left ventricular
      weights were obtained, cardiomyocyte apoptosis was measured by TUNEL method.
      Myocardial GRP78 and CHOP protein expressions were detected by Western blot and
      immunohistochemistry. RESULTS: The ratio of left ventricular weight to body
      weight, the ratio of heart weight to body weight, left ventricular end diastolic
      pressure and the apoptosis index were significantly increased while left
      ventricular end systolic pressure and +/- dp/dt(max) were significantly decreased
      in AAB group than those in sham-operated group (all P < 0.01), these changes
      could be significantly attenuated by telmisartan (all P < 0.01). Moreover,
      myocardial GRP78 and CHOP expressions were significantly upregulated in AAB group
      than those in sham-operated group and telmisartan could significantly
      downregulate the increased GRP78, CHOP expressions (all P < 0.01). CONCLUSIONS:
      Increased ER stress might be responsible for enhanced cardiomyocyte apoptosis in
      AAB rats. Telmisartan effectively attenuated the cardiomyocyte apoptosis and
      cardiac hypertrophy in AAB rats possibly through reducing ER stress.

PMID- 19102873
TI  - [Fenofibrate improves energy metabolism and attenuates isoproterenol induced
      acute myocardial ischemic injury in rats via PPAR alpha activation].
AB  - OBJECTIVE: To observe the effects of peroxisome proliferator-activated receptor
      (PPAR) alpha agonist Fenofibrate (FF) on energy metabolism and histology in
      isoproterenol (Iso) induced acute myocardial ischemic injury model. METHODS: Male
      Wistar rats were randomly divided into control group, Iso group (5 mg/kg, i.p.)
      and FF group (80 mgxkg(-1)xd(-1) per gavage for 7 days, then Iso 5 mg/kg, i.p. n
      = 30 each). Twenty-four hours post Iso, heart weight/body weight ratio,
      myocardial histopathological changes (HE staining), serum and myocardial free
      fatty acids (FFA) levels, the myocardial protein expression of PPARalpha (Western
      blot) were determined. RESULT: Compared with the control group, pathological
      myocardial injuries were observed under light microscope in Iso treated hearts
      and FF pretreatment could significantly attenuate these changes [necrotic area: 0
      vs (10.00 +/- 3.00)% vs (7.36 +/- 2.60)%], the heart weight/body weight ratio,
      FFA in serum (501.17 +/- 43.69 vs 939.53 +/- 69.51 vs 736.53 +/- 70.30
      micromol/L) and myocardium (62.01 +/- 9.19 vs 140.59 +/- 19.34 vs 116.28 +/-
      14.03 micromol/L) were significantly increased while myocardial protein
      expressions of PPARalpha (251.57 +/- 10.95 vs 191.97 +/- 10.74 vs 215.08 +/-
      9.61) was significantly downregulated in the Iso group and FF pretreatment could
      significantly attenuate these changes (all P < 0.05). CONCLUSION: Our data
      suggested that the FFA utilization was decreased in Iso induced acute myocardial
      ischemic injury and FF could attenuate Iso induced myocardial damage via
      activating PPARalpha signaling pathway.

PMID- 19102874
TI  - [A case of very late stent thrombosis and self-thrombolysis after implantation of
      drug eluting stent (no abstract)].

PMID- 19102875
TI  - [Coronary arteries aneurysmal dilatation and thrombosis in a young man (no
      abstract)].

PMID- 19102876
TI  - [Mitochondria as an important target for prevention and treatment of heart
      failure (no abstract)].

PMID- 19102877
TI  - [The Pro-arrhythmic effects and prevention of transmural dispersion of
      repolarization during cardiac resynchronization therapy (no abstract)].

PMID- 19102879
TI  - [Universal definition of myocardial infarction: implication and concern.].

PMID- 19102881
TI  - [Cardiac troponin measurement in clinical practice.].

PMID- 19102880
TI  - [Recommendation of the application of universal definition of myocardial
      infarction in China.].

PMID- 19102882
TI  - [Cardiac and renal arteriolar pathological changes in the autopsied elderly
      hypertensive patients with left ventricular hypertrophy.].
AB  - OBJECTIVE: To determine the cardiac and renal arteriolar pathological changes in
      autopsied elderly hypertensive patients with left ventricular hypertrophy (LVH).
      METHODS: Autopsy samples from 25 essential hypertension (EH) patients with LVH
      aged over 60 years and age-matched 8 controls were analyzed. LVH was further
      divided into three degrees from I to III according to left ventricular free wall
      thickness in EH patients. Quantitative measurements of arteriolar morphometric
      parameters in heart and kidney were performed under light microscope with
      computer image analysis post HE and Masson staining. The lesion index and plasma
      albumen infiltration of arteriole were evaluated by the semiquantitative method.
      RESULTS: The inner diameter (ID) and luminal cross-sectional area (LCSA) were
      significantly decreased while wall thickness (WT), wall cross-sectional area
      (WCSA), ratio of WCSA to LCSA (WCSA/LCSA) and ratio of WT to ID (WT/ID) were
      significantly increased in EH patients in proportion to LVH degree. Both cardiac
      and renal arterioles WCSA/LCSA and WT/ID were significantly decreased with
      increasing outer diameters (OD). Under the same OD rang, the pathological changes
      were more significant in the renal arterioles compared to those in the cardiac
      arterioles (P < 0.05). The arteriolar lesion index and the plasma albumen
      infiltration index of cardiac and renal arterioles in EH group were significantly
      higher than those in the control group (P < 0.01) and the arteriolar lesion index
      and the plasma albumen infiltration of arteriole in the renal tissue were
      significantly higher than those in the cardiac tissue (P < 0.01). CONCLUSION:
      Concentric remodeling occurs in the cardiac and renal arterioles of EH patients
      in proportion to LVH degree and renal arterioles lesions were significantly
      severer than that of cardiac arterioles in EH patients with LVH.

PMID- 19102883
TI  - [Polymorphisms of D17S1878 and D17S932 on the Chromosome 17 and risk of essential
      hypertension.].
AB  - OBJECTIVES: To identify the possible relationship between polymorphisms of
      D17S1878 and D17S932 on the Chromosome 17 and risk of essential hypertension
      (EH). METHODS: The polymorphisms of D17S1878 and D17S932 were genotyped using
      Genetic Analyzer in 325 subjects from 67 Chinese families with EH in Liaoning
      province. The polymorphisms of D17S1878 and D17S932 sites were genotyped using
      Genetic Analyzer and GeneScan Software; PHASE2.1 Software was used in hyplotype
      analysis and affected sib pair analysis was used in linkage analysis. RESULTS: 61
      hyplotypes were found in the study population with 272 hypertensive and 53
      normotensive subjects and the frequency of haplotype H1 [(CA)(18)/(CA)(11)] in
      the hypertensive (15.4%) was significantly higher than that in the normotensive
      (6.3%, P < 0.05). Affected sib pair analysis could be applied in 180 subjects,
      the t values of the D17S1878 and D17S932 were 1.88 and 3.95, respectively (both P
      < 0.05) suggesting that the transitivity and consistency of the D17S1878 and
      D17S932 in sib pairs from the pedigrees were higher than expected (25%).
      CONCLUSION: The polymorphisms of D17S1878 and D17S932 were possibly linked with
      predisposing genes of essential hypertension.

PMID- 19102884
TI  - [Association between ADRA1A gene polymorphism and autoantibodies against the
      alpha1-adrenergic receptor in hypertensive patients.].
AB  - OBJECTIVE: To observe the association between ADRA1A gene polymorphism and
      autoantibodies against the alpha1-adrenergic receptor in hypertensive patients.
      METHODS: A total of 396 patients with essential hypertension admitted to our
      hospital were selected and autoantibodies in sera were detected by ELISA, and
      patients were divided into the autoantibody positive and negative group. Genomic
      DNA was extracted from erythrocytes obtained from EDTA-treated blood by the Blood
      DNA extraction kit. Gene polymorphisms were detected by ligase detection reaction
      (LDR), including rs574584, rs1048101, rs3739216 and rs3802241. The frequency of
      genotypes and haplotype were analyzed. RESULTS: The frequencies of detected
      genotypes between the autoantibody against the alpha1-adrenergic receptor
      positive group and negative group were similar (P > 0.05) while significant
      difference was in the frequencies of haplotypes (all P < 0.05). The frequencies
      of genotypes with rs1048101 (genotype C/C, C/T, P = 0.017) and rs3802241
      (genotype A/A, A/G, P = 0.004) were significant different in autoantibody
      positive group compared to negative group in patients with stage 2. CONCLUSION:
      ADRA1A gene polymorphism might correlate with the alpha1-adrenergic receptor
      autoantibody production in hypertensive patients.

PMID- 19102885
TI  - [Association of the beta2-adrenergic receptor gene C659G polymorphism and
      essential hypertension in Xinjiang Kazakans.].
AB  - OBJECTIVE: To investigate the relationship between human beta2-Adrenergic
      Receptor (ADRB2) gene C659G polymorphism and essential hypertension in Xinjiang
      Kazakans. METHODS: Polymerase chain reaction and restriction fragment length
      polymorphism (PCR-RFLP) methods were used to detect the C659G polymorphism of
      ADRB2 gene in 435 Kazakans including 273 hypertensives (EH) and 162 normotensives
      (NT) and genotype frequencies between EH and NT were analyzed. RESULTS: The
      genotype frequencies (CC, CG, GG) of the C659G allele were 85.75%, 13.79%, 0.64%
      respectively and the C659 and G659 allele frequencies were 7.36%, 92.64% in this
      cohort. The ADRB2 genotype distribution and the allele frequencies of C659 and
      G659 were significantly higher in EH than those in NT (all P < 0.05). The G
      allele is a risk factor contributed to hypertension (OR 12.37). After adjustment
      for age and BMI, the systolic and diastolic blood pressure levels were
      significant higher in CG + GG genotype group compared with CC genotype group (P <
      0.05). CONCLUSION: There was significant association between the C659G
      polymorphism of ADRB2 gene and essential hypertension in Xinjiang Kazakans
      suggesting a role of ADRB2 gene C659G polymorphism in the development of
      hypertension in Xinjiang Kazakans.

PMID- 19102886
TI  - [The relationship between dyslipemia and the polymorphism of angiotensin II type
      1 receptor gene in hypertensive Kazakans of Xinjiang.].
AB  - OBJECTIVE: To investigate the relationship between dyslipidemia and the
      polymorphism of angiotensin II type 1 receptor (AT(1)R) gene A1166C in
      hypertensive Kazakans of Xinjiang area. METHODS: Polymerase chain reaction and
      restriction fragment length polymorphism (PCR-RFLP) methods were used to detect
      the A1166C polymorphism of AT(1)R gene of 296 hypertensive and 198 normotensive
      Kazakans. Biochemical parameters were measured by autochemical emalyzer. RESULTS:
      (1) The TC and LDL-C levels are significantly higher in hypertension group than
      those in normotensive controls [TC: (4.91 +/- 1.19) mmol/L vs. (4.43 +/- 1.20)
      mmol/L; LDL-C: (3.36 +/- 1.01) mmol/L vs. (2.94 +/- 1.30) mmol/L, P < 0.001). (2)
      In hypertension group, TC and LDL-C are related to A1166C polymorphism of AT(1)R
      gene and TC and LDL-C of AC carriers are significantly higher than AA carriers (P
      < 0.05). CONCLUSION: The dyslipidemia is related to A1166C polymorphism of AT(1)R
      gene in hypertensive Kazakans.

PMID- 19102887
TI  - [Association between dysplastic development of ventricular wall and primary
      cardiomyopathy: pathomorphological observations on 92 hearts from transplant
      recipients.].
AB  - OBJECTIVE: To investigate the morphological characteristics and types of
      ventricular wall with dysplastic development and their associations to primary
      cardiomyopathy. METHODS: Ninety-two hearts from heart transplant patients were
      studied soon after explanation from 2004 to 2007. Gross examination/measurement,
      histopathology and photography were performed. RESULTS: Dysplastic development of
      ventricular wall could be evidenced in patients with various heart diseases but
      more often in patients with primary cardiomyopathy, though the extension and
      distribution of dysplastic development of ventricular wall varied between
      patients with or without primary cardiomyopathy. Severe dysplastic development of
      ventricular wall is associated with clinical dysplastic cardiomyopathy. The range
      of extension and degree of dysplasia in the ventricular wall correlated
      positively to heart dilation/failure and time point of heart failure development.
      The incidence of severe ventricular wall dysplasia was 27.17% in all transplanted
      hearts and was 43.1% (25/58) in hearts diagnosed as primary cardiomyopathy (P <
      0.05). The main pathological changes of dysplastic hearts were: (1) extensive
      proliferative hypertrophy of the heart wall, (2) fibrous/fat or fat/fibrous
      tissue replacement of normal myocardium, (3) disarrangement of myocardial fibers,
      (4) dysplastic change in the medium-sized intramural arteries. Dysplastic
      cardiomyopathy was presented mainly as a combination of several forms of
      dysplasia. The same clinical manifestations of dysplastic cardiomyopathy patients
      did not always show the same pathologic changes. Fibrous-fat tissue replacement
      was commonly found in dilated cardiomyopathy and arrhythmogenic right ventricular
      cardiomyopathy. Disarrangement of myocardium was often accompanied by
      hypertrophic cardiomyopathy. Dysplasia of intramural arteries could result in
      heart dilatation due to myocardial ischemia. CONCLUSION: Dysplasia of ventricular
      wall is a common variation of heart structure. Only severe or diffuse types of
      dysplasia is associated with cardiomyopathy, especially primary cardiomyopathy.

PMID- 19102888
TI  - [Outcome of patients with coronary artery disease underwent carotid artery
      stenting before coronary artery bypass surgery.].
AB  - OBJECTIVE: To evaluate the safety and efficacy of carotid artery stenting before
      open heart surgery. METHODS: Patients with heart disease and severe carotid
      artery stenosis received carotid stenting before open heart surgery were included
      in this prospective cohort study. The incidence of stroke, myocardial infarction
      and death from carotid stenting to 30 days after cardiac surgery was assessed.
      RESULTS: A total of 42 patients were enrolled. The carotid stenting procedural
      success rate was 100%. Distal embolic protection devices were used in 97.6%
      patients (41/42). Thirty-six (85.7%) patients received bypass surgery, 5 patients
      received bypass and valve replacement surgery (11.9%) and 1 patient received
      valve replacement surgery (2.4%) post carotid stenting. The incidence of stroke,
      myocardial infarction and death from carotid stenting to 30 days after cardiac
      surgery was 2.4% (1/42), 0% and 0% respectively. CONCLUSIONS: Our data from this
      small cohort study showed that carotid artery stenting before open heart surgery
      was safe and effective for patients with heart disease and severe carotid artery
      stenosis.

PMID- 19102889
TI  - [Quantitative evaluation of ischemic myocardium by adenosine tissue Doppler
      stress echocardiography.].
AB  - OBJECTIVE: To evaluate the value of adenosine tissue Doppler stress
      echocardiography on ischemic myocardium. METHODS: Routine dosage (140 microgxkg(
      1)xmin(-1) IV for 6 min) adenosine stress echocardiography was performed on 40
      patients with chest pain for diagnosis of coronary artery disease (CAD). The
      images of left ventricular myocardial motion were acquired by tissue Doppler
      imaging (TDI) based on traditional 2D stress echocardiography before and 3 min, 6
      min after adenosine stress (GE Vivid 7, USA). The myocardial velocity, strain and
      strain rate in 16 segments were offline measured and analyzed on ECHOPAC
      software. The results were compared with that of coronary angiography (CAG).
      RESULTS: CAG identified 18 CAD and 22 non-CAD patients with 159 ischemic segments
      and 465 non-ischemic segments. Adenosine significantly increased the systolic
      velocity (Sm), early diastolic velocity (Em), late diastolic velocity (Am), peak
      systolic strain (Smax), systolic strain rate (SRs), early diastolic strain rate
      (SRe) and late diastolic strain rate (SRa) both ischemic and non-ischemic
      segments (all P < 0.05). The baseline Sm and Em in ischemic segments were
      significant lower than non-ischemic segments [(3.16 +/- 1.20) cm/s vs (4.03 +/-
      1.27) cm/s, P < 0.01; (3.75 +/- 1.67) cm/s vs (4.66 +/- 1.70) cm/s, P < 0.05]. At
      peak stress the differences in Sm and Em were more significant [(3.98 +/- 1.63)
      cm/s vs (5.07 +/- 1.52) cm/s; (4.51 +/- 2.32) cm/s vs (6.52 +/- 2.56) cm/s; P <
      0.01]. The reductions on Smax and Se were more significant in ischemic segments
      compared those in non-ischemic segments (16.91% +/- 3.35% vs 19.56% +/- 5.47%, P
      < 0.01 and 9.53% +/- 2.89% vs 13.06% +/- 4.63%, P < 0.001). The biggest area
      under curve (AUC) in peak stress was seen in Se by ROC curve analysis (AUC =
      0.740, with sensitivity 67% and specificity 83%). CONCLUSION: Parameters derived
      from TDI offer reliable and accurate information on ischemic myocardium during
      adenosine stress echocardiography.

PMID- 19102890
TI  - [Association between plasma macrophage migration inhibitory factor concentration
      and coronary artery lesion severity.].
AB  - OBJECTIVE: To investigate the relationship between the plasma macrophage
      migration inhibitory factor (MIF), activator protein-1 (AP-1) and MMP-9
      concentrations and the severity of coronary artery lesions in coronary heart
      disease (CHD) patients. METHODS: Patients were divided into normal controls (n =
      35), stable angina pectoris (SAP, n = 32) and acute coronary syndrome (ACS, n =
      75) according to the coronary angiography (CAG), clinical and laboratory
      examinations. The CAG severity and extent of coronary lesions were analyzed by
      means of Gensini coronary score system. Enzyme linked immunosorent assay was used
      to measure the plasma MIF, AP-1 and MMP-9 concentrations. RESULTS: Plasma MIF, AP
      1 and MMP-9 concentrations were significant increased in CHD patients [MIF:
      (14.97 +/- 2.11) microg/L, AP-1: 1.43 +/- 0.33, MMP-9: (1.48 +/- 0.14) microg/L]
      compared to those in control group [MIF: (9.07 +/- 1.28) microg/L, AP-1: 0.71 +/-
      0.13, MMP-9: (1.01 +/- 0.07) microg/L, all P < 0.05]. The MIF, AP-1 and MMP-9
      concentrations in ACS group [MIF: (16.66 +/- 2.56) microg/L, AP-1: 1.56 +/- 0.22,
      MMP-9: (1.58 +/- 0.14) microg/L] were also significant higher than those in SAP
      group [MIF: (11.01 +/- 2.12) microg/L, AP-1: 1.04 +/- 0.25, MMP-9: (1.25 +/-
      0.07) microg/L, all P < 0.05] and there was significant positive correlation
      between MIF, AP-1 and MMP-9 concentrations and the Gensini score of coronary
      artery lesions (all P < 0.05). AP-1 was positively correlated with MMP-9 in CHD
      patients (P < 0.05). CONCLUSIONS: Plasma MIF, AP-1 and MMP-9 concentrations were
      positively correlated to the severity of coronary lesions in CHD patients. Higher
      MIF, AP-1 and MMP-9 concentrations in ACS patients than in SAP patients might
      suggest higher plaque instability in ACS patients.

PMID- 19102891
TI  - [Pericardial endothelin secretion in patients underwent open heart surgery.].
AB  - OBJECTIVE: To evaluate pericardial endothelin (ET) secretion by the human
      pericardial mesothelial cells. METHODS: Plasma, pericardial fluid and pericardial
      tissue were obtained in 51 patients receiving open heart surgery (coronary artery
      bypass grafting, elective heart valvuloplasty or valve replacement). ET
      concentrations in the plasma, pericardial fluid and pericardial tissues were
      measured by radioimmunoassay (RIA). ET mRNA expression in the human pericardium
      was detected by in situ hybridization. RESULTS: (1) The levels of ET in human
      pericardial fluid was significantly higher than that in the plasma [(128.8 +/-
      44.0) ng/L vs. (93.7 +/- 28.6) ng/L, P < 0.001]; (2) ET concentration in the
      pericardial tissue was (510.3 +/- 156.7) ng/kg; (3) In situ hybridization
      technique evidenced the abundant ET mRNA expression in human pericardial
      mesothelial cells. CONCLUSION: The study indicated that pericardium secreted ET
      into the pericardial space.

PMID- 19102892
TI  - [In Process Citation].

PMID- 19102893
TI  - [In vivo noninvasive detection of vulnerable atherosclerotic plaque by (99)Tc(m)
      Annexin V imaging in an atherosclerotic rabbit model.].
AB  - OBJECTIVE: Apoptosis contributes to the instability of the atherosclerotic (AS)
      lesions. The vulnerable plaque was identified in vivo by detecting the apoptosis
      with radiolabeled annexin V in an atherosclerotic rabbit model. METHODS: Eight
      male New Zealand white rabbits on 2% cholesterol diet for 2 weeks had abdominal
      aortic balloon injury and fed a 2% cholesterol diet for another 15 weeks (AS
      group), 3 rabbits fed a normal rabbit chow for 17 weeks without balloon injury
      served as controls. Annexin V labeled with (99)Tc(m) was then intravenously
      administered and planar whole-body images were captured using a gamma camera in
      the left lateral position. The entire length of the abdominal aorta was explanted
      for ex vivo imaging with gamma camera. The aorta then was divided into several
      segments according to the severity of AS. The segments were separated weighted
      and counted in an gamma counter for the absorptive dose of annexin per gram of
      tissue. Histology examinations were made on specimens. RESULTS: At 2 hours post
      annexin V injection, clear delineation of radiolabel within the abdominal aorta
      could be evidenced in vivo gamma imaging. After explanation of the aorta, ex vivo
      imaging showed a robust uptake of radiotracer in the infradiaphragmatic aorta
      corresponding to the in vivo images and conforming to the macroscopic
      distribution of atherosclerotic lesions. The uptake of radiolabel was absent in
      areas without grossly visible atherosclerotic lesions. The in vivo and ex vivo
      images identified plaque areas were identical and corresponded histological
      results on the explanted specimen. The aortic specimen was divided into 18
      segments on lesions. The magority of the lesions (14/18) manifested as type IV or
      type V lesions of AHA classification (vulnerable lesions), except segments 1 - 4,
      which manifested as type I or type II lesions. The thickness of fibrous cap (TFC)
      and the ratio of cap and lipid nuclear (RCN) were significantly reversely
      correlated to the unit radioactivity counts, and the correlation between RCN and
      the unit radioactivity counts was more significant than that between TFC and the
      unit radioactivity counts (r = -0.904, P < 0.01, and r = -0.8, P < 0.01).
      Apoptosis detection (TUNEL): annexin V intake in plaques was positively
      correlated to apoptotic index(r = 0.651, P = 0.012). CONCLUSION: Noninvasive
      Annexin V imaging could be used to detect vulnerable atherosclerotic plaques in
      vivo.

PMID- 19102894
TI  - [Disturbed shear stress affects disposition of caveolin-1 in endothelial cells.].
AB  - OBJECTIVE: To observe the distribution and expression changes of caveolin-1 under
      shear stress in a turbulence flow channel model mimicking susceptible sites of
      atherosclerosis in vitro. METHODS: Human umbilical vein endothelial cells
      (HUVECs) were inoculated to flow channel and then exposed to disturbed shear
      stress for 6, 12, 24 and 48 hours, respectively. HUVECs inoculated to flow
      channel without shear stress served as controls. Immunofluorescence staining was
      performed with SABC-FITC to detect the caveolin-1 distribution and RT-PCR was
      used to determine the mRNA expression of caveolin-1 gene in these cells. RESULTS:
      Confocal microcopy revealed ellipse-like shaped HUVECs under disturbed shear
      stress and caveolin-1 didn't move toward to the upstream edge of HUVECs but moved
      toward to the edge of HUVECs, and expression of caveolin-1 gene in HUVECs was
      significantly downregulated after exposure to shear stress for 48 hours compared
      to HUVECs without shear stress stimulation. CONCLUSION: Disturbed shear stress
      affected disposition and expression of caveolin-1 which might be responsible for
      shear stress induced endothelial cell pathological atherosclerotic changes.

PMID- 19102895
TI  - [Time course of ubiquitin and rat component 3 of proteasome expressions and
      association with common carotid artery intimal proliferation after balloon injury
      in rats.].
AB  - OBJECTIVE: To investigate the dynamic ubiquitin and rat component 3 of proteasome
      (RC3) change and association with intimal proliferation in the common carotid
      artery of rats after balloon injury. METHODS: Male SD rats were randomly divided
      into two groups: sham operation group (n = 8), ballon injury group at various
      time points (1, 4, 7, 14, 21, 28-days post injury, n = 8 each). The balloon
      injury model was established by deendothelializing the rat common carotid aortic
      artery by inflated 2F balloon catheter. HE staining was used to observe the ratio
      of intima-media (I/M) thickness of the injured arteries under optical microscopy.
      The expression levels of ubiquitin and RC3 mRNA were detected with RT-PCR. The
      expression level of ubiquitin protein was measured by immunohistochemistry
      method. RESULTS: The maximal intimal proliferation and peak intima-media ratio
      (2.31 +/- 0.43 vs. control 0.02 +/- 0.005, P < 0.01) were seen at 28th day post
      injury. The peak expression of ubiquitin was observed at the 7th day post injury
      (1.33 +/- 0.26 vs. control 0.21 +/- 0.04, P < 0.01) and peak RC3 expression was
      found at the 14th day post injury (1.35 +/- 0.26 vs. control 0.31 +/- 0.06, P <
      0.01). The protein expression of ubiquitin was also seen at the 14th day post
      injury (21.53 +/- 4.09 vs. control 4.21 +/- 0.78, P < 0.01). The expression of
      ubiquitin protein was positively correlated with intimal proliferation(r = 0.827,
      P < 0.05). CONCLUSION: The upregulated ubiquitin and RC3 expressions after
      balloon injury might play an important role in intimal proliferation in this
      model.

PMID- 19102896
TI  - [Effects of hepatocyte growth factor gene transfer in combination with
      echocardiographic destruction of microbubbles in a rat model of experimental
      myocardial infarction.].
AB  - OBJECTIVE: To evaluate whether ultrasonic microbubble destruction (US/MB) could
      enhance the therapeutic effects of hepatocyte growth factor (HGF) gene transfer
      for acute myocardial infarction (MI). METHODS: MI was induced by left anterior
      descending artery ligation in male SD rats. Two to 4 hours thereafter, MI rats
      were randomly treated with tail vein infusing pc-DNA3.1-HGF plasmid mixed with
      microbubbles (US/MB-HGF group, n = 18); tail vein infusing pc-DNA3.1-HGF plasmid
      mixed with saline (US-HGF group, n = 18); tail vein infusing empty plasmid mixed
      with microbubbles (US/MB-P group, n = 18). All rats were exposed to ultrasound
      treatment thereafter till contrast imaging disappeared in cardiac region. Rats
      were sacrificed at 24 hours, 7 days or 14 days, respectively (n = 6 each) and
      myocardial protein expression of bcl-2 and HGF as well as microvascular density
      (MVD) were determined. RESULTS: The myocardial protein expressions of bcl-2 and
      HGF in US/MB-HGF group were significantly higher than those in US-HGF and US/MB-P
      groups at 7 days post MI (all P < 0.01) and MVD was significantly higher in US/MB
      HGF group (367.6 +/- 17.6) than that in US-HGF (268.9 +/- 0.8) and US/MB-P (186.8
      +/- 11.8) groups (all P < 0.05) at 14 days post MI. CONCLUSIONS: Ultrasound
      mediated microbubble destruction could enhance systemic HGF administration
      induced myocardial angiogenesis and reduce systemic HGF administration induced
      myocardial apoptosis in rats with acute MI.

PMID- 19102897
TI  - [Serum triglyceride is an independent risk factor for acute coronary heart
      disease events in 35 - 64 years old Chinese-Chinese Multi-provincial Cohort
      Study.].
AB  - OBJECTIVE: To evaluate the association between serum triglyceride (TG) and the
      cardiovascular diseases (CVD) risk in Chinese population. METHODS: A total of 30,
      378 men and women aged 35 - 64 years old were recruited in the Chinese-Chinese
      Multi-provincial Cohort Study (CMCS). The serum TG and other CVD risk factors
      were measured. All subjects were followed up annually or biannually for acute CVD
      events from 1992 to 2004. A Cox regression model was established to identify the
      association between TG and risk of CVD events. RESULTS: The accumulative
      incidence rate of acute coronary heart disease (CHD) events increased from
      62.6/100 000 in the low TG groups to 168.4/100 000 in the high TG group divided
      by the quartile. TG was identified as an independent risk factor for CHD after
      adjustment for the confounding risk factors by a Cox regression model. Compared
      subjects with TG < 0.81 mmol/L, CHD risk increased 81% and 59% in subjects with
      TG 1.15 - 1.59 mmol/L and TG >/= 1.60 mmol/L, respectively (all P < 0.05). There
      was no significant association between TG level and the risks of hemorrhagic and
      ischemic stroke events (P > 0.05). CONCLUSION: Serum TG is an independent risk
      factor for acute CHD events in Chinese population aged 35 - 64.

PMID- 19102898
TI  - [Cardiac field potentials and activation sequence in Langendorff perfused heart,
      cardiac tissue slices and cultured ventricular myocytes recorded by
      microelectrode arrays system.].
AB  - OBJECTIVE: To observe field potentials (FPs) and activation sequence at
      Langendorff perfused guinea pigs heart, SD rat cardiac tissue strips perfused by
      Tyrode's solution and cultured ventricular cardiomyocytes of suckling mice by
      microeletrode arrays (MEA) technique. METHOD: FPs and activation sequence were
      recorded from perfused heart, cardiac tissue strips (5 mm x 5 mm) and cultured
      ventricular cardiomyocytes by MEA. RESULTS: (1) FPs could be recorded in hearts
      perfused for 30 to 90 min with a heart rate 90 - 120 beats/min. FP durations of
      both ventricular and atrial tissue were (210 +/- 78) ms and (164 +/- 58) ms,
      respectively and atrial ventricular conduction time was (320 +/- 150) ms. (2) The
      excitability of Tyrode's solution perfused tissue strips was visible for more
      than 2 h, and FP durations of ventricular and atrial tissue strips were (115.80
      +/- 11.61) ms and (83.71 +/- 6.48) ms, respectively. (3) Spontaneous beating
      frequency (150 +/- 100) beats/min and FPs could be readily recorded in
      cardiomyocytes cultured between 2 to 72 hours. CONCLUSION: MEAs is a sensitive,
      low noise and stable technique for observing local tissue action potential and
      activation sequence of whole heart, cardiac tissue strips and cultured
      cardiomyocytes.

PMID- 19102899
TI  - [A case of misdiagnosis of acute inferior myocardial infarction in patient with
      meningiomas and dextroversion(no abstract).].

PMID- 19102900
TI  - [Research and developments of antihypertensive vaccines(no abstract).].

PMID- 19102902
TI  - [Advances in congenital long QT syndrome(no abstract).].

PMID- 19102901
TI  - [Clinical progress of endothelin receptor antagonists therapy for pulmonary
      arterial hypertension(no abstract).].

PMID- 19102903
TI  - [In Process Citation].

PMID- 19102904
TI  - [Recognizing the proper usage of imaging modalities in diagnosis of coronary
      heart disease].

PMID- 19102905
TI  - [Clinical application of magnetic resonance in cardiovascular disease].

PMID- 19102906
TI  - [Advances in technologies and clinical application of multislice spiral CT for
      cardiovascular diseases].

PMID- 19102907
TI  - [Assessment of therapeutic effects of stem cell transplantation in heart failure
      patients with old myocardial infarction by magnetic resonance imaging].
AB  - OBJECTIVE: To evaluate the therapeutic effects of stem cell transplantation in
      heart failure patients with old myocardial infarction (OMI) by MRI. METHODS:
      Heart failure patients [NYHA 2.7 +/- 0.7, male = 18, mean age (59.5 +/- 10.1) y]
      with OMI were randomly divided into 2 groups (group A: CABG + stem cell
      transplantation, group B: CABG; n = 10 each). Left ventricular (LV) function was
      measured by MRI, viable myocardium was detected by (18)F-FDG myocardial
      metabolism imaging and late contrast-enhanced at baseline and 6 months post
      intervention. RESULTS: LVEF and LVEDV at baseline for group A were (20.71 +/-
      6.09)% and (172.73 +/- 32.74) ml, and for group B were (27.59 +/- 2.31)% and
      (155.13 +/- 28.36) ml, respectively (P > 0.05). The LVEF was equally improved in
      group A and B (mean 8.63% vs. 10.37%, P > 0.05) while DeltaLVEDV was significant
      higher in group A than that in group B [(9.91 +/- 39.50) ml vs. (-22.34 +/-
      31.35) ml, P < 0.05]. Ventricular wall thickening ratio at 6 months post
      intervention was significantly higher in group A than that in group B [(11.40 +/-
      11.53)% vs. (2.27 +/- 7.20)%, P < 0.05]. Late contrast-enhanced MRI results
      correlated with (18)F-FDG myocardial metabolism imaging SPECT well in assessment
      of myocardial viability (kappa value: 0.446, P < 0.001; sensitivity: 68.3% and
      specificity: 92.5%). CONCLUSIONS: Stem cell therapy on top of CABG aggravated LV
      remodeling in heart failure patients with old myocardial infarction. The
      specificity of MRI is similar to (18)F-FDG SPECT while the sensitivity is
      inferior to (18)F-FDG SPECT on detecting viable myocardium.

PMID- 19102908
TI  - [Morphological characteristics of ostial and non-ostial left main coronary artery
      lesion without heavy calcification determined by intravascular ultrasound
      imaging].
AB  - OBJECTIVE: We aimed to assess and compare the morphological characteristics of
      ostial and non-ostial left main coronary artery (LMCA) lesion without heavy
      calcification using intravascular ultrasound (IVUS) imaging. METHODS: Between
      Oct. 2004 and Oct. 2007, 153 patients with confirmed or suspected coronary artery
      narrowing in coronary angiography with satisfactory IVUS images and non-heavy
      calcification were included in the study (ostial lesions, n = 47; non-ostial
      lesion, n = 106). IVUS analysis included plaque composition, external elastic
      membrane (EEM), lumen, plaque cross-sectional area (CSA), plaque burden (plaque
      CSA/EEM CSA) at the lesion, proximal and/or distal reference site, and remodeling
      index (RI, lesion EEM CSA/reference EEM CSA). Negative remodeling was defined as
      RI < 0.95. RESULTS: LMCA mean reference lumen and vessel diameter was 4.1 +/- 0.8
      mm and 5.3 +/- 0.8 mm respectively. Incidence of patients with minimum lumen area
      (MLA < 6.0 mm(2)) was similar between the two groups (29.5% for ostial lesions
      and 31.9% for non-ostial lesions, P = 0.87). There were significantly more
      fibrous (70.2% vs. 35.8%) and soft (8.5% vs. 3.8%) plaques while significantly
      less calcified plaque (19.2% vs. 43.4%) in patients with hostile lesions compared
      those with non-ostial lesions (all P < 0.05). Compared to non-ostial lesions,
      ostial lesion had significant smaller plaque area [(10.8 +/- 4.5) mm(2) vs. (13.3
      +/- 5.4) mm(2), P = 0.007], less plaque burden (54.8% +/- 15.9% vs. 61.9% +/-
      14.5%, P = 0.020), smaller RI (0.9 +/- 0.2 vs. 1.0 +/- 0.2, P = 0.000) and higher
      incidence of negative remodeling (74.5% vs. 34.9%, P = 0.000). Multivariant
      Logistic regression analysis showed that the site of lesion (ostial or non-ostial
      lesion, OR = 4.9, P = 0.004), plaque area (OR = 1.2, P = 0.01) and plaque burden
      (OR = 0.003, P = 0.000) were the independent predictors of LMCA remodeling.
      CONCLUSION: Negative remodeling might be responsible for the development of LMCA
      ostial narrowing.

PMID- 19102909
TI  - [Combined use of optical coherence tomography and intravascular ultrasound during
      percutaneous coronary intervention in patients with coronary artery disease].
AB  - OBJECTIVE: To evaluate the value of combined optical coherence tomography (OCT)
      and intravascular ultrasound (IVUS) examinations in detecting coronary artery
      plaque during percutaneous transluminal coronary intervention (PCI). METHODS: OCT
      and IVUS examinations were performed on 30 diseased coronary vessels from 27
      patients underwent PCI from Feb. 2008 to July. 2008. RESULTS: Seventeen
      vulnerable plaques (4 intima tearing which were not detected by IVUS), 5 plaque
      rupture (1 out of 5 was detected by IVUS), 5 thrombus lesions (1 out of 5 was
      found by IVUS), 12 thin-cap lipid-rich lesions (2 detected by IVUS) were detected
      by OCT in 22 lesions (without 8 lesions post DES stents). Analysis result of
      plaque burden by IVUS was superior to that obtained by OCT. In 8 DES stents
      (implanted for 6 months to 4 years), OCT detected 2 had severe restenosis, 6
      stents struts were completely covered with neointima without restenosis, 1 stent
      had aneurysm-like dilatation. IVUS results were similar except for limitations on
      exactly detecting neointima post stenting. In 19 newly implanted stents, the
      incidence of stent under-expansion detected by OCT was 26.0% (same as that by
      IVUS), stent malposition was 63.2% (10.5% by IVUS, P < 0.01), near stent tearing
      was 10.5% (not detected by IVUS), tissue prolapse between coronary stent struts
      was 52.6% (10.5% in IVUS, P < 0.05). CONCLUSIONS: OCT imaging is superior to IVUS
      on detecting vulnerable plaques and change of structure around stents while IVUS
      is superior to OCT on estimating plaque burden in patients underwent PCI.

PMID- 19102910
TI  - [Diagnostic performance of prospective versus retrospective electrocardiogram
      gated 64-slice computed tomography coronary angiography].
AB  - OBJECTIVE: To compare the diagnostic performance of prospective electrocardiogram
      (ECG)-triggered computed tomography coronary angiography (CTCA) versus
      retrospective ECG-gated CTCA. METHODS: Patients with suspected coronary artery
      disease divided into two groups which underwent 64-slice CTCA with prospective
      ECG-triggered or retrospective ECG-gated scanning (n = 100 each, HR < or = 65
      bpm). Multi-planar reconstruction (MPR), curved-planar reconstruction (CPR),
      maximum intensity projection (MIP) and volume rendering (VR) were made to
      demonstrate the coronary arteries. The image quality was defined as excellent,
      good and poor by motion and stair-step artifacts. Individual radiation exposure
      dose was estimated from the dose-length product. RESULTS: The mean effective
      radiation dose of prospective ECG-triggered CTCA [(2.81 +/- 0.48) mSv] was
      significantly lower than that of retrospective ECG-gated CTCA [(10.16 +/- 1.09)
      mSv, P < 0.01]. Segments of diagnostic image quality (95.2%, 1165/1224) and non
      diagnostic coronary segments (4.8%, 59/1224) in prospective ECG-triggered group
      were similar as those of retrospective ECG-gated group (94.1%, 1186/1261 and
      5.9%, 75/1261, all P > 0.05). CONCLUSION: Though the radiation exposure dose
      required is significantly lower, the diagnostic performance of prospective ECG
      triggered 64 slice CTCA is comparable with that of retrospective ECG-gated 64
      slice CTCA on patients with stable heart rates up to 65 bpm.

PMID- 19102911
TI  - [Value and limitations of multislice spiral CT in diagnosing coronary artery
      stenoses].
AB  - OBJECTIVE: To evaluate the value and limitations of multislice spiral CT in
      diagnosing coronary artery stenoses. METHODS: A total of 65 patients with known
      or suspected coronary artery disease were examined by multislice spiral CT
      (retrospectively ECG-gating; 0.5 s rotation; one-sector reconstruction algorithm;
      intravenous contrast agent) and the results were compared with quantitative
      coronary angiography. RESULTS: In the 889 coronary artery segments of 65
      patients, 795 could be evaluated by CT (89.4%), 148 out of 167 coronary artery
      segments with significant stenoses (> or = 50% reduction of vessel diameter) were
      correctly detected by CT, 597 out of 628 coronary artery segments with normal or
      mild stenosis (< 50% reduction of vessel diameter) were correctly detected by CT.
      These values correspond to a sensitivity of 88.6%, specificity of 95.1%, positive
      predictive value of 82.7%, and negative predictive value of 96.9% for the
      detection of significant coronary artery stenosis by CT. Adding the 23 coronary
      artery segments with significant stenosis which could not be judged by CT, the
      sensitivity of CT for diagnosing coronary stenosis was 77.9%. In the 795
      evaluable coronary artery segments, 78 out of 86 coronary artery segments with
      high-grade stenosis (> or = 75% reduction of vessel diameter) were correctly
      detected by CT, 692 of 709 coronary artery segments with normal or mild stenosed
      (< 75% reduction of vessel diameter) were correctly detected by CT. These values
      correspond to a sensitivity of 90.7%, specificity of 97.6%, positive predictive
      value of 82.1%, and negative predictive value of 98.9% for the detection of high
      grade coronary artery segments stenosis by CT. Adding 13 coronary artery segments
      with high-grade stenosis which could not be judged by CT, the sensitivity was
      78.8%. CONCLUSION: Multislice spiral CT permits the visualization of significant
      coronary artery stenosis with high accuracy in case of sufficient image quality.

PMID- 19102912
TI  - [Comparison of coronary plaque composition between patients with acute coronary
      syndrome and stable coronary artery disease].
AB  - OBJECTIVE: The purpose of the present study was to compare the plaque composition
      between patients with acute coronary syndrome (ACS) and stable coronary artery
      disease (SCAD) by intravascular ultrasound virtual histological analysis.
      METHODS: Two hundred and ten patients were divided into ACS group (n = 131, 188
      diseased vessels) and SCAD group (n = 79, 158 diseased vessels). A total of 346
      de novo lesions with > 50% stenosis in native coronary arteries with diameters >
      2.5 mm were studied with intravascular ultrasonography. Geometric and
      compositional data were obtained using intravascular ultrasound virtual histology
      software. RESULTS: There were no significant differences in overall lesions for
      fibrous (51.2% +/- 12.5% vs. 52.6% +/- 9.6%), fibrolipidic (11.3% +/- 10.6% vs.
      12.9% +/- 9.4%), calcium (15.1% +/- 8.9% vs. 20.5% +/- 12.5%) or necrotic core
      (23.1% +/- 9.8% vs. 20.4% +/- 6.8%, all P > 0.05) components between ACS and SCAD
      patients. Culprit lesions for fibrous (49.1% +/- 11.2% vs. 50.3% +/- 9.7%),
      fibrolipidic (10.2% +/- 9.5% vs. 12.7% +/- 9.5%), calcium (15.4% +/- 8.9% vs.
      17.4% +/- 24.8%), or necrotic core (24.0% +/- 11.5% vs. 19.7% +/- 5.3%, all P >
      0.05) components were also similar between ACS and SCAD patients. High density
      lipoprotein-cholesterol (HDL) levels > 1.04 mmol/L was associated with more
      fibrolipidic (15.6% +/- 9.6% vs. 7.4% +/- 5.9%) and less necrotic core (19.4% +/-
      8.6% vs. 28.6% +/- 11.2%, all P < 0.05 vs. patients with HDL < or = 1.04 mmol/L)
      components in ACS patients. CONCLUSION: Coronary plaque composition was similar
      between ACS and SCAD patients.

PMID- 19102913
TI  - [Impact of viable myocardium assessed by 99Tcm-MIBI SPECT and 18F-FDG PET imaging
      on clinical outcome of patients with left ventricular aneurysm underwent
      revascularization].
AB  - OBJECTIVE: To evaluate the impact of viable myocardium assessed by (99)Tc()m-MIBI
      SPECT and (18)F-fluorodeoxyglucose (FDG) PET imaging in patients with left
      ventricular aneurysm (LVA) underwent revascularization (RVS). METHODS: Forty-six
      consecutive patients with LVA (mean LVEF 36% +/- 7%), underwent (99)Tc(m)
      sestamibi SPECT and (18)F-FDG PET examinations and received RVS therapy, were
      followed-up for a mean period of 80 +/- 27 months. Viable myocardium in aneurysm
      was defined as perfusion-metabolism mismatch score (MMS) >/= 2.0. Patients were
      divided into four groups by aneurysm viability and aneurysmectomy. Group A1 (n =
      8): viability-; Group A2 (n = 15): viability-, aneurysmectomy; Group B1 (n = 10):
      viability +; and Group B2 (n = 13): viability +, aneurysmectomy. RESULTS: The
      cardiac event rates during follow up were similar among groups [A1 (25%, 2/8), B1
      (40%, 6/15), A2 (20%, 2/10) and B2 (31%, 4/13; P > 0.05)]. After
      revascularization, LVEF was improved (> 10%) in groups A2, B1 and B2 (P < 0.05).
      Multivariate logistic regression analysis showed that LV-MMS (OR = 2.34, 95% CI
      1.08 - 5.06, P < 0.05), distal vessel disease (OR = 0.008, 95% CI 0.001 - 0.560,
      P < 0.05) and nonaneurysm perfusion score (OR = 0.24, 95% CI 0.07 - 0.85, P <
      0.05) were significantly associated with the improvement of LVEF after
      revascularization. CONCLUSIONS: Long term cardiac events rate post
      revascularization was not affected by viable myocardium or aneurysmectomy in LVA
      patients. Viable myocardium in LVA patients was associated with better LVEF
      improvement after revascularization.

PMID- 19102914
TI  - [Therapeutic effects of magnetically labeled mononuclear and mesenchymal stem
      cells transplantation in a swine myocardial infarction model assessed by magnetic
      resonance imaging].
AB  - OBJECTIVE: To evaluate the therapeutic effects of magnetically labeled
      mononuclear stem cells (MR-MNC) and mesenchymal stem cells (MR-MSC)
      transplantation in a swine acute myocardial infarction (AMI) model by MR imaging.
      METHODS: AMI model was established in swines by balloon occlusion of the left
      anterior descending coronary artery, 10(7) autologous MR-MSC (n = 7), MR-MNC (n =
      6) or PBS (n = 6) were delivered via intracoronary infusion within 1 week after
      AMI [(4.8 +/- 1.3) days]. Changes of infarct size and cardiac function were
      assessed with the use of 3.0T MR scanner before AMI, at 1 and 8 weeks post AMI.
      RESULTS: Magnetically labeled stem cells could be identified in the region of AMI
      by cardiac MR imaging. Eight weeks post transplantation, infarct size was
      significantly reduced in MR-MSC transplantation group (8.5% +/- 0.5% vs. 24.7% +/
      3.1%, P < 0.05) and in MR-MNC transplantation (12.3% +/- 1.5% vs. 26.1% +/-
      1.5%, P < 0.05) while infarct size remained unchanged in PBS group (P > 0.05)
      compared to values at 1 week post AMI, left ventricular ejection fraction (LVEF)
      was also significantly higher in MR-MSC transplantation group (56.9% +/- 1.3% vs.
      40.7% +/- 2.0%, P < 0.05) and MR-MNC transplantation group (52.8% +/- 1.4% vs.
      41.9% +/- 3.3%, P < 0.05) compared to LVEF at 1 week post AMI. LVEF increase was
      more significant in swines received MR-MSC transplantation than MR-MNC
      transplantation (16.2% +/- 1.2% vs. 10.9% +/- 3.0%, P < 0.05). Prussian blue
      staining identified stem cells in corresponding myocardial regions with as by
      MRI. Western blot analysis demonstrated that cardiac expressions of myosin heavy
      chain (MHC) in MR-MSC group (100.3 +/- 5.5) and in MR-MNCs group (95.5 +/- 4.2)
      were significantly higher than that in PBS group (75.7 +/- 5.7, P < 0.05),
      myocardial troponin T (cTNT) expression in MR-MSC group (124.0 +/- 5.8) and MR
      MNC group (118.4 +/- 4.4) were also significantly higher than in PBS group (93.3
      +/- 3.9, P < 0.05) while MMP2/TIMP1 ratios in MR-MSC group (0.6 +/- 0.1) and MR
      MNC group (0.6 +/- 0.1) were significantly lower than that in PBS group (4.2 +/-
      0.2, P < 0.05). CONCLUSIONS: Magnetically labeled MR-MSC and MR-MNC homed to
      heart post myocardial infarction and reduced infarct size, improved cardiac
      function. MR-MSC is superior to MR-MNC on improving cardiac function.

PMID- 19102915
TI  - [Mechanism and re-ablation strategy for postablation atrial tachyarrhythmia in
      atrial fibrillation patients].
AB  - OBJECTIVE: To investigate the mechanism and re-ablation strategy of recurrent
      atrial tachyarrhythmia (ATA) following circumferential ablation of pulmonary
      veins (PV) in patients with atrial fibrillation (AF). METHODS: Fifteen patients
      with recurrent ATA following first AF ablation procedure were included in this
      study. Under CARTO guidance, PVs were remapped and ablated subsequently for
      relapse of left atrium to PV conduction. The whole atrium was then remapped and
      individualized ablation was made to eliminate inducible ATA. RESULTS: Left atrium
      to PV conduction relapses were evidenced in 14 patients. After re-ablation, there
      were no inducible ATA in 9 patients, inducible left atrial macro-reentry
      tachycardia in 3 patients and all were terminated by further linear ablation on
      the roof and left atrial isthmus, inducible atrial focal tachycardia from left
      atrial isthmus in 1 patient and was eliminated after additional focal ablation,
      inducible right atrial macro-reentry tachycardia in 2 patients and were
      eliminated by right isthmus linear ablation. During 1 - 16 (5.5 +/- 4.4) months
      follow-up, ATA was disappeared in 13 patients and reduced in another 2 patients.
      CONCLUSIONS: Relapse of left atrium to PV conduction is one of the main
      mechanisms for postablation ATA in patients with AF. Atrial macro-reentry
      tachycardia and focal atrial tachycardia were less common mechanisms for
      postablation ATA. Re-ablation focused on closing the PV gaps and additional
      individualized focal and lineal ablation strategies were helpful for treating
      postablation ATA in AF patients.

PMID- 19102916
TI  - [Plasma tissue factor and tissue factor pathway inhibitor levels in acute
      myocardial infarction patients with no-reflow during percutaneous coronary
      intervention].
AB  - OBJECTIVE: To compare plasma tissue factor (TF) and tissue factor pathway
      inhibitor (TFPI) levels before, immediately and 24 hours after percutaneous
      coronary intervention (PCI) in acute myocardial infarction (AMI) patients with or
      without no-reflow. METHODS: Plasma TF and TFPI in AMI patients underwent PCI were
      measured by enzyme linked immunoadsorbent (ELISA) before, immediately and 24
      hours after PCI. RESULTS: The levels of TF and TFPI of no-reflow patients (n =
      17) were significantly higher than those of reflow patients (n = 36) at baseline,
      immediately and 24 hours after PCI [TF: (275.3 +/- 46.2) ng/L vs. (236.8 +/-
      44.3) ng/L, (332.7 +/- 41.3) ng/L vs. (282.3 +/- 38.7) ng/L, (315.5 +/- 47.8)
      ng/L vs. (248.1 +/- 46.9) ng/L; TFPI: (165.2 +/- 38.4) microg/L vs. (128.5 +/-
      18.7) microg/L, (176.3 +/- 36.8) microg/L vs. (135.6 +/- 20.3) microg/L, (149.8
      +/- 31.7) microg/L vs. (118.7 +/- 19.2) microg/L; all P < 0.01]. Plasma TF was
      significantly increased in both groups (all P < 0.01) immediately post PCI and
      the TF was still higher than that before PCI in no-reflow patients (P < 0.05) and
      returned to baseline level in reflow patients at 24 hours after PCI (P > 0.05),
      TFPI levels were similar before and after PCI in both groups (all P > 0.05).
      CONCLUSION: Plasma tissue factor and tissue factor pathway inhibitor might play
      important roles in the development of no-reflow during PCI in AMI patients.

PMID- 19102917
TI  - [Time course of myocardial NF-kappaB activation post coronary microembolization].
AB  - OBJECTIVE: To investigate the time course of myocardial NF-kappaB activation and
      association with cardiac function and other pro-inflammation cytokines following
      coronary microembolization (CME). METHODS: CME was induced by homologous
      microthrombotic particle suspension injection into left ventricle with
      simultaneous short-term ascending aorta clamping. The CME rats were randomized to
      untreated group and pyrrolidine dithiocarbamate (PDTC, a specific NF-kappaB
      inhibitor) treated group (n = 32 respectively). The rats were sacrificed on day
      1, 3, 7 and 14 post-operationally (n = 8 each). Twenty-four rats were sham
      operated and served as controls. NF-kappaB DNA-binding activity was evaluated by
      electrophoretic mobility shift assay (EMSA), protein expressions of TNFalpha, IL
      6 and ICAM-1 were analyzed by Western blotting, the dynamic alterations of
      TNFalpha, IL-6 and ICAM-1 mRNA were quantitatively assessed by Real-time PCR post
      hemodynamic measurements. RESULTS: NF-kappaB DNA-binding activity in CME group
      was significantly increased than that of sham group on day 1, peaked at day 3 and
      was similar as that in sham rats on day 14. The protein and mRNA expressions of
      TNFalpha, IL-6 and ICAM-1 were significantly increased in CME group at various
      time points compared those in sham rats. NF-kappaB DNA-binding activity
      positively correlated with mRNA expressions of TNFalpha, IL-6, ICAM-1,
      respectively (r = 0.72, P < 0.05; r = 0.94, P < 0.01; r = 0.62, P < 0.05). PDTC
      significantly suppressed protein and mRNA expressions of TNFalpha, IL-6 and ICAM
      1 (P < 0.05) and improved left ventricular function. CONCLUSION: NF-kappaB
      activation post CME could upregulate the gene transcriptions of TNFalpha, IL-6,
      ICAM-1 and enhance inflammatory responses and aggravate left ventricular
      dysfunction.

PMID- 19102918
TI  - [Heat shock protein 27 attenuated doxorubicin-induced myocardial damage by
      reducing cardiomyocyte apoptosis, mitochondria damage and protein carbonylation].
AB  - OBJECTIVE: Oxidative stress and apoptosis play a critical role in the
      pathogenesis of congestive heart failure (CHF) induced by doxorubicin (Dox) or
      ischemia/reperfusion. Heat shock protein 27 (Hsp27) could reduce oxidative stress
      induced apoptosis in various cell types in vitro and attenuate
      ischemia/reperfusion induced cardiac dysfunction in isolated perfused mouse
      heart. In this study, we investigated the impact of Hsp27 overexpression on
      oxidative stress and apoptosis in Dox-induced mice cardiac dysfunction model.
      METHODS: Both Hsp27 transgenic mice (TG) and wild type littermates (WT) received
      a single dosage of Dox (25 mg/kg IP) or saline. On day 3, histological
      examinations (Paraffin section and HE staining, mitochondria ultrastructure), in
      situ cardiomyocytes apoptosis assay (TUNEL, immunohistochemistry against alpha
      actinin for cardiomyocytes, hoechst33342 for nuclei staining), protein oxidative
      damage assay (immunoblot against DNP) were performed on cardiac tissue samples.
      Pleural effusion and histological changes of heart and lung were examined in dead
      mice. RESULTS: (1) Significant pleural effusion, pulmonary congestion, alveoli
      collapse and extravasated red blood cells were observed in all died mice. (2)
      Pronounced cardiomyocyte damages and inhomogeneous HE staining were observed in
      almost all dead mice except for one TG mouse died at day 4 which showed
      homogeneous HE staining and only slightly cardiomyocyte damages. (3) Cardiac
      fibrosis was presented in WT mice but not in TG mice. (4) Dox-induced
      cardiomyocyte apoptosis and protein carbonylation were significantly attenuated
      in TG mice compared those in WT mice. (5) Severity of Dox-induced mitochondria
      damage including increased density, swollen cristae and loss of cristae
      definition was significantly reduced in TG mice compared to that in WT mice were
      seen in all the examined myocytes of the LV myocardium samples of Dox-treated
      mice. CONCLUSION: Hsp27 could attenuate Dox-induced myocardial damage by reducing
      cardiomyocyte apoptosis, mitochondria damage and protein carbonylation.

PMID- 19102919
TI  - [Influence of various glucose levels on the structure and function of cultured
      neonatal rats cardiomyocytes].
AB  - OBJECTIVE: To study the influence of various glucose levels on the structure and
      function of cultured neonatal rats cardiomyocytes. METHOD: Cultured neonatal
      ventricular cardiomyocytes were treated with various glucose levels for 5 days:
      control (5.5 mmol/L); high (25.5 mmol/L); intermittent high (5.5 mmol/L or 25.5
      mmol/L in every 12 hours interval); high (25.5 mmol/L) + PKC inhibitor Ro-31-8220
      (50 nmol/L). Then, the cell beating frequency was counted, the cardiomyocytes
      diameters were measured and the expressions of PKC-alpha, PKC-beta(2), p-PKC
      alpha, p-PKC-beta(2), NF-kappaB and c-fos were determined by Western blot.
      RESULTS: Compared with control group, cardiomyocytes beating frequency, diameters
      as well as the expressions of PKC-alpha, PKC-beta(2), p-PKC-alpha, p-PKC-beta(2),
      NF-kappaB and c-fos were significantly increased in high glucose concentration
      (all P < 0.05) and intermittent high glucose treatment further amplified these
      changes (all P < 0.05 vs. high glucose and control groups). High glucose induced
      changes could be significantly attenuated with PKC inhibitor Ro-31-8220.
      CONCLUSION: High, especially intermittent high glucose could lead to diabetic
      cardiomyopathy by promoting cardiac hypertrophy, increasing beating frequency via
      activating PKC/NF-kappaB/c-fos pathways.

PMID- 19102920
TI  - [Nuclear receptor Nur77 inhibits oxidized low density lipoprotein induced lipid
      loading in macrophages].
AB  - OBJECTIVE: To observe the effect of Nur77 on lipid loading in macrophages exposed
      to 40 microg/ml oxidized low density lipoprotein (ox-LDL). METHODS: Stable
      RAW264.7 strain expressing green fluorescent protein (GFP) or GFP-Nur77 was
      established by G418 screening after transfection with corresponding plasmids and
      identified by Western blot. After 24 h stimulation with ox-LDL, intracellular
      lipid loading of each strain was observed by Oil Red O dyeing, and the
      intracellular cholesterol level was measured by liquid chromatographic-mass
      spectrometry (LC-MS). The transcriptional changes of CD36 and ABCA1 were
      monitored by Real Time Quantitative-PCR, while the expressions of these two
      proteins were assayed by flow cytometry and Western blot, respectively. RESULTS:
      After 24 h stimulation with ox-LDL, intracellular total cholesterol and
      esterified cholesterol concentration in GFP-Nur77-RAW264.7 were significantly
      dropped by 26.15% and 30.93% respectively (P < 0.05 vs. GFP-RAW264.7). The
      transcription and expression of ABCA1 in GFP-Nur77-RAW264.7 were significantly
      increased while the transcription and expression of CD36 were significantly
      reduced (all P < 0.05 vs. GFP-RAW264.7). CONCLUSION: Orphan nuclear receptor
      Nur77 reduced ox-LDL induced intracellular lipid loading in macrophages by
      inhibiting lipid influx and enhancing lipid efflux.

PMID- 19102922
TI  - [A case of pulmonary embolism with thrombus straddling between two atria
      diagnosed by echocardiography].

PMID- 19102921
TI  - [Association between hypertensive left ventricular hypertrophy and cardiovascular
      events in adult Beijing residents: a cohort study].
AB  - OBJECTIVE: To analyze the impact of hypertensive left ventricular hypertrophy
      (LVH) on cardiovascular events (CVD) in adult Beijing residents. METHODS: CVD
      risk factor survey was conducted in 7023 Beijing residents aged 25 - 64 by a
      stratified-random sample design from 1984 to 1993 in three years interval. CVD
      events were followed up and the association of the hypertensive LVH and risk of
      CVD and total death was analyzed by multivariable Cox Regression Model. All
      subjects were followed up to December 2004. RESULTS: There were 211 non
      hypertensive LVH patients in the cohort and were excluded from the study. (1)
      There were 2240 hypertensive patients among 6812 subjects on baseline. The total
      prevalence of LVH was 11.8% (16.1% in male and 7.5% in female). (2) Compared to
      the group with normal blood pressure and without left ventricular hypertrophy,
      subjects with hypertensive LVH had significantly higher risk for acute coronary,
      acute stroke, total CVD and total death rate. The relative risks (RR) were 4.92
      (95% CI: 2.3, 10.7), 4.2 (95% CI: 2.6, 7.0), 4.1 (95% CI: 2.6, 6.3) and 3.3 (95%
      CI: 2.0, 5.3), respectively. (3) Compared to the group with hypertension and
      without LVH, the group with hypertensive LVH had also significantly higher risk
      for acute stroke, total CVD and total death rate. The RR were 1.8 (95% CI: 1.1,
      2.8), 1.7 (95% CI: 1.2, 2.3) and 1.7 (95% CI: 1.1, 2.7), respectively. (4) The
      population attribute risks (PAR) of hypertensive LVH to the incidents of acute
      CHD, acute stroke, total CVD and total death were 13.0%, 11.0%, 10.4% and 7.9%,
      respectively. CONCLUSIONS: Hypertensive left ventricular hypertrophy was an
      independent risk factor for long term risk of cardiovascular events and death.

PMID- 19102924
TI  - [A case of systemic amyloidosis with cardiac involvement].

PMID- 19102925
TI  - [Molecular imaging for stem cell myocardial regeneration].

PMID- 19102926
TI  - [Gap junction and cardiac arrhythmias post stem cell therapy].

PMID- 19102927
TI  - [Effects of autophagy in myocardial ischemia and ischemia/reperfusion injury].

PMID- 19102930
TI  - [PET-CT-guided radiotherapy for non-small cell lung cancer].

PMID- 19102931
TI  - [Effect of nanosize delivery system for ASODN against hTERT on the expression of
      telomerase in the esophageal cancer EC9706 cells].
AB  - OBJECTIVE: To investigate the inhibitory effect of nanoparticle-mediated
      antisense oligodeoxynucleotide (ASODN) of human telomerase reverse transcriptase
      (hTERT) on telomerase in the esophageal cancer EC9706 cells. METHODS: Line
      polyethylenimine (L-PEI) was used to condense ASODN into nanoparticle and to
      couple NGR peptides into targeting nanoparticle, and the prepared L-PEI/ASODN
      complexes were transfected into the EC9706 cells. Cellular uptake of L-PEI/ASODN
      complexes was detected by laser confocal scanning microscopy. MTT assay was used
      to detect the inhibitory rate of EC9706 cell growth. The level of hTERT mRNA and
      its protein expression were measured by RT-PCR and immunohistochemistry,
      respectively. Annexin V FITC/PI double labeling was used to detect cell
      apoptosis. The distribution of drug in nude mice was observed by laser confocal
      scanning microscopy, and the growth and morphology of the tumor was examined.
      RESULTS: The L-PEI-mediated ASODN uptake was enhanced. After transfection, the
      inhibitory rate of EC9706 cells was time-dependant and there was a significant
      difference between control cell group and L-PEI/ASODN group (P < 0.05). At 48 h
      after transfection, the level of hTERT mRNA was decreased significantly compared
      with that of control cell group (P < 0.05), and the expression of hTERT protein
      was negative. There was apparent apoptosis in EC9706 cells after transfection
      with L-PEI/ASODN complexes. For the two NGR/L-PEI/ASODN groups, fluorescence was
      observed in the liver, kidney, lung and tumor tissues of nude mice, and their
      uptake intensity was time-dependent. The mean volume of tumors in the two NGR/L
      PEI/ASODN groups was significantly smaller than those in blank control group and
      SODN group (P < 0.05). Apoptotic bodies were detected in the tumors of L
      PEI/ASODN group. CONCLUSION: The NGR/L-PEI/ASODN nanoparticles can effectively
      reach into the human esophageal cancer xenograft and inhibit the tumor growth in
      nude mice, and this may provide a theoretical and experimental basis for gene
      therapy for human esophageal squamous cell carcinoma.

PMID- 19102932
TI  - [Differential gene expression of the inhibitor of apoptosis proteins in docetaxel
      resistant gastric cancer cells].
AB  - OBJECTIVE: Resistance to chemotherapy may indicate an unfavorable outcome for
      patients with gastric cancer. The purpose of this study was to examine whether
      docetaxel-resistance could be due in part to the expression of the inhibitor of
      apoptosis proteins (IAP). METHODS: Docetaxel-resistant cells, BGC-823/R1, BGC
      823/R2 and BGC-823/R3, were established from parent BGC-823 cells by stepwise
      increasing concentration of docetaxel. To characterize these cells, we examined
      the effects of docetaxel on cell growth and apoptosis by MTT assay and double
      staining with both annexin-V-FITC and PI, and analyzed the cross-resistance to
      various anticancer drugs. Expression of IAP compared with that in parental cells
      was evaluated by real-time quantitative PCR. RESULTS: The BGC-823 resistant
      cells, BGC-823/R1, R2 and R3 cells, were 10.2-, 24.5-, 56.3-fold more resistant
      to docetaxel than parental cells, respectively, and this resistance was
      paralleled with reduced induction of apoptosis. BGC-823/R3 cells showed cross
      resistance to paclitaxel, whereas exhibited weak or no cross-resistance against 5
      fluorouracil, cisplatin and oxaliplatin. The expressions of survivin and XIAP
      were gradually increased with the extent of docetaxel resistance (r = 0.909, P <
      0.001 and r = 0.892, P < 0.001, respectively). CONCLUSION: IAP may make an
      important contribution to the resistance to the apoptotic effect of docetaxel in
      gastric cancer, and could be used as a potential therapeutic target.

PMID- 19102933
TI  - [Inhibition of bladder cancer cell growth and angiogenesis by co-blockage of
      vascular endothelial growth factor and its receptor KDR].
AB  - OBJECTIVE: To study the effect of co-blockage of vascular endothelial growth
      factor (VEGF) and its receptor (KDR) on growth of bladder carcinoma T24 cells and
      nude mice xenograft. METHODS: T24 cell line co-transfected with VEGF siRNA and
      sKDR expression plasmids was developed and its proliferation was assayed by MTT
      and apoptosis by FCM. The nude mice model bearing bladder carcinoma xenograft was
      established. The tumor cell VEGF expression, stroma microvessel density (MVD) and
      tumor cell topoisomerase II alpha (Topo II alpha) expression were detected by
      immunohistochemistry. Cell apoptosis was estimated by TUNEL assay. RESULTS: MTT
      assay showed that cell proliferation in VEGF siRNA, sKDR and combination groups
      was 56.3% +/- 8.3%, 42.6% +/- 13.8% and 32.5% +/- 4.3%, respectively,
      significantly lower than that in the scramble control (97.3% +/- 11.6%, P <
      0.0001). FCM showed there were sub-diploid apoptotic peaks before G1 phase in
      VEGF siRNA, sKDR and combination groups, and apoptosis ratio was 5.1% +/- 0.9%,
      4.2% +/- 0.5% and 8.8% +/- 0.7%, respectively, all of which were higher than that
      in the scramble control (0.9% +/- 0.4%, P < 0.05), and the combination group had
      even more higher apoptosis than the two singlely treated groups (P < 0.01). In
      vivo test showed that tumor growth was inhibited in VEGF siRNA, sKDR and
      combination groups, and from day 16 the tumor volume in combination group was
      significantly smaller than that in scramble control (P < 0.05), and from day 28
      the tumor almost lost the ability to further growth. Immunohistochemistry
      revealed VEGF expression in combination group was 54.37 +/- 5.28, significantly
      lower than that in the scramble control (141.66 +/- 8.59, P < 0.0001). MVD number
      was only 8.22 +/- 3.79, much less compared with that in the scramble control
      (61.76 +/- 5.28, P < 0.0001) or sKDR group (19.46 +/- 4.16, P = 0.0089). Tumor
      cell proliferation index in the combination group (1.5% +/- 0.7%) was
      significantly decreased compared with that in the scramble control (11.8% +/-
      5.2%, P < 0.0001), and apoptosis index (67.2% +/- 8.5%) was much higher than that
      in the scramble control (8.7% +/- 2.7%, P < 0.0001), VEGF siRNA group (54.3% +/-
      4.8%, P = 0.0492) or sKDR group (52.3% +/- 6.4%, P = 0.0293). CONCLUSION: VEGF
      siRNA or sKDR alone can inhibit tumor cell proliferation and induce cell
      apoptosis, but co-blockage of VEGF and KDR by their combination shows more
      significant therapeutic efficacy.

PMID- 19102934
TI  - [The effect of p21 on transcription of survivin in hepatocellular carcinoma HepG2
      cells and its regulation mechanism].
AB  - OBJECTIVE: To observe the inhibitory effect of cyclin-dependent kinase inhibitor
      p21 on regulation of survivin transcription in human liver cancer HepG cells, and
      explore the related mechanisms. METHODS: Doxorubicin (DOX) was used to treat HepG
      cells. Eukaryotic vector pEGFP-C2-p21 was transfected into HepG cells by
      lipofectamine and positive clones were screened out by G418. The mRNA expression
      of p21, p53 and survivin were detected by real-time fluorescent quantitative
      polymerase chain reaction (RQ-PCR). Flow cytometry was used to determine the cell
      cycle phases, and reverse transcription polymerase chain reaction (RT-PCR) was
      used to measure the levels of E2F-1 or p300. RESULTS: After treatment with DOX,
      the expression of p53 and p21 was increased, whereas that of survivin was reduced
      during 24 hours of the treatment. After transfection the p21 level was 2100.1
      fold or 980.9-fold enhanced in comparison with that in HepG2 cells or HepG2-pEGFP
      cells. Survivin level was markedly down-regulated to 0.5% or 0.6% relative to
      that in the other two groups, nevertheless, significant p53 changes were not
      observed. Overexpression of p21 resulted in G1/G0 phase arrest (F = 31.59, P <
      0.01), meanwhile, E2F-1 mRNA or p300 mRNA were less expressed compared with that
      in the other controls (F(E2F-1) = 125.28, P < 0.05; Fp300 = 46.01, P < 0.01).
      CONCLUSION: p21 could be a potential mediator of survivin suppression at
      transcription level in HepG2 cells, which might be through the block at G1/G0
      phase and down-regulation of transcription factors E2F-1 and p300.

PMID- 19102935
TI  - [Effect of betulinic acid on proliferation and apoptosis in Jurkat cells and its
      mechanism].
AB  - OBJECTIVE: To investigate the anticancer effects of betulinic acid (BA) on Jurkat
      cells in vitro and its molecular mechanism. METHODS: The effects of betulinic
      acid on the growth of Jurkat cells were studied by 3-(4, 5-dimethyl-2-thiazolyl)
      2, 5diphenyl-2H-tetrazolium (MTT) assay. Apoptosis was assessed by Hoechst33258
      staining and annexin-V/PI double-labeled cytometry. The effect of betulinic acid
      on the cell cycle of Jurkat cells was studied by propidium iodide staining. RT
      PCR and Western blot were used to analyze the changes of cyclin D3, bcl-xl mRNA
      and protein levels in Jurkat cells after treatment with betulinic acid. RESULTS:
      The proliferation of Jurkat cells was decreased in betulinic acid-treated group
      at a 24 h IC50 value of 70.0 micromol/L. The effect of betulinic acid to induce
      apoptosis in Jurkat cells was in a time- and dose-dependent manner. Jurkat cells
      treated with betulinic acid showed an increase of G0/G1 phase and decrease of S
      phase. The Jurkat cells treated with 0, 20, 60, 100 micromol/L betulinic acid for
      24 h, showed an increased G0/G1 phase from 31.0% to 58.8%, whereas decreased S
      phase from 61.5% to 35.8%, respectively. PBMC was less sensitive to the cytotoxic
      effect of betulinic acid than Jurkat cells. The expression of cyclin D3, bcl-xl
      mRNA and protein were decreased sharply in Jurkat cells treated with betulinic
      acid. CONCLUSION: Betulinic acid can inhibit the proliferation of Jurkat cells by
      regulating the cell cycle that arrests cells at G0/G1 phase and induces apoptosis
      in Jurkat cells. The antitumor effects of betulinic acid may be related to down
      regulation of the expression of cyclin D3 and bcl-xl.

PMID- 19102936
TI  - [Down-regulation of PGC-1alpha expression in human hepatocellular carcinoma].
AB  - OBJECTIVE: To study the effect of PGC-1alpha in human liver carcinogenesis, and
      explore the regulatory role of PGC-1alpha in the development of liver cancer.
      METHODS: The changes of PGC-1alpha mRNA level in normal human liver tissues and
      human liver tumors was examined by quantitative RT-PCR. PGC-1alpha mRNA level was
      interfered by siRNA in human liver cell line L02 in vitro, and their
      morphological changes were observed by pathology with HE staining. The
      ultrastructure of cells was observed by electron microscopy. In addition, the
      gene expression pattern of decreasing PGC-1alpha in L02 cells and liver tumor
      tissue was compared by human genome 70-mer oligonucleotide microarray analysis.
      RESULTS: PGC-1alpha expression was weaker in the malignant liver tumors compared
      with that in normal liver tissues. When PGC-1alpha expression was suppressed in
      human liver L02 cells, the cells became smaller with enlarged nuclei, and myelin
      figures were observed in mitochondria by electron microscopy, similar with the
      ultrastructure of liver cancer cells. Microarray analysis showed that the
      decrease of PGC-1alpha in L02 cells induced up-regulation of some oncogenes and
      adhesive genes, and down-regulation of a number of tumor suppressor genes and
      cell proliferation suppressor genes. The changes of decreasing expression pattern
      of PGC-1alpha gene in L02 cells were similar to those in human liver cancer
      tissue. CONCLUSION: The results of the present study show that PGC-1alpha is down
      regulated in liver cancers and is involved in the malignant transformation in
      human normal liver cells in vitro, suggesting an important regulatory role of PGC
      1alpha in the development of liver cancer.

PMID- 19102937
TI  - [Expression of TFPI-2 gene in pancreatic carcinoma and its prognostic
      significance].
AB  - OBJECTIVE: To detect the expression of TFPI-2 gene in pancreatic carcinoma, and
      to evaluate its prognostic significance in patients with pancreatic carcinoma.
      METHODS: Reverse transcription polymerase chain reaction (RT-PCR) and Western
      blot were used to detect the expression of TFPI-2 mRNA and protein in the
      pancreatic carcinoma tissue samples from 41 patients. The correlation of its
      expression with clinicopathological features and its prognostic significance were
      analyzed. RESULTS: The expression of TFPI-2 mRNA and protein in moderately or
      poorly differentiated pancreatic carcinoma tissues, or in cases with nerve
      involvement, lymph node and blood vessel invasion was significantly lower than
      that in the highly differentiated one, or without nerve involvement, or neither
      lymphatic nor blood vessel invasion (P < 0.05). The median survival time of
      patients with high expression of TFPI-2 (12.0 months) was significantly longer
      than that with low expression of TFPI-2 (5.1 months, P < 0.05). The Cox model
      analysis showed that the expression of TFPI-2 was an independent marker for
      prognosis in patients with pancreatic carcinoma. CONCLUSION: The expression of
      TFPI-2 is correlated with clinical stage and differentiation of pancreatic
      carcinoma, and can be used as a prognostic marker for pancreatic carcinoma.

PMID- 19102938
TI  - [Correlation of VEGF and Ki67 expression with sensitivity to neoadjuvant
      chemoradiation in rectal adenocarcinoma].
AB  - OBJECTIVE: To investigate the correlation of expression of vascular endothelial
      growth factor (VEGF) and proliferating cell nuclear antigen (Ki67) with
      sensitivity to neoadjuvant chemoradiation in rectal adenocarcinoma. METHODS:
      Samples of pretreatment biopsies and the resected specimens after neoadjuvant
      therapy in 32 patients with rectal adenocarcinoma were collected, and the
      expression of Ki67 and VEGF were detected by immunohistochemistry using specific
      antibodies. The correlation of Ki67 and VEGF expression with clinicopathological
      factors were analyzed. RESULTS: The level of VEGF expression was significantly
      correlated with lymph node metastasis (P = 0.033), depth of tumor invasion (P =
      0.007) and TNM stage (P = 0.016), but not with histological type, tumor size, age
      and gender of the patients (P > 0.05). However, VEGF expression was found to be
      negatively and significantly correlated with the sensitivity to neoadjuvant
      chemoradiation (P = 0.016), and a transient increase of VEGF expression was
      detected in the resected specimens after neoadjuvant therapy (P = 0.035). Ki67
      labeling index (Ki67-LI) was found to be significantly correlated with lymph node
      metastasis (P = 0.028), but not with tumor size, age and gender of the patients
      (P > 0.05). It was also found that tumors with lower Ki67-LI expression were more
      sensitive to neoadjuvant therapy than that with higher expression of Ki67-LI (P =
      0.032). In contrast with VEGF, the Ki67 expression level decreased after
      neoadjuvant therapy, but no statistical significance was found between
      pretreatment and posttreatment specimens (P > 0.05). CONCLUSION: The preliminary
      results of this study demonstrate that the expression of VEGF and Ki67 in
      pretreatment biopsy of rectal adenocarcinoma may be used as a biomarker to
      predict tumor response to neoadjuvant chemoradiation.

PMID- 19102939
TI  - [Clinical significance of angiopoietin-2 expression in oral squamous cell
      carcinoma].
AB  - OBJECTIVE: To investigate the expression of angiopoietin-2 (Ang-2) and its
      clinical significance in oral squamous cell carcinoma. METHODS: The expression of
      Ang-2 mRNA was measured by real-time RT-PCR, and the expression of Ang-2 protein
      in tissue samples was detected by immunohistochemical staining. RESULTS: The mean
      dCt value of Ang-2 mRNA expression in the cancer tissue was 6.86 +/- 1.37,
      significantly lower than that in the paired adjacent non-cancerous tissue (7.95
      +/- 2.08, P < 0.05), indicating a significantly higher expression of Ang-2 mRNA
      in the cancerous tissue than that in the adjacent non-cancerous tissue. The
      distribution of Ang-2 protein was found not only in the vascular endothelial
      cells but also in tumor cells. Semi-quantitative analysis revealed that the
      expression of Ang-2 protein in tumor specimens (53.6%) was significantly higher
      than that (24.0%) in the paired adjacent non-cancerous tissue (P < 0.05), the
      result was well consistent with that measured by RT-PCR. The dCt value of Ang-2
      mRNA expression was 6.48 +/- 1.16 in the patients with metastasis in lymph nodes
      versus 7.16 +/- 1.49 in those without, with a non-significant difference between
      the two groups (P > 0.05). As regards the clinical stages, no significant
      difference was found between the expressions of Ang-2 mRNA in stage I + II (7.11
      +/- 1.63) and stage III + IV cases (6.49 +/- 1.10, P > 0.05). CONCLUSION:
      Angiopoietin-2 protein is expressed not only in vascular endothelial cells, but
      also in tumor cells, suggesting that angiopoietin-2 may take part in angiogenesis
      in oral squamous cell carcinoma. However, our results that high expression of
      angiopoietin-2 mRNA is not correlated with lymph node metastasis and clinical
      stages, needs to be further verified in a large scale study.

PMID- 19102940
TI  - [Expression of CK5/6 and CK17 and its correlation with prognosis of triple
      negative breast cancer patients].
AB  - OBJECTIVE: To investigate the correlation of CK5/6 and CK17 expression with
      clinical outcome in patients with triple-negative [ER(-), PR(-), Her-2(-)] breast
      cancer. METHODS: 112 patients with breast cancer treated by surgery between 2000
      and 2002 were included in this study. All cases were immunohistochemically proven
      to be triple-negative. Samples of formalin-fixed and paraffin-embedded surgical
      specimens were obtained for immunohistological examination for CK5/6 and CK17
      expression. The correlation of the gene expression with clinicopathological
      features and outcome of the patients was analyzed. RESULTS: Of the 112 triple
      negative patients, five-year disease-free survival rate was 73.2% (82/112). The
      positive rate of both CK5/6 and CK17 was 21.4% (24/112), either CK5/6 or CK17
      positive was 46.4% (52/112). It was shown by Kaplan-Meier curve that positive
      CK5/6, CK17 or CKs (CK5/6 or CK17 positive) was correlated with poor five-year
      disease-free survival (P = 0.020, P = 0.032, P = 0.003); and positive staining of
      CK5/6 or CKs was correlated with poor five-year overall survival (P = 0.027, P =
      0.015). Of the 91 patients with invasive ductal carcinoma, a correlation of CK5/6
      or CK17 positive staining with high grade differentiation was observed (P =
      0.030), and with axillary lymph node metastasis was also noticed (P = 0.044).
      Multivariate analysis by Cox regression showed that differentiation grade,
      pathological stage and expression of CK5/6 were factors affecting both the
      disease-free-survival and overall-survival, while menopausal status was an
      independent factor affecting the disease-free-survival. CONCLUSION: Positive
      expression of CK5/6 or CK17 in patients with triple-negative breast cancer is
      correlated with poor prognosis, high grade differentiation and axillary lymph
      node metastasis.

PMID- 19102941
TI  - [The correlation between serum osteocalcin and parathyroid hormone levels in
      cancer patients and bone metastasis].

PMID- 19102942
TI  - [Application of protein markers in combination with ThinPrep bronchial brush
      cytology in classification of lung cancer subtypes].
AB  - OBJECTIVE: To evaluate the value of application of cellular protein markers
      stained by immunocytochemistry in combination with ThinPrep bronchial brush
      cytology in classification of lung cancer subtypes. METHODS: Remaining bronchial
      brush cytology samples from 206 lung cancer patients with positive cytological
      diagnosis and 45 fine needle aspiration samples of resected lung carcinomas were
      collected. The expressions of CK10/13, CK7, CK18, CD56 and SYN in those samples
      were detected by immunocytochemistry (ICC) using corresponding antibodies.
      RESULTS: The sensitivity and specificity of CK10/13 were 94.7% and 72.0%,
      respectively, in diagnosis of squamous cell carcinoma. The sensitivity and
      specificity of CK7 were 98.6% and 61.5%, and those of CK18 were 98.6% and 37.5%,
      respectively, in diagnosis of adenocarcinoma. The sensitivity and specificity of
      CD56 were 86.3% and 82.9%, and those of SYN were 81.6% and 93.5%, respectively,
      in diagnosis of small cell lung cancer. No significant difference was found in
      the expressions of CK10/13, CK7 and CK18 protein markers among differently
      differentiated lung squamous cell carcinomas and adenocarcinomas (P > 0.05). The
      classification rate of cytology in combination with ICC in differential diagnosis
      for 44 cases of unclassified lung cancer reached 90.0% for squamous cell
      carcinoma, 96.3% for adenocarcinoma, and 100.0% for small cell lung carcinoma.
      CONCLUSION: Application of cellular protein markers in combination with ThinPrep
      bronchial brush cytology is helpful to improve the differential diagnosis of lung
      cancer subtypes, and may become a supplementary diagnostic method in
      subclassification of lung cancer.

PMID- 19102943
TI  - [Selective exclusion of hepatic outflow and inflow in hepatectomy for huge
      hepatic tumor].
AB  - OBJECTIVE: To evaluate the effects of selective hepatic vascular exclusion (SHVE)
      on prevention of serious hemorrhage and air embolism during hepatectomy and on
      the liver function after operation. METHODS: From January 2004 to March 2007, 29
      huge hepatic tumors were resected in our department. Both SHVE and Pringle
      maneuver were used to control the blood loss during hepatectomy. They were
      divided into two groups: SHVE group (15 cases) and Pringle group (14 cases). Data
      regarding the intraoperative and postoperative courses of the patients were
      analyzed. RESULTS: There was no significant difference between the two groups
      regarding the age, sex, tumor size, cirrhosis, HbsAg positive rate and operating
      time (P > 0.05). Intraoperative blood loss was reduced significantly in the SHVE
      group (P < 0.05). The serum prealbumin levels on the postoperative day 1, 3 and 7
      in SHVE group were significantly higher than those in the Pringle group (P <
      0.05). The serum ALT value in SHVE group was significantly lower than that in the
      Pringle group on postoperative day 1, 3 and 7. The mean drainage volume in SHVE
      group was significantly less than that in the Pringle group on postoperative day
      1 and 2. Liver failure occurred in two cases of the Pringle group, while no one
      in the SHVE group. Rupture of hepatic vein with massive blood loss occurred in 3
      cases and air embolism in one case of the Pringle group, but did not occur in any
      case of the SHVE group. CONCLUSION: When the selective exclusion of hepatic
      outflow and inflow is applied in hepatectomy, the resection rate of huge hepatic
      tumors and operative tolerance of hepatectomy are improved. It is a safe and
      rational operation type, and provides an optimal choice for hepatectomy.

PMID- 19102944
TI  - [Value of recombinant human thrombopoietin in the treatment of chemotherapy
      induced thrombocytopenia in patients with solid tumor].
AB  - OBJECTIVE: To evaluate the efficacy and safety of domestically manufactured
      recombinant human thrombopoietin (rhTPO) in the treatment for chemotherapy
      induced thrombocytopenia in patients with solid tumors. METHODS: A non-randomized
      controlled study was conducted. Seventy-two patients with platelet count < 75 x
      10(9)/L after chemotherapy were enrolled into this study according to the
      standard criteria of NCI-CTC toxicity stratification. Thirty-five patients in the
      treatment-group received subcutaneous injection of rhTPO at a dose of 15,000 U/d,
      another 37 patients in the control group received subcutaneous injection of rhIL
      11a at a dose of 3 mg/d as the paralleled control. RESULTS: The mean minimal
      platelet count after rhTPO treatment was (46.2 +/- 20.3) x 10(9)/L in the
      treatment-group versus (37.2 +/- 16.7) x 10(9)/L in the control-group (P < 0.05),
      while the mean maximal platelet count was (250.2 +/- 159.0) x 10(9)/L versus
      (160.5 +/- 96.4) x 10(9)/L (P < 0.05). The incidence rate of adverse effects and
      duration of grade III and IV thrombocytopenia in the treatment-group was also
      significantly lower than those in the control-group. Furthermore, the patients
      receiving platelet transfusion were 4/35 in the treatment-group versus 11/37 in
      the control-group (P > 0.05). The side-effect rate in the treatment-group was
      significantly lower than that in the control-group (11.4% versus 78.4%, P <
      0.01). CONCLUSION: Compared with rhIL-11, administration of rhTPO after
      chemotherapy is safe and effective with mild adverse effects in reducing the
      degree and duration of thrombocytopenia.

PMID- 19102945
TI  - [Long-term outcome of testicular seminoma in 294 patients].
AB  - OBJECTIVE: To analyze the correlation of long-term survival with the treatment
      strategies in patients with testicular seminoma. METHODS: Clinical data of 294
      patients with testicular seminoma treated in our hospital between 1959 and 2004
      were collected and analyzed. The median age of the patients was 37 years (range
      13 - 70 years). Among them, 260 were in stage I disease, 16 in stage II, and 18
      in stage III. The patients were treated by surgical resection plus chemotherapy
      and/or radiotherapy. The survival rate was calculated using Kaplan-Meier method
      and log-rank test using SPSS 13.0 software. RESULTS: The overall 5-, 10-, 20- and
      30-year survival rates in this series were 92.1%, 91.8%, 85.5% and 71.4%,
      respectively. The major prognostic factor was found to be clinical stage. The
      patients with adjuvant chemotherapy after orchiectomy had better 10-year survival
      than the patients without (97.5% vs. 79.2%, P = 0.001). For stage II/III
      patients, the patients with chemotherapy and the patients with chemotherapy plus
      radiotherapy had a similar progression-free survival (PFS) and overall survival
      (OS) (P > 0.05). CONCLUSION: Testicular seminoma is sensitive to chemotherapy and
      radiotherapy, and a good cure rate can still be achieved in the relapsed patients
      with a salvage treatment. Therefore, wide excision and long-term chemotherapy
      should be avoided in order to maintain the quality of life in those patients.

PMID- 19102946
TI  - [Combined-modality therapy for 150 cases of early-stage Hodgkin's lymphoma].
AB  - OBJECTIVE: To compare the efficacy of chemotherapy alone, radiotherapy alone and
      combined-modality therapy in the treatment for early-stage Hodgkin's lymphoma
      (HL). METHODS: From 1999 to 2002, totally 150 patients with stage I or II HL were
      treated in our hospital. They were stratified into several groups based on
      initial treatment strategy: chemotherapy alone (CT group, n = 22), radiotherapy
      alone (RT group, n = 18), combined-modality therapy (CMT group, n = 109) and
      surgical resection (SR group, n = 1). Chemotherapy regimens were mainly ABVD
      (adriamycin, bleomycin, vinblastine and dacarbazine) and MOPP (mechlorethamine,
      vincristine, procarbazine and prednisone). Radiotherapy modes included involved
      field radiotherapy (IFRT), extended field radiotherapy (EFRT) and sub-total nodal
      irradiation (STNI). RESULTS: The pathological types included nodular sclerosis
      (NS, n = 84), mixed-cellularity (MC, n = 39), lymphocyte-predominant (LP, n =
      23), lymphocyte-depleted (LD, n = 3) and nodular lymphocyte predominant Hodgkin's
      disease (NLPHD, n = 1). Of those, 72 were evaluble in terms of prognostic
      factors. No poor prognostic factor was found in 36.1% or 29.2% of the patients
      according to EORTC or GHSG criteria, respectively. There were 33 patients with
      complete response (CR), 109 with partial response (PR), 5 with stable disease
      (SD) and 3 with progressive disease (PD) after initial therapy. The median follow
      up period was 71.5 months. The overall 7-yr survival rate was 89.3%, and
      treatment failure rate at 6 years was 18.8%. The response rate of CMT group was
      superior to that of CT group, and the patients with nodular sclerosis or mixed
      cellularity type had significantly lower risk of treatment failure (P = 0.009 and
      0.019, respectively). The multivariate analysis revealed that the treatment
      strategies affected the prognosis significantly. The risk of failure of
      chemotherapy alone was 2.52 times higher than that of combined-modality therapy
      (P = 0.004). No predictive factor affecting OS was identified by either
      univariate or multivariate analysis. The patients in CMT group suffered more
      adverse effects than those in either CT or RT groups, which mainly consisted of
      leucopenia, alopecia and gastrointestinal symptoms. CONCLUSION: Combined-modality
      therapy is more effective than chemotherapy alone or radiotherapy alone in the
      treatment for early stage Hodgkin's lymphoma. Though its acute adverse effects
      are more severe than that of chemotherapy or radiotherapy alone, it may reduce
      the risk of treatment failure.

PMID- 19102947
TI  - [The present understanding of medicinal treatment of stomach cancer].

PMID- 19102950
TI  - Gender-specific issues in the management of patients with acute coronary
      syndrome.

PMID- 19102951
TI  - Gender differences in efficacy of primary percutaneous coronary intervention in
      patients with ST-elevation myocardial infarction.
AB  - BACKGROUND: The clinical outcome of percutaneous coronary intervention (PCI) is
      poorer in women than that in men. This study aimed at comparing the impact of
      gender difference on the strategy of primary PCI in patients with acute ST
      segment elevation myocardial infarction (STEMI). METHODS: Two hundred and fifty
      nine patients with STEMI who underwent primary PCI within 12 hours of symptom
      onset were enrolled. The male group consisted of 143 men aged > 55 years, and a
      female group included 116 women without age limitation. Procedural success was
      defined as residual stenosis < 20% with thrombolysis in myocardial infarction
      flow grade > 2 and without death, emergency bypass surgery or disabling cerebral
      events during the hospitalization. The rate of major adverse cardiac events
      (MACE), including death, nonfatal myocardial infarction and target vessel
      revascularization during follow-up, was recorded. RESULTS: Female patients were
      more hypertensive and diabetic and with fewer cigarette smokers than male
      counterparts. The prevalence of angiographic 3-vessel disease was higher in the
      female group, but the procedural success rate was comparable between the two
      groups (94.4% vs 92.2%). The occurrence rate of MACE did not differ during the
      hospitalization (4.2% vs 6.0%, P = 0.50), but was significantly higher in the
      female group during follow-up (mean (16.0 +/- 11.2) months) than that in the male
      group (5.4% vs 0.7%, P = 0.02). CONCLUSION: Despite a similar success rate of
      primary PCI and in-hospital outcomes in both genders, female patients with acute
      STEMI still have a worse prognosis during the long-term follow-up.

PMID- 19102952
TI  - Impact of admission creatinine level on clinical outcomes of patients with acute
      ST-elevation myocardial infarction undergoing primary percutaneous coronary
      intervention with drug-eluting stent implantation.
AB  - BACKGROUND: Prognosis of patients with acute ST-elevation myocardial infarction
      (STEMI) and renal dysfunction (RD) who received primary percutaneous coronary
      intervention (PCI) has not been fully investigated in the drug-eluting stent
      (DES) era. This study aimed to evaluate the impact of admission serum creatinine
      level on short-term outcomes in patients with acute STEMI undergoing DES-based
      primary PCI. METHODS: Primary PCI with DES implantation was attempted in 619
      consecutive STEMI patients within 12 hours of symptom onset. Among them, 86
      patients had a serum creatinine level > or = 115 micromol/L on admission (RD
      group), and the remaining 533 patients had normal renal function (non-RD group).
      The primary endpoint was 30-day major adverse cardiac events (MACE, including
      death, non-fatal reinfarction, and target vessel revascularization), and the
      secondary endpoint was subacute stent thrombosis. RESULTS: Patients in the RD
      group were older than those in the non-RD group. There are more female patients
      in the RD group and they had a history of hypertension, myocardial infarction and
      revascularization. The occurrence rates of Killip class > or = 2 (29.1% vs 18.6%,
      P = 0.02) and multi-vessel (62.8% vs 44.5%, P = 0.001) and triple vessel disease
      (32.6% vs 18.2%, P = 0.002), in-hospital mortality (9.3% vs 3.8%, P = 0.03), and
      MACE rate during hospitalization (17.4% vs 7.7%, P = 0.006) were higher in the RD
      group than those in the non-RD group. At a 30-day clinical follow-up, the MACE
      free survival rate was significantly reduced in the RD group (76.7% vs 89.9%, P =
      0.0003). Angiographic stent thrombosis occurred in 3 (3.5%) and 7 (1.3%) of
      patients in the RD group and non-RD group, respectively (P = 0.15). Multivariate
      analysis revealed that the serum creatinine level > or = 115 micromol/L on
      admission was an independent predictor for MACE rate at a 30-day follow-up
      (Hazard ratio (HR) 3.31, 95% CI 1.19 - 9.18, P < 0.001). CONCLUSION: Despite
      similar prevalence of stent thrombosis at a 30-day clinical follow-up, the short
      term prognosis of STEMI patients with elevated serum creatinine on admission
      undergoing DES-based primary PCI remains unfavorable.

PMID- 19102953
TI  - Comparative effects of percutaneous coronary intervention for infarct-related
      artery only or for both infarct- and non-infarct-related arteries in patients
      with ST-elevation myocardial infarction and multi-vessel disease.
AB  - BACKGROUND: Rapid recanalization of infarct-related artery (IRA) has become the
      major target during primary percutaneous coronary intervention (PCI) for patients
      with ST-elevation myocardial infarction (MI), but strategy for treatment of non
      IRA lesions in this setting remains unclear. This study aimed to compare long
      term effects between PCI for IRA only and that for both IRA and non-IRA in ST
      elevation MI patients with multi-vessel disease. METHODS: A total of 242 eligible
      patients with ST-elevation MI and at least two diseased coronary arteries
      (luminal narrowing > or = 70%) undergoing primary PCI were included. Of them, 149
      patients underwent primary PCI for IRA only (group 1), and 93 received primary
      PCI for IRA followed by elective PCI for non-IRA 7 to 15 days after acute
      myocardial infarction (AMI) (group 2). Drug-eluting stents (DESs) were deployed
      in more than 90% of the patients. RESULTS: The two groups did not differ with
      respect to baseline clinical and angiographic characteristics. No significant
      differences were observed in 12-month clinical follow-up results regarding major
      adverse cardiac events (11.5% vs 15.1%, P > 0.05) and target lesion
      revascularization (8.1% vs 7.6%, P > 0.05) between the two groups. However,
      patients in group 1 had higher rates of recurrent angina (10.1% vs 2.1%, P <
      0.05) and depressed left ventricular ejection fraction evaluated by
      echocardiography (0.56 +/- 0.22 vs 0.63 +/- 0.25, P < 0.05). CONCLUSION: With the
      use of DESs, complete revascularization with elective PCI for non-IRA after
      primary PCI may exert a beneficial effect on long-term symptomatology and left
      ventricular function in patients with ST-elevation MI and multi-vessel disease.

PMID- 19102954
TI  - Clinical profile and outcomes of atrial fibrillation in elderly patients with
      acute myocardial infarction.
AB  - BACKGROUND: Atrial fibrillation (AF) occurs commonly in patients with acute
      myocardial infarction (MI) and is associated with an increased long-term
      mortality. This study aimed to investigate the clinical characteristics and
      outcomes of AF in in-hospital elderly Chinese patients with acute MI. METHODS: A
      total of 967 patients with acute MI, aged >/= 65 years, were categorized on the
      basis of the absence or presence of AF. Patients with documented AF were
      classified into two subgroups: the ongoing AF group and the new-onset AF group.
      We retrospectively evaluated the clinical profile, in-hospital outcomes, and
      effects of revascularization on the incidence of AF in elderly patients with
      acute MI. RESULTS: AF was documented in 100 (11.53%) patients and the incidence
      of new-onset AF was 6.51% during hospitalization. History of old MI and
      cerebrovascular events were more common in patients with AF than in those without
      AF (P < 0.001, P < 0.01, respectively). The incidence of AF was higher in
      patients with non-ST elevated MI (P = 0.014), inferior wall MI (P = 0.004) and
      cardiac function of Killip class III or IV (P = 0.008). Patients with AF had more
      complication of pneumonia (P = 0.003) and longer hospital stay. Left circumflex
      coronary artery involvement was more common in patients with AF (compared with
      patients without AF, P < 0.001). Percutaneous coronary intervention or coronary
      artery bypass grafting significantly decreased the incidence of new-onset AF from
      7.97% to 3.82% (P = 0.017). AF depended to heart failure, increased the in
      hospital mortality. CONCLUSIONS: AF is common in elderly patients with acute MI
      and is associated with poorer clinical outcomes. Revascularization reduces the
      incidence of AF and thus improves the clinical outcomes in these patients.

PMID- 19102955
TI  - Clinical and angiographic characteristics of premenopausal women with coronary
      artery disease.
AB  - BACKGROUND: Coronary artery disease (CAD) is generally considered as a disease of
      middle-aged men. It is widely accepted that the risk for CAD of premenopausal
      women is low because of hormone protection. Based on our clinical experience,
      more and more premenopausal women suffer from angina and myocardial infarction
      without adequate concern. Even now, there are still limited detailed data to
      describe the characteristics, mechanism and prognosis of premenopausal CAD
      patients. This article aimed to analyze the clinical and angiographic
      characteristics of premenopausal women with CAD. METHODS: A total of 565
      premenopausal women and 721 postmenopausal women (56 - 60 years old) who
      underwent coronary angiography for the first time from April 2004 to December
      2007 were enrolled. The clinical data and coronary angiographic characteristics
      (presence, localization, length and severity) were compared between the
      premenopausal and postmenopausal CAD groups. RESULTS: Premenopausal CAD patients
      presented less frequently with hypertension, diabetes mellitus and dyslipidemia
      compared with postmenopausal CAD patients (55.0% vs 66.0%, 15.0% vs 31.5%, 23.9%
      vs 37.4%, respectively; all P < 0.05). Although we found more frequent
      involvement of single vessel in premenopausal CAD (43.2% vs 26.9%, P = 0), and
      triple vessels in postmenopausal (56 - 60 years old) CAD patients (33.8% vs
      20.4%, P = 0), much more severe lesions (> or = 90%) at left main (2.9% vs 1.1%,
      P = 0.048) and proximal left anterior descending artery (LAD) (28.2% vs 16.6%, P
      = 0) in the premenopausal CAD group were found. CONCLUSION: Premenopausal women
      with chest discomfort are always found to have obvious atherosclerosis, more
      inclined to be located at the left main and proximal LAD, which is a strong
      predictor of an adverse clinical outcome.

PMID- 19102956
TI  - Is the use of cardiopulmonary bypass for isolated coronary artery bypass an
      independent predictor of mortality and morbidity in patients with severe left
      ventricular dysfunction?
AB  - BACKGROUND: Patients presenting with severe left ventricular dysfunction (SLVD)
      undergoing conventional coronary artery bypass grafting (CCABG) are at an
      increased risk of perioperative mortality and morbidity. The aim of this study
      was to assess the risk factors responsible for mortality and morbidity among
      patients with SLVD by comparing CCABG and off-pump coronary artery bypass surgery
      (OPCAB). METHODS: We retrospectively evaluated 186 consecutive patients with SLVD
      who underwent coronary artery bypass grafting (CABG), including 102 by CCABG and
      84 by OPCAB. Registry database, medical notes, and charts were studied for
      preoperative and postoperative data of the patients. Different variables and risk
      factors (preoperative, intraoperative, and postoperative) were evaluated and
      compared. The morbidity and mortality outcomes were compared in the two groups.
      The follow-up results and quality of life were assessed after surgery. RESULTS:
      The two groups had similar percentage of patients with preoperative high-risk
      profiles and no significant differences were found between groups in baseline
      variables such as age or comorbidities. There was a significant difference in the
      number of grafts used between the two groups. CCABG patients received (3.6 +/-
      0.5) grafts per patient, while OPCAB patients had (2.7 +/- 0.6) grafts (P <
      0.05). Completeness of revascularization was also significantly different between
      the two groups (CCABG 91.1% vs OPCAB 73.8%, P < 0.05). The hospital mortality was
      similar in the two groups (4.8% in OPCAB vs 5.9% in CCABG). The risk-adjusted
      mortality, according to the calculated propensity score, did not reach
      statistical significance in the two groups. In this study, OPCAB seemed to have a
      beneficial effect on reducing reoperation for bleeding, blood transfusion
      requirement, and the length of stay at ICU. But the incidence of perioperative
      myocardial infarction was more common in the off-pump group (P < 0.05). The
      degree of improvement in angina and quality of life did not differ significantly
      between the two groups. CONCLUSIONS: Using cardiopulmonary bypass is not an
      independent predictor of mortality and morbidity in patients with SLVD. Isolated
      CABG can be safely performed in SLVD patients with acceptable postoperative
      morbidity and mortality in addition to encouraging home discharge rates and
      higher quality of life. Therefore, CCABG remains a viable option in selected
      patients with SLVD.

PMID- 19102957
TI  - Mechanisms of improvement of left ventricle remodeling by trans-planting two
      kinds of autologous bone marrow stem cells in pigs.
AB  - BACKGROUND: The necrosis of a large number of myocardial cells after acute
      myocardial infarction (AMI) results in a decrease of cardiac function and
      ventricle remodeling. Stem cell transplantation could improve cardiac function
      after AMI, but the involving mechanisms have not been completely understood. The
      present study aimed to investigate the effects of transplantation of autologous
      bone marrow mononuclear cells (BM-MNC) and mesenchymal stem cells (MSCs) via the
      coronary artery on the ventricle remodeling after AMI as well as the mechanisms
      of the effects of transplantation of different stem cells on ventricle
      remodeling. METHODS: A total of 36 male pigs were enrolled in this study, which
      were divided into 4 groups: control group, simple infarct model group, BM-MNC
      transplantation group, and MSCs transplantation group. At 90 minutes when a
      miniature porcine model with AMI was established, transplantation of autologous
      BM-MNC ((4.7 +/- 1.7) x 10(7)) and MSCs ((6.2 +/- 1.6) x 10(5)) was performed in
      the coronary artery via a catheter. Ultrasound, electron microscope,
      immunohistochemical examination and real time reverse transcriptase-polymerase
      chain reaction were used respectively to observe cardiac functions, counts of
      blood vessels of cardiac muscle, cardiac muscle nuclear factor (NF)-kappaB,
      myocardial cell apoptosis, and the expression of the mRNA of vascular endothelial
      growth factor (VEGF) and basic fibroblast growth factor (bFGF) in cardiac
      muscles. Multivariate Logistic regression was used to analyze the correlation
      factors of left ventricular end-diastolic diameter (EDD). RESULTS: The number of
      blood vessels in the infarct zone and around its border in the BM-MNC
      transplantation group was more than those in the infarct model group and MSCs
      group (P = 0.0001) and there was less myocardial cell apoptosis in the stem cell
      transplantation group than that in the infarct model group (all P < 0.01). The
      positive rate of NF-kappaB in the stem cell transplantation group was lower than
      that in the infarct model group (P = 0.001). The gene expression of VEGF in the
      infarct border zone of the BM-MNC group was higher than that in the MSCs group (P
      = 0.0001). The gene expression of bFGF in the infarct border zone in the MSCs
      transplantation group was higher than that in the infarct model group and the BM
      MNC group (P = 0.0001). Left ventricular ejection fraction was inversely
      proportional to the apoptotic rate of myocardial cells and cardiac muscle NF
      kappaB but positively correlated with the number of blood vessels and the
      expression of VEGF and bFGF in the infarct zone and infarct border zone. The
      Multivariate Logistic regression analysis on the factors influencing the left
      ventricular end-diastolic diameter after stem cell transplantation showed that
      the expression of VEGF mRNA in the cardiac muscles in the infarct zone, the
      number of apoptotic myocardial cells and the expression of NF-kappaB in the
      infarct border zone were independent factors for predicting the inhibitory effect
      on the dilation of left ventricular EDD after stem cell transplantation.
      CONCLUSIONS: Transplantation of autologous BM-MNC and MSCs in pigs can improve
      the condition of left ventricular remodeling and recover the cardiac functions
      after AMI. The improvement of cardiac functions is related to the increase of
      blood vessels, the increased expression of VEGF and bFGF, the reduction of
      myocardial cell apoptosis, and the decrease of NF-kappaB level in cardiac muscle
      tissues after stem cell transplantation.

PMID- 19102958
TI  - CT guided 125iodine seed implantation for portal vein tumor thrombus in primary
      hepatocellular carcinoma.
AB  - BACKGROUND: This study evaluated the clinical application of CT guided 125iodine
      implantation in patients with portal vein tumor thrombus in primary
      hepatocellular carcinoma. METHODS: The ten patients (9 males and 1 female, aged
      from 36 to 72 years) with portal vein tumor thrombus accompanying hepatocellular
      carcinoma had been treated with comprehensive therapy including surgery,
      transcatheter arterial chemoembolization, radiotherapy ablation, microwave
      ablation or percutaneous ethanol injection. The average diameter of each tumor
      thrombus was 21.5 mm x 30.5 mm. Seeds of 30 MBq 125I were implanted 5 mm apart
      within the portal vein tumor thrombus. The follow-up after 4 months included
      enhanced spiral CT. RESULTS: CT screening of the tumours indicated that 4 out of
      10 patients showed complete response to the therapy, 5 partial response and 1
      stable disease. Adverse effects included aggravated abdominal dropsy and
      temporarily increased transaminase, which were controlled by medical management.
      Severe complications such as haemorrhage, biliary fistula, hepatic abscess,
      pancreatic fistula and hepatic function failure were not observed. Implanted
      seeds migrated to lung and left hepatic lobe in 1 case. CONCLUSION: CT guided
      implantation of 125iodine seeds, can effectively treat portal vein tumor thrombus
      accompanying hepatocellular carcinoma with minimal damage and few complications.

PMID- 19102960
TI  - Lipid signal in evaluation of intracranial meningiomas.
AB  - BACKGROUND: Using magnetic resonance imaging, diagnosis of malignant meningioma
      from benign meningioma with atypical features is uncertain. We evaluated the
      value of lipid signal in differentiating intracranial meningiomas. METHODS: 1H
      magnetic resonance spectroscopy (MRS) using a point resolved spectroscopy (TR/TE
      1000/144 ms) sequences were performed on 34 patients on a 3.0 T scanner. Lipid
      peak located at 1.3 ppm was evaluated. MRS data from these tumours were compared
      with histopathological findings (including hematoxylin and eosin staining and KP
      1 staining). RESULTS: Twenty-nine meningiomas were histologically benign (eleven
      meningothelial, thirteen fibrous, four transitional and one microcystic), three
      were atypical, and two were anaplastic. Lipid signal was detected in ten cases:
      two anaplastic, three atypical, two fibrous and three meningothelial meningiomas.
      All voxels with lipid peak in the spectrum from the tumour were evaluated. With
      creatinine peak in the normal white matter chosen as internal standard,
      lipid/creatinine ratios of anaplastic, atypical and benign meningiomas were 0.844
      +/- 0.027 (range from 0.725 to 0.994), 0.465 +/- 0.023 (range from 0.239 to
      0.724), and 0.373 +/- 0.016 (range from 0.172 to 0.571) respectively. Highly
      significant differences were noted between anaplastic and the other two subtypes.
      Patchy necrosis was observed in anaplastic meningioma, while focal necrosis was
      noted in atypical meningioma with HE stain. However, no necrosis was found in
      benign group. KP-1 stain demonstrated histocytes containing lipids in the
      necrotic region of anaplastic and atypical meningioma. CONCLUSION: The lipid
      signal at 1.3 ppm is a useful marker in evaluating the malignancy of intracranial
      meningiomas, especially in the differential diagnosis of anaplastic meningioma.

PMID- 19102961
TI  - A new modification of transanal Swenson pull-through procedure for Hirschsprung's
      disease.
AB  - BACKGROUND: The one-stage pull-through procedures for Hirschsprung's disease (HD)
      have become popular because it is well accepted by surgeons and mothers with no
      visible scar and a short hospital stay. It represents the latest development in
      the concept of a minimally invasive surgery for HD. We introduce a new method of
      transanal one-stage pull-through for Hirschsprung's disease, different from the
      transanal Soave procedure. METHODS: One hundred and thirty-four patients aged 9
      days to 5 years underwent a transanal one-stage pull-through procedure. The
      diagnosis was definite by barium enema or rectal biopsies preoperatively. The
      patients were anesthetized and placed in the lithotomy position. A urinary
      catheter was optional. Giving anorectal dilatations for half a minute, a pull
      through of the rectum above the peritoneal reflection and into the
      intussusception was performed. Fine silk suturing was performed circumferentially
      at the level of that point which was used for traction for the distal end.
      Another circumferential suture was performed parallel 0.5 cm distance above the
      original one and used for traction for the proximal intestines. The full
      thickness rectal wall was truncated between the above two circumferential sutures
      with cautery. The proximal intestines were pulled down and the mesenteric vessels
      were dissected with ligation until normal intestines were accessed; the presence
      of ganglion cells was determined by intraoperative rapid frozen section. The
      distal end was dissected anteriorly 2.5- 3.5 cm above the dentate line. The
      posterior rectal wall was split longitudinally and dissected to a point 0.5- 1.0
      cm above the dentate line. The segment of the lesion was resected. The length of
      bowel resected ranged from 12 to 50 cm (median 16.5 cm). An oblique anastomosis
      was made. RESULTS: The mean operating time was 70 minutes. Postoperative rectal
      dilation was not required. The patient tolerated feeding on the first
      postoperative day. Eighty-eight patients were followed-up. All these patients had
      2- 3 bowel movements per day at postoperative month 1. They were discharged
      within 4.5 days after the operation. Six patients presented with complications.
      All recovered by reoperation or conservative treatments. CONCLUSION: The
      modification of the transanal Swenson pull-through procedure for Hirschsprung's
      Disease is an easy adaptation to a well-established technique and has a
      reasonable result.

PMID- 19102962
TI  - Reconstruction of large limb bone defects with a double-barrel free vascularized
      fibular graft.
AB  - BACKGROUND: The use of a free, vascularized fibular graft is an important
      technique for the reconstruction of large defects in long bones. The technique
      has many advantages in strong, tubular bones; a more reliable vascular anatomy
      with a large vascular diameter and long pedicle is used, minimizing donor-site
      morbidity. Due to limitations in both fibular anatomy and mechanics, they cannot
      effectively be used to treat large limb bone defects due to their volume and
      strength. METHODS: From 1990 to 2001, 16 clinical cases of large bone defects
      were treated using vascularized double-barrel fibular grafts. Patients were
      evaluated for an average of 10 months after surgery. RESULTS: All the patients
      achieved bony union; the average bone union took 10 months post surgery, and no
      stress fractures occurred. Compared with single fibular grafts, the vascularized
      double-barrel fibular grafts greatly facilitate bony union and are associated
      with fewer complications, suggesting that the vascularized double-barrel fibular
      graft is a valuable procedure for the correction of large bone defects in large,
      long bones in addition to enhancing bone intensity. CONCLUSIONS: The vascularized
      double-barrel fibular graft is superior to the single fibular graft in
      stimulating osteogenous activity and biological mechanics for the correction of
      very large bone defects in large, long bones. Free vascularized folded double
      barrel fibular grafts can not only fill up large bone defects, but also improve
      the intensity margin. Therefore, this study also widens its application and
      enlarges the treatment targets. However, in the case of bone deformability,
      special attention should be paid to bone fixation and protection of donor and
      recipient sites.

PMID- 19102963
TI  - Auditory pre-attentive processing of Chinese tones.
AB  - BACKGROUND: Chinese tones are considered important in Chinese discrimination.
      However, the relevant reports on auditory central mechanisms concerning Chinese
      tones are limited. In this study, mismatch negativity (MMN), one of the event
      related potentials (ERP), was used to investigate pre-attentive processing of
      Chinese tones, and the differences between the function of oddball MMN and that
      of control MMN are discussed. METHODS: Ten subjects (six men and four women) with
      normal hearing participated in the study. A sequence was presented to these
      subjects through a loudspeaker, the sequence included four blocks, a control
      block and three oddball blocks. The control block was made up of five components
      (one pure tone and four Chinese tones) with equiprobability. The oddball blocks
      were made up of two components, one was a standard stimulus (tone 1) and the
      other was a deviant stimulus (tone 2 or tone 3 or tone 4). Electroencephalogram
      (EEG) data were recorded when the sequence was presented and MMNs were obtained
      from the analysis of the EEG data. RESULTS: Two kinds of MMNs were obtained,
      oddball MMN and control MMN. Oddball MMN was obtained by subtracting the ERP
      elicited by standard stimulation (tone 1) from that elicited by deviant
      stimulation (tone 2 or tone 3 or tone 4) in the oddball block; control MMN was
      obtained by subtracting the ERP elicited by the tone in control block, which was
      the same tone as the deviant stimulation in the oddball block, from the ERP
      elicited by deviant stimulation (tone 2 or tone 3 or tone 4) in the oddball
      block. There were two negative waves in oddball MMN, one appeared around 150 ms
      (oddball MMN 1), the other around 300 ms (oddball MMN 2). Only one negative wave
      appeared around 300 ms in control MMN, which was corresponding to the oddball MMN
      2. We performed the statistical analyses in each paradigm for latencies and
      amplitudes for oddball MMN 2 in discriminating the three Chinese tones and
      reported no significant differences. But the latencies and amplitudes for control
      MMN in discriminating the three tones all were significantly different.
      CONCLUSIONS: There are evident waveforms for oddball and control MMN obtained in
      normal hearing persons, indicating that the change of Chinese tones could be
      detected in the pre-attentive stage. Because control MMN can eliminate reflects
      for physical characteristics of sound, it is the genuine memory-based pre
      attentive processing. Since control MMN can reflect the differences of Chinese
      tones processing better than oddball MMN, it is more sensitive in evaluating pre
      attentive processing in Chinese tones discrimination.

PMID- 19102965
TI  - Hyperphosphatemia-induced hyperparathyroidism in 5/6 nephrectomized rats:
      development of a new animal model.
AB  - BACKGROUND: We require a stable model to understand the molecular mechanism by
      which isolated hyperphosphatemia induces hyperparathyroidism secondary to chronic
      renal failure. The present study established a rat model of hyperphosphatemia
      induced secondary hyperparathyroidism in chronic renal failure. METHODS: Twenty
      nine rats with 5/6 nephrectomy (Nx) were divided into three groups and were fed
      for 10 weeks on a high phosphate diet (1.2% phosphate) starting from three
      different post-Nx time points. Parathyroid hormone mRNA in parathyroid gland was
      measured by real-time PCR and parathyroid cell hyperplasia was tested by
      proliferating cell nuclear antigen (PCNA) assay. RESULTS: The 10 rats fed a high
      phosphate diet starting from the fourth week post-Nx had isolated
      hyperphosphatemia and excess synthesis/secretion of parathyroid hormone, and
      hyperplasia of the parathyroid glands were induced (r = 0.86 - 0.97, P < 0.001),
      but the levels of serum calcium and 1, 25 (OH)2D3 did not change. CONCLUSION: A
      rat model of hyperphosphatemia-induced secondary hyperparathyroidism in chronic
      renal failure was established by 5/6 Nx and 10 weeks-high phosphate diet starting
      from the fourth week post-Nx.

PMID- 19102964
TI  - Effects of gonadotropin-releasing hormone antagonists on the expression of
      vascular endothelial growth factor and its receptors in a rat model of ovarian
      hyperstimulation syndrome.
AB  - BACKGROUND: Ovarian hyperstimulation syndrome (OHSS) is one of the most life
      threatening complications of assisted reproduction treatments. Gonadotropin
      releasing hormone antagonists (GnRHanta) are thought to be effective in
      preventing this complication, and some clinical trials have found lower
      incidences of OHSS in patients treated with GnRHanta. Our aim was to investigate
      the effects of GnRHanta on vascular permeability and the expression of vascular
      endothelial growth factor (VEGF) and its receptors in a rat model of OHSS.
      METHODS: An immature early OHSS rat model was established. Three ovarian
      stimulation protocols were used: pregnant mare serum gonadotropin/human chorionic
      gonadotropin (hCG) alone, with a GnRHanta, or with a gonadotropin-releasing
      hormone agonists (GnRHa). Blood and tissue samples were collected at 48 hours
      after hCG administration. Vascular permeability was evaluated by measuring the
      Evans-Blue content of extravasated peritoneal fluids. The expression of VEGF and
      its receptors, including flt-1 and KDR, were detected by reverse transcriptase
      polymerase chain reaction and Western blotting. RESULTS: Treatment with both a
      GnRHanta and a GnRHa resulted in significant reductions in serum estradiol and
      peritoneal vascular permeability, as well as decreased ovarian expression of VEGF
      and its two receptors. However, GnRHanta treatment caused a greater reduction in
      serum estradiol concentrations, and in VEGF receptor mRNA expression than GnRHa.
      There were no significant reductions in the expression of VEGF or its receptors
      in extra-ovarian tissues, including the liver, lungs and peritoneum. CONCLUSION:
      Our results reveal that GnRHanta are more potent than GnRHa in preventing early
      OHSS through down-regulation of the expression of VEGF and its receptors in
      hyperstimulated ovaries.

PMID- 19102966
TI  - Functional protection of pentoxifylline against spinal cord ischemia/reperfusion
      injury in rabbits: necrosis and apoptosis effects.
AB  - BACKGROUND: Little is known about neuronal death mechanisms following spinal cord
      ischemia. The present study aimed to investigate the protective effect of
      pentoxifylline (PTX) against spinal cord ischemia/reperfusion (I/R) injury.
      METHODS: Rabbits sustained spinal cord ischemia following 45 minutes cross
      clamping of the infrarenal aorta. Experimental groups were as follows: the first
      group of animals (sham, n = 8) underwent laparotomy alone and served as the sham
      group; the second group (I/R, n = 20) received carrier (3 ml saline solution) and
      served as the control group; the third group (PTX-A, n = 20) received PTX
      intravenously 10 minutes prior to ischemia; and the fourth group (PTX-B, n = 20)
      received PTX intravenously at the onset of reperfusion. Rabbits were evaluated
      for hind-limb motor function with the Tarlov scoring system at 48 hours. Serum
      was assayed with enzyme-linked immunosorbent assay for tumor necrosis factor
      alpha (TNF-alpha) and spinal cords were harvested for myeloperoxidase (MPO)
      activity, histopathological analysis, terminal deoxynucleotidyl transferase (TdT)
      mediated dUTP nick end labeling staining, platelet/endothelial cell adhesion
      molecule-1 (PECAM-1) and caspase-3 immunohistochemistry, and the number of
      necrotic and apoptotic neuron were counted and data analyzed at 12, 24, 48 and 72
      hours of reperfusion. Spinal cords were studied by electron microscopy. RESULTS:
      Improved Tarlov scores were seen in PTX-treated rabbits as compared with ischemic
      control rabbits at 48 hours. A significant reduction was found in TNF-alpha in
      serum, activity of MPO and immunoreactivity of the PECAM-1 and caspase-3 in PTX
      treated rabbits. There were fewer apoptotic neurons than necrotic neurons (P <
      0.05). A significant decrease in both necrotic and apoptotic neurons was observed
      in the PTX-treated groups (PTX-A and PTX-B) compared with the I/R group (P <
      0.05). Both necrotic and apoptotic neurons were found with the electron
      microscope. CONCLUSIONS: PTX may induce protection against ischemia injury in the
      spinal cord, thereby preventing both necrosis and apoptosis. A major mode of cell
      death in spinal cord ischemia/reperfusion injury is necrosis while apoptosis is
      not dominant.

PMID- 19102967
TI  - Spontaneous coronary dissection associated with myocardial bridge causing acute
      myocardial infarction.

PMID- 19102968
TI  - Acute and reversible cardiomyopathy provoked by stress in a Chinese woman.

PMID- 19102969
TI  - The clinical features and meningeal histochemistry of meningeal malignant
      melanosis.

PMID- 19102970
TI  - A novel flexible endoscope-based transumbilical fenestration of liver cyst.

PMID- 19102971
TI  - Transumbilical single-port laparoscopic cholecystectomy: a case report.

PMID- 19102972
TI  - Cases of dengue fever on rise in Vietnam.

PMID- 19102973
TI  - [Discussion on the fluid resuscitation and monitoring during burn shock period].
AB  - The index of monitoring burn shock resuscitation includes clinical signs and
      symptoms, laboratory examinations, hemodynamic variables. In recent years, there
      exists a tendency that the amount of transfused fluid for burn shock
      resuscitation is notably increased and complications of some cases, such as
      abdominal compartment syndrome have been reported. One of the major reasons for
      excessive fluid resuscitation is to try to normalize hemodynamic parameters with
      the help of invasive hemodynamic monitoring. Instead of hemodynamic variables,
      urinary output combined with other traditional variables still should be
      considered primary criteria of adequate fluid therapy. Specification of the
      variables of monitoring burn shock resuscitation is also the basis to revise and
      optimize the fluid resuscitation formula.

PMID- 19102974
TI  - [Pay great attention to research on monitoring burn shock].
AB  - Improvement in early burn treatment has been realized, the mortality of burn
      shock has been decreased. However, the treatment of burn shock is still
      inadequate and occult hypoperfusion is usually occurred. This may be difficult to
      identify the appropriate resuscitation endpoint. The goal in management of burn
      shock is restoration of adequate tissue perfusion and normalization of cellular
      metabolism. Traditional endpoints, such as blood pressure, urine output are
      useful in managing mild and moderate burn shock. Additional endpoints that
      evaluate the adequacy of global and regional perfusion and oxygenation at the
      tissue level should be used in treatment of severe burn injury. Now the most
      useful parameters may be blood pressure, urine output, serum lactate, BE and CVP,
      SCVO2.

PMID- 19102975
TI  - [Clinical practice and evaluation of relative fluid resuscitation formula at burn
      shock stage].
AB  - OBJECTIVE: To evaluate the application of the Third Military Medical University
      (TMMU) formula for fluid resuscitation on the major burn patients during shock
      stage. METHODS: Seventy-one thermal injury patients (burn area more than 30%
      TBSA, without especial illness, hospitalization within 8 hour after burn)
      admitted from 2005 to 2007 were divided into adult group (n = 46), child group (n
      = 25). Fluid resuscitation was initiated as per the TMMU formula. RESULTS: All
      patients survived the first 48 hours post burn injury and none developed
      recognized complications associated with fluid resuscitation. The average infused
      fluid was 16% approximately 38% more than the calculated in both adult and child
      groups. The average urine output during the first 24 hours post burn injury was
      1.1 approximately 1.2 mL x kg(-1) x h(-1) in the two groups, but reached 1.2 mL
      and 1.7 mL x kg(-1) x h(-1) during the second 24 hours in adult and child groups
      respectively. CONCLUSION: TMMU formula for fluid resuscitation is a feasible
      option for major burn patients. Individual fluid resuscitation, guided by the
      physiological response, is also important and necessary.

PMID- 19102976
TI  - [Protective effect of lytic cocktail (inhibition of stress) on lung injury in
      severe burn rat].
AB  - OBJECTIVE: To investigate the protective effect of inhibition of stress (lytic
      cocktail) on lung injury in severe burn rats at early stage. METHODS: Sprague
      Dawley rats inflicted with 30% TBSA full-thickness burn were randomly divided
      into A group (n = 36, fluid resuscitation with administration of lytic cocktail),
      B group (n = 36, fluid resuscitation only). Lung function was evaluated by
      partial pressure of oxygen (PaO2) in arterial blood and histopathologic changes
      on 3, 5, 7, 10 post burn day (PBD). The levels of malonyldialdehyde (MDA),
      myeloperoxidase (MPO), tumor necrosis factor-alpha(TNF-alpha) and interferon
      gamma (IFN-gamma) in lung tissue were measured at the same time points. RESULTS:
      The PaO2 level in A group on 3 PBD (12.58 +/- 0.41 kPa) was significantly higher
      than that in B group (8.86 +/- 0.23 kPa, P < 0.01). Compared with those in B
      group, the levels of MDA and MPO were significantly decreased in A group at each
      time point (P < 0.05 or 0.01), the levels of TNF-alpha on 3, 5, 7 PBD (P < 0.05
      or 0.01) and IFN-gamma on 5, 7, 14 PBD (P < 0.01) were also decreased in A group.
      Swollen lung mesenchyme was alleviated, infiltration of inflammatory cell was
      lessened in A group. CONCLUSION: Lytic cocktail combined with immediate fluid
      resuscitation can inhibit stess response, downregulate the expression of
      inflammatory factor, ameliorate lung function in severe burn rat at early stage.

PMID- 19102977
TI  - [Improving myocardial mechanics parameters of severe burn rabbits with oral fluid
      resuscitation].
AB  - OBJECTIVE: To investigate the protective effect of oral fluid resuscitation on
      cardiac function in severe burn rabbits. METHODS: One hundred and fifty rabbits
      were randomly divided into normal control group (NC group, n = 6, without
      treatment), burn group (B group, n = 42, without fluid therapy), immediate oral
      fluid resuscitation group (C group, n = 42), delayed oral fluid resuscitation
      group (D group, n = 30) and delayed and rapid oral fluid resuscitation group (E
      group, n = 30). The rabbits in B, C, D, E groups were subjected to 40% TBSA full
      thickness burn, then were treated with fluid therapy immediately after burn (C
      group), at 6 hour after burn (D, E groups). The myocardial mechanics parameters
      including mean arterial pressure (MAP), left ventricular systolic pressure
      (LVSP), left ventricular end diastolic pressure (LVEDP), LV +/- dp/dt max were
      observed at 2, 6, 8, 12, 24, 36 and 48 post burn hour (PBH). Urine output was
      also examined. RESULTS: The level of LVSP, LV +/- dp/dt max in B roup were
      significantly lower than those in NC group. The level of LVSP, LV +/- dp/dt max
      in the C and E group were singnificantly increased during 24 hour after burn. The
      level of LV + dp/dt max and LV-dp/dt max in C group peaked at 8 PBH (892 +/- 116
      kPa/s) and at 6PBH (724 +/- 149 kPa/s) respectively. The levels of LV +/- dp/dt
      max, LVSP in D group at each time point were similar to B group (P > 0.05). Both
      the levels of LV +/- dp/dt max in E group peaked at 8 PBH. The level of LVEDP was
      no obvious difference between B and other groups at each time point (P > 0.05).
      The changes of MAP and urine output on 24 PBH in each group were similar to above
      indices. CONCLUSION: Effective oral fluid therapy in severe burn rabbits during
      24 hours after burn can ameliorate myocardial mechanics parameters. The amount of
      fluid resuscitation can be estimated according to relevant formula for delayed
      fluid resuscitation in burn rabbits.

PMID- 19102978
TI  - [The effect of stimulation of toss simulated at sea on shock in severe burn
      rabbits].
AB  - OBJECTIVE: To investigate the effect of stimulation of toss simulated at sea on
      shock in severe burn rabbits. METHODS: One hundred and thirty-two rabbits were
      randomly divided into normal control group (NC group, n = 6), toss group (T
      group, with treatment of continuous toss, n = 42), burn group (B group, with
      treatment of burn, n = 42), burn and toss (BT group, with treatment of continuous
      toss after burn, n = 42). The level of Cr, BUN, HCT and LA from blood samples in
      T, BT, B groups were observed at 2, 6, 8, 12, 24, 36, 48 post treatment hour
      (PTH). The changes in urinary volume was measured during 48 PTH. The
      histopathologic changes in kidney were observed at above-mentioned time points.
      The above indices in NC group were also observed. RESULTS: The mean urinary
      volume in B group during the first and second 24 PTH was (2.59 +/- 0.23) and
      (2.86 +/- 0.29) mL/h, while that in BT group was (1.61 +/- 0.13) and (1.66 +/-
      0.16) mL/h respectively, which were all lower than those in NC group (6.06 +/-
      0.18 mL/h, P < 0.01). The levels of HCT and LA in BT group were obviously higher
      than those in B group at each time point. The levels of Cr and BUN in BT group at
      24, 36, 48 PTH were significantly higher than those in B group. The
      histopathological observation showed the capillary vessels and mesenchymal cells
      of kidney glomerulus were congestive, epithelial cells in kidney tubules were
      swollen. The infiltration degree of inflammatory cells in kidney tubule, and the
      pathological changes of erythrocyte cast in BT group were more serious than those
      in B group. CONCLUSION: The toss simulated at sea can significantly aggravate
      shock and the renal damages in severe burn rabbits.

PMID- 19102980
TI  - [Study on crosstalk between phosphatidylinositol 3 -kinase/Akt pathway and p38
      mitogen-activated protein kinase pathway in cardiomyocyte with challenge of burn
      serum].
AB  - OBJECTIVE: To investigate the possibility of crosstalk between
      phosphatidylinositol 3-kinase (PI3-K)/Akt pathway and p38 mitogen-activated
      protein kinase (p38MAPK) pathway in cardiomyocyte with challenge of burn serum,
      and to explore their influence on cardiomyocyte injury after burn. METHODS: The
      model of murine cardiomyocyte with stimulation of burn serum was established. (1)
      The level of Akt and p38 phosphorylation in cardiomyocyte were examined with
      stimulation of 10% burn serum before stimulation and 1, 3, 6, 12, 24 hour after
      stimulation. (2) The levels of Akt and p38 phosphorylation in cardiomyocyte were
      determined with stimulation of burn serum (at concentration of 5%, 10%, 20%) or
      10% burn serum plus insulin (at concentration of 1 x 10(-8), 1 x 10(-7), 1 x 10(
      6)mol/L). The content of creatine kinase (CK) in supernate was also detected. (3)
      Addition to the inhibitor of p38 MAPK pathway (SB203580) and PI3K/Akt pathway
      (LY294002), the level of p38MAPK, PI3K/Akt and the content of CK in supernate
      were determined. RESULTS: (1) The level of p-p38 in cardiomyocyte was 4.0 +/-
      0.8, 3.6 +/- 0.8, 5.1 +/- 1.6, 2.4 +/- 0.5, 3.0 +/- 0.6 at 1, 3, 6, 12, 24 hour
      (s) after stimulation of burn serum, which was obviously higher than that
      immediate after stimulation (1.0, P < 0.01). The level of p-Akt was 0.15 +/-
      0.07, 0.64 +/- 0.10, 0.26 +/- 0.08, 0.38 +/- 0.11, 0.59 +/- 0.13, which was
      obviously lower than that before stimulation (1.00, P < 0.01). (2) With
      stimulation of different concentration of burn serum or burn serum plus insulin,
      the level of p-Akt and p-p38 changed in the opposite directions comparatively.
      The content of CK increased along with increase of burn serum concentration, but
      decreased obviously with treatment of insulin (P < 0.05 or 0.01). (3) Low level
      of p38 induced by burn serum was increased after treatment of LY294002, which
      neutralized the protection of insulin (P < 0.01). Low level of p-Akt induced by
      burn serum increased after treatment of SB203580 (P < 0.01), which inhibited the
      release of CK induced by burn serum. CONCLUSION: There is being crosstalk between
      PI3K/Akt pathway and p38 MAPK pathway in cardiomyocytes with challenge of burn
      serum, which may regulate cardiomyocytes.

PMID- 19102982
TI  - [Repair of claw hand deformity after burn].
AB  - OBJECTIVE: To summarize methods for repair of claw hand deformity after burn.
      METHODS: Ninety-seven patients with 136 claw hands after burn hospitalized from
      May 1992 to May 2007 were repaired with skin grafting (104 hands) and
      transposition of skin flap (32 hands), among which 21 hands were minor-grade, 92
      hands moderate, 23 hands severe. The metacarpophalangeal joint was repaired after
      scar release in dorsum of hand with manual extraction reduction, release of
      collateral ligament and joint capsula, separation of adhesion in joint, tendon
      lengthening for obvious contracture. Restitution of finger flexion deformity,
      lysis of adhesion and grafting among first web and finger webs, repair of central
      slip extensor tendon or phalangeal arthrodesis were performed according to the
      abnormal condition after lysis of dorsal scar of hand. The metacarpophalangeal
      joint from 31 patients were not repaired with above methods for severe finger
      flexion deformity, their palmar scar were loosened and transplanted firstly, then
      scar in dorsum of hand were loosened, metacarpophalangeal joint were repaired,
      flap or skin were transferred or transplanted. General rehabilitation were
      performed routinely after operation. RESULTS: The ending of flaps (4 hands) due
      to the scar were necrosis after transposition and healed through dressing change,
      other skins or flaps all survived. Most articular deformities were corrected
      completely or basically. Functions including palmar opposition, grasp were also
      recovered with satisfactory results. CONCLUSION: Skin transplantation and
      transferring of skin flap with overall planning and individual isatin are the key
      points for repair of claw hand after burn.

PMID- 19102983
TI  - [Construction of tissue-engineering skin with carrier of active composite dermal
      matrix].
AB  - OBJECTIVE: To construct of tissue engineering skin including active composite
      dermal matrix. METHODS: The human fibroblasts and bovine collagen with type I
      were inoculated on the surface of porcine acellular dermal matrix (PADM) for
      construction of active dermal substitute, then epidermal cells were inoculated on
      the dermal matrix for gas-liquid interface culture. The tissue-engineering skin
      was observed by histological examinations. RESULTS: The structure of fibroblasts
      in collagen was intact, which was used to construct composite dermal matrix with
      PADM. The epithelial structure of tissue-engineering skin was similar to that of
      normal skin with good cell differentiation. Some phenomena were showed in
      epidermis: basic layer, stratum spinosum, granular layer and stratum corneum,
      desmosomes. CONCLUSION: Fibroblasts-Collagen-PADM can be an optimal dermal matrix
      for construction of tissue-engineering skin.

PMID- 19102984
TI  - [Effect of transfection of recombinant human endothelial nitric oxide synthase
      gene on hypertrophic scar fibroblasts in vitro].
AB  - OBJECTIVE: To investigate the feasibility of transfection of recombinant human
      endothelial nitric oxide synthase (eNOS) into human hypertrophic scar fibroblasts
      (HSFbs), and to observe NO secretion and the synthesis of collagen I and III.
      METHODS: Recombinant human eNOS with karyocyte expressive vector was constructed
      in vitro, then was transfected into HSFbs which was isolated from hypertrophic
      scar tissues and cultured in vitro (T group). The HSFbs untransfected (normal
      culture) or transfected with empty-vector was used as control group and empty
      vector group respectively. The mRNA expression of eNOS, collagen I and III was
      determined by Realtime PCR. The content of NO was determined by NO assay kit.
      RESULTS: The expression of eNOS mRNA in T group was 5.92 +/- 0.21, which was
      obviously higher than that in empty-vector group (0.98 +/- 0.13, P < 0.05). The
      expression of collagen I mRNA (0.76 +/- 0.15), and collagen III (0.79 +/- 0.08)
      in T group was significantly lower than those in empty-vector group (0.98 +/-
      0.15, 1.02 +/- 0.12, P < 0.05, respectively). The content of NO in T group (36.1
      +/- 0.8 micromol/L) was obviously higher than that in empty-vector group (28.4 +/
      1.0 micromol/L, P < 0.01) and control group (27.7 +/- 1.3 micromol/L, P < 0.01).
      CONCLUSION: HSFbs can be the target cells for eNOS gene transfection. The
      transfected cells can express eNOS and produce NO, which inhibit the synthesis of
      collagen.

PMID- 19102985
TI  - [Study on activation of mitogen-activated protein kinase pathway in lung tissue
      of rats with smoke inhalation injury].
AB  - OBJECTIVE: To investigate the activation of mitogen-activated protein kinase
      (MAPK) pathway and the expression of inflammatory cytokine in lung tissue of rats
      with smoke inhalation injury, and to explore the injury mechanism. METHODS: The
      model of smoke inhalation injury in airtight cabin was established. Thirty-six SD
      rats were randomly divided into normal control group (n = 6, NC group) and
      inhalation injury group (n = 30, II group). The rats in II group were observed at
      1, 6, 24, 72 post injury hour (PIH) and 7 post injury day (PID). The pathological
      changes in lung tissue were observed by optical microscope. The contents of TNF
      alpha, MIP-2, IL-1beta in lung tissue homogenate were examined. The level of
      p38MAPK, JNK, ERK1/2 and their phosphorylation in lung tissue were measured by
      Western blotting. The contents of TNF-alpha, MIP-2, and IL-1beta and granulocytes
      counts in BALF (bronchoalveolar lavage fluid) were detected by ELISA. RESULTS:
      Pathological change of smoke inhalation was similar to acute lung injury. The
      contents of TNF-alpha and IL-1beta of lung tissue and BALF in II group at 1 PIH
      were higher than those in NC group (P < 0.01). The levels of MIP-2 of lung tissue
      in II group at each time point were similar to that in NC group (P > 0.05), while
      that of BALF in II group at 1 PIH were obviously higher than that in NC group (P
      < 0.01). Compared with those in NC group, the levels of p38MAPK, JNK, ERK1/2 in
      II group at each time point were similar, and their phosphorylation levels
      increased with different degree. Compared with that in NC group [(0.61 +/- 0.09)
      x 10(6) cells/L], the total number of granulocytes in II group was significantly
      decreased at 1PIH [(0.36 +/- 0.08) x 10(6) cells/L], increased on 7PID [(1.71 +/-
      0.67) x 10(6) cells/L, P < 0.05]. The number of neutrophils in II group during
      6PIH approximately 7 PID were more than that in NC group. The number of
      lymphocyte in II group at 1PIH less than that in NC group (P < 0.05), which
      increased gradually during 6 PIH approximately 7PID. There were no obvious
      difference in number of lymphocyte between two groups (P > 0.05). CONCLUSION: The
      obvious inflammatory response in lung tissue can be induced by the poisonous gas
      released from the combustion of nonmetal materials in airtight cabin, and
      activate the expression of kinases in MAPK pathway, which may be one of
      mechanisms for lung injury induced by poisonous gas.

PMID- 19102987
TI  - [The protection of heme oxygenase-1 from acute cardiocyte injury in rats].
AB  - OBJECTIVE: To observe the protection of Heme oxygenase-1 (HO-1) from
      lipopolysaccharide (LPS)-induced cardiocyte injury and its mechanism. METHODS:
      Cardiocyte was isolated from SD neonate rat and cultured in vitro, and was
      divided into control group (normal culture), LPS group (with stimulation of 30
      micromoL/L LPS for 1 hour), LPS + Hemin group (with same treatment to LPS group
      after stimulation of 5 micromoL/L Hemin for 1 hour), and LPS + ZnPP group (with
      same treatment to LPS group after stimulation of 3 micromoL/L ZnPP for 1 hour).
      The level of lactic-dehydrogenase (LDH), malondialdehyde (MDA), superoxide
      dismutase (SOD) were measured by thio-barbituric acid and xanthine oxidase
      techniques. The cell heart rhythm, survival rate and apoptosis rate were
      examined. The expressions of nuclear factor kappaB (NF-kappaB), HO-1 and tumor
      necrosis factor-alpha (TNF-alpha) were measured with Western blotting. The HO-1
      mRNA was examined by RT-PCR. RESULTS: The level of LDH and MDA in LPS, LPS +
      Hemin, and LPS + ZnPP groups were (113 +/- 15), (79 +/- 13), (154 +/- 22) U/L,
      and (1.88 +/- 0.36), (1.16 +/- 0.32), (2.84 +/- 0.44) mmoL/L respectively, which
      were all obviously higher than those in control group [(69 +/- 10) U/L, (0.87 +/-
      0.25) mmol/L, P < 0.05]. The level of SOD in LPS, PS + Hemin, and LPS + ZnPP
      groups (17.8 +/- 1.8, 22.5 +/- 2.4, 13.4 +/- 1.5 U/mL, respectively) was all
      obviously lower than that in control group (24.3 +/- 3.6 U/mL, P < 0.05). The
      apoptosis rate and heart rhythm were obviously higher and survival rate
      significantly lower in LPS, LPS + Hemin, and LPS + ZnPP groups than those in
      control group (P < 0.05). The level of HO-1mRNA in LPS, LPS + Hemin, and LPS +
      ZnPP groups was higher than that in control group (P < 0.01), among which LPS +
      Hemin group was the highest. The level of HO-1, TNF-alpha and NF-kappaB in LPS,
      LPS + Hemin, and LPS + ZnPP groups was higher than those in control group (P <
      0.05), among which the level of HO-1 protein in LPS + Hemin group was the
      highest, the level of TNF-alpha and NF-kappaB in LPS + ZnPP group was highest.
      CONCLUSION: LPS can induce cardiocyte injury, which can be inhibited through the
      anti-inflammatory, anti-oxidant, and anti-apoptosis functions by HO-1.

PMID- 19102988
TI  - [Treatment of burn cicatricial foot drop with Ilizarov fixator].
AB  - OBJECTIVE: To investigate the efficacy of Ilizarov fixator on cicatricial foot
      drop after burn. METHODS: Six patients with cicatricial foot drop after burn were
      treated with Ilizarov fixator during June 2004 approximately October 2007, the
      fixator was set on the leg and foot by fixed bone needles. Nuts on the threaded
      rod were turned from 3 post operation day, 2 approximately 4 rounds per time and
      4 times per day in the first week, then 1 approximately 2 rounds per time and 4
      times a day, which corrected the deformity of talipes equinus by shortening or
      lengthening the thread rod in the front and at the back. Ankle joint was
      maintained in neutral position for 2 approximately 3 months after effective
      correction. Weight carrying for patients was increased gradually after removal of
      fixator. Ankle joint was maintained in neutral position with fixator at least
      three months. Patients were followed up 5 approximately 10 months. RESULTS: Ankle
      joints from all patients were restored to neutral position after application with
      fixator for 4 approximately 6 weeks. All patients achieved 0 degrees dorsiflexion
      in weight carrying for whole planta pedis after use of fixator for 12
      approximately 15 weeks with good locomotion function. CONCLUSION: Ilizarov
      fixator is safe and mini-injury, which is an effective method for treatment of
      cicatricial foot drop.

PMID- 19103004
TI  - [Achievements in burn surgery over the past 50 years in China].
AB  - This paper reflects briefly the main advancements of clinical and scientific
      research in the field of burn surgery over the past 50 years in China. It
      includes emergency care of massive burns, resuscitation, anti-infection,
      prevention and treatment of internal organ injury, metabolic and nutritional
      support, repair of wound and rehabilitation, and special types of burns. The
      article also covers the researches in pathology, microbiology, immunology, cell
      biology, molecular biology, and tissue engineering pertaining to burn injury.

PMID- 19103005
TI  - [A review of 50 years investigation on burn pathology in China and its prospect].
AB  - A great achievement has been made on burn pathology research in China since 1958.
      These advances include: pathological changes in burn wound, the healing process
      of burn wound and its mechanism modulated by growth factors especially bFGF,
      intermingled transplantation of allo-skin or xeno-skin with auto-skin for
      coverage of extensive third degree burns, characteristic postburn inflammatory
      reaction, pathological changes and evolution in various internal organs, multiple
      organ dysfunction syndrome (MODS), pathological changes in phosphorus burn,
      pathological changes in endotoxemia in burn, the role of vascular endothelial
      cell in pathogenesis of postburn visceral organ dysfunction as well as steam and
      smoke inhalation injury.

PMID- 19103006
TI  - [Experiences in rescue and treatment of mass burn casualties in fifty years].
AB  - The article reviewed the history and the main experiences of rescue of mass burn
      casualties and their treatment during the past fifty years in China. Some issues
      including medical support for mass burn casually and treatment regime in future,
      such as the prevention of burn calamities, further elevation of the cure rate and
      lowering in the rate of disability, further development in network of burn care
      and preliminary scheme of rescue of mass burn casualties and their treatment,
      accelerating the development and study on the substitutes of allo-skin graft were
      discussed.

PMID- 19103007
TI  - [Retrospection and recent advances in fluid resuscitation during burn shock
      stage].
AB  - To retrospect the development of fluid resuscitation for burn shock and to look
      to the future. The main achievements in burn care in the past fifty years and
      existing problems are summarized, and the appropriate regime of fluid
      resuscitation for burn shock is suggested. Numerous achievements in burn care
      have been made, including the estimation of burn area, fluid replenishment
      formula, delayed resuscitation, fluid resuscitation for burn shock complicated by
      inhalation injury, covert compensatory shock and research on mechanism of burn
      shock etc. We had established and improved fluid resuscitation formula, and we
      had made clear how to properly resuscitate burn shock. However how to tide over
      the patient form burn shock smoothly had not yet reached a consensus. Effective
      treatment to alleviate hypoxic injuries as a result of severe shock had not been
      properly defined. Although significant achievements in fluid resuscitation for
      burn shock have been made, there is still a long way to go to attain a perfect
      regime. Therefore it is still utterly necessary to carry on in-depth research on
      this problem both in the laboratory and bedside.

PMID- 19103008
TI  - [The gut-origin infection in severe burns].
AB  - Early in 1962, after an extensive review including 312 cases of bacteremia in
      burn patients, we were surprised to find that there was about 30% of bacteremia
      in the patients who had no detectable microorganisms from repeated wound
      cultures, but blood cultures were usually positive for gut flora. From that time
      on the idea of gut-origin infection emerged. In following twenty years, a series
      of experiments were carried on in Wistar rats with 30% TBSA full-thickness burn.
      The results showed that the fluorescein labeled enteric microbes (Pseudomonas
      aeruginosa, Bacteroid fragilis and Candida albicans) could translocate through
      the stress injured intestinal wall and were recovered in visceral organs. The
      radioisotope 125I labeled endotoxin began to ascend in concentration in portal
      vein since 15 minutes postburn. Radioautography of liver sections demonstrated
      the labeled endotoxin granules. With the creation of minute mesenteric lymph
      fistulas, the clearance of endotoxin and TNFalpha was found to be significantly
      high in lymph fluid exited from the intestine. All above evidences indicated that
      the gut is a potential route of endogenous infection, and it also explained how
      did the patients manifest sepsis early after burn injury without a definite
      infectious focus. Now the concepts of gut-origin infection are commonly accepted,
      the measures like early enteral feeding for the protection of intestinal barrier
      has been established.

PMID- 19103009
TI  - [Bacterial ecology on burn wound and antibacterial agent therapy].
AB  - The main factors influencing the bacterial ecology on burn wound are the
      selection of antibacterial agents and systemic antibiotic. Some antibacterial
      agents more active against P. aeruginosa were developed in 1960s, and the
      detection rate of P. aeruginosa on burn wound has been declined, and the
      detection rate of Enterobacteriaceae species and Acinetobacter SPP. has been
      raised since then. In 1990s, the third generation Cephalosporin was widely used
      in burn unit and the detection rate of staphylococcus aureus showed an increased
      trend. Especially, the positive rate of MRSA was increased significantly. Under
      the selection pressure of antibacterial agent, the resistant strains are rapidly
      increased and the antibiotics against opportunistic pathogen on burn wound should
      be selected continuously. Finally, the bacterial ecology pattern on burn wound is
      changing incessantly. The result is that the prevalence of infection of multi
      drug resistance strains and opportunistic pathogen appears on burn wound. In
      order to optimize the antibiotic therapy, the bacterial ecology pattern on burn
      wound has to be investigated, and the dominant pathogen including invasive and
      currently prevailing strains in the burn unit also should always be surveyed. In
      addition, we also should know the mechanisms of bacterial resistance. The regular
      surveillance of antibiotic resistance in the clinical isolates is the most
      important and valuable for understanding the trend of bacterial resistance. The
      antibiotic therapy should be decided according to the result of susceptibility
      tests.

PMID- 19103010
TI  - [The pathogenesis and management of severe sepsis after burns].
AB  - Sepsis and septic shock as a result of an invasive infection are challenging
      problems in extensively burned patients, and frequently end in multiple organ
      dysfunction syndrome (MODS). It is of great significance to further elucidate the
      pathogenetic mechanisms, and to seek novel intervention strategies to prevent and
      treat sepsis/MODS secondary to severe burns. A more complete understanding of the
      pathogenetic mechanisms of postburn sepsis would certainly elicit a number of
      potential therapeutic strategies for it. It is our belief that comprehensive
      clinical measures for management of severe sepsis should include rapid, adequate
      fluid resuscitation for burn shock, early feeding, effective control of
      infection, early escharectomy, and reinforcement of organ support. Once burn
      wound sepsis occurs, prompt removal of infected necrotic tissue is the key
      procedure to ensure a successful result. Further study is necessary to determine
      the precise mechanisms of these protective effects and the clinical advantages
      for postburn sepsis using evidence-based methodology system.

PMID- 19103011
TI  - [The intermingled transplantation used in severe burn patients after eschar
      excision].
AB  - In the early developing stage of burn surgery, severe burn patients with large
      and deep burn wound often died of complications because of shortage of auto-skin.
      The method of intermingled transplantation composed of a large sheet of partial
      thickness allo-skin with punched holes for in laying small pieces of partial
      thickness auto-skin was first advocated by Chinese doctors (Ruijin Hospital) in
      1960's. This intermingled transplantation method has saved many severe burn
      patients with extensive full-thickness burn wound. The mortality rate of severe
      burn patients has decreased and the survival rate has increased remarkably since
      the intermingled transplantation treatment method used in the burn units. In this
      paper we review the process of formation of intermingled transplantation and the
      mechanisms of success of this Chinese method in repairing the large wound surface
      area after eschar excision. We will focus our discussion on the low systemic
      immunological reaction, the effect of auto-skin islet, local immunological
      tolerance induced by in layed auto skin, the balance of Th1 and Th2 cells and the
      effects of some cytokines such as IL-10 in local immunological tolerance and etc.
      after intermingled transplantation.

PMID- 19103012
TI  - [Retrospection and future of microskin grafting].
AB  - Since microskin grafting was used in 1985, 23 years have passed. Many patients
      with extensive third degree burns were cured by the technique. Some progresses
      and further improvements are discussed. (1) Several kinds of apparatus were
      devised to cut skin into micrografts with good results. (2) The orientation of
      each skin granule and even dispersion of micrografts are very important. Some
      methods to spread micrografts on wound were compared with one another, the
      technique of flotation in saline and transferring them on silk texture is still
      the best way. (3) Many outside materials other than silk can be selected, among
      them the homograft is commonly used, but it has some shortcomings. (4) The
      technique should be further improved. Stem cell transplantation may be expected
      as a new way to help heal extensive wounds.

PMID- 19103013
TI  - [Application of topical drugs in burn wound].
AB  - For burn patients, topical treatment is as important as systemic treatment.
      Reasonable and timely wound treatment will influence the homeostatic equilibrium,
      and the progression, the prognosis, and the outcome of the disease. The
      therapeutic principle should be varied for wounds with different depth of injury.
      But avoiding or at least alleviating infection, and accelerating healing period,
      were the common principles. In common, the medication for local wound treatment
      includes: topical antiseptic, surgical dressing products, artificial skins, and
      so on. Ideal topical antiseptic should have the following characteristics: the
      antimicrobial spectrum is broad, including Pseudomonas aeruginosa and MRSA; be
      able to penetrate necrotic tissue; does not induce drug resistance easily; no
      local irritating effect and not painful; no side effect to body;can be applied
      easily; low cost. The functions of surgical dressing include: protect the wounds,
      keep the microcirculation open, and accelerate wound healing. Artificial skin has
      been used as the autoskin carrier in skin transplantation operation for large
      burn area to protect the autoskin grafts, accelerate wound healing, and cover the
      wounds temporarily. Burns therapy has developed for 50 years in China, the study
      of local treatment for burn wounds has also experienced a tortuous path of trial
      and error. This review might contribute some ideas future research.

PMID- 19103014
TI  - [The study in immunology after skin transplantation].
AB  - Skin grafting has been one of the most important approaches for covering burn
      wounds, however long-term survival of allogeneic or xenogeneic skin graft is
      currently not successful. How to induce immune tolerance for life-time survival
      of allogeneic or xenogeneic skin graft is still remote objective to be solved.
      However, clinicians and scientists in China have worked very hard and made great
      contribution to this field during the past 50 years, no matter how difficult it
      is. They are the respected pioneers in the understanding of immunological change
      in "Chinese Method" skin grafting, its local immune tolerance, immunology of pre
      treatment of skin graft, etc. Herein, the most outstanding and impressive
      progresses in immunological responses after skin grafting in the past 50 years in
      China have been reviewed and presented for memory, for future and for extending a
      salute.

PMID- 19103015
TI  - [Application of skin flaps transplantation in burn surgery in China].
AB  - The history and application of surgical flap transplantation in burn wound were
      briefly reviewed. We outlined skin flap, musculocutaneous flap, fascia flap and
      neurocutaneous vascular flap in this paper and recommended repair deep wounds
      with flap. All in all, in this review, we hope to provide a meaningful option for
      clinical application of surgical flap in the future.

PMID- 19103016
TI  - [Functional reconstruction of multiple severe deformities after extensive deep
      burn].
AB  - To explore new measures for functional reconstruction of multiple severe
      deformities as a result of extensive deep burn (total burn surface area > or =
      90% TBSA, including deep burn > or = 70%TBSA) in late stage. Twelve severe burn
      patients with above-mentioned deformities were hospitalized in our ward during
      1960--2005, the scars resulted from burns were distributed from head to foot with
      173 deformities, including 27 scar ulcers. All patients lacked of self-care
      ability, among them some could not stand. Due to inadequate skin source,
      deformities were corrected by skin from matured scars expanded with subcutaneous
      balloon at late postburn stage. Following our former clinical experience,
      anatomic investigation and experimental research, we chose the following methods
      to correct deformities and restore functions: application of split-thickness scar
      skin after expansion (88 wounds); use of scar skin flap/scar-Achilles tendon
      flaps (59 wounds); combination of thin split-thickness skin grafts from scar and
      allogeneic acellular dermal matrix (composite skin, 40 wounds). All grafts
      survived, the appearance and function were improved obviously without
      complications. Follow-up 1-40 years, all patients could take care themselves with
      satisfactory function and appearance, and among them 8 patients returned to work
      (one had worked for 40 years), 2 patients married and had children. The above
      mentioned measures are safe, reliable and effective for functional reconstruction
      of deformities.

PMID- 19103017
TI  - [Basic and clinical research in the field of burn wound healing].
AB  - The basic and clinical research in wound healing have made great progress in
      China in the past 50 years. The method of "intermingle skin transplantation"
      which was first advocated by surgeons of Ruijin Hospital in 1966 greatly reduced
      the amount of autologous donor skin, thus making the coverage of an extensive
      burn wound possible. This method is also known as "Chinese therapy". In 1986,
      doctors of Jishuitan Hospital reported successful coverage of an extensive burn
      wound with microautografts and allogeneic skin. The basic research of wound
      healing has been carried out since 1992, a series of studies showed the
      characteristics of biological behaviours of cells in concern, extracellular
      matrix and growth factor, the mechanism underlying progressive injury in deep
      second burn wound, the effect of "skin island" and the local immune tolerance
      induced by it (which are the key factors of intermingle transplantation). The
      induction of local immune tolerance has now become the research hot subject of
      skin transplantation immunology. Stem cell research in the field of wound healing
      has been extensively carried out. The theory of "dermal template defection" has
      been proposed as one of the mechanisms of scar formation. On the other hand,
      great progress has been achieved in the treatment of burns on the basis of
      clinical researches. Doctors of PLA 304 hospital found that excision of eschar on
      patients with extensive deep burn injury at early shock stage greatly decreased
      the occurrence of complications and mortality. Doctors of Ruijin Hospital
      reported that healing of deep second burn wound could be improved by tangential
      excision of burn eschar within 24 hours after burn injury. Doctors of Xiangya
      Hospital reported patients suffering from deep burns of the hands got satisfied
      functional restoration when treated with tangential excision of eschar while
      degraded dermal tissue could be retained with transplantation of autoskin grafts.

PMID- 19103018
TI  - [Skin tissue engineering in China].
AB  - Great progress has been made in the basic research and clinical application of
      skin tissue engineering in China over the past 20 years. It includes culture of
      epithelial cells and their preliminary clinical use, research and development of
      various dermal substitutes such as acellular dermal matrix, spongiform collagen
      membrane and high molecular weight polymer membrane, and modification of physical
      properties of dermal substitutes for the sake of raising their bioaffinity and
      vascularization, based on which composite skin containing epithelial cell layers
      has been constructed and used successfully in the repair of full-thickness skin
      defects. More recently, greater efforts have been made in the study of new
      epithelial seeding cells such as epithelial stem cell and hair follicle stem
      cell. With the work going into the center, it is hopeful into constructing an
      artificial skin that mimics the normal human skin in terms of structure and
      function with better viability of the transplant, so that it can eventually be
      used in clinical practice as a skin source for large area deep burn patients to
      improve the wound healing quality.

PMID- 19103019
TI  - [Stem cells and wound repair in burns].
AB  - The use of stem cells to replace lost tissues is one of the very important
      treatment measures used in the field of burn management in recent years. Clinical
      results show that the use of stem cells therapies has brought new hope for
      accelerating wound healing with improvement in quality, inducing sweat gland
      regeneration, and constructing tissue engineering skin, etc.

PMID- 19103020
TI  - [Signal transduction mechanism in burn wound healing].
AB  - After 50 years of development in science of burns care in China, we have
      basically solved coverage of deep wounds of burn trauma, as well as role of
      multiple growth factors and stem cell in wound healing, making great contribution
      to improving the treatment of patients with large area of deep burns. Surgeons
      are paying close attention to problems of wound healing, especially in the fields
      of scarless healing and rehabilitation. To solve these problems, we need to do
      further investigation on multiple growth factors as well as
      proliferation/differentiation of stem cells in regulation of cell growth and
      differentiation in wound healing. Therefore, we are facing a even more serious
      challenge.

PMID- 19103021
TI  - [Myocardial injury after burn at early stage and its treatment].
AB  - Ischemia/hypoxia is one of the key clinical issues following severe burns, and
      ischemic/hypoxic damage of tissues and organs is still hard to be prevented or
      minimized by various fluid resuscitation regimens. To those who suffered severe
      burns, even though fluid replacement therapy is delivered promptly,
      ischemic/hypoxic damage of organs is still inevitable. Previously, blood flow in
      vital organs such as heart was considered not to be reduced because of blood
      redistribution under the circumstance of stress. The postburn cardiac dysfunction
      has been mainly attributed to the reduced blood flow returned to the heart due to
      decreased blood volume caused by increased capillary permeability. Therefore,
      postburn cardiac dysfunction has been considered to be the result of burn shock.
      During the past two decades, we have performed serial studies on severe burns,
      and found that ischemic/hypoxic myocardial damage and functional impairment of
      myocardium due to activation of renin angiotensin system existing in the heart
      itself occur immediately after severe burns even before significant reduction in
      blood volume secondary to an increase of capillary permeability. Such prompt
      myocardial damage leads to cardiac deficiency, and it is also a precipitating
      factor for burn shock and ischemic/hypoxic injury of systemic tissues and organs.
      Therefore, we called it "shock heart" in our reports. The cellular and molecular
      mechanisms leading to myocardial damage were systematically investigated.
      Strategies for prevention of early postburn myocardial damage and dysfunction,
      and a new effective burn shock resuscitation regimen "volume replacement" plus
      "dynamic support" (cardiac support and myocardial protection) have been proposed
      based on our previous studies.

PMID- 19103022
TI  - [Advancement in study of inhalation injury].
AB  - Inhalation injury is a major contributor to the morbidity and mortality
      associated with serious burns. The improvement in the understanding of smoke
      inhalation injury had been obtained in the last half century in China. The models
      of steam and smoke inhalation injury had been reproduced and a series of
      experimental studies had been performed. It was found that chemical
      bronchiotracheitis, pulmonary edema and alveolar collapse (atelectasis) were the
      primary pathologic findings after inhalation injury. The second inflammatory
      response would play an important role in the development of acute respiratory
      failure. The roles of some cytokines, inflammatory cells and pulmonary
      surfactants in the development of inhalation injury had been elucidated. The
      etiologic factors and the pathophysiologic changes in inhalation injury had been
      illustrated clearly. These basic science investigations had led to the advances
      in protective strategies for the complications of inhalation injury. Now the
      morbidity and mortality of inhalation injury have decreased markedly in China.

PMID- 19103023
TI  - [Treatment of inhalation injury with high frequency ventilation].
AB  - High frequency ventilation (HFV) is a kind of lung protective ventilation
      strategy. High-frequency jet ventilation (HFJV) can decrease the water content,
      relocate interstitial fluid and accelerate lymph flow in the lung of dogs with
      smoke inhalation injury. HFJV can effectively improve breathing mechanics and gas
      exchange in dogs with smoke inhalation injury. Clinical application also proves
      that HFV is efficient in treatment of inhalation injury.

PMID- 19103024
TI  - [The present strategy and ponderation on prevention and treatment of burn sepsis
      and multiple organ dysfunction syndrome (MODS)].
AB  - Most of the major advances in the prevention and treatment of burn sepsis and
      MODS have been made within the last 20 years. Improvements have been made in
      gaining a better understanding of the pathophysiology of burn sepsis and MODS, in
      revising the definition of sepsis and MODS, and in prevention and treatment of
      burn shock. Additionally, improvements have been made in fluid resuscitation in
      patients with burn shock and in early gastrointestinal feeding to prevent
      translocation of endotoxins from the gut. Other achievements have been made in
      using recombinant human growth hormone combined with intensive insulin therapy to
      control hyperglycemia, and potassium chloride to prevent hypokalemia in order to
      accelerate protein synthesis. Additional advances include early closure and
      coverage of the burn wound, rational use of antibiotics, immunological modulation
      to combat immunological dissonance. Also, advances have been made by using early
      anticoagulation treatment to prevent coagulopathy. In prevention and treatment of
      burn sepsis and MODS, comprehensive support for all organs during the course of
      treatment is emphasized. Although the advances in burn treatment have been
      extremely encouraging over the last 50 years, burn sepsis and MODS remain the
      most common cause of mortality in the critical ill. To cope with extreme
      environmental conditions, such as armed conflict and natural disasters, research
      is needed to optimize the oral resuscitation regime, and more efficacious
      treatment strategies that are based on an indepth understanding of the
      pathogenesis of sepsis.

PMID- 19103025
TI  - [Achievements and challenge of treatment of electric burn over the past 50 years
      in China].
AB  - The electric burn is a kind of special injury, in which the injured areas are not
      big, but deep tissues and organs are often injured, resulting in higher rates of
      mortality and amputation than thermal injury. In the process of management,
      besides the treatment for systemic and pathologic changes, wound repair is also
      emphasized for restoration of function. In the past 50 years, ten thousand
      patients with electric burn were cured in our country, including hundreds of
      severe electric burn patients with extensive injury. Lots of operative regimes
      for electric burn were developed, and the scope of experimental research was
      broadening. As a result, six monographs concerning electric burns were published.
      However, clinical management of severe electric burn to give a satisfactory
      result is still difficult, therefore further indepth research is necessary,
      especially in the field of the use of artificial skin, vessels, nerves, muscular
      tendon, etc. from gene and tissue engineering to improve quality of wound repair.

PMID- 19103026
TI  - [Burn-blast combined injury].
AB  - Burn-blast combined injury is caused by two injury factors--heat and blast, which
      inflict the body at the same time or in sequence. The incidence of the combined
      injury is high either in wartime or in peacetime, and the mortality is much
      higher than that of an injury due to either one injury factor. In order to
      elucidate the mechanism, characteristics of the injury and the treatment of the
      combined injury, lots of studies were carried out both at home and abroad. The
      paper presents the data of burn-blast injury from a part of experimental studies
      and some clinical experience in the past forty years. The paper may be useful to
      medical doctors who may treat burn-blast injury in future.

PMID- 19103027
TI  - [Studies on the treatment of combined radiation-burn injury].
AB  - Combined radiation-burn injuries mainly occur under the circumstances of nuclear
      explosion, nuclear accident, nuclear terrorism, depleted uranium attack, as well
      as secondary injuries following attack on nuclear installation. Combination of
      burn and radiation injuries bring along more serious whole body damage, more
      complicated pathological mechanism and much more difficult management. Research
      progress on the pathological mechanism and medical management of several key
      links of combined injury were discussed in this paper. (1) Enhancement of early
      first aid and prevention of early death of wounded. (2) Damage and restoration of
      hemopoietic function. (3) Disturbance of immune function and prevention and
      treatment of infection (mainly on the intestinal mucosa immunity and
      enterological infection). (4) Management of burn wound. (5) The role of several
      important measures in the comprehensive treatment.

PMID- 19103028
TI  - [Researches in immunological responses after burn injury in China].
AB  - For five decades it has been recognized that severe burn injury may precipitate
      in marked alterations in immune function, resulting in life-threatening systemic
      infections, sepsis, multiple organ failure, and even death. Extensive and deep
      burns exert widespread and profound impacts on various cells and molecules of the
      immune system. The general characteristics of abnormal immune responses following
      major burns are hyperinflammatory response and hypoimmune response of innate and
      adaptive immunity. These are recognized as postburn immune dysfunction (PID). The
      stress reaction, massive necrotic tissue, shock, infection, malnutrition and
      various therapeutic procedures after burns alter the microenvironment of the
      immune cells and molecules in which they reside, and consequently result in the
      changes in immune cells and their secretions in quantity and/or activity, and
      also aberrant signal transduction in different immune cells. These events
      constitute the cellular and molecular bases in the pathogenesis of PID. The main
      clinical consequences of PID include tissue damages and increased susceptibility
      to opportunistic pathogens caused by refractory inflammation and suppressed
      adaptive immunity. In order to decrease the morbidity of these lethal
      complications, efforts to improve the immune dysfunction after burn injury have
      been made not only at the integral level of etiological factors, but also at the
      cellular and molecular levels of its mechanisms. In this review, all these above
      mentioned aspects of PID are comprehensively discussed.

PMID- 19103029
TI  - [Review and prospect of parenteral nutrition support for burn patients in China].
AB  - Parenteral nutrition support for burn injury in China began to develop in 1970s
      along with improvement in burn foundational research of burn injury and the
      marketing of parenteral nutrition solutions manufactured by Chinese amino acids
      pharmaceutical industry. Up to 1980s many kinds of parenteral nutrition products
      were used in clinical therapy, and they were proved to be effective and safe.
      Meanwhile the guide for parenteral nutrition support of China was drafted to
      ensure standardized administration. Some problems should be called for attention
      in present practice of parenteral nutrition support. First, immuno nutrients have
      been proved to possess synergistic effect on parenteral/enteral nutrition
      support. But for those critical patients in sepsis/MODS period, more attention
      should be paid to the use of immuno nutrients in time of administration and
      optimal dosage because of the complicate physiopathologic reactions. Secondly,
      the use of growth hormone has been proved to be effective for promoting healing
      in patients with burn in many cases. However, the indications of growth hormone
      should be strictly observed and the regime of a low dose and short course should
      be adopted 7 days after burn for ensuring safety. Thirdly, we should pay
      attention to the best path of giving nutrition, whether enteral or parenteral.
      Parenteral nutrition support should be adopted for critical burn patients in
      early period with intestinal dysfunction, and enteral nutrition support should be
      used when intestinal functions recover partially. For patients with burn
      hypermetabolism, the application of enteral and parenteral nutrition support is
      complimentary, and it is aptly called total nutrition.

PMID- 19103030
TI  - [Progress of burn research in metabolism and nutrition in China].
AB  - The achievements of burn metabolism and nutrition in China are briefly presented.
      Advance a new theory "Enterogenous Hypermetabolism". Develop a formula to
      calculate calorie needs in Chinese burn adults. Put forward new ideas on glucose
      absorption, neo glycogenesis, insulin resistance, and the use of hypoglycemic
      agent after burn injury. Observe the variation of plasma level of free
      aminoacids, investigate the changes and mechanisms of 26S proteasome and 19S
      regulator in skeletal muscle of burn trauma, and the clinical application and its
      mechanism of glutamine and arginine. Introduce the approach of (13)C NMR
      spectroscopy to investigate the alterations of hepatic anabolism functions in
      severely burned rats. Offer supplying the suitable dosage of vitamin A, C, E and
      microelement of zinc, copper, ferrum for burn patients. Carry out serial studies
      of early enteral and parenteral nutrition, and compare enteral nutrition with
      parenteral nutrition. Early enteral nutrition with synbiotics might be beneficial
      to the controlling of burn infection. Both glucagon like peptide-2 (GLP-2) and
      intestinal trefoil factor (ITF) exhibit protective effect on intestinal mucosa in
      minimizing injury and protecting barrier function. The choice of suitable
      opportunity to use rhGH (growth hormone) is investigated. In addition, advance
      the view points of ischemia and anoxia in metabolism, anti-inflammatory immune
      and nutrition.

PMID- 19103104
TI  - [Study on the status of metabolic syndrome in familial type 2 diabetes
      pedigrees].
AB  - OBJECTIVE: To investigate the prevalence of metabolic syndrome (MS) and its
      components in type 2 diabetes mellitus pedigrees. METHODS: A total number of 4468
      subjects (including spouses) from 715 type 2 diabetic pedigrees were selected in
      this study. Complete laboratory data including blood pressure, lipid profile and
      plasma glucose, were collected. All subjects who were not defined as diabetic
      were valued by oral glucose tolerance test. MS was diagnosed according to the
      definition proposed by the China Diabetes Society (CDS) in 2004. RESULTS: (1) The
      prevalence of MS was 23.86% in diabetic pedigrees, and subsequently increased in
      second-degree relatives, spouses, first-degree relatives and probands. (2) The
      prevalence rates of 'at least' 1 metabolic abnormality in first-degree relatives,
      second-degree relatives and spouses were 80.10%, 59.76% and 70.30%, respectively.
      (3) Ratios on non-metabolic abnormality, 1 - 2 metabolic abnormality and MS were
      19.90%, 55.02% and 25.08% in first-degree relatives, 40.24%, 50.82% and 8.94% in
      second-degree relatives, 29.70%, 53.31% and 16.99% in spouses, respectively. (4)
      Among the first-degree relatives, the common manifestation of metabolic
      abnormality was dyslipidemia for subjects aged below 40 years, and hyperglycemia
      for subjects aged over 40 years of age. (5) The prevalence of MS in first-degree
      relatives was higher in males than in females for subjects aged below 60 and it
      was higher in females than in males for subjects aged over 60. CONCLUSION: There
      was significant familial aggregation of MS found in our study. The first-degree
      relatives of type 2 diabetic patients were high risk populations, suggesting that
      early recognition and prevention were important issues to be carried out.

PMID- 19103105
TI  - [Study on the risk factors of hypertension among rural residents in mid-west
      areas of Shandong province, using the classification tree analysis methodology].
AB  - OBJECTIVE: To explore the risk factors of hypertension and risk population for
      adults aged > or = 25 in the mid-western rural areas of Shandong province and to
      provide evidence for development of intervention measure. METHODS: Subjects aged
      > or = 25 were selected by multi-stage stratified random sampling method. All
      participants were interviewed with a standard questionnaire and physically
      examined on height, weight, waist circumference, blood pressure and fasting
      plasma glucose (FPG). Classification tree analysis was employed to determine the
      risk factors of hypertension and high risk populations related to it. RESULTS:
      The major risk factors of hypertension would include age, abdominal obesity,
      overweight or obesity, family history and high blood sugar. The major populations
      at high risk would include populations as: a) being elderly, b) at middle-age but
      with: high blood sugar or with abdominal obesity/overweight, or with family
      history, c) people at middle-age but with family history and abdominal obesity.
      Through classification tree analysis, sensitivity, specificity and overall
      correct rates were 71.87%, 66.38% and 68.79%, respectively on 'learning sample'
      while 70.70%, 65.84% and 67.97% respectively on 'testing sample'. CONCLUSION:
      Efforts on both weight and blood sugar reduction were common prevention measures
      for general population. Different kinds of prevention and control measures should
      be taken according to different risk factors existed in the targeted high-risk
      population of hypertension. Community-based prevention and control for
      hypertension measures should be integrated when targeting the population at high
      risk.

PMID- 19103106
TI  - [Study on the association of predisposing genes with essential hypertension among
      Kazakhs ethnic group in Xinjiang].
AB  - OBJECTIVE: To investigate the association between M235T and G-6A polymorphism of
      AGT gene, insertion/deletion (I/D) polymorphism of ACE gene, Gly460Trp
      polymorphism of ADD1 gene, C825T polymorphism of GNB3 gene and essential
      hypertension in Xinjiang Kazakhs group as well as to identify the interactions of
      gene-gene and gene-environment. METHODS: A case-control study (n = 441) was
      performed in 241 cases and 202 controls. Polymerase chain reaction and restrict
      fragment length polymorphism (PCR-PFLP) technique were used to detect the
      genotypes polymorphism. RESULTS: Comparing the frequencies of alleles and
      genotypes, there were no statistical significances except frequency of allele of
      M235T (P = 0.0483) identified. In logistic regression analysis, there were
      significant differences in all of the loci. The 4 loci model (AGE/CHO/G-6A/ACE)
      appeared the best model in MDR analysis. CONCLUSION: Our research data showed
      that the polymorphisms of all the four genes might be associated with
      hypertension in the Kazakhs group of Xinjiang while there might be interactions
      existed in AGT, ACE, AGE and CHO.

PMID- 19103107
TI  - [Study on factors related to top 10 junk food consumption at 8 to 16 years of
      age, in Haidian District of Beijing].
AB  - OBJECTIVE: To study the current situation of ten types of junk food consumption
      (assessed by World Health Organization) among children and adolescent as well as
      the contributing factors in Haidian District, Beijing so as to provide evidence
      for developing preventive and control measures and interventions. METHODS: A
      questionnaire survey was conducted to investigate the consumption of ten types of
      junk food practices in 1019 children and adolescent aged 8-16 years in Beijing
      Haidian District. RESULTS: One month prior to the study, 97.50% of the children
      and adolescent had eaten at least one type of junk food and 15.88% of them had
      eaten all types of them. Rates on having eaten deep fried food, pickled food,
      processed meat products, biscuits, coke or alike drinks, convenience/fast food,
      canned food, dried or preserved fruit, cold and sweet food, barbecue food etc.
      appeared to be 70.43%, 60.14%, 79.72%, 64.24%, 69.63%, 78.72%, 42.16%, 51.95%,
      68.13%, 60.14% respectively. The rate on eaten more than once a day of these ten
      types were 26.95%, 36.88%, 34.84%, 32.97%, 27.40%, 28.18%, 37.91%, 26.15%,
      37.39%, 22.10% respectively. The rates for "do not like" and "dislike" these ten
      types junk food were 10.96%, 27.42%, 7.08%, 12.11%, 6.56%, 6.59%, 17.80%, 13.59%,
      3.42%, 5.19% respectively. Most of the children and adolescent ate junk food
      mainly during breakfast at home. Most of the surveyed children and adolescent did
      not have correct idea on nutrition of junk food. They received the information of
      junk food mainly from sources as advertisement on TV (67.95%), mother (9.02%),
      newspaper or magazines (6.71%). Many factors, such as individual factors
      (including physiological and psychological situations), social factors, family
      factors and the characteristics of food contributed to the eating junk food
      practices of children and adolescent. CONCLUSION: Eating junk food is a popular
      event among children and adolescent in Beijing Haidian District. Education
      strategies on nutrition should be developed and launched in order to help
      children develop their own healthy eating behaviors.

PMID- 19103109
TI  - [Field study on the change of urinary iodine levels among family members with
      iodine content of 5 - 150 microg/L in drinking water before and after non-iodized
      salt intervention].
AB  - OBJECTIVE: To compare the changes of urinary iodine levels among the family
      members with iodine content of 5 - 150 microg/L in drinking water, before and
      after non-iodized salt intervention through a field trail study. METHODS: Family
      members who routinely drank water with iodine content 5 - 150 microg/L were
      chosen to substitute non-iodized salt for their current iodized salt for 2
      months, and urine samples of the family members were collected for determination
      of iodine change before and after intervention was carried out. RESULTS: Median
      urinary iodine of school children, women with productive age and male adults
      exceeding 370 microg/L before intervention and the frequency distribution of
      urinary iodine were all above 70%. Our results revealed that iodine excess exited
      in three groups of family members. After intervention, all median urinary iodine
      level seemed to have decreased significantly, and groups with drinking water
      iodine 5.0 - 99.9 microg/L reduced to adequate or close to adequate while the
      group that drinking water iodine was 100 - 150 microg/L reached the cut-off point
      of excessive iodine level (300 microg/L). CONCLUSION: Results from your study
      posed the idea that the iodine adequate areas should be defined as the areas with
      iodine content of 5.0 - 100 microg/L in drinking water, and edible salt not be
      iodized in these areas. Areas with iodine content of 100 - 150 microg/L in
      drinking water should be classified as iodine excessive.

PMID- 19103108
TI  - [A case-control study on serum organochlorines residues, genetic polymorphisms of
      glutathione S-transferase T1 and the risks of breast cancer].
AB  - OBJECTIVE: To study the potential effect of gene-environment interaction between
      glutathione S-transferase T1 (GSTT1) and serum organochlorines residues on the
      risk of breast cancer in women, in China. METHODS: 70 newly diagnosed female
      breast cancer patients and 30 controls from September 2006 to October 2007 were
      interviewed using the same questionnaire to obtain information regarding exposure
      to those risks. Organochlorine residues level in serum was measured by gas
      chromatography (GC). Genotypes of GSTT1 polymorphisms were analyzed by multiplex
      allele-specific polymerase chain reaction (PCR). Interaction indexes (gamma) were
      calculated to determine the type of gene-environment interaction. RESULTS: After
      adjusting the confounding factors, results showed that interaction existed in
      genetic polymorphisms of GSTT1 and dichlorodiphenyltrichloroethane
      (DDT)/hexachlorocyclohexane (HCH) residues, with interaction indexes (gamma)
      value as 1.352 and 1.528. CONCLUSION: Genetic and environmental hazard factors
      had a co-effect on the development of breast cancer while genetic polymorphisms
      of GSTT1 and DDT/HCH expressed an interaction to breast cancer.

PMID- 19103110
TI  - [A case-control study on the risk factors of neural tube defects in Shanxi
      province].
AB  - OBJECTIVE: To explore the risk factors of neural tube defects (NTDs) in Shanxi
      province where the incidence of NTDs had been the highest in China. METHODS: 1:1
      matched case-control study was used. All the objects collected from hospitals
      were investigated in standardized questionnaires about susceptible risk factors
      for NTDs and were genotyped for methylenetetrahydrofolate reductase (MTHFR) C667T
      polymorphism by PCR-RFLP method. The risk factors of NTDs were analyzed by
      conditional logistic regression and by SPSS 11.5 statistical software. We also
      analyzed the univariable and multi-variables in order to independently
      investigate the MTHFR genotype and maternal periconceptional adverse factors
      influencing on NTDs. RESULTS: Comparing MTHFR gene frequency between case group
      and control group, our results showed that three genotypes were found in MTHFR
      C677T. There was significant difference between two groups at 0.01 level (chi2 =
      14.61, P = 0.001) about the three genotypes. The MTHFR T allele frequency of
      mother with NTDs (60.6%) was higher than that of the control (41.4%), and there
      was significant difference between them (chi2 = 14.59, P < 0.001). By univariate
      conditional logistic regression analysis, it was indicated that 15 factors were
      correlated with NTDs (P < 0.05) in the level alpha = 0.05. By multi-variables
      conditional logistic regression analysis, four factors were connected to NTDs:
      frequency of pregnancy (OR = 2.87, 95%CI: 1.28 - 6.44), contacting chemical
      combination in early pregnancy (OR = 16.18, 95%CI: 1.18 - 221.59), frequent
      taking of germinated potato (OR = 4.66, 95%CI: 1.78 - 12.17) and MTHFR C677T
      mutation (OR = 2.13, 95%CI: 1.08 - 4.21). CONCLUSION: Factors as 'frequency of
      pregnancy', 'history of contacting chemicals', 'taking germinated potatoes in
      early pregnancy', as well as 'MTHFR C677T mutation' in mothers were important
      risk factors affecting the occurrence of NTDs in Shanxi province.

PMID- 19103111
TI  - [Study on traffic induced injuries in children aged 0-17 years in Jiangxi
      province].
AB  - OBJECTIVE: To explore the morbidity, mortality, and disease burden of traffic
      injury in children aged 0-17 years so as to develop a related strategy on
      prevention. METHODS: 100,000 households were selected by PPS sampling method in
      Jiangxi province. All children aged 0-17 years in selected households were
      interviewed by trained interviewers using a standardized 'traffic injury
      questionnaire'. RESULTS: The overall mortality and fatality rates of traffic
      injury were 10.17/100,000 and 1.36% respectively while the traffic injury
      morbidity in children of 0-17 years old was 7.40 per thousand. Morbidity in males
      was 8.29 per thousand compared to 6.26 per thousand in females. Severe cases
      accounted for 1.79 per thousand of the total but those living in urban area
      appeared to be 0.93 per thousand compared to 1.88 per thousand in the rural area,
      with statistical significance. Pedestrian and cyclists related injuries accounted
      for 80.48% of all the injured children. The average medical cost per case was
      1369.57 Yuan with an average of 3.63 days of hospitalization. The average days of
      missing school/working was 8.79. CONCLUSION: The morbidity and mortality among
      male children were higher than those among female children. The morbidity of
      severe traffic injury cases in children living in rural area was higher than that
      of children living in urban area. The disease burden of traffic injury in Jiangxi
      province was heavy and the development of relative intervention strategy seemed
      urgent in Jiangxi province.

PMID- 19103112
TI  - [A follow-up study on the degree of satisfaction regarding environment, life
      style and the coming Olympic events in the inhabitants living in the typical
      communities of Beijing].
AB  - OBJECTIVE: To measure the degree of satisfaction on various environmental and
      health components and to discuss the impact of Olympic Games among the residents
      so as to make relative policy suggestions. METHODS: In 2006, permanent residents
      over 15 years old lived in the Asian Games Village Community (where the 29th
      Olympic Games to be held) were selected to conduct a household's survey, while
      1610 valid questionnaires were collected. The questionnaire included demographic
      information, degrees of satisfaction on various health-related environmental
      components, living condition and on Olympic events. RESULTS: The top 4 aspects
      with the highest satisfaction rates were "overall rates of satisfaction on
      current life" "green space", "housing conditions" and "water quality", which were
      50.43%, 48.59%, 38.95%, 37.08%, respectively. Residents' satisfaction on "impact
      of hosting the Olympic Games on China's international image", "China's economic
      development level", "living conditions" and "personal life" were 65.53%, 56.09%,
      47.27%, 46.40%, respectively. Data from partial correlation analysis showed that
      the total scores of satisfaction on environment and life had positive correlation
      with the total scores of Olympic satisfaction (P < 0.05). The satisfaction degree
      on Olympic event through factor analysis showed that 10 entries of the Olympic
      impact could be reflected by two factors--the influence of image to the nation
      and impact on personal income. Logistic regression showed that the impact of
      Olympic Games on personal income, the impact of Olympic Games on the image of the
      nation and standard of living, gender, education level were independent
      influencing factors of the total scores of environment and life satisfaction (P <
      0.05). CONCLUSION: Other than "green space", most of health-related environment
      components of Beijing had low degree of satisfaction among inhabitants from the
      'typical' communities in Beijing. However, residents had a higher degree of
      satisfaction on the impact of the Olympic Games to the country's image, the
      country's economic development level, the environment and personal standard of
      living.

PMID- 19103114
TI  - [Study on the prevalence rate and immunity of hepatitis B virus infection among
      urban adults aged over 20 years in Wuxi, Jiangsu province].
AB  - OBJECTIVE: To study the relationship on the prevalence rate of hepatitis B virus
      (HBV) infection and hepatitis B vaccination in urban citizens aged over 20 years
      old which would led to the development of strategies on HBV control. METHODS: A
      total of 3744 subjects from general population were randomly selected in this
      study. Both ELISA and radio immunoassay were used to test five items of HBV
      infection, including HBsAg, anti-HBs, HBeAg, anti-HBe and anti-HBc. RESULTS: The
      overall standardized infection rate of HBV was 51.7%, and HBsAg, anti-HBs, HBeAg,
      anti-HBe and anti-HBc were 4.5%, 48.5%, 0.3%, 3.5% and 51.4%, respectively. The
      two lowest HBsAg positive rates were found in the groups under 30 years old
      (2.9%) and students (2.6%). Anti-HBc rate among men was significantly higher than
      seen in women (P < 0.05), and showing a trend of increase with age (chi2 for
      trend = 256.2, P < 0.001). The standardized rates of HB vaccination in this
      population was 17.6% and decreasing rapidly with age (P < 0.05). People who had
      been vaccinated had both lower rates of HBsAg and HBV infection but higher rate
      of anti-HBs than those who had not (P < 0.05). CONCLUSION: HB vaccination in
      adults showed a reducing rate of HBV infection in the general population.
      Together with the enhancement of expanded program on immunization towards HB
      vaccination in neonates, much attention should be paid to HB vaccination in
      adults.

PMID- 19103115
TI  - [Study on the threshold of HIV-1 drug resistance in Hunan province].
AB  - OBJECTIVE: To survey the prevalence of HIV-1 drug resistance in patients newly
      diagnosed as HIV positive and who were younger than 25 years of age but had not
      received treatment with antiretroviral treatment (ART) in Hunan province.
      METHODS: Serum specimens of HIV infected individuals were collected and HIV-1 pol
      genetic mutations associated with drug resistance were identified with PCR and
      interpreted with Stanford HIV Drug Resistance Database. RESULTS: A total number
      of 69 patients whose HIV sequences were amplified successfully with 2 (2.9%)
      specimens appeared mutations associated with HIV-1 drug resistance in the reverse
      transcriptase region, including one as V75M and the other one as K103N and V181C.
      Data showed that the prevalence of drug resistance in Hunan was 2.9%. CONCLUSION:
      The first line regiments of national ART seemed still effective. Most of the AIDS
      patients did not need to be tested on drug resistance status before starting ART.
      However, it is important to start HIV drug resistance surveillance in no time.

PMID- 19103116
TI  - [Genotype analysis of enterovirus type 71 detected from patients with hand-foot
      mouth disease in Shenzhen].
AB  - OBJECTIVE: To carry out genotype analysis of enterovirus type 71, detected from
      hand-foot-mouth disease patients in Shenzhen in 2004. METHODS: All samples were
      tested by reverse transcription-polymerase chain reaction (RT-PCR) using EV71
      specific primer. The VP1 and VP4 of EV71 were cloned and sequenced. A
      phylogenetic tree was constructed by comparing the sequences with genogroups A, B
      and C genotypes using TreeView and PHYLIP software (3.6b). RESULTS: The VP1
      nucleotide sequence of 4 strains isolated from Shenzhen shared 87.8% - 92.0%
      identity with genogroup C, while the homogeneity of the VP4 nucleotide sequence
      was between 85.9% - 87.4%. The homogeneity of the VP1 nucleotide sequence with
      genotypes A and B was between 81.9% - 84.2% and was 80.6% - 85.0% with VP4. Among
      the 4 strains, the homogeneity of the VP1 nucleotide sequence was between 94.1% -
      99.8% and was 100% with VP4 which formed a small group and could denominate EV71
      genetype C4. CONCLUSION: Similar results were obtained from phylogenetic analysis
      of EV71 based on VP1 and VP4 nucleotide sequence. The four EV71 strains causing
      epidemic in Shenzhen could be named as C4 subgroups.

PMID- 19103117
TI  - [Research on the selective kinetics of HIV-1 nucleoside reverse transcriptase
      inhibitor drug resistance-associated mutations among 4 AIDS patients receiving
      highly active antiretroviral therapy].
AB  - OBJECTIVE: To elucidate the molecular evolutional characteristics of HIV-1
      nucleoside reverse transcriptase inhibitor (NRTI) drug resistance-associated
      mutations in patients with AIDS receiving highly active antiretroviral therapy.
      METHODS: We selected 4 AIDS patients receiving highly active antiretroviral
      therapy (HAART) with good adherence under a HIV-1 drug resistance cohort from a
      rural region in central China. Those people carried susceptible virus at the
      beginning of treatment and gradually came to produce virus resistant to NRTIs
      during the process of antiretroviral therapy (ART). Reverse transcriptase (RT)
      genes from each patient's peripheral blood samples (from 3 to 33 months after
      withdrawal) were cloned and sequenced in succession. RESULTS: We sequenced a
      total number of 855 clones and obtained the HIV-1 NRTI drug resistance-associated
      mutations patterns of the 4 patients. Typical resistance mutations of thymidine
      analogue mutations (TAMs) pattern 1, such as L210W, T215Y and M41L, were
      generated in patient 'A'. TAMs pattern 2, including D67N, K70R and K219Q
      mutations, was discovered in patient 'B'. Interestingly, in patient 'C', some
      clones comprising not only TAMs pattern 1 mutations (T215Y) but also TAMs pattern
      2 mutations (K70R, D67N). CONCLUSION: The four patients show different pathways
      on HIV-1 NRTI drug resistance-associated mutations, including TAMs pattern 1,
      TAMs pattern 2 and the fusion pattern of TAMs-1 & TAMs-2. We also noticed that
      the tendency of gradual accumulation was obvious and those mutations detected
      earlier tended to be the predominant strains.

PMID- 19103118
TI  - [Establishment and application of a standard IS6110-RFLP method in the study of
      molecular genotyping analysis on Mycobacterium tuberculosis].
AB  - OBJECTIVE: To develop a standardized IS6110-restriction fragment length
      polymorphism (RFLP) method, used for evaluating the capacity of genotyping.
      METHODS: IS6110-RFLP of 78 Mycobacterium (M.) tuberculosis strains were studied
      by bio-molecular techniques including DNA isolation, PCR, restriction
      endonuclease enzyme analysis, southern blotting, agarose gel electrophoresis,
      together with data analysis by software Gel-Pro analyzer 3.1 and BioNumerics
      (Version 5.0). RESULTS: IS6110-RFLP method was established and standardized
      successfully, including DNA isolation, PCR, restriction endonuclease enzyme
      analysis, southern blotting, agarose gel electrophoresis and usage of the
      analysis software with standard parameters. By this method, 78 M. tuberculosis
      isolates were classified into 75 genotypes which belonged to 11 different
      clusters. Of all the isolates, 66.7% (52/78) belonged to a main cluster.
      CONCLUSION: Standard IS6110-RFLP method was established successfully. This method
      had powerful capacity for genotyping and strain level identification and could be
      used for the surveillance on pathogens of M. tuberculosis in China.

PMID- 19103119
TI  - [Detection of Haemophilus influenzae by multiplex polymerase chain reaction
      method].
AB  - OBJECTIVE: To develop a rapid method for detecting Haemophilus influenzae by
      multiplex polymerase chain reaction (M-PCR). METHODS: Primers (Hi) were designed
      for amplification of p6 gene coding P6 protein of Haemophilus influenzae, which
      was used to identify Haemophilus influenzae species. Primers (Hi-cap) were
      designed for amplification of bexA gene which coding capsular polysaccharide
      (cap) synthesis was used for detecting whether Haemophilus influenzae isolates
      possess bexA gene relating to cap synthesis. Twelve primers (Hia-Hif) were
      designed for amplification of cap synthesis gene to identify the cap-type of
      Haemophilus influenzae. Other relative enteric pathogenic bacteria were amplified
      by M-PCR to serve as controls. 200 strains isolated from patients were
      identified. Results from M-PCR were compared to two methods including V and X
      factors grow requirement test and standard slide agglutination serotyping (SAST).
      RESULTS: The results indicated that the M-PCR assay was high specificity and
      sensitivity and might be valuable for differential diagnosis of Haemophilus
      influenzae. The sensitivity of detection was 0.935 pg. 189 strains out of the 200
      belonged to Haemophilus influenzae isolates, and one isolate was cap-type f. An
      agreement results were seen among the V and X factors grow requirement test, SAST
      and M-PCR methods. CONCLUSION: M-PCR method showed satisfactory sensitivity,
      specificity and stability for detecting and identifying Haemophilus influenzae,
      and could be used in clinic diagnosis, surveillance and rapid diagnosis for
      plague of Haemophilus influenzae.

PMID- 19103120
TI  - [Comparison of the kinesis of immune responses in mice vaccinated by different
      kinds of recombinant hepatitis B vaccines].
AB  - OBJECTIVE: To evaluate the kinesis of cellular and humoral immune responses to
      different kinds of recombinant hepatitis B(rHB) vaccines in the immunized mice.
      METHODS: At serial time points, the levels of IFN-gamma and IL-2 secreted by
      spleens mononuclear cells (MNC) of the vaccinated mice were detected by enzyme
      linked immunospot methods (ELISPOT) after stimulation in vitro with HBsAg MHC
      class I peptide S28-39 or HBsAg. The lymphocytotoxicity of the immunized mice
      were also detected (CTL) by a specific lysis assay and the levels of anti-HBs
      were measured by the Abbott IMX kit. RESULTS: The peak values of IFN-gamma and IL
      2 in vaccinated mice were detected by ELISPOT, 10 - 14 days after immunization.
      The CTL and the level of IFN-gamma induced by rHB vaccine derived from yeast
      cells (Hansenula polymorpha) (rHP vaccine) were significantly higher than the
      other two vaccines (P < 0.05). The maximum lysis of CTL appeared in the
      vaccinated mice on day 10 after immunization, with the percentage of 39.8%. The
      levels of IL-2 induced by rHP vaccine were significantly higher than the other
      two vaccines (P < 0.05). However, the IL-2 levels in the rSC (saccharomyces
      cerevisiae) vaccine group were higher as compared with the rCHO vaccine group at
      day 7 and day 14 (7 d t = 4.595, P = 0.001 < 0.05; 14 d t = 5.721, P = 0.000 <
      0.05) after immunization. The cellular immune response to the rHP vaccine was the
      strongest while it was the lowest to the rCHO vaccine at day 7 after
      immunization. The sero-positive rates and the titers of anti-HBs in the
      vaccinated mice increased with time after vaccination. The titers of anti-HBs in
      the rCHO vaccine group at day 7 were similar to the rSC vaccine group, but
      significantly higher than that of the rHP vaccine group (P = 0.044 < 0.05). The
      anti-HBs titers of the rCHO vaccine group at day 14 were significantly higher as
      compared to the rSC (P = 0.012 < 0.05) and rHP (P = 0.009 < 0.05) vaccine groups.
      CONCLUSION: The immune responses induced by the three kinds of rHB vaccines were
      different in their patterns and levels. According to the intensity of early
      cellular immune response, the two yeast HB vaccines were superior to the rCHO
      vaccine, especially to the rHP vaccine. In contrast, the rCHO vaccine induced
      early seroconversion and high levels of anti-HBs.

PMID- 19103121
TI  - [Detection and identification of seven clinical common pathogenic bacteria by
      oligonucleotide microarray].
AB  - OBJECTIVE: Using 16S rDNA and 23S rDNA genes as the target sequences to develop a
      system based on oligonucleotide microarray and to detect the seven clinical
      pathogenic bacteria, commonly seen. METHODS: Double polymerase chain reaction
      (PCR) was applied to amplify the segments of 16S rDNA and 23S rDNA genes of the
      target bacteria. An oligonucleotide microarray was constructed to simultaneously
      detect EHEC O157:H7, Vibrio parahaemolyticus, Salmonella sp., Vibrio cholerae,
      Listeria monocytogenes, Campylobacter jejuni and Shigella sp. Specificity,
      sensitivity and reproducibility of the microarray during detection were checked.
      And then microarray was used to detect the microbes in stool specimens of 81
      patients with diarrhea and vomiting. RESULTS: The double PCR method could
      simultaneously amplify the target sequences of 16S rDNA and 23S rDNA genes of the
      seven pathogens. The sensitivity of the developed oligonucleotide microarray
      could reach 10(3) cfu/ml but no positive results were presented for non-targeted
      bacteria. The coefficients of differentiation in one lot or among different lots
      of the microarray slices were 3.89% - 5.81%. The positive detection rate of the
      stool specimens by oligonucleotide microarray was 39.5% (32/81), with a
      coincidence of 96.3% (78/81) for the patients and another coincidence of 96.8%
      (31/32) for bacterial genus or species identification, when comparing to the
      results by routine bacteriological examinations. CONCLUSION: The established
      assay in this study based on oligonucleotide microarray to detect the seven
      pathogenic bacteria has many advantages such as convenient, rapid, accurate,
      stable and high flux, which is suitable for clinical specimen examination and
      epidemiological field investigation.

PMID- 19103122
TI  - [Analysis on the level of exposure and the cluster of risk factors to stroke for
      patients with non valvular atrial fibrillation].
AB  - OBJECTIVE: To analyze the level of exposure and cluster of risk factors to stroke
      for patients with non valvular atrial fibrillation. METHODS: A questionnaire
      survey was conducted among 583 patients with non valvular atrial fibrillation,
      randomly selected from 8 general hospitals and 7 community health service centers
      located in the 8 districts in Beijing city in 2006. RESULTS: 133 patients
      attacked stroke and the prevalence of stroke in the total 583 patients was 22.8%.
      78 patients attacked stroke after being diagnosed as atrial fibrillation with the
      prevalence related to atrial fibrillation as 14.3%. The levels of exposure
      related to age, duration of atrial fibrillation, histories of hypertension,
      diabetes and dyslipidemia were significantly different between stroke and non
      stroke patients (P < 0.05). Data from multiple variables logistic regression
      analysis showed that age, duration of atrial fibrillation, history of
      dyslipidemia and history of diabetes increased the risk of stroke with odds ratio
      as 1.06, 2.08, 1.82, 1.79 respectively (95%CI was not including 1). The risk of
      stroke among those having 3 or 4 risk factors was 4.36 and 4.51 times of those
      without risk factor after adjusting for age, sex and duration of atrial
      fibrillation. CONCLUSION: Age, duration of atrial fibrillation, history of
      dyslipidemia and history of diabetes were the main risk factors related to stroke
      and the clustering of risk factors would further increase the risk. It is
      important to control blood pressure, blood surge and lipid besides therapy of
      anticoagulation or antiplatelet for patients with nonvalvular atrial
      fibrillation.

PMID- 19103123
TI  - [Using satisfaction questionnaire status version (DTSQs) to study on the
      reliability, construct validity and responsiveness of diabetes treatment among
      Chinese diabetic outpatients].
AB  - OBJECTIVE: Using 'diabetes treatment satisfaction questionnaire status version
      (DTSQs)' to evaluate the reliability, validity and responsiveness, among Chinese
      type 2 diabetes mellitus (T2DM) outpatients. METHODS: A cross-sectional study was
      carried out in 749 T2DM outpatients from seven hospitals in Guangzhou and
      Shanghai, China. The DTSQs was self-administered by patients, under the help from
      interviewers for those having difficulties in reading. Split-half reliability
      correlation coefficient, Cronbach alpha and Spearman' were used to test the
      reliability. Exploratory factor analysis (EFA) and confirmatory factor analysis
      (CFA) were employed separately to examine the construct validity of the scale.
      The responsiveness of the scale was appraised by the multiple analysis of
      covariance (MANCOVA). RESULTS: The split-half correlation coefficient was 0.807
      and the Cronbach alpha was 0.717 of the six items on satisfaction of treatment.
      The three factors extracted by EFA explained 67.656% of the overall variance. The
      relative chi2 was 4.95 and DK was 0.18 in the goodness of test by CFA. The vector
      of treatment satisfaction, perceived hyperglycemia and hypoglycemia were
      different in males versus females and in poor versus good blood glucose
      controlled groups. The DTSQs showed good reliability and validity among T2DM
      outpatients. CONCLUSION: DTSQs was applicable to Chinese T2DM patients.

PMID- 19103124
TI  - [Scan statistic theory and its application in spatial epidemiology].
AB  - To introduce the basic concept of scan statistic, its computation method and
      application in the area of spatial epidemiology. Retrospective space-time
      permutation statistics for evaluating the clustering of disease monitoring
      program is illustrated, using data on recent acute onset of cardiovascular
      disease in Hangzhou, China. Calculations were performed with SaTScan Version
      7.0.3. With 999 Monte Carlo replications, the program took 5 seconds to run on a
      100-MHz Pentium PC. The geographical surveillance program on acute onset clusters
      of cardiovascular disease, data which showed statistical significance, would
      include: a) from January 1, 1997 to February 28, 2007 in Qiantan township, Jiande
      county (P = 0.001); b) highly significant between January 1, 1997 and February
      28, 1999 for Lushan street, Lingqiao township in Fuyang county (P = 0.003); c)
      between March 1, 2001 and February 29, 2004 for Dayuan town, Xinyi town,
      Shouxiang town in Fuyang (P = 0.004); d) between March 1, 2004 and Feb 28, 2006
      for Chengzhan street, Ziyang street, Hubin street, Qinbo street, Xiaoying street,
      Wangjiang street, Chaoming street, Changqing street, Wulin street, Tianshui
      street, Wenhui street and Shiqiao street in Hangzhou (P = 0.005), respectively.
      The retrospective space-time permutation statistics seems useful as a screening
      tool for identifying the cluster of disease. Scan statistics are practical and
      effective method for deciding which cluster alarms would merit further
      investigation and which clusters are probably chance occurrences in the study of
      spatial epidemiology.

PMID- 19103126
TI  - [Data analysis from surveys using complex sampling methods].
AB  - To present statistical methods on appropriate data analysis from complex surveys
      and errors arising from ignorance of weights or design of samples. We took
      Chinese National Nutrition and Health Survey in 2002 as an example to analyze the
      prevalence of hypertension among population aged 15 and over. We used four
      combinations of analyses, including with or without weighting or considering
      sample designs. If weights is omitted, it would result in biased prevalence
      estimates and also influence the estimates of standard errors. While omitting
      sample designs would result in underestimating the standard error estimates and
      then testing the false positive hypothesis. Through appropriate analysis, we
      found Chinese people in large-sized cities had the highest prevalence of
      hypertension (28.77%, 95%CI: 25.69% - 31.84%) while people in the poorest rural
      area having the lowest prevalence of hypertension (14.21%, 95%CI: 12.64% -
      15.79%). The prevalence of hypertension among people in small and medium-sized
      cities and other rural areas ranged from 20.48% to 24.37% with statistically
      insignificant difference. It is necessary to use appropriate methods to analyze
      data from complex surveys.

PMID- 19103128
TI  - [Molecular epidemiological research on human adenovirus].

PMID- 19103129
TI  - [A review on the advancement and application of group A Streptococcus
      genotyping].

PMID- 19103130
TI  - [Infection of sapoviruses children hospitalized with acute gastroenteritis in
      Lanzhou 2003--2007].

PMID- 19103131
TI  - [Analysis on the prevalence and antibiotic resistance of Moraxella catarrhalis in
      children with lower respiratory tract infection in Suzhou].

PMID- 19103132
TI  - [Epidemiological characteristics of viral respiratory tract infections in
      children in Hangzhou].

PMID- 19103133
TI  - [Clinical analysis of 99 patients with hand-foot-mouth disease].

PMID- 19103136
TI  - Imaging in intestinal ischemic disorders.
AB  - Intestinal ischemia and infarction are a heterogeneous group of diseases that
      have as their unifying theme hypoxia of the small bowel or colon. The incidence
      of bowel ischemia and infarction is on the rise for several reasons: the aging of
      the population, the ability of intensive care units to salvage critically ill
      patients, and heightened clinical awareness of these disorders. Improvements in
      diagnostic imaging techniques have greatly contributed to the earlier diagnosis
      of intestinal ischemia, which can have a positive influence on patient outcomes.
      In this article, role of radiology in the detection, differential diagnosis, and
      management of patients who have intestinal ischemia and infarction is discussed.

PMID- 19103134
TI  - Continuous positive airway pressure devices for the treatment of obstructive
      sleep apnoea-hypopnoea syndrome: a systematic review and economic analysis.
AB  - OBJECTIVES: To determine the clinical effectiveness, safety and cost
      effectiveness of continuous positive airway pressure (CPAP) devices for the
      treatment of obstructive apnoea-hypopnoea syndrome (OSAHS), compared with the
      best supportive care, placebo and dental devices. DATA SOURCES: The main search
      was of fifteen electronic databases, including MEDLINE, EMBASE and the Cochrane
      Library, up to November 2006. REVIEW METHODS: Randomised controlled trials (RCTs)
      comparing CPAP with best supportive/usual care, placebo, and dental devices in
      adults with a diagnosis of OSAHS were included. The primary outcomes of interest
      were subjective daytime sleepiness assessed by the Epworth Sleepiness Scale (ESS)
      and objective sleepiness assessed by the Maintenance of Wakefulness Test (MWT)
      and the Multiple Sleep Latency Test (MSLT). A new economic model was developed to
      assess incremental cost per quality-adjusted life-year (QALY). The cost
      effectiveness of CPAP was compared with that of the use of dental devices and
      conservative management. The costs and QALYs were compared over a lifetime time
      horizon. Effectiveness was based on the RCT evidence on sleepiness symptoms
      (ESS), which was 'mapped' to utilities using individual patient data from a
      subset of studies. Utilities were expressed on the basis of generic HRQoL
      instruments [the EQ-5D (EuroQoL-5 Dimensions) in the base-case analysis]. The
      base-case analysis focused on a male aged 50. A series of subgroup and scenario
      analyses were also undertaken. RESULTS: The searches yielded 6325 citations, from
      which 48 relevant clinical effectiveness studies were identified, 29 of these
      providing data on daytime sleepiness. The majority of the included RCTs did not
      report using an adequate method of allocation concealment or use an intention-to
      treat analysis. Only the studies using a sham CPAP comparator were double
      blinded. There was a statistically significant benefit with CPAP compared with
      control (placebo and conservative treatment/usual care) on the ESS [mean
      difference (MD) -2.7 points, 95% CI -3.45 to -1.96]. However, there was
      statistical heterogeneity, which was reduced when trials were subgrouped by
      severity of disease. There was also a significant benefit with CPAP compared with
      usual care on the MWT. There was a non-statistically significant difference
      between CPAP and dental devices (six trials) in the impact on daytime sleepiness
      (ESS) among a population with moderate symptom severity at baseline (MD -0.9, 95%
      CI -2.1 to 0.4). A review of five studies evaluating the cost-effectiveness of
      CPAP was undertaken. All existing cost-effectiveness studies had limitations;
      therefore a new economic model was developed, based on which it was found that,
      on average, CPAP was associated with higher costs and benefits than dental
      devices or conservative management. The incremental cost per QALY gained of CPAP
      was below 20,000 pounds in the base-case analysis and most alternative scenarios.
      There was a high probability of CPAP being more cost-effective than dental
      devices and conservative management for a cost-effectiveness threshold of 20,000
      pounds per QALY gained. CONCLUSIONS: CPAP is an effective and cost-effective
      treatment for OSAHS compared with conservative/usual care and placebo in
      populations with moderate to severe daytime sleepiness, and there may be benefits
      when the disease is mild. Dental devices may be a treatment option in moderate
      disease but some uncertainty remains. Further research would be potentially
      valuable, particularly investigation of the effectiveness of CPAP for populations
      with mild sleepiness and further trials comparing CPAP with dental devices.

PMID- 19103137
TI  - The etiology and pathogenesis of vascular disorders of the intestine.
AB  - Intestinal ischemia includes all the conditions in which the blood supply to the
      gastrointestinal tract is not adequate to its metabolic demand. Several ischemic
      intestinal disorders differ in clinical presentation (acute versus chronic),
      etiology (occlusive versus nonocclusive), pathophysiology (arterial or venous),
      severity (mucosal versus transmural necrosis), and location (small bowel versus
      large bowel). Atherosclerosis, thromboembolic disease, hypoperfusion states, and
      hypercoagulable disorders are the most common causes. Reperfusion, oxygen-derived
      free radicals, and eicosanoids contribute to the pathogenesis of bowel injury and
      the systemic response that occur after ischemia. The diagnosis and treatment of
      intestinal ischemia are still challenging despite the advances of radiology,
      intensive care, and surgery. This article reviews the latest data about etiology
      and pathophysiology of bowel ischemia to explain the bases of diagnosis and
      treatment of this condition.

PMID- 19103138
TI  - Clinical symptoms of intestinal vascular disorders.
AB  - Despite advances made in the diagnostic and therapeutic field, acute intestinal
      ischemia remains a highly lethal condition. This is related to the variability of
      symptoms and the absence of typical laboratory alterations in early stage.

PMID- 19103139
TI  - Small bowel vascular disorders from arterial etiology and impaired venous
      drainage.
AB  - Intestinal ischemia of the small bowel represents an important diagnostic
      question to answer in an emergency. Although some findings could be appreciated
      with basic imaging methods, the MDCT as a modern noninvasive imaging method could
      be effective in evaluating intestinal disease caused by superior mesenteric
      artery or vein occlusion and making a diagnosis of ischemia from low-flow states.
      Looking at the features of the parietal layers with knowledge of the pathologic
      mechanism underlying the changes from the "normality" could be helpful in making
      a correct, prompt, and effective diagnosis of intestinal ischemia or disease from
      impaired venous drainage.

PMID- 19103140
TI  - Imaging of ischemic colitis.
AB  - Ischemic colitis accounts for more than half of all cases of gastrointestinal
      ischemia and constitutes between 1 per 2000 and 3 per 1000 acute hospital
      admission. It typically affects elderly patients, being a frequent cause of
      rectal bleeding, abdominal pain, and diarrhea. This article describes the
      epidemiology, physiology, and pathology of this underdiagnosed condition; reviews
      the clinical patterns of this disease, which constitute a key diagnostic point in
      patients who have a thickening of the colonic wall; and describes the ultrasound
      (US) and CT findings, pitfalls, and differential diagnoses of ischemic colitis.
      The value and limitations of US and CT at the different diagnostic stages is
      discussed.

PMID- 19103141
TI  - Ischemia and infarction of the intestine related to obstruction.
AB  - In the acute obstructive syndrome, beyond the evaluation of the morphologic
      findings of the intestine (e.g. dilation, air-fluid level, whirl sign, transition
      point), it is important to consider the pathophysiology of the bowel wall in
      order to better estimate the status of viability, the degree of the obstruction
      and the presence of the intestinal ischemic complications or infarction: the
      intestine is a dynamic system and the same pathological condition can appear in
      different forms, depending on the stage of disease. MDCT examination could be of
      help in differentiating various type and degree of disease of the intestinal
      ischemia correlated to obstruction.

PMID- 19103142
TI  - Differential diagnosis of small bowel ischemia.
AB  - This article presents the differential diagnosis for small bowel ischemia.
      Clinical presentation of small bowel ischemia is variable, presenting with a
      myriad of specific or nonspecific clinical and laboratory findings. The imaging
      findings associated with small bowel ischemia are variable and combinations of
      findings may be necessary for definitive diagnosis. More specific imaging
      findings in patients with acute small intestine ischemia include bowel wall gas,
      mesenteric vessel occlusion, mesenteric venous gas, portal venous gas, or absence
      of bowel wall enhancement. Less specific imaging findings include small bowel
      wall thickening, mesenteric stranding, and mesenteric fluid. Further complicating
      the issue, several small intestinal disease processes may mimic ischemia both
      clinically and radiographically. These alternate diagnoses include infectious,
      inflammatory, and infiltrative processes.

PMID- 19103143
TI  - beta-Galactosidase activity assay using far-red-shifted fluorescent substrate
      DDAOG.
AB  - beta-Galactosidase (beta-gal) is commonly used as a reporter gene in biological
      research, and a wide variety of substrates have been developed to assay its
      activity. One substrate, 9H-(1,3-dichloro-9,9-dimethylacridin-2-one-7-yl) beta-d
      galactopyranoside (DDAOG), can be cleaved by beta-gal to produce 7-hydroxy-9H(I,3
      dichloro-9,9-dimethylacridin-2-one) (DDAO). On excitation, DDAO generates a far
      red-shifted fluorescent signal. Using this substrate, we developed a beta-gal
      activity assay method. The DDAO signal was stable for at least 18h. The signal
      intensity was linearly related to both the enzyme amount and substrate
      concentration. An optimized buffer for the beta-gal/DDAOG assay was also
      formulated. When compared with the colorimetric substrate o-nitrophenyl-beta-d
      galactopyranoside (ONPG), the signal-to-background ratio of the DDAOG method was
      approximately 12-fold higher. The beta-gal/DDAOG assay method was also tested in
      transiently transfected cells employing both pharmacologically and genetically
      inducible gene expression systems. The ability to detect signal induction is
      comparable to a similar assay using luciferase as the signal generating moiety.
      The beta-gal/DDAOG assay method should provide a fluorescent reporter assay
      system for the wide variety of beta-gal systems currently in use.

PMID- 19103144
TI  - Drug-target identification from total cellular lysate by drug-induced
      conformational changes.
AB  - Identification of drug targets is a key step in the development of novel
      pharmaceuticals. To this end, chemical probes or affinity matrices are often
      used, requiring substantial structure-activity relationship (SAR) studies. Here
      we report on the development of a novel technique for drug-target identification
      from total cellular lysate conducted independently of SAR information. This
      technique relies on binding of a drug to its target inducing a conformational
      change in target protein, thereby altering its susceptibility to proteolysis and
      resulting in specific degradation in some cases or in protection of target
      protein in others. As proof of concept, three drugs with identified targets were
      used. First, incubation of cellular lysates with okadaic acid elicited a specific
      protective effect on its target, protein phosphatase 2A catalytic subunit.
      Second, specific protection from exogenous protease of FKBP12 by FK506 and Hsp90
      fragments by radicicol were observed. We then used the method to validate the
      targets of UCS15A, an Src signaling inhibitor. UCS15A induced proteolysis of a
      number of proteins, one of which was identified as Sam68. These studies suggest
      that the technology may be generally useful for identification and validation of
      drug targets.

PMID- 19103145
TI  - NUTS and BOLTS: applications of fluorescence-detected sedimentation.
AB  - Analytical ultracentrifugation is a widely used method for characterizing the
      solution behavior of macromolecules. However, the two commonly used detectors,
      absorbance and interference, impose some fundamental restrictions on the
      concentrations and complexity of the solutions that can be analyzed. The recent
      addition of a fluorescence detector for the XL-I analytical ultracentrifuge (AU
      FDS) enables two different types of sedimentation experiments. First, the AU-FDS
      can detect picomolar concentrations of labeled solutes, allowing the
      characterization of very dilute solutions of macromolecules, applications we call
      normal use tracer sedimentation (NUTS). The great sensitivity of NUTS analysis
      allows the characterization of small quantities of materials and high-affinity
      interactions. Second, the AU-FDS allows characterization of trace quantities of
      labeled molecules in solutions containing high concentrations and complex
      mixtures of unlabeled molecules, applications we call biological on-line tracer
      sedimentation (BOLTS). The discrimination of BOLTS enables the size distribution
      of a labeled macromolecule to be determined in biological milieus such as cell
      lysates and serum. Examples that embody features of both NUTS and BOLTS
      applications are presented along with our observations on these applications.

PMID- 19103146
TI  - Determination of viable mammalian cells by luminol chemiluminescence using
      microperoxidase.
AB  - Chemiluminescent assay for menadione-catalyzed H(2)O(2) production by mammalian
      cells was modified by luminol chemiluminescence with microperoxidase instead of
      peroxyoxalate chemiluminescence with carcinogenic fluorescent materials. Luminol
      can be used as a common chemiluminescent reagent for the determination of viable
      mammalian cells and bacteria.

PMID- 19103147
TI  - Cytochrome P450 1D1: a novel CYP1A-related gene that is not transcriptionally
      activated by PCB126 or TCDD.
AB  - Enzymes in the cytochrome P450 1 family oxidize many common environmental
      toxicants. We identified a new CYP1, termed CYP1D1, in zebrafish.
      Phylogenetically, CYP1D1 is paralogous to CYP1A and the two share 45% amino acid
      identity and similar gene structure. In adult zebrafish, CYP1D1 is most highly
      expressed in liver and is relatively highly expressed in brain. CYP1D1 transcript
      levels were higher at 9h post-fertilization than at later developmental times.
      Treatment of zebrafish with potent aryl hydrocarbon receptor (AHR) agonists
      (3,3',4,4',5-pentachlorobiphenyl or 2,3,7,8-tetrachlorodibenzo-p-dioxin) did not
      induce CYP1D1 transcript expression. Morpholino oligonucleotide knockdown of
      AHR2, which mediates induction of other CYP1s, did not affect CYP1D1 expression.
      Zebrafish CYP1D1 heterologously expressed in yeast exhibited ethoxyresorufin- and
      methoxyresorufin-O-dealkylase activities. Antibodies against a CYP1D1 peptide
      specifically detected a single electrophoretically-resolved protein band in
      zebrafish liver microsomes, distinct from CYP1A. CYP1D1 in zebrafish is a CYP1A
      like gene that could have metabolic functions targeting endogenous compounds.

PMID- 19103148
TI  - CYP3A4 ubiquitination by gp78 (the tumor autocrine motility factor receptor,
      AMFR) and CHIP E3 ligases.
AB  - Human liver CYP3A4 is an endoplasmic reticulum (ER)-anchored hemoprotein
      responsible for the metabolism of >50% of clinically prescribed drugs. After
      heterologous expression in Saccharomyces cerevisiae, it is degraded via the
      ubiquitin (Ub)-dependent 26S proteasomal pathway that utilizes Ubc7p/Cue1p, but
      none of the canonical Ub-ligases (E3s) Hrd1p/Hrd3p, Doa10p, and Rsp5p involved in
      ER-associated degradation (ERAD). To identify an Ub-ligase capable of
      ubiquitinating CYP3A4, we examined various in vitro reconstituted mammalian E3
      systems, using purified and functionally characterized recombinant components. Of
      these, the cytosolic domain of the ER-protein gp78, also known as the tumor
      autocrine motility factor receptor (AMFR), an UBC7-dependent polytopic RING
      finger E3, effectively ubiquitinated CYP3A4 in vitro, as did the UbcH5a-dependent
      cytosolic E3 CHIP. CYP3A4 immunoprecipitation coupled with anti-Ub immunoblotting
      analyses confirmed its ubiquitination in these reconstituted systems. Thus, both
      UBC7/gp78 and UbcH5a/CHIP may be involved in CYP3A4 ERAD, although their relative
      physiological contribution remains to be established.

PMID- 19103149
TI  - Human tissue factor pathway inhibitor-2 is internalized by cells and translocated
      to the nucleus by the importin system.
AB  - Tissue factor pathway inhibitor-2 (TFPI-2) is a serine proteinase inhibitor that
      induces caspase-mediated apoptosis when offered to a variety of tumor cells. In
      order to investigate the mechanism of TFPI-2-induced apoptosis, we initially
      studied the uptake and trafficking of TFPI-2 by HT-1080 cells. Exogenously
      offered TFPI-2 was rapidly internalized and distributed in both the cytosolic and
      nuclear fractions. Nuclear localization of TFPI-2 was also detected in a variety
      of endothelial cells constitutively expressing TFPI-2. Nuclear localization of
      TFPI-2 required a NLS sequence located in its Lys/Arg-rich C-terminal tail
      comprising residues 191-211, as a TFPI-2 construct lacking the C-terminal tail
      failed to localize to the nucleus. Complexes of TFPI-2 and importin-alpha were co
      immunoprecipitated from cell lysates of HT-1080 cells either offered or
      overexpressing this protein, providing evidence that TFPI-2 was shuttled to the
      nucleus by the importin system. Our results provide the initial description of
      TFPI-2 internalization and translocation to the nucleus in a number of cells.

PMID- 19103150
TI  - Lipid-induced conformation of helix 7 from the pore-forming domain of the
      Bacillus thuringiensis Cry4Ba toxin: implications for toxicity mechanism.
AB  - Helix 7 in the Cry4Ba-pore-forming domain contains conserved Tyr(249) and
      Phe(264) that are crucially involved in mosquito-larvicidal activity. We have now
      characterized lipid-induced conformation of a 27-residue Cry4Ba-alpha7 peptide in
      phospholipid membranes using ATR-FTIR and hydrogen/deuterium (H(+)/D(+)) exchange
      experiments. ATR-FTIR results showed that conformation of this peptide is
      influenced by lipid composition and peptide-lipid ratio. For zwitterionic
      membranes, 1,2-dimyristoyl-sn-glycero-3-phosphocholine (DMPC) or 1,2-didecanoyl
      sn-glycero-3-phosphocholine, the peptide adopted both alpha-helix and alpha
      structure, but only alpha-helical conformation was observed in anionic membranes
      (1,2-dimyristoyl-sn-glycero-3-phosphoglycerol). H(+)/D(+) exchange results showed
      protection of approximately 90% in DMPC for beta-form, while alpha-helical form
      was found preferentially on membrane surface with both critical aromatic residues
      pointing towards bilayers. Analysis of 10-ns simulations of Cry4Ba-alpha7 in DMPC
      supports the stability of alpha-helical and beta-conformations for membrane
      associated and membrane-inserted states, respectively. We suggest that this lipid
      induced conformational change of alpha7 is conceivably related to pore-forming
      mechanism as structural requirement for efficient membrane insertion.

PMID- 19103151
TI  - Purification, characterization and crystallization of menaquinol:fumarate
      oxidoreductase from the green filamentous photosynthetic bacterium Chloroflexus
      aurantiacus.
AB  - The integral membrane protein complex, menaquinol:fumarate oxidoreductase (mQFR)
      has been purified, identified and characterized from the thermophilic green
      filamentous anoxygenic photosynthetic bacterium Chloroflexus aurantiacus. The
      complex is composed of three subunits: a 74 kDa flavoprotein that contains a
      covalently bound flavin adenine dinucleotide, a 28 kDa iron-sulfur cluster
      containing polypeptide, and a 27 kDa transmembrane polypeptide, which is also the
      binding site of two b-type hemes and two menaquinones. The purified complex has
      an apparent molecular mass of 260 kDa by blue-native PAGE, which is indicative of
      a native homodimeric form. The isolated complex is active in vitro in both
      fumarate reduction and succinate oxidation. It has been analyzed by visible
      absorption, redox titration, chemical analysis and EPR spectroscopy. In addition,
      phylogenetic analysis shows that the QFR of both C. aurantiacus and Chlorobium
      tepidum are most closely related to those found in the delta-proteobacteria. The
      purified enzyme was crystallized and X-ray diffraction data obtained up to 3.2 A
      resolution.

PMID- 19103152
TI  - MtDNA mutations are a common cause of severe disease phenotypes in children with
      Leigh syndrome.
AB  - Leigh syndrome is a common clinical manifestation in children with mitochondrial
      disease and other types of inborn errors of metabolism. We characterised clinical
      symptoms, prognosis, respiratory chain function and performed extensive genetic
      analysis of 25 Swedish children suffering from Leigh syndrome with the aim to
      obtain insights into the molecular pathophysiology and to provide a rationale for
      genetic counselling. We reviewed the clinical history of all patients and used
      muscle biopsies in order to perform molecular, biochemical and genetic
      investigations, including sequencing the entire mitochondrial DNA (mtDNA), the
      mitochondrial DNA polymerase (POLGA) gene and the surfeit locus protein 1 (SURF1)
      gene. Respiratory chain enzyme activity measurements identified five patients
      with isolated complex I deficiency and five with combined enzyme deficiencies. No
      patient presented with isolated complex IV deficiency. Seven patients had a
      decreased ATP production rate. Extensive sequence analysis identified eight
      patients with pathogenic mtDNA mutations and one patient with mutations in POLGA.
      Mutations of mtDNA are a common cause of LS and mtDNA analysis should always be
      included in the diagnosis of LS patients, whereas SURF1 mutations are not a
      common cause of LS in Sweden. Unexpectedly, age of onset, clinical symptoms and
      prognosis did not reveal any clear differences in LS patients with mtDNA or
      nuclear DNA mutations.

PMID- 19103153
TI  - TMEM70 protein - a novel ancillary factor of mammalian ATP synthase.
AB  - An increasing number of patients with nuclear genetic defects of mitochondrial
      ATP synthase have been identified in recent years. They are characterized by
      early onset, lactic acidosis, 3-methylglutaconic aciduria, hypertrophic
      cardiomyopathy and encephalopathy and most cases have a fatal outcome. Patient
      tissues show isolated defect of the ATP synthase complex and its content
      decreases to > or =30% of normal due to altered enzyme biosynthesis and assembly.
      Gene mapping and complementation studies have identified mutations in TMEM70 gene
      encoding a 30kD mitochondrial protein of unknown function as the cause of the
      disease. An altered synthesis of this new ancillary factor in ATP synthase
      biogenesis was found in most of the known patients with decreased ATP synthase
      content. As revealed by phylogenetic analysis, TMEM70 is specific for higher
      eukaryotes.

PMID- 19103154
TI  - Induction of histidine decarboxylase in macrophages inhibited by the novel NF
      kappaB inhibitor (-)-DHMEQ.
AB  - Histamine often causes inflammation, and this amine is produced by histidine
      decarboxylase (HDC). We found that (-)-DHMEQ, an NF-kappaB inhibitor, inhibited
      lipopolysaccharide (LPS)-induced histamine production and HDC induction in mouse
      macrophage cell line RAW264.7. However, as there is no kappaB site in the HDC
      promoter, we studied the mechanism of inhibition. Knockdown of the transcription
      factor C/EBPbeta reduced the HDC expression in LPS-treated cells. (-)-DHMEQ
      inhibited the C/EBPbeta transcriptional activity in a reporter assay and in an
      electrophoresis mobility shift assay. But it did not inhibit the in vitro binding
      of C/EBPbeta to DNA. It also did not lower the nuclear amount of C/EBPbeta. On
      the other hand, the addition of recombinant p65, a component of NF-kappaB,
      enhanced the activity of C/EBPbeta acting as a cofactor in vitro. Then, we found
      that (-)-DHMEQ lowered the nuclear amount of p65. Thus, inhibition of the
      C/EBPbeta activity by (-)-DHMEQ would be due to a reduction in the amount of
      nuclear p65, which has a co-activator activity for C/EBPbeta that is essential
      for the HDC induction. (-)-DHMEQ may be useful as an anti-inflammatory agent by
      lowering the histamine production in the body.

PMID- 19103155
TI  - Molecular characterization of the protease from Clostridium botulinum serotype C
      responsible for nicking in botulinum neurotoxin complex.
AB  - A protease was purified from the culture medium of Clostridium botulinum serotype
      C strain Stockholm (C-St). The purified protease belonged to the cysteine
      protease family based on assays for enzyme inhibitors, activators and kinetic
      parameters. The protease formed a binary complex consisting of 41- and 17-kDa
      proteins held together non-covalently. The DNA sequence encoding the protease
      gene was shown to be a single open reading frame of 1593 nucleotides, predicting
      530 amino acid residues including a signal peptide. The N-terminal region of the
      native enzyme underwent further proteolytic modification after processing by a
      signal peptidase. The protease introduced intermolecular cleavage into an intact
      single chain botulinum neurotoxin (BoNT) at a specific site. Homology modeling
      and docking simulation of C-St BoNT and C-St protease demonstrated that the
      specific nicking-site of the BoNT appears to fit into the deep pocket in the
      active site of the protease.

PMID- 19103156
TI  - Lymphotoxin-alpha3 mediates monocyte-endothelial interaction by TNFR I/NF-kappaB
      signaling.
AB  - We recently reported that the single nucleotide polymorphisms of the lymphotoxin
      (LT)alpha gene, a member of the tumor necrosis factor (TNF) family, are closely
      related to acute myocardial infarction; however, the precise mechanism of LTalpha
      signaling in atherogenesis remains unclear. We investigated the role of LTalpha3,
      a secreted homotrimer of LTalpha, in monocyte-endothelial cell adhesion using
      cultured human umbilical vein endothelial cells (HUVEC). We found that LTalpha3
      induced cell adhesion molecules and activated NF-kappaB p50 and p65. LTalpha3
      also induced phosphorylation of Akt, phosphorylation and degradation of IkappaB,
      nuclear translocation of p65, and increased adhesion of THP1 monocytes to HUVEC.
      These effects were mediated by TNF receptor (TNFR) I and attenuated by the
      phosphatidylinositol triphosphate-kinase (PI3K) inhibitors LY294002 and
      Wortmannin. Thus, LTalpha3 mediates the monocyte-endothelial interaction via the
      classical NF-kappaB pathway following TNFR I/PI3K activation, indicating it may
      play a role in the development of coronary artery disease.

PMID- 19103157
TI  - A DNA-binding factor, ArfA, interacts with the bldH promoter and affects
      undecylprodigiosin production in Streptomyces lividans.
AB  - The fact that adpA promoter activity is enhanced by S-adenosylmethionine without
      the involvement of the A-factor/ArpA regulatory cascade suggests the existence of
      additional transcriptional regulators for adpA expression in Streptomyces
      griseus. In this study, an additional adpA promoter regulatory protein, named
      ArfA, that is conserved among many bacteria was identified using DNA affinity
      purification from the cell extracts of Streptomyces lividans. The interactions of
      ArfA with the adpA promoter from S. griseus and with the bldH promoter from S.
      lividans were specific and both adpA and bldH promoters required ArfA for the
      wild-type level of their expressions in S. lividans. bldH of S. lividans is a
      homolog of adpA of S. lividans. ArfA-deletion mutant had only 70% of the normal
      undecylprodigiosin production. This result was confirmed by reduced redD promoter
      activity in the ArfA-deletion mutant. These results suggest that ArfA is a new
      type of DNA-binding regulator.

PMID- 19103158
TI  - Allosteric regulation of human poly(A)-specific ribonuclease by cap and potassium
      ions.
AB  - Poly(A)-specific ribonuclease (PARN), a multi-domain dimeric enzyme, is a
      deadenylase in higher vertebrates and plants with the unique property of cap
      dependent catalysis and processivity. We found that PARN is an allosteric enzyme,
      and potassium ions and the cap analogue were effectors with binding sites located
      at the RRM domain. The binding of K(+) to the entire RRM domain led to an
      increase of substrate-binding affinity but a decrease in the cooperativity of the
      substrate-binding site, while the binding of the cap analogue decreased both the
      catalytic efficiency and the substrate-binding affinity. The dissimilar kinetic
      properties of the enzymes with and without the entire RRM domain suggested that
      the RRM domain played a central role in the allosteric communications of PARN
      regulation. The allostery is proposed to be important to the multi-level
      regulation of PARN to achieve precise control of the mRNA poly(A) tail length.

PMID- 19103159
TI  - PrP106-126 peptide disrupts lipid membranes: influence of C-terminal amidation.
AB  - PrP106-126 is located within the important domain concerning membrane related
      conformational conversion of human Prion protein (from cellular isoform PrP(C) to
      scrapie isoform PrP(Sc)). Recent advances reveal that the pathological and
      physicochemical properties of PrP106-126 peptide are very sensitive to its N
      terminal amidation, however, the detailed mechanism remains unclear. In this
      work, we studied the interactions of the PrP106-126 isoforms (PrP106-126(CONH2)
      and PrP106-126(COOH)) with the neutral lipid bilayers by atomic force microscopy,
      surface plasmon resonance and fluorescence spectroscopy. The membrane structures
      were disturbed by the two isoforms in a similarly stepwise process. The distinct
      morphological changes of the membrane were characterized by formation of semi
      penetrated defects and sigmoidal growth of flat high-rise domains on the
      supported lipid bilayers. However, PrP106-126(COOH) displayed a higher peptide
      lipid binding affinity than PrP106-126(CONH2) (approximately 2.9 times) and
      facilitated the peptide-lipid interactions by shortening the lag time. These
      results indicate that the C-terminal amidation may influence the pathological
      actions of PrP106-126 by lowering the interaction potentials with lipid
      membranes.

PMID- 19103160
TI  - Phosphorylation of RhoGDI1 by p21-activated kinase 2 mediates basic fibroblast
      growth factor-stimulated neurite outgrowth in PC12 cells.
AB  - We previously showed that p21-activated kinase 2 (PAK2), a major PAK isoform
      expressed in PC12 cells, mediates neurite outgrowth via Rac1 GTPase. RhoGDI1
      forms a complex with Rac1, resulting in its inhibition. Rac1 activation requires
      dissociation from RhoGDI1. Here, we show that PAK2 mediates basic fibroblast
      growth factor (bFGF)-stimulated neurite outgrowth via phosphorylation of RhoGDI1.
      RhoGDI1 was shown to be associated with PAK2, with phosphorylation of Ser34 and
      Ser101 by active PAK2 evident in vitro and in vivo. A RhoGDI1 phosphomimetic
      mutant (S34E/S101E) was dissociated from Rac1/Cdc42, whereas the wild-type or a
      nonphosphorylatable mutant (S34A/S101A) formed a tight complex. Consistent with
      this, PC12 cells expressing the phosphomimetic mutant displayed Rac1/Cdc42
      activation in response to bFGF stimulation. Neurite outgrowth was also enhanced
      in PC12 cells expressing the phosphomimetic mutant. These results suggest that
      PAK2-mediated RhoGDI1 phosphorylation stimulates dissociation of RhoGDI1
      Rac1/Cdc42 complex accompanied by relief of inhibitory effect on Rac1/Cdc42,
      which promotes neuronal differentiation.

PMID- 19103161
TI  - SNAP-25(1-180) enhances insulin secretion by blocking Kv2.1 channels in rat
      pancreatic islet beta-cells.
AB  - Voltage-gated outward K(+) currents from pancreatic islet beta-cells are known to
      repolarize the action potential during a glucose stimulus, and consequently to
      modulate Ca(2+) entry and insulin secretion. The voltage gated K(+) (Kv) channel,
      Kv2.1, which is expressed in rat islet beta-cells, mediates over 60% of the Kv
      outward K(+) currents. A novel peptidyl inhibitor of Kv2.1/Kv2.2 channels,
      guangxitoxin (GxTX)-1, has been shown to enhance glucose-stimulated insulin
      secretion. Here, we show that SNAP-25(1-180) (S180), an N-terminal SNAP-25
      domain, but not SNAP-25(1-206) (S206), inhibits Kv current and enhances glucose
      dependent insulin secretion from rat pancreatic islet beta-cells, and
      furthermore, this enhancement was induced by the blockade of the Kv2.1 current.
      This study indicates that the Kv2.1 channel is a potential target for novel
      therapeutic agent design for the treatment of type 2 diabetes. This target may
      possess advantages over currently-used therapies, which modulate insulin
      secretion in a glucose-independent manner.

PMID- 19103162
TI  - Efficient osteoblast differentiation from mouse bone marrow stromal cells with
      polylysin-modified adenovirus vectors.
AB  - Bone marrow stromal cells (BMSCs) are expected to be a source for tissue
      regeneration because they can differentiate into multiple cell types.
      Establishment of efficient gene transfer systems for BMSCs is essential for their
      application to regenerative medicine. In this study, we compared the transduction
      efficiency in mouse primary BMSCs by using fiber-modified adenovirus (Ad)
      vectors, and demonstrated that AdK7, which harbors a polylysin (K7) peptide in
      the C-terminus of the fiber knob, could efficiently express a transgene in BMSCs.
      Notably, AdK7 robustly drove transgene expression in more than 90% of the BMSCs
      at 3,000 vector particles/cell. Furthermore, we showed that in vitro and in vivo
      osteogenic potential of BMSCs was dramatically promoted by the transduction of
      Runx2 gene using AdK7. These results indicate that this transduction system could
      be a powerful tool for therapeutic applications based on BMSCs.

PMID- 19103163
TI  - Sequence specificity of the PHSRN peptide from fibronectin on corneal epithelial
      migration.
AB  - The Pro-His-Ser-Arg-Asn (PHSRN) sequence in fibronectin is a second cell-binding
      site that synergistically affects with Arg-Gly-Asp. The PHSRN peptide also
      induces cell invasion and accelerates wound healing. Here, we examined the
      sequence specificity of PHSRN on corneal epithelial migration using various
      synthetic peptides. Elongation and deletion analyses of Ac-PHSRN-NH(2) suggest
      that the five amino acid length was a minimum and essential sequence for
      promotion of rabbit corneal epithelial migration ex vivo. Additionally, alanine
      substituted analysis indicated that the Ser- and Arg-residues are critical for
      the biological activities. The Ser-Arg motif is involved in various biologically
      active peptides, suggesting that the unique sequence interacts with cellular
      receptor(s) and regulates biological functions. Further, the N-acetyl and C-amide
      of Ac-PHSRN-NH(2) contributed effectively for the chemical stability in tears.
      The Ac-PHSRN-NH(2) peptide has potential to use as a therapeutic reagent
      especially for corneal wound healing.

PMID- 19103164
TI  - Different reaction mechanisms for cis- and trans-prenyltransferases.
AB  - Octaprenyl diphosphate synthase (OPPs) and undecaprenyl diphosphate synthases
      (UPPs) catalyze consecutive condensation reactions of farnesyl diphosphate (FPP)
      with 5 and 8 isopentenyl diphosphate (IPP) to generate C(40) and C(55) products
      with trans- and cis-double bonds, respectively. In this study, we used IPP
      analogue, 3-bromo-3-butenyl diphosphate (Br-IPP), in conjunction with
      radiolabeled FPP, to probe the reaction mechanisms of the two prenyltransferases.
      Using this alternative substrate with electron-withdrawing bromo group at the C3
      position to slow down the condensation step, trapping of farnesol in the OPPs
      reaction from radiolabeled FPP under basic condition was observed, consistent
      with a sequential mechanism. In contrast, UPPs reaction yielded no farnesyl
      carbocation intermediate under the same condition with radiolabeled FPP and Br
      IPP, indicating a concerted mechanism. Our data demonstrate the different
      reaction mechanisms for cis- and tran-prenyltransferases although they share the
      same substrates.

PMID- 19103165
TI  - Released exopolysaccharide (r-EPS) produced from probiotic bacteria reduce
      biofilm formation of enterohemorrhagic Escherichia coli O157:H7.
AB  - Here, we characterized released-exopolysaccharides (r-EPS) from Lactobacillus
      acidophilus A4 with the goal of identifying natural compounds that represses
      biofilm formation. In plastic 96-well microplates that contained 1.0 mg/ml of r
      EPS, enterohemorrhagic Escherichia coli (EHEC) biofilms were dramatically
      decreased by 87% and 94% on polystyrene and polyvinyl chloride (PVC) surfaces,
      respectively. In the presence of r-EPS, neither their growth rate nor their
      autoinducer-2-like activity was affected on the EHEC O157:H7. Importantly,
      consistent reduction in biofilm formation was also observed when r-EPS was
      applied to the continuous-flow chamber models. In addition, we found that adding
      r-EPS significantly repressed biofilm formation by affecting genes related to
      curli production (crl, csgA, and csgB) and chemotaxis (cheY) in transcriptome
      analysis. Furthermore, these r-EPS could prevent biofilm formation by a wide
      range of Gram-negative and -positive pathogens. This property may lead to the
      development of novel food-grade adjuncts for microbial biofilm control.

PMID- 19103166
TI  - WGA-QD probe-based AFM detects WGA-binding sites on cell surface and WGA-induced
      rigidity alternation.
AB  - A strategy involving the conjugation of fluorescent quantum dot (QD) with wheat
      germ agglutinin (WGA) acting as fluorescent and topographic probes prior to cell
      surface staining is developed for fluorescence microscopy and atomic force
      microscopy (AFM). This strategy provided at least two advantages: (a) an
      amplified fluorescence of WGA-QD aggregates, strongly resistant to
      photobleaching, ensures repeated/real-time observations of the probe-labeled
      cells by fluorescence microscopy; (b) the enlarged size of WGA-QD probe makes it
      possible for labeled WGA to be distinguished from other membrane proteins by AFM.
      Here, the random distribution of WGA-binding sites on non-crosslinked cells and
      the uneven or polarized reorganization due to WGA-induced crosslinking on cell
      surfaces were studied using AFM-detectable WGA-QD probe. Moreover, we developed a
      method to rapidly detect the WGA-induced rigidity alternation of the whole cells,
      which is efficient and has the potentiality of being developed to a useful tool
      in clinical diagnosis.

PMID- 19103167
TI  - 3D cultured immortalized human hepatocytes useful to develop drugs for blood
      borne HCV.
AB  - Due to the high polymorphism of natural hepatitis C virus (HCV) variants,
      existing recombinant HCV replication models have failed to be effective in
      developing effective anti-HCV agents. In the current study, we describe an in
      vitro system that supports the infection and replication of natural HCV from
      patient blood using an immortalized primary human hepatocyte cell line cultured
      in a three-dimensional (3D) culture system. Comparison of the gene expression
      profile of cells cultured in the 3D system to those cultured in the existing 2D
      system demonstrated an up-regulation of several genes activated by peroxisome
      proliferator-activated receptor alpha (PPARalpha) signaling. Furthermore, using
      PPARalpha agonists and antagonists, we also analyzed the effect of PPARalpha
      signaling on the modulation of HCV replication using this system. The 3D in vitro
      system described in this study provides significant insight into the search for
      novel anti-HCV strategies that are specific to various strains of HCV.

PMID- 19103168
TI  - Differential regulation of proteins and phosphoproteins in rice under drought
      stress.
AB  - Drought is the largest constraint on rice production in Asia. Protein
      phosphorylation has been recognized as an important mechanism for environmental
      stress signaling. However, the differential expression of proteins and
      phosphoproteins induced by drought in rice is still largely unknown. In this
      paper, we report the identification of differentially expressed proteins and
      phosphoproteins induced by drought in rice using proteomic approaches. Three
      drought-responsive proteins were identified. Late embryogenesis abundant (LEA)
      like protein and chloroplast Cu-Zn superoxide dismutase (SOD) were up-regulated
      by drought whereas Rieske Fe-S precursor protein was down-regulated. Ten drought
      responsive phosphoproteins were identified: NAD-malate dehydrogenase,
      OSJNBa0084K20.14 protein, abscisic acid- and stress-inducible protein, ribosomal
      protein, drought-induced S-like ribonuclease, ethylene-inducible protein, guanine
      nucleotide-binding protein beta subunit-like protein, r40c1 protein,
      OSJNBb0039L24.13 protein and germin-like protein 1. Seven of these
      phosphoproteins have not previously been reported to be involved in rice drought
      stress. These results provide new insight into the regulatory mechanism of
      drought-induced proteins and implicate several previously unrecognized proteins
      in response to drought stress.

PMID- 19103169
TI  - Bone morphogenetic protein-2 induces chromatin remodeling and modification at the
      proximal promoter of Sox9 gene.
AB  - Sox9 is a key transcription factor which plays an important role in
      chondrogenesis. Although Bone Morphogenetic Protein-2 (BMP-2) has been reported
      to induce Sox9 expression, the underlying molecular mechanism remains elusive.
      Here, we used in vivo approaches to characterize BMP-2-induced alterations in
      chromatin organization around the Sox9 core promoter. Nuclease hypersensitive
      site mapping following BMP-2 stimulation showed an inducible hypersensitive site
      in the Sox9 proximal promoter. Immunoprecipitation (IP) experiments demonstrated
      that BMP-2 increased the association of the transcription factor NF-Y with
      histone acetyltransferase p300/CBP. Chromatin immunoprecipitation (ChIP) analysis
      showed the binding of the NF-Y-p300 complex to the Sox9 gene proximal promoter
      along with PCAF and RNA polymerase II. We also found that BMP-2 stimulation
      caused histone hyperacetylation and methylation at the Sox9 gene. Collectively,
      these data suggest that the activation of Sox9 gene transcription by BMP-2 is
      associated with chromatin remodeling and histone modification.

PMID- 19103170
TI  - Induction of autophagy by anthrax lethal toxin.
AB  - Autophagy is an evolutionary conserved intracellular process whereby cells break
      down long-lived proteins and organelles. Accumulating evidences suggest
      increasing physiological significance of autophagy in pathogenesis of infectious
      diseases. Anthrax lethal toxin (LT) exerts its influence on numerous cells and
      herein, we report a novel effect of LT-induced autophagy on mammalian cells.
      Several autophagy biochemical markers including LC3-II conversion, increased
      punctuate distribution of GFP-LC3 and development of acidic vesicular organelles
      (AVO) were detected in cells treated with LT. Analysis of individual LT component
      revealed a moderate increase in LC3-II conversion for protective antigen-treated
      cells, whereas the LC3-II level in lethal factor-treated cells remained
      unchanged. In addition, our preliminary findings suggest a protective role of
      autophagy in LT intoxication as autophagy inhibition resulted in accelerated cell
      death. This study presents a hitherto undescribed effect of LT-induced autophagy
      on cells and provides the groundwork for future studies on the implication of
      autophagy in anthrax pathogenesis.

PMID- 19103171
TI  - Generation of humanized anti-DNA hydrolyzing catalytic antibodies by
      complementarity determining region grafting.
AB  - Humanization of nonhuman antibodies (Abs) has been carried out mainly for Abs
      which bind to antigen without catalytic activity. Here we report humanization of
      mouse-originated 3D8 (m3D8) mAbs (scFv, VH, and VL) with DNA hydrolyzing
      catalytic activity by grafting the complementarity determining regions (CDRs)
      into the corresponding regions of a fixed human framework scaffold, generating
      humanized 3D8 (h3D8) Abs in the respective format of scFv, VH, and VL. h3D8 Abs
      retained comparable DNA binding and hydrolyzing activities to those of the
      corresponding m3D8 Abs. Our results suggest that CDRs of anti-DNA hydrolyzing Abs
      might possess the intrinsic properties of DNA binding and hydrolyzing activities.

PMID- 19103172
TI  - SLPI prevents cytokine release in mite protease-exposed conjunctival epithelial
      cells.
AB  - House dust mites are a major source of allergens associated with allergic
      diseases including allergic conjunctivitis. Here, we demonstrate that mite
      derived serine protease activity induces the release of cytokines from human
      ocular conjunctival epithelial cells in vitro and innate antiproteases, secretory
      leukocyte protease inhibitor (SLPI) and alpha1-antitrypsin, can inhibit the
      response. An extract prepared from a whole-mite culture induced the release of IL
      6 and IL-8 and upregulated their gene expression in the human conjunctival
      epithelial cell line Chang, responses which were inhibited not only by a
      synthetic serine protease-specific inhibitor, AEBSF, but also by SLPI and alpha1
      antitrypsin at a physiologically relevant concentration. The findings suggest a
      homeostatic role for SLPI and alpha1-antitrypsin against the proteases contained
      in allergen sources in the ocular conjunctiva and that exposure to house dust
      particles containing mite-derived serine protease activity could be involved in
      the initiation of sensitization through the ocular conjunctival epithelium and/or
      exacerbation of allergic conjunctivitis.

PMID- 19103173
TI  - Immunostimulation and anti-DNA antibody production by backbone modified CpG-DNA.
AB  - Oligodeoxynucleotides containing immunostimulatory CpG motifs (CpG-DNA) have
      gained attention as potentially useful therapeutics. However, the
      phosphorothioate-modified CpG-DNAs (PS-ODN) can induce backbone-related side
      effects. Here, we compared the immunostimulatory activity of natural
      phosphodiester CpG-DNA (PO-ODN) from Mycobacterium bovis and PS-ODN in mice. Both
      PO-ODN and PS-ODN induced production of IL-12. PS-ODN increased spleen weights,
      spleen cell numbers, and the migration of macrophages into the peritoneal cavity
      in the mice in a CG sequence-dependent manner. PS-ODN induced anti-PS-ODN
      antibody production in the mice, and the PS-ODN-specific IgM was cross-reactive
      with other PS-ODNs in a CG sequence-independent manner. In contrast, PO-ODN did
      not affect on spleen weights, cell numbers, or IgM production. These results may
      provide an explanation for the side effects in immunotherapeutic application of
      PS-ODN. They also suggest that PO-ODN may be more optimal than PS-ODN to enhance
      innate immune responses without severe side effects.

PMID- 19103174
TI  - Characterization of mutant mice that express polyglutamine in cerebellar Purkinje
      cells.
AB  - We recently produced transgenic mice that expressed an abnormally expanded
      polyglutamine (polyQ) specifically in cerebellar Purkinje cells (polyQ mice). The
      polyQ mice showed inclusion body formation, cerebellar atrophy and severe ataxia.
      Here we analyzed polyQ mice using immunohistochemistry, immunoelectronmicroscopy
      and electrophysiology. A diffuse form of polyQ was detected in the nucleus.
      Interestingly, ubiquitinated large inclusions were located close to, but
      apparently outside of the soma of Purkinje cells. Infusion of lucifer yellow into
      Purkinje cells clearly indicated the traffic between the periplasmic inclusions
      and soma of Purkinje cells. To examine whether the formation of periplasmic
      inclusions was an active process or a result of cell death, the polyQ mouse
      cerebellum was immunolabeled for cleaved caspase-3, a marker of apoptosis.
      Interestingly, no Purkinje cells in P80 polyQ mice immunoreacted with the
      antibody. The results were substantiated by electrophysiological assay, which
      showed that P80 Purkinje cells with large periplasmic inclusions were
      functionally active: excitatory postsynaptic currents (EPSCs) were reliably
      evoked upon electrical stimulation of parallel fibers (PFs) or climbing fibers
      (CFs), and current injection into Purkinje cells generated action potentials;
      however, the frequency of action potentials in response to various volumes of
      current injection was consistently lower in polyQ mice than in wild-type animals,
      and aberrant innervation by multiple CFs was detected in polyQ mouse Purkinje
      cells. These results suggest that Purkinje cells with periplasmic inclusions were
      not apoptotic, but their functions were substantially impaired, which could
      contribute to the severe ataxic phenotype.

PMID- 19103175
TI  - Adiponectin acts in the nucleus of the solitary tract to decrease blood pressure
      by modulating the excitability of neuropeptide Y neurons.
AB  - Adiponectin is an adipocyte derived hormone which acts in the CNS to control
      autonomic function, energy and cardiovascular homeostasis. Two 7-transmembrane
      domain receptors, AdipoR1 and AdipoR2, expressed in the hypothalamus and
      brainstem mediate the actions of adiponectin. The medulla's nucleus of the
      solitary tract (NTS) is the primary viscerosensory integration site and an
      important nucleus in the regulation of cardiovascular function. Here we show the
      localization of both AdipoR1 and AdipoR2 mRNA in the NTS. We have investigated
      the consequences of receptor activation in response to exogenous application of
      adiponectin on cardiovascular (blood pressure and heart rate monitoring in vivo),
      and single neuron (whole cell current-clamp recordings in vitro) function.
      Microinjection of adiponectin in the medial NTS (mNTS) at the level of the area
      postrema resulted in a decrease in BP (mean AUC= -2055+/-648.1, n=5, mean maximum
      effect: -11.7+/-3.6 mm Hg) while similar commissural NTS (cNTS) microinjections
      were without effect. Patch clamp recordings from NTS neurons in a medullary slice
      preparation showed rapid (within 200 s of application) reversible (usually within
      1000 s following washout) effects of adiponectin on the membrane potential of 62%
      of mNTS neurons tested (38/61). In 34% (n=21) of mNTS neurons adiponectin induced
      a depolarization of membrane potential (6.8+/-0.9 mV), while the remainder of
      mNTS cells influenced by adiponectin (n=17) hyperpolarized in response to this
      adipokine (-5.4+/-0.7 mV). Post-hoc single cell RT-PCR (ssRT-PCR) analysis of
      neurons showed that the majority of NPY mRNA positive mNTS neurons were
      depolarized by adiponectin (7/11), while 4 of these depolarized cells were also
      GAD67 positive. The results presented in this study suggest adiponectin acts in
      the NTS to control BP and suggest that such effects may occur as a direct result
      of the ability of this adipokine to modulate the excitability of discrete groups
      of neurons in the NTS. These studies identify the mNTS as a new CNS site which
      adiponectin may act to influence central autonomic processing.

PMID- 19103176
TI  - Intraspinal cord graft of autologous activated Schwann cells efficiently promotes
      axonal regeneration and functional recovery after rat's spinal cord injury.
AB  - Basic research in spinal cord injury (SCI) has made great strides in recent
      years, and some new insights and strategies have been applied in promoting
      effective axonal regrowth and sprouting. However, a relatively safe and efficient
      transplantation technique remains undetermined. This study, therefore, was aimed
      to address a question of how to graft Schwann cells to achieve the best possible
      therapeutic effects. To clarify the issue, the rats were subjected to spinal cord
      injury at T10. Autologous activated Schwann cells (AASCs) were obtained by prior
      ligation of saphenous nerve and subsequently isolated and purified in vitro and
      then grafted into spinal cord-injured rats via three different routes (group I:
      intravenous, group II: intrathecal and group III: intraspinal cord). Neurologic
      function was serially evaluated by Basso, Beattie, Bresnahan locomotor rating
      scale and footprint analysis. We also evaluated the migration of the transplanted
      cells at 2 weeks after transplantation. Using biotinylated dextran amine (BDA)
      anterograde tracing, we demonstrated that more regenerative axons of
      corticospinal tract (CST) surrounding the injured cavity in group III than those
      in the other two groups, and we also confirmed it further by quantitative
      analysis. The microenvironment surrounding the injured spinal cord has been
      improved to the greatest extent in group III, as determined by immunohistological
      staining. Relatively complete myelin sheaths and more neurofilaments in axons
      were found in groups II and III than those in group I under electron microscopy.
      The results showed that intraspinal cord injection of AASCs promoted recovery of
      hindlimb locomotor function of injured rats more efficiently than the other
      grafting routes. In addition, intact myelin sheaths and sufficient neurofilaments
      in axons were not adequate for full functional recovery after SCI, suggesting
      that reestablishment of normal synaptic connection is indispensable. The findings
      in this study strongly suggest that transplantation of AASCs directly into the
      spinal cord may be one of the promising candidates for potential scaffold for
      injured spinal cord, and such strategy of transplantation of AASCs could be
      hopeful to treat patients with SCI.

PMID- 19103177
TI  - The ERK5-MEF2C transcription factor pathway contributes to anti-apoptotic effect
      of cerebral ischemia preconditioning in the hippocampal CA1 region of rats.
AB  - The purpose of the present study was to investigate the role of myocyte enhancer
      binding factor 2C (MEF2C), a common substrate of p38 kinase and extracellular
      signal-regulated kinase 5 (ERK5) in the hippocampal CA1 region following cerebral
      ischemia preconditioning (CIP) and without CIP. In animals that did not undergo
      preconditioning, MEF2C was significantly activated with an early peak at 30 min
      of reperfusion, which was followed by a pronounced decrease of MEF2C protein
      levels in the late phase of reperfusion (3-5 d). Co-immunoprecipitation studies
      failed to show an interaction between ERK5 and MEF2C, and ERK5-antisense
      oligonucleotide (ERK5-AS) had no effect on MEF2C activation, suggesting that the
      MEF2C activation is mediated by a kinase other than ERK5. Following
      preconditioning (3 min ischemia), MEF2C was strongly activated during the late
      stage of reperfusion (6 h-5 d). Co-immunoprecipitation studies showed that the
      interaction of ERK5 and MEF2C significantly increased at 3 d of reperfusion, and
      this increase was markedly inhibited by ERK5-AS. Inhibition of the ERK5-MEF2C
      pathway resulted in a significant increase in the number of TUNEL-positive
      apoptotic cells compared with CIP groups in the hippocampal CA1 region, and
      abolished the neuroprotective effect induced by CIP. Taken together, these
      results demonstrate that ERK5-MEF2C signaling is significantly enhanced in the
      hippocampus CA1 following CIP, and that ERK5-MEF2C signaling plays a critical
      role in the mediation of the anti-apoptotic and neuroprotective actions of
      ischemic preconditioning.

PMID- 19103178
TI  - ERP correlates of intentional forgetting.
AB  - In this study we investigated the neurocognitive processes underlying the control
      of memory retrieval. In a Think/No-Think paradigm, adopted for the use in an
      event-related potential (ERP) experiment, participants learned word pairs and
      were subsequently presented with cue words and asked to either suppress or to
      recall the target word. During final cued recall tests for all initially learned
      targets, memory for the to-be-suppressed or to be-recalled items were tested.
      Memory for to be-recalled items was enhanced but no forgetting of to-be
      suppressed items was obtained. The ERPs in the test phase were separated on the
      basis of prior learning success and failure, allowing separate analyses of
      strategic memory control, i.e. attempts to retrieve or to avoid retrieval and the
      outcome of these processes, i.e. successful retrieval and retrieval avoidance. An
      early P2 component and a parietal positivity were related to retrieval attempts
      and a centro-parietal N2 component was associated with attempts to avoid memory
      retrieval. The parietal positivity was attenuated for No-Think trials on learned
      items, for which item-specific memories exist. However, under the present testing
      conditions and in contrast to prior studies (Bergstrom, Velmans, de Fockert,
      Richardson-Klavehn, 2007) the parietal positivity was also sensitive to mere
      retrieval attempts. To examine whether similar neural systems are involved in the
      inhibitory control of unwanted memories and prepotent motor responses, a motor
      stopping experiment using a stop signal task was conducted with the same
      participants. Successful stopping was associated with an enhanced stop signal N2
      that showed a similar centro-parietal scalp distribution as the aforementioned N2
      to No-Think trials. As both components were significantly correlated, we assumed
      that some of the systems recruited to override prepotent motor responses are also
      involved to suppress memory retrieval.

PMID- 19103180
TI  - Inflammatory mediators and blood brain barrier disruption in fatal brain edema of
      diabetic ketoacidosis.
AB  - Brain edema (BE) is an uncommon but life-threatening complication of severe
      diabetic ketoacidosis (DKA) and its treatment. Despite advances in treatment of
      DKA, the pathogenesis of both initiation and progression of the associated BE is
      unclear. In the present study we examined the blood brain barrier (BBB) integrity
      and the potential involvement of the inflammatory mediators in BBB breakdown in
      two cases of fatal BE associated with DKA. In both cases there were typical signs
      of disruption of the BBB manifested by the absence of tight junction proteins
      (occludin, claudin-5, ZO-1 and JAM-1) in the parenchymal blood vessels, as well
      as albumin extravasation in examined brain areas. The neuroinflammatory markers
      chemokine CCL2, NF-kappaB and nitrotyrosine were localized in the perivascular
      areas of the disrupted BBB and diffusely distributed in the brain parenchyma. Our
      data indicate that neuroinflammation plays a role in the BBB disruption of the
      fatal BE of DKA.

PMID- 19103179
TI  - Immunocytochemical analysis of retinal neurons under electrical stimulation.
AB  - To function successfully, a retinal prosthesis needs to provide effective
      stimulation in a safe manner. To date, most studies have been dedicated to
      assessing proper stimulation parameters, for example, determining stimulus
      threshold. Few studies have looked at the effects of prolonged stimulation on
      retinal morphology. One previous study did show gross morphological changes in
      the rat retina due to mechanical pressure, with and without electrical
      stimulation (Colodetti, L., Weiland, J.D., Colodetti, S., Ray, A., Seiler, M.J.,
      Hinton, D.R., Humayun, M.S., 2007). Here, we used immunocytochemistry to
      investigate the effects of the same experimental conditions on neuronal structure
      in finer detail. For this purpose, we first defined four experimental groups. In
      Group 1, the stimulating electrode was near but did not contact the retina, and
      we did not apply current pulses. In Group 2, the electrode also did not contact
      the retina, but we applied current pulses of 0.09 microC/phase. In Group 3, the
      stimulating electrode directly contacted the retina, but we did not apply current
      pulses. In Group 4, the stimulating electrode directly contacted the retina, and
      we applied current pulses of 0.09 microC/phase. We found neural damage only in
      the outer retina, including a disturbance of synaptic vesicle proteins in the
      photoreceptor terminals and a remodeling of horizontal and rod bipolar cells'
      processes. These results show that, although gross morphological changes are
      mainly concentrated around the area of electrode contact, immunocytochemistry can
      reveal changes in adjacent areas as well.

PMID- 19103181
TI  - Effects of memantine and galantamine given separately or in association, on
      memory and hippocampal neuronal loss after transient global cerebral ischemia in
      gerbils.
AB  - Galantamine is an acetylcholinesterase inhibitor and memantine is a non
      competitive antagonist of NMDA receptors that are being used to treat Alzheimer's
      disease (AD) patients. The fact that drugs with different mechanisms of action
      are available to treat AD introduces the prospect of prescribing drug
      combinations to amplify drug efficacy. This study was planed to evaluate the
      potential neuroprotective effects of galantamine combined with memantine in a
      transient global cerebral ischemia model in gerbils. Animal groups included in
      the study were: sham, ischemia, and ischemia plus galantamine (1 mg/kg and 10
      mg/kg), memantine (10 mg/kg and 20 mg/kg), 1 mg/kg galantamine plus 10 mg/kg
      memantine, and 10 mg/kg galantamine plus 10 mg/kg memantine, respectively.
      Surviving pyramidal neurons in the CA1 subfield of the hippocampus, TUNEL,
      caspase-3 and SOD-2 immunohistochemistries, and the object placement test were
      evaluated 72 h after reperfusion. Memantine did not exert a clear neuroprotective
      effect, nor did it prevent spatial memory loss. In a previous study using the
      same experimental model, galantamine was neuroprotective and improved spatial
      memory. In this study, the association of 10 mg/kg memantine with 10 mg/kg
      galantamine increased the number of living pyramidal neurons, reduced TUNEL,
      active caspase-3 and SOD-2 immunoreactivity, and preserved spatial memory after
      ischemia-reperfusion injury; however, the effects of the combination were not
      statistically different from those observed in animals treated with galantamine
      alone. We believe these results are of interest from a clinical point of view
      because the association of both drugs is being used in clinical practice and in
      clinical trials to treat Alzheimer's disease and vascular dementia.

PMID- 19103182
TI  - Mesenchymal and neural stem cells labeled with HEDP-coated SPIO nanoparticles: in
      vitro characterization and migration potential in rat brain.
AB  - Mesenchymal stem cells (MSC) may transdifferentiate into neural cells in vitro
      under the influence of matrix molecules and growth factors present in neurogenic
      niches. However, further experiments on the behavior of such stem cells remain to
      be done in vivo. In this study, rat MSC (rMSC) have been grafted in a neurogenic
      environment of the rat brain, the subventricular zone (SVZ), in order to detect
      and follow their migration using superparamagnetic iron oxide (SPIO)
      nanoparticles. We sought to characterize the potential effect of iron loading on
      the behavior of rMSC as well as to address the potential of rMSC to migrate when
      exposed to the adequate brain microenvironment. 1-hydroxyethylidene-1.1
      bisphosphonic acid (HEDP)-coated SPIO nanoparticles efficiently labeled rMSC
      without significant adverse effects on cell viability and on the in vitro
      differentiation potential. In opposition to iron-labeled rat neural stem cells
      (rNSC), used as a positive control, iron-labeled rMSC did not respond to the SVZ
      microenvironment in vivo and did not migrate, unless a mechanical lesion of the
      olfactory bulb was performed. This confirmed the known potential of iron-labeled
      rMSC to migrate toward lesions and, as far as we know, this is the first study
      describing such a long distance migration from the SVZ toward the olfactory bulb
      through the rostral migratory stream (RMS).

PMID- 19103183
TI  - Mixed pro and antisaccade performance in children and adults.
AB  - Pro and antisaccades are usually presented in blocks of similar type but they can
      also be presented such that prosaccade and antisaccade eye movements are mixed
      and a cue, usually the shape/colour of the fixation target or the peripheral
      target, determines which type of eye movement is required in a particular trial.
      A mixed-saccade task theoretically equalizes the inhibitory requirements for pro
      and antisaccades. Using a mixed-saccade task paradigm the aims of the study were
      to: 1) compare pro and antisaccades of children, 2) compare performance of
      children and adults and 3) explore the effect of increased working memory load in
      adults. The eye movements of 22 children (5-12 years) and 22 adults (20-51 years)
      were examined using a video-based eye tracking system (El-Mar Series 2020 Eye
      Tracker, Toronto, Canada). The task was a mixed-saccade task of pro and
      antisaccades and the colour of the peripheral target was the cue for whether the
      required saccade was to be a pro or an antisaccade. The children performed the
      mixed-saccade task and 11 adults performed the same mixed-saccade task alone and
      in a dual-task paradigm (together with mental subtraction or number repetition).
      A second group of 11 adults performed the mixed-saccade task alone. Children made
      mainly antisaccade errors. The adults' error rates increased in the mental
      subtraction dual-task condition but both antisaccade and prosaccade errors were
      made. It was concluded that the increased error rates of these two groups are
      reflective of different processing dynamics.

PMID- 19103184
TI  - Neuroprotection by rasagiline in thiamine deficient rats.
AB  - Thiamine deficiency (TD) in rats is a model of chronic impairment of oxidative
      metabolism leading to neuronal loss. TD rats exhibit neuropathological,
      behavioral and cognitive abnormalities. The aim of this study was to use this
      syndrome to assess the neuroprotective potential of drugs in a whole animal
      model. TD was produced in rats using the following protocol: thiamine deficient
      diet, daily injections of the central thiamine antagonist, pyrithiamine (0.5
      mg/kg), and the test drugs, the selective monoamine oxidase (MAO) B inhibitors,
      rasagiline (1 or 3 mg/kg/day) and selegiline (2.4 or 8 mg/kg/day). Normal rats
      and untreated TD rats served as controls. Upon the appearance of neurological
      symptoms, the TD protocol was suspended, rats were transferred to a regular diet,
      pyrithiamine and test drug injections were terminated and rats were injected with
      3 daily doses of thiamine (100 mg/kg). Neuroprotective potential was assessed by:
      general behavioral observations, cognitive testing using the Morris water maze
      and histopathological examination of the brains. Rasagiline but not selegiline
      significantly delayed the onset and severity of the neurological symptoms of TD.
      In the Morris water maze, TD-untreated rats displayed severe cognitive impairment
      while rasagiline-treated rats were similar to control rats and significantly
      different from TD-untreated rats. The effects were dose related. Selegiline
      treatment had no significant protective effect. TD-untreated brains displayed
      extensive gliotic and necrotic lesions mainly in the thalamus and posterior
      collicular nucleus, which were significantly reduced in the rasagiline-treated TD
      rats. These findings demonstrate significant neuroprotection by rasagiline with
      possible implications for clinical neurodegenerative disorders.

PMID- 19103185
TI  - p300 expression is induced by oxygen deficiency and protects neuron cells from
      damage.
AB  - Low oxygen level or oxygen deficiency (hypoxia) is a major factor causing
      neuronal damage in many diseases. Inducing cell adaptation to hypoxia is an
      effective method for neuroprotection that can be achieved by either inhibiting
      the death effectors or enhancing the survival factors. Transcription coactivator
      p300 is necessary for hypoxia-induced transcriptional activation and plays an
      important role in neuron survival. However, the alteration of p300 expression
      under hypoxia condition and its role in hypoxia-induced neuronal damage remain
      unclear. In this study, the distribution of p300 in rat brain and the alteration
      of its expression in rat hippocampus during hypobaric hypoxia exposure were
      detected. In addition, the role of p300 in neuronal-like PC12 cell damage induced
      by oxygen deficiency (3% oxygen) was evaluated. Our results showed that p300
      protein was mainly expressed in the cells expressed beta-tubulin III in the
      cerebral cortex, hippocampus, cerebellum cortex, medulla oblongata and
      hypothalamus. Less or no positive signal of p300 expression was observed in beta
      tubulin III negative cells. This indicated that p300 was predominantly expressed
      in neurons of rat brain. Furthermore, p300 expression was up-regulated in rat
      hippocampus during hypoxia exposure and in neuronal-like PC12 cells under 3%
      oxygen condition. Interestingly, neuronal-like PC12 cell damage induced by oxygen
      deficiency (3% oxygen) was increased by suppression of p300 expression with short
      hairpin RNA (shRNA). These data indicate that p300 is an important molecule for
      neuroprotection under hypoxia.

PMID- 19103186
TI  - The inhibition of lipoperoxidation by mesoionic compound MI-D: a relationship
      with its uncoupling effect and scavenging activity.
AB  - Important biological activities have been described for mesoionic compounds. We
      previously reported that MI-D (4-phenyl-5-(4-nitro-cinnamoyl)-1,3,4-thiadiazolium
      2-phenylamine chloride) inhibited the respiratory chain, collapsed the
      transmembrane potential, and stimulated ATPase activity in intact rat liver
      mitochondria. It is known that drugs that affect mitochondrial membrane potential
      may facilitate the induction of cell death by apoptosis. Mitochondria have also a
      central role in the generation of reactive oxygen species, therefore it would be
      important to investigate how MI-D could affect processes related to oxidative
      stress. In this work, we evaluated the effects of MI-D on the lipoperoxidation
      and its ability to scavenge free radicals. Interestingly, it was observed that MI
      D promoted a strong inhibition of the lipoperoxidation induced by Fe(3+)-ADP/2
      oxoglutarate in isolated mitochondria (95%+/-0.27 at the highest concentration of
      80 nmol mg(-1) protein) in a dose-dependent manner. However, at the same
      concentration its effect was less intense (22%+/-3.46) when the lipoperoxidation
      was initiated by peroxyl radicals generated from the azocompound AAPH. Lipid
      peroxidation in both coupled and uncoupled submitochondrial particles initiated
      with Fe(2+)/NADH was also inhibited by MI-D. The inhibition was about four times
      greater in coupled particles (approximately 34% at 80 nmol mg(-1) protein) in
      relation to uncoupled. MI-D inhibited the soybean phosphatidylcholine liposomes
      lipoperoxidation in a dose-dependent manner (5-80 microM) regardless of the
      radical being generated in lipid or aqueous phase. The mesoionic compound showed
      ability of scavenging superoxide radical (7, 11 and 31% for 25, 38 and 80 microM,
      respectively). Our results strongly suggest that the inhibition of
      lipoperoxidation promoted by MI-D is due to its scavenger action and to its
      previously described uncoupling effect.

PMID- 19103187
TI  - Apolipoprotein E4 allele influences the response of plasma triglyceride levels to
      tamoxifen in breast cancer patients.
AB  - BACKGROUND: Apolipoprotein E4 (APOE4) allele is an important risk factor for
      breast cancer and affects clearance of chylomicron remnants. Tamoxifen therapy
      increases serum triglyceride levels and sometimes inducing severe
      hypertriglyceridemia in breast cancer patients. METHODS: Thirty-three women with
      breast cancer were recruited to examine the APOE polymorphism and fasting plasma
      lipid profiles before and after tamoxifen treatment for 6 months. RESULTS: We
      found that plasma lipid profiles changed in accordance with the APOE4 allele
      after tamoxifen treatment for 6 months. Especially plasma triglyceride levels
      significantly decreased in the APOE4-positive patients (p=0.025), while there was
      no change in APOE4-negative patients (p=0.189). The total plasma cholesterol
      levels were reduced in APOE-4 positive patients after 6-month tamoxifen treatment
      (p=0.014). The levels of plasma low density lipoprotein cholesterol and high
      density lipoprotein cholesterol significantly decreased in both APOE4-negative
      and APOE4-positive patients. CONCLUSIONS: These findings indicate that the
      effects of tamoxifen on plasma triglyceride levels are modified by APOE
      polymorphism. Breast cancer patients with APOE4 allele have low plasma
      triglyceride levels when receiving tamoxifen therapy. Therefore, we suggest that
      APOE gene polymorphism is a critical validation before tamoxifen treatment in
      breast cancer patients.

PMID- 19103188
TI  - Evaluation of whole antioxidant defenses of human mononuclear cells by a new in
      vitro biological test: lack of correlation between erythrocyte and mononuclear
      cell resistance to oxidative stress.
AB  - OBJECTIVES: This work aims to evaluate the resistance of mononuclear cells to
      oxidative stress using a "KRL" test, formerly utilized to evaluate the resistance
      of erythrocyte to free radicals. METHODS: The "KRL" test evaluates the resistance
      to lysis of cells treated by free radicals generated under standardized
      conditions. RESULTS: We defined new analytical parameters (level of radical
      production, time course, number of cells) to obtain an accurate assay determining
      the resistance to oxidative stress of mononuclear cells, in comparison to that of
      erythrocytes. This test allows the evaluation of change in the redox state of
      mononuclear cells (improved by an antioxidant mix or deteriorated by antimycin A
      induced mitochondrial radical overproduction). Interestingly, our data show that
      the sensitivity of mononuclear cells to oxidative stress is not correlated with
      the susceptibility of erythrocytes to oxidative stress. CONCLUSIONS: The
      quantification of the susceptibility of mononuclear cells to oxidative stress
      gives additional information (in addition to erythrocyte resistance) and could be
      helpful for patients with chronic inflammation.

PMID- 19103189
TI  - TGF-beta3 and TNFalpha perturb blood-testis barrier (BTB) dynamics by
      accelerating the clathrin-mediated endocytosis of integral membrane proteins: a
      new concept of BTB regulation during spermatogenesis.
AB  - In adult mammals such as rats, the blood-testis barrier (BTB) conferred by
      adjacent Sertoli cells in the seminiferous epithelium segregates post-meiotic
      germ cell development from the systemic circulation and is one of the tightest
      blood-tissue barriers. Yet it must "open" transiently at stages VIII to IX of the
      epithelial cycle to accommodate the migration of preleptotene/leptotene
      spermatocytes. While this is a vital event of spermatogenesis, the mechanism(s)
      that regulates BTB dynamics is virtually unknown. Recent studies have suggested
      that transforming growth factor-beta3 (TGF-beta3) and tumor necrosis factor alpha
      (TNFalpha) secreted by Sertoli and germ cells into the microenvironment of the
      BTB are capable of inducing reversible BTB disruption in vivo, apparently by
      reducing the steady-state levels of occludin and zonula occludens-1 (ZO-1) at the
      BTB via the p38 mitogen activated protein (MAP) kinase signaling pathway. In this
      study, local administration of TGF-beta3 (200 ng/testis) to the testis was shown
      to reversibly perturb the BTB integrity in vivo. We next sought to delineate the
      mechanism by which these cytokines maintain the steady-state level of integral
      membrane proteins: occludin, junctional adhesion molecule-A (JAM-A) and N
      cadherin at the BTB. Primary Sertoli cells cultured in vitro were shown to
      establish intact tight junctions and functional BTB within two days when assessed
      by transepithelial electrical resistance (TER) measurement across the cell
      epithelium. Sertoli cell integral membrane protein internalization at the BTB was
      assessed by biotinylation of cell surface proteins, to be followed by tracking
      the endocytosed/biotinylated proteins by using specific antibodies. Both TGF
      beta3 (3 ng/ml) and TNFalpha (10 ng/ml) were shown to significantly accelerate
      the kinetics of internalization of JAM-A, N-cadherin, and occludin versus
      controls. Treatment of cells with phenylarsine oxide (PAO) at 10 microM that
      blocks clathrin-mediated endocytosis was shown to inhibit the TGF-beta3-induced
      protein internalization. This inhibition of TGF-beta3-mediated protein
      endocytosis was further validated by silencing of clathrin. The specific effect
      of TGF-beta3 on protein internalization was further confirmed by RNAi using
      specific TGF-beta receptor I (TbetaR1) siRNA duplexes. When TbetaR1 was knocked
      down, the TGF-beta3-induced increase in the kinetics of JAM-A and occludin
      endocytosis was abolished, making them indistinguishable from controls,
      illustrating the specificity of the TGF-beta3 effects on protein endocytosis. In
      summary, this report demonstrates for the first time that BTB dynamics are
      regulated by TGF-beta3 and TNFalpha via an enhancement of protein endocytosis at
      the BTB.

PMID- 19103190
TI  - Genetic interplays between Msx2 and Foxn1 are required for Notch1 expression and
      hair shaft differentiation.
AB  - Hair shafts are produced from stem cells located in the bulge. Our knowledge of
      the genetic pathways regulating cell fate acquisition in the immediate
      descendents of these stem cells, and fate maintenance in their committed progeny,
      is still incomplete. One pathway involved in fate maintenance within the hair
      matrix is the Notch pathway. Here we use compound genetic mutants to demonstrate
      that two transcription factors, Msx2 and Foxn1, are both required to maintain
      Notch1 expression in the hair follicle matrix. In their absence, Notch1 is
      markedly reduced in hair matrix; as a consequence, medulla and inner root sheath
      (IRS) differentiation is impaired. Our studies also suggest that Foxn1 is a
      direct activator of the Notch1 promoter activity through one or more putative
      Foxn1 consensus binding sites located within the 4.7 kb of mouse Notch1 promoter.
      Since recombinant human BMP4 can induce Foxn1 expression in Msx2-deficient hair
      follicles, and that their effect on cortical keratin expression appears
      synergistic, we suggest that these two genes function in parallel pathways
      downstream of BMP signaling and upstream of Notch1. Independent from their role
      in Notch activation, Msx2 and Foxn1 also contribute to the expression of several
      cortical and cuticle keratins. The impact of these additional defects is the
      complete loss of all visible external hairs, not seen in Notch1 mutants. Our
      results position Msx2 and Foxn1 upstream of Notch1 within the hair matrix and
      demonstrate that together these factors play a pivotal role in IRS, cortex and
      medulla differentiation.

PMID- 19103191
TI  - Differential regulation of ParaHox genes by retinoic acid in the invertebrate
      chordate amphioxus (Branchiostoma floridae).
AB  - The ParaHox cluster is the evolutionary sister to the Hox cluster. Like the Hox
      cluster, the ParaHox cluster displays spatial and temporal regulation of the
      component genes along the anterior/posterior axis in a manner that correlates
      with the gene positions within the cluster (a feature called collinearity). The
      ParaHox cluster is however a simpler system to study because it is composed of
      only three genes. We provide a detailed analysis of the amphioxus ParaHox cluster
      and, for the first time in a single species, examine the regulation of the
      cluster in response to a single developmental signalling molecule, retinoic acid
      (RA). Embryos treated with either RA or RA antagonist display altered ParaHox
      gene expression: AmphiGsx expression shifts in the neural tube, and the
      endodermal boundary between AmphiXlox and AmphiCdx shifts its anterior/posterior
      position. We identified several putative retinoic acid response elements and in
      vitro assays suggest some may participate in RA regulation of the ParaHox genes.
      By comparison to vertebrate ParaHox gene regulation we explore the evolutionary
      implications. This work highlights how insights into the regulation and evolution
      of more complex vertebrate arrangements can be obtained through studies of a
      simpler, unduplicated amphioxus gene cluster.

PMID- 19103192
TI  - Combined informatic and expression screen identifies the novel DAF-16 target HLH
      13.
AB  - Insulin/IGF-signaling (IIS) affects longevity, stress resistance and metabolism
      in worms, flies, and mammals. The Forkhead transcription factor DAF-16/FOXO is
      the major downstream effector of IIS and is responsible for the activation and
      repression of genes that mediate the diverse effects of IIS. We surveyed a set of
      informatically predicted conserved DAF-16/FOXO target genes and identified the
      novel DAF-16 direct target hlh-13. hlh-13 is the predicted homolog of the
      mammalian transcription factor Ptf1a, a critical determinant of pancreatic
      development. We found that an hlh-13 mutant exits L1 arrest and IIS-dependent
      dauer diapause faster than control worms, but is not involved in lifespan or
      resistance to a variety of stresses. Our results have identified a novel DAF-16
      target gene and linked its function to known outputs of IIS. Considering the high
      conservation of IIS in diverse species, our results also hint at an intriguing
      connection of IIS and Ptf1a in mammals.

PMID- 19103193
TI  - Mouse Shh is required for prechordal plate maintenance during brain and
      craniofacial morphogenesis.
AB  - In humans, holoprosencephaly (HPE) is a common birth defect characterized by the
      absence of midline cells from brain, facial, and oral structures. To understand
      the pathoetiology of HPE, we investigated the involvement of mammalian prechordal
      plate (PrCP) cells in HPE pathogenesis and the requirement of the secreted
      protein sonic hedgehog (Shh) in PrCP development. We show using rat PrCP lesion
      experiments and DiI labeling that PrCP cells are essential for midline
      development of the forebrain, foregut endoderm, and ventral cranial mesoderm in
      mammals. We demonstrate that PrCP cells do not develop into ventral cranial
      mesoderm in Shh(-/-) embryos. Using Shh(-/-) and chimeric embryos we show that
      Shh signal is required for the maintenance of PrCP cells in a non-cell autonomous
      manner. In addition, the hedgehog (HH)-responding cells that normally appear
      during PrCP development to contribute to midline tissues, do not develop in the
      absence of Shh signaling. This suggests that Shh protein secreted from PrCP cells
      induces the differentiation of HH-responding cells into midline cells. In the
      present study, we show that the maintenance of a viable population of PrCP cells
      by Shh signal is an essential process in development of the midline of the brain
      and craniofacial structures. These findings provide new insight into the
      mechanism underlying HPE pathoetiology during dynamic brain and craniofacial
      morphogenesis.

PMID- 19103194
TI  - Protection from DNBS-induced colitis by the tachykinin NK(1) receptor antagonist
      SR140333 in rats.
AB  - Inflammation is known to be associated with changes in tachykinin expression both
      in human and animal models: substance P and NK(1) receptor expression are
      increased in patients with inflammatory bowel disease, and similar changes are
      reported in experimental models of inflammation. We investigated the effect of
      the tachykinin NK(1) receptor antagonist SR140333 (10 mg/kg orally) on 2,4
      dinitrobenzene sulfonic acid (DNBS)-induced colitis in rats. Colonic damage was
      assessed by means of macroscopic and microscopic scores, myeloperoxidase activity
      (MPO) and TNF-alpha tissue levels on day 6 after induction of colitis. An enzyme
      immunoassay technique was used to measure colonic substance P levels. DNBS
      administration impaired body weight gain and markedly increased all inflammatory
      parameters as well as colonic tissue levels of substance P. Treatment with
      SR140333 significantly counteracted the impairment in body weight gain, decreased
      macroscopic and histological scores and reduced colonic myeloperoxidase activity
      and TNF-alpha tissue levels. Colonic tissue levels of substance P were also
      reduced by SR140333, although this effect did not reach statistical significance.
      In conclusion, treatment with SR140333 protects from DNBS-induced colitis in
      rats. These results suggest a role for NK(1) receptors and substance P in the
      development of intestinal inflammation and indicate tachykinin receptors as a
      potential pharmacological target in the treatment of inflammatory bowel disease.

PMID- 19103195
TI  - An alpha4beta1 integrin antagonist decreases airway inflammation in ovalbumin
      exposed mice.
AB  - Inhibition of the alpha4 subunit of both the alpha4beta1 and alpha4beta7
      integrins has shown promise in decreasing airway inflammation and airway
      hyperresponsiveness in various animal models. We hypothesized that a novel, high
      affinity alpha4beta1 antagonist (LLP2A) would decrease the migration of
      eosinophils to the lung and ameliorate the airway hyperresponsiveness in a mouse
      model of ovalbumin-induced airway inflammation. To test this hypothesis, we
      administered LLP2A, or scrambled LLP2A (a negative control), prior to exposure of
      sensitized BALB/c mice to ovalbumin aerosol. We can partially prevent, or
      reverse, the airway inflammatory response, but not airways hyperresponsiveness,
      by treatment of mice with LLP2A, a synthetic peptidomimetic alpha4beta1
      antagonist. Specifically engineered, PEGylated (PEG) formulations of this
      antagonist further reduce the airway inflammatory response to ovalbumin,
      presumably by improving the circulating half-life of the drug.

PMID- 19103196
TI  - High frequencies of short alleles of NOS1 (CA)n polymorphism in beta(0)39
      carriers from Corsica Island (France).
AB  - In this work we investigated about the presence of a correlation between a (CA)n
      repeat located in exon 29 of NOS1 gene and the beta-thalassemia trait in Corsica
      Island (France). We genotyped a sample of individuals with beta-thalassemia minor
      (N=110) and an ethnically matched control (N=113) from Balagna, a region of
      Corsica Island (France). Results highlighted the high frequencies of allele with
      16 and 17 repeats in the thalassemic sample. From these results we suggest, that
      high frequencies of alleles with 16 and 17 repeats, could be a consequence of
      past malarial endemicity.

PMID- 19103198
TI  - Upregulation and maintenance of gap junctional communication in lens cells.
AB  - The cells of the lens are joined by an extensive network of gap junction
      intercellular channels consisting of connexins 43, 46, and 50. We have proposed,
      and experimentally supported, the hypothesis that fibroblast growth factor (FGF)
      signaling is required for upregulation of gap junction-mediated intercellular
      coupling (GJIC) at the lens equator. The ability of FGF to increase GJIC in
      cultured lens cells requires sustained activation of extracellular signal
      regulated kinase (ERK). In other cell types, activation of ERK has been shown to
      block GJIC mediated by connexin43 (Cx43). Why ERK signaling does not block lens
      cell coupling is not known. Another unresolved issue in lens gap junction
      regulation is how connexins, synthesized before the loss of biosynthetic
      organelles in mature lens fiber cells, avoid degradation during formation of the
      organelle-free zone. We have addressed these questions using serum-free cultures
      (termed DCDMLs) of primary embryonic chick lens epithelial cells. We show that
      FGF stimulates ERK in DCDMLs via the canonical Ras/Raf1 pathway, and that the
      reason that neither basal nor growth factor-stimulated GJIC is blocked by
      activation of ERK is because it is not mediated by Cx43. In fibroblastic cells,
      the normally rapid rate of degradation of Cx43 after its transport to the plasma
      membrane is reduced by treatments that either directly (ALLN; epoxomicin) or
      indirectly (generation of oxidatively un/mis-folded proteins by arsenic
      compounds) prevent the ubiquitin/proteasome system (UPS) from acting on its
      normal substrates. We show here that Cx45.6 and Cx56, the chick orthologs of
      mammalian Cx50 and Cx46, behave similarly in DCDMLs. When organelles lyse during
      the maturation of fiber cells, they release into the cytosol a large amount of
      new proteins that have the potential to saturate the capacity, and/or compromise
      the function, of the UPS. This would serve to spare gap junctions from
      degradation during formation of the organelle-free zone, thereby preserving GJIC
      between mature fiber cells despite the lack of de novo connexin synthesis.

PMID- 19103197
TI  - The changing paradigm of outflow resistance generation: towards synergistic
      models of the JCT and inner wall endothelium.
AB  - Aqueous humor outflow resistance is the primary determinant of intraocular
      pressure (IOP), and increased outflow resistance is the basis for elevated IOP
      associated with glaucoma. Experimental evidence suggests that the bulk of outflow
      resistance is generated in the vicinity of the inner wall endothelium of
      Schlemm's canal, its basement membrane and the juxtacanalicular connective tissue
      (JCT). However, attempts to sort out the contribution of each of these tissues to
      total outflow resistance have not been successful. Conventional understanding of
      outflow resistance assumes that the resistance of each tissue strata (i.e., the
      inner wall endothelium, its basement membrane and JCT) in the outflow pathway
      adds in series to contribute to total outflow resistance generation. However,
      this perspective leads to a paradox where the apparent resistances of all tissues
      in the outflow pathway are much lower than the measured total resistance. To
      resolve this paradox, we explore synergistic models of outflow resistance
      generation where hydrodynamic interactions between different tissue strata lead
      to a total resistance that is greater than the sum of the individual tissue
      resistances. We closely examine the "funneling" hypothesis that has emerged as a
      leading synergistic model, and we review the basis of funneling, mechanical and
      biological requirements for funneling and evidence in support of this hypothesis.
      We also propose refinements to the funneling model and describe how funneling may
      relate to segmental variability of aqueous humor outflow patterns observed within
      the trabecular meshwork. Pressure gradients across the JCT and inner wall
      endothelium will generate mechanical loads that influence the morphology of these
      tissues. Because tissue morphology may in turn affect outflow resistance, there
      exists the potential for a two-way coupling or a "fluid-solid interaction"
      between outflow hydrodynamics and the mechanical behavior of the inner wall and
      JCT. Furthermore, the adhesions and tethers between the inner wall and JCT must
      be physically capable of supporting such loads. We examine the structure and
      mechanical strength of these adhesions, and provide evidence that these adhesions
      and tethers are unable to support the full load imposed by the bulk of outflow
      resistance generation unless a substantial fraction of outflow resistance is
      generated within the JCT, consistent with the funneling model. This indicates
      that these attachments between the inner wall and JCT have considerable
      physiological importance for outflow resistance regulation, by maintaining the
      proximity between these two tissues to facilitate funneling. Further study is
      greatly needed to better characterize these important interactions.

PMID- 19103199
TI  - Differential gene expressions in the lacrimal gland during development and onset
      of keratoconjunctivitis sicca in Sjogren's syndrome (SJS)-like disease of the
      C57BL/6.NOD-Aec1Aec2 mouse.
AB  - Recently, we reported development of the C57BL/6.NOD-Aec1Aec2 mouse carrying two
      genetic intervals derived from the NOD mouse. These two genetic regions confer
      Sjogren's syndrome (SjS)-like disease in SjS-non-susceptible C57BL/6 mice. In an
      attempt to define the molecular bases underlying onset of dacryoadenitis and
      subsequently keratoconjunctivitis sicca (or xerophthalmia) in the C57BL/6.NOD
      Aec1Aec2 mouse model, we have carried out a study utilizing microarray
      technology. Using oligonucleotide microarrays, gene expression profiles of
      lacrimal glands at 4, 8, 12, 16 and 20weeks of age were generated for C57BL/6.NOD
      Aec1Aec2 male mice. Analyses using Linear Models for Microarray Analysis package
      and B-statistics, 552 genes were identified as being differentially expressed
      (adjusted p-value <0.01 and B <1.5) during the development of SjS-like disease.
      These 552 genes could be arranged into four clusters, with each cluster defining
      a unique pattern of temporal expression, while the individual genes within each
      cluster could be grouped according to related function. Using a pair-wise
      analysis, temporal changes in gene expressions provided profiles indicating that
      individual genes were differentially expressed at specific time points during
      development of SjS. In addition, multiple genes that have been reported to show,
      either in humans or mouse models, an association with autoimmunity and/or SjS,
      e.g., ApoE, Baff, Clu, Ctla4, Fas/Fasl, Irf5, Lyzs, Nfkb, Socs3, Stat4, Tap2,
      Tgfbeta1, Tnfa, and Vcam1 were also found to exhibit differential expressions,
      both quantitatively and temporally. Selecting a few families of genes, e.g.,
      cystatins, cathepsins, metalloproteinases, lipocalins, complement, kallikreins,
      carbonic anhydrases and tumor necrosis factors, it was noted that only a limited
      number of family members showed differential expressions, suggesting a restricted
      glandular expression. Utilizing these genes, pathways of inter-reactive genes
      have been constructed for apoptosis and fatty acid homeostasis, leading to
      modeling of possible underlying events inducing disease. Thus, these different
      approaches to analyze microarray data permit identification of multiple sets of
      genes of interest whose expressions and expression profiles may correlate with
      molecular mechanisms, signaling pathways and/or immunological processes involved
      in the development and onset of SjS in this mouse model, thereby providing new
      insight into the underlying cause or regulation of this disease.

PMID- 19103201
TI  - The gut microbiota: a microbial arsenal protecting us from infectious and
      radiation-induced diarrhea.

PMID- 19103200
TI  - The structure of the cytoplasm of lens fibers as determined by conical
      tomography.
AB  - Studies using conventional electron microscopy describe the cytoplasm of lens
      fiber cells as having essentially an amorphous structure. We hypothesized that
      significant structural detail might have been lost as a result of projecting the
      entire thickness of the section (50-100 nm) onto a single plane (the "projection
      artifact"). To test this hypothesis, we studied the 3D-structure of rat lens
      cortical fibers before and after extracting the "soluble" crystallins with low
      ionic strength buffers to make "ghosts." Tomographic series in conical geometry
      were collected at 55 degrees tilts and by 5 degrees rotations until completing a
      360 degrees turn by low dose methods. They were aligned using fiduciary points,
      reconstructed with the weighted back projection algorithm and refined by
      projection matching. Analysis of the 3D-maps included semiautomatic density
      segmentation using a computer program based on the watershed algorithm. We found
      that the cytoplasm of cortical fibers, though appearing amorphous in regions of
      the highest density, was in fact comprised of an ordered structure resembling a
      "clustered matrix." The matrix was comprised of thin ( approximately 6 nm
      diameter) filaments bent sharply at 110-120 degrees angles and studded with cube
      shaped particles (the "beaded" filaments). In cortical fibers, the particles
      measured a=14+/-2, b=13+/-2 and c=10+/-2.4 nm (n=30, mean+/-SD) and were spaced
      at distances measuring 27.5+/-2.4 nm apart (n=8, mean+/-SD), center-to-center.
      The matrix was formed as "beaded" filaments, bound to clusters of "soluble"
      proteins, crossed each other at nearly perpendicular angles. The matrix also made
      contact with the plasma membrane at a large number of distinct regions. We thus
      concluded that the cytoplasm of cortical lens fibers is comprised of a
      cytoskeletal matrix of "beaded" filaments that organize the "soluble" crystallins
      in separate regions. The association of this matrix with the plasma membrane
      allows the lens to maintain its structural integrity, while its association with
      crystallins yields its long-term transparency. Loss of either function likely
      would play a significant role in cataract formation.

PMID- 19103203
TI  - Clonality, founder mutations, and field cancerization in human ulcerative colitis
      associated neoplasia.
AB  - BACKGROUND & AIMS: The clonality of colitis-associated neoplasia has not been
      fully determined. One previous report showed polyclonal origins with subsequent
      monoclonal outgrowth. We aimed to assess the clonality and mutation burden of
      individual crypts in colitis-associated neoplasias to try to identify gatekeeping
      founder mutations, and explore the clonality of synchronous lesions to look for
      field effects. METHODS: Individual crypts (range, 8-21 crypts) were
      microdissected from across 17 lesions from 10 patients. Individual crypt
      adenomatous polyposis coli (APC), p53, K-RAS, and 17p loss of heterozygosity
      mutation burden was established using polymerase chain reaction and sequencing
      analysis. Serial sections underwent immunostaining for p53, beta-catenin, and
      image cytometry to detect aneuploidy. RESULTS: In most lesions an oncogenic
      mutation could be identified in all crypts across the lesion showing
      monoclonality. This founder mutation was a p53 lesion in the majority of
      neoplasms but 4 tumors had an initiating K-RAS mutation. Some nondysplastic
      crypts surrounding areas of dysplasia were found to contain clonal p53 mutations
      and in one case 3 clonal tumors arose from a patch of nondysplastic crypts
      containing a K-RAS mutation. CONCLUSIONS: This study used mutation burden
      analysis of individual crypts across colitis-associated neoplasms to show lesion
      monoclonality. This study confirmed p53 mutation as initiating mutation in the
      majority of lesions, but also identified K-RAS activation as an alternative
      gatekeeping mutation. Local and segmental field cancerization was found by
      showing pro-oncogenic mutations in nondysplastic crypts surrounding neoplasms,
      although field changes are unlikely to involve the entire colon because widely
      separated tumors were genetically distinct.

PMID- 19103204
TI  - Physiologic and cardiac roles of beta-arrestins.
AB  - Beta-arrestin1 and beta-arrestin2 were initially identified by sequence homology
      to visual arrestins and by their ability to bind to and inactivate signaling of
      the beta-2-adrenergic receptor in a process known as desensitization. While the
      role of beta-arrestins in desensitization has been known for some time, more
      recent evidence has revealed that beta-arrestins are multifunctional scaffolding
      proteins that are involved in numerous aspects of G protein-coupled receptor
      (GPCR) signaling. Interestingly, exciting new data shows that beta-arrestins can
      mediate signaling in their own right independent of classical second messenger
      mediated signaling, and that this beta-arrestin-mediated signaling may be
      cardioprotective. Identifying novel ligands for GPCRs that can block G protein
      mediated signaling while simultaneously promoting beta-arrestin-mediated
      signaling could provide powerful new therapies for cardiac disease.

PMID- 19103205
TI  - Structural insights into the association between BCAR3 and Cas family members, an
      atypical complex implicated in anti-oestrogen resistance.
AB  - The association between novel Src homology 2-containing protein (NSP) and Crk
      associated substrate (Cas) family members contributes to integrin and receptor
      tyrosine kinase signalling and is involved in conferring anti-oestrogen
      resistance to human breast carcinomas. The precise role of this association in
      tumorigenesis remains controversial, and the molecular basis for the complex NSP
      and Cas protein form is unknown. Here we present a pluridisciplinary approach,
      including small-angle X-ray scattering, that provides first insights into the
      structure of the complex formed between breast cancer anti-oestrogen resistance 3
      (BCAR3, an NSP family member) and human enhancer of filamentation 1 (HEF1, also
      named NEDD9 or Cas-L, a Cas family protein). Our analysis corroborates a four
      helix bundle structure for the NSP-binding domain of HEF1 and a Cdc25-like
      guanine nucleotide exchange factor (GEF) fold for the Cas-binding domain of
      BCAR3. Using residues located on helix 2 of the four-helix bundle, HEF1 binds
      very tightly to a site on BCAR3 that is remote from the putative guanosine
      triphosphatase binding site of the GEF domain, but similar to a site implicated
      in allosteric regulation of the homologous SOS (Son of Sevenless) GEF domain.
      Thus, the association between NSP and Cas proteins might not only create a very
      stable link between these molecules, co-localising their cellular functions, but
      also modulate the function of the NSP GEF domains. Such modulation may explain,
      at least in part, the controversial results published for NSP GEF function.

PMID- 19103206
TI  - Structural basis of heme binding in the Cu,Zn superoxide dismutase from
      Haemophilus ducreyi.
AB  - The Cu,Zn superoxide dismutase from Haemophilus ducreyi is characterized by the
      unique ability to bind heme at its dimer interface. Here we report the high
      resolution crystal structures of this protein in the heme-loaded (holo) and heme
      free (apo) forms. Heme is asymmetrically bound between the two enzyme subunits,
      where heme iron is coordinated by two histidine residues, His64 and His 124,
      provided by the two subunits. Moreover, the binding of heme to the protein is
      ensured by stabilizing contacts between the prosthetic group and a limited number
      of other residues, most of which are not present in other bacterial enzyme
      variants. We show that the introduction of only three mutations at the dimer
      interface of the enzyme from Haemophilus parainfluenzae, a closely related
      bacterial species, is sufficient to induce heme-binding ability by this enzyme
      variant. Heme binding does not alter protein activity. Moreover, the binding of
      the prosthetic group does not induce any significant structural perturbation at
      the subunit level and requires only limited local structural rearrangements that
      widen the cleft at the dimer interface and cause a limited shift in the relative
      orientation between the subunits. The presence of a preformed heme-binding pocket
      and the significant solvent exposure of the cofactor to the solvent are
      compatible with the suggested protective role of the enzyme against heme toxicity
      or with its involvement in heme trafficking in the periplasmic space.

PMID- 19103207
TI  - Molecular modeling of human BAD and its interaction with PKAc or PP1c.
AB  - To build up the structure of human BAD (Bcl-2 antagonist of cell death),
      subsequently combined with PKAc or PP1c (protein phosphatase 1), to investigate
      the interaction relationship between BAD and its kinase/PTPese at the molecular
      level. Additionally, it is concerned with the search for all optimal positions
      and orientations of a set of amino acid residues of BAD, while its binding sites
      include N-termini (Glu19, Ala27, and Ser34-Lys35), BH3-located helical domain
      (Arg98-Lys126), and C-termini (Trp154-Ser163 and Ser167-Gln168). The related
      sites of PKAc are mainly assembled in C-terminal alpha/beta-domain of PKAc, which
      comprises the KTL motif (47-49), Glu203 residue, a helical region (Asp241
      Arg256), and the span from 328 to 333; while the interaction sites with BAD
      converge at C-terminal beta-domain of PP1c, which includes the DEK motif (166
      168), the stretch from 179 to 197 including a helix (Glu184-Arg188), Glu230
      Asp242 segment containing Val232-His237 helix, and Glu287-Leu289 loop. In
      conclusion, analysis of the complex between BAD and PKAc or PP1c provides a novel
      viewpoint on the structural origins of molecular recognition. And the complex
      models suggest that BH3 domain of BAD interact with PKAc or PP1c by
      electrostatic, van der Waals contacts, hydrogen bond and salt bridge. This is
      helpful for our development and research of some new drugs, especially mimetic
      BH3 peptides and inspires scientists with BAD complex and molecular mechanism of
      its integrating glycolysis and apoptosis.

PMID- 19103208
TI  - HIV-1 gp120 induces cytokine expression, leukocyte adhesion, and transmigration
      across the blood-brain barrier: modulatory effects of STAT1 signaling.
AB  - How neuroinflammatory activities affect signaling pathways leading to blood-brain
      barrier (BBB) injury during HIV/AIDS are currently unknown. Our previous work
      demonstrated that HIV-1 exposure activates pro-inflammatory genes in human brain
      microvascular endothelial cells (HBMEC) and showed that these genes are linked to
      the janus kinase (JAK)/signal transducers and activators of transcription (STAT)
      pathway. Here, we report that HIV-1 gp120 protein activated STAT1 and induced
      interleukin (IL)-6 and IL-8 secretion in HBMEC. IL-6, IL-8, and gp120 increased
      monocyte adhesion and migration across in vitro BBB models. The STAT1 inhibitor,
      fludarabine, prevented gp120-induced IL-6 and IL-8 secretion. Inhibitors of
      STAT1, mitogen activated protein kinase kinase (MEK) (PD98059), and phosphatidyl
      inositol 3 kinase (PI3K) (LY294002), blocked gp120-induced STAT1 activation and
      significantly diminished IL-8-, IL-6-, and gp120-induced monocyte adhesion and
      migration across in vitro BBB models. These data support the notion that STAT1
      plays an important role in gp120-induced inflammation and BBB dysfunction
      associated with viral infection. Results also suggest crosstalk between STAT1,
      MEK, and PI3K pathways in gp120-induced BBB dysfunction. Inhibition of STAT1
      activation could provide a unique therapeutic strategy to decrease
      neuroinflammation and BBB dysfunction in HIV/AIDS.

PMID- 19103209
TI  - A novel splice site mutation in the dentin sialophosphoprotein gene in a Chinese
      family with dentinogenesis imperfecta type II.
AB  - Twenty-four individuals were investigated that spanned six generations in a
      Chinese family affected with an apparently autosomal dominant form of
      dentinogenesis imperfecta type II (DGI-II, OMIM #125490). All affected
      individuals presented with typical, clinical and radiographic features of DGI-II,
      but without bilateral progressive high-frequency sensorineural hearing loss. To
      investigate the mutated molecule, a positional candidate approach was used to
      determine the mutated gene in this family. Genomic DNA was obtained from 24
      affected individuals, 18 unaffected relatives of the family and 50 controls.
      Haplotype analysis was performed using leukocyte DNA for 6 short tandem repeat
      (STR) markers present in chromosome 4 (D4S1534, GATA62A11, DSPP, DMP1, SPP1 and
      D4S1563). In the critical region between D4S1534 and DMP1, the dentin
      sialophosphoprotein (DSPP) gene (OMIM *125485) was considered as the strongest
      candidate gene. The first four exons and exon/intron boundaries of the gene were
      analyzed using DNA from 24 affected individuals and 18 unaffected relatives of
      the same family. DNA sequencing revealed a heterozygous deletion mutation in
      intron 2 (at positions -3 to -25), which resulted in a frameshift mutation, that
      changed the acceptor site sequence from CAG to AAG (IVS2-3C-->A) and may also
      have disrupted the branch point consensus sequence in intron 2. The mutation was
      found in the 24 affected individuals, but not in the 18 unaffected relatives and
      50 controls. The deletion was identified by allele-specific sequencing and
      denaturing high-performance liquid chromatography (DHPLC) analysis. We conclude
      that the heterozygous deletion mutation contributed to the pathogenesis of DGI
      II.

PMID- 19103210
TI  - The roles of nerve growth factor and cholecystokinin in the enhancement of
      morphine analgesia in a rodent model of central nervous system inflammation.
AB  - Animal models of inflammatory pain are characterized by the release of
      inflammatory mediators such as cytokines and neurotrophic factors, and enhanced
      analgesic sensitivity to opioids. In this study, we examine the mechanisms
      underlying this effect, in particular the roles of cholecystokinin (CCK) and
      nerve growth factor (NGF), in an animal model of central nervous system (CNS)
      inflammation induced by spinal administration of lipopolysaccharide (LPS).
      Although spinal administration of LY-225910 (25 ng), a CCK-B antagonist, enhanced
      morphine analgesia in naive rats, it was unable to do so in LPS-treated animals.
      Conversely, spinal CCK-8S administration (1 ng) decreased morphine analgesia in
      LPS-treated rats, but not in naive animals. Further, spinal anti-NGF (3 microg)
      was able to reduce morphine analgesia in LPS-treated rats, but not in naive
      animals, an effect that was reversed by spinal administration of LY-225910. While
      CCK-8S concentration was increased in spinal cord extracts of LPS animals as
      compared to controls, morphine-induced spinal CCK release in the extracellular
      space, as measured by in-vivo spinal cord microdialysis was inhibited in LPS
      animals as compared to controls, and this was reversed by anti-NGF pretreatment.
      Finally, chronic spinal administration of beta-NGF (7 microg/day) for 7 days
      enhanced spinal morphine analgesia, possibly by mimicking a CNS inflammatory
      state. We suggest that in intrathecally LPS-treated rats, spinal CCK release is
      altered resulting in enhanced morphine analgesia, and that this mechanism may be
      regulated to an important extent by NGF.

PMID- 19103211
TI  - Individual differences in amphetamine sensitization, behavior and central
      monoamines.
AB  - Repeated amphetamine treatment results in behavioral sensitization in a high
      percentage of rats. Alterations to plasma corticosterone, neural monoamines and
      stress behavior can accompany amphetamine sensitization. Whether these changes
      occur following repeated amphetamine treatment in the absence of behavioral
      sensitization is not known. Male Sprague-Dawley rats were treated with
      amphetamine (2.5 mg/kg, i.p.) or saline once daily for 6 days. Amphetamine
      induced locomotion and stereotypy, open-field anxiety behavior, plasma
      corticosterone and limbic monoamines were measured during withdrawal. Sixty-two
      percent of amphetamine-treated rats showed behavioral sensitization over the test
      periods. Only amphetamine-sensitized rats showed increased latency to enter the
      center of the open-field, as well as increased plasma corticosterone when
      compared to saline-treated controls. Amphetamine-sensitized rats showed increased
      dopamine concentrations in the shell of the nucleus accumbens and increased
      serotonin concentrations in the dorsal hippocampus, which were not observed in
      amphetamine-treated non-sensitized rats. These findings suggest that anxiety
      behavior, plasma corticosterone and limbic monoamines concentrations are altered
      by repeated amphetamine (2.5 mg/kg) treatment, and that these neuroendocrine and
      behavioral changes are often associated with sensitization to the psychostimulant
      effects of amphetamine.

PMID- 19103212
TI  - ent-Steroids: novel tools for studies of signaling pathways.
AB  - Membrane receptors are often modulated by steroids and it is necessary to
      distinguish the effects of steroids at these receptors from effects occurring at
      nuclear receptors. Additionally, it may also be mechanistically important to
      distinguish between direct effects caused by binding of steroids to membrane
      receptors and indirect effects on membrane receptor function caused by steroid
      perturbation of the membrane containing the receptor. In this regard, ent
      steroids, the mirror images of naturally occurring steroids, are novel tools for
      distinguishing between these various actions of steroids. The review provides a
      background for understanding the different actions that can be expected of
      steroids and ent-steroids in biological systems, references for the preparation
      of ent-steroids, a short discussion about relevant forms of stereoisomerism and
      the requirements that need to be fulfilled for the interaction between two
      molecules to be enantioselective. The review then summarizes results of
      biophysical, biochemical and pharmacological studies published since 1992 in
      which ent-steroids have been used to investigate the actions of steroids in
      membranes and/or receptor-mediated signaling pathways.

PMID- 19103213
TI  - Evaluations of the trans-sulfuration pathway in multiple liver toxicity studies.
AB  - Drug-induced liver injury has been associated with the generation of reactive
      metabolites, which are primarily detoxified via glutathione conjugation. In this
      study, it was hypothesized that molecules involved in the synthesis of
      glutathione would be diminished to replenish the glutathione depleted through
      conjugation reactions. Since S-adenosylmethionine (SAMe) is the primary source of
      the sulfur atom in glutathione, UPLC/MS and NMR were used to evaluate metabolites
      involved with the transulfuration pathway in urine samples collected during
      studies of eight liver toxic compounds in Sprague-Dawley rats. Urinary levels of
      creatine were increased on day 1 or day 2 in 8 high dose liver toxicity studies.
      Taurine concentration in urine was increased in only 3 of 8 liver toxicity
      studies while SAMe was found to be reduced in 4 of 5 liver toxicity studies. To
      further validate the results from the metabonomic studies, microarray data from
      rat liver samples following treatment with acetaminophen was obtained from the
      Gene Expression Omnibus (GEO) database. Some genes involved in the trans
      sulfuration pathway, including guanidinoacetate N-methyltransferase, glycine N
      methyltransferase, betaine-homocysteine methyltransferase and cysteine
      dioxygenase were found to be significantly decreased while methionine adenosyl
      transferase II, alpha increased at 24 h post-dosing, which is consistent with the
      SAMe and creatine findings. The metabolic and transcriptomic results show that
      the trans-sulfuration pathway from SAMe to glutathione was disturbed due to the
      administration of heptatotoxicants.

PMID- 19103214
TI  - Treatment of focal dystonias with botulinum neurotoxin.
AB  - This is a review on the use of injections of botulinum toxin for the treatment of
      focal dystonias. Disorders covered include cranial dystonia, cervical dystonia,
      spasmodic dysphonia, and focal hand dystonia. Considered are clinical aspects,
      alternative treatment strategies and principles of use of botulinum toxin
      injections.

PMID- 19103215
TI  - Intraspecific variation in the Egyptian scorpion Scorpio maurus palmatus venom
      collected from different biotopes.
AB  - The present study was conducted to explore the following hypotheses: (i) do
      scorpions (Scorpio maurus palmatus) from different biotopes exhibit intraspecific
      diversity in their venom? (ii) if so, is this variation associated with
      ecological or genetic factors, geographical distance, and/or multiple
      interrelated parameters? To address these questions, scorpions were collected
      from four geographically isolated localities in Egypt. Three of these locations
      are from mutually isolated pockets in the arid biotope of Southern Sinai (Wadi
      Sahab, El-Agramia and Rahaba plains). The fourth population was sampled from the
      semiarid biotope of Western Mediterranean Costal Desert (WMCD). Using reducing
      gel electrophoresis (SDS-PAGE), we have shown biotope-specific variation in the
      expression of peptides from scorpions collected from these distinct areas. WMCD
      sourced venom samples contain higher molecular weight protein components (219,
      200, 170, 139, 116 kDa) than Southern Sinai scorpion venom samples. The Southern
      Sinai venom is characterized by the presence of 11 protein bands (93-0.58 kDa)
      that are not mirrored in the individual venom samples of WMCD. Bands of 33 and
      3.4 kDa were characteristics of all individual venom samples of the scorpion
      populations. Even within Southern Sinai area, Sahab venom contains five fractions
      that are not detected in both El-Agramia and Rahaba venom samples. Moreover, male
      and female venom analysis revealed some sex-related proteomic similarities and
      differences between scorpion populations. Female venom appears to be more
      complicated than the male venom. Female venom samples showed bands of 219, 200,
      77.5, 55.5, 45, 39, 37, 24 and 16 kDa which were absent in the male venom. The
      random amplified polymorphic DNA (RAPD) technique was used to estimate the
      genetic distance between the four scorpion populations. The RAPD data confirmed
      the genetic diversity at molecular level among the sampled populations. More than
      77 RAPD bands (ranging in size from 125 to 15,000 bp) were defined from the four
      scorpion populations. Of the 77 bands, 57 (76.2%) were polymorphic and 20 were
      monomorphic among the populations. The similarity coefficient data of venom and
      DNA were used to construct separate dendrograms, which grouped together the
      Southern Sinai populations and these were some distance away from the WMCD
      population. Taken together, we suspect that a combination of local environmental
      conditions, geographical separation and genetic separation may play a major role
      in the intraspecific variation of venom of S. m. palmatus.

PMID- 19103216
TI  - Mechanisms involved in the rat peritoneal leukocyte migration induced by a Kunitz
      type inhibitor isolated from Dimorphandra mollis seeds.
AB  - DMTI-II is a Kunitz-type inhibitor isolated from Dimorphandra mollis seeds that
      causes rat inflammatory edema by mechanisms involving activation of mast cells
      and sensory C-fibers. The present study aimed to further explore the inflammatory
      mechanisms involved in DMTI-II-induced inflammation, focusing to the leukocyte
      migration in vivo. Male Wistar rats (250-280 g) were injected with DMTI-II (1
      100microg/cavity), and at 4-24h thereafter the leukocyte counts in peritoneal
      lavage were evaluated. DMTI-II caused dose- and time-dependent accumulation of
      neutrophils and eosinophils. The peritoneal neutrophil influx initiated at 4h,
      achieving maximal responses at 16 h after DMTI-II injection (16- and 22-fold
      increase, respectively). The DMTI-II-induced eosinophil recruitment was observed
      as early as 4h achieving the maximal responses at 16 h (12- and 17-fold increase,
      respectively). The mononuclear cell number increased at 4h and 16 h (1.5-fold and
      1.6-increase, respectively). Prior treatments with dexamethasone, the
      cyclooxygenase (COX) inhibitors indomethacin and celecoxib, as well as the PAF
      receptor antagonist PCA4248 largely reduced the neutrophil and eosinophil
      accumulation. The selective lypoxygenase inhibitor AA861, the tachykinin NK(1)
      antagonist SR-140333 and the nitric oxide inhibitor L-NAME reduced only the
      eosinophil number. The eotaxin levels were significantly higher in DMTI-II
      injected rats compared with control animals. In conclusion, DMTI-II causes an
      early migration of eosinophils and neutrophils by mechanisms involving COX-2- and
      lipoxygenase-derived metabolites, PAF, substance P and NO. The capacity of DMTI
      II to recruit eosinophils at early times is likely to reflect the allergen
      properties of proteinase inhibitors belonging to Kunitz family.

PMID- 19103217
TI  - Common-fate motion processing: interaction of the On and Off pathways.
AB  - The processing of common-fate (motion-defined-form) signals was investigated
      using a modified version of the global dot-motion stimulus. The primary aim of
      the studies was to determine whether such stimuli could be processed by a form
      specific motion system. This was achieved by investigating the interaction of the
      On and Off pathways in the processing of these stimuli, given that they have been
      shown to be pooled differently by the standard-motion and form systems (pooled
      versus independent, respectively). The number of signal dots was fixed at four
      and the number of noise dots was varied to establish the threshold signal-to
      noise ratio required to determine the direction of the signal dots (up/down). The
      same dots remained signal dots over the three-frame motion sequence. The effect
      of different spatial patterns (square, horizontal line, vertical line, T-shape,
      random shape and no local grouping) and the interaction of contrast-polarity
      information, i.e. the interaction of the On and Off pathways, were investigated.
      To minimise the possibility of attentional tracking of the signal dots, the first
      motion frame contained 12 distracter patterns, i.e. noise dots arranged into the
      same pattern as the signal dots. Results indicate that performance is better for
      certain spatial arrangements than others and that contrast-polarity information
      appears to be pooled independently in the processing of the fixed-geometric
      shapes but not variable-shapes. These results are not due to differences in the
      spatial-frequency content of the stimuli and the use of a two-frame sequence
      ruled out attention-based tracking. This difference in the pooling of the On and
      Off pathways indicates that the different stimuli are processed by different
      systems, with the geometric conditions possibly being processed by a form
      specific system.

PMID- 19103218
TI  - Social memory in mice: disruption with an NMDA antagonist and attenuation with
      antipsychotic drugs.
AB  - Social recognition reflects the ability of one animal to learn and remember the
      identity of another. Animal models of social learning and memory are pertinent to
      several different CNS diseases involving disruptions in cognition. Moreover, the
      increased understanding of the basic biology of memory increases the likelihood
      of discovery of memory-enhancing treatments in these human diseases. In the
      present study, we investigated the effects of the non-competitive NMDA antagonist
      ketamine on social recognition in mice across a broad dose range (5-30 mg/kg) and
      time-course (60 min-7 days). We also tested the ability of two antipsychotic
      drugs, haloperidol and olanzapine, to block the ketamine effect. Our results show
      that mice demonstrate social recognition over a several day period, with loss of
      recognition between 3-7 days. Ketamine disrupts social memory at doses which do
      not affect task performance. Chronic oral administration of haloperidol or
      olanzapine attenuates these ketamine-induced effects on social recognition,
      tending to normalize the memory behavior. The neural mechanisms of these actions
      are not known, although medial temporal lobe memory systems have been implicated.

PMID- 19103219
TI  - Associations between health-related quality of life and smoking status among a
      large sample of U.S. adults.
AB  - OBJECTIVE: To examine the association between self-perceived health-related
      quality of life (HRQoL) and smoking status. METHODS: We used data from 2006
      Behavioral Risk Factor Surveillance System, USA participants in four states
      (n=17,800) to compare the HRQoL of current smokers who unsuccessfully attempted
      to quit (unsuccessful quitters), former smokers, and never smokers with the HRQoL
      of current smokers who made no attempts to quit (non-quitters). RESULTS: Overall,
      unsuccessful quitters were more likely than non-quitters to report frequent
      mental distress, physical distress, and pain but not frequent depressive
      symptoms; former and never smokers were less likely than non-quitters to report
      frequent depressive symptoms. When study subjects were stratified by sex, these
      associations held true for men, but not for women. Among women, the prevalence of
      frequent mental and physical distress among former smokers and never smokers was
      not significantly different from the prevalence among non-quitters, whereas
      unsuccessful quitters were 2.4 times more likely to report frequent mental
      distress and 2.1 times more likely to report frequent physical distress than were
      non-quitters. CONCLUSIONS: Certain HRQoL characteristics were worse among smokers
      who unsuccessfully attempted to quit and better among former smokers than among
      smokers who made no attempts to quit.

PMID- 19103220
TI  - ProPhenolOxidase in Daphnia magna: cDNA sequencing and expression in relation to
      resistance to pathogens.
AB  - Invertebrates utilise the innate immune system when defending against pathogenic
      attack. However, except for some effectors as proPhenolOxidase (proPO), the
      innate immune response is less well understood outside model insect species, and
      its role in natural host-pathogen systems is generally not well documented. We
      have therefore initiated studies on the immune response of the crustacean Daphnia
      when exposed to the specialist endobacterial pathogen, Pasteuria ramosa. This
      study was focused on the proPO gene of Daphnia magna. D. magna possesses a single
      copy of proPO (as does its congener, D. pulex), but there was some evidence of
      alternative splicing. Analyses of sequence similarity in a range of arthropod
      taxa suggested that the proPO gene in Daphnia was as dissimilar to other
      crustaceans as it was to insects, while analysis on intraspecific variation
      indicated that the gene is highly conserved. ProPO was found to be significantly
      up-regulated within 1-4h following exposure to the bacteria. This is the first
      evidence of a Daphnia immune response, and our observations raise the possibility
      that the PhenolOxidase (PO) cascade is involved in the defence against pathogenic
      gram-positive bacteria.

PMID- 19103221
TI  - Mechanisms of pulmonary toxicity and medical applications of carbon nanotubes:
      Two faces of Janus?
AB  - Nanotechnology is an emerging science involving manipulation of materials at the
      nanometer scale. There are several exciting prospects for the application of
      engineered nanomaterials in medicine. However, concerns over adverse and
      unanticipated effects on human health have also been raised. In fact, the same
      properties that make engineered nanomaterials attractive from a technological and
      biomedical perspective could also make these novel materials harmful to human
      health and the environment. Carbon nanotubes are cylinders of one or several
      coaxial graphite layer(s) with a diameter in the order of nanometers, and serve
      as an instructive example of the Janus-like properties of nanomaterials. Numerous
      in vitro and in vivo studies have shown that carbon nanotubes and/or associated
      contaminants or catalytic materials that arise during the production process may
      induce oxidative stress and prominent pulmonary inflammation. Recent studies also
      suggest some similarities between the pathogenic properties of multi-walled
      carbon nanotubes and those of asbestos fibers. On the other hand, carbon
      nanotubes can be readily functionalized and several studies on the use of carbon
      nanotubes as versatile excipients for drug delivery and imaging of disease
      processes have been reported, suggesting that carbon nanotubes may have a place
      in the armamentarium for treatment and monitoring of cancer, infection, and other
      disease conditions. Nanomedicine is an emerging field that holds great promise;
      however, close attention to safety issues is required to ensure that the
      opportunities that carbon nanotubes and other engineered nanoparticles offer can
      be translated into feasible and safe constructs for the treatment of human
      disease.

PMID- 19103222
TI  - Evoked potential variability.
AB  - An unsupervised correlation-based clustering method was developed to assess the
      trial-to-trial variability of auditory evoked potentials (AEPs). The method first
      decomposes single trials into three frequency bands, each containing activity
      primarily associated with one of the three major AEP components, i.e., P50, N100
      and P200. Next, single-trial evoked potentials with similar post-stimulus
      characteristics are clustered and selectively averaged to determine the presence
      or absence of an AEP component. The method was evaluated on actual AEP and
      spontaneous EEG data collected from 25 healthy participants using a paradigm in
      which pairs of identical tones were presented, with the first stimulus (S1)
      presented 0.5s before the second stimulus (S2). Homogeneous, well-separated
      clusters were obtained and substantial AEP variability was found. Also, there was
      a trend for S2 to produce fewer 'complete' (and significantly smaller) responses
      than S1. Tests conducted on spontaneous EEG produced similar clusters as obtained
      from EP data, but significantly fewer stimuli produced responses containing all
      three EP components than seen in AEP data. These findings suggest that the
      clustering method presented here performs adequately to assess trial-to-trial EP
      variability. Also, the results suggest that the sensory gating observed in normal
      controls may be caused by the fact that the second stimulus generates fewer
      'responsive' trials than the first stimulus, thus resulting in smaller ensemble
      averages.

PMID- 19103223
TI  - The correlation between quantitative T2' and regional cerebral blood flow after
      acute brain ischemia in early reperfusion as demonstrated in a middle cerebral
      artery occlusion/reperfusion model of the rat.
AB  - INTRODUCTION: qT2'-maps are calculated by subtracting T2- from T2*-relaxation
      rates. They are oxygen-sensitive and depict oxygen extraction. In several studies
      they have been used to describe the penumbra in patients with acute ischemic
      stroke. No correlation between rCBF and qT2' has been performed to date. In this
      study a correlation between rCBF and qT2' was performed in a temporary middle
      cerebral occlusion-reperfusion model of the rat. MATERIALS AND METHODS: Temporary
      middle cerebral artery occlusion was performed on seven Sprague-Dawley rats.
      After 60 min of occlusion and 90 min of reperfusion MRI was performed including
      DWI, dynamic susceptibility contrast-weighted MR imaging (DSC-MRI) and qT2'. ROIs
      were placed inside the DWI lesion and transferred to rCBF- and qT2'-maps. rCBF
      and qT2' were compared to corresponding tissue in the contralateral hemisphere.
      RESULTS: qT2' was lower in the infarcted areas when compared to the contralateral
      hemisphere. Correlation between rCBF and qT2' was r = 0.41, p = 0.14 (Pearson's
      correlation coefficient), when corrected for outliers it was r = 0.58, p = 0.04.
      CONCLUSION: Our results show that there is a moderate correlation between rCBF
      and qT2'. qT2'-maps could be used to explore cerebral perfusion without the
      application of contrast agent or radiation.

PMID- 19103224
TI  - Purification of DNA from the cell-associated herpesvirus Marek's disease virus
      for 454 pyrosequencing using micrococcal nuclease digestion and polyethylene
      glycol precipitation.
AB  - Methods for the isolation of DNA from cell-associated herpesviruses have often
      yielded samples contaminated with host cellular DNA. Because 2nd and 3rd
      generation nucleotide sequencers do not rely on molecular cloning of viral DNA,
      there is a need to develop methods for isolating highly pure DNA from these
      viruses. The cell-associated alphaherpesvirus Marek's disease virus (MDV-1) was
      chosen as a test virus for the development of such methodologies. The genomes of
      six MDV-1 strains have previously been sequenced using both Sanger dideoxy
      sequencing and 454 Life Sciences pyrosequencing. These genomes largely represent
      cell culture adapted strains due to the difficulty in obtaining large quantities
      of DNA from true low passage isolates. There are clear advantages in analyzing
      MDV-1 virus taken directly from infected tissues or low passage isolates since
      serial passage attenuates the virus. Procedures using an ATP-dependent
      exonuclease and Phi29 DNA polymerase to degrade host DNA selectively and amplify
      MDV-1 DNA enzymatically from total DNA preps were attempted without much success.
      Ultimately, however, a protocol was developed for purification of low passage MDV
      1 DNA from infected avian fibroblasts. The method builds upon and extends
      available protocols based on hypotonic lysis to release virus particles followed
      by micrococcal nuclease treatment to degrade cellular DNA. Intact high-molecular
      weight viral DNA is purified away from an excess of degraded cellular DNA using
      polyethylene glycol precipitation. 454-based pyrosequencing of viral DNA purified
      in this manner has generated data containing as little as 2.3% host sequence. On
      average, DNA preparations were 70% (+/-20%) pure yielding a genome coverage range
      of 25-74-fold.

PMID- 19103225
TI  - Characterization of a continuous feline mammary epithelial cell line susceptible
      to feline epitheliotropic viruses.
AB  - Mucosal epithelial cells are the primary targets for many common viral pathogens
      of cats. Viral infection of epithelia can damage or disrupt the epithelial
      barrier that protects underlying tissues. In vitro cell culture systems are an
      effective means to study how viruses infect and disrupt epithelial barriers,
      however no true continuous or immortalized feline epithelial cell culture lines
      are available. A continuous cell culture of feline mammary epithelial cells (FMEC
      UCD-04-2) that forms tight junctions with high transepithelial electrical
      resistance (>2000Omegacm(-1)) 3-4 days after reaching confluence was
      characterized. In addition, it was shown that FMECs are susceptible to infection
      with feline calicivirus (FCV), feline herpesvirus (FHV-1), feline coronavirus
      (FeCoV), and feline panleukopenia virus (FPV). These cells will be useful for
      studies of feline viral disease and for in vitro studies of feline epithelia.

PMID- 19103226
TI  - Pseudorabies virus glycoprotein B can be used to carry foot and mouth disease
      antigens in DNA vaccination of pigs.
AB  - To evaluate the feasibility of using pseudorabies virus (PrV) glycoprotein B (gB)
      as a carrier of foot and mouth disease virus (FMDV) antigens in DNA immunization,
      FMDV B- and T-cell epitopes were inserted either between the two B-cell epitopes
      of the N-term subunit of PrV-gB (BT-PrV-gB-N-term construct) or within the B-cell
      epitope of the C-term subunit of PrV-gB (BT-PrV-gB-C-term construct). Two animal
      experiments were performed, each with three injections of plasmids 2 weeks apart,
      followed by a booster inoculation of peptides corresponding to the FMDV epitopes.
      Control groups of pigs were injected with plasmids encoding either PrV-gB or FMDV
      BT, or with empty-pcDNA3. The results of both assays were combined. Significant
      titers of FMDV neutralizing antibodies were detected after the peptides boost in
      groups injected with the BT-PrV-gB-C-term construct. Insignificant amounts were
      detected in groups injected with the BT-PrV-gB-N-term and FMDV-BT constructs.
      PBMCs from the BT-PrV-gB-N-term groups, isolated after the peptide boost
      injection, produced IFN-gamma and IL-4 mRNAs in vitro when stimulated with FMDV
      peptides. This was not observed with the other groups. These results imply that
      PrV-gB can be used to carry FMDV antigens in a DNA vaccine.

PMID- 19103227
TI  - Lesion of the ventral and intermediate hippocampus abolishes anticipatory
      activity in the medial prefrontal cortex of the rat.
AB  - The medial prefrontal cortex (mPFC) of the rat receives a prominent input from
      the ventral two thirds of the hippocampus, a structure important for spatial
      awareness, working memory and motivation. We recently found [Hok V, Lenck-Santini
      PP, Roux S, Save E, Muller RU, Poucet B. Goal-related activity in hippocampal
      place cells. J Neurosci 2007;27:472-82.] that neurones in the dorsal hippocampus
      exhibit anticipatory firing prior to the release of a food pellet on an operant
      task. Here we look for similar activity in the mPFC on the same task and test
      whether this activity is dependent on the hippocampus. Rats were trained to
      navigate to a goal zone, wait for the release of a food pellet and then forage
      for the pellet while unit activity was recorded in the prelimbic and infralimbic
      areas of the mPFC. Two 16 min sessions were conducted per day, one session with
      the goal delimited by a cue disc, the second without the cue. In controls, a
      large proportion of mPFC neurones exhibited activity similar to that seen in the
      hippocampus while the animal was stationary at the goal. Over half exhibited the
      same activity regardless of goal location. Anticipatory activity was largely
      abolished in animals with bilateral lesions of the ventral and intermediate
      hippocampus, both in cued and uncued sessions. Even though lesioned animals
      continued to perform the task, they tended to leave the goal zone prematurely. We
      suggest that the anticipatory activity in the mPFC is dependent on similar
      activity in the hippocampus and that both structures have a role in either
      impulse control or reward expectation.

PMID- 19103228
TI  - Candesartan improves memory decline in mice: involvement of AT1 receptors in
      memory deficit induced by intracerebral streptozotocin.
AB  - The Renin-angiotensin system, besides blood pressure regulation, affects learning
      and memory as evidenced by improvement of cognition in hypertensive patients
      being treated with AT1 receptor blockers like candesartan. The present study
      examined the influence of candesartan on memory impairment induced by
      intracerebral streptozotocin (IC STZ 0.5 mg/kg) in mice. Candesartan (0.05 mg/kg
      and 0.1 mg/kg, i.p.) was given for 14 days following IC STZ administration. The
      dose of 0.1 mg/kg significantly improved latency period in passive avoidance
      test. Further, treatment with 0.1 mg/kg candesartan for 14 days significantly
      improved spatial memory in mice in water maze test also. In another group, after
      memory impairment in mice following IC STZ administration, memory improving
      effect of a 7 days treatment with 0.1 mg/kg candesartan lasted only for 3
      subsequent days in water maze task. IC STZ increased oxidative stress but
      pretreatment with 0.1 mg/kg candesartan decreased oxidative stress as indicated
      by a decrease in MDA and increase in GSH. Further, candesartan decreased free
      radicals as evidenced by flow cytometry. IC STZ affected cholinergic system also
      by increasing acetylcholine esterase activity that was restored by pretreatment
      with 0.1 mg/kg candesartan. Locomotor activity and serum glucose level remained
      unaffected by candesartan treatment. These results suggest that AT1 receptors
      play a facilitatory role in STZ induced memory deficit and corroborate number of
      human studies that AT1 receptor blockers can be used therapeutically against
      cognitive decline in hypertensive patients.

PMID- 19103229
TI  - Effects of environmental novelty on fear-related behavior and stress responses of
      rats to emotionally relevant odors.
AB  - Although various emotional behaviors and activation of the hypothalamic-pituitary
      adrenal (HPA) axis of rats are induced by the exposure of 2,5-dihydro-2,4,5
      trimethylthiazoline: TMT, a component of fox odor, these odor-induced responses
      are influenced by the external environment. Our previous study demonstrated that
      exposure to green odor, a mixture of cis-3-hexenol and trans-2-hexenal,
      attenuated stress-induced elevation of the plasma ACTH level in rats. The present
      study investigated the effect of TMT or green odor on emotional behavior and the
      HPA axis stress response with or without the influence of environmental novelty.
      We exposed rats to TMT or green odor in "familiar" or "unfamiliar" environments
      and compared the various responses, including fear-related behaviors, non
      defensive behaviors and plasma ACTH concentrations. TMT induced enhanced freezing
      behavior, reduced exploration behavior and elevations in plasma ACTH
      concentrations in two environmental conditions. Comparing TMT-induced responses
      in an unfamiliar environment with the familiar environment showed that
      environmental novelty enhanced TMT-induced fear-related behaviors and elevations
      of plasma ACTH concentrations. These results revealed that TMT causes fear and
      stress responses in both familiar and unfamiliar environments, although the
      novelty of an unfamiliar environment enhances these TMT-induced responses. On the
      other hand, green odor did not induce any responses in either environment. These
      findings indicate that odor-induced responses are influenced by the surrounding
      environment.

PMID- 19103230
TI  - Short-term full kindling of the amygdala dissociates natural and periaqueductal
      gray-evoked flight behaviors of the rat.
AB  - Panic attacks present a high comorbidity with agoraphobia, separation anxiety and
      generalized anxiety disorder. Nevertheless, while panic attacks have been
      frequently equated to fear, the relationship of panic disorder with specific
      phobias remains uncertain. The combination of experimental models of panic and
      phobias could but afford valuable information about both the comorbidity and
      causation of these disorders. As it regards, while the defensive behaviors
      produced by stimulation of dorsal periaqueductal gray matter (DPAG) resemble a
      panic attack, resistance to capture (RC) behaviors that ensue the kindling of the
      amygdala (AMY) are reminiscent of a phobic reaction. Therefore, this study
      examined the thresholds of DPAG-evoked panic-like behaviors in rats showing RC
      behaviors. Rats bearing electrodes in the DPAG and right AMY were subjected to
      either the full- (Kin-F) or sham- (Kin-S) kindling of AMY. RC behaviors were
      evaluated throughout both kindling procedures. Thresholds of DPAG-evoked
      defensive behaviors were recorded before and after the kindling. Moreover,
      performances of Kin-F and Kin-S rats in the elevated plus-maze were compared to
      those of intact controls. Data showed that Kin-F and Kin-S rats perform similarly
      in the elevated plus-maze, thereby making AMY-kindled rats unlikely as a model of
      generalized anxiety disorder. On the other hand, whereas the RC is characterized
      by a marked facilitation of natural freezing and flight behaviors, DPAG-evoked
      freezing (immobility and exophthalmus) and flight (galloping) behaviors were
      unexpectedly attenuated. Data suggest that RC is mediated by circuits distinct
      from those of DPAG-evoked defensive behaviors. Consequently, panic and phobic
      attacks may be mediated by different mechanisms as well.

PMID- 19103231
TI  - Acetate:succinate CoA-transferase in the anaerobic mitochondria of Fasciola
      hepatica.
AB  - Fasciola hepatica contains anaerobically functioning mitochondria that produce
      acetate and propionate, the main endproducts excreted by this parasite. The final
      reactions in the pathways leading to these endproducts are performed by
      acetate:succinate CoA-transferase (ASCT) and propionate:succinate CoA-transferase
      (PSCT), respectively. The enzymes catalysing these essential reactions in
      anaerobic mitochondria are still not characterized, nor are the corresponding
      genes identified. Here we describe the identification of the gene that codes for
      the F. hepatica ASCT. The F. hepatica gene was heterologously expressed and
      studies on the corresponding enzyme activity showed that the enzyme is indeed a
      transferase and uses a ping-pong bi-bi reaction mechanism, like most other known
      CoA-transferases. This F. hepatica CoA-transferase was shown to be a true
      transferase and not a hydrolase, as it needs an acceptor for optimal activity.
      Our studies demonstrated that the F. hepatica ASCT can use other CoA-acceptors
      than succinate, such as propionate, acetate and butyrate, and is in fact a short
      chain acyl-CoA-transferase. We further showed that this F. hepatica CoA
      transferase can also catalyze the PSCT reaction, which is responsible for the
      production of propionate. Analysis of the amino acid sequence of F. hepatica
      clearly indicated the presence of a mitochondrial targeting sequence, and in CHO
      cells the enzyme is indeed present in the mitochondrial fraction. F. hepatica
      ASCT is the first ASCT identified in anaerobic mitochondria. It is homologous to
      the hydrogenosomal ASCT we earlier identified in Trichomonas vaginalis, but not
      to the ASCT present in the aerobic mitochondria of Trypanosoma brucei.

PMID- 19103232
TI  - Plasmodium falciparum secretory pathway: characterization of PfStx1, a plasma
      membrane Qa-SNARE.
AB  - SNAREs (soluble N-ethylmaleimide-sensitive factor attachment protein receptors)
      play a central role in regulating and facilitating vesicular traffic in
      eukaryotic cells. While SNAREs have been well characterized in other eukaryotes,
      little is known about their role in the unique protein trafficking pathways in
      Plasmodium falciparum. We have identified seven Qa-SNAREs in the P. falciparum
      genome and confirmed the gene structure of all seven, which in one case differs
      from the predicted structure in the database. Based on comprehensive sequence
      alignments we made predictions for the intracellular locations of all seven P.
      falciparum Qa-SNAREs, and confirmed the predicted location for one Qa-SNARE,
      PfStx1, which is most closely related to other eukaryotic plasma membrane Qa
      SNAREs such as syntaxin 1. This is the first identified trafficking component
      localized proximal to the P. falciparum plasma membrane.

PMID- 19103233
TI  - Molecular mechanisms of TRP regulation in tumor growth and metastasis.
AB  - Transient Receptor Potential (TRP) channels modulate intracellular Ca2+
      concentrations, consequently affecting both cell death and proliferation. It is
      not, therefore, surprising that the membrane expression of some TRP channels is
      altered during tumor growth and metastasis. These variations in channel abundance
      are due to TRP regulation on the transcriptional, translational, and targeting
      levels. This article mainly reviews the transcriptional mechanisms modulating TRP
      expression during tumorigenesis, involving hormones, growth factors, and
      alternative splicing.

PMID- 19103234
TI  - Selective detection of live bacteria combining propidium monoazide sample
      treatment with microarray technology.
AB  - The use of DNA-based molecular detection tools for bacterial diagnostics is
      hampered by the inability to distinguish signals originating from live and dead
      cells. The detection of live cells is typically most relevant in molecular
      diagnostics. DNA-intercalating dyes like ethidium monoazide and propidium
      monoazide (PMA) offer a possibility to selectively remove cells with compromised
      cell membranes from the analysis. Once these dyes enter a cell, they bind to DNA
      and can be covalently crosslinked to it by light exposure. PCR amplification of
      such modified DNA is strongly inhibited. In this study we evaluated the
      suitability of propidium monoazide treatment to exclude isopropanol-killed cells
      from detection in defined mixtures using diagnostic microarray technology. The
      organisms comprised Pseudomonas aeruginosa, Listeria monocytogenes, Salmonella
      typhimurium, Serratia marcescens, and Escherichia coli O157:H7. PCR products
      obtained from amplification of chaperonin 60 genes (cpn60; coding for GroEL) were
      hybridized to a custom-designed microarray containing strain-specific cpn60-based
      35-mer oligonucleotide probes. Results were compared with data from quantitative
      PCR, which confirmed that PMA could successfully inhibit amplification of DNA
      from killed cells in the mixtures. Although microarray data based on analysis of
      end-point PCR amplicons is not quantitative, results showed a significant signal
      reduction when targeting killed cells and consistently agreed with qPCR results.
      Treatment of samples with PMA in combination with diagnostic microarray detection
      can therefore be considered beneficial when analyzing mixtures of intact and
      membrane-compromised cells. Minimization of detection signals deriving from dead
      cells will render data more relevant in studies including pathogen risk
      assessment.

PMID- 19103236
TI  - Spatial-temporal distribution of nitric oxide involved in regulation of
      phenylalanine ammonialyase activation and Taxol production in immobilized Taxus
      cuspidata cells.
AB  - The generation of nitric oxide (NO) in Taxus cuspidata in immobilized support
      matrices and the potential role of NO as signal molecular in regulation of Taxol
      production were investigated. It was found that the immobilization induced a
      spatial and temporal-dependent NO burst in immobilized supported matrices. NO
      level reached the maximum in the central zone of immobilized supported matrices
      on day 20, which was more than twice compared with that in suspended cells.
      Further investigations showed that the phenylalanine ammonialyase (PAL) activity
      and Taxol production of the 20-day-old immobilized T. cuspidata cells increased
      by onefold and 11% after 4h treatment with 20 microM NO donor (sodium
      nitroprusside), respectively. NO inhibitor N(omega)-nitro-L-arginine and NO
      scavenger 2-phenyl-4,4,5,5-tetramethyl-imidazoline-1-oxyl-3-oxyde partially
      blocked PAL activity and Taxol accumulation in immobilized cells. These results
      suggest that NO plays a signal role in regulation of PAL activity and Taxol
      production in immobilized T. cuspidata cells.

PMID- 19103235
TI  - A portal for rhizobial genomes: RhizoGATE integrates a Sinorhizobium meliloti
      genome annotation update with postgenome data.
AB  - Sinorhizobium meliloti is a symbiotic soil bacterium of the alphaproteobacterial
      subdivision. Like other rhizobia, S. meliloti induces nitrogen-fixing root
      nodules on leguminous plants. This is an ecologically and economically important
      interaction, because plants engaged in symbiosis with rhizobia can grow without
      exogenous nitrogen fertilizers. The S. meliloti-Medicago truncatula (barrel
      medic) association is an important symbiosis model. The S. meliloti genome was
      published in 2001, and the M. truncatula genome currently is being sequenced.
      Many new resources and data have been made available since the original S.
      meliloti genome annotation and an update was needed. In June 2008, we submitted
      our annotation update to the EMBL and NCBI databases. Here we describe this new
      annotation and a new web-based portal RhizoGATE. About 1000 annotation updates
      were made; these included assigning functions to 313 putative proteins, assigning
      EC numbers to 431 proteins, and identifying 86 new putative genes. RhizoGATE
      incorporates the new annotion with the S. meliloti GenDB project, a platform that
      allows annotation updates in real time. Locations of transposon insertions,
      plasmid integrations, and array probe sequences are available in the GenDB
      project. RhizoGATE employs the EMMA platform for management and analysis of
      transcriptome data and the IGetDB data warehouse to integrate a variety of
      heterogeneous external data sources.

PMID- 19103237
TI  - In vitro replicative properties of replicons constructed using sequence variants
      of the hepatitis C virus strain AD78 that caused a single-source outbreak of
      hepatitis C.
AB  - For many aspects of HCV research it would be very useful to have a set of
      replicons in which different genome regions are swapped by corresponding
      fragments from isolates of the same viral strain that might demonstrate different
      biological characteristics or bear evolving antigenic determinants. The isolates
      of the same HCV strain that are necessary for generation of such hybrid replicons
      might be obtained from a single-source outbreak of HCV infection. One such
      outbreak caused by the HCV AD78 strain, occurred in Germany due to infection of
      women by contaminated anti-D globulin. Using a sequential substitution of
      different segments of the Con1 replicon with the corresponding fragments from the
      AD78 strain of HCV, a set of chimeric Con1/AD78 subgenomic and full-length, AD78
      based genomic replicons were generated. These replicons might be used as a new
      experimental tool for different aspects of HCV research, including studies of the
      nature of isolate-specific differences in interactions of the replicon with the
      host cell and analysis of the mechanisms of HCV resistance to antivirals. The
      newly generated full-length replicon can also be used for preparation of AD78
      specific target cell lines, which may be invaluable for the analysis of the
      evolution of HCV cellular immune responses in the cohort of patients infected
      with the HCV AD78 strain.

PMID- 19103238
TI  - Dendrimer polymeric micelles for enhanced photodynamic cancer treatment.

PMID- 19103239
TI  - Amphetamine derivatives and obesity.
AB  - This study aims to investigate the anamnestic, psychopatological and clinical
      features of overweight/obese subjects with and without an history of amphetamine
      derivatives consumption. This survey was conducted on a consecutive series of 451
      overweight/obese subjects referring to the Clinics for Obesity of the University
      of Florence. Subjects with and without previous amphetamines derivatives
      consumptions were compared in terms of psychopathological and clinical features
      by means of the Structured Clinical Interview for DSM-IV, the Eating Disorder
      Examination questionnaire (EDE-Q), the Binge Eating Scale (BES), the Beck
      Depression Inventory (BDI), and the Spielberg's State-Trait Anxiety Inventory
      (STAI). Among the 451 participants, 136 patients (30.1%) reported a previous use
      of amphetamine derivatives drugs. Amphetamine users reported a high rate of
      childhood overweight, and showed higher BMI, EDE-Q Total score, Weight Concern,
      Shape Concern subscales and BES scores than amphetamine non-users, whereas the
      two groups of patients did not differ in terms of BDI and STAI scores.
      Amphetamine derivatives are widely used by obese patients seeking weight loss
      treatment. The amphetamine derivatives consumption is associated with higher
      levels of eating psychopathology and a more severe overweight.

PMID- 19103240
TI  - Purification, partial characterization and molecular cloning of the novel
      antiviral protein RC28.
AB  - An antiviral protein, RC28, with anti-herpesvirus activity was purified from a
      PBS extract of Rozites caperata (Cortinarious caperata) by acetone precipitation
      followed by gel filtration and ion exchange chromatography. The molecular weight
      of this protein was 28.251kDa as measured by MALDI-TOF mass spectrography. Our
      preparation of RC28 inhibited HSV-1 replication in vitro with an IC(50) value of
      0.078mg/ml and a therapeutic index >32. The first 30 amino acid residues of RC28
      were sequenced by Edman degradation to be MLTYRGKLNWYNYAVNEGFTLILPGXELKV. Based
      on that sequence, two degenerate primers were designed, the RC28 cDNA fragment
      was cloned by 3'-RACE, and the rest of the amino acid sequence was inferred from
      the cDNA sequence. The full-length peptide chain of RC28 has 235 amino acid
      residues, and was modified after its translation naturally. A search of the
      literature showed that this sequence has not been reported before and does not
      belong to any known protein family. A preliminary expression system was also
      constructed by inserting the cDNA into the PQE-30 vector, and transformed into
      Escherichia coli.

PMID- 19103241
TI  - Molecular cloning and functional identification of a new K(+) channel blocker,
      LmKTx10, from the scorpion Lychas mucronatus.
AB  - Scorpions have a venom gland which is an important determinant in contributing to
      their successful survival for more than 400 million years. Their venoms contain a
      diversity of neurotoxins, which represent a tremendous hitherto partially
      unexplored resource not only for understanding ion channels but also for use in
      drug design and development. In this investigation, LmKTx10, a new toxin gene was
      identified from the venom of the scorpion Lychas mucronatus by constructing cDNA
      library method, and its product was expressed and characterized physiologically.
      The mature peptide has 38 residues including six conserved cysteines. The
      electrophysiological experiments further indicated that the recombinant LmKTx10
      peptide has an interesting pharmacological profile: it blocks Kv1.3 channel with
      IC(50)=28nM which is moderate Kv1.3 channel blocking activity compared to the
      other a-KTxs toxins, and exhibits good selectivity on Kv1.3 over Kv1.1 and Kv1.2,
      about 60 folds and 450 folds, respectively. These data not only enrich the family
      of K(+) channel toxins from scorpion venoms but also present a potential drug
      template for selectively targeting the Kv1.3 channel.

PMID- 19103242
TI  - Solution conformations of an insect neuropeptide: crustacean cardioactive peptide
      (CCAP).
AB  - The solution structure of crustacean cardioactive peptide (CCAP), a cyclic
      amidated nonapeptide neurohormone, was studied using molecular dynamics
      techniques, with constraints derived from NMR studies in water and
      water/dodecylphosphocholine micellar medium. This peptide, found in various
      invertebrates, has the primary sequence Pro(1) Phe(2) Cys(3) Asn(4) Ala(5) Phe(6)
      Thr(7) Gly(8) Cys(9) NH(2), with an intramolecular disulfide bridge between the
      two cysteine residues. In aqueous solution the peptide was found to have a
      type(IV) beta-turn between residues 5-8. In a water/decane biphasic medium a
      type(IV) beta-turn between residues 3 and 6 and two classic gamma-turns between
      residues 4-6 and 7-9, were found. Analysis of the (1)H and (13)C NMR chemical
      shifts data showed that the model free S(2) order parameter of the residues
      varied between 0.65 and 0.9. The molecular dynamic root mean square fluctuations
      of structural ensembles of the backbone varied between 0.5 and 2.2 with the
      central residues showing the least fluctuations.

PMID- 19103243
TI  - Transient global ischemia in rat brain promotes different NMDA receptor
      regulation depending on the brain structure studied.
AB  - The mRNA expression of the major subunits of N-methyl-d-aspartate receptors (NR1,
      NR2A and NR2B) following ischemia-reperfusion was studied in structures with
      different vulnerabilities to ischemic insult in the rat brain. The study was
      performed using quantitative real-time PCR on samples from 3-month-old male
      Sprague-Dawley rats after global transient forebrain ischemia followed by 48h of
      reperfusion. Expression of NMDA receptor subunits mRNAs decreased significantly
      in all structures studied in the injured animals as compared to the sham-operated
      ones. The hippocampal subfields (CA1, CA3 and dentate gyrus) as well as the
      caudate-putamen, both reported to be highly ischemic-vulnerable structures,
      showed outstandingly lower mRNA levels of NMDA receptor subunits than the
      cerebral cortex, which is considered a more ischemic-resistant structure. The
      ratios of the mRNA levels of the different subunits were analyzed as a measure of
      the NMDA receptor expression pattern for each structure studied. Hippocampal
      areas showed changes in NMDA receptor expression after the insult, with
      significant decreases in the NR2A with respect to the NR1 and NR2B subunits.
      Thus, the NR1:NR2A:NR2B (1:1:2) ratios observed in the sham-operated animals
      became (2:1:4) in insulted animals. This modified expression pattern was similar
      in CA1, CA3 and the dentate gyrus, in spite of the different vulnerabilities
      reported for these hippocampal areas. In contrast, no significant differences in
      the expression pattern were observed in the caudate-putamen or cerebral cortex on
      comparing the sham-operated animals with the ischemia-reperfused rats. Our
      results support the notion that the regulation of NMDA receptor gene expression
      is dependent on the brain structure rather than on the higher or lower
      vulnerability of the area studied.

PMID- 19103245
TI  - An overview of the National Network for Immunization Information's website.
AB  - The National Network for Immunization Information (NNii) hosts a website to
      provide scientifically valid information about immunization issues. Overall,
      NNii's website is balanced and informative, providing reviews for parents,
      patients, and clinicians. Having a website from a non-profit without financial
      conflicts of interest is key in the ongoing debates about vaccine safety.

PMID- 19103244
TI  - Development of effective vaccines for old mice in a tumor model.
AB  - Vaccines are often inefficient in old people and old mice. Few studies have
      focused on testing vaccines in old populations. Here we used DNA tumor antigen
      vaccines against melanoma and showed that old mice were not protected. Vaccines
      incorporating fusions of the tumor antigen with microbial adjuvant proteins OmpA
      (E. Coli) or Vp22 (Herpes simplex virus-1) dramatically improved protection of
      old mice. The mechanisms by which these adjuvant proteins act are distinct. TLR2
      was not required for either OmpA or Vp22. Antigen processing and presentation
      were not boosted by these fusion constructs. However, fusion constructs with Vp22
      gave a strong CD4 response to B16 melanoma and the OmpA response is MHC-II
      dependent. Both adjuvant fusion constructs stimulated CD4 and CD8 responses
      otherwise diminished in old mice.

PMID- 19103246
TI  - Priming with a DNA vaccine delivered by attenuated Salmonella typhimurium and
      boosting with a killed vaccine confers protection of chickens against infection
      with the H9 subtype of avian influenza virus.
AB  - Control of the circulation of H9 low-pathogenic avian influenza virus (LPAIV) is
      a major concern for both animal and public health. To improve vaccine efficacy
      against H9 LPAIV, we have utilized a novel prime-boost vaccination strategy.
      Specific-pathogen free (SPF) chickens were first orally immunized with a
      hemagglutinin (HA) DNA vaccine delivered by attenuated Salmonella typhimurium,
      followed by boosting with a killed avian influenza (AI) vaccine. Chickens in this
      combined vaccination group were completely protected against both oropharyngeal
      and cloacal virus shedding after intranasal challenge with H9N2 AIV, while
      viruses were detected from these sites in other vaccination groups. Prior to
      challenge, chickens in the prime-boost group also had higher (P<0.05) serum
      hemagglutination inhibition (HI) titers and intestinal mucosal IgA ELISA titers
      against AIV, and higher lymphoproliferation stimulation indices than those from
      other groups. Thus, we have demonstrated the efficacy of a novel prime-boost
      vaccination strategy against H9N2 avian influenza virus, which could be also
      applied for the development of vaccines against other mucosally infectious
      pathogens.

PMID- 19103247
TI  - Letter to the editor in response to Forristal et al.: Improving the quality of
      risk assessments in Canada using a principle-based approach, regulatory
      toxicology and pharmacology 50 (2008) 336-344.

PMID- 19103248
TI  - Lack of chronic toxicity or carcinogenicity of dietary N-acetylglucosamine in
      F344 rats.
AB  - Chronic toxicity and carcinogenicity of N-acetylglucosamine (GlcNAc) were
      examined in male and female F344 rats. GlcNAc was given in the diet at levels of
      0%, 1.25%, 2.5% or 5% to groups of 10 rats of each sex for 52 weeks in the
      chronic toxicity study and 0%, 2.5% or 5% to groups of 50 rats of each sex for
      104 weeks in the carcinogenicity study. GlcNAc exerted no toxic effects with
      regard to clinical signs, mortality, hematology, serum biochemistry and
      histopathological assessment. Slight suppression of body weight gain was observed
      at more than 2.5%, but this appeared to be due to slight reduction of caloric
      intake with the high concentration of test compound, rather than any toxicity.
      Thus, it was concluded that GlcNAc has neither toxic nor carcinogenic effects in
      F344 rats, the no observed adverse effect levels (NOAEL) estimated from the
      chronic toxicity study being 5% in both sexes, equivalent to 2323 and 2545
      mg/kg/day in males and females, respectively.

PMID- 19103249
TI  - Brain potentials during affective picture processing in children.
AB  - In adults, emotional (e.g., both unpleasant and pleasant) compared to neutral
      pictures elicit an increase in the early posterior negativity (EPN) and the late
      positive potential (LPP); modulation of these ERP components are thought to
      reflect the facilitated processing of, and increased attention to, motivationally
      salient stimuli. To determine whether the EPN and LPP are sensitive to emotional
      content in children, high-density EEG was recorded from 18 children who were 5-8
      years of age (mean age=77 months, SD=11 months) while they viewed developmentally
      appropriate pictures selected from the International Affective Picture System.
      Self-reported ratings of valence and arousal were also obtained. An EPN was not
      evident following emotional compared to neutral pictures; however, a positivity
      maximal at occipital-parietal recording sites was increased from 500 to 1000 ms
      following pleasant pictures and from 500 to 1500 ms following unpleasant
      pictures. Comparisons between the EPN and LPP observed in children and adults,
      and implications for developmental studies of emotion, are discussed.

PMID- 19103251
TI  - Smoking and sVEGFR-1: circulating maternal concentrations and placental
      expression.
AB  - Smoking reduces the expression of VEGFR-1 in non-pregnant women. In pregnant
      women it reduces the risk of pre-eclampsia, which in turn is associated with
      increased placental expression of VEGFR-1 and increased maternal circulating
      soluble VEGFR-1 (sVEGFR-1). We therefore hypothesized that smoking might affect
      VEGFR-1 expression in pregnant women. In maternal plasma sVEGFR-1 concentrations
      during the third trimester in both smoking (median 1088, range 834-1362ng/L,
      n=20) and non-smoking (728, 719-1336ng/L, n=19) women were higher than during the
      second trimester (smokers 374, 291-683ng/L, n=6, p>0.05; non-smokers 375, 290
      667ng/L, n=22, p<0.001). No difference was observed between smokers and non
      smokers. Secretion of sVEGFR-1 into the culture medium, as well as the pattern
      and intensity of immunostaining in first trimester placenta were similar in
      tissue from smoking (n=22) and non-smoking (n=20) women. Thus, contrary to our
      hypothesis, smoking does not affect circulating maternal sVEGFR-1 concentrations
      or placental secretion of sVEGFR-1 or expression of VEGFR-1 in vitro.

PMID- 19103252
TI  - Glatiramer acetate positively influences spinal motoneuron survival and synaptic
      plasticity after ventral root avulsion.
AB  - Avulsion of ventral roots induces degeneration of most axotomized motoneurons. At
      present there are no effective strategies to prevent such neuronal loss and to
      preserve the affected spinal circuits. Interestingly, changes in the spinal cord
      network also occur during the course of the experimental model of multiple
      sclerosis (experimental autoimmune encephalomyelitis-EAE). Glatiramer acetate
      (GA) significantly reduces the seriousness of the symptoms during the
      exacerbation of EAE. However, little is known about its effects on motoneurons.
      In the present study, we investigated whether GA has an influence on synapse
      plasticity and glial reaction after ventral root avulsion (VRA). Lewis rats were
      subjected to the avulsion of lumbar ventral roots and treated with GA. The
      animals were sacrificed after 14 days of treatment and the spinal cords processed
      for immunohistochemistry. A correlation between the synaptic changes and glial
      activation was obtained by performing immunolabeling against synaptophysin, GFAP
      and Iba-1. GA treatment preserved synaptophysin labeling, and significantly
      reduced the glial reaction in the area surrounding the axotomized motoneurons.
      After ventral root avulsion, GA treatment was also neuroprotective. The present
      results indicate that the immunomodulator GA has an influence on the stability of
      nerve terminals in the spinal cord, which may in turn contribute to future
      treatment strategies after proximal lesions to spinal motoneurons.

PMID- 19103253
TI  - Autophagy is involved in the ischemic preconditioning.
AB  - Autophagy is a key pathway for the clearance of damaged organelles. Ischemic
      preconditioning (IPC) and autophagy are enhanced by mild hypoxic insults, but the
      association between autophagy and IPC remains unclear. We investigated the
      existence and role of autophagy in IPC. In an in vitro PC12 cell model, IPC
      increased generation and degradation of autophagosomes, as revealed by increased
      LC3-II bands, cathepsin D positive cells, lysosomal activity and autophagic
      vacuoles on electron microscopy. Autophagic activity was blocked using 3
      methyladenine during IPC, and cell viabilities were measured using FASC and WST-1
      assays. Inhibition of autophagy, especially during reperfusion or lethal oxygen
      glucose deprivation periods ameliorated the neuroprotective effects of IPC.
      Moreover, inhibiting autophagy also attenuated Hsp70 upregulation induced by IPC.
      These findings imply that autophagy participates in IPC-induced neuroprotection,
      and that autophagy might provide a means of neuroprotection against cerebral
      ischemia.

PMID- 19103250
TI  - Insulin/IGF-1 and ROS signaling pathway cross-talk in aging and longevity
      determination.
AB  - Regulation of hormonal, insulin/IGF-1 (Ins/IGF-1) signaling activities, and
      pathways of the intrinsic generation of reactive oxygen species (ROS) play a role
      in aging and longevity determination. In this review we discuss the cross-talk
      between these pathways as mechanisms of signaling that may be important factors
      in the regulation of aging and longevity. The balance of physiological processes
      controlling the rate of aging and longevity in several mouse mutants suggests the
      involvement of cross-talk mechanisms of regulation of the insulin/IGF1 signaling
      pathway vs. the ROS signaling pathways. In mice, modulation of the Ins/IGF-1
      signaling pathways resulting from the Prop1(df), Pit1(dw) and Igf1 receptor
      mutations exemplify the hormonal pathways associated with aging and longevity
      determination. These pathways are also targets of the ROS-mediated redox
      pathways. Similarly, the Klotho and p66(Shc) mutants link regulation of ROS
      signaling pathways to aging and longevity determination. Both of these models
      also display altered insulin signaling activity, a characteristic associated with
      longevity. The Ins/IGF-1 signaling pathway is of particular interest because of
      its decreased activity due to genetic manipulation vs. its responsiveness to ROS
      levels.

PMID- 19103254
TI  - Differential activation of face memory encoding tasks in alcohol-dependent
      patients compared to healthy subjects: an fMRI study.
AB  - It has been hypothesized that the right hemisphere of the brain is more sensitive
      to alcohol-related damage than the left hemisphere. The present study tested this
      hypothesis, using functional MRI to determine whether the pattern for right
      hemispheric activity is different for alcohol-dependent patients, compared to
      normal healthy individuals. Two different types of memory encoding tasks were
      performed separately: word and face encoding for both alcohol-dependent patients
      and normal healthy volunteers. The data for the normal volunteers indicate that
      the left prefrontal region is more active during word encoding, whereas the right
      parahippocampal region is more active during face encoding. The results for the
      patient data, however, demonstrated left lateralization in the prefrontal area
      during word encoding, while right lateralization in the parahippocampal region
      during face encoding was not observed. Therefore, alcoholism appears to have no
      influence on left hemispheric activity, since the activation pattern was similar
      to that observed for normal healthy persons. However, the absence of right
      hemispheric lateralization in alcohol-dependent patients is consistent with the
      hypothesis that the right hemisphere is more vulnerable to alcohol-related damage
      than the left hemisphere.

PMID- 19103255
TI  - Vomeronasal neurons promote synaptic formation on dendritic spines but not
      dendritic shafts in primary culture of accessory olfactory bulb neurons.
AB  - To investigate the morphological changes of accessory olfactory bulb (AOB)
      neurons arising from pheromonal signals, a coculture system of AOB neurons and
      vomeronasal (VN) neurons had been established. Our previous study indicates that
      under coculture condition, the density of dendritic spines of an AOB neuron is
      less and the individual spine-head volume is larger than those under monoculture
      condition. In this study, to determine whether these differences in the dendrites
      of AOB neurons reflect the differences in synapse formation and synaptic
      properties, we observed these cultured cells by electron microscopy. Various
      synapses were observed under each culture condition. Synapses were classified on
      the basis of their postsynaptic structure and the size of postsynaptic density
      (PSD) was measured. Under the coculture condition with VN neurons, synapses on
      dendritic spines, which formed between AOB neurons, were observed frequently. In
      contrast, many synapses were formed on dendritic shafts under monoculture
      condition. The PSD of asymmetrical synapses on the spines under coculture
      condition was larger than that under monoculture condition. Moreover, some
      dendrodendritic reciprocal synapses were found only in coculture. We confirmed
      synapse formation between VN axons and AOB dendrites by immunohistochemical
      electron microscopy; thus, the characteristics of synapses between AOB neurons
      are considered to be modified by the synaptic contacts with VN axons.

PMID- 19103256
TI  - TLS interaction with NMDA R1 splice variant in retinal ganglion cell line RGC-5.
AB  - Translocated in liposarcoma (TLS or FUS) is a multifunctional protein component
      of the heterogenous ribonuclear complex involved in the splicing of pre-mRNA and
      the export of fully processed mRNA from the nucleus to the cytoplasm. As we
      determined that TLS was substantially expressed in the adult retina, we
      investigated the functions of TLS in a rat retinal ganglion cell (RGC) line RGC
      5. TLS was found to be associated with N-methyl-d-aspartate (NMDA) receptor 1
      (NR1) and myosinVa (MyoVa) in a calcium-dependent manner. We demonstrated that
      TLS-associated NR1 could be one of the NR1 alternative splice variants, NR1-4,
      which was predominantly expressed in RGC-5. The degree of colocalization between
      TLS and NR1 was significantly decreased by depolarization of RGC-5 cells,
      indicating that the depolarization-induced Ca(2+)-influx triggered a
      redistribution of NR1 from the TLS-protein complex. These results suggested that
      TLS might be involved in a calcium-dependent trafficking of specific NR1 splice
      variants in RGCs.

PMID- 19103257
TI  - Cyclin C and cyclin dependent kinases 1, 2 and 3 in thrombin-induced neuronal
      cell cycle progression and apoptosis.
AB  - The extent to which neurons proceed into the cell cycle and the mechanisms
      whereby cell cycle re-entry leads to apoptosis vary in response to agonists. We
      previously showed upregulation of early G1 regulators in thrombin-treated neurons
      yet neurons did not proceed to S phase but to apoptosis. The objective of this
      study is to explore mechanisms which might prevent S phase entry and promote
      apoptosis in thrombin-treated neurons. Cultured rat brain neurons are exposed to
      thrombin (200nM) for 30min to 4.5h and the expression of cyclin C, cyclin
      dependent kinases (cdk1, cdk2, cdk3, cdk8) and the cell cycle inhibitor p27
      assessed. Our data show a simultaneous decrease of both cyclin C and cdk3
      proteins soon after thrombin treatment. The decrease in cyclin C also correlates
      with decreases in cdk1 and cdk2, at both mRNA and protein levels. There is no
      change in expression of cdk8 or the cell cycle inhibitor p27 in response to
      thrombin treatment. These results suggest that decreases in G1-S regulators
      cyclin C and cdks 3, cdk2 and cdk1 in response to thrombin could make conditions
      unfavorable for S phase entry and favor neuronal apoptosis.

PMID- 19103258
TI  - Inhibition of swallowing reflex following phosphorylation of extracellular signal
      regulated kinase in nucleus tractus solitarii neurons in rats with masseter
      muscle nociception.
AB  - Pain is associated with swallowing abnormalities in dysphagic patients.
      Understanding neuronal mechanisms underlying the swallowing abnormalities
      associated with orofacial abnormal pain is crucial for developing new methods to
      treat dysphagic patients. However, how the orofacial abnormal pain is involved in
      the swallowing abnormalities is not known. In order to evaluate neuronal
      mechanisms of modulation of the swallows by masticatory muscle pain, here we
      first induced swallows by topical administration of distilled water to the
      pharyngolaryngeal region. The swallowing reflex was significantly inhibited after
      capsaicin (10, 30mM) injection into the masseter muscle compared to vehicle
      injection. Moreover the number of phosphorylated extracellular signal-regulated
      kinase-like immunoreactive (pERK-LI) neurons in the nucleus tractus solitarii
      (NTS) was significantly increased in the rats with capsaicin injection into the
      masseter muscle compared to that with vehicle injection. Rostro-caudal
      distribution of pERK-LI neurons in the NTS was peaked at the obex level. The
      capsaicin-induced inhibitory effect on swallowing reflex was reversed after
      intrathecal administration of mitogen-activated protein kinase (MAPK) kinase
      (MEK) inhibitor, PD98059. The present findings suggest that phosphorylation of
      ERK in NTS neurons may be involved in capsaicin-induced inhibition of swallowing
      reflex.

PMID- 19103259
TI  - Differentiation/maturation of neuropeptide Y neurons in the corpus callosum is
      promoted by brain-derived neurotrophic factor in mouse brain slice cultures.
AB  - Neuropeptide Y (NPY) is widely distributed throughout both the central and
      peripheral nervous systems in mammals, and plays a role in various functions such
      as neural modifications affecting feeding, cardiovascular dynamics, or neural
      diseases. Many NPY neurons exist not only in gray matter in the central nervous
      system or ganglia in the peripheral system, but also in white matter such as the
      corpus callosum (cc) especially during development. The functions and regulation
      of callosal NPY neurons are not well understood, though NPY neurons in the
      cerebral cortex or hypothalamus are known to be regulated by neurotrophic factors
      such as brain-derived neurotrophic factor (BDNF). We examined the effect of BDNF
      on NPY neurons in the cc using organotypic slice cultures to clarify the
      regulation of callosal NPY neurons. A 3-week administration of BDNF significantly
      increased the number of NPY-immunopositive neuronal cell bodies and fibers in the
      cc rather than in the cerebral cortex as assessed with immunohistochemistry.
      Electron microscopy demonstrated that the NPY immunoreactivity mainly occurred in
      the regions associated with accumulating synaptic or cored vesicles. NPY-positive
      fibers had some contacts with several other neuronal fibers and glial processes.
      BDNF affected these fine structures of NPY neuronal fibers in the cc. These
      results suggest that BDNF takes part in the development, maturation, and
      maintenance of NPY neurons in the cc.

PMID- 19103260
TI  - Activation in ventro-lateral prefrontal cortex during the act of tasting: an
      fNIRS study.
AB  - The act of tasting is the product of inseparable integrative behavior consisting
      of multi-sensory processing and orolingual motor coordination. Often tasting
      induced brain activity is looked at in a reductionist manner as a set of isolated
      components. However, brain activity as a whole during tasting may not simply be
      the sum of isolated brain responses; therefore, attempting to look at the
      cortical activation in a more holistic manner is important. Using functional near
      infrared spectroscopy (fNIRS), we assessed cortical responses during tasting,
      contrasting observed neuronal activation of the lateral prefrontal cortex (LPFC),
      of 19 healthy participants before and during tasting of 8ml of sweet-based
      solutions. To examine the activated brain structure, we estimated the anatomical
      regions of the measured location in standard brain space. We also included simple
      tongue tapping movement (TT) and word fluency (WF) tasks as comparative
      functional markers. Significant activity was found in channels (CHs) estimated to
      be in the bilateral oral motor areas during the TT task, and those in the LPFC,
      primarily in the left hemisphere, during the WF task. During the tasting task,
      significant activation was observed in CHs estimated to lie in the ventral part
      of pre- and post-central gyri as well as in the ventro-LPFC (VLPFC). The
      activated regions partly overlapped with those detected during TT or WF tasks,
      but extended more anteriorly and ventrally. Our study suggests that, in addition
      to tongue motor areas, the VLPFC is involved in the act of tasting.

PMID- 19103261
TI  - Novel allelic variants in the human serotonin transporter gene linked
      polymorphism (5-HTTLPR) among depressed patients with suicide attempt.
AB  - A polymorphism in the serotonin transporter gene (5-HTTLPR) is being extensively
      studied for association with suicidal behavior. A new allelic variant within the
      5-HTTLPR polymorphism was described but it has not been thoroughly analyzed in
      the recent literature. The SNP functional analysis demonstrated that the A
      variant of the L allele (L(A)) produces high levels of mRNA and that the G
      variant (L(G)) is equivalent to the S allele. Our aims were to compare the
      frequency of 5-HTTLPR alleles in 94 depressed patients who attempted suicide
      compared to 94 controls free of psychiatric disorder, including the embedded SNP
      rs25531. Using the biallelic classification, our sample contained 62 (33%) LL, 76
      (40.4%) LS, and 50 (26.6%) SS individuals. Using the functional classification
      system, our sample contained 43 (22.5%) L'L', 84 (44.7%) L'S', and 61 (32.4%)
      S'S' individuals, with no significant differences between cases and controls in
      genotypic tests in either biallelic (chi(2)=2.543; df=2; p=0.280) and functional
      models (chi(2)=2.995; df=2; p=0.228). The minor allele frequency (MAF) - the S
      allele - did not show any distributional difference between cases and controls
      using biallelic classification system 0.51 vs. 0.43, (OR=1.41; CI95% 0.94 to
      2.12; p=0.121). Also the S' allele of the functional classification system did
      not show any distributional difference between the two groups 0.59. vs. 0.51
      (OR=1.35; CI95% 0.90 to 2.03; p=0.178). This study provided the possibility of a
      re-analysis of novell 5-HTTLPR functional variants identified within L allele
      that alters its mRNA production and thus changes its functionality. We could not
      find any association between both biallelic and functional 5-HTTLPR in depressed
      patients with suicide attempt, being the small sample size an important
      limitation for these results. In conclusion, we can suggest that despite the
      several studies in this issue, the exact effect and role of 5-HTTLPR in genetics
      of suicide is still unclear and should be better investigated for future studies.

PMID- 19103262
TI  - Combination of deferoxamine and erythropoietin: therapy for hypoxia-ischemia
      induced brain injury in the neonatal rat?
AB  - Deferoxamine (DFO) and erythropoietin (EPO) have each been shown to provide
      neuroprotection in neonatal rodent models of brain injury. In view of the
      described anti-oxidative actions of DFO and the anti-apoptotic and anti
      inflammatory effects of EPO, we hypothesized that the combination of DFO and EPO
      would increase neuroprotection after neonatal hypoxic-ischemic brain injury as
      compared to single DFO or EPO treatment. At postnatal day 7 rats underwent right
      common carotid artery occlusion followed by a 90-min exposure to 8% oxygen. Rats
      were treated intraperitoneally with DFO (200mg/kg), recombinant human EPO (1
      kU/kg), a combination of DFO-EPO or vehicle at 0, 24 and 48 h after hypoxia
      ischemia (HI) and were sacrificed at 72 h. DFO-EPO administration reduced the
      number of cleaved caspase 3-positive cells in the ipsilateral cerebral cortex.
      Early neuronal damage was assessed by staining for microtubuli-associated protein
      (MAP)-2. In our model 63+/-9% loss of ipsilateral MAP-2 was observed after HI,
      indicating extensive brain injury. DFO, EPO or DFO-EPO treatment did not improve
      neuronal integrity as defined by MAP-2. Cerebral white matter tracts were stained
      for myelin basic protein (MBP), a constituent of myelin. Hypoxia-ischemia
      strongly reduced MBP staining which suggests white matter damage. However, DFO,
      EPO and DFO-EPO treatment had no effect on the loss of MBP staining. Finally, HI
      induced loss of striatal tyrosine hydroxylase staining was not attenuated by DFO,
      EPO or DFO-EPO. Although DFO-EPO treatment reduced the number of cleaved caspase
      3(+) cells, treatment with DFO, EPO, or with the combination of DFO and EPO did
      not protect against gray or white matter damage in the experimental setting
      applied.

PMID- 19103263
TI  - Oxidative inactivation of lactonase activity of purified human paraoxonase 1
      (PON1).
AB  - Paraoxonase1 (PON1), one of HDL-associated antioxidant proteins, is known to lose
      its activity in vivo systems under oxidative stress. Here, we examined the effect
      of various oxidants on lactonase activity of PON1, and tried to protect the
      lactonase activity from oxidative inactivation. Among the oxidative systems
      tested, the ascorbate/Cu(2+) system was the most potent in inactivating the
      lactonase activity of purified PON1; in contrast to a limited role of Fe(2+),
      Cu(2+) (0.05-1.0 microM) remarkably enhanced the inactivation of PON1 in the
      presence of ascorbate (0.02-0.1 mM). Moreover, Cu(2+) alone inhibited the
      lactonase activity at concentrations as low as 1 microM. The ascorbate/Cu(2+)
      mediated inactivation of PON1 lactonase activity was prevented by catalase, but
      not general hydroxyl radical scavengers, suggesting the implication of Cu(2+)
      bound hydroxyl radicals in the oxidative inactivation. Compared to arylesterase
      activity, lactonase activity appears to be more sensitive to Cu(2+)-catalyzed
      oxidation. Separately, ascorbate/Cu(2+)-mediated inactivation of lactonase
      activity was prevented by oleic acid as well as phoshatidylcholine. Taken
      together, our data demonstrate that Cu(2+)-catalyzed oxidation may be a primary
      factor to cause the decrease of PON1 lactonase activity under oxidative stress
      and that lactonase activity of PON1 is most susceptible to ascorbate/Cu(2+) among
      PON1 activities. In addition, we have showed that radical-induced inactivation of
      lactonase activity is prevented by some lipids.

PMID- 19103264
TI  - Involvement of exon 6-mediated calpastatin intracellular movements in the
      modulation of calpain activation.
AB  - BACKGROUND: To establish the physiological role of calpain, it is necessary to
      define how the protease can escape from the effect of its natural inhibitor
      calpastatin, since both proteins co-localize into the cell cytosol. METHODS: To
      answer this question, we have overexpressed four fluorescent calpastatin
      constructs, differing in the composition of their XL- and L-domains, and the
      intracellular trafficking of this protein inhibitor has been followed by single
      cell fluorescence imaging. RESULTS AND CONCLUSIONS: By the use of these
      calpastatin forms differing in the type of exon-derived sequences contained in
      the XL- and L-domains, we have demonstrated that the sequence coded by exon 6,
      containing multiple phosphorylation sites, is directly involved in determining
      the cell localization of calpastatin. In fact, exposure to cAMP promotes the
      recruitment into aggregates of those calpastatin forms containing the exon 6
      sequence. These protein movements are directly related to the level of cytosolic
      inhibitory capacity and thereby to the extent of intracellular calpain
      activation. GENERAL SIGNIFICANCE: The recruitment of calpastatin into aggregates
      allows the translocation and activation of the protease to the membranes; on the
      contrary, the presence of large amounts of calpastatin in the cytosol prevents
      both processes, protecting the cell from undesired proteolysis.

PMID- 19103265
TI  - Boosting T-cell immunity as a therapeutic approach for neurodegenerative
      conditions: the role of innate immunity.
AB  - Our research group has been working for more than a decade on the cross-talk
      between the immune and the nervous systems. Due to the unique nature of the
      central nervous system (CNS) as an immune privileged site, it was commonly
      believed that the nervous system functions optimally without any immune
      intervention, and that any immune cell infiltration to the CNS is a sign of
      pathology. However, since the immune system constitutes the body's major defense
      and repair mechanism, it seemed unreasonable that the CNS would have completely
      lost the need for assistance from this system. This insight prompted us to
      revisit the entire question of whether immune cells are required for recovery
      from CNS injuries. We subsequently made numerous fundamental observations that
      led us to formulate a unified theory linking all neurodegenerative conditions;
      thus, we suggested that "T-cell immunity to self maintains the self," at least in
      the CNS. According to this view, immunity to self ("protective autoimmunity")
      provides a pivotal role in maintenance, protection, and repair of the healthy and
      diseased CNS. We further showed that the T cells mediate their effect, at least
      under pathological conditions, by controlling the recruitment of blood-borne
      monocytes, which play a crucial local role that cannot be replaced by the
      resident microglia. Boosting of such a T cell response specific for brain
      proteins, while carefully choosing the antigen, the carrier, timing, dosing, and
      regimen should be considered as a way of augmenting a physiological repair
      mechanism needed to ameliorate disease conditions while restoring equilibrium
      needed for protection, repair and renewal; such therapy is not intended to modify
      a single mediator of a single disease, but rather, would serve as an approach for
      adjusting the levels of the immune response needed to restore a lost balance.

PMID- 19103266
TI  - Trichostatin A enhances OGD-astrocyte viability by inhibiting inflammatory
      reaction mediated by NF-kappaB.
AB  - In this study we investigate the protective effects of Trichostatin A (TSA) on
      astrocyte injury after oxygen-glucose deprivation (OGD) and further explore its
      possible protective mechanisms of inhibiting inflammatory reaction mediated by
      nuclear factor-kappaB (NF-kappaB). In the in vitro model of astrocyte OGD, TSA
      treatment was used at different doses and time points before deprivation.
      Astroglial viability was determined by MTT assay. Then tumor necrosis factor
      alpha, interleukin-1beta (IL-1beta), and IL-6 mRNA were measured by RT-PCR.
      Furthermore, the expression of phosphorylated p65, mitogen-activated protein
      kinase (MAPK)/extracellular signal-regulated kinases (ERK), MAPK/c-Jun N-terminal
      (JNK) and MAPK/p38 was assayed by Western blot. The results showed that TSA at
      the five doses (12.5, 25, 50, 100, and 200 ng/ml) significantly enhanced the
      astrocytes viability by 25.3%, 46.1%, 37.5%, 34.9%, and 22% of the vehicle,
      respectively. The level of TNF-alpha, IL-1beta and IL-6 mRNA in astrocytes was
      increased after OGD and down-regulated by TSA (p<0.05). In addition, the
      phosphorylation p65 was markedly activated in the astrocytes after OGD compared
      to the control (p<0.05). TSA inhibited phosphorylation of p65 but did not affect
      the MAPK pathway. Our results suggest that TSA protects astrocytes from damage
      after OGD by the inhibition of the inflammatory reaction and this protection is
      at least partially through the suppression of phosphorylation of NF-kappaB p65.

PMID- 19103267
TI  - Substance P expression in the distal cerebrospinal fluid-contacting neurons and
      spinal trigeminal nucleus in formalin-induced the orofacial inflammatory pain in
      rats.
AB  - The distal cerebrospinal fluid-contacting neuron (dCSF-CN) is a peculiar type of
      neuron whose body is in the parenchyma of the brain and processes extend into
      cerebrospinal fluid (CSF) in the cavity of the ventricle in the central nervous
      system. Because most of the dCSF-CNs are found in the dorsal raphe nucleus (DR)
      of the brainstem, we presume these neurons relate to pain modulation. Many
      experiments have demonstrated that substance P (SP) plays an important role in
      the development of pain and hyperalgesia. To explore whether the dCSF-CNs
      modulated the orofacial inflammatory pain in rats, we examined behavioral changes
      with the orofacial formalin test and SP-expression in the dCSF-CNs and spinal
      trigeminal nucleus (STN) with dual immunohistochemical labeling for light
      microscopy or immunoelectron microscopy. It is revealed that 2h after 2.5%
      formalin injection SP-expression in the dCSF-CNs and STN is upregulated
      significantly, which may be considered an important role for nociceptive
      processing.

PMID- 19103268
TI  - Prefrontal afferents to the dorsal raphe nucleus in the rat.
AB  - The prefrontal cortex (PFC) receives strong inputs from monoaminergic cell groups
      in the brainstem and also sends projections to these nuclei. Recent evidence
      suggests that the PFC exerts a powerful top-down control over the dorsal raphe
      nucleus (DR) and that it may be involved in the actions of pharmaceutical drugs
      and drugs of abuse. In the light of these findings, the precise origin of
      prefrontal inputs to DR was presently investigated by using the cholera toxin
      subunit b (CTb) as retrograde tracer. All the injections placed in DR produced
      retrograde labeling in the medial, orbital, and lateral divisions of the PFC as
      well as in the medial part of the frontal polar cortex. The labeling was
      primarily located in layer V. Remarkably, labeling in the medial PFC was denser
      in its ventral part (infralimbic and ventral prelimbic cortices) than in its
      dorsal part (dorsal prelimbic, anterior cingulate and medial precentral
      cortices). After injections in the rostral or caudal DR, the largest number of
      labeled neurons was observed in the medial PFC, whereas after injections in the
      mid-rostrocaudal DR, the labeled neurons were more homogeneously distributed in
      the three main PFC divisions. A cluster of labeled neurons also was observed
      around the apex of the rostral pole of the accumbens, especially after rostral
      and mid-rostrocaudal DR injections. Overall, these results confirm the existence
      of robust prefrontal projections to DR, mainly derived from the ventral part of
      the medial PFC, and underscore a substantial contribution of the frontal polar
      cortex.

PMID- 19103269
TI  - Investigating social discrimination of group members by laying hens.
AB  - Social relationships in domestic fowl are commonly assumed to rely on social
      recognition and its pre-requisite, discrimination of group-mates. If this is
      true, then the unnatural physical and social environments in which commercial
      laying hens are typically housed, when compared with those in which their
      progenitor species evolved, may compromise social function with consequent
      implications for welfare. Our aims were to determine whether adult hens can
      discriminate between unique pairs of familiar conspecifics, and to establish the
      most appropriate method for assessing this social discrimination. We investigated
      group-mate discrimination using two learning tasks in which there was bi
      directional exchange of visual, auditory and olfactory information. Learning
      occurred in a Y-maze task (p<0.003; n=7/8) but not in an operant key-pecking task
      (p=0.001; n=1/10). A further experiment with the operant-trained hens examined
      whether failure was specific to the group-mate social discrimination or to the
      response task. Learning also failed to occur in this familiar/unfamiliar social
      discrimination task (p=0.001; n=1/10). Our findings demonstrate unequivocally
      that adult laying hens kept in small groups, under environmental conditions more
      consistent with those in which sensory capacities evolved, can discriminate group
      members: however, appropriate methods to demonstrate discrimination are crucial.

PMID- 19103270
TI  - Effect of 2-amino-9H-pyrido[2,3-b]indole (AalphaC), a carcinogenic heterocyclic
      amine present in food, on atherosclerotic plaque development in apoE deficient
      mice.
AB  - There is experimental and epidemiological evidence demonstrating that polycyclic
      aromatic hydrocarbons (PAHs) are involved in the pathogenesis of cardiovascular
      diseases. However, heterocyclic amines (HAs), a class of carcinogenic compounds
      present in food, which share many biochemical features with PAHs, have not
      received much attention. Previous reports have shown that the heterocyclic amine
      2-amino-9H-pyrido[2,3-b]indole (AalphaC) binds and metabolically affects
      endothelial cells in animal models suggesting a potential role in vascular
      remodeling. The present study investigates the effect of exposure to HAs on
      atherosclerotic plaque development in the apoE(-/-) mice. We observed that
      animals treated with AalphaC developed atherosclerotic lesions characterized by
      lower lipid content but richer in inflammatory cells and collagen content when
      compared with control animals. Moreover, atherosclerotic plaques from AalphaC
      treated apoE(-/-) mice were also smaller with a marked reduction in the tunica
      media thickness. Furthermore, total cholesterol levels were significantly reduced
      in AalphaC-treated apoE(-/-) mice. In contrast to what has been previously
      reported for PAHs, we provide for the first time evidence that HAs may protect
      against cardiovascular disease by inducing stable atherosclerotic plaques and
      reducing circulating cholesterol levels. These results open new avenues to
      further investigate the role of these food-borne carcinogens in cardiovascular
      physiology and pathology.

PMID- 19103271
TI  - Interferon alpha delivery systems for the treatment of hepatitis C.
AB  - Hepatitis C virus (HCV) infections are the most common chronic blood-borne viral
      infections in the world. The prevalence of HCV infections varies significantly by
      race or ethnicity, with a high prevalence of the disease displayed in the
      Hispanic population. Additionally, Hispanics with chronic HCV have also more
      advanced hepatic fibrosis and faster liver fibrosis progression rates than either
      African Americans or Caucasians. Furthermore, a higher prevalence of cirrhosis
      and extent of mortality from liver cirrhosis is also observed in the Hispanic
      population compared with other groups. Current recommendations for treatment of
      hepatitis C are interferon alpha (IFNalpha)-based monotherapy and combination of
      IFNalpha preparations with ribavirin. Future treatment regimens will still be
      based on IFNalpha therapy with or without other effective antiviral agents,
      currently under investigation. However, there are some inherent limitations,
      mainly their relative short systemic circulation lifespan, and their unwanted
      effects on some non-target tissues. New research focuses on the development of
      novel modified interferon molecules which demonstrate reduced side effects and
      extended systemic circulation time, which can ultimately provide greater
      efficacy. Alternative routes for IFNalpha delivery, such as oral delivery,
      demonstrate challenging but promising areas of research for improving future
      patient compliance.

PMID- 19103272
TI  - Effect of Pinus massoniana bark extract on IFN-gamma-induced ICAM-1 expression in
      HaCaT human keratinocytes.
AB  - AIMS OF THE STUDY: Pinus massoniana bark extract (PMBE) with known anti-oxidant
      activity is comprised of various flavonoids including several bioactive
      compounds. We found that PMBE contains 1.27% taxifolin, a well-studied compound
      with known anti-inflammatory activity. Therefore, in the present study, we
      evaluated the effects of PMBE and taxifolin on intercellular adhesion molecule-1
      (ICAM-1) expression. MATERIALS AND METHODS: PMBE and taxifolin were prepared.
      After HaCaT cells were pre-treatmented with PMBE and taxifolin, HaCaT cells were
      treatmented with 1000 U/ml IFN-gamma for 24 h. RESULTS: Treatment of HaCaT cells
      with 1000 U/ml IFN-gamma for 24 h markedly increased ICAM-1 expression. However,
      PMBE pre-treatment (40 microg/ml for 24 h) significantly inhibited IFN-gamma
      induced ICAM-1 expression. In equal concentrations of taxifolin, PMBE-mediated
      inhibition of ICAM-1 mRNA and protein expression was greater than taxifolin
      mediated-inhibition, and the front on inhibition of ICAM-1 protein expression was
      2.24-2.30-fold of the latter. When cells were treated with both compounds at a
      concentration of 40 microg/ml, PMBE-mediated inhibition of ICAM-1 mRNA was also
      greater than taxifolin-mediated inhibition and PMBE on inhibition of ICAM-1
      protein expression was 2.60-3.00-fold the inhibition mediated by taxifolin.
      CONCLUSIONS: PMBE including additional bioactive compounds may possibly synergize
      to inhibit transcription and translation of inducible ICAM-1expression and PMBE
      was greater than monomeric flavonoid taxifolin. These results indicate that PMBE
      exhibits great potential as a therapeutic treatment for inflammatory skin
      diseases.

PMID- 19103273
TI  - Astragalus membranaceus flavonoids (AMF) ameliorate chronic fatigue syndrome
      induced by food intake restriction plus forced swimming.
AB  - AIM OF THE STUDY: Alteration of immune function may be associated with chronic
      fatigue syndrome (CFS) and this study reveals the immunoregulatory effect of
      Astragalus membranaceus flavonoids (AMF). MATERIALS AND METHODS: CF rats were
      induced by food intake restriction plus forced swimming for 6 weeks. RESULTS: An
      atrophied spleen associated with a significantly decreased spleen/body weight
      ratio and a reduced spleen cells proliferation was found in CF rats when compared
      with home cage controls. AMF given orally at 20, 50 and 100 mg/kg body weight
      once a day consecutively for 6 weeks could recover the reduced cell
      proliferation. A switch to Th1-dominated immune regulation was observed in CF
      rats as the cultured splenocytes produced more interleukin-2 (IL-2) but less IL-4
      when compared with controls. Supplementation with AMF could significantly
      counteract the aberrant cytokine production and rats received AMF exhibited
      higher endurance capacity to swim when compared with those without AMF
      administration. Checking the spectrum signals confirmed that the three major
      isoflavones contained in AMF were ononin, formononetin, and
      demethylhomopterocarpin. CONCLUSION: Alterations of immune function may be
      associated with CFS and the tonic effects of AMF against CF may be attributable
      to balance the abnormal cytokine level by isoflavones.

PMID- 19103274
TI  - Biosorbents for heavy metals removal and their future.
AB  - A vast array of biological materials, especially bacteria, algae, yeasts and
      fungi have received increasing attention for heavy metal removal and recovery due
      to their good performance, low cost and large available quantities. The
      biosorbent, unlike mono functional ion exchange resins, contains variety of
      functional sites including carboxyl, imidazole, sulphydryl, amino, phosphate,
      sulfate, thioether, phenol, carbonyl, amide and hydroxyl moieties. Biosorbents
      are cheaper, more effective alternatives for the removal of metallic elements,
      especially heavy metals from aqueous solution. In this paper, based on the
      literatures and our research results, the biosorbents widely used for heavy metal
      removal were reviewed, mainly focusing on their cellular structure, biosorption
      performance, their pretreatment, modification, regeneration/reuse, modeling of
      biosorption (isotherm and kinetic models), the development of novel biosorbents,
      their evaluation, potential application and future. The pretreatment and
      modification of biosorbents aiming to improve their sorption capacity was
      introduced and evaluated. Molecular biotechnology is a potent tool to elucidate
      the mechanisms at molecular level, and to construct engineered organisms with
      higher biosorption capacity and selectivity for the objective metal ions. The
      potential application of biosorption and biosorbents was discussed. Although the
      biosorption application is facing the great challenge, there are two trends for
      the development of the biosorption process for metal removal. One trend is to use
      hybrid technology for pollutants removal, especially using living cells. Another
      trend is to develop the commercial biosorbents using immobilization technology,
      and to improve the biosorption process including regeneration/reuse, making the
      biosorbents just like a kind of ion exchange resin, as well as to exploit the
      market with great endeavor.

PMID- 19103275
TI  - Cross-fostering effect on postnatal development of rat pups exposed to
      methamphetamine during gestation and preweaning periods.
AB  - There are studies showing that drug abuse during pregnancy may have a long-term
      effect on progeny of drug-abusing mothers. Our previous work demonstrated that
      prenatal and/or postnatal methamphetamine injections impair maternal behavior.
      The purpose of the present study was to assess the effect of prenatal
      methamphetamine or stress exposure and postnatal breeding on postnatal
      development of rat pups. Female rats were injected with methamphetamine (5 mg/kg
      daily) or physiological saline prior, during and after gestation. Absolute
      controls did not receive any injections. On postnatal day 1, pups were cross
      fostered so that each mother received some of her own and some of the pups from
      the mothers with the other two treatments. Pups were weighted daily for the
      entire lactation period. Postural motor reaction development was examined daily
      by righting reflex between postnatal day 1 and 12. On postnatal day 15 homing
      test examining pups' nest-seeking behavior was performed. On postnatal day 23
      rotarod and bar-holding tests were used to investigate sensorimotor coordination
      of pups. We demonstrated that prenatal methamphetamine exposure impairs
      performance of sensorimotor tests (righting reflex on surface and rotarod test).
      Moreover, the effect of methamphetamine as well as the effect of prenatal stress
      induced by saline injections was affected by postnatal breeding conditions in
      sensorimotor tests as well as in the test of homing. Our results support the
      hypothesis that the variation in rat maternal care could serve as a mechanism for
      a nongenomic behavioral mode of transmission of traits.

PMID- 19103276
TI  - Analysis of the sfaX(II) locus in the Escherichia coli meningitis isolate IHE3034
      reveals two novel regulatory genes within the promoter-distal region of the main
      S fimbrial operon.
AB  - We describe the expression and regulation of the gene sfaX(II) located near the
      Sfa(II) fimbrial determinant in the newborn meningitis Escherichia coli (NMEC)
      isolate IHE3034. sfaX(II) belongs to a gene family, the 17-kDa genes, typically
      located downstream (300-3000bp) of different fimbrial operons found in E. coli
      isolates of uropathogenic and newborn meningitis origin. Using transcriptional
      sfaX(II) reporter gene fusions we found that different environmental conditions
      commonly affecting expression of fimbrial genes also affected sfaX(II)
      expression. Analysis of the sfaX(II) transcripts showed that the gene is part of
      the main fimbrial operon as it is transcribed together with the rest of the
      fimbrial genes. In addition, the sfaX(II) gene can be expressed from a more
      proximal promoter and is found to be subject to strong down-regulation by the
      nucleoid protein H-NS. Studies with an sfaX(II) mutant derivative of IHE3034 did
      not reveal effects on Sfa(II) fimbrial biogenesis as monitored by e.g.
      immunofluorescence microscopy. Nevertheless, a mutation in sfaX(II) resulted in
      altered expression of other surface components. Moreover, we define a new gene,
      sfaY(II), coding for a putative phosphodiesterase that is located in between the
      sfaX(II) gene and the fimbrial biogenesis genes. Our studies by ectopic
      expression of sfaY(II) in Vibrio cholerae showed that the gene product caused
      reduced biofilm formation and it is proposed that sfaY(II) can influence cyclic
      di-GMP turnover in the bacteria. Our findings demonstrate that the operons
      typical for S-fimbriae of extraintestinal pathogenic E. coli include previously
      unrecognized novel regulatory genes.

PMID- 19103277
TI  - Predicted gene sequence C10orf112 is transcribed, exhibits tissue-specific
      expression, and may correspond to AD7.
AB  - Case-control and prospective longitudinal studies have revealed an interaction of
      the anonymous D10S1423 234 bp allele with the APOE4 allele in determining the age
      specific risk of Alzheimer's disease (AD). The D10S1423 polymorphism resides
      within intron 10 of open reading frame C10orf112, whose predicted product
      resembles a low-density lipoprotein receptor (NCBI Build 35.1). These
      observations suggest that the D10S1423 234 bp allele may be in linkage
      disequilibrium with a C10orf112 gene variant whose product interacts with the
      apoE4 lipoprotein. Our initial exploration of this hypothesis focused on
      validating the C10orf112 gene model. RT-PCR amplification from human hippocampal
      mRNA confirmed that 34 of the predicted 39 exons of C10orf112 were expressed in
      this brain region. Northern blots revealed 1.2 kb and 3.2 kb mRNA species that
      hybridize to a cDNA probe consisting of contiguous exons 23-26. Expression of
      these C10orf112 mRNA species was limited to a subset of brain regions and heart
      tissue.

PMID- 19103278
TI  - Comparative analyses of distributions and functions of Z-DNA in Arabidopsis and
      rice.
AB  - Left-handed Z-DNA is an energetically unfavorable DNA structure that could form
      mostly under certain physiological conditions and was known to be involved in a
      number of cellular activities such as transcription regulation. We have compared
      the distributions and functions of Z-DNA in the genomes of Arabidopsis and rice,
      and observed that Z-DNA occurs in rice at least 9 times more often than in
      Arabidopsis; similar observations hold for other monocots and dicots. In
      addition, Z-DNA is significantly enriched in the coding regions of Arabidopsis,
      and in the high-GC-content regions of rice. Based on our analyses, we speculate
      that Z-DNA may play a role in regulating the expression of transcription factors,
      inhibitors, translation repressors, succinate dehydrogenases and glutathione
      disulfide reductases in Arabidopsis, and it may affect the expression of vesicle
      and nucleosome genes and genes involved in alcohol transporter activity, stem
      cell maintenance, meristem development and reproductive structure development in
      rice.

PMID- 19103279
TI  - The safety of conception occurring shortly after methotrexate treatment of an
      ectopic pregnancy.
AB  - The objective of this study was to determine whether a single or repeated
      injection of methotrexate (MTX) to treat ectopic pregnancy results in either
      teratogenicity or other bad obstetric outcome in the pregnancy that shortly
      follows treatment. Data were retrieved from the medical records of 314 women
      treated with MTX for ectopic pregnancy in our institute (2000-2006) included age,
      MTX dosage, interval between last MTX treatment to conception, results of
      ultrasonographic follow-up of the subsequent pregnancy, triple test, karyotype
      testing, pregnancy outcome, and newborn weight and Apgar score. A logistic
      regression model based on pregnancy outcome as the dependent variable and
      interval since last MTX treatment as the independent variable estimated the odds
      ratio for the safety of conception occurring shortly after the treatment.
      Complete information was obtained for 125 pregnancies. Forty-five pregnancies
      occurred within 6 months (mean 3.6+/-1.7) after the last MTX treatment. The
      outcome of these pregnancies was compared with that of 80 pregnancies which
      occurred > or =6 months (mean 23.6+/-14.7) after the last MTX treatment. The
      fetal malformation and adverse outcome rates for both groups were similar (odds
      ratio 1.003, 95% CI 0.98-1.02). According to a logistic regression analysis, the
      interval between the last MTX treatment for ectopic pregnancy had no effect on
      the outcome of the pregnancy that shortly followed it. The results of this study
      support the notion that conceiving within the first 6 months after treatment with
      MTX for ectopic pregnancy is safe and not associated with any increase in the
      examined adverse pregnancy outcome parameters.

PMID- 19103280
TI  - Fetal growth restriction is related to placental levels of cadmium, lead and
      arsenic but not with antioxidant activities.
AB  - The objectives of this study were: to measure some essential metals and toxicants
      in placentas of mothers delivering neonates with fetal growth restriction, and to
      establish potential associations between environmental adverse stimulus and
      antioxidant protective mechanisms. Placentas of 20 mothers delivering neonates
      with low birth weight (<2500g) and normal birth weight (>3000g) at term were
      collected. Placental concentration of zinc, mercury, selenium and arsenic were
      measured by Instrumental Neutron Activation Analysis (INAA), and iron, copper,
      cadmium and lead by Atomic Absorption Spectrometry (AAS). Total glutathione,
      lipid peroxidation, total antioxidant activity and antioxidant enzyme activities
      (superoxide dismutase and glutathione peroxidase) were determined
      spectrophotometrically. Results showed reduced iron levels and increased
      concentrations of cadmium, lead and arsenic in placentas of mothers delivering
      low birth weight neonates, but not differences in oxidative stress parameters or
      antioxidant enzymatic activities, suggesting a relationship between low birth
      weight and placental concentration of cadmium, arsenic and lead.

PMID- 19103281
TI  - Green tea extract increases cyclophosphamide-induced teratogenesis by modulating
      the expression of cytochrome P-450 mRNA.
AB  - The effects of green tea extract (GTE) on the fetal development and external,
      visceral and skeletal abnormalities induced by cyclophosphamide were investigated
      in rats. Pregnant rats were daily administered GTE (100mg/kg) by gavage for 7 d,
      from the 6th to 12th day of gestation, and intraperitoneally administered with
      cyclophosphamide (11mg/kg) 1h after the final treatment. On the 20th day of
      gestation, maternal and fetal abnormalities were determined by Cesarian section.
      Cyclophosphamide was found to reduce fetal and placental weights without
      increasing resorption or death. In addition, it induced malformations in live
      fetuses; 94.6%, 41.5% and 100% of the external (skull and limb defects), visceral
      (cleft palate and ureteric dilatation) and skeletal (acrania, vertebral/costal
      malformations and delayed ossification) abnormalities. When pre-treated with GTE,
      cyclophosphamide-induced body weight loss and abnormalities of fetuses were
      remarkably aggravated. Moreover, repeated treatment with GTE greatly increased
      mRNA expression and activity of hepatic cytochrome P-450 (CYP) 2B, which
      metabolizes cyclophosphamide into teratogenic acrolein and cytotoxic
      phosphoramide mustard, while reducing CYP3A expression (a detoxifying enzyme).
      The results suggest that repeated intake of GTE may aggravate cyclophosphamide
      induced body weight loss and malformations of fetuses by modulating CYP2B and
      CYP3A.

PMID- 19103283
TI  - Rapid pre-clinical detection of classical swine fever by reverse transcription
      loop-mediated isothermal amplification.
AB  - The usefulness of reverse transcription loop-mediated isothermal amplification
      (RT-LAMP) for rapid pre-clinical detection of classical swine fever virus (CSFV)
      infection was evaluated. The RT-LAMP reaction could be finished in 60 min under
      isothermal condition at 65 degrees C by employing a set of four primers targeting
      the 5' untranslated region of CSFV. The RT-LAMP assay of CSFV showed higher
      sensitivities than that of RT-PCR, with a detection limit of 5 copies per
      reaction. No cross-reactivity was observed from the samples of other related
      viruses including porcine circovirus type 2, porcine parvovirus, porcine
      pseudorabies virus, Japanese encephalitis virus, and porcine reproductive and
      respiratory syndrome virus. The detection rates of CSFV RT-LAMP, RT-PCR and virus
      isolation for samples including blood, tonsil, nasal and rectal swabs from
      uninoculated pigs without any clear clinical symptom were 89%, 78% and 71%,
      respectively. Furthermore, all of the assays showed higher sensitivity for blood
      and tonsil swabs samples than nasal and rectal swabs. These results indicate that
      the CSFV RT-LAMP assay is a valuable tool for its rapid, cost-effective detection
      and has potential usefulness for rapid pre-clinical detection and surveillance of
      classical swine fever in developing countries.

PMID- 19103284
TI  - Human carotid atherosclerotic plaque increases oxidative state of macrophages and
      low-density lipoproteins, whereas paraoxonase 1 (PON1) decreases such atherogenic
      effects.
AB  - Human atherosclerotic plaque contains a variety of oxidized lipids, which can
      facilitate further oxidation. Paraoxonase 1 (PON1) is a high-density lipoprotein
      (HDL)-associated esterase (lipolactonase), exhibiting antiatherogenic properties.
      The aims of the present study were to examine the oxidizing potency of the human
      carotid plaque lipid extract (LE), and the antiatherogenic role of PON1 on LE
      oxidation competence. Human carotid plaques were extracted by organic solvent,
      and the extract was incubated with lipoprotein particles, with macrophages, or
      with probes sensitive to oxidative stress, with or without preincubation with
      PON1, followed by oxidative-stress assessment. Our findings imply that the LE
      oxidized LDL, macrophages, and exogenous probes and decreases HDL-mediated
      cholesterol efflux from macrophages, in a dose-dependent manner. Incubation of
      PON1 with LE significantly affects LE composition, reduces LE atherogenic
      properties, and decreases the extract's total peroxide concentration by 44%,
      macrophage oxidation by 25%, and probe oxidation by up to 52%. We conclude that
      these results expand our understanding of how the plaque itself accelerates
      atherogenesis and provides an important mechanism for attenuation of
      atherosclerosis development by the antioxidant action of PON1 on the
      atherosclerotic plaque.

PMID- 19103282
TI  - Dietary red clover (Trifolium pratense) induces oviduct growth and decreases
      ovary and testes growth in Japanese quail chicks.
AB  - To determine whether drought-stress alters phytoestrogens in red clover and
      whether red clover in the diet influences sexual development in Japanese quail,
      we fed chicks diets containing irrigated or non-irrigated clover. Irrigation
      altered phytoestrogenic activity of red clover (determined using an in vitro
      bioassay), with extracts of irrigated clover diet containing more estrogenic
      activity than extracts of non-irrigated clover diet. Chick growth was negatively
      correlated with the amount of irrigated or non-irrigated clover in the diet.
      Dietary red clover also depressed both absolute and relative gonad weights;
      however, relative oviduct weight was increased by the irrigated diet. Diets did
      not affect serum vitellogenin. These results reveal a negative influence of
      drought-stress on phytoestrogenic potency of clover, and that red clover in the
      diet can inhibit avian growth and development independent of irrigation state.
      Thus, phytoestrogens may affect reproductive development in wild birds, and
      environmental stressors may influence levels of phytoestrogens in the field.

PMID- 19103286
TI  - The effects of lipophilic substances on the shape of erythrocytes demonstrated by
      a new in vitro-method.
AB  - Low aqueous solubility of lipophilic agents, such as free fatty acids, hampers
      proper in vitro demonstration of biological effects, yielding an ambiguous in
      vitro-in vivo correlation. We have therefore developed a method for evaluating
      the acute effects of lipophilic substances on the shape of erythrocytes and
      estimated EC(50) and Hill coefficient according to the sigmoidal E(max) model.
      The test substance dissolved in medium-chain triglyceride is coated on a
      polycarbonate slide which serves as a cover sheet of a Burker chamber. Freshly
      collected finger-tip blood is diluted with autologous EDTA-plasma and introduced
      into the chamber. After 10min at 37 degrees C, the cells are photographed under
      microscope and the fractions of normal and defect cells are evaluated. No
      staining is needed and the cells are kept viable during the test period. With
      increasing chain length, fatty acids, aliphatic amines and alcohols all increased
      the fraction of defect erythrocytes in a concentration-dependent manner. The
      results indicate that several fatty acids are very potent in their acute actions
      on erythrocytes, and that this effect is due to chain length rather than
      conformation. CONCLUSION: The technique offers a screening method for testing the
      harmful effects of small amounts of lipophilic substances on erythrocytes.

PMID- 19103285
TI  - Superoxide constricts rat pulmonary arteries via Rho-kinase-mediated Ca(2+)
      sensitization.
AB  - Reactive oxygen species play a key role in vascular disease, pulmonary
      hypertension, and hypoxic pulmonary vasoconstriction. We investigated contractile
      responses, intracellular Ca(2+) ([Ca(2+)](i)), Rho-kinase translocation, and
      phosphorylation of the regulatory subunit of myosin phosphatase (MYPT-1) and of
      myosin light chain (MLC(20)) in response to LY83583, a generator of superoxide
      anion, in small intrapulmonary arteries (IPA) of rat. LY83583 caused
      concentration-dependent constrictions in IPA and greatly enhanced submaximal
      PGF(2alpha)-mediated preconstriction. In small femoral or mesenteric arteries of
      rat, LY83583 alone was without effect, but it relaxed a PGF(2)alpha-mediated
      preconstriction. Constrictions in IPA were inhibited by superoxide dismutase and
      tempol, but not catalase, and were endothelium and guanylate cyclase independent.
      Constrictions were also inhibited by the Rho-kinase inhibitor Y27632 and the Src
      family kinase inhibitor SU6656. LY83583 did not raise [Ca(2+)](i), but caused a
      Y27632-sensitive constriction in alpha-toxin-permeabilized IPA. LY83583 triggered
      translocation of Rho-kinase from the nucleus to the cytosol in pulmonary artery
      smooth muscle cells and enhanced phosphorylation of MYPT-1 at Thr-855 and of
      MLC(20) at Ser-19 in IPA. This enhancement was inhibited by superoxide dismutase
      and abolished by Y27632. Hydrogen peroxide did not activate Rho-kinase. We
      conclude that in rat small pulmonary artery, superoxide triggers Rho-kinase
      mediated Ca(2+) sensitization and vasoconstriction independent of hydrogen
      peroxide.

PMID- 19103287
TI  - Characterisation of the R3/1 cell line as an alveolar epithelial cell model for
      drug disposition studies.
AB  - The rat cell line R3/1 displays several phenotypical features of alveolar
      epithelial type I cells. In order to evaluate this cell line as potential in
      vitro model for drug disposition studies, R3/1 cells were cultured on Transwell
      filters and the transepithelial electrical resistance (TEER) was measured to test
      the integrity of cell layers. The mRNA expression of cell junctional components
      including E-cadherin, occludin, ZO-1 and ZO-2 was studied using reverse
      transcriptase-polymerase chain reaction (RT-PCR) and the corresponding proteins
      by immunofluorescence microscopy (IFM). Moreover, the expression pattern of
      catabolic peptidases, carboxypeptidase M, aminopeptidases (AP): A, B, N and P,
      gamma-glutamyltransferase (GGT), dipeptidylpeptidase IV, angiotensin-converting
      enzyme (ACE), and endopeptidases (EP) 24.11 and 24.15 was analysed in R3/1 cells
      and compared to rat alveolar epithelial I-like cells in primary culture. TEER
      peaked at 99+/-17Omegacm(2) after 5 days in culture. Addition of 0.1muM
      dexamethasone (DEX) with 20% foetal bovine serum further increased TEER by 65%.
      However, none of the culture conditions used in our study yielded monolayers with
      TEER values comparable to those of primary cultures of rat pneumocytes. No
      transcripts encoding for E-cadherin and occludin were detected by RT-PCR.
      However, ZO-1 and -2 mRNA transcripts were found. IFM using a monoclonal antibody
      against occludin confirmed the absence of the protein in R3/1 cells. Of the
      investigated proteolytic enzymes, mRNA transcripts encoding APA and APB as well
      as EP 24.11 and EP 24.15 were detected; a pattern similar to that of rat alveolar
      epithelial I-like cells in primary culture. Thus, although R3/1 cells express
      certain markers typical for type I pneumocytes (e.g., T1alpha, ICAM-1, connexin
      43, caveolins-1 and -2) they do not form electrically tight monolayers. This
      excludes R3/1 cells from being used as an in vitro model for alveolar absorption.
      However, the cell line may be suitable to study stability of inhaled and
      endogenous proteins.

PMID- 19103288
TI  - Diversity and evolutionary origins of fungi associated with seeds of a
      neotropical pioneer tree: a case study for analysing fungal environmental
      samples.
AB  - Fungi associated with seeds of tropical trees pervasively affect seed survival
      and germination, and thus are an important, but understudied, component of forest
      ecology. Here, we examine the diversity and evolutionary origins of fungi
      isolated from seeds of an important pioneer tree (Cecropia insignis,
      Cecropiaceae) following burial in soil for five months in a tropical moist forest
      in Panama. Our approach, which relied on molecular sequence data because most
      isolates did not sporulate in culture, provides an opportunity to evaluate
      several methods currently used to analyse environmental samples of fungi. First,
      intra- and interspecific divergence were estimated for the nu-rITS and 5.8S gene
      for four genera of Ascomycota that are commonly recovered from seeds. Using these
      values we estimated species boundaries for 527 isolates, showing that seed
      associated fungi are highly diverse, horizontally transmitted, and genotypically
      congruent with some foliar endophytes from the same site. We then examined
      methods for inferring the taxonomic placement and phylogenetic relationships of
      these fungi, evaluating the effects of manual versus automated alignment, model
      selection, and inference methods, as well as the quality of BLAST-based
      identification using GenBank. We found that common methods such as neighbor
      joining and Bayesian inference differ in their sensitivity to alignment methods;
      analyses of particular fungal genera differ in their sensitivity to alignments;
      and numerous and sometimes intricate disparities exist between BLAST-based versus
      phylogeny-based identification methods. Lastly, we used our most robust methods
      to infer phylogenetic relationships of seed-associated fungi in four focal
      genera, and reconstructed ancestral states to generate preliminary hypotheses
      regarding the evolutionary origins of this guild. Our results illustrate the
      dynamic evolutionary relationships among endophytic fungi, pathogens, and seed
      associated fungi, and the apparent evolutionary distinctiveness of saprotrophs.
      Our study also elucidates the diversity, taxonomy, and ecology of an important
      group of plant-associated fungi and highlights some of the advantages and
      challenges inherent in the use of ITS data for environmental sampling of fungi.

PMID- 19103289
TI  - Dihydrotestosterone and estradiol-17beta mutually neutralize their inhibitory
      effects on human vascular smooth muscle cell growth in vitro.
AB  - We reported previously that high concentrations of either estradiol-17beta (E(2))
      or dihydrotestosterone (DHT) inhibit growth of human cultured vascular smooth
      muscle cells (VSMC), mediated by cell membrane receptors and MAP-kinase-kinase
      activity (MEK). We now tested whether the presence of the opposite gender's
      dominant sex hormone modifies these effects. We incubated VSMC with various
      concentrations of E(2) and DHT or protein bound hormones (E(2)-BSA or T-BSA),
      alone or in various combinations. High concentration of E(2) or E(2)-BSA
      inhibited VSMC growth and stimulated MEK. In the presence of 3 nM DHT, high
      concentration of E(2) no longer inhibited (3)[H] thymidine incorporation or
      increased MEK. Moreover, when high DHT concentration (300 nM) was added to VSMC
      exposed to high E(2), VSMC growth actually increased without change in MEK. DHT
      at 300 nM suppressed VSMC growth and increased MEK while 0.3 nM E(2) had only
      marginal effect on this interaction, and 30 nM E(2) reversed the inhibitory
      effect of DHT on cell growth. The inhibitory effects of both E(2) and DHT on VSMC
      cell growth and the stimulation of MEK was apparently mediated by cell membrane
      receptors, as it persisted when bovine serum albumin (BSA)-bound hormones were
      used. Further, inhibition of VSMC growth induced by E(2)-BSA was reversed in the
      presence of T-BSA and vice versa. These results suggest that while female and
      male sex hormones affect VSMC growth similarly, they interfere in a dose-,
      hormone- and MEK-dependent manner with each other's effect.

PMID- 19103290
TI  - 8-Prenylnaringenin inhibits epidermal growth factor-induced MCF-7 breast cancer
      cell proliferation by targeting phosphatidylinositol-3-OH kinase activity.
AB  - 8-Prenylnaringenin (8PN), one of the strongest plant-derived oestrogen receptors
      (ERs) ligand, has been suggested to have potential cancer chemo-preventive
      activities and anti-angiogenic properties. Because published data suggest that
      ERs serve as nodal point that allows interactions between hormones and growth
      factors mediated pathways, we decided to investigate the effects exerted by 8PN
      on Epidermal growth factor (EGF)-elicited pathways in breast cancer cells. Here
      we show that in ER positive MCF-7 cells, 8PN interferes with EGF induced cell
      proliferation by strongly inhibiting activation of PI(3)K/Akt pathway, without
      affecting EGFR expression or tyrosine phosphorylation, and exerting a synergistic
      activation of Erk1/2 phosphorylation. Moreover, we demonstrate that 8PN is a
      direct inhibitor of PI(3)K activity as it is shown by in vitro experiments with
      the purified enzyme and by its inability to impair serine phosphorylation of a
      constitutive active form of Akt. These findings suggest that inhibition of PI(3)K
      is a novel mechanism which contributes to 8PN activity to inhibit cancer cell
      survival and EGF induced proliferation.

PMID- 19103291
TI  - GTPase dependent recruitment of Grif-1 by Miro1 regulates mitochondrial
      trafficking in hippocampal neurons.
AB  - The transport of mitochondria to specific neuronal locations is critical to meet
      local cellular energy demands and for buffering intracellular calcium. A critical
      role for kinesin motor proteins in mitochondrial transport in neurons has been
      demonstrated. Currently however the molecular mechanisms that underlie the
      recruitment of motor proteins to mitochondria, and how this recruitment is
      regulated remain unclear. Here we show that a protein trafficking complex
      comprising the adaptor protein Grif-1 and the atypical GTPase Miro1 can be
      detected in mammalian brain where it is localised to neuronal mitochondria.
      Increasing Miro1 expression levels recruits Grif-1 to mitochondria. This results
      in an enhanced transport of mitochondria towards the distal ends of neuronal
      processes. Uncoupling Grif-1 recruitment to mitochondria by expressing a Grif
      1/Miro1 binding fragment dramatically reduces mitochondrial transport into
      neuronal processes. Altering Miro1 function by mutating its first GTPase domain
      affects Miro's ability to recruit Grif-1 to mitochondria and in addition alters
      mitochondrial distribution and shape along neuronal processes. These data suggest
      that Miro1 and the kinesin adaptor Grif-1 play an important role in regulating
      mitochondrial transport in neurons.

PMID- 19103293
TI  - Functional imaging studies of episodic memory in Alzheimer's disease: a
      quantitative meta-analysis.
AB  - Alzheimer's Disease (AD) is a progressive neurodegenerative disorder, rapidly
      increasing in prevalence as the population ages. As the potential for disease
      modifying therapy grows, a large body of literature has aimed at finding
      reliable, noninvasive biomarkers of AD, to allow for early intervention and
      sensitive tracking of therapeutic response. Task-related functional brain imaging
      techniques have been increasingly used to examine episodic memory function in AD.
      In the present study we completed a quantitative meta-analysis of this growing
      literature, to establish consensus and elucidate consistent patterns across this
      important research area. Results from encoding and retrieval paradigms were
      analyzed using the activation likelihood estimation (ALE) technique for patient
      and control groups. Second-level ALE analyses directly compared activation
      between these two groups. Results indicated a number of consistent findings
      across the included studies. Controls showed consistently greater activity than
      patients in a number of regions including the MTL and frontal pole across
      encoding and retrieval paradigms. Patients demonstrated increased activation
      likelihood in areas of the ventral lateral prefrontal cortex and other regions.
      Our findings quantitatively confirm the widely-cited deficits in MTL activity
      among AD patients, and also bring to light a pattern of differential prefrontal
      involvement, which may be implicated in compensatory changes occurring in AD. On
      the whole, this study quantitatively demonstrates that functional imaging studies
      show consistent, if complex, patterns of brain activation differences between
      patients and controls. These findings support the continued evaluation of
      functional neuroimaging for clinical use.

PMID- 19103292
TI  - Identification of neuronal target genes for CCAAT/enhancer binding proteins.
AB  - CCAAT/Enhancer Binding Proteins (C/EBPs) play pivotal roles in the development
      and plasticity of the nervous system. Identification of the physiological targets
      of C/EBPs (C/EBP target genes) should therefore provide insight into the
      underlying biology of these processes. We used unbiased genome-wide mapping to
      identify 115 C/EBPbeta target genes in PC12 cells that include transcription
      factors, neurotransmitter receptors, ion channels, protein kinases and synaptic
      vesicle proteins. C/EBPbeta binding sites were located primarily within introns,
      suggesting novel regulatory functions, and were associated with binding sites for
      other developmentally important transcription factors. Experiments using dominant
      negatives showed C/EBPbeta to repress transcription of a subset of target genes.
      Target genes in rat brain were subsequently found to preferentially bind
      C/EBPalpha, beta and delta. Analysis of the hippocampal transcriptome of
      C/EBPbeta knockout mice revealed dysregulation of a high percentage of
      transcripts identified as C/EBP target genes. These results support the
      hypothesis that C/EBPs play non-redundant roles in the brain.

PMID- 19103294
TI  - Lateralization of the serotonin-1A receptor distribution in language areas
      revealed by PET.
AB  - Lateralization is a well described aspect of the human brain. A plethora of
      morphological, cytological and functional studies describes hemispheric asymmetry
      in auditory and language areas. However, no study has reported cortical
      lateralization in the healthy human brain in vivo on the level of
      neurotransmitter receptors and in relation to functional organization so far. In
      this study, we assessed the distribution of the main inhibitory serotonergic
      receptor (the 5-HT1A receptor) and analyzed its regional binding with regard to
      hemisphere, sex and plasma levels of sex steroid hormones (testosterone,
      estradiol, progesterone). We quantified the 5-HT1A receptor binding potential by
      positron emission tomography (PET) using the highly selective and specific
      radioligand [carbonyl-11C]WAY-100635 and measured hormone levels in thirty-four
      (16 females, 18 males) healthy right-handed subjects. The obtained data were
      analyzed in an automated region of interest (ROI) based approach investigating 14
      auditory, language and limbic areas. We found significantly higher 5-HT1A
      receptor binding in the superior and middle frontal gyri of the right hemisphere,
      the triangular and orbital parts of the inferior frontal gyrus, the supramarginal
      gyrus, the superior gyrus of the temporal pole and the middle temporal gyrus.
      Regions of the primary and secondary auditory cortex (Heschl's gyrus and superior
      temporal gyrus) and the Rolandic operculum displayed significantly higher
      receptor binding in the left hemisphere. 5-HT1A receptor binding was 1.8-2.9%
      higher in right frontal ROIs and 2-3.6% higher in left primary and secondary
      auditory regions. There was no hemispheric difference in 5-HT(1A) receptor
      binding in the hippocampus, amygdala, and insula. Post-hoc testing suggested that
      lateralization of 5-HT1A receptor binding differed between the sexes in the
      triangular part of the inferior frontal gyrus. For the first time, this PET study
      shows lateralization of the main inhibitory receptor of the serotonergic system
      in functionally asymmetric organized regions of the healthy human brain in vivo.

PMID- 19103295
TI  - Computerized assessment of vessel morphological changes during treatment of
      glioblastoma multiforme: report of a case imaged serially by MRA over four years.
AB  - A patient with glioblastoma multiforme underwent serial computerized analysis of
      tumor-associated vasculature defined from magnetic resonance angiographic (MRA)
      scans obtained over almost a four year period. The clinical course included tumor
      resection with subsequent radiation therapy, a long symptom-free interval,
      emergence of a new malignant focus, resection of that focus, a stroke, and
      treatment with chemotherapy and anti-angiogenic therapy. Image analysis methods
      included segmentation of vessels from each MRA and statistical comparison of
      vessel morphology over 4 regions of interest (the initial tumor site, the second
      tumor site, a distant control region, and the entire brain) to the same 4 regions
      of interest in 50 healthy volunteers (26 females and 24 males; mean age 39
      years). Results suggested that following completion of focal radiation therapy
      (RT) vessel shape abnormalities, if elevated at the time of RT completion, may
      progressively normalize for months in focal regions, that progressively severe
      vessel shape abnormalities can precede the emergence of a gadolinium enhancing
      lesion by months, that lesion resection can produce a dramatic but highly
      transient drop in abnormal vessel tortuosity both focally and globally, and that
      treatment with anti-angiogenic agents does not necessarily normalize vessel
      shape. Quantitative measurements of vessel morphology as defined from MRA may
      provide useful insights into tumor development and response to therapy.

PMID- 19103296
TI  - Connectivity and signal intensity in the parieto-occipital cortex predicts top
      down attentional effect in visual masking: an fMRI study based on individual
      differences.
AB  - Top-down attention affects even the early stages of visual processing. For
      example, several studies have reported that instructions prior to the
      presentation of visual stimuli can both enhance and reduce visual masking. The
      finding that top-down processing influences perceptual processing is called the
      attentional effect. However, the magnitude of the attentional effect differs
      between individuals, and how these differences relate to brain activation remains
      to be explained. One possibility would be that activation intensity predicts the
      magnitude of the attentional effect. Another possible explanation would be that
      effective connectivity among activated areas determines the attentional effect.
      In the present study, we used structural equation modeling to analyze individual
      differences in the attentional effect on visual masking, in relation to the
      signal and connectivity strength of activated brain regions prior to presentation
      of the visual stimuli. The results showed that signal intensity was positively
      correlated with attentional effect in the occipital areas, but not in fronto
      parietal areas, and the effect was also positively correlated with connective
      efficiency from the right intraparietal sulcus (IPS) to the bilateral fusiform
      gyrus (GF). Furthermore, a higher degree of effective connections from the right
      IPS to the GF led to greater neural activity in the GF. We therefore propose that
      the effective modulator in the parietal areas and strong activation in the visual
      areas together and in cooperation predict higher attentional effects in visual
      processing.

PMID- 19103298
TI  - Effects of lactoferrin on the differentiation of pluripotent mesenchymal cells.
AB  - Lactoferrin accelerates bone formation, but the precise cellular mechanism behind
      this is still unclear. We examined the effect of lactoferrin on the
      differentiation of pluripotent mesenchymal cells using a typical pluripotent
      mesenchymal cell line, C2C12. Cells were cultured in low-mitogen differentiation
      medium to induce cell differentiation, with or without the addition of
      lactoferrin. The cell lineage was determined by alkaline phosphatase (ALPase)
      activity, mRNA expression of cellular phenotype-specific markers using real-time
      polymerase chain reaction (PCR), and protein synthesis using Western blotting.
      The expression of low-density lipoprotein lipase receptor-related proteins (LRPs)
      1 and 2, both lactoferrin receptors, was determined by reverse transcription-PCR.
      ALPase activity increased after the addition of lactoferrin. The mRNA expression
      of Runx2, osteocalcin, and Sox9 increased markedly as a result of lactoferrin
      treatment, whereas the expression of MyoD, desmin, and PPARgamma decreased
      significantly. Western blots showed that lactoferrin stimulation increased Runx2
      and Sox9 proteins, whereas it decreased MyoD and PPARgamma synthesis. C2C12 cells
      expressed the LRP1 lactoferrin receptor. These results indicate that lactoferrin
      treatment converts the differentiation pathway of C2C12 cells into the
      osteoblastic and chondroblastic lineage.

PMID- 19103297
TI  - The emerging discipline of Computational Functional Anatomy.
AB  - Computational Functional Anatomy (CFA) is the study of functional and
      physiological response variables in anatomical coordinates. For this we focus on
      two things: (i) the construction of bijections (via diffeomorphisms) between the
      coordinatized manifolds of human anatomy, and (ii) the transfer (group action and
      parallel transport) of functional information into anatomical atlases via these
      bijections. We review advances in the unification of the bijective comparison of
      anatomical submanifolds via point-sets including points, curves and surface
      triangulations as well as dense imagery. We examine the transfer via these
      bijections of functional response variables into anatomical coordinates via group
      action on scalars and matrices in DTI as well as parallel transport of metric
      information across multiple templates which preserves the inner product.

PMID- 19103299
TI  - Docetaxel/zoledronic acid combination triggers apoptosis synergistically through
      downregulating antiapoptotic Bcl-2 protein level in hormone-refractory prostate
      cancer cells.
AB  - Docetaxel, a semi-synthetic taxane analogue, is used effectively in the treatment
      of metastatic prostate cancer. Zoledronic acid, the most potent member of
      bisphosphonates, has shown pleiotropic anti-tumoral effects on prostate cancer
      cells. We have explored the possible additive/synergistic effects and the
      apoptotic pathways induced by combination treatment of docetaxel and zoledronic
      acid in hormone and drug refractory, PC-3 and DU-145 prostate cancer cells.
      Combination of docetaxel and zoledronic acid synergistically inhibits cell growth
      in PC-3 and DU-145 cells. Moreover, this effect was due to downregulation of
      antiapoptotic protein Bcl-2 in PC-3 and DU-145 cells. In conclusion,
      docetaxel/zoledronic acid combination is potentially a novel and effective
      approach for the treatment of prostate cancer.

PMID- 19103300
TI  - Characterization of dehydrodolichyl diphosphate synthase gene in rainbow trout
      (Oncorhynchus mykiss).
AB  - Dehydrodolichyl diphosphate synthase (DHDDS) catalyzes cis-prenyl chain
      elongation to produce the polyprenyl backbone of Dolichol, a glycosyl carrier
      lipid required for the co-translational modification of various proteins. The
      resulting glycoproteins play a role in several physiological and pathological
      processes. This manuscript characterizes the DHDDS-like gene from rainbow trout
      (Oncorhynchus mykiss) and its tissue-specific mRNA abundance in two different
      strains. The ubiquitous expression of DHDDS in trout indicates the essential
      function of the product Dolichol for metabolic processes. The comparison of the
      deduced amino acid sequence with DHDDS proteins from different vertebrate,
      invertebrate, and herbal species reveals a high degree of conserved amino acids
      and protein regions suggesting a common functional relevance. This is the first
      report of a prenyltransferase homologue from a teleostean species.

PMID- 19103301
TI  - Two different mechanisms for modulation of bronchoconstriction in guinea-pigs by
      cyclooxygenase metabolites.
AB  - Leukotriene D(4) (LTD(4))-induced bronchoconstriction in guinea-pig airways has a
      cyclooxygenase (COX)-dependent component. The main objective of this study was to
      establish if prostaglandin (PG) D(2)-induced bronchoconstriction also was
      modulated by COX products. The effects of non-selective and selective COX-1 and
      COX-2 inhibitors on bronchoconstriction induced by LTD(4) and PGD(2) were
      investigated in the perfused and ventilated guinea-pig lung (IPL). Both LTD(4)
      induced bronchoconstriction and thromboxane (TX) A(2) release was suppressed by
      COX inhibitors or by TX synthesis inhibition. The release of additional COX
      products following CysLT(1) receptor activation by LTD(4) was established by
      measurements of immunoreactive 6-keto PGF(1alpha) (a stable metabolite of PGI(2))
      and PGE(2). In contrast, TP receptor-mediated bronchoconstriction by PGD(2) was
      somewhat enhanced by COX inhibitors, and there was no measurable release of COX
      products after TP receptor activation with U-46619. PGE(2) was bronchoprotective
      in IPL as it inhibited the histamine-induced bronchoconstriction. In the isolated
      guinea-pig trachea, neither PGD(2) nor U-46619 actively released PGE(2), but
      continuous production of PGE(2) and PGI(2) was established, and the response to
      PGD(2) was enhanced also in the trachea by COX inhibition. The study documented
      that bronchoconstriction induced by LTD(4) and PGD(2) in IPL was modulated
      differently by COX products. Whereas bronchoconstriction induced by LTD(4) was
      amplified predominantly by secondarily released TXA(2), that induced by PGD(2)
      was attenuated by bronchoprotective PGE(2) and PGI(2), presumably tonically
      produced in the airways.

PMID- 19103302
TI  - Establishment of experimental conditions for preserving samples of fish blood for
      analysis with both comet assay and flow cytometry.
AB  - When environmental analysis is performed, the high number of samples required and
      handling conditions during the transport of these samples to the laboratory are
      common problems. The comet assay is a useful, highly sensitive tool in
      biomonitoring. Some studies in the literature aim to preserve slides in lysis
      solution for use in the comet assay. Until now, however, no efficient methodology
      for preserving blood samples for this assay has been described. Because of this,
      the present report aimed to establish the proper conditions for samples
      maintenance prior to comet assay analysis. Samples were conserved in three
      different solutions: a high protein concentration solution (fetal bovine serum
      FBS), an anticoagulant agent (a calcium chelator - ethylenediaminetetracetic acid
      - EDTA), and a salt buffered solution (phosphate buffered saline-PBS). Therefore,
      peripheral blood samples of Rhamdia quelen specimens were collected and
      maintained in these solutions until testing at 72h. Analyses of DNA fragmentation
      via the comet assay and cell viability via flow cytometry were performed at
      intervals of 24h. The results showed that samples maintained in FBS were
      preserved better; this was followed by those preserved in PBS and then last by
      those preserved in EDTA. In conclusion, blood samples from freshwater fish can be
      preserved up to 48h in fetal bovine serum at 4 degrees C in the absence of light.
      In this period, no DNA fragmentation occurs. We thus describe an excellent method
      of sample conservation for subsequent analysis in the laboratory.

PMID- 19103303
TI  - Mechanisms of clastogen-induced chromosomal aberrations: a critical review and
      description of a model based on failures of tethering of DNA strand ends to
      strand-breaking enzymes.
AB  - Most theories of the mechanisms of chromosomal aberrations involve the concepts
      of clastogens directly acting on DNA to produce strand breaks, and subsequently,
      the survival of these directly caused DNA strand breaks - or misrepairs of them -
      through to metaphase when they appear as chromosomal 'breaks' or translocations.
      Nevertheless, various observations are inconsistent with these theories such as
      the fact that many chemical clastogens (e.g. caffeine, acridines) do not
      covalently react with DNA, while almost all of the chemical clastogens (e.g.
      alkylating agents) which do react covalently with DNA, do not directly cause DNA
      strand breaks. This paper reviews the 'direct-clastogen damage to DNA' theories,
      and the phenomenology of chromosomal aberrations which are inconsistent with
      them. Then the theory is considered that the breaks in chromosomes seen at
      metaphase and anaphase are not the survivors of DNA breaks directly induced by
      clastogens, but rather derive from breaks created by the enzymes which repair
      damaged DNA. After that, newer knowledge is reviewed that (i) strand breaks are
      created during normal DNA unravelling (by topoisomerases), during DNA synthesis,
      and during DNA repairs, and these breaks can be single- or double-stranded, (ii)
      breaks variously associated with unravelling, synthesis and repair can occur
      'anywhere, anytime' (pre-synthesis, synthesis or post-synthesis) in the cell
      cycle, and (iii) the enzyme assemblies for DNA unravelling, synthesis and repair
      which make and religate the breaks must be non-covalently tethered to the ends of
      the DNA strands while the breaks created by the enzymes are in existence. It is
      then suggested that all the morphological types and other phenomena of
      chromosomal aberrations can be explained by aspects, mechanisms and effects of
      failures of this tethering function. Circumstances involving the basic mechanism
      (failure of DNA-end-tethering function while enzyme-created breaks are in
      existence) are described which might result in 'gaps', translocations
      ('exchanges'), complex lesions such as 'triradials', as well as in 'minutes',
      amplifications and inversions. Predictions are made concerning likely results in
      various suggested studies including those involving sensitive assays for DNA-end
      to-enzyme tethering functions in vitro.

PMID- 19103304
TI  - Chronic leptin treatment stimulates lipid oxidation in immortalized and primary
      mouse skeletal muscle cells.
AB  - Leptin administration enhances lipid oxidation in skeletal muscle. Nevertheless,
      direct and chronic effect of leptin has not been well characterized. Here, we
      measured the effect of leptin on skeletal muscles and their signaling pathways
      using differentiated C(2)C(12) myotubes and primary myotube cultures.
      Differentiated myotubes expressed both the short and long forms of leptin
      receptors. Leptin increased lipid oxidation in myotubes in a concentration- and
      time-dependent manner, with significant induction of lipid oxidation occurring
      after 6 h. Actinomycin D completely blocked leptin-induced lipid oxidation.
      Leptin significantly increased phosphorylation of JAK2 and STAT3 in myotubes, and
      leptin-induced lipid oxidation was abolished by treatment with a JAK2 inhibitor
      or STAT3 siRNA. We then used mouse myotubes to measure these effects under
      physiological conditions. Leptin increased lipid oxidation, which again was
      blocked by a JAK2 inhibitor and STAT3 siRNA. These results suggest that the
      JAK2/STAT3 signaling pathway may underlie the chronic effects of leptin on lipid
      oxidation in skeletal muscles.

PMID- 19103305
TI  - Subcellular fractionation of Cu exposed oysters, Crassostrea virginica, and Cu
      accumulation from a biologically incorporated Cu rich oyster diet in Fundulus
      heteroclitus in fresh and sea water.
AB  - In order to examine the effect of salinity on Cu accumulation from a naturally
      incorporated diet, oysters (Crassostrea virginica) were exposed in sea water for
      96 days to four waterborne [Cu]: 2.9+/-0.7 (control), 4.3+/-0.6, 5.4+/-0.5, and
      10.7+/-1.0 microg L(-1). After 96 days, the control whole body [Cu] increased
      from 2.1+/-0.5 to 9.1+/-1.1 microg g(-1) w.w. and the highest [Cu] was 163.4+/
      27.1 microg g(-1) w.w. in the oysters. Despite large differences in tissue [Cu],
      there was no effect on the fraction of trophically available metal in the oyster
      suggesting that trophic transfer will correlate well with tissue [Cu]. The
      control and highest [Cu] oysters became diet for killifish (Fundulus
      heteroclitus) in fresh and seawater for 40 days. The two diets contained 84.7+/
      5.1 and 850.5+/-8.8 microg Cu g(-1) d.w. Fish were fed a combined diet of oyster
      and a pellet supplement (20.5+/-1.0 microg Cu g(-1) d.w.) both at 5% body mass
      day(-1). In killifish, Cu increased approximately 7% in gills and 100% in
      intestines after 6 weeks of exposure to the high Cu diet. No other tissues
      accumulated Cu above control levels. An 11-fold difference free Cu(2+)
      concentrations was predicted in intestinal fluid between fresh and sea water, but
      there was no corresponding effect of salinity on intestinal Cu accumulation
      suggesting that Cu is not accumulated as the free ion.

PMID- 19103306
TI  - Characterization of hantaviruses circulating in Central Brazil.
AB  - In 2004, an outbreak of HCPS in Brazil made hantaviruses a national threat to the
      rural and urban population. During this outbreak, 164 cases were reported, and
      18.3% of them occurred in the Federal District. In this study, hantavirus genomic
      sequences were amplified from seven patients who resided in Central Brazil and
      then sequenced and compared to other hantavirus sequences. The complete S segment
      sequence, which is 1847 bases long and potentially encodes the 428 amino acid
      nucleocapsid protein, was determined for one patient. Moreover, a 700 base-pair
      sequence of the S segment was obtained from two other patients, and we analyzed M
      segment sequences from all samples. It can be inferred by both identity and
      phylogenetic analysis that the sequences obtained are highly related to
      Araraquara variant and Maciel virus. Phylogenetic results show that hantaviruses
      isolated in Central Brazil can be divided into two monophyletic groups: one group
      that clusters with Araraquara variant and the other group that includes the
      complete S segment sequence obtained in this study. Therefore, we propose the
      name Paranoa for this variant that co-exists with the Araraquara-like hantavirus
      in Central Brazil.

PMID- 19103307
TI  - A novel peptide isolated from phage display peptides library recognized by an
      antibody against connective tissue growth factor (CTGF).
AB  - The aim of this study was to isolate a peptide binding to an antibody against
      CTGF C-terminal domain from the peptide library and to evaluate its immunological
      and biological activities. A phage display 12-mer peptide library was screened
      using anti-CTGF/C antibody as the target. Ten of the positive clones were
      sequenced after three rounds bio-panning. The DNA encoding peptide ZD521 was
      cloned and expressed as the fusion protein(TrxA-ZD521). The specificity of ZD521
      to anti-CTGF/C antibody was determined by competitive inhibition assay. Mice were
      immunized with purified fusion protein(TrxA-ZD521) and the anti-peptide or anti
      CTGF response of antiserum was also tested by enzyme-linked immunoabsorbent assay
      (ELISA) and Western blot. The inhibition effect of anti-serum on proliferation of
      kidney mesangial cells was evaluated by MTT. A peptide ZD521(GEPQTKLFSFPL) that
      could specifically recognize anti-CTGF/C antibody was isolated. No sequence
      homology was found between ZD521 and CTGF/C. The purified TrxA-ZD521 could
      specifically bind to anti-CTGF/C antibody and block the binding of anti-CTGF/C
      antibody to CTGF/C and native CTGF(mesangial cell lysate). Moreover, the
      antiserum from mice immunized with TrxA-ZD521 could also bind to CTGF/C
      recombinant protein and native CTGF, as well as significantly inhibit the
      proliferation of kidney mesangial cells induced by CTGF/C. Therefore, ZD521 might
      be a conformational epitope of CTGF which is potentially useful to be developed
      as a vaccine for prevention and treatment of fibrosis disorders.

PMID- 19103308
TI  - Endothelial progenitor cell therapy in atherosclerosis: a double-edged sword?
AB  - Atherosclerosis, an inflammatory process that selectively affects arteries, is
      highly prevalent in human. Thrombo-occlusive complications of atherosclerosis,
      including stroke and myocardial infarction, are becoming major causes of
      morbidity and mortality in the industrialized world. Atherosclerosis develops in
      response to local endothelial injuries. Endothelial dysfunction and cell loss are
      prominent features in atherosclerosis. Restoring the endothelial lining to normal
      is critical for slowing or reversing the progression of atherosclerosis.
      Increasing data suggest that endothelial progenitor cells (EPCs) play a
      significant role in reendothelialization of the injured blood vessels. This
      review focuses on the effects of EPC mobilization and transfusion in the
      condition of atherosclerosis. The aim of the review is to provide an update on
      the progress in this research field, highlight the role of EPCs in
      atherosclerosis and discuss the possible mechanisms and potential risks of
      progenitor cell-based therapy in atherosclerosis.

PMID- 19103309
TI  - PM1-Alpha ELISA: the assay of choice for the detection of anti-PM/Scl
      autoantibodies?
AB  - A characteristic serological feature of patients suffering from the overlap
      polymyositis and scleroderma (PM/Scl) syndrome are antibodies to the human
      counterpart of the yeast exosome referred to as the PM/Scl complex. Historically,
      the detection of anti-PM/Scl antibodies was laborious and relied largely on
      indirect immunofluorescence and immunodiffusion techniques. In 1992 the major
      autoantigen PM/Scl-100 was identified and cloned. Subsequently, the major
      epitopes were mapped and one of these, termed PM1-Alpha, became the antigen for a
      novel ELISA exhibiting high sensitivity and specificity for the detection of anti
      PM/Scl antibodies. Comparative studies with other methods using other PM/Scl
      autoantigens have shown that the PM1-Alpha ELISA has higher sensitivity and
      specificity than assays that employed recombinant PM/Scl-75c and PM/Scl-100. Anti
      PM1-Alpha antibodies were identified in 55.0% of sera from PM/Scl overlap
      syndrome patients, but were also seen in 7.9% of SSc and in 7.5% of PM patients.
      The frequency in other systemic autoimmune diseases and in infectious diseases
      was significant lower. In summary, the data derived from individual studies
      suggest that PM1-Alpha may become the "gold standard" for the detection of anti
      PM/Scl antibodies.

PMID- 19103310
TI  - Bacterial multidrug transport through the lens of the major facilitator
      superfamily.
AB  - Multidrug transporters are membrane proteins that expel a wide spectrum of
      cytotoxic compounds from the cell. Through this function, they render cells
      resistant to multiple drugs. These transporters are found in many different
      families of transport proteins, of which the largest is the major facilitator
      superfamily. Multidrug transporters from this family are highly represented in
      bacteria and studies of them have provided important insight into the mechanism
      underlying multidrug transport. This review summarizes the work carried out on
      these interesting proteins and underscores the differences and similarities to
      other transport systems.

PMID- 19103311
TI  - Incorporation of 5-hydroxytryptophan into transferrin and its receptor allows
      assignment of the pH induced changes in intrinsic fluorescence when iron is
      released.
AB  - Human serum transferrin (hTF) is a bilobal glycoprotein that transports iron to
      cells. At neutral pH, diferric hTF binds with nM affinity to the transferrin
      receptor (TFR) on the cell surface. The complex is taken into the cell where, at
      the acidic pH of the endosome ( approximately pH 5.6), iron is released. Since
      iron coordination strongly quenches the intrinsic tryptophan fluorescence of hTF,
      the increase in the fluorescent signal reports the rate constant(s) of iron
      release. At pH 5.6, the TFR considerably enhances iron release from the C-lobe
      (with little effect on iron release from the N-lobe). The recombinant soluble TFR
      is a dimer with 11 tryptophan residues per monomer. In the hTF/TFR complex these
      residues could contribute to and compromise the readout ascribed to iron release
      from hTF. We report that compared to Fe(C) hTF alone, the increase in the
      fluorescent signal from the preformed complex of Fe(C) hTF and the TFR at pH 5.6
      is significantly quenched (75%). To dissect the contributions of hTF and the TFR
      to the change in fluorescence, 5-hydroxytryptophan was incorporated into each
      using our mammalian expression system. Selective excitation of the samples at 280
      or 315 nm shows that the TFR contributes little or nothing to the increase in
      fluorescence when ferric iron is released from Fe(C) hTF. Quantum yield
      determinations of TFR, Fe(C) hTF and the Fe(C) hTF/TFR complex strongly support
      our interpretation of the kinetic data.

PMID- 19103312
TI  - The modification of alpha-synuclein by dicarbonyl compounds inhibits its fibril
      forming process.
AB  - Oxidative modification of alpha-synuclein (alphaSyn) was reported to have
      significant effects on its amyloidogenic properties. Dicarbonyl compounds are
      metabolites accumulated by various oxidative processes in the intracellular
      environment. In this study, two dicarbonyl compounds, methylglyoxal (MGO) and
      glyoxal (GO), were investigated for their effects on the structural and fibril
      forming properties of alphaSyn. Both compounds were found to induce the
      oligomerization of alphaSyn. By adding substoichiometric amounts of alphaSyn
      modified by MGO or GO, the fibrillization of alphaSyn was substantially
      inhibited. The heterogeneously-modified alphaSyns were separated into three
      fractions: monomers, oligomers, and high molecular mass oligomers. When each
      modified alphaSyn species was used to seed fibril formation, protein
      fibrillization was significantly suppressed. Temperature scanning and
      interactions with liposomes revealed that both MGO- and GO-modified monomers were
      not as susceptible as the unmodified alphaSyn to conformational changes into
      partially folded intermediates and alpha-helixes. Our observations suggest that
      dicarbonyl modification of alphaSyn reduces conformational flexibility of the
      protein, thereby contributing to a reduction in the ability of alphaSyn to form
      fibrils, and the modified protein inhibits the fibrillization of the unmodified
      alphaSyn.

PMID- 19103313
TI  - Proteomic analysis of human macrophages exposed to hypochlorite-oxidized low
      density lipoprotein.
AB  - The invasion of monocytes through the endothelial wall of arteries and their
      transformation from macrophage into form cells has been implicated as a critical
      initiating event in atherogenesis. Human THP-1 monocytic cells can be induced to
      differentiate into macrophages by phorbol myristate acetate (PMA) treatment, and
      can be converted into foam cells by exposure to oxidized low-density lipoprotein
      (oxLDL). To identify proteins potentially involved in atherosclerotic processes,
      we performed a proteomic analysis of THP-1 macrophages exposed to oxLDL generated
      by treatment with native LDL with hypochlorous acid/hypochlorite (HOCl/OCl(-)).
      We detected more than a thousand proteins, of which 104 differentially expressed
      proteins were identified by matrix-assisted laser desorption/ionization time-of
      flight mass spectrometry (MALDI-TOF) and the NCBI database. The largest
      differences in expression were observed for bifunctional purine biosynthesis
      protein, vacuolar protein sorting 33A, breast carcinoma amplified sequence,
      adenine phosphoribosyltransferase, and tropomyosin alpha 3 chain. Interestingly,
      many apoptotic proteins such as lamin B1, poly (ADP-ribose) polymerase, Bcl-2
      related protein A1 and vimentin were identified by MALDI-TOF analysis. Identities
      were confirmed by matching the sequence of several tryptic peptides using MALDI
      TOF/TOF MS, Western blot analyses and immunofluorescent microscopy. The data
      described here will contribute to establishing a functional profile of the human
      macrophage proteome. Furthermore, the proteins identified in this study are
      attractive candidates for further biomarkers involved in the pathogenesis of
      atherosclerosis.

PMID- 19103314
TI  - Tracking of bone mass from childhood to adolescence and factors that predict
      deviation from tracking.
AB  - It has been hypothesized that bone density tracks but long term studies in
      children are lacking. As such, the aim of this study was to describe tracking of
      dual X-ray absorptiometry measures from age 8 to age 16 years, whether this was
      independent of change in body size and whether deviation from tracking could be
      predicted. 116 males and 67 females had anthropometric (height and weight),
      questionnaire (medication use, sports, breastfeeding), fitness (PWC(170)) and DXA
      measures (bone free lean mass [LM], fat mass [FM] and bone mass) at baseline and
      follow-up. BMC and aBMD were assessed at the spine and hip and total body and
      bone mineral apparent density (BMAD) at the spine and hip. We found all DXA
      measures tracked significantly after adjustment for change in height and change
      in weight (males: R(2): BMC 24-62%; aBMD 41-48%; BMAD 30-37%, females: R(2): BMC
      45-72%; aBMD 36-56%; BMAD 30-48%). Factors that predicted subjects would deviate
      positively, that is improve in tertile or remain in the highest tertile of spine
      and hip aBMD included having been breastfed, increase in LM, PWC(170) at age 8
      and sport participation in males. LM at age 8 was beneficial in males while in
      females; FM at age 8 predicted subjects would deviate positively. Boys who gained
      absolute and percent FM and girls who gained percent FM, were more likely to
      deviate negatively, that is, decrease in tertile or remain in the lowest tertile
      of spine and hip aBMD. ICS use at age 8 also predicted subjects, particularly
      males would not improve in bone mass relative to their peers. In conclusion, DXA
      measures track moderately to strongly from childhood to adolescence. This was
      independent of linear growth and sex indicating bone development and physical
      growth are under largely separate mechanistic control. Body composition was the
      main predictor of altered tracking but environmental factors also appear
      important.

PMID- 19103316
TI  - Make time for daily physical activity.

PMID- 19103317
TI  - Positive attitude goes a long way--in dietetics and in life.

PMID- 19103318
TI  - Person-first practice: treating patients with disabilities.

PMID- 19103319
TI  - Marketing yourself and taking risks.

PMID- 19103320
TI  - The need for time-intensive information in healthful eating and physical activity
      research: a timely topic.

PMID- 19103321
TI  - Fourth graders' reports of fruit and vegetable intake at school lunch: does
      treatment assignment affect accuracy?
AB  - OBJECTIVE: Dietary interventions with children often use self-reported data to
      assess efficacy despite that objective methods rarely support self-report
      findings in validation studies. This study compared fourth graders' self-reported
      to observed lunch fruit and vegetable intake to determine if the accuracy of self
      reported intake varied by treatment condition. DESIGN: Matched randomized follow
      up design examined three treatment groups (high and low intensity interventions
      and control) post-intervention. SUBJECTS/SETTING: Three hundred seventy-nine
      middle-school children participating in a randomized controlled trial of a school
      based fruit and vegetable intervention were observed during school lunch one day
      and asked to recall intake the following day. MAIN OUTCOME MEASURES: Food items
      were coded as: "match," "omission," or "intrusion." Students were classified as
      accurate if all food items matched, otherwise inaccurate. Matched foods' portions
      were compared for accuracy. Servings were computed for total fruit and vegetable
      intake. ANALYSES: Accuracy for fruits and vegetables were compared in separate
      analyses and tested for multiple potential associates: treatment condition, sex,
      race, body mass index, subsidized meal eligibility, school district,
      fruit/vegetable availability, age, and test scores. Fitted multivariable
      regression models included variables found to be significant in univariate or
      chi(2) analyses. RESULTS: Variables found to be significant for fruit item
      accuracy were availability at lunch, body mass index, and subsidized lunch
      eligibility. For vegetable item accuracy, availability at lunch was significant.
      No differences were found for food portions or for efficacy of the intervention
      between the two methods of dietary data collection: observation and self-report.
      CONCLUSIONS: Condition assignment did not bias recalled fruit and vegetable
      intakes among fourth graders.

PMID- 19103322
TI  - Seasonal variation in fruit and vegetable consumption in a rural agricultural
      community.
AB  - BACKGROUND: Seasonal variation in fruit and vegetable consumption has been
      documented in a limited number of previous investigations and is important for
      the design of epidemiologic investigations and in the evaluation of intervention
      programs. OBJECTIVE: This study investigates fruit and vegetable consumption
      behaviors among Hispanic farmworkers and non-farmworkers in a rural agricultural
      community. DESIGN: A larger study recruited 101 farmworker families and 100 non
      farmworker families from the Yakima Valley in Washington State between December
      2004 and October 2005. All families were Hispanic. An in-person administered
      questionnaire collected information on consumption of locally grown fruits and
      vegetables and sources of obtaining fruits and vegetables. Data on dietary intake
      asked whether or not the respondent had consumed a given fruit or vegetable in
      the past month. Data were collected longitudinally, coinciding with three
      agricultural seasons: thinning (summer), harvest (fall), and nonspray (winter).
      STATISTICAL ANALYSES PERFORMED: Generalized estimating equations were used to
      test for statistical significance between proportions of the population who
      consumed a given fruit or vegetable across agricultural seasons. Multivariable
      logistic regression was performed and corresponding odds ratios and 95%
      confidence intervals are reported. RESULTS: The proportion of respondents who ate
      apples, pears, plums, peaches, apricots, peppers, corn, and cucumbers was highest
      in the fall harvest season, whereas the proportions of those who ate cherries and
      asparagus were highest in the summer thinning season. Compared to non
      farmworkers, a higher proportion of farmworkers reported having eaten peaches,
      apricots, cherries, green beans, carrots, peppers, corn, pumpkin, squash, and
      onions, in the past month. CONCLUSIONS: Epidemiologic investigations and public
      health interventions that examine the consumption of fruits and vegetables should
      consider seasonal variation in consumption patterns, especially in agricultural
      communities.

PMID- 19103323
TI  - Resemblance in dietary intakes between urban low-income African-American
      adolescents and their mothers: the healthy eating and active lifestyles from
      school to home for kids study.
AB  - OBJECTIVES: To examine the association and predictors of dietary intake
      resemblance between urban low-income African-American adolescents and their
      mothers. METHODS: Detailed dietary data collected from 121 child-parent pairs in
      Chicago during fall 2003 were used. The association was assessed using
      correlation coefficients, kappa, and percentage of agreement, as well as logistic
      regression models. RESULTS: Overall, the association was weak as indicated by
      correlations and other measures. None of the mother-son correlations for
      nutrients and food groups were greater than 0.20. Mother-daughter pairs had
      stronger correlations (0.26 for energy and 0.30 for fat). The association was
      stronger in normal-weight mothers than in mothers with overweight or obesity.
      Logistic models showed that mother being a current smoker, giving child more
      pocket money, and allowing child to eat or purchase snacks without parental
      permission or presence predicted a higher probability of resemblance in
      undesirable eating patterns, such as high-energy, high-fat, and high-snack
      intakes (P<0.05). CONCLUSIONS: Mother-child diet association was generally weak,
      and varied considerably across groups and intake variables in this homogenous
      population. Some maternal characteristics seem to affect the association.

PMID- 19103324
TI  - Total antioxidant content of alternatives to refined sugar.
AB  - BACKGROUND: Oxidative damage is implicated in the etiology of cancer,
      cardiovascular disease, and other degenerative disorders. Recent nutritional
      research has focused on the antioxidant potential of foods, while current dietary
      recommendations are to increase the intake of antioxidant-rich foods rather than
      supplement specific nutrients. Many alternatives to refined sugar are available,
      including raw cane sugar, plant saps/syrups (eg, maple syrup, agave nectar),
      molasses, honey, and fruit sugars (eg, date sugar). Unrefined sweeteners were
      hypothesized to contain higher levels of antioxidants, similar to the contrast
      between whole and refined grain products. OBJECTIVE: To compare the total
      antioxidant content of natural sweeteners as alternatives to refined sugar.
      DESIGN: The ferric-reducing ability of plasma (FRAP) assay was used to estimate
      total antioxidant capacity. Major brands of 12 types of sweeteners as well as
      refined white sugar and corn syrup were sampled from retail outlets in the United
      States. RESULTS: Substantial differences in total antioxidant content of
      different sweeteners were found. Refined sugar, corn syrup, and agave nectar
      contained minimal antioxidant activity (<0.01 mmol FRAP/100 g); raw cane sugar
      had a higher FRAP (0.1 mmol/100 g). Dark and blackstrap molasses had the highest
      FRAP (4.6 to 4.9 mmol/100 g), while maple syrup, brown sugar, and honey showed
      intermediate antioxidant capacity (0.2 to 0.7 mmol FRAP/100 g). Based on an
      average intake of 130 g/day refined sugars and the antioxidant activity measured
      in typical diets, substituting alternative sweeteners could increase antioxidant
      intake an average of 2.6 mmol/day, similar to the amount found in a serving of
      berries or nuts. CONCLUSION: Many readily available alternatives to refined sugar
      offer the potential benefit of antioxidant activity.

PMID- 19103325
TI  - Making time for meals: meal structure and associations with dietary intake in
      young adults.
AB  - BACKGROUND: Prior studies have found that family meals and other aspects of meal
      structure are associated with dietary intake during adolescence, but little
      research has characterized meals in young adulthood. OBJECTIVE: This study was
      designed to describe attitudes regarding the social nature of meals, time
      constraints on meals, and meal regularity in young adults. In addition, this
      study aimed to describe the sociodemographic characteristics of young adults who
      report eating dinner with others and "eating on the run," and examine
      associations of these behaviors with meal attitudes and dietary intake. DESIGN:
      Data for this cross-sectional analysis were drawn from Project EAT (Eating Among
      Teens)-II, the second wave of a Minnesota population-based study.
      SUBJECTS/SETTING: Mailed surveys and food frequency questionnaires were completed
      in 2003-2004 by 1,687 young adult (mean age=20.5 years; 44% male) participants.
      MAIN OUTCOMES MEASURED AND STATISTICAL ANALYSES PERFORMED: chi(2) tests were
      calculated to examine differences in meal attitudes and behaviors according to
      sociodemographic characteristics. Relationships between meal attitudes and
      behaviors were explored using Spearman's correlation coefficients. Linear
      regression models adjusted for demographic characteristics were used to examine
      associations between meal behaviors and dietary intake variables. RESULTS: The
      majority of young adults reported they enjoy and value eating with others, but
      35% of males and 42% of females reported lacking time to sit down and eat a meal.
      Eating dinner with others was significantly associated (P</=0.01) with several
      markers of better dietary intake, including higher intakes of fruit, vegetables,
      and dark-green and orange vegetables. Eating on the run was significantly
      associated (P<0.01) with higher intakes of soft drinks, fast food, total fat and
      saturated fat, and lower intake of several healthful foods. CONCLUSIONS: Findings
      suggest that health services and programs for young adults should encourage
      taking the time to sit down for meals and to share meals with others.

PMID- 19103326
TI  - An introduction to qualitative research for food and nutrition professionals.
AB  - The purpose of this article is to define qualitative research, explain its
      design, explore its congruence with quantitative research, and provide examples
      of its applications in dietetics. Also, methods to ensure validity, reliability,
      and relevance are addressed. Readers will gain increased knowledge about
      qualitative research and greater competency in evaluating this type of research.
      The hope is that food and nutrition professionals will be inspired to conduct and
      publish qualitative research, adding to the body of peer-reviewed dietetics
      related qualitative publications. This type of research must be methodically
      planned and implemented with attention to validity, reliability, and relevance.
      This rigorous approach boosts the probability that the research will add to the
      scientific literature and qualify for publication.

PMID- 19103327
TI  - Motivational interviewing as a component of a school-based obesity prevention
      program for adolescent girls.
AB  - Over the past decade, motivational interviewing has been used by health
      professionals to promote health behavior changes and help individuals increase
      their motivation or "readiness" to change. This paper describes a preliminary
      study that evaluated the feasibility of motivational interviewing as a component
      of New Moves, a school-based obesity prevention program. New Moves is a program
      for inactive adolescent high school girls who are overweight or at risk of
      becoming overweight due to low levels of physical activity. Throughout the 18
      week pilot study, 41 girls, age 16 to 18 years, participated in an all-girls
      physical education class that focused on increasing physical activity, healthful
      eating, and social support. Individual sessions, using motivational interviewing
      techniques, were also conducted with 20 of the girls to develop goals and actions
      related to eating and physical activity. Among the 20 girls, 81% completed all
      seven of the individual sessions, and girls set a goal 100% of the time.
      Motivational interviewing offers a promising component of school-based obesity
      prevention programs and was found to be feasible to implement in school settings
      and acceptable to the adolescents.

PMID- 19103328
TI  - Effects of federal legislation on wellness policy formation in school districts
      in the United States.
AB  - The Reauthorization Act of 2004 required local education agencies sponsoring
      school meal programs to establish a wellness policy by the beginning of school
      year 2006-2007. The purpose of this study was to examine the process and outcome
      of wellness policy development in school districts. Phase 1 examined states'
      school nutrition legislation. Phase 2 consisted of qualitative interviews with
      foodservice directors. Phase 3 utilized an e-mail and mail survey. The sampling
      frame was a stratified random sample selected from medium-sized or larger schools
      (n=847). Factor analysis was conducted with Cronbach's alpha. Correlations tested
      relationships among variables using analysis of variance with Tukey's post hoc
      test. Before the federal mandate, few wellness components (37.4%) were in place
      for foodservice outside of the federally regulated meal program. Following the
      legislation, 72.4% of the wellness components were in place. Nutrition components
      were the variables that changed the most and were reported as the components most
      frequently implemented. Changes particularly noted in foodservice operations were
      the use of nutrition guidelines for a la carte foods, beverages, fundraisers,
      parties, and vending. Foodservice directors noted improvements in nutrition
      education and physical education. Foodservice directors reported less progress in
      the implementation and monitoring of the wellness policy than in the development
      of the policy. The top barriers to wellness policy development and implementation
      were the need to use food in fundraising and competition for time.

PMID- 19103329
TI  - Motivators and barriers to prenatal supplement use among minority women in the
      United States.
AB  - Minority women in the United States are at a higher risk of iron deficiency and
      less likely to report use of prenatal supplements compared with non-Hispanic
      white women. Little information exists on the perceived benefits and barriers to
      prenatal supplement use. We analyzed the results of 12 focus groups conducted
      with African-American and Hispanic women (n=104). Groups were equally divided
      into consistent (five to seven times per week for 3 or more months) and
      inconsistent (zero to four times per week for 0 to 2 months) users and by
      race/ethnicity. We examined motivators and barriers to prenatal supplement use
      and identified common themes; we also compared responses between consistent and
      inconsistent users, and between African American and Hispanic women. For all
      groups, positive effects, convenient supply, affordability, and reinforcement by
      health care providers enhanced adherence. Common barriers were prenatal
      supplement qualities, adverse effects, and poor communication from health care
      providers about the benefits of use. Common motivators among consistent users
      included social network reinforcement of daily intake and fear of adverse effects
      to the fetus if prenatal supplements were not taken. Common barriers among
      inconsistent users included skepticism toward the efficacy and necessity of
      prenatal supplements and the health care provider assenting to nonadherence.
      Prenatal supplement use was influenced by multiple factors in women's daily
      lives. Adherence will likely be enhanced by reducing barriers related to prenatal
      supplement qualities and adverse effects, improving social network support, and
      improving health care provider interactions.

PMID- 19103330
TI  - Menus in child care: a comparison of state regulations with national standards.
AB  - The purpose of this project was to compare individual state regulations regarding
      menus for child-care centers and family child-care homes with national menu
      standards. For all 50 states and the District of Columbia, state regulations were
      compared with menu standards found in Caring for Our Children--National Health
      and Safety Performance Standards: Guidelines for Out-of-Home Child Care Programs.
      Specifically, these guidelines suggest that (a) menus must be posted or made
      available to parents, (b) menus must be dated, (c) menus must reflect food
      served, (d) menus must be planned in advance, and (e) menus must be kept on file.
      One additional standard, that menus in child care are reviewed by a nutrition
      professional, was added to this review. Data were collected between June and
      August of 2007. Substantial variation existed among state regulations regarding
      menus. For child-care centers, seven states (14%) included regulations on all
      five standards, and 13 states (25%) had regulations on four of the five menu
      standards. Ten states (20%) did not have any regulations on the five menu
      standards. For family child-care homes, only three states (6%) had regulations on
      all five menu standards; four states (8%) had regulations on four of the five
      menu standards. Twenty-seven states (53%) did not have any regulations on the
      five standards for menus. Within the same state, regulations for child-care
      centers and family child-care homes often did not match. Overall, great
      discrepancies were found between model child-care menu policies and current state
      regulations in most states. States have the opportunity to improve regulations
      regarding menus to ensure that child-care providers develop accurate, specific,
      and healthful menus.

PMID- 19103331
TI  - Participants' comments on changes in the revised special supplemental nutrition
      program for women, infants, and children food packages: the Maryland food
      preference study.
AB  - The Institute of Medicine recommended changes in the Special Supplemental
      Nutrition Program for Women, Infants, and Children (WIC) food packages to help
      families from diverse populations establish more healthful dietary patterns. A
      cross-sectional study conducted during summer 2007 included interviews and focus
      groups with 223 WIC participants throughout Maryland. The objectives were to
      examine participants' responses to food package changes, to identify
      racial/ethnic differences, and to assess costs. All participants (100%) consumed
      fruits and vegetables. They preferred fresh for taste, but many endorsed canned
      and frozen for convenience and cost. Most women (56%) and children (69%) consumed
      whole milk and did not want reduced-fat milk. Few participants (13%) consumed soy
      products and most were uninterested in future consumption. Participants endorsed
      whole-wheat bread as more healthful and reported that they (59%) and their
      children (51%) would increase consumption if provided by WIC. Non-Hispanic
      participants preferred peanut butter over beans, Hispanic participants reported
      that they (44%) and their children (57%) would consume more beans (substituting
      for peanut butter) if provided by WIC. There were few differences in preferences
      between African-American and white participants. Hispanics differed from non
      Hispanics in preference for beans and dislike of frozen and canned vegetables,
      suggesting the importance of choices. The proposed food packages were cost
      neutral, except when extensive substitutions with soy products were allowed. By
      providing fruits and vegetables, reduced-fat options, and increased opportunities
      for nutrition education, the revised food packages may reduce the risk of obesity
      among low-income women, infants, and children.

PMID- 19103332
TI  - Effect of portion size information on food intake.
AB  - The term portion size is used differently by food manufacturers, regulatory
      agencies, and consumers. As such, it is unclear how information about portion
      size may influence perceived satiety and intake of foods by consumers. The
      objective of this study was to examine how portion size information influences
      satiety and intake, and how consumers interpret the term portion size. A
      randomized controlled design was used in which subjects were served a lunch meal
      consisting of a preload of pasta followed by ad libitum servings of the same
      pasta. In each of three separate sessions the subjects were told that the preload
      meal constituted 1/2, 1, or 1 1/2 portions of pasta. Thirty-three normal-weight
      subjects (22 males and 11 females) were recruited from a 250-member volunteer
      employee panel at Natick Research, Development, and Engineering Center during
      January 2005. Main measures were pre- and post-preload hunger/fullness ratings,
      liking ratings, amount consumed of the pasta after the preload, and Likert
      ratings of statements about different definitions of portion size. Results showed
      that portion size information did not influence satiety ratings or total intake.
      Consumers associated portion size more with daily nutrient requirements than with
      an ideal quantity for a satiating meal (P<0.01). Information about portion size
      may not be a good tool to manipulate food-intake behavior. Consumers' concept of
      portion size is associated more with objective measures of food than with
      personal experience about the amount that would be appropriate to eat.

PMID- 19103333
TI  - Assessing validity and reliability of resting metabolic rate in six gas analysis
      systems.
AB  - The Deltatrac Metabolic Monitor (DTC) (VIASYS Healthcare Inc, SensorMedics, Yorba
      Linda, CA), one of the most popular indirect calorimetry systems for measuring
      resting metabolic rate (RMR) in human subjects, is no longer being manufactured.
      This study compared five different gas analysis systems to the DTC. RMR was
      measured by the DTC and at least one other instrument at three study sites for a
      total of 38 participants. The five indirect calorimetry systems included the
      MedGraphics CPX Ultima (Medical Graphics Corp, St Paul, MN), the MedGem
      (Microlife USA, Golden, CO), Vmax Encore 29 System (VIASYS Healthcare Inc, Yorba
      Linda, CA), the TrueOne 2400 (Parvo Medics, Sandy, UT), and the Korr ReeVue (Korr
      Medical Technologies, Salt Lake City, UT). Validity was assessed using paired t
      tests to compare means; reliability was assessed by using both paired t tests and
      root mean square calculations with F tests for significance. Within-subject
      comparisons for validity of RMR revealed a significant difference between the DTC
      and the Ultima system. Bland-Altman plot analysis showed significant bias with
      increasing RMR values for the Korr and MedGem systems. Respiratory exchange ratio
      (RER) analysis showed a significant difference between the DTC and the Ultima
      system and a trend for a difference with the Vmax system (P=0.09). Reliability
      assessment for RMR revealed that all instruments had a significantly larger
      coefficient of variation (CV) (ranging from 4.8% to 10.9%) for RMR compared to
      the 3.0% CV for the DTC. Reliability assessment for RER data showed none of the
      instrument CVs was significantly larger than the DTC CV. The results were quite
      disappointing because none of the instruments equaled the within-person
      reliability of the DTC. The TrueOne and Vmax systems were the most valid
      instruments in comparison with the DTC for both RMR and RER assessment. Further
      testing is needed to identify an instrument with the reliability and validity of
      the DTC.

PMID- 19103334
TI  - Peer modeling influences girls' snack intake.
AB  - Previous studies indicate that the presence of peers influences children's food
      consumption. It is assumed that one factor producing this effect in children is
      child modeling of food intake. The present study assesses the effect of a video
      model on the food intake of overweight (n=22) and nonoverweight (n=22)
      preadolescent girls. A 2 (weight status)x2 (small vs large serving size)
      factorial design was used to test the hypothesis that youth model others' food
      intake. Serving sizes were manipulated by showing a video model selecting and
      consuming either a small or a large serving of cookies. Results indicate a main
      effect of serving size condition, F(1,40)=5.1, P<0.05 (d=0.65; 95% confidence
      interval: 0.35 to 0.65), and a main effect of weight status, F(1,40)=4.9, P<0.05
      (d=0.63; 95% confidence interval: 0.35 to 0.65). Participants exposed to the
      large serving-size condition consumed more cookies than participants exposed to
      the small serving-size condition and overweight participants consumed
      considerably more cookies than nonoverweight participants. The interaction of
      weight status by serving-size condition did not reach statistical significance
      (P=0.2). These results suggest that peer-modeling influences overweight and
      nonoverweight preadolescent girls' snack consumption.

PMID- 19103335
TI  - Macronutrient analysis of a nationwide sample of donor breast milk.
AB  - Banked donor milk may be a reasonable substitute for mother's milk for human
      infants. No data on the macronutrient composition of banked donor milk have been
      reported. This study determined the composition of donated milk from a large
      number of banked donor milk samples and compared it to the reported values for
      macronutrients in mature breast milk. During a 9-month sampling period (May 2006
      through February 2007) from a nationwide milk bank network, 415 sequential
      samples from 273 unique donors were analyzed for fat, protein, and lactose
      content, as well as energy density. Descriptive statistics were computed,
      including mean, standard deviation, coefficient of variation, median, and range.
      Percentiles were determined from the empirical distribution of the data. A ninety
      five percent confidence interval was computed using standard, large sample
      (Gaussian) methods. Banked donor milk mean values (in weight/volume) were found
      to be 1.16%+/-0.25% for protein, 3.22%+/-1.00% for fat, 7.80%+/-0.88% for
      lactose, and mean total energy was 65+/-11 kcal/dL. Banked donor milk
      macronutrient content was found to differ from the values reported in the
      literature for mature human milk. Unformulated banked donor milk alone, similar
      to mother's milk alone, does not have sufficient macronutrient content or energy
      density to sustain a very-low-birth-weight preterm infant. Fortification could
      make up for these shortcomings, perhaps making formulated banked donor milk a
      better choice for preterm infants than bovine-based formulas when mother's milk
      is unavailable.

PMID- 19103336
TI  - Do sack lunches provided by parents meet the nutritional needs of young children
      who attend child care?
AB  - Recent changes in Texas state regulations of child-care foodservice have resulted
      in more centers halting meal and snack preparation and requiring parents to
      provide food from home for their children. In the spring of 2006, sack lunches
      prepared at home for children attending licensed child-care centers were
      evaluated based on Dietary Reference Intakes (DRIs) and Child and Adult Care Food
      Program (CACFP) standards. The study included 3- to 5-year-old children attending
      full-time child-care centers that required parents to provide lunches. Lunch
      contents were observed and recorded for 3 consecutive days. A 3-day mean nutrient
      content was used to determine whether the lunches provided a minimum of 33% of
      the DRI. The following nutrients were evaluated: energy, carbohydrates, protein,
      dietary fiber, thiamin, riboflavin, niacin, vitamin C, vitamin A, calcium, iron,
      zinc, and sodium. Food items were summarized and compared with CACFP standards.
      More than 50% of the 3-day means provided less than 33% of the DRIs for energy
      (n=58), carbohydrate (n=59), vitamin A (n=58), calcium (n=49), iron (n=44), and
      zinc (n=38). Seventy-one of the 74 children (96%) received less than 33% of the
      DRI for dietary fiber, yet the mean amount of sodium in observed lunches was 114%
      of the DRI. The observed lunches did not meet the CACFP standards for servings of
      fruits and vegetables for 157 (71%) or for servings of milk in 178 (80%). Sack
      lunches sent from home may not regularly provide adequate nutrients for the
      growth and development of young children. Nutrition education should be provided
      to parents to ensure that sack lunches sent from home meet children's nutritional
      needs.

PMID- 19103337
TI  - Diet and physical activity patterns of school-aged children.
AB  - Childhood provides an opportunity for establishing healthful lifestyle habits,
      yet little is known about diet and physical activity patterns of elementary
      school-aged children. A cohort of 35 boys and girls in grades 3 through 5 (mean
      age=9.5 years) was studied during the course of the 2004-2005 school year,
      providing seasonal assessments of diet and physical activity. Objectively
      measured data included height, weight, and pedometer step counts. Subjective data
      included seasonal 3-day diet diaries, a food frequency questionnaire, and a
      physical activity questionnaire. Participants were white, well-nourished, and
      within the healthy range for body mass index for age. Only three students (9%)
      were overweight and another three were "at risk" for overweight. Food intake
      patterns fell far below MyPyramid guidelines for average daily servings of fruits
      and vegetables. High intakes of saturated fat (average of 12% of calories) and
      sodium were noted, along with inadequate fiber intakes. Snacks, desserts, and
      entrees that contributed most to calorie and saturated fat intake were
      identified. Self-reported physical activity appears in line with recommendations,
      but step counts fall short, particularly for girls and during winter months.
      These findings identify targets for behavioral and environmental interventions to
      reduce childhood obesity risks. Additional research involving more diverse
      populations is warranted.

PMID- 19103338
TI  - What is social networking? And how do I get clued in to LinkedIn?

PMID- 19103339
TI  - Radiological features of Meckel's diverticulum and its complications.
AB  - Meckel's diverticulum is the most common congenital abnormality of the small
      bowel. The majority of patients with this anomaly will remain asymptomatic;
      however, several complications may occur, including obstruction, intussusception,
      perforation, diverticulitis, and gastrointestinal haemorrhage. These
      complications may produce a variety of different clinical features and
      radiological appearances. The purpose of this article is to review the potential
      imaging manifestations of Meckel's diverticulum and its complications and discuss
      the advantages and disadvantages of the imaging techniques available.

PMID- 19103340
TI  - Ergonomics in radiology.
AB  - The use of computers is increasing in every field of medicine, especially
      radiology. Filmless radiology departments, speech recognition software,
      electronic request forms and teleradiology are some of the recent developments
      that have substantially increased the amount of time a radiologist spends in
      front of a computer monitor. Computers are also needed for searching literature
      on the internet, communicating via e-mails, and preparing for lectures and
      presentations. It is well known that regular computer users can suffer
      musculoskeletal injuries due to repetitive stress. The role of ergonomics in
      radiology is to ensure that working conditions are optimized in order to avoid
      injury and fatigue. Adequate workplace ergonomics can go a long way in increasing
      productivity, efficiency, and job satisfaction. We review the current literature
      pertaining to the role of ergonomics in modern-day radiology especially with the
      development of picture archiving and communication systems (PACS) workstations.

PMID- 19103341
TI  - Usefulness of concurrent reading using thin-section and thick-section CT images
      in subcentimetre solitary pulmonary nodules.
AB  - AIM: To evaluate the differences in the characterization and recommendation for
      follow-up of subcentimetre solitary pulmonary nodules (SSPNs) between 5 and 1mm
      section CT, and to compare the assessments generated by four radiologists
      MATERIALS AND METHODS: Five hundred and twenty-nine patients who had SSPNs on
      chest CT reconstructed using both 5 and 1mm sections were enrolled. Two image
      subsets of 5 and 1mm CT images of each nodule were interpreted independently by
      four radiologists. Nodule size, consistency (solid, partly solid, non-solid), the
      presence of calcification, and recommendations for follow-up were evaluated. If a
      non-calcified solid nodule was confirmed using CT, recommendation for follow-up
      was based on Fleischner Society guidelines. Data assessed by each radiologist
      were compared, and interobserver agreements were determined using the intraclass
      correlation coefficients and kappa value. RESULTS: Using 1mm CT images, the
      nodule sizes were significantly larger than on 5mm CT images (paired t-test,
      p<0.01). The presence of calcification and nodule consistency were significantly
      different between 5 and 1mm CT images (McNemar test for the presence of
      calcification, p<0.01; Wilcoxon signed test for nodule consistency, p<0.01). On
      1mm CT images there was significantly higher agreement regarding nodule
      consistency than on 5mm CT (kappa=0.78 and 0.67, respectively). CONCLUSIONS:
      Concurrent use of thin-section and thick-section CT can provide more accurate
      nodule assessment and higher interobserver agreement in SSPN.

PMID- 19103342
TI  - Management of airway involvement of oesophageal cancer using covered retrievable
      nitinol stents.
AB  - AIM: To assess the efficacy and safety of covered retrievable nitinol stents in
      oesophageal cancer patients with airway involvement. MATERIALS AND METHODS: Under
      fluoroscopic guidance, covered retrievable nitinol airway stents were placed in
      23 oesophageal cancer patients with airway stricture and/or oesophagorespiratory
      fistula (ERF) over a long period of 12 years. Six patients only had aspiration by
      ERF and three patients had both airway stricture and asymptomatic ERF. Technical
      aspects, dyspnoea improvement, and/or resolution of ERF symptoms, complications,
      reinterventions, and survival data were evaluated. RESULTS: A total of 27 airway
      stents (14 tracheal, 11 bronchial, and two hinged) were placed successfully in 23
      patients with airway stricture or ERF. Dyspnoea score decreased significantly
      after stent placement (p<0.001). ERF were sealed off in all nine patients.
      Complications included stent migration or expectoration (n=4), haemoptysis (n=2),
      sputum retention (n=7), and tumour overgrowth (n=1). All three migrated stents
      were easily removed. Twenty-one patients died, with the median survival period of
      76 days (range 2-197 days). CONCLUSION: Placement of covered retrievable
      expandable nitinol stents was safe and effective for the palliative treatment of
      airway strictures and/or ERF, with a reasonable range of complications, in
      patients with advanced oesophageal cancer.

PMID- 19103343
TI  - Audit of the introduction of CT colonography for detection of colorectal
      carcinoma in a non-academic environment and its implications for the national
      bowel cancer screening programme.
AB  - AIM: To compare the sensitivity of double-contrast barium enema (DCBE) with
      computed tomography colonography (CTC) to determine whether CTC is superior for
      the detection of colorectal cancer (CRC) locally, and to compare the results to
      those of a national barium enema audit. MATERIALS AND METHODS: All patients
      undergoing diagnostic DCBE or CTC between January 2003 and December 2005 were
      identified from the picture archiving communication system (PACS). Patients with
      a confirmed diagnosis of CRC were identified from the local cancer registry.
      Patients who were not diagnosed as having CRC on imaging were assumed true
      negatives if they were not listed in the cancer registry by December 2007, giving
      a minimum of 2 years follow-up. DCBE and CTC reports of all patients with CRC
      were analysed, and cancer detection was considered to have occurred (positive
      test result) if the report stated the definite presence of CRC or possible CRC
      requiring further investigation. RESULTS: 2520 DCBEs and 604 CTCs were included.
      Twenty-one of 33 patients with CRC were detected using DCBE (incidence 1.31%,
      sensitivity 63.7%). Thirty-two of 33 patients with CRC were -detected using CTC
      (incidence 5.46%, sensitivity 97.7%). CONCLUSION: CTC is more sensitive for the
      detection of CRC, and its introduction in a district general hospital is
      justified. However, there has been a consequent decline in DCBE sensitivity,
      which, if reflected nationally, suggests CTC is the preferential screening test
      for CRC.

PMID- 19103344
TI  - Ultrasonography for suspected deep vein thrombosis: how useful is single-point
      augmentation?
AB  - AIMS: To assess the role of single-point augmentation of spectral Doppler flow in
      the diagnosis of acute deep vein thrombosis (DVT). Secondary objectives included
      identifying the augmentation response in non-DVT diagnoses. METHODS: Patients
      attending the ultrasound departments of two hospitals for investigation of
      suspected acute DVT during an 8-month period were recruited to the study group.
      Spectral Doppler assessment of the superficial femoral vein was recorded during
      Valsalva and calf compression manoeuvres in the asymptomatic and symptomatic
      legs. The Doppler waveforms from the symptomatic limb were characterized as
      "normal" or "abnormal" by the operator. Standard compression ultrasonography of
      the symptomatic leg was then performed with the presence of DVT or an alternative
      diagnosis documented. RESULTS: One hundred and sixty-seven patients underwent
      ultrasound examinations using the study methodology. Nine patients were
      subsequently excluded due to bilateral DVT or inability to tolerate calf
      compression. The mean age of the remaining 158 patients was 65.4 years with 28
      DVTs identified (18% of patients). Calf compression elicited a normal response in
      118/130 of non-DVT examinations (specificity 91%) and an abnormal response in
      18/28 DVT examinations (sensitivity 64%). Diminished or absent augmentation was
      identified in alternative diagnoses that included haematoma and Baker's cyst.
      CONCLUSIONS: This study demonstrates that single-point augmentation has a low
      sensitivity in suspected lower-limb DVT, and that the majority of undetected DVTs
      are isolated to the calf veins. An abnormal augmentation response is a poor
      predictor of lower-limb DVT as alternative diagnoses can produce diminished or
      reduced augmentation. Therefore, single-point augmentation does not add to the
      standard compression ultrasound examination for suspected DVT and should not be
      routinely performed.

PMID- 19103345
TI  - Diagnostic yield of MRI for audiovestibular dysfunction using contemporary
      referral criteria: correlation with presenting symptoms and impact on clinical
      management.
AB  - AIM: To investigate the diagnostic yield of T2-weighted magnetic resonance
      imaging (MRI) screening for vestibular schwannoma and other relevant conditions
      in the setting of audiovestibular symptoms, given the more liberal contemporary
      referral criteria. To determine whether presenting clinical symptoms correlate
      with imaging outcome in order to guide future protocols for MRI referral.
      MATERIALS AND METHODS: Eight hundred and eighty-one consecutive MRI examinations
      performed in patients with audiovestibular dysfunction were reviewed. Clinical
      indications and findings were recorded. Case notes were reviewed in patients with
      positive imaging findings. Two-way, cross-tabulation, Chi-square analysis was
      performed to assess the relationship between presenting symptoms and imaging
      outcome. RESULTS: Twelve of the 881 (1.4%) were positive for vestibular
      schwannoma. A further four of 881 (0.4%) revealed other relevant conditions.
      Incidental conditions, felt to be irrelevant to the presenting symptoms, were
      noted in 12 of the 881 (1.4%). In all 12 cases that were positive for vestibular
      schwannoma, either tinnitus or hearing loss was present. CONCLUSION: The yield
      for T2-weighted MRI to diagnose vestibular schwannoma and other relevant
      retrocochlear conditions was lower than for previous studies, which is likely to
      reflect trends in referral criteria. No single audiovestibular symptom or
      combination of symptoms is a statistically significant predictor of imaging
      outcome.

PMID- 19103346
TI  - Evaluation of non-target arterial patency after implantation of hepatic arterial
      catheter using a modified implantation technique with the fixed catheter tip
      method.
AB  - AIM: To retrospectively investigate persistent hepatofugal blood flow in the
      gastroduodenal artery after implantation of a port-catheter system for repeated
      hepatic arterial infusion chemotherapy using a modified fixed catheter tip
      method. MATERIALS AND METHODS: A port-catheter system was percutaneously
      implanted in 150 patients (90 men and 60 women; mean age 64.6 years) with
      unresectable liver cancer. The persistence of blood flow beyond the end hole of
      the indwelling catheter via the port obtained immediately and 1-10 days after
      port-catheter placement was investigated using arteriography. RESULTS: In all
      cases, port-catheter placement was successfully performed. In 64 (42.7%) of the
      150 participants, the gastroduodenal artery was detected on arteriography just
      after implantation. However, arteriography obtained 1-10 days (mean 4.3 days)
      after implantation revealed the gastroduodenal artery in only two of the 64
      participants. In these two patients, persistent blood flow disappeared
      spontaneously 12 and 15 days after implantation, respectively. CONCLUSION:
      Closure of the lumen of the distal tip of the catheter beyond the side hole most
      often occurs spontaneously just after implantation. However, the findings of the
      present study indicate that closure will occur within 15 days at the latest. This
      suggests that delaying chemotherapy for about 2 weeks after implantation may be
      advisable.

PMID- 19103347
TI  - Adult prostate sarcoma: radiological-clinical correlation.
AB  - AIM: To describe the imaging features and the correlation with clinical findings
      of adult prostate sarcoma. MATERIALS AND METHODS: Radiological data of seven
      adult male patients with prostate sarcoma, documented by pathological examination
      of specimens, were analysed retrospectively. Radiological features were
      correlated with clinical and pathological findings. RESULTS: The mean age of the
      study population was 45.8 years (range 21-76 years). The mean value of the serum
      prostate specific antigen (PSA) in seven patients was 1.59 ng/ml (range 0.735
      3.72 ng/ml). Five patients had leiomyosarcomas and two had rhabdomyosarcomas. The
      most common symptom was urinary obstruction (n=7) and the most common sign was
      the markedly enlarged prostate as revealed by digital rectal examination (n=7).
      The mean size of the tumours was 8.7 x 7.2 x 7 cm (range 6.5 x 5x 6.5 to 12.1 x
      10.2 x 8.9 cm). Tumours were round (n=4), lobular (n=2), or irregular (n=1). Two
      tumours occupied the majority of the prostate and five occupied the entire
      prostate. One tumour appeared as a homogeneous mass, and six tumours contained
      cystic areas on computed tomography (CT) and magnetic resonance imaging (MRI).
      Tumours enhanced avidly on contrast-enhanced CT (n=5) and MRI (n=2). Magnetic
      resonance spectroscopy (MRS; n=2) showed the ratio of choline:citrate to be 1.6
      and 10.75. Tumour invasion was present in the bladder (n=3) and rectum (n=1).
      CONCLUSIONS: Adult prostate sarcoma was characteristically shown to be a large
      and heterogeneous mass with rapid, hypervascular and heterogeneous enhancement on
      CT and MRI. The main MRS feature was a marked increase in the choline:citrate
      ratio. The clinical manifestations corresponded mainly to local mass effects and
      tumour invasion.

PMID- 19103348
TI  - Prediction of the presence of invasive disease from the measurement of extent of
      malignant microcalcification on mammography and ductal carcinoma in situ grade at
      core biopsy.
AB  - AIM: To determine whether the extent of microcalcification and ductal carcinoma
      in situ (DCIS) grade can be used to accurately predict the presence and size of
      invasive cancer in cases of malignant microcalcification. MATERIALS AND METHODS:
      Over a 10-year period, 402 cases of malignant microcalcification from an NHS
      screening programme were analysed. For each case, measurement of mammographic
      microcalcification extent, DCIS grade, and the presence and size of invasive
      carcinoma from the excised surgical specimen were recorded. RESULTS: The final
      histological diagnosis was DCIS only in 71% (284/402) and DCIS with a focus of
      invasive disease in 29% (118/402). The risk of invasive disease increased with
      increasing size of microcalcification from 20% (27/136) for cluster size less
      than 11mm, to 45% (18/40) for cluster size more than 60mm. The risk of invasive
      disease also increased with increasing histological grade of DCIS from 13% (4/31)
      with low-grade DCIS to 36% (86/239) with high-grade DCIS. There were significant
      associations with the presence of invasive disease for cluster size (p=0.0001)
      and DCIS grade (p=0.003), and when using univariate analysis with simple [cluster
      size (p=0.01) and grade (p=0.01)] and multiple [cluster size (p=0.02) and grade
      (p=0.02)] logistic regression, respectively. The Hosmer-Lemeshow goodness-of-fit
      test suggests that the multiple logistic regression model has a good fit
      (p=0.99). CONCLUSION: The multidisciplinary team can use these data in individual
      cases to estimate the risk of invasive cancer and decide whether to carry out an
      axillary staging procedure.

PMID- 19103349
TI  - Isolated perihepatic tuberculosis: imaging findings.
AB  - AIM: To review the imaging findings of isolated perihepatic tuberculosis without
      coexistent active tuberculosis elsewhere in the body. MATERIALS AND METHODS: Over
      a 9-year period, six patients with histopathologically proven perihepatic
      tuberculosis without simultaneous active tuberculosis elsewhere in the body were
      included in this study. Two radiologists retrospectively evaluated in consensus
      the location (right, left, or both perihepatic spaces), size (maximum diameter),
      morphology (ovoid or round), number, attenuation (low-, iso-, or high-attenuation
      compared with the adjacent liver parenchyma), and the presence or absence of
      contrast enhancement of the lesions on computed tomography (CT), and echogenicity
      (low-, iso-, or high-echogenicity compared with the adjacent liver parenchyma) of
      the lesions on ultrasonography. RESULTS: On CT, an isolated perihepatic lesion
      was located in the right perihepatic space in five patients, whereas three
      lesions were located in both perihepatic spaces in the remaining patient. The
      mean maximum diameter of the isolated perihepatic tuberculosis lesions was 29.7
      mm. Isolated perihepatic tuberculosis appeared as an ovoid-shaped, homogeneous,
      and low-attenuating (n=5) or high-attenuating (n=1) lesion relative to the liver.
      There was peripheral rim enhancement of the lesion in two patients. On
      ultrasonography, isolated perihepatic tuberculosis was revealed as a homogeneous,
      low-echoic (n=5) or iso-echoic (n=1) lesion relative to the liver. CONCLUSION:
      Although various inflammatory or malignant lesions can be located in the
      perihepatic space, isolated perihepatic tuberculosis appears an ovoid-shaped,
      homogeneous, and low-attenuating or low-echoic lesion compared with the liver
      parenchyma on CT or ultrasonography.

PMID- 19103350
TI  - The appendix on CT.
AB  - Appendicitis can be a difficult clinical diagnosis to make. A negative
      appendicectomy rate of 20% has traditionally been accepted as the consequences of
      appendiceal perforation can be grave. Cross-sectional imaging is increasingly
      being employed in the investigation of adults with suspected appendicitis. This
      review will demonstrate the appearance of the normal appendix on computed
      tomography (CT) and its appearance in a range of inflammatory and neoplastic
      processes including appendicitis, Crohn's disease, infections, and benign and
      malignant tumours.

PMID- 19103351
TI  - Imaging findings of unusual intra- and extrahepatic portosystemic collaterals.
AB  - We describe unusual portosystemic shunts demonstrated using computed tomography
      (CT) and magnetic resonance imaging (MRI), including gallbladder varices,
      aberrant left gastric vein to left portal vein collaterals, intrahepatic and
      transhepatic portosystemic venous shunt, and mesenteric varices. Familiarity with
      the CT and MRI features of unusual portosystemic shunts will help in making the
      correct diagnosis for affected patients.

PMID- 19103352
TI  - MRI of brachial plexopathies.
AB  - Magnetic resonance imaging (MRI) has become the primary imaging technique in the
      evaluation of brachial plexus pathology, and plays an important role in the
      identification, localization, and characterization of the cause. Improvements in
      MRI technique have helped in detecting changes in the signal intensity of nerves,
      subtle enhancement, and in detecting perineural pathology, thereby refining the
      differential diagnosis. The present review of the visualization of brachial
      plexus abnormalities using MRI is based on a review of 26 cases. The causes
      include trauma and a spectrum of non-traumatic causes, such as acute
      idiopathic/viral plexitis, metastases, immune-mediated plexitis, and mass lesions
      compressing the brachial plexus.

PMID- 19103354
TI  - RE: Considerations when introducing a new cardiac MDCT service. Avoiding the
      pitfalls.

PMID- 19103355
TI  - Re: The role of specialist neuroradiology second opinion reporting: is there
      added value?

PMID- 19103357
TI  - Editor's annual report.

PMID- 19103358
TI  - Blue (or purple) toe syndrome.
AB  - The blue (or purple) toe syndrome consists of the development of blue or
      violaceous discoloration of one or more toes in the absence of obvious trauma,
      serious cold-induced injury, or disorders producing generalized cyanosis. The
      major general categories are: (1) decreased arterial flow, (2) impaired venous
      outflow, and (3) abnormal circulating blood. Depending on its pathogenesis, the
      discoloration may be blanching or nonblanching. An accurate diagnosis is
      critical, because many of the causes threaten life and limb, but the patient's
      medical history, accompanying nondermatologic findings on physical examination,
      and a discriminating use of laboratory tests are usually more important than the
      nature of the cutaneous abnormalities in determining the cause. LEARNING
      OBJECTIVES: After completing this learning activity, participants should be able
      to define the blue (or purple) toe syndrome, categorize the causes, and recognize
      the important historical, clinical, and laboratory findings that differentiate
      the causes and lead to the correct diagnosis.

PMID- 19103359
TI  - A gender gap in the dermatology literature? Cross-sectional analysis of
      manuscript authorship trends in dermatology journals during 3 decades.
AB  - BACKGROUND: Despite a dramatic influx of female dermatologists during the last 30
      years, women in academic dermatology departments remain relatively clustered in
      junior faculty positions. Research in other specialties showing a disparity in
      the academic productivity of women has led to many hypotheses regarding factors
      that may place them at a competitive disadvantage. It is unknown, however,
      whether similar differences in academic productivity might also serve as barriers
      to advancement in dermatology, or whether any productivity gap actually exists in
      this specialty that experienced a more substantial entry of women. OBJECTIVE:
      Because publication in peer-reviewed journals is one of the core measures of
      academic productivity used in the promotion process, we evaluated trends in the
      prevalence of female authorship in top dermatology journals during the last 3
      decades. METHODS: We conducted an observational study of trends in the sex
      distribution of US authors in 3 prestigious general dermatology journals (in
      1976, 1986, 1996, and 2006) and 3 subspecialty dermatology journals (in 2006
      only). Journals were chosen based on published impact factors and citation half
      lives. RESULTS: During the last 3 decades, the proportion of women authoring
      manuscripts in the 3 major general dermatology journals increased from 12% to 48%
      of US-affiliated first authors (P < .001) and from 6.2% to 31% of US-affiliated
      senior authors (P < .001). Separate analyses by journal and by article type
      showed similar increases. The prevalence of female authors in subspecialty
      journals in 2006 was slightly more variable. LIMITATIONS: Although the
      publications selected for this study capture many of the most respected US
      journals in dermatology, they may not be representative of all journals in which
      dermatologists publish. CONCLUSIONS: Female dermatologists are authoring
      publications in growing numbers that match or exceed their prevalence in the
      academic and overall workforce. This suggests that other factors (differences in
      productivity outside of the publishing arena, differences in job descriptions or
      opportunities, differences in career aspirations, a lack of institutional support
      or flexibility, or gender bias) may be associated with the ongoing reduced
      advancement of women to senior academic dermatology ranks relative to their male
      colleagues, and further research is warranted to explore these possibilities.

PMID- 19103360
TI  - Narrowband ultraviolet B and medium-dose ultraviolet A1 are equally effective in
      the treatment of moderate to severe atopic dermatitis.
AB  - BACKGROUND: Phototherapy may be effective in atopic dermatitis (AD). Medium-dose
      (MD) ultraviolet (UV) A1 was introduced for the treatment of AD. Few
      immunohistochemical data are available pertaining to phototherapy in AD.
      Regulatory T cells may play a role in clearing AD. OBJECTIVES: We sought to
      compare the clinical and immunohistochemical effects of narrowband (NB) UVB and
      MD UVA1 treatment in patients with AD. METHODS: Thirteen adult patients with AD
      were included in this randomized investigator-blinded half-sided comparison study
      between NB UVB and MD UVA1. Disease activity was measured using the Leicester
      sign score. Skin biopsy specimens were taken before and after phototherapy.
      Regulatory T cells were stained with the forkhead box protein P3 (FoxP3).
      RESULTS: NB UVB and MD UVA1 both significantly decreased AD severity (P < .01)
      and the dermal cellular infiltrate. The percentage of FoxP3(+)CD3(+) T cells did
      not change after NB UVB or MD UVA1 treatment. LIMITATION: MD UVA1 therapy was
      given 3 times per week instead of the preferred regimen of 5 times per week. This
      was necessary to achieve good blinding of the study. CONCLUSIONS: NB UVB and MD
      UVA1 seem equally effective in the treatment of patients with moderate to severe
      AD. Neither MD UVA1 nor NB UVB had an effect on the percentage of FoxP3(+)CD3(+)
      T cells.

PMID- 19103361
TI  - Mohs micrographic surgery histopathology concordance.
AB  - BACKGROUND: The low recurrence rate and tissue-sparing benefit associated with
      Mohs micrographic surgery (MMS) requires accurate interpretation of frozen
      sections by the MMS surgeon. OBJECTIVE: We sought to assess concordance between
      dermatopathologists and MMS surgeons when reporting cutaneous malignancy in the
      MMS setting. METHODS: This study is a retrospective analysis of 1156 slides
      submitted during 10 years as part of a pre-existing randomized, blinded, quality
      assurance protocol. Slides were read by one of 5 dermatopathologists and
      represent cases from 3 MMS surgeons and 5 MMS fellows. Agreement or disagreement
      was recorded. RESULTS: Of the 1156 slides, 32 slides (2.8%) were disparate. Aside
      from differences regarding intraepidermal neoplasia, the concordance rate was
      99.7%. LIMITATIONS: This study represents data collected at a single institution
      in the United States alone. CONCLUSION: There was statistically significant
      concordance between MMS surgeons and dermatopathologists in frozen section
      interpretation in the MMS setting. Discordance was primarily related to the
      interpretation of in situ malignancy.

PMID- 19103362
TI  - Expression pattern of p75 neurotrophin receptor protein in human scalp skin and
      hair follicles: Hair cycle-dependent expression.
AB  - BACKGROUND: The p75 neurotrophin receptor (p75NTR) is a death factor (apoptosis
      promoting protein) that belongs to the tumor necrosis factor receptor superfamily
      of membrane proteins. In the murine hair follicle (HF) model, p75NTR plays a
      critical role during HF morphogenesis, functioning as a receptor that negatively
      controls HF development. p75NTR signaling is involved in the control of
      keratinocyte apoptosis during catagen. To date, knowledge about the expression
      pattern of p75NTR protein in human scalp skin and HFs is limited. In this
      investigation we hypothesized that p75NTR protein is expressed in human scalp
      skin and its expression in HFs fluctuates with the transitions from anagen -->
      catagen --> telogen stages. METHODS: To test this hypothesis, the
      immunoreactivity of p75NTR protein was examined in human scalp skin by
      immunofluorescent and immunoalkaline phosphatase methods. A total of 50 normal
      appearing human scalp skin biopsy specimens were examined (healthy women age 53
      57 years). In each case, 50 HFs were analyzed (35, 10, and 5 follicles in anagen,
      catagen, and telogen, respectively). RESULTS: We found variations in p75NTR
      protein expression with HF cycling. p75NTR expression was negligible in early,
      mid, and mature anagen and weak during late anagen. p75NTR expression was
      moderate during anagen-catagen transition. It was strong in both catagen and
      telogen HF. Also, p75NTR protein expression was strong in the stratum corneum
      (epidermis), dermal fibroblasts, blood vessels, nerve endings, adipocytes, and
      both sebaceous and sweat glands. LIMITATIONS: Our knowledge about other proteins
      (prosurvival and pro-apoptotic molecules) interacting with p75 is incomplete.
      CONCLUSIONS: Our investigation reports, for the first time, the expression
      patterns of p75NTR in human scalp skin and HFs. p75NTR protein expression
      exhibited significant hair cycle-dependent fluctuation, suggesting a possible
      role in human HF biology.

PMID- 19103363
TI  - Treatment of intertriginous psoriasis: from the Medical Board of the National
      Psoriasis Foundation.
AB  - BACKGROUND: Involvement of areas of the skin fold is common in patients with
      psoriasis although the exact incidence is unknown. This report summarizes studies
      regarding the therapy of intertriginous psoriasis. OBJECTIVE: A task force of the
      National Psoriasis Foundation Medical Board was convened to evaluate treatment
      options. Our aim was to arrive at a consensus on therapy for intertriginous or
      inverse psoriasis. METHODS: Reports in the literature were reviewed regarding
      psoriasis affecting the skin-fold areas and its therapy. LIMITATIONS: There are
      few evidence-based studies on the treatment of intertriginous psoriasis. RESULTS:
      The recommended short-term (2-4 weeks) therapy for inverse psoriasis is low- to
      mid-potency topical steroids. For long-term therapy, topical calcipotriene
      (calcipotriol) or one of the immunomodulating agents, pimecrolimus or tacrolimus,
      is favored. CONCLUSIONS: Low- to mid-potency topical steroids are recommended as
      first-line, short-term treatment. It is recommended that their use should either
      be of limited duration (less than 2-4 weeks) or that the lowest effective
      strength be used intermittently for long-term care to minimize the potential for
      risks. Calcipotriene (calcipotriol), pimecrolimus, and tacrolimus, while not as
      highly efficacious as topical steroids, are associated with fewer long-term risks
      and are therefore recommended for long-term therapy when feasible.

PMID- 19103364
TI  - Basosquamous carcinoma.
AB  - BACKGROUND: Basosquamous carcinoma is considered an aggressive type of basal cell
      carcinoma (BCC) with an increased risk of recurrence and metastases. This concept
      has been perpetuated in the literature in spite of confusing terminology, limited
      scientific data, and the contradictory surgical experiences of some observers.
      METHODS: This is a narrative review based on a MEDLINE search of articles in
      English and a manual search of popular dermatology textbooks to define
      basosquamous carcinoma, its incidence, clinical behavior, and treatment of
      choice. RESULTS: There are no specific clinical features to distinguish
      basosquamous carcinoma from other BCC types and the diagnosis is made only after
      biopsy. There are several histologic definitions of basosquamous carcinoma
      ranging from a characteristic combination of BCC and squamous cell carcinoma with
      or without a transition zone, to any BCC with evidence of keratinization. The
      authors confine the use of the term to an infiltrative growth BCC with areas of
      keratinization and/or intercellular bridge formation in the setting of a
      prototypic proliferative stromal reaction. The term "metatypical basal cell
      carcinoma" is considered a synonym but its use is discouraged for the reasons
      outlined. The reported incidence of basosquamous carcinoma ranges from 1.2% to
      2.7%. Published recurrence rates are 12% to 51% for surgical excision and 4% for
      Mohs micrographic surgery. The incidence of metastasis is at least 5%. The
      aggressive biological behavior and clinical course distinguish basosquamous
      carcinoma from other forms of BCC. LIMITATIONS: This study is a literature
      review, contains a limited number of patients, and is mostly retrospective
      studies. CONCLUSION: The terminology surrounding basosquamous carcinoma is
      confusing and there is a need for more uniform language. Based on our review and
      personal experience, we propose a more precise and specific definition. Data
      regarding the incidence, recurrence, and metastasis rates of basosquamous
      carcinoma are based mostly on retrospective series with a limited number of
      cases. We conclude that although the incidence of basosquamous carcinoma is
      unknown, there is a literature precedent suggesting more aggressive biological
      behavior. We believe that complete surgical excision is the preferred approach,
      and that basosquamous carcinoma is an ideal candidate lesion for Mohs
      micrographic surgery.

PMID- 19103365
TI  - Hemangiomas and thyroid disease.

PMID- 19103366
TI  - Drug-induced hypersensitivity syndrome: drug reaction with eosinophilia and
      systemic symptoms (DRESS) syndrome induced by aspirin treatment of Kawasaki
      disease.
AB  - Drug-induced hypersensitivity syndrome (DIHS), also known as drug reaction with
      eosinophilia and systemic symptoms (DRESS), is a severe multiple-organ condition
      caused by drug treatment. The current report describes a Japanese boy who
      underwent aspirin treatment for Kawasaki disease, and who subsequently presented
      with the manifestations of DIHS/DRESS syndrome. He had been treated with a single
      high dose of intravenous immunoglobulin and aspirin orally for Kawasaki disease.
      One month after the onset of Kawasaki disease, he developed a generalized
      maculopapular eruption, high-grade fever, leukocytosis with eosinophilia, and an
      increased number of atypical lymphocytes, severe liver dysfunction,
      lymphadenopathy, and prominent increases in antihuman herpesvirus-6
      immunoglobulin G titer. The activity of 2',5'-oligoadenylate synthetase was
      elevated at the onset stage. Hypersensitivity to aspirin was confirmed by skin
      patch test and by lymphocyte stimulation test. Based on these findings, the
      patient was diagnosed with DIHS/DRESS caused by aspirin. To our knowledge, there
      have been no previous reports of aspirin-induced hypersensitivity syndrome
      subsequent to Kawasaki disease. The activity of 2',5'-oligoadenylate synthetase
      might be useful as a diagnostic marker of DIHS/DRESS syndrome and for exploring
      its pathogenesis.

PMID- 19103367
TI  - Febrile ulceronecrotic Mucha-Habermann disease associated with herpes simplex
      virus type 2.
AB  - Febrile ulceronecrotic Mucha-Habermann disease is a rare severe variant of
      pityriasis lichenoides et varioliformis acuta, a disease within the pityriasis
      lichenoides spectrum of disorders. It remains uncertain whether these disorders
      are preneoplastic or reactive against infectious or other antigenic stimuli.
      Febrile ulceronecrotic Mucha-Habermann disease varies in severity and may be
      accompanied by a range of systemic symptoms. We present a case associated with
      herpes simplex virus infection. In this case, no significant T cell clone was
      identified. Clonality may be a prognostic marker, but reports with T-cell
      receptor polymerase chain reaction results are limited to eight previous cases,
      and further reports are required. Awareness of the condition is important because
      of its fulminant potential.

PMID- 19103368
TI  - A case of syringotropic cutaneous T-cell lymphoma treated with local
      radiotherapy.
AB  - Syringotropic cutaneous T-cell lymphoma (SCTCL) is a variant of mycosis fungoides
      that is characterized by the presence of lymphocytic infiltration of eccrine
      glandular structures and the absence of the classic features of MF, such as
      epidermotropism and Pautrier's microabscesses. We report a patient with SCTCL who
      presented with multiple hypopigmented patches and localized alopecia who was
      treated with local radiotherapy with excellent local control. In our experience,
      local electron radiation offers local control in early stage SCTCL, and it may be
      possible to reserve systemic therapy for more advanced stages of the disease.

PMID- 19103369
TI  - Folliculitis-perifolliculitis related to erlotinib therapy spares previously
      irradiated skin.
AB  - Erlotinib, a specific epidermal growth factor receptor tyrosine kinase inhibitor,
      is used to treat various metastatic cancers. It is known to cause an acneiform
      rash. Herein, we report a case where the rash spared the previous radiotherapy
      field. A limitation of this study is that it is an anecdotal case report. Further
      research into the pathologic process of the rash is warranted to understand the
      reason for its absence in the irradiated skin.

PMID- 19103370
TI  - Primary cutaneous Richter syndrome: prognostic implications and review of the
      literature.
AB  - The term Richter syndrome (RS) describes the transformation of chronic
      lymphocytic leukemia into a high-grade lymphoma. RS occurs in 3% to 10% of
      chronic lymphocytic leukemia cases, and its onset is often characterized by the
      abrupt development of systemic symptoms (eg, fever in the absence of infection,
      night sweats, and weight loss), progressive lymphadenopathy, and
      hepatosplenomegaly. RS frequently arises in the lymph nodes or bone marrow, and
      rarely presents with extranodal involvement, which includes the gastrointestinal
      tract, eye, testis, central nervous system, lung, kidney, and skin. We review the
      literature regarding the clinical course and treatment of RS, present a patient
      with primary cutaneous RS, and discuss the prognostic implications.

PMID- 19103371
TI  - Alopecia areata incognita: true or false?

PMID- 19103372
TI  - Melanoidins-sunscreens: dihydroxyacetone with or without naphthoquinones.

PMID- 19103373
TI  - Methotrexate for the treatment of generalized lichen planus.

PMID- 19103374
TI  - Adherence to topical hydrocortisone 17-butyrate 0.1% in different vehicles in
      adults with atopic dermatitis.

PMID- 19103375
TI  - Solitary fixed drug eruption caused by finasteride.

PMID- 19103376
TI  - Trichodysplasia of immunosuppression treated with oral valganciclovir.

PMID- 19103377
TI  - Treatment of cutaneous pseudolymphoma with interferon alfa-2b.

PMID- 19103378
TI  - An unusual case of swimmer's itch.

PMID- 19103382
TI  - Santa's down: think with your head, not with your heart.

PMID- 19103384
TI  - Central command.

PMID- 19103385
TI  - No more guessing.

PMID- 19103386
TI  - Train like you mean it: how we prepare is just as important as why.

PMID- 19103387
TI  - Splat: a pro's answer to bug guts.

PMID- 19103388
TI  - A dirty job: compartment syndrome in a confined-space rescue.

PMID- 19103389
TI  - 'Tis the flu season: do we get paid when we're sick?

PMID- 19103391
TI  - Empowering the patient: after-care instructions reduce calls & improve quality of
      life.

PMID- 19103392
TI  - Watch your step: EMS response to construction accidents.

PMID- 19103393
TI  - A tight squeeze: airway management for the limited-access patient.

PMID- 19103394
TI  - Cartoon 'correctiveness'.

PMID- 19103396
TI  - Precordial thump: friend or enemy?

PMID- 19103397
TI  - Long-term outcome of bystander-witnessed out-of-hospital cardiac arrest in
      Estonia from 1999 to 2002.
AB  - OBJECTIVE: To assess the long-term outcome of bystander-witnessed out-of-hospital
      cardiac arrest victims in Estonia by using the survival rate and quality of life
      assay. METHODS: All resuscitation attempts made from 01.01.1999 to 31.12.2002 in
      Estonia were retrospectively screened for bystander-witnessed adult out-of
      hospital cardiac arrests of cardiac origin. The patients who survived hospital
      discharge were included in the study. Their long-term survival data were
      retrieved from Estonian Population Registry on March 15, 2004. Quality of life
      was assessed by RAND-36 questionnaire. Comparisons were made with population
      norms, and patients suffering from myocardial infarction or angina pectoris.
      RESULTS: 854 bystander-witnessed resuscitation attempts were made in four years.
      91 patients (10.7%) survived to hospital discharge. Their one-year survival rate
      was 77.0% and five-year survival rate 64.3%. 44 patients responded to quality of
      life questionnaire, sent 16-62 months after out-of-hospital cardiac arrest
      (response rate 77.2%). Respondents rated their quality of life significantly
      worse than general population in five out of eight categories. The out-of
      hospital cardiac arrest survivors with known cardiovascular disease in history
      (n=30) had quality of life similar to patients suffering from myocardial
      infarction or angina pectoris who had not required resuscitation. CONCLUSION: In
      Estonia majority of bystander-witnessed out-of-hospital cardiac arrest victims
      who survive hospital discharge are alive one and also more than three years after
      resuscitation. Their quality of life is worse than that of general population.

PMID- 19103398
TI  - Response to "crisis averted: important and unexpected lessons learnt from a
      simulated case of ventricular fibrillation".

PMID- 19103400
TI  - Adolescent health care.

PMID- 19103401
TI  - Development and clinical use of Rapid Assessment for Adolescent Preventive
      Services (RAAPS) questionnaire in school-based health centers.
AB  - INTRODUCTION: The purpose of this study is to describe the development and
      clinical use of Rapid Assessment for Adolescent Preventive Services (RAAPS), a
      time-efficient screening tool to assess for multiple adolescent risk behaviors.
      METHOD: A retrospective chart audit was conducted to obtain descriptive data of
      middle school (N = 106) and alternative high school (N = 39) adolescents who
      completed the 17- to 18-item RAAPS questionnaire. Surveys assessed providers'
      evaluations of the RAAPS. RESULTS: Descriptive statistics and qualitative
      analysis indicated that providers using the RAAPS were able to identify risk
      behaviors/factors, provide counseling for these behaviors, and refer 26% of 9- to
      15-year-olds and 43% of 16- to 20-year-olds for further assessment or ongoing
      risk counseling. In one brief clinic visit, the providers were able to address
      and document most risk behaviors/factors reported by the adolescents. DISCUSSION:
      Although psychometric analysis is needed, the RAAPS is a time efficient and
      comprehensive risk assessment tool. Early risk identification can assist
      providers in tailoring specific preventative education counseling and
      intervention programs that are geared to meet the specific needs of the
      adolescent population.

PMID- 19103402
TI  - Finding the balance: adolescents with type 1 diabetes and their parents.
AB  - INTRODUCTION: The purpose of this study was to describe the ways that parents and
      11- to 15-year-old teens communicate and the recurrent themes and patterns of
      behavior that were revealed during brief interactions about issues related to
      diabetes management. METHOD: A secondary qualitative analysis of data, based on a
      template for analysis developed from the literature, was completed on audiotaped
      interactions of 28 adolescents and their parents. RESULTS: Themes identified were
      frustration, fear, normalizing, trusting, and discounting. Trusting the
      adolescent to manage diabetes was difficult for the parents and was associated
      with frustration, fear, and discounting communication. DISCUSSION: Results
      support the need for clinicians to work with families to facilitate trust and
      positive parent-adolescent communication about diabetes management.

PMID- 19103403
TI  - Contraceptive use among adolescent Latinas living in the United States: the
      impact of culture and acculturation.
AB  - Although adolescent pregnancies have declined steadily during the past decade,
      Latina adolescents continue to have disproportionately high pregnancy rates. For
      nurse practitioners to effectively counsel this group of women concerning
      contraceptive use and sexual health, a basic understanding of the unique
      sociocultural factors influencing Latina adolescents' sexual activity is
      important. This article reviews recent literature concerning the effects of
      culture, acculturation, language, and significant relationships on Latina sexual
      behavior to provide recommendations for clinicians working with Latina
      adolescents in the primary care setting. Areas in need of further research are
      identified.

PMID- 19103404
TI  - Treating pediatric overweight through reductions in sedentary behavior: a review
      of the literature.
AB  - Reducing sedentary behavior has been proposed as a modality for treating
      pediatric overweight. Small randomized controlled trials suggest that targeting
      reductions in sedentary behavior, rather than targeting increases in physical
      activity, can be an effective modality in addressing this problem. In some cases,
      targeting reductions in sedentary behavior has been shown to be more effective
      than targeting physical activity directly, resulting in greater reductions in
      overweight measures such as body mass index and percent overweight. Reductions in
      sedentary behavior may allow more opportunity to reallocate this time to physical
      activity. It also may result in reduced intake of high-calorie foods. This
      article reviews the evidence in the literature for targeting reductions in
      sedentary behavior as a modality in treating pediatric overweight.

PMID- 19103405
TI  - Transition of the chronically ill youth with hemoglobinopathy to adult health
      care: an integrative review of the literature.
AB  - With the advent of innovative technologies and medical advances, more than a half
      million chronically ill youth (CIY) cross the threshold into adulthood yearly.
      Successful transition of the CIY with hemoglobinopathy (e.g., sickle cell,
      thalassemia) from pediatrics to adult care continues to be an inconsistent
      process. The purpose of undertaking a comprehensive empirical review was to
      synthesize the transition literature focusing on CIY with hemoglobinopathy and
      clinical recommendations. Among 17 studies critically reviewed and summarized,
      five studies focused on the CIY with hemoglobinopathy, and the remainder on youth
      with other chronic conditions. Further research on transition, especially for CIY
      with hemoglobinopathy, is needed.

PMID- 19103407
TI  - Galactorrhea in an adolescent girl.

PMID- 19103406
TI  - Ecstasy in the emergency department: MDMA ingestion.

PMID- 19103408
TI  - Childhood asthma practice guideline part three: update of the 2007 National
      Guidelines for the Diagnosis and Treatment of Asthma. The National Asthma
      Education and Prevention Program.

PMID- 19103409
TI  - Bicycle attachments for children: bicycle seats, trail-a-bikes, and trailers.

PMID- 19103410
TI  - Nurses without walls: field notes.

PMID- 19103411
TI  - Cultural proficiency, research, and evidence-based practice: implications for the
      nurse practitioner.

PMID- 19103412
TI  - JASMS Celebrates its 20(th) Birthday.

PMID- 19103415
TI  - Embryology of oesophageal atresia.
AB  - Esophageal atresia (OA) and tracheoesophageal fistula (TOF) are important human
      birth defects of unknown etiology. The embryogenesis of OA/TOF remains poorly
      understood, mirroring the lack of clarity of the mechanisms of normal
      tracheoesophageal development. The development of rat and mouse models of OA/TOF
      has allowed the parallel study of both normal and abnormal embryogenesis.
      Although controversies persist, the fundamental morphogenetic process appears to
      be a rearrangement of the proximal foregut into separate respiratory (ventral)
      and gastrointestinal (dorsal) tubes. This process depends on the precise temporal
      and spatial pattern of expression of a number of foregut patterning genes.
      Disturbance of this pattern disrupts foregut separation and underlies the
      development of tracheoesophageal malformations.

PMID- 19103416
TI  - Esophageal atresia repair with thoracotomy: the Cincinnati contemporary
      experience.
AB  - Esophageal atresia/tracheoesophageal fistula (EA/TEF) repair using an open muscle
      sparing thoracotomy has been the standard approach used in our institution.
      Whereas perioperative mortality is now very uncommon, short- and long-term
      morbidity is very common in these patients. However, the complexity of the
      esophageal anatomy and significant comorbidities appear to be important
      contributors to significant complications in these patients. At least 30% of the
      EA/TEF patients required esophageal dilatations for anastomotic stricture; this
      increased to 50% for patients with pure EA. Gastroesophageal reflux requiring an
      antireflux procedure was performed 23% of the time for EA/TEF and 30% for EA
      patients. In addition, there were a few complications, such as winging of the
      scapula and scoliosis, that were attributed in part to the utilization of a
      nonmuscle-sparing thoracotomy. The standard muscle-sparing thoracotomy remains a
      very versatile and useful approach to repairing esophageal atresia, and it is the
      standard for repairing more complex anatomical variants. The self-reported long
      term quality of life in these patients is very good, except for a few individuals
      with protracted feeding disorders and severe dysphagia.

PMID- 19103417
TI  - Esophageal atresia surgery in the 21st century.
AB  - The results of thoracoscopic repair of oesophageal atresia with or without
      tracheo-oesophageal fistula are presented. Twenty-six children had the repair
      performed thoracoscopically (22 in Edinburgh and 4 by Edinburgh surgeons in other
      institutions). Twenty infants had oesophageal atresia with tracheo-oesophageal
      fistula and 6 had isolated oesophageal atresia without fistula. Details of the
      technique are presented. Birth weights ranged from 1.4 to 3.9 kg and children
      were operated between 1 day and three months of age. There were 7 minor
      anastomotic leaks all managed conservatively, 1 recurrent fistula managed
      thoracoscopically and 9 anastomotic strictures. One child had a tracheo-bronchial
      fistula not seen at original thoracoscopy. There were 3 deaths (one child with
      Edward's syndrome, one with associated congenital diaphragmatic hernia and one
      late death with severe cardiac disease). Thoracoscopic repair of oesophageal
      atresia is feasible and the long term outcome appears favorable.

PMID- 19103418
TI  - Long-gap esophageal atresia treated by growth induction: the biological potential
      and early follow-up results.
AB  - This study had two purposes. The first was to determine whether the growth
      procedure would allow true primary repairs of the most severe end of the
      esophageal atresia (EA) spectrum with the longest gaps (LG) and most rudimentary
      lower esophageal segments. The second goal was to provide the first short- to mid
      term (3-12 years) follow-up data on the esophageal function and quality of life
      (QOL) data on the patients in this series. From our series of 60 LG-EA patients
      who underwent a growth procedure, 42 had the true primary esophageal repair
      completed 3 years ago. Among these, 18 had gaps over 6 cm, and for 6, only a
      rudimentary lower esophagus existed well below the diaphragm. No patient was
      turned down and all had primary repairs. These results suggest that even the most
      rudimentary segment has the potential to achieve normal size and that the full EA
      spectrum can have a primary repair. Our follow-up studies indicated that the
      esophageal function of these previously grown segments was very good. All
      contacted (40) were eating normally with only 3 receiving supplemental g-tube
      feeds because of other significant defects. We have actively treated significant
      reflux and 41/42 had fundoplication. By endoscopy (N = 15) no esophagitis was
      visible, but on biopsy, mild inflammation was found in 3. No conditions were
      found which would suggest that there would be a late deterioration or adverse
      consequences would arise. Based on these ongoing evaluations, the outlook seems
      very favorable for a good long-term QOL.

PMID- 19103419
TI  - Gastric transposition in children.
AB  - PURPOSE: To analyze the outcome in 192 children (116 males, 76 females)
      undergoing transposition since 1981. METHODS: The most common indications for
      esophageal replacement included failed repair of different varieties of
      esophageal atresia (138), caustic injury (29), and peptic strictures (9). A total
      of 81% of the patients were referred from other hospitals (50% from other
      countries). Age at operation ranged from 7 days to 17 years. The gastric
      transposition was performed by using blunt mediastinal dissection in 98 patients,
      with an additional 90 patients undergoing lateral thoracotomy. The retrosternal
      position was used in 4 patients. RESULTS: There were no graft failures, including
      those who had previously had failed gastric tube or Scharli operations.
      Anastomotic leaks occurred in 12% (all but one resolved spontaneously).
      Anastomotic stricture, requiring dilation developed in 20%. Half of these
      patients had previously sustained caustic esophageal injury. There were 9 deaths
      in the group (4.6%). One death occurred intraoperatively, 5 in the early
      postoperative period, and there were 3 late deaths. In over 90% of our patients,
      the outcome was considered good to excellent in terms of absence of swallowing
      difficulties or other gastrointestinal symptoms. Many children preferred to eat
      small frequent meals. Poor outcome was particularly associated with multiple
      previous attempts at esophageal salvage. There was no deterioration in the
      function of the gastric transposition in those patients followed for more than 10
      years. CONCLUSIONS: Gastric transposition for esophageal substitution is an
      acceptable procedure. It is attended by 4.6% mortality and a 12% leak rate. A
      total of 20% of the patients needed anastomotic dilation for stricture. In the
      long term, good function has been maintained. Gastric transposition compares
      favorably with other methods of esophageal replacement.

PMID- 19103420
TI  - Jejunum for bridging long-gap esophageal atresia.
AB  - OBJECTIVE: Exploring pros and cons of bridging long-gap esophageal atresia with
      an orthotopic jejunal pedicle graft. Retrospective series of 19 patients.
      METHODS: From 1988 through 2005, 19 patients with long-gap esophageal atresia
      received a jejunal graft. Median age at reconstruction was 76 days. The technique
      involved an initial right-sided thoracotomy or thoracoscopy to confirm the
      diagnosis of long-gap esophageal atresia. Through a median laparotomy, a small
      pediculated jejunal graft was prepared and placed transmesocolically and
      transhiatally in an orthotopic position in the right chest. RESULTS: All patients
      survived and none of the grafts were lost. Four intrathoracic and one
      intraabdominal leak occurred. One intrathoracic and one intraabdominal leak were
      surgically repaired. One early distal stenosis was reoperated as well. There were
      always signs of distal functional subobstruction, responding to dilation in all
      but one patient. Gastroesophageal reflux was not a problem except for one patient
      whose distal esophagus was eventually resected because of ongoing distal
      obstruction with dilation of the graft. Except for one patient, all patients are
      eating normally and most of them grow well. Respiratory problems were rare.
      Grafts did not become redundant and retained peristaltic activity. CONCLUSION:
      Orthotopic jejunal pedicle graft reconstruction of the esophagus in children is a
      demanding operation with considerably early morbidity but good long-term results.
      It should be part of the pediatric surgical armamentarium for reconstruction of
      the esophagus.

PMID- 19103421
TI  - Colonic replacement in cases of esophageal atresia.
AB  - Replacement of the esophagus in children is still a challenging problem; one of
      the major indications is failed esophageal atresia repair or long-gap ones. The
      colon is one of the best alternatives for replacement; long-term follow up has
      shown satisfactory results. In cases of complicated repair receiving frequent
      dilation and multiple operations, colon could be an alternative choice for these
      children to achieve normal swallowing.

PMID- 19103422
TI  - The surgical approach to esophageal atresia repair and the management of long-gap
      atresia: results of a survey.
AB  - The optimal approach for esophageal atresia (OA) repair and technique used for
      long-gap OA repair are controversial. There are few data comparing the outcomes
      of the different approaches and techniques. We performed a survey of current
      practice of 88 pediatric surgeons and asked experts to provide us with
      definitions and rationales behind their management strategies. There were no
      differences between UK and non-UK surgeons. Although the majority of pediatric
      surgeons perform minimally invasive surgery (68%), only 16% have performed
      thoracoscopic OA repair; however, 46% are planning to carry out thoracoscopic OA
      repair. Gastric interposition is the most preferred technique for long-gap OA
      when primary anastomosis is not possible, with 94% of those surgeons who use the
      technique satisfied with it. Growth of the esophageal ends by traction is the
      other major technique used, but only 76% of surgeons who use it are satisfied
      with it. Most surgeons repair < or =2 patients with long-gap OAs per year. Long
      gap OA should be managed by a limited number of surgeons at each center. Even
      among experts, there is little consensus on the definition of or the optimum
      technique for repair of long-gap OA.

PMID- 19103423
TI  - Outcome of esophageal atresia beyond childhood.
AB  - Survivors of esophageal atresia are reaching their adulthood in large numbers for
      the first time enabling assessment of true long-term outcome among this group of
      patients. This review summarizes the current knowledge on the subject focusing on
      late symptoms and complications, esophageal pathology and pulmonary function.
      Relationships between esophageal dysmotility, gastroesophageal reflux,
      esophagitis and epithelial metaplastic changes including esophageal cancer are
      outlined. In addition to pertinent literature, institutional experience, and
      follow-up of patients with esophageal atresia for more than 60 years is included.

PMID- 19103424
TI  - Tissue engineering: an option for esophageal replacement?
AB  - Esophageal replacement is required in several pediatric surgical conditions, like
      long-gap esophageal atresia. Although several techniques have been described to
      bridge the gap, all of them could be followed by postoperative complications.
      Esophageal tissue engineering could represent a valid alternative thanks to the
      recent advances in biomaterial science and cellular biology. Numerous attempts to
      shape a new esophagus in vitro have been described in the last decade. Herein, we
      review the main studies on the experimental use of nonabsorbable and absorbable
      materials as well as the development of cellularized patches. Furthermore, we
      describe the future perspectives of esophageal tissue engineering characterized
      by the use of stem cells seeded on new biopolymers. This opens to the
      construction of a functional allograft that could allow an anatomical replacement
      that grows with the children and does not severely impair their anatomy.

PMID- 19103425
TI  - Progress in gene transfer by germ cells in mammals.
AB  - Use of germ cells as vectors for transgenesis in mammals has been well developed
      and offers exciting prospects for experimental and applied biology, agricultural
      and medical sciences. Such approach is referred to as either male germ cell
      mediated gene transfer (MGCMGT) or female germ cell mediated gene transfer
      (FGCMGT) technique. Sperm-mediated gene transfer (SMGT), including its
      alternative method, testis-mediated gene transfer (TMGT), becomes an established
      and reliable method for transgenesis. They have been extensively used for
      producing transgenic animals. The newly developed approach of FGCMGT, ovary
      mediated gene transfer (OMGT) is also a novel and useful tool for efficient
      transgenesis. This review highlights an overview of the recent progress in germ
      cell mediated gene transfer techniques, methods developed and mechanisms of
      nucleic acid uptake by germ cells.

PMID- 19103426
TI  - Genetic analysis and fine-mapping of a dwarfing with withered leaf-tip mutant in
      rice.
AB  - A dwarf mutant of rice (Oryza sativa L.) by mutagenesis of ethylene
      methylsulfonate (EMS) treatment from Nipponbare was identified. The mutant
      exhibited phenotypes of dwarfism and withered leaf tip (dwl1). Based on the
      internode length of dwl1, this mutant belongs to the dm type of dwarfing.
      Analysis of elongation of the second sheath and alpha-amylase activity in
      endosperm showed that the phenotype caused by dwl1 was insensitive to gibberellin
      acid treatment. Using a large F2 population derived from a cross between the dwl1
      and an indica rice variety, TN1, the DWL1 gene was mapped to the terminal region
      of the long arm of chromosome 3. Fine-mapping delimited it into a 46 kb physical
      distance between two STS markers, HL921 and HL944, where 6 open reading frames
      were predicted. Cloning of DWL1 will contribute to dissecting molecular mechanism
      that regulates plant height in rice, which will be beneficial to molecular
      assisted selection of this important trait.

PMID- 19103427
TI  - Identification of karyopherin-alpha 2 as an Oct4 associated protein.
AB  - The POU domain transcription factor Oct4 is a master regulator in maintaining
      self-renewal and pluripotency of embryonic stem (ES) cells. To further explore
      the functional network of Oct4, the yeast two-hybrid system was used to search
      for Oct4 interacting proteins. PH domain (containing POU domain and homeodomain)
      of human OCT4 was used as a bait. From the human testis cDNA library, we
      identified a strong interaction between OCT4 and karyopherin-alpha 2 (KPNA-2).
      KPNA2 is involved in active nuclear import of proteins. This finding was
      confirmed by glutathione S-transferase pull-down and co-immunoprecipitation
      assays. The interaction between OCT4 and KPNA-2 was further mapped to multiple
      regions of the two proteins. In addition, we studied nuclear localization signal
      (NLS) of mouse Oct4 and demonstrated that it is essential for Oct4 nuclear
      localization. Thus, our data suggest that Oct4 nuclear localization may be
      mediated by its interaction with KPNA-2.

PMID- 19103428
TI  - Factors affecting mito-nuclear codon usage interactions in the OXPHOS system of
      Drosophila melanogaster.
AB  - Codon usage bias varies considerably among genomes and even within the genes of
      the same genome. In eukaryotic organisms, energy production in the form of
      oxidative phosphorylation (OXPHOS) is the only process under control of both
      nuclear and mitochondrial genomes. Although factors affecting codon usage in a
      single genome have been studied, this has not occurred when both interactional
      genomes are involved. Consequently, we investigated whether or not other factors
      influence codon usage of coevolved genes. We used Drosophila melanogaster as a
      model organism. Our chi2 test on the number of codons of nuclear and
      mitochondrial genes involved in the OXPHOS system was significantly different
      (chi2 = 7945.16, P < 0.01). A plot of effective number of codons against GC3s
      content of nuclear genes showed that few genes lie on the expected curve,
      indicating that codon usage was random. Correspondence analysis indicated a
      significant correlation between axis 1 and codon adaptation index (R = 0.947, P <
      0.01) in every nuclear gene sequence. Thus, codon usage bias of nuclear genes
      appeared to be affected by translational selection. Correlation between axis 1
      coordinates and GC content (R = 0.814, P < 0.01) indicated that the codon usage
      of nuclear genes was also affected by GC composition. Analysis of mitochondrial
      genes did not reveal a significant correlation between axis 1 and any parameter.
      Statistical analyses indicated that codon usages of both nDNA and mtDNA were
      subjected to context-dependent mutations.

PMID- 19103429
TI  - Simulation of gene pyramiding in Drosophila melanogaster.
AB  - Gene pyramiding has been successfully practiced in plant breeding for developing
      new breeds or lines in which favorable genes from several different lines were
      integrated. But it has not been used in animal breeding, and some theoretical
      investigation and simulation analysis with respect to its strategies, feasibility
      and efficiency are needed before it can be implemented in animals. In this study,
      we used four different pure lines of Drosophila melanogaster, each of which is
      homozygous at a specific mutant gene with a visible effect on phenotype, to
      simulate the gene pyramiding process and analyze the duration and population size
      required in different pyramiding strategies. We finally got the ideal
      individuals, which are homozygous at the four target genes simultaneously. This
      study demonstrates that gene pyramiding is feasible in animal breeding and the
      interaction between genes may affect the final results.

PMID- 19103430
TI  - Molecular characterization of LMW-GS genes from a somatic hybrid introgression
      line II-12 between Triticum aestivum and Agropyron elongatum in relation to quick
      evolution.
AB  - In order to exploit the evolution and find novel low-molecular-weight glutenin
      subunit (LMW-GS) for improvement of common wheat quality, thirteen variants from
      a somatic hybrid introgression line II-12 between Triticum aestivum cv. Jinan 177
      (JN177) and Agropyron elongatum were characterized via genomic PCR. Four clones
      were pseudogenes because they contained an internal stop codon. The remaining
      nine variants contained intact open reading frames (ORFs). Sequence alignment
      indicates that the proteins deduced from the nine ORFs have similar primary
      structure with LMW-GS cloned from its parents previously. However, they have some
      unique modifications in the structures. For example, EU292737 contains not only
      an extra Cys residue in the C-terminal domain but also a long repetitive domain.
      Both EU159511 and EU292738 start their first Cys residue in the N-terminal
      repetitive domain, but not in the N-conserved domain traditionally. These
      structural alterations may have positive contributions to wheat flour quality.
      The results of phylogeny showed that most LMW-GS variances from II-12 were
      homologous to those from parent JN177 and other wheat lines. The reason for quick
      evolution of LMW-GS in II-12 was discussed.

PMID- 19103431
TI  - QTL mapping in A-genome diploid Asiatic cotton and their congruence analysis with
      AD-genome tetraploid cotton in genus Gossypium.
AB  - Asiatic cotton (Gossypium arboreum L.) is an Old World cultivated cotton species.
      The sinense race was planted extensively in China. Due to the advances in
      spinning technology during the last century, the species was replaced by the New
      World allotetraploid cotton G. hirsutum L. Gossypium arboreum is still grown in
      India and Pakistan and also used as an elite in current cotton breeding programs.
      In addition, G. arboreum serves as a model for genomic research in Gossypium. In
      the present study, we generated an A-genome diploid cotton intraspecific genetic
      map including 264 SSR loci with three morphological markers mapped to 13 linkage
      groups. The map spans 2,508.71 cM with an average distance of 9.4 cM between
      adjacent loci. A population containing 176 F(2:3) families was used to perform
      quantitative trait loci (QTL) mapping for 17 phenotypes using Multiple QTL Model
      (MQM) of MapQTL ver 5.0. Overall, 108 QTLs were detected on 13 chromosomes.
      Thirty-one QTLs for yield and its components were detected in the F2 population.
      Forty-one QTLs for yield and its components were detected in the F(2:3) families
      with a total of 43 QTLs for fiber qualities. Two QTLs for seed cotton
      weight/plant and lint index and three QTLs for seed index were consistently
      detected both in F2 and F(2:3). Most QTLs for fiber qualities and yields were
      located at the same interval or neighboring intervals. These results indicated
      that the negative correlation between fiber qualities and yield traits may result
      from either pleiotropic effect of one gene or linkage effects of multiple closely
      linked genes.

PMID- 19103432
TI  - Reliability of assessing upper limb postures among workers performing
      manufacturing tasks.
AB  - The purpose of this study was to determine the inter- and intra-rater reliability
      of assessing upper limb postures of workers performing manufacturing tasks.
      Assessment of neck, shoulder, and wrist postures of 20 manufacturing employees
      was conducted by two raters observing digital video files using Multimedia Video
      Task Analysis (MVTA). Generalizability theory was used to estimate the inter- and
      intra-rater reliability. The results demonstrated good to excellent inter-rater
      reliability for neck and shoulder postures and fair to excellent inter-rater
      reliability for wrist postures. Intra-rater posture assessment demonstrated good
      to excellent reliability for both raters in all postures of the neck, shoulder,
      and wrist. This study demonstrated that posture assessment of manufacturing
      workers using MVTA is a reliable method.

PMID- 19103433
TI  - Self-regulation of unattainable goals in suicide attempters: the relationship
      between goal disengagement, goal reengagement and suicidal ideation.
AB  - There is growing interest in models of adaptive self-regulation. Recent research
      suggests that goal disengagement and goal reengagement (i.e., goal adjustment)
      are implicated in the self-regulation of emotion. This study extends the self
      regulation research to investigate the utility of goal adjustment in
      understanding suicidal risk. To this end, two hundred adults hospitalised
      following a suicidal episode completed a range of clinical and psychological
      measures in hospital and were followed up approximately 2.5 months after
      discharge (Time 2). Hierarchical regression analyses showed that goal
      reengagement predicted suicidal ideation at Time 2. In addition, the lack of goal
      reengagement was especially pernicious when reported concomitantly with high
      disengagement. These predictive effects were independent of baseline mood,
      attempt status and suicidal intent. The theoretical and clinical implications are
      discussed.

PMID- 19103434
TI  - The role of cystine-glutamate exchange in nicotine dependence in rats and humans.
AB  - BACKGROUND: The present study determined if, akin to cocaine, nicotine self
      administration in rats induces adaptations in the expression of glutamate
      transporters and cystine-glutamate exchangers in brain nuclei implicated in
      reinforcement and if treating cigarette smokers with a drug that restores cystine
      glutamate exchange affects the number of cigarettes smoked. METHODS: Rats self
      administered nicotine intravenously for 12 hours/day or received nicotine through
      osmotic minipumps for 21 days. Somatic signs of withdrawal were measured and
      immunoblotting was performed 12 hours after the last nicotine exposure to
      determine if the catalytic subunit of the cystine-glutamate exchanger, xCT, or
      the glial glutamate transporter, GLT-1, were altered in the ventral tegmental
      area (VTA), nucleus accumbens, prefrontal cortex, or amygdala. For the smoking
      reduction study in humans, nicotine-dependent smokers were treated for 4 weeks
      with N-acetylcysteine (2400 mg daily) to promote cystine-glutamate exchange or
      placebo. Participants provided weekly ratings of withdrawal symptoms, craving,
      and carbon monoxide (CO) measurements and logged daily cigarette and alcohol use.
      RESULTS: Rats receiving nicotine via self-administration or minipumps displayed
      somatic signs of withdrawal, but only nicotine self-administering rats showed
      decreased xCT expression in the nucleus accumbens and VTA and decreased GLT-1
      expression in the nucleus accumbens. Human smokers treated with N-acetylcysteine
      reported a reduction in cigarettes smoked, and there was no effect of N
      acetylcysteine on estimates of CO levels, craving, or withdrawal. CONCLUSIONS:
      These results indicate that the cystine-glutamate exchanger and the glial
      glutamate transporter are downregulated after nicotine self-administration, and
      augmenting exchanger activity with N-acetylcysteine reduced the number of
      cigarettes smoked in nicotine-dependent individuals.

PMID- 19103435
TI  - An exploration of the effect of modafinil on olanzapine associated weight gain in
      normal human subjects.
AB  - BACKGROUND: Weight gain has been associated with many second generation
      antipsychotics (SGAs). A variety of theories have been put forward as to the
      etiology of SGA-associated weight gain. Modafinil possesses pharmacologic effects
      that could influence the weight gain associated with SGAs. The objective of this
      trial was to determine the effect of modafinil on olanzapine-associated weight
      gain. METHODS: This study was a 3-week, randomized, double-blind, placebo
      controlled trial. All subjects received olanzapine titrated to 10 mg/day.
      Concurrently, subjects were randomized to receive modafinil titrated to 200
      mg/day or placebo. Weight and feeding lab assessments were conducted at baseline
      and endpoint. RESULTS: Fifty subjects were enrolled in the study with 20 subjects
      per group completing the trial. The primary outcome variable was change in the
      body mass index (BMI) over the 3 weeks of the trial. Increases in BMI were
      observed in both groups. However, analysis of covariance, controlled for baseline
      BMI, revealed that the olanzapine/placebo group had a greater increase in BMI at
      end point compared with the olanzapine/modafinil group (.89 +/- .59 vs. .47 +/-
      .50 kg/m(2), p < .05). When controlled for gender, the comparison showed a
      significant difference between groups at week 1 but not at weeks 2 or 3.
      CONCLUSIONS: The results of this trial should not be extrapolated to clinical
      practice at this time. These data do serve to support further evaluation in a
      patient population to determine if the weight modifying effect of modafinil can
      be demonstrated over a longer period of time.

PMID- 19103436
TI  - Degradation of association and projection white matter systems in alcoholism
      detected with quantitative fiber tracking.
AB  - BACKGROUND: Excessive alcohol use can cause macrostructural tissue shrinkage with
      regional preference for frontal systems. The extent and locus of alcoholism's
      effect on white matter microstructure is less known. METHODS: Quantitative fiber
      tracking derived from diffusion tensor imaging (DTI) assessed the integrity of
      samples of 11 major white matter bundles in 87 alcoholics (59 men, 28 women) and
      88 healthy control subjects (42 men, 46 women). Fiber integrity was expressed as
      fractional anisotropy (FA) and apparent diffusion coefficient (ADC), quantified
      separately for longitudinal diffusivity (lambdaL), a putative index of axonal
      integrity, and transverse diffusivity (lambdaT), a putative index of myelin
      integrity. RESULTS: Alcoholism affected FA and diffusivity, particularly lambdaT,
      of several fiber bundles. Frontal and superior sites (frontal forceps, internal
      and external capsules, fornix, and superior cingulate and longitudinal fasciculi)
      showed greatest abnormalities in alcoholics relative to control subjects. More
      posterior and inferior bundles were relatively spared. Lifetime alcohol
      consumption correlated with regional DTI measures in alcoholic men but not women.
      When matched for alcohol exposure, alcoholic women showed more DTI signs of white
      matter degradation than alcoholic men in several fiber bundles. Among all
      alcoholics, poorer performance on speeded tests correlated with DTI signs of
      regional white matter degradation. CONCLUSIONS: This survey of multiple brain
      fiber systems revealed a differential pattern of alcoholism's effect on regional
      FA and diffusivity with functional consequences attributable in part to
      compromised fiber microstructure with prominence in signs of myelin degradation.
      Sex-based differences suggest that women are at enhanced risk for alcoholism
      related degradation in selective white matter systems.

PMID- 19103438
TI  - Complexity analysis of spontaneous brain activity in attention
      deficit/hyperactivity disorder: diagnostic implications.
AB  - BACKGROUND: Attention-deficit/hyperactivity disorder (ADHD) is defined as the
      most common neurobehavioral disorder of childhood, but an objective diagnostic
      test is not available yet to date. Neurophychological, neuroimaging, and
      neurophysiological research offer ample evidence of brain and behavioral
      dysfunctions in ADHD, but these findings have not been useful as a diagnostic
      test. METHODS: Whole-head magnetoencephalographic recordings were obtained from
      14 diagnosed ADHD patients and 14 healthy children during resting conditions.
      Lempel-Ziv complexity (LZC) values were obtained for each channel and child and
      averaged in five sensor groups: anterior, central, left lateral, right lateral,
      and posterior. RESULTS: Lempel-Ziv complexity scores were significantly higher in
      control subjects, with the maximum value in anterior region. Combining age and
      anterior complexity values allowed the correct classification of ADHD patients
      and control subjects with a 93% sensitivity and 79% specificity. Control subjects
      showed an age-related monotonic increase of LZC scores in all sensor groups,
      while children with ADHD exhibited a nonsignificant tendency toward decreased LZC
      scores. The age-related divergence resulted in a 100% specificity in children
      older than 9 years. CONCLUSIONS: Results support the role of a frontal
      hypoactivity in the diagnosis of ADHD. Moreover, the age-related divergence of
      complexity scores between ADHD patients and control subjects might reflect
      distinctive developmental trajectories. This interpretation of our results is in
      agreement with recent investigations reporting a delay of cortical maturation in
      the prefrontal cortex.

PMID- 19103437
TI  - Divergent effects of genetic variation in endocannabinoid signaling on human
      threat- and reward-related brain function.
AB  - BACKGROUND: Fatty acid amide hydrolase (FAAH) is a key enzyme in regulating
      endocannabinoid (eCB) signaling. A common single nucleotide polymorphism (C385A)
      in the human FAAH gene has been associated with increased risk for addiction and
      obesity. METHODS: Using imaging genetics in 82 healthy adult volunteers, we
      examined the effects of FAAH C385A on threat- and reward-related human brain
      function. RESULTS: Carriers of FAAH 385A, associated with reduced enzyme and
      possibly increased eCB signaling, had decreased threat-related amygdala
      reactivity but increased reward-related ventral striatal reactivity in comparison
      with C385 homozygotes. Similarly divergent effects of FAAH C385A genotype were
      manifest at the level of brain-behavior relationships. The 385A carriers showed
      decreased correlation between amygdala reactivity and trait anxiety but increased
      correlation between ventral striatal reactivity and delay discounting, an index
      of impulsivity. CONCLUSIONS: Our results parallel pharmacologic and genetic
      dissection of eCB signaling, are consistent with the psychotropic effects of
      Delta(9)-tetrahydrocannabinol, and highlight specific neural mechanisms through
      which variability in eCB signaling impacts complex behavioral processes related
      to risk for addiction and obesity.

PMID- 19103439
TI  - Elevated cerebrospinal fluid lactate concentrations in patients with bipolar
      disorder and schizophrenia: implications for the mitochondrial dysfunction
      hypothesis.
AB  - BACKGROUND: Evidence is accumulating that mitochondrial dysfunction is involved
      in the pathophysiology of bipolar disorder and schizophrenia. Cerebrospinal fluid
      (CSF) concentration of lactate, a product of extra-mitochondrial glucose
      metabolism, is commonly elevated in individuals with mitochondrial disorders,
      especially those with neuropsychiatric symptoms. We tested the hypothesis that
      patients with bipolar disorder and schizophrenia would, on average, have elevated
      CSF lactate concentrations compared with healthy control subjects. METHODS: The
      CSF lactate and CSF and plasma glucose concentrations were measured with a YSI
      (YSI, Yellow Springs, Ohio) 2300 STAT Plus Glucose & Lactate Analyzer in 15
      samples from each of three groups of subjects: bipolar I disorder patients,
      schizophrenic patients, and healthy control subjects. RESULTS: Mean CSF lactate
      concentrations were significantly higher in bipolar (1.76 +/- .38) and
      schizophrenic subjects (1.61 +/- .31) compared with control subjects (1.31 +/-
      .21 mmol/L). These differences persisted after adjusting means for CSF glucose
      concentration, which correlated positively with CSF lactate concentration.
      CONCLUSIONS: This is the first report of increased CSF lactate concentrations in
      patients with bipolar disorder and schizophrenia. Elevated CSF lactate indicates
      increased extra-mitochondrial and anaerobic glucose metabolism and is consistent
      with impaired mitochondrial metabolism. Measuring CSF lactate concentration might
      help identify bipolar and schizophrenic patients with mitochondrial dysfunction
      who might benefit from research to elucidate and ultimately rectify possible
      mitochondrial pathology underlying these disorders.

PMID- 19103440
TI  - A new pathophysiological aspect of S100B in schizophrenia: potential regulation
      of S100B by its scavenger soluble RAGE.
AB  - BACKGROUND: Several studies have reported elevated S100B serum levels in
      schizophrenia. Our study focused on its scavenger, soluble receptor for advanced
      glycation end products (sRAGE). Given the benefits of sRAGE in metabolic and
      inflammatory diseases, we hypothesized a similar effect in schizophrenia.
      METHODS: S100B and sRAGE concentrations were explored during acute paranoid
      schizophrenia and during reconvalescence. Serum samples from 26 inpatients were
      investigated on hospital admission (T0) and 6 weeks posttreatment (T6) by S100B
      immunoluminometry and sRAGE-ELISA. Thirty-two matched healthy individuals served
      as controls. Psychopathology was monitored using the Positive and Negative
      Syndrome Scale (PANSS). RESULTS: S100B (p = .021) and sRAGE (p = .020) were
      elevated in schizophrenic patients at T0. S100B levels normalized under
      antipsychotic treatment (p = .003), whereas sRAGE increased further by T6 (p =
      .005). Changes of S100B during treatment correlated inversely with DeltasRAGE (r
      = -.422, p = .032). PANSS was negatively associated with sRAGE at T0 (positive
      score: r = -.415, p = .035; total score: r = -.395, p = .046). CONCLUSIONS: Our
      results provide support for a reduction of S100B levels during reconvalescence
      from acute paranoid schizophrenia that is regulated by its scavenger sRAGE. This
      mechanism could provide novel treatment strategies.

PMID- 19103441
TI  - What is an "adverse" environment? Interactions of rearing experiences and MAOA
      genotype in rhesus monkeys.
AB  - BACKGROUND: Studies have been inconsistent in demonstrating that early adversity
      and specific genotype can be joint risk factors for poor behavioral outcomes.
      Using a rhesus monkey model, we examined how social context and different forms
      of early adversity influence whether a specific genotype (polymorphism in the
      promoter region of monoamine oxidase A [MAOA]) affects display of aggressive,
      fearful, and anxious behaviors. METHODS: Rhesus monkey infants (n = 473) were
      exposed to brief social challenge at age 3-4 months. Infants were reared 1) with
      mothers and up to 150 other animals in large cages; 2) with mothers in smaller
      social groups; 3) with mother and access to, at most, one other mother-infant
      pair; and 4) without mother but with access to a same-age peer in a nursery.
      RESULTS: No effects of genotype were found for infants reared by mothers in large
      social cages, although several genotype by rearing environment interactions were
      evident. Animals reared in smaller social groups were more likely to display
      aggression, which was especially true of animals possessing the low-activity MAOA
      genotype. In addition, animals with low-activity genotypes that had experienced
      restricted mother rearing showed more anxious behavior (scratch, yawn).
      CONCLUSIONS: Among mother-reared animals, broader contextual features, associated
      with the social environment and experience of the mother, can affect the extent
      to which genotype contributes to behavioral expression under conditions of
      challenge. Results also suggest that different forms of early adverse experience
      can affect the types of responses displayed by animals of different genotypes.

PMID- 19103442
TI  - Delineation of two genetic pathways to major depression.
AB  - BACKGROUND: We sought to identify two sets of familial/genetic risk factors for
      major depression (MD): 1) high familial loading for MD, which we predicted would
      be most prominent in cases of MD with an early age at onset (AAO), and 2) high
      familial loading for vascular disease (VD), which should be strongest in MD cases
      with a late AAO. METHODS: We examined 4785 twin pairs from the Swedish Twin
      Registry, assessed at a mean age of 54.0 (SD = 7.4), where both members of the
      pair were evaluated by interview and at least one member reported a lifetime
      history of modified DSM-IV MD. Risk for VD was assessed from hospital discharge
      information and death certificates. RESULTS: Using Cox proportional hazard models
      and controlling for zygosity, age, and sex, early AAO in depressed twins
      predicted risk for MD in their cotwins, whereas late AAO predicted cotwin risk
      for VD. Using piecewise regression, the hazard ratio (HR) relating AAO per decade
      to risk for MD in cotwin was much stronger for AAO from 13-23 years (HR = .62)
      than for AAO 24-65 years (HR = 0.94). The HR relating AAO of MD in twin and risk
      for VD in cotwin was twice as strong for AAO from 47-65 years (HR = 1.17) as for
      AAO 13-46 years (1.08). CONCLUSIONS: From a familial/genetic perspective, MD is
      etiologically heterogeneous. Early and late onset MD are indexed, respectively,
      by the risk for MD and VD in relatives.

PMID- 19103443
TI  - Methylphenidate restores link between stop-signal sensory impact and successful
      stopping in adults with attention-deficit/hyperactivity disorder.
AB  - BACKGROUND: The ability to revise one's action plans, as reflected in so-called
      stopping performance, is of fundamental importance to adaptive behavior. Previous
      studies in children and adults with attention-deficit/hyperactivity disorder
      (ADHD) have revealed impaired stopping, which improved after the administration
      of methylphenidate (MPH). Event-related brain potentials revealed that one
      crucial mechanism in adequate stopping is the link between the cortical areas
      that process the signal to stop and the motor system (stop N1). This stop N1 was
      severely compromised in adults with ADHD. The present study investigates whether
      methylphenidate can restore the stop N1, in addition to improving stopping
      performance. The acute effect of a serotonergic reuptake inhibition on these
      parameters was also assessed. METHODS: Twelve adult combined-type ADHD patients
      received either placebo, MPH .4 mg/kg or .6 mg/kg, or 20 mg paroxetine in a
      double-blind, randomized, within-subjects design. RESULTS: The .6 mg/kg dose of
      methylphenidate improved stopping performance, whereas it did not affect go
      reaction time (RT). It also restored the stop N1 that was absent under placebo.
      Methylphenidate reduced a later stop-related potential, the stop P3, which may
      reflect monitoring of failed stops. Paroxetine had no effect on stopping
      performance or on stop N1, but it reduced stop P3. CONCLUSIONS: A .6 mg/kg dose
      of methylphenidate improves stopping performance and directly targets a stop
      related brain mechanism that has been reported before to be compromised in a
      group of ADHD patients. This mechanism was not influenced by acute serotonergic
      reuptake inhibition.

PMID- 19103444
TI  - Are the same phoneme and lexical layers used in speech production and
      comprehension? A case-series test of model of aphasic speech production.
AB  - In this paper, we investigate the claim that although the same lexical units are
      involved in speech production and comprehension, there are separate input and
      output phoneme layers (Foygel and Dell, 2000). Data from a case series of aphasic
      patients are used to test this claim by examining the relationship between
      performance on a test of picture naming and performance on tests of phonological
      input. Estimates of each patient's semantic-lexical and phonological impairments
      in speech production were derived from Foygel and Dell's computational model of
      picture naming. It was found that the strength of the semantic-lexical
      impairments in speech production was significantly correlated with performance on
      auditory comprehension tests. This finding is consistent with the claim that the
      same lexical units are involved in speech comprehension and production.
      Conversely, the correlations between the strength of the phonological lesions in
      speech production and performance on tests of phonological input were non
      significant, consistent with Foygel and Dell's claim that there are distinct
      input and output phoneme layers.

PMID- 19103445
TI  - Integration of lexical and sublexical processing in the spelling of regular
      words: a multiple single-case study in Italian dysgraphic patients.
AB  - In this study we investigated 12 cases of "mixed dysgraphia", a spelling
      impairment where regular words are spelt better than either ambiguous words or
      regular non-words. Two explanations of mixed dysgraphia were formerly offered by
      Luzzatti et al. (1998): (i) a double functional lesion of the orthographic output
      lexicon (or damage to its access) and of the acoustic-to-phonological conversion;
      and (ii) some kind of interaction/summation between lexical and sublexical
      spelling routes when processing regular words. We first analysed whether a double
      functional lesion was sufficient to explain the mixed dysgraphia, checking
      acoustic-to-phonological conversion by means of the repetition of words and non
      words: the answer was positive in five cases and uncertain in three. We tested
      the remaining four cases to see if there was an interaction between lexical and
      sublexical processing of regular words, quantifying for each patient, on a
      probabilistic basis, the separate contribution of the residual lexical and
      sublexical resources. We investigated whether the processing along these routes
      was simultaneous but independent ("independent cooperation") or if instead there
      was "interaction", i.e., the simultaneous activity led to an added increase of
      efficiency over and above the mere combination of separate success probabilities.
      For one case the processing along the two routes was independent, in the other
      three cases an interaction resulted. Following the same approach, we found that
      for the five cases with a double functional lesion, the observed success on
      regular word spelling was higher than that expected on a probabilistic basis, but
      the interpretation of this finding was different.

PMID- 19103446
TI  - Electrophysiological correlates of different anomic patterns in comparison with
      normal word production.
AB  - Different forms of anomia are observed in aphasia, which can be related to
      impaired semantic, lexical or phonological processes. In the present study, we
      analysed electrophysiological correlates of different patterns of anomia in six
      aphasic speakers. Event-related potentials (ERPs) were recorded during picture
      naming in each anomic speaker and in 15 healthy controls. Waveform analysis and
      temporal segmentation indicated a difference between high and low frequency words
      in the control group between 270 and 330 msec after picture onset. The ERPs
      recorded in the patients were compared to the control group. The time-windows of
      divergent ERP correlates were very similar between successful and erroneous
      naming, but they were differently distributed in the 6 patients. Two patients
      with conduction aphasia and impaired phonological encoding had normal electro
      cortical activity during the first 300 msec and abnormal patterns between 300 and
      450 msec. Two patients with lexical-semantic impairment had earlier ERP
      abnormalities starting immediately after visual processes. The two patients with
      less severe anomia and preponderance of omission errors displayed abnormal ERPs
      between 280 and 350 msec. These results indicate that abnormal electro-cortical
      correlates of anomic profiles can be observed in different time-windows, which
      seem to correspond to the time course of the impaired encoding processes.

PMID- 19103447
TI  - The use and misuse of neuroscience in education.

PMID- 19103448
TI  - Epidermoid cyst causing clitoromegaly in a child.

PMID- 19103449
TI  - Emotional Lability in MND: Relationship to cognition and psychopathology and
      impact on caregivers.
AB  - Emotional Lability (EL) is a well recognized symptom of cortico-bulbar pathway
      dysfunction in Motor Neuron Disease/Amyotrophic Lateral Sclerosis (MND/ALS), and
      is reported to occur in 19-49% of patients. The Emotional Lability Questionnaire
      (ELQ), is specifically designed to detect EL as reported by MND patients and as
      observed by their carers. The aims of this study were to 1) validate the Italian
      version of the ELQ; 2) investigate the relationship between EL and presence of
      cognitive dysfunction; 3) investigate the relationship between EL and presence of
      psychopathology. Forty one MND patients, 39 caregivers and respective control
      groups composed of 39 subjects and 39 partners/friends were tested. The Italian
      version of the ELQ was found to have good psychometric properties. Seventy-one
      per cent of patients reported suffering from EL. Correlations were found between
      bulbar involvement and EL, and between bulbar involvement and low performance on
      tests of fluid intelligence and working memory. However, the cognitive profile
      did not correlate with any aspect of EL. The findings suggests that damage to
      different neurological pathways underlie cognitive change and EL, which supports
      the concept of MND/ALS as a multisystem disorder. Moreover the outcomes suggest
      that EL affects patients' everyday life with the increased anxiety and emotional
      frailty. The findings suggest that those involved in the care of MND patients
      should be more aware of the effects of EL in the management of the disease.

PMID- 19103450
TI  - Infectious aneurysm of the intracavernous carotid artery occurring concomitantly
      with sphenoid sinusitis; an autopsy case report.
AB  - A previously healthy 56-year-old woman presented with right-sided ophthalmic pain
      and diplopia following headache and fever. A neurological examination revealed
      3rd and 6th right cranial nerve palsies. Brain magnetic resonance imaging (MRI)
      and 3D-computed tomography (CT) angiography (CTA) showed right-sided sphenoid
      sinusitis, cavernous sinus thrombophlebitis, and aneurysms in the right
      intracavernous carotid artery and in a portion of internal carotid-posterior
      communicating artery. We diagnosed her condition as cavernous sinus syndrome with
      an infectious aneurysm secondary to sphenoiditis; therefore, broad spectrum
      antibiotics were administered. However, 7 days after admission, she died of
      massive epistaxis. Macroscopically, coagulated blood was observed at the surface
      of the sphenoid sinus, suggesting bleeding in the cavernous sinus. A
      histopathological examination revealed severe infiltration of the inflammatory
      cells into the cavernous sinus and sphenoid mucosa. Rupture of the aneurysm in
      the cavernous sinus was also observed. However, no pathogenic organism was
      identified. We thought that the sphenoid sinusitis had spread through the venous
      flow into the cavernous, and the infectious aneurysm developed due to
      infiltration of inflammatory cells into the arterial wall. This is the first
      detailed clinico-pathological study of an infectious aneurysm in the
      intracavernous internal carotid artery occurring concomitantly with sphenoiditis.

PMID- 19103451
TI  - The activity and expression of chitinase in the equine lung and its activity in
      normal horses and animals with recurrent airway obstruction.
AB  - Recurrent airway obstruction (RAO) is a chronic inflammatory condition in equine
      lung, which may share a common immunological basis with human asthma, in which
      dysregulated Th2 responses occur. Mammals express chitinases and chitinase-like
      proteins, two of which are active enzymes, chitotriosidase and acidic mammalian
      chitinase (AMCase). Both enzymes are upregulated in a range of inflammatory
      conditions, including asthma. We investigated the activity of chitinase in
      bronchoalveolar lavage fluid from horses with and without RAO in response to
      organic dust challenges. No significant differences were found in activity,
      although in one study RAO animals had elevated chitinase activity that fell short
      of statistical significance. The pH optimum and pH lability of the activity was
      consistent with the presence of chitotriosidase. RT-PCR amplification of the mRNA
      encoding chitotriosidase and AMCase in normal equine lung showed that
      chitotriosidase, but not AMCase, is expressed in trachea, bronchi, and peripheral
      lung tissue. The gene for chitotriosidase was identified from the Equus caballus
      (horse) genome 1.1 database and its similarity to the same genes from other
      species was determined. The results of this study indicate that the involvement
      of chitotriosidase in RAO is uncertain.

PMID- 19103452
TI  - Partitioning of chlorpyrifos to soil and plants in vegetated agricultural
      drainage ditches.
AB  - Constructed wetlands and vegetated agricultural drainage ditches (VADD) have been
      proposed as structural best management practices for the mitigation of
      chlorpyrifos contamination in agriculturally dominated watersheds. Sorption to
      soil and submergent aquatic plants has been measured as an important sink for
      chlorpyrifos; however, sorption to emergent plants has not been well
      characterized. Sorption isotherms for two soils and five emergent plants were
      determined by batch equilibrium technique. Sorption to whole plant stems
      (K(d)=570-1300 L kg(-1)) was more than 10 times higher than to soil (K(d)=40-71 L
      kg(-1)). Chopped plant material had K(d) values 7.6-96.2% greater than whole
      stems. Wetland plants with high internal surface area due to porous tissues had
      greater linear partitioning coefficients than terrestrial plants with a hollow
      structure. Chlorpyrifos sorption reached pseudo-equilibrium rapidly, indicating
      that partitioning will be an important mechanism in vegetated natural treatment
      systems for mitigating peak concentrations in surface waters and allowing time
      for attenuation by slower degradation reactions.

PMID- 19103453
TI  - Sorption characteristics of pesticides on matrix substrates used in
      biopurification systems.
AB  - On-farm biopurification systems were developed to remove pesticides from
      contaminated water generated at the farmyard. An important process in the
      system's efficiency is the sorption of pesticides to the substrates used in the
      biopurification systems. The composition and type of material present in the
      biobed are crucial for retention of chemicals. This study investigated the
      sorption of linuron, isoproturon, metalaxyl, isoxaben, bentazon and lenacil on
      substrates commonly used in a biopurification system, i.e. cow manure, straw,
      willow chopping, soil, coconut chips, garden waste compost, and peat mix. Linear,
      Freundlich, and Langmuir sorption isotherms were fitted to the obtained data. The
      best fit was obtained with the Freundlich model. More immobile pesticides (i.e.
      linuron and isoxaben) tended to associate with the organic substrate, while more
      mobile pesticides partition in the water (i.e. bentazon). According to sorption
      capacity, the substrates could be classified as peat mix > compost, coco chips,
      straw > cow manure, willow chopping > sandy loam soil. Sorption capacity was
      positively correlated with the organic carbon content, CaO and the cation
      exchange capacity. Furthermore, no significant differences in sorption could be
      found between technical and formulated isoproturon and bentazon. Moreover, the
      individual sorption coefficient K(d) was additive, which means that individual
      sorption coefficients can be used to calculate the sorption coefficients of a
      mixture of substrates. What concerns the mutual interaction of pesticides it
      could be observed that the sorption of linuron and metalaxyl was significantly
      lower in combination with isoproturon and bentazon, while the latter pesticides
      were not influenced by the presence of linuron and metalaxyl. As guidelines,
      firstly, it could be stated that using the most sorbing materials such as peat
      mix, might significantly increase the biopurification systems efficiency.
      Secondly, the treatment of very mobile pesticides, such as bentazon, should be
      taken with care as these will easily leach through the system. Additional
      chemical treatment might be necessary for these type of pesticides.

PMID- 19103455
TI  - Some organochlorine pesticide residues in fish species in Konya, Turkey.
AB  - The levels of organochlorine pesticides were measured in 18 fish species from
      Konya markets, Turkey. These species were selected on the basis of their
      importance to local human fish consumption. The extracted residues were analyzed
      on a micro capillary gas chromatograph equipped with an electron capture
      detector. Total 14 different organochlorine pesticides were determined. These
      residues were detected in all fish species, except in trout, horse mackerel and
      bonito. DDT and its metabolites and HCH were the predominant contaminants in fish
      muscles. The mean concentrations of summation operator DDT were in the range
      between 0.0008 and 0.0828 microg g(-1). DDT was the predominant residue in Sparus
      aurata. Detectable levels of HCH, aldrin, and heptachlor were found in most
      samples. However, dieldrin, endrin, beta endosulfan, p-p' DDT, and p-p' DDD were
      not found in Salmo trutta. The mean of endrin ranged from 0.0040 microg g(-1)
      (Triglia lineate) to 0.0326 microg g(-1) (Trachurus trachurus). These results
      give no indication of important health risks associated with the consumption of
      these fishes in Konya markets.

PMID- 19103454
TI  - Study on the raw fish oil purification from PCDD/F and dl-PCB-industrial tests.
AB  - The results of tests for the purification of fish oils with activated carbon for
      industrial use are presented. The optimum parameters for the process of
      purification (granulation of the activated carbon, its dosage, the oil
      temperature, and the duration of mixing the oil with activated carbon) were
      previously established for the laboratory scale. The optimization of the process
      consisted of selecting purification parameters that would allow for maximum
      reduction of the toxic polychlorinated dibenzo-para-dioxins and polychlorinated
      dibenzofurans (PCDD/Fs) content, while retaining the favorable high fatty acid
      content [C20:5 n-3, eicosapentaenoic acid (EPA) and C22:6 n-3, docosahexaenoic
      acid (DHA)]. The use of that optimum parameters in industrial conditions
      confirmed the satisfactory results obtained in laboratory tests. Five types of
      oil derived from various Baltic fish were purified. Reduction in the PCDD/Fs
      content was 77.0-93.6% on average, whereas in the dioxin-like polychlorinated
      biphenyls (dl-PCBs)-it was 42.7-50.5% on average, with insignificant changes in
      the total amount of EPA and DHA content. Furthermore, a significant reduction in
      the content of arsenic was noted (by about 62% on average), with insignificant
      changes in the content of organochlorine pesticides (OCPs), and marker
      polychlorinated biphenyls (PCBs), polybrominated diphenyl ethers (PBDEs),
      cadmium, lead, and mercury. Purification provided fish oil having standardized
      parameters that allow for its use as feed additives, whilst retaining its
      favorable fatty acid content.

PMID- 19103456
TI  - The potential of oil-utilizing bacterial consortia associated with legume root
      nodules for cleaning oily soils.
AB  - The surfaces of root nodules of Vicia faba and Lupinus albus (legume crops), were
      colonized with bacterial consortia which utilized oil and fixed nitrogen. Such
      combined activities apparently make those periphytic consortia efficient
      contributors to bioremediation of oily nitrogen-poor desert soils. This was
      confirmed experimentally in this study. Thus, cultivating V. faba, L. albus and,
      for comparison, Solanum melongena, a nonlegume crop, separately in oily sand
      samples resulted in more oil attenuation than in an uncultivated sample. This
      effect was more pronounced with the legume crops than with the nonlegume crop.
      Furthermore, in flask cultures, V. faba plants with nodulated roots exhibited a
      higher potential for oil attenuation in the surrounding water than plants with
      nodule-free roots. Denaturation gradient gel electrophoresis (DGGE) of polymerase
      chain reaction amplified 16S rRNA coding genes revealed that periphytic bacteria
      had DGGE bands not matching those of the oil-utilizing rhizospheric bacteria.
      Legume nodules also contained endophytic bacteria whose 16S rDNA bands did not
      match those of Rhizobium nor those of all other individual periphytic and
      rhizospheric strains. It was concluded that legume crops host on their roots
      bacterial consortia with a satisfactory potential for oil phytoremediation.

PMID- 19103457
TI  - Laboratory toxicity test and post-exposure feeding inhibition using the giant
      freshwater prawn Macrobrachium rosenbergii.
AB  - A bioassay was developed using post-larvae of freshwater prawn Macrobrachium
      rosenbergii (length 9-10 mm) in order to determine the toxicity of profenofos,
      dimethoate, chlorpyrifos, carbendazim and zinc. This was the first study in the
      tropics with M. rosenbergii, particularly at the post-larvae stage (9-10 mm) on
      lethal (LC(50)) and sublethal (EC(50)) effects of toxic substances using post
      exposure feeding rate as end point. Median lethal concentrations (LC(50) at 24
      and 48 h) were respectively estimated as 11.6 and 9.8 microg L(-1) for
      profenofos, 142.1 and 102.7 microg L(-1) for dimethoate, 0.7 and 0.3 microg L(-1)
      for chlorpyrifos, and 439.7 and 329 microg L(-1) for zinc. Effects of carbendazim
      could not be estimated because carbendazim exposure needs more than 24h exposure
      period to produce observable effects at the concentrations used. The EC(50) using
      post-exposure feeding rates determined for profenofos, dimethoate, chlorpyrifos
      and zinc were 6.023, 269.3, 0.293 and 109.01 microg L(-1), respectively, at 24 h
      of exposure. Only chlorpyrifos and zinc had LC(50) concentrations greater than
      the post-exposure feeding EC(50) concentrations. This study demonstrated that the
      M. rosenbergii could also be used as a test animal to detect the effects of
      different chemical contaminants in aquatic environments.

PMID- 19103458
TI  - 2-Aminobenzothiazole degradation by free and Ca-alginate immobilized cells of
      Rhodococcus rhodochrous.
AB  - 2-Aminobenzothiazole (ABT) degradation was investigated using free and
      immobilized systems during photodegradation under solar light in the presence of
      Fe(III)-nitrilotriacetic acid (FeNTA), biodegradation by Rhodococcus rhodochrous,
      and during combined conditions. Ca-alginate hydrogel was chosen as a model matrix
      and some complementary studies were required to characterize this new system. R.
      rhodochrous metabolism in this type of environment was monitored by NMR
      spectroscopy. Neither change in intracellular pH values nor in ATP concentrations
      was observed by in vivo(31)P NMR, showing that no metabolic modification occurred
      between free and immobilized cells. (1)H NMR demonstrated that alginate was not
      used as carbon source by R. rhodochrous. After establishing the pre-treatment
      protocol by SPE to eliminate solubilised alginate, ABT adsorption on beads and
      degradation were studied. The same pathways of transformation were observed in
      suspended and immobilized cell systems. Considering the ABT adsorption phenomenon
      on alginate beads (8%), the efficiency of the two systems was found to be
      comparable although the degradation rate was slightly lower with immobilized
      cells. The most important result was the finding that the positive effect of
      FeNTA on ABT degradation with immobilized cells was similar to that observed
      previously with free cells. All these results show that mechanisms observed with
      free cells can be extrapolated to entrapped cells, i.e. under conditions much
      closer to those usually encountered in the environment.

PMID- 19103459
TI  - Characteristics, toxicity, and source apportionment of polycylic aromatic
      hydrocarbons (PAHs) in road dust of Ulsan, Korea.
AB  - This study identified concentrations, molecular distributions, toxicities, and
      sources of polycylic aromatic hydrocarbons (PAHs) in road dust from different
      areas of Ulsan, the largest industrial city in Korea. The total PAH
      concentrations in industrial areas were dependent on industrial emissions and
      vehicular exhaust, while those in urban areas were mainly dependent on traffic
      density, sampling site location, and accumulation of pollutants or road dust. The
      PAH concentration of each particle size group increased with decreasing particle
      size. This may be because of the higher surface area available for deposition or
      coating of PAHs in road dust with smaller particle sizes. The molecular
      distributions of PAHs among the sites in the petrochemical area and heavy traffic
      area were similar because of the similarities in their emission sources. The
      toxic equivalent concentrations (TEQs) of PAHs in the road dust ranged from 0.93
      microg/g to 16.74 microg/g in industrial areas and from 4.37 microg/g to 68.84
      microg/g in urban areas. The correlation coefficient of total PAH concentration
      and TEQ in urban areas was 0.98, which was much higher than that in industrial
      areas where it was 0.75. Principal component analysis showed that PAHs in road
      dust from Ulsan originate from four main sources: diesel vehicular emissions, oil
      combustion, gasoline vehicular emissions, and coal combustion.

PMID- 19103460
TI  - Dietary exposure and biomarkers of arsenic in consumers of fish and shellfish
      from France.
AB  - Seafood, especially fish, is considered as a major dietary source of arsenic
      (As). Seafood consumption is recommended for nutritional properties but
      contaminant exposure should be considered. The objectives were to assess As
      intake of frequent French seafood consumers and exposure via biomarkers.
      Consumptions of 996 high consumers (18 and over) of 4 coastal areas were assessed
      using a validated food frequency questionnaire. Seafood samples were collected
      according to a total diet study (TDS) sampling method and analyzed for total As,
      arsenite (AsIII), arsenate (AsV), arsenobetaine (AsB), monomethylarsonic acid
      (MMA) and dimethylarsinic acid (DMA). The average As dietary exposure is 94.7+/
      67.5 microg/kg bw/week in females and 77.3+/-54.6 microg/kg bw/week in males
      (p<0.001) and the inorganic As dietary exposure is respectively 3.34+/-2.06
      microg/kg bw/week and 3.04+/-1.86 microg/kg bw/week (p<0.05). Urine samples were
      collected from 382 of the subjects. The average urinary As concentration is
      94.8+/-250 microg/g creatinine for females and 59.7+/-81.8 microg/g for males
      (p<0.001). Samples having an As concentration above 75 microg/g creatinine
      (n=101) were analyzed for inorganic As (As(III), As(V), MMA(V) and DMA(V)) which
      was 24.6+/-27.9 microg/g creatinine for males and 27.1+/-20.6 microg/g for
      females. Analyses do not show any correlation between dietary exposure and
      urinary As. These results show that biological results should be interpreted
      cautiously. Diet recording seems to be the best way to assess dietary As
      exposure. Seafood is a high source of As exposure but even among high consumers
      it is not the main source of toxic As. From a public health point of view these
      results should be interpreted carefully in the absence of international consensus
      on the health-based guidance value.

PMID- 19103461
TI  - Effects of inosine on response to in vitro hypoxia in absence of substrate on
      bladder dysfunction in adult rats.
AB  - OBJECTIVES: To investigate the effects of inosine on in vitro ischemia
      reperfusion injury to urinary bladders in adult rats. Inosine has neuroprotective
      effects against cerebral and cardiac ischemia-reperfusion injury. METHODS: A
      total of 18 adult male rats were used. Each rat was anesthetized, and the bladder
      was excised, cut longitudinally into 3 equal strips, and mounted in individual
      baths. Six strips were run simultaneously. Inosine (37.3 mM) was added to the
      baths containing strips 2, 4, and 6. All strips were equilibrated for 1 hour in
      oxygenated Tyrode solution containing glucose and at the end of the hour were
      stimulated with field stimulation, carbachol, and KCl. Strips 1 and 2 were
      subjected to repetitive stimulation (RS) by field stimulation (32 Hz) every 5
      minutes for 1 hour; strips 3 and 4 were subjected to Tyrode equilibrated solution
      with nitrogen and no glucose for 1 hour; and strips 5 and 6 were subjected to in
      vitro hypoxia in the absence of substrate plus RS for 1 hour. All strips were
      then incubated in oxygenated Tyrode solution for 1 hour and stimulated as before.
      RESULTS: In normoxia, inosine had no beneficial effects either before or after
      RS. However, in the ischemic model, the bladder strips incubated with inosine
      showed significantly better contractile responses to stimulation with carbachol
      and KCl. After hypoxia without substrate plus RS, the strips incubated with
      inosine showed increased responses to all 3 forms of stimulation. CONCLUSIONS:
      Inosine protected the contractile responses of the bladder strips after in vitro
      hypoxia without substrate with or without RS.

PMID- 19103462
TI  - Polypharmacy prevalence rates in the treatment of unipolar depression in an
      outpatient clinic.
AB  - OBJECTIVE: Unipolar depression is a complex illness with an ever increasing
      number of pharmacological treatments available. As the number of available
      medication options increases, so does the potential for polypharmacy, a practice
      with possible complications. Such complications include a greater number of side
      effects with the initiation of additional medications and the consequences of
      drug-drug interactions. Therefore, it is important to understand the effects of
      polypharmacy on efficacy of treatment as well as whether polypharmacy is
      instituted after appropriate initial monotherapy trials. This study attempts to
      answer these questions. METHODS: Patient names for this investigation were
      provided by residents in the UMass Medical School Psychiatry Residency program.
      The charts of these patients were analyzed to collect data regarding
      demographics, clinical data about the illness, medication names, types, duration
      of use and to access efficacy using the Clinical Global Impression (CGI).
      RESULTS: Of 160 reviewed charts, 135 subjects were included in the final analyses
      (others excluded due to incomplete data or no depression diagnosis). Patients
      were on average on 2.0 medications (SD=0.5) with 2.1 past trials. A greater
      number of current antidepressant medications did not correlate with a greater
      improvement in CGI, implying that polypharmacy did not necessarily lead to
      greater efficacy. The impact of illness severity, as measured by comorbidities,
      substance abuse, and trauma history, were included in the analysis, and did not
      significantly change this outcome. Additionally, prescription patterns themselves
      were examined, including reasons for termination of medication trials, the impact
      of side-effects, and the number of patients that had complete monotherapy trials
      before transitioning to polypharmacy. STUDY LIMITATIONS: Small sample size,
      retrospective review, one CGI rater. CONCLUSIONS: First, many patients did not
      receive an adequate monotherapy trial, as defined by dose and duration, before
      progressing to polypharmacy. Secondly, the use of two or more medications
      concurrently did not appear to increase efficacy as measured by CGI. Due to study
      limitations, direct comparison of the efficacy of one and two medications was not
      significant; however the study did demonstrate a general correlation between
      polypharmacy and greater depressive symptomatology. This suggests the need for
      optimizing monotherapy regimens before initiating polypharmacy that may not lead
      to improvement in symptoms.

PMID- 19103463
TI  - Diagnostically irrelevant information can affect the likelihood of a diagnosis of
      bipolar disorder.
AB  - Bipolar disorders are misdiagnosed in many cases. We hypothesized that this
      occurs because therapists do not base their diagnostic decision solely on
      criteria set out by ICD-10 or DSM-IV. We expected that instead, patients offering
      a plausible causal explanation for their symptoms (i.e. having fallen in love)
      are less likely to be diagnosed as bipolar. In the same way we expected that
      patients who report decreased need for sleep are more likely to be diagnosed as
      bipolar than those who do not present with this additional symptom. We sent a
      case vignette describing a person with bipolar disorder to 400 psychotherapists.
      This vignette was varied with respect to these two pieces of information, but
      each case described included all necessary criteria to diagnose a bipolar
      disorder according to DSM-IV or ICD-10. This variation, along with the
      theoretical approach of the therapist affected the likelihood of a bipolar
      diagnosis.

PMID- 19103464
TI  - Decreased muscarinic receptor binding in the frontal cortex of bipolar disorder
      and major depressive disorder subjects.
AB  - BACKGROUND: Dysfunction of the cholinergic muscarinic receptors has been
      implicated in the pathology of bipolar disorder and major depressive disorder.
      However, there is conflicting evidence regarding the association between
      individual muscarinic receptors and the two disorders. METHODS: We used the
      muscarinic receptor selective radioligands [3H]pirenzepine, [3H]AFDX-384 and
      [3H]4-DAMP to measure the levels of muscarinic(1) (CHRM1) and muscarinic(4)
      (CHRM4) receptors, muscarinic(2) (CHRM2) and muscarinic(4) (CHRM4) receptors and
      muscarinic(3) (CHRM3) receptor, respectively. Radioligand binding was measured in
      Brodmann's area (BA) 10 of the rostral prefrontal cortex, BA 46 of the
      dorsolateral prefrontal cortex and BA 40 of the parietal cortex in the post
      mortem CNS from subjects with bipolar disorder or major depressive disorder and
      control subjects. RESULTS: [3H]AFDX-384 binding was decreased in BA 46 in both
      bipolar disorder (p<0.01) and major depressive disorder (p<0.05). [3H]4-DAMP
      binding was decreased in BA 10 in bipolar disorder (p<0.05) but not major
      depressive disorder (p>0.05). [3H]AFDX-384 and [3H]4-DAMP binding were unaltered
      in any other cortical region examined for either disorder (p>0.05).
      [3H]pirenzepine binding was not significantly altered in either disorder in any
      cortical region examined (p>0.05). LIMITATIONS: 9 bipolar disorder, 9 major
      depressive disorder and 19 control subjects were used in the study. CONCLUSION:
      Our data is consistent with previously published data implicating a role for
      CHRM2 receptors in the pathology of bipolar and major depressive disorder. The
      demonstration of a novel association between decreased CHRM3 receptor expression
      and bipolar disorder suggests bipolar and major depressive disorder differs in
      the underlying nature of their cholinergic dysfunction.

PMID- 19103465
TI  - Alexithymia determines the anxiety experienced in skydiving.
AB  - BACKGROUND: High-risk activities have typically been explored within a sensation
      seeking framework. They may, however, allow those with emotional difficulties to
      experience and regulate their emotions. METHODS: Skydivers (n=87) completed
      anxiety and heart rate data four times on a single day before and after a
      skydive. RESULTS: A 2 (group: alexithymic; non alexithymic) x 4 (time) ANOVA with
      repeated measures on the second factor revealed a significant alexithymia x time
      interaction, F(2.27, 192.60)=45.48, p<.001, eta(2)=.35. Anxiety fluctuated
      significantly more for alexithymic skydivers than it did for their non
      alexithymic counterparts. This interaction was not mirrored by heart rate. The
      relationship between alexithymia and anxiety remained significant when accounting
      for sensation seeking. LIMITATIONS: The results leave open interpretations that
      are based on anhedonia, which was not controlled for. CONCLUSIONS: Alexithymic
      individuals may find, in the high-risk domain, an environment that satisfies
      their emotion regulation needs.

PMID- 19103466
TI  - Comments on "The relation between Helicobacter pylori infection and cardiac
      syndrome X: a preliminary study", Assadi M, et al.

PMID- 19103467
TI  - Improved isolation and detection of pathogenic Vibrio parahaemolyticus from
      seafood using a new enrichment broth.
AB  - The efficiency of a new enrichment broth containing bile salt, sodium
      taurocholate (ST broth) in detecting pathogenic Vibrio parahaemolyticus from
      seafood was compared with the traditional alkaline peptone water (APW). Both the
      enrichment broths were compared using 58 seafood samples harvested along the
      southwest coast of India using conventional isolation, colony hybridization
      following enrichment (CFE) and PCR. V. parahaemolyticus carrying tdh gene were
      isolated from 6.9% (4/58) and 3.4% (2/58) of the samples after enrichment in ST
      broth and APW, respectively. Pathogenic V. parahaemolyticus carrying trh gene
      were isolated from 20.7% (12/58) and 13.8% (8/58) of the samples after enrichment
      in ST broth and APW respectively. PCR using enrichment lysate as template could
      detect V. parahaemolyticus carrying tdh gene in 8 (13.8%) and 12 (20.7%) samples
      after enrichment in APW and ST broth, respectively. Positivity for trh gene based
      PCR was 24 (41.4%) for ST broth and 19 (32.8%) for APW. Total V. parahaemolyticus
      were detected and isolated from almost same number of samples using two
      enrichment broths by three methods used in this study. The results suggest that
      the ST broth is superior to APW for detection and isolation of pathogenic V.
      parahaemolyticus from seafood.

PMID- 19103468
TI  - Subject specific finite element analysis of stress shielding around a cementless
      femoral stem.
AB  - BACKGROUND: Stress shielding around a femoral stem is usually assessed
      experimentally using composite or human cadaver femurs. In the present study we
      have explored the feasibility of using subject specific finite element models to
      determine stress shielding in operated femurs. METHODS: Cortical strain was
      measured experimentally on seven human cadaver femurs, intact and implanted with
      a straight cementless prosthesis. Two load configurations were considered: single
      leg stance and stair climbing. Subject specific finite element models derived
      from computed tomography of the same femurs were analysed intact and with an
      implant. Principal cortical strain was used to validate the finite element
      models. Stress shielding was defined as the change in equivalent (von Mises)
      strain between pre- and post-operative femurs. FINDINGS: Cortical strain
      predicted by the finite element analyses showed to be close to unity with the
      experimental observations for both intact (R2=0.94, slope=0.99), operated femurs
      (R2=0.86, slope=0.86) and stress shielding (R2=0.70, slope=0.90). In the proximal
      calcar area, the region most prone to periprosthetic remodelling, the finite
      element models were found to successfully reproduce the stress shielding observed
      experimentally. INTERPRETATION: The study shows that subject specific finite
      element models manage to describe the stress shielding pattern measured in vitro
      in the different femurs. Finite element models based on actual human femurs
      (cadaver and/or patient) could thus be a useful tool in the pre-clinical
      evaluation of new implants.

PMID- 19103469
TI  - The resurgence of tuberculosis in the Republic of Ireland: perceptions and
      reality.
AB  - Tuberculosis remained a very significant cause of death in Ireland until the mid
      20th century and still occupies a prominent position in the folk memory. As I
      show with reference to recent Irish media coverage, the global resurgence of
      tuberculosis is therefore viewed with concern in Ireland. Using data collated by
      the Health Protection Surveillance Centre between 1998 and 2005 however, I show
      that the recent increase in tuberculosis incidence in Ireland is less than is
      popularly perceived. This increase is largely associated with economic immigrants
      attracted to Ireland by the 'Celtic Tiger' economic boom, but there is little
      evidence to suggest that this has had a negative impact on the Irish-born
      population. Drug resistance is still a small but growing problem. Whilst
      vigilance is required, it is argued that the recent increase does not at present
      indicate a likely return to the situation in the mid-20th century.

PMID- 19103470
TI  - Theoretical examination of aggregation effect on the dielectric characteristics
      of spherical cellular suspension.
AB  - Dielectric dispersion analysis of cellular suspension is generally based on the
      analogy to equivalent periodic material made up of identical inclusions. However,
      under true physiological conditions, when coupling and aggregation events usually
      occur, this analogy can introduce severe errors when attempting to probe the
      dielectric characteristics of the suspended fraction. In the framework of this
      study, a theoretical examination of the effect of aggregation on the dielectric
      characteristics of spherical cellular suspension is presented. Here, small
      clusters of coupled and fused (gap connected) shelled spheres were used to
      imitate the presence of aggregates when suspended in a homogenous suspension of
      spherical cells. The permittivity spectra of the aggregate-cell mixtures were
      numerically calculated by applying computational solution of complex potential
      problem using 3D Boundary Element Method. The dispersion characteristics of the
      mixtures have been determined as function of both aggregates shape and
      concentration. Those reveal significant deviations in comparison to the
      characteristics of homogenous cellular suspension. Quantitative analyses of the
      induced fields and transmembrane potential gradients of the interacted cells
      suggest that those deviations are mainly induced due to changes occur on the
      polarization state of the membranes.

PMID- 19103471
TI  - HDAC expression and clinical prognosis in human malignancies.
AB  - Histone deacetylases are known to play a central role in the regulation of
      several cellular properties intimately interlinked with the development and
      progression of cancer. Consequently, a multitude of histone deacetylase (HDAC)
      inhibitors have been developed and are currently tested as anticancer agents in a
      variety of solid and hematologic malignancies. However, only recently research
      began to focus on the actual expression patterns of specific HDAC isoforms in
      neoplasias. The majority of studies investigating this issue reported an enhanced
      expression of class I HDAC isoforms in solid human tumours, both on mRNA and
      protein level, when compared to the respective tissue of origin. In most studies,
      class I HDAC expression was high in locally advanced, dedifferentiated, strongly
      proliferating tumours. In some but not all entities elevated class I HDAC
      expression was associated with compromised patient prognosis, however, an
      association of elevated class I HDAC expression with improved prognosis has also
      be reported for selected tumour entities. In contrast to class I isoforms,
      expression of class II HDACs has been found reduced in tumours and high
      expression of these isoforms in some entities predicted better patient outcome.
      Since all of these data point to a potential biological role of differences in
      HDAC expression in human tumours, future translational studies will focus on the
      question, whether HDAC expression patterns are predictive for response to
      treatment with histone deacetylase inhibitors.

PMID- 19103473
TI  - Oxidative stress: a possible pathogenesis of atrial fibrillation.
AB  - Atrial fibrillation (AF) is the most commonly sustained arrhythmia in clinical
      practice. Despite the extensive studies, the pathophysiology of AF, however,
      remains incompletely understood. Studies have demonstrated that oxidative stress
      may be involved in cardiac structural and electrical remodeling. More recently, a
      growing body of evidence suggests that oxidative stress is associated with the
      development of AF. The evidence for the hypotheses included that: (1)
      histological studies have demonstrated oxidative damage in both AF patients and
      animal models of AF; (2) oxidative stress markers are increased in AF patients,
      and are associated with the presence of AF; (3) drugs that have antioxidant
      properties show beneficial effects on AF development. Although the studies
      suggest the association between oxidative stress and AF, the exact pathogenesis
      of oxidative stress in AF development remains elusive and requires further
      investigation. Specifically, the causality between oxidative stress and AF; the
      levels of the oxidative stress in various types of AFs and their role in the
      pathogenesis of AF; the effects of strategies to reduce oxidative stress on
      atrial structural and electrical remodeling, and their exact role in the
      development of AF. Oxidative stress may provide a scientific basis for further
      research on the underlying mechanisms of AF and may target for pharmacological
      interruption of AF.

PMID- 19103472
TI  - Detection of circulating tumor cells in bladder cancer patients.
AB  - The methods employed for the detection of circulating bladder cancer cells (CBCs)
      and their use as a molecular staging tool in clinical settings are thoroughly
      reviewed. CBC isolation and enrichment methods are discussed according to their
      advantages and pitfalls along with the clinical data of PCR-based techniques used
      for CBC detection. In addition, we review the specificity of molecular markers
      that have been proposed so far for CBC identification, and we comment on the
      controversial clinical data, proposing laboratory approaches which may improve
      the clinical significance of CBC detection in bladder cancer.

PMID- 19103474
TI  - Self organized mapping of data clusters to neuron groups.
AB  - T. Kohonen's self organizing map (SOM) may be considered as a plausible structure
      for modelling pattern recognition processes in the brain. Neighborhood
      preservation corresponds closely to what is called somatotopy in the
      neurosciences, and the context specificity of mappings observed (e. g. in
      malfunctions of the brain) becomes easily explicable in the framework of the SOM.
      However, there are two features which impair the aptitude of the classical SOM
      for neurophysiological models: the adaptation procedure is explicitly time
      dependent and the procedure consumes the whole set of disposable neurons. Because
      of the latter property, a SOM cannot learn different tasks, adapting one subset
      of neurons to a data set Chi(1) and another to a subsequently presented data set
      Chi(2). The present paper describes a modified SOM which avoids the drawbacks
      mentioned above. Its adaptation procedure is time independent. When the training
      sequence consists of data from successive data clusters Chi(k) each cluster is
      mapped to a subset G(k) of the neuron set G while the other neurons are left
      almost unchanged. The behavior of the resulting DCNG-SOM is demonstrated in
      several experiments.

PMID- 19103475
TI  - Modular network SOM.
AB  - This study aims to develop a generalized framework of an SOM called a modular
      network SOM (mnSOM). The mnSOM has an array structure consisting of functional
      modules that are trainable neural networks, e.g., multi-layer perceptrons (MLPs),
      instead of the vector units of the conventional SOM. In the case of MLP-modules,
      an mnSOM learns a group of systems or functions in terms of the input-output
      relationships in parallel with generating a feature map of them. Thus an mnSOM
      with MLP modules is an SOM in function space rather than in vector space. In this
      paper, first, as an example, we focus on a class of mnSOM that consists of MLP
      modules and introduce the architecture and algorithm. Then, a more generalized
      framework is described. Finally, some simulation results of an MLP-module-mnSOM
      are presented.

PMID- 19103476
TI  - Reduced fractional anisotropy of corpus callosum in first-contact, antipsychotic
      drug-naive patients with schizophrenia.
AB  - BACKGROUND: Corpus callosum is the most important commissure of the brain and
      therefore represents a first-choice candidate to challenge hypotheses of
      disrupted inter-hemispheric connectivity and white matter pathology in patients
      with schizophrenia. Recent studies on diffusion tensor imaging (DTI) of corpus
      callosum yielded promising but equivocal evidence of reduced fractional
      anisotropy (FA) in schizophrenia patients who were, for the most part, chronic
      cases on medication for a lengthy period of time. To exclude potentially
      confounding effects of the course of the disorder and its treatment, we compared
      callosal FA of first-contact, antipsychotic drug-naive schizophrenia patients
      (n=21) and healthy controls (n=21). METHODS: Splenium and genu FA were obtained
      by two independent observers utilizing large, rectangular, tractography-guided
      regions of interest outlined on directional color-coded maps. Inter-observer
      agreement on FA was evaluated by means of the Bland and Altman and the Passing
      and Bablok procedures together with an estimate of the intra-class correlation
      coefficient. RESULTS: Strong inter-observer agreement of FA values emerged from
      each of the three statistical approaches utilized. ANCOVA showed a significant
      effect on FA for the interaction between patient-control membership and callosal
      region (F=5.354; p=0.026); post hoc multiple comparisons demonstrated that, when
      compared to the controls, the patients had lower mean FA values (p=0.005) in the
      splenium but not in the genu and that this difference tended to be more evident
      in males (p=0.090). CONCLUSIONS: Lowered mean FA values in the splenium of first
      contact, antipsychotic drug-naive patients with respect to healthy controls
      strongly support the hypothesis that processes operant at least since the
      earliest phases of the disorder and independent from exposition to antipsychotic
      drugs contribute to reduced anisotropy in schizophrenia.

PMID- 19103477
TI  - Antinociceptive activity of 1-nitro-2-phenylethane, the main component of Aniba
      canelilla essential oil.
AB  - Aniba canelilla (H.B.K.) Mez is a medicinal plant used in the Amazon folk
      therapeutic as antispasmodic, antidiarreic, carminative, tonic agent and a
      stimulant of the digestive and central nervous system. Our preliminary studies
      showed that the plant essential oil has analgesic activity in mice. Now, we are
      reporting the antinociceptive effect of the compound 1-nitro-2-phenylethane
      (97.5%), the main component of the essential oil of Aniba canelilla, which was
      obtained by column chromatographic purification. In the writhing test this
      compound was dosed at 15, 25 and 50 mg/kg reducing the abdominal writhes in a
      significant manner; in the hot plate test it was assayed at 50, 100 and 200 mg/kg
      producing no alterations in the latency time when compared to the control; and in
      the formalin test the 1-nitro-2-phenylethane was tested at 50 and 25 mg/kg
      decreasing significantly the second phase of the algic stimulus. The study
      suggests that the 1-nitro-2-phenylethane has analgesic activity, probably of
      peripheral origin. The mechanism involved is not completely understood, however,
      the results suggest that the opioid receptors are involved in the antinociceptive
      action observed to 1-nitro-phenylethane.

PMID- 19103478
TI  - Herbal melanin activates TLR4/NF-kappaB signaling pathway.
AB  - Expression of many pro-inflammatory cytokines is controlled by the NF-kappaB
      signaling pathway. NF-kappaB is induced by LPS through activation of TLR4.
      Melanins extracted from fungal, plant and human sources modulate cytokine
      production and activate NF-kappaB pathway. We showed that a herbal melanin (HM)
      from Nigella sativa L. modulates cytokine production and suggested it as a ligand
      for TLR4. In this study we investigated the possibility that the HM-induced
      cytokine production is via an NF-kappaB signaling pathway. We found that HM
      induced the degradation of IkappaBalpha, a key step in the activation of NF
      kappaB. Moreover, addition of IkappaB kinase (IKK) specific inhibitors
      effectively inhibited the observed HM-induced production of IL-8 and IL-6 by TLR4
      transfected HEK293 cells and THP-1 cells. Our results have also shown that HM
      induced cleavage of caspase 8, and that this cleavage was partially abrogated by
      IKK inhibitors. We suggest that HM can modulate the inflammatory response by
      inducing IL-8 and IL-6 production via TLR4-dependent activation of the NF-kappaB
      signaling pathway.

PMID- 19103480
TI  - Sensorized waste collection container for content estimation and collection
      optimization.
AB  - The concurrent effects of a fast national growth rate, of a large and dense
      residential area and a pressing demand for urban environmental protection create
      a challenging framework for waste management in Pudong New Area, Shanghai. The
      complexity of context and procedures is indeed a primary concern of local
      municipal authorities due to problems related to the collection, transportation
      and processing of residential solid waste. In order to design and implement a
      suitable urban solid waste system, the first task is to forecast the quantity and
      variance of solid waste as it relates to residential population, consumer index,
      season, etc. The system here discussed addresses exactly these issues, by means
      of an intelligent, sensorized container. The container has been prepared and
      tested in the Pudong New Area, Shanghai.

PMID- 19103479
TI  - Primary care of the patient with chronic obstructive pulmonary disease in Italy.
AB  - Using a general practice research database with general practitioner (GP)
      clinical records, it has been observed that among the 617,280 subjects registered
      with 400 Italian GPs, 15,229 (2.47%) patients were suffering from chronic
      obstructive pulmonary disease (COPD). Of these, 67.7% had a chest radiograph at
      least once in a period of 10 years (1997-2006), while in the same period only
      31.9% had a spirometry, 29.9% had a visit to a specialist, and 0.94% had a visit
      to an allergologist. From 1997 to 2006, 7.5% of patients with COPD, especially
      the oldest ones, were hospitalized at least once for the disease, although 44.0%
      of all patients with COPD were hospitalized for other pathologies. With regard to
      treatment, in 2006, 10,936 (71.1%) of COPD patients received at least one drug
      for their disease (drugs classified within the R03 therapeutic pharmacological
      subgroup of the Anatomical Therapeutic Chemical Classification). In particular,
      salmeterol/fluticasone was prescribed 6441 times, tiotropium 4962, theophylline
      3142, beclomethasone 2853, salbutamol 2256, formoterol 2191,
      salbutamol/beclomethasone 2129, oxitropium 1802 and formoterol/budesonide 1741
      times. Based on these findings, the level of COPD management in Italy seems to
      fall short of recommended international COPD guidelines. In particular, it
      appears that GPs usually prescribe treatment without the use of spirometry,
      and/or without taking into account the severity of airway obstruction. It must
      also be noted that, in general, patients with COPD are undertreated.

PMID- 19103481
TI  - Enhanced production of medium-chain-length polyhydroxyalkanoates (PHA) by PHA
      depolymerase knockout mutant of Pseudomonas putida KT2442.
AB  - Pseudomonas putida KT2442 is a medium-chain-length polyhydroxyalkanoates (PHA)
      producer. One of the main shortages in the production of PHA has been the
      intracellular PHA degradation caused by its endogenous PHA depolymerase. The aim
      of this study was to improve PHA production via removing the PHA degradation
      mechanism. PHA depolymerase phaZ knockout mutant P. putida KTMQ01 was
      successfully constructed, which accumulated 86 wt% medium-chain-length PHA (mcl
      PHA) when cultured in mineral medium containing sodium octanoate as the carbon
      source compared with P. putida KT2442 which produced only 66 wt% of its cell dry
      weight (CDW). P. putida KTMQ01 cultured over a five-day period on sodium
      octanoate produced 4.5 g L(-1)-4.0 g L(-1) CDW containing approximately 80 wt%
      PHA without degradation. In contrast, P. putida KT2442 was observed with
      decreasing CDW and PHA from over 4 to less than 2 g L(-1) over the same period of
      time, indicating the function of PHA depolymerases which reduced the amount of
      PHA from around 50 wt% to none over the incubation period. RT-PCR analysis showed
      that phaC2 transcriptional level of P. putida KTMQ01 was higher than that of P.
      putida KT2442, indicating the possibility of relief on negative control of phaC2
      transcription by the deletion of phaZ, which combined with the lack of in vivo
      PHA degradation, led to more PHA accumulation. P. putida KTMQ01 contained PHA
      granules with larger sizes and smaller numbers than those of P. putida KT2442.

PMID- 19103482
TI  - Shortcut nitrification-denitrification by real-time control strategies.
AB  - The study aimed at solving the instability of shortcut nitrification
      denitrification through real-time control strategies. The results showed that
      excess aeration (aeration was still on after nitrosation) had an adverse impact
      on the stabilization of shortcut nitrification-denitrification, with nitrosation
      ratio (NO(2)(-)-N/NO(x)(-)-N) decreasing from 96% to 29% after excess aeration
      for 13 cycles, indicating that excess aeration was prone to change nitrification
      modes from shortcut nitrification to full nitrification. By using real-time
      control, shortcut nitrification and full nitrification were clearly detected by
      characteristic points on ORP and pH curves. Thus, aeration was stopped once
      nitrosation was completed, and shortcut nitrification-denitrification was
      maintained with nitrosation ratio (NO(2)(-)-N/NO(x)(-)-N) higher than 96%. The
      study showed that real-time control strategy could prevent excess aeration and
      achieve stable shortcut nitrification-denitrification.

PMID- 19103483
TI  - Synthesis and evaluation of photoreactive probes to elucidate iodide efflux in
      thyrocytes.
AB  - Four photoreactive analogues of 3-biphenyl-4'-yl-5,6-dihydroimidazo[2,1
      b]thiazole were prepared and evaluated as iodide sequestering agents in sodium
      iodide symporter-expressing cells. One of these new photoactivatable compounds
      retained biological activity and was further radiolabeled with tritium. This
      compound may provide a useful tool for labeling, purification, and identification
      of target protein responsible for iodide efflux in thyrocytes.

PMID- 19103484
TI  - Matched molecular pair analysis of activity and properties of glycogen
      phosphorylase inhibitors.
AB  - Matched molecular pair analysis has been used in design of inhibitors of glycogen
      phosphorylase.

PMID- 19103485
TI  - Preliminary biological evaluations of new thalidomide analogues for multiple
      sclerosis application.
AB  - The present work deals with the synthesis of a new series of thalidomide
      derivatives for therapeutic applications. These compounds were evaluated in vitro
      on a human endothelial cell line EA.hy926 for their antiproliferative potential
      and in vivo on an experimental animal multiple sclerosis model called EAE as
      angiogenesis inhibitors. The preliminary results obtained on EAE assays seem to
      validate that anti-angiogenesis compounds could be promising tools for the
      treatment of MS.

PMID- 19103486
TI  - Synthesis of novel Gn-RH analogues using Ugi-4MCR.
AB  - An efficient method for the synthesis of some Gn-RH analogues based on Ugi
      reaction has been developed. Four-component reaction of N- and C-terminus
      peptides, aromatic aldehydes and isocyanides affords novel Gn-RH analogues
      derived from triptorelin and gonadorelin. All of the products were purified using
      preparative HPLC and the structures were assigned according to MALDI-mass
      spectrometry data.

PMID- 19103487
TI  - Insight into the effects of chiral isomers quinidine and quinine on CYP2D6
      inhibition.
AB  - The distinct inhibitory effects against CYP2D6 enzyme of the stereoisomers
      quinidine and quinine were investigated in this work by employing various
      methods, including the comparative molecular field analysis (CoMFA), the
      comparative molecular similarity indices analysis (CoMSIA), the molecular
      electrostatic potential (MEP) analysis and the docking method. Several 3D-QSAR
      models with proper reliability were well established, with a CoMFA model with
      steric and electrostatic fields exhibiting 0.67, 0.99 and 0.88 of q(2), r(2) and
      r(pred)(2), respectively, a CoMSIA model with steric, electrostatic and H-bond
      acceptor fields displaying 0.72, 0.97 and 0.84 of q(2), r(2) and r(pred)(2),
      respectively. These models and related docking results reveal that quinidine
      binds to CYP2D6 in an inverse orientation as compared with quinine. Moreover,
      quinidine blocks the entrance of the active pocket of CYP2D6 more closely than
      quinine does, which explains well why the inhibitory activity of quinidine is of
      2 magnitudes larger than quinine. This investigation provides a better
      understanding of the stereoisometric effects on the bioactivities of the chiral
      isomers quinidine and quinine interacting with CYP2D6.

PMID- 19103488
TI  - Synthesis of riccardin C and its seven analogues. Part 1: The role of their
      phenolic hydroxy groups as LXRalpha agonists.
AB  - Riccardin C, a nuclear receptor LXRalpha selective agonist, is an 18-membered
      macrocyclic bisbibenzyl isolated from several liverworts. Synthesis of riccardin
      C and its seven O-methylated derivatives was accomplished. The synthetic sequence
      highlights an intramolecular Suzuki-Miyaura coupling in the formation of the 18
      membered biaryl linkage present in riccardin C. The structure-activity
      relationship of these compounds suggests that all of the phenolic hydroxy groups
      present in riccardin C are essential for the activation of LXRalpha.

PMID- 19103489
TI  - Pharyngo-laryngeal discomfort after breast surgery: comparison between
      orotracheal intubation and laryngeal mask.

PMID- 19103490
TI  - A survey of wound care provision within one English health care district.
AB  - Wound healing remains a largely overlooked area despite the perceived large
      numbers of people with wounds and the high costs of treatment. The lack of
      visibility for wounds and wound healing may in part stem from the fragmented
      nature of the available data on wound occurrence often limited to descriptions of
      specific wound types within single care settings. A survey was undertaken across
      all care providers serving the population of Bradford, UK to identify the number
      of people with wounds, the characteristics of their wounds and the allocated
      interventions used to prevent and heal wounds. In March 2007, 1735 completed
      questionnaires were returned each marking the most severe wound experienced by a
      patient. The overall prevalence of wounds was 3.55 people with wounds per 1000
      population (prevalence 0.355% 95% CI 0.33-0.37%). Almost one third (n = 556) of
      the people with wounds were located in acute care settings with the remainder
      spread across several community locations including residential and nursing
      homes. The most prevalent forms of wound were acute wounds (n = 826) followed by
      leg ulcers (n = 482) and pressure ulcers (n = 363). A previous survey with
      broadly similar methodology had shown a lower prevalence of wounds (0.279% 95% CI
      0.26-0.29%) with this difference perhaps explained by different data collection
      methodologies within the nursing home sector that resulted in a 100% return
      compared with 50% in the earlier survey.

PMID- 19103491
TI  - Bryan cervical disc prostheses: preservation of function over time.
AB  - Preserving the function of cervical disc prostheses, even over the short term, is
      a matter of concern among surgeons. Our case series highlights our results and
      protocol for increasing the probability of continued device function. Twenty-five
      consecutive patients with a mean (+/-SEM) age of 44.3+/-8.3 years underwent 29
      cervical total disc arthroplasties for disc herniations. Three patients underwent
      primary bilevel arthroplasty, and one patient underwent a second arthroplasty for
      another herniation 2 years after the first. Prosthesis ranges of motion were
      measured using dynamic plain X-ray studies and compared to the ranges of motion
      of adjacent segments. At follow-up, all prostheses were in the correct location
      and without subsidence. All displayed firm secondary stability. One segment had
      fused. Twenty-eight of 29 devices were mobile an average of 9.5 degrees +/-4.7
      degrees (range 3 degrees to 20 degrees ) (for all 29 devices the average movement
      angle was 9.2 degrees +/-5 degrees ; range 0 degrees to 20 degrees ), 25 upper
      adjacent segments were mobile an average of 10.9 degrees +/-4.5 degrees (range 2
      degrees to 20 degrees ) (excluding the fused prosthesis: 11 degrees +/-4.6
      degrees ) and 15 lower adjacent segments were mobile an average of 9.8 degrees +/
      6 degrees (range 1 degrees to 21 degrees ). With our protocol, 28 of 29 cervical
      disc prostheses in 25 consecutive patients were mobile after an average of 22.3+/
      9.4 months. Prosthesis motion was physiological and very similar to that of the
      healthy adjacent segments. Long-term studies including larger numbers of patients
      are required to validate our initial observations.

PMID- 19103492
TI  - Intraoperative electrophysiological monitoring in microvascular decompression for
      hemifacial spasm.
AB  - We aimed to determine the reliability of (i) intraoperative monitoring by
      stimulated electromyography (EMG) of the facial nerve to predict the completeness
      of microvascular decompression (MVD) for hemifacial spasm (HFS), and (ii)
      brainstem auditory-evoked potential (BAEP) to predict postoperative hearing
      disturbance. We conducted a prospective study of 36 patients who received MVD for
      HFS. We confirmed the disappearance of an abnormal muscle response in the facial
      nerve EMG to predict the completeness of MVD, and performed BAEP monitoring to
      predict postoperative hearing disturbance. The sensitivity, specificity and
      accuracy of facial nerve EMG and BAEP monitoring were evaluated. The sensitivity,
      specificity and accuracy of facial nerve EMG were 0.97, 1.0 and 0.97,
      respectively, and that for BAEP monitoring were 1.0, 0.94 and 0.94 respectively.
      There was one false positive result for facial nerve EMG, and two false positive
      results for BAEP monitoring. No false negative result was encountered for either
      EMG or BAEP monitoring. Facial nerve EMG correctly predicted whether MVD was
      successful in 35 out of 36 patients, and BAEP correctly predicted whether there
      was postoperative hearing disturbance in 34 out of 36 patients. Intraoperative
      facial nerve EMG provides a real-time indicator of successful MVD during an
      operation while BAEP monitoring may provide an early warning of hearing
      disturbance after MVD.

PMID- 19103493
TI  - Sinonasal inverted papilloma mimicking a pituitary macroadenoma.
AB  - We report the rare entity of an inverted papilloma arising from the sphenoid
      sinus that we expected to be a pituitary tumour on the basis of history,
      examination and pre-operative investigations, especially MRI appearance. Inverted
      sinonasal papilloma should be considered in the differential diagnosis of
      pituitary macroadenoma invading the sphenoid sinus.

PMID- 19103494
TI  - Prevention of brisk hyperactive response during selective dorsal rhizotomy in
      children with spasticity: isoflurane versus sevoflurane maintenance anesthesia.
AB  - In children with spasticity, deep tendon reflexes are hyperactive and even
      stimulation of normal dorsal rootlets can produce exaggerated full-strength,
      single-twitch responses in the muscles they innervate. This phenomenon is called
      the brisk hyperactive response (BHR). The aim of this study was to compare the
      efficacy of 2 volatile anesthetics, isoflurane and sevoflurane, for suppressing
      the confounding effect of BHR during selective dorsal rhizotomy (SDR) in children
      with spasticity. The subjects were 54 consecutive children of American Society of
      Anesthesiology physical status III who were scheduled for SDR. After tracheal
      intubation, each child was randomly assigned to Group I (isoflurane; n=27) or
      Group S (sevoflurane; n=27). There was no significant difference between the mean
      operation times in Groups I and S (200+/-40 vs. 220+/-35 minutes, respectively;
      p=0.0559). Thirteen patients in Group I (48.1%) and 5 in Group S (18.5%)
      exhibited BHR during stimulation of the dorsal rootlets (odds ratio 4.086;
      p=0.0418). Three of these 18 patients (2 in Group I and 1 in Group S) experienced
      hypertension and tachycardia simultaneously with BHR (odds ratio 4.086; p=1.0).
      The results suggest that sevoflurane is more effective at preventing BHR and
      might be a better choice for anesthetic management of children with spasticity
      undergoing SDR.

PMID- 19103495
TI  - Thiazole Orange derivatives: synthesis, fluorescence properties, and labeling
      cancer cells.
AB  - A series of Thiazole Orange (TO) derivatives were synthesized and modified by
      introducing different substitutional groups on benzothiazole and 4
      methylquinoline All the TO derivatives were confirmed by (1)HNMR and MS. TO
      derivative bearing NH(2)- was modified by folic acid and used to label breast
      cancer cells. The phenomenon of fluorescence enhancement was shown by the
      fluorescence spectrums of TO derivatives and micrographs of the labeled breast
      cancer cells. It offered a new try in the aspect of labeling cells by the
      embedded dyes.

PMID- 19103496
TI  - Fragmentation of isomeric intrastrand crosslink lesions of DNA in an ion-trap
      mass spectrometer.
AB  - The collision-induced dissociation pathways of isomeric cytosine-guanine and
      cytosine-adenine intrastrand crosslink-containing dinucleoside monophosphates
      were investigated with the stable isotope-labeled compounds to gain insights into
      the effects of chemical structure on the fragmentation pathways of these DNA
      modifications. A Dimroth-like rearrangement, which was reported for protonated 2'
      deoxycytidine and involved the switching of the exocyclic N4 with the ring N3
      nitrogen atom, was also observed for the cytosine component in the protonated
      ions of C[5-8]G, C[5-2]A, and C[5-8]A, but not C[5-N(2)]G or C[5-N(6)]A. In these
      two sets of crosslinks, the C5 of cytosine is covalently bonded with its
      neighboring purine base via a carbon atom on the aromatic ring and an exocyclic
      nitrogen atom, respectively. On the contrary, the rearrangement could occur for
      the deprotonated ions of C[5-N(2)]G, C[5-N(6)]A, and unmodified cytosine, but not
      C[5-8]G, C[5-2]A, or C[5-8]A. In addition, ammonia could be lost more readily
      from C[5-N(2)]G and C[5-N(6)]A than from C[5-8]G, C[5-2]A, and C[5-8]A. The
      results from the present study afforded important guidance for the application of
      mass spectrometry for the structure elucidation of other intrastrand/interstrand
      crosslink lesions.

PMID- 19103497
TI  - Correct charge state assignment of native electrospray spectra of protein
      complexes.
AB  - Correct charge state assignment is crucial to assigning an accurate mass to
      supramolecular complexes analyzed by electrospray mass spectrometry. Conventional
      charge state assignment techniques fall short of reliably and unambiguously
      predicting the correct charge state for many supramolecular complexes. We provide
      an explanation of the shortcomings of the conventional techniques and have
      developed a robust charge state assignment method that is applicable to all
      spectra.

PMID- 19103498
TI  - Mass spectrometry analysis of photo-induced methionine oxidation of a recombinant
      human monoclonal antibody.
AB  - Oxidation of methionine (Met) residues of a recombinant fully human monoclonal
      antibody after exposure to light was investigated and compared with chemically
      induced oxidation using tert-butyl-hydroperoxide (tBHP). Met256 and Met432 in the
      Fc region in the samples exposed to light or incubated with tBHP were oxidized.
      The Fc mass spectra of the antibody exposed to light showed mainly peaks with a
      molecular weight (MW) increase of 32 Da, however the sample treated with tBHP
      showed peaks with increase of only 16 Da. These results suggested that either
      oxidation of one Met residue (either Met256 or Met432) catalyzed the oxidation of
      the second Met residue on the same heavy chain (HC) or Met residues of one HC
      were preferentially oxidized when the antibody was exposed to light, while Met256
      and Met432 were randomly oxidized when the antibody was incubated with tBHP.

PMID- 19103499
TI  - N-terminal B-natriuretic Peptide after coronary artery bypass graft surgery.
AB  - OBJECTIVE: To investigate N-terminal amino-acid sequence of the B-natriuretic
      peptide (NT-proBNP) release and its prognostic characteristics after coronary
      artery bypass graft surgery with and without cardiopulmonary bypass. DESIGN:
      Observational study. SETTING: Teaching hospital. PARTICIPANTS: One hundred eighty
      four patients. INTERVENTIONS: The authors determined plasma concentrations of NT
      proBNP just before anesthesia induction and 24 hours after the end of the
      surgery. MEASUREMENTS AND MAIN RESULTS: NT-proBNP concentrations (median
      [interquartile range]) increased from 270 (75-716) pg/mL preoperatively to 1,664
      (978-3,193) pg/mL on postoperative day 1 (p < 0.001), and all postoperative
      values were higher than the preoperative ones. NT-proBNP concentrations at day 1
      were correlated to those at day 0 (r(2) = 0.34, p < 0.001). Patients showing
      elevated concentration of cTnI at day 1 (>14 ng/mL) had significantly (p = 0.04)
      higher plasma NT-proBNP levels than patients with a low cardiac troponin I
      concentration. Patients with prolonged intensive care unit (ICU) stay (>4 days)
      showed at day 1 significantly higher (p = 0.003) plasma NT-proBNP levels than
      patients with ICU stay <4 days. Elevated NT-proBNP at day 1 was significantly (p
      = 0.001) associated with in-hospital mortality, 18,584 (11,896-29,158) pg/mL
      versus 1,597 (965-3,034) pg/mL in survivors. CONCLUSIONS: The present results
      show, for the first time, that postoperative NT-proBNP levels are associated with
      in-hospital mortality and prolonged ICU stay after CABG surgery. These findings
      support the prognostic value of postoperative plasma levels of NT-proBNP.

PMID- 19103500
TI  - Tranexamic acid reduces blood loss in off-pump coronary artery bypass surgery.
AB  - OBJECTIVE: This study was designed to evaluate the hemostatic effect of
      tranexamic acid in off-pump coronary artery bypass surgery. DESIGN: A
      prospective, randomized, double-blind, placebo-controlled study. SETTING: The
      Department of Anesthesiology and Cardiac Surgery, Medical Sciences University.
      PARTICIPANTS: One hundred eight patients undergoing off-pump coronary artery
      bypass surgery were enrolled into the study. Eight patients were withdrawn, and
      100 patients were divided into 2 groups. INTERVENTIONS: Fifty patients received
      tranexamic acid (bolus 1 g before skin incision and followed by maintenance dose
      of 400 mg/h during surgery), and 50 patients received saline. MEASUREMENT AND
      MAIN RESULTS: Hematologic parameters, volume of blood loss, blood transfusion,
      and other clinical data were recorded throughout the perioperative period. Twenty
      four-hour postoperative blood loss was significantly less in the tranexamic acid
      group compared with the control group (471 +/- 182 v 844 +/- 303). Patients in
      the tranexamic acid group received significantly less allogeneic blood (8 v 31
      units). CONCLUSION: Bleeding and hemorrhagic complications and the consequent
      need for allogeneic transfusion are still major problems after off-pump coronary
      artery bypass surgery. Tranexamic acid appears to be effective in reducing
      postoperative bleeding and the need for allogeneic blood products.

PMID- 19103501
TI  - Minimally invasive, minimally reimbursed? Anesthesia for endoscopic cardiac
      surgery is not reflected adequately in the german diagnosis-related group system.
AB  - OBJECTIVES: In the German diagnosis-related group (G-DRG) system, hospital
      reimbursement for anesthesia is linked to specific surgical procedures,
      irrespective of case duration. Accordingly, costs of innovative procedures, such
      as endoscopic cardiac surgery, may be underreimbursed. The authors assessed to
      what extent anesthesia costs for endoscopic cardiac surgery are reimbursed with
      the G-DRG system. DESIGN: Retrospective analysis. SETTING: University hospital.
      PARTICIPANTS: Eighty-four patients were studied undergoing general anesthesia for
      minimally invasive endoscopic port-access intracardiac surgery (n = 42) or
      conventional "open" surgery (n = 42) for similar indications. INTERVENTIONS:
      None. MEASUREMENTS AND MAIN RESULTS: The authors measured anesthesia staffing
      time, costs, and reimbursement for endoscopic cardiac surgery and compared
      results with data from a matched group undergoing conventional surgery.
      Endoscopic surgery increased anesthesia staffing time per case by 521 minutes
      (977 minutes +/- 177 v 456 +/- 92, mean +/- standard deviation, p = 0.0001) and
      costs by approximately 200%. Anesthesia duration increased by 152 minutes (503
      minutes +/- 89 v 351 +/- 69, p = 0.0001). In contrast, staffing reimbursement did
      not increase at the time of the patient's surgery (euro500/case [446-569] v 492
      [452-508], p = 0.75, median [interquartile range]) or with the 2007 G-DRG matrix
      (euro548/case [463-559] v 503 [503-568], p = 0.48). Cost recovery was only 66% +/
      17.4% and 72.7 +/- 38.9 in the 2007 G-DRG matrix, respectively. CONCLUSIONS: It
      was shown that (1) endoscopic cardiac surgery consumed more anesthesia resources
      and was underreimbursed both relative to actual costs and to conventional
      surgery, (2) costs for such anesthesia services were inappropriately reflected in
      the G-DRG system, and (3) a DRG system's inability to adapt timely to innovative
      procedures may adversely affect anesthesia departments and medical progress.

PMID- 19103502
TI  - Intra-articular injections of hyaluronan solutions of different elastoviscosity
      reduce nociceptive nerve activity in a model of osteoarthritic knee joint of the
      guinea pig.
AB  - OBJECTIVE: To study in guinea pigs knee joints the effects of intra-articular
      injection of HYADD 4-G (Fidia-Farmaceutici), a novel hyaluronan (HA)-derived
      elastoviscous material and of Hyalgan (Fidia-Farmaceutici), a HA product with
      very low viscoelasticity, on movement-evoked nociceptor impulse activity from
      normal and inflamed knee joints. DESIGN: Nociceptor impulse activity was recorded
      from single Adelta and C fibers of the medial articular nerve either under
      control conditions or after induction of an experimental knee joint
      osteoarthritis (OA) by partial medial menisectomy and transection of the anterior
      cruciate ligament (PMM-TACL). The stimuli consisted of standardized innocuous and
      noxious inward and outward rotations of the tibia against the femur of 50s
      duration, repeated every 5min for 1.5h. RESULTS: The number of movement-evoked
      impulses was significantly augmented 1 day and 1 week after PMM-TACL compared
      with intact knee joint. The enhanced impulse response to joint movements 1 week
      following surgery was attenuated by repeated intra-articular injection of HYADD 4
      G and even more prominently by Hyalgan. CONCLUSIONS: HA products have a reducing
      action on joint nociceptor discharges that appears to depend predominantly on
      their role as an elastoviscous filter associated with their rheological
      properties, but also on a chemical effect on sensitized nociceptive terminals of
      inflamed joint tissues, possibly linked to the HA concentration.

PMID- 19103503
TI  - Eyelid multiple cysts of the apocrine gland of Moll in Persian cats.
AB  - Feline eyelid hidrocystoma is a rarely reported disease of the apocrine glands of
      Moll that has been variably interpreted as proliferative/neoplastic lesion or
      retention cyst. The purpose of this paper was to investigate feline hidrocystoma
      pathogenesis by means of a histological and immunohistochemical study. Nine
      paraffin embedded biopsies of eyelid hidrocystoma were retrieved from our
      archives. Histological sections were immunostained with antibodies anti
      cytoskeletal proteins and Ki67 antigen. All hidrocystomas were observed in
      Persian cats, seven males/two females, mean age 9.6 years. Histologically, single
      or multiple, variably sized cysts expanded eyelid dermis. Cyst was lined by
      cuboidal epithelium, occasionally raising in papillary structures. Immunostaining
      was consistent with apocrine gland epithelium (cytokeratin 8/18; 19 and 14
      positive). Ki67 immunolabelled nuclei ranged from 5.3 to 20.83%. Although it was
      not possible to draw a definite conclusion concerning hidrocystoma
      aetiopathogenesis, the relatively high Ki67-proliferative index observed,
      suggested a proliferative nature of the lesion.

PMID- 19103504
TI  - Movement irregularities in atypical parkinsonian syndromes.
AB  - This study examined discrete motor irregularities in ballistic aiming movements
      in patients with atypical parkinsonian syndromes (APS). Nine patients with APS
      were compared to 9 patients with idiopathic Parkinson's disease (PD) and 9
      controls on ballistic arm extension movements performed on a digitizing tablet
      without visual feedback and without accuracy constraints. Patients with APS
      showed a higher number of irregularities in the acceleration and jerk time series
      compared to PD patients and controls. No difference was found between PD patients
      and controls. These discrete irregularities were not associated with general
      motor impairment, tremor, akinesia, or rigidity. These results suggest that
      atypical parkinsonism is associated with movement irregularities in ballistic
      movements, which may help differentiate APS from PD.

PMID- 19103505
TI  - Opening velocity, a novel parameter, for finger tapping test in patients with
      Parkinson's disease.
AB  - OBJECTIVES: A new system consisting of an accelerometer and touch sensor was
      developed to find objective parameters for the finger tapping (FT) test in
      patients with Parkinson's disease (PD). METHODS: We recruited sixteen patients
      with PD and thirty-two age-matched healthy volunteers (HVs). By using this new
      system, various parameters related to velocity, amplitude, rhythm and number in
      the FT test were measured in patients with PD and examined in comparison with
      those of HVs on the basis of the Unified Parkinson's Disease Rating Scale (UPDRS)
      FT score. RESULTS: The new system allowed us to measure fourteen parameters of FT
      movement very easily, and a radar chart showed obvious differences in most of
      these parameters between HVs and patients with PD. Principal component analysis
      showed that fourteen parameters were classified into three components: (1) both
      mean and standard deviation (SD) of both amplitude and velocity, (2) number of FT
      for 60s and mean FT interval, and (3) SD of FT interval. The first (velocity- and
      amplitude-related parameters) and third (rhythm-related parameters) components
      contributed to discrimination of PD from HVs. Maximum opening velocity (MoV) was
      the best of these parameters because of its sensitivity and association with the
      UPDRS FT score. CONCLUSIONS: A novel system for the FT test, which is compact,
      simple and efficient, has been developed. Velocity- and amplitude-related
      parameters were indicated to be valuable for evaluation of the FT test in
      patients with PD. In particular, we first propose that MoV is a novel marker for
      the FT test.

PMID- 19103506
TI  - Action tremor of the legs in essential tremor: prevalence, clinical correlates,
      and comparison with age-matched controls.
AB  - The hallmark feature of essential tremor (ET) is action tremor of the arms. Leg
      tremor may also occur yet it has not been the central focus of previous studies.
      Its prevalence has only rarely been reported, its clinical correlates have yet to
      be explored. Our aims were to report the prevalence and analyze the clinical
      correlates of leg action tremor in patients with ET and, given the propensity for
      normal elderly individuals to manifest mild limb tremors, compare the prevalence
      with that in age-matched controls. Kinetic leg tremor rated > or =1 occurred in
      28/63 (44.4%) ET cases and in only 9/63 (14.3%) controls (p<0.001); moderate leg
      tremor occurred in 14.3% of cases. Leg tremor severity modestly correlated with
      disease duration (r=0.31, p=0.02). However, the severity and laterality of leg
      tremor did not correlate with those of arm tremor. The pathophysiological
      implications of this finding deserve further exploration.

PMID- 19103507
TI  - Transmandibular approach for excision of maxillary sinus tumors extending to
      pterygopalatine and infratemporal fossae.
AB  - En bloc resection of maxillary sinus tumors that extend through the posterior
      wall necessitates resection of maxilla along with pterygopalatine and
      infratemporal fossae contents. This cannot be readily performed by conventional
      anterior maxillectomy approaches. The objective of this study is to evaluate the
      effectiveness of transmandibular approach for the excision of maxillary sinus
      tumors extending to pterygopalatine and infratemporal fossae. This is a
      retrospective review of 15 consecutive patients who underwent maxillectomy with
      transmandibular approach for tumors with posterior extension, between January
      2004 and February 2008. The principal outcome parameter was the margin status on
      final histopathology report. In addition, evaluable patients were reviewed to
      assess the morbidity of the procedure using pre-defined parameters. All the
      patients had negative margins at the infratemporal fossa region. Varying degree
      of trismus was present in all patients. The cosmetic outcome of the procedure was
      excellent. Other anterior and transcranial approaches could be combined with this
      procedure when indicated. We conclude that transmandibular approach is an
      effective technique for resection of maxillary tumors with posterior extension to
      the pterygopalatine and infratemporal fossae. The procedure has acceptable
      morbidity and the aesthetic and functional results are satisfactory.

PMID- 19103508
TI  - Evaluation of immobility time for sleep latency in actigraphy.
AB  - BACKGROUND: Actigraphy has become an important tool in sleep research, however,
      most actigraphic models have had little evaluation of their sleep scoring
      software. Some reports have described poor agreement of actigraph and
      polysomnogram (PSG) results. In this study, we examined the accuracy of the
      Actiwatch-L instrument with Actiware((R)) software version 5.0 (Minimitter
      Respironics, Bend, Oregon). METHODS: We analyzed the sleep latencies and total
      sleep times in 33 actigraph recordings and compared performance to simultaneous
      polysomnography. For scoring sleep latency, the default criterion for scoring
      sleep onset (10min of immobility) was compared with criteria of 4, 5, 6, and
      15min of immobility, and low, middle, and high activity thresholds were compared.
      RESULTS: Of 4, 5, 6, 10 and 15min of actigraphic immobility, the 5min criterion
      yielded the most accurate sleep latencies. The 5min criterion also yielded near
      optimal estimates for total sleep time and wake after sleep onset. CONCLUSIONS:
      We found that a default 10-min immobility parameter for sleep onset was not as
      accurate as 5min for scoring sleep latency and total sleep time in this clinical
      sample. There is a need for expanded samples to further evaluate algorithm
      scoring parameters and the search for superior alternatives.

PMID- 19103509
TI  - Continuous improvement of our autologous blood donation program carried out
      during 10 years in 1198 orthopaedic patients.
AB  - BACKGROUND: We analysed the relationship between baseline haemoglobin levels and
      the need for post-operative blood transfusion in our patients. The aim of this
      study was to evaluate and optimize the pre-operative autologous blood donation
      (PABD) program at our hospital through a constant audit. MATERIALS AND METHODS:
      Between January 1997 and December 2006 we evaluated 1198 consecutive patients who
      underwent elective, unilateral, primary total hip or knee arthroplasty and who
      met our inclusion criteria. We determined the baseline haemoglobin level to
      establish the relationship to the need for post-operative transfusion. RESULTS:
      The results of our study show that the baseline haemoglobin level is a strong
      predictor of blood transfusion after unilateral, primary total hip or knee
      arthroplasty. CONCLUSIONS: The baseline haemoglobin level is a strong predictor
      of blood transfusion after elective, unilateral, primary total hip or knee
      arthroplasty. On the basis of these findings, we do not recommend autologous
      predonation for patients with a baseline haemoglobin level of >14g/dl moreover we
      always recommend the use of a blood cell salvage system and a constant audit of
      pre-operative autologous blood donation (PABD) to avoid unnecessary expense and
      waste.

PMID- 19103510
TI  - Comparison of a cytokine adsorbing column and an endotoxin absorbing column for
      the treatment of experimental endotoxemia.
AB  - The present study compared the effects of direct hemoperfusion (DHP) using a
      cytokine absorbing (CTR) column with those using an endotoxin absorbing (PMX)
      column with endotoxin-induced shock in rats. Thirty-six rats were injected
      intravenously with endotoxin (15 mg/kg), and then allocated into one of the
      following three groups: control group, treated without CTR; PMX group, treated
      with a PMX column for 120 min; CTR group, treated with a CTR column for 120 min.
      The present study showed that CTR treatment decreased the mortality rate 8h after
      endotoxin injection and inhibited inflammatory responses (cytokine, hemodynamics
      and acidosis) similar to PMX treatment.

PMID- 19103511
TI  - Comparison of efficacy between continuous hemodiafiltration with a PMMA membrane
      hemofilter and a PAN membrane hemofilter in the treatment of a patient with
      septic acute renal failure.
AB  - The aim of this study was to investigate whether PMMA-CHDF in the treatment of a
      patient with septic acute renal failure (septic ARF) is clinically relevant.
      Thirteen patients were treated with PMMA-CHDF. Thirteen patients were treated
      with PAN-CHDF. The urinary output significantly increased in PMMA-CHDF group
      following 24h of the treatment (p<0.05), whereas those did not improve in PAN
      CHDF group. The 28-day survival was 84.6% in PMMA-CHDF group and 38.5% in PAN
      CHDF group, respectively (p<0.05). We can assume that the cytokine modulation
      with PMMA-CHDF in the treatment of patients with septic ARF is clinically
      relevant.

PMID- 19103512
TI  - Performance of the St. Jude Medical Riata leads.
AB  - BACKGROUND: Recent attention has been focused on the performance of high-voltage
      implantable cardioverter-defibrillator (ICD) leads. Lead-related adverse events
      can be caused by several factors, including patient characteristics, concomitant
      therapies, implantation technique, access site, and lead design. Few studies have
      included the number of patients and the follow-up duration necessary to
      characterize accurately the lead performance and the incidence of lead-related
      adverse events. OBJECTIVE: This study sought to define the incidence of lead
      related adverse events including conductor fracture, insulation damage,
      perforation, and dislodgement of St. Jude Medical Riata ICD leads. METHODS: Data
      from the Advancements in ICD Therapy, OPTIM Lead InsUlation Material (OPTIMUM),
      Resynchronization HemodYnamic Treatment for Heart Failure Management (RHYTHM),
      and Post Approval Study (PAS) registries provided data from 7,497 patients with
      Riata leads. Patients were followed up for a median of 22 months. Adverse events,
      defined as those that required lead revision, extraction, or replacement, were
      recorded. RESULTS: Conductor fracture occurred in 0.09%, insulation damage in
      0.13%, dislodgement in 0.88%, and perforation in 0.31% of patients, respectively.
      CONCLUSION: During more than 22 months of follow-up of over 7,000 Riata leads in
      4 prospective registries and clinical trials, the incidence of lead-related
      adverse events including conductor fracture, insulation damage, dislodgement, and
      perforation necessitating lead revision, extraction, or replacement is rare.

PMID- 19103513
TI  - Differential in-gel electrophoresis (DIGE) analysis of human bone marrow
      osteoprogenitor cell contact guidance.
AB  - We have used a recent comparative proteomics technique, differential in-gel
      electrophoresis (DIGE), to study osteoprogenitor cell response to contact
      guidance in grooves. In order to increase protein output from small sample sizes,
      we used bioreactor culture before protein extraction and gel electrophoresis.
      Mass spectroscopy was used for protein identification. A number of distinct
      proteins were observed to exhibit significant changes in expression. These
      changes in protein expression suggest that the cells respond to tailored grooved
      topographies, with alterations in their proteome concurrent with changes in
      osteoprogenitor phenotype.

PMID- 19103515
TI  - Should we be prescribing repeated courses of antenatal corticosteroids?
AB  - Single-course treatment with antenatal corticosteroids has been shown to enhance
      fetal maturation before preterm birth and to improve outcomes for the preterm
      infant. Based on this success, practitioners expanded use of the treatment to
      repeated courses of antenatal corticosteroids ahead of evidence demonstrating
      benefit and excluding harm. Experiments with animals and cohort studies have
      provided a body of evidence suggesting that repeated doses may further improve
      lung maturation but may be accompanied by deleterious effects on the developing
      brain and other organs. Randomised controlled trials of repeated treatments to
      date have provided mixed evidence but in general may indicate a small benefit in
      terms of postnatal lung function, but this is accompanied by restricted growth
      which may include the brain. In view of the well-established role that
      corticosteroids are known to play in brain development, and the marginal
      difference that repeated courses may make to outcome in the context of modern
      neonatal care, antenatal corticosteroid treatments should be restricted to single
      course treatment.

PMID- 19103514
TI  - Affinity-based release of glial-derived neurotrophic factor from fibrin matrices
      enhances sciatic nerve regeneration.
AB  - Glial-derived neurotrophic factor (GDNF) promotes both sensory and motor neuron
      survival. The delivery of GDNF to the peripheral nervous system has been shown to
      enhance regeneration following injury. In this study, we evaluated the effect of
      affinity-based delivery of GDNF from a fibrin matrix in a nerve guidance conduit
      on nerve regeneration in a 13 mm rat sciatic nerve defect. Seven experimental
      groups were evaluated which received GDNF or nerve growth factor (NGF) with the
      delivery system within the conduit, control groups excluding one or more
      components of the delivery system, and nerve isografts. Nerves were harvested 6
      weeks after treatment for analysis by histomorphometry and electron microscopy.
      The use of the delivery system (DS) with either GDNF or NGF resulted in a higher
      frequency of nerve regeneration vs. control groups, as evidenced by a neural
      structure spanning the 13 mm gap. The GDNF DS and NGF DS groups were also similar
      to the nerve isograft group in measures of nerve fiber density, percent neural
      tissue and myelinated area measurements, but not in terms of total fiber counts.
      In addition, both groups contained a significantly greater percentage of larger
      diameter fibers, with GDNF DS having the largest in comparison to all groups,
      suggesting more mature neural content. The delivery of GDNF via the affinity
      based delivery system can enhance peripheral nerve regeneration through a
      silicone conduit across a critical nerve gap and offers insight into potential
      future alternatives to the treatment of peripheral nerve injuries.

PMID- 19103516
TI  - Re: A simple adjunct to facilitate hand held Doppler perforator localisation
      following microsurgical breast reconstruction.

PMID- 19103517
TI  - Preoperative CT angiography for DIEP flaps: 'must-have' lessons for the
      radiologist.

PMID- 19103518
TI  - Reconstruction in the buttock region using the local fasciocutaneous infragluteal
      (FCI) flap.
AB  - BACKGROUND: Defects in the buttock region are frequent indications for plastic
      surgery and are caused by various mechanisms. Therefore, different flaps were
      introduced and are well established. However, all of them have their limitations
      in reconstruction because of their restricted arc of rotation. Hence, we
      indicated the use of the local fasciocutaneous infragluteal (FCI) flap for
      reconstruction of such defects in the buttock region. METHODS: In a series of 14
      patients, three of them being paraplegics, the authors used 15 local FCI flaps to
      cover defects in the buttock region. The defects were caused by pressure sores,
      pilonidal sinus infection with recurrence, an adenocarcinoma of the gluteal
      region, a massive abscess after intramuscular gluteal injection, lipodystrophy of
      the lateral gluteal region and by multiple operations after an infection of
      implanted hip-joint prosthesis. RESULTS: The median dimension of the flaps was
      177 cm(2). Fourteen of the 15 flaps healed uneventfully. In one patient, a re
      mobilisation of the flap was necessary after a minor, distal-flap necrosis.
      Closure of the donor site was possible in all patients without further trouble.
      One patient needed a second local FCI flap because of a new pressure sore on the
      contralateral sacral region. CONCLUSIONS: The FCI flap is not only a versatile
      and reliable free flap with different indications, but is also a good alternative
      as a local flap for defect reconstruction in the whole buttock region, as
      demonstrated in this study for the first time. It can be raised as a sensate flap
      without restrictions of mobility in ambulatory patients. The donor-site morbidity
      is minimal, and options for future flaps of the gluteal region are preserved.

PMID- 19103519
TI  - Pyogenic granuloma that responded to local injection of steroid.

PMID- 19103520
TI  - A new technique for repair of acquired split-ear-lobe deformity: the free conchal
      cartilage sandwich graft.
AB  - BACKGROUND: Split-ear-lobe repair is one of the commonest requests in cosmetic
      facial surgery. Frequently, the ear lobe split is prone to recurrence following
      surgical repair. A new technique is described that strengthens the ear lobe
      tissues using locally available conchal cartilage to prevent recurrence. A new
      classification of split ear lobe is also presented. METHODS: Twenty-two women in
      the age range from 18 to 62 years with varying grades of split ear lobe were
      operated using the technique of conchal cartilage reinforcement of ear lobe.
      Eight females had bilateral involvement, and a total of 30 split ear lobes were
      repaired. A conchal cartilage disc was harvested at the time of repair of the ear
      lobe. This disc was placed in a pocket created in the ear lobe, and the ear lobe
      was repaired over this pocket. Simultaneous re-perforation of the ear lobe was
      done in a central location through the implanted conchal disc, and stud earring
      was applied. RESULTS: Satisfactory aesthetic and functional results have been
      obtained in the series using the technique of conchal cartilage-graft
      augmentation of the ear lobe. All patients had high degree of satisfaction in
      being able to come out of the operating room with earrings on. There has been no
      stretching or re-tear of the ear lobe following implantation of conchal
      cartilage, over a follow-up period of 36 months. CONCLUSION: The conchal
      cartilage-graft sandwich procedure allows immediate re-perforation of the
      repaired ear lobe at the time of repair in a central aesthetic location, as well
      as providing necessary strength to the ear lobe; thus preventing recurrence in
      primary and recurrent, acquired split-ear-lobe deformity.

PMID- 19103521
TI  - Opposite roles of STAT and PPARgamma in the induction of p21WAF1 expression by IL
      13 in human peripheral blood monocytes.
AB  - The cyclin kinase inhibitor p21WAF1 is expressed in most, if not all,
      differentiated cells in the human body and represents an important regulator of
      cell cycle control and terminal differentiation in the monocyte/macrophage
      lineage. It has been reported in macrophage cell lines that p21WAF1 expression is
      sensitive to numerous molecules including cytokines, but nothing was known about
      p21WAF1 regulation in human peripheral blood monocytes in response to Th2
      cytokines. We report here, that IL-13 increases p21WAF1 expression in human blood
      monocytes. This induction is a transcription-dependent event, leading to an
      increase in mRNA content. We show that the signalling pathway for IL-13-induced
      p21WAF1 expression may involve the IL-4R alpha and the IL-13R alpha1 chains, and
      the tyrosine and JAK2 kinases. Also, p21WAF1 plasmid-based gene activation only
      requires a minimal p21WAF1 promoter, containing a putative PPRE. Since IL-13
      signalisation involves PPARgamma, we tested PPARgamma involvement in p21WAF1 gene
      activation by using metabolic inhibitors of arachidonic acid metabolism, or by
      restoring PPARgamma expression in a defective cell line. We found that inhibition
      of PPARgamma increases IL-13-induced p21WAF1 gene expression in these models.
      These data argue that IL-13 upregulates p21WAF1 expression in monocytes via
      JAK/STAT pathway, and that the activation of PPARgamma by this cytokine can
      counteract this induction.

PMID- 19103523
TI  - Profiling of angiogenic cytokines produced by hormone- and drug-refractory
      prostate cancer cell lines, PC-3 and DU-145 before and after treatment with
      gossypol.
AB  - In this study, we aimed to investigate the angiogenic cytokine profiles of
      hormone- and drug-refractory prostate carcinoma cell lines, PC-3 and DU-145. We
      also studied the effect of gossypol, a natural polyphenolic cotton-seed extract,
      on the angiogenic cytokine profile of these cell lines. XTT cell proliferation
      assay was used for the assessment of cytotoxicity. For apoptosis, both histone
      DNA fragmentation by ELISA assay and caspase 3/7 activity measurement were used.
      Angiogenic cytokine profiles of supernatants from both cell lines, before and
      after treatment with gossypol, were investigated using the human angiogenesis
      antibody array I. It was shown that the two different hormone- and drug-resistant
      prostate cancer cell lines, PC-3 and DU-145, constitutively express some
      important angiogenic cytokines, which are known to regulate tumorigenicity and
      angiogenesis in hormone-refractory prostate cancer. However, PC-3 and DU-145
      cells have distinct angiogenic cytokine profiles. In addition, these two cells
      lines respond differently to gossypol treatment in terms of cytotoxicity and
      angiogenic cytokine secretion. After treatment with 10 microM of gossypol, there
      was a 1.5-fold decrease in angiogenin and IL-8 levels and a 1.7- and 1.8-fold
      decrease in ENA-78 and GRO-alpha levels respectively, in DU-145 cells. For PC-3
      cells, there were 1.6- and 1.8-fold decreases in IL-8 and VEGF levels,
      respectively. We conclude that PC-3 and DU-145 cells secrete significant amounts
      of different angiogenic cytokines that may explain their aggressive nature and
      metastatic potential. Gossypol treatment affects angiogenic cytokine secretion
      from these two cell lines in a different manner. By expanding our knowledge of
      the heterogeneous biological behavior of these two cell lines, novel treatment
      approaches can be developed for the treatment of prostate cancer.

PMID- 19103522
TI  - Prokineticin 1 induces CCL4, CXCL1 and CXCL8 in human monocytes but not in
      macrophages and dendritic cells.
AB  - Prokineticin 1 and 2 (PROK1 and PROK2) are two small proteins largely expressed
      in inflammatory tissues and involved in monocyte activation and differentiation.
      The focus of this study was to evaluate whether PROK1 was able to induce
      chemokine secretion in human monocytes, in monocyte-derived macrophages and in
      monocyte-derived dendritic cells, an aspect not addressed thus far. Here, we show
      for the first time, using flow cytometry, that PROK receptors 1 and 2 are present
      on the surface of human monocytes. Subsequently, monocytes were selected to
      investigate the chemokine response after stimulation by PROK1. Our results show
      that only three chemokines (CCL4, CXCL1 and CXCL8) were significantly induced at
      both the transcript and protein level, and that PROK1 induces most potently
      CXCL8, in a dose-dependent manner. From a mechanistic point of view, by blocking
      independently Galphai protein or intracellular calcium, monocytes lose the
      ability to secrete CXCL8 in response to PROK1. Finally, we observed that CCL4,
      CXCL1 and CXCL8 secretion, following PROK1 induction, is only observed in
      monocytes and not in monocyte-derived macrophages and dendritic cells. Our
      results demonstrate that, in vitro, the differentiation status of monocytes
      influences chemokine production after stimulation by PROK1, and that this
      chemokine production is geared toward a pro-inflammatory response. This could
      represent a novel amplification loop of leukocyte recruitment, extravasation and
      tissue invasion.

PMID- 19103524
TI  - NOD2 engagement induces proinflammatory cytokine production, but not apoptosis,
      in leukocytes isolated from patients with Crohn's disease.
AB  - BACKGROUND: NOD2/CARD15 is a member of the NACHT-LRR (NLR) family of proteins,
      which recognize the muramyl dipeptide motif from bacterial peptidoglycans. NOD2
      has been shown to be involved in the pathogenesis of Crohn's disease. NLR
      proteins modulate inflammation and apoptosis, and several studies have implicated
      NOD2 in the induction of cytokines and inflammatory reactions. However, only
      scarce data are available regarding its role in apoptosis. DONORS AND METHODS:
      Neutrophils and lymphocytes isolated from the blood from four Crohn's disease
      patients homozygous for the loss-of-function 3020insC NOD2 mutation were examined
      for spontaneous and anisomycin-induced apoptosis. They were compared with cells
      from healthy controls and Crohn's disease patients bearing the wild-type NOD2
      allele. Cytokine production after stimulation of mononuclear cells (MNCs) with
      muramyl dipeptide was assessed by specific immunoassays. RESULTS: We observed
      that MNCs isolated from the blood of patients with Crohn's disease bearing the
      loss of function mutation in NOD2 displayed defective muramyl dipeptide-induced
      cytokine responses, but both granulocytes and lymphocytes from the same donors
      displayed normal apoptosis. CONCLUSIONS: NOD2 engagement by MDP mainly triggers
      cytokine activation and inflammatory reactions, but has negligible effects on
      cell apoptosis.

PMID- 19103525
TI  - IL-23R Arg381Gln polymorphism in Chilean patients with inflammatory bowel
      disease.
AB  - Crohn's disease (CD) and ulcerative colitis (UC) are multifactorial diseases with
      a genetic background. Recent results have shown that a non-synonymous, single
      nucleotide polymorphism (rs11209026, c.1142G>A, p.Arg381Gln) located in the IL
      23R gene is associated with inflammatory bowel disease (IBD). The prevalence of
      IBD is rapidly rising in Chile and there is no information about the frequency of
      this polymorphism in the Chilean population. AIM: To assess the distribution of
      DNA variants in the IL-23R gene in Chilean patients with IBD. METHODS: We studied
      100 IBD patients (38 CD and 62 UC) and 59 healthy controls. IL-23R Arg381Gln
      (G1142A) was genotyped by the polymerase chain reaction and restriction fragment
      length polymorphism assay. Clinical and demographic features were characterized.
      RESULTS: The IL-23R genetic variant did not have an association with IBD in
      Chilean patients. This polymorphism was present in 5.2% of the control group and
      5% of IBD patients (7.9% for CD and 3.2% for UC) (p > 0.05). CONCLUSIONS: These
      results suggest that the IL-23R Arg381Gln seems not to be involved in the genetic
      predisposition to IBD in a Chilean population, and confirms that there are ethnic
      differences in the genetic background of IBD. Replication studies by independent
      groups are necessary to elucidate the contribution of susceptibility genes to IBD
      in different ethnic populations.

PMID- 19103526
TI  - TNFA locus is associated with beta degrees 39 thalassemia in Corsica and
      Sardinia.
AB  - Malaria causes more than one million deaths annually, worldwide. Understanding
      the genetic defenses against this disease is an important challenge for science.
      We know that the long-term presence of endemic malaria has led to a prevalence of
      the beta degrees 39 heterozygous thalassemia mutation in the two islands of
      Corsica and Sardinia. The populations of both islands are isolated, which could
      make it easier to find other genetic traits selected by disease pressure. We
      chose to investigate genes implicated in the primary defenses against Plasmodium
      falciparum: oxidative metabolism and the immune response. We indeed selected
      genes coding for nitric oxide synthase 2 (NOS2 promoter, polymorphisms NOS2(AAAT)
      I/D and NOS2(CCTTT)n) and genes coding for tumor necrosis factor-alpha (TNFA
      3'UTR, polymorphisms TNFd(GA)n and TNFe(GA)n). Some associations of TNFA alleles
      or haplotypes were found either with or without the beta degrees 39 mutation,
      suggesting a complex link originally between TNF-alpha and resistance or
      susceptibility to infection.

PMID- 19103527
TI  - Association of two variants of the interferon-alpha receptor-1 gene with the
      presentation of hepatitis B virus infection.
AB  - Interferon-alpha (IFNalpha) is a critical mediator of immunity to hepatitis B
      virus (HBV) infection. Although IFN has been used in the treatment of viral
      hepatitis for more than a decade, the role of IFN-alpha-receptor in HBV infection
      has not been intensively studied. We have evaluated the impact of two variants of
      the IFNAR1 gene on the outcome of HBV infection. Four hundred and fifty eight HBV
      infected Vietnamese patients, with well-characterised clinical profiles including
      all forms of hepatic disease, and 160 non-infected, healthy Vietnamese
      individuals were enrolled in the study. Of these patients, 54 had acute hepatitis
      B, 88 had chronic hepatitis B, 118 had liver cirrhosis, 146 had a hepatocellular
      carcinoma and 52 were asymptomatic carriers of HBV. We analysed two SNPs for
      unequal distribution between these groups. The first SNP, rs1012335 is situated
      in intron 3 of the interferon alpha receptor 1 (IFNAR1). A C at position 17470 in
      the IFNAR1 on both chromosomes was detected more frequently in HBV-infected
      patients compared to healthy controls (OR: 2.6; 95% CI: 1.46-4.72, p < 0.001).
      The same homozygosity is also associated with higher concentrations of AST and
      ALT (aspartate and alanine amino-transferase) in the plasma of the patients. The
      second SNP (rs2257167) is situated in exon 4, causing a change of amino acids
      from Val (GTT) to Leu (CTT). Subjects having GTT on both chromosomes were more
      frequent in the healthy control group (OR: 0.54, 95% CI: 0.35-0.84, p = 0.004)
      and had lower plasma ALT concentrations. The findings indicate that two variants
      of the IFNAR1 gene are associated with the clinical presentation of HBV
      infection.

PMID- 19103528
TI  - Exercise-induced T wave normalization in a patient with stable angina pectoris.

PMID- 19103529
TI  - Spontaneous electrocardiographic changes after syncope in a patient with Brugada
      syndrome: importance of serial ECG recordings.

PMID- 19103530
TI  - The conus artery injection in LAD occlusion.

PMID- 19103532
TI  - Spontaneous pectoral hematoma secondary to enoxaparin for the treatment of deep
      venous thrombosis in an elderly man.

PMID- 19103531
TI  - Catheter-induced multiple spasms in the right coronary artery.

PMID- 19103533
TI  - [Turkey and SSS, AKD's course and corporate trends].

PMID- 19103534
TI  - Obesity and abdominal obesity; an alarming challenge for cardio-metabolic risk in
      Turkish adults.
AB  - OBJECTIVE: To assess the prevalence of obesity and abdominal obesity in Turkish
      adults. METHODS: This is a nationally representative cross-sectional study. From
      both urban and rural areas of seven geographical regions of Turkey 2110 men and
      2154 women with a mean age of 40.9+/-14.9 years (range 20-90) were included in
      this study. Demographic, anthropometric data were collected and biochemical
      analyses of blood lipids and glucose levels were performed in all participants.
      Statistical analyses were performed using Chi-square, unpaired t and two-way
      ANOVA tests. Stepwise logistic regression analysis was applied for the study of
      association of obesity with cardiometabolic risk factors. RESULTS: The prevalence
      of overweight was 36.0% (41.5% in men and 30.6% in women) and the prevalence of
      obesity was 30.4% (20.6% in men and 39.9% in women). The prevalence of obesity
      was similar in rural and urban areas. The prevalence of abdominal obesity and
      metabolic syndrome were 36.2% and 40.9 % according to American Heart, Lung, and
      Blood Institute criteria and 58.7% and 42.6% according to International Diabetes
      Federation criteria, respectively. Abdominal obesity and metabolic syndrome were
      significantly more prevalent among women. After adjusting for age, sex and other
      cardiometabolic risk factors, abdominal obesity was significantly associated with
      increases in body mass index (odds ratio [OR] per 5 kg/m2 increase 1.61, 95% CI
      1.52-1.69) and triglycerides (OR per 10 unit increase 1.02, 95% CI 1.01-1.02) and
      negatively associated with total cholesterol (OR 0.95, 95% CI 0.94-0.96), high
      density lipoprotein cholesterol (OR 0.96, 95% CI 0.93-0.99), systolic blood
      pressure (OR 0.95, 95% CI 0.92-0.98) and diastolic blood pressure (OR 0.94, 95%
      CI 0.90-0.99). CONCLUSION: Obesity and abdominal obesity are major problems for
      Turkish adults, especially for Turkish women. Our finding is alarming for cardio
      metabolic complications and underscores the need for population-based strategies
      to modify lifestyle related risk factors.

PMID- 19103535
TI  - The comparison of the effects of standard 20 mg atorvastatin daily and 20 mg
      atorvastatin every other day on serum LDL-cholesterol and high sensitive C
      reactive protein levels.
AB  - OBJECTIVE: In this study, we aimed at comparing the effects of standard once
      daily 20 mg atorvastatin treatment with that of atorvastatin 20 mg administered
      every other day on serum lipids and high sensitive C-reactive protein (hs-CRP)
      levels. METHODS: Sixty-one patients with serum total cholesterol levels of above
      200 mg/dl and low density lipoprotein (LDL)--cholesterol levels of above 130
      mg/dl were included in this prospective, randomized study. The patients were
      randomized into daily treatment of 20 mg atorvastatin (standard treatment) and 20
      mg atorvastatin every other day (every other day treatment) groups. Before the
      treatment and at each visit, serum lipids and hs-CRP levels of all the patients
      were measured. Statistical analyses were performed Chi-square, unpaired t and two
      way repeated measurements ANOVA tests. RESULTS: In the every other day treatment
      group, there was a 36.1% reduction in LDL-cholesterol levels by the end of first
      month (p<0.01). At the end of three months there was further decrease of 10.2% in
      LDL-cholesterol levels when compared to 1 month levels (p>0.05). The LDL
      cholesterol levels of the group receiving 20 mg atorvastatin every day was
      reduced by %41 by the end of 1 month (p<0.01). At the end of three months, the
      difference between the changes in the all lipid parameters of the two groups was
      not found to be of statistical significance. In the group receiving the
      medication every other day, there was a 21% decrease in hs-CRP levels compared to
      the basal measurements at the end of first month (p<0.05). In the group,
      receiving the medication every day the decrease in hs-CRP levels at the end of
      one month was more striking (37%, p<0.05). However, the effects of both treatment
      arms on hs-CRP levels, did not differ significantly (p>0.05). CONCLUSIONS:
      Alternate-day dosing of atorvastatin causes a significant lipid-lowering and
      antiinflammatory effects similar to that of daily administration and yet may
      provide some cost savings.

PMID- 19103536
TI  - Differences in left ventricular structure, functions and elastance in the
      patients with normotensive blood pressure.
AB  - OBJECTIVE: We aimed in this study to investigate the differences in left
      ventricular (LV) structure, function and elastance parameters in the patients
      with normotensive blood pressure (BP) levels. METHODS: A total of 294
      normotensive patients (<140/90 mmHg) (135 males, mean age: 45+/-11 years; 159
      females, mean age 38+/-10 years) were enrolled into the present cross-sectional
      study. Patients were categorized into three groups according to their BP levels
      as optimal BP (<120/80 mmHg), normal BP (120-129 / 80-84 mmHg) and high normal BP
      (129-139 / 84-89 mmHg) groups. We evaluated LV structure and functions by using
      Doppler echocardiography in all participants. Afterwards we compared the
      measurements for revealing the echocardiographic differences among the BP groups.
      In this study, one-way ANOVA Kruskal-Wallis, one-way ANCOVA and partial
      correlation analysis tests were used for the statistically evaluation of the
      data. In addition, relative risk ratios (RR) were also calculated for
      determination of the effects of BP levels to echocardiographic parameters.
      RESULTS: There were significant statistical differences in left atrial diameter
      (LA) (p=0.002), transmitral A wave velocity (A) (p=0.002), meridional wall stress
      (MWS) (p<0.001), pulmonary capillary wedge pressure (PCW) (p=0.029) among BP
      groups. After the correction of the data for anthropometric measurements,
      multiple comparisons have shown that only end-systolic (Es) and end-diastolic
      elastance (Ed) were different between the normal and high-normal BP groups (for
      Es, p=0.013; for Ed, p=0.007). But it was found that optimal BP group had
      significant differences in LV structure and function parameters when compared to
      high normal BP group (for LA, p=0.028; for A, p=0.035; for MWS, p=0.002; for Es,
      p<0.001; for Ed, p<0.001). Besides, increased RR were detected for increased left
      atrial diameter index and pulmonary capillary wedge pressure values in high
      normal BP group (RR: 1.537, 95% CI (1.197-1.974), p=0.005 and RR: 1.272, 95% CI
      (1.089-1.485), p=0.032, respectively). CONCLUSION: Pathologic changes in LV due
      to increasing BP begin at below-hypertensive BP levels. It could be possible that
      normal BP stage is the beginning level of these changes.

PMID- 19103538
TI  - The acute effect of bi-level positive airway pressure on heart rate variability
      in chronic obstructive pulmonary disease patients with hypercapnic respiratory
      failure.
AB  - OBJECTIVE: Non-invasive mechanical ventilation (NIMV) has the potential to
      improve sympathovagal control of heart rate. The aim of this study was to
      investigate the acute effects of NIMV on heart rate variability (HRV) in chronic
      obstructive pulmonary disease (COPD) patients with hypercapnic respiratory
      failure (HRF). METHODS: In this prospective study 28 COPD patients (64+/-10
      years) with HRF underwent electrocardiographic Holter monitorization. Both time
      domain (TD) and frequency domain (FD) means of HRV analysis were measured for two
      hours before and during NIMV application. For the TD, mean-RR, SDNN, SDANN, SDNN
      index, RMSSD, pNN50 and HRV triangular index were measured. For FD, high
      frequency (HF) and low frequency (LF) were detected. To compare HRV parameters
      before and during bi-level positive airway pressure (BiPAP) application; paired
      sample t test was used for normally distributed variables and Wilcoxon signed
      rank test was used for the variables that were not normally distributed. Pearson
      correlation test was used to analyze the correlation between HRV and blood gas
      parameters during BiPAP application. RESULTS: High frequency power of HRV (39 (18
      65) ms2 vs. 28 (12-50) ms2, p<0.05), HRV triangular index (9 (3-17) units vs. 6
      (2-13) units, p<0.05) and pNN50 (59% (13-110) vs. 42% (5-84), p<0.05), were
      higher during NIMV than before noninvasive mechanical ventilation. CONCLUSIONS:
      We think that NIMV may improve heart rate variability indices of parasympathetic
      modulation of heart rate in COPD cases with HRF and decrease arrhythmic
      potential.

PMID- 19103537
TI  - [The effect of smoking on mean platelet volume and lipid profile in young male
      subjects].
AB  - OBJECTIVE: Smoking and cholesterol levels are two significant causes of
      atherosclerosis. Mean platelet volume (MPV) is an index of platelet activation.
      Only limited numbers of studies showing the effect of smoking on platelet
      function are published. Even less studies exists regarding the effect of smoking
      on platelet function in young healthy population. The current study investigated
      the effects of smoking on the MPV of the young healthy male population. METHODS:
      A total of 102 (smoking 56, nonsmoking 46, medium ages: 22.8) healthy young male
      individuals were included into this cross-sectional study. The subjects with
      hypertension, diabetes, obesity, coroner arterial diseases, lipid metabolism
      disorders, other chronic diseases were excluded. Subjects' waist circumference,
      blood pressure, body mass index (BMI) serum lipid profile and mean platelet
      volume were recorded. Statistical analyses were performed with student t test and
      Pearson correlation analysis. RESULTS: High density lipoprotein(HDL) cholesterol
      levels were lower in smoking group (44.1+/-8.7 mg/dl) compared with nonsmoking
      group (49.7+/-7.6 mg/dl) (p=0.013). Triglyceride levels were higher in smoking
      group (98.6+/-53.0 mg/dl) compared with nonsmoking group (71.5+/-43.0 mg/dl)
      (p=0.041). Very low-density lipoprotein (VLDL) cholesterol levels were also found
      to be higher in smoking group (smoking group: 19.7+/-10.8 mg/dl; nonsmoking
      group: 14.2+/-8.6 mg/dl; p=0.038). However, no significant difference was found
      for MPV between the groups (smoking: 8.57+/-0.8 fl; nonsmoking: 8.67+/-0.8 fl;
      p=0.66) CONCLUSION: The results of the current study revealed higher VLDL
      cholesterol and triglyceride levels and lower HDL-cholesterol levels in smoking
      group and no significant difference was observed for MPV between the smoking and
      nonsmoking young aged healthy male subjects possibly in the early period of
      atherosclerosis.

PMID- 19103539
TI  - Treatment of saphenous vein graft lesions with paclitaxel- and sirolimus-eluting
      stents: comparison of short- and long-term clinical outcomes.
AB  - OBJECTIVE: The purpose of this study was to compare treatment of saphenous vein
      graft (SVG) lesions with paclitaxel-eluting (PES) and sirolimus-eluting stents
      (SES) in daily practice with regard to short- and long-term clinical outcomes.
      METHODS: Between August 2002 and September 2006, a total of 71 patients with SVG
      lesions who were implanted PES or SES with percutaneous coronary intervention in
      our center were evaluated retrospectively. Forty-six patients with PES (PES
      group) were compared to twenty-five patients treated with SES (SES group) in
      terms of in-hospital, 30-day, six-months and 1-year clinical outcomes.
      Statistical analyses were performed using Chi-Square statistics or Fisher's exact
      and independent sample t test. Survival analysis was done using Kaplan-Meier
      method and log-rank test. RESULTS: Baseline clinical characteristics were similar
      in both groups except for a tendency toward a lower age in the SES group. No
      statistically significant difference was found between two groups by means of
      lesion and procedural characteristics. All clinical outcomes at 30-day, 6-month
      and 1-year after the interventions were similar in both groups. Early stent
      thrombosis was detected in one patient (2.2%) of PES group (p=0.65). Late stent
      thrombosis was not observed in both groups. The rate of major adverse cardiac
      events at 1-year was 8.7% in the PES group and 16% in the SES group (p=0.44).
      CONCLUSION: Short-and long-term clinical outcomes of PES and SES in the treatment
      of SVG lesions are similar. The results of our study showed that both drug
      eluting stents are effective and safe in real-world patient with diseased SVGs.

PMID- 19103540
TI  - The effects of low dose N-acetylcysteine (NAC) as an adjunct to cardioplegia in
      coronary artery bypass surgery.
AB  - OBJECTIVE: We aimed to evaluate the efficacy of low dose N-acetylcysteine (NAC)
      against myocardial ischemia-reperfusion damage in coronary artery bypass surgery
      accompanied by cardiopulmonary bypass (CPB). METHODS: Thirty patients operated
      due to triple coronary artery disease were enrolled into this prospective
      randomized study (control group -n=15 and NAC group - n=15). N-acetylcysteine was
      added to induction cardioplegia solution in dose of 4 mmol/l and in dose of 2
      mmol/l to maintenance cardioplegia solution in the NAC group. Hemodynamic
      measurements were performed before and after anesthesia with different intervals.
      Creatine kinase-MB (CK-MB) levels were analyzed during 24 hours postoperatively.
      Blood samples were obtained from coronary sinus before CPB (T1), just before the
      cross-clamp removed (T2) and 30 minutes later (T3). Malondialdehyde (MDA),
      glutathione peroxidase (GSH-Px), nitric oxide (NO) levels and neutrophil
      percentage were determined. Statistical analysis was performed using student's t
      test, Chi-square and two-way ANOVA tests. RESULTS: There were no significant
      differences between the two groups with regard to the hemodynamic parameters, and
      CK-MB levels. The MDA levels were significantly lower in NAC group than in
      control group during reperfusion period (0.75 nmol/l vs 0.88 nmol/l, p<0.05).
      Neutrophil percentage in coronary sinus blood was significantly lower in NAC
      group than in control group during the reperfusion period (77.6% vs 82.7%,
      p<0.05). The GSH-Px and NO levels were also not statistically different between
      groups. CONCLUSION: Low dose NAC as an adjunct to cardioplegic solutions
      effectively reduces myocardial oxidative stress in coronary bypass surgery with
      cardiopulmonary bypass, but may not restore the myocardial injury.

PMID- 19103542
TI  - Diagnosis and treatment options for the infrapopliteal peripheric arterial
      occlusive diseases.

PMID- 19103541
TI  - Bypass grafting for infrapopliteal occlusive disease with poor distal flow on
      angiography.
AB  - OBJECTIVE: We aimed to investigate whether limb-salvage bypass operation improves
      outcomes in patients with critical infrapopliteal ischemia and poor or no distal
      arterial flow on angiography. METHODS: Forty-nine patients with severe tibial and
      peroneal occlusive disease and poor distal arterial flow on angiography were
      included in this prospective study. The age ranged from 57 to 82 years in the
      surgical group and 63 to 80 in the medical group. Patients had class III or IV
      disease according to Fontaine classification. Preoperative arterial Doppler
      ultrasonography and arteriography were performed in all patients. The ankle
      brachial index (ABI) was calculated preoperatively and postoperatively in all of
      the cases. Twenty-three patients underwent distal bypass operation. Other 26
      patients were followed with medical therapy. The outflow distal anastomoses were
      performed on posterior tibial, dorsal pedal, anterior tibial, peroneal, and
      lateral plantar arteries. All patients were followed-up for 3 years and clinical
      outcomes were recorded. The statistical analyses were performed using unpaired t,
      Mann Whitney and Wilcoxon tests. RESULTS: There were 3 early and 2 late graft
      failures. Limb salvage rates were 84.2%, 84.2%, 73.7% in the surgical group, and
      82.8%, 69.9%, 64.3% in the medical group respectively in 6 months, 1 year, and 3
      years. According to statistical analysis; the levels of the amputations tend to
      be lower in the surgical group than in the medical group but it was not
      significant statistically. Surgical treatment reduced the amputation ratio
      (p<0.05) but medical therapy did not (p>0.05). The difference between
      preoperative mean ABI [0.26+/-0.06] and postoperative mean ABI [0.80+/-0.24] was
      significant (p<0.05). CONCLUSION: We think that limb-salvage bypass operation may
      be preferred for patients with critical limb ischemia and poor distal flow on
      angiography. Infrapopliteal bypass will provide limb salvage and a functional
      extremity.

PMID- 19103543
TI  - [Intrinsic cardiac ganglia].
AB  - Heart has been considered as the source and the seat of emotions, passion and
      love. But from the dawn of XIXth century, scientists have emphasized that the
      heart, though life depends on its ceaseless activity, is merely a
      electromechanical pump, pumping oxygenated blood. Nowadays, we all know that
      heart pumps blood commensurate with the needs of the body and this unending toil,
      and its regulation depends on the intrinsic properties of the myocardium, Frank
      Starling Law and neurohumoral contribution. It has been understood, though not
      clearly enough, that these time-tensions may cause structural or functional
      cardiac impairments and arrhythmias are related to the autonomic nervous system.
      Less well known and less taken in account in daily cardiology practice is the
      fact that heart has an intrinsic cardiac nervous system, or "heart brain"
      consisting of complex ganglia, intrinsic cardiac ganglia containing afferent
      (receiving), local circuit (interneurons) and efferent (transmitting) sympathetic
      and parasympathetic neurons. This review enlightens structural and functional
      aspects of intrinsic cardiac ganglia as the very first step in the regulation of
      cardiac function. This issue is important for targets of pharmacological
      treatment and techniques of cardiac surgery interventions as repair of septal
      defects, valvular interventions and congenital corrections.

PMID- 19103544
TI  - Coronary angiography in a patient with situs inversus and dextrocardia.

PMID- 19103545
TI  - Successful deployment of an atrial septal occluder device in a patient with an
      insufficient posterosuperior defect rim.

PMID- 19103546
TI  - Anomalous right coronary artery arising from the distal left circumflex coronary
      artery.

PMID- 19103547
TI  - The effects of internal thoracic artery preparation with intact pleura on
      respiratory function and patients' early outcomes.

PMID- 19103548
TI  - Re-operation for the mechanical valve obstruction with a beating heart technique
      in an elderly patient with compromised ventricular function.

PMID- 19103549
TI  - Skeletonized internal thoracic artery/ The effects of internal thoracic artery
      preparation with intact pleura on respiratory function and patients' early
      outcomes.

PMID- 19103550
TI  - [Vasospastic angina mimicking inferior myocardial infarction due to high dose
      cyclophosphamide for bone marrow transplantation conditioning].

PMID- 19103551
TI  - [A gold standard method for early detection of transplant vasculopathy after
      heart transplantation: intravascular ultrasound].

PMID- 19103552
TI  - Paget-Schroetter syndrome.

PMID- 19103553
TI  - [A case of aortic dissection in an adolescent with Marfan syndrome and surgical
      treatment].

PMID- 19103554
TI  - Problems of high-altitude medicine in Kyrgyz Republic: in memory of Professor
      Mirsaid M. Mirrakhimov.

PMID- 19103557
TI  - [Neoadjuvant systemic therapy in breast cancer].
AB  - Neoadjuvant (preoperative) systemic therapy is a good possibility for the
      treatment of symptomatic breast cancers of the locoregional stage. Chemotherapy
      or hormone therapy chosen according to the characteristics of the primary tumor,
      result in the regression of the tumor in the majority of the cases, favoring
      breast conserving surgery thereafter. The long-term effects of neoadjuvant
      systemic therapy are equivalent to that of adjuvant therapy, and the in vivo
      observed efficiency of the treatment reflects prognosis. Finally, systemic
      therapy introduced prior to surgery is not delayed by the possible adverse
      effects of the surgery. Detailed examination of the tumor and the patient is
      mandatory before starting systemic therapy. Besides breast imaging and
      histological examinations, staging is necessary. Pathological characterization of
      the tumor will enhance treatment choice based on the features of chemo- or
      hormone-sensitivity. For the treatment of chemosensitive tumors, taxane- and
      anthracycline-based polychemotherapy is the most efficacious. Data on neoadjuvant
      hormone therapy have been provided by studies on postmenopausal patients. Since
      the aromatase inhibitors are more efficient than tamoxifen, their use is the
      first option in this patient population. Among the molecular targeted agents,
      trastuzumab combined with chemotherapy produces extending therapeutic response
      rate. Following the completion of the neoadjuvant systemic therapy, breast
      imaging is required once more before performing breast and lymph node surgery.
      Postoperative radiotherapy is generally needed. The use of a common language and
      professional guidelines by the members of the multidisciplinary breast team is a
      condition for neoadjuvant systemic therapy.

PMID- 19103556
TI  - [From free radicals to science of nutrition].
AB  - During the decades of free radical research, we came ever closer to the knowledge
      that the free radical-antioxidant balance of the organs is modified fundamentally
      by the genetic background and surroundings. Janus-face oxygen free radicals are
      the secondary messengers of signal transduction routes and simultaneously they
      are cytotoxic agents of cells. The activation of signal transduction proteins by
      moderate oxidation effects and metal ions is not fairly known yet. The molecular
      mechanism between activators and inhibitors of signal transduction is controlled
      in a fine way. The balance of antioxidant-prooxidant levels of the cells can go
      back to the concentration relation of sulfhydril groups and disulfid bridges.
      Essential and toxic metal ions and selenium can play an important role in the
      redox homeostasis. Healthy tissues have many antioxidants, hereby they ensure the
      protection of the organs against free radicals. Alimentary antioxidants such as
      vitamin A, C and E, polyphenols, anthocyanins, flavonoids, isothiocyanates and
      other bioactive molecules in their natural molecular structure and derivates are
      able to influence the redox reactions. In our days more and more molecules from
      foods, or their metabolites are verified to act on genes based on the results of
      molecular biological research.

PMID- 19103558
TI  - [Effects of supplementation with the antioxidant flavonoid, silymarin, in chronic
      hepatitis C patients treated with peg-interferon + ribavirin. A placebo
      controlled double blind study].
AB  - Since oxidative stress may play a pathogenetic role in chronic hepatitis C, and
      sustained virological response to antiviral therapy is limited in HCV1 genotype
      infection, a double blind study was performed in HCV1 patients treated with
      pegylated interferon + ribavirin, to assess the efficacy of supplementation with
      the antioxidant flavonoid silymarin. PATIENTS AND METHODS: Thirty-two naive HCV1
      positive patients with biopsy proven chronic hepatitis C, to be treated with
      pegylated interferon + ribavirin, have been randomized: group A): 16 patients
      have been given the antiviral therapy for 6-12 months plus placebo for the first
      3 months; group B): 16 patients have been treated with pegylated interferon +
      ribavirin for 6-12 months plus silymarin, 2 x 166 mg/day, was given for 3 months.
      Serum alanine aminotransferase and HCV-RNA levels as well as parameters of
      oxidative stress such as plasma or red blood cell hemolysate, malondialdehyde,
      superoxide dismutase, glutathione peroxidase, catalase and myeloperoxidase were
      determined after 0, 1, 3, 6 and 12 months during the treatment. Sustained
      virological response as undetectable serum HCV RNA was evaluated 24 weeks after
      the end of therapy. RESULTS: In the silymarin group, a more rapid decrease in the
      malondialdehyde level as well as a marked decrease in superoxide dismutase and an
      increase in myeloperoxidase activity after month 12 were found, alanine
      aminotransferase normalized in 6/16 (vs control 9/16) cases, and sustained
      virological response occurred in 3/16 (vs 7/16) patients. DISCUSSION/CONCLUSION:
      Although silymarin supportation to antiviral therapy improved oxidative stress,
      it was able to affect favourably neither the alanine aminotransferase nor the
      sustained virological response. These contradictory findings may be related to
      randomization bias as patients in study group B had more negative predictors of
      response: they were older with higher fibrosis score and even with more severe
      pretreatment baseline oxidative stress. Regarding the recently published in vitro
      experiments with silybinin on HCV replication as well as the newest convincing
      clinical observations, we do suggest further studies with more than three times
      higher doses of silymarin in controlled trials to assess the value of this
      supplementation in antivirally treated HCV patients.

PMID- 19103559
TI  - [Susceptibility genetic variants in Hungarian morbus Crohn and ulcerative colitis
      patients].
AB  - We examined several susceptibility genetic variants to inflammatory bowel disease
      (Crohn's disease, ulcerative colitis) in Hungarian population, such as the CARD15
      R702W, G908R, 1007finsC genetic variants, the SLC22A4 C1672T and SLC22A5 G-207C
      variants and their determined TC haplotype, the CTLA4 gene A+49G genetic variant
      and the rs10889677 C/A, rs2201841 T/C, rs1884444 G/T variants of the IL23R gene.
      We examined 201 adult patients with Crohn's disease, 241 adult patients with
      ulcerative colitis and 19 pediatric patients with Crohn's disease. For control
      235 adult and 49 pediatric subjects were used. The genotyping was carried out
      using PCR/RFLP methods and direct sequencing. From the CARD15 gene mutations in
      the adult Crohn's disease population the 1007finsC, while in the pediatric
      population the 1007finsC and the G908R were significantly associated with an
      increased risk for Crohn's disease. We found no significant differences comparing
      the results of the patients and the controls by the SLC22A4, SLC22A5 genetic
      variants and the TC haplotype. The A+49G variant of the CTLA4 gene was not an
      independent determinant to inflammatory bowel disease. We found that the IL23R
      gene variants, rs10889677 C/A and rs2201841 T/C appear to increase susceptibility
      to Crohn's disease. It depends on the different populations whether this genetic
      variant means an obligatory risk factor to inflammatory bowel disease.

PMID- 19103560
TI  - [Centenary of a Semmelweis memorial in Budapest, Hungary].

PMID- 19103562
TI  - Use of chemometrics for development and validation of an RP-HPLC method for
      simultaneous determination of haloperidol and related compounds.
AB  - A rapid resolution reversed-phase high performance liquid chromatographic (RR RP
      HPLC) method has been developed and validated for simultaneous determination of
      haloperidol and six related compounds. Investigated matrix was a laboratory
      mixture of a therapeutic active substance haloperidol and its six related
      compounds in concentration ratio 300:1. Experimental design was used during
      method optimization (full factorial 23 design) and robustness testing (Central
      Composite Circumscribed design). Three factors: organic phase variation during
      gradient elution, flow rate and gradient rise time were independent variables. To
      estimate the system response during the optimization procedure and robustness
      testing, resolution (Rs) and a chromatographic response function (CRF) were used.
      Chromatography was performed with the mobile phase containing phosphate buffer pH
      6.5 and acetonitrile as organic modifier. Separation was achieved using gradient
      elution (organic phase fraction changed linearly from 20 to 72 %) over 7 min. A
      Zorbax Eclipse XDB C18 Rapid Resolution HT 4.6 mm x 50 mm, 1.8 mum particle size,
      column was used at 25 degrees C at a flow rate of 1.5 mL min-1. UV detection was
      performed at 230 nm. The total time for chromatographic separation was 5.5 min
      with a total analysis time of 7.0 min. The method was validated for its
      linearity, precision, modal recovery and robustness.

PMID- 19103563
TI  - Improved dissolution of a poorly water soluble drug in solid dispersions with
      polymeric and non-polymeric hydrophilic additives.
AB  - Irbesartan (IBS) is a hydrophobic drug with poor aqueous solubility and
      dissolution rate. Solid dispersions (SDs) of IBS were prepared with both small
      molecules (tartaric acid and mannitol) and polymeric additives (polyvinyl
      pyrrolidone, PVP, and hydroxypropyl methylcellulose, HPMC). A 9.5 and 7 folds
      enhancement in solubility over the crystalline form (14.6 microg mL-1) was
      observed for tartaric acid (138 microg mL-1) and PVP (103 microg mL-1),
      respectively. Powder X-ray diffraction confirmed that IBS existed in the glassy
      state in all cases, even with excipients having low glass transition temperature.
      Thermal methods (differential scanning calorimetry and hot stage microscopy) were
      used to evaluate the miscibility of the drug and additives. These techniques
      suggested that tartaric acid led to generation of >>amorphous solutions<< in
      contrast to >>amorphous suspensions<< in other three cases. The in vitro
      dissolution of IBS depended on the additive load and increased with increasing
      concentration in the case of tartaric acid, an acidifying excipient. The results
      indicate the suitability of even small molecules for providing solubility
      benefits, which can be attributed to the good glass forming ability and
      reasonable ability of IBS to remain in the glassy state.

PMID- 19103564
TI  - Development and validation of spectrophotometric methods for determination of
      ceftazidime in pharmaceutical dosage forms.
AB  - Two spectrophotometric methods for the determination of ceftazidime (CFZM) in
      either pure form or in its pharmaceutical formulations are described. The first
      method is based on the reaction of 3-methylbenzothiazolin-2-one hydrazone (MBTH)
      with ceftazidime in the presence of ferric chloride in acidic medium. The
      resulting blue complex absorbs at lambdamax 628 nm. The second method describes
      the reaction between the diazotized drug and N-(1-naphthyl)ethylenediamine
      dihydrochloride (NEDA) to yield a purple colored product with lambdamax at 567
      nm. The reaction conditions were optimized to obtain maximum color intensity. The
      absorbance was found to increase linearly with increasing the concentration of
      CFZM; the systems obeyed the Beer's law in the range 2-10 and 10-50 microg mL-1
      for MBTH and NEDA methods, resp. LOD, LOQ and correlation coefficient values were
      0.15, 0.79 and 0.50, 2.61. No interference was observed from common excipients
      present in pharmaceutical formulations. The proposed methods are simple,
      sensitive, accurate and suitable for quality control applications.

PMID- 19103565
TI  - A study of rivastigmine liposomes for delivery into the brain through intranasal
      route.
AB  - The present study is mainly aimed at delivering a drug into the brain via the
      intranasal route using a liposomal formulation. For this purpose, rivastigmine,
      which is used in the management of Alzheimer's disease, was selected as a model
      drug. Conventional liposomes were formulated by the lipid layer hydration method
      using cholesterol and soya lecithin as lipid components. The concentration of
      rivastigmine in brain and plasma after intranasal liposomes, free drug and per
      oral administration was studied in rat models. A significantly higher level of
      drug was found in the brain with intranasal liposomes of rivastigmine compared to
      the intranasal free drug and the oral route. Intranasal liposomes had a longer
      half-life in the brain than intranasally or orally administered free drug.
      Delivering rivastigmine liposomes through the intranasal route for the treatment
      of Alzheimer's disease might be a new approach to the management of this
      condition.

PMID- 19103566
TI  - Stability of amlodipine besylate and atenolol in multi-component tablets of mono
      layer and bi-layer types.
AB  - Multi-drug tablets of amlodipine besylate and atenolol were prepared as either
      mono-layer (mixed matrix) or bilayer tablets containing each drug in a separate
      layer by using similar excipients and processing. Each tablet batch was packed in
      strip and blister packs and kept under accelerated temperature and humidity
      conditions. The stability of two tablet and packaging types was compared by HPLC
      analysis after 0, 1, 3 and 4.5 months and expressed as the content of intact
      amlodipine and atenolol. The content of atenolol did not decline regardless of
      tablet and packaging type. Amlodipine content in bi-layer tablets decreased to
      about 95 and 88% when packed in strips and blisters, respectively. When prepared
      as mono-layer tablets, the content decreased to 72 and 32%, respectively.The
      study revealed that the bi-layer tablet formulation was more stable than the mono
      layer type. Further, the stability was increased when the tablets were packed in
      aluminium strips as compared to PVC blisters.

PMID- 19103567
TI  - Preparation and evaluation of an ispaghula based directly compressible matrixing
      agent for controlled release.
AB  - The objective of the present investigation was to prepare and evaluate an
      ispaghula husk based directly compressible (DC) adjuvant that can be used as
      matrixing agent using an agglomeration technique. Addition of hydroxypropyl
      methylcellulose was found necessary to improve cohesion. Lactose (X1), calcium
      hydrogen phosphate dihydrate (X2) and Avicel PH101 (X3), used along with
      ispaghula in preparation of agglomerates, were selected as three independent
      variables in a simplex lattice design affecting compressional and dissolution
      characteristics of the drug from the DC adjuvant. The agglomerates were evaluated
      for their flow properties. Tablets were prepared using 70% agglomerates and 30%
      acetaminophen, a poorly compressible drug, and were subjected to in vitro drug
      release study. Amounts of the drug released at the end of 60 min (Y60), 300 min
      (Y300) and 480 min (Y480) were selected as dependent variables in a simplex
      lattice design. Batch IH05 that contained lactose and calcium hydrogen phosphate
      dihydrate in a 1:2 ratio could control the release for 12 hours and thus form the
      basis for twice a-day-dosing.

PMID- 19103568
TI  - 2-Amino-5-sulfanyl-1,3,4-thiadiazoles: a new series of selective cyclooxygenase-2
      inhibitors.
AB  - A new series of cyclooxygenase-2 inhibitors with 2-amino-5-sulfanyl-1,3,4
      thiadiazole as the central scaffold unit has been synthesized. The newly
      synthesized compounds were characterized by analytical and spectral methods.
      Compounds were screened for cyclooxygenase inhibitory activity by the
      colorimetric COX (ovine) inhibitor screening assay, anti-inflammatory activity by
      the carrageenean induced rat paw oedema test and analgesic activity by the tail
      flick method. Some compounds exhibited significant biological activity.

PMID- 19103569
TI  - Selective determination of Fe(III) in Fe(II) samples by UV-spectrophotometry with
      the aid of quercetin and morin.
AB  - Selective UV-spectrophotometric methods for determination of iron(III) in
      iron(II) samples have been developed. The methods are based on the interaction of
      Fe(III) with quercetin and morin, compounds of the flavonoid group. Redox
      reactions occurring between Fe(III) ions and the reagents used make the basis for
      the detection. Iron(II) does not react with quercetin and morin under the
      conditions applied [aqueous-methanolic (3:2) soluions, 0.3 mol L(-1) HCl, 1.2 x
      10(-4) mol L(-1) quercetin (morin)] and does not interfere with the determination
      of Fe(III). Iron(III) can be determined up to 15 microg mL(-1) using both the
      examined systems. The detection limits are 0.06 and 0.38 microg mL(-1) when using
      quercetin or morin, respectively. The method with quercetin was applied to the
      determination of Fe(III) (ca. 0.2%) in a Fe(II) pharmaceutical product.

PMID- 19103570
TI  - 3D-QSAR studies for the binding affinity toward (R, S)-2-amino-3-(3-hydroxy-5
      methylisoxazol-4-yl)-propionic acid receptor.
AB  - An approach for binding affinity evaluation is suggested and exemplified using a
      set of triazolo [1,5-a] quinoxaline for the (R, S)-2-amino-3-(3-hydroxy-5
      methylisoxazol-4-yl)-propionic acid (AMPA) receptor. Biological activity toward
      the AMPA receptor (expressed as -log IC50) was taken as a dependent variable for
      building Comparative Molecular Field Analysis (CoMFA) and Comparative Molecular
      Similarity Indices Analysis (CoMSIA) models. The resulting models show the ways
      of increasing the binding affinity to the AMPA receptor as a potential target for
      epilepsy. The statistically significant results show that the cross-validated
      r2CV value (0.766) for the CoMFA model is greater than (0.758) for the CoMSIA
      model. The non-cross validated run giving the coefficient of determination r2
      values of 0.944 and 0.919 for CoMFA and CoMSIA, respectively, provided good
      correlation between the observed and computed affinities of the training set
      compounds. The resulting CoMFA and CoMSIA models indicate that steric,
      electrostatic, hydrophobic (lipophilic), hydrogen bond donor and acceptor
      substituents play a significant role in increasing the binding affinity and
      selectivity of the compounds toward the AMPA receptor.

PMID- 19103571
TI  - Gradient HPLC analysis of raloxifene hydrochloride and its application to drug
      quality control.
AB  - A rapid, sensitive and selective method for the determination of raloxifene
      hydrochloride (RLX) in pure drug and in tablets was developed using gradient high
      performance liquid chromatography (HPLC). The devised method involved separation
      of RLX on a reversed phase Hypersil ODS column and determination with UV
      detection at 284 nm. The standard curve was linear (R = 0.999) over the
      concentration range of 50-600 microg mL-1 with a detection limit of 0.04 microg
      mL-1 and a quantification limit of 0.16 microg mL-1. Intra-day and inter-day
      precision and accuracy of the method were established according to the current
      ICH guidelines. Intra-day RSD values at three QC levels (250, 450 and 550 microg
      mL-1) were 0.2-0.5%, based on the peak area. The intra-day relative error (er)
      was between 0.2 and 0.5%. The developed method was successfully applied to the
      determination of RLX in tablets and the results were statistically compared with
      those obtained by a literature method. Accuracy, evaluated by means of the spike
      recovery method, was the excellent with percent recovery in the range 97.7-103.2
      with precision in the range 1.6-2.2%. No interference was observed from the co
      formulated substances. The method was economical in terms of the time taken and
      the amount of solvent used.

PMID- 19103572
TI  - Synthesis and evaluation of analgesic, anti-inflammatory and ulcerogenic
      activities of some triazolo- and 2-pyrazolyl-pyrido[2,3-d]-pyrimidines.
AB  - New series of 2-hydrazino-7,8-dihydro-6H-cyclopenta[5,6] pyrido[2,3-d]pyrimidines
      and its 1,7,8,9-tetrahydrocyclopenta[5,6]pyrido[2,3-d][1,2,4]triazolo[4,3
      a]pyrimidine, 1,7,8,9-tetrahydrocyclopenta[5,6]pyrido[2,3
      d][1,2,3,4]tetrazolo[4,5-a]pyrimidine, 8,9-dihydro-7H-cyclopenta[5,6]pyrido[2,3
      d]imidazolo[1,2-a]pyrimidine, 2-(pyrazol-1-yl)-7,8-dihydro-6H
      cyclopenta[5,6]pyrido[2,3-d]pyrimidine derivatives were prepared in order to
      obtain new compounds with potential anti-inflammatory and analgesic activity and
      low ulcerogenic effect. The compounds possessing potent anti-inflammatory
      activity were further tested for their analgesic and ulcerogenic activities.
      Compounds 3-amino-6-(4-aryl)-9-(4-arylmethylene)-cyclopenta[5,6]pyrido[2,3
      d][1,2,4]triazolo[4,3-a]pyrimidin-5(H)-one (4c), 1-amino-2-methyl-6-(4-aryl)-9-(4
      aryl-methylene)-cyclopenta[5,6]pyrido[2,3-d]imidazolo[1,2-a]pyrimidin-5(H)-one
      (6a), 2-amino-5-(4-aryl)-8-(4-arylmethylene)-cyclopenta[5,6]pyrido-[2,3
      d]pyrimidine-4(H)-one (9), 2-(3-amino-5-hydroxypyrazol- 1-yl)-5-(4-aryl)-8-(4
      arylmethylene)-cyclopenta[5,6]-pyrido[2,3-d]pyrimidin-4(H)-one (10a) and 3-thioxo
      6-(4-aryl)-9-(4-arylmethylene)-cyclopenta[5,6]pyrido[2,3-d]-[1,2,4]triazolo[4,3
      a]pyrimidin-5(H)-one (13) showed significant analgesic effects. Compound 2-(3
      amino-5-hydroxypyrazol-1-yl)-5-(4-aryl)-8-(4-arylmethylene)-cyclopenta
      [5,6]pyrido[2,3-d]pyrimidin-4(H)-one (10a) was evaluated as the lead compound
      having higher anti-inflammatory activity (82.8%) than ibuprofen (79.5%) and lower
      ulcerogenic effect.

PMID- 19103573
TI  - Design and optimization of artemether microparticles for bitter taste masking.
AB  - The objective of the present investigation was to reduce the bitterness of
      artemether (ARM). Microparticles were prepared by the coacervation method using
      Eudragit E 100 (EE) as polymer and sodium hydroxide solution as nonsolvent for
      the polymer. A 32 full factorial design was used for optimization wherein the
      amount of drug (A) and polymer (B) were selected as independent variables and the
      bitterness score, particle size and drug release at pH, 1.2 and 6.8 were selected
      as dependent variables. Optimization was carried out using the desirability
      function. The optimized microparticles batch was characterized by FTIR and DSC.
      Multiple linear regression analysis revealed that reduced bitterness of ARM can
      be obtained by controlling the drug release of microparticles at pH 6.8 and
      increasing the amount of EE. The increase in the amount of polymer leads to
      reduction in drug release from microparticles at pH > 5 due to its insolubility
      and thus reduces bitterness. However, the increase in the amount of polymer
      results in improved dissolution, suggesting improved availability of ARM in
      stomach. Optimized microparticles prepared using 0.04 g of ARM and 15 mL of 1%
      (m/V) solution of EE showed complete bitter taste masking with improved drug
      release at pH 1.2.

PMID- 19103574
TI  - Synthesis and evaluation of 2-substituted-6-phenyl-4,5-dihydropyridazin-3(2H)
      ones as potent inodilators.
AB  - The present study describes the synthesis and pharmacological evaluation of 2
      substituted-6-(4-acylaminophenyl)-4,5-dihydropyridazin-3(2H)-ones as potent
      inodilating agents. The synthesis of target compounds 2-4 and 7-11 was achieved
      by Friedel-Crafts acylation of appropriate anilide derivative with succinic
      anhydride or methylsuccinic anhydride and subsequent cyclization of intermediary
      keto acids with various hydrazine derivatives. The newly synthesized pyridazinone
      derivatives were evaluated for cardiotonic activity using isolated rat atria and
      for vasorelaxant activity using descending thoracic aortic rings of Wistar rats
      precontracted with phenylephrine (10-6 mol L-1). 6-(4-Methanesulfonamidophenyl)-2
      phenyl-4,5-dihydropyridazin-3(2H)-one (7) exhibited significant inodilatory
      properties and showed vasorelaxant activity in a nanomolar range (IC50 = 0.08 +/-
      0.01 mumol L-1).

PMID- 19103575
TI  - Development and in vitro evaluation of an acid buffering bioadhesive vaginal gel
      for mixed vaginal infections.
AB  - An acid buffering bioadhesive vaginal (ABBV) gel was developed for the treatment
      of mixed vaginal infections. Different bioadhesive polymers were evaluated on the
      basis of their bioadhesive strength, stability and drug release properties.
      Bioadhesion and release studies showed that guar gum, xanthan gum and
      hydroxypropyl methylcelullose K4M formed a good combination of bioadhesive
      polymers to develop the ABBV gel. Monosodium citrate was used as an acid
      buffering agent to provide acidic pH (4.4). The drugs clotrimazole (antifungal)
      and metronidazole (antiprotozoal as well as antibacterial) were used in the
      formulation along with Lactobacillus spores to treat mixed vaginal infections.
      The ex vivo retention study showed that the bioadhesive polymers hold the gel for
      12-13 hours inside the vaginal tube. Results of the in vitro antimicrobial study
      indicated that the ABBV gel had better antimicrobial action than the commercial
      intravaginal drug delivery systems and retention was prolonged in an ex vivo
      retention experiment.

PMID- 19103576
TI  - Protective role of the calcium channel blocker amlodipine against mitochondrial
      injury in ischemia and reperfusion injury of rat liver.
AB  - Ca2+ accumulation and Ca2+ overloading in mitochondria are responsible for the
      cell abnormality associated with ischemia and reperfusion injury. The present
      study was aimed at evaluating the efficacy of the Ca2+ channel blocker amlodipine
      on the mitochondrial Ca2+ accumulation, mitochondrial antioxidant status and
      mitochondrial respiratory enzymes in ischemia and reperfusion (I/R) induced liver
      injury. I/R injury induced mitochondrial damage in rats was assessed in terms of
      the decrease in activities (p < 0.05) of respiratory marker enzymes (malate
      dehydrogenase, succinate dehydrogenase and NADH dehydrogenase), mitochondrial
      antioxidant enzymes (glutathione, superoxide dismutase, catalase), and
      significant increase (p < 0.05) in the level of lipid peroxidation (LPO) and Ca2+
      content.Mitochondrial damage was confirmed by transmission electron microscopic
      (TEM) examination. Pretreatment with amlodipine effectively counteracted the
      alteration in mitochondrial enzymes induced by ischemia-reperfusion liver damage.
      TEM study confirms the restoration of cellular normalcy and the cytoprotective
      role of amlodipine against I/R induced hepatic injury. On the basis of our
      findings it may be concluded that amlodipine not only possesses Ca2+ channel
      antagonist properties but it may also reduce the extent of mitochondrial damage
      by its antioxidant activity.

PMID- 19103577
TI  - The reaction of beta-amino-alpha,gamma-dicyanocrotononitrile with acetophenone:
      synthesis of pyridine, pyridazine and thiophene derivatives with antimicrobial
      activities.
AB  - Condensation of beta-amino-alpha,gamma-dicyanocrotononitrile (1) with
      acetophenone gave 2-amino-4-phenylpenta-1,3-diene-1,1,3-tricarbonitrile (2). The
      latter product was used in a series of heterocyclization reactions with different
      reagents such as diazonium salts, hydrazines, hydroxylamines and elemental sulfur
      to give pyridazine, pyrazole, isoxazole and thiophene derivatives, respectively.
      On the other hand, it gave pyridine derivatives with aromatic aldehydes folowed
      by reaction with cyanomethylene reagents. The MIC values for the newly
      synthesized product were measured against E. coli, B. cereus, B. subtilis and C.
      albicans.

PMID- 19103578
TI  - Synthesis, anticonvulsant and toxicity evaluation of 2-(1H-indol-3-yl)acetyl-N
      (substituted phenyl)hydrazine carbothioamides and their related heterocyclic
      derivatives.
AB  - A series of new 5-(1H-indol-3-yl)methyl-4-(substituted aryl)-2,4-dihydro-3H-1,2,4
      triazole-3-thiones (4a-g), 5-(1H-indol-3-yl)methyl-N-(substituted aryl)-1,3,4
      oxadiazol-2-amines (5a-g) and 5-(1H-indol-3-yl)methyl-N-(substituted aryl)-1,3,4
      thiadiazol-2-amines (6a-g) were prepared by treating 2-(1H-indol-3-yl)acetyl-N
      (substituted phenyl) hydrazine carbothioamides (3a-g) with suitable reagents. All
      the newly synthesized compounds were screened for their anticonvulsant activity
      in the MES model and were compared with the standard drugs phenytoin sodium and
      carbamazepine. Out of the twenty-one compounds studied, 4b, 4e, 4f, 5b, 5d, 5g,
      6b, 6d and 6e showed comparable MES activity to phenytoin and carbamazepine after
      0.5 h. Compound 5b showed to be more potent than carbamazepine after 4 h.
      Compounds 4a, 4c, 4d, 5a, 5c, 5e, 5f, 6f and 6g showed lower neurotoxicity than
      phenytoin.

PMID- 19103579
TI  - Characterization of ternary complexes of meloxicam-HPbetaCD and PVP or L-arginine
      prepared by the spray-drying technique.
AB  - Ternary complexes of meloxicam (ME) (a poorly water soluble anti-inflammatory
      drug) with hydroxypropyl-beta-cyclodextrin (HPbetaCD) and either a hydrophilic
      polymer, namely, polyvinyl pyrrolidone (PVP) or a basic amino acid such as L
      arginine, were prepared by the spray-drying technique. The solubilizing
      efficiency, physical properties and dissolution behaviour of each ternary system
      of ME-HPbetaCD with either PVP or L-arginine were compared with those of the
      corresponding binary system of ME-HPbetaCD. Tablets compressed from the ternary
      system of ME-HPbetaCD-L-arginine were compared with plain and commercial tablets.
      Phase solubility experiments suggested the formation of an inclusion complex of
      AL type. Ternary system of ME-HPbetaCD-L-arginine exhibited a stability constant
      30.3 times higher than the binary system of ME-HPbetaCD, while the ternary system
      of ME-HPbetaCD-PVP increased the stability constant 2.2 times only. The prepared
      complexes were characterized by scanning electron microscopy, differential
      scanning calorimetry and infra red spectroscopy. Ternary solid complexes
      indicated the presence of strong interactions between the components. The
      dissolution behaviour of ME from different ternary complexes was higher than its
      dissolution from the binary system. Tablets compressed from ternary complexes of
      ME-HPbetaCD-L-arginine highly improved drug release compared to plain and
      commercial tablets.

PMID- 19103580
TI  - Synthesis and biological evaluation of some 4-(1H-indol-3-yl)-6-phenyl-1,2,3,4
      tetrahydropyrimidin-2-ones/thiones as potent anti-inflammatory agents.
AB  - Twelve new 4-(1H-indol-3-yl)-6-phenyl-1,2,3,4-tetrahydropyrimidin-2-ones/thiones
      (7-18) have been synthesized by reacting 1-aryl-3-(1H-indol-3-yl)-2-propen-1-one
      with urea and thiourea in ethanolic potassium hydroxide. Their structures have
      been confirmed by IR, 1H NMR and mass spectral data. The compounds were tested
      for their anti-inflammatory activity. Test results revealed that compounds showed
      49.5 to 70.7% anti-inflammatory activity where-as the standard drug ibuprofen
      showed 86.4% activity at the same oral dose. Four compounds, 4-(1H-indol-3-yl)-6
      (4-chlorophenyl)-1,2,3,4-tetrahydropyrimidin-2-one (8), 4-(1H-indol-3-yl)-6-(4
      methylphenyl)-1,2,3,4-tetrahydropyrimidin-2-one (10), 4-(1H-indol-3-yl)-6-(4
      chlorophenyl)-1,2,3,4-tetrahydropyrimidin-2-thione (14), 4-(1H-indol-3-yl)-6-(4
      methylphenyl)-1,2,3,4-tetrahydropyrimidin-2-thione (16), that showed significant
      anti-inflammatory activity were selected to study their ulcerogenic and lipid
      peroxidation activities. All tested compounds showed significant reduction in the
      ulcerogenic potential and lipid peroxidation compared to the standard drug
      ibuprofen.

PMID- 19103581
TI  - Effect of ampicillin and chloroquine on humoral immune response elicited by
      bovine albumin encapsulated in liposomes.
AB  - Immune suppression resulting from chemoprophylaxis and potential drug interaction
      were investigated in experimental animals pre-medicated with ampicillin and
      chloroquine followed by immunization with bovine serum albumin bearing liposomes
      prepared by the reverse phase evaporation method. The prepared liposomes were
      evaluated for particle size, entrapment efficiency and in vitro release. Humoral
      immune response was measured in terms of systemic IgG antibody titre by the ELISA
      method. The present study showed that 7:3 molar ratio of soya phosphatidylcholine
      and cholesterol produced liposomes of mean diameter of 235.4 +/- 10.3 nm and
      entrapment efficiency of 41.3 +/- 3.2%. Ampicillin significantly (p < 0.05)
      decreased the antibody titre whereas chloroquine did not reduce the antibody
      titre significantly. The study will help in programming a new drug management and
      in characterization of vaccine-drug interaction.

PMID- 19103582
TI  - Perspectives from nurse leaders and chief information officers on health
      information technology implementation.
AB  - To enhance the limited empirical evidence in the literature, the authors
      developed new knowledge and information on the basis of implementation
      experiences (e.g., strategic planning, goals, outcomes, barriers, mistakes) of
      hospital executives with actual health information technology (HIT). The authors
      asked why hospital leaders implement HIT and how they do so, and then applied the
      answers to the theoretical framework of change management and leadership. The
      authors accomplished this through a qualitative research study design. Various
      employees from different levels of the organizational chart provide their
      perspectives, allowing the authors to examine internal trends related to HIT. The
      authors examined external trends through a comparative analysis of healthcare
      markets.

PMID- 19103583
TI  - Recruitment and retention of rural hospital administrators: a multifaceted
      approach.
AB  - A major challenge confronting healthcare delivery in the United States is the
      shortage of clinical professionals in rural areas. Although most of the research
      surrounding this problem has focused on physicians and nurses, other healthcare
      professionals have received much less attention. Although not a clinician or
      hands-on care provider, the hospital administrator is an integral component of
      rural healthcare delivery systems and is instrumental in the organization and
      delivery of services. This article examines some of the factors that impact the
      recruitment and retention process for rural hospital administrators. The authors
      suggest that recruitment and retention success can be best achieved by adopting a
      multifaceted approach that includes aspects of and considerations from 3 separate
      areas: personal, organizational, and community attributes. The authors provide
      recommendations and insights for rural hospital governing boards responsible for
      this process.

PMID- 19103584
TI  - Disparities in ADL and IADL disabilities among elders of Hispanic subgroups in
      the United States: results from the National Health Interview Survey 2001-2003.
AB  - The authors compared disability and functional limitation among elder Hispanic
      subgroups by using data from the 2001-2003 National Health Interview Survey
      (National Center for Health Statistics 2008a). The authors applied chi-square
      analysis for bivariate comparisons and used multiple logistic regression analyses
      for making comparisons, estimating odds ratios, and predicting disabilities.
      Results revealed a 21.4% rate of disability of any type in Hispanics. Puerto
      Ricans reported the highest rates of Activity of Daily Living (ADL) and
      Instrumental Activity of Daily Living (IADL) disabilities compared with other
      Hispanic subgroups (Mexicans, Cubans, Central and South Americans) and reported a
      higher rate than did Blacks. Cubans showed the lowest rate of IADL and any
      disability among Hispanics and a lower rate than did Whites. These findings
      highlight the high rates of intragroup variability among the U. S. Hispanic
      population. Among seniors, ADLs and IADLs were significant predictors of
      admission to nursing homes and use of paid home care, physician services, and
      palliative care.

PMID- 19103585
TI  - How to improve patient satisfaction when patients are already satisfied: a
      continuous process-improvement approach.
AB  - The authors present a methodology that measures improvement in customer
      satisfaction scores when those scores are already high and the production process
      is slow and thus does not generate a large amount of useful data in any given
      time period. The authors used these techniques with data from a midsized
      rehabilitation institute affiliated with a regional, nonprofit medical center.
      Thus, this article functions as a case study, the findings of which may be
      applicable to a large number of other healthcare providers that share both the
      mission and challenges faced by this facility. The methodology focused on 2
      factors: use of the unique characteristics of panel data to overcome the paucity
      of observations and a dynamic benchmarking approach to track process variability
      over time. By focusing on these factors, the authors identify some additional
      areas for process improvement despite the institute's past operational success.

PMID- 19103586
TI  - Abstract Book, XIII International Congress of Histochemistry and Cytochemistry
      ICHC2008, Imaging of Cell Dynamics, 23rd-27th August 2008, Medical University of
      Gdansk, Poland.

PMID- 19103587
TI  - Utilization of smoking cessation informational, interactive, and online community
      resources as predictors of abstinence: cohort study.
AB  - BACKGROUND: The association between greater utilization of Web-assisted tobacco
      interventions and increased abstinence rates is well recognized. However, there
      is little information on how utilization of specific website features influences
      quitting. OBJECTIVE: To determine the association between utilization of
      informational, interactive, and online community resources (eg. bulletin boards)
      and abstinence rates, with the broader objective to identify potential strategies
      for improving outcomes for Web-assisted tobacco interventions. METHODS: In Spring
      2004, a cohort of 607 quitplan.com users consented to participate in an
      evaluation of quitplan.com, a Minnesota branded version of QuitNet.com. We
      developed utilization measures for different site features: general information,
      interactive diagnostic tools and quit planning tools, online expert counseling,
      passive (ie, reading of bulletin boards) and active (ie, public posting) online
      community engagement, and one-to-one messaging with other virtual community
      members. Using bivariate, multivariate, and path analyses, we examined the
      relationship between utilization of specific site features and 30-day abstinence
      at 6 months. RESULTS: The most commonly used resources were the interactive quit
      planning tools (used by 77% of site users). Other informational resources (ie,
      quitting guides) were used more commonly (60% of users) than passive (38%) or
      active (24%) community features. Online community engagement through one-to-one
      messaging was low (11%) as was use of online counseling (5%). The 30-day
      abstinence rate among study participants at 6 months was 9.7% (95% Confidence
      Interval [CI] 7.3% - 12.1%). In the logistic regression model, neither the
      demographic data (eg, age, gender, education level, employment, or insurance
      status) nor the smoking-related data (eg, cigarettes per day, time to first
      morning cigarette, baseline readiness to quit) nor use of smoking cessation
      medications entered the model as significant predictors of abstinence.
      Individuals who used the interactive quit planning tools once, two to three
      times, or four or more times had an odds of abstinence of 0.65 (95% Confidence
      Interval [CI] 0.22 - 1.94), 1.87 (95% CI 0.77 - 4.56), and 2.35 (95% CI 1.0 -
      5.58), respectively. The use of one-to-one messages (reference = none vs 1 or
      more) entered the final model as potential predictor for abstinence, though the
      significance of this measure was marginal (OR = 1.91, 95% CI 0.92 - 3.97, P =
      .083). In the path analysis, an apparent association between active online
      community engagement and abstinence was accounted for in large part by increased
      use of interactive quitting tools and one-to-one messaging. CONCLUSIONS: Use of
      interactive quitting tools, and perhaps one-to-one messaging with other members
      of the online community, was associated with increased abstinence rates among
      quitplan.com users. Designs that facilitate use of these features should be
      considered.

PMID- 19103588
TI  - Phosphatidylinositol 3-kinase/AKT pathway regulates the endoplasmic reticulum to
      golgi traffic of ceramide in glioma cells: a link between lipid signaling
      pathways involved in the control of cell survival.
AB  - Different lines of evidence indicate that both aberrant activation of the
      phosphatidylinositol 3-OH kinase (PI3K)/Akt survival pathway and down-regulation
      of the death mediator ceramide play a critical role in the aggressive behavior,
      apoptosis resistance, and adverse clinical outcome of glioblastoma multiforme.
      Furthermore, the inhibition of the PI3K/Akt pathway and the up-regulation of
      ceramide have been found functional to the activity of many cytotoxic treatments
      against glioma cell lines and glioblastomas as well. A reciprocal control between
      PI3K/Akt and ceramide signaling in glioma cell survival/death is suggested by
      data demonstrating a protective role of PI3K/Akt on ceramide-induced cell death
      in glial cells. In this study we investigated the role of the PI3K/Akt pathway in
      the regulation of the ceramide metabolism in C6 glioma cells, a cell line in
      which the PI3K/Akt pathway is constitutively activated. Metabolic experiments
      performed with different radioactive metabolic precursors of sphingolipids and
      microscopy studies with fluorescent ceramides demonstrated that the chemical
      inhibition of PI3K and the transfection with a dominant negative Akt strongly
      inhibited ceramide utilization for the biosynthesis of complex sphingolipids by
      controlling the endoplasmic reticulum (ER) to Golgi vesicular transport of
      ceramide. These findings constitute the first evidence for a PI3K/Akt-dependent
      regulation of vesicle-mediated movements of ceramide in the ER-Golgi district.
      Moreover, the findings also suggest the activation of the PI3K/Akt pathway as
      crucial to coordinate the biosynthesis of membrane complex sphingolipids with
      cell proliferation and growth and/or to maintain low ceramide levels, especially
      as concerns those treatments that promote ceramide biosynthesis in the ER.

PMID- 19103589
TI  - Nucleophosmin is cleaved and inactivated by the cytotoxic granule protease
      granzyme M during natural killer cell-mediated killing.
AB  - Natural killer (NK) cells kill virus-infected or transformed target cells by
      delivering cytotoxic proteases called granzymes to the target cell cytosol. One
      of these proteases, granzyme M, is specifically expressed in NK cells and is
      thought to instigate a form of cell death distinct from that mediated by granzyme
      A or granzyme B. However, the mechanism of granzyme M-induced cell death is
      unclear at present, and few substrates for this granzyme have been reported to
      date. Here we show that the abundant nucleolar phosphoprotein, nucleophosmin
      (NPM), is cleaved and inactivated by granzyme M. NPM is essential for cell
      viability as RNA interference-mediated ablation of NPM expression in human cells
      resulted in spontaneous apoptosis. Significantly, overexpression of wild-type NPM
      rescued cells treated with NPM small interference RNA, whereas overexpression of
      the granzyme M-cleaved form of NPM did not. Because NPM is essential for cell
      viability, these data suggest that targeting of NPM by granzyme M may contribute
      to tumor cell eradication by abolishing NPM function.

PMID- 19103590
TI  - Differences in chain usage and cross-linking specificities of cartilage type V/XI
      collagen isoforms with age and tissue.
AB  - Collagen type V/XI is a minor but essential component of collagen fibrils in
      vertebrates. We here report on age- and tissue-related variations in isoform
      usage in cartilages. With maturation of articular cartilage, the alpha1(V) chain
      progressively replaced the alpha2(XI) chain. A mix of the molecular isoforms,
      alpha1(XI)alpha1(V)alpha3(XI) and alpha1(XI)alpha2(XI)alpha3(XI), best explained
      this finding. A prominence of alpha1(V) chains is therefore characteristic and a
      potential biomarker of mature mammalian articular cartilage. Analysis of cross
      linked peptides showed that the alpha1(V) chains were primarily cross-linked to
      alpha1(XI) chains in the tissue and hence an integral component of the V/XI
      polymer. From nucleus pulposus of the intervertebral disc (in which the bulk
      collagen monomer is type II as in articular cartilage), type V/XI collagen
      consisted of a mix of five genetically distinct chains, alpha1(XI), alpha2(XI),
      alpha3(XI), alpha1(V), and alpha2(V). These presumably were derived from several
      different molecular isoforms, including alpha1(XI)alpha2(XI)alpha3(XI),
      (alpha1(XI))(2)alpha2(V), and others. Meniscal fibrocartilage shows yet another
      V/XI phenotype. The findings support and extend the concept that the clade B
      subfamily of COL5 and COL11 gene products should be considered members of the
      same collagen subfamily, from which, in combination with clade A gene products
      (COL2A1 or COL5A2), a range of molecular isoforms has evolved into tissue
      dependent usage. We propose an evolving role for collagen V/XI isoforms as an
      adaptable polymeric template of fibril macro-architecture.

PMID- 19103591
TI  - Analyzing the interaction of RseA and RseB, the two negative regulators of the
      sigmaE envelope stress response, using a combined bioinformatic and experimental
      strategy.
AB  - The Escherichia coli envelope stress response is controlled by the alternative
      sigma factor, sigma(E), and is induced when unfolded outer membrane proteins
      accumulate in the periplasm. The response is initiated by sequential cleavage of
      the membrane-spanning antisigma factor, RseA. RseB is an important negative
      regulator of envelope stress response that exerts its negative effects onsigma(E)
      activity through its binding to RseA. In this study, we analyze the interaction
      between RseA and RseB. We found that tight binding of RseB to RseA required
      intact RseB. Using programs that performed global and local sequence alignment of
      RseB and RseA, we found regions of high similarity and performed alanine
      substitution mutagenesis to test the hypothesis that these regions were
      functionally important. This protocol is based on the hypothesis that
      functionally dependent regions of two proteins co-evolve and therefore are likely
      to be sequentially conserved. This procedure allowed us to identify both an N
      terminal and C-terminal region in RseB important for binding to RseA. We
      extensively analyzed the C-terminal region, which aligns with a region of RseA
      coincident with the major RseB binding determinant in RseA. Both allele-specific
      suppression analysis and cysteine-mediated disulfide bond formation indicated
      that this C-terminal region of similarity of RseA and RseB identifies a contact
      site between the two proteins. We suggest a similar protocol can be successfully
      applied to pairs of non-homologous but functionally linked proteins to find
      specific regions of the protein sequences that are important for establishing
      functional linkage.

PMID- 19103593
TI  - Time of day-dependent sorting of the vesicular glutamate transporter to the
      plasma membrane.
AB  - Neurotransmitters are concentrated into synaptic vesicles by VGLUT (vesicular
      glutamate transporter) or VGAT (vesicular GABA transporter). The number of VGLUTs
      per vesicle determines the amount of stored neurotransmitter, thereby influencing
      postsynaptic response. Recently, we described a strong diurnal cycling of the
      amount of VGLUT1 on synaptic vesicles prepared from whole mouse brain at
      different times of the day (Yelamanchili, S. V., Pendyala, G., Brunk, I., Darna,
      M., Albrecht, U., and Ahnert-Hilger, G. (2006) J. Biol. Chem. 281, 15671-15679).
      To analyze whether and how much VGLUT resides in cellular versus vesicular
      membranes, we developed a Pronase assay. We found that VGLUT and synaptotagmin
      are highly accessible to proteolytic cleavage in rat and mouse synaptosomal
      preparations, indicating considerable amounts of these vesicular proteins at the
      plasma membrane, whereas only minor amounts of synaptophysin and Rab3 are
      digested. Sucrose stimulation increases digestion of VGLUT, synaptotagmin, and
      synaptophysin due to membrane fusion that exposes the lumen-facing peptides to
      the extracellular space. Digestion of mouse synaptosomes prepared at different
      times of the day revealed a diurnal cycling of VGLUT to the plasma membrane. More
      VGLUT is digested at noon (Zeitgeber time 6) compared with the start of the light
      period (Zeitgeber time 0), whereas digestion of synaptophysin and synaptotagmin
      is independent of diurnal cycling. In contrast to VGLUT, the amount of VGAT
      appears not to vary diurnally but is decreased in membrane preparations from
      animals kept under constant darkness. We conclude that VGLUTs are sorted
      diurnally to the plasma membrane to modulate glutamate transmission during a
      day/night cycle, whereas VGAT expression is not oscillating but is increased in
      the presence of a light/dark cycle.

PMID- 19103592
TI  - Ribosomal S6 kinase 2 directly phosphorylates the 5-hydroxytryptamine 2A (5-HT2A)
      serotonin receptor, thereby modulating 5-HT2A signaling.
AB  - The 5-hydroxytryptamine 2A (5-HT(2A)) receptor is a member of the G protein
      coupled receptor superfamily (GPCR) and plays a key role in transducing a variety
      of cellular signals elicited by 5-hydroxytryptamine in both peripheral and
      central tissues. Despite its broad physiological importance, our current
      understanding of 5-HT(2A) receptor regulation is incomplete. We recently reported
      the novel finding that the multifunctional ERK effector ribosomal S6 kinase 2
      (RSK2) physically interacts with the 5-HT(2A) receptor third intracellular (i3)
      loop and modulates receptor signaling (Sheffler, D. J., Kroeze, W. K., Garcia, B.
      G., Deutch, A. Y., Hufeisen, S. J., Leahy, P., Bruning, J. C., and Roth, B. L.
      (2006) Proc. Natl. Acad. Sci. U. S. A. 103, 4717-4722). We report here that RSK2
      directly phosphorylates the 5-HT(2A) receptor i3 loop at the conserved residue
      Ser-314, thereby modulating 5-HT(2A) receptor signaling. Furthermore, these
      studies led to the discovery that RSK2 is required for epidermal growth factor
      mediated heterologous desensitization of the 5-HT(2A) receptor. We arrived at
      these conclusions via multiple lines of evidence, including in vitro kinase
      experiments, tandem mass spectrometry, and site-directed mutagenesis. Our
      findings were further validated using phospho-specific Western blot analysis,
      metabolic labeling studies, and whole-cell signaling experiments. These results
      support a novel regulatory mechanism in which a downstream effector of the
      ERK/MAPK pathway directly interacts with, phosphorylates, and modulates signaling
      of the 5-HT(2A) serotonin receptor. To our knowledge, these findings are the
      first to demonstrate that a downstream member of the ERK/MAPK cascade
      phosphorylates a GPCR as well as mediates cross-talk between a growth factor and
      a GPCR.

PMID- 19103594
TI  - GRP78, but Not Protein-disulfide Isomerase, Partially Reverses Hyperglycemia
      induced Inhibition of Insulin Synthesis and Secretion in Pancreatic {beta}-Cells.
AB  - Chronic hyperglycemia contributes to pancreatic beta-cell dysfunction during the
      development of type 2 diabetes. Treatment of pancreatic beta-cells with prolonged
      high glucose concentrations has been shown to reduce insulin promoter activity
      and insulin gene expression. Here, we examined the effect of high glucose on
      endoplasmic reticulum (ER) stress pathway activation and insulin production in
      INS-1 832/13 pancreatic beta-cells. Treatment of cells with 25 mm glucose for 24
      48 h decreased insulin mRNA and protein levels and reduced the proinsulin
      translation rate, which was accompanied by enhanced unfolded protein response
      pathway activation (XBP-1 mRNA splicing and increased phospho-eIF2alpha, CHOP,
      and active ATF6 levels). Overexpressing the ER chaperone GRP78 partially rescued
      high glucose-induced suppression of proinsulin levels and improved glucose
      stimulated insulin secretion with no effect on insulin 2 mRNA levels. Under these
      conditions, there was little effect of GRP78 overexpression on ER stress markers.
      Knockdown of GRP78 expression under basal glucose conditions reduced cellular
      insulin levels and glucose-stimulated insulin secretion. Thus, GRP78 is essential
      for insulin biosynthesis, and enhancing chaperone capacity can improve beta-cell
      function in the presence of prolonged hyperglycemia. In contrast, overexpression
      of the ER chaperone and oxidoreductase protein-disulfide isomerase (PDI) reduced
      glucose-stimulated insulin secretion and induced ER stress resulting from the
      accumulation of proinsulin in the ER. These results suggest a role for both GRP78
      and PDI in insulin biosynthesis, although an excess of PDI disrupts normal
      proinsulin processing.

PMID- 19103595
TI  - Aberrant receptor internalization and enhanced FRS2-dependent signaling
      contribute to the transforming activity of the fibroblast growth factor receptor
      2 IIIb C3 isoform.
AB  - Alternative splice variants of fibroblast growth factor receptor 2 (FGFR2) IIIb,
      designated C1, C2, and C3, possess progressive reduction in their cytoplasmic
      carboxyl termini (822, 788, and 769 residues, respectively), with preferential
      expression of the C2 and C3 isoforms in human cancers. We determined that the
      progressive deletion of carboxyl-terminal sequences correlated with increasing
      transforming potency. The highly transforming C3 variant lacks five tyrosine
      residues present in C1, and we determined that the loss of Tyr-770 alone enhanced
      FGFR2 IIIb C1 transforming activity. Because Tyr-770 may compose a putative YXXL
      sorting motif, we hypothesized that loss of Tyr-770 in the 770YXXL motif may
      cause disruption of FGFR2 IIIb C1 internalization and enhance transforming
      activity. Surprisingly, we found that mutation of Leu-773 but not Tyr-770
      impaired receptor internalization and increased receptor stability and
      activation. Interestingly, concurrent mutations of Tyr-770 and Leu-773 caused 2
      fold higher transforming activity than caused by the Y770F or L773A single
      mutations, suggesting loss of Tyr and Leu residues of the 770YXXL773 motif
      enhances FGFR2 IIIb transforming activity by distinct mechanisms. We also
      determined that loss of Tyr-770 caused persistent activation of FRS2 by enhancing
      FRS2 binding to FGFR2 IIIb. Furthermore, we found that FRS2 binding to FGFR2 IIIb
      is required for increased FRS2 tyrosine phosphorylation and enhanced transforming
      activity by Y770F mutation. Our data support a dual mechanism where deletion of
      the 770YXXL773 motif promotes FGFR2 IIIb C3 transforming activity by causing
      aberrant receptor recycling and stability and persistent FRS2-dependent
      signaling.

PMID- 19103596
TI  - Putative re-entrant loop 1 of AE2 transmembrane domain has a major role in acute
      regulation of anion exchange by pH.
AB  - Normal pH sensitivity of the SLC4A2/AE2 anion exchanger requires transmembrane
      domain (TMD) amino acid (aa) residues not conserved in the homologous but
      relatively pH-insensitive SLC4A1/AE1 polypeptide. We tested the hypothesis that
      the nonconserved aa cluster 1075DKPK1078 within the first putative re-entrant
      loop (RL1) of AE2 TMD contributes to pH sensor function by studying anion
      exchange function of AE2 mutants in which these and other RL1 aa were
      systematically substituted with corresponding RL1 aa from AE1. Regulation of Cl
      /Cl- and Cl-/HCO(-)3 exchange by intracellular pH (pHi) or extracellular pH (pHo)
      was measured as 4,4'-di-isothiocyanatostilbene-2,2' disulfonic acid-sensitive
      36Cl- efflux from Xenopus oocytes. AE2 RL1 mutants 1075AAAQ1078 and 1075AAAQN1079
      showed reduced pHi sensitivity and pHo sensitivity was acid-shifted by
      approximately 1 pH unit. Individual mutants D1075A and P1077A exhibited
      moderately altered pH sensitivity, whereas a range of substitutions at conserved
      AE2 Ile-1079 substantially altered sensitivity to pHo and/or pHi. Substitution of
      the complete AE1 RL1 with AE2 RL1 failed to confer AE2-like pH sensitivity onto
      AE1. Replacement, however, of AE1 RL1 763SGPGAAAQ770 with AE2 1071VAPGDKPK1078
      restored pHi sensitivity to the chimera AE2(1-920)/AE1(613-929) without affecting
      its low sensitivity to pHo. The results show that acute regulation of AE2 by pH
      requires RL1 of the TMD. We propose that critical segments of RL1 constitute part
      of an AE2 pH sensor that, together with residues within the N-terminal half of
      the TMD, constrain the AE2 polypeptide in a conformation required for regulation
      of anion exchange by pHi.

PMID- 19103597
TI  - Caveolin-1 expression is required for the development of pulmonary emphysema
      through activation of the ATM-p53-p21 pathway.
AB  - Free radicals play a role in aging and age-related human diseases, including
      pulmonary emphysema. Cigarette smoke represents a source of oxidants and is
      considered an environmental hazard that causes pulmonary emphysema. Here, we show
      that caveolin-1 activates ataxia telangiectasia-mutated (ATM) after oxidative
      stress by sequestering the ATM inhibitor, the catalytic subunit of protein
      phosphatase 2A, into caveolar membranes. We demonstrate that cigarette smoke
      extracts promote stress-induced premature senescence in wild type but not
      caveolin-1 null lung fibroblasts and that caveolin-1 expression is required for
      activation of the ATM-p53-p21(Waf1)(/)(Cip1) pathway following stimulation with
      cigarette smoke extracts in vitro. In vivo studies show that caveolin-1
      expression is necessary for cigarette smoking-induced senescence of lung
      fibroblasts and pulmonary emphysema. These findings bring new insights into the
      molecular mechanism underlying free radical activation of the ATM-p53 pathway and
      indicate that caveolin-1 is a novel therapeutic target for the treatment and/or
      prevention of pulmonary emphysema.

PMID- 19103598
TI  - Structure-based ligand design and the promise held for antiprotozoan drug
      discovery.
AB  - The development of the pharmaceutical industry, driven by progress in chemistry,
      biology, and technology, ranks as one of the most successful of human endeavors.
      However, serious health problems persist, among which are diseases caused by
      protozoan parasites, largely ignored in modern times. Advances in genomic
      sciences, molecular and structural biology, and computational and medicinal
      chemistry now set the scene for a renewed assault on such infections. A structure
      centric approach to support discovery of antiparasitic compounds promises much.
      Current strategies and benefits of a structure-based approach to support early
      stage drug discovery will be described.

PMID- 19103599
TI  - Ligand reduces galectin-1 sensitivity to oxidative inactivation by enhancing
      dimer formation.
AB  - Galectin-1 (Gal-1) regulates leukocyte turnover by inducing the cell surface
      exposure of phosphatidylserine (PS), a ligand that targets cells for phagocytic
      removal, in the absence of apoptosis. Gal-1 monomer-dimer equilibrium appears to
      modulate Gal-1-induced PS exposure, although the mechanism underlying this
      regulation remains unclear. Here we show that monomer-dimer equilibrium regulates
      Gal-1 sensitivity to oxidation. A mutant form of Gal-1, containing C2S and V5D
      mutations (mGal-1), exhibits impaired dimerization and fails to induce cell
      surface PS exposure while retaining the ability to recognize carbohydrates and
      signal Ca(2+) flux in leukocytes. mGal-1 also displayed enhanced sensitivity to
      oxidation, whereas ligand, which partially protected Gal-1 from oxidation,
      enhanced Gal-1 dimerization. Continual incubation of leukocytes with Gal-1
      resulted in gradual oxidative inactivation with concomitant loss of cell surface
      PS, whereas rapid oxidation prevented mGal-1 from inducing PS exposure.
      Stabilization of Gal-1 or mGal-1 with iodoacetamide fully protected Gal-1 and
      mGal-1 from oxidation. Alkylation-induced stabilization allowed Gal-1 to signal
      sustained PS exposure in leukocytes and mGal-1 to signal both Ca(2+) flux and PS
      exposure. Taken together, these results demonstrate that monomer-dimer
      equilibrium regulates Gal-1 sensitivity to oxidative inactivation and provides a
      mechanism whereby ligand partially protects Gal-1 from oxidation.

PMID- 19103601
TI  - Structural Basis for the Immunogenic Properties of the Meningococcal Vaccine
      Candidate LP2086.
AB  - LP2086 is a family of outer membrane lipoproteins from Neisseria meningitidis,
      which elicits bactericidal antibodies and are currently undergoing human clinical
      trials in a bivalent formulation where each antigen represents one of the two
      known LP2086 subfamilies. Here we report the NMR structure of the recombinant
      LP2086 variant B01, a representative of the LP2086 subfamily B. The structure
      reveals a novel fold composed of two domains: a "taco-shaped" N-terminal beta
      sheet and a C-terminal beta-barrel connected by a linker. The structure in
      micellar solution is consistent with a model of LP2086 anchored to the outer
      membrane bilayer through its lipidated N terminus. A long flexible chain connects
      the folded part of the protein to the lipid anchor and acts as spacer, making
      both domains accessible to the host immune system. Antibodies broadly reactive
      against members from both subfamilies have been mapped to the N terminus. A
      surface of subfamily-defining residues was identified on one face of the protein,
      offering an explanation for the induction of subfamily-specific bactericidal
      antibodies.

PMID- 19103600
TI  - A PGC-1alpha-O-GlcNAc transferase complex regulates FoxO transcription factor
      activity in response to glucose.
AB  - Metabolic and stress response gene regulation is crucial for the survival of an
      organism to a changing environment. Three key molecules that sense nutrients and
      broadly affect gene expression are the FoxO transcription factors, the
      transcriptional co-activator PGC-1alpha, and the dynamic post-translational
      modification, O-linked beta-N-acetylglucosamine (O-GlcNAc). Here we identify
      novel post-translational modifications of PGC-1alpha, including O-GlcNAc, and
      describe a novel mechanism for how PGC-1alpha co-activates transcription by
      FoxOs. In liver, in cultured cells, and in vitro with recombinant proteins, PGC
      1alpha binds to O-GlcNAc transferase and targets the enzyme to FoxOs, resulting
      in their increased GlcNAcylation and increased transcriptional activity.
      Furthermore, glucose-enhanced activation of FoxO1 occurs via this PGC-1alpha-O
      GlcNAc transferase-mediated GlcNAcylation. Therefore, one mechanism by which PGC
      1alpha can serve as a co-activator of transcription is by targeting the O-GlcNAc
      transferase to increase GlcNAcylation of specific transcription factors important
      to nutrient/stress sensing and energy metabolism.

PMID- 19103602
TI  - Structure and functional analysis of RifR, the type II thioesterase from the
      rifamycin biosynthetic pathway.
AB  - Two thioesterases are commonly found in natural product biosynthetic clusters, a
      type I thioesterase that is responsible for removing the final product from the
      biosynthetic complex and a type II thioesterase that is believed to perform
      housekeeping functions such as removing aberrant units from carrier domains. We
      present the crystal structure and the kinetic analysis of RifR, a type II
      thioesterase from the hybrid nonribosomal peptide synthetases/polyketide synthase
      rifamycin biosynthetic cluster of Amycolatopsis mediterranei. Steady-state
      kinetics show that RifR has a preference for the hydrolysis of acyl units from
      the phosphopantetheinyl arm of the acyl carrier domain over the hydrolysis of
      acyl units from the phosphopantetheinyl arm of acyl-CoAs as well as a modest
      preference for the decarboxylated substrate mimics acetyl-CoA and propionyl-CoA
      over malonyl-CoA and methylmalonyl-CoA. Multiple RifR conformations and
      structural similarities to other thioesterases suggest that movement of a helical
      lid controls access of substrates to the active site of RifR.

PMID- 19103605
TI  - Molecular determinants differentiating photocurrent properties of two
      channelrhodopsins from chlamydomonas.
AB  - A light signal is converted into an electrical one in a single molecule named
      channelrhodopsin, one of the archaea-type rhodopsins in unicellular green algae.
      Although highly homologous, two molecules of this family, channelrhodopsin-1
      (ChR1) and -2 (ChR2), are distinct in photocurrent properties such as the
      wavelength sensitivity, desensitization, and turning-on and -off kinetics.
      However, the structures regulating these properties have not been completely
      identified. Photocurrents were analyzed for several chimera molecules made by
      replacing N-terminal segments of ChR2 with the homologous counterparts of ChR1.
      We found that the wavelength sensitivity of the photocurrent was red-shifted with
      negligible desensitization and slowed turning-on and -off kinetics when
      replacement was made with the segment containing the fifth transmembrane helix of
      ChR1. Therefore, this segment is involved in the determination of photocurrent
      properties, the wavelength sensitivity, and the kinetics characterizing ChR1 and
      ChR2. Eight amino acid residues differentiating this segment were exchanged one
      by-one, and the photocurrent properties of each targeted mutant ChR2 were further
      analyzed. Among them, position Tyr(226)(ChR1)/Asn(187)(ChR2) is one of the
      molecular determinants involved in the wavelength sensitivity, desensitization,
      and turning-on and -off kinetics. It is suggested that these amino acid residues
      directly or indirectly interact with the chromophore as well as with the protein
      structure determining the photocurrent kinetics. Some of the chimera
      channelrhodopsins are suggested to have several advantages over the wild-type
      ChR2 in the introduction of light-induced membrane depolarization for the purpose
      of artificial stimulation of neurons in vivo and visual prosthesis for
      photoreceptor degeneration.

PMID- 19103603
TI  - Night/day changes in pineal expression of >600 genes: central role of
      adrenergic/cAMP signaling.
AB  - The pineal gland plays an essential role in vertebrate chronobiology by
      converting time into a hormonal signal, melatonin, which is always elevated at
      night. Here we have analyzed the rodent pineal transcriptome using Affymetrix
      GeneChip(R) technology to obtain a more complete description of pineal cell
      biology. The effort revealed that 604 genes (1,268 probe sets) with Entrez Gene
      identifiers are differentially expressed greater than 2-fold between midnight and
      mid-day (false discovery rate <0.20). Expression is greater at night in
      approximately 70%. These findings were supported by the results of radiochemical
      in situ hybridization histology and quantitative real time-PCR studies. We also
      found that the regulatory mechanism controlling the night/day changes in the
      expression of most genes involves norepinephrine-cyclic AMP signaling. Comparison
      of the pineal gene expression profile with that in other tissues identified 334
      genes (496 probe sets) that are expressed greater than 8-fold higher in the
      pineal gland relative to other tissues. Of these genes, 17% are expressed at
      similar levels in the retina, consistent with a common evolutionary origin of
      these tissues. Functional categorization of the highly expressed and/or night/day
      differentially expressed genes identified clusters that are markers of
      specialized functions, including the immune/inflammation response, melatonin
      synthesis, photodetection, thyroid hormone signaling, and diverse aspects of
      cellular signaling and cell biology. These studies produce a paradigm shift in
      our understanding of the 24-h dynamics of the pineal gland from one focused on
      melatonin synthesis to one including many cellular processes.

PMID- 19103604
TI  - hNOA1 interacts with complex I and DAP3 and regulates mitochondrial respiration
      and apoptosis.
AB  - Mitochondria are dynamic organelles that play key roles in metabolism, energy
      production, and apoptosis. Coordination of these processes is essential to
      maintain normal cellular functions. Here we characterized hNOA1, the human
      homologue of AtNOA1 (Arabidopsis thaliana nitric oxide-associated protein 1), a
      large mitochondrial GTPase. By immunofluorescence, immunoelectron microscopy, and
      mitochondrial subfractionation, endogenous hNOA1 is localized within mitochondria
      where it is peripherally associated with the inner mitochondrial membrane facing
      the mitochondrial matrix. Overexpression and knockdown of hNOA1 led to changes in
      mitochondrial shape implying effects on mitochondrial dynamics. To identify the
      interaction partners of hNOA1 and to further understand its cellular functions,
      we performed immunoprecipitation-mass spectrometry analysis of endogenous hNOA1
      from enriched mitochondrial fractions and found that hNOA1 interacts with both
      Complex I of the electron transport chain and DAP3 (death-associated protein 3),
      a positive regulator of apoptosis. Knockdown of hNOA1 reduces mitochondrial O(2)
      consumption approximately 20% in a Complex I-dependent manner, supporting a
      functional link between hNOA1 and Complex I. Moreover, knockdown of hNOA1 renders
      cells more resistant to apoptotic stimuli such as gamma-interferon and
      staurosporine, supporting a role for hNOA1 in regulating apoptosis. Thus, based
      on its interactions with both Complex I and DAP3, hNOA1 may play a role in
      mitochondrial respiration and apoptosis.

PMID- 19103606
TI  - Rho-kinase contributes to sustained RhoA activation through phosphorylation of
      p190A RhoGAP.
AB  - RhoA is transiently activated by specific extracellular signals such as
      endothelin-1 (ET-1) in vascular smooth muscle cells. RhoGAP negatively regulates
      RhoA activity: thus, RhoA becomes the GDP-bound inactive form afterward.
      Sustained activation of RhoA is induced with high doses of the extracellular
      signals and is implicated in certain diseases such as vasospasms. However, it
      remains largely unknown how prolonged activation of RhoA is induced. Here we show
      that Rho-kinase, an effector of RhoA, phosphorylated p190A RhoGAP at Ser(1150)
      and attenuated p190A RhoGAP activity in COS7 cells. Binding of Rnd to p190A
      RhoGAP is thought to enhance its activation. Phosphorylation of p190A RhoGAP by
      Rho-kinase impaired Rnd binding. Stimulation of vascular smooth muscle cells with
      a high dose of ET-1 provoked sustained RhoA activation and p190A RhoGAP
      phosphorylation, both of which were prohibited by a Rho-kinase inhibitor. The
      phosphomimic mutation of p190A RhoGAP weakened Rnd binding and RhoGAP activities.
      Taken together, these results suggest that ET-1 induces Rho-kinase activation and
      subsequent phosphorylation of p190A RhoGAP, leading to prolonged RhoA activation.

PMID- 19103607
TI  - Egr-1 negatively regulates calsequestrin expression and calcium dynamics in
      ventricular cells.
AB  - AIMS: The transcription factor early growth response-1 (Egr-1) is increased in
      models of cardiac pathology; however, it is unclear how Egr-1 impacts the heart.
      We sought to identify how Egr-1 regulates expression of proteins involved in
      cardiomyocyte calcium homeostasis. METHODS: Protein expression was measured by
      immunoblotting in control cardiac differentiated H9c2 cells or in H9c2 cells
      overexpressing wild-type Egr-1 (Egr-1) or an Egr-1 (I293F) mutant.
      Microspectrofluorimetry of fura-2-loaded cells was used to study calcium
      dynamics. Chromatin immunoprecipitation with anti-Egr-1 antibody was used to
      identify Egr-1-associated DNA. RESULTS: Calsequestrin (CSQ) expression was
      reduced in Egr-1- and profoundly reduced in I293F-expressing cells. Calreticulin,
      triadin, sarcoendoplasmic reticulum ATPase 2a, phospholamban, and phosphoserine
      16-phospholamban expression was unaffected. Calcium release from CSQ-dependent
      ryanodine-sensitive stores was reduced in Egr-1 and absent in I293F-expressing
      cells. In contrast, calcium release from calreticulin-dependent inositol 1,4,5
      trisphosphate stores was unaffected. In vivo and in vitro chromatin
      immunoprecipitation demonstrated Egr-1 binding to the CSQ2 promoter. The Egr-1
      binding region contains overlapping Egr-1, SP1, and nuclear factor of activated T
      cells (NFAT) sites and a CpG island. Reciprocal immunoprecipitation coupled to
      immunoblots indicated Egr-1:NFAT3 binding was present in all cells lines.
      Treatment with cyclosporin A, inhibition of DNA methylation using 5
      azadeoxycytidine, or inhibition of protein acetylation using sodium butyrate
      reduced CSQ expression. CONCLUSION: Our data suggest that Egr-1:DNA binding at
      the promoter, DNA methylation, and protein acetylation are important in CSQ
      repression. Moreover, we demonstrate that a reduction in CSQ protein is
      associated with abnormal calcium dynamics. We conclude that Egr-1 acts as a
      transcriptional repressor at the CSQ promoter, resulting in downregulation of
      CSQ, the major calcium storage protein that links excitation-contraction coupling
      in the cardiac sarcoendoplasmic reticulum.

PMID- 19103608
TI  - The role of poverty rate and racial distribution in the geographic clustering of
      breast cancer survival among older women: a geographic and multilevel analysis.
AB  - The authors examined disparities in survival among women aged 66 years or older
      in association with census-tract-level poverty rate, racial distribution, and
      individual-level factors, including patient-, treatment-, and tumor-related
      factors, utilization of medical care, and mammography use. They used linked data
      from the 1992-1999 Surveillance, Epidemiology, and End Results (SEER) programs,
      1991-1999 Medicare claims, and the 1990 US Census. A geographic information
      system and advanced statistics identified areas of increased or reduced breast
      cancer survival and possible reasons for geographic variation in survival in 2 of
      the 5 SEER areas studied. In the Detroit, Michigan, area, one geographic cluster
      of shorter-than-expected breast cancer survival was identified (hazard ratio (HR)
      = 1.60). An additional area where survival was longer than expected approached
      statistical significance (HR = 0.4; P = 0.056). In the Atlanta, Georgia, area,
      one cluster of shorter- (HR = 1.81) and one cluster of longer-than-expected (HR =
      0.72) breast cancer survival were identified. Stage at diagnosis and census-tract
      poverty (and patient's race in Atlanta) explained the geographic variation in
      breast cancer survival. No geographic clusters were identified in the 3 other
      SEER programs. Interventions to reduce late-stage breast cancer, focusing on
      areas of high poverty and targeting African Americans, may reduce disparities in
      breast cancer survival in the Detroit and Atlanta areas.

PMID- 19103609
TI  - Screening methods for delirium: early diagnosis by means of objective
      quantification of motor activity patterns using wrist-actigraphy.
AB  - Delirium after cardiac surgery is a risk factor for adverse outcome and even
      death. Disturbance of motor activity is a core feature of delirium, but
      hypoactive delirium often remains unrecognized. We explored wrist-actigraphy as a
      tool to objectively quantify postoperative recovery of 24-h rest-activity
      patterns to improve the early recognition of delirium after surgery. Motor
      activity was recorded by wrist-actigraphy after cardiac surgery in 88 patients
      over 65 years of age. Patients were assessed daily by using the CAM-ICU. Our
      final analyses were based on 32 non-delirious patients and 38 patients who were
      delirious on the first day after surgery. The delirious patients showed lower
      mean activity levels during the first postoperative night (P<0.05), reduced
      restlessness during the first day (P<0.05), and a lower mean activity of the 5 h
      with lowest activity within the first 24 h (P=0.01), as compared to the non
      delirious patients. Already at a very early stage after cardiac surgery, a
      difference in motor activity was observed between patients with and without a
      delirium. As an unobtrusive method, actigraphy has the potential to be a
      screening method that may lead to early diagnosis and treatment of delirium.

PMID- 19103610
TI  - Collagenous gastritis.
AB  - A 25-year-old patient presented with epigastric pain, which on gastric biopsy
      revealed the characteristic appearance of collagenous gastritis. There was a
      thick prominent subepithelial band that was confirmed to be collagen with a
      Masson's trichrome stain. There was associated Helicobacter pylori gastritis but
      no evidence of a lymphocytic gastritis. The patient did not have watery diarrhea.
      Collagenous gastritis can occur in young patients, be restricted to the stomach,
      and can be associated with celiac disease.

PMID- 19103611
TI  - Microarray-based gene expression profiling as a clinical tool for breast cancer
      management: are we there yet?
AB  - Breast cancer is a heterogeneous disease, encompassing several histological types
      and clinical behaviors. Current histopathological classification systems are
      based on descriptive entities with prognostic significance. Few prognostic and
      predictive markers beyond those offered by histopathological analysis are
      available. High-throughput molecular technologies are reshaping our understanding
      of breast cancer, of which microarray-based gene expression has received most
      attention. This method has been used to derive a molecular taxonomy for breast
      cancer, which has provided interesting insights into the biology of the disease.
      Class prediction studies have generated a multitude of prognostic/predictive
      signatures, which herald the promise for an improvement in treatment decision
      making. However, most of the signatures developed to date seem to have
      discriminatory power almost restricted to estrogen receptor-positive disease.
      This review addresses the contribution of gene expression profiling to our
      understanding of breast cancer and its clinical management.

PMID- 19103612
TI  - Review of a large clinical series: association of cumulative fluid balance on
      outcome in acute lung injury: a retrospective review of the ARDSnet tidal volume
      study cohort.
AB  - OBJECTIVE: To evaluate the independent influence of fluid balance on outcomes for
      patients with acute lung injury. DESIGN: Secondary analysis of a prospective
      cohort study conducted between March 1996 and March 1999. SETTING: The study
      involved 10 academic clinical centers (with 24 hospitals and 75 Intensive Care
      Units). PATIENTS: All patients for whom fluid balance data existed (844) from the
      902 patients enrolled in the National Heart Lung Blood Institute's ARDS Network
      ventilator-tidal volume trial. INTERVENTIONS: The study had no interventions.
      MEASUREMENTS/RESULTS: On the first day of study enrollment, 683 patients were, on
      average, more than 3.5 L in positive fluid balance compared to 161 patients in
      negative fluid balance (P < .001). Cumulative negative fluid balance on day 4 of
      the study was associated with an independently lower hospital mortality (OR,
      0.50; 95% CI, 0.28-0.89; P < .001) more ventilator and intensive care unit-free
      days. CONCLUSIONS: Negative cumulative fluid balance at day 4 of acute lung
      injury is associated with significantly lower mortality, independent of other
      measures of severity of illness.

PMID- 19103613
TI  - Variations in understanding the drug-prescribing process: a qualitative study
      among Swedish GPs.
AB  - BACKGROUND: A majority of doctor-patient meetings result in the patient getting a
      prescription. This underlines the need for a high-quality prescription process.
      While studies have been made on single therapeutic drug groups, a complete study
      of the physicians' general thought process that comprises the prescription of all
      drugs still remains to be made. OBJECTIVE: To identify variations in ways of
      understanding drug prescribing among GPs. METHODS: A descriptive qualitative
      study was conducted with 20 Swedish physicians. Informants were recruited
      purposively and their understandings about prescribing were studied in semi
      structured interviews. Data were analysed using a phenomenographic approach.
      RESULTS: Five categories were identified as follows: (A) GP prescribed safe,
      reliable and well-documented drugs for obvious complaints; (B) GP sought to
      convince the patient of the most effective drug treatment; (C) GP chose the best
      drug treatment taking into consideration the patient's entire life situation; (D)
      GP used clinical judgement and close follow-up to minimize unnecessary drug
      prescribing and (E) GP prescribed drugs which are cheap for society and
      environmentally friendly. The categories are interrelated, but have different
      foci: the biomedical, the patient and the society. Each GP had more than one view
      but none included all five. The findings also indicate that complexity increases
      when a drug is prescribed for primary or secondary prevention. CONCLUSIONS: GPs
      understand prescribing differently despite similar external circumstances. The
      most significant factor to influence prescribing behaviour was the physician's
      patient relation approach. GPs may need to reflect on difficulties they face
      while prescribing to enhance their understandings.

PMID- 19103614
TI  - Efficacy of immunising pigs against porcine circovirus type 2 at three or six
      weeks of age.
AB  - The efficacy of a porcine circovirus type 2 (pcv-2) vaccine was tested in pigs
      vaccinated at three or six weeks of age. A total of 1106 weaned pigs were
      randomly allocated to one of three treatment groups: vaccinated at three weeks of
      age, vaccinated at six weeks of age, or not vaccinated. Each pig was weighed at
      three, 10 and 22 weeks of age, and 48 pigs selected at random from each treatment
      group were serially blood sampled at three, six, 10, 14, 18 and 22 weeks of age.
      The mean weight of the vaccinated pigs was 6.1 kg heavier at 22 weeks than the
      unvaccinated pigs. The combined mortality and cull rates of the unvaccinated pigs
      during the growing/finishing period was 14.1 per cent compared with 3.6 per cent
      and 3.1 per cent for the pigs vaccinated at three weeks and six weeks,
      respectively. The vaccinated pigs also had a significantly higher mean daily
      weight gain and a smaller load of humoral pcv-2 than the unvaccinated pigs.

PMID- 19103615
TI  - Screening of bovine coagulase-negative staphylococci from milk for superantigen
      encoding genes.
AB  - A collection of 102 coagulase-negative staphylococci (CNS), isolated from cases
      of subclinical and clinical bovine mastitis and belonging to 10 different
      species, were screened by PCR for the presence of genes encoding enterotoxins and
      enterotoxin-like toxins (sea, seb, sec, sed, see, seg, seh, sei, sej, selk, sell,
      selm, seln, selo, selp, selq and selu), toxic shock syndrome toxin-1 (tst), and
      exfoliative toxins A and B (eta and etb). No toxin gene sequences were amplified
      from any of the isolates, indicating that superantigens encoded by genes
      detectable by the PCR tests used were not involved in the development of
      subclinical and clinical mastitis in cattle infected with the CNS isolates
      tested.

PMID- 19103616
TI  - Treatment of idiopathic chylothorax in 14 dogs by ligation of the thoracic duct
      and partial pericardiectomy.
AB  - The outcome and complications associated with thoracic duct ligation combined
      with partial pericardiectomy in 14 dogs with idiopathic chylothorax were
      investigated retrospectively. Nine of the dogs were treated in the uk and five in
      Italy. All of them were reassessed clinically four weeks after surgery and the
      respiratory function and any pleural fluid accumulation were evaluated; they were
      followed up by telephone contact for at least six months. Eleven of the dogs were
      clinically normal and had no radiographic signs of pleural effusion when
      reassessed after four weeks. Two showed radiographic signs of a minor
      accumulation of pleural fluid but were clinically normal; when reassessed after
      three months they showed similar radiographic signs and clinical findings; but
      after four months there was no evidence of pleural effusion. One dog had a major
      complication that required a second surgical intervention.

PMID- 19103617
TI  - Isolation of Porphyromonas levii from vaginal samples from cows in herds negative
      for bovine necrotic vulvovaginitis.

PMID- 19103618
TI  - Incomplete placentation after twin reduction in a mare.

PMID- 19103619
TI  - Multiple hepatic vascular cysts in a young ragdoll cat.

PMID- 19103620
TI  - Career paths of alumni of the Cornell Leadership Program for veterinary students.
AB  - The Cornell Leadership Program at Cornell University, usa, aims to assist
      talented veterinary students to embark on careers in research, academia,
      government agencies or industry. Over 400 students have participated since the
      Program began in 1990 and their subsequent careers have been followed. In this
      study, five sources of data were analysed: application documents of the
      participants; audio recordings of interviews with each participant from 2000 to
      2007; annual tracking records of alumni after graduating with a veterinary
      degree; spontaneous comments from alumni about how the Program influenced their
      career plans; and a list of published scientific papers by alumni. Analysis
      revealed that about 50 per cent of veterinary graduates were establishing
      themselves in careers envisaged by the Program, although many of them experienced
      conflicts between a vocational commitment to clinical practice and a desire to
      solve problems through research. Many alumni asserted that the Program had
      influenced their career plans, but they had difficulty in accepting that rigorous
      scientific training was more important in acquiring research skills than working
      directly on a veterinary research problem. One career of great appeal to alumni
      was that of veterinary translational science, in which disease mechanisms are
      defined through fundamental research. It is concluded from the data that there
      are three challenging concepts for recently qualified veterinarians aiming to
      advance the knowledge of animal disease: research careers are satisfying and
      rewarding for veterinarians; a deep understanding of the chosen field of research
      is needed; and a high standard of scientific training is required to become an
      effective veterinary scientist.

PMID- 19103621
TI  - Is the veterinary profession divided and in decline?

PMID- 19103622
TI  - Mentoring for farmers in Wales.

PMID- 19103624
TI  - Changes to BSE surveillance and the end of the OCDS.

PMID- 19103625
TI  - Tiamulin activity against Brachyspira hyodysenteriae.

PMID- 19103626
TI  - Celebrating 20th century veterinary lives.

PMID- 19103627
TI  - Management of low back pain.

PMID- 19103628
TI  - Blood pressure self monitoring: questions and answers from a national conference.

PMID- 19103629
TI  - South African hospitals overflow as Zimbabweans seek treatment for cholera.

PMID- 19103631
TI  - German paediatricians want law changed to make it easier to report child abuse.

PMID- 19103632
TI  - Clinical efficacy and side effects of antimalarials in systemic lupus
      erythematosus: a systematic review.
AB  - BACKGROUND: Antimalarial drugs (AMs), chloroquine (CQ) and hydroxychloroquine
      (HCQ), are frequently withdrawn in patients with lupus with either severe or
      remitting disease. However, additional effects beyond immunomodulation have been
      recently described. The aim of the present work was to analyse all the published
      evidence of the beneficial and adverse effects of AM therapy in systemic lupus
      erythematosus (SLE). METHODS: A systematic review of the English literature
      between 1982 and 2007 was conducted using the MEDLINE and EMBASE databases.
      Randomised controlled trials (RCTs) and observational studies were selected. Case
      reports were excluded except for toxicity reports. The GRADE system was used to
      analyse the quality of the evidence. RESULTS: A total of 95 articles were
      included in the systematic review. High levels of evidence were found that AMs
      prevent lupus flares and increase long-term survival of patients with SLE;
      moderate evidence of protection against irreversible organ damage, thrombosis and
      bone mass loss. Toxicity related to AMs is infrequent, mild and usually
      reversible, with HCQ having a safer profile. In pregnant women, high levels of
      evidence were found that AMs, particularly HCQ, decrease lupus activity without
      harming the baby. By contrast, evidence supporting an effect on severe lupus
      activity, lipid levels and subclinical atherosclerosis was weak. Individual
      papers suggest effects in preventing the evolution from SLE-like to full-blown
      SLE, influencing vitamin D levels and protecting patients with lupus against
      cancer. CONCLUSIONS: Given the broad spectrum of beneficial effects and the
      safety profile, HCQ should be given to most patients with SLE during the whole
      course of the disease, irrespective of its severity, and be continued during
      pregnancy.

PMID- 19103633
TI  - Gene expression in human chondrocytes in late osteoarthritis is changed in both
      fibrillated and intact cartilage without evidence of generalised chondrocyte
      hypertrophy.
AB  - OBJECTIVES: To investigate changes in gene expression in fibrillated and intact
      human osteoarthritis (OA) cartilage for evidence of an altered chondrocyte
      phenotype and hypertrophy. METHODS: Paired osteochondral samples were taken from
      a high-load site and a low-load site from 25 OA joints and were compared with
      eight similar paired samples from age-matched controls. Gene expression of key
      matrix and regulatory genes was analysed by quantitative real-time reverse
      transcription-polymerase chain reaction on total RNA extracted from the
      cartilage. RESULTS: There was a major change in chondrocyte gene expression in OA
      cartilage. SOX9 (38-fold) and aggrecan (4-fold) gene expression were both lower
      in OA (p<0.001), and collagen I (17-fold) and II (2.5-fold) gene expression were
      each increased in a subset of OA samples. The major changes in gene expression
      were similar at the fibrillated high-loaded site and the intact low-loaded site.
      There was no evidence of a generalised change in OA to proliferative or
      hypertrophic phenotype as seen in the growth plate, as genes associated with
      either stage of differentiation were unchanged (PTHrPR), or significantly
      downregulated (collagen X (14-fold, p<0.002), VEGF (23-fold, p<0.02), BCL-2 (5.6
      fold, p<0.001), matrilin-1 (6.5-fold, p<0.001)). In contrast MMP-13 was
      significantly upregulated in the OA cartilage samples (5.3-fold, p<0.003).
      CONCLUSIONS: The expression of key chondrocyte genes, including aggrecan and
      SOX9, was decreased in OA cartilage and the changes were similar in both
      fibrillated high-loaded and intact low-loaded cartilage on the same joint.
      However, there was no significant upregulation of type X collagen, and other
      genes associated with chondrocyte further differentiation and hypertrophy.

PMID- 19103634
TI  - Change in regional cartilage morphology and joint space width in osteoarthritis
      participants versus healthy controls: a multicentre study using 3.0 Tesla MRI and
      Lyon-Schuss radiography.
AB  - OBJECTIVE: Cartilage morphology displays sensitivity to change in osteoarthritis
      (OA) with quantitative MRI (qMRI). However, (sub)regional cartilage thickness
      change at 3.0 Tesla (T) has not been directly compared with radiographic
      progression of joint space narrowing in OA participants and non-arthritic
      controls. METHODS: A total of 145 women were imaged at 7 clinical centres: 86
      were non-obese and asymptomatic without radiographic OA and 55 were obese with
      symptomatic and radiographic OA (27 Kellgren-Lawrence grade (KLG)2 and 28 KLG3).
      Lyon-Schuss (LS) and fixed flexion (FF) radiographs were obtained at baseline, 12
      and 24 months, and coronal spoiled gradient echo MRI sequences at 3.0 T at
      baseline, 6, 12 and 24 months. (Sub)regional, femorotibial cartilage thickness
      and minimum joint space width (mJSW) in the medial femorotibial compartment were
      measured and the standardised response means (SRMs) determined. RESULTS: At 6
      months, qMRI demonstrated a -3.7% "annualised" change in cartilage thickness (SRM
      -0.33) in the central medial femorotibial compartment (cMFTC) of KLG3 subjects,
      but no change in KLG2 subjects. The SRM for mJSW in 12-month LS/FF radiographs of
      KLG3 participants was -0.68/-0.13 and at 24 months was -0.62/-0.20. The SRM for
      cMFTC changes measured with qMRI was -0.32 (12 months; -2.0%) and -0.48 (24
      months; -2.2%), respectively. CONCLUSIONS: qMRI and LS radiography detected
      significant change in KLG3 participants at high risk of progression, but not in
      KLG2 participants, and only small changes in controls. At 12 and 24 months, LS
      displayed greater, and FF less, sensitivity to change in KLG3 participants than
      qMRI.

PMID- 19103635
TI  - From gene expression to serum proteins: biomarker discovery in ankylosing
      spondylitis.
AB  - OBJECTIVES: Studying post-infliximab gene expression changes could provide
      insights into the pathogenesis of ankylosing spondylitis (AS). METHODS: Gene
      expression changes were screened by microarray on peripheral blood RNA of 16 AS
      patients at baseline and 2 weeks post-infliximab, and selected results were
      confirmed by quantitative real-time (qRT)-PCR. Corresponding serum-soluble LIGHT
      (sLIGHT) was estimated by ELISA and the fold change in sLIGHT was correlated to
      the fold change in erythrocyte sedimentation rate (ESR), C-reactive protein (CRP)
      and the Bath AS disease activity index. RESULTS: Post-infliximab, 69% of the
      patients (11/16) achieved an ASAS20 response. Six candidate genes were
      differentially expressed by microarray; four of which were validated by qRT-PCR.
      sLIGHT showed the most significant difference. There was good correlation of
      baseline sLIGHT with CRP (R = 0.60; p = 0.01) and ESR (R = 0.51; p = 0.04). The
      fold change in sLIGHT correlated with change in both CRP (R = 0.71, p = 0.002)
      and ESR (R = 0.77, p<0.001). CONCLUSION: LIGHT is significantly downregulated by
      infliximab. sLIGHT correlated well with changes in inflammatory markers.

PMID- 19103636
TI  - Rituximab in diffuse cutaneous systemic sclerosis: an open-label clinical and
      histopathological study.
AB  - OBJECTIVES: The safety and potential efficacy of rituximab was examined in
      diffuse cutaneous systemic sclerosis (dc-SSc). METHODS: A 24 week open-label
      study in which eight patients with dc-SSc received an infusion of 1000 mg
      rituximab administered at baseline and day 15, together with 100 mg
      methylprednisolone at each infusion. Assessment included CD19+ peripheral blood
      lymphocyte number, skin sclerosis score, indices of internal organ functioning,
      the health assessment questionnaire disability index, the 36-item Short Form
      health survey and histopathological evaluation of the skin. RESULTS: Ritixumab
      induced effective B-cell depletion in all patients (<5 CD19+ cells/microl blood).
      There was a significant change in skin score at week 24 (p<0.001). Also,
      significant improvements were measured in the dermal hyalinised collagen content
      (p = 0.014) and dermal myofibroblast numbers (p = 0.011). Two serious adverse
      events occurred, which were thought to be unrelated to the rituximab treatment.
      CONCLUSIONS: Rituximab appears to be well tolerated and may have potential
      efficacy for skin disease in dc-SSc.

PMID- 19103637
TI  - The metabolic syndrome is amplified in hypothyroid rheumatoid arthritis patients:
      a cross-sectional study.
AB  - OBJECTIVES: Rheumatoid arthritis (RA) patients are at increased risk of
      cardiovascular disease (CVD), which is even more pronounced in hypothyroid RA
      patients. An unfavourable cardiovascular risk profile conferred by a higher
      prevalence of the metabolic syndrome (MetS) and a higher Framingham risk score
      might explain this amplified cardiovascular morbidity. This study compared first,
      MetS (features) and second, the Framingham 10-year CVD risk in RA patients with
      hypothyroidism compared with euthyroid RA patients. METHODS: RA patients
      participating in the CARRE investigation were divided into two groups:
      hypothyroid and euthyroid RA patients. MetS according to the National Cholesterol
      Education Program Third Adult Treatment Panel criteria and the Framingham risk
      score was compared between hypothyroid and non-hypothyroid CVD event-free RA
      patients. RESULTS: In total, 257 RA patients were included: 236 with RA (91.8%)
      and 21 with hypothyroid RA (8.2%), respectively. The prevalence of the MetS was
      significantly higher in hypothyroid RA patients (43%) compared with RA patients
      (20%). Moreover, female hypothyroid RA patients had a higher Framingham risk
      score compared with euthyroid RA patients. With RA patients as the reference
      category, the age and gender-adjusted prevalence odds ratio for the MetS was 3.5
      (95% CI 1.3 to 9.1) in hypothyroid RA. CONCLUSIONS: Hypothyroid RA patients,
      particularly female patients, have a more unfavourable cardiovascular risk
      profile, reflected by an increased prevalence of the MetS and higher Framingham
      score, than euthyroid RA patients, suggesting a greater need for cardiovascular
      risk management in these patients to prevent future CVD events.

PMID- 19103638
TI  - A signature of evolutionary constraint on a subset of ectopically expressed
      olfactory receptor genes.
AB  - Olfactory receptor (OR) genes constitute the basis for the sense of smell. It has
      long been observed that a subset of mammalian OR genes are expressed in
      nonolfactory tissues, in addition to their expression in the olfactory
      epithelium. However, it is unknown whether OR genes have alternative functions in
      the nonolfactory tissues. Using a dedicated microarray, we surveyed OR gene
      expression in olfactory epithelium as well as a number of nonolfactory tissues,
      in human and chimpanzee. Our observations suggest that ectopically expressed OR
      orthologous genes are expressed in the same nonolfactory tissues in human and
      chimpanzee more often than expected by chance alone. Moreover, we found that the
      subset of orthologous OR genes with conserved ectopic expression evolve under
      stronger evolutionary constraint than OR genes expressed exclusively in the
      olfactory epithelium. Thus, although we cannot provide direct functional data,
      our observations are consistent with the notion that a subset of ectopically
      expressed OR genes have additional functions in nonolfactory tissues.

PMID- 19103639
TI  - The relationship between local clean indoor air policies and smoking behaviours
      in Minnesota youth.
AB  - BACKGROUND: While clean indoor air (CIA) policies are intended to reduce exposure
      to second-hand smoke in the workplace, restrictions in public workplaces have the
      potential to discourage youth smoking. There is growing evidence from cross
      sectional and ecological studies, but limited evidence from longitudinal studies
      that this is so. OBJECTIVE: To evaluate the association between local CIA
      policies and smoking behaviours among Minnesota youth over time. DESIGN, SETTING
      AND SUBJECTS: A cohort of 4233 Minnesota youths, ages 11 to 16 at baseline, was
      interviewed via telephone for 6 years (2000-2006). Individual, family and
      community level variables were collected from participants every 6 months. A
      generalised estimating equation (GEE) logistic regression was used to assess the
      relationship between CIA policies and past-month smoking in youth over time. The
      analysis was controlled for potential confounders at individual and community
      levels. RESULTS: There was not significant association between CIA policies and
      youth smoking behaviours in the multivariate analyses. At the individual level,
      parental smoking significantly increased the odds of smoking nearly 40% and close
      friend smoking increased the odds of past-month smoking by nearly 100% for each
      close friend. Banning smoking in the home was significantly associated with a 12%
      reduction in the odds of past-month smoking. CONCLUSION: After accounting for
      other community and individual level factors known to be associated with youth
      smoking, there was no significant association between CIA policies and past-month
      smoking for youth over time.

PMID- 19103640
TI  - Formative design and evaluation of patient-delivered partner therapy
      informational materials and packaging.
AB  - OBJECTIVE: To develop and evaluate instructional and packaging materials for
      patient-delivered partner therapy (PDPT). METHODS: 64 patients participated from
      an urban US sexually transmitted infection (STI) clinic. The research comprised
      three phases: individual interviews to elicit attitudes and beliefs regarding
      PDPT and to assess the understanding of key STI-related concepts and terminology;
      the development and rapid validation of prototype instructional and packaging
      materials for PDPT and interviews to assess the effectiveness, acceptability and
      usability of the prototype materials. Thematic qualitative data analysis was used
      to examine interview responses. RESULTS: Participants were willing to deliver and
      receive PDPT and several potentially important related beliefs were identified.
      Participants indicated substantial unfamiliarity with words associated with STI
      treatment and some variability in definitions of sex partners. PDPT informational
      materials differentially affected participant willingness to receive (positively)
      and deliver (negatively) PDPT, positively influenced self-efficacy and
      understanding and were perceived as easy to use. DISCUSSION: PDPT creates complex
      challenges for education, motivation and communication. Issues such as
      appropriate vocabulary and interpersonal trust may be amplified when
      responsibility for a medical procedure-dispensation of treatment-is shifted to
      patients. STI PDPT implementation can be augmented with effective, high-quality
      informational and packaging materials; however, several challenges exist.

PMID- 19103641
TI  - Effectiveness of an opting-out strategy for HIV testing: evaluation of 4 years of
      standard HIV testing in a STI clinic.
AB  - OBJECTIVES: A high proportion of individuals infected with HIV are unaware of the
      infection. They miss the opportunity for timely treatment. Our sexually
      transmitted infection (STI) clinic (South Limburg, The Netherlands) recognised
      the need to increase test rates and from 2004 routinely includes a HIV test,
      unless the client refuses, in each consultation. We evaluated the effectiveness
      of this opting-out approach for HIV testing. METHODS: We used anonymised data
      from our STI clinic from 2003-2007 to assess trends in HIV testing and (reasons
      for) test refusal using multivariate analyses and interview. Laboratory registry
      data from the area that is served by the clinic were evaluated as well. RESULTS:
      In South Limburg the number of HIV tests increased, which was mostly due to
      increasing STI clinic requests and antenatal screening. Of STI clinic attendees,
      84% (1616/1920) were tested in 2003 and this proportion increased to 96%
      (3699/3836) in 2007. However, 88% (n = 57/65) of men who have sex with men and
      44% (191/424) of heterosexuals who refused HIV testing after 2004 were linked to
      higher STI/HIV risk. Our clinic now uses these findings to develop more effective
      and tailored HIV/STI counselling in order to further optimise HIV testing
      practice. CONCLUSIONS: Standard testing on HIV in a STI clinic is feasible and
      effective in increasing awareness of one's HIV status. It should be an essential
      part of STI screening in STI clinics and should be considered in other healthcare
      settings for specific risk groups.

PMID- 19103642
TI  - Opting out increases HIV testing in a large sexually transmitted infections
      outpatient clinic.
AB  - OBJECTIVES: In January 2007, opt-out HIV testing replaced provider-initiated
      testing at the sexually transmitted infections (STI) outpatient clinic in
      Amsterdam, The Netherlands. The effect of the opt-out strategy on the uptake of
      HIV testing was studied and factors associated with refusal of HIV testing were
      identified. STUDY DESIGN: Data routinely collected at the STI clinic were
      analysed separately for men who have sex with men (MSM) and heterosexuals.
      Logistic regression analysis was used to identify factors associated with opting
      out. RESULTS: In 2007, 12% of MSM and 4% of heterosexuals with (presumed)
      negative or unknown HIV serostatus declined HIV testing. Refusals gradually
      decreased to 7% and 2% by the year end. In 2006, before the introduction of opt
      out, 38% of MSM and 27% of heterosexuals declined testing. The proportion of HIV
      positive results remained stable among MSM, 3.4% in 2007 versus 3.7% in 2006, and
      among heterosexuals, 0.2% in 2007 versus 0.3% in 2006. In both groups factors
      associated with opting out were: age >or=30 years, no previous HIV test, the
      presence of STI-related complaints and no risky anal/vaginal intercourse. Among
      heterosexuals, men and non-Dutch visitors refused more often; among MSM, those
      warned of STI exposure by sexual partners and those diagnosed with gonorrhoea or
      syphilis refused more often. CONCLUSIONS: An opt-out strategy increased the
      uptake of HIV testing. A sharp increase in testing preceeded a more gradual
      increase, suggesting time must pass to optimise the new strategy. A small group
      of visitors, especially MSM, still opt out. Counselling will focus on barriers
      such as fear and low risk perception among high-risk visitors considering opting
      out.

PMID- 19103644
TI  - Protein kinase C-dependent alpha-secretory processing of the amyloid precursor
      protein is mediated by phosphorylation of myosin II-B.
AB  - A substantial body of evidence indicates that protein kinase C (PKC) is involved
      in the alpha-secretory processing of the amyloid precursor protein (APP), an
      event that reduces the formation of the pathogenic amyloid-beta peptide.
      Recently, we have shown that trafficking and processing of APP are both impaired
      by knockdown of myosin II-B, one of the major neuronal motor proteins. Here, we
      provide evidence that the alpha-secretory processing of APP is mediated by PKC
      dependent phosphorylation of myosin II-B. This signaling pathway provides an
      important link between APP and the neuronal cytoskeleton and might be crucial for
      the understanding of the biological and pathological roles of APP.

PMID- 19103643
TI  - Selective induction of integrin beta1 by hypoxia-inducible factor: implications
      for wound healing.
AB  - Because of localized vascular damage and increased tissue oxygen demand, wound
      healing occurs in a relatively hypoxic microenvironment. These features are
      particularly relevant to wound healing and fibrosis in chronic inflammatory
      conditions, such as Crohn's disease and ulcerative colitis. In these studies, we
      sought to identify the contribution of hypoxia to mechanisms of wound repair in a
      model of the intestinal submucosa. Initial studies revealed that hypoxia promotes
      wound healing, as modeled by an increase in intestinal fibroblast-mediated
      collagen gel contraction. Guided by results from transcriptional profiling, we
      identified the selective induction of fibroblast integrin beta1 (ITGB1) by
      hypoxia. Further analysis revealed that hypoxia, as well as pharmacological
      activators of hypoxia-inducible factor (HIF), induce fibroblast beta1 integrin
      mRNA, protein, and function by as much as 4-fold. Cloning and analysis of the
      beta1 integrin gene promoter revealed a 10 +/- 0.8-fold increase in promoter
      activity in response to hypoxia, and subsequent studies identified a functional
      DNA binding region for HIF in the ITGB1 gene promoter. Mutational analysis of the
      HIF binding site within the ITGB1 promoter resulted in a significant loss of
      ITGB1 hypoxia-inducibility. As proof of principle, studies in a murine model of
      colitis revealed a correlation between colitic disease severity and tissue ITGB1
      expression (R(2)=0.80). Taken together, these results demonstrate that hypoxia
      induces fibroblast ITGB1 expression and function by transcriptional mechanisms
      dependent on HIF.

PMID- 19103645
TI  - Molecular genetic analysis of a human insulin-like growth factor 1 promoter P1
      variation.
AB  - Insulin-like growth factor 1 (IGF1) exerts important endocrine and paracrine
      functions in the cardiovascular system. We identified the common variant -1411C>T
      in the IGF1 upstream promoter P1, located within several overlapping
      transcription factor binding sites. Using transient transfection assays, we
      identified this site as a functional enhancer. The T allele-carrying enhancer,
      compared with the C allelic portion, exerts significantly reduced or even
      abrogated activity, respectively, in SaOs-2 and HepG2 (all P<0.0001) as well as
      in differentiated THP-1 macrophages. Electrophoretic mobility shift assay and
      subsequent supershift experiments in HepG2 identified c-Jun as the binding
      partner exclusively to the T allele, whereas CCAAT/enhancer-binding protein delta
      and interferon consensus site-binding protein/interferon-regulating factor 8
      interacted only with the C allelic promoter portion. Furthermore, genotyping in a
      case-control study for essential hypertension (n=745 hypertensive patients; n=769
      normotensive control subjects) for this variant revealed an odds ratio for
      hypertension of 0.73 (95% confidence interval 0.58-0.91, P=0.006) associated with
      the T allele, and normotensive subjects carrying the protective T allele
      displayed a significant decrease in diastolic (P=0.036) and systolic (P=0.024)
      blood pressure levels. We here report detection of a functional enhancer module
      in the upstream IGF1 promoter region, which might play a key role in local IGF1
      bioavailability. Whether -1411C>T is also associated with other IGF1-related
      disease phenotypes should be evaluated further in population studies.

PMID- 19103646
TI  - Maternal nutrient restriction during pregnancy differentially alters the unfolded
      protein response in adipose and renal tissue of obese juvenile offspring.
AB  - Maternal diet during pregnancy can program an offspring's risk of disease in
      later life. Obesity adversely alters renal and adipose tissue function, resulting
      in chronic kidney disease and insulin resistance, respectively, the latter
      associated with dysregulation of the unfolded protein response (UPR). In view of
      the current obesity epidemic, we explored the combined effects of in utero early-
      to midgestational nutrient restriction and postnatal obesity on the UPR in ovine
      juvenile offspring. Nutrient restriction was coincident with fetal kidney
      development but prior to exponential adipose tissue deposition. Nutrient
      restricted (NR) and normal diet (control) offspring were exposed to an obesogenic
      environment throughout adolescence, resulting in similar degrees of juvenile
      obesity. NR offspring showed enhanced adipose tissue dysregulation characterized
      by activation of the UPR, perturbed insulin signaling, and marked inflammation,
      as demonstrated by increased abundance of crownlike structures and
      proinflammatory genes. Conversely, in renal tissue NR offspring had marked
      attenuation of cellular stress and inflammation evident as reduced activation of
      the UPR, down-regulation of proinflammatory genes, and less histological damage.
      In conclusion, obesity-related activation of the UPR can be determined by the in
      utero nutritional environment, demonstrating organ-specific effects dependent on
      the developmental phase targeted within the fetus.

PMID- 19103647
TI  - Two common single nucleotide polymorphisms in the gene encoding beta-carotene
      15,15'-monoxygenase alter beta-carotene metabolism in female volunteers.
AB  - The key enzyme responsible for beta-carotene conversion into retinal is beta
      carotene 15,15'-monoxygenase (BCMO1). Since it has been reported that the
      conversion of beta-carotene into vitamin A is highly variable in up to 45% of
      healthy individuals, we hypothesized that genetic polymorphisms in the BCMO1 gene
      could contribute to the occurrence of the poor converter phenotype. Here we
      describe the screening of the total open reading frame of the BCMO1 coding region
      that led to the identification of two common nonsynonymous single nucleotide
      polymorphisms (R267S: rs12934922; A379V: rs7501331) with variant allele
      frequencies of 42 and 24%, respectively. In vitro biochemical characterization of
      the recombinant 267S + 379V double mutant revealed a reduced catalytic activity
      of BCMO1 by 57% (P<0.001). Assessment of the responsiveness to a pharmacological
      dose of beta-carotene in female volunteers confirmed that carriers of both the
      379V and 267S + 379V variant alleles had a reduced ability to convert beta
      carotene, as indicated through reduced retinyl palmitate:beta-carotene ratios in
      the triglyceride-rich lipoprotein fraction [-32% (P=0.005) and -69% (P=0.001),
      respectively] and increased fasting beta-carotene concentrations [+160% (P=0.025)
      and +240% (P=0.041), respectively]. Our data show that there is genetic
      variability in beta-carotene metabolism and may provide an explanation for the
      molecular basis of the poor converter phenotype within the population.

PMID- 19103648
TI  - Differential contribution of the Na(+)-K(+)-2Cl(-) cotransporter NKCC1 to
      chloride handling in rat embryonic dorsal root ganglion neurons and motor
      neurons.
AB  - Plasma membrane chloride (Cl(-)) pathways play an important role in neuronal
      physiology. Here, we investigated the role of NKCC1 cotransporters (a secondary
      active Cl(-) uptake mechanism) in Cl(-) handling in cultured rat dorsal root
      ganglion neurons (DRGNs) and motor neurons (MNs) derived from fetal stage
      embryonic day 14. Gramicidin-perforated patch-clamp recordings revealed that
      DRGNs accumulate intracellular Cl(-) through a bumetanide- and Na(+)-sensitive
      mechanism, indicative of the functional expression of NKCC1. Western blotting
      confirmed the expression of NKCC1 in both DRGNs and MNs, but immunocytochemistry
      experiments showed a restricted expression in dendrites of MNs, which contrasts
      with a homogeneous expression in DRGNs. Both MNs and DRGNs could be readily
      loaded with or depleted of Cl(-) during GABA(A) receptor activation at
      depolarizing or hyperpolarizing membrane potentials. After loading, the rate of
      recovery to the resting Cl(-) concentration (i.e., [Cl(-)](i) decrease) was
      similar in both cell types and was unaffected by lowering the extracellular Na(+)
      concentration. In contrast, the recovery on depletion (i.e., [Cl(-)](i) increase)
      was significantly faster in DRGNs in control conditions but not in low
      extracellular Na(+). The experimental observations could be reproduced by a
      mathematical model for intracellular Cl(-) kinetics, in which DRGNs show higher
      NKCC1 activity and smaller Cl(-)-handling volume than MNs. On the basis of these
      results, we conclude that embryonic DRGNs show a higher somatic functional
      expression of NKCC1 than embryonic MNs. The high NKCC1 activity in DRGNs is
      important for maintaining high [Cl(-)](i), whereas lower NKCC1 activity in MNs
      allows large [Cl(-)](i) variations during neuronal activity.

PMID- 19103649
TI  - Calcineurin inhibition in splenocytes induced by pavlovian conditioning.
AB  - Pavlovian conditioning is one of the major neurobiological mechanisms of placebo
      effects, potentially influencing the course of specific diseases and the response
      to a pharmacological therapy, such as immunosuppression. In our study with
      behaviorally conditioned rats, a relevant taste (0.2% saccharin) preceded the
      application of the immunosuppressive drug cyclosporin A (CsA), a specific
      calcineurin (CaN) inhibitor. Our results demonstrate that through pavlovian
      conditioning the particular pharmacological properties of CsA can be transferred
      to a neutral taste, i.e., CaN activity was inhibited in splenocytes from
      conditioned rats after reexposure to the gustatory stimulus. Concomitant immune
      consequences were observed on ex vivo mitogenic challenge (anti-CD3).
      Particularly, Th1-cytokine, but not Th2-cytokine, production and cell
      proliferation were impeded. Appropriate pharmacological and behavioral controls
      certify that all these changes in T-lymphocyte reactivity are attributable to
      mere taste reexposure. Furthermore, the underlying sympathetic-lymphocyte
      interaction was revealed modeling the conditioned response in vitro. CaN activity
      in CD4(+) T lymphocytes is reduced by beta-adrenergic stimulation (terbutaline),
      with these effects antagonized by the beta-adrenoreceptor antagonist nadolol. In
      summary, CaN was identified as the intracellular target for inducing conditioned
      immunosuppression by CsA, contributing to our understanding of the intracellular
      mechanisms behind "learned placebo effects."

PMID- 19103651
TI  - Pitfalls of internal cardioverter defibrillator implantation: part II.

PMID- 19103650
TI  - Regulation of peroxisome proliferator-activated receptor-alpha by MDM2.
AB  - Peroxisome proliferator-activated receptor-alpha (PPARalpha) belongs to the
      nuclear receptor (NR) family of transcription factors and regulates lipid and
      glucose metabolism. Like other NRs, the regulation of gene expression by
      PPARalpha depends on cofactor recruitment to the transcription complex and
      multiple protein-protein interactions. In this study, Murine Double Minute 2
      (MDM2), an E3 ubiquitin ligase, is identified as a PPARalpha-interacting protein
      that regulates PPARalpha transcriptional activity. MDM2 modulated the
      transcriptional activity of PPARalpha and PPARbeta/delta, but not PPARgamma in
      reporter assays. Knockdown of MDM2 by small interfering RNA in rat hepatoma cells
      inhibited ligand-induced mRNA levels of several PPARalpha target genes involved
      in lipid metabolism. MDM2 associated with PPARalpha on target gene promoters, and
      this association increased in response to Wy14,643 treatment. MDM2 interacted
      with PPARalpha and this interaction occurred with the A/B domain of PPARalpha.
      Coexpression of MDM2 increased PPARalpha ubiquitination and the E3 ubiquitin
      ligase activity of MDM2 affected PPARalpha protein expression and transcriptional
      activity. MDM2 expression was decreased in response to clofibrate in wild-type
      (WT), but not in PPARalpha null mice, indicating a PPARalpha-dependent
      regulation. These studies identify a role for MDM2 in regulating PPARalpha
      mediated pathways of lipid metabolism.

PMID- 19103652
TI  - Pitfalls of internal cardioverter defibrillator implantation: part I.

PMID- 19103653
TI  - Interference of transcutaneous electrical nerve stimulation with permanent
      ventricular stimulation: a new clinical problem?
AB  - AIMS: To assess the compatibility of thoracic TENS and permanent PM treatment and
      to identify any signs of interference of TENS with the PM function. METHODS AND
      RESULTS: Twenty-seven patients treated with PM were tested. Transcutaneous
      electric nerve stimulation electrodes were placed above each mamilla, and the
      stimulation intensity was increased to the maximum level tolerated for 30 s or
      until electrocardiogram revealed signs of interference. Transcutaneous electric
      nerve stimulation of 2 and 80 Hz was tested with the PM ventricular sensing level
      set to the clinically chosen level as well as to maximal sensitivity.
      Interference was detected in 22 of 27 patients (81%). Low-frequency (2 Hz)
      stimulation was more associated with PM interference (52% at normal vs. 81% at
      maximal ventricular sensitivity) than high-frequency (80 Hz) stimulation (33% at
      normal vs. 63% at maximal ventricular sensitivity); although the differences were
      not statistically significant. CONCLUSION: Transcutaneous electric nerve
      stimulation frequently induces inhibition of the PM function already at the
      clinically set ventricular sensitivity. Therefore, individual testing is
      warranted before TENS treatment is considered in patients with a PM. A test
      protocol for TENS and PM interaction is proposed.

PMID- 19103654
TI  - Potential role of home monitoring to reduce inappropriate shocks in implantable
      cardioverter-defibrillator patients due to lead failure.
AB  - AIMS: Lead dysfunctions in implantable cardioverter-defibrillator (ICD) patients
      can lead to inappropriate shocks or even complete loss of function of the device.
      Home monitoring (HM) systems are capable of daily data transmissions regarding
      the device and the lead integrity as well as information concerning anti
      arrhythmic therapies. We therefore analysed the data from the Biotronik HM system
      whether it enables physicians to react quickly on serious ICD malfunctions and to
      avoid inappropriate shocks. METHODS AND RESULTS: Fifty-four patients who had to
      undergo resurgery due to malfunctions of the ICD lead were included. Eleven of
      them were on HM interrogating the device every night at 3 am. If any adverse
      event was detected, a fax alert was sent to the clinic and the patients were
      asked for in-hospital ICD interrogation. The rate of inappropriate shocks and
      symptomatic pacemaker inhibition due to oversensing was compared with the 43
      patients without remote surveillance. HM sent alert messages in 91% of all
      incidents. All lead failures became obvious because of oversensing of high
      frequency artefacts. Only in 18%, changes in the pacing impedance were noticed,
      in all cases preceded by oversensing. Eighty per cent of the patients were
      asymptomatic at the first onset of oversensing. Only one patient suffered an
      inappropriate shock as first manifestation of lead failure. Compared with the
      patients without HM, inappropriate shocks occurred in 27.3% in the HM group vs.
      46.5% (P = n.s.). This trend gains statistical significance, if the compound
      endpoint of symptomatic lead failure consisting of inappropriate shocks and
      symptomatic pacemaker inhibition due to oversensing is focused: 27.3% event in
      the HM group vs. 53.4% in the group without HM (P = 0.04). Event messages were
      despatched in a mean of 54 days after the last ICD interrogation and 56 days
      before next scheduled visit. Thus, 56 days of reaction time are gained to avoid
      adverse events. CONCLUSION: In 91% of all lead-related ICD complications, the
      diagnosis could be established correctly by an alert of the HM system. Mostly,
      the first incident sent was oversensing of artefacts, falsely detected as
      ventricular fibrillation-the VF zone. The automatic HM surveillance system
      enables physicians to detect severe lead problems early and to react quickly;
      thus, it might have a potential to avoid inappropriate shocks due to lead failure
      and T-wave oversensing.

PMID- 19103655
TI  - Early recovery of pulmonary vein conduction after cryoballoon ablation for
      paroxysmal atrial fibrillation: a prospective study.
AB  - AIMS: To assess the incidence of early pulmonary vein (PV) reconnection,
      characterize the anatomic features of the reconducting veins, and analyse the
      time course of their recovery in a series of consecutive patients with paroxysmal
      atrial fibrillation (AF) undergoing ablation with the Arctic Front Cryoballoon.
      METHODS AND RESULTS: We prospectively enrolled 26 patients (20 males; age 55.4 +/
      4.1) for circumferential PV cryoballoon isolation for highly symptomatic
      paroxysmal AF. Following isolation of all veins, we analysed PV potentials in
      each vein after 30 and 60 min with a circular mapping catheter. After successful
      electrical isolation of all 104 PV's, recurrence was observed only in three veins
      (2.8%) after 30 min. Two further cryoballoon applications in each of these veins
      lead to their isolation. These veins were still electrically disconnected at 60
      min. No PV reconnection was observed in any of the other 101 veins (97.1%) at 30
      and 60 min. CONCLUSION: Cryoballoon ablation of the PV's ostia is a very
      effective technique to achieve electrical isolation, with a very low rate of
      early reconnection.

PMID- 19103656
TI  - The advantages of being called NICE: a systematic review of journal article
      titles using the acronym for the National Institute for Health and Clinical
      Excellence.
AB  - OBJECTIVE: To describe the use of NICE, the acronym for the UK National Institute
      for Health and Clinical Excellence, as both an adjective and noun in peer
      reviewed journal article titles. DESIGN: Systematic review of titles retrieved by
      electronic database searches. DATA SOURCES: Ovid databases (MEDLINE, All EBM
      Reviews, EMBASE, ERIC, CINAHL and PsycINFO) covering the formation of NICE in
      1999 to February 2008. REVIEW METHODS: Independent review of eligible titles by
      both authors and resolution of disagreements based on consideration of full text
      articles. RESULTS: 2274 articles were retrieved that included reference to NICE
      in their titles. Of these, 167 (7.3%) used NICE as an adjective, most commonly in
      conjunction with the terms 'work', 'not so' (NICE), 'nasty', 'mess' and 'try'.
      CONCLUSIONS: The work of NICE has been widely referenced in peer-reviewed journal
      article titles, sometimes with apparent humorous intent when used as an
      adjective. Well-chosen names may increase the recognizability of public health
      organizations and help to communicate their roles.

PMID- 19103657
TI  - Perceived priorities for prevention: change between 1996 and 2006 in a general
      population survey.
AB  - BACKGROUND: We assessed change between 1996 and 2006 in the opinions of the
      general public on priorities for the prevention of health problems. METHODS:
      Postal questionnaire surveys in 1996 and 2006, in representative samples of the
      general population of Geneva, Switzerland. Participants indicated, for each of 13
      health problems, a priority rating for the spending of prevention resources.
      RESULTS: There were 742 participants in 1996 (response rate 75%) and 1487 in 2006
      (response rate 76%). According to participants, in 2006, resources should be
      spent, with priority, for: the prevention of sexual abuse of children (67%
      answered 'high priority'), illegal drugs (58%), AIDS (55%), tobacco smoking
      (45%), road traffic accidents (43%), alcoholism (42%), family violence (42%),
      suicide in young people (39%), mammography screening for breast cancer (37%),
      abuse of medications (27%), cannabis use (24%), poor diet (22%) and lack of
      physical activity (20%). Between 1996 and 2006, the largest change was observed
      for tobacco smoking (+18.6% answered 'high priority'), poor diet (+11.4%), lack
      of physical activity (+10.8%) and AIDS (-10.8%, P < 0.001 for all change scores).
      CONCLUSIONS: Smoking, poor diet and lack of physical activity were more likely to
      be perceived as priorities in 2006 than in 1996, whereas priority ratings
      decreased for AIDS. The prevention of sexual abuse of children was perceived as
      the highest priority by all respondent groups.

PMID- 19103658
TI  - Optimization of in vivo activity of a bifunctional homing endonuclease and
      maturase reverses evolutionary degradation.
AB  - The LAGLIDADG homing endonuclease (LHE) I-AniI has adopted an extremely efficient
      secondary RNA splicing activity that is beneficial to its host, balanced against
      inefficient DNA cleavage. A selection experiment identified point mutations in
      the enzyme that act synergistically to improve endonuclease activity. The amino
      acid substitutions increase target affinity, alter the thermal cleavage profile
      and significantly increase targeted recombination in transfected cells. The RNA
      splicing activity is not affected by these mutations. The improvement in DNA
      cleavage activity is largely focused on one of the enzyme's two active sites,
      corresponding to a rearrangement of a lysine residue hypothesized to act as a
      general base. Most of the constructs isolated in the screen contain one or more
      mutations that revert an amino-acid identity to a residue found in one or more
      close homologues of I-AniI. This implies that mutations that have previously
      reduced the endonuclease activity of I-AniI are identified and reversed,
      sometimes in combination with additional 'artificial' mutations, to optimize its
      in vivo activity.

PMID- 19103659
TI  - Model-based probe set optimization for high-performance microarrays.
AB  - A major challenge in microarray design is the selection of highly specific
      oligonucleotide probes for all targeted genes of interest, while maintaining
      thermodynamic uniformity at the hybridization temperature. We introduce a novel
      microarray design framework (Thermodynamic Model-based Oligo Design Optimizer,
      TherMODO) that for the first time incorporates a number of advanced modelling
      features: (i) A model of position-dependent labelling effects that is
      quantitatively derived from experiment. (ii) Multi-state thermodynamic
      hybridization models of probe binding behaviour, including potential cross
      hybridization reactions. (iii) A fast calibrated sequence-similarity-based
      heuristic for cross-hybridization prediction supporting large-scale designs. (iv)
      A novel compound score formulation for the integrated assessment of multiple
      probe design objectives. In contrast to a greedy search for probes meeting
      parameter thresholds, this approach permits an optimization at the probe set
      level and facilitates the selection of highly specific probe candidates while
      maintaining probe set uniformity. (v) Lastly, a flexible target grouping
      structure allows easy adaptation of the pipeline to a variety of microarray
      application scenarios. The algorithm and features are discussed and demonstrated
      on actual design runs. Source code is available on request.

PMID- 19103660
TI  - Quality assessment and data analysis for microRNA expression arrays.
AB  - MicroRNAs are small (approximately 22 nt) RNAs that regulate gene expression and
      play important roles in both normal and disease physiology. The use of
      microarrays for global characterization of microRNA expression is becoming
      increasingly popular and has the potential to be a widely used and valuable
      research tool. However, microarray profiling of microRNA expression raises a
      number of data analytic challenges that must be addressed in order to obtain
      reliable results. We introduce here a universal reference microRNA reagent set as
      well as a series of nonhuman spiked-in synthetic microRNA controls, and
      demonstrate their use for quality control and between-array normalization of
      microRNA expression data. We also introduce diagnostic plots designed to assess
      and compare various normalization methods. We anticipate that the reagents and
      analytic approach presented here will be useful for improving the reliability of
      microRNA microarray experiments.

PMID- 19103662
TI  - A novel chair-type G-quadruplex formed by a Bombyx mori telomeric sequence.
AB  - Recently, the human telomeric d[TAGGG(TTAGGG)(3)] sequence has been shown to form
      in K(+) solution an intramolecular (3+1) G-quadruplex structure, whose G-tetrad
      core contains three strands oriented in one direction and the fourth in the
      opposite direction. Here we present a study on the structure of the Bombyx mori
      telomeric d[TAGG(TTAGG)(3)] sequence, which differs from the human counterpart
      only by one G deletion in each repeat. We found that this sequence adopted
      multiple G-quadruplex structures in K(+) solution. We have favored a major G
      quadruplex form by a judicious U-for-T substitution in the sequence and
      determined the folding topology of this form. We showed by NMR that this was a
      new chair-type intramolecular G-quadruplex which involved a two-layer
      antiparallel G-tetrad core and three edgewise loops. Our result highlights the
      effect of G-tract length on the folding topology of G-quadruplexes, but also
      poses the question of whether a similar chair-type G-quadruplex fold exists in
      the human telomeric sequences.

PMID- 19103661
TI  - Characterization and expression profiles of miRNAs in rice seeds.
AB  - Small RNAs (sRNAs) are common and effective modulators of gene expression in
      eukaryotic organisms. To characterize the sRNAs expressed during rice seed
      development, massively parallel signature sequencing (MPSS) was performed,
      resulting in the obtainment of 797,399 22-nt sequence signatures, of which
      111,161 are distinct ones. Analysis on the distributions of sRNAs on chromosomes
      showed that most sRNAs originate from interspersed repeats that mainly consist of
      transposable elements, suggesting the major function of sRNAs in rice seeds is
      transposon silencing. Through integrative analysis, 26 novel miRNAs and 12 miRNA
      candidates were identified. Further analysis on the expression profiles of the
      known and novel miRNAs through hybridizing the generated chips revealed that most
      miRNAs were expressed preferentially in one or two rice tissues. Detailed
      comparison of the expression patterns of miRNAs and corresponding target genes
      revealed the negative correlation between them, while few of them are positively
      correlated. In addition, differential accumulations of miRNAs and corresponding
      miRNA*s suggest the functions of miRNA*s other than being passenger strands of
      mature miRNAs, and in regulating the miRNA functions.

PMID- 19103663
TI  - Phototoxic aptamers selectively enter and kill epithelial cancer cells.
AB  - The majority of cancers arise from malignant epithelial cells. We report the
      design of synthetic oligonucleotides (aptamers) that are only internalized by
      epithelial cancer cells and can be precisely activated by light to kill such
      cells. Specifically, phototoxic DNA aptamers were selected to bind to unique
      short O-glycan-peptide signatures on the surface of breast, colon, lung, ovarian
      and pancreatic cancer cells. These surface antigens are not present on normal
      epithelial cells but are internalized and routed through endosomal and Golgi
      compartments by cancer cells, thus providing a focused mechanism for their
      intracellular delivery. When modified at their 5' end with the photodynamic
      therapy agent chlorin e(6) and delivered to epithelial cancer cells, these
      aptamers exhibited a remarkable enhancement (>500-fold increase) in toxicity upon
      light activation, compared to the drug alone and were not cytotoxic towards cell
      types lacking such O-glycan-peptide markers. Our findings suggest that these
      synthetic oligonucleotide aptamers can serve as delivery vehicles in precisely
      routing cytotoxic cargoes to and into epithelial cancer cells.

PMID- 19103664
TI  - Structural analysis of DNA complexation with cationic lipids.
AB  - Complexes of cationic liposomes with DNA are promising tools to deliver genetic
      information into cells for gene therapy and vaccines. Electrostatic interaction
      is thought to be the major force in lipid-DNA interaction, while lipid-base
      binding and the stability of cationic lipid-DNA complexes have been the subject
      of more debate in recent years. The aim of this study was to examine the
      complexation of calf-thymus DNA with cholesterol (Chol), 1,2-dioleoyl-3
      trimethylammonium-propane (DOTAP), dioctadecyldimethylammoniumbromide (DDAB) and
      dioleoylphosphatidylethanolamine (DOPE), at physiological condition, using
      constant DNA concentration and various lipid contents. Fourier transform infrared
      (FTIR), UV-visible, circular dichroism spectroscopic methods and atomic force
      microscopy were used to analyse lipid-binding site, the binding constant and the
      effects of lipid interaction on DNA stability and conformation. Structural
      analysis showed a strong lipid-DNA interaction via major and minor grooves and
      the backbone phosphate group with overall binding constants of K(Chol) = 1.4 (+/
      0.5) x 10(4) M(-1), K(DDAB) = 2.4 (+/-0.80) x 10(4) M(-1), K(DOTAP) = 3.1 (+/
      0.90) x 10(4) M(-1) and K(DOPE) = 1.45 (+/- 0.60) x 10(4) M(-1). The order of
      stability of lipid-DNA complexation is DOTAP>DDAB>DOPE>Chol. Hydrophobic
      interactions between lipid aliphatic tails and DNA were observed. Chol and DOPE
      induced a partial B to A-DNA conformational transition, while a partial B to C
      DNA alteration occurred for DDAB and DOTAP at high lipid concentrations. DNA
      aggregation was observed at high lipid content.

PMID- 19103665
TI  - Kalign2: high-performance multiple alignment of protein and nucleotide sequences
      allowing external features.
AB  - In the growing field of genomics, multiple alignment programs are confronted with
      ever increasing amounts of data. To address this growing issue we have
      dramatically improved the running time and memory requirement of Kalign, while
      maintaining its high alignment accuracy. Kalign version 2 also supports
      nucleotide alignment, and a newly introduced extension allows for external
      sequence annotation to be included into the alignment procedure. We demonstrate
      that Kalign2 is exceptionally fast and memory-efficient, permitting accurate
      alignment of very large numbers of sequences. The accuracy of Kalign2 compares
      well to the best methods in the case of protein alignments while its accuracy on
      nucleotide alignments is generally superior. In addition, we demonstrate the
      potential of using known or predicted sequence annotation to improve the
      alignment accuracy. Kalign2 is freely available for download from the Kalign web
      site (http://msa.sbc.su.se/).

PMID- 19103666
TI  - Isolation and characterization of post-splicing lariat-intron complexes.
AB  - Pre-mRNA splicing occurs in a large complex spliceosome. The steps of both
      spliceosome assembly and splicing reaction have been extensively analyzed, and
      many of the factors involved have been identified. However, the post-splicing
      intron turnover process, especially in vertebrates, remains to be examined. In
      this paper, we developed a two-tag affinity purification method for purifying
      lariat intron RNA-protein complexes obtained from an in vitro splicing reaction.
      Glycerol gradient sedimentation analyses revealed that there are at least two
      forms of post-splicing intron complexes, which we named the 'Intron Large (IL)'
      and the 'Intron Small (IS)' complexes. The IL complex contains U2, U5 and U6
      snRNAs and other protein splicing factors, whereas the IS complex contains no
      such U snRNAs or proteins. We also showed that TFIP11, a human homolog of yeast
      Ntr1, is present in the IL complex and the TFIP11 mutant protein, which lacks the
      interaction domain with hPrp43 protein, caused accumulation of the IL complex and
      reduction of IS complex formation in vitro. Taken together, our results strongly
      suggest that TFIP11 in cooperation with hPrp43 mediates the transition from the
      IL complex to the IS complex, leading to efficient debranching and turnover of
      excised introns.

PMID- 19103667
TI  - Silencing-associated and meiosis-specific small RNA pathways in Paramecium
      tetraurelia.
AB  - Distinct small RNA pathways are involved in the two types of homology-dependent
      effects described in Paramecium tetraurelia, as shown by a functional analysis of
      Dicer and Dicer-like genes and by the sequencing of small RNAs. The siRNAs that
      mediate post-transcriptional gene silencing when cells are fed with double
      stranded RNA (dsRNA) were found to comprise two subclasses. DCR1-dependent
      cleavage of the inducing dsRNA generates approximately 23-nt primary siRNAs from
      both strands, while a different subclass of approximately 24-nt RNAs,
      characterized by a short untemplated poly-A tail, is strictly antisense to the
      targeted mRNA, suggestive of secondary siRNAs that depend on an RNA-dependent RNA
      polymerase. An entirely distinct pathway is responsible for homology-dependent
      regulation of developmental genome rearrangements after sexual reproduction.
      During early meiosis, the DCL2 and DCL3 genes are required for the production of
      a highly complex population of approximately 25-nt scnRNAs from all types of
      germline sequences, including both strands of exons, introns, intergenic regions,
      transposons and Internal Eliminated Sequences. A prominent 5'-UNG signature, and
      a minor fraction showing the complementary signature at positions 21-23, indicate
      that scnRNAs are cleaved from dsRNA precursors as duplexes with 2-nt 3' overhangs
      at both ends, followed by preferential stabilization of the 5'-UNG strand.

PMID- 19103669
TI  - Association study of the IL18RAP locus in three European populations with coeliac
      disease.
AB  - Coeliac disease is caused by dietary gluten, triggering a chronic inflammation of
      the small intestine in genetically predisposed individuals. Recently, a risk
      locus on chromosome 2q11-q12, harbouring interleukin 18 receptor accessory
      protein (IL18RAP) and three other genes, was suggested for coeliac disease. IL18
      has been shown to play an important role in T helper type 1 activity in coeliac
      disease, making this locus a highly interesting candidate. In this study, two
      previously indicated risk variants at the IL18RAP locus (rs13015714 and rs917997)
      were tested for genetic association in 1638 cases with coeliac disease and 1385
      control individuals from the Finnish, Hungarian and Italian populations. The
      protein expression level of IL18RAP was also compared between risk allele
      carriers and non-carriers by Western blotting. Furthermore, immunohistochemical
      analysis was performed to study IL18RAP protein expression in small intestinal
      biopsies of untreated and treated coeliac patients and controls. We confirmed
      genetic association and dose effects of variants at the 2q12.1 locus with coeliac
      disease in the Hungarian population. The GA haplotype of the markers rs13015714
      and rs917997 showed the strongest association (P = 0.0001, odds ratio = 1.475,
      95% confidence interval 1.21-1.80). Two putative isoforms of IL18RAP were
      detected and the ratios and total levels of these isoforms may contribute to the
      aetiology of coeliac disease. Our study supports IL18RAP as a novel predisposing
      gene for coeliac disease and highlights the need for further functional studies
      on this relatively unknown gene in coeliac disease pathogenesis.

PMID- 19103670
TI  - Editorial.

PMID- 19103668
TI  - Expansion of the human mu-opioid receptor gene architecture: novel functional
      variants.
AB  - The mu-opioid receptor (OPRM1) is the principal receptor target for both
      endogenous and exogenous opioid analgesics. There are substantial individual
      differences in human responses to painful stimuli and to opiate drugs that are
      attributed to genetic variations in OPRM1. In searching for new functional
      variants, we employed comparative genome analysis and obtained evidence for the
      existence of an expanded human OPRM1 gene locus with new promoters, alternative
      exons and regulatory elements. Examination of polymorphisms within the human
      OPRM1 gene locus identified strong association between single nucleotide
      polymorphism (SNP) rs563649 and individual variations in pain perception. SNP
      rs563649 is located within a structurally conserved internal ribosome entry site
      (IRES) in the 5'-UTR of a novel exon 13-containing OPRM1 isoforms (MOR-1K) and
      affects both mRNA levels and translation efficiency of these variants.
      Furthermore, rs563649 exhibits very strong linkage disequilibrium throughout the
      entire OPRM1 gene locus and thus affects the functional contribution of the
      corresponding haplotype that includes other functional OPRM1 SNPs. Our results
      provide evidence for an essential role for MOR-1K isoforms in nociceptive
      signaling and suggest that genetic variations in alternative OPRM1 isoforms may
      contribute to individual differences in opiate responses.

PMID- 19103671
TI  - A phase I trial of 5-fluorouracil with cisplatin and concurrent standard-dose
      radiotherapy in Japanese patients with stage II/III esophageal cancer.
AB  - OBJECTIVE: In Japan, 5-fluorouracil (5-FU) 400 mg/m(2) on Days 1-5, 8-12, 36-40
      and 43-46 with cisplatin (CDDP) 40 mg/m(2) on Days 1, 8, 36 and 43 plus
      concurrent radiotherapy with 2 weeks planned interruption (60 Gy) was standard
      for the patients with esophageal cancer. This Phase I trial was designed to
      determine the maximal tolerated dose (MTD) and dose-limiting toxicity (DLT) of 5
      FU on Days 1-4 and 29-32 with CDDP on Days 1 and 29 plus concurrent radiotherapy
      (50.4 Gy) among the Japanese. METHODS: Escalating doses of 5-FU and CDDP were
      administered with concurrent radiotherapy (50.4 Gy). Treatment was continued
      until DLT appeared. RESULTS: Twelve patients with previously untreated clinical
      Stage II/III squamous cell esophageal carcinoma were studied. One of six patients
      given Level 1 (5-FU 800 mg/m(2) on Days 1-4 and 29-32 with CDDP 75 mg/m(2) on
      Days 1 and 29) developed a DLT of incomplete protocol treatment due to Grade 3
      esophagitis. The MTD was not reached at Level 2 (5-FU 1000 mg/m(2) with CDDP 75
      mg/m(2)). The complete response rate was 67% at Level 1 and 100% at Level 2.
      CONCLUSIONS: Dose Level 2 with 50.4 Gy radiotherapy was recommended for Japanese
      patients.

PMID- 19103672
TI  - A case of locally advanced chondroblastoma in the proximal humerus.

PMID- 19103673
TI  - Comparison of time trends in stomach cancer incidence (1973-2002) in Asia, from
      Cancer Incidence in Five Continents, Vols IV-IX.

PMID- 19103674
TI  - Donor blood glucose 6-phosphate dehydrogenase deficiency reduces the efficacy of
      exchange transfusion in neonatal hyperbilirubinemia.
AB  - OBJECTIVES: Acute intravascular hemolysis after exchange transfusion with glucose
      6-phosphate dehydrogenase-deficient blood has been reported; however, it is not
      routine to screen donor blood for glucose 6-phosphate dehydrogenase deficiency
      while performing exchange transfusion. We hypothesized that exchange transfusion
      with glucose 6-phosphate dehydrogenase-deficient blood would lead to a less-than
      expected decrease in total serum bilirubin. The objective of this study was to
      evaluate the effect of exchange transfusion with glucose 6-phosphate
      dehydrogenase-deficient blood in neonates with idiopathic hyperbilirubinemia on
      postexchange total serum bilirubin levels, duration of phototherapy, and need for
      repeat exchange transfusions. METHODS: All neonates who were undergoing exchange
      transfusion for idiopathic hyperbilirubinemia were enrolled. A sample of donor
      blood was collected at the time of exchange transfusion for a glucose 6-phosphate
      dehydrogenase assay. The standard criteria for starting and stopping phototherapy
      and exchange transfusion were applied. RESULTS: During the 1-year study period,
      21 infants underwent exchange with glucose 6-phosphate dehydrogenase-deficient
      blood, and 114 neonates with similar baseline characteristics underwent exchange
      transfusion with glucose 6-phosphate dehydrogenase-normal blood. From 6 to 60
      hours after exchange transfusion, there was a significantly lesser drop in total
      serum bilirubin in the recipients of glucose 6-phosphate dehydrogenase-deficient
      donor blood compared with recipients of glucose 6-phosphate dehydrogenase-normal
      blood. The mean duration of phototherapy in the postexchange period and number of
      infants who underwent repeat exchange transfusions were significantly higher in
      recipients of glucose 6-phosphate dehydrogenase-deficient donor blood in
      comparison with control subjects. Concurrently, there was a significantly higher
      drop in hematocrit and rise in plasma hemoglobin in the glucose 6-phosphate
      dehydrogenase-deficient donor group. CONCLUSIONS: Exchange transfusion with
      glucose 6-phosphate dehydrogenase-deficient donor blood leads to a lesser drop in
      postexchange total serum bilirubin. It prolongs the duration of phototherapy and
      increases the need for repeat exchange transfusions.

PMID- 19103676
TI  - Interhemispheric inhibition between primary motor cortices: what have we learned?

PMID- 19103677
TI  - The late gestation fetal cardiovascular response to hypoglycaemia is modified by
      prior peri-implantation undernutrition in sheep.
AB  - Undernourished late gestation fetuses display asymmetric growth restriction,
      suggestive of a redistribution of nutritional resources. The modification of
      fetal organ blood supply in response to acute hypoxia is well characterized, but
      it is not known whether similar responses occur in response to acute reductions
      in nutrition, or if such late gestation responses can be influenced by early
      gestation nutrition. In pregnant sheep, total nutrient requirements were
      restricted during the peri-implantation period (PI40, 40%; PI50, 50% of total,
      days 1-31) or in late gestation (L, 50% total, days 104-postmortem). Control
      animals were fed 100% nutrient requirements. Fetal organ blood flows were
      measured at baseline, and during acute fetal hypoglycaemia induced by maternal
      insulin infusion at 125 dGA. Baseline heart rate was increased in PI40 fetuses.
      During hypoglycaemia, an initial rise in fetal heart rate was followed by a
      slower fall. Fetal femoral artery blood flow decreased, and adrenal blood flow
      and femoral vascular resistance increased in all fetuses during hypoglycaemia.
      These changes were accompanied by increased fetal plasma adrenaline and cortisol,
      and reduced plasma insulin levels. The maximum femoral artery blood flow response
      to hypoglycaemia occurred earlier in PI50 and PI40 compared with control fetuses.
      The late gestation fetal cardiovascular response to acute hypoglycaemia was
      consistent with a redistribution of combined ventricular output away from the
      periphery and towards central organs. One element of the peripheral vascular
      response was modified by peri-implantation nutrient restriction, indicating that
      nutritional challenges early in gestation can have an enduring impact on
      cardiovascular control.

PMID- 19103679
TI  - Gadolinium inhibits group III but not group IV muscle afferent responses to
      dynamic exercise.
AB  - Dynamic exercise has been shown to stimulate rapidly both group III and IV muscle
      afferents. The often rapid (i.e. 2 s) onset latencies of the group IV afferents
      is particularly surprising because these unmyelinated afferents are thought to
      respond to the gradual accumulation of metabolites signalling a mismatch between
      blood/oxygen demand and supply in exercising muscles. One explanation for the
      rapid onset to exercise by group IV afferents is that they are mechanosensitive,
      a concept that has been supported by the finding that these afferents were
      stimulated by vasodilatation induced by injection of vasoactive drugs. We
      therefore examined in decerebrated cats the effect of gadolinium, a blocker of
      mechanogated channels, on the responses of group III and IV muscle afferents to
      dynamic exercise induced by electrical stimulation of the mesencephalic locomotor
      region. We found that gadolinium (10 mm; 1 ml) injected into the abdominal aorta
      had no significant effect (P > 0.05) on the responses of 11 group IV afferents to
      dynamic exercise. In contrast, gadolinium markedly attenuated the responses of 11
      group III afferents to exercise (P < 0.05). Our findings suggest that group IV
      afferents are not responding to a mechanical stimulus during exercise. Instead
      their rapid response to dynamic exercise might be caused by a chemical substance
      whose concentration is directly proportional to blood flow, which increases in
      the skeletal muscles when they are dynamically exercising.

PMID- 19103678
TI  - Characteristics and function of cardiac mitochondrial nitric oxide synthase.
AB  - We used laser scanning confocal microscopy in combination with the nitric oxide
      (NO)-sensitive fluorescent dye DAF-2 and the reactive oxygen species (ROS)
      sensitive dyes CM-H(2)DCF and MitoSOX Red to characterize NO and ROS production
      by mitochondrial NO synthase (mtNOS) in permeabilized cat ventricular myocytes.
      Stimulation of mitochondrial Ca(2+) uptake by exposure to different cytoplasmic
      Ca(2+) concentrations ([Ca(2+)](i) = 1, 2 and 5 microm) resulted in a dose
      dependent increase of NO production by mitochondria when L-arginine, a substrate
      for mtNOS, was present. Collapsing the mitochondrial membrane potential with the
      protonophore FCCP or blocking the mitochondrial Ca(2+) uniporter with Ru360 as
      well as blocking the respiratory chain with rotenone or antimycin A in
      combination with oligomycin inhibited mitochondrial NO production. In the absence
      of L-arginine, mitochondrial NO production during stimulation of Ca(2+) uptake
      was significantly decreased, but accompanied by increase in mitochondrial ROS
      production. Inhibition of mitochondrial arginase to limit L-arginine availability
      resulted in 50% inhibition of Ca(2+)-induced ROS production. Both mitochondrial
      NO and ROS production were blocked by the nNOS inhibitor (4S)-N-(4-amino
      5[aminoethyl]aminopentyl)-N'-nitroguanidine and the calmodulin antagonist W-7,
      while the eNOS inhibitor L-N(5)-(1-iminoethyl)ornithine (L-NIO) or iNOS inhibitor
      N-(3-aminomethyl)benzylacetamidine, 2HCl (1400W) had no effect. The superoxide
      dismutase mimetic and peroxynitrite scavenger MnTBAP abolished Ca(2+)-induced ROS
      generation and increased NO production threefold, suggesting that in the absence
      of MnTBAP either formation of superoxide radicals suppressed NO production or
      part of the formed NO was transformed quickly to peroxynitrite. In the absence of
      L-arginine, mitochondrial Ca(2+) uptake induced opening of the mitochondrial
      permeability transition pore (PTP), which was blocked by the PTP inhibitor
      cyclosporin A and MnTBAP, and reversed by L-arginine supplementation. In the
      presence of the mtNOS cofactor (6R)-5,6,7,8,-tetrahydrobiopterin (BH(4); 100
      microm) mitochondrial ROS generation and PTP opening decreased while
      mitochondrial NO generation slightly increased. These data demonstrate that
      mitochondrial Ca(2+) uptake activates mtNOS and leads to NO-mediated protection
      against opening of the mitochondrial PTP, provided sufficient availability of l
      arginine and BH(4). In conclusion, our data show the importance of L-arginine and
      BH(4) for cardioprotection via regulation of mitochondrial oxidative stress and
      modulation of PTP opening by mtNOS.

PMID- 19103680
TI  - Neuronal oscillations and the rate-to-phase transform: mechanism, model and
      mutual information.
AB  - Theoretical and experimental studies suggest that oscillatory modes of processing
      play an important role in neuronal computations. One well supported idea is that
      the net excitatory input during oscillations will be reported in the phase of
      firing, a 'rate-to-phase transform', and that this transform might enable a
      temporal code. Here, we investigate the efficiency of this code at the level of
      fundamental single cell computations. We first develop a general framework for
      the understanding of the rate-to-phase transform as implemented by single
      neurons. Using whole cell patch-clamp recordings of rat hippocampal pyramidal
      neurons in vitro, we investigated the relationship between tonic excitation and
      phase of firing during simulated theta frequency (5 Hz) and gamma frequency (40
      Hz) oscillations, over a range of physiological firing rates. During theta
      frequency oscillations, the phase of the first spike per cycle was a near-linear
      function of tonic excitation, advancing through a full 180 deg, from the peak to
      the trough of the oscillation cycle as excitation increased. In contrast, this
      relationship was not apparent for gamma oscillations, during which the phase of
      firing was virtually independent of the level of tonic excitatory input within
      the range of physiological firing rates. We show that a simple analytical model
      can substantially capture this behaviour, enabling generalization to other
      oscillatory states and cell types. The capacity of such a transform to encode
      information is limited by the temporal precision of neuronal activity. Using the
      data from our whole cell recordings, we calculated the information about the
      input available in the rate or phase of firing, and found the phase code to be
      significantly more efficient. Thus, temporal modes of processing can enable
      neuronal coding to be inherently more efficient, thereby allowing a reduction in
      processing time or in the number of neurons required.

PMID- 19103681
TI  - Maternal nutritional history predicts obesity in adult offspring independent of
      postnatal diet.
AB  - Significant alterations in maternal nutrition may induce long-term metabolic
      consequences in offspring, in particular obesity and leptin and insulin
      resistance. Although maternal nutrient deprivation has been well characterized in
      this context, there is a relative paucity of data on how high fat (HF) nutrition
      impacts on the subsequent generation. The present study investigated the effects
      of maternal HF nutrition either throughout the mother's life up to and including
      pregnancy and lactation or HF nutrition restricted to pregnancy and lactation, on
      growth and metabolic parameters in male and female offspring. Virgin Wistar rats
      were assigned to one of three experimental groups: (1) controls (Cont): dams fed
      a standard chow diet throughout their life and throughout pregnancy and
      lactation; (2) maternal high fat (MHF) group: dams fed a HF diet from weaning up
      to and throughout pregnancy and lactation; and (3) pregnancy and lactation high
      fat (PLHF): dams fed a chow diet through their life until conception and then fed
      a HF diet throughout pregnancy and lactation. At weaning, all offspring were fed
      either a chow or HF diet for the remainder of the study (160 days). Litter size
      and sex ratios were not significantly different between the groups. MHF and PLHF
      offspring had significantly lower body weights and were hypoleptinaemic and
      hypoinsulinaemic at birth compared to Cont offspring. As adults however, chow-fed
      MHF and PLHF offspring were significantly more obese than Cont offspring (DEXA
      scanning at day 150, P < 0.001 for maternal HF diet). As expected a postweaning
      HF diet resulted in increased adiposity in all groups; MHF and PLHF offspring,
      however, always remained significantly more obese than Cont offspring. Increased
      adiposity in MHF and PLHF offspring was paralleled by hyperinsulinaemia and
      hyperleptinaemia (P < 0.001; MHF and PLHF versus Cont). It is of interest that a
      lifetime of HF nutrition produced a similar offspring phenotype to HF nutrition
      restricted to pregnancy and lactation alone, thus suggesting that the postnatal
      sequelae of maternal HF nutrition occurs independent of preconceptional diet.
      These data further reinforce the importance of maternal nutrition during these
      critical windows of development and show that maternal HF feeding can induce a
      markedly obese phenotype in male and female offspring completely independent of
      postnatal nutrition.

PMID- 19103682
TI  - Physiological properties of direction-selective ganglion cells in early postnatal
      and adult mouse retina.
AB  - Selective responses of retinal ganglion cells (RGCs) to the direction of motion
      have been recorded extracellularly from the rabbit and the mouse retina at eye
      opening. Recently, it has been shown that the development of this circuitry is
      light independent. Using whole-cell patch clamp recording, we report here that
      mouse early postnatal direction-selective ganglion cells (DSGCs) showed lower
      membrane excitability, lower reliability of synaptic transmission and much slower
      kinetics of light responses compared with adult DSGCs. However, the degree of
      direction selectivity of early postnatal DSGCs measured by the direction
      selective index and the width of the directional tuning curve was almost
      identical to that of adult DSGCs. The DSGCs exhibited a clear selectivity for the
      direction of motion at the onset of light sensitivity. Furthermore, the degree of
      direction selectivity was not affected by rearing in complete darkness from birth
      to postnatal day 11 or 30. The formation of the retinal neurocircuitry for coding
      motion direction is completely independent of light.

PMID- 19103685
TI  - Workplace stressors and satisfiers.

PMID- 19103683
TI  - Synaptic ionotropic glutamate receptors and plasticity are developmentally
      altered in the CA1 field of Fmr1 knockout mice.
AB  - Fragile X syndrome is one of the most common forms of mental retardation, yet
      little is known about the physiological mechanisms causing the disease. In this
      study, we probed the ionotropic glutamate receptor content in synapses of
      hippocampal CA1 pyramidal neurons in a mouse model for fragile X (Fmr1 KO2). We
      found that Fmr1 KO2 mice display a significantly lower AMPA to NMDA ratio than
      wild-type mice at 2 weeks of postnatal development but not at 6-7 weeks of age.
      This ratio difference at 2 weeks postnatally is caused by down-regulation of the
      AMPA and up-regulation of the NMDA receptor components. In correlation with these
      changes, the induction of NMDA receptor-dependent long-term potentiation
      following a low-frequency pairing protocol is increased in Fmr1 KO2 mice at this
      developmental stage but not later in maturation. We propose that ionotropic
      glutamate receptors, as well as potentiation, are altered at a critical time
      point for hippocampal network development, causing long-term changes. Associated
      learning and memory deficits would contribute to the fragile X mental retardation
      phenotype.

PMID- 19103686
TI  - Dedicated charities for survivors of torture and organized violence.

PMID- 19103684
TI  - A negative interaction between brainstem and peripheral respiratory
      chemoreceptors modulates peripheral chemoreflex magnitude.
AB  - Interaction between central (brainstem) and peripheral (carotid body) respiratory
      chemosensitivity is vital to protect blood gases against potentially deleterious
      fluctuations, especially during sleep. Previously, using an in situ arterially
      perfused, vagotomized, decerebrate preparation in which brainstem and peripheral
      chemoreceptors are perfused separately (i.e. dual perfused preparation; DPP), we
      observed that the phrenic response to specific carotid body hypoxia was larger
      when the brainstem was held at 25 Torr P(CO(2)) compared to 50 Torr P(CO(2)).
      This suggests a negative (i.e. hypo-additive) interaction between chemoreceptors.
      The current study was designed to (a) determine whether this observation could be
      generalized to all carotid body stimuli, and (b) exclude the possibility that the
      hypo-additive response was the simple consequence of ventilatory saturation at
      high brainstem P(CO(2)). Specifically, we tested how steady-state brainstem
      P(CO(2)) modulates peripheral chemoreflex magnitude in response to carotid body
      P(CO(2)) and P(O(2)) perturbations, both above and below eupnoeic levels. We
      found that the peripheral chemoreflex was more responsive the lower the brainstem
      P(CO(2)) regardless of whether the peripheral chemoreceptors received stimuli
      which increased or decreased activation. These findings demonstrate a negative
      interaction between brainstem and peripheral chemosensitivity in the rat in the
      absence of ventilatory saturation. We suggest that a negative interaction in
      humans may contribute to increased controller gain associated with sleep-related
      breathing disorders and propose that the assumption of simple addition between
      chemoreceptor inputs used in current models of the respiratory control system be
      reconsidered.

PMID- 19103687
TI  - Caring for undernourished patients in an orthopaedic setting.
AB  - This study elucidates the nursing of undernourished patients as experienced by
      eight registered clinical nurses and five nursing assistants by using content
      analysis. The participants' narratives describe the inner perspective of caring
      for undernourished patients, known in Sweden as 'the thin ones'. Categories
      identified were: frustration in nursing, joy in nursing and that undernourishment
      is taboo. The taboo was narrated as feelings of guilt and shame. Frustration in
      nursing could be seen as feeling stressed, exposed, lonely, powerless, helpless,
      and being torn between demands and needs. Joy in nursing was experienced when
      creating a trusting relationship, promoting pleasure in the meal situation and
      working with respect for each individual's life-style and context of life.
      Understanding staff members' views is important when implementing guidelines as
      well as in the teaching situation in order to identify where staff stand with
      regard to knowledge and attitudes.

PMID- 19103688
TI  - Spiritual job satisfaction in an Iranian nursing context.
AB  - This article reports the results of a qualitative study that used a deep
      interview method. The aim was to gather lived experiences of clinical nurses
      employed at government-funded medical centres regarding the non-materialistic and
      spiritual aspects of the profession that have had an important impact on their
      job satisfaction. On analysing the participants' concepts of spiritual
      satisfaction, the following themes were extracted: spiritually pleasant feelings,
      patients as celestial gifts, spiritual commitment, spiritual penchant, spiritual
      rewards, and spiritual dilemmas. Content analysis of the data indicated that
      nurses who viewed these dimensions of job satisfaction as a significant factor
      considered nursing as an opportunity to worship God while providing care for
      patients, and regarded their aim as achieving patients' contentment by providing
      nursing care compatible with scientific care methods.

PMID- 19103689
TI  - The influence of conscience in nursing.
AB  - The influence of conscience on nurses in terms of guilt has frequently been
      described but its impact on care has received less attention. The aim of this
      study was to describe nurses' conceptions of the influence of conscience on the
      provision of inpatient care. The study employed a phenomenographic approach and
      analysis method. Fifteen nurses from three hospitals in western Sweden were
      interviewed. The results showed that these nurses considered conscience to be an
      important factor in the exercise of their profession, as revealed by the
      descriptive categories: conscience as a driving force; conscience as a
      restricting factor; and conscience as a source of sensitivity. They perceived
      that conscience played a role in nursing actions involving patients and next of
      kin, and was an asset that guided them in their efforts to provide high quality
      care.

PMID- 19103690
TI  - Nurses' (un)partner-like relationships with clients.
AB  - The aim of a previous study was to describe nursing in Slovenia generally, and to
      identify the most appropriate nursing model for that country. One specific
      finding was the issue of partner-like relationships; this article deals with that
      issue only. An interpretive paradigm and qualitative research design were used
      with a modified grounded theory approach. Interviews were carried out with
      selected nursing leaders (n = 24) and other professionals (n = 6) in order to
      draw on their knowledge and experience to describe the reality of nursing
      phenomena. The results of this research suggest that participants wish to use a
      theory that emphasizes clients and treats them as equal partners in nursing,
      promotes health, and rests on interpersonal relationships. The participants
      described the missing or obscure parts in nursing and their own beliefs and
      values about human beings and nursing. Descriptions of and the need for partner
      like relationships, and the specific elements of such relationships, were of main
      concern. The participants argued that nurses need high quality and continuing
      education to ensure competent nursing practice. The indication is that Slovenia
      should move to graduate and undergraduate nurse education to foster expert
      reflective practice in order to abolish routinized care carried out in a
      hierarchical system.

PMID- 19103691
TI  - An overview of moral distress and the paediatric intensive care team.
AB  - A summary of the existing literature related to moral distress (MD) and the
      paediatric intensive care unit (PICU) reveals a high-tech, high-pressure
      environment in which effective teamwork can be compromised by MD arising from
      different situations related to: consent for treatment, futile care, end-of-life
      decision making, formal decision-making structures, training and experience by
      discipline, individual values and attitudes, and power and authority issues.
      Attempts to resolve MD in PICUs have included the use of administrative tools
      such as shift worksheets, the implementation of continuing education, and
      encouragement to report. The literature does not yet show these approaches to be
      effective in the resolution of MD. The need to acknowledge MD among PICU teams is
      discussed and an argument made that, to facilitate understanding among team
      members, practice stories need to be shared.

PMID- 19103692
TI  - Nurse educators' and nursing students' perspectives on teaching codes of ethics.
AB  - Professional codes of ethics are regarded as elements of nurses' ethical
      knowledge base and consequently part of their ethics education. However, research
      focusing on these codes from an educational viewpoint is scarce. This study
      explored the need and applicability of nursing codes of ethics in modern health
      care, their importance in the nursing ethics curriculum, and the need for
      development of their teaching. A total of 183 Finnish nurse educators and 212
      nursing students answered three structured questions, with an opportunity to
      justify their responses, and one open-ended question. Descriptive statistics and
      content analysis were used to analyse the data. The results suggest that the
      existence of the codes was seen as important and their applicability mainly as
      appropriate, despite new challenges posed by modern health care. The codes were
      regarded as an important part of nurses' ethics education, but current integrated
      teaching methods require development.

PMID- 19103693
TI  - Attitudes to end-of-life decisions in paediatric intensive care.
AB  - The aim of this study was to assess attitudes of intensive care nurses to
      selected ethical issues related to end-of-life decisions in paediatric intensive
      care units. A self-administered questionnaire was distributed in 2005 to
      intensive care nurses at two different scientific occasions in Turkey. Of the 155
      intensive care nurse participants, 98% were women. Fifty-three percent of these
      had intensive care experience of more than four years. Most of the nurses failed
      to agree about withholding (65%) or withdrawing (60%) futile treatment. In
      addition, 68% agreed that intravenous nutrition must continue at all costs. In
      futile treatment cases, the nurses tended to leave the decision to parents or act
      maternalistically. The results showed that intensive care nurses could ignore
      essential ethical duties in end-of-life care. We suggest that it is necessary to
      educate Turkish intensive care nurses about ethical issues at the end of life.

PMID- 19103694
TI  - Advance directives and proxies' predictions about patients' treatment
      preferences.
AB  - The accuracy of proxies when they interpret advance directives or apply
      substituted decision-making criteria has been called into question. It therefore
      became important to know if the Andalusian Advance Directive Form (AADF) can help
      to increase the accuracy of proxies' predictions. The aim of this research was to
      compare the effect of the AADF on the accuracy of proxies' predictions about
      patients' preferences with that gained from informative and deliberative sessions
      about end-of-life decision making. A total of 171 pairs of patients and their
      proxies were randomized to three groups. The control group's answers to the Life
      Sustaining Preferences Questionnaire (LSPQ) were compared with their proxies'
      answers to the same questionnaire. In one intervention group, the patients had
      already completed the AADF and given it to their proxies, who used it to guide
      their own answers to the LSPQ. In the second intervention (discussion) group,
      both patients and proxies attended two educative sessions guided by trained
      nurses and later filled in the LSPQ. Comparisons of accuracy and other variables
      showed a strong association with the discussion group. The findings show that
      promoting communication between patients and their proxies improves the accuracy
      of proxies' predictions much more than isolated use of the AADF form.

PMID- 19103695
TI  - Elder abuse and mistreatment in residential settings.
AB  - Older people living in a residential setting have the right to respectful care
      based on professional ethics. The aim of this study was to describe employees'
      and clients' lived experiences of elder abuse. A qualitative phenomenological
      method was used with 26 employees and 20 residents from four homes for elderly
      people in the town of Ostrava, Czech Republic, and two managers from outside
      these institutions. All complaints about elder abuse (n 5 11) received by Ostrava
      Municipal Authority during the period 2003 to 2007 were examined. Two main
      dimensions of the examined phenomenon were identified: forms of elder abuse and
      causes of elder abuse. Established forms of elder abuse were summarized as rights
      violation, financial abuse, psychological abuse, physical abuse and neglect.
      Causes of elder abuse included institution, employee and client characteristics.
      It is necessary in residential settings to create preventive policies that will
      focus on supervision regarding elderly people's rights violation and
      psychological and physical abuse, as well as on building organizational cultures
      that will respect ethical principles.

PMID- 19103696
TI  - The twins: a case study in ethical deliberation.
AB  - A case study of an ethical dilemma concerning twin nine-year-old sisters in a
      persistent vegetative state is presented. This is illustrated by the use of a
      systematic ethical framework to examine the case and the resolution, which was
      ultimately obtained with nurse-parent interrelations, using the human becoming
      nursing theory.

PMID- 19103697
TI  - Nursing ethics and health care policy: bridging local, national and international
      perspectives: ICNE conference, Yale University, New Haven, CT, USA; 17--19 July
      2008.

PMID- 19103698
TI  - Reflections on 2008.

PMID- 19103700
TI  - Research findings and case studies elaborate the experiences of clients and
      professionals in very different areas of work.

PMID- 19103701
TI  - Editorial: be (a) patient.

PMID- 19103702
TI  - The diagnosis of Tourette's Syndrome: communication and impact.
AB  - No study to date has investigated differences in perception regarding the manner
      in which a diagnosis of Tourette's Syndrome (TS) is communicated and the impact
      that this diagnosis can have on patients, as well as their relatives and
      physicians. The main objective was to explore the personal experiences regarding
      the communication and impact of a TS diagnosis on those who receive the
      diagnosis, their caregivers and physicians. A qualitative research methodology
      was used in this study, based on the use of focus groups (FGs). All health
      professionals, persons with TS and their relatives said that TS was difficult to
      diagnose. However, each group perceived different causes for the difficulty.
      Physicians cited the complexity of the symptoms, while the patients themselves
      noted the general lack of knowledge regarding the disease. In adittion, the
      physicians and the relatives both noted that the symptoms of TS were often hidden
      behind family guilt. The communication of the diagnosis to relatives of children
      with TS was not adequate because of poor understanding and interpretation of the
      clinical terminology. The most important conclusion was that the current method
      for communicating the diagnosis of TS to patients and relatives should be
      improved to facilitate better understanding and interpretation.

PMID- 19103703
TI  - At-risk mothers' parenting capacity: an epistemological analysis of change
      through intensive intervention.
AB  - Using an epistemological framework, we examine the process of change for two at
      risk mothers participating in the Children's Ark, an innovative foster care
      program. The Children's Ark invited at-risk mothers who had lost custody of their
      children to live in a structured, supervised environment with their
      infants/toddlers while receiving intensive intervention. Focusing on two mothers
      who completed the program and regained custody of their children, we developed a
      coding system from Women's ways of knowing (Belenky, Clinchy, Goldberger, &
      Tarule, 1986) to analyze entry and discharge interviews, and as a means of
      exploring alternative conceptualizations to the helping professions'
      understanding of at-risk families. In terms of an epistemological framework, we
      found that mothers increased their capacity to acknowledge their own minds and
      voices and those of their children. Additionally, mothers came to recognize their
      capacity to generate knowledge, especially through dialogue and relationships
      with others. In conclusion, we discuss the utility of an epistemological
      perspective in describing and exploring change in at-risk mothers, including
      possible implications for practice.

PMID- 19103704
TI  - Young offenders' experiences of traumatic life events: a qualitative
      investigation.
AB  - This investigation aimed to look at how a group of young offenders attending an
      inner-city youth offending team experienced adverse and traumatic life events. A
      qualitative approach was used and semi-structured interviews were conducted with
      eight young offenders about their perceptions of difficult experiences and the
      effects of such events. The interviews were analysed using Interpretative
      Phenomenological Analysis (Smith, Jarman, & Osborn, 1999). Analysis of the
      accounts yielded a number of themes. Young offenders experienced violence at
      home, in the community and in custody. Instability and transitions emerged as
      important themes in relation to school and home. Deprivation was experienced both
      in terms of poverty and the literal and emotional absence of parents. A variety
      of cognitive, emotional and behavioural responses to adverse/traumatic
      experiences were identified, including a blocking out of painful experience and
      aggression to self and others. There were barriers to seeking or making use of
      professional support. Custody appeared to offer an opportunity to reflect on and
      re-evaluate life trajectory. The study concluded that greater consideration of
      trauma when carrying out assessments would enable ;at risk' young offenders to be
      identified using clinical interviewing along side standardized measures to aid
      assessment of the complexity and uniqueness of the response to trauma.

PMID- 19103705
TI  - Life-threatening food refusal in two nine-year-old girls: re-thinking the
      Maudsley model.
AB  - While there is growing evidence for the efficacy of the Maudsley model of family
      based treatment for anorexia nervosa, little is known concerning the most
      effective treatment for pre-adolescents with Eating Disorders Not Otherwise
      Specified (EDNOS). The presentation of case studies of children with EDNOS is
      important. Large-scale studies are difficult due to low incidence and the
      application of homogenous manualized approaches may be unsuitable to the wide
      range of potential disorders. The aim of this article is to present two detailed
      case studies of children with food avoidant emotional disorder, both presenting
      with life threatening food refusal. A flexible and individualized approach to
      family therapy was taken, resulting in the resumption of eating in less than
      seven weeks and four months respectively.

PMID- 19103707
TI  - Characterizing anxious children with an obsessive difficult temperament.
AB  - This exploratory study sought to characterize anxious children displaying an
      Obsessive Difficult Temperament (ODT), and examined features that may
      differentiate them from anxiety disordered, non ODT children. Participants
      comprised 67 children, aged 4 to 7 years, consecutively referred to an anxiety
      disorders clinic at an urban children's hospital. Retrospective categorization of
      the participants' temperament profile was undertaken, with 21 children appearing
      to display ODT. Groups were compared on the bases of child functioning (parent
      and clinician rated), the presence of comorbid disorders (based on structured
      interview), and parental stress and symptomatology. Participants with ODT were
      found to display a specific profile of temperament traits. Compared to non ODT
      participants, they showed a significantly poorer social functioning, more
      comorbid externalizing disorders, elevated levels of maternal stress, and
      increased maternal psychiatric symptoms. To conclude, anxious children expressing
      ODT present with significant impairments in functioning and require further
      investigation. Associated parental stress and impaired maternal psychosocial
      functioning are evident.

PMID- 19103706
TI  - Guilt and posttraumatic stress symptoms in child victims of interpersonal
      violence.
AB  - Our objective was to examine the relationship between guilt and posttraumatic
      stress disorder (PTSD) symptoms in children with a history of interpersonal
      violence. Eighty-seven children between the ages of 5 and 16 years (mean age =
      11.70 years) were administered the Clinician-Administered PTSD Scale for Children
      and Adolescents to assess for PTSD symptoms and associated features. Multiple
      regression analysis found that guilt over acts of commission or omission
      (behaviors the child performed or failed to perform during the event or to
      prevent it) was highly associated with PTSD severity. Derealization and changes
      in attachment were also significantly related to PTSD symptoms. Findings suggest
      that it may be important for clinicians to assess for associated features in
      traumatized children as these are associated with greater PTSD severity.
      Posttraumatic interventions may benefit from targeting these symptoms.

PMID- 19103708
TI  - Exploring young women's understandings of the development of difficulties: a
      narrative biographical analysis.
AB  - This article describes a qualitative research study which used in-depth
      interviews to elicit young women's narratives about the meanings they hold
      regarding the important experiences in their lives, and their understandings of
      the development of difficulties that have led them to be in contact with Child
      and Adolescent Mental Health Services (CAMHS). Five young women (aged 15-17
      years) who were current users of CAMHS were interviewed. A narrative analysis was
      conducted on the data. The findings revealed how contact with services may have
      impacted on their developing sense of self during this important transitional
      period of their lives. The young women's stories differed in the extent to which
      they drew on themes of difficulties as indicators of illness or the result of
      difficult life events. Their sense-making appeared to be influenced by the
      relationships, contexts and discourses which they were exposed to and embedded
      within.

PMID- 19103709
TI  - The perpetuation of patriarchy: the hidden factor of gender bias in the diagnosis
      and treatment of children.
AB  - The history of the mental health movement suggests that political and economic
      forces often have undue influence on the science of nosology. Given this
      situation, diagnostic categories which are applied disproportionately to a
      particular population segment may warrant reconsideration. While many scholars
      have questioned why a number of adult diagnostic categories are used
      disproportionately with females, few have examined why the diagnostic categories
      for children are applied with greater frequency to males. The authors suggest
      that gender bias in the diagnosis and treatment of children ultimately serves to
      foster patriarchy, by reinforcing existing patterns of maternal child rearing
      rather than promoting the goal of shared parenting.

PMID- 19103711
TI  - Soapbox: in defence of weakness.

PMID- 19103713
TI  - Fear, complacency and the spectacle of risk: the making of HIV as a public
      concern in Australia.
AB  - This article explores how HIV is constituted as a matter of public concern in
      Australia, where - unlike much of the rest of the world - there is a continuing
      low incidence of heterosexual transmission. In this context, it is timely to
      explore how the media contributes to the ongoing mobilization of public interest
      in HIV, and how heterosexual audiences are brought into focus as the imagined
      ;publics' of mainstream debates on HIV. This article identifies three approaches
      to generating public concern in HIV news stories published in The Sydney Morning
      Herald between 2000 and 2005 as well as in academic media analysis and HIV
      education and advocacy. Reflections on fear revisit the early years of the
      epidemic, distinguishing a generation of Australian audiences shaped by the Grim
      Reaper campaign. Encounters with complacency focus on an apparently widespread
      lack of concern about HIV in the present. And projections in risk forecast a
      multiplication of HIV risk environments, despite confusion about who should be
      personally concerned about those risks. Together they construct Australian
      publics as passive, vulnerable, unaware and potentially uncaring, yet do little
      to engage the mainstream as more than spectators of public concern about HIV.

PMID- 19103714
TI  - Intimate relationships and women involved in the sex trade: perceptions and
      experiences of inclusion and exclusion.
AB  - This article reports on a qualitative study exploring the intimate (non-work)
      relationships of women involved in the sex trade. Women working in the sex
      industry and intimate partners of women in the industry were interviewed in order
      to understand how intimate relationships are perceived as influencing the women's
      general health and well-being. The research suggests that intimate relationships
      can, and do, provide a space for feelings of inclusion and safety that are
      perceived as positive forces in women's general health and well-being. At the
      same time, however, feelings and experiences of exclusion (fuelled by the
      dominant stigmatizing discourse related to prostitution) can enter into intimate
      relationships, and are perceived as having a negative impact on the women's well
      being, particularly their emotional health. Although there are attempts to keep
      the women's work separate from the intimate relationship, cross-over between the
      two spheres does occur. The research suggests that health care and service
      providers need to look beyond the women's working lives, and understand the
      relationships between work and home, as well as the ways in which intimate
      relationships can influence women's lives and health through both positive and
      negative forces.

PMID- 19103715
TI  - Humanizing HIV/AIDS and its (re)stigmatizing effects: HIV public 'positive'
      speaking in India.
AB  - Social stigma has been inextricably linked with HIV and AIDS since the epidemic
      erupted in the early 1980s. The stigma that has built up around HIV and AIDS is
      generally regarded as having a negative impact on the quality of life of HIV
      positive people and on general prevention efforts. Current attempts to combat HIV
      related stigma focus on increasing the acceptance of HIV among the stigmatizing
      public and stigmatized individuals alike. In this, the global HIV-positive
      community is being increasingly called upon to ;humanize' the virus, not least
      through public displays of HIV 'positive' health and public ;positive' speaking.
      This article critically explores the constitutive effects and inherent power
      relations of HIV Positive Speakers' Bureaus (PSBs) as a platform for such a
      display. Adopting a post-structuralist discourse analytic approach, we explore
      accounts of positive-speaking and HIV health from HIV-related non-government
      organizations in India and in PSB training manuals. In particular, we highlight
      ways in which positive-speaking in India can be seen to have significant
      (re)stigmatizing effects by way of ambivalent and hyper-real configurations of
      HIV 'positive' identity and life.

PMID- 19103716
TI  - Images, femininity and cancer: an analysis of an international patient education
      programme.
AB  - This article is an analysis of a cancer patient education programme run by
      cosmetic companies. I focus on an analysis of imagery, arguing that there are
      particular discursive elements that the cosmetic companies use in order to make
      productive the relationship between femininity and cancer. I contextualize this
      education programme by presenting the controversies regarding cosmetics as they
      relate to the growth of breast tumours. In doing so, I conclude that
      conversations and questions about a link between chemicals and cancer are
      subverted by both ;horror' narratives of cancer and the provocative use of
      standards of beauty. Such discursive dominance in patient education programmes
      makes it difficult to engage in a more public understanding of cancer growth as
      affected by cosmetic chemicals.

PMID- 19103717
TI  - Refusing the information paradigm: informed consent, medical research, and
      patient participation.
AB  - This article challenges the assumption that patient autonomy can best be assured
      by providing proper information through formalized procedures such as informed
      consent. We suggest that to understand and consider laypeople's ways of knowing
      and decision making, one has to move beyond the information paradigm and take
      into account a much broader context. Concretely, we investigate informed consent
      in connection with donating skin tissue remaining from medically indicated
      surgery. We use interviews with patients and observation protocols to analyse
      patients' perceptions and ways of making sense of informed consent beyond its
      bioethical ideal. Patients situate themselves in a larger system of solidarity,
      enroll in an overall positive image of science as a linear process of innovation
      oriented towards output, and simultaneously take a pragmatic stance towards
      hospital routines as a necessary passage point towards receiving good treatment.
      Because informed consent is one of the central articulations between the
      biomedical system and society, we conclude by reflecting on the consequences of
      our findings on a socio-political level.

PMID- 19103718
TI  - Communities of clinical practice: the social organization of clinical learning.
AB  - The social organization of clinical learning is under-theorized in the
      sociological literature on the social organization of health care. Professional
      scopes of practice and jurisdictions are formally defined by professional
      principles and standards and reflected in legislation; however, these are
      mediated through the day-to-day clinical activities of social groupings of
      clinical teams. The activities of health service providers typically occur within
      communities of clinical practice. These are also major sites for clinical
      curriculum delivery, where clinical students learn not only clinical skills but
      also how to be health professionals. In this article, we apply Wenger's model of
      social learning within organizations to curriculum delivery within a health
      service setting. Here, social participation is the basis of learning. We suggest
      that it offers a powerful framework for recognizing and explaining paradox and
      incongruence in clinical teaching and learning, and also for recognizing
      opportunities, and devising means, to add value to students' learning
      experiences.

PMID- 19103719
TI  - Functions of PIT1 in GATA2-dependent transactivation of the thyrotropin beta
      promoter.
AB  - Thyrotropin (TSH) is a heterodimer consisting of alpha and beta chains, and the
      beta chain (TSHbeta) is specific to TSH. The coexistence of two transcription
      factors, PIT1 and GATA2, is known to be essential for TSHbeta expression. Using
      kidney-derived CV1 cells, we investigated the role of PIT1 in the expression of
      Tshb gene. GATA2 Zn finger domain, which is known to recognize GATA-responsive
      elements (GATA-REs), is essential for cooperation by PIT1. Transactivation of
      TSHbeta promoter requires PIT1-binding site upstream to GATA-REs (PIT1-US), and
      the spacing between PIT1-US and GATA-REs strictly determines the cooperation
      between PIT1 and GATA2. Moreover, truncation of the sequence downstream to GATA
      REs enabled GATA2 to transactivate the TSHbeta promoter without PIT1. The deleted
      region (nt -82/-52) designated as a suppressor region (SR) was considered to
      inhibit transactivation by GATA2. The cooperation of PIT1 with GATA2 was not
      conventional synergism but rather counteracted SR-induced suppression
      (derepression). The minimal sequence for SR was mapped to the 9 bp sequence
      downstream to GATA-REs. Electrophoretic mobility shift assay suggested that some
      nuclear factor exists in CV1 cells, which binds with SR and this interaction was
      blocked by recombinant PIT1. Our study indicates that major activator for the
      TSHbeta promoter is GATA2 and that PIT1 protects the function of GATA2 from the
      inhibition by SR-binding protein.

PMID- 19103720
TI  - No evidence for a bone phenotype in GPRC6A knockout mice under normal
      physiological conditions.
AB  - GPRC6A is a seven-transmembrane receptor mediating signaling by a wide range of L
      alpha-amino acids, a signaling augmented by the divalent cations Ca(2)(+) and
      Mg(2)(+). GPRC6A transcripts are detected in numerous mammalian tissues, but the
      physiological role of the receptor is thus far elusive. Analogously to the
      closely related calcium-sensing receptor, GPRC6A has been proposed to function as
      a metabolic sensor of Ca(2)(+) and amino acids in bone and other tissues. In the
      present study, we have generated the first GPRC6A knockout mice and studied their
      phenotype with particular focus on bone homeostasis. The generated GPRC6A
      knockout mice are viable and fertile, develop normally, and exhibit no
      significant differences in body weight compared with wild-type littermates.
      Assessment of bone mineral density, histomorphometry, and bone metabolism
      demonstrated no significant differences between 13-week-old knockout and wild
      type mice. In conclusion, our data do not support a role for GPRC6A in normal
      bone physiology.

PMID- 19103721
TI  - Depressed recovery of subendocardial perfusion in persistent heart failure after
      complete revascularisation in diabetic patients with hibernating myocardium.
AB  - OBJECTIVES: To investigate the relation between myocardial perfusion and heart
      failure (HF) status after revascularisation in patients with HF due to
      hibernating myocardium (HM) in diabetic and non-diabetic subjects. METHODS: 31
      diabetic and 33 non-diabetic subjects with HF due to HM, who were already
      scheduled for complete revascularisation, were studied. Before and after
      revascularisation, left ventricular function and regional perfusion in
      subendocardial and subepicardial portions of the left ventricular wall were
      evaluated. RESULTS: Before revascularisation, left ventricular function and
      regional perfusion were similar in diabetic and non-diabetic subjects. At 6
      months after revascularisation, subepicardial perfusion was markedly improved
      both in diabetic and non-diabetic subjects. However, subendocardial perfusion was
      markedly improved only in non-diabetic subjects and was little changed in
      diabetic patients. Thus, subendocardial perfusion was much lower in diabetic than
      non-diabetic subjects. Left ventricular function was improved more in non
      diabetic than in diabetic subjects. Persistent HF was found much more often in
      diabetic than non-diabetic subjects. At multivariate analysis, subendocardial
      perfusion at 6 months independently contributed to persistent HF. CONCLUSIONS:
      This study describes the intramural heterogeneity of recovery of myocardial
      perfusion with depressed improvement in the subendocardial portion and its
      relation with persistent HF after complete revascularisation in diabetic patients
      with HF due to HM.

PMID- 19103722
TI  - Tyrosine kinase inhibitors and modifications of thyroid function tests: a review.
AB  - Tyrosine kinase inhibitors (TKI) belong to new molecular multi-targeted therapies
      that are approved for the treatment of haematological and solid tumours. They
      interact with a large variety of protein tyrosine kinases involved in
      oncogenesis. In 2005, the first case of hypothyroidism was described and since
      then, some data have been published and have confirmed that TKI can affect the
      thyroid function tests (TFT). This review analyses the present clinical and
      fundamental findings about the effects of TKI on the thyroid function. Various
      hypotheses have been proposed to explain the effect of TKI on the thyroid
      function but those are mainly based on clinical observations. Moreover, it
      appears that TKI could alter the thyroid hormone regulation by mechanisms that
      are specific to each molecule. The present propositions for the management of TKI
      induced hypothyroidism suggest that we assess the TFT of the patients regularly
      before and during the treatment by TKI. Thus, a better approach of patients with
      TKI-induced hypothyroidism could improve their quality of life.

PMID- 19103724
TI  - No association between hepatitis B and pancreatic cancer in a prospective study
      in Korea.

PMID- 19103723
TI  - Clinical cancer advances 2008: major research advances in cancer treatment,
      prevention, and screening--a report from the American Society of Clinical
      Oncology.
AB  - A message from ASCO'S president: Nearly 40 years ago, President Richard Nixon
      signed the National Cancer Act, mobilizing the country's resources to make the
      "conquest of cancer a national crusade." That declaration led to a major
      investment in cancer research that has significantly improved cancer prevention,
      treatment, and survival. As a result, two thirds of people diagnosed with cancer
      today will live at least 5 years after diagnosis, compared with just half in the
      1970s. In addition, there are now more than 12 million cancer survivors in the
      United States--up from 3 million in 1971. Scientifically, we have never been in a
      better position to advance cancer treatment. Basic scientific research, fueled in
      recent years by the tools of molecular biology, has generated unprecedented
      knowledge of cancer development. We now understand many of the cellular pathways
      that can lead to cancer. We have learned how to develop drugs that block those
      pathways; increasingly, we know how to personalize therapy to the unique genetics
      of the tumor and the patient. Yet in 2008, 1.4 million people in the United
      States will still be diagnosed with cancer, and more than half a million will die
      as a result of the disease. Some cancers remain stubbornly resistant to
      treatment, whereas others cannot be detected until they are in their advanced,
      less curable stages. Biologically, the cancer cell is notoriously wily; each time
      we throw an obstacle in its path, it finds an alternate route that must then be
      blocked. To translate our growing basic science knowledge into better treatments
      for patients, a new national commitment to cancer research is urgently needed.
      However, funding for cancer research has stagnated. The budgets of the National
      Institutes of Health and the National Cancer Institute have failed to keep pace
      with inflation, declining up to 13% in real terms since 2004. Tighter budgets
      reduce incentives to support high-risk research that could have the largest
      payoffs. The most significant clinical research is conducted increasingly
      overseas. In addition, talented young physicians in the United States, seeing
      less opportunity in the field of oncology, are choosing other specialties
      instead. Although greater investment in research is critical, the need for new
      therapies is only part of the challenge. Far too many people in the United States
      lack access to the treatments that already exist, leading to unnecessary
      suffering and death. Uninsured cancer patients are significantly more likely to
      die than those with insurance, racial disparities in cancer incidence and
      mortality remain stark, and even insured patients struggle to keep up with the
      rapidly rising cost of cancer therapies. As this annual American Society of
      Clinical Oncology report of the major cancer research advances during the last
      year demonstrates, we are making important progress against cancer. But sound
      public policies are essential to accelerate that progress. In 2009, we have an
      opportunity to reinvest in cancer research, and to support policies that will
      help ensure that every individual in the United States receives potentially life
      saving cancer prevention, early detection, and treatment. Sincerely, Richard L.
      Schilsky, MD President American Society of Clinical Oncology.

PMID- 19103725
TI  - Randomized, double-blind, placebo-controlled trial of epoetin alfa in men with
      castration-resistant prostate cancer and anemia.

PMID- 19103726
TI  - Mastering emasculation.

PMID- 19103727
TI  - Problems identified with phase II stopping rules that employ response and early
      progression rates.

PMID- 19103728
TI  - Complete cytoreductive surgery plus intraperitoneal chemohyperthermia with
      oxaliplatin for peritoneal carcinomatosis of colorectal origin.
AB  - PURPOSE: To compare the long-term survival of patients with isolated and
      resectable peritoneal carcinomatosis (PC) in comparable groups of patients
      treated with systemic chemotherapy containing oxaliplatin or irinotecan or by
      cytoreductive surgery plus hyperthermic intraperitoneal chemotherapy (HIPEC).
      PATIENTS AND METHODS: All patients with gross PC from colorectal adenocarcinoma
      who had undergone cytoreductive surgery plus HIPEC from 1998 to 2003 were
      evaluated. The standard group was constituted by selecting patients with
      colorectal PC treated with palliative chemotherapy during the same period, but
      who had not benefited from HIPEC because the technique was unavailable in the
      center at that time. RESULTS: Forty-eight patients were retrospectively included
      in the standard group and were compared with 48 patients who had undergone HIPEC
      and were evaluated prospectively. All characteristics were comparable except age
      and tumor differentiation. There was no difference in systemic chemotherapy, with
      a mean of 2.3 lines per patient. Median follow-up was 95.7 months in the standard
      group versus 63 months in the HIPEC group. Two-year and 5-year overall survival
      rates were 81% and 51% for the HIPEC group, respectively, and 65% and 13% for the
      standard group, respectively. Median survival was 23.9 months in the standard
      group versus 62.7 months in the HIPEC group (P < .05, log-rank test). CONCLUSION:
      Patients with isolated, resectable PC achieve a median survival of 24 months with
      modern chemotherapies, but only surgical cytoreduction plus HIPEC is able to
      prolong median survival to roughly 63 months, with a 5-year survival rate of 51%.

PMID- 19103729
TI  - Effect of recombinant adenovirus-p53 combined with radiotherapy on long-term
      prognosis of advanced nasopharyngeal carcinoma.
AB  - PURPOSE: To centrally assess the safety, efficacy, and 6-year follow-up of
      recombinant adenovirus-p53 (rAd-p53) combined with radiotherapy (RT) for patients
      with nasopharyngeal carcinoma (NPC). PATIENTS AND METHODS: A randomized
      controlled clinical study on rAd-p53 combined with RT in 42 patients with NPC was
      compared with a control group of 40 patients with NPC treated with RT alone. In
      the group receiving rAd-p53 combined with RT, rAd-p53 was intratumorally injected
      once a week for 8 weeks. Concurrent RT (70 Gy in 35 fractions) was given to the
      nasopharyngeal tumor and neck lymph node. Patients and tumors were monitored for
      adverse events and responses. RESULTS: rAd-p53-specific p53 mRNA was detected in
      postinjection of rAd-p53 biopsies from 16 (94.1%) of 17 patients. Upregulation of
      p21/WAF1 and Bax and downregulation of vascular endothelial growth factor were
      observed in postinjection tumor biopsy. Complete response rate in the group
      receiving rAd-p53 combined with RT was observed at 2.73 times that of the group
      receiving RT alone (66.7% v 24.4%). Six-year follow-up data showed that rAd-p53
      significantly increased the 5-year locoregional tumor control rate by 25.3% for
      patients with NPC treated with irradiation (P = .002). The 5-year overall
      survival rate and 5-year disease-free survival rate of the group receiving rAd
      p53 combined with RT were 7.5% (P = .34) and 11.7% (P = .21) higher than those of
      the group receiving RT alone. No dose-limiting toxicity or adverse events
      appeared, except for transient fever after rAd-p53 administration. CONCLUSION: In
      patients with NPC, rAd-p53 was safe and biologically active. Our results
      indicated that rAd-p53 improves radiotherapeutic tumor control and survival rate
      in patients with NPC.

PMID- 19103730
TI  - Clinical relevance of bone marrow fibrosis and CD34-positive cell clusters in
      primary myelodysplastic syndromes.
AB  - PURPOSE: We studied bone marrow (BM) histologic abnormalities in myelodysplastic
      syndromes (MDS) classified according to WHO criteria to determine their clinical
      correlates and prognostic value. PATIENTS AND METHODS: Three hundred one
      consecutive patients were retrospectively evaluated for BM fibrosis and CD34
      immunoreactivity. Marrow fibrosis was assessed following the European consensus
      guidelines. RESULTS: Moderate to severe BM fibrosis was detected in 17% of cases
      and was associated with multilineage dysplasia (P = .001), high transfusion
      requirement (P < .001), and poor-risk cytogenetics (P = .007). CD34+ cell
      clusters were found in 23% of patients and were associated with WHO categories
      with excess of blasts (P < .001) and poor-risk cytogenetics (P = .001). In
      multivariable analysis, BM fibrosis and presence of CD34+ cell clusters had
      independent negative impact on overall survival (P < .001 and P = .019,
      respectively) and leukemia-free survival (P < .001 and P = .004, respectively). A
      hierarchical clustering analysis identified three subsets of patients with
      distinct clinical features. One cluster consisted mainly of patients with BM
      fibrosis, multilineage dysplasia, and high transfusion requirement; these
      individuals had lower overall survival and leukemia-free survival (P = .001 and P
      < .001, respectively). Within patients stratified according to International
      Prognostic Scoring System and WHO classification-based Prognostic Scoring System
      categories, BM fibrosis involved a shift to a one-step more advanced risk group.
      CONCLUSION: BM fibrosis identifies a distinct subgroup of MDS with multilineage
      dysplasia, high transfusion requirement, and poor prognosis and represents an
      independent prognostic factor that may be useful in clinical decision making.
      Furthermore, the presence of CD34+ cell clusters is an independent risk factor
      for progression to acute leukemia.

PMID- 19103731
TI  - Trends in racial and age disparities in definitive local therapy of early-stage
      breast cancer.
AB  - PURPOSE: Guidelines recommend breast-conserving surgery (BCS) with radiation or
      mastectomy for definitive local therapy of stage I/II breast cancers. We assessed
      receipt of definitive local therapy for early-stage breast cancer by
      race/ethnicity and age and examined trends over time. PATIENTS AND METHODS: We
      calculated rates of definitive local therapy (mastectomy or BCS with radiation)
      for 375,547 adult women with stage I or II breast cancer diagnosed during 1988 to
      2004 using Surveillance, Epidemiology, and End Results registry data. We assessed
      the probability of definitive local therapy and trends over time using
      multivariate logistic regression. RESULTS: Overall, 85.8% of women had definitive
      local therapy. As mastectomy rates decreased (76.5% in 1988 to 38.0% in 2004; P <
      .001), definitive local therapy rates also decreased (95.2% in 1988 to 79.2% in
      2004; P < .001). In adjusted analyses, rates of definitive local therapy were
      modestly lower for black and Hispanic (v white) women and higher for Asian women.
      Differences for black and Asian women were stable over time (P = .61 and P = .35
      for interaction), but increased for Hispanic women (P = .0003). Although age
      differences narrowed over time, women older than 70 years and women <or= 60 years
      had lower rates of definitive local therapy than women 61 to 70 years throughout
      the study period. CONCLUSION: As breast conservation has increasingly substituted
      mastectomy, our findings suggest fewer women are receiving definitive local
      breast cancer therapy, with persistent disparities for black and Hispanic women
      as well as women age <or= 60 and older than 70 years. Interventions to assure
      receipt of radiation after BCS are needed to eliminate these disparities.

PMID- 19103732
TI  - Long-term benefit of high-dose epirubicin in adjuvant chemotherapy for node
      positive breast cancer: 15-year efficacy results of the Belgian multicentre
      study.
AB  - PURPOSE: The 4-year results of this trial demonstrated that a higher dose of
      epirubicin with cyclophosphamide (HEC) is superior to a lower dose of epirubicin,
      60 mg/m(2) (EC), for event-free survival (EFS; 27% reduction), but is not
      superior to classical oral cyclophosphamide, methotrexate, and fluorouracil (CMF)
      in the adjuvant treatment of node-positive breast cancer. Herein we report the 15
      year data on efficacy and long-term toxicity of this three-arm Belgian
      multicenter trial. PATIENTS AND METHODS: Between March 1988 and December 1996,
      777 eligible patients were randomly assigned to six cycles of CMF, eight cycles
      of EC, or eight cycles HEC. RESULTS: The 15-year EFS was 45% for patients who
      received CMF, 39% for patients who received EC, and 50% for patients who received
      HEC. The hazard ratios (HR) were 0.77 for HEC versus EC (95% CI, 0.60 to 0.98; P
      = .03), 0.90 for HEC versus CMF (P = .39), and 0.86 for EC versus CMF (P = .21).
      No difference in overall survival (OS) was seen. Cardiac toxicity was more
      frequent with HEC than with CMF (11 patients v 1 patient; P = .006), but no more
      than with EC (P = .21). CONCLUSION: Treatment with HEC demonstrated superior EFS
      when compared with lower-dose epirubicin. However, we do not recommend the use of
      HEC regimen in daily clinical practice, mainly because of the higher risk of
      cardiotoxicity related to the cumulative doses of epirubicin and the lack of
      superiority of anthracyclines over CMF in our study.

PMID- 19103733
TI  - Is pain intensity a predictor of the complexity of cancer pain management?
AB  - PURPOSE: The lack of a standardized cancer pain (CP) classification system
      prompted the development of the Edmonton Classification System for Cancer Pain
      (ECS-CP). Its five features have demonstrated value in predicting pain management
      complexity. Pain intensity (PI) at initial assessment has been proposed as having
      additional predictive value. We hypothesized that patients with moderate to
      severe CP would take longer to achieve stable pain control, use higher opioid
      doses, and require more complicated analgesic regimens than would patients with
      mild CP at initial assessment. METHODS: A secondary analysis of a multicenter ECS
      CP validation study involving patients with advanced cancer was conducted (n =
      591). Associations between PI and length of time to stable pain control (Cox
      regression), final opioid dose (Kruskal-Wallis one-way analysis of variance), and
      number of adjuvant modalities (chi(2)) were calculated. PI at initial assessment
      was defined using a numerical scale as mild (0 to 3), moderate (4 to 6), or
      severe (7 to 10). RESULTS: Patients with moderate and severe pain required a
      significantly longer time to achieve stable pain control (P < .0001). PI was a
      significant predictor of length of time to stable pain control in the univariate
      regression analysis. The four significant predictors in the multivariate model
      were moderate and severe PI (P < .0001), age (P = .001), and neuropathic pain (P
      = .002). Patients with moderate to severe pain required significantly higher
      final opioid doses (P < .0001) and more adjuvant modalities (P = .015).
      CONCLUSION: PI at initial assessment is a significant predictor of pain
      management complexity and length of time to stable pain control. Incorporation of
      this feature into the ECS-CP needs additional consideration.

PMID- 19103734
TI  - Association between delayed graft function and allograft and patient survival: a
      systematic review and meta-analysis.
AB  - BACKGROUND: Delayed graft function (DGF) is a common complication of renal
      transplantation. The short-term consequences of DGF are well known, but the long
      term relationship between DGF and patient and graft survival is controversial in
      the published literature. We conducted a systematic review and meta-analysis to
      precisely estimate these relationships. METHODS: We performed a literature search
      for original studies published through March 2007 pertaining to long-term (>6
      months) outcomes of DGF. The primary outcome was graft survival. Secondary
      outcomes were patient survival, acute rejection and kidney function. RESULTS:
      When compared to patients without DGF, patients with DGF had a 41% increased risk
      of graft loss (RR 1.41, 95% CI 1.27-1.56) at 3.2 years of follow-up. There was no
      significant relationship between DGF and patient survival at 5 years (RR 1.14,
      95% CI 0.94-1.39). The mean creatinine in the non-DGF group was 1.6 mg/dl.
      Patients with DGF had a higher mean serum creatinine (0.66 mg/dl, 95% CI 0.57
      0.74) compared to patients without DGF at 3.5 years of follow-up. DGF was
      associated with a 38% relative increase in the risk of acute rejection (RR 1.38,
      95% CI 1.29-1.47). CONCLUSION: The results of this meta-analysis emphasize and
      quantify the long-term detrimental association between DGF and important graft
      outcomes like graft survival, acute rejection and renal function. Efforts to
      prevent and treat DGF should be aggressively investigated in order to improve
      graft survival given the deficit in the number of kidney donors.

PMID- 19103735
TI  - Angiotensin II type 1 receptor expression is increased via 12-lipoxygenase in
      high glucose-stimulated glomerular cells and type 2 diabetic glomeruli.
AB  - BACKGROUND: Angiotensin II type 1 receptor (AT1) plays an important role in the
      development of diabetic nephropathy (DN). However, the roles played by 12
      lipoxygenase (12-LO) in the AT1 expression in glomerular cells exposed to high
      glucose (HG) and diabetic glomeruli remain unclear. Our objective in the present
      study was to investigate the role of 12-LO in the AT1 expression in glomerular
      cells and glomeruli under diabetic conditions. METHODS: Mesangial cells (MCs),
      podocytes and glomeruli isolated from rats were used in this study. The rats fed
      a high fat diet received low-dose streptozotocin to make type 2 diabetes. The 12
      LO product 12(S)-hydroxyeicosatetraenoic acid [12(S)-HETE] was infused to rats by
      osmotic mini-pump. Morphometric measurement for glomerular volume, competitive
      reverse transcription polymerase chain reaction for mRNA expression, western blot
      and immunohistochemistry for protein expression were performed, respectively.
      RESULTS: Both the 12(S)-HETE and HG increased AT1 protein expression in MCs and
      podocytes. Furthermore, the levels of the AT1 were significantly higher in
      glomeruli derived from 12(S)-HETE-treated rats compared with control rats. In
      addition, HG-induced AT1 expression was significantly reduced by the 12-LO
      inhibitor cinnamyl-3,4-dihydroxy-alpha-cynanocinnamate (CDC). Compared with the
      non-diabetic controls, DN rats showed significant glomerular hypertrophy and
      albuminuria. This was associated with significant increases in AT1 protein
      expression. These abnormalities were prevented by treatment of the CDC.
      CONCLUSIONS: These results indicate that AT1 expression is enhanced, at least in
      part, by 12-LO in the type 2 diabetic glomeruli, and 12-LO inhibition can
      ameliorate DN progression through downregulation of AT1 expression.

PMID- 19103736
TI  - A critical evaluation of chronic kidney disease--should isolated reduced
      estimated glomerular filtration rate be considered a 'disease'?

PMID- 19103737
TI  - Oxalate deposits in biopsies from native and transplanted kidneys, and impact on
      graft function.
AB  - BACKGROUND: The purpose of this study was to examine the incidence of oxalate
      deposits in native and renal allograft biopsies, and its impact on graft
      function. METHODS: The renal biopsy files at The Johns Hopkins University between
      2000 and 2006 were searched to identify biopsies with oxalate deposits, determine
      the density of oxalate deposits in renal graft biopsies, compare graft histology
      and function between allograft recipients with oxalate in the graft biopsies, and
      a control group of recipients without oxalate in the graft. RESULTS: Oxalate
      crystal deposits were observed in 61 of 5160 biopsies of native kidneys, and in
      76 of 1621 renal allograft biopsies, with a frequency of 1 and 4%, respectively.
      Sixty-three (9%) of 680 transplant recipients showed oxalate in graft biopsies
      obtained within the first year from transplantation, with 1.3 +/- 1.2 average
      number of oxalate deposits per mm(2) of biopsy tissue. The high oxalate density
      and decreased renal function were correlated in the first 2 years post-transplant
      (P = 0.037-0.05). Compared with a control group of 70 kidney graft recipients,
      the renal function was significantly lower in the oxalate group at 1 year, but
      not at 2 years post-transplant. High tubulo-interstitial scarring (P < 0.0001)
      was noted in repeated biopsies in the oxalate group, and was significantly
      greater than that in the control group (P = 0.027). No significant difference in
      graft loss was observed between oxalate and control groups, and although
      mortality was higher in the oxalate group, the difference was not significant.
      CONCLUSIONS: In summary, this study defines the frequency of oxalate deposition
      in native and allograft kidney biopsies, and suggests its possible negative
      impact on graft function beyond the early post-transplant period.

PMID- 19103738
TI  - Hypokalaemia: an independent risk factor of Enterobacteriaceae peritonitis in
      CAPD patients.
AB  - BACKGROUND: Hypokalaemia is a relatively common complication in uraemic patients
      undergoing continuous ambulatory peritoneal dialysis (CAPD). The hazards of
      hypokalaemia are multiple and have been correlated with patient morbidity and
      mortality. Whether it is associated with increased risk of peritonitis remains to
      be addressed. METHODS: We retrospectively analysed our CAPD patients who had
      complicating peritonitis in a 2-year period. The influence of hypokalaemia on the
      clinical features of peritonitis was assessed. From September 2003 to August
      2005, 140 unselected patients undergoing CAPD treatment and followed up in our
      hospital were recruited for the study. Hypokalaemia was defined as a serum
      potassium level <3.5 mmol/l. The impact of hypokalaemia on several clinical
      parameters, including the nutrition status, dialysis adequacy, occurrence of
      peritonitis and the etiologic pathogens, was analysed. RESULTS: During the study
      period, 462 determinations (23.6%) were below quantity <mmol/l. The overall
      peritonitis rate was 30.6 patient-month per episode (total 64 episodes). The
      prevalence of peritonitis was significantly higher in patients with hypokalaemia
      (6.9%) compared to those without hypokalaemia (2.1%, P < 0.001). Hypokalaemia was
      also associated with lower serum albumin (P < 0.001), serum phosphate (P <
      0.001), total serum cholesterol (P = 0.049) and normalized protein nitrogen
      appearance (P < 0.001). There was no correlation between serum potassium level
      and daily PD exchange volume, total Kt/V, urine volume or daily ultrafiltration
      volume. The peritoneal equilibration test was not significantly different between
      patients with and without hypokalaemia. When the aetiologic organisms of
      peritonitis were grouped according to their usual site of colonization,
      Enterobacteriaceae appeared to be much more prevalent than epidermal
      microorganisms (53.1% versus 18.8%, P = 0.004) in the hypokalaemia group.
      However, this was not the case in patients with normal serum potassium.
      CONCLUSION: CAPD patients with hypokalaemia are associated with a higher
      prevalence of peritonitis and poor nutritional status. Enterobacteriaceae were
      the predominant organisms causing peritonitis in the group with hypokalaemia.
      This unique and novel finding implies the translocation of these organisms from
      intestinal mucosa into the peritoneal cavity. A pathogenic mechanism linking
      malnutrition and hypokalaemia is also proposed.

PMID- 19103739
TI  - Regression of parathyroid hyperplasia by calcimimetics--fact or illusion?

PMID- 19103740
TI  - Raf kinase inhibitory protein function is regulated via a flexible pocket and
      novel phosphorylation-dependent mechanism.
AB  - Raf kinase inhibitory protein (RKIP/PEBP1), a member of the
      phosphatidylethanolamine binding protein family that possesses a conserved ligand
      binding pocket, negatively regulates the mammalian mitogen-activated protein
      kinase (MAPK) signaling cascade. Mutation of a conserved site (P74L) within the
      pocket leads to a loss or switch in the function of yeast or plant RKIP
      homologues. However, the mechanism by which the pocket influences RKIP function
      is unknown. Here we show that the pocket integrates two regulatory signals,
      phosphorylation and ligand binding, to control RKIP inhibition of Raf-1. RKIP
      association with Raf-1 is prevented by RKIP phosphorylation at S153. The P74L
      mutation increases kinase interaction and RKIP phosphorylation, enhancing Raf
      1/MAPK signaling. Conversely, ligand binding to the RKIP pocket inhibits kinase
      interaction and RKIP phosphorylation by a noncompetitive mechanism. Additionally,
      ligand binding blocks RKIP association with Raf-1. Nuclear magnetic resonance
      studies reveal that the pocket is highly dynamic, rationalizing its capacity to
      interact with distinct partners and be involved in allosteric regulation. Our
      results show that RKIP uses a flexible pocket to integrate ligand binding- and
      phosphorylation-dependent interactions and to modulate the MAPK signaling
      pathway. This mechanism is an example of an emerging theme involving the
      regulation of signaling proteins and their interaction with effectors at the
      level of protein dynamics.

PMID- 19103741
TI  - The Ku80 carboxy terminus stimulates joining and artemis-mediated processing of
      DNA ends.
AB  - Repair of DNA double-strand breaks (DSBs) is predominantly mediated by
      nonhomologous end joining (NHEJ) in mammalian cells. NHEJ requires binding of the
      Ku70-Ku80 heterodimer (Ku70/80) to the DNA ends and subsequent recruitment of the
      DNA-dependent protein kinase catalytic subunit (DNA-PK(CS)) and the XRCC4/ligase
      IV complex. Activation of the DNA-PK(CS) serine/threonine kinase requires an
      interaction with Ku70/80 and is essential for NHEJ-mediated DSB repair. In
      contrast to previous models, we found that the carboxy terminus of Ku80 is not
      absolutely required for the recruitment and activation of DNA-PK(CS) at DSBs,
      although cells that harbored a carboxy-terminal deletion in the Ku80 gene were
      sensitive to ionizing radiation and showed reduced end-joining capacity. More
      detailed analysis of this repair defect showed that DNA-PK(CS)
      autophosphorylation at Thr2647 was diminished, while Ser2056 was phosphorylated
      to normal levels. This resulted in severely reduced levels of Artemis nuclease
      activity in vivo and in vitro. We therefore conclude that the Ku80 carboxy
      terminus is important to support DNA-PK(CS) autophosphorylation at specific
      sites, which facilitates DNA end processing by the Artemis endonuclease and the
      subsequent joining reaction.

PMID- 19103742
TI  - Unscheduled Akt-triggered activation of cyclin-dependent kinase 2 as a key
      effector mechanism of apoptin's anticancer toxicity.
AB  - Apoptin, a protein from the chicken anemia virus, has attracted attention because
      it specifically kills tumor cells while leaving normal cells unharmed. The reason
      for this tumor selectivity is unclear and depends on subcellular localization, as
      apoptin resides in the cytoplasm of normal cells but in the nuclei of transformed
      cells. It was shown that nuclear localization and tumor-specific killing
      crucially require apoptin's phosphorylation by an as yet unknown kinase. Here we
      elucidate the pathway of apoptin-induced apoptosis and show that it essentially
      depends on abnormal phosphatidylinositol 3-kinase (PI3-kinase)/Akt activation,
      resulting in the activation of the cyclin-dependent kinase CDK2. Inhibitors as
      well as dominant-negative mutants of PI3-kinase and Akt not only inhibited CDK2
      activation but also protected cells from apoptin-induced cell death. Akt
      activated CDK2 by direct phosphorylation as well as by the phosphorylation
      induced degradation of the inhibitor p27(Kip1). Importantly, we also identified
      CDK2 as the principal kinase that phosphorylates apoptin and is crucially
      required for apoptin-induced cell death. Immortalized CDK2-deficient fibroblasts
      and CDK2 knockdown cells were markedly protected against apoptin. Thus, our
      results not only decipher the pathway of apoptin-induced cell death but also
      provide mechanistic insights for the selective killing of tumor cells.

PMID- 19103743
TI  - Defective DNA ligation during short-patch single-strand break repair in ataxia
      oculomotor apraxia 1.
AB  - Ataxia oculomotor apraxia 1 (AOA1) results from mutations in aprataxin, a
      component of DNA strand break repair that removes AMP from 5' termini. Despite
      this, global rates of chromosomal strand break repair are normal in a variety of
      AOA1 and other aprataxin-defective cells. Here we show that short-patch single
      strand break repair (SSBR) in AOA1 cell extracts bypasses the point of aprataxin
      action at oxidative breaks and stalls at the final step of DNA ligation,
      resulting in the accumulation of adenylated DNA nicks. Strikingly, this defect
      results from insufficient levels of nonadenylated DNA ligase, and short-patch
      SSBR can be restored in AOA1 extracts, independently of aprataxin, by the
      addition of recombinant DNA ligase. Since adenylated nicks are substrates for
      long-patch SSBR, we reasoned that this pathway might in part explain the apparent
      absence of a chromosomal SSBR defect in aprataxin-defective cells. Indeed,
      whereas chemical inhibition of long-patch repair did not affect SSBR rates in
      wild-type mouse neural astrocytes, it uncovered a significant defect in Aptx(-/-)
      neural astrocytes. These data demonstrate that aprataxin participates in
      chromosomal SSBR in vivo and suggest that short-patch SSBR arrests in AOA1
      because of insufficient nonadenylated DNA ligase.

PMID- 19103744
TI  - Postrecruitment regulation of RNA polymerase II directs rapid signaling responses
      at the promoters of estrogen target genes.
AB  - Under classical models for signal-dependent transcription in eukaryotes, DNA
      binding activator proteins regulate the recruitment of RNA polymerase II (Pol II)
      to a set of target promoters. However, recent studies, as well as our results
      herein, show that Pol II is widely distributed (i.e., "preloaded") at the
      promoters of many genes prior to specific signaling events. How Pol II
      recruitment and Pol II preloading fit within a unified model of gene regulation
      is unclear. In addition, the mechanisms through which cellular signals activate
      preloaded Pol II across mammalian genomes remain largely unknown. We show here
      that the predominant genomic outcome of estrogen signaling is the postrecruitment
      regulation of Pol II activity at target gene promoters, likely through specific
      changes in Pol II phosphorylation rather than through recruitment of Pol II to
      the promoters. Furthermore, we show that negative elongation factor binds to
      estrogen target promoters in conjunction with preloaded Pol II and represses gene
      expression until the appropriate signal is received. Finally, our studies reveal
      that the estrogen-dependent activation of preloaded Pol II facilitates rapid gene
      regulatory responses which play important physiological roles in regulating
      estrogen signaling itself. Our results reveal a broad use of postrecruitment Pol
      II regulation by the estrogen signaling pathway, a mode of regulation that is
      likely to apply to a wide variety of signal-regulated pathways.

PMID- 19103745
TI  - Regulation of SMN protein stability.
AB  - Spinal muscular atrophy (SMA) is caused by mutations of the survival of motor
      neuron (SMN1) gene and deficiency of full-length SMN protein (FL-SMN). All SMA
      patients retain one or more copies of the SMN2 gene, but the principal protein
      product of SMN2 lacks exon 7 (SMNDelta7) and is unable to compensate for a
      deficiency of FL-SMN. SMN is known to oligomerize and form a multimeric protein
      complex; however, the mechanisms regulating stability and degradation of FL-SMN
      and SMNDelta7 proteins have been largely unexplored. Using pulse-chase analysis,
      we characterized SMN protein turnover and confirmed that SMN was ubiquitinated
      and degraded by the ubiquitin proteasome system (UPS). The SMNDelta7 protein had
      a twofold shorter half-life than FL-SMN in cells despite similar intrinsic rates
      of turnover by the UPS in a cell-free assay. Mutations that inhibited SMN
      oligomerization and complex formation reduced the FL-SMN half-life. Furthermore,
      recruitment of SMN into large macromolecular complexes as well as increased
      association with several Gemin proteins was regulated in part by protein kinase
      A. Together, our data indicate that SMN protein stability is modulated by complex
      formation. Promotion of the SMN complex formation may be an important novel
      therapeutic strategy for SMA.

PMID- 19103746
TI  - A role for DNA polymerase mu in the emerging DJH rearrangements of the
      postgastrulation mouse embryo.
AB  - The molecular complexes involved in the nonhomologous end-joining process that
      resolves recombination-activating gene (RAG)-induced double-strand breaks and
      results in V(D)J gene rearrangements vary during mammalian ontogeny. In the
      mouse, the first immunoglobulin gene rearrangements emerge during midgestation
      periods, but their repertoires have not been analyzed in detail. We decided to
      study the postgastrulation DJ(H) joints and compare them with those present in
      later life. The embryo DJ(H) joints differed from those observed in perinatal
      life by the presence of short stretches of nontemplated (N) nucleotides. Whereas
      most adult N nucleotides are introduced by terminal deoxynucleotidyl transferase
      (TdT), the embryo N nucleotides were due to the activity of the homologous DNA
      polymerase mu (Polmu), which was widely expressed in the early ontogeny, as shown
      by analysis of Polmu(-/-) embryos. Based on its DNA-dependent polymerization
      ability, which TdT lacks, Polmu also filled in small sequence gaps at the coding
      ends and contributed to the ligation of highly processed ends, frequently found
      in the embryo, by pairing to internal microhomology sites. These findings show
      that Polmu participates in the repair of early-embryo, RAG-induced double-strand
      breaks and subsequently may contribute to preserve the genomic stability and
      cellular homeostasis of lymphohematopoietic precursors during development.

PMID- 19103747
TI  - SIRT1 exerts anti-inflammatory effects and improves insulin sensitivity in
      adipocytes.
AB  - SIRT1 is a prominent member of a family of NAD(+)-dependent enzymes and affects a
      variety of cellular functions ranging from gene silencing, regulation of the cell
      cycle and apoptosis, to energy homeostasis. In mature adipocytes, SIRT1 triggers
      lipolysis and loss of fat content. However, the potential effects of SIRT1 on
      insulin signaling pathways are poorly understood. To assess this, we used RNA
      interference to knock down SIRT1 in 3T3-L1 adipocytes. SIRT1 depletion inhibited
      insulin-stimulated glucose uptake and GLUT4 translocation. This was accompanied
      by increased phosphorylation of JNK and serine phosphorylation of insulin
      receptor substrate 1 (IRS-1), along with inhibition of insulin signaling steps,
      such as tyrosine phosphorylation of IRS-1, and phosphorylation of Akt and ERK. In
      contrast, treatment of cells with specific small molecule SIRT1 activators led to
      an increase in glucose uptake and insulin signaling as well as a decrease in
      serine phosphorylation of IRS-1. Moreover, gene expression profiles showed that
      SIRT1 expression was inversely related to inflammatory gene expression. Finally,
      we show that treatment of 3T3-L1 adipocytes with a SIRT1 activator attenuated
      tumor necrosis factor alpha-induced insulin resistance. Taken together, these
      data indicate that SIRT1 is a positive regulator of insulin signaling at least
      partially through the anti-inflammatory actions in 3T3-L1 adipocytes.

PMID- 19103748
TI  - Prep1 directly regulates the intrinsic apoptotic pathway by controlling Bcl-XL
      levels.
AB  - The Prep1 homeodomain transcription factor is essential in embryonic development.
      Prep1 hypomorphic mutant mouse (Prep1(i/i)) embryos (embryonic day 9.5) display
      an increased terminal deoxynucleotidyltransferase-mediated dUTP-biotin nick end
      labeling reaction compared to wild-type (WT) littermates. Prep1(i/i) mouse embryo
      fibroblasts (MEFs) show an increased basal level of annexin V binding activity,
      reduction of the mitochondrial-membrane potential, and increased caspase 9 and 3
      activation, indicating increased apoptosis. Prep1(i/i) MEFs also respond faster
      than WT MEFs to genotoxic stress, indicating increased activation of the
      intrinsic apoptotic pathways. We did not observe an increase in p53 or an
      abnormal p53 response to apoptotic stimuli. However, hypomorphic MEFs have
      decreased endogenous levels of antiapoptotic Bcl-X(L) mRNA and protein, and Bcl-x
      overexpression rescues the defect of Prep1(i/i) MEFs. Using transient
      transfections and chromatin immunoprecipitation, we identified the Bcl-x promoter
      as a novel target of Prep1. Thus, Prep1 directly controls mitochondrial
      homeostasis (and the apoptotic potential) by modulating Bcl-x gene expression.

PMID- 19103749
TI  - Brd4 coactivates transcriptional activation of NF-kappaB via specific binding to
      acetylated RelA.
AB  - Acetylation of the RelA subunit of NF-kappaB, especially at lysine-310, is
      critical for the transcriptional activation of NF-kappaB and the expression of
      inflammatory genes. In this study, we demonstrate that bromodomains of Brd4 bind
      to acetylated lysine-310. Brd4 enhances transcriptional activation of NF-kappaB
      and the expression of a subset of NF-kappaB-responsive inflammatory genes in an
      acetylated lysine-310-dependent manner. Bromodomains of Brd4 and acetylated
      lysine-310 of RelA are both required for the mutual interaction and coactivation
      function of Brd4. Finally, we demonstrate that Brd4 further recruits CDK9 to
      phosphorylate C-terminal domain of RNA polymerase II and facilitate the
      transcription of NF-kappaB-dependent inflammatory genes. Our results identify
      Brd4 as a novel coactivator of NF-kappaB through specifically binding to
      acetylated lysine-310 of RelA. In addition, these studies reveal a mechanism by
      which acetylated RelA stimulates the transcriptional activity of NF-kappaB and
      the NF-kappaB-dependent inflammatory response.

PMID- 19103750
TI  - The neurofibromatosis 2 protein, merlin, regulates glial cell growth in an ErbB2-
      and Src-dependent manner.
AB  - Individuals with the inherited cancer predisposition syndrome neurofibromatosis 2
      (NF2) develop several central nervous system (CNS) malignancies, including glial
      cell neoplasms (ependymomas). Recent studies have suggested that the NF2 protein,
      merlin (or schwannomin), may regulate receptor tyrosine kinase signaling,
      intracellular mitogenic growth control pathways, or adherens junction
      organization in non-nervous-system cell types. For this report, we used glial
      fibrillary acidic protein conditional knockout mice and derivative glia to
      determine how merlin regulates CNS glial cell proliferation. We show that the
      loss of merlin in glial cells results in increased proliferation in vitro and in
      vivo. Merlin regulation of glial cell growth reflects deregulated Src activity,
      such that pharmacologic or genetic inhibition of Src activation reduces Nf2(-/-)
      glial cell growth to wild-type levels. We further show that Src regulates Nf2(-/
      ) glial cell growth by sequentially regulating FAK and paxillin
      phosphorylation/activity. Next, we demonstrate that Src activation results from
      merlin regulation of ErbB2 activation and that genetic or pharmacologic ErbB2
      inhibition reduces Nf2(-/-) glial cell Src/Src effector activation and
      proliferation to wild-type levels. Lastly, we show that merlin competes with Src
      for direct binding to ErbB2 and present a novel molecular mechanism for merlin
      regulation of ErbB2-dependent Src signaling and growth control.

PMID- 19103751
TI  - Differential contribution of the Gata1 gene hematopoietic enhancer to erythroid
      differentiation.
AB  - GATA1 is a key regulator of erythroid cell differentiation. To examine how Gata1
      gene expression is regulated in a stage-specific manner, transgenic mouse lines
      expressing green fluorescent protein (GFP) reporter from the Gata1 locus in a
      bacterial artificial chromosome (G1BAC-GFP) were prepared. We found that the GFP
      reporter expression faithfully recapitulated Gata1 gene expression. Using GFP
      fluorescence in combination with hematopoietic surface markers, we established a
      purification protocol for two erythroid progenitor fractions, referred to as
      burst-forming units-erythroid cell-related erythroid progenitor (BREP) and CFU
      erythroid cell-related erythroid progenitor (CREP) fractions. We examined the
      functions of the Gata1 gene hematopoietic enhancer (G1HE) and the highly
      conserved GATA box in the enhancer core. Both deletion of the G1HE and
      substitution mutation of the GATA box caused almost complete loss of GFP
      expression in the BREP fraction, but the CREP stage expression was suppressed
      only partially, indicating the critical contribution of the GATA box to the BREP
      stage expression of Gata1. Consistently, targeted deletion of G1HE from the
      chromosomal Gata1 locus provoked suppressed expression of the Gata1 gene in the
      BREP fraction, which led to aberrant accumulation of BREP stage hematopoietic
      progenitor cells. These results demonstrate the physiological significance of the
      dynamic regulation of Gata1 gene expression in a differentiation stage-specific
      manner.

PMID- 19103753
TI  - Activation of Stat3 by heregulin/ErbB-2 through the co-option of progesterone
      receptor signaling drives breast cancer growth.
AB  - Cross talk between the steroid hormone receptors for estrogen and progesterone
      (PR) and the ErbB family of receptor tyrosine kinases appears to be a hallmark of
      breast cancer growth, but its underlying mechanism remains poorly explored. Here
      we have highlighted signal transducer and activator of transcription 3 (Stat3) as
      a key protein activated by heregulin (HRG), a ligand of the ErbB receptors,
      through co-opted, ligand-independent PR function as a signaling molecule. Stat3
      activation was an absolute requirement in HRG-induced mammary tumor growth, and
      targeting Stat3 effectively inhibited growth of breast cancer cells with
      activated HRG/ErbB-2 and PR. Our findings unravel a novel potential therapeutic
      intervention in PR- and ErbB-2-positive breast tumors, involving the specific
      blockage of PR signaling activity.

PMID- 19103754
TI  - The C-terminal domain of Cernunnos/XLF is dispensable for DNA repair in vivo.
AB  - The core nonhomologous end-joining DNA repair pathway is composed of seven
      factors: Ku70, Ku80, DNA-PKcs, Artemis, XRCC4 (X4), DNA ligase IV (L4), and
      Cernunnos/XLF (Cernunnos). Although Cernunnos and X4 are structurally related and
      participate in the same complex together with L4, they have distinct functions
      during DNA repair. L4 relies on X4 but not on Cernunnos for its stability, and L4
      is required for optimal interaction of Cernunnos with X4. We demonstrate here,
      using in vitro-generated Cernunnos mutants and a series of functional assays in
      vivo, that the C-terminal region of Cernunnos is dispensable for its activity
      during DNA repair.

PMID- 19103752
TI  - Inhibition of microtubule assembly in osteoblasts stimulates bone morphogenetic
      protein 2 expression and bone formation through transcription factor Gli2.
AB  - Bone morphogenetic protein 2 (BMP-2) is essential for postnatal bone formation
      and fracture repair. By screening chemical libraries for BMP-2 mimics using a
      cell-based assay, we identified inhibitors of microtubule assembly as stimulators
      of BMP-2 transcription. These microtubule inhibitors increased osteoblast
      differentiation in vitro, stimulated periosteal bone formation when injected
      locally over murine calvaria, and enhanced trabecular bone formation when
      administered systemically in vivo. To explore molecular mechanisms mediating
      these responses, we examined effects of microtubule inhibitors on the hedgehog
      (Hh) pathway, since this pathway is known to regulate BMP-2 transcription in
      osteoblasts and microtubules have been shown to be involved in Hh signaling in
      Drosophila. Here we show that in osteoblasts, inhibition of microtubule assembly
      increased cytoplasmic levels and transcriptional activity of Gli2, a
      transcriptional mediator of Hh signaling that we have previously shown to enhance
      BMP-2 expression in osteoblasts (M. Zhao et al., Mol. Cell. Biol. 26:6197-6208,
      2006). Microtubule inhibition blocked beta-TrCP-mediated proteasomal processing
      of Gli2 in osteoblasts. In summary, inhibition of microtubule assembly enhances
      BMP-2 gene transcription and subsequent bone formation, in part, through
      inhibiting proteasomal processing of Gli2 and increasing intracellular Gli2
      concentrations.

PMID- 19103755
TI  - The double-histone-acetyltransferase complex ATAC is essential for mammalian
      development.
AB  - Acetylation of the histone tails, catalyzed by histone acetyltransferases (HATs),
      is a well-studied process that contributes to transcriptionally active chromatin
      states. Here we report the characterization of a novel mammalian HAT complex,
      which contains the two acetyltransferases GCN5 and ATAC2 as well as other
      proteins linked to chromatin metabolism. This multisubunit complex has a similar
      but distinct subunit composition to that of the Drosophila ADA2A-containing
      complex (ATAC). Recombinant ATAC2 has a weak HAT activity directed to histone H4.
      Moreover, depletion of ATAC2 results in the disassembly of the complex,
      indicating that ATAC2 not only carries out an enzymatic function but also plays
      an architectural role in the stability of mammalian ATAC. By targeted disruption
      of the Atac2 locus in mice, we demonstrate for the first time the essential role
      of the ATAC complex in mammalian development, histone acetylation, cell cycle
      progression, and prevention of apoptosis during embryogenesis.

PMID- 19103756
TI  - Plk3 interacts with and specifically phosphorylates VRK1 in Ser342, a downstream
      target in a pathway that induces Golgi fragmentation.
AB  - Golgi fragmentation is a process that is necessary to allow its redistribution
      into daughter cells during mitosis, a process controlled by serine-threonine
      kinases. This Golgi fragmentation is activated by MEK1 and Plk3. Plk3 is a kinase
      that is a downstream target in the Golgi fragmentation pathway induced by MEK1 or
      by nocodazole. In this work, we have identified that Plk3 and VRK1 are two
      consecutive steps in this signaling pathway. Plk3 interacts with VRK1, forming a
      stable complex detected by reciprocal immunoprecipitations and pull-down assays;
      VRK1 colocalizes with giantin in the Golgi apparatus, as Plk3 also does, forming
      clearly detectable granules. VRK1 does not phosphorylate Plk3, but Plk3
      phosphorylates the C-terminal region of VRK1 in Ser342. VRK1 with substitutions
      in S342 is catalytically active but blocks Golgi fragmentation, indicating that
      its specific phosphorylation is necessary for this process. The induction of
      Golgi fragmentation by MEK1 and Plk3 can be inhibited by kinase-dead VRK1, the
      knockdown of VRK1 by siVRK1, kinase-dead Plk3, or PD98059, a MEK1 inhibitor. The
      Plk3-VRK1 kinase module might represent two consecutive steps of a signaling
      cascade that participates in the regulation of Golgi fragmentation.

PMID- 19103757
TI  - Trypanosoma brucei spliced leader RNA maturation by the cap 1 2'-O-ribose
      methyltransferase and SLA1 H/ACA snoRNA pseudouridine synthase complex.
AB  - Kinetoplastid flagellates attach a 39-nucleotide spliced leader (SL) upstream of
      protein-coding regions in polycistronic RNA precursors through trans splicing. SL
      modifications include cap 2'-O-ribose methylation of the first four nucleotides
      and pseudouridine (psi) formation at uracil 28. In Trypanosoma brucei, TbMTr1
      performs 2'-O-ribose methylation of the first transcribed nucleotide, or cap 1.
      We report the characterization of an SL RNA processing complex with TbMTr1 and
      the SLA1 H/ACA small nucleolar ribonucleoprotein (snoRNP) particle that guides SL
      psi(28) formation. TbMTr1 is in a high-molecular-weight complex containing the
      four conserved core proteins of H/ACA snoRNPs, a kinetoplastid-specific protein
      designated methyltransferase-associated protein (TbMTAP), and the SLA1 snoRNA.
      TbMTAP-null lines are viable but have decreased SL RNA processing efficiency in
      cap methylation, 3'-end maturation, and psi(28) formation. TbMTAP is required for
      association between TbMTr1 and the SLA1 snoRNP but does not affect U1 small
      nuclear RNA methylation. A complex methylation profile in the mRNA population of
      TbMTAP-null lines indicates an additional effect on cap 4 methylations. The
      TbMTr1 complex specializes the SLA1 H/ACA snoRNP for efficient processing of
      multiple modifications on the SL RNA substrate.

PMID- 19103758
TI  - PTEN loss promotes mitochondrially dependent type II Fas-induced apoptosis via
      PEA-15.
AB  - Two distinct biochemical signals are delivered by the CD95/Fas death receptor.
      The molecular basis for the differential mitochondrially independent (type I) and
      mitochondrially dependent (type II) Fas apoptosis pathways is unknown. By
      analyzing 24 Fas-sensitive tumor lines, we now demonstrate that
      expression/activity of the PTEN tumor suppressor strongly correlates with the
      distinct Fas signals. PTEN loss-of-function and gain-of-function studies
      demonstrate the ability to interconvert between type I and type II Fas pathways.
      Importantly, from analyses of Bcl-2 transgenic Pten(+/-) mice, Pten
      haploinsufficiency converts Fas-induced apoptosis from a Bcl-2-independent to a
      Bcl-2-sensitive response in primary thymocytes and activated T lymphocytes. We
      further show that PTEN influences Fas signaling, at least in part, by regulating
      PEA-15 phosphorylation and activity that, in turn, regulate the ability of Bcl-2
      to suppress Fas-induced apoptosis. Thus, PTEN is a key molecular rheostat that
      determines whether a cell dies by a mitochondrially independent type I versus a
      mitochondrially dependent type II apoptotic pathway upon Fas stimulation.

PMID- 19103759
TI  - Acetylation-dependent interaction of SATB1 and CtBP1 mediates transcriptional
      repression by SATB1.
AB  - Special AT-rich binding protein 1 (SATB1) acts as a global regulator of gene
      expression by recruiting various corepressor or coactivator complexes, thereby
      establishing a unique chromatin structure at its genomic targets in a context
      dependent manner. Although SATB1 acts predominantly as a repressor via
      recruitment of histone deacetylase 1 (HDAC1) complexes, the precise mechanism of
      global repression is not clear. Here we report that SATB1 and C-terminal binding
      protein 1 (CtBP1) form a repressor complex in vivo. The interaction occurs via
      the CtBP1 interaction consensus motif PVPLS within the PDZ-like domain of SATB1.
      The acetylation of SATB1 upon LiCl and ionomycin treatments disrupts its
      association with CtBP1, resulting in enhanced target gene expression. Chromatin
      immunoprecipitation analysis indicated that the occupancy of CtBP1 and HDAC1 is
      gradually decreased and the occupancy of PCAF is elevated at the SATB1 binding
      sites within the human interleukin-2 and mouse c-Myc promoters. Moreover, gene
      expression profiling studies using cells in which expression of SATB1 and CtBP1
      was silenced indicated commonly targeted genes that may be coordinately repressed
      by the SATB1-CtBP1 complex. Collectively, these results provide a mechanistic
      insight into the role of SATB1-CtBP1 interaction in the repression and
      derepression of SATB1 target genes during Wnt signaling in T cells.

PMID- 19103761
TI  - Heterocyclic thioureylenes protect from calcium-dependent neuronal cell death.
AB  - Calcium-dependent cell death occurs in neurodegenerative diseases and ischemic or
      traumatic brain injury. We analyzed whether thioureylenes can act in a
      neuroprotective manner by pharmacological suppression of calcium-dependent
      pathological pathways. In human neuroblastoma (SK-N-SH) cells, thioureylenes
      (thiopental, carbimazole) inhibited the calcium-dependent neuronal protein
      phosphatase (PP)-2B, the activation of the proapoptotic transcription factor
      nuclear factor of activated T-cells, BAD-induced initiation of caspase-3, and
      poly-(ADP-ribose)-polymerase cleavage. Caspase-3-independent cell death was
      attenuated by carbimazole and the protein kinase C (PKC) delta inhibitor
      rottlerin by a PP-2B-independent mechanism. Neuroprotective effects were mediated
      by the redox-active sulfur of thioureylenes. Furthermore, we observed that the
      route of calcium mobilization was differentially linked to caspase-dependent or
      independent cell death and that BAD dephosphorylation did not necessarily induce
      intrinsic caspase activation. In addition, a new 30- to 35-kDa caspase-3 fragment
      with an unknown function was identified. In organotypic hippocampal slice
      cultures, thioureylenes inhibited caspase-3 activation or reduced N-methyl-d
      aspartate and kainic acid receptor-mediated cell death that was independent of
      caspase-3. Because prolonged inhibition of caspase-3 resulted in caspase
      independent cellular damage, different types of cell death must be taken under
      therapeutic consideration. Here we show that thioureylenes in combination with
      PKCdelta inhibitors might represent a promising therapeutic approach to attenuate
      neuronal damage.

PMID- 19103760
TI  - Butein suppresses constitutive and inducible signal transducer and activator of
      transcription (STAT) 3 activation and STAT3-regulated gene products through the
      induction of a protein tyrosine phosphatase SHP-1.
AB  - The aim of the current study is to determine whether butein (3,4,2',4'
      tetrahydroxychalcone) exhibits antiproliferative effects against tumor cells
      through suppression of the signal transducer and activator of transcription 3
      (STAT3) activation pathway. We investigated the effects of butein on constitutive
      and inducible STAT3 activation, role of tyrosine kinases and phosphatases in
      STAT3 activation, STAT3-regulated gene products, and growth modulation of tumor
      cells. We found that this chalcone inhibited both constitutive and interleukin-6
      inducible STAT3 activation in multiple myeloma (MM) cells. The suppression was
      mediated through the inhibition of activation of the upstream kinases c-Src,
      Janus-like kinase (JAK) 1, and JAK2. Vanadate treatment reversed the butein
      induced down-regulation of STAT3 activation, suggesting the involvement of a
      tyrosine phosphatase. Indeed, we found that butein induced the expression of the
      tyrosine phosphatase SHP-1 and deletion of SHP-1 gene by small interfering RNA
      abolished the ability of butein to inhibit STAT3 activation, suggesting the
      critical role of SHP-1 in the action of this chalcone. Butein down-regulated the
      expression of STAT3-regulated gene products such as Bcl-xL, Bcl-2, cyclin D1, and
      Mcl-1, and this led to the suppression of proliferation and induction of
      apoptosis. Consistent with these results, overexpression of constitutive active
      STAT3 significantly reduced the butein-induced apoptosis. Moreover, we found that
      butein significantly potentiated the apoptotic effects of thalidomide and Velcade
      in MM cells. Overall, these results suggest that butein is a novel blocker of
      STAT3 activation and thus may have potential in suppression of tumor cell
      proliferation and reversal of chemoresistance in MM cells.

PMID- 19103762
TI  - Mycoplasma genitalium-encoded MG309 activates NF-kappaB via Toll-like receptors 2
      and 6 to elicit proinflammatory cytokine secretion from human genital epithelial
      cells.
AB  - Mycoplasma genitalium has been implicated in several important reproductive tract
      syndromes in women, including pelvic inflammatory disease, cervicitis, and tubal
      factor infertility. The mechanisms of immune activation are unclear, and we
      sought to determine whether M. genitalium was capable of activating innate immune
      responses through ligation of highly expressed Toll-like receptors (TLR) of the
      genital tract. Using HEK293 cells expressing specific human TLR, viable M.
      genitalium and the recombinant C-terminal portion of the immunogenic protein
      MG309 (rMG309c) were shown to activate NF-kappaB via TLR2/6. These data provided
      a putative mechanism for activation of the innate response in genital tissues.
      Genital epithelial cells (EC) are the first responders to sexually transmitted
      pathogens and express high levels of TLR2 and -6. Following exposure to purified
      rMG309c, vaginal and ecto- and endocervical EC secreted proinflammatory
      cytokines, including interleukin-6 (IL-6) and IL-8. Vaginal EC were less
      responsive than cervical EC. The capacity of rMG309c to bind TLR2/6 and elicit
      inflammation was sensitive to proteinase K digestion and independent of
      traditional N-terminal lipoylation. Furthermore, the immunostimulatory capacity
      of rMG309c was localized specifically to a 91-amino-acid subfragment of the
      recombinant protein, suggesting that TLR activation is likely amino acid based.
      Together, these data indicated that human vaginal and cervical EC are
      immunologically responsive to M. genitalium and to purified rMG309c via highly
      expressed TLR of the genital tract. These findings provide valuable insights into
      the mechanisms for activation of acute-phase inflammatory responses and suggest
      that M. genitalium colonization of reproductive tract tissues may result in
      inflammatory sequelae.

PMID- 19103763
TI  - Major surface protein LipL32 is not required for either acute or chronic
      infection with Leptospira interrogans.
AB  - Leptospira interrogans is responsible for leptospirosis, a zoonosis of worldwide
      distribution. LipL32 is the major outer membrane protein of pathogenic
      leptospires, accounting for up to 75% of total outer membrane protein. In recent
      times LipL32 has become the focus of intense study because of its surface
      location, dominance in the host immune response, and conservation among
      pathogenic species. In this study, an lipL32 mutant was constructed in L.
      interrogans using transposon mutagenesis. The lipL32 mutant had normal morphology
      and growth rate compared to the wild type and was equally adherent to
      extracellular matrix. Protein composition of the cell membranes was found to be
      largely unaffected by the loss of LipL32, with no obvious compensatory increase
      in other proteins. Microarray studies found no obvious stress response or
      upregulation of genes that may compensate for the loss of LipL32 but did suggest
      an association between LipL32 and the synthesis of heme and vitamin B(12). When
      hamsters were inoculated by systemic and mucosal routes, the mutant caused acute
      severe disease manifestations that were indistinguishable from wild-type L.
      interrogans infection. In the rat model of chronic infection, the LipL32 mutant
      colonized the renal tubules as efficiently as the wild-type strain. In
      conclusion, this study showed that LipL32 does not play a role in either the
      acute or chronic models of infection. Considering the abundance and conservation
      of LipL32 among all pathogenic Leptospira spp. and its absence in saprophytic
      Leptospira, this finding is remarkable. The role of this protein in leptospiral
      biology and pathogenesis thus remains elusive.

PMID- 19103764
TI  - Roles of the extraintestinal pathogenic Escherichia coli ZnuACB and ZupT zinc
      transporters during urinary tract infection.
AB  - Roles of the ZnuACB and ZupT transporters were assessed in Escherichia coli K-12
      and uropathogenic E. coli (UPEC) CFT073. K-12 and CFT073 Deltaznu DeltazupT
      mutants demonstrated decreased (65)Zn(2+) uptake and growth in minimal medium.
      CFT073Deltaznu demonstrated an intermediate decrease of (65)Zn(2+) uptake and
      growth in minimal medium, whereas the CFT073DeltazupT mutant grew as well as
      CFT073 and exhibited a less marked decrease in (65)Zn(2+) uptake. CFT073 mutants
      grew as well as the wild type in human urine. In competitive infections in CBA/J
      mice, the DeltazupT mutant demonstrated no disadvantage during urinary tract
      infection. In contrast, the UPEC Deltaznu and Deltaznu DeltazupT strains
      demonstrated significantly reduced numbers in the bladders (mean 4.4- and 30-fold
      reductions, respectively) and kidneys (mean 41- and 48-fold reductions,
      respectively). In addition, in single-strain infection experiments, the Deltaznu
      and Deltaznu DeltazupT mutants were reduced in the kidneys (P = 0.0012 and P <
      0.0001, respectively). Complementation of the CFT073 Deltaznu DeltazupT mutant
      with the znuACB genes restored growth in Zn-deficient medium and bacterial
      numbers in the bladder and kidneys. The loss of the zinc transport systems
      decreased both motility and resistance to hydrogen peroxide, which could be
      restored by supplementation with zinc. Overall, the results indicate that Znu and
      ZupT are required for growth in zinc limited-conditions, that Znu is the
      predominant zinc transporter, and that the loss of Znu and ZupT has a cumulative
      effect on fitness during UTI, which may in part be due to reduced resistance to
      oxidative stress and motility.

PMID- 19103765
TI  - Role of neutrophils in response to Bordetella pertussis infection in mice.
AB  - Pertussis is an acute respiratory disease caused by the bacterium Bordetella
      pertussis, for which humans are the only known reservoir. During infection, B.
      pertussis releases several toxins, including pertussis toxin (PT) and adenylate
      cyclase toxin (ACT), which have both been shown to play roles in promoting
      bacterial growth during early infection in a mouse model. Furthermore, in vitro
      and in vivo studies suggest that PT and ACT affect neutrophil chemotaxis and/or
      function, thereby altering the innate immune response. In this study we depleted
      animals of neutrophils to investigate whether neutrophils play a protective role
      during B. pertussis infection in mice. In addition, by infection with toxin
      deficient strains, we investigated whether neutrophils are the main targets for
      PT and/or ACT activity in promoting bacterial growth. Surprisingly, we found no
      role for neutrophils during B. pertussis infection in naive mice. However, in
      previously infected (immune) mice or in mice receiving immune serum, we observed
      a significant role for neutrophils during infection. Furthermore, in this immune
      mouse model our evidence indicates that neutrophils appear to be the main target
      cells for ACT, but not for PT.

PMID- 19103767
TI  - Role of the dosR-dosS two-component regulatory system in Mycobacterium
      tuberculosis virulence in three animal models.
AB  - The Mycobacterium tuberculosis dosR gene (Rv3133c) is part of an operon, Rv3134c
      Rv3132c, and encodes a response regulator that has been shown to be upregulated
      by hypoxia and other in vitro stress conditions and may be important for
      bacterial survival within granulomatous lesions found in tuberculosis. DosR is
      activated in response to hypoxia and nitric oxide by DosS (Rv3132c) or DosT
      (Rv2027c). We compared the virulence levels of an M. tuberculosis dosR-dosS
      deletion mutant (DeltadosR-dosS [DeltadosR-S]), a dosR-complemented strain, and
      wild-type H37Rv in rabbits, guinea pigs, and mice infected by the aerosol route
      and in a mouse hollow-fiber model that may mimic in vivo granulomatous
      conditions. In the mouse and the guinea pig models, the DeltadosR-S mutant
      exhibited a growth defect. In the rabbit, the DeltadosR-S mutant did not
      replicate more than the wild type. In the hollow-fiber model, the mutant
      phenotype was not different from that of the wild-type strain. Our analyses
      reveal that the dosR and dosS genes are required for full virulence and that
      there may be differences in the patterns of attenuation of this mutant between
      the animal models studied.

PMID- 19103766
TI  - An engineered human antibody fab fragment specific for Pseudomonas aeruginosa
      PcrV antigen has potent antibacterial activity.
AB  - Pseudomonas aeruginosa is an opportunistic pathogen that can cause acute lung
      injury and mortality through the delivery of exotoxins by the type III secretion
      system (TTSS). PcrV is an important structural protein of the TTSS. An engineered
      human antibody Fab fragment that binds to the P. aeruginosa PcrV protein with
      high affinity has been identified and has potent in vitro neutralization activity
      against the TTSS. The instillation of a single dose of Fab into the lungs of mice
      provided protection against lethal pulmonary challenge of P. aeruginosa and led
      to a substantial reduction of viable bacterial counts in the lungs. These results
      demonstrate that blocking of the TTSS by a Fab lacking antibody Fc-mediated
      effector functions can be sufficient for the effective clearance of pulmonary P.
      aeruginosa infection.

PMID- 19103768
TI  - Salmonella-containing vacuoles display centrifugal movement associated with cell
      to-cell transfer in epithelial cells.
AB  - Intracellular Salmonella enterica serovar Typhimurium (serovar Typhimurium)
      occupies a Salmonella-containing vacuole (SCV) where bacterial effector proteins
      are secreted into the host cell using type III secretion systems (T3SS).
      Cytoskeletal motor proteins and T3SS-delivered effector proteins facilitate SCV
      positioning to juxtanuclear positions where bacterial replication occurs. Here,
      we show that this characteristic SCV positioning is not maintained by all SCVs
      during infection of HeLa cells. Notably, juxtanuclear SCV localization that
      occurs by 8 to 14 h postinfection is followed by significant centrifugal
      displacement of a subset of SCVs toward the host cell periphery by 24 h
      postinfection. This novel phenotype requires bacterial protein synthesis, a
      functional Salmonella pathogenicity island 2 (SPI-2)-encoded T3SS, intact
      microtubules, and kinesin-1 motor protein. Bacteria lacking PipB2, a kinesin
      recruiting T3SS effector, did not exhibit centrifugal displacement and remained
      at juxtanuclear positions throughout 24 h of infection. While levels of the SPI-2
      effectors PipB2 and SifA increased during 24 h postinfection, a corresponding
      decrease in levels of the SPI-1 T3SS effectors SipA and SopB, both known to
      mediate juxtanuclear SCV positioning, was observed. A fluorescence-based assay
      indicated that wild-type serovar Typhimurium transferred from infected to
      uninfected epithelial cells while strains deficient in SPI-2 T3SS secretion or
      PipB2 did not. Our results reveal a novel SCV phenotype implicated in the cell-to
      cell spread of serovar Typhimurium during infection.

PMID- 19103769
TI  - The Yersinia pestis caf1M1A1 fimbrial capsule operon promotes transmission by
      flea bite in a mouse model of bubonic plague.
AB  - Plague is a zoonosis transmitted by fleas and caused by the gram-negative
      bacterium Yersinia pestis. During infection, the plasmidic caf1M1A1 operon that
      encodes the Y. pestis F1 protein capsule is highly expressed, and anti-F1
      antibodies are protective. Surprisingly, the capsule is not required for
      virulence after injection of cultured bacteria, even though it is an
      antiphagocytic factor and capsule-deficient Y. pestis strains are rarely
      isolated. We found that a caf-negative Y. pestis mutant was not impaired in
      either flea colonization or virulence in mice after intradermal inoculation of
      cultured bacteria. In contrast, absence of the caf operon decreased bubonic
      plague incidence after a flea bite. Successful development of plague in mice
      infected by flea bite with the caf-negative mutant required a higher number of
      infective bites per challenge. In addition, the mutant displayed a highly
      autoaggregative phenotype in infected liver and spleen. The results suggest that
      acquisition of the caf locus via horizontal transfer by an ancestral Y. pestis
      strain increased transmissibility and the potential for epidemic spread. In
      addition, our data support a model in which atypical caf-negative strains could
      emerge during climatic conditions that favor a high flea burden. Human infection
      with such strains would not be diagnosed by the standard clinical tests that
      detect F1 antibody or antigen, suggesting that more comprehensive surveillance
      for atypical Y. pestis strains in plague foci may be necessary. The results also
      highlight the importance of studying Y. pestis pathogenesis in the natural
      context of arthropod-borne transmission.

PMID- 19103770
TI  - Toll-like receptor 2 and NALP2 mediate induction of human beta-defensins by
      fusobacterium nucleatum in gingival epithelial cells.
AB  - We previously reported that infection by Fusobacterium nucleatum strongly induced
      the expression of both human beta-defensin 2 (HBD-2) and HBD-3 by gingival
      epithelial cells. The aim of this study was to characterize the pattern
      recognition receptors (PRRs) and regulatory mechanisms involved in the induction
      of HBD-2 and -3 expression by F. nucleatum in gingival epithelial cells.
      Immortalized human gingival epithelial HOK-16B cells were infected with live or
      heat-killed F. nucleatum, and the expression of HBDs and interleukin-8 (IL-8) was
      examined by real-time reverse transcription-PCR and enzyme-linked immunosorbent
      assay, respectively. Live, but not heat-killed, F. nucleatum invaded HOK-16B
      cells, as seen by confocal microscopy and flow cytometry. Live F. nucleatum
      induced both HBD-2 and -3 efficiently, whereas heat-killed bacteria induced only
      HBD-3 at a reduced level. Knockdown of NACHT-LRR- and pyrin domain-containing
      protein 2 (NALP2), the most abundant intracellular PRR in HOK-16B cells, by RNA
      interference (RNAi) significantly reduced the induction of HBD-3 but not HBD-2
      and IL-8. In addition, knockdown of Toll-like receptor 2 (TLR2) by RNAi reduced
      the upregulation of HBD-2 and -3 but not IL-8. Heat-killed F. nucleatum was
      hindered in its ability to activate TLR2 and JNK signaling pathways. Theses data
      show that TLR2 and NALP2 mediate the induction of HBDs by F. nucleatum in
      gingival epithelial cells, but thresholds for the two HBD genes are different.

PMID- 19103771
TI  - The H35A mutated alpha-toxin interferes with cytotoxicity of staphylococcal alpha
      toxin.
AB  - Staphylococcal alpha-toxin is an important virulence factor for Staphylococcus
      aureus to cause severe infections. In this study, we explored whether the toxoid
      of alpha-toxin may be utilized to block the toxicity of wild-type alpha-toxin. We
      created a series of H35A mutated alpha-toxin expression strains and revealed that
      the H35A mutation eliminates the activity of alpha-toxin using a human lung
      epithelial cell line (A549). More importantly, we found that either the
      pretreatment or simultaneous treatment of the epithelial cells with alpha-toxin
      H35A completely disrupted the cytotoxicity of alpha-toxin. Specifically, we
      demonstrated that alpha-toxin-H35A can effectively interfere with the pore
      formation and the internalization of alpha-toxin using cytotoxicity and
      immunofluorescence assays. In addition, we found that the removal of either the
      30-amino-acid (aa) or 99-aa C-terminal region of alpha-toxin-H35A reactivated its
      cytotoxicity, indicating that interactions between the alanine residue at
      position 35 and these C-terminal regions may be associated with interrupting the
      toxic activity of alpha-toxin-H35A. Taken together, these results suggest that
      the alpha-toxin-H35A protein may be developed as a potential alternative
      therapeutic agent for treating early stages of S. aureus infections.

PMID- 19103773
TI  - Role of melanin pigment in expression of Vibrio cholerae virulence factors.
AB  - We identified the mutated gene locus in a pigment-overproducing Vibrio cholerae
      mutant of strain A1552. The deduced gene product is suggested to be an
      oxidoreductase based on partial homology to putative homogentisate 1,2
      dioxygenase in Pseudomonas aeruginosa and Mesorhizobium loti, and we propose that
      the gene VC1345 in the V. cholerae genome be denoted hmgA in accordance with the
      nomenclature for other species. The hmgA::mini-Tn5 mutant showed a nonpigmented
      phenotype after complementation with a plasmid clone carrying the WT hmgA(+)
      locus. Microarray transcription analysis revealed that expression of hmgA and the
      neighboring genes encoding a postulated two-component sensor system was growth
      phase dependent. Results from quantitative reverse transcription-PCR analysis
      showed that hmgA operon expression was reduced in the rpoS mutant, but pigment
      production by the WT V. cholerae or the hmgA mutant was not detectably influenced
      by the stationary-phase regulator RpoS. The pigmented mutant showed increased UV
      resistance in comparison with the WT strain. Interestingly, the pigment-producing
      mutant expressed more toxin-coregulated pilus and cholera toxin than WT V.
      cholerae. Moreover, the hmgA mutant showed a fivefold increase in the ability to
      colonize the intestines of infant mice. A possible mechanism by which pigment
      production might cause induction of the ToxR regulon due to generation of
      hydrogen peroxide was supported by results from tests showing that externally
      supplied H(2)O(2) led to higher TcpA levels. Taken together, our findings suggest
      that melanin pigment formation may play a role in V. cholerae virulence factor
      expression.

PMID- 19103772
TI  - Defects in innate immunity predispose C57BL/6J-Leprdb/Leprdb mice to infection by
      Staphylococcus aureus.
AB  - Foot and ankle infections are the most common cause of hospitalization among
      diabetic patients, and Staphylococcus aureus is a major pathogen implicated in
      these infections. Patients with insulin-resistant (type 2) diabetes are more
      susceptible to bacterial infections than nondiabetic subjects, but the
      pathogenesis of these infections is poorly understood. C57BL/6J-Lepr(db)/Lepr(db)
      (hereafter, db/db) mice develop type 2 diabetes due to a recessive, autosomal
      mutation in the leptin receptor. We established a S. aureus hind paw infection in
      diabetic db/db and nondiabetic Lepr(+/+) (+/+) mice to investigate host factors
      that predispose diabetic mice to infection. Nondiabetic +/+ mice resolved the S.
      aureus hind paw infection within 10 days, whereas db/db mice with persistent
      hyperglycemia developed a chronic infection associated with a high bacterial
      burden. Diabetic db/db mice showed a more robust neutrophil infiltration to the
      infection site and higher levels of chemokines in the infected tissue than +/+
      mice. Blood from +/+ mice killed S. aureus in vitro, whereas db/db blood was
      defective in bacterial killing. Compared with peripheral blood neutrophils from
      +/+ mice, db/db neutrophils demonstrated a diminished respiratory burst when
      stimulated with S. aureus. However, bone marrow-derived neutrophils from +/+ and
      db/db mice showed comparable phagocytosis and bactericidal activity. Our results
      indicate that diabetic db/db mice are more susceptible to staphylococcal
      infection than their nondiabetic littermates and that persistent hyperglycemia
      modulates innate immunity in the diabetic host.

PMID- 19103775
TI  - RETRACTED: Sialic acids, important constituents and selective recognition factors
      of Pseudomonas aeruginosa, an opportunistic pathogen.
AB  - This article has been retracted.

PMID- 19103774
TI  - Salmonella enterica serovar typhimurium strains with regulated delayed
      attenuation in vivo.
AB  - Recombinant bacterial vaccines must be fully attenuated for animal or human hosts
      to avoid inducing disease symptoms while exhibiting a high degree of
      immunogenicity. Unfortunately, many well-studied means for attenuating Salmonella
      render strains more susceptible to host defense stresses encountered following
      oral vaccination than wild-type virulent strains and/or impair their ability to
      effectively colonize the gut-associated and internal lymphoid tissues. This thus
      impairs the ability of recombinant vaccines to serve as factories to produce
      recombinant antigens to induce the desired protective immunity. To address these
      problems, we designed strains that display features of wild-type virulent strains
      of Salmonella at the time of immunization to enable strains first to effectively
      colonize lymphoid tissues and then to exhibit a regulated delayed attenuation in
      vivo to preclude inducing disease symptoms. We recently described one means to
      achieve this based on a reversible smooth-rough synthesis of lipopolysaccharide O
      antigen. We report here a second means to achieve regulated delayed attenuation
      in vivo that is based on the substitution of a tightly regulated araC P(BAD)
      cassette for the promoters of the fur, crp, phoPQ, and rpoS genes such that
      expression of these genes is dependent on arabinose provided during growth. Thus,
      following colonization of lymphoid tissues, the Fur, Crp, PhoPQ, and/or RpoS
      proteins cease to be synthesized due to the absence of arabinose such that
      attenuation is gradually manifest in vivo to preclude induction of diseases
      symptoms. Means for achieving regulated delayed attenuation can be combined with
      other mutations, which together may yield safe efficacious recombinant attenuated
      Salmonella vaccines.

PMID- 19103776
TI  - GbdR regulates Pseudomonas aeruginosa plcH and pchP transcription in response to
      choline catabolites.
AB  - Pseudomonas aeruginosa hemolytic phospholipase C, PlcH, can degrade
      phosphatidylcholine (PC) and sphingomyelin in eukaryotic cell membranes and
      extracellular PC in lung surfactant. Numerous studies implicate PlcH in P.
      aeruginosa virulence. The phosphorylcholine released by PlcH activity on
      phospholipids is hydrolyzed by a periplasmic phosphorylcholine phosphatase, PchP.
      Both plcH gene expression and PchP enzyme activity are positively regulated by
      phosphorylcholine degradation products, including glycine betaine. Here we report
      that the induction of plcH and pchP transcription by glycine betaine is mediated
      by GbdR, an AraC family transcription factor. Mutants that lack gbdR are unable
      to induce plcH and pchP in media containing glycine betaine or choline and in
      phosphatidylcholine-rich environments, such as lung surfactant or mouse lung
      lavage fluid. In T broth containing choline, the gbdR mutant exhibited a 95%
      reduction in PlcH activity. In electrophoretic mobility shift assays, a GbdR
      maltose binding protein fusion bound specifically to both the plcH and pchP
      promoters. Promoter mapping, alignment of GbdR-regulated promoter sequences, and
      analysis of targeted promoter mutants that lack GbdR-dependent induction of
      transcription were used to identify a region necessary for GbdR-dependent
      transcriptional activation. GbdR also plays a significant role in plcH and pchP
      regulation within the mouse lung. Our studies suggest that GbdR is the primary
      regulator of plcH and pchP expression in PC-rich environments, such as the lung,
      and that pchP and other genes involved in phosphorylcholine catabolism are
      necessary to stimulate the GbdR-mediated positive feedback induction of plcH.

PMID- 19103777
TI  - Role of NADPH phagocyte oxidase in host defense against acute respiratory
      Acinetobacter baumannii infection in mice.
AB  - Acinetobacter baumannii is an emerging bacterial pathogen that rapidly develops
      multiple-drug resistance and is responsible for many nosocomial pulmonary
      infections. This study investigated the role of the NADPH phagocyte oxidase
      (phox) and inducible nitric oxide synthase (NOS2) in the host defense against
      respiratory infection with A. baumannii in mouse models of intranasal A.
      baumannii infection. gp91(phox-/-) mice showed higher susceptibility to A.
      baumannii infection than wild-type (WT) C57BL/6 mice, with significantly greater
      bacterial counts in their lungs (1,000-fold) (P < 0.005) and spleens (10-fold) (P
      < 0.05). Moreover, all of the gp91(phox-/-) mice succumbed to infection within 48
      h. In contrast, only a moderate increase in bacterial burdens was detected in the
      lungs of NOS2(-/-) mice, and all NOS2(-/-) mice survived infection. Compared to
      WT mice, the pulmonary influx of inflammatory cells and serum and local
      inflammatory cytokine/chemokine responses were not obviously impaired at 4 h and
      were significantly higher at 24 h (P < 0.05) in gp91(phox-/-) mice, but NADPH
      deficient neutrophils were unable to control bacterial replication and
      extrapulmonary dissemination. Thus, NADPH phagocyte oxidase appears to play a
      crucial role in the neutrophil-mediated host defense against A. baumannii.

PMID- 19103778
TI  - Proinflammatory response of human osteoblastic cell lines and osteoblast-monocyte
      interaction upon infection with Brucella spp.
AB  - The ability of Brucella spp. to infect human osteoblasts and the cytokine
      response of these cells to infection were investigated in vitro. Brucella
      abortus, B. suis, B. melitensis, and B. canis were able to infect the SaOS-2 and
      MG-63 osteoblastic cell lines, and the first three species exhibited
      intracellular replication. B. abortus internalization was not significantly
      affected by pretreatment of cells with cytochalasin D but was inhibited up to 92%
      by colchicine. A virB10 mutant of B. abortus could infect but not replicate
      within osteoblasts, suggesting a role for the type IV secretion system in
      intracellular survival. Infected osteoblasts produced low levels of chemokines
      (interleukin-8 [IL-8] and macrophage chemoattractant protein 1 [MCP-1]) and did
      not produce proinflammatory cytokines (IL-1beta, IL-6, and tumor necrosis factor
      alpha [TNF-alpha]). However, osteoblasts stimulated with culture supernatants
      from Brucella-infected human monocytes (THP-1 cell line) produced chemokines at
      levels 12-fold (MCP-1) to 17-fold (IL-8) higher than those of infected
      osteoblasts and also produced IL-6. In the inverse experiment, culture
      supernatants from Brucella-infected osteoblasts induced the production of IL-8,
      IL-1beta, IL-6, and TNF-alpha by THP-1 cells. The induction of TNF-alpha and IL
      1beta was largely due to granulocyte-macrophage colony-stimulating factor
      produced by infected osteoblasts, as demonstrated by inhibition with a specific
      neutralizing antibody. This study shows that Brucella can invade and replicate
      within human osteoblastic cell lines, which can directly and indirectly mount a
      proinflammatory response. Both phenomena may have a role in the chronic
      inflammation and bone and joint destruction observed in osteoarticular
      brucellosis.

PMID- 19103779
TI  - Validity of New Ballard Score until 7th day of postnatal life in moderately
      preterm neonates.
AB  - OBJECTIVE: The New Ballard Score (NBS) has been evaluated only until 96 h of age.
      We studied the validity and reliability of NBS for gestational age (GA)
      assessment on days 1, 5 and 7 of postnatal age (PNA). DESIGN AND SETTING: This
      prospective, analytical study was conducted in a level III neonatal unit.
      PATIENTS: Neonates born at a GA of 29-35 weeks (based on accurate last menstrual
      period (LMP)) were eligible. Encephalopathy, malformations, and unstable vitals
      were exclusion criteria. LMP-based GA was the gold standard. NBS was assessed
      within 24 h of birth by one rater, and two raters assessed NBS on days 5 and 7.
      All were blinded to LMP and one anothers' ratings. Recruitment continued until
      >100 subjects were enrolled with > or =25 in each LMP-based GA group: 29-30
      weeks, 31-32 weeks, 33-34 weeks and 35 weeks. MAIN OUTCOME: Correlation of GA
      assessed on day 7 with gold standard. RESULTS: 129 neonates were studied. NBS
      based GA on days 5 or 7 did not differ from the gold standard GA by more than 2
      weeks in any subject. On day 7, NBS overestimated GA in 26.7% and underestimated
      GA in 19.8% cases; all discrepancies were < or =2 wks. Compared to gold standard
      GA, the intra-class correlations (ICCs) of the gold standard GA and the NBS-based
      GA of the day 1 rater, day 5 rater and day 7 rater were 0.94, 0.94 and 0.92,
      respectively. ICCs for inter-rater reliability on day 5 and day 7 were 0.97 and
      0.96, respectively. Compared to the day 1 rater's raw NBS, the ICCs of day 5 and
      day 7 raters' total scores were 0.98 and 0.97, respectively; of day 5 and day 7
      raters' neurological scores were 0.98 and 0.97; and of day 5 and day 7 raters'
      physical scores were 0.92 and 0.88. All ICCs mentioned above had p values <0.001.
      CONCLUSIONS: NBS is a valid and reliable clinical tool for GA assessment until
      day 7. It slightly overestimates the GA with increasing PNA. Neurological signs
      are more reliable than physical ones.

PMID- 19103780
TI  - Klebsiella pneumoniae: caught on film.

PMID- 19103781
TI  - Relationship between vitamin D and alkaline phosphatase in very-low-birthweight
      infants.

PMID- 19103782
TI  - Postnatal corticosteroids to treat or to prevent chronic lung disease: a survey
      of neonatologists' practices.

PMID- 19103783
TI  - Infection control during administration of parenteral nutrition in preterm
      babies.

PMID- 19103784
TI  - Oxygen and living at altitude.

PMID- 19103785
TI  - Diagnosis of mitochondrial DNA depletion syndromes.

PMID- 19103788
TI  - A giant aneurysm arising from renal angiomyolipoma in tuberous sclerosis.

PMID- 19103789
TI  - Simultaneous detection of mitochondrial DNA depletion and single-exon deletion in
      the deoxyguanosine gene using array-based comparative genomic hybridisation.
AB  - Intragenic exonic deletions, which cannot be detected by direct DNA sequencing,
      are a common cause of Mendelian disease. Array-based comparative genomic
      hybridisation (aCGH) is now widely used for the clinical diagnosis of large
      chromosomal deletions, but not small deletions or analysis of the mitochondrial
      genome. An oligonucleotide-based microarray that provides high-density coverage
      of the entire mitochondrial genome and nuclear genes related to mitochondrial
      disorders has been developed. In this report, the case of an infant referred with
      tyrosinaemia on newborn screening who developed liver failure is presented. DNA
      sequencing revealed a heterozygous missense mutation (c.679G>A, p.E227K) in the
      deoxyguanosine gene (DGUOK). Oligonucleotide aCGH allowed simultaneous detection
      of an intragenic heterozygous deletion of exon 4 of DGUOK and mitochondrial DNA
      depletion in blood and liver. Screening of the parents' DNA samples indicated
      that the patient was compound heterozygous for these mutations. An older sibling
      who had died from liver failure was then retrospectively diagnosed with the same
      mutations. This report shows the clinical utility of this oligoarray in the
      detection of changes in DNA copy number in both the mitochondrial and nuclear
      genomes, thus greatly improving the molecular diagnosis of mitochondrial
      disorders caused by nuclear genes involved in mitochondrial DNA biosynthesis.

PMID- 19103790
TI  - Lateral deviation of toes requires lateral thinking.

PMID- 19103791
TI  - Giant cell astrocytomas in tuberous sclerosis complex.

PMID- 19103792
TI  - Gelofusine--not even a suggestion of a link with NEC.

PMID- 19103793
TI  - EpiPen training provided to parents of children with food allergies.

PMID- 19103796
TI  - Analogical problem solving in children with verbal and nonverbal learning
      disabilities.
AB  - Analogical reasoning--perceiving similarities in different situations and the
      transfer of such information--facilitates learning and understanding. However,
      children with learning disabilities (LD) typically demonstrate deficits in such
      information processing strategies. In this study, we investigated the analogical
      problem-solving differences between children with verbal learning disabilities
      (VLD), nonverbal learning disabilities (NLD), or non-LD. Results indicated better
      recall of component stories by children without disabilities but no significant
      differences between the NLD and VLD participants. However, the success rate for
      target problem solving was much lower for the NLD group than for the VLD and non
      LD groups. The poor performance of the NLD children may be attributed to some of
      their characteristic weaknesses, critical for analogical problem solving. Yet the
      VLD group was significantly weaker in recall than the non-LD group, but this did
      not hamper their analogical problem-solving abilities. These findings confirm
      that analogical thinking requires more than memory.

PMID- 19103797
TI  - Effectiveness of a test-taking strategy on achievement in essay tests for
      students with learning disabilities.
AB  - Research was conducted to ascertain if an essay-writing strategy was effective at
      improving the achievement on essay tests for 7th- and 8th-grade students with
      reading and writing disabilities. Students were assigned via a stratified random
      sample to treatment or control group. Student scores were also compared to
      students without learning disabilities nominated by teachers as average writers.
      A 6-step essay strategy was taught that included analyzing the essay prompt,
      outlining, writing a response, and reviewing the answer. On the posttest,
      intervention group students significantly outperformed control group students on
      essay measures related to strategy use, content, and organization. There was no
      significant difference between treatment group and students without learning
      disabilities on posttest measures of content and organization.

PMID- 19103798
TI  - The mental health of canadians with self-reported learning disabilities.
AB  - There has been growing concern as to the mental health status of persons with
      learning disabilities (PWLD). This study examined rates of mental health problems
      among PWLD aged 15 to 44 years using a large, nationally representative data set.
      PWLD were more than twice as likely to report high levels of distress,
      depression, anxiety disorders, suicidal thoughts, visits to mental health
      professionals, and poorer overall mental health than were persons without
      disabilities (PWOD). Multivariate regression analyses determined that these
      significantly higher rates of mental health problems remained for all six
      measures after controlling for confounding factors including income, education,
      social support, and physical health. Differences found in the older adult sample
      (ages 30-44) were even larger than in the adolescent sample (ages 15-21) for
      suicidal thoughts, depression, and distress. Males with learning disabilities
      were more likely to report depressive episodes, anxiety disorders, and
      consultations with health professionals, whereas females with learning
      disabilities were more likely to report high distress, suicidal thoughts, and
      poor general mental health relative to PWOD. On balance, learning disabilities
      were not found to be more detrimental to mental health for one gender or the
      other.

PMID- 19103799
TI  - Technical features of curriculum-based measures for beginning writers.
AB  - The purpose of the two studies reported in this article was to examine technical
      features of curriculum-based measures for beginning writers. In Study 1, 50 first
      graders responded to word copying, sentence copying, and story prompts. In Study
      2, 50 additional first graders responded to letter, picture-word, picture-theme,
      and photo prompts. In both studies, 3- to 5-minute prompts were administered in
      winter and spring and scored using a variety of quantitative procedures. Students
      were also administered the Test of Written Language-Third Edition , and teacher
      ratings and scores on a district rubric for writing were collected. Test-retest
      (Study 1 only) and alternate-form reliability, criterion validity, and winter-to
      spring growth were examined for each measure. Sentence-copying, story, picture
      word, and photo prompts emerged as promising beginning-writing measures. Findings
      have implications for monitoring student progress within a seamless and flexible
      system across ages and skill levels.

PMID- 19103800
TI  - Implementation of response to intervention: a snapshot of progress.
AB  - This article provides a snapshot of how all 50 states are progressing with the
      development and implementation of response-to-intervention (RtI) models 1 year
      after the final regulations for the Individuals with Disabilities Education Act
      were passed. Data were collected through a review of existing state department of
      education Web sites and conversations with representatives in each state
      department of education. Information related to RtI model type, implementation
      status, professional development, criteria for eligibility, and specific features
      of individual state RtI models are presented. Findings indicate that most states
      are in some phase of RtI development, although approaches vary widely throughout
      the country. Implications for research and practice are discussed.

PMID- 19103801
TI  - Pushing the frontiers of development.
AB  - A joint meeting of the Japanese and French societies for Developmental Biology,
      entitled ;Frontiers in Developmental Biology', was recently held in Giens,
      France. The organizers, Patrick Lemaire and Shinichi Aizawa, showcased some of
      the rapid progress in the field that has been made possible through the use of
      modern large-scale network analyses, and of an increasingly sophisticated array
      of tools and ideas from microscopy, mathematics and computer science.

PMID- 19103802
TI  - Growing models of vertebrate limb development.
AB  - The developing limb has been a very influential system for studying pattern
      formation in vertebrates. In the past, classical embryological models have
      explained how patterned structures are generated along the two principal axes of
      the limb: the proximodistal (shoulder to finger) and anteroposterior (thumb to
      little finger) axes. Over time, the genetic and molecular attributes of these
      patterning models have been discovered, while the role of growth in the
      patterning process has been only recently highlighted. In this review, we discuss
      these recent findings and propose how the various models of limb patterning can
      be reconciled.

PMID- 19103803
TI  - Distinct functions of Wnt/beta-catenin signaling in KV development and cardiac
      asymmetry.
AB  - The Wnt/beta-catenin pathway exhibits distinct and developmental stage-specific
      roles during cardiogenesis. However, little is known about the molecular
      mechanisms of Wnt/beta-catenin signaling in the establishment of cardiac left
      right (LR) asymmetry. Using zebrafish as an animal model, we show here that
      Wnt/beta-catenin signaling is differentially required in cardiac LR patterning.
      At an early stage, during asymmetric signal generation, Wnt/beta-catenin
      signaling is necessary for Kupffer's vesicle development and for the regulation
      of both heart and visceral laterality. At a later stage, during asymmetric signal
      propagation, excessive Wnt/beta-catenin signaling inhibits the transmission of
      asymmetric cues from the lateral plate mesoderm (LPM) to the cardiac field but
      not to the developing gut; as such, it only regulates heart laterality. Molecular
      analysis identifies Gata4 as the downstream target of Wnt/beta-catenin signaling
      in the cardiac field that responds to the Wnt/beta-catenin signaling and
      regulates the competence of the heart field to express left-sided genes. In
      summary, our results reveal a previously unexpected role of Wnt-Gata4 signaling
      in the control of asymmetric signal propagation from the LPM to the cardiac
      field.

PMID- 19103804
TI  - Identification of a transient subpial neurogenic zone in the developing dentate
      gyrus and its regulation by Cxcl12 and reelin signaling.
AB  - One striking feature of dentate gyrus development, distinct from the other
      cortical structures, is the relocation of neural precursors from the ventricular
      zone to the forming dentate pole to produce a lifelong neurogenic subgranular
      zone (SGZ). In this study, we demonstrate that dentate progenitors first dwell
      for up to 1 week in a previously unrecognized neurogenic zone intimately
      associated with the pial meningeal surface lining the outer edge of the forming
      dentate. This zone also serves as the organizational matrix for the initial
      formation of the dentate glial scaffolding. Timely clearance of neural precursors
      from their transient location depends on reelin, whereas initial formation of
      this transient stem cell niche requires Cxcl12-Cxcr4 signaling. The final
      settlement of the neural precursors at the subgranular zone relies on a pertussis
      toxin-sensitive pathway independent of Cxcl12-Cxcr4 signaling. Furthermore,
      genetic fate-mapping analysis suggests that subpial precursors contribute to the
      SGZ formation. These results demonstrate that the relocation of neural precursors
      in the dentate gyrus consists of discrete steps regulated by multiple pathways.

PMID- 19103805
TI  - Met and the epidermal growth factor receptor act cooperatively to regulate final
      nephron number and maintain collecting duct morphology.
AB  - Ureteric bud (UB) branching during kidney development determines the final number
      of nephrons. Although hepatocyte growth factor and its receptor Met have been
      shown to stimulate branching morphogenesis in explanted embryonic kidneys, loss
      of Met expression is lethal during early embryogenesis without obvious kidney
      abnormalities. Met(fl/fl);HoxB7-Cre mice, which lack Met expression selectively
      in the UB, were generated and found to have a reduction in final nephron number.
      These mice have increased Egf receptor expression in both the embryonic and adult
      kidney, and exogenous Egf can partially rescue the branching defect seen in
      kidney explants. Met(fl/fl);HoxB7-Cre;wa-2/wa-2 mice, which lack normal Egfr and
      Met signaling, exhibit small kidneys with a marked decrease in UB branching at
      E14.5 as well as a reduction in final glomerular number. These mice developed
      progressive interstitial fibrosis surrounding collecting ducts with kidney
      failure and death by 3-4 weeks of age. Thus, in support of previous in vitro
      findings, Met and the Egf receptor can act cooperatively to regulate UB branching
      and mediate maintenance of the normal adult collecting duct.

PMID- 19103806
TI  - UBF levels determine the number of active ribosomal RNA genes in mammals.
AB  - In mammals, the mechanisms regulating the number of active copies of the
      approximately 200 ribosomal RNA (rRNA) genes transcribed by RNA polymerase I are
      unclear. We demonstrate that depletion of the transcription factor upstream
      binding factor (UBF) leads to the stable and reversible methylation-independent
      silencing of rRNA genes by promoting histone H1-induced assembly of
      transcriptionally inactive chromatin. Chromatin remodeling is abrogated by the
      mutation of an extracellular signal-regulated kinase site within the high
      mobility group box 1 domain of UBF1, which is required for its ability to bend
      and loop DNA in vitro. Surprisingly, rRNA gene silencing does not reduce net rRNA
      synthesis as transcription from remaining active genes is increased. We also show
      that the active rRNA gene pool is not static but decreases during
      differentiation, correlating with diminished UBF expression. Thus, UBF1 levels
      regulate active rRNA gene chromatin during growth and differentiation.

PMID- 19103807
TI  - PARP-1 ensures regulation of replication fork progression by homologous
      recombination on damaged DNA.
AB  - Poly-ADP ribose polymerase 1 (PARP-1) is activated by DNA damage and has been
      implicated in the repair of single-strand breaks (SSBs). Involvement of PARP-1 in
      other DNA damage responses remains controversial. In this study, we show that
      PARP-1 is required for replication fork slowing on damaged DNA. Fork progression
      in PARP-1(-/-) DT40 cells is not slowed down even in the presence of DNA damage
      induced by the topoisomerase I inhibitor camptothecin (CPT). Mammalian cells
      treated with a PARP inhibitor or PARP-1-specific small interfering RNAs show
      similar results. The expression of human PARP-1 restores fork slowing in PARP-1(
      /-) DT40 cells. PARP-1 affects SSB repair, homologous recombination (HR), and
      nonhomologous end joining; therefore, we analyzed the effect of CPT on DT40
      clones deficient in these pathways. We find that fork slowing is correlated with
      the proficiency of HR-mediated repair. Our data support the presence of a novel
      checkpoint pathway in which the initiation of HR but not DNA damage delays the
      fork progression.

PMID- 19103808
TI  - The sympathetic tone mediates leptin's inhibition of insulin secretion by
      modulating osteocalcin bioactivity.
AB  - The osteoblast-secreted molecule osteocalcin favors insulin secretion, but how
      this function is regulated in vivo by extracellular signals is for now unknown.
      In this study, we show that leptin, which instead inhibits insulin secretion,
      partly uses the sympathetic nervous system to fulfill this function. Remarkably,
      for our purpose, an osteoblast-specific ablation of sympathetic signaling results
      in a leptin-dependent hyperinsulinemia. In osteoblasts, sympathetic tone
      stimulates expression of Esp, a gene inhibiting the activity of osteocalcin,
      which is an insulin secretagogue. Accordingly, Esp inactivation doubles
      hyperinsulinemia and delays glucose intolerance in ob/ob mice, whereas
      Osteocalcin inactivation halves their hyperinsulinemia. By showing that leptin
      inhibits insulin secretion by decreasing osteocalcin bioactivity, this study
      illustrates the importance of the relationship existing between fat and skeleton
      for the regulation of glucose homeostasis.

PMID- 19103809
TI  - CLIP-170 tracks growing microtubule ends by dynamically recognizing composite
      EB1/tubulin-binding sites.
AB  - The microtubule cytoskeleton is crucial for the internal organization of
      eukaryotic cells. Several microtubule-associated proteins link microtubules to
      subcellular structures. A subclass of these proteins, the plus end-binding
      proteins (+TIPs), selectively binds to the growing plus ends of microtubules.
      Here, we reconstitute a vertebrate plus end tracking system composed of the most
      prominent +TIPs, end-binding protein 1 (EB1) and CLIP-170, in vitro and dissect
      their end-tracking mechanism. We find that EB1 autonomously recognizes specific
      binding sites present at growing microtubule ends. In contrast, CLIP-170 does not
      end-track by itself but requires EB1. CLIP-170 recognizes and turns over rapidly
      on composite binding sites constituted by end-accumulated EB1 and tyrosinated
      alpha-tubulin. In contrast to its fission yeast orthologue Tip1, dynamic end
      tracking of CLIP-170 does not require the activity of a molecular motor. Our
      results demonstrate evolutionary diversity of the plus end recognition mechanism
      of CLIP-170 family members, whereas the autonomous end-tracking mechanism of EB
      family members is conserved.

PMID- 19103810
TI  - Nanotubes, exosomes, and nucleic acid-binding peptides provide novel mechanisms
      of intercellular communication in eukaryotic cells: implications in health and
      disease.
AB  - The prevailing view that eukaryotic cells are restrained from intercellular
      exchange of genetic information has been challenged by recent reports on
      nanotubes, exosomes, apoptotic bodies, and nucleic acid-binding peptides that
      provide novel pathways for cell-cell communication, with implications in health
      and disease.

PMID- 19103811
TI  - EBs clip CLIPs to growing microtubule ends.
AB  - Proteins that track growing microtubule (MT) ends are important for many aspects
      of intracellular MT function, but the mechanism by which these +TIPs accumulate
      at MT ends has been the subject of a long-standing controversy. In this issue,
      Bieling et al. (Bieling, P., S. Kandels-Lewis, I.A. Telley, J. van Dijk, C.
      Janke, and T. Surrey. 2008. J. Cell Biol. 183:1223-1233) reconstitute plus end
      tracking of EB1 and CLIP-170 in vitro, which demonstrates that CLIP-170 plus end
      tracking is EB1-dependent and that both +TIPs rapidly exchange between a soluble
      and a plus end-associated pool. This strongly supports the hypothesis that plus
      end tracking depends on a biochemical property of growing MT ends, and that the
      characteristic +TIP comets result from the generation of new +TIP binding sites
      through MT polymerization in combination with the exponential decay of these
      binding sites.

PMID- 19103812
TI  - A breath of fresh air for acute oxygen treatment.

PMID- 19103813
TI  - A brief history of the development of mannequin simulators for clinical education
      and training.
AB  - Simulation for medical and healthcare applications, although still in a
      relatively nascent stage of development, already has a history that can inform
      the process of further research and dissemination. The development of mannequin
      simulators used for education, training, and research is reviewed, tracing the
      motivations, evolution to commercial availability, and efforts toward assessment
      of efficacy of those for teaching cardiopulmonary resuscitation, cardiology
      skills, anaesthesia clinical skills, and crisis management. A brief overview of
      procedural simulators and part-task trainers is also presented, contrasting the
      two domains and suggesting that a thorough history of the 20+ types of simulator
      technologies would provide a useful overview and perspective. There has been
      relatively little cross fertilisation of ideas and methods between the two
      simulator domains. Enhanced interaction between investigators and integration of
      simulation technologies would be beneficial for the dissemination of the concepts
      and their applications.

PMID- 19103814
TI  - Bubble trouble: a review of diving physiology and disease.
AB  - Exposure to the underwater environment for recreational or occupational purposes
      is increasing. Approximately 7 million divers are active worldwide and 500,000
      more are training every year. Diving related illnesses are consequently an
      increasingly common clinical problem with over 1000 cases of decompression
      illness reported annually in the USA alone. Divers are exposed to a number of
      physiological risks as a result of the hyperbaric underwater environment
      including: the toxic effects of hyperbaric gases, the respiratory effects of
      increased gas density, drowning, hypothermia and bubble related pathophysiology.
      Understanding the nature of this pathophysiology provides insight into
      physiological systems under stress and as such may inform translational research
      relevant to clinical medicine. We will review current diving practice, the
      physics and physiology of the hyperbaric environment, and the pathophysiology and
      treatment of diving related diseases. We will discuss current developments in
      diving research and some potential translational research areas.

PMID- 19103815
TI  - The added value of peripheral blood cell morphology in the diagnosis and
      management of infectious diseases--part 1: basic concepts.
AB  - As automated blood cell analysers and sophisticated diagnostic technologies
      become widespread, requests for peripheral blood smear (PBS) examination--for the
      diagnosis of infectious diseases--diminish. Yet, PBS examination can provide
      rapid and invaluable information on infection--host susceptibility, aetiology,
      severity, and systemic impact. Besides direct visualisation of certain
      microorganisms (for example, Plasmodium, Ehrlichia), PBS examination may detect
      characteristic footprints left by various infections on the morphology of blood
      cells, thus yielding the cytologic clues of the disease (for example, Dohle
      bodies, haemophagocytosis). Additionally, PBS examination may disclose certain
      infection predisposing conditions (for example, May-Hegglin anomaly,
      hyposplenism), and several infection related haematological and systemic
      complications. Combined with a careful medical history and physical examination
      data, all this information may yield a speedy diagnosis, a rationalised
      diagnostic work-up, and timely initiation of treatment. The intention of the
      following review is to highlight the value of PBS, and recommend that PBS
      examination should be fostered in the diagnostic work-up of infectious diseases.

PMID- 19103816
TI  - The added value of peripheral blood cell morphology in the diagnosis and
      management of infectious diseases--part 2: illustrative cases.
AB  - The previous review dealt with the diagnostic yield of peripheral blood smear
      examination with regard to diagnosis of infectious diseases. In addition to the
      clinical data, it can provide information of major clinical significance. At
      times, it can even replace additional, costly and time-consuming diagnostic
      modalities. The following clinical vignettes, which are discussed briefly,
      support these arguments.

PMID- 19103817
TI  - Targeting residual cardiovascular risk: raising high-density lipoprotein
      cholesterol levels.
AB  - The last 20 years have witnessed dramatic reductions in cardiovascular risk using
      3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors ("statins") to lower
      levels of low-density lipoprotein cholesterol (LDL-C). Using this approach one
      can achieve a reduction in the risk of major cardiovascular events of 21% for
      every 1 mmol/l (39 mg/dl) decrease in LDL-C. However, despite intensive therapy
      with high dose "statins" to lower LDL-C levels below 2.6 mmol/l (100 mg/dl), the
      risk of a major cardiovascular event in patients with established coronary artery
      disease remains significant at a level approaching an annual risk of 9%, paving
      the way for new strategies for reducing the residual cardiovascular risk in this
      patient group. Early epidemiological studies have identified low levels of high
      density lipoprotein cholesterol (HDL-C) (<1.0 mmol/l or 40 mg/dl), a common
      feature of type 2 diabetes mellitus and the metabolic syndrome, to be an
      independent determinant of increased cardiovascular risk. The beneficial effects
      of HDL-C on the cardiovascular system have been attributed to its ability to
      remove cellular cholesterol, as well as its anti-inflammatory, antioxidant and
      antithrombotic properties, which act in concert to improve endothelial function
      and inhibit atherosclerosis, thereby reducing cardiovascular risk. As such,
      raising HDL-C in patients with aggressively lowered LDL-C provides an additional
      strategy for addressing the residual cardiovascular risk present in these
      patients groups. Studies suggest that for every 0.03 mmol/l (1.0 mg/dl) increase
      in HDL-C, cardiovascular risk is reduced by 2-3%. Raising HDL-C can be achieved
      by both lifestyle changes and pharmacological means, the former of which include
      smoking cessation, aerobic exercise, weight loss and dietary manipulation.
      Therapeutic strategies have included niacin, fibrates, thiazolidinediones and
      bile acid sequestrants. Newly developed pharmacological agents include
      apolipoprotein A-I mimetics and the cholesteryl ester transfer protein (CETP)
      inhibitors, JTT-705 and torcetrapib, the latter of which has been recently
      withdrawn from clinical testing because of serious adverse effects. Emerging
      experimental studies investigating the complex pathways of HDL metabolism have
      identified several new targets for raising HDL-C with new pharmaceutical agents
      currently in development. For the time being, the long-acting formulations of
      nicotinic acid remain the most effective and best tolerated pharmacological
      strategy for raising HDL-C in patients already on statin therapy to control LDL
      C. Therefore, raising HDL-C represents an important strategy for reducing
      residual cardiovascular risk in patients already optimally treated with statins,
      and should lead to further improvements in clinical outcomes in these patient
      groups.

PMID- 19103818
TI  - The Royal Philanthropic Expedition of the Vaccine: a landmark in the history of
      public health.
AB  - In 1979, smallpox officially became the first disease ever to be eradicated by
      mankind. The global efforts to defeat this dreadful pandemic, however, started
      almost two centuries before. One of the most important, and sometimes forgotten,
      events in the fight against smallpox was the Royal Philanthropic Expedition of
      the Vaccine, commissioned by Charles IV of Spain to physicians Francisco Xavier
      Balmis y Berenguer and Jose Salvany in 1804. The aim of this expedition was to
      take the smallpox vaccine, discovered by Jenner, to Spain's territories in the
      Americas and in the Far East. After several years of vaccination in modern day
      Puerto Rico, Cuba, Venezuela, Ecuador, Peru, Bolivia, Chile, Mexico and the
      Philippines, the expedition returned to Europe. To this day, the Balmis and
      Salvany expedition remains a great example of international cooperation, and a
      landmark in the history of public health.

PMID- 19103819
TI  - Improvement in the management of acutely poisoned patients using an electronic
      database, prospective audit and targeted educational intervention.
AB  - PROBLEM: The need to improve the clinical assessment and management of acutely
      poisoned patients presenting to an NHS hospital emergency department (ED).
      DESIGN: Creation of an electronic clinical toxicology database to prospectively
      collect all aspects of clinical information on poisoned-patient presentations.
      Systematic analysis of collated information to identify shortfalls in patient
      assessment and management. Bimonthly audit meetings, and design and
      implementation of educational interventions to address identified shortfalls.
      Ongoing audit to demonstrate continued improvement in patient care. BACKGROUND
      AND SETTING: ED in tertiary-level inner-city London teaching hospital. Study
      conducted by staff from the ED and clinical toxicology service. KEY MEASURES FOR
      IMPROVEMENT: Demonstration of overall reduction in the incidence of predefined
      shortfalls in patient assessment and management during 12-month study period.
      STRATEGIES FOR IMPROVEMENT: Targeted educational lectures and case-based clinical
      scenarios addressing identified deficiencies in the knowledge required to
      effectively manage poisoned patients. Weekly case-based anonymised feedback
      report sent electronically to staff involved in caring for poisoned patients.
      EFFECTS OF CHANGE: Implementation of targeted teaching of ED staff and regular
      electronic distribution of teaching cases. Between the first and second 6 months
      of the study, there was a significant increase in the proportion of presentations
      for which clinical management was graded as "good" (77.6% to 89.4%, p<0.0001) and
      a significant reduction in the proportion of "major" (9.9% to 5.8%, p = 0.012)
      and "minor" (12.6% to 4.8%, p<0.0001) shortfalls. LESSONS LEARNT: Systematic
      collection of clinical information, using a dedicated electronic database and
      subsequent review and audit of collated data by interested clinicians, enabled
      design and implementation of targeted educational interventions to address
      shortfalls in patient management. This process has led to significant
      improvements in the clinical care of acutely poisoned patients presenting to the
      ED.

PMID- 19103821
TI  - Fever and eosinophilia in a returned traveller.

PMID- 19103820
TI  - Radiation effects on the intima-media thickness of the common carotid artery in
      post-radiotherapy patients with head and neck malignancy.
AB  - BACKGROUND: Post-radiation large vessel injury has not received as much attention
      as microvascular irradiation injury. A few studies have shown that common carotid
      intima-media thickness (IMT) is increased after radiotherapy to the head and
      neck. However, in most of these studies, the irradiated subjects also had other
      major risk factors for atherosclerosis. In this study, irradiated subjects with
      major risk factors such as hypertension, diabetes, history of previous
      cerebrovascular accident and connective tissue disorder were excluded. OBJECTIVE:
      To show in a cross-sectional study if radiotherapy to the carotid area has any
      effect on the IMT of the common carotid artery. SUBJECTS AND METHODS: 13 patients
      with head and neck malignancies who had completed radiotherapy to the carotid
      region at least 1 year previously underwent ultrasound of the carotid artery. IMT
      measurements were compared with those of 13 healthy controls, matched for age,
      sex and race, with no history of radiotherapy. RESULTS: The irradiated subjects
      had significantly larger IMT measurements (mean 0.74 mm) than the non-irradiated
      subjects (mean 0.46 mm). The difference was significant (p<0.001) with a
      confidence interval of 95%. CONCLUSIONS: This study shows that there is a
      measurable, significant (p<0.001) increase in IMT of the common carotid artery
      after radiotherapy for head and neck malignancy compared with non-irradiated
      matched controls. This knowledge is important for risk-benefit assessment of
      prophylactic or therapeutic neck irradiation. Increased awareness of this
      complication should provide an opportunity to intervene and prevent future
      cerebrovascular accidents in the majority of such patients.

PMID- 19103822
TI  - Enterobius infestation in suspected appendicitis.

PMID- 19103825
TI  - To lower or not to lower? Making sense of the latest research on intensive
      glycaemic control and cardiovascular outcomes.

PMID- 19103826
TI  - Applying evidence: what's the next action?

PMID- 19103827
TI  - Mothers were less likely to be depressed after a structured behavioural
      intervention for infant sleep problems.

PMID- 19103828
TI  - Review: varenicline, bupropion, and nicotine replacement therapies are effective
      for smoking cessation at 6 or 12 months.

PMID- 19103829
TI  - Review: exercise plus diet prevents type 2 diabetes.

PMID- 19103830
TI  - Intensive glucose control did not prevent important complications in type 2
      diabetes.

PMID- 19103831
TI  - Intensive glucose control increased mortality and did not prevent cardiovascular
      events in type 2 diabetes.

PMID- 19103832
TI  - Benefits of early intensive glucose control in preventing diabetes-related
      complications were sustained for up to 10 years.

PMID- 19103833
TI  - Review: culturally appropriate health education improves glycaemic control in
      members of ethnic minority groups with diabetes.

PMID- 19103835
TI  - A nurse-delivered intervention was effective for depression in patients with
      cancer.

PMID- 19103834
TI  - Review: short-term medical use of cannabis increases risk of non-serious adverse
      effects.

PMID- 19103836
TI  - Review: multicomponent educational interventions improve some outcomes in
      predialysis and dialysis care.

PMID- 19103837
TI  - Clinically indicated and routine replacement of peripheral intravenous catheters
      did not differ for catheter failure.

PMID- 19103838
TI  - Review: chewing gum after abdominal surgery reduces time to return of bowel
      function but not length of hospital stay.

PMID- 19103839
TI  - Normal food at will and nil-by-mouth enteral feeding after major upper GI surgery
      did not differ for mortality or morbidity.

PMID- 19103840
TI  - Initial refeeding with a soft diet was better than a clear liquid diet for length
      of hospital stay in mild acute pancreatitis.

PMID- 19103841
TI  - Review: psychological interventions prevent depression after stroke.

PMID- 19103842
TI  - Review: providing information improves subjective outcomes but may not improve
      clinical outcomes in patients with stroke or their carers.

PMID- 19103843
TI  - General practitioners' advice to use topical rather than oral ibuprofen resulted
      in equivalent effects on chronic knee pain.

PMID- 19103844
TI  - Excess mortality after HIV seroconversion has greatly decreased in the past 10
      years.

PMID- 19103845
TI  - Review: quality improvement interventions reduce unnecessary prescription of
      antibiotics for outpatients.

PMID- 19103847
TI  - Patients felt greater personal control and emotional comfort in hospital when
      they felt secure, informed, and valued.

PMID- 19103846
TI  - Men were surprised by the severity of symptoms they experienced after
      laparoscopic radical prostatectomy.

PMID- 19103848
TI  - Prioritising mealtime care, patient choice, and nutritional assessment were
      important for older inpatients' mealtime experiences.

PMID- 19103849
TI  - Peer relationships were important to the experience of thriving in some, but not
      all, nursing home residents.

PMID- 19103850
TI  - Many older people felt that electronic care surveillance increased their safety
      and enabled them to live alone in their own homes.

PMID- 19103851
TI  - The role of haemoglobin A(2) testing in the diagnosis of thalassaemias and
      related haemoglobinopathies.
AB  - The increase in haemoglobin (Hb)A(2) level is the most significant parameter in
      the identification of beta thalassaemia carriers. However, in some cases the
      level of HbA(2) is not typically elevated and some difficulties may arise in
      making the diagnosis. For these reasons the quantification of HbA(2) has to be
      performed with great accuracy and the results must be interpreted together with
      other haematological and biochemical evidence. The present document includes
      comments on the need for accuracy and standardisation, and on the interpretation
      of the HbA(2) value, reviewing the most crucial aspects related to this test. A
      practical flow-chart is presented to summarise the significance of HbA(2)
      estimation in different thalassaemia syndromes and related haemoglobinopathies.

PMID- 19103852
TI  - Starting neonatal screening for haemoglobinopathies in The Netherlands.
AB  - Neonatal screening for haemoglobinopathies started in The Netherlands on 1
      January 2007. The method of choice, high-performance liquid chromatography, and
      the universal setting have shown that the predicted incidence is indeed present
      in the country. Patients and carriers are reported in order to prevent morbidity,
      and for the primary prevention of serious haemoglobinopathies. Background,
      preceding discussion, health gain, implementation, provisional results and ethics
      issues are discussed, as well as matters concerning technology, know-how, and
      ongoing and future developments.

PMID- 19103853
TI  - Neonatal haemoglobinopathy screening in Spain.
AB  - The prevalence of variant haemoglobins in Spain is increasing as a result of
      recent African immigration. Of the 19 regions of Spain, 13 have more than 1% of
      residents of African origin or ethnicity. Haemoglobinopathy prevalence is
      heterogeneous. Some cases of sickle cell disease (SCD) and sickle cell trait have
      been found in autochthonous individuals, but this is very rare. Most of the
      studies of SCD prevalence in Spain are incomplete or focused on a few
      geographical regions. When screening has been carried out regardless of ethnic
      origin, overall haemoglobinopathy prevalence has varied from 0.14% to 0.94% and
      the estimated prevalence of SCD has varied from 0.001 (in Extremadura) to 0.03
      (in Aragon). A registry for SCD maintained by the Spanish Society of Paediatric
      Haematology shows that in the last 4 years the prevalence of SCD has increased
      threefold. Only two Spanish Communities (Extremadura and Madrid) are running an
      official neonatal screening programme for SCD. Other Spanish Communities have
      finished local pilot studies and are expected to establish neonatal screening
      programmes shortly. Catalonia, the Spanish community with the highest African
      immigration flow and SCD genetic impact, has not yet established an official
      programme for SCD neonatal screening; screening currently depends on individual
      hospital policies and is restricted to at-risk ethnic groups. Studies performed
      so far suggest that universal screening should be recommended for regions with a
      high annual birth rate and SCD prevalence (Catalonia and Madrid, for example),
      with a targeted policy being restricted to regions with low annual birth rate and
      SCD prevalence.

PMID- 19103854
TI  - Implementation of universal newborn bloodspot screening for sickle cell disease
      and other clinically significant haemoglobinopathies in England: screening
      results for 2005-7.
AB  - Early results from the National Health Service Sickle Cell and Thalassaemia
      Screening programme covering the whole of England are reported following the
      implementation of the national newborn blood-spot screening programme. Of the 13
      laboratories performing screening, 10 chose high-performance liquid
      chromatography as the first screen, with isoelectric focusing as the second
      confirmatory test. Screening results for April 2005 to March 2007 are presented
      and include data from all the laboratories screening newborns in England, and
      almost 1.2 million infants. The screen-positive results show a national birth
      prevalence of almost 1 in 2000. The birth prevalence in London is five times that
      of most of the rest of the country. Over 17,000 carriers have been identified.
      Approximately seven per 1000 samples are reported as post-transfusion with wide
      ethnic category variation. Given the prevalence of the conditions, and coverage
      by ethnicity, 3-4 screen-positive cases could be missed each year. National
      implementation of newborn screening in England has increased the number of
      children identified with sickle cell disease, in many areas almost doubling the
      workload. Underascertainment of the condition has allowed a downplaying of the
      scale of need. It may also have contributed to infant mortality rates in urban
      areas as babies died without a diagnosis or treatment. The value of a co
      ordinated national approach to policy development and implementation is
      emphasised by the English experience. The programme provides a model for Europe
      as well as other countries with significant minority populations, such as Canada.
      Potentially it also offers important lessons for Africa where the World Health
      Organization is supporting the introduction of newborn screening.

PMID- 19103855
TI  - Neonatal screening for sickle cell disease in France.
AB  - BACKGROUND: As a result of population growth in African-Caribbean regions of
      overseas France, and now immigration essentially from North and sub-Saharan
      Africa to mainland France, neonatal screening for sickle cell disease (SCD) has
      been performed in France since 1985 in Guadalupe and dependencies, as a universal
      test. After several pilot studies, screening was gradually extended to mainland
      France in 1996. Since 2000, the test has been performed at national level for all
      newborns defined as being "at risk" for SCD based on ethnic origin. METHODS: A
      dry blood sample is obtained by heel stick and analysed by isoelectric focusing
      as a first-line method, followed by either high-performance liquid chromatography
      or acid agar electrophoresis for confirmation, whenever a variant haemoglobin is
      observed on isoelectric focusing. RESULTS: In 2007, 28.45% of all newborns in
      mainland France were screened for SCD. Since 1996, a total of 3,890 newborns have
      been found to have SCD, and they have been followed up by reference
      paediatricians. CONCLUSION: Although screening for SCD at birth in France is not
      universal, it appears that missed babies are relatively infrequent. Despite
      obvious sociological problems inherent to the at-risk population, the follow-up
      of SCD babies is rather successful. Due to the birth prevalence of SCD in France,
      especially in comparison with other common genetic diseases, screening all
      newborns regardless of ethnic origin is an issue that is being addressed.

PMID- 19103856
TI  - Haemoglobinopathies and newborn haemoglobinopathy screening in Germany.
AB  - Germany has been an immigration country since the early 1950s. In December 2007,
      6.7 million non-German citizens lived in the country. However, the total number
      of citizens with a migration background is 15-20 million, about 9 million of whom
      come from countries where sickle cell disease and thalassaemias are frequent. In
      a country with 82 million inhabitants health authorities are not worried by the
      presence of probably 1000-1500 sickle cell and 450 transfusion-dependent
      thalassaemia patients, and therefore no screening or preventive measures have
      been taken so far on a national scale. There are plans for a pilot project (1
      year) to screen all newborns for sickle cell disease in obstetric hospitals in 4
      5 cities with more than 20% migrants. Funding and lack of an infrastructure to
      provide counselling are major problems.

PMID- 19103857
TI  - Neonatal screening for sickle cell anaemia in the Democratic Republic of the
      Congo: experience from a pioneer project on 31 204 newborns.
AB  - BACKGROUND: Despite the high prevalence of sickle cell disease in Africa, a
      neonatal screening programme is available in only a few countries in the sub
      Saharan region. AIM: To describe our experience of a pioneer study on 31,304
      newborns screened systematically in the Democratic Republic of the Congo.
      METHODS: The prevalence of haemoglobinopathies was determined by a thin-layer
      isoelectric focusing method on dry filter-paper samples. RESULTS: Of the 31,204
      newborns screened by isoelectric focusing, 5,276 (16.9%) displayed sickle cell
      trait and 428 (1.4%) were homozygous for haemoglobin S. No statistical
      differences were observed in the different ethno-linguistic groups, but some
      tribes displayed a higher prevalence of the betaS gene, attributable to a higher
      prevalence of malaria, and a greater frequency of haemoglobin S homozygotes, in
      part attributable to an endogamic marriage system. CONCLUSION: The neonatal
      screening programme has now been introduced in the Democratic Republic of the
      Congo, but the main challenges are to track all the new cases for a confirmatory
      test and to initiate early management.

PMID- 19103858
TI  - Neonatal haemoglobinopathy screening in Burkina Faso.
AB  - AIMS: To report our experience of neonatal screening for sickle cell disease in
      Ouagadougou (Burkina Faso) and to discuss the feasibility of neonatal screening
      in this country. METHODS: Between the years 2000 and 2004, there were about 2,341
      births in five maternity services in Ouagadougou. These babies were screened for
      sickle cell disease in a universal screening pilot programme. In 2006, 53 babies
      born to selected couples were screened. The specimens were collected either by
      cord blood sampling or from a dried blood spot on filter paper. The screening was
      performed using an isoelectric focusing technique. RESULTS: In the first stage
      (2000-4), the incidence of sickle cell disease was 1:57. In the second stage, six
      of 53 babies of selected couples were found to have major haemoglobinopathies:
      one was homozygous for haemoglobin S and five were compound heterozygotes for
      haemoglobins S and C. CONCLUSIONS: The results suggest that a national screening
      programme should be implemented in Burkina Faso with effective newborn and
      subsequent follow-up, but a methodology needs to be developed.

PMID- 19103859
TI  - An audit of immunisation status of sickle cell patients in Coventry, UK.
AB  - Protection against infection is a key aim of any care programme for patients with
      sickle cell disorders, and is one of the stated objectives of the UK national
      neonatal screening programme. An audit of the immunisation status of the 58
      sickle cell patients living in Coventry was carried out against UK national
      guidance (2006). Among 25 children (aged < or =16 years), 14 (56%) had complete
      immunisation against pneumococcus, Haemophilus influenzae type b (Hib) and
      meningococcus group C (MenC), with eight (32%) having some coverage, and three
      (12%) having none at all. Among 33 adults, only four patients (12%) had complete
      coverage, with up-to-date coverage against pneumococcus 21%, Hib 18% and MenC
      15%. Current (ie, within the last year) immunisation against viral influenza was
      found in only 12% of adults and 8% of children. These rates are similar to those
      found in other UK studies. If the potential benefits of neonatal screening are to
      be realised, an effective immunisation programme is essential. There are key
      roles for haemoglobinopathy nurse specialists, and the proposed national
      haemoglobinopathy database, in improving the rates of immunisation coverage.

PMID- 19103860
TI  - Newborn screening for sickle cell disease in the Republic of Benin.
AB  - AIMS: To develop a strategy for neonatal screening of sickle cell disease (SCD)
      and effective enrollment of affected neonates in a comprehensive follow-up
      programme adapted to the socioeconomic conditions, health structures and cultural
      background of an African setting. METHODS: The strategy implemented at the two
      largest maternity services of Cotonou, the economic capital of the Republic of
      Benin, involves a team of specifically trained midwives, first to identify
      pregnant women at risk, and second to provide active and repeated information and
      sensitisation to these women to encourage voluntary demand for newborn screening
      and enrollment in the follow-up programme. RESULTS: Among the consecutive
      pregnant women studied (about 3000), 79.5% of the informed women at risk for
      fetal SCD asked for testing of their offspring, 85.2% of the newborns who tested
      positive were enrolled in the programme, and more than 80% were still being
      followed up after 5 years. The under-five mortality rate in this series was 15.5
      per 10,000, a figure that is 10 times lower than the general rate recorded in the
      Republic of Benin. CONCLUSIONS: The results demonstrate that this specifically
      tailored strategy is relevant to this setting, given the unique conditions of
      this African country.

PMID- 19103861
TI  - Neonatal haemoglobinopathy screening in Belgium.
AB  - BACKGROUND: A neonatal haemoglobinopathy screening programme was implemented in
      Brussels more than a decade ago and in Liege 5 years ago; the programme was
      adapted to the local situation. METHODS: Neonatal screening for
      haemoglobinopathies was universal, performed using liquid cord blood and an
      isoelectric focusing technique. All samples with abnormalities underwent
      confirmatory testing. Major and minor haemoglobinopathies were reported. Affected
      children were referred to a specialist centre. A central database in which all
      screening results were stored was available and accessible to local care workers.
      A central clinical database to monitor follow-up is under construction. RESULTS:
      A total of 191,783 newborns were screened. One hundred and twenty-three (1:1559)
      newborns were diagnosed with sickle cell disease, seven (1:27,398) with beta
      thalassaemia major, five (1:38,357) with haemoglobin H disease, and seven
      (1:27,398) with haemoglobin C disease. All major haemoglobinopathies were
      confirmed, and follow-up of the infants was undertaken except for three infants
      who did not attend the first medical consultation despite all efforts.
      CONCLUSIONS: The universal neonatal screening programme was effective because no
      case of major haemoglobinopathy was identified after the neonatal period. The
      affected children received dedicated medical care from birth. The screening
      programme, and specifically the reporting of minor haemoglobinopathies, has been
      an excellent health education tool in Belgium for more than 12 years.

PMID- 19103862
TI  - Neonatal/newborn haemoglobinopathy screening in Europe and Africa.
AB  - Neonatal/newborn haemoglobinopathy screening is being performed in an increasing
      number of European countries since changing patterns of immigration have led to
      significant numbers of neonates at risk of sickle cell disease. The purpose of
      screening is to improve management of sickle cell disease through early parental
      education and the institution of prophylaxis against infection. Some
      haemoglobinopathy screening programmes are stand-alone, while others are
      integrated into a neonatal screening programme for metabolic disorders. Despite
      the logistic problems and economic constraints, neonatal haemoglobinopathy
      screening is also being gradually introduced in a number of African countries.

PMID- 19103863
TI  - The copper/caeruloplasmin ratio in routine clinical practice in different
      laboratories.
AB  - BACKGROUND: The diagnosis of copper deficiency and excess states is challenging.
      It was hoped that the non-caeruloplasmin-bound ("free") copper would reduce this
      difficulty; however, it has its own problems. The copper/caeruloplasmin ratio has
      been advocated as an alternative index of copper status, especially as it would
      not need gender-derived or age-derived reference intervals. However, there are no
      comparative data for different populations using different assays. METHOD:
      Independent paired copper and caeruloplasmin data were retrospectively obtained
      for three laboratories. From these data, the copper/caeruloplasmin ratio was
      calculated, and descriptive statistics for the populations and methods were
      obtained. The relationship between the copper/caeruloplasmin ratio and both
      copper and caeruloplasmin were also investigated for the three laboratories.
      RESULTS: All three datasets displayed a non-Gaussian distribution. The Burton
      median was statistically different from the two other medians, which did not
      differ significantly from each other. The regression lines for both copper and
      caeruloplasmin with the ratio differed from each other. CONCLUSION: The
      copper/caeruloplasmin ratio behaves differently depending on the laboratory, the
      population studied, or both. Thus, cut-offs in the literature are not
      transferable. Each laboratory should therefore derive its own cut-offs.

PMID- 19103864
TI  - Clinical impact of enhanced diagnosis of invasive fungal disease in high-risk
      haematology and stem cell transplant patients.
AB  - AIMS: To investigate the impact of routine use of biomarkers for diagnosing
      fungal infection within a care pathway on antifungal usage and clinical outcomes.
      METHODS: A cohort of high-risk haematology and stem cell transplant patients was
      entered into a neutropenic care pathway in which targeted diagnostic testing
      replaced empiric antifungal treatment. Patients were screened twice a week by PCR
      and antigen testing during fever or when chronic graft versus host disease was
      present and were followed-up for a minimum of 1 year. RESULTS: No excess
      morbidity or mortality was seen in patients in whom empiric antifungal treatment
      was withheld, and there were substantial savings in antifungal drug expenditure.
      CONCLUSIONS: The introduction of a comprehensive diagnostic surveillance strategy
      to exclude invasive fungal infection in high-risk patients with haematological
      malignancy and those undergoing transplantation can result in improvements in
      clinical management. There are also potential additional benefits of improved
      patient survival, decreased morbidity and decreased hospital stay.

PMID- 19103865
TI  - p63 protein expression in high risk diffuse large B-cell lymphoma.
AB  - BACKGROUND: p63 gene is a p53 homologue that encodes proteins with
      transactivation, DNA-binding and tetramerisation domains. The isoforms TAp63 and
      TAp73 transactivate p53 target genes and induce apoptosis, whereas the isoforms
      DeltaNp63 and DeltaNp73 lack transactivation and might have dominant-negative
      effects in p53 family members. p63 is expressed in germinal centre lymphocytes
      and can be related to the development of the lymphoma, but the prognostic
      significance of its expression in the survival of patients with diffuse large B
      cell lymphoma (DLBCL) remains unclear. AIMS: To determine whether quantitative
      immunohistochemical (IHC) analysis of p63 protein expression correlates with CD10
      antigen, Bcl-6 antigen and IRF4 antigen expression and to determine whether p63
      is a surrogate predictor of overall survival in high-intermediate and high risk
      DLBCL populations. METHODS: CD10, Bcl-6 and IRF4 expression were retrospectively
      evaluated by IHC in 73 samples of high-intermediate and high risk DLBCL and were
      used to divide the lymphomas into subgroups of germinal centre B-cell-like (GCB)
      and activate B-cell-like (ABC) DLBCL. Similarly, p63 expression was evaluated by
      IHC and the results were compared with subgroups of DLBCL origin and with the
      survival rates for these patients. RESULTS: p63 was expressed in more than 50% of
      malignant cells in 11 patients and did not show correlation with subgroups of GCB
      like DLBCL or ABC-like DLBCL, but p63(+) patients had better disease-free
      survival (DFS) than those who were negative (p = 0.01). CONCLUSIONS: p63(+) high
      intermediate and high risk DLBCL patients have a better DFS than negative cases.

PMID- 19103866
TI  - Multifocal primary extranodal B-cell non-Hodgkin's lymphoma involving six
      extranodal sites.
AB  - An unusual case of Epstein-Barr virus-negative primary extranodal B-cell non
      Hodgkin's lymphoma involving six anatomical sites is described in a report that
      challenges the role of organotropism in the pathogenesis of extranodal lymphoma.

PMID- 19103868
TI  - The oestrogen receptor-negative/progesterone receptor-positive breast tumour: a
      biological entity or a technical artefact?

PMID- 19103869
TI  - Tyrosine-rich crystalloids in vocal cord mucosa.

PMID- 19103870
TI  - Smoke and dust get in your eyes: what does it mean in the workplace?

PMID- 19103871
TI  - Beyond airflow limitation: another look at COPD.

PMID- 19103872
TI  - Statins for the treatment of asthma: a discovery well, dry hole or just snake
      oil.

PMID- 19103873
TI  - An unusual cause of patchy ground-glass opacity.

PMID- 19103874
TI  - Neutrophils in cystic fibrosis.
AB  - Lung injury in cystic fibrosis is caused by recurrent airway infection and
      inflammation. Neutrophils are important in combating these infections but are
      also the predominate cells involved in the inflammatory process. This review of
      neutrophils in cystic fibrosis describes the cellular mechanisms involved in
      their migration into the airways and their role in bacterial phagocytosis. We
      discuss the inflammatory process and its resolution and ultimately how neutrophil
      function can be modulated.

PMID- 19103875
TI  - Human and canine pulmonary Mycobacterium bovis infection in the same household:
      re-emergence of an old zoonotic threat?
AB  - Bovine tuberculosis (bTB), caused by Mycobacterium bovis, remains a serious
      animal health problem in the UK, despite longstanding statutory surveillance and
      control measures. Endemic infection in the Eurasian badger population is thought
      to complicate bTB eradication efforts. Sporadic cases of M bovis infection have
      also been reported in domestic animals other than cattle. Human M bovis infection
      is extremely rare in the native UK population in the absence of unpasteurised
      milk consumption or residence abroad. Here, pulmonary TB infection in a UK born
      female and her pet dog is described, caused by an identical strain of M bovis.
      Latent TB infection was also identified in a household contact. The potential
      routes of infection and implications of this case are discussed.

PMID- 19103876
TI  - 99mTechnetium-labelled neutrophil scanning in pneumonia.

PMID- 19103877
TI  - IL-15 trans-presentation promotes human NK cell development and differentiation
      in vivo.
AB  - The in vivo requirements for human natural killer (NK) cell development and
      differentiation into cytotoxic effectors expressing inhibitory receptors for self
      major histocompatibility complex class I (MHC-I; killer Ig-like receptors [KIRs])
      remain undefined. Here, we dissect the role of interleukin (IL)-15 in human NK
      cell development using Rag2(-/-)gamma c(-/-) mice transplanted with human
      hematopoietic stem cells. Human NK cell reconstitution was intrinsically low in
      this model because of the poor reactivity to mouse IL-15. Although exogenous
      human IL-15 (hIL-15) alone made little improvement, IL-15 coupled to IL-15
      receptor alpha (IL-15R alpha) significantly augmented human NK cells. IL-15-IL
      15R alpha complexes induced extensive NK cell proliferation and differentiation,
      resulting in accumulation of CD16(+)KIR(+) NK cells, which was not uniquely
      dependent on enhanced survival or preferential responsiveness of this subset to
      IL-15. Human NK cell differentiation in vivo required hIL-15 and progressed in a
      linear fashion from CD56(hi)CD16(-)KIR(-) to CD56(lo)CD16(+)KIR(-), and finally
      to CD56(lo)CD16(+)KIR(+). These data provide the first evidence that IL-15 trans
      presentation regulates human NK cell homeostasis. Use of hIL-15 receptor agonists
      generates a robust humanized immune system model to study human NK cells in vivo.
      IL-15 receptor agonists may provide therapeutic tools to improve NK cell
      reconstitution after bone marrow transplants, enhance graft versus leukemia
      effects, and increase the pool of IL-15-responsive cells during immunotherapy
      strategies.

PMID- 19103878
TI  - Functional anergy in a subpopulation of naive B cells from healthy humans that
      express autoreactive immunoglobulin receptors.
AB  - Self-reactive B cells not controlled by receptor editing or clonal deletion may
      become anergic. We report that fully mature human B cells negative for surface
      IgM and retaining only IgD are autoreactive and functionally attenuated (referred
      to as naive IgD(+)IgM(-) B cells [B(ND)]). These B(ND) cells typically make up
      2.5% of B cells in the peripheral blood, have antibody variable region genes in
      germline (unmutated) configuration, and, by all current measures, are fully
      mature. Analysis of 95 recombinant antibodies expressed from the variable genes
      of single B(ND) cells demonstrated that they are predominantly autoreactive,
      binding to HEp-2 cell antigens and DNA. Upon B cell receptor cross-linkage, B(ND)
      cells have a reduced capacity to mobilize intracellular calcium or phosphorylate
      tyrosines, demonstrating that they are anergic. However, intense stimulation
      causes B(ND) cells to fully respond, suggesting that these cells could be the
      precursors of autoantibody secreting plasma cells in autoimmune diseases such as
      systemic lupus erythematosus or rheumatoid arthritis. This is the first
      identification of a distinct mature human B cell subset that is naturally
      autoreactive and controlled by the tolerizing mechanism of functional anergy.

PMID- 19103879
TI  - Absence of SPARC results in increased cardiac rupture and dysfunction after acute
      myocardial infarction.
AB  - The matricellular protein SPARC (secreted protein, acidic and rich in cysteine,
      also known as osteonectin) mediates cell-matrix interactions during wound healing
      and regulates the production and/or assembly of the extracellular matrix (ECM).
      This study investigated whether SPARC functions in infarct healing and ECM
      maturation after myocardial infarction (MI). In comparison with wild-type (WT)
      mice, animals with a targeted inactivation of SPARC exhibited a fourfold increase
      in mortality that resulted from an increased incidence of cardiac rupture and
      failure after MI. SPARC-null infarcts had a disorganized granulation tissue and
      immature collagenous ECM. In contrast, adenoviral overexpression of SPARC in WT
      mice improved the collagen maturation and prevented cardiac dilatation and
      dysfunction after MI. In cardiac fibroblasts in vitro, reduction of SPARC by
      short hairpin RNA attenuated transforming growth factor beta (TGF)-mediated
      increase of Smad2 phosphorylation, whereas addition of recombinant SPARC
      increased Smad2 phosphorylation concordant with increased Smad2 phosphorylation
      in SPARC-treated mice. Importantly, infusion of TGF-beta rescued cardiac rupture
      in SPARC-null mice but did not significantly alter infarct healing in WT mice.
      These findings indicate that local production of SPARC is essential for
      maintenance of the integrity of cardiac ECM after MI. The protective effects of
      SPARC emphasize the potential therapeutic applications of this protein to prevent
      cardiac dilatation and dysfunction after MI.

PMID- 19103880
TI  - B cell antigen receptor signal strength and peripheral B cell development are
      regulated by a 9-O-acetyl sialic acid esterase.
AB  - We show that the enzymatic acetylation and deacetylation of a cell surface
      carbohydrate controls B cell development, signaling, and immunological tolerance.
      Mice with a mutation in sialate:O-acetyl esterase, an enzyme that specifically
      removes acetyl moieties from the 9-OH position of alpha2-6-linked sialic acid,
      exhibit enhanced B cell receptor (BCR) activation, defects in peripheral B cell
      development, and spontaneously develop antichromatin autoantibodies and
      glomerular immune complex deposits. The 9-O-acetylation state of sialic acid
      regulates the function of CD22, a Siglec that functions in vivo as an inhibitor
      of BCR signaling. These results describe a novel catalytic regulator of B cell
      signaling and underscore the crucial role of inhibitory signaling in the
      maintenance of immunological tolerance in the B lineage.

PMID- 19103882
TI  - Lei Wang: expanding the language of life. Interview by Kira O'Day.

PMID- 19103881
TI  - Maresins: novel macrophage mediators with potent antiinflammatory and
      proresolving actions.
AB  - The endogenous cellular and molecular mechanisms that control acute inflammation
      and its resolution are of wide interest. Using self-resolving inflammatory
      exudates and lipidomics, we have identified a new pathway involving biosynthesis
      of potent antiinflammatory and proresolving mediators from the essential fatty
      acid docosahexaenoic acid (DHA) by macrophages (MPhis). During the resolution of
      mouse peritonitis, exudates accumulated both 17-hydroxydocosahexaenoic acid, a
      known marker of 17S-D series resolvin (Rv) and protectin biosynthesis, and 14S
      hydroxydocosa-4Z,7Z,10Z,12E,16Z,19Z-hexaenoic acid from endogenous DHA. Addition
      of either DHA or 14S-hydroperoxydocosa-4Z,7Z,10Z,12E,16Z,19Z-hexaenoic acid to
      activated MPhis converted these substrates to novel dihydroxy-containing products
      that possessed potent antiinflammatory and proresolving activity with a potency
      similar to resolvin E1, 5S,12R,18R-trihydroxyeicosa-6Z,8E,10E,14Z,16E-pentaenoic
      acid, and protectin D1, 10R,17S-dihydroxydocosa-4Z,7Z,11E,13E,15Z,19Z-hexaenoic
      acid. Stable isotope incorporation, intermediate trapping, and characterization
      of physical and biological properties of the products demonstrated a novel 14
      lipoxygenase pathway, generating bioactive 7,14-dihydroxydocosa
      4Z,8,10,12,16Z,19Z-hexaenoic acid, coined MPhi mediator in resolving inflammation
      (maresin), which enhances resolution. These findings suggest that maresins and
      this new metabolome may be involved in some of the beneficial actions of DHA and
      MPhis in tissue homeostasis, inflammation resolution, wound healing, and host
      defense.

PMID- 19103883
TI  - How does HIV impact on non-AIDS events in the era of HAART?
AB  - Death rates from AIDS-related events in HIV-positive individuals have declined in
      the era of highly active antiretroviral therapy (HAART). It has also been shown
      that deaths from non-AIDS events have declined in this cohort since the advent of
      HAART. We review these data, as well as discussing some of the possible effects
      HAART might have on non-AIDS diagnoses and deaths in HIV-positive individuals
      with successfully treated HIV.

PMID- 19103884
TI  - Web-based forums for clients of female sex workers: development of a German
      internet approach to HIV/STD-related sexual safety.
AB  - Clients of sex workers in Germany used to be unapproachable for issues of sexual
      health. Thus, prevention of HIV and sexually transmitted diseases used to focus
      on sex workers only, even though many sex workers accuse clients preferring
      unprotected sex. When prostitution was decriminalized in Germany in 2002, a till
      then unknown platform emerged on the German internet. Clients set up forums for
      themselves and their peers. These community forums were primarily meant to serve
      as platforms for the exchange of information, e.g. on the quality of services. We
      describe the development and expansion of these web-sites for clients of female
      commercial sex workers, and the clientele and operation of such sites. To study
      and to describe the sites, a close cooperation with their webmasters and
      administrators was crucial. The clients' community forums mark a change in
      paradigm, as clients became an accessible and addressable target group for sexual
      health and prevention issues on the internet. The Sexsicher sites have been
      developed to adequately target this group.

PMID- 19103885
TI  - Condom use in the year following a sexually transmitted disease clinic visit.
AB  - Consistent condom use can prevent sexually transmitted infections (STIs), but few
      studies have measured how the prevalence of consistent use changes over time. We
      measured the prevalence and correlates of consistent condom use over the course
      of a year. We did a secondary analysis of data from an HIV prevention trial in
      three sexually transmitted disease clinics. We assessed condom use during four
      three-month intervals for subjects and across their partnerships using
      unconditional logistic regression. Condom use was also assessed for subjects
      during all three-month intervals combined. The 2125 subjects reported on 5364
      three-month intervals including 7249 partnership intervals. Condoms were always
      used by 24.1% of subjects and 33.2% of partnerships during a three-month
      interval. Over the year, 82% used condoms at least once but only 5.1% always used
      condoms. Always use of condom was more likely for subjects who had sex only once
      (66.5%) compared with >30 times (6.4%); one-time partnerships (64.1%) compared
      with main partnerships (22.2%); and in new partnerships (44.0%) compared with
      partnerships that were not new (24.5%). Although consistent condom use may
      prevent STIs, condoms were rarely used consistently during the year of follow-up.

PMID- 19103886
TI  - Non-consultant career grade doctors in genitourinary medicine - are they up to
      the job? National survey 2007.
AB  - Non-consultant career grade doctors in genitourinary (GU) medicine have been
      called 'a reliable silent backbone of the specialty' and 'a spare pair of hands'
      [Hiscock E. Non-consultant career grade staff in GU medicine; a reliable backbone
      or, a spare pair of hands? Int J STD AIDS 1996;7:375-7]. But are they adequate
      pairs of hands? This survey, conducted in July 2007, examined the work,
      qualifications and experience of these doctors. A summary of the 154 (19%)
      responses is presented. Respondents contributed 773 sessions per week, including
      164 special interest sessions; 30 (19.5%) were doing regular HIV work. Non
      clinical work was described by 134 (87%), especially teaching (132 [86%]) and
      management roles (26 [17%]). Postgraduate qualifications were cited by 148 (96%),
      including DipGUM or Dip Ven (51 [33%]), contraception qualifications such as
      DFFP, MFFP or FFFP (110 [71%]), MRCGP (43 [8%]) and qualifications in
      psychosexual medicine/therapy (10 [6.5%]). Over half were trained in general
      practice. Certificate of completion of specialist training or equivalent was held
      by 55 (36%), including two in GU medicine. These doctors are well qualified, and
      an asset to the specialty.

PMID- 19103887
TI  - Treatment of asymptomatic rectal Chlamydia trachomatis: is single-dose
      azithromycin effective?
AB  - Rectal infection with Chlamydia trachomatis affects approximately 7% of men
      having sex with men (MSM), attending departments of Genito-Urinary (GU) Medicine
      [Manavi et al. Int J STD AIDS 2004;15:162-4], and the British Association for
      Sexual Health and HIV (BASHH) guidelines for the treatment of uncomplicated
      genital C. trachomatis infection include 1 g of single-dose oral azithromycin as
      a recommended regimen [BASHH 2006]. A retrospective analysis was performed on
      case-notes from all patients diagnosed with rectal C. trachomatis infection in
      the department of GU Medicine, Edinburgh for the one-year period from 1 June
      2005. Of 101 new episodes of rectal chlamydial infection, only 9% were associated
      with anorectal symptoms. Excluding these, 85% of asymptomatic patients were
      treated with a single dose of azithromycin 1 g orally, with a calculated
      treatment failure rate of 13% (nine of 68). This suggests that single-dose
      azithromycin may be a less than effective treatment in asymptomatic rectal C.
      trachomatis infection. The potential treatment failure rate with this regimen
      emphasizes the need for a test of cure at the appropriate interval following
      treatment to ensure clearance of infection.

PMID- 19103888
TI  - Exploratory study of blood exposures that are risks for HIV among Luo and Kisii
      ethnic groups in Nyanza province, Kenya.
AB  - Adult HIV prevalence exceeds 5% among all Kenyans, and 20% among the Luo ethnic
      group. Recent studies have associated HIV infections in Kenya with several
      invasive health care and cosmetic procedures. To explore the various blood
      exposures that could contribute to HIV infections in Kenya, we surveyed 320
      adolescents and adults aged 15-29 years from the Luo and Kisii ethnic groups.
      Survey participants reported a wide range of invasive procedures in health care
      (including circumcisions, dental care, blood tests, and 1-60 injections or
      infusions for specific health problems), in cosmetic services (including
      tattooing and piercing) and around the home (through shaving body hair, fights,
      sports and other activities). Luo were significantly more likely than Kisii to
      report some risks (e.g. tattooing by a traditional expert, piercing), but less
      likely to report others (e.g. blood tests for malaria, anaesthetic injections
      during circumcision).

PMID- 19103889
TI  - A trial of the validity of genital smears and cultures with gonococcal vaccine
      provocation in diagnosing genital gonorrhoea in women.
AB  - In Russia the diagnosis of gonorrhoea in women relied on microscopy, justified by
      the hypothesis that sensitivity increases using 'provocation' techniques. The aim
      was to test the value of Gonovaccine as provocation in women who would have
      received it normally. Cervical specimens from 204 women were tested by culture
      and a ligase chain reaction (LCR) assay before the women were randomized to
      receive provocation or not. Further cervical specimens were obtained 24, 48 and
      72 hours later for microscopy, culture and LCR tests. In both provocation and non
      provocation arms, 24 women were positive for gonorrhoea by the LCR assay. Test-by
      test, sensitivity of microscopy was 30% in the provocation arm and 13% in the
      control arm (P = 0.0407, Fisher's exact test). Patient-by-patient, sensitivity of
      microscopy was 50% in the provocation arm, but only 25% in the control arm (P =
      0.0675, Fisher's exact test). The cost per case was greater ($214) using
      provocation with microscopy than culture and microscopy at the first visit
      ($150). Thus, although Gonovaccine provocation doubled the sensitivity of
      microscopy in detecting gonococci, the internationally recommended protocol of
      microscopy and culture at first visit should be adopted as routine practice in
      Russia. The findings raise questions about the pathogenesis and natural history
      of gonorrhoea.

PMID- 19103890
TI  - Can a clinical prediction tool guide HIV-testing decisions? Experience at a
      national hospital in Guatemala.
AB  - The USA and international recommendations no longer emphasize using risk factors
      to target groups for HIV-testing. Using a Guatemalan database of HIV tests, we
      developed a clinical prediction rule to guide decisions on HIV-testing. Prior to
      HIV-testing, data were collected on demographics, risk factors and prior testing.
      Based on a theoretical construct incorporating demographics, known HIV risk
      factors and symptoms, we developed a logistic regression model to predict HIV
      seropositivity. Between 2000 and 2005, 16,471 tests were performed, of which
      19.8% were positive. The algorithm successfully predicted 1883 of 2489 HIV
      positive tests (sensitivity 76%, likelihood ratio [LR]-positive 2.45) and 6282 of
      9086 HIV-negative tests (specificity 69%, LR-negative 0.35). Although the model
      indices are robust, applying the model in a clinical setting would have little
      impact on improving selective testing practices. Our findings support current
      recommendations for universal HIV-testing, not selective testing based on risk
      factors. Before these recommendations can be adopted widely in Guatemala,
      treatment access needs to be assured and protections put in place for people
      diagnosed with HIV infection.

PMID- 19103891
TI  - Agreement in self-reported personal risk factor information collected by
      different modes in Mongolia.
AB  - This study compares two methods (a self-administered paper survey and a face-to
      face interview) of collecting information about personal risk behaviours
      important for studies of HIV and other blood-borne pathogen transmissions in a
      developing country. In the framework of an epidemiological study conducted among
      2504 donors in the Blood Center at the Ministry of Health, Mongolia, 2250
      participants completed a short paper survey and 923 participants were interviewed
      concerning risk factors for hepatitis infections. A total of 669 individuals
      completed both surveys. McNemar's test and Kappa statistics were used to compare
      responses from both types of questionnaire. Kappa coefficients for health-care
      factors ranged from 0.57 (injection outside of hospital) to 0.81 (previous blood
      donation). Alcohol use and smoking were both reported more often in the interview
      than in the survey; the kappa coefficient was lowest (0.61) for alcohol use.
      While the prevalence of these behaviours depended on the mode of data collection,
      the association between behaviour and an outcome, hepatitis B surface antigen,
      was not substantially different between the two data collection methods. The
      results indicate that misclassification of risk behaviours is likely regardless
      of data collection method. However, in this study we found that biased estimates
      of prevalence likely did not substantially bias the estimates of association
      between risk factors and blood-borne infection.

PMID- 19103892
TI  - General hygiene, sexual risk behaviour and HIV prevalence in truck drivers from
      Andhra Pradesh, South India: implications for prevention interventions.
AB  - The relationships between hygiene, sexual behaviour and HIV infection are poorly
      understood. We examine these relationships in Indian truck drivers, a group at
      high risk for HIV infection. Truck drivers (n = 189) were recruited into an
      integrated HIV and hygiene Information Motivation (IM) programme.
      Sociodemographic characteristics, sexual and hygiene behaviour and HIV prevalence
      were determined. Multivariate logistic regression and linear generalized
      estimating equation models were utilized. At baseline, 2.1% of drivers were HIV
      infected and 34% who reported having contact with female sex workers (FSWs) had
      contact within the previous six months. Those who washed their hands
      postdefecation were less likely to report genital symptoms (OR 0.02; P = 0.01)
      and have sex with an FSW (OR [odds ratio] 0.21; P = 0.05). After an IM
      intervention, there were no changes in sexual risk-taking behaviour (coefficient 
      0.15 to -0.02; P = 0.13-0.75); however, hygiene behaviour improved from baseline
      (coefficient 0.09-0.31; P < 0.01 to P = 0.03). Personal hygiene habits, like
      handwashing, seem to be a modifiable behaviour after a modest intervention,
      whereas HIV risk-taking behaviour was not. The association between hygiene and
      HIV risk-taking suggests the need for further evaluation of the relationship and
      that of other hygiene practices in high-risk men in India.

PMID- 19103893
TI  - Cost-effectiveness of voluntary HIV screening in Russia.
AB  - Russia has one of the world's fastest growing HIV epidemics, and HIV screening
      has been widespread. Whether such screening is an effective use of resources is
      unclear. We used epidemiologic and economic data from Russia to develop a Markov
      model to estimate costs, quality of life and survival associated with a voluntary
      HIV screening programme compared with no screening in Russia. We measured
      discounted lifetime health-care costs and quality-adjusted life years (QALYs)
      gained. We varied our inputs in sensitivity analysis. Early identification of HIV
      through screening provided a substantial benefit to persons with HIV, increasing
      life expectancy by 2.1 years and 1.7 QALYs. At a base-case prevalence of 1.2%,
      once-per-lifetime screening cost $13,396 per QALY gained, exclusive of benefit
      from reduced transmission. Cost-effectiveness of screening remained favourable
      until prevalence dropped below 0.04%. When HIV-transmission-related costs and
      benefits were included, once-per-lifetime screening cost $6910 per QALY gained
      and screening every two years cost $27,696 per QALY gained. An important
      determinant of the cost-effectiveness of screening was effectiveness of
      counselling about risk reduction. Early identification of HIV infection through
      screening in Russia is effective and cost-effective in all but the lowest
      prevalence groups.

PMID- 19103894
TI  - Delay in the diagnosis of early syphilis among men who have sex with men: need
      for greater community and health provider education.
AB  - The objective of this study was to determine the duration between onset of
      symptoms of early symptomatic syphilis and diagnosis among men who have sex with
      men (MSM). A review of cases of primary and secondary syphilis among MSM
      presented to the Melbourne Sexual Health Centre between January 2003 and August
      2007. The mean age of the 123 MSM included was 37 years. Fifty-two percent (n =
      64) presented with primary syphilis and 48% (n = 59) with secondary syphilis.
      Twenty-five percent were HIV-positive. The median rapid plasma reagin titre was
      1:32. Of the 34 men referred by general practitioners, referring practitioners
      did not consider the diagnosis of syphilis in 10 cases of primary syphilis and 20
      cases of secondary syphilis. For primary and secondary cases combined, the median
      duration between onset of symptoms and diagnosis, and onset of symptoms and
      treatment, was 15 (3-56) and 20 (1-57) days, respectively. The respective
      durations for secondary syphilis (17 and 23 days) was longer than for primary
      syphilis (13 and 15 days) (P < 0.05). The mean number of sex partners reported
      for the prior three months was 8.8 (range 1-15). If early detection and treatment
      of syphilis is to be optimized in order to improve syphilis control, greater
      awareness of its symptoms and signs of syphilis need to be promoted among both
      health-care providers and affected communities.

PMID- 19103895
TI  - Introduction of a nurse-led sexual health service for HIV-positive men.
AB  - A nurse-led clinic offering screening for sexual infections to men within an
      existing HIV outpatient service was created. A retrospective case-note review was
      undertaken of those having a sexual health (SH) screen between May and December
      2007. A total of 125 men had an SH screen, 117 identified as men who have sex
      with men and 84 were asymptomatic. Six (7%) asymptomatic men had chlamydial and
      two (2%) had gonococcal infection. Six new diagnoses of syphilis and two of
      hepatitis C virus infection were made. We suggest that introducing a nurse-led
      clinic offering SH screening within HIV services has helped to achieve national
      standards and improved the SH of our patients.

PMID- 19103896
TI  - HIV opt-out increases HIV testing in low-risk patients.
AB  - We audited the effect of introducing HIV opt-out in a genitourinary medicine
      clinic in central London, UK. We found that opt-out increased the rate at which
      HIV testing was offered to low-risk patients and that more tests were done.

PMID- 19103897
TI  - Anglian Genitourinary Medicine Audit Group -- cervical cytology screening in HIV
      positive women.
AB  - Immunosuppressed HIV-infected women are at risk of developing cervical
      cytological abnormalities and should have routine annual cervical cytology smears
      performed as recommended by the National Health Services Cervical Screening
      Programme (NHSCSP). In the Anglian Genitourinary Medicine Audit Group review of
      practice of cervical cytology smears, only 55.5% of clinics met the NHSCSP
      standards. The mean age of the 173 women in the cohort was 35.8 +/- 8.1, range 16
      66 years. Seventy-eight percent of clinics performed cervical cytology screening
      in women under the age of 25 years. High-grade cervical cytological abnormality
      (moderate dyskariosis and above) was seen in 9.5% of the cohort and 39.5% had low
      grade lesions (borderline and mild dyskariosis). One patient, a 41-year-old black
      African on highly active antiretroviral therapy with HIV-1 RNA level <50
      copies/mL and a CD4 count of 240 cells/mm(3) had invasive cervical cancer
      requiring hysterectomy. The expected mean number of cervical cytology smears for
      the cohort was 3.29 and the calculated performed mean cervical cytology smear was
      1.9 (P = 0.0001), a statistically significant difference. Asylum dispersal among
      69.5% black Africans in the cohort contributed to some of the clinics not meeting
      the NHSCSP standards.

PMID- 19103898
TI  - An unusual case of vulval lump: tumour of anogenital mammary-like glands.
AB  - We describe a 37-year-old woman who presented with a painless vulval lump of
      eight months duration. Excision biopsy revealed a benign lesion thought to be
      derived from mammary-like glands, which are well-documented in the anogenital
      region but under-recognized among genitourinary medicine practitioners. Our case
      highlights the importance of having a low threshold for biopsy of atypical vulval
      lesions.

PMID- 19103899
TI  - Chronic knee stiffness and swelling in a Zimbabwean adolescent.
AB  - A 12-year-old Zimbabwean girl presented with tuberculous monoarthritis. She was
      moderately wasted, stunted and sexually immature. These clinical findings lead to
      the diagnosis of underlying HIV infection, which was thought to have been
      acquired from mother-to-child transmission.

PMID- 19103900
TI  - Acute syphilitic interstitial orchitis mimicking testicular malignancy in an HIV
      1 infected man diagnosed by Treponema pallidum polymerase chain reaction.
AB  - We report a case of acute epididymo-orchitis due to early infectious syphilis,
      mimicking as testicular malignancy in an undiagnosed HIV-positive individual. He
      presented with a mass on his testicle and simultaneously had serology consistent
      with early syphilis. It could not be distinguished from a malignancy, which
      necessitated urgent orchidectomy. Histology showed endarteritis but no evidence
      of gummatous involvement. Although treponemes were not detected by staining, the
      diagnosis was confirmed by the first reported use of Treponema pallidum
      polymerase chain reaction in a testicular specimen in the UK.

PMID- 19103901
TI  - Can the stigma of sexually transmitted infections affect the reported route of
      transmission by patients from particular sociocultural groups?

PMID- 19103902
TI  - One-stop care for HIV-positive women.

PMID- 19103903
TI  - Persistent sexual dysfunction in genitourinary medicine clinic attendees induced
      by selective serotonin reuptake inhibitors.

PMID- 19103904
TI  - HSV-1 genital infection rare in men over the age of 35 years.

PMID- 19103905
TI  - The role of health care in the spread of HIV/AIDS in Africa: evidence from Kenya.

PMID- 19103906
TI  - The unhealthy attempts by CDC and WHO to deny the importance of HIV transmission
      through unsafe health care.

PMID- 19103907
TI  - Stopping HIV/AIDS - can China succeed?

PMID- 19103908
TI  - Can financial carrots improve health?

PMID- 19103909
TI  - Health services and climate change: what can be done?

PMID- 19103910
TI  - Audit of submissions: July 2007 to June 2008.

PMID- 19103911
TI  - The influence of professional values on the implementation of Aboriginal health
      policy.
AB  - OBJECTIVE: This article explores the role of professional values and the culture
      of the Australian health care system in facilitating and constraining the
      implementation of an Aboriginal health policy. METHODS: Thirty-five semi
      structured in-depth interviews were conducted in a case study on the
      implementation of the Northern Territory Preventable Chronic Disease Strategy
      (PCDS). RESULTS: PCDS included three major evidence-based components - primary
      prevention, early detection and better management. The research revealed that
      PCDS changed as it was implemented. The values of the medical and nursing
      professions favoured the implementation of the clinically-based component of PCDS
      - better management. But there was dissonance between the values of these
      dominant professional groups and the values and expertise in public health that
      were necessary to implement fully the primary prevention component of PCDS. While
      Aboriginal health workers have valuable knowledge and skills in this area, they
      were not accorded sufficient power and training to influence decision-making on
      priorities and resources, and were able to exercise only limited influence on the
      components of the PCDS that were implemented. CONCLUSION: The findings highlight
      the role that a myriad of values play in influencing which aspects of a policy
      are implemented by organizations and their agents. Comprehensive and equitable
      implementation of policy requires an investigation and awareness of different
      professional values, and an examination of whose voices will be privileged in the
      decision-making process. If the advances in developing evidence-based, culturally
      appropriate and inclusive policy are to be translated into practice, then care
      needs to be taken to monitor and influence whose values are being included at
      what point in the policy implementation process.

PMID- 19103912
TI  - Public attitudes to the storage of blood left over from routine general practice
      tests and its use in research.
AB  - OBJECTIVE: There is increasing international interest in DNA biobanks but
      relatively little evidence concerning appropriate recruitment methods for these
      repositories of genetic information linked to patient-specific phenotypic data.
      To this end, our study aimed to investigate the attitudes of members of the
      public recruited through general practices to the donation and storage of blood
      left over from routine clinical tests in general practice. METHODS: A
      questionnaire was mailed to 2600 individuals randomly selected from two general
      practice patient lists in Dundee, Scotland. Using a 7-point Likert scale,
      respondents rated their attitudes toward DNA biobanks in general, and procurement
      of blood samples specifically. RESULTS: Overall, 841 (34%) of 2471 delivered
      questionnaires were returned. Compared with patients on the practice lists,
      respondents were older and more likely to be women. A majority of respondents
      (61%) were unequivocally positive about storing blood left over from routine
      tests. Despite general support for this collection method, when asked about open
      ended consent, respondents expressed concern about future uses. Respondents'
      increasing age and level of deprivation had significant adverse effects on
      attitudes towards making leftover routine biological samples available for
      research (P = 0.013 and P = 0.034, respectively). The study had three main
      limitations: there was a low response rate (34%) such that respondents were not
      entirely respresentative of the survey population; some respondents had
      difficulty with the questionnaire; and the study was somewhat underpowered for
      some comparisons. CONCLUSION: Despite its limitations, this first survey of a
      general practice population suggests that the majority would be willing to
      consider giving open-ended consent for the use of blood left over from routine
      clinical tests in general practice to be stored and used later for medical
      research.

PMID- 19103913
TI  - 'We can't get anything done because...': making sense of 'barriers' to Practice
      based Commissioning.
AB  - OBJECTIVES: To investigate the issues raised by participants as 'barriers' to the
      development of Practice-based Commissioning (PBC) in 'early adopter' sites in
      England. METHODS: Detailed case studies of five PBC consortia in three Primary
      Care Trusts (PCTs). Data collection included interviews with a wide range of
      respondents (46 in total), including general practitioners, PCT employees, Local
      Authority employees and patient representatives, observation of many different
      types of meetings (68 in total), and analysis of documents tabled at meetings and
      circulated at other times. RESULTS: It has been claimed that progress in
      developing PBC has been slow. Our respondents articulated a number of factors
      that they felt were holding them back, which could have been identified as
      'barriers' preventing change. The issues raised were consistent across our sites
      (lack of time, resources and personnel, and difficult relationships with the
      PCT), but observation suggested that these issues arose out of very different
      organizational 'sensemaking', and as a result the apparent 'barriers' had
      different meanings in different organizational contexts. CONCLUSION: Weick's
      concept of 'organizational sensemaking' provides a useful framework within which
      to explore the problems encountered when implementing policy. Observational
      methods are a powerful tool in understanding sensemaking. The variations in
      sensemaking that we observed suggest that the use of 'barrier' metaphors in
      descriptions of implementation problems risks homogenizing the portrayal of
      situations that differ greatly in reality. This implies that top-down or
      centrally driven solutions to such situations will often be inappropriate.

PMID- 19103914
TI  - Is it feasible to pool funds for local children's services in England? Evidence
      from the national evaluation of children's trust pathfinders.
AB  - OBJECTIVES: To describe how funds were pooled or otherwise jointly managed by
      National Health Service (NHS) primary care trusts and local authorities in
      England. To compare expenditure on local children's services by health, education
      and social services. METHODS: We conducted a questionnaire survey of all 35
      children's trust pathfinders, six months after they were launched, with a follow
      up at 2.5 years. We also undertook an in-depth analysis of local authorities and
      primary care trusts, within eight pathfinder areas and three non-pathfinder
      areas, whereby we compared expenditure on children's services, interviewed
      managers and professionals and examined financial documents. RESULTS: Local
      authorities and NHS trusts coordinated expenditure in various ways, most commonly
      through informal agreements and aligning budgets but also by formally pooling
      budgets. The latter were usually for selected services such as child and
      adolescent mental health services, though four children's trusts pathfinders
      pooled (or aligned) their budgets for all children's services. Total expenditure
      per child was greatest for education, lowest for social services and intermediate
      for health. However, it was difficult to quantify education expenditure on
      children with health and social care needs, and health care expenditure on
      children. CONCLUSIONS: Sharing money for local children's services requires
      shared objectives, trust, and legal and accounting expertise. Several different
      mechanisms are permitted and many are feasible but programme budgeting for
      children's services could make them more effective.

PMID- 19103915
TI  - Are home sampling kits for sexually transmitted infections acceptable among men
      who have sex with men?
AB  - OBJECTIVE: There is an urgent need to increase opportunistic screening for
      sexually transmitted infections (STIs) in community settings, particularly for
      those who are at increased risk including men who have sex with men (MSM). The
      aim of this qualitative study was to explore whether home sampling kits (HSK) for
      multiple bacterial STIs are potentially acceptable among MSM and to identify any
      concerns regarding their use. This study was developed as part of a formative
      evaluation of HSKs. METHODS: Focus groups and one-to-one semi-structured
      interviews with MSM were conducted. Focus group participants (n = 20) were shown
      a variety of self-sampling materials and asked to discuss them. Individual
      interviewees (n = 24) had experience of the self-sampling techniques as part of a
      pilot clinical study. All data were digitally recorded and transcribed verbatim.
      Data were analysed using a framework analysis approach. RESULTS: The concept of a
      HSK was generally viewed as positive, with many benefits identified relating to
      increased access to testing, enhanced personal comfort and empowerment. Concerns
      about the accuracy of the test, delays in receiving the results, the possible
      lack of support and potential negative impact on 'others' were raised.
      CONCLUSION: The widespread acceptability of using HSKs for the diagnosis of STIs
      could have important public health impacts in terms of earlier diagnosis of
      asymptomatic infections and thus a decrease in the rate of onward transmission.
      In addition, HSKs could potentially optimize the use of genitourinary medicine
      services and facilitate patient choice.

PMID- 19103916
TI  - From quasi-market to market in the National Health Service in England: what does
      this mean for the purchasing of health services?
AB  - The purchasing function was first developed within the British National Health
      Service as part of a quasi-market introduced by a Conservative government in 1990
      and retained by the Labour government on coming to power in 1997. Since 2002
      further reforms in England have begun to transform the quasi-market into a 'real'
      market with greater diversity of supplier, including from the private sector, a
      payment regime designed to reward additional hospital activity and new rights for
      patients to choose their provider. Evidence from the quasi-market era suggests
      that the purchasing function made little significant impact on services for
      patients or shifts in the pattern of hospital provision. The new market reforms,
      in theory, provide an opportunity to overcome prior weaknesses in the purchasing
      function. As this market develops, we suggest that the purchasers should develop
      three new sets of skills and activities if they are to be effective: the
      identification of need and shaping of demand; shaping the structure of supply;
      and holding the market to account.

PMID- 19103917
TI  - Reconstructing continuity of care in mental health services: a multilevel
      conceptual framework.
AB  - Continuity of mental health care is a key issue in the organization and
      evaluation of services for patients with disabling chronic conditions. Over many
      years, health services researchers have been exploring the conceptual boundaries
      between continuity of care and other service characteristics. On the basis of
      papers published over the past decade, we argue that while conceptual consensus
      is growing, there is room to improve continuity measures, and the development of
      practical interventions is still at an early stage. There is growing consensus
      that continuity of care is a multidimensional concept. We identified four core
      elements: continuous care; care of an individual patient; cross-boundary care;
      and care recorded objectively. These elements help clarify conceptual boundaries,
      and incorporate measurement guidelines. With reference to these core elements, we
      define types of continuity of care, including informational continuity,
      management continuity, relational continuity and contact continuity. In order to
      improve continuity of care, better understanding is needed of the complex inter
      relationship of core elements and types of continuity. A multilevel perspective
      on continuity of care can guide research to develop and evaluate new
      interventions. Achieving continuity of care is hindered by the lack of standard
      measures and administrative data appropriate to assessing continuity. Account
      should be taken not only of the nature of the patient population, but also of
      local conditions. To address these topics and identify best practices, research
      should be multidisciplinary and take a comparative, naturalistic form.

PMID- 19103918
TI  - Non-adherence to medicines: not solved but solvable.
AB  - Non-adherence to medicines is common, with convincing evidence for adverse
      effects on patient health and costs to health systems. At least half of reported
      non-adherence is intentional. An extensive body of research suggests that, while
      patient characteristics may contribute to this behaviour, key influences are
      linked to beliefs and experiences of an illness and its medicines.
      Characteristics of the health system such as patient-practitioner relationships
      and access are also significant drivers. Inadvertent effects of some policies,
      such as co-payments, reduce adherence. Interventions to improve adherence have
      not utilized available research evidence fully and are not integrated into
      service delivery, so have been disappointing in producing sustained behaviour
      change. Policies relying on patients' adherence to medicines will not be as
      effective as hoped if adherence is assumed rather than supported. Substantial
      gains could be made by patients and health systems if patients, practitioners,
      researchers and policy-makers worked together to improve this crucial area of
      health behaviour.

PMID- 19103919
TI  - The membrane lipoprotein LppX of Paenibacillus sp. strain W-61 serves as a
      molecular chaperone for xylanase of glycoside hydrolase family 11 during
      secretion across the cytoplasmic membrane.
AB  - Paenibacillus sp. strain W-61, which can utilize xylan as the sole source of
      carbon and energy, produces extracellular xylanases 1 and 3 (Xyn1 and Xyn3) and
      cell surface xylanase 5. In this study we found that lppX, immediately downstream
      of xyn1, encodes a lipoprotein located on the outer layer of the cytoplasmic
      membrane and that the LppX lipoprotein is essential for the secretion of active
      Xyn1 across the cytoplasmic membranes. In Escherichia coli, wild-type LppX was
      destined for the inner layer of the outer membrane. Mutant LppX(C19A), in which
      Cys-19, a possible lipomodification residue, is replaced with Ala, was located in
      the periplasm without being anchored to the membranes. Another mutant, LppX(S20D
      S21D), with substitutions of Asp for Ser-20 and Ser-21 (conversion to an Asp-Asp
      signal for sorting to the inner membrane), resided on the outer layer of the
      inner membrane, demonstrating that LppX has the sorting property of a
      lipoprotein. E. coli harboring both xyn1 and lppX secreted active Xyn1 into the
      periplasm. In contrast, E. coli carrying xyn1 alone failed to do so, accumulating
      inactive Xyn1 in the cytoplasmic membranes. Exogenous LppX(C19A) liberated the
      inactive Xyn1, which had been stagnating in the inner membrane, into the medium
      as an active enzyme. Thus, we propose that LppX is a novel type of lipoprotein
      that assists Xyn1 in making the proper fold necessary for traveling across the
      cytoplasmic membranes to be secreted as an active enzyme.

PMID- 19103920
TI  - Characterization of the autocleavage process of the Escherichia coli HtrA
      protein: implications for its physiological role.
AB  - The Escherichia coli HtrA protein is a periplasmic protease/chaperone that is
      upregulated under stress conditions. The protease and chaperone activities of
      HtrA eliminate or refold damaged and unfolded proteins in the bacterial periplasm
      that are generated upon stress conditions. In the absence of substrates, HtrA
      oligomerizes into a hexameric cage, but binding of misfolded proteins transforms
      the hexamers into bigger 12-mer and 24-mer cages that encapsulate the substrates
      for degradation or refolding. HtrA also undergoes partial degradation as a
      consequence of self-cleavage of the mature protein, producing short-HtrA protein
      (s-HtrA). The aim of this study was to examine the physiological role of this
      self-cleavage process. We found that the only requirement for self-cleavage of
      HtrA into s-HtrA in vitro was the hydrolysis of protein substrates. In fact,
      peptides resulting from the hydrolysis of the protein substrates were sufficient
      to induce autocleavage. However, the continuous presence of full-length substrate
      delayed the process. In addition, we observed that the hexameric cage structure
      is required for autocleavage and that s-HtrA accumulates only late in the
      degradation reaction. These results suggest that self-cleavage occurs when HtrA
      reassembles back into the resting hexameric structure and peptides resulting from
      substrate hydrolysis are allosterically stimulating the HtrA proteolytic
      activity. Our data support a model in which the physiological role of the self
      cleavage process is to eliminate the excess of HtrA once the stress conditions
      cease.

PMID- 19103921
TI  - A Campylobacter jejuni znuA orthologue is essential for growth in low-zinc
      environments and chick colonization.
AB  - Campylobacter jejuni infection is a leading cause of bacterial gastroenteritis in
      the United States and is acquired primarily through the ingestion of contaminated
      poultry products. Here, we describe the C. jejuni orthologue of ZnuA in other
      gram-negative bacteria. ZnuA (Cj0143c) is the periplasmic component of a putative
      zinc ABC transport system and is encoded on a zinc-dependent operon with Cj0142c
      and Cj0141c, which encode the other two likely components of the transport system
      of C. jejuni. Transcription of these genes is zinc dependent. A mutant lacking
      Cj0143c is growth deficient in zinc-limiting media, as well as in the chick
      gastrointestinal tract. The protein is glycosylated at asparagine 28, but this
      modification is dispensable for zinc-limited growth and chick colonization.
      Affinity-purified FLAG-tagged Cj0143c binds zinc in vitro. Based on our findings
      and on its homology to E. coli ZnuA, we conclude that Cj0143c encodes the C.
      jejuni orthologue of ZnuA.

PMID- 19103922
TI  - Characterization of the Cpx regulon in Escherichia coli strain MC4100.
AB  - The Cpx two-component signal transduction pathway of Escherichia coli mediates
      adaptation to envelope protein misfolding. However, there is experimental
      evidence that at least 50 genes in 34 operons are part of the Cpx regulon and
      many have functions that are undefined or unrelated to envelope protein
      maintenance. No comprehensive analysis of the Cpx regulon has been presented to
      date. In order to identify strongly Cpx-regulated genes that might play an
      important role(s) in envelope protein folding and/or to further define the role
      of the Cpx response and to gain insight into what makes a gene subject to strong
      Cpx regulation, we have carried out a uniform characterization of a Cpx-regulated
      lux reporter library in a single-strain background. Strongly Cpx-regulated genes
      encode proteins that are directly linked to envelope protein folding, localized
      to the envelope but uncharacterized, or involved in limiting the cellular
      concentration of noxious molecules. Moderately Cpx-regulated gene clusters encode
      products implicated in biofilm formation. An analysis of CpxR binding sites in
      strongly regulated genes indicates that while neither a consensus match nor their
      orientation predicts the strength of Cpx regulation, most genes contain a CpxR
      binding site within 100 bp of the transcriptional start site. Strikingly, we
      found that while there appears to be little overlap between the Cpx and Bae
      envelope stress responses, the sigma(E) and Cpx responses reciprocally regulate a
      large group of strongly Cpx-regulated genes, most of which are uncharacterized.

PMID- 19103923
TI  - An intramolecular upstream helix ensures the stability of a toxin-encoding RNA in
      Enterococcus faecalis.
AB  - The par stability determinant is required for the stable inheritance of the
      plasmid pAD1 in its native host, Enterococcus faecalis. It is the only antisense
      RNA-regulated addiction module identified to date in gram-positive bacteria. It
      encodes two small, convergently transcribed RNAs, RNA I and RNA II. RNA I encodes
      the Fst toxin and RNA II acts as the antitoxin by interacting with RNA I
      posttranscriptionally. As the toxin-encoding component of the system, it is
      important that RNA I is more stable than RNA II. This study reveals that a helix
      sequestering the 5' end of RNA I plays a crucial role in maintaining the
      stability of the RNA I. An adjacent structure previously determined to regulate
      Fst translation was not required to enhance stability. Results indicated that
      endoribonuclease J2 contributes significantly to the degradation of a mutant
      disrupting the upstream helix (UH) of RNA I in Bacillus subtilis. Finally, it was
      shown that interaction with RNA II stabilized the UH mutant of RNA I.

PMID- 19103924
TI  - Conditional essentiality of the csrA gene in Escherichia coli.
AB  - CsrA is a global posttranscriptional regulator of numerous physiological
      processes, such as glycogenesis and glycolysis. Here, we show that the csrA gene
      of Escherichia coli is essential for growth on LB and on synthetic medium
      containing glycolytic carbon sources. However, csrA is not necessary for growth
      on synthetic medium containing pyruvate, showing that the Krebs cycle is
      functional in the csrA::cat deletion mutant. Deletion of the glgCAP operon in the
      csrA::cat mutant restored the ability to grow on LB and on synthetic medium
      containing glycolytic carbon sources, showing that growth inhibition is due to an
      excess of glycogen synthesis.

PMID- 19103925
TI  - Retentive memory of bacteria: Long-term regulation of dehalorespiration in
      Sulfurospirillum multivorans.
AB  - The gram-negative, strictly anaerobic epsilonproteobacterium Sulfurospirillum
      multivorans is able to gain energy from dehalorespiration with tetrachloroethene
      (perchloroethylene [PCE]) as a terminal electron acceptor. The organism can also
      utilize fumarate as an electron acceptor. Prolonged subcultivation of S.
      multivorans in the absence of PCE with pyruvate as an electron donor and fumarate
      as an electron acceptor resulted in a decrease of PCE dehalogenase (PceA)
      activity. Concomitantly, the pceA transcript level equally decreased as shown by
      reverse transcriptase PCR. After 35 subcultivations (approximately 105
      generations), a pceA transcript was not detectable and the PceA protein and
      activity were completely absent. In such long-term subcultivated S. multivorans
      cells, the biosynthesis of catalytically active PceA was restored to the initial
      level within about 50 h (approximately three generations) by the addition of PCE
      or trichloroethene. Single colonies obtained from PceA-depleted cultures were
      able to induce PCE dechlorination, indicating that long-term subcultured cells
      still contained the functional pceA gene. The results point to a novel type of
      long-term regulation of PCE dehalogenase gene expression in S. multivorans.

PMID- 19103926
TI  - Hypomodification of the wobble base in tRNAGlu, tRNALys, and tRNAGln suppresses
      the temperature-sensitive phenotype caused by mutant release factor 1.
AB  - In Escherichia coli, release factor 1 (RF1) is one of two RFs that mediate
      termination; it specifically recognizes UAA and UAG stop codons. A mutant allele,
      prfA1, coding for an RF1 that causes temperature-sensitive (Ts) growth at 42
      degrees C, was used to select for temperature-resistant (Ts(+)) suppressors. This
      study describes one such suppressor that is the result of an IS10 insertion into
      the cysB gene, giving a Cys(-) phenotype. CysB is a transcription factor
      regulating the cys regulon, mainly as an activator, which explains the Cys(-)
      phenotype. We have found that suppression is a consequence of the lost ability to
      donate sulfur to enzymes involved in the synthesis of thiolated nucleosides. From
      genetic analyses we conclude that it is the lack of the 5-methylaminomethyl-2
      thiouridine (mnm(5)s(2)U) modification of the wobble base of tRNA(Glu),
      tRNA(Lys), and/or tRNA(Gln) that causes the suppressor phenotype.

PMID- 19103927
TI  - Characterization of a {gamma}-aminobutyric acid transport system of Rhizobium
      leguminosarum bv. viciae 3841.
AB  - Spontaneous mutants of Rhizobium leguminosarum bv. viciae 3841 were isolated that
      grow faster than the wild type on gamma-aminobutyric acid (GABA) as the sole
      carbon and nitrogen source. These strains (RU1736 and RU1816) have frameshift
      mutations (gtsR101 and gtsR102, respectively) in a GntR-type regulator (GtsR)
      that result in a high rate of constitutive GABA transport. Tn5 mutagenesis and
      quantitative reverse transcription-PCR showed that GstR regulates expression of a
      large operon (pRL100242 to pRL100252) on the Sym plasmid that is required for
      GABA uptake. An ABC transport system, GtsABCD (for GABA transport system)
      (pRL100248-51), of the spermidine/putrescine family is part of this operon. GtsA
      is a periplasmic binding protein, GtsB and GtsC are integral membrane proteins,
      and GtsD is an ATP-binding subunit. Expression of gtsABCD from a lacZ promoter
      confirmed that it alone is responsible for high rates of GABA transport, enabling
      rapid growth of strain 3841 on GABA. Gts transports open-chain compounds with
      four or five carbon atoms with carboxyl and amino groups at, or close to,
      opposite termini. However, aromatic compounds with similar spacing between
      carboxyl and amino groups are excellent inhibitors of GABA uptake so they may
      also be transported. In addition to the ABC transporter, the operon contains two
      putative mono-oxygenases, a putative hydrolase, a putative aldehyde
      dehydrogenase, and a succinate semialdehyde dehydrogenase. This suggests the
      operon may be involved in the transport and breakdown of a more complex precursor
      to GABA. Gts is not expressed in pea bacteroids, and gtsB mutants are unaltered
      in their symbiotic phenotype, suggesting that Bra is the only GABA transport
      system available for amino acid cycling.

PMID- 19103928
TI  - sarZ, a sarA family gene, is transcriptionally activated by MgrA and is involved
      in the regulation of genes encoding exoproteins in Staphylococcus aureus.
AB  - The expression of genes involved in the pathogenesis of Staphylococcus aureus is
      controlled by global regulatory loci, including two-component regulatory systems
      and transcriptional regulators (e.g., sar family genes). Most members of the SarA
      family have been partially characterized and shown to regulate a large numbers of
      target genes. Here, we describe the characterization of sarZ, a sarA paralog from
      S. aureus, and its regulatory relationship with other members of its family.
      Expression of sarZ was growth phase dependent with maximal expression in the
      early exponential phase of growth. Transcription of sarZ was reduced in an mgrA
      mutant and returned to a normal level in a complemented mgrA mutant strain, which
      suggests that mgrA acts as an activator of sarZ transcription. Purified MgrA
      protein bound to the sarZ promoter region, as determined by gel shift assays.
      Among the sarA family of genes analyzed, inactivation of sarZ increased sarS
      transcription, while it decreased agr transcription. The expression of potential
      target genes involved in virulence was evaluated in single and double mutants of
      sarZ with mgrA, sarX, and agr. Northern and zymogram analyses indicated that the
      sarZ gene product played a role in regulating several virulence genes,
      particularly those encoding exoproteins. Gel shift assays demonstrated
      nonspecific binding of purified SarZ protein to the promoter regions of the sarZ
      regulated target genes. These results demonstrate the important role played by
      SarZ in controlling regulatory and virulence gene expression in S. aureus.

PMID- 19103930
TI  - Bacteriocin activity of Streptococcus pneumoniae is controlled by the serine
      protease HtrA via posttranscriptional regulation.
AB  - The blp locus of a type 6A strain of Streptococcus pneumoniae encodes a two
      peptide bacteriocin, pneumocin MN, which mediates intraspecies competition during
      mouse nasopharyngeal colonization. This locus is regulated by a quorum-sensing
      mechanism consisting of a dedicated two-component regulatory system and a peptide
      pheromone. Like most clinical isolates, this type 6A strain can be separated into
      opaque and transparent colony variants, each playing a different role during
      pneumococcal infection. In this study, we show that the blp locus is
      differentially regulated at the posttranscriptional level in pneumococcal opacity
      variants. Transparent and opaque variants produce equivalent amounts of blpMNPO
      transcript when stimulated with a synthetic pheromone, but transparent variants
      have no pneumocin MN-mediated inhibitory activity while opaque variants produce
      large zones of inhibitory activity. The differential regulation in opacity
      variants is driven by the two-component regulatory system CiaRH via its
      regulation of the serine protease HtrA. Transparent mutants deficient in CiaH or
      HtrA show increased pneumocin MN-mediated inhibition. In addition, these mutants
      demonstrate alterations in their dose response to a synthetic peptide pheromone,
      suggesting that HtrA activity impacts pneumocin MN production at the level of
      signaling. This, in addition to its known effects on competence, suggests that
      HtrA is a pleiotropic regulator whose protease activity affects several important
      bacterial pathways. The complex regulation of pneumocins may allow the
      pneumococcus to reserve the secretion of active peptides for situations where the
      benefit of their inhibitory activity outweighs the cost of their production.

PMID- 19103929
TI  - Allosteric coupling between the lid and interdomain linker in DnaK revealed by
      inhibitor binding studies.
AB  - The molecular chaperone DnaK assists protein folding and refolding, translocation
      across membranes, and regulation of the heat shock response. In Escherichia coli,
      the protein is a target for insect-derived antimicrobial peptides,
      pyrrhocoricins. We present here the X-ray crystallographic analysis of the E.
      coli DnaK substrate-binding domain in complex with pyrrhocoricin-derived peptide
      inhibitors. The structures show that pyrrhocoricins act as site-specific, dual
      mode (competitive and allosteric) inhibitors, occupying the substrate-binding
      tunnel and disrupting the latch between the lid and the beta-sandwich. Our
      structural analysis revealed an allosteric coupling between the movements of the
      lid and the interdomain linker, identifying a previously unknown mechanism of the
      lid-mediated regulation of the chaperone cycle.

PMID- 19103931
TI  - Identification of a divided genome for VSH-1, the prophage-like gene transfer
      agent of Brachyspira hyodysenteriae.
AB  - The Brachyspira hyodysenteriae B204 genome sequence revealed three VSH-1 tail
      genes, hvp31, hvp60, and hvp37, in a 3.6-kb cluster. The location and
      transcription direction of these genes relative to those of the previously
      described VSH-1 16.3-kb gene operon indicate that the gene transfer agent VSH-1
      has a noncontiguous, divided genome.

PMID- 19103933
TI  - Justice in action? Introduction to the mini symposium on Norman Daniels' Just
      health: meeting health needs fairly.

PMID- 19103932
TI  - Comparative proteomic analysis of the Haemophilus ducreyi porin-deficient mutant
      35000HP::P2AB.
AB  - Haemophilus ducreyi is an obligate human pathogen and the causative agent of the
      sexually transmitted, genital ulcerative disease chancroid. The genome of strain
      35000HP contains two known porin proteins, OmpP2A and OmpP2B. Loss of OmpP2A and
      OmpP2B expression in the mutant 35000HP::P2AB resulted in no obvious growth
      defect or phenotype. Comparison of outer membrane profiles indicated increased
      expression of the 58.5-kDa chaperone, GroEL, in the porin-deficient mutant. A
      proteomics-based comparison resulted in the identification of 231 proteins
      present in membrane-associated protein samples, of which a subset of 56 proteins
      was differentially expressed at a level of 1.5-fold or greater in the porin
      deficient strain 35000HP::P2AB relative to that in 35000HP. Twenty of the
      differentially expressed proteins were selected for real-time PCR, resulting in
      the validation of 90% of the selected subgroup. Proteins identified in these
      studies suggested a decreased membrane stability phenotype, which was verified by
      disk diffusion assay. Loss of OmpP2A and OmpP2B resulted in global protein
      expression changes which appear to compensate for the absence of porin expression
      in 35000HP::P2AB.

PMID- 19103934
TI  - Not so special after all? Daniels and the social determinants of health.
AB  - Just health: meeting health needs fairly is an ambitious book, in which Norman
      Daniels attempts to bring together in a single framework all his work on health
      and justice from the past 25 years. One major aim is to reconcile his earlier
      work on the special moral importance of healthcare with his later work on the
      social determinants of health. In his earlier work, Daniels argued that
      healthcare is of special moral importance because it protects opportunity. In
      this later work, Daniels argues that the social determinants of health (which in
      fact tend to have a larger effect on health outcomes than healthcare does) should
      also be considered special. This paper argues that it is a mistake to base a
      theory of justice for health on the claim that health (or the social determinants
      of health) are "special", for three reasons. First, once we realise that health
      is to a large part socially determined by features such as distribution of
      income, which are also of independent importance for justice, we cannot talk
      about a theory of justice for health in isolation from an overall theory of
      justice. Second, when we are trying to work out the place of health in a general
      theory of justice, being told that health (or the social determinants of health)
      is special is unhelpful. The relevant starting point should rather be whether
      health matters in a fundamental way for justice, or whether it matters merely for
      the effects it has on those goods which are of fundamental importance for
      justice. Third, treating the social determinants of health as special would in
      fact be counterproductive in terms of the broad approach to justice Daniels
      favours.

PMID- 19103935
TI  - Just care: should doctors give priority to patients of low socioeconomic status?
AB  - Growing data on the socioeconomic determinants of health pose a challenge to
      analysis and application of fairness in health. In Just health: meeting health
      needs fairly, Norman Daniels argues for a change in the population end of our
      thinking about just health. What about clinical care? Given our knowledge of the
      importance of wealth, education or social status to health, is fairness in
      medicine served better by continuing to avoid considering our patients' social
      status in setting clinical priorities, or by attempting to equalise existing
      health inequalities by giving priority to the socioeconomically disadvantaged at
      the point of care? In this article, I argue that doctors should not attempt the
      latter. Granted, giving priority to low status would go some way towards
      compensating unjust health inequalities and the impression of being left aside in
      other social spaces. It would represent reverse discrimination, but could still
      be justified inasmuch as disadvantaged groups could be identifiable, and as long
      as the intent was compensation rather than retribution. However, under current
      circumstances such priority would risk being attributed arbitrarily, would
      represent a form of medical proselytising, risk leaving the worst-off with less
      by alienating the powerful, and require teaching doctors to act in strongly
      counter-cultural ways--possibly at great cost. Crucially, however, we protect
      both equal health and equal regard by treating all alike: priority to low status
      would promote the first somewhat, but at the expense of sacrificing the second.

PMID- 19103936
TI  - Justice and procedure: how does "accountability for reasonableness" result in
      fair limit-setting decisions?
AB  - Norman Daniels' theory of justice and health faces a serious practical problem:
      his theory can ground the special moral importance of health and allows
      distinguishing just from unjust health inequalities, but it provides little
      practical guidance for allocating resources when they are especially scarce.
      Daniels' solution to this problem is a fair process that he specifies as
      "accountability for reasonableness". Daniels claims that accountability for
      reasonableness makes limit-setting decisions in healthcare not only legitimate,
      but also fair. This paper assesses the latter claim. Does accountability for
      reasonableness result in fair limit-setting decisions? It is argued that the
      answer to this question is not a clear yes. Daniels is remarkably unclear about
      the criterion of fairness that accountability for reasonableness satisfies. The
      paper discusses different options for resolving this lack of clarity and examines
      how they apply to Daniels' accountability for reasonableness framework. It is
      concluded, first, that accountability for reasonableness is not a paradigm case
      of any of the classic notions of procedural justice; second, that what might be
      called "constrained pure procedural justice" best reflects how accountability for
      reasonableness results in fair limit-setting decisions; and third, that the
      procedural conditions of accountability for reasonableness must be further
      specified and amended to better achieve a fair process, and hence fair limit
      setting decisions.

PMID- 19103937
TI  - On Norman Daniels' interpretation of the moral significance of healthcare.
AB  - According to Norman Daniels, the moral significance of health needs stem from
      their impact on the normal opportunity range: pathological conditions involve
      comparative disadvantage. In this paper I defend an alternative reading of the
      moral importance of healthcare, which focuses on non-comparative aspects of
      disease. In the first section I distinguish two contrasting perspectives on
      pathological conditions, viz a comparative versus a non-comparative. By using
      this distinction I introduce a related disparity regarding the moral importance
      of personal responsibility for disease. I claim that people are usually prepared
      to disregard individual responsibility for disease, if it involves non
      comparative harm, but not if it entails mere disadvantage. Since disadvantage
      means to have less than equal opportunities, Daniels' conception of opportunity
      is vital for his theory. It is therefore scrutinised more closely. I try to show
      that he wavers between two interpretations of the notion of opportunity, which
      are again linked to the distinction between a comparative and a non-comparative
      point of view. Finally, I criticise Daniels' supposition that persons have an
      interest in the normal opportunity range.

PMID- 19103938
TI  - Just health responsibility.
AB  - Although the responsibility for health debate has intensified in several ways
      between Norman Daniels' 1985 Just healthcare and Just health: meeting health
      needs fairly of 2008, comparatively little space is dedicated to the issue in
      Just health, and Daniels notes repeatedly that his account "says nothing about
      personal responsibility for health". Daniels considers health responsibility
      mainly in a particular luck-egalitarian version which he rejects because of its
      potentially unfeasible, penalising and inhumane character. But I show that he
      nonetheless acknowledges and endorses explicitly other dimensions of health
      responsibility. I develop a wider, more nuanced and less punitive concept of
      health responsibility, which expands Daniels' brief consideration and is
      compatible with the overall approach set out in Just health. In its application
      to preventative medicine and health promotion in particular, the concept is
      suited to support and complement the notion that "health is special", which is
      central in Just health. The concept of health responsibility as co-responsibility
      specifies the subjects and objects of health responsibilities. It permits the
      attribution of responsibility without blame and disconnects the question of
      assigning responsibility from decisions about entitlement to treatment or
      different status in prioritisation decisions. This approach secures conceptual
      plausibility and clarity of the concept of health responsibility, is of use in
      policy making, and can help reduce political tensions.

PMID- 19103939
TI  - Age rationing and prudential lifespan account in Norman Daniels' Just health.
AB  - Could age be a valid criterion for rationing? In Just health, Norman Daniels
      argues that under certain circumstances age rationing is prudent, and therefore a
      morally permissible strategy to tackle the problem of resource scarcity. Crucial
      to his argument is the distinction between two problem-settings of
      intergenerational equity: equity among age groups and equity among birth cohorts.
      While fairness between age groups can involve unequal benefit treatment in
      different life stages, fairness between birth cohorts implies enjoying
      approximate equality in benefit ratios. Although both questions of fairness are
      distinct, the resolution of the one depends on resolution of the other. In this
      paper, I investigate whether Daniels' account of age rationing could be defended
      as a fair way of setting limits to healthcare entitlements. I will focus on two
      main points. First, I will consider whether the age group problem could be
      resolved without appealing to a conception of the good. Second, I will
      demonstrate that the connection between the age group problem and the birth
      cohort problem runs deeper than Daniels initially thought-and that it ultimately
      suggests a method for prioritisation in problem solving strategies.

PMID- 19103940
TI  - The multiple self objection to the prudential lifespan account.
AB  - Multiple self approaches purport that to have equal concern about all stages of
      one's life is not a requirement of rationality. This poses a challenge to the
      prudential lifespan account which Norman Daniels advocates in Just health:
      meeting health needs fairly. Daniels has criticised the multiple self approach in
      earlier works, most extensively in Am I my parents keeper? In Just health, he
      only takes up the issue except in one footnote, presumably because he is
      convinced that his preceding discussions settled the matter. This article argues
      that Daniels underestimates the force of the multiple self objection to
      prudential lifespan account.

PMID- 19103941
TI  - Just health: replies and further thoughts.
AB  - This paper responds to discussion and criticism contained in a mini-symposium on
      Just health: meeting health needs fairly. The replies clarify existing positions
      and modify or develop others, specifically in response to the following: Thomas
      Schramme criticises the claim that health is of special importance because of its
      impact on opportunity, and James Wilson argues that healthcare is not of special
      importance if social determinants of health have a major causal impact on
      population health. Annette Rid is concerned that the relevance condition in
      accountability for reasonableness is unclear and does little work. Harald Schmidt
      aims to flesh out where an account of responsibility for health should go since
      one is under-developed in Just health. Michael Schefczyk and Susanne Brauer
      challenge aspects of the prudential lifespan account. Samia Hurst asks what
      impact a population view should have on clinician obligations.

PMID- 19103942
TI  - "Two per cent isn't a lot, but when it comes to death it seems quite a lot
      anyway": patients' perception of risk and willingness to accept risks associated
      with thrombolytic drug treatment for acute stroke.
AB  - BACKGROUND: Thrombolytic drugs to treat an acute ischaemic stroke reduce the risk
      of death or major disability. The treatment is, however, also associated with an
      increased risk of potentially fatal intracranial bleeding. This confronts the
      patient with the dilemma of whether or not to take a risk of a serious side
      effect in order to increase the likelihood of a favourable outcome. OBJECTIVE: To
      explore acute stroke patients' perception of risk and willingness to accept risks
      associated with thrombolytic drug treatment. DESIGN: Eleven patients who had been
      informed about thrombolytic drug treatment and had been through the process of
      deciding whether or not to participate in a thrombolytic drug trial went through
      repeated qualitative, semistructured interviews. RESULTS: Many patients showed a
      limited perception of the risks connected with thrombolytic drug treatment. Some
      perceived the risk as not relevant to them and were reluctant to accept that
      treatment could cause harm. Others seemed to be aware that treatment would mean
      exposure to risk. The patients' willingness to take a risk also varied
      substantially. Several statements revealed ambiguity and confusion about being
      involved in a decision about treatment. The patients' reasoning about risk was
      put into the context of their health-related experiences and life histories.
      Several patients wanted the doctor to be responsible for the decisions.
      CONCLUSION: Acute stroke patients' difficulties in perceiving and processing
      information about risk may reduce their ability to be involved in clinical
      decisions where risks are involved.

PMID- 19103943
TI  - Optimising the documentation practices of an Ethics Consultation Service.
AB  - A formal Ethics Consultation Service (ECS) can provide significant help to
      patients, families and hospital staff. As with any other form of clinical
      consultation, documentation of the process and the advice rendered is very
      important. Upon review of the published consult documentation practices of other
      ECSs, we judged that none of them were sufficiently detailed or structured to
      meet the needs and purposes of a clinical ethics consultation. Thus, we decided
      to share our method in order to advance the practice of ethics consultation.
      Here, we describe a method of ECS documentation practice, including use of a
      formal consult report template, as well as a log for maintaining a chronological
      record of the consultations performed. These two documents facilitate order and
      organisation of the ECS. They also enable the ECS to keep an account of
      professional time and experience, enable quick consult trend assessments (by
      consult theme or ward, for example) and establish a potential registry of
      consults for future research study. This method of documentation, we believe, not
      only contributes significantly to the primary purpose of the consultation-namely,
      the evincing and sharing of ethical opinion about a case-but also enables
      consultants to improve their practice and to pursue research on clinical ethics
      consultation.

PMID- 19103944
TI  - An interaction of medical and statistical ethics.
AB  - It is argued that the practice of omitting outliers when calibrating
      thromboplastin time, as recommended by the World Health Organization, should not
      continue unless it can be justified statistically and that possible harmful
      effects of omitting such data should be investigated.

PMID- 19103945
TI  - The fair innings argument and increasing life spans.
AB  - The fair innings argument maintains that for healthcare resources to be
      distributed fairly every person should receive sufficient healthcare to provide
      them with the opportunity to live in good health for a normal span of years. What
      constitutes a normal span of years is often defined as life expectancy at birth,
      but this criterion fails to provide adequate grounds for the equal distribution
      of healthcare across and between generations. A more suitable criterion for the
      normal life span is the idea that the human life span is biologically limited.
      Many current gerontological theories argue that the biological limit to human
      life spans is related to the ageing process. If technological advances in
      medicine can retard the ageing process by treating and preventing the diseases
      and disorders associated with it, human longevity will be limited only by the
      developments in and the successful application of medicine. In consequence, the
      fair innings argument will no longer be able to justify denying people healthcare
      resources because they have lived longer than the normal life span.

PMID- 19103946
TI  - Can a moral reasoning exercise improve response quality to surveys of healthcare
      priorities?
AB  - OBJECTIVE: To determine whether a moral reasoning exercise can improve response
      quality to surveys of healthcare priorities METHODS: A randomised internet survey
      focussing on patient age in healthcare allocation was repeated twice. From 2574
      internet panel members from the USA and Canada, 2020 (79%) completed the baseline
      survey and 1247 (62%) completed the follow-up. We elicited respondent preferences
      for age via five allocation scenarios. In each scenario, a hypothetical health
      planner made a decision to fund one of two programmes identical except for
      average patient age (35 vs 65 years). Half of the respondents (intervention
      group) were randomly assigned to receive an additional moral reasoning exercise.
      Responses were elicited again 7 weeks later. Numerical scores ranging from -5
      (strongest preference for younger patients) to +5 (strongest preference for older
      patients); 0 indicates no age preference. Response quality was assessed by
      propensity to choose extreme or neutral values, internal consistency, temporal
      stability and appeal to prejudicial factors. RESULTS: With the exception of a
      scenario offering palliative care, respondents preferred offering scarce
      resources to younger patients in all clinical contexts. This preference for
      younger patients was weaker in the intervention group. Indicators of response
      quality favoured the intervention group. CONCLUSIONS: Although people generally
      prefer allocating scarce resources to young patients over older ones, these
      preferences are significantly reduced when participants are encouraged to reflect
      carefully on a wide range of moral principles. A moral reasoning exercise is a
      promising strategy to improve response quality to surveys of healthcare
      priorities.

PMID- 19103947
TI  - Understanding ethics guidelines using an internet-based expert system.
AB  - National and international guidelines outlining ethical conduct in research
      involving humans and animals have evolved into large and complex documents making
      the process of gaining ethics approval a complicated task for researchers in the
      area. Researchers, in particular those who are relatively new to the ethics
      approval process, can struggle to understand the parts of an ethics guideline
      that apply to their research and the nature of their ethical obligations to trial
      participants. With the scope of medical research likely to continue to expand in
      the future, it is clear that ethics guidelines will only increase in complexity
      and number. This paper describes one possible solution to the PROBLEM: the use of
      an internet-based expert system to intelligently and interactively distribute the
      information stored in ethics guidelines to individual researchers. This paper
      also details how one such system was designed and tested with respect to
      Australian medical research ethics guidelines.

PMID- 19103948
TI  - Can we justify eliminating coercive measures in psychiatry?
AB  - The practice of coercive measures in psychiatry is controversial. Although some
      have suggested that it may be acceptable if patients are a danger to others or to
      themselves, others committed themselves to eliminate it. Ethical, legal and
      clinical considerations become more complex when the mental incapacity is
      temporary and when the coercive measures serve to restore autonomy. We discuss
      these issues, addressing the conflict between autonomy and beneficence/non
      maleficence, human dignity, the experiences of patients and the effects of
      coercive measures. We argue that an appeal to respect autonomy and/or human
      dignity cannot be a sufficient reason to reject coercive measures. All together,
      these ethical aspects can be used both to support and to reject a non-seclusion
      approach. The total lack of controlled trials about the beneficial effects of
      coercive measures in different populations however, argues against the use of
      coercive measures.

PMID- 19103950
TI  - A comparison of journal instructions regarding institutional review board
      approval and conflict-of-interest disclosure between 1995 and 2005.
AB  - OBJECTIVES: To compare 2005 and 1995 ethics guidelines from journal editors to
      authors regarding requirements for institutional review board (IRB) approval and
      conflict-of-interest (COI) disclosure. DESIGN: A descriptive study of the ethics
      guidelines published in 103 English-language biomedical journals listed in the
      Abridged Index Medicus in 1995 and 2005. Each journal was reviewed by the
      principal author and one of four independent reviewers. RESULTS: During the
      period, the proportion of journals requiring IRB approval increased from 42% (95%
      CI 32.2% to 51.2%, p<0.001) to 76% (95% CI 66.4% to 83.1%, p<0.001). In 2005, an
      additional 9% referred to the Declaration of Helsinki or the International
      Committee of Medical Journal Editors' Uniform requirements for ethical
      guidelines; 15% (95% CI 8.5% to 22.5%, p<0.01) provided ambiguous or no
      requirements. The proportion of journals requiring COI disclosure increased from
      75% (95% CI 66.6% to 83.3%, p<0.05) to 94% (95% CI 89.4% to 98.6%, p<0.05); 41%
      had comprehensive requirements, while some addressed only funding source (6%),
      were vague (10%) or both (14%). Criteria for authorship rose from 40% (95% CI
      30.5% to 49.5%, p<0.05) to 72% (95% CI 63.3% to 80.7%, p<0.05). Journals with
      higher impact factors were more likely to require IRB approval (p<0.01). Journals
      in anaesthesia and radiology all required IRB approval; requirements in other
      disciplines varied. CONCLUSIONS: Instructions to authors regarding ethical
      standards have improved. Some remain incomplete, especially regarding the scope
      of disclosure of COI. The ethical guidelines presented to authors need further
      clarification and standardisation.

PMID- 19103951
TI  - The poly(A)-dependent degradation pathway of rpsO mRNA is primarily mediated by
      RNase R.
AB  - Polyadenylation is an important factor controlling RNA degradation and RNA
      quality control mechanisms. In this report we demonstrate for the first time that
      RNase R has in vivo affinity for polyadenylated RNA and can be a key enzyme
      involved in poly(A) metabolism. RNase II and PNPase, two major RNA exonucleases
      present in Escherichia coli, could not account for all the poly(A)-dependent
      degradation of the rpsO mRNA. RNase II can remove the poly(A) tails but fails to
      degrade the mRNA as it cannot overcome the RNA termination hairpin, while PNPase
      plays only a modest role in this degradation. We now demonstrate that in the
      absence of RNase E, RNase R is the relevant factor in the poly(A)-dependent
      degradation of the rpsO mRNA. Moreover, we have found that the RNase R
      inactivation counteracts the extended degradation of this transcript observed in
      RNase II-deficient cells. Elongated rpsO transcripts harboring increasing poly(A)
      tails are specifically recognized by RNase R and strongly accumulate in the
      absence of this exonuclease. The 3' oligo(A) extension may stimulate the binding
      of RNase R, allowing the complete degradation of the mRNA, as RNase R is not
      susceptible to RNA secondary structures. Moreover, this regulation is shown to
      occur despite the presence of PNPase. Similar results were observed with the rpsT
      mRNA. This report shows that polyadenylation favors in vivo the RNase R-mediated
      pathways of RNA degradation.

PMID- 19103952
TI  - Development of CD4+CD25+FoxP3+ regulatory T cells from cord blood hematopoietic
      progenitor cells.
AB  - Adult stem cells are capable of generating all of the cells of the hematopoietic
      system, and this process is orchestrated in part by the interactions between
      these cells and the stroma. T cell progenitors emerge from the stem cell
      compartment and migrate to the thymus, where their terminal differentiation and
      maturation occur, and it is during this phase that selection shapes the immune
      repertoire. Notch ligands, including Delta-like 1 (DL1), play a critical role in
      this lymphoid differentiation. To mimic this in vitro, stroma-expressing DL1 have
      been used to generate CD4(+)CD8(+) double-positive and single-positive T cells
      from hematopoietic stem/progenitor cells. This system provides a robust tool to
      investigate thymopoiesis; however, its capacity to generate regulatory T cells
      (Tregs) has yet to be reported. Natural Tregs (nTregs) develop in the thymus and
      help maintain immune homeostasis and have potential clinical use as a cell
      therapy for modulation of autoimmune disease or for transplant tolerization.
      Here, we describe for the first time the development of a population of
      CD4(+)CD25(+) CD127(lo)FoxP3(+) cells that emerge in coculture of cord blood (CB)
      CD34(+) progenitors on OP9-DL1 stroma. These hematopoietic progenitor-derived
      CD4(+)CD25(+) Tregs have comparable suppressor function with CB nTregs in vitro.
      The addition of IL-2 to the coculture enhanced the expansion and survival of this
      population significantly. This manipulable culture system, therefore, generates
      functional Tregs and provides a system to elucidate the mechanism of Treg
      development.

PMID- 19103953
TI  - Reference ranges still need further clarity.

PMID- 19103954
TI  - Standardization of vitamin D assays: art or science?

PMID- 19103955
TI  - Reference intervals: the way forward.
AB  - New facts have recently enhanced interest in the topic of reference intervals. In
      particular, the International Organization for Standardization standard 15189,
      requesting that 'biological reference intervals shall be periodically reviewed',
      and the directive of the European Union on in vitro diagnostic medical devices
      asking manufacturers to provide detailed information on reference intervals, have
      renewed interest in the subject. This review presents an update on the topic,
      discussing the theoretical aspects and the most critical issues. The basic
      approach to the definition of reference intervals proposed in the original
      International Federation of Clinical Chemistry documents still remain valid. The
      use of data mining to obtain reference data from existing databases has severe
      limitations. New statistical approaches to discard outliers and to compute
      reference limits have been recommended. On the other hand, perspectives opened by
      the improvement in standardization through the implementation of the concept of
      traceability suggest new models to define 'common' reference intervals that can
      be transferred and adopted by different clinical laboratories in order to
      decrease the proliferation of different reference intervals not always justified
      by differences in population characteristics or in analytical methodology.

PMID- 19103956
TI  - Appropriate laboratory utilization in diagnosing pulmonary embolism.
AB  - BACKGROUND: The appropriateness of clinical laboratory use in hospital clinical
      practice is a very debated question. In fact diagnostic tests are essential tools
      for disease screening or diagnosis but at the same time they represent an
      important expenditure. METHODS: A quantitative study was conducted in an Italian
      general hospital with 535 beds and about 27,000 admissions per year. The sample
      was made of all patients discharged from the hospital with DRG 78 between the
      period 1 January 2005 and 31 December 2005. RESULTS: The Emergency Department
      (ED) discharged 2.9% (116/4009) of patients with pulmonary embolism diagnosis in
      the year 2005. The percentage of prescription inappropriateness inferred by
      analysis of all required tests by operative unit was 21.7% (950/4385). The
      approximate estimate of the economic value of unnecessarily required tests was of
      3495 euro. Of these 96.5% (112/116) had enlisting criteria. All haematological
      and clinical-chemical tests (1295) concerning studied patients were analysed.
      About 70.4% (93/132) of d-dimer tests were ordered in ED. In the studied
      patients, unfractionated heparin was administered in 17.8% (20/112) of the cases,
      low-molecular weight heparin in 79.5% (89/112) and heparin therapy was not
      administered in 2.7% (three of 112). CONCLUSION: This study uses a method to
      assess the quality of laboratory test orders using results as a tool to estimate
      the impact of economic resources devolved in executing inappropriate tests.

PMID- 19103957
TI  - Lithocholic acid as a biomarker of intrahepatic cholestasis of pregnancy during
      ursodeoxycholic acid treatment.
AB  - BACKGROUND: The diagnosis and treatment of intrahepatic cholestasis of pregnancy
      (ICP) has important implications on fetal health. The biochemical parameter
      commonly used in the diagnosis of ICP is the determination of the concentration
      of total serum bile acids (TSBA). However, bile acid profile, especially
      lithocholic acid (LCA) analysis is a more sensitive and specific biomarker for
      differential diagnosis of this pathology and also could be an alternative to
      evaluate the efficiency of ursodeoxycholic acid (UDCA) for ICP treatment.
      METHODS: Serum bile acid (SBA) profiles including LCA determination, were studied
      in 28 ICP patients using a capillary electrophoresis method. The effects of UDCA
      treatment on bile acid profile, were analysed in 23 out of 28 ICP patients and
      the two samples obtained before and 15 days after treatment were compared. Two
      samples taken as controls were also obtained from each of five patients without
      therapy. RESULTS: A dramatic decrease in LCA concentrations and maintenance of
      TSBA concentrations were found in all patients after UDCA therapy, whereas SBA
      profiles together with LCA values did not change in patients without therapy.
      CONCLUSION: We propose LCA as an alternative biomarker and a more sensitive
      parameter than TSBA to evaluate the effectiveness of UDCA treatment, at least in
      ICP patients from Argentina.

PMID- 19103958
TI  - Criteria for opiate identification using liquid chromatography linked to tandem
      mass spectrometry: problems in routine practice.
AB  - BACKGROUND: Liquid chromatography linked to tandem mass spectrometry (LC/MS/MS)
      is being increasingly used for drug confirmation. At present, no official
      criteria exist for drug identification using this technique although the European
      Union (EU) criteria for compound identification have been adopted. These criteria
      are evaluated with respect to opiate confirmation by LC/MS/MS and problems
      highlighted. METHODS: Urine samples screened positive for opiates by immunoassay
      were subjected to confirmation by LC/MS/MS using multiple reaction monitoring
      (MRM) and two separate buffer systems of pH 6.8 and 8.0, respectively. The EU
      criteria for compound identification were applied for confirmation of morphine, 6
      monoacetylmorphine (6MAM), codeine and dihydrocodeine (DHC). RESULTS: Using the
      pH 6.8 buffer, confirmation could be achieved for 84%, 94%, 96% and 95%,
      respectively, for samples demonstrating MRM chromatographic peaks at retention
      times for morphine, 6MAM, codeine and DHC. Failure to meet the EU criteria was
      mainly attributed to low signal-to-noise (S:N) ratios or excessively high drug
      concentrations. Isobaric interferences and poor chromatography were also
      contributing factors. The identification of morphine was considerably improved
      with chromatography at pH 8.0 owing to resolution of interferences. Oxycodone
      metabolites were a potential problem for the identification of DHC. CONCLUSION:
      Isobaric interferences can pose a problem with drug identification using
      LC/MS/MS. Optimizing chromatographic conditions is important to overcome these
      interferences. Consideration needs to be given to investigating drug metabolites
      as well as parent drugs in method development.

PMID- 19103960
TI  - A meta-analysis of leptin reference ranges in the healthy paediatric prepubertal
      population.
AB  - OBJECTIVE: The initial discovery of leptin (1994) has given rise to a substantial
      number of published studies. This study aimed at identifying the published data
      on the reference ranges of total, free and bound leptin concentration in the
      healthy prepubertal population. METHODS: A search was conducted on original
      English language studies published from 1994 to 2005 in the following databases:
      PubMed (n = 58), EMBASE (n = 4), Biological Abstracts (n = 2) and Science Finder
      Scholar (n = 66). A cited reference search was completed in Science Citation
      Index on studies with a leptin range. A meta-analysis was completed on included
      studies containing a dataset and a sample size for a leptin concentration range
      and/or mean+/-standard deviation for a healthy prepubertal population.
      Preanalytical and analytical variations were examined. Preanalytical variables
      included aspects such as fasting state and gender, while analytical variation
      comprised the type of leptin assay methodology. RESULTS: Twelve studies met the
      inclusion criteria. One study examined free leptin; 11 studies examined total
      concentration. No studies reported leptin reference ranges established by
      Clinical and Laboratory Standards Institute (CLSI) criteria, although four
      studies reported specific study leptin ranges. The methodology of enzyme-linked
      immunosorbent assay demonstrated a wider leptin range than radio immunoassay
      (0.56-36.35 vs. 1.01-12.21 ng/mL). Males had a significantly lower mean leptin
      concentration than females (P = 0.0006); obese children had a higher
      concentration than non-obese (P = 0.0001). CONCLUSION: No studies have
      established CLSI-based leptin reference ranges in prepubertal healthy children
      and there is a wide variation in the published leptin concentrations. These
      differences suggest that caution should be used in the interpretation and
      comparison between studies.

PMID- 19103959
TI  - Evaluation of the Modification of Diet in Renal Disease equation (eGFR) against
      simultaneous, dual-marker multi-sample measurements of glomerular filtration
      rate.
AB  - BACKGROUND: Estimation of glomerular filtration rate (GFR) using plasma
      creatinine remains controversial, especially when GFR approaches normal values.
      The aim was to re-examine estimated GFR (eGFR) using dual-reference GFR
      measurements. METHODS: eGFR (simplified modified Modification of Diet in Renal
      Disease equation) was compared with GFR measured with iohexol for predicting GFR
      measured with (51)Cr-ethylenediaminetetraacetic acid (EDTA). Dual six-sample GFR
      (20-240 min postinjection) was measured in 60 patients and 20 normal volunteers
      with (51)Cr-EDTA (GFR(EDTA)) and iohexol (GFR(iohexol)) injected into separate
      arms and sampled contralaterally. This was repeated in the normal volunteers
      under fasting conditions (twice in nine). Percentage bias, imprecision (SD of
      bias) and disagreement (sign-less difference) between eGFR and GFR(EDTA) were
      compared with those between GFR(iohexol) and GFR(EDTA). RESULTS: Changes between
      fasting and postprandial eGFR correlated significantly with corresponding changes
      in GFR(iohexol) and GFR(EDTA). eGFR predicted GFR(EDTA) less precisely (SD 19.9%)
      than GFR(iohexol) (10.5%; P < 0.01). Although eGFR showed a poorer correlation
      with GFR(EDTA) when GFR(EDTA) > 80 mL/min/1.73 m(2) compared with <80 mL/min/1.73
      m(2), there was no significant difference with respect to imprecision or
      disagreement of >20 or 30%. However, eGFR was closer than GFR(iohexol) to
      GFR(EDTA) in a higher fraction of studies when GFR(EDTA) > 80 mL/min/1.73 m(2)
      (28/60) than when it was <80 mL/min/1.73 m(2) (9/37; P < 0.05). CONCLUSION: eGFR
      is inferior to GFR(iohexol) for predicting GFR(EDTA). The disagreement between
      GFR(iohexol) and GFR(EDTA) illustrates the extent to which uncertainty in
      GFR(EDTA) contributes to the performance of eGFR. eGFR performs no better at
      lower, compared with higher levels of GFR.

PMID- 19103961
TI  - A reference interval for sweat chloride in infants aged between five and six
      weeks of age.
AB  - BACKGROUND: This study was designed to establish a reference interval for sweat
      chloride for infants without evidence of cystic fibrosis (CF), aged between 5 wk
      and 6 wk, a time when sweat testing is an integral part of newborn screening for
      CF. In addition, we compared the gold standard method of sweat testing
      (quantitative pilocarpine iontophoresis [QPIT, coulometry]) with an emerging
      methodology (Macroduct [ISE]). METHODS: This was a prospective study on healthy
      infants at 5-6 wk of age. Sweat collection was undertaken at home on both outer
      thigh areas using two methods (QPIT and Macroduct ). The order of testing was
      randomly assigned. Filter paper samples (QPIT) were analysed using flame
      photometry and coulometry. Macroduct samples were analysed using ion-selective
      electrodes (ISE, Abbott Architect c8000, UK). RESULTS: Insufficient sweat was
      collected on 28 occasions with the QPIT (coulometry) method and on 31 with the
      Macroduct (ISE) capillary system. We achieved a 92% success rate in undertaking
      two sweat collections consecutively (n = 177). Sweat chloride concentrations were
      normally distributed with excellent limits of agreement between the two methods
      of sweat collection and analysis (n = 150). Median (IQR) sweat chloride was 11.2
      mmol/L (8-13) with QPIT (coulometry) method with a 99.5th centile (n = 165) of 24
      mmol/L. CONCLUSION: The Macroduct (ISE) capillary sweat collection system is
      valid in this age group. Sweat chloride concentrations above 30 mmol/L should
      prompt assessment in a specialist CF centre.

PMID- 19103962
TI  - Use of a common standard improves the performance of liquid chromatography-tandem
      mass spectrometry methods for serum 25-hydroxyvitamin-D.
AB  - BACKGROUND: Liquid chromatography-tandem mass spectrometry (LC-MS/MS) is becoming
      increasingly popular for measuring 25-hydroxyvitamin-D (25-OH-D). Results
      submitted to the International Quality Assessment Scheme (DEQAS) have shown poor
      interlaboratory agreement. We investigated whether the use of a common standard
      would reduce interlaboratory imprecision. METHODS: A commercial standard and two
      controls were distributed with the DEQAS samples in January 2008. Participants
      were asked to calculate the results of samples and controls using their usual
      standard and the commercial standard. A method questionnaire was also
      distributed. RESULTS: Use of a common standard reduced the mean interlaboratory
      imprecision (coefficient of variation [CV]) for total 25-OH-D from 16.4% (in
      house standards) to 10.4% (common standard). For 25-OH-D(3) and 25-OH-D(2), the
      mean CVs were reduced from 16.7% and 21.1% to 8.5% and 12.6%, respectively. Mean
      values obtained for total 25-OH-D using the common standard were higher by 6.1%.
      CONCLUSIONS: Use of a common standard improved agreement among laboratories using
      LC-MS/MS methods for 25-OH-D. This suggests that problems with assay
      standardization contribute to interlaboratory imprecision. This may be related to
      the nature of the matrix used for working standards or errors in the calibration
      of stock standard solutions of 25-OH-D. Some participants used a gravimetric
      method, others UV spectrophotometry, to establish the concentration of stock
      solutions. Among the latter group there was uncertainty over the molar absorption
      coefficient of 25-OH-D solutions. We conclude that LC-MS/MS is not yet
      sufficiently robust to become the reference method for 25-OH-D and that gas
      chromatography-mass spectrometry might be a more suitable candidate.

PMID- 19103963
TI  - Trp64Arg polymorphisms of the beta3-adrenergic receptor gene and systemic
      disorders of metabolism: a close association.

PMID- 19103965
TI  - Consensus meeting on reporting glycated haemoglobin and estimated average glucose
      in the UK: time for 'Kilpatrick's Kludge'?

PMID- 19103966
TI  - Do interpretative comments influence patient management and do our users approve
      of the laboratory 'adding on' requests? A follow-up General Practitioner and
      Nurse Practitioner survey.

PMID- 19103967
TI  - Response to Iqbal et al. Ann Clin Biochem 2008;45:504-7.

PMID- 19103968
TI  - Is high-throughput measurement of 25-hydroxyvitamin D3 without 25-hydroxyvitamin
      D2 appropriate for routine clinical use?

PMID- 19103970
TI  - Structural integration in language and music: evidence for a shared system.
AB  - In this study, we investigate whether language and music share cognitive
      resources for structural processing. We report an experiment that used sung
      materials and manipulated linguistic complexity (subject-extracted relative
      clauses, object-extracted relative clauses) and musical complexity (in-key
      critical note, out-of-key critical note, auditory anomaly on the critical note
      involving a loudness increase). The auditory-anomaly manipulation was included in
      order to test whether the difference between in-key and out-of-key conditions
      might be due to any salient, unexpected acoustic event. The critical dependent
      measure involved comprehension accuracies to questions about the propositional
      content of the sentences asked at the end of each trial. The results revealed an
      interaction between linguistic and musical complexity such that the difference
      between the subject- and object-extracted relative clause conditions was larger
      in the out-of-key condition than in the in-key and auditory-anomaly conditions.
      These results provide evidence for an overlap in structural processing between
      language and music.

PMID- 19103971
TI  - Domain-specific learning of grammatical structure in musical and phonological
      sequences.
AB  - Artificial grammar learning depends on acquisition of abstract structural
      representations rather than domain-specific representational constraints, or so
      many studies tell us. Using an artificial grammar task, we compared learning
      performance in two stimulus domains in which respondents have differing tacit
      prior knowledge. We found that despite grammatically identical sequence
      structures, learning was better for harmonically related chord sequences than for
      letter name sequences or harmonically unrelated chord sequences. We also found
      transfer effects within the musical and letter name tasks, but not across the
      domains. We conclude that knowledge acquired in implicit learning depends not
      only on abstract features of structured stimuli, but that the learning of
      regularities is in some respects domain-specific and strongly linked to
      particular features of the stimulus domain.

PMID- 19103972
TI  - The influence of category coherence on inference about cross-classified entities.
AB  - A critical function of categories is their use in property inference (Heit,
      2000). However, one challenge to using categories in inference is that most
      entities in the world belong to multiple categories (e.g., Fido could be a dog, a
      pet, a mammal, or a security system). Building on Patalano, Chin-Parker, and Ross
      (2006), we tested the hypothesis that category coherence (the extent to which
      category features go together in light of prior knowledge) influences the
      selection of categories for use in property inference about cross-classified
      entities. In two experiments, we directly contrasted coherent and incoherent
      categories, both of which included cross-classified entities as members, and we
      found that the coherent categories were used more readily as the source of both
      property transfer and property extension. We conclude that category coherence,
      which has been found to be a potent influence on strength of inference for singly
      classified entities (Rehder & Hastie, 2004), is also central to category use in
      reasoning about novel cross-classified ones.

PMID- 19103973
TI  - The influence of causal information on judgments of treatment efficacy.
AB  - How does the causal structure of a problem concept influence judgments of
      treatment efficacy? We argue that the task of evaluating treatment efficacy
      involves a combination of causal reasoning and categorization. After an exemplar
      has been categorized, a treatment task involves judging where to intervene in the
      causal structure to eradicate the problem, removing the exemplar from category
      membership. We hypothesized that the processes underlying such category
      membership removal tasks are not identical to those underlying categorization.
      Whereas previous experiments have shown that both the root cause (as the most
      generative feature) and the coherence of the exemplar heavily influence
      categorization, Experiments 1 and 2 showed that people base category membership
      removal judgments on the root cause. In Experiment 3, people spontaneously chose
      to remove an exemplar from category membership when asked to treat the terminal
      effect. We discuss how our findings are compatible with existing models of
      categorization. A description of pilot studies for Experiment 1 may be downloaded
      as supplemental materials from mc.psychonomic-journals.org.

PMID- 19103974
TI  - Schematic knowledge changes what judgments of learning predict in a source memory
      task.
AB  - Source monitoring can be influenced by information that is external to the study
      context, such as beliefs and general knowledge (Johnson, Hashtroudi, & Lindsay,
      1993). We investigated the extent to which metamnemonic judgments predict memory
      for items and sources when schematic information about the sources is or is not
      provided at encoding. Participants made judgments of learning (JOLs) to
      statements presented by two speakers and were informed of the occupation of each
      speaker either before or after the encoding session. Replicating earlier work,
      prior knowledge decreased participants' tendency to erroneously attribute
      statements to schematically consistent but episodically incorrect speakers. The
      origin of this effect can be understood by examining the relationship between
      JOLs and performance: JOLs were equally predictive of item and source memory in
      the absence of prior knowledge, but were exclusively predictive of source memory
      when participants knew of the relationship between speakers and statements during
      study. Background knowledge determines the information that people solicit in
      service of metamnemonic judgments, suggesting that these judgments reflect
      control processes during encoding that reduce schematic errors.

PMID- 19103975
TI  - Remembering words not presented in sentences: how study context changes patterns
      of false memories.
AB  - People falsely endorse semantic associates and morpheme rearrangements of studied
      words at high rates in recognition testing. The coexistence of these results is
      paradoxical: Models of reading that presume automatic extraction of meaning
      cannot account for elevated false memory for foils that are related to studied
      stimuli only by their visual form; models without such a process cannot account
      for false memory for semantic foils. Here we show how sentence and list study
      contexts encourage different encoding modes and consequently lead to different
      patterns of memory errors. Participants studied compound words, such as tailspin
      and floodgate, as single words or embedded in sentences. We show that sentence
      contexts led subjects to be better able to discriminate conjunction lures (e.g.,
      tailgate) from old words than did list contexts. Conversely, list contexts led to
      superior discrimination of semantic lures (e.g., nosedive) from old words than
      did sentence contexts.

PMID- 19103977
TI  - Beyond sentence boundaries: grammatical gender information in short-term recall
      of texts.
AB  - In the context of text recall it is often stated that surface representations are
      quickly forgotten. Jarvella (1971) and Sachs (1967) argued that what is retained
      beyond sentence boundaries is meaning information, whereas lexical and syntactic
      information is only available for the most recent constituent. We based a text
      recall experiment on Jarvella's paradigm, in order to demonstrate that both
      meaning and grammatical gender information contribute to the recall of short text
      passages. Although it is known that grammatical gender information is used in
      anaphor resolution, even if noun and pronoun do not belong to adjacent sentences,
      there is no direct evidence for a gender contribution to text memory so far. The
      present experiment demonstrates that grammatical gender information, even when of
      no semantic importance, is retained beyond sentence boundaries and can contribute
      to the memory representation of subsequent text. All materials and additional
      statistics may be downloaded from mc.psychonomic
      journals.org/content/supplemental.

PMID- 19103976
TI  - Target strength and retrieval-induced forgetting in semantic recall.
AB  - Retrieval-induced forgetting (RIF) occurs when practice of a memory item impairs
      retrieval of related, unpracticed items. Here, we demonstrated that RIF in
      semantic memory is retrieval dependent. University students either studied (7 x 8
      = 56) or retrieved (7 x 8 = ?) the answers to a set of multiplication problems
      for 40 blocks and then were tested on their addition counterparts (7 + 8 = ?).
      For the retrieval practice group, but not the study practice group, response time
      for the multiplication-practiced addition facts was about 100 msec slower,
      relative to control addition problems, in the first of five postpractice addition
      blocks. Subsequent blocks of addition were interleaved with retrieval blocks of
      all the multiplication counterparts, which permitted measurement of RIF for the
      control addition problems after only a single retrieval of their multiplication
      counterparts. The control problems presented RIF in excess of 200 msec, much
      larger than the RIF observed after massive practice. This is consistent with the
      hypothesis that inhibition of competitors should be weaker when target strength
      is high than when target strength is only moderate (Anderson, 2003; Norman,
      Newman, & Detre, 2007). The evidence that RIF in semantic retrieval is both
      retrieval dependent and weaker following massive target practice than following
      moderate target practice provides strong support for inhibition-based theories of
      RIF.

PMID- 19103978
TI  - Does feigning amnesia impair subsequent recall?
AB  - Defendants who are accused of serious crimes sometimes feign amnesia to evade
      criminal responsibility. Previous research has suggested that feigning amnesia
      might impair subsequent recall. In two experiments, participants read and heard a
      story about a central character, described as "you," who was responsible for the
      death of either a puppy (Experiment 1) or a friend (Experiment 2). On free and
      cued recall tests immediately after the story, participants who had feigned
      amnesia recalled less than did participants who had recalled accurately. One week
      later, when all participants recalled accurately, participants who had previously
      feigned amnesia still performed worse than did participants who had recalled
      accurately both times. However, the participants who had formerly feigned amnesia
      did not perform worse than did a control group who had received only the delayed
      recall tests. Our results suggest that a "feigned amnesia effect" may reflect
      nothing more than differential practice at recall. Feigning amnesia for a crime
      need not impair memory for that crime when a person later seeks to remember
      accurately.

PMID- 19103979
TI  - Learning scenes from multiple views: novel views can be recognized more
      efficiently than learned views.
AB  - In two experiments, participants were trained to recognize a playground scene
      from four vantage points and were subsequently asked to recognize the playground
      from a novel perspective between the four learned viewing perspectives, as well
      as from the trained perspectives. In both experiments, people recognized the
      novel view more efficiently than those that they had recently used in order to
      learn the scene. Additionally, in Experiment 2, participants who viewed a novel
      stimulus on their very first test trial correctly recognized it more quickly (and
      also tended to recognize it more accurately) than did participants whose first
      test trial was a familiar view of the scene. These findings call into question
      the idea that scenes are recognized by comparing them with single previous
      experiences, and support a growing body of literature on the existence of
      psychological mechanisms that combine spatial information from multiple views of
      a scene.

PMID- 19103980
TI  - Associative and repetition priming with the repeated masked prime technique: no
      priming found.
AB  - Wentura and Frings (2005) reported evidence of subliminal categorical priming on
      a lexical decision task, using a new method of visual masking in which the prime
      string consisted of the prime word flanked by random consonants and random letter
      masks alternated with the prime string on successive refresh cycles. We
      investigated associative and repetition priming on lexical decision, using the
      same method of visual masking. Three experiments failed to show any evidence of
      associative priming, (1) when the prime string was fixed at 10 characters (three
      to six flanking letters) and (2) when the number of flanking letters were reduced
      or absent. In all cases, prime detection was at chance level. Strong associative
      priming was observed with visible unmasked primes, but the addition of flanking
      letters restricted priming even though prime detection was still high. With
      repetition priming, no priming effects were found with the repeated masked
      technique, and prime detection was poor but just above chance levels. We conclude
      that with repeated masked primes, there is effective visual masking but that
      associative priming and repetition priming do not occur with experiment-unique
      prime-target pairs. Explanations for this apparent discrepancy across priming
      paradigms are discussed. The priming stimuli and prime-target pairs used in this
      study may be downloaded as supplemental materials from mc.psychonomic
      journals.org/content/supplemental.

PMID- 19103981
TI  - Dexamethasone and GLP-2 given to lactating rat dams influence glucose uptake in
      suckling and postweanling offspring.
AB  - BACKGROUND: Glucagon-like peptide-2 (GLP-2) enhances intestinal absorption in
      adult animals. Glucocorticosteroids accelerate the ontogeny of the intestine and
      increase sugar uptake in adult animals. Modifying the maternal diet during
      lactation alters nutrient uptake in the offspring. The authors hypothesized that
      GLP-2 and dexamethasone, when administrated to lactating rat dams, enhance sugar
      uptake in the suckling and postweanling offspring. METHODS: Rat dams were treated
      during lactation with GLP-2 (0.1 microg/g/day subcutaneously [SC], twice daily),
      dexamethasone (0.128 microg/g/day SC, once daily), GLP-2 + dexamethasone (same
      doses), or placebo. The suckling offspring were sacrificed at 19-21 days of age,
      and the postweanlings were sacrificed 4 weeks later. Intestinal glucose and
      fructose uptake was assessed using an in vitro ring technique. RESULTS: GLP-2 and
      dexamethasone resulted in lower body weights, and dexamethasone caused intestinal
      atrophy in sucklings. The jejunal atrophy in sucklings given dexamethasone was
      prevented by GLP-2 + dexamethasone. In sucklings, the maximal transport rate and
      the Michaelis affinity constant for ileal glucose uptake were both increased by
      GLP-2 and GLP-2 + dexamethasone. In contrast, in postweanlings, the maximal
      transport rate for jejunal glucose uptake was reduced by dexamethasone and GLP-2,
      as was ileal fructose uptake. CONCLUSIONS: Treating lactating rat dams with GLP-2
      or dexamethasone enhances glucose uptake in sucklings, but the late effect is a
      reduction in glucose and fructose absorption in postweanlings. The nutritional
      significance of these findings remains to be established.

PMID- 19103982
TI  - The systematic development of a tailored e-mail intervention for health behavior
      change toward increasing intentional physical activity.
AB  - Although the benefits of physical activity are well known, most adults in the
      United States are relatively sedentary, with about 60% of adults not regularly
      physically active and 25% of those not active at all. This inactivity places the
      population at risk for many chronic diseases. Understanding optimal ways of both
      communicating with and educating employees regarding intention to reduce risk of
      ill health and enhance well-being through physical activity was the fundamental
      aim of this health communication research study. The authors designed a series of
      theory-based, tailored e-mail messages, which were evaluated for content validity
      by health care experts and focus groups. Focus groups were held according to the
      stage-of-change level of the participants, and two clear domains emerged:
      persuasion and decision domains. Improving societal well-being in a cost
      effective manner using e-mail remains to be seen; however, creating interventions
      to engineer sufficient impact on health behavior decision making is an investment
      worth exploring.

PMID- 19103983
TI  - Novel strategy to reduce sudden-death risk in the healing phase after myocardial
      infarction.

PMID- 19103984
TI  - Statins, central blood pressure, and blood pressure amplification.

PMID- 19103985
TI  - Improving adherence to guidelines for acute stroke management.

PMID- 19103986
TI  - Multimarker approach to evaluate correlates of vascular stiffness: the Framingham
      Heart Study.
AB  - BACKGROUND: Arterial stiffness increases with age and contributes to the
      pathogenesis of systolic hypertension and cardiovascular disease in the elderly.
      Knowledge about the pathophysiological processes that determine arterial
      stiffness may help guide therapeutic approaches. METHODS AND RESULTS: We related
      7 circulating biomarkers representing distinct biological pathways (C-reactive
      protein, aldosterone-to-renin ratio, N-terminal proatrial natriuretic peptide and
      B-type natriuretic peptide, plasminogen activator inhibitor-1, fibrinogen, and
      homocysteine) to 5 vascular function measures (central pulse pressure, carotid
      femoral pulse-wave velocity, mean arterial pressure, forward pressure wave
      amplitude [all measures of conduit artery stiffness], and augmented pressure, an
      indicator of wave reflection) in 2000 Framingham Offspring Study participants
      (mean age, 61 years; 55% women). Tonometry measures were obtained on average 3
      years after the biomarkers were measured. In multivariable linear regression
      models adjusting for covariates, the biomarker panel was significantly associated
      with all 5 vascular measures (P<0.003 for all). On backward elimination, the
      aldosterone-to-renin ratio was positively associated with each stiffness measure
      (P< or =0.002 for all). In addition, C-reactive protein was positively related to
      augmented pressure (P=0.0003), whereas plasminogen activator inhibitor-1 was
      positively associated with mean arterial pressure (P=0.003), central pulse
      pressure (P=0.001), and forward pressure wave (P=0.01). CONCLUSIONS: Our cross
      sectional data on a community-based sample suggest a distinctive pattern of
      positive associations of biomarkers of renin-angiotensin-aldosterone system
      activation with pan-arterial vascular stiffness, plasminogen activator inhibitor
      1 with central vascular stiffness indices, and C-reactive protein with wave
      reflection. These observations support the notion of differential influences of
      biological pathways on vascular stiffness measures.

PMID- 19103987
TI  - Activated endocannabinoid system in coronary artery disease and antiinflammatory
      effects of cannabinoid 1 receptor blockade on macrophages.
AB  - BACKGROUND: Cannabinoid 1 (CB1) receptor blockade with rimonabant represents a
      clinical therapeutic strategy for obesity. Recently, the role of the
      endocannabinoid system has been described in peripheral organs. We sought to
      determine whether the endocannabinoid system could be involved in human
      atherosclerosis and whether CB1 receptor blockade could modulate proinflammatory
      activity in macrophages. METHODS AND RESULTS: mRNA expression levels of CB1
      receptor in coronary atherectomy samples were significantly higher in patients
      with unstable angina than in those with stable angina (3.62+/-2.96-fold; n=7;
      P<0.05). Immunoreactive area analysis of the coronary artery showed that CB1
      receptor expression was greater in lipid-rich atheromatous plaques than in
      fibrous plaques, especially in CD68 macrophages (9.5+/-1.2% versus 0.6+/-0.6%;
      n=5; P<0.01). Levels of blood endocannabinoids were significantly higher in
      patients with coronary artery disease (n=20) than those without coronary artery
      disease (n=20) (median [interquartile range]: anandamide, 1.048 pmol/mL [0.687 to
      1.387 pmol/mL] versus 0.537 pmol/mL [0.468 to 0.857 pmol/mL], P<0.01; 2
      arachidonoyl glycerol, 13.30 pmol/mL [6.65 to 16.21 pmol/mL] versus 7.67 pmol/mL
      [6.39 to 10.03 pmol/mL], P<0.05). In cultured macrophages, expression of CB1
      receptor was significantly increased during monocyte-macrophage differentiation
      (1.78+/-0.13-fold; n=6; P<0.01). CB1 receptor blockade in macrophages induced a
      significant increase in cytosolic cAMP (29.9+/-13.0%; n=4; P<0.01), inhibited
      phosphorylation of c-Jun N-terminal kinase (-19.1+/-12.6%, n=4; P<0.05), and
      resulted in a significant decrease in the production of proinflammatory mediators
      (interleukin-1beta, -28.9+/-10.9%; interleukin-6, -24.8+/-7.6%; interleukin-8, 
      22.7+/-5.2%; tumor necrosis factor-alpha, -13.6+/-4.8%; matrix metalloproteinase
      9, -16.4+/-3.8%; n=4 to 8; P<0.01). CONCLUSIONS: Patients with coronary artery
      disease demonstrated the activation of the endocannabinoid system with elevated
      levels of blood endocannabinoids and increased expression of CB1 receptor in
      coronary atheroma. CB1 receptor blockade exhibited antiinflammatory effects on
      macrophages, which might provide beneficial effects on atherogenesis.

PMID- 19103988
TI  - Disparity in outcomes of surgical revascularization for limb salvage: race and
      gender are synergistic determinants of vein graft failure and limb loss.
AB  - BACKGROUND: Vein bypass surgery is an effective therapy for atherosclerotic
      occlusive disease in the coronary and peripheral circulations; however, long-term
      results are limited by progressive attrition of graft patency. Failure of vein
      bypass grafts in patients with critical limb ischemia results in morbidity, limb
      loss, and additional resource use. Although technical factors are known to be
      critical to the success of surgical revascularization, patient-specific risk
      factors are not well defined. In particular, the relationship of race/ethnicity
      and gender to the outcomes of peripheral bypass surgery has been controversial.
      METHODS AND RESULTS: We analyzed the Project of Ex Vivo Vein Graft Engineering
      via Transfection III (PREVENT III) randomized trial database, which included 1404
      lower extremity vein graft operations performed exclusively for critical limb
      ischemia at 83 North American centers. Trial design included intensive ultrasound
      surveillance of the bypass graft and clinical follow-up to 1 year. Multivariable
      modeling (Cox proportional hazards and propensity score) was used to examine the
      relationships of demographic variables to clinical end points, including
      perioperative (30-day) events and 1-year outcomes (vein graft patency, limb
      salvage, and patient survival). Final propensity score models adjusted for 16
      covariates (including type of institution, technical factors, selected
      comorbidities, and adjunctive medications) to examine the associations between
      race, gender, and outcomes. Among the 249 black patients enrolled in PREVENT III,
      118 were women and 131 were men. Black men were at increased risk for early graft
      failure (hazard ratio [HR], 2.832 for 30-day failure; 95% confidence interval
      [CI], 1.393 to 5.759; P=0.0004), even when the analysis was restricted to exclude
      high-risk venous conduits. Black patients experienced reduced secondary patency
      (HR, 1.49; 95% CI, 1.08 to 2.06; P=0.016) and limb salvage (HR, 2.02; 95% CI,
      1.27 to 3.20; P=0.003) at 1 year. Propensity score models demonstrate that black
      women were the most disadvantaged, with an increased risk for loss of graft
      patency (HR, 2.02 for secondary patency; 95% CI, 1.27 to 3.20; P=0.003) and major
      amputation (HR, 2.38; 95% CI, 1.18 to 4.83; P=0.016) at 1 year. Perioperative
      mortality and 1-year mortality were similar across race/gender groups.
      CONCLUSIONS: Black race and female gender are risk factors for adverse outcomes
      after vein bypass surgery for limb salvage. Graft failure and limb loss are more
      common events in black patients, with black women being a particularly high-risk
      group. These data suggest the possibility of an altered biological response to
      vein grafting in this population; however, further studies are needed to
      determine the mechanisms underlying these observed disparities in outcome.

PMID- 19103989
TI  - Epicardial border zone overexpression of skeletal muscle sodium channel SkM1
      normalizes activation, preserves conduction, and suppresses ventricular
      arrhythmia: an in silico, in vivo, in vitro study.
AB  - BACKGROUND: In depolarized myocardial infarct epicardial border zones, the
      cardiac sodium channel (SCN5A) is largely inactivated, contributing to low action
      potential upstroke velocity (V(max)), slow conduction, and reentry. We
      hypothesized that a fast inward current such as the skeletal muscle sodium
      channel (SkM1) operating more effectively at depolarized membrane potentials
      might restore fast conduction in epicardial border zones and be antiarrhythmic.
      METHODS AND RESULTS: Computer simulations were done with a modified Hund-Rudy
      model. Canine myocardial infarcts were created by coronary ligation. Adenovirus
      expressing SkM1 and green fluorescent protein or green fluorescent protein alone
      (sham) was injected into epicardial border zones. After 5 to 7 days, dogs were
      studied with epicardial mapping, programmed premature stimulation in vivo, and
      cellular electrophysiology in vitro. Infarct size was determined, and tissues
      were immunostained for SkM1 and green fluorescent protein. In the computational
      model, modest SkM1 expression preserved fast conduction at potentials as positive
      as -60 mV; overexpression of SCN5A did not. In vivo epicardial border zone
      electrograms were broad and fragmented in shams (31.5 +/- 2.3 ms) and narrower in
      SkM1 (22.6 +/- 2.8 ms; P=0.03). Premature stimulation induced ventricular
      tachyarrhythmia/fibrillation >60 seconds in 6 of 8 shams versus 2 of 12 SkM1
      (P=0.02). Microelectrode studies of epicardial border zones from SkM1 showed
      membrane potentials equal to that of shams and V(max) greater than that of shams
      as membrane potential depolarized (P<0.01). Infarct sizes were similar (sham, 30
      +/- 2.8%; SkM1, 30 +/- 2.6%; P=0.86). SkM1 expression in injected epicardium was
      confirmed immunohistochemically. CONCLUSIONS: SkM1 increases V(max) of
      depolarized myocardium and reduces the incidence of inducible sustained
      ventricular tachyarrhythmia/fibrillation in canine infarcts. Gene therapy to
      normalize activation by increasing V(max) at depolarized potentials may be a
      promising antiarrhythmic strategy.

PMID- 19103990
TI  - Randomized study of the crush technique versus provisional side-branch stenting
      in true coronary bifurcations: the CACTUS (Coronary Bifurcations: Application of
      the Crushing Technique Using Sirolimus-Eluting Stents) Study.
AB  - BACKGROUND: Sirolimus-eluting stents have been reported to be effective in the
      treatment of coronary bifurcations. Still, it has not been fully clarified which
      strategy would provide the best results with true bifurcation lesions. METHODS
      AND RESULTS: The CACTUS trial (Coronary bifurcations: Application of the Crushing
      Technique Using Sirolimus-eluting stents) is a prospective, randomized,
      multicenter study comparing 2 different techniques of stenting, with mandatory
      final kissing-balloon inflation, in true bifurcations: (1) elective "crush"
      stenting and (2) stenting of only the main branch, with provisional side-branch T
      stenting. From August 2004 to June 2007, 350 patients were enrolled in 12
      European centers. The primary angiographic end point was the in-segment
      restenosis rate, and the primary clinical end point was the occurrence of major
      adverse cardiac events (cardiac death, myocardial infarction, or target-vessel
      revascularization) at 6 months. At 6 months, angiographic restenosis rates were
      not different between the crush group (4.6% and 13.2% in the main branch and side
      branch, respectively) and the provisional stenting group (6.7% and 14.7% in the
      main branch and side branch, respectively; P=NS). Additional stenting on the side
      branch in the provisional stenting group was required in 31% of lesions. Rates of
      major adverse cardiac events were also similar in the 2 groups (15.8% in the
      crush group versus 15% in the provisional stenting group, P=NS). CONCLUSIONS: In
      most bifurcations with a significant stenosis in both branches, a provisional
      strategy of stenting the main branch only is effective, with the need to implant
      a second stent on the side branch occurring in approximately one third of cases.
      The implantation of 2 stents does not appear to be associated with a higher
      incidence of adverse events at 6 months.

PMID- 19103991
TI  - Body mass index and vigorous physical activity and the risk of heart failure
      among men.
AB  - BACKGROUND: Elevated body mass index (BMI; weight in kilograms divided by height
      in meters squared) in the obese range (> or =30 kg/m(2)) is associated with an
      excess risk of heart failure (HF). However, the impact of overweight or preobese
      (BMI, 25 to 29.9 kg/m(2)) status and physical activity on HF risk is unclear.
      METHODS AND RESULTS: In a prospective cohort of 21,094 men (mean age, 53 years)
      without known coronary heart disease at baseline in the Physicians' Health Study,
      we examined the individual and combined effects of BMI and vigorous physical
      activity (exercise to the point of breaking a sweat) on HF incidence from 1982 to
      2007. We evaluated BMI as both a continuous (per 1-kg/m(2) increment) and a
      categorical (lean, <25 kg/m(2); overweight, 25 to 29.9 kg/m(2); and obese, > or
      =30 kg/m(2)) variable; we evaluated vigorous physical activity primarily as a
      dichotomous variable (inactive [rarely/never] versus active [> or =1 to 3 times a
      month]). During follow-up (mean, 20.5 years), 1109 participants developed new
      onset HF. In multivariable analyses, every 1-kg/m(2) increase in BMI was
      associated with an 11% (95% confidence interval [CI], 9 to 13) increase in HF
      risk. Compared with lean participants, overweight participants had a 49% (95% CI,
      32 to 69) and obese participants had a 180% (95% CI, 124 to 250) increase in HF
      risk. Vigorous physical activity conferred an 18% (95% CI, 4 to 30) decrease in
      HF risk. No interaction was found between BMI and vigorous physical activity and
      HF risk (P=0.96). Lean active men had the lowest and obese inactive men had the
      highest risk of HF. Compared with lean active men, the hazard ratios were 1.19
      (95% CI, 0.94 to 1.51), 1.49 (95% CI, 1.30 to 1.71), 1.78 (95% CI, 1.43 to 2.23),
      2.68 (95% CI, 2.08 to 3.45), and 3.93 (95% CI, 2.60 to 5.96) in lean inactive,
      overweight active, overweight inactive, obese active, and obese inactive men,
      respectively. CONCLUSIONS: In this cohort of men, elevated BMI, even in the
      preobese range, was associated with an increased risk of HF, and vigorous
      physical activity was associated with a decreased risk. Public health measures to
      curtail excess weight, to maintain optimal weight, and to promote physical
      activity may limit the scourge of HF.

PMID- 19103992
TI  - Myocardial adeno-associated virus serotype 6-betaARKct gene therapy improves
      cardiac function and normalizes the neurohormonal axis in chronic heart failure.
AB  - BACKGROUND: The upregulation of G protein-coupled receptor kinase 2 in failing
      myocardium appears to contribute to dysfunctional beta-adrenergic receptor
      (betaAR) signaling and cardiac function. The peptide betaARKct, which can inhibit
      the activation of G protein-coupled receptor kinase 2 and improve betaAR
      signaling, has been shown in transgenic models and short-term gene transfer
      experiments to rescue heart failure (HF). This study was designed to evaluate
      long-term betaARKct expression in HF with the use of stable myocardial gene
      delivery with adeno-associated virus serotype 6 (AAV6). METHODS AND RESULTS: In
      HF rats, we delivered betaARKct or green fluorescent protein as a control via
      AAV6-mediated direct intramyocardial injection. We also treated groups with
      concurrent administration of the beta-blocker metoprolol. We found robust and
      long-term transgene expression in the left ventricle at least 12 weeks after
      delivery. betaARKct significantly improved cardiac contractility and reversed
      left ventricular remodeling, which was accompanied by a normalization of the
      neurohormonal (catecholamines and aldosterone) status of the chronic HF animals,
      including normalization of cardiac betaAR signaling. Addition of metoprolol
      neither enhanced nor decreased betaARKct-mediated beneficial effects, although
      metoprolol alone, despite not improving contractility, prevented further
      deterioration of the left ventricle. CONCLUSIONS: Long-term cardiac AAV6
      betaARKct gene therapy in HF results in sustained improvement of global cardiac
      function and reversal of remodeling at least in part as a result of a
      normalization of the neurohormonal signaling axis. In addition, betaARKct alone
      improves outcomes more than a beta-blocker alone, whereas both treatments are
      compatible. These findings show that betaARKct gene therapy can be of long-term
      therapeutic value in HF.

PMID- 19103993
TI  - Acute doxorubicin cardiotoxicity is associated with p53-induced inhibition of the
      mammalian target of rapamycin pathway.
AB  - BACKGROUND: Doxorubicin is used to treat childhood and adult cancer. Doxorubicin
      treatment is associated with both acute and chronic cardiotoxicity. The
      cardiotoxic effects of doxorubicin are cumulative, which limits its
      chemotherapeutic dose. Free radical generation and p53-dependent apoptosis are
      thought to contribute to doxorubicin-induced cardiotoxicity. METHODS AND RESULTS:
      Adult transgenic (MHC-CB7) mice expressing cardiomyocyte-restricted dominant
      interfering p53 and their nontransgenic littermates were treated with doxorubicin
      (20 mg/kg cumulative dose). Nontransgenic mice exhibited reduced left ventricular
      systolic function (predoxorubicin fractional shortening [FS] 61+/-2%,
      postdoxorubicin FS 45+/-2%, mean+/-SEM, P<0.008), reduced cardiac mass, and high
      levels of cardiomyocyte apoptosis 7 days after the initiation of doxorubicin
      treatment. In contrast, doxorubicin-treated MHC-CB7 mice exhibited normal left
      ventricular systolic function (predoxorubicin FS 63+/-2%, postdoxorubicin FS 60+/
      2%, P>0.008), normal cardiac mass, and low levels of cardiomyocyte apoptosis.
      Western blot analyses indicated that mTOR (mammalian target of rapamycin)
      signaling was inhibited in doxorubicin-treated nontransgenic mice but not in
      doxorubicin-treated MHC-CB7 mice. Accordingly, transgenic mice with cardiomyocyte
      restricted, constitutively active mTOR expression (MHC-mTORca) were studied. Left
      ventricular systolic function (predoxorubicin FS 64+/-2%, postdoxorubicin FS 60+/
      3%, P>0.008) and cardiac mass were normal in doxorubicin-treated MHC-mTORca mice,
      despite levels of cardiomyocyte apoptosis similar to those seen in doxorubicin
      treated nontransgenic mice. CONCLUSIONS: These data suggest that doxorubicin
      treatment induces acute cardiac dysfunction and reduces cardiac mass via p53
      dependent inhibition of mTOR signaling and that loss of myocardial mass, and not
      cardiomyocyte apoptosis, is the major contributor to acute doxorubicin
      cardiotoxicity.

PMID- 19103994
TI  - Critical role of transcription factor cyclic AMP response element modulator in
      beta1-adrenoceptor-mediated cardiac dysfunction.
AB  - BACKGROUND: Chronic stimulation of the beta(1)-adrenoceptor (beta(1)AR) plays a
      crucial role in the pathogenesis of heart failure; however, underlying mechanisms
      remain to be elucidated. The regulation by transcription factors cAMP response
      element-binding protein (CREB) and cyclic AMP response element modulator (CREM)
      represents a fundamental mechanism of cyclic AMP-dependent gene control possibly
      implicated in beta(1)AR-mediated cardiac deterioration. METHODS AND RESULTS: We
      studied the role of CREM in beta(1)AR-mediated cardiac effects, comparing
      transgenic mice with heart-directed expression of beta(1)AR in the absence and
      presence of functional CREM. CREM inactivation protected from cardiomyocyte
      hypertrophy, fibrosis, and left ventricular dysfunction in beta(1)AR
      overexpressing mice. Transcriptome and proteome analysis revealed a set of
      predicted CREB/CREM target genes including the cardiac ryanodine receptor,
      tropomyosin 1alpha, and cardiac alpha-actin as altered on the mRNA or protein
      level along with the improved phenotype in CREM-deficient beta(1)AR-transgenic
      hearts. CONCLUSIONS: The results imply the regulation of genes by CREM as an
      important mechanism of beta(1)AR-induced cardiac damage in mice.

PMID- 19103996
TI  - Platelet P2Y(12) receptor influences the vessel wall response to arterial injury
      and thrombosis.
AB  - BACKGROUND: Platelets are believed to play an important role in atherogenesis and
      the vessel response to vascular injury. The P2Y(12) receptor (P2Y(12)) plays a
      central role in amplifying platelet aggregation, dense granule and alpha-granule
      secretion, P-selectin expression, microparticle formation, and procoagulant
      membrane changes, regardless of the activating stimulus. We hypothesized that
      P2Y(12) deficiency might reduce the vessel wall response to vascular injury as
      well as thrombosis in murine vascular injury models. METHODS AND RESULTS: P2Y(12)
      deficient (-/-) mice and littermate controls (+/+) were bred on a C57 BL/6
      background. In vivo murine models of arterial injury were employed alone and in
      combination with bone marrow transplantation to investigate the role of P2Y(12)
      in the vessel wall response to arterial injury and thrombosis. At 21 days after
      ferric chloride injury, neointima formation in P2Y(12)(-/-) arteries was
      significantly less than that observed in control strain arteries (P<0.025). In
      agreement with this, the intima-media ratio was significantly greater in femoral
      wire-injured arteries from P2Y(12)(+/+) compared with P2Y(12)(-/-) animals
      (P<0.05). Bone marrow transplantation was used to examine the importance of
      vessel wall P2Y(12) versus platelet P2Y(12). Analysis of arterial sections from
      chimeric animals at 21 days after injury revealed a smaller intima-media ratio in
      -/- to +/+ animals than in the positive (+/+ to +/+) control group (P<0.01).
      CONCLUSIONS: These data demonstrate a role for platelet P2Y(12) in the vessel
      wall response to arterial injury and thrombosis. This illustrates the manner in
      which platelets may contribute to atherogenesis and restenosis.

PMID- 19103997
TI  - Dysregulation of vascular TRPM7 and annexin-1 is associated with endothelial
      dysfunction in inherited hypomagnesemia.
AB  - Inadequate magnesium intake and hypomagnesemia may contribute to chronic
      diseases, such as hypertension. The novel magnesium transporter TRPM7 is a
      critical regulator of magnesium homeostasis in vascular cells, but its role in
      pathophysiology is unclear. In a model of hypomagnesemia, we examined
      microvascular structure and function, TRPM7 expression, and vascular inflammatory
      status using inbred mice selected for normal-high intracellular magnesium levels
      or low intracellular magnesium levels (MgLs). Blood pressure was significantly
      increased in MgLs compared with normal-high intracellular magnesium levels.
      Pressurized myography of mesenteric resistance arteries showed that MgLs had
      significantly impaired endothelial function together with decreased plasma
      nitrate levels and endothelial NO synthase expression when compared with normal
      high intracellular magnesium levels. Significant differences in vascular
      structure were also evident in both mesenteric arteries and aortas from MgLs.
      Aortas from MgLs had increased medial cross-sectional areas, whereas mesenteric
      arteries from MgLs had increased lumen diameters with increased medial cross
      sectional areas, indicating outward hypertrophic remodeling. Expression of the
      magnesium transporter TRPM7 was significantly elevated in the vasculature of
      MgLs, whereas expression of a TRPM7 downstream target, the anti-inflammatory
      molecule annexin-1, was reduced. MgLs had increased expression of vascular cell
      adhesion molecule-1 and plasminogen activator inhibitor-1, indicating vascular
      inflammation. Taken together, these data demonstrate that the inherited magnesium
      status of MgLs and normal-high intracellular magnesium levels mice affects
      magnesium transporter expression, endothelial function, vascular structure, and
      inflammation. Our findings suggest a potential regulatory role for TRPM7
      signaling in the maintenance of vascular integrity. Alterations in magnesium
      status and/or TRPM7 signaling may contribute to vascular injury in conditions
      associated with hypomagnesemia.

PMID- 19103995
TI  - Impact of statin therapy on central aortic pressures and hemodynamics: principal
      results of the Conduit Artery Function Evaluation-Lipid-Lowering Arm (CAFE-LLA)
      Study.
AB  - BACKGROUND: Statins reduce the risk of cardiovascular events in people with
      hypertension. This benefit could arise from a beneficial effect of statins on
      central aortic pressures and hemodynamics. The Conduit Artery Function Evaluation
      Lipid-Lowering Arm (CAFE-LLA) study, an Anglo-Scandinavian Cardiac Outcomes Trial
      (ASCOT) substudy, investigated this hypothesis in a prospective placebo
      controlled study of treated patients with hypertension. METHODS AND RESULTS: CAFE
      LLA recruited 891 patients randomized to atorvastatin 10 mg/d or placebo from 5
      centers in the United Kingdom and Ireland. Radial artery applanation tonometry
      and pulse-wave analysis were used to derive central aortic pressures and
      hemodynamic indices at repeated visits over 3.5 years of follow-up. Atorvastatin
      lowered low-density lipoprotein cholesterol by 32.4 mg/dL (95% confidence
      interval [CI], 28.6 to 36.3) and total cholesterol by 35.1 mg/dL (95% confidence
      interval, 30.9 to 39.4) relative to placebo. Time-averaged brachial blood
      pressure was similar in CAFE-LLA patients randomized to atorvastatin or placebo
      (change in brachial systolic blood pressure, -0.1 mm Hg [95% CI, -1.8 to 1.6],
      P=0.9; change in brachial pulse pressure, -0.02 mm Hg [95% CI, -1.6 to 1.6],
      P=0.9). Atorvastatin did not influence central aortic pressures (change in aortic
      systolic blood pressure, -0.5 mm Hg [95% CI, -2.3 to 1.2], P=0.5; change in
      aortic pulse pressure, -0.4 mm Hg [95% CI, -1.9 to 1.0], P=0.6) and had no
      influence on augmentation index (change in augmentation index, -0.4%; 95% CI, 
      1.7 to 0.8; P=0.5) or heart rate (change in heart rate, 0.25 bpm; 95% CI, -1.3 to
      1.8; P=0.7) compared with placebo. The effect of statin or placebo therapy was
      not modified by the blood pressure-lowering treatment strategy in the factorial
      design. CONCLUSIONS: Statin therapy sufficient to significantly reduce
      cardiovascular events in treated hypertensive patients in ASCOT did not influence
      central aortic blood pressure or hemodynamics in a large representative cohort of
      ASCOT patients in CAFE-LLA.

PMID- 19103998
TI  - Hypertension and sex differences in the age-related renal changes when
      cyclooxygenase-2 activity is reduced during nephrogenesis.
AB  - Several studies have proposed that cyclooxygenase-2 (COX2) is involved in the
      regulation of nephrogenesis and that an impaired nephrogenesis may induce the
      development of hypertension. This study was designed to test the hypothesis that
      the decrease of COX2 activity leads to a reduction in nephron number, an increase
      in arterial pressure, and age-dependent renal alterations that are greater in
      male than in female rats. Arterial pressure was measured from the first to the
      16th month of life in rats treated with vehicle or a COX2 inhibitor during the
      nephrogenic period. Stereological and histological evaluations and renal function
      studies were performed at different ages. Arterial pressure increased (14%;
      P<0.05) and nephron number decreased (17%; P<0.05) to similar levels in male and
      female COX2-treated rats. However, glomerular filtration rate (31%) and renal
      plasma flow (25%) decreased (P<0.05) in male but not in female COX2-treated rats.
      A greater (P<0.05) age-dependent elevation in glomerular hypertrophy was also
      found in male COX2-treated rats compared with their female littermates.
      Glomerulosclerosis and tubulointerstitial damage in renal cortex and medulla were
      also significantly enhanced in male but not in female aged COX2-treated rats. Our
      results demonstrate that the decrease in COX2 activity during renal development
      leads to a reduction in nephron number and to an elevation in arterial pressure
      that are similar in males and females. However, the consequent age-dependent
      deterioration of the renal structure and renal function is only significantly
      enhanced in male rats.

PMID- 19103999
TI  - Leptin signaling in the nucleus tractus solitarii increases sympathetic nerve
      activity to the kidney.
AB  - The hypothalamic arcuate nucleus was initially regarded as the principal site of
      leptin action, but there is increasing evidence for functional leptin receptors
      in extrahypothalamic sites, including the nucleus tractus solitarii (NTS). We
      demonstrated previously that arcuate injection of leptin increases sympathetic
      nerve activity (SNA) to brown adipose tissue and kidney. In this study, we tested
      the hypothesis that leptin signaling in the NTS affects sympathetic neural
      outflow. Using a stereotaxic device in anesthetized rats, we microinjected leptin
      (0.25 to 1.00 microg) or saline into the NTS while recording SNA to kidney and
      brown adipose tissue. Microinjection of leptin into the commissural and medial
      subnuclei of the caudal NTS at the level of the area postrema in Sprague-Dawley
      rats produced a dose-related increase in renal SNA (+112+/-15% with leptin 1
      microg; n=7; P<0.001) but did not increase SNA to brown adipose tissue (-15+/
      12%; P value not significant). This effect depended on intact functional leptin
      receptors, because it was not observed in Zucker obese rats that have a missense
      mutation in the leptin receptor. Rostral NTS injection of leptin failed to
      increase SNA, indicating that leptin signaling in the NTS is probably confined to
      the caudal NTS at the level of the area postrema. In summary, this study
      demonstrates that leptin signaling in the caudal NTS increases SNA to the kidney
      but not to the brown adipose tissue. The study strengthens the concept of a
      distributed brain network of leptin action and demonstrates that these
      distributed brain sites can mediate contrasting sympathetic responses to leptin.

PMID- 19104000
TI  - Obesity increases blood pressure, cerebral vascular remodeling, and severity of
      stroke in the Zucker rat.
AB  - Obesity is a risk factor for stroke, but the mechanisms by which obesity
      increases stroke risk are unknown. Because microvascular architecture contributes
      to the outcome of stroke, we hypothesized that middle cerebral arteries (MCAs)
      from obese Zucker rats (OZRs) undergo inward remodeling and develop increased
      myogenic tone compared with those in lean Zucker rats (LZRs). We further
      hypothesized that OZRs have an increased infarct after cerebral ischemia and that
      changes in vascular structure and function correlate with the development of
      hypertension in OZRs. Blood pressure was measured by telemetry in LZRs and OZRs
      from 6 to 17 weeks of age. Vessel structure and function were assessed in
      isolated MCAs. Stroke damage was assessed after ischemia was induced for 60
      minutes followed by 24 hours of reperfusion. Although mean arterial pressure was
      similar between young rats (6 to 8 weeks old), mean arterial pressure was higher
      in adult (14 to 17 weeks old) OZRs than in LZRs. MCAs from OZRs had a smaller
      lumen diameter and increased myogenic vasoconstriction compared with those from
      LZRs. After ischemia, infarction was 58% larger in OZRs than in LZRs. Before the
      development of hypertension, MCA myogenic reactivity and lumen diameter, as well
      as infarct size, were similar between young LZRs and OZRs. Our results indicate
      that the MCAs of OZRs undergo structural remodeling and that these rats have
      greater cerebral injury after cerebral ischemia. These cerebrovascular changes
      correlate with the development of hypertension and suggest that the increased
      blood pressure may be the major determinant for stroke risk in obese individuals.

PMID- 19104001
TI  - Contribution of endothelin A receptors in endothelin 1-dependent natriuresis in
      female rats.
AB  - Renal medullary endothelin B receptors contribute to blood pressure regulation by
      facilitating salt excretion. Premenopausal females have relatively less
      hypertension than males; therefore, we examined whether there is a sex difference
      in the natriuretic response to renal medullary infusion of endothelin peptides in
      the rat. All of the experiments were conducted in anesthetized wild-type (wt) or
      endothelin B-deficient (sl/sl) rats. Infusion of endothelin 1 (ET-1)
      significantly increased sodium excretion (U(Na)V) in female, but not male, wt
      rats (Delta U(Na)V: 0.41+/-0.07 versus -0.04+/-0.06 micromol/min, respectively).
      The endothelin B receptor agonist sarafotoxin 6c produced similar increases in
      U(Na)V in both male (Delta 0.58+/-0.15 micromol/min) and female (Delta 0.67+/
      0.18 micromol/min) wt rats. Surprisingly, ET-1 markedly increased U(Na)V in
      female (Delta 0.70+/-0.11 micromol/min) but not male sl/sl rats (Delta 0.00+/
      0.05 micromol/min). ET-1 had no effect on medullary blood flow in females,
      although medullary blood flow was significantly reduced to a similar extent in
      males of both strains. These results suggest that the lack of a natriuretic
      response to ET-1 in male rats is because of reductions in medullary blood flow.
      Treatment with ABT-627, an endothelin A receptor antagonist, or N(G)-propyl-L
      arginine, an NO synthase 1 inhibitor, prevented the increase in U(Na)V observed
      in female rats. Gonadectomy eliminated the sex difference in the U(Na)V and
      medullary blood flow response to ET-1. These findings demonstrate that there is
      no sex difference in endothelin B-dependent natriuresis, and the endothelin A
      receptor contributes to ET-1-dependent natriuresis in female rats, an effect that
      requires NO synthase 1. These findings provide a possible mechanism for why
      premenopausal women are more resistant to salt-dependent hypertension.

PMID- 19104002
TI  - A new role for caveolin-1: regulation of guanosine triphosphate cyclohydrolase I
      and tetrahydrobiopterin in endothelial cells.

PMID- 19104003
TI  - Increased lectin-like oxidized low-density lipoprotein receptor-1 expression in
      the maternal vasculature of women with preeclampsia: role for peroxynitrite.
AB  - Preeclampsia is a hypertensive disorder unique to pregnancy, in which the
      placenta may release factors into the maternal circulation resulting in systemic
      effects. Small dense low-density lipoprotein (LDL; which is susceptible for
      oxidation) is increased in preeclampsia. Lectin-like oxidized LDL receptor-1 (LOX
      1) is a receptor for oxidized LDL. However, the expression levels and the
      regulation of LOX-1 in the maternal vasculature of women with preeclampsia are
      unknown. We hypothesized that there is an increased LOX-1 expression in arteries
      from women with preeclampsia. We further hypothesized that circulating factors in
      the plasma of women with preeclampsia would upregulate the LOX-1 expression in
      vascular endothelial cells and contribute to vascular endothelial oxidative
      stress. We observed abundant LOX-1 expression and the presence of oxidized LDL in
      arteries from women with preeclampsia, which was negligible in arteries from
      normotensive pregnant women. Human umbilical vein endothelial cells treated for
      24 hours with 2% plasma from preeclamptic women increased LOX-1 expression and
      oxidized LDL uptake, as well as induced oxidative stress, as evidenced by
      increased NADPH oxidase activity and superoxide and peroxynitrite levels. These
      effects were significantly reduced by pretreatment with blocking antibody or
      small interfering RNA to LOX-1, as well as 5,10,15,20-tetrakis(4
      sulfonatophenyl)porphyrinato iron (III), chloride (FeTPPS), a peroxynitrite
      scavenger. Exogenous peroxynitrite and 3-morpholino sydnonimine (SIN-1) increased
      LOX-1 protein and mRNA expression. In conclusion, increased LOX-1 expression in
      the systemic vasculature of preeclampsia women provides a fundamental insight
      into the pathology of preeclampsia and likely contributes to the induction and
      maintenance of vascular oxidative stress.

PMID- 19104004
TI  - Pravastatin for cardiovascular event primary prevention in patients with mild-to
      moderate hypertension in the Management of Elevated Cholesterol in the Primary
      Prevention Group of Adult Japanese (MEGA) Study.
AB  - Lipid-lowering therapy in individuals with high risk of cardiovascular disease
      reduces the incidence of coronary heart disease. However, few studies have
      assessed the benefits of cholesterol lowering for primary prevention of coronary
      heart disease in hypertensive patients with mild dyslipidemia or without
      conventional dyslipidemia. The large, randomized Management of Elevated
      Cholesterol in the Primary Prevention Group of Adult Japanese Study showed a 33%
      reduction in coronary heart disease incidence with pravastatin as the primary
      prevention in Japanese patients. We conducted an exploratory analysis of the
      effect of diet plus pravastatin therapy on the primary prevention of
      cardiovascular events (coronary heart disease, coronary heart disease plus
      cerebral infarction, and cardiovascular disease) in the 3277 patients with
      hypertension during the 5-year follow-up. There were no significant differences
      in mean baseline total cholesterol, blood pressure levels, or variation in blood
      pressure during the 5-year period between the diet (n=1664) and diet plus
      pravastatin (n=1613) groups. In the diet plus pravastatin group, the relative
      risk of coronary heart disease plus cerebral infarction was reduced by 35%
      (hazard ratio: 0.65; CI: 0.46 to 0.93; P=0.02), cerebral infarction by 46%
      (hazard ratio: 0.54; CI: 0.29 to 0.98; P=0.04), and cardiovascular disease by 33%
      (hazard ratio: 0.67; CI: 0.49 to 0.91; P=0.01). In patients without a history of
      cardiovascular disease who have hypertension and mildly elevated cholesterol,
      pravastatin was effective in reducing the incidence of cardiovascular disease,
      particularly cerebral infarction. Hence, in patients with hypertension with
      mildly elevated cholesterol levels, treatment with a statin is advisable to
      reduce the burden of cardiovascular disease.

PMID- 19104005
TI  - The pump, the exchanger, and endogenous ouabain: signaling mechanisms that link
      salt retention to hypertension.

PMID- 19104006
TI  - Stress-induced sodium excretion: a new intermediate phenotype to study the early
      genetic etiology of hypertension?
AB  - Impaired stress-induced pressure natriuresis, ie, an inadequate compensatory
      increase in urinary sodium excretion (U(Na)V) in response to a stress-induced
      blood pressure increase, may lead to the premature development of essential
      hypertension. To assess the heritability of baseline U(Na)V, stress U(Na)V, and
      the U(Na)V response to stress (Delta U(Na)V=stress U(Na)V- baseline U(Na)V), we
      studied 396 black and 494 white twins, including monozygotic and dizygotic twins
      of the same as well as the opposite sex (mean age: 17.6+/-3.3 years; range: 11.9
      to 30.0 years). Bivariate genetic model fitting was performed to examine the
      extent to which genetic and environmental factors are common or specific to
      baseline and stress U(Na)V. Heritability estimates for Delta U(Na)V can be
      derived from these bivariate models. All of the bivariate analyses were performed
      separately in whites and blacks, because univariate models for baseline U(Na)V
      showed significant ethnic differences in heritability estimates. Best-fitting
      models showed that the heritability of stress U(Na)V was 0.42 in whites and 0.58
      in blacks. Only 15% and 11% of the total variance could be attributed to genetic
      factors common to baseline and stress U(Na)V in whites and blacks, respectively.
      After removal of all of the shared influences with baseline U(Na)V,
      heritabilities for stress U(Na)V were 0.32 in whites and 0.57 in blacks.
      Heritability estimates for Delta U(Na)V were 0.36 in whites and 0.39 in blacks.
      In summary, this study establishes Delta U(Na)V and stress U(Na)V as heritable
      phenotypes that may be used to study the genetic etiology of early hypertension
      development.

PMID- 19104007
TI  - Guanosine triphosphate cyclohydrolase I expression and enzymatic activity are
      present in caveolae of endothelial cells.
AB  - Tetrahydrobiopterin is an essential cofactor required for the synthesis of NO.
      GTP cyclohydrolase I (GTPCH I) is the rate-limiting enzyme for
      tetrahydrobiopterin production in endothelial cells, yet little is known about
      the subcellular localization of this enzyme. In this study, we demonstrated that
      GTPCH I is localized to caveolar membrane microdomains along with caveolin-1 and
      endothelial NO synthase. GTPCH I activity was detected in isolated caveolar
      membranes from cultured endothelial cells. Confocal and electron microscopy
      analyses confirmed GTPCH I colocalization with caveolin-1. Consistent with in
      vitro studies, GTPCH I activity was evident in isolated caveolar microdomains
      from lung homogenates of wild-type mice. Importantly, a 2-fold increase in GTPCH
      I activity was detected in the aortas of caveolin-1-deficient mice, suggesting
      that caveolin-1 may be involved in the control of GTPCH I enzymatic activity.
      Indeed, overexpression of caveolin-1 inhibits GTPCH I activity, and
      tetrahydrobiopterin biosynthesis is activated by the disruption of caveolae
      structure. These studies demonstrate that GTPCH I is targeted to caveolae
      microdomains in vascular endothelial cells, and tetrahydrobiopterin production
      occurs in close proximity to endothelial NO synthase. In addition, our findings
      provide new insights into the regulation of GTPCH I activity by the caveolar coat
      protein, caveolin-1.

PMID- 19104008
TI  - Praziquantel affects the regulatory myosin light chain of Schistosoma mansoni.
AB  - Praziquantel (PZQ) is the drug of choice for schistosomiasis and probably is the
      only highly effective drug currently available for treating schistosomiasis
      infected individuals. The mode of action of PZQ involves increasing the calcium
      uptake of the parasite, resulting in tegumental damage and death of the parasite.
      Despite its remarkable function, the target of PZQ has not been identified yet.
      To begin to understand where PZQ acts, in this study we expressed the cDNA
      library of Schistosoma mansoni on the surface of T7 bacteriophages and screened
      this library with labeled PZQ. This procedure identified a clone that strongly
      bound to PZQ. Subsequent DNA analysis of inserts showed that the clone coded for
      regulatory myosin light chain protein. The gene was then cloned, and recombinant
      S. mansoni myosin light chain (SmMLC) was expressed. Immunoblot analysis using
      antibodies raised to recombinant SmMLC (rSmMLC) showed that SmMLC is abundantly
      expressed in schistosomula and adult stages compared to the amount in cercarial
      stages. In vitro analyses also confirmed that PZQ strongly binds to rSmMLC.
      Further, peptide mapping studies showed that PZQ binds to amino acids 46 to 76 of
      SmMLC. Immunoprecipitation analysis confirmed that SmMLC is phosphorylated in
      vivo upon exposure to PZQ. Interestingly, significant levels of anti-SmMLC
      antibodies were present in vaccinated mice compared to the amount in infected
      mice, suggesting that SmMLC may be a potential target for protective immunity in
      schistosomiasis. These findings suggest that PZQ affects SmMLC function, and this
      may have a role in PZQ action.

PMID- 19104009
TI  - Identification by genomic and genetic analysis of two new genes playing a key
      role in intermediate glycopeptide resistance in Staphylococcus aureus.
AB  - Endogenous, low-level glycopeptide resistance in Staphylococcus aureus results
      from multifactorial genetic changes. Comparative genomic hybridization analysis
      revealed the specific deletion of a 1.8-kb segment encompassing two adjacent open
      reading frames (ORFs) of unknown function in a teicoplanin-susceptible revertant
      (strain 14-4rev) compared to the sequence of its isogenic, teicoplanin-resistant
      parental strain, strain 14-4. This provocative finding prompted us to perform a
      detailed genetic analysis of the contribution of this genomic segment to
      glycopeptide resistance. Despite repeated efforts in our laboratory, 14-4 and 14
      4rev have proven refractory to most genetic manipulations. To circumvent this
      difficulty, we evaluated the contribution of both putative ORFs (designated
      teicoplanin resistance factors trfA and trfB) on teicoplanin resistance in a
      different, genetically tractable background. Genetic analysis showed that single
      or double trfA and/or trfB mutations abolished teicoplanin resistance in two
      independent teicoplanin-resistant derivatives of NCTC8325 strain ISP794 generated
      by two-step passages with the drug. The frequency of teicoplanin-resistant
      mutants was markedly decreased by the absence of trfAB in the teicoplanin
      susceptible ISP794 background. Nevertheless, a low rate of teicoplanin-resistant
      mutants was selected from ISP794 trfAB, thus indicating an additional
      contribution of trfAB-independent pathways in the emergence of low-level
      glycopeptide resistance. Further experiments performed with clinical glycopeptide
      intermediate S. aureus isolate NRS3 indicated that the trfAB mutation could
      affect not only teicoplanin resistance but also vancomycin and oxacillin
      resistance. In conclusion, our study demonstrates the key role of two novel loci
      in endogenous, low-level glycopeptide resistance in S. aureus whose precise
      molecular functions warrant further investigation.

PMID- 19104010
TI  - Preclinical evaluation of GS-9160, a novel inhibitor of human immunodeficiency
      virus type 1 integrase.
AB  - GS-9160 is a novel and potent inhibitor of human immunodeficiency virus type 1
      (HIV-1) integrase (IN) that specifically targets the process of strand transfer.
      It is an authentic inhibitor of HIV-1 integration, since treatment of infected
      cells results in an elevation of two-long terminal repeat circles and a decrease
      of integration junctions. GS-9160 has potent and selective antiviral activity in
      primary human T lymphocytes producing a 50% effective concentration (EC(50)) of
      approximately 2 nM, with a selectivity index (50% cytotoxic concentration/EC(50))
      of approximately 2,000. The antiviral potency of GS-9160 decreased by 6- to 10
      fold in the presence of human serum. The antiviral activity of GS-9160 is
      synergistic in combination with representatives from three different classes of
      antiviral drugs, namely HIV-1 protease inhibitors, nonnucleoside reverse
      transcriptase inhibitors, and nucleotide reverse transcriptase inhibitors. Viral
      resistance selections performed with GS-9160 yielded a novel pattern of mutations
      within the catalytic core domain of IN; E92V emerged initially, followed by L74M.
      While E92V as a single mutant conferred 12-fold resistance against GS-9160, L74M
      had no effect as a single mutant. Together, these mutations conferred 67-fold
      resistance to GS-9160, indicating that L74M may potentiate the resistance caused
      by E92V. The pharmacokinetic profile of GS-9160 in healthy human volunteers
      revealed that once-daily dosing was not likely to achieve antiviral efficacy;
      hence, the clinical development of this compound was discontinued.

PMID- 19104011
TI  - Effects of zidovudine and stavudine on mitochondrial DNA of differentiating 3T3
      F442a cells are not associated with imbalanced deoxynucleotide pools.
AB  - To test whether zidovudine (3'-azido-3'-deoxythymidine) (AZT) inhibition of
      thymidine phosphorylation causes depletion of the TTP pool resulting in
      mitochondrial DNA depletion, 3T3-F442a cells were differentiated in the presence
      of AZT and analyzed to determine mitochondrial DNA content and deoxynucleotide
      levels. These results suggest that AZT toxicity may not be related to
      deoxynucleotide pool alterations.

PMID- 19104012
TI  - Association between antimicrobial consumption and resistance in Escherichia coli.
AB  - During a 9-year study period from 1997 through 2005, the association between
      antimicrobial resistance rates in Escherichia coli and outpatient antimicrobial
      consumption was investigated in 20 hospital districts in Finland. A total of
      754,293 E. coli isolates, mainly from urine samples, were tested for
      antimicrobial resistance in 26 clinical microbiology laboratories. The following
      antimicrobials were studied: ampicillin, amoxicillin-clavulanate, cephalosporins,
      fluoroquinolones, trimethoprim, trimethoprim-sulfamethoxazole, pivmecillinam, and
      nitrofurantoin. We applied a protocol used in earlier studies in which the level
      of antimicrobial consumption over 1 year was compared with the level of
      resistance in the next year. Statistically significant associations were found
      for nitrofurantoin use versus nitrofurantoin resistance (P < 0.0001),
      cephalosporin use versus nitrofurantoin resistance (P = 0.0293), amoxicillin use
      versus fluoroquinolone resistance (P = 0.0031), and fluoroquinolone use versus
      ampicillin resistance (P = 0.0046). Interestingly, we found only a few
      associations between resistance and antimicrobial consumption. The majority of
      the associations studied were not significant, including the association between
      fluoroquinolone use and fluoroquinolone resistance.

PMID- 19104013
TI  - Debio 025, a cyclophilin binding molecule, is highly efficient in clearing
      hepatitis C virus (HCV) replicon-containing cells when used alone or in
      combination with specifically targeted antiviral therapy for HCV (STAT-C)
      inhibitors.
AB  - Debio 025 is a potent inhibitor of hepatitis C virus (HCV) replication (J.
      Paeshuyse et al., Hepatology 43:761-770, 2006). In phase I clinical studies,
      monotherapy (a Debio 025 dose of 1,200 mg twice a day) resulted in a mean maximal
      decrease in the viral load of 3.6 log(10) units (R. Flisiak et al., Hepatology
      47:817-826, 2008), whereas a reduction of 4.6 log(10) units was obtained in phase
      II studies when Debio 025 was combined with interferon (R. Flisiak et al., J.
      Hepatol., 48:S62, 2008). We here report on the particular characteristics of the
      in vitro anti-HCV activities of Debio 025. The combination of Debio 025 with
      either ribavirin or specifically targeted antiviral therapy for HCV (STAT-C)
      inhibitors (NS3 protease or NS5B [nucleoside and nonnucleoside] polymerase
      inhibitors) resulted in additive antiviral activity in short-term antiviral
      assays. Debio 025 has the unique ability to clear hepatoma cells from their HCV
      replicon when it is used alone or in combination with interferon and STAT-C
      inhibitors. Debio 025, when it was used at concentrations that have been observed
      in human plasma (0.1 or 0.5 muM), was able to delay or prevent the development of
      resistance to HCV protease inhibitors as well as to nucleoside and nonnucleoside
      polymerase inhibitors. Debio 025 forms an attractive drug candidate for the
      treatment of HCV infections in combination with standard interferon-based
      treatment and treatments that directly target the HCV polymerase and/or protease.

PMID- 19104014
TI  - Multiple peptides homologous to herpes simplex virus type 1 glycoprotein B
      inhibit viral infection.
AB  - The 773-residue ectodomain of the herpes simplex virus type 1 (HSV-1)
      glycoprotein B (gB) has been resistant to the use of mutagenic strategies because
      the majority of the induced mutations result in defective proteins. As an
      alternative strategy for the identification of functionally important regions and
      novel inhibitors of infection, we prepared a library of overlapping peptides
      homologous to the ectodomain of gB and screened for the ability of the peptides
      to block infection. Seven of 138 15-mer peptides inhibited infection by more than
      50% at a concentration of 100 microM. Three peptides (gB94, gB122, and gB131)
      with 50% effective concentrations (EC(50)s) below 20 microM were selected for
      further studies. The gB131 peptide (residues 681 to 695 in HSV-1 gB [gB-1]) was a
      specific entry inhibitor (EC(50), approximately 12 microM). The gB122 peptide
      (residues 636 to 650 in gB-1) blocked viral entry (EC(50), approximately 18
      microM), protected cells from infection (EC(50), approximately 72 microM), and
      inactivated virions in solution (EC(50), approximately 138 microM). We were
      unable to discern the step or steps inhibited by the gB94 peptide, which is
      homologous to residues 496 to 510 in gB-1. Substitution of a tyrosine in the
      gB122 peptide (Y640 in full-length gB-1) reduced the antiviral activity
      eightfold, suggesting that this residue is critical for inhibition. This peptide
      based strategy could lead to the identification of functionally important regions
      of gB or other membrane proteins and identify novel inhibitors of HSV-1 entry.

PMID- 19104015
TI  - New composite genetic element of the Tn916 family with dual macrolide resistance
      genes in a Streptococcus pneumoniae isolate belonging to clonal complex 271.

PMID- 19104016
TI  - Population pharmacokinetics of emtricitabine in human immunodeficiency virus type
      1-infected pregnant women and their neonates.
AB  - The objectives of this study were to evaluate emtricitabine (FTC)
      pharmacokinetics in pregnant women and their neonates and to determine the
      optimal prophylactic dose for neonates after birth to prevent mother-to-child
      transmission of human immunodeficiency virus (HIV). A total of 38 HIV-infected
      pregnant women were administered tenofovir disoproxyl fumarate (300 mg)-FTC (200
      mg) tablets-two tablets at the initiation of labor and one daily for 7 days
      postpartum. By pair, 11 maternal, one cord blood, and two neonatal FTC
      concentrations were measured using a high-performance liquid chromatography
      tandem mass spectrometry validated method and analyzed by a population approach.
      Model and mean estimates (interpatient variability) were a two-compartment model
      for mothers, with an absorption rate constant of 0.54 h(-1) (61%), apparent
      elimination and intercompartmental clearances of 23.2 (17%) and 6.04 liters x h(
      1), and apparent central and peripheral volumes of 127 and 237 liters,
      respectively; an effect compartment linked to maternal circulation for cord blood
      and a neonatal compartment disconnected, after delivery, with a 10.6-h half-life
      (30%). After the 400-mg FTC administration, the median population area under the
      concentration-time curve and the minimal and maximal plasma FTC concentrations in
      pregnant women were 14.3 mg x liter(-1) x h and 1.68 and 0.076 mg/liter,
      respectively. At delivery, median (range) predicted maternal and cord blood FTC
      concentrations were, respectively, 1.16 (0.14 to 1.99) and 0.72 (0.05 to 1.19) mg
      x liter(-1). We concluded that the 400-mg FTC administration in pregnant women
      produces higher exposition than does the 200-mg administration in other adults,
      at steady state. FTC was shown to have good placental transfer (80%).
      Administering 1 mg FTC/kg as soon as possible after birth or 2 mg/kg 12 h after
      birth should produce neonatal concentrations comparable to the concentrations
      observed in adults.

PMID- 19104017
TI  - Multiple regulatory pathways associated with high-level ciprofloxacin and
      multidrug resistance in Salmonella enterica serovar enteritidis: involvement of
      RamA and other global regulators.
AB  - Mechanisms of antibiotic resistance were examined in nalidixic acid-resistant
      Salmonella enterica serovar Enteritidis field isolates displaying decreased
      susceptibility to ciprofloxacin and in in vitro-derived ciprofloxacin-resistant
      mutants (104-cip and 5408-cip). All field isolates harbored a single gyrA
      mutation (D87Y). Deletion of acrB and complementation with wild-type gyrA
      increased quinolone susceptibility. Selection for ciprofloxacin resistance was
      associated with the development of an additional gyrA (S83F) mutation in 104-cip,
      novel gyrB (E466D) and parE (V461G) mutations in 5408-cip, overexpression of acrB
      and decreased susceptibility to nonquinolone antibiotics in both mutants, and
      decreased OmpF production and altered lipopolysaccharide in 104-cip.
      Complementation of mutated gyrA and gyrB with wild-type alleles restored
      susceptibility to quinolones in 104-cip and significantly decreased the
      ciprofloxacin MIC in 5408-cip. Complementation of parE had no effect on quinolone
      MICs. Deletion of acrB restored susceptibility to ciprofloxacin and other
      antibiotics tested. Both soxS and marA were overexpressed in 104-cip, and ramA
      was overexpressed in 5408-cip. Inactivation of each of these global regulators
      lowered ciprofloxacin MICs, decreased expression of acrB, and restored
      susceptibility to other antibiotics. Mutations were found in soxR (R20H) and in
      soxS (E52K) in 104-cip and in ramR (G25A) in 5408-cip. In conclusion, both efflux
      activity and a single gyrA mutation contribute to nalidixic acid resistance and
      reduced ciprofloxacin sensitivity. Ciprofloxacin resistance and decreased
      susceptibility to multiple antibiotics can result from different genetic events
      leading to development of target gene mutations, increased efflux activity
      resulting from differential expression of global regulators associated with
      mutations in their regulatory genes, and possible altered membrane permeability.

PMID- 19104018
TI  - Mutations at embB codon 306 are an important molecular indicator of ethambutol
      resistance in Mycobacterium tuberculosis.
AB  - Ethambutol resistance in clinical Mycobacterium tuberculosis isolates is
      associated primarily with missense mutations in the embB gene. However, recent
      reports have described the presence of embB mutations, especially those at embB
      codon 306, in isolates susceptible to ethambutol. To clarify the role of embB
      mutations in ethambutol resistance, we sequenced the ethambutol resistance
      determining region in spontaneous ethambutol-resistant mutants. In our study, 66%
      of spontaneous mutants contained a single point mutation in embB, with 55% of
      these occurring at embB 306. The MIC of ethambutol for spontaneous mutants was
      increased two- to eightfold relative to the pansusceptible M. tuberculosis
      strains from which the mutants were generated. To further characterize the role
      of embB 306 mutations, we directly introduced mutant alleles, embB(M306V) or
      embB(M306I), into pansusceptible M. tuberculosis strains and conversely reverted
      mutant alleles in spontaneous ethambutol-resistant mutants back to those of the
      wild type via allelic exchange using specialized linkage transduction. We
      determined that the MIC of ethambutol was reduced fourfold for three of the four
      spontaneous ethambutol-resistant embB 306 mutants when the mutant allele was
      replaced with the wild-type embB allele. The MIC for one of the spontaneous
      mutants genetically reverted to wild-type embB was reduced by only twofold. When
      the wild-type embB allele was converted to the mutant allele embB(M306V), the
      ethambutol MIC was increased fourfold, and when the allele was changed to M306I,
      the ethambutol MIC increased twofold. Our data indicate that embB 306 mutations
      are sufficient to confer ethambutol resistance, and detection of these mutations
      should be considered in the development of rapid molecular tests.

PMID- 19104019
TI  - A novel insertion mutation in Streptomyces coelicolor ribosomal S12 protein
      results in paromomycin resistance and antibiotic overproduction.
AB  - We identified a novel paromomycin resistance-associated mutation in rpsL, caused
      by the insertion of a glycine residue at position 92, in Streptomyces coelicolor
      ribosomal protein S12. This insertion mutation (GI92) resulted in a 20-fold
      increase in the paromomycin resistance level. In combination with another S12
      mutation, K88E, the GI92 mutation markedly enhanced the production of the blue
      colored polyketide antibiotic actinorhodin and the red-colored antibiotic
      undecylprodigiosin. The gene replacement experiments demonstrated that the K88E
      GI92 double mutation in the rpsL gene was responsible for the marked enhancement
      of antibiotic production observed. Ribosomes with the K88E-GI92 double mutation
      were characterized by error restrictiveness (i.e., hyperaccuracy). Using a cell
      free translation system, we found that mutant ribosomes harboring the K88E-GI92
      double mutation but not ribosomes harboring the GI92 mutation alone displayed
      sixfold greater translation activity relative to that of the wild-type ribosomes
      at late growth phase. This resulted in the overproduction of actinorhodin, caused
      by the transcriptional activation of the pathway-specific regulatory gene actII
      orf4, possibly due to the increased translation of transcripts encoding
      activators of actII-orf4. The mutant with the K88E-GI92 double mutation
      accumulated a high level of ribosome recycling factor at late stationary phase,
      underlying the high level of protein synthesis activity observed.

PMID- 19104020
TI  - Immobilization reduces the activity of surface-bound cationic antimicrobial
      peptides with no influence upon the activity spectrum.
AB  - Early studies of immobilized peptides mainly focused upon the relationship
      between structural properties and the activity of soluble and surface-tethered
      sequences. The intention of this study was to analyze the influence of
      immobilization parameters upon the activity profile of peptides. Resin beads
      (TentaGel S NH(2), HypoGel 400 NH(2), and HypoGel 200 NH(2)) with polyethylene
      glycol spacers of different lengths were rendered antimicrobial by linkage of an
      amphipathic model KLAL peptide and magainin-derived MK5E. Standard solid-phase
      peptide synthesis, thioalkylation, and ligation strategies were used to
      immobilize the peptides at the C and N termini and via different side-chain
      positions. Depending upon the resin capacity and the coupling strategies, peptide
      loading ranged between 0.1 and 0.25 micromol/mg for C-terminally and around 0.03
      micromol/mg for N-terminally and side-chain-immobilized peptides. Tethering
      conserved the activity spectra of the soluble peptides at reduced concentrations.
      The resin-bound peptides were antimicrobial toward Escherichia coli and Bacillus
      subtilis in the millimolar range compared to the results seen with micromolar
      concentrations of the free peptides. B. subtilis was more susceptible than E.
      coli. The antimicrobial activity distinctly decreased with reduction of the
      spacer length. Slight differences in the antimicrobial effect of KLAL and MK5E
      bound at different chain positions on TentaGel S NH(2) suggest that the activity
      is less dependent upon the position of immobilization. Soluble KLAL was active
      toward red blood cells, whereas MK5E was nonhemolytic at up to about 400 microM.
      Resin-induced hemolysis hampered the determination of the hemolytic effect of the
      immobilized peptides. TentaGel S NH(2)-bound peptides enhanced the permeability
      of the POPC (1-palmitoyl-2-oleoyl-sn-glycero-3-phospho-choline) and mixed POPC/1
      palmitoyl-2-oleoyl-sn-glycero-3-[phospho-rac-(1-glycerol)] (POPC/POPG) bilayers
      used to model the charge properties of the biological targets. The results
      suggest that surface immobilization of the cationic amphipathic antimicrobial
      peptides does not influence the membrane-permeabilizing mode of action. Peptide
      insertion into the target membrane and likely the exchange of membrane
      stabilizing bivalent cations contribute to the antimicrobial effect. In
      conclusion, reasonable antimicrobial activity of surface-bound peptides requires
      the optimization of the coupling parameters, with the length of the spacer and
      the amount of target-accessible peptide being the most important factors.

PMID- 19104021
TI  - CMY-31 and CMY-36 cephalosporinases encoded by ColE1-like plasmids.
AB  - Two CMY-2 derivatives, CMY-31 (Gln(215)-->Arg) from Salmonella enterica serotype
      Newport and CMY-36 (Ala(77)-->Cys and Gln(193)-->Glu) from Klebsiella pneumoniae,
      were characterized. Both cephalosporinases functionally resembled CMY-2. bla(CMY)
      alleles occurred as parts of a putative transposon comprising ISEcp1B and a
      Citrobacter freundii-derived sequence carried by ColE1-like plasmids similar to
      CMY-5-encoding pTKH11 from Klebsiella oxytoca.

PMID- 19104022
TI  - Antibiotic resistance in urinary isolates of Escherichia coli from college women
      with urinary tract infections.
AB  - Of 176 urine isolates from female students positive for Escherichia coli, 29.6%
      were trimethoprim-sulfamethoxazole resistant and none were nitrofurantoin
      resistant. Among students with a history of urinary tract infection (UTI) (n =
      119), resistance to ciprofloxacin was 11.8%, compared to 1.8% among those without
      prior UTI. Nitrofurantoin should be considered for empirical therapy of lower
      tract UTI.

PMID- 19104024
TI  - Breakthrough Aspergillus fumigatus and Candida albicans double infection during
      caspofungin treatment: laboratory characteristics and implication for
      susceptibility testing.
AB  - Caspofungin is used for the treatment of acute invasive candidiasis and as
      salvage treatment for invasive aspergillosis. We report characteristics of
      isolates of Candida albicans and Aspergillus fumigatus detected in a patient with
      breakthrough infection complicating severe gastrointestinal surgery and evaluate
      the capability of susceptibility methods to identify candin resistance. The
      susceptibility of C. albicans to caspofungin and anidulafungin was investigated
      by Etest, microdilution (European Committee on Antibiotic Susceptibility Testing
      [EUCAST] and CLSI), disk diffusion, agar dilution, and FKS1 sequencing and in a
      mouse model. Tissue was examined by immunohistochemistry, PCR, and sequencing for
      the presence of A. fumigatus and resistance mutations. The MICs for the C.
      albicans isolate were as follows: >32 microg/ml caspofungin and 0.5 microg/ml
      anidulafungin by Etest, 2 microg/ml caspofungin and 0.125 microg/ml anidulafungin
      by EUCAST methods, and 1 microg/ml caspofungin and 0.5 microg/ml anidulafungin by
      CLSI methods. Sequencing of the FKS1 gene revealed a mutation leading to an S645P
      substitution. Caspofungin and anidulafungin failed to reduce kidney CFU counts in
      animals inoculated with this isolate (P > 0.05 compared to untreated control
      animals), while both candins completely sterilized the kidneys in animals
      infected with a control isolate. Disk diffusion and agar dilution methods clearly
      separated the two isolates. Immunohistochemistry and sequencing confirmed the
      presence of A. fumigatus without FSK1 resistance mutations in liver and lung
      tissues. Breakthrough disseminated aspergillosis and candidiasis developed
      despite an absence of characteristic FKS1 resistance mutations in the Aspergillus
      isolates. EUCAST and CLSI methodology did not separate the candin-resistant
      clinical isolate from the sensitive control isolate as well as did the Etest and
      agar methods.

PMID- 19104023
TI  - In vivo and in vitro efficacy of amodiaquine monotherapy for treatment of
      infection by chloroquine-resistant Plasmodium vivax.
AB  - Amodiaquine retains efficacy against infection by chloroquine-resistant
      Plasmodium falciparum; however, little information is available on its efficacy
      against infection by chloroquine-resistant Plasmodium vivax. Patients presenting
      to a rural clinic with a pure P. vivax infection that recurred after recent
      antimalarial treatment were retreated, this time with amodiaquine monotherapy,
      and the risk of further recurrence within 4 weeks was assessed. Of the 87
      patients with pure P. vivax infection, 15 patients did not complete a full course
      of treatment, 4 of whom were intolerant to treatment. In the 72 patients
      completing treatment, 91% (63 of 69) had cleared their parasitemia within 48 h
      with no early treatment failure. Follow-up to day 28 or recurrent parasitemia was
      achieved for 56 patients (78%). The cumulative incidence of treatment failure by
      day 28 was 22.8% (95% confidence interval, 7.3 to 38%). The in vitro sensitivity
      profile was determined for a separate set of isolates from outpatients with pure
      P. vivax infection. The median 50% inhibitory concentration of amodiaquine was
      11.3 nM (range, 0.37 to 95.8) and was correlated significantly with that of
      chloroquine (Spearman rank correlation coefficient, 0.602; P < 0.001). Although
      amodiaquine results in a rapid clinical response, the risk of recurrence by day
      28 is unacceptably high, reducing its suitability as an alternative treatment of
      infection by chloroquine-resistant P. vivax in this region.

PMID- 19104025
TI  - Affinity of Tomopenem (CS-023) for penicillin-binding proteins in Staphylococcus
      aureus, Escherichia coli, and Pseudomonas aeruginosa.
AB  - Tomopenem (formerly CS-023), a novel 1beta-methylcarbapenem, exhibited high
      affinity for penicillin-binding protein (PBP) 2 in Staphylococcus aureus, PBP 2
      in Escherichia coli, and PBPs 2 and 3 in Pseudomonas aeruginosa, which are
      considered major lethal targets. Morphologically, tomopenem induced spherical
      forms in E. coli and short filamentation with bulges in P. aeruginosa, which
      correlated with the drug's PBP profiles. The potential of resistance of these
      bacteria to tomopenem was comparable to that to imipenem.

PMID- 19104026
TI  - Changes in aac(6')-Ib-cr prevalence and fluoroquinolone resistance in nosocomial
      isolates of Escherichia coli collected from 1991 through 2005.
AB  - Clinical isolates of Escherichia coli collected from 1991 through 2005 at a
      tertiary-care center were studied for qnr and aac(6')-Ib-cr genes. Isolates
      bearing aac(6')-Ib-cr emerged in 1998, coinciding with an increase in
      ciprofloxacin resistance. The presence of aac(6')-Ib-cr was multiclonal and was
      associated with the presence of extended-spectrum beta-lactamases.

PMID- 19104027
TI  - Oritavancin kills stationary-phase and biofilm Staphylococcus aureus cells in
      vitro.
AB  - Slow-growing bacteria and biofilms are notoriously tolerant to antibiotics.
      Oritavancin is a lipoglycopeptide with multiple mechanisms of action that
      contribute to its bactericidal action against exponentially growing gram-positive
      pathogens, including the inhibition of cell wall synthesis and perturbation of
      membrane barrier function. We sought to determine whether oritavancin could
      eradicate cells known to be tolerant to many antimicrobial agents, that is,
      stationary-phase and biofilm cultures of Staphylococcus aureus in vitro.
      Oritavancin exhibited concentration-dependent bactericidal activity against
      stationary-phase inocula of methicillin-susceptible S. aureus (MSSA) ATCC 29213,
      methicillin-resistant S. aureus (MRSA) ATCC 33591, and vancomycin-resistant S.
      aureus (VRSA) VRS5 inoculated into nutrient-depleted cation-adjusted Mueller
      Hinton broth. As has been described for exponential-phase cells, oritavancin
      induced membrane depolarization, increased membrane permeability, and caused
      ultrastructural defects including a loss of nascent septal cross walls in
      stationary-phase MSSA. Furthermore, oritavancin sterilized biofilms of MSSA,
      MRSA, and VRSA at minimal biofilm eradication concentrations (MBECs) of between
      0.5 and 8 mug/ml. Importantly, MBECs for oritavancin were within 1 doubling
      dilution of their respective planktonic broth MICs, highlighting the potency of
      oritavancin against biofilms. These results demonstrate a significant activity of
      oritavancin against S. aureus in phases of growth that exhibit tolerance to other
      antimicrobial agents.

PMID- 19104028
TI  - Pharmacokinetics of high-dose oseltamivir in healthy volunteers.
AB  - The effects of loading doses and probenecid coadministration on oseltamivir
      pharmacokinetics at four increasing dose levels in groups of eight healthy adult
      Thai volunteers (125 individual series) were evaluated. Doses of up to 675 mg
      were well-tolerated. The pharmacokinetics were dose linear. Oseltamivir phosphate
      (OS) was rapidly and completely absorbed and converted (median conversion level,
      93%) to the active carboxylate metabolite. Median elimination half-lives (and 95%
      confidence intervals [CI]) were 1.0 h (0.9 to 1.1 h) for OS and 5.1 h (4.7 to 5.7
      h) for oseltamivir carboxylate (OC). One subject repeatedly showed markedly
      reduced OS-to-OC conversion, indicating constitutionally impaired
      carboxylesterase activity. The coadministration of probenecid resulted in a mean
      contraction in the apparent volume of distribution of OC of 40% (95% CI, 37 to
      44%) and a reduction in the renal elimination of OC of 61% (95% CI, 58 to 62%),
      thereby increasing the median area under the concentration-time curve (AUC) for
      OC by 154% (range, 71 to 278%). The AUC increase for OC in saliva was
      approximately three times less than the AUC increase for OC in plasma. A loading
      dose 1.25 times the maintenance dose should be given for severe influenza
      pneumonia. Probenecid coadministration may allow considerable dose saving for
      oseltamivir, but more information on OC penetration into respiratory secretions
      is needed to devise appropriate dose regimens.

PMID- 19104029
TI  - Antifungal therapy of Aspergillus invasive otitis externa: efficacy of
      voriconazole and review.
AB  - Invasive otitis externa (IOE) due to Aspergillus is a rare, potentially life
      threatening, invasive fungal infection affecting immunocompromised patients. The
      invasive process may lead to skull base osteomyelitis with progressive cranial
      nerve palsies and can result in irreversible hearing and neurological impairment.
      We report two cases of Aspergillus IOE treated with voriconazole alone and a
      literature review of antifungal therapy of Aspergillus IOE. Twenty-five patients,
      including the two described in the present report, were analyzed. Eighteen
      patients were treated with amphotericin B, and nine of them received itraconazole
      as an additional agent. Three patients received initial therapy with
      itraconazole, and one patient was treated with both voriconazole and caspofungin
      therapy. The two patients in the present report received voriconazole therapy
      alone with good clinical and biological tolerance despite prolonged treatment.
      The last patient did not receive antifungal therapy, as the diagnosis was made
      postmortem. Eighteen patients underwent an initial extensive surgical
      debridement. The majority of the patients had a favorable outcome, 17 patients
      experienced a complete recovery, and 6 showed a partial improvement. Both of the
      patients reported on here had favorable outcomes, and no aggressive surgical
      debridement was required. Although voriconazole has been shown to be effective
      for the treatment of invasive aspergillosis, its precise role in the management
      of Aspergillus IOE had not been documented. These observations demonstrate that
      voriconazole could be an effective and well-tolerated therapeutic option for the
      management of Aspergillus IOE.

PMID- 19104031
TI  - The Anxiety Sensitivity Index--Revised: confirmatory factor analyses, structural
      invariance in Caucasian and African American samples, and score reliability and
      validity.
AB  - The most commonly used measure of anxiety sensitivity is the 36-item Anxiety
      Sensitivity Index-Revised (ASI-R). Exploratory factor analyses have produced
      several different factors structures for the ASI-R, but an acceptable fit using
      confirmatory factor analytic approaches has only been found for a 21-item version
      of the instrument. We evaluated the fit of all published factor models for the 36
      and 21-item ASI-R, modified the hierarchical model using an approach that does
      not eliminate items, evaluated the invariance of the modified model across
      Caucasian and African-American subsamples, and compared the reliability and
      validity of the 36-item and 21-item versions. The 21-item version of the ASI-R
      fit a four factor model, as did the 36-item version after several meaningful
      model modifications. The modified 36-item model was replicable in independent
      cases and its structural properties were generally invariant across race. Scores
      from the 36-item version exhibited superior reliability and criterion-related
      validity.

PMID- 19104030
TI  - Discriminative stimulus and subject-rated effects of methamphetamine, d
      amphetamine, methylphenidate, and triazolam in methamphetamine-trained humans.
AB  - Methamphetamine abuse is a significant public health concern. Although widely
      studied in laboratory animals, little is known about the abuse-related behavioral
      effects of methamphetamine relative to other abused stimulants in controlled
      laboratory settings in humans. The aim of this study was to examine the
      discriminative stimulus, subject-rated, performance, and cardiovascular effects
      of methamphetamine in humans. In the present study, subjects first learned to
      discriminate 10 mg of oral methamphetamine from placebo. After acquiring the
      discrimination (> or = 80% drug-appropriate responding on four consecutive
      sessions), a range of oral doses of methamphetamine (2.5-15 mg), d-amphetamine
      (2.5-15 mg), methylphenidate (5-30 mg), and triazolam (0.0625-0.375 mg) was
      tested. Methamphetamine functioned as a discriminative stimulus and produced
      prototypical stimulant-like subject-rated effects. d-Amphetamine and
      methylphenidate produced dose-related increases in methamphetamine-appropriate
      responding, whereas triazolam did not. d-Amphetamine and methylphenidate produced
      stimulant-like behavioral effects, whereas triazolam produced sedative-like
      effects. Methamphetamine, but no other drug, increased heart rate, systolic
      pressure, and diastolic pressure significantly above placebo levels. Performance
      in the Digit-Symbol Substitution Test was not affected by any of the drugs
      tested. Overall, these results demonstrate that the acute behavioral effects of
      methamphetamine, d-amphetamine, and methylphenidate overlap extensively in
      humans, which is concordant with findings from preclinical studies. Future
      studies should assess whether the similarity in the behavioral effects of
      methamphetamine and related stimulants can be extended to other behavioral
      assays, such as measures of reinforcement, in humans.

PMID- 19104032
TI  - Autologous chondrocyte implantation of the ankle: a 2- to 5-year follow-up.
AB  - BACKGROUND: Treatment of full-thickness talar cartilage defects that have failed
      previous surgery is problematic without a definitive solution. PURPOSE: To report
      the first US prospective study of autologous chondrocyte implantation of the
      talus. STUDY DESIGN: Case series; Level of evidence, 4. METHODS: Eleven patients
      (6 women and 5 men; mean age, 33 years) underwent autologous chondrocyte
      implantation of the talus after previous failed surgical management. There were 9
      medial and 2 lateral lesions, with a mean size of 21 x 13 mm (273 mm2). Five
      patients underwent autologous chondrocyte implantation of the talus alone; 6 had
      it with a "sandwich procedure." Ten patients underwent a second-look arthroscopy
      with screw removal. RESULTS: Mean follow-up was 38 months. Preoperatively, 10
      patients rated their ankles as poor and 1 as fair, using the simplified
      symptomatology evaluation. At latest follow-up, 3 patients were classified as
      excellent, 6 as good, and 2 as fair. Tegner activity level improved from 1.3 +/-
      1.0 (mean +/- SE) preoperatively to 4.0 +/- 1.6 (P < .002) postoperatively. The
      Finsen score (modified Weber score) showed significant improvement in the total
      score (P < .001). There was also overall agreement between the Finsen score and
      the American Orthopaedic Foot and Ankle Society ankle hindfoot score, with
      significant improvement from 47.4 +/- 17.4 preoperatively to 84.3 +/- 8.1
      postoperatively (P < .001). At repeat arthroscopy, complete coverage of the
      defect was seen in all patients. CONCLUSION: Autologous chondrocyte implantation
      of the talus yields significant functional improvement; however, further
      investigation is necessary to determine the long-term structural and
      biomechanical properties of the repair tissue.

PMID- 19104033
TI  - Trends in disability-free life expectancy among Chinese older adults.
AB  - OBJECTIVE: This study evaluates trends in disability-free life expectancy (DFLE)
      of Chinese adults aged 60 and older. METHODS: Based on two national disability
      surveys in 1987 and 2006 as well as mortality data from World Population
      Prospects, the Sullivan method was used to calculate DFLE. RESULTS: DFLE
      increased from 13.0 to 13.9 years at age 60 and from 1.2 to 1.5 years at age 90
      in 1987 and 2006, respectively. The proportion of DFLE increased after age 75.
      The proportion of DLE(x) with severe disability decreased while that of least
      disability increased. Onset of disability was delayed from 0.3 years to 4.7 years
      across disability types. CONCLUSIONS: Trends in DFLE by age and severity of
      disability as well as the delayed onset of disability provide evidence for the
      compression of morbidity among the oldest old in China. But a similar trend was
      not found among the young-old.

PMID- 19104034
TI  - Increased mortality risk in older adults with persistently low or declining
      feelings of usefulness to others.
AB  - OBJECTIVE: This study seeks to determine if persistently low or declining
      feelings of usefulness to others in later life predict increased mortality hazard
      in older adults. METHOD: Data on change in perceptions of usefulness, health,
      behavioral and psychosocial covariates, and mortality originate from the
      MacArthur Study of Successful Aging, a prospective study of 1,189 older adults
      (aged 70 to 79). RESULTS: Older adults with persistently low feelings of
      usefulness or who experienced a decline to low feelings of usefulness during the
      first 3 years of the study experienced a greater hazard of mortality
      (sociodemographic adjusted hazard ratio = 1.75; 95% confidence interval = 1.22,
      2.51) during a subsequent 9-year follow-up as compared to older adults with
      persistently high feelings of usefulness. DISCUSSION: Older adults with
      persistently low perceived usefulness or feelings of usefulness that decline to a
      low level may be a vulnerable group with increased risk for poor health outcomes
      in later life.

PMID- 19104035
TI  - Explosively launched spores of ascomycete fungi have drag-minimizing shapes.
AB  - The forcibly launched spores of ascomycete fungi must eject through several
      millimeters of nearly still air surrounding fruiting bodies to reach dispersive
      air flows. Because of their microscopic size, spores experience great fluid drag,
      and although this drag can aid transport by slowing sedimentation out of
      dispersive air flows, it also causes spores to decelerate rapidly after launch.
      We hypothesize that spores are shaped to maximize their range in the nearly still
      air surrounding fruiting bodies. To test this hypothesis we numerically calculate
      optimal spore shapes-shapes of minimum drag for prescribed volumes-and compare
      these shapes with real spore shapes taken from a phylogeny of >100 species. Our
      analysis shows that spores are constrained to remain within 1% of the minimum
      possible drag for their size. From the spore shapes we predict the speed of spore
      launch, and confirm this prediction through high-speed imaging of ejection in
      Neurospora tetrasperma. By reconstructing the evolutionary history of spore
      shapes within a single ascomycete family we measure the relative contributions of
      drag minimization and other shape determinants to spore shape evolution. Our
      study uses biomechanical optimization as an organizing principle for explaining
      shape in a mega-diverse group of species and provides a framework for future
      measurements of the forces of selection toward physical optima.

PMID- 19104037
TI  - Prediction of incommensurate crystal structure in Ca at high pressure.
AB  - Ca shows an interesting high-pressure phase transformation sequence, but, despite
      similar physical properties at high pressure and affinity in the electronic
      structure with its neighbors in the periodic table, no complex phase has been
      identified for Ca so far. We predict an incommensurate high-pressure phase of Ca
      from first principle calculations and describe a procedure of estimating
      incommensurate structure parameters by means of electronic structure calculations
      for periodic crystals. Thus, by using the ab initio technique for periodic
      structures, one can get not only reliable information about the electronic
      structure and structural parameters of an incommensurate phase, but also identify
      and predict such phases in new elements.

PMID- 19104036
TI  - Differential trafficking of AMPA and NMDA receptors by SAP102 and PSD-95
      underlies synapse development.
AB  - The development of glutamatergic synapses involves changes in the number and type
      of receptors present at the postsynaptic density. To elucidate molecular
      mechanisms underlying these changes, we combine in utero electroporation of
      constructs that alter the molecular composition of developing synapses with dual
      whole-cell electrophysiology to examine synaptic transmission during two distinct
      developmental stages. We find that SAP102 mediates synaptic trafficking of AMPA
      and NMDA receptors during synaptogenesis. Surprisingly, after synaptogenesis, PSD
      95 assumes the functions of SAP102 and is necessary for two aspects of synapse
      maturation: the developmental increase in AMPA receptor transmission and
      replacement of NR2B-NMDARs with NR2A-NMDARs. In PSD-95/PSD-93 double-KO mice, the
      maturational replacement of NR2B- with NR2A-NMDARs fails to occur, and PSD-95
      expression fully rescues this deficit. This study demonstrates that SAP102 and
      PSD-95 regulate the synaptic trafficking of distinct glutamate receptor subtypes
      at different developmental stages, thereby playing necessary roles in excitatory
      synapse development.

PMID- 19104039
TI  - Compensatory IKKalpha activation of classical NF-kappaB signaling during IKKbeta
      inhibition identified by an RNA interference sensitization screen.
AB  - A subtype of diffuse large B-cell lymphoma (DLBCL), termed activated B-cell-like
      (ABC) DLBCL, depends on constitutive nuclear factor-kappaB (NF-kappaB) signaling
      for survival. Small molecule inhibitors of IkappaB kinase beta (IKKbeta), a key
      regulator of the NF-kappaB pathway, kill ABC DLBCL cells and hold promise for the
      treatment of this lymphoma type. We conducted an RNA interference genetic screen
      to investigate potential mechanisms of resistance of ABC DLBCL cells to IKKbeta
      inhibitors. We screened a library of small hairpin RNAs (shRNAs) targeting 500
      protein kinases for shRNAs that would increase the killing of an ABC DLBCL cell
      line in the presence of a small molecule IKKbeta inhibitor. Two independent
      shRNAs targeting IKKalpha synergized with the IKKbeta inhibitor to kill three
      different ABC DLBCL cell lines but were not toxic by themselves. Surprisingly,
      IKKalpha shRNAs blocked the classical rather than the alternative NF-kappaB
      pathway in ABC DLBCL cells, as judged by inhibition of IkappaBalpha
      phosphorylation. IKKalpha shRNA toxicity was reversed by coexpression of wild
      type but not kinase inactive forms of IKKalpha, suggesting that IKKalpha may
      directly phosphorylate IkappaBalpha under conditions of IKKbeta inhibition. In
      models of physiologic NF-kappaB pathway activation by CARD11 or tumor necrosis
      factor-alpha, compensatory IKKalpha activity was also observed with IKKbeta
      inhibition. These results suggest that therapy for ABC DLBCL may be improved by
      targeting both IKKalpha and IKKbeta, possibly through CARD11 inhibition.

PMID- 19104038
TI  - MIG-17/ADAMTS controls cell migration by recruiting nidogen to the basement
      membrane in C. elegans.
AB  - Mutations in the a disintegrin and metalloprotease with thrombospondin motifs
      (ADAMTS) family of secreted proteases cause diseases linked to ECM abnormalities.
      However, the mechanisms by which these enzymes modulate the ECM during
      development are mostly unexplored. The Caenorhabditis elegans MIG-17/ADAMTS
      protein is secreted from body wall muscle cells and localizes to the basement
      membrane (BM) of the developing gonad where it controls directional migration of
      gonadal leader cells. Here we show that specific amino acid changes in the ECM
      proteins fibulin-1C (FBL-1C) and type IV collagen (LET-2) result in bypass of the
      requirement for MIG-17 activity in gonadal leader cell migration in a nidogen
      (NID-1)-dependent and -independent manner, respectively. The MIG-17, FBL-1C and
      LET-2 activities are required for proper accumulation of NID-1 at the gonadal BM.
      However, mutant FBL-1C or LET-2 in the absence of MIG-17 promotes NID-1
      localization. Furthermore, overexpression of NID-1 in mig-17 mutants
      substantially rescues leader cell migration defects. These results suggest that
      functional interactions among BM molecules are important for MIG-17 control of
      gonadal leader cell migration. We propose that FBL-1C and LET-2 act downstream of
      MIG-17-dependent proteolysis to recruit NID-1 and that LET-2 also activates a NID
      1-independent pathway, thereby inducing the remodeling of the BM required for
      directional control of leader cell migration.

PMID- 19104040
TI  - How the Dorsal gradient works: insights from postgenome technologies.
AB  - Gradients of extracellular signaling molecules and transcription factors are used
      in a variety of developmental processes, including the patterning of the
      Drosophila embryo, the establishment of diverse neuronal cell types in the
      vertebrate neural tube, and the anterior-posterior patterning of vertebrate
      limbs. Here, we discuss how a gradient of the maternal transcription factor
      Dorsal produces complex patterns of gene expression across the dorsal-ventral
      (DV) axis of the early Drosophila embryo. The identification of 60-70 Dorsal
      target genes, along with the characterization of approximately 35 associated
      regulatory DNAs, suggests that there are at least six different regulatory codes
      driving diverse DV expression profiles.

PMID- 19104041
TI  - Filament rigidity causes F-actin depletion from nonbinding surfaces.
AB  - Proximity to membranes is required of actin networks for many key cell functions,
      including mechanics and motility. However, F-actin rigidity should hinder a
      filament's approach to surfaces. Using confocal microscopy, we monitor the
      distribution of fluorescent actin near nonadherent glass surfaces. Initially
      uniform, monomers polymerize to create a depletion zone where F-actin is absent
      at the surface but increases monotonically with distance from the surface. At its
      largest, depletion effects can extend >35 microm, comparable with the average,
      mass-weighted filament length. Increasing the rigidity of actin filaments with
      phalloidin increases the extent of depletion, whereas shortening filaments by
      using capping protein reduces it proportionally. In addition, depletion kinetics
      are faster with higher actin concentrations, consistent with faster
      polymerization and faster Brownian-ratchet-driven motion. Conversely, the extent
      of depletion decreases with actin concentration, suggesting that entropy is the
      thermodynamic driving force. Quantitatively, depletion kinetics and extent match
      existing actin kinetics, rigidity, and lengths. However, explaining depletion
      profiles and concentration dependence (power-law of -1) requires modifying the
      rigid rod model. Within cells, surface depletion should slow membrane-associated
      F-actin reactions another approximately 10-fold beyond hydrodynamically slowed
      diffusion of filaments (approximately 10-fold). In addition, surface depletion
      should cause membranes to bend spontaneously toward filaments. Such depletion
      principles underlie the thermodynamics of all surface-associated reactions with
      mechanical structures, ranging from DNA to filaments to networks. For various
      functions, cells must actively resist the thermodynamics of depletion.

PMID- 19104042
TI  - Culture, population structure, and low genetic diversity in Pleistocene hominins.
AB  - Paleogenomic research has shown that modern humans, Neanderthals, and their most
      recent common ancestor have displayed less genetic diversity than living great
      apes. The traditional interpretation that low levels of genetic diversity in
      modern humans resulted from a relatively recent demographic bottleneck cannot
      account for similarly low levels of genetic diversity in Middle Pleistocene
      hominins. A more parsimonious hypothesis proposes that the effective population
      size of the human lineage has been low for more than 500,000 years, but the
      mechanism responsible for suppressing genetic diversity in Pleistocene hominin
      populations without similarly affecting that of their hominoid contemporaries
      remains unknown. Here we use agent-based simulation to study the effect of
      culturally mediated migration on neutral genetic diversity in structured
      populations. We show that, in populations structured by culturally mediated
      migration, selection can suppress neutral genetic diversity over thousands of
      generations, even in the absence of bottlenecks or expansions in census
      population size. In other words, selection could have suppressed the effective
      population size of Pleistocene hominins for as long as the degree of cultural
      similarity between regionally differentiated groups played an important role in
      mediating intraspecific gene flow.

PMID- 19104043
TI  - A chemical biology approach reveals period shortening of the mammalian circadian
      clock by specific inhibition of GSK-3beta.
AB  - The circadian clock controls daily oscillations of gene expression at the
      cellular level. We report the development of a high-throughput circadian
      functional assay system that consists of luminescent reporter cells, screening
      automation, and a data analysis pipeline. We applied this system to further
      dissect the molecular mechanisms underlying the mammalian circadian clock using a
      chemical biology approach. We analyzed the effect of 1,280 pharmacologically
      active compounds with diverse structures on the circadian period length that is
      indicative of the core clock mechanism. Our screening paradigm identified many
      compounds previously known to change the circadian period or phase, demonstrating
      the validity of the assay system. Furthermore, we found that small molecule
      inhibitors of glycogen synthase kinase 3 (GSK-3) consistently caused a strong
      short period phenotype in contrast to the well-known period lengthening by
      lithium, another presumed GSK-3 inhibitor. siRNA-mediated knockdown of GSK-3beta
      also caused a short period, confirming the phenotype obtained with the small
      molecule inhibitors. These results clarify the role of GSK-3beta in the period
      regulation of the mammalian clockworks and highlight the effectiveness of
      chemical biology in exploring unidentified mechanisms of the circadian clock.

PMID- 19104044
TI  - Fossil evidence for the origin of spider spinnerets, and a proposed arachnid
      order.
AB  - Silk production from opisthosomal glands is a defining characteristic of spiders
      (Araneae). Silk emerges from spigots (modified setae) borne on spinnerets
      (modified appendages). Spigots from Attercopus fimbriunguis, from Middle Devonian
      (386 Ma) strata of Gilboa, New York, were described in 1989 as evidence for the
      oldest spider and the first use of silk by animals. Slightly younger (374 Ma)
      material from South Mountain, New York, conspecific with A. fimbriunguis,
      includes spigots and other evidence that elucidate the evolution of early Araneae
      and the origin of spider silk. No known Attercopus spigots, including the
      original specimen, occur on true spinnerets but are arranged along the edges of
      plates. Spinnerets originated from biramous appendages of opisthosomal somites 4
      and 5; although present in Limulus, no other arachnids have opisthosomal
      appendage homologues on these segments. The spigot arrangement in Attercopus
      shows a primitive state before the reexpression of the dormant genetic mechanism
      that gave rise to spinnerets in later spiders. Enigmatic flagellar structures
      originally described as Arachnida incertae sedis, are shown to be Attercopus anal
      flagella, as found in Permarachne, also originally described as a spider. An
      arachnid order, Uraraneida, is erected for a plesion, including these two genera,
      based on this combination of characters. The inability of Uraraneida precisely to
      control silk weaving suggests its original use as a wrapping, lining, or homing
      material.

PMID- 19104045
TI  - A large-scale analysis of tissue-specific pathology and gene expression of human
      disease genes and complexes.
AB  - Heritable diseases are caused by germ-line mutations that, despite tissuewide
      presence, often lead to tissue-specific pathology. Here, we make a systematic
      analysis of the link between tissue-specific gene expression and pathological
      manifestations in many human diseases and cancers. Diseases were systematically
      mapped to tissues they affect from disease-relevant literature in PubMed to
      create a disease-tissue covariation matrix of high-confidence associations of
      >1,000 diseases to 73 tissues. By retrieving >2,000 known disease genes, and
      generating 1,500 disease-associated protein complexes, we analyzed the
      differential expression of a gene or complex involved in a particular disease in
      the tissues affected by the disease, compared with nonaffected tissues. When this
      analysis is scaled to all diseases in our dataset, there is a significant
      tendency for disease genes and complexes to be overexpressed in the normal
      tissues where defects cause pathology. In contrast, cancer genes and complexes
      were not overexpressed in the tissues from which the tumors emanate. We
      specifically identified a complex involved in XY sex reversal that is testis
      specific and down-regulated in ovaries. We also identified complexes in Parkinson
      disease, cardiomyopathies, and muscular dystrophy syndromes that are similarly
      tissue specific. Our method represents a conceptual scaffold for organism
      spanning analyses and reveals an extensive list of tissue-specific draft
      molecular pathways, both known and unexpected, that might be disrupted in
      disease.

PMID- 19104046
TI  - A regulatory module embedded in the coding region of Hoxa2 controls expression in
      rhombomere 2.
AB  - Here, we define a gene regulatory network for Hoxa2, responsible for temporal and
      spatial expression in hindbrain development. Hoxa2 plays an important role in
      regulating the regional identity of rhombomere 2 (r2) and is the only Hox gene
      expressed in this segment. In this study, we found that a Hoxa2 cis-regulatory
      module consists of five elements that direct expression in r2 of the developing
      hindbrain. Surprisingly, the module is imbedded in the second coding exon of
      Hoxa2 and therefore may be constrained by both protein coding and gene regulatory
      requirements. This highly conserved enhancer consists of two consensus Sox
      binding sites and several additional elements that act in concert to direct
      strong r2 specific expression. Our findings provide important insight into the
      regulation of segmental identity in the anterior hindbrain. Furthermore, they
      have broader implications in designing arrays and interpreting data from global
      analyses of gene regulation because regulatory input from coding regions needs to
      be considered.

PMID- 19104047
TI  - The Caenorhabditis elegans vulva: a post-embryonic gene regulatory network
      controlling organogenesis.
AB  - The Caenorhabditis elegans vulva is an elegant model for dissecting a gene
      regulatory network (GRN) that directs postembryonic organogenesis. The mature
      vulva comprises seven cell types (vulA, vulB1, vulB2, vulC, vulD, vulE, and
      vulF), each with its own unique pattern of spatial and temporal gene expression.
      The mechanisms that specify these cell types in a precise spatial pattern are not
      well understood. Using reverse genetic screens, we identified novel components of
      the vulval GRN, including nhr-113 in vulA. Several transcription factors (lin-11,
      lin-29, cog-1, egl-38, and nhr-67) interact with each other and act in concert to
      regulate target gene expression in the diverse vulval cell types. For example,
      egl-38 (Pax2/5/8) stabilizes the vulF fate by positively regulating vulF
      characteristics and by inhibiting characteristics associated with the neighboring
      vulE cells. nhr-67 and egl-38 regulate cog-1, helping restrict its expression to
      vulE. Computational approaches have been successfully used to identify functional
      cis-regulatory motifs in the zmp-1 (zinc metalloproteinase) promoter. These
      results provide an overview of the regulatory network architecture for each
      vulval cell type.

PMID- 19104048
TI  - Structural basis for antagonism of human interleukin 18 by poxvirus interleukin
      18-binding protein.
AB  - Human interleukin-18 (hIL-18) is a cytokine that plays an important role in
      inflammation and host defense against microbes. Its activity is regulated in vivo
      by a naturally occurring antagonist, the human IL-18-binding protein (IL-18BP).
      Functional homologs of human IL-18BP are encoded by all orthopoxviruses,
      including variola virus, the causative agent of smallpox. They contribute to
      virulence by suppressing IL-18-mediated immune responses. Here, we describe the
      2.0-A resolution crystal structure of an orthopoxvirus IL-18BP, ectromelia virus
      IL-18BP (ectvIL-18BP), in complex with hIL-18. The hIL-18 structure in the
      complex shows significant conformational change at the binding interface compared
      with the structure of ligand-free hIL-18, indicating that the binding is mediated
      by an induced-fit mechanism. EctvIL-18BP adopts a canonical Ig fold and interacts
      via one edge of its beta-sandwich with 3 cavities on the hIL-18 surface through
      extensive hydrophobic and hydrogen bonding interactions. Most of the ectvIL-18BP
      residues that participate in these interactions are conserved in both human and
      viral homologs, explaining their functional equivalence despite limited sequence
      homology. EctvIL-18BP blocks a putative receptor-binding site on IL-18, thus
      preventing IL-18 from engaging its receptor. Our structure provides insights into
      how IL-18BPs modulate hIL-18 activity. The revealed binding interface provides
      the basis for rational design of inhibitors against orthopoxvirus IL-18BP (for
      treating orthopoxvirus infection) or hIL-18 (for treating certain inflammatory
      and autoimmune diseases).

PMID- 19104049
TI  - Variation in dopamine genes influences responsivity of the human reward system.
AB  - In humans, dopamine neurotransmission is influenced by functional polymorphisms
      in the dopamine transporter (DAT1) and catechol-O-methyltransferase (COMT) genes.
      Here, we used event-related functional magnetic resonance imaging to directly
      investigate the neurofunctional effects of the Val(158)Met COMT and variable
      number of tandem repeat DAT1 polymorphisms on distinct components of the reward
      system in humans. The results revealed a main effect of COMT genotype in the
      ventral striatum and lateral prefrontal cortex during reward anticipation (P <
      0.001, uncorrected) and in the orbitofrontal cortex at the time of reward
      delivery (P < 0.005), met/met individuals exhibiting the highest activation. The
      main effect of DAT1 genotype was seen in robust blood-oxygen-level-dependent
      response differences in the caudate nucleus and ventral striatum during reward
      anticipation (P < 0.001) and in the lateral prefrontal cortex and midbrain at the
      time of reward delivery, with carriers of the DAT1 9-repeat allele showing the
      highest activity. Moreover, an interaction between the COMT and DAT1 genes was
      found in the ventral striatum and lateral prefrontal cortex during reward
      anticipation and in the lateral prefrontal and orbitofrontal cortices as well as
      in the midbrain at the time of reward delivery, with carriers of the DAT1 9
      repeat allele and COMT met/met allele exhibiting the highest activation,
      presumably reflecting functional change consequent to higher synaptic dopamine
      availability. Taken together, these results indicate that genetically influenced
      variations in dopamine transmission modulate the response of brain regions
      involved in anticipation and reception of rewards and suggest that these
      responses may contribute to individual differences in reward-seeking behavior and
      in predisposition to neuropsychiatric disorders.

PMID- 19104050
TI  - Genetic analysis of interactions with eukaryotic rRNA identify the mitoribosome
      as target in aminoglycoside ototoxicity.
AB  - Aminoglycoside ototoxicity has been related to a surprisingly large number of
      cellular structures and metabolic pathways. The finding that patients with
      mutations in mitochondrial rRNA are hypersusceptible to aminoglycoside-induced
      hearing loss has indicated a possible role for mitochondrial protein synthesis.
      To study the molecular interaction of aminoglycosides with eukaryotic ribosomes,
      we made use of the observation that the drug binding site is a distinct domain
      defined by the small subunit rRNA, and investigated drug susceptibility of
      bacterial hybrid ribosomes carrying various alleles of the eukaryotic decoding
      site. Compared to hybrid ribosomes with the A site of human cytosolic ribosomes,
      susceptibility of mitochondrial hybrid ribosomes to various aminoglycosides
      correlated with the relative cochleotoxicity of these drugs. Sequence alterations
      that correspond to the mitochondrial deafness mutations A1555G and C1494T
      increased drug-binding and rendered the ribosomal decoding site hypersusceptible
      to aminoglycoside-induced mistranslation and inhibition of protein synthesis. Our
      results provide experimental support for aminoglycoside-induced dysfunction of
      the mitochondrial ribosome. We propose a pathogenic mechanism in which
      interference of aminoglycosides with mitochondrial protein synthesis exacerbates
      the drugs' cochlear toxicity, playing a key role in sporadic dose-dependent and
      genetically inherited, aminoglycoside-induced deafness.

PMID- 19104051
TI  - The Drosophila cell adhesion molecule klingon is required for long-term memory
      formation and is regulated by Notch.
AB  - The ruslan (rus) mutant was previously identified in a behavioral screen for
      mutants defective in long-lasting memory, which consists of two consolidated
      memory types, anesthesia-resistant memory, and protein synthesis-dependent long
      term memory (LTM). We demonstrate here that rus is a new allele of klingon (klg),
      which encodes a homophilic cell adhesion molecule. Klg is acutely required for
      LTM but not anesthesia-resistant memory formation, and Klg expression increases
      upon LTM induction. LTM formation also requires activity of the Notch cell
      surface receptor. Although defects in Notch have been implicated in memory loss
      because of Alzheimer's disease, downstream signaling linking Notch to memory have
      not been determined. Strikingly, we found that Notch activity increases upon LTM
      induction and regulates Klg expression. Furthermore, Notch-induced enhancement of
      LTM is disrupted by a klg mutation. We propose that Klg is a downstream effector
      of Notch signaling that links Notch activity to memory.

PMID- 19104053
TI  - Properties of developmental gene regulatory networks.
AB  - The modular components, or subcircuits, of developmental gene regulatory networks
      (GRNs) execute specific developmental functions, such as the specification of
      cell identity. We survey examples of such subcircuits and relate their structures
      to corresponding developmental functions. These relations transcend organisms and
      genes, as illustrated by the similar structures of the subcircuits controlling
      the specification of the mesectoderm in the Drosophila embryo and the
      endomesoderm in the sea urchin, even though the respective subcircuits are
      composed of nonorthologous regulatory genes.

PMID- 19104052
TI  - Replication protein A and proliferating cell nuclear antigen coordinate DNA
      polymerase selection in 8-oxo-guanine repair.
AB  - The adenine misincorporated by replicative DNA polymerases (pols) opposite 7,8
      dihydro-8-oxoguanine (8-oxo-G) is removed by a specific glycosylase, leaving the
      lesion on the DNA. Subsequent incorporation of C opposite 8-oxo-G on the
      resulting 1-nt gapped DNA is essential for the removal of the 8-oxo-G to prevent
      G-C to T-A transversion mutations. By using model DNA templates, purified DNA
      pols beta and lambda and knockout cell extracts, we show here that the auxiliary
      proteins replication protein A and proliferating cell nuclear antigen act as
      molecular switches to activate the DNA pol lambda- dependent highly efficient and
      faithful repair of A:8-oxo-G mismatches in human cells and to repress DNA pol
      beta activity. By using an immortalized human fibroblast cell line that has the
      potential to induce cancer in mice, we show that the development of a tumoral
      phenotype in these cells correlated with a differential expression of DNA pols
      lambda and beta.

PMID- 19104054
TI  - A gene regulatory network armature for T lymphocyte specification.
AB  - Choice of a T lymphoid fate by hematopoietic progenitor cells depends on
      sustained Notch-Delta signaling combined with tightly regulated activities of
      multiple transcription factors. To dissect the regulatory network connections
      that mediate this process, we have used high-resolution analysis of regulatory
      gene expression trajectories from the beginning to the end of specification,
      tests of the short-term Notch dependence of these gene expression changes, and
      analyses of the effects of overexpression of two essential transcription factors,
      namely PU.1 and GATA-3. Quantitative expression measurements of >50 transcription
      factor and marker genes have been used to derive the principal components of
      regulatory change through which T cell precursors progress from primitive
      multipotency to T lineage commitment. Our analyses reveal separate contributions
      of Notch signaling, GATA-3 activity, and down-regulation of PU.1. Using
      BioTapestry (www.BioTapestry.org), the results have been assembled into a draft
      gene regulatory network for the specification of T cell precursors and the choice
      of T as opposed to myeloid/dendritic or mast-cell fates. This network also
      accommodates effects of E proteins and mutual repression circuits of Gfi1 against
      Egr-2 and of TCF-1 against PU.1 as proposed elsewhere, but requires additional
      functions that remain unidentified. Distinctive features of this network
      structure include the intense dose dependence of GATA-3 effects, the gene
      specific modulation of PU.1 activity based on Notch activity, the lack of direct
      opposition between PU.1 and GATA-3, and the need for a distinct, late-acting
      repressive function or functions to extinguish stem and progenitor-derived
      regulatory gene expression.

PMID- 19104055
TI  - Regulatory logic of neuronal diversity: terminal selector genes and selector
      motifs.
AB  - Individual neuronal cell types are defined by the expression of unique batteries
      of terminal differentiation genes. The elucidation of the cis-regulatory
      architecture of several distinct, single neuron type-specific gene batteries in
      Caenorhabditis elegans has revealed a strikingly simple cis-regulatory logic, in
      which small cis-regulatory motifs are activated in postmitotic neurons by
      autoregulating transcription factors (TFs). Loss of the TFs results in the loss
      of the identity of the individual neuron type. I propose to term these TFs
      "terminal selector genes" and their cognate cis-regulatory target sites "terminal
      selector motifs." Terminal selector genes assign individual neuronal identities
      by directly controlling the expression of downstream, terminal differentiation
      genes and act in specific regulatory network configurations. The simplicity of
      the cis-regulatory logic on which the terminal selector gene concept is based may
      contribute to the evolvability of neuronal diversity.

PMID- 19104056
TI  - Circuitry-based gene expression profiles in GABA cells of the trisynaptic pathway
      in schizophrenics versus bipolars.
AB  - Significant reductions in GABAergic cell numbers and/or activity have been
      demonstrated in the hippocampus of subjects with schizophrenia and bipolar
      disorder. To understand how different subpopulations of interneurons are
      regulated, laser microdissection and gene expression profiling have been used to
      "deconstruct" the trisynaptic pathway, so that subtypes of GABA cells could be
      defined by their location in various layers of CA3/2 and CA1. The results suggest
      that the cellular endophenotypes for SZ and BD may be determined by multiple
      factors that include unique susceptibility genes for the respective disorders and
      altered integration among hippocampal GABA cells with extrinsic and intrinsic
      afferent fiber systems. The extensive and intricate data that has come from this
      study has provided insights into how a complex circuit, like the trisynaptic
      pathway, may be regulated in human hippocampus in both health and disease.

PMID- 19104057
TI  - Targeting Nrf2 with the triterpenoid CDDO-imidazolide attenuates cigarette smoke
      induced emphysema and cardiac dysfunction in mice.
AB  - Chronic obstructive pulmonary disease (COPD), which comprises emphysema and
      chronic bronchitis resulting from prolonged exposure to cigarette smoke (CS), is
      a major public health burden with no effective treatment. Emphysema is also
      associated with pulmonary hypertension, which can progress to right ventricular
      failure, an important cause of morbidity and mortality among patients with COPD.
      Nuclear erythroid 2 p45 related factor-2 (Nrf2) is a redox-sensitive
      transcription factor that up-regulates a battery of antioxidative genes and
      cytoprotective enzymes that constitute the defense against oxidative stress.
      Recently, it has been shown that patients with advanced COPD have a decline in
      expression of the Nrf2 pathway in lungs, suggesting that loss of this
      antioxidative protective response is a key factor in the pathophysiological
      progression of emphysema. Furthermore, genetic disruption of Nrf2 in mice causes
      early-onset and severe emphysema. The present study evaluated whether the
      strategy of activation of Nrf2 and its downstream network of cytoprotective genes
      with a small molecule would attenuate CS-induced oxidative stress and emphysema.
      Nrf2(+/+) and Nrf2(-/-) mice were fed a diet containing the potent Nrf2
      activator, 1-[2-cyano-3-,12-dioxooleana-1,9(11)-dien-28-oyl]imidazole (CDDO-Im),
      while being exposed to CS for 6 months. CDDO-Im significantly reduced lung
      oxidative stress, alveolar cell apoptosis, alveolar destruction, and pulmonary
      hypertension in Nrf2(+/+) mice caused by chronic exposure to CS. This protection
      from CS-induced emphysema depended on Nrf2, as Nrf2(-/-) mice failed to show
      significant reduction in alveolar cell apoptosis and alveolar destruction after
      treatment with CDDO-Im. These results suggest that targeting the Nrf2 pathway
      during the etiopathogenesis of emphysema may represent an important approach for
      prophylaxis against COPD.

PMID- 19104058
TI  - Dividing glial cells maintain differentiated properties including complex
      morphology and functional synapses.
AB  - It is generally believed that dividing cells gain complex features of
      differentiation only after exiting the cell cycle because cell division and
      differentiation are both under such tight regulation that their coexistence is
      deemed unlikely. As the major proliferating cell type in the mammalian CNS, NG2
      glial cells (NG2 cells) account for 5-8% of the glial cell population and form
      synaptic contacts with neurons. Here we report that NG2 cells divide while
      maintaining their differentiation, including morphological features, such as the
      elaboration of multiple complex cellular processes and physiological features
      including active glutamatergic and GABAergic synaptic responses. Not only do NG2
      cells continue to receive excitatory and inhibitory synaptic inputs as they
      undergo mitosis, a subpopulation of dividing NG2 cells can fire action potentials
      upon depolarization, thereby revealing that these dividing NG2 cells retain
      voltage-gated ion channels as well as transmitter receptors for signal
      processing. These findings provide a clear counterexample of the widely perceived
      incompatibility between cell division and differentiation.

PMID- 19104059
TI  - Dissecting early regulatory relationships in the lamprey neural crest gene
      network.
AB  - The neural crest, a multipotent embryonic cell type, originates at the border
      between neural and nonneural ectoderm. After neural tube closure, these cells
      undergo an epithelial-mesenchymal transition, migrate to precise, often distant
      locations, and differentiate into diverse derivatives. Analyses of expression and
      function of signaling and transcription factors in higher vertebrates has led to
      the proposal that a neural crest gene regulatory network (NC-GRN) orchestrates
      neural crest formation. Here, we interrogate the NC-GRN in the lamprey, taking
      advantage of its slow development and basal phylogenetic position to resolve
      early inductive events, 1 regulatory step at the time. To establish regulatory
      relationships at the neural plate border, we assess relative expression of 6
      neural crest network genes and effects of individually perturbing each on the
      remaining 5. The results refine an upstream portion of the NC-GRN and reveal
      unexpected order and linkages therein; e.g., lamprey AP-2 appears to function
      early as a neural plate border rather than a neural crest specifier and in a
      pathway linked to MsxA but independent of ZicA. These findings provide an
      ancestral framework for performing comparative tests in higher vertebrates in
      which network linkages may be more difficult to resolve because of their rapid
      development.

PMID- 19104060
TI  - Synteny and candidate gene prediction using an anchored linkage map of Astyanax
      mexicanus.
AB  - The blind Mexican cave tetra, Astyanax mexicanus, is a unique model system for
      the study of parallelism and the evolution of cave-adapted traits. Understanding
      the genetic basis for these traits has recently become feasible thanks to
      production of a genome-wide linkage map and quantitative trait association
      analyses. The selection of suitable candidate genes controlling quantitative
      traits remains challenging, however, in the absence of a physical genome. Here,
      we describe the integration of multiple linkage maps generated in four separate
      crosses between surface, cave, and hybrid forms of A. mexicanus. We performed
      exhaustive BLAST analyses of genomic markers populating this integrated map
      against sequenced genomes of numerous taxa, ranging from yeast to amniotes. We
      found the largest number of identified sequences (228), with the most expect (E)
      values <10(-5) (95), in the zebrafish Danio rerio. The most significant hits were
      assembled into an "anchored" linkage map with Danio, revealing numerous regions
      of conserved synteny, many of which are shared across critical regions of
      identified quantitative trait loci (QTL). Using this anchored map, we predicted
      the positions of 21 test genes on the integrated linkage map and verified that 18
      of these are found in locations homologous to their chromosomal positions in D.
      rerio. The anchored map allowed the identification of four candidate genes for
      QTL relating to rib number and eye size. The map we have generated will greatly
      accelerate the production of viable lists of additional candidate genes involved
      in the development and evolution of cave-specific traits in A. mexicanus.

PMID- 19104061
TI  - Redundant mechanisms mediate bristle patterning on the Drosophila thorax.
AB  - The thoracic bristle pattern of Drosophila results from the spatially restricted
      expression of the achaete-scute (ac-sc) genes in clusters of cells, mediated by
      the activity of many discrete cis-regulatory sequences. However, ubiquitous
      expression of sc or asense (ase) achieved with a heterologous promoter, in the
      absence of endogenous ac-sc expression, and the activity of the cis-regulatory
      elements, allows the development of bristles positioned at wild-type locations.
      We demonstrate that the products of the genes stripe, hairy, and
      extramacrochaetae contribute to rescue by antagonizing the activity of Sc and
      Ase. The three genes are expressed in specific but overlapping spatial domains of
      expression that form a prepattern that allows precise positioning of bristles.
      The redundant mechanisms might contribute to the robustness of the pattern. We
      discuss the possibility that patterning in trans by antagonism is ancestral and
      that the positional cis-regulatory sequences might be of recent origin.

PMID- 19104062
TI  - Slow peptide bond formation by proline and other N-alkylamino acids in
      translation.
AB  - Proteins are made from 19 aa and, curiously, one N-alkylamino acid ("imino
      acid"), proline (Pro). Pro is thought to be incorporated by the translation
      apparatus at the same rate as the 19 aa, even though the alkyl group in Pro
      resides directly on the nitrogen nucleophile involved in peptide bond formation.
      Here, by combining quench-flow kinetics and charging of tRNAs with cognate and
      noncognate amino acids, we find that Pro incorporates in translation
      significantly more slowly than Phe or Ala and that other N-alkylamino acids
      incorporate much more slowly. Our results show that the slowest step in
      incorporation of N-alkylamino acids is accommodation/peptidyl transfer after GTP
      hydrolysis on EF-Tu. The relative incorporation rates correlate with expectations
      from organic chemistry, suggesting that amino acid sterics and basicities affect
      translation rates at the peptidyl transfer step. Cognate isoacceptor tRNAs speed
      Pro incorporation to rates compatible with in vivo, although still 3-6 times
      slower than Phe incorporation from Phe-tRNA(Phe) depending on the Pro codon.
      Results suggest that Pro is the only N-alkylamino acid in the genetic code
      because it has a privileged cyclic structure that is more reactive than other N
      alkylamino acids. Our data on the variation of the rate of incorporation of Pro
      from native Pro-tRNA(Pro) isoacceptors at 4 different Pro codons help explain
      codon bias not accounted for by the "tRNA abundance" hypothesis.

PMID- 19104064
TI  - Transgenic rice plants that overexpress transcription factors RF2a and RF2b are
      tolerant to rice tungro virus replication and disease.
AB  - Rice tungro disease (RTD) is a significant yield constraint in rice-growing areas
      of South and Southeast Asia. Disease symptoms are caused largely by infection by
      the rice tungro bacilliform virus (RTBV). Two host transcription factors, RF2a
      and RF2b, regulate expression of the RTBV promoter and are important for plant
      development. Expression of a dominant negative mutant of these factors in
      transgenic rice resulted in phenotypes that mimic the symptoms of RTD, whereas
      overexpression of RF2a and RF2b had essentially no impact on plant development.
      Conversely, lines with elevated expression of RF2a or RF2b showed weak or no
      symptoms of infection after Agrobacterium inoculation of RTBV, whereas control
      plants showed severe stunting and leaf discoloration. Furthermore, transgenic
      plants exhibited reduced accumulation of RTBV RNA and viral DNA compared with
      nontransgenic plants. Similar results were obtained in studies after virus
      inoculation by green leafhoppers. Gaining disease resistance by elevating the
      expression of host regulators provides another strategy against RTD and may have
      implications for other pararetrovirus infections.

PMID- 19104065
TI  - Gene regulatory network subcircuit controlling a dynamic spatial pattern of
      signaling in the sea urchin embryo.
AB  - We dissect the transcriptional regulatory relationships coordinating the dynamic
      expression patterns of two signaling genes, wnt8 and delta, which are central to
      specification of the sea urchin embryo endomesoderm. cis-Regulatory analysis
      shows that transcription of the gene encoding the Notch ligand Delta is activated
      by the widely expressed Runx transcription factor, but spatially restricted by
      HesC-mediated repression through a site in the delta 5'UTR. Spatial transcription
      of the hesC gene, however, is controlled by Blimp1 repression. Blimp1 thus
      represses the repressor of delta, thereby permitting its transcription. The
      blimp1 gene is itself linked into a feedback circuit that includes the wnt8
      signaling ligand gene, and we showed earlier that this circuit generates an
      expanding torus of blimp1 and wnt8 expression. The finding that delta expression
      is also controlled at the cis-regulatory level by the blimp1-wnt8 torus
      generating subcircuit now explains the progression of Notch signaling from the
      mesoderm to the endoderm of the developing embryo. Thus the specific cis
      regulatory linkages of the gene regulatory network encode the coordinated spatial
      expression of Wnt and Notch signaling as they sweep outward across the vegetal
      plate of the embryo.

PMID- 19104067
TI  - Imaging the glycome.
AB  - Molecular imaging enables visualization of specific molecules in vivo and without
      substantial perturbation to the target molecule's environment. Glycans are
      appealing targets for molecular imaging but are inaccessible with conventional
      approaches. Classic methods for monitoring glycans rely on molecular recognition
      with probe-bearing lectins or antibodies, but these techniques are not well
      suited to in vivo imaging. In an emerging strategy, glycans are imaged by
      metabolic labeling with chemical reporters and subsequent ligation to fluorescent
      probes. This technique has enabled visualization of glycans in living cells and
      in live organisms such as zebrafish. Molecular imaging with chemical reporters
      offers a new avenue for probing changes in the glycome that accompany development
      and disease.

PMID- 19104068
TI  - Transformation and isolation of allelic exchange mutants of Chlamydia psittaci
      using recombinant DNA introduced by electroporation.
AB  - To facilitate genetic investigations in the obligate intracellular pathogens
      Chlamydia, the ability to construct variants by homologous recombination was
      investigated in C. psittaci 6BC. The single rRNA operon was targeted with a
      synthetic 16S rRNA allele, harboring three nucleotide substitutions over 398 bp,
      which imparts resistance to kasugamycin (Ksm) and spectinomycin (Spc) and causes
      loss of one HpaI restriction site. A fourth, silent mutation was introduced 654
      bp downstream in the beginning of the 23S rRNA gene. C. psittaci 6BC infectious
      particles were electroporated with various concentrations of circular or
      linearized plasmids containing different lengths of the rRNA region homologous to
      the chromosomal copy except for the four nucleotide substitutions. Ksm and Spc
      were added 18 h after inoculation onto confluent cell monolayers in the plaque
      assay. Resistant plaques were picked and expanded with selection 10 days later
      before collecting DNA for analysis by PCR, restriction mapping, sequencing, or
      Southern. Spontaneous resistance to Ksm and Spc was never observed in mock
      electroporated bacteria (frequency <6.2 x 10(-9)). Conversely, double resistance
      and replacement of the 16S rRNA gene were observed when C. psittaci was
      electroporated with the recombination substrates. Highest efficiency was obtained
      with 10 microg of circular vector prepared in a DNA methylase-deficient
      Escherichia coli (1.9 +/- 1.1 x 10(-6), n = 7). Coinheritance of the silent 23S
      rRNA mutation was seen in 46 of 67 recombinants analyzed, illustrating DNA
      exchange of up to 1,052 bp in length. These findings provide the first step
      toward genetic manipulation of Chlamydia.

PMID- 19104070
TI  - Imaging quantum confinement with optical and POWER (perturbations observed with
      enhanced resolution) NMR.
AB  - The nanoscale distributions of electron density and electric fields in GaAs
      semiconductor devices are displayed with NMR experiments. The spectra are
      sensitive to the changes to the nuclear-spin Hamiltonian that are induced by
      perturbations delivered in synchrony with a line-narrowing pulse sequence. This
      POWER (perturbations observed with enhanced resolution) method enhanced
      resolution up to 10(3)-fold, revealing the distribution of perturbations over
      nuclear sites. Combining this method with optical NMR, we imaged quantum-confined
      electron density in an individual AlGaAs/GaAs heterojunction via hyperfine
      shifts. Fits to the coherent evolution and relaxation of nuclei within a
      hydrogenic state established one-to-one correspondence of radial position to
      frequency. Further experiments displayed the distribution of photo-induced
      electric field within the same states via a quadrupolar Stark effect. These
      unprecedented high-resolution distributions discriminate between competing models
      for the luminescence and support an excitonic state, perturbed by the interface,
      as the dominant source of the magnetically modulated luminescence.

PMID- 19104071
TI  - Molecular mechanism for the umami taste synergism.
AB  - Umami is one of the 5 basic taste qualities. The umami taste of L-glutamate can
      be drastically enhanced by 5' ribonucleotides and the synergy is a hallmark of
      this taste quality. The umami taste receptor is a heteromeric complex of 2 class
      C G-protein-coupled receptors, T1R1 and T1R3. Here we elucidate the molecular
      mechanism of the synergy using chimeric T1R receptors, site-directed mutagenesis,
      and molecular modeling. We propose a cooperative ligand-binding model involving
      the Venus flytrap domain of T1R1, where L-glutamate binds close to the hinge
      region, and 5' ribonucleotides bind to an adjacent site close to the opening of
      the flytrap to further stabilize the closed conformation. This unique mechanism
      may apply to other class C G-protein-coupled receptors.

PMID- 19104072
TI  - Nitrogen catabolite repression-sensitive transcription as a readout of Tor
      pathway regulation: the genetic background, reporter gene and GATA factor assayed
      determine the outcomes.
AB  - Nitrogen catabolite repression (NCR)-sensitive genes, whose expression is highly
      repressed when provided with excess nitrogen and derepressed when nitrogen is
      limited or cells are treated with rapamycin, are routinely used as reporters in
      mechanistic studies of the Tor signal transduction pathway in Saccharomyces
      cerevisiae. Two GATA factors, Gln3 and Gat1, are responsible for NCR-sensitive
      transcription, but recent evidence demonstrates that Tor pathway regulation of
      NCR-sensitive transcription bifurcates at the level of GATA factor localization.
      Gln3 requires Sit4 phosphatase for nuclear localization and NCR-sensitive
      transcription while Gat1 does not. In this article, we demonstrate that the
      extent to which Sit4 plays a role in NCR-sensitive transcription depends upon
      whether or not (i) Gzf3, a GATA repressor homologous to Dal80, is active in the
      genetic background assayed; (ii) Gat1 is able to activate transcription of the
      assayed gene in the absence of Gln3 in that genetic background; and (iii) the
      gene chosen as a reporter is able to be transcribed by Gln3 or Gat1 in the
      absence of the other GATA factor. Together, the data indicate that in the absence
      of these three pieces of information, overall NCR-sensitive gene transcription
      data are unreliable as Tor pathway readouts.

PMID- 19104073
TI  - Characterization of demographic expansions from pairwise comparisons of linked
      microsatellite haplotypes.
AB  - This work extends the methods of demographic inference based on the distribution
      of pairwise genetic differences between individuals (mismatch distribution) to
      the case of linked microsatellite data. Population genetics theory describes the
      distribution of mutations among a sample of genes under different demographic
      scenarios. However, the actual number of mutations can rarely be deduced from DNA
      polymorphisms. The inclusion of mutation models in theoretical predictions can
      improve the performance of statistical methods. We have developed a maximum
      pseudolikelihood estimator for the parameters that characterize a demographic
      expansion for a series of linked loci evolving under a stepwise mutation model.
      Those loci would correspond to DNA polymorphisms of linked microsatellites (such
      as those found on the Y chromosome or the chloroplast genome). The proposed
      method was evaluated with simulated data sets and with a data set of chloroplast
      microsatellites that showed signal for demographic expansion in a previous study.
      The results show that inclusion of a mutational model in the analysis improves
      the estimates of the age of expansion in the case of older expansions.

PMID- 19104074
TI  - Mutations in the chromosomal passenger complex and the condensin complex
      differentially affect synaptonemal complex disassembly and metaphase I
      configuration in Drosophila female meiosis.
AB  - Production of haploid gametes relies on the specially regulated meiotic cell
      cycle. Analyses of the role of essential mitotic regulators in meiosis have been
      hampered by a shortage of appropriate alleles in metazoans. We characterized
      female-sterile alleles of the condensin complex component dcap-g and used them to
      define roles for condensin in Drosophila female meiosis. In mitosis, the
      condensin complex is required for sister-chromatid resolution and contributes to
      chromosome condensation. In meiosis, we demonstrate a role for dcap-g in
      disassembly of the synaptonemal complex and for proper retention of the
      chromosomes in a metaphase I-arrested state. The chromosomal passenger complex
      also is known to have mitotic roles in chromosome condensation and is required in
      some systems for localization of the condensin complex. We used the QA26 allele
      of passenger component incenp to investigate the role of the passenger complex in
      oocyte meiosis. Strikingly, in incenp(QA26) mutants maintenance of the
      synaptonemal complex is disrupted. In contrast to the dcap-g mutants, the incenp
      mutation leads to a failure of paired homologous chromosomes to biorient, such
      that bivalents frequently orient toward only one pole in prometaphase and
      metaphase I. We show that incenp interacts genetically with ord, suggesting an
      important functional relationship between them in meiotic chromosome dynamics.
      The dcap-g and incenp mutations cause maternal effect lethality, with embryos
      from mutant mothers arrested in the initial mitotic divisions.

PMID- 19104075
TI  - Nonadditive expression of homoeologous genes is established upon polyploidization
      in hexaploid wheat.
AB  - Effects of polyploidy in allohexaploid wheat (Triticum aestivum L.) have
      primarily been ascribed to increases in coding sequence variation and potential
      to acquire new gene functions through mutation of redundant loci. However,
      regulatory variation that arises through new promoter and transcription factor
      combinations or epigenetic events may also contribute to the effects of
      polyploidization. In this study, gene expression was characterized in a synthetic
      T. aestivum line and the T. turgidum and Aegilops tauschii parents to establish a
      timeline for such regulatory changes and estimate the frequency of nonadditive
      expression of homoeologous transcripts in newly formed T. aestivum. Large-scale
      analysis of nonadditive gene expression was assayed by microarray expression
      experiments, where synthetic T. aestivum gene expression was compared to additive
      model values (mid-parent) calculated from parental T. turgidum and Ae. tauschii
      expression levels. Approximately 16% of genes were estimated to display
      nonadditive expression in synthetic T. aestivum. A certain fraction of the genes
      (2.9%) showed overdominance or underdominance. cDNA-single strand conformation
      polymorphism analysis was applied to measure expression of homoeologous
      transcripts and further verify microarray data. The results demonstrate that
      allopolyploidization, per se, results in rapid initiation of differential
      expression of homoeologous loci and nonadditive gene expression in T. aestivum.

PMID- 19104076
TI  - The a2 mating-type locus genes lga2 and rga2 direct uniparental mitochondrial DNA
      (mtDNA) inheritance and constrain mtDNA recombination during sexual development
      of Ustilago maydis.
AB  - Uniparental inheritance of mitochondria dominates among sexual eukaryotes.
      However, little is known about the mechanisms and genetic determinants. We have
      investigated the role of the plant pathogen Ustilago maydis genes lga2 and rga2
      in uniparental mitochondrial DNA (mtDNA) inheritance during sexual development.
      The lga2 and rga2 genes are specific to the a2 mating-type locus and encode small
      mitochondrial proteins. On the basis of identified sequence polymorphisms due to
      variable intron numbers in mitochondrial genotypes, we could demonstrate that
      lga2 and rga2 decisively influence mtDNA inheritance in matings between a1 and a2
      strains. Deletion of lga2 favored biparental inheritance and generation of
      recombinant mtDNA molecules in combinations in which inheritance of mtDNA of the
      a2 partner dominated. Conversely, deletion of rga2 resulted in predominant loss
      of a2-specific mtDNA and favored inheritance of the a1 mtDNA. Furthermore,
      expression of rga2 in the a1 partner protected the associated mtDNA from
      elimination. Our results indicate that Lga2 in conjunction with Rga2 directs
      uniparental mtDNA inheritance by mediating loss of the a1-associated mtDNA. This
      study shows for the first time an interplay of mitochondrial proteins in
      regulating uniparental mtDNA inheritance.

PMID- 19104078
TI  - A model selection approach for the identification of quantitative trait loci in
      experimental crosses, allowing epistasis.
AB  - The identification of quantitative trait loci (QTL) and their interactions is a
      crucial step toward the discovery of genes responsible for variation in
      experimental crosses. The problem is best viewed as one of model selection, and
      the most important aspect of the problem is the comparison of models of different
      sizes. We present a penalized likelihood approach, with penalties on QTL and
      pairwise interactions chosen to control false positive rates. This extends the
      work of Broman and Speed to allow for pairwise interactions among QTL. A
      conservative version of our penalized LOD score provides strict control over the
      rate of extraneous QTL and interactions; a more liberal criterion is more lenient
      on interactions but seeks to maintain control over the rate of inclusion of false
      loci. The key advance is that one needs only to specify a target false positive
      rate rather than a prior on the number of QTL and interactions. We illustrate the
      use of our model selection criteria as exploratory tools; simulation studies
      demonstrate reasonable power to detect QTL. Our liberal criterion is comparable
      in power to two Bayesian approaches.

PMID- 19104079
TI  - Characterization of chromosome ends in the filamentous fungus Neurospora crassa.
AB  - Telomeres and subtelomere regions have vital roles in cellular homeostasis and
      can facilitate niche adaptation. However, information on telomere/subtelomere
      structure is still limited to a small number of organisms. Prior to initiation of
      this project, the Neurospora crassa genome assembly contained only 3 of the 14
      telomeres. The missing telomeres were identified through bioinformatic mining of
      raw sequence data from the genome project and from clones in new cosmid and
      plasmid libraries. Their chromosomal locations were assigned on the basis of
      paired-end read information and/or by RFLP mapping. One telomere is attached to
      the ribosomal repeat array. The remaining chromosome ends have atypical
      structures in that they lack distinct subtelomere domains or other sequence
      features that are associated with telomeres in other organisms. Many of the
      chromosome ends terminate in highly AT-rich sequences that appear to be products
      of repeat-induced point mutation, although most are not currently repeated
      sequences. Several chromosome termini in the standard Oak Ridge wild-type strain
      were compared to their counterparts in an exotic wild type, Mauriceville. This
      revealed that the sequences immediately adjacent to the telomeres are usually
      genome specific. Finally, despite the absence of many features typically found in
      the telomere regions of other organisms, the Neurospora chromosome termini still
      retain the dynamic nature that is characteristic of chromosome ends.

PMID- 19104077
TI  - Multilocus patterns of nucleotide diversity, population structure and linkage
      disequilibrium in Boechera stricta, a wild relative of Arabidopsis.
AB  - Information about polymorphism, population structure, and linkage disequilibrium
      (LD) is crucial for association studies of complex trait variation. However, most
      genomewide studies have focused on model systems, with very few analyses of
      undisturbed natural populations. Here, we sequenced 86 mapped nuclear loci for a
      sample of 46 genotypes of Boechera stricta and two individuals of B. holboellii,
      both wild relatives of Arabidopsis. Isolation by distance was significant across
      the species range of B. stricta, and three geographic groups were identified by
      structure analysis, principal coordinates analysis, and distance-based phylogeny
      analyses. The allele frequency spectrum indicated a genomewide deviation from an
      equilibrium neutral model, with silent nucleotide diversity averaging 0.004. LD
      decayed rapidly, declining to background levels in approximately 10 kb or less.
      For tightly linked SNPs separated by <1 kb, LD was dependent on the reference
      population. LD was lower in the specieswide sample than within populations,
      suggesting that low levels of LD found in inbreeding species such as B. stricta,
      Arabidopsis thaliana, and barley may result from broad geographic sampling that
      spans heterogeneous genetic groups. Finally, analyses also showed that inbreeding
      B. stricta and A. thaliana have approximately 45% higher recombination per
      kilobase than outcrossing A. lyrata.

PMID- 19104082
TI  - Cytokine-induced human IFN-gamma-secreting effector-memory Th cells in chronic
      autoimmune inflammation.
AB  - T-helper (Th) cells activated by cytokines in the absence of T-cell receptor
      ligation are suspected to participate in inflammatory processes by production of
      interferon-gamma (IFN-gamma). Still, the relevance of such a mechanism has not
      been addressed in humans. Here we demonstrate that a subset of human effector
      memory Th cells expressing functional interleukin-12R (IL-12R), IL-18Ralpha, and
      CCR5 ex vivo can be induced to secrete IFN-gamma by cytokines signaling via the
      IL-2R common gamma-chain in combination with IL-12 and IL-18. Cytokine-driven IFN
      gamma production depends on JAK3- and p38 mitogen-activated kinase signals and is
      sensitive to suppression by CD25(++) regulatory T cells. Contrary to IFN-gamma(+)
      Th cells induced upon antigen-specific stimulation, their cytokine-activated
      counterparts characteristically lack expression of costimulator 4-1BB (CD137).
      Strikingly, the majority of Th cells infiltrating inflamed joints of rheumatoid
      arthritis patients is equipped with receptors prerequisite for cytokine-induced
      IFN-gamma secretion. Among these cells, we detected a substantial fraction that
      secretes IFN-gamma directly ex vivo but lacks 4-1BB expression, indicating that
      cytokine-induced IFN-gamma(+) Th cells operate in autoimmune inflammation. Our
      data provide a rationale for how human effector-memory Thcells can participate in
      perpetuating inflammatory processes in autoimmunity even in the absence of T-cell
      receptor ligation.

PMID- 19104081
TI  - Differential requirement for the activation of the inflammasome for processing
      and release of IL-1beta in monocytes and macrophages.
AB  - The processing of pro-interleukin-1beta depends on activation of caspase-1.
      Controversy has arisen whether Toll-like receptor (TLR) ligands alone can
      activate caspase-1 for release of interleukin-1beta (IL-1beta). Here we
      demonstrate that human blood monocytes release processed IL-1beta after a one
      time stimulation with either TLR2 or TLR4 ligands, resulting from constitutively
      activated caspase-1 and release of endogenous adenosine triphosphate. The
      constitutive activation of caspase-1 depends on the inflammasome components,
      apoptosis-associated speck-like protein containing a caspase recruitment domain
      (ASC), and NALP3, but in monocytes caspase-1 activation is uncoupled from
      pathogen-associated molecular pattern recognition. In contrast, macrophages are
      unable to process and release IL-1beta solely by TLR ligands and require a second
      adenosine triphosphate stimulation. We conclude that IL-1beta production is
      differentially regulated in monocytes and macrophages, and this reflects their
      separate functions in host defense and inflammation.

PMID- 19104083
TI  - How well are we doing and are we doing the right thing?

PMID- 19104084
TI  - Competency in the new language of medical education.

PMID- 19104086
TI  - Use of the Valsalva manoeuvre in the prehospital setting: a review of the
      literature.
AB  - BACKGROUND: The Valsalva manoeuvre (VM) is used in the prehospital setting as a
      first-line treatment for managing haemodynamically stable supraventricular
      tachycardia (SVT) in the form of atrioventricular nodal re-entrant tachycardia
      (AVNRT) and atrioventricular re-entrant tachycardia (AVRT). The hospital-based
      use of this technique is supported by a number of published studies, but the
      performance and efficacy of the VM in the prehospital setting has not been
      examined. METHODS: A review of the literature via electronic databases was
      conducted. Six clinical studies examining the technique and efficacy of the VM in
      arrhythmia reversion were identified. No prehospital studies were identified.
      Significant variation in the practical application of the VM and its efficacy was
      noted. RESULTS: The literature identified three primary elements of the technique
      which affected its efficacy in reversion of SVT: a pressure of 40 mm Hg, the
      supine position and duration of 15 s. The efficacy of the VM in reversion of SVT
      is difficult to quantify in some literature owing to variations in technique and
      clinical application. The VM appears to be more successful than carotid sinus
      massage and ice-to-face techniques, and is inherently safe across all age groups.
      CONCLUSION: This review has shown that a standard of performance of the VM
      technique is defined within the medical literature, but no evidence exists to
      determine its efficacy or use in the prehospital setting. A prehospital study is
      therefore required to affirm the VM as part of prehospital clinical practice
      guidelines for SVT.

PMID- 19104087
TI  - Evaluation of the risk assessment matrix: a mental health triage tool.
AB  - BACKGROUND: The Risk Assessment Matrix (RAM) is a mental health triage tool
      designed to assist emergency department (ED) staff to make rapid and accurate
      assessment of a patient with a suspected or actual mental health problem, and to
      identify patients at immediate risk of self-harm. A study was conducted to
      evaluate the effectiveness of this triage tool. METHODS: Using a naturalistic
      retrospective study design, all patients attending the ED with an actual or
      suspected mental health problem over a 2-month period were identified to
      determine if any association existed with the level of risk ascertained at
      assessment by ED staff using the RAM and the patient's final outcome of their
      management. A questionnaire was administered to ED staff to determine face and
      content validity. RESULTS: 202 patients were identified, 155 of whom met the
      inclusion criteria. Those classified medium or high risk by ED staff were
      significantly more likely to be referred to mental health services for further
      assessment, and to be admitted to an inpatient psychiatric units or have
      involvement of home intervention/crisis teams. Analysis showed that a significant
      number of respondents found the RAM useful in making triage and ongoing
      management decisions, indicating that the tool had strong face and content
      validity. CONCLUSION: A preliminary interpretation of the results of this study
      suggests the RAM is sensitive in identifying patients who warrant further urgent
      mental health intervention and is an effective mental health triage tool. Further
      prospective studies are needed to provide a more robust evidence base of the use
      of the RAM in the emergency setting.

PMID- 19104088
TI  - Dose versus diagnosis: iatrogenic radiation exposure by multidetector
      computerised tomography in an academic emergency department with measurement of
      clinically actionable results and emergently treatable findings.
AB  - AIM: To determine the iatrogenic absorbed dosage of radiation of the patient in
      milligray (mGy) computerised tomography dose index volume (CTDIvol) when tested
      with multidetector computerised tomography (MDCT) in the emergency department
      (ED) setting and calculate the absorbed dosage of radiation per clinically
      actionable result and emergently treatable finding (ETF). SETTING: The University
      of Texas Medical Branch (UTMB) ED located in Galveston, Texas, USA, is a level 1
      trauma and tertiary referral centre treating 70,000 patients per annum. METHOD: A
      retrospective cross-sectional data analysis of 770 emergency patients
      investigated by MDCT in July 2007. The presence of actionable results and ETF
      were determined by chart review. RESULTS: A total of 5320 emergency patients was
      treated in the UTMB ED in July 2007. This included 4508 medical and 812 trauma
      patients. A total of 1094 MDCT studies was performed, of which complete data were
      available on 1046. A total of 770 patients was investigated by MDCT, representing
      14.47% of all emergency patients. This included 33.99% of trauma patients and
      10.96% of medical patients. Actionable results were found in 341 studies and ETF
      in 105 studies. The mean radiation was 163.27 and 530.23 mGy CTDIvol for
      actionable results and ETF, respectively, for all studies. The mean radiation was
      53.27 and 106.36 mGy CTDIvol for medical and trauma patients, respectively.
      CONCLUSIONS: The absorbed dosage of radiation of patients investigated by MDCT is
      clinically significant. The actionable results and ETF in our study demonstrate
      considerable opportunity for improvement in the utilisation of this technology by
      physicians.

PMID- 19104089
TI  - Secondary spontaneous pneumothorax: indication for intercostal chest drain
      insertion?

PMID- 19104090
TI  - Excessive use of force by police: a survey of academic emergency physicians.
AB  - OBJECTIVE: To determine the clinical experience, management and training of
      emergency physicians in the suspected use of excessive force by law enforcement
      officers. METHODS: Surveys were mailed to a random sample of academic emergency
      physicians in the USA. RESULTS: Of 393 emergency physicians surveyed, 315 (80.2%)
      responded. Of the respondents, 99.8% (95% CI 98.2% to 100.0%) believed excessive
      use of force actually occurs and 97.8% (95% CI 95.5% to 99.1%) replied that they
      had managed patients with suspected excessive use of force. These incidents were
      not reported by 71.2% (95% CI 65.6% to 76.4%) of respondents, 96.5% (95% CI 93.8%
      to 98.2%) had no departmental policies and 93.7% (95% CI 90.4% to 96.1%) had not
      received training in the management of these cases. CONCLUSIONS: Suspected
      excessive use of force is encountered by academic emergency physicians in the
      USA. There is only limited training or policies for the management of these
      cases.

PMID- 19104091
TI  - Protocol compliance and time management in blunt trauma resuscitation.
AB  - OBJECTIVES: To study advanced trauma life support (ATLS) protocol adherence
      prospectively in trauma resuscitation and to analyse time management of daily
      multidisciplinary trauma resuscitation at a level 1 trauma centre, for both
      moderately and severely injured patients. PATIENTS AND METHODS: All victims of
      severe blunt trauma were consecutively included. Patients with a revised trauma
      score (RTS) of 12 were resuscitated by a "minor trauma" team and patients with an
      RTS of less than 12 were resuscitated by a "severe trauma" team. Digital video
      recordings were used to analyse protocol compliance and time management during
      initial assessment. RESULTS: From 1 May to 1 September 2003, 193 resuscitations
      were included. The "minor trauma" team assessed 119 patients, with a mean injury
      severity score (ISS) of 7 (range 1-45). Overall protocol compliance was 42%,
      ranging from 0% for thoracic percussion to 93% for thoracic auscultation. The
      median resuscitation time was 45.9 minutes (range 39.7-55.9). The "severe team"
      assessed 74 patients, with a mean ISS of 22 (range 1-59). Overall protocol
      compliance was 53%, ranging from 4% for thoracic percussion to 95% for thoracic
      auscultation. Resuscitation took 34.8 minutes median (range 21.6-44.1).
      CONCLUSION: Results showed the current trauma resuscitation to be ATLS-like, with
      sometimes very low protocol compliance rates. Timing of secondary survey and
      radiology and thus time efficiency remains a challenge in all trauma patients. To
      assess the effect of trauma resuscitation protocols on outcome, protocol
      adherence needs to be improved.

PMID- 19104092
TI  - The utility of routine laboratory testing in hypoglycaemic emergency department
      patients.
AB  - BACKGROUND: After treating a hypoglycaemic patient, how in-depth a work-up is
      required to prevent their next hypoglycaemic episode? OBJECTIVE: To determine the
      utility of routine laboratory testing in the management of hypoglycaemia.
      METHODS: A cross-sectional study at two urban teaching hospitals from July 2006
      to July 2007. The study included adult patients (> or = 18 years) with
      hypoglycaemia (fingerstick glucose < or = 60 mg/dl (3.33 mmol/l) in the emergency
      department or altered mental status resolved by glucose or glucagon). Predictor
      variables were age, gender, medical history, physical examination, hypoglycaemic
      agent (insulin vs oral hypoglycaemic). Outcome variables were electrolyte
      abnormality (serum sodium outside the range of 135-145 mmol/l; serum potassium
      outside the range of 3.5-5.0 mEq/dl), leucocytosis (white blood cell count
      >15,000/high power field) or urinary tract infection. Continuous data are
      presented as mean (SD). Categorical data are presented as percentages with 95%
      confidence intervals. Student's t and Fisher's exact tests were used to compare
      data when appropriate (alpha = 0.05, two-tailed). RESULTS: 291 patients were
      studied with a mean age of 64 years (SD 16) (range 22-95) 54 women. 200 patients
      (69%, 95% CI 63% to 74%) had at least one laboratory abnormality. These included
      newly diagnosed renal failure (23%), pre-existing renal failure (32%),
      hypokalaemia (8%), hyperkalaemia (11%), leucocytosis (4.2%) and pyuria (19%). No
      significant difference was found between the rates of abnormal laboratory results
      in patients on insulin versus those on oral hypoglycaemics. Higher admission
      rates (p = 0.001) were also observed in patients with abnormal (70%) compared
      with normal (53%) laboratory results. CONCLUSION: The high rate of laboratory
      abnormalities in hypoglycaemic patients justifies routine testing.

PMID- 19104093
TI  - The Prediction of Risk In Syncope using ECG characteristics (PRISE) pilot study:
      can heart rate variability be used to predict risk in patients presenting to the
      emergency department with syncope?
AB  - AIM: This study was conducted as a feasibility pilot for the Prediction of Risk
      In Syncope using ECG characteristics (PRISE) study. The secondary aim was to
      determine whether heart rate variability (HRV) characteristics may be useful to
      distinguish low and high-risk syncope patients. METHODS: Adult patients
      presenting to the emergency department (ED) with syncope over a one-month period
      underwent a 5-minute 12-lead ECG. Study patients were assigned high, medium or
      low-risk status according to the ED's existing syncope guidelines as well as one
      of four likely diagnostic categories. ECG signals from all patients were then
      analysed and time domain HRV characteristics were derived using WelchAllyn's
      Cardioperfect interpretation software. A control group of patients was also
      recruited. RESULTS: Over a 4-week period in July 2007, 32 patients were recruited
      into the study group and 23 into the control group. ECG tracings of five study
      group patients were not suitable for analysis. According to the ED's existing
      syncope guidelines there were nine low-risk, 12 medium-risk and six high-risk
      patients with diagnostic categories as follows: postural hypotension, five;
      vasovagal, 16; cardiac, five and other, one. Patients with cardiac syncope had
      greater mean values for all HRV characteristics except NN number and NN minimum;
      however, with overlapping confidence intervals. Low-risk patients were more
      likely to be younger than medium and high-risk patients. No HRV parameters showed
      any significant differences. CONCLUSIONS: Measuring HRV in the acute ED setting
      is feasible. If patients with cardiac and neurocardiogenic syncope have different
      HRV characteristics then it could be useful to determine a patient's underlying
      cause of syncope in the ED, which would allow earlier decision-making.

PMID- 19104094
TI  - Is propofol a safe and effective sedative for relocating hip prostheses?
AB  - OBJECTIVE: To explore the safety and efficacy of propofol as a sedative for the
      relocation of hip prostheses in the emergency department. METHODS: A prospective
      observational study was performed in 100 patients aged 37-93 years who received
      sedation with propofol in the emergency department for hip prosthetic relocation.
      All patients received intravenous titrated morphine prior to radiography,
      followed by a 1 mg/kg bolus of propofol after adequate preoxygenation. At 60 s,
      joint relocation was attempted by an independent physician. Data for each patient
      were recorded, with particular attention given to adverse outcomes. RESULTS: Two
      patients were excluded because of protocol violation. The use of propofol
      achieved hip relocation in 94 of the remaining 98 patients (96%). The four
      unsuccessful cases required general anaesthesia with muscle relaxation. Eight
      patients experienced a fall in oxygen saturation, four responding to airway
      repositioning and four requiring brief supplemental ventilation. Four patients
      became hypotensive and required titrated intravenous boluses of a vasopressor
      (metaraminol) to restore normal blood pressure. 42 patients required additional
      doses of propofol, 36 for inadequate sedation and 6 for prolonged reduction
      attempts. CONCLUSIONS: Significant adverse effects of propofol in this case
      series were uncommon (12/98 patients) and readily countered. This case series
      suggests that propofol is a safe and effective sedative for relocating hip
      prostheses.

PMID- 19104080
TI  - Disease-specific analyses of unrelated cord blood transplantation compared with
      unrelated bone marrow transplantation in adult patients with acute leukemia.
AB  - We made a disease-specific comparison of unrelated cord blood (CB) recipients and
      human leukocyte antigen allele-matched unrelated bone marrow (BM) recipients
      among 484 patients with acute myeloid leukemia (AML; 173 CB and 311 BM) and 336
      patients with acute lymphoblastic leukemia (ALL; 114 CB and 222 BM) who received
      myeloablative transplantations. In multivariate analyses, among AML cases, lower
      overall survival (hazard ratio [HR]=1.5; 95% confidence interval [CI], 1.0-2.0,
      P= .028) and leukemia-free survival (HR=1.5; 95% CI, 1.1-2.0, P= .012) were
      observed in CB recipients. The relapse rate did not differ between the 2 groups
      of AML (HR=1.2; 95% CI, 0.8-1.9, P= .38); however, the treatment-related
      mortality rate showed higher trend in CB recipients (HR=1.5; 95% CI, 1.0-2.3, P=
      .085). In ALL, there was no significant difference between the groups for relapse
      (HR=1.4, 95% CI, 0.8-2.4, P= .19) and treatment-related mortality (HR=1.0; 95%
      CI, 0.6-1.7, P= .98), which contributed to similar overall survival (HR=1.1; 95%
      CI, 0.7-1.6, P= .78) and leukemia-free survival (HR=1.2; 95% CI, 0.9-1.8, P=
      .28). Matched or mismatched single-unit CB is a favorable alternative stem cell
      source for patients without a human leukocyte antigen-matched related or
      unrelated donor. For patients with AML, decreasing mortality, especially in the
      early phase of transplantation, is required to improve the outcome for CB
      recipients.

PMID- 19104096
TI  - Paediatric distal radial fracture manipulation: multicentre analysis of process
      times.
AB  - BACKGROUND: Children with simple radial fractures requiring manipulation are
      conventionally admitted for manipulation under general anaesthesia. On the
      assumption that children (and their parents) wish to spend as little time in
      hospital as possible, a study was undertaken to explore the experience of
      children with distal radial fractures admitted for general anaesthesia. METHODS:
      A retrospective analysis was performed of the time taken from arrival at the
      emergency department (ED) to general anaesthesia and the time taken from arrival
      at the ED to hospital discharge in three centres in south-west England: the
      Bristol Children's Hospital, Derriford (Plymouth) Hospital and the Royal Devon &
      Exeter Hospital. RESULTS: The median wait for general anaesthesia was >8 h and
      the median wait from ED admission to discharge was >21 h. This compares with a
      typical arrival to discharge time for paediatric procedural sedation of 4-5 h in
      the ED of the Royal Devon & Exeter Hospital. CONCLUSIONS: Given the assumption
      that children (and their parents) wish to spend as little time in hospital as
      possible, there appears to be a role for procedural sedation in the ED for this
      group of children, with a significantly reduced turnaround time anticipated.

PMID- 19104095
TI  - Door to relocation time for dislocated hip prosthesis: multicentre comparison of
      emergency department procedural sedation versus theatre-based general
      anaesthesia.
AB  - BACKGROUND: Dislocation of a hip prosthesis is a painful event which has an
      incidence of 4% for primary total hip arthroplasty. Relocation is traditionally
      performed under general anaesthesia in the operating theatre, but relocation
      using sedation in the emergency department (ED) has been reported, with a limited
      success rate of 62%. A study was undertaken to compare door to relocation times
      for ED sedation and theatre general anaesthesia. METHODS: The notes of all
      patients attending five centres in the south west of England with prosthetic hip
      dislocation over a 12-month period between 2005 and 2006 were retrospectively
      reviewed using standardised data collection forms. RESULTS: Successful ED
      reduction was significantly quicker than failed ED reduction and theatre-based
      general anaesthesia (2 h 21 min vs 8 h 32 min; p<0.001). No statistical
      difference was found between failed ED reduction and theatre general anaesthesia.
      CONCLUSIONS: Reduction of dislocated hip prostheses in the ED saves nearly 6 h
      compared with theatre-based general anaesthesia and is therefore advocated.

PMID- 19104097
TI  - Non-reducible hip dislocation in the ED.

PMID- 19104098
TI  - Can age-based estimates of weight be safely used when resuscitating children?
AB  - BACKGROUND: Prescribing medication appropriate to a child's bodily dimensions is
      fundamental to paediatric emergency medicine. Mathematical formulae are
      frequently used in clinical practice to estimate children's weights. In 1995 the
      UK's paediatric reference data, describing age-related changes in bodily
      proportions (both weight and height), were updated and published. This study
      assesses the validity of using mathematical estimates, age-based estimates or
      length-based estimates of weight (the latter both compiled from this reference
      data) by comparison with actual physical measurements recorded in a paediatric
      clinic setting. METHODS: A prospective study was carried out in a paediatric
      outpatient setting recording age, weight and height for statistical comparison
      with these three possible methods. RESULTS: 544 children aged 0-11 years were
      recruited, with mean (SD) age, weight and height of 5.3 (2.9) years, 21.4 (10) kg
      and 108 (22) cm, respectively. CONCLUSIONS: Both length-based and age-based
      estimates of weight outperformed the currently accepted "gold standard"
      mathematical estimate when applied to children up to 11 years of age
      (approximately 35 kg). Length-based estimates were statistically superior, but
      the physical limitations and technical constraints posed when attempting to
      accurately measure a child's length in emergency environments may favour the
      simplicity of using the child's age against tables of growth chart reference data
      to provide an estimate of their weight.

PMID- 19104099
TI  - View from the emergency department trolley: fractured olecranon.
AB  - The experience of a patient with a fractured olecranon is described.

PMID- 19104100
TI  - Rectus sheath haematoma: over-diagnosis and under-diagnosis.

PMID- 19104101
TI  - A retrospective chart review of elderly patients who cannot weight bear following
      a hip injury but whose initial x rays are normal.
AB  - Falls causing hip injury are common among older people. In elderly patients who
      cannot weight bear following a hip injury but have normal initial x rays,
      management often involves admission to the clinical decision unit for analgesia,
      mobilisation and physiotherapy. A proportion of these patients require further
      investigation due to continuing pain or inability to weight bear. There is
      currently no agreed pathway for these patients, who often wait days for
      definitive diagnosis and management. Some centres suggest investigating such
      patients with magnetic resonance imaging at 24 h post-admission. This study aimed
      to define this patient group in terms of emergency management, number undergoing
      further investigation and outcome. A secondary aim was to produce a management
      pathway for these patients.

PMID- 19104103
TI  - Critical appraisal for emergency medicine: 5 Evaluation of a diagnostic test.

PMID- 19104102
TI  - Technical tutorial: How to pack a nose with bismuth iodoform paraffin paste gauze
      safely and effectively.
AB  - The current primary treatment for epistaxis in accident and emergency departments
      is the insertion of Merocel packs. If these are properly inserted, but fail to
      control bleeding, it is necessary to insert a bismuth iodoform paraffin paste
      (BIPP) pack. A BIPP pack, when properly inserted, has the potential to stop most
      bleeds, but books and journals suggest a method of insertion that limits its
      effectiveness. A safer and more effective way of packing a nose with BIPP than
      the traditional method is described.

PMID- 19104104
TI  - Towards evidence based emergency medicine: best BETs from the Manchester Royal
      Infirmary. BET 1. Topical anaesthetic and pain associated with lumbar puncture in
      neonates.

PMID- 19104106
TI  - Towards evidence based emergency medicine: best BETs from the Manchester Royal
      Infirmary. BET 2. C-reactive protein in the differential diagnosis of heart
      failure and chest infection.

PMID- 19104107
TI  - Towards evidence based emergency medicine: best BETs from the Manchester Royal
      Infirmary. BET 3. Non-invasive positive pressure ventilation for patients with
      acute exacerbations of asthma.

PMID- 19104108
TI  - Towards evidence based emergency medicine: best BETs from the Manchester Royal
      Infirmary. BET 4. Beta-blockers or digoxin for rate control of acute atrial
      fibrillation in the emergency department.

PMID- 19104109
TI  - Pre-hospital use of ketamine for analgesia and procedural sedation.
AB  - The safe delivery of adequate analgesia and appropriate sedation is a priority in
      prehospital care. The use of ketamine is described for analgesia and sedation in
      1030 trauma patients in a physician-led prehospital trauma service. Ketamine was
      mainly used in awake non-trapped patients with blunt trauma for procedural
      sedation and analgesia. Detailed database searches did not demonstrate loss of
      airway, oxygen desaturation or clinically significant emergence reactions after
      ketamine administration. Ketamine is relatively safe when used by physicians in
      prehospital trauma care.

PMID- 19104110
TI  - Emergency intubation: a prospective multicentre descriptive audit in an
      Australian helicopter emergency medical service.
AB  - OBJECTIVE: To describe the safety profile of emergency airway management when
      performed by a prehospital team consisting of a doctor and a paramedic. Success
      rates, the incidence of difficult airways and the ability of prehospital doctors
      to determine a difficult airway are reported. METHODS: A prospective audit and
      descriptive study of three Australian helicopter emergency medical service (HEMS)
      bases, over a 9-month period. Doctors completed questionnaires regarding the
      number of endotracheal intubation (ETI) attempts on patients transported
      intubated and ventilated, Cormack and Lehane view of the cords during
      laryngoscopy and the anticipated and actual ease of ETI. RESULTS: A total of 114
      (11.4%) patients transported by the HEMS was intubated and ventilated. Study
      questionnaires were completed on 89 of the 114 cases (78.1%), of which 32 (36%)
      were trauma related. HEMS were involved with 43 (48.3%) of the 89 intubations and
      performed 12.4% (n = 11) out of hospital. The HEMS ETI success rate was 97.6%. No
      surgical airways were performed. The actual incidence of difficult airways was
      higher (n = 4, 9.3%) than the anticipated incidence (n = 1, 2.3%). Six patients
      (14.0%) were successfully intubated by the doctor after the paramedic failed.
      CONCLUSIONS: Well-trained doctor paramedic teams, utilising standardised
      operating procedures, can safely perform rapid sequence induction and ETI in the
      prehospital and emergency environment. However, prehospital doctors are not
      always able to anticipate a difficult airway. The complication rate was similar
      to that in hospital emergency departments and to that of other physician-led
      HEMS.

PMID- 19104111
TI  - An unusual cause of chest pain: atraumatic clostridial myonecrosis.
AB  - Atraumatic clostridial myonecrosis is a rare but potentially life-threatening
      infective condition which is thought to occur in elderly and immunocompromised
      subjects via bacterial translocation through the gut wall and distant
      haematological seeding. Previous case reports have mainly focused on an
      association with malignancy and bowel inflammation. The case is reported of an 84
      year-old woman initially treated for cardiac chest pain, with a medical history
      comprising only of type 2 diabetes, hypertension and monoclonal gammopathy of
      unknown significance. Chest pain remains a common presentation to all emergency
      departments worldwide and, with increasing pressure for early intervention in
      cardiac causes, prehospital treatment is becoming more commonplace. Clinicians
      must be sure to make a thorough initial assessment and take care when prescribing
      cardiac medications for chest pain, owing to the vast spectrum of differential
      diagnoses.

PMID- 19104112
TI  - Headache as a sign of phaeochromocytoma.

PMID- 19104113
TI  - Wunderlich's syndrome due to spontaneous rupture of large bilateral
      angiomyolipomas.
AB  - Spontaneous renal haemorrhage, or Wunderlich's syndrome, is an unusual cause of
      acute abdomen. It is a rare disease, usually secondary to tumours, and is an
      emergency and life-threatening condition. CT scanning is highly recommended to
      achieve a definitive diagnosis and to determine the approach to follow, trying to
      use conservative surgery whenever possible, although our case was treated with
      nephrectomy. The case history is reported of spontaneous renal haemorrhage or
      Wunderlich syndrome secondary to bilateral giant renal angiomyolipomas in a 21
      year-old patient with tuberous sclerosis.

PMID- 19104114
TI  - Emergency management of penile strangulation: a case report and review of the
      Chinese literature.
AB  - A 36-year-old Chinese man presented to the emergency department with a steel hoop
      entrapment on his penis for 10 h. The constricting steel hoop was 20 mm in
      external diameter, 18 mm in internal diameter and 15 mm wide. To cut off the
      steel hoop an orthopaedic fret-saw and pinchers were used to make intermittent
      cutting at the opposite side. The total operation time was 100 min. The patient
      was discharged 4 days later with a satisfactory outcome. A review of seven cases
      of penile strangulation reported in the Chinese database of CNKI between 1990 and
      2007 showed that tetanus prophylaxis and pain control did not receive adequate
      attention. A positive correlation was found between the time of incarceration and
      the length of hospitalisation.

PMID- 19104115
TI  - Valsalva retinopathy presenting with subhyaloid haemorrhage.

PMID- 19104117
TI  - Ice/cryotherapy and management of soft tissue injuries.

PMID- 19104118
TI  - Status epilepticus after topical application of a solution containing camphor.

PMID- 19104119
TI  - Ultrasound venous access simulation: the Italian job.

PMID- 19104121
TI  - Internal and external urinary catheters: a primer for clinical practice.
AB  - Internal and external urinary catheters are used to manage urinary incontinence
      and incomplete bladder emptying. Bladder dysfunction cause determines whether
      short- or long-term catheter use is required which, in turn, determines whether
      an indwelling, intermittent, or external catheter should be used. The method of
      catheterization is based on the underlying bladder condition, the goals of
      treatment, and gender appropriateness. Complications such as infection (eg,
      catheter-associated urinary tract infection, sepsis) and its related sequelae
      have been found to be directly related to length of time of catheter use (eg,
      women are at greater risk for catheter-associated urinary tract infection when an
      indwelling catheter is in place >2 weeks); thus, catheter use must be medically
      justified and in the case of an indwelling catheter, involve the shortest period
      possible to ensure patient safety and regulatory compliance. Some newer catheter
      systems include coatings to prevent complications; complications specific to
      indwelling catheter use include obstruction from encrustations, urethral trauma
      and erosion, bladder stones and bladder cancer, and, in men, epididymitis.
      Complications from external catheters may occur when skin condition is
      compromised. Overuse of catheters has reimbursement ramifications. Numerous
      guidelines reflect the need for the judicious use of urinary catheters,
      particularly in long-term care patients. Because evidence-based research on long
      term use of these devices is lacking, clinicians should use clinical experience
      when caring for patients with catheters.

PMID- 19104122
TI  - A blinded, prospective, randomized controlled trial of topical negative pressure
      wound closure in India.
AB  - Wound closure using topical negative pressure (TNP) has been reported to be
      effective, but equipment costs can be prohibitive in resource-challenged
      countries. Because nonhealing wounds are exceedingly common in developing
      countries such as India, the ability to optimize wound care with limited
      resources is very important. To investigate the feasibility and efficacy of
      providing TNP in an Indian medical referral center, a randomized controlled trial
      comparing a locally constructed TNP device (treatment) to wet-to-dry gauze
      dressings (control) was conducted. Eligible study participants (N = 48) were
      recruited from the inpatient wards. Wound etiologies included diabetic foot
      ulcers (15), pressure ulcers (11), cellulitis/fasciitis (11), and "other" (11).
      Following enrollment, wound size was assessed using computer-aided measurements
      of digital photographs and block-randomized to the study arms using a concealed
      allocation table. Wounds in both treatment groups were debrided before dressing
      application and patients were followed until wound closure or being lost to
      follow-up for an average of 26.3 days (+/- 18.5) in the control and 33.1 days (+/
      37.3) in the treatment group. No statistically significant differences in time
      to closure between the two treatment groups were observed except in a subset
      analysis of pressure ulcers (mean 10 +/- 7.11 days for treatment and 27 +/- 10.6
      days in control group, P = 0.05). Direct costs to close a pressure ulcer also
      were lower in the TNP than in the control group. A review of the literature
      suggests the outcomes obtained using a locally constructed TNP device are similar
      to those obtained using commercially available devices. As a result of this
      study, a dedicated tissue viability team has been established to identify wounds
      suitable for TNP, oversee treatment, monitor the need for surgical debridement,
      and employ wound healing principles and technology appropriately. These results
      suggest that inexpensive materials can be utilized for TNP wound closure in a
      developing country.

PMID- 19104123
TI  - Alcaligenes xylosoxidans cholecystitis and meningitis acquired during bathing
      procedures in a burn unit: a case report.
AB  - The information in this article was presented at the 37th Annual Meeting of the
      Japan Society of Burn, Nagoya, Japan, June 7-8, 2008. Alcaligenes xylosoxidans, a
      nonfermentative, Gram-negative rod often found in aqueous environments, has been
      isolated from respirators, incubators, and disinfectant solutions in the hospital
      environment. It is known to cause disease in immunocompromised (eg, burn)
      patients and represents a cross-contamination risk related to wound care. In the
      authors' burn unit, two patients, admitted with deep dermal burns during a 1
      month time period, acquired serious A. xylosoxidans infections. The first
      involved A. xylosoxidans-associated cholecystitis in an adult with 32% total body
      surface area (TBSA) burns and the second involved A. xylosoxidans meningitis in
      an adult with 30% TBSA burns. Both patients received hydrotherapy (bathing) in
      the same bathing tub, one patient after the other. Culture from environmental
      sources isolated A. xylosoxidans from the bathing mattress. Bacterial analysis of
      the isolates, including antimicrobial susceptibility testing and pulsed-field gel
      electrophoresis, suggested the patients had been infected by the same strain -
      ie, cross-contaminated - probably during treatment of their burns. The isolated
      strains were resistant not only to broad-spectrum penicillins and cephalosporins,
      but also to imipenem, to which past A. xylosoxidans strains have been
      susceptible. These findings underscore the need for strict infection control to
      prevent cross-contamination and disease outbreak.

PMID- 19104124
TI  - Acoustic pressure wound therapy to debride unstageable pressure ulcers in the
      acute care setting: a case series.
AB  - As of October 1, 2008, prompt identification and accurate staging of pressure
      ulcers present on admission to acute care hospitals became essential for Medicare
      reimbursement. In short, Medicare will no longer cover the added costs associated
      with care of Stage III and Stage IV pressure ulcers not present on admission;
      such ulcers will be classified as hospital-acquired conditions that could
      reasonably be prevented with application of evidence-based guidelines.
      Unstageable pressure ulcers present a particular challenge under the new policy.
      According to national pressure ulcer guidelines, until enough slough and/or
      eschar is removed to expose the base of the wound, the true depth, and therefore
      stage, cannot be determined. The authors describe the first three patients (a 61
      year-old woman and 52-year-old and 89-year-old men, all with different
      comorbidities and ulcer locations) to receive acoustic pressure wound therapy
      (APWT) for rapid debridement of unstageable pressure ulcers at their acute care
      hospital. Within 2 days, ulcers that had been completely covered with slough
      and/or eschar were cleared enough to be accurately identified as Stage III or
      Stage IV. Rapid and efficient debridement maximized reimbursement potential for
      the additional costs associated with these advanced-stage pressure ulcers.

PMID- 19104125
TI  - Electrophysiology: a subspecialty coming of age in India.

PMID- 19104126
TI  - Non-pharmacological treatment of atrial fibrillation.

PMID- 19104127
TI  - Ventricular fibrillation--current concepts.

PMID- 19104128
TI  - Tachyarrhythmias in infants and children with congenital heart disease.

PMID- 19104129
TI  - Electrophysiology: genesis and prospects.

PMID- 19104130
TI  - Emerging dimensions in electrophysiology.

PMID- 19104131
TI  - Newer mapping technology--when are they really needed?

PMID- 19104132
TI  - Inappropriate ICD therapy--a problem and a challenge.

PMID- 19104133
TI  - Cardiac resynchronization therapy--who benefits? Separating myths from facts.

PMID- 19104134
TI  - Coronary veins and their role in current electrophysiology.

PMID- 19104136
TI  - Differential response of peripheral arterial compliance-related indices to a
      vasoconstrictive stimulus.
AB  - Peripheral arterial elastic properties are greatly affected by cardiovascular as
      well as other pathologies, and their assessment can provide useful diagnostic
      indicators. The photoplethysmographic technique can provide finger blood volume
      and pressure waveforms non-invasively, which can then be processed statically or
      beat-to-beat to characterize parameters of the vessel wall mechanics. We employ
      an occlusion-deflation protocol in 48 healthy volunteers to study peripheral
      artery compliance-related indices over positive and negative transmural pressure
      values as well as under the influence of a valid vasoconstrictor (cigarette
      smoking). We calculate beat-to-beat indices (compliance index CI, distensibility
      index DI, three viscoelastic model parameters (compliance C, viscosity R and
      inertia L), pressure-volume loop areas A and damping factor DF as well as
      symmetrical (C(max)) and asymmetrical (C(A)(max)) static compliance estimates,
      and their distributions over transmural pressure. All distributions are bell
      shaped and centred on negative transmural pressure values. Distribution heights
      were significantly lower in the smoking group (w.r.t. the non-smoking group) for
      C, CI, DI and significantly higher in R and DF. The estimated volume signal time
      lag was also significantly lower in the smoking group. Left and right
      distribution widths were significantly different in all parameters/groups but DI
      (both groups), C(A)(max), A (smoking group) and L (non-smoking group), and
      positions of maxima/minima were significantly altered in C(A)(max), R and DF. C,
      DF and CI are seen to be most sensitive under this protocol, while C(max) and
      C(A)(max) are seen to be insensitive. These quantities provide complementary,
      time- and transmural pressure-dependent information about arterial wall
      mechanics, and the choice of index should depend on the physiological conditions
      at hand as well as relevant time resolution and transmural pressure range.

PMID- 19104135
TI  - Design of a light stimulator for fetal and neonatal magnetoencephalography.
AB  - The design, safety analysis and performance of a fetal visual stimulation system
      suitable for fetal and neonatal magnetoencephalography studies are presented. The
      issue of fetal, neonatal and maternal safety is considered and the maximum
      permissible exposure is computed for the maternal skin and the adult eye. The
      risk for neonatal eye exposure is examined. It is demonstrated that the fetus,
      neonate and mother are not at risk.

PMID- 19104137
TI  - Safety of pulsed electric devices.
AB  - The strength-duration curve for tissue excitation can be modeled by a parallel
      resistor-capacitor circuit that has a time constant. We tested several short
      duration electric generators: five electric fence energizers, the Taser X26 and a
      high-frequency generator to determine their current-versus-time waveforms. We
      estimated their safety characteristics using existing IEC and UL standards for
      electric fence energizers. The current standards are difficult to follow, with
      cumbersome calculations, and do not explicitly explain the physiological
      relevance of the calculated parameters. Hence we propose a new standard. The
      proposed new standard would consist of a physical RC circuit with a certain time
      constant. The investigator would discharge the device into a passive resistor
      capacitor circuit and measure the resulting maximum voltage. If the maximum
      voltage does not exceed a limit, the device passes the test.

PMID- 19104138
TI  - Decoding subjective preference from single-trial near-infrared spectroscopy
      signals.
AB  - Near-infrared spectroscopy (NIRS) has recently been identified as a safe,
      portable and relatively low-cost signal acquisition tool for non-invasive brain
      computer interface (BCI) development. The ultimate goal of BCI research is for
      the user to be able to communicate functional intent directly through thoughts.
      In this paper we propose an NIRS-BCI paradigm based on directly decoding neural
      correlates of decision making, specifically subjective preference evaluation.
      Nine subjects were asked to mentally evaluate two possible drinks and decide
      which they preferred. Frequency domain near-infrared spectroscopy was used to
      image each subject's prefrontal cortex during the task. Using mean signal
      amplitudes as features and linear discriminant analysis, we were able to decode
      which drink was preferred on a single-trial basis with an average accuracy of
      80%.

PMID- 19104139
TI  - Creation of highly aligned electrospun poly-L-lactic acid fibers for nerve
      regeneration applications.
AB  - Aligned, electrospun polymer fibers have shown considerable promise in directing
      regenerating axons in vitro and in vivo. However, in several studies, final
      electrospinning parameters are presented for producing aligned fiber scaffolds,
      and alignment where minimal fiber crossing occurs is not achieved. Highly aligned
      species are necessary for neural tissue engineering applications to ensure that
      axonal extension occurs through a regenerating environment efficiently. Axonal
      outgrowth on fibers that deviate from the natural axis of growth may delay axonal
      extension from one end of a scaffold to the other. Therefore, producing aligned
      fiber scaffolds with little fiber crossing is essential. In this study, the
      contributions of four electrospinning parameters (collection disk rotation speed,
      needle size, needle tip shape and syringe pump flow rate) were investigated
      thoroughly with the goal of finding parameters to obtain highly aligned
      electrospun fibers made from poly-L-lactic acid (PLLA). Using an 8 wt% PLLA
      solution in chloroform, a collection disk rotation speed of 1000 revolutions per
      minute (rpm), a 22 gauge, sharp-tip needle and a syringe pump rate of 2 ml h(-1)
      produced highly aligned fiber (1.2-1.6 microm in diameter) scaffolds verified
      using a fast Fourier transform and a fiber alignment quantification technique.
      Additionally, the application of an insulating sheath around the needle tip
      improved the rate of fiber deposition (electrospinning efficiency). Optimized
      scaffolds were then evaluated in vitro using embryonic stage nine (E9) chick
      dorsal root ganglia (DRGs) and rat Schwann cells (SCs). To demonstrate the
      importance of creating highly aligned scaffolds to direct neurite outgrowth,
      scaffolds were created that contained crossing fibers. Neurites on these
      scaffolds were directed down the axis of the aligned fibers, but neurites also
      grew along the crossed fibers. At times, these crossed fibers even stopped
      further axonal extension. Highly aligned PLLA fibers generated under optimized
      electrospinning conditions guided neurite and SC growth along the aligned fibers.
      Schwann cells demonstrated the bipolar phenotype seen along the fibers. Using a
      novel technique to determine fiber density, an increase in fiber density
      correlated to an increase in the number of neurites, but average neurite length
      was not statistically different between the two different fiber densities.
      Together, this work presents methods by which to produce highly aligned fiber
      scaffolds efficiently and techniques for assessing neurite outgrowth on different
      fiber scaffolds, while suggesting that crossing fibers may be detrimental in
      fostering efficient, directed axonal outgrowth.

PMID- 19104140
TI  - Neurite outgrowth at the interface of 2D and 3D growth environments.
AB  - Growing neurons navigate complex environments, but in vitro systems for studying
      neuronal growth typically limit the cues to flat surfaces or a single type of
      cue, thereby limiting the resulting growth. Here we examined the growth of
      neurons presented with two-dimensional (2D) substrate-bound cues when these cues
      were presented in conjunction with a more complex three-dimensional (3D)
      architecture. Dorsal root ganglia (DRG) explants were cultured at the interface
      between a collagen I matrix and a glass coverslip. Laminin (LN) or chondroitin
      sulfate proteoglycans (CSPG) were uniformly coated on the surface of the glass
      coverslip or patterned in 50 microm tracks by microcontact printing. Quantitative
      analysis of neurite outgrowth with a novel grid system at multiple depths in the
      gel revealed several interesting trends. Most of the neurites extended at the
      surface of the gel when LN was presented whereas more neurites extended into the
      gel when CSPG was presented. Patterning of cues did not affect neurite density or
      depth of growth. However, neurite outgrowth near the surface of the gel aligned
      with LN patterns, and these extensions were significantly longer than neurites
      extended in other cultures. In interface cultures, DRG growth patterns varied
      with the type of cue where neurite density was higher in cultures presenting LN
      than in cultures presenting CSPG. These results represent an important step
      toward understanding how neurons integrate local structural and chemical cues to
      make net growth decisions.

PMID- 19104142
TI  - CD4+ T cells mediate cytotoxicity in neurodegenerative diseases.
AB  - Neuroinflammation, characterized by activated microglia and infiltrating T cells,
      is a prominent pathological feature in neurodegenerative diseases. However,
      whether this inflammation contributes to neuronal injury or is a late consequence
      of neuronal injury is unclear. In this issue of the JCI, Brochard et al. report
      that CD4+ T cells are cytotoxic in a mouse model of Parkinson disease (PD) (see
      the related article beginning on page 182). Specifically, invading T lymphocytes
      contributed to neuronal cell death via the Fas/FasL pathway. The results
      implicate the adaptive immune system in the pathogenesis of Parkinson
      neurodegeneration and provide a meaningful rationale for immune-based therapies
      for PD.

PMID- 19104141
TI  - Neuron network activity scales exponentially with synapse density.
AB  - Neuronal network output in the cortex as a function of synapse density during
      development has not been explicitly determined. Synaptic scaling in cortical
      brain networks seems to alter excitatory and inhibitory synaptic inputs to
      produce a representative rate of synaptic output. Here, we cultured rat
      hippocampal neurons over a three-week period to correlate synapse density with
      the increase in spontaneous spiking activity. We followed the network development
      as synapse formation and spike rate in two serum-free media optimized for either
      (a) neuron survival (Neurobasal/B27) or (b) spike rate (NbActiv4). We found that
      while synaptophysin synapse density increased linearly with development, spike
      rates increased exponentially in developing neuronal networks. Synaptic receptor
      components NR1, GluR1 and GABA-A also increase linearly but with more excitatory
      receptors than inhibitory. These results suggest that the brain's information
      processing capability gains more from increasing connectivity of the processing
      units than increasing processing units, much as Internet information flow
      increases much faster than the linear number of nodes and connections.

PMID- 19104143
TI  - Role for alpha3 integrin in EMT and pulmonary fibrosis.
AB  - Idiopathic pulmonary fibrosis (IPF) is characterized by progressive
      (myo)fibroblast accumulation and collagen deposition. One possible source of
      (myo)fibroblasts is epithelial cells that undergo epithelial-mesenchymal
      transition (EMT), a process frequently mediated by TGF-beta. In this issue of the
      JCI, Kim et al. report that epithelial cell-specific deletion of alpha3 integrin
      prevents EMT in mice, thereby protecting against bleomycin-induced fibrosis (see
      the related article beginning on page 213). The authors propose a novel mechanism
      linking TGF-beta and beta-catenin signaling in EMT through integrin-dependent
      association of tyrosine-phosphorylated beta-catenin and pSmad2 and suggest
      targeted disruption of this interaction as a potential therapeutic approach.

PMID- 19104144
TI  - Predicting response to hepatitis C therapy.
AB  - Current treatment for chronic hepatitis C is expensive, is often accompanied by
      burdensome side effects, and, sadly, fails in almost half of cases. The ability
      to predict such failures prior to treatment could save a great deal of pain and
      expense for the patient with HCV. In this issue of the JCI, Aurora and colleagues
      describe the development of genetic markers predictive of treatment response
      based on a study of viral sequence variation (see the related article beginning
      on page 225). Genome-wide covariation analyses of pretreatment virus sequences
      from 94 patients showed distinct patterns of mutations strongly associated with
      the ultimate success or failure of treatment. Such analyses suggest markers
      predictive of response to therapy and may lead to new insights into the
      underlying biology of hepatitis C.

PMID- 19104145
TI  - Deciphering migraine.
AB  - Migraine is an episodic headache disorder affecting as many as 10% of people
      worldwide. Familial hemiplegic migraine (FHM) is an autosomal dominant subtype of
      severe migraine accompanied by visual disturbances known as aura. Migrainous aura
      is caused by cortical spreading depression (CSD) - a slowly advancing wave of
      tissue depolarization in the cortex. More than half of FHM cases are caused by
      mutations in the CACNA1A gene, which encodes a neuronal Cav2.1 Ca2+ channel,
      resulting in increased Ca2+ flow into dendrites and excessive release of the
      excitatory neurotransmitter glutamate. In this issue of the JCI, Eikermann
      Haerter et al. show that transgenic mice with FHM-associated mutations in Cacna1a
      have increased susceptibility to CSD compared with wild-type animals, likely due
      to augmentation of excitatory neurotransmission (see the related article
      beginning on page 99). Additional as-yet-undefined channel mutations may
      similarly render the migraine brain more susceptible to the initiation of CSD,
      with implications not only for the genesis of migraine but also for the hypoxic
      injury that accompanies its worst manifestation, complicated migraine.

PMID- 19104146
TI  - Revisiting Notch in remyelination of multiple sclerosis lesions.
AB  - MS results from destruction of the protective myelin sheath surrounding axons,
      which prevents the transmission of nerve impulses. Precursors of
      oligodendrocytes, the cells capable of myelinating axons, are preserved in
      demyelinating lesions; however, why these precursors do not differentiate into
      mature oligodendrocytes and remyelinate axons is unknown. Contactin is a
      noncanonical Notch receptor ligand that mediates oligodendrocyte differentiation.
      In this issue of the JCI, Nakahara et al. show that Contactin is abundantly
      expressed on demyelinated axons in human chronic MS lesions and that Notch1 is
      activated in oligodendrocyte precursor cells (see the related article beginning
      on page 169). However, Notch1 intracellular domain coassociates with the nuclear
      transporter Importin beta but fails to show evidence of nuclear translocation.
      These cytoplasmic aggregates also contain TAT-interacting protein 30 kDa (TIP30),
      a proapoptotic factor, which inhibits nuclear transport and, consequently, Notch1
      mediated oligodendrocyte differentiation and remyelination. These data target
      TIP30 as a new pathogenic factor in MS.

PMID- 19104147
TI  - Genome-wide hepatitis C virus amino acid covariance networks can predict response
      to antiviral therapy in humans.
AB  - Hepatitis C virus (HCV) is a common RNA virus that causes hepatitis and liver
      cancer. Infection is treated with IFN-alpha and ribavirin, but this expensive and
      physically demanding therapy fails in half of patients. The genomic sequences of
      independent HCV isolates differ by approximately 10%, but the effects of this
      variation on the response to therapy are unknown. To address this question, we
      analyzed amino acid covariance within the full viral coding region of pretherapy
      HCV sequences from 94 participants in the Viral Resistance to Antiviral Therapy
      of Chronic Hepatitis C (Virahep-C) clinical study. Covarying positions were
      common and linked together into networks that differed by response to therapy.
      There were 3-fold more hydrophobic amino acid pairs in HCV from nonresponding
      patients, and these hydrophobic interactions were predicted to contribute to
      failure of therapy by stabilizing viral protein complexes. Using our analysis to
      detect patterns within the networks, we could predict the outcome of therapy with
      greater than 95% coverage and 100% accuracy, raising the possibility of a
      prognostic test to reduce therapeutic failures. Furthermore, the hub positions in
      the networks are attractive antiviral targets because of their genetic linkage
      with many other positions that we predict would suppress evolution of resistant
      variants. Finally, covariance network analysis could be applicable to any virus
      with sufficient genetic variation, including most human RNA viruses.

PMID- 19104148
TI  - Epithelial cell alpha3beta1 integrin links beta-catenin and Smad signaling to
      promote myofibroblast formation and pulmonary fibrosis.
AB  - Pulmonary fibrosis, in particular idiopathic pulmonary fibrosis (IPF), results
      from aberrant wound healing and scarification. One population of fibroblasts
      involved in the fibrotic process is thought to originate from lung epithelial
      cells via epithelial-mesenchymal transition (EMT). Indeed, alveolar epithelial
      cells (AECs) undergo EMT in vivo during experimental fibrosis and ex vivo in
      response to TGF-beta1. As the ECM critically regulates AEC responses to TGF
      beta1, we explored the role of the prominent epithelial integrin alpha3beta1 in
      experimental fibrosis by generating mice with lung epithelial cell-specific loss
      of alpha3 integrin expression. These mice had a normal acute response to
      bleomycin injury, but they exhibited markedly decreased accumulation of lung
      myofibroblasts and type I collagen and did not progress to fibrosis. Signaling
      through beta-catenin has been implicated in EMT; we found that in primary AECs,
      alpha3 integrin was required for beta-catenin phosphorylation at tyrosine residue
      654 (Y654), formation of the pY654-beta-catenin/pSmad2 complex, and initiation of
      EMT, both in vitro and in vivo during the fibrotic phase following bleomycin
      injury. Finally, analysis of lung tissue from IPF patients revealed the presence
      of pY654-beta-catenin/pSmad2 complexes and showed accumulation of pY654-beta
      catenin in myofibroblasts. These findings demonstrate epithelial integrin
      dependent profibrotic crosstalk between beta-catenin and Smad signaling and
      support the hypothesis that EMT is an important contributor to pathologic
      fibrosis.

PMID- 19104149
TI  - Infiltration of CD4+ lymphocytes into the brain contributes to neurodegeneration
      in a mouse model of Parkinson disease.
AB  - Parkinson disease (PD) is a neurodegenerative disorder characterized by a loss of
      dopamine-containing neurons. Mounting evidence suggests that dopaminergic cell
      death is influenced by the innate immune system. However, the pathogenic role of
      the adaptive immune system in PD remains enigmatic. Here we showed that CD8+ and
      CD4+ T cells but not B cells had invaded the brain in both postmortem human PD
      specimens and in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) mouse
      model of PD during the course of neuronal degeneration. We further demonstrated
      that MPTP-induced dopaminergic cell death was markedly attenuated in the absence
      of mature T lymphocytes in 2 different immunodeficient mouse strains (Rag1-/- and
      Tcrb-/- mice). Importantly, similar attenuation of MPTP-induced dopaminergic cell
      death was seen in mice lacking CD4 as well as in Rag1-/- mice reconstituted with
      FasL-deficient splenocytes. However, mice lacking CD8 and Rag1-/- mice
      reconstituted with IFN-gamma-deficient splenocytes were not protected. These data
      indicate that T cell-mediated dopaminergic toxicity is almost exclusively
      arbitrated by CD4+ T cells and requires the expression of FasL but not IFNgamma.
      Further, our data may provide a rationale for targeting the adaptive arm of the
      immune system as a therapeutic strategy in PD.

PMID- 19104152
TI  - Atg4B(C74A) hampers autophagosome closure: a useful protein for inhibiting
      autophagy.
AB  - Recently we have reported that overexpression of an inactive mutant of Atg4B, a
      protease that processes pro-LC3 paralogues, inhibits lipidation of LC3 paralogues
      and autophagic degradation in mammalian cell. Through a mechanistic analysis, it
      was revealed that excess Atg4B mutant sequesters LC3 paralogues and blocks
      formation of Atg7-LC3 intermediate. Upon trap of LC3 paralogues, Atg5-positive
      autophagic structures accumulated. The structures are defective in the final
      closing step in autophagosome formation. The ability of the excess Atg4B mutant
      to inhibit autophagy provides not only an opportunity for further analysis of the
      LC3 system but also a useful tool available for a wide variety of experimental
      systems used in the study of autophagy.

PMID- 19104150
TI  - Genetic and hormonal factors modulate spreading depression and transient
      hemiparesis in mouse models of familial hemiplegic migraine type 1.
AB  - Familial hemiplegic migraine type 1 (FHM1) is an autosomal dominant subtype of
      migraine with aura that is associated with hemiparesis. As with other types of
      migraine, it affects women more frequently than men. FHM1 is caused by mutations
      in the CACNA1A gene, which encodes the alpha1A subunit of Cav2.1 channels; the
      R192Q mutation in CACNA1A causes a mild form of FHM1, whereas the S218L mutation
      causes a severe, often lethal phenotype. Spreading depression (SD), a slowly
      propagating neuronal and glial cell depolarization that leads to depression of
      neuronal activity, is the most likely cause of migraine aura. Here, we have shown
      that transgenic mice expressing R192Q or S218L FHM1 mutations have increased SD
      frequency and propagation speed; enhanced corticostriatal propagation; and,
      similar to the human FHM1 phenotype, more severe and prolonged post-SD
      neurological deficits. The susceptibility to SD and neurological deficits is
      affected by allele dosage and is higher in S218L than R192Q mutants. Further,
      female S218L and R192Q mutant mice were more susceptible to SD and neurological
      deficits than males. This sex difference was abrogated by ovariectomy and
      senescence and was partially restored by estrogen replacement, implicating
      ovarian hormones in the observed sex differences in humans with FHM1. These
      findings demonstrate that genetic and hormonal factors modulate susceptibility to
      SD and neurological deficits in FHM1 mutant mice, providing a potential mechanism
      for the phenotypic diversity of human migraine and aura.

PMID- 19104158
TI  - Anesthetic effects on the developing brain: insights from epidemiology.

PMID- 19104151
TI  - Abnormal expression of TIP30 and arrested nucleocytoplasmic transport within
      oligodendrocyte precursor cells in multiple sclerosis.
AB  - Oligodendrocyte precursor cells (OPCs) persist near the demyelinated axons
      arising in MS but inefficiently differentiate into oligodendrocytes and
      remyelinate these axons. The pathogenesis of differentiation failure remains
      elusive. We initially hypothesized that injured axons fail to present Contactin,
      a positive ligand for the oligodendroglial Notch1 receptor to induce myelination,
      and thus tracked axoglial Contactin/Notch1 signaling in situ, using
      immunohistochemistry in brain tissue from MS patients containing chronic
      demyelinated lesions. Instead, we found that Contactin was saturated on
      demyelinated axons, Notch1-positive OPCs accumulated in Contactin-positive
      lesions, and the receptor was engaged, as demonstrated by cleavage to Notch1
      intracellular domain (NICD). However, nuclear translocalization of NICD, required
      for myelinogenesis, was virtually absent in these cells. NICD and related
      proteins carrying nuclear localization signals were associated with the nuclear
      transporter Importin but were trapped in the cytoplasm. Abnormal expression of
      TIP30, a direct inhibitor of Importin, was observed in these OPCs. Overexpression
      of TIP30 in a rat OPC cell line resulted in cytoplasmic entrapment of NICD and
      arrest of differentiation upon stimulation with Contactin-Fc. Our results suggest
      that extracellular inhibitory factors as well as an intrinsic nucleocytoplasmic
      transport blockade within OPCs may be involved in the pathogenesis of
      remyelination failure in MS.

PMID- 19104159
TI  - In search of excellence in anesthesiology.

PMID- 19104160
TI  - Laryngoscopy force, visualization, and intubation failure in acute trauma: should
      we modify the practice of manual in-line stabilization?

PMID- 19104161
TI  - Why obstetric anesthesiologists get sued.

PMID- 19104163
TI  - Filling in the blanks.

PMID- 19104164
TI  - America's first patented series of bubble-through anesthetic vaporizers: Reverend
      Samuel J. Hayes' sermons against asphyxial anesthesia.

PMID- 19104165
TI  - Practice alert for the perioperative management of patients with coronary artery
      stents: a report by the American Society of Anesthesiologists Committee on
      Standards and Practice Parameters.

PMID- 19104166
TI  - Manual in-line stabilization increases pressures applied by the laryngoscope
      blade during direct laryngoscopy and orotracheal intubation.
AB  - BACKGROUND: Manual in-line stabilization (MILS) is recommended during direct
      laryngoscopy and intubation in patients with known or suspected cervical spine
      instability. Because MILS impairs glottic visualization, the authors hypothesized
      that anesthesiologists would apply greater pressure during intubations with MILS
      than without. METHODS: Nine anesthetized and pharmacologically paralyzed patients
      underwent two sequential laryngoscopies and intubations, one with MILS and one
      without, in random order. A transducer array along a Macintosh 3 laryngoscope
      blade continuously measured applied pressures, and glottic view was
      characterized. RESULTS: With MILS, glottic visualization was worse in six
      patients, and intubation failure occurred in two of these six patients. Maximum
      laryngoscope pressure at best glottic view was greater with MILS than without
      (717 +/- 339 mmHg vs. 363 +/- 121 mmHg, respectively; n = 8; P = 0.023). Other
      measures of pressure application also indicated comparable increases with MILS.
      CONCLUSION: Pressures applied to airway tissues by the laryngoscope blade are
      secondarily transmitted to the cervical spine and result in cranio-cervical
      motion. In the presence of cervical instability, impaired glottic visualization
      and secondary increases in pressure application with MILS have the potential to
      increase pathologic cranio-cervical motion.

PMID- 19104167
TI  - Laryngoscopy via Macintosh blade versus GlideScope: success rate and time for
      endotracheal intubation in untrained medical personnel.
AB  - BACKGROUND: Tracheal intubation is the preferred technique to secure the airway
      and apply mechanical ventilation. However, when performed by untrained medical
      personnel, tracheal intubation via direct laryngoscopy has a high rate of
      failure. The GlideScope (Verathon Medical Europe, Ijsselstein, Netherlands)
      technique improves the success rate for difficult tracheal intubation performed
      by experienced physicians; whether this technique improves the success rate for
      normal intubations when performed by inexperienced personnel as well is unknown.
      Therefore, the authors compared the success rate of direct laryngoscopy versus
      the GlideScope technique performed by personnel inexperienced in tracheal
      intubations. METHODS: Twenty volunteers, who had had only manikin training for
      tracheal intubation, attempted 5 intubations with either technique in patients
      scheduled for general anesthesia within a time limit of 120 s. RESULTS: Two
      hundred patients were divided into 2 groups for intubation via direct
      laryngoscopy (n = 100) or the GlideScope technique (n = 100). Between groups,
      there was neither a clinically relevant difference in the anthropometric data nor
      in the medication used for anesthesia. The overall success rate was 93% for the
      GlideScope technique versus 51% for direct laryngoscopy (P < 0.01). Time for
      intubation was 89 +/- 35 s for direct laryngoscopy versus 63 +/- 30 s for
      GlideScope technique (P < 0.01). CONCLUSION: Tracheal intubation is the preferred
      technique to secure the airways in patients with a high risk of aspiration and is
      important in emergency medicine. Direct laryngoscopy with the Macintosh blade has
      a success rate of only 51% in our subjects. Using the GlideScope technique, a
      success rate of more than 90% within 120 s can be achieved after the first
      attempt, even in personnel untrained in intubation.

PMID- 19104168
TI  - Rigid laryngoscope-assisted insertion of transesophageal echocardiography probe
      reduces oropharyngeal mucosal injury in anesthetized patients.
AB  - BACKGROUND: Intraoperative transesophageal echocardiography has become a routine
      part of monitoring in patients with cardiac disease. However, insertion of a
      transesophageal echocardiography probe can be associated with oropharyngeal,
      esophageal, and gastric injuries. The purpose of this study was to determine
      whether insertion of a transesophageal echocardiography probe under direct
      laryngoscopic visualization can reduce the incidence of oropharyngeal mucosal
      injury. METHODS: Eighty patients undergoing surgery with general anesthesia were
      randomly allocated to either the conventional group, in which the probe was
      inserted blindly, or the laryngoscope group, in which a rigid laryngoscope was
      used to visualize the passage of the probe. The incidence of oropharyngeal
      mucosal injury, the number of insertion attempts, and odynophagia were assessed.
      RESULTS: There was no significant difference in demographic and hemodynamic
      parameters between the 2 groups. The incidence of oropharyngeal mucosal injury
      was higher in the conventional group than in the laryngoscope group (55% vs. 5%,
      P < 0.05). The incidence of odynophagia was higher in the conventional group than
      in the laryngoscope group (32.5% vs. 2.5%, P < 0.05). The number of insertion
      attempts was also higher in the conventional group than in the laryngoscope
      group. CONCLUSION: Rigid laryngoscope-assisted insertion of the transesophageal
      echocardiography probe reduces the incidence of oropharyngeal mucosal injury,
      odynophagia, and the number of insertion attempts.

PMID- 19104169
TI  - Respiratory and sleep effects of remifentanil in volunteers with moderate
      obstructive sleep apnea.
AB  - BACKGROUND: There is concern that opioid-based analgesia will worsen sleep
      related respiratory insufficiency in patients with obstructive sleep apnea (OSA),
      resulting in serious morbidity or mortality. However, there are no studies that
      directly address the merit of this concern. Consequently, the authors designed
      this study as the first prospective, double-blind, placebo-controlled
      investigation of opioid pharmacology in patients with documented OSA. METHODS:
      Patients (n = 19) with moderate OSA documented by polysomnography (sleep study)
      were randomized to undergo an additional sleep study while receiving either a
      saline infusion or a remifentanil infusion (0.075 microg x kg x h). Sleep stages,
      apneas, hypopneas, and arterial hemoglobin oxygen saturation were continually
      recorded during saline or remifentanil infusion, and were compared with values
      obtained during the patients' earlier sleep study. RESULTS: Saline infusion had
      no effect on sleep or respiratory variables. In contrast, remifentanil increased
      Stage 1 sleep, markedly decreased rapid eye movement sleep, increased arousals
      from sleep, and decreased sleep efficiency. Remifentanil actually decreased the
      number of obstructive apneas, but markedly increased the number of central
      apneas. Arterial hemoglobin oxygen saturation was also significantly lower in OSA
      patients receiving remifentanil. CONCLUSIONS: The decrease in obstructive apneas
      likely resulted from the marked decrease in rapid eye movement sleep caused by
      remifentanil. Despite fewer obstructions, OSA was worse during remifentanil
      infusion because of a marked increase in the number of central apneas. These data
      suggest that caution is warranted when administering opioids to subjects with
      moderate OSA, but that the primary risk may be central apnea, not obstructive
      apnea.

PMID- 19104170
TI  - Differential effects of propofol and sevoflurane on ischemia-induced ventricular
      arrhythmias and phosphorylated connexin 43 protein in rats.
AB  - BACKGROUND: The effects of anesthetics on ischemia-induced ventricular
      arrhythmias remain poorly studied. This study investigated the effects of
      propofol and sevoflurane on the survival rate and morbidity as a result of
      ventricular arrhythmias, and defined a possible mechanism for the arrhythmogenic
      properties of anesthetics during acute myocardial ischemia. METHODS: Under
      anesthesia with intraperitoneal sodium pentobarbital, Sprague-Dawley rats
      underwent 30 min of left anterior descending coronary artery ligation. The rats
      were divided into a low-dose propofol (Prop-LD) group (39 mg X kg(-1) X hr(-1), n
      = 18), a high-dose propofol group (78 mg x kg(-1) x hr(-1), n = 18), a
      sevoflurane group (2.5%, n = 18) and a control group (n = 18). The survival rate
      and morbidity as a result of ventricular arrhythmias were determined, and the
      amount of phosphorylated connexin 43 protein was measured 30 min after coronary
      artery ligation. RESULTS: The survival rate was 83% (15 of 18), 94% (17 of 18),
      89% (16 of 18), and 67% (12 of 18, P = 0.038 vs. Prop-LD) in the control, Prop
      LD, high-dose propofol, and sevoflurane groups, respectively. Sustained
      ventricular tachycardia was observed in 83% (15 of 18), 39% (7 of 18, P = 0.011
      vs. control), 50% (9 of 18, P = 0.039 vs. control) and 94% (17 of 18, P < 0.01
      vs. Prop-LD) in the control, Prop-LD, high-dose propofol, and sevoflurane groups,
      respectively. Immunoblotting showed a marked reduction in the amount of
      phosphorylated connexin 43 in the control and sevoflurane groups, as compared
      with the Prop-LD and high-dose propofol groups (P < 0.05). CONCLUSION: The
      authors' results suggest that propofol preserves connexin 43 phosphorylation
      during acute myocardial ischemia, as compared with sevoflurane, and this might
      protect the heart from serious ventricular arrhythmias during acute coronary
      occlusion.

PMID- 19104171
TI  - Preoperative and intraoperative predictors of cardiac adverse events after
      general, vascular, and urological surgery.
AB  - BACKGROUND: The authors sought to determine the incidence and risk factors for
      perioperative cardiac adverse events (CAEs) after noncardiac surgery using
      detailed preoperative and intraoperative hemodynamic data. METHODS: The authors
      conducted a prospective observational study at a single university hospital from
      2002 to 2006. All American College of Surgeons-National Surgical Quality
      Improvement Program patients undergoing general, vascular, and urological surgery
      were included. The CAE outcome definition included cardiac arrest, non-ST
      elevation myocardial infarction, Q-wave myocardial infarction, and new clinically
      significant cardiac dysrhythmia within the first 30 postoperative days. RESULTS:
      Four years of data demonstrated that of 7,740 noncardiac operations, 83 patients
      (1.1%) experienced a CAE within 30 days. Nine independent predictors were
      identified (P < or = 0.05): age > or = 68, body mass index > or = 30, emergent
      surgery, previous coronary intervention or cardiac surgery, active congestive
      heart failure, cerebrovascular disease, hypertension, operative duration > or =
      3.8 h, and the administration of 1 or more units of packed red blood cells
      intraoperatively. The c-statistic of this model was 0.81 +/- 0.02. Univariate
      analysis demonstrated that high-risk patients experiencing a CAE were more likely
      to experience an episode of mean arterial pressure < 50 mmHg (6% vs. 24%, P =
      0.02), experience an episode of 40% decrease in mean arterial pressure (26% vs.
      53%, P = 0.01), and an episode of heart rate > 100 (22% vs. 34%, P = 0.05).
      CONCLUSIONS: In comparison with current risk stratification indices, the
      inclusion of intraoperative elements improves the ability to predict a
      perioperative CAE after noncardiac surgery.

PMID- 19104172
TI  - Preoperative use of statins is associated with reduced early delirium rates after
      cardiac surgery.
AB  - BACKGROUND: Delirium is an acute deterioration of brain function characterized by
      fluctuating consciousness and an inability to maintain attention. Use of statins
      has been shown to decrease morbidity and mortality after major surgical
      procedures. The objective of this study was to determine an association between
      preoperative administration of statins and postoperative delirium in a large
      prospective cohort of patients undergoing cardiac surgery with cardiopulmonary
      bypass. METHODS: After Institutional Review Board approval, data were
      prospectively collected on consecutive patients undergoing cardiac surgery with
      cardiopulmonary bypass from April 2005 to June 2006 in an academic hospital. All
      patients were screened for delirium during their hospitalization using the
      Confusion Assessment Method in the intensive care unit. Multivariable logistic
      regression analysis was used to identify independent perioperative predictors of
      delirium after cardiac surgery. Statins were tested for a potential protective
      effect. RESULTS: Of the 1,059 patients analyzed, 122 patients (11.5%) had
      delirium at any time during their cardiovascular intensive care unit stay.
      Administration of statins had a protective effect, reducing the odds of delirium
      by 46%. Independent predictors of postoperative delirium included older age,
      preoperative depression, preoperative renal dysfunction, complex cardiac surgery,
      perioperative intraaortic balloon pump support, and massive blood transfusion.
      The model was reliable (Hosmer-Lemeshow test, P = 0.3) and discriminative (area
      under receiver operating characteristic curve = 0.77). CONCLUSIONS: Preoperative
      administration of statins is associated with the reduced risk of postoperative
      delirium after cardiac surgery with cardiopulmonary bypass.

PMID- 19104173
TI  - Effects of propofol on cyclic strain-induced endothelin-1 expression in human
      umbilical vein endothelial cells.
AB  - BACKGROUND: Propofol is one of the most popular intravenous induction agents of
      general anesthesia. Experimental results revealed that propofol exerted
      hypotensive and antioxidative effects. However, the intracellular mechanism of
      propofol remains to be delineated. The aims of this study were to test the
      hypothesis that propofol may alter strain-induced endothelin-1 (ET-1) secretion
      and nitric oxide production, and to identify the putative underlying signaling
      pathways in human umbilical vein endothelial cells. METHODS: Cultured human
      umbilical vein endothelial cells were exposed to cyclic strain in the presence of
      propofol, and ET-1 expression was examined by Northern blotting and enzyme-linked
      immunosorbent assay kit. Activation of extracellular signal-regulated protein
      kinase, endothelial nitric oxide synthase, and protein kinase B were assessed by
      Western blot analysis. RESULTS: The authors show that propofol inhibits strain
      induced ET-1 expression, strain-increased reactive oxygen species formation, and
      extracellular signal-regulated protein kinase phosphorylation. On the contrary,
      nitric oxide production, endothelial nitric oxide synthase activity, and protein
      kinase B phosphorylation were enhanced by propofol treatment. Furthermore, in the
      presence of PTIO, a nitric oxide scavenger, and KT5823, a specific inhibitor of
      cyclic guanosine monophosphate-dependent protein kinase, the inhibitory effect of
      propofol on strain-induced extracellular signal-regulated protein kinase
      phosphorylation and ET-1 release was reversed. CONCLUSIONS: The authors
      demonstrate for the first time that propofol inhibits strain-induced ET-1
      secretion and enhances strain-increased nitric oxide production in human
      umbilical vein endothelial cells. Thus, this study delivers important new insight
      into the molecular pathways that may contribute to the proposed hypotensive
      effects of propofol in the cardiovascular system.

PMID- 19104174
TI  - Glucose infusion suppresses surgery-induced muscle protein breakdown by
      inhibiting ubiquitin-proteasome pathway in rats.
AB  - BACKGROUND: It appears to have been well established that after surgery, protein
      catabolism is accelerated and glucose infusion suppresses the catabolic
      reactions. However, in the early postoperative period, the effects of surgical
      stress and glucose infusion on muscle protein catabolism and the related
      mechanisms remain unclear. METHODS: Rats undergoing laparotomy were infused with
      acetated Ringer's solution (10 ml x kg(-1) x h(-1)) without glucose (control) or
      containing 1% or 5% glucose. The infusion was continued for a further 4 h after
      the surgical treatment. The catabolic index, excretion of urinary nitrogen and 3
      methylhistidine, and release of tyrosine and 3-methylhistidine from isolated
      muscle were determined. Furthermore, muscular mRNA expression of proteolytic
      related genes (atrogin-1/MAFbx, muscle ring finger-1, mu- and m-calpain, and
      cathepsin L and H) and phosphorylation of components of insulin signaling
      (forkhead box O3 and protein kinase B) were evaluated. RESULTS: Surgery increased
      the catabolic index, and this increase was suppressed by glucose infusion (both
      1% and 5%). In the control group, mRNA expression of atrogin-1/MAFbx and muscle
      ring finger-1 was increased, and they were suppressed in the two glucose groups.
      Furthermore, insulin signaling (phosphorylation of protein kinase B and forkhead
      box O3) in muscles was stimulated by glucose infusion. CONCLUSION: The present
      study indicates that glucose infusion, even at a relatively low rate, suppresses
      muscle protein breakdown in the early postoperative period. The mechanism of this
      effect is related to the suppression of the ubiquitin-proteasome pathway,
      accompanied by activation of insulin signaling.

PMID- 19104175
TI  - Trends and outcomes of malignant hyperthermia in the United States, 2000 to 2005.
AB  - BACKGROUND: Malignant hyperthermia (MH) is a potentially fatal pharmacogenetic
      disorder with an estimated mortality of less than 5%. The purpose of this study
      was to evaluate the current incidence of MH and the predictors associated with in
      hospital mortality in the United States. METHODS: The Nationwide Inpatient
      Sample, which is the largest all-payer inpatient database in the United States,
      was used to identify patients discharged with a diagnosis of MH during the years
      2000-2005. The weighted exact Cochrane-Armitage test and multivariate logistic
      regression analyses were used to assess trends in the incidence and risk-adjusted
      mortality from MH, taking into account the complex survey design. RESULTS: From
      2000 to 2005, the number of cases of MH increased from 372 to 521 per year. The
      occurrence of MH increased from 10.2 to 13.3 patients per million hospital
      discharges (P = 0.001). Mortality rates from MH ranged from 6.5% in 2005 to 16.9%
      in 2001 (P < 0.0001). The median age of patients with MH was 39 (interquartile
      range, 23-54 yr). Only 17.8% of the patients were children, who had lower
      mortality than adults (0.7% vs. 14.1%, P < 0.0001). Logistic regression analyses
      revealed that risk-adjusted in-hospital mortality was associated with increasing
      age, female sex, comorbidity burden, source of admission to hospital, and
      geographic region of the United States. CONCLUSIONS: The incidence of MH in the
      United States has increased in recent years. The in-hospital mortality from MH
      remains elevated and higher than previously reported. The results of this study
      should enable the identification of areas requiring increased focus in MH-related
      education.

PMID- 19104176
TI  - Pharmacokinetic-pharmacodynamic model for the reversal of neuromuscular blockade
      by sugammadex.
AB  - BACKGROUND: Sugammadex selectively binds steroidal neuromuscular blocking drugs,
      leading to reversal of neuromuscular blockade. The authors developed a
      pharmacokinetic-pharmacodynamic model for reversal of neuromuscular blockade by
      sugammadex, assuming that reversal results from a decrease of free drug in plasma
      and/or neuromuscular junction. The model was applied for predicting the
      interaction between sugammadex and rocuronium or vecuronium. METHODS:
      Noninstantaneous equilibrium of rocuronium-sugammadex complex formation was
      assumed in the pharmacokinetic-pharmacodynamic interaction model. The
      pharmacokinetic parameters for the complex and sugammadex alone were assumed to
      be identical. After development of a pharmacokinetic-pharmacodynamic model for
      rocuronium alone, the interaction model was optimized using rocuronium and
      sugammadex concentration data after administration of 0.1-8 mg/kg sugammadex 3
      min after administration of 0.6 mg/kg rocuronium. Subsequently, the predicted
      reversal of neuromuscular blockade by sugammadex was compared with data after
      administration of up to 8 mg/kg sugammadex at reappearance of second twitch of
      the train-of-four; or 3, 5, or 15 min after administration of 0.6 mg/kg
      rocuronium. Finally, the model was applied to predict reversal of vecuronium
      induced neuromuscular blockade. RESULTS: Using the in vitro dissociation
      constants for the binding of rocuronium and vecuronium to sugammadex, the
      pharmacokinetic-pharmacodynamic interaction model adequately predicted the
      increase in total rocuronium and vecuronium plasma concentrations and the time
      course of reversal of neuromuscular blockade. CONCLUSIONS: Model-based evaluation
      supports the hypothesis that reversal of rocuronium- and vecuronium-induced
      neuromuscular blockade by sugammadex results from a decrease in the free
      rocuronium and vecuronium concentration in plasma and neuromuscular junction. The
      model is useful for prediction of reversal of rocuronium and vecuronium-induced
      neuromuscular blockade with sugammadex.

PMID- 19104177
TI  - Midazolam inhibits tumor necrosis factor-alpha-induced endothelial activation:
      involvement of the peripheral benzodiazepine receptor.
AB  - BACKGROUND: Midazolam is widely used as an intravenous sedative. However, the
      role of midazolam on vascular endothelial activation is still unknown. The
      present study explores the action of midazolam on endothelial activation and its
      role to peripheral benzodiazepine receptor (PBR) in cultured human umbilical vein
      endothelial cells. METHODS: Intracellular localization of PBR in human umbilical
      vein endothelial cells was visualized with immunofluorescent staining. Monocyte
      adhesion and vascular cell adhesion molecule-1 expression were measured with
      monocyte adhesion assay and Western blot analysis. Involvement of PBR was
      assessed by using specific antagonists and small interfering RNA against PBR.
      RESULTS: PBR was localized in the mitochondria of human umbilical vein
      endothelial cells. Midazolam significantly inhibited tumor necrosis factor-alpha
      induced vascular cell adhesion molecule-1 and monocyte adhesion in a dose
      dependent manner (1-30 microM). The midazolam-mediated suppression on the tumor
      necrosis factor-alpha-induced vascular cell adhesion molecule-1 expression and
      monocyte adhesion were inhibited by the pretreatment of PK11195 and not inhibited
      by the flumazenil. Transfection of small interfering RNA for PBR decreased the
      expression of PBR (18 kDa) in human umbilical vein endothelial cells. Midazolam
      mediated suppression on the tumor necrosis factor-alpha-induced vascular cell
      adhesion molecule-1 expression was abrogated by the transfection of small
      interfering RNA for PBR. CONCLUSION: These results suggest that midazolam has an
      inhibitory action on the endothelial activation and that its action is related to
      the activation of peripheral benzodiazepine receptor localized in mitochondria of
      the endothelial cells.

PMID- 19104178
TI  - Prevention of the pulmonary vasoconstrictor effects of HBOC-201 in awake lambs by
      continuously breathing nitric oxide.
AB  - BACKGROUND: Hemoglobin-based oxygen-carrying solutions (HBOC) provide emergency
      alternatives to blood transfusion to carry oxygen to tissues without the risks of
      disease transmission or transfusion reaction. Two primary concerns hampering the
      clinical acceptance of acellular HBOC are the occurrence of systemic and
      pulmonary vasoconstriction and the maintenance of the heme-iron in the reduced
      state (Fe2+). We recently demonstrated that pretreatment with inhaled nitric
      oxide prevents the systemic hypertension induced by HBOC-201 (polymerized bovine
      hemoglobin) infusion in awake mice and sheep without causing methemoglobinemia.
      However, the impact of HBOC-201 infusion with or without inhaled nitric oxide on
      pulmonary vascular tone has not yet been examined. METHODS: The pulmonary and
      systemic hemodynamic effects of breathing nitric oxide both before and after the
      administration of HBOC-201 were determined in healthy, awake lambs. RESULTS:
      Intravenous administration of HBOC-201 (12 ml/kg) induced prolonged systemic and
      pulmonary vasoconstriction. Pretreatment with inhaled nitric oxide (80 parts per
      million [ppm] for 1 h) prevented the HBOC-201--induced increase in mean arterial
      pressure but not the increase of pulmonary arterial pressure, systemic vascular
      resistance, or pulmonary vascular resistance. Pretreatment with inhaled nitric
      oxide (80 ppm for 1 h) followed by breathing a lower concentration of nitric
      oxide (5 ppm) during and after HBOC-201 infusion prevented systemic and pulmonary
      vasoconstriction without increasing methemoglobin levels. CONCLUSIONS: These
      findings demonstrate that pretreatment with inhaled nitric oxide followed by
      breathing a lower concentration of the gas during and after administration of
      HBOC-201 may enable administration of an acellular hemoglobin substitute without
      vasoconstriction while preserving its oxygen-carrying capacity.

PMID- 19104179
TI  - CU-2010--a novel small molecule protease inhibitor with antifibrinolytic and
      anticoagulant properties.
AB  - BACKGROUND: In cardiac surgery, the contact of blood with the artificial surfaces
      of the cardiopulmonary bypass results in activation of coagulation, fibrinolysis,
      and platelets, which is recognized as reason for increased bleeding tendency.
      Antifibrinolytics like tranexamic acid or the broad-spectrum protease inhibitor
      aprotinin attenuate this response. The marketing of aprotinin has been suspended
      after a recent clinical trial suggested increased risks associated with
      aprotinin. Moreover, aprotinin is a protein of animal origin and has antigenic
      properties. As a result, alternative antifibrinolytic compounds are desirable.
      METHODS: This in vitro study compared the antifibrinolytic efficacy of the
      synthetic small molecule CU-2010 with aprotinin and tranexamic acid.
      Antifibrinolytic activity in plasma and whole blood of ten healthy volunteers was
      examined with a turbidometric method and with tissue factor-activated
      thromboelastometry (ROTEM; Pentapharm, Munich, Germany). In addition,
      anticoagulant effects were assessed through measurement of plasma and whole blood
      clotting times and thrombin generation. RESULTS: With its high affinity for
      plasmin (Ki, 2 nM), CU-2010 inhibited fibrinolysis comparable to aprotinin (Ki, 4
      nM) and was ten times more potent than tranexamic acid. CU-2010 also inhibited
      plasma kallikrein (Ki < 1 nM) and factors Xa (Ki, 45 nM) and XIa (Ki, 18nM),
      which was reflected in prolongation of coagulation times and an attenuation of
      thrombin generation. CONCLUSION: These findings suggest that CU-2010 has similar
      antifibrinolytic potency compared to aprotinin, is more potent than tranexamic
      acid, and possesses some anticoagulant effects.

PMID- 19104180
TI  - Liability associated with obstetric anesthesia: a closed claims analysis.
AB  - BACKGROUND: Obstetrics carries high medical liability risk. Maternal death and
      newborn death/brain damage were the most common complications in obstetric
      anesthesia malpractice claims before 1990. As the liability profile may have
      changed over the past two decades, the authors reviewed recent obstetric claims
      in the American Society of Anesthesiologists Closed Claims database. METHODS:
      Obstetric anesthesia claims for injuries from 1990 to 2003 (1990 or later claims;
      n = 426) were compared to obstetric claims for injuries before 1990 (n = 190).
      Chi-square and z tests compared categorical variables; payment amounts were
      compared using the Kolmogorov-Smirnov test. RESULTS: Compared to pre-1990
      obstetric claims, the proportion of maternal death (P = 0.002) and newborn
      death/brain damage (P = 0.048) decreased, whereas maternal nerve injury (P <
      0.001) and maternal back pain (P = 0.012) increased in 1990 or later claims. In
      1990 or later claims, payment was made on behalf of the anesthesiologist in only
      21% of newborn death/brain damage claims compared to 60% of maternal death/brain
      damage claims (P < 0.001). These payments in both groups were associated with an
      anesthesia contribution to the injury (P < 0.001) and substandard anesthesia care
      (P < 0.001). Anesthesia-related newborn death/brain damage claims had an
      increased proportion of delays in anesthetic care (P = 0.001) and poor
      communication (P = 0.007) compared to claims unrelated to anesthesia. CONCLUSION:
      Newborn death/brain damage has decreased, yet it remains a leading cause of
      obstetric anesthesia malpractice claims over time. Potentially preventable
      anesthetic causes of newborn injury included delays in anesthesia care and poor
      communication between the obstetrician and anesthesiologist.

PMID- 19104181
TI  - Expression profile of nerve growth factor after muscle incision in the rat.
AB  - BACKGROUND: Previous studies have demonstrated that nerve growth factor (NGF) is
      an important mediator of pathologic pain. Many studies have focused on cutaneous
      mechanisms for NGF-induced hyperalgesia; few have examined its contribution in
      deeper tissues like muscle. This study examined pain behaviors and the expression
      of NGF in incised hind paw flexor digitorum brevis muscle. METHODS: Adult Sprague
      Dawley rats were pretreated with anti-NGF peptibody and underwent skin or skin
      plus deep fascia and muscle incision. Guarding pain behaviors were measured.
      Muscle NGF messenger RNA (mRNA) was measured by reverse-transcriptase polymerase
      chain reaction. Changes in NGF protein expression were measured using Western
      blot, enzyme-linked immunosorbent assay, and immunohistochemistry. In situ
      hybridization for NGF mRNA was also performed. RESULTS: Pretreatment with anti
      NGF peptibody (100 mg/kg) decreased the guarding behavior caused by deep fascia
      and muscle incision. Muscle NGF mRNA increased abruptly 2 h after incision and
      was the same as control by postoperative day 1. NGF protein increased from 4 h
      after incision and was sustained for several days. NGF was localized in many
      calcitonin gene-related peptide-positive axons, few N52-positive axons, but not
      isolectin B4-positive axons in incised muscle. The sources of NGF mRNA included
      keratinocytes in epidermis and fibroblasts in deeper tissues. CONCLUSION:
      Fibroblasts adjacent to the injury are sources of NGF in incised muscle. NGF is
      upregulated by incision of muscle and contributes to guarding pain behavior.

PMID- 19104182
TI  - Comparison of continuous infusion versus automated bolus for postoperative
      patient-controlled analgesia with popliteal sciatic nerve catheters.
AB  - BACKGROUND: This investigation was designed to compare a new methodology of
      automated regular bolus with a continuous infusion of local anesthetic for
      continuous popliteal sciatic block; both regimens were combined with patient
      controlled analgesia (PCA). METHODS: Fifty patients undergoing hallux valgus
      repair were randomly allocated to receive an infusion of 0.125% levobupivacaine
      administered through a popliteal catheter as an automated regular bolus (n = 25)
      or as a continuous infusion (n = 25), both combined with PCA. Postoperative pain
      scores, incremental doses delivered by the PCA, local anesthetic consumed per
      hour, and the need for rescue tramadol analgesia were recorded. RESULTS: Both
      dosing regimens provided similar postoperative analgesia. Consumption of local
      anesthetic (5.14 ml/h, 5-5.75 ml/h) and dose request from the PCA (1, 0-5.4) was
      lower in the automated bolus group as compared to the continuous infusion group
      (5.9 ml/h, 5.05-7.8 ml/h; doses by PCA: 6.5, 0-20.5; P < 0.05). The need for
      rescue tramadol was similar in the two groups. CONCLUSION: In continuous
      popliteal sciatic block, local anesthetic administered as an automated regular
      bolus in conjunction with PCA provided similar pain relief as a continuous
      infusion technique combined with PCA; however, the new dosing regimen reduced the
      need for additional PCA and the overall consumption of local anesthetic.

PMID- 19104183
TI  - Activation of p38 mitogen-activated protein kinase in spinal microglia
      contributes to incision-induced mechanical allodynia.
AB  - BACKGROUND: Recent studies have implicated the activation of stress-activated
      mitogen-activated protein kinase (MAPK) p38 in spinal microglial cells for
      development of neuropathic and inflammatory pain. The aim of the present study
      was to investigate whether phosphorylation of p38 (p-p38) also mediates
      mechanical allodynia and thermal hyperalgesia induced by plantar incision.
      METHODS: After rats received a plantar incision surgery, mechanical allodynia and
      thermal hyperalgesia were determined by von Frey filaments and radiant heat,
      respectively, and the number of p-p38 immunoreactive cells in the dorsal horn was
      quantified to determine p38 activation at different time points after incision.
      The p38 inhibitor FR167653 was administered intrathecally 30 min before hind paw
      plantar incision to determine the role of p38 in postoperative pain. RESULTS: A
      significant increase in number of p-p38 immunoreactive cells was observed in the
      ipsilateral L4-5 spinal dorsal horn from 1 h to 3 days after the incision. p-p38
      was found predominantly in microglia. However, microglial activation (assessed by
      OX-42 upregulation) was not evident until 3 days after plantar incision.
      Intrathecal pretreatment of FR167653 attenuated incision-induced mechanical
      allodynia from 1 h to day 2 and significantly reduced activation of p38 in the
      dorsal horn 1 day after plantar incision. However, FR167653 only inhibited heat
      hyperalgesia at an early time point. CONCLUSIONS: Plantar incision-induced
      mechanical allodynia can be prevented by the p38 inhibitor. Our results suggest
      that p38 activation in spinal microglia play a role in incision-induced
      mechanical allodynia in rats. Therefore, p38 inhibition may be useful in treating
      postsurgical pain.

PMID- 19104184
TI  - Modulation of opioid actions by nitric oxide signaling.
AB  - Nitric oxide (NO) plays pivotal roles in controlling physiological functions,
      participates in pathophysiological intervention, and is involved in mechanisms
      underlying beneficial or untoward actions of therapeutic agents. Endogenous
      nitric oxide is formed by three isoforms of nitric oxide synthase: endothelial,
      neurogenic and inducible. The former two are constitutively present mainly in the
      endothelium and nervous system, respectively, and the latter one is induced by
      lipopolysaccharides or cytokines mainly in mitochondria and glial cells.
      Constitutively formed nitric oxide modulates the actions of morphine and related
      analgesics by either enhancing or reducing antinociception. Tolerance to and
      dependence on morphine or its withdrawal syndrome are likely prevented by nitric
      oxide synthase inhibition. Information concerning modulation of morphine actions
      by nitric oxide is undoubtedly useful in establishing new strategies for
      efficient antinociceptive treatment and for minimizing noxious and unintended
      reactions.

PMID- 19104185
TI  - Infectious risk of continuous peripheral nerve blocks.

PMID- 19104186
TI  - Acute airway obstruction caused by the new single use Laryngeal Mask Airway
      Supreme.

PMID- 19104187
TI  - Technique of lung isolation for whole lung lavage in a child with pulmonary
      alveolar proteinosis.

PMID- 19104189
TI  - STOP questionnaire warrants CAUTION sign.

PMID- 19104190
TI  - Concerns about the validation of the Berlin Questionnaire and American Society of
      Anesthesiologist checklist as screening tools for obstructive sleep apnea in
      surgical patients.

PMID- 19104193
TI  - Effects of an intervention aimed at improving nurse-patient communication in an
      oncology outpatient clinic.
AB  - In an ever more burdened healthcare system, there is an urgent need to
      investigate whether patients benefit from the resources allocated to nurses'
      communication skills training in terms of improved patient outcomes. This study
      aimed to evaluate a standardized two 2-day (33 hours) communication skills
      training program in nursing cancer care. Twenty-four nurses in an oncology
      outpatient clinic participated and were randomly assigned to the intervention
      program or a control group. A total of 413 patients treated in the clinic during
      2 recruitment periods (before and after the communication skills training)
      completed a questionnaire package assessing the nurse-patient relationship,
      psychological well-being, and cancer-related self-efficacy. Nurse group
      differences in change scores between time points (baseline, 1 week, and 3 months
      after the communication skills training) on measures related to communication and
      work-related stress were all nonsignificant. Time-by-group analyses of patient
      data showed no training effect on patient perception of nurse empathy and
      attentiveness, and we found no training effect on patients' anxious/depressed,
      angry, or positive mood, as well as no effect on cancer-related self-efficacy.
      The results were unable to support the hypotheses that nurse communication skills
      training would be associated with improved nurse and patient outcomes.

PMID- 19104194
TI  - Accommodating the diverse cultural needs of cancer patients and their families in
      palliative care.
AB  - Cultural issues have become an increasingly important consideration in
      healthcare. Such cultural issues, however, are underresearched in Australia,
      especially in palliative care. This study has sought to address this gap,
      exploring the social construction of cultural issues in palliative care by
      oncology nurses. A grounded theory approach was used. Semistructured interviews
      with 7 Australian oncology nurses provided the data for the study. The core
      category emerging from the study was that of accommodating cultural needs whereby
      to meet patients' specific cultural requirements, nurses actively found ways to
      accommodate the needs of patients and their families. This process often included
      compromise and negotiation whereby limits were set. In addition, the use of cross
      cultural communication strategies emerged from the data as an important feature
      of cultural care. A series of subcategories were also identified as factors that
      could influence the process by which nurses would accommodate cultural needs.

PMID- 19104195
TI  - The World Cancer Declaration 2008 needs and deserves active support from oncology
      nurses.

PMID- 19104196
TI  - Worry and the formation of cognitive representations of illness in individuals
      undergoing surgery for suspected lung cancer.
AB  - Worry involving repetitive thoughts about threats and concerns is prevalent when
      confronted with a life-threatening illness such as cancer. Worry may contribute
      to the formation of negative cognitive representations of illness that can have a
      detrimental effect on behavioral and adaptive outcomes. The study examined for
      the first time (a) the relationship between worry and early formation of
      cognitive representations of illness in individuals with suspected lung cancer
      over the presurgical and postsurgical period and (b) associations between worry
      and anxiety, sex, age, and educational level. Correlational statistical analyses
      were used to assess worry and cognitive representations in 42 individuals before
      lung surgery and again 3 weeks postsurgery. Higher worry was significantly
      related to more threatening content in multiple illness domains. Repeated
      measures analysis of variance using high- and low-worry strata showed significant
      interactions between worry and time on certain illness domains indicating that
      high worry was associated with increased threat and negative contents in
      cognitive representations of illness over time. Multiple regression analyses
      showed that trait anxiety was the only significant predictor of worry in a
      regression model including age, sex, education, and anxiety before surgery.
      Findings suggest that higher worry at time of diagnosis is associated with the
      development of negative and more threatening contents in cognitive
      representations of illness in individuals with suspected lung cancer.

PMID- 19104197
TI  - An in-depth exploration of information-seeking behavior among individuals with
      cancer: part 1: understanding differential patterns of active information
      seeking.
AB  - The purpose of this 2-part paper was to describe individuals' health information
      seeking behavior (HISB) patterns that emerged from our grounded theory study.
      Thirty individual interviews and 8 focus groups were conducted with individuals
      diagnosed with cancer. Analysis was characterized by constant comparison diagram,
      an evolving coding scheme, and ultimately the generation of a grounded theory of
      HISB patterns. Five HISB patterns were identified: (1) intense information
      seeking-a keen interest in detailed cancer information; (2) complementary
      information seeking--the process of getting "good enough" cancer information; (3)
      fortuitous information seeking--the search for cancer information mainly from
      others diagnosed with cancer; (4) minimal information seeking--a limited interest
      for cancer information; and (5) guarded information seeking--the avoidance of
      some cancer information. Part 1 focuses on describing the first 3 HISB patterns
      considered to illustrate variations in active information seeking. Each pattern
      is explained, including the type, amount, and sources of information sought. This
      analysis documents variations in active HISB often overlooked in the cancer
      literature. Findings may assist healthcare professionals in tailoring their
      informational interventions according to a patient's preferred HISB pattern.
      Furthermore, findings may inform the refinement of instruments measuring HISB to
      include variations in active information seeking.

PMID- 19104199
TI  - An in-depth exploration of information-seeking behavior among individuals with
      cancer: part 2: understanding patterns of information disinterest and avoidance.
AB  - This is the second of a 2-part article describing differential health information
      seeking behavior (HISB) patterns within the context of a cancer diagnosis that
      emerged in our grounded theory study. Data from 30 semistructured interviews and
      8 focus groups with individuals diagnosed with breast, prostate, or colorectal
      cancer were analyzed using constant comparison analysis, diagramming, and open,
      axial, and selective coding. In part 1, 3 HISB patterns illustrating variation in
      active information-seeking behavior were described: (1) intense information
      seeking a keen interest in detailed cancer information, (2) complementary
      information seeking the process of getting "good enough" cancer information, and
      (3) fortuitous information seeking the search for cancer information mainly from
      others diagnosed with cancer. Part 2 describes 2 additional patterns coined in
      this study as minimal information-seeking behavior limited interest for cancer
      information and guarded information-seeking behavior avoidance of certain types
      of cancer information. Part 2 challenges traditional views that consider
      disinterest and avoidance as similar concepts subsumed under "blunting." Findings
      may be used to refine informational interventions and measurement strategies to
      best differentiate between cancer information avoidance and disinterest.

PMID- 19104200
TI  - The impact of a multimedia informational intervention on healthcare service use
      among women and men newly diagnosed with cancer.
AB  - This quasi-experimental longitudinal study documented the impact of a
      comprehensive cancer informational intervention using information technology on
      healthcare service use among individuals newly diagnosed with cancer. Women with
      breast cancer (n = 205) and men with prostate cancer (n = 45) were recruited
      within 8 weeks of diagnosis at 4 university teaching hospitals in Montreal,
      Quebec, Canada. The intervention group (n = 148) received a 1-hour training on
      information technology use, a CD-ROM on cancer, and a list of reputable cancer
      related Web sites. The intervention material was available for a period of 8
      weeks. The control group (n = 102) received usual care. Self-reported
      questionnaires were completed at T1 (baseline), T2 (1 week after intervention),
      and T3 (3 months after intervention). Using multivariate statistics, the
      experimental group reported significantly more satisfaction with cancer
      information received compared to the control group. No significant differences
      were found between experimental and control groups in their reliance on
      healthcare services. However, women as opposed to men spent more time with
      nurses, were more satisfied with cancer information received, and relied more
      heavily on health services. Future research would explore whether the latter
      observations reflect genuine sex differences or are more contingent on the
      specific cancer diagnosis.

PMID- 19104201
TI  - Taste and smell changes in patients receiving cancer chemotherapy: distress,
      impact on daily life, and self-care strategies.
AB  - Few studies have described how patients receiving chemotherapy experience
      taste/smell changes (TSCs). Food and meal situations have important meaning
      beyond nutrition, so these common symptoms may affect daily lives. This study
      aims to investigate distress and impact on daily life from TSCs in patients
      receiving cancer chemotherapy, analyze reported levels of distress and impact on
      daily life from TSCs with regard to sociodemographic and clinical factors, and
      explore patients' reports of self-care strategies and communication with staff.
      The 340 patients reporting TSCs on a multicenter survey (n = 518) were grouped
      into subsets by level of TSC-related distress and impact on daily life, which
      served as the basis for statistical comparison. Written comments were analyzed
      inductively using content analysis. Nearly one-third of participating patients
      reported both high levels of distress and impact on daily life (high distress and
      high impact on daily life [HDHI]) from TSCs. The HDHI subset reported other
      symptoms more often than others did (P = .01) and also more often responded to
      open questions about distress, impact, and self-care strategies (P = .01).
      Taste/smell changes were not always reported to staff, even in the HDHI subset.
      The specific aspects of TSCs resulting in distress and impact on daily life
      varied greatly, affecting both psychological and somatic aspects, with little
      consensus and great individual differences described in self-care strategies. The
      variety of distress, impact, and strategies used to alleviate TSCs clarifies the
      importance of situational meaning.

PMID- 19104202
TI  - Psychological reactions to progression of metastatic breast cancer--an interview
      study.
AB  - Knowledge about how patients experience their situation at the point of disease
      progression after first-line chemotherapy is limited. It is important to
      investigate this area to better understand and support women with advanced-stage
      disease. The study explored psychological reactions and coping on disease
      progression after first-line chemotherapy among women with metastatic breast
      cancer. Interviews were held with 20 patients with breast cancer who were
      included in a randomized study of first-line chemotherapy for metastatic breast
      cancer. Three themes emerged. "Before the information": most of the women
      reported symptoms related to the disease progression before information about
      treatment failure. Thus, they were not surprised by the information. "Immediate
      after information": a range of psychological reactions were described. Most
      patients experienced sadness, disappointment, and setback in view of disease
      progress. Anxiety and worry about the future were reported. "Life after being
      informed of disease progression": Various strategies to cope with their situation
      were used, for example, work, social support, and church attendance. All women
      had disease progression. Worry was the most common emotional response. A number
      of strategies were used to cope with the situation. Most of the women responded
      with acceptance.

PMID- 19104204
TI  - Family caregiver engagement in a coping and communication support intervention
      tailored to advanced cancer patients and families.
AB  - We describe family caregiver (FCG) participation in a tailored coping and
      communication support intervention for advanced cancer patients and families.
      Preliminary descriptive data on characteristics and patterns of early engagement
      in the intervention for 132 FCGs are presented. Engagement assessed at an initial
      in-person meeting and the following 6 weeks includes problems raised, strategies
      used, and initiation, frequency, and mode of contact. A sizable proportion of
      FCGs were male, African American, and nonspouse. The FCGs had modest scores on a
      standard survey measure of burden yet volunteered caregiving demands as their
      primary problem. Other problems raised initially by more than 40% of the sample
      included psychological, practical, and communication with healthcare providers.
      Few reported physical and psychosocial difficulties. Engagement preferences
      expressed at the initial meeting largely mapped with actual engagement during the
      6 weeks of intervention. Most FCGs were actively engaged during follow-up. Some
      (14%) did not opt for coping and communication support during this early
      treatment phase. This intervention is expected to affect quality of care and
      quality-of-life outcomes for FCGs over time from patient diagnosis to end of
      life. Findings will guide modification and dissemination of this intervention
      primarily in cancer clinics for the underserved.

PMID- 19104203
TI  - Predictors of breast examination practices of Chinese immigrants.
AB  - Breast cancer is a significant threat to Chinese women living in the United
      States. The purposes of this study are, first, to examine the relationships among
      breast cancer risk knowledge, general cancer beliefs, and breast examination
      practices and, second, to determine the predictors of breast examination
      practices among Chinese women in New York. The study offers a descriptive
      approach that makes use of a correlation cross-sectional survey (N = 135). Five
      significant predictors are related to breast examination practices as a result of
      the study findings: age, acculturation, private insurance status, legal status,
      and length of stay in New York. Findings show that women who have regular breast
      examinations most likely belong to older generations, as compared with their
      younger peers. Study findings suggest that healthcare providers must become more
      culturally sensitive to the practices and needs of Chinese immigrants. Evidently,
      providing information regarding cancer prevention targeted for female Chinese
      immigrants can help increase use of cancer screening tests.

PMID- 19104205
TI  - Relief of radiation-induced oral mucositis in head and neck cancer.
AB  - This study was a prospective, randomized clinical trial carried out to explore
      the efficacy of payayor in the prevention and relief of radiation-induced oral
      mucositis compared with benzydamine. Sixty patients with head and neck cancer,
      who have started to receive radiotherapy and met predetermined criteria, were
      randomly assigned into each group to use assigned products 3 times a day from the
      first to the last day of radiation. The first group used glycerin payayor, a Thai
      prepared herbal product, by dripping it into the mouth. Another group rinsed
      their mouths with benzydamine hydrochloride. The World Health Organization
      Mucositis Grading System was used to assess oral status every week and 2 weeks
      after radiation. Comparison of time to the onset, pain, severity, xerostomia,
      postponement of treatment, satisfaction of the solution, and body weight between
      the 2 groups was performed by t test. The average time to the onset of oral
      mucositis in the payayor group was significantly later, and its severity and pain
      score were less than those of the benzydamine group throughout the study period.
      Significantly higher satisfaction with the solution and higher body weight at the
      end of the study were shown in the payayor group. Payayor seemed to be superior
      to benzydamine for preventing and relieving radiation-induced oral mucositis.

PMID- 19104206
TI  - The clinical research enterprise in critical care: what's right, what's wrong,
      and what's ahead?
AB  - Intensivists have been remarkably successful in using randomized controlled
      trials to assess aspects of current practice. Unfortunately, this success has not
      been mirrored in trials of new pharmacotherapy, despite convincing
      pathophysiological rationales and encouraging preliminary studies.
      Misunderstandings of biological processes and flawed early clinical studies have
      led to the almost universal failure of fundamentally new treatments subjected to
      large phase III trials, despite their sound methodology. Compounding these
      problems is the tendency for new approaches to be either implemented widely on
      the basis of relatively poor studies or ignored despite strong supporting
      evidence. Having mastered the principles of evidence-based medicine in assessing
      existing therapy, intensivists have established a strong foundation. Critical
      care medicine must now embrace the challenge of translating a more solid
      understanding of basic disease mechanisms into widely implemented treatments.

PMID- 19104207
TI  - Translational research in the development of novel sepsis therapeutics: logical
      deductive reasoning or mission impossible?
AB  - The successful translation of promising research findings from basic research
      laboratories into useful clinical products for the management of septic patients
      has proven to be a daunting challenge. The complexity and variability of the
      clinical entity referred to as sepsis makes it intrinsically difficult to model
      preclinical systems and predict efficacy of potentially useful, experimental,
      therapeutic agents. Technological innovations in microarrays, microfluidics, and
      nanotechnology make it feasible to study the evolution of sepsis in small animal
      models in considerable detail. The recognized limitations of standard preclinical
      platforms used to study sepsis have lead to innovative approaches to study sepsis
      in silico, and in more complex and clinically more valid ex vivo tissue perfusion
      models and animal systems. It is abundantly clear that sepsis researchers need to
      do a better job informing clinicians about the possible benefits and potential
      risks of new treatment interventions as they traverse the gap between the bench
      and the bedside.

PMID- 19104208
TI  - Complex intensive care unit interventions.
AB  - The use of randomized controlled trials are useful for comparing a simple
      intervention such as a new drug or procedure. However, complex interventions such
      as a new system to evaluate early intervention in serious illness usually require
      complex research methodologies. An intensive care unit is a complex organization
      and patient care can be influenced by many factors such as standards of nursing
      care and staff morale within the unit. Some of these factors may be as important,
      or even more important, than a simple intervention such as a new drug. To answer
      these questions, we will have to rely not only on complex quantitative research
      methodologies but also qualitative or a combination of both quantitative and
      qualitative research.

PMID- 19104209
TI  - The unique challenges of enrolling patients into multiple clinical trials.
AB  - Multiple interventions are implemented to save the lives of a critically ill
      patients. The therapeutic value of most of these interventions remains untested.
      Enrollment of patients in the intensive care unit into multiple studies could
      improve the efficiency of testing interventions in the intensive care unit.
      Unfortunately, enrollment of intensive care unit patients into multiple studies
      is often discouraged. If the same patient is enrolled into more than one study,
      there is a risk that interactions between interventions could lead to false
      conclusions. In addition, there is a belief that the families of critically ill
      patients might feel overly stressed if they are repeatedly approached for
      consent. This article provides a rationale for enrolling intensive care unit
      patients into multiple clinical trials. Factorial designs are efficient, but
      their inherent limitations must be noted. The little evidence that is available
      shows that most patients would enroll in multiple studies and do not feel overly
      stressed by participating in more than one study. Modifications to subject
      consent, data collection, and data analysis for coenrollment could facilitate it.
      In conclusion, more vigorous promotion of thoughtful coenrollment policies could
      increase the efficiency of critical care research.

PMID- 19104210
TI  - Improving clinical trials of long-term outcomes.
AB  - There is an increasing evidence that survivors of critical illness suffer from
      impaired health-related quality of life. There are relatively few studies that
      have evaluated the effect of interventions in clinical trials to improve these
      long-term outcomes. Studies to improve long-term outcomes after critical illness
      face many of the same challenges encountered in studies designed to improve
      shorter term outcomes in the intensive care unit. These include an incomplete
      understanding of the causal mechanisms involved in post-intensive care unit
      impairment, trouble in identifying patients ill enough to benefit from an
      intervention but whose impairment is not fixed, and identifying proper outcome
      variables. There are, however, unique challenges to clinical trials including
      bias from competing mortality and incomplete follow-up. Research interest in
      developing interventions to improve long-term outcome after critical illness is
      in its infancy and it is too early to make strong clinical recommendations.
      Multiple potential treatment areas exist, both within the intensive care unit and
      after patients leave the hospital, for intensivists to target. Those interested
      in this area should collaborate to build on the lessons from effective
      multidisciplinary programs developed to treat other diseases.

PMID- 19104211
TI  - Improving clinical trials in the critically ill: unique challenge--sepsis.
AB  - OBJECTIVE: This article aimed at providing suggestions to improve the success
      rate of future sepsis trials. DESIGN: Systematic review. INTERVENTION: None.
      MEASUREMENTS AND MAIN RESULTS: CENTRAL (The Cochrane Library Issue 2, 2007) was
      searched using "sepsis" OR "severe sepsis" OR "septic shock" as search terms. The
      search was restricted to studies designed and conducted in adults with severe
      sepsis or septic shock after June 1992, published before September 2007, and
      powered for survival analysis. Twenty-seven trials were included and analyzed.
      The author suggested six key points for the design and conduct of future sepsis
      trials: 1) avoid mixing patients with severe sepsis and septic shock; 2) restrict
      time window to less than 24 hrs from onset of the first organ dysfunction or
      shock; 3) include only undisputable sepsis; 4) use the Sepsis-related Organ
      Failure Assessment score for eligibility; 5) include a first interim analysis
      after enrollment of 25% of the planned sample size to check the actual basal risk
      of death and to recalculate the number of patients needed; 6) strictly control
      for concomitant treatments on the basis of the Surviving Sepsis Campaign.
      CONCLUSIONS: There is a need to limit the sources of heterogeneity in sepsis
      trials by a better definition of target populations, by a better estimation of
      basal risk of death, and by controlling cointerventions.

PMID- 19104212
TI  - Unique challenges in clinical trials in traumatic brain injury.
AB  - Clinical trials in traumatic brain injury have shown little success in providing
      an evidence base for the introduction of successful new therapies into clinical
      practice. In addition to the problems that are common to all such studies in
      critical illness, trials in traumatic brain injury are complicated by the
      extremely short temporal window for intervention, failure of many candidate drugs
      to cross the blood-brain barrier, ethical and regulatory obstacles associated
      with research in subjects who cannot provide consent, the tendency to use small
      sample sizes in anticipation of unrealistic treatment benefits, and difficulty in
      translating experimental success into clinical practice. This article reviews the
      potential causes of these problems and suggests some solutions. These include the
      changes in regulatory frameworks that are making waived consent an acceptable
      strategy once more, and an increasing trend toward appropriately large trials.
      Other encouraging developments include the increasing use of human experimental
      medicine strategies before phase III trials to assess blood-brain barrier
      penetration and dose ranging, and provide proof of concept and proof of
      mechanism. Novel approaches to trial design, such as sliding dichotomy, coupled
      with robust outcome prediction models, can increase statistical power and improve
      trial design.

PMID- 19104213
TI  - Conducting clinical trials in pediatrics.
AB  - Conducting clinical trials in pediatric critical care patients are necessary both
      to determine the value of new treatment strategies and to improve clinical
      outcomes. However, there are significant challenges to clinicians, parents, and
      child subjects. There is a serious danger to children through exposure to
      unforeseen risk as a result of lack of pediatric trials if "trickle down" from
      adult treatments is permitted. The relatively small size of the pediatric
      critical care population and relatively low mortality rates limit the utility of
      mortality as a primary trial outcome in many trials. Innovative trial designs
      including incorporation of nonfatal outcome measures are increasingly being
      developed. Increasingly, effective research collaborations are developing either
      for specific clinical trials or to form the base from which clinical trials are
      commissioned and supervised. Involvement of children and parents in the
      development of clinical trials is recommended and valued both by ethical review
      boards and patient/parent support organizations.

PMID- 19104214
TI  - Qualitative research: adding drive and dimension to clinical research.
AB  - Qualitative research and its methods stem from the social sciences and can be
      used to describe and interpret complex phenomena that involve individuals' views,
      beliefs, preferences, and subjective responses to places and people. Thus,
      qualitative research explores the many subjective factors that may influence
      patient outcomes, staff well-being, and healthcare quality, yet fail to lend
      themselves to the hypothesis-testing approach that characterizes quantitative
      research. Qualitative research is valuable in the intensive care unit to explore
      organizational and cultural issues and to gain insight into social interactions,
      healthcare delivery processes, and communication. Qualitative research generates
      explanatory models and theories, which can then serve to devise interventions,
      whose efficacy can be studied quantitatively. Thus, qualitative research works
      synergistically with quantitative research, providing new impetus to the research
      process and a new dimension to research findings. Qualitative research starts
      with conceptualizing the research question, choosing the appropriate qualitative
      strategy, and designing the study; rigorous methods specifically designed for
      qualitative research are then used to conduct the study, analyze the data, and
      verify the findings. The researcher is the data-collecting instrument, and the
      data are the participants' words and behaviors. Data coding methods are used to
      describe experiences, discover themes, and build theories. In this review, we
      outline the rationale and methods for conducting qualitative research to inform
      critical care issues. We provide an overview of available qualitative methods and
      explain how they can work in close synergy with quantitative methods. To
      illustrate the effectiveness of combining different research methods, we will
      refer to recent qualitative studies conducted in the intensive care unit.

PMID- 19104215
TI  - Disseminating clinical trial results in critical care.
AB  - Efficient translation of clinical evidence into clinical practice is among the
      greatest challenges to evidence-based medicine. The field of knowledge transfer
      seeks to understand the barriers to evidence uptake and develop new methods to
      effectively disseminate clinical trial results. Traditionally, barriers to
      evidence-based practice are categorized into those of knowledge, attitudes, and
      behavior. Efforts to improve translation of evidence into practice should uncover
      and address each of these barriers and be customized to the specific
      intervention. To help aid knowledge transfer, interventions in clinical trials
      should be as simple as possible and answer questions important to actual
      caregivers. Potentially innovative methods for improving knowledge transfer
      include expanding community research networks, clinical registries to monitor
      evidence uptake, and community-based participatory research. It is essential that
      investigators conducting clinical trials prioritize knowledge transfer to ensure
      that new therapies in critical care are actually reaching the critically ill.

PMID- 19104216
TI  - Postregistration trials: should we? How do we?
AB  - Postregistration trials or postmarketing or phase IV trials are tools to
      investigate any treatment that is already approved and is, therefore, available
      for prescription use. The main objectives of these trials are typical
      effectiveness, more structured surveillance for uncommon or rare side effects,
      and the potential development of new indications. Several issues need to be
      addressed in the postregistration phase of the evaluation of a therapeutic
      treatment. Among those we will focus on two ethical challenges: reporting bias
      from industry-sponsored research and use of placebo as one of the arms in
      controlled studies where proven treatment already exists. The review of this
      topic is particularly relevant in the field of critical care because it is
      ongoing in the debate about the opportunity to perform a new placebo-controlled
      study with the recombinant human activated protein C (activated drotrecogin alfa
      activated protein C). In fact, despite the approval of activated protein C for
      treatment of patients with severe sepsis and high risk of death, several issues
      regarding the efficacy and safety of its administration have been recognized by
      several investigators to the point that the European Medicines Agency asked for a
      new placebo-controlled study to further clarify the benefit/risk profile of
      activated protein C.

PMID- 19104217
TI  - Better infrastructure: industry-academia partnerships--a marriage of convenience?
AB  - The successful design and completion of clinical trials often requires
      participation of both industry and academia. Although there may be differing
      priorities for academic and industry participants, both bring important insights
      and resources to the clinical trial effort. Although industry generally is
      primarily responsible for preclinical development and funding of the study and
      academia for patient recruitment and participation in the data safety monitoring
      board and clinical coordinating center, there are also a number of important
      areas, including protocol design, data analysis, and manuscript preparation where
      both academia and industry can supply important insights. Inherent tensions may
      exist in the academic-industry relationship, including important issues relating
      to conflict of interest for both academic and industry participants.
      Nevertheless, the academic-industry partnership, if appropriately organized, can
      perform in a synergistic fashion, allowing exploration of novel therapies,
      elucidation of important mechanisms, and greater understanding of critical
      illness through using combined approaches that generate insights unable to be
      provided by either partner alone.

PMID- 19104218
TI  - Using systems biology to simplify complex disease: immune cartography.
AB  - What if there was a rapid, inexpensive, and accurate blood diagnostic that could
      determine which patients were infected, identify the organism(s) responsible, and
      identify patients who were not responding to therapy? We hypothesized that
      systems analysis of the transcriptional activity of circulating immune effector
      cells could be used to identify conserved elements in the host response to
      systemic inflammation, and furthermore, to discriminate between sterile and
      infectious etiologies. We review herein a validated, systems biology approach
      demonstrating that 1) abdominal and pulmonary sepsis diagnoses can be made in
      mouse models using microarray (RNA) data from circulating blood, 2) blood
      microarray data can be used to differentiate between the host response to Gram
      negative and Gram-positive pneumonia, 3) the endotoxin response of normal human
      volunteers can be mapped at the level of gene expression, and 4) a similar
      strategy can be used in the critically ill to follow septic patients and
      quantitatively determine immune recovery. These findings provide the foundation
      of immune cartography and demonstrate the potential of this approach for rapidly
      diagnosing sepsis and identifying pathogens. Further, our data suggest a new
      approach to determine how specific pathogens perturb the physiology of
      circulating leukocytes in a cell-specific manner. Large, prospective clinical
      trails are needed to validate the clinical utility of leukocyte RNA diagnostics
      (e.g., the riboleukogram).

PMID- 19104219
TI  - Investigator-led clinical research consortia: the Canadian Critical Care Trials
      Group.
AB  - Advances in the care of critically ill patients are dependent upon rigorous
      clinical research undertaken to characterize natural history and risk factors,
      and determine optimal approaches to the management of the diseases of the
      critically ill patient. The Canadian Critical Care Trials Group (CCCTG) was
      formed in 1989 to foster such research. It has grown to become a national,
      multidisciplinary organization with more than 100 members, and more than 3 dozen
      active research programs. Its members have been highly successful in obtaining
      funding for, completing, and publishing well-designed studies that have informed
      international practice in areas such as transfusion, stress ulcer prophylaxis,
      long term outcomes from acute respiratory distress syndrome, diagnosis and
      management of infection in the intensive care unit, and end-of-life care. In the
      process, the CCCTG has developed a highly effective culture of scientific
      mentoring, and has served as a model for investigator-led critical care research
      groups around the world. This review summarizes the history, activities,
      approaches, and challenges of the CCCTG, in the conviction that investigator-led
      groups such as ours represent the future of intensive care unit-based research.

PMID- 19104220
TI  - Better infrastructure for critical care trials: nomenclature, etymology, and
      informatics.
AB  - OBJECTIVE: The goals of this review article are to review the importance and
      value of standardized definitions in clinical research, as well as to propose the
      necessary tools and infrastructure needed to advance nosology and medial taxonomy
      to improve the quality of clinical trials in the field of critical care. DATA
      SOURCES: We searched MEDLINE for relevant articles, reviewed those selected and
      their reference lists, and consulted personal files for relevant information.
      DATA SYNTHESIS: When the pathobiology of diseases is well understood, standard
      disease definitions can be extremely specific and precise; however, when the
      pathobiology of the disease is less well understood or more complex, biological
      markers may not be diagnostically useful or even available. In these cases,
      syndromic definitions effectively classify and group illnesses with similar
      symptoms and clinical signs. There is no clear gold standard for the diagnosis of
      many clinical entities in the intensive care unit, including notably both acute
      respiratory distress syndrome and sepsis. There are several types of consensus
      methods that can be used to explicate the judgmental approach that is often
      needed in these cases, including interactive or consensus groups, the nominal
      group technique, and the Delphi technique. Ideally, the definition development
      process will create clear and unambiguous language in which each definition
      accurately reflects the current understanding of the disease state. CONCLUSIONS:
      The development, implementation, evaluation, revision, and reevaluation of
      standardized definitions are keys for advancing the quality of clinical trials in
      the critical care arena.

PMID- 19104221
TI  - Reporting, access, and transparency: better infrastructure of clinical trials.
AB  - Open access to information in medical science and adequate reporting of clinical
      trials may allow investigators and editors to recognize bias in study designs and
      avoid unnecessary duplication of efforts. Unfortunately, most of clinical trials
      are very expensive and are often supported by industries that may have financial
      reasons to hide or partially disclose results. However, investigators and editors
      have a greater interest in publishing results that can immediately change
      clinical practice rather than negative results, thus contributing to facilitate
      publication biases. Several years ago, legislation in several countries mandated
      the registration of clinical trials as an effective means of promoting
      information access and full transparency in medical research. However,
      comprehensive registers have not been adequately supported by law, particularly
      in Europe, where legislation has ironically contributed to fragmented research,
      and dampened its competitiveness and productivity. In this context, appropriate
      strategies help to protect the independence of academic research and ensure full
      transparency in medical science.

PMID- 19104222
TI  - Better translation from bench to bedside: breakthroughs in the individualized
      treatment of cancer.
AB  - This article reflects on progress made in recent years with respect to bench-to
      bedside research in breast cancer. It shows how the advent of molecular oncology
      accompanied by high-throughput experimental methods and "omics" technologies-has
      led researchers to realize that breast cancer is a heterogeneous disease for
      which a "one size fits all" approach to patient treatment is no longer optimal.
      This, in turn, has contributed to a change in thinking about clinical trial
      design. Using several examples of clinical trials being run under the umbrella of
      the Breast International Group, including the recently launched Microarray In
      Node-negative Disease may Avoid ChemoTherapy study and Adjuvant Lapatinib and/or
      Trastuzumab Treatment Optimization study, the article looks at how translational
      research and biological specimen collection has become a central component of
      clinical research design in a relatively short period of time. This, plus an
      evolution in research culture that has resulted in increased international
      collaboration among research networks, groups, and centers, will arm researchers
      with the tools needed to develop truly individualized cancer treatments for
      patients in the future.

PMID- 19104224
TI  - Beyond clinical phenotype: the biologic integratome.
AB  - Current classification of medical diagnosis derives from observational
      correlation between clinical syndromes and pathologic analysis. Limited
      understanding of the molecular determinants of diseases encountered in the
      critically ill remains a major obstacle to the rationale selection of therapeutic
      targets. Indeed, many human diseases reflect a disorder in physiologic processes
      that are known to involve the interaction of many complex control loops and to
      respond to a variety of pharmacologic agents and environmental factors. The
      advent of whole-genome sequencing and other high-throughput technologies have
      changed biomedical research into a data-rich discipline. "Omics" data sets that
      describe virtually all biomolecules in the cell are now publicly available. One
      of the challenges faced by investigators now lies in the interpretation of vast
      amounts of biological data sets to derive fundamental and applied biological
      information about whole systems. As mechanistic understanding of disease requires
      more than an agglomeration of information on the expression and activities of
      disease-associated molecules, network analysis has been applied to biological
      problems. Network analysis of the biological integratome promises to identify
      factors that influence disease phenotype, providing unique insight into disease
      mechanism. Network analysis also provides a mechanistic basis for defining
      phenotypic differences through consideration of unique genetic and environmental
      factors that govern intermediate phenotypes contributing to disease expression.
      Lastly, network analysis offers a unique method for identifying therapeutic
      targets that can alter disease expression.

PMID- 19104223
TI  - Animal models of sepsis: why does preclinical efficacy fail to translate to the
      clinical setting?
AB  - OBJECTIVE: To postulate reasons as to why the benefits seen with novel therapies
      in animal models of sepsis fail to translate to the clinical setting. DATA
      SOURCE: MEDLINE searches and relevant book chapters. DATA SUMMARY: Thousands of
      preclinical trials performed over more than five decades have failed to find more
      than a handful of drugs and techniques that significantly improve outcomes in
      clinical sepsis. We review current concepts surrounding the variety of animal
      models used today, ranging from simple models of acute toxemia to more complex
      models of abdominal sepsis. Differences between animal and human populations are
      also examined including species, age, comorbidity, and the use of supportive
      therapies. Finally, we examine differences between preclinical and clinical trial
      design, and the potential for experimental and publication bias. CONCLUSIONS:
      Animal models of sepsis are still too heterogeneous with regard to type of
      insult, duration, and supportive therapy to be regarded as representative of the
      human condition. Using standardized animal models may eliminate some of the
      differences between animal and human studies, allowing a greater degree of
      translation.

PMID- 19104225
TI  - Toward theragnostics.
AB  - Theragnostics is a treatment strategy that combines therapeutics with
      diagnostics. It associates both a diagnostic test that identifies patients most
      likely to be helped or harmed by a new medication, and targeted drug therapy
      based on the test results. Bioinformatics, genomics, proteomics, and functional
      genomics are molecular biology tools essential for the progress of molecular
      theragnostics. These tools generate the genetic and protein information required
      for the development of diagnostic assays. Theragnostics includes a wide range of
      subjects, including personalized medicine, pharmacogenomics, and molecular
      imaging to develop efficient new targeted therapies with adequate benefit/risk to
      patients and a better molecular understanding of how to optimize drug selection.
      Furthermore, theragnostics aims to monitor the response to the treatment, to
      increase drug efficacy and safety. In addition, theragnostics could eliminate the
      unnecessary treatment of patients for whom therapy is not appropriate, resulting
      in significant drug cost savings for the healthcare system. However, the
      introduction of theragnostic tests into routine health care requires both a
      demonstration of cost-effectiveness and the availability of appropriate
      accessible testing systems. This review reports validation studies in oncology
      and infectious diseases that have demonstrated the benefits of such approach in
      well-defined subpopulations of patients, moving the field from the drug
      development process toward clinical practice and routine application.
      Theragnostics may change the usual business model of pharmaceutical companies
      from the classic blockbuster model toward targeted therapies.

PMID- 19104226
TI  - New designs for clinical trials.
AB  - The pressures of ethics and equity on clinical trials have always been severe.
      The highest level of evidence about the usefulness of therapy is that obtained
      from well-planned, carefully conducted randomized, and where possible, double
      blind clinical trials. Traditional frequentist statistics have been used
      predominantly, but a Bayesian approach may offer more flexibility by leveraging
      more information from the results of a clinical trial. Innovative designs can
      minimize the number of patients included in a trial and decrease the chance of
      maintaining a patient in an unfavorable treatment arm.

PMID- 19104227
TI  - Deferred proxy consent in emergency critical care research: ethically valid and
      practically feasible.
AB  - Important ethical aspects apply to the process of obtaining consent in emergency
      critical care research: the incapacity of almost all patients for giving informed
      consent and the emergency and life-threatening nature of the conditions involved,
      resulting in short therapeutic time frames. We argue that deferred proxy consent
      is the preferable substitute for informed patient consent in emergency critical
      care research. However, researchers can face two problems when using this consent
      procedure. First, can proxies give a valid judgment for consent or refusal in the
      acute phase of the life-threatening illness of their relative, and second, what
      should researchers do with already obtained data when study procedures are
      finished (e.g., because the patient has died) before proxies can be informed and
      consent be sought? We propose approaching the relatives with information about
      the trial and asking them for consent only if it is ethically valid to do so. The
      first psychological distress may prohibit a complete understanding of the
      information, which is necessary for a true and valid informed proxy consent. In
      addition, we recommend using the study data if study procedures are finished
      before proxies can be informed and consent be sought, provided sufficient privacy
      measures have been applied.

PMID- 19104228
TI  - The design and interpretation of pilot trials in clinical research in critical
      care.
AB  - BACKGROUND: Pilot trials are important to ensure that large randomized trials are
      rigorous, feasible, and economically justifiable. The objective of this review is
      to highlight the importance of randomized pilot trials and to describe key
      features of their design and interpretation using examples from critical care.
      METHODS: We searched MEDLINE (1997-2007) and contacted experts to identify pilot
      randomized trials to exemplify and summarize their key methodologic features
      including objectives, sample size determination, outcomes, analysis, and
      reporting. RESULTS: Pilot trials can have distinct and broad objectives.
      Investigators can predefine explicit criteria for determining their success.
      Surrogate outcome analyses are common in pilot trials, yet are usually
      underpowered to detect meaningful differences in clinically important end points
      and thus, should be cautiously interpreted. Pilot trials can facilitate
      successful conduct of large clinical trials by informing study design and
      streamlining protocol implementation. RECOMMENDATIONS: We recommend that
      investigators define suitable objectives, determine sample size estimates, and
      select outcomes that will address their specific pilot trial objectives. Clinical
      effects documented in pilot trials should be reported with caution to avoid undue
      enthusiasm or pessimism about unstable estimates. Further methodologic work is
      required to identify optimal pilot trial design, indexing, and reporting.

PMID- 19104229
TI  - Logistics of large international trials: the good, the bad, and the ugly.
AB  - The pace of development in intensive care medicine seems to be increasing all the
      time. Nowhere is that more apparent than in the field of clinical trials. Large
      international multicenter studies are increasingly being used to evaluate new
      interventions and to provide epidemiologic data. Such studies promise fast
      results with good generalizability, but the limitations of these trials should
      not be forgotten in our search for a speedy conclusion. In this article we will
      discuss the good, the bad, and the potentially ugly side of international
      clinical trials in intensive care.

PMID- 19104230
TI  - Better conduct of clinical trials: the control group in critical care trials.
AB  - OBJECTIVE: To review trial design issues related to control groups. DESIGN:
      Review of the literature with specific reference to critical care trials. MAIN
      RESULTS AND CONCLUSIONS: Performing randomized controlled trials in the critical
      care setting presents specific problems: studies include patients with rapidly
      lethal conditions, the majority of intensive care patients suffer from syndromes
      rather than from well-definable diseases, the severity of such syndromes cannot
      be precisely assessed, and the treatment consists of interacting therapies.
      Interactions between physiology, pathophysiology, and therapies are at best
      marginally understood and may have a major impact on study design and
      interpretation of results. Selection of the right control group is crucial for
      the interpretation and clinical implementation of results. Studies comparing new
      interventions with current ones or different levels of current treatments have
      the problem of the necessity of defining "usual care." Usual care controls
      without any constraints typically include substantial heterogeneity. Constraints
      in the usual therapy may help to reduce some variation. Inclusion of unrestricted
      usual care groups may help to enhance safety. Practice misalignment is a novel
      problem in which patients receive a treatment that is the direct opposite of
      usual care, and occurs when fixed-dose interventions are used in situations where
      care is normally titrated. Practice misalignment should be considered in the
      design and interpretation of studies on titrated therapies.

PMID- 19104231
TI  - Clinical trials in the out-of-hospital setting: rationale and strategies for
      successful implementation.
AB  - Cardiopulmonary arrest and trauma are two of the major epidemics of our time. In
      most cases, the final outcome is altered, for better or for worse, by how
      interventions are provided in the prehospital setting, making that venue critical
      for lifesaving community research efforts. In certain venues, out-of-hospital
      emergency medical services personnel are highly skilled at managing
      resuscitations and routinely operate under strict, highly scrutinized protocols,
      resulting in extraordinary study compliance. Larger patient enrollment derived
      from population-based investigations can lead to faster study completion, less
      selection bias, higher-powered data, and enhanced subgroup analysis. Most
      importantly, the concomitant training, expert protocol development, and rigid
      scrutiny all lead to improved patient outcomes, regardless of study intervention.
      For successful implementation, emergency medical services personnel should be
      involved in study design, and utilize routine, automated data collection.
      Technologies should be provided that simplify tasks and diminish confounding
      variables. Considering that exception to informed consent is a critical
      component, prospective education and involvement of the medical community,
      community leaders, employee groups and the media, long before protocol
      implementation, is essential. Such efforts should be led by respected,
      academically authoritative, grassroots emergency medical services medical
      directors and trauma chiefs, preferably those based at the main trauma centers or
      public receiving facilities.

PMID- 19104233
TI  - Endocrinology of male puberty.
AB  - PURPOSE OF REVIEW: To review recent information leading to a better understanding
      of the endocrinology of male puberty, including information from earlier stages
      of life. RECENT FINDINGS: Differences in relative levels of luteinizing hormone
      (LH) and follicle-stimulating hormone (FSH) in the neonatal period have been
      further described, as well as changes in inhibin B and anti-Mullerian hormone
      levels. Studies among men with congenital hypogonadotropic hypogonadism suggest a
      role for the 'minipuberty of infancy' in inhibin B levels. Gonadotropin-releasing
      hormone analog-stimulated LH levels at the age of puberty may be useful in
      diagnosing hypogonadotropic hypogonadism. Inhibin B levels are likewise useful in
      monitoring spermatogenic activity. SUMMARY: Data from fetal life (men born small
      for gestational age with evidence of a defect in steroidogenesis, relatively high
      LH:FSH ratio among very premature boys), neonatal period (attenuated rise of
      inhibin B after rFSH stimulation among men with congenital hypogonadotropic
      hypogonadism), and puberty (often demonstrable by LH levels alone, progressive
      rise of insulin-like factor 3 levels, and decrease of anti-Mullerian hormone
      levels as a consequence of FSH and LH stimulation), all enhance the understanding
      of the physiology of puberty.

PMID- 19104234
TI  - What controls the timing of puberty? An update on progress from genetic
      investigation.
AB  - PURPOSE OF REVIEW: Puberty is an important developmental stage during which
      reproductive capacity is attained. Genetic and environmental factors both
      influence the timing of puberty, which varies greatly among individuals. However,
      although genetic variation is known to influence the normal spectrum of pubertal
      timing, the specific genes involved remain unknown. RECENT FINDINGS: Recent
      genetic analyses have identified a number of genes responsible for rare disorders
      of pubertal timing such as hypogonadotropic hypogonadism and Kallmann syndrome.
      However, although the genetic basis of population variation in the timing of
      puberty is an active area of investigation, no genetic loci have been
      reproducibly associated with pubertal timing thus far. SUMMARY: This review
      provides an update of the genes implicated in disorders of puberty, discusses
      genes and pathways that may be involved in the timing of normal puberty, and
      suggests additional avenues of investigation to identify genetic regulators of
      puberty in the general population.

PMID- 19104235
TI  - Treatment of central precocious puberty.
AB  - PURPOSE OF REVIEW: In consideration of the large number of the rapid advances in
      this area, it seems appropriate to highlight some of the recent studies that
      address factors involved in the decision to treat a child with central precocious
      puberty, and two recent advances in drug therapy. RECENT FINDINGS: There are
      still many areas of uncertainty regarding treatment of central precocious
      puberty, including the hormonal test results that support the diagnosis, the best
      way to predict adult height, and the effect of the age of the child on the amount
      of height gained during treatment (adult height minus predicted height). Many
      studies show that children with onset of symptoms before age 6 benefit the most,
      but a recent study showed no difference in height benefit between girls initially
      seen at at least 7 or more than 7 years. Two reports indicate that greater delay
      from the onset of puberty to the start of therapy with gonadotropin-releasing
      hormone analogue has a negative effect on adult height. Although there has been
      considerable experience with monthly injections of gonadotropin-releasing hormone
      analogues to suppress pubertal development, recent studies show that a slower
      released formulation given every 3 months is also effective in the majority of
      patients. The newest form of therapy involves a subcutaneous implant of the
      gonadotropin-releasing hormone analogue histrelin, which gives excellent
      gonadotropin suppression for 12 months. SUMMARY: Treatment of central precocious
      puberty continues to be a very active area of clinical investigation, but there
      are still unresolved questions that future studies will need to address.

PMID- 19104236
TI  - Adolescent obesity and bariatric surgery.
AB  - PURPOSE OF REVIEW: Examines the effects of bariatric surgery on adolescent
      obesity. RECENT FINDINGS: The risks and outcomes of bariatric surgery in
      adolescence are presently being defined and may be somewhat different from those
      in adults. Adolescents may have a greater risk of weight regain, and greater risk
      of noncompliance to treatment after surgery. However, long-term outcomes are not
      yet available, and the underlying metabolic benefits appear to be substantial and
      similar to those of adults. SUMMARY: Morbid obesity in adolescents has severe
      acute and chronic complications. Bariatric surgery in adolescents seems as well
      tolerated as in adults when performed in centers with appropriate experience and
      adequate surgical volume. The pathophysiologic implications of bariatric surgery
      are profound. A better understanding of the mechanisms leading to postsurgical
      improvement in insulin resistance and weight loss could lead to the development
      of other therapies to achieve the same effects with lesser morbidities.

PMID- 19104237
TI  - Gastrointestinal regulatory peptides.

PMID- 19104238
TI  - Substance P, obesity, and gut inflammation.
AB  - PURPOSE OF REVIEW: The purpose of this review is to present recent data on the
      effects of substance P on the development of two common pathological conditions,
      namely obesity and gut inflammation, and elucidate the role of this neuropeptide
      as a potential regulator between increased adiposity and exacerbated inflammatory
      responses during inflammatory bowel disease. RECENT FINDINGS: We present data
      that demonstrate a role for substance P in both obesity and inflammatory bowel
      disease and investigate potential effects on fat tissue that may influence the
      progression of intestinal inflammation. More specifically, we discuss new
      evidence for direct effects of substance P on fat tissue that determine fat depot
      size and overall weight in mice and analyze some of the potential mechanisms.
      Furthermore, we present data that describe changes in the intestinal sensory
      innervation, in particular substance P-positive innervation, during gut
      inflammation and new direct evidence of the effects of preestablished obesity in
      the outcome of experimental inflammation of the colon in mice. In the end we
      propose a link between the role of substance P in the promotion of obesity and
      the potential consequences on inflammatory bowel disease. SUMMARY: We propose
      that substance P may promote fat tissue expansion either centrally or
      peripherally and thus create a proinflammatory environment (as is the case with
      obesity) which may in turn affect the progression (exacerbate) of gut
      inflammation. Further studies are required on the effects of 'creeping fat' in
      inflammatory bowel disease in order to decipher the role of this type of fat
      depot expansion in the development of the disease.

PMID- 19104239
TI  - Sonic hedgehog in gastric physiology and neoplastic transformation: friend or
      foe?
AB  - PURPOSE OF REVIEW: To understand the role of sonic hedgehog (Shh) in normal
      gastric physiology and neoplastic transformation. RECENT FINDINGS: Emerging
      evidence shows that gastric epithelial cells produce Shh ligand, which
      subsequently targets the mesenchyme. This paracrine signaling event is
      recapitulated by Shh-producing tumors that signal to the supporting stroma to
      encourage growth. Primary cilia contain components of the hedgehog signaling
      apparatus, and thus are typically found on responding stromal cells. SUMMARY: In
      the stomach, Shh is produced in epithelial cells and received by responding cells
      in the mesenchyme. In vitro, Shh enhances gastric acid secretion and induces
      mucin expression. It remains to be determined whether the canonical signaling
      pathway mediates the observed epithelial effects. Shh expression and signaling is
      reduced in chronic gastritis, and Shh(-/-) embryos exhibit hyperplasia and
      metaplastic changes in the gastric mucosa. After its loss in the corpus, Shh is
      re-expressed in some gastric carcinomas typically arising in the distal stomach
      or antrum, suggesting that it promotes tumor growth.

PMID- 19104241
TI  - Current Opinion in Endocrinology, Diabetes & Obesity. Current world literature.

PMID- 19104240
TI  - Peptide processing and biology in human disease.
AB  - PURPOSE OF REVIEW: To describe recent advances in the processing of
      gastrointestinal hormones, and the consequences for human disease of mutations in
      the enzymes involved. RECENT FINDINGS: Although gastrointestinal prohormones were
      long regarded as devoid of biological activity, recent data indicate that the
      prohormones for both gastrin and gastrin-releasing peptide are bioactive, through
      different receptors from the mature hormones. Mutations in the family of
      prohormone convertases responsible for the initial steps in the processing of
      gastrointestinal hormones are associated with several different
      pathophysiological conditions in humans. SUMMARY: Human mutational studies, when
      taken together with the phenotypes observed in mice deficient in the prohormone
      convertases, emphasize the crucial importance of the processing enzymes in
      mammalian biology. Although the phenotypes may often be ascribed to defective
      production of a mature hormone or growth factor, the recognition that the
      precursors are independently bioactive suggests that the increased precursor
      concentrations may also contribute to the symptoms. The observation that the
      precursors often act through different receptors from the mature hormones may
      permit the development of precursor-selective antagonists for therapeutic use.

PMID- 19104242
TI  - Myocardial infarction in women: promoting symptom recognition, early diagnosis,
      and risk assessment.
AB  - Even with national campaigns to help increase awareness, most people do not
      realize that heart disease is now the leading cause of death for women. Women
      experiencing an acute cardiac event often do not recognize the symptoms or are
      misdiagnosed by healthcare providers because of atypical symptom presentation.
      This can lead to a significant delay in treatment and a less desirable recovery
      outcome. To help promote early identification of cardiac risk and cardiac events,
      this article highlights the range of symptom presentation in women with
      myocardial infarction and focuses on how advanced clinical nurses can increase
      nurses' and the public's understanding of this disease in women.

PMID- 19104244
TI  - The Emergency Severity Index 5-level triage system.
AB  - The Emergency Severity Index triage system is a relatively new 5-level mode of
      operations created in the late 1990s. This system provides an operational model
      to meet the needs of all patients. This triage process segregates patients into 5
      different treatment levels based on a variety of characteristics. This article
      discusses the Emergency Severity Index, how it works, its advantages and
      disadvantages, and implications for emergency department nurses.

PMID- 19104246
TI  - A comfortable place to say goodbye.
AB  - No death is easy, but we hope to die peacefully, with our loved ones surrounding
      us, comforted by each other's presence and the knowledge that the right decision
      has been made. The nurse's actions in the intensive care unit setting can promote
      hope for a comfortable place to say goodbye for the patient and his/her loved
      ones and the nursing staff and physicians. When nurses make the intensive care
      unit a comfortable place for the dying patients and their loved ones, we also
      make the patients' deaths comfortable for us. The problems encountered in
      implementing end-of-life care are explored in this article, as well as strategies
      to instill hope in families.

PMID- 19104247
TI  - Empowering family members in end-of-life care decision making in the intensive
      care unit.
AB  - Critical care nurses are often faced with working with families during the end-of
      life care of a loved one. Often there is indecisiveness in family members of
      critically ill patients when faced with making these difficult decisions. The
      purpose of this manuscript is to describe origins of indecisiveness in family
      members of critically ill patients who are faced with end-of-life care decisions.
      Strategies to empower family members during this crucial time are also discussed.

PMID- 19104248
TI  - Innovative solutions: providing specialized nursing care to the patient with
      acute neurologic injury in a general critical care unit.
AB  - A general critical care unit at a community hospital in the Midwest sought to
      improve care delivery to patients with acute neurologic injury. Nurses passionate
      about caring for this patient population were identified. Work groups established
      a plan and goals for improving care. Goals include standardized education for
      group members, standards of practice and policy development and revision, and
      equipment review and upgrading. This article reports on the results of this
      innovative strategy.

PMID- 19104249
TI  - Staff nurses' experiences of a change in the care delivery model: a qualitative
      analysis.
AB  - This qualitative study describes the staff nurses' perspective of change in the
      care delivery model and skill mix in an intermediate care unit. Data were
      collected in interviews in focus groups with the registered nurses affected by
      the change. Two major themes emerged: (1) autonomy and control and (2)
      interdependence. The nurses emphasized an increased satisfaction (self and
      patient) with this model. This study confirmed that autonomy, control, connection
      with the patient, and peer and interdisciplinary support and respect are
      important for the staff nurse. These findings reinforced the value of involving
      the staff members in change and the importance of giving voice to their
      perspective through qualitative research.

PMID- 19104257
TI  - Medication errors.

PMID- 19104252
TI  - A brief report of basic science: the effects of preincisional low-dose ketamine
      on natural killer cell activity in male Fischer 344 rats after intra-abdominal
      surgery.
AB  - Although the first line of defense in cancer treatment often is surgery, studies
      suggest that postoperative pain and anesthetic drugs suppress the activity of
      cells that lyse metastatic cells, that is, natural killer cells. We assessed the
      affect of low-dose ketamine on natural killer cell activity. The findings are
      presented in this brief report.

PMID- 19104260
TI  - Implant vendors and hospitals: competing influences over product choice by
      orthopedic surgeons.
AB  - BACKGROUND: Vendors of hip and knee implants court orthopedic surgeons to adopt
      their products. Hospitals, which have to pay for these products, now court the
      same surgeons to help reduce the number of vendors and contain implant costs.
      PURPOSES: This study measures the surgeon's perceived alignment of interests with
      both vendors and hospitals and gauges surgeons' exposure and receptivity to
      hospital cost-containment efforts. METHODOLOGY/APPROACH: We surveyed all
      practicing orthopedists performing 12 or more implant procedures annually in
      Pennsylvania. The survey identified the surgeon's preferred vendor, tenure with
      that vendor, use of the vendor during residency training, receipt of financial
      payments from the vendor, alignment of interests with both vendor and hospital
      stakeholders, and exposure and receptivity to hospital cost-containment efforts.
      FINDINGS: Surgeons have long-standing relationships with implant vendors, but
      only a small proportion receive financial payments. Surgeons align most closely
      with the vendor's sales representative and least closely with the hospital's
      purchasing manager. Paradoxically, surgeons support hospital efforts to limit the
      number of vendors but report that their own choice of vendor is not constrained.
      The major drivers of surgeons' alignment and stance toward cost containment are
      their tenure with and receipt of financial payments from the vendor. PRACTICE
      IMPLICATIONS: Hospitals face a competitive disadvantage in capturing the
      attention of orthopedists, compared with implant vendors. The vendors' advantage
      stems from historical, financial, and service benefits offered to surgeons.
      Hospital executives now seek to offer comparable benefits to surgeons.

PMID- 19104261
TI  - Quality and strength of patient safety climate on medical-surgical units.
AB  - BACKGROUND: Describing the safety climate in hospitals is an important first step
      in creating work environments where safety is a priority. Yet, little is known
      about the patient safety climate on medical-surgical units. PURPOSES: Study
      purposes were to describe quality and strength of the patient safety climate on
      medical-surgical units and explore hospital and unit characteristics associated
      with this climate. METHODOLOGY: Data came from a larger organizational study to
      investigate hospital and unit characteristics associated with organizational,
      nurse, and patient outcomes. The sample for this study was 3,689 RNs on 286
      medical-surgical units in 146 hospitals. FINDINGS: Nursing workgroup and
      managerial commitment to safety were the two most strongly positive attributes of
      the patient safety climate. However, issues surrounding the balance between job
      duties and safety compliance and nurses' reluctance to reveal errors continue to
      be problematic. Nurses in Magnet hospitals were more likely to communicate about
      errors and participate in error-related problem solving. Nurses on smaller units
      and units with lower work complexity reported greater safety compliance and were
      more likely to communicate about and reveal errors. Nurses on smaller units also
      reported greater commitment to patient safety and participation in error-related
      problem solving. PRACTICE IMPLICATIONS: Nursing workgroup commitment to safety is
      a valuable resource that can be leveraged to promote a sense of personal
      responsibility for and shared ownership of patient safety. Managers can
      capitalize on this commitment by promoting a work environment in which control
      over nursing practice and active participation in unit decisions are encouraged
      and by developing channels of communication that increase staff nurse involvement
      in identifying patient safety issues, prioritizing unit-level safety goals, and
      resolving day-to-day operational problems the have the potential to jeopardize
      patient safety.

PMID- 19104262
TI  - Assessing the performance of surgical teams.
AB  - BACKGROUND: High-performing and high-reliability teams are an important component
      of service delivery. With a focused emphasis on safety in acute care hospitals,
      understanding the nature of surgical teams and team performance is an essential
      component to achieving high-quality surgical care. More information is needed
      about the challenges to effective team functioning in the operating room, the
      influence of working conditions, and the environmental context on surgical team
      performance. PURPOSE: The purpose of this study is to describe the nature of
      surgical teams and how they perform in the operating room to contribute to a
      broader knowledge about high-performing and high-reliability teams in health care
      settings. METHODOLOGY/APPROACH: We conducted a qualitative study involving direct
      observation and semistructured interviews. Field observations of 10 high
      complexity surgeries and face-to-face interviews with 26 members of surgical
      teams were completed at one university medical center. A conceptual framework
      derived from the literature was developed to guide the selection of surgeries and
      surgical teams to be observed. Data were transcribed and analyzed to identify the
      factors and different conditions that influence the performance of these surgical
      teams. FINDINGS: The type of coordination and the degree of independent and
      interdependent coordination vary among the seven observed stages of the surgical
      process. Most of the surgical teams were ad hoc teams and as such, further
      challenged by consistently frequent "hand-offs" for break relief. Additional role
      demands influence the situational dynamics which can alter the adaptive capacity
      of the team. PRACTICE IMPLICATIONS: The surgical event evokes a changing degree
      of coordination and adaptation to complexity and uncertainty. In such
      environments, relational coordination through leadership can contribute to a
      successful surgical result, improvement of the overall process, including error
      reduction, and enhanced knowledge creation and dissemination, particularly
      germane in research university teaching hospitals.

PMID- 19104263
TI  - Building capacity for a transformation initiative: system redesign at Denver
      Health.
AB  - BACKGROUND: This article examines the development of transformation initiatives
      deliberate attempts to achieve systemic changes and rapid performance
      improvements. Accounts of transformation initiatives often reveal little about
      past organizational and contextual conditions that contributed to success.
      Instead, these accounts concentrate on change barriers. PURPOSE: We seek to
      restore balance to this field by examining how antecedent system capacities
      contributed to a successful transformation initiative. METHODOLOGY: This article
      presents a case study of the first 2 years of a system redesign initiative at an
      integrated safety-net health system and provides a historical analysis of
      developments during the decade preceding the redesign. FINDINGS: Beginning in the
      mid-1990 s, Denver Health benefited from strong municipal support for its
      development and expansion. Gradually, it developed its financial and human
      resources, organizational structure, change strategy, change-management
      capabilities, information technology, and physical plant. These antecedent
      capacities all contributed to the implementation of the 2004 system redesign and
      helped Denver Health overcome several constraints. IMPLICATIONS: Transformation
      initiatives may build on existing features and resources, even as they overcome
      or depart from others. The Denver Health case study helps researchers identify
      positive antecedents to transformation initiatives, assess the success of such
      initiatives in terms of implementation progress and outcomes, and recognize
      complementary contributions of incremental and episodic changes. The study alerts
      practitioners to the importance of assuring that change efforts rest on solid
      organizational foundations.

PMID- 19104264
TI  - Hospital innovativeness and organizational performance: evidence from English
      public acute care.
AB  - BACKGROUND: Hospitals around the world dedicate increasing attention and
      resources to innovation. However, surprisingly little is known about the nature
      of hospital innovativeness and its relationship with organizational performance.
      Given both the specific characteristics of the hospital sector and the rather
      mixed evidence from other industries, a positive innovation-performance link
      should not be taken for granted but requires empirical examination. PURPOSES: The
      purposes of this study were to introduce a perspective of hospitals as vital
      generators of innovation, to unpack the concept of innovativeness, to propose a
      measurement model for hospital innovativeness, and to empirically investigate the
      innovativeness-performance relationship. METHODOLOGY: We conducted a large-scale
      empirical study among the entire population of public hospital organizations that
      are part of the English National Health Service (n = 173) and analyzed the data
      using exploratory factor and regression analyses. FINDINGS: Our analyses suggest
      a significant positive relationship between science- and practice-based
      innovativeness and clinical performance but provide less unambiguous support for
      the existence of such a relationship between innovativeness and administrative
      performance. In particular, we find that higher levels of innovativeness are
      rather associated with superior quality of care than with measurable bottom-line
      financial benefits. PRACTICE IMPLICATIONS: Hospitals investing in innovation
      generating activities might find their efforts well rewarded in terms of tangible
      clinical performance improvements. However, to achieve measurable financial
      benefits, numerous hospitals have yet to discover and capture the commercial
      value of some of their innovations-a challenging task that requires a holistic
      innovation management and an effective network of complementary partners.

PMID- 19104265
TI  - Intrasectoral variation in mission and values: the case of the Catholic health
      systems.
AB  - BACKGROUND: Catholic health systems represent a unique sector of nonprofit health
      care delivery organizations because they must be accountable to institutional
      pressures of the Roman Catholic Church, in addition to responsiveness to market
      pressures. Mission statements and values are purported to be the driving force of
      Catholic institutional identity. Central to the understanding of the Catholic
      health care delivery sector is the exploration of variation in mission and values
      statements across the homogeneous field of organizations. PURPOSES: The purposes
      of this study were to identify expressed organizational identity variation-in
      terms of keywords in mission statements and values-of Catholic health systems in
      the United States by applying a methodology that integrates text and social
      network analytical techniques. METHODOLOGY: Data were obtained from the Web site
      of The Catholic Health Association of the United States and the Web sites of 50
      Catholic health systems in 2007. Catholic health system mission statements and
      values were assessed using a cross-sectional study design. Text analysis and
      social network techniques were employed to identify the most central words in the
      texts and linkages among mission statement components and values. FINDINGS: This
      study identifies the components of a common mission statement and the most shared
      and unique values for a Catholic health system. Even with tremendous similarity,
      there is also evidence of intrasectoral variation between Catholic health system
      keywords in mission statements and values. PRACTICE IMPLICATIONS: Management
      implications include the consideration of word relationships developing and
      constructing mission and values statements to form the framework for strategic
      vision and management decision making, to assess potential partnership
      arrangements based on expressed mission statements and values, and to use in
      executing due diligence in mergers and partnerships.

PMID- 19104266
TI  - The internal processes and behavioral dynamics of hospital boards: an exploration
      of differences between high- and low-performing hospitals.
AB  - BACKGROUND: Nonprofit hospital boards are under increasing pressure to improve
      financial, clinical, and charitable and community benefit performance. Most
      research on board effectiveness focuses on variables measuring board structure
      and attributes associated with competing ideal models of board roles. However,
      the results do not provide clear evidence that one role is superior to another
      and suggest that in practice boards pursue hybrid roles. Board dynamics and
      processes have received less attention from researchers, but emerging theoretical
      frameworks highlight them as key to effective corporate governance. PURPOSE: We
      explored differences in board processes and behavioral dynamics between
      financially high- and low-performing hospitals, with the goal of developing a
      better understanding of the best board practices in nonprofit hospitals.
      METHODOLOGY/APPROACH: A comparative case study approach allowed for in-depth,
      qualitative assessments of how the internal workings of boards differ between low
      and high-performing facilities. FINDINGS: Boards of hospitals with strong
      financial performance exhibited behavioral dynamics and internal processes that
      differed in important ways from those of hospitals with poor financial
      performance. PRACTICE IMPLICATIONS: Boards need to actively attend to key
      processes and foster positive group dynamics in decision making to be more
      effective in governing hospitals.

PMID- 19104268
TI  - Depression, alcohol abuse, and healthy living strategies.

PMID- 19104267
TI  - A national view of workplace injuries in nursing homes.
AB  - OBJECTIVES: Data from a large sample of nursing homes were used to examine the
      cross-sectional association between workplace injuries and organizational
      factors, caregiver staffing levels, and quality. METHODS: Three sources of data
      were used, the Occupational Safety and Health Administration data initiative for
      2004, the Online Survey Certification and Recording system representing 2004, and
      the 2004 Area Resource File. RESULTS: For the organizational characteristics of
      interest, the results show that for-profit facilities were less likely to report
      high injury rates and that facilities with a higher average occupancy and
      belonging to a chain were more likely to report high injury rates. For the
      staffing characteristics of interest, facilities with high staffing levels of
      registered nurses were more likely to report high injury rates, whereas those
      with high staffing levels of nurse aides were less likely to report high injury
      rates. For the quality characteristic of interest, facilities of low quality (as
      measured by quality-of-care deficiency citations) were more likely to report high
      injury rates. CONCLUSIONS: Workplace injuries are associated with organizational,
      caregiver, and quality characteristics of nursing homes. This may present an
      opportunity to reduce high injury rates.

PMID- 19104269
TI  - Addressing cultural heterogeneity among Hispanic subgroups by using Campinha
      Bacote's model of cultural competency.
AB  - Campinha-Bacote's model "The Process of Cultural Competence in Delivery of Health
      Care Services" is used to describe Hispanic cultural heterogeneity and to guide
      nurses in providing culturally competent and sensitive holistic care to
      individuals from different Hispanic subgroups. But for nurses to do so,
      healthcare organizations also must make the appropriate resources and structural
      supports available to them.

PMID- 19104271
TI  - The global economic meltdown and holistic interventions for depression.

PMID- 19104272
TI  - The effects of employer-provided massage therapy on job satisfaction, workplace
      stress, and pain and discomfort.
AB  - Long-term care staff have high levels of musculoskeletal concerns. This research
      provided a pilot program to evaluate the efficacy of employer-funded on-site
      massage therapy on job satisfaction, workplace stress, pain, and discomfort.
      Twenty-minute massage therapy sessions were provided. Evaluation demonstrated
      possible improvements in job satisfaction, with initial benefits in pain
      severity, and the greatest benefit for individuals with preexisting symptoms. A
      long-term effect was not demonstrated.

PMID- 19104273
TI  - Smoking and pregnancy: reconciling incompatibilities.

PMID- 19104274
TI  - Opening new doors: RN to BSN students' experiences in a holistic nursing course.
AB  - A phenomenological study was conducted to investigate RN to BSN students'
      experiences in a holistic nursing course. A purposive sample of 19 RN to BSN
      graduates participated. Five theme clusters emerged when the formulated meanings
      were organized into categories: (1) uncertain beginnings, (2) shifting
      perspectives and power, (3) ripples of caring, (4) seeing the body, mind, spirit
      connection, and (5) from everyday practice to caring praxis. Findings provide
      evidence of the power of holistic nursing education to facilitate personal
      development and enhance professional practice.

PMID- 19104275
TI  - Over time: reflections after a myocardial infarction.
AB  - Self-care is especially important after a heart attack when daily lifestyle
      changes are needed. Performance of self-care behaviors after a myocardial
      infarction assists individuals in minimizing the progression of coronary heart
      disease. Uncovering patients' reflections after myocardial infarction provides a
      therapeutic window to target self-care interventions.

PMID- 19104276
TI  - Lavandula angustifolia Miller: English lavender.
AB  - Folk and traditional therapeutic use of the essential oil of English lavender for
      pain, infection, relaxation, and sedation dates back centuries. Current research
      focusing on the inherent synergism of Lavandula angustifolia Miller demonstrates
      great potential for future applications. Today's investigations may provide the
      key to eradicating degenerative inflammatory disease, infectious disease, and
      carcinogenesis.

PMID- 19104278
TI  - Do shoes matter? A story of shoes in the neonatal intensive care unit.
AB  - Faced with an increase in foot-related absences and complaints of foot pain by
      staff, a nurse manager sought help from the nursing research department staff to
      help find answers to this problem. The authors discuss how replacing the shoes
      that the nurses wore to a walker-style shoe was able to improve not only the foot
      pain but also the unit's health as well.

PMID- 19104277
TI  - Integrative therapeutic considerations in alcohol abuse.

PMID- 19104279
TI  - What can an intermediate care unit do for you?

PMID- 19104280
TI  - Responding to similarities and differences between Filipino and American nurses.

PMID- 19104281
TI  - Improving patient admissions with dedicated admission nurses.

PMID- 19104282
TI  - Organizational strategies to recruit clinical nurse specialists.
AB  - There is strong evidence of the value of the clinical nurse specialist (CNS) role
      in the acute care environment. Individual hospitals may encounter barriers in
      recruiting qualified CNSs. The authors discuss one organization's journey to
      increase recruitment of CNSs through the implementation of a service-line
      specific role and a formal staff development program. The number of CNSs in the
      organization increased with these interventions.

PMID- 19104283
TI  - A competency transcript to assess and personalize new graduate competency.
AB  - The competence of a new registered nurse (RN) at the time of graduation
      influences the rapidity with which the RN becomes an effective practitioner. One
      school of nursing offering a bachelor of science in nursing developed a
      competency documentation system, a "competency transcript," to better describe
      the graduate's clinical judgment and psychomotor skill. This transcript was used
      as a communication tool between a clinical agency and a university school of
      nursing and was also used to help one hospital personalize orientation based on
      the learning needs of the graduate, with the goal of decreasing orientation time
      and cost.

PMID- 19104284
TI  - Shared leadership: taking flight.
AB  - Nursing leaders are continually seeking ways to improve the work environment in
      their organizations. Instituting a shared leadership model supports a journey to
      promote a culture of nursing excellence. The author reviews key principles and
      how these principles were used as catalysts for change. Creation and
      implementation of the shared leadership model at the medical center have resulted
      in decreased nursing turnover, higher patient satisfaction scores, and enhanced
      patient outcomes.

PMID- 19104285
TI  - Case management delivery models: the impact of indirect care givers on
      organizational outcomes.
AB  - OBJECTIVE: This study examined the effect of 2 case management delivery models on
      the organizational outcomes of length of stay (LOS) and payment denials.
      BACKGROUND: Organizational leaders frequently identify case management as a
      method to manage LOS and demonstrate fiscal responsibility; yet, most case
      management research is anecdotal, describing specific patient populations or
      clinical units for outcome measurement. METHODS: Regression analyses and analyses
      of variance were used to examine the role functions of case managers and the
      impact on LOS and payment denials. Outcomes were evaluated on medical, surgical,
      neurology, and cardiology populations across general, intermediate, and intensive
      levels of care. RESULTS: Caseload distribution and role definition had a
      statistically significant impact on LOS and denial management across clinical
      specialty, units, and levels of care. The role of the case manager predicted 11%
      of the organizations LOS management. CONCLUSION: Case management role definition
      impacts organizational success measures found in LOS reduction and improved
      reimbursement. Although only 11% of the LOS was predicted by the role function of
      care coordinators, altering a single RN role had a statistically significant
      impact on LOS across clinical specialties and levels of care, demonstrating that
      indirect care givers have an important impact on organizational success.

PMID- 19104286
TI  - Non-value-added time: the million dollar nursing opportunity.
AB  - The dual crises of high healthcare costs and the nursing shortage require a
      better understanding of inpatient nursing unit activities and, more specifically,
      their costs and the drivers of inefficiencies. This includes knowing not only how
      staff spend their time but also how much of this time is non-value-added (NVA)
      because wasted time leads to both high costs and nurse dissatisfaction. The
      authors discuss a study that determined the NVA time and costs of acute care
      nursing unit staff, identified drivers of high-cost NVA time, and compared
      activities and costs by type of nursing unit. These data have considerable
      implications for developing efficient and effective nursing care delivery models
      and for implementing process improvement and staff satisfaction initiatives.

PMID- 19104287
TI  - From the editor.

PMID- 19104288
TI  - Making high-quality, patient-centered care a reality.
AB  - The Institute for Healthcare Improvement and others have spent a decade
      transforming the concept of patient-centered care from the realm of idea to the
      reality of practice. In this introduction, we provide a summary of this
      transformation, and the practical steps practices and health systems can take to
      make their transition to providing more patient-centered care.

PMID- 19104289
TI  - Making patient-centered care reliable.
AB  - Multiple reports have concluded that healthcare does not reliably meet patient
      needs and can even cause harm. The Institute for Healthcare Improvement (IHI) has
      adapted reliability principles and methods from other industries and applied them
      in healthcare with promising results in hospital settings. This article describes
      how one outpatient system successfully applied the IHI reliability methods to
      multiple clinical and administrative processes. How the application may differ in
      outpatient environments is also discussed. In particular, the patient role is
      much more central, and a strong collaborative engagement with the patient is
      likely necessary to achieve high reliability. Applying reliability principles to
      patient-centered processes is a critical and undeveloped area.

PMID- 19104290
TI  - Activation of patients for successful self-management.
AB  - Patients, not healthcare providers, are the primary managers of their health
      conditions. Current healthcare falls short of providing the kind of support that
      patients need to optimally manage their conditions. But there are simple and
      effective self-management support tools and methods that are easy to learn and
      can be used within the time constraints of the office visit. In addition to tools
      and methods, supporting self-management requires practice redesign to reliably
      deliver optimal care to all patients. Whether the care team consists of a solo
      physician or a large, multiphysician organization, applying basic principles and
      using simple tools can enable patients to take a more active role in improving
      their health.

PMID- 19104291
TI  - Transforming care teams to provide the best possible patient-centered,
      collaborative care.
AB  - Patient experience of care is now a crucial parameter in assessing the quality of
      healthcare delivered in the United States. Continuity, patient-driven access to
      care, and being "known" by a provider or practice, particularly for patients with
      chronic diseases, have been shown to enhance patient satisfaction with care and
      health outcomes. Healthcare systems are challenged to effectively meet the wants
      and needs of patients by tailoring interventions based on each person's unique
      set factors-his or her strengths, preferences, and personal and social context.
      Creating care teams, a coordinated multidisciplinary group of healthcare
      professionals, enables a practice to take advantage of the skill sets represented
      and redesign care delivery with the patient and community as the focal point.
      This article describes the attributes of highly functioning care teams, how to
      measure them, and guidance on creating them. A case example illustrates how these
      ideas work in practice.

PMID- 19104292
TI  - Accessing patient-centered care using the advanced access model.
AB  - Waits and delays for healthcare are legendary. These delays are not only
      frustrating and potentially hazardous for patients and providers but also
      represent significant cost to office practices. The traditional medical model
      that defines urgent care versus routine care is a vain and futile attempt to sort
      demand. This approach is at constant odds with patients' definition of urgency.
      Trusting patients to determine when and how they want to access care makes sense
      from a customer service perspective. If approached systematically using the
      principles of Advanced Access, patient demand patterns can be tracked to forecast
      demand. These demand patterns become the template for deploying the resources
      necessary to meet patients' needs. Although not a simple journey, the
      transformation to Advanced Access provides an entree to patient-centered care
      where patients can say, "I get exactly the care I want and need, when I want and
      need it."

PMID- 19104293
TI  - Balanced measures for patient-centered care.
AB  - The Institute for Healthcare Improvement has long supported the use of balanced
      measures to assess improvement among patients at both the individual and the
      population levels. Although biomedical outcomes and process measures have been
      widely accepted, patient-reported measures are still not in widespread use. The
      most common use of such measures is at the population level to gauge satisfaction
      with care long after it has been provided. This article examines barriers and
      solutions to including patient-reported measures at the point of care.

PMID- 19104294
TI  - CARE Vital Signs supports patient-centered, collaborative care.
AB  - CARE Vital Signs refers to a standard form created by practices to Check what
      matters to patients, Act on that assessment, Reinforce the actions, and
      systematically Engineer or incorporate actions into staff roles and clinical
      processes. On its face, CARE Vital Signs is a deceptively simple tool that, when
      properly used, can help a practice attain levels of efficiency and quality. This
      article describes the rationale for CARE Vital Signs and the ways it can be used
      for the greatest benefit.

PMID- 19104295
TI  - TROT line: live and direct from the republic of Texas.

PMID- 19104296
TI  - What if ...: You feel the way that a colleague speaks to or about patients is
      inappropriate?

PMID- 19104297
TI  - Complications following limb-threatening lower extremity trauma.
AB  - OBJECTIVE: Our objective is to report the nature and incidence of major
      complications after severe lower extremity trauma. DESIGN: Multicenter,
      prospective, observational study. SETTING: Eight level-1 trauma centers.
      PATIENTS/PARTICIPANTS: Five hundred forty-five patients were followed for 2
      years. INTERVENTION: Amputation or reconstruction. MAIN OUTCOME MEASUREMENTS: The
      type and number of complications associated with these injuries were recorded at
      baseline, 3-, 6-, 12-, and 24-month intervals. RESULTS: One hundred forty-nine
      underwent amputation during the initial hospitalization. The revision amputation
      rate was 5.4%. Among the amputation group, a complication was noted most
      frequently at 3 months (24.8%), and the most commonly seen complication was wound
      infection (34.2%). Wound complications including dehiscence (13.4%) were seen
      more commonly in the amputation group. Three hundred seventy-one limb
      reconstructions were performed with 25 patients (3.9%) requiring late amputation.
      The most frequently reported complication was at 6 months for the salvage group
      (37.7%), and the most commonly seen complication was wound infection (23.2%). Not
      surprisingly, osteomyelitis (8.6%) and nonunions (31%) were seen more commonly in
      the salvage group. Complications of wound infection, osteomyelitis, nonunion,
      malunion, and prominent hardware resulted in rehospitalization in at least one
      third of patients. However, patients who underwent reconstruction were more
      likely to be hospitalized for these complications. CONCLUSIONS: Patients with
      severe lower extremity injuries can expect a significant number of complications,
      most notably wound infection, nonunion, wound necrosis, and osteomyelitis. A
      large portion of these will require additional inpatient or operative treatment.
      Patients electing for reconstruction can expect a higher risk of complications.

PMID- 19104298
TI  - Computed tomography as a predictor of hip stability status in posterior wall
      fractures of the acetabulum.
AB  - OBJECTIVES: Studies using 2-dimensional computed tomography-derived criteria
      indicate that, in general, posterior wall fractures involving less than 20% of
      the posterior wall are stable and able to withstand physiologic loads, whereas
      those involving greater than 40%-50% are unstable, leaving a wide range of
      posterior wall fractures classified as indeterminate. The purpose of this study
      was to assess the ability of static measurement of posterior acetabular wall
      fragment size using computed tomography to predict hip stability status, as
      determined by dynamic stress examination under anesthesia. DESIGN: Diagnostic
      level I. Retrospective analysis with testing of previously developed diagnostic
      criteria in a series of consecutive patients (with universally applied reference
      "gold" standard). SETTING: Level I trauma center. PATIENTS: Thirty-three
      consecutive patients with isolated unilateral posterior wall (OTA 62-A1)
      acetabular fractures were evaluated by dynamic fluoroscopic stress testing under
      general anesthesia (examination under anesthesia) to determine hip stability
      status and subsequent clinical treatment. INTERVENTION: Three methods were used
      in a blinded fashion to calculate posterior wall fracture fragment size using 2
      dimensional computed tomograms. These methods include those previously described
      by Calkins et al, which measures the smallest amount of intact acetabular arc,
      and Keith et al, which measures fragment size at the level of the fovea, and an
      alternative modification of that of Keith et al using the level of largest
      posterior wall deficit. Each method classifies hip instability into 3 groups: (1)
      stable, (2) indeterminate, and (3) unstable. The examination under anesthesia
      served as the gold standard. MAIN OUTCOME MEASUREMENT: Examination under
      anesthesia RESULTS: Examination under anesthesia determined 15 hips to be
      unstable and 18 hips to be stable. The analyses showed that the methods of
      Calkins et al and Keith et al had a substantial percentage of incorrect
      predictions, especially in the critical group 1 patients (those predicted to be
      stable but were actually unstable). The percent incorrectly predicted for these
      group 1 patients was 33.3% (positive predictive value 66.7%) for the data derived
      form Calkins et al and 14.3% (positive predictive value 85.7%) for the data
      derived form Keith et al. In contradistinction, for the alternative method,
      specificity, sensitivity, and positive predictive value were all 100% with a 0%
      incorrectly predicted. However, with this alternative method, there was an
      increase in the number of group 2 fractures (23), as compared with the group 2
      numbers for Calkins et al (n = 7) and Keith et al (n = 18). Reanalysis of the
      data for better potential cut points indicated that none of the methods could be
      improved in this way. CONCLUSIONS: The alternative method is the only reliable
      technique that is predictive of hip stability for small fracture fragments while
      also being predictive of instability for large fracture fragments. However, these
      findings are based on small patient numbers, and there remain a substantial
      number of fractures involving 20% or more of the posterior wall that are both
      stable and unstable by examination under anesthesia. Therefore, given the low
      risk of the stress examination and the inherent problems making the computed
      tomography measurements, dynamic fluoroscopic stress testing under general
      anesthesia should be the preferred method for the determination of hip stability
      status after posterior wall fractures of the acetabulum.

PMID- 19104299
TI  - What constitutes a Young and Burgess lateral compression-I (OTA 61-B2) pelvic
      ring disruption? A description of computed tomography-based fracture anatomy and
      associated injuries.
AB  - OBJECTIVE: The objectives of this study were to provide computed tomography (CT)
      based description of the anatomic specifics of lateral compression (LC)-1 pelvic
      ring disruptions and to describe injury severity to other body systems and their
      correlation with fracture anatomy. DESIGN: Retrospective radiographic assessment
      and review of records SETTING: A level 1 trauma and tertiary referral center.
      PATIENTS/PARTICIPANTS: We identified a consecutive series of 100 patients with
      Young and Burgess LC-1 pelvic ring disruptions from the trauma registry database
      at a level 1 trauma center and evaluated their radiographs, CT scans, and injury
      and admission information. INTERVENTION: None. MAIN OUTCOME MEASUREMENTS:
      Presentation films were used to confirm injury type. The CT scan of the bony
      pelvis was reviewed for each patient by independent reviewers, with disagreement
      being resolved by the senior author. Sixteen categories were reviewed for each
      patient (rami fractures, segmental/comminuted rami fractures, Nakatani
      classification of rami fractures, anterior and posterior sacral fractures, and
      Denis classification). Sacral fractures were graded based on severity (0, no
      fracture; 1, buckle fracture; 2, simple fracture line; 3, comminuted fracture
      line). The age, Injury Severity Score (ISS), and 6 categories of Abbreviated
      Injury Scale (AIS) were recorded for each patient. A statistical analysis was
      performed to test the associations between fracture characteristics and injury
      severity. RESULTS: Our group had 54 women and 46 men. The mean age was 37.84 +/-
      1.95. All patients but 3 had 1 or more rami fractures, and all but 2 had a sacral
      fracture. Of the 116 superior rami fractures, Nakatani 3 was the most common type
      (60/116, 51.7%). Of the 217 rami fractures, 47 (21.7%) were segmental or
      comminuted. Of the 98 anterior sacral injuries, there were 9 (9.2%) buckle
      fractures, 39 (39.8%) simple fractures, and 50 (51.0%) comminuted fractures. Of
      these 98 anterior sacral injuries, 47 (48.0%) were complete, passing through the
      sacrum and exiting the posterior cortex. Increasing severity of anterior sacrum
      fracture was associated with the presence of a complete sacral fracture (P <
      0.0001). Of the 98 sacral fractures, 50 (50.0%) were Denis type 1, 41 (41.8%)
      Denis type II, and 7 (7.1%) Denis type III. Higher Denis types had higher
      likelihood of complete fractures of the sacrum (P < 0.0001). There was a
      significant association between the presence of a comminuted rami fracture and a
      complete sacrum injury (P = 0.003) and a trend to higher rates in Nakatani 2
      superior rami fractures (P = 0.169). There were 4 deaths due to trauma in this
      group, and the mean ISS score was 17.16 +/- 1.3. The highest mean system AIS
      score in these patients was extremity (2.42 +/- 0.06) followed by chest (1.28 +/-
      0.17) and abdomen (1.03 +/- 1.30). There was a trend to higher mean ISS scores (P
      = 0.2287) and significantly higher abdominal AIS scores (P = 0.0014) in those
      with a complete sacral fracture. Those with comminuted and complete sacral
      fractures were more likely to be symptomatic and require posterior ring
      stabilization (P = 0.003 and 0.043, respectively) CONCLUSIONS: LC-1 fractures of
      the pelvic ring represent a spectrum of injuries, with a large proportion having
      complete disruption of the sacrum. This complete injury of the sacrum is
      predicted by Denis type, severity of anterior ring disruption, abdominal AIS, and
      potentially location of rami fracture and ISS. CT scanning best defines these
      injuries.

PMID- 19104300
TI  - The treatment of intertrochanteric fractures: results using an intramedullary
      nail with integrated cephalocervical screws and linear compression.
AB  - OBJECTIVE: A new device for the treatment of intertrochanteric fractures that
      uses 2 cephalocervical screws in an integrated mechanism allowing linear
      intraoperative compression and rotational stability of the head/neck fragment has
      been developed. The aim of this study was to describe the results using this
      device for the treatment of stable and unstable intertrochanteric fractures.
      DESIGN: Prospective, consecutive. SETTING: Academic Trauma Center. METHODS:
      Between March 1, 2005, and July 31, 2006, 100 consecutive patients with an
      intertrochanteric fracture were treated with a new trochanteric antegrade nail
      (InterTan; Smith-Nephew, Memphis, TN). All living patients were followed up for a
      minimum of 1 year postoperatively (range 12-27 months). Clinical and radiographic
      examinations were performed until healing and at the 1-year anniversary of the
      index procedure. Healing, pain with ambulation, return to activities of daily
      living, the modified Harris hip score, and Barthel Index were used to evaluate
      outcomes. RESULTS: The mean age of the patients was 81.2 (+/-11.3) years. Thirty
      seven patients died, 12 were too infirmed for follow-up, and 3 could not be
      located, leaving 48 patients available for final evaluation. The average surgical
      time was 41 minutes (13-95 minutes). This rose significantly with the complexity
      of the fracture (OTA/AO classification: A1 versus A3, P = 0.016). All fractures
      healed within 16 weeks (range 10-16 weeks). Radiographic analysis at healing
      revealed no loss of reduction, no uncontrolled collapse of the neck, no
      nonunions, no femoral shaft fractures, and no implant failures. Two cases in the
      series were poorly reduced and settled into varus malalignment. There was no
      varus malposition seen in the remaining 46 fractures. The mean prefracture Harris
      hip score (75.1 +/- 13.4) was significantly reduced at the time of follow-up
      (70.3 +/- 14.5, P = 0.003); 58% of the patients recovered their prefracture
      status. No significant difference was seen for the Barthel Index. CONCLUSIONS:
      The InterTan device appears to be a reliable implant for the treatment of
      intertrochanteric femoral fractures. Its design provides for stability against
      rotation and minimizes neck malunions (shortening) through linear intraoperative
      compression of the head/neck segment to the shaft. As a result of the negligible
      complication rate and improved clinical outcomes, this implant is now the
      standard treatment for all intertrochanteric fractures at our institution.

PMID- 19104301
TI  - Biomechanical evaluation of extramedullary versus intramedullary fixation for
      reverse obliquity intertrochanteric fractures.
AB  - OBJECTIVES: This study evaluated the 135-degree hip screw, 95-degree hip screw,
      and intramedullary hip screw (IMHS) for fixation of reverse obliquity
      intertrochanteric fractures. METHODS: Twelve matched pairs of human femora (mean
      age 64 years) were obtained. Osteotomies were created in left femurs at a 33
      degree angle, running inferolaterally from the lesser trochanter to mimic reverse
      obliquity intertrochanteric fractures. Right femora acted as controls. Three
      groups of left femora (n = 4 per group) had a 135-degree hip screw, 95-degree hip
      screw, or IMHS inserted. Strain gages were placed distal to the fracture site to
      monitor fragment strain. A linearly variable differential transformer measured
      lateral displacement of the proximal femur. An Instron tester applied vertical
      loads to the femoral head. Outcome measures of stiffness, strain, and lateral
      displacement were determined at 25-degree adduction, 25-degree abduction, 25
      degree flexion, and 90-degree flexion. A 2-cm bone gap was then created at the
      fracture site to simulate comminution and the mechanical tests repeated. Failure
      load was assessed in 25-degree adduction with a bone gap. RESULTS: There was no
      difference in normalized stiffness between constructs before creation of a gap.
      After gap creation, stiffness of all constructs was reduced (P = 0.03), and there
      was a significant difference in adduction (135-degree hip screw, 46.6% +/- 3%; 95
      degree hip screw, 22.9% +/- 2%; and IMHS, 53.7% +/- 7.8%) (P < 0.05). Similar
      results were noted for abduction and flexion. There was no significant difference
      in lateral displacement between constructs before (P = 0.92) or after (P = 0.26)
      gap creation. Failure load was significantly different (135-degree hip screw,
      1222 +/- 560 N; 95-degree hip screw, 2566 +/- 283 N; and IMHS, 4644 +/- 518 N) (P
      = 0.02). CONCLUSIONS: With bone contact, there were no statistically significant
      differences in the stiffness between the constructs. With a gap, however, the
      IMHS bone implant construct was significantly stiffer and had a greater load to
      failure than the 135-degree and 95-degree constructs.

PMID- 19104302
TI  - Quality of life after a stable trochanteric fracture--a prospective cohort study
      on 148 patients.
AB  - OBJECTIVE: The aim of this study was to report the long-term outcome for patients
      with stable trochanteric fractures, especially regarding the health-related
      quality of life (HRQoL). DESIGN: A prospective cohort study with a 2-year follow
      up. SETTING: Four university hospitals. PATIENTS: One hundred forty-eight
      consecutive patients with stable trochanteric fractures, that is, a 2-part
      fracture (J-M 1 and 2) according to the Jensen-Michaelsen classification, treated
      with a sliding hip screw. MAIN OUTCOME MEASUREMENTS: Mortality rate, reoperation
      rate, pain at the hip, walking ability, activities of daily living (ADL)
      function, and HRQoL assessed with the EuroQol-5D (EQ-5D index score). RESULTS:
      The 2-year mortality rate was 29%. The reoperation rate was 3%. At the final
      follow-up, 81% of the patients reported no or only limited pain at the hip, 55%
      had regained their prefracture walking ability, and 66% their prefracture level
      of ADL function. The EQ-5D index score decreased from 0.69 before the fracture to
      0.57 at 4 months, 0.59 at 12 months, and 0.66 at 24 months. CONCLUSIONS: Besides
      the expected mortality rate, the results of the study confirm a low reoperation
      rate and a good outcome regarding pain at the hip and only limited deterioration
      in HRQoL after a stable trochanteric fracture. However, a considerable number of
      the patients experienced deterioration in their walking ability and ADL function.
      The data on HRQoL obtained in this study can be used in future healthcare
      evaluations and to calculate quality-adjusted life years.

PMID- 19104303
TI  - Incidence and morphology of the posteromedial fragment in bicondylar tibial
      plateau fractures.
AB  - OBJECTIVES: Bicondylar tibial plateau fractures featuring extensive articular
      involvement have a record of mixed clinical results. Recent discussion has
      focused on the significance of a posteromedial articular fragment in bicondylar
      injuries. This fragment has often gone unrecognized or has not been addressed.
      The posteromedial fragment is defined as any posteriorly based articular fracture
      of the medial plateau with the fracture line exiting the medial cortex. This
      study is designed to produce a detailed description of the incidence, size, and
      shape of this fracture, as this may be helpful in driving the choice of both
      approach and fixation for these injuries. Furthermore, a better understanding of
      this fracture's morphology may lead to a better ability to model the
      biomechanical reliability of laterally based locking fixation in securing the
      reduction of this fracture fragment. DESIGN: Retrospective study of patient
      records and computed tomography scans. SETTING: Level I university regional
      trauma center. PATIENTS: All patients treated for bicondylar tibial plateau
      fracture from January 1, 2002, through August 31, 2007. RESULTS: One hundred
      forty-eight patients were identified in the 5.5-year period, and 111 had complete
      computed tomography records (75%). Of 111 bicondylar tibial plateau fractures
      analyzed, this fragment occurred in 65 cases (59% incidence) and on average
      accounted for 25% of the total tibial plateau joint surface. There was greater
      than 5 mm of articular displacement in 55% of cases. The posteromedial fragment
      exhibits a vertical fracture pattern (average sagittal angle 73 degrees),
      suggestive of shear instability and vertical displacement. CONCLUSIONS: Given the
      high frequency, significant portion of the joint involved, significant
      displacement, and pattern suggestive of instability, surgeons need to be
      cognizant of this pattern and may need to consider directly reducing and fixating
      this fragment through a posteromedially based approach. Overall morphologic
      findings of the posteromedial fragment are highly consistent with other recent
      data on this pattern. This information may also be useful in modeling fracture
      fixation for future study.

PMID- 19104304
TI  - Nonunions treated with autologous preparation rich in growth factors.
AB  - OBJECTIVES: To evaluate the clinical safety and efficacy of using a biologic
      technology known as preparation rich in growth factors (PRGF) for the treatment
      of nonhypertrophic nonunion. DESIGN: The design of the study was a retrospective
      case series. SETTING: The private practice was in 2 centers. PATIENTS: There were
      15 patients with a total of 16 aseptic nonunions, 12 diaphyseal and 4
      supracondylar, diagnosed as nonhypertrophic. The mean time since prior surgical
      treatment was 21 months (9-46 months). INTERVENTION: Supracondylar and diaphyseal
      nonunions followed surgical fixation with condylar plating or intramedullary
      nailing, whereas a composite biomaterial created by mixing PRGF with bone
      allograft was applied. The area was then covered with autologous fibrin
      membranes. Stable nonunions were treated with repeated percutaneous injections of
      PRGF; this minimally invasive procedure was also applied if delayed healing was
      suspected after surgical treatment. MAIN OUTCOME MEASUREMENTS: Radiographic union
      using radiographic views was taken in 2 planes. Clinical outcome evaluated pain,
      motion at the fracture site upon manual stress testing, and recovery of range of
      motion. RESULTS: All nonunions treated operatively healed after a single
      procedure, even though additional PRGF had to be injected in 2 patients. Two of 3
      stable nonunions achieved healing only after repeated percutaneous PRGF
      injections. The mean time from surgery and/or PRGF application to union was 4.9
      months (2-8 months). Complications associated with the described procedure were
      not observed. CONCLUSION: This study, although uncontrolled, shows that PRGF
      technology is clinically safe and can enhance the healing of nonhypertrophic
      nonunions.

PMID- 19104305
TI  - Posttraumatic ankle osteoarthritis after ankle-related fractures.
AB  - OBJECTIVES: The present study analyzes etiologies, pathomechanisms, and
      predisposing factors that lead to the development and progression of
      posttraumatic ankle osteoarthritis (OA) after ankle-related fractures. DESIGN:
      Retrospective cohort study. SETTING: Tertiary health care center. PATIENTS: The
      underlying cohort was 257 painful end-stage ankle OA patients (270 cases)
      presenting to the authors' clinic. Patients from this cohort with a history of
      ankle-related fracture (141 patients) were evaluated. INTERVENTION: Analysis of
      individual clinical and radiologic history since the time of injury; physical and
      radiologic examination at the time of ankle OA. MAIN OUTCOME MEASURES: OA latency
      time, fracture type, treatment methods, complication of fracture healing, soft
      tissue situation, age, pain score, American Orthopedic Foot and Ankle Society
      ankle score, range of motion, radiologic tibiotalar alignment, and radiologic
      ankle OA grading were evaluated. RESULTS: The latency time between injury and end
      stage ankle OA was 20.9 years (1-52 years). Malleolar fracture was the most
      common fracture (53.2%). A negative correlation of the OA latency time with the
      fracture severity was observed for some fracture types (pilon fractures, r = 
      0.4, P < 0.01). Patients with complications during the healing process showed
      significantly shorter OA latency time (P < 0.01). The patients' age at time of
      injury correlated negatively with the OA latency time (r = -0.6, P < 0.01).
      CONCLUSIONS: The present study addresses the link between ankle-related fractures
      and secondary posttraumatic ankle OA. The latency time between injury and OA
      depends on fracture type and severity, occurrence of complications in the healing
      process, and patient-related factors, for example, age.

PMID- 19104306
TI  - Patellar tendon repair with suture anchors using a combined suture technique of a
      Krackow-Bunnell weave.
AB  - Suture repair of the ruptured patellar tendon is the treatment of choice for
      patients requiring operative management. This standard technique includes
      fixation through transosseous tunnels in the patella. The use of suture anchor
      fixation has several advantages over the standard approach, including less
      dissection, decreased surgical time, more accurate suture placement, and a low
      profile construct. Additionally, the pullout strength of suture anchors warrants
      consideration of this technique in these repairs. This article describes using
      suture anchors for repair of the acute ruptured patellar tendon with a
      combination of Krackow and Bunnell sutures.

PMID- 19104307
TI  - Supercutaneous plating: use of a locking compression plate as an external
      fixator.
AB  - Low-profile rigid external fixation can be a helpful adjunct in complex
      posttraumatic cases as part of a staged reconstructive effort. The successful use
      of plates as low-profile external fixators has been described previously by our
      institution. The locking compression plates have been advocated as internal
      external fixators, given their angular stable screw fixation. These properties
      also make them good candidates for external plate fixation; we call this
      technique "supercutaneous plating."

PMID- 19104308
TI  - Irreducible Galeazzi-equivalent fracture in a child: an unusual case.
AB  - We report an unusual case of irreducible Galeazzi-equivalent fracture in a child
      and discuss the factors that prevented reduction in this case.

PMID- 19104309
TI  - Sciatic nerve entrapment in associated both-column acetabular fractures: a report
      of 2 cases and review of the literature.
AB  - Sciatic nerve injury associated with acetabular fractures has been reported in
      most series. Typically, sciatic neuropraxia occurs from traumatic impaction or
      compression due to posterior hip fracture-dislocation. We report 2 patients with
      sciatic nerve entrapment within the posterior column components of their
      associated both-column acetabular fractures. Following neuroplasty through a
      Kocher-Langenbeck surgical approach, both patients' neurologic function improved.
      This unlikely cause of neurologic compromise should be considered in all patients
      with symptoms of sciatic nerve injury or irritation and particularly in the
      presence of a mechanical block during posterior column reduction through an
      ilioinguinal approach.

PMID- 19104310
TI  - Fresh perspectives on intrapartum nursing care.

PMID- 19104311
TI  - Should all laboring women be offered cultures for methicillin-resistant
      Staphylococcus aureus?

PMID- 19104312
TI  - Should all laboring women be offered cultures for methicillin-resistant
      Staphylococcus aureus?

PMID- 19104313
TI  - Oxytocin as a high-alert medication: implications for perinatal patient safety.
AB  - Patient injury from drug therapy is the single most common type of adverse event
      that occurs in the in-patient setting. When medication errors result in patient
      injury, there are significant costs to the patient, healthcare providers, and
      institution. Some medications that have a heightened risk of causing significant
      patient harm when they are used in error are called "high-alert medications."In
      2007, the Institute for Safe Medication Practices added intravenous (IV) oxytocin
      to their list of high-alert medications. This is significant for perinatal care
      providers because oxytocin is a drug that they use quite freguently. Errors that
      involve IV oxytocin administration for labor induction or augmentation are most
      commonly dose related and often involve lack of timely recognition and
      appropriate treatment of excessive uterine activity (tachysystole). Other types
      of oxytocin errors involve mistaken administration of IV fluids with oxytocin for
      IV fluid resuscitation during nonreassuring (abnormal or indeterminate) fetal
      heart rate patterns and/or maternal hypotension and inappropriate elective
      administration of oxytocin to women who are less than 39 completed weeks'
      gestation. Oxytocin medication errors and subsequent patient harm are generally
      preventable. The perinatal team can develop strategies to minimize risk of
      maternal-fetal injuries related to oxytocin administration consistent with safe
      care practices used with other high-alert medications.

PMID- 19104315
TI  - Failure to rescue as a process measure to evaluate fetal safety during labor.
AB  - PURPOSE: To evaluate a perinatal team's clinical responses to the key components
      of the failure to rescue process. METHODS: This retrospective descriptive study
      involved a review of medical records and their accompanying fetal monitoring
      strips for 53 women who had a cesarean birth at term for a nonreassuring fetal
      heart rate pattern. The instrument was the Fetal Safety Failure to Rescue Process
      Tool based on the Agency for Healthcare Research and Quality's Failure to Rescue
      Patient Safety Indicator adapted for perinatal care processes. This tool measured
      four process measures: careful surveillance, timely identification of
      complications, appropriate interventions, and activating a team response. A mean
      total score was computed to determine quality of care based on all four of the
      process measures. RESULTS: The perinatal team's mean total score was 6.6 (SD =
      1.0, range 3-8); the highest possible score was 8. The lowest score was found in
      the team's response with appropriate interventions (lateral positioning,
      intravenous fluid bolus, discontinuation of oxytocin, oxygen administration,
      amnioinfusion, administration of Terbutaline) based on fetal heart rate pattern.
      Interrater reliability of the tool was 90%. CLINICAL IMPLICATIONS: This study
      provided information that may be useful in evaluating processes of care to ensure
      quality care for mothers and babies during labor. The findings formed the basis
      for implementing unit-specific educational programs, including (a) certification,
      continuing education, and documented competence in electronic fetal monitoring
      education to promote consistency in language and understanding of abnormal fetal
      heart rate patterns; (b) review of appropriate documentation of nonreassuring
      fetal heart rate patterns; (c) review and revision, if necessary, of established
      institutional standards and guidelines for appropriate interventions for
      nonreassuring fetal heart rate patterns; (d) changes in standardized forms to
      include times for notification of team members and improved communication, and
      (e) mechanisms for identifying system failures.

PMID- 19104316
TI  - Caring for the extremely obese woman during pregnancy and birth.
AB  - This article describes the special care needed by the pregnant woman who is
      extremely obese. Many pregnant women who are extremely obese have underlying
      medical conditions, and a multidisciplinary, coordinated approach to their care
      involving anesthesia providers, physicians, and the nursing staff is needed to
      develop a detailed plan for vaginal and cesarean births. Such an approach, begun
      preconceptionally or during pregnancy, can enable care to be delivered smoothly
      and safely and should include an evaluation of the unit's equipment and furniture
      to determine if they are appropriate for obese persons. Equipment that should be
      evaluated for size and weight limits include beds, operating room tables,
      commodes, wheelchairs, scales, walkers, blood pressure cuffs, transfer devices,
      and intermittent pneumatic compression devices.

PMID- 19104317
TI  - Clinical disagreements during labor and birth: how does real life compare to best
      practice?
AB  - PURPOSE: To describe how nurses would respond in common clinical situations
      involving disagreement with physician colleagues during labor and birth. STUDY
      DESIGN AND METHODS: An electronic survey, consisting of five clinical
      disagreement case scenarios along with two open-ended questions regarding how to
      promote effective interdisciplinary communication and collaboration, was
      administered via a secure Web site. Seven hundred four obstetric nurses in a mid
      size metropolitan area were invited to participate via mail. One hundred thirty
      three nurses responded. Data were analyzed using descriptive statistics and
      thematic analysis of open-ended text responses. RESULTS: Respondents were
      primarily aged > or =40, experienced in labor nursing, and held a BSN; 35% were
      members of the Association of Women's Health, Obstetric and Neonatal Nurses, 35%
      were certified in electronic fetal monitoring, and 33% were certified in
      inpatient obstetrics. In all five scenarios, most nurses were aware of current
      evidence and published standards of care (range 52%-86%). However, there was a
      wide discrepancy between current evidence/standards and what nurses indicated
      would occur in actual clinical practice. CLINICAL IMPLICATIONS: In this well
      educated and knowledgeable sample of experienced labor nurses, reports of what
      would occur in clinical practice did not match current evidence or standards of
      care. Adequate nursing knowledge may not be an accurate predictor of appropriate
      clinical practice. Confidence in administrative support appears to be one of the
      key factors in empowering nurses to pursue resolution of disagreements in
      patients' best interests, whereas medical hierarchy, fear, and intimidation are
      significant barriers.

PMID- 19104318
TI  - Trends and controversies in labor induction.
AB  - In 2005, the rate of induction of labor for all births in the United States
      calculated from birth certificate data approached 22.3%. In 2006, the Listening
      To Mothers II Study suggested that induction of labor might be as high as 50% if
      attempts at self-induction are considered. All induction methods hold some
      measure of risk for minor and more serious and sometimes even life-threatening
      complications for the mother and fetus. This article contains a review of the
      physiology of labor, accepted pharmacologic and mechanical methods of induction,
      and data about alternative methods women use for induction, including acupuncture
      and herbal preparations. Risks and complications for women undergoing labor
      induction are described, and the role of the nurse in patient education and
      counseling is discussed.

PMID- 19104321
TI  - Women's lived experience of their unexpected birthing process.
AB  - PURPOSE: To describe the essence of women's unexpected birthing experiences.
      METHODS: Descriptive phenomenology using interviews with 10 women who had
      birthing experiences that were not what they had expected, including (1) an
      instrumentally assisted vaginal delivery either by forceps and/or by a vacuum
      extractor, (2) a third- or fourth-degree tear, (3) birth by an emergency cesarean
      birth, or (4) women who perceived that their delivery was incongruent with their
      expectations. Interviews of each woman's birth experience were transcribed using
      Colaizzi's method of analysis. RESULTS: The findings reflected the absence of
      three critical elements-caring, connection, and control-that the women believed
      were missing from their birthing experiences. The lack of caring was demonstrated
      by the statement: "They were there to take care of your baby and not you and
      that's the end of it." The lack of connection was demonstrated by the statement
      "I just didn't have a nurse who was really there." The lack of control was
      demonstrated by this statement: "You're not in control of the experience."
      CLINICAL IMPLICATIONS: Perinatal nurses have an opportunity to influence a caring
      environment in which women feel connected to their nurse and in control of their
      labor and birth. Tailoring nursing care to meet the needs of each mother,
      especially women who are experiencing things they had not expected in labor or
      during birth, may be the key ingredient to ensure optimal birthing experiences.

PMID- 19104320
TI  - Labor and delivery nurses' perceptions of caring for childbearing women in nurse
      managed birthing units.
AB  - PURPOSE: To identify the perceptions of nurses caring for women giving birth in
      nurse-managed, highly technological birthing environments. METHODS: A purposive
      sample of 18 perinatal nurses employed at four different in-hospital birthing
      centers utilizing nurse-managed labor models participated in audio-taped
      interviews. Interviews were transcribed and analyzed for themes. RESULTS: Themes
      included (1) nurses' aversion to birth plans, (2) barriers to the provision of
      supportive care for birthing women, (3) differences in caring for women who are
      medicated versus those who are unmedicated, and (4) the rewards of caring for
      birthing women. Although practicing in very busy, highly technological birthing
      units, many study participants seemed to focus on the value of predictability and
      efficiency guiding the provision of nursing care to birthing women. NURSING
      IMPLICATIONS: Women's birth experiences are heavily influenced by perinatal
      nurses and their care, yet the voices of these nurses have not been represented
      fully in nursing research. Nurses in this study reported multiple challenges in
      the provision of supportive care for their patients, and a wider dialogue on this
      topic within perinatal nursing is warranted. More research is needed on this
      topic, and intervention studies documenting innovative methods of teaching,
      orienting, and continually educating these nurses should be undertaken.

PMID- 19104322
TI  - Breastfeeding immediately after birth.

PMID- 19104323
TI  - Audit trails and electronic record discovery.

PMID- 19104324
TI  - Mamawasi: culturally sensitive birthing for Peruvian women.

PMID- 19104331
TI  - Standardization.

PMID- 19104332
TI  - Barriers in carrying out the dean's role.
AB  - Many new nursing leaders assuming deanships or assistant or interim deanships
      have limited education, experience, or background to prepare them for the job. To
      assist new deans and those aspiring to be deans, the authors of this department,
      2 deans, offer survival tips based on their personal experiences and insights.
      They address common issues, challenges, and opportunities that face academic
      executive teams, such as negotiating an executive contract, obtaining faculty
      lines, building effective work teams, managing difficult employees, and creating
      nimble organizational structure to respond to changing consumer, healthcare
      delivery, and community needs. The authors welcome counterpoint discussions with
      readers.

PMID- 19104333
TI  - Teaching with technology: computer basics.
AB  - In this bimonthly series, the author examines how nurse educators can use
      Internet and Web-based computer technologies such as search, communication, and
      collaborative writing tools, social networking and social bookmarking sites,
      virtual worlds, and Web-based teaching and learning programs. This article
      describes approaches to finding information on the Web. Web-based search tools
      including Internet search engines, organizational databases, and those at the
      library will be discussed. Techniques to evaluate the validity, usefulness, and
      applicability of search outcomes are included.

PMID- 19104334
TI  - Responsible medication disposal safeguards lives and protects the environment.

PMID- 19104335
TI  - Discovering the meaning of reciprocity for students engaged in service-learning.

PMID- 19104337
TI  - Teaching undergraduate nursing research: a collaborative approach.

PMID- 19104339
TI  - Undergraduate students as standardized patients to assess advanced practice
      nursing student competencies.
AB  - Evaluating clinical skills of students in an online distance education program
      can be challenging because of the diverse location of students. The authors
      describe a unique and cost-efficient method of using standardized patients to
      evaluate these skills. The project involved undergraduate students representing
      standardized patients for graduate advanced practice nurse students.

PMID- 19104340
TI  - Assessing new graduate nurse performance.
AB  - New graduate nurses now comprise more than 10% of a typical hospital's nursing
      staff, with this number certain to grow given the increasing numbers of entrants
      into the nurse workforce. Concomitantly, only 10% of hospital and health system
      nurse executives believe their new graduate nurses are fully prepared to provide
      safe and effective care. As part of a multipronged research initiative on
      bridging the preparation-practice gap, the Nursing Executive Center administered
      a national survey to a cross section of frontline nurse leaders on new graduate
      nurse proficiency across 36 nursing competencies deemed essential to safe and
      effective nursing practice. Based on survey data analysis, the authors discuss
      the most pressing and promising opportunities for improving the practice
      readiness of new graduate nurses.

PMID- 19104342
TI  - An untapped resource: using YouTube in nursing education.
AB  - Minimal information is available in the literature addressing video sharing in
      nursing education. Using multiple examples, the authors discuss the use of
      YouTube, a popular video-sharing and social networking site. YouTube is used to
      illustrate theoretical content, involve students, and inspire innovative teaching
      methods. Faculty can use this technology to stimulate student discussions, share
      information, and create a learning community. YouTube stimulates active learning
      and brings new relevance and applications to nursing curriculum.

PMID- 19104344
TI  - Development of a clinical preceptor model.
AB  - To reflect contemporary nursing care, the practicing nurse is in an ideal
      position to shape the clinical experience for student nurses. Although nurse
      preceptors are frequently used to assist in practice education of nursing
      students, their contribution to the creation of these programs has not been
      explored. The author discusses the results of a participatory action research
      study with the aim of creating a preceptor-guided practice education model for
      use throughout an undergraduate bachelor of science in nursing curriculum.

PMID- 19104346
TI  - Integrating caring, scholarship, and community engagement in Mexico.
AB  - To provide students with an unforgettable introduction to community-engaged
      scholarship, students partnered with the local health promoter of a marginalized
      community in northeastern Mexico to plan and conduct diabetes education classes
      with individualized follow-up. The author describes how students and faculty,
      inspired by this vision, integrated service, scholarship, and community
      engagement. The experience strengthened the health promoter's role, empowered
      patients with type 2 diabetes to improve self-care management, and provided
      students the opportunity to measure the impact of their interventions.

PMID- 19104347
TI  - Creative practicum leadership experiences in rural settings.
AB  - Rural healthcare systems provide rich learning environments for nursing students,
      where strong nursing leaders manage care for people with diverse health problems
      across the lifespan. The authors describe the development, implementation, and
      evaluation of rural clinical leadership practicum, a prelicensure course that
      specifically focuses on the application of leadership concepts in small rural
      healthcare systems.

PMID- 19104348
TI  - Community participatory research: student nurses collaborate to reduce lead
      exposure by educating paint retailers.
AB  - Collaboration is a hallmark of the nursing profession as advocated in practice
      standards and nursing experience. The authors describe a unique experience in
      which senior students participated in community-based participatory research,
      working collaboratively with another school, a community organization.

PMID- 19104349
TI  - ANA proposes voluntary code of ethical conduct for the recruitment of foreign
      educated nurses to the United States.

PMID- 19104351
TI  - Is routine cystoscopy an essential intraoperative test at hysterectomy?

PMID- 19104352
TI  - Stage IC ovarian cancer: the clinical significance of intraoperative rupture.

PMID- 19104353
TI  - Urinary tract injury during hysterectomy based on universal cystoscopy.
AB  - OBJECTIVE: To estimate the incidence and location of injury to the urinary tract
      during hysterectomy for benign gynecologic disease. METHODS: This was a
      prospective clinical study in an academic environment performed at three sites.
      Diagnostic cystourethroscopy was performed on all patients after hysterectomy for
      benign disease. RESULTS: Eight hundred thirty-nine patients were enrolled. The
      incidence of urinary tract injury associated with hysterectomy for benign disease
      was 4.3% (39 of 839 cases). The rate of bladder injury was 2.9% (24 of 839
      cases), and rate of ureteral injury was 1.8% (15 of 839 cases). There were three
      cases of simultaneous bladder and ureteral injuries, resulting in a cumulative
      injury rate of 4.3%. The injury detection rate using intraoperative diagnostic
      cystoscopy was 97.4% (817 of 839 cases). The most common site of injury to the
      ureter was at the junction of the ureter and the uterine artery in 80% (12 of 15
      cases) of ureteral injuries. Transection and kinking injuries were the most
      frequent type of injury. There were 21 cases of subnormal dye efflux from the
      ureteral orifices, with no subsequent injury detected on further evaluation.
      CONCLUSION: Ureteral injury occurred most commonly at the level of the uterine
      artery, and transection and kinking injuries were most frequent. Diminished dye
      efflux from ureteral orifices was not associated with injury. LEVEL OF EVIDENCE:
      III.

PMID- 19104354
TI  - Influence of intraoperative capsule rupture on outcomes in stage I epithelial
      ovarian cancer.
AB  - OBJECTIVE: To evaluate the effect of tumor capsule rupture on disease prognosis
      in stage I epithelial ovarian cancer. METHODS: All patients with International
      Federation of Gynecology and Obstetrics stage I epithelial ovarian cancer
      operated on at the Mayo Clinic and The Ohio State University between January 1991
      and December 2007 were identified. Relevant tumor characteristics, procedures
      performed, adjuvant therapies, and follow-up were recorded and analyzed.
      Inclusion criteria included comprehensive staging. Cox proportional hazards,
      Kaplan-Meier estimation, log rank test, and chi test were used for statistical
      analyses. RESULTS: There were 161 cases that met inclusion criteria. Seventy-four
      (46%) patients had intact capsules without positive cytology or surface
      involvement; 61 (38%) had capsule rupture; 33 (20%) had positive cytology; and 22
      (14%) had surface involvement. Overall, 22 of 161 (14%) patients recurred and 12
      of 161 (7%) patients died of their disease. In univariable analysis, both
      intraoperative capsule rupture and positive cytologic washings portended worse
      disease-free survival (hazard ratio [HR] 3.6, 95% confidence interval [CI] 1.5
      8.9; P=.004 and HR 5.2, 95% CI 2.1-12.3; P<.001, respectively) and disease
      specific survival (HR 4.1, 95% CI 1.3-15.4; P=.018 and HR 5.9, 95% CI 1.8-19.3;
      P=.005, respectively). In multivariable analysis, capsule rupture (HR 4.2, 95% CI
      1.8-10.9; P=.001) and positive cytologic washings (HR 6.4, 95% CI 2.5-16.0;
      P<.001) remained independent predictors of worse disease-free survival. Disease
      free survival and disease-specific survival were shortest for stage IC cases with
      positive cytology, surface involvement, or both, that also had intraoperative
      rupture. CONCLUSION: In stage I epithelial ovarian cancer, intraoperative capsule
      rupture portends a higher risk of disease recurrence and death from disease.
      Careful intraoperative removal of ovarian masses is important, and recognizing
      the higher-risk nature of such cases is imperative. LEVEL OF EVIDENCE: III.

PMID- 19104355
TI  - Evidence for frequent regression of cervical intraepithelial neoplasia-grade 2.
AB  - OBJECTIVE: To estimate the fraction of cervical intraepithelial neoplasia 2 (CIN
      2) that might regress if untreated using data from the Atypical Squamous Cells of
      Undetermined Significance/Low-Grade Squamous Intraepithelial Lesions Triage Study
      (ALTS). METHODS: We compared the cumulative occurrence of CIN 2 (n=397) and CIN 3
      or more severe (n=542) diagnosed by the Pathology Quality Control Group in three
      trial arms-immediate colposcopy, human papillomavirus (HPV) triage, and
      conservative management-over the 2-year duration of the ALTS trial. A
      nonparametric test of trend was used to test for differences in the number of CIN
      2 cases relative to number of CIN 3 or more severe cases across study arms with
      an increasing percentage of women referred to colposcopy at baseline. RESULTS:
      There were no significant differences in the cumulative 2-year cumulative CIN 3
      or more severe diagnoses by study arm (10.9%, conservative management; 10.3%,
      HPV; 10.9%, immediate colposcopy) (Ptrend=.8), but there was a significant
      increase in CIN 2 diagnoses (5.8%, conservative management; 7.8%, HPV triage;
      9.9%, immediate colposcopy) (Ptrend<.001) in the study arms, with increasing
      number of women referred to colposcopy at baseline. The relative differences in
      cumulative CIN 2 by study arm among women who tested HPV-16 positive at baseline
      were less pronounced (Ptrend=.1) than women who tested positive for other high
      risk-HPV genotypes (Ptrend=.01). CONCLUSION: There was evidence that
      approximately 40% of undiagnosed CIN 2 will regress over 2 years, but CIN 2
      caused by HPV-16 may be less likely to regress than CIN 2 caused by other high
      risk-HPV genotypes. LEVEL OF EVIDENCE: II.

PMID- 19104356
TI  - The effect of highly active antiretroviral therapy on human papillomavirus
      clearance and cervical cytology.
AB  - OBJECTIVE: To examine the association of highly active antiretroviral therapy
      (HAART) with human papillomavirus (HPV) clearance and progression or regression
      of cervical cytological abnormalities in women with human immunodeficiency virus
      (HIV). METHODS: Five hundred thirty-seven women with HIV participating in the HIV
      Epidemiology Research Study, an observational, multisite cohort study, were
      evaluated semiannually from 1996 to 2000. Cervical Pap tests were collected for
      cervical cytology. Testing for HPV was conducted by polymerase chain reaction.
      Cox proportional hazard models were used to calculate hazard ratios and 95%
      confidence intervals (CIs). Number needed to treat (NNT) at 2 years was
      calculated for HAART. RESULTS: Among women with cervical squamous intraepithelial
      lesions, HAART was associated with an increased likelihood of HPV clearance
      (hazard ratio 4.5, 95% CI 1.2-16.3, NNT 22.4). Use of HAART was not associated
      with an increased likelihood of HPV clearance among women with normal cervical
      cytology (hazard ratio 1.7, 95% CI 0.9-3.1, NNT 6.5) or atypical squamous cells
      of undetermined significance cytology (hazard ratio 1.0, 95% CI 0.4-2.5, NNT
      174.0). Use of HAART was not significantly associated with an increased
      likelihood of cervical cytologic regression (hazard ratio 1.3, 95% CI 1.0-1.7,
      NNT 10.9) or cervical cytologic progression (hazard ratio 0.7, 95% CI 0.6-1.0,
      NNT 12.8). CONCLUSION: Among women with preexisting abnormal cervical cytology,
      HAART was associated with enhanced HPV clearance but not with Pap test
      regression. Close monitoring of women with HIV for cervical cytologic
      abnormalities, regardless of HAART treatment status, is warranted. LEVEL OF
      EVIDENCE: II.

PMID- 19104357
TI  - Cesarean delivery among women with low-risk pregnancies: a comparison of birth
      certificates and hospital discharge data.
AB  - OBJECTIVE: To examine the effect of data source (birth certificate compared with
      hospital discharge records) and the definition of risk on the prevalence of
      cesarean deliveries thought to have "no indicated risk"; eg, the fetus is full
      term, singleton, and in the vertex position, and the mother has no reported
      medical risk factors or complications of labor and/or delivery identified on the
      birth certificate. METHODS: The study is based on data from 565,767 women who
      delivered singleton, vertex neonates with gestational ages of 37-41 weeks in
      Georgia hospitals between 1999 and 2004 and for whom data from birth certificates
      and hospital discharge records could be linked. The percentages of women with
      primary cesarean deliveries who did not have risk indicated on the birth
      certificate and on the hospital discharge record were compared. We also
      calculated the agreement between data sources overall and for each risk
      indicator. RESULTS: Among 40,932 women with primary cesarean deliveries and no
      risk indicated on the birth certificate, 35,761 (87.4%) had a risk identified in
      the hospital discharge data. The overall agreement between data sources on the
      presence of any risk indicator was low (kappa=0.18). Among primary cesarean
      deliveries, the percentage without indicated risk was 58.3% when using birth
      certificate data alone and 3.9% when using hospital discharge data in combination
      with the birth certificate. CONCLUSION: Using birth certificate information alone
      overestimated the proportion of women who had no-indicated-risk cesarean
      deliveries in Georgia. Evidence of many indications for cesarean delivery can be
      found only in the hospital discharge data. The construct of no indicated risk as
      determined from birth certificates should be interpreted with caution, and the
      use of linked data should be considered whenever possible. LEVEL OF EVIDENCE:
      III.

PMID- 19104358
TI  - Elevation of uterine basal tone and fetal heart rate abnormalities after labor
      analgesia: a randomized controlled trial.
AB  - OBJECTIVE: To estimate the effects of combined spinal-epidural and traditional
      epidural analgesia on uterine basal tone and its association with the occurrence
      of fetal heart rate (FHR) abnormalities. METHODS: Seventy-seven laboring patients
      who requested pain relief during labor were randomly assigned to combined spinal
      epidural (n=41) or epidural analgesia (n=36). Uterine contractions and FHR were
      recorded 15 minutes before and after analgesia. Uterine tone was evaluated with
      intrauterine pressure catheter. Primary outcomes were the elevation of baseline
      uterine tone and occurrence of FHR prolonged decelerations or bradycardia after
      analgesia. The influence of other variables such as oxytocin use, hypotension,
      and speed of pain relief were estimated using a logistic regression model.
      RESULTS: The incidence of all outcomes was significantly greater in the combined
      spinal-epidural group compared with epidural: uterine hypertonus (17 compared
      with 6; P=.018), FHR abnormalities (13 compared with 2; P<.01), and both events
      simultaneously (11 compared with 1; P<.01). Logistic regression analysis showed
      the type of analgesia as the only independent predictor of uterine hypertonus
      (odds ratio 3.526, 95% confidence interval 1.21-10.36; P=.022). For the
      occurrence of FHR abnormalities, elevation of uterine tone was the independent
      predictor (odds ratio 18.624, 95% confidence interval 4.46-77.72; P<.001).
      Regression analysis also found a correlation between decrease on pain scores
      immediately after analgesia and the estimated probability of occurrence of
      hypertonus and FHR abnormalities. CONCLUSION: Combined spinal-epidural analgesia
      is associated with a significantly greater incidence of FHR abnormalities related
      to uterine hypertonus compared with epidural analgesia. The faster the pain
      relief after analgesia, the higher the probability of uterine hypertonus and FHR
      changes. CLINICAL TRIAL REGISTRATION: Umin Clinical Trials Registry,
      http://www.umin.ac.jp/ctr/index.htm, UMIN000001186 LEVEL OF EVIDENCE: I.

PMID- 19104359
TI  - Maternal obesity, uterine activity, and the risk of spontaneous preterm birth.
AB  - OBJECTIVE: To assess the associations among maternal obesity, uterine contraction
      frequency, and spontaneous preterm birth in women at risk for spontaneous preterm
      birth. METHODS: In a secondary analysis, we analyzed data from 253 women at risk
      for spontaneous preterm birth (prior spontaneous preterm birth, vaginal bleeding)
      enrolled in a multicenter observational study of home uterine activity monitoring
      at 11 centers. All women wore a uterine activity monitor twice daily from 22
      weeks through 34 weeks of gestation. Mean and maximal contractions/hour at 22-24,
      25-26, 27-28, 29-30, 31-32 weeks, and at or after 33 weeks of gestation were
      compared between overweight/obese women (a body mass index [BMI] at 22-24 weeks
      greater than 25 kg/m) and normal/underweight women (a BMI of 25 kg/m or less) at
      each gestational age interval. Multivariable analysis evaluated the influences of
      BMI, contractions, fetal fibronectin, and transvaginal cervical length on
      spontaneous preterm birth before 35 weeks. RESULTS: Obese/overweight women
      (n=156) were significantly less likely to experience spontaneous preterm birth
      before 35 weeks (8.3% compared with 21.7%, P<.01). For each gestational age
      interval before 32 weeks, obese/overweight women had fewer mean contractions/hour
      (P<.01 for each) and maximal contractions/hour (P<.01 for each) than
      normal/underweight women, although their mean cervical lengths (34.3 mm compared
      with 33.1 mm, P=.25), and fetal fibronectin levels (7.1% compared with 7.2% 50
      ng/mL or more, P=.97) were similar at study enrollment. Obese/overweight status
      was associated with a lower risk of spontaneous preterm birth before 35 weeks
      after controlling for contraction frequency and other factors evaluated at 22-24
      weeks, but not at later periods. CONCLUSION: Obese/overweight women at risk for
      spontaneous preterm birth exhibit less uterine activity and less frequent
      spontaneous preterm birth before 35 weeks of gestation than normal/underweight
      women. LEVEL OF EVIDENCE: II.

PMID- 19104360
TI  - Computerized prenatal genetic testing decision-assisting tool: a randomized
      controlled trial.
AB  - OBJECTIVE: Guidelines for fetal aneuploidy testing recommend that screening and
      diagnostic testing be made available to pregnant women of all ages and that
      providers explain the differences between these tests to help their patients make
      informed testing decisions. We sought to estimate the effect of a computerized,
      interactive prenatal testing decision tool on prenatal testing decision making.
      METHODS: Four hundred ninety-six English- or Spanish-speaking women at 20 or
      fewer weeks of gestation were randomly assigned to view the interactive prenatal
      testing decision tool or the California Department of Health Services'
      educational booklet. Primary outcomes were knowledge, risk awareness,
      intervention satisfaction, decisional conflict, and among women aged at least 35
      years, use of invasive diagnostic testing. RESULTS: Women assigned to the
      interactive prenatal testing decision tool had higher knowledge scores (79.5%
      compared with 64.9%, P<.001), were more likely to correctly estimate their risk
      of procedure-related miscarriage (64.9% compared with 48.1%, P=.002) and carrying
      a Down syndrome-affected fetus (63.5% compared with 15.1%, P<.001), were more
      satisfied with the intervention (P<.001), and had less decision uncertainty
      (P<.001) than controls after viewing the intervention. Most of these differences
      persisted over time. Among women aged at least 35 years, the interactive prenatal
      testing decision tool viewers who were originally less inclined to undergo
      invasive testing were ultimately more likely than similarly inclined controls to
      have amniocentesis or chorionic villus sampling (44.8% compared with 29.2%),
      whereas those who were originally more inclined to undergo an invasive procedure
      ultimately were less likely than similarly inclined controls to have a diagnostic
      procedure (84.6% compared with 94.9%; P=.015 for interaction). CONCLUSION: Using
      an interactive prenatal testing decision tool results in more informed prenatal
      genetic testing decisions than viewing standard educational booklets. CLINICAL
      TRIAL REGISTRATION: Clinicaltrials.gov, www.clinicaltrials.gov, NCT00686062 LEVEL
      OF EVIDENCE: I.

PMID- 19104361
TI  - Breast cancer risk in postmenopausal women using estradiol-progestogen therapy.
AB  - OBJECTIVE: To estimate the risk for breast cancer in Finnish women using
      postmenopausal estradiol (E2)-progestogen therapy. METHODS: All Finnish women
      over 50 years using E2-progestogen therapy for at least 6 months in 1994-2005
      (N=221,551) were identified from the national medical reimbursement register and
      followed up for breast cancer incidence (n=6,211 cases) through the Finnish
      Cancer Registry to the end of 2005. The risk for breast cancer in E2-progestogen
      therapy users was compared with that in the general population. RESULTS: The
      standardized incidence ratio for all types of breast cancer was not elevated
      within the first 3 years of use, but it rose to 1.31 (95% confidence interval
      1.20-1.42) for the use from 3-5 years and to 2.07 (1.84-2.30) with 10 or more
      years of use. Exposure to sequential progestogen for 5 years or more was
      accompanied with a lower risk elevation (1.78, 1.64-1.90) than exposure to
      continuous use (2.44, 2.17-2.72). Oral and transdermal use of E2-progestogen
      therapy was associated with comparable risk elevations for breast cancer. The use
      of norethisterone acetate was accompanied with a higher risk after 5 years of use
      (2.03, 1.88-2.18) than that of medroxyprogesterone acetate (1.64, 1.49-1.79). The
      risk of lobular breast cancer increased sooner than that for ductal cancer and
      was detectable for E2-progestogen therapy use less than 3 years (1.35, 1.18
      1.53). There was no excess risk of breast cancer with distant metastases among E2
      progestogen therapy users. CONCLUSION: The use of E2-progestogen therapy is
      associated with an increased risk for breast cancer after 3 years of use. The
      risk is lower for sequential than for continuous use, but comparable for oral and
      transdermal use. The risk elevation may not be uniform for all progestogens.
      LEVEL OF EVIDENCE: II.

PMID- 19104362
TI  - Postmenopausal estrogen-containing hormone therapy and the risk of breast cancer.
AB  - OBJECTIVE: To investigate the relation of various estrogen-containing hormone
      therapies to the risk of breast cancer, emphasizing the use of the combination of
      estrogen and testosterone. METHODS: Using information from a large U.S.-based
      claims database, we conducted a case-control study in women aged 50 to 64 years
      who had a first-time diagnosis of breast cancer to estimate the effect in users
      of conjugated estrogen alone, conjugated estrogen plus progestin, esterified
      estrogen with methyltestosterone, or esterified estrogen with methyltestosterone
      plus progestin, compared with nonusers. Four controls were matched to each case
      on year of birth and index date. Odds ratios (ORs) were calculated using
      conditional logistic regression. RESULTS: We identified 4,515 cases and 18,058
      matched controls. The OR for users of estrogen alone compared with the nonusers
      was 0.96 (95% confidence interval [CI] 0.88-1.06; 667 cases and 2,900 controls);
      for users of conjugated estrogen plus progestin, it was 1.44 (95% CI 1.31-1.58;
      712 cases and 2,087 controls); and for users of esterified estrogen with
      methyltestosterone and esterified estrogen with methyltestosterone plus
      progestin, the ORs were 1.08 (95% CI 0.86-1.36; 98 cases and 380 controls) and
      1.69 (95% CI 1.03-2.79; 22 cases and 55 controls), respectively. There was an
      increased risk among conjugated estrogen plus progestin users of 48 months or
      more (OR 3.10, 95% CI 2.38- 4.04; 111 cases and 149 controls). CONCLUSION: There
      is no materially increased risk of breast cancer in users of estrogen alone or
      esterified estrogen with methyltestosterone compared with nonusers. There is an
      increased risk among those using conjugated estrogen plus progestin. In
      particular, the risk of breast cancer in women who used conjugated estrogen plus
      progestin for 4 or more years is approximately three times higher than in women
      who are not exposed to hormone therapy, so that the background incidence rate for
      women aged 50 to 64 years, which is around 3 per 1,000, would be increased to
      approximately 9 per 1,000 in women aged 50 to 64 years who have taken conjugated
      estrogen plus progestin for 48 months or more. LEVEL OF EVIDENCE: II.

PMID- 19104363
TI  - Effect of weight change on natural history of pelvic organ prolapse.
AB  - OBJECTIVE: To evaluate the relationship between change in weight and pelvic organ
      prolapse (POP) progression/regression in women during a 5-year period. METHODS:
      Postmenopausal women with uteri (N=16,608), ages 50 to 79, who were enrolled in
      the Women's Health Initiative (WHI) Estrogen plus Progestin Clinical Trial
      between 1993 and 1998 were included in this secondary analysis. Baseline pelvic
      examination, repeated annually, assessed uterine prolapse, cystocele, and
      rectocele using the WHI Prolapse Classification System. Statistical analyses
      included univariate and multiple logistic regression methods. RESULTS: During the
      5-year time period, the majority of women (9,251, 55.7%) gained weight (mean 4.43
      kg, +/-5.95 kg), and the overall rate of prolapse (WHI Prolapse Classification
      System: grades 1-3) increased from 40.9% at baseline to 43.8% at year 5 of
      evaluation. Controlling for age, parity, race, and other health/physical
      variables, being overweight (body mass index [BMI] between 25 and 29.9) or obese
      (BMI of at least 30) at baseline was associated with progression in cystocele,
      rectocele, and uterine prolapse compared with women with healthy BMIs (BMI is
      calculated as weight (kg)/[height (m)]). Specifically, the risk of prolapse
      progression in overweight and obese women as compared with the participants with
      healthy BMIs increased by 32% and 48% for cystocele, by 37% and 58% for
      rectocele, and by 43% and 69% for uterine prolapse, respectively. Adjusting for
      women with prolapse at baseline and baseline BMI, a 10% weight change was
      associated with minimal change in overall POP. Specifically, a 10% weight loss
      was associated with a borderline worsening of uterine prolapse (odds ratio [OR]
      0.93, 95% confidence interval [CI] 0.88-0.97) and a minimal regression of
      cystocele (OR 1.03, 95% CI 1.00-1.05) and rectocele (OR 1.04, 95% CI 1.01-1.07).
      CONCLUSION: Being overweight or obese is associated with progression of POP.
      Weight loss does not appear to be significantly associated with regression of
      POP, suggesting that damage to the pelvic floor related to weight gain might be
      irreversible. LEVEL OF EVIDENCE: II.

PMID- 19104364
TI  - Accuracy of the clinical diagnosis of vaginitis compared with a DNA probe
      laboratory standard.
AB  - OBJECTIVE: To estimate the accuracy of the clinical diagnosis of the three most
      common causes of acute vulvovaginal symptoms (bacterial vaginosis, candidiasis
      vaginitis, and trichomoniasis vaginalis) using a traditional, standardized
      clinical diagnostic protocol compared with a DNA probe laboratory standard.
      METHODS: This prospective clinical comparative study had a sample of 535 active
      duty United States military women presenting with vulvovaginal symptoms. Clinical
      diagnoses were made by research staff using a standardized protocol of history,
      physical examination including pelvic examination, determination of vaginal pH,
      vaginal fluid amines test, and wet-prep microscopy. Vaginal fluid samples were
      obtained for DNA analysis. The research clinicians were blinded to the DNA
      results. RESULTS: The participants described a presenting symptom of abnormal
      discharge (50%), itching/irritation (33%), malodor (10%), burning (4%), or others
      such as vulvar pain and vaginal discomfort. According to laboratory standard,
      there were 225 cases (42%) of bacterial vaginosis, 76 cases (14%) of candidiasis
      vaginitis, 8 cases (1.5%) of trichomoniasis vaginalis, 87 cases of mixed
      infections (16%), and 139 negative cases (26%). For each single infection, the
      clinical diagnosis had a sensitivity and specificity of 80.8% and 70.0% for
      bacterial vaginosis, 83.8% and 84.8% for candidiasis vaginitis, and 84.6% and
      99.6% for trichomoniasis vaginalis when compared with the DNA probe standard.
      CONCLUSION: Compared with a DNA probe standard, clinical diagnosis is 81-85%
      sensitive and 70-99% specific for bacterial vaginosis, Candida vaginitis, and
      trichomoniasis. Even under research conditions that provided clinicians with
      sufficient time and materials to conduct a thorough and standardized clinical
      evaluation, the diagnosis and, therefore, subsequent treatment of these common
      vaginal problems remains difficult. LEVEL OF EVIDENCE: II.

PMID- 19104366
TI  - Attitude and behavior effects in a randomized trial of increased access to
      emergency contraception.
AB  - OBJECTIVE: To explore the effects of providing unrestricted access to emergency
      contraception in advance of need on various psychosocial outcomes and pregnancy.
      METHODS: In the trial, women were randomly assigned to either increased access to
      emergency contraception (two free packs at enrollment with unlimited free
      resupply) or standard access. Participants were evaluated for 1 year for
      pregnancy and other outcomes. Psychosocial data were collected at enrollment and
      at 6 and 12 months. We applied exploratory factor analysis for data reduction. We
      compared the resulting psychosocial factors (including factors related to
      "aversion to pregnancy" and to the perceived "relative benefit" and
      "accessibility" of emergency contraception), two items directly assessing
      substitution, and pregnancy between randomization groups over time. RESULTS: On
      average, women in the increased access group had significantly stronger
      perceptions of both the "relative benefit" and "accessibility" of emergency
      contraception (P<.001 for each). Women in the increased access group were
      significantly more likely to report that they had ever used emergency
      contraception because they did not want to use either condoms or another
      contraceptive method (P<.001). Regarding pregnancy, we noted a significant
      interaction between randomization group and "aversion to pregnancy" (P=.010):
      among the least "averse" women, increased access had a protective effect (hazard
      ratio 0.64, 95% confidence interval 0.39-1.04); among the most "averse" women,
      increased access had a deleterious effect (hazard ratio 1.73, 95% confidence
      interval 1.01-2.98). CONCLUSION: As a result of having unrestricted access, some
      women substituted emergency contraception for their usual contraceptive methods.
      CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov, www.clinicaltrials.gov,
      NCT00060463 LEVEL OF EVIDENCE: I.

PMID- 19104365
TI  - Prediction of treatment outcomes after global endometrial ablation.
AB  - OBJECTIVE: To report rates of amenorrhea and treatment failure after global
      endometrial ablation and to estimate the association between patient factors and
      these outcomes by developing and validating prediction models. METHODS: From
      January 1998 through December 2005, 816 women underwent global endometrial
      ablation with either a thermal balloon ablation or radio frequency ablation
      device; 455 were included in a population-derived cohort (for model development),
      and 361 were included in a referral-derived cohort (for model validation).
      Amenorrhea was defined as cessation of bleeding from immediately after ablation
      through at least 12 months after the procedure. Treatment failure was defined as
      hysterectomy or reablation for patients with bleeding or pain. Logistic and Cox
      proportional hazard regression models were used in model development and
      validation of potential predictors of outcomes. RESULTS: The amenorrhea rate was
      23% (95% confidence interval [CI] 19-28%) and the 5-year cumulative failure rate
      was 16% (95% CI 10-20%). Predictors of amenorrhea were age 45 years or older
      (adjusted odds ratio [aOR] 2.6, 95% CI 1.6-4.3); uterine length less than 9 cm
      (aOR 1.8, 95% CI 1.1-3.1); endometrial thickness less than 4 mm (aOR 2.7, 95% CI
      1.2-6.3); and use of radio-frequency ablation instead of thermal balloon ablation
      (aOR 2.8, 95% CI 1.7-4.9). Predictors of treatment failure included age younger
      than 45 years (adjusted hazard ratio [aHR] 2.6, 95% CI 1.3-5.1); parity of 5 or
      greater (aHR 6.0, 95% CI 2.5-14.8); prior tubal ligation (aHR 2.2, 95% CI 1.2
      4.0); and history of dysmenorrhea (aHR 3.7, 95% CI 1.6-8.5). After global
      endometrial ablation, 23 women (5.1%, 95% CI 3.2-7.5%) had pelvic pain, three
      (0.7%, 95% CI 0.1-1.9%) were pregnant, and none (95% CI 0-0.8%) had endometrial
      cancer. CONCLUSION: Population-derived rates and predictors of treatment outcomes
      after global endometrial ablation may help physicians offer optimal preprocedural
      patient counseling. LEVEL OF EVIDENCE: II.

PMID- 19104367
TI  - Trocar-guided transvaginal mesh repair of pelvic organ prolapse.
AB  - OBJECTIVE: To prospectively assess clinical outcomes after pelvic organ prolapse
      repair with a standardized trocar-guided surgical device using polypropylene
      mesh. METHODS: This was a prospective multicenter cohort study performed
      throughout 26 clinics. Evaluation at baseline, 2 months, and 1 year after surgery
      included prolapse grading using the pelvic organ prolapse quantification system
      (POP-Q) and symptom assessment using the Incontinence Impact Questionnaire (IIQ
      7) and Urogenital Distress Inventory (UDI-6). For the purpose of this study,
      postoperative POP-Q stage 0-I was considered anatomic cure. RESULTS: Two-hundred
      sixty-one patients were included in the study; 232 (89%) attended the 1-year
      follow-up. Mean+/-standard deviation age at surgery was 66.3+/-9.4 years.
      Anatomic cure 1 year after surgery was observed in 96 of 121 women (79%) after
      anterior repair with mesh (P<.001), and 56 of 68 (82%) after posterior repair
      with mesh (P<.001). For combined anterior and posterior mesh repair, cure was 51
      of 63 (81%) and 54 of 63 (86%) for the anterior and posterior compartment,
      respectively (P<.001 for both). Bladder and rectal perforations occurred in 9 of
      252 patients (3.4%). Vaginal erosions, the majority mild to moderate, occurred in
      26 of 232 cases (11%). Surgical intervention due to mesh exposure occurred in
      seven cases (2.8%). There were significant quality-of-life improvements in all
      domains of the IIQ-7. Despite significant improvements in UDI-6 scores, symptoms
      specific for stress urinary incontinence were not ameliorated. CONCLUSION: Trocar
      guided transvaginal mesh surgery for pelvic organ prolapse is associated with
      satisfactory objective and subjective outcomes 1 year after surgery. CLINICAL
      TRIAL REGISTRATION: ClinicalTrials.gov, www.clinicaltrials.gov, NCT00402844 LEVEL
      OF EVIDENCE: II.

PMID- 19104368
TI  - Sexual dysfunction after trocar-guided transvaginal mesh repair of pelvic organ
      prolapse.
AB  - OBJECTIVE: To estimate sexual dysfunction before and after trocar-guided
      transvaginal mesh surgery for pelvic organ prolapse. METHODS: Sexually active
      women participating in a prospective multicenter study were recruited at 26
      centers. All participants underwent a standardized surgical procedure and were
      evaluated before (n=105) and 1 year after (n=84) surgery using the short form of
      the Pelvic Organ Prolapse/Urinary Incontinence Sexual Questionnaire (PISQ-12).
      Nonparametric statistics were used for comparisons. RESULTS: Mean age at surgery
      was 61.5 years (standard deviation [SD] 7.6), median parity was 2 (range, 1-6),
      and mean body mass index was 26.8 (SD 4.3) (body mass index is calculated as
      weight (kg)/[height m]). Anterior transvaginal mesh repair was performed in 46
      patients (44%), posterior in 26 patients (25%), and combined anterior and
      posterior in 33 patients (31%). Overall sexual function scores worsened from 15.5
      (SD 8.0) at baseline to 11.7 (SD 6.9) 1 year after surgery (P<.001). The trend
      toward deteriorating sexual function scores was similar for all three surgical
      procedures. There was an overall worsening of all symptoms in the behavioral
      emotive and partner-related items, whereas improvements were observed in physical
      function. Overall rates and severity of dyspareunia in specific neither improved
      nor worsened. CONCLUSION: Sexual function scores deteriorate 1 year after trocar
      guided transvaginal mesh surgery. The worsening was attributed primarily to a
      worsening in behavioral-emotive and partner-related items. Anatomical cure after
      surgery was not associated with improved PISQ scores. CLINICAL TRIAL
      REGISTRATION: ClinicalTrials.gov, www.clinicaltrials.gov, NCT00402844 LEVEL OF
      EVIDENCE: II.

PMID- 19104369
TI  - Effect of mode of delivery on the incidence of urinary incontinence in
      primiparous women.
AB  - OBJECTIVE: To estimate the effect of mode of delivery on the incidence of urinary
      incontinence in primiparous women. METHODS: A population-based survey was mailed
      to all Oregon women who delivered a liveborn neonate in a 1-year period. Data
      were collected on urinary incontinence, childbirth experience, and other risk
      factors for incontinence at 3-6 months postpartum. Univariable analyses were
      conducted using t tests and Wilcoxon rank-sum tests for continuous variables and
      chi tests for categorical variables. Logistic regression analyses were used to
      estimate odds ratios and 95% confidence intervals for demographic and clinical
      risk factors. RESULTS: A total of 15,787 women completed the survey, for a
      response rate of 39%. Of these women, 5,599 were primiparous, completed the
      survey in the desired timeframe, submitted information on their urinary
      continence, and did not have incontinence before pregnancy. A total of 955
      (17.1%) reported leakage of urine. Women who had vaginal deliveries were more
      likely to have urinary incontinence than women who had cesarean deliveries (odds
      ratio 4.96 [95% confidence interval 3.82-6.44], P<.001). This risk increased with
      assisted delivery and perineal laceration. No statistical difference in the
      incidence of urinary incontinence was found among women who had elective cesarean
      deliveries (6.1%), women who had cesarean deliveries after laboring (5.7%), and
      women who had cesarean deliveries after laboring and pushing (6.4%). CONCLUSION:
      Urinary incontinence is common in the immediate postpartum period after a woman's
      first pregnancy. Although vaginal delivery increases the risk of urinary
      incontinence, labor and pushing alone without vaginal delivery do not appear to
      increase this risk significantly. LEVEL OF EVIDENCE: II.

PMID- 19104370
TI  - Adverse effects of antenatal glucocorticoids on cerebral myelination in sheep.
AB  - OBJECTIVE: To determine in fetal sheep the effect of betamethasone on myelination
      in relation to stage of myelination, number of treatment courses, dose, and route
      of administration. METHODS: Fetal expression of myelin basic protein (MBP), a
      marker of mature oligodendrocytes and myelin, was determined between 0.27 and
      0.93 gestation. Short-term betamethasone effects were examined 24 hours after one
      maternal intramuscular treatment course (weight adjusted to equal the clinical
      dose of 2 x 8 mg betamethasone to a 70-kg woman) at 0.63, 0.75, and 0.87
      gestation or after continuous 48-hour fetal intravenous infusion at 0.75 and 0.87
      gestation. Lasting effects were examined 20 days after one and two treatment
      courses weight-adapted to the clinical dose of 2 x 8 mg or 2 x 12 mg
      betamethasone at 0.75 gestation. RESULTS: Myelin basic protein immunoreactivity
      was first detected in the internal capsule at 0.53 gestation, followed by the
      centrum semiovale, the superficial white matter, and corpus callosum at 0.63
      gestation. Within 24 hours after treatment, betamethasone reduced the number of
      mature oligodendrocytes and MBP immunoreactivity. The effect decreased with
      gestational age. Maternal and fetal betamethasone administration had similar
      effects. Loss of MBP immunoreactivity was not reversed 20 days after two
      treatment courses, independent of dose. CONCLUSION: Betamethasone-induced delayed
      cerebral myelination is dependent on the stage of brain development in sheep.
      Betamethasone-related disturbances in myelination and any potential contribution
      to childhood behavior deficits need to be confirmed in clinical studies.

PMID- 19104371
TI  - Pharma "phree".

PMID- 19104372
TI  - Female cosmetic genital surgery.
AB  - Genital plastic surgery for women has come under scrutiny and has been the topic
      of discussion in the news media, online, and in medical editorials. In the
      absence of measurable standards of care, lack of evidence-based outcome norms,
      and little standardization either in nomenclature or training requirements,
      concern has been raised by both ethicists and specialty organizations.Some women
      request alteration of their vulvas and vaginas for reasons of cosmesis,
      increasing self-esteem, and improving sexual function. Patients must be assured
      their surgeon is properly trained and should understand that few validated long
      term safety or outcome data are presently available in this relatively new field.
      Women also should be made aware that, although they may wish to cosmetically or
      physically alter their external genitalia, this does not mean that they are
      developmentally or structurally "abnormal." It is important that training
      guidelines for practitioners be established and that long-term outcome,
      psychosexual, and safety data be published. The genital plastic surgeon must have
      sufficient training in sexual medicine to withhold these procedures from women
      with sexual dysfunction, mental impairment, or body dysmorphic disorder. In an
      atmosphere in which trademarked marketing terms are becoming part of the lexicon,
      a more descriptive terminology is suggested, incorporating the terms
      "labiaplasty," "reduction of clitoral hood," "perineoplasty," "hymenoplasty," and
      "vaginoplasty." The term "female cosmetic genital surgery" is presented as a
      descriptive umbrella encompassing these genital plastic procedures.

PMID- 19104373
TI  - A medical journal editor's role in exposing an unethical research study.
AB  - The involvement of Dr. Richard Mattingly, Editor of Obstetrics & Gynecology
      between 1972 and 1985, in the publication of an article on carcinoma in situ
      (CIS) of the cervix, facilitated exposure of an unethical study into the natural
      history of CIS of the cervix (now termed cervical intraepithelial neoplasia 3) by
      Dr. Herbert Green. The object of Dr. Green's study was to verify his premise that
      CIS was not a precursor of invasive cancer, and he published his "atypical
      viewpoint" that CIS was a benign disorder in international medical journals and
      the lay press. Alarmed by the number of women developing cancer and frustrated by
      the failure of the hospital authorities to deal with the problem, Dr. Bill
      McIndoe began presenting his interpretation of Dr. Green's study at international
      scientific meetings. Dr. Mattingly was aware of both Dr. Green's previous
      publications and the difficulties facing Dr. McIndoe, and he encouraged Dr.
      McIndoe to publish his data in Obstetrics & Gynecology. The correspondence
      between Dr. Mattingly, a senior U.S. academic and journal editor wishing to
      publish important scientific data, and Dr. McIndoe, an unknown antipodean
      clinician intent on revealing an unethical experiment, provides important lessons
      for all who practice medicine, in particular those in positions of
      responsibility.

PMID- 19104374
TI  - Medications in pregnancy and lactation: part 1. Teratology.
AB  - One of the least-developed areas of clinical pharmacology and drug research is
      the use of medication during pregnancy and lactation. This article is the first
      in a two-part series designed to familiarize physicians with many aspects of the
      drugs they commonly prescribe for pregnant and breast-feeding women. Almost every
      pregnant woman is exposed to some type of medication during pregnancy. Although
      the majority of pregnant and breast-feeding women consume clinically indicated or
      over-the-counter drug preparation regularly, only few medications have
      specifically been tested for safety and efficacy during pregnancy. There is scant
      information on the effect of common pregnancy complications on drug clearance and
      efficacy. Often, the safety of a drug for mothers, their fetuses, and nursing
      infants cannot be determined until it has been widely used. Absent this crucial
      information, many women are either refused medically important agents or
      experience potentially harmful delays in receiving drug treatment. Conversely,
      many drugs deemed "safe" are prescribed despite evidence of possible
      teratogenicity. Novel research and diagnostic applications evolving from the
      opportunities presented by the advances in genomics and proteomics are now
      beginning to affect clinical diagnosis, vaccine development, drug discovery, and
      unique therapies in a modern diagnostic-therapeutic framework-part of the new
      scientific field of theranostics. This review critically explores a number of
      recently raised issues in regard to the use of several classes of medications
      during gestation and seeks to provide a general and concise resource on drugs
      commonly used during pregnancy and lactation. It also seeks to make clinicians
      more aware of the controversies surrounding some drugs in an effort to encourage
      safer prescribing practices through consultation with a maternal-fetal medicine
      specialist and through references and Web sites that list up-to-date information.

PMID- 19104375
TI  - Benefits and risks of oral diabetes agents compared with insulin in women with
      gestational diabetes: a systematic review.
AB  - OBJECTIVE: Little is known about the comparative risks and benefits of medical
      treatments for gestational diabetes mellitus (GDM). We conducted a systematic
      review of randomized controlled trials and observational studies of maternal and
      neonatal outcomes in women with GDM treated with oral diabetes agents compared
      with all types of insulin. DATA SOURCES: We searched four electronic databases
      from inception through January 2007. Terms for GDM, insulins, and oral
      hypoglycemic agents were used in the search. Two investigators independently
      reviewed titles and abstracts, performed data abstraction on full articles, and
      assessed study quality. METHOD OF STUDY SELECTION: Articles were excluded if they
      had no comparison group or did not use a standard diagnosis of GDM (3-hour, 100-g
      oral glucose tolerance test or 2-hour, 75-g oral glucose tolerance test). Nine
      studies met our inclusion criteria, four randomized controlled trials (n=1,229
      participants) and five observational studies (n=831 participants). Data were
      abstracted on study characteristics, gestational age at treatment, medication
      dosage, and length of follow-up. Outcomes included glycemic control, infant birth
      weight, neonatal hypoglycemia, and congenital anomalies. TABULATION, INTEGRATION,
      AND RESULTS: Two trials compared insulin to glyburide; one trial compared
      insulin, glyburide, and acarbose; and one trial compared insulin to metformin. No
      significant differences were found in maternal glycemic control or cesarean
      delivery rates between the insulin and glyburide groups. A meta-analysis showed
      similar infant birth weights between women treated with glyburide and women
      treated with insulin (mean difference -93 g) (95% confidence interval -191 to 5
      g). There was a higher proportion of infants with neonatal hypoglycemia in the
      insulin group (8.1%) compared with the metformin group (3.3%) (P=.008). The rate
      of congenital malformations did not differ between pregnancies treated with
      insulin and those treated with oral agents. Observational studies were limited by
      selection bias and confounding. CONCLUSION: No substantial maternal or neonatal
      outcome differences were found with the use of glyburide or metformin compared
      with use of insulin in women with GDM.

PMID- 19104376
TI  - Active compared with expectant delivery management in women with gestational
      diabetes: a systematic review.
AB  - OBJECTIVE: We conducted a systematic review to estimate benefits and harms of the
      choice of timing of induction or elective cesarean delivery based on estimated
      fetal weight or gestational age in women with gestational diabetes mellitus
      (GDM). DATA SOURCES: An electronic literature search was performed using MEDLINE,
      EMBASE, the Cumulative Index to Nursing and Allied Health Literature, and The
      Cochrane Central Register of Controlled Trials from inception to January 2007.
      METHODS OF STUDY SELECTION: Two investigators independently reviewed titles and
      abstracts, assessed article quality, and abstracted data. Maternal outcomes
      included cesarean delivery and operative vaginal delivery. Neonatal outcomes
      included birth weight, macrosomia, large for gestational age, shoulder dystocia,
      birth trauma, neonatal intensive care admissions, and perinatal mortality.
      TABULATION, INTEGRATION, AND RESULTS: Five studies met our inclusion criteria:
      one randomized controlled trial (RCT) and four observational studies. The RCT
      (n=200) compared the effect of labor induction at term with expectant management.
      The proportion of newborns with birth weight greater than the 90th percentile was
      significantly greater in the expectant-management group (23% compared with 10%
      with active induction, P=.02); there were no significant differences in rates of
      cesarean delivery, shoulder dystocia, neonatal hypoglycemia, or perinatal deaths.
      The four observational studies suggest a potential reduction in macrosomia and
      shoulder dystocia with labor induction and cesarean delivery for estimated fetal
      weight indications, but there was insufficient evidence to assess other clinical
      outcomes. CONCLUSION: Active rather than expectant management of labor at term
      for women with GDM may reduce rates of macrosomia and related complications.
      Further RCTs and observational studies with a broader range of outcomes are
      needed for sufficient evidence to inform clinical practice.

PMID- 19104377
TI  - Package of care for active management in labour for reducing caesarean section
      rates in low-risk women.
AB  - BACKGROUND: Approximately 15% of women have caesarean sections (CS) and while the
      rate varies, the number is increasing in many countries. This is of concern
      because higher CS rates do not confer additional health gain but may adversely
      affect maternal health and have implications for future pregnancies. Active
      management of labour has been proposed as a means of reducing CS rates. This
      refers to a package of care including strict diagnosis of labour, routine
      amniotomy, oxytocin for slow progress and one to one support in labour.
      OBJECTIVES: To determine whether active management of labour reduces CS rates in
      low-risk women and improves satisfaction. SEARCH STRATEGY: We searched the
      Cochrane Pregnancy and Childbirth Group's Trials Register (February 2008),
      MEDLINE (1966 to December 2007), EMBASE (1980 to 2007), MIDIRS (1985 to 2007) and
      CINAHL (1982 to 2007). SELECTION CRITERIA: Randomised controlled trials comparing
      low-risk women receiving a predefined package of care (active management) with
      women receiving routine (variable) care. Trials where slow progress had been
      diagnosed before entry into the trial were excluded. DATA COLLECTION AND
      ANALYSIS: At least two review authors extracted data. We assessed included
      studies for risk of bias. MAIN RESULTS: We included seven trials, with a total of
      5390 women. The quality of studies was mixed. The CS rate was slightly lower in
      the active management group compared to the group that received routine care, but
      this difference did not reach statistical significance (RR 0.88, 95% CI 0.77 to
      1.01). However, in one study there was a large number of post-randomisation
      exclusions. On excluding this study, CS rates in the active management group were
      statistically significantly lower than in the routine care group (RR 0.77 95% CI
      0.63 to 0.94). More women in the active management group had labours lasting less
      than twelve hours, but there was wide variation in length of labour within and
      between trials. There were no differences between groups in use of analgesia,
      rates of assisted vaginal deliveries or maternal or neonatal complications. Only
      one trial examined maternal satisfaction; the majority of women (over 75%) in
      both groups were very satisfied with care. AUTHORS' CONCLUSIONS: Active
      management is associated with small reductions in the CS rate, but it is highly
      prescriptive and interventional. It is possible that some components of the
      active management package are more effective than others. Further work is
      required to determine the acceptability of active management to women in labour.

PMID- 19104383
TI  - Home uterine activity monitoring: the role of medical evidence.

PMID- 19104386
TI  - Mode of delivery: toward responsible inclusion of patient preferences.

PMID- 19104388
TI  - The 2008 National Institute of Child Health and Human Development workshop report
      on electronic fetal monitoring: update on definitions, interpretation, and
      research guidelines.

PMID- 19104390
TI  - Postpartum sterilization: small incision, big complication.

PMID- 19104391
TI  - ACOG Committee Opinion No. 423: motivational interviewing: a tool for behavioral
      change.

PMID- 19104392
TI  - ACOG Committee Opinion No. 424: abortion access and training.

PMID- 19104393
TI  - ACOG Committee Opinion No. 425: health care for undocumented immigrants.

PMID- 19104394
TI  - Transplantation: a report of progress.

PMID- 19104395
TI  - Introduction of the President of The transplantation society, Nicholas Tilney.

PMID- 19104396
TI  - The Transplantation Society: a global presence.

PMID- 19104397
TI  - Medawar Prize presentation-citation for Jean-Michel Dubernard.

PMID- 19104398
TI  - Medawar prize acceptance speech "connections".

PMID- 19104399
TI  - Modernization of the organ transplantation program in China.

PMID- 19104400
TI  - The Transplantation Society recognition awards 2008.

PMID- 19104402
TI  - A novel immunosuppressive strategy combined with preemptive antiviral therapy
      improves the eighteen-month mortality in HCV recipients transplanted with aged
      livers.
AB  - BACKGROUND: Donor's age and immunosuppression influence the severity of hepatitis
      C virus (HCV) recurrence. We analyzed the 18-month mortality in 302 consecutive
      HCV recipients, divided into three groups, with homogeneous immunosuppression and
      preemptive antiviral therapy in the last group. PATIENTS: Group 1: one hundred
      thirty-three patients (1996-2000) mainly received a triple therapy (steroids-
      cyclosporine A [CyA]-azathioprine); first line treatment of biopsy-proven acute
      rejection (BPAR) was with steroid boluses; second-line with OKT3. Group 2: ninety
      one patients (2001-2003) mainly received a double therapy (steroids-CyA) and
      induction with anti-CD25 antibody; first-line BPAR treatment was increased
      dose/switch of the calcineurin inhibitor; second-line steroid boluses; third-line
      extracorporeal photopheresis (ECP). Group 3: seventy-eight patients (2004-June
      2006) mainly received a monotherapy (CyA) associated with ECP and induction with
      anti-CD25 antibody; first-line BPAR treatment was increased dose/switch of
      calcineurin inhibitor with increased ECP frequency, second-line steroid boluses,
      and third-line retransplantation. RESULTS: Median donor's age increased from 54
      (13-84) years in group 1 to 60 (10-93) years in group 2 and 66 (17-84) years in
      group 3 (P<0.001). Overall mortality in groups 1, 2, and 3 decreased from 28.6%
      to 22% and 10.2% respectively (P = 0.003); HCV-related mortality from 7.5% and
      12.1% to 1.3%, respectively (P = 0.029). BPAR were 33.8% in group 1 and 9.0% in
      group 3. Applicability of the preemptive antiviral therapy in group 3 was 69.2%.
      Sustained viral clearance occurred in 38.9% of 36 patients who completed the
      protocol. At multivariate analysis, a single-drug immunosuppressive regimen was
      the only variable independently associated with survival (P=0.05). CONCLUSION:
      Low and steady immunosuppression combined with preemptive antiviral therapy
      significantly improved the short-term mortality of HCV recipients transplanted
      with aged organs. Prolonged follow-up will assess whether this benefit is
      maintained in the long run.

PMID- 19104401
TI  - Long-term insulin independence and improvement in insulin secretion after
      supplemental islet infusion under exenatide and etanercept.
AB  - BACKGROUND: Progressive graft dysfunction (GDF) and loss of insulin independence
      (II) have been invariably observed in islet transplant recipients under the
      "Edmonton protocol." To reestablish II, we performed supplemental islet infusions
      (SI) in recipients of allogeneic islet transplant alone, displaying GDF. To
      improve the engraftment and long-term graft function of SI, exenatide (EXN) and
      etanercept treatment at islet infusion, and long-term EXN treatment were tested
      in a non-randomized pilot clinical trial. METHODS: Patients with GDF received SI
      under Edmonton-like immunosuppression with daclizumab induction, either without
      interventions (SI-control; n=5) or with EXN and etanercept treatment (SI-EXN;
      n=4). Clinical and metabolic profiles were assessed during 18-month follow-up.
      RESULTS: Long-term II (18 months) was observed in 100% of SI-EXN and in 20% of SI
      control (P=0.04). SI-EXN subjects demonstrated restoration of function better
      than that seen after initial islet infusions. Comparison of SI-EXN and SI-control
      groups demonstrated better responses in SI-EXN subjects at 3 months post-SI.
      During the 18 months of follow-up, function was sustained in the SI-EXN subjects
      better than in SI-controls. Acute effects of EXN during mixed meal tolerance test
      and intravenous glucose tolerance test results in improved first and second phase
      insulin release in response to intravenous glucose tolerance test and suppressed
      postprandial hyperglucagonemia after mixed meal tolerance test. CONCLUSION: These
      results suggest that the combination of EXN and etanercept improve engraftment
      and long-term islet survival and function in subjects undergoing SI. This data,
      however, must be interpreted with some caution because of small sample size, lack
      of randomization, and sequential comparison with historical controls.

PMID- 19104403
TI  - Early experience of paired living kidney donation in the United kingdom.
AB  - BACKGROUND: Paired living kidney donation became possible in the United Kingdom
      in 2006 after the introduction of a new legal framework for organ donation. A
      national matching scheme was subsequently established and we report the early
      United Kingdom experience of paired donation. METHODS: A new national matching
      algorithm was developed for the introduction of paired donation in the United
      Kingdom. Initially, all potential two-way exchanges were identified with
      prioritization according to a points system based on geographical proximity
      between pairs, calculated human leukocyte antigen antibody reaction frequency
      (cRF), HLA mismatch of potential transplant, and donor-donor age difference.
      Three-way exchanges were additionally considered after the first year. RESULTS:
      The list for paired donation has grown steadily as 3-monthly "matching runs" have
      been carried out from April 2007, and in July 2008 there were 85 couples
      registered. Eight paired donor transplants have resulted with a number of
      identified exchanges unable to proceed. Fewer potential exchanges have been
      identified than expected due to blood group composition (47 of 85 donors of group
      A compared with 16 potential recipients [A, AB]) and high levels of cRF (95%-100%
      in 35% of patients) among listed patients. CONCLUSIONS: Paired donation has been
      introduced successfully in the United Kingdom, adding to living donor transplant
      activity. The new national program has yielded fewer transplants than initially
      anticipated but as the scheme evolves, with the use of altruistic, nondirected
      donors to start a "chain" of transplants, an increase in the number of successful
      paired donation transplants is anticipated.

PMID- 19104404
TI  - Analysis of the wait list and deaths among candidates waiting for a kidney
      transplant.
AB  - BACKGROUND: The status (active vs. inactive) and the characteristics of patients
      waiting for a kidney transplant and those dying on the kidney waiting list were
      analyzed to make a current assessment of the kidney waitlist. Candidates
      designated as inactive on the kidney waiting list were examined to determine
      total length of time with inactive status and total time on the list. METHODS:
      The number and proportion of kidney waitlist candidates with inactive status at
      any point in time on the waiting list has increased substantially over the last
      several years. At the end of 2007, 24,624 candidates on the kidney waiting list
      (32.8%) were categorized as inactive compared with 9186 (16.1%) at the end of
      2003. RESULTS: The percentage of patients who died categorized as inactive on the
      kidney waiting list has also increased markedly from 31% (n=1197) in 2003 to 52%
      (2431) in 2007. Among the 2431 candidates, who died with inactive status while
      waiting for a kidney during 2007, 1281 (53%) were inactive for longer than 1 year
      over the entire course of their time on the waiting list, and 1132 (47%) were not
      listed as active status consecutively for more than 1 year before their death.
      CONCLUSION: "Inactive" patients are not eligible to receive an offer for a
      deceased donor kidney, even though they are on the list. Patients who died
      inactive and never received an offer for a kidney during the period of listing
      are not served well by extended periods of inactivity.

PMID- 19104405
TI  - Time-zero renal biopsy in living kidney transplantation: a valuable opportunity
      to correlate predonation clinical data with histological abnormalities.
AB  - BACKGROUND: Living kidney donation is increasing as a partial solution for wait
      listed patients. Despite properly followed guideline criteria for donor
      selection, current reports identify unsuspected renal pathology at
      preimplantation or time-zero biopsy (T0-RBx). METHODS: T0-RBx was evaluated for
      following: interstitial fibrosis (IF), tubular atrophy (TA), arteriolar
      hyalinosis (AH), mesangial increase (MI), and glomerulosclerosis (GS).
      Predonation data were demography, body weight, body mass index (BMI),
      systolic/diastolic blood pressure (BP), serum creatinine (SCr), estimated
      glomerular filtration rate (eGFR), and proteinuria. RESULTS: Two hundred nineteen
      T0-RBx were analyzed. Of these 54.4% had abnormal findings, namely, IF in 29%, TA
      in 13%, MI in 12%, AH in 10%, and GS in 10%. Mean clinical data were as follows:
      age 35.4+/-10 years, weight 66.27+/-10.14 kg, BMI 25.53+/-2.99, systolic BP 115+/
      9 mm Hg, diastolic BP 74+/-7 mm Hg, SCr 0.91+/-0.25 mg/dL, eGFR 96+/-16.65
      mL/min, and proteinuria 70.25+/-62.8 mg/24 hr. A total of 56.7% were women. IF
      correlated to age (r=0.22, P=0.001) and SCr (r=0.19, P=0.005); TA to diastolic BP
      (r=0.15, P=0.03) and proteinuria (r=0.20, P=0.009); AH to SCr (r=0.15, P=0.02)
      and eGFR (r=-0.16, P=0.018); MI to BMI (r=0.13, P=0.047). Multivariate analysis
      failed to sustain the significant associations found on bivariate analysis, most
      likely due to a low event/parameter relation and sample size. CONCLUSIONS: A
      significant correlation was established between T0-RBx findings and clinical
      predonation parameters. Whether these mild histologic findings at the time of
      kidney donation represent a higher risk for the remaining kidney ought to be
      evaluated during follow-up. In an era, when living kidney donation is increasing,
      we advise closer donor surveillance to modify risk factors that participate in
      kidney damage progression.

PMID- 19104406
TI  - Patient outcomes in two steroid-free regimens using tacrolimus monotherapy after
      daclizumab induction and tacrolimus with mycophenolate mofetil in liver
      transplantation.
AB  - INTRODUCTION: Long-term steroid administration may predispose liver transplant
      recipients to infectious and metabolic complications. Maintaining effective
      immunoprophylaxis while minimizing the negative consequences of steroid therapy
      could be a key factor in improving clinical outcomes. METHODS: Six hundred two
      patients were randomized to receive tacrolimus (TAC) immunosuppression with a
      single-steroid bolus and two doses of daclizumab (DAC) or mycophenolate mofetil
      (MMF). RESULTS: The incidence of biopsy-proven acute rejection was 19.7% in the
      TAC/DAC group and 16.2% in the TAC/MMF group (ns). Three-month patient and graft
      survival were similar. Steroid use at month-3 was low at 5.5% in the TAC/DAC
      group and 3.9% in the TAC/MMF group. Significantly higher incidences of causally
      related adverse events (AEs) and significantly more dose modifications,
      interruptions, or discontinuations due to an AE were reported with TAC/MMF. Study
      withdrawal due to leucopenia was significantly higher with TAC/MMF (0.0% vs.
      1.7%. P<or=0.05). AEs were generally reported less frequently in the TAC/DAC
      group. However, specifically headache and supraventricular arrhythmia were
      significantly higher with TAC/DAC, whereas leucopenia and bacterial infection
      were significantly higher with TAC/MMF. Laboratory indices of renal function were
      similar, and increases in serum lipids were negligible in both groups. Incidences
      of de novo diabetes mellitus (>or=2 fasting plasma glucose values >or=7.0 mmol/L)
      were low at 9.5% (TAC/DAC) and 11.0% (TAC/MMF). CONCLUSION: Both TAC-based
      regimens allowed optimization of immunoprophylaxis while eliminating some of the
      negative consequences associated with steroids. Efficacy outcomes were
      comparable; however, TAC monotherapy after DAC induction was associated with
      significantly less leucopenia and less bacterial infection than a dual regimen
      incorporating MMF.

PMID- 19104408
TI  - Definitions of warm ischemic time when using controlled donation after cardiac
      death lung donors.
AB  - BACKGROUND: The clinical limits and most relevant definition of warm ischemic
      time (WIT) for donation after cardiac death (DCD) donor lungs are unclear.
      METHODS: Prospectively collected postwithdrawal and postmortem DCD donor
      hemodynamics and oximetry were temporally studied to determine the range,
      pattern, and potential clinical relevance to DCD clinical lung transplant
      outcomes. Different definitions of WIT were examined including the timing of
      withdrawal, systolic blood pressure less than 50 mm Hg, initiation of ventilation
      or the onset of pulmonary arterial flush. Intensive care unit donor management
      was strictly according to local practice guidelines. RESULTS: Between May 2006
      and August 2008, 24 DCD donor referrals led to 13 attempted lung retrievals,
      resulting in nine bilateral lung transplantions (three donors did not arrest
      within prescribed 90 min window and one donor had unacceptable lungs). The mean
      WIT for the 10 retrieved DCD lungs varied according to the different potential
      definitions and ranged from 10 to 42 min (absolute range, 3-65 min). Donor blood
      pressure, heart rate, and oximetry fell linearly from the time of withdrawal,
      leading to cardiac arrest on average 13.8 min later. CONCLUSIONS: From a
      practical perspective, a WIT definition starting when systolic blood pressure is
      less than 50 mm Hg and finishing with cold arterial flush, provides the simplest,
      most universal definition that encompasses all important elements of warm
      ischemia. There is a need to prospectively collect data on all potential DCD lung
      donors and correlate these with clinical outcomes.

PMID- 19104407
TI  - Islet transplantation with alemtuzumab induction and calcineurin-free maintenance
      immunosuppression results in improved short- and long-term outcomes.
AB  - BACKGROUND: Only a minority of islet transplant recipients maintain insulin
      independence at 5 years under the Edmonton protocol of immunosuppression. New
      immunosuppressive strategies are required to improve long-term outcomes.
      MATERIALS AND METHODS: Three subjects with unstable type 1 diabetes mellitus
      underwent islet transplantation with alemtuzumab induction and sirolimus
      tacrolimus maintenance for 3 months and then sirolimus-mycophenolic acid
      maintenance thereafter. Follow-up was more than 2 years. Comparison was with 16
      historical subjects transplanted under the Miami version of the Edmonton
      protocol. RESULTS: Insulin independence was achieved in 2 of 3 alemtuzumab and 14
      of 16 historical subjects. Those who did not achieve insulin independence only
      received a single islet infusion. Insulin-independence rates remained unchanged
      in the alemtuzumab group, but decreased from 14 of 16 (88%) to 6 of 16 (38%) in
      the historical group over 2 years. Insulin requirements increased in the
      historical group while remaining stable in the alemtuzumab group. Comparison of
      functional measures at 3 months suggested better engraftment with alemtuzumab
      (P=NS). Further comparison of alemtuzumab versus historical groups, up to 24
      months, demonstrated significantly better: Mixed meal stimulation index (24
      months, 1.0+/-0.08 [n=3] vs. 0.5+/-0.06 pmol/mL [n=6], P<0.01), mixed meal peak C
      peptide (24 months, 5.0+/-0.5 [n=3] vs. 3.1+/-0.3 nmol/mL [n=6], P<0.05), HbA1c
      (24 months, 5.4+/-0.15 [n=3] vs. 6.3+/-0.12 pmol/mL [n=10], P<0.01).
      Administration of alemtuzumab was well tolerated. There was no increased
      incidence of infections in alemtuzumab subjects despite profound, prolonged
      lymphocyte depletion. CONCLUSIONS: Islet transplantation with alemtuzumab
      induction was well tolerated and resulted in improved short- and long-term
      outcomes. Further investigation is underway for validation.

PMID- 19104409
TI  - The impact of purinergic signaling on renal ischemia-reperfusion injury.
AB  - BACKGROUND: Adenosine provides renovascular protection in mouse models of
      ischemia-reperfusion injury (I/RI) through purinergic members of the G protein
      coupled receptor family, such as the adenosine 2A receptor (A2AR).
      Ectonucleotidases CD39 and CD73 are integral vascular and immune nucleotidases
      that regulate extracellular adenosine signaling. Current investigation of CD39
      and CD73 in renal I/RI has primarily focused on their respective roles in
      ischemic preconditioning. METHODS: In this study, we established a unilateral
      renal I/RI model and investigated the role of adenosine generation versus
      nucleotide removal in mediating protection in renal I/RI using mice deficient in
      CD39, CD73 or A2AR, thereby sequentially disrupting ectonucleotidase cascade and
      adenosinergic signaling. RESULTS: Compared with wild-type mice, Cd73 null mice
      showed reduced levels of serum creatinine and urea, apoptosis of renal cells, and
      histologic damage after I/RI. Deletion of CD39 was associated with severe renal
      injury. Administration of apyrase, a soluble form of CD39, decreased global
      apoptosis and I/RI induced renal injury in wild-type mice. Apyrase treatment also
      improved renal histology to some extent in A2AR null mice. CONCLUSION: The
      relative protective effect of CD73 deletion in renal I/RI may reflect an effect
      of AMP accumulation. Deletion of CD39 showed deleterious effects and
      administration of soluble CD39 exerted renal protection, which is partially
      mediated by A2AR. The protective effect conferred by apyrase suggests that
      supplementing CD39 NTPDase activity may be a useful therapeutic strategy in renal
      transplantation.

PMID- 19104410
TI  - Circulating markers of endothelial dysfunction interact with proteinuria in
      predicting mortality in renal transplant recipients.
AB  - BACKGROUND: Proteinuria is associated with endothelial dysfunction (ED) and
      increased mortality. We investigated whether urinary protein excretion (UPE) is
      correlated with markers of ED and whether these markers affect the association of
      proteinuria with mortality in renal transplant recipients (RTR). METHODS: Six
      hundred four RTR with a functioning graft for more than 1 year were included. RTR
      were divided according to UPE: less than 0.3, 0.3 to 1.0, and more than 1.0 g/24
      hr. Soluble intercellular adhesion molecule type 1 (sICAM-1) and soluble vascular
      cellular adhesion molecule type 1 (sVCAM-1) were measured using ELISA. RESULTS:
      UPE (0.2 [0.0-0.5] g/24 hr), sICAM-1 (603 (514-721) ng/mL), and sVCAM-1 (952 [769
      1196] ng/mL) were measured at 6.0 (2.6-11.4) years posttransplant. During follow
      up for 5.3 (4.7-5.7) years, 94 (16%) RTR died. UPE was correlated with sVCAM-1
      (standardized beta=0.13, P=0.001) but not with sICAM-1 (standardized beta=0.04,
      P=0.3). RTR with UPE more than 1.0 g/24 hr and high sICAM-1 (hazard ratio=4.7,
      95% confidence interval 2.3-9.7, P<0.0001) or sVCAM-1 (hazard ratio=4.2, 95%
      confidence interval 2.0-8.6, P=0.0001) concentrations were at increased risk for
      death, whereas RTR with UPE more than 1.0 g/24 hr and low concentrations of sICAM
      1 and sVCAM-1 were not. CONCLUSIONS: In RTR, UPE is correlated with sVCAM-1 but
      not with sICAM-1. Furthermore, RTR with proteinuria and high concentrations of
      sICAM-1 or sVCAM-1 have an increased risk for death, compared with RTR without
      proteinuria, whereas this is not the case in RTR with proteinuria but low
      concentrations of sICAM-1 and sVCAM-1. These results suggest that ED plays a role
      in the association of proteinuria with mortality after renal transplantation.

PMID- 19104411
TI  - Risk factors for human corneal graft failure within the Australian corneal graft
      registry.
AB  - BACKGROUND: Our aims were to examine graft survival and visual outcome after full
      thickness corneal transplantation. METHODS: Records of 18,686 penetrating corneal
      grafts, 14,622 with archival follow-up from 1 to 22 years, were examined within a
      national database. Kaplan-Meier survival analysis indicated variables of interest
      for Cox proportional hazards regression analysis. A model clustered by patient to
      control intereye or intergraft dependence was constructed to identify variables
      best predicting penetrating corneal graft failure. Visual acuity in the grafted
      eye was measured by Snellen acuity. RESULTS: Probability of corneal graft
      survival was 0.87, 0.73, 0.60, and 0.46 at 1, 5, 10, and 15 years, respectively.
      Reasons for graft failure included irreversible rejection (34%), corneal
      endothelial cell failure including cases of glaucoma (24%), and infection (14%).
      Variables predicting graft failure in multivariate analysis included transplant
      center, location and volume of surgeon's case-load, graft era, indication for
      graft, number of previous ipsilateral grafts, lens status, corneal
      neovascularization at transplantation, a history of ocular inflammation or raised
      intraocular pressure, graft diameter, and postoperative events including graft
      neovascularization and rejection. Best-corrected Snellen acuity of 6/12 or better
      was achieved by 45%, and of less than 6/60 by 26%, of grafted eyes at last follow
      up. CONCLUSIONS: The short-term survival of penetrating corneal transplants is
      excellent, but the eventual attrition rate appears inexorable and many factors
      that influence graft survival significantly are not amenable to change. Most
      penetrating grafts are performed for visual improvement, and excellent acuity
      will be achieved by approximately half of all grafts.

PMID- 19104412
TI  - Pediatric living donor kidney transplantation under alemtuzumab pretreatment and
      tacrolimus monotherapy: 4-year experience.
AB  - BACKGROUND: Alemtuzumab has been used in off-label studies of solid organ
      transplantation. METHODS: We analyzed the first 42 pediatric consecutive living
      donor kidney transplantations under alemtuzumab pretreatment with tacrolimus
      monotherapy and subsequent spaced weaning. We focused especially on the causes of
      recipient death and graft loss and the characteristics of rejection. RESULTS:
      Laparoscopic live-donor nephrectomy was associated with no mortality and no
      delayed graft function. The actuarial 1, 2, 3, and 4 years patient and graft
      survivals were 97.6% and 97.6%, 93.5% and 85.4%, 93.5% and 85.4%, and 93.5% and
      85.4%, respectively. The incidence of cumulative acute cellular rejection (ACR)
      at 1, 2, 3, and 4 years was 0%, 2.4%, 4.8%, and 4.8%, respectively. The mean
      serum creatinine (mg/dL) and glomerular filtration rate (mL/min/1.73 m) at 1, 2,
      and 3 years were 0.8+/-0.4 and 94.0+/-36.8, 0.9+/-0.4 and 79.6+/-31.9, and 0.9+/
      0.4 and 95.0+/-21.7, respectively. Two (4.7%) recipients had ACR, and both Banff
      1a ACRs were steroid sensitive. No patients had antibody-mediated rejection.
      Weaning to spaced dose (qod or less) tacrolimus monotherapy was attempted in 16
      (38%) and was successful in 12 (26%) patients. All patients are currently steroid
      free. There was no tissue invasive cytomegalovirus disease or infection, no
      BK/polyoma viral nephropathy, and no posttransplant proliferative disease.
      CONCLUSION: This experience confirms the 4-year safety and efficacy of this
      approach in pediatric recipients.

PMID- 19104413
TI  - 20-year follow-up results of a randomized controlled trial comparing
      antilymphocyte globulin induction to no induction in renal transplant patients.
AB  - BACKGROUND: The purpose of this study was to determine the impact of
      antilymphocyte globulin (ALG)-induction on long-term outcomes of postrenal
      transplantation. METHODS: Between January 1985 and January 1986, 123 consecutive
      renal transplants from deceased donors were performed at a single institution.
      Patients were randomized into two groups: group 1 (n=63, 40+/-10 year) received
      cyclosporine (CsA), prednisone, and azathioprine; and group 2 (n=60, 36+/-9 year)
      received ALG-induction, CsA, and prednisone and delayed initiation (45-90 days
      posttransplantation) of azathioprine if the CsA dose was less than 4 mg/kg per
      day. Target CsA trough levels were 150 to 250 ng/mL. Cytomegalovirus prophylaxis
      was not used. Human leukocyte antigen matching (2.4+/-1.1 vs. 2.6+/-1.2) and cold
      ischemia time (38+/-8 hr vs. 39+/-9 hr) did not differ. RESULTS: The incidence of
      acute rejection was lower in group 2 (28% vs. 75%, P<0.0001). The incidence of
      cytomegalovirus infection was 10% in group 1 and 18% in group 2 (P=0.41). The
      incidence of cancer was 22.2% in group 1 and 11.7% in group 2 (P=0.53) and the
      incidence of lymphoma did not differ (3% vs. 5%, P=0.77). Patient and graft
      survival in groups 1 and 2 at 1, 10, and 20 years were 100%/79% vs. 100%/93%,
      83%/56% vs. 88%/51%, and 64%/43% vs. 54%/47%, respectively (log-rank test, P=0.18
      and P=0.078). CONCLUSION: The use of ALG-induction resulted in a lower incidence
      of acute rejection and improved graft survival during the first year postrenal
      transplantation. Patient and graft survival at 20-year follow-up was not affected
      by ALG-induction.

PMID- 19104414
TI  - Donation patterns in four European countries: data from the donor action
      database.
AB  - BACKGROUND: To analyze heart-beating organ donation patterns in four countries
      using the Donor Action (DA) Program nationally and to identify areas for
      improvement. METHODS: Medical Record Review (MRR) of 18,118 critical care deaths
      between January 2006 and December 2007 in Belgium, Finland, France, and
      Switzerland. Data were entered to the DA System Database for analysis. RESULTS:
      Of 6561 patients without contraindications to donation, 45.3% met preconditions
      for brain death (BD) diagnosis, 31.4% had signs of severe brain damage and 28.8%
      met criteria for formal BD diagnosis. Belgium had the highest number of patients
      with formal BD diagnosis (75.7%) and Switzerland (57.4%, P<0.0001) the lowest.
      Although donor identification rates were uppermost in France (93.6%) and lowest
      in Finland (47.7%, P<0.0001); Finland excelled in donor referral (93.9% of
      identified cases) versus only 63.8% in Switzerland (P<0.0001), and excelled in
      family approach rates (92.7%) versus only 70.2% in France (P<0.0001). Consent
      rates were superior in Belgium and Finland and lowest in France (P<0.0001).
      Conversion rates (percent of potential donors vs. actual donors) were higher in
      France and Belgium and significantly lower in Finland and Switzerland (P=0.0187).
      Only Belgium had a non-heart-beating donation policy during the study period,
      resulting in 11.2% more donors added to the country's donor pool. CONCLUSIONS:
      The DA MRR proved to be an excellent tool to identify areas of improvement within
      certain steps of the donation process. Moreover, DA's MRR has shown to be
      applicable in different countries and environments and should be considered as a
      unique tool for comparing countries' donation performance.

PMID- 19104415
TI  - The development of a successful multiregional kidney paired donation program.
AB  - BACKGROUND: Kidney paired donation (KPD) is increasing the number of living donor
      transplants. Two major obstacles prevent moving KPD forward in the United States:
      (1) achieving a critical mass of pairs to efficiently find matches and (2)
      efficiently coordinating KPD transplants between multiple transplant centers. Two
      large regional programs, The New England Program for Kidney Exchange (NEPKE) and
      the Mid-Atlantic Paired Exchange Program (MAPEP) have developed a system of
      protocols to effectively increase the number of KPD transplants. METHODS:
      Incompatible pairs and nondirected donors (NDD) are referred to the system
      through transplant centers. Donor and recipient ABO, human leukocyte antigen, and
      recipient human leukocyte antigen antibody screening are used to determine
      potential matches. Utilization of a computer optimization algorithm matches pairs
      in two- and three-way exchanges, NDD chains, and list exchange chains. Team
      conference calls regarding transfer of information, crossmatches, surgery date,
      coordination of simultaneous donor nephrectomies, and other issues are
      coordinated as needed. RESULTS: Ten matches moved forward to donation and
      transplantation, and one is pending. Eight of these matches involved NDD chains,
      two 2-way exchanges, and 1 a list exchange chain. These matches resulted in 27
      transplants. Eighteen transplants occurred in NEPKE-only transplant centers, four
      in MAPEP-only centers, and an additional five were crossregional. CONCLUSION: The
      collaboration of NEPKE and MAPEP has demonstrated that crossregional coordination
      is feasible and expands the number of transplants performed beyond the capability
      of either program alone, especially when combined with computer optimization and
      multiple-type matches of three-way, NDD chains, and list exchange chains.

PMID- 19104416
TI  - Hurdles, barriers, and successes of a national living donor kidney exchange
      program.
AB  - BACKGROUND: Living donor kidney exchange is now performed in several countries.
      However, no information is available on the practical problems inherent to these
      programs. Here, we describe our experiences with 276 couples enrolled in the
      Dutch program. METHODS: Our protocol consists of five steps: registration,
      computerized matching, crossmatching, donor acceptation, and transplantation. We
      prospectively collected data of each step of the procedure. RESULTS: Of the 276
      registered pairs we created 183 computer-matched combinations. However, 62 of 183
      recipients proved to have a positive crossmatch with their new donor, which was
      not predicted by the screening results of the recipient centers. Alternative
      solutions were found for 39 couples, resulting in a total of 160 new combinations
      with negative crossmatches. Thereafter, because of 22 individual clinical
      problems, the exchange procedure had to be discontinued for 51 couples while only
      for 19 of them alternative solutions were found. At the end of day, 128 patients
      had received exchange kidneys, 55 were transplanted outside the program, 59 are
      still on the crossover waitlist, and 34 had left the program for medical or
      psychological reasons. CONCLUSION: A living donor kidney exchange program is a
      dynamic process. Many clinical hurdles and barriers are encountered that for a
      large part were not foreseen but should be taken into account when programs are
      initiated based on computer simulations. Success is dependent on a flexible
      organization able to create alternative solutions when problems arise.
      Centralized allocation and crossmatch procedures are instrumental in this
      respect.

PMID- 19104418
TI  - A multi-year analysis of islet transplantation compared with intensive medical
      therapy on progression of complications in type 1 diabetes.
AB  - BACKGROUND: We hypothesized that transplantation of islets into type 1 diabetics
      could improve outcomes of glucose metabolism, renal function, retinopathy, and
      neuropathy compared with intensive medical therapy. METHODS: We conducted a
      prospective, crossover, cohort study of intensive medical therapy (group 1)
      versus islet cell transplantation (group 2) in 42 patients. All were enrolled in
      group 1 then 31 crossed over with group 2 when islet donation became available.
      Transplantation was performed by portal venous embolization of more than 12,000
      islet equivalents/kg body weight under cover of immunosuppression with
      antithymocyte globulin, tacrolimus, and mycophenolate. Outcome measures were
      HbA1c, change in glomerular filtration rate (GFR), progression of retinopathy,
      and change in nerve conduction velocity. This report details interim analysis of
      outcomes after 34+/-18 months (group 1) and 38+/-18 months (group 2). RESULTS:
      HbA1c (%) in group 1 was 7.5+/-0.9 versus 6.6+/-0.7 in group 2 (P<0.01). GFR
      (mL/min/month) declined in both groups (group 1 -0.45+/-0.7 vs. group 2 -0.12+/
      0.7, P=0.1). Slope of the GFR decline in group 1 was significantly more than 0.
      Retinopathy progressed in 10 of 82 eyes in group 1 versus 0 of 51 in group 2
      (P<0.01). Nerve conduction velocity (m/sec) remained stable in group 1 (47.8+/-5
      to 47.1+/-5 m/sec) and group 2 (47.2+/-4.5 to 47.7+/-3.5). CONCLUSION: Islet
      transplantation yields improved HbA1c and less progression of retinopathy
      compared with intensive medical therapy during 3 years follow-up.

PMID- 19104417
TI  - Bortezomib provides effective therapy for antibody- and cell-mediated acute
      rejection.
AB  - BACKGROUND: Current antihumoral therapies in transplantation and autoimmune
      disease do not target the mature antibody-producing plasma cell. Bortezomib is a
      first in class proteosomal inhibitor, that is Food and Drug Administration
      approved, for the treatment of plasma cell-derived tumors that is multiple
      myeloma. We report the first clinical experience with plasma cell-targeted
      therapy (bortezomib) as an antirejection strategy. METHODS: Eight episodes of
      mixed antibody-mediated rejection (AMR) and acute cellular rejection (ACR) in six
      transplant recipients were treated with bortezomib at labeled dosing. Monitoring
      included serial donor-specific antihuman leukocyte antigen antibody (DSA) levels
      and repeated allograft biopsies. RESULTS: Six kidney transplant patients received
      bortezomib for AMR and concomitant ACR. In each case, bortezomib therapy provided
      (1) prompt rejection reversal, (2) marked and prolonged reductions in DSA levels,
      (3) improved renal allograft function, and (4) suppression of recurrent rejection
      for at least 5 months. Moreover, immunodominant DSA (iDSA) (i.e., the antidonor
      human leukocyte antigen antibody with the highest levels) levels were decreased
      by more than 50% within 14 days and remained substantially suppressed for up to 5
      months. One or more additional DSA were present at lower concentrations (non
      iDSA) in each patient and were also reduced to nondetectable levels. Bortezomib
      related toxicities (gastrointestinal toxicity, thrombocytopenia, and
      paresthesias) were all transient. CONCLUSIONS: Bortezomib therapy: (1) provides
      effective treatment of AMR and ACR with minimal toxicity and (2) provides
      sustained reduction in iDSA and non-iDSA levels. Bortezomib represents the first
      effective antihumoral therapy with activity in humans that targets plasma cells.

PMID- 19104419
TI  - Living-donor lobar lung transplantation for pulmonary complications after
      hematopoietic stem cell transplantation.
AB  - BACKGROUND: The indication of lung transplantation for patients with pulmonary
      complications of hematopoietic stem cell transplantation (HSCT) remains
      controversial, and only few such cases have been reported. We reviewed our
      experiences regarding living-donor lobar lung transplantation (LDLLT) in patients
      with pulmonary complications of HSCT. METHODS: We reviewed and assessed seven
      patients (age, 6-45 yr) who underwent LDLLT at Okayama University Hospital for
      pulmonary complications of HSCT (HSCT group). Their characteristics and
      postoperative results were compared with those of 41 LDLLT without HSCT patients
      (non-HSCT group). In the HSCT group, indications for LDLLT included bronchiolitis
      obliterans (n=6) and pulmonary fibrosis (n=1) that had developed after treatments
      involving HSCT. Preexisting hematologic diseases included acute lymphocyte
      leukemia (n=4), acute promyelocystic leukemia (n=1), myelodysplastic syndrome
      (n=1), and aplastic anemia (n=1). RESULTS: In the HSCT group, two patients died
      due to infectious complications, whereas five are currently alive (an overall
      survival of 71.4%) without any recurrence of the hematologic diseases (mean
      follow-up period, 35.7 months). The mean of acute rejection episodes was 1.1 per
      patient in the HSCT group and 1.8 in the non-HSCT group. One of the seven HSCT
      (14.4%) and 10 non-HSCT (24.4%) patients have currently developed bronchiolitis
      obliterans syndrome. CONCLUSION: Our results showed that LDLLT for patients with
      respiratory failure because of pulmonary complications of HSCT could be an
      effective approach with less rejection episodes; however, it has a possibly
      higher risk of the development of infectious complications.

PMID- 19104420
TI  - Safety and efficacy of statin therapy in patients switched from cyclosporine a to
      sirolimus after cardiac transplantation.
AB  - INTRODUCTION: Statins are an established therapy after cardiac transplantation.
      Sirolimus (Srl) has been used successfully in cardiac transplant patients.
      However, potential side effects are hyperlipidemia and interactions with statins.
      The aim of the study was to evaluate the safety and efficacy of statin therapy
      after switch to a Srl-based immunosuppression. PATIENTS AND METHODS: Ninety-eight
      long-term patients were switched from Cyclosporine A to Srl. Also all patients
      received mycophenolate mofetil alone or mycophenolate mofetil plus steroid
      therapy. Reasons for switch were renal dysfunction, graftvasculopathy, or skin
      cancer. Patients were switched 7.8+/-4.7 years after transplant. Total
      observation period was 12 months before and after switch, respectively. Safety
      evaluation consisted of regular measurements of CPK and liver enzymes to evaluate
      the incidence myopathy and hepatoxicity. Efficacy analysis was performed by
      serial blood lipid assessments (low-density lipoprotein, high-density
      lipoprotein, total cholesterol, and triglycerides). RESULTS: Forty-three
      percentage of patients received atorvastatin, 38% pravastatin, and 18% other
      drugs or therapy changes. Most lipid blood levels increased significantly after
      switch (cholesterol: 192.9+/-38.6 mg/dL vs. 221.8+/-49.2 mg/dL, P<0.0001; low
      density lipoprotein: 108.0+/-35.6 mg/dL vs. 123.8+/-37.9 mg/dL, P<0.0001; and
      triglycerides: 178.3+/-88.2 mg/dL vs. 225.5+/-139.1 mg/dL, P<0.0001). Blood lipid
      levels after switch were not associated with statin type. Overall safety was
      acceptable, although incidence of myopathy doubled after switch (n=20 vs. 40;
      P<0.01). However, most cases were asymptomatic CPK elevations in the pravastatin
      group. Hepatotoxicity rate was 4% and only temporary. CONCLUSION: Statin therapy
      after switch from cyclosporine A to Srl in long-term cardiac transplant patients
      is safe. However, regular testing of blood lipids and CPK should be mandatory.

PMID- 19104421
TI  - Pediatric intestinal retransplantation: techniques, management, and outcomes.
AB  - BACKGROUND: Intestinal retransplantation (Re-ITx) has historically been
      associated with high morbidity and mortality. METHODS: The outcomes of all
      children receiving Re-ITx between 1990 and 2007 at our center were reviewed.
      RESULTS: One hundred seventy-two children received primary intestinal grafts.
      Fourteen children (8.1%) were retransplanted with 15 grafts. Causes of graft
      failure were acute cellular rejection (ACR, n=4), liver failure (n=2), chronic
      rejection (n=3), posttransplant lymphoproliferative disorder (n=1), graft
      dysmotility or dysfunction (n=3), ACR with severe infection (n=1), and arterial
      graft aneurysm (n=1). Initial transplants were isolated bowel in nine, liver
      bowel in five, and one multivisceral. The mean time of initial graft survival was
      34.2 months. Re-ITx was with isolated bowel in two, liver-bowel in four, and
      multivisceral in nine (four with kidney). Initial immunosuppression was Tac-Pred
      based in nine and rabbit antithymocyte globulin-Tac based in six cases. Re-ITx
      was carried out under Tac-Pred in six, rabbit antithymocyte globulin-Tac in
      eight, and alemtuzumab monoclonal anti-CD52 antibody in one. Ten (71.4%) patients
      are alive with functioning grafts at a mean current follow-up time of 55.9
      months. Four patients died from posttransplant lymphoproliferative disorder,
      severe ACR, fungal sepsis, and bleeding from pseudoaneurysm, respectively, at a
      mean time of 5.7 months post-Re-ITx. All surviving patients weaned-off total
      parenteral nutrition at a median time of 32 days and 90% are off intravenous
      fluids. CONCLUSIONS: Improved long-term survival and outcome in pediatric Re-ITx
      may be attributed to improvements in initial immunosuppression protocols,
      technical modifications, proper timing, and improved infectious disease
      monitoring. Careful patient selection and posttransplant management are essential
      for successful long-term outcome.

PMID- 19104423
TI  - Pancreas transplant alone as an independent risk factor for the development of
      renal failure: a retrospective study.
AB  - BACKGROUND: Pancreas transplant alone (PTA) is a controversial procedure. Without
      clearly demonstrated patient survival, recipients report improved quality of
      life. Nephrotoxic immunosuppression (IS) may exacerbate diabetic renal injury
      post-PTA. METHODS: A single institution retrospective review of patients
      receiving PTA over a 14-year period was completed. Patient and donor
      demographics, surgical outcomes, rejection, and patient or graft survival were
      analyzed. Pre- and Postoperative estimated glomerular filtration rates (eGFR)
      were calculated based on the modification of diet and renal disease. Multivariate
      analysis was performed. RESULTS: One hundred twenty-three patients undergoing 131
      PTAs had an average age of 40.0 years. Seven patients were retransplanted and one
      received a third pancreas. Mean graft survival was 3.26 years (0-11.3 years) with
      21 patients (17%) lost to follow-up. One- and 5-year patient survivals were 96.6%
      and 91.5%, respectively (mean, 7.15 year). Seventeen patients had an eGFR less
      than 50 mL/min/1.73 m preoperatively, whereas 64 patients did so post-PTA and 24
      had an eGFR less than 30 mL/min. Mean eGFR pretransplantation was 88.9 vs. 55.6
      posttransplantation (P<0.0001) with mean follow-up of 3.68 years. All but 16
      (12%) patients showed a decrease in eGFR. Mean decrement was 32.1 mg/min/1.73 m.
      Thirteen developed end-stage renal disease chronic kidney disease (CKD 5)
      requiring kidney transplantation (KT) at a mean of 4.36 years. Eighty-three
      patients had an episode of rejection. In post-PTA RF, graft survival was 3.2 vs.
      2.4 years (P=0.13). In those requiring KT, graft survival was 7.9 vs. 2.9 years
      (P<0.0001). Cold ischemia times, donor age, and preoperative eGFR for those with
      and without RF-requiring KT were not significant. Body mass index was
      statistically significant. Leukocyte-depleting agents was evaluated, but was not
      significant. All patients received calcineurin inhibitor IS. CONCLUSIONS:
      Patients who undergo PTA may be at increased risk for RF. After comparing patient
      and donor demographics, IS, and human leukocyte antigen mismatch, it seems that
      PTA is an independent risk factor for the development of renal failure. Patients
      with more successful pancreatic grafts demonstrated lower eGFR. Patients should
      be made aware of the risks of long-term IS. Only the most appropriate patients
      should be chosen for PTA.

PMID- 19104424
TI  - Does interferon use prior to liver transplant influence hepatitis C outcomes
      following transplantation?
AB  - BACKGROUND: The most frequent reason for orthotopic liver transplantation (OLT)
      in the United States is due to complications of hepatitis C (HCV). Recent reports
      have shown decreased survival for HCV after OLT. Of note, the use of interferon
      (IFN) products has become wide spread with the majority of HCV patients being
      treated before transplant. AIM: To review the outcomes of HCV patients who have
      received IFN products before liver transplant compared with HCV patients those
      who have never received IFN. METHOD: Single-center, retrospective review of
      patients transplanted for HCV since December 1998 (n=131). Primary endpoint is
      the effect of IFN exposure before transplant on posttransplant outcomes. RESULTS:
      Patients receiving before transplant (pre-IFN group; n=45) had a more aggressive
      recurrence of HCV with earlier recurrence (181.1+/-236 days vs. 303.4+/- 327
      days; P=0.031), frequency of recurrence [41/45 (91.1%) vs. 62/86 (72.1%);
      P=0.013], and 1-year recurrence free survival [20% (+/-0.06) vs. 48.2% (+/-0.05);
      P=0.005]. Survival difference was noted in the pre-IFN group at 1 year and 3
      years [79.7% (+/-0.06) vs. 90.5% (+/-0.03); 65.7 (+/-0.08) vs. 75.9% (+/-0.05);
      P=0.05] when compared with patients not receiving IFN (n=86) before transplant.
      CONCLUSIONS: Based on this study, interferon use before transplant for the HCV
      patient indicates poor outcomes After OLT. Because of the increasing numbers of
      HCV patients coming to transplant, validation of these results should be of
      utmost importance.

PMID- 19104425
TI  - Islet autotransplant outcomes after total pancreatectomy: a contrast to islet
      allograft outcomes.
AB  - INTRODUCTION: Islet allografts are currently associated with a high rate of early
      insulin independence, but after 1 year insulin-independence rates rapidly decline
      for unclear reasons. In contrast, as shown here, islet autotransplants (IATs)
      show durable function and extended insulin-independence rates, despite a lower
      beta-cell mass. METHODS: IAT function was determined in 173 patients after total
      pancreatectomy at our center. Islet function was considered full in insulin
      independent patients, partial when euglycemic on once-daily long-acting insulin
      (all tested were C-peptide positive), and failed if on a standard diabetic
      regimen. Outcomes for autoislet recipients by Kaplan-Meier survival analysis were
      compared with those of alloislet recipients in the Collaborative Islet Transplant
      Registry. RESULTS: IAT function (full/partial combined) and insulin independence
      correlated with islet yield. Overall only 65% functioned within the first year,
      and only 32% were insulin independent, but of IATs that functioned initially
      (n=112), 85% remained so 2-years later, in contrast to 66% of allografts (n=262).
      Of IAT recipients who became insulin independent (n=55), 74% remained so 2-years
      later versus 45% of initially insulin-independent allograft recipients (n=154).
      Of IATs that functioned or induced insulin independence, the rates at 5 years
      were 69% and 47%, respectively. CONCLUSION: Islet function is more resilient in
      autografts than allografts. Indeed, the 5-year insulin-independence persistence
      rate for IATs is similar to the 2-year rate for allografts. Several factors
      unique to allocases are likely responsible for the differences, including donor
      brain death, longer cold ischemia time, diabetogenic immunosuppression, and auto-
      and alloimmunity. IAT outcomes provide a minimum theoretical standard to work
      toward in allotransplantation.

PMID- 19104422
TI  - 2008 Update from the Collaborative Islet Transplant Registry.
AB  - BACKGROUND: This report summarizes the primary efficacy and the safety outcomes
      of islet transplantation reported to the NIDDK and JDRF funded Collaborative
      Islet Transplant Registry (CITR), currently the most comprehensive collection of
      human-to-human islet transplant data. METHODS: CITR collects and monitors
      comprehensive data on allogeneic islet transplantation in North America, Europe,
      and Australia since 1999. RESULTS: As of April 2008, the CITR registry comprised
      325 adult recipients of 649 islet infusions derived from 712 donors. At 3 years
      post-first infusion, 23% of islet-alone recipients were insulin independent
      (II>or=2 weeks), 29% were insulin dependent with detectable C-peptide, 26% had
      lost function, and 22% had missing data. Seventy percent achieved II at least
      once, of whom 71% were still II 1 year later and 52% at 2 years. Higher number of
      infusions, greater number of total islet equivalents infused, lower pretransplant
      HbA1c levels, processing centers related to the transplant center, and larger
      islet size are factors that favor the primary outcomes. Protocols with daclizumab
      or etanercept during induction had higher rates of II and lower rates of function
      loss, which endorse the current approaches. Infusion-related adverse event
      incidence was 0.71 events/person-year (EPY) in year 1, whereas immunosuppression
      related adverse event incidence was 0.87 EPY, both declining to less than 0.21
      EPY thereafter. CONCLUSIONS: Clinical islet transplantation needs to be evaluated
      using the most clinically relevant endpoints such as glucose stabilization and
      severe hypoglycemia prevention. The cumulative results of the registry confirm
      the inarguably positive impact of islet transplantation on metabolic control in
      T1 diabetes.

PMID- 19104426
TI  - HOXB4 but not BMP4 confers self-renewal properties to ES-derived hematopoietic
      progenitor cells.
AB  - BACKGROUND: Achieving transplantation tolerance remains an unresolved clinical
      challenge. Although bone marrow transplantation (BMT) induces mixed chimerism
      that establishes transplantation tolerance, the preconditioning regimens required
      for BMT to succeed are too prohibitive for routine use. Recently, embryonic stem
      (ES) cells have emerged as a potential alternative cell source to bone marrow
      cells. However, it remains difficult to efficiently differentiate these cells
      into hematopoietic cells. Here, we tested whether bone morphogenetic protein-4
      (BMP-4)-treated or HOXB4-transduced ES-derived hematopoietic cells engraft
      permanently inducing long-term mixed chimerism. METHODS: Initially, 129 SvJ R1 ES
      cells (H-2) were treated with BMP-4 for 36 hr. The cells were phenotyped and
      polymerase chain reaction studies were performed. The robustness of mixed
      chimerism was tested using mixed lymphocyte cultures and skin grafts. Chimeric
      MRL (H-2) animals received grafts from 129SvJ (H-2), Balb/c (H-2) or class II (H
      2) donor mice, and graft survival was monitored. Additionally, HOXB4-transduced
      ES cells were shown to more efficiently differentiate into hematopoietic
      progenitor cells that engrafted in allogenic and syngeneic recipient mice.
      RESULTS: BMP-4 treatment induced Sca-1 expression and up-regulated HOXB4, BMP-4,
      and BMP receptor gene expressions. The cells induced transient mixed chimerism,
      whereas cells derived from HOXB4-transduced ES cells engrafted long term (>100
      days). CONCLUSIONS: Although BMP-4 promotes hematopoiesis of ES cells, its impact
      is only transient, whereas permanent ectopic expression of HOXB4 significantly
      confers self-renewal and long-term engraftment of ES-derived hematopoietic cells.
      This strategy could facilitate the establishment of an alternative source of
      hematopoietic cells that could induce transplantation tolerance.

PMID- 19104427
TI  - Effects of blocking the chemokine receptors, CCR5 and CXCR3, With TAK-779 in a
      rat small intestinal transplantation model.
AB  - BACKGROUND: The effect of blocking lymphocyte chemokine receptors with TAK-779
      was investigated using a rat intestinal transplantation model. METHODS: Dark
      Agouti rat small intestines were heterotopically transplanted into Lewis rats.
      The recipients were treated with TAK-779 (10 mg/kg per day) by subcutaneous
      injection. Graft survival, histologic changes, mixed lymphocyte reaction, and
      antibody production were examined. Furthermore, expression of the chemokine
      receptors on the graft-infiltrating lymphocytes in the mesenteric lymph node
      (MLN) and Peyer's patches (PP) were measured using fluorescence-activated cell
      sorter analysis. RESULTS: Average duration of survival was greater for group T
      (with TAK-779: 9.8+/-1.4) than group A (without TAK-779: 7.0+/-0.6). Histologic
      findings and immunohistochemistry of the graft were consistent with the prolonged
      survival in group T. In the fluorescence-activated cell sorter analysis, several
      CD4+ and CD8+ cells were significantly suppressed in the blood, spleen, and MLN
      of the recipient and in the PP of the graft on postoperative day (POD) 6, but
      recovered in recipient spleen and MLN by POD 9. However, double-staining of graft
      infiltrating lymphocytes in MLN and PP showed a significant reduction in the
      numbers of T cells expressing CCR5 and CXCR3 by POD 9. On the other hand, mixed
      lymphocyte reaction and cytokine production, and the antidonor antibody titer
      were suppressed on POD 6 but not on POD 9. CONCLUSION: TAK779 diminished not only
      the number of the graft-infiltrating cells and their expression of CCR5 and
      CXCR3, but also the total number of recipient T cells that play a role in graft
      rejection. Further exploration of these effects will provide the novel treatment
      of the intestinal transplantation.

PMID- 19104428
TI  - Ischemia- reperfusion injury and its influence on the epigenetic modification of
      the donor kidney genome.
AB  - BACKGROUND: In clinical transplantation, ischemia-reperfusion injury (I/RI)
      causes damage to DNA. We hypothesize that one form of damage is the demethylation
      of methylated cytosines in the donor genome caused by the oxidative environment
      created first by ischemia, and subsequently by reperfusion on transplantation.
      This study contributes to the understanding of how the short-lived and transient
      ischemic insult may influence chronic pathological changes that occur in clinical
      transplantation in the long term. METHODS: A model of I/RI and chronic rejection;
      Fisher to Fisher kidney transplant rendered cold-ischemic for 4 hr before
      transplantation, to induce antigen-independent chronic nephropathy over a 6-month
      period, was used. Tissue was assessed by histopathology and methylation by
      pyrosequencing analysis. RESULTS: An epigenetic map of the rat renal C3 promoter
      was produced, which identified methylated Cytosine phospho Guanine (CpG) sites
      coincident to cytokine response elements and nuclear factor kappa-light-chain
      enhancer of activated B cells (NF-kappaB) binding sites. Pyrosequencing analysis
      showed that the tissue that had undergone 4 hr ischemia and reperfusion developed
      aberrant demethylation of cytosines in putative regulatory sites within the C3
      promoter. CONCLUSION: These findings may describe a newly recognized phenomena in
      the field of transplantation. Aberrant demethylation has long been linked to the
      development of tumors, and our data suggest a similar mechanism of gene
      dysregulation that may be initiated by I/RI with acute and chronic effects. These
      data may contribute to a further understanding of how the short lived and
      transient ischemic insult influences chronic pathological changes that occur even
      in the absence of major histocompatibility complex disparity in transplantation.

PMID- 19104429
TI  - Repetitive gastric aspiration leads to augmented indirect allorecognition after
      lung transplantation in miniature swine.
AB  - INTRODUCTION: Lung transplant recipients with documented gastroesophageal reflux
      disease (GERD) are at increased risk for graft dysfunction. Here, we present the
      first large-animal model of gastric aspiration after allogeneic lung
      transplantation and some preliminary data demonstrating the effect of chronic
      aspiration on the direct and indirect pathways of allorecognition. METHODS: Left
      orthotopic lung transplants (n=3) were performed in miniature swine across a
      major histocompatibility complex class I disparity, followed by 12 days of high
      dose cyclosporine A. At the time of transplantation, a transtracheal catheter was
      placed at the carina, above the bronchial anastomosis. A gastrostomy tube was
      placed for daily aspiration of gastric contents. Subsequently, graft lungs were
      instilled with gastric aspirate daily (3 mL/hrX8 hr/day) for 50 days. Recipients
      were followed up with daily complete blood count, scheduled chest radiographs,
      and biopsies. In vitro studies, including cell-mediated lympholysis, mixed
      lymphocyte reactions, and peptide proliferation assays, were performed. Results
      from these three recipients were compared with those of historical controls (n=6)
      who were treated identically, except for the tracheal cannulation and simulated
      gastric aspiration. RESULTS: Two of the experimental animals were euthanized with
      nonviable lungs soon after the postoperative day 50 biopsy. In both cases the
      native lung was normal. The third animal survived over 180 days without the
      evidence of chronic rejection. After immunosuppressive treatment, all animals
      demonstrated donor-specific hyporesponsiveness by assays of direct alloresponse
      (cell-mediated lympholysis, mixed lymphocyte reaction). A significant response to
      synthetic donor-derived class I peptide, however, was seen in all animals. A more
      pronounced and diffuse response was seen in the animals rejecting their grafts.
      The historical controls showed medium-term graft survival with evidence of
      chronic rejection in the majority of animals, as previously reported. CONCLUSION:
      In a model of GERD after lung transplantation, a spectrum of clinical outcomes
      was observed. The in vitro data suggest that acid reflux enhances the indirect
      alloresponse to processed donor class I antigen, giving mechanistic insight into
      the manner in which GERD may be deleterious to the transplanted lung.

PMID- 19104430
TI  - Tolerance induction in a large-animal model using total lymphoid irradiation and
      intrathymic bone marrow.
AB  - BACKGROUND: Immunological unresponsiveness of T cells to alloantigen can be
      induced by intrathymic injection of donor-specific antigen in small-animal
      models. Intrathymic tolerance to vascularized grafts in large animals has not
      previously been reported. METHODS: Thirty-two dogs were allocated into dog
      leukocyte antigen DP locus allele (class II)-matched donor-recipient pairs.
      Female recipients were paired with male donors. Tissue typing was based on
      restriction fragment length polymorphism. Recipients were given 18 Gy total
      lymphoid irradiation in 16 fractions (1.125 Gy each) over 4 weeks. Thoracotomy
      after the 6th fraction permitted perithymic (n=4) or intrathymic (n=4) injection
      of donor bone marrow (BM) or intrathymic injection of saline (n=5). Another group
      received intravenous peripheral BM infusion (n=3). Fifty days postthoracotomy
      recipients underwent bilateral nephrectomy and donor-specific kidney
      transplantation. Acute rejection, suspected when serum creatinine was more than
      600 mumol/L or urea was more than 40 mmol/L, was confirmed histologically. Full
      thickness skin grafts followed more than 100 days posttransplantation. Tissue
      samples were taken for Y-chromosome polymerase chain reaction. RESULTS: One
      intrathymic (25%) and three perithymic (75%) BM recipients developed tolerance to
      renal allografts. Three intrathymic BM recipients rejected after 27, 32, and 54
      days and one perithymic BM recipient rejected after 42 days. All recipients given
      peripheral BM or saline had rejected by 29 and 38 days, respectively. All
      recipients surviving more than 100 days posttransplantation, accepted donor
      specific and rejected dog leukocyte antigen-DP locus allele (class II) identical
      third-party skin grafts. Polymerase chain reaction detected intrathymic but not
      hematopoietic chimerism in sex-mismatched pairs. CONCLUSIONS: Fractionated total
      lymphoid irradiation and perithymic or intrathymic donor-specific BM induced
      tolerance to renal and skin allografts without inducing hematopoietic chimerism.

PMID- 19104431
TI  - The presence of Foxp3 expressing T cells within grafts of tolerant human liver
      transplant recipients.
AB  - BACKGROUND: Some experimental transplant-tolerance models have shown that the
      presence of regulatory T cells within grafts is important for the development of
      tolerance (Tol). METHODS.: To determine if the presence of regulatory T cells
      correlates with graft acceptance in living-donor liver-transplantation tolerance,
      the expression of Foxp3 mRNA and the presence of CD4, CD8, and Foxp3 cells were
      quantified in biopsies from tolerant recipients by real-time polymerase chain
      reaction and by immunohistochemistry and immunofluorescent staining (Gr-Tol). The
      results were compared with biopsies from the recipients on maintenance
      immunosuppression (Gr-IS), grafts removed because of chronic rejection (Gr-CR),
      or normal liver (Gr-NL). RESULTS: The expression of Foxp3 mRNA in Gr-Tol was
      higher than that in Gr-IS (P=0.07) and Gr-NL (P<0.0001), but equivalent to that
      in Gr-CR. In Gr-Tol, Foxp3 cells were detectable within the clustered CD4 and CD8
      cells in the portal areas. Ninety-two percent of those Foxp3 cells were CD4,
      whereas 8% were CD8. The number of Foxp3 cells was significantly increased in Gr
      Tol, compared with that in Gr-IS (P<0.05), although the number of CD4 or CD8
      cells did not differ between the two. Foxp3 cells were hardly detectable in Gr-CR
      or -NL. CONCLUSIONS: This is the first report showing that CD4Foxp3 cells are
      present within grafts in a subset of tolerant patients after human liver
      transplantation. A prospective study is needed to elucidate whether the
      assessment of intragraft expression of Foxp3 protein, but not Foxp3 mRNA, can aid
      the identification of living-donor liver-transplantation recipients who can
      successfully withdraw IS.

PMID- 19104432
TI  - Late steroid withdrawal and cardiovascular events in kidney transplant
      recipients.
AB  - INTRODUCTION: Cardiovascular events (CVE) are the leading cause of mortality in
      kidney transplant recipients. The adverse effects of long-term therapy with
      steroids on cardiovascular risk have motivated increasing interest in steroid
      withdrawal (SW). The objective of this study was to compare the incidences of CVE
      and all-cause mortality between patients who had undergone SW at 1 year
      posttransplant and control patients who continued on steroids. METHODS: A cohort
      of 400 consecutive adult recipients of a kidney transplant between 1993 and 1998
      who qualified for late SW was studied. At 1 year posttransplant 188 patients
      underwent SW, whereas 212 patients continued on steroids. Cox proportional
      hazards analysis was used to estimate CVE (cardiac and cerebrovascular events)
      and all-cause mortality hazard ratios (HR) for patients who had undergone SW
      versus controls who continued on steroids beyond 1 year. RESULTS: The average
      follow-up was 61 months. There were 44 (11%) cardiac events, 18 (4.5%)
      cerebrovascular events, and 41 deaths (10.3%). The composite outcome of CVE and
      all-cause mortality was reached in 26 (13.8%) subjects who had undergone SW and
      50 (23.6%) controls (P=0.013). In adjusted analyses, SW was associated with
      decreased risk for the composite outcome (HR 0.46, 95% confidence interval [CI]
      0.28-0.76), cardiac events (HR 0.48, 95% CI 0.28-0.84), and all-cause mortality
      (HR 0.27, 95% CI 0.12-0.59). There was no association of SW with the risk for
      cerebrovascular events (HR 1.76, 95% CI 0.45-7.01). CONCLUSION: In this
      retrospective analysis, SW at 1 year posttransplant was associated with decreased
      risk for future CVE and all-cause mortality.

PMID- 19104433
TI  - C4d-positive interacinar capillaries correlates with donor-specific antibody
      mediated rejection in pancreas allografts.
AB  - BACKGROUND: The deposition of the complement split fragment C4d and its
      association with acute antibody-mediated rejection (AMR) in pancreas transplant
      (PTx) is not well defined. To characterize the deposition of C4d in PTx, we
      analyzed 27 PTx biopsies from 18 patients transplanted between 2004 and 2007 at
      the University of Wisconsin. METHODS: The presence of C4d was graded in
      interacinar capillaries (IAC), islets, interstitium, and small- and medium-size
      vessels. Sera obtained at the time or within 5 days of the biopsy were tested for
      antidonor-specific antibodies (DSA). RESULTS: 16 biopsies (59.26%) showed at
      least 5% C4d+ IAC (range 5%-90%). Of those, five biopsies (18.5%) revealed
      diffuse labeling (>50% C4d+ IAC) and 11 (40.74%) showed focal staining (5%-50%
      C4d+ IAC). C4d+ IAC (>5%) was significantly associated with the presence of
      strong DSA for class I or class II (P<0.018). C4d staining of the media or
      endothelium of small and medium-size vessels was a common finding in all biopsies
      without any association with DSA. Similarly, staining of islets and parenchymal
      interstitium was not statistically associated with AMR. The majority of patients
      received intravenous corticosteroid bolus and taper, with specific cases
      requiring thymoglobulin, IVIg, rituximab, or plasmapheresis. Forty-six percent of
      patients who demonstrated AMR returned to insulin therapy because of chronic
      graft damage and loss of C-peptide. CONCLUSION: Our findings support the
      potential role of C4d labeling of PTx biopsies in the diagnosis of AMR and
      emphasize the staining of IAC as a valuable histologic tool for the diagnosis.

PMID- 19104434
TI  - Association between donor MBL promoter haplotype and graft survival and the
      development of BOS after lung transplantation.
AB  - BACKGROUND: Lung transplantation is a well accepted therapy for end-stage lung
      disease, despite high mortality rates. Mortality after transplantation is mainly
      caused by allograft failure in the first years after transplantation. Mannose
      binding lectin (MBL), a recognition molecule of innate immunity, has been
      associated with transplant outcome in other solid organ transplantation. In this
      study, the effect of donor- and recipient-MBL genotype on lung transplant outcome
      was investigated. MATERIALS AND METHODS: All lung transplantations performed in
      our center, except from retransplantations and combined lung-liver or heart-lung
      transplantations, were included. Genotyping of the MBL2 variants (promoter: L/H,
      Y/X, and P/Q allele and exon 1: A/D, A/B, and A/C allele) was performed in donor
      and recipient DNA. Analyses on graft survival and the development of
      bronchiolitis obliterans syndrome were performed with Kaplan-Meier (log rank)
      survival analysis. RESULTS: Of the 277 included cases, DNA was available from 189
      donors and 200 recipients and genotyping of the promoter single nucleotide
      polymorphisms was successful in 184 donors and 198 recipients and of the exon 1
      single nucleotide polymorphisms in 181 donors and 193 recipients. Patients who
      received a graft from a donor with an X-allele had better graft survival
      (P=0.007) and bronchiolitis obliterans syndrome free survival (P=0.007).
      Recipient MBL genotype was not associated with transplant outcome. CONCLUSION:
      The donor X-allele, which corresponds to the LXPA haplotype is associated with
      superior lung transplant outcome. Our findings might prove to be important in
      finding ways to optimize outcome after lung transplantation.

PMID- 19104435
TI  - A virtual crossmatch protocol significantly increases access of highly sensitized
      patients to deceased donor kidney transplantation.
AB  - BACKGROUND: Patients with preexisting antihuman leukocyte antigen (HLA)
      antibodies (sensitized patients) are more likely to have a positive crossmatch
      with possible donors and have a lower likelihood of receiving a renal transplant
      with longer wait times. A virtual crossmatch protocol using solid-phase
      technology to determine the specificity of anti-HLA antibodies may improve the
      probability of identifying a crossmatch-negative compatible donor and increase
      access of sensitized patients to kidney transplantation. METHODS: A virtual
      crossmatch protocol was implemented on October 1, 2006 with solid-phase HLA
      antibody characterization for all sensitized patients on the waiting list.
      Transplant rates for the period from October 2006 to June 2008 were compared with
      Scientific Registry of Transplant Recipients (SRTR) data from 2006 to determine
      national transplant rates for sensitized patients. RESULTS: SRTR data for 2006
      showed that nationally 590 of 10,659 transplants (5.5%) were in-patients with
      panel reactive antibody (PRA) more than or equal to 80%. During 2006 to 2008,
      after initiation of the virtual crossmatch protocol, we performed 122 deceased
      donor kidney transplants, of which 15 (12.3%) sensitized patients (PRA>or=80%)
      received transplants (P=0.004 compared with SRTR national data), with 9 (7.4%)
      patients having a PRA more than 90%. The virtual crossmatch protocol was
      predictive of a negative-final crossmatch and eliminated the use of preliminary
      cross-matching with attendant cost savings of more than $100,000. CONCLUSION:
      Initiation of a virtual crossmatch protocol using solid-phase histocompatibility
      techniques significantly increased access of sensitized patients to kidney
      transplantation and was more cost effective. Usage of a virtual crossmatch may
      facilitate greater sharing of kidneys to improve access to transplantation for
      sensitized recipients.

PMID- 19104436
TI  - Noninvasive Tim-3 messenger RNA evaluation in renal transplant recipients with
      graft dysfunction.
AB  - BACKGROUND: Renal biopsies are usually needed to elucidate graft dysfunction. In
      this study, T-cell immunoglobulin domain, mucin domain mRNA expression in the
      peripheral blood leukocytes (PBL) and urinary cells (UC) were studied as a
      noninvasive method for the diagnosis of acute rejection (AR) of kidney transplant
      patients with dysfunction. METHODS: One hundred sixty biopsies were obtained from
      115 patients. Blood and urine samples were collected immediately before the
      biopsies. Histopathologic diagnoses were acute tubular necrosis with superimposed
      AR or acute tubular necrosis in patients with delayed graft function (DGF), and
      (AR), or calcineurin inhibitor nephrotoxicity (CIN), or interstitial fibrosis and
      tubular atrophy in patients with acute graft dysfunction (AGD). Fifteen protocol
      biopsies of stable grafts were used as controls. mRNA relative quantification was
      performed by real-time polymerase chain reaction. RESULTS: Gene expression in
      tissue, PBL, and UC was always higher in patients with AR than in patients with
      the other causes of graft dysfunction (P<0.001). Significant correlations of gene
      expression in different compartments were observed (P<0.001). The obtained
      diagnostic parameters were 100% accurate in the DGF group and, respectively, for
      blood and urine: sensitivity (87% and 84%); specificity (95% and 96%); positive
      predictive value (87% and 89%); negative predictive value (93% and 94%); and
      accuracy (91% and 93%) for the group of patients with AGD. CONCLUSION: T-cell
      immunoglobulin domain, mucin domain mRNA quantification by real-time polymerase
      chain reaction in PBL and UC of renal transplant patients undergoing DGF or AGD
      may become a useful tool for an accurate noninvasive diagnosis of AR.

PMID- 19104437
TI  - Dramatic prostate-specific antigen response with activated hemicellulose compound
      in metastatic castration-resistant prostate cancer.
AB  - Castration-resistant prostate cancer (CRPC) is an incurable disease with limited
      treatment options. Herbal supplements are unconventional treatments for a variety
      of diseases. Active hemicellulose compound (AHCC) is a Japanese supplement
      discovered by hybridizing several mushrooms used in traditional healing for the
      purpose of maintaining 'super immunity'. We report on a 66-year-old gentleman
      with CRPC with an excellent serologic response to AHCC. This case hypothesizes
      that AHCC may have potential activity against CRPC.

PMID- 19104438
TI  - Image subtraction facilitates assessment of volume and density change in ground
      glass opacities in chest CT.
AB  - OBJECTIVES: To study the impact of image subtraction of registered images on the
      detection of change in pulmonary ground-glass nodules identified on chest CT.
      MATERIALS AND METHODS: A cohort of 33 individuals (25 men, 8 women; age range 51
      75 years) with 37 focal ground-glass opacities (GGO) were recruited from a lung
      cancer screening trial. For every participant, 1 to 3 follow-up scans were
      available (total number of pairs, 84). Pairs of scans of the same nodule were
      registered nonrigidly and then subtracted to enhance differences in size and
      density. Four observers rated size and density change of the GGO between pairs of
      scans by visual comparison alone and with additional availability of a
      subtraction image and indicated their confidence. An independent experienced
      chest radiologist served as an arbiter having all reader data, clinical data, and
      follow-up examinations available. Nodule pairs for which the arbiter could not
      establish definite progression, regression, or stability were excluded from
      further evaluation. This left 59 and 58 pairs for evaluation of size and density
      change, respectively. Weighted kappa statistics (kappa w) were used to assess
      interobserver agreement and agreement with the arbiter. Statistical significance
      was tested with a kappa z-test. RESULTS: When the subtraction image was
      available, the average interobserver kappa w improved from 0.52 to 0.66 for size
      change and from 0.47 to 0.57 for density change. Average agreement with the
      arbiter improved from 0.61 to 0.76 for size change and from 0.53 to 0.64 for
      density change. The effect was more pronounced when observer confidence without
      the subtraction image was low: agreement improved from 0.26 to 0.57 and from 0.19
      to 0.47 in those cases. CONCLUSIONS: Image subtraction improves the evaluation of
      subtle changes in pulmonary ground-glass opacities and decreases interobserver
      variability.

PMID- 19104439
TI  - Semi-automated quantification of hepatic lesions in a phantom.
AB  - PURPOSE: Accurate measurement is crucial for the assessment of tumor dimensions
      to allow accurate evaluation of tumor response. Thus, the purpose of our study
      was to assess the accuracy of semi-automated RECIST and volumetric measurements
      of liver lesions in a liver phantom with different CT acquisition parameters.
      MATERIALS AND METHODS: A phantom of the upper abdomen with 14 hepatic lesions of
      different sizes (diameter: 12.0-40.0 mm), densities (45/180 HU at 120 kV), or
      alignment (vertical/transverse) was scanned with a 16-slice multidetector row
      computed tomography using varying tube currents (40/60/80/100/120/165mAs eff),
      reconstruction kernels (Siemens B20/30/40/50/70s), or slice thicknesses
      (1/2/3/4/5 mm). Longest axial diameter and volume of the 14 lesions were
      quantified using a semi-automated software tool (SyngoOncology, Siemens Medical
      Solutions, Forchheim, Germany) and compared with the known real longest axial
      diameter and volume values of the lesions. Absolute percentage errors (APE) were
      calculated. Degree of agreement in longest axial diameter and volume between
      software and real measurements was represented graphically in Bland-Altman plots
      and by corresponding concordance correlation coefficient. RESULTS: At standard
      soft tissue reconstruction kernel (Siemens B30s) and slice thickness (3 mm) mean
      absolute percentage error APE (concordance correlation coefficients) ranged
      between 6.93 and 14.27 (0.96 and 0.99) for longest axial diameter and between
      4.98 and 10.85 (0.99 and 1.00) for volume. At varying reconstruction kernels, APE
      values (concordance correlation coefficients) ranged between 7.92 and 8.31 (0.98
      and 0.99) for longest axial diameter and between 4.95 and 6.93 (1.00) for volume.
      Applying different slice sections APE values (concordance correlation
      coefficients) differed from 6.54 to 11.82 (0.97 and 0.99) for longest axial
      diameter and from 6.93 to 9.17 (1.00) for volume. CONCLUSIONS: Software
      quantification of longest axial diameter and volume of hepatic lesions in a
      phantom demonstrated a high correlation and accuracy under varying multidetector
      row computed tomography parameter.

PMID- 19104440
TI  - Retention of iodine and expression of biomarkers for renal damage in the kidney
      after application of iodinated contrast media in rats.
AB  - OBJECTIVE: Commercially available iodinated contrast media (CM) show
      significantly different physico-chemical properties. The relevance of the
      viscosity of CM may be underestimated as a contributing factor for clinically
      relevant renal failure as suggested by a large registry data analysis (Swedish
      registry study). The objective of this preclinical study is to assess differences
      of a low and high-viscous CM regarding their retention time in the kidney.
      Furthermore, we investigated the expression of marker genes for renal damage and
      hypoxia to evaluate a potential renal damage and hypoxia after application of
      iodinated CM. MATERIAL AND METHODS: After application of Iopromide 300 and
      Iodixanol 320 CM, the iodine concentration over time was determined using
      computed tomography and x-ray fluorescence analysis in healthy Han Wistar and
      renally impaired ZSF1 rats. The latter served as a model for age and diabetes
      related renal impairment. X-ray attenuation (Hounsfield units) in the renal
      cortex was analyzed by 2 independent blinded readers. Furthermore, the expression
      of kidney injury molecule 1 (Kim-1/Havcr1) and heme oxygenase I (HO-1/HMOX1) was
      measured by quantitative reverse transcription-polymerase chain-reaction.
      RESULTS: Computed tomography and x-ray fluorescence analysis in the kidneys of
      animals treated with Iodixanol revealed significantly prolonged retention of
      iodine in the kidney as compared with animals treated with Iopromide. This
      difference was even more pronounced in renally impaired rats. Twenty-four hours
      after Iodixanol treatment, significantly increased levels of Kim-1/Havcr1 and HO
      1/HMOX1 transcript levels were observed compared with the saline and Iopromide
      treatment. CONCLUSIONS: A prolonged retention of contrast media in the kidney was
      observed after administration of dimeric CM (Iodixanol 320). One possible
      explanation for this effect could be the high viscosity of the dimeric CM
      (Iodixanol 320) and the lack of dilution by osmotic diuresis. This prolonged
      exposure is possibly associated with higher renal toxicity as indicated by the
      elevated expression of biomarkers for hypoxia and renal injury.

PMID- 19104441
TI  - The proapoptotic BCL-2 homology domain 3-only protein Bim is not critical for
      acute excitotoxic cell death.
AB  - Prolonged and repetitive epileptic activity is causally linked to neuronal cell
      death in the brain and is most marked in vulnerable subfields of the hippocampus.
      The Bcl-2 family protein Bim, a proapoptotic member of the BCL-2 homology domain
      3-only subfamily, has been implicated as an important mediator of neuronal cell
      damage in various pathological conditions, although its role in epilepsy
      associated cell death is not understood. We performed intrahippocampal
      stereotaxic injections of the glutamate analog kainic acid as an in vivo model of
      acute excitotoxicity to assess neuronal injury in Bim-deficient and control wild
      type mice. A variety of cell death parameters including chromatin condensation,
      TdT-mediated dUTP nick end labeling, and caspase-3 activity was assessed. We
      found no differences in the extent of hippocampal neuronal death parameters
      between the 2 groups. Moreover, electroencephalographic recordings after kainic
      acid injection revealed indistinguishable patterns of seizure activity in Bim
      deficient and wild-type animals. These in vivo and histological data suggest that
      Bim is not critically involved in excitotoxicity-induced acute neuronal cell
      injury.

PMID- 19104442
TI  - Implantation of neurotrophic factor-treated sensory nerve graft enhances survival
      and axonal regeneration of motoneurons after spinal root avulsion.
AB  - We previously showed that motor nerves are superior to sensory nerves in
      promoting axon regeneration after spinal root avulsion. It is, however,
      impractical to use motor nerves as grafts. One potential approach to enhancing
      axonal regeneration using sensory nerves is to deliver trophic factors to the
      graft. Here, we examined the regulation of receptors for brain-derived
      neurotrophic factor, glial cell line-derived neurotrophic factor, ciliary
      neurotrophic factor, and pleiotrophin after root avulsion in adult rats. We then
      tested their survival-promoting and neuroregenerative effects on spinal
      motoneurons. The results showed that receptors for brain-derived neurotrophic
      factor and glial cell line-derived neurotrophic factor were upregulated and that
      these trophic factors promoted survival and axonal regeneration of motoneurons
      when they were injected into the sensory nerve graft before implantation. In
      contrast, receptors for ciliary neurotrophic factor and pleiotrophin were
      downregulated after avulsion. Ciliary neurotrophic factor did not promote
      survival and axonal regeneration, whereas pleiotrophin promoted axonal
      regeneration but not survival of injured spinal motoneurons. Our results suggest
      that infusion of trophic factors into sensory nerve grafts promote motoneuron
      survival and axonal regeneration. The technique is technically easy and is,
      therefore, potentially clinically applicable.

PMID- 19104443
TI  - Immunocytochemical detection of newly generated neurons in the perilesional area
      of cortical infarcts after intraventricular application of brain-derived
      neurotrophic factor.
AB  - The adult brain responds to focal infarction with proliferation of glial
      subpopulations. In addition, cells that express the immature neuronal marker
      doublecortin have been found consistently in the perileisonal zone. We
      investigated whether application of brain-derived neurotrophic factor (BDNF)
      would influence this perilesional proliferative response. Photothrombotic
      infarcts were induced in the sensorimotor forelimb and hindlimb cortex of adult
      rats. Brain-derived neurotrophic factor or vehicle was continuously infused
      intraventricularly for 2 weeks after the infarct using osmotic minipumps.
      Proliferating cells were labeled by daily intraperitoneal injections of
      bromodeoxyuridine during the first 2 weeks and were quantified at days 14 and 42
      using semiautomatic stereology. Triple immunofluorescence with antibodies against
      immature and mature neuronal and glial markers was used to identify the
      proliferating cell populations. On day 14 after intraventricular BNDF
      application, the numbers of doublecortin-positive cells were doubled in the
      perilesional zone. On day 42, BDNF-treated animals had a small number of mature
      neurons in these areas, whereas vehicle-treated controls did not. Behavioral
      analysis with a battery of sensorimotor tests revealed, however, that the
      alterations in the perilesional cellular response were not associated with an
      improved functional outcome.

PMID- 19104444
TI  - Early-onset familial lewy body dementia with extensive tauopathy: a clinical,
      genetic, and neuropathological study.
AB  - We describe a Spanish family in which 3 of 4 siblings had dementia with Lewy
      bodies, 2 of them starting at age 26 years and the other at 29 years. The father
      has recently been diagnosed with Lewy body disease, with onset at 77 years.
      Neuropathological examination of the brain of the index patient disclosed unusual
      features characterized by diffuse Lewy body disease and generalized
      neurofibrillary tangle pathology but with no amyloid deposits in any region.
      Moreover, Lewy body pathology colocalized with neurofibrillary tangles in most
      affected neurons. Mutation screening that included all coding exons of presenilin
      1 (PSEN1), presenilin 2 (PSEN2), alpha-synuclein (SNCA), beta-synuclein (SNCB),
      microtubule-associated protein tau (MAPT), leucine-rich repeat kinase 2 (LRRK2),
      glucocerebrosidase (GBA), and exons 16 and 17 of the amyloid precursor protein
      (APP) genes did not identify any mutation. Genome-wide single nucleotide
      polymorphism was performed in 4 family members and ruled out any pathogenic
      duplication or deletion in the entire genome. In summary, we report a unique
      family with pathologically confirmed early-onset dementia with Lewy bodies with
      widespread tau and alpha-synuclein deposition. The absence of mutations in genes
      known to cause Lewy body disease suggests that a novel locus or loci are
      implicated in this neurodegenerative disease.

PMID- 19104445
TI  - Gene, cell, and axon changes in the familial amyotrophic lateral sclerosis mouse
      sensorimotor cortex.
AB  - Lower motoneuron abnormalities have been extensively documented in the murine
      model of familial amyotrophic lateral sclerosis, whereas information on
      corticospinal neurons in these mice is very limited. We investigated 1) mRNA
      levels of inflammation-related molecules in the deep layers in which
      corticospinal neurons reside, 2) corticospinal neurons labeled from tracer
      injections in the corticospinal tract at the cervical level, 3) axonal damage
      revealed by beta-amyloid precursor protein accumulation, and 4) glial cell
      activation in the sensorimotor cortex of presymptomatic and end-stage superoxide
      dismutase (SOD)-1 (G93A) mice. We demonstrated induction of inflammatory gene
      transcripts in the deep layers, early and progressive shrinkage of corticospinal
      cell bodies and activation of surrounding astrocytes and microglia with
      upregulation of major histocompatibility complex class I antigen. Accumulation of
      beta-amyloid precursor protein in proximal axonal swellings indicating axonal
      injury was also evident at the terminal stage in the motor cortex and internal
      capsule. Glial and axon changes were not observed elsewhere in the cortex. These
      data reveal that the entire motor circuit is affected in this murine amyotrophic
      lateral sclerosis model as it is in human amyotrophic lateral sclerosis.
      Sensorimotor cortical inflammation and progressive corticospinal cell body and
      fiber damage may reflect transsynaptic signaling of damage from lower
      motoneurons.

PMID- 19104446
TI  - Sirtuin 1 reduction parallels the accumulation of tau in Alzheimer disease.
AB  - Aging and metabolism-related disorders are risk factors for Alzheimer disease
      (AD). Because sirtuins may increase the life span through regulation of cellular
      metabolism, we compared the concentration of sirtuin 1 (SIRT1) in the brains of
      AD patients (n = 19) and controls (n = 22) using Western immunoblots and in situ
      hybridization. We report a significant reduction of SIRT1 (messenger RNA [mRNA], 
      29%; protein, -45%) in the parietal cortex of AD patients, but not in the
      cerebellum. Further analyses in a second cohort of 36 subjects confirmed that
      cortical SIRT1 was decreased in AD but not in individuals with mild cognitive
      impairment. SIRT1 mRNA and its translated protein correlated negatively with the
      duration of symptoms (mRNA, r2 = -0.367; protein, r2 = -0.326) and the
      accumulation of paired helical filament tau (mRNA, r2 = -0.230; protein, r2 = 
      0.119), but weakly with insoluble amyloid-beta 42 (mRNA, r2= -0.090; protein, r2
      = -0.072). A significant relationship between SIRT1 levels and global cognition
      scores proximate to death was also found (r2= +0.09, p = 0.049). In contrast,
      cortical SIRT1 levels remained unchanged in a triple-transgenic animal model of
      AD. Collectively, our results indicate that loss of SIRT1 is closely associated
      with the accumulation of amyloid-beta and tau in the cerebral cortex of persons
      with AD.

PMID- 19104447
TI  - Nuclear TAR DNA binding protein 43 expression in spinal cord neurons correlates
      with the clinical course in amyotrophic lateral sclerosis.
AB  - TAR DNA binding protein 43 (TDP-43) has been considered a signature protein in
      frontotemporal dementia and amyotrophic lateral sclerosis (ALS), but not in ALS
      associated with the superoxide dismutase 1 (SOD1) gene mutations (ALS1). To
      clarify how TDP may be involved in ALS pathogenesis, clinical and pathological
      features in cases of sporadic ALS ([SALS] n = 18) and ALS1 (n = 6) were analyzed.
      In SALS patients with rapid clinical courses, TDP mislocalization (i.e.
      cytoplasmic staining and TDP-positive cytoplasmic inclusions) in anterior horn
      cells was frequent. In SALS patients with slow clinical courses, TDP-43
      mislocalization was rare. In an ALS1 patient with the SOD1 gene mutation C111Y,
      there were numerous TDP-positive inclusions and colocalization of SOD1 and TDP.
      In mutant SOD1 transgenic (G93A) mice at the end stage (median, 256 days), TDP
      positive inclusions and TDP colocalization with SOD1 were also observed; nuclear
      TDP-43 immunoreactivity was highly correlated with life span in these mice. In
      both humans and mice, nuclei that stained strongly for TDP were large and
      circular; weakly stained nuclei were atrophic or deformed. In conclusion, low
      levels of TDP expression in the nucleus cor relate with a rapid clinical course
      in SALS and in ALS1 model mice, suggesting that nuclear TDP may play a protective
      role against motor neuron death resulting from different underlying etiologies.

PMID- 19104449
TI  - 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) does not elicit long-lasting
      increases in cyclooxygenase-2 expression in dopaminergic neurons of monkeys.
AB  - To elucidate the role of the prostaglandin synthase cyclooxygenase-2 (Cox-2) and
      the mechanisms of dopaminergic (DA) neurodegeneration, monkeys were injected
      subacutely or chronically (n = 5/group) with 1-methyl-4-phenyl-1,2,3,6
      tetrahydropyridine. Chronically treated animals developed parkinsonian signs and
      were killed 6 months after the last treatment; tyrosine hydroxylase-expressing
      neurons decreased in all substantia nigra (SN) cell groups in both treatment
      groups. In untreated controls (n = 3), there was low Cox-2 expression in ventral
      SN DA neurons and high expression in ventral tegmental area neurons. In
      subacutely treated monkeys, Cox-2 expression increased in surviving DA cells,
      particularly in the ventrolateral SN. In chronically treated monkeys, enhanced
      Cox-2 expression appeared only in surviving ventral tegmental area and ventral SN
      neurons. Thus increased Cox-2 did not persist in other SN neurons after
      discontinuing 1-methyl-4-phenyl-1,2,36-tetrahydropyridine. Some DA neurons in
      treated but not control monkeys expressed the active nuclear form of phospho-c
      Jun, but not the active form of nuclear factor-kappaB. We conclude that Cox-2
      expression does not confer vulnerability to neurodegeneration in DA neurons and
      that it is unlikely that a subacute insult to DA neurons can perpetuate
      degeneration through Cox-2 activation. Other mechanisms, probably through the Jun
      N-terminal kinase cascade, lead to DA cell death in this model.

PMID- 19104448
TI  - Neuropathology and cognitive impairment in Alzheimer disease: a complex but
      coherent relationship.
AB  - Amyloid plaques and neurofibrillary tangles (NFTs) are the pathological hallmarks
      of Alzheimer disease (AD). There is controversy regarding the use of current
      diagnostic criteria for AD and whether amyloid plaques and NFTs contribute to
      cognitive impairment. Because AD is specific to humans, rigorous and
      comprehensiveclinicopathologic studies are necessary to test and refine
      hypotheses of AD diagnosis and pathogenesis. Neither the clinical nor the
      pathological aspects of AD evolve in a linear manner, but thepredictable sequence
      of AD pathology allows for stage-based correlations with cognitive deterioration.
      We discuss subsets of patients with clinical dementia who lack amyloid plaques
      and NFTs and, conversely, whether individuals without antemortem cognitive
      impairment can harbor severe AD-type pathological findings at autopsy. There are
      many medical, technical, and anatomical challenges to clinicopathologic studies
      in AD. For example, at least two thirds of persons older than 80 years have non
      AD brain diseases that can effect on cognitive function. We argue that existing
      data strongly support the hypothesis that both amyloid plaques and NFTs
      contribute to cognitive impairment.

PMID- 19104450
TI  - Frequent infection of cerebellar granule cell neurons by polyomavirus JC in
      progressive multifocal leukoencephalopathy.
AB  - Progressive multifocal leukoencephalopathy (PML) occurs most often in
      immunosuppressed individuals. The lesions of PML result from astrocyte and
      oligodendrocyte infection by the polyomavirus JC (JCV); JCV has also been shown
      to infect and destroy cerebellar granule cell neurons (GCNs) in 2 human
      immunodeficiency virus (HIV)-positive patients. To determine the prevalence and
      pattern of JCV infection in GCNs, we immunostained formalin-fixed paraffin
      embedded cerebellar samples from 40 HIV-positive and 3 HIV-negative PML patients
      for JCV, and glial and neuronal markers. The JCV infection was detected in 30
      patients (70%); 28 (93%) of them had JCV-infected cells in the GC layer; JCV
      infected GCNs were demonstrated in 15 (79%) of 19 tested cases. The JCV
      regulatory T antigen was expressed more frequently and abundantly in GCNs than
      JCV VP1 capsid protein. None of 37 HIV-negative controls but 1 (3%) of 35 HIV
      positive subjects without PML had distinct foci of JCV-infected GCNs. Thus, JCV
      infection of GCNs is frequent in PML patients and may occur in the absence of
      cerebellar white matter demyelinating lesions. The predominance of Tantigen over
      VP1 expression in GCNs suggests that they may be the site of early or latent
      central nervous system JCV infection. These results indicate that infection of
      GCNs is an important, previously overlooked, aspect of JCV pathogenesis in
      immunosuppressed individuals.

PMID- 19104451
TI  - Diagnostic value of melanoma inhibitory activity serum marker in the follow-up of
      patients with stage I or II cutaneous melanoma.
AB  - In the follow-up of melanoma patients, there is still a need for an optimal serum
      marker to discover recurrent disease at an early stage. Melanoma inhibitory
      activity (MIA) has been investigated as a serum marker for cutaneous melanomas.
      Although the prognosis for melanoma based on stage is generally good, the disease
      identified at later stages is associated with high levels of morbidity and
      mortality. The value of MIA testing in early-stage melanoma was the goal of this
      study. Five thousand three hundred and thirty-four MIA serum values from 1079
      consecutive melanoma patients in stages I and II were obtained during routine
      follow-up at scheduled intervals. Sensitivity and specificity of MIA were
      calculated. The area under the receiver-operating characteristics curve and
      Somers' Dxy rank correlation were assessed. Metastasis occurred in 137 patients
      with a sensitivity of MIA testing of 67.6% in stage I and 65.6% in stage II
      patients. The specificity was 76.9% for stage I and 66.7% for stage II patients.
      The most reliable normal upper limit for MIA was redefined at 12.0 ng/ml, when
      compared with 8.8 and 15.0 ng/ml. Multivariate analysis revealed significantly
      more frequent false-positive values in elderly women and in men with an increased
      Breslow thickness.MIA adapted with a new cut-off level is then a useful serum
      marker even in the follow-up of not yet relapsed early-stage melanoma patients.
      In older women and in men with an increased tumor thickness, the higher rate of
      false-positive values should be considered before starting further diagnostics.
      Additional prospective studies to clarify the clinical combination with other
      serum markers seem promising.

PMID- 19104452
TI  - Prospective monitoring of adjuvant treatment in high-risk melanoma patients:
      lactate dehydrogenase and protein S-100B as indicators of relapse.
AB  - At present there is no international consensus on laboratory testing during the
      follow-up of melanoma patients. We carried out a prospective monitoring study on
      the usefulness of lactate dehydrogenase (LDH) and protein S-100B assessment in
      high-risk melanoma patients. Ninety-seven patients treated within prospective
      randomized trials on the adjuvant treatment of melanoma received quarterly
      clinical visits and blood examinations. During the median observation period of
      30 months disease progression was observed in 52 of 97 patients (53.1%). The
      clinical course of melanoma was correlated to elevated LDH and S-100B serum
      concentrations. The comparative analysis revealed that (i) neither LDH nor S-100B
      were indicators of in-transit metastases, (ii) clinically apparent lymph nodes
      were rarely detected because of elevated S-100B (29.4%) or LDH (11.8%) only, and
      (iii) the S-100B assessment was superior to LDH in the identification of early
      distant metastasis (53.8 vs. 23.1%; P=0.008). The rate of false-positive
      (elevated) LDH-serum levels and S-100B-serum levels in clinically disease-free
      melanoma patients did not differ significantly (S-100B 1.9% vs. LDH 1.6%). Our
      data indicate that only protein S-100B might be used as a highly specific and
      relatively sensitive marker of early distant metastasis. Both markers, LDH and S
      100B, are not able to identify loco-regional metastases with a low tumor load in
      high-risk melanoma patients.

PMID- 19104453
TI  - Functional recruitment of visual cortex for sound encoded object identification
      in the blind.
AB  - Individuals using a visual-to-auditory sensory substitution device (SSD) called
      'The vOICe' can identify objects in their environment through images encoded by
      sound. We have shown that identifying objects with this SSD is associated with
      activation of occipital visual areas. Here, we show that repetitive transcranial
      magnetic stimulation (rTMS) delivered to a specific area of occipital cortex
      (identified by functional MRI) profoundly impairs a blind user's ability to
      identify objects. rTMS delivered to the same site had no effect on a visual
      imagery task. The task and site-specific disruptive effect of rTMS in this
      individual suggests that the cross-modal recruitment of occipital visual areas is
      functional in nature and critical to the patient's ability to process and decode
      the image sounds using this SSD.

PMID- 19104454
TI  - Acupuncture reveals no specific effect on primary auditory cortex: a functional
      magnetic resonance imaging study.
AB  - Although acupuncture is effective in the treatment of several clinical
      conditions, its specificity has been questioned. We studied the effects of needle
      stimulation applied to 'ear-specific' acupuncture point GB43 on activations in
      primary auditory cortex using functional magnetic resonance imaging in comparison
      with sham acupuncture. Twenty healthy volunteers participated in this cross-over
      investigation. Multi-subject analysis showed no significant activations in the
      gyrus of Heschl during stimulation of the GB43 point or a sham point. In single
      subject analysis, activation within the primary auditory cortex was seen in two
      out of 20 volunteers. We found no evidence for specificity of acupuncture point
      GB43 in relation to primary auditory activation, previously suggested by two
      independent research groups.

PMID- 19104455
TI  - Discrimination of behaviorally irrelevant auditory stimuli in stage II sleep.
AB  - In sleep, the brain responds to significant stimuli such as one's own name or
      loud tones. It is, however, not yet known whether in sleep, the brain's response
      can vary systematically with change in an irrelevant stimulus. Here, we varied
      the intensity of a 1000 Hz tone and recorded the neural response of the
      participants by using electroencephalography. The P200 component of the auditory
      evoked potential increased linearly and significantly with intensity in wake and
      in stage II sleep. Pattern classification confirmed that there is information
      about tone intensity in the poststimulus period, especially in the period
      corresponding to the P200. The sleeping brain is capable of discriminating the
      fine aspects of a stimulus that is of no significance to the individual.

PMID- 19104456
TI  - Interretinal transduction of injury signals after unilateral optic nerve crush.
AB  - In this study, we report that partial unilateral optic nerve crush in the rat
      affects the number of retinal ganglion cells of the contralateral eye still in
      continuity with the ipsilateral superior colliculus. The reduction in cell number
      of the uncrossed retinal projection was accompanied by a microglia response and
      could be prevented by the local intravitreal application of the anti-inflammatory
      agent dexamethasone. Interestingly, the level of neuronal activity after optic
      nerve crush as evidenced by thallium autometallography was enhanced in the
      termination area of the uncrossed projection, the rostro-medial superior
      colliculus, suggesting that a dying-back mechanism is not involved. We propose
      that injury signals from the damaged optic nerve and retina are transduced to the
      unaffected eye.

PMID- 19104457
TI  - Early age-related changes in episodic memory retrieval as revealed by event
      related potentials.
AB  - Familiarity is better preserved than recollection in ageing. The age at which
      changes first occur and the slope of the subsequent decline, however, remain
      unclear. In this study, we investigated changes in episodic memory, by using
      event-related potentials (ERPs) in young (m=24), middle-aged (m=58) and older
      (m=70) adults. Although behavioural performance did not change before the age of
      65 years, changes in ERP correlates were already present in the middle-aged
      adults. The ERP correlates of recollection and monitoring processes were the
      first to be affected by ageing, with a linear decrease as age increased.
      Conversely, the ERP correlate of familiarity remained unchanged, at least up to
      the age of 65 years. These results suggest a differential time course for the age
      effects on episodic retrieval.

PMID- 19104458
TI  - Atypical interhemispheric communication in left-handed individuals.
AB  - The relative latencies of evoked electroencephalogram potentials to lateralized
      visual stimuli were used to calculate the interhemispheric transfer time (IHTT)
      in right-handed and left-handed males. We confirmed earlier observations of a
      directional asymmetry in right-handed males. That is, IHTT from the right to the
      left hemisphere is significantly shorter than from the left to the right. We
      showed for the first time, however, that this directional asymmetry is not seen
      in left-handed males. It is suggested that differences in the cytoarchitechtonics
      of the right and left hemisphere (differences that may result in lateralization
      of function per se) underlie the asymmetric IHTT in right handers, and that these
      differences are less pronounced in left handers.

PMID- 19104459
TI  - Long-term meditation is associated with increased gray matter density in the
      brain stem.
AB  - Extensive practice involving sustained attention can lead to changes in brain
      structure. Here, we report evidence of structural differences in the lower
      brainstem of participants engaged in the long-term practice of meditation. Using
      magnetic resonance imaging, we observed higher gray matter density in lower brain
      stem regions of experienced meditators compared with age-matched nonmeditators.
      Our findings show that long-term practitioners of meditation have structural
      differences in brainstem regions concerned with cardiorespiratory control. This
      could account for some of the cardiorespiratory parasympathetic effects and
      traits, as well as the cognitive, emotional, and immunoreactive impact reported
      in several studies of different meditation practices.

PMID- 19104460
TI  - Interaction between PON1 and population density in amyotrophic lateral sclerosis.
AB  - Paraoxonase polymorphisms have been associated with amyotrophic lateral sclerosis
      (ALS). Paraoxonases are detoxifying enzymes involved in the metabolism of
      organophosphates. We tested the hypothesis that genetic variation within
      paraoxonase genes would interact with the environmental exposure to paraoxonase
      substrates. We used population density in the location of residence of ALS
      patients as a surrogate marker for environmental exposure. Paraoxonase genotypes
      at previously associated single nucleotide polymorphisms rs662, rs854560,
      rs6954345, and rs11981433 were studied in 98 patients from the South East England
      ALS population-based register. A case-only analysis was carried out and median
      population density was used to categorize patients into rural or urban
      environments. We found a significant interaction with population density for
      marker rs854560 (L55M) in ALS.

PMID- 19104461
TI  - NEI releases complete data from Age-Related Eye Disease Study.

PMID- 19104462
TI  - A farsighted view of myopia.

PMID- 19104463
TI  - 2008 EFCLIN Award presented to Academy of Optometry's Joseph Barr.

PMID- 19104465
TI  - Prevalence of myopia in urban and rural children in mainland China.
AB  - It has been well recognized that myopia more likely affects East Asians,
      particularly the Japanese and Chinese population. Although some studies have
      reported the prevalence of myopia in children living in mainland China, most of
      these studies are based on subjects with unknown representativeness, non-uniform
      definition, and measurement methods. A higher prevalence of myopia in urban
      settings, compared with rural settings, has been consistently suggested in
      several studies. This article intends to review the available data on the
      prevalence of myopia in Chinese children living in China; particular
      consideration is given to the evidence of urban-rural differences and their
      implications.

PMID- 19104464
TI  - Imposed anisometropia, accommodation, and regulation of refractive state.
AB  - PURPOSE: To determine the effects of imposed anisometropic retinal defocus on
      accommodation, ocular growth, and refractive state changes in marmosets. METHODS:
      Marmosets were raised with extended-wear soft contact lenses for an average
      duration of 10 weeks beginning at an average age of 76 d. Experimental animals
      wore either a positive or negative power contact lens over one eye and a plano
      lens or no lens over the other. Another group wore binocular lenses of equal
      magnitude but opposite sign. Untreated marmosets served as controls and three
      wore plano lenses monocularly. Cycloplegic refractive state, corneal curvature,
      and vitreous chamber depth were measured before, during, and after the period of
      lens wear. To investigate the accommodative response, the effective refractive
      state was measured through each anisometropic condition at varying accommodative
      stimuli positions using an infrared refractometer. RESULTS: Eye growth and
      refractive state are significantly correlated with the sign and power of the
      contact lens worn. The eyes of marmosets reared with monocular negative power
      lenses had longer vitreous chambers and were myopic relative to contralateral
      control eyes (p < 0.01). Monocular positive power lenses produced a significant
      reduction in vitreous chamber depth and hyperopia relative to the contralateral
      control eyes (p < 0.05). In marmosets reared binocularly with lenses of opposite
      sign, we found larger interocular differences in vitreous chamber depths and
      refractive state (p < 0.001). Accommodation influences the defocus experienced
      through the lenses, however, the mean effective refractive state was still
      hyperopia in the negative-lens-treated eyes and myopia in the positive-lens
      treated eyes. CONCLUSIONS: Imposed anisometropia effectively alters marmoset eye
      growth and refractive state to compensate for the imposed defocus. The response
      to imposed hyperopia is larger and faster than the response to imposed myopia.
      The pattern of accommodation under imposed anisometropia produces effective
      refractive states that are consistent with the changes in eye growth and
      refractive state observed.

PMID- 19104466
TI  - Biomechanics of the sclera in myopia: extracellular and cellular factors.
AB  - PURPOSE: Excessive axial elongation of the eye is the principal structural cause
      of myopia. The increase in eye size results from active remodelling of the
      sclera, producing a weakened scleral matrix. The present study will detail the
      biomechanics of the sclera and highlight the matrix and cellular factors
      important in the control of eye size. METHODS: Scleral elasticity (load vs.
      tissue extension) and creep rate (tissue extension vs. time) have been measured
      postmortem in human eyes. Animal models of myopia have allowed the direct
      relevance of scleral biomechanics to be investigated during myopia development.
      Recently, data on tissue matrices incorporating scleral fibroblasts have
      highlighted the role of cellular contraction in scleral biomechanics. RESULTS:
      Scleral elasticity is increased in eyes developing myopia, with a reduction in
      the failure load of the tissue. Scleral creep rate is increased in the sclera
      from eyes developing myopia, and reduced in eyes recovering from myopia. These
      changes in biomechanical properties of the sclera occur early in the development
      of myopia (within 24 h). Alterations in scleral biomechanics during myopia
      development have been attributed to changes in matrix constituents, principally
      reduced collagen content. Although the biochemical structure of the sclera plays
      a critical role in defining the mechanical properties, recent studies
      investigating the cellular mechanics of the sclera, implicate myofibroblasts in
      scleral biomechanics. Scleral myofibroblasts have the capacity to contract the
      matrix and are regulated by tissue stress and growth factors such as transforming
      growth factor-beta. Changes in these regulatory factors have been observed during
      myopia development, implicating cellular factors in the resultant weakened
      sclera. CONCLUSIONS: Changes in the biomechanical properties of the sclera are
      important in facilitating the increase in axial length that results in myopia.
      Understanding the matrix and cellular factors contributing to the weakened sclera
      may aid in the development of a clinically appropriate treatment for myopia.

PMID- 19104468
TI  - What's hot in myopia research-The 12th International Myopia Conference,
      Australia, July 2008.

PMID- 19104471
TI  - HLA-B*3505 allele is a strong predictor for nevirapine-induced skin adverse drug
      reactions in HIV-infected Thai patients.
AB  - OBJECTIVE: Investigation of a possible involvement of differences in human
      leukocyte antigens (HLA) in the risk of nevirapine (NVP)-induced skin rash among
      HIV-infected patients. METHODS: A step-wise case-control association study was
      conducted. The first set of samples consisted of 80 samples from patients with
      NVP-induced skin rash and 80 samples from NVP-tolerant patients. These patients
      were genotyped for the HLA-A, HLA-B, HLA-C, HLA-DRB1, HLA-DQB1, and HLA-DPB1 by a
      sequence-based HLA typing method. Subsequently, we verified HLA alleles that
      showed a possible association in the first screening using an additional set of
      samples consisting of 67 cases with NVP-induced skin rash and 105 controls.
      RESULTS: An HLA-B*3505 allele revealed a significant association with NVP-induced
      skin rash in the first and second screenings. In the combined data set, the HLA
      B*3505 allele was observed in 17.5% of the patients with NVP-induced skin rash
      compared with only 1.1% observed in NVP-tolerant patients [odds ratio (OR)=18.96;
      95% confidence interval (CI)=4.87-73.44, Pc=4.6x10] and 0.7% in general Thai
      population (OR=29.87; 95% CI=5.04-175.86, Pc=2.6x10). The logistic regression
      analysis also indicated HLA-B*3505 to be significantly associated with skin rash
      with OR of 49.15 (95% CI=6.45-374.41, P=0.00017). CONCLUSION: A strong
      association between the HLA-B*3505 and NVP-induced skin rash provides a novel
      insight into the pathogenesis of drug-induced rash in the HIV-infected
      population. On account of its high specificity (98.9%) in identifying NVP-induced
      rash, it is possible to utilize the HLA-B*3505 as a marker to avoid a subset of
      NVP-induced rash, at least in Thai population.

PMID- 19104467
TI  - Molecular genetics of human myopia: an update.
AB  - Myopia, or nearsightedness, is the most common human eye disorder in the world,
      and is a significant global public health concern. Along with cataract, macular
      degeneration, infectious disease, and vitamin A deficiency, myopia is one of the
      most important causes of visual impairment worldwide. Severe or high-grade myopia
      is a leading cause of blindness because of its associated ocular morbidities of
      retinal detachment, macular choroidal degeneration, premature cataract, and
      glaucoma. Ample evidence documents the heritability of the non-syndromic forms of
      this condition, especially for high-grade myopia, commonly referred to as myopic
      spherical refractive power of 5 to 6 diopters or higher. Multiple high-grade
      myopia genetic loci have been identified, and confirmatory studies identifying
      high-grade and moderate myopia loci have also occurred. In general, myopia
      susceptibility genes are unknown with few association studies performed, and
      without confirmation in other research laboratories or testing of separate
      patient cohorts.

PMID- 19104472
TI  - The emperor's new clothes.

PMID- 19104473
TI  - What is the value of narrative research as a form of enquiry in palliative care
      nursing?

PMID- 19104474
TI  - Bereaved parents' experiences of the use of 'cold bedrooms' following the death
      of their child.
AB  - INTRODUCTION: Children's hospices have the facilities to enable a child to remain
      at the hospice following their death until the time of the funeral if desired by
      the family. The use of cold bedrooms (or beds) to reduce the rate of the body's
      physical deterioration enables the family to have unrestricted access and close
      proximity to the child throughout the 24-hour period. AIM: To explore how
      bereaved families experience the child remaining in a cold bedroom following the
      child's death in the period January 2002-March 2005. OBJECTIVE: To survey all the
      families whose child had been cared for in a cold bedroom in one children's
      hospice in South-East England (n=34). METHOD: A retrospective cross-sectional
      survey using a postal questionnaire was conducted. Questionnaires were sent to
      the 31 bereaved families who were considered eligible for participation.
      RESPONSE: Sixteen completed questionnaires were returned (51.6%); four families
      declined participation (12.9%); eleven families did not reply (35.5%). RESULTS:
      The experiences of sixteen families were obtained. The families expressed that
      they found the experience physically, practically and emotionally supportive, as
      they were able to continue to act as the child's parents, to choose and control
      how their child's care occurred, to say their farewells at their own pace and to
      plan the funeral of their choice. These results must be interpreted with the
      clear recognition that the experiences of 48.4% of the sample are unknown.
      Reasons for non-participation were explored. CONCLUSION: The study has
      methodological limitations but presents an investigation into the experiences of
      parents whose child has been cared for in a cold bedroom. These families all
      described the experience positively.

PMID- 19104475
TI  - Exploring nurses' attitudes to, and use of, an online palliative care resource.
AB  - AIM: The internet provides access to information and evidence that can support
      palliative care practice. This study aims to evaluate the use and utility of a
      palliative care website with particular regard to its use and issues for nurses.
      STUDY DETAILS: A survey of online visitors and a postal survey of staff working
      in palliative care services were conducted; 134 visitors completed the survey and
      371 staff in palliative services responded. FINDINGS: Users of the site found the
      content credible and over 95% would recommend the site to others. Over 90% of
      specialist palliative care nurses use online resources and half use the
      CareSearch website. Awareness of the resource was much lower for registered
      nurses than specialist nurses working in palliative care. CONCLUSION:
      Understanding attitudes to, and use of, online palliative care resources by
      nurses working in palliative care services could help to develop these resources
      to more effectively meet their needs and circumstances.

PMID- 19104476
TI  - Children affected by genetic conditions in end-of-life care. Part 1: Development
      of a study.
AB  - BACKGROUND: Many children receiving hospice care are affected by inherited
      genetic conditions. To provide appropriate care, children's hospice nurses
      require knowledge and awareness of the issues faced by the child and their family
      along with the implications of having, or being at risk from, an inherited
      genetic condition. Little is currently known about the competence levels of
      children's hospice nurses to support these children and their families. AIM: This
      study aims to explore how important children's hospice nurses perceived genetics
      to be within children's hospice care provision, and their level of confidence in
      meeting the care needs of children and their families with a genetic
      predisposition to disease. METHOD: This study involved two stages: a single-page
      survey to children's hospice directors of nursing designed to determine the
      nature of children's hospice care provision in England and Wales. Second, a
      postal survey using a structured, self-administered questionnaire was sent to
      nursing staff in a sample of children's hospices in England and Wales. A total of
      277 packs were sent to the hospices for distribution to children's nurses working
      in their employment. Likert scales were used to rate the importance of genetic
      activities relevant to children's hospices, and nurses' confidence in performing
      them. Demographic data were also collected. The results, the discussion of the
      findings and implications for practice will be discussed in part 2.

PMID- 19104477
TI  - Development and implementation of a palliative care link-nurse programme in care
      homes.
AB  - The End of Life Care Strategy (Department of Health, 2008) stresses the
      importance of education for all healthcare professionals in the delivery of care
      in any setting. According to the recent End of Life Care report from the National
      Audit Office (2008), few care home staff have sufficient training in providing
      end-of-life care, highlighting communication skills and pain management as two
      target areas for training. This article explores the development and
      implementation by a hospice education department of a palliative care link nurse
      programme in care homes with nursing as a means of providing aspects of the
      required training. Maintaining the motivation and commitment of the care home
      staff and managers is seen as vital in sustaining the programme, which has been
      running successfully for 4 years. It is important to differentiate between care
      homes with nursing (those that used to be called nursing homes) and care homes
      without nursing (those that used to be called residential homes). The terminology
      has changed to reflect the different client group. An evaluation of the programme
      was undertaken after 1 year and the key findings are discussed and future
      developments are highlighted.

PMID- 19104478
TI  - Affective learning in end-of-life care education: the experience of nurse
      educators and students.
AB  - Preparing future nurses to care for dying patients and their families represents
      a challenge for nursing education. Affective learning, essential to nurture a
      caring perspective in end-of-life care, can elicit strong emotional reactions in
      students, to which nurse educators must remain keenly sensitive. This article
      presents the experience of nurse educators and students with experiential and
      reflective activities addressing the affective domain of learning, within an
      intensive 4-week undergraduate course on end-of-life care, developed with a
      competency-based approach. It stressed the importance of strategic teaching for
      developing interpersonal competencies in end-of-life care, but revealed
      difficulties for both nurse educators and students in assessing outcomes derived
      from affective learning.

PMID- 19104479
TI  - A retrospective audit of non-malignant admissions to a regional hospice in 2003
      and 2006.
AB  - AIM: There is increasing pressure to provide palliative care to patients on the
      basis of need, not diagnosis. Additionally, there is a paucity of literature
      describing how the palliative care community is rising to this challenge.
      METHODS: This retrospective audit investigated the number of patients without
      cancer admitted to a regional hospice in Dundee, Scotland, in 2003 compared with
      2006 and whether these patients had different characteristics to patients with
      cancer. RESULTS: There was a significant rise in the number of patients admitted
      with non-malignant conditions; 6/328 patients were admitted during 2003 with non
      malignant conditions compared with 23/340 in 2006 (P=0.0037). There were no
      differences in age (P=0.5), length of stay (P=0.57), outcome of admission
      (P=0.59) or reason for admission (P=0.7) when those without cancer were compared
      with a contemporaneous group of 60 consecutive patients admitted with cancer.
      DISCUSSION: Local increases in non-malignant admissions mirror national figures.
      Underlying reasons for the local increase were unable to be studied in this
      retrospective audit and would require further study. More needs to be known about
      how patients, their carers and staff feel about hospice care for those with
      advanced non-malignant conditions and where, how and by whom palliative care for
      all should be provided.

PMID- 19104481
TI  - Chemical composition of essential oil and leaf anatomy of Salvia bertolonii Vis.
      and Salvia pratensis L. (Sect. Plethiosphace, Lamiaceae).
AB  - The taxonomical relationship between Salvia pratensis and S. bertolonii has been
      unclear for a long time. Salvia bertolonii has alternatively been considered a
      synonym, a subspecies, a problematic subspecies and a form of Salvia pratensis.
      However, both these two species are sometimes used in traditional medicine
      instead of sage (Salvia officinalis) or as an adulteration for the same drug. In
      order to confirm the status of S. bertolonii, together with the potential
      identification characteristics for differentiation from sage, both taxa were
      analyzed through the analysis of their essential oils, together with the
      micromorphological characteristics of the leaf surface and the anatomy and
      morphology of the leaves. The obtained results show that there are clear
      differences in the quantity of essential oil (0.073% for S. pratensis and 0.0016%
      for S. berolonii). The major compound in the essential oil of S. pratensis was E
      caryophyllene (26.4%) while in S. berolonii essential oil caryophyllene oxide was
      the major component (35.1%). The micromorphological differences are also
      pronounced in the leaf indumentum (density and distribution of certain types of
      non-glandular and glandular trichomes). Clear distinction between the
      investigated Salvia species is also observed in the leaf anatomy (in S. pratensis
      leaves are thinner, palisade tissue is made of 1-2 layers of cells, and leaves of
      S. bertolonii are characterized by 2-3 layers of palisade tissue cells, and
      consequently thicker).

PMID- 19104482
TI  - A new method for the determination of nucleic acid using an Eu3+- nicotinic acid
      complex as a resonance light scattering probe.
AB  - This study found that in Tris-HCl buffer, the resonance light scattering (RLS)
      intensity of the Eu(3+)-nicotinic acid system can be greatly enhanced by nucleic
      acids and the enhanced intensity is proportional to the concentration of nucleic
      acid in the range of 7 x 10(-8)-1 x 10(-5 ) g x mL(-1) for fsDNA, and its
      detection limit is 2 x 10(-8 ) g x mL(-1). Based on this, a new method for the
      determination of nucleic acids is proposed. Synthetic and actual samples are
      determined satisfactorily. The interaction mechanism is also studied. It is
      thought that nucleic acid can bind with the Eu(3+)-nicotinic acid complex through
      electrostatic attraction and thus form a large Eu(3+)-nicotinic acid-nucleic acid
      complex.

PMID- 19104484
TI  - Caffeic acid derivatives from Eupatorium perfoliatum L.
AB  - From the ethyl acetate soluble fraction of a methanol/water extract of the herb
      Eupatorium perfoliatum L. (Asteraceae) six caffeic acid derivatives have been
      isolated and identified by 1D- and 2D-NMR spectroscopic data. Besides the common
      quinic acid derivatives 5-caffeoylquinic acid (chlorogenic acid), 3
      caffeoylquinic acid (neochlorogenic acid) and 3,5-dicaffeoylquinic acid, three up
      to now unknown depsides of caffeic acid with glucaric acid have been isolated:
      2,5-dicaffeoylglucaric acid, 3,4-dicaffeoylglucaric acid, and 2,4- or 3,5
      dicaffeoylglucaric acid.

PMID- 19104483
TI  - Synthesis and evaluation of non-peptidic cysteine protease inhibitors of P.
      falciparum derived from etacrynic acid.
AB  - A series of etacrynic acid derivatives was synthesized and screened for their in
      vitro activity against Plasmodium falciparum, as well as their activity against
      recombinantly expressed falcipain-2 and -3. The two most active compounds of the
      series displayed IC(50) values of 9.0 and 18.8 microM against Plasmodia.

PMID- 19104485
TI  - Structure-activity relationship of flavonoids active against lard oil oxidation
      based on quantum chemical analysis.
AB  - In this study, the antioxidant activities of 15 flavonoids against lard oil
      oxidation were determined by using the Rancimat test. Quercetin,
      dihydromyricetin, luteolin and kaempferol showed the strongest antioxidant
      activity, with protection factor values (PF) of 11.50, 11.29, 4.24 and 2.49,
      respectively. The role of conjugated hydroxyl groups of the B and C ring is
      discussed. By using the following descriptors: DeltaH(f) (the difference in heat
      of formation between flavonoids and their free radicals resulted after hydrogen
      atom donation) and H(BC) (the number of conjugated hydroxyl groups of the B and C
      ring), the result obtained in the antioxidant Rancimat test could be successfully
      explained.

PMID- 19104486
TI  - Gastric and duodenal antiulcer activity of alkaloids: a review.
AB  - Peptic ulcer disease is a deep gastrointestinal erosion disorder that involves
      the entire mucosal thickness and can even penetrate the muscular mucosa. Numerous
      natural products have been evaluated as therapeutics for the treatment of a
      variety of diseases, including this one. These products usually derive from plant
      and animal sources that contain active constituents such as alkaloids,
      flavonoids, terpenoids, tannins and others. The alkaloids are natural nitrogen
      containing secondary metabolites mostly derived from amino acids and found in
      about 20% of plants. There has been considerable pharmacological research into
      the antiulcer activity of these compounds. In this work we review the literature
      on alkaloids with antiulcer activity, which covers about sixty-one alkaloids,
      fifty-five of which have activity against this disease when induced in animals.

PMID- 19104487
TI  - A preliminary pharmacokinetic study of betulin, the main pentacyclic triterpene
      from extract of outer bark of birch (Betulae alba cortex).
AB  - During the last two decades triterpenes have attracted attention because of their
      pharmacological potential. Triterpene extract (TE) from outer bark of birch
      consisting mainly of betulin is able to form an oleogel which was successfully
      tested in the treatment of actinic keratosis. Some aspects of TE in vitro
      pharmacology are already known. Now we show preliminary pharmacokinetics of
      betulin and results of a subchronic toxicity study of TE in rats and dogs.
      Because of poor aqueous solubility of the TE-triterpenes (< 0.1 microg/mL
      respectively), for pharmacokinetic studies it was suspended in sesame oil (rats,
      i.p.) and PEG 400 / 0.9 % NaCl (dogs, s.c.). I.p. administered, betulin, the main
      component of TE, shows time dependency over a period of 4 h and reaches a dose
      independent serum level of 0.13 microg/mL. Dose dependency was observed with s.c.
      administration. At 300 mg/kg a maximum plasma concentration of 0.33 microg/mL
      betulin was detected after 28 daily applications. The subchronic toxicity study
      showed no toxicity of TE in rats (i.p.) and dogs (s.c.). In conclusion,
      triterpene extract from birch bark is safe, its betulin is bioavailable and in
      addition to published triterpene biological activities TE provides high potential
      for further pharmaceutical and pharmacological research.

PMID- 19104488
TI  - Organocatalytic oxidative dehydrogenation of dihydroarenes by dioxygen using 2,3
      dichloro-5,6-dicyano-benzoquinone (DDQ) and NaNO2.
AB  - The oxidative dehydrogenation of dihydroarenes catalyzed by 2,3-dichloro-5,6
      dicyano-benzoquinone(DDQ) and NaNO(2) with dioxygen is reported. The combination
      of DDQ and NaNO(2) showed high efficiency and high selectivity, compared with
      other benzoquinones and anthraquinones, e.g., >99% conversion of 9,10
      dihydroanthracene with 99% selectivity for anthracene can be obtained at 120
      degrees C under 1.3 MPa O(2) for 8 h. Excellent results were achieved in the
      oxidative dehydrogenation of variety of dihydroarenes.

PMID- 19104489
TI  - Dodecatungstophosphoric acid (H3PW 12O40), samarium and ruthenium (III) chloride
      catalyzed synthesis of unsaturated 2-phenyl-5(4H)-oxazolone derivatives under
      solvent-free conditions.
AB  - We found that dodecatungstophosphoric acid (H(3)PW(12)O40), samarium and
      ruthenium(III) chloride act as efficient catalysts for synthesis of unsaturated 2
      phenyl-5(4H)oxazolone derivatives under solvent-free conditions. The key features
      of the reported protocols are short reaction times, high yields of products,
      ambient conditions and simple workup.

PMID- 19104490
TI  - Hematopoietic progenitor cell mobilization and harvesting in children with
      malignancies: do the advantages of pegfilgrastim really translate into clinical
      benefit?
AB  - Our purpose was to assess success rates in children of achieving optimal
      hematopoietic progenitor cells (HPCs) harvest after mobilization with 300
      microg/kg pegfilgrastim. Between January 2005 and January 2007, 26 children with
      solid malignancies who were referred for HPC collection were consecutively
      included. Hematopoietic progenitor cell mobilization consisted of one s.c.
      injection of 300 microg/kg body weight (BW) of pegfilgrastim. The success
      criterion was defined as at least 5 x 10(6) CD34+ cells/kg during the first
      standard apheresis (less than 3 blood volumes processed (BVP)). After 26
      inclusions, the Bayesian analysis gave a mean estimated success rate of 60.7%
      (95% credibility interval: 42.0-78.0%). The first apheresis allowed the
      collection of 8.3 x 10(6) CD34+ cells/kg BW (range 0.6-37.8), with a median of
      2.8 BVP (range 1.4-3.0). Overall, the median of CD34+ cells collected was 12.4 x
      10(6)/kg (range 2.7-37.8). The cumulative dose of anthracyclin was the only
      variable associated with the total number of CD34+ collected cells (P<0.05).
      Mobilization was clinically well tolerated in 20 patients. No drug-related
      adverse events of grade > or =3 occurred. We conclude that a single injection of
      300 microg/kg pegfilgrastim in the hematological steady state is an efficient and
      well-tolerated method of HPC mobilization in children with solid malignancies.

PMID- 19104491
TI  - Reversible dasatinib-induced pulmonary arterial hypertension and right ventricle
      failure in a previously allografted CML patient.

PMID- 19104492
TI  - Similar risks for hypothyroidism after allogeneic hematopoietic cell
      transplantation using TBI-based myeloablative and reduced-intensity conditioning
      regimens.
AB  - The risk of hypothyroidism after reduced-intensity hematopoietic cell
      transplantation (HCT) is not well known. We studied the incidence of
      hypothyroidism among a cohort of HCT recipients who had survived for > or =1 year
      and received a TBI-based myeloablative (MA) (N=84) or reduced-intensity (N=97)
      conditioning (RIC) regimen. MA HCT recipients were younger at the time of
      transplant (median age 37 vs 54 years, P<0.01), otherwise the two groups were
      comparable. Median follow-up was 28 (range, 12-75) months for MA and 25 (range,
      12-67) months for RIC group. The 3-year cumulative incidence of hypothyroidism
      was 8 and 5%, respectively (P=0.41). In multivariate analysis, both types of
      conditioning regimens were associated with similar risks for hypothyroidism
      (relative risk for MA 1.6 vs RIC). At least in the first few years after HCT, the
      risks for hypothyroidism are similar among patients receiving TBI-based MA and
      reduced-intensity regimens.

PMID- 19104493
TI  - Adaptation of family caregivers during the acute phase of adult BMT.
AB  - This study examined the course of adaptation as indicated by the level of
      emotional distress for family caregivers of adult BM recipients across the acute
      phase of the transplant trajectory. Factors influencing caregivers' adaptation
      that could be potential markers of vulnerability to psychological and social
      morbidity were identified. The sample included 192 caregivers of either an
      autologous or allogeneic BMT recipient. Data were collected by self-report
      questionnaires at three time points in the trajectory: pre-transplant/pre
      hospitalization (T1); during hospitalization, post-infusion (T2); 1 month post
      discharge (T3). There was a decline in emotional distress from T1 to T3, and
      bivariate correlations indicated significant association of distress with
      variables hypothesized to be theoretically relevant. Specifically, greater
      personal control, a greater sense of spiritual connectedness, less disruption in
      the life of the caregiver and less use of avoidance coping were the strongest
      factors associated with lower emotional distress. In conclusion (1) levels of
      personal control and spirituality remained stable across time and were negatively
      associated with emotional distress. Therefore, they may provide an indication of
      caregiver resilience pre-transplant; (2) level of recipient symptomatology rather
      than BMT type appears to influence caregiver distress; (3) there are indications
      of the need for post-hospitalization follow-up with caregivers by the BMT team.

PMID- 19104494
TI  - Perforation of the superior vena cava after subclavian catheterization: a rare
      complication after autologous PBSCT.

PMID- 19104495
TI  - Prior immunosuppressive therapy with antithymocyte globulin increases the risk of
      EBV-related lymphoproliferative disorder following allo-SCT for acquired aplastic
      anaemia.
AB  - We reviewed the incidence and risk factors for EBV-related post-transplant
      lymphoproliferative disorder (EBV-PTLD) in 89 patients with acquired aplastic
      anaemia (AAA) receiving allogeneic transplants between 1989 and 2006. The overall
      incidence of EBV-PTLD was 6.3% (5/89) with no cases in those receiving an
      allograft for constitutional BM failure syndromes (n=30) during the same period.
      There was no impact of age, gender, donor status, CMV seropositivity, GVHD and
      graft cell dose on the occurrence of PTLD. Although both reduced intensity
      conditioning (RIC) and the prior use of antithymocyte globulin (ATG), as
      immunosuppressive therapy (IST), were identified as the risk factors for PTLD,
      only prior use of ATG strongly influenced the development of PTLD with an
      incidence of 13.38+/-5.6% (5/43), compared with none in those not exposed to ATG
      before transplantation (P=0.01) with a relative risk of 10.39 for each course of
      prior ATG. This is the first study in patients with AAA documenting that those
      receiving multiple prior courses of ATG are at the highest risk of developing EBV
      PTLD.

PMID- 19104496
TI  - Hematopoietic SCT in patients with a history of invasive fungal infection.
AB  - Earlier invasive fungal infections (IFI) put recipients of hematopoietic SCT
      (HSCT) at a high risk of IFI-related mortality. We retrospectively assessed the
      feasibility of HSCT for patients with a history of IFI and the efficacy of
      secondary prophylaxis. From January 2001 to December 2007, 49 patients with a
      history of IFI underwent HSCT and most of them received broad-spectrum antifungal
      agents as secondary prophylaxis. After a median follow-up of 355 days (15-967),
      nine patients experienced failure of IFI prophylaxis, including three cases of
      IFI-related death, leading to a 2-year cumulative incidence of 18.4 and 6.1%,
      respectively. Four risk factors for the failure of prophylaxis were found, namely
      time interval from the diagnosis of IFI to transplantation, residual diseases
      before transplantation, infection with CMV and use of corticosteroid for the
      treatment of GVHD. A similar outcome can be achieved in recipients of Auto- and
      Auto-HSCT. Despite a higher risk of post-transplant progression, residual
      features of IFI did not affect the overall outcome of HSCT. In conclusion, a
      history of IFI and residual features are not contraindications to HSCT and
      secondary prophylaxis by broad-spectrum antifungal agents can protect patients
      from relapse or progression of an earlier infection.

PMID- 19104497
TI  - Early reconstitution of effector memory CD4+ CMV-specific T cells protects
      against CMV reactivation following allogeneic SCT.
AB  - Reactivation of CMV is a common complication following allogeneic haematopoietic
      SCT and is associated with significant morbidity and mortality. The relative
      importance of the CD4+ and CD8+ components of the CMV-specific immune response in
      protection from reactivation is unclear. The CMV-specific CD4+ and CD8+ immune
      response was measured at serial time points in 32 patients following allogeneic
      HSCT. Intracellular cytokine staining following CMV lysate stimulation and HLA
      peptide tetramers were used to determine CMV-specific CD4+ and CD8+ responses,
      respectively. A deficient CMV-specific CD4+ T-cell immune response within the
      first 30-50 days post transplant was associated with high risk of viral
      reactivation. Patients with combined impairment of the CD4+ and CD8+ immune
      response within the first 100 days were susceptible to late viral reactivation.
      The frequency of CMV-specific CD4+ T cells correlated with CMV-specific CD8+ T
      cells, comprising 10% of the whole T-cell repertoire. Early CMV-specific CD4+ T
      cell reconstitution was dominated by effector memory cells with normal levels of
      IL-2 resuming 6 months following transplantation. In summary, both CD4 and CD8
      CMV-specific immune reconstitution is required for protection from recurrent
      activation. Measurement of the magnitude of the CMV-specific CD4+ immune response
      is useful in managing viral reactivation following HSCT.

PMID- 19104498
TI  - Scaffold proteins and immune-cell signalling.
AB  - Over the past 20 years great progress has been made in defining most of the key
      signalling pathways that functionally regulate immune cells. Recently, it has
      become clear that scaffold proteins have a crucial role in regulating many of
      these signalling cascades. By binding two or more components of a signalling
      pathway, scaffold proteins can help to localize signalling molecules to a
      specific part of the cell or to enhance the efficacy of a signalling pathway.
      Scaffold proteins can also affect the thresholds and the dynamics of signalling
      reactions by coordinating positive and negative feedback signals. In this Review,
      we focus on recent progress in the understanding of the function of scaffold
      proteins in immune cells.

PMID- 19104499
TI  - The ageing immune system: is it ever too old to become young again?
AB  - Ageing is accompanied by a decline in the function of the immune system, which
      increases susceptibility to infections and can decrease the quality of life. The
      ability to rejuvenate the ageing immune system would therefore be beneficial for
      elderly individuals and would decrease health-care costs for society. But is the
      immune system ever too old to become young again? We review here the promise of
      various approaches to rejuvenate the function of the immune system in the rapidly
      growing ageing population.

PMID- 19104503
TI  - Mycobacterium tuberculosis infection of human monocyte-derived macrophages leads
      to apoptosis of T cells.
AB  - The induction of apoptosis of T cells by intracellular pathogen is an attractive
      hypothesis to explain their persistence in host cells. To test this hypothesis,
      human monocyte-derived macrophages were infected with Mycobacterium tuberculosis
      H37Rv and cocultured with autologous T cells stimulated with nonspecific
      phytohemagglutinin (PHA) or specific culture filtrate protein (CFP) of M.
      tuberculosis. CD95 (Fas) expression, propidium iodide (PI) staining and terminal
      deoxy nucleotidyl transferase (TdT)-mediated dUTP nick end labeling (TUNEL) assay
      of CD3 cells were studied to assess the viability. Apoptotic cells were
      correlated with the levels of nitric oxide (NO) and tumor necrosis factor-alpha
      (TNF-alpha). An increased CD3/PI and CD3/CD95(+) PHA-preactivated T cells in
      coculture with M. tuberculosis-infected macrophages suggested Fas-Fas ligand
      interactions to be important in apoptosis of nonspecifically stimulated T cells.
      Significantly higher NO and TNF- alpha levels suggested an association of the
      soluble factors with apoptosis of nonspecifically activated T cells.
      Significantly high release of TNF-alpha in the coculture of infected macrophages
      with CFP-activated T cells pointed toward its association with specific T-cell
      apoptosis. We show for the first time that in vitro infection of human
      macrophages with M. tuberculosis induces apoptosis of specific and to a much
      greater extent of nonspecific T cells.

PMID- 19104500
TI  - Annexin A1 and glucocorticoids as effectors of the resolution of inflammation.
AB  - Glucocorticoids are widely used for the management of inflammatory diseases.
      Their clinical application stems from our understanding of the inhibitory effect
      of the corticosteroid hormone cortisol on several components of the immune
      system. Endogenous and exogenous glucocorticoids mediate their multiple anti
      inflammatory effects through many effector molecules. In this Opinion article, we
      focus on the role of one such effector molecule, annexin A1, and summarize the
      recent studies that provide insight into its molecular and pharmacological
      functions in immune responses. In addition, we propose a model in which
      glucocorticoids regulate the expression and function of annexin A1 in opposing
      ways in innate and adaptive immune cells to mediate the resolution of
      inflammation.

PMID- 19104501
TI  - Prostate cancer genomics: towards a new understanding.
AB  - Recent genetics and genomics studies of prostate cancer have helped to clarify
      the genetic basis of this common but complex disease. Genome-wide studies have
      detected numerous variants associated with disease as well as common gene fusions
      and expression 'signatures' in prostate tumours. On the basis of these results,
      some advocate gene-based individualized screening for prostate cancer, although
      such testing might only be worthwhile to distinguish disease aggressiveness.
      Lessons learned from these studies provide strategies for further deciphering the
      genetic causes of prostate cancer and other diseases.

PMID- 19104504
TI  - Type II-activated macrophages suppress the development of experimental autoimmune
      encephalomyelitis.
AB  - Treatment with immune complexes, which ligate Fcgamma receptors (FcgammaRs),
      suppresses the development of experimental autoimmune encephalomyelitis (EAE). To
      determine the mechanism of action, we investigated how these immune complexes
      affected type II activation of macrophages (that is, exposure to immune complexes
      in a proinflammatory environment). Our results show that lower doses of
      interferon-gamma (IFN-gamma) were more effective at priming bone marrow-derived
      macrophages (BMMphi) to produce more interleukin 10 (IL-10) and less IL-12p40 in
      response to lipopolysaccharide (LPS) and immune complexes compared with LPS
      alone. Moreover, at the lowest level of IFN-gamma (20 U ml(-1)), a significant
      downregulation in the surface expression of CD40, CD80 and PD-L1 was observed in
      LPS and immune complex-stimulated macrophages (that is, type II activated) than
      macrophages stimulated with LPS alone (that is, classically activated). Finally,
      treatment of mice with type II-activated macrophages protected them from
      developing EAE, suggesting that administration of immune complexes is protective
      against EAE by inducing type II-activated macrophages.

PMID- 19104505
TI  - A new statistical screening approach for finding pharmacokinetics-related genes
      in genome-wide studies.
AB  - Biomedical researchers usually test the null hypothesis that there is no
      difference of the population mean of pharmacokinetics (PK) parameters between
      genotypes by the Kruskal-Wallis test. Although a monotone increasing pattern with
      a number of alleles is expected for PK-related genes, the Kruskal-Wallis test
      does not consider a monotonic response pattern. For detecting such patterns in
      clinical and toxicological trials, a maximum contrast method has been proposed.
      We show how that method can be used with pharmacogenomics data to a develop test
      of association. Further, using simulation studies, we compare the power of the
      modified maximum contrast method to those of the maximum contrast method and the
      Kruskal-Wallis test. On the basis of the results of those studies, we suggest
      rules of thumb for which statistics to use in a given situation. An application
      of all three methods to an actual genome-wide pharmacogenomics study illustrates
      the practical relevance of our discussion.

PMID- 19104507
TI  - Therapeutic effects of gelatin matrix-embedded IL-12 gene-modified macrophages in
      a mouse model of residual prostate cancer.
AB  - We evaluated the potential use of intraoperative gelatin matrix hemostatic
      sealant (GMHS; FloSeal; Baxter Healthcare) embedded with macrophages (Mphi)
      transduced with murine interleukin (IL)-12 recombinant adenoviral vector
      (G/Mphi/AdmIL-12) for prevention of recurrence of prostate cancer following
      radical prostatectomy. Application of G/Mphi/AdmIL-12 resulted in significant
      suppression of tumor growth and spontaneous lung metastases, a statistically
      significant survival advantage of the G/Mphi/AdmIL-12-treated animals, more
      efficient trafficking of Mphi to lymph nodes draining from the prostate and
      generation of systemic natural killer cell activity and tumor-specific cytolytic
      T lymphocyte responses compared to the controls in a preclinical mouse model of
      residual prostate cancer. Our data recommend this treatment as a novel adjuvant
      for prevention of local recurrence of prostate cancer following radical
      prostatectomy.

PMID- 19104506
TI  - Variations in the interleukin-1 receptor antagonist gene impact on survival of
      patients with advanced colorectal cancer.
AB  - The interleukin-1 receptor antagonist (IL-1RA) cytokine is thought to counteract
      tumor angiogenesis/metastasis. Two single nucleotide polymorphisms in the IL-1RA
      gene (rs4251961 T/C and rs579543 C/T) influence IL-1RA circulating levels with
      highest production in carriers of the homozygous rs4251961 T/T and rs579543 T/T
      genotypes. A total of 180 patients with metastatic colorectal cancer were
      categorized as high IL-1RA producers if they were carriers of at least one of the
      rs4251961 T/T or rs579543 T/T genotypes (T/T carriers). Median survival times
      were 35.8 months (95% confidence interval: 29.7-43.7 months) and 28.6 months (95%
      confidence interval: 25.6-30 months) in 56 T/T carriers and in 124 non-T/T
      carriers, respectively. The favorable association between T/T carriers' status
      and survival was significant in the multivariate analysis (P=0.018). Also, T/T
      carriers and non-T/T carriers were prevalent among patients with Karnofsky
      performance status 90-100 and 70-80, respectively (P=0.002). These findings
      encourage additional studies in this field and the evaluation of a recombinant-IL
      1RA for anticancer activity.

PMID- 19104508
TI  - The use of one-channel water cystometry in patients with a spinal cord lesion:
      practicalities, clinical value and limitations for the diagnosis of neurogenic
      bladder dysfunction.
AB  - STUDY DESIGN: Investigational technique evaluation. OBJECTIVE: To evaluate the
      clinical value and limitations of one-channel cystometry as a method for
      urodynamic testing in patients with spinal cord lesion (SCL). SETTING: Spinal
      Cord Injury Centers Asia. METHODS: Protocol, equipment and practical performance
      of the one-channel cystometry as used in Ho Chi Minh City and Chiang Mai were
      studied. RESULTS: One-channel cystometry permits to accurately evaluate bladder
      pressure development at constant filling speed. It shows detrusor muscle
      behaviour as detrusor overactivity and allows evaluating sensation of bladder
      filling. It can strongly suggest detrusor external sphincter dyssynergia. The
      need of bladder-relaxant drugs and their effectiveness can be evaluated. The
      major limitation is that the one pressure line will show changes of intravesical
      pressure independent of their cause, which makes a continuous thorough
      observation mandatory throughout the test. Other limitations are a filling rate
      higher than physiological and a filling solution at room temperature. As in more
      elaborate urodynamic testing, the observations do therefore not necessarily
      reflect the function of the lower urinary tract in daily life. CONCLUSION: One
      channel cystometry is easy to perform, cheap and clinically valid. The results
      need to be integrated in the overall knowledge of the patient's neurological
      situation. The method permits one to gather a lot of information on bladder
      function in persons with SCL. With proper interpretation and a clear
      understanding of the shortcomings, it is a good guide for bladder management. It
      is applicable everywhere.

PMID- 19104509
TI  - NMO-IgG-negative relapsing myelitis.
AB  - OBJECTIVE: Idiopathic transverse myelitis (I-TM) is typically monophasic, while
      relapsing forms are usually referred to spinal cord-restricted neuromyelitis
      optica (NMO), atypical multiple sclerosis (MS), or myelitis during the course of
      infections and connectivitis. Our objective was to evaluate the frequency of
      recurrent I-TM; to clarify the nosology of these forms through comparison with
      NMO and post-infectious TM (P-TM). DESIGN: Prospective cohort study on patients
      presenting with I-TM was carried out inpatients of Infectious and Neurologic
      Disease Clinics, Italy. METHODS: Over an 8-year period, we recruited 13 patients
      with I-TM and 16 with P-TM. The patients were followed-up for at least 3 years
      with repeated brain and spinal cord magnetic resonance imaging (MRI)
      examinations, multimodal evoked potentials and serum screen for connectivitis.
      Relapses were defined on clinical and imaging criteria. RESULTS: Four patients
      with I-TM (31%) had a relapsing course . They were all males with age >50, and
      severe at-onset disability. The final outcome was poor in three out of four
      patients. Serum NMO-immunoglobulin G was undetectable in all patients.
      Longitudinally extensive myelitis was not predictive of relapses. I-TM and P-TM
      shared clinical, cerebrospinal fluid (CSF) and MRI features, as well as a similar
      rate (54 vs 38%) of peripheral nervous system involvement (polyradiculoneuritis),
      and an identical rate of relapses (31% for both forms). CONCLUSIONS: Our series
      support the existence of relapsing I-TM as a disease entity that does not appear
      related to NMO, nor to MS, cannot be further specified and shares many features
      with P-TM. The likelihood of relapses was unpredictable based on clinical, CSF
      and MRI findings.

PMID- 19104510
TI  - Activities of daily living performed by individuals with SCI: relationships with
      physical fitness and leisure time physical activity.
AB  - STUDY DESIGN: Cross-sectional. OBJECTIVES: To examine patterns of participation
      in activities of daily living (ADL) and fitness-related factors associated with
      these patterns among individuals with spinal cord injury (SCI). SETTING: Centre
      for Health Promotion and Rehabilitation at McMaster University, School of
      Kinesiology and Health Studies at Queen's University. METHODS: Forty-eight
      participants completed the Physical Activity Recall Assessment for People with
      Spinal Cord Injury (PARA-SCI) and a fitness test assessing cardiovascular fitness
      (VO(2max) and peak power output (Po)). The most commonly reported ADL were
      extracted from the PARA-SCI data for analysis. RESULTS: Women tended to spend
      more time participating in domestic and personal care ADL than men. Compared to
      individuals with tetraplegia, individuals with paraplegia tended to spend more
      time transferring, cleaning and preparing food and less time wheeling, toileting
      and dressing. Fitness and participation in leisure time physical activity (LTPA)
      were associated with certain ADL. Participants with higher levels of fitness
      spent more time partaking in ADL wheeling and cleaning. Moreover, greater time
      spent participating in moderate- and heavy-intensity LTPA was positively
      correlated with time spent engaged in certain ADL. CONCLUSION: By identifying
      common ADL performed by individuals with SCI, the study findings begin to provide
      direction for developing strategies to optimize ADL participation. Future
      research should examine fitness as a way to help individuals with SCI optimize
      their ADL participation.

PMID- 19104511
TI  - Expression of purinergic P2X2-receptors in neurogenic bladder dysfunction due to
      spinal cord injury: a preliminary immunohistochemical study.
AB  - STUDY DESIGN: Retrospective descriptive study. OBJECTIVE: Although muscarinic
      receptors are the main targets for the treatment of detrusor overactivity today,
      anticholinergic therapy is not satisfying in a substantial percentage of
      patients. Recently, overexpression of P(2)X(2) receptors in patients with
      idiopathic overactive bladder was demonstrated, indicating that purinergic
      innervation may play an important role in the pathophysiology of detrusor
      overactivity. We evaluated the expression of P(2)X(2) receptors in patients with
      spinal cord lesions. SETTING: German university hospital. METHODS: By
      immunohistochemical staining, the frequency and intensity of P(2)X(2) expression
      in bladder specimens from 15 patients with suprasacral spinal cord lesion were
      compared to those from 11 patients with bladder disorders not related to spinal
      cord injury (overactive bladder: n=6; chronic non-obstructive retention: n=2;
      bladder tumour: n=3). RESULTS: Specimens (12/15) from patients with spinal cord
      lesions and specimens (8/11) without spinal cord lesions demonstrated staining
      for P(2)X(2) receptors in the detrusor muscle and the urothelium. There was a
      tendency towards a stronger staining in specimens from patients with spinal cord
      lesion. CONCLUSION: Our pilot study gives a first hint that the P(2)X(2)
      expression in patients with suprasacral spinal cord injury seems to be comparable
      to the expression in patients with idiopathic overactive bladder. Therefore,
      P(2)X(2) receptors in detrusor tissue may be a future target for the treatment of
      detrusor overactivity.

PMID- 19104512
TI  - ASIA impairment scale conversion in traumatic SCI: is it related with the ability
      to walk? A descriptive comparison with functional ambulation outcome measures in
      273 patients.
AB  - STUDY DESIGN: Prospective multicenter longitudinal cohort study. OBJECTIVES: To
      determine the relationship between improvements of the American Spinal Injury
      Association/International Spinal Cord Society (ASIA/ISCoS) neurological standard
      scale (AIS) outcome measure and improvements of functional ambulatory outcome
      measures in patients with traumatic spinal cord injury (SCI). SETTING: European
      multicenter study of human SCI (EM-SCI). METHODS: In 273 eligible patients with
      traumatic SCI, acute (0-15 days) and chronic phase (6 or 12 months) AIS grades,
      timed up and go (TUG) test and 10-m walk test (10MWT) outcome measurements were
      analyzed. Subanalysis of those patients who did have AIS conversion was performed
      to assess its relation with functional ambulatory outcomes. RESULTS: Studied
      population consisted of 161 acute phase AIS grade A patients; 37 grade B; 43
      grade C and 32 acute phase AIS grade D patients. Forty-two patients (26%)
      converted from AIS grade A, 27 (73%) from grade B, 32 (75%) from grade C and five
      patients (16%) from AIS grade D. The frequencies of AIS conversions and
      functional ambulation recovery outcomes were significantly different (P<0.001) in
      patients with motor complete SCI. The ratio of patients with both recovery of
      ambulatory function and AIS conversion (n=101) differed significantly (P<0.001)
      between the acute phase AIS grade scores; AIS grade A (6/40 patients, 15%), B
      (9/27 patients, 33%), C (23/29 patients, 79%) and D (5/5 patients 100%).
      CONCLUSIONS: The AIS conversion outcome measure is poorly related to the ability
      to walk in traumatic SCI patients. Therefore, the authors recommend the use of
      functional ambulation recovery outcome measures in prognosticating the recovery
      of walking capacity and performance of patients with SCI.

PMID- 19104513
TI  - Long-term outcome and safety of transanal colonic irrigation for neurogenic bowel
      dysfunction.
AB  - STUDY DESIGN: Long-term follow-up study. OBJECTIVES: Short-term results find
      transanal colonic irrigation (TAI) favourable in the treatment of neurogenic
      bowel dysfunction (NBD). Therefore, long-term results need to be described.
      SETTING: Department of Surgery P, Aarhus University Hospital, Denmark. METHODS:
      Between 1994 and 2007, 211 (115 female) patients with NBD (age: 7-81 years
      (median 49)) were introduced to TAI. One hundred and seventy-three patients had
      spinal cord injury and 38 had other neurological disorders. Data were obtained
      from hospital records and a mailed questionnaire. Treatment was considered
      successful in patients still using TAI, patients who had used TAI until they died
      and patients whose symptoms had resolved while using TAI. RESULTS: Successful
      outcome was achieved in 98 (46%) patients after a mean follow-up of 19 months
      (range 1-114 months). A Kaplan-Meier plot showed a dropout of 20% in the first 3
      months. After 3 years, the rate of success was 35% and remained almost unchanged
      afterwards. A regression analysis showed male gender (odds ratio (OR) 2.1), mixed
      symptoms (OR 2.9) and prolonged colorectal transit time (OR 2.4) to be
      significantly associated with successful outcome. One non-lethal bowel
      perforation occurred in approximately 50,000 irrigations (0.002%), whereas minor
      side effects were observed in 48%. CONCLUSION: After a mean follow-up of 19
      months, 46% was successfully treated. The rate of success was 35% after 3 years
      and remained almost unchanged afterwards. TAI is safe and can be introduced to
      most patients suffering from NBD.

PMID- 19104514
TI  - Targeting cancer with small molecule kinase inhibitors.
AB  - Deregulation of kinase activity has emerged as a major mechanism by which cancer
      cells evade normal physiological constraints on growth and survival. To date, 11
      kinase inhibitors have received US Food and Drug Administration approval as
      cancer treatments, and there are considerable efforts to develop selective small
      molecule inhibitors for a host of other kinases that are implicated in cancer and
      other diseases. Herein we discuss the current challenges in the field, such as
      designing selective inhibitors and developing strategies to overcome resistance
      mutations. This Review provides a broad overview of some of the approaches
      currently used to discover and characterize new kinase inhibitors.

PMID- 19104516
TI  - The need to test the theories behind the Polypill: rationale behind the Indian
      Polycap Study.

PMID- 19104515
TI  - Targeted and armed oncolytic poxviruses: a novel multi-mechanistic therapeutic
      class for cancer.
AB  - Viruses have been engineered for cancer therapy in a variety of ways. Approaches
      include non-replicating gene therapy vectors, cancer vaccines and oncolytic
      viruses, but the clinical efficacy of these approaches has been limited by
      multiple factors. However, a new therapeutic class of oncolytic poxviruses has
      recently been developed that combines targeted and armed approaches for treating
      cancer. Initial preclinical and clinical results show that products from this
      therapeutic class can systemically target cancers in a highly selective and
      potent fashion using a multi-pronged mechanism of action.

PMID- 19104518
TI  - Issues to consider in the pharmaceutical development of a cardiovascular
      polypill.
AB  - The pharmaceutical development of a cardiovascular polypill presents several
      unique challenges. The selection of the type and number of active drugs to be
      incorporated requires important consideration of clinical, pharmaceutical and
      commercial issues, and the final decision with regard to the polypill's
      components depends on how these issues are prioritized. Once the drug combination
      has been chosen, developers must determine which pharmaceutical formulation
      should be used. The most appropriate method of drug delivery can vary markedly
      and depends on the characteristics of the drugs to be combined. Finally, careful
      consideration of how to gather the type of information required by regulatory
      agencies before a particular polypill can be approved for use in the general
      population is crucial. Although the association of multiple, active ingredients
      in a single dosage form would represent a major step forward in the prevention of
      cardiovascular conditions, a careful evaluation of all the above-mentioned
      variables and a well thought-out development plan is mandatory to maximize the
      chances of success.

PMID- 19104520
TI  - Unconditionally stable indole-derived glass blends having very high
      photorefractive gain: the role of intermolecular interactions.
AB  - The photorefractivity of an indole derivative and of its polymer blends has been
      studied at room temperature. The indole derivative 3-[2-(4-nitrophenyl)ethenyl]-1
      (2-ethylhexyl)-2-methylindole (NPEMI-E) is a typical low-molecular-weight glass
      forming molecule having peculiar nonlinear optics characteristics. It is
      unconditionally soluble in the photoconductive poly-(N-vinyl-2,3-dimethylindole)
      so that all the possible blends can be studied for a weight percent (wt. %)
      content of NPEMI-E ranging from zero to 100. A very high and sharp maximum of the
      photorefractive optical gain Gamma(2) approximately 2000 cm(-1) was obtained for
      a NPEMI-E wt. % content of about 90. On the basis of recently published
      theoretical calculations, we have made the hypothesis that the rapid change of
      Gamma(2) can also be ascribed to a correspondingly quick variation of the
      molecular electro-optic parameters of the dissolved chromophore for some well
      distinguished values of its concentration in the polymer matrix. Differential
      scanning calorimetry measurements were made and the results carefully analyzed
      with the aim of obtaining information on the intermolecular interactions. These
      last measurements also allowed rationalizing the unconditionally stable glass
      appearance of the obtained blends. Measurements of spectroscopic ellipsometry
      were also made on blends with different NPEMI-E content.

PMID- 19104517
TI  - Cardiac manifestations of HIV infection: an African perspective.
AB  - The pericardium, myocardium, coronary arteries and pulmonary arteries are the
      main targets for cardiac disease in people who are infected with HIV. Geography
      and access to highly active anti-retroviral therapy (HAART) have a major
      influence on which of these targets is affected. In sub-Saharan Africa, where
      tuberculosis is endemic and access to HAART is limited, the dominant forms of HIV
      associated heart disease are pericardial tuberculosis and cardiomyopathy.
      However, in industrialized countries, where tuberculosis is rare and HAART is
      widely available, coronary artery disease is the main cause of death and
      disability in these patients. Observational data suggest that HAART, by
      preserving immune function, reduces the incidence of myopericardial disease and
      pulmonary hypertension. The result has been that, although optimal strategies to
      reduce vascular disease in this population continue to be sought and debated in
      industrialized nations, the focus of prevention and treatment strategies for HIV
      related heart disease in developing countries has been to support the active
      campaigns to get universal access to HAART in the first place. Herein, we review
      the cardiac manifestations of HIV in sub-Saharan Africa.

PMID- 19104521
TI  - Improving optical bench radius measurements using stage error motion data.
AB  - We describe the application of a vector-based radius approach to optical bench
      radius measurements in the presence of imperfect stage motions. In this approach,
      the radius is defined using a vector equation and homogeneous transformation
      matrix formulism. This is in contrast to the typical technique, where the
      displacement between the confocal and cat's eye null positions alone is used to
      determine the test optic radius. An important aspect of the vector-based radius
      definition is the intrinsic correction for measurement biases, such as
      straightness errors in the stage motion and cosine misalignment between the stage
      and displacement gauge axis, which lead to an artificially small radius value if
      the traditional approach is employed. Measurement techniques and results are
      provided for the stage error motions, which are then combined with the setup
      geometry through the analysis to determine the radius of curvature for a
      spherical artifact. Comparisons are shown between the new vector-based radius
      calculation, traditional radius computation, and a low uncertainty mechanical
      measurement. Additionally, the measurement uncertainty for the vector-based
      approach is determined using Monte Carlo simulation and compared to experimental
      results.

PMID- 19104519
TI  - Fixed-dose combination therapy and secondary cardiovascular prevention:
      rationale, selection of drugs and target population.
AB  - Ischemic heart disease and stroke are the leading causes of death worldwide. A
      large proportion of individuals at high 10-year risk of a cardiovascular event
      live in low-income and middle-income countries, and the large majority of all
      cardiovascular events occur in developing countries. A large amount of evidence
      supports the use of pharmacological treatment for the prevention of
      cardiovascular death in this population, including antiplatelet drugs, beta
      blockers, lipid-lowering agents and angiotensin-converting-enzyme inhibitors.
      However, the efficacy of cardiovascular prevention is hampered by several
      problems, including inadequate prescription of medication, poor adherence to
      treatment, limited availability of medications and unaffordable cost of
      treatment. Here we examine the use of fixed-dose combination therapy (a
      'polypill'), and how this therapy could improve adherence to treatment, reduce
      the cost and improve treatment affordability in low-income countries.

PMID- 19104522
TI  - Gaussian beam scattering by two parallel nonabsorbing dielectric cylinders:
      displacement and rotational degrees of freedom.
AB  - An extension of the problem of a moderately focused Gaussian beam scattered by an
      arrangement of two parallel nonabsorbing dielectric cylinders of arbitrary
      refraction indexes and radii is developed. The feature introduced in the present
      solution is the relative angular position coordinate between the two cylinders
      (phi(0)) as a degree of freedom. Explicit dependence on this variable of
      scattering coefficients, beam shape coefficient, and extinction efficiency is
      given. Together with the displacement coordinate d, various other scattering
      configurations can be studied. The applicability of the solution is given in the
      form of extinction curves taking phi(0) as the main parameter for variation. The
      model is proposed as a means of investigating evanescent wave microscopy.

PMID- 19104523
TI  - Spectral prediction model for color prints on paper with fluorescent additives.
AB  - I propose a model for predicting the total reflectance of color halftones printed
      on paper incorporating fluorescent brighteners. The total reflectance is modeled
      as the additive superposition of the relative fluorescent emission and the pure
      reflectance of the color print. The fluorescent emission prediction model
      accounts for both the attenuation of light by the halftone within the excitation
      wavelength range and for the attenuation of the fluorescent emission by the same
      halftone within the emission wavelength range. The model's calibration relies on
      reflectance measurements of the optically brightened paper and of the solid
      colorant patches with two illuminants, one including and one excluding the UV
      components. The part of the model predicting the pure reflectance relies on an
      ink-spreading extended Clapper-Yule model. On uniformly distributed surface
      coverages of cyan, magenta, and yellow halftone patches, the proposed model
      predicts the relative fluorescent emission with a high accuracy (mean
      DeltaE(94)=0.42 under a D65 standard illuminant). For optically brightened paper
      exhibiting a moderate fluorescence, the total reflectance prediction improves the
      spectral reflectance prediction mainly for highlight color halftones, comprising
      a proportion of paper white above 12%. Applications include the creation of
      improved printer characterization tables for color management purposes and the
      prediction of color gamuts for new combinations of optically brightened papers
      and inks.

PMID- 19104524
TI  - Near-infrared digital photography to estimate snow correlation length for
      microwave emission modeling.
AB  - The study is based on experimental work conducted in alpine snow. We made
      microwave radiometric and near-infrared reflectance measurements of snow slabs
      under different experimental conditions. We used an empirical relation to link
      near-infrared reflectance of snow to the specific surface area (SSA), and
      converted the SSA into the correlation length. From the measurements of snow
      radiances at 21 and 35 GHz, we derived the microwave scattering coefficient by
      inverting two coupled radiative transfer models (the sandwich and six-flux
      model). The correlation lengths found are in the same range as those determined
      in the literature using cold laboratory work. The technique shows great potential
      in the determination of the snow correlation length under field conditions.

PMID- 19104525
TI  - Airborne high spectral resolution lidar for profiling aerosol optical properties.
AB  - A compact, highly robust airborne High Spectral Resolution Lidar (HSRL) that
      provides measurements of aerosol backscatter and extinction coefficients and
      aerosol depolarization at two wavelengths has been developed, tested, and
      deployed on nine field experiments (over 650 flight hours). A unique and
      advantageous design element of the HSRL system is the ability to radiometrically
      calibrate the instrument internally, eliminating any reliance on vicarious
      calibration from atmospheric targets for which aerosol loading must be estimated.
      This paper discusses the design of the airborne HSRL, the internal calibration
      and accuracy of the instrument, data products produced, and observations and
      calibration data from the first two field missions: the Joint Intercontinental
      Chemical Transport Experiment--Phase B (INTEX-B)/Megacity Aerosol Experiment-
      Mexico City (MAX-Mex)/Megacities Impacts on Regional and Global Environment
      (MILAGRO) field mission (hereafter MILAGRO) and the Gulf of Mexico Atmospheric
      Composition and Climate Study/Texas Air Quality Study II (hereafter
      GoMACCS/TexAQS II).

PMID- 19104526
TI  - Design, calibration, and characterization of a field radiometer using light
      emitting diodes as detectors.
AB  - The Remote Sensing Group at the University of Arizona has developed multispectral
      ground-viewing radiometers that use light-emitting diodes as detectors. This work
      describes the optical design, electrical design, and laboratory calibration of a
      three-channel radiometer that operates in the visible and near-infrared region of
      the spectrum. The optical and electrical design of the radiometer is introduced,
      and then the calibration and characterization of the radiometer are described.
      Laboratory measurements include the spectral responsivity for each channel of the
      radiometer, the temperature dependence of the total responsivity for each
      channel, system linearity, field of view, and finally, the absolute radiometric
      calibration. A solar-radiation-based calibration is used to determine the
      absolute responsivity.

PMID- 19104527
TI  - Measured surface loss from luminescent solar concentrator waveguides.
AB  - The surface and edge emissions from dye-filled and dye-topped polycarbonate and
      polymethyl methacrylate luminescent solar concentrators were measured. We
      demonstrate that about 40-50% of the absorbed light energy (and 50-70% of the
      photons) is lost through the top and bottom surfaces of the filled waveguide. In
      most cases the escape cone losses are greater at the top than the bottom surface.

PMID- 19104528
TI  - Optimal parameters for retinal illumination and imaging in fundus cameras.
AB  - A fundus camera is a complex optical system for imaging the retina of the eye.
      Designing a fundus camera requires the combination of an imaging system and an
      illumination system to share common optics. This combination of systems results
      in the need to find an optimal balance between imaging and illuminating the
      retina. We present a series of parameters and methods used to optimize the
      illumination system of a fundus camera while maintaining excellent image quality.

PMID- 19104529
TI  - Asymmetrical optical lenslet array realized by spatial light modulator for
      measuring toroidal surfaces.
AB  - The Shack-Hartmann wavefront sensor (SHWS) recently has been extensively
      researched for optical surface metrology due to its extendable dynamic range
      compared with interferometry technique. In this paper, we proposed to use a
      digital SHWS to measure toroidal surfaces, which are widely used in many optical
      systems due to their different symmetries and curvatures in the X and Y
      directions. For what is believed to be the first time, an asymmetrical optical
      lenslet array implemented by a spatial light modulator was presented to tackle
      the measurement challenge. This unconventional design approach has a great
      advantage to provide different optical powers in the X and Y directions so that
      focusing spots can be formed and captured on the detector plane for accurate
      centroid finding and precise wavefront evaluation for 3D shape reconstruction of
      the toroidal surface. A digital SHWS system with this extraordinary microlens
      array was built to verify the design concept, and the experimental results were
      presented and analyzed.

PMID- 19104530
TI  - Low-complexity pixel detection for images with misalignment and interpixel
      interference in holographic data storage.
AB  - This paper presents an efficient solution to recovering data pixels of images
      that have undergone optical and electrical channel impairments in holographic
      data storage systems. The channel impairments considered include interpixel
      interference, three types of misalignment, and noise. The proposed misalignment
      compensation scheme, consisting of realignment and rate conversion, can
      effectively eliminate misalignment with more than 84% reduction in additions and
      74% reduction in multiplications. In addition, several low-complexity techniques
      are introduced to reduce the complexity of a two-dimensional maximum a posteriori
      pixel detection method by up to 95% and do so with negligible degradation in
      detection performance.

PMID- 19104531
TI  - Cross calibration of ocean-color bands from moderate resolution imaging
      spectroradiometer on Terra platform.
AB  - Ocean-color applications require maximum uncertainties in blue-wavelength water
      leaving radiances in oligotrophic ocean of approximately 5%. Water-leaving
      radiances from Moderate Resolution Imaging Spectroradiometer (MODIS) on the Terra
      satellite, however, exhibit temporal drift of the order of 15% as well as sensor
      changes in response versus scan and polarization sensitivity, which cannot be
      tracked by onboard calibrators. This paper introduces an instrument
      characterization approach that uses Earth-view data as a calibration source. The
      approach models the top of the atmosphere signal over ocean that the instrument
      is expected to measure, including its polarization, with water-leaving radiances
      coming from another well-calibrated global sensor. The cross calibration allows
      for significant improvement in derived MODIS-Terra ocean-color products, with
      largest changes in the blue wavelengths.

PMID- 19104532
TI  - Proposal of a Pr3+-doped telluride fiber amplifier for 1.3, 1.49, and 1.6 microm
      transmission windows.
AB  - A numerical model of a Pr(3+)-doped low-phonon-energy fiber pumped with 488, 980,
      and 1480 nm lasers is presented to explore the possibility for simultaneous 1300,
      1490, and 1600 nm band amplification for the first time, to the best of my
      knowledge. The rate and power propagation equations of the model are solved
      numerically and the dependence of the gains at the three bands on pump power and
      input signal power are calculated. The results predict that, with 488, 980, and
      1480 nm pump power of 100, 12, and 1.5 mW, and with Pr(3+) concentrations of
      1.2x10(25) ions/m(3), the signals around 1300, 1490, and 1600 nm can be equally
      amplified with a gain of 21.0 x dB in the active fiber with a length of 6.0 m.

PMID- 19104533
TI  - Reconstruction of the aerosol optical parameters from the data of sensing with a
      multifrequency Raman lidar.
AB  - A method of interpreting data of multifrequency Raman lidar sensing is developed.
      An algorithm for separating aerosol layers with different scattering properties
      and subsequently estimating the average value of the lidar ratio and Angstrom
      parameter within individual layers is suggested. The algorithm allows the error
      of reconstructing the backscattering coefficient from daytime observations to be
      at least halved. A well-posed numerical differentiation algorithm for determining
      the extinction coefficient is suggested for the interpretation of nighttime
      measurements based on the transformation of the range of allowable values that
      requires a solution of nonlinear equations. An iterative procedure envisaged for
      linearization improves the spatial resolution compared with the conventional
      methods. The methods can be successfully used to process routine lidar
      measurements under conditions of a priori uncertainty.

PMID- 19104534
TI  - Interferometric testbed for nanometer level stabilization of environmental motion
      over long time scales.
AB  - We developed an interferometric testbed to stabilize environmental motions over
      time scales of several hours and a length scale of 1 m. Typically, thermal and
      seismic motions on the ground are larger than 1 microm over these scales,
      affecting the precision of more sensitive measurements. To suppress such motions,
      we built an active stabilization system composed of interferometric sensors, a
      hexapod actuator, and a frequency-stabilized laser. With this stabilized testbed,
      environmental motions were suppressed down to the nanometer level. This system
      will allow us to perform sensitive measurements, such as ground testing of the
      Laser Interferometer Space Antenna, in the presence of environmental noise.

PMID- 19104535
TI  - Gaussian profile estimation in two dimensions.
AB  - We extend recent results for estimating the parameters of a one-dimensional
      Gaussian profile to two-dimensional profiles, deriving the exact covariance
      matrix of the estimated parameters. While the exact form is easy to compute, we
      provide a set of close approximations that allow the covariance to take on a
      simple analytic form. This not only provides new insight into the behavior of the
      estimation parameters, but also lays a foundation for clarifying previously
      published work. We also show how to calculate the parameter variances for the
      case of truncated sampling, where the profile lies near the edge of the array
      detector. Finally, we calculate expressions for the bias in the classical
      formulation of the problem and provide an approach for its removal. This allows
      us to show how the bias affects the problem of choosing an optimal pixel size for
      minimizing parameter variances.

PMID- 19104536
TI  - Laser-jamming effectiveness analysis of combined-fiber lasers for airborne
      defense systems.
AB  - The laser-jamming effectiveness of combined fiber lasers for airborne defense
      systems is analyzed in detail. Our preliminary experimental results are proof of
      the concept of getting a high-power laser through a beam combination technique.
      Based on combined fiber lasers, the jamming effectiveness of four-quadrant
      guidance and imaging guidance systems are evaluated. The simulation results have
      proved that for a four-quadrant guidance system, the tracking system takes only
      two seconds to complete tracking, and the new tracking target is the jamming
      laser; for the imaging guidance system, increasing the power of the jamming laser
      or the distance between the target and the jamming laser are both efficient ways
      to achieve a successful laser jamming.

PMID- 19104537
TI  - Excess noise reduction by optical technique in amplitude-sensitive heterodyne
      interferometer for small differential phase detection.
AB  - An amplitude-sensitive technique associated with a heterodyne interferometer for
      detecting small differential phase is reported. The excess noise with the
      amplitude-sensitive technique is reduced by optical subtraction instead of
      electronic subtraction. The differential phase introduced by the orthogonally
      polarized laser beams is converted to the amplitudes of two heterodyne
      interferometric signals, which presents amplitude and phase quadrature
      simultaneously. Thus the excess noise power and quantum noise power are both
      differential phase dependent. The advantages of differential and additive
      operations by optical technique and the real time differential phase
      determination without phase lock in are demonstrated experimentally. The
      theoretical signal-to-noise ratio (SNR) and minimum detectable differential phase
      are derived, which takes quantum noise and excess noise into consideration. The
      experimental results demonstrated the resolutions of differential phase detection
      closes to 10(-6) rad/square root(Hz) (10(-13) m/square root(Hz)) level over 100
      kHz bandwidth and at 10(-8) rad/square root(Hz) (10(-15) m/square root(Hz)) level
      over 125 MHz bandwidth, respectively, under 2.5 mW incident power.

PMID- 19104538
TI  - Water-scattered signal to compensate for the rough sea surface effect on bottom
      lidar imaging.
AB  - We investigate the possibility of using the water-backscattered radiation from a
      bottom sounding airborne imaging light detection and ranging (lidar) system to
      determine the surface slope at the point where the laser beam intersects the
      surface. We show that the refraction angle of the beam can be determined using
      receivers whose sensitivities vary linearly over their field of view. Equations
      are derived to estimate the statistical mean and variance values of this
      refracted angle. We demonstrate that the proposed algorithm improves lidar
      imaging. Numerical examples with reference to typical marine conditions are
      given.

PMID- 19104542
TI  - Synthetic quadrature phase detector/demodulator for Fourier transform
      spectrometers.
AB  - A method is developed to demodulate (velocity correct) Fourier transform
      spectrometer data that are taken with an analog to digital converter that
      digitizes equally spaced in time. This method makes it possible to use simple low
      cost, high-resolution audio digitizers to record high-quality data without the
      need for an event timer or quadrature laser hardware and makes it possible to use
      a metrology laser of any wavelength. The reduced parts count and simple
      implementation make it an attractive alternative in space-based applications when
      compared to previous methods such as the Brault algorithm.

PMID- 19104541
TI  - Passive quasi-monochromatic depth discrimination using a coherence imager with
      volume holographic pupil.
AB  - We present a new passive depth detection method for quasi-monochromatic and
      spatially incoherent objects. We utilize the wavefront discrimination properties
      of a volume holographic pupil combined with a measurement of the degree of
      coherence of the diffracted field. Depth detection is posed as the Bayesian
      hypothesis testing on the outcome of the coherence measurement. We present the
      analysis of our proposed optical system and experimental results confirming
      binary depth discrimination with high confidence for featureless objects.

PMID- 19104543
TI  - Extending the depth of field through unbalanced optical path difference.
AB  - We describe a simple method to extend the depth of field of a conventional camera
      by inserting a transparent annular ring in front of the pupil of the lens. The
      insertion of the ring creates an unbalanced optical path difference across the
      lens aperture, which partitions the pupil and leads to an extended depth of
      field. This system is analyzed by diffraction and random process theory.
      Experiments are reported that are in good agreement with the theory.

PMID- 19104544
TI  - Robust autonomous detection of the defective pixels in detectors using a
      probabilistic technique.
AB  - Detection of defective pixels in solid-state detectors/sensor arrays has received
      limited research attention. Few approaches currently exist for detecting the
      defective pixels using real images captured with cameras equipped with such
      detectors, and they are ad hoc and limited in their applicability. In this paper,
      we present a probabilistic novel integrated technique for autonomously detecting
      the defective pixels in image sensor arrays. It can be applied to images
      containing rich scene information, captured with any digital camera equipped with
      a solid-state detector, to detect different kinds of defective pixels in the
      detector. We apply our technique to the detection of various defective pixels in
      an experimental camera equipped with a charge coupled device (CCD) array and two
      out of the four HgCdTe detectors of the UKIRT's wide field camera (WFCAM) used
      for infrared (IR) astronomy [Astron. Astrophys.467, 777-784 (2007)].

PMID- 19104545
TI  - Polarization insensitive wavelength conversion for 4x112Gbit/s polarization
      multiplexing RZ-QPSK signals.
AB  - In this paper, polarization-insensitive wavelength conversion based on orthogonal
      pumps and four-wave mixing in HNLF is experimentally demonstrated for high-speed
      112-Gb/s PolMux-RZ-QPSK transmission with digital coherent detection. The
      conversion performance of the proposed scheme is investigated for both single-
      and four-channel input signals, with the achieved post-conversion OSNR for the
      two cases shown to be 30 and 20 dB, respectively. Moreover, it is shown that the
      OSNR of the converted single-channel signal can be maintained above 25 dB even if
      the wavelength spacing between the original and converted signals is larger than
      25 nm. Finally, the BER of 4x112-Gb/s PolMux-RZQPSK converted signals after 1 km
      HNLF transmission is measured to be below 1x10(-4). The optimum OSNR and launched
      HNLF power are also investigated.

PMID- 19104546
TI  - Simulation of an oil immersion objective lens: a simplified ray-optics model
      considering Abbe's sine condition.
AB  - In this paper, a simplified mathematical ray-optics model for an oil immersion
      objective lens, considering Abbe's sine condition, is presented. Based on the
      given parameters of the objective lens, the proposed model utilizes an approach
      based on a paraxial thin lens formulation. This is done to simplify the
      complexity of the objective lens by avoiding the consideration of many lens
      elements inside a single objective lens. To demonstrate the performance of the
      proposed model, comparisons with exact ray tracing method, based on the
      specification of real objective lens, are presented in terms of several different
      criteria including the variation of shape of the light cone, the extent of
      vignetting and the focus displacement. From the exemplary simulations, it was
      demonstrated that the proposed model can describe the focusing of light through
      the objective lens precisely, even when the incident beam rotates.

PMID- 19104547
TI  - Efficiency improvement and image quality of organic light-emitting display by
      attaching cylindrical microlens arrays.
AB  - In this paper, cylindrical microlens arrays with two different alignments were
      proposed to be applied in a commercial mobile phone having an organic light
      emitting diode (OLED) panel. It was found that the parallel-aligned cylindrical
      array had better performance than the vertical-aligned one for the OLED panel.
      The parallel-aligned cylindrical microlens array can increase the luminous
      current efficiency at surface normal and the luminous power efficiency of the
      OLED panel by 45% and 38%, respectively. Besides, it can also make the spectrum
      of the OLED panel more insensitive to the viewing angle. Though it can slightly
      blur the image on the OLED panel, the universal image quality index can be
      maintained at a level of 0.8630.

PMID- 19104548
TI  - A passively mode-locked femtosecond soliton fiber laser at 1.5 microm with a CNT
      doped polycarbonate saturable absorber.
AB  - We report a new 1.5 mum femtosecond fiber soliton laser incorporating a polymer
      saturable absorber that consists of polycarbonate (PC) with carbon nanotubes
      (CNTs). We installed the polymer in a fiber laser with a cavity length of 5.1 m,
      in which an erbium-doped fiber was used as the gain medium. Stable passive mode
      locking was achieved for a pump power of 303 mW at 39 MHz, and a pulse width of
      115 fs with an average output power of 3.4 mW was obtained.

PMID- 19104549
TI  - Ocular aberrations up to the infrared range: from 632.8 to 1070 nm.
AB  - Ocular aberrations were measured by using a Hartmann-Shack wavefront sensor in
      the visible and infrared portions of the spectrum. In the latter, wavelengths
      1030, 1050 and 1070 nm were used for the first time for the study of the optical
      quality of the eye. In this spectral range the retinal photoreceptors barely
      respond, so the radiation is virtually invisible for the subject. The results
      were confronted with those obtained by the same system at 780 and 632.8 nm.
      Monochromatic aberrations were found to be similar from the visible to the
      infrared. Longitudinal chromatic aberration was experimentally obtained, being
      approximately 1 D from 632.8 to 1070 nm. The feasibility of using the infrared
      for studying the eye was demonstrated. The employment of the infrared has an
      enormous potential for the better understanding of the impact and influence of
      the aberrations in vision with adaptive optics. It allows for measuring and
      controlling aberrations whilst the subject might eventually perform visual tests,
      with no interference from the beacon light.

PMID- 19104550
TI  - Nonlinear plasmonic slot waveguides.
AB  - We study nonlinear modes in a subwavelength slot waveguide created by a nonlinear
      dielectric slab sandwiched between two metals. We present the dispersion diagrams
      of the families of nonlinear guided modes and reveal that the symmetric mode
      undergoes the symmetry-breaking bifurcation and becomes primarily localized near
      one of the interfaces. We also find that the antisymmetric mode may split into
      two brunches giving birth to two families of nonlinear antisymmetric modes.

PMID- 19104551
TI  - Optical source transformations.
AB  - Transformation optics is a recently appreciated methodology for the design of
      complex media that control the propagation of electromagnetic and other types of
      waves. The transformation optical technique involves the use of coordinate
      transformations applied to some region of space, providing a conceptual means to
      redirect the flow of waves. Successfully designed devices to date have made use
      of transformations acting on passive space only; however, the technique can also
      be applied when source distributions (e.g., current and charge) are included
      within the space being transformed. In this paper we present examples of source
      transformations that illustrate the potential of these expanded transformation
      optical methods. In particular, using finite-element full-wave simulations, we
      confirm the restoration of dipole radiation patterns from both a distorted 'pin
      wheel' antenna and a bent dipole partially occluded by a cylindrical scatterer.
      We propose the technique of source transformations as a powerful approach for
      antenna design, especially in relation to conformal antennas.

PMID- 19104552
TI  - Non-linear corrections to aberration sensitivity of unstable-cavity geometries.
AB  - The aberration sensitivity of unstable-cavity geometries is studied by
      incorporating the change of the ray path by the intra-cavity aberrations in
      geometric-optic approximation. The first order non-linear correction in a
      positive branch, confocal unstable cavity is obtained analytically. In
      particular, as the optic field passes through an aberration plane in which the
      higher order aberrations are presented, more higher order aberrations are induced
      on the wavefront of optic field, and the original transverse modes are mixed.
      This mode mixing is studied by introducing non-constant propagation matrices.
      Similar to the linear results, we find that the non-linear corrections to
      aberration sensitivity decreases when geometric magnification or aberration
      orders increase.

PMID- 19104553
TI  - Three-dimensional optical metamaterials as model systems for longitudinal and
      transverse magnetic coupling.
AB  - In this paper, we demonstrate that metamaterials represent model systems for
      longitudinal and transverse magnetic coupling in the optical domain. In
      particular, such coupling can lead to fully parallel or antiparallel alignment of
      the magnetic dipoles at the lowest frequency resonance. Also, we present the
      design scheme for constructing three-dimensional metamaterials with solely
      magnetic interaction. Our concept could pave the way for achieving rather
      complicated magnetic materials with desired arrangements of magnetic dipoles at
      optical frequencies.

PMID- 19104554
TI  - Study of spectral and annealing properties of fiber Bragg gratings written in H2
      free and H2- loaded fibers by use of femtosecond laser pulses.
AB  - The spectral and annealing properties of a series of fiber Bragg gratings (FBGs)
      written in both H(2)-loaded and H(2)-free fibers by use of 800nm femtosecond
      laser pulse irradiation and created through a phase mask, have been investigated.
      It is found that type II FBGs inscribed in H(2)- loaded fibers exhibit superior
      spectral quality when compared with those written in H(2)-free fibers. Isochronal
      annealing tests shows that type II FBGs written in H(2)-free fibers have the
      highest thermal stability, followed (in order of stability) by H(2)-loaded type
      II, H(2)-free type I and then H(2)-loaded type I FBGs. The thermal stability of
      the H(2)-loaded type II FBGs can effectively be increased by using a high
      temperature pre-annealing treatment. After the treatment, type II FBGs written
      into both H(2)-free and H(2)-loaded fibers can sustain long-term annealing (for
      more than 12 hours) at temperatures of more than 1000 masculineC while their high
      reflectivities can still be maintained. This demonstrates the real potential of
      the FBGs developed and investigated in this work to be used as the ideal sensing
      elements for a series of high temperature measurement applications.

PMID- 19104555
TI  - Thermal lens and interferometric method for glass transition and thermo physical
      properties measurements in Nd2O3 doped sodium zincborate glass.
AB  - In this work the time resolved thermal lens method is combined with
      interferometric technique, the thermal relaxation calorimetry, photoluminescence
      and lifetime measurements to determine the thermo physical properties of
      Nd(2)O(3) doped sodium zincborate glass as a function of temperature up to the
      glass transition region. Thermal diffusivity, thermal conductivity, fluorescence
      quantum efficiency, linear thermal expansion coefficient and thermal coefficient
      of electronic polarizability were determined. In conclusion, the results showed
      the ability of thermal lens and interferometric methods to perform measurements
      very close to the phase transition region. These techniques provide absolute
      values for the measured physical quantities and are advantageous when low scan
      rates are required.

PMID- 19104556
TI  - High-frequency response of subwavelength-structured metals in the petahertz
      domain.
AB  - Electromagnetic plane waves, incident on and reflecting from a dielectric
      conductor interface, set up a standing wave in the dielectric with the B-field
      adjacent to the conductor. It is shown here how the harmonic time variation of
      this B-field induces an E-field and a conduction current J (c) within the skin
      depth of a real metal; and that at frequencies in the visible and near-infrared
      range, the imaginary term sigmai of the complex conductivity sigma = sigma(r) +
      isigma(i) dominates the optical response. Continuity conditions of the E-field
      through the surface together with the in-quadrature response of the conductivity
      determine the phase relation between the incident E-M field and J(c). If slits or
      grooves are milled into the metal surface, a displacement current in the
      dielectric gap and oscillating charge dipoles at the structure edges are
      established in quadrature phase with incident field. These dipoles radiate into
      the aperture and launch surface waves from the edges. They are the principle
      source of light transmission through the apertures.

PMID- 19104557
TI  - The role of leaky plasmon waves in the directive beaming of light through a
      subwavelength aperture.
AB  - We show that the enhanced directivity phenomenon for light passing through a
      subwavelength aperture in a silver film with corrugations on the exit face, is
      due to a leaky wave that decays exponentially from the aperture. We show
      quantitatively that the field along the interface of the silver film is dominated
      by the leaky wave, and that the radiation of the leaky wave, supported by the
      periodic structure, yields the directive beam. The leaky wave propagation and
      attenuation constants parameterize the physical radiation mechanism, and provide
      important design information for optimizing the structure. Maximum directivity
      occurs when the phase and attenuation constants are approximately equal.

PMID- 19104558
TI  - Modeling thermal effects and polarization competition in vertical-cavity surface
      emitting lasers.
AB  - We analyze the influence of thermal effects on the polarization-resolved light
      current (LI) characteristics of verticalcavity surface-emitting lasers (VCSELs).
      We use a model that is an extension of the spin-flip model incorporating material
      gain that is frequency and temperature dependent, and a rate equation for the
      temperature of the active region, which takes into account decay to a fixed
      substrate temperature, Joule heating and nonradiative recombination heating. The
      model also incorporates the red shift for increasing temperature of the gain
      curve and of the cavity resonance. The temperature sensitivity of the lasing
      threshold current is found to be in good qualitative agreement with observations
      and with previous reports based on detailed microscopic models. The temperature
      dependence of the polarization switching point, when the dominant polarization
      turn off and the orthogonal polarization emerges, is characterized in terms of
      various model parameters, such as the room-temperature gain-cavity offset, the
      subtracte temperature, and the size of the active region.

PMID- 19104559
TI  - Design and simulation of few-cycle optical parametric chirped pulse amplification
      at mid-IR wavelengths.
AB  - We present a design for a novel carrier to envelope phase stable optical
      parametric chirped pulse amplification source in the mid-infrared. We calculate
      the amplification of a 3.1 microm seed pulse, generated via DFG from a two-colour
      fibre laser, using a fully three dimensional OPCPA code. We combine this with a
      ray-tracing code to model pulse compression using a grating compressor and a
      deformable mirror for programmable phase compensation. The simulation models the
      complete system based on FROG measurements of the commercially available fibre
      laser, ensuring the simulation is realistic. The obtained results indicate
      energetic pulses of 56 fs duration, corresponding to 5.2 cycles, can be produced
      with calculated pulse energies of up to 9.6 microJ at a central wavelength of 3.3
      microm.

PMID- 19104560
TI  - Mechanical modulation method for ultrasensitive phase measurements in photonics
      biosensing.
AB  - A novel polarimetry methodology for phase-sensitive measurements in single
      reflection geometry is proposed for applications in optical transduction-based
      biological sensing. The methodology uses altering step-like chopper-based
      mechanical phase modulation for orthogonal s- and p- polarizations of light
      reflected from the sensing interface and the extraction of phase information at
      different harmonics of the modulation. We show that even under a relatively
      simple experimental arrangement, the methodology provides the resolution of phase
      measurements as low as 0.007 deg. We also examine the proposed approach using
      Total Internal Reflection (TIR) and Surface Plasmon Resonance (SPR) geometries.
      For TIR geometry, the response appears to be strongly dependent on the prism
      material with the best values for high refractive index Si. The detection limit
      for Si-based TIR is estimated as 10(-5) in terms Refractive Index Units (RIU)
      change. SPR geometry offers much stronger phase response due to a much sharper
      phase characteristics. With the detection limit of 3.2*10(-7) RIU, the proposed
      methodology provides one of best sensitivities for phase-sensitive SPR devices.
      Advantages of the proposed method include high sensitivity, simplicity of
      experimental setup and noise immunity as a result of a high stability modulation.

PMID- 19104562
TI  - Design of high-Q photonic crystal microcavities with a graded square lattice for
      application to quantum cascade lasers.
AB  - A high-Q photonic crystal (PC) microcavity for TM-like modes, which can be
      applied to quantum cascade lasers (QCLs), was successfully designed in an air
      hole based PC slab with semiconductor cladding layers. In spite of no photonic
      badgaps for TM-like modes in air-hole based PC slabs, cavity Q reached up to
      2,200 by utilizing a graded square lattice PC structure. This is approximately 18
      times higher than those previously reported for PC defect-mode microcavities for
      QCLs. This large improvement is attributed to a suppression of the coupling
      between the cavity mode and the leaky modes thanks to the dielectric perturbation
      in the graded structure. We also predicted a dramatic reduction of the threshold
      current in the designed cavity down to one-fifteenth of that of a conventional
      QCL, due to a decreased optical volume.

PMID- 19104561
TI  - Propagation of Bessel-Gaussian beams with optical vortices in turbulent
      atmosphere.
AB  - An approximate expression of a Bessel-Gaussian beam (BGB) with desired
      topological charge is introduced using a coherence superposition of decentered
      Gaussian beams (dGBs). And based on such an expression and the extended Huygens
      Fresnel principle, the propagation properties of BGBs traveling in turbulent
      atmosphere are explored. An analytical expression of the average intensity of a
      BGB with phase singularity propagating through turbulent atmosphere is obtained
      and analyzed numerically. It is found that intensity profiles of BGBs experienced
      successive variations and the phase singularity rapidly fades away during
      propagating in turbulent atmosphere.

PMID- 19104563
TI  - Optical properties of new wide heterogeneous waveguides with thermo optical
      shifters.
AB  - We present analysis and simulation of novel silicon-on-insulator (SOI)
      heterogeneous waveguides with thermo-optic phase shifters. New structure design
      contains a p-n junction on both sides of SOI ridge waveguide with 220 nm x 35
      microm silicon core. Strongly mode-dependent optical losses (by additional free
      charge absorption) provide quasi-singe-mode behavior of wide waveguide with mode
      size approximately 10 microm. Local heater produces an efficient phase shifting
      by small temperature increase (DeltaT approximately 2K), switching power (< 40
      mW) and switching time (< 10 micros). Mode optical losses are significantly
      decreased at high heating (DeltaT approximately 120 K).

PMID- 19104564
TI  - Mueller matrix retinal imager with optimized polarization conditions.
AB  - A new Mueller matrix polarimeter was used to image the retinas of normal
      subjects. Light from a linearly polarized 780 nm laser was passed through a
      system of variable retarders and scanned across the retina. Light returned from
      the eye passed through a second system of retarders and a polarizing beamsplitter
      to two confocal detection channels. Optimization of the polarimetric data
      reduction matrix was via a condition number metric. The accuracy and
      repeatability of polarization parameter measurements were within +/- 5%. The
      magnitudes and orientations of retardance and diattenuation, plus depolarization,
      were measured over 15 degrees of retina for 15 normal eyes.

PMID- 19104565
TI  - Characteristic investigation of 2D photonic crystals with full material
      anisotropy under out-of-plane propagation and liquid-crystal-filled photonic-band
      gap-fiber applications using finite element methods.
AB  - To effectively investigate the fundamental characteristics of two-dimensional
      (2D) photonic crystals (PCs) with arbitrary 3D material anisotropy under the out
      of-plane wave propagation, we establish a full-vectorial finite element method
      based eigenvalue algorithm to perform related analysis correctly. The band edge
      diagrams can be conveniently constructed from the band structures of varied
      propagation constants obtained from the algorithm, which is helpful for the
      analysis and design of photonic ban gap (PBG) fibers. Several PCs are analyzed to
      demonstrate the correctness of this numerical model. Our analysis results for
      simple PCs are checked with others' ones using different methods, including the
      transfer matrix method, the finite-difference frequency-domain (FDFD) method, and
      the plane-wave expansion method. And the validity of those for the most complex
      PC with arbitrary 3D anisotropy is supported by related liquid-crystal-filled PBG
      fiber mode analysis, which demonstrates the dependence of transmission properties
      on the PBGs, employing a full-vectorial finite element beam propagation method
      (FE-BPM).

PMID- 19104566
TI  - Ideal and nonideal invisibility cloaks.
AB  - We employ the analytical solutions for the spatial transformation of the
      electromagnetic fields to obtain and analyze explicit expressions for the
      structure of the electromagnetic fields in invisibility cloaks. Similar approach
      can be also used for analyzing beam splitters and field concentrators. We study
      the efficiency of nonideal electromagnetic cloaks and discuss the effect of
      scattering losses on the cloak invisibility.

PMID- 19104567
TI  - Investigation of extraordinary optical transmission and Faraday effect in one
      dimensional metallic-magnetic gratings.
AB  - We have investigated extraordinary optical transmission (EOT) with enhanced
      Faraday effect in one-dimensional metallic-magnetic slit arrays under polar
      magnetization using the rigorous coupled-wave analysis performed by the Airy-like
      internal reflection series. The roles of surface plasmon polaritons and quasi
      guided waves are studied in which the latter plays a key role. Based on the
      mechanism of EOT with an enhanced Faraday effect, both enhanced transmittance and
      enhanced Faraday effect are optimized by adjusting the geometric parameters of
      slit arrays evaluated by the figure of merit.

PMID- 19104568
TI  - Accurate measurement of carrier-envelope phase drift for infrared femtosecond
      laser pulses.
AB  - A novel scheme to eliminate the artificial background phase jitter is proposed
      for measuring the carrier-envelope phase drift of tunable infrared femtosecond
      pulses from an OPA laser. Different from previous methods, a reference spectral
      interference measurement is performed, which reveals the artificial phase jitter
      in the measurement process, in addition to the normal f-to-2f interference
      measurement between the incident laser pulses and it second harmonic. By
      analyzing the interference fringes, the accurate CEP fluctuation of the incident
      pulses is obtained.

PMID- 19104569
TI  - Imaging through turbid media based on wave transport model approach.
AB  - Here a transport model is used to simulate amplitude-only imaging and intensity
      based quantitative phase imaging in a turbid medium. We derive an optical
      transfer function for propagation through a scattering medium. We also show that,
      as expected, scattering leads to a degradation in the spatial resolution in both
      forms of imaging, while the magnitude of the phase retrieved using a solution of
      the transport-of-intensity equation decreases as the optical density of the
      scattering medium increases.

PMID- 19104570
TI  - Synthesis of a multichannel lattice-form optical delay-line circuit with ring
      waveguides.
AB  - This paper presents a one-input M -output (1 x M) circuit configuration and a
      synthesis algorithm for realizing an optical infinite impulse response (IIR)
      lattice filter having M -output channels (M > or =2) .The circuit configuration
      has a multilayer structure consisting of multiple Mach-Zehnder interferometers
      with delay time difference of Deltatau. It is a natural extension of the
      conventional two-port optical IIR lattice circuit (M =2) . Synthesis algorithm is
      derived to obtain all unknown circuit parameters. The proposed synthesis
      algorithm is based on factorizations of the paraunitary total transfer matrix.
      Simulation result demonstrates the effectiveness of the proposed multichannel IIR
      design scheme. The synthesis algorithm for M - channel IIR filter is considered
      lossless in this paper, which implies that the filter must be power
      complementary.

PMID- 19104571
TI  - Evaluation of the monocular depth cue in 3D displays.
AB  - Binocular disparity and monocular depth information are the principal functions
      of ideal 3D displays. 3D display systems such as stereoscopic or multi-view,
      super multi-view (SMV), and multi-focus (MF) displays were considered for the
      testing of the satisfaction level with the monocular accommodation of three
      different depths of 3D object points. The numerical simulation and experimental
      results show that the MF 3D display gives a monocular depth cue. In addition, the
      experimental results of the monocular MF 3D display show clear monocular focus on
      four different depths. Therefore, we can apply the MF 3D display to monocular 3D
      displays.

PMID- 19104572
TI  - Data-thinning algorithms for "over-sampled" multi-parameter ocean optics data.
AB  - The deployment of towed depth-profiling paravane systems and autonomous gliders
      is providing a wealth of high-resolution oceanographic datasets. These datasets
      are, however, over-sampled in space and time. This paper describes a data
      adaptive, user-configurable method that has been used to significantly reduce the
      time/space density of such data without compromising the inherent scientific
      information that they provide. The method involves sub-sampling at fixed space
      and time intervals with additional samples being kept given either a significant
      change (1) in the depth extent of the alongtrack profiles, or (2) in the values
      of the profiles themselves. An example is provided showing how well the algorithm
      works on nearly 5,000 chlorophyll fluorescence profiles collected off the coast
      of Australia.

PMID- 19104574
TI  - Phase-sensitive amplification using gain saturation in a nonlinear Sagnac
      interferometer.
AB  - Phase-sensitive amplification of picosecond optical pulses was demonstrated using
      an SOA as the nonlinear medium inside a Sagnac interferometer. Ratios of maximum
      to minimum gain of more than 3:1 were experimentally measured. Numerical
      simulations using a semiconductor amplifier model are consistent with
      experiments.

PMID- 19104573
TI  - Remote plethysmographic imaging using ambient light.
AB  - Plethysmographic signals were measured remotely (> 1m) using ambient light and a
      simple consumer level digital camera in movie mode. Heart and respiration rates
      could be quantified up to several harmonics. Although the green channel featuring
      the strongest plethysmographic signal, corresponding to an absorption peak by
      (oxy-) hemoglobin, the red and blue channels also contained plethysmographic
      information. The results show that ambient light photo-plethysmography may be
      useful for medical purposes such as characterization of vascular skin lesions
      (e.g., port wine stains) and remote sensing of vital signs (e.g., heart and
      respiration rates) for triage or sports purposes.

PMID- 19104575
TI  - Cascade wide-angle Y-junction 1 x 16 optical power splitter based on silicon wire
      waveguides on silicon-on-insulator.
AB  - A 1 x 16 optical power splitter with wide splitting angle, uniform outputs, and
      low excess loss is demonstrated. The 1 x 16 splitter comprising cascaded 1 x 2
      splitters with arc-shaped branching waveguides is fabricated on the silicon-on
      insulator (SOI) substrate. The gap between the branching waveguides is widened in
      a short propagation length such that influences of etch residues and air voids in
      the gap on the optical power uniformity are reduced significantly. The measured
      power uniformity of the 1 x 16 splitter is better than 0.3 dB at wavelength of
      1550 nm.

PMID- 19104576
TI  - Quantum nondemolition measurement of photon number via optical Kerr effect in an
      ultra-high-Q microtoroid cavity.
AB  - We theoretically investigate a quantum nondemolition (QND) measurement with
      optical Kerr effect in an ultra-high-Q microtoroidal system. The analytical and
      numerical results predict that the present QND measurement scheme possesses a
      high sensitivity, which allows for detecting few photons or even single photons.
      Ultra-high-Q toroidal microcavity may provide a novel experimental platform to
      study quantum physics with nonlinear optics at low light levels.

PMID- 19104577
TI  - Effective thermo-optical enhanced cross-ring resonator MZI interleavers on SOI.
AB  - A cross-ring (CR-) Mach-Zehnder interferometer (MZI) interleaver structure has
      been proposed and fabricated. It uses an '8' shaped cross-ring resonator to
      replace the conventional circular ring resonator. Thus, the new structure can
      have the function of add-signal. Furthermore, a thermo-optical fine tuning has
      been applied, which improves the crosstalk performance from approximately -10 dB
      to approximately -20 dB with 9 V applied on the heater of the 3-dB directional
      coupler.

PMID- 19104578
TI  - Gamma-Mu waveguides in two-dimensional triangular-lattice photonic crystal slabs.
AB  - We propose a line defect waveguide structure along the Gamma-Mu direction in two
      dimensional triangular lattice silicon photonic crystal slabs. The modal
      dispersion relation and the transmission spectra of this waveguide are studied.
      The results show that by perturbing the width of the line defect and the diameter
      of the air holes adjacent to the waveguide core, one can control the width of the
      single mode transmission window and make it far broader than the original one.
      The proposed Gamma-Mu waveguide will help to build a more flexible network of
      interconnection channel of light in two-dimensional photonic crystal slabs.

PMID- 19104579
TI  - Image contrast enhancement in angular domain optical imaging of turbid media.
AB  - Imaging structures within a turbid medium using Angular Domain Imaging (ADI)
      employs an angular filter array to separate weakly scattered photons from those
      that are highly scattered. At high scattering coefficients, ADI contrast declines
      due to the large fraction of non-uniform background scattered light still within
      the acceptance angle. This paper demonstrates various methods to enhance the
      image contrast in ADI. Experiments where a wedge prism was used to deviate the
      laser source so that scattered photons could be imaged and subtracted from the
      image obtained by standard ADI provided the greatest improvement in image
      contrast.

PMID- 19104580
TI  - Efficient double-filtering with a single acousto-optic tunable filter.
AB  - We describe an efficient double-filtering method that uses a single acousto-optic
      tunable filter (AOTF) to improve the spectral resolution and intrinsic sidelobes
      for the spectral domain analysis systems. Double filtering with a single AOTF is
      realized by applying a unique feedback scheme based on the fact that incident
      light can be diffracted into two orthogonally polarized beams of light by an
      AOTF. Our theoretical explanation attempts to address and satisfy the main
      prerequisite for the proposed idea. The experimental results confirm that the
      proposed method achieves a 20% to 30% improvement in spectral resolution and 10
      dB suppression of sidelobes with minimized light loss for the extraordinary
      incident light. We believe that the results of using an AOTF are comparable to
      the results achieved with two AOTFs in tandem.

PMID- 19104581
TI  - Attempts to grow optically coupled Fibonacci-spaced InGaAs/GaAs quantum wells
      result in surface gratings.
AB  - An instability in the growth of nonperiodic InGaAs/GaAs multiple quantum well
      samples, ordinarily of high-quality when grown with equal periods of order of
      half the wavelength of light in the material, leads to a dramatic microscopic,
      self-organized surface grating. This effect was discovered while growing quantum
      wells with two unequal barrier lengths arranged in a Fibonacci sequence to form
      an optical quasicrystal. A laser beam incident normal to the surface of the
      sample is diffracted into a propeller-shaped pattern. The sample surface has a
      distinctly cloudy appearance when viewed along one crystal axis but is mirror
      like when the sample is rotated 90 degrees. The instability results in a five
      fold increase in the absorption linewidth of the heavy-hole exciton transition.
      Atomic force microscopy, transmission electron microscopy, and scanning electron
      microscopy were used to study the samples.

PMID- 19104582
TI  - Reduction of patterning effects in SOA-based wavelength converters by combining
      cross-gain and cross-absorption modulation.
AB  - A scheme for mitigating patterning effects in wavelength conversion by using a
      concatenated semiconductor optical amplifier (SOA) and electroabsorption
      modulator (EAM) is proposed. The optimization of the parameters of the
      semiconductor devices and receiver electronics is theoretically investigated. The
      bit error ratio (BER) of the output signals in both the co-propagating and the
      counter-propagating configurations is quantitatively evaluated. The simulation
      results indicate that the patterning effect in wavelength conversion due to the
      slow recovery of the carrier density in the SOA can be well compensated by a
      concatenated EAM. The simulation results are confirmed by preliminary pump-probe
      experiment using a 10Gb/s clock pulse train.

PMID- 19104583
TI  - Self-compression of 2 microm laser filaments.
AB  - We numerically study the filamentation of ultrashort laser pulses at 2 microm
      carrier wavelength in noble gases (argon, xenon) and in air. Compared with
      filamentation in the near-visible domain (800 nm), mid-infrared optical sources
      with durations close to a single cycle can be generically produced at various
      pressures and powers near the self-focusing threshold. The mechanism by which
      self-compression takes place mainly involves optical self-focusing, pulse
      steepening and plasma defocusing. On-axis spectra and spectral phases are
      discussed. Delivering single-cycled pulses at long wavelengths has important
      applications in the generation of high-order harmonics and isolated attosecond
      pulses.

PMID- 19104584
TI  - Expanding the band of negative permeability of a composite structure with dual
      band negative permeability.
AB  - We provide a design of a metallic composite structure, which simultaneously shows
      dual-band negative permeability (DNP) in two optical ranges. Numerical simulation
      demonstrates that different shifting of the two magnetic resonances can be
      observed. This structure property allows the realization of a wide range of
      negative permeability covering near-infrared (NIR) and visible ranges
      simultaneously. The alterability of the two neighboring negative permeability
      would provide a way to realize an effective pass-band of a meta-material with
      negative permeability at optical frequencies.

PMID- 19104585
TI  - Novel custom fiber Bragg grating fabrication technique based on push-pull phase
      shifting interferometry.
AB  - A new UV-writing technique is proposed for fabricating custom fiber Bragg
      gratings (FBGs). A continuously moving fringe pattern is generated by use of two
      electro-optical UV modulators and synchronized with a moving fiber. This scheme
      potentially enables the fabrication of infinitely long FBGs with arbitrary
      profiles and chirp without any mechanical perturbation of the writing
      interferometer. Preliminary results of this technique are presented and
      discussed.

PMID- 19104586
TI  - Multiple reflection Michelson interferometer with picometer resolution.
AB  - A Michelson interferometer based on an optical set-up allowing multiple
      reflection between two plane mirrors performs the multiplication of the optical
      path by a factor N, proportionally increasing the resolution of the measurement.
      A multiplication factor of almost two orders of magnitude has been demonstrated
      with a simple set-up. The technique can be applied to any interferometric
      measurement where the classical interferometer limits due to fringe
      nonlinearities and quantum noise are an issue. Applications in precision
      engineering, vibration analysis, nanometrology, and spectroscopy are foreseen.

PMID- 19104587
TI  - 20 GHz arbitrary radio-frequency waveform generator based on incoherent pulse
      shaping.
AB  - We demonstrate a new approach of photonically assisted radio-frequency (RF)
      waveform generation using a spectrally incoherent light source. The system is
      based on the so-called generalized frequency-to-time mapping operation. In this
      work, external modulation of the source is done by concatenating two electro
      optic Mach-Zehnder modulators properly biased to achieve short pulse gates which
      allow for broad bandwidth electrical signals. Also, the spectral shaping stage is
      performed prior to O/E conversion. A detailed theoretical analysis demonstrates
      that even in this case the frequency-to-time mapping is preserved. The key is
      that the noise level is greatly reduced because the amplitude filter serves as
      noise rejecter. Experimental results show up to approximately 20 GHz electrical
      bandwidth signals using 10 Gb/s standard telecommunication equipment with the
      nice feature of repetition rate control on the generated electrical waveform.

PMID- 19104588
TI  - Four-dimensional photoacoustic imaging of moving targets.
AB  - Photoacoustic imaging provides optical contrast with improved tissue penetration
      and spatial resolution compared to pure optical techniques. Three-dimensional
      photoacoustic imaging is particularly advantageous for visualizing non-planar
      light absorbing structures, such as blood vessels, internal organs or tumours. We
      have developed a fast 3-D photoacoustic imaging system for small animal research
      based on a sparse array of ultrasonic detectors and iterative image
      reconstruction. The system can acquire 3-D images with a single laser-shot at a
      frame rate of 10 Hz. To demonstrate the imaging capabilities we have constructed
      phantoms made of a scanning point source and a rotating line object and imaged
      them at a rate of 10 frames per second. The resulting 4-D photoacoustic images
      depicted well the motion of each target. Comparison of the perceived motion in
      the images with the known velocity of the target showed good agreement. To our
      knowledge, this is the first report of single-shot high frame-rate 3-D
      photoacoustic imaging system. With further developments, this system could bring
      to bear its inherent speed for applications in small animal research, such as
      motion tracking of tumour outline during respiration, and rapid monitoring of
      contrast agent kinetics.

PMID- 19104589
TI  - Greatly enhanced modulation response of injection-locked multimode VCSELs.
AB  - We report greatly enhanced modulation response of multimode vertical-cavity
      surface-emitting lasers (MM-VCSELs), for the first time, using optical injection
      locking. A 3-dB bandwidth of 38 GHz and 54 GHz resonance frequency are achieved
      using a MM-VCSEL with a 3 GHz free-running bandwidth. We show that transverse
      mode selection can be attained with optical injection locking through frequency
      and spatial detuning.

PMID- 19104590
TI  - An optical-fiber-scale electro-optic probe for minimally invasive high-frequency
      field sensing.
AB  - A sub-millimeter-dimension electro-optic probe that provides enhanced scanning
      accessibility with significantly less intrusiveness than metal-based or even
      other dielectric probes during electromagnetic characterization of microwave
      devices is presented. The quantitative and qualitative relative invasiveness of
      the probe on the operation of an example antenna device-under-test is explored
      with respect to previously demonstrated fiber and wafer electro-optic sensors. We
      also demonstrate that the miniaturized probe, with a diameter of 125 microm, can
      be used to reconstruct the three orthogonal vector components of near-electric
      fields without the need for different probe crystals or multiple calibration
      procedures. Finally, the advantages of the reduced size and invasiveness of the
      new micro-scale probe are demonstrated through the enhanced resolution of
      detailed images extracted from planar antennas, as well as the capability of
      reaching into circuit locations heretofore inaccessible.

PMID- 19104591
TI  - Experimental and theoretical analysis of core-to-core coupling on fiber bundle
      imaging.
AB  - Flexible endoscopes commonly use coherent fiber bundles with high core density to
      facilitate in vivo imaging. Small, closely spaced cores are desired for achieving
      a high number of resolvable pixels in a small diameter fiber bundle. On the other
      hand, closely spaced cores potentially lead to strong core-to-core coupling.
      Based on numerical simulations, it was previously explained that image fiber
      bundles can successfully transmit images because of nonuniformities in the core
      size that reduce coupling. In this paper, we show numerically and experimentally
      that, due to the randomness of the structural nonuniformity, significant core-to
      core coupling still exists in fiber bundles that are routinely used for imaging.
      The coupling is highly dependent on the illumination wavelength and polarization
      state. We further show that the resolution achievable by a fiber bundle depends
      not only on the core density, but also on the inter-core coupling strength.
      Finally, we propose that increasing the core-cladding index contrast is a
      promising approach to achieve a fiber bundle with low core coupling, high core
      density, and effectively single moded propagation in individual cores.

PMID- 19104592
TI  - Trapping light with micro lenses in thin film organic photovoltaic cells.
AB  - We demonstrate a novel light trapping configuration based on an array of micro
      lenses in conjunction with a self aligned array of micro apertures located in a
      highly reflecting mirror. When locating the light trapping element, that displays
      strong directional asymmetric transmission, in front of thin film organic
      photovoltaic cells, an increase in cell absorption is obtained. By recycling
      reflected photons that otherwise would be lost, thinner films with more
      beneficial electrical properties can effectively be deployed. The light trapping
      element enhances the absorption rate of the solar cell and increases the
      photocurrent by as much as 25%.

PMID- 19104593
TI  - Differential pulse-width pair BOTDA for high spatial resolution sensing.
AB  - A differential pulse-width pair Brillouin optical time domain analysis (DPP
      BOTDA) for centimeter spatial resolution sensing using meter equivalent pulses is
      proposed. This scheme uses the time domain waveform subtraction at the same
      scanned Brillouin frequency obtained from pulse lights with different pulse
      widths (e.g. 50ns and 49ns) to form the differential Brillouin gain spectrum
      (BGS) at each fiber location. The spatial resolution is defined by the average of
      the rise and fall time equivalent fiber length for a small stress section rather
      than the pulse-width difference equivalent length. The spatial resolution of
      0.18m for the 50/49ns pulse pair and 0.15m for 20/19ns pulse pair over 1km
      sensing length with Brillouin frequency shift accuracy of 2.6MHz are
      demonstrated.

PMID- 19104594
TI  - Leaky-mode assisted fluorescence extraction: application to fluorescence
      enhancement biosensors.
AB  - Efficient recovery of light emitted by fluorescent molecules by employing
      photonic structures can result in high signal-to-noise ratio detection for
      biological applications including DNA microarrays, fluorescence microscopy and
      single molecule detection. By employing a model system comprised of colloidal
      quantum dots, we consider the physical basis of the extraction effect as provided
      by photonic crystals. Devices with different lattice symmetry are fabricated
      ensuring spectral and spatial coupling of quantum dot emission with leaky
      eigenmodes and the emission characteristics are studied using angle-resolved and
      angle-integrated measurements. Comparison with numerical calculations and
      lifetime measurements reveals that the enhancement occurs via resonant
      redirection of the emitted radiation. Comparison of various lattices reveals
      differences in the enhancement factor with a maximum enhancement factor
      approaching 220. We also demonstrate the first enhanced extraction biosensor that
      allows for over 20-fold enhancement of the fluorescence signal in detection of
      the cytokine TNF-alpha by a fluorescence sandwich immunoassay.

PMID- 19104595
TI  - An analytical model for the illuminance distribution of a power LED.
AB  - Light-emitting diodes (LEDs) will play a major role in future indoor illumination
      systems. In general, the generalized Lambertian pattern is widely used as the
      radiation pattern of a single LED. In this letter, we show that the illuminance
      distribution due to this Lambertian pattern, when projected onto a horizontal
      surface such as a floor, can be well approximated by a Gaussian function.

PMID- 19104596
TI  - Adaptive threshold adjustment for signal-distortion-free digital-coherent optical
      demodulation system.
AB  - Optical quadrature amplitude modulation (QAM) attracts considerable attention in
      the enhancement of communications capacity, due to its high spectral efficiency.
      However, this modulation format is more sensitive to signal distortion than
      conventional formats, making it more difficult to create, transmit, and detect
      signals. In this paper, we propose an adaptive scheme for demodulation of the
      distorted optical signals with paying attention to use of DSP-technology. The
      scheme is based on the adjustment of the thresholds against the signal
      distortion. Successful demodulation of optical QAM signals is demonstrated with a
      sufficiently low bit-error rate.

PMID- 19104597
TI  - Nonlinear processes induced by the enhanced, evanescent field of surface plasmons
      excited by femtosecond laser pulses.
AB  - Evanescent fields of surface plasmon polaritons (SPP) above metal surfaces can
      reach 1-2 orders of magnitude higher, nearly atomic field strengths in comparison
      to the relatively weak exciting laser fields of a femtosecond Ti:sapphire laser
      oscillator. We used these high plasmonic fields to study the characteristic SPP
      phenomena of intense field optics experimentally. It was found that both the
      intensity and the angular distribution of SPP emitted light depend nonlinearly on
      the exciting laser intensity in the higher-intensity, non-perturbative range of
      the interactions. These results are supported by our theory. At these strong
      excitations, an additional, depolarized, diffuse spectrum also appeared which can
      be attributed either to the fluorescence of Au, or to the non-equlibrium Planck
      radiation, originating from the fast cooling of the conduction electron cloud of
      Au excited by the femtosecond laser pulse.

PMID- 19104598
TI  - High-contrast waveguides in sputtered pure TeO2 glass thin films.
AB  - We present a technological approach to the realization of channeled optical
      waveguides, starting from reactively sputtered tellurite glass thin films, grown
      on silica-coated 4" Si wafers. In particular, optical lithographic process and
      etching recipes have been developed to overcome the solubility of TeO(2) films in
      aqueous solutions, and to process them into high-index contrast structures with
      minimized post-etch roughness. Optical tests on preliminary rib waveguide
      geometries feature 6.3 dB/cm propagation loss for fundamental TE mode at lambda =
      1.5 microm.

PMID- 19104599
TI  - Polarization conversion through collective surface plasmons in metallic nanorod
      arrays.
AB  - For two-dimensional (2D) arrays of metallic nanorods arranged perpendicular to a
      substrate several methods have been proposed to determine the electromagnetic
      near-field distribution and the surface plasmon resonances, but an analytical
      approach to explain all optical features on the nanometer length scale has been
      missing to date. To fill this gap, we demonstrate here that the field
      distribution in such arrays can be understood on the basis of surface plasmon
      polaritons (SPPs) that propagate along the nanorods and form standing waves.
      Notably, SPPs couple laterally through their optical near fields, giving rise to
      collective surface plasmon (CSP) effects. Using the dispersion relation of such
      CSPs, we deduce the condition of standing-wave formation, which enables us to
      successfully predict several features, such as eigenmodes and resonances. As one
      such property and potential application, we show both theoretically and in an
      experiment that CSP propagation allows for polarization conversion and optical
      filtering in 2D nanorod arrays. Hence, these arrays are promising candidates for
      manipulating the light polarization on the nanometer length scale.

PMID- 19104600
TI  - Nanowire-based tunable photonic crystals.
AB  - Photonic crystals, materials with periodically varying refractive indices, show
      exciting optical properties that enable many technological applications.
      Conventional photonic crystals have optical properties that are determined at the
      time of fabrication and the ability to tune them is quite limited, particularly
      at visible frequencies. We investigate theoretically the possibility to use
      nanowires or nanotubes as the building block for tunable two-dimensional photonic
      crystals. Tunability is achieved by fabricating flexible nanowires in a periodic
      pattern and actuating them electrostatically. This changes the lattice basis,
      which in turn modifies the optical properties of the photonic crystal. We use a
      finite-difference time-domain method to model photonic crystals with changeable
      bases. We show that the optical transmission through a two-dimensional photonic
      crystal with only a few rows of nanowires in the light propagating direction can
      be electrostatically tuned from over 90% transmission to less than 10%. We
      demonstrate that tunability is maintained in realistic three-dimensional
      experimental geometries. Finally, we analyse the performance of the photonic
      crystals in terms of actuation voltages and tuning speeds, and conclude that the
      response time of a tunable carbon-nanofibre-based photonic crystal lies in the
      microsecond range.

PMID- 19104601
TI  - Vector analysis of stimulated Brillouin scattering amplification in standard
      single-mode fibers.
AB  - The polarization properties of stimulated Brillouin scattering (SBS)
      amplification or attenuation in standard single-mode fibers are examined through
      vectorial analysis, simulation and experiment. Vector propagation equations for
      the signal wave, incorporating SBS and birefringence, are derived and analyzed in
      both the Jones and Stokes spaces. The analysis shows that in the undepleted pump
      regime, the fiber may be regarded as a polarization-dependent gain (or loss)
      medium, having two orthogonal input SOPs, and corresponding two orthogonal output
      SOPs, for the signal, which, respectively, provide the signal with maximum and
      minimum SBS amplification (or attenuation). Under high Brillouin gain conditions
      and excluding zero-probability cases, the output SOP of arbitrarily polarized
      input signals, would tend to converge towards that of maximum SBS gain. In the
      case of high SBS attenuation the output SOP of an arbitrarily polarized signal
      would approach the output SOP corresponding to minimum attenuation. It is found
      that for a wide range of practical pump powers ( < or = 100mW) and for
      sufficiently long fibers with typical SBS and birefringence parameters, the
      signal aligned for maximum SBS interaction will enter/emerge from the fiber with
      its electric field closely tracing the same ellipse in space as that of the pump
      at the corresponding side of the fiber, albeit with the opposite sense of
      rotation. The analytic predictions are experimentally demonstrated for both
      Stokes (amplification) and anti-Stokes (attenuation) signals.

PMID- 19104602
TI  - Non-degenerated nonclassical photon pairs in a hot atomic ensemble.
AB  - We experimentally demonstrate the generation of non-degenerate nonclassical
      paired photons in a hot atomic ensemble using off-axis four-wave mixing. The time
      resolved second-order correlated function between the Stokes photon and the anti
      Stokes photon is given. The two-photon correlation between the photons obtained
      in this experiment is 1.87+/- 0.04, which leads to the violation of Cauchy
      Schwarz inequality by a factor of 1.69+/- 0.14.

PMID- 19104603
TI  - Quasi zero-background tunable diode laser absorption spectroscopy employing a
      balanced Michelson interferometer.
AB  - Tunable diode laser spectroscopy (TDLS) normally observes small fractional
      absorptive reductions in the light flux. We show, that instead a signal increase
      on a zero background can be obtained. A Michelson interferometer, which is
      initially balanced out in destructive interference, is perturbed by gas
      absorption in one of its arms. Both theoretical analysis and experimental
      demonstration show that the proposed zero-background TDLS can improve the
      achievable signal-to-noise ratio.

PMID- 19104604
TI  - Dynamic increase and decrease of photonic crystal nanocavity Q factors for
      optical pulse control.
AB  - We introduce recent advances in dynamic control over the Q factor of a photonic
      crystal nanocavity system. By carefully timing a rapid increase of the Q factor
      from 3800 to 22,000, we succeed in capturing a 4ps signal pulse within the
      nanocavity with a photon lifetime of 18ps. By performing an additional transition
      of the Q factor within the photon lifetime, the held light is once again ejected
      from of the system on demand.

PMID- 19104606
TI  - NIR femtosecond phase control of resonance-mediated generation of coherent UV
      radiation.
AB  - Shaped near-infrared (NIR) femtosecond pulses are used for the first time to
      control the generation of coherent deep-ultraviolet (UV) radiation in an atomic
      resonance-mediated (2+1) three-photon excitation. The broadband excitation
      coherently involves pathways that are on resonance with the intermediate
      resonance state as well as pathways that are near resonance with it. Experimental
      and theoretical results are presented for phase controlling the total emitted UV
      yield in atomic sodium. Depending on the NIR spectrum of the excitation pulse,
      the coherent UV emission is either predominantly due to a single excited real
      state that is accessed resonantly or due to a manifold of virtual states. The
      former leads to a narrowband UV emission, while the latter leads to a broadband
      UV radiation. Basic phase control is exercised in both cases, with excellent
      agreement between experiments and calculations. The tunability is over an order
      of-magnitude UV-yield range.

PMID- 19104605
TI  - Design and demonstration of a small-animal up-conversion imager.
AB  - This first small-animal up-conversion imager (SAUCI) was developed and used for
      in-vivo imaging of up-converting nanoparticles (UCNs.) Unlike traditional
      fluorophores, UCNs absorb multiple lower-energy photons and emit a single higher
      energy photon. This unique physical process makes it possible to image deeper
      into tissue with lower background signals. In vivo imaging of particle
      accumulation in the liver was demonstrated following intravenous injection of
      particles.

PMID- 19104607
TI  - Optical MEMS pressure sensor based on a mesa-diaphragm structure.
AB  - An optical MEMS pressure sensor based on a mesa-diaphragm is presented. The
      operating principle of the sensor is expatiated by Fabry-Perot (F-P)
      interference. Both the mechanical model and the signal averaging effect of the
      mesa diaphragm is validated by simulation, which declares that the mesa diaphragm
      is superior to the planar one on the parallelism and can reduce the signal
      averaging effect. Experimental results demonstrate that the mesa structure sensor
      has a reasonable linearity and sensitivity.

PMID- 19104608
TI  - Linear time-to-space mapping system using double electrooptic beam deflectors.
AB  - We propose and demonstrate a linear time-to-space mapping system, which is based
      on two times electrooptic sinusoidal beam deflection. The direction of each
      deflection is set to be mutually orthogonal with the relative deflection phase of
      pi/2 rad so that the circular optical beam trajectory can be achieved. The beam
      spot at the observation plane moves with an uniform velocity and as a result
      linear time-to-space mapping (an uniform temporal resolution through the mapping)
      can be realized. The proof-of-concept experiment are carried out and the temporal
      resolution of 5 ps has been demonstrated using traveling-wave type quasi-velosity
      matched electrooptic beam deflectors. The developed system is expected to be
      applied to characterization of ultrafast optical signal or optical arbitrary
      waveform shaping for modulated microwave/millimeter-wave generation.

PMID- 19104610
TI  - Optics for energy. Introduction.

PMID- 19104609
TI  - Bulk scattering approximations for HeNe laser transmitted through paper.
AB  - An experimental set-up was devised to record the transmission of red and green
      HeNe lasers through different types of paper. The measured data was compared with
      data obtained using the Henyey-Greenstein function (often employed in paper
      optics models to represent the bulk scattering of material samples) and data
      obtained using an alternative exponentiated cosine function. The comparisons are
      used to qualitatively assess the degree of fidelity of the bulk scattering
      approximations provided by both functions.

PMID- 19104611
TI  - Luminescent Solar Concentrators--a review of recent results.
AB  - Luminescent solar concentrators (LSCs) generally consist of transparent polymer
      sheets doped with luminescent species. Incident sunlight is absorbed by the
      luminescent species and emitted with high quantum efficiency, such that emitted
      light is trapped in the sheet and travels to the edges where it can be collected
      by solar cells. LSCs offer potentially lower cost per Wp. This paper reviews
      results mainly obtained within the framework of the Full-spectrum project. Two
      modeling approaches are presented, i.e., a thermodynamic and a ray-trace one, as
      well as experimental results, with a focus on LSC stability.

PMID- 19104612
TI  - Plasmonic solar cells.
AB  - The scattering from metal nanoparticles near their localized plasmon resonance is
      a promising way of increasing the light absorption in thin-film solar cells.
      Enhancements in photocurrent have been observed for a wide range of
      semiconductors and solar cell configurations. We review experimental and
      theoretical progress that has been made in recent years, describe the basic
      mechanisms at work, and provide an outlook on future prospects in this area.

PMID- 19104613
TI  - Optical waveguide enhanced photovoltaics.
AB  - Enhanced light to electric power conversion efficiency of photovoltaic cells with
      a low absorbance was achieved using waveguide integration. We present a proof of
      concept using a very thin dye-sensitized solar cell which absorbed only a small
      fraction of the light at normal incidence. The glass substrate in conjunction
      with the solar cells reflecting back contact formed a planar waveguide, which
      lead to more than four times higher conversion efficiency compared to
      conventional illumination at normal incidence. This illumination concept leads to
      a new type of multi-junction PV systems based on enforced spectral splitting
      along the waveguide.

PMID- 19104614
TI  - Optical properties of microalgae for enhanced biofuels production.
AB  - Research seeks to alter the optical characteristics of microalgae in order to
      improve solar-to-biofuels energy conversion efficiency in mass culture under
      bright sunlight conditions. This objective is achieved by genetically truncating
      the size of the light-harvesting chlorophyll arrays that serve to absorb sunlight
      in the photosynthetic apparatus.

PMID- 19104615
TI  - Optically powered fiber networks.
AB  - Optically powered networks are demonstrated. Heterogeneous subscribers having
      widely varying needs with respect to power and band-width can be effectively
      controlled and optically supplied by a central of-fice. The success of the scheme
      relies both on power-efficient innovative hardware and on a novel low-energy
      medium access control protocol. We demonstrate a sensor network with subscribers
      consuming less than 1 microW average power, and an optically powered high-speed
      video link transmitting data at a bitrate of 100 Mbit/s.

PMID- 19104616
TI  - Transcending the replacement paradigm of solid-state lighting.
AB  - The field of photonics starts with the efficient generation of light. The
      generation of efficient yet highly controllable light can indeed be accomplished
      with light-emitting diodes (LEDs), which are, in principle, capable of generating
      white light with a 20 times greater efficiency than conventional light bulbs.
      Deployed on a global scale to replace conventional sources, such solid-state
      light sources will result in enormous benefits that, over a period of 10 years,
      include (1) gigantic energy savings of 1.9 x 1020 joule, (2) a very substantial
      reduction in global-warming CO2 emissions, (3) a strong reduction in the emission
      of pollutants such as acid-rain-causing SO2, mercury (Hg), and uranium (U), and
      (4) financial savings exceeding a trillion (10(12)) US$. These benefits can be
      accomplished by the "replacement paradigm" in which conventional light sources
      are replaced by more energy efficient, more durable, and non-toxic light sources.
      However, it will be shown that solid-state light sources can go beyond the
      replacement paradigm, by providing new capabilities including the control of
      spectrum, color temperature, polarization, temporal modulation, and spatial
      emission pattern. We will show that such future, "smart" light sources, can
      harness the huge potential of LEDs by offering multi-dimensional controllability
      that will enhance the functionality and performance of light sources in a wide
      range of applications. These applications include optical microscopy, imaging,
      display technologies, communications, networking, and transportation systems.

PMID- 19104617
TI  - Real-time extended depth of field microscopy.
AB  - We describe an optical microscope system whose focal setting can be changed
      quickly without moving the objective lens or specimen. Using this system,
      diffraction limited images can be acquired from a wide range of focal settings
      without introducing optical aberrations that degrade image quality. We combine
      this system with a real time Nipkow disc based confocal microscope so as to
      permit the acquisition of extended depth of field images directly in a single
      frame of the CCD camera. We also demonstrate a simple modification that enables
      extended depth of field images to be acquired from different angles of
      perspective, where the angle can be changed over a continuous range by the user
      in real-time.

PMID- 19104618
TI  - Multiple-input single-output FIFO optical buffers with controllable fractional
      delay lines.
AB  - Optical buffering is a major challenge in realizing all-optical packet switching.
      In this paper we propose a new buffer called a multipleinput single-output FIFO
      (MISO-FIFO) optical buffer that supports several functions normally associated
      with electronic RAM. Our structure reduces the physical size of a buffer by up to
      an order of magnitude or more by allowing reuse of its basic optical delay line
      (ODL) elements. Moreover, by using controllable fractional delay lines (CFDLs) as
      the basic building block we are able to reduce t size and frequency of voids in
      the output of the buffer. We develop a Markov Chain (MC) model for the
      performance of our new buffering scheme, and demonstrate the advantages of our
      structure over buffer structures that use ODLs in terms of throughput and link
      utilization.

PMID- 19104619
TI  - The use of a negative index planoconcave lens array for wide-viewing angle
      integral imaging.
AB  - Wide-viewing angle integral imaging by means of a negative refractive index
      planoconcave lens array is theoretically investigated. The optical properties of
      a negative refractive index lens are analyzed from the point of view of integral
      imaging. The effective focal length of a positive index planoconvex lens and a
      negative index planoconcave lens with the same surface spherical curvature R are
      approximated as fP,eff = 2R and fN,eff = 0.4 R, respectively. This short
      effective focal length of the negative index lens is advantageous for extending
      the viewing angle of the integral imaging. In addition, some other optical
      properties of a negative index lens are analyzed and compared for a positive
      index lens. Three-dimensional ray-tracing observation simulations of integral
      imaging systems with a negative index lens array and a positive index lens array
      are then performed, in a comparative study of the wide- ewing angle mode for
      integral imaging. A three-dimensional ray-tracing simulator for an integral
      imaging system is then developed. Some interesting issues that appear in the wide
      viewing mode of integral imaging are discussed. The negative refractive index
      planoconcave lens was found to give a wider viewing angle of -60(deg.)
      approximately +60(deg.) and reduces aberration with only a single spherical
      planoconcave lens.

PMID- 19104620
TI  - 2.6 W optically-pumped semiconductor disk laser operating at 1.57-microm using
      wafer fusion.
AB  - We report a wafer fused high power optically pumped semiconductor disk laser
      incorporating InP-based active medium fused to a GaAs/AlGaAs distributed Bragg
      reflector. A record value of over 2.6 W of output power in a spectral range
      around 1.57 microm was demonstrated, revealing the essential advantage of the
      wafer fusing technique over monolithically-grown all-InP-based structures. The
      presented approach allows for integration of lattice-mismatched compounds,
      quantum-well and quantum-dot based media. This would provide convenient means for
      extending the wavelength range of semiconductor disk lasers.

PMID- 19104621
TI  - A three-dimensional radiative transfer model for shallow water environments.
AB  - A geometric optical model for three-dimensional radiative transfer capable of
      handling arbitrary arrangements of surfaces within anisotropic scattering media
      is described. The model operates by discretizing surfaces and volumes into
      patches and voxels and establishing the radiative transfer relationship between
      every pair of elements. In a plane-parallel configuration results for directional
      radiance agree closely with the numerical integration invariant imbedded method.
      Model accuracy for two examples incorporating surface water waves and complex
      benthic structures were assessed by conservation of energy, errors were less than
      1%. Potential applications in remote sensing or photobiological studies of
      structurally complex benthos in shallow water environments are illustrated.

PMID- 19104622
TI  - Rigorous solution for the transient Surface Plasmon Polariton launched by
      subwavelength slit scattering.
AB  - We demonstrate by a rigorous theoretical calculation the transient Surface
      Plasmon Polariton (SPP) mode, which is launched by a beam impinging onto a sub
      wavelength real metallic slit in addition to the conventional long-range SPP.
      Different from the previous works, we find a direct closed-form solution of the
      Maxwell's equations by the Sommerfeld branch-cut integrals without approximation.
      The transient wave is a SPP with a complex-valued envelope, expressed as the
      exponential integral. Its rapid damping may be asymptotically approximated as -
      ln(x), 1/ x1/2 and 1/x, respectively, depending on the distance range away from
      the slit. The transit SPP may be considered as a cylindrical wave, which is
      radiated from the slit, takes the SPP propagation constant at the interface and
      propagates with additional drop due to the loss of energy pumped to the SPP.

PMID- 19104623
TI  - Large enhancement of femtosecond laser micromachining speed in dye-doped hydrogel
      polymers.
AB  - Ophthalmologic hydrogel polymers are doped with Fluorescein or Coumarin dyes
      prior to the femtosecond laser micromachining process. We find that the
      achievable micromachining writing speed can be greatly increased while
      maintaining large refractive index changes (up to +0.08). Compared with previous
      results in dye-doped polymers that do not contain water such as PMMA, we obtain
      much larger index changes and much faster writing speeds.

PMID- 19104624
TI  - Two-photon resonant excitation of a doubly excited state in He atoms by high
      harmonic pulses.
AB  - We experimentally demonstrate a two-color two-photon resonant excitation of the
      doubly excited 2p2 1S state in helium atoms by the combination of 19th and 21st
      harmonic photons of a Ti:sapphire laser. Production of the 2p2 1S state is
      confirmed by the experimental observation that the electron emission from this
      state does not depend on the direction of harmonic polarization. Our ab-initio
      theoretical results through the solution of time-dependent Schrodinger equation
      are consistent with the experimental results and confirm the first successful
      production of a doubly excited state by high-harmonic pulses.

PMID- 19104625
TI  - 100 GHz passively mode-locked Er:Yb:glass laser at 1.5 microm with 1.6-ps pulses.
AB  - We demonstrate a compact diode-pumped fundamentally modelocked Er:Yb:glass laser
      with a record high repetition rate of 101 GHz, generating 35 mW average power in
      1.6-ps pulses in the 1.5-microm telecom window. This performance makes the laser
      an attractive pulse generator to be used in advanced high-speed return-to-zero
      (RZ) telecom systems.

PMID- 19104626
TI  - Ultra-low repetition rate mode-locked fiber laser with high-energy pulses.
AB  - This paper reports on the results of research into passively modelocked fiber
      laser with a record-setting optical length of the resonant cavity amounting to
      3.8 km. Significant elongation of the laser resonator led to more than two orders
      of magnitude increase in the output pulse energy at the same pump radiation
      power. At ultra-low (for mode-locked lasers) pulse repetition rate (77 kHz) and
      pulse duration of 3 ns the energy per pulse reached 3.9 microJ. At this moment
      this is the highest pulse energy on record generated directly from a mode-locked
      laser without Q-switching, cavity dumping techniques, or additional optical
      amplifiers.

PMID- 19104629
TI  - Intra-symbol frequency-domain averaging based channel estimation for coherent
      optical OFDM.
AB  - We present an efficient channel estimation method for coherent optical OFDM (CO
      OFDM) based on intra-symbol frequency-domain averaging (ISFA), and systematically
      study its robustness against transmission impairments such as optical noise,
      chromatic dispersion (CD), polarization-mode dispersion (PMD), polarization
      dependent loss (PDL), and fiber nonlinearity. Numerical simulations are performed
      for a 112-Gb/s polarization-division multiplexed (PDM) CO-OFDM signal, and the
      ISFAbased channel estimation and the subsequent channel compensation are found to
      be highly robust against these transmission impairments in typical optical
      transport systems.

PMID- 19104630
TI  - High efficiency, multi-Watt CW yellow emission from an intracavity-doubled self
      Raman laser using Nd:GdVO4.
AB  - Efficient multi-Watt continuous-wave (CW) yellow emission at 586.5 nm is
      demonstrated through intracavity frequency-doubling of a Nd:GdVO(4) self-Raman
      laser pumped at 880 nm. 2.51 W of CW yellow emission with an overall diode-to
      yellow conversion efficiency of 12.2% is achieved through the use of a 20 mm long
      Nd:GdVO(4) self-Raman crystal and an intracavity mirror which facilitates
      collection of yellow emission generated within the resonator, and reduces thermal
      loading of the laser crystal.

PMID- 19104631
TI  - DPSK multicast using multiple-pump FWM in Bismuths highly nonlinear fiber with
      high multicast efficiency.
AB  - In this paper, we discuss the multicast efficiency issue in the optical layer
      multicast. A 1-to-8 phase-preserved different phase-shifted keying (DPSK)
      wavelength multicast is experimentally demonstrated using four-wave mixing (FWM)
      in a piece of Bismuth highly nonlinear fiber (Bi- HNLF). DPSK signal is
      successfully delivered from one wavelength to up to eight different wavelengths
      using only three pumps. Compared with the existing schemes, the multicast
      efficiency is greatly improved by delivering the phase information to more
      destination wavelengths.

PMID- 19104632
TI  - Digital reconstruction based on angular spectrum diffraction with the ridge of
      wavelet transform in holographic phase-contrast microscopy.
AB  - A numerical reconstruction technique of digital holography based on angular
      spectrum diffraction by means of the ridge of Gabor wavelet transform (GWT) is
      presented. Appling the GWT, the object wave can be reconstructed by calculating
      the wavelet coefficients of the hologram at the ridge of the GWT automatically
      even if the spectrum of the virtual image is disturbed by the other spectrum. It
      provides a way to eliminate the effect of the zero-order and the twin-image terms
      without the spatial filtering. In particular, based on the angular spectrum
      theory, GWT is applied to the digital holographic phase-contrast microscopy on
      biological specimens. The theory, the results of a simulation and an experiment
      of an onion specimen are shown.

PMID- 19104633
TI  - Generation of super-resolution atomic state density distribution based on
      temporally-cascaded multiple light exposures.
AB  - We propose a novel approach to optical generation of superresolution atomic state
      density distribution based on interaction between Lambda- type atoms and
      temporally-cascaded driving fields. The scheme effectively inscribes
      multiplication of optical intensity profiles on atomic state density
      distribution, which can produce arbitrary patterns beyond the diffraction limit.
      The degree of resolution enhancement can be increased, not depending on the
      intrinsic nonlinearity of the photographic medium or the number of simultaneously
      interacting fields unlike the previous schemes. Procedures for drawing arbitrary
      two-dimensional patterns and effects of atomic state decoherence are described.

PMID- 19104634
TI  - Chromatic dispersion compensation and fiber nonlinearity mitigation of OOK
      signals with diverse-VSB-filtering FFE and DFE.
AB  - We propose a diverse vestigial-sideband-filtering feed forward equalizer and
      decision feedback equalizer (DVSB-FFE-DFE), which is capable of compensating
      residual chromatic dispersion (CD) as well as mitigating fiber nonlinearity in on
      off keying (OOK) systems. In DVSBFFE-DFE, the upper and the lower VSB filtered
      signals are jointly equalized with FFE followed by DFE. Simulation results show
      that in a 42.7 Gbit/s nonreturn-to-zero OOK system, DVSB-FFE-DFE can effectively
      mitigate the required optical signal-to-noise ratio penalty induced by residual
      CD and fiber nonlinearity.

PMID- 19104635
TI  - Controlling intermodal four-wave mixing from the design of microstructured
      optical fibers.
AB  - Intermodal four-wave mixing (FWM) in microstructured optical fibers (MOF) is
      studied theoretically and experimentally. The dependance of FWM frequency
      detuning on the geometrical parameters of the fiber, namely the pitch, the core
      width and the air-filling fraction is derived. We propose to use the results of
      this investigation to control the position of the Stokes and anti-Stokes waves
      directly from the fiber transverse structure drawing without the need for time
      consuming simulations as in usual design procedures. Stokes sideband can then be
      freely tuned within the S-, L-, and C- bands with great potential for infrared
      applications.

PMID- 19104636
TI  - Optical resonances on sub-wavelength silver lamellar gratings.
AB  - The optical response of sub-wavelength silver lamellar gratings has been
      theoretically investigated. Two distinct types of resonance have been predicted
      for incident radiation with E-field perpendicular to the long axis of the wires.
      The first resonance has been identified as a cavity mode resonance that is
      associated with transmission enhancement. The second resonance has been
      identified as an entirely new horizontal plasmon resonance on the incident (and
      transmission) surfaces of the wires of the grating. Normal surface plasmon modes
      are investigated on discontinuous gratings, and their relation to those found on
      continuous gratings is highlighted by focusing on the perturbation effect of the
      discontinuities. It is shown that the new horizontal plasmon mode is in no way
      related to the well known diffractively coupled surface plasmon, and is shown to
      have a particle plasmon-like nature. It is therefore termed a horizontal particle
      plasmon, and may be either an uncoupled horizontal particle plasmon resonance (a
      1-dimensional particle plasmon) or a coupled horizontal particle plasmon
      resonance (a 2-dimensional particle plasmon) depending on the height of the
      grating. It is shown that this resonance may result in a reflection efficiency
      that is very high, even when the grating would be optically thin if it were a
      homogeneous film, therefore, it behaves as an inverse wire grid polariser as it
      reflects more TM than TE incident radiation.

PMID- 19104637
TI  - Channeling light along a chain of near-field coupled gold nanoparticles near a
      metallic film.
AB  - We study the propagation of light along a chain of 20-nm-spaced gold particles
      lying onto a silica substrate in which a metallic film can be incorporated. We
      first discuss, for a pure dielectric substrate, the specificities of the chain
      modes as compared to larger separation distances where far-field coupling
      dominates. We then show how the introduction of a buried metallic film allows a
      substantial increase in the propagation lengths. Finally, we discuss the
      crosstalk between two adjacent chains, with and without the buried metallic
      layer, for applications to ultra-compact interconnects.

PMID- 19104638
TI  - Patterned two-photon illumination by spatiotemporal shaping of ultrashort pulses.
AB  - Multiphoton excitation by temporally focused pulses can be combined with spatial
      Fourier-transform pulse shaping techniques to enhance spatial control of the
      excitation volume. Here we propose and demonstrate an optical system for the
      generation of such spatiotemporally engineered light pulses using a combination
      of spatial control by a two-dimensional reconfigurable light modulator, with a
      dispersive optical setup for temporal focusing. We show that although the
      properties of a holographic beam significantly differ from those of plane-wave
      illumination used in previous temporal focusing realizations, this leads only to
      a slightly reduced axial resolution. We show that the system can provide
      scanningless, arbitrarily shaped, depth resolved excitation patterns that offer
      new perspectives for multiphoton photoactivation and optical lithography
      applications.

PMID- 19104639
TI  - Three dimensional tracking of fluorescent microparticles using a photon-limited
      double-helix response system.
AB  - We demonstrate three-dimensional tracking of fluorescent microparticles, with a
      computational optical system whose point spread function (PSF) has been
      engineered to have two twisting lobes along the optical axis, generating a three
      dimensional (3D) double-helix (DH) PSF. An information theoretical comparison in
      photon limited systems shows that the DH-PSF delivers higher Fisher information
      for 3D localization than the standard PSF. Hence, DH-PSF systems provide better
      position estimation accuracy. Experiments demonstrate average position estimation
      accuracies under 14nm and 37nm in the transverse and axial dimensions
      respectively. The system determines the 3D position of multiple particles with a
      single image and tracks them over time while providing their velocities.

PMID- 19104640
TI  - Passively Q-switched Tm3+, Ho3+-doped silica fiber laser using a highly nonlinear
      saturable absorber and dynamic gain pulse compression.
AB  - We demonstrate a compact core-pumped 2 microm Tm(3+), Ho(3+)- doped all-fiber
      laser passively Q-switched with an antimony-based saturable absorber. The 20 ns
      pulses are the shortest Q-switched pulses from a fiber laser operating beyond
      1850 nm and were produced at a repetition rate of 57 kHz and pulse energy of 15
      microJ using a short-length (4 ns) cavity. The large absorber modulation depth of
      approximately 70% together with transient gain compression is shown to provide an
      efficient mechanism for Q-switched pulse shortening.

PMID- 19104641
TI  - Ytterbium-doped fibre laser Q-switched by a cantilever-type micro-mirror.
AB  - We present an Ytterbium fibre laser operating in the Q-switch regime by using a
      Micro- Opto- Electro- Mechanical System (MOEMS) of novel design. The cantilever
      type micro-mirror is designed to generate short laser pulses with duration
      between 20 ns and 100 ns at repetition rates ranging from a few kilohertz up to
      800 kHz. The bent profile of this new type of MOEMS ensures a high modulation
      rate of the laser cavity losses while keeping a high actuating frequency.

PMID- 19104642
TI  - General method for designing wave shape transformers.
AB  - An effective method for designing wave shape transformers (WSTs) is investigated
      by adopting the coordinate transformation theory. Following this method, the
      devices employed to transform electromagnetic (EM) wave fronts from one style
      with arbitrary shape and size to another style, can be designed. To verify this
      method, three examples in 2D spaces are also presented. Compared with the methods
      proposed in other literatures, this method offers the general procedure in
      designing WSTs, and thus is of great importance for the potential and practical
      applications possessed by such kinds of devices.

PMID- 19104643
TI  - Interference terahertz label-free imaging for protein detection on a membrane.
AB  - We demonstrate a highly sensitive imaging method combined a terahertz time-domain
      spectroscopy and an interference effect for label-free protein detection on a
      polyvinylidene difluoride membrane. The method is based on terahertz time-domain
      spectroscopy and uses an interference effect. Biotin is linked to the membrane
      using poly ethylene glycol or poly ethylene glycol methyl ether to prevent it
      from being washed off. Binding of the biotin with streptavidin is then observed
      by measuring the terahertz signal change due to the variation of the membrane
      refractive index. We demonstrate the detection of the binding streptavidin
      protein in gradually decreasing concentrations, down to 27 ng mm-2, using the
      image recorded at 1.5 THz.

PMID- 19104644
TI  - Controlling the carrier-envelope phase of few-cycle focused laser beams with a
      dispersive beam expander.
AB  - We report on a procedure to focalize few-cycle laser pulses in dispersive media
      with controlled waveform. Stationarity of the carrier-envelope phase for extended
      depth of focus is attained by shaping the spatial dispersion of the ultrashort
      beam. An adjustable group velocity is locally tuned in order to match a
      prescribed phase velocity at focus. A hybrid diffractive-refractive lens system
      is proposed to drive the wavefield to an immersion microscope objective under
      convenient broadband modulation. Numerical simulations demonstrate robustness
      over positioning of this dispersive beam expander.

PMID- 19104645
TI  - Wavelength-multiplexed distribution of highly entangled photon-pairs over optical
      fiber.
AB  - We report the first experimental demonstration of wavelength-multiplexed
      entanglement distribution over optical fiber. Forty-four channels of polarization
      entangled photon-pairs were produced from a single pulse-pumped, short
      periodically-poled lithium niobate waveguide and distributed over 10 km of
      dispersion-shifted optical fiber. Entanglement fidelities of the distributed
      photon-pairs exceeded 0.86 for all selected channels.

PMID- 19104646
TI  - Strong anomalous optical dispersion of graphene: complex refractive index
      measured by Picometrology.
AB  - We introduce spinning-disc Picometrology which is designed to measure complex
      refractive index of ultra-thin and size-limited sample deposited on a solid
      surface. Picometrology is applied to measure the refractive index of graphene on
      thermal oxide on silicon. The refractive index varies from ng = 2.4-1.0i at 532
      nm to ng = 3.0-1.4i at 633 nm at room temperature. The dispersion is five times
      stronger than bulk graphite (2.67- 1.34i to 2.73-1.42i from 532 nm to 633 nm).

PMID- 19104647
TI  - Fiber cross-sectional imaging by manually controlled low coherence light sources.
AB  - We couple a variable-coherence light beam into a multimode optical fiber and
      observe the fiber cross-sectional images. The variation in the fiber imaging is
      explored as we change the degree of optical coherence of the incident light. Low
      coherence light is shown to be capable of improving the quality of the fiber
      images. Various mode patterns of a multimode optical fiber are also shown
      numerically and experimentally to elucidate the fiber coupling characteristics.

PMID- 19104648
TI  - Cascaded four-wave mixing and multicolored arrays generation in a sapphire plate
      by using two crossing beams of femtosecond laser.
AB  - Ultrabroadband signals were found to be generated by cascaded four-wave mixing in
      a bulk medium by using two crossing femtosecond laser pulses. As many as fifteen
      spectral upshifted pulses and two spectral downshifted pulses were obtained with
      spectral bandwidth broader than 1.5 octaves. Bright upshifted pulses were
      observed on both sides of the two crossing beams. Two dimensional multicolored
      arrays were observed for the first time in a sapphire plate medium.

PMID- 19104649
TI  - Nonlinear optics: the next decade.
AB  - This paper concludes the Focus Serial assembled of invited papers in key areas of
      nonlinear optics (Editors: J.M. Dudley and R.W. Boyd), and it discusses new
      directions for future research in this field.

PMID- 19104650
TI  - Leishmania-induced IRAK-1 inactivation is mediated by SHP-1 interacting with an
      evolutionarily conserved KTIM motif.
AB  - Parasites of the Leishmania genus can rapidly alter several macrophage (MO)
      signalling pathways in order to tame down the innate immune response and
      inflammation, therefore favouring their survival and propagation within their
      mammalian host. Having recently reported that Leishmania and bacterial LPS
      generate a significantly stronger inflammatory response in animals and phagocytes
      functionally deficient for the Src homology 2 domain-containing protein tyrosine
      phosphatase (SHP-1), we hypothesized that Leishmania could exploit SHP-1 to
      inactivate key kinases involved in Toll-like receptor (TLR) signalling and innate
      immunity such as IL-1 receptor-associated kinase 1 (IRAK-1). Here we show that
      upon infection, SHP-1 rapidly binds to IRAK-1, completely inactivating its
      intrinsic kinase activity and any further LPS-mediated activation as well as MO
      functions. We also demonstrate that the SHP-1/IRAK-1 interaction occurs via an
      evolutionarily conserved ITIM-like motif found in the kinase domain of IRAK-1,
      which we named KTIM (Kinase Tyrosyl-based Inhibitory Motif). This regulatory
      motif appeared in early vertebrates and is not found in any other IRAK family
      member. Our study additionally reveals that several other kinases (e.g. Erk1/2,
      IKKalpha/beta) involved in downstream TLR signalling also bear KTIMs in their
      kinase domains and interact with SHP-1. We thus provide the first demonstration
      that a pathogen can exploit a host protein tyrosine phosphatase, namely SHP-1, to
      directly inactivate IRAK-1 through a generally conserved KTIM motif.

PMID- 19104651
TI  - Development and validation of a severity scale for leprosy type 1 reactions.
AB  - OBJECTIVES: To develop a valid and reliable quantitative measure of leprosy Type
      1 reactions. METHODS: A scale was developed from previous scales which had not
      been validated. The face and content validity were assessed following
      consultation with recognised experts in the field. The construct validity was
      determined by applying the scale to patients in Bangladesh and Brazil who had
      been diagnosed with leprosy Type 1 reaction. An expert categorized each patient's
      reaction as mild or moderate or severe. Another worker applied the scale. This
      was done independently. In a subsequent stage of the study the agreement between
      two observers was assessed. RESULTS: The scale had good internal consistency
      demonstrated by a Cronbach's alpha >0.8. Removal of three items from the original
      scale resulted in better discrimination between disease severity categories. Cut
      off points for Type 1 reaction severities were determined using Receiver
      Operating Characteristic curves. A mild Type 1 reaction is characterized using
      the final scale by a score of 4 or less. A moderate reaction is a score of
      between 4.5 and 8.5. A severe reaction is a score of 9 or more. CONCLUSIONS: We
      have developed a valid and reliable tool for quantifying leprosy Type 1 reaction
      severity and believe this will be a useful tool in research of this condition, in
      observational and intervention studies, and in the comparison of clinical and
      laboratory parameters.

PMID- 19104652
TI  - Differential gene repertoire in Mycobacterium ulcerans identifies candidate genes
      for patho-adaptation.
AB  - BACKGROUND: Based on large genomic sequence polymorphisms, several haplotypes
      belonging to two major lineages of the human pathogen Mycobacterium ulcerans
      could be distinguished among patient isolates from various geographic origins.
      However, the biological relevance of insertional/deletional diversity is not
      understood. METHODOLOGY: Using comparative genomics, we have investigated the
      genes located in regions of difference recently identified by DNA microarray
      based hybridisation analysis. The analysed regions of difference comprise
      approximately 7% of the entire M. ulcerans genome. PRINCIPAL FINDINGS: Several
      different mechanisms leading to loss of functional genes were identified, ranging
      from pseudogenization, caused by frame shift mutations or mobile genetic element
      interspersing, to large sequence polymorphisms. Four hot spot regions for genetic
      instability were unveiled. Altogether, 229 coding sequences were found to be
      differentially inactivated, constituting a repertoire of coding sequence
      variation in the rather monomorphic M. ulcerans. CONCLUSIONS/SIGNIFICANCE: The
      differential gene inactivation patterns associated with the M. ulcerans
      haplotypes identified candidate genes that may confer enhanced adaptation upon
      ablation of expression. A number of gene conversions confined to the classical
      lineage may contribute to particular virulence of this group comprising isolates
      from Africa and Australia. Identification of this spectrum of anti-virulence gene
      candidates expands our understanding of the pathogenicity and ecology of the
      emerging infectious disease Buruli ulcer.

PMID- 19104653
TI  - The burden of human African trypanosomiasis.
AB  - Human African trypanosomiasis (HAT, or sleeping sickness) is a protozoan
      parasitic infection caused by Trypanosoma brucei rhodesiense or Trypanosoma
      brucei gambiense. These are neglected tropical diseases, and T.b. rhodesiense HAT
      is a zoonosis. We review current knowledge on the burden of HAT in sub-Saharan
      Africa, with an emphasis on the disability-adjusted life year (DALY), data
      sources, and methodological issues relating to the use of this metric for
      assessing the burden of this disease. We highlight areas where data are lacking
      to properly quantify the impact of these diseases, mainly relating to quantifying
      under-reporting and disability associated with infection, and challenge the HAT
      research community to tackle the neglect in data gathering to enable better
      evidence-based assessments of burden using DALYs or other appropriate measures.

PMID- 19104654
TI  - TranscriptomeBrowser: a powerful and flexible toolbox to explore productively the
      transcriptional landscape of the Gene Expression Omnibus database.
AB  - BACKGROUND: As public microarray repositories are constantly growing, we are
      facing the challenge of designing strategies to provide productive access to the
      available data. METHODOLOGY: We used a modified version of the Markov clustering
      algorithm to systematically extract clusters of co-regulated genes from hundreds
      of microarray datasets stored in the Gene Expression Omnibus database (n =
      1,484). This approach led to the definition of 18,250 transcriptional signatures
      (TS) that were tested for functional enrichment using the DAVID knowledgebase.
      Over-representation of functional terms was found in a large proportion of these
      TS (84%). We developed a JAVA application, TBrowser that comes with an open plug
      in architecture and whose interface implements a highly sophisticated search
      engine supporting several Boolean operators (http://tagc.univ-mrs.fr/tbrowser/).
      User can search and analyze TS containing a list of identifiers (gene symbols or
      AffyIDs) or associated with a set of functional terms. CONCLUSIONS/SIGNIFICANCE:
      As proof of principle, TBrowser was used to define breast cancer cell specific
      genes and to detect chromosomal abnormalities in tumors. Finally, taking
      advantage of our large collection of transcriptional signatures, we constructed a
      comprehensive map that summarizes gene-gene co-regulations observed through all
      the experiments performed on HGU133A Affymetrix platform. We provide evidences
      that this map can extend our knowledge of cellular signaling pathways.

PMID- 19104655
TI  - Fine-scale phylogeographic structure of Borrelia lusitaniae revealed by
      multilocus sequence typing.
AB  - Borrelia lusitaniae is an Old World species of the Lyme borreliosis (LB) group of
      tick-borne spirochetes and prevails mainly in countries around the Mediterranean
      Basin. Lizards of the family Lacertidae have been identified as reservoir hosts
      of B. lusitaniae. These reptiles are highly structured geographically, indicating
      limited migration. In order to examine whether host geographic structure shapes
      the evolution and epidemiology of B. lusitaniae, we analyzed the phylogeographic
      population structure of this tick-borne bacterium using a recently developed
      multilocus sequence typing (MLST) scheme based on chromosomal housekeeping genes.
      A total of 2,099 questing nymphal and adult Ixodes ricinus ticks were collected
      in two climatically different regions of Portugal, being approximately 130 km
      apart. All ticks were screened for spirochetes by direct PCR. Attempts to isolate
      strains yielded 16 cultures of B. lusitaniae in total. Uncontaminated cultures as
      well as infected ticks were included in this study. The results using MLST show
      that the regional B. lusitaniae populations constitute genetically distinct
      populations. In contrast, no clear phylogeographic signals were detected in
      sequences of the commonly used molecular markers ospA and ospC. The pronounced
      population structure of B. lusitaniae over a short geographic distance as
      captured by MLST of the housekeeping genes suggests that the migration rates of
      B. lusitaniae are rather low, most likely because the distribution of
      mediterranean lizard populations is highly parapatric. The study underlines the
      importance of vertebrate hosts in the geographic spread of tick-borne
      microparasites.

PMID- 19104656
TI  - The natural progression of Gambiense sleeping sickness: what is the evidence?
AB  - Gambiense human African trypanosomiasis (HAT, sleeping sickness) is widely
      assumed to be 100% pathogenic and fatal. However, reports to the contrary exist,
      and human trypano-tolerance has been postulated. Furthermore, there is
      uncertainty about the actual duration of both stage 1 and stage 2 infection,
      particularly with respect to how long a patient remains infectious. Understanding
      such basic parameters of HAT infection is essential for optimising control
      strategies based on case detection. We considered the potential existence and
      relevance of human trypano-tolerance, and explored the duration of
      infectiousness, through a review of published evidence on the natural progression
      of gambiense HAT in the absence of treatment, and biological considerations.
      Published reports indicate that most gambiense HAT cases are fatal if untreated.
      Self-resolving and asymptomatic chronic infections probably constitute a minority
      if they do indeed exist. Chronic carriage, however, deserves further study, as it
      could seed renewed epidemics after control programmes cease.

PMID- 19104657
TI  - Strong association of a common dihydropyrimidine dehydrogenase gene polymorphism
      with fluoropyrimidine-related toxicity in cancer patients.
AB  - BACKGROUND: Cancer patients carrying mutations in the dihydropyrimidine
      dehydrogenase gene (DPYD) have a high risk to experience severe drug-adverse
      effects following chemotherapy with fluoropyrimidine drugs such as 5-fluorouracil
      (5-FU) or capecitabine. The pretreatment detection of this impairment of
      pyrimidine catabolism could prevent serious, potentially lethal side effects. As
      known deleterious mutations explain only a limited proportion of the drug-adverse
      events, we systematically searched for additional DPYD variations associated with
      enhanced drug toxicity. METHODOLOGY/PRINCIPAL FINDINGS: We performed a whole gene
      approach covering the entire coding region and compared DPYD genotype frequencies
      between cancer patients with good (n = 89) and with poor (n = 39) tolerance of a
      fluoropyrimidine-based chemotherapy regimen. Applying logistic regression
      analysis and sliding window approaches we identified the strongest association
      with fluoropyrimidine-related grade III and IV toxicity for the non-synonymous
      polymorphism c.496A>G (p.Met166Val). We then confirmed our initial results using
      an independent sample of 53 individuals suffering from drug-adverse-effects. The
      combined odds ratio calculated for 92 toxicity cases was 4.42 [95% CI 2.12-9.23];
      p (trend)<0.001; p (corrected) = 0.001; the attributable risk was 56.9%.
      Comparing tumor-type matched sets of samples, correlation of c.496A>G with
      toxicity was particularly present in patients with gastroesophageal and breast
      cancer, but did not reach significance in patients with colorectal malignancies.
      CONCLUSION: Our results show compelling evidence that, at least in distinct tumor
      types, a common DPYD polymorphism strongly contributes to the occurrence of
      fluoropyrimidine-related drug adverse effects. Carriers of this variant could
      benefit from individual dose adjustment of the fluoropyrimidine drug or alternate
      therapies.

PMID- 19104658
TI  - Human helminth co-infection: analysis of spatial patterns and risk factors in a
      Brazilian community.
AB  - BACKGROUND: Individuals living in areas endemic for helminths are commonly
      infected with multiple species. Despite increasing emphasis given to the
      potential health impacts of polyparasitism, few studies have investigated the
      relative importance of household and environmental factors on the risk of
      helminth co-infection. Here, we present an investigation of exposure-related risk
      factors as sources of heterogeneity in the distribution of co-infection with
      Necator americanus and Schistosoma mansoni in a region of southeastern Brazil.
      METHODOLOGY: Cross-sectional parasitological and socio-economic data from a
      community-based household survey were combined with remotely sensed environmental
      data using a geographical information system. Geo-statistical methods were used
      to explore patterns of mono- and co-infection with N. americanus and S. mansoni
      in the region. Bayesian hierarchical models were then developed to identify risk
      factors for mono- and co-infection in relation to community-based survey data to
      assess their roles in explaining observed heterogeneity in mono and co-infection
      with these two helminth species. PRINCIPAL FINDINGS: The majority of individuals
      had N. americanus (71.1%) and/or S. mansoni (50.3%) infection; 41.0% of
      individuals were co-infected with both helminths. Prevalence of co-infection with
      these two species varied substantially across the study area, and there was
      strong evidence of household clustering. Hierarchical multinomial models
      demonstrated that relative socio-economic status, household crowding, living in
      the eastern watershed and high Normalized Difference Vegetation Index (NDVI) were
      significantly associated with N. americanus and S. mansoni co-infection. These
      risk factors could, however, only account for an estimated 32% of variability
      between households. CONCLUSIONS: Our results demonstrate that variability in risk
      of N. americanus and S. mansoni co-infection between households cannot be
      entirely explained by exposure-related risk factors, emphasizing the possible
      role of other household factors in the heterogeneous distribution of helminth co
      infection. Untangling the relative contribution of intrinsic host factors from
      household and environmental determinants therefore remains critical to our
      understanding of helminth epidemiology.

PMID- 19104659
TI  - A small community model for the transmission of infectious diseases: comparison
      of school closure as an intervention in individual-based models of an influenza
      pandemic.
AB  - BACKGROUND: In the absence of other evidence, modelling has been used extensively
      to help policy makers plan for a potential future influenza pandemic. METHOD: We
      have constructed an individual based model of a small community in the developed
      world with detail down to exact household structure obtained from census
      collection datasets and precise simulation of household demographics, movement
      within the community and individual contact patterns. We modelled the spread of
      pandemic influenza in this community and the effect on daily and final attack
      rates of four social distancing measures: school closure, increased case
      isolation, workplace non-attendance and community contact reduction. We compared
      the modelled results of final attack rates in the absence of any interventions
      and the effect of school closure as a single intervention with other published
      individual based models of pandemic influenza in the developed world. RESULTS: We
      showed that published individual based models estimate similar final attack rates
      over a range of values for R(0) in a pandemic where no interventions have been
      implemented; that multiple social distancing measures applied early and
      continuously can be very effective in interrupting transmission of the pandemic
      virus for R(0) values up to 2.5; and that different conclusions reached on the
      simulated benefit of school closure in published models appear to result from
      differences in assumptions about the timing and duration of school closure and
      flow-on effects on other social contacts resulting from school closure.
      CONCLUSION: Models of the spread and control of pandemic influenza have the
      potential to assist policy makers with decisions about which control strategies
      to adopt. However, attention needs to be given by policy makers to the
      assumptions underpinning both the models and the control strategies examined.

PMID- 19104660
TI  - A meta-analysis of local adaptation in plants.
AB  - Local adaptation is of fundamental importance in evolutionary, population,
      conservation, and global-change biology. The generality of local adaptation in
      plants and whether and how it is influenced by specific species, population and
      habitat characteristics have, however, not been quantitatively reviewed.
      Therefore, we examined published data on the outcomes of reciprocal transplant
      experiments using two approaches. We conducted a meta-analysis to compare the
      performance of local and foreign plants at all transplant sites. In addition, we
      analysed frequencies of pairs of plant origin to examine whether local plants
      perform better than foreign plants at both compared transplant sites. In both
      approaches, we also examined the effects of population size, and of the habitat
      and species characteristics that are predicted to affect local adaptation. We
      show that, overall, local plants performed significantly better than foreign
      plants at their site of origin: this was found to be the case in 71.0% of the
      studied sites. However, local plants performed better than foreign plants at both
      sites of a pair-wise comparison (strict definition of local adaption) only in
      45.3% of the 1032 compared population pairs. Furthermore, we found local
      adaptation much more common for large plant populations (>1000 flowering
      individuals) than for small populations (<1000 flowering individuals) for which
      local adaptation was very rare. The degree of local adaptation was independent of
      plant life history, spatial or temporal habitat heterogeneity, and geographic
      scale. Our results suggest that local adaptation is less common in plant
      populations than generally assumed. Moreover, our findings reinforce the
      fundamental importance of population size for evolutionary theory. The clear role
      of population size for the ability to evolve local adaptation raises considerable
      doubt on the ability of small plant populations to cope with changing
      environments.

PMID- 19104661
TI  - Clofazimine inhibits human Kv1.3 potassium channel by perturbing calcium
      oscillation in T lymphocytes.
AB  - The Kv1.3 potassium channel plays an essential role in effector memory T cells
      and has been implicated in several important autoimmune diseases including
      multiple sclerosis, psoriasis and type 1 diabetes. A number of potent small
      molecule inhibitors of Kv1.3 channel have been reported, some of which were found
      to be effective in various animal models of autoimmune diseases. We report herein
      the identification of clofazimine, a known anti-mycobacterial drug, as a novel
      inhibitor of human Kv1.3. Clofazimine was initially identified as an inhibitor of
      intracellular T cell receptor-mediated signaling leading to the transcriptional
      activation of human interleukin-2 gene in T cells from a screen of the Johns
      Hopkins Drug Library. A systematic mechanistic deconvolution revealed that
      clofazimine selectively blocked the Kv1.3 channel activity, perturbing the
      oscillation frequency of the calcium-release activated calcium channel, which in
      turn led to the inhibition of the calcineurin-NFAT signaling pathway. These
      effects of clofazimine provide the first line of experimental evidence in support
      of a causal relationship between Kv1.3 and calcium oscillation in human T cells.
      Furthermore, clofazimine was found to be effective in blocking human T cell
      mediated skin graft rejection in an animal model in vivo. Together, these results
      suggest that clofazimine is a promising immunomodulatory drug candidate for
      treating a variety of autoimmune disorders.

PMID- 19104662
TI  - Ethanol/naltrexone interactions at the mu-opioid receptor. CLSM/FCS study in live
      cells.
AB  - BACKGROUND: Alcoholism is a widespread chronic disorder of complex aetiology with
      a significant negative impact on the individual and the society. Mechanisms of
      ethanol action are not sufficiently well understood at the molecular level and
      the pharmacotherapy of alcoholism is still in its infancy. Our study focuses at
      the cellular and molecular level on ethanol-induced effects that are mediated
      through the micro-opioid receptor (MOP) and on the effects of naltrexone, a well
      known antagonist at MOP that is used clinically to prevent relapse in alcoholism.
      METHODOLOGY/PRINCIPAL FINDINGS: Advanced fluorescence imaging by Confocal Laser
      Scanning Microscopy (CLSM) and Fluorescence Correlation Spectroscopy (FCS) are
      used to study ethanol effects on MOP and plasma membrane lipid dynamics in live
      PC12 cells. We observed that relevant concentrations of ethanol (10-40 mM) alter
      MOP mobility and surface density, and affect the dynamics of plasma membrane
      lipids. Compared to the action of specific ligands at MOP, ethanol-induced
      effects show complex kinetics and point to a biphasic underlying mechanism.
      Pretreatment with naloxone or naltrexone considerably mitigates the effects of
      ethanol. CONCLUSIONS/SIGNIFICANCE: We suggest that ethanol acts by affecting the
      sorting of MOP at the plasma membrane of PC12 cells. Naltrexone exerts opposite
      effects on MOP sorting at the plasma membrane, thereby countering the effects of
      ethanol. Our experimental findings give new insight on MOP-mediated ethanol
      action at the cellular and molecular level. We suggest a new hypothesis to
      explain the well established ethanol-induced increase in the activity of the
      endogenous opioid system.

PMID- 19104663
TI  - 3640 unique EST clusters from the medaka testis and their potential use for
      identifying conserved testicular gene expression in fish and mammals.
AB  - BACKGROUND: The fish medaka is the first vertebrate capable of full
      spermatogenesis in vitro from self-renewing spermatogonial stem cells to motile
      test-tube sperm. Precise staging and molecular dissection of this process has
      been hampered by the lack of suitable molecular markers. METHODOLOGY AND
      PRINCIPAL FINDINGS: We have generated a normalized medaka testis cDNA library and
      obtained 7040 high quality sequences representing 3641 unique gene clusters.
      Among these, 1197 unique clusters are homologous to known genes, and 2444 appear
      to be novel genes. Ontology analysis shows that the 1197 gene products are
      implicated in diverse molecular and cellular processes. These genes include
      markers for all major types of testicular somatic and germ cells. Furthermore,
      markers were identified for major spermatogenic stages ranging from
      spermatogonial stem cell self-renewal to meiosis entry, progression and
      completion. Intriguingly, the medaka testis expresses at least 13 homologs of the
      33 mouse X-chromosomal genes that are enriched in the testis. More importantly,
      we show that key components of several signaling pathways known to be important
      for testicular function in mammals are well represented in the medaka testicular
      EST collection. CONCLUSIONS/SIGNIFICANCE: Medaka exhibits a considerable
      similarity in testicular gene expression to mammals. The medaka testicular EST
      collection we obtained has wide range coverage and will not only consolidate our
      knowledge on the comparative analysis of known genes' functions in the testis but
      also provide a rich resource to dissect molecular events and mechanism of
      spermatogenesis in vivo and in vitro in medaka as an excellent vertebrate model.

PMID- 19104664
TI  - Enforced expression of the transcriptional coactivator OBF1 impairs B cell
      differentiation at the earliest stage of development.
AB  - OBF1, also known as Bob.1 or OCA-B, is a B lymphocyte-specific transcription
      factor which coactivates Oct1 and Oct2 on B cell specific promoters. So far, the
      function of OBF1 has been mainly identified in late stage B cell populations. The
      central defect of OBF1 deficient mice is a severely reduced immune response to T
      cell-dependent antigens and a lack of germinal center formation in the spleen.
      Relatively little is known about a potential function of OBF1 in developing B
      cells. Here we have generated transgenic mice overexpressing OBF1 in B cells
      under the control of the immunoglobulin heavy chain promoter and enhancer.
      Surprisingly, these mice have greatly reduced numbers of follicular B cells in
      the periphery and have a compromised immune response. Furthermore, B cell
      differentiation is impaired at an early stage in the bone marrow: a first block
      is observed during B cell commitment and a second differentiation block is seen
      at the large preB2 cell stage. The cells that succeed to escape the block and to
      differentiate into mature B cells have post-translationally downregulated the
      expression of transgene, indicating that expression of OBF1 beyond the normal
      level early in B cell development is deleterious. Transcriptome analysis
      identified genes deregulated in these mice and Id2 and Id3, two known negative
      regulators of B cell differentiation, were found to be upregulated in the EPLM
      and preB cells of the transgenic mice. Furthermore, the Id2 and Id3 promoters
      contain octamer-like sites, to which OBF1 can bind. These results provide
      evidence that tight regulation of OBF1 expression in early B cells is essential
      to allow efficient B lymphocyte differentiation.

PMID- 19104665
TI  - Dendritic spike saturation of endogenous calcium buffer and induction of
      postsynaptic cerebellar LTP.
AB  - The architecture of parallel fiber axons contacting cerebellar Purkinje neurons
      retains spatial information over long distances. Parallel fiber synapses can
      trigger local dendritic calcium spikes, but whether and how this calcium signal
      leads to plastic changes that decode the parallel fiber input organization is
      unknown. By combining voltage and calcium imaging, we show that calcium signals,
      elicited by parallel fiber stimulation and mediated by voltage-gated calcium
      channels, increase non-linearly during high-frequency bursts of electrically
      constant calcium spikes, because they locally and transiently saturate the
      endogenous buffer. We demonstrate that these non-linear calcium signals,
      independently of NMDA or metabotropic glutamate receptor activation, can induce
      parallel fiber long-term potentiation. Two-photon imaging in coronal slices
      revealed that calcium signals inducing long-term potentiation can be observed by
      stimulating either the parallel fiber or the ascending fiber pathway. We propose
      that local dendritic calcium spikes, evoked by synaptic potentials, provide a
      unique mechanism to spatially decode parallel fiber signals into cerebellar
      circuitry changes.

PMID- 19104666
TI  - Estimating the confidence level of white matter connections obtained with MRI
      tractography.
AB  - BACKGROUND: Since the emergence of diffusion tensor imaging, a lot of work has
      been done to better understand the properties of diffusion MRI tractography.
      However, the validation of the reconstructed fiber connections remains
      problematic in many respects. For example, it is difficult to assess whether a
      connection is the result of the diffusion coherence contrast itself or the simple
      result of other uncontrolled parameters like for example: noise, brain geometry
      and algorithmic characteristics. METHODOLOGY/PRINCIPAL FINDINGS: In this work, we
      propose a method to estimate the respective contributions of diffusion coherence
      versus other effects to a tractography result by comparing data sets with and
      without diffusion coherence contrast. We use this methodology to assign a
      confidence level to every gray matter to gray matter connection and add this new
      information directly in the connectivity matrix. CONCLUSIONS/SIGNIFICANCE: Our
      results demonstrate that whereas we can have a strong confidence in mid- and long
      range connections obtained by a tractography experiment, it is difficult to
      distinguish between short connections traced due to diffusion coherence contrast
      from those produced by chance due to the other uncontrolled factors of the
      tractography methodology.

PMID- 19104667
TI  - Genomic organization and expression demonstrate spatial and temporal Hox gene
      colinearity in the lophotrochozoan Capitella sp. I.
AB  - Hox genes define regional identities along the anterior-posterior axis in many
      animals. In a number of species, Hox genes are clustered in the genome, and the
      relative order of genes corresponds with position of expression in the body.
      Previous Hox gene studies in lophotrochozoans have reported expression for only a
      subset of the Hox gene complement and/or lack detailed genomic organization
      information, limiting interpretations of spatial and temporal colinearity in this
      diverse animal clade. We studied expression and genomic organization of the
      single Hox gene complement in the segmented polychaete annelid Capitella sp. I.
      Total genome searches identified 11 Hox genes in Capitella, representing 11
      distinct paralog groups thought to represent the ancestral lophotrochozoan
      complement. At least 8 of the 11 Capitella Hox genes are genomically linked in a
      single cluster, have the same transcriptional orientation, and lack interspersed
      non-Hox genes. Studying their expression by situ hybridization, we find that the
      11 Capitella Hox genes generally exhibit spatial and temporal colinearity. With
      the exception of CapI-Post1, Capitella Hox genes are all expressed in broad
      ectodermal domains during larval development, consistent with providing
      positional information along the anterior-posterior axis. The anterior genes CapI
      lab, CapI-pb, and CapI-Hox3 initiate expression prior to the appearance of
      segments, while more posterior genes appear at or soon after segments appear.
      Many of the Capitella Hox genes have either an anterior or posterior expression
      boundary coinciding with the thoracic-abdomen transition, a major body tagma
      boundary. Following metamorphosis, several expression patterns change, including
      appearance of distinct posterior boundaries and restriction to the central
      nervous system. Capitella Hox genes have maintained a clustered organization, are
      expressed in the canonical anterior-posterior order found in other metazoans, and
      exhibit spatial and temporal colinearity, reflecting Hox gene characteristics
      that likely existed in the protostome-deuterostome ancestor.

PMID- 19104668
TI  - A recurrent network in the lateral amygdala: a mechanism for coincidence
      detection.
AB  - Synaptic changes at sensory inputs to the dorsal nucleus of the lateral amygdala
      (LAd) play a key role in the acquisition and storage of associative fear memory.
      However, neither the temporal nor spatial architecture of the LAd network
      response to sensory signals is understood. We developed a method for the
      elucidation of network behavior. Using this approach, temporally patterned
      polysynaptic recurrent network responses were found in LAd (intra-LA), both in
      vitro and in vivo, in response to activation of thalamic sensory afferents.
      Potentiation of thalamic afferents resulted in a depression of intra-LA synaptic
      activity, indicating a homeostatic response to changes in synaptic strength
      within the LAd network. Additionally, the latencies of thalamic afferent
      triggered recurrent network activity within the LAd overlap with known later
      occurring cortical afferent latencies. Thus, this recurrent network may
      facilitate temporal coincidence of sensory afferents within LAd during
      associative learning.

PMID- 19104669
TI  - Babies and brains: habituation in infant cognition and functional neuroimaging.
AB  - Many prominent studies of infant cognition over the past two decades have relied
      on the fact that infants habituate to repeated stimuli - i.e. that their looking
      times tend to decline upon repeated stimulus presentations. This phenomenon had
      been exploited to reveal a great deal about the minds of preverbal infants. Many
      prominent studies of the neural bases of adult cognition over the past decade
      have relied on the fact that brain regions habituate to repeated stimuli - i.e.
      that the hemodynamic responses observed in fMRI tend to decline upon repeated
      stimulus presentations. This phenomenon has been exploited to reveal a great deal
      about the neural mechanisms of perception and cognition. Similarities in the
      mechanics of these two forms of habituation suggest that it may be useful to
      relate them to each other. Here we outline this analogy, explore its nuances, and
      highlight some ways in which the study of habituation in functional neuroimaging
      could yield novel insights into the nature of habituation in infant cognition -
      and vice versa.

PMID- 19104671
TI  - One-pot preparation of substituted pyrroles from alpha-diazocarbonyl compounds.
AB  - In this work an efficient one-pot synthesis of substituted pyrroles 7a-n is
      described, which involves the in situ formation of dihydrofurans ethyl 5-butoxy-2
      methyl-4,5-dihydrofuran-3-carboxylate (4), 1-(5-butoxy-2-methyl-4,5-dihydrofuran
      3-yl)ethanone (5) and 5-butoxy-4,5-dihydrofuran-3-carbaldehyde (6) followed by
      reaction with primary amines.

PMID- 19104670
TI  - Representational similarity analysis - connecting the branches of systems
      neuroscience.
AB  - A FUNDAMENTAL CHALLENGE FOR SYSTEMS NEUROSCIENCE IS TO QUANTITATIVELY RELATE ITS
      THREE MAJOR BRANCHES OF RESEARCH: brain-activity measurement, behavioral
      measurement, and computational modeling. Using measured brain-activity patterns
      to evaluate computational network models is complicated by the need to define the
      correspondency between the units of the model and the channels of the brain
      activity data, e.g., single-cell recordings or voxels from functional magnetic
      resonance imaging (fMRI). Similar correspondency problems complicate relating
      activity patterns between different modalities of brain-activity measurement
      (e.g., fMRI and invasive or scalp electrophysiology), and between subjects and
      species. In order to bridge these divides, we suggest abstracting from the
      activity patterns themselves and computing representational dissimilarity
      matrices (RDMs), which characterize the information carried by a given
      representation in a brain or model. Building on a rich psychological and
      mathematical literature on similarity analysis, we propose a new experimental and
      data-analytical framework called representational similarity analysis (RSA), in
      which multi-channel measures of neural activity are quantitatively related to
      each other and to computational theory and behavior by comparing RDMs. We
      demonstrate RSA by relating representations of visual objects as measured with
      fMRI in early visual cortex and the fusiform face area to computational models
      spanning a wide range of complexities. The RDMs are simultaneously related via
      second-level application of multidimensional scaling and tested using
      randomization and bootstrap techniques. We discuss the broad potential of RSA,
      including novel approaches to experimental design, and argue that these ideas,
      which have deep roots in psychology and neuroscience, will allow the integrated
      quantitative analysis of data from all three branches, thus contributing to a
      more unified systems neuroscience.

PMID- 19104672
TI  - Synthesis of imidazol-1-yl-acetic acid hydrochloride: a key intermediate for
      zoledronic acid.
AB  - A convenient and practical synthesis of imidazol-1-yl-acetic acid hydrochloride
      was achieved via N-alkylation of imidazole using tert-butyl chloroacetate
      followed by a non-aqueous ester cleavage of the resulting imidazol-1-yl-acetic
      acid tert-butyl ester in the presence of titanium tetrachloride. The synthesized
      imidazol-1-yl-acetic acid hydrochloride was then utilized to prepare zoledronic
      acid.

PMID- 19104673
TI  - Synthesis of chiral cyclohexanes and carbasugars by 6-exo-dig radical cyclisation
      reactions.
AB  - Treatment of 5-(tert-butyldimethylsilyl)-2,3-O-isopropylidene-D-ribose with
      lithium acetylides gave mixtures of syn- and anti-alkynols 2a-2c which were
      separated following protection as methoxymethyl ethers. These were converted to
      the corresponding iodides which underwent 6-exo-dig radical cyclisation to afford
      chiral cyclohexanes and carbasugars. Oxidation of the primary alcohols 6a-b gave
      the corresponding aldehydes which on treatment with Grignard reagents afforded a
      mixture of alcohols. The corresponding iodides underwent similar 6-exo-dig
      cyclisation to give fully functionalised cyclohexanes.

PMID- 19104674
TI  - Convenient method for preparing benzyl ethers and esters using 2
      benzyloxypyridine.
AB  - 2-Benzyloxy-1-methylpyridinium triflate (1) is emerging as a mild, convenient,
      and in some cases uniquely effective new reagent for the synthesis of benzyl
      ethers and esters. This article provides a revised benzyl transfer protocol in
      which N-methylation of 2-benzyloxypyridine delivers the active reagent in situ.
      Observations on the appropriate choice of solvent (toluene vs. trifluorotoluene)
      and the extension of this methodology to the synthesis of other arylmethyl ethers
      are included.

PMID- 19104675
TI  - Synthesis of 2,3,6,7-tetrabromoanthracene.
AB  - The first synthesis of 2,3,6,7-tetrabromoanthracene is presented, starting from
      benzene in a straightforward four step synthesis.

PMID- 19104677
TI  - The role of ACAID and CD4+CD25+FOXP3+ regulatory T cells on CTL function against
      MHC alloantigens.
AB  - PURPOSE: Anterior chamber associated immune deviation (ACAID) is an antigen
      specific form of peripheral immune tolerance that is induced to exogenous
      antigens placed in the ocular anterior chamber, which leads to a suppression in
      delayed-type hypersensitivity (DTH). Considerable work has been done on ACAID
      induction to major histocompatibility (MHC) alloantigens. However, its role on
      cytotoxic T lymphocyte (CTL) activity is currently unknown. METHODS: C57BL/6 (H
      2(b)) mice received an intracameral (IC) inoculation with BALB/c (H-2(d))
      splenocytes. Splenic CD4(+) and CD8(+) T cell populations were characterized by
      flow cytometry and proliferation assays during induction and expression phases of
      ACAID. Percentages of CD4(+)CD25(+)FoxP3(+) T regulatory cells (Treg) were also
      followed. Lastly, CTL function was measured at various time points during ACAID
      expression, and Treg were added to identify potential alterations in CTL
      function. RESULTS: CD4(+) and CD8(+) T cell percentages and proliferation
      increased in the spleen during ACAID induction but then sharply decreased in
      response to an allospecific immunization. Expression of ACAID also exhibited a
      significant drop in CTL function. However, while Treg expansion was observed,
      these cells did not directly mediate the CTL inhibition. CONCLUSIONS: ACAID
      mediates an inhibition of CTL function against MHC alloantigens. Furthermore, we
      found that ACAID induction leads to the expansion and proliferation of CD4(+) and
      CD8(+) T cells while ACAID expression is associated with a diminishment in T cell
      percentages due to proliferation impairment. Lastly, Treg also expand during
      ACAID induction. However, our data suggest that Treg do not directly inhibit CTL
      activity.

PMID- 19104676
TI  - Expressed sequence tag analysis of guinea pig (Cavia porcellus) eye tissues for
      NEIBank.
AB  - PURPOSE: To characterize gene expression patterns in guinea pig ocular tissues
      and identify orthologs of human genes from NEIBank expressed sequence tags.
      METHODS: RNA was extracted from dissected eye tissues of 2.5-month-old guinea
      pigs to make three unamplified and unnormalized cDNA libraries in the pCMVSport-6
      vector for the lens, retina, and eye minus lens and retina. Over 4,000 clones
      were sequenced from each library and were analyzed using GRIST for clustering and
      gene identification. Lens crystallin EST data were validated using two
      dimensional electrophoresis (2-DE), matrix assisted laser desorption (MALDI), and
      electrospray ionization mass spectrometry (ESIMS). RESULTS: Combined data from
      the three libraries generated a total of 6,694 distinctive gene clusters, with
      each library having between 1,000 and 3,000 clusters. Approximately 60% of the
      total gene clusters were novel cDNA sequences and had significant homologies to
      other mammalian sequences in GenBank. Complete cDNA sequences were obtained for
      many guinea pig lens proteins, including alphaA/alphaAinsert-, gammaN-, and
      gammaS-crystallins, lengsin and GRIFIN. The ratio of alphaA- to alphaB-crystallin
      on 2-DE gels was 8: 1 in the lens nucleus and 6.5: 1 in the cortex. Analysis of
      ESTs, genome sequence, and proteins (by MALDI), did not reveal any evidence for
      the presence of gammaD-, gammaE-, and gammaF-crystallin in the guinea pig.
      Predicted masses of many guinea pig lens crystallins were confirmed by ESIMS
      analysis. For the retina, orthologs of human phototransduction genes were found,
      such as Rhodopsin, S-antigen (Sag, Arrestin), and Transducin. The guinea-pig
      ortholog of NRL, a key rod photoreceptor-specific transcription factor, was also
      represented in EST data. In the 'rest-of-eye' library, the most abundant
      transcripts included decorin and keratin 12, representative of the cornea.
      CONCLUSIONS: Genomic analysis of guinea pig eye tissues provides sequence
      verified clones for future studies. Guinea pig orthologs of many human eye
      specific genes were identified. Guinea pig gene structures were similar to their
      human and rodent gene counterparts. Surprisingly, no orthologs of gammaD-, gammaE
      , and gammaF-crystallin were found in EST, proteomic, or the current guinea pig
      genome data.

PMID- 19104678
TI  - Th1- and Th2-related chemokine and chemokine receptor expression on the ocular
      surface in endotoxin-induced uveitis.
AB  - PURPOSE: To determine whether the ocular surface inflammation in uveitis mimics
      or counteracts intraocular inflammatory pathways by directly comparing T-helper
      (Th) lymphocytes Th1 and Th2 markers in conjunctival and ciliary body expression
      in endotoxin-induced uveitis (EIU). This study used the following inflammatory
      markers: chemokine receptor, CC chemokine receptor 4 (CCR4), and its ligand,
      macrophage-derived chemokine (MDC), to evaluate Th2 participation; chemokine
      receptor, CCR5, to evaluate the Th1 system; and its ligand, regulated on
      activation normal T cell expressed and secreted (RANTES), to evaluate both Th1
      and Th2 systems. METHODS: Immunohistochemistry and real-time polymerase chain
      reaction (RT-PCR) were used to compare protein and RNA expression of CCR4, MDC,
      CCR5, and RANTES in the conjunctiva and ciliary body in EIU 6 h and 24 h after
      the lipopolysaccharide (LPS) injection and in control (without injection) Lewis
      rats. RESULTS: Immunohistochemistry with CCR5, RANTES, and MDC showed an increase
      in fluorescent staining in the conjunctiva and ciliary body in the rats with
      uveitis compared to the control rats. For CCR4, immunostaining was comparable in
      the conjunctiva and ciliary body and did not show any clear differences between
      control rats and rats with EIU. For RANTES, MDC, and CCR5, RT-PCR showed a
      significantly higher RNA expression in conjunctiva and in ciliary body at 6 h
      compared to 24 h and controls. For CCR4, RT-PCR did not illustrate any
      significant differences in conjunctiva and in ciliary body between all groups of
      animals. CONCLUSIONS: Protein and RNA expressions of RANTES, MDC, and CCR5 were
      higher in EIU rats than in control rats in the conjunctiva and ciliary body
      whereas the CCR4 level was not modified in the conjunctiva and ciliary body of
      EIU rats when compared to controls. Th1 activation seemed to predominate in this
      model with high levels of CCR5 expression and no increased expression of CCR4,
      but Th2 participation with MDC was noted. The expression of RANTES, MDC, CCR4 and
      CCR5 in EIU was quite similar between the conjunctiva and the ciliary body, so
      conjunctival inflammation might reproduce the intraocular inflammation, probably
      generated by local extension and diffusion in this model. If the ocular surface
      mimics intraocular inflammatory pathways, the conjunctiva may provide a new and
      easier access for uveitis studies.

PMID- 19104680
TI  - Chronic exertional compartment syndrome.

PMID- 19104681
TI  - A conversation with AAOS President E. Anthony Rankin, MD. Interview by Peter D.
      McCann.

PMID- 19104679
TI  - Phosphorylated neurofilament heavy chain is a marker of neurodegeneration in
      Leber hereditary optic neuropathy (LHON).
AB  - PURPOSE: To determine the profile of neurodegeneration in Leber hereditary optic
      neuropathy (LHON). METHODS: We quantitated serum levels of phosphorylated
      neurofilament heavy chain (pNF-H) in a Brazilian pedigree of 16 affected patients
      and 59 carriers with LHON, both molecularly characterized as harboring the G to A
      mutation at nucleotide 11,778 of the mitochondrial genome. The association of
      subject characteristics to pNF-H levels was studied with multiple regression; pNF
      H data were square-root transformed to effect normality of distribution of
      residuals. Relationships between the square-root of pNF-H and age and sex were
      investigated within groups with Pearson correlation and the two-sample t-test.
      Linear regression was used to assess the difference between groups and to
      determine if the relationship of age was different between affected individuals
      and carriers. Results of plotting pNF-H levels by age suggested a nonlinear,
      quadratic association so age squared was used in the statistical analysis. ANCOVA
      was used to assess the influence of age and group on pNF-H levels. RESULTS: In
      the carrier group, there was a significant correlation of square-root pNF-H
      (mean=0.24 ng/ml(2)) with age (r=0.30, p=0.022) and a stronger correlation with
      quadratic age (r=0.37, p=0.003). With a higher mean pNF-H (0.33 ng/ml(2)) for the
      affected group, correlations were of similar magnitude, although they were not
      statistically significant: age (r=0.22, p=0.42), quadratic age (r=0.22, p=0.45).
      There was no correlation between age and pNF-H levels (mean=0.34 ng/ml(2)) in the
      off-pedigree group: age (r=0.03, p=0.87), quadratic age (r=0.04, p=0.84). There
      was no difference between sexes and pNF-H levels in any of the groups (affected,
      p=0.65; carriers, p=0.19; off-pedigree, p=0.93). CONCLUSIONS: Elevated pNF-H
      released into the serum of some affected LHON patients may suggest that axonal
      degeneration occurs at some point after loss of visual function. Increases in pNF
      H levels of carriers with increasing age, not seen in off-pedigree controls, may
      suggest subtle subclinical optic nerve degeneration.

PMID- 19104682
TI  - Cauda equina syndrome: a comprehensive review.
AB  - Cauda equina syndrome (CES) is a rare syndrome that has been described as a
      complex of symptoms and signs--low back pain, unilateral or bilateral sciatica,
      motor weakness of lower extremities, sensory disturbance in saddle area, and loss
      of visceral function--resulting from compression of the cauda equina. CES occurs
      in approximately 2% of cases of herniated lumbar discs and is one of the few
      spinal surgical emergencies. In this article, we review information that is
      critical in understanding, diagnosing, and treating CES.

PMID- 19104683
TI  - Identification and surgical treatment of primary thoracic spinal stenosis.
AB  - We report the surgical treatment results for 7 patients (4 men, 3 women; mean
      age, 49 years) who presented with myelopathy caused exclusively by primary
      thoracic spinal stenosis, predominantly in the lower thoracic spine. (Patients
      with concurrent ascending lumbosacral degenerative disease were excluded.) All
      patients received extensive nonoperative treatment before referral to our center.
      Surgical treatment consisted of wide posterior decompression and instrumented
      fusion (5 cases), anterior vertebrectomy and fusion (1), and anterior
      vertebrectomy with autograft strut followed by wide posterior decompression and
      instrumented fusion (1). Mean operative time was 313 minutes, mean blood loss was
      944 mL, and there were no major postoperative complications. Minimum follow-up
      was 2 years. Five patients had significant improvement in myelopathy and were
      ambulating normally, 1 had modest improvement in ambulation, and 1 remained
      wheelchair-bound. All patients achieved solid radiographic fusions. After
      presenting these case studies, we review the current literature on treatment
      effectiveness. Primary thoracic spinal stenosis should be considered in patients
      who present with isolated lower extremity myelopathy, particularly when no
      significant pathologic findings are identified in the cervical or lumbosacral
      spine. Expedient wide decompression with concurrent instrumented fusion is
      recommended to prevent late development of spinal instability and recurrent
      spinal stenosis.

PMID- 19104684
TI  - Eight-centimeter segmental ulnar defect treated with recombinant human bone
      morphogenetic protein-2.

PMID- 19104685
TI  - Recombinant activated factor VII as a temporary reversal agent for warfarin
      anticoagulation: a cautionary report on an off-label application.

PMID- 19104686
TI  - Failure of the Vari-Angle Hip Screw System: two cases.

PMID- 19104687
TI  - Hypoplasia of the left superior ramus of the pubis.

PMID- 19104688
TI  - Reconstruction of a chronic distal biceps tendon rupture 4 years after initial
      injury.
AB  - Rupture of the distal biceps insertion can produce, on average, a 40% loss of
      supination strength, a 47% loss of supination endurance, and a 21% to 30% loss of
      flexion strength at the elbow. In acute biceps tendon ruptures in which a patient
      will not tolerate resulting functional deficits, anatomical reinsertion of the
      biceps tendon into the radial tuberosity is usually recommended. The various
      surgical techniques that have been described for anatomical repair of distal
      biceps rupture include passage of the tendon stump through a transosseous tunnel
      and use of suture anchors, interference screws, and EndoButtons (Smith & Nephew,
      Andover, Mass). Reported results for these techniques have mostly been excellent
      with respect to restoration of functionality. Chronic cases, however, may involve
      retraction of the native tendon and extensive scar formation, which preclude
      anatomical repair. In these situations, one of several described reconstructive
      techniques, including use of semitendinosus autograft and Achilles tendon
      allograft, may be needed to reestablish acceptable function. Delayed (< or = 18
      months) reconstruction of chronic ruptures, using allograft soft-tissue
      constructs, has been described in the literature. We present the case of a
      chronic distal biceps rupture reconstructed 4 years after initial injury using a
      single-incision technique with free semitendinosus autograft and EndoButton
      fixation.

PMID- 19104689
TI  - Hamstring injuries.

PMID- 19104690
TI  - Percutaneous achilles tendon repair using ring forceps.
AB  - In this article, we describe a method of percutaneous repair of acute Achilles
      tendon ruptures. We suggest an inexpensive and practical technique, using
      standard ring forceps, that produces results comparable with those obtained with
      Dr. Richard Stern's Achillon apparatus.

PMID- 19104692
TI  - Two case reports of benign and tumor-like lesions of bone.

PMID- 19104693
TI  - Subungual extraosseous chondroma in a finger.

PMID- 19104694
TI  - Tumoral calcinosis presenting as neck pain and mass lesion of the cervical spine.

PMID- 19104695
TI  - Swiss tertiary care center experience challenges the age-cohort effect in
      Helicobacter pylori infection.
AB  - BACKGROUND: The epidemiology of Helicobacter pylori infection reflects the age
      characteristics, developmental status and access to health care of the population
      in a given area. AIM: To assess the influence of demographic variables on the
      prevalence of H. pylori status among patients evaluated in a Swiss university
      medical center. METHODS: Demographic data (i.e. age, gender, place of birth),
      indication for H. pylori testing, history of prior H. pylori eradication therapy,
      medical field and clinical setting of the referring physician were reviewed from
      patient's charts. H. pylori status was assessed by the 13C Urea breath test.
      RESULTS: Patients born in Switzerland had lower rates of positive (13)C Urea
      breath test results compared to those born outside of the country (12/101 [11.9%]
      vs. 67/252 [26.6%]; p=0.003). While there were no differences between males and
      females (p>0.05), patients 50 years and below were more likely to have a positive
      test result compared to those above the age of 50 years (59/106 [28.6%] vs.
      20/147 [13.6%]; p<0.01). There were no major differences in the rate of positive
      13C Urea breath tests in patients with previous history of H. pylori eradication
      and those without. Patients with dyspeptic symptoms and those without had similar
      rates of positive tests (11/61 [18.0%] vs. 68/292 [23.3%]; p=ns). CONCLUSION:
      Epidemiologic characteristics of H. pylori infection in Western countries are
      influenced by changing demographics. Further studies are warranted to investigate
      reasons for the changing trends in the prevalence of H. pylori infection.

PMID- 19104696
TI  - How frequent is celiac disease among epileptic patients?
AB  - BACKGROUND: A variety of neurological disorders have been reported in association
      with celiac disease (CD) including epilepsy, ataxia, neuropathy and multifocal
      leucoencephalopathy. The purpose of this study was to assess the prevalence of CD
      among epileptic patients. METHODS: Our study population consisted of 108
      consecutive unexplained epileptic patients from Epilepsy Clinics. Patients who
      were able to give informed consent were invited to undergo screening for CD in a
      gastroenterology clinic. The diagnosis of CD was determined by IgA anti-tissue
      transglutaminase (t-TG) antibodies and by small intestine biopsy. Histopathologic
      changes were interpreted according to the Marsh classification. RESULTS: A total
      of 108 consecutive epileptic patients (72 females, 36 males) ranging from 2-64
      years (mean: 23.44, SD: 12.1) were studied. Positive IgA anti t-TG were detected
      in 4 of 108 epileptic patients (3.7%), while the known prevalence of CD in the
      study area was 0.6%.The intestinal biopsy confirmed the diagnosis of CD in three
      patients and was interpreted as Marsh I. In the other patient, small intestinal
      biopsy indicated only slightly increased number of intraepithelial lymphocytes.
      There was a significant difference between patients with CD and without CD for
      two symptoms: diarrhea and aphtous lesions (p<0.05). CONCLUSION: Prevalence of CD
      was increased among patients with epilepsy of unknown etiology. It is important
      to investigate CD in any patient with idiopathic epilepsy even in the absence of
      digestive symptoms.

PMID- 19104697
TI  - Costs and efficacy of "on demand" low-dose immunoprophylaxis in HBV transplanted
      patients: experience in the Romanian program of liver transplantation.
AB  - BACKGROUND: HBV in liver transplant (LT) patients is associated with good
      outcomes and the challenges are primarily focused around optimizing prophylactic
      regimens with hepatitis B immune globulin (HBIG) and minimizing related costs.
      AIM: To identify recurrence rates in patients transplanted for HBV or HBV+HDV
      infection in whom a combined "on demand" low-dose HBIG was used, maintaining low
      anti-HBs titres (not below 50 IU/L). METHODS: Medical records of 42 patients
      transplanted for HBV or HBV+HDV induced cirrhosis between April 2000 and
      September 2007 at Fundeni Clinical Institute were analyzed. Patients received
      immunoprophylaxis with lamivudine and HBIG (10,000 IU within anhepatic phase and
      daily within the first postoperative week, followed by 2,500 IU on demand). HBV
      recurrence rates and survival during follow-up were evaluated using the Kaplan
      Meier method. RESULTS: HBV recurrence rate was 4.8% after a median of 1.8 years.
      Three year patient survival rate was 70%. None of the patients died due to liver
      failure related to HBV recurrence. Using our "on demand" low-dose administration
      of HBIG, the total mean cost for HBIG and lamivudine for patient per month of
      survival was 598.3 Eur. The projected monthly cost for the "ideal"
      schedule/patient was 2,017 Eur. CONCLUSION: Individualization of
      immunoprophylaxis after LT for HBV related disease according to the lowest
      protective anti-HBs titers in combination with lamivudine is probably the best
      approach for non-replicative pre-LT patients in terms of costs and efficacy.

PMID- 19104699
TI  - Liver stiffness measurement by transient elastography in clinical practice.
AB  - The AIM of our study was to evaluate the results of transient elastography
      assessment of liver stiffness (LS) in various categories of patients. MATERIAL
      AND METHOD: We performed transient elastography in 986 patients. We evaluated:
      the percentage of cases in which valid measurements could be obtained; the values
      of LS in 40 patients with no history of chronic liver disease ("normal"
      patients); 44 inactive HBsAg carriers; 173 patients with proven liver cirrhosis;
      and the correlation between liver biopsy results and LS in 93 patients with
      chronic HCV hepatitis. RESULTS: We obtained valid measurements of LS in 94.6% of
      the 986 cases. Male gender, younger age and low BMI were positive predictive
      factors for obtaining valid measurements. The mean values of LS were: 5.2+/-1.3
      kPa in "normal" patients, 5.8+/-2.6 kPa in inactive HBsAg carriers, 37.2+/-20.9
      kPa in patients with liver cirrhosis. In patients with chronic HCV hepatitis, we
      found that the mean value of LS in those with METAVIR F>=2 was 8.5+/-4.2 kPa,
      higher than in those with F<2: 5.3+/-1.4 kPa (p=0.0017). In patients with F>=3,
      the mean value of LS was 11.1+/-4.3 kPa, significantly higher than in patients
      with F<3: 6.1+/-2.5 kPa (p<0.0001). CONCLUSIONS: Liver stiffness, as a marker of
      fibrosis, can be evaluated by means of transient elastography in a great majority
      of patients. It is a useful method for the exclusion of significant liver
      fibrosis and for predicting liver cirrhosis. As compared to liver biopsy,
      transient elastography can discern significant fibrosis from no or mild fibrosis.

PMID- 19104698
TI  - Improving nonalcoholic fatty liver disease management by general practitioners: a
      critical evaluation and impact of an educational training program.
AB  - BACKGROUND/AIMS: The epidemic diffusion of nonalcoholic fatty liver disease
      (NAFLD) represents an emerging problem in family medicine. General Practitioners
      (GPs) should pay attention to patients with fatty liver, look at associated
      conditions, identify causal factors and patients at risk of evolution. This study
      aimed to assess GPs' knowledge and practice and a training project impact about
      NAFLD: METHODS: 56 GPs filled a questionnaire before and after attending a
      tailored workshop on NAFLD, and performed a clinical survey in patients with
      persistent hypertransaminasemia including screening and liver biopsy when
      indicated. Four months after a training workshop, GPs were questioned again about
      their practice changes with NAFLD: RESULTS: At baseline, less than 30% of GPs
      considered NAFLD as a cause of persistent hypertransaminasemia; over two-thirds
      thought that NAFLD had a prevalence of 5-10% in the general population; about 50%
      considered hypertransaminasemia as the main indication for liver biopsy in NAFLD;
      their main approach included a low lipid-content diet. Comparison of pre/post
      workshop questionnaires showed significant improvements, despite knowledge on
      diet composition and steatogenic drugs remained poor. Among screened patients
      with hypertransaminasemia, NAFLD had a prevalence of 36% and was associated with
      the metabolic syndrome in more than 50%. Liver biopsy was obtained in 8% of
      NAFLD: Chronic viral hepatitis was better diagnosed than NAFLD (biopsy performed
      in 86% of cases). The training workshop resulted in practice changes concerning
      screening of risk patients, search for NASH and managing NAFLD in chronic viral
      hepatitis. CONCLUSIONS: GPs' knowledge about NAFLD appears barely adequate, thus
      targeted training is essential to improve their knowledge and practice.

PMID- 19104700
TI  - Liver enlargement associated with opportunistic infections in patients with human
      immunodeficiency virus infection.
AB  - BACKGROUND AND AIM: Liver disease is commonly present in human immunodeficiency
      virus (HIV) infection. The aim was to determine the frequency of liver
      enlargement and its association with opportunistic infections in patients with
      HIV infection. PATIENTS AND METHODS: A total of 400 HIV-infected patients were
      investigated. Commercial kits (Ortho EIA; BioRad, ELISA) were used for detection
      of serum specific antibodies to HIV, hepatitis C virus, surface antigen of
      hepatitis B virus, and cytomegalovirus. Liver tissues were stained for various
      microorganisms. The electronic data base SPSS for Windows (version 10.0) was used
      for statistical analysis. A p <0.05 was considered significant. RESULTS:
      Ultrasonographic screening revealed liver enlargement in 63.75% of HIV patients.
      In 40.7% the right lobe size varied from 140 mm to 160 mm. Of those with
      hepatomegaly, 60.7% had AIDS. Hepatitis C and B viruses and Mycobacterium
      tuberculosis were detected in 50%, 29% and 18% of patients, respectively.
      Histological changes were mostly non-specific. Liver pathology depended on the
      degree of cellular immune deficiency, particularly in patients with HBV co
      infection. In a minority of patients (32.5%), the histology revealed
      granulomatous hepatitis. Liver function tests were abnormal in 46%. CONCLUSION:
      Liver enlargement is common in HIV-infected patients mostly in association with
      hepatitis C and B viruses and Mycobacterium tuberculosis.

PMID- 19104701
TI  - Reduced quality of life in patients with chronic viral liver disease as assessed
      by SF12 questionnaire.
AB  - BACKGROUND & AIM: Quality of life may be reduced in patients with chronic liver
      diseases. The purpose of this study was to assess the impact of chronic viral
      liver disease on health-related quality of life (HRQOL). PATIENTS AND METHODS:
      Quality of life was prospectively investigated in 227 patients with chronic viral
      liver disease and 75 controls. The generic Short Form 12 questionnaire was
      applied to measure the HRQOL: Mental and physical component scores were expressed
      as numeric and categorical values (presence/absence of disability). The
      electronic database (SPSS for Windows) was used for statistical analysis with 95%
      confidence intervals. RESULTS: Mental and physical numeric and categorical scores
      for the absence of disability were significantly worse in patients compared with
      controls. Patients were a negative predictive factor for the absence of
      disability on both mental and physical components while the physical component
      was the significant factor in multivariate regression analysis (p =0.000). There
      was no difference in HRQOL scores among patients with hepatitis C or B virus
      infection. Mental and physical numeric scores were lower in patients with
      cirrhosis. Liver cirrhosis predicted lower components of the absence of
      disability in comparison to chronic hepatitis more influencing the physical
      component (p =0.003). CONCLUSIONS: Chronic viral liver disease reduces and
      predicts a lower quality of life in comparison to a healthy population impairing
      more the physical component. Hepatitis viruses do not influence differently the
      quality of life. Liver cirrhosis has a higher negative impact on the quality of
      life than chronic hepatitis, especially relating to a physical component.

PMID- 19104703
TI  - Prevalence, histology, endoscopic treatment and long-term follow-up of large
      colonic polyps and laterally spreading tumors. The Romanian experience.
AB  - AIMS: We report the prevalence, histological aspect, endoscopic treatment and
      follow-up of colonic polyps of 2 cm or larger and of laterally spreading tumors
      (LSTs) in an eastern European country. METHODS: All consecutive colonoscopies
      carried out over a 1-year period (3,856) in the Endoscopy Department of the 3rd
      Medical Clinic Cluj-Napoca were evaluated. Fifty-two polyps and 12 LSTs of >=2cm
      diameter were found. Size, location and histological aspect of large colonic
      polyps and LSTs were assessed. Endoscopic or surgical resection was recorded. An
      extensive endoscopic and histological follow-up was performed. RESULTS: Median
      size of polyps was 32mm and of LSTs 41mm. Invasive carcinoma was found in 7
      polyps (20.6%) and in 4 LSTs (28.6%). Thirty-six polyps were endoscopically
      resected (69.2%). A complete endoscopic excision was performed in 35 polyps
      (98.6%). Histological complete resection was achieved in 30 polyps (83.3%).
      Thirteen polyps were surgically resected (25%). Eight LSTs were endoscopically
      resected (64.3%) using endoscopic piecemeal resection (EPMR). A complete
      endoscopic excision was performed in three LSTs (37.5%). Three LSTs were
      surgically resected (21.5%). In the polyp group, one patient presented endoscopic
      recurrence (16.6%) at 6 months follow-up. In the LST group, two invasive
      recurrences were present at 3 and 30 months of follow-up. CONCLUSIONS: A complete
      resection can be performed in the majority of large polyps. LSTs larger than
      50mm, incomplete resection and superficial invasive carcinoma were correlated
      with endoscopic recurrence. EPMR might be a curative method for LSTs but an
      accurate endoscopic diagnosis and long-term endoscopic follow-up are mandatory.

PMID- 19104702
TI  - Expression of p53, Bcl-2, VEGF, Ki67 and PCNA and prognostic significance in
      hepatocellular carcinoma.
AB  - BACKGROUND: Hepatocellular carcinoma is one of the most common malignant tumors
      that carry a poor prognosis. To improve the long-term outlook for HCC, an
      accurate prognosis is important. AIMS: To study the immunohistochemical
      expressions of p53, Ki67, Bcl-2, VEGF and PCNA and their potential role as
      prognostic factors in patients with radical resection of hepatocellular
      carcinoma. PATIENTS AND METHODS: Forty-seven formalin-fixed paraffin-embedded
      tumor samples from patients with HCC receiving liver resection were investigated
      immunohistochemically for the expression of cellular proliferation markers PCNA,
      Ki67, p53, Bcl-2 and VEGF and their correlation with tumor characteristics and
      survival time after resection. RESULTS: p53 was expressed in a higher percentage
      (85.7 vs. 42.1%) in undifferentiated histological tumor grades (Edmondson Steiner
      G3/G4 vs. G1/G2). Patients with p53 accumulating tumors showed a worse survival
      than patients with p53 non-accumulating tumors (median 9.5 vs. 16.5 months). Over
      expression of VEGF was found in 38.3% of all HCCs. VEGF expression was
      significantly correlated with p53 expression and recurrence rates. The results
      showed that the labeling index of PCNA and expression of p53 are correlated. The
      high labeling index of PCNA or over-expression of p53 resulted in high risk of
      tumor recurrence, more aggressive growth and poor survival. CONCLUSION: High
      labeling index of PCNA, p53 nuclear accumulation and VEGF high expression are
      associated with poor survival in patients with HCC.

PMID- 19104704
TI  - Feasibility of therapeutic endoscopic retrograde cholangiopancreatography for
      bile duct stones in nonagenarians: a single unit audit.
AB  - BACKGROUND: Little information is available on short and long-term outcome of
      therapeutic endoscopic retrograde colangiopancreatography (ERCP) for
      choledocholithiasis in nonagenarians (>=90 years). The aim of this study was to
      evaluate retrospectively the feasibility of therapeutic ERCP in nonagenarians
      with choledocholithiasis, as compared with patients aged between 75 and 89 years.
      PATIENTS AND METHODS: During a 9-year period, therapeutic ERCP was performed for
      choledocholithiasis in 33 nonagenarian patients (group A) and 272 patients aged
      75 to 89 years (group B). Clinical features, endoscopic findings, interventions,
      early and long-term results of therapeutic ERCP for a mean follow-up of 36 months
      were assessed and compared between the two groups. RESULTS: Group A patients had
      a higher incidence of acute cholangitis, concomitant diseases and gallbladder
      stones, as compared to group B patients. Furthermore, they required an emergency
      procedure, multiple sessions, stent insertion, and needle knife fistulotomy
      significantly more frequently (p<0.001). Group B patients underwent significantly
      more endoscopic manipulations and had a longer procedure time than group A
      patients. Complete bile duct stone clearance was achieved in 24.2% of group A
      patients and in 90.8% of group B patients (p<0.001). No ERCP related deaths
      occurred in group A patients. Cholecystectomy was not routinely performed in
      Group A patients having gallbladder stones. The rate of early and late
      complications was not significantly different between the two age groups.
      CONCLUSION: Therapeutic ERCP and biliary stenting have proved to be a feasible
      treatment option for the management of choledocholithiasis in nonagenarians.

PMID- 19104706
TI  - Quality of life in inflammatory bowel disease: psychometric evaluation of an IBDQ
      cross-culturally adapted version.
AB  - BACKGROUND & AIMS: The health related quality of life (HR-QoL) construct was
      introduced as a requirement to assess the subjective health status. It is a
      multifaceted construct that has contributed to a better understanding of the
      patients' adaptation to his condition. The Inflammatory Bowel Disease
      Questionnaire (IBDQ), a widely used instrument to assess QoL among IBD patients,
      has already shown its validity and reliability. Our aim was to obtain an easier
      revised version of the (IBDQ-R) and to investigate its cross-cultural
      psychometric properties. METHOD: Carried out in a sample of outpatients recruited
      in a specialized University Clinic (n=76), this study began with the translation
      and linguistic validation of a self-report 32-item version of the questionnaire
      with a 7-point Likert type answering system. We assessed thereafter its
      reliability through internal consistencies and also looked into its
      discriminatory power. We also investigated its convergent validity with other
      health status - clinical assessment, SCDAI and CDAI-m - and well-being measures.
      RESULTS: With a Cronbach's alpha = 0.92 for the global scale and a mean 0.82 for
      the subscales, internal consistencies proved adequate. On the other hand,
      discriminatory power was also significant according to the model. Moreover, the
      expected correlations between IBDQ and the clinical assessment, SCDAI, CDAI-m and
      perception of well-being support evidence of IBDQ-R's convergent validity.
      CONCLUSION: This IBDQ revised version is a highly promising instrument to easily,
      yet feasibly and comprehensively, assess the quality of life in inflammatory
      bowel disease; therefore its use in daily practice is worthy to be recommended.

PMID- 19104705
TI  - Pro12Ala polymorphism in the peroxisome proliferator-activated receptor-gamma
      (PPARgamma) gene in inflammatory bowel disease.
AB  - BACKGROUND & AIMS: Peroxisome proliferator-activated receptor-gamma (PPAR-gamma)
      has recently been implicated as an endogenous regulator of cellular proliferation
      and inflammation. Impaired expression of PPAR-gamma in colonic epithelial cells
      in ulcerative colitis (UC) and increased expression in hypertrophic mesenteric
      adipose tissue in Crohn's disease (CD) have been reported. Furthermore, PPAR
      gamma ligands have been shown to inhibit tissue injury associated with immune
      activation in UC. Any mutation in PPAR-gamma gene may be responsible for the
      increase in inflammatory mediators and hence the perpetuation of inflammation in
      inflammatory bowel disease (IBD) patients. One common polymorphism in PPAR-gamma
      gene is proline to alanine substitution (Pro12Ala) which results from a CCA to
      GCA missense substitution in codon 12 of exon 2 of the PPAR-gamma gene. In this
      study, we aimed to explore Pro12Ala polymorphism in PPAR-gamma gene in IBD in
      Turkish patients. METHODS: 69 patients with CD, 45 with UC and 100 controls of
      similar age and sex were studied. Genomic DNA was isolated from peripheral blood
      leucocytes and mutagenically separated-polymerase chain reaction (PCR) analyses
      were performed to determine the Pro12Ala polymorphism of the PPAR-gamma gene.
      RESULTS: We observed no significant differences in the frequency of the Pro12Ala
      polymorphism in the PPAR-gamma gene among subjects with CD, UC and controls
      (15.9%, 15.5% and 13%, respectively, p>0.05). CONCLUSION: These results suggest
      that Pro12Ala polymorphism in the PPAR-gamma gene relates neither to the risk of
      the development of inflammatory bowel disease nor to the clinical subtypes of CD
      in the Turkish population.

PMID- 19104707
TI  - HBV Chronic hepatitis during chemotherapy - an immune controlled disease.

PMID- 19104708
TI  - QUIZ HQ 48. Oesophageal hiatus hernia and complications of fundoplication.

PMID- 19104709
TI  - IFNalpha-induced recurrence of Graves' disease ten years after thyroidectomy in
      chronic viral hepatitis C. Case report.
AB  - In contrast to chronic or subacute thyroiditis, Graves' disease rarely
      complicates IFN-alpha therapy for chronic viral C hepatitis. We report the case
      of a 51-year-old man in whom IFN-alpha treatment was followed by recurrence of
      Graves' disease 10 years after thyroidectomy was performed and the patient was
      declared cured. Despite severe thyrotoxicosis, combined IFN-alpha and ribavirin
      therapy was continued and radioiodine treatment was considered for Graves'
      disease.

PMID- 19104710
TI  - A case of benign intraductal papillary mucinous neoplasm of the pancreas
      containing two major subtypes.
AB  - Here we report a case of benign intraductal papillary-mucinous neoplasm (IPMN) of
      the pancreas containing two major subtypes. A 73-year-old man underwent
      pancreatoduodenectomy for a cystic mass, 5.0 cm in diameter. Histopathologic
      examinations revealed that IPMN was composed of gastric-type adenoma and
      intestinal-type borderline lesion. Marked intraluminal nodular growth was
      observed in the center of the tumor composed of intestinal-type cells positive
      for MUC2. Our observations suggest that gastric-type epithelium is a precursor of
      intestinal-type lesions in the stepwise progression of IPMN.

PMID- 19104711
TI  - Multiple lymphomatous polyposis associated with small lymphocytic lymphoma: a
      unique presentation.
AB  - Multiple lymphomatous polyposis (MLP) is a rare extra-nodal manifestation of
      lymphoma. In most cases, MLP is associated with mantle cell lymphoma (MCL). We
      report a 66-year-old male diagnosed with small lymphocytic lymphoma (SLL)/chronic
      lymphocytic lymphoma (CLL), who showed evidence of rectal bleeding. A CT-scan of
      the abdomen and pelvis showed an enlarged spleen, multiple paraaortic and
      mesenteric lymph nodes, and some diverticular pouching along the antimesenteric
      border of the pelvic colon. A colonoscopy revealed the presence of multiple
      polypoid lesions, biopsies of which showed diffuse lymphoid infiltrate without
      any identifiable follicles. Immunohistochemical analysis combined with a
      Fluorescence In-Situ Hybridization (FISH) study excluded the diagnosis of MCL. A
      bone marrow aspiration biopsy demonstrated diffuse infiltration of the bone
      marrow with low grade lymphocytes that expressed CD 20, CD5 and CD23, with
      negative BCL-1, t (11; 14) and cyclin D1. A diagnosis of B-cell CLL with kappa
      light chain restriction was made. Multiple lymphomatous polyposis is considered
      to be a digestive counterpart to MCL and can therefore be considered as a
      presentation of MCL. In our case, the polypoid lesions failed to show the
      characteristic features of MCL. The patient's bone marrow revealed a B-cell
      lymphoma of CLL/SLL phenotype, which to our knowledge has not been linked to MLP
      in previously reported cases.

PMID- 19104712
TI  - Laparoscopic excision of an infected "egg-shelled" retroperitoneal pseudocyst.
AB  - Primary retroperitoneal pseudocysts are rare entities. Though laparoscopic
      approach has been described in their treatment, open surgical excision is still
      the mainstay of treatment for these lesions. We present a case of infected
      retroperitoneal pseudocyst and its successful laparoscopic excision. The patient
      was an 80-year old female. Contrast enhanced CT scan of the abdomen and
      ultrasonography confirmed a large retroperitoneal cyst. Laparoscopic resection
      was accomplished after puncturing and decompressing the cyst. There were no
      complications or conversion. The operating time was 176 minutes. The patient was
      discharged 3 days after surgery. Histopathology revealed a pseudocyst.
      Retroperitoneal pseudocysts can be resected laparoscopically with careful and
      meticulous laparoscopic dissection, utilizing the advantages of laparoscopy.

PMID- 19104713
TI  - Real-time sonoelastography - a new application in the field of liver disease.
AB  - Ultrasound elastography is a new imaging technique that allows a noninvasive
      estimation and imaging of tissue elasticity distribution within biological
      tissues using conventional real-time ultrasound equipment with modified software.
      Elastography has been reported to be useful for differentiation and
      characterization of various malignant tumors, such as breast, prostate, thyroid,
      pancreas, lymph nodes, gastrointestinal stromal tumors, hepatocellular carcinoma
      and liver metastasis. Transient and, more recently, real-time elastography has
      been proved to be useful for noninvasive assessment of liver fibrosis in patients
      with diffuse liver diseases. Elasticity imaging promises to make an important
      contribution to ultrasound practice.

PMID- 19104714
TI  - Real-time contrast-enhanced and real-time virtual sonography in the assessment of
      benign liver lesions.
AB  - Imaging techniques, in particular ultrasonography, have led to great advances in
      clinical hepatology in the past few decades. The introduction of second
      generation contrast agents and the development of contrast specific techniques
      have opened new prospects in the detection and characterization of liver lesions.
      New hybrid imaging techniques that combine in real-time transabdominal ultrasound
      with other cross-sectional imaging techniques (CT or MR) might add even more
      valuable information in the cases with focal lesions. The aim of this review is
      to describe the role of real-time contrast-enhanced and real-time virtual
      sonography in the assessment of benign liver lesions.

PMID- 19104716
TI  - Recurrent intrahepatic cholestasis of pregnancy: ursodeoxycholic acid should be
      the first line of treatment.

PMID- 19104717
TI  - Factors associated with gastrointestinal symptom overlap and clustering in a
      predominant Malay Asian population.

PMID- 19104718
TI  - Concomitant colitis in a patient with Behcet's disease.

PMID- 19104719
TI  - Is liver cirrhosis a risk factor for breast cancer in men?

PMID- 19104720
TI  - Achalasia in a 91-year-old patient.

PMID- 19104721
TI  - Histamine, 5-hydroxytriptamine, collagen, mast cells and Ig-secreting cells in
      the small bowel disorders with diarrhea.

PMID- 19104722
TI  - From the editor's desk: the Cardiovascular Journal of South Africa has made
      unprecedented strides in the past 18 months, based on steady progress since its
      inception in 1989.

PMID- 19104723
TI  - A randomised, controlled, double-blind, cross-over pilot study assessing the
      effects of spironolactone, losartan and their combination on heart rate
      variability and QT dispersion in patients with chronic heart failure.
AB  - BACKGROUND AND OBJECTIVE: The blocking of aldosterone or angiotensin II receptors
      improves mortality in patients with chronic heart failure. We explored whether
      combining losartan and spironolactone would have any added benefit on the known
      surrogate of mortality by using heart rate variability (HRV) and QT dispersion as
      our endpoints. METHODS: We designed a three-phase, consecutive, randomised,
      controlled, double-blind, cross-over pilot study to assess the effects of
      losartan alone (50 mg/day), spironolactone (25 mg/day) with angiotensin
      converting enzyme (ACE) inhibitor and, finally, losartan with spironolactone, on
      HRV and QT dispersion. We enrolled eight patients (aged 47 to 72 years, mean =
      63.7 years), with New York Heart Association (NYHA) class II-III heart failure
      and ejection fraction (EF) < 35%, in the study at a university-affiliated
      hospital in Dundee, Scotland. Digital 24-hour Holter recordings were analysed for
      time-domain HRV and the 12-lead ECG was optically scanned and digitised for
      analysis of QT dispersion. Evaluations were done at baseline, and at six, 12 and
      18 weeks from baseline. RESULTS: Losartan and spironolactone showed statistically
      significant, favourable effects on HRV, QT dispersion and mean heart rate (p <
      0.05). CONCLUSION: The data showed that in these patients with heart failure, the
      addition of spironolactone to an ACE inhibitor, or the use of losartan on its
      own, or the combination of losartan plus spironolactone induced a favourable
      sympathovagal balance. The drugs significantly improved HRV indices and QT
      dispersion further, and the combination appeared to be safe. However, no
      significant differences were seen between the effects of each of these regimes on
      HRV and QT dispersion.

PMID- 19104725
TI  - William Nelson ECG quiz.

PMID- 19104724
TI  - In-hospital and mid-term adverse clinical outcomes of a direct stenting strategy
      versus stenting after pre-dilatation for the treatment of coronary artery
      lesions.
AB  - BACKGROUND: Direct stenting without balloon dilatation may reduce procedural
      costs and duration, and hypothetically, the restenosis rate. This study was
      designed to compare the in-hospital and long-term outcomes of direct stenting
      (DS) versus stenting after pre-dilatation (PS) in our routine clinical practice.
      METHODS: The 1 603 patients treated with stenting for single coronary lesions
      were enrolled into a prospective registry. Patients with acute myocardial
      infarction (MI) within the preceding 48 hours, and those with highly calcified
      lesions, total occlusions, or a lesion in a saphenous graft were excluded. The
      baseline, angiographic and procedural data, in-hospital outcomes and follow-up
      data were recorded in our database and analysed with appropriate statistical
      methods. RESULTS: Eight hundred and fifty-seven patients (53.5%) were treated
      with DS and 746 (46.5%) underwent PS. In the DS group, lesions were shorter in
      length, larger in diameter and had lower pre-procedural diameter stenosis. Type C
      and diffuse lesions and drug-eluting stents were found less often (p < 0.001).
      With univariate analysis, dissection and non- Q-wave MI occurred less frequently
      in this group (0.2 and 0.6% vs 3.9 and 2.1%, p < 0.001 and p = 0.01,
      respectively). However, the cumulative major adverse cardiac events (MACE) did
      not differ significantly (4.9 vs 4.6%, p = 0.79). With multivariate analysis,
      direct stenting reduced the risk of dissection (OR = 0.07, 95% CI: 0.01-0.33, but
      neither the cumulative endpoint of MACE (OR = 1.1, 95% CI = 0.58- 2.11, p = 0.7)
      nor its constructing components were different between the groups. CONCLUSIONS:
      Direct stenting in the real world has at least similar long-term outcomes in
      patients treated with stenting after pre-dilatation, and is associated with lower
      dissection rates.

PMID- 19104726
TI  - Validation of a model to predict all-cause in-hospital mortality in vascular
      surgical patients.
AB  - OBJECTIVE: To develop and validate a pre- and postoperative model of all-cause in
      hospital mortality in South African vascular surgical patients. METHODS: We
      carried out a retrospective cohort study. A multivariate analysis using binary
      logistic regression was conducted on a derivation cohort using clinical,
      physiological and surgical data. Interaction and colinearity between covariates
      were investigated. The models were validated using the Homer-Lemeshow goodness-of
      fit test. RESULTS: Independent predictors of in-hospital mortality in the pre
      operative model were: (1) age (per one-year increase) [odds ratio (OR) 1.03, 95%
      confidence interval (CI) 1.0-1.06), (2) creatinine > 180 micromol.l(-1) (OR 6.43,
      95% CI: 3.482-11.86), (3) chronic beta-blocker therapy (OR 2.48, 95% CI: 1.38
      4.48), and (4) absence of chronic statin therapy (OR 2.81, 95% CI: 1.15-6.83).
      Independent predictors of mortality in the postoperative model were: (1) age (per
      one-year increase) (OR 1.05, 95% CI: 1.02-1.09), (2) creatinine > 180 micromol.l(
      1) (OR 5.08, 95% CI: 2.50-10.31), (3) surgery out of hours without statin therapy
      (OR 8.27, 95% CI: 3.36-20.38), (4) mean daily postoperative heart rate (HR) (OR
      1.02, 95% CI: 1.0-1.04), (5) mean daily postoperative HR in the presence of a
      mean daily systolic blood pressure of less than 100 beats per minute or above 179
      mmHg (OR 1.02, 95% CI: 1.01-1.03) and (6) mean daily postoperative HR associated
      with withdrawal of chronic beta-blockade (OR 1.02, 95% CI: 1.01-1.03). Both
      models were validated. CONCLUSION: The pre-operative model may predict the risk
      of in-hospital mortality associated with vascular surgery. The postoperative
      model may identify patients whose risk increases as a result of surgical or
      physiological factors.

PMID- 19104727
TI  - FDG-PET and MIBI-Tc SPECT as follow-up tools in a patient with cardiac
      sarcoidosis requiring a pacemaker.
AB  - A 63-year-old man presented with recent-onset symptoms secondary to third-degree
      atrio-ventricular block, for which a dual-chamber pacemaker was inserted.
      Additional investigations resulted in the diagnosis of cardiac sarcoidosis. FDG
      PET and MIBI-technetium SPECT were used as follow-up tools for monitoring active
      granulomatous myocardial infiltration.

PMID- 19104729
TI  - Hatter Institute Cardiac Horizons series.

PMID- 19104731
TI  - Heparin-induced thrombocytopaenia.
AB  - Heparin-induced thrombocytopaenia (HIT) is an acquired, transient prothrombotic
      disorder caused by heparin. The predominant problem is the creation of a
      prothrombotic milieu, accompanied by a fall in the platelet count. This explains
      the apparent paradox of thrombosis in the face of thrombocytopaenia and why non
      heparin antithrombotic agents are integral to its management.

PMID- 19104728
TI  - Ischaemic postconditioning: from bench to bedside ...
AB  - The increase in the incidence of ischaemic heart disease and acute myocardial
      infarction (AMI) in both high- and low-income countries necessitates the
      development of myocardial salvaging/protection interventions, to be applied
      alongside standard reperfusion therapies. Although the phenomenon of ischaemic
      preconditioning (IPC) is associated with the desired protective capacity, the
      necessity of its application before sustained ischaemia limits its clinical
      potential. The recently described phenomenon of postconditioning (postC), or
      short cycles of reperfusion/ischaemia applied at the onset of reperfusion, falls
      within the clinically relevant time period of reperfusion, but can it elicit
      reliable and potent cardioprotection? The answer to this problem is intimately
      related to the question whether postC can be translated from a laboratory
      technique to a clinical therapy. In this brief overview of postconditioning, the
      experimental set-ups and postC algorithms utilised, and their associated outcomes
      in all animal models studied (dog, rabbit, mouse, rat and pig) are discussed. The
      therapeutic potential of postC is also addressed by discussing reported
      preliminary studies on the efficacy and feasibility of postC (both ischaemic and
      pharmacological) in humans.

PMID- 19104732
TI  - Cardio News: jump on the bus of opportunity.

PMID- 19104733
TI  - Impact of recent trial results on cardiovascular risk management (Hatter
      Institute Cardiac Horizons series).

PMID- 19104734
TI  - Low-risk older patients (50 years and older) with raised high-sensitivity CRP (hs
      CRP) benefit from rosuvastatin therapy: the JUPITER study.

PMID- 19104735
TI  - Letters to the editor: comments on the BEAUTIfUL study.

PMID- 19104736
TI  - Heart failure patients with preserved left ventricular ejection fraction did not
      benefit from additional ARB therapy.

PMID- 19104737
TI  - Cardio News: SA Heart 2008.

PMID- 19104738
TI  - Factors influencing the response to postal questionnaire surveys about
      respiratory symptoms.
AB  - BACKGROUND: Response rates to postal questionnaires have been falling in recent
      years. AIM: To examine factors affecting the response to five postal respiratory
      questionnaire surveys. DESIGN: Cross sectional study. SETTING: General practice.
      METHOD: Five surveys were conducted in all adults registered with two UK general
      practices using an ECRHQ-based questionnaire, with two reminders at 4-week
      intervals. RESULTS: Response rates declined over time (1993 - 71.2%; 1995 -
      70.5%; 1999 - 65.5%; 2001 - 65.3%; 2004 - 46.9%). Age and gender of non
      responders were available for 2001 and 2004: responders were older (mean 48.8
      years vs 37.6, p<0.001; 50.5 vs 38.8, p<0.001) and more likely to be female
      (54.9% vs 44.9%, p<0.001; 55.3% vs 48.5%, p<0.001). The response rate was
      increased by 18% (2004) and 23% (2001) by the use of two reminders. Early
      responders were older and more likely to be females, but were less likely to
      smoke than late responders after reminders. There was no important association
      between respiratory symptoms and associated feature prevalence and stage of
      response. CONCLUSION: Declining response rates may represent reduced motivation
      and reluctance to share personal information. Qualitative exploration of late/non
      response could help reduce bias when planning and analysing such surveys. The use
      of two reminders is an important factor in improving response.

PMID- 19104739
TI  - Pediculus humanus capitis: an update.
AB  - Head lice infestation, or pediculosis capitis, caused by Pediculus humanus
      capitis, is a common health concern. In the US, where pediculosis capitis is the
      most prevalent parasitic infestation of children, 6 to 12 million people are
      affected every year. Pediculosis capitis remains confined to the scalp. Scalp
      pruritus is the cardinal symptom, although patients with lice can be
      asymptomatic. Pruritus with impetiginization should prompt the physician to look
      for lice or viable nits. All close contacts should be examined. Treatment
      directed at killing the lice and the ova should be considered only if active lice
      or viable eggs are observed. The three fundamental effective treatment options
      for head lice are topical pediculicides, wet combing, and oral therapy. Spraying
      or fogging a home with insecticides or pediculicides is not recommended.

PMID- 19104740
TI  - Beta-carotene in dermatology: Does it help?
AB  - UV irradiation of the skin leads to the induction of free radicals,
      carcinogenesis, and skin aging, and thus the use of beta-carotene in humans as a
      chaperoning agent is discussed. In the photohemolysis model, beta-carotene
      protects against the phototoxic effects of porphyrins. Beta-carotene should be
      used in erythropoietic protoporphyria, photosensitive diseases, and to reduce the
      effects of phototoxic drugs. Its effects on aging skin and on actinic keratosis
      have not yet been sufficiently studied.

PMID- 19104741
TI  - Cutaneous metastases from internal cancers.
AB  - BACKGROUND: Cutaneous metastases (CMs) from carcinoma are relatively uncommon,
      being usually late events in the course of internal malignancies. CMs from
      internal tumors seen at a secondary dermatological centre in Tunis are reported.
      METHODS: A retrospective review of the available clinical records and
      histological material of all patients with CMs from internal malignancies was
      performed over a 14-year period. RESULTS: Fourteen cases of CMs were recorded: 8
      males and 6 females. The age range was 53 to 96 years, with a mean of 63.5 years
      for males and 76.5 years for females. CMs represented the first indication of an
      internal malignancy in 64% of cases. Firm solitary or multiple nodules were the
      most relevant clinical presentation (93%). Preferred sites were the thorax (50%),
      the abdomen (29%), and the head and neck region (21%). The common sites of
      primary malignancy were the lungs (38%) in males and breast (33%) in females.
      Four out of 14 patients died within a short follow-up period (mean 9.5 months).
      DISCUSSION: CMs are relatively rare in patients with internal cancers, but they
      may be a presenting sign of such cancers.

PMID- 19104743
TI  - Primary cutaneous T-cell-rich B-cell lymphoma: a case report and literature
      review.
AB  - T-cell-rich B-cell lymphoma (TCRBCL) is a recently recognized B-cell lymphoma
      variant, characterized by a minor population of neoplastic B-cells existing in a
      background of predominant reactive T-lymphocytes. It is a rare entity, accounting
      for approximately 1 to 2% of all non-Hodgkin's lymphomas. It has both nodal and
      extranodal presentation. Primary cutaneous TCRBCL is an extremely rare lymphoma
      and only 16 cases have been documented thus far in the medical literature. We
      report the case of a 46- year-old man that presented with a slowly-growing,
      painless skin nodule on the left temporofrontal region of the scalp. A complete
      surgical excision was performed and histological examination revealed diffuse
      infiltration of the dermis by TCRBCL. A complete surgical excision of the skin
      lesion and systemic chemotherapy seems to have been effective because the patient
      is disease-free 2 years after the initial diagnosis was made. This study reports
      a very rare case of TCRBCL presented primarily in the skin. Because of its
      rarity, it is especially important to make the correct diagnosis using the
      appropriate immunohistochemical stains and apply the proper therapy.

PMID- 19104742
TI  - Granuloma annulare displaying pseudorosettes in Borelia infection.
AB  - AIMS: In 2003, pseudorosettes were described as highly suspicious of infection by
      Borrelia burgdorferi sensu lato in the appropriate clinical context.
      Nevertheless, such a pattern has been described in the literature in other non
      infectious conditions. On the other hand, granuloma annulare (GA) has been
      recently closely associated with infection by Borrelia. We investigated how
      frequently pseudorosettes can be detected in common GA cases confirmed for
      Borrelia by PCR. METHODS AND RESULTS: We studied 13 biopsies of non-interstitial
      GA and 2 biopsies of interstitial GA from patients without clinical suspicion of
      borrelial infection. We also performed immunohistochemical studies in all the
      biopsies, using the CD-68 antibody. Molecular studies with PCR were performed
      with beta-globin PCR (human DNA). Borrelial DNA was confirmed by amplifying the
      OspA gene and intergenic rrf-rrl region. We found histiocytic pseudorosettes in
      13 biopsies (86.66%). Human DNA was successfully amplified from 8 of 13 paraffin
      embedded skin samples. From these we amplified borrelial DNA in 5 of 8 samples.
      Out of the 8 cases in which human DNA was amplified, a correlation between
      pseudorosettes and the molecular tests (Borrelia DNA) was confirmed in 5
      instances. CONCLUSIONS: a) Pseudorosettes are not an unusual finding in common
      granuloma annulare; b) Borrelia is present in (most) cases of granuloma annulare;
      and c) Pseudorosettes seem to be a good morphological sign predictive of
      infection with Borrelia in granuloma annulare.

PMID- 19104744
TI  - Subcutaneous nodule after vaccination with an aluminum-containing vaccine.
AB  - Persistent subcutaneous nodules may arise after vaccination or allergen
      desensitization. The swelling might appear as a result of a specific histiocytic
      reaction to aluminum, which is used in many preparations to hasten immune
      response. A wide range of such vaccines are used in national childhood
      vaccination programs. Such nodules are frequently itchy or painful with local
      skin alterations. The condition tends to resolve spontaneously, although long
      term observation is recommended. We describe the clinical history of a 10-year
      old girl who presented with an itchy subcutaneous nodule that appeared five
      months after her second DiTe revaccination.

PMID- 19104745
TI  - Sarcomatoid squamous cell carcinoma: a long-standing case.
AB  - Sarcomatoid, or spindle cell squamous cell carcinoma (SCSC), is relatively
      uncommon, but may be encountered. It poses a challenge in differential diagnosis
      that includes other spindle cell neoplasms. We present a case where the lesion
      existed for 20 years and raised the potential of chronicity as a factor in
      inducing spindle cell morphology. Detailed immunohistochemical features are
      demonstrated, and discussion of the differential diagnosis is offered. The
      patient was an 89-year-old African-American female with an exophytic and polypoid
      mass of the right upper arm measuring 5.5 x 5.5 x 3.0 cm. The mass had been
      present for the last 20 years, and was gradually and very slowly increasing in
      size. After refusing surgery several times, she finally agreed to have an
      excision. The tumor proved to be SCSC.

PMID- 19104746
TI  - Self-healing Langerhans cell histiocytosis (Hashimoto-Pritzker disease): two
      Tunisian cases.
AB  - Self-healing Langerhans cell histiocytosis (SHLCH) is a rare self-limited variant
      of Langerhans cell histiocytosis that presents at birth or during the neonatal
      period. It was first described by Hashimoto and Pritzker in 1973. Subsequently,
      more than 70 cases have been reported in the literature. Regarding age of onset,
      SHLCH should be divided into congenital SHLCH and rare late-onset type. We report
      here two additional cases of SHLCH in Tunisian infants. We emphasize the need for
      long-term follow-up in such patients.

PMID- 19104749
TI  - Tyrosine hydroxylase phosphorylation after naloxone-induced morphine withdrawal
      in the left ventricle.
AB  - Our previous studies have shown that morphine withdrawal induced hyperactivity of
      cardiac noradrenergic pathways. The purpose of the present study was to evaluate
      the effects of morphine withdrawal on site-specific tyrosine hydroxylase (TH)
      phosphorylation in the rat left ventricle. Dependence on morphine was induced by
      a 7-day s.c. implantation of morphine pellets. Morphine withdrawal was
      precipitated on day 8 by an injection of naloxone (2 mg/kg, s.c.). TH
      phosphorylation was determined by quantitative blot immunolabelling using
      phosphorylation state-specific antibodies. Ninety min after naloxone
      administration to morphine-dependent rats there was an increase in phospho-Ser40
      TH (139.0 +/- 13%, P < 0.05) and Ser31-TH (135.5 +/- 11%, P < 0.05) in the left
      ventricle which is associated with both an increase in total TH levels (114.4 +/-
      4.6%, P < 0.05, P < 0.01) and an enhancement of TH activity (51.0 +/- 11
      dm/microg protein, P < 0.001). When HA-1004 (40 nmol/day), inhibitor of cyclic
      AMP dependent protein kinase (PKA) was infused, concomitantly with morphine, it
      diminished the increase in noradrenaline (NA) turnover, total TH expression
      (95.76 +/- 4.1 %, P < 0.01) and TH phosphorylation at Ser40 (85.5 +/- 11%, P <
      0.01) in morphine-withdrawn rats. In addition, we showed that the ability of
      morphine withdrawal to stimulate phosphorylation at serine 31 is reduced (101.7
      +/- 7.7%, P < 0.05) by SL327 (100 mg/kg, i.p.), an inhibitor of extracellular
      signal-regulated kinase (ERK) activation. The present findings demonstrate that
      the enhancement of total TH expression and the increase of the phosphorylation
      state of TH during morphine withdrawal are dependent on PKA and ERK and suggest
      that these transduction pathways might contribute to the activation of the
      cardiac catecholaminergic neurons in response to morphine- withdrawal.

PMID- 19104752
TI  - Complete genome sequence of Nariva virus, a rodent paramyxovirus.
AB  - Nariva virus (NarPV) was isolated from forest rodents (Zygodontomys b.
      brevicauda) in eastern Trinidad in the early 1960s. Initial classification within
      the family Paramyxoviridae was based mainly on morphological observations
      including the structure of nucleocapsids and virion surface projections. Here, we
      report the characterization of the complete genome sequence of NarPV. The genome
      is 15,276 nucleotides in length, conforming to the rule-of-six, and has a genome
      organization typical of most members of the family, with six transcriptional
      units in the order 3'-N-P-M-F-H-L-5'. The gene junctions contain highly conserved
      gene start and stop signals and a tri-nucleotide intergenic sequence present in
      most members of the subfamily Paramyxovirinae. Sequence comparison studies
      indicate that NarPV is most closely related to Mossman virus, which was isolated
      from wild rats (Rattus leucopus) in Queensland, Australia, in 1970. This study
      confirmed the classification of NarPV as a member of the subfamily
      Paramyxovirinae and established the close genome organization and sequence
      relationship between the two rodent paramyxoviruses isolated almost a decade
      apart and from two locations separated by more than 15,000 km.

PMID- 19104753
TI  - Radiographic progression in weight-bearing joints of patients with rheumatoid
      arthritis after TNF-blocking therapies.
AB  - The aim of the present study was to assess the influence of tumor necrosis factor
      (TNF)-blocking therapies on weight-bearing joints in patients with rheumatoid
      arthritis. Changes in clinical variables and radiological findings in 213 weight
      bearing joints (69 hip joints, 63 knee joints, and 81 ankle joints) of 42
      consecutive patients were investigated at baseline and at 1 year of TNF-blocking
      therapies. Structural damage to the weight-bearing joints was assessed using the
      Larsen scoring method. Detailed comparisons of the sizes and locations of
      erosions were performed for each set of radiographs of the respective joints.
      Assessment of radiographs of the 213 weight-bearing joints indicated progression
      of the Larsen grade in eight joints. Another five joints without Larsen grade
      progression showed apparent radiographic progression of joint damage based on
      increases in bony erosions. Overall, 13 joints (6%) of eight patients (19%)
      showed progression of joint damage after 1 year of TNF-blocking therapies.
      Analysis of each baseline grade indicated that radiographic progression of joint
      damage was inhibited in most grade 0-II joints. On the other hand, all hip and
      knee joints with pre-existing damage of grade III/IV showed apparent progression
      even in patients with good response. The results further suggested that
      radiographic progression may occur in less damaged joints when the patients were
      non-responders to the therapy. Among the weight-bearing joints, ankle joints
      showed different radiographic behavior and four ankle joints displayed
      improvement of radiographic damage. Early initiation of anti-TNF therapy should
      be necessary especially when the patients are starting to show early structural
      damage in weight-bearing joints.

PMID- 19104754
TI  - Plant meristems: CLAVATA3/ESR-related signaling in the shoot apical meristem and
      the root apical meristem.
AB  - The plant meristems, shoot apical meristem (SAM) and root apical meristem (RAM),
      are unique structures made up of a self-renewing population of undifferentiated
      pluripotent stem cells. The SAM produces all aerial parts of postembryonic
      organs, and the RAM promotes the continuous growth of roots. Even though the
      structures of the SAM and RAM differ, the signaling components required for stem
      cell maintenance seem to be relatively conserved. Both meristems utilize cell-to
      cell communication to maintain proper meristematic activities and meristem
      organization and to coordinate new organ formation. In SAM, an essential
      regulatory mechanism for meristem organization is a regulatory loop between
      WUSCHEL (WUS) and CLAVATA (CLV), which functions in a non-cell-autonomous manner.
      This intercellular signaling network coordinates the development of the
      organization center, organ boundaries and distant organs. The CLAVATA3/ESR (CLE)
      related genes produce signal peptides, which act non-cell-autonomously in the
      meristem regulation in SAM. In RAM, it has been suggested that a similar
      mechanism can regulate meristem maintenance, but these functions are largely
      unknown. Here, we overview the WUS-CLV signaling network for stem cell
      maintenance in SAM and a related mechanism in RAM maintenance. We also discuss
      conservation of the regulatory system for stem cells in various plant species.

PMID- 19104755
TI  - A case of central nervous system lymphomatoid granulomatosis; characteristics of
      PET imaging and pathological findings.
AB  - Lymphomatoid granulomatosis (LYG) in the central nervous system (CNS) is an
      uncommon lymphoproliferative disorder with low grade malignant potential. Here we
      report a case of CNS-LYG, in particular, its characteristics of radioisotope
      imaging and pathological findings. A 65-year-old man complained of visual
      disturbance and homonymous hemianopsia was designated. CT and MRI revealed an
      edematous, enhanced irregular and nodular lesion in the right occipital and
      parietal lobes. Although 18F-fluorodeoxyglucose (FDG)-positron emission
      tomography (PET) scan showed low uptake in the lesion, Methionine (MET)-PET scan
      indicated high uptake. Proton magnetic resonance spectroscopy ((1)H-MRS) at 3T
      revealed a decrease of the peak of the N-acetylaspartate (NAA), suggesting a
      possible neoplastic lesion. The patient was diagnosed with CNS-LYG based on the
      surgically removed material showing perivascular infiltration of CD3-positive
      small T-lymphocytes with granulomatous lesions. The post-operative steroid
      therapy was effective and the recurrence or exacerbation has not been observed by
      radiological imaging until now.

PMID- 19104756
TI  - Case control study of dry eye and related ocular surface abnormalities in Ibadan,
      Nigeria.
AB  - BACKGROUND: Tear instability is associated with symptoms of ocular discomfort and
      irritation. Many patients with dry eyes remain untreated due to improper
      diagnoses. OBJECTIVE: To identify symptoms and surface abnormalities associated
      with dry eyes. MATERIALS AND METHODS: One hundred and fifty-six eyes of 78
      subjects attending the Eye Clinic of the University College Hospital Ibadan were
      screened for dry eyes/tear instability using rose Bengal stain (graded 0-9), tear
      break-up time (TBUT), Schirmer's 1 tests, tear meniscus height and a standardised
      symptoms questionnaire. Grades 4-9 rose Bengal staining were considered as
      positive dry eye and were compared with grades 0-3 staining eyes as negative
      controls. RESULTS: Mean tear meniscus height, Schirmer's test and TBUT were lower
      among cases than their corresponding control eyes. The difference between the
      mean Schirmer's test values of cases and their controls were statistically
      significant (P = 0.00 for right eyes and P = 0.002 for left eyes). Rose Bengal
      grades were inversely correlated with the mean Schirmer's values (Pearson
      correlation -0.429, P = 0.05 for right eyes and -0.335, P = 0.03 for left eyes)
      and TBUT (Pearson correlation -0.316, P = 0.05 for right eyes and -0.212, P =
      0.06 for left eyes). About 95.8% of the cases were symptomatic, as opposed to
      70.4% of the controls (P = 0.01, Fisher's exact test) and 95.8% of dry right eyes
      compared to 61.1% of their controls had ocular surface abnormalities (P = 0.001),
      while 89.5% of dry left eyes compared to 62.7% of controls had surface
      abnormalities (P = 0.07). CONCLUSION: A close relationship exists between ocular
      irritation symptoms, surface abnormalities and functional evidence of tear
      instability. Such patients should be treated empirically or screened for dry
      eyes.

PMID- 19104757
TI  - Natural and genetically engineered viral agents for oncolysis and gene therapy of
      human cancers.
AB  - Based on personal acquaintances and experience dating back to the early 1950s,
      the senior author reviews the history of viral therapy of cancer. He points out
      the difficulties encountered in the treatment of human cancers, as opposed by the
      highly successful viral therapy of experimentally maintained tumors in laboratory
      animals, especially that of ascites carcinomas in mice. A detailed account of
      viral therapy of human tumors with naturally oncolytic viruses follows,
      emphasizing the first clinical trials with viral oncolysates. The discrepancy
      between the high success rates, culminating in cures, in the treatment of tumors
      of laboratory animals, and the moderate results, such as stabilizations of
      disease, partial responses, very rare complete remissions, and frequent relapses
      with virally treated human tumors is recognized. The preclinical laboratory
      testing against established human tumor cell lines that were maintained in tissue
      cultures for decades, and against human tumors extricated from their natural
      habitat and grown in xenografts, may not yield valid results predictive of the
      viral therapy applied against human tumors growing in their natural environment,
      the human host. Since the recent discovery of the oncosuppressive efficacy of
      bacteriophages, the colon could be regarded as the battlefield, where incipient
      tumor cells and bacteriophages vie for dominance. The inner environment of the
      colon will be the teaching ground providing new knowledge on the value of the
      anti-tumor efficacy of phage-induced innate anti-tumor immune reactions.
      Genetically engineered oncolytic viruses are reviewed next. The molecular biology
      of viral oncolysis is explained in details. Elaborate efforts are presented to
      elucidate how gene product proteins of oncolytic viruses switch off the oncogenic
      cascades of cancer cells. The facts strongly support the conclusion that viral
      therapy of human cancers will remain in the front lines of modern cancer
      therapeutics. It may be a combination of naturally oncolytic viruses and wild
      type viruses rendered oncolytic and harmless by genetic engineering, that will
      induce complete remissions of human tumors. It may be necessary to co-administer
      certain chemotherapeutic agents, advanced cancer vaccines, or even immune
      lymphocytes, and targeted therapeuticals, to ascertain, that remissions induced
      by the viral agents will remain complete and durable; will co-operate with anti
      tumor host immune reactions, and eventually will result in cures of advanced
      metastatic human cancers.

PMID- 19104758
TI  - Determination of copper and iron in biological samples of viral hepatitis (A-E)
      female patients.
AB  - There is accumulative evidence that the metabolism of iron and copper is altered
      in viral hepatic diseases, and these nutrients might have specific roles in their
      pathogenesis and progress. The aim of present study was to compare the level of
      copper (Cu) and iron (Fe) in biological samples (serum, urine, and scalp hair) of
      female patients suffering from different viral hepatitis (A, B, C, D, and E; n =
      253) of age range 31-45 years. For comparative study, 95 healthy females of the
      same age group residing in the same city were selected. The elements in the
      biological samples were analyzed by flame atomic absorption spectrophotometry,
      prior to microwave-assisted acid digestion. The validity and accuracy of the
      methodology was checked by using certified reference materials (CRMs) and with
      those values obtained by conventional wet acid digestion method on same CRMs. The
      results of this study showed that the mean values of Cu and Fe were higher in
      sera and scalp hair samples of hepatitis patients than age-matched control
      subjects, while the difference was significant (p < 0.001), in the cases of viral
      hepatitis B and viral hepatitis C as compared to viral hepatitis A, D, and E. The
      urinary levels of these elements were found higher in the hepatitis patients than
      in the age-matched healthy controls (p < 0.05). These results are consistent with
      literature-reported data, confirming that hepatic iron and copper overload can
      directly cause lipid peroxidation and eventually hepatic damage.

PMID- 19104759
TI  - Dietary selenium (Se) and copper (Cu) interact to affect homocysteine metabolism
      in rats.
AB  - Previously, we reported that both Se deficiency and Cu deficiency decreased
      plasma homocysteine (pHcys) and increased plasma glutathione (pGSH) in rats. We
      also showed that the catalytic subunit of glutamate-cysteine ligase (Gclc), which
      catalyzes the rate-limiting step in glutathione biosynthesis, was upregulated in
      Se and Cu deficiencies. We suggested that in both deficiencies, Hcys was being
      shunted through the trans-sulfuration pathway as a result of this up-regulation.
      Because both Se and Cu deficiencies have similar effects, we hypothesized that a
      combined deficiency would exacerbate the decrease in pHcys and the increase in
      pGSH by further up-regulating Gclc. In a 2 x 2 experiment, male weanling Sprague
      Dawley rats (n = 8-20/group) were fed an amino-acid-based diet containing either
      0 or 0.2 microg Se (as selenite)/g and <1 or 6 microg Cu (as Cu carbonate)/g for
      5 weeks. Our findings show that a combined deficiency of both Se and Cu results
      in lower pHcys and significantly elevated pGSH. However, the up-regulation of
      liver Gclc alone cannot explain why rats fed with the doubly deficient diet have
      the lowest pHcys and the highest pGSH.

PMID- 19104760
TI  - Expression and purification of human keratinocyte growth factor 2 by fusion with
      SUMO.
AB  - Small ubiquitin-related modifier (SUMO) fusion system has been shown to be
      efficient for enhancing expression and preventing degradation of the target
      protein. We showed herein that SUMO fusion to human keratinocyte growth factor 2
      (hKGF-2) gene was feasible and it significantly enhanced protein expression and
      its efficiency. The fusion DNA fragment composed of SUMO gene, which was fused to
      hexahistidine tag, and hKGF-2 gene was amplified by PCR and inserted into the
      expression vector pET28a to construct the recombinant plasmid, pET28a-SUMO-hKGF
      2. The plasmid was then transformed into Escherichia coli Rosetta(TM)2(DE3), and
      the recombinant fusion protein SUMO-hKGF-2 was expressed at 30 degrees C for 6 h,
      with the induction of IPTG at the final concentration of 0.4 mM. The expression
      level of the fusion protein was up to 30% of the total cellular protein. The
      fusion protein was purified by Ni-NTA affinity chromatography. After desalting by
      Sephadex G-25 size exclusion chromatography, the hexahistidine-SUMO-hKGF-2 was
      digested by SUMO proteases. The recombinant hKGF-2 was purified again with Ni-NTA
      column and the purity was about 95% with a total yield of 13.9 mg/l culture. The
      result of mitogenicity assay suggests that the recombinant hKGF-2 can
      significantly promote the proliferation of normal rat kidney epithelial (NRK-52E)
      cells.

PMID- 19104762
TI  - A biotic ligand model-based toxicodynamic approach to predict arsenic toxicity to
      tilapia gills in cultural ponds.
AB  - Farming of tilapia Oreochromis mossambicus is an important aquacultural activity
      in Taiwan. Due to the elevated arsenic (As) concentration in pond water, it is
      important to assess the bioavailability and toxicity of As to tilapia for
      protection of aquatic life and human health. In the present study, we developed a
      biotic ligand model (BLM)-based toxicodynamic approach to dynamically predict
      both acute and chronic effective concentrations of As to tilapia in two tilapia
      farms located at Pudai and Chiangchun counties in southwestern Taiwan. Parameters
      revealed in the mechanistic model were obtained by fitting this model to the
      toxicokinetic and toxicodynamic data from our previous laboratory experiments.
      Based on our extended BLM concepts, the site-specific water effect ratios and
      ambient water quality criteria can be determined with known water chemistry. The
      proposed methodology was capable of bridging the gap between laboratory toxicity
      bioassays and field investigations. With respect to risk assessments, our
      research may also provide an useful means of generating and adjusting the site
      specific ambient water quality criteria.

PMID- 19104763
TI  - [Therapy-resistant "psoriasis vulgaris"].
AB  - A 61-year-old patient had a 25-year history of erythematous scaling lesions,
      diagnosed and treated as psoriasis vulgaris. He presented with a growing nodule
      within the erythematous plaque. Biopsy shows epithelioid cell granulomas with
      prominent Langhans giant cells. There was no sign of a squamous cell carcinoma.
      The tuberculin test was strongly positive and M. tuberculosis complex was
      detected in the biopsy material by PCR. He was diagnosed with lupus vulgaris, the
      most frequent form of cutaneous tuberculosis. Other types include tuberculosis
      verrucosa cutis, tuberculosis cutis orificialis and disseminated military
      tuberculosis. The patient was treated with rifampicin, isoniazid, pyrazinamide
      and ethambutol for two months, following a four month treatment with rifampicin
      and isoniazid. The skin lesions rapidly resolved under antituberculotic
      treatment.

PMID- 19104764
TI  - [Quality of care after distal radius fracture in Germany. Results of a fracture
      register of 1,201 elderly patients].
AB  - BACKGROUND: This study is the first to document the quality of inpatient care
      provided to elderly patients with distal radius fracture in Germany. PATIENTS AND
      METHODS: Inpatient care provided to 1,201 patients age 65 or older with isolated
      distal radius fracture was documented in a prospective cohort study conducted at
      242 acute care clinics in Germany between January 2002 and September 2003.
      RESULTS: The median patient age was 75, and nearly 90% of patients were female.
      Approximately 71% of patients were classified as ASA I or II, and 28% were ASA
      III. The most common comorbidity was arterial hypertension (60%). Seventy-five
      percent of patients were admitted on the day of the accident; of these, 63% had
      surgery on the same day, and 20% on the following day. The primary form of
      anaesthesia was general anaesthesia (55%). The predominant fracture management
      procedure was percutaneous K-wire osteosynthesis (56% of cases), followed by
      plate osteosynthesis (44%). The length of hospital stay after plate
      osteosynthesis (median 8.5 days) was more than twice as long as after K-wire
      osteosynthesis (median 4 days). The rate of postoperative complications typical
      of each procedure was around 10%. Roughly 90% of patients were discharged to
      home. Although evidence of osteoporosis was observed in 62% of women and 50% of
      men, only 7.9% of patients were prescribed osteoporosis-specific medication.
      CONCLUSIONS: Unexpected findings were the predominance of general anaesthesia and
      percutaneous K-wire osteosynthesis. Osteoporosis, affecting a majority of elderly
      women, is neglected in clinical practice. Good quality of care is reflected by
      the low rate of complications.

PMID- 19104765
TI  - [Quality improvement of multiple choice examinations: in psychiatry,
      psychosomatic medicine, psychotherapy, and neurology].
AB  - We describe a continuous improvement process in planning, performance, and
      evaluation of multiple choice examination questions in psychiatry, neurology,
      psychosomatic medicine, and psychotherapy. We analyzed 640 multiple choice
      questions of 1,419 students during a period of 4 years. Crucial changes concerned
      the abolishment of problematic question types, implementation of validated new
      question formats, extension of case-based questions, elongation of question
      stems, quantitative evaluation of item difficulty, discriminatory value, and the
      introduction of a peer review system. Consequences of these improvements were
      greater item difficulty (average 18%) and discriminatory value (average 67%) and
      reduced post hoc analysis times. Introduction of peer reviews resulted in longer
      preparation time, which was however appreciated by the peers due to a clear
      improvement in item quality.

PMID- 19104766
TI  - [Predicting risk of suicide in bipolar and unipolar depression: correlation
      between temperament and personality].
AB  - OBJECTIVE: The aim of this study was to evaluate the roles of personality and
      affective temperament traits in the prediction of suicide risk in mood disorders.
      METHODS: The participants were 147 psychiatric inpatients with bipolar disorders
      I and II and major depressive disorder. Patients undertook the Temperament
      Evaluation of Memphis, Pisa, Paris, and San Diego self-rating questionnaire, the
      Minnesota Multiphasic Personality Inventory-2 (MMPI-2), and the Beck Hopelessness
      Scale. RESULTS: Sixty-four subjects were diagnosed with increased suicidal risk
      based on the Mini International Neuropsychiatric Interview (MINI). Logistic
      regression analysis resulted in two models predictive of MINI-based suicidal
      risk: irritable temperament and the MMPI-2 scale. Multiple regression analysis
      further indicated that higher hyperthymic values are protective against
      hopelessness, while MINI-based suicidal intent is a predictor of hopelessness.
      CONCLUSIONS: Personality and affective temperament traits may have a role in the
      prediction of suicide.

PMID- 19104767
TI  - [Acute cervical spinal cord infarction following paravertebral infiltration
      treatment].

PMID- 19104768
TI  - [Value of the postoperative Storkel score. Predict disease-free survival of
      patients with surgically resected renal cell carcinoma].
AB  - OBJECTIVE: To determine the value of clinical and pathological parameters
      defining the Storkel score in order to predict outcomes of patients with
      surgically treated renal cell carcinoma (RCC). MATERIAL AND METHODS: A total of
      834 consecutive patients having radical or partial nephrectomy were
      retrospectively reviewed. For each patient with RCC, the prognostic Storkel score
      was calculated according to the following variables: Robson stage, Thoenes
      nuclear grading, histological type, pattern of growth, and age. Based on the
      Storkel score, patients were divided into groups: those with good prognosis (GP),
      intermediate prognosis (IP), and poor prognosis (PP). Cancer-specific survival
      (CSS) and overall survival (OS) were estimated using the Kaplan-Meier method. The
      accuracy of prediction of CSS and OS with the Storkel score was analyzed using
      Kaplan-Meier analysis, proportional hazards regression, and graphic
      representation [(Kaplan-Meier curves, area under the curve (AUC)]. In 564
      patients who were still alive, the median follow-up was 79 months (mean 84.8
      months). RESULTS: In the GP, IP, and PP groups, CSS after 8 years was 86.7%,
      75.6%, and 13.7%, respectively (p<0.001). In the multiple analysis, only the
      Robson stage and Thoenes nuclear grading independently predicted CSS.
      Accordingly, the prognostic accuracy of the Storkel score (CSS prediction:
      AUC=0.744, 95% CI=0.70-0.79) was not better than with a reduced model that
      included the Robson stage and grading only (CSS prediction: AUC=0.765, 95%CI=0.72
      0.81). CONCLUSIONS: Of all parameters included in the Storkel score, only the
      Robson stage and nuclear grading are significant prognostic factors. Hence, we
      recommend an accordant modification of the score with additional variables.

PMID- 19104769
TI  - The effect of salsalate on insulin action and glucose tolerance in obese non
      diabetic patients: results of a randomised double-blind placebo-controlled study.
AB  - AIM/HYPOTHESIS: Low-grade inflammation may contribute to obesity-related insulin
      resistance and has been associated with increased risk of type 2 diabetes
      mellitus. The present study evaluated whether treatment with salsalate, a
      traditional anti-inflammatory medication, would improve insulin action in obese
      non-diabetic individuals. METHODS: The study was a randomised, double-blind,
      placebo-controlled, parallel trial conducted at the inpatient clinical research
      unit of the NIDKK (Phoenix, AZ, USA). Participants were 54 adults (18 to 45 years
      of age) with BMI >or= 30 kg/m(2). The intervention was salsalate (3 g/day, n =
      28) or identical placebo (n = 26) for 7 days. The allocation was kept concealed
      by giving the investigator only a number corresponding to a vial of placebo or
      salsalate sequentially randomised in blocks by sex. Main outcomes were changes in
      insulin action assessed as rate of glucose disposal (R (d)) by euglycaemic
      hyperinsulinaemic clamp (insulin infusion rate 40 mU m(-2) min(-1)) and glucose
      tolerance by 75 g OGTT. RESULTS: The study was completed by 47 participants, of
      which 40 were analysed (salsalate n = 22, placebo n = 18). Salsalate treatment
      resulted in decreased fasting plasma glucose concentration (mean [SD]; 4.83
      [0.28] vs 5.11 [0.33] mmol/l, p = 0.001) and glucose AUC during the OGTT (p =
      0.01), and in increased R (d) (20 [8] vs 18 [6] micromol [kg estimated metabolic
      body size](-1) min(-1), p = 0.002), while there was no significant change in
      these variables with placebo (p > 0.3 for all). The effect of salsalate on R (d)
      disappeared (p = 0.9) after normalising to increased insulin concentrations (701
      [285] vs 535 [201] pmol/l, p < 0.0001) measured during the clamp. No side effects
      of salsalate were observed during the study. CONCLUSIONS/INTERPRETATION: The
      glucose-lowering potential of salicylates appears to be due to effects on insulin
      concentration rather than improved insulin action. Salicylate-based compounds may
      be useful for the treatment and prevention of type 2 diabetes.

PMID- 19104770
TI  - Accumulation of autoreactive effector T cells and allo-specific regulatory T
      cells in the pancreas allograft of a type 1 diabetic recipient.
AB  - AIMS/HYPOTHESIS: Simultaneous kidney-pancreas transplantation is an established
      treatment for patients with type 1 diabetes and end-stage renal failure, even
      though restored beta cell function may become affected by recurrent islet
      autoimmunity or graft rejection. We characterised infiltrating lymphocytes
      isolated from a pancreatic graft with normal endocrine function in a kidney
      pancreas recipient with type 1 diabetes. METHODS: The pancreas graft was removed
      due to recurrent graft pancreatitis of unknown cause. Pancreas-infiltrating
      lymphocytes and peripheral blood mononuclear cells (PBMC) were isolated and
      characterised phenotypically and functionally. RESULTS: Compared with PBMC,
      pancreas-infiltrating lymphocytes exhibited a distinct activation/memory
      phenotype and T cell receptor profile that were indicative of selective
      infiltration of the pancreas. Islet autoreactive CD8(+) T cells could be detected
      in the pancreas and were increased in frequency compared with PBMC. Additionally,
      an augmentation of CD8(+) CD28(-) regulatory T cells was observed in the
      pancreas; these induced expression of the inhibitory receptor immunoglobulin-like
      transcript-3 on antigen-presenting cells in a donor HLA class I-specific manner.
      CONCLUSIONS/INTERPRETATION: These data demonstrate the simultaneous presence of
      regulatory and effector T cells in the pancreas allograft of a recipient with
      type 1 diabetes. They also indicate that circulating islet autoreactive T cells
      may reflect immunological processes in pancreatic tissue, even though their
      frequency in the periphery may lead to underestimation of their presence in the
      pancreas. Additional specificities were also present in the pancreas that were
      undetectable in the circulation.

PMID- 19104772
TI  - Rotator cuff tears: pathology and repair.
AB  - By virtue of its anatomy and function, the rotator cuff is vulnerable to
      considerable morbidity, often necessitating surgical intervention. The factors
      contributing to cuff disease can be divided into those extrinsic to the rotator
      cuff (most notably impingement) and those intrinsic to the cuff (age-related
      degeneration, hypovascularity and inflammation amongst others). In an era of
      emerging biologic interventions, our interventions are increasingly being
      modulated by our understanding of these core processes, many of which remain
      uncertain today. When we do intervene surgically, the techniques we employ are
      particularly challenging in the context of the tremendous pace of advancement.
      Several recent studies have shown that arthroscopic repair gives similar
      functional results to that of mini-open and open procedures, with all the
      benefits of minimally invasive surgery. However, the 'best' repair construct
      remains unknown, with wide variations in surgeon preference. Here we present a
      literature review encompassing recent developments in our understanding of basic
      science in rotator cuff disease as well as an up-to-date evidence-based
      comparison of different techniques available to the surgeon for cuff repair.

PMID- 19104774
TI  - Physico-chemical characterization of a new heteropolysaccharide produced by a
      native isolate of heterofermentative Lactobacillus sp. CFR-2182.
AB  - A heterofermentative Lactobacillus sp. CFR-2182 was isolated from dahi samples
      and it was found to produce 8.0 and 20.5 g/L heteropolysaccharide (HePS) in EPS
      medium (a simplified synthetic medium) and modified MRS broth, respectively,
      after 72 h at 30 degrees C. The total carbohydrate, reducing sugar and moisture
      contents of the purified HePS were 74, 10.6 and 2 g, respectively, per 100 g on
      dry weight basis. The HePS produced in EPS medium had glucose and mannose in 17:1
      ratio. The HePS was non-gelling and non-film forming type. It was completely
      soluble in water and 1 N sodium hydroxide solution. Gel permeation chromatography
      and HPLC analysis indicated considerable heterogeneity of the HePS, having three
      fractions with molecular weights ranging from 3.3 x 10(4) to 1.32 x 10(6) Da. The
      enzymatic hydrolysis of the HePS with pullulanase and alpha-amylase [with alpha(1
      ->4) linkage] indicated the presence of alpha(1-->6) and traces of alpha(1-->4)
      linkages, respectively. NMR analysis of the EPS revealed unique chemical shifts.

PMID- 19104773
TI  - Comparison of the radiological results between fluoroscopy-assisted and
      navigation-guided total knee arthroplasty.
AB  - The efficacy and accuracy of computer navigation have been proved during recent
      years. But most of recent studies focused on the coronal alignment in total knee
      arthroplasty and less on sagittal alignment. We retrospectively compared the
      results of the radiographs of 35 primary TKAs using a non-image based navigation
      system and 36 primary TKAs using fluoroscopy-assisted conventional technique. To
      compare the radiographic results, the following parameters were measured: mean
      mechanical femorotibial angle, mean femorotibial anatomical angle, mean coronal
      femoral component angle, mean coronal tibial component angle, mean sagittal
      femoral component angle, and mean sagittal tibial component angle. The navigation
      TKA showed better accuracy and consistency in mechanical axis deviation, coronal
      femoral component angle, and sagittal tibial component angle. The coronal tibial
      component position was acceptable in both groups. The navigation TKA markedly
      improved the restoration of mechanical axis, but not so much in sagittal femoral
      component position. The fluoroscopy-assisted conventional TKA had a tendency that
      femoral component was inserted in flexed position than in navigation TKA. Unlike
      the fluoroscopy-assisted conventional TKA, the femoral component was inserted in
      slightly extended position in the navigation TKA than expected. In conclusion,
      even though the use of navigation in TKAs help the surgeon to achieve good
      results, the surgeon should know the tendency of extension of the femoral
      component in sagittal plane to avoid anterior notching.

PMID- 19104775
TI  - Reinforcing and subjective effects of methylphenidate in adults with and without
      attention deficit hyperactivity disorder (ADHD).
AB  - RATIONALE: There has been controversy over the abuse potential of methylphenidate
      (MPH) in the context of treatment for attention deficit hyperactivity disorder
      (ADHD). OBJECTIVE: The objective of this study was to compare the reinforcing and
      subjective effects of oral MPH in adults with and without ADHD. MATERIALS AND
      METHODS: Following screening, 33 adults (n = 16 with ADHD; n = 17 free from
      psychiatric diagnoses) completed four pairs of experimental sessions, each of
      which included a sampling session and a self-administration session. During
      sampling sessions, subjects received in randomized order 0 (placebo), 20, 40, and
      60 mg MPH. During self-administration sessions, subjects completed a progressive
      ratio (PR) task to earn portions of the dose received on the corresponding
      sampling session. Subjective effects were recorded throughout all sessions. The
      main outcome measure for the study was the number of ratios completed on the PR
      task. Secondary measures included peak subjective effects and area-under-the
      curve values for subjective effects. RESULTS: Compared to the control group, the
      ADHD group completed more ratios on the PR task. Both groups showed robust
      effects of methylphenidate on subjective endpoints. Main effects of group were
      noted on subjective effects involving concentration and arousal. CONCLUSIONS:
      Compared to placebo, MPH produced reinforcing effects only for the ADHD group and
      not for the control group. Increases in stimulant-related subjective effects in
      non-ADHD subjects were not associated with drug reinforcement.

PMID- 19104777
TI  - Ionic liquids as desorption solvents and memory effect suppressors in
      heterocyclic aromatic amines determination by SPME-HPLC fluorescence.
AB  - The beneficial effects of 1-butyl-3-methylimidazolium tetrafluoroborate (BMIm
      BF(4)) ionic liquid (IL) as mobile phase additive, desorption solvent, and memory
      effect suppressor in solid-phase microextraction (SPME)-high-performance liquid
      chromatography with fluorescence detection for the determination of six
      heterocyclic aromatic amines have been evaluated for the first time. Several
      chromatographic parameters have been evaluated in the presence or absence of IL
      or using triethylamine as the most common mobile phase additive, with a Nova-Pak
      C18 stationary phase. This IL was found to be clearly superior to triethylamine
      for efficiency as well as peak shape enhancement and sensitivity increase. SPME
      was chosen because it is faster than conventional extraction techniques and
      allowed us to minimize the use of organic solvents. However, memory effect may
      become a problem when a high-sensitivity detector is used. The appropriate
      conditions for the desorption step and to eliminate the memory effect involving
      BMIm-BF(4) were established and optimized. The method was applied for the
      determination of these compounds in commercial meat extracts.

PMID- 19104778
TI  - Antibody orientation enhanced by selective polymer-protein noncovalent
      interactions.
AB  - A unique interaction has been found between protein G' (a truncated recombinant
      bacterial "alphabet" protein which aligns by noncovalent attachment to the
      antibody stem) and poly(methyl methacrylate), a thermoplastic polymer substrate,
      which can be easily fabricated using high-rate processes. Significantly improved
      orientation efficiency with traditional passive adsorption for this system
      (termed ALYGNSA) has been achieved as compared to the same assay performed on a
      polystyrene substrate with protein G'. Results were consistent with an average
      alignment of 80% of the human immunoglobulin G capture antibody which translated
      into a 30% to 50% improved alignment over an array of industry standards tested.
      Laser scanning confocal microscopy confirmed the immunological results. Studies
      of additional poly(methyl methacrylate) polymer derivatives and protein biolinker
      (A and AG) combinations have been conducted and have revealed different degrees
      of antibody alignment. These findings may lead to additional novel noncovalent
      methods of antibody orientation and greater sensitivity in immunological assays.

PMID- 19104776
TI  - Running wheel activity is sensitive to acute treatment with selective inhibitors
      for either serotonin or norepinephrine reuptake.
AB  - RATIONALE: Most antidepressants (AD) directly or indirectly enhance the
      serotonergic tone in the CNS. Since the serotonin system is involved in both, the
      modulation of mood and motor behavior, it was reasoned that these drugs might
      also interfere with running wheel activity (RWA), a form of positively motivated
      motor behavior, which might be linked to pathological states like obsessive
      compulsive disorder (OCD). OBJECTIVES: We used RWA to characterize ADs from all
      major classes. Effects on RWA were compared to effects on general locomotor
      activity (LOC) to control for unspecific effects on general locomotion. METHODS:
      Two hours before lights-off, mice were treated with either vehicle or one of the
      following AD: the selective serotonin reuptake inhibitors (SSRIs) citalopram (3
      10 mg/kg), paroxetine (1-10 mg/kg) and fluoxetine (2-6.6 mg/kg), the selective
      norepinephrine reuptake inhibitor (SNRI) reboxetine (1-10 mg/kg), the monoamine
      oxidase (MAO) inhibitors tranylcypromine (1-3 mg/kg) and moclobemide (3-10
      mg/kg), and the tricyclic ADs desipramine and imipramine (10-30 mg/kg, each). LOC
      and RWA were measured after lights-off. RESULTS: At the highest dose tested, all
      ADs, with the exception of the MAO inhibitors, significantly reduced RWA. Both
      tricyclics inhibited RWA only at doses that similarly affected LOC. In contrast,
      all SSRI and reboxetine inhibited RWA at doses that left LOC unaffected.
      CONCLUSIONS: SSRI and the SNRI reboxetine inhibit RWA at doses not suppressing
      LOC. RWA may represent a simple behavioral readout of positively motivated
      behavior that merits further attention for psychopharmacology.

PMID- 19104779
TI  - Ultrasensitive method for the determination of 4-hydroxy-1-(3-pyridyl)-1-butanone
      releasing DNA adducts by gas chromatography-high resolution mass spectrometry in
      mucosal biopsies of the lower esophagus.
AB  - 4-Hydroxy-1-(3-pyridyl)-1-butanone (HPB)-releasing DNA adducts are formed by
      metabolic activation of the tobacco-specific nitrosamines 4-(methylnitrosamino)-1
      (3-pyridyl)-1-butanone (NNK) and N'-nitrosonornicotine (NNN). NNK and NNN are
      considered carcinogenic to humans by the International Agency for Research on
      Cancer. Existing analytical methods for determination of HPB-releasing DNA
      adducts require 0.3-2.0 g of human target tissues such as lung and esophagus. For
      adduct determination in milligram amounts of biopsy samples, an ultrasensitive
      and specific method is presented using capillary gas chromatography coupled to a
      high-resolution mass spectrometer operated in the negative chemical ionization
      mode (GC-NCI-HRMS). The method has a limit of detection of 4.6 fmol HPB, a limit
      of quantification of 14.9 fmol HBP and a recovery of 45 +/- 15%. Intra- and inter
      day imprecision for N = 6 samples were calculated with coefficients of variation
      of <3.1%. Method applicability was evaluated with biopsies of esophageal mucosa
      (N = 14) yielding 5.6 +/- 1.9 mg tissue and a mean adduct level of 6.13 +/- 9.35
      pmol HPB/mg DNA.

PMID- 19104780
TI  - Elution behavior of poly(lactide-co-succinimide) copolymers studied by SEC-MALS.
AB  - We synthesized poly(lactide-co-succinimide) (PLS) copolymers with the ratio of
      lactide to succinimide units of 3:1 and 6.5:1 and studied their elution behavior
      by size exclusion chromatography with an on-line light-scattering detection.
      Since the copolymers contain a certain amount of carboxyl groups, they behave as
      ionomers in N,N-dimethylacetamide (DMAc) and show a typical polyelectrolyte (PE)
      effect. The PE effect was eliminated by the addition of simple electrolyte like
      LiBr, H(3)PO(4), or both in DMAc. The efficiency of the additive decreases in the
      order: LiBr > LiBr + H(3)PO(4) > H(3)PO(4). The ionic strength of the 0.1 M
      LiBr/DMAc was high enough for the onset of hydrophobic interactions of PLS lactic
      acid segments intermolecularly as well as with the column packing material. The
      drawback of the LiBr + H(3)PO(4)/DMAc solvent system is a rather high intensity
      of the system peaks, which are imposed on the right side of the copolymer signal.
      System peaks strongly influence the determination of number and to a lesser
      extent the weight average molar masses of PLS copolymers. An addition of only
      H(3)PO(4) in high enough concentration to DMAc (0.05 and 0.1 M) successfully
      eliminated the PE effect of the 6.5:1 PLS copolymer. On the contrary, the PE
      effect of the 3:1 PLS copolymer having higher charge density compared to 6.5:1
      PLS copolymer cannot be entirely canceled out in any of the H(3)PO(4)/DMAc
      solutions examined.

PMID- 19104781
TI  - Multiple endonucleases improve MALDI-MS signature digestion product detection of
      bacterial transfer RNAs.
AB  - Individual transfer ribonucleic acids (tRNAs) in a complex mixture can be
      identified by the matrix-assisted laser desorption/ionization mass spectrometry
      (MALDI-MS) detection of their signature digestion products. Signature digestion
      products are endonuclease digestion products whose mass-to-charge value is unique
      thus corresponding to only a single tRNA. To improve the effectiveness of this
      approach, we have expanded the applicable endonucleases and examined the use of
      multiple endonucleases for tRNA identification. The purine specific endonucleases
      RNase T1 and RNase TA generate the largest number of predicted signature
      digestion products. Experimentally, MALDI-MS analysis of endonuclease digests
      from Escherichia coli and Bacillus subtilis finds that any two endonucleases used
      in combination increases tRNA identification by about 25% over the number
      identified with a single endonuclease. Using three endonucleases, RNase T1, RNase
      A, and RNase TA, further improves the number of tRNAs identified by 10-15% over
      those found with two endonucleases. Limitations in the MALDI-MS approach for
      complex mixtures were revealed in this study, suggesting that the direct MALDI-MS
      analysis of signature digestion products is more effective for organisms having
      30 or less unique tRNAs.

PMID- 19104782
TI  - Inflammation markers in point-of-care testing (POCT).
AB  - Inflammation is a central issue in medicine. Inflammatory processes may be local
      or systemic, acute or chronic, and they may be benign or fatal. In bacterial or
      viral infections fast and reliable diagnosis is essential for appropriate
      treatment, e.g. antimicrobial therapy. The time to diagnosis is critical because
      uncontrolled infections may lead to sepsis with a mortality rate close to 50%.
      Beside clinical signs, laboratory markers are important in detecting,
      differentiating, and monitoring inflammation, particularly acute infections.
      Currently several inflammation markers including leukocyte count and leukocyte
      differentiation, C-reactive protein (CRP), procalcitonin (PCT), and interleukins
      (IL) 6 and 8, is available, and potential future serum markers are under
      development. In this article the clinical use of these markers in routine
      laboratory and in point-of-care testing is described and the diagnostic value of
      the four groups of laboratory marker is compared. Current data show that
      leukocyte count or, better, neutrophil count, CRP, and PCT are well suited to
      support of rapid diagnosis of inflammation and infections in children and adults
      whereas measurement of IL-6 and 8 are preferable for detection of sepsis in
      neonates.

PMID- 19104783
TI  - Label-free detection of DNA mutations by SPR: application to the early detection
      of inherited breast cancer.
AB  - A screening analysis of DNA hybridization and the presence of DNA mutations using
      an surface plasmon resonance (SPR) biosensor is shown. The influence of lateral
      and vertical spacers, as well as several hybridization conditions, was studied to
      optimize the differentiation between fully complementary and mismatched DNA
      strands. Our results demonstrated that SPR biosensors were able to detect
      mismatch sequences related to inherited breast cancer, with high specificity and
      sensitivity. Using PCR synthetic sequences as targets, mutant sequences were
      clearly discriminated from fully complementary ones, and detection limits below
      50 nM were achieved.

PMID- 19104785
TI  - Development of a creatinine enzyme-based bar-code-style lateral-flow assay.
AB  - A lateral-flow, enzyme-based, bar-code assay for creatinine employing the concept
      of combination of diffusion and kinetics controlled has been developed. Unlike
      the traditional bar-code version of immunochromatographic assay, which depends on
      the stepwise capture of colorimetric tracer-labeled antibody-antigen complex by
      the immobilized antibody on each successive line, the principle of our proposed
      assay is based on the delay in TMB release and its diffusion in combination with
      horseradish peroxidase kinetics. Hydrogen peroxide (H(2)O(2)) produced from
      enzymatic reactions acts as a limiting factor, which controls the rate of
      conversion of TMB to blue color complex. The assay takes advantage of giving
      ladder bar result therefore without the need of any reading device. Depending on
      the amount of enzymes used, the assay can be one (9 min) or two steps (19 min).
      The strip assay semiquantitatively measures creatinine concentrations ranging
      from 0 to 400 microM. Thirty urine samples and thirty serum samples were tested,
      and the assay showed 90.0% and 86.7% agreement compared with conventional Jaffe
      method, respectively. This assay provides a tool for quick identification of
      creatinine for patients without the requirement of any instrument.

PMID- 19104786
TI  - Study on an on-line molecularly imprinted solid-phase extraction coupled to high
      performance liquid chromatography for separation and determination of trace
      estrone in environment.
AB  - Estrone is one of the important potential endocrine-disrupting compounds, and the
      sensitive and reliable analytical methods for the determination of estrone are
      required for the assurance of human health. In this paper, using estrone as
      template molecule, 3-aminopropyltriethoxysilane as function monomer, and
      tetraethoxysilicane as cross-linker, a highly selective molecularly imprinted
      microsphere was synthesized by surface molecular imprinting technique combined
      with a sol-gel process. The imprinted material was characterized by the Fourier
      transform infrared and static adsorption experiments, and the results showed that
      it exhibited good recognition and selective ability for estrone. A novel method
      for separation and determination of trace estrone in environmental sample was
      developed using on-line molecularly imprinted solid-phase extraction coupled to
      high-performance liquid chromatography. With a sample loading flow rate of 2.6 mL
      min(-1) for a 9.6-min extraction, the enrichment factor obtained by the slopes of
      the linear portion in comparison with the direct injection of 10 microL standard
      sample solution was 1,045. The detection limit (S/N = 3) was 5.7 ng L(-1), and
      the relative standard deviations for nine replicate extractions of 5.0 microg L(
      1) estrone was less than 10.0%. This method was evaluated for quantitative
      determination of estrone in well and lake water samples spiked at two levels (0.5
      and 1.0 microg L(-1)) with recoveries ranging from 86% to 95%.

PMID- 19104787
TI  - The serial reaction time task revisited: a study on motor sequence learning with
      an arm-reaching task.
AB  - With a series of novel arm-reaching tasks, we have shown that visuomotor sequence
      learning encompasses the acquisition of the order of sequence elements, and the
      ability to combine them in a single, skilled behavior. The first component, which
      is mostly declarative, is reflected by changes in movement onset time (OT); the
      second, which occurs without subject's awareness, is measured by changes in
      kinematic variables, including movement time (MT). Key-press-based serial
      reaction time tasks (SRTT) have been used to investigate sequence learning and
      results interpreted as indicative of the implicit acquisition of the sequence
      order. One limitation to SRT studies, however, is that only one measure is used,
      the response time, the sum of OT and MT: this makes interpretation of which
      component is learnt difficult and disambiguation of implicit and explicit
      processes problematic. Here, we used an arm-reaching version of SRTT to propose a
      novel interpretation of such results. The pattern of response time changes we
      obtained was similar to the key-press-based tasks. However, there were
      significant differences between OT and MT, suggesting that both partial learning
      of the sequence order and skill improvement took place. Further analyses
      indicated that the learning of the sequence order might not occur without
      subjects' awareness.

PMID- 19104788
TI  - Task-specific increase in corticomotor excitability during tactile
      discrimination.
AB  - Task-dependant changes in corticomotor excitability have been described mainly in
      the context of grasp-oriented actions, neglecting the sensory aspects of hand
      function. Here, we contrasted task-dependant facilitation in small hand muscles
      [i.e., first dorsal interosseous (FDI) and abductor digiti minimi (ADM)] in the
      context of finger movements involving either discrimination or non discrimination
      (ND) of tactile features. Healthy young individuals (n = 16) were trained to
      produce rhythmic to and fro movements at the sound of metronome ticks (0.8 Hz
      frequency, 5 s total duration) with either the index or the little finger of the
      right hand. In the tactile discrimination (TD) condition, participants were asked
      to attend to the location of two different 2-D tactile shapes disposed on the
      explored surface, whereas in the ND condition, the finger was moved over a blank
      surface. In both conditions, a transcranial magnetic stimulation (TMS) pulse was
      delivered at a specific time point in the course of the finger movement.
      Corticomotor excitability was assessed by monitoring changes in the amplitude and
      latency of motor evoked potentials (MEPs) in the FDI and ADM. Changes in the
      duration of the silent period were also assessed. The analysis revealed a
      significant large effect of task conditions (P < 0.001) on MEP amplitude, owing
      to the increase in MEP size observed during the TD, as compared to the ND
      condition. No interaction between "Task" and "Muscle" was detected, however,
      indicating that MEPs in the two muscles were equally affected by the task
      conditions. No significant changes were detected for variations in MEP latency or
      in the SP duration. An additional control experiment performed in a subset of the
      participants (n = 9) showed that MEP facilitation was substantially reduced when
      attention to sensations arising from finger contact with the shapes was diverted
      away by completion of a concurrent cognitive task (counting backward by three).
      These findings provide further insights into the factors influencing task
      dependant changes in corticomotor excitability during hand actions. Our results
      highlight the importance of behavioral context and attention, in particular, in
      leading to further enhancement in corticomotor excitability when the finger is
      actively engaged in TD.

PMID- 19104789
TI  - eNOS T-786C polymorphism affects atorvastatin-induced changes in erythrocyte
      membrane fluidity.
AB  - PURPOSE: Statins have pleiotropic effects, including endothelial nitric oxide
      synthase (eNOS) upregulation and increased nitric oxide formation, which can be
      modulated by a genetic polymorphism in the promoter region of the eNOS gene (T
      786C). Here, we report our investigation of whether this polymorphism modulates
      the effects of atorvastatin on the fluidity of erythrocyte membranes. METHODS: We
      genotyped 200 healthy subjects (males, 18-60 years of age) and then randomly
      selected 15 of these with the TT genotype and 15 with the CC genotype to receive
      placebo or atorvastatin (10 mg/day oral administration) for 14 days. Cell
      membrane fluidity was evaluated by electron paramagnetic resonance (EPR) and spin
      labeling method. The EPR spectra were registered on a VARIAN-E4 spectrometer.
      Thiobarbituric acid-reactive species (TBA-RS) and plasma membrane cholesterol
      were determined in the erythrocytes. RESULTS: Atorvastatin reduced membrane
      fluidity in CC subjects (P < 0.05) but not in those with the TT genotype (P >
      0.05). While no significant differences were found in plasma membrane cholesterol
      concentrations, higher TBA-RS concentrations were found in the CC subjects than
      in the TT subjects (P < 0.05). CONCLUSIONS: These findings suggest that a short
      treatment with atorvastatin is disadvantageous to subjects with the CC genotype
      for the T-786C polymorphism compared to those with TT genotype, at least in terms
      of the hemorheological properties of erythrocytes.

PMID- 19104790
TI  - An analysis of the clinical development of drugs in Norway for the year 2000: the
      completion of research and publication of results.
AB  - OBJECTIVE: In Norway, very little data are available on the relation between the
      total number of research projects on the clinical development of drugs that have
      been started, the number of these projects in which the research phase has been
      completed and the number of projects for which results have been published. The
      aim of this study was to determine the number of projects in which the research
      phase had been completed and the results published. MATERIAL AND METHODS:
      Information on research projects carried out on the clinical development of drugs
      during the year 2000 was obtained from the archives of the Norwegian Research
      Ethical Committee (REC) and subsequently analysed. RESULTS: The final analysis
      revealed that 245 research projects on the clinical development of drugs had been
      started in 2000. Of these, 178 (73%) completed the research phase as planned. The
      results of 131 (54%) of these projects were published in a scientific journal,
      and another 34 (14%) were reported as a congress abstract or as report to a
      sponsor; 80 (33%) were not published at all. Industrial sponsors seemed to
      promote both the completion of the research process and the publication of
      results in scientific journals.

PMID- 19104791
TI  - Clinical pharmacokinetics of aminoglycosides in the neonate: a review.
AB  - BACKGROUND: Sepsis is common in neonates and is a major cause of morbidity and
      mortality. Sixty percent of preterm neonates receive at least one antibiotic, and
      43% of the antibiotics administered to these neonates are aminoglycosides. The
      clearance (Cl), serum half-life (t(1/2)), and volume of distribution (Vd) of
      aminoglycosides change during the neonatal life, and the pharmacokinetics of
      aminoglycosides need to be studied in neonates in order to optimise therapy with
      these drugs. OBJECTIVE: The aim of this work is to review the published data on
      the pharmacokinetics of aminoglycosides in order to provide a critical analysis
      of the literature that can be a useful tool in the hands of physicians. METHODS:
      The bibliographic search was performed electronically using PubMed, as the search
      engine, through July 11th, 2008. Firstly, a Medline search was performed with the
      keywords "pharmacokinetics of aminoglycosides in neonates" with the limit of
      "human". Other Medline searches were performed with the keywords
      "pharmacokinetics of ... in neonates" followed by the name of the
      aminoglycosides: amikacin, gentamicin, netilmicin and tobramycin. In addition,
      the book Neofax: A Manual of Drugs Used in Neonatal Care by Young and Mangum
      (Thomson Healthcare, 2007) was consulted. RESULTS: The aminoglycosides are mainly
      eliminated by the kidney, and their elimination rates are reduced at birth. As a
      consequence Cl is reduced and t(1/2) is prolonged in the neonate as compared to
      more mature infants. The high body-water content of the neonate results in a
      large Vd of aminoglycosides as these drugs are fairly water soluble. Postnatal
      development is an important factor in the maturation of the neonate, and as
      postnatal age proceeds, Cl of aminoglycosides increases. CONCLUSION: The
      maturation of the kidney governs the pharmacokinetics of aminoglycosides in the
      infant. Cl and t(1/2) are influenced by development, and this must be taken into
      consideration when planning a dosage regimen with aminoglycosides in the neonate.
      Aminoglycosides are fairly water soluble, and the larger water content of
      neonates yields a larger Vd in these patients.

PMID- 19104792
TI  - Basal cerebral venous drainage from cavernous sinus dural arteriovenous fistulas.
AB  - INTRODUCTION: This study aimed to define the patterns of basal cerebral venous
      drainage (BCVD) from cavernous sinus dural arteriovenous fistulas (CSDAVFs).
      MATERIALS AND METHODS: Forty sets of selective angiographic data from 36 patients
      with spontaneous CSDAVFs (age range, 53-79 years) were retrospectively analyzed
      for their drainage patterns. Three types of BCVD were observed, i.e.,
      superolateral type, BCVD via the deep middle cerebral vein or uncal vein;
      posterolateral type, BCVD via the superior petrosal sinus and petrosal vein; and
      posteromedial type, BCVD via the bridging vein and the anterior
      pontomesencephalic vein. MR images and/or 3D-DSA images were also reviewed when
      available. RESULTS: BCVD from CSDAVF was found in 12 patients (30%), and the
      other drainage routes included the superior ophthalmic vein in 25 (63%), the
      inferior petrosal sinus in 17 (43%), the superficial middle cerebral vein in 17
      (43%), intercavernous sinus in 15 (38%), the superior petrosal sinus in seven
      (18%), and pterygoid plexus in two (5%), respectively. In 12 patients with BCVD,
      superolateral type was found in four (33%), posterolateral type in five (42%),
      and posteromedial type in seven (58%). Four cases of posteromedial type were
      associated with other types of BCVD. CONCLUSION: CSDAVFs are often associated
      with BCVD via three different pathways. The posteromedial type via the bridging
      vein is the most frequent type of BCVD.

PMID- 19104793
TI  - Hyperperfusion syndrome after carotid stent angioplasty.
AB  - INTRODUCTION: This study assesses the incidence and causes of hyperperfusion
      syndrome occurring after carotid artery stenting (CAS). MATERIALS AND METHODS: We
      retrospectively reviewed the clinical database of 417 consecutive patients who
      were treated with CAS in our department to identify patients who developed
      hyperperfusion syndrome and/or intracranial hemorrhage. Magnetic resonance
      imaging (MRI) including fluid-attenuated inversion recovery and diffusion
      weighted imaging was performed before and after CAS in 269 cases. A Spearman's
      rho nonparametric correlation was performed to determine whether there was a
      correlation between the occurrence/development of hyperperfusion syndrome and the
      patient's age, degree of stenosis on the stented and contralateral side, risk
      factors such as diabetes, smoking, hypertension, adiposity, gender and
      fluoroscopy time, and mean area of postprocedural lesions as well as preexisting
      lesions. Significance was established at p < 0.05. RESULTS: Of the 417 carotid
      arteries stented and where MRI was also completed, we found hyperperfusion
      syndrome in 2.4% (ten cases). Patients who had preexisting brain lesions
      (previous or acute stroke) were at a higher risk of developing hyperperfusion
      syndrome (p = 0.022; Spearman's rho test). We could not validate any correlation
      with the other patient characteristics. CONCLUSION: Extensive microvascular
      disease may be a predictor of hyperperfusion syndrome after carotid stent
      placement. We believe that further studies are warranted to predict more
      accurately which patients are at greater risk of developing this often fatal
      complication.

PMID- 19104794
TI  - MR imaging findings of retinal hemorrhage in a case of nonaccidental trauma.
AB  - Retinal hemorrhage is a well-recognized manifestation of child abuse found in
      many babies with shaken baby syndrome. The presence of retinal hemorrhage is
      generally associated with more severe neurological damage and a worse clinical
      outcome. MR imaging findings of retinal hemorrhages are not well described in the
      pediatric literature. We present a 6-month-old boy with new-onset seizures,
      subdural hemorrhage and bilateral retinal hemorrhages that were detected by MRI
      and confirmed by indirect ophthalmoscopy. This case demonstrates the MR imaging
      findings of retinal hemorrhages and the importance of radiologists being able to
      recognize these specific imaging features.

PMID- 19104795
TI  - Infantile osteopetrosis on head CT.

PMID- 19104796
TI  - Method for performing cerebral perfusion-weighted MRI in neonates.
AB  - Cerebral perfusion-weighted imaging (PWI) in neonates is known to be technically
      difficult and there are very few published studies on its use in preterm infants.
      In this paper, we describe one convenient method to perform PWI in neonates, a
      method only recently used in newborns. A device was used to manually inject
      gadolinium contrast material intravenously in an easy, quick and reproducible
      way. We studied 28 newborn infants, with various gestational ages and weights,
      including both normal infants and those suffering from different brain
      pathologies. A signal intensity-time curve was obtained for each infant, allowing
      us to build perfusion maps. This technique offered a fast and easy method to
      manually inject a bolus gadolinium contrast material, which is essential in
      performing PWI in neonates. Cerebral PWI is technically feasible and reproducible
      in neonates of various gestational age and with various pathologies.

PMID- 19104797
TI  - Evolutionary history of an MHC gene in two leporid species: characterisation of
      Mhc-DQA in the European brown hare and comparison with the European rabbit.
AB  - We surveyed the genetic diversity of the expressed major histocompatibility
      complex class II DQA locus in natural populations of European brown hares, Lepus
      europaeus, from Austria and Belgium (267 individuals in total). Based on cDNA
      sequences, we designed hare-specific primers to amplify the highly variable
      second exon of the DQA gene. Using cloning-sequencing methodology and capillary
      electrophoresis single-strand conformation polymorphism, we found ten alleles of
      the DQA exon 2 locus across these two European regions, of which eight are
      described for the first time. To search for signals of selection and
      recombination in the evolution of the DQA gene within the leporids, we augmented
      our sample with orthologous DQA alleles from the European rabbit, Oryctolagus
      cuniculus, in order to carry out a species level, species pairwise comparison. We
      found evidence of recombination in the history of the DQA sequences in leporids
      with some recombinant alleles bridging the species divide. In both species,
      selection on peptide binding site codons can be detected, though stronger for the
      rabbit. This result suggests that there may be a differential selection pressure
      in the deeper evolutionary history of these two species due to differences in
      several demographic and ecological traits likely subjecting them to differential
      selection by parasites. Finally, evolutionary relationships show a widespread and
      statistically significant intermingling of alleles from the two species. The many
      macroparasites shared between hares and rabbits may explain this pattern of trans
      species polymorphism.

PMID- 19104799
TI  - Healthcare costs for new technologies.
AB  - INTRODUCTION: Continuous ageing of the population coupled with growing health
      consciousness and continuous technological advances have fueled the rapid rise in
      healthcare costs in the United States and Europe for the past several decades.
      The exact impact of new medical technology on long-term spending growth remains
      the subject of controversy. By all measures it is apparent that new medical
      technology is the dominant driver of increases in health-care costs and hence
      insurance premiums. OBJECTIVE: This paper addresses the impact of medical
      technology on healthcare delivery systems with regard to medical practice and
      costs. We first explore factors affecting the growth of medical technology and
      then attempt to provide a means for assessing the effectiveness of medical
      technology. DISCUSSION: Avoidable healthcare cost drivers are identified and
      related policy issues are discussed.

PMID- 19104798
TI  - PET and MRI in cardiac imaging: from validation studies to integrated
      applications.
AB  - INTRODUCTION: Positron emission tomography (PET) is the gold standard for non
      invasive assessment of myocardial viability and allows accurate detection of
      coronary artery disease by assessment of myocardial perfusion. Magnetic resonance
      imaging (MRI) provides high resolution anatomical images that allow accurate
      evaluation of ventricular structure and function together with detection of
      myocardial infarction. OBJECTIVE: Potential hybrid PET/MR tomography may
      potentially facilitate the combination of information from these imaging
      modalities in cardiology. Furthermore, the combination of anatomical MRI images
      with the high sensitivity of PET for detecting molecular targets may extent the
      application of these modalities to the characterization of atherosclerotic
      plaques and to the evaluation of angiogenetic or stem cell therapies, for
      example. DISCUSSION: This article reviews studies using MRI and PET in parallel
      to compare their performance in cardiac applications together with the potential
      benefits and applications provided by hybrid PET/MRI systems.

PMID- 19104800
TI  - PET/MRI: a different spin from under the rim.
AB  - INTRODUCTION: Hybrid imaging is now widely accepted in cancer imaging with
      increasing use of PET/CT in clinical practice. The advantages of MRI compared to
      CT with respect to radiation exposure and soft-tissue lesion contrast, as well as
      the possibility of performing more sophisticated assessment of tissue chemistry,
      have stimulated interest in the development of hybrid PET/MR imaging systems.
      OBJECTIVE: While PET/CT simultaneously increases diagnostic quality and patient
      throughput compared to PET, offsetting the higher cost of this instrumentation,
      PET/MRI will likely be more expensive again and is currently unlikely to be
      competitive in terms of throughput. DISCUSSION: To realize the unique potential
      advantages of combined PET/MRI, we believe that PET/MRI devices should be
      designed to be a complementary tool running in parallel with PET/CT. The use of
      PET/CT for whole-body screening could identify lesions requiring more detailed
      anatomical and biological characterization. Selection of only those patients and
      those lesions for which this information is critical for treatment selection and
      planning will provide efficient and easily justified use of what will, for the
      foreseeable future, be an expensive and limited resource.

PMID- 19104801
TI  - The potential of PET/MR for brain imaging.
AB  - INTRODUCTION: The completion of an integrated PET/MR prototype system for brain
      imaging is the latest step in the evolution of positron emission tomography.
      Early images with this new imaging system demonstrate that high-resolution
      multiparametric studies can be combined without significant loss of performance
      of either imaging modality. OBJECTIVE: This new technology will make fusion of
      morphological and biological information much easier, yield real-time assessment
      of complementary variables and will provide dynamic information for kinetic
      modelling. Simultaneous acquisition of various metabolic and functional
      parameters may open new insights into the organization of the brain and its
      changes in disease. DISCUSSION: A new field may open up for molecular and
      cellular imaging, where new targets--e.g. angiogenesis, gene transfer, function
      and migration of transplanted cells--can be imaged in the morphological context
      and within a functional environment. This application might have a special impact
      on the translation of treatment concepts from experimental models into clinical
      application. If the added value of the hybrid system for diagnosis and treatment
      monitoring is established, a cost-effective PET/MR combination might attain wider
      clinical application.

PMID- 19104802
TI  - Combined PET/MRI: a new dimension in whole-body oncology imaging?
AB  - INTRODUCTION: Hybrid imaging systems providing morphological and functional data
      in a single session have been available for oncological imaging for some time. So
      far, computed tomography (CT) has been the morphological method-of-choice for
      inclusion into these hybrid imaging systems. However, recently, research has
      focused on hardware-based fusion of function with magnetic resonance imaging
      (MRI) rather than CT. OBJECTIVES: Now that the first head-only positron emission
      tomography (PET)/MRI systems have been installed and whole-body systems are to be
      expected in the near future, potential indications in clinical oncology have to
      be addressed. DISCUSSION: This article discusses potential indications of PET/MRI
      in whole-body oncology imaging. Potential advantages and disadvantages compared
      with currently available hybrid imaging systems will be reviewed.

PMID- 19104804
TI  - A look ahead: PET/MR versus PET/CT.
AB  - INTRODUCTION: Integration of positron emission tomography (PET) and magnetic
      resonance (MR) has become a topic of increasing interest to the imaging community
      over the past two years. OBJECTIVES: In this text, the authors attempt to
      distinguish facts from fiction concerning such integrated systems. Analysis of
      existing information of combined imaging on existing brain PET/MR systems and
      imaging experience with PET-computed tomography (CT) is reviewed. Various types
      of system integration of PET and MR are discussed with completely independent
      systems on one hand and completely integrated systems with the possibility of
      simultaneous data acquisition on the other hand. Furthermore, it is discussed,
      what simultaneous data acquisition with nuclear imaging systems combined with MR
      or CT really means, as technical simultaneity may not be relevant in light of the
      pharmacokinetics of the nuclear tracers used. DISCUSSION: The authors conclude
      that combining PET/MR is an interesting research endeavor with uncertain outcome.
      They argue that, while completely simultaneous brain applications are of research
      interest immediately, clinical applications do not currently warrant the
      construction of fully integrated systems. Systems adjacent to each other, where
      imaging tables are linked with a patient "shuttle" thereby requiring only patient
      translation but no repositioning, may be a good start to assess the value of
      integrated PET/MR.

PMID- 19104803
TI  - Multimodality image registration with software: state-of-the-art.
AB  - INTRODUCTION: Multimodality image integration of functional and anatomical data
      can be performed by means of dedicated hybrid imaging systems or by software
      image co-registration techniques. Hybrid positron emission tomography
      (PET)/computed tomography (CT) systems have found wide acceptance in oncological
      imaging, while software registration techniques have a significant role in
      patient-specific, cost-effective, and radiation dose-effective application of
      integrated imaging. OBJECTIVES: Software techniques allow accurate (2-3 mm) rigid
      image registration of brain PET with CT and MRI. Nonlinear techniques are used in
      whole-body image registration, and recent developments allow for significantly
      accelerated computing times. Nonlinear software registration of PET with CT or
      MRI is required for multimodality radiation planning. Difficulties remain in the
      validation of nonlinear registration of soft tissue organs. The utilization of
      software-based multimodality image integration in a clinical environment is
      sometimes hindered by the lack of appropriate picture archiving and communication
      systems (PACS) infrastructure needed to efficiently and automatically integrate
      all available images into one common database. DISCUSSION: In cardiology
      applications, multimodality PET/single photon emission computed tomography and
      coronary CT angiography imaging is typically not required unless the results of
      one of the tests are equivocal. Software image registration is likely to be used
      in a complementary fashion with hybrid PET/CT or PET/magnetic resonance imaging
      systems. Software registration of stand-alone scans "paved the way" for the
      clinical application of hybrid scanners, demonstrating practical benefits of
      image integration before the hybrid dual-modality devices were available.

PMID- 19104805
TI  - Magnetic resonance imaging methodology.
AB  - INTRODUCTION: Magnetic resonance (MR) methods are non-invasive techniques to
      provide detailed, multi-parametric information on human anatomy, function and
      metabolism. Sensitivity, specificity, spatial and temporal resolution may,
      however, vary depending on hardware (e.g., field strength, gradient strength and
      speed) and software (optimised measurement protocols and parameters for the
      various techniques). Furthermore, multi-modality imaging may enhance specificity
      to better characterise complex disease patterns. OBJECTIVE: Positron emission
      tomography (PET) is an interesting, largely complementary modality, which might
      be combined with MR. Despite obvious advantages, combining these rather different
      physical methods may also pose challenging problems. At this early stage, it
      seems that PET quality may be preserved in the magnetic field and, if an adequate
      detector material is used for the PET, MR sensitivity should not be significantly
      degraded. Again, this may vary for the different MR techniques, whereby
      functional and metabolic MR is more susceptible than standard anatomical imaging.
      DISCUSSION: Here we provide a short introduction to MR basics and MR techniques,
      also discussing advantages, artefacts and problems when MR hardware and PET
      detectors are combined. In addition to references for more detailed descriptions
      of MR fundamentals and applications, we provide an early outlook on this novel
      and exciting multi-modality approach to PET/MR.

PMID- 19104806
TI  - Risks and safety aspects related to PET/MR examinations.
AB  - INTRODUCTION: The introduction of positron emission tomography (PET)/magnetic
      resonance (MR) systems into medical practice in the foreseeable future may not
      only lead to a gain in clinical diagnosis compared to PET/computed tomography
      (CT) imaging due to the superior soft-tissue contrast of the MR technology but
      can also substantially reduce exposure of patients to ionizing radiation. On the
      other hand, there are also risks and health effects associated with the use of
      diagnostic MR devices that have to be considered carefully. OBJECTIVES: This
      review article summarizes biophysical and biological aspects, which are of
      relevance for the assessment of health effects related to the exposure of
      patients to both ionizing radiation in PET and magnetic and electromagnetic
      fields in MR. On this basis, some considerations concerning the justification and
      optimization of PET/MR examinations are presented--as far as this is possible at
      this very early stage. DISCUSSION: Current safety standards do not take into
      account synergistic effects of ionizing radiation and magnetic and
      electromagnetic fields. In the light of the developing PET/MR technology, there
      is an urgent need to investigate this aspect in more detail for exposure levels
      that will occur at PET/MR systems.

PMID- 19104807
TI  - A decade of combined imaging: from a PET attached to a CT to a PET inside an MR.

PMID- 19104808
TI  - Multimodality imaging: an update on PET/CT technology.
AB  - INTRODUCTION: Since their introduction in 2001, PET/CT systems have gained wide
      acceptance primarily due to their inherent ability to combine functional and
      structural information about the underlying disease state of the patient in a
      single imaging session. Their significance has also been documented with regard
      to their short imaging times, which minimize patient anxiety and image blurring
      due to patient motion. In the past seven years, PET/CT systems have replaced
      dedicated PET systems as the imaging modality of choice for diagnostic evaluation
      of oncology patients. OBJECTIVES: The purpose of this article is to review the
      evolution of PET/CT systems and document their current status. DISCUSSION: Recent
      improvements in instrumentation are highlighted together with some outstanding
      issues that arise for specific PET/CT applications. These are followed by a
      description of some of the more common clinical applications of PET/CT imaging
      such as staging malignant disease, treatment planning, and monitoring therapy
      response. Finally, the future developments of PET/CT systems with regard to
      sensitivity, resolution, and new radiopharmaceuticals are discussed. The article
      concludes by presenting some issues concerning the next stage in the future of
      PET imaging, namely PET/MRI.

PMID- 19104809
TI  - PET/MRI system design.
AB  - INTRODUCTION: The combination of clinical MRI and PET systems has received
      increased attention in recent years. In contrast to currently used PET/CT
      systems, PET/MRI offers not only improved soft-tissue contrast and reduced levels
      of ionizing radiation, but also a wealth of MRI-specific information such as
      functional, spectroscopic and diffusion tensor imaging. Combining PET and MRI,
      however, has proven to be very challenging, due to the detrimental cross-talk
      effects between the two systems. OBJECTIVE: Significant progress has been made in
      the recent years to overcome these difficulties, with several groups reporting
      PET/MRI prototypes for animal imaging and a clinical insert for neurological
      applications being demonstrated at the 2007 Annual Meeting of the Society of
      Nuclear Medicine. DISCUSSION: In this paper we review different architectures for
      clinical PET/MRI systems, and their possibilities, limitations and technological
      obstacles.

PMID- 19104810
TI  - Towards quantitative PET/MRI: a review of MR-based attenuation correction
      techniques.
AB  - INTRODUCTION: Positron emission tomography (PET) is a fully quantitative
      technology for imaging metabolic pathways and dynamic processes in vivo.
      Attenuation correction of raw PET data is a prerequisite for quantification and
      is typically based on separate transmission measurements. In PET/CT attenuation
      correction, however, is performed routinely based on the available CT
      transmission data. OBJECTIVE: Recently, combined PET/magnetic resonance (MR) has
      been proposed as a viable alternative to PET/CT. Current concepts of PET/MRI do
      not include CT-like transmission sources and, therefore, alternative methods of
      PET attenuation correction must be found. This article reviews existing
      approaches to MR-based attenuation correction (MR-AC). Most groups have proposed
      MR-AC algorithms for brain PET studies and more recently also for torso PET/MR
      imaging. Most MR-AC strategies require the use of complementary MR and
      transmission images, or morphology templates generated from transmission images.
      We review and discuss these algorithms and point out challenges for using MR-AC
      in clinical routine. DISCUSSION: MR-AC is work-in-progress with potentially
      promising results from a template-based approach applicable to both brain and
      torso imaging. While efforts are ongoing in making clinically viable MR-AC fully
      automatic, further studies are required to realize the potential benefits of MR
      based motion compensation and partial volume correction of the PET data.

PMID- 19104811
TI  - Tumor specific cytotoxicity of beta-glucosylceramide: structure-cytotoxicity
      relationship and anti-tumor activity in vivo.
AB  - This study describes the structure-cytotoxicity relationship of beta
      glucosylceramide (beta-GluCer) and its antitumor activity in vivo. Unglycosylated
      ceramide had no selective cytotoxicity which demonstrated that the sugar moiety
      plays a critical role for the expression of selective cytotoxicity by beta
      GluCer. beta-Galactosylceramide also showed tumor specific cytotoxicity
      suggesting that the chemical structure of sugar group is not a factor for the
      selective toxicity. Similarly, unglycosylated ceramides of short acyl chain also
      selectively inhibited the growth of cancer cells. These findings in concert point
      to the importance of the hydrophilicity of the ceramide molecule rather than the
      chemical structure for the cyto-selectivity. Treatment of the cells with beta
      GluCer increased the concentration of reactive oxygen species leading to cell
      cycle arrest and necrosis. Intraperitoneal administration of beta-GluCer
      significantly suppressed the growth of tumor implanted to the back of mice. beta
      GluCer also induced antitumor immunity via the activation of NKT cells in vivo,
      and decreased the tumor metastasis of lymphoma cells. The present study thus
      demonstrated the antitumor activity of beta-GluCer in vivo, and discussed the
      mechanisms responsible for the growth inhibition.

PMID- 19104813
TI  - The xc- cystine/glutamate antiporter as a potential therapeutic target for small
      cell lung cancer: use of sulfasalazine.
AB  - PURPOSE: To determine whether the xc- cystine transporter could be a useful
      therapeutic target for small-cell lung cancer (SCLC). METHODS: Human SCLC cell
      cultures were examined for growth dependence on extracellular cystine, xc-
      expression, glutathione levels and response to highly specific xc- inhibitors,
      i.e., monosodium glutamate (MSG) and the anti-inflammatory drug, sulfasalazine
      (SASP). In studying tumor growth inhibition by SASP, use was also made of a novel
      SCLC tissue xenograft model, LU6-SCLC, derived from a chemoresistant patient's
      SCLC specimen. RESULTS: Growth of NCI-H69 and NCI-H82 SCLC cells greatly depended
      on xc- -mediated uptake of cystine. SASP substantially reduced their glutathione
      levels (>70%; 0.3 mM SASP; 24 h) and growth (72 h) with IC(50)s of 0.21 and 0.13
      mM, respectively; MSG also inhibited growth markedly. Both SASP- and MSG-induced
      growth arrests were largely prevented by cystine uptake-enhancing 2
      mercaptoethanol (66 approximately microM) indicating they were primarily due to
      cystine starvation. Without major side-effects, SASP (i.p.) restrained growth of
      NCI-H69 cell xenografts (approximately 50%) and, importantly, substantially
      inhibited growth of the clinically more relevant LU6-SCLC tissue xenografts
      (approximately 70% by stereological analysis), reducing tumor glutathione
      contents. CONCLUSIONS: The xc- cystine/glutamate antiporter is potentially useful
      as a target for therapy of SCLC based on glutathione depletion. Sulfasalazine may
      be readily used for this approach, especially in combination chemotherapy.

PMID- 19104812
TI  - Intra-hepatic arterial administration with miriplatin suspended in an oily
      lymphographic agent inhibits the growth of tumors implanted in rat livers by
      inducing platinum-DNA adducts to form and massive apoptosis.
AB  - BACKGROUND: Miriplatin (formerly SM-11355), a novel lipophilic platinum complex
      developed to treat hepatocellular carcinoma, is administered into the hepatic
      artery using an oily lymphographic agent (Lipiodol Ultra-Fluide) as a carrier. We
      clarified the usefulness of miriplatin as an agent for transarterial
      chemoembolization. METHODS: Platinum compounds released from miriplatin into
      serum, medium and Earle's balanced salt solution were examined. Then, miriplatin
      and cisplatin were administered to rats bearing hepatoma AH109A tumors in livers.
      Platinum concentrations in tissues and DNA were assessed. RESULTS: Miriplatin
      showed a more sustained release than cisplatin. Dichloro[(1R, 2R)-1, 2
      cyclohexane diamine-N, N']platinum, the most abundant platinum compound released
      from miriplatin, was as effective as cisplatin in inhibiting the growth of cells.
      Miriplatin was selectively disposed of in tumors, maintained in tumors longer
      than cisplatin and caused apparent tumor regression inducing platinum-DNA adducts
      to form and massive apoptosis. CONCLUSION: Miriplatin appears to be a suitable
      chemotherapeutic agent for transarterial chemoembolization.

PMID- 19104814
TI  - A phase II trial evaluating capecitabine and irinotecan as second line treatment
      in patients with oesophago-gastric cancer who have progressed on, or within 3
      months of platinum-based chemotherapy.
AB  - RATIONALE: There is no standard second line therapy for relapsed oesophago
      gastric (O-G) cancer. METHODS: We recruited 29 eligible patients with relapsed O
      G cancer who had progressed during or within 3 months of prior chemotherapy to
      assess the efficacy and toxicity of capecitabine [2,000 mg/(m(2) day) on days 1
      14] and irinotecan (250 mg/m(2)) given every 3 weeks. RESULTS: Five patients
      (17%) demonstrated objective response, while a further seven patients (24%)
      achieved disease stabilisation. Median progression-free survival and overall
      survival were 3.1 months (95% CI = 2.2-4.1 months) and 6.5 months (95%CI = 6-7.1
      months), respectively. Among symptomatic patients, palliation of tumour-related
      symptoms included resolution of reflux (5/12 pts), dysphagia (3/9 pts) and weight
      loss (4/9 pts), improvements in anorexia (4/10 pts), nausea (3/4 pts), vomiting
      (4/6 pts) and pain (4/16 pts). Grade 3-4 toxicities were diarrhoea (15%), nausea
      and vomiting (7%), lethargy (31%), neutropenia (31%), anemia (14%) and
      thrombocytopenia (7%). CONCLUSIONS: Capecitabine and irinotecan has anti-tumour
      activity as second line treatment for relapsed O-G cancer, and provides an
      important improvement in disease related symptoms.

PMID- 19104815
TI  - Ciprofloxacin sensitizes hormone-refractory prostate cancer cell lines to
      doxorubicin and docetaxel treatment on a schedule-dependent manner.
AB  - PURPOSE: Combination therapy has generated a significant interest in the clinical
      setting since certain agents, with known mechanisms of action and non-overlapping
      toxicities may increase the therapeutic potential of anticancer drugs by
      decreasing systemic toxicity and overcoming drug resistance. Doxorubicin and
      docetaxel, two standard antineoplastic agents in hormone-refractory prostate
      cancer (HRPC) therapy and ciprofloxacin were evaluated singly and in several
      simultaneous and sequential drug combination schemes, against PC-3 and LNCaP cell
      lines. METHODS: Cellular viability was determined by the resazurin assay and the
      assessment of synergism, additivity or antagonism was carried out by the median
      effect analysis. The importance of dose, exposure time and type of administration
      were investigated and compared. RESULTS: Ciprofloxacin-doxorubicin or docetaxel
      combinations resulted in prominent additive or synergistic effects in both cell
      lines, when the cells were pre-treated with ciprofloxacin. These results suggest
      a rationale for dose reduction of doxorubicin and docetaxel in prostate cancer
      therapy, since the doses needed to achieve 50% cell death may be decreased by
      approximately 4- to 15-fold or 3- to 8-fold, respectively, after a pre-treatment
      with ciprofloxacin. In contrast, the referred combinations yielded moderate
      antagonistic effects when used concurrently in this in vitro system. CONCLUSIONS:
      Ciprofloxacin sensitized HRPC cells to doxorubicin or docetaxel-induced growth
      inhibition and, therefore, may play a role as chemosensitizing agent in prostate
      cancer treatment.

PMID- 19104816
TI  - Non-pegylated liposomal doxorubicin and docetaxel in metastatic breast cancer:
      final results of a phase II trial.
AB  - BACKGROUND: Non-pegylated liposomal doxorubicin (NPLD) has demonstrated
      equivalent antitumor activity to conventional doxorubicin and a significantly
      lower risk of cardiotoxicity when given as single agent or in combination with
      cyclophosphamide, but there is limited experience with the combination of NPLD
      and taxanes. This phase II study was performed to evaluate the efficacy and
      safety of the NPLD and docetaxel in patients with metastatic breast cancer.
      PATIENTS AND METHODS: A total of 51 patients were treated with NPLD (60 mg/m(2))
      and docetaxel (75 mg/m(2)) in 3-weeks intervals for up to eight cycles. RESULTS:
      The overall response rate was 50% and 78% of patients derived a clinical benefit.
      Median time to progression and overall survival were 10.0 months (95% CI, 6.9
      13.1 months) and 25 months (95% CI, 22.1-29.8 months), respectively. Median
      duration of response was 12.0 months (95% CI 7.1-16.9). The treatment was
      generally well tolerated and associated with toxicities that were consistent with
      the known side-effects of the individual agents and of anthracycline/taxane
      combinations. There were no symptomatic cardiac averse events and mild
      asymptomatic LVEF changes were reported in five patients. CONCLUSIONS: The
      combination of NPLD and docetaxel is well tolerated and has high antitumour
      activity in MBC patients.

PMID- 19104817
TI  - Fixed-dose rate infusion of gemcitabine and weekly cisplatin in elderly or poor
      performance status patients with unresectable non-small cell lung cancer.
AB  - PURPOSE: We investigated the efficacy and toxicity of a 4-week schedule of a
      fixed dose rate infusion of gemcitabine and weekly cisplatin in elderly or poor
      performance status patients with unresectable non-small cell lung cancer (NSCLC).
      METHODS: In this study, 48 patients with previously untreated NSCLC were given
      combination chemotherapy that consisted of gemcitabine 1,000 mg/m(2) (10
      mg/m(2)/min fixed dose rate infusion) and cisplatin 25 mg/m(2), and both drugs
      were given weekly on days 1, 8 and 15. RESULTS: A partial response and stable
      disease were observed in 20 patients (41.7%, 95% CI; 27.8-55.6%) and 12 patients
      (25.0%), respectively. The overall median survival was 10.30 months (range: 7.85
      12.74 months). Major toxicities included neutropenia (grade 3 to 4, 29.2%) and
      infection (grade 3 to 4, 27.1%). CONCLUSIONS: Our results indicate that this
      regimen is a feasible treatment for elderly or poor performance status patients
      with unresectable NSCLC. Nevertheless, the morbidity due to myelosuppression and
      infection following this treatment should be carefully considered.

PMID- 19104820
TI  - Predictors of bone density testing in patients with rheumatoid arthritis.
AB  - Patients with rheumatoid arthritis (RA) are at increased risk of low bone density
      and fractures. This study identifies predictors of initiation of dual energy X
      ray absorptiometry (DXA) testing in RA. We identified RA patients from the
      CORRONA registry with >or=1 year follow-up without reported DXA at study entry.
      The primary outcome was report of DXA in the first year of follow-up (DXA
      initiation). Variables associated with DXA initiation were considered for the
      multivariate model. Stepwise logistic regression identified independent
      predictors. Of the 2,717 RA patients without DXA documented at enrollment, 297
      (11%) reported DXA initiation. Independent predictors of DXA initiation included
      age, female sex, history of fracture, steroid use, and physician's assessment of
      RA activity. In conclusion, DXA initiation in RA patients in the CORRONA cohort
      is low despite increased risk of osteoporosis. Predictors of DXA initiation
      include fracture, common risk factors for osteoporosis, and RA-associated
      factors.

PMID- 19104821
TI  - Prospective, intraindividual comparison of MRI versus MDCT for endoleak detection
      after endovascular repair of abdominal aortic aneurysms.
AB  - This study compares MRI and MDCT for endoleak detection after endovascular repair
      of abdominal aortic aneurysms (EVAR). Forty-three patients with previous EVAR
      underwent both MRI (2D T1-FFE unenhanced and contrast-enhanced; 3D triphasic
      contrast-enhanced) and 16-slice MDCT (unenhanced and biphasic contrast-enhanced)
      within 1 week of each other for endoleak detection. MRI was performed by using a
      high-relaxivity contrast medium (gadobenate dimeglumine, MultiHance). Two
      blinded, independent observers evaluated MRI and MDCT separately. Consensus
      reading of MRI and MDCT studies was defined as reference standard. Sensitivity,
      specificity, and accuracy were calculated and Cohen's k statistics were used to
      estimate agreement between readers. Twenty endoleaks were detected in 18 patients
      at consensus reading (12 type II and 8 indeterminate endoleaks). Sensitivity,
      specificity, and accuracy for endoleak detection were 100%, 92%, and 96%,
      respectively, for reader 1 (95%, 81%, 87% for reader 2) for MRI and 55%, 100%,
      and 80% for reader 1 (60%, 100%, 82% for reader 2) for MDCT. Interobserver
      agreement was excellent for MDCT (k = 0.96) and good for MRI (k = 0.81). MRI with
      the use of a high-relaxivity contrast agent is significantly superior in the
      detection of endoleaks after EVAR compared with MDCT. MRI may therefore become
      the preferred technique for patient follow-up after EVAR.

PMID- 19104822
TI  - Evaluation and comparison of cartilage repair tissue of the patella and medial
      femoral condyle by using morphological MRI and biochemical zonal T2 mapping.
AB  - The objective of this study was to use advanced MR techniques to evaluate and
      compare cartilage repair tissue after matrix-associated autologous chondrocyte
      transplantation (MACT) in the patella and medial femoral condyle (MFC). Thirty
      four patients treated with MACT underwent 3-T MRI of the knee. Patients were
      treated on either patella (n = 17) or MFC (n = 17) cartilage and were matched by
      age and postoperative interval. For morphological evaluation, the MR observation
      of cartilage repair tissue (MOCART) score was used, with a 3D-True-FISP sequence.
      For biochemical assessment, T2 mapping was prepared by using a multiecho spin
      echo approach with particular attention to the cartilage zonal structure.
      Statistical evaluation was done by analyses of variance. The MOCART score showed
      no significant differences between the patella and MFC (p > or = 0.05). With
      regard to biochemical T2 relaxation, higher T2 values were found throughout the
      MFC (p < 0.05). The zonal increase in T2 values from deep to superficial was
      significant for control cartilage (p < 0.001) and cartilage repair tissue (p <
      0.05), with an earlier onset in the repair tissue of the patella. The assessment
      of cartilage repair tissue of the patella and MFC afforded comparable
      morphological results, whereas biochemical T2 values showed differences, possibly
      due to dissimilar biomechanical loading conditions.

PMID- 19104823
TI  - CIITA versus IFN-gamma induced MHC class II expression in head and neck cancer
      cells.
AB  - A growing body of evidence suggests that optimal induction of systemic anti-tumor
      immunity requires priming of both the CD4+ and CD8+ T cells that are specific for
      tumor-associated antigens (TAA). Recently, it was shown that MHC class II
      positive tumor cells are able to induce tumor-specific CD4+ T cells, and that
      this event may improve clinical outcome. This has rekindled the interest in
      modulating MHC class II expression in nonprofessional antigen presenting tumor
      cells. The class II transactivator (CIITA) is a major regulator of MHC class I
      and class II expression. We compared, in head and neck cancer cell lines, the
      effect of stable overexpression of CIITA to treatment with IFN-gamma on the cell
      surface expression profile of MHC class I and II molecules. Here, we provide
      evidence that CIITA transfection is more effective than IFN-gamma in inducing MHC
      class II expression. To more thoroughly explore the mechanisms of MHC class II
      induction in this context, we used RT-PCR to measure the mRNA expression pattern
      of HLA-DR, HLA-DM, cathepsin S, and the invariant chain. In contrast to the
      effect of treatment with IFN-gamma, CIITA transfection did not induce cathepsin
      S, an important protease responsible for the degradation of the invariant chain,
      and thus for binding of the peptides to the MHC class II binding groove. These
      findings may have a significant impact on practical and clinical aspects of tumor
      immunotherapeutic strategies.

PMID- 19104824
TI  - Factors associated with bone density in young women with karyotypically normal
      spontaneous premature ovarian failure.
AB  - OBJECTIVE: To evaluate bone density and associated factors in women with
      premature ovarian failure (POF) compared to age-matched women with normal ovarian
      function. METHODS: A cross-sectional study of 50 patients with POF undergoing
      bone mineral densitometry was conducted, compared to 50 women paired by age who
      menstruated regularly. RESULTS: In women with POF, the mean bone mineral density
      measured was 1.22 g/cm(2) at the spine and 0.92 g/cm(2) at the femur, values
      which were significantly lower than in the control group (P < 0.0001). Factors
      directly associated with bone density of the lumbar spine were age and with bone
      density of the femur were BMI and reproductive age. CONCLUSION: Young women with
      POF have a decrease in lumbar spine and femoral bone density. Age, reproductive
      age and BMI were the factors associated with BMD. These women need early
      investigation and treatment to prevent bone loss and minimize fracture risk in
      the future.

PMID- 19104825
TI  - Intraoperative application of "white test" to reduce postoperative bile leak
      after major liver resection: results of a prospective cohort study in 137
      patients.
AB  - PURPOSE: This study aimed to prove the clinical validation of the recently
      developed bile leakage test, "white test" (WT), in major liver resection.
      MATERIALS AND METHODS: From June 2005 to June 2007, the study was carried out in
      a prospective consecutive fashion, including 74 patients without bile leakage
      test as the control group while 63 patients undergoing white test as the study
      group. The incidences of bile leakage within the 30th postoperative day in both
      groups were compared. RESULTS: Postoperative bile leakage was found in 22.9%
      patients in the control group and in 5.3% patients in the WT group, respectively
      (p < 0.01). In univariate analysis, not performing a white test, Klatskin tumor,
      biliary-enteric anastomosis, and longer operation time were associated with an
      increase of bile leakage. The multivariate analysis showed that not performing
      the WT was the only significant factor influencing the occurrence of
      postoperative bile leakage (p = 0.02). CONCLUSIONS: The white test is a feasible
      and sensitive bile leakage test with no obvious disadvantages. It could be a
      possible standardized method to prevent bile leakage in major liver resection.

PMID- 19104826
TI  - Lymph node metastasis in gastrointestinal stromal tumours (GIST) occurs
      preferentially in young patients < or = 40 years: an overview based on our case
      material and the literature.
AB  - PURPOSE: Data on the clinicopathological and biological profiles of
      gastrointestinal stromal tumours (GISTs) at higher risk for nodal metastasis are
      lacking. MATERIALS AND METHODS: We reviewed our own case material and the
      relevant English literature. RESULTS: Regional node metastasis was detected in
      two of 210 GISTs in our case material (1%) corresponding to 6% of 33 patients
      with nodal dissection (mean, 11 nodes) and 25% of those < or = 40 years of age.
      The two patients had a mean age of 32 years, contrasting with a mean age of 65
      years for the whole cohort. One of them had incomplete Carney triad with
      pulmonary chondromas. The literature disclosed a comparable frequency of
      lymphatic spread among paediatric patients and young adults (approximately 20%),
      irrespective of the features of the Carney triad. Although a wider age range was
      reported in isolated reports, a majority (66%) of patients with lymph node
      metastasis were women < or = 40 years with gastric epithelioid/mixed type
      ulcerated endoluminal GIST presenting with GI bleeding. CONCLUSION: Contrasting
      GISTs in elderly patients, lymphatic spread represents a common route of initial
      spread in patients < or = 40 with gastric GISTs, suggesting the need for node
      sampling in this particular subset of GIST patients. The prognostic significance
      of nodal metastasis in GIST patients remains to be further clarified.

PMID- 19104827
TI  - Glass microneedles for force measurements: a finite-element analysis model.
AB  - Changes in developed force (0.1-3.0 microN) observed during contraction of single
      myofibrils in response to rapidly changing calcium concentrations can be measured
      using glass microneedles. These microneedles are calibrated for stiffness and
      deflect on response to developed myofibril force. The precision and accuracy of
      kinetic measurements are highly dependent on the structural and mechanical
      characteristics of the microneedles, which are generally assumed to have a linear
      force-deflection relationship. We present a finite-element analysis (FEA) model
      used to simulate the effects of measurable geometry on stiffness as a function of
      applied force and validate our model with actual measured needle properties. In
      addition, we developed a simple heuristic constitutive equation that best
      describes the stiffness of our range of microneedles used and define limits of
      geometry parameters within which our predictions hold true. Our model also maps a
      relation between the geometry parameters and natural frequencies in air, enabling
      optimum parametric combinations for microneedle fabrication that would reflect
      more reliable force measurement in fluids and physiological environments. We
      propose a use for this model to aid in the design of microneedles to improve
      calibration time, reproducibility, and precision for measuring myofibrillar,
      cellular, and supramolecular kinetic forces.

PMID- 19104828
TI  - In hindsight, life flows from left to right.
AB  - Three experiments investigated the mental representation of meaningful event
      sequences. Experiment 1 used extended (5 min long) naturalistic scenes excerpted
      from commercial movies. Experiments 2 and 3 presented everyday activities by
      means of sequences of six photographs. All experiments found both left-right and
      distance effects in an order decision task, suggesting that when contemplated in
      hindsight, experienced events unfold along a left-to-right analogical mental
      line. Present results are discussed in the context of the mental representation
      of other kinds of ordinal sequences, and other left-right effects reported in non
      ordinal domains.

PMID- 19104829
TI  - Having to identify a target reduces latencies in prosaccades but not in
      antisaccades.
AB  - In a princeps study, Trottier and Pratt (2005) showed that saccadic latencies
      were dramatically reduced when subjects were instructed to not simply look at a
      peripheral target (reflexive saccade) but to identify some of its properties.
      According to the authors, the shortening of saccadic reactions times may arise
      from a top-down disinhibition of the superior colliculus (SC), potentially
      mediated by the direct pathway connecting frontal/prefrontal cortex structures to
      the SC. Using a "cue paradigm" (a cue preceded the appearance of the target), the
      present study tests if the task instruction (Identify vs. Glance) also reduces
      the latencies of antisaccades (AS), which involve prefrontal structures. We show
      that instruction reduces latencies for prosaccade but not for AS. An AS requires
      two processes: the inhibition of a reflexive saccade and the generation of a
      voluntary saccade. To separate these processes and to better understand the task
      effect we also test the effect of the task instruction only on voluntary
      saccades. The effect still exists but it is much weaker than for reflexive
      saccades. The instruction effect closely depends on task demands in executive
      resources.

PMID- 19104832
TI  - Histopathological predictor for regional lymph node metastasis in gastric cancer.
AB  - Regional lymph node metastasis in gastric cancer is a definitive indicator of the
      patient's prognosis. The goal of this study was to identify the predictors for
      lymph node metastasis among all the possible histopathological parameters,
      especially by conducting an objective discrimination of the lymphatic and blood
      vessels. A total of 210 resected primary gastric cancers with or without lymph
      node metastasis were evaluated based on the conventional histopathological
      parameters together with immunohistochemistry using antisera-recognizing
      lymphatic endothelial hyaluronan receptor-1 (LYVE-1), von Willebrand factor, and
      lymphangiogenesis promoter vascular endothelial growth factor-C (VEGF-C)
      antibodies. A multivariate regression analyses of the results indicated that only
      lymphatic invasion was a significant independent predictor of lymph node
      metastasis at any stage of cancer invasion. VEGF-C expression was partially
      related to lymph node metastasis in early gastric cancer. The identification of
      lymphatic invasion by LYVE-1 antibody is therefore useful to predict regional
      lymph node metastasis in gastric cancer.

PMID- 19104833
TI  - The extreme capsule in humans and rethinking of the language circuitry.
AB  - Experimental and imaging studies in monkeys have outlined various long
      association fiber pathways within the fronto-temporo-parietal region. In the
      present study, the trajectory of the extreme capsule (EmC) fibers has been
      delineated in five human subjects using DT-MRI tractography. The EmC seems to be
      a long association fiber pathway, which courses between the inferior frontal
      region and the superior temporal gyrus extending into the inferior parietal
      lobule. Comparison of EmC fibers with the adjacent association fiber pathway, the
      middle longitudinal fascicle (MdLF), in the same subjects reveals that EmC is
      located in a medial and rostral position relative to MdLF flanking in part the
      medial wall of the insula. The EmC can also be differentiated from other
      neighboring fiber pathways such as the external capsule, uncinate fascicle,
      arcuate fascicle, superior longitudinal fascicles II and III, and the inferior
      longitudinal fascicle. Given the location of EmC within the language zone,
      specifically Broca's area in the frontal lobe, and Wernicke's area in the
      temporal lobe and inferior parietal lobule, it is suggested that the extreme
      capsule could have a role in language function.

PMID- 19104835
TI  - Hyperbilirubinemia guideline adherence in Russia illustrates universal
      challenges.
AB  - Guidelines for management of newborn hyperbilirubinemia have existed in Russia
      for many years. We sought to determine the degree to which management of
      hyperbilirubinemia in Russia meets three existing clinical protocols. We
      performed a cross-sectional chart review in a government-run, academic hospital
      in an urban setting in Moscow, Russia. Subjects were admitted to Level II nursery
      at Hospital No.13, were not transferred to a Level III nursery, did not die
      during hospitalization, and had at least one pairing of total serum bilirubin
      (TSB) and clinical evaluation of jaundice. We measured physician adherence to
      three available guidelines based upon TSB levels at which phototherapy and
      exchange transfusions were performed. We identified 594 infants and 1,924
      pairings. Despite availability of TSB to inform decision-making, physicians did
      not follow the protocols. Under Russian and U.S. guidelines, physicians often
      failed to start phototherapy, started phototherapy unnecessarily, and missed
      recommended exchange transfusions. Despite a resource-poor setting, guideline
      adherence in Russia was remarkably similar to that of U.S. physicians. The data
      illustrate the challenge of overcoming physician behavior to standardize
      practice, and raise questions about the presumed higher quality of care in a more
      developed medical system. A new framework for guideline implementation is needed,
      and many of the necessary tools already exist.

PMID- 19104834
TI  - Congenital diaphragmatic hernia: current status and review of the literature.
AB  - Treatment of congenital diaphragmatic hernia (CDH) challenges obstetricians,
      pediatric surgeons, and neonatologists. Persistent pulmonary hypertension (PPHT)
      associated with lung hypoplasia in CDH leads to a high mortality rate at birth.
      PPHT is principally due to an increased muscularization of the arterioles.
      Management of CDH has been greatly improved by the introduction of prenatal
      surgical intervention with tracheal obstruction (TO) and by more appropriate
      postnatal care. TO appears to accelerate fetal lung growth and to increase the
      number of capillary vessels and alveoli. Improvement of postnatal care over the
      last years is mainly due to the avoidance of lung injury by applying low peak
      inflation pressure during ventilation. The benefits of other drugs or technical
      improvements such as the use of inhaled nitric oxide or extracorporeal membrane
      oxygenation (ECMO) are still being debated and no single strategy is accepted
      worldwide. Despite intensive clinical and experimental research, the treatment of
      newborn with CDH remains difficult.

PMID- 19104836
TI  - Inspiratory stridor and dysphagia in two newborn infants caused by ectopic thymus
      tissue.
AB  - We report two cases of ectopic cervical thymus, a solid thymic lesion, and a
      thymus cyst causing inspiratory stridor and mild dysphagia in the neonatal
      period. Because of the rarity of thymic dystopia, the two masses were initially
      misdiagnosed as more common entities, namely, lymph node enlargement and
      lymphangioma, respectively. The correct diagnosis was made only after surgical
      excision and histopathological examination. This case report is completed by a
      short review of embryogenic development, diagnostic procedures with differential
      diagnoses, and therapeutic outcome of ectopic thymus.

PMID- 19104837
TI  - Integrin beta3 down-regulates invasive features of ovarian cancer cells in SKOV3
      cell subclones.
AB  - PURPOSE: To investigate the role of integrin beta3 in invasive features of
      ovarian cancer SKOV3 cells, by comparing different metastatic subclones. METHODS:
      In the present study, two cell subclones, termed as S1 and S21, which possessed
      high and low metastatic potential, respectively, were isolated and established
      from human ovarian cancer parental cell line SKOV3 by the limited dilution
      method. The expressions of integrin alphav, integrin alphavbeta3, integrin beta3,
      E-cadherin, FAK and ILK in the two cell subclones were compared by means of real
      time RT-PCR or flow cytometry. Subsequently, S21 was transfected with siRNA for
      integrin beta3 and the effects of transfection were examined by methyl thiazolyl
      tetrazolium (MTT) assay, colony formation assay, Matrigel invasion assay and cell
      migration assay. RESULTS: The expressions of integrin alphavbeta3, integrin beta3
      and E-cadherin were markedly down-regulated in S1; however, there were no
      significant differences in the expressions of integrin alphav, FAK and ILK beta.
      Of note, more than 70% knockdown of integrin beta3 expression was obtained by
      siRNA technique. The integrin beta3-siRNA-transfected cells showed significant
      increases in cell proliferation, cell migration and invasive activity in contrast
      with the mock-transfected cells. The expressions of integrin alphavbeta3 and E
      cadherin were lower in the integrin beta3-siRNA-transfected cells compared to the
      mock control. CONCLUSION: Integrin beta3, like E-cadherin, may be also a
      suppressor gene down-regulating invasive features of ovarian cancer cells in
      SKOV3 cell subclones.

PMID- 19104839
TI  - Characterization of a deep-coverage carrot (Daucus carota L.) BAC library and
      initial analysis of BAC-end sequences.
AB  - Carrot is the most economically important member of the Apiaceae family and a
      major source of provitamin A carotenoids in the human diet. However, carrot
      molecular resources are relatively underdeveloped, hampering a number of genetic
      studies. Here, we report on the synthesis and characterization of a bacterial
      artificial chromosome (BAC) library of carrot. The library is 17.3-fold redundant
      and consists of 92,160 clones with an average insert size of 121 kb. To provide
      an overview of the composition and organization of the carrot nuclear genome we
      generated and analyzed 2,696 BAC-end sequences (BES) from nearly 2,000 BACs,
      totaling 1.74 Mb of BES. This analysis revealed that 14% of the BES consists of
      known repetitive elements, with transposable elements representing more than 80%
      of this fraction. Eleven novel carrot repetitive elements were identified,
      covering 8.5% of the BES. Analysis of microsatellites showed a comparably low
      frequency for these elements in the carrot BES. Comparisons of the translated BES
      with protein databases indicated that approximately 10% of the carrot genome
      represents coding sequences. Moreover, among eight dicot species used for
      comparison purposes, carrot BES had highest homology to protein-coding sequences
      from tomato. This deep-coverage library will aid carrot breeding and genetics.

PMID- 19104838
TI  - A catalogue of Triticum monococcum genes encoding toxic and immunogenic peptides
      for celiac disease patients.
AB  - The celiac disease (CD) is an inflammatory condition characterized by injury to
      the lining of the small-intestine on exposure to the gluten of wheat, barley and
      rye. The involvement of gluten in the CD syndrome has been studied in detail in
      bread wheat, where a set of "toxic" and "immunogenic" peptides has been defined.
      For wheat diploid species, information on CD epitopes is poor. In the present
      paper, we have adopted a genomic approach in order to understand the potential CD
      danger represented by storage proteins in diploid wheat and sequenced a
      sufficiently large number of cDNA clones related to storage protein genes of
      Triticum monococcum. Four bona fide toxic peptides and 13 immunogenic peptides
      were found. All the classes of storage proteins were shown to contain harmful
      sequences. The major conclusion is that einkorn has the full potential to induce
      the CD syndrome, as already evident for polyploid wheats. In addition, a complete
      overview of the storage protein gene arsenal in T. monococcum is provided,
      including a full-length HMW x-type sequence and two partial HMW y-type sequences.

PMID- 19104840
TI  - Breakpoint mapping and haplotype analysis of three reciprocal translocations
      identify a novel recurrent translocation in two unrelated families:
      t(4;11)(p16.2;p15.4).
AB  - The majority of constitutional reciprocal translocations appear to be unique
      rearrangements arising from independent events. However, a small number of
      translocations are recurrent, most significantly the t(11;22)(q23;q11). Among
      large series of translocations there may be multiple independently ascertained
      cases with the same cytogenetic breakpoints. Some of these could represent
      additional recurrent rearrangements, alternatively they could be identical by
      descent (IBD) or have subtly different breakpoints when examined under higher
      resolution. We have used molecular breakpoint mapping and haplotyping to
      determine the origin of three pairs of reciprocal constitutional translocations,
      each with the same cytogenetic breakpoints. FISH mapping showed one pair to have
      different breakpoints and thus to be distinct rearrangements. Another pair of
      translocations were IBD with identical breakpoint intervals and highly conserved
      haplotypes on the derived chromosomes. The third pair, t(4;11)(p16.2;p15.4), had
      the same breakpoint intervals by aCGH and fosmid mapping but had very different
      haplotypes, therefore they represent a novel recurrent translocation. Unlike the
      t(11;22)(q23;q11), the formation of the t(4;11)(p16.2;p15.4) may have involved
      segmental duplications and sequence homology at the breakpoints. Additional
      examples of recurrent translocations could be identified if the resources were
      available to study more translocations using the approaches described here.
      However, like the t(4;11)(p16.2;p15.4), such translocations are likely to be rare
      with the t(11;22) remaining the only common recurrent constitutional reciprocal
      translocation.

PMID- 19104841
TI  - Alterations of ROBO1/DUTT1 and ROBO2 loci in early dysplastic lesions of head and
      neck: clinical and prognostic implications.
AB  - Deletion of chromosomal 3p12.3 was suggested to be associated with dysplastic
      lesions of head and neck. This region harbors two candidate tumor suppressors
      ROBO1/DUTT1, ROBO2 and two non-coding RNAs (ncRNAs) located at intron 2 of
      ROBO1/DUTT1. Aim of this study is to understand the role of these genes in
      development of head and neck squamous cell carcinoma. A collection of 72
      dysplastic lesions and 116 HNSCC samples and two oral cancer cell lines were
      analyzed for ROBO1/DUTT1 and ROBO2 deletion and promoter methylation.
      ROBO1/DUTT1, ROBO2 and two ncRNAs mRNA expression were analyzed by Q-PCR.
      Immunohistochemical analysis of ROBO1/DUTT1 and ROBO2 was performed. Alterations
      of these genes were correlated with different clinicopathological parameters.
      High frequency of molecular alterations (deletion/methylation) was seen in
      ROBO1/DUTT1 than ROBO2. In mild dysplastic lesions both of these genes showed
      high molecular alterations and remained more or less constant in subsequent
      stages. Q-PCR analysis showed reduced expression of these genes and the two
      ncRNAs. In vitro demethylation experiment by 5-aza-dC showed upregulation of
      ROBO1/DUTT1 and ROBO2 while the expression of the ncRNAs remained unchanged.
      Immunohistochemical analysis of ROBO1/DUTT1 and ROBO2 showed concordance with
      their mRNA expression and molecular alterations. Poor patients' outcome was
      predicted in the cases with alteration of ROBO1/DUTT1 along with tobacco
      addiction and nodal involvement. Our data suggests (a) ROBO1/DUTT1 and the ncRNAs
      are transcribed from different promoters, and (b) inactivation of ROBO1/DUTT1
      could be used as molecular signature for early detection and prognosis of the
      head and neck cancer.

PMID- 19104842
TI  - Diagnostic examination of the child with urolithiasis or nephrocalcinosis.
AB  - Urolithiasis and nephrocalcinosis are more frequent in children then currently
      anticipated, but still remain under- or misdiagnosed in a significant proportion
      of patients, since symptoms and signs may be subtle or misleading. All children
      with colicky abdominal pain or macroscopic hematuria should be examined
      thoroughly for urolithiasis. Also, other, more general, abdominal manifestations
      can be the first symptoms of renal stones. The patients and their family
      histories, as well as physical examination, are important initial steps for
      diagnostic evaluation. Thereafter, diagnostic imaging should be aimed at the
      location of calculi but also at identification of urinary tract anomalies or
      acute obstruction due to stone disease. This can often be accomplished by
      ultrasound examination alone, but sometimes radiological methods such as plain
      abdominal films or more sensitive non-enhanced computed tomography are necessary.
      Since metabolic causes are frequent in children, diagnostic evaluation should be
      meticulous so that metabolic disorders that cause recurrent urolithiasis or even
      renal failure, such as the primary hyperoxalurias and others, can be ruled out.
      The stone is not the disease itself; it is only one serious sign! Therefore,
      thorough and early diagnostic examination is mandatory for every infant and child
      with the first stone event, or with nephrocalcinosis.

PMID- 19104843
TI  - Randomized clinical trial of an intensive nursing-based pain education program
      for cancer outpatients suffering from pain.
AB  - INTRODUCTION: The prevalence of pain in patients with cancer is still too high.
      Factors relating to ineffective pain treatment fall into three categories: the
      health care system, professional care providers, and patients. In patients,
      various barriers lead to noncompliance. Previous educational interventions have
      increased their knowledge of pain and decreased short-term pain levels. In this
      randomized controlled trial, the authors investigated how an intensive home-based
      education program given by nurses affected short-term and long-term pain levels.
      MATERIALS AND METHODS: One hundred and twenty cancer patients were randomized to
      receive either the pain education program (PEP) or usual care. Pain, knowledge,
      quality of life, anxiety, and depression were measured at baseline and after 4
      and 8 weeks. In the intervention group, effects on symptom levels were
      communicated to the treating physician. RESULTS: The level of pain had decreased
      at 4 weeks, but not at 8 weeks. Significant decreases in pain only persisted in
      those patients with a high pain score at baseline. Knowledge of pain
      significantly increased in the intervention group. No correlation was found
      between increased pain knowledge and decreased pain levels. CONCLUSIONS: The PEP
      given by nurses lowered pain intensity levels in cancer patients and increased
      their knowledge of pain. More attention should be paid to patient education and
      to communication between patients and health professionals regarding pain and
      pain management.

PMID- 19104844
TI  - Symptom-monitoring behaviors of rural cancer patients and survivors.
AB  - GOALS OF WORK: Symptom monitoring is described among rural cancer patients and
      survivors with comparison across study variables. MATERIALS AND METHODS: An
      anonymous survey was mailed to adult cancer patients and survivors. Sampling was
      via a cancer center serving a region of a US rural-frontier state. Symptom
      monitoring was measured as keeping written track of symptoms, side effects,
      trends in how one is feeling, and/or limits to what one can do. MAIN RESULTS:
      Useable response rate was 60.4% (134/222). Respondents were on average 62.3 years
      old, 53.0% were female, and 52.3% had earned less than a college degree. Breast
      (30.6%) and prostate (28.4%) cancers were most common. Symptom monitoring was
      reported and confirmed via tracking means, by 32.1% of respondents. Symptom
      monitoring was associated with "shared" or "passive" symptom management
      decisions, keeping written track of questions to ask providers and answers
      received, report of fatigue, and having received the suggestion or advice on how
      to monitor. Symptom monitoring was not associated with age, education, sex,
      number of symptoms, or being given something with which to monitor. CONCLUSIONS:
      Symptom monitoring apart from intervention appears common among rural cancer
      patients and survivors. Findings support using multi-dimensional ways to inquire
      of, and refer to, such behavior. Data show symptom monitoring is more common
      among those suffering cancer-related fatigue, indicating opportunities for
      intervention to optimize monitoring for improved outcomes. Findings also suggest
      symptom-monitoring patients may rely on, or interact more with, providers
      regarding symptom management.

PMID- 19104845
TI  - Equipotent doses to switch from high doses of opioids to transdermal
      buprenorphine.
AB  - INTRODUCTION: The aim of this study was to evaluate the equianalgesic ratio of
      transdermal buprenorphine (TD BUP) with oral morphine and TD fentanyl in a sample
      of consecutive cancer patients receiving stable doses of 120-240 mg of oral
      morphine or 50-100 microg of TD fentanyl, reporting adequate pain and symptom
      control. MATERIALS, METHODS, AND RESULTS: Patients receiving daily stable doses
      of opioids for more than 6 days, with no more than two doses of oral morphine (20
      and 40 mg, respectively) as needed, were switched to TD BUP using a fentanyl-BUP
      ratio of 0.6:0.8 and an oral morphine-BUP ratio of 70:1. Opioid doses, pain and
      symptom intensity, global satisfaction, and number of breakthrough medication
      were recorded before switching (T0), 3 days after (T3), and 6 days after (T6).
      Eleven patients were recruited in a period of 1 year, and data were complete for
      ten patients. The mean age was 61.6 (SD 9.5), and five patients were males. No
      significant changes in pain and symptom intensity were found, except improvement
      in reported constipation (p = 0.014), as well as in global satisfaction with the
      analgesic treatment. No significant changes in breakthrough pain medication were
      observed. CONCLUSION: The results of this study suggest that stable patients
      receiving relatively high doses of oral morphine or TD fentanyl could be safely
      switched to TD BUP, by using a ratio of 70:1 and 0.6:0.8, respectively,
      maintaining the same level of analgesia.

PMID- 19104846
TI  - Ectomycorrhizal fungal community in alkaline-saline soil in northeastern China.
AB  - Alkaline-saline soil is widespread in arid and semiarid regions of the world and
      causes severe environmental and agricultural problems. To advance our
      understanding of the adaptation of ectomycorrhizal fungi (EMF) to alkaline-saline
      soil, we investigated EMF communities on Mongolian willow (Salix
      linearistipularis) growing in alkaline-saline soil (up to pH 9.2) in northeastern
      China. In total, 75 root samples were collected from 25 willow individuals over
      4.7 ha. To identify fungal species in ectomycorrhizal root tips, we used terminal
      restriction fragment length polymorphism and sequencing analyses of the internal
      transcribed spacer region of ribosomal DNA. We detected 11 EMF species, including
      species of Inocybe, Hebeloma, and Tomentella of the Basidiomycota and three
      Ascomycota species. The EMF richness of the study site was estimated to be 15-17
      using major estimators. The most abundant species was Geopora sp. 1, while no
      Geopora-dominated EMF communities have been reported so far. Phylogenetic
      analysis showed that the phylogroup including Geopora sp. 1 has been found mostly
      in alkaline soil habitats, indicating its adaptation to high soil pH. Because EMF
      are indispensable for host plant growth, the EMF species detected in this study
      may be useful for restoration of alkaline-saline areas.

PMID- 19104847
TI  - Influence of soil organic matter decomposition on arbuscular mycorrhizal fungi in
      terms of asymbiotic hyphal growth and root colonization.
AB  - Soil organic matter is known to influence arbuscular mycorrhizal (AM) fungi, but
      limited information is available on the chemical components in the organic matter
      causing these effects. We studied the influence of decomposing organic matter
      (pure cellulose and alfalfa shoot and root material) on AM fungi after 30, 100,
      and 300 days of decomposition in nonsterile soil with and without addition of
      mineral N and P. Decomposing organic matter affected maize root length colonized
      by the AM fungus Glomus claroideum in a similar manner as other plant growth
      parameters. Colonized root length was slightly increased by both nitrogen and
      phosphorus application and plant materials, but not by application of cellulose.
      In vitro hyphal growth of Glomus intraradices was increased by soil extracts from
      the treatments with all types of organic materials independently of mineral N and
      P application. Pyrolysis of soil samples from the different decomposition
      treatments revealed in total 266 recognizable organic compounds and in vitro
      hyphal growth of G. intraradices in soil extract positively correlated with 33 of
      these compounds. The strongest correlation was found with 3,4,5-trimethoxybenzoic
      acid methyl ester. This compound is a typical product of pyrolysis of phenolic
      compounds produced by angiosperm woody plants, but in our experiment, it was
      produced mainly from cellulose by some components of the soil microflora. In
      conclusion, our results indicate that mycelia of AM fungi are influenced by
      organic matter decomposition both via compounds released during the decomposition
      process and also by secondary metabolites produced by microorganisms involved in
      organic matter decomposition.

PMID- 19104848
TI  - Phylogenetic analysis of the Glomeromycota by partial beta-tubulin gene
      sequences.
AB  - The 3' end of the beta-tubulin gene was amplified from 50 isolates of 45 species
      in Glomeromycota. The analyses included a representative selection of all
      families except Pacisporaceae and Geosiphonaceae. Phylogenetic analyses excluded
      three intron regions at the same relative positions in all species due to
      sequence and length polymorphisms. The beta-tubulin gene phylogeny was similar to
      the 18S rRNA gene phylogeny at the family and species level, but it was not
      concordant at the order level. Species in Gigasporaceae and Glomeraceae grouped
      together but without statistical support. Paralogous sequences in Glomus species
      likely contributed to phylogenetic ambiguity. Trees generated using different
      fungal phyla as out-groups yielded a concordant topology. Family relationships
      within the Glomeromycota did not change regardless if the third codon position
      was included or excluded from the analysis. Multiple clones from three isolates
      of Scutellospora heterogama yielded divergent sequences. However, phylogenetic
      patterns suggested that only a single copy of the beta-tubulin gene was present,
      with variation attributed to intraspecific sequence divergence.

PMID- 19104852
TI  - Identification of fungal species by fragment length analysis of the internally
      transcribed spacer 2 region.
AB  - The rapid identification of fungal pathogens in clinical specimens is a
      prerequisite for timely onset of the most appropriate treatment. The aim of the
      present study was to develop a sensitive and rapid method for the species
      specific identification of clinically relevant fungi. We employed fluorescent
      polymerase chain reaction (PCR)-fragment length analysis of the highly variable
      internally transcribed spacer 2 (ITS2) region to identify individual fungal
      species by their specific amplicon sizes. The specificity of the technique was
      ascertained by the detailed analysis of 96 strains derived from 60 different
      human-pathogenic fungal species. To achieve adequate sensitivity for species
      identification in patients with invasive fungal infection, who often display very
      low pathogen loads in peripheral blood, the ITS2 region was amplified by semi
      nested PCR prior to amplicon-length analysis. Serial specimens from 26 patients
      with documented fungal infections were investigated. The fungal pathogens
      identified included different Aspergillus and Candida species, Rhizopus oryzae
      and Fusarium oxysporum. Fragment length analysis of the ITS2 region upon
      amplification by semi-nested PCR permits the sensitive identification of fungal
      species. The technique can be readily implemented in routine diagnostics.

PMID- 19104850
TI  - Repair, regenerative and supportive therapies of the annulus fibrosus:
      achievements and challenges.
AB  - Lumbar discectomy is a very effective therapy for neurological decompression in
      patients suffering from sciatica due to hernia nuclei pulposus. However, high
      recurrence rates and persisting post-operative low back pain in these patients
      require serious attention. In the past decade, tissue engineering strategies have
      been developed mainly targeted to the regeneration of the nucleus pulposus (NP)
      of the intervertebral disc. Accompanying techniques that deal with the damaged
      annulus fibrous are now increasingly recognised as mandatory in order to prevent
      re-herniation to increase the potential of NP repair and to confine NP
      replacement therapies. In the current review, the requirements, achievements and
      challenges in this quickly emerging field of research are discussed.

PMID- 19104851
TI  - Methicillin-resistant Staphylococcus aureus (MRSA) among dental patients: a
      problem for infection control in dentistry?
AB  - We assessed the frequency of carriers of methicillin-resistant Staphylococcus
      aureus (MRSA) among 500 dental patients of a university clinic. From each
      participant, two specimens were taken from the anterior nares and the pharynx and
      analysed by culture. The participants completed a questionnaire on possible risk
      factors of MRSA infection. Two hundred ten individuals carried S. aureus, 90 in
      the nares only, 51 in the throat only and 69 in nares and throat. Isolates of 208
      patients were methicillin-sensitive; two isolates were methicillin-resistant,
      both carried in the throat exclusively. In conclusion, the frequency of nasal
      and/or throat carriers of MRSA among dental patients was low and suggests few
      opportunities of exposure in the dental clinic assessed.

PMID- 19104854
TI  - Effect of meteorological variables on the incidence of lower urinary tract
      infections.
AB  - Several types of infections involving the respiratory tract have a seasonal
      variation. We further examined whether lower urinary tract infections (UTIs) are
      associated with meteorological parameters. We retrospectively evaluated the
      correlation of the weekly percentage of house call visits for lower UTIs
      (relatively to all house call visits, excluding those for respiratory tract
      infections), performed by "SOS Doctors" specialized physicians in Attica, Greece
      (1/11/2000-18/1/2005), with the average weekly temperature and humidity, recorded
      at the same area, 3 days earlier. Three thousand two hundred and twenty-one
      visits for lower UTIs were recorded in patients of 62.9 +/- 21.0 years of age.
      House call visits for lower UTIs, as defined above, correlated with the average
      weekly temperature (Spearman's rho+0.468) and humidity (Spearman's rho -0.394);
      similarly, if respiratory tract infections were not excluded from the
      calculations (Spearman's rho +0.491 and -0.406, respectively); or if a 2-day lag
      between measurements was used (Spearman's rho +0.468 and -0.386, respectively).
      All the above findings were significant (p<0.001). In conclusion, in a population
      that consisted mainly of patients of advanced age, higher temperature and
      decreased humidity are associated with an increase in house call visits for lower
      UTIs. The awareness of this association may facilitate preventive public health
      strategies. [corrected]

PMID- 19104853
TI  - Detection of Toxoplasma gondii oocysts in environmental soil samples using
      molecular methods.
AB  - Infections caused by Toxoplasma gondii are prevalent in humans and animals
      throughout the world. So far, there is no sufficient information concerning T.
      gondii oocysts prevalence in the environment, especially in soil. Therefore, the
      aim of this study was to estimate occurrence of T. gondii oocysts in soil and
      determine the genotype of detected parasites. A total of 101 soil samples were
      taken from different sites (sand-pits, "farming ground", areas around rubbish
      dumps) located in the Tri-City (Poland). Oocysts were recovered using the
      flotation method. Then, PCR reactions targeting the B1 gene were performed for
      specific T. gondii detection. The positive samples were further confirmed by PCR
      amplification of a repetitive element (REP) sequence [GenBank accession number
      AF146527]. Toxoplasma DNA was found in 18 samples. Among them, seven samples were
      successfully genotyped at the SAG2 locus. They were classified as SAG2 type I (5
      samples) and SAG2 type II (2 samples). This is one of the first investigations
      describing T. gondii oocyst detection in environmental soil samples with rapid
      molecular detection methods and genotyping. The results of our findings showed
      that soil contaminated with T. gondii oocysts may play a role in the epidemiology
      of human toxoplasmosis in Poland.

PMID- 19104855
TI  - Experimental study of de Vries properties in antiferroelectric smectic liquid
      crystals.
AB  - Results of the experimental study on different antiferroelectric liquid crystal
      (AFLC) materials are presented using a number of techniques such as the optical
      birefringence, electro-optics and the measurements of optical thickness of free
      standing films. Despite differences in the molecular structures of the various
      AFLC materials studied, these are found to exhibit a de Vries type of smecticA
      (SmA) properties in a temperature range higher than SmC. This correlation leads
      to the conclusion that these two classes of liquid crystals are related to each
      other. Furthermore, we suggest that these arise from the same physical mechanism,
      namely the existence of the weak synclinic (or reduced anticlinic) correlations
      between the neighbouring molecular tilt directions.

PMID- 19104856
TI  - The ideal polymer chain near planar hard wall beyond the Dirichlet boundary
      conditions.
AB  - We present a new ab initio approach to describe the statistical behavior of long
      ideal polymer chains near a plane hard wall. Forbidding the solid half-space to
      the polymer explicitly (by the use of Mayer functions) without any other
      requirement, we derive and solve an exact integral equation for the partition
      function G (D)(r,r', N) of the ideal chain consisting of N bonds with the ends
      fixed at the points r and r'. The expression for G(r,r', s) is found to be the
      sum of the commonly accepted Dirichlet result G (D)(r,r', N) = G (0)(r,r', N) - G
      (0)(r,r'', N) , where r'' is the mirror image of r', and a correction. Even
      though the correction is small for long chains, it provides a non-zero value of
      the monomer density at the very wall for finite chains, which is consistent with
      the pressure balance through the depletion layer (so-called wall or contact
      theorem). A significant correction to the density profile (of magnitude
      1/[Formula: see text]is obtained away from the wall within one coil radius.
      Implications of the presented approach for other polymer-colloid problems are
      discussed.

PMID- 19104857
TI  - Detection of the tagged or untagged photons in acousto-optic imaging of thick
      highly scattering media by photorefractive adaptive holography.
AB  - We propose an original adaptive wavefront holographic setup based on the
      photorefractive effect (PR), to make real-time measurements of acousto-optic
      signals in thick scattering media, with a high flux collection at high rates for
      breast tumor detection. We describe here our present state of the art and
      understanding on the problem of breast imaging with PR detection of the acousto
      optic signal.

PMID- 19104858
TI  - Tetracene film morphology: comparative atomic force microscopy, X-ray diffraction
      and ellipsometry investigations.
AB  - X-ray diffraction, atomic force microscopy and spectroscopic ellipsometry were
      used to study tetracene thin films as a function of deposition rate. A
      comparative analysis of the thickness and roughness values allows for detailed
      modelling of the film morphology. An interdigitated growth mode is established
      for the coexisting thin film and bulk phases. By comparison with the respective
      quinone-derivative of tetracene, we were additionally able to identify reaction
      products by their optical response.

PMID- 19104859
TI  - Purification and characterization of a novel thermoacid-stable fibrinolytic
      enzyme from Staphylococcus sp. strain AJ isolated from Korean salt-fermented
      Anchovy-joet.
AB  - A novel fibrinolytic enzyme (AJ) was purified from Staphylococcus sp. strain AJ
      screened from Korean salt-fermented Anchovy-jeot. Relative molecular weight of AJ
      was determined as 26 kDa by using SDS-PAGE and fibrin zymography. Based on a 2D
      gel, AJ was found to consist of three active isoforms (pI 5.5-6.0) with the same
      N-terminal amino acid sequence. AJ exhibited optimum pH and temperature at 2.5
      3.0 and 85 degrees C, respectively. AJ kept 85% of the initial activity after
      heating at 100 degrees C for 20 min on the zymogram gel. The Michaelis constant
      (K (m)) and K (cat) values of AJ towards alpha-casein were 0.38 mM and 19.73 s(
      1), respectively. AJ cleaved the A alpha-chain of fibrinogen but did not affect
      the B beta- and gamma-chains, indicating that it is an alpha-fibrinogenase. The
      fibrinolytic activity was inhibited by diisopropyl fluorophosphate, indicating AJ
      is a serine protease. Interestingly, AJ was very stable at acidic condition, SDS,
      and heat (100 degrees C), whereas it was easily degraded at neutral and alkaline
      conditions. In particular, AJ formed an active homo-dimer in the pH range from
      7.0 to 8.0. To our knowledge, a similar combination of acid and heat stability
      has not yet been reported for other fibrinolytic enzymes.

PMID- 19104860
TI  - Synthesis of 4-nitrophenyl acetate using molecular sieve-immobilized lipase from
      Bacillus coagulans.
AB  - Extracellular lipase from Bacillus coagulans BTS-3 was immobilized on (3 A x 1.5
      mm) molecular sieve. The molecular sieve showed approximately 68.48% binding
      efficiency for lipase (specific activity 55 IU mg(-1)). The immobilized enzyme
      achieved approx 90% conversion of acetic acid and 4-nitrophenol (100 mM each)
      into 4-nitrophenyl acetate in n-heptane at 65 degrees C in 3 h. When alkane of C
      chain length other than n-heptane was used as the organic solvent, the conversion
      of 4-nitrophenol and acetic acid was found to decrease. About 88.6% conversion of
      the reactants into ester was achieved when reactants were used at molar ratio of
      1:1. The immobilized lipase brought about conversion of approximately 58% for
      esterification of 4-nitrophenol and acetic acid into 4-nitrophenyl acetate at a
      temperature of 65 degrees C after reuse for 5 cycles.

PMID- 19104861
TI  - Metals tolerance in moderately thermophilic isolates from a spent copper sulfide
      heap, closely related to Acidithiobacillus caldus, Acidimicrobium ferrooxidans
      and Sulfobacillus thermosulfidooxidans.
AB  - Selective enrichments enabled the recovery of moderately thermophilic isolates
      with copper bioleaching ability from a spent copper sulfide heap. Phylogenetic
      and physiological characterization revealed that the isolates were closely
      related to Sulfobacillus thermosulfidooxidans, Acidithiobacillus caldus and
      Acidimicrobium ferrooxidans. While isolates exhibited similar physiological
      characteristics to their corresponding type strains, in general they displayed
      similar or greater tolerance of high copper, zinc, nickel and cobalt
      concentrations. Considerable variation was found between species and between
      several strains related to S. thermosulfidooxidans. It is concluded that
      adaptation to metals present in the bioleaching heap from which they were
      isolated contributed to but did not entirely explain high metals tolerances.
      Higher metals tolerance did not confer stronger bioleaching performance,
      suggesting that a physical, mineralogical or chemical process is rate limiting
      for a specific ore or concentrate.

PMID- 19104862
TI  - Statistical optimization of medium composition for aspergiolide A production by
      marine-derived fungus Aspergillus glaucus.
AB  - Statistical methodologies were employed to optimize submerged culture medium for
      the production of a novel antineoplastic compound aspergiolide A by a marine
      derived fungus Aspergillus glaucus HB1-19 for the first time. Orthogonal design
      was preformed to determine the initial composition. Then Plackett-Burman design
      was applied to evaluate the influence of related nutrients, and yeast extract
      paste, soybean powder and sodium glutamate were confirmed as critical factors in
      the medium. Response surface methodology (RSM) was finally taken as an effective
      approach to optimize the combination of the obtained three significant factors.
      The predicted maximal aspergiolide A production of 62.4 mg/L appeared at the
      region where the concentrations of sodium glutamate, soybean powder, and yeast
      extract paste were 2, 1, and 1.07 g/L, respectively. Under the proposed optimized
      conditions, the experimental aspergiolide A production reached 71.2 mg/L. The
      correlation between predicted value and measured value of these experiments
      proved the validity of the response model. After optimization, aspergiolide A
      production increased 4.22 times compared to that of the original medium.
      Elemental analysis was finally taken into consideration, and carbon-nitrogen
      ratio in the medium increased from 20.1:1 to 86.6:1. This great difference was
      inferred as the most important reason for production enhancement by metabolic
      pathway analysis.

PMID- 19104863
TI  - Phytoremediation to remove nutrients and improve eutrophic stormwaters using
      water lettuce (Pistia stratiotes L.).
AB  - BACKGROUND, AIM, AND SCOPE: Water quality impairment by nutrient enrichment from
      agricultural activities has been a concern worldwide. Phytoremediation technology
      using aquatic plants in constructed wetlands and stormwater detention ponds is
      increasingly applied to remediate eutrophic waters. The objectives of this study
      were to evaluate the effectiveness and potential of water lettuce (Pistia
      stratiotes L.) in removing nutrients including nitrogen (N) and phosphorus (P)
      from stormwater in the constructed water detention systems before it is
      discharged into the St. Lucie Estuary, an important surface water system in
      Florida, using phytoremediation technologies. MATERIALS AND METHODS: In this
      study, water lettuce (P. stratiotes) was planted in the treatment plots of two
      stormwater detention ponds (East and West Ponds) in 2005-2007 and water samples
      from both treatment and control plots were weekly collected and analyzed for
      water quality properties including pH, electrical conductivity, turbidity,
      suspended solids, and nutrients (N and P). Optimum plant density was maintained
      and plant samples were collected monthly and analyzed for nutrient contents.
      RESULTS: Water quality in both ponds was improved, as evidenced by decreases in
      water turbidity, suspended solids, and nutrient concentrations. Water turbidity
      was decreased by more than 60%. Inorganic N (NH(4) (+) and NO(3) (-))
      concentrations in treatment plots were more than 50% lower than those in control
      plots (without plant). Reductions in both PO(4) (3-) and total P were
      approximately 14-31%, as compared to the control plots. Water lettuce contained
      average N and P concentrations of 17 and 3.0 g kg(-1), respectively, and removed
      190-329 kg N ha(-1) and 25-34 kg P ha(-1) annually. DISCUSSION: Many aquatic
      plants have been used to remove nutrients from eutrophic waters but water lettuce
      proved superior to most other plants in nutrient removal efficiency, owing to its
      rapid growth and high biomass yield potential. However, the growth and nutrient
      removal potential are affected by many factors such as temperature, water
      salinity, and physiological limitations of the plant. Low temperature, high
      concentration of salts, and low concentration of nutrients may reduce the
      performance of this plant in removing nutrients. CONCLUSIONS: The results from
      this study indicate that water lettuce has a great potential in removing N and P
      from eutrophic stormwaters and improving other water quality properties.

PMID- 19104864
TI  - Effects of public health interventions on industrial emissions and ambient air in
      Cartagena, Spain.
AB  - BACKGROUND, AIM, AND SCOPE: Ten years of public health interventions on
      industrial emissions to clean air were monitored for the Mediterranean city of
      Cartagena. During the 1960s, a number of large chemical and non-ferrous
      metallurgical factories were established that significantly deteriorated the
      city's air quality. By the 1970s, the average annual air concentration of sulfur
      dioxide (SO2) ranged from 200 to 300 microg/m3 (standard conditions units). In
      1979, the Spanish government implemented an industrial intervention plan to
      improve the performance of factories and industrial air pollution surveillance.
      Unplanned urban development led to residential housing being located adjacent to
      three major factories. Factory A produced lead, factory B processed zinc from ore
      concentrates, and factory C produced sulfuric acid and phosphates. This, in
      combination with the particular abrupt topography and frequent atmospheric
      thermal inversions, resulted in the worsening of air quality and heightening
      concern for public health. In 1990, the City Council authorized the immediate
      intervention at these factories to reduce or shut down production if ambient
      levels of SO2 or total suspended particles (TSP) exceeded a time-emission
      threshold in pre-established meteorological contexts. The aim of this research
      was to assess the appropriateness and effectiveness of the intervention plan
      implemented from 1992 to 2001 to abate industrial air pollution. MATERIALS AND
      METHODS: The maximum daily 1-h ambient air level of SO2, NO2, and TSP pollutants
      was selected from one of the three urban automatic stations, designed to monitor
      ambient air quality around industrial emissions sources. The day on which an
      intervention took place to reduce and/or interrupt industrial production by
      factory and pollutant was defined as a control day, and the day after an
      intervention as a post-control day. To assess the short-term intervention effect
      on air quality, an ecological time series design was applied, using regression
      analysis in generalized additive models, focusing on day-to-day variations of
      ambient air pollutants levels. Two indicators were estimated: (a)
      appropriateness, the ratio between mean levels of the pollutant for control days
      versus the other days, and (b) effectiveness, the ratio between mean levels of
      the pollutant for post-control days versus the other days. Ratios in regression
      analyses were adjusted for trend, seasonality, temperature, humidity and
      atmospheric pressure, calendar day, and special events as well as the other
      pollutants. RESULTS: A total of 702 control days were made on the factories'
      industrial production during the 10-year period. Fifteen reductions and five
      shutdown control days took place at factory A for ambient air SO2. At factory B,
      more controls were carried out for the SO2 pollutant in the years 1992-1993 and
      1997. At factory C, the control days for SO2 decreased from 59 reductions and 14
      shutdowns to a minimum from 1995 onwards, whereas the controls on TSP were more
      frequent, reaching a maximum of 99 reductions and 47 shutdowns in the last year.
      SO2 ambient air mean levels ranged from 456 to 699 microg/m(3) among factories on
      reduction control days and between 624 and 1,010 microg/m(3) on shutdown days.
      The TSP ambient air mean levels were 428 and 506 microg/m(3) on reduction and
      shutdown days, respectively. For all types of control days and factories, a mean
      ratio of 104% (95% confidence interval [CI] 88 to 121) in SO(2) levels was
      obtained and a mean ratio of 67% (95% CI 59 to 75) in TSP levels. Post-control
      days at all factories showed a mean ratio of -16% (95% CI -7 to -24) in SO(2)
      levels and a mean ratio of -13% (95% CI -7 to -19) in TSP levels. DISCUSSION:
      Interventions on industrial production based on the urban SO(2) and TSP ambient
      air levels were justified by the high concentrations detected. The best
      assessment of the interventions' effectiveness would have been to utilize the
      ambient air pollutant concentration readings from the entire time of the
      production shutdowns or reductions; however, the daily hourly maximum turned out
      to be a useful indicator because of meteorological factors influencing the
      diurnal concentration profile. A substantial number of interventions were carried
      out from 1 to 3 AM: , when vehicular traffic was minimum. On the other hand,
      atmospheric stability undergoes diurnal cycling in the autumn-winter period due
      to thermal inversion, which reaches maximum levels around daybreak. Therefore,
      this increases the ambient air levels and justified the interventions carried out
      at daybreak in spite of the traffic influence. CONCLUSIONS: All the interventions
      for SO(2) and TSP were carried out when the measured ambient air levels of
      pollutants were exceeded, which shows the appropriateness of the intervention
      program. This excess was greater when intervening on SO(2) than on the TSP
      levels. For both ambient air levels of SO(2) and TSP, significant drops in air
      pollution were achieved from all three factories following activity reductions.
      The production shutdown controls were very effective, because they returned
      excess levels, higher than in the reduction controls, to everyday mean values.
      RECOMMENDATIONS AND PERSPECTIVES: The Cartagena City observational system of
      intermittent control has proven to effectively reduce industrial emissions'
      impact on ambient air quality. This experienced model approach could serve well
      in highly polluted industrial settings. From a public health perspective, studies
      are needed to assess that the industrial interventions to control air pollution
      were related to healthier human populations. Legislation was needed to allow the
      public administration to take direct actions upon the polluting industries.

PMID- 19104866
TI  - Contaminants and nutrients : availability, accumulation/exclusion and plant
      microbia-soil interactions. EU COST 859 Meeting at Smolenice, Slovakia, 22-24 May
      2008.

PMID- 19104865
TI  - The formation and fate of chlorinated organic substances in temperate and boreal
      forest soils.
AB  - BACKGROUND, AIM AND SCOPE: Chlorine is an abundant element, commonly occurring in
      nature either as chloride ions or as chlorinated organic compounds (OCls).
      Chlorinated organic substances were long considered purely anthropogenic
      products; however, they are, in addition, a commonly occurring and important part
      of natural ecosystems. Formation of OCls may affect the degradation of soil
      organic matter (SOM) and thus the carbon cycle with implications for the ability
      of forest soils to sequester carbon, whilst the occurrence of potentially toxic
      OCls in groundwater aquifers is of concern with regard to water quality. It is
      thus important to understand the biogeochemical cycle of chlorine, both inorganic
      and organic, to get information about the relevant processes in the forest
      ecosystem and the effects on these from human activities, including forestry
      practices. A survey is given of processes in the soil of temperate and boreal
      forests, predominantly in Europe, including the participation of chlorine, and
      gaps in knowledge and the need for further work are discussed. RESULTS: Chlorine
      is present as chloride ion and/or OCls in all compartments of temperate and
      boreal forest ecosystems. It contributes to the degradation of SOM, thus also
      affecting carbon sequestration in the forest soil. The most important source of
      chloride to coastal forest ecosystems is sea salt deposition, and volcanoes and
      coal burning can also be important sources. Locally, de-icing salt can be an
      important chloride input near major roads. In addition, anthropogenic sources of
      OCls are manifold. However, results also indicate the formation of chlorinated
      organics by microorganisms as an important source, together with natural abiotic
      formation. In fact, the soil pool of OCls seems to be a result of the balance
      between chlorination and degradation processes. Ecologically, organochlorines may
      function as antibiotics, signal substances and energy equivalents, in descending
      order of significance. Forest management practices can affect the chlorine cycle,
      although little is at present known about how. DISCUSSION: The present data on
      the apparently considerable size of the pool of OCls indicate its importance for
      the functioning of the forest soil system and its stability, but factors
      controlling their formation, degradation and transport are not clearly
      understood. It would be useful to estimate the significance and rates of key
      processes to be able to judge the importance of OCls in SOM and litter
      degradation. Effects of forest management processes affecting SOM and chloride
      deposition are likely to affect OCls as well. Further standardisation and
      harmonisation of sampling and analytical procedures is necessary. CONCLUSIONS AND
      PERSPECTIVES: More work is necessary in order to understand and, if necessary,
      develop strategies for mitigating the environmental impact of OCls in temperate
      and boreal forest soils. This includes both intensified research, especially to
      understand the key processes of formation and degradation of chlorinated
      compounds, and monitoring of the substances in question in forest ecosystems. It
      is also important to understand the effect of various forest management
      techniques on OCls, as management can be used to produce desired effects.

PMID- 19104867
TI  - Selenite resistant rhizobacteria stimulate SeO(3) (2-) phytoextraction by
      Brassica juncea in bioaugmented water-filtering artificial beds.
AB  - BACKGROUND, AIM, AND SCOPE: Selenium is a trace metalloid of global environmental
      concern. The boundary among its essentiality, deficiency, and toxicity is narrow
      and mainly depends on the chemical forms and concentrations in which this element
      occurs. Different plant species-including Brassica juncea-have been shown to play
      a significant role in Se removal from soil as well as water bodies. Furthermore,
      the interactions between such plants, showing natural capabilities of metal
      uptake and their rhizospheric microbial communities, might be exploited to
      increase both Se scavenging and vegetable biomass production in order to improve
      the whole phytoextraction efficiency. The aim of the present study was to
      evaluate the capability of selenite removal of B. juncea grown in hydroponic
      conditions on artificially spiked effluents. To optimize phytoextraction
      efficiency, interactions between B. juncea and rhizobacteria were designedly
      elicited. MATERIALS AND METHODS: Firstly, B. juncea was grown on water-filtering
      agriperlite beds in the presence of three different selenite concentrations,
      namely, 0.2, 1.0, and 2.0 mM. Plant growth was measured after 3 and 6 weeks of
      incubation in order to establish the selenite concentration at which the best
      plant biomass production could be obtained. Afterwards, water-filtering
      agriperlite beds were inoculated either with a selenium-acclimated microbial
      community deriving from the rhizosphere of B. juncea grown, erstwhile, in a
      selenite-amended soil or with axenic cultures of two bacterial strains, vicelike
      Bacillus mycoides SeITE01 and Stenotrophomonas maltophilia SeITE02, previously
      isolated and described for their high resistance to selenite. These latter were
      seeded separately or as a dual consortium. Selenite was amended at a final
      concentration of 1.0 mM. Total Se content in plant tissues (both shoots and
      roots), plant biomass production, and persistence of bioaugmented microbial
      inocula during the experimental time were monitored. Moreover, parameters such as
      bioconcentration factor (BF) and phytoextraction efficiency (PE) were determined
      at the end of the testing run to evaluate the effects of the different
      bioaugmentation strategies adopted on selenite phytoextraction efficiency of B.
      juncea. RESULTS: A general but significant increase in capacity to extract and
      transport selenium to the epigeous plant compartments was recorded in B. juncea
      grown in beds augmented with microbial inocula, except for the treatment with B.
      mycoides SeITE01 alone. Nevertheless, a severe decrease in vegetable biomass
      production was observed after all microbial treatments with the exception of the
      plants that had received only S. maltophilia SeITE02. Actually, an increase in
      selenium phytoextraction efficiency up to 65% was observed in B. juncea, when
      this bacterial strain was inoculated. DISCUSSION: Emendation of B. juncea grown
      in water-filtering beds with a Se(IV)-acclimated microbial community caused a
      higher Se uptake along with a reduction of plant biomass yield with respect to
      plants grown without addition of the same bacterial inoculum. The increase of
      selenium BF in shoots suggests that the Se(IV)-acclimated microbial community not
      only elicited the plant capacity to absorb selenite, but also did improve the
      capacity to transport the metalloid to the epigeous compartments. On the other
      hand, the reduction in plant biomass yield might be related exactly to this
      improved capability of B. juncea to accumulate selenium at concentrations that
      are actually toxic for plants. Differently, addition of two selenite-resistant
      bacterial strains, namely, S. maltophilia SeITE02 and B. mycoides SEITE01, had
      weaker effects on plant biomass production when compared to those recorded in the
      presence of the Se(IV)-adapted microbial community. In particular, inoculation of
      water-filtering beds with the SeITE02 strain alone was the sole strategy
      resulting in a positive effect on both plant biomass production in stressful
      conditions and the capacity of shoots to accumulate selenium. In fact, its
      putative ability of reducing Se(IV) to organo-Se compounds significantly enhanced
      either selenium absorption by the plants or active metalloid translocation to
      epigeous parts. CONCLUSIONS: Bioaugmentation with the bacterial strain S.
      malthophila SeITE02 is suggested to elicit selenite phytoextraction efficiency in
      B. juncea. RECOMMENDATIONS: Manipulation of synergistic interactions between
      plants having phytoextraction capabilities and their associated rhizobacteria may
      enhance already consolidated treatment processes aimed to detoxify selenite laden
      wastewater.

PMID- 19104868
TI  - Substance-related environmental monitoring: Work group 'Environmental Monitoring'
      Position paper.
AB  - BACKGROUND: Due to the requirements of the EU Water Framework Directive and other
      legal regulations (e.g., national laws like the German Federal Soil Protection
      Act), but also due to the implementation of the new EU chemicals management
      system REACH, environmental monitoring will gain increasing importance for the
      surveillance of environmental quality as well as for the assessment of chemicals.
      Against this background, the Work Group on 'Environmental Monitoring' of the
      Division of 'Environmental Chemistry and Ecotoxicology' within the German
      Chemical Society has compiled a position paper on substance-related environmental
      monitoring. SCOPE: Core elements of this position paper are the definitions of
      important terms like monitoring, exposure monitoring, effect monitoring, and
      integrated monitoring. Moreover, temporal and spatial aspects (monitoring of
      spatial distributions, trend monitoring, and retrospective monitoring) and their
      applications are discussed. The main focus of this position paper is the coverage
      of aspects which have to be observed for the preparation and implementation of a
      monitoring program. Essential is the clear specification of the targets of the
      monitoring which determine the development of the monitoring concept and its
      realization, e.g., if environmental media (compartments) or organisms are most
      appropriate as samples for the aim of the study. Of course, also the properties
      of the target substances are important (e.g., lipophilicity/bioaccumulation as
      pre-requisite for an exposure monitoring with organisms). Finally, the monitoring
      phases of sample planning, sampling, storage and transport of samples, selection
      of analytical methods, quality assurance measures as well as reporting are
      discussed. PERSPECTIVES: An important issue for the future is to link the
      quantification of chemicals in environmental compartments (exposure and pollution
      monitoring) more closely to the study of biological effects (effect monitoring)
      than has been the case up to now. Furthermore, by inclusion of a spatial
      differentiation, a comprehensive evaluation of the state of an ecosystem can be
      obtained and the relevance of the results improved. Practical examples of
      monitoring studies which illustrate various aspects covered in this position
      paper will be presented in a series of publications by members of the Work Group
      in the following issues of this journal.

PMID- 19104869
TI  - Use of a food web model to evaluate the factors responsible for high PCB fish
      concentrations in Lake Ellasjoen, a high arctic lake.
AB  - BACKGROUND, AIM, AND SCOPE: Lake Ellasjoen, located in the Norwegian high arctic,
      contains the highest concentrations of polychlorinated biphenyls (PCBs) ever
      recorded in fish and sediment from high arctic lakes, and concentrations are more
      than 10 times greater than in nearby Lake Oyangen. These elevated concentrations
      in Ellasjoen have been previously attributed, in part, to contaminant loadings
      from seabirds that use Ellasjoen, but not Oyangen, as a resting area. However,
      other factors, such as food web structure, organism growth rate, weight, lipid
      content, lake morphology, and nutrient inputs from the seabird guano, also differ
      between the two systems. The aim of this study is to evaluate the relative
      influence of these factors as explanatory variables for the higher PCB fish
      concentrations in Ellasjoen compared with Oyangen, using both a food web model
      and empirical data. METHODS: The model is based on previously developed models
      but parameterized for Lakes Ellasjoen and Oyangen using measured data wherever
      possible. The model was applied to five representative PCB congeners (PCB 105,
      118, 138, 153, and 180) using measured sediment and water concentrations as input
      data and evaluated with previously collected food web data. RESULTS: Modeled
      concentrations are within a factor of two of measured concentrations in 60% and
      40% of the cases in Lakes Ellasjoen and Oyangen, respectively, and within a
      factor of 10 in 100% of the cases in both lakes. In many cases, this is
      comparable to the variability associated with the data as well as the efficacy of
      the predictions of other food web model applications. DISCUSSION: We next used
      the model to quantify the relative importance of five major differences between
      Ellasjoen and Oyangen by replacing variables representing each of these factors
      in the Ellasjoen model with those from Oyangen, in separate simulations. The
      model predicts that the elevated PCB concentrations in Ellasjoen water and
      sediment account for 49%-58% of differences in modeled fish PCB concentrations
      between lakes. These elevated sediment and, to a lesser extent, water
      concentrations in Ellasjoen are due to PCB loadings from seabird guano. However,
      sediment-water fugacity ratios of PCBs are consistently greater in Ellasjoen
      compared with Oyangen, which suggests that internal lake processes also
      contribute to differences in sediment and water concentrations. We hypothesize
      that the nutrients associated with guano influence sediment-water fugacity ratios
      of PCBs by increasing the stock of pelagic algae. As both these algae and the
      guano settle, their organic carbon content is degraded faster than PCBs, which
      causes an extra magnification step in Ellasjoen before these detrital particles
      are consumed by benthic organisms, which are in turn consumed by fish. The model
      predicts that the remaining approximately 50% of the differences in PCB
      concentrations observed between the fish of these lakes are due to other subtle
      differences in their food web structures. CONCLUSIONS: In conclusion, based on
      the results of a food web model, we found that the most dominant factors
      influencing the higher PCB fish concentrations in Lake Ellasjoen compared with
      Oyangen are the higher sediment and water concentrations in Ellasjoen, caused by
      seabird guano. Together, sediment and water are predicted to account for 49%-58%
      of differences in fish concentrations between lakes. Although seabird guano
      provides a source of nutrients to the lake, in addition to contaminants,
      empirical data and indirect model results suggest that nutrients are not leading
      to decreased bioaccumulation, in contrast to what has been observed in temperate,
      pelagic food webs. RECOMMENDATIONS AND PERSPECTIVES: The results of this study
      emphasize the importance of considering even small differences in food web
      structure when comparing bioaccumulation in two lakes; although the food web
      structures of Ellasjoen and Oyangen differ only slightly, the model predicts that
      these differences account for most of the remaining approximately 50% of the
      differences in PCB fish concentrations between the two lakes. This study further
      demonstrates the utility of food web models as we were able to predict and tease
      apart the influence of various factors responsible for the elevated
      concentrations in the fish from Lake Ellasjoen, which would have been difficult
      using the field data alone.

PMID- 19104870
TI  - Weathering patinas on the medieval (S. XIV) stained glass windows of the
      Pedralbes Monastery (Barcelona, Spain).
AB  - BACKGROUND, AIM, AND SCOPE: The first step in the restoration of a medieval
      stained glass window is the evaluation of its degree of degradation. This implies
      the study of the chemical composition of the stained glass as well as the new
      mineral phases developed on its surface (patinas). Patinas are clearly related to
      glass composition, time, environmental conditions, microenvironments developed in
      local zones, bioactivity, physical and chemical factors, etc. This study was
      carried out on patinas developed in selected Na-rich stained glass of the Santa
      Maria de Pedralbes Monastery (Barcelona, Spain). The location of this monument in
      the city (about 5 km from the shoreline and close to the Collserola hill flank)
      helped to determine the environmental conditions in which patinas developed. The
      aim of our study was to characterize the patinas formed on the surface of the
      selected glass of this monastery in order to understand the role of the chemical
      composition of the original glass (Na-rich) as well as the environmental
      conditions in which they developed. MATERIALS AND METHODS: Powdered samples of
      two different color-type patinas (ochre-orange and brownish) were collected in
      the external and internal parts of the stained glass windows of the Prebystery
      and Chapter House of the Pedralbes Monastery by using a precision (odontological)
      drill. These patinas were subsequently analyzed by X-ray diffraction (XRD) and
      Fourier transform infrared spectroscopy (FTIR). RESULTS: XRD analyses evidenced
      the presence of sulfates (gypsum and thenardite), calcite, Ca-oxalates
      (whewellite and weddellite), and quartz forming part of the patinas. Although
      these mineral phases can be found in both color-type patinas, whewellite and
      thenardite are more common in the ochre-orange patinas. The results obtained were
      validated by the FTIR measurements. It has been observed, when thenardite is
      present, that gypsum occurs as traces. Thenardite is in most of the cases
      associated with whewellite and mainly occurs in the internal parts of the glass.
      In contrast, weddellite is limited to the absence of thenardite and whewellite
      and to the external parts of the stained glass. Quartz is present in all the
      patinas independent of their location and color. Calcite also occurs in many
      samples. It appears in both color-type patinas and, in some cases, is associated
      to the presence of weddellite but not to whewellite and/or thenardite.
      DISCUSSION: Glass composition together with environmental conditions and location
      of the patinas (internal or external parts of the stained glass window), as well
      as the provenance of the glass within the monastery, are the main factors that
      define the development of the new mineral phases. Moreover, the action of
      microorganisms, when present, can also strongly influence the development of some
      mineral phases. For example, the formation of calcite in the external parts of
      the stained glass (associated with the presence of oxalates) is related to the
      action of microorganisms. When calcite is formed in the internal parts of the
      glass and it is not associated with the presence of Ca-oxalates, an inorganic
      origin can be invoked. The presence of weddellite requires a very humid
      microenvironment with very little exposure to sunlight. In fact, this mineral
      phase has only been observed in the external parts of some glass located in the
      humid and shady side of the monastery. Whewellite (which only appears in the
      internal parts) needs a low degree of relative humidity. It has been observed
      that sulfur precipitating in basically one mineral phase (thenardite or gypsum)
      depends on the microenvironmental conditions of the moment and the glass
      composition. When thenardite occurs, it can be maintained that the original glass
      is of Na composition. The occurrence of quartz in all samples is interpreted as
      being due to the deposition of atmospheric particulate matter. The color of the
      patinas can be originated by different processes (presence of carotenes, organic
      pigmentation, atmospheric contamination, etc.). CONCLUSIONS: In the case of
      moderately weathered stained glass windows, the combination of XRD and FTIR
      techniques is very useful to obtain a fast preliminary evaluation of the degree
      of weathering of a stained glass window. The presence of specific mineral phases
      in the patina (e.g., thenardite) confirms the Na composition of the original
      stained glass. This is important since Na-rich glass underwent a lesser degree of
      weathering than K- or K-Ca-rich glass. However, their absence cannot preclude
      other possibilities. It has been extensively evidenced through time that
      environmental conditions play an important role on the formation of the different
      mineral phases which form part of the patinas. RECOMMENDATIONS AND PERSPECTIVES:
      The first step in the restoration of a stained glass window is the evaluation of
      the degree of deterioration of the glass. This evaluation includes a chemical
      analysis of the glass as well as a characterization of the patinas developed on
      their surfaces. The obtained results will be essential in order to define the
      best restoration practices to be followed.

PMID- 19104871
TI  - An Egyptian perspective: Man, environment and the ruptured buffer.

PMID- 19104872
TI  - European Topic Centre on Catalogue of Data Sources (ETC/CDS): access to
      environmental information.

PMID- 19104873
TI  - Dioxins in the Venice lagoon: Present situation, projects and recovering
      hypotheses.
AB  - Venice is famous around the world for its uniqueness and architectural
      splendours, arts and the history of the "Serenissima Repubblica", as it was known
      in the past, but few are aware that Venice economy is strongly dependent on the
      industrial activities based mainly on the adjacent Porto Marghera area. For many
      years, the lagoon that physically separates the city from the dry land has
      avoided association between the concern connected with the pollution derived from
      these industrial activities and the public perception of Venice. Since 1995,
      dioxins have appeared as a lagoon contaminant, and their presence, at such a
      level requiring immediate "in depth" studies and interventions, has been fully
      realized for decades.

PMID- 19104874
TI  - Cellobiose dehydrogenase-dependent biodegradation of polyacrylate polymers by
      Phanerochaete chrysosporium.
AB  - When Phanerochaete chrysosporium was cultured using conditions which promote the
      expression of cellobiose dehydrogenase (CDH), but not the ligninolytic
      peroxidases, the fungus effectively solubilized and mineralized an insoluble,
      crosslinked polyacrylate and an insoluble polyacrylate/polyacrylamide copolymer.
      Addition of iron to the cultures increased CDH activity in the cultures and the
      rate and extent of solubilization and mineralization of both polymers.
      Solubilization of both polymers was observed when incubated with purified CDH,
      ferric iron and hydrogen peroxide.

PMID- 19104875
TI  - Data ranges in aquatic toxicity of chemicals: Consequences for environmental risk
      analysis.
AB  - A significant problem for effect assessment of aquatic ecosystems arises from the
      large ranges of toxicity data, which can be found in different databases and
      literature. Here, ranges are given for the aquatic toxicity of 27 high production
      volume chemicals. Based on these illustrative examples and on the current
      literature on uncertainty in aquatic effect assessment, toxicity ranges are
      discussed for their possible causes (variation in experimental condition,
      species, endpoint, time) and ways to handle them (safety factors). Implications
      and recommendations on the procedure of risk analysis of chemical substances are
      drawn. Two main requirements for a comprehensive risk assessment are identified,
      which often play a minor role in current practice (as they are often neglected)
      as well as in scientific discussion (as they are meant to be trivial). First,
      data quality must be checked critically before applying any result of a toxicity
      test. Secondly, experimental data should take into account different species and
      acute as well as chronic data. If these aspects are considered in risk analysis,
      which is common practice in ecotoxicology but not always in the context of
      practical applications in risk engineering, a more comprehensive picture of the
      environmental toxicity of a chemical substance can be obtained.

PMID- 19104876
TI  - Report back from the precautionary principle debate held at the third SETAC World
      Congress, Brighton, May 21-25, 2000.

PMID- 19104877
TI  - EU risk assessment guidelines, Part III. Scenario analysis of a Level III
      multimedia model using generic and regional data.
AB  - Regional PECs (Potential Environmental Concentrations) calculated with the
      software EUSES were compared with measured values using different emission and
      environmental distribution scenarios. The environmental data set recommended in
      EUSES (default data set) represents a generic standard region. In different
      scenarios the parameters of the generic region are replaced by concrete values,
      and estimated parameters (emissions, degradation rates and partition
      coefficients) are substituted by measured or investigated values. Deviations with
      regard to the measured values can be up to three orders of magnitude. Despite the
      basically conservative approximations, underestimations can occur. However, these
      are usually due to poor monitoring data or inappropriate input values. The use of
      regional data instead of default parameters only slightly ameliorates the
      results. The use of real emission and degradation rates alone can improve the
      results significantly.

PMID- 19104878
TI  - Cell bioassays for detection of aryl hydrocarbon (AhR) and estrogen receptor (ER)
      mediated activity in environmental samples.
AB  - In vitro cell bioassays are useful techniques for the determination of receptor
      mediated activities in environmental samples containing complex mixtures of
      contaminants. The cell bioassays determine contamination by pollutants that act
      through specific modes of action. This article presents strategies for the
      evaluation of aryl hydrocarbon receptor (AhR)-(hereafter referred as dioxin-like)
      or estrogen receptor (ER)-mediated activities of potential endocrine disrupting
      compounds (EDCs) in complex environmental mixtures. Extracts from various types
      of environmental or food matrices can be tested by this technique to evaluate
      their 2,3,7,8-tetrachlorodibenzop-dioxin equivalents (TCDD-EQs) or estrogenic
      equivalents (E(2)-EQs) and to identify contaminated samples that need further
      investigation using resource-intensive instrumental analyses. Fractionation of
      sample extracts exhibiting significant activities, and subsequent reanalysis with
      the bioassays can identify important classes of contaminants that are responsible
      for the observed activity. Effect-directed chemical analysis is performed only
      for the active fractions to determine the responsible compounds. Mass-balance
      estimates of all major compounds contributing to the observed effects can be
      calculated to determine if all of the activity has been identified, and to assess
      the potential for interactions such as synergism or antagonism among contaminants
      present in the complex mixtures. The bioassay approach is an efficient (fast and
      cost effective) screening system to identify the samples of interest and to
      provide basic information for further analysis and risk evaluation.

PMID- 19104879
TI  - EPA - Draft dioxin reassessment.

PMID- 19104880
TI  - Passenger aircraft cabin air quality: Trends, effects, societal costs, proposals.

PMID- 19104881
TI  - SCRAM: A scoring and ranking system for persistent, bioaccumulative, and toxic
      substances for the North American Great Lakes. Part III: Acute and subchronic or
      chronic toxicity.
AB  - In Part I of this series (Snyder: et al., 1999a), the Chemical Scoring and
      Ranking Assessment Model (SCRAM) was introduced. This system produces scores for
      chemicals based on their bioaccumulation potential, environmental persistence,
      and toxicity. In Part II, scoring of the potential for a chemical to persist in
      the environment and bioaccumulate was described (Snyder et al., 1999b). In Part
      III, scoring of chemical toxicity is discussed, including definitions and
      descriptions of effects that are scored, specific scoring instructions, the basis
      for the criteria and scores, and specific conditions or concerns regarding the
      types of data used for scoring. A score for each chemical screened is determined
      from available test data from acute or subchronic and chronic toxicity tests
      conducted on aquatic and terrestrial organisms. Subchronic and chronic human
      health effects, including carcinogenicity, are also considered. Part IV includes
      an evaluation of the performance of the scoring and ranking system (Snyder: et
      al., 1999c).

PMID- 19104882
TI  - Effects of dietary carotenoids on mouse lung genomic profiles and their
      modulatory effects on short-term cigarette smoke exposures.
AB  - Male C57BL/6 mice were fed diets supplemented with either beta-carotene (BC) or
      lycopene (LY) that were formulated for human consumption. Four weeks of dietary
      supplementations results in plasma and lung carotenoid (CAR) concentrations that
      approximated the levels detected in humans. Bioactivity of the CARs was
      determined by assaying their effects on the activity of the lung transcriptome
      (~8,500 mRNAs). Both CARs activated the cytochrome P450 1A1 gene but only BC
      induced the retinol dehydrogenase gene. The contrasting effects of the two CARs
      on the lung transcriptome were further uncovered in mice exposed to cigarette
      smoke (CS) for 3 days; only LY activated ~50 genes detected in the lungs of CS
      exposed mice. These genes encoded inflammatory-immune proteins. Our data suggest
      that mice offer a viable in vivo model for studying bioactivities of dietary CARs
      and their modulatory effects on lung genomic expression in both health and after
      exposure to CS toxicants.

PMID- 19104884
TI  - American Academy of Dental Sleep Medicine continuing education offerings.

PMID- 19104883
TI  - Modelling tissues in 3D: the next future of pharmaco-toxicology and food
      research?
AB  - The development and validation of reliable in vitro methods alternative to
      conventional in vivo studies in experimental animals is a well-recognised
      priority in the fields of pharmaco-toxicology and food research. Conventional
      studies based on two-dimensional (2-D) cell monolayers have demonstrated their
      significant limitations: the chemically and spatially defined three-dimensional
      (3-D) network of extracellular matrix components, cell-to-cell and cell-to-matrix
      interactions that governs differentiation, proliferation and function of cells in
      vivo is, in fact, lost under the simplified 2-D condition. Being able to
      reproduce specific tissue-like structures and to mimic functions and responses of
      real tissues in a way that is more physiologically relevant than what can be
      achieved through traditional 2-D cell monolayers, 3-D cell culture represents a
      potential bridge to cover the gap between animal models and human studies. This
      article addresses the significance and the potential of 3-D in vitro systems to
      improve the predictive value of cell-based assays for safety and risk assessment
      studies and for new drugs development and testing. The crucial role of tissue
      engineering and of the new microscale technologies for improving and optimising
      these models, as well as the necessity of developing new protocols and analytical
      methods for their full exploitation, will be also discussed.

PMID- 19104885
TI  - Report on the 3rd International Symposium on Dental Sleep Medicine of the
      European Academy of Dental Sleep Medicine (EADSM), Berlin, 3-4 October 2008.

PMID- 19104886
TI  - Fever: to treat or not to treat?

PMID- 19104887
TI  - Neonatal nutrition: a brief review.
AB  - BACKGROUND: With increasing survival of extremely premature infants, emphasis is
      now focused on the quality of these survivors' lives. Possibly the most important
      factor in the premature's ability to survive in the NICU and thrive is the
      ability to replicate in utero growth through enteral and parenteral nutrition.
      DATA SOURCES: Current literature and review articles were retrieved from PubMed
      and personal files of the authors. RESULTS: The use and complications of the
      various components of total parenteral nutrition (TPN) were reviewed. The
      composition of appropriate enteral feeds for the premature was reviewed as was
      the difficulties associated with the establishment of adequate enteral feeds in
      the premature infants. CONCLUSIONS: Early initiation of amino acids in TPN and
      timely increases in the components of TPN can improve the caloric intake of
      prematures. Enteral feeds, particularly of breast milk, may be started within the
      first few days of life in all but hemodynamically unstable prematures. Newer
      lipid preparations show promise in reversing the hepatic damage of TPN associated
      cholestatic jaundice.

PMID- 19104888
TI  - Efficacy and safety of measles, mumps, rubella and varicella live viral vaccines
      in transplant recipients receiving immunosuppressive drugs.
AB  - BACKGROUND: This review was designed to summarize published data on the efficacy
      and safety of live viral vaccines for measles, mumps, rubella, or varicella in
      post-transplant patients currently on immunosuppression. DATA SOURCES: Medline,
      EMBASE and Evidence Based Medicine Reviews were searched from 1966 to November
      2007 for case reports or studies describing the efficacy and/or safety of live
      attenuated measles, mumps, rubella, or varicella vaccine in children on
      immunosuppression following solid organ, bone marrow or stem cell
      transplantation. RESULTS: The review identified 6 case series and 2 case reports
      describing 114 solid organ transplant recipients and one case series describing
      27 bone marrow transplant recipients who had received a combined total of 206
      doses of live varicella, measles, mumps, or rubella vaccine while on
      immunosuppression. Post-immunization titers were in the immune range in 109 of
      the 171 situations where they were measured following a single dose of vaccine
      (64%) and in 15 of 22 situations following 2 doses (68%). There were no major
      safety concerns in this small sample. CONCLUSION: There are insufficient
      published data to derive evidence-based guidelines for use of live viral vaccines
      in transplant recipients on immunosuppression but preliminary data on efficacy
      and safety suggest that the use of these live viral vaccines in transplant
      recipients still on immunosuppression could be a reasonable strategy.

PMID- 19104889
TI  - First reference curves of waist circumference for German children in comparison
      to international values: the PEP Family Heart Study.
AB  - BACKGROUND: Waist circumference (WC) is a sensitive marker for abdominal obesity
      in the pediatric age group. However, WC is influenced by age, sex, ethnicity and
      body mass index (BMI), causing difficulties in the selection of the most
      appropriate cut-off value. Considering the lack of reference values in Germany,
      we developed age- and gender-specific WC smoothed reference curves in German
      children, and compared them with reference curves obtained from different
      countries. METHODS: A representative sample of 3531 German children (1788 boys,
      1743 girls) aged 3-11 years participating in the Prevention Education Program
      (PEP) Family Heart Study was studied. WC was measured according to the
      recommendations of the World Health Organization, then age- and sex-specific WC
      reference curves were constructed and smoothed using the LMS method and SPSS 14.0
      for statistical analysis. RESULTS: WC increased with age in both boys and girls.
      Boys had higher values of WC than girls at every age and percentile level. 4.1%
      of the boys and 2.8% of the girls had WC values >97th percentile as compared to
      6.3% of the boys and 4.9% of the girls with >97th percentile of BMI (severe
      obesity). 3.1% of the boys and 2% of the girls had both risk factors. Because
      85.3% of the boys and 87.3% of the girls with WC<90th percentile had normal
      weight, this cut-off point might be appropriate for defining high WC.
      CONCLUSIONS: These first WC reference curves of German children can be added to
      the existing international curves for children; comparison of different
      populations demonstrated that the German values are in the middle range of the
      curves obtained in different countries. Our findings about significant
      differences between the reference curves obtained in various regions emphasize
      the necessity of developing population-specific percentiles, and to use them in
      clinical and epidemiological studies among children.

PMID- 19104890
TI  - Asthma School Program in children and their parents.
AB  - BACKGROUND: This study was undertaken to analyze the clinical efficiency of
      Asthma Education Intervention (AEI, Asthma School) in children and their parents,
      a program was designed to produce acceptable asthma knowledge and to improve the
      treatment. METHODS: This study assessed the effectiveness of an educational
      intervention within 12 months after attending Asthma School. The study was
      designed as a population based cohort study. The project endorsed by the European
      Respiratory Society (ERS) Educational Grant was launched in 2004 and finished in
      2006, but the Asthma School continued working. Three hundred and two asthmatics
      recruited during hospital treatment of acute asthma exacerbation completed the
      study together with their parents. The intervention group of 231 asthmatics
      received full Asthma School program. The non-intervention group enrolled 71
      asthmatics receiving usual instructions for asthma management. Clinical and
      educational outcomes were investigated immediately after completion of the
      program and 12 months later. RESULTS: Significant achievements were found in the
      intervention group in asthma knowledge (baseline score 63%, 82% after 12 months,
      P<0.05), compliance (70% before, 90% after), and inhalation technique (20%
      before, 70% after). No change was found in the attitude and behavior regarding
      asthma prognosis in adolescent patients and parents. CONCLUSION: This study
      together with others clearly confirm the effectiveness of educational
      intervention for childhood asthma.

PMID- 19104891
TI  - Lymphocytes in peripheral blood and thyroid tissue in children with Graves'
      disease.
AB  - BACKGROUND: This study was undertaken to analyze subsets of lymphocytes in
      peripheral blood in the early phase and in the thyroid tissue in the late phase
      of Graves' disease (GD) in children. METHODS: The study included 30 children with
      GD and 30 healthy children. Monoclonal antibodies were used to define peripheral
      blood lymphocyte subsets and they were analyzed using the flow cytometer Ortho
      Diagnostic System. After thyroidectomy, T cells were detected by CD3, CD4, CD8
      antibodies, B cells by CD79alpha antibodies, and the antigen presenting dendritic
      cells (APCs) by CD1alpha antibodies (DakoCytomation) in the thyroid tissue.
      RESULTS: Before the treatment, an increased percentage of CD4+ T helper cells and
      B cells and decreased CD8+ T suppressor/cytotoxic cells were observed in
      peripheral blood in all the GD children. The number of lymphocytes and dendritic
      cells in the thyroid tissue increased in the children with GD in comparison to
      the control group, especially T cells subsets CD4+ and CD8+ and CD79alpha+ B
      cells. The percentage of T cells in the thyroid tissue was lower and that of B
      cells was higher than in peripheral blood. In their structure, thyrocytes can
      have components similar to alpha-chains connected with beta-microglobulins, which
      were characteristic for APCs. CONCLUSIONS: The primary defect of immunoregulation
      in children with GD is probably dependent on a large number and the activity of T
      helper cells and on a small number and hypofunction of T suppressor cells. The
      amount of lymphocytes decreased proportionally to the duration of methimazole
      treatment. The thyrocytes probably can present antigens.

PMID- 19104892
TI  - Clinical and pathological characteristics of Alagille syndrome in Chinese
      children.
AB  - BACKGROUND: Alagille syndrome (AS) is regarded as the most common cause of
      chronic cholestasis in childhood associated with specific phenotypic features in
      western countries. This study was undertaken to investigate the significance of
      AS in Chinese children with chronic cholestasis and to describe its clinical and
      histological features. METHODS: From October 2004 to January 2007, 157 children
      who presented with conjugated jaundice from less than 3 months of age were
      admitted to a tertiary hospital in Shanghai. Investigations of the heart, spine,
      eyes and kidneys were conducted in 13 children who experienced prolonged
      cholestasis beyond 1 year of age after exclusion of biliary atresia and familial
      progressive intrahepatic cholestasis type 1 or 2. In patients with interlobular
      bile duct paucity, AS was diagnosed if 3 or more of the following 5 major
      features were present: cardiac murmur, posterior embryotoxon, butterfly-like
      vertebrae, renal abnormalities and characteristic faces. In patients without
      interlobular bile duct paucity or who did not receive liver biopsy, 4 or more
      features were required for the diagnosis. RESULTS: Of the 13 children, 6 were
      diagnosed with AS at ages ranging from 1 year and 7 months to 3 years and 11
      months. Jaundice was noticed in early infancy and then pruritus developed in all
      the 6 patients, of whom 5 presented with acholic stool and 4 had been
      misdiagnosed as having presumed biliary atresia by hepatobiliary scintigraphy or
      laparoscopic cholangiography. Biochemical examinations demonstrated increased
      concentration of total bile acid and hyperlipidemia. Interlobular bile duct
      paucity was demonstrated histologically in 5 patients who received liver biopsy.
      Vertebral abnormalities, heart murmur, characteristic faces and failure to thrive
      were found in all the 6 patients. Two patients had evidence of renal involvement.
      Micropenis, empty scrotum, and gall stone were seen in 1 patient. CONCLUSION: AS
      is also an important cause of prolonged cholestasis in Chinese children. It is
      difficult to differentiate AS from biliary atresia. Liver biopsy and spine X-ray
      may be helpful in the early detection of AS.

PMID- 19104893
TI  - Psychiatric state of college students with a history of childhood sexual abuse.
AB  - BACKGROUND: Childhood sexual abuse (CSA) seriously influences children's
      psychological status. This study aimed to investigate the relationship between
      CSA and the psychiatric disorders. METHODS: An anonymous and retrospective
      questionnaire survey was carried out in 1307 college students (aged 18-25 years;
      701 females, 606 males) to investigate the participants' CSA experience by means
      of a complete random sampling method. The Symptom Check-List-90 (SCL-90) test was
      used to study the victims' psychiatric aspects. RESULTS: 22.11% (155/701) of the
      female students and 14.69% (89/606) of the male students experienced physical
      and/or non-physical contact CSA before age 18, with a significant difference
      between female and male (P<0.05). And 11.43% (80/701) of the female students and
      7.26% (44/606) of the male students experienced physical contact CSA (P<0.05).
      Most abusers were male and young people, and only a few of them used violence.
      78.7% of the females experienced non-physical contact CSA from strangers, while
      71.3% experienced physical contact CSA from acquaintances. 89.9% of the male
      victims knew the abusers before. Females were more likely than males to
      experience physical contact CSA from members of the family circles. The CSA
      incidence increased with age in females, while 54.7% of the male victims
      experienced CSA from 12 to 16 years. The students who experienced CSA had higher
      SCL-90 scores than those who did not in somatization, obsessive-compulsive,
      interpersonal sensitivity, depression, anxiety, hostility, phobic anxiety,
      paranoid ideation, and psychoticism. The more serious the CSA experience was, the
      higher SCL-90 scores of the psychiatric disorders would be. CONCLUSIONS: CSA is
      not uncommon in adolescents. Girls are more likely to experience CSA than boys.
      About half of the abusers are the victims' close relatives, neighbors and
      teachers; most abusers were male. Personal experience of CSA may seriously affect
      the victims' psychological health.

PMID- 19104894
TI  - Diagnosis and surgical treatment of isolated hypoganglionosis.
AB  - BACKGROUND: Some patients suspected with Hirschsprung's disease (HD), however,
      were diagnosed as having isolated hypoganglionosis according to the updated
      pathohistologic methods. This study was undertaken to investigate the diagnostic
      methods and the therapeutic results of isolated hypoganglionosis in children.
      METHODS: A retrospective analysis was made on 17 patients with isolated
      hypoganglionosis (hypoganglionosis group) identified pathologically after
      operation. The data included clinical presentations, barium enema, anorectal
      manometry, histochemical staining for acetylcholinesterase (AChE) before
      operation, histological results after operation and follow-up outcomes. The data
      of hypoganglionosis with HD (HD group) were compared retrospectively. RESULTS:
      Common complaint of the patients with hypoganglionosis and HD was intractable
      constipation. Barium enema showed typical narrowing and distended segment of the
      colon in 9 patients in the hypoganglionosis group (9/16) and in 15 patients in
      the HD group (15/18). In the hypoganglionosis group, in 15 patients who underwent
      anorectal manometry only 5 showed absent rectal anal inhibitory reflex,
      significantly lower than the rate in the HD group (17/18) (P<0.05). From 16
      patients in hypoganglionosis group, positive staining for AChE was noted in 3
      patients (3/16, 18.8%), significantly lower than that in the HD group (16/18,
      88.9%) (P<0.05). Thirteen patients in the hypoganglionosis group received
      subtotal colectomy, while only 5 patients needed subtotal colectomy in the HD
      group. In the hypoganglionosis group, except 2 patients who suffered from mild
      enterocolitis after operation and recovered after conservative therapy, all
      patients recovered uneventfully without wound dehiscence, intestinal fistula,
      fecal incontinence or constipation recurrence. In the HD group, one patient
      suffered from anastomotic leak and got secondary operation, one patient had
      anastomotic stricture at 1 year after operation and recovered by dilatation, and
      other three patients suffered from mild enterocolitis after operation and
      recovered after conservative therapy. CONCLUSIONS: Hypoganglionosis is a common
      disease, and could be finally confirmed by full-thickness biopsies in different
      bowel segments. The resection range can be estimated according to barium enema
      and 24-hour delayed X-ray findings, by which the satisfactory result in short
      term follow-up can be obtained.

PMID- 19104895
TI  - Neonatological and pulmonological management of bilateral pulmonary sequestration
      in a neonate.
AB  - BACKGROUND: Bronchopulmonary sequestration is a lung malformation characterized
      by nonfunctioning lung tissue without primary communication with the
      tracheobronchial tree. Intrauterine complications such as mediastinal shift,
      pleural effusion or fetal hydrothorax can be present. We present the case of a
      newborn with bilateral intralobar pulmonary sequestration. METHODS: Prenatal
      ultrasonography in a primigravida at 20 weeks of gestation revealed echogenic
      masses in the right fetal hemithorax with mediastinal shift towards the left
      side. Serial ultrasound confirmed persistence of the lesion with otherwise
      appropriate fetal development. Delivery was uneventful and physical examination
      revealed an isolated intermittent tachypnea. Chest CT scan and CT angiography
      showed a bilateral intrathoracic lesion with arterial supply from the aorta. Baby
      lung function testing suggested possible multiple functional compartments.
      RESULTS: Right and left thoracotomy was performed at the age of 7 months. A
      bilateral intralobar sequestration with vascularisation from the aorta was
      resected. Pathological and histological examination of the resected tissue
      confirmed the surgical diagnosis. At the age of 24 months, the child was doing
      well without pulmonary complications. CONCLUSIONS: Bilateral pulmonary
      sequestration requires intensive prenatal and postnatal surveillance. Though
      given the fact of a bilateral pulmonary sequestration, postnatal outcome showed
      similar favourable characteristics to an unilateral presentation. Baby lung
      function testing could provide additional information for optimal postnatal
      management and timing of surgical intervention.

PMID- 19104896
TI  - Typhoid sigmoid colon perforation in an 18-month-old boy.
AB  - BACKGROUND: Typhoid fever is a severe infective disease endemic in the areas
      where sanitation is poor. Its serious complication is bowel perforation with
      terminal ileum as the commonest perforation site. We report a case of an
      extremely unusual site of perforation in sigmoid colon due to typhoid fever.
      METHODS: An 18-month-old boy presented with no passage of flatus and feces along
      with guarding and rigidity. Exploratory laparotomy revealed sigmoid colon
      perforation and Widal test was strongly positive for typhoid fever. Sigmoid loop
      colostomy was performed on the patient. RESULTS: Postoperative period was
      uneventful. Colostomy started functioning on the 4th post-operative day. There
      was superficial wound dehiscence. The patient was given oral food intake on the
      7th post-operative day. He was discharged from the hospital in satisfactory
      conditions on the 10th day after operation. CONCLUSIONS: While tackling a case of
      enteric perforation suspected with typhoid fever, one should keep in mind the
      extremely rare site of sigmoid colon perforation.

PMID- 19104897
TI  - Ruptured pseudoaneurysm of the profunda femoris artery due to pellet injury:
      endovascular treatment by coil embolization.

PMID- 19104898
TI  - Cryoplasty for occlusive disease of the femoropopliteal arteries: 1-year follow
      up.
AB  - Atherosclerosis of femoropopliteal arteries is an important cause of morbidity
      and mortality. Percutaneous transluminal angioplasty (PTA) has only limited
      success in treating these arteries, mainly because of the high rate of recurrent
      stenosis. Cryoplasty has been proposed as a technique which might improve
      treatment outcome. This study reports our single-center experience with
      cryoplasty. Thirty-two claudicants, 33 arteries, in whom conservative therapy
      failed, were consecutively included. Duplex ultrasound (US), angiography, and
      ankle-brachial index (ABI) measurement were performed before the procedure; ABI
      and duplex US, 2 weeks and 3, 6, and 12 months after the procedure. Patients'
      symptoms were categorized according to the Rutherford classification. Lesions
      were classified as TASC A, B, or C according to angiographic appearance.
      Differences in ABI before and after the procedure were defined as significant at
      p < 0.05 by paired t-test. Patency was evaluated using duplex US by determining
      the peak systolic velocity ratio. Sixteen TASC A lesions, 13 TASC B lesions, and
      4 TASC C lesions were included. ABI improved significantly for TASC A lesions 2
      weeks and 3 months postprocedure. Patency after 2 weeks, 6 months, and 12 months
      was 93%, 67%, and 64% for TASC A lesions, 83%, 31%, and 31% for TASC B lesions,
      and 100%, 50%, and 33% for TASC C lesions, respectively. In conclusion,
      cryoplasty has good immediate success rates and patency rates similar to the
      results of conventional PTA in the literature.

PMID- 19104899
TI  - Hospital organization and importance of an interventional radiology inpatient
      admitting service: Italian single-center 3-year experience.
AB  - In June 2005 a Complex Operating Unit of Interventional Radiology (COUIR),
      consisting of an outpatient visit service, an inpatient admitting service with
      four beds, and a day-hospital service with four beds was installed at our
      department. Between June 2005 and May 2008, 1772 and 861 well-screened elective
      patients were admitted to the inpatient ward of the COUIR and to the Internal
      Medicine Unit (IMU) or Surgery Unit (SU) of our hospital, respectively, and
      treated with IR procedures. For elective patients admitted to the COUIR's
      inpatient ward, hospital stays were significantly shorter and differences between
      reimbursements and costs were significantly higher for almost all IR procedures
      compared to those for patients admitted to the IMU and SU (Student's t-test for
      unpaired data, p < 0.05). The results of the 3-year activity show that the
      activation of a COUIR with an inpatient admitting service, and the better
      organization of the patient pathway that came with it, evidenced more efficient
      use of resources, with the possibility for the hospital to save money and obtain
      positive margins (differences between reimbursements and costs). During 3 years
      of activity, the inpatient admitting service of our COUIR yielded a positive
      difference between reimbursements and effective costs of 1,009,095.35 euros. The
      creation of an inpatient IR service and the admission of well-screened elective
      patients allowed short hospitalization times, reduction of waiting lists, and a
      positive economic outcome.

PMID- 19104900
TI  - Inguinofemoral lymphadenectomy: randomized trial comparing inguinal skin access
      above or below the inguinal ligament.
AB  - BACKGROUND: Groin wound breakdown, lymphoceles, cellulitis, and chronic leg edema
      are the most frequent complications of inguinal lymphadenectomy, resulting in
      severe patient discomfort and significant lengthening of postoperative stay.
      Despite all innovations, complication rates are still high and inevitable. Our
      experience suggests that cutaneous flap preparation, identification of the Camper
      fascia, and preservation of the most lateral lymphatics decrease associated
      morbidity. The aim of this study is to analyze whether different cutaneous skin
      flap preparations and their different devascularization (above or below the
      inguinal ligament), resecting all the lymphofatty tissue, reduce groin wound
      complications, and whether the same therapeutic approach and number of lymph
      nodes removed are comparable. METHODS: This prospective randomized clinical trial
      of 62 consecutive patients affected by vulvar carcinoma requiring inguinal
      lymphadenectomy compared skin inguinal incision carried out 3-4 cm above the
      inguinal ligament (group A) or below it (group B). RESULTS: Inguinal dehiscence
      was present in 17 of 53 (32.1%) patients in group B and in 9 of 54 (16.7%) in
      group A (P=0.10). Lymphocele was observed in 10 of 53 lymphadenectomies (18.9%)
      in group B and in 3 of 54 dissections (5.6%) in group A (P=0.07). Upper incision
      allows more precise identification of the Camper fascia, is less painful, and
      gives better cosmetic results. Moreover, there may be advantage, albeit not
      statistically significant, regarding flap length, wound dehiscence rate, and
      speed of wound healing. There was no difference in chronic leg edema, number of
      nodes removed, or hospital stay.

PMID- 19104901
TI  - The floating lunate: arthroscopic treatment of simultaneous complete tears of the
      scapholunate and lunotriquetral ligaments.
AB  - Carpal instabilities continue to be a controversial topic in hand surgery.
      Accurate diagnosis of the ligament injuries is usually difficult without an
      arthroscopic evaluation. Few studies have focused on the diagnosis and proper
      management of simultaneous scapholunate (SL) and lunotriquetral (LT) ligament
      tears. This is an uncommon injury that leads to marked disability and chronic
      wrist pain. This is essentially a "floating lunate" and indicates a severe
      ligamentous lesion. Thirteen patients (six female and seven male) with complete
      SL and LT tears and with gross arthroscopic dynamic carpal instability were
      included in the present study. None of the patients showed radiographic evidence
      of lunate dislocation. One patient presented acutely and was operated on 3 days
      after the injury. The average time from the initial injury to the arthroscopy for
      the other 12 patients was 13.5 months (range 1.5-84 months). All patients
      underwent arthroscopic debridement of the SL and LT ligaments coupled with
      percutaneous pinning (two 0.045-in. Kirschner wires) in both joints. At the final
      follow-up, the average range of motion was 50 degrees of flexion, 54 degrees of
      extension, 77 degrees of pronation, 80 degrees of supination, 25 degrees of ulnar
      deviation, and 15 degrees of radial deviation. The average final grip strength
      was 67% from the non-affected side. All patients had negative shifting tests at
      final follow-up. Furthermore, there was no evidence of any static or dynamic
      instability in all the patients except for one patient who developed a volar
      intercalated segment instability 8 months after the surgery. At the final follow
      up, ten patients had no pain, one had mild pain, and two experienced moderate
      pain.

PMID- 19104902
TI  - Scholarship opportunities for trainees and clinician educators: learning outcomes
      from a case report writing workshop.
AB  - INTRODUCTION: Publishing a case report demonstrates scholarly productivity for
      trainees and clinician-educators. AIM: To assess the learning outcomes from a
      case report writing workshop. SETTING: Medical students, residents, fellows and
      clinician-educators attending a workshop. PROGRAM DESCRIPTION: Case report
      writing workshop conducted nine times at different venues. PROGRAM EVALUATION:
      Before and after each workshop, participants self-rated their perceived
      competence to write a case report, likelihood of submitting a case report to a
      meeting or for publication in the next 6-12 months, and perceived career benefit
      of writing a case report (on a five-point Likert scale). The 214 participants
      were from 3 countries and 27 states or provinces; most participants were trainees
      (64.5 %). Self-rated competence for writing a case report improved from a mean of
      2.5 to 3.5 (a 0.99 increase; 95% CI, 0.88-1.12, p < 0.001). The perceived
      likelihood of submitting a case report, and the perceived career benefit of
      writing one, also showed statistically significant improvements (p = 0.002, p =
      0.001; respectively). Nine of 98 participants published a case report 16-41
      months after workshop completion. DISCUSSION: The workshop increased
      participants' perception that they could present or publish a case report.

PMID- 19104903
TI  - Debate: Resection for early hepatocellular carcinoma.
AB  - The management of patients with cirrhosis and early hepatocellular carcinoma
      (HCC) meeting the Milan criteria is controversial. Although liver transplantation
      for early HCC has been shown to have excellent long term survival rates and low
      recurrence rates, its application is limited by organ availability. Hepatic
      resection is an alternative therapy for early HCC. Hepatic resection can be
      performed safely in patients with early HCC and well-compensated cirrhosis. In
      addition, the reported 5-year survival rates are in the range of 50%. Resection
      may also allow a better understanding of tumor biology through pathologic
      examination of the specimen while also providing a potentially curative
      therapeutic option. The management of patients with early HCC is complex.
      Resection should not be viewed as opposing transplantation. Rather, hepatic
      resection should be seen as complementary to transplantation. The best
      therapeutic strategies for patients with early HCC and well-compensated cirrhosis
      should be dependent on the individual clinical situation, not adherence to
      dogmatic universal adoption of either resection or transplantation.

PMID- 19104904
TI  - 3D-MSCT gastric pouch volumetry in bariatric surgery-preliminary clinical
      results.
AB  - BACKGROUND: Insufficient weight loss or persistent abdominal complaints are
      reasons for revisionary operations in bariatric surgery. The selection of the
      secondary procedure is influenced by clinical and by patho-anatomical factors
      like the size of the gastric pouch. The purpose of this study was to evaluate
      multi-slice computed tomography (MSCT)-based volumetric assessment of gastric
      pouches, gastric sleeves, and anastomoses in patients after bariatric surgery.
      METHODS: Twenty-six patients after bariatric surgery received abdominal MSCT
      immediately after oral administration of an ionic contrast agent solution and
      intravenous administration of buthylscopalamine. Indications were insufficient
      weight loss after primary operation, persistent upper abdominal complaints, and
      decline of bariatric analysis and reporting outcomes system (BAROS) score. The
      gastric volumes, diameter of the gastrojejunostomy, and the proximal part of the
      Roux limb were measured on volume rendering images and freely angulated
      reformations. RESULTS: Evaluation of gastric volumes was successful in 25
      examinations (96%). The diameters of gastrojejunostomy as well as the dimensions
      of the Roux limb were evaluable in all cases. After gastric bypass surgery, a
      pouch volume >30 ml was found in ten, a widening of the gastrojejunostomy in
      eight, and a dilated Roux limb in six cases. Two patients presented a combination
      of a wide anastomosis and a strongly dilated Roux limb. Patients after
      biliopancreatic diversion had gastric volumes between 210 and 840 ml. Other
      findings were a fistula, an intragastral stenosis, and internal hernias.
      CONCLUSIONS: MSCT allows crucial patho-anatomical measurements and provides
      helpful information for selecting the appropriate revisionary operation after
      bariatric surgery.

PMID- 19104905
TI  - PPAR-gamma agonist Azelaoyl PAF increases frataxin protein and mRNA expression:
      new implications for the Friedreich's ataxia therapy.
AB  - Friedreich's ataxia is a neurodegenerative disease due to frataxin deficiency,
      and thus, drugs increasing the frataxin amount are excellent candidates for
      therapy. By screening Gene Expression Omnibus profiles, we identified records
      showing a frataxin response to the peroxisome proliferator-activated receptors
      gamma (PPAR-gamma) agonist rosiglitazone. We decided to investigate the effect of
      the PPAR-gamma agonist Azelaoyl PAF on the frataxin protein and mRNA expression
      profile. We treated human neuroblastoma cells SKNBE and primary fibroblasts from
      skin biopsies from Friedreich's ataxia (FRDA) patients and healthy controls with
      the PPAR-gamma agonist Azelaoyl PAF. We show in this paper for the first time
      that Azelaoyl PAF significantly increases the intracellular frataxin levels by
      twofold in the neuroblastoma cell line SKNBE and fibroblasts from FRDA patients
      and that Azelaoyl PAF increases frataxin protein through a transcriptional
      mechanism. PPAR-gamma agonist Azelaoyl PAF increases both messenger RNA and
      protein levels of frataxin. We hypothesize that PPAR-gamma agonists could play a
      role in the treatment of FRDA, and our results offer the logical bases to further
      investigate the usefulness of this group of agents for the treatment of the FRDA.

PMID- 19104906
TI  - Cross-sectional study of kidney stones by laser-induced breakdown spectroscopy.
AB  - We performed laser-induced breakdown spectroscopy (LIBS) for the in situ
      quantitative estimation of elemental constituents distributed in different parts
      of kidney stones obtained directly from patients by surgery. We did this by
      focusing the laser light directly on the center, shell, and surface of the stones
      to find the spatial distribution of the elements inside the stone. The elements
      detected in the stones were calcium, magnesium, manganese, copper, iron, zinc,
      strontium, sodium, potassium, carbon, hydrogen, nitrogen, oxygen, phosphorus,
      sulfur, and chlorine (Cl), etc. We optimized the LIBS signals by varying the
      laser energy from 10 mJ to 40 mJ to obtain the best signal-to-background and
      signal-to-noise ratios. We estimated the quantities of different elements in the
      stones by drawing calibration curves, plotting graphs of the analyte signal
      versus the absolute concentration of the elements in standard samples. The
      detection limits of the calibration curves were discussed. The concentrations of
      the different elements were found to be widely different in different stones
      found in different age groups of patients. It was observed that stones containing
      higher amounts of copper also possessed higher amounts of zinc. In general, the
      concentrations of trace elements present in the kidney stones decreased as we
      moved from center to shell and surface. Our results also revealed that the
      concentrations of elements present in the stones increased with the age of the
      patients. The results obtained from the calibration curves were compared with
      results from inductively coupled plasma mass spectrometry (ICP-MS). We also used
      the intensity ratios of different elemental lines to find the spatial
      distribution of different elements inside the kidney stones.

PMID- 19104907
TI  - Effect of laser therapy (660 nm) on recovery of the sciatic nerve in rats after
      injury through neurotmesis followed by epineural anastomosis.
AB  - The aim of this study was to analyze the influence of aluminum gallium arsenide
      (AlGaAs) laser (660 nm) on the myelin sheath and functional recovery of the
      sciatic nerve in rats. The sciatic nerves of 12 Wistar rats were subjected to
      injury through neurotmesis and epineural anastomosis, and the animals were
      divided into two groups: group 1 was the control and group 2, underwent low-level
      laser therapy (LLLT). After the injury, AlGaAs laser at 660 nm, 4 J/cm(2), 26.3
      mW and beam area of 0.63 cm(2) was administered to three equidistant points on
      the injury for 20 consecutive days. In the control group the mean area of the
      myelin impairment was 0.51 (+/- 0.11) on day 21 after the operation, whereas this
      value was 1.31 (+/- 0.22) in the LLLT group. Student's t-test revealed a P value
      = 0.0229 for the mean area values of the myelin sheath between the LLLT and
      control groups. Comparison of the sciatic functional index (SFI) showed that
      there was no significant difference between the pre-lesion value in the laser
      therapy group and the control group. The use of AlGaAs laser (660 nm) provided
      significant changes to the morphometrically assessed area of the myelin sheath,
      but it did not culminate in positive results for functional recovery in the
      sciatic nerve of the rats after injury through neurotmesis.

PMID- 19104908
TI  - Adult T-cell leukemia after immunosuppressive therapy for systemic lupus
      erythematosus.

PMID- 19104910
TI  - Liver fatty acid binding protein gene ablation enhances age-dependent weight gain
      in male mice.
AB  - Although studies performed in vitro and with transfected cells in culture suggest
      a role for liver fatty acid binding protein (L-FABP) in regulating fatty acid
      oxidation and fat deposition, the physiological significance of this possibility
      is not completely clear. To begin to address this question, the effect of L-FABP
      gene ablation on phenotype of standard rodent chow-fed male mice was examined
      with increasing age up to 18 months. While young (2-3 months old) L-FABP null
      mice displayed no visually obvious phenotype, with increasing age >9 months the L
      FABP null mice were visibly larger, exhibiting increased body weight due to
      increased fat and lean tissue mass. Liver lipid concentrations were unaffected by
      L-FABP gene ablation with the exception of triacylglycerol, which was decreased
      by 74% in the livers of 3-month-old mice. Likewise, serum lipid levels were not
      altered in L-FABP null mice with the exception of triacylglycerol, which was
      increased in the serum of 18-month-old mice. Increased body weight, fat tissue
      mass, and lean tissue mass in 18-month-old L-FABP null mice were accompanied by
      increased hepatic levels of low-density lipoprotein (LDL) receptor, peroxisome
      proliferator-activated receptor (PPAR) alpha, and PPARalpha-regulated proteins
      such as fatty acid transport protein (FATP), fatty acid translocase (FAT/CD36),
      carnitine palmitoyl transferase I (CPT I), and lipoprotein lipase (LPL). A key
      enzyme in cholesterol biosynthesis, 3-hydroxy-3-methylglutaryl Coenzyme A (HMG
      CoA) reductase, was down-regulated in L-FABP null mice. These findings were
      consistent with a proposed role for L-FABP as an important physiological
      regulator of PPARalpha.

PMID- 19104909
TI  - NPRA-mediated suppression of AngII-induced ROS production contribute to the
      antiproliferative effects of B-type natriuretic peptide in VSMC.
AB  - Excessive proliferation of vascular smooth cells (VSMCs) plays a critical role in
      the pathogenesis of diverse vascular disorders, and inhibition of VSMCs
      proliferation has been proved to be beneficial to these diseases. In this study,
      we investigated the antiproliferative effect of B-type natriuretic peptide (BNP),
      a natriuretic peptide with potent antioxidant capacity, on rat aortic VSMCs, and
      the possible mechanisms involved. The results indicate that BNP potently
      inhibited AngiotensinII (AngII)-induced VSMCs proliferation, as evaluated by
      [(3)H]-thymidine incorporation assay. Consistently, BNP significantly decreased
      AngII-induced intracellular reactive oxygen species (ROS) and NAD(P)H oxidase
      activity. 8-Br-cGMP, a cGMP analog, mimicked these effects. To confirm its
      mechanism, siRNA of natriuretic peptide receptor-A(NRPA) strategy technology was
      used to block cGMP production in VSMCs, and siNPRA attenuated the inhibitory
      effects of BNP in VSMCs. Taken together, these results indicate that BNP was
      capable of inhibiting VSMCs proliferation by NPRA/cGMP pathway, which might be
      associated with the suppression of ROS production. These results might be
      related, at least partly, to the anti-oxidant property of BNP.

PMID- 19104911
TI  - Alterations in the expression of myocardial calcium cycling genes in rats fed a
      low protein diet in utero.
AB  - An adverse environmental experience of the growing fetus leads to permanent
      changes in the structure and contractile function of the heart; however, the
      mechanisms are incompletely understood. To examine if a maternal low protein (LP)
      diet can modulate the gene and protein expression of the Ca(2+)-cycling proteins
      in the neonatal heart, we employed a rat model in which pregnant dams were fed
      diets containing either 180 (normal) or 90 g (low) casein/kg diet for 2 weeks
      before mating and throughout pregnancy. A significant reduction in the L-type
      Ca(2+)-channel mRNA level in the LP group was detected at 1, 7, and 14 days of
      age. Although ryanodine receptor (RyR) mRNA levels progressively declined in the
      aging heart in both groups, the RyR mRNA levels were consistently higher in the
      LP group. A reduction in RyR protein content was seen only in the hearts of the
      LP group at 7 days of age. The Na(+)-Ca(2+)-exchanger (NCX) mRNA level was also
      markedly increased at all ages. Although an increase in sarco(endo)plasmic
      reticulum ATPase 2a (SERCA) 2a mRNA was only detected in the LP group at 7 days
      of age, corresponding protein level was depressed. On the other hand, an initial
      decrease (at 1 day of age) followed by an increase (at 14 and 28 days of age) in
      phospholamban (PLB) mRNA levels was detected. Although PLB protein level was also
      depressed at 1 day of age in the LP group, a marked increase was seen at 7 days
      of age. Moreover, the ratio of serine 16 and threonine 17 phosphorylated PLB to
      non-phosphorylated PLB was reduced at 7 days of age in the hearts of offspring of
      the LP group. These data suggest that maternal LP diet can induce alterations in
      the gene expression and protein levels of the Ca(2+)-cycling proteins in the
      neonatal heart.

PMID- 19104912
TI  - The DNA damage-inducible C. elegans tankyrase is a nuclear protein closely linked
      to chromosomes.
AB  - Tankyrases are protein members of the poly(ADP-ribose) polymerase family bearing
      several ankyrin domain and a WGR domain. They have functional role in telomere
      maintenance, are found at centrosome, and are associated with vesicular
      secretion. This diversity in localization and function makes it difficult to
      identify a unified role for tankyrases. We have shown that the C. elegans
      orthologue PME-5 is among the most transcriptionally up-regulated genes following
      ionizing radiations, linking a tankyrase with DNA damage response. Our analysis
      showed that the up-regulation of PME-5 is translated at the protein level,
      suggesting an effective role in DNA damage response or DNA repair. In order to
      gain more information on the potential role of PME-5 in DNA damage response, we
      analyzed its sub-cellular localization. Using immunostaining as well as gfp
      reporter assay, we have shown a nuclear localization for PME-5. Moreover, we
      showed that PME-5 is a ubiquitous nuclear protein expressed throughout the
      development of the worm and is closely linked to chromatin and condensed
      chromosomes. Taken together, our data suggest that C. elegans can be used to
      study the nuclear roles of tankyrase.

PMID- 19104913
TI  - Hydroxyapatite coating by sol-gel on Ti-6Al-4V alloy as drug carrier.
AB  - In this study Ti-6Al-4V samples were used as substrates and Ca-P layers were
      deposited using sol-gel technique and covered by spin-coating. The efficiency of
      hydroxyapatite (HA) coatings as drug carrier was also evaluated by immersion in
      gentamicin sulphate solution and the release profiles were obtained by cumulative
      method of the coating samples. Three non-linear mathematical methods were
      employed in order to discuss a possible mechanism to lead the drug release.
      Physical chemical techniques showed the presence of the typical absorption bands
      of calcium phosphates by infrared spectroscopy while X-ray diffraction peaks
      matched up with hydroxyapatite patterns. Microstructural techniques (SEM, EDS)
      help to confirm the hydroxyapatite coating by surface aspect and Ca/P ratio
      (1.64). The best fitting according statistical results explained each stage of
      the released profiles and correspond to a mixture of short initial burst effect
      plus drug dissolution with a specific kinetic and the diffusion of the gentamicin
      solid particles.

PMID- 19104914
TI  - Near complete rescue of experimental Parkinson's disease with intravenous, non
      viral GDNF gene therapy.
AB  - PURPOSE: Rats with experimental Parkinson's disease (PD) are treated with
      intravenous glial-derived neurotrophic factor (GDNF) plasmid DNA and non-viral
      gene therapy using Trojan horse liposomes (THLs) targeted with a monoclonal
      antibody (MAb) to the rat transferrin receptor (TfR). The GDNF transgene
      expression is under the influence of the rat tyrosine hydroxylase (TH) promoter.
      METHODS: The GDNF expression plasmid is designated pTHproGDNF. Rats were treated
      with 3 weekly injections of THLs starting 1 week after the intra-cerebral
      injection of 6-hydroxydopamine. The dose of the pTHproGDNF was 10
      mICROg/rat/weekly injection. Rats were tested with three assays of neurobehavior,
      and terminal striatal TH enzyme activity was measured at 6 weeks following toxin
      administration, which is 3 weeks following the last administration of THLs.
      RESULTS: Apomorphine-induced contralateral rotation was reduced 87% by THL gene
      therapy; amphetamine-induced ipsilateral rotation was reduced 90% by THL gene
      therapy; whisker-induced forelimb placement abnormalities were reduced 77% with
      THL gene therapy. The improvement in neurobehavior correlated with a lasting 77%
      increase in striatal TH enzyme activity, relative to saline treated rats.
      CONCLUSIONS: Near complete abrogation of the neurotoxin effects are achieved with
      multiple intravenous dosing of GDNF plasmid DNA gene therapy, using receptor
      targeted THLs, and a region-specific promoter.

PMID- 19104915
TI  - Development of a new predictive model for interactions with human cytochrome P450
      2A6 using pharmacophore ensemble/support vector machine (PhE/SVM) approach.
AB  - PURPOSE: The objective of this investigation was to yield a generalized in silico
      model to quantitatively predict CYP2A6-substrates/inhibitors interactions to
      facilitate drug discovery. METHODS: The newly invented pharmacophore
      ensemble/support vector machine (PhE/SVM) scheme was employed to generate the
      prediction model based on the data compiled from the literature. RESULTS: The
      predictions by the PhE/SVM model are in good agreement with the experimental
      observations for those molecules in the training set (n = 24, r (2) = 0.94, q (2)
      = 0.85, RMSE = 0.30) and the test set (n = 9, r (2) = 0.96, RMSE = 0.29). In
      addition, this in silico model performed equally well for those molecules in the
      external validation sets, namely one set of benzene and naphthalene derivatives
      (n = 45, r (2) = 0.81, RMSE = 0.46) and one set of amine neurotransmitters (n =
      4, r (2) = 0.98, RMSE = 0.32). Furthermore, when compared with crystal
      structures, the calculated results are consistent with the published CYP2A6
      substrate co-complex structure and the plasticity nature of CYP2A6 is also
      revealed. CONCLUSIONS: This PhE/SVM model is an accurate and robust model and can
      be utilized for predicting interactions with CYP2A6, high-throughput screening
      and data mining to facilitate drug discovery.

PMID- 19104916
TI  - Effect of ions on agitation- and temperature-induced aggregation reactions of
      antibodies.
AB  - PURPOSE: The impact of ions on protein aggregation remains poorly understood. We
      explored the role of ionic strength and ion identity on the temperature- and
      agitation-induced aggregation of antibodies. METHODS: Stability studies were used
      to determine the influence of monovalent Hofmeister anions and cations on
      aggregation propensity of three IgG(2) mAbs. The C(H)2 domain melting temperature
      (T (m1)) and reduced valence (z*) of the mAbs were measured. RESULTS: Agitation
      led to increased solution turbidity, consistent with the formation of insoluble
      aggregates, while soluble aggregates were formed during high temperature storage.
      The degree of aggregation increased with anion size (F(-) < Cl(-) < Br(-) < I(-)
      < SCN(-) ~ ClO(4) (-)) and correlated with a decrease in T (m1) and z*. The
      aggregation propensity induced by the anions increased with the chaotropic nature
      of anion. The cation identity (Li(+), Na(+), K(+), Rb(+), or Cs(+)) had no effect
      on T (m1), z* or aggregation upon agitation. CONCLUSIONS: The results indicate
      that anion binding mediates aggregation by lowering mAb conformational stability
      and reduced valence. Our observations support an agitation-induced particulation
      model in which anions enhance the partitioning and unfolding of mAbs at the
      air/water interface. Aggregation predominantly occurs at this interface;
      refreshing of the surface during agitation releases the insoluble aggregates into
      bulk solution.

PMID- 19104917
TI  - The green journey.

PMID- 19104918
TI  - Steady-state and time-resolved fluorescence spectroscopic studies on interaction
      of the N-terminal region with the hairpin loop of the phytocystatin Scb.
AB  - The steady-state and time-resolved fluorescence spectroscopy is one of the most
      powerful method to detect and analyze subtle conformation change and interaction
      between peptide elements in protein. Phytocystatin Scb isolated from sunflower
      seeds includes a single Trp residue at position 85. In an attempt to investigate
      the interaction of the N-terminal region of Scb with the first and second hairpin
      loops by fluorescence spectroscopy of Trp residue, two Scb mutants in which
      single Trp locates at position 52 and 58, respectively, and their N-terminal
      removed mutants were generated. The N-terminal truncation changed the
      fluorescence decay kinetics of Trp52 from the triple exponential to double.
      Furthermore, the time-resolved fluorescence anisotropy residue indicated that the
      segmental motion of Trp52 was significantly enhanced by its N-terminal
      truncation. In contrast, Trp58 and Trp85 had little influence. The N-terminal
      successive truncations of Scb and its mutants resulted in the weaken inhibitors
      to papain. These results suggested that the N-terminal region of Scb interacts
      with the peptide segment preceding the first hairpin loop, thereby stabilizing
      the conformation of the hairpin loop structure.

PMID- 19104919
TI  - Synthesis and characterization of monodispersed SiO2@Y3Al5O12:Er3+ core-shell
      particles.
AB  - Submicron core-shell structure particles SiO2@Y3Al5O12:Er3+, which silica
      spherical particles was coated with an yttrium aluminum garnet (Y3Al5O12) layer
      doped with Er3+, were prepared by the modified Pechini-Type sol-gel method for
      the first time. The structure and morphology of samples were detected by the X
      ray powder diffraction (XRD) measurement, field emission scanning electron
      microscopy (FESEM) and transmission electron microscopy (TEM), respectively. The
      results indicate that well-crystallized garnet nanocrystallines were formed on
      the surface of the silica particles. The luminescent spectra in near infrared and
      visible region of the core-shell structured SiO2@Y3Al5O12:Er3+ powders were also
      investigated and compared with those of the pure Y3Al5O12:Er3+ and the Er3+ doped
      silicate glass. The results show that mono-dispersed SiO2@Y3Al5O12:Er3+ core
      shell spherical particles with the near infrared, red and green luminescent
      emissions under the excitation of 980 nm laser diode have been successfully
      synthesized.

PMID- 19104920
TI  - Thiol-capped CdTe quantum dots with two-photon excitation for imaging high
      autofluorescence background living cells.
AB  - To effectively image living cells with quantum dots (QDs), particularly for those
      cells containing high content of native fluorophores, the two-photon excitation
      (TPE) with a femto-second 800 nm laser was employed and compared with the single
      photon excitations (SPE) of 405 nm and 488 nm in BY-2 Tobacco (BY-2-T) and human
      hepatocellular carcinoma (QGY) cells, respectively. The 405 nm SPE produced the
      bright photoluminescence (PL) signals of cellular QDs but also induced a strong
      autofluorescence(AF) from the native fluorophores like flavins in cells. The AF
      occupied about 30% and 13% of the total signals detected in QD imaging channel in
      the BY-2-T and QGY cells, respectively. With the excitation of 488 nm SPE, the PL
      signals were lower than those excited with the 405 nm SPE, although the AF
      signals were also reduced. The 800 nm TPE generated the best PL images of
      intracellular QDs with the highest signal ratio of PL to AF, because the two
      photon absorption cross section of QDs is much higher than that of the native
      fluorophores. By means of the TPE, the reliable cellular imaging with QDs, even
      for the cells having the high AF background, can be achieved.

PMID- 19104921
TI  - A fluorescent probe for diacetyl detection.
AB  - A water-soluble fluorescent probe, rhodamine B hydrazide (RBH), was prepared and
      its properties for recognition of diacetyl were studied. The method employs the
      reaction of diacetyl with RBH, a colorless and non-fluorescent rhodamine B spiro
      form derivative to give a pink-colored fluorescent substance. In weakly acidic
      media, RBH reacts more selectively with diacetyl than with other carbonyls,
      causing a large increase in fluorescence intensity and thereby providing an easy
      assay for the determination of diacetyl.

PMID- 19104922
TI  - Bio-ecological control of chronic liver disease and encephalopathy.
AB  - Minimal encephalopathy was originally associated with chronic liver disease but
      is increasingly associated with most other chronic diseases and particularly with
      diabetes and also chronic disorders in other organs: kidneys, lungs, thyroid and
      with obesity. It is increasingly with dramatically increased and more or less
      permanent increase in systemic inflammation, most likely a result of Western
      lifestyle. Frequent physical exercise and intake of foods rich in vitamins,
      antioxidants, fibres, lactic acid bacteria etc in combination with reduction in
      intake of refined and processed foods is known to reduce systemic inflammation
      and prevent chronic diseases. Some lactic acid bacteria, especially Lb paracasei,
      lb plantarum and pediococcus pentosaceus have proven effective to reduce
      inflammation and eliminate encephalopathy. Significant reduction in blood ammonia
      levels and endotoxin levels were reported in parallel to improvement of liver
      disease. Subsequent studies with other lactic acid bacteria seem to demonstrate
      suppression of inflammation and in one study also evidence of clinical
      improvement.

PMID- 19104924
TI  - Identifying the direct effects of ammonia on the brain.
AB  - Elevated concentrations of ammonia in the brain as a result of hyperammonemia
      leads to cerebral dysfunction involving a spectrum of neuropsychiatric and
      neurological symptoms (impaired memory, shortened attention span, sleep-wake
      inversions, brain edema, intracranial hypertension, seizures, ataxia and coma).
      Many studies have demonstrated ammonia as a major player involved in the
      neuropathophysiology associated with liver failure and inherited urea cycle
      enzyme disorders. Ammonia in solution is composed of a gas (NH(3)) and an ionic
      (NH(4) (+)) component which are both capable of crossing plasma membranes through
      diffusion, channels and transport mechanisms and as a result have a direct effect
      on pH. Furthermore, NH(4) (+) has similar properties as K(+) and, therefore,
      competes with K(+) on K(+) transporters and channels resulting in a direct effect
      on membrane potential. Ammonia is also a product as well as a substrate for many
      different biochemical reactions and consequently, an increase in brain ammonia
      accompanies disturbances in cerebral metabolism. These direct effects of elevated
      ammonia concentrations on the brain will lead to a cascade of secondary effects
      and encephalopathy.

PMID- 19104925
TI  - Solving the brain synchrony eigenvalue problem: conservation of temporal dynamics
      (fMRI) over subjects doing the same task.
AB  - Brain measures often show highly structured temporal dynamics that synchronize
      when observers are doing the same task. The standard method for analysis of brain
      imaging signals (e.g. fMRI) uses the GLM for each voxel indexed against a
      specified experimental design but does not explicitly involve temporal dynamics.
      Consequently, the design variables that determine the functional brain areas are
      those correlated with the design variation rather than the common or conserved
      brain areas across subjects with the same temporal dynamics given the same
      stimulus conditions. This raises an important theoretical question: Are temporal
      dynamics conserved across individuals experiencing the same stimulus task? This
      general question can be framed in a dynamical systems context and further be
      posed as an eigenvalue problem about the conservation of synchrony across all
      brains simultaneously. We show that solving the problem results in a non
      arbitrary measure of temporal dynamics across brains that scales over any number
      of subjects, stabilizes with increasing sample size, and varies systematically
      across tasks and stimulus conditions.

PMID- 19104923
TI  - Signaling factors in the mechanism of ammonia neurotoxicity.
AB  - Mechanisms involved in hepatic encephalopathy (HE) still remain poorly
      understood. It is generally accepted that ammonia plays a major role in this
      disorder, and that astrocytes represent the principal target of ammonia
      neurotoxicity. In recent years, studies from several laboratories have uncovered
      a number of factors and pathways that appear to be critically involved in the
      pathogenesis of this disorder. Foremost is oxidative and nitrosative stress
      (ONS), which is largely initiated by an ammonia-induced increase in intracellular
      Ca(2+). Such increase in Ca(2+) activates a number of enzymes that promote the
      synthesis of reactive oxygen-nitrogen species, including constitutive nitric
      oxide synthase, NADPH oxidase and phospholipase A2. ONS subsequently induces the
      mitochondrial permeability transition, and activates mitogen-activated protein
      kinases and the transcription factor, nuclear factor-kappaB (NF-kappaB). These
      factors act to generate additional reactive oxygen-nitrogen species, to
      phosphorylate various proteins and transcription factors, and to cause
      mitochondrial dysfunction. This article reviews the role of these factors in the
      mechanism of HE and ammonia toxicity with a focus on astrocyte swelling and
      glutamate uptake, which are important consequences of ammonia neurotoxicity.
      These pathways and factors provide attractive targets for identifying agents
      potentially useful in the therapy of HE and other hyperammonemic disorders.

PMID- 19104926
TI  - Stability and structural constraints of random brain networks with excitatory and
      inhibitory neural populations.
AB  - The stability of brain networks with randomly connected excitatory and inhibitory
      neural populations is investigated using a simplified physiological model of
      brain electrical activity. Neural populations are randomly assigned to be
      excitatory or inhibitory and the stability of a brain network is determined by
      the spectrum of the network's matrix of connection strengths. The probability
      that a network is stable is determined from its spectral density which is
      numerically determined and is approximated by a spectral distribution recently
      derived by Rajan and Abbott. The probability that a brain network is stable is
      maximum when the total connection strength into a population is approximately
      zero and is shown to depend on the arrangement of the excitatory and inhibitory
      connections and the parameters of the network. The maximum excitatory and
      inhibitory input into a structure allowed by stability occurs when the net input
      equals zero and, in contrast to networks with randomly distributed excitatory and
      inhibitory connections, substantially increases as the number of connections
      increases. Networks with the largest excitatory and inhibitory input allowed by
      stability have multiple marginally stable modes, are highly responsive and
      adaptable to external stimuli, have the same total input into each structure with
      minimal variance in the excitatory and inhibitory connection strengths, and have
      a wide range of flexible, adaptable, and complex behavior.

PMID- 19104927
TI  - Competitive replication of different genotypes of infectious bursal disease virus
      on chicken embryo fibroblasts.
AB  - Infectious bursal disease virus (IBDV) causes immunosuppression in chickens. We
      investigated the molecular changes in chicken embryo fibroblasts (CEF) adapted
      IBDV by genomic sequencing. IBDV were serially passaged in CEF and chickens were
      infected with the IBDV obtained after different numbers of passages in CEF.
      Chicken infections showed that 16th, 20th, and 21st passage viruses were
      pathogenic, while 26th and 36th passage viruses were non-pathogenic. Sequencing
      demonstrated that the initial changes during the serial passage comprised of a
      single-nucleotide deletion in the 3' non-coding region of segment B of the virus
      after 19th passage, followed by changes in the VP1 gene after the 20th passage of
      the virus and changes in VP2, VP5 after the 21st passage of the virus. These data
      suggested that the attenuation of very virulent IBDV was due to multigenic
      mutations and there are in vitro and in vivo competitive replications in IBDV
      quasispecies.

PMID- 19104928
TI  - Barriers to adoption of new treatments: an internet study of practicing community
      psychotherapists.
AB  - Over 1,600 North American psychotherapists from a wide range of disciplines and
      practice settings completed an open-ended question on perceived barriers to
      adoption of new treatments as part of an internet survey. Content analysis
      indicated that there were five overall themes: clinician attitudes, client
      characteristics, contextual or institutional factors, training issues and other.
      The most frequently endorsed theme revolved around training issues, particularly,
      insufficient time and cost for training, lack of confidence in mastering the
      technique, and lack of opportunities for refining skills. Specific ideas for
      overcoming these barriers are identified.

PMID- 19104929
TI  - Implementation research in mental health services: an emerging science with
      conceptual, methodological, and training challenges.
AB  - One of the most critical issues in mental health services research is the gap
      between what is known about effective treatment and what is provided to consumers
      in routine care. Concerted efforts are required to advance implementation science
      and produce skilled implementation researchers. This paper seeks to advance
      implementation science in mental health services by over viewing the emergence of
      implementation as an issue for research, by addressing key issues of language and
      conceptualization, by presenting a heuristic skeleton model for the study of
      implementation processes, and by identifying the implications for research and
      training in this emerging field.

PMID- 19104930
TI  - Immunohistochemical validation of multiple phospho-specific epitopes for estrogen
      receptor alpha (ERalpha) in tissue microarrays of ERalpha positive human breast
      carcinomas.
AB  - Estrogen receptor alpha (ERalpha) activity is regulated by phosphorylation at
      several sites. Recently several antibodies specific for individual phosphorylated
      sites within ERalpha have became available. Such antibodies potentially provide
      invaluable tools to gain insight into the relevance in vivo of phosphorylated
      ERalpha in human breast tumors. However, validation of these antibodies for
      immunohistochemistry in particular is necessary in the first instance. In this
      study we have investigated the usefulness of several antibodies generated to
      specific phosphorylated sites within ERalpha for immunohistochemistry of formalin
      fixed, paraffin-embedded human breast cancer biopsy samples. As well, these data
      demonstrate for the first time, the detection of multiple phosphorylated ERalpha
      forms in breast cancer (P-S104/106-ERalpha, P-S118-ERalpha, P-S167-ERalpha, P
      S282-ERalpha, P-S294-ERalpha, P-T311-ERalpha, and P-S559-ERalpha) suggesting the
      possibility that profiling of phosphorylated ERalpha isoforms might be useful in
      selecting subgroups of breast cancer patients that would benefit from endocrine
      therapy.

PMID- 19104931
TI  - Infectious complications in patients with severe acute pancreatitis.
AB  - This study aims to investigate the clinical characteristics of infectious
      complications in severe acute pancreatitis (SAP). From September 2003 to March
      2005, 140 patients with SAP were retrospectively identified. SAP was defined by
      the diagnostic criteria formulated for SAP at the 2002 Bangkok World Congress of
      Gastroenterology in Thailand. Clinical data of the infected and non-infected
      patients was compared and the characteristics of infection were also analyzed.
      There were 44 patients who developed infectious complications with a rate of
      31.4% (44/140). The severity index, the incidence of complications and mortality,
      was significantly higher in the infected patients than in the non-infected
      patients (P<0.05). Of 65 episodes of infection, infected (peri) pancreatic
      necrosis accounted for 47.7% (31/65), pneumonia for 27.7% (18/65), bacteremia for
      10.8% (7/65), urinary tract infection for 6.1% (4/65), and gastrointestinal tract
      infection for 7.7% (5/65). The earliest infection was observed in pneumonia
      (10.7+/-2.5 days), followed by bacteremia (13.7+/-1.5 days), gastrointestinal
      tract infection (16.8+/-3.9 days), infected (peri)pancreatic necrosis (17.6+/-2.9
      days), and urinary tract infection (20.5+/-4.8 days). Gram-negative bacteria were
      preponderantly found, comprising 56.6% (64/113) of the isolated strains. Gram
      positive bacteria and fungus accounted for 22.1% (25/113) and 21.2% (24/113) of
      the isolated strains, respectively. Infectious complications in patients with SAP
      occurred in those who had severe episodes, and consequently complicated the
      clinical courses. Infected (peri)pancreatic necrosis is the most susceptible and
      pneumonia is the earliest. Gram-negative bacteria were predominant in multi
      microorganisms.

PMID- 19104932
TI  - Sociodemographic trends in national ambulatory care visits for hepatitis C virus
      infection.
AB  - Poor and non-white patients are disproportionately infected with the hepatitis C
      virus (HCV). The objective of this research is to determine sociodemographic
      patterns of HCV-related ambulatory care visits over time. Data from the National
      Ambulatory Medical Care Survey (NAMCS) and the National Hospital Ambulatory
      Medical Care Survey-Outpatient (NHAMCS-OPD) for the years 1997-2005 were analyzed
      in 3-year intervals. Demographic and other variables were compared for each
      period, and multivariable logistic regression was performed to examine whether
      the likelihood of a visit being HCV-related (versus non-HCV) was independently
      associated with (1) race and/or (2) Medicaid status over time. The total number
      of HCV-related ambulatory visits more than doubled from 3,583,585 during the
      years 1997-1999 to 8,027,166 during 2003-2005. During this time, the proportion
      of non-whites and Medicaid recipients presenting for HCV-related visits
      approximately doubled (non-whites: 16% vs. 33%, P=0.04; Medicaid recipients: 10%
      vs. 25%, P=0.07). In 2003-2005, HCV-related visits were more than twice as likely
      to occur among non-white patients vs. white patients (OR=2.49; 95% CI: 1.60-3.86)
      and patients on Medicaid vs. non-Medicaid (3.49; 1.79-6.80). Our results show
      that HCV-associated ambulatory care visits are increasing, with a greater
      proportion of visits occurring among non-white patients and Medicaid recipients.

PMID- 19104934
TI  - Comparison of scoring systems for the prediction of outcomes in patients with
      nonvariceal upper gastrointestinal bleeding: a prospective study.
AB  - The authors aimed to compare the clinical utility of five scoring systems for the
      prediction of rebleeding and death in patients with nonvariceal upper
      gastrointestinal bleeding (UGIB). A total of 239 consecutive patients who had
      undergone endoscopy due to nonvariceal UGIB were prospectively investigated on
      the basis of five scoring systems (Forrest classification, Rockall scoring
      system, Cedars-Sinai Medical Centre Predict Index, Blatchford scoring system, and
      Baylor college scoring system). Thirty-five patients (14.6%) experienced
      rebleeding and 20 patients (8.4%) died. Comparison of the high-risk categories of
      the four predictive systems showed that the Forrest classification was superior
      to the others in predicting rebleeding and death. The Cedars-Sinai Medical Centre
      Predict Index and the Rockall scoring system showed high positive predictive
      values for predicting rebleeding and death, respectively. We concluded that the
      Forrest classification was the most useful scoring system for the prediction of
      rebleeding and death in patients with nonvariceal UGIB.

PMID- 19104935
TI  - Protection of regenerating liver after partial hepatectomy from carbon
      tetrachloride hepatotoxicity in rats: roles of mitochondrial uncoupling protein 2
      and ATP stores.
AB  - Uncoupling protein 2 (UCP(2)), an inner mitochondrial membrane protein, can limit
      the generation of reactive oxygen species (ROS) and protect cells from injuries
      mediated by oxidative stress. We investigated the effect of upregulation of
      UCP(2) in the regenerating liver 96 h after 68% partial hepatectomy (PH) on the
      self-protection of regenerating liver against carbon tetrachloride (CCl(4))
      poisoning. Hepatotoxicity was induced in vivo by administering CCl(4) to rats
      that had undergone PH. After CCl(4) poisoning, the regenerating liver appeared to
      have less histological damage and lower serum alanine aminotransferase (ALT)
      levels. Lower malondialdehyde production and higher glutathione contents were
      also observed in the regenerating liver compared with the sham-operated liver
      after CCl(4) poisoning. UCP(2) expression was markedly elevated in the
      regenerating liver, and further increased after CCl(4) intoxication.
      Mitochondrial membrane potential and adenosine triphosphate stores maintained
      higher levels in the regenerating liver than in sham-operated liver after CCl(4)
      intoxication. The results showed that the regenerating liver exhibited a potent
      ability to resist CCl(4) intoxication, and the autoprotection of regenerating
      liver might result from reduction of ROS by UCP(2) and maintenance of higher ATP
      stores.

PMID- 19104933
TI  - The current state of proteomics in GI oncology.
AB  - Proteomics refers to the study of the entire set of proteins in a given cell or
      tissue. With the extensive development of protein separation, mass spectrometry,
      and bioinformatics technologies, clinical proteomics has shown its potential as a
      powerful approach for biomarker discovery, particularly in the area of oncology.
      More than 130 exploratory studies have defined candidate markers in serum,
      gastrointestinal (GI) fluids, or cancer tissue. In this article, we introduce the
      commonly adopted proteomic technologies and describe results of a comprehensive
      review of studies that have applied these technologies to GI oncology, with a
      particular emphasis on developments in the last 3 years. We discuss reasons why
      the more than 130 studies to date have had little discernible clinical impact,
      and we outline steps that may allow proteomics to realize its promise for early
      detection of disease, monitoring of disease recurrence, and identification of
      targets for individualized therapy.

PMID- 19104936
TI  - Cytotoxic T-lymphocyte-associated antigen 4 antibody-induced colitis and its
      management with infliximab.
AB  - Anti-CTLA-4 antibodies are human monoclonal antibodies previously studied in the
      treatment of metastatic melanoma (MM). CTLA-4 is an inhibitory receptor on
      cytotoxic T cells, blockade of which will activate T cells allowing them to
      attack malignant cells. Normal host cells may also be affected, and immune
      mediated enterocolitis can occur. This is a prospective observational study on
      the use of corticosteroids and infliximab in the treatment of patients with
      immune-mediated colitis secondary to anti-CTLA-4 antibody treatment of MM. Five
      patients presented with colitis after medication administration. Patients were
      treated with high-dose corticosteroids for 1 week, but diarrhea did not
      completely abate in any of them. They were then treated successfully with
      infliximab. One patient had recurrence of symptoms and responded to repeat
      treatment with infliximab. Patients who develop immune-mediated colitis after
      administration of anti-CTLA-4 antibodies have previously been reported to respond
      to corticosteroids, but in our study, all required treatment with infliximab.

PMID- 19104937
TI  - Home telemanagement for patients with ulcerative colitis (UC HAT).
AB  - Effective therapies exist to treat ulcerative colitis (UC); nonadherence,
      inadequate monitoring, and side-effects result in suboptimal outcomes. Novel
      methods for monitoring are needed. Our objectives were to assess acceptance of
      home automated telemanagement in ulcerative colitis (UC HAT). The UC HAT system
      consists of a laptop connected to a scale, a decision support server, and a web
      based clinician portal. The UC HAT system facilitates self-care in UC patients by
      monitoring patient symptoms, side-effects, and adherence, and helping patients in
      following their individualized treatment plans. Ten adult patients with UC were
      trained to use UC HAT. Attitudinal surveys and qualitative interviews were
      performed. The results showed that all patients reported that use of the computer
      was not complicated. 90% reported that the symptom diary and side-effect
      questions were not difficult. All patients reported that the training was
      adequate and 70% reported that testing took little time. Seventy percent would
      feel safer using the system, and 90% would agree to use UC HAT in the future.
      Patients felt UC HAT would keep the patient and provider up to date on changes in
      symptoms. Self-testing appeared to make patients accountable for managing the
      disease. It was discussed that improved monitoring is needed for UC. Patients
      with UC can be easily trained to use HAT, and patient acceptance of the UC HAT
      system is high. Home automated telemanagement has potential to improve clinical
      outcomes and patient satisfaction in UC.

PMID- 19104939
TI  - Association of MicroRNA-223 expression with hepatic ischemia/reperfusion injury
      in mice.
AB  - MicroRNAs are a group of small non-coding RNAs with modulator activity of gene
      expression. Recent studies have uncovered a profound role of microRNAs in liver
      diseases. This study aimed to investigate a potential relationship between
      microRNA-223 (miR-223) expression and hepatic ischemia/reperfusion injury in
      mice. Quantitative RT-PCR analysis showed that miR-223 expression levels were
      greatly up-regulated in the livers after 75 min ischemia followed by 120 min
      reperfusion when compared to sham controls (2.59 +/- 0.23 vs. 0.83 +/- 0.15; P <
      0.01). Correlation analysis also revealed that hepatic miR-223 expression level
      was significantly positively correlated with serum markers of ischemic injury. By
      prediction assay of miRNA targets mRNA, acyl-CoA synthetase long-chain family
      member 3, ephrin A1, and ras homolog gene family member B were predicted to be
      downstream targets of miR-223. Thus, we conclude that hepatic
      ischemia/reperfusion injury might be another form of liver disease that is
      associated with alteration in miR-223 expression.

PMID- 19104938
TI  - Chemical colitis due to glutaraldehyde: case series and review of the literature.
AB  - Chemical colitis can occur as a result of accidental contamination of endoscopes
      or by intentional/accidental administration of enemas containing various
      chemicals.We present three cases of glutaraldehyde induced colitis and review the
      cases in the literature. Glutaraldehyde induced colitis presents clinically with
      severe abdominal pain, bloody and mucoid diarrhea, rectal bleeding, and tenesmus
      48-72 h after colonoscopy. Endoscopic findings are nonspecific and mimic ischemic
      colitis, inflammatory bowel disease, and infectious colitis. The timing of
      symptoms and the knowledge that glutaraldehyde is a chemical irritant to colonic
      mucosa is important for the diagnosis. The treatment is mainly supportive but
      sometimes necessitates mesalamine, prednisolone, or metronidazole and the
      resolution is rapid. In endoscopy units, strict adherence to published
      disinfection protocols is very important and the cleaning, rinsing and drying
      protocols also deserve the same attention.

PMID- 19104940
TI  - Evaluation of chondrocyte growth in the highly porous scaffolds made by fused
      deposition manufacturing (FDM) filled with type II collagen.
AB  - Highly porous poly(D,L-lactide-co-glycolide) (PLGA) scaffolds for cartilage
      tissue engineering were fabricated in this study using the fused deposition
      manufacturing (FDM) process and were further modified by type II collagen. The
      average molecular weight of PLGA decreased to about 60% of the original value
      after the melt-extrusion process. Type II collagen exhibited sponge-like
      structure and filled the macroporous FDM scaffolds. An increase of the fiber
      spacing resulted in an increase of the porosity. The storage modulus of FDM
      scaffolds with a large fiber spacing was comparable to that of the native porcine
      articular cartilage. Although the FDM hybrid scaffolds were swollen in various
      extents after 28 days of in vitro culture, the seeded chondrocytes were well
      distributed in the interior of the scaffolds with a large fiber spacing and
      neocartilage was formed around the scaffolds. The study also suggested that a low
      processing temperature may be required to produce PLGA precision scaffolds using
      FDM.

PMID- 19104941
TI  - Selective trapping of live and dead mammalian cells using insulator-based
      dielectrophoresis within open-top microstructures.
AB  - The manipulation of biological cells is essential to many biomedical
      applications. Insulator-based dielectrophoresis (iDEP) trapping consists of
      insulating structures which squeeze the electric field in a conductive solution
      to create a non-uniform electric field. The iDEP trapping microchip with the open
      top microstructures was designed and fabricated in this work. For retaining the
      merit of microfabrication, the microelectrodes were deposited on the substrate to
      reduce the voltage required, due to the shortened spacing between them. The
      dielectrophoretic responses of both live and dead HeLa cells under different
      frequencies (100 Hz, 1 kHz and 1 MHz) have been investigated herein. The live
      cells exhibited negative dielectrophoresis at low frequencies of 100 Hz and 1
      kHz, but a positive dielectrophoretic response with the frequency at 1 MHz. As
      for dead cells, positive dielectrophoretic responses were shown at all the
      frequencies applied. Therefore, selective trapping of dead HeLa cells from live
      cells was achieved experimentally at the frequency of 1 kHz. The open-top
      microstructures are suitable for trapping cells or biological samples, and easily
      proceeding to further treatment for cells, such as culturing or contact
      detection. The intensity of the emitted light during fluorescent detection will
      not suffer interference by a cover, as it does not exist herein.

PMID- 19104942
TI  - Unusual clinical presentations of giant prolactinomas.
AB  - Giant prolactinomas are rare pituitary tumors which have scarcely been reported
      in the literature. We describe three men with unusual presenting features of
      prolactin-secreting giant pituitary adenomas: prolonged and increasingly
      disturbing intolerance to light and noise; strange behavior and mood
      disturbances; and rhinorrhea followed by a finding of cerebrospinal fluid
      leakage. Treatment with dopamine agonist alleviated all symptoms, with
      concomitant suppression of plasma prolactin levels and a significant reduction in
      tumor mass. These cases emphasize the importance of considering unusual symptoms
      in the differential diagnosis of giant prolactinomas and the effectiveness of
      medical treatment.

PMID- 19104943
TI  - Use of city-archival data to inform dimensional structure of neighborhoods.
AB  - A growing body of research has explored the impact of neighborhood residence on
      child and adolescent health and well-being. Most previous research has used the
      US Census variables as the measures of neighborhood ecology, although informative
      census data are not designed to represent the sociological and structural
      features that characterize neighborhoods. Alternatively, this study explored the
      use of large-city administrative data and geographical information systems to
      develop more uniquely informative empirical dimensions of neighborhood context.
      Exploratory and confirmatory structural analyses of geographically referenced
      administrative data aggregated to the census-block group identified three latent
      dimensions: social stress, structural decline, and neighborhood crime. Resultant
      dimensions were compared through canonical regression to those derived from US
      Census data. The relative explanatory capacity of the city-archival and census
      dimensions was assessed through multilevel linear modeling to predict
      standardized reading and mathematics achievement of 31,742 fifth- and 28,922
      eight-grade children. Results indicated that the city-archival dimensions
      uniquely augmented predictions, and the combination of city and census dimensions
      explained significantly more neighborhood effects on achievement than did either
      source of neighborhood information independently.

PMID- 19104944
TI  - Accessing specialty behavioral health treatment in private health plans.
AB  - Connecting people to mental health and substance abuse services is critical,
      given the extent of unmet need. The way health plans structure access to care can
      play a role. This study examined treatment entry procedures for specialty
      behavioral health care in private health plans and their relationship with
      behavioral health contracting arrangements, focusing primarily on initial entry
      into outpatient treatment. The data source was a nationally representative health
      plan survey on behavioral health services in 2003 (N = 368 plans with 767 managed
      care products; 83% response rate). Most health plan products initially authorized
      six or more outpatient visits if authorization was required, did not routinely
      conduct telephonic clinical assessment, had standards for timely access, and
      monitored wait time. Products with carve-outs differed on several treatment entry
      dimensions. Findings suggest that health plans focus on timely access and
      typically do not heavily manage initial entry into outpatient treatment.

PMID- 19104946
TI  - This special issue of JCPMS is dedicated to Nathan Warren Perry, Jr. July 6, 1932
      December 1, 2007.

PMID- 19104947
TI  - Psychologists in academic health centers: traditions and innovations in
      education, science, and practice.
AB  - Psychologists, interns, and postdoctoral fellows convened in Minneapolis May 3-5,
      2007 for the 3rd National Conference of the Association of Psychologists in
      Academic Health Centers (APAHC): "Psychologists in Academic Health Centers:
      Traditions and Innovations in Education, Science, and Practice." This paper
      reviews the development and organization of the conference, which built upon the
      two previous conferences of the Association of Medical School Psychologists. The
      articles in this special issue are based on a selected number of the 32
      conference presentations, covering a range of timely topics that reflect the
      conference theme. Participants' positive perceptions and satisfaction with the
      conference reveal the value of such conferences focused on the activities,
      interests, opportunities, and challenges of psychologists who work in academic
      health centers (AHCs) and teaching hospitals. Moreover, the content and success
      of the conference underscores the importance of APAHC as an organization serving
      the needs and promoting the interests of psychologists affiliated with AHCs.

PMID- 19104945
TI  - PTD-mediated loading of tumor-seeking lymphocytes with prodrug-activating
      enzymes.
AB  - Using the approach of peptide transduction domain (PTD)-mediated loading of
      interleukin-2(IL-2)-activated natural killer (A-NK) cells, tumor-seeking
      lymphocytes, with prodrug-activating enzymes, we primarily aim to generate a
      cytotoxic drug selectively within tumors and minimize damage to normal tissues. A
      NK cells are able to accumulate selectively at tumor sites. While these cells by
      themselves possess significant antitumor effect in vivo, we suggest that they can
      also serve as Trojan horses, by bringing anticancer agents, such as prodrug
      activating enzymes, selectively to tumors. We have successfully demonstrated in a
      mouse model that A-NK cells can be rapidly loaded with prodrug-activating
      enzymes, such as alkaline phosphatase (AP) and beta-galactosidase (beta-gal), in
      vitro using enzyme-conjugated peptide PTD5. Upon adoptive transfer into lung
      tumor-bearing animals, the loaded A-NK cells are able to bring their cargo of the
      prodrug-activating enzymes selectively to pulmonary metastases. The targeting of
      the AP to the tumor tissues is highly specific, since more than a fivefold higher
      concentration of AP was found in the tumor tissues compared to the surrounding
      normal lung tissue at 24 h after injection. The approach of transporting prodrug
      activating enzymes selectively into tumors clearly shows potential for future
      targeted chemotherapy. Ongoing studies in our laboratory are evaluating the
      antitumor efficacy of cellular-dependent enzyme prodrug therapy.

PMID- 19104948
TI  - The forgotten faculty: challenges for Ph.D.s in clinical medical school
      departments.
AB  - The data and discussion contained in this invited paper are based on the opening
      plenary by the first author whose paper titled "The Status of Ph.D.s in US
      Medical Schools" was presented at the 3rd national conference of the Association
      of Psychologists in Academic Health Centers, Minneapolis, MN, May 2007. The
      significant growth of the number of Ph.D.s in clinical departments is described,
      as is their distribution. The roles they play; the barriers they face in terms of
      leadership opportunities, promotion and tenure; and the concerns they voice that
      are specific to this population are also discussed. Salary differentials between
      Ph.D.s on main and medical school campuses are provided. Recommendations for
      future investigation of disparate treatment and for faculty development
      opportunities specifically aimed at this group are found at the conclusion of the
      paper.

PMID- 19104949
TI  - Changing educational needs of psychologists: do we need more medical knowledge,
      basic science and more psychological science?
AB  - Psychologists of the 21st century must be highly skilled and versatile to
      function effectively in academic health centers (AHCs). Thus, the current paper
      focuses on the training psychologists receive to prepare them for their diverse
      roles in AHCs. The paper is framed around the question: Do we need more medical
      knowledge, basic science and more psychological science? posed to the author by
      the conference organizers of the 3rd National Association of Psychologists in
      Academic Health Centers (APAHC) Conference and is based on the perspective of the
      author.

PMID- 19104950
TI  - Competencies for psychologists in Academic Health Centers (AHCs).
AB  - This paper begins by providing the landscape that undergirds the competency-based
      movement within professional psychology education, training, credentialing, and
      performance appraisal. Attention is then paid to the relevance of this culture
      shift for psychologists working as practitioners, educators, researchers, and
      administrators in AHCs. In this regard, there is an articulation of the essential
      subcomponents of each of the core foundational and functional competency domains
      that are salient for AHC psychologists. Implications of the competency-based
      movement for professional psychologists in AHCs are offered.

PMID- 19104951
TI  - ACGME core competencies: helpful information for psychologists.
AB  - The mission of the Accreditation Council for Graduate Medical Education (ACGME)
      is to improve graduate medical education in order to ultimately improve the
      quality of healthcare. To meet this mission the ACGME has firmly established a
      competency based focus for resident education. The current manuscript describes
      the six general ACGME competencies of Patient Care, Medical Knowledge, Practice
      based Learning and Improvement, Interpersonal and Communication Skills,
      Professionalism and Systems-based Practice. Then, a brief description of efforts
      by the institution of the authors to create best practice models for competency
      based curriculums and outcomes is provided. Specific focus is on strategies used
      within the psychiatry residency and ways a Graduate Psychology Education grant
      fostered interdisciplinary training between psychology and family medicine that
      enhanced the development of competencies for both disciplines. The paper also
      comments on the training experiences and attitudes that can prepare psychologists
      to assist physician colleagues in meeting competencies.

PMID- 19104952
TI  - Advancing psychology as a bio-behavioral science.
AB  - Concerns for the integrity of psychology as an independent discipline have caused
      some psychologists to object to introducing any knowledge from the biological
      sciences into the training of psychologists. However, calls for the greater
      incorporation of the behavioral sciences in medical education, increased
      attention to research on the mechanisms of bio-behavioral interaction, and
      initiatives in translational medical research and clinical care, have prompted
      increased interest in interdisciplinary research, health care, and teaching.
      These changes, in turn, are resulting in a re-conceptualization of the structure
      of academic medicine with increasing emphasis upon multidisciplinary knowledge
      and interdisciplinary collaboration, and less emphasis upon disciplinary
      insularity and competitiveness. If clinical health psychology is to play a role
      in this evolving concept of academic health care, it must adequately prepare its
      trainees to function in interdisciplinary academic health care settings. This
      will require not only expertise in the role of behavioral factors relevant to
      medical disorders, but also some basic familiarity with the biological processes
      to which those behavioral factors relate. With the evolution of its fund of
      knowledge, clinical health psychology has the potential to utilize its science to
      discover, describe, interpret, teach and clinically apply knowledge of the
      mechanisms of interaction between biological functions and behavioral, learning,
      cognitive, socio-cultural and environmental processes. By failing to seize this
      initiative, clinical health psychology risks becoming irrelevant to the evolving
      model of medical research, education and health care.

PMID- 19104953
TI  - An international perspective on behavioral science education in medical schools.
AB  - The behavioral sciences are taught in medical curricula around the world. In the
      current paper psychologists teaching in medical schools in Australia, Mexico,
      Saudi Arabia, Thailand, the United Kingdom and the United States share their
      experience and reflections. Whilst direct comparisons between countries are not
      made, the themes that are evident within and between accounts are instructive. As
      behavioral scientists around the globe are struggling to maintain a presence in
      medical education many of the reasons behind this are shared, regardless of the
      country. Challenges discussed include those related to the impact of unrealized
      potential contributions of psychologists as health care professionals, teaching
      of behavioral sciences by other professions, domination of the biomedical model
      without a corresponding recognition of psychology as science, and modern medical
      pedagogies such as problem-based learning, which favor biomedicine. Systemic and
      political barriers over which we as a discipline may have little control are also
      highlighted.

PMID- 19104954
TI  - Recommendations for research success: one investigator's perspective.
AB  - This article is a personal reflection by an investigator with over 25 years of
      funding from the National Institutes of Health (NIH). The article: (1) highlights
      research opportunities for psychologists at the NIH outside of the traditional
      mental health arena; (2) provides specific recommendations to individual
      investigators to enhance their likelihood of obtaining NIH funding; (3) specifies
      needed changes in psychology's research education and training programs to
      prepare the next generation of psychologists for research success; and (4) asks
      the Association of Psychologists in Academic Health Centers to play a lead role
      in both research training and advocacy.

PMID- 19104955
TI  - The NIH Roadmap: are psychologists in or out?
AB  - Psychologists often express concerns about the inclusion of psychology in the
      National Institutes of Health (NIH) Roadmap initiative. Most Roadmap themes focus
      on biomedical research, forming the basis for psychologists' concerns. Although
      most Roadmap funding goes toward biomedical research, social and behavioral
      scientists do win support. It is reasonable to ask, however, why the Roadmap is
      focused so exclusively on medical research. One explanation is that medical
      interventions are seen as the natural translation of basic biomedical research,
      whereas psychological interventions are not perceived as following from basic
      behavioral research. Psychologists working in academic health centers represent
      the best opportunity for creating such linkages, and therefore the best potential
      bridge for psychology connecting to the NIH Roadmap.

PMID- 19104956
TI  - The difficulty of making psychology research and clinical practice relevant to
      medicine: experiences and observations.
AB  - Psychology and medicine research and practice have demonstrated substantial and
      unique bodies of knowledge designed to both improve patient care and respond to
      contemporary health care needs for use of evidence and cost consciousness. At
      their full potential they represent a significant paradigm shift in healthcare.
      Despite impressive successes, it is clear that we are just on the cusp of such a
      change. These findings have had limited impact and penetration into medical
      practice, particularly outside of academic medicine and large, organized systems
      of health care, and there are multiple examples of such limitations in various
      arenas of health care. There also appear to be common themes to such examples
      which provide us opportunities to consider how psychologists might move things
      ahead. They also suggest how our unique position in academic medicine can both
      limit our impact and provide ways of creating continued shifts in the healthcare
      paradigm.

PMID- 19104957
TI  - Integrating mental health and primary care services in the Department of Veterans
      Affairs health care system.
AB  - Integrating mental health care in the primary care setting has been identified in
      the literature as a model for increasing access to mental health services and has
      been associated with enhanced clinical and functional patient outcomes and higher
      patient satisfaction. The Department of Veterans Affairs (VA), which operates the
      nation's largest integrated health care system, has taken a leadership role in
      creating a health care system in which mental health care is provided in the
      primary care setting. This article examines VA's efforts and progress to date in
      implementing evidence-based models of integrated mental health services
      nationally in community based outpatient clinics, home based primary care, and
      outpatient primary clinics at medical facilities. Psychology plays an important
      role in this progress, as part of an overall interdisciplinary effort, in which
      all professions are crucially important and work together to promote the overall
      well-being of patients.

PMID- 19104958
TI  - Psychologists in academic health centers: reflections on traditions and
      innovations in education, science, and practice.
AB  - In 2007, the Association of Psychologists in Academic Health Centers (APAHC),
      formerly known as Association of Medical School Psychologists (AMSP), held its
      first national conference since 1997. At the latter conference, the author of
      this article [Sheridan (1999) Journal of Clinical Psychology in Medical Settings,
      6, 211-218] was asked to present some of the issues that would be important to
      health care psychologists in the next decade. These issues included the role of
      psychology in academic health centers, interventions psychologists offer,
      reimbursements for such treatments, education and training models, and research.
      This article examines those observations, offers new data, and explores the
      current challenges and opportunities for psychologists in academic health
      centers. The presentation also addresses aspirations of psychologists as well as
      resistances within the profession.

PMID- 19104959
TI  - Times are changing in Academic Health Centers, or maybe not: our next national
      conference.

PMID- 19104960
TI  - Our case debut: a case presentation from the Association of Psychologists in
      Academic Health Centers.

PMID- 19104962
TI  - Perfectionism and depression among low-income chronically ill African American
      and White adolescents and their maternal parent.
AB  - Most research on perfectionism is based on convenience samples of university
      students or clinically distressed samples, and therefore relatively less is known
      about the development and implications of perfectionism for other groups. In this
      study, we examined perfectionism and depression in low-income African American (n
      = 39) and White (n = 55) adolescents with chronic illnesses (most with diabetes,
      asthma, and/or hypertension) and their primary parents. We specifically examined
      the association between parent and child perfectionism, and the link between
      perfectionism and depression in both groups. The African American adolescents
      reported significantly more maladaptive perfectionism than did the White
      adolescents, and the African American parents reported significantly higher
      scores on depression than did the White parents. Correlations and regression
      analyses revealed similarities and differences in perfectionism-depression
      associations that might be explained in light of cultural differences and the
      unique physical and emotional challenges faced by youth with chronic illnesses.

PMID- 19104963
TI  - Catastrophizing as a cognitive vulnerability factor related to depression in
      workers' compensation patients with chronic musculoskeletal pain.
AB  - The purpose of this study was to examine the role of catastrophizing as a
      mediator and moderator between life stress and depression in a sample of workers'
      compensation patients with chronic musculoskeletal pain. Pain intensity, life
      stress (especially work and financial stress), and catastrophizing contributed
      significantly to depression. Catastrophizing was found to be partially mediating
      the relationship between life stress and depression and a moderator between
      social stress and depression. The results supported the role of catastrophizing
      as a cognitive vulnerability-stress factor related to depression in chronic pain
      patients. Screening for life stress and intervening early to prevent
      catastrophizing from occurring in the workers' compensation rehabilitation
      process may reduce psychosocial distress and enhance the overall effectiveness of
      rehabilitation programming for workers' compensation patients with chronic pain.

PMID- 19104964
TI  - Variables related to posttraumatic growth in Turkish rheumatoid arthritis
      patients.
AB  - Rheumatoid arthritis (RA) is a chronic, deteriorative disease, which can cause
      great psychological distress. Although RA has negative psychological
      consequences, it may also lead to positive changes, which has been given
      relatively little attention in the research literature. The Posttraumatic Growth
      Inventory (PTGI) has been used to evaluate growth in survivor's thinking, feeling
      and/or behavior following the experiencing of traumatic or severely adverse life
      events. The purpose of the current study was to examine the domains of the PTGI
      and to identify variables related to Posttraumatic Growth (PTG) in 117 RA
      patients from Turkey, a secular, Islamic, non-western developing country. Results
      showed that the PTGI has three domains: relationship with others; philosophy of
      life; and self-perception. Regression analyses showed that problem-focused coping
      had significant contributions to the total PTG levels and PTGI domains of
      relationship with others and self-perception. Perceived social support appeared
      as a significant associate for the total PTG levels and for all three domains. In
      addition, age and perceived disease severity were found to be significantly
      related to some domains of PTG. Clinicians, aiming to increase positive
      experience of RA patients, may need to focus on and facilitate perceived social
      support and problem-focused coping to facilitate growth experiences.

PMID- 19104965
TI  - Socioeconomic differences in psychosocial factors contributing to coronary heart
      disease: a review.
AB  - Psychosocial factors have been shown to play an important role in the aetiology
      of coronary heart disease (CHD). A strong association between CHD and
      socioeconomic status (lower-level education, poor financial situation) has also
      been well established. Socioeconomic differences may thus also have an effect on
      psychosocial risk factors associated with CHD, and socioeconomic disadvantage may
      negatively affect the later prognosis and quality of life of cardiac patients.
      The aim of this study was to review the available evidence on socioeconomic
      differences in psychosocial factors which specifically contribute to CHD. A
      computer-aided search of the Medline and PsycINFO databases resulted in 301
      articles in English published between 1994 and 2007. A comprehensive screening
      process identified 12 empirical studies which described the socioeconomic
      differences in CHD risk factors. A review of these studies showed that
      socioeconomic status (educational grade, occupation or income) was adversely
      associated with psychosocial factors linked to CHD. This association was evident
      in the case of hostility and depression. Available studies also showed a similar
      trend with respect to social support, perception of health and lack of optimism.
      Less consistent were the results related to anger and perceived stress levels.
      Socioeconomic disadvantage seems to be an important element influencing the
      psychosocial factors related to CHD, thus, a more comprehensive clarification of
      associations between these factors might be useful. More studies are needed,
      focused not only on well-known risk factors such as depression and hostility, but
      also on some lesser known psychosocial factors such as Type D and vital
      exhaustion and their role in CHD.

PMID- 19104966
TI  - Obesity in America: implications for clinical and health psychologists.
AB  - The number of individuals classified as overweight and obese is increasing at
      alarming rates and these conditions are associated with numerous psychological
      and physiological health problems. Within this epidemic, there is an increasing
      need and demand for psychologists and other mental health professionals to
      participate in the care of patients with obesity, both in assessment and
      treatment domains. The current paper provides a review of the status of the
      obesity epidemic, including psychological comorbidities and treatment approaches.
      Throughout this review, we highlight and discuss the important roles and impact
      psychologists can have. These roles include serving as members of
      multidisciplinary obesity treatment programs, conducting assessments for
      bariatric surgery, and treating related psychiatric disorders, such as depression
      and disordered eating. Other considerations, such as weight gain associated with
      psychiatric medications, and directions for future involvement of psychologists
      in addressing the obesity epidemic are also discussed.

PMID- 19104967
TI  - Psychometric properties and cut-off scores of the Beck Depression Inventory-II in
      Turkish adolescents.
AB  - The current study examined the psychometric properties and cut-off scores of the
      Beck Depression Inventory II in Turkish adolescents. A total of 503 non-clinical
      and 166 clinical adolescents participated in the study. Test-retest (r = .89) and
      internal consistency (alpha = .90) reliabilities, convergent validity (r = .81)
      and discriminant validities (r = .39, r = .49 and r = .42) were satisfactory.
      Exploratory factor analyses yielded two factors. The cut-off score for mild
      depression in Turkish adolescents was lower than that reported previously for
      adults. The findings are discussed in relation to those of previous studies
      conducted in other countries.

PMID- 19104968
TI  - Childhood healthcare experience, healthcare attitudes, and optimism as predictors
      of adolescents' healthcare behavior.
AB  - Late adolescence and early adulthood is a time when people establish many of
      their life-style behaviors. Thus, in order to promote optimal health, it is
      important to identify factors predictive of young adults' healthcare behavior.
      This study evaluated the relationship between measures of childhood healthcare
      experience, healthcare attitudes, and optimism with young adults' healthcare
      behavior in a sample of college students (n = 100). Results suggested that prior
      healthcare experience, attitudes about healthcare, and optimism are associated
      with current healthcare behavior. In addition, the relation between childhood
      healthcare experience and current healthcare behavior was moderated by optimism,
      such that those who reported both more negative childhood healthcare experiences
      and low levels of optimism reported the least adaptive healthcare behaviors and
      those who reported the most positive childhood healthcare experience and the
      highest levels of optimism reported the most adaptive healthcare behavior.

PMID- 19104969
TI  - Variations in psychological profile among children with recurrent abdominal pain.
AB  - This study was designed to determine whether distinct subgroups of children with
      recurrent abdominal pain (RAP) could be identified based on patterns of
      psychological functioning. Two hundred and eighty-three children (ages 8-17
      years), and a primary caretaker, completed the Behavior Assessment System for
      Children (BASC) during the initial evaluation of RAP at a pediatric
      gastroenterology clinic. Cluster analysis of BASC scores supported a 3-cluster
      solution, with fair agreement observed between parents and children on cluster
      assignment. Approximately half of the sample identified no significant
      psychological problems. A small percentage (13%) evidenced intense and broad
      based psychological problems, while the remainder (35-45%) indicated relative
      elevations in anxiety only. Cluster membership did not vary systematically by
      age, gender, race, or functional gastrointestinal disorder diagnosis. Distinct
      psychological profiles appear to exist for children with RAP. Targeting
      treatments to these profiles may improve the effectiveness and efficiency with
      which health professionals address pediatric abdominal pain.

PMID- 19104970
TI  - Fear of hypoglycemia in parents of young children with type 1 diabetes mellitus.
AB  - The current study examined fear of hypoglycemia in 81 mothers and 64 fathers of
      young children with type 1 diabetes (T1DM) using the Hypoglycemia Fear Survey
      Parents of Young Children (HFS-P-YC possible range = 26-130). Mothers and fathers
      completed the HFS-P-YC at enrollment and mothers completed it 2 weeks later.
      Families recorded daily blood glucose on a standardized meter for 2 weeks.
      Mothers' mean total HFS-P-YC score was 75.0 (SD = 17.2) and fathers' mean score
      was 66.5 (SD = 18.0). Mothers reported greater HFS-P-YC total and behavior
      subscale scores than fathers. Mothers' HFS-P-YC scores were comparable to
      published HFS scores for mothers of preadolescents with T1DM and higher than
      adult patients with T1DM. The HFS-P-YC had good internal consistency and test
      retest reliability in this sample. These findings suggest parents of young
      children with T1DM report a high level of fear of hypoglycemia. Additionally, the
      HFS-P-YC appears to be a reliable measure in this population.

PMID- 19104972
TI  - Innovative methods for making behavioral science relevant to medical education.
AB  - Thousands of psychologists teach in U.S. medical schools, and these psychologists
      are responsible for ensuring that the medical students they train are aware of
      the ways in which research findings from the behavioral and social sciences can
      enhance the practice of medicine. In addition, it is imperative that physicians
      appreciate the limits of their own ability to treat psychological and psychiatric
      problems and know when to refer to mental health professionals. This brief
      article is based on a talk given by the author at the 2007 American Psychological
      Association (APA) convention after receiving the Association of Psychologists in
      Academic Health Centers (APAHC) Ivan Mensh Award for Distinguished Achievement in
      Teaching. The paper draws on the personal experiences of the author after three
      decades spent teaching behavioral science to medical students, and it introduces
      readers to the reasoning behind many of the decisions made in planning and
      developing each of the author's four editions of the medical school text Behavior
      and Medicine.

PMID- 19104973
TI  - Treating depressed children with antidepressants: more harm than benefit?
AB  - Since the FDA held hearings in February 2004 on the safety of antidepressants in
      children, there has been a great deal of controversy regarding the use of
      antidepressants in children, culminating in the well publicized black box
      warnings about increased risk of suicidal behavior in children and young adults
      (up to age 25) caused by these medications. Using questions that a parent might
      ask, the current article attempts to summarize the efficacy and safety data on
      the use of antidepressants in children so that psychologists, with or without
      prescription privileges, may be able to inform parents of young patients about
      the science behind this treatment. This article is based on a presentation at the
      2007 American Psychological Association conference by the author in acceptance of
      the 2006 APAHC Bud Orgel Award for Distinguished Achievement in Research. Much of
      the information described in this article is drawn from the recent APA Report of
      the Working Group on Psychoactive Medications for Children and Adolescents.
      (Brown et al. 2006; available at www.apa.org/pi/cyf/childmeds.pdf ) culminating
      in a book by the same authors (Brown et al., Childhood mental health disorders:
      Evidence base and contextual factors for psychosocial, psychopharmacological, and
      combined interventions 2007).

PMID- 19104974
TI  - The MMPI-2: a contemporary normative study of midwestern family medicine
      outpatients.
AB  - For more than 60 years it has been known that profiles from the Minnesota
      Multiphasic Personality Inventory (MMPI), obtained from medical patients, are
      elevated when scores are plotted using general population norms. These elevations
      have been most apparent on the neurotic triad (NTd), the first 3 clinical scales
      on the MMPI profile. More than 45 years have passed since a nonreferred,
      normative sample of MMPIs was established from 50,000 consecutive medical
      outpatients. We present comparable but contemporary normative data for the
      revised MMPI (MMPI-2) based on a nonreferred sample of 1,243 family medicine
      outpatients (590 women; 653 men). As true for the original MMPI, contemporary
      medical outpatients have profiles that are significantly different, clinically
      and statistically, from the general population norms for the MMPI-2. This is
      particularly evident in elevations on the NTd. New normative tables of uniform
      medical T (UMT) scores were developed following the procedures used to create the
      uniform T scores for the MMPI-2. Measures of internal consistency are reported;
      test-retest reliability was established over a mean of 3.7 weeks, and results
      characterizing the stability of the validity and clinical scales are presented.

PMID- 19104975
TI  - Implementation of effective treatments of preschool behavior problems in a clinic
      setting.
AB  - Epidemiological data indicate that nearly 20% of preschool aged children have
      significant behavioral problems. Parents typically consult their child's primary
      care provider, who frequently refers to child psychologists for treatment
      regarding these difficulties. Psychologists skilled in providing effective
      services for young children are in short supply, limiting accessibility, and
      parents often are reluctant to follow up with a mental health specialist,
      suggesting low acceptability. The Behavior Consultation Clinic is a structured
      clinic for preschool children designed to address these issues of effectiveness,
      accessibility and acceptability. A retrospective review of 550 patients seen over
      a 5-year period found that half were seen for one therapy session. Review of the
      remaining patients found that slightly more than half showed improvement (32%
      successful discharge with improvement, 24% premature discharge with improvement)
      with a typical range of two to seven half-hour sessions, about a quarter did not
      improve, and the remaining patients were referred to a higher level of service.
      These data indicate that a structured, brief clinic that focuses on the needs of
      preschool children utilizing evidence-based approaches can be effective,
      acceptable, and accessible. The Behavior Consultation Clinic also serves as a
      training clinic for psychology interns and pediatric medical residents.

PMID- 19104976
TI  - Repeat HIV testing and HIV transmission risk behaviors among sexually transmitted
      infection clinic patients.
AB  - HIV testing and counseling expends considerable HIV prevention resources and
      offers great opportunities for HIV risk reduction. Individuals who are at risk
      for HIV and have not been HIV tested are the focus of current targeted testing
      campaigns and yet persons who are repeatedly tested for HIV often continue
      engaging in high-risk practices. This study examined HIV testing, risk behaviors,
      and other medical diagnostic testing practices of men (N = 231) and women (N =
      86) attending an inner-city sexually transmitted infections (STI) clinic. Results
      showed that 75 (23%) participants had not yet been tested for HIV, 45 (14%) had
      been tested once, and 197 (63%) had been tested two or more times. Patients that
      had not been tested and those who were repeatedly tested were similar in their
      risk behaviors; both demonstrated significantly greater risks for HIV than
      persons tested just once, although repeat testers were more likely to have had a
      past STI. HIV testing history was minimally associated with other medical testing
      and health protective practices, such as testicular self-examination,
      mammography, and having had PAP tests. Results support targeting high-risk
      untested persons for HIV testing and suggest an urgent need for interventions to
      reduce risk behaviors among STI clinic patients who repeatedly test for HIV.

PMID- 19104977
TI  - Breast cancer in men: a need for psychological intervention.
AB  - Male breast cancer is a serious issue that needs to be addressed more fully by
      the medical and public community. However, due to a lack of awareness and limited
      research on the topic, there is a general absence of knowledge concerning the
      psychological implications of this disease in men as well as a need for greater
      understanding of the medical diagnosis and treatment of male breast carcinoma.
      Similarly, there still remains a considerable gender difference between the
      awareness of female breast cancer and male breast cancer. Although breast cancer
      in men makes up only 1% of all breast cancers reported in the United States, it
      is increasing in incidence. There are approximately 2000 new cases and
      approximately 450 deaths due to male breast cancer each year. Breast cancer
      diagnosis and treatment in men is very similar to that described in women;
      however, it has been shown that men are being diagnosed at a later stage of the
      disease than women.

PMID- 19104978
TI  - Exercise and depression: a review of reviews.
AB  - There has been considerable research interest in the effects of exercise upon
      depression outcomes. Recently, health agencies in the United Kingdom (UK) and
      beyond have made several guidance statements on this issue. Therefore, this
      review seeks to provide a synthesis of evidence regarding the effectiveness of
      exercise in the management of depression (including postnatal depression) in
      adults. Studies were identified by searching PubMed, Medline, Cochrane Library
      (CENTRAL) and PsychINFO using relevant search terms. The article describes how
      meta-analyses from peer reviewed journals have reported exercise as treatment for
      depression is more effective than no treatment, as effective as traditional
      interventions in some instances, possibly a promising approach to postnatal
      depression and has equivalent adherence rates to medication. However, reviews
      have also raised concerns about the methodological quality of trials, possible
      overestimation of treatment effects and lack of data regarding long term
      benefits. Based on the available evidence it is concluded that while awaiting
      further high quality trial evidence it would seem appropriate for exercise to be
      recommended in combination with other treatments.

PMID- 19104979
TI  - Health-related quality of life in women with eating disorders: association with
      subjective and objective binge eating.
AB  - This study examined health-related quality of life (QOL) and its association with
      different forms of binge eating in 53 women with eating disorders. Participants
      had enrolled in treatment for anorexia nervosa, bulimia nervosa, binge eating
      disorder, or other eating disorders not otherwise specified and completed
      measures of QOL, eating-related psychopathology, and mood disturbance. Eating-
      and mood-related psychopathology, and to a lesser extent, mental-component QOL
      scores, were severely impaired in this sample relative to population norms. QOL
      was significantly and independently predicted by subjective bulimic episodes and
      compensatory behaviors, including food avoidance, laxative abuse, and self
      induced vomiting, accounting for 32% of the variance. Subjective bulimic episodes
      and food avoidance also independently predicted the physical-component QOL,
      accounting for 27% of the variance. These findings suggest that subjective
      bulimic episodes may be independently associated with impairment in QOL and may
      require specific attention as targets of treatment.

PMID- 19104980
TI  - The influence of clinical variables on the psychological adaptation of
      adolescents after solid organ transplantation.
AB  - This study assessed the influence of clinical and socio-demographic variables on
      the psychological adaptation of transplanted adolescents. Twenty-six transplanted
      adolescents and 25 healthy adolescents, aged 13-17, and their parents
      participated in the study. The following domains were measured: social
      competence, emotional/behavioral problems, self-concept, self-esteem and
      subjective well-being. The findings revealed that transplanted boys presented
      significantly less social competence (U = 26,000, p < .05) and more externalizing
      problems (U = 25,000, p < .05), social problems (U = 25,000, p < .05) and
      attention problems (U = 17,500, p < .01) than healthy boys. In contrast,
      transplanted girls displayed significantly more internalizing problems (U =
      47,000, p < .05) and lower physical self-concept (U = 49,500, p < .05) than
      healthy girls. Hierarchical regression analysis showed clinical variables,
      especially waiting-list time, significantly predicted attention problems (beta =
      .364, p < .05) and negative affect (beta = .632, p < .05) in transplanted
      adolescents. Also, male (beta = -0.554, p < .01) and younger (beta = -0.444, p <
      .01) transplanted adolescents were at risk for attention problems. Our data
      suggest the importance of the waiting-list time for transplanted adolescents.
      Efforts to reduce the pretransplant phase would help adolescents achieve better
      psychological adaptation at long-term posttransplant.

PMID- 19104981
TI  - The psychosocial vulnerability model of hostility as a predictor of coronary
      heart disease in low-income African Americans.
AB  - The current study examined social support and stress as mediators of the
      hostility-coronary heart disease (CHD) relationship as suggested by the
      psychosocial vulnerability model in a sample of low-income African Americans.
      Among 95 CHD patients and 30 healthy controls, hostility was negatively
      correlated with social support, but was not related to minor stress. CHD patients
      endorsed higher levels of hostility; however, the relationship between hostility
      and CHD status was diminished once stress and social support were included in the
      model. This study lends partial support for the psychosocial vulnerability model
      of hostility in African Americans, but suggests that the relationship between
      hostility and stress may be impacted by socioeconomic status.

PMID- 19104982
TI  - Perceived history of anaphylaxis and parental overprotection, autonomy, anxiety,
      and depression in food allergic young adults.
AB  - This study examined autonomy, anxiety, depression, and perceptions of parental
      behavior in 86 food allergic young adults and 344 healthy young adults between
      the ages of 18 and 22. Participants completed an online survey measuring self
      reported autonomy, anxiety, depression, and perceptions of parental behavior.
      Results indicated that, as a group, food allergic young adults did not differ
      from healthy peers. However, food allergic young adults who reported having
      experienced an anaphylactic reaction described their disease as more severe,
      reported more worry about their disease, and rated their parents as more
      overprotective than food allergic young adults who reported never having
      experienced anaphylaxis. The experience of anaphylaxis may be a reliable
      indicator of food allergic individuals who are at risk for psychological
      distress.

PMID- 19104983
TI  - Post-traumatic growth after a myocardial infarction: a matter of personality,
      psychological health, or cognitive coping?
AB  - The aim of the present study was to focus on the relative contributions of
      personality, psychological health and cognitive coping to post-traumatic growth
      in patients with recent myocardial infarction (MI). The sample consisted of 139
      patients who had experienced a first-time acute MI between 3 and 12 months before
      data assessment. Multivariate relationships were tested by means of Structural
      Equation Modeling. The results showed that besides the contribution of
      personality and psychological health, a significant amount of variance in growth
      was explained by the cognitive coping strategies people used to handle their MI.
      As cognitive coping strategies are generally assumed to be mechanisms that are
      subject to potential influence and change, this provides us with important
      targets for intervention.

PMID- 19104984
TI  - Age and body satisfaction predict diet adherence in adolescents with Inflammatory
      Bowel Disease.
AB  - The aim of the current study was to determine whether age and body satisfaction
      predict dietary adherence in adolescents with Inflammatory Bowel Disease (IBD),
      and whether older females are less adherent than younger males and females. Forty
      four participants aged 10-21 with IBD were recruited. Participants provided
      informed consent and demographics. Body satisfaction was measured by a
      questionnaire and a task in which participants selected their current and ideal
      body image out of silhouettes depicting bodies ranging from underweight to obese.
      Adherence was measured by marking a 100 mm visual analog scale, the 1-week
      completion of a dietary log, and a questionnaire evaluating coping strategies
      used for overcoming obstacles to dietary adherence. Age was related to dietary
      adherence, with younger children being more likely to adhere. Participants more
      satisfied with their body reported better dietary adherence. Findings remained
      consistent across multiple measures of body satisfaction and adherence.
      Healthcare providers and parents should be informed of these findings in order to
      improve adherence.

PMID- 19104985
TI  - Different associations of health related quality of life with pain, psychological
      distress and coping strategies in patients with irritable bowel syndrome and
      inflammatory bowel disorder.
AB  - The primary aim of this study was to measure psychological distress, pain
      severity, health related quality of life (QOL) and pain coping strategies in
      patients with irritable bowel syndrome (IBS) and ulcerative colitis (UC). A
      second aim was to determine the influence of somatic and psychological variables
      on health related QOL. Eighty-eight IBS and 66 UC patients completed the
      Irritable Bowel Syndrome Quality of Life Questionnaire (IBSQOL), Pain Severity
      Scale of West Haven Yale Multidimensional Pain Inventory (WHYMPY), Symptom
      Checklist-90-R (SCL-90-R) and Coping Strategies Questionnaire (CSQ). T-tests and
      GLM Analysis of Covariance were used for statistical analysis. IBS patients had
      significantly higher levels of psychological distress, pain severity and
      maladaptive pain coping strategies (catastrophization), and lower QOL than UC
      patients. Variance of QOL in IBS was explained for the most part by
      catastrophization (15%), then by psychological distress (8%), and for the less
      part by pain severity (5%). In UC, pain severity explained 21%, psychological
      distress 8%, and catastrophization 3% of the variance of QOL. These results
      suggest there are differences between IBS and UC patients in the role of physical
      and psychological factors in QOL and emphasize the importance of cognitive
      processes in IBS.

PMID- 19104986
TI  - Frequent assessment of negative symptoms does not induce depressed mood.
AB  - Use of real-time data collection is rapidly expanding in the medical sciences and
      questions have been raised as to whether frequent ratings of disease symptoms
      could evoke depressed mood. This study investigated the effect of an intensive
      momentary assessment protocol on depressed mood. Community rheumatology patients
      (N = 105) were recruited to participate in a 30-day momentary assessment protocol
      of pain and fatigue. Patients were randomly signaled and completed approximately
      6 ratings per day and at bedtime. Beck Depression Inventory-II scores were
      obtained prior to and at the completion of the protocol. Thirty-six percent of
      patients were classified initially as mild to severely depressed, and 31% percent
      at the end of the protocol. Depression scores were significantly lower following
      the protocol (p < .001). Whereas 10% of patients shifted into a more depressed
      category at the end of the protocol, 20% shifted into a less depressed category.
      These findings suggest frequent assessment of pain and fatigue may not induce
      depressed mood, and may in some instances be associated with a small reduction in
      depressed mood.

PMID- 19104987
TI  - Optimal scoring of the Multidimensional Pain Inventory in a chronic pain sample.
AB  - The Multidimensional Pain Inventory (MPI) is one of the most commonly used self
      report instruments in pain settings. The MPI can be used to classify patients
      into three clusters or its nine scales can be treated as dimensions in efforts to
      understand patient heterogeneity. Previous research suggests the existence of a
      fourth cluster, whose members have been labeled 'repressors,' that emerges with
      the addition of a defensiveness scale to the MPI. The current paper compared the
      abilities of MPI cluster and dimensional models with and without a measure of
      defensiveness to capture variability in validating variables related to
      personality, psychopathology, physical functioning, and treatment outcome in a
      chronic pain sample. Results suggest that dimensional models consistently
      outperform cluster models in explaining variance in outcome variables, and that
      the addition of a measure of defensiveness increments the validity offered by the
      MPI scales. Implications for the assessment of pain patients are discussed.

PMID- 19104988
TI  - Relationships among religiousness, spirituality, and health for individuals with
      stroke.
AB  - The current study evaluated the relationships among spiritual beliefs, religious
      practices, physical health, and mental health for individuals with stroke. A
      cross-sectional analysis of 63 individuals evaluated in outpatient settings,
      including 32 individuals with stroke and 31 healthy controls was conducted
      through administration of the Brief Multidimensional Measure of
      Religiousness/Spirituality (BMMRS) and the Medical Outcomes Scale-Short Form 36
      (SF-36). For individuals with stroke, the SF-36 General Mental Health scale was
      significantly correlated with only the BMMRS Religious and Spiritual Coping scale
      (r = .43; p < .05). No other BMMRS factors were significantly correlated with SF
      36 mental or physical health scales. Non-significant trends indicated spiritual
      factors were primarily related to mental versus physical health. This study
      suggests spiritual belief that a higher power will assist in coping with
      illness/disability is associated with better mental health following stroke, but
      neither religious nor spiritual factors are associated with physical health
      outcomes. The results are consistent with research that suggests that spiritual
      beliefs may protect individuals with stroke from experiencing emotional distress.

PMID- 19104989
TI  - When anxiety symptoms masquerade as medical symptoms: what medical specialists
      know about panic disorder and available psychological treatments.
AB  - Under-recognition of somatic symptoms associated with panic in primary care
      settings results in unnecessary and costly diagnostic procedures and
      inappropriate referrals to cardiologists, gastroenterologists, and neurologists.
      In the current study specialists' knowledge regarding the nature and treatment of
      panic were examined. One-hundred and fourteen specialists completed a
      questionnaire assessing their knowledge about panic attacks, including their
      perceptions of psychologists' role in treating panic. Respondents answered 51% of
      knowledge items correctly. Although most knew the definition of a panic attack,
      they knew less about clinical features of panic and its treatment. Specifically,
      whereas 97.4% believed medication effectively relieves panic symptoms, only 32.5%
      knew that cognitive-behavioral therapy (CBT) is a first-line treatment. Only 6%
      reported knowing how to implement CBT, and only 56.1% recognized that
      psychologists could effectively treat panic. These findings demonstrate
      significant gaps in specialists' knowledge about panic and the need to enhance
      physician knowledge about panic attacks and their treatment.

PMID- 19104990
TI  - CD4 count and physical symptoms among urban African American mothers with HIV: an
      examination of the role of optimism and depressive symptoms.
AB  - The current study examined the link between immune functioning (CD4 count) and
      physical symptoms, as well as the moderating role of optimism and depressive
      symptoms, in a sample of 99 low income, inner city African American women with
      HIV. Although there was no main effect of CD4 count on physical symptoms,
      depressive symptoms moderated the association between CD4 count and physical
      symptoms. More compromised immune functioning (lower CD4 count) was associated
      with more physical symptoms under conditions of higher levels of depressive
      symptoms, but not lower levels of depressive symptoms. This finding was observed
      using both a self-report measure and a clinician-rating of women's depressive
      symptoms. There were no main or interactive effects for optimism. Clinical
      implications and future research directions are presented.

PMID- 19104991
TI  - Introducing mindfulness to clinical psychologists in training: an experiential
      course of brief exercises.
AB  - A 14 session, structured, mindfulness skills group utilizing short (10 min)
      practices was undertaken by clinical psychologists in training as a voluntary
      lunchtime activity. The present study was a preliminary investigation into
      whether a short course of brief mindfulness exercises could facilitate the
      development of personal understandings of mindfulness without requiring a
      significant time commitment that might impinge upon participants' ability to take
      part. Quantitative and qualitative evaluations suggested that the course could be
      a useful experiential introduction to mindfulness for clinicians. The results
      also suggested that the format of frequent, brief exercises could have utility
      for conducting mindfulness-based training in time-limited environments but
      further research is required to examine the effects of frequency and duration of
      practice on the development of mindfulness skills.

PMID- 19104992
TI  - Temporomandibular Disorder in Brazilian patients: a preliminary study.
AB  - The objective of the current study was to evaluate disease-related beliefs,
      adherence to treatment, quality of life, coping strategies and cognitive status
      in a group of Brazilian patients with Temporomandibular Disorder (TMD). Thirty
      patients were evaluated with a semi-directed interview, the Coping Strategies
      Inventory, and a Mini-Mental State Examination. Although half (50%) of the
      patients had known their diagnosis long term, 40% of the sample were not
      correctly following proposed treatment. All patients had a similar pattern of
      pain behavior related to TMD, while disease-related beliefs, quality of life and
      coping strategies were variable. Expectations about treatment also had
      significant association with treatment adherence. The findings of this study
      suggest that a more thorough understanding of individual differences in TMD is
      warranted.

PMID- 19104996
TI  - Journal of Religion and Health. Editorial.

PMID- 19104997
TI  - An appraisal of psychological & religious perspectives of self-control.
AB  - The boundary between psychology and religion is at its murkiest around topics of
      interest to both forms of discourse. An attempt to clarify some of the boundary
      issues specifically present in discussions of self-control or self-regulation,
      this paper begins by examining self-control in healthy psychological functioning.
      Research on feedback loops, information processing and ego depletion have
      highlighted key psychological mechanisms involved in self-control. Next this
      paper explores common themes in religious perspectives regarding the virtue of
      self-control and self-restraint. A clear preoccupation of major religious
      traditions is the management of human passion and desire. In conclusion, three
      boundary concerns relevant to both psychology and religion are discussed: the
      meaning of virtue, differences in defining the self in self-control, and
      relational concerns important to understanding self-control.

PMID- 19104998
TI  - Feeling good, but lacking autonomy: closed-mindedness on social and moral issues
      in new religious movements.
AB  - According to previous research, New Religious Movements (NRMs) seem to have a
      positive effect on the mental health of members who join NRMs with some previous
      affective, cognitive or other vulnerabilities. The present study investigates the
      other, less positive, side of the psychology of NRMs, i.e. elements that may be
      an obstacle to optimal development, such as rigidity and low autonomy. In
      comparison to non-NRM members, members of various NRMs in Belgium (N = 120) were
      found to be low in quest religious orientation (Altemeyer and Hunsberger, Int J
      Psychol Religion 2:113-133, 1992), to privilege conservation values to the
      detriment of openness to change values (Schwartz, Advances in experimental social
      psychology (vol 25, pp. 1-65). Orlando, FL: Academic Press, 1992), to show
      submissiveness to authority in hypothetical situations (projective measure), and
      to highly moralize judgments of transgression relative to conventional domains
      (Turiel, The development of social knowledge: Morality and social convention.
      Cambridge: Cambridge University Press, 1983). Discussion points out the idea that
      rigidity and restriction of autonomy may be the price to be paid for the
      structuring role NRMs play with regard to previous vulnerabilities.

PMID- 19104999
TI  - The role of spirituality in advance directive decision making among independent
      community dwelling older adults.
AB  - The purpose of this grounded theory study, based on Strauss and Corbin's (1998)
      grounded theory methodology, was to investigate the meaning, definition, and
      needs regarding the role of spirituality in end of life care among independent
      community dwelling older adults in relation to advance directive decision making
      (ADDM). Findings revealed that through the use of story telling, independent
      community dwelling older adults were able to define spirituality and describe the
      important role spirituality plays in everyday life and in ADDM. A theoretical
      model was constructed consisting of a mirrored basic social process, Spirituality
      as Connecting.

PMID- 19105000
TI  - South African Muslim Faith Healers perceptions of mental illness: understanding,
      aetiology and treatment.
AB  - The important role that religious beliefs may have on perceptions of mental
      illness cannot be ignored. Many religions including Islam advocate witchcraft and
      spirit possession--all of which are thought to influence the behaviour of a
      person so as to resemble that of a mentally ill individual. Thus this research
      explored Muslim Faith Healers perceptions of mental and spiritual illness in
      terms of their understanding of the distinctions between the two, the aetiologies
      and the treatments thereof. Six Muslim Healers in the Johannesburg community were
      interviewed and thematic content analysis was used to analyse the data. From the
      results it is clear that the faith healers were aware of the distinction between
      mental and spiritual illnesses. It was also apparent that Islam has a clear
      taxonomy that distinguishes illness and the causes thereof. Treatments are then
      advised accordingly. Thus this paper argues that the predominant Western view of
      the aetiology and understanding of mental illness needs to acknowledge the
      various culturally inclined taxonomies of mental illness so as to better
      understand and aid clients.

PMID- 19105001
TI  - The effect of pastoral care services on anxiety, depression, hope, religious
      coping, and religious problem solving styles: a randomized controlled study.
AB  - This randomized controlled study measured the effect of chaplain interventions on
      coronary artery bypass graft (CABG) patients over time. One hundred sixty-six
      CABG patients, received pre- and post-surgery testing at 1 month and 6 months
      with four instruments. Five chaplain visits were made to the intervention group,
      the control group received none. Comparison scores for anxiety, depression, hope,
      positive and negative religious coping, and religious coping styles were
      analyzed. Significant difference was found between groups in positive religious
      coping (PRC) (p = .023) and negative religious coping (NRC) (p = .046) scores
      over time. PRC increased in intervention group, decreased in the control group
      while NRC decreased in intervention group and increased in the control group.
      Demographics were comparable between groups. Moderate chaplain visits (average
      total visits time, 44 min) may be effective in helping CABG patients increase
      positive religious coping and decrease negative religious coping.

PMID- 19105002
TI  - And all is always now: contemplations on artistic talent.
AB  - This paper aims to suggest the notion of layers of dying, as a metaphorical
      discussion of states that call for the breakdown of opposites and a unification
      in the form of a lived experience. Artistic talent is seen as a personal capacity
      to sustain such a state and transform it into a communicative form that is
      accessible to us all. Winnicott, in his "fear of breakdown" paper is a main
      source of influence, along with Bion who encouraged the articulation of "stray
      thoughts."

PMID- 19105003
TI  - The prodigal son: some psychological aspects of Augustine's conversion to
      Christianity.
AB  - Augustine's conversion is considered exemplary for its Christian testimony.
      However, the psychological aspects are also relevant, for Augustine's conversion
      to Christianity was as much inspired by personal and cultural ambitions as by
      religious convictions. For Augustine, the conversion to the Christian faith
      spelled a life of asceticism--a life of celibacy, a virtuous and chaste
      existence, which also offered him a means of escape from the threatening
      ambiguity of parental relations and a chance to realize the cultural ideal of the
      civilized philosopher who has subjugated the passions of the flesh. In this paper
      we explore the psychological dynamics of the absent father, the suffering mother
      and the prodigal son and the role they played in Augustine's conversion to
      Christianity.

PMID- 19105004
TI  - Spiritual exercises in Augustine's confessions.
AB  - Confessions, the narrative of Augustine's spiritual journey, has been a source of
      inspiration to readers through many centuries. It addresses the universal
      striving of the individual towards a 'way of living' characterized by internal
      coherence and an experience of the transcendent. Augustine, using a method of
      inquiry and engagement, guides the reader through some fundamental exercises:
      remembering one's story; facing inner restlessness; entering into dialogue with
      God; ordering of human love; centering in Christ; participating in a community of
      faith; living as a pilgrim. Together, they constitute a didactic instrument for
      the spiritual development of his readers. This paper reconstructs that central
      purpose in a coherent and practical model.

PMID- 19105005
TI  - Mother, melancholia, and dreams in Erik H. Erikson's Insight and Responsibility.
AB  - In an earlier article (Capps, 2007a) on Erik H. Erikson's earliest writings (1930
      1931) I focused on the relationship between the child's melancholia and conflict
      with maternal authority, and drew attention to the restorative role of humor. In
      a subsequent article (Capps, 2007b) on Erikson's Childhood and Society (1950) I
      explored the same theme of the relationship of melancholia and the mother, but
      focused on the restorative role of play. In this article drawing from his Insight
      and Responsibility (1964) I continue this exploration of the relationship of
      melancholia and the mother, but focus on the restorative role of dreams. In
      support of this understanding of dreams, I focus on Erikson's interpretation of
      one of Sigmund Freud's dreams in light of the first two stages of the life cycle,
      and his view that the dream itself is inherently maternal.

PMID- 19105006
TI  - J. Robert Oppenheimer: a faith development portrait.
AB  - J. Robert Oppenheimer was among the most important and enigmatic figures in 20th
      century science. He is best known for successfully directing the Manhattan
      Project that produced the first atomic bombs that were dropped on Japan at the
      end of World War II. Subsequently, he became a scientist and statesman who
      advised the United States government in the areas of atomic weapons development
      and public policy. He later became subject to an investigation in 1954 into his
      previous political affiliations and his personal behavior that ended in the
      revoking of his security clearance. This essay seeks to chronicle Oppenheimer's
      coming of age as a public intellectual with a view toward his own psychological
      history and most especially in relationship to the stages of faith development
      articulated by James Fowler and colleagues. Moreover, though not conventionally
      religious, Oppenheimer's life and thought were permeated with themes and ideas of
      a religious and ethical nature that shaped his adult character and informed his
      view of the world. This essay was originally presented at The Richardson History
      of Psychiatry Research Seminar at Weill Cornell Medical College.

PMID- 19105007
TI  - The Journal of Religion and Health exists to support interdisciplinary and
      multidisciplinary exploration of the nature of religion.

PMID- 19105009
TI  - The role of culture in the relationship between religiosity and psychological
      well-being.
AB  - Several measures of religious practice and religious orientation
      (intrinsic/extrinsic/quest) and two measures of psychological well-being
      (positive affect and negative affect) have been employed in a cross-cultural
      survey of undergraduate university students from five different
      cultural/religious environments: Slovenia, Bosnia and Herzegovina, Serbia, the
      United States of America, and Japan. Results suggest that measures of exstrinsic,
      intrinsic, and quest religiosity are not entirely applicable in most of the
      cultures observed. Nevertheless, it was possible to discern abbreviated cross
      culturally valid scales for each dimension. The strength and direction of the
      correlation between psychological well-being and a particular type of religious
      orientation proved to depend substantially upon culture. More importantly, the
      cultural environment plays a crucial role in shaping the relationship between
      general measures of religiosity and psychological well-being. According to the
      data, higher general levels of religiosity at the societal level are linked to
      more positive correlations between religiosity and psychological well-being. The
      overall picture leads to the conclusion that there is no culturally universal
      pattern in the relationship between measures of religiosity and psychological
      well-being and that the particular cultural and religious context should always
      be considered in studies dealing with this issue.

PMID- 19105008
TI  - Measuring religiousness in health research: review and critique.
AB  - Although existing measures of religiousness are sophisticated, no single approach
      has yet emerged as a standard. We review the measures of religiousness most
      commonly used in the religion and health literature with particular attention to
      their limitations, suggesting that vigilance is required to avoid over
      generalization. After placing the development of these scales in historical
      context, we discuss measures of religious attendance, private religious practice,
      and intrinsic/extrinsic religious motivation. We also discuss measures of
      religious coping, wellbeing, belief, affiliation, maturity, history, and
      experience. We also address the current trend in favor of multi-dimensional and
      functional measures of religiousness. We conclude with a critique of the
      standard, "context-free" approach aimed at measuring "religiousness-in-general",
      suggesting that future work might more fruitfully focus on developing ways to
      measure religiousness in specific, theologically relevant contexts.

PMID- 19105010
TI  - Chronic pain and praying to a higher power: useful or useless?
AB  - In the present study a Swedish sample of 118 persons with chronic pain completed
      online tests on two occasions in association with treatment trials. A three item
      subscale measuring praying as a coping strategy was derived from the Coping
      Strategies Questionnaire (CSQ), but adapted to refer to "a higher power" instead
      of "God". Measures of pain and anxiety/depression were also included. Results
      revealed significant associations between praying and pain interference and
      impairment. Praying was also associated with anxiety and depression scores.
      Results also showed that prayer predicted depression scores at follow-up, and
      that follow-up prayer was predicted by pain interference at first measurement
      occasion. Overall, if prayer had any relation with the other variables it was in
      the negative direction of more distress being associated with more praying both
      concurrently and prospectively.

PMID- 19105011
TI  - Assessing belief in the 10 commandments: the multidimensional 10 commandments
      questionnaire.
AB  - Instruments designed to assess various aspects of religion are widespread, but
      few have been constructed to assess specific religious values and beliefs. The
      purpose of the present research was to address this limitation by providing
      preliminary evidence for the reliability and validity of the Multidimensional 10
      Commandments Questionnaire (M10CQ), a self-report instrument that measures belief
      in the 10 Commandments. Data from three separate samples provided evidence
      supporting the reliability (i.e., internal consistency) of the M10CQ subscales.
      Other results indicated that women endorsed many of the 10 Commandments more
      strongly than men, and that various Commandments predicted people's mental health
      (less hostility), their parenting style (more authoritarian and authoritative
      parenting), and their interpersonal attachments (a more trusting bond with
      others). The findings reported in this research help to identify the ways in
      which religious values and beliefs are integrated with multiple aspects of
      people's lives. The discussion highlights the usefulness of the Multidimensional
      10 Commandments Questionnaire (M10CQ) for studying religious beliefs and values.

PMID- 19105012
TI  - Religiousness and college student alcohol use: examining the role of social
      support.
AB  - The purpose of this study was to examine the mediating role of social support in
      the relationship between religiousness and alcohol use in a sample of college
      students. Two dimensions of religiousness: religious commitment and religious
      coping were examined as predictors of alcohol use. Participants were male and
      female college students (N = 221); the majority of the sample was Christian
      (73.8%). Emotional social support was tested as a mediator. Both religiousness
      dimensions and emotional social support were related to less frequent alcohol
      use; however, mediation was not supported. These findings indicate that religious
      commitment and dispositional religious coping are protective against alcohol use,
      yet social support does not account for this relationship.

PMID- 19105014
TI  - The holistic way: John Wesley's practical piety as a resource for integrated
      healthcare.
AB  - In the midst of the multifarious healthcare of the 21st century an Anglican
      clergyman from the 18th century named John Wesley can serve as a valuable
      resource for contemporary Christians seeking to faithfully live a life of well
      being which incorporates different forms of medicine. In order to explore
      Wesley's contributions to integrative care this essay will first situate Wesley
      in his 18th century context-a time period not completely unlike our own in which
      medicine was also experiencing dramatic shifts in practice and philosophy. In
      order to demonstrate his integration of the medical knowledge of his day the
      essay will look at Wesley's own medical practices and his relationships to
      physicians as forging a "middle way" between physic and empiricism. The essay
      will examine Wesley's theology as a practical piety which is grounded in a
      holistic sotieriology that sustains an integrative medicine (caring for body,
      mind, and spirit). Finally, the essay concludes with possibilities for integrated
      medicine in our own day as informed by a Wesleyan "way" of holistic practice.

PMID- 19105013
TI  - Influence of church attendance and spirituality in a randomized controlled trial
      to increase mammography use among a low-income, tri-racial, rural community.
AB  - Background The influence of church attendance and spirituality on mammography use
      was studied among Native American, White, and African American women living in a
      rural county. Methods A randomized trial was conducted to increase mammography
      use. Women (n = 851) were randomly assigned to receive either an educational
      program delivered by a lay health advisor or a physician letter and brochure
      about cervical cancer screening (control group). Church attendance and
      spirituality were measured at baseline and mammography use was evaluated 12
      months after enrollment using medical record review. Results Almost two-thirds of
      the women reported that they attended church at least once a week, and less than
      4% were classified as having low spirituality. Church attendance (P = 0.299) or
      spirituality (P = 0.401) did not have a significant impact on mammography use.
      Conclusions Church attendance and spirituality did not impact mammography use.

PMID- 19105015
TI  - An antiseptic religion: discovering a hybridity on the flux of hygiene and
      Christianity.
AB  - An antiseptic religion is a form of Protestant Christianity that was shaped in
      the context of colonization in Korea. This term was coined to explain a religious
      hybrid that was produced by the intermingling of American Evangelical Protestant
      Christianity, the concept of hygiene (germ theory) and indigenous Korean
      religiosity. This research deals with a historical process of making 'a
      medicalized religion' in Asia from a perspective of postcolonialism. Most of the
      early American Protestant missionaries in Korea were medical doctors who were
      influenced by the Germ theory of illness and considered Western medicine as an
      efficient tool to evangelize the country. As a result of their mission, a
      religious culture which emphasized washing away sins from the soul as analogous
      to washing away germs from the body was born. In addition, the Korean people
      developed a very unique form of public bathing ritual centered in the development
      of public baths to alleviate anxiety and to destabilize the solid strategies of
      the Japanese and the Americans, the two major colonial powers in Korea's history
      in the late 19th century.

PMID- 19105016
TI  - Prayer as therapeutic process toward aliveness within a spiritual direction
      relationship.
AB  - This article underscores the potential benefit of a specific form of Christian
      prayer that creates space within a spiritual direction relationship for the
      creation of inner images that reveal a person's unconscious relational longings
      and co-created representations of God. In this specific type of prayer that can
      be facilitated by mental health professionals and pastoral counselors, imagery of
      God's presence is created in the space between a Christian spiritual director and
      a Christian directee while they are open to inner experiences that reveal God's
      presence interacting with infantile processes toward aliveness. Aliveness is
      understood using Winnicottian notions in dialog with theories proposed by Allan
      N. Schore, affective neuropsychologist and Clinical Faculty at UCLA David Geffen
      School of Medicine, Ann Belford Ulanov, Jungian Analyst and Professor of
      Psychiatry and Religion at Union Theological Seminary and W.R.D. Fairbairn,
      [added] British psychoanalyst in the Objects Relations School. Ideas of
      transitional space, good enough mother, holding environment, aggression,
      creativity, and play are set alongside theories of affect regulation, the
      developing brain, co-created objective God images, the relational nature of God
      and being received as good while illuminating three prayer experiences during one
      30-year-old Asian American woman's 16-month therapeutic process toward aliveness.

PMID- 19105018
TI  - The metallic womb.
AB  - This study of malevolent narcissism examines the relationship between the
      Washington Snipers, Muhammad and Malvo, from the perspectives of attachment
      theory and Kleinian theory. Muhammad embodied a perverted understanding of
      manliness. Malvo was desperate for the love of a father, and fused with the
      omnipotent destructiveness of John Muhammad. Together they embarked on a failed
      Quest, recreating the original infant/caregiver scenario, which in their
      experience was about destruction and death, rather than gratitude and life. Malvo
      and Muhammad were perfect together, merged into one unit devoted to murder. Their
      victims were random and multiple, like their early caregivers.

PMID- 19105019
TI  - It is what I would call the correlational impulse.

PMID- 19105020
TI  - Spirituality as a resiliency quality in Xhosa-speaking families in South Africa.
AB  - The purpose of this qualitative study was to explore spirituality as a
      characteristic of family resilience in Xhosa-speaking families in South Africa. A
      parent, and in some cases an adolescent, represented each of the 51 families that
      participated. Participants were expected to respond to three open-ended questions
      regarding their family and identify factors or strengths that had recently helped
      their family. The results indicate that spirituality is an important coping
      resource. The core theme of spirituality consists of six related categories that
      facilitated the successful adaptation of the participating families after a
      crisis. These categories are Gifts from God; Guidance; God's Works; God's Plan;
      Prayer; and Faith.

PMID- 19105021
TI  - Cultural influences in the aetiological beliefs of saudi arabian primary care
      patients about their symptoms: the association of religious and psychological
      beliefs.
AB  - OBJECTIVE: To develop a self-report questionnaire to measure the beliefs of
      Arabic primary care patients about the causes of their physical symptoms; to use
      this to quantify the beliefs of patients consulting their general practitioners
      (GPs) in Saudi Arabia; and to test whether patients with psychological problems
      differ from others in their beliefs, particularly religious and supernatural
      beliefs. METHODS: Consecutive patients (N = 224) completed a specially developed
      aetiological beliefs' questionnaire. Patients were divided into two groups (cases
      and non-cases of emotional disorder) according to the GHQ-12. RESULTS: Religious
      and supernatural aspects of culture colour patients' symptom beliefs: that their
      symptoms were a test or punishment from Allah' was the most common belief. Even
      in non-cases, around half the patients also endorsed nerves and stress as a cause
      of their physical symptoms. Cases were more likely than non-cases to endorse
      items related to both religious and psychological factors. CONCLUSION: There is
      no support for the view that Saudi Arabian patients explain symptoms
      supernaturally as a way of denying psychological factors. GPs and health
      professionals in Saudi primary care need to understand what patients believe to
      be the cause of their problems and to appreciate that religious and psychological
      beliefs are both very common. GPs should address psychological beliefs and
      concerns even with those patients who present physical symptoms.

PMID- 19105022
TI  - Saints and sinners: training Papua New Guinean (PNG) Christian Clergy to respond
      to HIV and AIDS using a model of care.
AB  - Papua New Guinea has experienced a growing HIV/AIDS epidemic. The Christian
      Churches have played a vital role in responding to HIV, through community
      support, encouragement and social change. Strong, effective Church leadership can
      help create safe environments of care and support for those infected and for
      prevention of HIV. Method A series of trainings in capacity development for
      clergy were undertaken by the National AIDS Council Secretariat (NACS)/National
      HIV/AIDS Support Project (NHASP). Results A model "Church's Response to HIV and
      AIDS in a Care Continuum" was developed to assist the training. This paper
      discusses the model and the lessons learned.

PMID- 19105023
TI  - Longing for health. A practice of religious healing and biomedicine compared.
AB  - The standard notion is that biomedicine and religious healing are two completely
      different practices in modern Western societies. In this article, this notion is
      questioned by comparing in the Netherlands one practice of religious healing,
      namely the 'Services of salvation and healing' of the Pentecostal Levensstroom
      gemeente (Livingstream Church) of Jan Zijlstra, and one practice of biomedicine,
      namely the Antoni van Leeuwenhoek Cancer Hospital (AvL). What are the differences
      and possible similarities between these two? Starting from a cultural approach
      and after the description of these two practices, they are compared with respect
      to four points: concepts and objects, means and methods, 'healers' and patients,
      and effects and expectations. It is argued that these practices have at least
      five principle points in common: a tendency to objectivation of the underlying
      framework, a very instrumental way of working, 'healers' with a high ascribed
      status, efficacy along the indirect line of symbolic healing, and a comparable
      way of dealing with unknown and uncontrolled forces. What can these practices
      learn from each other?

PMID- 19105024
TI  - One mind or two? How psychiatrists and psychologists reconcile faith and science.
AB  - Utilizing qualitative interviews, this study showed how, to what extent, and why
      psychiatrists and psychologists of Judeo-Christian religious orientations or
      nonaffiliated believers in Michigan were willing or reluctant to integrate
      religious paradigms in their mental health practices. Most of the study
      participants were found to believe that medical-scientific and religious
      paradigms are equally important and may coexist or even be integrated in
      psychotherapeutic practice. However, actual attempts to integrate them usually
      reflected the practitioners' personal religious backgrounds and initiatives
      and/or were client driven. Yet these integration initiatives were found to face
      powerful institutional impediments such as politico-cultural norms of separation
      of religion from secular institutions and professional norms.

PMID- 19105025
TI  - The purpose and neurobiology of theory of mind functions.
AB  - Theory of Mind (ToM) refers to a cognitive process which allows an individual to
      "place him/herself" in the other person's "mind," so as to comprehend the
      latter's cognitive and emotional status, so as to predict his/her behavior and
      emotional response to a particular situation. ToM is necessary for everyday
      interaction among individuals and accounts for such human traits as empathy,
      compassion, and deceit. It is also particularly important in the relationship
      between a healer and his or her client, as well as in the God-human relationship.
      Recent research in the area of neurosciences has identified a specific brain
      "system" responsible for ToM, as well as described how these functions may be
      affected in certain neuropsychiatric conditions. In this article, we discuss the
      definition and neurobiological substrate of ToM. In addition, we discuss the
      cognitive steps important to achieve an "accurate" theory of mind, its relevance
      to "self-knowledge," and its limitations. We also review some of the data
      concerning abnormalities and "distortion" of ToM in neuropsychiatric disorders
      and aberrant human behavior.

PMID- 19105026
TI  - Have we found the holy grail? Theory of mind as a unifying construct.
AB  - Theory of Mind (ToM) refers to a person's ability to understand that another
      person has his or her own unique way of thinking and feeling. ToM is a well-known
      and rapidly expanding field of research in the neurosciences, cognitive, social
      sciences, evolution, and brain imaging. This review article expands ToM into
      areas where there has not yet been research. We propose that ToM could illuminate
      the relationship between religion/spirituality and health, and could provide the
      lingua franca for the hundreds of schools of psychotherapy. We discern two
      different kinds of spirituality: personal versus impersonal. Empathy is central
      to ToM research and is also central to mental health training and practice. ToM
      illuminates familiar topics in a new light. For example ToM reveals a close link
      between psychology and spirituality in self-efficacy and locus of control
      research.

PMID- 19105027
TI  - Redemptive experience in relational family therapy: a Christian perspective.
AB  - We all long for relationships with others, because only in connecting with others
      can we develop our intrapsychic structure and become functional adults. We are
      psychologically predisposed to have a constant connection with others and are
      driven toward relationships with others. Our deepest yearnings are therefore
      devoted to building solid dialogue as the means of becoming fully human. We,
      therefore, consciously or unconsciously, long for a relationship where we can
      experience happiness, satisfaction and, above all, redemption or salvation from
      our dreads, miseries and unhappiness. In this article we presuppose that a
      therapeutic relationship, demonstrated in a psychoanalytic setting, namely in
      relational family therapy, can contain redemptive dimensions in which the
      inextinguishable longing for salvation is always present.

PMID- 19105028
TI  - Pathologies of desire and duty: freud, ricoeur, and castoriadis on transforming
      religious culture.
AB  - This article emphasizes an underappreciated aspect of Freud's critique of
      religion taken up in the writings of Ricoeur and Castoriadis: the degree to which
      pathologies of desire and duty imbue our relation to shared cultural forms, i.e.,
      narratives, ideals, and values. Both thinkers find in Freud's anti-religious
      polemic a valuable attempt to address the intransigence, fanaticism, and violence
      that can result from an unreflected affirmation of Tradition. Alongside
      developing a respect and acceptance of other cultures, they argue for the need to
      establish a critical relation to 'sacred'meaning structures, one that mirrors
      interpretive strategies within the psychoanalytic process. Ricoeur and
      Castoriadis critique Freud's accentuation of neurosis while extending his
      thinking into personal-philosophical and social-political contexts.

PMID- 19105029
TI  - Mother, melancholia, and humor in Erik H. Erikson's earliest writings.
AB  - Erik H. Erikson wrote three articles when he was in his late-twenties and an up
      and-coming member of the psychoanalytic community in Vienna. At the time he wrote
      these articles, he was in a training psychoanalysis with Anna Freud, teaching at
      the Heitzing School in Vienna, and learning the Montessori method of teaching.
      These articles focus on the loss of primary narcissism and the development of the
      superego (or punitive conscience) in early childhood, especially through the
      child's conflict with maternal authority. They support the idea that melancholia,
      with its internalized rage against the mother, is the inevitable outcome of the
      loss of primary narcissism. I note, however, that the third of these articles
      makes a case for the restorative role of humor, especially when Freud's view that
      humor is a function of the superego is taken into account.

PMID- 19105031
TI  - Arsenic uptake and speciation in vegetables grown under greenhouse conditions.
AB  - The accumulation of arsenic (As) by vegetables is a potential human exposure
      pathway. The speciation of As in vegetables is an important consideration due to
      the varying toxicity of different As species. In this study, common Australian
      garden vegetables were hydroponically grown with As-contaminated irrigation water
      to determine the uptake and species of As present in vegetable tissue. The
      highest concentrations of total As were observed in the roots of all vegetables
      and declined in the aerial portions of the plants. Total As accumulation in the
      edible portions of the vegetables decreased in the order radish >> mung bean >
      lettuce = chard. Arsenic was present in the roots of radish, chard, and lettuce
      as arsenate (As(V)) and comprised between 77 and 92% of the total As present,
      whereas in mung beans, arsenite (As(III)) comprised 90% of the total As present.
      In aerial portions of the vegetables, As was distributed equally between both
      As(V) and As(III) in radish and chard but was present mainly as As(V) in lettuce.
      The presence of elevated As in vegetable roots suggests that As species may be
      complexed by phytochelatins, which limits As translocation to aerial portions of
      the plant.

PMID- 19105030
TI  - Cloning and characterization of a novel CBL-interacting protein kinase from
      maize.
AB  - A novel CBL-interacting protein kinase (CIPK) gene, ZmCIPK16, was isolated from
      maize (Zea mays), which has been certified to have two copies in the genome. The
      ZmCIPK16 is strongly induced in maize seedlings by PEG, NaCl, ABA, dehydration,
      heat and drought, but not by cold. A yeast two-hybrid assay demonstrated that
      ZmCIPK16 interacted with ZmCBL3, ZmCBL4, ZmCBL5, and ZmCBL8. Bimolecular
      fluorescence complementation (BiFC) assays prove that ZmCIPK16 can interact with
      ZmCBL3, ZmCBL4, ZmCBL5, and ZmCBL8 in vivo. Subcellular localization showed that
      ZmCIPK16 is distributed in the nucleus, plasma membrane and cytoplasm; this is
      different from the specific localization of ZmCBL3, ZmCBL4, and ZmCBL5, which are
      found in the plasma membrane. The results also showed that overexpression of
      ZmCIPK16 in the Arabidopsis sos2 mutant induced the expression of the SOS1 gene
      and enhanced salt tolerance. These findings indicate that ZmCIPK16 may be
      involved in the CBL-CIPK signaling network in maize responses to salt stress.

PMID- 19105032
TI  - Principles and application of an in vivo swine assay for the determination of
      arsenic bioavailability in contaminated matrices.
AB  - The assessment of arsenic (As) bioavailability from contaminated matrices is a
      crucial parameter for reducing the uncertainty when estimating exposure for human
      health risk assessment. In vivo assessment of As utilising swine is considered an
      appropriate model for human health risk assessment applications as swine are
      remarkably similar to humans in terms of physiology and As metabolism. While
      limited in vivo As bioavailability data is available in the literature, few
      details have been provided regarding technical considerations for performing in
      vivo assays. This paper describes, with examples, surgical, experimental design
      and analytical issues associated with performing chronic and acute in vivo swine
      assays to determine As bioavailability in contaminated soil and food.

PMID- 19105033
TI  - Flow cytometry, with double staining with Nile red and anti-CD3 antibody, to
      detect phospholipidosis in peripheral blood lymphocytes of rats treated with
      amiodarone.
AB  - A flow cytometry method, to monitor peripheral lymphocytes phospholipidosis, has
      been set up using a single staining with Nile red and double staining with Nile
      red and anti-CD3 monoclonal antibody. Blood has been collected from rats treated
      with amiodarone (phospholipidogenic antiarrhythmic drug). By flow cytometer, it
      is possible to detect phospholipids, using Nile red, a probe for intracellular
      lipids staining, changing its fluorescence on the stained lipid basis. CD3
      antigen has been selected to focus on T cells, to evaluate whether these cells
      are the target of phospholipidosis amiodarone-dependent. In the study A, Sprague
      Dawley rats were treated with three different doses (75, 150, and 300 mg kg(-1)
      day(-1)) of amiodarone or vehicle alone, for 14 days, followed by 14 days of
      recovery: Data obtained show that by flow cytometry, with Nile red alone, it is
      possible to detect a dose- and time-related response of phospholipidosis-positive
      lymphocytes; a partial recovery is also assessed. In the study B, Sprague-Dawley
      rats were treated with a single dose (300 mg kg(-1) day(-1)) of amiodarone, for
      14 days: Data obtained show that animals treated with amiodarone have a
      significant increase of phospholipidosis-positive lymphocytes (p = 0.008), in
      particular of CD3+ cells (p = 0.0056). Transmission electron microscopy analysis
      confirmed data obtained by flow cytometry. This work shows that flow cytometry
      with Nile red could be a good tool to monitor ex vivo phospholipidosis in
      lymphocyte cells of animals treated with amiodarone: The phospholipidogenic
      effect is more evident focusing on CD3+ T lymphocytes, thus suggesting that these
      cells are probably the target of phospholipidosis.

PMID- 19105034
TI  - Microdissection and chromosome painting of X and B chromosomes in Locusta
      migratoria.
AB  - Acquisition of knowledge of the nature and DNA content of B chromosomes has been
      triggered by a collection of molecular techniques, one of which, microdissection,
      has provided interesting results in a number of B chromosome systems. Here we
      provide the first data on the molecular composition of B chromosomes in Locusta
      migratoria, after microdissection of the B and X chromosomes, DNA amplification
      by one (B) or two (X) different methods, and chromosome painting. The results
      showed that B chromosomes share at least two types of repetitive DNA sequences
      with the A chromosomes, suggesting that Bs in this species most likely arose
      intraspecifically. One of these repetitive DNAs is located on the heterochromatic
      distal half of the B chromosome and in the pericentromeric regions of about half
      of the A chromosomes, including the X. The other type of repetitive DNA is
      located interspersedly over the non-centromeric euchromatic regions of all A
      chromosomes and in an interstitial part of the proximal euchromatic half of the B
      chromosome. Chromosome painting, however, did not provide results sufficiently
      reliable to determine, in this species, which A chromosome gave rise to the B;
      this might be done by detailed analysis of the microdissected DNA sequences.

PMID- 19105035
TI  - The paracentric inversion In(2Rh)PL alters the centromeric organization of
      chromosome 2 in Drosophila melanogaster.
AB  - Centromeres are complex structures involved in an evolutionarily conserved
      function, the correct segregation of chromosomes and chromatids during meiosis
      and mitosis. The centromere is determined by epigenetic processes that result in
      a particular nucleosome organization (CEN chromatin) that differs from the rest
      of the chromatin including the heterochromatin that normally surrounds the
      centromere in higher organisms. Many of the current models of centromere origin
      and organization rely on the molecular and cytological characterization of
      minichromosomes and their derivatives, and on studies on the origin and
      maintenance of neocentromeres. Here, we describe the peculiar centromere
      organization observed in In(2Rh)PL, a paracentric D. melanogaster inversion in
      which the centromere is maintained in its natural context but is directly flanked
      by a euchromatic domain as a result of the rearrangement. We have identified the
      breakpoints of the inversion and show that the proximal one is within the
      centromere region. The data presented suggest that, notwithstanding the loss of
      all the pericentric 2Rh heterochromatin, the centromere of the In(2Rh)PL
      chromosome is still active but presents a nucleosomal organization quite
      different from the organization usually observed in the centromeric region.

PMID- 19105036
TI  - Osteoprotegerin and RANKL differentially regulate angiogenesis and endothelial
      cell function.
AB  - Osteoprotegerin (OPG) a soluble tumor necrosis factor receptor family molecule
      protects endothelial cells from apoptosis in vitro and promotes
      neovascularization in vivo. In this study, we assessed the role of OPG and its
      ligands, receptor activator of nuclear factor-kappaB ligand (RANKL) and tumor
      necrosis factor-related apoptosis inducing ligand (TRAIL), in microvessel
      formation using the rat aortic ring model of angiogenesis. OPG was found to
      promote a twofold increase in angiogenic sprouting in the aortic ring model, and
      this effect was inhibited by pre-incubation with a fivefold molar excess of
      either RANKL or TRAIL. While TRAIL had no effect upon angiogenesis on its own,
      RANKL was found to potently inhibit basal and vascular endothelial growth factor
      induced angiogenesis. OPG increased the rate of endothelial cell proliferation in
      sprouting microvessels; in contrast, RANKL inhibited proliferation. RANKL was
      found to induce endothelial apoptosis at days 6, 7, and 10 in the aortic ring
      model and after incubation with human umbilical vein endothelial cells (HUVECs).
      Signaling studies showed that OPG induced ERK1/2 and Akt phosphorylation in
      HUVECs while RANKL had no effect. Our results indicate that OPG is a positive
      regulator of microvessel formation, while RANKL is an angiogenic inhibitor due to
      effects on regulation of endothelial cell proliferation, apoptosis, and
      signaling.

PMID- 19105037
TI  - Hydrogeochemical data as a tool for exploration and mapping: a case study from
      part of Afikpo Basin southeastern Nigeria.
AB  - Fourteen (14) characters from six (6) water samples collected from springs,
      ponds, and streams located in Lower Cretaceous sedimentary area of Afikpo Basin
      have been analyzed. These include pH, turbidity, conductivity, total dissolved
      solid, hardness, Fe2+, Ca2+, Mg2+, K+, NO3-, Cl-, SO4(2-), and Na+. These
      sediments, which are Turonian and Coniacian in age, are subdivided into two by a
      basic rock dyke. Results of the analyses show clearly that the Turonian
      sediments, intruded by dolerite, have net Fe2+, HCO3-, Ca2+, Mg2+, Mn2+, Cl-, and
      SO4(2-) concentration while those from the younger Coniacian sediment have net
      higher amounts of K+, Na+, and Mn2+. The overriding mafic minerals in the basic
      intrusive rock possibly led to higher leaching into ground water system near it.
      On the other hand, the presence of feldsparthic to kaolinitic sands of the
      younger Coniacian units led to higher K+ and Na+ matter in the water from these
      zones. The formations dip away from the older sediments. Concentrations of these
      characters are within acceptable drinking water standards by World Health
      Organization but noticeable anomalous zones for Fe2+, Mg2+, and Ca2+ are zones of
      basic rock suites. Areas with greater Na+ and K+ are traceable to sandy units. It
      is thus concluded that more analysis of surface, subsurface, and pond water
      samples can be utilized for minerals search and geological mapping. At this
      stage, it forms a veritable reconnaissance tool.

PMID- 19105038
TI  - The role of forest stand density in controlling soil erosion: implications to
      sediment-related disasters in Japan.
AB  - The role of forest stand density in controlling soil erosion was investigated in
      Ehime Prefecture, Japan. The main objective was to compare soil erosion under
      different forest conditions including forest type, species composition, and stand
      density as influenced by thinning operations. Relative yield index (Ry) was used
      as an indicator of stand density to reflect the degree of management operations
      in the watershed. Eleven treatments were established based on the above forest
      conditions. Soil loss was collected in each of the 11 treatments after each
      rainfall event for a period of 1 year. The paper presents summary data on soil
      loss as affected by forest conditions and rainfall patterns. Findings showed that
      an appropriate forest management operation, which can be insured by stand density
      control, is needed to reduce soil loss. The present study plays an important role
      in clarifying technical processes related to soil erosion, while it helps linking
      these elements to current Japanese forestry issues and bringing new inputs to
      reducing sediment-related disasters in Japan.

PMID- 19105040
TI  - The seasonal status of chemical parameters in shallow coastal aquifers of
      Rameswaram Island, India.
AB  - The study area Rameswaram, a holy island, is famous for the sacred Ramanathaswamy
      temple, which cements people of the country regardless of their place, residence,
      or their religion or creed. This coastal tract is experiencing a chronic fresh
      water shortage, despite a few spring sources. The study area is selected for the
      characterization of physico-chemical parameters viz., pH, EC, TDS, salinity, TA,
      TH, CH, MH, chloride, and fluoride for 150 groundwater samples and the impact of
      pre- and post-monsoons on the groundwater quality is studied. The water quality
      index advocates the transfer of groundwater quality from unacceptable status in
      the pre-monsoon into an acceptable status in the post-monsoon. The Langelier
      saturation index reflects the scaling tendency of groundwater in the study area.
      The Karl Pearson correlation matrix has approved the maximum influence of calcium
      and chloride on the total dissolved solids. It is interesting to conclude that
      the groundwater in the study area has very had nature, especially of non
      carbonate type.

PMID- 19105039
TI  - Characterization of metal aerosols in PM10 from urban, industrial, and Asian Dust
      sources.
AB  - Metallic elements (As, Be, Ca, Cd, Co, Cr, Fe, K, Mn, Ni, Pb, Sb, Se, and Zn) in
      PM10 aerosols were determined at urban and industrial sites, which are affected
      by traffic and residential sources, metallurgical activity, and petrochemical and
      steel works. The effect of the long-range transported Asian Dust on the metal
      content of aerosols was also examined. At the urban sampling site, concentrations
      of As, Cd, Pb, Se, and Zn were assigned to road traffic and combustion sources,
      Ca and Fe to soil dust sources from long-range transported Asian Dusts, and Cr
      and Ni to metallurgical sources transported from the nearby industrial complex,
      based on Principal Component Analysis (PCA). Enhanced Cr and Ni concentrations at
      the metallurgical industrial site suggest that local emissions from metal
      assembly facilities and manufacture of alloys contributed to elevated levels of
      those metals. We also observed that petrochemical activities contributed to
      increased levels of Sb and Zn. When Asian Dust events occurred, Ca, Fe, K, and Zn
      concentrations dramatically increased compared to values without the Asian Dust.
      Two different types of Asian Dust events were observed. For the Asian Dust event
      1 (4/1/2007), the Fe and K concentrations were much higher by a factor of 2-3
      than those for the Asian Dust event 2 (3/2/2008), while As, Mn, and Zn
      concentrations were significantly higher on the Asian Dust event 2. Backward
      trajectory analysis showed that for the Asian Dust event 2, the air mass had
      passed over the heavily industrialized zones in China during long-range transport
      to the current sampling site, suggesting that the As, Mn, and Zn may have
      originated from industrial sources.

PMID- 19105041
TI  - Nutritional composition of three fodder species browsed by camels (Camelus
      dromedarius) on arid area of Tunisia.
AB  - Browsing camels have access to different plant species in relation to the kind of
      pasture they can reach. A study was conducted in an arid region of Southern
      Tunisia to determine the dietary preference and forage quality of free ranging
      camels. Foliage consisting of leaves from Limonium pruinosum, Retama raetam and
      Stipa tenacissima, was collected during the dry season to evaluate the chemical
      characteristics and nutritional value of these browse fodder species. The dietary
      preference was studied using 15 adult camels which were selected from a herd of
      50 animals appropriately marked for identification. There was a significant
      difference in the chemical composition and nutritional value of plant species
      collected. Based on crude protein (CP) content and nutritional value, the three
      fodder species browsed can be recommended as good-quality food source for camels
      under pastoral management.

PMID- 19105042
TI  - Changes in colostrum of Murrah buffaloes after calving.
AB  - Colostrum samples were collected from 8 Murrah buffaloes on days 1, 2, 3, 4 and 5
      after calving. Levels of IgG averaged 54.0 mg/ml at calving, then decreased
      significantly (P < 0.01). IgA and IgM on day 1 were 3.22 mg/ml and 5.22 mg/ml,
      respectively; both decreased during the first five days after calving. Values of
      IgA and IgM were higher than those reported in cows. SCC values, which were high
      at calving (500,000 per ml), reduced significantly (P < 0.01) on day 2, then
      decreased slightly until day 5 (180,000 per ml). At calving, macrophages were the
      most prominent cells in buffalo colostrum, followed by lymphocytes and
      neutrophils. Phagocytic activity was 23% at calving and reduced significantly (P
      < 0.01) to 14% on day 5. Phagocytic index was highest in the first colostrum, and
      then decreased non-significantly.

PMID- 19105043
TI  - Hydatidosis of slaughtered animals in Ngorongoro district of Arusha region,
      Tanzania.
AB  - A study on the prevalence of hydatidosis in cattle, goats and sheep was carried
      out in Ngorongoro district of Arusha region, Tanzania. A 4-years data records
      from four slaughter slabs were retrieved and analysed. In addition, meat
      inspection was done in the same slaughter slabs for nine months and 64 households
      were interviewed to assess the community awareness on hydatidosis. Results showed
      the overall prevalence of hydatidosis to be 47.9%. Species prevalence of 48.7%,
      34.7% and 63.8% in cattle, goats and sheep respectively was recorded. Of 174
      cysts examined in cattle, 37 (21.3%) were fertile, 126 (72.4%) were sterile and
      11 (6.3%) were calcified. Out of 215 goats and 67 sheep cysts examined, 52
      (24.7%) and 26 (38.8%) were fertile, 138 (64.2%) and 38 (56.7%) were sterile, 24
      (11.2%) and 3 (4.5%) were calcified respectively. The higher percentage of
      fertile hydatid cysts in sheep and goats coupled with the practice of backyard
      slaughter of sheep and goats suggests that, these animals could be important
      intermediate hosts for the maintenance of the domestic life cycle of E.
      granulosus in the locality. Questionnaire survey revealed that 17.2% of the
      respondents were aware of hydatidosis but non of them were knowledgeable on its
      transmission. Up to 84.4% of the respondents had domestic ruminants and donkeys,
      while 89.1% had dogs. Of the households with dogs, only 19.3% had their dogs
      dewormed at least once in life time. Most of the households (87.7%) had their
      dogs managed freely and 77.2% of the respondents reported school children to be
      the closest friends of dogs in the family. The prevalence of E. granulosus
      infection in wildlife and the possible relationship of the domestic cycle to the
      sylvatic cycle operating in the same area are unknown and need to be studied.

PMID- 19105044
TI  - Paternity assessment: application on estimation of breeding value in body-weight
      at first egg trait of egg-laying duck (Anas platyrhynchos).
AB  - Paternity index was analyzed using five microsatellite loci among Chinese egg
      laying ducks (Anas platyrhynchos). Based on the paternity relationship that was
      identified by paternity index analysis, the estimated breeding value (EBV) was
      calculated using BLUP (best linear unbiased predictor) method. Body weight at
      first egg (BWF) is the only considered trait in this study. In total, 12 sires,
      31 dams and 77 daughters were involved in the EBV calculation. The results
      demonstrated that five microsatellite loci's polymorphism information content
      (PIC) ranged from 0.795 in locus AY493338 to 0.957 in locus AY493264 with average
      0.899; the parent-offspring relationships were built by these microsatellites'
      genotype, 12 families of half sibling and 2 families of full sibling were
      involved, and the relationship error is smaller than 10(-7). The EBV results
      suggest that the average EBV was significantly higher in females (average EBV is
      10.234 and 0.1045 for mother and daughter, respectively) than males (average EBV
      is just -26.44). The EBV results on BWF were in good agreement with the principle
      of GH (growth hormone) expression in poultry. These results show that paternity
      analyses of Chinese egg-laying ducks were basically resolved using the five
      microsatellite loci selected. The paternity relationships can apply in Chinese
      egg-laying duck breeding to quicken the improvement of genetic progress.

PMID- 19105045
TI  - Cloning and characterization of full-length coding sequence (CDS) of the ovine
      37/67-kDa laminin receptor (RPSA).
AB  - The 37-kDa Laminin Receptor Precursor (LRP)/67-kDa Laminin Receptor (LR), also
      known as ribosomal protein SA (RPSA), had been identified as a putative cell
      surface receptor for prions. Herein, we isolated the full-length coding sequence
      (CDS) of the ovine 37/67-kDa LRP/LR gene and submitted it to the GenBank under
      accession number EF649775. The open reading frame (ORF) of the 37/67-kDa LRP/LR
      CDS is 885 bp in length, containing six exons encoding a protein of 295 amino
      acids. The nucleotide sequence presented here is well coincided with the whole
      ovine genome of the 37/67-kDa LRP/LR previously published. Moreover, we
      identified four novel single nucleotide polymorphism sites (SNPs) at position 324
      in exon 4, positions at 809, 875, and 881 in exon 7, respectively. Further, based
      on the deduced amino acid sequence alignment of the 37/67-kDa LRP/LR from human,
      cattle, mice, pig, chicken, and sheep, we also identified three polymorphic amino
      acid sites (PAAs) at residues 241, 272, and a novel site at residue 270 in the
      putative indirect prion protein (PrP) interaction region (180-285) on 37/67-kDa
      LRP/LR. Prediction of protein secondary structure further indicated that PAAs at
      residues 241, 270 and 272 may cause protein conformation changes as predicted,
      which may affect on the binding with prion protein. In addition, multiple-tissues
      RT-PCR results revealed that 37/67-kDa LRP/LR mRNA is expressed in all the 11
      selected ovine tissues.

PMID- 19105046
TI  - Identification of differential gene expression for Kr1 gene in bread wheat using
      annealing control primer system.
AB  - Intergeneric hybridization is an important strategy to introgress alien genes
      into common wheat for its improvement. But presence of cross ability barrier
      mechanism regulated by Kr1 gene played a major destructive role for hybridization
      than other reported genes. In order to know the underlying molecular mechanism
      and to dissect out this barrier, a new annealing system, ACP (anneling control
      primer) system was used in chromosome 5B (containing Kr1 gene) specific
      Recombinant Inbred Line (RIL) population. Two differentially expressed fragments
      for Kr1 gene was identified, cloned and sequenced. Further the expression was
      confirmed by northern blotting analysis. Sequence analysis of the resulted clones
      revealed classes of putative genes, including stress responsive and signal
      transduction.

PMID- 19105047
TI  - Screening and identification of natural antisense transcripts in Helicobacter
      pylori by a novel approach based on RNase I protection assay.
AB  - Natural antisense transcripts (NATs) are endogenous RNA molecules that exhibit
      partial or complete complementarity to other RNAs. Studies have shown that NATs
      may participate in a broad range of gene regulatory events. The identification of
      NATs in human, mouse and Escherichia coli has revealed their widespread
      occurrence in both eukaryotic and prokaryotic life. However, little is known
      about NATs in Helicobacter pylori (H. pylori), a human pathogen which is
      associated with gastric diseases. Here we systematically screened NATs in H.
      pylori by a novel experimental strategy based on RNase I protection assay. We
      successfully constructed a cDNA library of NATs and developed a novel poly(A)
      tailed RT-PCR method to monitor the expression of NATs. After sequencing,
      bioinformatic analysis and expression detection, two novel NATs (NAT-39 and NAT
      67) were confirmed. They were, respectively, complementary to the following
      genes: iron-regulated outer membrane protein (frpB) and periplasmic iron-binding
      protein (ceuE). Taken together, the results suggest that NAT-39 and NAT-67 may
      participate in the regulation of iron homeostasis in H. Pylori in a sequence
      complementary manner with target mRNAs.

PMID- 19105048
TI  - The applications of PROs in clinical practice: what are they, do they work, and
      why?
AB  - BACKGROUND: Precisely defining the different applications of patient-reported
      outcome measures (PROs) in clinical practice can be difficult. This is because
      the intervention is complex and varies amongst different studies in terms of the
      type of PRO used, how the PRO is fed back, and to whom it is fed back. METHODS: A
      theory-driven approach is used to describe six different applications of PROs in
      clinical practice. The evidence for the impact of these applications on the
      process and outcomes of care are summarised. Possible explanations for the
      limited impact of PROs on patient management are then discussed and directions
      for future research are highlighted. RESULTS: The applications of PROs in
      clinical practice include screening tools, monitoring tools, as a method of
      promoting patient-centred care, as a decision aid, as a method of facilitating
      communication amongst multidisciplinary teams (MDTs), and as a means of
      monitoring the quality of patient care. Evidence from randomised controlled
      trials suggests that the use of PROs in clinical practice is valuable in
      improving the discussion and detection of HRQoL problems but has less of an
      impact on how clinicians manage patient problems or on subsequent patient
      outcomes. Many of the reasons for this may lie in the ways in which PROs fit (or
      do not fit) into the routine ways in which patients and clinicians communicate
      with each other, how clinicians make decisions, and how healthcare as a whole is
      organised. CONCLUSIONS: Future research needs to identify ways in with PROs can
      be better incorporated into the routine care of patients by combining qualitative
      and quantitative methods and adopting appropriate trial designs.

PMID- 19105049
TI  - Estimating health utilities in patients with asthma and COPD: evidence on the
      performance of EQ-5D and SF-6D.
AB  - OBJECTIVE: The objective of this study was to understand systematic differences
      in utility values derived from the EQ-5D and the SF-6D in two respiratory
      populations with heterogeneous disease severity. METHODS: This study involved
      secondary analysis of data from two cross-sectional surveys of patients with
      asthma (N = 228; Hungary) and COPD (N = 176; Sweden). Disease severity was
      defined according to GINA and GOLD guidelines for asthma and COPD, respectively.
      EQ-5D and SF-6D scores and their distributional characteristics were compared
      across the two samples by disease severity level. RESULTS: Within each patient
      population, mean EQ-5D and SF-6D scores were similar for the overall group and
      for those with moderate disease. Mean scores varied for patients with mild and
      severe disease. EQ-5D versus SF-6D scores in the asthma group by severity levels
      were 0.89 versus 0.80, 0.70 versus 0.73, 0.63 versus 0.64, and 0.51 versus 0.63,
      respectively. EQ-5D versus SF-6D scores in the COPD group by severity levels were
      0.85 versus 0.80, 0.73 versus 0.73, 0.74 versus 0.73, and 0.53 versus 0.62,
      respectively. CONCLUSIONS: Results suggest the EQ-5D and SF-6D do not yield
      consistent utility values in patients with asthma and COPD due to differences in
      underlying valuation techniques and the EQ-5D's limited response options relative
      to mild disease.

PMID- 19105050
TI  - Using Caenorhabditis elegans as a model organism for evaluating extracellular
      signal-regulated kinase docking domain inhibitors.
AB  - We have recently identified several novel ATP-independent inhibitors that target
      the extracellular signal-regulated kinase-2 (ERK2) protein and inhibit substrate
      phosphorylation. To further characterize these compounds, we describe the use of
      C. elegans as a model organism. C. elegans is recognized as a versatile and cost
      effective model for use in drug development. These studies take advantage of the
      well characterized process of vulva development and egg laying, which requires
      MPK-1, the homolog to human ERK2. It is shown that treatment of C. elegans eggs
      or larvae prior to vulva formation with a previously identified lead compound
      (76) caused up to 50% reduction in the number of eggs produced from the adult
      worm. In contrast, compound 76 had no effect on egg laying in young adult or
      adult worms with fully formed vulva. The reduction in egg laying by the test
      compound was not due to effects on C. elegans life span, general toxicity, or non
      specific stress. However, compound 76 did show selective inhibition of
      phosphorylation of LIN-1, a MPK-1 substrate essential for vulva precursor cell
      formation. Moreover, compound 76 inhibited cell fusion necessary for vulva
      maturation and reduced the multivulva phenotype in LET-60 (Ras) mutant worms that
      have constitutive activation of MPK-1. These findings support the use of C.
      elegans as a model organism to evaluate the selectivity and specificity of novel
      ERK targeted compounds.

PMID- 19105051
TI  - Preinduction of HSP70 promotes hypoxic tolerance and facilitates acclimatization
      to acute hypobaric hypoxia in mouse brain.
AB  - It has been shown that induction of HSP70 by administration of
      geranylgeranylacetone (GGA) leads to protection against ischemia/reperfusion
      injury. The present study was performed to determine the effect of GGA on the
      survival of mice and on brain damage under acute hypobaric hypoxia. The data
      showed that the mice injected with GGA survived significantly longer than control
      animals (survival time of 9.55 +/- 3.12 min, n = 16 vs. controls at 4.28 +/- 4.29
      min, n = 15, P < 0.005). Accordingly, the cellular necrosis or degeneration of
      the hippocampus and the cortex induced by sublethal hypoxia for 6 h could be
      attenuated by preinjection with GGA, especially in the CA2 and CA3 regions of the
      hippocampus. In addition, the activity of nitric oxide synthase (NOS) of the
      hippocampus and the cortex was increased after exposure to sublethal hypoxia for
      6 h but could be inhibited by the preinjection of GGA. Furthermore, the
      expression of HSP70 was significantly increased at 1 h after GGA injection. These
      results suggest that administration of GGA improved survival rate and prevented
      acute hypoxic damage to the brain and that the underlying mechanism involved
      induction of HSP70 and inhibition of NOS activity.

PMID- 19105052
TI  - The role of switching, inhibition and working memory in older adults' performance
      in the Wisconsin Card Sorting Test.
AB  - The Wisconsin Card Sorting Test (WCST) is considered a typical executive test.
      However, several interesting questions are still open as to the specific
      executive processes underlying this task. In the present study, we explored how
      local and global switching, inhibition and working memory, assessed through the
      Number-Letter, the Stop Signal and the Reading Span tasks, relate to older
      adults' performance in the WCST. Results showed that older adults' performance
      variability in the number of perseverative errors was predicted by the local
      switch component of the Number-Letter task. Results also showed age-related
      differences in inhibition, working memory and global switching, while local
      switching resulted largely spared in aging. This study provides evidence that
      switching abilities may contribute to performance of older adults in the WCST. It
      also provides initial evidence suggesting that switching processes, associated
      with local switch costs, are involved in performance on the WCST, at least in
      older adults.

PMID- 19105053
TI  - Perception of temporal order: the effects of age, sex, and cognitive factors.
AB  - The present paper investigates the effects of age, sex, and cognitive factors on
      temporal-order perception. Nine temporal-order tasks were employed using two and
      four stimuli presented in the auditory and visual modalities. Significantly
      increased temporal-order thresholds (TOT) in the elderly were found for almost
      all tasks, while sex differences were only observed for two tasks. Multiple
      regression analyses show that the performance on most temporal-order tasks can be
      predicted by cognitive factors, such as speed of fluid reasoning, short-term
      memory, and attention. However, age was a significant predictor of TOT in three
      tasks using visual stimuli. We conclude (1) that age-related differences can
      often be attributed to cognitive factors involved in temporal-order perception,
      and (2) that the concept of temporal-order perception is more complex than
      implied by the current models.

PMID- 19105054
TI  - Rapid automatized naming and learning disabilities: does RAN have a specific
      connection to reading or not?
AB  - This work is an extension of a study by Waber, Wolff, Forbes, and Weiler (2000 )
      in which the specificity of naming speed deficits to reading disability (RD) was
      examined. One hundred ninety-three children (ages 8 to 11) evaluated for learning
      disabilities were studied. It was determined how well rapid automatized naming
      (RAN) discriminated between different diagnostic groups (learning impaired [LI]
      with and without RD) from controls and from each other. Whereas Waber et al.
      concluded that RAN was an excellent tool for detecting risk for learning
      disabilities in general, the results of the present study point to a more
      specific connection between RAN and RD.

PMID- 19105055
TI  - Factors contributing to increased serum urate in postmenopausal Japanese females.
AB  - OBJECTIVE: The level of serum urate is generally elevated in postmenopausal
      individuals. In addition to estrogen, other menopause-related factors may also
      affect uric acid metabolism in postmenopausal females. Accordingly, we
      investigated factors related to increased serum urate levels in addition to lack
      of estrogen. SUBJECTS AND METHODS: We studied 448 females who participated in an
      annual health check-up. None were being treated for gout, hyperuricemia, or
      diabetes mellitus, and no subjects had a history of hysterectomy and had never
      used estrogens or progestins. Body mass index (BMI), homeostasis model of insulin
      resistance (HOMA-R), and ethanol ingestion were investigated in all subjects,
      while information regarding menopause status was also obtained. RESULTS: Serum
      urate levels rose from the age of 46 to 60 years in the subjects. Multivariate
      regression analysis showed that BMI, HOMA-R, ethanol ingestion and menopause were
      independently associated with serum urate level. In addition, BMI and HOMA-R were
      higher in postmenopausal, as compared to premenopausal, subjects. CONCLUSION: Our
      results suggest that menopause-related insulin resistance, obesity and ethanol
      ingestion as well as menopause may contribute to an increase in level of serum
      urate in postmenopausal Japanese women.

PMID- 19105056
TI  - Functional neuroimaging of grammatical class: ambiguous and unambiguous nouns and
      verbs.
AB  - Neuropsychological and neuroimaging studies of grammatical-class differences
      suggest that nouns and verbs may be associated with different brain regions. The
      current functional magnetic resonance imaging (fMRI) study focused on auditory
      grammaticality judgements of two-word stimuli consisting of noun/verb ambiguous
      and unambiguous nouns and verbs preceded by either "the" or "to". The fMRI
      results showed effects of class ambiguity in the left inferior frontal gyrus,
      possibly due to greater selection demands, and effects of grammaticality ("yes"
      vs. "no" response) in left superior temporal gyrus, consistent with greater
      activation for trials with greater conflict. In addition, posterior left temporal
      lobe regions showed increased activity on unambiguous trials for verbs than for
      nouns, consistent with prior imaging studies. Thus, in a task specifically
      focused on the grammatical (rather than semantic) aspects of words and that used
      morphologically simple nouns and verbs controlled for imageability, verbs
      preferentially activated posterior temporal but not frontal lobe regions.
      However, for ambiguous trials in this same region, nouns showed greater
      activation than verbs, suggesting that these effects can be modulated by class
      ambiguity.

PMID- 19105057
TI  - The persistence of stuttering behaviours in older people.
AB  - OBJECTIVE: To measure and describe the speech characteristics of a group of 16
      people over the age of 55 years who self-reported stuttering into adulthood.
      DESIGN: A cross-sectional, descriptive design was used. SUBJECTS: Sixteen
      participants were divided into two groups: a group of 12, (mean age 68.8) who
      self-reported that they continued to stutter in older age, and a group of four
      who self-reported recovery from stuttering in adulthood (mean age 75.5). METHODS:
      Speech samples during face-to-face and telephone conversations were analysed for
      stuttering frequency (%SS) and stuttering behaviours using the Lidcombe
      Behavioural Data Language. RESULTS: Descriptive statistics showed that all
      participants in the persistent stuttering group evidenced stuttering with varying
      severity. In the group of four who reported recovery, one participant presented
      with measurable stuttering behaviours in the conversational and telephone sample.
      Participants, in the group who reported persistence of stuttering evidenced the
      full range of stuttering behaviours seen in younger adults. CONCLUSION:
      Stuttering is a disorder that may persist for some beyond 55 years of age. This
      result compels investigation to explore how stuttering impacts on activity and
      participation for this older group.

PMID- 19105058
TI  - A controlled evaluation of web-based training for teachers and public health
      practitioners on the prevention of eating disorders.
AB  - The effectiveness of a web-based prevention program designed for elementary
      school teachers was examined in 78 elementary school teachers and 89 local public
      health practitioners (who provide support to schools). Participants were assigned
      to either the intervention (n = 95) or comparison (n = 72) study groups. All
      participants completed self-report online measures prior to, and following, the
      60-day study period assessing knowledge about various factors that influence body
      image in children and efficacy to fight weight bias in the school. Information
      was also solicited on the feasibility of, and on the perceived benefit of the web
      based program as a knowledge translation tool, in terms of layout and content.
      The Student Body program was found to be successful in improving knowledge
      concerning facts about dieting among the teacher participants, and in increasing
      efficacy to fight weight bias among the public health participants. Overall, the
      feedback was very positive concerning the layout and content of the Student Body.
      Participants reported an overall improvement in their awareness about how weight
      bias can be present in their teaching practices, and how this can trigger body
      image concerns among their students. Findings have implications for using the web
      to engage teachers in the prevention of disordered eating among school age
      children.

PMID- 19105059
TI  - Treating patients with eating disorders: an examination of treatment providers'
      experiences.
AB  - Patients with eating disorders bring unique challenges to treatment providers.
      The purpose of this study was to explore treatment providers' experiences working
      with patients with eating disorders. Specifically, we investigated 1) the
      frequency and management of commentary about the treatment providers' appearance
      from patients, 2) personal changes in affect, vigilance around appearance, and
      eating behaviors in treatment providers, and 3) feedback and suggestions about
      effectively working with these patients. Using quantitative and qualitative
      methods, 43 professional eating disorder treatment providers attending the
      Multiservice Eating Disorder Association (MEDA) annual conference completed a
      questionnaire created for this study. Results suggest that most treatment
      providers experienced direct and indirect commentary about their appearance from
      patients and experienced notable changes in their view of food, eating behaviors,
      and vigilance of their own and others' appearance while working with these
      patients. Recommendations and suggestions from treatment providers about
      effectively treating these patients and managing personal changes are explored.

PMID- 19105060
TI  - Effects of dietary restraint and body mass index on the relative reinforcing
      value of snack food.
AB  - The present study examined the independent and interactive association between
      dietary restraint, body mass index (BMI) and the relative reinforcing value of
      food. Four hundred and three introductory psychology students completed
      questionnaires assessing age, gender, BMI, hunger, smoking status, nicotine
      dependence, dietary restraint, hedonic ratings for snack food and fruits and
      vegetables and the relative reinforcing value of snack food and fruits and
      vegetables. In the overall sample, results indicated a dietary restraint x BMI
      interaction after controlling for age, hunger, nicotine dependence, and hedonics.
      However, when regression models were separated by gender, the BMI x restraint
      interaction emerged only for females and not for males. Findings suggest that BMI
      moderates the relationship between dietary restraint and snack food reinforcement
      in females only, such that restraint and snack food reinforcement are inversely
      correlated in females with lower BMI, but restraint is positively correlated with
      snack food reinforcement in females with higher BMI. Theoretical and clinical
      implications of these findings are discussed.

PMID- 19105061
TI  - Is there a relationship between parental self-reported psychopathology and
      symptom severity in adolescents with anorexia nervosa?
AB  - The current study aimed to screen for indications of psychopathology displayed by
      the parents of adolescents diagnosed with Anorexia Nervosa (AN), and examine the
      relationship between severity of adolescent eating disorder symptoms and parental
      psychopathology. Sixty female adolescents diagnosed with DSM-IV-TR AN
      (restricting-type and binge-purge-type) were administered the Eating Disorder
      Examination (EDE) and parents completed the Symptom Checklist 90-Revised (SCL-90
      R). As compared to established non-patient norms, both fathers and mothers of
      adolescents with AN reported greater levels of obsessive compulsive behaviors,
      hostility, depression, and anxiety as measured by the SCL-90-R. In addition,
      duration of AN was positively associated with hostility scores in fathers, and
      global EDE scores were associated with hostility in mothers. While parental
      scores on the SCL-90 were elevated as compared to community samples, results of
      this study do not support a direct influence of parental psychopathology on
      symptom severity of adolescent AN. Increasing rates of hostility scores in
      parents with increased duration of AN may represent either a response to the
      presence of the disorder or be a maintaining factor for AN.

PMID- 19105062
TI  - A pilot study of a family-based treatment for adolescent anorexia nervosa: 18-
      and 36-month follow-ups.
AB  - The current study evaluated the outcome of family-based treatment for female
      adolescents with anorexia nervosa (N = 32), at the Anorexia-Bulimia Outpatient
      Unit in Goteborg, Sweden. Patients/parents were assessed pre-treatment, at 18-
      and 36-month follow-ups concerning eating disorder symptoms, general
      psychopathology, family climate and BMI. At the 36-month follow-up, 75% of the
      patients were in full remission with reduction in eating disorder symptoms and
      internalizing problems and they experienced a less distant and chaotic atmosphere
      in their families. These results show that family-based treatment appears to be
      effective in adolescent anorexia nervosa patients regarding areas examined in
      this study.

PMID- 19105066
TI  - The last word on the 29th Olympiad: redundant, revealing, remarkable, and
      redundant.

PMID- 19105063
TI  - Binge eating: neurochemical insights from animal models.

PMID- 19105067
TI  - Parent and self-ratings of executive function in adolescents with specific
      language impairment.
AB  - BACKGROUND: There is accumulating evidence that adolescents with specific
      language impairment (SLI) have impairments in domains beyond formal language that
      may affect academic and social outcomes. The findings of previous studies as well
      as parent reports of behavioural concerns suggest that they lag behind peers in
      functions such as self-regulation of verbal behaviour and strategic language use
      suggesting that executive function may be a potential domain worthy of study in
      adolescents with SLI. The evaluation of executive functions in daily living could
      provide critical information for intervention for adolescents with SLI, and also
      inform studies of the relationship between language and executive functioning in
      a developing system. AIMS: To compare ratings of executive function in
      adolescents with specific language impairment to those of their parents and
      typically developing peers. METHODS & PROCEDURES: This study examined parent and
      self-ratings of executive function in adolescents with SLI and typically
      developing peers. Twenty-one adolescents with SLI and 21 age- and gender-matched
      peers (age range = 11-18 years) rated their executive functions in daily living
      using the Behavior Rating Inventory of Executive Function - Self-Report Form
      (BRIEF-SR), and their parents provided companion ratings. OUTCOMES & RESULTS:
      Adolescents in both groups rated themselves more positively than did their
      parents, and the presence of language impairment was associated with more
      negative ratings by both parents and adolescents. Fifty-seven per cent of the
      parents of adolescents with SLI rated their child's executive function abilities
      as being in the clinically impaired range, compared with 10% in the typically
      developing group. CONCLUSIONS & IMPLICATIONS: The results of this study suggest
      that many adolescents with SLI have perceived impairments in executive functions
      that affect their performance in daily living. What remains to be determined is
      whether language and executive function impairments are co-morbid conditions or
      causally linked. Few assessment tools address the unique characteristics of
      adolescent clinical populations, including those with SLI. These findings suggest
      that self- and parent ratings of executive function may offer useful information
      for treatment planning. A greater understanding of the relation of executive
      functions to language has important implications for the timing and content of
      therapeutic intervention.

PMID- 19105068
TI  - Home literacy environment: characteristics of children with cerebral palsy.
AB  - BACKGROUND: Various aspects of the home literacy environment are considered to
      stimulate the emergent literacy development in children without disabilities. It
      is important to gain insight into the home literacy environment of children with
      cerebral palsy given that they have been shown to have difficulty acquiring
      literacy skills. AIMS: The aims of the present study were to investigate whether
      the home literacy environment of children with cerebral palsy was comparable with
      that of peers without disabilities and to investigate to what extent speech, fine
      motor, and intellectual impairments limit their home literacy experiences.
      METHODS & PROCEDURES: Questionnaires addressed to the parents of the children
      were devised to investigate differences in the home literacy environment in 40
      children with cerebral palsy and in 62 peers without disabilities who were
      comparable on chronological age, i.e., 6 years old, socio-economic status (SES)
      and sex. The relative influence of speech intelligibility, fine motor skills, and
      intelligence skills for the home literacy environment factors of children with
      cerebral palsy was investigated. OUTCOMES & RESULTS: Only a few group differences
      were significant: children with cerebral palsy were less interested in
      participating in writing activities, and less involved in word-orientation
      activities during shared storybook reading. On the other hand, parents of
      children with cerebral palsy were doing more leisure activities with their child.
      The speech intelligibility scores of the children with cerebral palsy predicted
      the amount of emergent literacy activities they were doing with their parents, as
      wells as their active participation in word-related activities during storybook
      reading. In addition, the active participation of the child in story-related
      activities could be predicted by his or her fine motor skills. Furthermore,
      parents of the children in the comparison group often had high expectations,
      while parents of the children with cerebral palsy often did not know what
      expectations to have for their child's literacy level at the end of elementary
      school. CONCLUSIONS & IMPLICATIONS: Although both groups have stimulating home
      literacy environments, children with cerebral palsy with speech or fine motor
      impairments are disadvantaged in a small number of literacy activities. Teachers
      and speech and language therapists can work with parents to give them suggestions
      on how to conduct emergent literacy activities with their child with speech
      impairments as well as how on to involve their child with speech and fine motor
      dysfunctions more actively in storybook reading activities. Furthermore, parents
      should be given more information about their child's language development in
      order the better to understand what goals are achievable so they may begin to
      form realistic expectations.

PMID- 19105069
TI  - Reading and spelling in children with severe speech and physical impairments: a
      comparative study.
AB  - BACKGROUND: Effective literacy skills are crucial in supporting communication for
      children with severe speech and physical impairments (SSPI). Reading and spelling
      difficulties are reported to be over-represented in this group, even where
      language and cognitive skills are age appropriate. AIMS: To compare the
      performance of children with SSPI on a range of language, reading and spelling
      tasks with that of their typically developing peers matched for receptive
      vocabulary and mental age. METHODS & PROCEDURES: A wide range of tasks was
      developed as part of a larger study exploring phonological awareness, reading and
      spelling skills. All tasks were accessible to children with severe physical
      impairments. Two groups of primary school-aged children were recruited, children
      with SSPI of average intelligence, and naturally speaking peers, matched for
      receptive vocabulary. Children were assessed individually on language, non-verbal
      cognition, phonological awareness, reading and spelling tasks. OUTCOMES &
      RESULTS: Sixteen children with SSPI were recruited. Their performance was
      compared with that of 15 naturally speaking peers, matched for receptive
      vocabulary scores. The children with SSPI achieved significantly lower scores on
      reading and spelling measures relative to their naturally speaking peers.
      However, at least one participant with SSPI scored at ceiling on each task,
      indicating that SSPI do not preclude the development of reading and spelling, at
      least in the early stages of literacy development. CONCLUSIONS & IMPLICATIONS:
      This study indicates that some children with severe speech impairments can
      develop phonological awareness, reading and spelling skills. However, the data
      suggest that phonological awareness may not be as good a predictor of reading and
      spelling abilities in this group of children as in typically developing children.
      Further research is needed to track development of reading and spelling, as well
      as the instructional support needed to scaffold more effective skills in these
      areas.

PMID- 19105070
TI  - Communicative gestures and vocabulary development in 36-month-old children with
      Down's syndrome.
AB  - BACKGROUND: Children with Down's syndrome seem to show a preference for the use
      of gestural rather than vocal productions during the first stages of language
      development. This 'gestural advantage' could actually be due to a developmental
      strategy used to compensate the difficulties in verbal production that are
      typical of language development in this population. AIMS: The principal aim of
      the present study is to analyse the relationships between gesture production and
      vocabulary development in children with Down's syndrome, verifying the existence
      of any similarities with the processes that characterize typical development.
      METHODS & PROCEDURES: Twenty 36-month-old Italian children with Down's syndrome
      participated in the study. Each child's spontaneous gestural and vocal production
      was assessed during a mother-and-child play session. Their psychomotor
      development was evaluated using the Brunet-Lezine Scale of Infant Development;
      and their vocabulary size, with regards both production and comprehension, was
      assessed using the Italian version of the MacArthur Communicative Development
      Inventory (CDI). Following a longitudinal perspective, parents were requested to
      complete the inventory at 6 months after the first evaluation (i.e., at 42
      months). Data analyses focused both on the concurrent relations of gesture
      production, vocabulary size and psychomotor development, and on the longitudinal
      relations between gesture production and subsequent vocabulary development.
      OUTCOMES & RESULTS: As regards concurrent relationships, gesture production
      appeared to be related both to psychomotor development and to word comprehension,
      but not to word production. Nevertheless, as regards longitudinal relationships,
      gesture production at 36 months was significantly correlated to the subsequent
      vocabulary production, assessed at 42 months using the MacArthur Communicative
      Development Inventory (CDI), though this relationship appeared to be mediated by
      word comprehension. CONCLUSIONS & IMPLICATIONS: Two processes in the gesture
      production of children with Down's syndrome appear to be similar to those
      previously identified in typically developing children: (1) the role of gestures
      as a 'bridge' between word comprehension and word production; and (2) the
      predictive role of gestures, in association with comprehension, on vocabulary
      development.

PMID- 19105071
TI  - Children with phonological problems: a survey of clinical practice.

PMID- 19105072
TI  - Accuracy of parent identification of stuttering occurrence.
AB  - BACKGROUND: Clinicians rely on parents to provide information regarding the onset
      and development of stuttering in their own children. The accuracy and reliability
      of their judgments of stuttering is therefore important and is not well
      researched. AIM: To investigate the accuracy of parent judgements of stuttering
      in their own children's speech when compared with judgements made by the parents
      of normally fluent children and experienced clinicians. METHODS & PROCEDURES:
      Twenty parents of children who stutter made judgements of stuttering during
      repeated presentations of 3-min audio-visual samples of their children. Twenty
      control parents of children (age and gender matched) who do not stutter also
      assessed the children who stutter speech samples. OUTCOMES & RESULTS: The parents
      of both the children who stutter and those who do not stutter displayed high
      levels of judgement accuracy (parents, of children who stutter percentage
      agreement mean (standard deviation) = 90.9 (6.02); parents of children who do not
      stutter = 86.4 (9.7)) and consistency (90.3-90.6%) in judging stuttering in young
      children. But the parents of children who stutter showed significantly higher
      levels of accuracy (t(59) = 4.63, p<0.0001; d = 0.8) in judging stuttered
      intervals than the children who do not stutter parents. CONCLUSIONS &
      IMPLICATIONS: Parents of children who stutter may be both accurate and reliable
      in identifying brief intervals of speech containing stuttering and non-stuttering
      in their own children.

PMID- 19105073
TI  - Spatiotemporal and frequency signatures of noun and verb processing: a wavelet
      based beamformer study.
AB  - A total of 8 participants were tested using magnetoencephalography for
      investigating the spatial, temporal, and frequency signatures of noun and verb
      processing in the brain. Visually presented nouns and verbs both activated the
      occipital, left posterior temporal, and left inferior frontal cortices at a
      latency range of 106-329 ms in a frequency range of 24-98 Hz. Nouns activated the
      left posterior temporal area while verbs activated the inferior left frontal area
      at a latency range of 411-430 ms in a frequency range of 116-137 Hz. Nouns and
      verbs were processed in similar brain areas during early latency and relatively
      low frequency, but were processed in different brain areas during late latency
      and high frequency. The results indicate that there are distinct neural
      substrates underlying different aspects of the language system. This finding
      sheds light on the cerebral mechanisms of impairments of selective word
      categories in patients with brain damage in clinical neuropsychology.

PMID- 19105074
TI  - The Hatfield Image Test (HIT): a new picture test and norms for experimental and
      clinical use.
AB  - We present a new corpus of 147 high-quality photographic colour images (the
      Hatfield Image Test: HIT). Existing sets of pictorial stimuli tend to be line
      drawn, contain many items that are readily identifiable by healthy participants,
      and, therefore, have an inherent tendency towards ceiling effects in the normal
      population. The broad range of item difficulty and range of semantic
      subcategories in the HIT permits researchers to select stimuli of appropriate
      difficulty as required. We present naming data from 152 healthy participants.
      Additionally, we present mean ratings for each item on several widely used
      psycholinguistic variables: age of acquisition, colour diagnosticity,
      familiarity, name agreement (and the H statistic), visual complexity, and word
      frequency. These stimuli provide a useful corpus for experimental and clinical
      researchers.

PMID- 19105075
TI  - The effects of pregnancy on memory: recall is worse but recognition is not.
AB  - Women who are pregnant frequently complain of memory problems. Past research
      suggests that pregnancy is associated with a measurable decline when memory is
      tested using free recall but not when memory is tested using recognition.
      However, no prior studies on recognition memory tested performance across two
      time periods (e.g., pregnant vs. postpartum). A repeated measures design has
      greater power than a between-subject design to detect any difference in
      recognition memory performance that might exist. We administered a standardized
      memory test to 37 women during pregnancy and then again during the postpartum
      period 3 to 12 months later. Our results show that during pregnancy free-recall
      performance was somewhat worse (in agreement with prior research) than postpartum
      but that recognition performance was not worse and was, if anything, slightly
      enhanced. These results weigh against a purely biological explanation of the
      memory difficulties associated with pregnancy and instead point to a strategic
      explanation. In particular, the results suggest that when women are pregnant they
      rely more on item-specific processing (which can enhance recognition) but when
      they are no longer pregnant they rely more on relational processing (which
      enhances recall).

PMID- 19105077
TI  - Cognitive-affective correlates and predictors of superficial dyspareunia.
AB  - This study investigated the role of cognitive-affective variables related to
      sexuality, chronic pain, individual and relational well-being in superficial
      dyspareunia. Although symptomatic women (n = 80) differed from complaint-free
      controls (n = 62) on all variables, sexuality related measures had the most
      important contribution into the prediction of group membership. Dyspareunia
      subgroups based on the presence/absence of a concomitant diagnosis of provoked
      vestibulodynia were only distinguishable on pain intensity but not on variables
      related to sexuality and psychological well-being. The present findings
      underscore the relevance of psychosexual factors in women with superficial
      dyspareunia.

PMID- 19105078
TI  - Sexual pleasure and motivation.
AB  - Individuals engage in behaviors or partake of specific substances because it
      pleases them. Indeed, without the sensations of pleasure and displeasure we would
      be unlikely to repeat or restrict behaviors. Since repetitive sexual activity
      over the millennia has ensured the continuance of the human race, it is perhaps
      surprising that pleasure has received little attention in the research literature
      on sexual function and behavior. By exploring sexual pleasure and motivation
      theories and studies relevant to the evaluation of sexual function and
      dysfunction, a goal response model is presented. This model proposes a route from
      sexual stimuli, via cognitive and emotional processing to behavior and subsequent
      feedback, which illustrates how eudemonic goals could influence treatment
      outcomes.

PMID- 19105079
TI  - Meanings and political implications of "psychopathology" in a gender identity
      clinic: a report of 10 cases.
AB  - Beginning in August 2007, we committed ourselves to a clinical review the co
      morbid diagnostic patterns of the last 10 patients interviewed by our Gender
      Identity Clinic. We found 90% of these diverse patients had at least one other
      significant form of psychopathology. This finding seems to be in marked contrast
      to the public, forensic, and professional rhetoric of many who care for
      transgendered adults. Much of this rhetoric sounds remarkably certain about the
      long-term value of gender transition, hormones, and sex reassignment surgery in
      improving the lives of those with Gender Identity Disorder (GID). Such clinical
      certainty would have to be based on carefully established sophisticated follow-up
      findings. These are lacking. The psychopathologies in this series included
      problems of mood and anxiety regulation and adapting in the world. Two of the 10
      have had persistent significant regrets about their previous transitions. In
      discussing management decisions, civil rights, and ethics, we planned to
      separately briefly present the 10 patients. However, our decision to seek
      patients' permission proved so upsetting to three of the first six patients that
      we altered the structure of this report. Our attempt to follow the ethical
      principle of informed consent caused us to violate the principle of
      nonmalfiescence. This distressing experience only illustrates, however, the
      disadvantage of discussing professional concepts with lay audiences. Emphasis on
      civil rights is not a substitute for the recognition and treatment of associated
      psychopathology. Gender identity specialists, unlike the media, need to be
      concerned about the majority of patients, not just the ones who are apparently
      functioning well in transition.

PMID- 19105080
TI  - Assessment, treatment, and relapse prevention: male hypoactive sexual desire
      disorder.
AB  - There is a dearth of conceptual, clinical, and empirical work in the area of male
      hypoactive sexual desire disorder. Instead, the sexual medicine approach has
      focused on erectile dysfunction and premature ejaculation. This
      conceptual/clinical article focuses on a couple, integrative, psychobiosocial
      approach to understand, assess, treat, and relapse prevention of this very
      important problem. The hope is to generate conceptual, clinical, and research
      interest in this largely ignored dysfunction.

PMID- 19105081
TI  - Marital satisfaction, sexual problems, and the possible difficulties on sex
      therapy in traditional Islamic culture.
AB  - We plan to investigate the level of marital satisfaction, the prevalence of
      sexual problems, and related issues in couples who were referred to an outpatient
      clinic of psychiatry for their sexual problems. All were living according to
      traditional Islamic culture. Twenty-five (80.64%) of the couples attended the
      clinic for not being able to have any sexual intercourse. Overall, 25.8% of the
      women, and 3.2% of the men had been married without their consent; those
      marriages were arranged and mediated by matchmakers. Vaginismus (58.06%) was the
      most common diagnosis among women and premature ejaculation (38.70%) among men.
      We found that marital satisfaction was affected by the mode of marriage.

PMID- 19105085
TI  - Exploring self-defining memories in schizophrenia.
AB  - Previous studies have shown that patients with schizophrenia are impaired in
      recalling specific events from their personal past. However, the relationship
      between autobiographical memory impairments and disturbance of the sense of
      identity in schizophrenia has not been investigated in detail. In this study the
      authors investigated schizophrenic patients' ability to recall self-defining
      memories; that is, memories that play an important role in building and
      maintaining the self-concept. Results showed that patients recalled as many
      specific self-defining memories as healthy participants. However, patients with
      schizophrenia exhibited an abnormal reminiscence bump and reported different
      types of thematic content (i.e., they recalled less memories about past
      achievements and more memories regarding hospitalisation and stigmatisation of
      illness). Furthermore, the findings suggest that impairments in extracting
      meaning from personal memories could represent a core disturbance of
      autobiographical memory in patients with schizophrenia.

PMID- 19105086
TI  - Expertise promotes facilitation on a collaborative memory task.
AB  - The effect of expertise on collaborative memory was examined by comparing expert
      pilots, novice pilots, and non-pilots. Participants were presented with aviation
      scenarios and asked to recall the scenarios alone or in collaboration with a
      fellow participant of the same expertise level. Performance in the collaborative
      condition was compared to nominal group conditions (i.e., pooled individual
      performance). Results suggest that expertise differentially impacts collaborative
      memory performance. Non-experts (non-pilots and novices) were relatively
      disrupted by collaboration, while experts showed a benefit of collaboration.
      Verbal protocol analyses identified mechanisms related to collaborative skill and
      domain knowledge that may underlie experts' collaborative success. Specifically,
      experts were more likely than non-experts to explicitly acknowledge partner
      contributions by repeating back previously made statements, as well as to further
      elaborate on concepts in those contributions. The findings are interpreted
      according to the retrieval strategy disruption theory of collaborative memory and
      theories of grounding in communication.

PMID- 19105087
TI  - The normative and the personal life: individual differences in life scripts and
      life story events among USA and Danish undergraduates.
AB  - Life scripts are culturally shared expectations about the order and timing of
      life events in a prototypical life course. American and Danish undergraduates
      produced life story events and life scripts by listing the seven most important
      events in their own lives and in the lives of hypothetical people living ordinary
      lives. They also rated their events on several scales and completed measures of
      depression, PTSD symptoms, and centrality of a negative event to their lives. The
      Danish life script replicated earlier work; the American life script showed minor
      differences from the Danish life script, apparently reflecting genuine
      differences in shared events as well as less homogeneity in the American sample.
      Both consisted of mostly positive events that came disproportionately from ages
      15 to 30. Valence of life story events correlated with life script valence,
      depression, PTSD symptoms, and identity. In the Danish undergraduates, measures
      of life story deviation from the life script correlated with measures of
      depression and PTSD symptoms.

PMID- 19105088
TI  - Inhibitory control of memory in normal ageing: dissociation between impaired
      intentional and preserved unintentional processes.
AB  - The aim of this study was to compare the performance of elderly and young
      participants on a series of memory tasks involving either intentional or
      unintentional inhibitory control of memory content. Intentional inhibition
      processes in working and episodic memory were explored with directed forgetting
      tasks and in semantic memory with the Hayling task. Unintentional inhibitory
      processes in working memory, long-term memory, and semantic memory were explored
      with an interference resolution task, the retrieval practice paradigm, and the
      flanker task, respectively. The results indicate that elderly participants'
      performance on the two directed forgetting tasks and the Hayling task is lower
      than that of young ones, and that this impairment is not related to their initial
      memory capacity. This suggests that there is a specific dysfunction affecting
      intentional inhibitory control of memory contents in normal ageing.

PMID- 19105089
TI  - Motivation for weight loss affects recall from autobiographical memory in
      dieters.
AB  - Two studies examined the connection between motivation for weight loss and
      autobiographical memory by comparing characteristics of autobiographical memories
      between dieters and non-dieters. Study 1 involved 29 normal/overweight dieters
      and 48 non-dieters, and Study 2 involved 18 obese dieters and 18 normal weight
      non-dieters. Memories recalled in response to dieting-related cue words were
      rated as more central to the person's identity and life story and contained more
      body- or weight-related elements for the dieters than the non-dieters. No
      differences between dieters and non-dieters were found on memories recalled in
      response to neutral cue words. The findings are discussed in relation to the
      notions of the working self (Conway & Pleydell-Pearce, 2000) and current concerns
      (Klinger, 1978).

PMID- 19105090
TI  - Serial position effects in 2-alternative forced choice recognition: functional
      equivalence across visual and auditory modalities.
AB  - Two experiments examined Ward, Avons, and Melling's (2005) proposition that the
      serial position function is task, rather than modality, dependent. Specifically,
      they proposed that for backward testing the 2-alternative forced-choice (2AFC)
      recognition paradigm is characterised by single-item recency irrespective of the
      modality of the stimulus presentation. In Experiment 1 the same nonword
      sequences, presented both visually or auditorily, produced qualitatively
      equivalent serial position functions with 2AFC testing. Forward testing produced
      a flat serial position function, while backward testing produced two-item recency
      in the absence of primacy. In order to rule out the possibility that the serial
      position functions for visual stimuli were the product of sub-vocal rehearsal,
      Experiment 2 employed articulatory suppression during the presentation phase.
      Serial position function equivalence was again observed together with a modest
      impairment in overall recognition rates. Taken together, these data are
      consistent with the Ward et al. proposition and further support the existence of
      a visual memory that can facilitate storage of visual-verbal material (e.g.
      Logie, Della Sella, Wynn, & Baddeley, 2000). However, the observation of two-item
      recency contradicts the original duplex account of single-item recency
      traditionally observed for backwards recognition testing of visual stimuli
      (Phillips & Christie, 1977).

PMID- 19105091
TI  - Pregnancy outcome of patients following deep venous thrombosis.
AB  - OBJECTIVE: To investigate pregnancy outcome of patients with a history of deep
      vein thrombosis (DVT). METHODS: A population-based study comparing all
      pregnancies of patients with and without a history of DVT was conducted.
      Deliveries occurred during the years 1988-2007 at a tertiary Medical Center.
      Stratified analyses were performed using multivariable logistic regression models
      and the Mantel-Haenszel technique. RESULTS: During the study there were 212,086
      deliveries, of which 122 (0.06%) occurred in patients with a history of DVT.
      Using a multivariate analysis, with backward elimination, the following
      conditions were significantly associated with DVT: advanced maternal age (OR,
      1.1; 95% CI, 1.02-1.1; p = 0.004), chronic hypertension (OR, 2.9; 95% CI, 1.4
      6.0; p = 0.005) and previous caesarean delivery (OR, 2.8; 95% CI, 1.9-4.1; p <
      0.001). Patients with a history of DVT were more likely to have caesarean
      deliveries (OR, 2.6; 95% CI, 1.8-3.8; p < 0.001) than non-DVT patients. After
      controlling for possible confounders, such as maternal age, hypertensive
      disorders, pregestational diabetes and multiple gestations, by using another
      multivariate analysis with preterm delivery (<37 weeks' gestation) as the outcome
      variable, DVT was found to be an independent risk factor for preterm birth (OR,
      1.8; 95% CI, 1.1-2.9; p = 0.033). This association remained significant after
      controlling for labor induction, using the Mantel-Haenszel technique (OR, 1.8;
      95% CI, 1.1-3.0; p = 0.011). No significant differences were noted between the
      groups regarding perinatal outcomes such as low Apgar scores, congenital
      malformations or perinatal mortality. CONCLUSIONS: A history of DVT is an
      independent risk factor for spontaneous preterm delivery. Nevertheless, in our
      population it is not associated with adverse perinatal outcome.

PMID- 19105092
TI  - Left ventricular performance and exercise capacity in patients aged 65 years and
      older treated by primary coronary angioplasty or conservatively for acute
      myocardial infarction--a one-year follow-up.
AB  - BACKGROUND: Elderly patients hospitalised for congestive heart failure (CHF) due
      to myocardial infarction (MI) have very poor prognosis, particularly if CHF
      symptoms are caused by left ventricular (LV) systolic dysfunction. Early invasive
      strategy is considered the best method of preventing post-MI LV dysfunction. The
      clinical impact of early invasive strategy on prognosis in elderly patients with
      acute MI has yet to be completely defined because of the poor enrolment of
      elderly patients in large randomised trials. AIM: To asses whether treatment of
      acute MI in patients aged >65 years using percutaneous coronary intervention
      (PCI) results in significantly better long-term cardiovascular performance in
      comparison with conservative treatment (CT). METHODS: Our study involved 90 MI
      patients who underwent diagnostic spiroergometry: 40 patients (mean age 73 years)
      treated conservatively and 50 (mean age 71 years) by PCI. Echocardiographic
      examinations and spiroergometric tests were performed at 3-, 6- and 12-month
      follow-up. Plasma NT-proBNP levels were measured on admission and at 6- and 12
      month follow-up. RESULTS: Echocardiographic and spiroergometric parameters were
      significantly better in PCI patients in each of the analysed periods and showed
      significant improvement throughout follow-up (the largest between months 3 and
      6). In the CT patients these parameters showed significant improvement only
      between months 3 and 6. After one year, studied parameters were better in PCI
      patients (LVESD: 3.1+/-0.4 vs. 3.5+/-0.6 cm; p <0.001, LVEF: 62.8+/-6.6 vs.
      55.8+/-8.3%; p <0.001, LVEDD: 4.9+/-0.4 vs. 5.1+/-0.5 cm; p=0.03, duration of
      exertion: 578+/-73 vs. 528+/-108 s; p=0.011, METS: 6.2+/-1.0 vs. 5.7+/-1.1;
      p=0.002, peak VO2: 22+/-3.4 vs. 20.3+/-3.4 ml/kg/min; p=0.02, VE/VCO2: 29.1+/-4.4
      vs. 33.3+/-4.7; p <0.001, VE/VCO2 slope: 23.2+/-4.7 vs. 27.5+/-5.1; p <0.001).
      The groups did not differ in peak VO2 expressed as peak VO2 % predicted and
      plasma NT-proBNP levels. Over the whole follow-up period NT-proBNP levels were
      negatively associated with LVEF, peak VO2 and MET, and positively with LVESD and
      LVEDD recorded at 3 months. In each of the analysed periods spiroergometric
      parameters significantly correlated with echocardiographic indices recorded at 3
      months. CONCLUSIONS: Early PCI for acute MI in patients aged >65 years results in
      significantly better long-term cardiovascular performance than conservative
      treatment. The patients showed the most significant improvement in LV performance
      and exercise capacity between months 3 and 6.

PMID- 19105093
TI  - Acute coronary syndrome--how to reduce the time from the onset of chest pain to
      treatment?
AB  - BACKGROUND: Enormous progress in treating acute coronary syndrome (ACS) and
      shortening the time between the onset of pain and intervention has been made in
      recent years. However, the time from the beginning of pain to the call for help
      is still too long. AIM: To establish the causes of delayed call for help by ACS
      patients and to answer the question how to shorten that time. An additional aim
      was to examine the knowledge about myocardial infarction (MI) among patients with
      ACS. METHODS: The study group consisted of 349 patients treated for ACS at the
      CCU. Nurses interviewed the patients using a questionnaire focused on demographic
      data, ACS characteristics, risk factors and situations which occurred between
      pain onset and arrival at the CCU. The data were analysed in relation to sex,
      place of living, education level, professional activity, history of MI, diabetes,
      and hypertension. RESULTS: The time between the onset of symptoms and the call
      for medical help ranged from 4 to 1140 min. The longest delay was reported by
      patients aged 56-70 years. Half of them called for help later than after 3 hours.
      Women waited longer than men. They also waited longer for an ambulance - 20 vs.
      15 min (p <0.01). Professionally active patients called for help sooner: 82.7 vs.
      120.2 min (p=0.02). Warsaw inhabitants waited longer than those living in other
      towns and in rural areas (p=0.04). The main causes of delay were: being confident
      that symptoms would subside (201 patients - 57.6%), or that the symptoms were not
      associated with heart disease (45 patients - 12.9%). The 41.5% of patients knew
      what MI was, 37.2% were familiar with features of ischaemic chest pain. Symptoms
      of pain were known to 44.4% of patients with ACS history vs. 32.2% of previously
      untreated (p=0.02), blood pressure levels were known to 51.4 vs. 45.4% (NS), and
      cholesterol to 29.9 vs. 20.0% (p=0.03). A general practitioner was mentioned as
      the source of information by 44.4% of patients and a nurse - by 11.5%.
      CONCLUSIONS: The main cause of delayed call for help in ACS patients was a poor
      level of knowledge about MI, risk factors and management at the time of chest
      pain onset. Education concerning these issues should be started at school.
      Physicians, nurses and media should participate in the education.

PMID- 19105094
TI  - Novel atherogenesis markers for identification of patients with a multivessel
      coronary artery disease.
AB  - BACKGROUND: Patients with advanced coronary artery disease (CAD) have an
      unfovourable prognosis. Therefore, early identification of this high-risk group
      is important. AIM: To asses the utility of clinical, electrographic and
      echocardiographic parameters, supported by novel atherogenesis markers, to
      identify patients with triple vessel coronary artery disease (CAD). METHODS: The
      study group comprised 37 patients (29 males, mean age 64+/-8 years) suffering
      from multivessel CAD and a control group of 16 patients (8 males, mean age 60+/
      10 years), in whom - despite typical stenocardial symptoms, positive exercise
      stress test and segmental contractility disturbances - coronary angiography did
      not reveal any haemodynamically significant CAD. Apart from coronary angiography,
      each patient had additionally an entire test panel performed assessing both the
      disease severity and the presence of other systemic dysfunction. Mean Gensini
      score in the study group was 91.9+/-43.8, including proximal Gensini score 52.6+/
      45.6 and distal one 39.4+/-29.7. RESULTS: Patients with triple vessel disease had
      a long history of angina (mean 84 months), of whom 30 (81%) experienced at least
      Q-wave myocardial infarction (MI). ECG changes typical for ischaemia were
      observed more often than in the control group. Also in patients with triple
      vessel disease echocardiography showed more escalated segmental contractility
      disorders, and left ventricular ejection fraction in this group was significantly
      lower than in the control group (44 vs. 55%, p <0.001). There were significant
      differences between CAD patients and control groups with respect to serum levels
      of: adiponectin (10.5+/-4.2 vs. 17.6+/-3 microg/ml, p=0.001), resistin (13.7+/
      6.1 vs. 7.2+/-2.4 ng/ml, p=0.007), TNF-alpha (4.2+/-2.9 vs. 2.1+/-1.1 pg/ml,
      p=0.02) and IL-8 (18.4+/-4.1 vs. 12.2+/-4.1 pg/ml, p=0.008). Significant
      differences were also noted in lipid profile (total cholesterol: 201+/-47.1 vs.
      183+/-18 mg/dl, NS; HDL cholesterol: 45+/-8.5 vs. 54+/-11 mg/dl, p=0.005; LDL
      cholesterol: 126.1+/-46.9 vs. 102+/-29 mg/dl, p=0.004), NT-proBNP [516 (174-1426)
      vs. 187 (39-573) pg/ml, p=0.02] and fasting blood glucose levels (97+/-14 vs.
      94+/-11 mg/dl, p=0.03). Significantly lower serum adiponectin levels were
      observed in men and tobacco smokers. CONCLUSIONS: Medical history, supported by
      interpretation of selected, routine imaging studies and novel biochemical
      markers, such as adiponectin, resistin, TNF-alpha, IL-8 or NT-proBNP, seem to be
      the key factors when assessing the risk of presence of advanced coronary artery
      atherosclerosis.

PMID- 19105095
TI  - Heart rate turbulence in patients with chronic heart failure.
AB  - BACKGROUND: Heart rate turbulence (HRT) has been shown to predict the prognosis
      after myocardial infarction (MI), but its prognostic value in patients with
      chronic heart failure (CHF) has not yet been well established. AIM: To evaluate
      HRT in patients with CHF and assess the prognostic significance of HRT in this
      group. METHODS: The study group consisted of 82 patients with CHF and left
      ventricular ejection fraction (LVEF) <35%. All the patients underwent 24-hour
      Holter monitoring (HM). The heart rate variability (HRV) and HRT parameters were
      assessed using HRT view software. Two HRT parameters - turbulence slope (TS) and
      turbulence onset (TO), were calculated. We analysed the clinical course and
      survival during a two-year follow-up (mean 25+/-9 months). RESULTS: The patients
      were divided into three groups according to the HRT parameters. Group 1 (23
      patients) with both normal TO and TS (TO <0%, TS >2.5 m/s), group 2 (30 patients)
      with abnormal TO or TS, group 3 (29 patients) with abnormal TO and TS (TO >0% and
      TS <2.5 m/s). Patients from group 1 was significantly younger. There were no
      differences between patients in aetiology, treatment and the frequency of
      ventricular premature beats. Significant correlations between HRV and HRT
      parameters were observed. The correlation was the strongest between TS and SDNN
      and LF. During the follow-up 9 patients died and 15 were hospitalised for non
      fatal infarction or worsening of CHF. Using a multivariate logistic regression
      model, it was shown that TS <2.5 ms/RR interval, and non-sustained ventricular
      tachycardia (VT) significantly increased the risk of a serious cardiac events in
      CHF patients. CONCLUSION: HRT parameters are often abnormal in patients with CHF.
      An abnormal turbulence slope (TS) and VT episodes are significantly associated
      with increased risk of cardiac complications in CHF.

PMID- 19105096
TI  - Impairment of arterial distensibility in premenopausal women with systemic lupus
      erythematosus.
AB  - BACKGROUND AND AIM: Systemic lupus erythematosus (SLE) is a chronic inflammatory
      autoimmune disease affecting young women and is associated with increased
      frequency of atherosclerotic vascular diseases. Pulse wave velocity (PWV) is an
      index of arterial stiffness and a marker of cardiovascular events. This study
      aimed to investigate arterial distensibility using carotid-femoral (aortic) PWV
      measurements in premenopausal women with SLE. METHODS: We recruited 24
      premenopausal women with SLE (SLE duration: 5.3+/-4.6 years) and 24 age- and sex
      matched controls. Aortic PWV was determined by using an automatic device, the
      Complior Colson (France), which allowed on-line pulse wave recording and
      automatic calculation of PWV. RESULTS: The carotid-femoral PWV (8.98+/-2.05 vs.
      8.05+/-0.94 m/s), systolic blood pressure (117.08+/-17.12 vs. 106.87+/-11.96
      mmHg), pulse pressure (45.62+/-11.91 vs. 38.33+/-9.04 mmHg), heart rate (81.41+/
      9.20 vs. 71.12+/-10.32 beat/min) and serum glucose levels (89.68+/-8.12 vs.
      73.80+/-10.72 mg/dl) were significantly higher in premenopausal women with SLE,
      as compared with control subjects (p=0.04, p=0.02, p=0.02, p=0.001, p <0.001,
      respectively). We found a significant correlation between PWV and age, body mass
      index, waist--to-hip ratio, heart rate and blood pressure. CONCLUSION: Arterial
      distensibility is decreased in premenopausal women with SLE.

PMID- 19105097
TI  - [Use of intermittent ultrafiltration in decompensated, diuretic-resistant heart
      failure--six case reports].
AB  - Veno/venous ultrafiltration is a novel alternative method of treatment in
      patients with decompensated heart failure with fluid retention. Intermittent
      ultrafiltration treatment was used in 6 patients (mean age of 58+/-2 years) with
      decompensated heart failure and volume overload occurring despite optimal
      pharmacological treatment. Patients received 3.5+/-1 ultrafiltration treatments,
      with each treatment removing 2500+/-200 ml of fluid. There were no significant
      procedure-related complications. One patient died due to progression of heart
      failure whereas 5 patients were successfully discharged from hospital on oral
      furosemide.

PMID- 19105098
TI  - Gastrointestinal haemorrhage after off-pump coronary artery bypass.
AB  - Gastrointestinal haemorrhage secondary to off-pump coronary artery bypass
      grafting (OPCABG) surgery is uncommon but lethal. We describe an 83-year-old male
      patient who developed gastrointestinal haemorrhage after successful off-pump
      CABG. He received intensive treatment, but further deteriorated following
      noradrenaline infusion, and subsequently died six days after surgery. Off-pump
      technique in combination with an extensive calcified arterial system could lead
      to mesenteric ischaemia accounting for the postoperative gastrointestinal
      haemorrhage, which might be exacerbated by the use of noradrenaline in this
      octogenarian patient.

PMID- 19105099
TI  - Heart failure caused by cardiac rhabdomyosarcoma.
AB  - Rhabdomyosarcoma accounts for 20% of primary malignant cardiac tumours. We
      describe a woman with cardiac rhabdomyosarcoma. She had loss of appetite, loss of
      weight, and symptoms of heart failure. A mobile tumour in the left atrium,
      entering the left ventricle during diastole, was detected by transthoracic
      echocardiography. The tumour was removed surgically in total; histological
      diagnosis was rhabdomyosarcoma; however, the patient died after 6 months. In
      conclusion, primary malignant cardiac tumours can simulate heart failure or
      systemic disorders. Cardiac rhabdomyosarcomas have a poor prognosis with average
      survival of 6 months after diagnosis.

PMID- 19105100
TI  - [Triple therapy. Bad luck... or don't we still know how to treat?].
AB  - A case of a 65 year old male with acute myocardial infarction treated with
      primary angioplasty and stent implantation is presented. Following infarction,
      the patient suffered twice from the in-stent thrombosis in spite of triple
      antiplatelet/anticoagulant therapy. The problem of recurrent restenosis in spite
      of optimal therapy is discussed.

PMID- 19105101
TI  - [Disturbances in mitochondrial biosynthesis of acetyl-CoA and their role in the
      prevention of ischemic heart disease].

PMID- 19105102
TI  - [Proarrhythmic effect of propafenone in patients with atrial fibrillation and
      atrial flutter].
AB  - We present two cases of proarrhythmia after propafenone treatment. In the first
      case slowing of the flutter cycle length from 205 ms to 290 ms resulted in a
      change from well tolerated two to one atrioventricular conduction to one to one
      conduction with hypotension and presyncope. In the second case organization of
      atrial fibrillation to atypical atrial flutter and use-dependent left bundle
      branch block resulted in fast broad QRS tachycardia that mimicked ventricular
      tachycardia.

PMID- 19105103
TI  - [Late infective mechanical aortic valve prosthesis endocarditis].
AB  - We present a case of late infective endocarditis on the mechanical aortic valve
      prosthesis, complicated by large paraortic abscesus. It was dificult to diagnosed
      this patient, because of negative blood cultures results and not diagnostic view
      in transthoracic echocardiogram. Transesophageal echo was performed just before
      cardiac surgery because of very bad patient's condition.

PMID- 19105104
TI  - [Balloon angioplasty for the treatment of the drug-eluting stent restenosis in a
      patient with multivessel coronary artery disease and muscular bridge].

PMID- 19105105
TI  - [Radiofrequency ablation of long standing persistent atrial fibrillation and post
      incisional macroreentrant right atrial tachycardia in patient with advanced
      biventricular heart failure--case raport].
AB  - We present a case of a 54 year old male with a long-standing atrial fibrillation
      (AF) who was scheduled for cardiac transplantation due to the progression of
      heart failure. Previous treatment included pacemaker implantation, mitral
      valvuloplasty, a-v node modification using RF ablation, and pharmacological
      therapy. This time the patient underwent complex AF ablation which consisted of
      pulmonary vein isolation, mitral and left atrial roof line creation, cavo
      tricuspid isthmus ablation and ablation of complex fractionated atrial
      electrograms, which resulted in restoration of sinus rhythm. Because of the right
      atrial post-incisional tachycardia the patient underwent second ablation session.
      This complex invasive approach occurred successful. The patient remains in sinus
      rhythm with improved left ventricular function and better NYHA class over a 12
      month follow-up.

PMID- 19105106
TI  - Polish forum for prevention guidelines on dyslipidaemia.

PMID- 19105107
TI  - Interobserver agreement in perfusion computed tomography evaluation in acute
      ischaemic stroke.
AB  - BACKGROUND AND PURPOSE: A growing body of evidence suggests that semiquantitative
      assessment of perfusion computed tomography (PCT) may improve evaluation of acute
      ischaemic stroke patients and provide some prognostic values. The Alberta Stroke
      Program Early CT Score (ASPECTS) is one of the tools quantifying ischaemic
      changes on CT scans. While introducing PCT for routine evaluation of patients
      with clinical suspicion of acute stroke in our Neurology Department, we aimed to
      investigate the agreement in analysis of non-contrast CT (NCCT) and PCT using
      ASPECTS between neuroradiologists and stroke neurologists. MATERIAL AND METHODS:
      We analyzed the data of 34 patients with hemispheric ischaemic stroke, in whom
      NCCT and PCT were performed within 12 hours after stroke onset. Two pairs of
      reviewers independently assessed NCCT and PCT [colour-coded maps of cerebral
      blood flow (CBF), cerebral blood volume (CBV), and time-to-peak (TTP)] using
      ASPECTS. Based on the literature data, we dichotomized the score. The chosen cut
      off points were: 6 vs. <6, 7 vs. <7, and 8 vs. <8. The agreement was determined
      using kappa statistics. RESULTS: A better agreement was achieved for PCT maps
      compared with NCCT scans and when the cut-off point was 7 vs. <7. The results
      were as follows: for NCCT fair agreement (k=0.27), for CBF and for CBV moderate
      agreement (k=0.46 and k=0.57, respectively), for TTP substantial agreement
      (k=0.77). CONCLUSIONS: A good agreement in semiquantitative assessment of PCT
      using ASPECTS indicates that it is a reliable tool to analyze acute ischaemic
      stroke patients and superior to NCCT.

PMID- 19105108
TI  - Perfusion computed tomography and clinical status of patients with acute
      ischaemic stroke.
AB  - BACKGROUND AND PURPOSE: There is increasing availability of perfusion computed
      tomography (PCT) for assessment of acute ischaemic stroke patients. A
      semiquantitative evaluation of CT scans can be easily and quickly performed by
      the examining physician. In the current study, we investigated the correlation
      between the Alberta Stroke Program Early CT Score (ASPECTS) quantifying acute
      ischaemic changes on CT scans and clinical status of ischaemic stroke patients.
      MATERIAL AND METHODS: We analyzed the data of 34 patients with hemispheric
      ischaemic stroke, in whom both non-contrast CT (NCCT) and PCT were performed
      within 12 hours after stroke onset. NCCT and PCT [colour-coded maps of cerebral
      blood flow (CBF), cerebral blood volume (CBV), and time-to-peak (TTP)] were
      evaluated using ASPECTS. The correlations between ASPECTS and severity of
      neurological deficit, and prognostic value of ASPECTS for long-term clinical
      outcome were studied. RESULTS: We found a significant correlation between the
      baseline clinical status and ASPECTS for all CT techniques as well as between CBV
      and neurological deficit at discharge. ASPECTS l7 in all CT techniques had a high
      sensitivity and positive predictive value for prognosis of 3-month functional
      independency. CONCLUSIONS: ASPECTS used for PCT and NCCT shows a good correlation
      with clinical status and prognosis of ischaemic stroke patients.

PMID- 19105109
TI  - Direct and remote outcome after treatment of tumours involving the cavernous
      sinus and its surroundings.
AB  - BACKGROUND AND PURPOSE: The aim of this study was to present results obtained by
      the authors after surgical treatment of tumours involving the cavernous sinus
      (CS) and its surroundings. MATERIAL AND METHODS: Thirty-eight patients (23
      females and 15 males) with tumours of the CS and its surroundings were included
      in the study. The neurological condition of patients and their ability to perform
      activities of daily living were evaluated prior to treatment, postoperatively and
      after completion of therapy. The following parameters were measured: approximate
      volume of the operated lesions; their relation to larger vessels, cranial nerves
      and the brainstem; consistency and vascularization. RESULTS: The medical history
      of the disease ranged from 1.5 to 48 months, mean 12 months. In 89.5% of cases
      impaired ocular motility on the side of the lesion was the symptom indicative of
      the condition. The second most common group of symptoms (29%) included
      impairments of trigeminal nerve function. The approximate volume of all resected
      tumours ranged from 0.6 to 60 mL (mean 12.2 mL). In 50% of cases the resected
      tumours were diagnosed as meningiomas. The remaining entities included:
      perithelioma, hypophyseal adenoma, adenoid cystic carcinoma, neuroendocrine
      carcinoma, trigeminal neurinoma, chordoma, cavernous angioma and lymphoma. In 63%
      resections were complete. Functional capacity of patients improved in 34% of
      cases, remained unchanged in 53%, deteriorated in 10.5%, and one patient died.
      CONCLUSIONS: Surgical intervention involving the CS and its surroundings enables
      resection of neoplastic tumours of this anatomical region with satisfactory
      clinical results and low mortality. Most patients suffer from temporary paresis
      or paralysis of the oculomotor, trochlear and abducent nerves. Reduction of
      completeness of resections of CS tumours decreases the number of postoperative
      neurological deficits without a significant increase in the rate of lesion
      regrowth.

PMID- 19105110
TI  - Cognitive impairment in patients with relapsing-remitting multiple sclerosis. The
      correlation with MRI lesion volume.
AB  - BACKGROUND AND PURPOSE: The aim of this study was to assess cognitive impairment
      in patients with relapsing-remitting multiple sclerosis (RR-MS) and to evaluate
      the correlation of cognitive impairment with physical disability and MRI lesion
      volume. MATERIAL AND METHODS: Sixty patients with RR-MS and 50 healthy controls
      were assessed using neuropsychological tests. All the patients were subjected to
      MRI examination using PD/T2 and T1 sequences, and clinical evaluation with the
      EDSS scale was applied. RESULTS: Selective cognitive impairment was found in 40%
      of the RR-MS group, and broad, overall cognitive dysfunction was found in 15% of
      patients. A correlation was found between neurological signs and memory deficits
      and psychomotor speed. The mean total lesion volume (TLV) was significantly
      higher in patients with selective and overall cognitive impairment than in those
      without (8060 vs. 3183 mm3, p=0.001; 7234 vs. 3138 mm3, p=0.004, respectively).
      There was no difference in TLV between RR-MS patients with selective or overall
      cognitive impairment (8060 vs. 7234 mm3, p=0.134). Moderate correlations were
      found between nonverbal memory, verbal fluency and abstract reasoning tests and
      TLV. CONCLUSIONS: Cognitive impairment is present in more than 50% of patients
      with RR-MS, and they are mainly selective deficits. The correlation between
      physical disability and cognitive impairment was not significant, except for
      memory deficits and psychomotor speed. There is a correlation between TLV and
      presence of cognitive impairment, but no correlation between TLV and pattern of
      cognitive impairment.

PMID- 19105111
TI  - [Selected problems from the descriptive and surgical anatomy of the cavernous
      sinus].
AB  - The paper contains anatomical information concerning the cavernous sinus (CS) and
      the structures related to it topographically and constituting its direct
      surroundings. This information is a starting point for surgical interference in
      the CS, as well as a background for analyzing the clinical problems of CS
      disorders and the results of their surgical treatment. After considering
      developmental conditioning, the structure of three walls of the cavernous sinus
      was discussed: the medial, superior and lateral one. This enabled a precise
      topography of the cranial nerves connected with the CS to be created. The author
      sets forth information on the role of the CS as one of the main venous passages
      within the cranial cavity. The article describes the segments of the internal
      carotid artery which are connected with the CS. Moreover, it discusses the
      intracavernous branches of the artery and the range of their vascularisation. The
      paper ends with an analysis of the possible ways of surgical interference in CS,
      known as 'CS triangles'.

PMID- 19105112
TI  - [Lateral approach to the cavernous sinus and its surroundings--analysis of
      surgical technique based on cadaver simulations].
AB  - BACKGROUND AND PURPOSE: The paper aims to present individual stages of a surgical
      approach to the cavernous sinus (CS) and its surroundings. MATERIAL AND METHODS:
      Twelve simulations of a surgical approach to the CS and its surroundings were
      performed in non-fixed cadavers. The subsequent stages of simulation were
      recorded in photographs and drawings. RESULTS: The starting point for the
      approach to the CS is a pterional craniotomy, as well as an osteotomy
      encompassing the anterior clinoid process and the surroundings of the superior
      orbital fissure, the optic canal, the foramen rotundum and the foramen ovale. The
      important phases of the approach include the delamination of the lateral CS wall
      and the mobilization of the dural rings of the internal carotid artery. Opening
      of the CS should be preceded with establishing proximal and distal control over
      the internal carotid artery. CONCLUSIONS: The surgical approach to the CS and its
      surroundings constitutes a repeatable method of penetration in this area of the
      cranial base, and it allows for limiting brain traction and preserving the
      anatomical integrity of the related vessel and nerve structures.

PMID- 19105113
TI  - [Cerebrospinal fluid markers of prion diseases].
AB  - There are no non-invasive tests allowing for definite premortem diagnosis of
      Creutzfeldt-Jakob disease (CJD). The paper presents the current knowledge about
      laboratory tests supporting CJD diagnosis. 14-3-3 protein in the cerebrospinal
      fluid is the only biochemical marker included in the diagnostic criteria for CJD
      approved by WHO. However, the test for 14-3-3 protein is useful only when
      considered in an appropriate clinical context, together with other diagnostic
      criteria. In the paper we also present current research in the use of other
      proteins detected in the cerebrospinal fluid (tau, S100b, neuron-specific
      enolase, transthyretin, and beta-amyloid1-42 as potential diagnostic markers. We
      discuss advantages and drawbacks of these markers.

PMID- 19105114
TI  - Mechanical embolectomy in acute ischaemic stroke--report of the first two cases.
AB  - Intravenous thrombolysis is the only approved treatment for acute ischaemic
      stroke administered within 3 hours of onset. Mechanical embolectomy with the
      MERCI device is a new treatment option for patients with occlusion of a large
      cerebral artery who do not meet the current license criteria for thrombolysis,
      are admitted up to 15 hours from onset, or do not respond to treatment with
      recombinant tissue plasminogen activator (rt-PA). This is a report of the first
      two cases of acute ischaemic stroke treated with the MERCI device at our
      department. One did not meet the inclusion criteria for systemic thrombolysis,
      and the second did not improve despite rt-PA treatment. In both cases improvement
      of flow in the MCA was achieved and moderate neurological improvement was
      observed at 3-month follow-up. More studies and controlled trials are needed to
      establish the utility of mechanical embolectomy in the treatment of stroke.

PMID- 19105115
TI  - Acute disseminated encephalomyelitis: a report of two fulminant cases and review
      of literature.
AB  - Although the prognosis of acute disseminated encephalitis (ADEM) has generally
      been reported as favorable, in a small subset of patients, fulminant cerebral
      edema requiring critical care and surgical management may develop. This article
      presents a 56-year-old woman who developed ADEM and died of central brain
      herniation secondary to medically intractable cerebral edema. Following this
      experience, we encountered a 32-year-old man who also developed central brain
      herniation despite best medical management. We performed an urgent decompressive
      hemicraniectomy and frontal lobectomy followed by intensive intracranial pressure
      management. Few recommendations are available to guide neurologists and
      neurosurgeons in the management of medically intractable cerebral edema of ADEM.
      In this report, we present our experience with two severe cases of ADEM, review
      the pertinent literature, and discuss options for improved management of
      fulminant cases.

PMID- 19105116
TI  - Paraganglioma of cauda equina.
AB  - The clinical, radiological and pathological features of a paraganglioma resulting
      in cauda equina syndrome are described, including magnetic resonance imaging
      features. The literature is reviewed and discussed.

PMID- 19105117
TI  - Giant ossifying fibroma complicated by mucocele of sphenoid sinus--case report.
AB  - Ossifying fibroma is a benign tumour that rarely involves the skull. It is most
      commonly seen in the facial bones with a particular predilection for the
      mandible. It shares many pathological features with fibrous dysplasia. Ossifying
      fibroma is an expansive lesion and shows larger non-ossified areas of fibrous
      tissues. When the tumour is located deeply, encasing the optic-carotid complex,
      surgical removal becomes difficult because of its ossifying nature. Following
      surgical resection, the recurrence rate is very low. In the present study, a rare
      case of giant ossifying fibroma of sphenoid bone which had an intracranial
      extension with a coexistent mucocele is reported.

PMID- 19105118
TI  - [Isolated tremor of the head].

PMID- 19105119
TI  - Classifying Africans with the metabolic syndrome.
AB  - This study was aimed to compare prevalences of the metabolic syndrome in Africans
      using five definitions as proposed by the World Health Organization (WHO), the
      European Group for the Study of Insulin Resistance (EGIR), the National
      Cholesterol Education Program Expert Panel on Detection, Evaluation, and
      Treatment of High Blood Cholesterol in Adults [Adult Treatment Panel (ATPIII)],
      the American College of Endocrinology (ACE), and the International Diabetes
      Federation (IDF). A further objective was to identify difficulties in classifying
      Africans with the metabolic syndrome and to suggest specific areas where criteria
      adjustments for identifying Africans should be made. A case-case-control cross
      sectional study involved 102 urban African women. Except for microalbumin data,
      all data necessary for classification of the metabolic syndrome were collected,
      including fasting and 2-h glucose and insulin, anthropometric measurements, blood
      pressure, and lipids. The metabolic syndrome prevalences ranged from 5.4% (EGIR),
      15.7% (ATPIII), >or=19.4% (WHO), 24.8% (IDF) to 25.5% (ACE). Only 2.9% (n=3) had
      a triglyceride level >or=1.69 mmol/l, but 58.8% (n=60) had a HDL-level <1.29
      mmol/l, whereas 27% (n=26) were insulin resistant, 22.3% (n=21), had a blood
      pressure >or=140/90 or used hypertension medication. It seems as if the
      classification of hypertension, insulin resistance and hyperglycemia might have
      been adequate, but body composition and dyslipidemia criteria need adjustment for
      Africans. Since neither definition seems completely suitable for Africans it is
      suggested that clinical emphasis should rather be on treating any specific
      cardiovascular disease risk factor that is present, than on diagnosing a patient
      with the metabolic syndrome.

PMID- 19105120
TI  - [Influence of mixing ratios of a FM-system on speech understanding of CI-users].
AB  - BACKGROUND: At school we find two major acoustic situations: (first) the "teacher
      is talking" being disturbed by the pupils making noise and (second) another
      "pupil is talking" disturbed by other pupils. The understanding of words and
      sentences in hearing impaired patients with a cochlear implant (CI) in a noisy
      situation can be improved by using a FM system. The aim of this study is to test
      speech understanding depending on mixing ratios between FM input and microphone
      input to the speech processor in different circumstances. METHODS: Speech
      understanding was evaluated using the adaptive Oldenburger sentence test (OLSA)
      in background noise. CI patients used the FM system Microlink for Freedom CIs
      together with a Campus transmitter (Phonak AG). PATIENTS: 17 postlingually
      deafened adults were tested, using unilateral Freedom cochlear implant systems
      (Cochlear Ltd). A group of eight normally hearing adults was used as a control
      group in the same setup. RESULTS: We found that the median value of L (50)=1.6 dB
      in CI patients without a FM system is higher than the median value of L(50)=-13
      dB in normally hearing subjects. The sentence recognition in CI patients with FM
      system increased with increasing mixing ratio. The benefit using the FM system to
      understand the teacher is of high advantage in any mixing ratio. The difference
      between the L(50) values in situations with or without a FM-system is 15 dB for
      the mixing ratio 3:1 (FM to microphone). If we take into account an increase of
      15% per dB in the OLSA (at L(50)) in CI patients, the difference of 15 dB means a
      calculated advantage of 225%. The speech understanding during the second
      condition ("pupil is talking") however remained nearly the same in all used
      mixing ratios. The calculations showed no statistical difference between these
      situations with and without a FM system. CONCLUSION: The speaker comprehension
      for the two investigated listening conditions showed different results.
      Understanding in the "teacher is talking" situation increased with increasing
      mixing ratio (FM to microphone) and in the "pupil is talking" situation remained
      on the same level. We could not find an optimal FM setting for both listening
      conditions. This leads to different suggestions for different listening
      conditions. All patients showed an increased speech understanding in noisy
      environments. This result strongly encourages the use of a FM-system in a
      classroom.

PMID- 19105122
TI  - Prepared for the future?

PMID- 19105121
TI  - [First experiences with the new soft-clip piston as an alloplastic prosthesis
      during stapedotomy].
AB  - INTRODUCTION: A large variety of prostheses are available for stapes surgery. The
      newly designed Soft-CliP Piston is an alloplastic prosthesis used in patients
      with Otosclerosis which has been available since May 2007. With the new design,
      an intra- and postoperative damage of the ossicle chain should be minimized.
      PATIENTS AND METHODS: A Laser-Stapedotomy was performed in 11 patients with a
      mean age of 45.7 years. Soft-CliP pistons with a shaft diameter of 0.4 mm and a
      length of 4.5 mm were used. An accurate examination and an exact audiometric
      testing were performed pre- and postoperative. RESULTS: The average observed air
      bone-gap in the frequencies from 0.5 to 4 kHz was postoperatively in 2.9% of the
      patients greater than 20 dB, in 5.7% between 15-20 dB, in 14.3% between 10-15 dB
      and less than 10 dB in 77.1% of the patients. Despite the new design of the
      prostheses it wasn't possible to slit the prosthesis onto the incus in two cases,
      and in one case there wasn't the needed size available. CONCLUSION: A critical
      point in every stapes surgery, the prosthesis fixation onto the incus, is
      facilitated by the novel Soft-CliP Piston. Crimping is not needed anymore. Very
      good hearing results are achieved postoperatively, comparable to other Titanium
      Prostheses. However the surgeon needs adequate experience to insert the Soft-CliP
      Piston. Long-term results in a larger group of patients are needed and pending.

PMID- 19105123
TI  - Time for a change.

PMID- 19105126
TI  - [Diffusion-weighted magnetic resonance imaging (DWI-MRI): a new method to
      differentiate between malignant and benign cervical lymph nodes].

PMID- 19105127
TI  - Venous malformation of the neck with giant phleboliths.
AB  - We present a case involving a 76-year-old man with a massive right-sided vascular
      neck mass that had been present since birth. The mass had been stable throughout
      the patient's life, but recently a portion of it had become hard. Physical
      examination revealed a firm, palpable focus within the vascular lesion in the
      right side of the neck. Computed tomography revealed the presence of numerous
      hyperdense foci, many more than 2 cm in size, which were confirmed by fine-needle
      aspiration to be phleboliths. The patient was followed for 6 months to ensure
      that the vascular mass and phleboliths remained stable.

PMID- 19105128
TI  - Suture medialization of the middle turbinates during endoscopic sinus surgery.
AB  - Adhesion of the middle turbinate to the lateral nasal wall is a common
      complication of endoscopic sinus surgery. The potential sequela of middle
      turbinate lateralization is obstruction of the middle meatus and the maxillary,
      ethmoid, or frontal sinuses, which can result in recurrent sinus disease and
      often necessitate revision surgery. While various materials and stents have been
      developed to prevent middle turbinate adhesion to the lateral nasal wall, suture
      medialization of the middle turbinate to the nasal septum with an absorbable
      suture has the potential to be just as successful without causing the discomfort
      associated with other methods. We conducted a retrospective review of suture
      medializations of 157 middle turbinates in 85 patients who had undergone
      endoscopic sinus surgery to ascertain the incidence of postoperative middle
      turbinate adhesion to the lateral nasal wall. We found that adhesions developed
      in 17 middle turbinates (10.8%) in 15 patients; the remaining 140 middle
      turbinates (89.2%) were free of scarring. Thirteen of the 17 adhesions were
      easily divided in the outpatient clinic setting during routine postoperative
      endoscopic care, meaning that only 4 of the 157 turbinates (2.5%) demonstrated
      synechiae that remained problematic after routine care. We conclude that the
      development of clinically significant adhesions following suture medialization of
      the middle turbinate is uncommon. Suture medialization should be considered as an
      alternative to middle meatal packing or stenting to prevent adhesions following
      endoscopic sinus surgery.

PMID- 19105129
TI  - Nasopharyngeal neuroendocrine carcinoma: a case report.
AB  - Neuroendocrine carcinoma is a type of neuroendocrine system neoplasm that occurs
      in organisms in which amine precursor uptake and decarboxylation (APUD) cells are
      uncommon. In the human body, the most common sites of neuroendocrine carcinoma
      are the gastrointestinal tract and the lungs. From a histologic standpoint, these
      tumors are identified by their positive reaction to silver stains and specific
      markers for neuroendocrine tissues, such as chromogranin A, synaptophysin, and
      neuron-specific enolase. In addition to local symptoms, these tumors may cause
      flushing, wheezing, and episodic diarrhea secondary to the release of vasoactive
      substances. Our medline search encompassing the 20-year period prior to 2003
      found few cases of this type of tumor in the paranasal sinuses and nasal cavities
      and only 1 case of an isolated neuroendocrine carcinoma in the nasopharynx. We
      describe another case of an isolated nasopharyngeal neuroendocrine carcinoma,
      which we observed in a 74-year-old woman. We review the clinical presentation and
      the surgical and systemic treatment.

PMID- 19105130
TI  - The prevalence of hearing loss among schoolchildren with chronic suppurative
      otitis media in Nigeria, and its effect on academic performance.
AB  - We conducted a cross-sectional study to determine the prevalence of hearing loss
      among 1,500 Nigerian schoolchildren aged 9 to 15 years who had chronic
      suppurative otitis media (CSOM). We also attempted to ascertain the effect that
      this hearing loss had on their academic performance. The study population was
      drawn from three schools in different socioeconomic tiers-low (n = 300), medium
      (n = 400), and high (n = 800). Overall, CSOM was present in 35 of these children
      (2.3%)-12 from the low-status school (4.0%), 11 from the middle-status school
      (2.8%), and 12 from the high-status school (1.5%); the overall difference in
      prevalence among the three schools was statistically significant (chi(2) = 6.40;
      degrees of freedom [df] = 2; p = 0.04). In all, 52 ears were affected by CSOM; of
      these, 18 (34.6%) had a pure-tone average (PTA) within normal limits, 20 (38.5%)
      had a mild conductive hearing loss, and 14 (26.9%) had a moderate loss. All but 2
      of 160 control ears (1.2%) had hearing thresholds within normal limits. The
      difference in PTAs across groups was statistically significant (chi(2) = 114.89;
      df = 2; p< 0.001). As for academic performance, cumulative average test scores
      were significantly lower in the CSOM patients than in the controls-chi(2) =
      14.57; df = 3; p = 0.002. At the higher end of the academic scale, scores of 66%
      and higher were obtained by 40.0% of patients and 51.3% of controls, and scores
      of 50 to 65% were achieved by 20.0% of patients and 37.5% of controls. At the
      lower end, scores of 40 to 49% were obtained by 31.4% of patients and 6.3% of
      controls, and scores of 39% and lower were obtained by 8.6% and 5.0%,
      respectively. We conclude that hearing loss was a significant sequela of CSOM in
      our study population and that it had an adverse effect on their academic
      performance. Children in the low socioeconomic group appeared to be more
      vulnerable.

PMID- 19105131
TI  - Nasopharyngeal angiofibroma: rare presentations.
AB  - Nasopharyngeal angiofibromas are benign tumors of the nasopharynx that occur in
      adolescent boys. The extensive extensions and various clinical presentations of
      the tumor have been well documented in the literature. Very rarely, these tumors
      may extend outside the nasal cavity as a large polypoid mass. Two interesting
      cases of angiofibroma with atypical presentations, showing extensive spread in
      multiple directions, are reported here. In one case, the angiofibroma exited the
      right nostril as a large polypoidal mass and also presented as an intraoral tumor
      in the right upper gingivo-alveolar region. In the other case, in addition to
      polypoidal presentation through the anterior nares, the tumor produced severe
      respiratory obstruction resulting from extensive bulging of the soft palate.

PMID- 19105132
TI  - Long-term immunotherapy for perennial allergic rhinitis: relationship of specific
      IgG levels to skin-prick test results and clinical symptoms and signs.
AB  - We studied 63 adults with perennial allergic rhinitis and positive skin-prick
      tests for Dermatophagoides pteronyssinus (Dp) and Dermatophagoides farinae (Df)
      who had not previously received any type of immunotherapy or pharmacotherapy for
      their condition. We injected these patients with a 50% Dp/50% Df modified
      allergen intradermally in accordance with the classic immunotherapy scheme once a
      week for 30 months. Specific immunotherapy (SIT) was administered until the
      specific IgG (sIgG) concentration reached level IV (>or=81% absorbance). We
      measured specific IgE and sIgG levels, obtained skin-prick test results, and
      evaluated clinical symptoms and signs before immunotherapy, at 6 months into
      therapy, at the completion of therapy (30 mo), and 1 year after the completion of
      therapy. In the group as a whole, differences between mean sIgG values and mean
      skin-prick test results before and after SIT were statistically significant (p <
      0.05). At the 1-year follow-up, there was a negative correlation between sIgG
      levels and clinical symptom and sign scores, a positive correlation between skin
      prick test results and clinical improvement, and a negative correlation between
      sIgG levels and skin-prick test results. Individually, at the 1-year follow-up,
      50 of the 63 patients (79%) had experienced a resolution of clinical symptoms
      and/or signs and were thus deemed to have achieved clinical recovery.

PMID- 19105133
TI  - Recurrent infantile myofibromatosis: a report of conservative management and
      discussion of treatment strategies.
AB  - Infantile myofibromatosis is a rare proliferative mesenchymal disorder that has a
      potential for rapid growth and recurrence. Approximately 30% of infantile
      myofibromatosis lesions present in the head and neck, and some of these can cause
      significant morbidity. We report a case of recurrent infantile myofibromatosis
      that persisted after surgery and chemotherapy and was managed conservatively.
      Treatment of infantile myofibromatosis varies according to the size, location,
      and extent of disease. Solitary lesions may be simply observed in view of their
      potential for regression, but surgical excision, radiotherapy, and/or
      chemotherapy should be considered on a case-by-case basis, especially for
      nonresectable, rapidly progressive, or symptomatic lesions.

PMID- 19105134
TI  - Intratonsillar abscess: a rare cause for a common clinical presentation.
AB  - Intratonsillar abscess is a rare clinical condition in patients who present with
      odynophagia. We report the case of a 33-year-old man who presented with
      odynophagia, unilateral tonsillar enlargement with palatal fullness, and
      deviation of the uvula. Failed attempts at drainage of a presumptive
      peritonsillar abscess and a worsening of signs and symptoms led to a clinical
      suspicion of a parapharyngeal abscess. Computed tomography of the neck detected a
      2.6 x 2.3-cm intratonsillar abscess. The abscess was drained, and the patient's
      signs and symptoms resolved. Our review of the current English-language
      literature revealed that only 8 such cases have been previously reported. We
      report this new case to increase awareness of this condition, to demonstrate the
      diagnostic difficulty in such cases, and to discuss the pathophysiology of
      intratonsillar abscess formation.

PMID- 19105135
TI  - General otolaryngology and the subspecialties: finding the balance.

PMID- 19105136
TI  - The floppy vocal polyp.

PMID- 19105137
TI  - Maxillary sinus osteitis secondary to a dental implant.

PMID- 19105138
TI  - Surgical management of iatrogenic hypoglossal nerve injury.

PMID- 19105139
TI  - Temporoparietal fascia flap reconstruction of a Mohs defect of the ear.

PMID- 19105140
TI  - Acquired vascular compression of the esophagus.

PMID- 19105141
TI  - Primary stapedectomy: the surgery.

PMID- 19105142
TI  - Practice patterns in academic otolaryngology 2006: a tool for the future.
AB  - Although the American Academy of Otolaryngology-Head and Neck Surgery conducts a
      workforce survey annually, no study has been conducted to examine practice
      patterns as they pertain specifically to academic otolaryngology. Therefore, I
      developed the Academic Otolaryngologist Survey for this purpose. This survey,
      conducted in 2006, was mailed to 856 practicing otolaryngologists in the United
      States; 230 responded, for a return rate of 26.9%. Of the 230 respondents, 94%
      practiced full-time, 97% worked with otolaryngology residents and were board
      certified, and 67% had fellowship training in one or more subspecialties. The
      most commonly reported fellowships were in pediatric otolaryngology, facial
      plastic surgery, head and neck, and otology/neurotology. Respondents answered
      that they felt practice patterns had changed. Unlike the private-practice sector,
      academic otolaryngology is seeing a shift from generalists to subspecialists. The
      subspecialization becoming prevalent in academic otolaryngology may ultimately
      alter resident training. Therefore, academic programs need a balance of general
      and subspecialized otolaryngologists in order to train residents for practice.

PMID- 19105143
TI  - Middle ear barotrauma with hyperbaric oxygen therapy: incidence and the
      predictive value of the nine-step inflation/deflation test and otoscopy.
AB  - We conducted a prospective study to determine the incidence of middle ear
      barotrauma in patients who were undergoing hyperbaric oxygen therapy (HBOT). We
      also investigated the value of the nine-step inflation/deflation test and
      otoscopic findings before and immediately after the initial HBOT session in
      predicting barotrauma in an attempt to establish some criteria for prophylaxis.
      The study was conducted on 36 ears of 18 adults who had no history of eustachian
      tube dysfunction. Patients were being treated with HBOT for sudden hearing loss,
      wound-healing complications, or complications of diabetes. After 7 days of HBOT,
      barotrauma was seen in 12 of the 18 patients (66.7%) and in 18 of the 36 ears
      (50.0%). The nine-step inflation/deflation tests, which were performed before and
      immediately after the initial HBOT session, were not predictive of barotrauma (p
      = 0.095 before and p = 0.099 after). However, otoscopic findings obtained
      immediately after the first session of HBOT were predictive of barotrauma, with a
      sensitivity and specificity of 83 and 100%, respectively. We conclude that
      patients with even minor positive pathologic findings on otoscopy immediately
      following HBOT are at increased risk of middle ear barotrauma if HBOT is to be
      continued without prophylaxis.

PMID- 19105144
TI  - Noise exposure levels in stock car auto racing.
AB  - Noise-induced hearing loss associated with the workplace has been well described.
      Far less is known, however, about the risks to hearing from recreational sources
      of noise. We investigated the popular sport of stock car racing as a potentially
      significant source of noise exposure, and we conducted a sound-level survey at a
      National Association for Stock Car Auto Racing (NASCAR) event. Noise levels
      measured during the race ranged from 96.5 to 104 dB(A) at 46 meters (
      approximately 150 feet) from the track and 99 to 109 dB(A) at 6 meters (
      approximately 20 feet) from the track. The peak sound pressure level at 6 meters
      was 109 dB(A). Although significantly less than that associated with an immediate
      permanent threshold shift, such an exposure could cause a temporary threshold
      shift. Alhough hearing protection is recommended, particularly for track
      employees with longer periods of exposure, racing fans with only occasional
      exposure to such noise levels are unlikely to develop a permanent noise-induced
      hearing loss.

PMID- 19105145
TI  - Transantral endoscopic repair of orbital floor fractures with the use of a
      flexible endoscope holder: a cadaver study.
AB  - We conducted a cadaver study to determine the ease of use and functionality of a
      flexible endoscope holder in the visualization and repair of orbital floor
      fractures via a transantral approach. Four fresh cadaver heads were dissected
      through a sublabial antrotomy incision with a 30 degrees endoscope attached to a
      flexible holder. An implant was placed to restore the normal anatomy. With the
      use of this exclusive endoscopic approach, all orbital floor fractures were
      identified in their entirety and completely reduced with alloplastic material. We
      conclude that the flexible endoscope holder provides clearer visualization,
      greater instrument mobility, and an overall superior dissection and placement of
      implants in the endoscopic repair of orbital floor fractures.

PMID- 19105146
TI  - Nasoseptal chondrosarcoma resection requiring anterior fossa floor repair: a case
      report.
AB  - We present a case in which a 23-year-old male patient diagnosed with nasoseptal
      chondrosarcoma with anterior cranial fossa extension underwent combined surgical
      approaches to optimize complete resection of the tumor. Surgery was followed by a
      6-month course of proton-beam radiation therapy. Extensive tumors of this type
      with significant intracranial extension require surgical repair of the anterior
      fossa floor. We employed a repair technique not previously associated with the
      resection of these tumors, using a split-calvaria osteoplastic rotational flap.
      This method provided structural integrity while avoiding the risks associated
      with the use of free bone grafts and metallic meshes.

PMID- 19105147
TI  - Intravascular papillary endothelial hyperplasia (Masson lesion) of the
      hypopharynx and larynx.
AB  - Masson lesion is characterized by a benign intravascular papillary hyperplasia
      and subsequent thrombosis. Clinically, this lesion can be misdiagnosed as
      mucocele, hemangioma, Kaposi sarcoma, angiosarcoma, pyogenic granuloma, and
      several other lesions. In this article, we report a case of intravascular
      papillary endothelial hyperplasia of the hypopharynx and larynx, which caused
      dysphagia in an 18-year-old female patient. The lesion was excised entirely via a
      lateral pharyngotomy approach. We discuss the clinical and histopathologic
      features, differential diagnosis, and treatment of this uncommon entity.

PMID- 19105148
TI  - Pharmacodynamic effect of iopanoic acid on free T(3) and T(4) levels in
      amiodarone-induced thyrotoxicosis.
AB  - We describe the effects of iopanoic acid on daily levels of free triiodothyronine
      (FT(3)) and free thyroxine (FT(4)) in a patient with progressive type II
      amiodarone-induced thyrotoxicosis (AIT) who was undergoing thyroidectomy. The
      patient was a 59-year-old man who was undergoing amiodarone therapy while
      awaiting cardiac transplantation; the use of beta blockers and corticosteroids to
      control the AIT was contraindicated in this patient. Prior to thyroidectomy, the
      patient was started on iopanoic acid at 1.0 g twice a day; in response to
      gastrointestinal side effects, the dosage was subsequently reduced to 0.5 g twice
      a day. The patient responded to iopanoic acid with a rapid decrease in his FT(3)
      level and slight increase in his FT(4) level. This control of thyrotoxicosis
      allowed for an uneventful thyroidectomy, which was later followed by successful
      cardiac transplantation. Based on our findings in this single case, we believe
      that iopanoic can be used to rapidly lower FT(3) levels and to treat symptoms of
      thyrotoxicosis in a preoperative setting. We also discuss the different
      pharmacodynamic effects that iopanoic acid has on FT(3) and FT(4) levels.

PMID- 19105149
TI  - [Pre-test and post-test probabilities. Who cares?].
AB  - The accuracy of a diagnostic test, i.e. abdomen ultrasound in patients with
      suspected acute appendicitis, is described in the terms of sensitivity and
      specificity. According to eminent textbooks physicians should use the values of
      the sensitivity and specificity of a test in their diagnostic reasoning.
      Physician's estimate, after taking the history, the pretest-probability of the
      suspected illness, order one or more tests and then calculate the respective
      posttest-probability. In practice physicians almost never follow this line of
      thinking. The main reasons are; to estimate concrete illness probabilities is
      difficult, the values for the sensitivity and specificity of a test are most
      often not known by physicians and calculations during daily practice are
      intricate. Helpful for busy physicians are trustworthy expert recommendations
      which test to apply in which clinical situation.

PMID- 19105150
TI  - [Imaging for disorders in neurology and neurosurgery].
AB  - Imaging has become increasingly important for diagnosis and treatment of
      disorders in neurology and neurosurgery. Often, however, physicians are uncertain
      which imaging modality to chose for diagnosis and which techniques can be used to
      help for treatment. To answer a specific question clinicians have to rely on
      history and clinical findings. According to a cardinal clinical symptom or sign
      the imaging technique with the highest sensitivity and specificity for the given
      problem is chosen. In this review imaging techniques for the most common cardinal
      symptoms and signs in neurology and neurosurgery which need imaging for
      management are discussed.

PMID- 19105151
TI  - [Imaging of the chest].
AB  - Imaging of the chest made considerable progress over the past twenty years.
      Nevertheless, a chest X-ray remains one of the most informative and hence
      frequently used diagnostic procedures in daily medical practice. The choice of
      additional imaging techniques has to be based on pertinent differential
      diagnostic considerations. Basic knowledge of the various radiological techniques
      facilitates and improves the diagnostic process and a common terminology enhances
      the communication between the clinician and the radiologist. Modern radiological
      procedures are less invasive as compared to some historical procedures, are well
      tolerated by the patients and have a high sensitivity and specificity.

PMID- 19105152
TI  - [Imaging studies in the diagnosis of functional abdominal disorders].
AB  - Functional abdominal disorders are predominantly diagnosed on the basis of a
      thorough history and clinical examination. It is a challenge to clinicians to
      define the adequate place of imaging studies in order to rule out relevant
      organic disease. In functional dyspepsia, oesphago-gastroduodensoscopy and
      abdominal ultrasound are widely used as first line studies. Although irritable
      bowel syndrome is mainly diagnosed on clinical grounds, in patients over 50 years
      of age colonoscopy is almost mandatory, taking into account the importance of
      screening for colorectal cancer. In constipation-dominant irritable bowel
      syndrome, a marker study to determine colonic transit time will be helpful to
      differentiate this disorder from true slow transit constipation. Chronic or
      recurrent abdominal pain often warrants abdominal CT scan. Select cases are
      referred for laparoscopy.

PMID- 19105153
TI  - [Imaging for hepato-pancreatico-biliary diseases - a short review].
AB  - The purpose of this chapter is to give a practical and clinically-orientated
      overview over the best radiological imaging for the most frequent diseases of the
      hepato-pancreatico-biliary system. For this purpose the liver parenchyma, the
      biliary tree, the pancreas and the hepatic vasculature are dealt with separately.
      According to the presumed pathology, the most cost-saving and time-efficient
      radiological imaging can then be chosen.

PMID- 19105154
TI  - [Imaging of the kidney and the urinary tract].
AB  - Radiologic imaging is very important for urologic diagnostics. Acute flank pain
      is frequently caused by an obstructive ureteral stone which is diagnosed by
      native computed tomography (CT) or alternatively by intravenous urography (IVU).
      In suspicion of a parenchymal renal tumor a CT is performed. Tumors of the renal
      pelvis or the ureter are diagnosed by IVU followed by a retrograde pyelography to
      achieve a selective local wash-cytology. A CT or MRI of the abdomen are necessary
      for staging (local lymphnodes or systemic metastasis?) and to show also the local
      tumor extension. Exophytic and invasive processes of the bladder can be seen by
      CT or by ultrasound, but if a bladder tumor is suspected a cystoscopy is
      mandatory as primary diagnostic tool and can't be replaced by any imaging
      modalities. Cystography shows bladder injuries and serves together with a voiding
      image to identify vesicoureteral reflux. In strictures and injuries of the
      urethra a retro- and antegrade urethrography should be performed.

PMID- 19105155
TI  - [Imaging of arteries and veins].
AB  - For all arteries, which are easily accessible by ultrasound, a colordoppler
      ultrasound investigation is the first choice. The method is cost effective,
      precise, without radiation hazard and generates not only morphological, but also
      useful hemodynamic information. For the investigation of veins (Varicosis and
      thrombosis) colordoppler ultrasound has almost uniformly replaced phlebography as
      the method of choice.

PMID- 19105156
TI  - [Imaging procedures of the spine, bones, and joints].
AB  - Imaging procedures are an important diagnostic cornerstone for the examination
      and disorders of the musculoskeletal system. Thanks to the development made in
      the last 100 years, this kind of diagnosis has made an enormous progress and will
      continue to do so. Computer technology allows not only to improve and speed up
      the imaging process but also to make technically outstanding reconstructions
      which can be necessary for specific operative indications but provoke a
      development that does not meet the current requirements of cost effectiveness and
      expendiency. Thus, every user of this technique should be aware what he/she can
      expect from such an examination, what the outcome should be and how the results
      should be interpreted. We have to remember that imaging procedures alone do not
      make the diagnosis or define the type of therapy that should be performed, but
      have to be used together with other aspects like anamnesis and clinical
      examination. With such measures it is possible to make the majority of the
      diagnoses and begin the treatment. Complex imaging procedures are only reasonable
      and necessary if the therapy is not working anymore or if there are clear
      indications for systemic disorders like infections, malignancies or paralyses.

PMID- 19105157
TI  - [Imaging children - what is special?].
AB  - As children are not small adults, imaging evaluation needs to be adapted to their
      special features and diseases. This article discusses the imaging strategy for
      typical paediatric pathologies of the brain and skull, spinal cord and spine,
      chest, abdomen and musculoskeletal system. The most important consideration when
      imaging children is to optimise and reduce unnecessary or unnecessarily high
      radiation exposure. Whenever available, a radiation free imaging modality should
      be chosen. Ultrasound is considered the primary examination method in many
      circumstances and often reveals sufficient information. For advanced imaging of
      the abdomen, brain or musculoskeletal system, magnetic resonance imaging should
      be preferred over computed tomography (CT). Conventional radiographs remain the
      primary imaging modality for evaluation of the chest and bones. CT should be
      reserved for further evaluation of the lungs and airways, or for the emergent
      investigation of a major head injury or polytrauma. Every imaging study with
      ionising radiation requires a justifying medical indication. Radiography,
      fluoroscopy and CT should be performed on optimised equipment using special
      paediatric protocols in order to achieve a radiation exposure as low as possible.

PMID- 19105159
TI  - [Psychopharmacological treatment and youth welfare].

PMID- 19105160
TI  - [Psychotropic drugs for children - a brief historical review].
AB  - Already in the ancient world psychiatric disorders of children have been
      reported. However, only in the last decades the effectiveness of specific
      psychotropic drugs for the affected children have been investigated
      systematically. Especially in Germany there has been a controversial discussion
      about the application of neuroleptics in child and adolescent psychiatry.
      Important aspects of psychopharmacological therapy in childhood and adolescents
      are illustrated and discussed.

PMID- 19105161
TI  - [Alternative agents used in ADHD].
AB  - Attention-deficit/hyperactivity disorder (ADHD) is, with a prevalence of 2% to
      6%, one of the most common neurobehavioral disorder affecting children and
      adolescents, persisting into adulthood. Comorbidity and psychosocial
      circumstances enter into the choice of intervention strategies. Several agents
      have been demonstrated effective in treating individuals with ADHD. Direct or
      indirect attenuation of dopamine and norepinephrine neurotransmission appears
      closely related to both the stimulant and nonstimulant medications efficacious in
      ADHD. However, important differences concerning efficacy and side effects exist
      both between and with the specific classes of agents like neuroleptics,
      antidepressants, antiepileptics, alpha-agonists, beta-blockers, buspiron, l-dopa,
      melatonin, pycnogenol, zinc, magnesium, polyunsaturated fatty acids, and
      homeopathy. Elucidating the various mechanisms of action of ADHD medications may
      lead to better choices in matching potential responses to the characteristics of
      individuals. We review the purported mechanism of action and available evidence
      for selected complementary and alternative medicine therapies for ADHD in
      childhood and adolescence.

PMID- 19105162
TI  - [Pharmacotherapy in bipolar disorders during childhood and adolescence].
AB  - OBJECTIVE: Bipolar disorders during childhood and adolescence are rare, but
      serious and highly recurrent disorders, often associated with negative outcome.
      Pharmacotherapy, including Lithium, other mood stabilizers and typical
      antipsychotic agents, is the first-line treatment in bipolar disorders and often
      necessary for many months or years. METHOD: A computerized medline-search
      (Pubmed) was made for prospective studies and reviews of bipolar disorder in this
      age-group published during the last 10 years, which were then reviewed for their
      relevance. RESULTS: Despite the widespread use of substances whose efficacy for
      adults is well-established, there is a substantial lack of empirical data
      regarding the efficacy and safety in the treatment of bipolar disorder in
      children and adolescents. Placebo-controlled studies are very rare, and the
      interpretation of the existing data is complicated by the diagnostic controversy
      about bipolar disorder in children. Side-effects are more common in children and
      adolescents than in adults. CONCLUSIONS: Combination therapy may be favoured in
      cases of severe and psychotic bipolar disorder. Needed are more placebo
      controlled studies and long-term studies on the efficacy and safety of mood
      stabilizers and atypical antipsychotic agents in the treatment of children and
      adolescents with bipolar disorder.

PMID- 19105163
TI  - [Impact factors and publication time spans of child and adolescent psychiatry
      journals].
AB  - OBJECTIVE: The impact factor (IF) of a scientific journal plays a central role in
      a scientist's decision where to publish his or her research results. Authors also
      show interest in the publication time span (time span between the submission and
      the online or print publication of a article). This paper presents an overview of
      the IF and editorial time spans of German and international child and adolescent
      psychiatric journals and compares them to those of journals of adult psychiatry.
      METHOD: The authors first conducted a data bank search at the Journal Citation
      Reports, concerning IF and IF-development for key journals of child and
      adolescent psychiatry from 2002-2007. They then manually analyzed pertinent child
      and adolescent journals regarding the time span for publications in the year
      2007. RESULTS: To date, nine child and adolescent psychiatric journals exist,
      whereof eight present with an impact factor. The IF ranges from 0.419 (praxis der
      Kinderpsychologie und Kinderpsychiatrie) to 4.655 (Journal of the American
      Academy of Child and Adolescent Psychiatry). The editorial handling time ranges
      between 5.4 and 13.2 months. CONCLUSION: Even though this academic discipline is
      "small", child and adolescent psychiatry disposes of international journals
      presenting with competitive IFs. Both German journals show a low IF. The
      editorial handling times were reasonable, but could be further reduced by
      offering prior online publication.

PMID- 19105164
TI  - [Need for child welfare care after inpatient child and adolescent psychiatric
      treatment].
AB  - OBJECT: New research confirms the high prevalence of mental disorders among
      children and adolescents in the setting of child welfare services. This study
      examines the need for child welfare care subsequent to inpatient child and
      adolescent psychiatric treatment. METHOD: We analysed the basic documentation of
      the patients in the years 2001 to 2005 in the Department of Child and Adolescent
      Psychiatry, Wurzburg, with regard to the indication of need for or the
      implementation of child welfare services. Moreover, we examined which factors
      will vary the risk of need for child welfare services. RESULTS: Nearly 50% of all
      inpatient children and adolescents had an indicated need for child welfare
      service; these services, however, were directly implemented for only half this
      number. And of those, more than every third procedure involved residential care.
      Early onset of the mental disorder, abnormal situation of the parents, external
      mental disorder, and a high rate of psychosocial risk factors increase the risk
      for child welfare services.

PMID- 19105165
TI  - [ADHD among boys in childhood: quality of life and parenting behavior].
AB  - Recent studies suggest that psychological adjustment is impaired in children with
      attention-deficit/hyperactivity disorder (ADHD). Additionally, psychosocial
      functioning of significant others is also affected. The present study examined
      the quality of life (QoL) in two age groups of children with ADHD (8-9 vs. 10-11
      years) compared to healthy controls matched by age, verbal intelligence, and
      education level. Furthermore, the QoL and the parenting behavior of mothers were
      investigated. In total, N = 58 mothers rated their own QoL and that of their
      children. In addition, they made judgements about their own parenting behavior.
      Age effects did not reach statistical significance, but QoL was impaired in
      children with ADHD when compared to healthy controls. Moreover, the mental and
      the physical well-being of mothers of a child with ADHD were negatively affected.
      Finally, a more negative parenting behavior of mothers of a child with ADHD was
      found compared to parents of a healthy child. These results underline the need
      for family-oriented interventions in ADHD that take into account the psychosocial
      adjustments of significant others.

PMID- 19105168
TI  - Practical imidazole-based phosphine ligands for selective palladium-catalyzed
      hydroxylation of aryl halides.

PMID- 19105169
TI  - Analysis of cotton (Gossypium hirsutum) root proteomes during a compatible
      interaction with the black root rot fungus Thielaviopsis basicola.
AB  - A proteomic approach was used to uncover the inducible molecular defense
      mechanism of cotton root occurring during the compatible interaction with
      Thielaviopsis basicola. Microscopic observation of cotton root inoculated with a
      suspension of conidia showed that this necrotrophic hemibiotroph fungus interacts
      with the plant and completes its life cycle in our experimental system. 2-DE
      analysis of root extracts taken after 1, 3, 5, and 7 days postinoculation and
      cluster analysis of the protein expression levels showed four major profiles
      (constant, upregulated, one slightly downregulated, and one dramatically
      downregulated). Spots significantly (p<0.05) upregulated were analyzed by LC
      MS/MS and identified using MASCOT MS/MS ion search software and associated
      databases. These proteins included defense and stress related proteins, such as
      pathogenesis-related proteins and proteins likely to be involved in the oxidative
      burst, sugar, and nitrogen metabolism as well as amino acid and isoprenoid
      synthesis. While many of the identified proteins are common components of the
      defense response of most plants, a proteasome subunit and a protein reported to
      be induced only in cotton root following Meloidogyne incognita infection were
      also identified.

PMID- 19105170
TI  - Quantitative iTRAQ proteome and comparative transcriptome analysis of elicitor
      induced Norway spruce (Picea abies) cells reveals elements of calcium signaling
      in the early conifer defense response.
AB  - Long-lived conifer trees depend on both constitutive and induced defenses for
      resistance against a myriad of potential pathogens and herbivores. In species of
      spruce (Picea spp.), several of the late events of pathogen-, insect-, or
      elicitor-induced defense responses have previously been characterized at the
      anatomical, biochemical, transcriptome, and proteome levels in stems and needles.
      However, accurately measuring the early events of induced cellular responses in a
      conifer is technically challenging due to limitations in the precise timing of
      induction and tissue sampling from intact trees following insect or fungal
      treatment. In the present study, we used the advantages of Norway spruce (Picea
      abies) cell suspensions combined with chitosan elicitation to investigate the
      early proteome response in a conifer. A combination of iTRAQ labeling and a new
      design of iterative sample analysis employing data-dependent exclusion lists were
      used for proteome analysis. This approach improved the coverage of the spruce
      proteome beyond that achieved in any prior study in a conifer system. Comparison
      of elicitor-induced proteome and transcriptome responses in Norway spruce cells
      consistently identified features associated with calcium-mediated signaling and
      response to oxidative stress that have not previously been observed in the
      response of intact trees to fungal attack.

PMID- 19105171
TI  - A label-free internal standard method for the differential analysis of bioactive
      lupin proteins using nano HPLC-Chip coupled with Ion Trap mass spectrometry.
AB  - Quantitative proteomics based on MS is useful for pointing out the differences in
      some food proteomes relevant to human nutrition. Stable isotope label-free (SIF)
      techniques are suitable for comparing an unlimited number of samples by the use
      of relatively simple experimental workflows. We have developed an internal
      standard label-free method based on the intensities of peptide precursor ions
      from MS/MS spectra, collected in data dependent runs, for the simultaneous
      qualitative characterization and relative quantification of storage proteins of
      Lupinus albus seeds in protein extracts of four lupin cultivars (cv Adam, Ares,
      Lucky, Multitalia). The use of an innovative microfluidic system, the HPLC-Chip,
      coupled with a classical IT mass spectrometer, has allowed a complete qualitative
      characterization of all proteins. In particular, the homology search mode has
      permitted to identify single amino acid substitutions in the sequences of
      vicilins (beta-conglutin precursor and vicilin-like protein). The MS/MS
      sequencing of substituted peptides confirms the high heterogeneity of vicilins
      according to the peculiar characteristics of the vicilin-encoding gene family.
      Two suitable bioinformatics parameters were optimized for the differential
      analyses of the main bioactive proteins: the "normalized protein average of
      common reproducible peptides" (N-ACRP) for gamma-conglutin, which is a
      homogeneous protein, and the "normalized protein mean peptide spectral intensity"
      (N-MEAN) for the highly heterogenous class of the vicilins.

PMID- 19105172
TI  - A comprehensive analysis of Trypanosoma brucei mitochondrial proteome.
AB  - The composition of the large, single, mitochondrion (mt) of Trypanosoma brucei
      was characterized by MS (2-D LC-MS/MS and gel-LC-MS/MS) analyses. A total of 2897
      proteins representing a substantial proportion of procyclic form cellular
      proteome were identified, which confirmed the validity of the vast majority of
      gene predictions. The data also showed that the genes annotated as hypothetical
      (species specific) were overpredicted and that virtually all genes annotated as
      hypothetical, unlikely are not expressed. By comparing the MS data with genome
      sequence, 40 genes were identified that were not previously predicted. The data
      are placed in a publicly available web-based database (www.TrypsProteome.org).
      The total mitochondrial proteome is estimated at 1008 proteins, with 401, 196,
      and 283 assigned to the mt with high, moderate, and lower confidence,
      respectively. The remaining mitochondrial proteins were estimated by statistical
      methods although individual assignments could not be made. The identified
      proteins have predicted roles in macromolecular, metabolic, energy generating,
      and transport processes providing a comprehensive profile of the protein content
      and function of the T. brucei mt.

PMID- 19105173
TI  - A simple preparation of pyridine-derived N-heterocyclic carbenes and their
      transformation into bridging ligands by orthometalation.

PMID- 19105174
TI  - A hybrid organic/inorganic benzene.

PMID- 19105175
TI  - Combinatorial mutasynthesis of scrambled beauvericins, cyclooligomer depsipeptide
      cell migration inhibitors from Beauveria bassiana.
AB  - Fungal cyclooligomer depsipeptides such as beauvericin, bassianolide, and
      enniatins display antibiotic, antifungal, insecticidal, broad-spectrum cancer
      cell antiproliferative, and cell migration inhibitory activities. We have
      identified a gene encoding a novel enzyme, ketoisovalerate reductase (KIVR),
      which is the sole provider of D-hydroxyisovalerate (D-Hiv), a common precursor
      for cyclooligomer depsipeptide biosynthesis in Beauveria bassiana. KIVR and
      related hypothetical oxidoreductases encoded in fungal genomes are similar to
      ketopantoate reductases but not to D-hydroxycarboxylate dehydrogenases. We
      demonstrate that a KIVR knockout B. bassiana strain can be used for the efficient
      mutasynthesis of unnatural beauvericin congeners. Simultaneous feeding of
      precursor analogues enabled the combinatorial mutasynthesis of scrambled
      beauvericins, some assembled entirely from unnatural precursors. The effects of
      the introduced structural changes on the antiproliferative and cell migration
      inhibitory activities of these analogues were evaluated.

PMID- 19105176
TI  - Iodothyronamines are oxidatively deaminated to iodothyroacetic acids in vivo.
AB  - 3-Iodothyronamine (T(1)AM) and 3,3',5-triiodothyroacetic acid (Triac) are
      bioactive metabolites of the hormone thyroxine (T(4)). In the present study, the
      ability of T(1)AM and 3,3',5-triiodothyronamine (T(3)AM) to be metabolized to 3
      iodothyroacetic acid (TA(1)) and Triac, respectively, was investigated. Both
      T(1)AM and T(3)AM were converted to their respective iodinated thyroacetic acid
      analogues in both cell and tissue extracts. This conversion could be
      significantly inhibited with the monamine oxidase (MAO) and semicarbazide
      sensitive amine oxidase (SSAO) inhibitor iproniazid. TA(1) was found to be
      present in trace quantities in human serum and in substantial levels in serum
      from T(1)AM-treated rats. These results demonstrate that iodothyronamines are
      substrates for amine oxidases and that this metabolism may be the source of the
      corresponding endogenous arylacetic acid products Triac and TA(1).

PMID- 19105178
TI  - Investigating sample pooling strategies for DIGE experiments to address
      biological variability.
AB  - If biological questions are to be answered using quantitative proteomics, it is
      essential to design experiments which have sufficient power to be able to detect
      changes in expression. Sample subpooling is a strategy that can be used to reduce
      the variance but still allow studies to encompass biological variation.
      Underlying sample pooling strategies is the biological averaging assumption that
      the measurements taken on the pool are equal to the average of the measurements
      taken on the individuals. This study finds no evidence of a systematic bias
      triggered by sample pooling for DIGE and that pooling can be useful in reducing
      biological variation. For the first time in quantitative proteomics, the two
      sources of variance were decoupled and it was found that technical variance
      predominates for mouse brain, while biological variance predominates for human
      brain. A power analysis found that as the number of individuals pooled increased,
      then the number of replicates needed declined but the number of biological
      samples increased. Repeat measures of biological samples decreased the numbers of
      samples required but increased the number of gels needed. An example cost benefit
      analysis demonstrates how researchers can optimise their experiments while taking
      into account the available resources.

PMID- 19105177
TI  - Investigations into viomycin biosynthesis by using heterologous production in
      Streptomyces lividans.
AB  - Viomycin and capreomycin are members of the tuberactinomycin family of
      antituberculosis drugs. As with many antibacterial drugs, resistance to the
      tuberactinomycins is problematic in treating tuberculosis; this makes the
      development of new derivatives of these antibiotics to combat this resistance of
      utmost importance. To take steps towards developing new derivatives of this
      family of antibiotics, we have focused our efforts on understanding how these
      antibiotics are biosynthesized by the producing bacteria so that metabolic
      engineering of these pathways can be used to generate desired derivatives. Here
      we present the heterologous production of viomycin in Streptomyces lividans 1326
      and the use of targeted-gene deletion as a mechanism for investigating viomycin
      biosynthesis as well as the generation of viomycin derivatives. Deletion of vioQ
      resulted in nonhydroxylated derivatives of viomycin, while strains lacking vioP
      failed to acylate the cyclic pentapeptide core of viomycin with beta-lysine.
      Surprisingly, strains lacking vioL produced derivatives that had the carbamoyl
      group of viomycin replaced by an acetyl group. Additionally, the acetylated
      viomycin derivatives were produced at very low levels. These two observations
      suggested that the carbamoyl group of the cyclic pentapeptide core of viomycin
      was introduced at an earlier step in the biosynthetic pathway than previously
      proposed. We present biochemical evidence that the carbamoyl group is added to
      the beta-amino group of L-2,3-diaminopropionate prior to incorporation of this
      amino acid by the nonribosomal peptide synthetases that form the cyclic
      pentapeptide cores of both viomycin and capreomycin.

PMID- 19105179
TI  - Dissecting the human plasma proteome and inflammatory response biomarkers.
AB  - A central focus of clinical proteomics is to search for biomarkers in plasma for
      diagnostic and therapeutic use. We studied a set of plasma proteins accessed from
      the Healthy Human Individual's Integrated Plasma Proteome (HIP(2)) database, a
      larger set of curated human proteins, and a subset of inflammatory proteins, for
      overlap with sets of known protein biomarkers, drug targets, and secreted
      proteins. Most inflammatory proteins were found to occur in plasma, and over
      three times the level of biomarkers were found in inflammatory plasma proteins
      and their interacting protein neighbors compared to the sets of plasma and
      curated human proteins. Percentage overlaps with Gene Ontology terms were similar
      between the curated human set and plasma protein set, yet the set of inflammatory
      plasma proteins had a distinct ontology-based profile. Most of the major hub
      proteins within protein-protein interaction networks of tissue-specific sets of
      inflammatory proteins were found to occur in disease pathways. The present study
      presents a systematic approach for profiling a plasma subproteome's relationship
      to both its potential range of clinical application and its overlap with complex
      disease.

PMID- 19105180
TI  - Proteomics data collection--4th ProDaC workshop 15 August 2008, Amsterdam, The
      Netherlands.
AB  - ProDaC (Proteomics Data Collection), a "Coordination Action" within the 6(th) EU
      framework programme, was created to support the collection, distribution and
      public availability of data from proteomics experiments. Within the consortium
      standards are created and maintained enabling an extensive data collection within
      the proteomics community. Important elements of ProDaC are workshops held twice a
      year to allow communication between the ProDaC partners and to report the ongoing
      progress. The most recent assembly was the 4(th) ProDaC workshop on August
      15(th), 2008, in Amsterdam, The Netherlands. It took place directly before the
      7(th) HUPO Annual World Congress (Human Proteome Organisation). Work package
      coordinators and partners presented the progress achieved since the last meeting.
      Additionally, an EU official presented funding opportunities for proteomics in
      the next EU framework programme and five external speakers presented talks about
      their work in relation to ProDaC.

PMID- 19105181
TI  - 5th BSPR-EBI meeting, proteomics: from Technology to New Biology 8-10 July 2008,
      Wellcome Trust Conference Centre, Hinxton, Cambridge, UK.
AB  - This paper reports on the 5(th) joint British Society for Proteome Research
      (BSPR) and European Bioinformatics Institute (EBI) meeting which took place at
      the Wellcome Trust Conference Centre, Cambridge, UK, from the 8(th) to 10(th)
      July, 2008. As in previous years, the meeting attracted leading experts in the
      field who presented the latest cutting edge in proteomics. The meeting was
      entitled "Proteomics: From Technology to New Biology" taking into account the
      major transition proteomics has undergone in the past few years. In particular,
      the use of multiple reaction monitoring (MRM)-based targeted experiments for
      absolute quantification and validation of proteins was the hot topic of the
      meeting. Attended by some 250 delegates, the conference was extremely well
      organised and provided a great opportunity for discussion and initiation of new
      collaborations.

PMID- 19105182
TI  - Enhancing the quantum properties of manganese-lanthanide single-molecule magnets:
      observation of quantum tunneling steps in the hysteresis loops of a {Mn12Gd}
      cluster.

PMID- 19105183
TI  - Identification of in vitro phosphorylation sites in the Arabidopsis thaliana
      somatic embryogenesis receptor-like kinases.
AB  - The Arabidopsis thaliana somatic embryogenesis receptor-like kinase (SERK) family
      consists of five leucine-rich repeat receptor-like kinases (LRR-RLKs) with
      diverse functions such as brassinosteroid insensitive 1 (BRI1)-mediated
      brassinosteroid perception, development and innate immunity. The
      autophosphorylation activity of the kinase domains of the five SERK proteins was
      compared and the phosphorylated residues were identified by LC-MS/MS. Differences
      in autophosphorylation that ranged from high activity of SERK1, intermediate
      activities for SERK2 and SERK3 to low activity for SERK5 were noted. In the SERK1
      kinase the C-terminally located residue Ser-562 controls full autophosphorylation
      activity. Activation loop phosphorylation, including that of residue Thr-462
      previously shown to be required for SERK1 kinase activity, was not affected. In
      vivo SERK1 phosphorylation was induced by brassinosteroids. Immunoprecipitation
      of CFP-tagged SERK1 from plant extracts followed by MS/MS identified Ser-303, Thr
      337, Thr-459, Thr-462, Thr-463, Thr-468, and Ser-612 or Thr-613 or Tyr-614 as in
      vivo phosphorylation sites of SERK1. Transphosphorylation of SERK1 by the kinase
      domain of the main brassinosteroid receptor BRI1 occurred only on Ser-299 and Thr
      462. This suggests both intra- and intermolecular control of SERK1 kinase
      activity. Conversely, BRI1 was transphosphorylated by the kinase domain of SERK1
      on Ser-887. BRI1 kinase activity was not required for interaction with the SERK1
      receptor in a pull down assay.

PMID- 19105184
TI  - Chromosomal and proteome analysis of a new T24-based cell line model for
      aggressive bladder cancer.
AB  - Cell line models aid in understanding cancer aggressiveness. The aim of this
      study was the establishment of a metastatic variant (T24M) of the T24 bladder
      cancer cell line and its initial characterization at chromosomal and proteomic
      levels. T24M were spontaneously developed in mice from T24 cells, following
      cycles of subcutaneous injections and culture in vitro. Transwell migration
      assays and injections in mice revealed increased migration and tumorigenic
      properties of T24M compared to the T24 cells. Cytogenetic analysis demonstrated
      that T24M retained several karyotypic characteristics of the parental cells and
      also acquired novel chromosomal aberrations related to aggressive bladder cancer.
      Proteomic analysis of the T24 and T24M cells by 2-DE and MS led to the generation
      of their 2-DE proteomic map and revealed differences in multiple proteins. These
      include proteases of the lysosomal and proteasome degradation pathways,
      mitochondrial and cytoskeletal proteins. The 2-DE findings were confirmed by
      immunoblotting of cell lysates and immunohistochemistry of bladder cancer tissue
      sections for cathepsin D and activity assays for proteasome. Collectively, our
      results suggest that the T24M cells reflect many known chromosomal and proteomic
      aberrations encountered in aggressive bladder cancers but also provide access to
      novel findings with potentially clinical applications.

PMID- 19105185
TI  - Fertility defects revealing germline biallelic nonsense NBN mutations.
AB  - Biallelic mutations in the NBN/NBS1 gene are the cause of Nijmegen breakage
      syndrome (NBS), a severe pediatric disease characterized by dysmorphy with a bird
      like face, microcephaly, growth retardation, immune deficiency, and proneness to
      cancer. We here report two adult siblings that are compound heterozygotes for two
      previously unreported NBN nonsense mutations. These patients presented with the
      unique clinical symptom of fertility defects. Contrasting with the absence of any
      developmental abnormality, biological analyses revealed defects similar to those
      observed in NBS patients, including chromosomal instability, cellular
      hyperradiosensitivity and checkpoint defects as measured by radioresistant DNA
      synthesis (RDS). NBN mutations should thus be considered a new cause of
      infertility, and should be searched for if associated with the biological
      abnormalities of NBS.

PMID- 19105187
TI  - MedRefSNP: a database of medically investigated SNPs.
AB  - Genetic association studies and linkage analyses using single nucleotide
      polymorphisms (SNPs) are rapidly increasing in number, and the results are
      important for evaluating the utility of SNPs in the biomedical sciences. Although
      many SNP databases have been established, there is no database focusing on
      published SNPs, where the research results of scientific investigations are
      available. To enhance the utilization of such SNP data, we have developed the
      MedRefSNP database (http://www.medclue.com/medrefsnp) to provide integrated
      information about SNPs collected from the PubMed and OMIM databases. The RefSNP
      identifiers are automatically identified and are linked to various information
      sources such as the dbSNP, the HapMap database, the Entrez Gene database, the
      UCSC genome browser, the CGAP Pathway Searcher, and genetic association
      databases. And, each SNP is checked to determine whether the PolyDoms, SNPs3D or
      PolyPhen databases predicts that the SNP affects the phenotype of the protein
      encoded by the gene carrying the SNP. Also, neighboring SNPs showing strong
      linkage disequilibrium (LD) with published SNPs are included, using HapMap data.
      Currently, 36199 unique SNPs (including 31368 neighboring SNPs) collected from
      25906 PubMed abstracts and 590 OMIM records are stored along with 2491 human
      genes related to 466 molecular pathways. The MedRefSNP database will help
      researchers to review previously investigated results more efficiently, and will
      expand knowledge by using the genomic and functional contexts of the SNPs.

PMID- 19105186
TI  - Identification of novel mutations and sequence variation in the Zellweger
      syndrome spectrum of peroxisome biogenesis disorders.
AB  - Peroxisome biogenesis disorders (PBD) are a heterogeneous group of autosomal
      recessive neurodegenerative disorders that affect multiple organ systems.
      Approximately 80% of PBD patients are classified in the Zellweger syndrome
      spectrum (PBD-ZSS). Mutations in the PEX1, PEX6, PEX10, PEX12, or PEX26 genes are
      found in approximately 90% of PBD-ZSS patients. Here, we sequenced the coding
      regions and splice junctions of these five genes in 58 PBD-ZSS cases previously
      subjected to targeted sequencing of a limited number of PEX gene exons. In our
      cohort, 71 unique sequence variants were identified, including 18 novel mutations
      predicted to disrupt protein function and 2 novel silent variants. We identified
      4 patients who had two deleterious mutations in one PEX gene and a third
      deleterious mutation in a second PEX gene. For two such patients, we conducted
      cell fusion complementation analyses to identify the defective gene responsible
      for aberrant peroxisome assembly. Overall, we provide empirical data to estimate
      the relative fraction of disease-causing alleles that occur in the coding and
      splice junction sequences of these five PEX genes and the frequency of cases
      where mutations occur in multiple PEX genes. This information is beneficial for
      efforts aimed at establishing rapid and sensitive clinical diagnostics for PBD
      ZSS patients and interpreting the results from these genetic tests.

PMID- 19105188
TI  - The proportion of mutations predicted to have a deleterious effect differs
      between gain and loss of function genes in neurodegenerative disease.
AB  - As more studies are turning to bioinformatic prediction programs to assess the
      potential impact of amino acid substitutions, it is relevant to evaluate the
      prediction results these programs give in genes that have been well-characterized
      for Mendelian diseases. Eight genes responsible for neurodegenerative disease
      with many identified mutations were sub-grouped into those that either have a
      gain or loss of function disease mechanism. Three prediction programs, PolyPhen,
      Panther and SIFT, were queried for the reported missense mutations. The mean
      percent of benign mutations was significantly higher in gain of function genes
      using the PolyPhen program (38% versus 21%, p=0.007). The probability that a gain
      of function mutation was predicted to have a damaging role was also significantly
      less using the Panther program (p=4.86x10(-12)). In contrast, there was no
      difference between gain and loss of function gene when the SIFT program was used.
      However, the most accurate distinction between gain and loss of function genes
      could be obtained when considering the mutations for which all three programs
      predicted the same result. Further, stratification of SOD1 mutations indicated
      that only the PolyPhen program could distinguish mutations that impaired
      enzymatic activity of SOD1 from those with near wildtype activity. The profile of
      benign and damaging changes from these genes will aid in the interpretation of
      bioinformatic prediction program results from missense mutations identified in
      novel genes.

PMID- 19105189
TI  - How much mutant protein is needed to cause a protein aggregate myopathy in vivo?
      Lessons from an exceptional desminopathy.
AB  - Myofibrillar myopathies are caused by mutations in desmin, alphaB-crystallin,
      myotilin, ZASP, and filamin C genes. Since the vast majority of myofibrillar
      myopathy causing mutations are heterozygous single amino acid substitutions or
      small in-frame deletions, the pathogenic role of mutant versus wild-type protein
      cannot be assessed in human skeletal muscle by standard immunodetection
      techniques. We report on an exceptional desminopathy due to a heterozygous
      c.735G>C mutation. Immunoblotting detected full-length 53 kDa desmin and a
      truncated 50 kDa variant in skeletal muscle from three affected patients of two
      different families. RT-PCR identified three desmin mRNA species encoding for wild
      type and two mutant proteins, p.Glu245Asp and p.Asp214_Glu245del. Since previous
      functional studies on the p.Glu245Asp mutant showed biological properties
      identical to wild-type desmin, the truncated p.Asp214_Glu245del desmin is the
      disease-causing mutant. Semiquantitative RT-PCR established a fraction of the
      truncated desmin mRNA species in a range from 24% to 37%. Initial quantification
      of corresponding desmin proteins in the muscle biopsy of the index patient of one
      family indicated a fraction of only 10% of the truncated species. However, serial
      analyses of different sections from each muscle biopsy revealed a high intra- and
      interindividual variability of the truncated desmin protein level within a range
      from 5% to 43%. Desmin assembly studies in vitro have established clear-cut
      pathogenic ratios of mutant versus wild-type proteins. However, our findings
      point out a far more complex situation in human skeletal muscle. The
      heterogeneously distributed mutation load within and between individual
      specimens, which reflects local differences in the expression and/or turnover of
      the mutant protein in different areas containing multiple myonuclear domains,
      renders it impossible to define an exact pathogenic threshold of a specific
      mutant in vivo.

PMID- 19105190
TI  - Screening of ARHSP-TCC patients expands the spectrum of SPG11 mutations and
      includes a large scale gene deletion.
AB  - Autosomal recessive spastic paraplegia with thinning of corpus callosum (ARHSP
      TCC) is a complex form of HSP initially described in Japan but subsequently
      reported to have a worldwide distribution with a particular high frequency in
      multiple families from the Mediterranean basin. We recently showed that ARHSP-TCC
      is commonly associated with mutations in SPG11/KIAA1840 on chromosome 15q. We
      have now screened a collection of new patients mainly originating from Italy and
      Brazil, in order to further ascertain the spectrum of mutations in SPG11, enlarge
      the ethnic origin of SPG11 patients, determine the relative frequency at the
      level of single Countries (i.e., Italy), and establish whether there is one or
      more common mutation. In 25 index cases we identified 32 mutations; 22 are novel,
      including 9 nonsense, 3 small deletions, 4 insertions, 1 in/del, 1 small
      duplication, 1 missense, 2 splice-site, and for the first time a large genomic
      rearrangement. This brings the total number of SPG11 mutated patients in the
      SPATAX collection to 111 cases in 44 families and in 17 isolated cases, from 16
      Countries, all assessed using homogeneous clinical criteria. While expanding the
      spectrum of mutations in SPG11, this larger series also corroborated the notion
      that even within apparently homogeneous population a molecular diagnosis cannot
      be achieved without full gene sequencing.

PMID- 19105191
TI  - Reactions of diazo compounds with alkenes catalysed by [RuCl(cod)(Cp)]: effect of
      the substituents in the formation of cyclopropanation or metathesis products.
AB  - The reaction of diazo compounds with alkenes catalysed by complex [RuCl(cod)(Cp)]
      (cod = 1,5-cyclooctadiene, Cp = cyclopentadienyl) has been studied. The catalytic
      cycle involves in the first step the decomposition of the diazo derivative to
      afford the reactive [RuCl(Cp){=C(R(1))R(2)}] intermediate and a mechanism is
      proposed for this step based on a kinetic study of the simple coupling reaction
      of ethyl diazoacetate. The evolution of the Ru-carbene intermediate in the
      presence of alkenes depends on the nature of the substituents at both the diazo
      N(2)=C(R(1))R(2) (R(1), R(2) = Ph, H; Ph, CO(2)Me; Ph, Ph; C(R(1))R(2) =
      fluorene) and the olefin substrates R(3)(H)C=C(H)R(4) (R(3), R(4) = CO(2)Et,
      CO(2)Et; Ph, Ph; Ph, Me; Ph, H; Me, Br; Me, CN; Ph, CN; H, CN; CN, CN). A
      remarkable reactivity of the complex was recorded, especially towards unstable
      aryldiazo compounds and electron-poor olefins. The results obtained indicate that
      either cyclopropanation or metathesis products can be formed: the first products
      are favoured by the presence of a cyano substituent at the double bond and the
      second ones by a phenyl.

PMID- 19105192
TI  - Energetic silver salts with 5-aminotetrazole ligands.
AB  - Methylation of 5-amino-1H-tetrazole (1) gives 1-methyl-5-amino-1H-tetrazole (2)
      and 2-methyl-5-amino-1H-tetrazole (3). A new family of energetic silver complexes
      based on ligands 1, 2 and 3 with perchlorate and nitrate anions (10-15) were
      synthesized and characterized by using IR, Raman, and NMR ((1)H, (13)C, (14)N,
      and (35)Cl NMR) spectroscopy, elemental analysis, and mass spectrometry. The
      crystal structures of the compounds were determined where possible and reveal
      interesting structural details that are discussed herein. Additionally,
      differential scanning calorimetry was used to assess the thermal stability of the
      new salts, which showed excellent thermal stabilities at temperatures up to and
      above 225 degrees C. Standard tests were also used to assess the sensitivity of
      the materials towards impact and friction. All the silver complexes showed
      increased sensitivity values in comparison with analogous protonated 5-amino-1H
      tetrazolium perchlorate and nitrate salts. Some of these materials have
      sensitivity values that are comparable to commonly used primary explosives and
      all of them either deflagrate (12-14) or detonate loudly (10 and 11) on contact
      with an open flame. Lastly, nitrate salt 11 is easily initiated by thermal shock.
      It shows reasonably low sensitivity in comparison with other silver salts (e.g.,
      silver azide or silver fulminate), which makes handling it much less hazardous.
      Compound 11 also has good thermal stability, decomposing at approximately 300
      degrees C, and shows interesting properties as a more environmentally benign
      alternative to lead(II) diazide in initiation devices for civil and military
      applications.

PMID- 19105193
TI  - Structural and magnetic insights into the trinuclear ferrocenophane and
      unexpected hydrido inverse crown products of alkali-metal-mediated
      manganation(II) of ferrocene.
AB  - With the aim of introducing the diisopropylamide [NiPr(2)](-) ligand to alkali
      metal-mediated manganation (AMMMn) chemistry, the temperature-dependent reactions
      of a 1:1:3 mixture of butylsodium, bis(trimethylsilylmethyl)manganese(II), and
      diisopropylamine with ferrocene in hexane/toluene have been investigated.
      Performed at reflux temperature, the reaction affords the surprising, ferrocene
      free, hydrido product [Na(2)Mn(2) (mu-H)(2){N(iPr)(2)}(4)]2 toluene (1), the
      first Mn hydrido inverse crown complex. Repeating the reaction rationally,
      excluding ferrocene, produces 1 in an isolated crystalline yield of 62 %. At
      lower temperatures, the same bimetallic amide mixture leads to the manganation of
      ferrocene to generate the first trimanganese, trinuclear ferrocenophane,
      [{Fe(C(5)H(4))(2)}(3){Mn(3)Na(2)(NiPr(2))(2) (HNiPr(2))(2)}] (2) in an isolated
      crystalline yield of 81 %. Both 1 and 2 have been characterised by X-ray
      crystallographic studies. The magnetic properties of paramagnetic 1 and 2 have
      also been examined by variable-temperature magnetisation measurements on powdered
      samples. For 1, the room-temperature value for chiT is 3.45 cm(3) K mol(-1), and
      on lowering the temperature a strong antiferromagnetic coupling between the two
      Mn ions is observed. For 2, the room-temperature value for chiT is 4.06 cm(3) K
      mol(-1), which is significantly lower than the expected value for three isolated
      paramagnetic Mn(II) ions.

PMID- 19105194
TI  - Functionally rigid and degenerate molecular shuttles.
AB  - The preparation and dynamic behavior of two functionally rigid and degenerate
      [2]rotaxanes (14 PF(6) and 24 PF(6)) in which a pi-electron deficient
      tetracationic cyclophane, cyclobis(paraquat-p-phenylene) (CBPQT(4+)) ring,
      shuttles back and forth between two pi-electron-rich naphthalene (NP) stations by
      making the passage along an ethynyl-phenylene-(PH)-ethynyl or butadiyne rod, are
      described. The [2]rotaxanes were synthesized by using the clipping approach to
      template-directed synthesis, and were characterized by NMR spectroscopic and mass
      spectrometric analyses. (1)H NMR spectra of both [2]rotaxanes show evidence for
      the formation of mechanically interlocked structures, resulting in the upfield
      shifts of the resonances for key protons on the dumbbell-shaped components. In
      particular, the signals for the peri protons on the NP units in the dumbbell
      shaped components experienced significant upfield shifts at low temperatures,
      just as has been observed in the flexible [2]rotaxanes. Interestingly, the
      resonances for the same protons did not exhibit a significant upfield shift at
      298 K, but rather only a modest shift. This phenomenon arises from the much
      reduced binding of the ethynyl-NP unit compared to the 1,5-dioxy-NP unit. This
      effect, in turn, increases the shuttling rate when compared to the 1,5-dioxy-NP
      based rotaxane systems investigated previously. The kinetic and thermodynamic
      data of the shuttling behavior of the CBPQT(4+) ring between the NP units were
      obtained by variable-temperature NMR spectroscopy and using the coalescence
      method to calculate the free energies of activation (DeltaG(c) ( not equal)) of
      9.6 and 10.3 kcal mol(-1) for 14 PF(6) and 24 PF(6), respectively, probed by
      using the rotaxane's alpha-bipyridinium protons. The solid-state structure of the
      free dumbbell-shaped compound (3) shows the fully rigid ethynyl-PH-ethynyl linker
      with a length (8.1 A) twice as long as that (3.8 A) of the butadiyne linker. Full
      atomistic simulations were carried out with the DREIDING force field (FF) to
      probe the degenerate molecular shuttling processes, and afforded shuttling energy
      barriers (DeltaG( not equal)=10.4 kcal mol(-1) for 14 PF(6) and 24 PF(6)) that
      are in good agreement with the experimental values (DeltaG(c) ( not equal)=9.6
      and 10.3 kcal mol(-1) for 14 PF(6) and 24 PF(6), respectively, probed by using
      their alpha-bipyridinium protons).

PMID- 19105195
TI  - Total synthesis of phosphatidylinositol dimannoside: a cell-envelope component of
      Mycobacterium tuberculosis.

PMID- 19105196
TI  - Intracellular sAPP retention in response to Abeta is mapped to cytoskeleton
      associated structures.
AB  - Amyloid beta (Abeta) contributes to neurodegeneration in Alzheimer's disease and
      provides a close association between molecular events and pathology, although the
      underlying molecular mechanisms are unclear. In the work described here, Abeta
      did not induce amyloid precursor protein (APP) expression, but APP
      processing/trafficking was markedly affected. In COS-7 cells, Abeta provokes
      retention of intracellular sAPPalpha (isAPPalpha). Intracellular holo-APP levels
      remain unchanged, and extracellular total sAPP increases, although extracellular
      sAPPalpha alone was not altered significantly. In primary neuronal cultures and
      PC12 cells, isAPP also increased, but this was mirrored by a decrease in
      extracellular total sAPP. The isAPP retention was particularly associated with
      the cytoskeletal fraction. The retention "per se" occurred in vesicular-like
      densities, negative for a C-terminal antibody and strongly positive for the 6E10
      antibody, clearly showing abnormal intracellular accumulation of sAPPalpha in
      response to Abeta. Our data support a dynamic model for intracellular retention
      of sAPPalpha as an early response to Abeta exposure. Particularly noteworthy was
      the observation that removal of Abeta reversed the isAPP accumulation.
      Mechanistically, these findings disclose an attractive physiological response,
      revealing the capacity of cells to deal with adverse effects induced by Abeta.

PMID- 19105197
TI  - Calpain-mediated degradation of G-substrate plays a critical role in retinal
      excitotoxicity for amacrine cells.
AB  - The role of neuronal N-methyl-D-aspartate (NMDA) receptor-mediated intracellular
      signaling has been elucidated in both physiological and pathological conditions.
      However, the details of relative vulnerability for excitotoxicity remain unknown.
      Retinal excitotoxicity is involved in various diseases leading to irreversible
      blindness. Here, we used the visual system and explored the mechanistic details
      of the NMDA-elicited intracellular events, especially in the amacrine cells,
      which are the most vulnerable type of neuron in the retina. G-substrate, a
      specific substrate of cyclic guanosine 3',5'-monophosphate (cGMP)-dependent
      protein kinase, is colocalized with amacrine cells and acts as an endogenous
      inhibitor of protein phosphatase. To elucidate how G-substrate was involved in
      NMDA-induced amacrine cell death, the immunohistochemical analysis with G
      substrate antibody was performed following NMDA injury. In vivo, NMDA immediately
      decreased G-substrate immunoreactivity, and the suppression of calpain activation
      using ALLN or calpain III, an inhibitor of calpain, blocked this decrease. In
      vitro, degraded fragments of G-substrate were detected within 10 min after
      coincubation of G-substrate and calpain. Moreover, G-substrate knockout (G
      substrate(-/-)) mice were more susceptible to NMDA injury than wild-type mice.
      ALLN did not have a neuroprotective effect in G-substrate(-/-) mice. These data
      strongly suggest that calpain-mediated loss of G-substrate represents an
      important mechanism contributing to NMDA-induced amacrine cell death.

PMID- 19105199
TI  - Association of reduced folate carrier gene polymorphism and maternal folic acid
      use with neural tube defects.
AB  - This study was designed to investigate whether the risk for neural tube defects
      (NTDs) was associated with reduced folate carrier gene (RFC1 A80G) polymorphism
      and/or with the interaction between the RFC1 gene and maternal periconceptional
      use of folic acid. One hundred four nuclear families with NTDs and 100 non
      malformed control families were sampled to investigate the potential interaction
      between maternal or the offspring's RFC1 (A80G) genotypes and the maternal
      periconceptional use of folic acid through a population-based case-control study.
      RFC1 (A80G) genotypes were detected using PCR-restricted fragment length
      polymorphism (PCR-RFLP). Mother who had the GG genotype and did not take folic
      acid had an elevated risk for NTDs (OR = 5.43, 95% CI = 1.68-18.28) as compared
      to the mother who had AA or GA genotype and took maternal periconceptional folic
      acid. The interactive coefficient was 1.12 between maternal GG genotype and the
      periconceptional folic acid non-use. The risk for having an infant with NTDs was
      8.80 (95% CI = 2.83-28.69) for offspring with the GG genotype, as compared to the
      offspring with AA or GA genotype among the mothers who did not take folic acid
      supplements. The interactive coefficient was 1.45 for offspring with the GG
      genotype and without maternal periconceptional supplementation of folic acid. Our
      findings suggest that there is a potential gene-environment interaction on the
      risk of NTDs between maternal or offspring RFC1 GG genotype and maternal
      periconceptional intake of folic acid. The RFC1 is likely to be an important
      candidate gene in folate transportation and RFC1 GG genotype (A80G) may be
      associated with an increased risk for NTDs in this Chinese population.

PMID- 19105198
TI  - Developmentally regulated and evolutionarily conserved expression of SLITRK1 in
      brain circuits implicated in Tourette syndrome.
AB  - Tourette syndrome (TS) is an inherited developmental neuropsychiatric disorder
      characterized by vocal and motor tics. Multiple lines of neurophysiological
      evidence implicate dysfunction in the corticostriatal-thalamocortical circuits in
      the etiology of TS. We recently identified rare sequence variants in the Slit and
      Trk-like family member 1 (SLITRK1) gene associated with TS. SLITRK1, a single
      pass transmembrane protein, displays similarities to the SLIT family of secreted
      ligands, which have roles in axonal repulsion and dendritic patterning, but its
      function and developmental expression remain largely unknown. Here we provide
      evidence that SLITRK1 has a developmentally regulated expression pattern in
      projection neurons of the corticostriatal-thalamocortical circuits. SLITRK1 is
      further enriched in the somatodendritic compartment and cytoplasmic vesicles of
      cortical pyramidal neurons in mouse, monkey, and human brain, observations
      suggestive of an evolutionarily conserved function in mammals. SLITRK1 is
      transiently expressed in the striosomal/patch compartment of the mammalian
      striatum and moreover is associated with the direct output pathway; adult
      striatal expression is confined to cholinergic interneurons. These analyses
      demonstrate that the expression of SLITRK1 is dynamic and specifically associated
      with the circuits most commonly implicated in TS and related disorders,
      suggesting that SLITRK1 contributes to the development of corticostriatal
      thalamocortical circuits.

PMID- 19105200
TI  - Association of major depression with rare functional variants in norepinephrine
      transporter and serotonin1A receptor genes.
AB  - Dysregulations of central noradrenergic and serotonergic neurotransmission have
      been suggested to contribute to the pathogenesis of neuropsychiatric disorders
      such as depression. The norepinephrine transporter (NET; SLC6A2) and the
      serotonin (5-HT)(1A) receptor (5-HT(1A) receptor; HTR1A) play an important role
      in central nervous monoaminergic homeostasis. As shown previously, variations in
      the human NET and 5-HT(1A) receptor genes can alter noradrenergic and
      serotonergic signaling in the brain: a single nucleotide polymorphism (SNP) in
      the coding region of the NET gene resulting in a F528C substitution increased
      plasma membrane expression of this NET variant, and a SNP in the human 5-HT(1A)
      receptor gene leading to the R219L receptor variant almost abolished cellular
      signal transduction subsequent to receptor activation. The present study aimed at
      investigating whether these NET and 5-HT(1A) receptor variants are associated
      with major depression (MD). The sample comprised 426 patients suffering from
      unipolar MD as well as 643 healthy control subjects for the variants of the 5
      HT(1A) receptor and the NET. Both SNPs were shown to be associated with MD. In
      conclusion, our results favor the hypothesis that monoaminergic neurotransmission
      in general and the F528C NET and R219L 5-HT(1A) receptor variants in particular
      are involved in the pathogenesis of depression.

PMID- 19105201
TI  - Transcription factor 7-like 2 polymorphism modulates glucose and lipid
      homeostasis, adipokine profile, and hepatocyte apoptosis in NASH.
AB  - Genetic factors underlying the association of NAFLD with diabetes and
      atherosclerosis are unknown. Recent human studies suggest transcription factor 7
      like 2 (TCF7L2) polymorphism predisposes to diabetes through modulation of beta
      cell function and modulates lipid levels in familial dyslipidemia. Emerging
      experimental evidence connects TCF7L2 to adipocyte metabolism and lipid
      homeostasis, as well. We tested if TCF7L2 polymorphism is a risk factor for
      nonalcoholic fatty liver disease (NAFLD) and if it modulates liver injury,
      glucose homeostasis, lipoprotein, and adipokine profiles in NASH. TCF7L2 genotype
      and dietary habits of 78 nondiabetic normolipidemic NAFLD subjects and 156 age-,
      body mass index-, sex-matched healthy controls were assessed. In 39 biopsy-proven
      nonalcoholic steatohepatitis (NASH) and matched controls TCF7L2 polymorphism was
      correlated to liver histology and oral glucose tolerance test-derived parameters
      of glucose homeostasis. Patients with NASH and controls consumed a high-fat meal
      and TCF7L2 genotype was correlated to postprandial circulating lipoproteins,
      adipokines, and cytokeratin-18 fragments. The TCF7L2 CT/TT genotype was more
      frequent in NAFLD and predicted the presence and severity of liver disease, of
      beta-cell dysfunction, of reduced incretin effect and hepatic insulin resistance
      in NASH; it also modulated postprandial hepatocyte apoptosis, lipoproteins, and
      adipokine profiles in both groups. CONCLUSION: TCF7L2 polymorphism predisposes to
      NAFLD and significantly impacts liver injury, glucose homeostasis, and
      postprandial lipoprotein and adipokine responses to fat ingestion. This
      polymorphism also modulates a fat-induced increase in circulating markers of
      hepatocyte apoptosis in NASH. Targeting postprandial lipemia, at least in at-risk
      TCF7L2 genotypes, may improve liver disease and glucose dysmetabolism in these
      patients.

PMID- 19105202
TI  - Impact of the dopamine receptor gene family on temperament traits in a population
      based birth cohort.
AB  - Although the genetic determinants of personality have been intensively
      investigated especially since Cloninger proposed his psychobiological model of
      temperament and character, findings to date remain inconclusive and very few
      studies have addressed the topic in large population cohorts. In the current
      study we investigated one gene family in its entirety by addressing the role of
      all known dopamine receptor genes, DRD1-DRD5, on Cloninger's temperament traits
      in a Finnish population-based birth cohort. The study sample (n = 1,434) was
      ascertained from the Northern Finland Birth Cohort 1966 with over 5,000 study
      individuals tested at the age of 31 years. We utilized the genetic homogeneity
      and genealogical structure of this population to uncover putative effects of
      these genes on temperament traits at the population level. Our strategy utilizing
      a large birth cohort and its well established genealogical structure represents
      an optimal design for studying normally distributed traits. We also wished to
      provide a comprehensive view to one biologically relevant gene family instead of
      testing single candidate genes. We report evidence of association of several SNPs
      at the 5' end of dopamine receptor D2 (DRD2) with Novelty seeking (low) and Harm
      avoidance (high), and at the 3' end of DRD2 with Persistence. The strongest
      evidence of association emerged from females. Our study supports the involvement
      of the dopamine pathway in temperament traits, in particular underlining the role
      of DRD2 in Novelty seeking, Harm avoidance and Persistence.

PMID- 19105203
TI  - An association analysis of Alzheimer disease candidate genes detects an ancestral
      risk haplotype clade in ACE and putative multilocus association between ACE, A2M,
      and LRRTM3.
AB  - Alzheimer's disease (AD) is the most common form of progressive dementia in the
      elderly. It is a neurodegenerative disorder characterized by the neuropathologic
      findings of neurofibrillary tangles and amyloid plaques that accumulate in
      vulnerable brain regions. AD etiology has been studied by many groups, but since
      the discovery of the APOE epsilon4 allele, no further genes have been mapped
      conclusively to late-onset AD (LOAD). In this study, we examined genetic
      association with LOAD susceptibility in 738 Caucasian families (4,704
      individuals) and an independent case-control dataset with 296 cases and 566
      controls exploring 11 candidate genes (47 SNPs common to both samples). In
      addition to tests for main effects and haplotypes, the MDR-PDT was used to search
      for gene-gene interactions in the family data. We observed significant haplotype
      effects in ACE in family and case-control samples using standard and cladistic
      haplotype models. ACE was also part of significant 2 and 3-locus MDR-PDT joint
      effects models with Alpha-2-Macroglobulin (A2M), which mediates the clearance of
      Abeta, and Leucine-Rich Repeat Transmembrane-3 (LRRTM3), a nested gene in Alpha-3
      Catenin (CTNNA3) which binds Presenilin-1. This result did not replicate in the
      case-control sample, and may not be a true positive. These genes are related to
      Abeta clearance; thus this constellation of effects might constitute an axis of
      susceptibility for LOAD. The consistent ACE haplotype result between independent
      family-based and unrelated case-control datasets is strong evidence in favor of
      ACE as a susceptibility locus for AD, and replicates results from several other
      studies in a large sample.

PMID- 19105205
TI  - Ethnic differences in hepatic steatosis: an insulin resistance paradox?
AB  - Nonalcoholic fatty liver disease is a burgeoning problem. We have previously
      shown that Hispanics were at greater risk for nonalcoholic fatty liver disease
      than were African-Americans despite a similar prevalence of risk factors between
      these groups. We have performed the largest, population-based study to date (n =
      2170) utilizing proton magnetic resonance (MR) spectroscopy, dual-energy x-ray
      absorptiometry, and multislice abdominal MR imaging to determine the contribution
      of body fat distribution to the differing prevalence of hepatic steatosis in the
      three major U.S. ethnic groups (African-American, Hispanic, Caucasian). Despite
      controlling for age and total adiposity, African-Americans had less
      intraperitoneal (IP) fat and more lower extremity fat than their Hispanic and
      Caucasian counterparts. The differences in hepatic triglyceride content (HTGC)
      between these groups remained after controlling for total, abdominal
      subcutaneous, and lower extremity adiposity; however, controlling for IP fat
      nearly abolished the differences in HTGC, indicating a close association between
      IP and liver fat regardless of ethnicity. Despite the lower levels of IP and
      liver fat in African-Americans, their prevalence of insulin resistance was
      similar to Hispanics, who had the highest levels of IP and liver fat.
      Furthermore, insulin levels and homeostasis model assessment values were highest
      and serum triglyceride levels were lowest among African-Americans after
      controlling for IP fat. CONCLUSION: IP fat is linked to HTGC, irrespective of
      ethnicity. The differing prevalence of hepatic steatosis between these groups was
      associated with similar differences in visceral adiposity. The metabolic response
      to obesity and insulin resistance differs in African-Americans when compared to
      either Hispanics or Caucasians: African-Americans appear to be more resistant to
      both the accretion of triglyceride in the abdominal visceral compartment (adipose
      tissue and liver) and hypertriglyceridemia associated with insulin resistance.

PMID- 19105204
TI  - The FMR1 gene and fragile X-associated tremor/ataxia syndrome.
AB  - The CGG-repeat present in the 5'UTR of the FMR1 gene is unstable upon
      transmission to the next generation. The repeat is up to 55 CGGs long in the
      normal population. In fragile X patients, a repeat length exceeding 200 CGGs
      (full mutation: FM) generally leads to methylation of the repeat and the promoter
      region, which is accompanied by silencing of the FMR1 gene. The gene product FMRP
      is involved in regulation of transport and translation of certain mRNA in the
      dendrite, thereby affecting synaptic plasticity. This is central to learning and
      memory processes. The absence of FMRP seen in FM is the cause of the mental
      retardation seen in fragile X patients. The premutation (PM) is defined as 55-200
      CGGs. Female PM carriers are at risk of developing primary ovarian insufficiency.
      Recently it was discovered that elderly PM carriers might develop a progressive
      neurodegenerative disorder called fragile X-associated tremor/ataxia syndrome.
      Although arising from the mutations in the same gene, distinct mechanisms lead to
      fragile X syndrome (absence of FMRP) and FXTAS (toxic RNA gain of function). The
      pathogenic mechanisms thought to underlie these disorders are discussed, with a
      specific emphasis on FXTAS. This review gives insight on the implications of all
      possible repeat length categories seen in fragile X families.

PMID- 19105207
TI  - Autochthonous liver tumors induce systemic T cell tolerance associated with T
      cell receptor down-modulation.
AB  - The reason the adaptive immune system fails in advanced liver tumors is largely
      unclear. To address this question, we have developed a novel murine model that
      combines c-myc-induced autochthonous tumorigenesis with expression of a cognate
      antigen, ovalbumin (OVA). When c-myc/OVA transgenic mice were crossed with liver
      specific inducer mice, multifocal hepatocellular carcinomas co-expressing OVA
      developed in a tetracycline-dependent manner with a short latency and 100%
      penetrance. Transferred OVA-specific T cells, although infiltrating the tumor at
      high numbers, were hyporesponsive, as evidenced by a lack of in vivo cytotoxicity
      and interferon gamma production. This allowed the tumor to progress even in the
      presence of large numbers of antigen-specific T cells and even after vaccination
      (OVA+CpG-DNA). Interestingly, T cell receptor down-modulation was observed, which
      may explain antigen-specific hyporesponsiveness. This model is helpful in
      understanding liver cancer-specific mechanisms of T cell tolerance and dissection
      of antigen-specific and nonspecific mechanisms of immunotherapies in the
      preclinical phase.

PMID- 19105206
TI  - Foxl1 is a marker of bipotential hepatic progenitor cells in mice.
AB  - The liver contains a population of small bipotential facultative progenitor cells
      that reconstitute liver function when mature hepatocytes or cholangiocytes are
      unable to proliferate. Mesenchymal markers, including members of the forkhead
      transcription factor gene family, have been detected in hepatic progenitor cells.
      The winged helix transcription factor Foxl1 localizes to mesenchymal cells in the
      intestine; however, its expression in the liver has not been reported. We found
      that Foxl1 is expressed in rare cells in the normal liver but is dramatically
      induced in the livers of mice that have undergone bile duct ligation or were fed
      a 3,5-diethoxycarbonyl-1,4-dihydrocollidine (DDC)-containing or choline
      deficient, ethionine-supplemented diet. In addition, we employed genetic lineage
      tracing using a Foxl1-Cre transgenic mouse crossed with the Rosa26R lacZ reporter
      line to demonstrate that Foxl1-Cre-expressing cells are present within the
      periportal region shortly after injury. These cells give rise to both hepatocytes
      [marked by hepatocyte nuclear factor 4 alpha (HNF-4alpha) expression] and
      cholangiocytes (marked by CK19 expression), indicating that these cells are
      derived from Foxl1-Cre-expressing cells. Foxl1-Cre-expressing cells are distinct
      from hepatic stellate cells, portal fibroblasts, and myofibroblasts, although
      they are located in close proximity to portal fibroblasts. These results
      demonstrate that the early Foxl1-Cre lineage cell gives rise to both
      cholangiocytes and hepatocytes after liver injury and suggest the potential for
      progenitor-portal fibroblast cell interactions. CONCLUSION: We propose that Foxl1
      is a bona fide marker of the facultative progenitor cell in the mouse liver.

PMID- 19105208
TI  - Liver X receptor mediates hepatitis B virus X protein-induced lipogenesis in
      hepatitis B virus-associated hepatocellular carcinoma.
AB  - Although hepatitis B virus X protein (HBx) has been implicated in abnormal lipid
      metabolism in hepatitis B virus (HBV)-associated hepatic steatosis, its
      underlying molecular mechanism remains unclear. Liver X receptor (LXR) plays an
      important role in regulating the expression of genes involved in hepatic
      lipogenesis. Here we demonstrate that LXRalpha and LXRbeta mediate HBV-associated
      hepatic steatosis. We have found that HBx induces the expression of LXR and its
      lipogenic target genes, such as sterol regulatory element binding protein-1c
      (SREBP-1c), fatty acid synthase (FAS), and peroxisome proliferator-activated
      receptor, and this is accompanied by the accumulation of lipid droplets. RNA
      interference with LXR expression decreases the amount of lipid droplets as well
      as the expression of the lipogenic genes, and this indicates that HBx-induced
      lipogenesis is LXR-dependent. LXRalpha and HBx colocalize in the nucleus and are
      physically associated. HBx induces the transactivation function of LXRalpha by
      recruiting CREB binding protein to the promoter of the target gene. Furthermore,
      we have observed that expression of LXR is increased in the livers of HBx
      transgenic mice. Finally, there is a significant increase in the expression of
      LXRbeta (P = 0.036), SREBP-1c (P = 0.008), FAS, and stearoyl-coenyzme A
      desaturase-1 (P = 0.001) in hepatocellular carcinoma (HCC) in comparison with
      adjacent nontumorous nodules in human HBV-associated HCC specimens. CONCLUSION:
      Our results suggest a novel association between HBx and LXR that may represent an
      important mechanism explaining HBx-induced hepatic lipogenesis during HBV
      associated hepatic carcinogenesis.

PMID- 19105209
TI  - Allelic imbalances and homozygous deletion on 8p23.2 for stepwise progression of
      hepatocarcinogenesis.
AB  - Early hepatocellular carcinoma (eHCC) originates from the hepatocytes of chronic
      liver disease and develops into classical hepatocellular carcinoma (HCC). To
      identify sequential genetic changes in multistep hepatocarcinogenesis, we
      analyzed molecular karyotypes using oligonucleotide genotyping 50K arrays. First,
      1q21.3-44 gain and loss of heterozygosity (LOH) on 1p36.21-36.32 and 17p13.1-13.3
      were frequently observed in eHCC, but not in chronic liver diseases, suggesting
      that such chromosomal aberrations are early, possibly causative events in liver
      cancer. Next, we detected 25 chromosomal loci associated with liver cancer
      progression in five HCCs with nodule-in-nodule appearance, in which the inner
      nodule develops within eHCC lesion. Using these chromosomal regions as
      independent variables, decision tree analysis was applied on 14 early and 25
      overt HCCs, and extracted combination of chromosomal gains on 5q11.1-35.3 and
      8q11.1-24.3 and LOH on 4q11-34.3 and 8p11.21-23.3 as distinctive attributes,
      which can classify early and overt HCCs recursively. In these four altered
      regions identified as late events of hepatocarcinogenesis, two tumors in 32 overt
      HCCs analyzed in the present study and one in a set of independent samples of 36
      overt HCCs in our previous study harbored a homozygous deletion near the CSMD1
      locus on 8p23.2. CSMD1 messenger RNA expression was decreased in HCC without
      8p23.2 deletion, possibly due to hypermethylation of the CpG islands in its
      promoter region. CONCLUSION: 1q gain and 1p and 17p LOH are early molecular
      events, whereas gains in 5q and 8q and LOH on 4q and 8p only occur in advanced
      HCC, and inactivation of the putative suppressor gene, CSMD1, may be the key
      event in progression of liver cancer.

PMID- 19105210
TI  - The Marburg I variant (G534E) of the factor VII-activating protease determines
      liver fibrosis in hepatitis C infection by reduced proteolysis of platelet
      derived growth factor BB.
AB  - Genetic risk factors play an important role for the progression of liver fibrosis
      in chronic hepatitis C virus (HCV) infection, but functional data on specific
      alleles and their related proteins are limited. Platelet-derived growth factor BB
      (PDGF-BB) is one of the strongest mitogens for hepatic stellate cells and is
      considered as a critical soluble mediator of liver fibrosis in vitro and in vivo.
      The biological activity of PDGF-BB is dependent on its degradation by the factor
      VII-activating protease (FSAP). Here, we demonstrate that a coding polymorphism
      (G534E) in the gene for FSAP is significantly associated with severe HCV-induced
      liver fibrosis (odds ratio, 2.59; P = 0.017), which is independent of age,
      gender, and presence of diabetes in multivariate analysis. These genetic findings
      were replicated in a cohort of patients with liver transplantation due to HCV
      induced cirrhosis (OR, 2.56; P = 0.011). Functional dissection of the association
      demonstrates that the single amino acid change encoded by G534E in the FSAP
      protein does not influence PDGFbeta receptor or alpha-smooth muscle actin
      expression but completely abrogates FSAP-mediated inhibition of PDGF-BB-induced
      proliferation of primary stellate cells in vitro. CONCLUSION: The G534E variant
      of FSAP is a risk locus for HCV-induced liver fibrosis and cirrhosis by
      determining PDGF-BB-mediated hepatic stellate cell proliferation through a single
      amino acid substitution in FSAP. FSAP G534E might be useful for risk
      stratification in patients with HCV infection.

PMID- 19105211
TI  - Occult hepatitis C: how convincing are the current data?

PMID- 19105212
TI  - A randomized trial of the anti-depressant effects of low- and high-frequency
      transcranial magnetic stimulation in treatment-resistant depression.
AB  - BACKGROUND: The majority of studies investigating the effectiveness of repetitive
      transcranial magnetic stimulation (rTMS) as a treatment for major depression have
      focused on high-frequency rTMS to the left prefrontal cortex (HFL-rTMS). In
      addition, low-frequency right prefrontal rTMS (LFR-rTMS) has also been shown to
      have antidepressant properties. To date only a small number of studies have
      directly compared the efficacy of these two approaches. METHODS: The aim of this
      study, therefore, was to investigate further whether LFR-rTMS is as effective as
      HFL-rTMS in the treatment of major depression. Twenty-seven patients were
      randomized to one of two treatment arms (HFL-rTMS or LFR-rTMS) for 3 weeks with a
      possible 1-week extension. Non-responders were offered the opportunity of
      crossing over to the other treatment type. Stimulation parameters for HFL-rTMS
      were 30 stimulation trains of 5 s duration at 100% of the resting motor threshold
      (RMT); for LFR-rTMS, stimulation was applied in four trains of 180 s duration (30
      s inter-train interval) at 110% of the RMT. Stimulation was provided 5-week days
      per week. RESULTS: There were significant improvements seen from baseline to end
      point irrespective of group and on all clinical outcome measures. In addition,
      there was no deterioration in any of the measures used to assess cognitive
      change, and significant improvements were seen on measures of immediate verbal
      memory and verbal fluency. CONCLUSIONS: HFL-rTMS and LFR-rTMS appear to be
      equally efficacious in treating major depression. This study adds to the growing
      literature supporting LFR-rTMS as an additional viable method of rTMS delivery in
      the treatment of depression.

PMID- 19105213
TI  - Startle response in generalized anxiety disorder.
AB  - BACKGROUND: The main purpose of the present study was to examine the startle
      reflex in individuals diagnosed with Generalized Anxiety Disorder (GAD) and
      control participants in terms of three questions. First, is the basic startle
      reflex modulated by autonomic nervous system (ANS) activation and/or attentional
      focus? Second, are induced and self-reported emotional states related to the
      magnitude of the startle response? And third, do individuals with GAD and their
      controls show differential startle responses? METHODS: Experimental tasks
      designed to elicit sympathetic and parasympathetic activation and requiring
      internal and external attention foci were administered to nine individuals with
      GAP and nine controls. RESULTS: Individuals with GAD showed a greater startle
      reflex than controls during involvement in tasks that either induced worry or
      relaxation but not during a baseline period. Startle responses differed in terms
      of intentional focus but not ANS activity. During baseline and emotional
      induction, self-reported negative emotionality was significantly correlated with
      magnitude of the startle response. CONCLUSIONS: These results suggest that
      negative emotionality at the time of the startle probe is an important
      determinant. Further, attentional focus plays a more important role in startle
      modulation than autonomic nervous system manipulation. These results are
      discussed in relation to negative emotion, focus of attention, and use of the
      startle response as a measure of change during psychotherapy.

PMID- 19105214
TI  - Immune manipulation of advanced breast cancer: an interpretative model of the
      relationship between immune system and tumor cell biology.
AB  - This review summarizes some recent clinical immunological approaches with
      cytokines and/or antibodies for therapy of advanced breast cancer. It considers
      the recent advances in genetics and molecular tumor biology related to impaired
      immunosurveillance involving cytokines and growth factors to explain clinical
      results. Evasion of the host immune attack might be induced by the following
      groups of mechanisms: (a) tumor dependent (genomic instability, HLA class I
      antigen abnormalities, upregulation of fetal type nonclassical HLA class I
      molecules, epitope immunodominance, apoptosis inhibition by defective death
      receptor signaling, apoptosis of activated T cells, tumor cannibalism and
      constitutive activation of signal transducer, and activator of transcription-3
      (Stat 3) and nuclear factor-kappaB (NF-kappaB) signaling); (b) host dependent
      (CD4+CD25+ regulatory T cells (T reg), CD4+ T cells anergy, Th2 antitumor
      immunity diversion and myeloid suppressor cells); (c) tumor and host dependent
      (lack of co-stimulation molecules, immunosuppressive cytokines (vascular
      endothelial growth factor (VEGF), interleukin (IL)-10, prostaglandin (PG)E2,
      transforming growth factor (TGF)-beta)). Cytokines and growth factors are
      involved in virtually all three types of mechanisms. These mechanisms are
      integrated with the current knowledge of tumor growth and inhibited apoptosis
      primarily mediated by cytokines and growth factors to propose an interpretation
      of the relationships among tumor cells, tumor stroma, and tumor-infiltrating
      lymphocytes. Tumor growth, defective immunorecognition and immunosuppression are
      the three principal effects considered responsible for immune evasion.

PMID- 19105215
TI  - The JIP3 scaffold protein UNC-16 regulates RAB-5 dependent membrane trafficking
      at C. elegans synapses.
AB  - How endosomes contribute to the maintenance of vesicular structures at
      presynaptic terminals remains controversial and poorly understood. Here, we have
      investigated synaptic endosomal compartments in the presynaptic terminals of C.
      elegans GABAergic motor neurons. Using RAB reporters, we find that several
      subsynaptic compartments reside in, or near, presynaptic regions. Loss of
      function in the C. elegans JIP3 protein, UNC-16, causes a RAB-5-containing
      compartment to accumulate abnormally at presynaptic terminals. Ultrastructural
      analysis shows that synapses in unc-16 mutants contain reduced number of synaptic
      vesicles, accompanied by an increase in the size and number of cisternae. FRAP
      analysis revealed a slow recovery of RAB-5 in unc-16 mutants, suggestive of an
      impairment of RAB-5 activity state and local vesicular trafficking.
      Overexpression of RAB-5:GDP partially suppresses, whereas overexpression of RAB
      5:GTP enhances, the synaptic defects of unc-16 mutants. Our data demonstrate a
      novel function of UNC-16 in the regulation of synaptic membrane trafficking and
      suggest that the synaptic RAB-5 compartment contributes to synaptic vesicle
      biogenesis or maintenance.

PMID- 19105216
TI  - De novo DNA methylation independent establishment of maternal imprint on X
      chromosome in mouse oocytes.
AB  - Mouse blastocyst stage embryo stained for histone H3 lysine-27 trimethylation
      (red) and DNA (blue). H3K27me3 marks the inactive X chromosome. The study by
      Chiba et al. in this issue suggests that de novo DNA methyltransferases are
      dispensable for setting the imprint on the maternally-derived X chromsome in
      growing oocytes. See Chiba et al. in this issue.

PMID- 19105217
TI  - Tamoxifen modulates apoptosis in multiple modes of action in CreER mice.
AB  - Tamoxifen-inducible Cre (CreER) has become a powerful tool for in vivo
      manipulation of the genome. Here, we investigated opposing effects of tamoxifen
      on apoptosis during embryogenesis using Olig2-CreER knock-in mice, namely,
      tamoxifen-induced apoptosis through CreER-mediated toxicity and cytoprotective
      activity of tamoxifen independent of CreER. First, we examined tamoxifen-induced
      apoptosis; in the homozygous mice, we observed region-specific apoptosis in the
      ventral neural tube, with no obvious increase in the heterozygotes. Next, we
      detected a cytoprotective effect on apoptosis in the homozygous dorsal root
      ganglia (DRG). This apoptosis is a secondary phenotype of Olig2-null mice, as
      Olig2/CreER is not expressed in the DRG. The cytoprotective effect is DRG
      specific, because tamoxifen did not rescue apoptosis in the interdigital
      mesenchyme. These data indicate that tamoxifen has multiple effects on apoptosis
      during development and caution that careful examination is necessary when
      interpreting results obtained from tamoxifen-induced recombination: in Olig2
      CreER mice, heterozygotes are usable for lineage-tracing experiment without
      obvious toxicity, while homozygotes show efficient recombination, despite
      enhanced apoptosis.

PMID- 19105218
TI  - Duration effect of obsessive-compulsive disorder on cognitive function: a
      functional MRI study.
AB  - BACKGROUND: The inconsistency of previous reports examining cognitive function in
      obsessive-compulsive disorder (OCD) suggests its heterogeneity. In this study, we
      examined the effect of illness duration on cognitive function in OCD. METHODS: We
      examined the cognitive function of 32 OCD patients and 16 healthy volunteers by
      neuropsychological tests and functional magnetic resonance imaging while they
      performed the Stroop and N-back tasks to assess attention and nonverbal memory.
      The patients were divided into two groups by illness duration: a short-term group
      (n=17, 5.5+/-3.1 years) and a long-term group (n=15, 20.3+/-6.1 years).
      Statistical analysis was performed to determine the differences between these two
      groups and the normal control group (n=16). RESULTS: The long-term group showed
      attention deficit and nonverbal memory dysfunction on the neuropsychological
      tests. In contrast, on functional magnetic resonance imaging, the short-term
      group showed weaker activation of the right caudate during the Stroop task and
      stronger activation of the right dorso-lateral prefrontal cortex during the N
      back task than the long-term and normal control groups. CONCLUSIONS: The results
      suggested that abnormal brain activation occurs in the early phase of OCD and
      that the long-term persistence of OCD might involve a decline in cognitive
      function.

PMID- 19105219
TI  - Negative affectivity in smokers applying to smoking cessation clinics: a case
      control study.
AB  - OBJECTIVE: The objective of this study was to assess whether subjects applying to
      smoking cessation clinics display a higher level of affective symptoms than
      smokers recruited from the general population. METHODS: The study was conducted
      according to a cross-sectional, case-control design. Cases were smokers applying
      to public smoking cessation clinics for the first time and controls were smokers
      recruited from the general population. Socio-demographic data and clinical
      information were collected. Self- (Hospital Anxiety Depression Scale, Beck
      Depression Inventory, State-Trait Anxiety Inventory) and hetero-administered
      (Montgomery Asberg Depression Rating Scale, Hamilton Anxiety scale) rating scales
      were used to assess anxious and depressive symptoms. Nicotine dependence was
      measured via a self-administered questionnaire (Fagerstrom Tolerance
      Questionnaire). RESULTS: Sixty-eight cases were recruited, individually matched,
      and compared to controls. Overall, cases had significantly higher scores than
      controls when the rating scales assessing anxious and depressive symptoms were
      evaluated. CONCLUSIONS: Smokers applying to smoking cessation clinics for the
      first time have a higher level of negative affectivity than smokers from the
      general population. An evaluation of the level of negative affectivity could be
      introduced into clinical practice to have a complete assessment of the patient.
      We propose adding psychological or pharmacological support to complement the
      smoking cessation program.

PMID- 19105220
TI  - Does 5-HTTLPR genotype influence willingness to participate in panic challenges?

PMID- 19105221
TI  - Processing of facial affect under social threat in socially anxious adults: mood
      matters.
AB  - BACKGROUND: An important function of the human face is to communicate approval or
      disapproval toward others. Because socially anxious individuals are overly
      concerned about disapproval by others, it has been hypothesized that those
      individuals are faster at processing negative, specifically angry facial
      expressions than nonanxious individuals, especially under conditions of social
      threat. METHOD: To test this hypothesis, 25 socially anxious individuals and 24
      nonanxious controls were asked to classify facial expressions associated with
      anger, sadness, fear, disgust, happiness, and surprise. Half of the participants
      performed this task while being confronted with social threat. RESULTS: High
      socially anxious participants were faster than controls at classifying angry,
      sad, and fearful faces when confronted with social threat. No group difference
      was observed under the no-threat condition. CONCLUSIONS: The findings suggest
      that socially anxious individuals are more hypervigilant toward threat-related
      social cues, and that the processing of facial affect is dependent on the
      person's emotional state.

PMID- 19105222
TI  - Multinuclear NMR characterisation and dermal delivery of fluorinated drugs in
      soybean-microemulsion systems.
AB  - The present study evaluated the effect of different commercially available
      soybean lecithins in microemulsion systems in terms of microstructure
      transformation, physicochemical properties and transport of selected entrapped
      fluorinated drugs through skin. Physicochemical characterisations by particle
      size and polydispersity index (PDI) measurements were performed and a direct
      correlation with NMR self-diffusion coefficients of the individual components was
      found. An increase of lysophosphatidylcholine (LPC), phosphatidylethanolamine
      (PE) and lysophosphatidylethanolamine (LPE) in the phospholipid mixtures
      increased the mean particle sizes and PDI. Bicontinous microemulsion structures
      were proven by 1H and 31P NMR in the placebo microemulsions. Reasonable
      permeation of the lipophilic drugs of all microemulsions systems was confirmed in
      standard diffusion studies using porcine skin. This could be due to the
      incorporation of the drugs in the surfactant structure of the lecithin based
      bicontinous micro textures, as proven by 19F NMR self-diffusion studies.

PMID- 19105223
TI  - Gene targeted ablation of high molecular weight fibroblast growth factor-2.
AB  - Fibroblast growth factor-2 (FGF2) is produced as high molecular weight isoforms
      (HMW) and a low molecular weight isoform (LMW) by means of alternative usage of
      translation start sites in a single Fgf2 mRNA. Although the physiological
      function of FGF2 and FGF2 LMW has been investigated in myocardial
      capillarogenesis during normal cardiac growth, the role of FGF2 HMW has not been
      determined. Here, we report the generation of FGF2 HMW-deficient mice in which
      FGF2 HMW isoforms are ablated by the Tag-and-Exchange gene targeting technique.
      These mice are normal and fertile with normal fecundity, and have a normal life
      span. Histological, immunohistochemical, and morphometric analyses indicate
      normal myocardial architecture, blood vessel, and cardiac capillary density in
      young adult FGF2 HMW-deficient mice. These mice along with the FGF2- and FGF2 LMW
      deficient mice that we have generated previously will be very useful for
      elucidating the differential functions of FGF2 isoforms in pathophysiology of
      cardiovascular diseases.

PMID- 19105224
TI  - Multilayer tendon slices seeded with bone marrow stromal cells: a novel composite
      for tendon engineering.
AB  - The ideal scaffold for tendon engineering would possess the basic structure of
      the tendon, native extracellular matrix, and capability of cell seeding. The
      purpose of this study was to assess the tissue engineering potential of a novel
      composite consisting of a decellularized multilayer sliced tendon (MST) scaffold
      seeded with bone marrow stromal cells (BMSC). BMSC and infraspinatus tendons were
      harvested from 20 dogs. The tendons were sectioned in longitudinal slices with a
      thickness of 50 microm. The slices were decellularized, seeded with BMSC, and
      then bundled into one composite. The composite was incubated in culture media for
      14 days. The resulting BMSC-seeded MST was evaluated by qRT-PCR and histology.
      The BMSC viability was assessed by a fluorescent tracking marker. Histology
      showed that the seeded cells aligned between the collagen fibers of the tendon
      slices. Analysis by qRT-PCR showed higher tenomodulin and MMP13 expression and
      lower collagen type I expression in the composite than in the BMSC before
      seeding. BMSC labeled with fluorescent tracking marker were observed in the
      composite after culture. Mechanical testing showed no differences between
      scaffolds with or without BMSC. BMSC can survive in a MST scaffold. The increased
      tenomodulin expression suggests that BMSC might express a tendon phenotype in
      this environment. This new composite might be useful as a model of tendon tissue
      engineering.

PMID- 19105225
TI  - Preliminary in vitro evaluation of an adjunctive therapy for extremity wound
      infection reduction: rapidly resorbing local antibiotic delivery.
AB  - Despite the continuing advances in treatment of open fractures and
      musculoskeletal wounds, infection remains a serious complication. Current
      treatments to prevent infection utilize surgical debridement and irrigation, and
      high doses of systemic antimicrobial therapy. The aim of this work was to
      evaluate, in vitro, the potential of a fast-resorbing calcium sulfate pellet
      loaded with an antibiotic. The pellet could be used as an adjunctive therapy at
      the time of debridement and irrigation to reduce bacterial wound contamination.
      Small pellets containing a binder and calcium sulfate were engineered to resorb
      rapidly (within 24 h) and deliver high local doses of antibiotic (amikacin,
      gentamicin, or vancomycin) to the wound site while minimizing systemic effects.
      Results from dissolution, elution, and biological activity tests against P.
      aeruginosa and S. aureus were used to compare the performance of antibiotic
      loaded, rapidly resorbing calcium sulfate pellets to antibiotic-loaded crushed
      conventional calcium sulfate pellets. Antibiotic-loaded rapidly resorbing pellets
      dissolved in vitro in deionized water in 12-16 h and released therapeutic
      antibiotic levels in phosphate buffered saline that were above the minimal
      inhibitory concentration for P. aeruginosa and S. aureus, completely inhibiting
      the growth of these bacteria for the life of the pellet. Crushed conventional
      calcium sulfate pellets dissolved over 4-6 days, but the eluates only contained
      sufficient antibiotic to inhibit growth for the first 4 h. These data indicate
      that fast-resorbing pellets can release antibiotics rapidly and at therapeutic
      levels. Adjunctive therapy with fast-acting pellets is promising and warrants
      further in vivo studies.

PMID- 19105226
TI  - Soluble and particulate Co-Cr-Mo alloy implant metals activate the inflammasome
      danger signaling pathway in human macrophages: a novel mechanism for implant
      debris reactivity.
AB  - Immune reactivity to soluble and particulate implant debris remains the primary
      cause of aseptic inflammation and implant loosening. However, the intracellular
      mechanisms that trigger immune cells to sense and respond to exogenous
      nonbiological agents such as metal particles or metal ions released from
      orthopedic implants remain unknown. Recent studies in immunology have outlined
      the importance of the intracellular inflammasome complex of proteins in sensing
      danger/stress signals triggered by nonbiological agents in the cytosol of
      macrophages. We hypothesized that metal implant debris can activate the
      inflammasome pathway in macrophages that causes caspase-1-induced cleavage of
      intracellular pro-IL-1beta into its mature form, resulting in IL-1beta secretion
      and induction of a broader proinflammatory response. We tested this hypothesis by
      examining whether soluble cobalt, chromium, molybdenum, and nickel ions and Co-Cr
      Mo alloy particles induce inflammasome- mediated macrophage reactivity. Our
      results demonstrate that these agents stimulate IL-1beta secretion in human
      macrophages that is inflammasome mediated (i.e., NADPH-, caspase-1-, Nalp3-, and
      ASC-dependent). Thus, metal ion- and particle-induced activation of the
      inflammasome in human macrophages provides evidence of a novel pathway of implant
      debris-induced inflammation, where contact with implant debris is sensed and
      transduced by macrophages into a proinflammatory response.

PMID- 19105228
TI  - Bio-corrosion of stainless steel by osteoclasts--in vitro evidence.
AB  - Most metals in contact with biological systems undergo corrosion by an
      electrochemical process. This study investigated whether human osteoclasts (OC)
      are able to grow on stainless steel (SS) and directly corrode the metal alloy
      leading to the formation of corresponding metal ions, which may cause
      inflammatory reactions and activate the immune system. Scanning electron
      microscopy analysis demonstrated long-term viable OC cultures and evident
      resorption features on the surface of SS discs on which OC were cultured for 21
      days. The findings were confirmed by atomic emission spectrometry investigations
      showing significantly increased levels of chromium, nickel, and manganese in the
      supernatant of OC cultures. Furthermore, significant levels of pro-inflammatory
      cytokines IL-1beta, IL-6, and TNF-alpha, which are considered to be major
      mediators of osteolysis, were revealed in the same cultures by cytometric bead
      array analysis. Within the present study, it was shown that human osteoclast
      precursors are able to grow and differentiate towards mature OC on SS. The mature
      cells are able to directly corrode the metal surface and release corresponding
      metal ions, which induce the secretion of pro-inflammatory cytokines that are
      known to enhance osteoclast differentiation, activation, and survival. Enhanced
      corrosion and the subsequently released metal ions may therefore result in
      enhanced osteolytic lesions in the peri-prosthetic bone, contributing to the
      aseptic loosening of the implant.

PMID- 19105227
TI  - Ischemic limb preconditioning downregulates systemic inflammatory activation.
AB  - We examined local and systemic antiinflammatory consequences of ischemic
      preconditioning (IPC) in a rat model of limb ischemia-reperfusion (I-R) by
      characterizing the leukocyte-endothelial interactions in the periosteum and the
      expression of adhesion molecules playing a role in leukocyte-mediated
      inflammatory processes. IPC induction (2 cycles of 10 min of complete limb
      ischemia and 10 min of reperfusion) was followed by 60 min of ischemia/180 min of
      reperfusion or sham-operation. Data were compared with those on animals subjected
      to I-R and sham-operation. Neutrophil leukocyte-endothelial cell interactions
      (intravital videomicroscopy), intravascular neutrophil activation (CD11b
      expression changes by flow cytometry), and soluble and tissue intercellular
      adhesion molecule-1 (ICAM-1; ELISA and immunohistochemistry, respectively)
      expressions were assessed. I-R induced enhanced leukocyte rolling and adherence
      in the periosteal postcapillary venules after 120 and 180 min of reperfusion.
      This was associated with a significantly enhanced CD11b expression (by
      approximately 80% and 72%, respectively) and moderately increased soluble and
      periosteal ICAM-1 expressions. IPC prevented the I-R-induced increases in
      leukocyte adherence and CD11b expression without influencing the soluble and
      tissue ICAM-1 levels. The results show that limb IPC exerts not only local, but
      distant antiinflammatory effects through significant modulation of neutrophil
      recruitment.

PMID- 19105229
TI  - Ketoprofen in topical formulation decreases the matrix metalloproteinase-2
      expression and pulmonary metastatic incidence in nude mice with osteosarcoma.
AB  - The aim of this study was to investigate whether ketoprofen (KP) in topical
      formulation affected the tumor growth and pulmonary metastasis of LM8 cells,
      which were inoculated subcutaneously into the back space of male nude mice. At 7
      days after inoculation, the tumor was treated topically for 3 weeks with either a
      KP-containing patch (KP group) or a placebo-containing patch (placebo group). The
      pulmonary metastatic incidence was 100% in the placebo group and 60% in the KP
      group. The tumor mass of the KP group without pulmonary metastasis, termed the
      KP/metastasis(-) group, was smaller than that of the placebo group.
      Immunohistochemical staining for proliferating cell nuclear antigen (PCNA),
      terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL),
      matrix metalloproteinase-2 (MMP-2), and vascular endothelial growth factor (VEGF)
      was performed. The tumors of the KP/metastasis(-) group contained fewer PCNA
      positive cells and many more TUNEL-positive cells in comparison to the placebo
      group. In the placebo group, MMP-2 and VEGF were extensively expressed within the
      tumor, whereas in the KP/metastasis(-) group the expression of these two proteins
      was very low. In conclusion, the topical treatment of osteosarcoma with KP
      decreased the expression of MMP-2 and VEGF, thus resulting in the suppression of
      tumor growth and pulmonary metastasis.

PMID- 19105230
TI  - Comparison of articular and auricular cartilage as a cell source for the
      autologous chondrocyte implantation.
AB  - Articular (medial femoral condyle) and auricular cartilage (anithelix) was
      compared as a cell source for the autologous joint repair. Cells isolated from
      five human cadaveric donors were cultured parallel in the monolayer cultures and
      in the 3D alginate hydrogel constructs for 1 week. Cell morphology was controlled
      by the fluorescent microscopy and gene expressions of type I collagen (COL1),
      type II collagen (COL2), aggrecan (AGR), versican (VER), and elastin (ELS) were
      analyzed by the real-time polymerase chain reaction. COL1 and ELS, predominant in
      the phenotype of auricular biopsy, were statistically lower in the articular
      biopsies. Even though COL2 and AGR decreased in monolayers of both cell sources,
      the dedifferentiation process affected auricular cells intensely. Cells embedded
      in the alginate hydrogel directly after the isolation did not exhibit the
      dedifferentiated phenotype. Additionally, COL1, COL2, AGR, and VER were
      comparable between the two sources. ELS however, remained higher in the auricular
      cells regardless of the culture type. The study indicates that auricular
      chondrocytes cultured in a 3D environment immediately after the isolation have a
      neo-cartilage potential for the articular surface reconstruction.

PMID- 19105231
TI  - Absence of the JAK2 exon 12 mutations in patients with splanchnic venous
      thrombosis and without overt myeloproliferative neoplasms.

PMID- 19105232
TI  - Cut-off value of red-blood-cell-bound IgG for the diagnosis of Coombs-negative
      autoimmune hemolytic anemia.
AB  - Direct antiglobulin test (DAT)-negative autoimmune hemolytic anemia (Coombs
      negative AIHA) is characterized by laboratory evidence of in vivo hemolysis,
      together with a negative DAT performed by conventional tube technique (CTT) in
      clinically suspected AIHA patients. The immunoradiometric assay (IRMA) for red
      blood-cell-bound immunoglobulin G (RBC-IgG) can be used to diagnose patients in
      whom CTT does not detect low levels of red cell autoantibodies. We investigated
      the diagnostic cutoff value of the IRMA for RBC-IgG in Coombs-negative AIHA and
      calculated its sensitivity and specificity. Of the 140 patients with negative DAT
      by CTT referred to our laboratory with undiagnosed hemolytic anemia, AIHA was
      clinically diagnosed in 64 patients (Coombs-negative AIHA). The numbers of Coombs
      negative AIHA and non-AIHA patients changed with age and gender. The cutoff
      values were determined from receiver operating characteristic (ROC) curve
      according to age and gender. The IRMA for RBC-IgG proved to be sensitive (71.4%)
      and specific (87.8%) when using these cutoffs. Using these cutoffs for 41
      patients with negative DAT referred to our laboratory in 2006, all the
      pseudonegative cases were treated with steroids before the test. The 31 untreated
      cases could be grouped using one cutoff value of 78.5 and showed 100% sensitivity
      and 94% specificity, independent of gender and age. Results indicate that RBC-IgG
      could become a standard approach for the diagnosis of Coombs-negative AIHA, when
      measured before treatment.

PMID- 19105233
TI  - Platelet turnover, coagulation factors, and soluble markers of platelet and
      endothelial activation in essential thrombocythemia: relationship with thrombosis
      occurrence and JAK2 V617F allele burden.
AB  - Patients with essential thrombocythemia (ET) have an increased frequency of
      thrombosis, but the relationship of both thrombosis and JAK2 V617F allele burden
      with platelet turnover, acquired activated protein C resistance (aAPCR), and
      levels of coagulation factors and soluble markers of platelet, and endothelial
      activation is not well known. In 53 ET patients (26 with a history of
      thrombosis), reticulated platelets (RP) percentage, aAPCR, platelet tissue factor
      (TF) expression, and plasma levels of TF, coagulation factors, soluble P-selectin
      (sP-selectin), soluble CD40 ligand (sCD40L), von Willebrand factor antigen
      (VWF:Ag), soluble thrombomodulin (sTM), D-dimer and prothrombin fragment 1 + 2
      were compared with those in matched healthy individuals and correlated with
      thrombosis occurrence and JAK2 mutational load. ET patients with thrombosis had
      significantly higher values for RP percentage, aAPCR, and levels of factors V and
      VIII, VWF:Ag, sP-selectin, and sCD40L than patients without thrombosis and
      controls. At multivariate study, RP percentage, factor V levels, and aAPCR were
      independently associated with an increased risk of thrombosis. Patients with JAK2
      mutation had significantly lower levels of free protein S (PS) and higher levels
      of TF, sP-selectin, sCD40L, VWF:Ag, and sTM than those with wild-type allele. A
      mutant allele dosage effect (>or= 12%) was observed for TF, sP-selectin, sCD40L,
      VWF:Ag, and PS levels. These results support a role for platelet turnover, factor
      V, and aAPCR in the thrombosis of ET as well as the association between JAK2
      V617F allele burden and either decreased free PS or increased TF and soluble
      markers of platelet and endothelial activation.

PMID- 19105234
TI  - Successful cell-mediated cytokine-activated immunotherapy for relapsed acute
      myeloid leukemia after hematopoietic stem cell transplantation.
AB  - Acute myeloid leukemia (AML) is an extremely aggressive disease with a high
      relapse rate even after allogeneic hematopoietic stem cell transplantation
      (HSCT). We report the successful outcome of cell-mediated cytokine-activated
      immunotherapy in a high-risk pediatric AML patient who relapsed shortly after
      allogeneic HSCT. Donor lymphocyte infusion along with interferon induced a graft
      versus-leukemia effect, presenting as a reversible episode of graft-versus-host
      disease, which led to stable complete donor chimerism and total eradication of
      AML for over 24 months, at the time of this report. The curative potential of
      immunotherapy in hematological malignancies is discussed.

PMID- 19105235
TI  - Mechanisms of gene amplification and evidence of coamplification in drug
      resistant human osteosarcoma cell lines.
AB  - Gene amplification and copy number changes play a pivotal role in malignant
      transformation and progression of human tumor cells by mediating the activation
      of genes and oncogenes, which are involved in many different cellular processes
      including development of drug resistance. Since doxorubicin (DX) and methotrexate
      (MTX) are the two most important drugs for high-grade osteosarcoma (OS)
      treatment, the aim of this study was to identify genes gained or amplified in six
      DX- and eight MTX-resistant variants of the human OS cell lines U-2OS and Saos-2,
      and to get insights into the mechanisms underlying the amplification processes.
      Comparative genomic hybridization techniques identified amplification of MDR1 in
      all six DX-resistant and of DHFR in three MTX-resistant U-2OS variants. In
      addition, progressive gain of MLL was detected in the four U-2OS variants with
      higher resistance levels either to DX or MTX, whereas gain of MYC was found in
      all Saos-2 MTX-resistant variants and the U-2OS variant with the highest
      resistance level to DX. Fluorescent in situ hybridization revealed that MDR1 was
      amplified in U-2OS and Saos-2/DX-resistant variants manifested as homogeneously
      staining regions and double minutes, respectively. In U-2OS/MTX-resistant
      variants, DHFR was amplified in homogeneously staining regions, and was
      coamplified with MLL in relation to the increase of resistance to MTX. Gene
      amplification was associated with gene overexpression, whereas gene gain resulted
      in up-regulated gene expression. These results indicate that resistance to DX and
      MTX in human OS cell lines is a multigenic process involving gene copy number and
      expression changes.

PMID- 19105236
TI  - Papillary and muscle invasive bladder tumors with distinct genomic stability
      profiles have different DNA repair fidelity and KU DNA-binding activities.
AB  - Low-grade noninvasive papillary bladder tumors are genetically stable whereas
      muscle invasive bladder tumors display high levels of chromosomal aberrations. As
      cells deficient for nonhomologous end-joining (NHEJ) pathway components display
      increased genomic instability, we sought to determine the NHEJ repair
      characteristics of bladder tumors and correlate this with tumor stage and grade.
      A panel of 13 human bladder tumors of defined stage and grade were investigated
      for chromosomal aberrations by comparative genomic hybridization and for NHEJ
      repair fidelity and function. Repair assays were conducted with extracts made
      directly from bladder tumor specimens to avoid culture-induced phenotypic
      alterations and selection bias as only a minority of bladder tumors grow in
      culture. Four noninvasive bladder tumors (pTaG2), which were genetically stable,
      repaired a partially incompatible double-strand break (DSB) by NHEJ-dependent
      annealing of termini and fill-in of overhangs with minimal loss of nucleotides.
      In contrast, four muscle invasive bladder cancers (pT2-3G3), which displayed
      gross chromosomal rearrangements, repaired DSBs in an error-prone manner
      involving extensive resection and microhomology association. Four minimally
      invasive bladder cancers (pT1G3) had characteristics of both repair types. Error
      prone repair in bladder tumors correlated with reduced KU DNA-binding and loss of
      TP53 function. In conclusion, there were distinct differences in DSB repair
      between noninvasive papillary tumors and higher stage/grade invasive cancers. End
      joining fidelity correlated with stage and was increasingly error-prone as tumors
      became more invasive and KU binding activity reduced; these changes may underlie
      the different genomic profiles of these tumors.

PMID- 19105237
TI  - The chorionic bump in an ectopic pregnancy.
AB  - The chorionic bump, an irregular, convex bulge of the choriodecidual surface into
      the gestational sac (GS), is a recently described, uncommon abnormality of the
      1st-trimester GS and is associated with a guarded prognosis for early pregnancy.
      The case of this 42-year-old female demonstrates a previously unreported
      relationship: a transvaginal sonographic finding of a chorionic bump associated
      with a spontaneous tubal ectopic pregnancy. This might support the hypothesis
      that the chorionic bump represents a small hematoma that bulges into the GS.

PMID- 19105238
TI  - Prenatal sonographic appearance of truncus arteriosus on wide-band Doppler
      imaging.
AB  - Persistent truncus arteriosus is an uncommon congenital cardiac anomaly. In most
      patients, this condition is not diagnosed prior to birth. We report a case in
      which this uncommon cardiac anomaly was diagnosed prenatally using wide-band
      Doppler imaging. When diagnosing fetal truncus arteriosus, sonologists should
      carefully search for the origin of the main pulmonary artery and for its 2
      branches. Our experience suggests that wide-band Doppler imaging facilitates the
      prenatal diagnosis of truncus arteriosus.

PMID- 19105239
TI  - Treatment of herpesvirus cofactors?

PMID- 19105242
TI  - Nosologic imaging of the brain: segmentation and classification using MRI and
      MRSI.
AB  - A new technique is presented to create nosologic images of the brain based on
      magnetic resonance imaging (MRI) and magnetic resonance spectroscopic imaging
      (MRSI). A nosologic image summarizes the presence of different tissues and
      lesions in a single image by color coding each voxel or pixel according to the
      histopathological class it is assigned to. The proposed technique applies
      advanced methods from image processing as well as pattern recognition to segment
      and classify brain tumors. First, a registered brain atlas and a subject-specific
      abnormal tissue prior, obtained from MRSI data, are used for the segmentation.
      Next, the detected abnormal tissue is classified based on supervised pattern
      recognition methods. Class probabilities are also calculated for the segmented
      abnormal region. Compared to previous approaches, the new framework is more
      flexible and able to better exploit spatial information leading to improved
      nosologic images. The combined scheme offers a new way to produce high-resolution
      nosologic images, representing tumor heterogeneity and class probabilities, which
      may help clinicians in decision making.

PMID- 19105243
TI  - Findings of scientific misconduct.

PMID- 19105245
TI  - New hope for health in South Africa.

PMID- 19105246
TI  - Global food crisis looks set to continue.

PMID- 19105244
TI  - Rapamycin inhibits growth factor-induced cell cycle regulation in pancreatic beta
      cells.
AB  - A progressive decline in islet function is a major obstacle to success of islet
      transplantation. The cause of this decline is islet function is unclear, but
      immunosuppressive agents may contribute. Insulin-like growth factor-I (IGF-I) and
      betacellulin are important for islet cell survival and/or proliferation. In the
      present study, we performed studies of IGF-I and betacellulin on progression of
      islet cells through the cell cycle and the impact of immunosuppressive agents.
      Treatment of INS-1 cells for 24 hours with 20 ng/mL betacellulin or 50 ng/mL IGF
      1 increased cells in S phase by ~2-fold. Treatment of INS-1 cells with IGF-I or
      betacellulin also increased cyclin D1 expression and nuclear exclusion of the
      cyclindependent kinase inhibitors p21(Cip1) and p27(Kip1). In INS-1 cells and
      islets, betacellulin- and IGF-I increased the increase in p70(s6 kinase)
      phosphorylation stimulated by betacellulin- and IGF-I in INS-1 cells. Rapamycin
      also inhibited betacellulin- and IGF-I IN IGF-1 cells. Rapamycin also inhibited
      betacellulin- and IGF-I-induced entry of cells into S phase and 5'-Bromo-2'
      deoxyuridine incorporation as well as the effect of betacellulin and IGF-I on
      cyclin D1 expression and nuclear exclusion of p21(Cip1) and p(27Kip1). Together,
      these data suggest that the effect of betacellulin and IGF-I on islet cell growth
      and proliferation is mediated, in part, via signaling through mammalian target of
      rapamycin. As rapamycin is used to treat islet transplant recipients, these
      results suggest that rapamycin could have deleterious effects on islet
      proliferation and function over time.

PMID- 19105247
TI  - Autonomy and selfishness.

PMID- 19105248
TI  - Patient experiences with MedlinePlus.gov: a survey of internal medicine patients.
AB  - BACKGROUND: In 2004, the American College of Physicians joined with the National
      Library of Medicine in an effort to help patients find reliable health
      information free of commercial bias as the Web site MedlinePlus.gov. The aim of
      this study was to evaluate the usefulness of the MedlinePlus.gov site as
      perceived by patients who were referred to the site by their internist. MATERIALS
      AND METHODS: A 27-item questionnaire developed by the American College of
      Physicians Foundation was distributed between january and May 2005 to a
      convenience sample of 893 adult patient volunteers attending 34 internal medicine
      practices across the United States. RESULTS: The questionnaire revealed that
      although most patients (55%) routinely look up medical information, only 43% had
      used MedlinePlus.gov. Of those who had used the site, 95% were satisfied with the
      information they found there, and 94% said the information they found at
      MedlinePlus.gov would help them make better health decisions. DISCUSSION:
      Patients who used the MedlinePlus.gov site at the recommendation of their
      physician found it to use, informative, and felt it would help them make better
      health decisions. Directing patients to this high quality, noncommercial,
      educational resource online may be an important adjunct to patient education
      efforts by physicians.

PMID- 19105249
TI  - Strategies for optimal disease management, adherence, and outcomes in multiple
      sclerosis patients.

PMID- 19105250
TI  - [Method of pharmacological myocardial preconditioning with halogen-containing
      anesthetics in cardiosurgical patients].
AB  - The purpose of the investigation was to study whether isoflurane and sevoflurane
      might be used for pharmacological myocardial preconditioning (PMP) in patients
      with coronary heart disease during myocardial revascularization on the working
      (Part I) and arrested (Part II) heart and to develop a possible procedure for
      PMP. Part I deals with the study of the effect of PMP with halogen-containing
      anesthetics during myocardial revascularization on the working heart. The study
      included 66 patients who were divided into 4 groups; 1) sevoflurane feeding was
      started just after anesthesia induction and it lasted until some coronary
      arteries were ligated; 2) sevoflurane was fed for 15 min; 3) isoflurane was used;
      4) controls. The markers of myocardial lesion (troponin T, I) were measured and
      the incidence of perioperative myocardial ischemia and needs for inotropic
      support were also analyzed. Part II was dedicated to the study of the effect of
      PMP during myocardial revascularization under extracorporeal circulation (EC).
      The study covered 65 patients who were divided into 4 groups; 1) sevoflurane was
      administered throughout the anesthesia until the aorta was ligated; 2) it was
      used for 15 min before aortic ligation; 3) sevoflurane was employed only to
      induce anesthesia; 4) controls. The variables similar to those in Part I of the
      investigation were chosen to assess the results of this study. The use of
      sevoflurane and isoflurane reduces a risk for myocardial ischemic lesion during
      myocardial revascularization both under EC and on the working heart. Short-term
      (15-min) use of an agent before myocardial ischemia suffices for PMP to develop
      its effect. The effect of PMP has its duration that is 76 min, as shown by our
      findings.

PMID- 19105251
TI  - [Analgesic and opioid-sparing effects of intravenous paracetamol in the early
      period after aortocoronary bypass surgery].
AB  - The study was to evaluate the analgesic and opioid-sparing effect of intravenous
      paracetamol injections in cardiosurgical patients in the early postoperative
      period. Adequate analgesia within the first 12-18 hours of the early
      postoperative period is very important for a good prognosis of the further course
      of pain syndrome and for the reduction of a risk for its progression to its
      chronic form. In early studies, propacetamol lowered morphine use after
      orthopedic and gynecological operations. The efficacy of paracetamol used in
      cardiac surgery has been little studied and the results of the studies are
      conflicting. The randomized, blind, placebo-controlled study included patients
      after aortocoronary bypass surgery, of them 22 patients received paracetamol and
      23 had placebo. The test drug (perfalgan 100 ml or placebo) was intravenously
      injected 30 min before extubation and then every 6 hours within succeeding 18
      hours. The intensity of the pain syndrome was rated by a 5-score verbal scale
      every 2 hours. With pain score of 2 or more, promedol was intramuscularly
      administered in a dose of 10 mg. Inspiratory volume was recorded before
      extubation and the first administration of a drug just after extubation and then
      every 2 hours. The baseline indices did not differ in both groups. Throughout the
      observation, the inspiratory volume was lower in the paracetamol group than in
      the placebo group; however, there was a statistically significant difference (p =
      0.012) in the reduction in the manifestations of the pain syndrome (by 81%) only
      just after tracheal extubation. During this period, inspiratory volume values
      were higher in the paracetamol group; however, a statistically significant (39%)
      difference between the groups in the mean values was obtained only during and 2
      hours after extubation. In the perfalgan group, the mean total use of promedol
      was 36% less than in the placebo-group, which was statistically significant (p =
      0.019). The early postoperative use of paracetamol after myocardial
      revascularization reduces the intake of opioids and diminishes the intensity of
      the pain syndrome within the first hours after extubation, which promotes a
      higher thoracic excursion, as confirmed by a statistically significant increase
      in the maximum inspiratory capacity.

PMID- 19105252
TI  - [Use of loading test to predict intraoperative heart failure in cardiosurgical
      patients].
AB  - The paper deals with the development of a procedure for using loading tests to
      predict the development of intraoperative heart failure in cardiosurgical
      patients. A volumetric loading test (limb elevation) was carried out to assess
      the mechanisms of responsible for the regulation of performance of the heart and
      the efficiency of its work. Cardiac output, end diastolic volume index, and
      ejection fraction were recorded and a hemodynamic response was assessed from
      their changes. Loading tests enabled the authors to identify 3 types of a
      hemodynamic response to a volumetric load. The incidence of postperfusion heart
      failure may be predicted depending on the identified type of a hemodynamic
      response to the volumetric load given at the very beginning of surgery.

PMID- 19105253
TI  - [Use of a potassium and magnesium asparaginate solution to maintain the balance
      of potassium and magnesium during cardiosurgical interventions under
      extracorporeal circulation].
AB  - The study included 42 patients with coronary heart disease operated on the
      coronary arteries. A potassium and magnesium asparaginate (PMA) solution, 450
      1000 ml, was injected in 30 patients for 5-7 hours; other crystalloid solutions
      was used in a control group (n = 12). The concentrations of potassium and
      magnesium were measured prior to surgery, following initial anesthesia, before
      and after extracorporeal circulation (EC). The measurements suggested a
      significant potassium and magnesium intake at surgery under EC. The use of PMA
      solution showed its advantage in stabilizing the study electrolytes at the main
      surgical stages. Inclusion of PMA into infusion therapy considerably reduced a
      need for an additional use of concentrated KCl solution to maintain potassium at
      the preoperative level. Of particular importance was the use of PMA to maintain
      magnesium that was held in the upper normal range throughout the operation, as
      shown by both the median values and an individual analysis. When PLA was not
      administered, the mean concentration of magnesium was consistent with that in the
      lower normal electrolyte range and 50% patients developed hypomagnesemia. The
      comparative analysis of the clinical course after EC in both groups of patients
      with different levels of magnesium was indicative of the better status of some
      hemostatic parameters with the level of magnesium being maintained in the upper
      normal range.

PMID- 19105255
TI  - [Parenteral nutrition in the therapeutic treatment of chylothorax after surgical
      correction of aortic coarctation].

PMID- 19105254
TI  - [Left ventricular dysfunctions after correction of aortic stenosis].
AB  - The purpose of the investigation was to study central hemodynamics and left
      ventricular function in low cardiac output after correction of aortic stenosis.
      The study included 34 patients (28 males and 6 females) aged 59. 7+/-1.5 years,
      surged with cardiopulmonary bypass (CPB). Low cardiac output was detected in all
      cases in the post-CPB period. Inotropic support with dopamine and/or dobutamine
      was effective in 47% of the patients (Group 1) and ineffective in 53% (Group 2).
      There were no statistically significant differences in cardiac index and
      pulmonary wedge pressure between the groups. Group 1 patients had ultrasound
      signs of left ventricular systolic dysfunction (low left ventricular ejection
      fraction and larger left ventricular systolic and diastolic areas in the
      transgastric position). Group 2 patients had ultrasound signs of left ventricular
      diastolic dysfunction (high left ventricular ejection fraction and smaller left
      ventricular systolic and diastolic areas). beta-blockers were used in 10 patients
      from Group 2. Central hemodynamics and left ventricular function normalized in
      all these cases. It is concluded that it is possible to recognize left
      ventricular dysfunctions in low cardiac output after aortic valve replacement
      with transesophageal echocardiography. Inotropic support is effective in only
      patients with left ventricular systolic dysfunction. Patients with left
      ventricular diastolic dysfunction should receive beta-blockers.

PMID- 19105256
TI  - [Use of the epiglottic airway I-gel during anesthetic maintenance: first clinical
      impressions].
AB  - The paper gives a concise account of the evolution of epiglottic airways and the
      emergence of the new product of this class--I-gel (Intersurgical, United
      Kingdom). It outlines the structural features of I-gel and the authors'
      experience in using the latter to maintain airway patency during anesthetic
      maintenance in 34 patients. Based on a review of the scanty data available in the
      literature on this airway and their clinical experience, the authors come to the
      conclusion that there is a great variety of I-gel inherent positive
      characteristics that make this airway highly promising for the needs of current
      anesthetic maintenance and, possibly, resuscitative care. The authors consider it
      expedient to expand the use of I-gel to specify the evaluation of its efficiency
      and competitive capacity of the epiglottic airways that have already well shown
      themselves.

PMID- 19105257
TI  - [Anesthetic maintenance of renal transplantation in children].
AB  - For many children with severe renal excretory dysfunction, renal transplantation
      is the sole method of life prolongation. The purpose of the investigation was to
      analyze the specific features of anesthetic maintenance of transplantation of
      related and cadaver kidney at 1 to 5 years. The investigation involved a detailed
      analysis of the specific features of 101 anesthesias made in children aged 1 to
      16 years (mean 9.6+/-4.87 years) during transplantation of kidneys from corpses
      and apparently healthy relatives. The duration of surgery and anesthesia was
      5.6+/-1.00 and 7.6+/-1.42 hours, respectively. Operations were made under
      balanced general anesthesia using a low-flow inhalational isoflurane or
      sevoflurane (0.5-2.0 MAC) technology. After inclusion of a graft into the
      bloodstream, a plasmapheresis procedure was initiated in 1-1.5 circulating blood
      volumes. All the children underwent invasive hemodynamic monitoring: the radial
      artery and internal jugular vein were catheterized. In 19 cases, the pulmonary
      artery was catheterized using a Swan-Ganz catheter. In children, the initial
      period of anesthesia during renal transplantation was marked by a drastic
      hemodynamic instability tended for hypotension and significant tachycardia in the
      presence of marked hypovolemia (central venous pressure = 0+/-2.0 mm Hg). The
      major component of infusion therapy was freshly frozen plasma (up to 50% of the
      volume). Inclusion of a cold renal graft into systemic circulation and washout of
      residues of preservative solution and necrobiolysis products from it were
      accompanied by a 0.5-1.3 degrees C temperature reduction and progression of
      metabolic acidosis. Safe and successful anesthetic maintenance of renal
      transplantation in children requires an obligatory informative invasive
      hemodynamic monitoring, continuous laboratory screening, and knowledge of stage
      specific features. Continuous plasmapheresis by means of a plasma filter is
      preferred.

PMID- 19105258
TI  - [Does pre-emptive analgesia really pre-empt?].
AB  - The paper discusses the theoretical background and practical rationale for a
      concept of pre-emptive analgesia. It gives the results of studying the efficacy
      of lornoxicam that outstrips the infliction of a surgical injury in different
      anesthesia modes (combined total and intravenous combined multicomponent
      anesthesia with epidural block). A hundred thirty-seven patients who had
      undergone laparoscopic cholecystectomies (Group 1) and expanded interventions for
      colorectal cancer (Group 2) were examined. The examination provided no evidence
      for the efficiency of pre-emptive analgesia with lornoxicam during perioperative
      anesthesia in patients undergone moderately and highly traumatic abdominal
      interventions.

PMID- 19105259
TI  - [Grounds for the inclusion of vaccination against cervical cancer within the
      National Immunisation Programme].

PMID- 19105260
TI  - Disagrees with editorial on assistants.

PMID- 19105261
TI  - [A 78-year-old woman with upper abdominal pain].

PMID- 19105262
TI  - [Surgery of visceral arteries].

PMID- 19105263
TI  - [Young woman in need of a pacemaker].

PMID- 19105264
TI  - [Guidelines should be followed as a rule].

PMID- 19105265
TI  - Medicaid financing: how the FMAP formula works and why it falls short.
AB  - Medicaid costs for health and long-term care services for low-income individuals
      are substantial. As a result, each state's "match rate," or federal medical
      assistance percentage (FMAP), which determines the share of Medicaid benefit
      costs the federal government pays, has enormous implications for state budgets
      and state economies, as well as for Medicaid beneficiaries and providers. Shifts
      in the FMAP from year to year, even minor ones, can mean the gain or loss of tens
      or hundreds of millions of federal matching dollars, depending on the size of the
      state's Medicaid program. This paper explains the FMAP formula, examines the
      limitations of this method for distributing federal Medicaid financing, and
      highlights options to address the formula's shortcomings.

PMID- 19105266
TI  - The relative (in)efficiency of the U.S. health care system.

PMID- 19105267
TI  - No God--and no abortions.

PMID- 19105268
TI  - [Determination of strength of femoral neck in patients with hip fracture].
AB  - OBJECTIVE: To study the relationship between the hip fracture and osteoporosis of
      the aged. METHODS: The strength of contralateral unfractured proximal femur
      (Singh index) in 80 patients with hip fractures from 1998 to 2003 were collected,
      and the patients' age were all over 50 years. At the same time, the strength of
      proximal femur of 90 patients without fractures were also measured, and the
      figures were analyzed. RESULTS: The results showed that the fractures of proximal
      femur was closely related to osteoporosis in 50-60 age group and 61-70 age group
      (P<0.01). The relationship was not obvious when the age was over 70 (P>0.05).
      CONCLUSION: The strength of proximal femur in patients with hip fracture was
      obvious decreased. The Singh index of proximal femur can be helpful in
      forecasting the possibility of proximal femur fracture.

PMID- 19105269
TI  - [Controlled clinical trials on the pathological expressions of VEGF in patients
      with active ankylosing spondylitis].
AB  - OBJECTIVE: To investigate the pathological expression and significance of VEGF in
      patients with active ankylosing spondylitis. METHODS: The expression of VEGF in
      the synovial tissues of cacroiliac joint of patients with active AS was detected
      by using in situ hybridization and the results were compared with those in the
      patients with pelvic fracture using image analysis system. RESULTS: The positive
      expressions of VEGF in the synovial tissues of cacroiliac joint of patients with
      active AS were stronger than those in the control group (P<0.01). CONCLUSION:
      VEGF are important factors in patients with active AS. They are tightly
      correlated with the process of osteoclasia and pathological new bone formation in
      the cacroiliac joint of patients with active AS. If we can reduce the expressions
      of VEGF in the patients with active AS, the process of osteoclasia and
      pathological new bone formation will be interrupted and this provides a new
      strategy for the treatment of ankylosing spondylitis.

PMID- 19105270
TI  - [Controlled clinical trials on the effects of Chinese traditional medicine for
      the treatment of osteoarthritis of knee joint at early stage and its MRI
      changes].
AB  - OBJECTIVE: To investigate the effects of Chinese traditional medicine for the
      treatment of osteoarthritis of knee joint at early stage, as well as to observe
      the changes of articular cartilage in MRI before and after the treatment.
      METHODS: Sixty patients were divided into two groups according to Doll's law, 32
      patients in the treatment group (6 male and 26 female, with an average age of
      52.2 years, ranging from 43 to 65 years, 40 joints), 28 patients in the control
      group (5 male and 23 female, with an average age of 54.4 years, ranging from 42
      to 65 years, 33 joints). The patients in the test group were given Chinese
      traditional medicine orally, and patients in the control group were given
      celecoxib and the glucosamine hydrochloride orally for three months. MR scan and
      ISOA score were given respectively before and after treatment. After the
      treatment, the articular cartilage changes of the weight bearing area were
      observed to evaluate the therapeutic effects. RESULTS: All the patients were
      followed up ranging from 13 to 17 months, with an average of 15.3 months.
      According to MRI evaluation, 15 joints got an excellent result, and 17 joints got
      a good result in the treatment group, the total excellent and good rate was
      80.0%; and in the control group, above data were 8, 11 and 57.6% respectively.
      The average ISOA score of the treatment group after treatment was 0.35 +/- 0.16,
      and in the control group was 3.68 +/- 0.18. There was significant differences
      between the two groups of ISOA score (t = 6.94, P<0.05). CONCLUSION: Chinese
      traditional medicine can significantly alleviate or inhibit the cartilage
      degeneration of knee osteoarthritis at early stage and improve joint function. It
      had significant clinical effects.

PMID- 19105271
TI  - [Total hip replacement in the treatment of severe deformity of the hip caused by
      advanced ankylosing spondylitis].
AB  - OBJECTIVE: To evaluate the clinical results of the total hip replacement in the
      treatment of severe deformity of the hip joint caused by advanced ankylosing
      spondylitis. METHODS: Forty-five hips with severely deformities in 33 patients
      suffered from advanced ankylosing spondylitis treated by total hip replacement
      were followed-up from 1992 to 2005 in our department. The pain index, deformity
      angle, range of motion of the joint, changes of weight baring capacity of a
      single leg, and the postoperative complications were compared and analysed in
      this study. RESULTS: The pain was complete released in 27 hips after surgery; the
      average pain index decreased 1 grade. The angle of flexion deformity of hip
      decreased by 44.17 degrees averagely. The average range of motion of the hip
      improved 58.4 degrees. Thirty-one operated hips could bare weight itself. Twenty
      two hips occurred prosthesis Sinking of the femur head prosthesis occurred in 22
      hips. The sciatic nerve was contused in one case because of violent reduction
      after the installation of prosthesis, and recovered in 8 months. CONCLUSION: The
      midterm clinical results of total hip replacement in the treatment of severe
      deformity of hip caused by advanced ankylosing spondylitis is satisfactory.

PMID- 19105272
TI  - [Clinical application of the combination of postural reduction and kyphoplasty
      for traumatic thoracolumbar spine fractures].
AB  - OBJECTIVE: To determine the efficacy and feasibility of the combination of
      postural reduction and percutaneous kyphoplasty for traumatic thoracolumbar spine
      fractures. METHODS: Thirty-seven patients with single level traumatic
      thoracolumbar spine fractures were included in this study. There are 28 males and
      9 females, with an average age of 48 years (range 24 to 79 years). Patients were
      treated with postural reduction and then percutaneous vertebroplasty with Calcium
      Phosphate Cement (CPC) were performed on the fractured vertebra. The results were
      quantitatively evaluated, according to the concept of estimated vertebral height
      loss and kyphotic angle of the vertebral fractures by preoperative and
      postoperative plain standing lateral radiographs. Visual analog scale (VAS) and
      the fracture vertebra shape changes were recorded. RESULTS: Patients were
      followed up for 9 to 24 months (average 13 months), pain was significantly
      relieved compared with the preoperative, VAS was reduced averagely from 7.6 +/-
      2.5 to 1.8 +/- 1.5, the anterior and middle vertebral height was restored and
      kyphotic angle was corrected. During the period of follow up, outcomes were
      satisfactory, without notable correction loss. CONCLUSION: If the indications are
      correctly handled, the combination of postural reduction and percutaneous
      kyphoplasty for the treatment of traumatic thoracolumbar spine fractures can
      provide significant pain relieve and restore the vertebral height and kyphotic
      angle.

PMID- 19105273
TI  - [Effect of Chinese herb medicine compound on bone loss in rats under 3 weeks
      simulated weightlessness: preliminary study].
AB  - OBJECTIVE: To investigate the effect of Chinese herb medicine compound on bone
      lose in rats under 3 weeks simulated weightlessness, and to observe the
      synergistic action of other ingredients in the compound on calcium. METHODS:
      Thirty male Wistar rats were divided into 3 groups: control group, tail-suspend
      group, tail-suspend and medicine group which took Chinese herb medicine compound
      (contains Radix Rehmanniae Praeparata, Radix Achyranthis Bidentatae, Radix
      Astragali, Radix Angelicae Sinensis, Concha Ostreae prepared by acetic acid) by
      gastric administration. After 3 weeks simulated weightlessness, serum calcium
      (Ca), phosphorus (P), bone mineral density (BMD) and content (BMC), bone
      mechanical properties (MEC) were observed. RESULTS: At the end of the experiment,
      serum Ca and P increased significantly (P<0.01), BMD and BMC of posterior body
      decreased significantly (P< 0.01) in tail suspend rats, compared with in the
      control group. In rats of tail suspended and medicine group, the increase degree
      of serum Ca and P were smaller, BMD and BMC of posterior body increased
      significantly (P<0.01 or 0.05), and MEC also tend to increase. CONCLUSION: Bone
      mass of posterior body lose significantly, with mechanical property significantly
      decrease in rats after 3 weeks simulated weightlessness. Chinese herb medicine
      compound is effective to prevent the change of bone. Simple calcium supplement
      can not prevent simulated weightlessness induced bone loss, therefore other
      ingredients in the compound may perform synergistic action to calcium (Concha
      Ostreae prepared by acetic acid).

PMID- 19105274
TI  - [Effects of rhizoma paridis total saponins on levels of cytokines in blood serum
      of two-hit rat model induced by multiple fractures and lipopolysaccharide].
AB  - OBJECTIVE: To investigate the effect of rhizoma paridis total saponins(RPTS)on
      the levels of tumor necrosis factor alpha (TNF-alpha), interleukin-1 beta (IL-1
      beta) and interleukin-6 (IL-6) in blood serum of two-hit rat model induced by
      multiple fractures and lipopolysaccharide. METHODS: Sixty-eight Wistar rats were
      randomly divided into five groups. The models were made in four groups (expect
      the blank control group) in accordance with the standard of two-hit animal model
      induced by multiple fractures and lipopolysaccharide. At 1 hour after models
      made,the rats in RPTS groups were given rhizoma paridis total saponins with
      different concentrations by intragastric administration. Six hours later, the
      concentrations of TNF-alpha, IL-1 beta and IL-6 in the blood serum of all rats
      were detected by ELISA (enzyme linked immunosorbent assay). RESULTS: The
      concentrations of TNF-alpha, IL-1 beta and IL-6 in blood serum of rats in the
      model group were remarkably higher than those in the blank control group
      (P<0.001), and these in the RPTS groups were remarkably lower than those in the
      model group (P<0001). CONCLUSION: RPTS can decrease the levels of TNF-alpha and
      IL-6 and IL-1 beta in the blood serum of rats subjected to two-hit induced by
      multiple fractures and lipopolysaccharide.

PMID- 19105275
TI  - [Experimental study on the treatment of serious soft tissue injuries with
      strengthening the spleen and replenishing qi].
AB  - OBJECTIVE: To study the effects of Chinese drugs based on strengthening the
      spleen and replenishing qi treatment rule on neoformative capillaries and
      fibroblast during the soft tissue repair after serious trauma in rats, so as to
      explore the biological basis of the TCM theory "the spleen dominate extremities
      and muscles" applied to the treatment of soft tissue injuries. METHODS: The model
      rats were established by bleeding from femoral artery and lancing method, and the
      rats were randomly divided into the control group, strengthening the spleen group
      and activating blood and resolving stasis group. The samples were got from the
      tissue of the wounded area at the 5th, 10th and 15th days after oral
      administration of the traditional Chinese medicine. After fixation and section,
      the tissues were stained by CD31 and PCNA staining. The amount of the capillaries
      and fibroblasts in the tissue of the wounded area were observed through multi
      purpose microscope (ZEISS Axioskop2). Quantitative analysis was carried out on
      Image-ProPlus image analyzer. RESULTS: The amount of the capillaries and
      fibroblasts in the wounded tissue in the strengthening the spleen group were
      larger than that in the control group at the 5th, 10th and 15th day. And the
      proliferation speed of capillaries and fibroblasts was faster than those in the
      control group or the activating blood and resolving stasis group. CONCLUSION: The
      Chinese drugs according to strengthening the spleen and replenishing qi treatment
      rule were effective to promote growth of the granulation tissue and facilitate
      healing of the wounded area. And it has better effect than the treatment of
      promoting blood circulation and removing stasis.

PMID- 19105276
TI  - [Effects of Shibao Powder on promoting the expression of b-FGF and TGF-beta 1, in
      the repair of soft tissue injuries].
AB  - OBJECTIVE: To study the effects of Shibao Powder on the expression of b-FGF and
      TGF-beta 1 in granulation tissues of rabbit models with soft tissue injuries, so
      as to explore mechanism of external Chinese drugs for repairing of soft tissues
      in molecular levels. METHODS: The rabbit models were established by classical
      method of full-thickness skin wounds. After 8% sodium sulfide was used and
      routine disinfection completed, intra-peritoneal anaesthesia was adopted. The
      skin was cut to expose gastrocnemius muscle, and imcomplete sharp dissection was
      made near the tendon insertion. The length of the incision was 0.8 cm and the
      width was 0.4 cm. The rabbits in the experimental group were treated with spread
      of Shibao Powder at the wound; the rabbits in clean group were treated with
      routine dressing changes and disinfection; and the rabbits in the control group
      were treated with dressing changes only. The granulation tissues in different
      stages were collected and observed with high power microscope. The expression of
      Transforming Growth Factor-beta 1 (TGF-beta 1) protein and b-FGF protein in wound
      tissues were detected using StreptA-ridin-Biotin-Complex (SABC) method. RESULTS:
      The results showed that the expression of b-FGF protein had significant
      differences among 3 groups at the 6th day after trauma (P<0.05). The TGF-beta 1
      protein expression also had significant differences among 3 groups at the 10th
      and 14th days after trauma (P<0.05). At the same time, the growth states of
      granulation tissues had difference among 3 groups at the same trauma stage, and
      within the same group among different trauma stages. CONCLUSION: This
      experimental study shows that Shibao Powder is effective to promote the repair of
      soft tissues after trauma by stimulating production of endogenous growth factor
      from cells in wound.

PMID- 19105277
TI  - [Application of the internal fixation of posterior fibula plate for the treatment
      of ankle fractures].
AB  - OBJECTIVE: To explore a new method for the treatment of ankle joint fractures,
      and to evaluate its therapeutic effects. METHODS: Among 42 patients with ankle
      joint fractures, 34 patients had complete data for analysis, 19 patients were
      male and 15 patients were female, ranging in age from 21 to 61 years, with an
      average of 37 years. According to Weber-AO classification, there are 28 patients
      of B-type and 6 patients of C-type. The Baird and Jackson Rating System was used
      to evaluate therapeutic effects, and the relationship between the final function
      and fracture type, fracture fixation and, the time of functional training after
      operation were analyzed. Thirty-four patients with ankle joint fractures of B and
      C type were treated with internal fixation of posterior fibula plate to avoid
      injury of articular facet by the nails. The patients combined with the fractures
      of posterior malleolus were treated with fixation of both fibula and posterior
      malleolus through the same incision. RESULTS: All the patients were followed up
      ranging from 1.2 to 3.2 years, with an average of 1.8 years. According to
      evaluation criterion, 24 patients got an excellent result, 6 good and 4 fair, the
      excellent and good rate was 88.2%. CONCLUSION: The internal fixation of posterior
      fibula plate, as a treatment for ankle joint fractures, successfully avoids the
      injury of articular facet by the nails. Not only does it enhance the pullout
      strength of the nails, but it is able to treat the fracture of lateral malleolus
      and posterior malleolus with a single incision. It has provided a new way for the
      treatment of ankle fractures.

PMID- 19105278
TI  - [Surgical treatment for posterior hip dislocations complicated with fractures of
      femoral head and acetabulum].
AB  - OBJECTIVE: To explore the effectiveness and prognosis on surgical treatment of
      posterior hip dislocations complicated with fractures of femoral head and
      acetabulum. METHODS: Seventeen patients with posterior hip dislocations
      complicated with fractures of femoral head and acetabulum were reviewed in the
      study. All the patients were treated with manual reduction within 12 hours after
      injury. CT location was used before operation. Absorbable screw fixation was
      performed for the femoral head fractures, while plate fixation or resection was
      performed for acetabular fractures. RESULTS: All the patients got bony union
      within 6 months after operation without femoral head necrosis. Evaluate joint
      function according to Modifie Daobigne and Postal clinical classification
      criteria, 8 patients got an excellent result, 7 good and 2 fair. The excellent
      and good rate was 88.2%. CONCLUSION: Surgical treatment can have a satisfactory
      prognosis for patient with posterior femoral head and acetabulum.

PMID- 19105279
TI  - [Surgical treatment of acetabular posterior wall fractures].
AB  - OBJECTIVE: To analyze the clinical effect of acetabular posterior wall fractures
      with reconstruction plate internal fixation. METHODS: From January 2001 to
      January 2006, 45 cases were studied retrospectively including, 31 males and 14
      females. The age ranged from 19 to 68 years, mean 37.6 years. All patients of
      acetabular posterior wall fractures were treated by open reduction and internal
      fixation with reconstruction plate. All patients were reviewed retrospectively.
      All patients were treated with the Kocher-Langenbeck approach. RESULTS: Forty
      five patients were followed up for 12 to 48 months, averaged 26 months. By
      Matta's X-ray reduction criteria, there were 38 cases of anatomical reduction, 7
      cases of satisfactory. By modified d'Aubigne clinical evaluation criteria, the
      clinical results were excellent in 30 cases, good in 10 cases and fair in 5
      cases, excellent and good rate of clinical results was 88.9%. There were no
      infection and non-union. The complications included traumatic osteoarthritis in
      4, aseptic necrosis of the femoral head in 2, heterotopic osteogenesis in 2 and
      deep venous thromboembolism in 1. CONCLUSION: Fractures of acetabular posterior
      wall with reconstruction plate internal fixation can gain good clinical results.
      The quality of fracture reduction, the time to surgery after injury, experience
      of surgical operation and the degree of fracture comminution are the factors
      influencing the operative results of posterior wall fractures of the acetabulum.

PMID- 19105280
TI  - [Total hip arthroplasty for degeneration of infected hip: a report of 7 cases].
AB  - OBJECTIVE: To evaluate indications and clinical results of total hip
      arthroplasties for degenerative hips with history of infection. METHODS: Seven
      cases of degenerative hip with history of infection underwent primary total hip
      arthroplasties, which involved 5 males and 2 females, with an average age of 45.8
      years (range, 30 to 65 years). The quiescent period of infection were more than
      10 years in all hips. According to Kim classification, 3 cases were of type I,
      and 4 of type II. The method to exclude active infection at the site of
      degenerative hips preoperatively was combination of physical examination,
      erythrocyte sedimentation rate and C-reactive protein level. The lateral incision
      was adopted in all cases, and all prosthesis were cementless. The clinical
      results of affected hips were assessed according to Harris hip score. RESULTS:
      The follow-up was performed with the mean duration of 33.5 months (range, 21 to
      44 months). No recurrence of infection, damage of nerve function or deep vein
      thrombosis of lower extremities occurred in all cases. The mean Harris hip scores
      improved from 44.5 points preoperatively to 84 points at the latest follow-up. No
      aseptic loosening of prosthesis or periprosthetic osteolysis were found at the
      latest follow-up. CONCLUSION: Total hip arthroplasties has good short term
      results for degenerative hips with history of infection. It is important to
      select indicated cases and rule out the possibility of active infection.

PMID- 19105281
TI  - [Pedicle lag screw for the treatment of indicated Hangman fractures].
AB  - OBJECTIVE: To define the indication of C2 pedicle lag screw to treat Hangman
      fractures and evaluate its results. METHODS: Twenty-eight patients with Hangman
      fractures were enrolled from July 2003 to June 2007. Six, 17 and 5 patients
      classified as type I , II and IIa injuries respectively according to Levine
      Edwards classification and graded as D spinal injury in 3 cases and E in 7 cases
      according to Frankel scale. The entry points of screws were located at middle
      point of lateral mass. The direction of screw is determined based on the
      direction of the medial and superior border of C2 pedicle, usually 25 degrees to
      30 degrees cephalad to the transverse plane and 30 degrees to 35 degrees medial
      to the sagittal plane. The length of screws range from 24 to 30 mm. RESULTS:
      There were no vertebra artery injuries or other complications during the
      operation. A mean follow-up time was 20 months (4 to 48 months). All cases gained
      bony union at the 6th postoperative month with complete neurological function
      recovery. The range of neck rotation was restored normal without cervicle spinal
      instability and lag screws loosing found. CONCLUSION: Single segmental pedicle
      lag screw internal fixation provides instantly stability to Hangman fracture and
      scarcely affects the physiological functions of upper cervicle spine. With
      appropriate indications of the techniques should be reducible Hangman fracture.

PMID- 19105282
TI  - [Pemberton acetabuloplasty for treating the developmental dislocation of hip
      joint].
AB  - OBJECTIVE: To study advantages of Pemberton acetabuloplasty for the treatment of
      developmental dislocation of hip joint. METHODS: Among 106 children (116 hips)
      with development dislocation of hip joint treated by Pemberton acetabuloplasty,
      19 patients (29 hips) were boy, and 87 patients (87 hips) were girl, 46 hips were
      left side, 50 hips were right side and 20 hips were double side, ranging in age
      from 18 months to 13 years, with an average of 7 years and 3 months. All the 116
      hips were treated with Pemberton acetabuloplasty, or "complete operation", which
      included the cutting of adductor and iliopsoas, Pemberton acetabuloplasty
      combined with subtrochanteric femoral shortening and rotation osteotomy. Among
      the hips, 95 hips were treated with simple Pemberton acetabuloplasty, and the
      other 21 hips were treated with complete operation. All the patients with
      bilateral developmental dislocation of hip joint were performed the operation at
      one side firstly, and one year later the other side were performed and the plate
      fixation in the first operation were removed. RESULTS: All the patients were
      followed-up ranging from 2 to 10 years, with an average of 6 years. According to
      Muller and Seddon's evaluation criteria, 67 hips got an excellent result, 34
      good, 10 fair and 5 bad, the excellent and good rate was 87%. CONCLUSION:
      Pemberton acetabuloplasty is suitable for the treatment of developmental
      dislocation of hip joint in children at different ages, and the therapeutic
      effects are good.

PMID- 19105283
TI  - [Comparative study on the clinical results of locking proximal humerus plate
      (LPHP) and traditional plates in the treatment of proximal humerus fractures in
      the young and middle-aged patients].

PMID- 19105284
TI  - [Percutaneous pinning internal fixation for the treatment of old distal radius
      fractures].

PMID- 19105285
TI  - [Retrograde interlocking intramedullary nail in treatment of humeral shaft
      fracture complicated with radial nerve injury].

PMID- 19105286
TI  - [Cannulated screw internal fixation for the treatment of femoral neck fractures:
      a report of 135 cases].

PMID- 19105287
TI  - [Barton fractures treated with closed reduction and plaster stabilization].

PMID- 19105288
TI  - [Compressive cannulated screw for the treatmeng of femoral neck fracture].

PMID- 19105289
TI  - [Medial humeral condylar fractures: a report of 5 cases].

PMID- 19105290
TI  - [Treatment of recrudescent hallucis onychocryptosis in female using resection of
      partial onyx and hyponychium].

PMID- 19105291
TI  - [Clinical analysis of surgical treatment of tibial plateau fracture with internal
      fixation].

PMID- 19105292
TI  - [Violent manipulation to release adhesion inducing condylar fracture of femur and
      malunion: a report of 1 case].

PMID- 19105293
TI  - [Neotype spine exteral fixator development and clinical application of micor
      invasive therapy for thoracolumbar fractures].

PMID- 19105294
TI  - [Microsurgery treatment for major arterial closed injuries of the extremities].

PMID- 19105295
TI  - [Bone setting manipulation for the treatment of anterior dislocation of shoulder
      joint].

PMID- 19105296
TI  - [Experience of treatment for twenty-nine patients of the atlanto-axial rotatory
      subluxation].

PMID- 19105297
TI  - [Clinical observation for curative effects of epidural injection of Mailuoning
      for the treatment of lumbar intervertebral disc herniation].

PMID- 19105298
TI  - [Design and clinical application of a guiding instrument for anteversion of
      femoral neck].

PMID- 19105299
TI  - [Analysis on the cause of missdiagnosis of metatarsus fractures].

PMID- 19105300
TI  - [Prevention and management of complications associated with iliac crest bone
      graft].

PMID- 19105301
TI  - [Analysis on the causes of misdiagnosis of gouty arthritis].

PMID- 19105302
TI  - [Manipulative treatment of derangement of patellofemoral joint].

PMID- 19105303
TI  - [Sleeve fracture of the upper pole of patella in children: a report of 1 case].

PMID- 19105304
TI  - [Research development of the induced animal model of osteoarthritis].
AB  - Osteoarthritis (OA) is a retrogressive arthrosis of which incidence rate
      increased obviously with the age. Accompany with the aging of the population, the
      incidence of this disease appeares an upward trend significantly. The etiology
      and pathogenesis of AO is not very clear at present, so it's important to
      establish animal models for discussing the pathogenesis of AO and searching
      reasonable ways to diagnose and treat. The induced animal model is used more
      commonly, it includes non-operation ways and operation ways, the former includes
      drug injection, joint immobilization, transarticular impact, etc.; the latter
      includes destroy the stability of joint, change the stress of joint, snick on
      condylofemur etc. This article makes a brief review on those questions, looks
      forward to providing some reference on choosing OA animal model correctly and
      reasonably.

PMID- 19105305
TI  - [Diagnosis value of biological markers CTX-II in osteoarthritis].
AB  - It is very difficult to diagnosis osteoarthritis in the early stage, due to the
      slow development of the disease, no symptoms occures, and no X-ray findings in
      the early stage, it is difficult to early diagnosis with the traditional
      diagnostic methods, resulting in the poor treatment outcome, and even some
      patients develop joint deformity, activity limitation, and must take an
      operation, it brought great pain and heavy financial burden to patients. How to
      early diagnosis of articular cartilage injury become difficult now. Some scholars
      suggest that to those suspected patients, the arthroscopic diagnosis must be
      taken. Although the small trauma and quick recover, the method of operation has
      trauma, not only increase the suffering of the patients, but the treatment is
      very expensive, make the patients finch. A large number of domestic and foreign
      scholars to study patients with OA to find the ideal fluid biological markers
      (BM) to reflect articular cartilage metabolism, and revealed disease activity or
      prognosis. The CTX-II can reflect degradation of the articular cartilage.

PMID- 19105307
TI  - Inside the shopping brain.

PMID- 19105306
TI  - Tracking a new generation.

PMID- 19105308
TI  - The abortion wars get technical.

PMID- 19105309
TI  - Never say die.

PMID- 19105310
TI  - Will stem cells finally deliver?

PMID- 19105311
TI  - New era, new worry.

PMID- 19105312
TI  - A new grip on life.

PMID- 19105313
TI  - Heroin hits the suburbs-hard. A sad trail of abuse is spreading beyond the
      Northeast's inner cities.

PMID- 19105314
TI  - A spreading appreciation for the benefits of hospice care. Putting terminally ill
      patients at ease in their final months.

PMID- 19105315
TI  - A breast cancer conundrum.

PMID- 19105316
TI  - Artist's work honours tradition of healing in the military.

PMID- 19105318
TI  - CNA's past presidents offer their perspectives on the role.

PMID- 19105317
TI  - These nurses have wings! Fort McMurray's Flying Hospital is the only one of its
      kind in Canada.1984.

PMID- 19105319
TI  - CNA's role in protection of the public reflects changing times.

PMID- 19105320
TI  - Giving nurses a voice in patient safety.

PMID- 19105321
TI  - A century of research in nursing human resources.

PMID- 19105322
TI  - Community health nursing research: a retrospective.

PMID- 19105323
TI  - Roles, research & resilience: the evolution of advanced practice nursing.

PMID- 19105324
TI  - Multiplex PCR for the detection of urogenital pathogens in mothers and newborns.
AB  - Two duplex PCR assays were established for the detection of C. trachomatis (Ct),
      N. gonorrhoeae (GC), M. hominis (Mh), and U. urealyticum (Uu). These assays were
      used on clinical specimens obtained from women with Premature Rupture of Membrane
      or Post Partum Fever, from preterm infants, as well as from women with uneventful
      pregnancies and their babies delivered vaginally at term. The analytical
      sensitivity of the duplex PCR assays with internal controls incorporated is 7.0,
      19.0, 5x10(3) and 7x10(2) genome copies per reaction for Ct, GC, Mh and Uu
      respectively. Specificity was demonstrated by the amplification of only target
      DNA in the presence of other organisms. Among 40 women with normal, at term,
      deliveries, there were 6 positives for Ct, 2 for GC and 1 for Uu. None of these
      women had signs of genital tract infection. The Mh/Uu PCR was positive in 11 of
      40 PROM cases, with 7 women positive for Uu, 2 for Mh and 2 others for both
      organisms. Of 40 blood cultures taken from post-partum maternal infections, 6
      were positive for Ct and 1 for Mh. Respiratory secretions from 30 premature
      neonates yielded 5 positives for Uu and one each for Mh and Ct. In contrast,
      there was only 1 positive result (for Mh) in 30 mature neonates. With 1
      exception, all mycoplasma and ureaplasma positives were confirmed by culture and
      the concordance between paired tracheal aspirates and nasopharyngeal swabs from
      neonates was 96.7%. These results show the potential use of the duplex PCR assays
      for the diagnosis of maternal and neonatal disease caused by the four urogenital
      pathogens.

PMID- 19105325
TI  - A study on PCR-RFLP of Giardia duodenalis in Malaysia.
AB  - Giardia duodenalis causes diarrhoea and malabsorption. The objectives of the
      study were to detect local isolates of G. doudenalis by polymerase chain reaction
      (PCR) and to determine their restriction fragment length polymorphisms (RFLP). G.
      doudenalis isolated from stools of patients from Hospital Orang Asli Gombak were
      cultured axenically using TYI-S-33 medium with 10% foetal calf serum. The
      commercially designed primer-pair 432/433 was used to amplify a 0.52 kb segment
      known to encode the homologous cysteine-rich trophozoite surface antigen (tsp11
      and tsa417). Results showed that the primer-pair 432/433 could amplify the target
      region of the local isolates. RFLP study on the identical isolates showed that
      all the restriction enzymes tested ( HindIII, ClaI, PstI and Kpn) gave a banding
      pattern similar to that of the WB strain a reference pathogenic strain from
      human. The reference pathogenic strain were commercially obtained from the
      American Type Culture Collection (ATCC).

PMID- 19105326
TI  - Telomerase activation in neoplastic cell immortalization and tumour progression.
AB  - The unique ability of tumour cells to proliferate indefinitely is crucial to
      neoplastic progression as it allows these cells to express the aggressive
      properties of cancer without the censure of physiological ageing. This is in
      contrast to normal somatic cells which are subject to a "mitotic clock," a
      phenomenon that has been linked to telomeric shortening after each round of cell
      replication, so that eventually the loss of genetic material reaches a critical
      stage and the cells undergo senescence and cell death. A study was conducted to
      investigate the role of telomerase, an RNA-containing enzyme that restores the
      telomere length, in the neoplastic cell immortalization and progression process.
      Fresh human tissue samples taken from excision specimens received by the
      Department of Pathology, University of Malaya Medical Centre, were investigated
      for telomerase activity using a commercial Telomerase PCR-ELISA kit (Boehringer
      Mannheim). Specimens comprised 33 breast lesions (10 infiltrating breast
      adenocarcinoma, 13 fibroadenoma and 10 non-neoplastic breast tissue), 27 colonic
      lesions (17 colonic adenocarcinoma and 10 non-neoplastic colonic mucosa) and 42
      cervical lesions (20 cervical carcinoma and 22 non-neoplastic cervical tissues).
      Telomerase activity was found in 6 (60%) of 10 breast carcinomas, 6 (46%) of 13
      fibroadenomas, none of the 10 nonneoplastic breast samples, 3 (17.6%) of 17 colon
      carcinomas and none of the 10 non-neoplastic colonic mucosal samples, 12 (60%) of
      20 cervical carcinoma and 3 (13.6%) of 22 non-neoplastic cervical samples. 5/10
      (50%) Stage I, 4/7 (57%) Stage II, 2/2 (100%) Stage III and 1/1 (100%) Stage IV
      cervical carcinomas showed telomerase activity. These findings support a
      contributory role for telomerase in tumourigenesis with activation occurring from
      neoplastic transformation and increasing with tumour progression.

PMID- 19105327
TI  - Computer-linked image analysis of nuclear area: is there a use in diagnosis and
      grading of hepatocellular carcinoma?
AB  - Hepatocellular carcinoma (HCC) ranks as the fifth most common cancer with an
      increasing frequency worldwide. "Nuclear atypia", one of the critical features in
      histological diagnosis of malignancy and grading of the tumour, is generally
      ascertained through eyeballing. A study was conducted at the Department of
      Pathology, University of Malaya Medical Centre to assess whether nuclear area,
      (surrogate measure for nuclear size) and standard deviation (surrogate measure
      for nuclear pleomorphism) when objectively measured via computer-linked image
      analysis differs between (1) benign and malignant liver cells and (2) different
      grades of HCC. A 4-microm thick H&E stained section of 52 histologically re
      confirmed HCC with 36 having benign, non-dysplastic surrounding liver were
      analysed using the Leica Q550 CW system. 10 consecutive non-overlapping, non
      mitotic and non-apoptotic nuclei of HCC and surrounding benign hepatocytes
      respectively were manually traced at 400x magnification on the computer monitor
      and the nuclear area for the particular cell computed in arbitrary units by the
      Leica QWIN software. A total of 360 benign hepatocytic nuclei, 240 low grade HCC
      and 280 high grade HCC nuclei were traced. The mean nuclear area of the benign
      hepatocytes (37.3) was significantly smaller (p < 0.05) than that of both low
      grade (65.2) and high grade HCC (80.0). In addition, the mean nuclear area of
      high grade HCC was significantly larger (p < 0.05) than the low grade HCC. SD of
      the nuclear areas was lowest in benign hepatocytes (9.3), intermediate in low
      grade HCC (25.0) and highest in high grade HCC (25.6). These findings indicate
      that computer-linked nuclear measurement may be a useful adjunct in
      differentiating benign from malignant hepatocytes, in particular in small
      biopsies of well-differentiated tumours, and in predicting survival after
      surgical resection and transplant.

PMID- 19105328
TI  - Clinicopathological study of dentigerous cysts in Singapore and Malaysia.
AB  - This was a retrospective study of dentigerous cysts in people from the Singapore
      Malaysian region. The purpose of this study was to present the clinicopathologic
      features of dentigerous cysts in the Oriental population and to compare these
      data with those from other reported studies. Biopsy records from 1981 to 1993 of
      119 cases of dentigerous cysts from patients in Malaysia and Singapore showed
      that 36.1% of patients were female and 63.9% patients were male. Among patients
      with cysts, 70.5% were Chinese, 23.2% were Malays, 2.7% were Indian and 3.6% were
      other ethnic groups. The mean age of these patients was 30.2 +/- 17.3 years with
      a peak incidence occurring in the second and third decades. The location of the
      lesions was almost equal to the maxilla (50.9%) and the mandible (49.1%). There
      was a marked predilection for the posterior mandible (42.7%) followed by the
      anterior maxilla (38.2%). Histologically, 90.8% of the cysts were lined by a non
      keratinised stratified squamous epithelium. The cyst linings were mainly thin
      (90.0%) with 38.7% of cases having a mixed thick and thin lining. Mucous
      metaplasia was observed in 9 (7.6%) cases. Rushton bodies were seen in 3.4% of
      cases. Cholesterol clefts in the epithelial lining and lumen were found in 16.8%
      cases while 12.6% of cases exhibited cholesterol clefts in the cyst wall. Other
      cellular structures within the cyst wall were lymphocytes (66.4%), plasma cells
      (52.1%), Russell bodies (16.0%) and histiocytes (4.2%). Odontogenic keratocysts
      were observed in 5.0% of cases. One case of adenomatoid odontogenic tumour was
      also observed. Epithelial atypia was seen in 9.2% of cases, islands of stratified
      squamous epithelial cells in 8.4% of cases while one case showed a combination of
      these two features. In conclusion, some clinical features seen in this study are
      similar to that for the Caucasian population such as prevalence in male, peak
      incidence in the second and third decades and the predilection for the posterior
      mandible and anterior maxilla. Histopathologically, odontogenic keratocyst and
      adenomatoid odontogenic tumour were observed in dentigerous cysts.

PMID- 19105329
TI  - Cutaneous Rosai-Dorfman disease.
AB  - Rosai-Dorfman disease (RDD) is a rare benign proliferative disorder of
      histiocytes in the lymph nodes with or without extranodal involvement. RDD
      limited to the skin without nodal involvement, known as cutaneous Rosai-Dorfman
      disease, is very rare. We describe a 34-year-old female with RDD of the skin over
      the chest. A large nodule with satellite lesions was excised for
      histopathological examination. Microscopically, there were many large histiocytes
      (Rosai-Dorfman cells) exhibiting emperipolesis, among many plasma cells,
      lymphocytes and neutrophils throughout the dermis and the subcutaneous tissue.
      The histiocytes were immunohistochemically positive for S-100 protein but
      negative for CD 1a. Physical examination showed no lymphadenopathy or any extra
      cutaneous lesions. Serological tests indicated a past infection with Epstein-Barr
      virus and cytomegalovirus. The diagnosis of cutaneous RDD may be difficult in the
      absence of associated lymphadenopathy or any specific features of the skin
      lesion. Hence, not only is histopathological examination required for definitive
      diagnosis but a high index of suspicion by the clinicians and pathologists is
      essential to help diagnose this very rare disease.

PMID- 19105330
TI  - Gingival myofibroma in children: report of 4 cases with immunohistochemical
      findings.
AB  - Oral myofibroma is a rare tumour which usually occurs in children and has been
      reported in the mandible, tongue, buccal mucosa with only a few cases reported
      from the gingiva. It appears alarming clinically due to its fast growth which may
      mimic a malignancy. However, it is completely benign and is usually treated by
      complete surgical excision with excellent prognosis. Clinically, myofibroma
      presents as a single swelling when it occurs on the gingiva, and more common
      lesions such as fibrous epulis, pyogenic granuloma and peripheral odontogenic
      fibroma, myofibroma are usually considered in the differential diagnosis. We
      present 4 additional cases of gingival myofibroma in children. Their ages ranged
      from 7 to 14 years. Three were girls and 1 patient was a boy. All presented with
      solitary gingival growths, ranging from 3 weeks to 2 months in duration, and
      raised the clinical diagnoses of peripheral giant cell granuloma, pyogenic
      granuloma and fibrous epulis. Histopathology of incisional biopsies revealed
      proliferation of streaming and whorled fascicles of spindle cells around slit
      like vascular spaces. The spindle cells were cytologically bland and were
      immunopositive for vimentin and smooth muscle actin, but were negative for desmin
      and S-100 protein. All were treated by surgical excision.

PMID- 19105331
TI  - [Analyses of the expressions of GFAP in the brain tissues of hamsters infected
      with various amounts of scrapie strain 263K at terminal stage].
AB  - OBJECTIVE: To investigate whether gliosis in the brain tissues of the hamsters
      infected with various amounts of scrapie strain 263K is correlated with the
      inoculation doses or the incubation times. METHODS: The total values of glial
      fibrillary acidic protein (GFAP) in brains were evaluated by Western Blots and
      the GFAP-stained cells were detected by immunohistochemistry (IHC). The
      characteristics of GFAP distributions among various groups were defined by
      quantitive and statistic analyses. RESULTS: Compared with the brain tissues of
      normal hamsters, remarkably higher total GFAP levels and more GFAP-stained cells
      were observed in the brain tissues of infected ones, howbeit, no significant
      difference was addressed among the infected groups. CONCLUSION: Inoculations of
      various amounts of scrapie strain 263K into experimental hamsters intracerebrally
      induced the similar patterns of gliosis in the brains at the clinically terminal
      stage, regardless of infectious doses and incubation times.

PMID- 19105332
TI  - [Epstein-Barr virus infection and p16(INK4a) overexpression in gastric
      adenocarcinoma].
AB  - OBJECTIVE: To study Epstein-Barr virus infection and p16 protein abnormal
      expresson in carcinogenesis and progression of gastric adenocarcinomas (GAC).
      METHODS: Immunohistochemical staining SP method was used to detect the expression
      of LMP-1 and p16 in 97 cases of GAC. RESULTS: EBV LMP-1 and p16 protein were
      detected in 30.9% (30/97) and in 63.91% (62/97) cases of gastric adenocarcinomas
      respectively. There was no significant difference between EBV-positive and EBV
      negative gastric carcinomas in sex, histologic type, depth of tumor invision,
      lymph node metastasis and clinical stages (P > 0.05); overexpression of p16 was
      associated with lymph node metastasis and clinical stages; no correlation was
      found between the expression of EBV LMP-1 and p16 protein. CONCLUSION: 1. EBV
      play a role in carcinogensis of GAC. 2. P16 gene abnormality is frequently
      involved in GAC and might be one of the important prognostic factors. 3. EBV
      infection and p16 alteration are two independent roles in GAC carcinogenesis.

PMID- 19105333
TI  - [Construction of helper plasmids used in reverse genetic system of a cell adapted
      rabies virus strain].
AB  - OBJECTIVE: To construct four helper plasmids which are necessary in reverse
      genetic system of a cell adapted rabies virus strain. METHODS: Nucleoprotein
      gene, phosphprotein gene, glycoprotein gene and the viral RNA polymerse gene are
      amplified by RT-PCR. The four gene fragments were cloned into an expression
      vector respectively after sequencing to construct four helper plasmids. RESULTS:
      The four structral genus were amplified successfully, the sequence were correct.
      And all the structral protein gene fragments were cloned into expression vectors,
      the results were correct identified by cleavage reaction. CONCLUSION:
      Construction of the four helper plasmids have been done successfully, and it is
      the basis for rescuing the adapted cell rabies virus strain from cloned cDNA.

PMID- 19105334
TI  - [Detection of human papillomavirus in tissues of esophageal carcinomas by
      polymerase chain reaction].
AB  - OBJECTIVE: To investigate the relationship between the human papillomavirus (HPV)
      and esophageal carcinomas. METHODS: We detected HPV DNA in 31 fresh tissue of
      esophageal carcinomas from Linzhou City, Henan Province, by PCR with the general
      primer set of GP5+/6+ for HPV L1 gene and type-specific primer sets for HPV16 and
      18 as well. RESULTS: 29 from 31 esophageal carcinoma samples were HPV positive
      and the rate was 93.5%. Among the samples detected, 19 were HPV16E6 positive and
      rate was 61.3%, eight were HPV18 E6 positive and rate was 25.8%; our result also
      showed five were the multiple infection containing HPV16 and 18 as well and the
      rate was 71.0%. CONCLUSION: The high rate of HPV in the esophageal carcinoma
      samples suggested that HPV plays an etiologic role in the development of
      esophageal cancer in Linzhou City, Henan Province.

PMID- 19105335
TI  - [Dendritic cells transfected with recombinant adenovirus Ad5F35-LMP2 induces LMP2
      specific immunity mediated by cytotoxic T lymphocytes in vitro].
AB  - OBJECTIVE: To observe whether dendritic cells (DCs) transfected with recombinant
      adenovirus Ad5F35-LMP2 induces LMP2 specific immunity mediated by cytotoxic T
      lymphocytes in vitro. METHODS: Dendritic cells have been generated in vitro, and
      cocultured with autologous T cell after the DCs were infected with Ad5F35-LMP2,
      then the proliferation of the induced T cells and their cytotoxic activity
      against CNE-2 tumor cells which express EBV-LMP2 protein on membrane were
      assessed by MTT method. RESULTS: The dendritic cells could be transfected with
      Ad5F35-LMP2 and the CTL activated by Ad5F35-LMP2-DC could effectively suppress
      the proliferation of CNE-2 cells compared with control groups. CONCLUSION: The
      dendritic cells transfected with recombinant adenovirus Ad5F35-LMP2 showed
      cytotoxicity effect by activating T lymphocytes.

PMID- 19105336
TI  - [Genotypes of hepatitis B virus in Henan Luohe area].
AB  - OBJECTIVE: To determine the main genotype of hepatitis B virus (HBV) prevailed in
      Henan Luohe area. METHODS: Serum specimens were collected from 94 HBsAg positive
      individuals, and HBV S gene were obtained by PCR amplifying, and the gene
      sequences were analyzed and the polygenetic tree was drawn by the software MEGA3.
      RESULTS: About 75.7% samples of HBV S gene clustered in genotype C, about 20%
      samples clustered at genotype B in the HBV polygenetic tree, about 4.3% samples
      clustered at genotype D in the HBV polygenetic tree. CONCLUSION: The main
      genotype of hepatitis B virus prevalent in Henan Luohe is genotype C, genotype B
      is rarely seen, and genotype D is rarely seen.

PMID- 19105337
TI  - [Intracellular clearance of Coxsakievirus B3 infection by short interfering RNA
      and its mechanism study].
AB  - OBJECTIVE: To evaluate the possibility of short interfering RNA (siRNA)
      inhibiting Coxsackievirus B3 (CVB3) infection in vitro, and discover the
      mechanism initially. METHODS: We obtained proper effective dosage of siRNA by
      observing cytopathic effect (CPE). Estimate its antiviral activities and its
      pathway of siRNA by Western Blot assay and RT-PCR. RESULTS: Results showed that
      siRNA-3753 can be effectively transfected into HeLa cells, we can achieve a high
      transfection efficiency up to 98.77% and its effect can last for 48 h stably in
      cells. 0.6 micromol/L siRNA-3753 got a high inhibiting effect of virus and didn't
      show any toxicity to cells. So we consider this concentration as the experimental
      concentration. siRNA-3753 can debase virus reproduction. The antiviral effect is
      sequence-specific and is not attributable to either interferon or the interferon
      response effectors protein kinase R (PKR). CONCLUSION: The data confirmed that
      siRNA can effectively inhibit CVB3 infection in vitro, its antivirus effect was
      gained from specific debase of virus genome.

PMID- 19105338
TI  - [An investigation and analysis on an outbreak of acute gastroenteritis caused by
      genogroup I and II norovirus].
AB  - OBJECTIVE: To investigate the cause of an outbreak characterized by diarrhea and
      vomit in a middle school in Huzhou City. METHODS: Comprehensive analysis was
      conducted based on field epidemiological study, clinical characteristics of the
      cases and laboratory test. RESULTS: 578 cases of acute gastroenteritis were
      found. The attack rate was 23.58%. The most frequently observed clinical symptoms
      were diarrhea, vomiting, abdominal pain and nausea. Some few had fever. Most
      cases had slight clinical symptom with a course from 1 to 3 days. The cases were
      distributed in every class, showing no phenomenon of clustering. Norovirus were
      detected in 11 out of 15 stool samples by using RT-PCR. 6 were genogroup II
      norovirus. 3 were genogroup I norovirus. enogroup I and II norovirus were
      detected at the same time in 2 stool samples (the same student with 2 tests).
      Case-control study showed that drinking unheated bottled water was risk factor
      (OR = 2.46, 95% CI = 1.19-5.23), and had a dose response relation with the
      disease (chi = 24.8 P < 0.01). The epidemic was controlled soon through isolating
      patients during treatment, providing boiled water, disinfecting and health
      education. CONCLUSION: This was an infectious diarrhea outbreak caused by
      norovirus. The suspected transmission ways were drinking unheated bottled water
      and contact daily.

PMID- 19105339
TI  - [Analysis of influenza surveillance from 2000 to 2007 in Gansu province].
AB  - OBJECTIVE: To study the epidemical characteristics of influenza in Gansu province
      from 2000 to 2007, and to discuss the changes of the predominant strains of
      influenza virus. This study provide scientific basis for defending influenza
      effectively. METHODS: Influenza surveillance, collecting the pharyngeal swab
      specimens from influenza patients of national surveillance hospital and unsure
      influenza epidemic situations, inoculated on MDCK cell culture to obtain the
      influenza virus strains. RESULTS: 2001.10-2007.12, collecting the 6383 specimens,
      943 influenza virus strains were isolated, positive rate was 14.77%, 218 strains
      were A1 (H1N1 ), 352 strains were A3 (H3N2), 312 strains were B subtype of
      Victoria and 61 strains were B subtype of Yamagata. There were totally 61
      outbreak of influenza-like cases were observed in Gansu Province during the last
      5 years, 44 cases were isolated influenza virus, of 38 cases were caused by B
      subtype of Victoria virus strains, 3 cases were caused by H3N2, 2 cases were
      caused by B subtype of Yamagata virus strains, 1 cases were caused by H1N1.
      CONCLUSION: Influenza is active in human population. Influenza type A virus is
      predominant in winter and type B virus resulted in the outbreak in school and
      kidsgarden from March to June in the last 3 years.

PMID- 19105340
TI  - [Primary research of anti-influenza virus activity of "Benovoair Concentrate"].
AB  - OBJECTIVE: Anti-influenza virus activity of "Benovoair Concentrate". METHODS: The
      different dilution of samples were mixed with the same quantity of 100 TCID50
      virus at 37 degrees C for 30 minutes. Add suitable quantity mixture in wells
      containing cells. Every 3 wells were the same mode. Viruses control, cells
      control and samples control of different dilution were performed and set in the
      CO2 incubator at 37 degrees C. CPE was observed every day. When CPE appears in
      viruses control as "++++", stopped testing and performed the hemagglutination
      titration. RESULTS: "Benovoair Concentrate" with dilution of 1:60, 1:120, 1:240
      and 1:480 have 100% anti-influenza A and anti-influenza B activities. "Benovoair
      Concentrate" with dilution of 1:960 and 1:1920 have 25%-50% anti-influenza A and
      anti-influenza B activities. CONCLUSION: The test was the proof of anti-influenza
      virus activities which provided for the development of "Benovoair Concentrate".

PMID- 19105341
TI  - [The correlation between the polyomavirus DNA load and the dose of
      immunosuppressant].
AB  - OBJECTIVE: To explore the correlation between the polyomavirus DNA load and the
      dose of immunosuppressant in patients with allogene bone marrow transplantation
      (allo-BMT) for preventing the development of post-transplantational hemorrhagic
      cystitis. METHODS: Serial blood and urine samples from 122 cases of allo-BMT
      recipients were obtained and DNA was extracted from urine samples. Polyomavirus
      DNA-specific probe was synthesized and Fluorescence quantitative polymerase chain
      reaction was used for detecting the polyomavirus DNA loads and Fluorescence
      polarization immunoassay (FPIA) was performed for determining the dose of
      immunosuppressant Cyclosporin A (CsA) in blood. RESULTS: The altered polyomavirus
      DNA load in urine was followed by concentration of CsA in blood. When the
      concentration of CsA in blood was higher than 86-105 ng/ml, the positive rate of
      polyomavirus DNA load was significantly increased and both presented the linable
      correlation. CONCLUSION: In immunosuppression condition, polyomavirus DNA load
      correlated to the dose of immunosuppressant, which increased the risk of post
      transplantational hemorrhagic cystitis.

PMID- 19105342
TI  - [Effect of hepatitis B virus C protein on function of natural killer cell in NK
      92 cells].
AB  - OBJECTIVE: To investigate the influence of hepatitis B virus C protein on the
      function of natural killer cell. METHODS: Recombinant eukaryotic expression
      plasmid pHBI-CMV-HBC was constructed and confirmed by double restrictive enzyme
      digestion and DNA sequencing analysis. Then the recombinant plasmid was
      transfected into NK-92 cells with lipofectamine encapsuled. The transfected NK-92
      cells containing expressive HBV C protein was confirmed by Western Blot analysis.
      ELISA was employed to determine the IFN-gamma level secreted by NK-92 cells. And
      finally the cytotoxicities of NK cells were analysed by MTT colorimetry, with the
      hepatoblastoma cell line (HepG2) as target cell. RESULTS: Western blotting
      confirmed the expression of HBV C protein in the NK-92 cells transfected with
      pHBI-CMV-HBC. NK cytotoxicities and IFN-gamma secretion level of NK-92 cells
      transfected with recombinant plasmid significantly increased compared to control
      NK-92 cells transfected with blank plasmid (P < 0.01) and untransfected NK-92
      cells(P < 0.01). CONCLUSION: Transient expression of HBC can increase IFN-gamma
      secretion and cytotoxicities of NK-92 cells.

PMID- 19105343
TI  - [The immunostimulatory study on peripheral blood mononuclear cell and CD4+ T
      lymphocyte of HBV infections that were activated by CpG oligonucleotide].
AB  - OBJECTIVE: To study the effects of CpG oligodeoxyribonucleotide (ODN) as adjuvant
      on the immune responses in PBMC and CD4+ T cell with chronic hepatitis B virus.
      METHODS: The selected 20 infections were averagely divided two groups. The
      frequency of IFN-gamma secreting PBMC and CD4+ T cell in immune tolerant phase
      and in the immune clearance phase that had stimulated by CpG ODN, HBsAg and
      Mixture [CpG ODN + HBsAg] were analyzed by enzyme linked immune spot (ELISOT).
      RESULTS: The PBMC and CD4+ T cell were differently incubated by CpG ODN, HBsAg
      and M [CpG ODN + HBsAg]. The number of IFN-gamma spot differently are 3 +/- 8,
      339 +/- 429, 375 +/- 496, 1 +/- 4, 5 +/- 16 and 5 +/- 12; the results of immume
      tolerance are 3 +/- 8, 361 +/- 153, 375 +/- 276, 0 +/- 2, 2 +/- 2 and 4 +/- 4;
      but the results of immune clearance are 3 +/- 21, 289 +/- 345, 405 +/- 656, 2 +/-
      14, 8 +/- 40 and 7 +/- 30. The IFN-gamma spots statistical analysis of PBMC were
      differently incubated by HBsAg and M, the total is P = 0.720, The IFN-gamma spots
      statistical analysis of CD4+ T cell were differently incubated by HBsAg and M,
      the total is P = 0.890, The IFN-gamma spots statistical analysis of PBMC and CD4+
      T cell were differently incubated by M, the total is P = 0.000. CONCLUSIONS: The
      ability that CpG ODN can not significantly increase the IFN-gamma secreting of
      PBMC and CD4+ T cell that were incubated by HBsAg to the infection in immune
      tolerant phase and in the immune clearance phase, but the PBMC outweighed The CD4
      T cell.

PMID- 19105344
TI  - [Polymorphism analysis of human cytomegalovirus UL150 gene in low passage
      clinical isolates].
AB  - OBJECTIVE: To investigate the polymorphism of human cytomegalovirus UL150 gene in
      low passage clinical isolates and try to study the relationship between the
      polymorphism and different pathogenesis of congenital HCMV infection. METHODS:
      PCR was performed to amplify the entire HCMV UL150 gene region of 29 clinical
      isolates, which had been proven containing detectable HCMV-DNA by using FQ-PCR.
      PCR amplification products were sequenced directly and the data were analysed.
      RESULTS: 25 among 29 isolates were amplified and 18 isolates were sequenced
      successfully. By comparison with the sequence of Toledo and Merlin, the length of
      UL150 ORFs in all 18 clinical isolates was similar to that of Merlin than Toledo.
      CONCLUSION: HCMV UL150 DNA and deduced amino acid sequences is hypervariability.

PMID- 19105345
TI  - [Study on T cell subsets in HIV/AIDS patients].
AB  - OBJECTIVE: Analyze Naive and Mermory T cell subsets in HIV/AIDS patients and
      investigate their relationship with disease development. METHODS: T cell subsets
      from 15 normal control subjects, 79 HIV/ AIDS patients were detected by FCM.
      RESULTS: With diesase progression, CD4+ Naive cell counts and ratio was both
      decreased obviously (P < 0.001); CD4+ Tcm cell counts was significantly decreased
      (P < 0.001), CD4+ Tcm cell ratio was obviously higher (P = 0.002); CD4 TEM cell
      ratio was obviously increased( P < 0.001); CD8+ T Naive cell counts and ratio was
      also decreased obviously (P < 0.05); CD8+ T(CM), T(EM), T(EMRA) are not
      significantly different. CONCLUSIONS: The peripheral lymphocyte subsets in
      HIV/AIDS patients changed obviously. The counts of naive T cell decreased, while
      the proportion of memory T cell increased significantly. It will help to
      understand pathogenesis of HIV.

PMID- 19105346
TI  - [Expression and purification of TAT-HBX-EGFP fusion protein and its transmembrane
      distribution in mouse].
AB  - OBJECTIVE: To highly express TAT-HBX-EGFP fusion protein and study its
      distribution in mouse liver. METHODS: TAT-HBX-EGFP recombinant vector was
      constructed and fusion protein was induced by IPTG and expression in BL21; fusion
      protein was purified by Ni-NTA argarose, then injected into the peritoneal cavity
      of the mice. Distribution of fusion protein was observed by immunofluorescence.
      RESULTS: TAT-HBX-EGFP was highly expression in E. coli; HBX could be induced into
      mouse liver by TAT. CONCLUSION: HBX protein could be induced into mouse liver by
      TAT induced peptide.

PMID- 19105347
TI  - [Dynamic variation of HIV-1 CRF07_BC env gene in early HIV-1 infection].
AB  - OBJECTIVE: To understand the evolution of HIV-1 CRF07_BC envelope, we performed a
      longitudinal study on two patients during their early HIV-1 infection. METHODS:
      RNA was extracted from the plasma of the individuals and the C2-C5 fragments of
      the gp120 gene of HIV-1 were amplified by RT-PCR. Purified DNA segments were
      inserted into T easy vector and transformed into E. coli Top 10 competent cells.
      Positive clones were identified by blue-white screening, confirmed by PCR and
      sequenced by ABI 3700. RESULTS: The samples were collected from the patients
      every 6 months from seroconversion time. The genetic diversity and divergence in
      env gene showed consistent increases over time. Our sequence analysis also
      revealed obvious non-synonymous change in env C1, C3 and V4 regions among these
      samples. CONCLUSION: The results support the concept that the consistent pattern
      of viral evolution existed during early phase of HIV-1 infection. C1, C3 and V4
      region of env gene may be mainly immunological target during AIDS progression.

PMID- 19105348
TI  - [The measurement and significance of serum chemokine RANTES in patients with
      chronic hepatitis B].
AB  - OBJECTIVE: To investigate the relationship of the serum chemokine RANTES level in
      patients with chronic hepatitis B among different clinical severity and to
      explore its possible reasons. METHODS: 144 patients with chronic hepatitis B were
      divided into mild-moderate (46), serious (51) or severe group (47) according to
      the different clinical severity and 18 normal cases were taken as normal control.
      The serum level of chemokine RANTES was detected with an ABC-ELISA assay.
      Statistical analysis was performed on the software of SPSS 13.0. RESULTS: The
      serum chemokine RANTES levels in patients with chronic hepatitis B (2227.06 +/-
      790.80, 5878.49 +/- 3334.58, 3482.77 +/- 2315.62 ng/L in mild-moderate, serious
      and severe group respectively) were significantly higher than that in the normal
      control (329.46 +/- 152.00 ng/L). The differences between each two hepatitis
      groups were also statistically significant (P < 0.05) and serum chemokine RANTES
      level in serious group was highest among them. CONCLUSION: Serum chemokine RANTES
      level in patients with chronic hepatitis B elevates significantly and it might
      play an important role in the pathogenesis of chronic hepatitis B.

PMID- 19105349
TI  - [Expression of intrahepatic CD4+ CD25+ regulatory T cells in patients with
      chronic hepatitis B].
AB  - OBJECTIVE: To investigate the expression and distribution of intrahepatic CD4+
      CD25+ regulatory T cells in immuno-tolerant and immuno-clearance phase of
      patients with chronic hepatitis B. METHODS: The expression of FoxP3 was detected
      in 19 cases of immuno-tolerant phase and 12 cases of immuno-clearance phase by
      immunohistochemistry. The relation between the intrahepatic expression of FoxP3
      and the clinicopathological features were analyzed. RESULTS: The positive signal
      of FoxP3 is located in nuclear of lymphocyte and mainly aggregated in portal
      areas as well as occasionally scattered in hepatic sinusoids. The expression of
      intrahepatic FoxP3 in the group of immuno-tolerant phase was significantly
      increased than those in normal control (P < 0.01), and greatly decreased than
      those in immuno-clearance phase (P < 0.01). No correlation was observed among the
      expression of intrahepatic FoxP3, ALT, levels of HBV DNA, HBeAg positive, in
      patients of immuno-clearance phase, respectively. There were significant
      differences between immuno-tolerant phase and immuno-clearance phase age, ALT,
      TBIL, PTA, HBV-DNA and detection of HBeAg but not in sex and family history of
      HBV infection. CONCLUSION: CD4+ CD25+ regulatory T cells may play important roles
      in the clearance of HBV as well as in liver inflammation and injury during
      chronic HBV infection.

PMID- 19105350
TI  - [Significance of human papillomavirus test in triage of patients with atypical
      squamous cell of undetermined significance].
AB  - OBJECTIVE: To investigate the significance of human papillomavirus test in triage
      of patients with atypical squamous cell of undetermined significance (ASCUS)
      diagnosed by cervical cytology. METHODS: Human papillomavirus test,colposcope and
      cervical biopsy were performed in 184 patients with a referral diagnosis of ASCUS
      by cervical cytology. RESULTS: Confirmed by pathological diagnosis of cervical
      biopsy, 112 cases were chronic inflammation (60.87%), 33 CIN I (17.93%), 17 CIN
      II (9.24%), 8 CIN III (4.35%), 4 cervical squamous carcinoma (2.17%) and 10
      condyloma (5.43%). Of the 184 women with cytological ASCUS, 124 (67.39%) cases
      were positive in high-risk HPV test among which 66 cases were histologically
      confirmed as chronic inflammation (53.23%), 22 as CIN I (17.74%), 16 as CIN II
      (12.90%), 8 as CIN III (6.45%), 4 as cervical squamous carcinoma (3.23%) and 8 as
      condyloma (6.45%). The positive rate of HPV in groups of ASCUS were higher than
      those with negative HPV (P < 0.003). CONCLUSION: Women with ASCUS should be
      tested for HPV. Cervical biopsy under colposcopy is recommended for women with HR
      HPV infection.

PMID- 19105351
TI  - [Verruca planae Chinese medicine treatment].
AB  - OBJECTIVE: Flat wart on the effectiveness of TCM treatment. METHODS: Outpatients
      will be by the "People's Republic of China Chinese medicine industry standards,
      TCM diagnosis of dermatological diseases efficacy standards, Chen Hou State
      Administration of Traditional Chinese Medicine 1994-06-28 approved, 1995-01-01
      implementation". Randomly divided into two groups. Treatment and control groups.
      Treatment groups treated with Chinese herbs. The control group were treated with
      WM. Since the preparation of the unification formula ointment, cuboiling method.
      Chinese herbal medicine preparation by my hospital room Producer. 5 g pre pack,
      after treatment for 30 days, clinical observation. RESULTS: The group of Chinese
      medicine is better than western medicine (86.7% vs 71.7% , P < 0.05). CONCLUSION:
      Chinese medicine has some effect flat wart.

PMID- 19105352
TI  - [Development of an extraction and concentration method for the detection of
      hepatitis A virus in different samples].
AB  - OBJECTIVE: To develop an extraction and concentration method for the detection of
      hepatitis A virus (HAV) in shellfish, water, serum and saliva samples by nested
      RT-PCR. METHODS: HAV were artificially inoculated into the above samples, calm
      sample was extracted using glycine buffer pH9.5, PEG precipitation; water sample
      was PEG precipitated directly; then all the samples including serum and saliva
      samples were extracted using Trizol regent, followed by nested RT-PCR detection
      using primers from HAV VP1-2A region. RESULTS: The detection limit for HAV in
      cultured cell lysis was 0.1TCID50; in water, serum or salva sample was 1TCID50
      respectively, in calm sample was 1-10 TCID50. HAV RNA was detected in water and
      sera samples collected from the HAV outbreak region, sequenced and analysis.
      CONCLUSION: The method developed here is convenient, specific and capable of
      detecting low levels of HAV in different samples, would be useful for diagnostic
      laboratories in order to perform HAV analysis in cases of foodborne infections or
      for molecular epidemiology investigation of HAV outbreaks.

PMID- 19105353
TI  - [Overexpression, purification of recombinant HIV-1 gp41 protein and detection of
      HIV antibody in urine].
AB  - OBJECTIVE: To establish a specific and sensitive Enzyme-linked immunosorbent
      Assay (ELISA) kit for detection of HIV-1 antibody in urine using Escherichia coli
      expression products as coating antigen. METHODS: The truncated HIV-1 gp41 gene
      fragment of major antigenic epitopes was inserted into the plasmid pET22b to
      obtain expression plasmid pET22b-mgp41. The recombinant antigen was expressed in
      BL21 (DE3) strains of Escherichia coli and was purified by immobilized metal
      chelation and gel filtration chromatography. Using this antigen as coating
      antigen, a HIV-1 urine antibody ELISA kit was developed. In order to examine the
      clinical utility of the kit, 5437 urine samples were assayed, which consisted of
      641 urine samples from HIV infected patients and 4796 samples from normal
      subjects. Results The purity of purified antigen is up to 95%. Anti-HIV
      antibodies were detected in all the urine samples from HIV infected patients, and
      the diagnostic sensitivity for HIV-1 infection was 100%. In healthy control
      group, 71 cases showed false positive, the specificity was 98.52%. CONCLUSION:
      The HIV-1 urine antibody kit can be used in screening and diagnosing for HIV-1
      infection.

PMID- 19105355
TI  - [The importance of site rescue and late treatment of spine injury and spinal cord
      injury in earthquake].

PMID- 19105354
TI  - [Preparation of the national reference panel for hepatitis B surface antigen].
AB  - OBJECTIVE: To establish the national quantity standard of hepatitis B surface
      antigen according to the world health organization' s standard material and
      prepare the national liner reference panel for hepatitis B surface antigen.
      METHODS: Sera from hepatitis B patients and health blood donors in different
      areas were collected and detected by domastic HBsAg kits, anti-HBs kits, HBeAg
      kits, anti-HBe kits, anti-HBc kits and anti-HCV, and then confirmed by the kits
      produced by Abbott, which was approved by WHO. One serum with high concentration
      of HBsAg was calibrated with the standard sample of WHO. And then it was diluted
      by 1.5 fold as the liner HBsAg reference panel. RESULTS: The HBsAg concentration
      of one serum was 1226 IU/ml calibrated by 21 independent standardization
      measurements with 7 kinds of kits. The coefficient of variation of each
      calibration were less then 15%. A panel contained 8 serial dilutions was
      established as the national liner HBsAg reference panel. The permitted range of
      every dilution was stipulated and the stability of the panel was detected by
      accelerated test. CONCLUSIONS: The national quantity standard of hepatitis B
      surface antigen was established and the national quantitative reference panel for
      HBsAg which contains eight liner serum was developed.

PMID- 19105356
TI  - [First aid of casualties in Wenchuan earthquake].

PMID- 19105357
TI  - [The comparative study of patients with severe polytrauma treated by damage
      control orthopedits in normal time and in earthquake].
AB  - OBJECTIVE: To compare the outcome of damage control in patients with severe
      polytrauma in normal time and in the earthquake of 2008 Sichuan China. METHODS:
      In the retrospective study, 26 cases with severity polytrauma in peacetime and 24
      cases with severe polytrauma who have mainly sustained in the earthquake of 2008
      Sichuan China were involovd. The patients' demographics, the methods and effects
      of damage control were evaluated. RESULTS: In the earthquake group, 24 cases
      succeeded in the rescuing life; among whom, 3 patients needed the further
      debridement and dermoplasty. In the normal time group, 26 cases succeeded in the
      rescuing life; among whom, 19 patients had returned to their former work and 3
      patients needed the further treatment. There was no difference between two groups
      in therapeutic effects (P > 0.05). CONCLUSION: Both in earthquake and in normal
      time, treating the severity polytrauma by damage control orthopedics can acquire
      satisfied effect.

PMID- 19105358
TI  - [Characteristics of traumatic condition and main points of remedy of casualties
      transmitted from wenchuan earthquake area].

PMID- 19105359
TI  - [Definitive postponed surgery for the casualties with multiple injuries in the
      earthquake].
AB  - OBJECTIVE: To explore the treatment of casualties who suffered from multiple
      injuries in earthquake and had been treated by damage control (DC)
      immediately,and the definite postponed surgery time by way of APACHE II score.
      METHODS: From May to June 2008, 21 casualties who had undergone DC accepted
      further treatment of medicine and surgery, and recovered physical potentiality in
      the intensive care unit (ICU). APACHE II score was adopted to evaluate the
      casualties' physical potentiality. Then, internal fixation of intra-articular
      fractures and centrum fractures, alternation from external fixation to internal
      fixation, reconstruction of soft tissue was applied by stages according to the
      plan. RESULTS: All the patients were effectively cured after definite postponed
      surgery. There was less complication, low deformity ratio and no death happened.
      CONCLUSION: Timely evaluation of the casualties' physical potentiality,
      appropriate surgery time and exact surgery can reduce the casualties'
      complication, deformity rate and death rate.

PMID- 19105360
TI  - [Imaging diagnosis of the vertebral injury in earthquake].
AB  - OBJECTIVE: To explore the clinical value of imaging diagnosis of the vertebral
      injury in earthquake. METHODS: Twenty-two cases of the vertebral injury in
      earthquake with clinical and imaging data were analyzed retrospectively. All of
      the cases were performed X-ray plain film examination, CT in 20 cases and MRI in
      15 cases. RESULTS: Imaging examination can establish definitive diagnosis in all
      cases. In the 22 cases, the vertebral compression fracture was found in 20 cases,
      and vertebral bursting fracture in 2 cases,single-level vertebral fracture in 12
      case,and multiple-level vertebral fracture in 10 case. Among the 31 vertebral
      bodies of fracture, the fracture of cervical vertebra, thoracic vertebra, lumbar
      vertebra and sacral vertebra was found in 3, 12, 14, 2 vertebral bodies,
      respectively. CONCLUSION: Imaging examination is the most valuable examination
      method in diagnosis of the vertebral injury in earthquake. It can not only make
      definitive diagnosis, but also play an important role in selection of therapeutic
      method.

PMID- 19105361
TI  - [Treatment of the aged wounded patients evacuated from Wenchuan earthquake area].
AB  - OBJECTIVE: To explore the therapeutic strategies of the aged wounded patients
      evacuated from Wenchuan earthquake area. METHODS: The characteristics of
      traumatic conditions and therapeutic methods of 14 aged wounded patients
      evacuated from Wenchuan earthquake area were retrospectively analyzed. RESULTS:
      All cases accepted the effective treatment for 4 to 8 weeks and attained good
      recovery. There was no anesthetic and surgical complications, deep venous
      thrombosis, hypostatic pneumonia, pulmonary embolism, bed sore, stroke and other
      complications happened. When discharged, all medical disorders of the patients
      were under control and both psychological condition and nutritional status were
      improved obviously. CONCLUSION: Assessment of traumatic condition and general
      status,cooperative nursing, active nutritional support, positive symptomatic
      treatment and necessary psychological intervention are the key to improve
      effectively the curative effect of the aged wounded patients in earthquake.

PMID- 19105362
TI  - [Analysis of traumatic conditions on casualties evacuated from Wenchuan
      earthquake area].
AB  - OBJECTIVE: To investigate and analyze the traumatic conditions on the casualties
      evacuated from Wenchuan earthquake area. METHODS: Traumatic conditions of 34
      patients evacuated to Changhai hospital were investigated. Meanwhile,
      classification of traumatic conditions and therapeutic methods was analyzed.
      RESULTS: By organized emergency medical treatment,classification and transmission
      of casualties, selected application of external fixation,active repair of soft
      tissue injury, positive psychological assessment and intervention, healing rate
      was efficiently rasied and complications were decreased. CONCLUSION: The summary
      of traumatic conditions and therapeutic experiences on wounded people of Wenchuan
      earthquake area can provide the primary basis and treatment methods for the
      wounded people with earthquake injury.

PMID- 19105363
TI  - [Diagnosis and treatment of peripheral nerve injury in Wenchuan earthquake: a
      report of 14 cases].
AB  - OBJECTIVE: To discuss the diagnosis and treatment of peripheral nerve injury in
      the earthquake. METHODS: Fourteen patients with peripheral nerve injury injured
      in the earthquake were involved the retrospective study. All cases accepted the
      timely diagnosis and treatment including anastomosis and repair of the nerve and
      other conservative treatments. Then the therapeutic effects were observed.
      RESULTS: All 14 patients got short-term follow-up and attained the improvement in
      their symptoms of nerve injury. CONCLUSION: Peripheral nerve injury has a high
      incidence in the earthquake. Prevention is very important. The timely and
      effective treatment should be taken according to spot situations and traumatic
      conditions of casualties in earthquake.

PMID- 19105364
TI  - [Characteristics and therapeutic experiences of leg open fractures in earthquake
      casualties].

PMID- 19105365
TI  - [Analysis of fracture conditions and therapeutic experiences of earthquake
      casualties].
AB  - OBJECTIVE: To analyze the fracture conditions of earthquake casualties, summarize
      the therapeutic experiences and explore the frontier treatment model. METHODS:
      The clinical data of spot treatment of fracture patients in Wenchun earthquake
      were collected and analyzed to observe the therapeutic effects of operative
      patients and to verify the rationality of the cooperated remedy model of unified
      military and civilian hospitals. RESULTS: Among 236 fracture patients admitted in
      hospital, there were patients with extremities fractures in 81.3%, multiple
      fractures in 11.4% and open fractures in 10.6%. In all 55 patients underwent
      surgical treatment,the functional improvement rate was 65.5% and no infection or
      amputation happened. Supported by psychological aids, all patients were
      coordinated with treatment and the short-term outcome was parallel with that of
      ordinary fracture cases. CONCLUSION: The general conditions of patients should be
      paid more attention to during the treatment procedure of fractures because of the
      great quantity of casualties and severe traumatic conditions in Wenchun
      earthquake. The cooperated remedy model of unified military and civilian
      hospitals should be regarded as a new sanitation service practice with certain
      advantages. Psychological aids can provide strong support for the patients'
      postoperative rehabilitation.

PMID- 19105366
TI  - [Investigations and analysis of traumatic condition of Longnan area in Wenchuan
      earthquake].
AB  - OBJECTIVE: To investigate and analyze the traumatic conditions of Longnan area of
      Gansu in Wenchuan earthquake, and to explore the measures coping with unexpected
      disasters. METHODS: A sample survey including questionnaire survey, interviews
      and other methods was adopted to investigate the conditions of affected
      population of Longnan area in earthquake, especially on the traumatic conditions,
      the injured causes, treatment methods. RESULTS: In the sample survey of a total
      of 1652 earthquake casualties, the dead were 16 and the patients with extremities
      fractures were 750 (45.4%). Organized and timely rescue of the wounded could
      reduce the complications and the mortality . CONCLUSION: Strengthening the
      prevention and treatment of earthquake trauma can effectively decrease the death
      rate and disabled rate.

PMID- 19105367
TI  - [Clinical observation on the influence of earthquake crush injury on
      postoperative wound healing of extremity fractures].
AB  - OBJECTIVE: To observe the influence of earthquake crush injury on postoperative
      wound healing of extremity fractures. METHODS: The study involved 85 patients
      with extremities fracture underwent internal fixation operation in 3 group,
      including 28 earthquake casualties with crush injuries in observation group, 27
      earthquake casualties without crush injuries in control I group and 30 local
      patients during the same period in control II group. Urine routine, blood
      creatine kinase (CK) and wound conditions of patients in 3 groups were observed
      respectively. RESULTS: There was no significant difference in Urine routine and
      blood CK between 3 groups and was significant difference in wound conditions
      between observation group and each control group. CONCLUSION: Earthquake crush
      injuries can influence the postoperative wound healing of extremity fractures.

PMID- 19105368
TI  - [Treatment of severe crush syndrome caused by earthquake: a report of 35 cases].
AB  - OBJECTIVE: To discuss the diagnosis and treatment of the crush syndrome in the
      earthquake. METHODS: Thirty-five patients with crush syndrome caused by
      earthquake were involved the retrospective study. The role of nutritional
      support, active wound treatment and hemodialysis on the patients' recovery was
      observed. RESULTS: The function of the heart and kidneys were gradually improved
      by the planned removal of the necrotic tissue, which laid a foundation for the
      further repair of the wound. CONCLUSION: The removal of necrotic tissue, which
      can decrease the toxic absorption, will improve the success rate for treatment of
      the crush syndrome patients when being assisted with the hemodialysis.

PMID- 19105369
TI  - [Treatment of casualties transmitted from earthquake area: a report of 15 cases].

PMID- 19105370
TI  - [Design and experimental study of an epiphyseal slide-traction plate].
AB  - OBJECTIVE: To develop an epiphyseal slide-traction plate in child, which can
      supply the fracture a sufficient internal fixation, and will not restrain the
      growth of epiphyses. Animal experiments were carried out with the plates to
      compare the slide-traction with traditional plate. METHODS: Develop a slide
      traction plate for the configuration of the femur condylus of children. Thirty
      adolescent goats in the experiment were divided into control group (12 goats) and
      plate group (18 goats). In plate group, right femurs of goats were fixed with
      common plates and the left femurs with slide-traction plates. All the goats were
      given X-ray examination at different time after surgery. And the goats were
      sacrificed at 3 and 6 month, histological method and electron microscopy were
      performed to evaluate the development of epiphyseal plate. RESULTS: The both
      femurs of the goats in control group have no difference in evidence in length at
      all time we examined. And the both femurs of the goats fixed with plates have no
      difference in evidence in length at 1 day after surgery. However, the both femurs
      of the goats fixed with plates have difference in evidence in length at 1 month,
      2 month, 3 month, 6 month after surgery. The increased length of the femurs at I
      month, 2 month, 3 month, 6 month after surgery was also compared with the length
      at 1 day after surgery, there was difference in evidence between the right femurs
      of the control group and the femurs were fixed with common plates, but no
      difference in evidence between the left femurs of the normal control group and
      the femurs were fixed with slide-traction plate (P > 0.05). More thicker
      epiphyseal plate were found in the left femurs than the right femurs of the group
      fixed with plates at 3 and 6 month after surgery (P < 0.01). In the plate group,
      safranine O staining showed epiphyseal plates at the left femurs had more fuscous
      staining than the right femurs at 3 and 6 month after surgery and electron
      microscopy also found that the cells of the epiphyseal plates of left femurs were
      more eugenic than the right femurs at 3 and 6 month after surgery. CONCLUSION:
      The epiphyseal slide-traction plate can slide with the growth of epiphyses, which
      is suitable for fixation of the fracture in this part.

PMID- 19105371
TI  - [Repair of the soft tissue defects of the anterior foot and the ankle with the
      reversed sural neurocutaneous flap].
AB  - OBJECTIVE: To investigate the operative method and effect of the reversed sural
      neurocutaneous flap in repairing soft tissue defects of the anterior foot and the
      ankle. METHODS: From March 1999 to November 2004, 19 cases (17 male, 2 female) of
      soft tissue defects of the anterior foot and the ankle were repaired with the
      reversed sural neurocutaneous flaps. The flap sizes range from 18 cm x 9 cm to 30
      cm x 18 cm. RESULTS: All flaps survived well, while 1 flap had distal partial
      necrosis and healed after dressing change. The follow-up from 6 months to 2 years
      showed that all flaps were satisfactory. CONCLUSION: Sural neurocutaneous flap is
      easy to get and to survive. It is an effective method to repair the soft tissue
      defects of the anterior foot and the ankle.

PMID- 19105372
TI  - [The comparative study of effect of a modified open door laminoplasty using
      anchor method on axial symptoms and cervical curvature].
AB  - OBJECTIVE: To evaluate the effect of a modified open door laminoplasty using
      anchor method on reducing the occurrence of axial symptoms and loss of cervical
      curvature. METHODS: From October 2004 to May 2007,56 patients with cervical
      spondylotic myelopathy underwent this procedure and been followed up (group A).
      Another 50 patients who underwent conventional unilaterally open-door
      laminoplasty served as control (group B). The operation time, blood loss, JOA
      scores and the incidence of newly developed or deteriorated axial symptoms were
      recorded. Preoperative and postoperative curvature angle which was presented on
      the tangent of posterior vertebral body margins of C2 and C7 in the cervical
      spine were measured on cervical radiographs. RESULTS: The operative time was (116
      +/- 27.9) min in group A and (120 +/- 18.9) min in group B,showing no
      statistically significant difference (P > 0.05). The operative blood loss was
      (148 +/- 68.3) ml in group A and (152 +/- 63.4) ml in group B (P > 0.05).
      According to JOA scores, the average recovery rates were (61.1 +/- 24.5)% in
      group A and(53.3 +/- 23.3)% in group B (P < 0.05). Postoperative development or
      deterioration of axial symptoms occurred in 41.1% of patients in group A and
      76.0% of patients in group B,showing statistically significant difference (P <
      0.05). There was no significant difference between preoperative (6.3 degrees +/-
      5.1 degrees) and postoperative (6.6 degrees +/-4.5 degrees) cervical curvature
      angle in group A,whereas the mean value of postoperative angle(4.8 degrees +/-
      3.5 degrees) was significantly smaller than that of preoperative one(5.9 degrees
      +/- 5.1 degrees) in group B (P < 0.05). CONCLUSION: The modified open door
      laminoplasty using anchor method was effective on reducing the occurrence of
      axial symptoms and loss of cervical curvature and to the benefit of early
      functional training.

PMID- 19105373
TI  - [An imaging study on location of the anterior border of facets and the posterior
      border of vertebral bodies in lower cervical spine].
AB  - OBJECTIVE: To explore the location of the anterior border of facets and the
      posterior border of vertebral bodies in lower cervical spine,and to provide a
      quantitative data to evaluate the correct length of transarticual screws in lower
      cervical spine during procedure. METHODS: One hundred standard lateral X-ray
      films and fifty CT films on cervical spine were used to measure the distance of
      the anterior border of facets and the posterior border of vertebral bodies in
      lower cervical spine. HS, HM and HI were defined as parameters, which means the
      distance between the anterior border of the superior (HS), median (HM) and
      inferior (HI) part of facets and the posterior border of corresponding vertebral
      bodies. The value will be negative if the anterior border of the facet located
      before the vertebral body. RESULTS: 'HS > HM > HI' was found in all facets in
      lower cervical spine. The anterior border of the facet in C(3,4) located before
      the posterior border of the vertebral body of C3. The anterior border of C(4,5)
      and C(5,6) was inclined to posterior. The anterior border of C(6,7) located after
      the posterior border of the vertebral body of C6. The pattern of HS increased
      from C(3,4) to C(6,7), the minimal (0 +/- 0.25) mm and the maximal (2.91 +/-
      1.05) mm. The tendency of HM raised from C(3,4) to C(6,7), the minimal (-1.57 +/-
      0.53) mm and the maximal (1.54 +/- 0.39) mm. The pattern HI added from C(3,4) to
      C(6,7), the minimal (-2.03 +/- 0.40) mm and the maximal (1.08 +/- 0.70) mm.
      CONCLUSION: During the implantation of the transarticular screws, the tip of the
      screws should be 0-2 mm before the posterior border of the vertebral body of C3
      at C(3,4), 0-2 mm after that of C4 at C(4,5), 0.5-2.5 mm at C(5,6) and 1-3 mm at
      C(6,7). The quantitative location between the anterior border of facets and the
      posterior border of the corresponding vertebral bodies can offer an indirect
      method to evaluate the correct length of transarticual screws in lower cervical
      spine during procedure.

PMID- 19105374
TI  - [The comparisive study of the clinical effect of rotary self-locking
      intramedullary nail and intramedullary interlocking nail for the treatment of
      femur fracture].
AB  - OBJECTIVE: To compare the clinical effect of rotary self-locking intramedullary
      nail (RSIN) and intramedullary interlocking nail (IIN) for the treatment of fresh
      femoral shaft fracture. METHODS: The radiological records of 60 fresh femoral
      shaft fractures (41 stable fractures and 19 unstable fractures) were
      retrospectively analyzed. Among them, 49 were male and 11 were female. The
      average age was 33.5 years old (range from 12 to 68 years old). All cases were
      fresh fracture with no important blood vessel or nerve injury, which were taken
      operation with RSIN on IIN respectively in 2 h-7 d after injury. The patients in
      IIN group began functional movements at postoperative 4 to 5 days and could bear
      the weight of 10-15 kg. The patients in RSIN group could began functional
      exercises after the wound healed and bear partly weight after 6 weeks. Both
      groups were contrasted on the biomechanics, operation procedure, fracture healing
      time, functional recovery and operative indication. RESULTS: Both groups were
      followed-up for average 13 months. IIN group: the average healing time of closed
      femur fracture was 16 weeks while that of open fracture was 20 weeks. The healing
      rate was 100% and the malunion rate was 7.9%. The excellent and good rate of
      functional recovery was 93.3% including excellent in 27 cases, good in 1, fair in
      1 and bad in 1. RSIN group: the average healing time of closed femur fracture was
      16 weeks while open fracture was 23 weeks. The healing rate was 87% and the
      malunion rate was 18.2%. The excellent and good rate of functional recovery was
      83.3% including excellent in 23 cases, good in 2, fair in 3 and bad in 2. No
      implant break and nonunion happened. The differences between two groups in
      healing time, deformity-union rate and the rate of the twice operation were
      statistically significant. CONCLUSION: IIN provides a reliable and practical
      alternative method for the treatment of all kinds of femoral shaft fracture and
      its important complication is fewer than RSIN group. RSIN also has a good
      curative effect in its own indication.

PMID- 19105375
TI  - [Analysis on misdiagnosis of ulnar nerve injury: a report of 18 cases].

PMID- 19105376
TI  - [Biomechanical study of new type two-head automatic pressure external fixator
      (TAPEF) for the treatment of intertrochanteric fracture].
AB  - OBJECTIVE: To investigate the mechanical characteristics of new type two-head
      automatic pressure external fixator in the view of biomechanics. METHODS: Fifteen
      fresh and humid specimens were selected and divided into experimental group (5
      cases) and control group (10 cases). The control group were respectively applied
      with DHS (5 cases) and traditional external fixator (5 cases). In order to
      compare the different apparatus, the strength, stiffness and twist mechanical
      function of femoral intertrochanteric fracture with different device were
      measured respectively when the specimens were under the pressure of 0-1800 N and
      loading speed 1.4 mn/min. RESULTS: The strength, stiffness, twist mechanical
      function and maximum endurance of femora in the experimental group were obviously
      superior than that of DHS and traditional external fixator (P < 0.05).
      CONCLUSION: Two head automatic new type pressure external fixator can embed more
      tightly without sliding, also can prevent the occurrence of coxa vara
      effectively.

PMID- 19105377
TI  - [Effect of zhenggu powder ([Chinese characters: see text]) on the inflammatory
      cell factor of soft tissue in experimental acute injury].
AB  - OBJECTIVE: To probe the recovery mechanism of Zhenggu powder (ZGP) on acute soft
      tissue injury in cell levels. METHODS: Forty rabbits which established animal
      model of acute soft tissue injury with hammer hitting,were divided randomly into
      normal group (A), model group (B), vaseline group (C)and ZGP group (D). Injured
      part was applied external drug daily after model was made. All animals were
      killed after using drug for 4 days. The local tissue of injured part was taken
      pathologic study, and was measured the content of IL-1beta, IL-6, TNFalpha by
      ELISA method and TXB2, 6-keto-PGF1alpha by RIA method. RESULTS: Muscular tissue
      of group A was normal. But that of group B and C was aberrant,such as swelling
      and broken of muscular fiber or infiltration of inflammatory cell. Such
      histological change of group D was lightly and hyperplasia of blood vessel was
      found. The contents of IL-1beta, TNFalpha, TXB2 and TXB2/6-keto-PGF1alpha in
      group D were lower than that of group B and group C. On the contrary, the
      contents of 6-keto-PGF1alpha in the group D were higher than that of group B and
      group C. The difference of content of IL-6 between groups was not obvious.
      CONCLUSION: ZGP could promote not only the dilution and the transportation of
      inflammatory cell factors,but also the repair and the regeneration of the injured
      tissue structures. The therapeutic effect of ZGP was not relative to IL-6.

PMID- 19105378
TI  - [Three-tunnels core decompression with implantation of bone marrow stromal cells
      (bMSCs) and decalcified bone matrix (DBM) for the treatment of early femoral head
      necrosis].
AB  - OBJECTIVE: To analyse retrospectively 3-tunnels core decompression with
      implantation of bone marrow stromal cells(bMSCs) and decalcified bone matrix
      (DBM) for treatment of femoral head necrosis in early stages, and to study its
      therapeutic results and indications. METHODS: According to the University of
      Pennsyvania system of classification and staging,to treat the patients with 3
      tunnels core decompression with implantation of bone marrow stromal cells (bMSCs)
      and decalcified bone matrix (DBM) for treatment of early femoral head necrosis.
      Among the total 87 patients (103 hips), the male was 71 (86 hips) and the female
      16 (17 hips) with the average age of 47 years old. The average course of disease
      was 1.3 year. The effect was evaluated by the clinical symptoms, the Harris'
      scores and the manifestations of radiology before and after operation. RESULTS:
      All the patients were followed up more than 2 years (average 26 months). The
      average Harris' scores increased from preoperation 47.3 to postoperation 74.0.
      The average rate of excellent and good results was 75.7%. The rate of excellent
      and good was 88% (22/25) in type I, 78.7% (37/47) in type II and 61.3% (19/31) in
      type III. No severe complications were observed. CONCLUSION: Three-tunnels core
      decompression with implantation of bMSCs and DBM not only removal the focus of
      disease, but also use DBM the induction of bone and autologous hone marrow stem
      cells to differentiate the functions of the femoral head can be resumed loading
      structure, eliminate pain,improve joint function. It is an effective method for
      early femoral head necrosis.

PMID- 19105379
TI  - [The value and strategy of the treatment for fractures of tibia and fibula by
      steel plate in Tibet].

PMID- 19105380
TI  - [Prevention of ulnar nerve injury during fixation of supracondylar fractures in
      children by a medial-lateral three-pin fixation technique].
AB  - OBJECTIVE: To expore the prevention of ulnar nerve injury during fixation of
      supracondylar fracture in children by a medial-lateral three-pin fixation
      technique. METHODS: Eighty-one patients including 54 boys and 27 girls with
      average age of 6 years old (2.5 to 11 years)were treated by a three-pin fixation
      technique with insertion of two Kirscher wires from the lateral side and the
      third wire through the medial side. They were followed-up without any
      complications related to the ulnar nerve. According to Garland system, there were
      25 cases of type II supracondylar fracture and 56 of type III. All patients were
      treated by a medial-lateral three-pin fixation technique, and external fixation
      with plaster for 3 weeks. RESULTS: All cases achieved immediate stability and
      long-term bony fusion postoperatively and no iatrogenic ulnar nerve injury
      happen. CONCLUSION: The technique is a stable and reliable methods for unstable
      supracondylar fracture and the iatrogenic injury ulnar nerve can be avoided
      completely.

PMID- 19105381
TI  - [Manipulative reduction for the treatment of subluxation of radial head: a report
      of 93 cases].

PMID- 19105382
TI  - [Anterior cruciate ligament reconstruction with hamstring tendons preserved
      tibial insertion and an implant fixation technique of hamstring tendon knot and
      bone bolt press-fit].
AB  - OBJECTIVE: To evaluate the feasibility of hamstring autograft anterior cruciate
      ligament reconstruction with hamstring tendons insertion on tibia preserved and
      an implant fixation technique of hamstring tendons knot and bone bolt press-fit.
      METHODS: Twenty cases of injured anterior cruciate ligament were reconstructed.
      There were 15 males and 5 females with the average age of 22 years old. Ten left
      knees and 10 right knees were involved. Hamstring tendons were taken, and
      pretension was performed. Tibial tunnel and femoral tunnel were prepared,and the
      femoral tunnel was a frame of narrow inside and wide outside. The hamstring
      tendons knot and bone bolt were pulled inside of femoral tunnel. The tendons
      distal of tendons knot were brought to pass the femoral tunnel, joint capsule and
      another tibial tunnel. Then, the tendons distal of tendons knot were tightened
      together with the part of hamstring tendons of which the insertion were on tibia.
      After the operation, the knee was fixed at a flexion of 45 degrees by brace.
      RESULTS: The patients were followed up for 8 to 24 months. The function of
      troubled knees was evaluated by Lysholm knee functional scale. The average knee
      score were 61.5 +/- 4.6 and 92.5 +/- 3.7 respectively before and after operation,
      and the difference was statistically significant (P < 0.05). CONCLUSION:
      Hamstring tendons insertion on tibia preserved and an implant fixation technique
      of hamstring tendons knot and bone bolt press-fit was biological fixation for
      anterior cruciate ligament reconstruction with hamstring. The advantage of this
      method was avoidance of using high cost material for fixation,which lessened
      spending for the patients. And it was also benefit for tendon-bone healing.

PMID- 19105383
TI  - [Diagnosis and treatment of the coronal fracture of the femoral condyle].
AB  - OBJECTIVE: To investigate the diagnosis and treatment of the coronal fracture of
      the femoral condyle. METHODS: Seven patients with Hoffa fracture treated in our
      hospital in recent 7 years were enrolled in this study. Six patients were treated
      with surgical treatment, while one non-displaced fracture received conservative
      treatment. Fractures were reduced under direct vision and fixed with hollow lag
      screws. The knees were immobilized in extension with cast after operation, and
      flexion exercise was commenced 3 weeks later. RESULTS: All the patients were
      followed up. According to Kumar functional assessment system,5 patients got
      excellent results, 1 good, and 1 fair. CONCLUSION: Rigid internal fixation with
      hollow lag screw and extension plaster fixation is the excellent way to treat the
      coronal fracture of the femoral condyle.

PMID- 19105384
TI  - [Surgical treatment of ankle fractures under arthroscopy].

PMID- 19105385
TI  - [Treatment of stiffiness of knee joint with arthroscope assisted by little
      incision].

PMID- 19105386
TI  - [Surgical treatment of communited tibial condylar fractures using medial-lateral
      plates with proximal compression bolt and bone graft].

PMID- 19105387
TI  - [Repaire of bone and soft tissue defects in middle and distal leg by using
      retrograde transposition soleus or bone flap].

PMID- 19105388
TI  - [Closed reduction and cannulated screw fixation for the treatment of femoral neck
      fractures].

PMID- 19105389
TI  - [Lateral protrution of lumbar disc: a case report].

PMID- 19105390
TI  - [Clinical experience on the manipulative treatment of cervical frozen shoulder].

PMID- 19105391
TI  - [The research of CT guidance of PVP PKP for osteoporotic thorax compression
      fracture].

PMID- 19105392
TI  - [A randomized controlled trial on calcitriol combined with xianling gubao for the
      treatment of pain caused by osteoporosis].

PMID- 19105393
TI  - [Overview of the classification of distal radius fracture].
AB  - Distal radius fractures are quite common in clinical practice. At present,various
      classification systems of distal radius fractures may cause confusion in
      diagnosis,treatment and evaluating prognosis,which is unfavourable to clinical
      dicision making. We made a conclusion of current classification systems of distal
      radius fracture to assist in guiding treatment.

PMID- 19105394
TI  - [Mass spectrometry methods in metabolomics].
AB  - The review is devoted to metabolomics, a new and rapidly growing area directed to
      the comprehensive analysis of metabolites of biological objects. Metabolites are
      characterized by various physical and chemical properties, traditionally studied
      by methods of analytical chemistry focused on certain groups of chemical
      substances. However current progress of mass spectrometry has led to the
      formation of unified methods, such as metabolic fingerprinting and metabolomic
      profiling, which allow defining thousands of metabolites in one probe. The
      current review describes basic characteristics of these methods, ways of
      metabolite separation, and the analysis of metabolites by mass spectrometry. The
      examples shown in this review, allow to estimate these methods and to compare
      their advantages and disadvantages. Besides that, authors show the methods most
      frequently used in metabolomics for data processing and the required resources,
      such as software for mass spectra processing and metabolite search database. In
      the conclusion, general suggestions for successful metabolomic experiments are
      given.

PMID- 19105395
TI  - [ATP-dependent proteases and proteolytic complexes involved into intracellular
      protein degradation].
AB  - The review characterized the main enzymatic systems of selective proteolysis
      responsible for maintenance of intracellular proteome in prokaryotes, eukaryotes
      and archea. The features of proteolytic components of the ATP-dependent proteases
      as well as similarity and diversity of their regulatory AAA(+)-ATPases are
      discussed.

PMID- 19105396
TI  - [The astacin family of metalloproteinases].
AB  - The review deals with the properties of astacin family of zinc-dependent
      metalloproteinases. One of the remarkable features of these enzymes is their
      ability to cleave peptidyl-arylamides, which is not typical to other
      metalloproteinases. Special attention is paid to physiological functions of the
      astacins and to the influence of domain composition and posttranslational
      modifications on the activity and stability of these enzymes.

PMID- 19105397
TI  - [Matrix metalloproteinase 2 and 9 as the factor of head and neck tumor
      metastasis].
AB  - The levels of metalloproteinases (MMP-2,-9), their tissue inhibitors (TIMP-1,-2)
      and extracellular matrix metalloproteinase inducer (EMMPRIN) were studied in
      tumor tissue and blood serum from patients with head and neck squamous sell
      carcinoma. Immunohistochemical investigation showed much higher expression of MMP
      9 and TIMP-1 in tumor tissue than MMP-2 and TIMP-2. Different expression of the
      studied parameters (except TIMP-1) in cancer cells and stroma was observed.
      Enhanced level of MMP-2,-9 and TIMP-2 expression was revealed mainly in
      fibrocytes, leukocytes and stromal extracellular matrix. Expression of EMMPRIN in
      tumor cells was higher than in stromal cells. It is possible that carcinoma cells
      express EMMPRIN to increase MMP production by surrounding cells. Significant
      decrease of inhibitor expression was observed in cells of carcinomas with N1
      grade of metastasis than in tumors without metastasis. Also the decrease in TIMP
      1 level was determined in blood serum of patients with metastasis to regional
      lymph nodes compared with serum of patients without metastasis. Thus, MMP-9 and
      TIMP-1 play an important role in the development of head and neck squamous sell
      carcinoma and TIMP-1 level in blood serum and cancer tissues is linked to first
      grade of regional lymph node metastasis.

PMID- 19105398
TI  - [Liposomal formulations of protein proteinase inhibitors: preparation and
      specific activity].
AB  - Here we investigated encapsulation of water-soluble proteins into multilayer
      liposomes of soybean zwitterionic phospholipid mixtures (phosphatidylcholine (PC)
      and phosphatidylethanolamine (PE)). The influence of the PC/PE w/w ratio on the
      incorporation efficiency of the Bowman-Birk soybean proteinase inhibitor (BBI)
      and aprotinin (BPTI) into liposomes was studied. Protein encapsulation did not
      affect liposome sizes. Confocal laser scanning microscopy demonstrated that
      proteins were located in the central part of the spherical particle and between
      the bilayers. The biological activity (antitrypsin and antichymotrypsin) assay of
      the protein entrapped in liposomes showed its active sites were spatially
      shielded. The effect of an ionic detergent on the activity of the encapsulated
      BBI and BPTI confirmed this hypothesis and suggested that this shielding is
      reversible. The liposomes stability in three various media-artificial gastric
      juice and intestinal fluids was also examined. The liposomes prepared seem to be
      promising formulations for BBI and BPTI delivery.

PMID- 19105399
TI  - [The influence of LIF (leukemia inhibitory factor) on the functional status of
      mouse line R1 embryonic stem cells].
AB  - The influence of cytokine LIF (Leukemia Inhibitory Factor) on the viability, and
      proliferation of mouse R1 line embryonic stem cells (ESC) and their distribution
      by cell cycle stages has been investigated. LIF (5-20 ng/ml) increased growth of
      colonies and maintained high proliferative and pluripotent properties of R1. LIF
      was also involved into the inhibition of spontaneous cell differentiation and
      apoptotic cell death; it also decreased the rations of S/G2+M cell cycle and
      doubling-time of cell population.

PMID- 19105400
TI  - [Biospecific properties of lysine-contained polyelectrolyte coatings for devices
      contacting blood].
AB  - Biospecific properties of thromboresistant bilayer and multilayer coatings based
      on polyelectrolyte complexes of modified copolymer of N-vinylpyrrolidone and
      maleic acid (VPMA) with chitosan, amphiphilic chitosan or albumin were
      investigated. VPMA contained affinity ligand towards plasminogen--alpha-amino
      coupled lysine residues. Polyethylene and polystyrene surfaces were investigated
      before and after their covering by protective polyelectrolyte coatings. The
      specific adsorption of plasminogen (precursor of the fibrinolytic enzyme plasmin)
      from its solutions and from human plasma was investigated using these model
      systems. It was found that all coatings with the outer contact lay of lysine
      contained affinity polymer had affinity to plasminogen. But multilayer
      polyelectrolyte coatings were more efficient than bilayer coatings with single
      application of layers and the affinity polymer coatings without interlayer. The
      decrease in trombogenicity degree of the materials modified by polyelectrolyte
      coatings was shown in vitro and ex vivo. Emplyment of proposed modification of
      surfaces will improve hemocompatibility of medical devices.

PMID- 19105401
TI  - [Substituted 1,5,6,7-tetrahydro-4H-benzimidazol-4-ones as inhibitors of urease].
AB  - A comparative kinetic study of the inhibition of urea hydrolysis by 9 substituted
      1,5,6,7-tetrahydro-4H-benzimidazol-4-ones (BI I-IX) has been carried out. The
      inhibition had reversibl competitive character; the inhibition constants K(i),
      varied from 29 up to 754 microM in dependence of the structure of BI I-IX. Three
      BI I-III, having the K(i) values from 29 to 82 microM, may be used as the
      potential therapeutic agents for gastroenterology for treatment of stomach and
      duodenal ulcers.

PMID- 19105402
TI  - [Anticoagulant activity of fucoidans from brown algae].
AB  - The anticoagulant activity of polysaccharide fucoidans from 11 species of brown
      algae was studied. The anticoagulant activity was measured by the activated
      partial thromboplastin time (APTT), prothrombin time and thrombin time.
      Inhibitory action of fucoidans varied significantly from one species to another.
      Fucoidans from Laminaria saccharina and Fucus distichus showed high anticoagulant
      activities, while fucoidans from Cladosiphon okamuranus and Analipus japonicus
      were almost inactive. The fucoidan inhibitory effect on thrombin and factor Xa in
      the presence or in the absence of natural thrombin inhibitor, antithrombin III
      (AT III), was also studied. In contrast to the best studied anticoagulant heparin
      the most of the fucoidans inhibited thrombin in the absence of AT III. In the
      presence of AT III inhibitory effect of fucoidans was increased considerably.
      Unlike heparin, the effect of fucoidans on factor Xa was very weak in the
      presence of AT III and was not observed in the absence of AT III. The correlation
      between the anticoagulant activities of this series of fucoidans and their anti
      inflammatory action, studied by us earlier, was not found. It is expected that
      two these types of fucoidan activities depend on different structural features of
      fucoidans. These findings show the possibility to obtain fucoidans with high anti
      inflammatory action and with low anticoagulant activity. Anticoagulant activity
      of the fucoidans did not depend on the content of fucose, the other neutral
      sugars and sulfates in the preparations, and also on the structure of the
      backbone of molecule. Taken together, these results indicate on prospects of
      fucoidan study as potential therapeutic agents.

PMID- 19105404
TI  - [Cerebrovascular diseases in Russia: results and perspectives].

PMID- 19105403
TI  - [The erythrocyte and plasma glutathione system under peptic ulcer].
AB  - In erythrocytes and blood plasma of patients with the complicated peptic ulcer
      and postresectional syndromes there was the increase of conjugated dienes (and in
      the second group the increase in antioxidant activity). Under these conditions
      the main change was the sharp and identical decrease in glutathione activity. In
      patients with uncomplicated peptic ulcer there was sharp increase in erythrocyte
      and plasma glutathione activity and plasma GSH. In operated but basically healthy
      patients plasma glutathione peroxidase remained decreased but plasma GSH sharply
      increased. Evidently complicated peptic ulcer is characterized by decreased
      functioning of the glutathione system. Activation of this system and the decrease
      or disappearance of manifestations of oxidative stress are associated with a
      favorable course of this disease, especially at uncomplicated peptic ulcer. The
      revealed changes significantly differ from those observed in viral hepatitis,
      bile excretory treat diseases and strokes.

PMID- 19105405
TI  - [Tianeptin (coaxil) in therapy of depression in cardiovascular patients].
AB  - AIM: To study clinical efficacy, tolerance and safety of antidepressant coaxil in
      the treatment of patients with cardiovascular disease (CVD) and depression; to
      compare efficacy of combined (somatotropic plus psychotropic) therapy and
      monotherapy with somatotropic drugs in the above diseases. MATERIAL AND METHODS:
      Of 86 participants of the study, 24 had arterial hypertension (AH) and
      depression, 25--AH, coronary artery disease and depression. They received
      combined treatment. 37 patients of the control subgroups received monotherapy.
      Somatic condition of the patients was examined with clinical, device and
      laboratory methods, antidepressant efficiency was examined with the
      clinicopsychopathological method and psychometric scales--HDRS, HARS, MADRS and
      CGI-S. RESULTS: Combined treatment with coaxil provided target blood pressure in
      79.5% patients, monotherapy--in 65.7%. The response in the test subgroups reached
      73.9 and 64.0%. By side effects, the difference between the groups was not
      significant. Somatotropic monotherapy in most control patients failed to reduce
      psychopathological disorders. CONCLUSION: Combined treatment with coaxil proved
      more effective than somatotropic monotherapy in CVD patients with depression.
      Coaxil treatment is safe as it has no side effects.

PMID- 19105406
TI  - [Administration of afobasol for correction of mental disorders in celiac disease
      patients].
AB  - AIM: To study afobasol efficacy in anxiety and neurotization correction in
      patients with celiac disease (CD). MATERIAL AND METHODS: We examined 17 CD
      patients with mental diseases (anxiety, anxiophobic and neurotic disorders) aged
      35.3 +/- 3.5 years. Personal and situational anxiety levels were assessed with
      multivariate questionnaire of the integrative anxiety test, neurotization--with
      Wasserman's questionnaire. Mental diseases were treated for 4 weeks with afobasol
      in a daily dose 30 mg. RESULTS: An initial level of personal anxiety was elevated
      in 100% patients, of situational anxiety--in 66.7%. These kinds of anxiety (most
      of all general, emotional discomfort, asthenic and phobic components) were
      treated with a positive effect. Neurotization was high in 11 patients. The
      treatment was effective in 6 of them. Side effects were not noted. The highest
      reduction was seen in emotional discomfort, asthenic component and anxiety.
      CONCLUSION: Afobasol is effective in management of mental diseases in patients
      with celiac disease.

PMID- 19105407
TI  - [Characteristics of erythrocytes and hemoglobin in patients with ischemic heart
      disease and type 2 diabetes mellitus].
AB  - AIM: To study characteristics of erythrocytes and hemoglobin in patients with
      ischemic heart disease in the presence or absence of concomitant type 2 diabetes
      mellitus (DM) with consideration of clinical symptoms and selective
      coronaroangiographic data. MATERIAL AND METHODS: 287 patients with various forms
      of ischemic heart disease (IHD) were divided into two groups: 226 non-diabetic
      patients (group 1) and 61 type 2 diabetic patients (group 2). The following blood
      parameters were studied: Hb, HCT, red cell count, MCV, MCH, MCHC.
      Electrocardiography, echocardiography, doppler-echocardiography, circadian Holter
      ECG monitoring, bicycle exercise test were made in all the patients,
      coronaroangiography--in 174 patients. RESULTS: Group 2 patients showed
      significantly lower indices of the red blood. Anemia was detected in 38.05 and
      47.62% patients of groups 1 and 2. A highly significant correlation was found in
      both groups between Hb concentration and severity of IHD manifestations (chi
      square 49.06, p < 0.01 and 18.94, p < 0.01 in group 1 and 2, respectively). The
      same correlation was established in group 1 between angina pectoris severity and
      HCT (chi-square 37.912, p < 0.01). ECG registered myocardial ischemia much more
      often in group 2 than in group 1 (52.46 versus 42.48%, respectively). Group 2
      patients with depression of the ST segment had lower red cell level. Diabetic and
      anemic patients had ischemic changes on ECG more frequently, their exercise
      tolerance was less, ectopic activity high. Coronary angiography demonstrated more
      severe affection of the coronary circulation in diabetics. Hb level and the
      latter also correlated (chi-square 24.379, p < 0.01). CONCLUSION: Hemoglobin and
      red cells proved essential in regulation of coronary blood flow and saturation of
      the myocardium with oxygen.

PMID- 19105408
TI  - [Avandia and avandamet in the treatment of patients with diabetes mellitus type
      2: effects on secretion of some fat tissue hormones].
AB  - AIM: To study effects of avandia and its combination with metformine (avandamet)
      on secretion of fat tissue hormones. MATERIAL AND METHODS: The examination
      protocol for 42 patients with type 2 diabetes mellitus (DM) aged 62.4 +/- 7.7
      years comprised tests for blood levels of leptin, soluble receptor to leptin,
      insulin, grelin, resistin and adiponectine. RESULTS: The treatment resulted in
      reduction of fasting glycemia from 10.69 +/- 2.54 to 8.42 +/- 1.73 mmol/l, of
      glycosilated hemoglobin--from 8.1 + 1.6 to 7.75%, immunoreactive insulin--from
      19.1 +/- 8.3 to 12.0 +/- 6.5 mg/ml, grelin--from 21.7 +/- 14.6 to 17.3 +/- 13.7
      mg/ml, leptin--from 40.3 +/- 24.2 to 26.9 +/- 15.4 mg/ml, soluble receptor to
      leptin--from 17.9 +/- 4.5 to 13.1 +/- 3.5 mg/ml. LDLP and HDLP cholesterol was
      high. CONCLUSION: Avandia and avandamet are effective antidiabetic drugs with a
      beneficial effect on secretion of fat tissue hormones.

PMID- 19105409
TI  - [Mildronate effects on oxidant stress in type 2 diabetic patients with diabetic
      peripheral (sensomotor) neuropathy].
AB  - AIM: To clarify mildronate effects on oxidant stress and tissue oxygen in
      combined treatment of peripheral (sensomotor) neuropathy in patients with type 2
      diabetes mellitus (DM). MATERIAL AND METHODS: An open randomized trial
      investigated 70 matched patients with type 2 DM and sensomotor neuropathy. They
      were randomized into two groups. The study group received basic anti-diabetic
      treatment, alpha-lipoic acid and mildronate for 3 months. Patients of the control
      group received the same treatment but mildronate. RESULTS: Mildronate
      administration improved clinical condition of the study group patients vs
      controls by neuropathy and symptoms count scales, electrophysiological properties
      of the nerve fibers, optimization of oxygen tissue balance, reduced production of
      lipid peroxidation products and activated enzymes of antioxidant defense.
      CONCLUSION: It is recommended to add 1 g/day mildronate to standard schemes of
      treatment for diabetes and sensomotor neuropathy.

PMID- 19105410
TI  - [Morphofunctional characteristics of neutrophils in patients with autoimmune
      thyroiditis].
AB  - AIM: To study morphofunctional status of neutrophilic polymorphonuclear
      leukocytes (NPNL) in patients with chronic autoimmune thyroiditis (CAIT).
      MATERIAL AND METHODS: The morphofunctional status of NPNL was investigated with
      vital computer phasic morphometry (CPM) in 25 patients (24 females and 1 male,
      mean age 45.4 +/- 3.2 years) with verified CAIT and 20 healthy females. Solid
      phase enzyme immunoassay examined the serum for IL-8 content. RESULTS: CAIT
      patients have characteristic features of neutrophil morphofunctional state
      (changed cell size, disproportion in population morphological structure), IL-8
      level was 13.9 fold higher than normal--63.8 pg/ml. CONCLUSION: CAIT patients
      demonstrate activation of the mechanisms which regulate cell nonspecific
      resistence. As a result, locomotor, secretory and phagocytic NPNL functions
      enhance. Changes detected may reflect severity of the pathological process and
      indicate growing autoaggression in CAIT patients.

PMID- 19105411
TI  - [Arrhythmia and vegetative imbalance in hypothyrosis patients].
AB  - AIM: To examine disturbances of cardiac rhythm and effects of autonomic nervous
      system on cardiovascular system in hypothyrosis patients as shown by circadian
      ECG monitoring. MATERIAL AND METHODS: A total of 171 patients with primary
      hypothyrosis (11 males, 160 females, mean age 56.2 +/- 4.8 years) were examined
      with circadian ECG monitoring. The patients were divided into two groups by the
      degree of hypothyrosis compensation. Group 1 (n = 87) had primary hypothyrosis in
      decompensation (TTH 14.78 +/- 1.3 mIU/l), group 2 (n = 84) had compensated
      hypothyrosis treated with sodium levothyroxin as replacement therapy (TTH 1.32 +/
      0.3 mIU/l). RESULTS: It was found that group 1 patients have bradycardia,
      subnormal circadian index, prolonged corrected interval Q-T, inhibition of
      atrioventricular conduction, increased number of supra- and ventricular
      extrasystoles, predominance of the parasympathetic autonomic nervous system in
      regulation of heart rhythm. CONCLUSION: Decompensated hypothyrosis is accompanied
      with significant disorders of cardiac activity and imbalance of autonomic nervous
      system which are corrected in hypothyrosis compensation.

PMID- 19105412
TI  - [Lisinopril: antihypertensive activity, effects on heart rhythm variability and
      carbohydrate metabolism in patients with metabolic syndrome].
AB  - AIM: To examine antihypertensive activity, heart rate variability (HRV) and
      carbohydrate metabolism of ACE inhibitor lisinopril in patients with metabolic
      syndrome (MS). MATERIAL AND METHODS: Twenty MS patients (13 females and 7 males)
      received lisinopril monotherapy for 12 weeks. Before the treatment and after 12
      weeks of lisinopril treatment the following tests were made: office measurement
      of blood pressure (BP), 24-hour BP monitoring, exercise test, investigation of
      HRV and carbohydrate profile. RESULTS: A 12-week treatment with lisinopril had
      high antihypertensive efficacy, its positive action on HRV and carbohydrate
      metabolism manifested in reduction of postprandial glycemia and insulinemia.

PMID- 19105413
TI  - [Metabolic syndrome and chronic disease of the kidneys: the role of age-related
      androgenic deficiency. New approaches to treatment (review)].

PMID- 19105414
TI  - [Erectile dysfunction as an ignored component of the history of a therapeutic
      patient: current view and practice].

PMID- 19105415
TI  - [Botulinum A toxin in the treatment of patients with detrusor external sphincter
      dyssynergia and neurogenic low detrusor contractility].
AB  - AIM: To investigate safety and efficacy of botulinum A toxin external urethral
      sphincter injection in the treatment of patients with detrusor external sphincter
      dyssynergia (DSD) and neurogenic low detrusor contractility (DC). MATERIAL AND
      METHODS: The study included 21 patients with DSD and 27 patients with low DC
      between 17 and 73 years of age. The diagnostic scheme consisted of voiding diary
      for 72 hours, laboratory tests, ultrasound investigation with measurement of
      residual urine volume, urodynamic investigation and neurologic examination. 100
      units of botulinum A toxin (botox, allergan) were injected into external urethral
      sphincter paraurethrally in women and transurethrally in men. RESULTS: 6 months
      after the toxin injection good results were achieved in 6 out of 9 DSD patients
      with spontaneous micturition; physiologic micturition was restored in 5 out of 8
      patients who had performed intermittent self catheterization and in 3 out of 4
      patients with suprapubic fistula and urethral catheter. As for patients with
      neurogenic low DC, good results were achieved in 6 of 8 patients who had had
      spontaneous micturition; physiologic micturition was restored in 13 out of 14
      patients who had performed intermittent self catheterization and in 3 out of 5
      patients with suprapubic fistula and urethral catheter. There were neither
      complications nor side effects. CONCLUSION: Botulinum A toxin external urethral
      sphincter injection demonstrated high efficacy in patients with DSD and
      neurogenic low DC.

PMID- 19105416
TI  - [Experience with velcade administration in multiple myeloma].
AB  - AIM: To study efficacy of velcade therapy for progressive or resistant multiple
      myeloma (MM). MATERIAL AND METHODS: We used velcade in therapy of 36 patients (18
      males and 18 females, age 43-76, age median 58 years) with progressive or
      resistant MM from April 2006 to February 2008. Prior second line standard therapy
      failed. A total of 206 courses of treatment were performed. RESULTS: Treatment
      outcomes were assessed in 34 patients, 2 patients continue treatment. Overall
      response was 55.9% (EBMT criterion). A complete, partial and minimal responses
      were achieved in 10, 4 and 5 cases, respectively. No response was observed in 11
      patients. Velcade was administered in polyresistance to polychemotherapy (PCT)
      programs including VAD (5 patients), contraindications for PCT because of old age
      or comorbid pathology (13 patients). These patients received 1-9 courses of
      velcade (as monotherapy in 28 patients, in combination with high-dose
      dexamethasone in 6 patients, in combination with high-dose dexamethasone and
      doxorubicin in 3 patients with progressive disease). Follow-up of this group from
      the start of velcade therapy was 4-15 months. Velcade induced stabilization of
      the disease in 4 patients (follow-up median was 8 months), progression of the
      disease in 5-9 months occurred in 6 patients.

PMID- 19105417
TI  - [The 50th anniversary of the Institute of Rheumatology].

PMID- 19105418
TI  - [Subclinical and clinical manifestations of atherosclerosis in antiphospholipid
      syndrome].
AB  - AIM: To evaluate intima-media complex (IMC) thickness in patients with
      antiphospholipid syndrome in terms of clinical-laboratory manifestations and
      thrombosis risk factors. MATERIAL AND METHODS: The trial included 206 patients
      (57 males and 149 females, age 16-59, mean age 35.9 years). Of them, 58 (28%)
      patients had primary antiphospholipid syndrome (PAPS) alone, 148 had documented
      concomitant systemic lupus erythematosus (SLE). Seventy two (48.6%) SLE patients
      had antiphospholipid syndrome (APS), 29 (19.6%)--anticardiolipin antibodies (aCL)
      level above 40 IU in two and more measurements without clinical symptoms of APS.
      In addition to standard tests, APL (lupus anticoagulant), aCL and antibodies to
      beta-2 glycoprotein, blood lipids were measured. Thrombosis and atherothrombosis
      risk factors were evaluated. Ultrasound dopplerography estimated thickness of IMC
      in the carotid and femoral arteries. The control group consisted of 89 donors
      free of autoimmune diseases. RESULTS: Mean values of IMC thickness did not differ
      between the groups. Atherosclerotic plaques (ASP) were detected in 25 (12%) of
      206 patients: in 5 (9%) from PAPS group, 10 (14%) from SLE+APS, in 4 (14%) and 6
      (13%) from SLE groups aPL+ and aPL-, respectively. Mean age of patients with ASP
      was 46 +/- 6.9 years (32-55 years). ASP occurrence was associated with older age:
      ASP were detected in 10 (38%) of 26 patients aged over 51 years (24 plaques), in
      10 (20%) of 50 patients aged 41-50 years (18 plaques) and in 5 (10%) of 50
      patients aged 41-50 years (18 plaques) and in 5 (10%) of 50 patients aged 31-40
      years (9 plaques, p = 0.001). IMC thickness and plaques were associated with
      prior arterial and venous thromboses and occurred significantly more frequently
      in patients with myocardial infarction and transient ischemic attacks (p <
      0.001). Thrombosis and atherothrombosis risk factors were associated with changed
      IMC thickness. The level of aPL and their type had no effect on IMC thickness and
      ASP incidence in the groups studied. CONCLUSION: Increased IMC thickness was
      associated with age irrespective of APS presence. In SLE, ASP appeared at younger
      age than in PAPS patients. Atherothrombosis risk factors affect IMC thickness
      irrespective of the level and type of aPL.

PMID- 19105419
TI  - [Endothelial dysfunction in scleroderma systematica: clinicopathogenetic
      correlations].
AB  - AIM: To evaluate disturbances of vascular tonicity regulation in scleroderma
      systematica (SS) patients using laser Doppler flowmetry (LDF) with calculation of
      amplitude-frequency blood flow fluctuations (variability) basing on the
      mathematical model wavelet-transformation. MATERIAL AND METHODS: The trial
      included 101 patients with verified SS aged 21-60 years (mean 52.3 years, 97
      females). In addition, 15 and 10 patients with primary and secondary Raynaud
      syndrome diagnosed by ACR criteria, respectively, entered the trial. The control
      group consisted of 20 healthy subjects. Cardiovascular patients were not included
      in the study. Microcirculation was investigated with laser analyzer of capillary
      circulation in the tip of left hand finger III and external surface of the left
      arm. Endothelial motor function was studied in the tests with reactive hyperemia
      and nitroglycerin. RESULTS: SS patients were found to have a significantly higher
      variability and endothelial rhythm amplitude index in arm skin, reduced
      microcirculation, the variation index and high neurogenic tonicity in the hand
      finger tip. A direct correlation was found between severity and area of skin
      lesion (of the arm, in particular) and their amplitude of endothelial
      fluctuations (r = 0.38, p = 0.03) of circulation in the arm skin. Persistent
      correlations between skin count and LDF values were not registered. There was a
      significant regression of flow-dependent dilation of the brachial artery in SS
      patients independent of classic cardiovascular risk factors. CONCLUSION: SS
      patients have defects in regulation of vascular tonicity both in microcirculation
      and middle-caliber arteries. Vasomotor activity of the middle-caliber vessels is
      low in the absence of conventional cardiovascular disease risk factors. LDF
      detects changes in local regulation in cardiovascular patients confirming the
      role of neuroendothelial disorders in its pathogenesis. The trend to systemic DE
      in cardiovascular patients is associated with both disease-mediated vascular
      lesions (ulcers of finger tips, pulmonary hypertension) and cardiovascular
      disease markers.

PMID- 19105420
TI  - [Anticitrulline antibodies and wrist joint MRI parameters in patients with early
      arthritis].
AB  - AIM: To examine correlations between immunological markers, clinical parameters
      and MRI data in patients with early rheumatoid arthritis (RA) and
      undifferentiated arthritis (UDA). MATERIAL AND METHODS: The study was made of 211
      patients with early RA (43 males, 168 females) and 47 patients with early UDA
      (mean age 48.6 +/- 13.4 years), duration of the symptoms 5.5 +/- 4.5 months). RF
      positive were 136 (64.5%) patients. X-ray erosions were detected in 45 (21.3%)
      patients. RA activity was estimated by the integral DAS28 index (by 3
      parameters), function--by HAO questionnaire (Russian version). The
      immunonephelometric analyzer (BN-100, Dade Behring, Germany) determined
      concentration of C-reactive protein (CRP), IgM. Anticitrulline antibodies (ACAB)
      were estimated by enzyme immunoassay, the upper limit of the norm was 5.0 U/ml.
      MR imaging (MRI) of both the wrists in RA patients was made on the 0.2 T Artoscan
      unit, the assessment was made with the reference atlas OMERACT-RAMRIS. RESULTS:
      IgM and ACAB levels were much higher in RA than in UDA. Among the patients
      positive by both tests (RF+ACAB) 95.2% had a typical clinical picture and RA
      diagnosis while 60% patients negative by RF and ACAB had UDA (p < 0.001); among
      patients positive by one of the tests the ratio UDA to RA was 1:2 (32.6 and
      67.4%). In RA patients with very high ACAB (> 100 U/ml) CRP reached 38.10 +/-
      48.29 mg/l while in negative ACAB--17.07 +/- 19.34 mg/l (p = 0.016). Wrist MRI
      detected synovitis and bone erosions in 93 and 66% cases, respectively. High ACAB
      level (> 100 U/ml) and CRP levels were associated with high DAS28, RF IgM and MRI
      erosions number. CONCLUSION: RF and ACAB patients are characterized by a typical
      RA picture in the disease onset (specificity 93.6%). MRI detects synovitis in the
      wrist joints in 93 and erosions in 66% early RA patients. Combination of high
      ACAB and CRP levels is associated with high RA activity, RF IgM and great number
      of erosions according to MRI and may serve a marker of a severe disease course.

PMID- 19105421
TI  - [HIV-1 protease inhibitors: cell metabolism and drug resistance (review)].

PMID- 19105423
TI  - [Current approaches to diagnosis and treatment of psoriatic arthritis (review)].

PMID- 19105422
TI  - [Do patients over 80 years of age benefit from antihypertensive treatment? Look
      for the answer in the results of HYVET trial (lecture)].

PMID- 19105424
TI  - [The role of ossein-hydroxyapatite complex in osteoporosis prophylaxis (review)].

PMID- 19105425
TI  - [Persistent remission of Takayasu aortoarteritis induced by long-term treatment
      with infliximab and confirmed by repeat positron emission tomography].

PMID- 19105426
TI  - [Potentialities of positron emission tomography in diagnosis and control of
      efficacy of giant cell arteritis treatment].

PMID- 19105427
TI  - [Reconstruction of anterior cruciate ligament with hamstring tendon autografts
      under arthroscopy].
AB  - OBJECTIVE: To evaluate therapeutic effects for reconstruction of anterior
      cruciate ligament(ACL)with hamstring tendon autografts and bioabsorbable
      interference screws fixation under arthroscopy. METHODS: Thirty-one patients with
      ACL rupture were verified through arthroscopy. There were 27 patients were male
      and 4 patients were female, ranging in age from 17 to 40 years,with an average of
      25 years. Among the patients, 26 patients combined with meniscus injuries, 3
      patients with injuries of articular cartilage and 16 patients with I to II degree
      degeneration of articular cartilage. All the patients were performed ACL
      reconstruction with hamstring tendon autografts under arthroscopy and the
      reconstructed ligaments were fixed with bioabsorbable interference screws.
      RESULTS: No severe complications occurred at early stage after operation. Thirty
      patients were followed up and ranged from 9 to 39 months,with an average of (19
      +/- 9.0) months. Lysholm score significantly increased from average of 54.6 +/-
      16.6 preoperatively to average of 92.5 +/- 5.7 at the end of follow-up period (t
      = 11.84, P < 0.01). Twenty-six patients restored to normal activity. CONCLUSION:
      ACL reconstructed with hamstring tendon autografts under arthroscopy has
      advantages of minimal trauma and satisfactory outcomes.

PMID- 19105428
TI  - [Observation on therapeutic effects of electroacupuncture for the treatment of
      knee osteoarthritis].
AB  - OBJECTIVE: To study the therapeutic effects of electroacupuncture for the
      treatment of osteoarthritis of knee joint. METHODS: Forty patients with knee
      osteoarthritis were randomly divided into two groups: the electroacupuncture
      group (20 patients)and the control group (20 patients). The patients in
      electroacupuncture group (8 male and 12 female, with an average age of 62.50 +/-
      9.23 years and mean course of disease 9.85 +/- 8.17 years)were treated with
      electroacupuncture for one month. At the same time, the patients in control group
      (7 male and 13 female, with an average age of 61.15 +/- 6.75 years and mean
      course of disease 8.60 +/- 6.89 years) were given Diclofenac sodium orally for
      one month. The motor function of knee joints were evaluated before and after
      treatment according to Lysholm knee scoring scale. RESULTS: Most scores in the
      electroacupuncture group improved significantly compared with those of before
      treatment (P < 0.01 or P < 0.05) except for the item demands for support. While
      in the control group, compared with those of before treatment, there were
      significant difference on the item of pain, inter locking and instability (P <
      0.01 or P < 0.05), but there were no significant differences on other five items
      (P > 0.05). Between the two groups after treatment, differences on item of inter
      locking, instability, swelling, stair activity and squat were significant (P <
      0.05), but no differences on limp, demands for support and pain (P > 0.05).
      CONCLUSION: Acupuncture can effectively improve the clinical symptoms and knee
      joint's motor function of patients with knee osteoarthritis, and more superior
      than Diclofenac sodium oral. It is a proved effective method for osteoarthritis.

PMID- 19105429
TI  - [Prevention of prothesis dislocation after the revision of total hip
      arthroplasty].
AB  - OBJECTIVE: To explore the role of reconstruction of the posterior capsule and
      external rotators in prevention of postoperative dislocation in total hip
      arthroplasty revision following the posterolateral approach. METHODS: Forty-five
      patients (47 hips) with the mean age of 65 years (55 to 78 years)of failed total
      hip arthroplasty were revised following the posterolateral approach. Posterior
      capsule was sutured to the anterosuperior portion of the capsule from where it
      had been detached, and the external rotators were then reattached to the soft
      tissue at the tip of the greater trochanter using 1.0 silk suture in surgery. The
      dislocation rate and risk factors were reviewed retrospectively to determine if
      closing the posterior capsule resulted in fewer dislocations. The femoral
      prosthesis and acetabular prosthesis were revised in 29 patients (31 hips), the
      liner was exchanged in 5 patients (5 hips), and the acetabular prosthesis or
      femoral components were revised in 10 patients (10 hips) and one patient (one
      hip) respectively. The procedure was the patient's first revision in 29 patients
      (30 hips), the second revision in 15 patients (16 hips), and the third revision
      in one patient(one hip). Radiographic evaluation included lower limb discrepancy,
      acetabular phase, femoral offset, anteversion angle, prosthetic loosening before
      and after revision. Function evaluation based on Harris score system. RESULTS:
      All patients were followed up with an average of 2.7 years. None of the patients
      sustained dislocation or infection, except one patient felt the anterior
      instability but without dislocation, X-ray revealed the acetabular component was
      in excessively anteversion. Lower leg discrepancy, acetabular abduction,
      anteversion femoral offest and collodiaphyseal angle were restored to normal
      level after operation on the basis of X-ray. One of the acetabular components and
      one of the femoral components were loose without dislocation. The Harris hip
      score improved from (49.13 +/- 15.53) points preoperatively to (83.59 +/- 6.93)
      points at the final follow-up (P < 0.05). According to Harris functional
      evaluation, 36 hip got an excellent result, 5 good, 5 fair and 1 bad. CONCLUSION:
      The historically high dislocation rate with the posterolateral approach for total
      hip arthroplasty revision can be reduced by careful soft tissue
      balancing,correction of implant alignment, meticulously closure of the posterior
      capsule, and reattaching the external rotators.

PMID- 19105430
TI  - [Treatment of fractures of tibia intercondylar eminence under arthroscopy using
      suture anchors].
AB  - OBJECTIVE: To explore a new technique of reduction and internal fixation for
      tibia intercondylar eminence fractures under arthroscopy. METHODS: From June 2004
      to February 2006, 9 patients with fresh tibia intercondylar eminence fracture
      (type II in 4 cases and type III in 5 cases) were treated with reduction and
      internal fixation using suture anchors (Depuy Mitek) under arthroscopy. All the
      patients, subject to regular post-operation functional exercise, were followed up
      for 6 to 22 months. The results were evaluated in the aspects of fracture
      reduction healing, knee joint relaxation and ROM, and functional restoration of
      overall limbs. RESULTS: In the nine patients, the tibia intercondylar eminence
      fractures healed without displacement and nonunion. No knee joint relaxation or
      extension-restriction was found. Lysholm score indicated 93.8 +/- 2.3 at the 6th
      postoperative months. CONCLUSION: The reduction and internal fixation of tibia
      intercondylar eminence fractures under arthroscopy using suture anchors
      demonstrate a reliable and easy-to-use technique. Operation under arthroscopy
      helps diagnose and treat other complications inside knee joint, merely resulting
      in slight injury. In addition,early functional exercise contributes to rapid
      recovery of knee joint's functions.

PMID- 19105431
TI  - [Training of Taoism kungfu in Mt. Tiantai and bone setting manipulation].

PMID- 19105432
TI  - [Clinical randomized controlled trial on splint external fixation combined with
      Chinese herbs in treating distal radius fractures of elderly patients].
AB  - OBJECTIVE: To explore the effects of Yishen Zhuanggu decoction ([Chinese
      characters: see text], YSZGD) on the fracture healing and function of wrist joint
      in osteoporotic distal radius fractures (ODRF) of elderly patients. METHODS:
      Ninety patients of ODRF were treated with splint external fixation and YSZGD,
      including 28 males and 62 females, with an average age of 63 years (ranged, 61 to
      91 years). According to AO classification, all the patients were classified as
      type A or B1. Among the patients, 80 patients had a type of Colles fracture,7
      patients were with a type of Smith fracture,and 3 patients had a type of Barton
      fracture. They were randomly divided into three groups included TCM, Western
      medicine and control group (30 cases each group) after the fractures were fixed
      manually by splint. Patients in TCM group took YSZGD orally, one potion and two
      time each day; the patients in Western medicine group treated with Calcitonin (50
      units, intramuscular, 2 times each week), Caltrate D (1 tablets, taken orally,
      one time each day) and Alfacalcidol Soft Capsules (0.5 units, taken orally, one
      time each day); and the patients in control group took no medicine. X-ray
      examination on the fractured wrist was taken at the 4, 6, 8, 12th weeks after
      treating to observe, the fracture healings, the evaluation of wrist function and
      comparision of curative effects were taken at the 2nd month. RESULTS: The
      fracture healing time in TCM group was 7.12 +/- 2.32 weeks and that in the
      Western medicine group was 9.25 +/- 3.05 weeks, showing significant differences
      between them (PC < 0.05), and that in the control group was 11.57 +/- 1.93 weeks
      which was longer thant in that in the two medicine groups (P < 0.05); According
      to Dienst wrist rating system, the excellent and good rates of three groups were
      93.3%, 86.7% and 60% respectively which showing significant differences between
      medicine groups and control group (P < 0.05), and the curative effects of
      medicine groups were more excellent than that of control group through Ridit
      analysis. CONCLUSION: YSZGD can promote the fracture healing evidently and
      shorten the healing time, whose curative effect surpassed Western medicine and
      promoted the restoration of wrist function.

PMID- 19105433
TI  - [Effects of femoral offset on soft tissue balance in total hip arthroplasty].
AB  - OBJECTIVE: To analysis the effects of restoring neck length and femoral calcar of
      femoral component on the reconstruction of femoral offset and its affection on
      soft tissue balance in total hip arthroplasty with standard femoral components.
      METHODS: Sixty-eight patients (71 hips, 30 male and 38 female,ranging in age from
      17 to 89 years,with an average of 63.5 years)undergone primary total hip
      arthroplasty were followed up. The postoperative hip scored according to Harris
      hip score symtem, and femoral offset,femoral calcar restored as well as neck
      length of femoral component were measured from the postoperative X-ray image, and
      the adductor muscle force was measured by Cybex-6000 isokinetic muscle strength
      testing system. RESULTS: Femoral neck length had highly significant and positive
      correlation with femoral offset (r = 0.64, P < 0.001), and had more effects on
      femoral offset than restoring femoral calcar (t = 3.07, P < 0.01), but had no
      significant difference on postoperative Harris score. The postoperative femoral
      offset of patients operated for the femoral head osteonecrosis was less than
      those for the hip osteoarthrosis (t = 2.91, P < 0.01) and the femoral neck
      fracture (t = 3.31, P < 0.01). The adductor muscle force in patients who restored
      femoral offset were better than those failed to restore femoral offset.
      CONCLUSION: There are several factors affecting femoral offset restoration for
      soft tissue balance in total hip arthroplasty with standard femoral components,
      among them, the key factor is the neck length of femoral component which is more
      significant than femoral calar restoration for reconstruction of femoral offset.
      The role of femoral offset on soft tissue balance in total hip arthroplasty was
      strengthening the postoperative adductor muscle.

PMID- 19105434
TI  - [Effects of Astaxanthin on the damage of osteoblast induced by H2O2].
AB  - OBJECTIVE: To investigate the effect of Astaxanthin on enhancing the function of
      anti-oxidative damage in osteoblast. METHODS: MC3T3-E1 osteoblasts were randomly
      divided into five groups, including control group, model group, Astaxanthin group
      [low-dose (1 x 10(-7) mol/L), middle-dose (1 x 10(-6) mol/L), high-dose (1 x 10(
      5) mol/L)], in which the activity of cells, activity of superoxide dismutase
      (SOD), the content of reactive oxygen species (ROS), lipid oxygen (LPO) and
      membrane fluidity were tested and compared. RESULTS: Compared with Astaxanthin
      groups, the activity of cells, SOD activity and membrane fluidity in the model
      group were significantly decreased (P < 0.01). However, the contents of ROS and
      LPO were significantly raised (P < 0.01). CONCLUSION: H2O2 can cause oxidative
      damage of MC3T3-E1 osteoblasts, but Astaxanthin can prevent or decrease its
      influence.

PMID- 19105435
TI  - [Experimental study on the effects of pharmaco-serum of diabetic rats fed with
      Chinese herbs qianggubao decoction ([Chinese characters: see text]) on osteoblast
      culture in vitro].
AB  - OBJECTIVE: To investigate the optimum phase and dose of pharmaco-serum of
      diabetic rats fed with Qianggubao decoction ([Chinese characters: see text]) on
      the differentiation and mineralization of osteoblast (OB). METHODS (OB) was
      isolated from the skull of 10 newly born SD rats aged 1 to 2 days by means of
      Trypsin-collagenase digestion. After the OB was identified, different kinds of
      pharmaco-serum of diabetic rats fed with inactive Qianggubao decoction ([Chinese
      characters: see text]) of different phase (rats were fed with medicine three days
      or five days after last fed with medicine one hour or three hours) and
      concentration (5%, 10%, 20%) were added to the OB and incubated. After 7 days and
      18 days of culture,the effects of the differentiation and mineralization of
      osteoblast were detected. RESULTS: The secretion of ALP and formation of
      mineralized nodules of osteoblast in the different doses of pharmaco-serum groups
      were almost the same as that of normal control group, but were superior to that
      in the model control group. And the group with concentration of 20% pharmaco
      serum was the best in the secretion of ALP and formation of mineralized nodules
      of osteoblast. As to the phases of pharmaco-serum, the best one on the
      differentiation and mineralization of osteoblast was the serums from diabetic rat
      model fed with Qianggubao decoction ([Chinese characters: see text]) three days
      or five days, after one hour of last fed with medicine. CONCLUSION: The pharmaco
      serum of diabetic rats fed with Qianggubao decoction ([Chinese characters: see
      text]) can promote the differentiation and mineralization of osteoblast. Allow
      for time and the cost of experiment,we presume that pharmaco-serum of diabetic
      rats fed with Qianggubao decoction ([Chinese characters: see text]) three days,
      after one hour of last fed, with concentration of 20% and not-inactivation is the
      optimum on the differentiation and mineralization of osteoblast.

PMID- 19105436
TI  - [Relationship between the gray level of X-ray photograph and the cortical
      thickness].
AB  - OBJECTIVE: In order to get three dimensional measurements simply an plain X-ray
      photographs. METHODS: The multi-layers of bone pieces were made by use of bone
      saw, and piled up to spiral ladder, which was used as a calibrating module for to
      living bone in clinics. The relationship between the cortical thickness and gray
      level of the X-ray photographs was obtained. RESULTS: The correlation can be
      described with a cubic regression curve, and it can be simplified to a linear
      regression equation when cortical thickness is small than 3.8 mm. CONCLUSION: It
      can be realized to get three dimensional measures of the bone on plain X-ray
      photographs, by use of the bony spiral ladder described here.

PMID- 19105437
TI  - [Study on change of metabolism of articular cartilage in ovariectomized rats in
      the intervention of different drugs].
AB  - OBJECTIVE: To study the influence of metabolism of articular cartilage in
      ovariectomized rats in the intervention of different drugs. METHODS: Sixty-six
      virgin female Sprague-Dawley rats were randomly stratified into six groups: sham
      operation (SHAM) group,ovariectomized (OVX) group, estrogen replacement therapy
      (ERT) group, estrogen receptor modulator (ERM) group, Xianling Gubao([Chinese
      characters: see text], XLGB) group,and glucosamine sulfate (GS) group. One group
      subjected to standard sham operation and the remaining five groups were
      ovariectomized. The five ovariectomized groups received treatment either with the
      vehicle or different drugs given as an oral suspension in the vehicle. Urine
      samples were obtained at initial time and weeks 3, 5 and 7 after ovariectomy.
      ELISA method was used to measure the concentration of collagen II degradation
      products (CTX-II) in the urine. At study termination,histological analysis of the
      knee joint was used to assess the pathological changes of the articular
      cartilage. RESULTS: Compared with the baseline, the concentration of CTX-II at
      weeks 3 and 5 after ovariectomy were obviously different (P < 0.05). Compared
      with the OVX group, concentration of CTX-II in the ERT group and ERM group were
      significant different (P < 0.01). XLGB group also was obviously different with
      the OVX group at the two points (P < 0.05). And interestingly in the histological
      examination in the OVX group was different with all the other groups. CONCLUSION:
      The study indicates that estrogen deficiency accelerates destructive turnover of
      the collagen II in articular cartilage. The ERT, ERM, XLGB can relieve the
      effect. And all the drugs can delay the cartilage degradation caused by that
      effect.

PMID- 19105438
TI  - [Clinical studies on postoperative rehabilitation for total hip replacement].

PMID- 19105439
TI  - [Rotational alignment in total knee arthroplasty].
AB  - Patellofemoral complications are the most common complications after total knee
      arthroplasty. The rotational alignment of the femoral component during operations
      is related to the occurrence of the patellofemoral complications, and is
      extremely important for the clinical outcomes of total knee arthroplasty.

PMID- 19105440
TI  - [Examination and surgical treatment of lost instability of traumatic dislocation
      of the knee joint].
AB  - OBJECTIVE: To study the examination,surgical opportunity and surgery methods of
      lost instability of traumatic dislocation of the knee joint. METHODS: Sixty-three
      patients (48 males and 15 females,ranging in age from 16 to 75 years,with an
      average of 36.6 years) were checked, treated and followed up from January 2001 to
      April 2006. According to classification of Wascher for knee dislocation, there
      was 1 case of KD-I, 13 KD-II, 17 KD-III, 18 KD-IV, 14 KD-V. Stability of the knee
      was evaluated by physical and radiological examinations, of which 53 patients
      were treated with open surgery, 4 patients were treated with arthroscope, 4
      patients were treated with arthroscope and open surgery, 1 patient was treated
      with amputation, 1 patient was treated with total knee arthroplasty. RESULTS: The
      detection rate of MRI was 100% (39/39), stress radiography was 100% (19/19),
      arthroscpoe was 93.3% (14/15). According to Lysholm Criteria for knee joint
      function,the preoperative Lysholm score in old traumatic group was 37.17 +/-
      5.33, fresh traumatic group was 37.41 +/- 5.38. The postoperative Lysholm score
      in old traumatic group was 67.33 +/- 14.72, fresh traumatic group was 82.45 +/-
      12.13 (Z = -3.061, P = 0.002). CONCLUSION: MRI stress radiography and arthroscope
      do well for the evaluation of stability of the knee. Instable traumatic
      dislocation of the knee joint must be operated promptly. Fresh instable
      dislocations of knee prefer repair,old instable dislocations of knee prefer
      reconstruction.

PMID- 19105441
TI  - [Advances in CT classification and outcomes assesment of calcaneus fractures].

PMID- 19105442
TI  - [High tibial osteotomy for the treatment of osteoarthritis of the knee].
AB  - OBJECTIVE: To summarize clinical application of the high tibial osteatomy (HTO)
      with lateral closing-wedge for the treatment of pain of unicompartmental
      osteoarthritis of the knee. METHODS: From February 2000 to February 2004,9
      patients (3 males and 6 females, ranging in age from 52 to 58 years, with an
      average of 56 years) with unicompartmental osteoarthritis of the knee treated by
      HTO with lateral closing-wedge. The proximal tibiofibular joint was exposed, the
      anterior part of the capsule was incised, and to remove a laterally based wedge
      with saw cuts and osteotomes. Stepped staples were used for the fixation of
      tibial osteotomies after closing the defect of osteotomy. RESULTS: The operative
      course was uneventful. There were no complications after operation. The
      postoperative follow-up period ranged from 2 to 5.5 years (mean, 3.5 years). The
      results were evaluated with functional assessment criterion of the osteoarthritis
      of the knee, among the 9 cases, excellent was in 5 cases, good in 3 cases, fair
      in 1 case. CONCLUSION: HTO with lateral closing-wedge is an effective operative
      method for the treatment of pain of unicompartmental osteoarthritis of the knee,
      but except for older patients over 60 years.

PMID- 19105443
TI  - [Technology of minimally invasive percutancous plate osteosynthesis for the
      treatment of fractures of the distal tibia].
AB  - OBJECTIVE: To explore the technique and clinical results of minimally invasive
      percutancous plate osteosynthesis (MIPPO) for the treatment of fractures of the
      distal tibia. METHODS: A retrospective study was conducted to analyze 65 patients
      with the distal tibia fractures who had been treated with MIPPO. The average age
      of the patients was 35 years old (ranging from 13 to 75). There were 42 males and
      23 females. According to AO fracture classification for the distal tibial
      fractures, there were 5 cases of type-A1 fracture, 22 type-A2, 32 type-A3 and 6
      type-C1. RESULTS: All the patients were followed up and ranged from 6 to 18
      months (averaged 11 months). All the fractures showed union. The time required
      for the bony union ranged from 3 to 6 months (averaged 4.5 months). The patients
      were evaluated with respect to functional recovery according to Mazur Grating
      System for the Ankle. Forty patients obtained excellent results, 19 good and 6
      fair. The total satisfactory rate was 90.7%. CONCLUSION: The technology of
      minimally invasive percutancous plate osteosynthesis (MIPPO)is a safe and
      effective procedure for the distal tibial fractures with the benefits of limited
      invasion,less complications and high rate of bone union.

PMID- 19105444
TI  - [Percutaneous suture in the treatment of patellar fracture].
AB  - OBJECTIVE: To study therapeutic effects of patella and femur fixation combined
      with percutaneous suture in the treatment of patellar fractures. METHODS: In the
      study,23 patients with patellar fractures were treated with percutaneous
      Kirschner-pin transfixation and percutaneous suture after Kirschner pins
      transfixation of superior pole of patellar and condyle of femur. Among the
      patients, 17 patients were male and 6 patients were female, ranging in age from
      18 to 73 years (mean 32.4 years). The therapeutic effects were evaluated
      according to Bistman criterion for patellar fracture. RESULTS: All the patients
      were followed up and ranged from 6 to 38 months (mean 11 months). All the
      fractures were anatomically reduction or near-anatomical reduction. According to
      Bostman criterion for patellar fracture, 20 were excellent and 3 good.
      CONCLUSION: The method of patella and femur fixation combined with suture for
      patellar fractures has such advantages as smaller invasion, less complication or
      sequel, fine reduction of fracture, good restoration of joint function and none
      operative cicatrix.

PMID- 19105445
TI  - [Application of PLDD for the treatment of cervical disk herniation].

PMID- 19105446
TI  - [Chinese herbs application combined with operation for treating post-traumatic
      tibial osteomyelitis complicated with bone-skin defects].
AB  - OBJECTIVE: The aim of this study was to explore the method and clinical effects
      of integration of Chinese herbs and operation for the treatment of post-traumatic
      tibial osteomyelitis complication with bone-skin defect. METHODS: Among 28
      patients with post-traumatic tibial osteomyelitis complicated with bone-skin
      defects, 18 patients were male and 10 females, ranging in age from 18 to 68
      years, with an average of 32.5 years. All the patients were treated with
      transplantation of free iliac flaps to one-stage repair the bone-skin defects
      after infection controlled with Chinese herbs dressing. The curative effects were
      analyzed. RESULTS: All the patients were followed up and ranged from 8 to 56
      months, with an average of 30 months. All of the flap survived, and the wounds
      got primary healing in 26 patients and secondary healing in 2 patients. All the
      grafted bone united in 2 to 14 months,with a mean time of 4.6 months. The
      osteomyelitis recurred in 2 patients and got healed by focal debridement.
      CONCLUSION: Chinese herbs application combined with operation for treating post
      traumatic tibial osteomyelitis complicated with hone-skin defects is effective to
      control infection, one-stage repair the tissue defects, which is worthy
      popularizing.

PMID- 19105447
TI  - [Limited operative treatment for lumbar disc herniation and correlated analysis
      of pathological observation on nucleus pulposus].

PMID- 19105448
TI  - [Application of anchor screw in the treatment of injuries of medial collateral
      ligament of knee joint at tibial insertion].

PMID- 19105449
TI  - [Percutaneous pin fixation for the treatment of fractures of the neck of
      metacarpal bone].

PMID- 19105450
TI  - [A controlled clinical trial on the therapy of chronic osteomyelitis by perfusing
      with Corydalis saxicola bunting liquor combined with antibiotics].

PMID- 19105451
TI  - [Treatment of patella fractures with hollow screws and tension band fixation].

PMID- 19105452
TI  - [Limited internal fixation combined with external fixation for the treatment of
      pilon fractures].

PMID- 19105453
TI  - [Treatment of old acromioclavicular joint dislocation by modified Dewar method
      combined with Hook-plate].

PMID- 19105454
TI  - [Surgical treatment of cervical myelopathy by combined anterio-posterior
      approach].

PMID- 19105455
TI  - [Treatment of anterior-posterior displacement in the fracture of surgical neck of
      the humerus with over head method of manipulative reduction: a report of 168
      cases].

PMID- 19105456
TI  - [Operative treatment of bone cyst of talus through the arthroscope: a report of 1
      case].

PMID- 19105457
TI  - [Clinical application of spinal moire photography].

PMID- 19105458
TI  - [Periprosthetic osteolysis following the total hip arthroplasty].
AB  - The periprosthetic osteolysis is one of the complications of artificial joint
      replacement. The function and the stability of the hip joint will be severely
      affected once the periprosthetic osteolysis occurred postoperatively,so it's
      necessary to fully recognize the mechanism of the osteolysis. There is no
      globally accepted diagnostic standard of this disease, and then, the grading of
      the postoperative hip joint function is indispensable. The using of diphosphonate
      to prevent the osteolysis has positive significance, but it is not broadly used
      in clinical. Taking the periprosthetic osteolysis of hip arthroplasty as the
      central, this article shows a briefly overview of this subject.

PMID- 19105459
TI  - [The sural medial gastrocnemius island muscle flap to cover wound of infection on
      upper region of the tibial].
AB  - OBJECTIVE: To summarize clinical application of the sural medial gastrocnemius
      island muscle flap to cover wound of infection on upper region of the tibial.
      METHODS: Nine patients (7 men, 2 women) with soft tissue defects on the upper
      region of the tibial underwent reconstruction with the sural medial gastrocnemius
      island muscle flap. The age ranged from 21 to 60 years old (mean, 34 years). The
      immediate coverage of the muscle flaps were performed by a meshed split-thickness
      skin graft. The donor site was closed directly. The donor leg was ipsilateral in
      all cases. RESULTS: Only one case sustained superficial infection postoperative
      and the gradual wound healed by daily wound dressings. All the muscle flaps and
      skin graft had survived completely without major complication with satisfactory
      clinical results. All patients were followed-up for 13 months to 4 years (mean 21
      months), the donor site was healing, there was no remarkable donor site
      morbidity. CONCLUSION: The sural medial gastrocnemius island muscle flap is
      nourished by the medial sural artery. The muscle flaps seem to have highly
      vascularize, a constant vascular anatomy and a long vascular pedicle. The muscle
      flap is thin and suitable for repairing soft tissue defect on the upper region of
      the tibial.

PMID- 19105460
TI  - [Minimally invasive surgical treatment according to stage for open Pilon
      fracture].

PMID- 19105461
TI  - [To compare and research the clinical effect of treating the comminute distal
      radius fractures by refining splintage].
AB  - OBJECTIVE: To treat the comminute distal radius fractures by improved splint, and
      obersve the curative effect and compare the radiology with the traditional
      splint. METHODS: Ninety-two patients with distal radius comminute fracture were
      randomly divided into two groups. There were 38 males and 54 females. The average
      age was 63 years old ranging from 23 to 82. Acording to AO classification on the
      distal fracture of the radius, there were 15 cases of A3, 40 cases of C1, 26
      cases of C2 and 11 cases of C3. After all patients were treated by manipulative
      reduction, 46 cases of the treatment group were fixed supra-carpometacarpal
      joints by improved splint and trapezoid pad, the other 46 cases of control group
      were treated with the traditional spilint. Both groups were regularly taken X-ray
      recheck and changed dressings to obtain the clinical cicatrization. Patients were
      guided to do functional exercise after splints were taken off. Six weeks later
      all patients were evaluated the curative and radiologic effect according to
      Gartland-Werlley wrist score and Lidstrom grade respectively. RESULTS: According
      to wrist score,there were 13 cases on excellent, 34 cases on fine and 9 cases on
      normal in treatment group, which average score was (4.0 +/- 2.6) and the percent
      of wrist functional fitness was 80.6%. There were 9 cases on excellen, 19 cases
      on fine and 18 cases on normal in control group, which average score was (6.0 +/-
      4.2) and the percent of wrist grad and 4 cases on the third grade in treatment
      group. There were 22 cases on the first grade, 16 cases on the second grad and 8
      cases on the third grade in control group. CONCLUSION: The outcome of improved
      splint was better than that of traditional splint on the function and radiology
      for treating the comminute distal radius fracture.

PMID- 19105462
TI  - [Analysis for causes of missed diagnosis of fracture during treatment of multiple
      trauma].

PMID- 19105463
TI  - [Controlled clinical study of treatment of non-operation and surgical operation
      for scapular fracture].
AB  - OBJECTIVE: To investigate the effect of treatment methods of non-operation and
      surgical operation for scapular fracture. METHODS: A retrospective analysis of 52
      patients (male 37, female 15, ranging in age from 20 to 48 years, meanly 31
      years)with scapular fractures was done. According to Hardegger classification:
      the scapular body fracture in 24 cases, the surgical neck fracture in 12 cases,
      the anatomical neck fracture in 3 cases, the glenoidal lip fracture in 6 cases,
      the scapular spine fracrure in 7 cases. Of all 52 patients,17 cases were treated
      conservatively, and 35 were undergone surgical internal fixation. When followed
      up,the clinical examination was done and the X-ray films were taken to measure
      glenopolar angle (GPA). Hardegger function evaluation system was adopted. The
      results were analysed statiscally. RESULTS: Fifty-two cases were all followed up
      for 9 weeks to 48 months. Among 17 patients treated by non-operation, Hardegger
      function evaluation system showed that the result were excellent in 7 cases, good
      in 6, fair in 2 and poor in 2; the X-ray film results showed that there were 14
      cases of GPA > 20 degrees and 3 cases of GPA < 20 degrees. Of 35 patients treated
      by surgical operation, Hardegger function evaluation system showed that the
      result were excellent in 20 cases,good in 12 and fair in 3; the X-ray film
      results showed that there were 33 cases of GPA > 20 degrees and 2 cases of GPA <
      20 degrees. There was no significant difference between the two groups (P =
      0.27). CONCLUSION: Before treatment of scapular fracture, with CT 3D 
      recontruction, complete understanding of fragments displacement, and correction
      indication selection, and perform early exercises, both of the two procedures can
      provide satisfactory outcome.

PMID- 19105464
TI  - [Minimally invasive treatment of aged patients with intertrochanteric fracture by
      short reconstructive intrameduallary nails].

PMID- 19105465
TI  - [The location of the superficial peroneal nerve in the leg and its relation to
      the surgical approach of the fibula].
AB  - OBJECTIVE: To localize the superficial peroneal nerve in surface of the leg and
      to provide a safety surgical approach to the fibula. METHODS: Sixty-six adult
      legs preserved by 4% formaldehyde solution were studied involving 42 male and 24
      female with the average age of 69 years old ranging from 37 to 88 years. There
      were 35 cases in left and 31 in right. According to the common lateral surgical
      approach to the fibula, the superficial peroneal nerve and its branches were
      dissected in 66 embalmed leg-ankle-foot specimens. The specimens were observed
      and measured. RESULTS: The superficial peroneal nerve branched from the common
      peroneal nerve near the anterolateral aspect of the neck of the fibula,
      transversing through the muscle, deep fascia and superficial fascia. In 12 cases
      of specimens, superficial fibular nerve extended to the foot with no branches, in
      50 cases of specimens it branched out into two before piercing the deep fascia,
      in the rest 4 cases of specimens, it branched out into two before piercing the
      muscle. CONCLUSION: To avoid injuring the superficial peroneal nerve, the
      surgical approach to the 2/3 upper part of the fibula is at posterior crural
      septum, to the 1/3 lower part of the fibula is at anterior crural septum.

PMID- 19105466
TI  - [Treatment of fracture of tibia and fibula with three dimensional diaplasis
      fixation].
AB  - OBJECTIVE: To study the clinical effect of three dimensional diaplasis fixation
      in fracture of tibia and fibula. METHODS: Twenty-one cases of fracture of tibia
      and fibula were treated with three dimensions fixation (12 males, 9 females, with
      an average age of 46 years). There were 5 cases in open fracture, 16 cases in
      closed fracture, and 4 cases in up-segment fracture, 8 cases in mid-segment
      fracture, 9 cases in below-segment fracture. Oblique fracture were in 10 cases,
      thrypsis were in 8 cases, multisegmental fracture were in 3 cases. RESULTS: (1)
      Conditions of diaplasis fracture: dissected diaplasis were in 11 cases, closely
      dissected diaplasis in 9 cases, functional diaplasis in 1 case. (2) Clinical
      healing time: the minimum time was 43 days and maximum time was 85 days with an
      average of 62 days. (3) Conditions of functional recovery: all the patients were
      followed up from 4 to 12 months, 13 cases were excellent, 8 cases were good. (4)
      Time of backouting three dimensional diaplasis fixation: the minimum time was 6
      weeks and the maximum 12 weeks with an average time of 8.5 weeks. CONCLUSION: The
      three dimensional diaplasis fixation and the fracture extremity from such a three
      dimensional solid that it can satisfy crus biomechanics for treating fracture of
      tibia and fibula with unstressed barrier and uncentric stress. Moreover, the
      three dimensional diaplasis fixation is elastic, it's structure is so fixed that
      it can be favorable for bone union.

PMID- 19105467
TI  - [Effects of apolipoprotein A1 and B gene polymorphism on avascular necrosis of
      the femoral head in Chinese population].
AB  - OBJECTIVE: To investigate the effects of Apo A1 and B gene polymorphism on
      avascular necrosis of the femoral head (ANFH) in north Chinese Han population.
      METHODS: Polymerase chain reaction-restriction fragment length polymorphisms (PCR
      RFLP) technique was used in samples of 143 cases with documented ANFH and 92
      healthy control matched by age and sex individuals selected from north Chinese
      Han nationality. The studied loci include promoter region (-75bp) and the intron
      1 (+83 bp) of Apo A1 gene, Eco RI,Xba I of Apo B gene; polymerase chain reaction
      was used to study 3'-VNTR of Apo B gene. RESULTS: At -75 bp in promoter, the
      frequency of A/A genotype in ANFH group was significantly higher than that in
      control group (P < 0.01), while the frequency of G/A genotype in ANFH group was
      significantly lower than that in control group (P < 0.01). No difference was
      found in the frequency of genotype at +83bp in intron 1 of Apo A1 gene, Eco RI,
      Xba I and 3'-VNTR loci of Apo B gene. CONCLUSION: Apolipoprotein A1 gene A/A
      substitution at position -75 in promotor is associated with ANFH, the mutation
      may be one of the sensitive genes of ANFH, first reported inside and abroad. But
      no evident relationship was found between gene polymorphism of +75 bp loci of Apo
      A1 gene, Eco RI loci of Apo B gene, Xba I loci of Apo B gene or 3'-VNTR of Apo B
      gene and ANFH.

PMID- 19105468
TI  - [Revealing mechanical property of intact rabbit tibia in three-point bending
      test].
AB  - OBJECTIVE: To explore the mechanical property of intact long bone through three
      point bending test of rabbit tibia according to mechanics of materials. METHODS:
      Ten pairs of normal rabbits tibia were treated on three-point bending test with
      80 mm supporting distance in order to corroborate the virtual loading test on
      bone model. RESULTS: Bending stiffness and strength of 10 pairs of normal rabbit
      tibia were obtained. The maximum flexibility of the right and the left tibia was
      (2.737 +/- 0.262) mm and (2.739 +/- 0.233) mm respectively. The maximum load,
      which indicated the bending strength, of the right and the left tibia was (17.803
      +/- 2.675) kg and (18.366 +/- 2.653) kg respectively. The area under the load
      flexibility curve before fail of the right and the left tibia was (23.829 +/-
      4.413) kg/mm and (24.725 +/- 4.101) kg x mm respectively. The slope of the load
      flexibility curve which indicate the stiffness of the right and the left tibia
      was (7.545 +/- 1.310) kg/mm and (7.631 +/- 1.174) kg x mm respectively.
      CONCLUSION: The discrepancy between different animal body is larger than
      conventionally required. It's suggested for performing three-point bending test
      of long bone of the body both sides in pair.

PMID- 19105469
TI  - [Research on safe implantation of upper-middle thoracic pedicle screws under the
      X-ray perspective].
AB  - OBJECTIVE: To explore the method of implanting upper-middle thoracic pedicle
      screws under monitoring by X-ray and evaluate accuracy and safety. METHODS: (1)
      Six normal adult thoracic spine samples (T1-T8) were selected, from which single
      spine units were separated. A surgical probe went in along the pedicle axis. By C
      shaped arm X-ray, the four probe positions were recorded: at the entering point,
      the front end of the probe in the middle of the pedicle, at the pack of the
      spine, and under the cortex of the front of the spine. The position of the front
      end of the probe at the entering point, and the front end of the probe at
      different depth at central-side perspective position were analyzed. The related
      positions and their corresponding changing rules were also analyzed. (2) Based on
      the changing rules mentioned above, different steps were adopted under the
      guidance of the C-shaped arm X-ray, to safely implant upper-middle thoracic
      pedicle screws. First, six T1-T8 spine samples were used, and under the guidance
      of the C-shaped arm device, 96 pedicle screws were implanted. After the
      operation,the sping samples were scanned through CT, and the positions of the
      screws were determined. RESULTS: According to the result of the CT scanning, the
      result were excellent (the screw was safely inside the pedicle) in 90 screws;
      Medium (the screw penetrated a little of the inside or outside bone cortex,
      within 2 mm) in 6; No one was had (the screw penetrated a lot, more than 2 mm).
      CONCLUSION: The implantation of upper-middle thoracic pedicle screw under the
      guidance of the C-shaped arm X-ray perspective is a simple and feasible method,
      and improve the accuracy and safety.

PMID- 19105470
TI  - [Treatment for crush syndrome of extremities with antioxidants].
AB  - OBJECTIVE: To study the clinical therapeutic effect of antioxidants assistant
      treatment of extremities crush syndrome (CS)in order to find new therapy.
      METHODS: Twenty-one male patients (aged from 24 to 48 years, mean 36 years) were
      treated with the next antioxidants in early stage: (1) 20% Mannitol 250 ml
      intravenous drip in 30 minutes (one time per 6 to 8 h). (2) Sodium aescinate 20
      mg, Salvia Miltiorrhiza 20 ml were dissolved respectively in isotonic saline or
      5% glucose 200 ml and dripped by intravenous drip (50 to 60 drips per minute).
      The drugs were used for 5 to 7 days (one time per day). Basifying urine, keeping
      the nagative liquid banlance and electrolyte banlance, preventing infection and
      hold out treatment were done. When the pressure of muscular osteofascial
      compartment was more than 30 mmHg, deep fasia was cut to decompress timely and
      the above-mentioned drugs were continuously applied for patients. RESULTS:
      Myoglobin urine of 21 cases died out after 2 to 3 days, of them, 13 cases were
      performed to decompress. After open decompression, 2 cases suffered from
      amputation because of long time of ischemia, 2 cases took place slight
      dysfunction of lower limbs, one hand had ischemia muscular contracture in 1 case
      and one foot down-vertical in 1 case. After followed-up of 8 months to 1 year,
      according to the function standard, the result were excellent in 8 cases, good in
      7 cases, fair in 2 cases, poor in 4 cases. The excellent and good rate was about
      71.4% (15/21). CONCLUSION: After extremities crushed for long time, application
      of antioxidents as early as possible can decrease significantly the incidence and
      invalidity rate of CS.

PMID- 19105471
TI  - [Treatment of refracture in plate-screw fixation of femoral shaft with plate and
      xenogenic bony plate].
AB  - OBJECTIVE: To evaluate curative effect of plate and xenogenic bony plate were
      applied in refracture in plate-screw fixation of femoral shaft. METHODS: Thirteen
      cases of refracture in plate-screw fixation of femoral shaft included 8 males and
      5 females, average age was 31.2 years ranging from 14 to 57. Fracture type was
      comminuted fracture in 7 cases, oblique fracture in 4 cases, transverse fracture
      in 2 cases. Fixation type used eight holes femoral LC-DCP in 5 cases, eight holes
      epipodite LC-DCP in 2 cases, six holes femoral LC-DCP in 2 cases, 8 holes La
      Plate in 4 cases. All the patients were treated by femoral LC-DCP and xenogenic
      bony plate. RESULTS: All of the patients were followed up from 16 to 40 months
      with average of 32 months. All cases had undergone only one operation and
      achieved bony union. Average time of bony union was 9 months. The lower limbs
      resumed walk and beared a heavy burden. According to criterion of Merchan, the
      results were excellent in 7 cases,good in 4,fair in 1 and poor in 1, the
      excellent and good rate of knee function was 84.6% (11/13) in one year after
      operation. CONCLUSION: Treatment of refracture in plate-screw fixation of femoral
      shaft with armor plate and xenogenic bony plate is a reliable treatment.

PMID- 19105472
TI  - [Treatment of humeral supracondylar fracture through small lateral incision].
AB  - OBJECTIVE: To explore the effect of treatment of humeral supracondylar fracture
      with Kirschner and tension band wire fixation through small lateral incision.
      METHODS: Fifty-eight patients of humeral supracondylar fractures included 42
      males and 16 females with the average age of 9.4 years ranging from 3 to 65 years
      old. All patients were treated with Kirschner and tension band fixation through
      small lateral incision of 4 to 5 cm after reduction through lateral approach from
      the inter muscular space between the lateral of triceps brachii and the
      brachioradial muscle. Two Kirschner were insterted from the lateral condylars to
      humeral medial. Drill plumb on the humeral above fracture line distance 2 to 3
      cm. A wire through bended on the lateral two Kirschners nails crossed in the
      shape of "8" figure. RESULTS: The fracture obtained accurately reduction and
      rigidly fixation. All patients were followed up for 1 to 5 years (mean 2.4
      years). According to Flynn clinical evaluation, the results were excellent in 48
      cases, good in 6,fair in 3 and poor in 1. CONCLUSION: This method has advantages
      of minimal trauma, easy manipulation, less operative time, early exercises and
      rapid recovery for the treatment of humeral supracondylar fracture.

PMID- 19105473
TI  - [Treatment of proximal interphalangeal fracture with palmar plaster external
      fixation].

PMID- 19105474
TI  - [Taking ilium inner table to repair the articular surface defects of complex
      fracture of tibial plateau].
AB  - OBJECTIVE: To study the feasibility of application of ilium inner table to repair
      the articular surface defects of tibial plateau complex fractures. METHODS:
      Twenty-three patients with tibial plateau complex fractures included 17 males and
      6 females with an average age of 28.3 years old ranging from 18 to 51 years. The
      area of the articular surface defects ranged from 1 cmx2 cm to 3 cmx3 cm,
      averaged 6.7 cm2. Taking ilium inner table with periosteum after trimmed and
      implanting into the articular surface defect area with the concavity upward and
      drilled with diameter 1.5 mm Kirschner pin interval 3 to 4 mm. Bone grafting were
      placed under the ilium inner table and were fixed by T-shaped or L-shaped plate.
      The wounded limb were braked by plaster for 4 weeks after operation. RESULTS:
      Twenty-three patients were followed-up for 8 months to 3 years, averaged 13.6
      months. X-ray film showed solid union and the smooth articular surface in all
      cases. According to the Rasmussen evaluation system, the results were excellent
      in 11 cases, good in 8 cases,fair in 3 cases, poor in 1 case. CONCLUSION: Taking
      ilium inner table to repair the articular surface defects of tibial plateau
      complex fractures is a good resolving measures. It can repaire major area of
      articular surface defects, restore the smooth articular surface and acquire good
      function of knee joint with easy to operate, less complications at donor area.

PMID- 19105475
TI  - [Treatment of tibial fracture with interlocking intramedullary nail and tripus].
AB  - OBJECTIVE: To explore the method and effect of inter-locking intramedullary nail
      and tripus in closed reduction for treating tibial fracture. METHODS: One hundred
      and twenty-six patients of tibial fractures were treated by inter-locking
      intramedullary nail and tripus in closed reduction. There were 76 males and 50
      females aged from 25 to 68, the mean age was 38; There were 86 close fractures
      and 40 open fractures (Gustilo I and II type). AO classification system was used
      for all cases, fracture type A in 49 cases, type B in 41 cases, type C in 36
      cases. RESULTS: All patients were followed up for 10 to 16 months. Fratures were
      cured, according to the criteria of Johner-Wruhs, the results were excellent in
      103 cases, good in 18 cases, fair in 5 cases. CONCLUSION: Inter-locking
      intramedullary nail is the optimal operation method in treating tibial fracture.
      Static locking should be a routine way, and closed reduction, no stripping
      periosteum, infectious rate and complications are reduced. Through tripus work
      intensity are reduced and reduction easily during operation.

PMID- 19105476
TI  - [Treatment of lumbar disc herniation with lateral recess stenosis by
      microendoscopic discectomy].

PMID- 19105477
TI  - [Treatment of floating knee injury].
AB  - OBJECTIVE: To explore the clinical outcome of floating knee injury treated by
      open reduction and internal fixation. METHODS: The course of treatment of
      floating knee in 78 cases by open reduction and internal fixation were reviewed.
      There were 59 males and 19 females, aged from 17 to 58 years old, with an average
      age of 37.5 years. Intramedullary nail, pressure plate hollow screw, multi
      function single side external fixation holder and other internal fixature were
      used in the operation. Early exercises were followed postoperatively. RESULTS:
      All patients were followed-up for 8 to 35 months (mean 18.6 months). According to
      the criterion of Karlstrom, of the 48 cases with femoral shaft fracture, 45 were
      excellent and 3 were good. In the 11 cases of bimalleolar fracture, 5 were
      excellent, 3 good, 1 fair and 2 bad. Of the 19 cases of mixed fracture, 9 were
      excellent,6 good, 3 fair and 1 bad. CONCLUSION: Strict sterilization, non
      invasion and standard internal and external fixation could make the fracture
      anatomical reduction and firm fixation. It is beneficial to early rehabilitation
      exercise. Complications such as malunion, and stiff joint could be avoided. The
      clinical outcome were satisfactory.

PMID- 19105478
TI  - [Causes and countermeasure of complications in operative management of intra -
      articular fracture of calcaneus].
AB  - OBJECTIVE: To discuss the probable causes of the post-surgery complications with
      the intra-artcular fracture of calcaneus, the proper steps for prevention and
      solution. METHODS: Seventy-one patients (76 injured feet) included 49 males and
      22 females aged from 19 to 56 years old (mean 35.6 years). According to Sanders'
      classification, 23 cases (24 injuried feet) belonged to type II, 36 (38 injured
      feet) were type III, the remain 12 (14 injured feet) met the criteria of type IV.
      All the patients received the operation of open reduction, autogenous bone
      grafting and internal fixation with stainless steel plates. RESULTS: Thirteen
      injuried feet developed early complications. Two injuried feet got the
      superficial layer of the wound disrupted and infected, I had the deep layer of
      the wound disrupted and infected. Cutaneous necrosis at the pointed end of the
      wound occurred in 7 cases. Another 1 developed osteomyelitis. Two cases suffered
      from sural nerve damage. Two injuried feet developed late complications, both of
      them suffered from arthritis of talocalcaneal joint. All the patients were
      followed up at least 6 months (ranged from 6 to 42 months, mean 19 months).
      According to Kerr's post-surgery evaluation criteria, 34 injuried feet were
      excellent, 32 were fine, 9 were acceptable, only 1 was bad. CONCLUSION: If proper
      measures are taken, the post-surgery complications of intra-articular fracture of
      calcaneus will be reduced. This requires us to be strict in selecting operation
      indication, to make a good plan and preparation, to select a right time for
      operation, to improve surgical skills and pay more attention to peri-surgery
      nursing. If complications happen, according measures should be taken in order to
      get a better outcome.

PMID- 19105479
TI  - [Treatment of fractures of the talar neck with hollow compression screw via inner
      malleolus approach].
AB  - OBJECTIVE: To explore clinical effect of treatment of fractures of the talar neck
      with hollow compression screw via inner malleolus tomy approach. METHODS: Twelve
      patients with fractures of the talar neck included 7 males and 5 females with a
      mean age of 38 years (reaging from 20 to 56 years). According to the Hawkins
      classification, 8 cases were type II and 4 cases were type II. Twelve patients
      were treated with hollow compression screw via inner malleolustomy approach.
      RESULTS: All the patients were followed up for 1 year to 6 years and 8 months
      (average 4 years and 5 months), all the fractures were bony union. The mean
      Hawkins score was excellent in 5 cases, good in 5 cases, fair in 1 case and poor
      in 1 case. CONCLUSION: It is a good method to treat the fractures of the talar
      neck with hollow compression screw via inner malleolus tomy approach.

PMID- 19105480
TI  - [Surgical treatment of the sacrum tumor].
AB  - OBJECTIVE: To discuss the surgical methods and effects in the treatment of sacrum
      tumor. METHODS: Fifteen patients of sacrum tumor included 12 males 3 females aged
      from 17 to 68 years old,mean 54.6 years. Ten cases were primary tumor and 5 were
      metastatic tumor. Five cases underwent anterior approach tumor extirpation, 3
      posterior approach tumor extirpation and 7 posterior tumor extirpation with bone
      graft and internal fixation of a pedicle screw and rod system. Additionally, all
      cases were treated with radiotherapy or/and chemotherapy post-operatively
      according to the character of the tumor. RESULTS: Thirteen patients were followed
      up for 4 months to 5 years. One patient had exacerbation accompanying dysfunction
      of urinary and feca after surgery, which relieved after four months of non
      operative treatments. One chordoblastoma and 2 metastatic tumor died of
      recurrence and metastasis 1 to 2 years after operation, respectively. And in
      another case of giant cell tumor occurred the local recurrence 6 months after
      operation, who refused secondary surgical treatment. CONCLUSION: Individualized
      surgical treatment with conbination of radio therapy or/and chemotherapy will
      make good results for patients with sacrum tumor.

PMID- 19105481
TI  - [Operative treatment of lumbar spinal canal stenosis with lumbar instability].

PMID- 19105482
TI  - [Treatment by limited-incision for posterior edge separation of lumbar vertebral
      body].
AB  - OBJECTIVE: To discuss effective operative method for posterior edge separation of
      lumbar vertebral body. METHODS: Twelve cases of posterior edge separation of
      lumbar vertebral body were categorized as lateral type and central type, and were
      operated upon with limited-incision using lamina retractor. All patients were
      male and with an average age of 30 years (range, 23 to 40 years). The average
      history of disease was 17.9 months. In lateral type cases, separation bone was in
      the posterolateral lower edge of L4 vertebral body in 1 case, in the
      posterolateral upper edge of L5 vertebral body in 3 cases and in the
      posterolateral upper border of S1 vertebral body in 6 cases, all with ipsilateral
      disc herniation. Lateral type cases were treated with unilateral fenestration and
      removal of disc nucleus and posterior bony edge. Separation bone was in the
      central upper edge of S1 vertebral body with central disc herniation in 2 central
      type cases. Two central type cases were treated with bilateral fenestration and
      removal of disc nucleus and posterior bony edge. RESULTS: All patients were
      followed up for 12 to 36 months, and the average follow-up was 22.5 months.
      According to Macnab postoperative evaluation criterion, the results were
      excellent in 10 cases, good in 2 cases. CONCLUSION: Limited-incision for
      posterior edge separation of lumbar vertebral body has characteristic of less
      trauma and convenience. It is an effective method for removal posterior bony
      edge.

PMID- 19105483
TI  - [Surgical operation combined with traditional Chinese medicine for treating
      tuberculosis of ankle joint in 56 cases].

PMID- 19105485
TI  - [Treatment of old type III acromioclaricular joint dislocation with tension band
      and coracoclavicular ligament reconstruction].

PMID- 19105484
TI  - [Treatment of atlantoaxial instability with C1-C2 posterior transarticular screw
      fixation].
AB  - OBJECTIVE: To evaluate the technique of C1-C2 transarticular screw fixation for
      atlantoaxial instability or dislocation. METHODS: Among 14 patients with
      atlantoaxial instability, 10 were male and 4 patients were female, with an
      average age of 38.6 years ranging from 17 to 62 years. All patients were treated
      by internal fixation with transarticular screws. RESULTS: There were 28 screws
      applied in 14 patients. All patients were followed up. The average follow-up
      period was 16 months (range, 9 to 35 months). The postoperative JOA score was
      ranging from 13.8 to 15.8 with the average score of (14.50 +/- 0.66) and the
      improved rate of (76.12 +/- 4.94)%. No spinal injury and vertical artery injury
      was found and osseous fusion was completed in all patients. CONCLUSION: The
      technique of C1-C2 transarticular screw fixation is one of the best treatments
      for atlantoaxial instability. Without the help of structural bone graft and aided
      internal fixation, morselized cancellous bone graft can acquire effective osseous
      fusion.

PMID- 19105486
TI  - [Clinical application of endoscopic two-portal one-way releasing procedure for
      carpal tunnel syndrome].
AB  - OBJECTIVE: To study the method and effect of endoscopic two-portal one-way
      releasing procedure for cut of transverse carpal ligament and decompression of
      median nerve. METHODS: Eleven female patients (13 sides) with primary carpal
      tunnel synrome underwent endoscopic two-portal one-way releasing procedure, there
      were 3 left hands, 6 right, and 2 both. All the subjects had hypesthesia in the
      radial three and half finger's tip with a positive, Tinel sign of median nerve at
      wrist; 11 cases had thenar myatrophy in which 4 had opposition dysfunction. Under
      local anaesthesia, the proximal incision was located at the point of the proximal
      carpal transverse striation level between palmaris longus and flexor carpi
      radialis. The outlet was chosed the junction of the parallel line of the ulnar
      side of thumb and proximal extending line of middle ring fingers' long axis while
      the thumb was in abduction position. The length of each incision was only one
      centimeter. The hook knife was inserted to the proximate of the transverse carpal
      ligament, then, the transverse carpal ligament was completely released form the
      proximal to the distal end by hook knife under the endoscope monitor. RESULTS:
      The results showed that both pinch and grip function was satisfied and no
      complications occurred at 4 to 20 months followed-up. S3+ M3 or more has been
      reached in 3 months after operation. CONCLUSION: The endoscopic two-portal one
      way releasing procedure is an easy and effective method for the treatment of
      carpal tunnel syndrome.

PMID- 19105487
TI  - [Steel plate internal fixation for the treatment of high-energy Pilon fractures].

PMID- 19105488
TI  - [Middle-long-term postoperative clinical observation of therapeutic effect of
      disc excision in adolescent LIDH].

PMID- 19105489
TI  - [Treatment of calcaneal fractures with closed prying and internal fixation with
      round pin compound with manipulative reduction].

PMID- 19105490
TI  - [Comparison between arthroscopic and open retrograde interlocking intramedullary
      nail in the treatment of distal femoral fractures].

PMID- 19105491
TI  - [Treatment of complicated tibial shaft fracture with less invasive stabilization
      system].

PMID- 19105492
TI  - [Analysis of diagnosis and treatment for juvenile ankylosing spondylitis in 5
      cases].

PMID- 19105493
TI  - [Closed reduction and percutaneous internal fixation for the treatment of finger
      fractures].

PMID- 19105494
TI  - [Kirschner and tension band fixation for the treatment of avulsion fracture at
      the apex of patella: a report of 138 cases].

PMID- 19105495
TI  - [Total hip joint replacement for the reconstitution of cotyla in treating hip
      arthodysplasia].

PMID- 19105496
TI  - [Pelvic fractures combined with female genital organ injury].

PMID- 19105497
TI  - [Manipulative reduction of the posterior dislocation of the elbow by one person].

PMID- 19105498
TI  - [Manipulative reduction for the treatment of clavicular fracture].

PMID- 19105499
TI  - [Causes of delayed diagnosis of multiple trauma in emergency patients].

PMID- 19105500
TI  - [Study on the progress of the mechanism of TGF-beta in the scarring and the
      effect of TCM].
AB  - Transforming growth factor (TGF-beta) plays a central role in wound healing and
      scarring. TGF-beta is a member of cytokine family, involving cell proliferation,
      migration, differentiation and apoptosis, which subsequently trigger
      extracellular matrix (ECM) deposite and collagen overproduction. A number of
      regulators of TGF-beta expression bave been identified, including Decorin CTGF,
      etc. TCM can reduced later scarring, and it accelerates wound healing. TCM can
      reduce the expression of TGF-beta, resistance of fibrosis, so that lighten the
      development of scar. This article reviewed the mechanism of TGF-beta in the
      scarring and TCM can decrease the development of scar effected by TGF-beta.

PMID- 19105501
TI  - [Advancement in drug therapy of spinal cord injury].
AB  - With the increasing progress to know spinal cord injury (SCI) in experimental and
      clinical study and the confirming clinical effect to treat SCI with early
      methylprednisolone in ninety decade of 20th century, the mechanism of
      methylprednisolone therapy is understood continuously. Based on them above, a lot
      of new drugs are found effective for SCI. We want to give a review about it.

PMID- 19105502
TI  - Prophylaxis in congenital coagulation disorders: past, present and future.

PMID- 19105503
TI  - Primary prophylaxis in children with haemophilia.
AB  - Starting from the clinical observations that moderate haemophiliacs experienced
      only few bleeding episodes and rarely developed significant joint deterioration
      (haemophilic arthropathy), and the pioneer experience in Sweden, prophylaxis
      (i.e. the regular and long-term administration of clotting factor concentrate in
      order to prevent bleeding) has been practiced for more than forty years in severe
      haemophilia and is currently recommended as the first choice of treatment by the
      World Health Organisation and World Federation of Hemophilia and by many national
      medical/scientific organizations. Observational studies clearly established the
      superiority of prophylaxis over on-demand treatment in reducing the risk of
      arthropathy, also showing that starting prophylaxis earlier in life and after
      very few joint bleeds was associated with better joint outcomes, and led to the
      current definitions of primary (started before the age of 2 yrs and after no more
      than one joint bleed) and secondary prophylaxis. More recently, evidences from
      randomized trials, which were previously lacking in this setting, were also
      provided. This review summarizes available data from which current clinical
      practice of primary (and early secondary) prophylaxis in children with severe
      haemophilia was drawn. Open issues concerning optimal regimens and barriers to
      the implementation of prophylaxis are also discussed.

PMID- 19105504
TI  - Barriers to primary prophylaxis in haemophilic children: the issue of the venous
      access.
AB  - Modem treatment for hemophilic children is based on prophylaxis and immune
      tolerance induction (ITI). Both treatment regimens are based on frequent
      infusions at early ages, therefore an adequate venous access is essential.
      Peripheral veins represent the best option, however, different solutions, as
      central venous access devices (CVADs) and arteriovenous fistulae (AVFs), can be
      adopted if needed. CVADs have been used in hemophiliacs, however their survival
      is affected by infectious complications. Among CVADs, fully implantable devices
      are usually preferred to external lines due to a lower infectious risk. The
      limited survival of CVADs may have a relevant impact on treatment outcome,
      especially in case of ITI where treatment interruptions are counterproductive. To
      overcome such drawbacks, internal AVF has been considered as an alternative
      option owing to a lower rate of infectious complications. Moreover, AVF is easy
      to use in the home setting and well accepted by children. Possible complications
      not preventing AVF use are postoperative hematoma and transient symptoms of
      distal ischemia; one case of symptomatic thrombosis has been reported so far.
      Long-term complications include loss of patency, aneurysmatic dilatation and,
      rarely, limb dysmetria and a regular follow-up is mandatory to allow early
      remedial intervention. Surgical dismantlement of AVF is recommended as soon as
      transition to peripheral veins is possible.

PMID- 19105505
TI  - Secondary prophylaxis in adolescent and adult haemophiliacs.
AB  - Progressive arthropathy of large joints of the limbs (knees, ankles, elbows),
      resulting from recurrent joint bleeds and subsequent long-term degenerative
      phenomena, is one of the main causes of morbidity and of deterioration of quality
      of life in adult severe hemophiliacs. While primary prophylaxis (i.e. the regular
      continuous long-term infusion of factor concentrates started before the age of
      two years and/or after no more than one joint bleed) is nowadays considered the
      gold standard for preserving joint function in patients with severe haemophilia,
      the benefits of secondary prophylaxis (i.e., all the long-term regular treatments
      not fulfilling the criteria of primary prophylaxis) are still controversial. In
      this review we present the literature data on secondary prophylaxis, focusing on
      adolescent and adults haemophiliacs along with clinical experience in Italy. On
      the whole, the more recently published studies suggest the effectiveness of early
      and delayed secondary prophylaxis. However, a number of questions are still
      unanswered, including the optimal dose, dosing interval and duration of secondary
      prophylaxis. Only large, prospective, long-term, possibly randomized studies will
      help to definitively assess the clinical impact of this strategy in adolescent
      and adult hemophiliacs.

PMID- 19105506
TI  - Secondary prophylaxis with factor IX concentrates: continuous infusion.
AB  - Haemophilia patients may require prolonged treatment during peri-operative period
      or life-threatening bleedings. Intermittent bolus infusions of factor
      concentrates have been used successfully for many years. However,
      pharmacokinetics may vary among products and patients, and the wide fluctuations
      in factor levels during therapy can make management inaccurate and unsafe.
      Specific protocols for continuous infusion have been developed, which may
      decrease factor utilization, facilitate laboratory monitoring of factor levels,
      and may decrease the overall cost of therapy. Continuous infusion of different
      clotting factor concentrates (factor VIII, factor IX, porcine factor VIII,
      rFVIIa, and activated prothrombin complex concentrates) has been associated with
      excellent haemostasis and safety: indeed, by continuous infusion unsafe low
      troughs or dangerous high concentrations can be avoided. In this review, the
      pharmacokinetic aspects of the continuous infusion of plasma-derived and
      recombinant factor IX concentrates are showed. Finally, the advantages and
      disadvantages of continuous infusion are discussed.

PMID- 19105507
TI  - Prophylaxis of bleeding episodes in patients with von Willebrand's disease.
AB  - Patients with severe forms of von Willebrand's disease (VWD) may have frequent
      haemarthroses, especially when factor VIII (FVIII) levels are below 10 U/dL, so
      that some of them develop target joints like patients with severe haemophilia A.
      Some patients have recurrent gastrointestinal bleeding, often without lesions in
      the gastrointestinal tract, and need treatment every day or every other day.
      Finally, there are children who have epistaxis frequently and severely enough to
      cause anaemia. In these frequent and severe bleeders, the optimal therapy may be
      secondary long-term prophylaxis with von Willebrand factor (VWF)/FVIII
      concentrates rather than on-demand treatment on the occasion of bleeding
      episodes. The largest experience on such prophylaxis in VWD has been in Sweden in
      35 patients with severe forms of VWD. Long-term prophylaxis was also implemented
      in a cohort of Italian patients with VWD: prophylaxis was used in seven patients
      with types 3 (n = 1 ), 2A (n = 4), 2M (n = 1) and type 1 (n = 1) VWD because of
      recurrent gastrointestinal bleeds and in four patients with type 3 VWD because of
      joint bleeds. Prophylaxis prevented bleeding completely in eight patients and
      largely reduced hospitalisation for blood transfusions in the remaining three.
      The cost-effectiveness of these prophylaxis regimens versus on-demand therapy
      will now be investigated in one large international study

PMID- 19105508
TI  - Surgical prophylaxis in von Willebrand's disease: a difficult balance to manage.
AB  - Von Willebrand disease (VWD) is the most common genetic bleeding disorder with a
      prevalence of approximately 1-2 percent confirmed in different population
      studies. The severity of the bleeding tendency is usually proportional to the
      degree of the VWF defect, although the large majority of cases diagnosed appear
      to have a mild disease. Patients with VWD may require short- or long-term
      prophylaxis treatment. Short-term prophylaxis is usually performed to prevent
      excessive bleeding following surgery or invasive procedures, while long-term
      prophylaxis may be needed to control recurrent mucosal and joint bleeding
      complicating the more severe forms of VWD. This review is focused on the current
      knowledge on replacement treatment for patients with VWD disease undergoing
      surgical or invasive procedures. On the whole, the published studies document the
      safety and efficacy of VWF/FVIII concentrates as surgical prophylaxis in VWD
      patients, in particular of Haemate P, the most widely used VWF/FVIII concentrate
      due to its high VWF:FVIII ratio. The recent literature data also show that the
      best management of VWD patients undergoing surgery is that to perform a
      pharmacokinetic study in order to strictly tailor for each VWD patient loading
      and maintenance doses of VWF/FVIII concentrates. Furthermore, the same studies
      underscore that, along with VWF levels, FVIII levels should be monitored in the
      peri-operative period in order to prevent exposures to high FVII levels,
      associated with an increased risk of venous thrombosis.

PMID- 19105509
TI  - Prophylaxis of bleeding episodes and surgical interventions in patients with rare
      inherited coagulation disorders.
AB  - Rare inherited coagulation disorders (RICD) represent a group of inherited
      deficiencies of clotting factors characterized by a low prevalence in the general
      population (usually around 1:1,000,000 inhabitants) and, in severe cases
      (homozygous or compound heterozygotes), by the invariable occurrence of bleeding
      after invasive procedures if not adequately treated. Furthermore, spontaneous or
      post-traumatic severe bleeding may occur, as usually observed in patients with
      haemophilia, although less frequently. The clinical picture of patients with RICD
      may, however, be complicated by particular situations not encountered in
      haemophiliacs, such as gynaecological bleeding. The availability of virally
      inactivated plasma-derived concentrates of the missing factors, apart from factor
      V, has rendered surgery and prophylaxis more feasible in these disorders, thus
      reducing the risk of life-threatening episodes and significantly improving the
      quality of life of affected patients. The goal for the future is to render this
      treatment accessible to all patients with these disorders, also to those living
      in developing countries.

PMID- 19105510
TI  - The wisdom of complexity.

PMID- 19105511
TI  - Case study: an ethical dilemma involving a dying patient.
AB  - Nursing often deals with ethical dilemmas in the clinical arena. A case study
      demonstrates an ethical dilemma faced by healthcare providers who care for and
      treat Jehovah's Witnesses who are placed in a critical situation due to medical
      life-threatening situations. A 20-year-old, pregnant, Black Hispanic female
      presented to the Emergency Department (ED) in critical condition following a
      single-vehicle car accident. She exhibited signs and symptoms of internal
      bleeding and was advised to have a blood transfusion and emergency surgery in an
      attempt to save her and the fetus. She refused to accept blood or blood products
      and rejected the surgery as well. Her refusal was based on a fear of blood
      transfusion due to her belief in Bible scripture. The ethical dilemma presented
      is whether to respect the patient's autonomy and compromise standards of care or
      ignore the patient's wishes in an attempt to save her life. This paper presents
      the clinical case, identifies the ethical dilemma, and discusses virtue ethical
      theory and principles that apply to this situation.

PMID- 19105512
TI  - Creating an aging-prepared community in the inner city: an early descriptive
      evaluation.
AB  - As the population ages, and healthcare costs continue to rise, innovative models
      to address these twin issues of cost-effective elder care continue to evolve.
      Looking to the community as the context for care requires new ways of thinking
      about how to develop and evaluate services. This paper describes the Neighborhood
      Health Advocate Program (NHAP), an innovative approach to supporting inner-city
      minority older adults to live in their homes, as well as testing a model for
      program evaluation based on an action research approach.

PMID- 19105513
TI  - Do physician practice patterns and business structure hurt quality care in
      outpatient dialysis?

PMID- 19105514
TI  - Medicare to stop paying hospitals for medical errors.

PMID- 19105515
TI  - Believing in the buttonhole technique.
AB  - Vascular access cannulation for dialysis staff is the most difficult obstacle to
      overcome during the orientation process and can remain a challenge throughout
      one's career in caring for patients with renal disease. Learning the "buttonhole
      technique" can make venipuncture more comfortable for the patient and can
      eliminate the fear of failure for the cannulator. Not only does it preserve the
      timeframe of the patient's access, but establishes a routine process for the
      dialysis facility to follow for successful cannulation.

PMID- 19105516
TI  - The Missouri Kidney Program's Patient Education Program: a 12-year retrospective
      analysis.
AB  - Unbiased patient education for individuals with chronic kidney disease can result
      in a multitude of positive benefits. The current study reviewed 1,844
      participants in a six-topic patient education program over a 12-year period from
      June 1994 to July 2006, examining patients' level of knowledge about CKD,
      preferences for treatment, and feelings of hope and fear before and after the
      educational intervention. After the educational intervention, patients scored
      significantly higher on knowledge tests of all topics than they scored on the pre
      test (p < .05). Overall, there were no significant differences from pre- to post
      test on self-ratings of being "scared" or "hopeful," although on the post-test,
      females were significantly more hopeful than males (p < .01). More patients were
      interested in peritoneal dialysis as a treatment option after class attendance (p
      < .001). Multivariate logistic regressions indicated that patients who were
      older, black, or who had a high school education or less were more likely to
      prefer center hemodialysis (p < .007). Although overall interest in the
      transplant option did not change significantly from pre- to post-test, younger
      patients (52 vs. 67 mean years, p < .001) and males (59% vs. 54%, p = .02) were
      more interested in receiving a transplant.

PMID- 19105517
TI  - Going home, again: Congress and CMS remove major disincentives to home dialysis.

PMID- 19105518
TI  - Advance directives and an important supplement--physician orders about life
      sustaining treatments.

PMID- 19105519
TI  - Rethinking Maslow and patient adherence.

PMID- 19105520
TI  - Loud and clear.

PMID- 19105521
TI  - Seeking refuge with HIV/AIDS.

PMID- 19105522
TI  - A key worker.

PMID- 19105523
TI  - Weighty responsibility?

PMID- 19105524
TI  - Sharing evidence: community practitioners writing for publication.
AB  - This paper aims to inform and encourage community practitioners to contribute to
      the evidence available to their colleagues, in order to develop practice,
      education, policy and research. It begins by discussing the main reasons for
      publication, as well as outlining some of the commonly-held myths and realities
      of the publication process. Key steps to publication are considered, including
      deciding on a topic and focus, assessing the material and targeting the right
      journal. Many community-based professionals are increasingly interested in
      writing for publication, and 'Community Practitioner' provides an ideal channel
      through which to disseminate evidence for community practice. This paper outlines
      the many different forms in which authors may write for publication in this
      journal, including opinon pieces and clinical updates, as well as more in-depth
      and lengthy professional papers.

PMID- 19105525
TI  - Inequalities in child health up to five years: a supradistrict audit.
AB  - Reducing inequalities is a key national priority. This paper describes a unique
      retrospective multidisciplinary audit that was carried out across the Greater
      Manchester area. The aim of the audit was to identify the extent to which local
      health and local authority services were implementing evidence-based
      interventions to reduce health inequalities in children aged below five, using
      both qualitative and quantitative approaches. Health visitor and midwifery
      records were audited against service provision around seven standards--reducing
      postnatal depression, promoting breastfeeding, social and emotional support for
      parents, improving the health of looked-after children, improving nutrition in
      children and women of childbearing age, provision of day care and pre-school
      education, and reducing smoking in pregnancy and the postnatal period. The
      results suggest that recommendations for reducing inequalities were not
      implemented across all geographic areas, services or populations consistently,
      particularly in relation to smoking cessation, the management of postnatal
      depression and the promotion of breastfeeding initiation and continuation. It is
      recommended that, with the widening gap in health outcomes between both ends of
      the socioeconomic spectrum, local services should be targeted for those most in
      need.

PMID- 19105526
TI  - Smoke-free homes: outcomes of a local service development.
AB  - This paper aims to determine the impact of a smoke-free homes initiative in
      Doncaster. An evaluation was conducted via a self-reported semi-structured
      questionnaire and telephone survey in 2006. Numbers and types of smoke-free homes
      promises, self-reported smoking restrictions in the home and factors associated
      with smoke-free homes were measured. A total of 825 smoke-free home promises were
      received, of which 567 (69%) were 'gold', 221 (27%) 'silver' and 37 (4%)
      'bronze'. Of these promises, 523 (63%) were from smokers. Non-smokers (95%) and
      smokers who had just stopped (91%) were more likely to opt in for a gold promise
      when compared to smokers (52%, p<0.001). Over half of smokers who opted for the
      gold promise reported not allowing smoking in the house (57%, p<0.001). Of 82
      responses at follow up, 41 (50%) reported smoking outside the house or in the
      street. Engaging families in the implementation of smoke-free homes is an
      effective measure to reduce household second-hand smoke exposure. Further
      research is required to assess the long-term feasibility, sustainability and cost
      per quitter.

PMID- 19105527
TI  - A service at crisis point.

PMID- 19105528
TI  - Teaching and learning.

PMID- 19105529
TI  - Addressing problems at work.

PMID- 19105530
TI  - Breast cancer and ovarian cancer genetics: an update.
AB  - The purpose of this report on breast cancer and ovarian cancer genetics is to
      review the evidence for the efficacy of surveillance for early detection,
      bilateral prophylactic mastectomy, prophylactic oophorectomy, and chemoprevention
      in preventing breast cancer and improving survival of BRCA1 and BRCA2 carriers.
      This collective review highlights radiologic screening of patients with this
      genetic predisposition for cancer as well as discusses cancer risk reduction
      strategies and reproductive concerns in female BRCA1/2 mutation carriers. It has
      now been well documented that magnetic resonance imaging (MRI) of the breast has
      a higher sensitivity than mammography for the diagnosis of breast cancer in
      patients predisposed to breast cancer. We also emphasize that a new diagnostic
      device, molecular breast imaging (MBI), is now available and may be as sensitive
      as MRI. To date, this exciting technology, MBI, has not been used in studies of
      patients with BRCA1/2 genes. We also discuss in more detail the unique
      psychological ramifications of female BRCA1/2 mutation carriers. These women face
      unique choices regarding management of their high risk for breast and ovarian
      cancer that impact their reproductive options. Despite their high levels of
      concern, few female BRCA1/2 mutation carriers consider assisted reproduction
      technologies such as pregnancy surrogate, cryopreservation of oocytes or embryos,
      or implantation genetic diagnosis to select embryos without BCRA1/2 mutation.
      Further research must be undertaken to explore the risk management of patients
      with inherited cancer predisposition and to incorporate these preferences into
      clinical care.

PMID- 19105531
TI  - Colorectal cancer in Crohn's disease--review of a 56-year experience in
      Karolinska Institute University Hospital.
AB  - We previously reported that the frequency of colorectal carcinomas (CRC) in
      Crohn's disease (CD) had increased at this hospital between 1951 and May 1996.
      The aim was to compare the frequency of CRC in CD between June 1996 and September
      2007 to that found between 1951 and May 1996. For that purpose colectomy
      specimens with an IBD-CRC diagnosis filed during the last 11 years were reviewed.
      It was found that 29 patients with IBD developed a CRC at this hospital: 21 had
      CD (or 1.91 cases/year) and the remaining eight, ulcerative colitis (or 0.72
      cases/year). At this hospital, the number of cases of CRC in Crohn's colitis
      increased from 0.28/year between 1951 and the end of 1989, to 1.69 patients/year
      between 1990 and May 1996, and to 1.91 patients/year between June 1996 and
      September 2007 (present report). The marginal increase number of patients with
      CRC in Crohn's colitis/year during the last 11 years at this hospital might be
      only apparent, considering that the incidence of Crohn's disease in the county
      has dramatically increased, and that the localization of Crohn's disease has
      changed in later years, with a predilection for the colon and rectum.

PMID- 19105532
TI  - Immunohistochemical study of fibrosis and adenocarcinoma in dominant-negative p53
      transgenic mice exposed to chrysotile asbestos and benzo(a)pyrene.
AB  - We evaluated the mechanisms using immunohistochemistry whereby chrysotile
      asbestos and benzo(a)pyrene (BaP) instilled intratracheally into lung-specific
      dominant-negative p53 (dnp53) mice might interact in causing lung carcinomas and
      fibrosis. Chrysotile asbestos and benzo(a)pyrene (BaP) were instilled
      intratracheally into lung-specific dominant-negative p53 (dnp53) and control
      mice. The mice were sacrificed at 12 months and their lungs examined for lung
      carcinomas and fibrosis. Immunostains for proteins related to apoptosis,
      fibrogenesis, matrix remodeling and inflammation were performed. The dnp53 mice
      had increased numbers of lung adenocarcinomas with BaP alone and the combination
      of chrysotile and BaP (the latter was additive but not significant). Several
      atypical adenomatous hyperplasia lesions were found in the combined treatment
      group. dnp53 and FVBN control mice developed nodular buds of fibrotic lung tissue
      after chrysotile asbestos exposure that were localized in respiratory
      bronchioles; these lesions had significant increases in immunohistochemical
      staining for TGF-beta, MMP-7 and -9, MIG-1, and SDF-1. Fibrotic lesions in mice
      exposed to chrysotile had increased collagen demonstrated by picrosirius red
      staining. The dnp53 mice with adenocarcinomas had increased SDF-1, TGF-beta, MMP
      9 and -7, Cyclin D, and MIG-1 immunostaining in the chrysotile and combined
      treatment groups. We conclude that BaP and the combination of BaP plus chrysotile
      asbestos are potent inducers of adenocarcinoma in dnp53 mice and that the
      inflammatory cytokines and proteases MMP-7 and -9, MIG-1, and SDF-1, and growth
      factors Cyclin D and TGF-beta are increased in the specific lesions.

PMID- 19105533
TI  - Analysis of spontaneous and streptonigrin-induced sister chromatid exchanges in
      peripheral lymphocytes of aircrew members of international flights.
AB  - In this work, we extend our previous studies concerning mutagen sensitivity in
      flight personnel from commercial airlines by analyzing the frequency of
      spontaneous and streptonigrin (SN)-induced sister chromatid exchanges (SCEs) in
      peripheral blood lymphocytes of 18 long-haul aircrew members from Argentina and
      of 18 control individuals. Statistical analysis revealed no significant
      differences between aircrew and controls in the background level of SCEs (p >
      0.05), which suggests that chronic exposure to cosmic radiation and other
      occupational hazards does not affect SCEs frequency in peripheral lymphocytes of
      aircrews. The fact that almost no correlation was found between cumulative flight
      hours and the yield of spontaneous SCEs in aircrews adds further support to this
      assumption. Therefore, the background SCEs frequency cannot be use as a valid
      biomarker to determine the genotoxic effects of cosmic radiation or other
      occupational hazards exposure in aircrews. Following SN treatment, a significant
      increase in the mean frequency of SCEs was observed in the control group (p <
      0.05) but not in the aircrew group (p > 0.05), suggesting that at the population
      level, aircrew are more resistant to the mutagenic effects of SN than controls.
      The reasons of this resistance remain to be determined. Since cosmic radiation
      had no effect on the background SCEs frequency and no relationship was found
      between cumulative flight hours and SCEs inducer effect by SN in aircrews, a
      direct effect of cosmic radiation on SN resistance should be discarded.

PMID- 19105534
TI  - In vivo evaluation of the toxic effects of pyrimethamine on spermatogenesis in
      male mice.
AB  - Pyrimethamine is known to have antimalarial activities and used clinically in the
      therapy of toxoplasmosis and human immunodeficiency virus-associated pneumonia.
      In this study we aimed to test the effects of pyrimethamine on spermatogenesis in
      mice. For this aim, animals were given pyrimethamine as a single application and
      the doses were 5, 10, 20, and 40 mg/kg. For the spermatogenic effects, the sperm
      shape abnormality, epididymal sperm counts, and testes weights were evaluated at
      the end of days 7, 14, 21, 28, and 35 after single pyrimethamine injection at the
      first day. Pyrimethamine increased the frequency of abnormal sperm shape for all
      studied weeks except the first week and its germ cell stage-specific effects
      correspond to spermatozoa, spermatids, and spermatocytes. It also decreased the
      epididymal sperm counts at the end of days 28 and 35, which corresponds to the
      spermatocyte stage of mouse spermatogenesis.

PMID- 19105535
TI  - Cyclooxygenase-2 inhibition by etoricoxib modulates plasma membrane fluidity in
      rat colon.
AB  - The present study was designed to investigate the effects of a selective
      cycloogenase-2 (COX-2) inhibitor, etoricoxib, on the membrane-specific enzymes,
      lipid composition, and changes in fluidity parameters of rat colonic plasma
      membrane. Two doses of the drug were used, one within its therapeutic anti
      inflammatory range as based on the ED50 value in rats (Eto-1), while the other at
      10 times higher dose relating to the toxicity studies (Eto-2), which have not
      been reported so far. The activity of the membrane alkaline phosphatase was found
      to be increased after treatment with both the doses of etoricoxib as compared to
      the control. The total lipid and the cholesterol content showed a decrease while
      an increase in ganglioside sialic acid content was noted. Phospholipid content
      and the cholesterol-phospholipid molar ratio showed no change in either of the
      treatment groups. Fluorescence polarization studies with diphenylhexatriene
      showed that membrane fluidity was least altered in the isolated brush border
      membrane from colon or in the liposomes prepared from the membrane lipid
      extracts. Also, the translational diffusion studied with pyrene showed that the
      fluidity parameter was decreased as measured by the excimer formation. It is
      concluded that etoricoxib, a new generation COX-2 inhibitor (called the coxibs),
      appeared to be a safe nonsteroidal anti-inflammatory drug (NSAID) in the colonic
      membranes.

PMID- 19105536
TI  - The food and drug administration agrees to classify mercury fillings.
AB  - In the United States Court of Appeals of the District of Columbia Circuit, the
      Appellants Mom's Against Mercury, Connecticut Coalition for Environmental
      Justice, Oregonians for Life, California Citizens for Health Freedom, Kevin J.
      Biggers, Karen Johnson, Linda Brocato, R. Andrew Landerman, and Antia Vazquez
      Tibaul filed a petition for review of Regulatory Inaction by the Food and Drug
      Administration (FDA). On Monday June 2, 2008, the lawsuit was settled with the
      FDA after it agreed to classify mercury fillings. During its negotiation session
      with the Appellants, the FDA indicated that it would change its website on
      mercury fillings. The FDA no longer claims that no science exists about the
      safety of mercury amalgam or that other countries have acted for environmental
      reasons only. On its website, the FDA now states the following: "Dental amalgams
      contain mercury, which may have neurotoxic effects on the nervous systems of
      developing children and fetus." The FDA also states that "Pregnant women and
      persons who may have a health condition that makes them more sensitive to mercury
      exposure, including individuals with existing high levels of mercury bioburden,
      should not avoid seeking dental care, but should discuss options with their
      health practitioner." The FDA decision to classify mercury fillings is a
      reflection of the legislations enacted in Europe and Canada that highlight the
      neurotoxic effects of mercury fillings.

PMID- 19105537
TI  - Photodynamic diagnosis and therapy in gynecology.
AB  - Photodynamic diagnosis (PDD) and therapy (PDT) are modern methods that are
      evaluated in different fields in gynecology. PDD is currently under investigation
      in gynecologic conditions such as cervical intraepithelial neoplasia (CIN),
      vulvar intraepithelial neoplasia (VIN), endometriosis, and ovarian cancer. PDT
      has been successfully evaluated in HPV-related genital dysplasia such as CIN and
      VIN, in genital warts, in local recurrent breast cancer, and for endometrial
      ablation. The aim of this review is to give an overview about current
      applications.

PMID- 19105538
TI  - Antitumor-promoting effects of polyphenolic extracts from seedless and seeded
      Indian grapes.
AB  - Grapes, the widely consumed fruits, are rich in polyphenols. The biological and
      chemopreventive activities of grape seed polyphenols have been demonstrated,
      while similar information regarding crude polyphenolic extracts from whole grapes
      and their components (pulp plus skin, seeds), particularly the seedless
      varieties, is lacking. Cancer chemoprevention can be achieved by inhibition of
      either initiation or promotion/progression stages of carcinogenesis. This study
      involves the determination of the polyphenolic content extracted from green
      (Pandhari sahebi, Thompson seedless) and black cultivars (Bangalore blue, Sharad
      seedless) of Indian grapes and their components (whole grapes, pulp plus skin,
      and seeds). Comparative evaluation of antitumor-promoting effects of seedless and
      seeded grape polyphenolic extracts (GPEs) was carried out in carcinogen-initiated
      and 12-O-tetradecanoylphorbol-13-acetate (TPA)-promoted S/RVCri-ba mouse skin and
      stomach, as well as esophagus of ICRC mice. The yield of crude polyphenolic
      extracts from whole grapes and their components varied between 3% and 51%. The
      total polyphenolic content expressed as mg catechin equivalents/g crude
      polyphenolic extract ranged from 0.47 to 701 in seeded grapes and 1.49 to 28.30
      in seedless varieties. Both seedless and seeded GPEs possessed antitumor
      promoting activity in target tissues of mice as is evident from their ability to
      delay tumor formation along with a significant decrease in tumor multiplicity and
      incidence. Marked and sustained epidermal hyperplasia observed in 7,12
      dimethylbenz(a)anthracene-initiated and TPA-promoted mice was greatly reduced on
      pretreatment with GPE or catechin. The polyphenolic extracts from Sharad seedless
      and seeds of Bangalore blue showed the strongest suppressing activity comparable
      to catechin than the corresponding whole grapes. The results suggest that the
      chemopreventive activity of polyphenols extracted from seedless grape cultivars
      was as effective as that of the seeded variety and these may have beneficial
      effects in disease states, especially cancer.

PMID- 19105539
TI  - Pale sunlight through a dusty lens: physician assistant research.

PMID- 19105540
TI  - Too much attention makes this problem worse.

PMID- 19105541
TI  - Influenza 2008-2009: update your vaccination protocol.

PMID- 19105542
TI  - Multiple myeloma: vague symptoms can challenge diagnostic skills.

PMID- 19105543
TI  - Hidradenitis suppurativa: a disease of apocrine gland physiology.

PMID- 19105544
TI  - Severe stress in an elderly woman causes a temporary "broken" heart.
AB  - This novel cardiac syndrome has clinical features that mimic those of acute
      myocardial infarction. The typical patient is a postmenopausal woman.

PMID- 19105545
TI  - Examining the most popular weight loss diets: how effective are they?
AB  - Patients may swear by a particular diet, but the medical evidence gathered so far
      indicates that for most, keeping lost weight off for at least a year is an
      elusive goal.

PMID- 19105547
TI  - The title search: not just for real estate.

PMID- 19105546
TI  - Scoliosis: a straightforward approach to diagnosis and management.
AB  - Scoliosis should be no more intimidating to manage than acute otitis media. This
      article reviews how to treat patients with the condition before and after
      referral to a specialist.

PMID- 19105548
TI  - Premenstrual dysphoric disorder (PMDD).

PMID- 19105549
TI  - How can I quit smoking?

PMID- 19105550
TI  - A common cause of knee pain in athletic children.

PMID- 19105551
TI  - Case of the month. Hypersensitive carotid sinus syndrome.

PMID- 19105552
TI  - Equal access for fathers?

PMID- 19105553
TI  - Is policy worship causing client neglect?

PMID- 19105554
TI  - Completing the maternity jigsaw.

PMID- 19105555
TI  - The father factor: men can make the difference.

PMID- 19105556
TI  - Men can be a help, not a hindrance.

PMID- 19105557
TI  - Disabled men can be dads, too!

PMID- 19105558
TI  - Fable and fact: young parents fight back.

PMID- 19105559
TI  - Coming soon! The health in pregnancy grant.

PMID- 19105560
TI  - An unplanned hospital birth!

PMID- 19105561
TI  - Brazelton babies: understanding infant behaviour.
AB  - When we work with families, we need to develop a strong, collaborative
      relationship with them in order to support the family system. We can listen to
      and communicate with parents and older children as they can verbalise their likes
      and dislikes. In order to listen to and communicate with babies, we need to
      understand their behaviour, which is their language. The Neonatal Behavioural
      Assessment Scale gives us rich information about the needs of the individual baby
      for their optimal development. We can help parents to facilitate the infant in
      coping with their environment and interactions. Parents enjoy the amazing
      interactive abilities of their infant; and, since the baby is the barometer of
      the situation in the household, we can form an understanding of the needs of the
      baby and the family by using the NBAS.

PMID- 19105562
TI  - Action research: part 2. Testing the new teaching method.

PMID- 19105563
TI  - Midwifery basics: caring for women with medical conditions (3). Haemoglobin
      disorders in pregnancy.

PMID- 19105564
TI  - Campaigning for better birth environments.

PMID- 19105565
TI  - A rollercoaster ride: life as a student midwife.

PMID- 19105566
TI  - A midwife's guide to birth fairies.

PMID- 19105567
TI  - Booked home births and IPPM rates.

PMID- 19105568
TI  - Lynch syndrome and related familial colorectal cancers.
AB  - Lynch syndrome (hereditary non-polyposis colorectal cancer, HNPCC) refers to
      autosomal dominant predisposition to colorectal, endometrial, and a spectrum of
      other cancers. The syndrome is due to heterozygous germ line mutations in one of
      the mismatch repair genes MLH1, MSH2, MSH6, and PMS2. Amsterdam I and II criteria
      for clinical diagnosis and Bethesda guidelines for molecular testing of suspected
      patients usually point out additional families in which there is no evidence of
      mismatch repair deficiency even after screening by microsatellite instability
      analysis and/or immunohistochemistry for mismatch repair proteins. Hence, the
      term "Lynch syndrome" should be restricted to those families with germ line
      mutations in one of the mismatch repair genes. Familial colorectal tumors with no
      evidence of mismatch repair deficiency were shown to be clinically and
      molecularly distinct from classical Lynch syndrome tumors and, therefore, were
      designated "familial colorectal cancer type X" (FCC-X). The predisposing gene(s)
      to FCC-X is as yet unknown, but extensive research is currently underway to
      delineate its etiology. Given the above distinctions, the term hereditary
      nonpolyposis colorectal cancer (HNPCC), which was formerly used to refer to
      clinically diagnosed colorectal cancer families that might or might not have
      mismatch repair deficiency, is being replaced by one of the more informative
      names: Lynch syndrome and FCC-X.

PMID- 19105569
TI  - Tumor protein D52 overexpression and gene amplification in cancers from a mosaic
      of microarrays.
AB  - The tumor protein D52 gene is increasingly recognized to be overexpressed in
      different cancer types, frequently through gain of the corresponding locus at
      chromosome 8q21.13. This review summarizes the literature identifying D52
      overexpression and/or gene amplification in different cancers, as well as recent
      publications directly analyzing D52 functions. Since D52 overexpression is
      increasingly being identified in tumors of different cellular origins, this is
      likely to perturb fundamental cell properties common to different cell types.
      Furthermore,since increased D52 expression occurs at different stages of
      tumorigenesis and progression, this could contribute to these processes through
      multiple mechanisms. Although functions are beginning to emerge from targeted
      studies, the pathways through which D52 overexpression contributes to cell
      transformation and the molecular interactions required remain undefined. In
      summary, while targeting D52 overexpression could provide therapeutic benefits in
      many cancer types, this will require an improved understanding of D52's cellular
      and molecular functions.

PMID- 19105570
TI  - Role for the cAMP-protein kinase A signaling pathway in suppression of antitumor
      immune responses by regulatory T cells.
AB  - CD4+CD25+ regulatory T (Treg) cells are engaged in the maintenance of
      immunological self-tolerance and suppressive control of excessive immune
      responses to foreign antigens. Furthermore, Treg cells infiltrate tumor tissues
      and may impede immune surveillance against cancer and hamper the development of
      an effective antitumor immunity. Depletion of Treg cells in animal models has
      been demonstrated to provoke tumor immunity. Attenuation of Treg-mediated
      suppression is therefore an interesting strategy to enhance antitumor responses.
      We recently found that adaptive Treg cells express COX-2 and suppress responder T
      cells in a PGE2-cAMP-dependent manner, which can be reversed by COX-2 inhibitors
      or EP-receptor antagonists. The same mechanism also appeared to be operative in
      patients with colorectal cancer where treatment with COX-inhibitor or cAMP
      antagonist enhanced antitumor immune responses to the same extent as depletion of
      Treg cells. This provides mechanism-based opportunities for pharmacological
      intervention to interfere with Treg immunosuppression. In this review we will
      discuss key mechanisms used by Treg cells to suppress antitumor immunity, with
      emphasis on the cAMP-PKA pathway. We will also highlight some of the roles of
      Treg cells in cancer.

PMID- 19105571
TI  - A brief history of: cloning.

PMID- 19105572
TI  - Danger: walking while working. Does a new desk really solve the problem of having
      no time to exercise?

PMID- 19105573
TI  - Slender in the grass.

PMID- 19105574
TI  - AHIP: surely 30% possible.

PMID- 19105576
TI  - Largest patient-satisfaction measurement firms. Ranked by total number of
      engagements in 2007.

PMID- 19105575
TI  - No time for napping. Time to wake up those in charge of fixing healthcare, let
      young providers get their rest.

PMID- 19105577
TI  - Interference effects and the consequences of recognition failures and successes.
AB  - This investigation examined the contribution of memory awareness to interference,
      conceptualized as response competition that arises from the encoding of materials
      similar in appearance. Subjects performed incidental encoding tasks (counting
      vowels, counting syllables, and word association) on targets and non-targets that
      were orthographically similar (experimental condition) or dissimilar (control
      condition). The tasks were intended to make the memories of the studied words at
      test more or less accessible to subjects' awareness. During the test, fragments
      of the targets were intermixed with fragments of nonstudied words, and the task
      was to complete fragments with studied words or, in the absence of such memories,
      with the first words that came to mind. Response competition was expected to
      produce a blocking effect, consisting of fewer correct completions and more
      intrusions (or null responses) in the experimental condition than in the control
      condition. When the overall accessibility of the studied, orthographically
      similar words was optimized by the semantic association task, responses
      recognized as studied exhibited both more intrusions and fewer correct
      completions than in the control condition. When the accessibility of these words
      was curtailed by the vowel counting task, only unrecognized correct completions
      after the proactive interference treatment tended to be lower than in the control
      condition. These results suggest that memory awareness can modulate interference
      conceptualized as response competition.

PMID- 19105578
TI  - The early bird does not get the worm: time-of-day effects on college students'
      basic cognitive processing.
AB  - We conducted a neuropsychological and cognitive assessment study to determine
      whether time of day affects cognitive performance. We measured executive control
      (fluency), processing speed, semantic memory, and episodic memory performance. We
      followed 56 students across 3 different times of day, testing performance on
      vocabulary, fluency, processing speed, and episodic memory. Results showed an
      advantage for fluency and digit symbol task performance in the afternoon and
      evening testing times relative to morning testing (regardless of testing order),
      but that time of day did not affect semantic or episodic memory performance.
      These results suggest that optimal executive functioning and processing speed may
      occur for typical college students in the afternoon and evening regardless of
      time-of-day preference.

PMID- 19105579
TI  - A unified theory of all-or-none and incremental learning processes via a new
      application of study-test-rest presentation programs and psychophysiological
      measures.
AB  - The all-or-none (AON) versus incremental learning debate was newly examined using
      heart rate (HR) and galvanic skin response (GSR) under varied study-test-rest
      (STR) presentation programs. Fifty university students learned a list of 20
      consonant-vowel-consonant-2-digit pairs in a simple learning situation. Three
      item types were analyzed: items learned, never learned, and in-between. Learning
      performance moved from the unlearned to the learned state in one jump in the AON
      fashion, despite nonsignificant incremental trends during some precriterion
      trials. New HR and GSR phenomena were unveiled: Persistent relaxation occurred
      abruptly a few trials before actual learning. The relaxation attained
      unconsciously, after intense conscious effort, might facilitate mastery.
      Unlearned items lacked such jumps for all 3 response measures. Of all conditions
      examined, STTTTTTT produced the most efficient learning with the greatest
      attention (HR), most relaxation (GSR), and least test anxiety (interprogram
      comparisons). By using Estes' mathematical derivations, a unified theory is
      advocated: AON learning can be regarded as a special case of incremental
      learning. The former is associated with very simple learning situations, whereas
      the latter involves complex learning situations. The 2 positions are not
      irreconcilable; instead, they represent 2 extremes of such experiments, the
      simple and complex learning situations.

PMID- 19105580
TI  - Effect of context and personality on the forgiveness schema.
AB  - This study examined the extent to which the type of aggressive behavior affected
      the impact of circumstances of the aggression on the victim's willingness to
      forgive. The participants were 97 adults aged 17 to 68 years. They expressed
      willingness to forgive in 3 contexts: breaking up of a love affair, gossiping at
      work, and collision during a game. As hypothesized, apologies and intent had more
      impact in the physical aggression condition than in the psychological aggression
      conditions, cancellation of consequences had more impact in the psychological
      aggression conditions than in the physical aggression condition, the structure of
      the forgiveness schema varied as a function of the type of harmful situation, and
      participants with a higher score in emotional stability and agreeableness were
      more willing to forgive than participants with a lower score.

PMID- 19105581
TI  - Are theories to be evaluated in isolation or relative to alternatives? An
      abductive view.
AB  - Although it is distinct from induction and deduction, abduction is often mistaken
      for them. The initial stage of abduction, or novel hypothesis abduction, has 2
      components. The first concerns providing novel hypotheses that explain the
      pattern of data; the second suggests that the novel hypothesis should be accepted
      to the extent that it is the best available hypothesis. The second component is
      known as inference to the best explanation. Others have shown how novel
      hypothesis abduction provides an important type of reasoning for generating novel
      hypotheses. Our concern is with evaluating already formed abductions to determine
      which is best, using inference to the best explanation in connection with
      theories. We call this competing theories abduction. Competing theories abduction
      suggests that theories should be evaluated in relation to other theories rather
      than in isolation, as suggested by some philosophers and psychologists. In
      psychology this is demonstrated in connection with 2 widely accepted forms of
      relativism: the logical possibilities view and unique standards relativism.

PMID- 19105582
TI  - Pluto behaving badly: false beliefs and their consequences.
AB  - We exposed college students to suggestive materials in order to lead them to
      believe that, as children, they had a negative experience at Disneyland involving
      the Pluto character. A sizable minority of subjects developed a false belief or
      memory that Pluto had uncomfortably licked their ear. Suggestions about a
      positive experience with Pluto led to even greater acceptance of a lovable ear
      licking episode. False beliefs and memories had repercussions; those seduced by
      the bad suggestions were not willing to pay as much for a Pluto souvenir. These
      findings are among the first to demonstrate that false beliefs can have
      repercussions for people, meaning that they can influence their later thoughts,
      beliefs, and behaviors.

PMID- 19105583
TI  - Integrating learning, emotion, behavior theory, development, and neurobiology:
      the enduring legacy of Abram Amsel (1922-2006).

PMID- 19105584
TI  - The efficacy and safety of cilomilast in COPD. Forward.

PMID- 19105586
TI  - L-carnitine and its derivatives: exciting experimental and clinical data are
      accumulating in the treatment of ocular disorders.

PMID- 19105585
TI  - The efficacy and safety of cilomilast in COPD.
AB  - The aim of this review is to present the clinical data on the efficacy and safety
      of cilomilast in patients with chronic obstructive pulmonary disease (COPD). Over
      6000 COPD patients received cilomilast during an extensive clinical development
      programme performed by GlaxoSmithKline (GSK).Five phase III randomized, double
      blind, placebo-controlled, parallel-group pivotal studies were conducted in
      poorly reversible patients (<15% or <200 mL improvement over baseline in forced
      expiratory volume in 1 second (FEV(1)) after salbutamol). Patients were
      randomized to receive oral cilomilast 15 mg (n = 2088) or placebo (n = 1408)
      twice daily for 24 weeks. The co-primary efficacy variables were changes from
      baseline in trough (predose) FEV(1) and in total score of the St George's
      Respiratory Questionnaire (SGRQ).Additional studies were performed to investigate
      the anti-inflammatory actions of cilomilast by measuring inflammatory cells and
      mediators in biopsies and induced sputum; to assess the long-term effects of
      cilomilast; to assess the cardiac safety of cilomilast; and to assess the
      efficacy of cilomilast on hyperinflation. Results from one of the phase III and
      from one supportive study have been previously published.In the phase III pivotal
      studies, when averaged over 24 weeks, the mean change from baseline in FEV(1) in
      the cilomilast group showed improvement compared with placebo in all studies
      (range 24-44 mL treatment difference). When averaged over 24 weeks, there was a
      similar improvement in the mean total SGRQ score in both treatment groups with a
      decrease ranging from -1.8 to -4.2 units in the cilomilast group and 0.4 to -4.9
      units in the placebo group. Only one study, however, showed both a statistically
      and clinically meaningful difference between the two treatment groups (treatment
      difference -4.1 units; p < 0.001). Although cilomilast was shown to reduce COPD
      exacerbations in some of these studies, there was no effect on the incidence of
      COPD exacerbations in a study specifically powered to detect a difference
      compared with placebo.No significant change was found in the primary endpoints of
      the anti-inflammatory studies, although some anti-inflammatory activity was
      detected, including a reduction in tissue CD8+ T lymphocytes and CD68+
      macrophages in airway biopsies. In addition, studies did not demonstrate a
      consistent significant effect of cilomilast on hyperinflation.In all studies,
      adverse events associated with the gastrointestinal body system were reported
      more frequently in the cilomilast group than the placebo group and predominantly
      occurred within the first 2 weeks of initiating cilomilast therapy.During the
      cilomilast development programme a number of different endpoints were
      investigated to characterize the efficacy and safety of this second-generation
      phosphodiesterase 4 inhibitor. Safety assessments throughout the late-phase
      programme did not reveal any evidence of serious safety concerns with the use of
      cilomilast. Previous studies in phase II and early phase III had shown
      improvements in efficacy endpoints and some evidence of an anti-inflammatory
      mechanism of action. However, subsequent phase III studies failed to definitively
      confirm the earlier programme results, which led to termination of the
      development of cilomilast.

PMID- 19105587
TI  - The aging eye and the role of L-carnitine and its derivatives.
AB  - The majority of ocular pathologies originate from a functional deterioration of
      intraocular tissues. This age-related deterioration often occurs as a result of
      changes within the eye. There is growing interest in the role of natural or
      synthetic compounds, such as carnitine, for blocking, or slowing, the progress of
      this deterioration. L-carnitine and its derivatives are involved in numerous
      physiological reactions, including sugar aerobic metabolism, oxidative
      phosphorylation, fatty acid oxidation and osmosis. While carnitine levels in
      human ocular tissue are unknown, animal studies indicate that carnitine is
      differentially distributed within the eye with the highest concentrations
      reported in the iris, ciliary body and the choroid-retina. In patients with age
      related macular degeneration (AMD), acetyl-L-carnitine improved four parameters
      of visual function, including visual field mean defect, visual acuity, foveal
      sensitivity and ocular fundus alterations. L-carnitine has also demonstrated
      antioxidant properties in animal models of oxidative damage. This article reviews
      the potential use of L-carnitine and its derivatives in age-related ocular
      pathologies, such as AMD, cataract, glaucoma and dry eye syndrome.

PMID- 19105588
TI  - Ocular disorders secondary to systemic disease and the potential role of
      carnitines.
AB  - L-carnitine has a wide-ranging role in several physiological processes, but
      perhaps most significantly in long-chain fatty acid oxidation in the
      mitochondrial matrix. Osmolytic (or osmoprotective) properties have also been
      suggested for the compound. Importantly, the ability of L-carnitine to improve
      insulin sensitivity in insulin-resistant diabetic patients may, together with the
      agent's antioxidant and antiapoptotic activity, provide some degree of protection
      against the progression of diabetic retinopathy. L-carnitine may also protect
      against the deleterious effects of ocular ischaemic syndrome, and, indeed, acetyl
      L-carnitine has been shown to significantly improve retinal damage and visual
      acuity in patients with monolateral or bilateral retinal artery occlusion. The
      antioxidant, antiapoptotic and osmolytic properties of L-carnitine also suggest
      that this agent may have valuable clinical utility in neurotrophic keratopathy
      and bullous keratopathy. Thus, further detailed investigation of the important
      clinical potential of L-carnitine in various ocular conditions (e.g. diabetic
      retinopathy, ocular ischaemic syndrome, neurotrophic keratopathy and bullous
      keratopathy) that occur secondary to systemic diseases is now clearly warranted.

PMID- 19105589
TI  - Inherited ocular disorders, ophthalmic procedures and carnitines.
AB  - L-carnitine plays a role in physiological reactions throughout the body,
      including sugar aerobic metabolism, oxidative phosphorylation and, most
      importantly, fatty acid oxidation. In addition, L-carnitine has antiapoptotic,
      antioxidative and osmolytic properties, which may be useful in the treatment of
      ocular pathologies (e.g. retinitis pigmentosa [RP] and keratoconus), in corneal
      tissue repair and in ophthalmic procedures (e.g. photorefractive keratectomy and
      laser-assisted subepithelial keratectomy [LASEK]). Preliminary studies have
      suggested that L-carnitine supplementation may be useful in patients with RP.
      Although studies are warranted to ascertain the benefit of L-carnitine in the
      LASEK procedure, potentially it could be used instead of alcohol to facilitate
      epithelial detachment and as a hypo-osmotic solution in the fluid filler used in
      therapeutic photoablation. Furthermore, its antiapoptotic properties may improve
      cellular migration, proliferation and adhesion of keratocytes, epithelial cells
      and endothelial cells, which may be useful in the corneal repair process.
      Similarly, L-carnitine in high concentrations may prove useful in cross-linking
      parasurgical treatment of keratoconus, owing to its osmolytic and non-cytotoxic
      properties.

PMID- 19105590
TI  - L-carnitine and its derivatives: a promising future in the treatment of ocular
      disorders.

PMID- 19105591
TI  - Glyphosate formulations induce apoptosis and necrosis in human umbilical,
      embryonic, and placental cells.
AB  - We have evaluated the toxicity of four glyphosate (G)-based herbicides in Roundup
      formulations, from 10(5) times dilutions, on three different human cell types.
      This dilution level is far below agricultural recommendations and corresponds to
      low levels of residues in food or feed. The formulations have been compared to G
      alone and with its main metabolite AMPA or with one known adjuvant of R
      formulations, POEA. HUVEC primary neonate umbilical cord vein cells have been
      tested with 293 embryonic kidney and JEG3 placental cell lines. All R
      formulations cause total cell death within 24 h, through an inhibition of the
      mitochondrial succinate dehydrogenase activity, and necrosis, by release of
      cytosolic adenylate kinase measuring membrane damage. They also induce apoptosis
      via activation of enzymatic caspases 3/7 activity. This is confirmed by
      characteristic DNA fragmentation, nuclear shrinkage (pyknosis), and nuclear
      fragmentation (karyorrhexis), which is demonstrated by DAPI in apoptotic round
      cells. G provokes only apoptosis, and HUVEC are 100 times more sensitive overall
      at this level. The deleterious effects are not proportional to G concentrations
      but rather depend on the nature of the adjuvants. AMPA and POEA separately and
      synergistically damage cell membranes like R but at different concentrations.
      Their mixtures are generally even more harmful with G. In conclusion, the R
      adjuvants like POEA change human cell permeability and amplify toxicity induced
      already by G, through apoptosis and necrosis. The real threshold of G toxicity
      must take into account the presence of adjuvants but also G metabolism and time
      amplified effects or bioaccumulation. This should be discussed when analyzing the
      in vivo toxic actions of R. This work clearly confirms that the adjuvants in
      Roundup formulations are not inert. Moreover, the proprietary mixtures available
      on the market could cause cell damage and even death around residual levels to be
      expected, especially in food and feed derived from R formulation-treated crops.

PMID- 19105593
TI  - Structure-activity relationships for degradation reaction of 1-beta-o-acyl
      glucuronides: kinetic description and prediction of intrinsic electrophilic
      reactivity under physiological conditions.
AB  - 1-beta-O-Acyl glucuronides (betaGAs) are potentially reactive metabolites capable
      of binding to proteins, and they have been implicated in adverse drug reactions
      of the carboxylic acid drugs. To explore their electrophilic reactivity, we
      studied structure-activity relationships (SARs) to characterize the factors
      affecting the degradation rate constants (k values) of betaGAs and ultimately to
      predict k values of structurally diverse betaGAs. Twenty-seven betaGAs and four
      related compounds were synthesized, and their k values were determined under
      physiological conditions (pH 7.4 and 37 degrees C). 1-beta-O-Benzoyl glucuronide
      (BAGA) and glucopyranoside (BAG) showed almost the same k values, whereas their 1
      alpha-O-benzoyl isomers degraded approximately 40-fold faster than BAGA and BAG.
      BAGA methyl ester showed almost the same rate constant as BAGA in the cleavage of
      their 1-beta-O-benzoyl linkages. A pH-log k profile obtained indicated kinetics
      catalyzed by both specific and general bases. The log k of betaGAs derived from m
      and p-substituted benzoic acids correlated with Hammett's sigma constants. A
      similar correlation was observed with delta(COOH), (1)H NMR chemical shifts of
      the parent benzoic acids including ones with less sterically bulky o
      substituents. Alternative descriptors of delta(CO) and delta((CO)OH), (13)C
      chemical shifts for ester carbonyl carbons of betaGAs and for carbonyl carbons of
      the parent benzoic acids, respectively, correlated well with the log k of all 16
      betaGAs derived from benzoic acids including ones with bulkier o-substituents. Of
      the betaGA isomers derived from (2R)- and (2S)-alpha-methyl-4-biphenylylacetic
      acid, the (2R)-isomer degraded approximately 2-fold faster than the (2S)-isomer.
      The alpha-methyl group in the (2S)-isomer would encumber the intramolecular acyl
      migration. The log k of betaGAs derived from n-aralkyl carboxylic acids and of
      the (2R)-isomer correlated with their delta(COOH). However, the log k of betaGAs
      derived from alpha,alpha-dimethyl- and alpha,alpha-diethyl-4-biphenylylacetic
      acids deviated downward from the regression line, probably due to a steric
      effect. The diversity and complexity of k values were discussed with respect to
      the electrophilicity of the ester carbonyl carbons of betaGAs and the steric
      hindrance around them.

PMID- 19105592
TI  - Oxidation of 4-chlorobiphenyl metabolites to electrophilic species by
      prostaglandin H synthase.
AB  - Hormonally sensitive tissues, like the prostate, ovary, and breast, increasingly
      studied as targets of environmental chemicals, are sources of an enzyme
      potentially capable of transforming and activating xenobiotics to highly reactive
      metabolites. Our study specifically addresses the question of whether
      prostaglandin H synthase (PGHS) can activate phenolic metabolites of
      polychlorinated biphenyls (PCBs). We found that human recombinant PGHS-2
      catalyzed the oxidation of ortho (2',3'- and 3',4'-) and para (2',5'-) dihydroxy
      4-chlorobiphenyl metabolites to their corresponding quinones. These were trapped
      in situ with N-acetyl cysteine, and the reaction products were isolated and
      characterized by liquid chromatography coupled mass spectrometry and (1)H and
      heteronuclear ((1)H-(13)C) nuclear magnetic resonance spectroscopy. Both mono-
      and di-N-acetyl cysteine Michael addition adducts were identified, with the 2',3'
      and 2',5'-dihydroxy metabolites predominantly forming mono-N-acetyl cysteine
      adducts, while the 3',4'-dihydroxy predominantly formed disubstituted N-acetyl
      cysteine adducts. These studies clearly demonstrate that the phenolic metabolites
      of these environmental pollutants are activated by PGHS, as cosubstrates, to
      highly reactive electrophilic PCB quinones, with a potential for protein and DNA
      damage, especially in nonhepatic tissues where the enzyme is found.

PMID- 19105594
TI  - Characterization of reactive intermediates by multinuclear diffusion-ordered NMR
      spectroscopy (DOSY).
AB  - Nuclear magnetic resonance (NMR) is the most powerful and widely utilized
      technique for determining molecular structure. Although traditional NMR data
      analysis involves the correlation of chemical shift, coupling constant, and NOE
      interactions to specific structural features, a largely overlooked method
      introduced more than 40 years ago, pulsed gradient spin-echo (PGSE), measures
      diffusion coefficients of molecules in solution, thus providing their relative
      particle sizes. In the early 1990s, the PGSE sequence was incorporated into a two
      dimensional experiment, dubbed diffusion-ordered NMR spectroscopy (DOSY), in
      which one dimension represents chemical shift data while the second dimension
      resolves species by their diffusion properties. This combination provides a
      powerful tool for identifying individual species in a multicomponent solution,
      earning the nickname "chromatography by NMR". In this Account, we describe our
      efforts to utilize DOSY techniques to characterize organometallic reactive
      intermediates in solution in order to correlate structural data to solid-state
      crystal structures determined by X-ray diffraction and to discover the role of
      aggregate formation and solvation states in reaction mechanisms. In 2000, we
      reported our initial efforts to employ DOSY techniques in the characterization of
      reactive intermediates such as organolithium aggregates. Since then, we have
      explored DOSY experiments with various nuclei beyond (1)H, including (6)Li,
      (7)Li, (11)B, (13)C, and (29)Si. Additionally, we proposed a diffusion
      coefficient-formula weight relationship to determine formula weight, aggregation
      number, and solvation state of reactive intermediates. We also introduced an
      internal reference system to correlate the diffusion properties of unknown
      reactive intermediates with known inert molecular standards, such as aromatic
      compounds, terminal olefins, cycloolefins, and tetraalkylsilanes. Furthermore, we
      utilized DOSY to interpret the role of aggregation number and solvation state of
      organometallic intermediates in the reactivity, kinetics, and mechanism of
      organic reactions. By utilizing multinuclear DOSY methodologies at various
      temperatures, we also correlated solid-state X-ray structures with those in
      solution and discovered new reactive complexes, including a monomeric boron
      enolate, a product-inhibition aggregate, and a series of intermediates in the
      vinyl lithiation of allyl amines. As highlighted by our efforts, DOSY techniques
      provide practical and feasible NMR procedures and hold the promise of even more
      powerful insights when extended to three-dimensional experiments.

PMID- 19105595
TI  - Viroids: uniquely simple and tractable models to elucidate regulation of cell-to
      cell trafficking of RNA.
AB  - Cell-to-cell trafficking of RNA is an emerging biological principle that
      integrates systemic gene regulation, viral infection, cellular antiviral
      response, and cell-to-cell communication. The mechanisms regulating this
      trafficking remain to be understood. A testable hypothesis is that many RNAs have
      distinct structural motifs to direct trafficking across various cellular
      boundaries. The identification of structural motifs in a noncoding viroid RNA
      required for trafficking between specific cell types in a plant provides
      compelling genetic evidence to support this hypothesis. Here we discuss the
      unique features of viroids as well as experimental data to demonstrate these RNAs
      as simple and highly tractable models to elucidate the general mechanisms of RNA
      trafficking.

PMID- 19105597
TI  - Nanofibers as carrier systems for antimicrobial microemulsions. Part I:
      fabrication and characterization.
AB  - Antimicrobial nanofibers were prepared by solubilizing an antimicrobial essential
      oil (eugenol; 0.75-1.5 wt %) in surfactant micelles (Surfynol 465; 5-10 wt %) to
      form eugenol-containing microemulsions. Microemulsions were mixed with a nonionic
      synthetic polymer (poly(vinyl alcohol), PVA; M(w) = 130 kDa, degree of hydrolysis
      approximately 87%) and solutions subjected to electrospinning to induce nanofiber
      formation. Solution properties, fiber morphology, and composition of nanofibers
      were determined. The surface conductivity and viscosity of the polymer solutions
      increased, while surface tension decreased as both surfactant and eugenol
      concentration increased. Material deposited on the collector plate consisted
      primarily of nanofibers with a circular cross section with some surface
      roughness, although some bead defects were observed. The mean fiber diameters
      ranged from 57 to 126 nm with fibers having a broad diameter distribution (10-280
      nm). The mean diameter of the nanofibers decreased with increasing surfactant
      concentration and decreasing eugenol concentration. Transmission electron
      microscopy indicated that microemulsion droplets were homogenously dispersed
      throughout the nanofibers. Results suggest that electrospun nanofibers may serve
      as carrier vehicles for microemulsions containing solubilized lipophilic
      functional compounds such as bioactives, antimicrobials, antioxidants, flavors,
      and pharmaceuticals.

PMID- 19105598
TI  - Matrix-assisted colloidosome reverse-phase layer-by-layer encapsulating
      biomolecules in hydrogel microcapsules with extremely high efficiency and
      retention stability.
AB  - The layer-by-layer (LbL) polyelectrolyte self-assembly encapsulation method has
      attracted much interest because of its versatility to use various polymers for
      capsule formation, ability to encapsulate different templates, and capability to
      control capsule permeability. Traditionally, the LbL method was performed in
      water as solvent and limited to poorly or non-water-soluble templates. Using the
      matrix-assisted LbL method, complex mixtures of water-soluble proteins or DNA
      could be encapsulated within agarose microbeads templates but leakage of
      biomolecules into the water phase during the LbL process results in low
      encapsulation efficiency. Recently, the reverse-phase LbL (RP-LbL) method was
      introduced to perform LbL and encapsulation of water-soluble templates in organic
      solvents, thus preventing the templates from dissolving and allowing high
      encapsulation efficiency. However, encapsulation of complex mixtures of
      biomolecules or other substances with quantitative encapsulation efficiency
      remained impossible. Here we present a new approach for encapsulation of
      biomolecules or complex mixtures thereof with almost 100% encapsulation
      efficiency. The ability of our method to achieve high encapsulation efficiency
      arises from the combination of two strategies. (1) Using microparticles as
      surface stabilizer to create stable biomolecule-loaded hydrogel microbeads,
      termed matrix-assisted colloidosome (MAC), that are able to disperse in oil and
      organic solvents. (2) Using the RP-LbL method to fabricate polymeric capsule
      "membranes", thereby preventing diffusion of the highly water-soluble
      biomolecules. Using an oil phase during emulsification and an organic solvent
      phase during encapsulation could completely prevent leakage of water-soluble
      biomolecules and almost 100% encapsulation efficiency is achieved. Microcapsules
      fabricated with our method retained nearly 100% of encapsulated proteins during a
      7 day incubation period in water. The method was demonstrated on model proteins
      and may be extended to other biomolecules or mixtures. Our method is a valuable
      addition to the family of encapsulation techniques and can significantly
      contribute to the fields of bioreactors and bioanalytical microcapsules.

PMID- 19105596
TI  - Hydrogen peroxide decreases endothelial nitric oxide synthase promoter activity
      through the inhibition of Sp1 activity.
AB  - We have previously shown that endothelial nitric oxide synthase (eNOS) promoter
      activity is decreased in endothelial cells in response to the addition of
      hydrogen peroxide (H(2)O(2)), and this involves, at least in part, the inhibition
      of AP-1 activity. Thus, the objective of this study was to determine if other cis
      element(s) and transcription factor(s) are involved in the oxidant-mediated
      downregulation of eNOS. Our initial experiments indicated that although H(2)O(2)
      treatment increased eNOS mRNA levels in ovine pulmonary arterial endothelial
      cells (OPAECs), there was a significant decrease in the promoter activity of an
      eNOS promoter construct containing 840 bp of upstream sequence. However, a
      truncated promoter construct that lacked the AP-1 element (650 bp) was also
      inhibited by H(2)O(2). A similar effect was observed when the 650 bp human eNOS
      promoter construct was transfected into human PAECs. We also found that although
      exposure of the cells to PEG-catalase prevented the inhibitory effect on eNOS
      promoter activity, the hydroxyl radical scavenger, deferoxamine myslate, did not.
      Nor could we identify an increase in hydroxyl radical levels in cells exposed to
      H(2)O(2). Exposure of PAECs caused a significant increase in labile zinc levels
      in response to H(2)O(2). As the eNOS promoter has a cis-element for Sp1 binding,
      we evaluated the role of Sp1 in response to H(2)O(2). As previously reported,
      mutation of the Sp1 consensus lead to the complete loss of eNOS promoter
      activity, confirming the key role of Sp1 in regulating basal eNOS promoter
      activity. In addition, we found, using electrophoretic mobility and supershift
      assays, that H(2)O(2) decreased Sp1 binding. Finally, using chromatin
      immunoprecipitation analysis, we found a significant decrease in Sp1 binding to
      the eNOS promoter in vivo in response to treatment with H(2)O(2). Together, these
      data suggest that the inhibition of Sp1 activity, possibly through loss of zinc
      in the protein, plays a role in the H(2)O(2)-induced inhibition of eNOS promoter
      activity.

PMID- 19105599
TI  - Shear stress-mediated adhesion of acute myeloid leukemia and KG-1 cells to
      endothelial cells involves functional P-selectin.
AB  - Acute myeloid leukemia (AML) shows malignant behavior through the ability of
      immature cells to circulate in blood and to invade peripheral tissues. Whereas
      binding of human AML cells to endothelial cells (ECs) through E-selectin has been
      shown to occur using classical adhesion assays, little is known about the ability
      of endothelial P-selectin to support this process. We therefore characterized the
      ability of AML blasts and KG-1 cells to bind to endothelial selectin type
      ligands. Flow cytometry revealed that, in addition to various integrin adhesion
      receptors, AML cells regularly express the P-selectin glycoprotein ligand (PSGL)
      1, a ligand for P- and E-selectin on ECs. In parallel flow chambers, AML cells
      both rolled and adhered to TNF-alpha pretreated human umbilical vein endothelial
      cells (HUVECs). Pretreatment of HUVECs with anti-P- or anti-E-selectin function
      blocking antibodies significantly reduced both, rolling and subsequent arrest of
      primary AML cells. Intravital microscopy of i.v. injected fluorescence-labeled KG
      1 cells into P-selectin deficient or wild type mice confirmed a significant role
      of endothelial P-selectin in the binding of human primary AML cells to ECs also
      in vivo. Thus, the currently available data suggest a role of P- and E-selectin
      in coordinated circulation of AML cells. Thus, P- or E-selectin mediated adhesion
      of AML cells may provide a target for the development anti-leukemic therapies.

PMID- 19105600
TI  - Plasmonic gallium nanoparticles on polar semiconductors: interplay between
      nanoparticle wetting, localized surface plasmon dynamics, and interface charge.
AB  - Ga nanoparticles supported on large band gap semiconductors like SiC, GaN, and
      ZnO are interesting for plasmon-enhanced UV-emitting solid-state devices. We
      investigate the influence of the polarity of the SiC, GaN, and ZnO wurtzite
      semiconductors on the wetting of Ga nanoparticles and on the resulting surface
      plasmon resonance (SPR) by exploiting real time plasmonic ellipsometry. The
      interface potential between polar semiconductors (SiC, GaN, and ZnO) and
      plasmonic nanoparticles (gallium) is shown to influence nanoparticle formation
      dynamics, geometry, and consequently the SPR wavelength. We invoke the Lippman
      electrowetting framework to elucidate the mechanisms controlling nanoparticle
      dynamics and experimentally demonstrate that the charge transfer at the Ga
      nanoparticle/polar semiconductor interface is an intrinsic method for tailoring
      the nanoparticle plasmon resonance. Therefore, the present data demonstrate that
      for supported nanoparticles, surface and interface piezoelectric charge of polar
      semiconductors also affects SPR along with the well-known effect of the media
      refractive index.

PMID- 19105602
TI  - Quadrupole-time-of-flight mass spectrometer modified for higher-energy
      dissociation reduces protein assemblies to peptide fragments.
AB  - The gas-phase dissociation of protein assemblies is becoming crucial for the
      application of mass spectrometry to structural biology. However certain aspects
      of the dissociation mechanism remain elusive. Moreover, many protein complexes
      resist dissociation at the energies accessible with current instrumentation. Here
      we report new insights into the collision-induced dissociation mechanism of
      protein assemblies. By holding activation energy constant and varying the charge
      state of the precursor ion, we show that the total charge of the precursor ion
      dramatically influences the internal energy required to dissociate monomers from
      the protein assembly. Furthermore, we have developed a modified quadrupole-time
      of-flight instrument capable of accessing activation energies higher than
      previously possible. Under these conditions, protein assemblies eject subunits
      with excess internal energy that subsequently fragment into peptides. Together,
      these data indicate that the non-covalent dissociation is limited by the amount
      of charge available and not merely the activation energy, and they project the
      exciting possibility of extracting sequence information directly from intact
      protein complexes in the gas phase.

PMID- 19105603
TI  - Nondestructive and noninvasive assessment of mechanical properties in heart valve
      tissue engineering.
AB  - Despite recent progress, mechanical behavior of tissue-engineered heart valves
      still needs improvement when native aortic valves are considered as a benchmark.
      Although it is known that cyclic straining enhances tissue formation, optimal
      loading protocols have not been defined yet. To obtain a better understanding of
      the effects of mechanical conditioning on tissue development, mechanical behavior
      of tissue constructs should be monitored and controlled during culture. However,
      currently used methods for mechanical characterization (e.g., tensile and
      indentation tests) are destructive and are only performed at the end-stage of
      tissue culture. In this study, an inverse experimental-numerical approach was
      developed that enables a noninvasive and nondestructive assessment of mechanical
      properties of engineered heart valves. The applied pressure and volumetric
      deformation of an engineered heart valve were measured during culture, and served
      as input for the estimation of mechanical properties using a computational model.
      To validate the method, six heart valves were cultured, and the mechanical
      properties obtained from the inverse experimental-numerical approach were in good
      agreement with uniaxial tensile test data. The method provides a real-time,
      noninvasive and nondestructive functionality and quality check of tissue
      engineered heart valves and can be used to monitor and control the evolution of
      mechanical properties during tissue culture.

PMID- 19105604
TI  - Mechanically robust and bioadhesive collagen and photocrosslinkable hyaluronic
      acid semi-interpenetrating networks.
AB  - In this work, we present a class of hydrogels that leverage the favorable
      properties of the photo-cross-linkable hyaluronic acid (HA) and semi
      interpenetrating collagen components. The mechanical properties of the semi
      interpenetrating-network (semi-IPN) hydrogels far surpass those achievable with
      collagen gels or collagen gel-based semi-IPNs. Furthermore, the inclusion of the
      semi-interpenetrating collagen chains provides a synergistic mechanical
      improvement over unmodified HA hydrogels. Collagen-HA semi-IPNs supported
      fibroblast adhesion and proliferation and were shown to be suitable for cell
      encapsulation at high levels of cell viability. To demonstrate the utility of the
      semi-IPNs as a microscale tissue engineering material, cell-laden microstructures
      and microchannels were fabricated using soft lithographic techniques. Given their
      enhanced mechanical and biomimetic properties, we anticipate that these materials
      will be of value in tissue engineering and three-dimensional cell culture
      applications.

PMID- 19105605
TI  - Characterization of individual ag nanoparticles and their chemical environment.
AB  - Silver nanoparticles (NPs) of approximately 5 nm diameter deposited in a single
      layer on glycine were examined with cluster secondary ion mass spectrometry
      (SIMS) in the event-by-event bombardment-detection mode. The projectiles used
      were Au(3)(+), C(60)(+), and Au(400)(4+) with impact energies of 34, 26, and 136
      keV, respectively. The highest secondary ion yields were obtained with
      Au(400)(4+). The method presented can test single or multilayer organization and
      determine surface coverage. NPs are identified one-by-one for chemical
      composition. Chemical and physical information in a nonimaging mode was resolved
      at approximately 10 nm. Grazing vs direct impacts on NPs were identified and
      quantified. NP fragmentation from direct impacts with Au(400)(4+) and C(60)(+)
      was observed for the first time.

PMID- 19105606
TI  - Ion exchange resins: catalyst recovery and recycle.

PMID- 19105607
TI  - Versatile method for chiral recognition by the quartz crystal microbalance:
      chiral mandelic acid as the detection model.
AB  - Chiral recognition is considered to be the most important, fundamental basis in
      the development of separation technology for chiral isomers in the pharmaceutical
      and biotechnology fields. However, the selective detection of individual
      enantiomers is still one of the most difficult analytical tasks because of the
      close similarity of the molecular configurations between chiral isomers. This
      study presents a versatile vapor-diffused molecular assembly (VDMA) reaction
      approach for chiral recognition by the quartz crystal microbalance (QCM). Chiral
      L/D-mandelic acid (MA) was used as the detection model, and L-phenylalanine (L
      Phe) was used as the selector. The construction of the L-Phe-modified QCM sensor
      involved a four-step layer-by-layer assembly procedure. Each modification step
      was analyzed by cyclic voltammetry, the contact angle, and a resonance frequency
      measurement. The chiral recognizability of the L-Phe-modified QCM sensor to L
      mandelic acid was then examined by resonance frequency measurement using the
      novel VDMA technique and also investigated by atomic force microscope (AFM)
      measurements. A chiral discrimination factor of up to approximately 9 between L-
      and d-MA on the L-Phe-modified QCM sensor was obtained by using this gaseous
      phase reaction technique. AFM results also showed obvious selective aggregation
      of L-MA on the L-Phe-modified surface but no noticeable aggregation of D-MA
      during the VDMA reaction. Both of the QCM and AFM results confirmed the
      usefulness of this proposed VDMA technique for the study of chiral recognition.
      The main advantage of the proposed method is that it offers a universal simple
      application scheme for the QCM detection of small resonance frequency changes due
      to chiral molecular recognition by a chiral selector immobilized on the QCM
      sensor surface.

PMID- 19105608
TI  - Differential potencies of naturally occurring regioisomers of nitrolinoleic acid
      in PPARgamma activation.
AB  - Previous studies demonstrated that the naturally occurring electrophile and
      PPARgamma ligand, nitrolinoleic acid (NO(2)-LA), exists as a mixture of four
      regioisomers [Alexander, R. L., et al. (2006) Biochemistry 45, 7889-7896]. We
      hypothesized that these alternative isomers have distinct bioactivities;
      therefore, to determine if the regioisomers are quantitatively or qualitatively
      different with respect to PPARgamma activation, NO(2)-LA was separated into three
      fractions which were identified by NMR (13-NO(2)-LA, 12-NO(2)-LA, and a mixture
      of 9- and 10-NO(2)-LA) and characterized for PPARgamma interactions. A
      competition radioligand binding assay showed that all three NO(2)-LA fractions
      had similar binding affinities for PPARgamma (IC(50) = 0.41-0.60 microM) that
      were comparable to that of the pharmaceutical ligand, rosiglitazone (IC(50) =
      0.25 microM). However, when PPARgamma-dependent transcription activation was
      examined, there were significant differences observed among the NO(2)-LA
      fractions. Each isomer behaved as a partial agonist in this reporter gene assay;
      however, the 12-NO(2) derivative was the most potent with respect to maximum
      activation of PPARgamma and an EC(50) of 0.045 microM (compare with the
      rosiglitazone EC(50) of 0.067 microM), while the 13-NO(2) and 9- and 10-NO(2)
      derivatives were considerably less effective with EC(50) values of 0.41-0.62
      microM. We conclude that the regioisomers of NO(2)-LA are not functionally
      equivalent. The 12-NO(2) derivative appears to be the most potent in PPARgamma
      dependent transcription activation, whereas the weaker PPARgamma agonists, 13
      NO(2) and 9- and 10-NO(2), may be relatively more important in signaling via
      other, PPARgamma-independent pathways in which this family of nitrolipid
      electrophiles is implicated.

PMID- 19105609
TI  - Proteome analysis of bronchoalveolar lavage in individuals from Metsovo,
      nonoccupationally exposed to asbestos.
AB  - Inhabitants of Metsovo, NW Greece, have been exposed to an asbestos whitewash,
      resulting in malignant pleural mesothelioma (MPM) and pleural calcifications
      (PCs). Interestingly, those with PCs (PC(+)) are less prone to MPM. They also
      have lymphocytic alveolitis, and differences in bronchoalveolar lavage (BAL)
      proteins, compared with those without pleural calcifications (PC(-)). This may
      mean a different response to the fiber leading to different susceptibility to
      neoplasia. To further evaluate this, a proteomic analysis of BAL proteins was
      performed. Proteomic analysis (2D-electrophoresis/Mass Spectrometry) of BAL in
      Metsovites nonoccupationally exposed to asbestos revealed increased albumin
      fragments, alpha1-antitrypsin, S100-A9 and HSP27, suggesting ongoing
      inflammation. In those without pleural calcifications, increased expression of
      acid ceramidase, glutathione-S-transferase and presence of calcyphosin, all
      involved in cell cycle regulation and death as well as in the detoxification of
      mutagenic and toxic agents, lend further support to our thesis of possible
      "protection against neoplasia" in Metsovites with pleural calcifications.

PMID- 19105610
TI  - New era dawns for US stem cell research.

PMID- 19105611
TI  - Induced pluripotent stem cells from adult testis: a new source of stem cells?

PMID- 19105615
TI  - Hemangioblasts from human embryonic stem cells generate multilayered blood
      vessels with functional smooth muscle cells.
AB  - BACKGROUND: The formation and regeneration of functional vasculatures require
      both endothelial cells (ECs) and vascular smooth muscle cells (SMCs).
      Identification and isolation of progenitors with potential for both EC and SMC
      lineage differentiation from an inexhaustible source, such as human embryonic
      stem (hES) or induced pluripotent stem cells, will be desirable for cell
      replacement therapy. METHOD: Recently, we have developed a serum-free and animal
      feeder-free differentiation system to generate blast cells (BCs) from hESCs.
      These cells possess the characteristics of hemangioblasts in vitro and are
      capable of repairing damaged retinal vasculatures, restoring blood flow in hind
      limb ischemia and reducing the mortality rate after myocardial infarction in
      vivo. We demonstrate here that BCs express markers of SMCs and differentiate into
      smooth muscle-like cells (SMLCs), in addition to ECs and hematopoietic cells.
      RESULTS: When BCs from individual blast colonies were cultured in SMC medium,
      they differentiated into both ECs and SMLCs, which formed capillary-vascular-like
      structures after replating on Matrigeltrade mark. The SMLCs expressed SMC
      specific markers (alpha-SM actin and calponin) and contracted upon treatment with
      carbachol. When implanted in nude mice, these cells formed microvasculature with
      ECs in Matrigel plaques. The BCs differentiated into both ECs and SMLCs, and
      incorporated into blood vessels after injection into ischemic tissue. CONCLUSION:
      These results demonstrate that hemangioblasts (BCs) generated from hESCs are
      tripotential and can provide a potentially inexhaustible source of cells for the
      treatment of human blood and vascular diseases.

PMID- 19105616
TI  - The effect of delivery via narrow-bore needles on mesenchymal cells.
AB  - AIMS: Recently, there have been numerous preclinical and human studies
      investigating the regenerative capacity of cell suspensions following their
      direct injection into a target organ: the fundamental parameters for successful
      (clinical) cell therapy. At present, limited data exist in the identification of
      factors important for the survival of these cells (i.e., morphology, viability
      and proliferation rates) during and following their ejection via narrow-bore
      needles. MATERIALS & METHODS: Primary murine mesenchymal stem cells (mMSCs) were
      isolated, expanded and processed into a concentrated cell suspension consisting
      of either HBSS or HBSS supplemented with the antioxidant n-acetyl-cysteine. This
      suspension was then ejected from a 10 microl Hamilton syringe, via a variety of
      bore-sized needles, at different ejection rates. Cell characteristics including
      viability, spreading and attachment, apoptosis and proliferative ability were
      then assessed. RESULTS: Following manipulation within a syringe, a decrease in
      the viability and cell spreading of mMSCs and a concurrent increase in the
      production of the caspase-3 protein, an early regulatory event in apoptosis,
      occurs. These detrimental effects were found to be increased when the cells were
      left in the syringe chamber for increased periods of time, and were similar at 5
      microl/min and 1 microl/min ejection rates. However, on increasing the needle
      bore diameter, a significant reduction in these characteristics was observed. By
      comparison, mMSCs that were left to stand at room temperature (18-20 degrees C),
      but were not manipulated within a syringe, showed a significantly greater
      viability compared with manipulated cells. However, cells kept at 4 degrees C
      demonstrated a decreased viability compared with manipulated cells. When the mMSC
      were incubated with n-acetyl-cysteine, a known antioxidant, no significant change
      in caspase-3 production or cell spreading was observed. CONCLUSIONS: This study
      highlights potential parameters, such as minimizing the time period the cells are
      within the syringe and the use of wider-bore needles, involved in maintaining the
      high viable cell density required for the delivery of cell suspensions for cell
      therapy applications.

PMID- 19105618
TI  - Cells and biomaterials in cartilage tissue engineering.
AB  - Cartilage defects are notoriously difficult to repair and owing to the long-term
      prognosis of osteoarthritis, and a rapidly aging population, a need for new
      therapies is pressing. Cell-based therapies for cartilage regeneration were
      introduced into patients in the early 1990s. Since that time the technology has
      developed from a simple cell suspension to more complex 3D structures. Cells,
      both chondrocytes and stem cells, have been incorporated into scaffold material
      with the aim to better recreate the natural environment of the cell, while
      providing more structural support to withstand the large forces applied on the de
      novo tissue. This review aims to provide an overview of potential cell sources
      and different scaffold materials, which are in development for cartilage tissue
      engineering.

PMID- 19105619
TI  - Genetically engineered mesenchymal stem cells: applications in spine therapy.
AB  - Spine disorders and intervertebral disc degeneration are considered the main
      causes for the clinical condition commonly known as back pain. Spinal fusion by
      implanting autologous bone to produce bony bridging between the two vertebrae
      flanking the degenerated-intervertebral disc is currently the most efficient
      treatment for relieving the symptoms of back pain. However, donor-site morbidity,
      complications and the long healing time limit the success of this approach. Novel
      developments undertaken by regenerative medicine might bring more efficient and
      available treatments. Here we discuss the pros and cons of utilizing genetically
      engineered mesenchymal stem cells for inducing spinal fusion. The combination of
      the stem cells, gene and carrier are crucial elements for achieving optimal
      spinal fusion in both small and large animal models, which hopefully will lead to
      the development of clinical applications.

PMID- 19105617
TI  - Update on therapeutic vascularization strategies.
AB  - The ability to exploit angiogenesis and vascularization as a therapeutic strategy
      will be of enormous benefit to a wide range of medical and tissue-engineering
      applications. Angiogenic growth factor and cell-based therapies have thus far
      failed to produce a robust healing response in clinical trials for a variety of
      ischemic diseases, while engineered tissue substitutes are still size-limited by
      a lack of vascularization. The purpose of this review is to investigate current
      research advances in therapeutic vascularization strategies applied to ischemic
      disease states, tissue engineering and regenerative medicine. Recent advances are
      discussed that focus on better regulation of growth factor delivery and attempts
      to better mimic natural processes by delivering combinations of multiple growth
      factors, cells and bioactive materials in the right spatial and temporal setting.
      Some unconventional approaches and novel therapeutic targets that hold
      significant potential are also discussed.

PMID- 19105620
TI  - Adipose-derived stem cells for soft tissue reconstruction.
AB  - In soft tissue repair, there are several surgical options such as nondegradable,
      inert, synthetic, biodegradable implants or autologous tissue transplantation.
      However, the potential of using autologous adult stem cells derived from fat
      tissue is quickly becoming a clinical reality. The possibility of using an
      abundant source of extraneous tissue as a soft tissue implant has significant
      implications for plastic and reconstructive surgeons. This strategy would be
      particularly useful after tumor removal or trauma. The ability of adult stem
      cells derived from adipose tissue (termed adipose-derived stem cell) to
      proliferate and differentiate in vivo or in vitro is actively being studied owing
      to the potential implementation in reconstructive surgery. This review describes
      innovative research strategies and discusses the first clinical studies involving
      adipose-derived stem cells as a motif for soft tissue reconstruction.

PMID- 19105621
TI  - Autologous bone marrow-derived stem cells for ischemic heart failure: REGENERATE
      IHD trial.
AB  - The field of autologous stem/progenitor cell transplantation for cardiovascular
      diseases has moved rapidly from basic science research to clinical trials. To
      date, only a handful of pilot studies have reported the use of this novel
      strategy for heart failure patients. Most of these studies have demonstrated
      encouraging safety and efficacy data. However, this will need to be validated in
      large, randomized trials. Here, we introduce the ongoing REGENERATE-IHD trial,
      which is the largest randomized, placebo-controlled trial in the UK investigating
      the use of granulocyte-colony stimulating factor and autologous bone marrow
      derived stem/progenitor cells to improve cardiac function and symptoms in heart
      failure patients.

PMID- 19105622
TI  - The 2nd International Collaborative Symposium on Stem Cell Research.
AB  - The Second Biennial International Collaborative Symposium on Stem Cell Research,
      held in Seoul, Korea, on 18-19 September 2008, showcased talks by a roster of
      established and emerging leaders in stem cell biology, and demonstrated how far
      and fast the field has moved in the last 2 years.

PMID- 19105623
TI  - Stem cells Europe 2008.
AB  - The focus of this conference report is to highlight some of the key themes
      presented at this excellent annual conference hosted by Select Biosciences Ltd at
      the Hilton Amsterdam, which attracted a worldwide audience of more than 150
      delegates. This 3-day conference comprised 2 days of presentations in the
      'Research Track' and 1 day of presentations in the 'Business/Commercialization
      Track'. The research track of this conference focused on the following key
      topics: basic research in the stem cells space; understanding stem cell biology;
      pluripotency; characterization of different types of stem cells and their role in
      mediating regenerative medicine; stem cells in drug discovery and development
      activities; and cancer stem cells. The business/commercialization track of the
      conference focused on the following key topics: case studies of companies
      commercializing stem cells; and stem cell patentability in the USA, EU and the
      UK.

PMID- 19105625
TI  - A two-dose regimen of a vaccine against type III secreted proteins reduced
      Escherichia coli O157:H7 colonization of the terminal rectum in beef cattle in
      commercial feedlots.
AB  - A large-scale clinical vaccine trial of commercially fed cattle was conducted to
      test the efficacy of a two-dose regimen of a vaccine product against type III
      secreted proteins of enterohemorrhagic Escherichia coli O157:H7 on the
      probability to detect the same organism from terminal rectal mucosa (TRM) as a
      measure of gut colonization. Vaccine was administered to all cattle within
      treated pens at arrival processing and at reimplant processing. At harvest, TRM
      was collected from a sample of cattle from within vaccinated and nonvaccinated
      pens. The TRM were collected by scraping the mucosa of the terminal rectum 3-5 cm
      proximal to the rectoanal juncture. E. coli O157:H7 was isolated and identified
      from TRM using standard culture methods involving selective enrichment,
      immunomagnetic separation, and PCR confirmation. The probability to detect E.
      coli O157:H7 from TRM was modeled using a generalized linear mixed model with a
      logit link function and accounting for random effects of pen within feedlot.
      Seven hundred eighteen cattle were tested from within 21 pens of cattle (11
      vaccinated and 10 not vaccinated) representing 3683 cattle. E. coli O157:H7 was
      cultured from 68 of 718 (9.5%) TRM samples. Eleven of 382 (2.9%) vaccinated
      cattle and 57 of 336 (17.0%) nonvaccinated cattle were TRM culture positive. From
      the multilevel logistic model, vaccinated cattle were 92% less likely to be
      colonized with E. coli O157:H7 than nonvaccinated cattle (odds ratio [OR] = 0.07,
      p = 0.0008). Additional explanatory variables were region of the state (OR = 7.4,
      p = 0.04), and pens with fewer cattle (OR = 0.22, p = 0.05). We concluded that
      the two-dose vaccine regimen effectively reduced the probability for E. coli
      O157:H7 colonization of the terminal rectum of commercially fed cattle at
      harvest.

PMID- 19105626
TI  - STD-NMR used to elucidate the fine binding specificity of pathogenic anti
      ganglioside antibodies directly in patient serum.
AB  - High-resolution binding profiles were elucidated for anti-GM1 IgM autoantibodies
      from two patients with a progressive form of paraproteinemic polyneuropathy.
      Antibody-ligand interaction was characterized by generating STD-NMR signals in
      target ganglio-oligosaccharides added directly to patient sera, without the
      requirement of antibody fractionation. Both immunoglobulins were found to have
      similar binding modalities, with interaction confined to two distinct spatially
      separated regions of GM1: the terminal betaGal(1-3)betaGalNAc disaccharide unit
      and the sialic acid residue. We describe a unique and powerful biophysical
      technique applied to define the molecular interaction between autoimmune disease
      causing antibodies and their ganglioside targets.

PMID- 19105627
TI  - Competitive exclusion Escherichia coli cultures on E. coli O157 growth in batch
      culture ruminal or fecal microbial fermentation.
AB  - The purpose of this study was to determine the efficacy of competitive exclusion
      (CE) Escherichia coli cultures (ATCC 202018 and 202019) for reducing E. coli O157
      in batch culture fermentations with ruminal or fecal microbial inoculum derived
      from a cannulated feedlot steer fed a corn-grain-based, high-grain diet. A non-CE
      (NCE) E. coli strain (ATCC 25922) was included as a control. Anaerobic
      fermentations (50 mL) were set up in serum bottles with a 2:1 mineral buffer to
      microbial inoculum ratio and with or without gluconic acid, a component of
      intestinal mucus, which has been shown to be stimulatory to the growth of E. coli
      O157 in vitro. A five-strain mixture of E. coli O157 made resistant to nalidixic
      acid (50 microg/mL; Nal(R)) was added to each fermentation, and concentrations of
      Nal(R) E. coli O157 were determined after 0, 6, 12, and 24 h of fermentation. In
      ruminal microbial fermentation, the CE treatment had a lower (0.6 log; p < 0.01)
      concentration of Nal(R) E. coli O157 than the NCE control at 24 h, regardless of
      gluconic acid inclusion. In fecal microbial fermentation, the CE treatment did
      not affect Nal(R) E. coli O157 concentrations in fermentations without gluconic
      acid; but with gluconic acid inclusion, Nal(R) E. coli O157 concentrations were
      lower in the CE treatment than in NCE controls at 12 h (1.7 log CFU/mL lower) and
      24 h (1.9 log CFU/mL lower). In vitro fermentation with ruminal or fecal
      microbial inoculum could be a simple and inexpensive initial approach to assess
      efficacy of CE cultures for reducing E. coli O157.

PMID- 19105628
TI  - Fabrication of substrate-independent protein microarrays using polyelectrolyte
      scaffolding.
AB  - While significant advances have been made in regard to protein microarray surface
      chemistries, the surface modification strategies developed are generally
      substrate-specific and cannot be interchanged between different materials and
      platforms. This current lack of substrate-independent surface modification
      strategies makes it difficult to compare or transfer fabrication methodologies
      between dissimilar substrates. To address this shortcoming, we have developed an
      interchangeable surface scaffold, which can be utilized to fabricate protein
      microarrays on a variety of materials with nearly identical results. The surface
      scaffold is deposited by alternate electrostatic assembly of the cationic and
      anionic polyelectrolytes poly(allylamine hydrochloride) and poly(sodium 4
      styrenesulfonate), respectively. Once assembled, the polyelectrolyte scaffold
      serves to mask the underlying surface properties of different materials and
      convert them to the surface properties of the scaffold itself. By obtaining
      common surface properties across different materials, it is possible to eliminate
      differences in protein surface density, spot diameter, and nonspecific binding of
      analytes on substrates as diverse as glass, gold, mica, silicon, and polymer. The
      concept of substrate-independent polyelectrolyte scaffolding described here
      provides researchers with a powerful new tool that can be utilized to compare,
      optimize, and transfer useful protein microarray surface chemistries across
      different materials and platforms.

PMID- 19105629
TI  - Dimer disruption and monomer sequestration by alkyl tripeptides are successful
      strategies for inhibiting wild-type and multidrug-resistant mutated HIV-1
      proteases.
AB  - Wild-type and drug-resistant mutated HIV-1 proteases are active as dimers. This
      work describes the inhibition of their dimerization by a new series of alkyl
      tripeptides that target the four-stranded antiparallel beta-sheet formed by the
      interdigitation of the N- and C-monomer ends of each monomer. Analytical
      ultracentrifugation was used to give experimental evidence of their mode of
      action that is disruption of the active homodimer with formation of inactive
      monomer-inhibitor complexes. The minimum length of the alkyl chain needed to
      inhibit dimerization was established. Sequence variations led to a most potent
      HIV-PR dimerization inhibitor: palmitoyl-Leu-Glu-Tyr (Kid = 0.3 nM). Insertion of
      d-amino acids at the first two positions of the peptide moiety increased the
      inhibitor resistance to proteolysis without abolishing the inhibitory effect.
      Molecular dynamics simulations of the inhibitor series complexed with wild-type
      and mutated HIV-PR monomers corroborated the kinetic data. They suggested that
      the lipopeptide peptide moiety replaces the middle strand in the highly conserved
      intermolecular four-stranded beta-sheet formed by the peptide termini of each
      monomer, and the alkyl chain is tightly grasped by the active site groove capped
      by the beta-hairpin flap in a "superclosed" conformation. These new inhibitors
      were equally active in vitro against both wild-type and drug-resistant
      multimutated proteases, and the model suggested that the mutations in the monomer
      did not interfere with the inhibitor.

PMID- 19105630
TI  - Proteomic analysis and identification of the structural and regulatory proteins
      of the Rhodobacter capsulatus gene transfer agent.
AB  - The gene transfer agent of Rhodobacter capsulatus (GTA) is a unique phage-like
      particle that exchanges genetic information between members of this same species
      of bacterium. Besides being an excellent tool for genetic mapping, the GTA has a
      number of advantages for biotechnological and nanoengineering purposes. To
      facilitate the GTA purification and identify the proteins involved in GTA
      expression, assembly and regulation, in the present work we construct and
      transform into R. capsulatus Y262 a gene coding for a C-terminally His-tagged
      capsid protein. The constructed protein was expressed in the cells, assembled
      into chimeric GTA particles inside the cells and excreted from the cells into
      surrounding medium. Transmission electron micrographs of phosphotungstate
      stained, NiNTA-purified chimeric GTA confirm that its structure is similar to
      normal GTA particles, with many particles composed both of a head and a tail. The
      mass spectrometric proteomic analysis of polypeptides present in the GTA
      recovered outside the cells shows that GTA is composed of at least 9 proteins
      represented in the GTA gene cluster including proteins coded for by Orf's 3, 5, 6
      9, 11, 13, and 15.

PMID- 19105631
TI  - Rapid measurement and prediction of bacterial contamination in milk using an
      oxygen electrode.
AB  - An oxygen electrode was used to measure oxygen consumption to determine bacterial
      contamination in milk. Dissolved oxygen (DO) measured at 10-35 degrees C for 2
      hours provided a reasonable prediction efficiency (r > or = 0.90) of the amount
      of bacteria between 1.9 and 7.3 log (CFU/mL). A temperature-dependent predictive
      model was developed that has the same prediction accuracy like the normal
      predictive model. The analysis performed with and without stirring provided the
      same prediction efficiency, with correlation coefficient of 0.90. The measurement
      of DO is a simple and rapid method for the determination of bacteria in milk.

PMID- 19105632
TI  - Proteomic investigation of phosphorylation sites in poly(ADP-ribose) polymerase-1
      and poly(ADP-ribose) glycohydrolase.
AB  - Phosphorylation is a very common post-translational modification event known to
      modulate a wide range of biological responses. Beyond the regulation of protein
      activity, the interrelation of phosphorylation with other post-translational
      mechanisms is responsible for the control of diverse signaling pathways. Several
      observations suggest that phosphorylation of poly(ADP-ribose) polymerase-1 (PARP
      1) regulates its activity. There is also accumulating evidence to suggest the
      establishment of phosphorylation-dependent assembly of PARP-1-associated
      multiprotein complexes. Although it is relatively straightforward to demonstrate
      phosphorylation of a defined target, identification of the actual amino acids
      involved still represents a technical challenge for many laboratories. With the
      use of a combination of bioinformatics-based predictions tools for generic and
      kinase-specific phosphorylation sites, in vitro phosphorylation assays and mass
      spectrometry analysis, we investigated the phosphorylation profile of PARP-1 and
      poly(ADP-ribose) glycohydrolase (PARG), two major enzymes responsible for
      poly(ADP-ribose) turnover. Mass spectrometry analysis revealed the
      phosphorylation of several serine/threonine residues within important regulatory
      domains and motifs of both enzymes. With the use of in vivo microirradiation
      induced DNA damage, we show that altered phosphorylation at specific sites can
      modify the dynamics of assembly and disassembly of PARP-1 at sites of DNA damage.
      By documenting and annotating a collection of known and newly identified
      phosphorylation sites, this targeted proteomics study significantly advances our
      understanding of the roles of phosphorylation in the regulation of PARP-1 and
      PARG.

PMID- 19105633
TI  - Systematic identification of genetic loci required for polymyxin resistance in
      Campylobacter jejuni using an efficient in vivo transposon mutagenesis system.
AB  - The aim of this study was to identify genetic loci required for polymyxin (PM)
      resistance in Campylobacter jejuni using an efficient in vivo random mutagenesis
      system. PM has been widely used as a model peptide to examine mechanisms of
      bacterial resistance to antimicrobial peptides (AMPs), the major effectors of
      host innate immunity and also candidates for a new generation of antibiotics. In
      this study, a commercially available transposon mutagenesis approach (EZ-Tn5 <KAN
      2> Transposome; Epicentre, Madison, WI) was evaluated and used to systematically
      identify Campylobacter mutants with increased susceptibility to PM. This simple,
      yet efficient, transposon mutagenesis approach identified 12 mutants representing
      seven different genes of C. jejuni 81-176 involved in acquired PM resistance.
      Backcrossing of the transposon mutations into the parent strain confirmed that
      the PM-sensitive phenotype in each mutant was linked to the gene with a specific
      transposon insertion. The genes are identified as being involved in the synthesis
      of cell-surface carbohydrates, modification of intracellular targets, signal
      transduction, and modulation of transmembrane potential. The mutant with the
      highest susceptibility to PM contains a transposon insertion in a putative galU
      gene that is essential for production of uridine diphosphate glucose (UDP)
      glucose, a precursor required for lipooligosaccharide (LOS) synthesis. LOS
      analysis by tricine SDSPAGE showed significant truncation of the LOS core
      structure in the galU mutant. Susceptibility assays also indicated that GalU
      contributed C. jejuni resistance to some natural AMPs. Complementation of the
      galU mutant in trans fully restored LOS synthesis and resistance to the levels of
      the parent strain. Together, these results define seven C. jejuni genetic loci
      that will be useful for characterizing the molecular basis of Campylobacter
      resistance to PM and natural AMPs, and also highlight the usefulness of the in
      vivo mutagenesis approach for systematic characterization of functionally
      important Campylobacter genes.

PMID- 19105635
TI  - Pathogen prevalence and influence of composted dairy manure application on
      antimicrobial resistance profiles of commensal soil bacteria.
AB  - Composting manure, if done properly, should kill pathogenic bacteria such as
      Salmonella and Escherichia coli O157:H7, providing for an environmentally safe
      product. Over a 3-year period, samples of composted dairy manure, representing 11
      composting operations (two to six samples per producer; 100 total samples), were
      screened for Salmonella and E. coli O157:H7 and were all culture negative.
      Nonpathogenic bacteria were cultured from these compost samples that could
      theoretically facilitate the spread of antimicrobial resistance from the dairy to
      compost application sites. Therefore, we collected soil samples (three samples
      per plot; 10 plots/treatment; 90 total samples) from rangeland that received
      either composted dairy manure (CP), commercial fertilizer (F), or no treatment
      (control, CON). Two collections were made appoximately 2 and 7 months following
      treatment application. Soil samples were cultured for Pseudomonas and
      Enterobacter and confirmed isolates subjected to antimicrobial susceptibility
      testing. Three species of Enterobacter (cloacae, 27 isolates; aeroginosa, two
      isolates; sakazakii, one isolate) and two species of Pseudomonas (aeruginosa, 11
      isolates; putida, seven isolates) were identified. Five Enterobacter isolates
      were resistant to ampicillin and one isolate was resistant to spectinomycin. All
      Pseudomonas isolates were resistant to ampicillin, ceftiofur, florfenicol,
      sulphachloropyridazine, sulphadimethoxine, and trimethoprim/sulfamethoxazole and
      most isolates were resistant to chlortetracycline and spectinomycin. Pseudomonas
      isolates were resistant to an average of 8.6, 7.9, and 8 antibiotics for CON, CP,
      and F treatments, respectively. No treatment differences were observed in
      antimicrobial resistance patterns in any of the soil isolates examined. Results
      reported herein support the use of composted dairy manure as an environmentally
      friendly soil amendment.

PMID- 19105634
TI  - Reconstitution of Escherichia coli glutamine synthetase adenylyltransferase from
      N-terminal and C-terminal fragments of the enzyme.
AB  - ATase brings about the short-term regulation of glutamine synthetase (GS) by
      catalyzing the adenylylation and deadenylylation of GS in response to signals of
      cellular nitrogen status and energy. The adenylyltransferase (AT) activity of
      ATase is activated by glutamine and by the unmodified form of the PII signal
      transduction protein and is inhibited by PII-UMP. Conversely, the adenylyl
      removing (AR) activity of ATase is activated by PII-UMP and inhibited by
      unmodified PII and by glutamine. Here, we show that the enzyme can be
      reconstituted from two purified polypeptides that comprise the N-terminal two
      thirds of the protein and the C-terminal one-third of the protein. Properties of
      the reconstituted enzyme support recent hypotheses for the sites of regulatory
      interactions and mechanisms for intramolecular signal transduction. Specifically,
      our results are consistent with the protein activators (PII and PII-UMP) binding
      to the enzyme domain with the opposing activity, with intramolecular signal
      transduction by direct interactions between the N-terminal AR catalytic domain
      and the C-terminal AT catalytic domain. Similarly, glutamine inhibition of the AR
      activity involved intramolecular signaling between the AT and AR domains.
      Finally, our results are consistent with the hypothesis that the AR activity of
      the N-terminal domain required activation by the opposing C-terminal (AT) domain.

PMID- 19105636
TI  - Synthesis and C-alkylation of hindered aldehyde enamines.
AB  - A new reactivity mode of hindered lithium amides with terminal epoxides is
      described whereby aldehyde enamines are produced via a previously unrecognized
      reaction pathway. Some of these aldehyde enamines display unprecedented C
      alkylation reactivity toward unactivated primary and secondary alkyl halides. For
      comparison, the reactivity of aldehyde enamines synthesized via a traditional
      condensation method was examined. C- rather than N-alkylation was the dominant
      reaction pathway found with a range of electrophiles, making this route to alpha
      alkylated aldehydes more synthetically useful than previously reported.

PMID- 19105637
TI  - Synthesis of four novel natural product inspired scaffolds for drug discovery.
AB  - Inspired by the novel spiro structures of a number of bioactive natural products
      such as the histrionicotoxins, a series of novel spiro scaffolds have been
      designed and robust syntheses developed. The scaffolds are ready-to-use building
      blocks and can be easily prepared on a 5-20 g scale. They contain two amino
      groups (one Boc-protected) and have been designed for ease of conversion to a
      lead generation library, using either amide formation or reductive amination
      procedures. The synthesis of the 1,9-diazaspiro[5.5]undecane and 3,7
      diazaspiro[5.6]dodecane ring systems was achieved using RCM as the key step. A
      simple workup procedure is reported for the removal of highly colored ruthenium
      residues. The synthesis of the 1,8-diazaspiro[4.5]decane scaffold has been
      achieved using a bromine-mediated 5-endo cyclization of the corresponding 4
      aminobutene intermediate under acidic conditions. This is the first example of
      this type of cyclization to be reported. A novel mechanism involving a bromine
      transfer reaction from an initially formed bromonium ion to a neighboring
      nitrogen atom is suggested as the reason for the failure of this type of reaction
      under "normal" bromination conditions. An unusual rearrangement of a 1-acyl-1,9
      diazaspiro[5.5]undecane to the corresponding 9-acyl-1,9-diazaspiro[5.5]undecane
      is reported.

PMID- 19105638
TI  - Competition studies in alkyne electrophilic cyclization reactions.
AB  - The relative reactivity of various functional groups toward alkyne electrophilic
      cyclization reactions has been studied. The required diarylalkynes have been
      prepared by consecutive Sonogashira reactions of appropriately substituted aryl
      halides and competitive cyclizations have been performed using I(2), ICl, NBS and
      PhSeCl as electrophiles. The results indicate that the nucleophilicity of the
      competing functional groups, polarization of the alkyne triple bond, and the
      cationic nature of the intermediate are the most important factors in determining
      the outcome of these reactions.

PMID- 19105639
TI  - Sampling and analytical variability associated with the determination of total
      aflatoxins and ochratoxin A in powdered ginger sold as a dietary supplement in
      capsules.
AB  - The U.S. Food and Drug Administration is studying the need to monitor dietary
      supplements for mycotoxins such as total aflatoxins and ochratoxin A. An
      effective mycotoxin-monitoring program requires knowledge of the sampling and
      analytical variability associated with the determination of total aflatoxins (AF)
      and ochratoxin A (OTA) in dietary supplements. Three lots of ginger sold as a
      powder in capsule form and packaged in individual bottles were analyzed for both
      AF and OTA. The total variability associated with measuring AF and OTA in
      powdered ginger was partitioned into bottle-to-bottle, within bottle, and
      analytical variances. The variances were estimated using a nested design. For AF
      and OTA, the within-bottle variance associated with the 5 g laboratory sample
      size was the largest component of variability accounting for about 43% and 85% of
      the total variance, respectively; the analytical variance accounted for about 34%
      and 9% of the total variability, respectively; and the bottle-to-bottle variance
      accounted for about 23% and 7% of the total variance, respectively. When the
      total variance is converted into the coefficient of variation (CV or standard
      deviation relative to the mean concentration), the CV is lower for AF (16.9%)
      than OTA (24.7%).

PMID- 19105640
TI  - Event-specific detection of stacked genetically modified maize Bt11 x GA21 by UP
      M-PCR and real-time PCR.
AB  - More and more stacked GMOs have been developed for more improved functional
      properties and/or a stronger intended characteristic, such as antipest, improved
      product efficiency etc. Bt11 x GA21 is a new kind of stacked GM maize developed
      by Monsanto Company. Since there are no unique flanking sequences in stacked
      GMOs, up to now, no appropriate method has been reported to accurately detect
      them. In this passage, a novel universal primer multiplex PCR (UP-M-PCR) was
      developed and applied as a rapid screening method for the simultaneous detection
      of five target sequences (NOS, 35S, Bt11 event, GA21 event, and IVR) in maize
      Bt11 x GA21. This method overcame the disadvantages rooted deeply in conventional
      multiplex PCR such as complex manipulation, lower sensitivity, self-inhibition
      and amplification disparity resulting from different primers. What's more, it got
      a high specificity and had a detection limit of 0.1% (approximates to 38 haploid
      genome copies). Furthermore, real-time PCR combined with multivariate statistical
      analysis was used for accurate quantification of stacked GM maize Bt11 x GA21 in
      100% GM maize mixture (Bt11 x GA21, Bt11 and GA21). Detection results showed that
      this method could accurately validate the content of Bt11, GA21 and Bt11 x GA21
      in 100% GM mixture with a detection limit of 0.5% (approximates to 200 haploid
      genome copies) and a low relative standard deviation <5%. All the data proved
      that this method may be widely applied in event-specific detection of other
      stacked GMOs in GM-mixture.

PMID- 19105641
TI  - Simulation study of protein-mediated vesicle fusion.
AB  - A dissipative particle dynamics simulation method is used to probe the mechanism
      of protein-mediated membrane fusion. The coarse-grained models for proteins are
      designed based on the function of fusion proteins. Attractive forces have been
      introduced to produce a protein complex. The formation of protein complexes
      provides mechanical forces to bring membranes in proximity and trigger their
      merging. The whole fusion process is in good agreement with the scaffold
      hypothesis. Additionally, if self-defined interactions are also imposed on
      transmembrane segments (TMSs), their association will yield an unstable fusion
      pore, which can incorporate lipid and water to accomplish membrane fusion. It
      indicates the formation of a protein-lined pore will promote the stalk-pore
      transition and accelerate the fusion process.

PMID- 19105642
TI  - Grape variety effect on proanthocyanidin composition and sensory perception of
      skin and seed tannin extracts from bordeaux wine grapes (Cabernet Sauvignon and
      Merlot) for two consecutive vintages (2006 and 2007).
AB  - Grape variety [Cabernet Sauvignon (CS) and Merlot (M)] effect on the
      proanthocyanidin composition and sensory perception of wine grapes from Bordeaux
      vineyards for two successive vintages (2006 and 2007) is reported. The flavan-3
      ol monomers [(+)-catechin = C, (-)-epicatechin = EC, (-)-epicatechin-O-gallatte =
      ECG] and the proanthocyanidin oligomers [dimers B1, B2, B3, and B4 and trimer Cat
      Cat-Epi (T)] in grape seed and skin tannin extracts were identified and
      quantified at harvest. Proanthocyanidin subunit compositions, percentage of
      galloylation (%G), and percentage of prodelphinidins (%P) as well as mean degree
      of polymerization (mDP) of the proanthocyanidin fraction were determined. Sensory
      analysis concerning the astringency and bitterness intensity of the
      proanthocyanidins of skin and seed tannin extracts was also performed. The
      results showed that proanthocyanidin composition can be greatly affected by grape
      variety. For both vintages between CS and M, significant differences were found
      on mDP (p < 0.05) in seed tannin extracts, whereas in skin tannin extracts,
      significant differences were observed for %G and %P (p < 0.05). Sensory analysis
      showed that grape variety influenced neither astringency nor bitterness intensity
      perception for both skin and seed tannin extracts for the two successive vintages
      studied. A positive correlation was found between astringency intensity, mDP, and
      B3 content in skin tannin extracts.

PMID- 19105644
TI  - Modification of the health-promoting value of potato tubers field grown under
      drought stress: emphasis on dietary antioxidant and glycoalkaloid contents in
      five native andean cultivars (Solanum tuberosum L.).
AB  - The effects of drought stress on dietary antioxidant and glycoalkaloid contents
      in potato tubers were investigated using a selection of five native Andean
      cultivars. Both freshly harvested and 4 month-stored tubers were analyzed.
      Responses to drought stress were highly cultivar-specific. The antioxidant
      contents of the yellow tuber-bearing cultivars (Sipancachi and SS-2613) were
      weakly affected by the drought treatment, whereas the pigmented cultivars
      demonstrated highly cultivar-dependent variations. A drastic reduction of
      anthocyanins and other polyphenols was revealed in the red- (Sullu) and purple
      fleshed (Guincho Negra) cultivars, whereas an increase was shown in the purple
      skinned and yellow-fleshed cultivar (Huata Colorada). The hydrophilic antioxidant
      capacity (evaluated by Folin-Ciocalteu and H-oxygen radical absorbance capacity
      assays) was highly correlated with the polyphenol content and followed,
      therefore, the same behavior upon drought. Carotenoid contents, including beta
      carotene, as well as vitamin E, tended to increase or remain stable following
      drought exposure, except for the cultivar Sullu, in which the level of these
      lipophilic antioxidants was decreased. Vitamin C contents were not affected by
      drought with the exception of Guincho Negra, in which the level was increased.
      These variations of health-promoting compounds were associated with increased or
      stable levels of the toxic glycoalkaloids, alpha-solanine and alpha-chaconine.
      Storage at 10 degrees C for 4 months tended to decrease the concentrations of all
      dietary antioxidants, except those of vitamin E. This storage also reduced the
      drought-induced variations observed in freshly harvested tubers. These results
      were discussed in terms of their implications for human diet and health as well
      as in plant stress defense mechanisms.

PMID- 19105643
TI  - Bioinspired gradient materials via blending of polymer electrolytes and applying
      electric forces.
AB  - Free-standing and supported films with a lateral gradient in composition were
      prepared using blends of poly(acrylic acid) (PAA)/sodium salt and its copolymers
      with acrylamide (AAm) in an applied electric field. The gradients were stabilized
      by complexation of carboxylate groups with metal species. To find the favorable
      conditions and components for successful blending and interaction with Fe and Ce
      species, we studied blending of the two PAA samples with molecular weights of
      2000 and 15 000 Da with two copolymers of AA and AAm (with 10 and 70 wt % of AA
      units) and interaction of these blends with Fe(III) and Ce(IV) ions. The
      structure of the hybrid (blend) films was studied using differential scanning
      calorimetry (DSC), X-ray photoelectron spectroscopy (XPS), UV-vis spectroscopy, X
      ray diffraction, and optical microscopy. To ensure blend miscibility and
      efficient interaction with metal ions, the copolymer containing 70 wt % AA units
      has been used. The surface enrichment with metal species was observed at all
      experimental conditions studied in this work. For lateral gradient film
      formation, 15 000 Da PAA has been used to avoid uneven distribution of the
      homopolymer in the film, observed for 2000 Da PAA. The gradient films were
      characterized by XPS. The lateral gradient of functionality such as COONa group
      or Fe content has been obtained at different strengths of electric field applied
      during film formation. The use of lower voltage allows one to prevent NaOH
      formation and creates more favorable conditions for development of a gradient
      polymer film. The Ce content gradient was not observed due to formation of large
      Ce oxide particles (> or = 750 nm), masking the gradient of functionality. For
      the first time, free-standing films with a lateral gradient in composition were
      prepared using an applied electric field.

PMID- 19105645
TI  - Neuroprotective effects of glycyrrhizic acid and 18beta-glycyrrhetinic acid in
      PC12 cells via modulation of the PI3K/Akt pathway.
AB  - Glycyrrhizic acid (GA) and 18beta-glycyrrhetinic acid (18betaGA) are the
      bioactive compounds of licorice. The neuroprotective effects of GA and 18betaGA
      against serum/glucose deprivation and 6-hydroxydopamine (6-OHDA)-induced
      cytotoxicity in PC12 cells were investigated. The intracellular reactive oxygen
      species (ROS) content, the activity of the antioxidant enzymes of glutathione
      peroxidase (GPx) and catalase, the mitochondrial membrane potential (MMP), and
      the mitochondrial Bax/Bcl-2 ratio were determined. PI3K/Akt pathway signaling was
      also evaluated to study the possible protective mechanism. The results showed
      that GA treatment decreased the ROS content by elevating the activities of GPx
      and catalase, leading to a decreased MMP. GA and 18betaGA also lowered the
      mitochondrial Bax/Bcl-2 ratio and activated PI3K/Akt signal. The results suggest
      that GA may protect PC12 cells from ischemic injury via modulation of the
      intracellular antioxidant system and mitochondria-induced apoptosis. Moreover, GA
      and 18betaGA may modulate the ratio of the mitochondrial Bcl-2 family and
      influence PI3K/Akt signaling. These results demonstrate the neuroprotective
      ability of GA and 18betaGA and suggest that the cytotoxicity of 6-OHDA may
      influence the mitochondrial Bax/Bcl-2 ratio without altering the expression of
      Bax. This study also suggests a possible compound for treating neural disease and
      general neuronal health.

PMID- 19105646
TI  - Conformational disorder and ultrafast exciton relaxation in PPV-family conjugated
      polymers.
AB  - We report combined experimental and theoretical studies of excitation relaxation
      in poly[2-methoxy,5-(2'-ethyl-hexoxy)-1,4-phenylenevinylene] (MEH-PPV),
      oligophenylenevinylene (OPV) molecules of varying length, and model PPV chains.
      We build on the paradigm that the basic characteristics of conjugated polymers
      are decided by conformational subunits defined by conjugation breaks caused by
      torsional disorder along the chain. The calculations reported here indicate that
      for conjugated polymers like those in the PPV family, these conformational
      subunits electronically couple to neighboring subunits, forming subtly
      delocalized collective states of nanoscale excitons that determine the polymer
      optical properties. We find that relaxation among these exciton states can lead
      to a decay of anisotropy on ultrafast time scales. Unlike in Forster energy
      transfer, the exciton does not necessarily translate over a large distance.
      Nonetheless, the disorder in the polymer chain means that even small changes in
      the exciton size or location has a significant effect on the relaxation pathway
      and therefore the anisotropy decay.

PMID- 19105647
TI  - The hydrothermal and structural chemistry of oxovanadium-arylphosphonate networks
      and frameworks.
AB  - The hydrothermal reactions of NH4VO3 with the aromatic phosphonate ligands 1,4-,
      1,3-, and 1,2-phenylenediphosphonic acids (H4L1, H4L3, H4L4, respectively);
      biphenyl-4,4'-diyldiphosphonic acid (H4L2); and 1,3,5-tris(phenyl)-4,4'
      triphosphonic acid (H6L5) yielded materials of the V(x)O(y)/organophosphonate
      family [VO(H2L1)] (1), [VO(H2L2)] (2), [V2O2(H2O)2(L3)] x 1.5 H2O (3 x 1.5 H2O),
      [V2O2(H2O)2(L4)] x 2 H2O (4 x 2 H2O), and [V3O3(OH)(H3L5)2] x 7.5 H2O (6 x 7.5
      H2O). The reactions were carried out in the presence of HF, and in one case,
      fluoride was incorporated to provide [V2F(OH)(H2O)3(L4)] x 2.25 H2O (5 x 2.25
      H2O). The materials exhibit diverse structural chemistry, including the
      prototypical buttressed layer architecture for 1 and 2, a complex three
      dimensional structure for 3, and unique two-dimensional structures for 4, 5, and
      6. The structures of this oxovanadium-arylphosphonate family are quite distinct
      from those previously described for the V(x)O(y)/alkyldiphosphonate series.

PMID- 19105648
TI  - Crystalline-amorphous core-shell silicon nanowires for high capacity and high
      current battery electrodes.
AB  - Silicon is an attractive alloy-type anode material for lithium ion batteries
      because of its highest known capacity (4200 mAh/g). However silicon's large
      volume change upon lithium insertion and extraction, which causes pulverization
      and capacity fading, has limited its applications. Designing nanoscale
      hierarchical structures is a novel approach to address the issues associated with
      the large volume changes. In this letter, we introduce a core-shell design of
      silicon nanowires for highpower and long-life lithium battery electrodes. Silicon
      crystalline-amorphous core-shell nanowires were grown directly on stainless steel
      current collectors by a simple one-step synthesis. Amorphous Si shells instead of
      crystalline Si cores can be selected to be electrochemically active due to the
      difference of their lithiation potentials. Therefore, crystalline Si cores
      function as a stable mechanical support and an efficient electrical conducting
      pathway while amorphous shells store Li(+) ions. We demonstrate here that these
      core-shell nanowires have high charge storage capacity ( approximately 1000
      mAh/g, 3 times of carbon) with approximately 90% capacity retention over 100
      cycles. They also show excellent electrochemical performance at high rate
      charging and discharging (6.8 A/g, approximately 20 times of carbon at 1 h rate).

PMID- 19105649
TI  - Electrical stimulation of neural stem cells mediated by humanized carbon nanotube
      composite made with extracellular matrix protein.
AB  - One of the key challenges to engineering neural interfaces is to minimize their
      immune response toward implanted electrodes. One potential approach is to
      manufacture materials that bear greater structural resemblance to living tissues
      and by utilizing neural stem cells. The unique electrical and mechanical
      properties of carbon nanotubes make them excellent candidates for neural
      interfaces, but their adoption hinges on finding approaches for "humanizing"
      their composites. Here we demonstrated the fabrication of layer-by-layer
      assembled composites from single-walled carbon nanotubes (SWNTs) and laminin,
      which is an essential part of human extracellular matrix. Laminin-SWNT thin films
      were found to be conducive to neural stem cells (NSC) differentiation and
      suitable for their successful excitation. We observed extensive formation of
      functional neural network as indicated by the presence of synaptic connections.
      Calcium imaging of the NSCs revealed generation of action potentials upon the
      application of a lateral current through the SWNT substrate. These results
      indicate that the protein-SWNT composite can serve as materials foundation of
      neural electrodes with chemical structure better adapted with long-term
      integration with the neural tissue.

PMID- 19105650
TI  - Atomic transportation via carbon nanotubes.
AB  - The transportation of helium atoms in a single-walled carbon nanotube is reported
      via molecular dynamics simulations. The efficiency of the atomic transportation
      is found to be dependent on the type of the applied loading and the loading rate
      as well as the temperature in the process. Simulations show the transportation is
      a result of the van der Waals force between the nanotube and the helium atoms
      through a kink propagation initiated in the nanotube.

PMID- 19105651
TI  - Antilisterial activities of polyphenol-rich extracts of grapes and vinification
      byproducts.
AB  - The quantitation of the main polyphenols and the assessment of the total
      polyphenolic content (TPC) in polyphenol-rich extracts of grape berries and
      vinification byproducts, obtained from Vitis vinifera cultivars of the Greek
      islands, are presented. The results indicated that seed extracts contain high
      concentrations of flavan-3-ols and their derivatives, whereas pomace and stem
      extracts consist of significant amounts of flavonoids, stilbenes, and phenolic
      acids. In particular, stemsa scarcely studied class of grape byproductwere also
      characterized by high trans-resveratrol and epsilon-viniferin content. The
      evaluation of their in vitro antilisterial activities revealed as most potent the
      seed and stem extracts of the red variety Mandilaria. Their minimum inhibitory
      concentrations (MICs) were assessed using a Malthus apparatus by two methods, a
      plate count technique and an automated technique that combines the conductance
      measurements with the common dilution method. The results revealed the usefulness
      of the conductance method as an alternative rapid means for the MIC estimation,
      whereas the respective values (0.26 and 0.34 for seeds and stems) indicated that
      both extracts represent an inexpensive source of potent natural antilisterial
      mixtures, which may be incorporated in food systems to prevent the growth of
      Listeria monocytogenes .

PMID- 19105652
TI  - Observation of graphene bubbles and effective mass transport under graphene
      films.
AB  - Mechanically exfoliated graphene mounted on a SiO2/Si substrate was subjected to
      HF/H(2)O etching or irradiation by energetic protons. In both cases gas was
      released from the SiO2 and accumulated at the graphene/SiO2 interface resulting
      in the formation of "bubbles" in the graphene sheet. Formation of these "bubbles"
      demonstrates the robust nature of single layer graphene membranes, which are
      capable of containing mesoscopic volumes of gas. In addition, effective mass
      transport at the graphene/SiO2 interface has been observed.

PMID- 19105653
TI  - Indolizidine, antiinfective and antiparasitic compounds from Prosopis glandulosa
      var. glandulosa.
AB  - A new potent antiinfective and antiparasitic 2,3-dihydro-1H-indolizinium chloride
      (1) was isolated from Prosopis glandulosa var. glandulosa. Three additional new
      (2-4) and one known (5) indolizidines were also isolated, and the dihydrochloride
      salts of 1-3 (compounds 6, 7, and 8) were prepared. Structures were determined by
      1D and 2D NMR and mass spectra. Compound 1 showed potent in vitro antifungal
      activity against Cryptococcus neoformans and Aspergillus fumigatus (IC(50) values
      = 0.4 and 3.0 microg/mL, respectively) and antibacterial activity against
      methicillin-resistant Staphylococcus aureus and Mycobacterium intracellulare
      (IC(50) values of 0.35 and 0.9 microg/mL, respectively). The remarkable in vitro
      fungicidal activity of 1-4 against C. neoformans (MFCs = 0.63-1.25 microg/mL) and
      2, 3, and 5 against A. fumigatus (MFCs = 0.63-2.5 microg/mL) were similar to
      amphotericin B, but >2-4-fold more potent than 6-8. Prosopilosidine (1) showed
      potent in vivo activity at 0.0625 mg/kg/day/ip for 5 days in a murine model of
      cryptococcosis by eliminating approximately 76% of C. neoformans infection from
      brain tissue compared to approximately 83% with amphotericin B at 1.5 mg/kg/day.
      Compounds 1 and 4 exhibited potent activity and high selectivity index (SI)
      values against chloroquine-sensitive (D6) and chloroquine-resistant (W2) strains
      of Plasmodium falciparum, with IC(50) values of 39 and 95 ng/mL and 42 and 120
      ng/mL, respectively (chloroquine, IC(50) = 17 and 140 ng/mL). Prosopilosine (1)
      also showed in vivo antimalarial activity, with an ED(50) value of approximately
      2 mg/kg/day/ip against Plasmodium berghei-infected mice after 3 days of
      treatment.

PMID- 19105654
TI  - Well-defined, multifunctional nanostructures of a paramagnetic lipid and a
      lipopeptide for macrophage imaging.
AB  - In the field of nanomedicine there is a great demand for technologies that allow
      the creation of self-assembled structures of which the size and morphology can be
      accurately controlled. In the current study, we report a nanoparticle platform
      that is composed of a paramagnetic lipid and a fluorescently labeled lipopeptide.
      By judiciously controlling the ratio of the aforementioned amphiphilic molecules,
      a variety of well-defined nanosized supramolecular structures with different
      sizes and morphologies could be created. The hydrodynamic radii of the different
      structures were determined by dynamic light scattering. Cryo-TEM revealed the
      aggregate morphology to vary from small micellar structures to plate-like and
      even full grown ribbons of which the aspect ratios varied from a diameter of 5-8
      nm to structures with a width of up to 25 nm and infinite length. Interestingly,
      nuclear magnetic resonance dispersion profiling revealed excellent properties for
      MRI and also showed that the relaxivity of the structures was tunable and
      morphology dependent. Finally, macrophage cells were treated with two selected
      nanoparticles and were shown to be avidly taken up. In conclusion we demonstrate
      a methodology to create structures that (1) are paramagnetic to enable their
      detection with MRI, (2) exhibit fluorescent properties, (3) can be tuned to
      defined sizes and shapes, and (4) are efficiently taken up by macrophage cells in
      vitro.

PMID- 19105656
TI  - Total synthesis without protecting groups: pyrrolidines and cyclic carbamates.
AB  - A protecting group free synthesis of 2,3-cis substituted hydroxypyrrolidines is
      reported. Two novel reaction methodologies allow for the stereoselective
      formation of cyclic carbamates from olefinic amines, and the formation of primary
      amines via a Vasella/reductive amination reaction, both performed in aqueous
      media.

PMID- 19105657
TI  - Enhancing immunity through autophagy.
AB  - Next to the proteasome, autophagy is the main catabolic pathway for the
      degradation of cytoplasmic constituents. The immune system uses it both as an
      effector mechanism to clear intracellular pathogens and as a mechanism to monitor
      its products for evidence of pathogen invasion and cellular transformation.
      Because autophagy delivers intracellular material for lysosomal degradation, its
      products are primarily loaded onto MHC class II molecules and are able to
      stimulate CD4+ T cells. This process might shape the self-tolerance of the CD4+ T
      cell repertoire and stimulate CD4+ T cell responses against pathogens and tumors.
      Beyond antigen processing, autophagy's role in cell survival is to assist the
      clonal expansion of B and T cells for efficient adaptive immune responses. These
      immune-enhancing functions make autophagy an attractive target for therapeutic
      manipulation in human disease.

PMID- 19105658
TI  - Docking studies on a new human immunodeficiency virus integrase-Mg-DNA complex:
      phenyl ring exploration and synthesis of 1H-benzylindole derivatives through
      fluorine substitutions.
AB  - A new model of HIV-1 integrase-Mg-DNA complex that is useful for docking
      experiments has been built. It was used to study the binding mode of integrase
      strand transfer inhibitor 1 (CHI-1043) and other fluorine analogues. Molecular
      modeling results prompted us to synthesize the designed derivatives which showed
      potent enzymatic inhibition at nanomolar concentration, high antiviral activity,
      and low toxicity. Microwave assisted organic synthesis (MAOS) was employed in
      several steps of the synthetic pathway, thus reducing reaction times and
      improving yields.

PMID- 19105659
TI  - Enantioselective sequential conjugate addition-allylation reactions: a concise
      total synthesis of (+)-podophyllotoxin.
AB  - A highly flexible and concise total synthesis of (+)-podophyllotoxin featured
      with an enantioselective sequential conjugate addition-allylation reaction was
      reported. Starting from commercially available 3,4,5-trimethoxycinnamic acid,
      this new route leads to (+)-podophyllotoxin 1 in only eight steps with 29%
      overall yield.

PMID- 19105661
TI  - Alternative activation of macrophages: an immunologic functional perspective.
AB  - Macrophages are innate immune cells with well-established roles in the primary
      response to pathogens, but also in tissue homeostasis, coordination of the
      adaptive immune response, inflammation, resolution, and repair. These cells
      recognize danger signals through receptors capable of inducing specialized
      activation programs. The classically known macrophage activation is induced by
      IFN-gamma, which triggers a harsh proinflammatory response that is required to
      kill intracellular pathogens. Macrophages also undergo alternative activation by
      IL-4 and IL-13, which trigger a different phenotype that is important for the
      immune response to parasites. Here we review the cellular sources of these
      cytokines, receptor signaling pathways, and induced markers and gene signatures.
      We draw attention to discrepancies found between mouse and human models of
      alternative activation. The evidence for in vivo alternative activation of
      macrophages is also analyzed, with nematode infection as prototypic disease.
      Finally, we revisit the concept of macrophage activation in the context of the
      immune response.

PMID- 19105662
TI  - IPEG guidelines for appendectomy.

PMID- 19105660
TI  - Protein side-chain dynamics and residual conformational entropy.
AB  - Changes in residual conformational entropy of proteins can be significant
      components of the thermodynamics of folding and binding. Nuclear magnetic
      resonance (NMR) spin relaxation is the only experimental technique capable of
      probing local protein entropy, by inference from local internal conformational
      dynamics. To assess the validity of this approach, the picosecond-to-nanosecond
      dynamics of the arginine side-chain N(epsilon)-H(epsilon) bond vectors of
      Escherichia coli ribonuclease H (RNase H) were determined by NMR spin relaxation
      and compared to the mechanistic detail provided by molecular dynamics (MD)
      simulations. The results indicate that arginine N(epsilon) spin relaxation
      primarily reflects persistence of guanidinium salt bridges and correlates well
      with simulated side-chain conformational entropy. In particular cases, the
      simulations show that the aliphatic part of the arginine side chain can retain
      substantial disorder while the guanidinium group maintains its salt bridges;
      thus, the N(epsilon)-H(epsilon) bond-vector orientation is conserved and side
      chain flexibility is concealed from N(epsilon) spin relaxation. The MD
      simulations and an analysis of a rotamer library suggest that dynamic decoupling
      of the terminal moiety from the remainder of the side chain occurs for all five
      amino acids with more than two side-chain dihedral angles (R, K, E, Q, and M).
      Dynamic decoupling thus may represent a general biophysical strategy for
      minimizing the entropic penalties of folding and binding.

PMID- 19105663
TI  - IPEG guidelines for the surgical treatment of pediatric gastroesophageal reflux
      disease (GERD).

PMID- 19105664
TI  - IPEG guidelines for surgical treatment of extremely obese adolescents.

PMID- 19105665
TI  - Laparoscopic Heller myotomy for achalasia: changing trend toward "true" day-case
      procedure.
AB  - BACKGROUND: Laparoscopic Heller myotomy is the most effective therapy for
      achalasia. All case series have reported a minimum length of stay of more than 1
      day. "True" day-case laparoscopic Heller myotomy has not been reported, so far.
      The aim of this study was to review our results with laparoscopic Heller myotomy
      with respect to the length of stay following the procedure. METHODS: All patients
      undergoing laparoscopic Heller myotomy between August 2000 and July 2007 under
      the care of one surgeon were included in the study. This was performed by
      incising 6 cm of distal esophageal musculature, extending to 2 cm below the
      gastroesophageal junction. The myotomy was covered by an anterior fundoplication.
      All patients were reviewed in the clinic at a median of 6 weeks after surgery
      and, thereafter, if necessary. RESULTS: Over the 7-year period, 24 consecutive
      patients with achalasia were treated in this manner. There were 13 women and 11
      men, with an age range of 12-73 years. Intraoperative complications included
      mucosal perforation in 2 patients (sutured immediately) with no postoperative
      complications or conversion to open surgery. There were no deaths. The average
      length of stay was 1.9 days (range, 0-4). The last 2 patients were discharged on
      the same day, and the 5 previous to this were discharged within 23 hours of
      surgery. There were no adverse outcomes related to early discharge, and there
      were no readmissions. All patients reported good to excellent results with a
      relief of dysphagia on follow-up. Three patients (12%) developed recurrent
      dysphagia after an initial improvement, requiring dilatation only several months
      later. CONCLUSIONS: Based on our own experience, we believe that laparoscopic
      Heller myotomy with anterior partial fundoplication is safe and achieves a good
      outcome in the treatment of achalasia. It is well tolerated and can be considered
      a true day-case procedure.

PMID- 19105666
TI  - Outcome of surgical fundoplication for extraesophageal (atypical) manifestations
      of gastroesophageal reflux disease in adults: a systematic review.
AB  - BACKGROUND: A significant proportion of patients with gastroesophageal reflux
      disease (GERD) present with atypical symptoms (extraesophageal reflux; EER). The
      effectiveness of surgical fundoplication in treating classical reflux symptoms is
      well documented, but the role of surgery in alleviating EER symptoms is less
      clear. The aim of this study was to review the published literature to determine
      whether surgical fundoplication is effective in controlling EER. MATERIALS AND
      METHODS: A Medline, PubMed, and Cochrane database search was done to find
      articles on surgery for extraesophageal reflux (1991-2006). Articles on pediatric
      patients were excluded. The parameters looked at were patient selection,
      resolution of symptoms, change in the quality of life, and any adverse outcomes.
      RESULTS: In 25 studies, a variable proportion (15-95%) of patients with various
      symptoms of EOR improved after surgical fundoplication. The percentage of
      patients with EER responding to surgery was less than that reported for classical
      GERD. CONCLUSIONS: The majority of patients in most studies seem to improve
      symptomatically after surgery. However, a small percentage remains unchanged or
      worsens. The reported studies are so disparate in their methodology that firm
      conclusions on the role of surgery are difficult. Further studies are needed.
      These should be large, multicenter, prospective trials comparing medical and
      surgical treatment with standardized diagnostic criteria for EER. Pre- and post
      treatment assessment, the type of surgery performed, and follow-up should be
      standardized.

PMID- 19105667
TI  - Total extraperitoneal hernioplasty: does the long-term clinical course depend on
      the type of mesh?
AB  - INTRODUCTION: Implantation of alloplastic material has become a standard surgical
      procedure in inguinal hernia repair. The properties of different meshes are
      discussed as determinants of postoperative outcome. The aim of this study was to
      comparatively evaluate long-term results after total extraperitoneal hernioplasty
      (TEP) with a heavyweight polypropylene mesh (PP) and a lightweight polypropylene
      polyglactin composite mesh (PP-PG) in a large patient population. MATERIALS AND
      METHODS: The study included patients who underwent TEP for elective repair of uni
      or bilateral inguinal hernias between June 1997 and October 2004. We used a
      heavyweight PP mesh from June 1997 to February 2001 and a lightweight PP-PG mesh
      from March 2001 to October 2004. Patient data were evaluated by a prospective
      online registry, and long-term results were assessed by standardized ad hoc
      questionnaires after a minimum follow-up of 12 (12-103) months. RESULTS: Five
      hundred twenty-two patients aged 18-87 years underwent surgical repair of 655
      inguinal hernias, and 370 (70.8%) were evaluated. TEP was performed with PP mesh
      in 192 cases and with PP-PG mesh in 169 cases. Nine patients died during follow
      up; 14.6% (PP) versus 20.1% (PP-PG) patients complained of mild pain, and 8.9%
      (PP) versus 5.3% (PP-PG) patients reported moderate to severe pain (P > 0.05).
      Mild dysesthesias occurred in 13.5% of the PP group and 11.8% of the PP-PG group
      (P = 0.63). Moderate to severe dysesthesias were reported by 6.8% with a
      heavyweight mesh and by 3.0% with a lightweight mesh (P = 0.10). There were no
      significant differences with regard to the patients' postoperative return to
      normal daily activities. The recurrence rate was 5.2% with a PP mesh and 1.8%
      with a PP-PG mesh (P = 0.08). CONCLUSIONS: The long-term results after TEP showed
      no difference between PP and PP-PG meshes with regard to chronic pain, chronic
      dysesthesias, postoperative daily activities, and recurrence rates.

PMID- 19105668
TI  - Selection of cap size in endoscopic submucosal resection with cap aspiration for
      rectal carcinoid tumors.
AB  - BACKGROUND: Small rectal carcinoid tumors (<or=1 cm in diameter) can be treated
      by endoscopic resection, but complete resection may be difficult if tumors are
      located in the deep submucosal layer. This study was performed to identify the
      clinicopathologic factors affecting the complete resection of small rectal
      carcinoid tumors, using the endoscopic submucosal resection with cap aspiration
      technique (ESMR-C). MATERIALS AND METHODS: Forty-one consecutive patients with 42
      rectal carcinoid tumors who underwent ESMR-C from October 2003 to November 2006
      were assessed. Complete resection was defined as a clean margin that was free of
      tumor invasion at the lateral and inferior edges. RESULTS: The rate of complete
      tumor removal by ESMR-C was 85.7% and no complications occurred. The tumor size,
      location, and method of resection did not significantly affect the completeness
      of resection. Univariate analysis showed that the rate of complete resection was
      significantly higher when using 19.2-mm, compared with 13.9-mm, caps (96.0 vs.
      70.6%; P = 0.032). Multivariate analysis showed that the cap size was an
      independent factor predicting the completeness of resection. CONCLUSION: The use
      of large-sized caps increases the completeness of the resection of rectal
      carcinoid tumors when using ESMR-C.

PMID- 19105669
TI  - Comparison of torsional and linear mode ultrasonic coagulating shears for sealing
      veins.
AB  - BACKGROUND: Torsional mode ultrasonic coagulating shears are an alternative
      device to linear mode shears for hemostatic cutting. The aim of this study was to
      compare the vessel-sealing quality of torsional and linear mode ultrasonic
      coagulating shears on human veins. MATERIALS AND METHODS: Veins were harvested
      from 15 patients during varicose vein surgery. Each vessel was sealed and cut by
      both devices at different sites. The seals were either tested for burst pressure
      or examined microscopically to compare mural thickness, seal length, and extent
      of coagulation and lateral thermal effect. RESULTS: For veins 2.0-3.0 mm in
      diameter, the median burst pressure was higher on seals made with torsional mode
      shears (245, IQR 161-360 mm Hg vs. 133, IQR 101-165 mm Hg; P = 0.001). Similarly,
      for veins 3.5-4.5 mm in diameter, the median burst pressure was higher with
      torsional mode shears (149, IQR 118-212 mm Hg vs. 94, IQR 82-126 mm Hg; P =
      0.001). There was no significant difference in the median burst pressure for
      veins 5.0-6.0 mm in diameter (82, IQR 61-132 mm Hg vs. 76, IQR 40-114 mm Hg; P =
      0.268). Seals made with torsional mode shears showed significantly greater seal
      length (517 +/- 300 microm vs. 316 +/- 147 microm; P = 0.016), more tissue
      coagulation (467 +/- 197 microm vs. 335 +/- 128 microm; P = 0.015), and greater
      lateral thermal effect (1479 +/- 340 microm vs. 1116 +/- 253 mum; P < 0.001).
      CONCLUSION: Torsional mode ultrasonic shears produced more secure seals on veins
      up to 4.5 mm in diameter. This can be explained by the greater seal length
      produced by torsional mode shears.

PMID- 19105670
TI  - Laparoscopic bladder diverticulectomy.
AB  - Acquired bladder diverticulae are herniations of the bladder mucosa through
      detrusor muscle. Due to the ineffective emptying of the bladder diverticulum,
      urine accumulation may lead to urinary tract infection, stone disease, and lower
      urinary tract malignancy in the diverticulum. We report a case of laparoscopic
      bladder diverticulectomy for transitional cell carcinoma in an acquired bladder
      diverticulum. To our knowledge, this is the third case of laparoscopic
      diverticulectomy for a tumor. We report our experience with this case and the
      technical challenges encountered during the operation, together with literature
      review.

PMID- 19105671
TI  - Habib laparoscopic bipolar radiofrequency device: a novel way of creating an
      avascular resection margin in laparoscopic partial nephrectomy.
AB  - INTRODUCTION: Hemostasis during the laparoscopic partial nephrectomy (LPN) is a
      challenge. Usually, the renal hilum is clamped to minimize blood loss. However,
      prolonged ischemia leads to irreversible damage. Therefore, new technology is
      needed to minimize blood loss while performing LPN without hilar clamping. The
      Habib 4x Laparoscopic device (Angio Dynamics, Queensbury, NY) is a four-pronged
      bipolar radiofrequency probe that is proven to reduce blood loss in laparoscopic
      liver resections without hilar clamping. The aim of this pilot study was to
      evaluate this new technology in LPN. METHODS: Three patients, with exophytic
      renal lesions (1.1-4 cm), underwent LPN without hilar clamping, using the Habib
      Laparoscopic device to create an avascular resection margin. RESULTS: Mean
      operative time was 150.3 minutes, mean estimated blood loss was 100 cc, and none
      of the patients required transfusions. There was no significant difference
      between the mean pre- and postoperative serum creatinine levels (P > 0.05). All 3
      resected masses were renal-cell carcinomas. Intraoperative frozen sections
      demonstrated negative margins in all cases. However, in the second case, with a
      renal lesion of 4 cm, the permanent section analysis on margins was read as
      focally positive. There were no complications. On follow-up imaging of up to 12
      months, there were no recurrences. CONCLUSIONS: The Habib 4x Laparoscopic device
      permits the resection of exophytic renal lesions without the need for hilar
      clamping. However, a cautery artifact can cause difficulty in interpreting the
      frozen-section analysis of resection margins. Therefore, its use should be
      restricted to lesions of less than 2 cm.

PMID- 19105672
TI  - Radiofrequency ablation of liver tumors using a novel bipolar device.
AB  - PURPOSE: Radiofrequency ablation (RFA) is now an established tool for treating
      unresectable liver tumors. Monopolar RFA is currently the accepted standard.
      However, the variability of the ablation shape and size impedes their further
      advancement. For this study, we were interested in the evaluation of a new
      bipolar device for technical feasibility. PATIENTS AND METHODS: We have treated 6
      patients [5 with hepatocellular carcinoma (HCC) one with metastatic disease] with
      a total of 7 tumors (6 HCCs, a solitary metastasis), using a new bipolar RFA
      device consisting of two separate needles, each with deployable electrodes. The
      treatment approaches included two percutaneous, three laparoscopic, and one open
      surgical. Average tumor size was 2.5 cm. Follow-up examinations were performed at
      intervals of 3 months and included computed tomography, (18)fluorodeoxyglucose
      positron emission tomography, magnetic resonance imaging and B-mode ultrasound.
      RESULTS: All tumors could be ablated successfully. Electrode placement was
      accurate and visualization in transabdominal, laparoscopic, or intraoperative
      ultrasound was excellent. Because of the requirement of positioning two needles
      simultaneously, particularly in the laparoscopic RFA, the procedures were more
      time-consuming (average, 104 minutes) than placing a single needle. Local tumor
      control after a follow-up of 6 months was 100%. No major complication occurred.
      CONCLUSIONS: Successful ablation of liver tumors, using the new bipolar device,
      is feasible and without complications. The procedure is technically demanding;
      however, local tumor control seems to be superior, as compared to other RFA
      devices. The long-term success of the procedure has yet to be evaluated.

PMID- 19105673
TI  - Outcome of primary endorectal pull-through for the treatment of classic
      Hirschsprung disease.
AB  - INTRODUCTION: Endorectal pull-through (ERPT) is a widely accepted procedure for
      the treatment of Hirschsprung's disease (HSCR). This study was aimed at
      presenting the long-term results of patients with classic HSCR who were operated
      on with a laparoscopic-assisted Georgeson procedure and to compare them to
      patients treated with a Soave-Boley procedure. PATIENTS AND METHODS: Patients
      treated for Hirschsprung disease in the period 1997-2006 with a minimum follow-up
      of 6 months were prospectively included in this study. Demographic details,
      associated anomalies, surgical technique, length of aganglionosis, and
      postoperative complications were collected. A questionnaire was submitted to all
      families to assess general health, bowel adaptation, fecal and urinary
      continence, cosmetic results, and patients' and parents' perspective of overall
      outcome. RESULTS: Overall, 162 patients underwent a pull-through procedure: 25
      patients treated with Georgeson and 21 with Soave-Boley ERPT were eligible for
      this study. Conversion was required in 3 of 28 patients approached
      laparoscopically. Hospitalization was shorter for patients treated
      laparoscopically (P < 0.05), whereas length of surgery was comparable.
      Complication rate was similar for both groups, as well as growth that remained
      within normal ranges for age. Long-term outcome, in terms of bowel movements, was
      similar. None of the patients experienced fecal and/or urinary incontinence.
      Cosmetic results proved to be excellent to good in all patients undergoing the
      Georgeson and in 67% of patients undergoing the Soave-Boley procedure (P < 0.05).
      Patients' perspective of overall outcome was excellent in more than 90% of
      patients from both groups. CONCLUSIONS: Overall results proved to be similar.
      Likewise, long-term bowel function did not show significant differences.
      Nonetheless, if we consider hospitalization and cosmetic results, it becomes
      clear that the minimally invasive approach should be preferred, when possible, to
      improve patients' comfort, perspective of overall health status, and psychologic
      acceptance.

PMID- 19105674
TI  - Thoracoscopic repair of neonatal diaphragmatic hernia.
AB  - INTRODUCTION: The use of minimally invasive surgery (MIS) in the neonatal
      population is increasing. Thoracoscopic intervention for congenital diaphragmatic
      hernia (CDH) is no exception. In this report, we describe our initial experience
      with thoracoscopic repair of left-sided diaphragmatic defects in neonates.
      MATERIALS AND METHODS: We performed retrospective chart reviews on all neonates
      who underwent thoracoscopic repair of CDH between November 2004 and January 2008.
      Neonates that underwent thoracoscopic repair were physiologically stable with
      resolved pulmonary hypertension and minimal to moderate ventilatory support. They
      had no associated cardiac anomalies. RESULTS: We identified 15 neonates with CDH
      who underwent thoracoscopic repair during the study period. Ten neonates
      underwent primary repair of the diaphragmatic defect. Five neonates with large
      defects required closure with a synthetic patch, which was placed
      thoracoscopically. The average operating room time was 134 minutes. There were no
      instances of intraoperative respiratory or cardiac instability. Three patients
      had a recurrence. One recurrence was seen after thoracoscopic patch repair. Two
      recurrences occurred following primary repair of left diaphragmatic hernias.
      There were no deaths. Follow-up has been 4-40 months. CONCLUSIONS: Neonatal MIS
      for CDH should be limited to stable patients. The ideal candidate is the newborn
      without associated anomalies, not requiring extracorporeal membrane oxygenation,
      on minimal ventilatory support, and without evidence of pulmonary hypertension.
      It is technically possible to perform thoracoscopic repair with a patch.

PMID- 19105675
TI  - Impact of minimally invasive surgery on the pediatric surgical profession.
AB  - We conducted a survey among pediatric surgeons to examine the impact of the
      advent of minimally invasive surgery (MIS) on the pediatric surgical profession
      with respect to job satisfaction and training challenges. An invitation to
      participate in a web-based questionnaire was sent out to 306 pediatric surgeons.
      Apart from demographic details and training recommendations, parameters relevant
      to job satisfaction, including patient interaction, peer pressure, ethical
      considerations, academic progress, ability to train residents, and financial
      remuneration, were studied. The response rate was 38.2%. Working in a unit
      performing MIS was identified by 71% of respondents as the most effective and
      feasible modality of training in MIS. Inability to get away from a busy practice
      was the most common reason cited for inability to acquire MIS training. The
      overall responses to the job satisfaction parameters showed a positive trend in
      the current MIS era for patient interaction, ethical considerations, academic
      progress, and training residents, with a negative trend for peer pressure and
      financial remuneration. The enthusiastic minimally invasive surgeons (EMIS) were
      defined as those having more than 5 years of MIS experience and also performing
      more than 10% of their work using MIS. Of the 113 responses analyzed, 67 belonged
      to the EMIS category. Those belonging to the EMIS group were less likely to feel
      inadequate in training their residents, in meeting the felt needs of the
      patients, or to complain about peer pressure. They were more likely to consider
      MIS to be as relevant and beneficial in children as in adults. Embracing MIS, as
      represented by the EMIS group, correlated with an overall greater job
      satisfaction.

PMID- 19105676
TI  - Laparoscopic ligation of internal ring-three ports versus single-port technique:
      are working ports necessary?
AB  - BACKGROUND: From three ports, technical refinements in laparoscopy have
      facilitated the ligation of the internal ring (IR) with a single port.
      OBJECTIVES: The aims of this study were to determine whether, when, and where
      working ports are needed by assessing the differences in outcome between the
      three-port technique (TPT) and the single-port technique-subcutaneous
      endoscopically assisted ligation (SEAL). METHODS: Short-term outcomes of 163
      children operated on by either technique (51 with TPT, and 112 with SEAL) were
      audited. Technical difficulties, operation time, intra- and postoperative
      complications, and postoperative stay were studied. RESULTS: IR could be ligated
      faster by SEAL than TPT (unilateral: 15 vs. 25 minutes; P = 0.0005; bilateral: 25
      vs. 40 minutes; P = 0.001). SEAL proved cosmetically more appealing (one 5-mm vs.
      three 5-mm scars). Complication rates, recovery, and hospital stay were similar.
      Recurrences were marginally higher following SEAL (4.8 vs. 2.98%; P = 0.49).
      Intracorporeal suturing and knotting were the limiting steps in TPT, while wide
      rings (>10 mm) and thick abdominal wall were the limitations of SEAL.
      CONCLUSIONS: Both TPT and SEAL are safe and efficacious day-care procedures. In
      the ligation of average-sized IR of thin patients, working ports may not be
      necessary, as SEAL proves cosmetically and temporally efficacious over TPT.
      However, patients with wide rings and thick anterior abdominal walls may need the
      placement of working ports for successful laparoscopic repair.

PMID- 19105677
TI  - Ovarian reconstitution following laparoscopic decapsulation of congenital cyst.
AB  - Laparoscopic management of congenital ovarian cysts is widely practiced but there
      is a dearth of information on the performance of the gonad where organ-preserving
      surgery is undertaken. Presented is a radiological diary documenting the progress
      of a complex congenital ovarian cyst from the antenatal period to a year post
      laparoscopic decapsulation.

PMID- 19105678
TI  - Laparoscopic partial splenectomy for splenic epidermoid cyst.
AB  - The treatment strategy of the splenic cyst is controversial. Better understanding
      of the splenic segmental anatomy, need of splenic conservation, and advances in
      laparoscopic skills has made laparoscopic partial splenectomy a preferred
      treatment for splenic cysts. In this paper, we report a case of splenic
      epidermoid cyst managed successfully by laparoscopic partial splenectomy. Also,
      results of various treatment strategies were reviewed.

PMID- 19105679
TI  - Toward optimal health: a renewed look at stroke in women. Interview by Jodi R.
      Godfrey.

PMID- 19105680
TI  - Ru-TsDPEN with formic acid/Hunig's base for asymmetric transfer hydrogenation, a
      practical synthesis of optically enriched N-propyl pantolactam.
AB  - The Noyori-Ikariya catalysts, Ru-TsDPEN 1 or 2, in combination with HCOOH/Hunig's
      base (5:2) have been successfully utilized for catalytic asymmetric transfer
      hydrogenation of alpha-ketopantolactam, and optically enriched N-substituted
      pantolactam was prepared (S/C = 500, up to 95% ee and 99% conversion in
      HCOOH/Hunig's base condition). More than 2 kg of this key intermediate 9 has been
      synthesized efficiently with excellent chemical yield and chiral purity.

PMID- 19105682
TI  - PQS: a new platform for micellar catalysis. RCM reactions in water, with catalyst
      recycling.
AB  - The first "designer" surfactant containing a covalently bound ruthenium catalyst
      is reported. This species dissolves freely in water, forming nanomicelles in
      which ring-closing metathesis reactions on water-insoluble dienic substrates can
      occur in pure water at room temperature. It can also be recycled continuously
      without reaction workup.

PMID- 19105681
TI  - Do carotid artery diameters manifest early evidence of atherosclerosis in women
      with rheumatoid arthritis?
AB  - OBJECTIVE: Given the high incidence of cardiovascular disease (CVD) in patients
      with rheumatoid arthritis (RA), we examined the associations between RA diagnosis
      and characteristics and evidence of carotid atherosclerosis. We take a unique
      approach by evaluating lumen and interadventitial diameters in addition to intima
      media thickness and plaque. METHODS: Ninety-three women with RA were matched with
      93 healthy women by age, race, and menopause status. In cross-sectional analyses,
      we compared common carotid artery measures between groups and examined their
      relationships with measures of RA severity and activity. RESULTS: Mean age was
      53.3 years, and median RA duration was 14 years. Lumen diameter in patients was
      significantly greater than in healthy women (5.50 vs. 5.19 mm, p < 0.001), as was
      interadventitial diameter (6.92 vs. 6.61 mm, p < 0.001). Having RA also was
      independently associated with greater lumen (beta = 0.256, p < 0.01) and
      interadventitial (beta = 0.261, p < 0.01) diameters, after controlling for
      cardiovascular risk factors and intima-media thickness. Carotid intima-media
      thickness (0.70 vs. 0.71 mm) was similar, and the prevalence of carotid plaque in
      patients (21%) was higher but not statistically different from healthy women
      (15%). In patients with RA, we found positive associations between methotrexate
      dose and interadventitial diameter, between hypothyroidism and intima-media
      thickness, and between hypothyroidism and soluble endothelial adhesion molecule
      and plaque, independent of cardiovascular risk factors. CONCLUSIONS: Women with
      RA have increased carotid artery diameters compared with healthy women. This may
      reflect premature vascular aging and may be an early indicator of increased
      cardiovascular risk.

PMID- 19105684
TI  - Nucleophilicity parameters for phosphoryl-stabilized carbanions and phosphorus
      ylides: implications for Wittig and related olefination reactions.
AB  - The kinetics of the reactions of four phosphoryl-stabilized carbanions 1a-d and
      four phosphorus ylides 1e-h with benzhydrylium ions 2a-h and structurally related
      quinone methides 2i-m have been determined by UV-vis spectroscopy. The second
      order rate constants (k) correlated linearly with the electrophilicity parameters
      E of 2a-m, as required by the correlation log k = s(N + E) (J. Am. Chem. Soc.
      2001, 123, 9500-9521), allowing us to calculate the nucleophile-specific
      parameters N and s for phosphoryl-substituted carbanions and phosphorus ylides.
      In this way, a direct comparison of the nucleophilic reactivities of Horner
      Wadsworth-Emmons carbanions and Wittig ylides became possible. Ph(2)PO- and
      (EtO)(2)PO-substituted carbanions are found to show similar reactivities toward
      Michael acceptors, which are 10(4)-10(5) times higher than those of analogously
      substituted phosphorus ylides. The relative reactivities of these nucleophiles
      toward benzaldehydes differ significantly from those toward carbocations and
      Michael acceptors, in accordance with a concerted [2 + 2] cycloaddition being the
      initial step of these olefinations reactions. Effects of the counterion (K(+),
      Na(+), or Li(+)) on the nucleophilicities of the phosphoryl-stabilized carbanions
      in DMSO have been studied. Whereas the effects of K(+) and Na(+) are almost
      negligible for all types of carbanions investigated, Li(+) coordination reduces
      the reactivities of phosphonate-substituted acetic ester anions (1a) by a factor
      of 10(2) while the reactivities of phosphonate-substituted acetonitrile anions
      (1b) remain almost unaffected.

PMID- 19105683
TI  - Premenstrual syndrome prevalence and fluctuation over time: results from a French
      population-based survey.
AB  - OBJECTIVES: To explore the experience of reproductive-age women in the French
      population with premenstrual syndrome (PMS) by estimating perceived symptom
      prevalence, identifying risk factors, and quantifying the burden of symptoms.
      This study also assesses the stability of the PMS diagnosis over a 1-year period
      of follow-up. METHODS: The prevalence of reported PMS was estimated from a
      population-based cohort of 2863 French women interviewed in 2003 and 2004.
      Multivariate logistic regressions were used to identify risk factors associated
      with PMS. PMS fluctuation was studied by comparing women's responses in 2003 and
      2004. RESULTS: Results show that 4.1% of women qualified for severe PMS (six
      symptoms) and 8.1% qualified for moderate PMS (one to five symptoms), resulting
      in 12.2% of women who reported PMS symptoms that impacted their daily lives. Risk
      factors for PMS fell into three categories: hormonal, psychosocial, and
      physiological, with life stressors and exogenous hormonal exposure exerting the
      most substantial impact. Results also indicate a high level of intraindividual
      variation in PMS status over time; among women who qualified for PMS during 1 or
      both years of the study, 72% demonstrated fluctuation in their PMS status.
      CONCLUSIONS: More women report suffering from distressing premenstrual symptoms
      than are captured by strict premenstrual dysphoric disorder (PMDD) diagnostic
      criteria. The impact of PMS symptoms on women appears to fluctuate over time,
      however, producing greater variability in the syndrome than previously
      recognized. Clinicians should be mindful of high intraindividual variability in
      the syndrome when advising patients about long-term management.

PMID- 19105685
TI  - Formation of ferrimagnetic films with functionalized magnetite nanoparticles
      using the Langmuir-Blodgett technique.
AB  - The formation of ferrimagnetic films of 39 nm magnetite nanoparticles
      functionalized by stilbene derivatives has been studied using the Langmuir
      Blodgett technique. The stilbene moieties are grafted to the particles either via
      a phosphonate or a carboxylate group; in both cases the nanoparticles display
      similar isotherms although the microscopic initial and final states of the films
      are different. Two different mechanisms of film formation are proposed, based on
      the inorganic-organic bond stability.

PMID- 19105687
TI  - Layer-by-layer assembly of all carbon nanotube ultrathin films for
      electrochemical applications.
AB  - All multiwall carbon nanotube (MWNT) thin films are created by layer-by-layer
      (LBL) assembly of surface functionalized MWNTs. Negatively and positively charged
      MWNTs were prepared by surface functionalization, allowing the incorporation of
      MWNTs into highly tunable thin films via the LBL technique. The pH dependent
      surface charge on the MWNTs gives this system the unique characteristics of LBL
      assembly of weak polyelectrolytes, controlling thickness and morphology with
      assembly pH conditions. We demonstrate that these MWNT thin films have randomly
      oriented interpenetrating network structure with well developed nanopores using
      AFM and SEM, which is an ideal structure of functional materials for various
      applications. In particular, electrochemical measurements of these all-MWNT thin
      film electrodes show high electronic conductivity in comparison with polymer
      composites with single wall nanotubes, and high capacitive behavior with precise
      control of capacity.

PMID- 19105686
TI  - Mammography screening after risk-tailored messages: the women improving screening
      through education and risk assessment (WISER) randomized, controlled trial.
AB  - AIMS: A randomized trial investigated the impact of risk-tailored messages on
      mammography in diverse women in the Virginia Commonwealth University Health
      System's gynecology clinics. METHODS: From 2003 to 2005, 899 patients > or =40
      years of age were randomized to receive risk-tailored information or general
      information about breast health. Multiple logistic regression analyses summarize
      their breast health practices at 18 months. RESULTS: At baseline, 576 (64%) women
      reported having a mammogram in the past year. At 18-month follow-up, mammography
      rates were 72.6% in the intervention group and 74.2% in the control group (N.S.).
      Women (n = 123) who reported worrying about breast cancer "often" or "all the
      time" had significantly higher mammography rates with the intervention (85.0%)
      vs. the controls (63.5%). No significant differences existed in clinical breast
      examination, self-examination, or mammography intentions between the two study
      arms. However, intervention women with lower education reported significantly
      fewer clinical breast examinations at follow-up. CONCLUSIONS: The brief
      intervention with a risk-tailored message did not have a significant effect
      overall on screening at 18 months. However, among those who worried, mammography
      rates in the intervention group were higher. Individual characteristics, such as
      worry about breast cancer and education status, may impact interventions to
      improve breast cancer prevention practices.

PMID- 19105688
TI  - Exploring health by reproductive status: an epidemiological analysis of
      preconception health.
AB  - BACKGROUND: Recently published preconception health guidelines promote maternal
      health, yet adherence to those guidelines has not been documented. We
      hypothesized that pregnant women engaged in a healthier lifestyle than
      nonpregnant women, although this may vary by pregnancy intention and birth
      control method. METHODS: We performed secondary analysis of cross-sectional data
      from the Behavioral Risk Factor Surveillance System (BRFSS) (2002 and 2004
      datasets). The data are collected in all 50 states, the District of Columbia,
      Puerto Rico, the U.S. Virgin Islands, and Guam through a telephone survey of
      350,000 adults annually. Subjects were a representative sample of
      noninstitutionalized, 18-44-year-old, fertile women (n = 66,152). Based on
      pregnancy risk, women were grouped into one of five categories: pregnant,
      intending pregnancy (IP), unintended pregnancy high risk (HR), moderate risk
      (MR), and low risk (LR). Logistic regression was used to estimate adjusted
      prevalence odds ratios (aPOR) and 95% confidence intervals (CI) for behavioral
      characteristics using pregnant women as the referent group. RESULTS: IP, HR, MR,
      and LR women were more likely to drink any alcohol (aPOR 10.85, aPOR 8.39, aPOR
      11.90, aPOR 11.98, respectively), binge drink (aPOR 7.07, aPOR 6.24, aPOR 7.27,
      aPOR 7.17, respectively), heavy drink (aPOR 6.90, aPOR 5.67, aPOR 7.48, aPOR
      5.89, respectively), and smoke (aPOR 2.89, aPOR 2.69, aPOR 2.40, aPOR 2.09,
      respectively). Interestingly, IP, HR, MR, and LR women were more likely to engage
      in leisure activity (aPOR 1.37, aPOR 1.19, aPOR 1.57, aPOR 1.17, respectively).
      HR, MR, and LR women were less likely to consume folic acid (aPOR 0.14, aPOR
      0.21, aPOR 0.29, respectively), whereas women intending a pregnancy were equally
      likely to consume folic acid (aPOR 0.77 CI 0.30, 2.0), although the response rate
      for folic acid was low. CONCLUSIONS: Preconceptional health goals are not being
      met. Pregnancy risk, as delineated by contraceptive use, can inform interventions
      designed to prevent adversely exposed pregnancies.

PMID- 19105689
TI  - Lifetime interpersonal violence and self-reported chlamydia trachomatis diagnosis
      among California women.
AB  - OBJECTIVE: To examine the relationship between cumulative exposure to various
      types of interpersonal violence throughout the life span and self-reported
      history of Chlamydia trachomatis (CT) diagnosis in a population-based sample of
      California women. METHODS: This was a cross-sectional analysis of a population
      based survey of California women aged 18-44 years (n = 3521). Participants
      reported their experience of multiple types of interpersonal violence: physical
      or sexual abuse in childhood or adulthood and intimate partner violence (IPV) in
      the past 12 months. Current posttraumatic stress disorder (PTSD) and depressive
      symptoms were also reported. Separate logistic regression models assessed the
      association between experiencing each type of interpersonal violence, as well as
      women's cumulative exposure to violence, and past CT diagnosis, adjusting for
      age, race/ethnicity, and poverty, as well as mental health problems. RESULTS: Six
      percent of women reported a past diagnosis of CT, and 40.8% reported experiencing
      at least one type of interpersonal violence in their lifetime. All types of
      violence were significantly associated with higher odds of having a past CT
      diagnosis even after controlling for sociodemographics. Women who reported
      experiencing four or more types of violence experiences had over five times the
      odds of reporting a lifetime CT diagnosis compared with women who never
      experienced interpersonal violence (adjusted odds ratio = 5.71, 95% CI 3.27
      9.58). Current PTSD and depressive symptoms did not significantly affect the
      relationship between a woman's cumulative experience of violence and her risk of
      past CT diagnosis. CONCLUSIONS: There is a robust association between
      experiencing multiple forms of violence and having been diagnosed with CT. Women
      who seek treatment for sexually transmitted diseases (STDs), such as CT, should
      be assessed for their lifetime history of violence, especially violence in their
      current intimate relationships. Sexual risk reduction counseling may also be
      important for women who have a history of risky sexual behaviors and who are
      likely to be reinfected.

PMID- 19105690
TI  - Gender differences in HIV risk behaviors of inmates.
AB  - BACKGROUND: Incarcerated men and women differ in their views on HIV prevalence
      rates and susceptibility and their ability to prevent HIV infection. The
      objective of this study was to assess sex and gender differences in HIV risk
      behaviors of inmates in order to better support the consideration of gender in
      the development of HIV prevention interventions for the incarcerated population.
      METHODS: A survey of 1819 inmates was conducted using a structured questionnaire.
      Self-reported HIV risk behaviors of 526 women and 1293 men during incarceration
      were compared. Bivariate analyses were done to identify gender differences in
      demographic characteristics and HIV risk behaviors. Logistic regression was used
      to determine factors associated with engaging in sexual intercourse in prison.
      RESULTS: Mean age was higher for women than men (p = 0.05), and >50% of
      participants were African Americans. More women than men reported that they
      engaged in sexual intercourse (p < 0.001); however, men were more likely to
      report anal sex (p < 0.001). There were no sex differences in injection drug use.
      Women who identified as bisexual or lesbian, those who had been currently
      incarcerated for at least 1 year, and those who received tattoos in prison were
      more likely to report sexual intercourse. The only independent risk factor
      identified for men was being currently incarcerated for at least 7 years.
      CONCLUSIONS: There are gender differences in HIV risk behaviors of inmates during
      incarceration. The findings in this study suggest that inmates may benefit from
      gender-specific HIV interventions while incarcerated and in the community
      subsequent to release.

PMID- 19105691
TI  - Selective recognition of protein tetraserine motifs with a cell-permeable, pro
      fluorescent bis-boronic acid.
AB  - There is considerable interest in novel cell imaging tools that avoid the use of
      fluorescent proteins. One widely used class of such reagents are "pro
      fluorescent" biarsenical dyes such as FlAsH, ReAsH, CrAsH, and Cy3As. Despite
      their utility, biarsenicals are plagued by high background labeling and
      cytotoxicity and are challenging to apply in oxidizing cellular locale. Here we
      demonstrate that [(3-oxospiro[isobenzofuran-1(3H),9'-[9H]xanthene]-3',6'
      diyl)bis(iminomethylene-2,1-phenylene)]bis-(9CI), a rhodamine-derived bisboronic
      acid (RhoBo) described initially as a monosaccharide sensor, functions as a cell
      permeable, turn-on fluorescent sensor for tetraserine motifs in recombinant
      proteins. RhoBo binds peptides or proteins containing Ser-Ser-Pro-Gly-Ser-Ser
      with affinities in the nanomolar concentration range and prefers this sequence to
      simple monosaccharides by >10,000-fold. RhoBo fails to form fluorescent complexes
      with constituents of the mammalian cell surface, as judged by epifluorescent,
      confocal, and TIRF microscopy, but fluoresces brightly within the Ser-Ser-Pro-Gly
      Ser-Ser-rich cell interior. These results suggest that current efforts to
      identify optimal serine-rich sequences for RhoBo will allow it to function
      effectively as a selective small-molecule label for appropriately tagged proteins
      either upon or within living cells.

PMID- 19105693
TI  - Anisotropic electron transport properties in sumanene crystal.
AB  - The high electron mobility with large anisotropy was attained in the needle-like
      single crystal of sumanene, which was indicated by time-resolved microwave
      conductivity (TRMC) measurement.

PMID- 19105692
TI  - Maternal serum granulocyte colony-stimulating factor levels and spontaneous
      preterm birth.
AB  - OBJECTIVE: Preterm birth (PTB) remains a cause of substantial morbidity with an
      elusive etiology. Previous studies suggested an association of PTB with elevated
      serum levels of granulocyte colony-stimulating factor (G-CSF) at 28 weeks
      gestation. G-CSF, a hematopoietic cytokine, mediates the increase in leukocytes
      in pregnancy and may play a role in placentation. We evaluated the association
      between maternal serum G-CSF in the first and second trimesters and PTB. METHODS:
      Serum samples collected for the Collaborative Perinatal Project (CPP) from women
      with normal pregnancy (n = 394) and PTB (n = 31), defined as delivery before 37
      weeks gestation, were used to assess G-CSF levels. Linear regression was used to
      evaluate the relation of G-CSF with gestational age (GA) at birth. Logistic
      regression, conditional on GA at sample provision, was used to model the
      association between G-CSF and PTB. RESULTS: G-CSF was significantly associated
      with gestational age at birth (p = 0.02). In conditional logistic regression
      models, G-CSF was significantly associated with PTB, with an adjusted odds ratio
      (AOR) of 1.52 (95% confidence interval [CI] 1.07, 2.16) per standard deviation
      (SD) increase. CONCLUSIONS: Acute effects of G-CSF on PTB have been suggested. In
      our study we observed an association of higher serum G-CSF levels early in the
      second trimester with PTB, suggesting PTB as the culmination process beginning
      early in, if not before, pregnancy.

PMID- 19105695
TI  - Mesoscopic donor-acceptor multilayer by ultrahigh-vacuum codeposition of Zn
      tetraphenyl-porphyrin and C70.
AB  - The peculiar electrochemical and photophysical properties of porphyrin and
      fullerene molecules make them promising candidates for the construction of two-
      and three-dimensional organic-based materials. An important question is how
      pristine fullerene and porphyrin will organize when deposited on surfaces via in
      vacuum molecular beam evaporation. Here we show that codeposition of C(70) and Zn
      tetraphenyl-porphyrin (ZnTPP) induces the self-assembly of electron-rich flat
      aromatic molecules at the curved surface of C(70), thus enhancing the chromophore
      interaction and forming a supramolecular multilayer donor-acceptor structure.
      While the ground-state electronic spectra almost reflect a simple summation of
      ZnTPP and C(70) components, the excited-state electrons at the porphyrin
      macrocycle can rapidly delocalize to the fullerene. The excited charge transfer
      time scale is faster than 1-2 fs, as shown by resonant photoemission for the core
      excited charges.

PMID- 19105694
TI  - Gender risk of nonfatal stroke in type 2 diabetic patients differs depending on
      the type of treatment.
AB  - BACKGROUND: The gender differences in stroke risk among diabetic patients with
      different treatments have not been studied previously. We aim to determine if
      there is a gender difference in nonfatal stroke risk in diabetic patients
      receiving different types of glucose-lowering treatments. METHODS: In December
      2005, data of type 2 diabetic patients were extracted from a nationwide
      population-based diabetes registry covering 11 Ukrainian regions. Male/female
      odds ratios (OR) for nonfatal stroke were calculated in three treatment groups:
      diet only 7,273/15,901, oral glucose-lowering drugs 15,109/33,913, and insulin
      5,529/12,462 male/female. Male/female ORs of stroke were estimated using a
      logistic regression model. RESULTS: The age-adjusted ORs of stroke were higher
      among diabetic men compared with diabetic women with oral glucose-lowering drug
      treatment (OR 1.37, 95% CI 1.22-1.54) and diet treatment only (OR 1.53, 95% CI
      1.35-1.73). No differences were found among patients who used insulin (OR 0.97,
      95% CI 0.84-1.11). Further adjustment for duration of type 2 diabetes, body mass
      index (BMI), systolic blood pressure, total cholesterol, and smoking affected the
      results only slightly. CONCLUSIONS: The gender risks of nonfatal stroke in
      patients with type 2 diabetes appear to differ considerably depending on
      treatment types.

PMID- 19105696
TI  - Catalytic carbon-carbon sigma bond activation: an intramolecular carbo-acylation
      reaction with acylquinolines.
AB  - Carbon-carbon sigma-bond activation is a contemporary challenge for
      organometallic chemistry and catalysis. Herein, we disclose a new alkene
      carboacylation reaction initiated by quinoline-directed, rhodium-catalyzed C-C
      sigma bond activation. The alkene carboacylation allows for the construction of
      all-carbon quaternary centers, with a broad substrate scope, providing access to
      carbocyclic and heterocyclic ring systems in good to excellent yields.

PMID- 19105699
TI  - Self-assembly of colloids with liquid protrusions.
AB  - A facile and flexible synthesis for colloidal molecules with well-controlled
      shape and tunable patchiness is presented. Cross-linked polystyrene spheres with
      a liquid protrusion were found to assemble into colloidal molecules by
      coalescence of the liquid protrusions. Similarly, cross-linked poly(methyl
      methacrylate) particles carrying a wetting layer assembled into colloidal
      molecules by coalescence of the wetting layer. Driven by surface energy, a liquid
      droplet on which the solid spheres are attached is formed. Subsequent
      polymerization of the liquid yields a wide variety of colloidal molecules as well
      as colloidosomes with tunable patchiness. Precise control over the topology of
      the particles has been achieved by changing the amount and nature of the swelling
      monomer as well as the wetting angle between the liquid and the seed particles.
      The overall cluster size can be controlled by the seed size as well as the
      swelling ratio. Use of different swelling monomers and/or particles allows for
      chemical diversity of the patches and the center. For low swelling ratios
      assemblies of small numbers of seeds resemble clusters that minimize the second
      moment of the mass distribution. Assemblies comprised of a large number of
      colloids are similar to colloidosomes exhibiting elastic strain relief by scar
      formation.

PMID- 19105697
TI  - Anatomy of a simple acyl intermediate in enzyme catalysis: combined biophysical
      and modeling studies on ornithine acetyl transferase.
AB  - Acyl-enzyme complexes are intermediates in reactions catalyzed by many hydrolases
      and related enzymes which employ nucleophilic catalysis. However, most of the
      reported structural data on acyl-enzyme complexes has been acquired under
      noncatalytic conditions. Recent IR analyses have indicated that some acyl-enzyme
      complexes may be more flexible than most crystallographic analyses have implied.
      OAT2 is a member of the N-terminal nucleophile (Ntn) hydrolase enzyme superfamily
      and catalyzes the reversible transfer of an acetyl group between the alpha-amino
      groups of ornithine and glutamate in a mechanism proposed to involve an acyl
      enzyme complex. We have carried out biophysical analyses on ornithine acetyl
      transferase (OAT2), both in solution and in the crystalline state. Mass
      spectrometric studies identified Thr-181 as the residue acetylated during OAT2
      catalysis; (13)C NMR analyses implied the presence of an acyl-enzyme complex in
      solution. Crystallization of OAT2 in the presence of N-alpha-acetyl-L-glutamate
      led to a structure in which Thr-181 was acetylated; the carbonyl oxygen of the
      acyl-enzyme complex was located in an oxyanion hole and positioned to hydrogen
      bond with the backbone amide NH of Gly-112 and the alcohol of Thr-111. While the
      crystallographic analyses revealed only one structure, IR spectroscopy
      demonstrated the presence of two distinct acyl-enzyme complex structures with
      carbonyl stretching frequencies at 1691 and 1701 cm(-1). Modeling studies implied
      two possible acyl-enzyme complex structures, one of which correlates with that
      observed in the crystal structure and with the 1691 cm(-1) IR absorption. The
      second acyl-enzyme complex structure, which has only a single oxyanion hole
      hydrogen bond, is proposed to give rise to the 1701 cm(-1) IR absorption. The two
      acyl-enzyme complex structures can interconvert by movement of the Thr-111 side
      chain alcohol hydrogen away from the oxyanion hole to hydrogen bond with the
      backbone carbonyl of the acylated residue, Thr-181. Overall, the results reveal
      that acyl-enzyme complex structures may be more dynamic than previously thought
      and support the use of a comprehensive biophysical and modeling approach in
      studying such intermediates.

PMID- 19105700
TI  - Engineering of supramolecular H-bonded nanopolygons via self-assembly of
      programmed molecular modules.
AB  - Discrete and multicomponent nanoscale noncovalent assemblies on surfaces
      featuring polygonal porous domains are presented. The molecular engineering
      concept involves multivalent molecular modules that are preprogrammed to undergo
      heteromolecular recognition by exploiting complementary multiple H bonds. Two
      types of molecular modules have been engineered: (i) a linear unit of twofold
      symmetry exposing two 2,6-di(acylamino)pyridyl [donor-acceptor-donor (DAD)]
      recognition sites at its extremities with a 180 degree orientation relative to
      each other and (ii) an angular unit constituted by a 1,3,6,8-tetraethynylpyrene
      core peripherally functionalized with four uracil groups [acceptor-donor-acceptor
      (ADA)] positioned at 60 degrees and 120 degrees relative to each other. These
      molecular modules self-assemble through H-bonds between the complementary
      recognition sites, forming supramolecular architectures. Their symmetry depends
      upon the type of each individual subunit and the stoichiometry as well as on the
      combination and distribution of the main symmetry axes. These so-formed two
      dimensional (2D) supramolecular oligomers have been studied in solution by
      optical spectroscopy and on highly ordered pyrolitic graphite (HOPG) substrates
      by scanning tunneling microscopy (STM) at the solid-liquid interface. Steady
      state UV/vis absorption and emission titration measurements suggest the
      reversible formation of multiple oligomeric species with slightly modulated
      fluorescence spectra. This likely reflects the presence of various aggregates
      between the two polytopic receptors, which exhibit somewhat different electronic
      delocalization as a function of the aggregate size. The presence of multiple
      species is further confirmed by time-resolved luminescence measurements: lifetime
      values are fitted as double/multiple exponentials and are always shorter than 6.5
      ns. The formation of several oligomeric species is further supported by in situ
      STM measurements at the solid-liquid interface that provided evidence, with
      submolecular resolution, for the formation of multicomponent and discrete 2D
      polygon-like assemblies. We highlight the role of accurate control of the
      concentration required to image on the surface the 2D oligomeric species formed
      in solution, which allows us to bypass the determinant role of the substrate
      molecule interactions in forming the thermodynamically stable monocomponent
      architectures at the solid-liquid interface.

PMID- 19105701
TI  - Promises and challenges of human papillomavirus vaccines for cervical cancer.

PMID- 19105702
TI  - New developments in targeted molecular therapies for glioblastoma.

PMID- 19105704
TI  - Gefitinib for the treatment of non-small-cell lung cancer.
AB  - Gefitinib is an orally bioavailable, EGF receptor tyrosine kinase inhibitor and
      was the first targeted drug to be approved for non-small-cell lung cancer
      (NSCLC). Identification of objective tumor regressions with gefitinib in NSCLC
      patients has resulted in intense, worldwide clinical and basic research directed
      toward finding the optimal use of gefitinib in NSCLC. A recent large
      international Phase III study (IRESSA NSCLC Trial Evaluating Response and
      Survival Against Taxotere [INTEREST]) comparing gefitinib and docetaxel in
      unselected pretreated patients showed equivalent survival with better
      tolerability and quality of life. In addition, a Phase III study (WJTOG0203)
      evaluating gefitinib as sequential therapy after platinum-doublet chemotherapy
      showed the improved progression-free survival time. Furthermore, a large-scale
      randomized study (IRESSA Pan-Asia study [IPASS]) comparing gefitinib monotherapy
      with carboplatin/paclitaxel for previously untreated patients with adenocarcinoma
      who were never- or light-smokers showed an improved progression-free survival
      time in the gefitinib arm. A smaller Phase III study of pretreated Japanese
      patients (V-15-32) also demonstrated no difference in overall survival compared
      with docetaxel, with a statistically greater overall response rate. Somatic
      mutations in the EGFR gene, the target of gefitinib, were associated with
      dramatic and durable regressions in patients with NSCLC. Currently, investigators
      are trying to determine the optimal approach to select patients for treatment
      with gefitinib. This article aims to briefly summarize the profile of gefitinib,
      EGFR mutations, landmark trials with gefitinib and, also, ongoing trials that may
      herald an era of individualized therapy in at least some NSCLC patients.

PMID- 19105705
TI  - Anagrelide: 20 years later.
AB  - Thrombocytosis is a common feature of chronic myeloproliferative disorders (MPD)
      and may be asymptomatic or associated with transient microvascular vaso-occlusive
      symptoms or large vessel arterial or venous thrombosis. Failure of either the
      hematocrit or the platelet count to correlate with thrombotic events is a
      peculiar conundrum of the MPDs. Asymptomatic thrombocytosis in young MPD patients
      with no cardiovascular risk factors does not require treatment. It is also
      undisputed that lowering the platelet count reduces the incidence of
      microvascular events in MPD patients. At the same time, no study to date has
      demonstrated that platelet count reduction prolongs survival in MPD patients.
      Agents such as hydroxyurea, busulfan, IFN-alpha and anagrelide, have been used to
      reduce an elevated platelet count and decrease thrombohemorrhagic events in at
      risk patients with thrombocytosis associated with an MPD. When treatment is
      required, it makes sense to use drugs that are not myelotoxic or mutagenic. Based
      on the Primary Thrombocythaemia 1 study, hydroxyurea is the treatment of choice
      for thrombocytosis-associated transient ischemic attacks. However, hydroxyurea
      does not prevent venous thrombosis, is not more effective in preventing arterial
      thrombosis than anagrelide and its long-term safety is not established.
      Therefore, unless curative therapy is planned, one should use the least
      myelotoxic agent when platelet count reduction is required. In this regard,
      anagrelide can be considered a first-line drug. With regard to long-term safety
      of anagrelide, the EMEA has required close monitoring of the safety points
      identified in future Periodic Safety Update Reports and in a Post Authorisation
      Safety Study in the EU, which will focus especially on cardiovascular events and
      acute leukemia. In this article, we review anagrelide pharmacology, the
      physiology of thrombopoiesis, the differential diagnosis of thrombocytosis and
      the management of patients with an elevated platelet count.

PMID- 19105707
TI  - Extreme hypofractionation for prostate cancer.
AB  - In ideal circumstances the fractionation schedule of radiotherapy should match
      the fractionation sensitivity of the tumor relative to the nearby normal tissues.
      A number of recent publications have suggested that the alpha/beta ratio for
      prostate tumors is low - in the range of 1-3 Gy. In fact, if alpha/beta is low,
      then hypofractionated schedules using fewer, larger fractions should improve the
      therapeutic ratio. This critical article examines two methods that represent
      schedules at the extreme end of the fractionation spectrum (3-5 fractions): high
      dose-rate brachytherapy as monotherapy and stereotactic body radiotherapy.

PMID- 19105706
TI  - The NSABP Study of Tamoxifen and Raloxifene (STAR) trial.
AB  - In the Study of Tamoxifen and Raloxifene (STAR) trial, postmenopausal women at
      increased risk of breast cancer received either oral tamoxifen (20 mg/day) or
      raloxifene (60 mg/day) over 5 years. There were an equal number of cases of
      invasive breast cancer in women assigned to tamoxifen and raloxifene. There were
      fewer cases of noninvasive breast cancer in the tamoxifen group than in the
      raloxifene group (risk ratio [RR]: 1.40; 95% confidence interval [CI]: 0.98
      2.02). There were more cases of uterine cancer with tamoxifen than with
      raloxifene (RR: 0.62; 95% CI: 0.35-1.08). Thromboembolic events occurred less
      often in the raloxifene group (RR: 0.70; 95% CI: 0.54-0.91) and there were fewer
      cataracts and cataract surgeries in the women taking raloxifene (RR: 0.79; 95%
      CI: 0.68-0.92). The STAR trial has shown that raloxifene is as effective as
      tamoxifen in reducing the risk of invasive breast cancer and has a lower risk of
      adverse events but a nonstatistically significant higher risk of noninvasive
      breast cancer. The risk of other cancers, fractures, ischemic heart disease and
      stroke is similar for both drugs.

PMID- 19105708
TI  - Cancer vaccines: will we ever learn?
AB  - Scientists and clinicians engaged in developing therapeutic cancer vaccines
      cannot be anything other than troubled by the sheer number of Phase III clinical
      trial failures in the field. Are we inveterate optimists or do we have reason for
      continuing to plough our lonely furrow? In this perspective article, we answer
      why Phase III failures have been to the fore and highlight why the field should
      be optimistic given the knowledge gained from these pioneering studies and our
      improved understanding of how the immune system interacts with cancer.

PMID- 19105709
TI  - PET and PET-CT imaging of gynecological malignancies: present role and future
      promise.
AB  - In this article, we have reviewed the current role of PET/PET-computed tomography
      (CT) in the management of gynecological malignancies. The promise of this
      technique is becoming increasingly evident, based upon several studies conducted
      in these malignancies. 2-fluoro-2-deoxy-D-glucose-PET appears to have a potential
      role in assessing response to treatment and forecasting prognosis. For cervical
      carcinoma, the modality has proven useful in both the staging of untreated
      advanced cervical cancer and restaging of the disease. Its role in
      prognostication of the disease and in detecting lesions in the setting of post
      treatment unexplained tumor-marker elevation appears promising. PET is of great
      benefit as a diagnostic tool in ovarian carcinoma when there is an increase in
      serum CA-125 and CT/MRI or conventional imaging are inconclusive or negative.
      With regard to its role in endometrial carcinoma, its benefit is particularly
      emphasized in the setting of post-therapy surveillance of the disease, although,
      in a limited series, it also appears to give additional information in the
      pretreatment states. PET may be of value in detecting the extra-uterine lesions
      that are not visualized with CT/MRI. Data on the role of 2-fluoro-2-deoxy-D
      glucose-PET imaging in the management of vulvar and vaginal cancer are relatively
      sparse at this time but the modality appears to be of value in staging disease
      and is more effective than conventional diagnostic modalities with respect to
      detecting nodal metastasis in both malignancies.

PMID- 19105710
TI  - RNA-based immunotherapy of cancer: role and therapeutic implications of dendritic
      cells.
AB  - Cancer immunotherapy aims at eliciting an immune response directed against tumor
      antigens to help fight off residual tumor cells and, thereby, improve the
      survival and quality of life of cancer patients. Different immunotherapeutic
      approaches share the use of dendritic cells (DCs) to present tumor-associated
      antigens to T lymphocytes. DCs are specialized for antigen presentation, and
      their immunogenicity leads to the induction of antigen-specific immune responses.
      Ex vivo-generated DCs can be loaded with antigens and re-infused to the patients
      or they can be used for the ex vivo expansion of anti-tumor lymphocytes.
      Alternatively, methods exist to target antigens in vivo without the need for ex
      vivo cell manipulations. DCs loaded ex vivo with RNA can be administered safely
      and might prove to be an asset for producing antigen-specific immune responses.
      Furthermore, these observations have led to clinical trials designed to
      investigate the immunological and clinical effects of RNA-pulsed DCs administered
      as a therapeutic vaccine in cancer patients. However, selection of the antigen,
      methods for introducing tumor-associated antigens into MHC class I and II
      processing pathways, methods for isolation and activation of DCs and route of
      administration are the parameters to be considered for designing and conducting
      clinical trials with phenotypically altered DCs. The enhanced RNA transfection
      efficiency and DC maturation would further improve antigen processing and
      presentation and T-cell costimulation, resulting in the induction of heightened
      anti-tumor immune responses. Therefore, DCs pulsed with RNA continues to hold
      promise for cellular immunotherapy.

PMID- 19105711
TI  - New avenues for second-line treatment of metastatic non-small-cell lung cancer.
AB  - Platinum-based doublets are the standard first-line therapy for patients with
      advanced non-small-cell lung cancer, with approximately a third of patients
      obtaining an objective response with first-line chemotherapy and another 20-30%
      achieving temporary disease stabilization. However, all patients inevitably
      experience disease progression. Three agents are approved for treating patients
      who progress after one prior regimen: docetaxel, pemetrexed and erlotinib.
      Erlotinib is the only agent approved for use in the third-line setting. Although
      these agents have yielded similar outcomes in terms of anti-tumor activity and
      efficacy, they have different toxicity profiles, and some factors that can help
      in the choice among them have begun to emerge, such as smoking history and
      histotype. Several new molecularly targeted agents have shown activity in Phase
      II trials and may be integrated into second-line therapy as single agents or in
      combination with current agents in the future. In particular, the most
      encouraging data in this clinical setting have been reported with the
      antiangiogenetic drugs bevacizumab (already approved for use in the first-line
      setting), vandetanib and sunitinib. Phase III trials with these agents are
      ongoing.

PMID- 19105712
TI  - Intermittent therapy in the palliative treatment of metastatic colorectal cancer.
AB  - After nearly 40 years of treatment of metastatic colorectal cancer with 5
      fluorouracil (5-FU) or best supportive care, the treatment of this disease has
      evolved rapidly in the last decade. Treatment options now include several new
      cytotoxic and biologic agents. Combination regimens, such as folinic acid, 5-FU
      plus oxaliplatin (FOLFOX), and folinic acid, 5-FU plus irinotecan (FOLFIRI), have
      significantly improved clinical efficacy as related to response rates and overall
      survival. The optimum integration of chemotherapy regimens with biological agents
      targeting critical signaling pathways, such as, bevacizumab (monoclonal antibody
      targeting VEGF-A), cetuximab and panitumumab (monoclonal antibodies targeting the
      EGF receptor) are still under evaluation. With the availability of several
      treatment options, however, comes the issue of optimal duration of chemotherapy
      in order to achieve the dual goals of clinical efficacy and quality of life, and
      the issue of cost-effectiveness of treatment, particularly with the newer
      targeted therapies. One method of achieving this may be to accommodate planned
      treatment holidays so patients can recover from the physical and psychological
      side effects of their chemotherapy as long as clinical efficacy is not
      compromised. In this review, we discuss the evidence for the use of intermittent
      chemotherapy in metastatic colorectal cancer.

PMID- 19105713
TI  - Treatment of resectable gastric cancer: current standards of care.
AB  - Gastric cancer is the second leading cause of cancer death worldwide. The local
      surgical treatment of gastric cancer varies geographically. However, there has
      been a confluence of opinion regarding the optimal therapy of gastric cancer
      toward multimodality therapy. In the East, many clinicians pursue adjuvant
      chemotherapy after a D2 resection. However, in the West, clinicians use either
      perioperative chemotherapy or postoperative chemoradiation. It remains unclear at
      this time whether either perioperative approach is the optimal approach.

PMID- 19105716
TI  - Ferromagnetic disklike Mn(IV)Mn(II)3Na(I)3 heptanuclear complex with a S = 9
      ground state.
AB  - The wheel-shaped heptanuclear cluster complex
      {[Mn(4)Na(3)(thmp)(2)(acac)(6)(H(2)O)(6)]CH(3)COO} x 4 H(2)O is the first
      heterometallic mixed-valent disklike compound with apical alkali-metal ions. The
      weak ferromagnetic interaction between the central Mn(4+) ion and the peripheral
      Mn(2+) ones leads to a high-spin ground state (S = 9).

PMID- 19105714
TI  - Early development of sunitinib in hepatocellular carcinoma.
AB  - Sunitinib malate is an oral, multitargeted receptor tyrosine kinase inhibitor of
      VEGF receptors 1, 2 and 3; PDGF receptors alpha and beta, and other receptor
      tyrosine kinases implicated in tumor growth, angiogenesis and metastasis.
      Hepatocellular carcinoma (HCC) is a highly vascular tumor that overexpresses
      several angiogenic factors; VEGF and PDGF signaling pathways play a key role in
      HCC. Until recently, treatment options for advanced HCC were limited and
      conventional therapies have met with poor response rates. Sorafenib provided
      proof-of-concept for molecularly targeted therapy in advanced HCC and has
      recently been approved for treatment. However, not all patients can tolerate
      sorafenib and patients may experience tumor progression; therefore, additional
      treatment options are warranted. Sunitinib has shown early evidence of anti-tumor
      activity in Phase II trials in US, European and Asian patients with locally
      advanced, unresectable and metastatic HCC. A Phase III trial of sunitinib in HCC
      is ongoing.

PMID- 19105717
TI  - Straightforward protein immobilization using redox-initiated poly(methyl
      methacrylate) polymerization.
AB  - Rigid poly(methyl methacrylate) (PMMA) biochips directly modified with active
      protein spots were obtained, using a redox-initiated PMMA polymerization process.
      The protein immobilization mechanism is believed to be a combination of both a
      covalent binding through transient amino acid radical generation and a direct
      entrapment of the biomolecules in the PMMA polymer. Three different immunoassays
      (binding, capture, and sandwich) were performed using the developed system, and
      really promising limits of detection (160-200pg/mL) were obtained, demonstrating
      a novel straightforward route to fabricate plastic biochips.

PMID- 19105718
TI  - Synthesis and colloidal properties of polyether-magnetite complexes in water and
      phosphate-buffered saline.
AB  - Biocompatible magnetic nanoparticles show great promise for many biotechnological
      applications. This paper addresses the synthesis and characterization of
      magnetite nanoparticles coated with poly(ethylene oxide) (PEO) homopolymers and
      amphiphilic poly(propylene oxide-b-ethylene oxide) (PPO-b-PEO) copolymers that
      were anchored through ammonium ions. Predictions and experimental measurements of
      the colloidal properties of these nanoparticles in water and phosphate-buffered
      saline (PBS) as functions of the polymer block lengths and polymer loading are
      reported. The complexes were found to exist as primary particles at high polymer
      compositions, and most formed small clusters with equilibrium sizes as the
      polymer loading was reduced. Through implementation of a polymer brush model, the
      size distributions from dynamic light scattering (DLS) were compared to those
      from the model. For complexes that did not cluster, the experimental sizes
      matched the model well. For complexes that clustered, equilibrium diameters were
      predicted accurately through an empirical fit derived from DLS data and the half
      life for doublet formation calculated using the modified Derjaguin-Landau-Verwey
      Overbeek (DLVO) theory. Deviation from this empirical fit provided insight into
      possible additional interparticle hydrophobic interactions for select complexes
      for which the DLVO theory could not account. While the polymers remained bound to
      the nanoparticles in water, most of them desorbed slowly in PBS. Desorption was
      slowed significantly at high polymer chain densities and with hydrophobic PPO
      anchor blocks. By tailoring the PPO block length and the number of polymer chains
      on the surface, flocculation of the magnetite complexes in PBS was avoided. This
      allows for in vitro experiments where appreciable flocculation or sedimentation
      will not take place within the specified time scale requirements of an
      experiment.

PMID- 19105719
TI  - Microfluidic droplet method for nucleation kinetics measurements.
AB  - In this work, we developed a microfluidic equivalent of the classical droplet
      method for investigating nucleation kinetics. Our microfluidic device allows us
      to store hundreds of droplets of small volume ( approximately 100 nL) and to
      accurately control their temperature. We also monitor directly all the stored
      droplets, and thus perform statistical measurements on a large number of
      nucleation events. In the case of aqueous solutions of potassium nitrate, we
      manage to investigate nucleation kinetics and polymorphs and quantify the
      influence of impurities. The use of small droplets is crucial in such
      experiments, since it allows the sample to reach high supersaturations and to
      separate all the nucleation events. Moreover, we compare our results to the
      classical nucleation theory, and we demonstrate unambiguously using direct
      observations of the droplets that nucleation in aqueous solutions of potassium
      nitrate always occurs using heterogeneous mechanisms.

PMID- 19105720
TI  - Synthesis and properties of methacrylic-functionalized tween monomer networks.
AB  - Tween surfactants possess very interesting properties such as biodegradability,
      biocompatibility, and low toxicity. The synthesis of acrylate monomers by means
      of the chemical modification of polysorbate surfactants Tween 20, 40, and 60 with
      unsaturated groups is described. Monomers were obtained as a result of the
      reaction of methacrylic anhydride with different grades of Tween surfactants.
      Further polymerization was carried out in tetrahydrofuran, dimethylformamide, and
      a mixture of water-tetrahydrofuran. Physicochemistry properties of the polymer
      networks were investigated, and the obtained results reveal that they strongly
      depend on the type of solvent used during the polymerization, as well as on the
      concentration of the casting solution. In particular, our study demonstrated
      that, depending on the solvent boiling point, i.e., the facility to remove the
      solvent from the polymer matrix, it is possible to predict properties of the
      network morphology. Moreover, in vitro studies on controlled release were
      accomplished to demonstrate the possibility of utilizing these new materials as
      drug delivery systems. All resulting networks represent a novel class of cross
      linked polymeric materials useful both in pharmaceutical and chemical
      applications.

PMID- 19105721
TI  - Effect of chemical permeation enhancers on nerve blockade.
AB  - Chemical permeation enhancers (CPEs) have the potential to improve access of
      local anesthetics to the nerve, thereby improving nerve block performance. We
      assessed the effects of six CPEs on nerve blockade from tetrodotoxin (TTX) and
      from bupivacaine. Each of the six surfactants, representing three CPE subgroups
      (anionic, cationic, and nonionic surfactants) was coinjected with TTX or
      bupivacaine at the sciatic nerve of Sprague-Dawley rats. Myotoxicity of CPEs,
      alone and with TTX, was assessed in vitro in C2C12 myotubes and in vivo via
      histological analysis. All enhancers produced marked concentration-dependent
      improvements in the frequency and duration of block with TTX but not bupivacaine.
      An in vitro toxicity assay showed a wide range of CPE myotoxicity, but in vivo
      histological assessment showed no signs of muscle or nerve damage at
      concentrations of CPEs that produced a half-maximal increase in the duration of
      block of TTX (except in the case of the cationic surfactant DDAB). This study
      demonstrates that CPEs can provide marked prolongation of nerve blockade from TTX
      but not bupivacaine, without apparent local tissue toxicity. These results may
      enhance the clinical applicability of TTX for prolonged-duration local
      anesthesia.

PMID- 19105723
TI  - Distributed Drug Discovery, Part 3: using D(3) methodology to synthesize analogs
      of an anti-melanoma compound.
AB  - For the successful implementation of Distributed Drug Discovery (D(3)) (outlined
      in the accompanying Perspective), students, in the course of their educational
      laboratories, must be able to reproducibly make new, high quality, molecules with
      potential for biological activity. This article reports the successful
      achievement of this goal. Using previously rehearsed alkylating agents, students
      in a second semester organic chemistry laboratory performed a solid-phase
      combinatorial chemistry experiment in which they made 38 new analogs of the most
      potent member of a class of antimelanoma compounds. All compounds were made in
      duplicate, purified by silica gel chromatography, and characterized by NMR and
      LC/MS. As a continuing part of the Distributed Drug Discovery program, a virtual
      D(3) catalog based on this work was then enumerated and is made freely available
      to the global scientific community.

PMID- 19105722
TI  - Knocking down breast cancer resistance protein (Bcrp) by adenoviral vector
      mediated RNA interference (RNAi) in sandwich-cultured rat hepatocytes: a novel
      tool to assess the contribution of Bcrp to drug biliary excretion.
AB  - BCRP transports numerous drugs/derived metabolites and toxins, and exhibits
      overlapping substrate specificity with P-glycoprotein (P-gp) and multidrug
      resistance-associated protein 2 (MRP2). Assessing the contribution of BCRP to
      drug/metabolite biliary excretion in intact hepatocytes remains a challenge.
      Current studies were designed to develop a novel in vitro tool to specifically
      assess the contribution of Bcrp to drug biliary excretion. Adenoviral vectors
      expressing short hairpin (sh) RNA targeting Bcrp (Ad-si01Bcrp) or a nontarget
      control (Ad-siNT) were packaged and infected into sandwich-cultured rat
      hepatocytes (SCRH). Protein levels were detected by immunoblot. Biliary excretion
      index (BEI) and in vitro biliary clearance (Cl(biliary)) of nitrofurantoin (BCRP
      substrate) and digoxin (P-gp substrate) were compared among noninfected, Ad-siNT-
      and Ad-si01Bcrp-infected SCRH. shRNA targeting Bcrp efficiently knocked down Bcrp
      in SCRH, while levels of other transport proteins (P-gp, Mrp2, Bsep, Mrp4 and
      Oatp1a1) were unaffected. In SCRH exhibiting Bcrp knockdown, cellular
      accumulation of nitrofurantoin was increased markedly and nitrofurantoin BEI and
      in vitro Cl(biliary) were decreased to 11% and 14% of control, respectively.
      Digoxin values were unaffected by knockdown of Bcrp. Results indicated that Bcrp
      in SCRH contributed predominantly to nitrofurantoin biliary excretion, but played
      a negligible role in digoxin biliary excretion. In summary, Bcrp knockdown in
      SCRH is the first in vitro model utilizing intact hepatocytes to assess the
      contribution of Bcrp to the biliary excretion of drugs. This approach may be
      useful in predicting drug-drug interactions in biliary excretion and the
      consequence of impaired BCRP function on the hepatic exposure of drugs/derived
      metabolites.

PMID- 19105728
TI  - Curved microwell arrays created by diffusion-limited chemical etching of
      artificially engineered solids.
AB  - A new method based on diffusion-limited chemical etching has been developed for
      the productions of ordered arrays of curved microwells. Fiber-drawing
      nanomanufacturing is used to make ordered glass composites with controlled
      structure and composition. The differential chemical etching of two glasses in
      the composite preferentially etches one glass material away and generates ordered
      microwell arrays. The microwells can be replicated onto polymer films to form
      microdome arrays. Monte Carlo simulation illustrates the diffusion-controlled
      etching process. The etched microwells have been used to prepare
      micro/nanocrystals of proteins and inorganic materials with controlled sizes.

PMID- 19105724
TI  - Distributed Drug Discovery, Part 1: linking academia and combinatorial chemistry
      to find drug leads for developing world diseases.

PMID- 19105729
TI  - Determining the highly anisotropic cell structures of Pinus sylvestris in three
      orthogonal directions by PGSTE NMR of absorbed water and methane.
AB  - The walls of solid matrix restrict the self-diffusion of a fluid absorbed in the
      matrix, and this is reflected in the echo amplitudes measured by PGSTE NMR.
      Hence, the pore size distribution of the matrix can be extracted from the echo
      amplitudes. We demonstrate that, when both liquids and gases (water and methane
      in this case) are used as probe fluids, the scale of the dimensions observable by
      PGSTE NMR may be over 4 orders of magnitude. This enables determining the
      dimensions of highly anisotropic pores. In the present case, the wood cell
      structures of Pinus sylvestris in three orthogonal directions were studied.

PMID- 19105725
TI  - Distributed Drug Discovery, Part 2: global rehearsal of alkylating agents for the
      synthesis of resin-bound unnatural amino acids and virtual D(3) catalog
      construction.
AB  - Distributed Drug Discovery (D(3)) proposes solving large drug discovery problems
      by breaking them into smaller units for processing at multiple sites. A key
      component of the synthetic and computational stages of D(3) is the global
      rehearsal of prospective reagents and their subsequent use in the creation of
      virtual catalogs of molecules accessible by simple, inexpensive combinatorial
      chemistry. The first section of this article documents the feasibility of the
      synthetic component of Distributed Drug Discovery. Twenty-four alkylating agents
      were rehearsed in the United States, Poland, Russia, and Spain, for their utility
      in the synthesis of resin-bound unnatural amino acids 1, key intermediates in
      many combinatorial chemistry procedures. This global reagent rehearsal, coupled
      to virtual library generation, increases the likelihood that any member of that
      virtual library can be made. It facilitates the realistic integration of
      worldwide virtual D(3) catalog computational analysis with synthesis. The second
      part of this article describes the creation of the first virtual D(3) catalog. It
      reports the enumeration of 24,416 acylated unnatural amino acids 5, assembled
      from lists of either rehearsed or well-precedented alkylating and acylating
      reagents, and describes how the resulting catalog can be freely accessed,
      searched, and downloaded by the scientific community.

PMID- 19105730
TI  - Yields of beta-hydroxynitrates and dihydroxynitrates in aerosol formed from OH
      radical-initiated reactions of linear alkenes in the presence of NO(x).
AB  - Yields of beta-hydroxynitrates and dihydroxynitrates in aerosol formed from OH
      radical-initiated reactions of linear C(8)-C(17) 1-alkenes and C(14)-C(17)
      internal alkenes in the presence of NO(x) were measured using a thermal
      desorption particle beam mass spectrometer coupled to a high-performance liquid
      chromatograph (HPLC) with UV-vis detector for identification and quantification.
      For 1-alkenes, total yields of beta-hydroxynitrates normalized for OH radical
      addition to the CC double bond increased with carbon number, primarily because of
      enhanced gas-to-particle partitioning, to a plateau of 0.140 +/- 0.009 in the
      C(14)-C(17) range, with 1-hydroxy/2-hydroxy isomer fractions of 0.7:0.3. When
      combined with yields measured by O'Brien et al. ( O'Brien , J. M. , Czuba , E. ,
      Hastie , D. R. , Francisco , J. S. , and Shepson , P. S. J. Phys. Chem. A 1998 ,
      102 , 8903 ) for reactions of smaller alkenes, the results for both 1-alkenes and
      internal alkenes indicate that the branching ratios for the formation of beta
      hydroxynitrates from the reactions of NO with beta-hydroxyperoxy radicals
      (averaged over both isomers) increase from 0.009 for C(2) up to 0.13-0.15 for
      C(14) and larger and are approximately half the values determined by Arey et al.
      ( Arey , J. , Aschmann , S. M. , Kwok , E. S. C. , and Atkinson , R. J. Phys.
      Chem. A 2001 , 105 , 1020 ) for the corresponding alkyl peroxy radicals. The
      range of branching ratios may be higher for individual isomers, but this could
      not be determined. It is estimated that for 1-alkenes, approximately 60-70% of OH
      radical addition occurred at the terminal carbon atom. Average yields of
      dihydroxynitrates normalized for OH radical addition were 0.039 +/- 0.006 and
      0.006 +/- 0.002 for 1-alkenes and internal alkenes, with differences reflecting
      enhanced decomposition of beta-hydroxyalkoxy radicals formed from internal
      alkenes. The addition of NH(3) reduced yields significantly, apparently by
      altering hydrogen bonding between hydroxy and peroxy groups in hydroxyperoxy
      radical-NO complexes, whereas adding H(2)O had no obvious effect.

PMID- 19105731
TI  - Sharpening the toolbox of computational chemistry: a new approximation of
      critical f-values for multiple linear regression.
AB  - Multiple linear regression is a major tool in computational chemistry. Although
      it has been used for more than 30 years, it has only recently been noted within
      the cheminformatics community that the standard F-values used to assess the
      significance of the resulting models are inappropriate in situations where the
      variables included in a model are chosen from a large pool of descriptors, due to
      an effect known in the statistical literature as selection bias. We have used
      Monte Carlo simulations to estimate the critical F-values for many combinations
      of sample size (n), model size (p), and descriptor pool size (k), using stepwise
      regression, one of the methods most commonly used to derive linear models from
      large sets of molecular descriptors. The values of n, p, and k represent cases
      appropriate to contemporary cheminformatics data sets. A formula for general n,
      p, and k values has been developed from the numerical estimates that approximates
      the critical stepwise F-values at 90%, 95%, and 99% significance levels. This
      approximation reproduces both the original simulated values and an interpolation
      test set (within the range of the training values) with an R2 value greater than
      0.995. For an extrapolation test set of cases outside the range of the training
      set, the approximation produced an R2 above 0.93.

PMID- 19105732
TI  - Molecular recognition in biomolecules studied by statistical-mechanical integral
      equation theory of liquids.
AB  - Recent progress in the theory of molecular recognition in biomolecules is
      reviewed, which has been made based on the statistical mechanics of liquids or
      the RISM/3D-RISM theory during the last five years in the authors' group. The
      method requires just the structure of protein and the potential energy parameters
      for the biomolecules and solutions as inputs. The calculation is carried out in
      two steps. The first step is to obtain the pair correlation functions for
      solutions consisting of water and ligands based on the RISM theory. Then, given
      the pair correlation functions prepared in the first step, we calculate the 3D
      distribution functions of water and ligands around and inside protein based on
      the 3D-RISM theory. The molecular recognition of a ligand by the protein is
      realized by the 3D-distribution functions: if one finds some conspicuous peaks in
      the distribution of a ligand inside protein, then the ligand is regarded as
      "recognized" by the protein. Some biochemical processes are investigated, which
      are intimately related to the molecular recognition of small ligands including
      water, noble gases, and ions by a protein.

PMID- 19105733
TI  - An immobilized ortho-palladated dimethylbenzylamine complex as an efficient
      catalyst for the methanolysis of phosphorothionate pesticides.
AB  - The methanolysis of a series of P=S phosphorothionate pesticides (fenitrothion,
      coumaphos, diazinon, and dichlofenthion) catalyzed by an ortho-palladated complex
      covalently attached to two different solid supports, macroporous polystyrene and
      amorphous silica gel, was studied. Both the polystyrene and the silica-based
      catalysts showed excellent activity in methanol near neutral pH (neutral s(s)pH =
      8.38) at ambient temperature. These heterogeneous catalysts can be readily
      recovered and reused without significant loss of activity. Fifty milligrams of
      the silica-supported catalyst SiPd1 offered an acceleration of up to 8.6 x 10(9)
      fold for the methanolysis of fenitrothion (2) over the methoxide-promoted
      background reaction at s(s)pH = 8.8. For the same reaction, 50 mg of polystyrene
      supported complex PSPd2 provided a 3.7 x 10(9)-fold acceleration at s(s)pH = 8.8.
      When accounting for the amount of palladium in the solid, the slight superiority
      of silica over polystyrene as a solid support is believed to be a result of
      several possible factors including a higher concentration of active sites
      accessible to the reaction solvent and a more hydrophilic surface environment
      that allows better interaction of the methanol solvent with the attached
      palladacycle. Unlike the behavior in homogeneous solution, the rate of
      methanolysis of the substrates catalyzed by the solid catalysts was relatively
      insensitive to the nature of the substrate, probably indicating that a mass
      transport process is rate limiting. The solid-supported materials effectively
      decompose malathion at roughly stoichiometric ratios, but they are strongly
      inhibited by the thiol product resulting from the cleavage of the P=S(SR)
      linkage.

PMID- 19105734
TI  - Supersilylated tetraphosphene derivatives M2[t-Bu3SiPPPPSi-t-Bu3] (M = Li, Na,
      Rb, Cs) and Ba[t-Bu3SiPPPPSi-t-Bu3]: reactivity and cis-trans isomerization.
AB  - The tetraphosphenediides M2[t-Bu3SiPPPPSi-t-Bu3] (M = Li, Na, K) were accessible
      by the reaction of P4 with the silanides M[Si-t-Bu3] (M = Li, Na, K), whereas
      M2[t-Bu3SiPPPPSi-t-Bu3] (M = Rb, Cs) were obtained from the reaction of RbCl and
      CsF with Na2[t-Bu3SiPPPPSi-t-Bu3]. 31P NMR experiments revealed that, in
      tetrahydrofuran, Na2[t-Bu3SiPPPPSi-t-Bu3] adopts a cis configuration. However,
      treatment of Na2[t-Bu3SiPPPPSi-t-Bu3] with 18-crown-6 led to the formation of
      [Na(18-crown-6)(thf)2]2[t-Bu3SiPPPPSi-t-Bu3] that possesses a trans configuration
      in the solid state. The ion-separated tetraphosphenediide [Na(18-crown
      6)(thf)2]2[t-Bu3SiPPPPSi-t-Bu3] was analyzed using X-ray crystallography
      (monoclinic, space group P2(1)/n). The reaction of Na2[t-Bu3SiPPPPSi-t-Bu3] with
      BaI2 gave, conveniently, the corresponding barium derivative Ba[t-Bu3SiPPPPSi-t
      Bu3]. However, addition of AuI to the tetraphosphenediide Na2[t-Bu3SiPPPPSi-t
      Bu3] yielded 1,3-diiodo-2,4-disupersilyl-cyclotetraphosphane (monoclinic, space
      group C2/c), which is an isomer of disupersilylated diiodotetraphosphene. A
      further isomeric derivative of disupersilylated tetraphosphene, the 3,5
      disupersilyl-2,2-di-tert-butyl-2-stanna-bicyclo[2.1.0(1,4)]pentaphosphane, which
      possesses a phosphanylcyclotriphosphane structure, was obtained by the reaction
      of Na2[t-Bu3SiPPPPSi-t-Bu3] with t-Bu2SnCl2. Calculations revealed that the
      acyclic cis and trans isomers of the dianions [HPPPPH]2- and [H3SiPPPPSiH3]2- are
      thermodynamically more stable than the cyclic isomers with a
      phosphanylcyclotriphosphane or a cyclotetraphosphane structure. However, the
      neutral cyclic isomers of H4P4 and H2(H3Si)2P4 represent more stable structures
      than the cis- and trans-tetraphosphenes H2P-P=P-PH2 and (H3Si)HP-P=P-PH(SiH3),
      respectively. In addition, the molecular orbitals (MOs) of the silylated cis- and
      trans-tetraphosphene dianions of [H3SiPPPPSiH3]2-, which are comparable with
      those of the ion-separated supersilylated tetraphosphenediide [t-Bu3SiPPPPSi-t
      Bu3]2-, show the highest occupied antibonding pi*MO (HOMO). The HOMO is
      represented by the (p(z)-p(z)+p(z)-p(z)) pi* MO.

PMID- 19105735
TI  - Scope of the Suzuki-Miyaura cross-coupling reactions of potassium
      heteroaryltrifluoroborates.
AB  - A wide variety of bench-stable potassium heteroaryltrifluoroborates were
      prepared, and general reaction conditions were developed for their cross-coupling
      to aryl and heteroaryl halides. The cross-coupled products were obtained in good
      to excellent yields. This method represents an efficient and facile installation
      of heterocyclic building blocks onto preexisting organic substructures.

PMID- 19105736
TI  - Chelation-assisted carbon-halogen bond activation by a rhodium(I) complex.
AB  - Chelation-assisted activation of C-X bonds (X = Cl, Br, and I) took place in the
      reaction of [Rh(PPh(3))(2)(acetone)(2)](+) and 2-(2-halophenyl)pyridine or 10
      halobenzo[h]quinoline. A series of 16-electron five-coordinate cationic
      rhodium(III) monohalide complexes was synthesized at room temperature. Neutral
      octahedral rhodium(III) dihalide complexes were obtained when the corresponding
      cationic monohalide complexes were further heated in acetone. Rhodium and iridium
      diiodides with these cyclometalation motifs could be alternatively synthesized
      from the reaction of the corresponding cyclometalated hydride complexes and I(2).
      X-ray crystal structures of representative monohalide and dihalide complexes are
      reported. Octahedral rhodium(III) dihalide complexes are active catalysts for the
      dimerization of terminal alkynes, while 16-electron cationic rhodium(III)
      monohalides are inactive.

PMID- 19105737
TI  - Ultrasmooth silver thin films deposited with a germanium nucleation layer.
AB  - We demonstrate an effective method for depositing smooth silver (Ag) films on
      SiO(2)/Si(100) substrates using a thin seed layer of evaporated germanium (Ge).
      The deposited Ag films exhibit smaller root-mean-square surface roughness,
      narrower peak-to-valley surface topological height distribution, smaller grain
      size distribution, and smaller sheet resistance in comparison to those of Ag
      films directly deposited on SiO(2)/Si(100) substrates. Optically thin (
      approximately 10-20 nm) Ag films deposited with approximately 1-2 nm Ge
      nucleation layers show more than an order of magnitude improvement in the surface
      roughness. The presence of the thin layer of Ge changes the growth kinetics
      (nucleation and evolution) of the electron-beam-evaporated Ag, leading to Ag
      films with smooth surface morphology and high electrical conductivity. The
      demonstrated Ag thin films are very promising for large-scale applications as
      molecular anchors, optical metamaterials, plasmonic devices, and several areas of
      nanophotonics.

PMID- 19105738
TI  - Layer-by-layer deposition of polyelectrolyte-polyelectrolyte complexes for
      multilayer film fabrication.
AB  - Positively charged poly(allylamine hydrochloride) (PAH) and poly(acrylic acid)
      (PAA) complexes (noted as PAH-PAA) with a molar excess of PAH were layer-by-layer
      (LbL) assembled with polyanion poly(sodium 4-styrenesulfonate) (PSS) to produce
      multilayer films. The film structure and deposition behavior of the PAH-PAA/PSS
      films were influenced by the structure of PAH-PAA complexes in solution. For the
      PAH-PAA complexes with a low ratio of PAA to PAH the PAH-PAA complexes have low
      level cross-linking and are flexible. The resultant PAH-PAA/PSS films have a thin
      film thickness and smooth surface and exhibit a nonlinear deposition behavior
      where the amount of PAH-PAA complexes and PSS deposited in each deposition cycle
      are larger than in its previous cycle. The PAH-PAA complexes with a high ratio of
      PAA to PAH have high-level cross-linking and are rigid. The PAH-PAA/PSS films
      constructed from the rigid PAH-PAA complexes have a large film thickness and
      rough surface and exhibit a linear deposition behavior. Deposition of the PAH
      PAA/PSS films was well characterized by quartz crystal microbalance, atomic force
      microscopy, and scanning electron microscopy. The thermally cross-linked PAH
      PAA/PSS films can be released from substrate to form stable free-standing films
      by an ion-triggered exfoliation method. Meanwhile, positively charged PAH-PAA
      complexes can be LbL assembled with negatively charged PAH-PAA complexes with a
      molar excess of PAA to produce multilayer films. Use of polyelectrolyte
      polyelectrolyte complexes as building blocks for LbL fabrication provides a
      facile way to tailor the structures of the resultant films by simply changing the
      structure of the complexes in solution.

PMID- 19105739
TI  - A linear chain of water molecules accommodated in a macrocyclic nanotube channel.
AB  - A macrocyclic tetramer of 2-phenyl-1,3,4-oxadiazole was synthesized, and its self
      assembly was investigated. The macrocycle was stacked to form a one-dimensional
      (1D) columnar structure containing water molecules. The nanotube self-assembled
      into a bundle, which grew into a molecular wire. The association of the water
      molecules in the tubular cavity resulted in shielding of the 1D chain of water
      molecules by the nanotube; these macrocyclic nanotube channels are promising
      candidates for nanotechnological applications.

PMID- 19105740
TI  - Thermophoretic motion of water nanodroplets confined inside carbon nanotubes.
AB  - We study the thermophoretic motion of water nanodroplets confined inside carbon
      nanotubes using molecular dynamics simulations. We find that the nanodroplets
      move in the direction opposite the imposed thermal gradient with a terminal
      velocity that is linearly proportional to the gradient. The translational motion
      is associated with a solid body rotation of the water nanodroplet coinciding with
      the helical symmetry of the carbon nanotube. The thermal diffusion displays a
      weak dependence on the wetting of the water-carbon nanotube interface. We
      introduce the use of the moment scaling spectrum (MSS) in order to determine the
      characteristics of the motion of the nanoparticles inside the carbon nanotube.
      The MSS indicates that affinity of the nanodroplet with the walls of the carbon
      nanotubes is important for the isothermal diffusion and hence for the Soret
      coefficient of the system.

PMID- 19105741
TI  - A guanidinium ion-based anion- and solvent polarity-controllable molecular
      switch.
AB  - The macrocycle bis-p-xylyl[26]crown-6 (BPX26C6) is capable of complexing
      guanidinium ions in a [2]pseudorotaxane-like manner in solution. A corresponding
      molecular switch can be operated through changes in solvent polarity or the
      addition and removal of halogen and acetate anions.

PMID- 19105744
TI  - Strategy for the stereochemical assignment of tris-heteroleptic Ru(II) complexes
      by NMR spectroscopy.
AB  - The relative stereochemistry of tris-heteroleptic ruthenium complexes
      [Ru(pp)(pp')(pp'')](PF(6))(2), where pp = 1,10-phenanthroline-4-carboxamide, pp'
      = 5,6-dimethyl-1,10-phenanthroline, and pp'' = 7,8-dimethyl dipyrido[3,2-a:2',3'
      c]phenazine, was studied using NMR spectroscopy. The (1)H and (13)C spectra were
      assigned by using double-quantum-filtered correlation spectroscopy (DQF-COSY),
      heteronuclear single-quantum correlation (HSQC), and heteronuclear multiple-bond
      correlation (HMBC) experiments for the two diastereomers, each a pair of
      enantiomers. Nuclear Overhauser effect contacts between the neighboring ligands
      differentiated the two halves of each symmetrical ligand, thus enabling a full
      assignment of the NMR signals and an accurate determination of the relative
      stereochemistry of the complexes. The introduction of an additional chiral center
      to ligand pp by coupling it with L-lysine caused removal of the enantiomerism.
      Thus, four diastereomers were observed and their relative stereochemistry
      determined.

PMID- 19105745
TI  - Hierarchical assemblies of gold nanoparticles at the surface of a film formed by
      a bridged silsesquioxane containing pendant dodecyl chains.
AB  - Hierarchical aggregates of gold nanoparticles (NPs) on different length scales
      were in situ generated at the surface of a bridged silsesquioxane during the
      process of film formation by polycondensation and solvent evaporation. A
      precursor of a bridged silsesquioxane based on the reaction product of
      (glycidoxypropyl)trimethoxysilane (2 mol) with dodecylamine (1 mol) was
      hydrolytically condensed in a THF solution at room temperature in the presence of
      formic acid, water, and variable amounts of dodecanethiol-stabilized gold NPs
      (average diameter of 2 nm). The initial compatibility of the precursor with gold
      NPs was achieved by the presence of dodecyl chains in both components. Phase
      separation of gold NPs accompanied by partitioning to the air-polymer interface
      took place driven by the polycondensation reaction and solvent evaporation. A
      hierarchical organization of gold NPs in the structures generated at the air
      polymer interface was observed. Small body-centered cubic (bcc) crystals of about
      20 nm diameter were formed in the first step, in which the 2 nm gold NPs kept
      their individuality (high-resolution transmission electron microscopy, field
      emission scanning electron microscopy, and small-angle X-ray diffraction). In the
      second step, bcc crystals aggregated, forming compact micrometer-sized spherical
      particles. Under particular evaporation rates a third step of the self-assembly
      process was observed where micrometer-sized particles formed fractal structures.
      Increasing the initial concentration of gold NPs in the formulation led to more
      compact fractal structures in agreement with theoretical simulations. The surface
      percolation of NPs in fractal structures can be the basis of useful applications.

PMID- 19105746
TI  - Manipulating surface diffusion ability of single molecules by scanning tunneling
      microscopy.
AB  - The bonding of single diferrocene [Fc(CH(2))(14)Fc, Fc = ferrocenyl] molecules on
      a metal surface can be enhanced by partial decomposition of Fc groups induced by
      the tunneling current in scanning tunneling microscopy. Although the isolated
      intact molecule is mobile on the terrace of Cu(110) at 78 K, the modified
      molecule is immobilized on the terrace. Calculations based on density functional
      theory indicate that the hollow site of the Cu(110) surface is the energetically
      favorable adsorption site for both ferrocene and the Fe-cyclopentadienyl complex,
      but the latter one possesses a much higher binding energy with the substrate. 

PMID- 19105742
TI  - Mass spectrometry based targeted protein quantification: methods and
      applications.
AB  - The recent advance in technology for mass spectrometry-based targeted protein
      quantification has opened new avenues for a broad range of proteomic applications
      in clinical research. The major breakthroughs are highlighted by the capability
      of using a "universal" approach to perform quantitative assays for a wide
      spectrum of proteins with minimum restrictions and the ease of assembling
      multiplex detections in a single measurement. The quantitative approach relies on
      the use of synthetic stable isotope labeled peptides or proteins, which precisely
      mimic their endogenous counterparts and act as internal standards to quantify the
      corresponding candidate proteins. This report reviews recently developed platform
      technologies for emerging applications of clinical proteomics and biomarker
      development.

PMID- 19105747
TI  - First total synthesis of a polyunsaturated chromone metabolite isolated from the
      brown algae Zonaria tournefortii.
AB  - Starting from the ethyl ester of eicosapentaenoic acid, the first total synthesis
      of the marine natural product all-(Z)-5,7-dihydroxy-2-(4Z,7Z,10Z,13Z,16Z
      nonadecapentaenyl)chromone has been achieved in six steps and in 14% overall
      yield.

PMID- 19105748
TI  - Fluorescent labeling of biomolecules with organic probes.

PMID- 19105749
TI  - The carbon dioxide-water interface at conditions of gas hydrate formation.
AB  - The structure of the carbon dioxide-water interface was analyzed by X-ray
      diffraction and reflectivity at temperature and pressure conditions which allow
      the formation of gas hydrate. The water-gaseous CO2 and the water-liquid CO2
      interface were examined. The two interfaces show a very different behavior with
      respect to the formation of gas hydrate. While the liquid-gas interface exhibits
      the formation of thin liquid CO2 layers on the water surface, the formation of
      small clusters of gas hydrate was observed at the liquid-liquid interface. The
      data obtained from both interfaces points to a gas hydrate formation process
      which may be explained by the so-called local structuring hypothesis.

PMID- 19105750
TI  - Biofuel cell controlled by enzyme logic systems.
AB  - An enzyme-based biofuel cell with a pH-switchable oxygen electrode, controlled by
      enzyme logic operations processing in situ biochemical input signals, has been
      developed. Two Boolean logic gates (AND/OR) were assembled from enzyme systems to
      process biochemical signals and to convert them logically into pH-changes of the
      solution. The cathode used in the biofuel cell was modified with a polymer-brush
      functionalized with Os-complex redox species operating as relay units to mediate
      electron transport between the conductive support and soluble laccase
      biocatalyzing oxygen reduction. The electrochemical activity of the modified
      electrode was switchable by alteration of the solution pH value. The electrode
      was electrochemically mute at pH > 5.5, and it was activated for the
      bioelectrocatalytic oxygen reduction at pH < 4.5. The sharp transition between
      the inactive and active states was used to control the electrode activity by
      external enzymatic systems operating as logic switches in the system. The enzyme
      logic systems were decreasing the pH value upon appropriate combinations of the
      biochemical signals corresponding to the AND/OR Boolean logic. Then the pH
      switchable electrode was activated for the oxygen reduction, and the entire
      biofuel cell was switched ON. The biofuel cell was also switched OFF by another
      biochemical signal which resets the pH value to the original neutral value. The
      present biofuel cell is the first prototype of a future implantable biofuel cell
      controlled by complex biochemical reactions to deliver power on-demand responding
      in a logical way to the physiological needs.

PMID- 19105751
TI  - Mixed-metal assemblies involving ferrocene-naphthyridine hybrids.
AB  - Covalent attachment of one and two NP moieties to a ferrocenyl unit provides
      organometallic ligands 1,8-naphthyrid-2-yl-ferrocene (FcNP) and 1,1'-bis(1,8
      naphthyrid-2-yl)ferrocene (FcNP(2)). Coordination of FcNP to transition metal
      ions Fe(II), Cu(II), Zn(II), and Cd(II) provides [FeCl(2)(kappaN(8)-FcNP)(2)]
      (1), [Cu(kappaN(8)-FcNP)(2)(NO(3))(2)] (2), [Zn(kappaN(8)-FcNP)(4)][OTf](2) (3),
      and [Cd(kappaN(8)-FcNP)(2)(kappa(2)N(1),N(8)-FcNP)(2)][BF(4)](2) (4),
      respectively. Dirhodium(II) compound [Rh(2)(mu-FcNP)(2)(mu
      O(2)CCH(3))(2)(H(2)O)][OTf](2) (5) is isolated when acetonitrile-solvated
      [Rh(2)(mu-O(2)CCH(3))(2)](2+) is employed as a precursor. Diverse bonding modes
      of the NP unit, including monodentate, bidentate chelating, or binuclear
      bridging, are revealed in these FcNP clusters. Metallamacrocycles
      [M(2)(FcNP(2))(2)][X](2) (M = Cu, X = ClO(4) (6); M = Ag, X = OTf (7)),
      [PdCl(2)(FcNP(2))] (8), and [ZnCl(2)(FcNP(2))](4) (10) are obtained by the
      reaction of CuClO(4), AgOTf, Pd(C(6)H(5)CN)(2)Cl(2), and ZnCl(2) with FcNP(2) in
      1:1 ratios. Treatment of Cu(I) and FcNP(2) in a 2:1 ratio provides
      [Cu(2)(FcNP(2))][ClO(4)](2) (9). Molecular structures of compounds 1-10 have been
      determined by X-ray diffraction studies. Interconversion between 1:1 dimer 6 and
      2:1 dimer 9 occurs by the addition of a requisite amount of Cu(I) or FcNP(2). ESI
      MS experiments reveal that the predominant species is the 1:1 complex
      {Cu(FcNP(2))}(1+) in solution for both 6 and 9. Synthesis, structures, mass
      spectroscopy, and electrochemistry of the transition metal compounds of FcNP and
      FcNP(2) are discussed.

PMID- 19105752
TI  - Tuning the oxidation level, the spin state, and the degree of electron
      delocalization in homo- and heteroleptic bis(alpha-diimine)iron complexes.
AB  - The four-coordinate heteroleptic complex [Fe(III)((F)pda(2-))((F)dad*-)] (1) and
      its homoleptic analogue [Fe(II)((F)dad*-)2] (2), where (F)pda(2-) is the closed
      shell ligand N,N'-bis(pentafluorophenyl)-o-phenylenediamide(2-) and (F)dad*- is
      the singly reduced N,N'-bis(pentafluorophenyl)-2,3-dimethyl-1,4-diazabutadiene pi
      radical anion, have been synthesized. X-ray crystallographic studies reveal a
      twisted tetrahedral geometry of the FeN4 coordination polyhedron in both 1 and 2.
      The electronic structures of 1 and 2 were probed by magnetic susceptibility
      measurements, 57Fe Mossbauer and electronic spectroscopy, and density functional
      theory (DFT) calculations. In spite of their similar geometries and a common
      triplet ground state (S(t) = 1), the electronic structures of 1, 2, and the
      previously reported homoleptic analogue [Fe(III)((F)pda(2-))((F)pda*-)] (3),
      where (F)pda*- is a one-electron-oxidized form of (F)pda(2-), differ. The
      electronic structure of 2 consists of two (F)dad*- radicals coupled
      antiferromagnetically to a high-spin Fe(II) center, whereas in 3, only one
      (F)pda*- radical is coupled antiferromagnetically to an intermediate-spin Fe(III)
      ion. This ligand mixed-valent species exhibits class-III behavior. Heteroleptic 1
      contains a single (F)dad*- radical coupled antiferromagnetically to an
      intermediate-spin Fe(III) center but behaves as a class-II ligand mixed-valent
      species. The observed diversity in the electronic structures of 1-3 is ascribed
      to the difference in the redox potentials of the ligands. Analysis of reduced
      orbital charges and spin densities obtained from DFT calculations also suggests
      that the electronic structures of 1-3 are best described as either a high-spin
      Fe(II) ion coordinated to two radical monoanions (2) or as an intermediate-spin
      Fe(III) ion coordinated to one radical monoanion and one closed-shell dianion (1,
      3).

PMID- 19105753
TI  - Design and practices for use of automated drilling and sample handling in MARTE
      while minimizing terrestrial and cross contamination.
AB  - Mars Astrobiology Research and Technology Experiment (MARTE) investigators used
      an automated drill and sample processing hardware to detect and categorize life
      forms found in subsurface rock at Rio Tinto, Spain. For the science to be
      successful, it was necessary for the biomass from other sources--whether from
      previously processed samples (cross contamination) or the terrestrial environment
      (forward contamination)-to be insignificant. The hardware and practices used in
      MARTE were designed around this problem. Here, we describe some of the design
      issues that were faced and classify them into problems that are unique to
      terrestrial tests versus problems that would also exist for a system that was
      flown to Mars. Assessment of the biomass at various stages in the sample handling
      process revealed mixed results; the instrument design seemed to minimize cross
      contamination, but contamination from the surrounding environment sometimes made
      its way onto the surface of samples. Techniques used during the MARTE Rio Tinto
      project, such as facing the sample, appear to remove this environmental
      contamination without introducing significant cross contamination from previous
      samples.

PMID- 19105754
TI  - Science results from a Mars drilling simulation (Rio Tinto, Spain) and ground
      truth for remote science observations.
AB  - Science results from a field-simulated lander payload and post-mission laboratory
      investigations provided "ground truth" to interpret remote science observations
      made as part of the 2005 Mars Astrobiology Research and Technology Experiment
      (MARTE) drilling mission simulation. The experiment was successful in detecting
      evidence for life, habitability, and preservation potential of organics in a
      relevant astrobiological analogue of Mars. SCIENCE RESULTS: Borehole 7 was
      drilled near the Rio Tinto headwaters at Pena de Hierro (Spain) in the upper
      oxidized remnant of an acid rock drainage system. Analysis of 29 cores (215 cm of
      core was recovered from 606 cm penetrated depth) revealed a matrix of goethite-
      (42-94%) and hematite-rich (47-87%) rocks with pockets of phyllosilicates (47
      74%) and fine- to coarse-grained loose material. Post-mission X-ray diffraction
      (XRD) analysis confirmed the range of hematite:goethite mixtures that were
      visually recognizable (approximately 1:1, approximately 1:2, and approximately
      1:3 mixtures displayed a yellowish-red color whereas 3:1 mixtures displayed a
      dark reddish-brown color). Organic carbon was poorly preserved in
      hematite/goethite-rich materials (C(org) <0.05 wt %) beneath the biologically
      active organic-rich soil horizon (C(org) approximately 3-11 wt %) in contrast to
      the phyllosilicate-rich zones (C(org) approximately 0.23 wt %). GROUND TRUTH VS.
      REMOTE SCIENCE ANALYSIS: Laboratory-based analytical results were compared to the
      analyses obtained by a Remote Science Team (RST) using a blind protocol. Ferric
      iron phases, lithostratigraphy, and inferred geologic history were correctly
      identified by the RST with the exception of phyllosilicate-rich materials that
      were misinterpreted as weathered igneous rock. Adenosine 5'-triphosphate (ATP)
      luminometry, a tool available to the RST, revealed ATP amounts above background
      noise, i.e., 278-876 Relative Luminosity Units (RLUs) in only 6 cores, whereas
      organic carbon was detected in all cores. Our manned vs. remote observations
      based on automated acquisitions during the project provide insights for the
      preparation of future astrobiology-driven Mars missions.

PMID- 19105755
TI  - SOLID2: an antibody array-based life-detector instrument in a Mars Drilling
      Simulation Experiment (MARTE).
AB  - A field prototype of an antibody array-based life-detector instrument, Signs Of
      LIfe Detector (SOLID2), has been tested in a Mars drilling mission simulation
      called MARTE (Mars Astrobiology Research and Technology Experiment). As one of
      the analytical instruments on the MARTE robotic drilling rig, SOLID2 performed
      automatic sample processing and analysis of ground core samples (0.5 g) with
      protein microarrays that contained 157 different antibodies. Core samples from
      different depths (down to 5.5 m) were analyzed, and positive reactions were
      obtained in antibodies raised against the Gram-negative bacterium Leptospirillum
      ferrooxidans, a species of the genus Acidithiobacillus (both common
      microorganisms in the Rio Tinto area), and extracts from biofilms and other
      natural samples from the Rio Tinto area. These positive reactions were absent
      when the samples were previously subjected to a high-temperature treatment, which
      indicates the biological origin and structural dependency of the antibody-antigen
      reactions. We conclude that an antibody array-based life-detector instrument like
      SOLID2 can detect complex biological material, and it should be considered as a
      potential analytical instrument for future planetary missions that search for
      life.

PMID- 19105756
TI  - The MARTE VNIR imaging spectrometer experiment: design and analysis.
AB  - We report on the design, operation, and data analysis methods employed on the
      VNIR imaging spectrometer instrument that was part of the Mars Astrobiology
      Research and Technology Experiment (MARTE). The imaging spectrometer is a
      hyperspectral scanning pushbroom device sensitive to VNIR wavelengths from 400
      1000 nm. During the MARTE project, the spectrometer was deployed to the Rio Tinto
      region of Spain. We analyzed subsets of three cores from Rio Tinto using a new
      band modeling technique. We found most of the MARTE drill cores to contain
      predominantly goethite, though spatially coherent areas of hematite were
      identified in Core 23. We also distinguished non Fe-bearing minerals that were
      subsequently analyzed by X-ray diffraction (XRD) and found to be primarily
      muscovite. We present drill core maps that include spectra of goethite, hematite,
      and non Fe-bearing minerals.

PMID- 19105757
TI  - The subsurface geology of Rio Tinto: material examined during a simulated Mars
      drilling mission for the Mars Astrobiology Research and Technology Experiment
      (MARTE).
AB  - The 2005 Mars Astrobiology Research and Technology Experiment (MARTE) project
      conducted a simulated 1-month Mars drilling mission in the Rio Tinto district,
      Spain. Dry robotic drilling, core sampling, and biological and geological
      analytical technologies were collectively tested for the first time for potential
      use on Mars. Drilling and subsurface sampling and analytical technologies are
      being explored for Mars because the subsurface is the most likely place to find
      life on Mars. The objectives of this work are to describe drilling, sampling, and
      analytical procedures; present the geological analysis of core and borehole
      material; and examine lessons learned from the drilling simulation. Drilling
      occurred at an undisclosed location, causing the science team to rely only on
      mission data for geological and biological interpretations. Core and borehole
      imaging was used for micromorphological analysis of rock, targeting rock for
      biological analysis, and making decisions regarding the next day's drilling
      operations. Drilling reached 606 cm depth into poorly consolidated gossan that
      allowed only 35% of core recovery and contributed to borehole wall failure during
      drilling. Core material containing any indication of biology was sampled and
      analyzed in more detail for its confirmation. Despite the poorly consolidated
      nature of the subsurface gossan, dry drilling was able to retrieve useful core
      material for geological and biological analysis. Lessons learned from this
      drilling simulation can guide the development of dry drilling and subsurface
      geological and biological analytical technologies for future Mars drilling
      missions.

PMID- 19105758
TI  - Underground habitats in the Rio Tinto basin: a model for subsurface life habitats
      on Mars.
AB  - A search for evidence of cryptic life in the subsurface region of a fractured
      Paleozoic volcanosedimentary deposit near the source waters of the Rio Tinto
      River (Iberian pyrite belt, southwest Spain) was carried out by Mars Astrobiology
      Research and Technology Experiment (MARTE) project investigators in 2003 and
      2004. This conventional deep-drilling experiment is referred to as the MARTE
      ground truth drilling project. Boreholes were drilled at three sites, and samples
      from extracted cores were analyzed with light microscopy, scanning electron
      microscopy-energy dispersive spectroscopy (SEM-EDS), X-ray diffraction (XRD), and
      Fourier transform infrared spectroscopy. Core leachates were analyzed with ion
      chromatography, and borehole fluids were analyzed with ion and gas
      chromatography. Key variables of the groundwater system (e.g., pO(2), pH, and
      salinity) exhibit huge ranges probably due to surficial oxygenation of overall
      reducing waters, physical mixing of waters, and biologically mediated water-rock
      interactions. Mineral distribution is mainly driven by the pH of subsurface
      solutions, which range from highly acidic to neutral. Borehole fluids contain
      dissolved gases such as CO(2), CH(4), and H(2). SEM-EDS analyses of core samples
      revealed evidence of microbes attacking pyrite. The Rio Tinto alteration
      mechanisms may be similar to subsurface weathering of the martian crust and
      provide insights into the possible (bio)geochemical cycles that may have
      accompanied underground habitats in extensive early Mars volcanic regions and
      associated sulfide ores.

PMID- 19105760
TI  - The golden age of cardiomyogenic stem cells: avoiding a fool's fate.

PMID- 19105759
TI  - Visible-near infrared point spectrometry of drill core samples from Rio Tinto,
      Spain: results from the 2005 Mars Astrobiology Research and Technology Experiment
      (MARTE) drilling exercise.
AB  - Sampling of subsurface rock may be required to detect evidence of past biological
      activity on Mars. The Mars Astrobiology Research and Technology Experiment
      (MARTE) utilized the Rio Tinto region, Spain, as a Mars analog site to test dry
      drilling technologies specific to Mars that retrieve subsurface rock for
      biological analysis. This work examines the usefulness of visible-near infrared
      (VNIR) (450-1000 nm) point spectrometry to characterize ferric iron minerals in
      core material retrieved during a simulated Mars drilling mission. VNIR
      spectrometry can indicate the presence of aqueously precipitated ferric iron
      minerals and, thus, determine whether biological analysis of retrieved rock is
      warranted. Core spectra obtained during the mission with T1 (893-897 nm) and T2
      (644-652 nm) features indicate goethite-dominated samples, while relatively lower
      wavelength T1 (832-880 nm) features indicate hematite. Hematite/goethite molar
      ratios varied from 0 to 1.4, and within the 880-898 nm range, T1 features were
      used to estimate hematite/goethite molar ratios. Post-mission X-ray analysis
      detected phyllosilicates, which indicates that examining beyond the VNIR (e.g.,
      shortwave infrared, 1000-2500 nm) will enhance the detection of other minerals
      formed by aqueous processes. Despite the limited spectral range of VNIR point
      spectrometry utilized in the MARTE Mars drilling simulation project, ferric iron
      minerals could be identified in retrieved core material, and their distribution
      served to direct core subsampling for biological analysis.

PMID- 19105762
TI  - The CHARM program: the effects of candesartan for the management of patients with
      chronic heart failure.
AB  - Recent studies have shown candesartan to be an effective therapy for heart
      failure (HF) patients, producing a significant reduction in cardiovascular
      mortality and morbidity. Importantly studies have shown that candesartan is
      effective in HF patients intolerant to angiotensin-converting enzyme inhibitors
      and in patients already receiving angiotensin-converting enzyme inhibitors as
      well as and providing evidence that it may also be effective for HF patients with
      preserved ejection fraction. The primary end point in the latter group failed to
      achieve statistical significance owing to the small number of events. This paper
      will review the data supporting the use of candesartan to treat all HF patients,
      regardless of their ejection fraction.

PMID- 19105763
TI  - Efficacy and safety of prasugrel compared with clopidogrel in patients with acute
      coronary syndromes: results of TRITON-TIMI 38 trials.
AB  - Current guidelines recommend dual antiplatelet therapy using aspirin and
      clopidogrel for non-ST elevation acute coronary syndromes (ACS). Despite the
      established benefits of this approach, many patients continue to have recurrent
      atherothrombotic events. Moreover, it is often difficult to achieve an adequate
      inhibition of platelet aggregation with clopidogrel in clinical practice.
      Prasugrel is an orally administered P2Y12 receptor antagonist that is more
      potent, more rapid in onset and more consistent in its inhibition of platelet
      aggregation than currently approved doses of clopidogrel. The trial to Assess
      Improvement in Therapeutic Outcomes by Optimizing Platelet Inhibition with
      Prasugrel - Thrombolysis in Myocardial Infarction 38 (TRITON-TIMI 38) randomized
      13,608 moderate-to-high-risk patients with ACS (with or without ST-segment
      elevation) undergoing percutaneus coronary intervention to compare prasugrel with
      clopidogrel for a median of follow-up time of 14.5 months. The TRITON-TIMI 38
      trial demonstrated a significant reduction in ischemic events in patients
      randomized to prasugrel compared with those treated with clopidogrel. This
      beneficial effect, however, was associated with a significant increase in major
      bleeding.

PMID- 19105764
TI  - Atheromatous plaque hemorrhage: early detection and its impact on the management
      of patients with carotid artery disease.

PMID- 19105765
TI  - Neuroimaging of ischemic stroke with CT and MRI: advancing towards physiology
      based diagnosis and therapy.
AB  - Acute ischemic stroke is the third leading cause of death and the major cause of
      significant disability in adults in the USA and Europe. The number of patients
      who are actually treated for acute ischemic stroke is disappointingly low,
      despite availability of effective treatments. A major obstacle is the short
      window of time following stroke in which therapies are effective. Modern imaging
      is able to identify the ischemic penumbra, a key concept in stroke physiology.
      Evidence is accumulating that identification of a penumbra enhances patient
      management, resulting in significantly improved outcomes. Moreover, unexpectedly
      large proportions of patients have a substantial ischemic penumbra beyond the
      traditional time window and are suitable for therapy. The widespread availability
      of modern MRI and computed tomography systems presents new opportunities to use
      physiology to guide ischemic stroke therapy in individual patients. This article
      suggests an evidence-based alternative to contemporary acute ischemic stroke
      therapy.

PMID- 19105766
TI  - Myocardial perfusion imaging to assess ischemia using multislice computed
      tomography.
AB  - Multislice computed tomography (MSCT) coronary angiography is an accurate
      noninvasive anatomic imaging technique; but it cannot determine the functional
      relevance of the lesions it detects. However, MSCT perfusion imaging can detect
      the presence of myocardial infarction during rest and assess viability using
      delayed enhancement. With recent developments in MSCT scanner technology, it has
      become possible to image myocardial perfusion and the capability of MSCT to
      determine the presence of ischemia through perfusion imaging during stress is
      currently being investigated. Although only limited data are available,
      noninvasive imaging with MSCT has the potential to assess both coronary anatomy
      and myocardial perfusion in one procedure. This article describes the feasibility
      of myocardial perfusion imaging using MSCT and its potential use in clinical
      practice.

PMID- 19105767
TI  - Detection of noncalcified and mixed plaque by multirow detector computed
      tomography.
AB  - New tomographic cardiovascular imaging tests, such as intravascular
      ultrasonography and coronary computed tomography angiography, can be used to
      assess atherosclerotic plaques for the characterization and early staging of
      coronary artery disease (CAD). Although intravascular ultrasonography provides
      high-resolution images that are capable of revealing early preclinical CAD, it is
      a highly invasive technique used clinically only in conjunction with coronary
      interventions. Multidetector computed tomography angiography, which is
      noninvasive and corresponds well with plaque histology, shows promise as a
      diagnostic method for CAD and can provide general evaluation of noncalcified and
      mixed plaque composition. The current generation of 64-slice computed tomography
      scanners have high accuracy for detection of lesions obstructing more than 50% of
      the lumen, with sensitivity, specificity, and positive and negative predictive
      values all over 90% in patients without known CAD. They may have an important
      role in characterizing high-risk noncalcified and mixed plaques. Review of the
      currently available literature suggests that tissue density measured by
      multidetector computed tomography can be used to accurately characterize coronary
      atherosclerotic plaque composition. With further advances in tomographic
      angiography, the goal will be to detect plaques earlier in the development of CAD
      and to characterize the plaques most likely to generate a clinical event.

PMID- 19105768
TI  - Role of nuclear imaging in cardiac resynchronization therapy.
AB  - Cardiac resynchronization therapy (CRT) has become an integrated treatment option
      for patients with drug-refractory heart failure. Selection of patients for CRT is
      based on moderate-to-severe heart failure (New York Heart Association functional
      class III or IV), depressed left ventricular (LV) systolic function of 35% or
      below and prolonged QRS interval of 120 ms or more. However, 30-40% of selected
      patients do not exhibit improvement in heart failure symptoms or LV systolic
      performance. Efforts have been made to improve patient selection criteria and
      several studies using echocardiography have demonstrated the significance of LV
      dyssynchrony for prediction of CRT response as an additional selection criteria.
      In addition, (location and extent of) viability and scar tissue are important for
      outcome following CRT. Nuclear imaging with ECG-gated myocardial perfusion single
      photon emission computed tomography (GMPS) permits assessment of viability, scar
      tissue and LV dyssynchrony from one dataset; the potential value of GMPS in CRT
      patients is discussed in this review. In addition, the use of nuclear imaging
      (and particularly PET) for evaluation of changes in blood flow, metabolism and
      innervation after CRT is addressed.

PMID- 19105769
TI  - Surgery for functional tricuspid regurgitation: current techniques, outcomes and
      emerging concepts.
AB  - Functional tricuspid regurgitation is the most frequent cause of tricuspid
      insufficiency and is often secondary to left-sided valve diseases. The correction
      of left-sided valve diseases without concomitant repair of functional tricuspid
      regurgitation is associated with significant late morbidity and mortality. This
      occurs on account of progressive right ventricular dysfunction and increasing
      need for reoperation. Recent years have seen a surge in surgery for functional
      tricuspid regurgitation. Several techniques are available to correct functional
      tricuspid regurgitation. These include the stitch annuloplasty, such as
      semicircular (classical De Vega repair) or simple lateral annuloplasty (Kay),
      novel techniques such as edge-to-edge or clover technique and suture
      bicuspidization technique, use of flexible and rigid prosthetic rings or 3D
      rings, flexible prosthetic bands, and use of artificial chordae with
      polytetrafluoroethylene sutures for anterior and septal ticuspid leaflet
      pathology. Whereas the short-term outcomes of these techniques are satisfactory,
      the majority are limited in the mid- and long term by unacceptably high rates of
      residual and/or recurrent regurgitation. A better understanding of the mechanisms
      of functional tricuspid regurgitation will help explain the failure of current
      techniques and be a help to modify existing surgical techniques or develop new
      techniques.

PMID- 19105770
TI  - Pharmacologic therapy for coronary atherosclerosis in patients with Type 2
      diabetes mellitus.
AB  - Accelerated progression of coronary atherosclerosis underlies the heightened
      cardiovascular risk observed in diabetic patients. As the worldwide prevalence of
      diabetes escalates in association with the incidence of abdominal obesity, the
      global burden of cardiovascular disease will continue to rise. Therapeutic
      strategies that have had the greatest cardiovascular benefit in diabetes have
      focused on lowering LDL-cholesterol and blood pressure, rather than glucose
      lowering specifically. More recently, arterial wall imaging has helped
      characterize the natural history of coronary atherosclerosis in diabetes, the
      impact of associated risk factors and the influence of medical therapies.

PMID- 19105773
TI  - Comparison between slow freezing and vitrification for human embryos.

PMID- 19105774
TI  - Study on retinal prostheses increases patient enrollment.

PMID- 19105775
TI  - e100 NeuroRobotic system.
AB  - Therapy incorporating the repeated practice of motor tasks has been found to
      enhance motor function after stroke. This type of therapy may be facilitated by
      robotic devices and several such devices are being developed for use in
      rehabilitation. The Myomo e100 NeuroRobotic system is a novel device developed to
      provide assistance during elbow movements in stroke survivors. The device uses
      surface electromyographic signals to control a powered elbow orthosis. Data from
      a pilot study reveals that the device can be used successfully by stroke
      survivors and suggests that it may be effective in helping to restore motor
      control after stroke. Further studies are needed to confirm these preliminary
      results.

PMID- 19105776
TI  - Early results with the cementless Variall hip system.
AB  - This study presents the early results of the Variall cementless hip system, a
      further development of the reliable Alloclassic Zweymuller system. In a
      prospective randomized study, 319 patients (333 hips) underwent the Variall
      cementless hip system with four different bearings and were scored using the
      Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Score and
      the Short Form-36 health survey form, with a follow-up period of 3 years. The
      patients were grouped according to age, with those in the age range 23-75 years
      as group one (n = 285) and those over 75 years of age as group two (n = 48). For
      both the Short Form-36 and WOMAC scoring, worse function was found in group two
      (i.e., patients >75 years). In this group, the function scores were worse in
      patients who received a conventional polyethylene bearing. The clinical and
      radiological results after 5 or more years will lead to a clearer prediction.

PMID- 19105777
TI  - Xoft Axxent electronic brachytherapy.
AB  - Balloon-based brachytherapy was developed to render accelerated partial-breast
      irradiation more accessible to breast cancer patients. Xoft Axxent electronic
      brachytherapy (eBX) is a novel method of accelerated partial-breast irradiation
      that utilizes an electronic source to produce x-rays. eBX does not require a high
      dose rate afterloader unit or a shielded vault and, thus, may appeal to a larger
      number of patients undergoing the accelerated partial-breast irradiation
      procedure. eBX is associated with a lower radiation dose to normal tissues and
      larger 'hot spots' than treatment with the MammoSite device. Additional
      applications are also being developed for eBX, including endometrial cancer
      treatment.

PMID- 19105778
TI  - A review of current devices and a look at new technology: drug-eluting stents.
AB  - Drug-eluting stents (DES) have become the standard of care for the treatment of
      coronary artery disease. However, late stent thrombosis has emerged as a major
      concern, especially in 'off-label' use. Pathologic studies of patients dying from
      late DES thrombosis demonstrate delayed arterial healing, characterized by
      persistent fibrin deposition and poor endothelialization as the primary
      substrate. Therefore, next-generation DES are being developed to increase the
      safety and biocompatibility by optimizing the three major components of DES: the
      stent platform, the polymer and the drug. Stents with thinner struts are
      endothelialized rapidly and cause less vessel-wall injury. Non-erodable polymers
      applied thinly and without defect or cracking cause less inflammation and will
      result in better long-term safety. Furthermore, use of biodegradable polymers,
      which fully degrade and leave a bare metal stent, will result in less
      inflammation. The choice of drug, dose and release kinetics should also be
      optimized. In addition to the improvement of DES components, new approaches, such
      as polymer-free drug delivery, prohealing approach and fully biodegradable
      stents, are emerging. Importantly, these technologies focus not only on efficacy
      but also on safety. The next-generation DES will probably be safer, with goals of
      improving endothelialization and more rapid arterial healing compared with first-
      and second-generation DES.

PMID- 19105779
TI  - The implantable cardioverter defibrillator: its history, current psychological
      impact and future.
AB  - The innovation of the implantable cardioverter defibrillator (ICD) represents a
      modern medical achievement with substantial life-saving benefits for patients at
      risk for potentially life-threatening arrhythmias. Over a decade of research
      resulted in the first ICD implantation in 1980, dramatically changing the face of
      cardiac care. The introduction of the device was met by skepticism and outright
      rejection by some, yet large-scale clinical trials clearly demonstrated the
      mortality benefit of the ICD. Today, specific challenges for this technology have
      emerged, including barriers to individual and social acceptance of the ICD as a
      viable form of technology, as well as psychosocial adjustment difficulties and
      fears in patients. To address these challenges, scientific research, improved
      communication regarding devices and psychosocial interventions have been
      developed and extended to this patient population. As such, it is hypothesized
      that the future will hold expanding indications for ICD implantation, while
      further meeting patients' medical and psychosocial adjustment needs. The purposes
      of this paper are to review the history of ICD innovation, describe past and
      present research on psychosocial adjustment to the ICD, and corresponding
      psychosocial interventions, analyze individual and social acceptance and
      utilization of device technology, and forecast future applications and
      developments of the ICD.

PMID- 19105780
TI  - Surface coatings for ventricular assist devices.
AB  - This article focuses on the surface engineering of ventricular assist devices
      (VADs) for the treatment of heart failure patients, which involves the
      modification of surfaces contacting blood in order to improve the blood
      compatibility (hemocompatibility) of the VADs. Following an introduction to the
      categorization and the complications of VADs, this article pays attention on the
      hemocompatibility, applications and limitations of six types of surface coatings
      for VADs: titanium nitride coatings, diamond-like carbon coatings, 2
      methacryloyloxyethyl phosphorylcholine polymer coatings, heparin coatings,
      textured surfaces and endothelial cell linings. In particular, diamond-like
      coatings and heparin coatings are the most commonly used for VADs owing to their
      excellent hemocompatibility, durability and technical maturity. For high
      performance and a long lifetime of VADs, surface modification with coatings to
      ensure hemocompatibility is as important as the mechanical design of the device.

PMID- 19105781
TI  - Scaffolds for tendon and ligament repair: review of the efficacy of commercial
      products.
AB  - Driven by market demand, many biological and synthetic scaffolds have been
      developed during the last 15 years. Both positive and negative results have been
      reported in clinical applications for tendon and ligament repair. To obtain data
      for this review, multiple electronic databases were used (e.g., Pubmed and
      ScienceDirect), as well as the US FDA website and the reference lists from
      clinical trials, review articles and company reports, in order to identify
      studies relating to the use of these commercial scaffolds for tendon and ligament
      repair. The commercial names of each scaffold and the keywords 'tendon' and
      'ligament' were used as the search terms. Initially, 378 articles were
      identified. Of these, 47 were clinical studies and the others were reviews,
      editorials, commentaries, animal studies or related to applications other than
      tendons and ligaments. The outcomes were reviewed in 47 reports (six on Restore,
      eight on Graftjacket, four on Zimmer, one on TissueMend, five on Gore-Tex, six on
      Lars, 18 on Leeds-Keio and one study used both Restore and Graftjacket). The
      advantages, disadvantages and future perspectives regarding the use of commercial
      scaffolds for tendon and ligament treatment are discussed. Both biological and
      synthetic scaffolds can cause adverse events such as noninfectious effusion and
      synovitis, which result in the failure of surgery. Future improvements should
      focus on both mechanical properties and biocompatibility. Nanoscaffold
      manufactured using electrospinning technology may provide great improvement in
      future practice.

PMID- 19105782
TI  - Techniques for managing anatomic variations in primary total knee arthroplasty.
AB  - Primary total knee arthroplasties have high success rates, but certain patient
      anatomic or other variations may adversely affect the performance or the clinical
      outcomes of these procedures. Various technologies and techniques have been
      developed in attempts to overcome these challenges. However, there is controversy
      concerning whether these innovations are beneficial. This article assessed the
      scientific evidence regarding the use of these technologies to address various
      anatomic variations by examining the complete body of literature. The anatomic
      variations that were examined included extra-articular deformities, bone
      deficiencies, ligamentous instability, post-patellectomy knees, patella baja,
      variations in bone size and high-flexion knees. Recommendations for each
      circumstance were presented based upon the available scientific evidence.

PMID- 19105783
TI  - Devices for laparoendoscopic single-site surgery in urology.
AB  - The quest to make minimally invasive techniques even more 'minimal' has generated
      a drive within the surgical community to explore novel ways of achieving this.
      This has led to surgeons attempting to either decrease the number of trocars
      placed through the abdominal wall or eliminate them completely. This led to the
      evolution of several approaches, including natural orifice translumenal
      endoscopic surgery (NOTES), single incision laparoscopic surgery (SILS), single
      port access surgery and one port umbilical surgery (OPUS) or E-NOTES. The most
      recent consensus on nomenclature involves the term laparoendoscopic single-site
      surgery (LESS). The transition from multiple port access surgery to single port
      access surgery represents a paradigm shift in reconstructive and extirpative
      surgery and is a testament to the recent advances in surgical technology.
      Successful LESS involves the use of articulating or bent instrumentation via a
      single large-caliber trocar or small, adjacent trocars. Advances in technology
      have led to the development of new laparoscopic access ports (R-Port and
      Quadriport by Advanced Surgical Concepts, Wicklow, Ireland; and Uni-X Single
      Port, PNavel Systems, Cleveland, OH, USA) capable of permitting several
      instruments to be inserted through multiple channels incorporated in, and as part
      of, a larger single port. The development of articulating and bent
      instrumentation permits triangulation intracorporeally despite the close
      proximity of several instruments via a single port. Currently, commercially
      available instruments can be broadly divided into articulating laparoscopic
      graspers and shears (Real Hand, Novare Surgical Systems, Cupertino, CA, USA; and
      Autonomy Laparo-angle, Cambridge Endo, Framingham, MA, USA), endoshears
      (Cambridge Endo), and laparoscopic needle drivers (Cambridge Endo). Despite the
      preliminary optimistic results in the outcomes of LESS, an experienced
      laparoscopic skill set is essential for the safe and effective completion of
      surgery.

PMID- 19105785
TI  - Bioconjugation of biotin to the interfaces of polymeric micelles via in situ
      click chemistry.
AB  - Azido-containing amphiphilic triblock copolymer poly(ethylene glycol)-b
      poly(azidoethyl methacrylate)-b-poly(methyl methacrylate) (PEG-b-PAzEMA-b-PMMA)
      was prepared by postpolymerization functionalization of poly(ethylene glycol)-b
      poly(hydroxyethyl methacrylate)-b-poly(methyl methacrylate) (PEG-b-PHEMA-b-PMMA).
      In aqueous media, PEG-b-PAzEMA-b-PMMA self-assembled into spherical micelles with
      the azide groups at the hydrophobic/hydrophilic interface due to the molecular
      architecture. Biotin was conjugated to the micelles by in situ click chemistry
      between azide groups and alkynated biotin, resulting in the formation of a
      functional interface between the hydrophilic shell and the hydrophobic core. The
      bioavailability of biotin to avidin was demonstrated by an avidin/4'
      hydroxyazobenzene-2-carboxylic acid (avidin/HABA) assay, transmission electron
      microscopy, and dynamic light scattering investigations.

PMID- 19105786
TI  - Biomimetic nerve scaffolds with aligned intraluminal microchannels: a "sweet"
      approach to tissue engineering.
AB  - In this paper, we outline a method for the fabrication of biomimetic hollow fiber
      and hollow fiber bundles with high aspect ratios. The manufacturing process
      utilizes a melt spinning technique with caramelized sucrose as a core template.
      Encapsulation of the sucrose with a thin layer of degradable polymer and
      selective dissolution of the sucrose core produced tubes and tube aggregates with
      geometries similar to biologic analogs. The manufacturing process requires no
      specialized equipment and minimal quantities of organic solvent/polymer. These
      scaffolds were shown to induce nerve and glial cell alignment in vitro and may be
      further customized to integrate with other tissue or cell culture systems.

PMID- 19105787
TI  - A novel approach to determine the critical coagulation concentration of a
      colloidal dispersion with plate-like particles.
AB  - The critical coagulation concentration (ccc) of counterions is commonly described
      by the classical Derjaguin-Landau-Verwey-Overbeek (DLVO) theory on the basis of a
      static force balance. It can, however, also be estimated from a kinetic point of
      view by studying the process of colloidal coagulation, or from a dynamic point of
      view by considering colloidal transport in nonequilibrium systems where other
      processes such as diffusion and the influence of gravity come into play. In
      particular, in a test tube where colloidal expansion takes place, the ccc can be
      interpreted as the electrolyte concentration below which expansion of colloids
      would always lead to full access to the entire volume of the test tube and above
      which a sharp boundary is established between a colloidal gel and pure water. On
      the basis of this perception and the dynamic force balance model that we
      developed to describe colloidal expansion in a test tube, accounting for the
      effects of particle diffusion and gravity in contrast to the DLVO theory, we
      propose an alternative way to assess the ccc of counterions. We also derive an
      approximate expression for the case of homointeraction at constant charge for
      montmorillonite. The estimated ccc values agree quite well with those observed
      experimentally for both Na(+) and Ca(2+) counterions for montmorillonite
      dispersions, at pH approximately 6.5. This is in contrast to the DLVO theory,
      which overpredicts the ccc by about 2 orders of magnitude. In addition, the
      detailed analyses suggest that the ccc of counterions decreases with increasing
      surface area and with the thickness of the particles. For montmorillonite, the
      ccc is nearly independent of the surface charge density of the particles for the
      range of typical charge densities.

PMID- 19105788
TI  - A dynamic force balance model for colloidal expansion and its DLVO-based
      application.
AB  - A force balance model that describes the dynamic expansion of colloidal bentonite
      gels/sols is presented. The colloidal particles are assumed to consist of one or
      several thin sheets with the other dimensions much larger than their thickness.
      The forces considered include van der Waals force, diffuse double layer force,
      thermal force giving rise to Brownian motion, gravity, as well as friction force.
      The model results in an expression resembling the instationary diffusion equation
      but with an immensely variable diffusivity. This diffusivity is strongly
      influenced by the concentration of counterions as well as by the particle
      concentration in the colloid gel/sol. The properties of the model are explored
      and discussed, exemplified by the upward expansion of an originally highly
      compacted bentonite tablet in a test tube. Examples are presented for a number of
      cases with ionic concentrations varying between very dilute waters up to several
      molar of counterions. The volume fraction of particles ranges from 40% to very
      dilute sols.

PMID- 19105789
TI  - Facile synthesis of tin oxide nanoflowers: a potential high-capacity lithium-ion
      storage material.
AB  - A facile and reproducible approach was reported to synthesize nanoparticle
      attached SnO nanoflowers via decomposition of an intermediate product Sn6O4(OH)4.
      Sn6O4(OH)4 formed after introducing water into the traditional nonaqueous
      reaction, and then decomposed to SnO nanoflowers with the help of free metal
      cations, such as Sn2+, Fe2+, and Mn2+. This free cation-induced formation process
      was found independent of the nature of the surface ligand. It was demonstrated
      further that the as-prepared SnO nanoflowers could be utilized as good anode
      materials for lithium ion rechargeable batteries with a high capacity of around
      800 mA h g(-1), close to the theoretical value (875 mA h g(-1)).

PMID- 19105790
TI  - Molecular orientation in octanedithiol and hexadecanethiol monolayers on GaAs and
      Au measured by infrared spectroscopic ellipsometry.
AB  - Infrared spectroscopic ellipsometry was used for determination of molecular
      orientation and for lateral homogeneity studies of organic monolayers on GaAs and
      Au, the organic layer being either octanedithiol or hexadecanethiol (HDT). The
      laterally resolved measurements were performed with the infrared mapping
      ellipsometer at the synchrotron storage ring BESSY II. The molecular orientation
      within the monolayers was determined by optical model simulations of the measured
      ellipsometric spectra. Different tilt angles were obtained for the monolayers of
      HDT and octanedithiol on GaAs: 19 degrees and >30 degrees , respectively. The
      tilt angle of the methylene chains for HDT on Au substrate (22 degrees ) is
      similar to the 19 degrees tilt which was obtained for the HDT monolayers on GaAs,
      thus suggesting similar molecular ordering of the thiolates on both substrates.

PMID- 19105791
TI  - Arginine, citrulline and nitric oxide metabolism in sepsis.
AB  - Arginine has vasodilatory effects, via its conversion by NO synthase into NO, and
      immunomodulatory actions which play important roles in sepsis. Protein breakdown
      affects arginine availability and the release of asymmetric dimethylarginine, an
      inhibitor of NO synthase, may therefore affect NO synthesis in patients with
      sepsis. The objective of the present study was to investigate whole-body in vivo
      arginine and citrulline metabolism and NO synthesis rates, and their relationship
      to protein breakdown in patients with sepsis or septic shock and in healthy
      volunteers. Endogenous leucine flux, an index of whole-body protein breakdown
      rate, was measured in 13 critically ill patients with sepsis or septic shock and
      seven healthy controls using an intravenous infusion of [1-13C]leucine. Arginine
      flux, citrulline flux and the rate of conversion of arginine into citrulline (an
      index of NO synthesis) were measured with intravenous infusions of
      [15N2]guanidino-arginine and [5,5-2H2]citrulline. Plasma concentrations of
      nitrite plus nitrate, arginine, citrulline and asymmetric dimethylarginine were
      measured. Compared with controls, patients had a higher leucine flux and higher
      NO metabolites, but arginine flux, plasma asymmetric dimethylarginine
      concentration and the rate of NO synthesis were not different. Citrulline flux
      and plasma arginine and citrulline were lower in patients than in controls.
      Arginine production was positively correlated with the protein breakdown rate.
      Whole-body arginine production and NO synthesis were similar in patients with
      sepsis and septic shock and healthy controls. Despite increased proteolysis in
      sepsis, there is a decreased arginine plasma concentration, suggesting inadequate
      de novo synthesis secondary to decreased citrulline production.

PMID- 19105792
TI  - Peroxiredoxin 4 knockout results in elevated spermatogenic cell death via
      oxidative stress.
AB  - Prx (peroxiredoxin) is a multifunctional redox protein with thioredoxin-dependent
      peroxidase activity. Prx4 is present as a secretory protein in most tissues,
      whereas in sexually mature testes it is anchored in the ER (endoplasmic
      reticulum) membrane of spermatogenic cells via an uncleaved N-terminal
      hydrophobic peptide. We generated a Prx4 knockout mouse to investigate the
      function of Prx4 in vivo. Prx4(-/y) mice lacking Prx4 expression in all cells
      were obtained by mating Prx4(flox/+) female mice with Cre-transgenic male mice
      that ubiquitously expressed Cre recombinase. The resulting Prx4(-/y) male mice
      were fertile, and most organs were nearly normal in size, except for testicular
      atrophy. The number of deoxynucleotidyl transferase-mediated dUTP nick end
      labelling-positive spermatogenic cells was higher in Prx4(-/y) mice than in
      Prx4(+/y) mice and increased remarkably in response to warming the lower abdomen
      at 43 degrees C for 15 min. Cells reactive to antibodies against 4-hydroxynonenal
      and 8-hydroxyguanine were high in the Prx4(-/y) mice and concomitant with
      elevated oxidation of lipid and protein thiols. The cauda epididymis of Prx4(-/y)
      mice contained round spermatocytes, which were not found in Prx4(+/y) mice, and
      displayed oligozoospermia. However, mature spermatozoa from the epididymis of
      Prx4(-/y) mice exhibited normal fertilization In vitro. Taken together, these
      results indicate that spermatogenic cells lacking Prx4 are more susceptible to
      cell death via oxidative damage than their wild-type counterparts. Our results
      suggest that the presence of Prx4, most likely the membrane-bound form, is
      important for spermatogenesis, but not an absolute requisite.

PMID- 19105793
TI  - Membrane-targeted synergistic activity of docosahexaenoic acid and lysozyme
      against Pseudomonas aeruginosa.
AB  - Antimicrobial polypeptides, including lysozymes, have membrane perturbing
      activity and are well-documented effector molecules of innate immunity. In cystic
      fibrosis, a hereditary disease with frequent lung infection with Pseudomonas
      aeruginosa, the non-esterified fatty acid DA (docosahexaenoic acid), but not OA
      (oleic acid), is decreased, and DA supplementation has been shown to improve the
      clinical condition in these patients. We hypothesized that DA may, either alone
      or in conjunction with lysozyme, exert antibacterial action against Ps.
      aeruginosa. We found that DA and lysozyme synergistically inhibit the metabolic
      activity of Ps. aeruginosa, in contrast with OA. Electron microscopy and
      equilibrium dialysis suggest that DA accumulates in the bacterial membrane in the
      presence of lysozyme. Surface plasmon resonance with live bacteria and
      differential scanning calorimetry studies with bacterial model membranes reveal
      that, initially, DA facilitates lysozyme incorporation into the membrane, which
      in turn allows influx of more DA, leading to bacterial cell death. The present
      study elucidates a molecular basis for the synergistic action of non-esterified
      fatty acids and antimicrobial polypeptides, which may be dysfunctional in cystic
      fibrosis.

PMID- 19105794
TI  - Severe community acquired pneumonia update: mortality, mechanisms and medical
      intervention.

PMID- 19105795
TI  - Demographics, guidelines, and clinical experience in severe community-acquired
      pneumonia.
AB  - Mortality in patients with community-acquired pneumonia (CAP) who require
      intubation or support with inotropes in an intensive care unit setting remains
      extremely high (up to 50%). Systematic use of objective severity-of-illness
      criteria, such as the Pneumonia Severity Index (PSI), British Thoracic Society
      CURB-65 (an acronym meaning Confusion, Urea, Respiratory rate, Blood pressure,
      age >/=65 years), or criteria developed by the Infectious Diseases Society of
      America/American Thoracic Society, to aid site-of-care decisions for pneumonia
      patients is emerging as a step forward in patient management. Experience with the
      Predisposition, Infection, Response, and Organ dysfunction (PIRO) score, which
      incorporates key signs and symptoms of sepsis and important CAP risk factors, may
      represent an improvement in staging severe CAP. In addition, it has been
      suggested that implementing a simple care bundle in the emergency department will
      improve management of CAP, using five evidence-based variables, with immediate
      pulse oxymetry and oxygen assessment as the cornerstone and initial step of
      treatment.

PMID- 19105796
TI  - Tissue factor as an initiator of coagulation and inflammation in the lung.
AB  - Patients with severe infections almost invariably exhibit evidence of activation
      of the coagulation system. The lungs are amongst the most frequently affected
      organs during severe infection and sepsis. The abundant presence of intravascular
      and extravascular fibrin appears to be a specific hallmark of acute lung injury
      after sepsis. Tissue factor (TF) is regarded to be the primary initiator of
      coagulation in severe infection. Effective blockade of the TF pathway, either by
      recombinant TF pathway inhibitor or by anti-TF antibodies in experimental sepsis,
      attenuates lung injury and partially prevents pulmonary dysfunction. In addition,
      inhibition of the activity of TF prevents local activation of coagulation in
      models of pneumonia. The TF pathway can influence inflammatory signaling by
      activation of protease activated receptor-1 and -2. This review presents the most
      recent data on the crosstalk between TF-mediated coagulation and inflammation,
      with a specific emphasis on these processes in the lung.

PMID- 19105797
TI  - Beyond antibiotics in severe community-acquired pneumonia: the role and rationale
      for tissue factor pathway inhibition.
AB  - Despite effective antibiotic therapy, about one-third of patients admitted to an
      intensive care unit (ICU) with severe community-acquired pneumonia (CAP) and
      organ dysfunction die within a month. This high death rate demonstrates the need
      for additional interventions. Both animal models and clinical data suggest that
      pathological expression of tissue factor (TF), with consequent activation of
      coagulation and inflammatory processes, contributes to the morbidity and
      mortality associated with CAP. TF pathway inhibitor (TFPI) is an endogenous
      molecule with both anti-inflammatory and anti-coagulant activity. In severe CAP,
      endogenous TFPI is overwhelmed by increased expression of TF. In this setting
      administration of recombinant TFPI (tifacogin) could restore hemostasis. The
      OPTIMIST phase 3 trial of tifacogin in severe sepsis did not show overall
      mortality benefit from tifacogin. However, retrospective analysis suggested
      improved survival among tifacogin treated patients who had severe CAP. Benefit
      seemed clearest when such patients had not received concurrent heparin and/or
      when they had documented microbial infection. These findings led to a prospective
      study (CAPTIVATE) in which 2,100 patients with severe CAP requiring ICU admission
      were randomized to standard care plus either placebo or one of two dose levels of
      tifacogin. The study excluded concomitant heparin and encouraged documentation of
      infection. Enrolment was completed in July 2008 but data are not yet available.
      The primary outcome measure is 28-day all-cause mortality. In addition to short
      term and long-term survival, the study is collecting data on adverse events
      (particularly when related to bleeding or thrombosis) and the effect of tifacogin
      on disease progression, resource use, and duration of ICU and hospital stay.

PMID- 19105798
TI  - The role of biomarkers in community-acquired pneumonia: predicting mortality and
      response to adjunctive therapy.
AB  - Patients with community-acquired pneumonia (CAP) in the hospital setting exhibit
      markedly abnormal levels of various biomarkers of infection, inflammation and
      coagulation. CAP is a well characterized disease, relatively homogeneous and
      amenable to management according to defined protocols. Hence, this group of
      patients represents an opportunity to investigate further these biomarkers as a
      means of determining disease severity and identifying candidates for new
      therapies. Changes in biomarker levels during the course of disease may enable
      physicians to identify those patients who are most at risk for deterioration and
      progression toward severe CAP and who are in greatest need of early intervention.
      Subgroup analysis of the placebo-controlled OPTIMIST trial of tifacogin in severe
      sepsis revealed a trend toward benefit in patients with procalcitonin levels of 2
      ng/ml or greater and in those with high baseline markers of activated
      coagulation. Biomarker studies are being undertaken as part of the ongoing
      CAPTIVATE study. This study includes patients with severe CAP and will compare
      the efficacy and safety of recombinant tissue factor pathway inhibitor
      (tifacogin) versus placebo. In the future it may also be possible to use genomic
      markers to identify patients at greatest risk for deterioration or complications.

PMID- 19105799
TI  - Dermatological conditions in intensive care: a secondary analysis of the
      Intensive Care National Audit and Research Centre (ICNARC) Case Mix Programme
      database.
AB  - INTRODUCTION: Dermatology is usually thought of as an outpatient specialty with
      low mortality, however some skin conditions require intensive care. These
      conditions are relatively rare and hence are best studied using clinical
      databases or disease registries. We interrogated a large, high-quality clinical
      database from a national audit of adult intensive care units (ICUs), with the aim
      of identifying and characterising patients with dermatological conditions
      requiring admission to ICU. METHODS: Data were extracted for 476,224 admissions
      to 178 ICUs in England, Wales and Northern Ireland participating in the Case Mix
      Programme over the time period December 1995 to September 2006. We identified
      admissions with dermatological conditions from the primary and secondary reasons
      for admission to ICU. RESULTS: A total of 2,245 dermatological admissions were
      identified. Conditions included infectious conditions (e.g. cutaneous cellulitis,
      necrotising fasciitis), dermatological malignancies, and acute skin failure (e.g.
      toxic epidermal necrolysis, Stevens-Johnson syndrome and autoimmune blistering
      diseases). These represent 0.47% of all ICU admissions, or approximately 2.1
      dermatological admissions per ICU per year. Overall mortality was 28.1% in the
      ICU and 40.0% in hospital. Length of stay in intensive care was longest for those
      with acute skin failure (median 4.7 days for ICU survivors and 5.1 days for ICU
      non-survivors). CONCLUSION: We have identified patients who not only require
      intensive care, but also dermatological care. Such patients have high mortality
      rates and long ICU stays within the spectrum of the UK ICU population, similar to
      other acute medical conditions. This highlights the importance of skin failure as
      a distinct entity comparable to other organ system failures.

PMID- 19105800
TI  - Case mix, outcome and activity for patients with severe acute kidney injury
      during the first 24 hours after admission to an adult, general critical care
      unit: application of predictive models from a secondary analysis of the ICNARC
      Case Mix Programme database.
AB  - INTRODUCTION: This study pools data from the UK Intensive Care National Audit and
      Research Center (ICNARC) Case Mix Programme (CMP) to evaluate the case mix,
      outcome and activity for 17,326 patients with severe acute kidney injury (AKI)
      occurring during the first 24 hours of admission to intensive care units (ICU).
      METHODS: Severe AKI admissions (defined as serum creatinine >/=300 mumol/l and/or
      urea >/=40 mmol/l during the first 24 hours) were extracted from the ICNARC CMP
      database of 276,326 admissions to UK ICUs from 1995 to 2004. Subgroups of
      oliguric and nonoliguric AKI were identified by daily urine output. Data on
      surgical status, survival and length of stay were also collected. Severity of
      illness scores and mortality prediction models were compared (UK Acute Physiology
      and Chronic Health Evaluation [APACHE] II, Stuivenberg Hospital Acute Renal
      Failure [SHARF] T0, SHARF II0 and the Mehta model). RESULTS: Severe AKI occurred
      in 17,326 out of 276,731 admissions (6.3%). The source of admission was
      nonsurgical in 83.7%. Sepsis was present in 47.3% and AKI was nonoliguric in
      63.9% of cases. Admission to ICU with severe AKI accounted for 9.3% of all ICU
      bed-days. Oliguric AKI was associated with longer length of stay for survivors
      and shorter length of stay for nonsurvivors compared with nonoliguric AKI.
      Oliguric AKI was associated with significantly greater ICU and hospital mortality
      (55.8% and 77.3%, respectively) compared with nonoliguric AKI (33.4% and 49.3%,
      respectively). Surgery during the 1 week before admission or during the first
      week in the CMP unit was associated with decreased odds of mortality. UK APACHE
      II and the Mehta scores under-predicted the number of deaths, whereas SHARF T0
      and SHARF II0 over-predicted the number of deaths. CONCLUSIONS: Severe AKI
      accounts for over 9% of all bed-days in adult, general ICUs, representing a
      considerable drain on resources. Although nonoliguric AKI continues to confer a
      survival benefit, overall survival from AKI in the ICU and survival to leave
      hospital remains poor. The use of APACHE II score measured during the first 24
      hours of ICU stay performs well as compared with SHARF T0, SHARF II0 and the
      Mehta score, but it lacks perfect calibration.

PMID- 19105801
TI  - Genetic analysis of the vitamin D receptor gene in two epithelial cancers:
      melanoma and breast cancer case-control studies.
AB  - BACKGROUND: Vitamin D serum levels have been found to be related to sun exposure
      and diet, together with cell differentiation, growth control and consequently,
      cancer risk. Vitamin D receptor (VDR) genotypes may influence cancer risk;
      however, no epidemiological studies in sporadic breast cancer (BC) or malignant
      melanoma (MM) have been performed in a southern European population. In this
      study, the VDR gene has been evaluated in two epithelial cancers BC and MM.
      METHODS: We have conducted an analysis in 549 consecutive and non-related
      sporadic BC cases and 556 controls, all from the Spanish population, and 283 MM
      cases and 245 controls. Genotyping analyses were carried out on four putatively
      functional SNPs within the VDR gene. RESULTS: An association with the minor
      allele A of the non-synonymous SNP rs2228570 (rs10735810, FokI, Met1Thr) was
      observed for BC, with an estimated odds ratio (OR) of 1.26 (95% CI = 1.02-1.57; p
      = 0.036). The synonymous variant rs731236 (TaqI) appeared to be associated with
      protection from BC (OR = 0.80, 95%CI = 0.64-0.99; p = 0.047). No statistically
      significant associations with MM were observed for any SNP. Nevertheless, sub
      group analyses revealed an association between rs2228570 (FokI) and absence of
      childhood sunburns (OR = 0.65, p = 0.003), between the 3'utr SNP rs739837 (BglI)
      and fair skin (OR = 1.31, p = 0.048), and between the promoter SNP rs4516035 and
      the more aggressive tumour location in head-neck and trunk (OR = 1.54, p =
      0.020). CONCLUSION: In summary, we observed associations between SNPs in the VDR
      gene and BC risk, and a comprehensive analysis using clinical and tumour
      characteristics as outcome variables has revealed potential associations with MM.
      These associations required confirmation in independent studies.

PMID- 19105802
TI  - Evaluation of deformity and hand function in cerebral palsy patients.
AB  - BACKGROUND: A cross-sectional study was performed to describe the upper limb
      deformity and function in cerebral palsy patients and to determine the
      correlation of deformity, spasticity, motor control, and sensation to hand
      function in the said population. MATERIALS AND METHODS: Thirty patients
      satisfying our inclusion criteria underwent physical, sensory, and functional
      assessment using a standard protocol. Physical assessment included documentation
      of the degree of spasticity, deformity and muscle control. Sensation was tested
      using static two-point discrimination test and stereognosis test. Melbourne
      Assessment of the Unilateral Upper Limb Function Test (MAULF), Functional Hand
      Grip Test (FHGT), and Functional Independence Measure for children (WeeFIM) were
      used to evaluate hand function. Deformity, spasticity, motor control, and
      sensation were analyzed for correlation with hand function using Pearson
      Correlation analysis. A p-value of less than 0.05 was considered statistically
      significant. RESULTS: Functional deficits of the hand increased with increasing
      severity of deformity and spasticity. Tetraplegics were most affected by
      spasticity, deformity, poor motor control, sensory and functional deficits.
      Triplegics, followed by diplegics had more functional upper limbs in terms of the
      MAULF and FHGT scores. Unilaterally affected patients (triplegics and
      hemiplegics) scored better in performance of activities of daily living. The
      MAULF and FHGT had a stronger correlation to deformity, spasticity and motor
      control compared to the WeeFIM. CONCLUSION: The degree of deformity, spasticity,
      sensory deficit, and motor control affected the hand function of a cerebral palsy
      patient significantly. The MAULF and FHGT more accurately represents hand
      function deficit in cerebral palsy patients.

PMID- 19105803
TI  - Outcome and patients' satisfaction after functional treatment of acute lateral
      ankle injuries at emergency departments versus family doctor offices.
AB  - BACKGROUND: In some Western countries, more and more patients seek initial
      treatment even for minor injuries at emergency units of hospitals. The initial
      evaluation and treatment as well as aftercare of these patients require large
      amounts of personnel and logistical resources, which are limited and costly,
      especially if compared to treatment by a general practitioner. In this study, we
      investigated whether outsourcing from our level 1 trauma center to a general
      practitioner has an influence on patient satisfaction and compliance. METHODS:
      This prospective, randomized study, included n = 100 patients who suffered from a
      lateral ankle ligament injury grade I-II (16, 17). After radiological exclusion
      of osseous lesions, the patients received early functional treatment and were
      shown physical therapy exercises to be done at home, without immobilization or
      the use of stabilizing ortheses. The patients were randomly assigned into two
      groups of 50 patients each: Group A (ER): Follow-up and final examination in the
      hospital's emergency unit. Group B (GP): Follow-up by general practitioner, final
      examination at hospital's emergency unit. The patients were surveyed regarding
      their satisfaction with the treatment and outcome of the treatment. RESULTS:
      Female and male patients were equally represented in both groups. The age of the
      patients ranged from 16 - 64 years, with a mean age of 34 years (ER) and 35 years
      (GP). 98% (n = 98) of all patients were satisfied with their treatment, and 93%
      (n = 93) were satisfied with the outcome. For these parameters no significant
      difference between the two groups could be noted (p = 0.7406 and 0.7631
      respectively). 39% of all patients acquired stabilizing ortheses like ankle
      braces (Aircast, Malleoloc etc.) on their own initiative. There was a not
      significant tendency for more self-acquired ortheses in the group treated by
      general practicioners (p = 0,2669). CONCLUSION: Patients who first present at the
      ER with a lateral ankle ligament injury grade I-II can be referred to a general
      practitioner for follow-up treatment without affecting patient satisfaction
      regarding treatment and treatment outcome.

PMID- 19105804
TI  - Psychological distress and associated factors among the attendees of traditional
      healing practices in Jinja and Iganga districts, Eastern Uganda: a cross
      sectional study.
AB  - BACKGROUND: Mental health problems are a major public health concern worldwide.
      Evidence shows that African communities, including Uganda, use both modern and
      traditional healing systems. There is limited literature about the magnitude of
      psychological distress and associated factors among attendees of traditional
      healing practices. This study aimed to determine the prevalence and associated
      factors of psychological distress among attendees of traditional healing
      practices in two districts in Uganda. METHODS: Face-to-face interviews with the
      Lusoga version of the Self Reporting Questionnaire (SRQ-20) were carried out with
      400 patients over the age of 18 years attending traditional healing in Iganga and
      Jinja districts in Eastern Uganda. Patients were recruited consecutively in all
      the traditional healers' shrines that could be visited in the area. Persons with
      6 or more positive responses to the SRQ were identified as having psychological
      distress. Prevalence was estimated and odds ratios of having psychological
      distress were obtained with multiple logistic regression analysis. RESULTS: 387
      questionnaire responses were analyzed. The prevalence of psychological distress
      in connection with attendance at the traditional healers' shrines was 65.1%.
      Having a co-wife and having more than four children were significantly associated
      with psyclogical distress. Among the socioeconomic indicators, lack of food and
      having debts were significantly associated with psychological distress. The
      distressed group was more likely to need explanations for ill health. Those who
      visited both the healer and a health unit were less likely to be distressed.
      CONCLUSION: This study provides evidence that a substantial proportion of
      attendees of traditional healing practices suffer from psychological distress.
      Associated factors include poverty, number of children, polygamy, reason for
      visiting the healer and use of both traditional healing and biomedical health
      units. These findings may be useful for policy makers and biomedical health
      workers for the engagement with traditional healers.

PMID- 19105805
TI  - Better estimation of protein-DNA interaction parameters improve prediction of
      functional sites.
AB  - BACKGROUND: Characterizing transcription factor binding motifs is a common
      bioinformatics task. For transcription factors with variable binding sites, we
      need to get many suboptimal binding sites in our training dataset to get accurate
      estimates of free energy penalties for deviating from the consensus DNA sequence.
      One procedure to do that involves a modified SELEX (Systematic Evolution of
      Ligands by Exponential Enrichment) method designed to produce many such
      sequences. RESULTS: We analyzed low stringency SELEX data for E. coli Catabolic
      Activator Protein (CAP), and we show here that appropriate quantitative analysis
      improves our ability to predict in vitro affinity. To obtain large number of
      sequences required for this analysis we used a SELEX SAGE protocol developed by
      Roulet et al. The sequences obtained from here were subjected to bioinformatic
      analysis. The resulting bioinformatic model characterizes the sequence
      specificity of the protein more accurately than those sequence specificities
      predicted from previous analysis just by using a few known binding sites
      available in the literature. The consequences of this increase in accuracy for
      prediction of in vivo binding sites (and especially functional ones) in the E.
      coli genome are also discussed. We measured the dissociation constants of several
      putative CAP binding sites by EMSA (Electrophoretic Mobility Shift Assay) and
      compared the affinities to the bioinformatics scores provided by methods like the
      weight matrix method and QPMEME (Quadratic Programming Method of Energy Matrix
      Estimation) trained on known binding sites as well as on the new sites from SELEX
      SAGE data. We also checked predicted genome sites for conservation in the related
      species S. typhimurium. We found that bioinformatics scores based on SELEX SAGE
      data does better in terms of prediction of physical binding energies as well as
      in detecting functional sites. CONCLUSION: We think that training binding site
      detection algorithms on datasets from binding assays lead to better prediction.
      The improvements in accuracy came from the unbiased nature of the SELEX dataset
      rather than from the number of sites available. We believe that with progress in
      short-read sequencing technology, one could use SELEX methods to characterize
      binding affinities of many low specificity transcription factors.

PMID- 19105806
TI  - Could sound be used as a strategy for reducing symptoms of perceived motion
      sickness?
AB  - BACKGROUND: Working while exposed to motions, physically and psychologically
      affects a person. Traditionally, motion sickness symptom reduction has implied
      use of medication, which can lead to detrimental effects on performance. Non
      pharmaceutical strategies, in turn, often require cognitive and perceptual
      attention. Hence, for people working in high demand environments where it is
      impossible to reallocate focus of attention, other strategies are called upon.
      The aim of the study was to investigate possible impact of a mitigation strategy
      on perceived motion sickness and psychophysiological responses, based on an
      artificial sound horizon compared with a non-positioned sound source. METHODS:
      Twenty-three healthy subjects were seated on a motion platform in an artificial
      sound horizon or in non-positioned sound, in random order with one week interval
      between the trials. Perceived motion sickness (Mal), maximum duration of exposure
      (ST), skin conductance, blood volume pulse, temperature, respiration rate, eye
      movements and heart rate were measured continuously throughout the trials.
      RESULTS: Mal scores increased over time in both sound conditions, but the
      artificial sound horizon, applied as a mitigation strategy for perceived motion
      sickness, showed no significant effect on Mal scores or ST. The number of
      fixations increased with time in the non-positioned sound condition. Moreover,
      fixation time was longer in the non-positioned sound condition compared with
      sound horizon, indicating that the subjects used more time to fixate and, hence,
      assumingly made fewer saccades. CONCLUSION: A subliminally presented artificial
      sound horizon did not significantly affect perceived motion sickness,
      psychophysiological variables or the time the subjects endured the motion
      sickness triggering stimuli. The number of fixations and fixation times increased
      over time in the non-positioned sound condition.

PMID- 19105807
TI  - De novo complex intra chromosomal rearrangement after ICSI: characterisation by
      BACs micro array-CGH.
AB  - BACKGROUND: In routine Assisted Reproductive Technology (ART) men with severe
      oligozoospermia or azoospermia should be informed about the risk of de novo
      congenital or chromosomal abnormalities in ICSI program. Also the benefits of
      preimplantation or prenatal genetic diagnosis practice need to be explained to
      the couple. METHODS: From a routine ICSI attempt, using ejaculated sperm from
      male with severe oligozoospermia and having normal karyotype, a 30 years old
      pregnant woman was referred to prenatal diagnosis in the 17th week for
      bichorionic biamniotic twin gestation. Amniocentesis was performed because of the
      detection of an increased foetal nuchal translucency for one of the fetus by the
      sonographic examination during the 12th week of gestation (WG). Chromosome and
      DNA studies of the fetus were realized on cultured amniocytes RESULTS:
      Conventional, molecular cytogenetic and microarray CGH experiments allowed us to
      conclude that the fetus had a de novo pericentromeric inversion associated with a
      duplication of the 9p22.1-p24 chromosomal region, 46,XY,invdup(9)(p22.1p24)
      [arrCGH 9p22.1p24 (RP11-130C19 --> RP11-87O1)x3]. As containing the critical 9p22
      region, our case is in coincidence with the general phenotype features of the
      partial trisomy 9p syndrome with major growth retardation, microcephaly and
      microretrognathia. CONCLUSION: This de novo complex chromosome rearrangement
      illustrates the possible risk of chromosome or gene defects in ICSI program and
      the contribution of array-CGH for mapping rapidly de novo chromosomal imbalance.

PMID- 19105808
TI  - Comparison of the MicroScan, VITEK 2, and Crystal GP with 16S rRNA sequencing and
      MicroSeq 500 v2.0 analysis for coagulase-negative Staphylococci.
AB  - BACKGROUND: Three phenotypic identification systems (MicroScan, VITEK 2, and
      Crystal GP) were evaluated for their accuracy to identify coagulase-negative
      staphylococci (CNS). A total of 120 clinical isolates confirmed to be CNS via 16S
      rRNA sequencing and analysis with the MicroSeq 500 v2.0 database were assessed.
      RESULTS: The MicroScan, VITEK 2, and Crystal GP systems correctly identified
      82.5%, 87.5%, and 67.5% of the isolates, respectively. Misidentification was the
      main problem in MicroScan (10.8%) and Crystal GP (23.3%) systems, whereas the
      main problem of VITEK 2 was low-level discrimination (7.5%). CONCLUSION: None of
      the 3 phenotypic systems tested could accurately and reliably identify CNS at the
      species level. Further verifications such as biochemical testing or 16S rRNA
      sequencing together with analysis using a comparable database might be helpful in
      this regard.

PMID- 19105809
TI  - Termination of pregnancy due to Thalassemia major, Hemophilia, and Down's
      syndrome: the views of Iranian physicians.
AB  - BACKGROUND: Genetic disorders due to kindred marriages are common medical
      conditions in Iran; however, the legal aspects of abortion remain controversial.
      This study was undertaken to determine physicians' opinions regarding the
      termination of pregnancy for three genetic diseases: thalassemia major,
      hemophilia, and Down's syndrome. METHODS: A questionnaire was administered to
      selected physicians by stratified random sampling to determine the following:
      age, gender, knowledge about prenatal diagnosis of diseases in high risk
      pregnancies, agreement with abortion, recommended gestational age for abortion,
      and, if opposed to abortion, the reason. RESULTS: Of 323 physicians, who
      participated in the study, 91.3(295), 40.6(131), and 78.6%(254) were in agreement
      and 8.7(28), 59.4(192), and 21.4%(69) were opposed to abortion for thalassemia
      major, hemophilia, and Down's syndrome, respectively. Among 289 physicians
      opposed to abortion in respect of each of all three conditions, the following
      reasons were cited: religion, 18; emotional, 10; quality of care, 23; hope to
      find a new treatment option in the future, 103; miscellaneous reasons, 6; and a
      combination of these reasons, 129. Among 680 physicians in agreement with
      abortion in relation to all of the diseases, 4.6%(31) were agreed with abortion
      in less than 12 weeks gestation, 79.2%(538) in less than 16 weeks gestation,
      5.6%(38) in less than 20 weeks gestation, 2.2%(15) in less than 24 weeks
      gestation, and 8.4%(58) were agreed with beyond the 24 weeks of gestational age.
      CONCLUSION: The majority of physicians were in agreement with abortion for
      thalassemia major and Down's syndrome because of the overall prognosis, but
      opposed to abortion for hemophilia.

PMID- 19105810
TI  - Mycobacterium tuberculosis interactome analysis unravels potential pathways to
      drug resistance.
AB  - BACKGROUND: Emergence of drug resistant varieties of tuberculosis is posing a
      major threat to global tuberculosis eradication programmes. Although several
      approaches have been explored to counter resistance, there has been limited
      success due to a lack of understanding of how resistance emerges in bacteria upon
      drug treatment. A systems level analysis of the proteins involved is essential to
      gain insights into the routes required for emergence of drug resistance. RESULTS:
      We derive a genome-scale protein-protein interaction network for Mycobacterium
      tuberculosis H37Rv from the STRING database, with proteins as nodes and
      interactions as edges. A set of proteins involved in both intrinsic and extrinsic
      drug resistance mechanisms are identified from literature. We then compute
      shortest paths from different drug targets to the set of resistance proteins in
      the protein-protein interactome, to derive a sub-network relevant to study
      emergence of drug resistance. The shortest paths are then scored and ranked based
      on a new scheme that considers (a) drug-induced gene upregulation data, from
      microarray experiments reported in literature, for the individual nodes and (b)
      edge-hubness, a network parameter which signifies centrality of a given edge in
      the network. High-scoring paths identified from this analysis indicate most
      plausible pathways for the emergence of drug resistance. Different targets appear
      to have different propensities for four drug resistance mechanisms. A new concept
      of 'co-targets' has been proposed to counter drug resistance, co-targets being
      defined as protein(s) that need to be simultaneously inhibited along with the
      intended target(s), to check emergence of resistance to a given drug. CONCLUSION:
      The study leads to the identification of possible pathways for drug resistance,
      providing novel insights into the problem of resistance. Knowledge of important
      proteins in such pathways enables identification of appropriate 'co-targets',
      best examples being RecA, Rv0823c, Rv0892 and DnaE1, for drugs targeting the
      mycolic acid pathway. Insights obtained about the propensity of a drug to trigger
      resistance will be useful both for more careful identification of drug targets as
      well as to identify target-co-target pairs, both implementable in early stages of
      drug discovery itself. This approach is also inherently generic, likely to
      significantly impact drug discovery.

PMID- 19105811
TI  - The lipoxygenase gene family: a genomic fossil of shared polyploidy between
      Glycine max and Medicago truncatula.
AB  - BACKGROUND: Soybean lipoxygenases (Lxs) play important roles in plant resistance
      and in conferring the distinct bean flavor. Lxs comprise a multi-gene family that
      includes GmLx1, GmLx2 and GmLx3, and many of these genes have been characterized.
      We were interested in investigating the relationship between the soybean
      lipoxygenase isozymes from an evolutionary perspective, since soybean has
      undergone two rounds of polyploidy. Here we report the tetrad genome structure of
      soybean Lx regions produced by ancient and recent polyploidy. Also, comparative
      genomics with Medicago truncatula was performed to estimate Lxs in the common
      ancestor of soybean and Medicago. RESULTS: Two Lx regions in Medicago truncatula
      showing synteny with soybean were analyzed. Differential evolutionary rates
      between soybean and Medicago were observed and the median Ks values of Mt-Mt, Gm
      Mt, and Gm-Gm paralogs were determined to be 0.75, 0.62, and 0.46, respectively.
      Thus the comparison of Gm-Mt paralogs (Ks = 0.62) and Gm-Mt orthologs (Ks = 0.45)
      supports the ancient duplication of Lx regions in the common ancestor prior to
      the Medicago-Glycine split. After speciation, no Lx regions generated by another
      polyploidy were identified in Medicago. Instead tandem duplication of Lx genes
      was observed. On the other hand, a lineage-specific duplication occurred in
      soybean resulting in two pairs of Lx regions. Each pair of soybean regions was co
      orthologous to one Lx region in Medicago. A total of 34 Lx genes (15 MtLxs and 19
      GmLxs) were divided into two groups by phylogenetic analysis. Our study shows
      that the Lx gene family evolved from two distinct Lx genes in the most recent
      common ancestor. CONCLUSION: This study analyzed two pairs of Lx regions
      generated by two rounds of polyploidy in soybean. Each pair of soybean
      homeologous regions is co-orthologous to one region of Medicago, demonstrating
      the quartet structure of the soybean genome. Differential evolutionary rates
      between soybean and Medicago were observed; thus optimized rates of Ks per year
      should be applied for accurate estimation of coalescence times to each case of
      comparison: soybean-soybean, soybean-Medicago, or Medicago-Medicago. In
      conclusion, the soybean Lx gene family expanded by ancient polyploidy prior to
      taxon divergence, followed by a soybean- specific duplication and tandem
      duplications, respectively.

PMID- 19105812
TI  - The impact of overweight and obesity on health-related quality of life in
      childhood--results from an intervention study.
AB  - BACKGROUND: The negative impact of overweight (including obesity) and related
      treatment on children's and adolescents' health-related quality of life (HRQoL)
      has been shown in few specific samples thus far. We examined HRQoL and emotional
      well-being in overweight children from an outpatient treatment sample as well as
      changes of these parameters during treatment. METHODS: In a cross-sectional
      design, self-reported HRQoL of 125 overweight (including obese) children who
      contacted a treatment facility, but had not yet receive treatment, were compared
      to 172 children from randomly selected schools using independent two-sample t
      tests. Additionally, in a longitudinal design, the overweight children were
      retested by administering the same questionnaire at the end of the intervention
      (after one year). It included measures such as the body mass index (BMI), the
      general health item (GHI), the KINDLR, and the Child Dynamic Health Assessment
      Scale (ChildDynHA). Comparisons were based on dependent t-tests and the Wilcoxon
      signed-rank test. RESULTS: Overweight children showed statistically significant
      impairment in the GHI (Cohen's d = 0.59) and emotional well-being (ChildDynha) (d
      = 0.33) compared to the school children. With respect to HRQoL, the friends
      dimension of the KINDLR was significantly impaired in the overweight group (d =
      0.33). However, no impairment was found for the total HRQoL score or other KINDLR
      subdimensions. Regarding the longitudinal part of our study, most of the children
      improved their BMI, but the majority (87.5%) remained overweight. Nevertheless,
      the participants' perceived health, emotional well-being, and generic as well as
      disease-specific HRQoL improved during intervention. CONCLUSION: The findings
      emphasize the importance of patient-reported outcomes such as HRQoL. Even though
      overweight and obesity might accompany most of the children throughout their
      lifetime, the impairment associated with this chronic condition can be
      considerably reduced. Opportunities of health promotion in overweight/obese
      children and adolescents are discussed.

PMID- 19105813
TI  - Comparative kinomics of human and chimpanzee reveal unique kinship and functional
      diversity generated by new domain combinations.
AB  - BACKGROUND: Phosphorylation by protein kinases is a common event in many cellular
      processes. Further, many kinases perform specialized roles and are regulated by
      non-kinase domains tethered to kinase domain. Perturbation in the regulation of
      kinases leads to malignancy. We have identified and analysed putative protein
      kinases encoded in the genome of chimpanzee which is a close evolutionary
      relative of human. RESULT: The shared core biology between chimpanzee and human
      is characterized by many orthologous protein kinases which are involved in
      conserved pathways. Domain architectures specific to chimp/human kinases have
      been observed. Chimp kinases with unique domain architectures are characterized
      by deletion of one or more non-kinase domains in the human kinases.
      Interestingly, counterparts of some of the multi-domain human kinases in chimp
      are characterized by identical domain architectures but with kinase-like non
      kinase domain. Remarkably, out of 587 chimpanzee kinases no human orthologue with
      greater than 95% sequence identity could be identified for 160 kinases.
      Variations in chimpanzee kinases compared to human kinases are brought about also
      by differences in functions of domains tethered to the catalytic kinase domain.
      For example, the heterodimer forming PB1 domain related to the fold of
      ubiquitin/Ras-binding domain is seen uniquely tethered to PKC-like chimpanzee
      kinase. CONCLUSION: Though the chimpanzee and human are evolutionary very close,
      there are chimpanzee kinases with no close counterpart in the human suggesting
      differences in their functions. This analysis provides a direction for
      experimental analysis of human and chimpanzee protein kinases in order to enhance
      our understanding on their specific biological roles.

PMID- 19105814
TI  - Hip fracture incidence in the elderly in Austria: an epidemiological study
      covering the years 1994 to 2006.
AB  - BACKGROUND: Hip fractures in the elderly are a major public health burden. Data
      concerning secular trends of hip fracture incidence show divergent results for
      age, sex and regions. In Austria, the hip fracture incidence in the elderly
      population and trends have not been analysed yet. METHODS: Hip fractures in the
      population of 50 years and above were identified from 1994 to 2006 using the
      national hospital discharge register. Crude incidences (IR) per 100,000 person
      years and standardised incidences related to the European population 2006 were
      analysed. Estimate of age-sex-adjusted changes was determined using Poisson
      regression (incidence rate ratios, IRRs). RESULTS: The number of hospital
      admissions due to hip fracture increased from a total number of 11,694 in 1994 to
      15,987 in 2006. Crude incidences rates (IR) per 100.000 for men increased from
      244.3 (95% confidence interval (CI) 234.8 to 253.7) in 1994 to IR 330.8 (95% CI
      320.8 to 340.9) in 2006 and for women from 637.3 (95% CI 624.2 to 650.4) in 1994
      to IR 758.7 (95% CI 745.0 to 772.4) in 2006. After adjustment for age and sex the
      annual hip fracture incidence increase was only small but statistically
      significant (IRR per year 1.01, 95% CI 1.01 to 1.01, p < 0.01). Change of IRR
      over the 12 years study period was 13%. It was significantly higher for men (IRR
      over 12 years 1.21, 95% CI 1.16 to 1.27) than for women (IRR over 12 years 1.10,
      95% CI 1.06 to 1.14) (interaction: p = 0.03). CONCLUSION: In contrast to findings
      in other countries there is no levelling-off or downward trend of hip fracture
      incidence from 1994 to 2006 in the Austrian elderly population. Further
      investigations should aim to evaluate the underlying causes in order to plan
      effective hip fracture reduction programmes.

PMID- 19105815
TI  - The association between renal function and structural parameters: a pig study.
AB  - BACKGROUND: The objective was to investigate the association between renal
      structural parameters and renal function. The structural parameters were renal
      cortical volume, total renal volume, number of glomeruli, and total glomerular
      volume, and renal function was expressed by the single kidney GFR (skGFR).
      Investigations were performed using both healthy and chronically diseased
      kidneys. We investigated which of the structural parameters showed the best
      correlation to renal function and evaluated the possibility of predicting the
      renal function from structural parameters. METHODS: Twenty-four pigs, twelve with
      healthy kidneys and twelve with diseased kidneys, underwent skGFR measurements.
      Nephrectomies were performed and structural parameters were estimated using
      stereological procedures. The correlation between the structural parameters and
      skGFR was analysed by Pearson's correlation test. The prediction of skGFR from
      structural parameters was analysed by a linear regression test. RESULTS: In
      general, we demonstrated a good correlation between structural parameters and
      skGFR. When all kidneys were evaluated together Pearson's correlation coefficient
      between skGFR and any stereological parameter was above 0.60 and highly
      significant (p < 0.001), and with r-values ranging from 0.62 regarding number of
      glomeruli, to 0.78 regarding cortical volume. The best correlation was found
      between cortical volume and skGFR. Prediction of single kidney GFR from any
      structural parameter showed to be quite imprecise. CONCLUSION: The observed
      correlations between structural parameters and renal function suggest that these
      parameters may potentially be useful as surrogate markers of the renal function.
      At present, however, precise prediction of renal function based on a single
      structural parameter seems hard to obtain.

PMID- 19105816
TI  - Hairy-root organ cultures for the production of human acetylcholinesterase.
AB  - BACKGROUND: Human cholinesterases can be used as a bioscavenger of
      organophosphate toxins used as pesticides and chemical warfare nerve agents. The
      practicality of this approach depends on the availability of the human enzymes,
      but because of inherent supply and regulatory constraints, a suitable production
      system is yet to be identified. RESULTS: As a promising alternative, we report
      the creation of "hairy root" organ cultures derived via Agrobacterium rhizogenes
      mediated transformation from human acetylcholinesterase-expressing transgenic
      Nicotiana benthamiana plants. Acetylcholinesterase-expressing hairy root cultures
      had a slower growth rate, reached to the stationary phase faster and grew to
      lower maximal densities as compared to wild type control cultures.
      Acetylcholinesterase accumulated to levels of up to 3.3% of total soluble
      protein, ~3 fold higher than the expression level observed in the parental plant.
      The enzyme was purified to electrophoretic homogeneity. Enzymatic properties were
      nearly identical to those of the transgenic plant-derived enzyme as well as to
      those of mammalian cell culture derived enzyme. Pharmacokinetic properties of the
      hairy-root culture derived enzyme demonstrated a biphasic clearing profile. We
      demonstrate that master banking of plant material is possible by storage at 4
      degrees C for up to 5 months. CONCLUSION: Our results support the feasibility of
      using plant organ cultures as a successful alternative to traditional transgenic
      plant and mammalian cell culture technologies.

PMID- 19105817
TI  - A combination of right ventricular hypertrabeculation/noncompaction and
      arrhythmogenic right ventricular cardiomyopathy: a syndrome?
AB  - A combination of ARVC and RV NVM/HVM, which is extremely rare, to our knowledge,
      is never reported. RV NVM/HVM could be the cause and consequence of ARVC, or RV
      NVM/HVM and ARVC could be a consequence of a certain undetermined cause. It must
      be kept in mind, however, that the interaction of NVM/HVM and ARVC could be in
      part of pathophysiology mechanism of the combination even if as a consequence of
      an underlying genetic factor.

PMID- 19105818
TI  - Echocardiography in the diagnosis left ventricular noncompaction.
AB  - Echocardiography is the method of choice to establish a diagnosis and determine a
      treatment plan for patients with noncompaction of ventricular myocardium (NVM).
      The 2-dimentional echocardiography, 3-dimentional echocardiography, color Doppler
      echocardiography and contrast-enhanced echocardiography are of critical
      importance for diagnosis and family screening of NVM.

PMID- 19105819
TI  - A DNA topoisomerase IB in Thaumarchaeota testifies for the presence of this
      enzyme in the last common ancestor of Archaea and Eucarya.
AB  - DNA topoisomerase IB (TopoIB) was thought for a long time to be a eukaryotic
      specific enzyme. A shorter version was then found in viruses and later on in
      several bacteria, but not in archaea. Here, we show that a eukaryotic-like TopoIB
      is present in the recently sequenced genomes of two archaea of the newly proposed
      phylum Thaumarchaeota. Phylogenetic analyses suggest that a TopoIB was present in
      the last common ancestor of Archaea and Eucarya. This finding indicates that the
      last common ancestor of Archaea and Eucarya may have harboured a DNA genome.

PMID- 19105821
TI  - Isolated specialist or system integrated physician--different views on sickness
      certification among orthopaedic surgeons: an interview study.
AB  - BACKGROUND: Sickness certification is a frequent and sometimes problematic task
      for orthopaedic surgeons.Our aim was to explore how orthopaedic surgeons view
      their sick-listing commission and sick-listing practice. METHODS: Semi-structured
      interviews with seventeen orthopaedic surgeons from five orthopaedic clinics in
      four Swedish counties. The focus was on the experiences of these physicians in
      relation to handling of sickness certification. Phenomenographic analysis was
      performed to reveal differences in existing views. RESULTS: The orthopaedic
      surgeons' views on sick-listing seemed mainly to be a consequence of how they
      perceived their role in the healthcare system. Three categories were found: The
      "isolated specialists", whose work and responsibilities were confined to the
      orthopaedic clinic, and did not really include sickness certification; the
      "orthopaedic advisers", who saw themselves mainly as advice-givers in the general
      health care system and perceived sickness certification as part of their job; the
      "system-integrated physicians", who perceived the orthopaedic clinic as one part
      of the healthcare system and whose ultimate goal was to get the patient well
      functioning in her life again with regained work ability, seeing sick-listing as
      one of the instruments to achieve this. Some informants described difficulties in
      handling conflicting opinions with patients in relation to the need for sick
      leave. CONCLUSION: Orthopaedic surgeons certify a large proportion of total
      sickness benefits. Some orthopaedic surgeons may certify sickness benefits sub
      optimally for patients and society due to a narrow view of their role in the
      health care system or due to poor skills in handling discordant opinions with the
      patient. This problem can be addressed at the level of the individual physician
      and at the system level.

PMID- 19105820
TI  - Mapping of the transcription start site (TSS) and identification of SNPs in the
      bovine neuropeptide Y (NPY) gene.
AB  - BACKGROUND: Neuropeptide Y is a key neurotransmitter of the central nervous
      system which plays a vital role in the feed energy homeostasis in mammals.
      Mutations in the regulatory and coding regions of the bovine NPY gene can
      potentially affect the neuronal regulation of appetite and feeding behaviour in
      cattle. The objectives of this experiment were to: a) fully characterize the
      bovine NPY gene transcript and b) identify the SNP diversity in both coding and
      non-coding regions of the NPY gene in a panel of Bos taurus and B. indicus
      cattle. RESULTS: Bovine NPY gene consists of four exons (99, 188, 81 and 195
      nucleotides) and three introns. The promoter region of the NPY gene consists of
      TATA and GC boxes which are separated from the transcription start site (TSS) by
      29 and ~100 nt, respectively. Analyses of the tissue specific expression of the
      bovine NPY gene revealed the presence of highly abundant NPY gene transcripts in
      the arcuate nucleus, cerebral and cerebellar regions of the bovine brain. We
      identified a total of 59 SNPs in the 8.4 kb region of the bovine NPY gene. Seven
      out of nine total SNPs in the promoter region affect binding of putative
      transcription factors. A high level of nucleotide diversity was evident in the
      promoter regions (2.84 x 10(-3)) compared to the exonic (1.44 x 10(-3)), intronic
      (1.30 x 10(-3)) and 3' untranslated (1.26 x 10(-3)) regions. CONCLUSION: The SNPs
      identified in different regions of bovine NPY gene may serve as a basis for
      understanding the regulation of the expression of the bovine NPY gene under a
      variety of physiological conditions and identification of genotypes with high
      feed energy conversion efficiency.

PMID- 19105822
TI  - Association of alpha1a-adrenergic receptor polymorphism and blood pressure
      phenotypes in the Brazilian population.
AB  - BACKGROUND: The alpha1A-adrenergic receptor (alpha1A-AR) regulates the cardiac
      and peripheral vascular system through sympathetic activation. Due to its
      important role in the regulation of vascular tone and blood pressure, we aimed to
      investigate the association between the Arg347Cys polymorphism in the alpha1A-AR
      gene and blood pressure phenotypes, in a large sample of Brazilians from an urban
      population. METHODS: A total of 1568 individuals were randomly selected from the
      general population of the Vitoria City metropolitan area. Genetic analysis of the
      Arg347Cys polymorphism was conducted by polymerase chain reaction/restriction
      fragment length polymorphism. We have compared cardiovascular risk variables and
      genotypes using ANOVA, and Chi-square test for univariate comparisons and
      logistic regression for multivariate comparisons. RESULTS: Association analysis
      indicated a significant difference between genotype groups with respect to
      diastolic blood pressure (p = 0.04), but not systolic blood pressure (p = 0.12).
      In addition, presence of the Cys/Cys genotype was marginally associated with
      hypertension in our population (p = 0.06). Significant interaction effects were
      observed between the studied genetic variant, age and physical activity. Presence
      of the Cys/Cys genotype was associated with hypertension only in individuals with
      regular physical activity (odds ratio = 1.86; p = 0.03) or younger than 45 years
      (odds ratio = 1.27; p = 0.04). CONCLUSION: Physical activity and age may
      potentially play a role by disclosing the effects of the Cys allele on blood
      pressure. According to our data it is possible that the Arg347Cys polymorphism
      can be used as a biomarker to disease risk in a selected group of individuals.

PMID- 19105823
TI  - Exposing the key functions of a complex intervention for shared care in mental
      health: case study of a process evaluation.
AB  - BACKGROUND: Complex interventions have components which can vary in different
      contexts. Using the Realistic Evaluation framework, this study investigates how a
      complex health services intervention led to developments in shared care for
      people with long-term mental illness. METHODS: A retrospective qualitative
      interview study was carried out alongside a randomised controlled trial. The
      multi-faceted intervention supported by facilitators aimed to develop systems for
      shared care. The study was set in London. Participants included 46 practitioners
      and managers from 12 participating primary health care teams and their associated
      community mental health teams. Interviews focussed on how and why out comes were
      achieved, and were analysed using a framework incorporating context and
      intervening mechanisms. RESULTS: Thirty-one interviews were completed to create
      12 case studies. The enquiry highlighted the importance of the catalysing, doing
      and reviewing functions of the facilitation process. Other facets of the
      intervention were less dominant. The intervention catalysed the allocation of
      link workers and liaison arrangements in nearly all practices. Case discussions
      between link workers and GPs improved individual care as well as helping link
      workers become part of the primary care team; but sustained integration into the
      team depended both on flexibility and experience of the link worker, and upon
      selection of relevant patients for the case discussions. The doing function of
      facilitators included advice and, at times, manpower, to help introduce
      successful systems for reviewing care, however time spent developing IT systems
      was rarely productive. The reviewing function of the intervention was weak and
      sometimes failed to solve problems in the development of liaison or recall.
      CONCLUSION: Case discussions and improved liaison at times of crisis, rather than
      for proactive recall, were the key functions of shared care contributing to the
      success of Mental Health Link. This multifaceted intervention had most impact
      through catalysing and doing, whereas the reviewing function of the facilitation
      was weak, and other components were seen as less important. Realistic Evaluation
      provided a useful theoretical framework for this process evaluation, by allowing
      a specific focus on context. Although complex interventions might appear 'out of
      control', due to their varied manifestation in different situations, context
      sensitive process evaluations can help identify the intervention's key functions.

PMID- 19105824
TI  - Thymidylate synthase, dihydropyrimidine dehydrogenase, ERCC1, and thymidine
      phosphorylase gene expression in primary and metastatic gastrointestinal
      adenocarcinoma tissue in patients treated on a phase I trial of oxaliplatin and
      capecitabine.
AB  - BACKGROUND: Over-expression of thymidylate synthase (TS) and dihydropyrimidine
      dehydrogenase (DPD) in tumor tissue is associated with insensitivity to 5
      fluorouracil (5-FU). Over-expression of ERCC1 correlates with insensitivity to
      oxaliplatin (OX) therapy, while high thymidine phosphorylase (TP) levels predict
      for increased sensitivity to capecitabine (Xel). METHODS: Biopsies of metastatic
      tumor were taken before OX (130 mg/m2 day 1) given with Xel (1200-3000 mg/m2 in
      two divided doses days 1-5 and 8-12) every 3-weeks. Micro-dissected metastatic
      and primary tumors were analyzed for relative gene expression by real-time
      quantitative polymerase chain reaction. The clinical protocol prospectively
      identified the molecular targets of interest that would be tested. Endpoints for
      the molecular analyses were correlation of median, first and third quartiles for
      relative gene expression of each target with response, time to treatment failure
      (TTF), and survival. RESULTS: Among 91 patients participating in this trial; 97%
      had colorectal cancer. The median number of prior chemotherapy regimens was 2,
      and most had prior 5-FU and irinotecan. In paired samples, median mRNA levels
      were significantly higher in metastatic versus primary tumor (-fold): TS (1.9),
      DPD (3.8), ERCC1 (2.1) and TP (1.6). A strong positive correlation was noted
      between DPD and TP mRNA levels in both primary (r = 0.693, p < 0.0005) and
      metastatic tissue (r = 0.697, p < 0.00001). There was an association between TS
      gene expression and responsive and stable disease: patients whose intratumoral TS
      mRNA levels were above the median value had significantly greater risk of early
      disease progression (43% vs 17%), but this did not translate into a significant
      difference in TTF. ERCC1 gene expression above the third quartile was associated
      with a shorter TTF (median 85 vs 162 days, p = 0.046). Patients whose TS mRNA
      levels in metastatic tumor tissue were below the median had a longer overall
      survival (median 417 vs 294 days, p = 0.042). CONCLUSION: Target gene expression
      in primary tumor was significantly lower than that in paired metastatic tissue.
      High ERCC1 mRNA levels in metastatic tumor was associated with a shorter TTF.
      Lower expression of TS mRNA correlated with a lower chance of early PD with XelOX
      therapy and improved overall survival.

PMID- 19105825
TI  - The impact of image dynamic range on texture classification of brain white
      matter.
AB  - BACKGROUND: The Greylevel Cooccurrence Matrix method (COM) is one of the most
      promising methods used in Texture Analysis of Magnetic Resonance Images. This
      method provides statistical information about the spatial distribution of
      greylevels in the image which can be used for classification of different tissue
      regions. Optimizing the size and complexity of the COM has the potential to
      enhance the reliability of Texture Analysis results. In this paper we investigate
      the effect of matrix size and calculation approach on the ability of COM to
      discriminate between peritumoral white matter and other white matter regions.
      METHOD: MR images were obtained from patients with histologically confirmed brain
      glioblastoma using MRI at 3-T giving isotropic resolution of 1 mm3. Three Regions
      of Interest (ROI) were outlined in visually normal white matter on three image
      slices based on relative distance from the tumor: one peritumoral white matter
      region and two distant white matter regions on both hemispheres. Volumes of
      Interest (VOI) were composed from the three slices. Two different calculation
      approaches for COM were used: i) Classical approach (CCOM) on each individual
      ROI, and ii) Three Dimensional approach (3DCOM) calculated on VOIs. For, each
      calculation approach five dynamic ranges (number of greylevels N) were
      investigated (N = 16, 32, 64, 128, and 256). RESULTS: Classification showed that
      peritumoral white matter always represents a homogenous class, separate from
      other white matter, regardless of the value of N or the calculation approach
      used. The best test measures (sensitivity and specificity) for average CCOM were
      obtained for N = 128. These measures were also optimal for 3DCOM with N = 128,
      which additionally showed a balanced tradeoff between the measures. CONCLUSION:
      We conclude that the dynamic range used for COM calculation significantly
      influences the classification results for identical samples. In order to obtain
      more reliable classification results with COM, the dynamic range must be
      optimized to avoid too small or sparse matrices. Larger dynamic ranges for COM
      calculations do not necessarily give better texture results; they might increase
      the computation costs and limit the method performance.

PMID- 19105826
TI  - A novel method for neck coordination exercise--a pilot study on persons with
      chronic non-specific neck pain.
AB  - BACKGROUND: Chronic neck pain is a common problem and is often associated with
      changes in sensorimotor functions, such as reduced proprioceptive acuity of the
      neck, altered coordination of the cervical muscles, and increased postural sway.
      In line with these findings there are studies supporting the efficacy of
      exercises targeting different aspects of sensorimotor function, for example
      training aimed at improving proprioception and muscle coordination. To further
      develop this type of exercises we have designed a novel device and method for
      neck coordination training. The aim of the study was to investigate the clinical
      applicability of the method and to obtain indications of preliminary effects on
      sensorimotor functions, symptoms and self-rated characteristics in non-specific
      chronic neck pain METHODS: The study was designed as an uncontrolled clinical
      trial including fourteen subjects with chronic non-specific neck pain. A new
      device was designed to allow for an open skills task with adjustable difficulty.
      With visual feedback, subjects had to control the movement of a metal ball on a
      flat surface with a rim strapped on the subjects' head. Eight training sessions
      were performed over a four week period. Skill acquisition was measured throughout
      the intervention period. After intervention subjects were interviewed about their
      experience of the exercise and pain and sensorimotor functions, including the
      fast and slow components of postural sway and jerkiness-, range-, position sense
      , movement time- and velocity of cervical rotation, were measured. At six-month
      follow up, self-rated pain, health and functioning was collected. RESULTS: The
      subjects improved their skill to perform the exercise and were overall positive
      to the method. No residual negative side-effects due to the exercise were
      reported. After intervention the fast component of postural sway (p = 0.019) and
      jerkiness of cervical rotation (p = 0.032) were reduced. The follow up showed
      decreased disability (one out of three indices) and fear of movement, and
      increased general health (three out of eight dimensions). CONCLUSION: The results
      support the clinical applicability of the method. The improvements in
      sensorimotor functions may suggest transfer from the exercise to other, non-task
      specific motor functions and justifies a future randomized controlled trial.

PMID- 19105827
TI  - Long-term topical cyclosporin A therapy in Thygeson's superficial punctate
      keratitis: a case report.
AB  - PURPOSE: To describe a patient with Thygeson's superficial punctate keratitis
      successfully treated with long-term cyclosporin A. CASE PRESENTATION: A 15-year
      old boy presented with long-term ocular symptoms of foreign body sensation,
      burning, irritation, tearing, and transient photophobia. One year's treatment
      with steroidal agents had led to only partial improvement. Clinical and
      laboratory evaluation yielded a diagnosis of Thygeson's superficial punctate
      keratitis. Treatment with 0.5% topical cyclosporin A for the last 4.5 years has
      been associated with symptom resolution and corneal clearing, without side
      effects. CONCLUSION: Topical cyclosporin A seems to effective and safe for the
      treatment of Thygeson's superficial punctuate keratitis and should be considered
      in selective cases when topical steroids fail or in there is a high risk of
      complications from long-term steroid treatment. Considering the chronicity of
      Thygeson's superficial punctate keratitis, further prospective studies of long
      term cyclosporine A treatment are needed.

PMID- 19105828
TI  - Characteristics of patients initiating raloxifene compared to those initiating
      bisphosphonates.
AB  - BACKGROUND: Both raloxifene and bisphosphonates are indicated for the prevention
      and treatment of postmenopausal osteoporosis, however these medications have
      different efficacy and safety profiles. It is plausible that physicians would
      prescribe these agents to optimize the benefit/risk profile for individual
      patients. The objective of this study was to compare demographic and clinical
      characteristics of patients initiating raloxifene with those of patients
      initiating bisphosphonates for the prevention and treatment of osteoporosis.
      METHODS: This study was conducted using a retrospective cohort design. Female
      beneficiaries (45 years and older) with at least one claim for raloxifene or a
      bisphosphonate in 2003 through 2005 and continuous enrollment in the previous 12
      months and subsequent 6 months were identified using a collection of large
      national commercial, Medicare supplemental, and Medicaid administrative claims
      databases (MarketScan). Patients were divided into two cohorts, a combined
      commercial/Medicare cohort and a Medicaid cohort. Within each cohort,
      characteristics (demographic, clinical, and resource utilization) of patients
      initiating raloxifene were compared to those of patients initiating
      bisphosphonate therapy. Group comparisons were made using chi-square tests for
      proportions of categorical measures and Wilcoxon rank-sum tests for continuous
      variables. Logistic regression was used to simultaneously examine factors
      independently associated with initiation of raloxifene versus a bisphosphonate.
      RESULTS: Within both the commercial/Medicare and Medicaid cohorts, raloxifene
      patients were younger, had fewer comorbid conditions, and fewer pre-existing
      fractures than bisphosphonate patients. Raloxifene patients in both cohorts were
      less likely to have had a bone mineral density (BMD) screening in the previous
      year than were bisphosphonate patients, and were also more likely to have used
      estrogen or estrogen/progestin therapy in the previous 12 months. These
      differences remained statistically significant in the multivariate model.
      CONCLUSION: In this sample of patients enrolled in commercial, Medicare, and
      Medicaid plans, patients who initiated raloxifene treatment differed from those
      initiating bisphosphonates. Raloxifene patients were younger, had better overall
      health status and appeared to be less likely to have risk factors for new
      osteoporotic fractures than bisphosphonate patients. Differences in the clinical
      profiles of these agents may impact prescribing decisions. Investigators using
      observational data to make comparisons of treatment outcomes associated with
      these medications should take these important differences in patient
      characteristics into consideration.

PMID- 19105829
TI  - Sequence divergence of Mus spretus and Mus musculus across a skin cancer
      susceptibility locus.
AB  - BACKGROUND: Mus spretus diverged from Mus musculus over one million years ago.
      These mice are genetically and phenotypically divergent. Despite the value of
      utilizing M. musculus and M. spretus for quantitative trait locus (QTL) mapping,
      relatively little genomic information on M. spretus exists, and most of the
      available sequence and polymorphic data is for one strain of M. spretus,
      Spret/Ei. In previous work, we mapped fifteen loci for skin cancer susceptibility
      using four different M. spretus by M. musculus F1 backcrosses. One locus, skin
      tumor susceptibility 5 (Skts5) on chromosome 12, shows strong linkage in one
      cross. RESULTS: To identify potential candidate genes for Skts5, we sequenced 65
      named and unnamed genes and coding elements mapping to the peak linkage area in
      outbred spretus, Spret/EiJ, FVB/NJ, and NIH/Ola. We identified polymorphisms in
      62 of 65 genes including 122 amino acid substitutions. To look for polymorphisms
      consistent with the linkage data, we sequenced exons with amino acid
      polymorphisms in two additional M. spretus strains and one additional M. musculus
      strain generating 40.1 kb of sequence data. Eight candidate variants were
      identified that fit with the linkage data. To determine the degree of variation
      across M. spretus, we conducted phylogenetic analyses. The relatedness of the M.
      spretus strains at this locus is consistent with the proximity of region of
      ascertainment of the ancestral mice. CONCLUSION: Our analyses suggest that, if
      Skts5 on chromosome 12 is representative of other regions in the genome, then
      published genomic data for Spret/EiJ are likely to be of high utility for genomic
      studies in other M. spretus strains.

PMID- 19105830
TI  - Comparative secretome analyses of two Trichoderma reesei RUT-C30 and CL847
      hypersecretory strains.
AB  - BACKGROUND: Due to its capacity to produce large amounts of cellulases,
      Trichoderma reesei is increasingly been researched in various fields of white
      biotechnology, especially in biofuel production from lignocellulosic biomass. The
      commercial enzyme mixtures produced at industrial scales are not well
      characterized, and their proteinaceous components are poorly identified and
      quantified. The development of proteomic methods has made it possible to
      comprehensively overview the enzymes involved in lignocellulosic biomass
      degradation which are secreted under various environmental conditions. RESULTS:
      The protein composition of the secretome produced by industrial T. reesei (strain
      CL847) grown on a medium promoting the production of both cellulases and
      hemicellulases was explored using two-dimensional electrophoresis and MALDI-TOF
      or LC-MS/MS protein identification. A total of 22 protein species were
      identified. As expected, most of them are potentially involved in biomass
      degradation. The 2D map obtained was then used to compare the secretomes produced
      by CL847 and another efficient cellulolytic T. reesei strain, Rut-C30, the
      reference cellulase-overproducing strain using lactose as carbon source and
      inducer of cellulases. CONCLUSION: This study provides the most complete mapping
      of the proteins secreted by T. reesei to date. We report on the first use of
      proteomics to compare secretome composition between two cellulase-overproducing
      strains Rut-C30 and CL847 grown under similar conditions. Comparison of protein
      patterns in both strains highlighted many unexpected differences between
      cellulase cocktails. The results demonstrate that 2D electrophoresis is a
      promising tool for studying cellulase production profiles, whether for industrial
      characterization of an entire secretome or for a more fundamental study on
      cellulase expression at genome-wide scale.

PMID- 19105831
TI  - Diffuse idiopathic skeletal hyperostosis as a cause of progressive dysphagia: a
      case report.
AB  - BACKGROUND: Forestier's disease, also known as diffuse idiopathic skeletal
      hyperostosis (DISH), is an idiopathic rheumatological abnormality in which
      exuberant ossification occurs along throughout the body, but most notably the
      anterior longitudinal ligament of the spine. CASE PRESENTATION: We report on a 75
      year-old white patient with progressive difficulty in swallowing and dysphagia,
      resulting in weight loss over the last two years. Radiological evaluation, (x
      rays and Magnetic resonance imaging), confirmed the diagnosis of DISH, and
      revealed marked compression of the esophagus at the C5-6 level, due to excessive
      ossification of the anterior longitudinal ligament of the cervical spine.The
      patient was treated with anterior cervical approach for removal of the
      hyperostosis without fusion. He had marked improvement in swallowing function and
      was able to resume a normal diet after one month. CONCLUSION: Diffuse idiopathic
      skeletal hyperostosis or Forestier's disease is an uncommon etiology of
      difficulty in swallowing and progressive dysphagia. Surgical excision of the
      cervical osteophytes typically leads to excellent symptomatic results.

PMID- 19105832
TI  - A set of vectors for introduction of antibiotic resistance genes by in vitro Cre
      mediated recombination.
AB  - BACKGROUND: Introduction of new antibiotic resistance genes in the plasmids of
      interest is a frequent task in molecular cloning practice. Classical approaches
      involving digestion with restriction endonucleases and ligation are time
      consuming. FINDINGS: We have created a set of insertion vectors (pINS) carrying
      genes that provide resistance to various antibiotics (puromycin, blasticidin and
      G418) and containing a loxP site. Each vector (pINS-Puro, pINS-Blast or pINS-Neo)
      contains either a chloramphenicol or a kanamycin resistance gene and is unable to
      replicate in most E. coli strains as it contains a conditional R6Kgamma
      replication origin. Introduction of the antibiotic resistance genes into the
      vector of interest is achieved by Cre-mediated recombination between the
      replication-incompetent pINS and a replication-competent target vector. The
      recombination mix is then transformed into E. coli and selected by the resistance
      marker (kanamycin or chloramphenicol) present in pINS, which allows to recover
      the recombinant plasmids with 100% efficiency. CONCLUSION: Here we propose a
      simple strategy that allows to introduce various antibiotic-resistance genes into
      any plasmid containing a replication origin, an ampicillin resistance gene and a
      loxP site.

PMID- 19105833
TI  - The CYP2J2 G-50T polymorphism and myocardial infarction in patients with
      cardiovascular risk profile.
AB  - BACKGROUND: Cytochrome P450 (CYP) enzyme 2J2, an epoxygenase predominantly
      expressed in the heart, metabolizes arachidonic acid to biologically active
      eicosanoids. One of the CYP2J2 products, 11, 12-epoxyeicosatrienoic acid, has
      several vasoprotective effects. The CYP2J2-G-50T-promotor polymorphism decreases
      gene expression and is associated with coronary artery disease. This association
      supports the vascular protective role of CYP-derived eicosanoids in
      cardiovascular disease. In the present study, we investigated the influence of
      this polymorphism on survived myocardial infarction in two study groups of
      patients with on average high cardiovascular risk profile. METHODS: The CYP2J2
      polymorphism was genotyped in two groups of patients that were collected with the
      same method of clinical data collection. Data from 512 patients with sleep apnoea
      (group: OSA) and on average high cardiovascular risk profile and from another 488
      patients who were admitted for coronary angiography (CAR-group) were evaluated
      for a potential correlation of the CYP2J2 polymorphism G-50T and a history of
      myocardial infarction. The G-50T polymorphism of the CYP2J2 gene was genotyped by
      allele specific restriction and light cycler analysis. RESULTS: The T-allele of
      the polymorphism was found in 111 (11.1%; CAR-group: N = 65, 13.3%; OSA: N = 46,
      9.0%). 146 patients had a history of myocardial infarction (CAR: N = 120, 24.6%;
      OSA: N = 26, 5.1%). Cardiovascular risk factors were equally distributed between
      the different genotypes of the CYP2J2 G-50T polymorphism. In the total group of
      1000 individuals, carriers of the T-allele had significantly more myocardial
      infarctions compared to carriers of the wild type (T/T or G/T: 21.6%; G/G: 13.7%;
      p = 0.026, odds ratio 1.73, 95%-CI [1.06-2.83]). In the multivariate logistic
      regression analysis the odds ratio for a history of myocardial infarction in
      carriers of the T-allele was 1.611, 95%-CI [0.957-2.731] but this trend was not
      significant (p = 0.073). CONCLUSION: In presence of other risk factors, the
      CYP2J2 G-50T failed to show a significant role in the development of myocardial
      infarction. However, since our result is close to the border of significance,
      this question should be clarified in larger, prospective studies in the future.

PMID- 19105835
TI  - The meaning of alignment: lessons from structural diversity.
AB  - BACKGROUND: Protein structural alignment provides a fundamental basis for
      deriving principles of functional and evolutionary relationships. It is routinely
      used for structural classification and functional characterization of proteins
      and for the construction of sequence alignment benchmarks. However, the available
      techniques do not fully consider the implications of protein structural diversity
      and typically generate a single alignment between sequences. RESULTS: We have
      taken alternative protein crystal structures and generated simulation snapshots
      to explicitly investigate the impact of structural changes on the alignments. We
      show that structural diversity has a significant effect on structural alignment.
      Moreover, we observe alignment inconsistencies even for modest spatial
      divergence, implying that the biological interpretation of alignments is less
      straightforward than commonly assumed. A salient example is the GroES 'mobile
      loop' where sub-Angstrom variations give rise to contradictory sequence
      alignments. CONCLUSION: A comprehensive treatment of ambiguous alignment regions
      is crucial for further development of structural alignment applications and for
      the representation of alignments in general. For this purpose we have developed
      an on-line database containing our data and new ways of visualizing alignment
      inconsistencies, which can be found at http://www.ibi.vu.nl/databases/stralivari.

PMID- 19105834
TI  - Extensive purifying selection acting on synonymous sites in HIV-1 Group M
      sequences.
AB  - BACKGROUND: Positive selection pressure acting on protein-coding sequences is
      usually inferred when the rate of nonsynonymous substitution is greater than the
      synonymous rate. However, purifying selection acting directly on the nucleotide
      sequence can lower the synonymous substitution rate. This could result in false
      inference of positive selection because when synonymous changes at some sites are
      under purifying selection, the average synonymous rate is an underestimate of the
      neutral rate of evolution. Even though HIV-1 coding sequences contain a number of
      regions that function at the nucleotide level, and are thus likely to be affected
      by purifying selection, studies of positive selection assume that synonymous
      substitutions can be used to estimate the neutral rate of evolution. RESULTS: We
      modelled site-to-site variation in the synonymous substitution rate across coding
      regions of the HIV-1 genome. Synonymous substitution rates were found to vary
      significantly within and between genes. Surprisingly, regions of the genome that
      encode proteins in more than one frame had significantly higher synonymous
      substitution rates than regions coding in a single frame. We found evidence of
      strong purifying selection pressure affecting synonymous mutations in fourteen
      regions with known functions. These included an exonic splicing enhancer, the rev
      responsive element, the poly-purine tract and a transcription factor binding
      site. A further five highly conserved regions were located within known
      functional domains. We also found four conserved regions located in env and vpu
      which have not been characterized previously. CONCLUSION: We provide the
      coordinates of genomic regions with markedly lower synonymous substitution rates,
      which are putatively under the influence of strong purifying selection pressure
      at the nucleotide level as well as regions encoding proteins in more than one
      frame. These regions should be excluded from studies of positive selection acting
      on HIV-1 coding regions.

PMID- 19105836
TI  - A strategy to improve skills in pharmaceutical supply management in East Africa:
      the regional technical resource collaboration for pharmaceutical management.
AB  - BACKGROUND: International initiatives such as the Global Fund to Fight AIDS,
      Tuberculosis and Malaria, the President's Emergency Plan for AIDS Relief and the
      President's Malaria Initiative have significantly increased availability and
      access to medicines in some parts of the developing world. Despite this, however,
      skills remain limited on quantifying needs for medications and ordering,
      receiving and storing medications appropriately; recording medications
      inventories accurately; distributing medications for use appropriately; and
      advising patients on how to use medications appropriately. The Regional Technical
      Resource Collaboration for Pharmaceutical Management (RTRC) has been established
      to help address the problem of skills shortage in pharmaceutical management in
      East Africa. METHODS: The initiative brings together academic institutions from
      four East African countries to participate in skills-building activities in
      pharmaceutical supply management. The initiative targeted the institutions'
      ability to conduct assessments of pharmaceutical supply management systems and to
      develop and implement effective skills-building programmes for pharmaceutical
      supply chain management. RESULTS: Over a two-year period, the RTRC succeeded in
      conducting assessments of pharmaceutical supply management systems and practices
      in Kenya, Rwanda, Tanzania and Uganda. In 2006, the RTRC participated in a
      materials-development workshop in Kampala, Uganda, and contributed to the
      development of comprehensive HIV/AIDS pharmaceutical management training
      materials; these materials are now widely available in all four countries. In
      Tanzania and Uganda the RTRC has been involved with the training of health care
      workers in HIV/AIDS pharmaceutical management. In Kenya, Tanzania and Uganda the
      RTRC has been conducting operations research to find solutions to their
      countries' skills-shortage problems. Some of the interventions tested include
      applying and evaluating the effectiveness of a novel skills-building approach for
      pharmaceutical supply management. CONCLUSION: Nurturing collaboration between
      regional institutions in resource-limited countries to build in-country skills in
      pharmaceutical supply management appears to be an effective intervention. Support
      from local programmes and technical assistance from organizations and
      institutions with the necessary expertise is critical for success, particularly
      at inception. The skills acquired by local institutions can be incorporated into
      both pre-service and in-service teaching curricula. This ensures long-term
      availability of skills in-country. The ability of trained institutions to
      mobilize their own resources for skills-building activities is crucial for the
      success and sustainability of these programmes.

PMID- 19105837
TI  - A modeling study by response surface methodology and artificial neural network on
      culture parameters optimization for thermostable lipase production from a newly
      isolated thermophilic Geobacillus sp. strain ARM.
AB  - BACKGROUND: Thermostable bacterial lipases occupy a place of prominence among
      biocatalysts owing to their novel, multifold applications and resistance to high
      temperature and other operational conditions. The capability of lipases to
      catalyze a variety of novel reactions in both aqueous and nonaqueous media
      presents a fascinating field for research, creating interest to isolate novel
      lipase producers and optimize lipase production. The most important stages in a
      biological process are modeling and optimization to improve a system and increase
      the efficiency of the process without increasing the cost. RESULTS: Different
      production media were tested for lipase production by a newly isolated
      thermophilic Geobacillus sp. strain ARM (DSM 21496 = NCIMB 41583). The maximum
      production was obtained in the presence of peptone and yeast extract as organic
      nitrogen sources, olive oil as carbon source and lipase production inducer,
      sodium and calcium as metal ions, and gum arabic as emulsifier and lipase
      production inducer. The best models for optimization of culture parameters were
      achieved by multilayer full feedforward incremental back propagation network and
      modified response surface model using backward elimination, where the optimum
      condition was: growth temperature (52.3 degrees C), medium volume (50 ml),
      inoculum size (1%), agitation rate (static condition), incubation period (24 h)
      and initial pH (5.8). The experimental lipase activity was 0.47 Uml(-1) at
      optimum condition (4.7-fold increase), which compared well to the maximum
      predicted values by ANN (0.47 Uml(-1)) and RSM (0.476 Uml(-1)), whereas R2 and
      AAD were determined as 0.989 and 0.059% for ANN, and 0.95 and 0.078% for RSM
      respectively. CONCLUSION: Lipase production is the result of a synergistic
      combination of effective parameters interactions. These parameters are in
      equilibrium and the change of one parameter can be compensated by changes of
      other parameters to give the same results. Though both RSM and ANN models
      provided good quality predictions in this study, yet the ANN showed a clear
      superiority over RSM for both data fitting and estimation capabilities. On the
      other hand, ANN has the disadvantage of requiring large amounts of training data
      in comparison with RSM. This problem was solved by using statistical experimental
      design, to reduce the number of experiments.

PMID- 19105838
TI  - Influenza vaccination among healthcare workers in a multidisciplinary University
      hospital in Italy.
AB  - BACKGROUND: Annual influenza vaccination is recommended for healthcare workers
      (HCWs) in order to reduce the morbidity associated with influenza in healthcare
      settings. The aim of this study was to evaluate the current vaccination status of
      the HCWs in one of Italy's largest multidisciplinary University Hospitals.
      METHODS: Between February 1 and March 31, 2006, we carried out a cross-sectional
      study of influenza vaccination coverage among HCWs at the University Hospital
      Fondazione IRCCS "Ospedale Maggiore Policlinico, Mangiagalli e Regina Elena",
      Milan, Italy. After receiving a brief description of the aim of the study, 2,143
      (95%: 1,064 physicians; 855 nurses; 224 paramedics) of 2,240 HCWs self-completed
      an anonymous questionnaire. RESULTS: Influenza vaccination coverage was very low
      in all specialties, varying from 17.6% in the Emergency Department to 24.3% in
      the Surgery Department, and knowledge of influenza epidemiology and prevention
      was poor. The factors positively associated with being vaccinated were an age of
      >or= 45 years, considering influenza a potentially severe disease, and being
      aware of the high-risk categories for which influenza vaccination is strongly
      recommended; those that negatively associated with being vaccinated were being
      female, working in the Medicine Department, and being a nurse or paramedic.
      CONCLUSION: Despite strong recommendations, influenza vaccination coverage seemed
      to be very low among HCWs of all specialties, with differences between areas and
      types of employment. Specific continuous educational and vaccination programs for
      different targets should be urgently organized to reduce morbidity and mortality
      in high-risk patients, contain nosocomial outbreaks, and ensure an appropriate
      socioeconomic impact.

PMID- 19105839
TI  - Comparison of the transcriptomic "stress response" evoked by antimycin A and
      oxygen deprivation in Saccharomyces cerevisiae.
AB  - BACKGROUND: Acute changes in environmental parameters (e.g., O2, pH, UV,
      osmolarity, nutrients, etc.) evoke a common transcriptomic response in yeast
      referred to as the "environmental stress response" (ESR) or "common environmental
      response" (CER). Why such a diverse array of insults should elicit a common
      transcriptional response remains enigmatic. Previous functional analyses of the
      networks involved have found that, in addition to up-regulating those for
      mitigating the specific stressor, the majority appear to be involved in balancing
      energetic supply and demand and modulating progression through the cell cycle.
      Here we compared functional and regulatory aspects of the stress responses
      elicited by the acute inhibition of respiration with antimycin A and oxygen
      deprivation under catabolite non-repressed (galactose) conditions. RESULTS: Gene
      network analyses of the transcriptomic responses revealed both treatments result
      in the transient (10 - 60 min) down-regulation of MBF- and SBF-regulated networks
      involved in the G1/S transition of the cell cycle as well as Fhl1 and PAC/RRPE
      associated networks involved in energetically costly programs of ribosomal
      biogenesis and protein synthesis. Simultaneously, Msn2/4 networks involved in
      hexose import/dissimilation, reserve energy regulation, and autophagy were
      transiently up-regulated. Interestingly, when cells were treated with antimycin A
      well before experiencing anaerobiosis these networks subsequently failed to
      respond to oxygen deprivation. These results suggest the transient stress
      response is elicited by the acute inhibition of respiration and, we postulate,
      changes in cellular energetics and/or the instantaneous growth rate, not oxygen
      deprivation per se. After a considerable delay (> or = 1 generation) under
      anoxia, predictable changes in heme-regulated gene networks (e.g., Hap1,
      Hap2/3/4/5, Mot3, Rox1 and Upc2) were observed both in the presence and absence
      of antimycin A. CONCLUSION: This study not only differentiates between the gene
      networks that respond to respiratory inhibition and those that respond to oxygen
      deprivation but suggests the function of the ESR or CER is to balance energetic
      supply/demand and coordinate growth with the cell cycle, whether in response to
      perturbations that disrupt catabolic pathways or those that require rapidly up
      regulating energetically costly programs for combating specific stressors.

PMID- 19105840
TI  - Smoking, dementia and cognitive decline in the elderly, a systematic review.
AB  - BACKGROUND: Nicotine may aid reaction time, learning and memory, but smoking
      increases cardiovascular risk. Cardiovascular risk factors have been linked to
      increased risk of dementia. A previous meta-analysis found that current smokers
      were at higher risk of subsequent dementia, Alzheimer's disease, vascular
      dementia and cognitive decline. METHODS: In order to update and examine this
      further a systematic review and meta-analysis was carried out using different
      search and inclusion criteria, database selection and more recent publications.
      Both reviews were restricted to those aged 65 and over. RESULTS: The review
      reported here found a significantly increased risk of Alzheimer's disease with
      current smoking and a likely but not significantly increased risk of vascular
      dementia, dementia unspecified and cognitive decline. Neither review found clear
      relationships with former smoking. CONCLUSION: Current smoking increases risk of
      Alzheimer's disease and may increase risk of other dementias. This reinforces
      need for smoking cessation, particularly aged 65 and over. Nicotine alone needs
      further investigation.

PMID- 19105841
TI  - Limited Wegener's granulomatosis presenting as lung nodules in a patient with
      rheumatoid arthritis: a case report.
AB  - BACKGROUND: Rheumatoid arthritis has varied pleuroparenchymal manifestations.
      Wegener's granulomatosis can develop in an established case of rheumatoid
      arthritis and this association although previously reported is very rare. CASE
      PRESENTATION: A 60-year-old lady had been diagnosed with rheumatoid arthritis on
      the basis of her clinical symptoms and serological tests which were positive RA
      factor and anti-CCP antibodies. Her rheumatoid arthritis activity had been mild
      and well controlled with hydroxychloroquine and low dose prednisone. She
      presented with a productive cough and right-sided pleuritic chest pain. CT scan
      of the chest showed three lung nodules with increased uptake on PET CT scan,
      raising concerns for an inflammatory or malignant process. The differential
      diagnosis included rheumatoid nodules, infections or malignancy. A CT-guided
      needle biopsy of the largest nodule was undertaken which showed vasculitis
      typical of Wegener's granulomatosis. Stains and cultures of the biopsy specimen
      were negative for bacteria, fungi and acid fast bacilli. A panel of serological
      tests for vasculitis were checked and showed elevated titers of cANCA and anti
      proteinase 3 antibodies. Urine analysis and CT scan of paranasal sinuses was
      normal. Since the upper respiratory tract and the kidneys were spared a diagnosis
      of limited Wegener's granulomatosis affecting only the lungs was made. Due to the
      toxicity of cyclophosphamide, her relatively mild disease sparing the kidneys and
      the underlying rheumatoid arthritis, weekly methotrexate was started and low dose
      prednisone was continued. She had marked symptomatic improvement and complete
      resolution of the nodules was documented on subsequent imaging. CONCLUSION:
      Wegener's granulomatosis developing in a patient with rheumatoid arthritis is
      very rare but should be considered as it warrants a different and possibly more
      aggressive treatment approach.

PMID- 19105842
TI  - Aripiprazole augmentation in poor insight obsessive-compulsive disorder: a case
      report.
AB  - BACKGROUND: Obsessive-compulsive disorder is associated with a relevant
      impairment in social and interpersonal functioning and severe disability. This
      seems to be particularly true for the poor insight subtype, characterised by a
      lack of consciousness of illness and, consequently, compliance with treatment.
      Poor responsiveness to serotonergic drugs in poor insight obsessive-compulsive
      patients may also require an augmentation therapy with atypical antipsychotics.
      METHODS: We reviewed a case in which a patient with a long history of poor
      insight obsessive-compulsive disorder was treated with a high dosage of serotonin
      reuptake inhibitors. RESULTS: The treatment resulted in a poor outcome. This
      patient was therefore augmentated with aripiprazole. CONCLUSION: Doctors should
      consider aripiprazole as a possible augmentation strategy for serotonergic poor
      responder obsessive-compulsive patients, but further research on these subjects
      is needed.

PMID- 19105843
TI  - INSIG2 gene polymorphism is associated with increased subcutaneous fat in women
      and poor response to resistance training in men.
AB  - BACKGROUND: A common SNP upstream of the INSIG2 gene, rs7566605 (g.-10,1025G>C,
      Chr2:118,552,255, NT_022135.15), was reported to be associated with obesity (Body
      Mass Index, [BMI]) in a genome-wide association scan using the Framingham Heart
      Study but has not been reproduced in other cohorts. As BMI is a relatively
      insensitive measure of adiposity that is subject to many confounding variables,
      we sought to determine the relationship between the INSIG2 SNP and subcutaneous
      fat volumes measured by MRI in a young adult population. METHODS: We genotyped
      the INSIG2 SNP rs7566605 in college-aged population enrolled in a controlled
      resistance-training program, (the Functional Polymorphism Associated with Human
      Muscle Size and Strength, FAMuSS cohort, n = 752 volunteers 18-40 yrs). In this
      longitudinal study, we examined the effect of the INSIG2 polymorphism on
      subcutaneous fat and muscle volumes of the upper arm measured by magnetic
      resonance imaging (MRI) before and after 12 wks of resistance training.
      Gene/phenotype associations were tested using an analysis of covariance model
      with age and weight as covariates. Further, the % variation in each phenotype
      attributable to genotype was determined using hierarchical models and tested with
      a likelihood ratio test. RESULTS: Women with a copy of the C allele had higher
      levels of baseline subcutaneous fat (GG: n = 139; 243473 +/- 5713 mm3 vs. GC/CC:
      n = 181; 268521 +/- 5003 mm3; p = 0.0011); but men did not show any such
      association. Men homozygous for the G ancestral allele showed a loss of
      subcutaneous fat, while those with one or two copies of the C allele gained a
      greater percentage of subcutaneous fat with resistance training (GG: n = 103;
      1.02% +/- 1.74% vs. GC/CC: n = 93; 6.39% +/- 1.82%; p = 0.035). CONCLUSION: Our
      results show that the INSIG2 rs7566605 polymorphism underlies variation in
      subcutaneous adiposity in young adult women and suppresses the positive effects
      of resistance training on men. This supports and extends the original finding
      that there is an association between measures of obesity and INSIG2 rs7566605 and
      further implicates this polymorphism in fat regulation.

PMID- 19105844
TI  - Uncoupling GP1 and GP2 expression in the Lassa virus glycoprotein complex:
      implications for GP1 ectodomain shedding.
AB  - BACKGROUND: Sera from convalescent Lassa fever patients often contains antibodies
      to Lassa virus (LASV) glycoprotein 1 (GP1), and glycoprotein 2 (GP2);
      Immunization of non-human primates with viral vectors expressing the arenaviral
      glycoprotein complex (GPC) confers full protective immunity against a lethal
      challenge with LASV. Thus, the development of native or quasi native recombinant
      LASV GP1 and GP2 as soluble, uncoupled proteins will improve current diagnostics,
      treatment, and prevention of Lassa fever. To this end, mammalian expression
      systems were engineered for production and purification of secreted forms of
      soluble LASV GP1 and GP2 proteins. RESULTS: Determinants for mammalian cell
      expression of secreted uncoupled Lassa virus (LASV) glycoprotein 1 (GP1) and
      glycoprotein 2 (GP2) were established. Soluble GP1 was generated using either the
      native glycoprotein precursor (GPC) signal peptide (SP) or human IgG signal
      sequences (s.s.). GP2 was secreted from cells only when (1) the transmembrane
      (TM) domain was deleted, the intracellular domain (IC) was fused to the
      ectodomain, and the gene was co-expressed with a complete GP1 gene in cis; (2)
      the TM and IC domains were deleted and GP1 was co-expressed in cis; (3)
      expression of GP1 was driven by the native GPC SP. These data implicate GP1 as a
      chaperone for processing and shuttling GP2 to the cell surface. The soluble forms
      of GP1 and GP2 generated through these studies were secreted as homogeneously
      glycosylated proteins that contained high mannose glycans. Furthermore,
      observation of GP1 ectodomain shedding from cells expressing wild type LASV GPC
      represents a novel aspect of arenaviral glycoprotein expression. CONCLUSION:
      These results implicate GP1 as a chaperone for the correct processing and
      shuttling of GP2 to the cell surface, and suggest that native GPC SP plays a role
      in this process. In the absence of GP1 and GPC SP the GP2 protein may be
      processed by an alternate pathway that produces heterogeneously glycosylated
      protein, or the polypeptide may not fully mature in the secretory cascade in
      mammalian cells. The expression constructs developed in these studies resulted in
      the generation and purification of soluble, uncoupled GP1 and GP2 proteins from
      mammalian cells with quasi-native properties. The observation of GP1 ectodomain
      shedding from cells expressing wild type LASV GPC establishes new correlates of
      disease progression and highlights potential opportunities for development of
      diagnostics targeting the early stages of Lassa fever.

PMID- 19105845
TI  - Effect of increasing intraperitoneal infusion rates on bupropion hydrochloride
      induced seizures in mice.
AB  - BACKGROUND: It is not known if there is a relationship between input rate and
      incidence of bupropion-induced seizures. This is important, since different
      controlled release formulations of bupropion release the active drug at different
      rates. METHODS: We investigated the effect of varying the intraperitoneal
      infusion rates of bupropion HCl 120 mg/kg, a known convulsive dose 50 (CD50), on
      the incidence and severity of bupropion-induced convulsions in the Swiss albino
      mice. A total of 69 mice, approximately 7 weeks of age, and weighing 21.0 to 29.1
      g were randomly assigned to bupropion HCl 120 mg/kg treatment by intraperitoneal
      (IP) administration in 7 groups (9 to 10 animals per group). Bupropion HCl was
      infused through a surgically implanted IP dosing catheter with infusions in each
      group of 0 min, 15 min, 30 min, 60 min, 90 min, 120 min, and 240 min. The number,
      time of onset, duration and the intensity of the convulsions or absence of
      convulsions were recorded. RESULTS: The results showed that IP administration of
      bupropion HCl 120 mg/kg by bolus injection induced convulsions in 6 out of 10
      mice (60% of convulsing mice) in group 1. Logistic regression analysis revealed
      that infusion time was significant (p = 0.0004; odds ratio = 0.974) and
      increasing the IP infusion time of bupropion HCl 120 mg/kg was associated with a
      91% reduced odds of convulsions at infusion times of 15 to 90 min compared to
      bolus injection. Further increase in infusion time resulted in further reduction
      in the odds of convulsions to 99.8% reduction at 240 min. CONCLUSION: In
      conclusion, the demonstration of an inverse relationship between infusion time of
      a fixed and convulsive dose of bupropion and the risk of convulsions in a
      prospective study is novel.

PMID- 19105846
TI  - A systematic approach to biomarker discovery; preamble to "the iSBTc-FDA
      taskforce on immunotherapy biomarkers".
AB  - The International Society for the Biological Therapy of Cancer (iSBTc) has
      initiated in collaboration with the United States Food and Drug Administration
      (FDA) a programmatic look at innovative avenues for the identification of
      relevant parameters to assist clinical and basic scientists who study the natural
      course of host/tumor interactions or their response to immune manipulation. The
      task force has two primary goals: 1) identify best practices of standardized and
      validated immune monitoring procedures and assays to promote inter-trial
      comparisons and 2) develop strategies for the identification of novel biomarkers
      that may enhance our understating of principles governing human cancer immune
      biology and, consequently, implement their clinical application. Two working
      groups were created that will report the developed best practices at an
      NCI/FDA/iSBTc sponsored workshop tied to the annual meeting of the iSBTc to be
      held in Washington DC in the Fall of 2009. This foreword provides an overview of
      the task force and invites feedback from readers that might be incorporated in
      the discussions and in the final document.

PMID- 19105847
TI  - Prostate cancer--to screen, or not to screen, is that the question?
AB  - There continues to be controversy regarding serum Prostate-Specific Antigen (PSA)
      and prostate cancer screening. We anxiously await the results of two large
      prospective randomized clinical trials (Prostate, Lung, Colon, and Ovary-PCLO
      screening trial in the US and European Randomized Study of Screening for Prostate
      Cancer-ERSPC in Europe) assessing the benefits of prostate cancer screening.
      However the true question to answer may be which cancer to treat and when should
      we treat it.

PMID- 19105848
TI  - Human and mouse switch-like genes share common transcriptional regulatory
      mechanisms for bimodality.
AB  - BACKGROUND: Gene expression is controlled over a wide range at the transcript
      level through complex interplay between DNA and regulatory proteins, resulting in
      profiles of gene expression that can be represented as normal, graded, and
      bimodal (switch-like) distributions. We have previously performed genome-scale
      identification and annotation of genes with switch-like expression at the
      transcript level in mouse, using large microarray datasets for healthy tissue, in
      order to study the cellular pathways and regulatory mechanisms involving this
      class of genes. We showed that a large population of bimodal mouse genes encoding
      for cell membrane and extracellular matrix proteins is involved in communication
      pathways. This study expands on previous results by annotating human bimodal
      genes, investigating their correspondence to bimodality in mouse orthologs and
      exploring possible regulatory mechanisms that contribute to bimodality in gene
      expression in human and mouse. RESULTS: Fourteen percent of the human genes on
      the HGU133A array (1847 out of 13076) were identified as bimodal or switch-like.
      More than 40% were found to have bimodal mouse orthologs. KEGG pathways enriched
      for bimodal genes included ECM-receptor interaction, focal adhesion, and tight
      junction, showing strong similarity to the results obtained in mouse. Tissue
      specific modes of expression of bimodal genes among brain, heart, and skeletal
      muscle were common between human and mouse. Promoter analysis revealed a higher
      than average number of transcription start sites per gene within the set of
      bimodal genes. Moreover, the bimodal gene set had differentially methylated
      histones compared to the set of the remaining genes in the genome. CONCLUSION:
      The fact that bimodal genes were enriched within the cell membrane and
      extracellular environment make these genes as candidates for biomarkers for
      tissue specificity. The commonality of the important roles bimodal genes play in
      tissue differentiation in both the human and mouse indicates the potential value
      of mouse data in providing context for human tissue studies. The regulation
      motifs enriched in the bimodal gene set (TATA boxes, alternative promoters,
      methlyation) have known associations with complex diseases, such as cancer,
      providing further potential for the use of bimodal genes in studying the
      molecular basis of disease.

PMID- 19105849
TI  - The inhibition of assembly of HIV-1 virus-like particles by 3-O-(3',3'
      dimethylsuccinyl) betulinic acid (DSB) is counteracted by Vif and requires its
      Zinc-binding domain.
AB  - BACKGROUND: DSB, the 3-O-(3',3'dimethylsuccinyl) derivative of betulinic acid,
      blocks the last step of protease-mediated processing of HIV-1 Gag precursor
      (Pr55Gag), which leads to immature, noninfectious virions. When administered to
      Pr55Gag-expressing insect cells (Sf9), DSB inhibits the assembly and budding of
      membrane-enveloped virus-like particles (VLP). In order to explore the
      possibility that viral factors could modulate the susceptibility to DSB of the
      VLP assembly process, several viral proteins were coexpressed individually with
      Pr55Gag in DSB-treated cells, and VLP yields assayed in the extracellular medium.
      RESULTS: Wild-type Vif (Vifwt) restored the VLP production in DSB-treated cells
      to levels observed in control, untreated cells. DSB-counteracting effect was also
      observed with Vif mutants defective in encapsidation into VLP, suggesting that
      packaging and anti-DSB effect were separate functions in Vif. The anti-DSB effect
      was abolished for VifC133S and VifS116V, two mutants which lacked the zinc
      binding domain (ZBD) formed by the four H(108)C(114)C(133)H(139) coordinates with
      a Zn atom. Electron microscopic analysis of cells coexpressing Pr55Gag and Vifwt
      showed that a large proportion of VLP budded into cytoplasmic vesicles and were
      released from Sf9 cells by exocytosis. However, in the presence of mutant
      VifC133S or VifS116V, most of the VLP assembled and budded at the plasma
      membrane, as in control cells expressing Pr55Gag alone. CONCLUSION: The function
      of HIV-1 Vif protein which negated the DSB inhibition of VLP assembly was
      independent of its packaging capability, but depended on the integrity of ZBD. In
      the presence of Vifwt, but not with ZBD mutants VifC133S and VifS116V, VLP were
      redirected to a vesicular compartment and egressed via the exocytic pathway.

PMID- 19105850
TI  - Essential operating principles for tumor spheroid growth.
AB  - BACKGROUND: Our objective was to discover in silico axioms that are plausible
      representations of the operating principles realized during characteristic growth
      of EMT6/Ro mouse mammary tumor spheroids in culture. To reach that objective we
      engineered and iteratively falsified an agent-based analogue of EMT6 spheroid
      growth. EMT6 spheroids display consistent and predictable growth characteristics,
      implying that individual cell behaviors are tightly controlled and regulated. An
      approach to understanding how individual cell behaviors contribute to system
      behaviors is to discover a set of principles that enable abstract agents to
      exhibit closely analogous behaviors using only information available in an
      agent's immediate environment. We listed key attributes of EMT6 spheroid growth,
      which became our behavioral targets. Included were the development of a necrotic
      core surrounded by quiescent and proliferating cells, and growth data at two
      distinct levels of nutrient. RESULTS: We then created an analogue made up of
      quasi-autonomous software agents and an abstract environment in which they could
      operate. The system was designed so that upon execution it could mimic EMT6 cells
      forming spheroids in culture. Each agent used an identical set of axiomatic
      operating principles. In sequence, we used the list of targeted attributes to
      falsify and revise these axioms, until the analogue exhibited behaviors and
      attributes that were within prespecified ranges of those targeted, thereby
      achieving a level of validation. CONCLUSION: The finalized analogue required nine
      axioms. We posit that the validated analogue's operating principles are
      reasonable representations of those utilized by EMT6/Ro cells during tumor
      spheroid development.

PMID- 19105851
TI  - Plasma gelsolin as a biomarker of inflammation.
AB  - The prognostic implications of declining plasma gelsolin levels have been
      documented after a diverse variety of acute insults. Because gelsolin
      concentrations fall prior to the development of complications, a
      pathophysiological role for gelsolin depletion has been postulated in delayed
      multiorgan failure. The original hypothesis about the function of circulating
      gelsolin was that it scavenged actin released from cells at the site of injury.
      Although extracellular actin may be the primary cause of gelsolin depletion, the
      biologic imperative for gelsolin could entail the modulation of several
      inflammatory mediators as much as the disposal of actin. Translational research
      is actively addressing whether replenishment of plasma gelsolin could provide an
      efficacious and well tolerated therapeutic intervention in selected seriously ill
      patients.

PMID- 19105852
TI  - School meals in French secondary state schools with regard to the national
      recommendations.
AB  - In 2001, a circular addressing both the composition of school meals and food
      safety issues was introduced in France to improve the nutrient composition of
      school meals and provided food-frequency guidelines to guarantee dietary balanced
      meals. The present study assesses the extent to which secondary state schools are
      familiar with and implement this circular. In 2005, a nationally representative
      sample of 1440 secondary state schools received a questionnaire on their catering
      service and the implementation of the circular's recommendations, and were
      requested to enclose all menus (lunches and dinners) served over 1 month. Menu
      analysis shows that progress is still required to achieve a meal composition in
      accordance with the food-group frequency guidelines appended to the circular.
      Some recommendations are followed by most of the schools, such as limiting high
      fat products and providing plenty of raw fruits and vegetables, cooked vegetables
      and starchy foods. Other guidelines should be implemented further, especially
      with regard to the nutritional quality of main courses and dairy products, which
      are met by less than a third and a half of schools, respectively. Specific
      efforts are necessary for evening meals to ensure that the nutritional
      requirements of boarders are covered. Some recommendations, such as the food
      purchasing manager being trained in nutrition (38 % of schools) and the
      involvement of dietetic expertise when designing meals (6 %), seem to be linked
      to better dietary balance of meals. Implementation of the circular must therefore
      be promoted in schools and may require stronger regulatory nutrition standards
      and better cooperation between schools.

PMID- 19105853
TI  - Plasma phospholipid fatty acids and CHD in older men: Whitehall study of London
      civil servants.
AB  - Dietary fatty acids (FA) are the major determinants of blood lipids, and
      measurements of plasma phospholipid FA (PL-FA) composition that reflect the
      dietary intake of FA may provide insights into the relationships between diet and
      CHD. We assessed CHD mortality associations with PL-FA (SFA, PUFA and MUFA)
      levels measured in a nested case-control study of 116 cases of CHD death and 239
      controls that were frequency-matched for age and employment grade. The
      participants had plasma levels of total cholesterol, LDL-cholesterol (LDL-C), HDL
      cholesterol, apo B and apo A1, C-reactive protein (CRP) and fibrinogen recorded.
      SFA levels were significantly positively correlated with total cholesterol, LDL
      C, apo B, CRP protein and fibrinogen. By contrast, phospholipid-PUFA were
      inversely associated with CRP, but not with any of the lipids. A higher SFA
      content (top v. bottom quarter) was associated with a 2-fold higher risk of CHD
      (OR and 95 % CI: OR 2.12; 95 % CI: 1.13, 3.99), and an equivalent difference in
      PUFA was associated with a halving in CHD risk (OR 0.49; 95 % CI: 0.26, 0.94),
      but MUFA was unrelated to CHD risk. These associations were substantially
      attenuated, after additional adjustment for lipids and inflammatory markers.
      Higher levels of saturated fat and lower levels of polyunsaturated fats were each
      associated with a higher risk of CHD in elderly men, and these associations were
      partly explained by their effects on blood lipids and biomarkers of inflammation.

PMID- 19105854
TI  - Effect of beta-carotene-rich tomato lycopene beta-cyclase ( tlcy-b) on cell
      growth inhibition in HT-29 colon adenocarcinoma cells.
AB  - Lycopene beta-cyclase (tlcy-b) tomatoes, obtained by modulating carotenogenesis
      via genetic engineering, contain a large amount of beta-carotene, as clearly
      visible by their intense orange colour. In the present study we have subjected
      tlcy-b tomatoes to an in vitro simulated digestion and analysed the effects of
      digestate on cell proliferation. To this aim we used HT-29 human colon
      adenocarcinoma cells, grown in monolayers, as a model. Digested tomatoes were
      diluted (20 ml, 50 ml and 100 ml/l) in culture medium and added to the cells for
      different incubation times (24 h, 48 h and 72 h). Inhibition of cell growth by
      tomato digestate was dose-dependent and resulted from an arrest of cell cycle
      progression at the G0/G1 and G2/M phase and by apoptosis induction. A down
      regulation of cyclin D1, Bcl-2 and Bcl-xl expression was observed. We also found
      that heat treatment of samples before digestion enhanced beta-carotene release
      and therefore cell growth inhibition. To induce with purified beta-carotene
      solubilised in tetrahydrofuran the same cell growth inhibition obtained with the
      tomato digestate, a higher amount of the carotenoid was necessary, suggesting
      that beta-carotene micellarised during digestion is utilised more efficiently by
      the cells, but also that other tomato molecules, reasonably made available during
      digestion, may be present and cooperate with beta-carotene in promoting cell
      growth arrest.

PMID- 19105855
TI  - fMRI changes over time and reproducibility in unmedicated subjects at high
      genetic risk of schizophrenia.
AB  - BACKGROUND: Functional brain abnormalities have been repeatedly demonstrated in
      schizophrenia but there is little data concerning their progression. For such
      studies to have credibility it is first important to establish the
      reproducibility of functional imaging techniques. The current study aimed to
      examine these factors in healthy controls and in unmedicated subjects at high
      genetic risk of the disorder: (i) to examine the reproducibility of task-related
      activation patterns, (ii) to determine if there were any progressive functional
      changes in high-risk subjects versus controls reflecting inheritance of the
      schizophrenic trait, and (iii) to examine changes over time in relation to
      fluctuating positive psychotic symptoms (i.e. state effects). METHOD: Subjects
      were scanned performing the Hayling sentence completion test on two occasions 18
      months apart. Changes in activation were examined in controls and high-risk
      subjects (n=16, n=63). Reproducibility was assessed for controls and high-risk
      subjects who remained asymptomatic at both time points (n=16, n=32). RESULTS:
      Intra-class correlation values indicated good agreement between scanning
      sessions. No significant differences over time were seen between the high-risk
      and control group; however, comparison of high-risk subjects who developed
      symptoms versus those who remained asymptomatic revealed activation increases in
      the left middle temporal gyrus (p=0.026). CONCLUSIONS: The current results
      suggest that functional changes over time occur in the lateral temporal cortex as
      high genetic risk subjects become symptomatic, further, they indicate the
      usefulness of functional imaging tools for investigating progressive changes
      associated with state and trait effects in schizophrenia.

PMID- 19105856
TI  - Set shifting and reversal learning in patients with bipolar disorder or
      schizophrenia.
AB  - BACKGROUND: Bipolar disorder and schizophrenia have both been associated with
      deficits in extra-dimensional set shifting (EDS). Deficits in reversal learning
      (RL) have also been shown in schizophrenia but not in bipolar disorder. This
      study sought to assess the specificity of these findings in a direct comparison
      of clinically stable patients with each disorder. METHOD: The intra
      dimensional/extra-dimensional (IDED) set-shifting task, part of the Cambridge
      Neuropsychological Test Automated Battery (CANTAB), was administered to 30
      patients with schizophrenia, 47 with bipolar disorder and a group of 44
      unaffected controls. EDS and RL errors were compared between the groups and
      related to measures of current and past psychiatric symptoms and medication.
      RESULTS: Both groups of patients with schizophrenia or bipolar disorder made more
      EDS and RL errors than controls. Neither measure separated the two disorders,
      even when the analysis was restricted to euthymic patients. No relationship was
      found with prescribed medication. CONCLUSIONS: Patients with bipolar disorder or
      schizophrenia show common deficits in EDS and RL. These deficits do not seem to
      be attributable to current symptoms and are consistent with disrupted networks
      involving the ventral prefrontal cortex.

PMID- 19105857
TI  - Is adult attention deficit hyperactivity disorder a valid diagnosis in the
      presence of high IQ?
AB  - BACKGROUND: Because the diagnosis of attention deficit hyperactivity disorder
      (ADHD) in higher education settings is rapidly becoming a contentious issue,
      particularly among patients with high IQs, we sought to assess the validity of
      diagnosing ADHD in high-IQ adults and to further characterize the clinical
      features associated with their ADHD. METHOD: We operationalized high IQ as having
      a full-scale IQ120. We identified 53 adults with a high IQ who did not have ADHD
      and 64 adults with a high IQ who met diagnostic criteria for ADHD. Groups did not
      differ on IQ, socio-economic status or gender. RESULTS: High-IQ adults with ADHD
      reported a lower quality of life, had poorer familial and occupational
      functioning, and had more functional impairments, including more speeding
      tickets, accidents and arrests. Major depressive disorder, obsessive-compulsive
      disorder and generalized anxiety disorder diagnoses were higher in high-IQ adults
      with ADHD. All other psychiatric co-morbidities, including antisocial personality
      disorder and substance abuse, did not differ between the two high-IQ groups. ADHD
      was more prevalent in first-degree relatives of adults with ADHD relative to
      controls. CONCLUSIONS: Our data suggest that adults with ADHD and a high IQ
      display patterns of functional impairments, familiality and psychiatric co
      morbidities that parallel those found in the average-IQ adult ADHD population.

PMID- 19105858
TI  - From sound to syntax: phonological constraints on children's lexical
      categorization of new words.
AB  - Two studies examined the role of phonological cues in the lexical categorization
      of new words when children could also rely on learning by exclusion and whether
      the role of phonology depends on extensive experience with a language.
      Phonological cues were assessed via phonological typicality - an aggregate
      measure of the relationship between the phonology of a word and the phonology of
      words in the same lexical class. Experiment 1 showed that when monolingual
      English-speaking seven-year-olds could rely on learning by exclusion,
      phonological typicality only affected their initial inferences about the words.
      Consistent with recent computational analyses, phonological cues had stronger
      impact on the processing of verb-like than noun-like items. Experiment 2 revealed
      an impact of French on the performance of seven-year-olds in French immersion
      when tested in a French language environment. Thus, phonological knowledge may
      affect lexical categorization even in the absence of extensive experience.

PMID- 19105859
TI  - Factors associated with a positive intake of folic acid in the periconceptional
      period among Korean women.
AB  - OBJECTIVE: We aimed to investigate the factors associated with a positive intake
      of folic acid (FA) during the periconceptional period among Korean women. DESIGN:
      In a cross-sectional study of demographic, obstetric and socio-economic data,
      history of periconceptional intake of FA and awareness of the benefits of FA
      supplementation in pregnancy were obtained and analysed using the chi2 test,
      followed by multiple logistic regression analysis. SETTING: The Maternity School,
      Cheil General Hospital and Women's Healthcare Center, Seoul, South Korea, between
      October 2005 and March 2006. SUBJECTS: In total 1313 pregnant women participating
      in a two-day training course available every month. RESULTS: After excluding
      subjects with incomplete or inconsistent data, there were 1277 women included in
      the analysis. Participants were aged 29.4 (sd 2.9) years and had a mean
      gestational age of 27.9 (sd 7.1) weeks. Only 131 (10.3 %) women took FA during
      the periconceptional period. According to multiple logistic regression analyses,
      the adjusted OR for FA supplementation was 1.79 (95 % CI 1.10, 2.91) in women who
      had previous spontaneous abortions, 4.10 (95 % CI 2.43, 6.78) in women who
      planned their pregnancy and 6.63 (95 % CI 2.08, 21.12) in those who were aware of
      the protective effects of FA. CONCLUSIONS: Periconceptional intake of FA was more
      likely among Korean women with a history of previous spontaneous abortion, who
      planned their pregnancy or who were aware of the protective effects of FA during
      pregnancy. However, the proportion of women who took FA in the periconceptional
      period was low.

PMID- 19105860
TI  - Iodine status in a Sherpa community in a village of the Khumbu region of Nepal.
AB  - OBJECTIVE: To assess the iodine status of Sherpa residents living in Kunde
      village, Khumbu region, Nepal. DESIGN: Prevalence of goitre was determined by
      palpation. Urinary iodine concentrations (UIC) were determined in casual morning
      samples, and thyroid-stimulating hormone (TSH) in finger-prick blood samples on
      filter paper. Dietary and demographic data were obtained via questionnaire, and
      selected foods analysed for iodine. SETTING: Khumbu region is an area of low soil
      iodine in Nepal, where the prevalence of goitre was greater than 90% in the 1960s
      prior to iodine intervention. SUBJECTS: Two hundred and fifteen of 219 permanent
      residents of Kunde were studied. RESULTS: Overall prevalence of goitre was 31%
      (Grade 1 goitre, 27.0%; Grade 2, 4.2%). When adjusted to a world population,
      goitre prevalence was 27% (95% CI 23, 32%); Grade 2 goitre prevalence was 2.8%
      (95% CI 1.0, 4.6%). Median UIC was 97 microg/l, but only 75 microg/l in women of
      childbearing age. Thirty per cent had UIC < 50 microg/l and 52% had UIC < 100
      microg/l, while 31% of children aged <14 years had UIC > 300 microg/l. Ten per
      cent of participants had TSH concentrations >5 microU/ml. CONCLUSIONS: The
      prevalence of severe iodine deficiency has decreased since the 1960s, but mild
      iodine deficiency persists, particularly in women of childbearing age. The
      consumption of high-iodine uncooked instant noodles and flavour sachets by school
      aged children contributed to their low prevalence of goitre and excessive UIC
      values. This finding may obscure a more severe iodine deficiency in the
      population, while increasing the risk of iodine-induced hyperthyroidism in
      children. Ongoing monitoring is essential.

PMID- 19105861
TI  - Perceived access to fruits and vegetables associated with increased consumption.
AB  - OBJECTIVE: To examine the association between fruit and vegetable access in the
      community and change in fruit and vegetable consumption among participants in
      community-based health promotion programmes. DESIGN: Fruit and vegetable
      consumption and perceived access to fresh fruit and vegetables were measured by
      self-administered questionnaires at programme start, end and 1-year follow-up.
      Community produce availability was determined by grocery store assessments
      measuring the display space devoted to fruit and vegetable offerings, as well as
      price, variety and freshness. A total of nine communities were studied; 130
      participants completed the fruit and vegetable portions of the questionnaires and
      could be linked to grocery store assessments. RESULTS: Participants made modest
      but significant increases in fruit and vegetable consumption from programme start
      to end: the average increase was 2.88 (95% CI 1.52, 4.25) servings weekly; the
      average increase from start to follow-up was 2.52 (95% CI 1.09, 3.95) servings
      weekly. Greater perceived access to fruits and vegetables was significantly
      associated with higher increases in fruit and vegetable consumption from
      programme start to programme end. Greater availability of produce was associated
      with greater increases in fruit and vegetable servings from programme start to
      programme end as measured by store assessments. CONCLUSIONS: Environmental
      factors, such as access to fruits and vegetables, can modify the effects of
      community interventions. Interventions with the goal of increasing fruit and
      vegetable consumption should consider focusing on increasing access to fresh
      fruits and vegetables in target communities. Similarly, researchers may want to
      study access as an intervention, not just a contextual variable.

PMID- 19105862
TI  - Do dietary patterns in older men influence change in homocysteine through folate
      fortification? The Normative Aging Study.
AB  - OBJECTIVE: We aimed to describe the difference in B-vitamin intake and in plasma
      B-vitamin and homocysteine concentrations before and after folic acid
      fortification, in relation to dietary patterns. DESIGN: The Normative Aging Study
      (NAS) is a longitudinal study on ageing. Between 1961 and 1970, 2280 male
      volunteers aged 21-80 years (mean 42 years) were recruited. Dietary intake data
      have been collected since 1987 and assessment of plasma B vitamins and
      homocysteine was added in 1993. SETTING: Boston, Massachusetts, USA. SUBJECTS: In
      the present study, 354 men who had completed at least one FFQ and one measurement
      of homocysteine, both before and after the fortification period, were included.
      RESULTS: Three dietary patterns were identified by cluster analysis: (i) a
      prudent pattern, with relatively high intakes of fruit, vegetables, low-fat milk
      and breakfast cereals; (ii) an unhealthy pattern, with high intakes of baked
      products, sweets and added fats; and (iii) a low fruit and vegetable but
      relatively high alcohol intake pattern. Dietary intake and plasma concentrations
      of folate increased significantly (P < 0.05) among all dietary patterns after the
      fortification period. Homocysteine tended to decrease in supplement non-users and
      in subjects in the high alcohol, low fruit and vegetable dietary pattern (both P
      = 0.08). CONCLUSIONS: After fortification with folic acid, folate intake and
      plasma folate concentration increased significantly in all dietary patterns.
      There was a trend towards greatest homocysteine lowering in the high alcohol, low
      fruit and vegetable group.

PMID- 19105863
TI  - Prevalence and sociodemographic risk factors related to household food security
      in Aboriginal peoples in Canada.
AB  - OBJECTIVE: Canada's Aboriginal population is vulnerable to food insecurity and
      increasingly lives off-reserve. The Canadian Community Health Survey, Cycle 2.2
      Nutrition, was used to compare the prevalence and sociodemographic correlates of
      food insecurity between non-Aboriginal and off-reserve Aboriginal households.
      DESIGN: Food insecurity status was based on Health Canada's revised
      interpretation of responses to the US Household Food Security Survey Module.
      Logistic regression was used to assess if Aboriginal households were at higher
      risk for food insecurity than non-Aboriginal households, adjusting for household
      sociodemographic factors. SETTING: Canada. SUBJECTS: Households (n 35,107), 1528
      Aboriginal and 33 579 non-Aboriginal. RESULTS: Thirty-three per cent of
      Aboriginal households were food insecure as compared with 9 % of non-Aboriginal
      households (univariate OR 5.2, 95 % CI 4.2, 6.3). Whereas 14 % of Aboriginal
      households had severe food insecurity, 3 % of non-Aboriginal households did. The
      prevalence of sociodemographic risk factors for household food insecurity was
      higher for Aboriginal households. Aboriginal households were more likely to have
      three or more children (14 % v. 5 %), be lone-parent households (2 1 % v. 5 %),
      not have home ownership (52 % v. 31 %), have educational attainment of secondary
      school or less (43 % v. 26 %), have income from sources other than wages or
      salaries (38 % v. 29 %), and be in the lowest income adequacy category (33 % v.
      12 %). Adjusted for these sociodemographic factors, Aboriginal households
      retained a higher risk for food insecurity than non-Aboriginal households (OR
      2.6, 95 % CI 2.1, 3.2). CONCLUSIONS: Off-reserve Aboriginal households in Canada
      merit special attention for income security and poverty alleviation initiatives.

PMID- 19105864
TI  - Vitamin D status of Year 3 children and supplementation through schools with
      fortified milk.
AB  - OBJECTIVE: To evaluate levels of vitamin D3 and HDL-cholesterol (HDL-C), and the
      ratio of HDL-C to LDL-cholesterol (LDL-C), in schoolchildren receiving vitamin-D
      fortified, fat-depleted, high-Ca milk in schools. DESIGN: Cross-sectional study
      of previously randomised schools receiving supplemental milk, compared with a
      matched control group. SETTING: Low-decile Year 1-6 schools in the Waikato region
      of New Zealand. SUBJECTS: Year 3 children from either milk schools or control
      schools, consenting to blood sampling. RESULTS: For eighty-nine children
      receiving supplementary daily milk, vitamin D3 levels were significantly higher
      than in eighty-three control children matched for age, sex, body composition and
      ethnicity (mean (sd): 49.6 (15.8) v. 43.8 (14.7) nmol/l, P = 0.011), as were HDL
      C levels (mean (sd): 1.47 (0.35) v. 1.35 (0.29) mmol/l, P = 0.024) and HDL-C:LDL
      C (median: 0.79 v. 0.71, P = 0.026). LDL-C levels were similar in both groups
      (mean (sd): 2.07 (0.55) v. 2.16 (0.60) mmol/l, P = 0.31). Of control children,
      32/83 (20.2 %) of the milk group (Pearson's chi2 = 7.00, P = 0.008). Mean 25
      hydroxyvitamin D (vitamin D3) levels in the milk group were still below the lower
      end of the recommended normal range (60 nmol/l). CONCLUSIONS: Vitamin D3 levels
      are low in low-decile Year 3 children in midwinter. Levels are improved with
      vitamin-D-fortified milk but still below the recommended range. HDL-C and HDL
      C:LDL-C levels are improved in the milk-supplemented group. This supports the
      supply of vitamin-D-fortified, fat-reduced milk to schools.

PMID- 19105865
TI  - Determinants of ferritin and soluble transferrin receptors as iron status
      parameters in young adult women.
AB  - OBJECTIVE: To investigate associations between nutritional and non-nutritional
      variables and Fe status parameters, i.e. serum ferritin and soluble transferrin
      receptors (sTfR). DESIGN: Cross-sectional design. Fe status parameters were
      determined on a fasting venous blood sample. Nutritional variables were assessed
      using a 2 d food record and non-nutritional variables by a general questionnaire.
      A general linear model was used to investigate associations between the variables
      and Fe status parameters. SETTING: Region of Ghent, Dutch-speaking part of
      Belgium. SUBJECTS: Random sample of 788 women (aged 18-39 years). RESULTS: Median
      (interquartile range) ferritin and sTfR were 26.3 (15.9, 48.9) ng/ml and 1.11
      (0.95, 1.30) mg/l, respectively. BMI and alcohol intake were positively
      associated and tea intake was negatively associated with serum ferritin. Women
      who used a non-hormonal intra-uterine device, who gave blood within the past year
      or who had been pregnant within the past year had lower serum ferritin values
      than their counterparts. Significant determinants of sTfR were smoking habit and
      pregnancy, with higher values for non-smokers and women who had been pregnant
      within the past year. CONCLUSIONS: The present study indicates that contraceptive
      use, time since last blood donation, time since last pregnancy, BMI, alcohol and
      tea intake are determinants of Fe stores, whereas smoking habit and time since
      last pregnancy are determinants of tissue Fe needs. When developing strategies to
      improve Fe status, special attention should be given to women who use a non
      hormonal intra-uterine device, gave blood within the past year and had been
      pregnant within the past year.

PMID- 19105866
TI  - Socio-environmental, personal and behavioural predictors of fast-food intake
      among adolescents.
AB  - OBJECTIVE: To identify the socio-environmental, personal and behavioural factors
      that are longitudinally predictive of changes in adolescents' fast-food intake.
      DESIGN: Population-based longitudinal cohort study. SETTING: Participants from
      Minnesota schools completed in-class assessments in 1999 (Time 1) while in middle
      school and mailed surveys in 2004 (Time 2) while in high school. SUBJECTS: A
      racially, ethnically and socio-economically diverse sample of adolescents (n
      806). RESULTS: Availability of unhealthy food at home, being born in the USA and
      preferring the taste of unhealthy foods were predictive of higher fast-food
      intake after 5 years among both males and females. Among females, personal and
      behavioural factors, including concern about weight and use of healthy weight
      control techniques, were protective against increased fast-food intake. Among
      males, socio-environmental factors, including maternal and friends' concern for
      eating healthy food and maternal encouragement to eat healthy food, were
      predictive of lower fast-food intake. Sports team participation was a strong risk
      factor for increased fast-food intake among males. CONCLUSIONS: Our findings
      suggest that addressing socio-environmental factors such as acculturation and
      home food availability may help reduce fast-food intake among adolescents.
      Additionally, gender-specific intervention strategies, including working with
      boys' sports teams, family members and the peer group, and for girls, emphasizing
      the importance of healthy weight-maintenance strategies and the addition of
      flavourful and healthy food options to their diet, may help reduce fast-food
      intake.

PMID- 19105867
TI  - Multilevel modelling of sociodemographic predictors of various levels of anaemia
      among women in Mali.
AB  - OBJECTIVE: Anaemia currently affects 40-80% of women in Africa. While risk
      factors for anaemia have been intensively studied, research has rarely compared
      risk factors between mild anaemia and moderate/severe anaemia. Also, the
      contribution of neighbourhood to the prevalence of anaemia has been rarely
      studied. The aim of the present study was to identify and compare individual and
      contextual factors associated with various levels of anaemia among women. DESIGN:
      A multilevel analysis of data from the 2001 Mali Demographic and Health Survey (n
      3763) was carried out. Outcomes variables were mild anaemia, moderate-to-severe
      anaemia and any anaemia. Multilevel regression analyses were performed for each
      outcome. SETTING: Mali, West Africa. SUBJECTS: Women (n 3763) aged 15 to 49
      years, including 512 pregnant women. RESULTS: Among the eleven potential risk
      factors included in the models, two factors were associated with mild anaemia
      (BMI and education), three with any anaemia (pregnancy, BMI and education) and
      six with moderate-to-severe anaemia (pregnancy, BMI, education, wealth, childhood
      residency and region of residence). Clustering of anaemia within communities was
      20% for moderate-to-severe anaemia and 13% for mild anaemia. Despite significant
      differences in the prevalence of anaemia across regions in Mali, no difference
      between regions in the risk of mild anaemia was found and only the region of Gao
      showed a significantly higher risk of moderate-to-severe anaemia. CONCLUSIONS:
      The findings indicate that sociodemographic risk factors as well as clustering of
      anaemia varies with the severity of anaemia. Specific studies are needed to
      identify risk factors of mild anaemia as well as its consequences, as mild
      anaemia accounts for 20-40% of total prevalence of anaemia in Africa.

PMID- 19105868
TI  - Maternal perceptions of their child's weight status: the GENESIS study.
AB  - OBJECTIVE: The objective of the present work was to quantify mothers'
      misclassification of pre-school children's weight status and to determine factors
      associated with the maternal misperception. DESIGN: A representative sample of
      2287 children aged 2-5 years was examined (GENESIS study). Mothers' perceptions
      of their child's weight status and the children's and mothers' anthropometric and
      other characteristics (sociodemographic and lifestyle) were recorded. RESULTS:
      Almost 38 % of mothers underestimated their child's weight status. The frequency
      of underestimation was much higher among 'at risk of being overweight' and
      'overweight' children (88.3 % and 54.5 %, respectively) compared with
      'underweight/normal-weight' children (18.0 %, P < 0.001). Multiple logistic
      regression modelling revealed that the likelihood of mothers' underestimation of
      their child's weight status was significantly higher in boys, in children
      engaging in physical activity for less than 3 h/week and in children whose
      mothers had low education status, compared with their counterparts. Moreover, the
      higher the BMI-for-age Z-score, the greater the odds that the mother would
      underestimate her child's weight status. CONCLUSIONS: The current study
      demonstrated that more than one-third of mothers misclassify their children's
      weight status as being lower than the actual. Given that mother's weight
      perception might be an important determinant of child's body weight development,
      clinicians and health professionals should help mothers correctly classify their
      children's weight status, which could potentially help in the early prevention of
      overweight and obesity.

PMID- 19105869
TI  - Community-specific modifications are essential for objective assessment of
      maternal dietary intake--Pune Maternal Nutrition Study.
AB  - OBJECTIVE: To introduce community-specific modifications in the conventional 24 h
      recall method for objectively estimating maternal dietary intake and validate it
      with a reference method. DESIGN: A modified 24 h recall method was developed with
      the visit of trained local girls at the subject's home to weigh portion sizes at
      each mealtime over the 24 h recall period. This was validated with the reference
      method in which weighed records of the foods consumed were obtained and their
      laboratory analysis was done to obtain nutrient intakes. SETTING: Rural areas
      located 40-50 km from Pune City, India. SUBJECTS: Forty-one pregnant women
      participated willingly. RESULTS: The estimates of intake obtained from the
      reference method were comparable to those obtained from the modified 24 h recall
      method for energy (7795 (sd 1841) kJ (1863 (sd 440) kcal) v. 7615 (sd 1824) kJ
      (1820 (sd 436) kcal), respectively), protein (48.6 (sd 12.9) g v. 45.3 (sd 12.6)
      g, respectively) and fat (35.3 (sd 16.6) g v. 36.0 (sd 14.2) g, respectively).
      Significant correlation was observed between the estimates obtained by the two
      methods for energy (0.75, P < 0.001), protein (0.71, P < 0.001) and fat (0.56, P
      < 0.001) and differences in nutrient intake did not reveal any systematic bias.
      When compared with the reference method, the modified method showed >80%
      sensitivity and specificity for identifying inadequate maternal energy intakes.
      CONCLUSIONS: Simple modifications to conventional methods backed by understanding
      of community specifics and nutritional peculiarities are of immense importance in
      obtaining objective estimates of daily nutritional intakes of individuals in free
      living populations. The approach would be adaptable in similar settings in other
      developing countries.

PMID- 19105870
TI  - The Cambridge Declaration: towards clinical trials for drug-resistant
      tuberculosis.

PMID- 19105871
TI  - A bigger and better International Journal of Tuberculosis and Lung Disease.

PMID- 19105872
TI  - The infectiousness of laryngeal tuberculosis: appropriate public health action
      based on false premises.

PMID- 19105873
TI  - Providing HIV care for co-infected tuberculosis patients: a perspective from sub
      Saharan Africa.
AB  - Human immunodeficiency virus/acquired immune-deficiency syndrome (HIV/AIDS) and
      tuberculosis (TB) are overlapping epidemics that cause an immense burden of
      disease in sub-Saharan Africa. This region is home to the majority of the world's
      co-infected patents, who have higher TB case fatality and recurrence rates than
      patients with TB alone. A World Health Organization interim policy has been
      developed to reduce the joint burden of TB-HIV disease, an important component of
      which is provision of HIV care to co-infected patients. This review focuses on
      HIV testing of TB patients and, for those who are HIV-positive, the
      administration of adjunctive cotrimoxazole preventive treatment (CPT) and
      antiretroviral treatment (ART). HIV testing has moved from a voluntary, client
      initiated intervention to one that is provider-initiated and a routine part of
      the diagnostic work-up. The efficacy and safety of CPT in HIV-infected patients
      is now well established, and this is an essential part of the package of HIV
      care. ART scale-up in Africa can substantially improve outcomes in co-infected
      patients. However, the clinical and programmatic challenges of combining ART with
      anti-tuberculosis treatment need to be resolved to realise the full potential of
      this benefit. These include the optimal time to start ART, how best to combine
      rifampicin-containing regimens with first-line and second-line ART regimens,
      management of immune reconstitution disease, the role of isoniazid preventive
      treatment with ART after TB treatment completion, and where and how to provide
      combined treatment to best suit the patient. Clinical and operational studies in
      the next few years should help to resolve some of these issues.

PMID- 19105874
TI  - Risk factors associated with recent transmission of tuberculosis: systematic
      review and meta-analysis.
AB  - A systematic review of published articles was performed to identify risk factors
      associated with recent transmission of tuberculosis (TB). The computerized search
      identified studies in PubMed, Ovid, CDSR, CINAHL and EMBASE published between
      1994 and 2005. Of 137 articles, 30 satisfied all the inclusion criteria for meta
      analysis. A random effects model estimated the odds ratio (OR), confidence
      interval (CI), and heterogeneity between studies. Recent transmission of TB was
      associated with: ethnic minority (OR 3.03, 95%CI 2.21- 4.16), being a native of
      the country (OR 2.33, 95%CI 1.76-3.08), residing in an urban area (OR 1.52, 95%CI
      1.35-1.72), drug use (OR 3.01, 95%CI 2.14-4.22), excessive alcohol consumption
      (OR 2.27, 95%CI 1.69-3.06), homelessness (OR 2.87, 95%CI 2.04-4.02), previous
      incarceration (OR 2.21, 95%CI 1.71-2.86), human immunodeficiency virus
      infection/acquired immune-deficiency syndrome (OR 1.66, 95%CI 1.36-2.05), young
      age (OR 2.09, 95%CI 1.69-2.59), sputum smear positivity (OR 1.39, 95%CI 1.20
      1.60) and male sex (OR 1.37, 95%CI 1.19-1.58). The results should be useful for
      improving prevention and control strategies, thus contributing to a reduction in
      Mycobacterium tuberculosis transmission.

PMID- 19105875
TI  - Protecting patients' rights, ensuring safety and quality assurance in
      tuberculosis prevalence surveys.
AB  - The conduct of biomedical studies is guided by statements of internationally
      recognised principles of human rights. The first principle of the Nuremberg Code
      was the centrality of voluntary participation of subjects with informed consent.
      All prevalence surveys should be reviewed by the appropriate ethics review
      committees. Each potential survey participant should be adequately informed of
      the aims, methods and sources of funding of the survey, any possible conflicts of
      interest, the institutional affiliations of the researchers, the anticipated
      benefits and potential risks of the study, and any discomfort it may entail.
      Attention should be paid to safety in each component of the survey. Test
      procedures that require particular attention are chest radiography (CXR) and
      bacteriological examination. Quality assurance should be applied to all aspects
      of research and, in particular, to any measurements undertaken, including CXR
      assessments, laboratory examinations and questionnaire and data management.
      Furthermore, to ensure comparability of data from different surveys, it is
      important to apply the same survey design and methodology and to use the same
      reporting format.

PMID- 19105876
TI  - Annual risks of tuberculous infection in East Nusa Tenggara and Central Java
      Provinces, Indonesia.
AB  - SETTING: East Nusa Tenggara (NTT) and Central Java Provinces, Indonesia.
      OBJECTIVE: To estimate the average annual risk of tuberculous infection (ARTI)
      among school children aged 6-9 years in each province. METHODS: Children
      attending Classes 1-4 in 65 schools in NTT and 79 in Central Java, selected by
      two-stage sampling, were intradermally administered 2 tuberculin units of
      purified protein derivative RT23 with Tween 80 on the mid-volar aspect of the
      left forearm. The maximum transverse diameter of induration was measured 72 h
      later. The analysis was carried out among 5479 satisfactorily test-read children
      in NTT and 6943 in Central Java. One hundred and fifty-five new sputum smear
      positive pulmonary tuberculosis (PTB) cases (78 in NTT and 77 in Central Java)
      were also tuberculin tested. Based on the frequency distribution of reaction
      sizes among the children and PTB cases, the prevalence of infection was estimated
      by the mirror-image method using the modes of tuberculous reactions at 15 and 17
      mm. RESULTS: Using the 15 mm mode, ARTI was estimated at 1% in NTT and 0.9% in
      Central Java. Using the 17 mm mode, ARTI was estimated at 0.5% in NTT and 0.4% in
      Central Java. CONCLUSION: Transmission of tuberculous infection may be further
      reduced by intensification of tuberculosis control efforts.

PMID- 19105877
TI  - Prevalence of latent tuberculosis infection among gold miners in South Africa.
AB  - SETTING: South African gold mines. OBJECTIVE: To determine the prevalence of
      latent tuberculosis infection (LTBI) and risk factors for a positive tuberculin
      skin test (TST) among gold miners. DESIGN: Cross-sectional survey. Human
      immunodeficiency virus (HIV) status was determined by self-report and medical
      records. TST positivity was defined by the mirror method to estimate the
      prevalence of LTBI, and by the US Centers for Disease Control and Prevention
      definitions to explore risk factors at the individual level. RESULTS: Among 429
      participants (105/130 subjects aged <30 years, 324/390 > or = 30 years), the
      estimated prevalence of LTBI was 89%; 45.5% of HIV-positive participants had a
      zero TST response compared to respectively 13% and 13.5% in the HIV-negative and
      status unknown participants. In participants with TST > 0, there was no
      significant difference between size of response by HIV status: the mean (standard
      deviation) widths for HIV-positive, HIV-negative and HIV status unknown were
      respectively 11.84 (2.75), 12.03 (2.75) and 12.52 mm (3.04) (analysis of variance
      P = 0.28). Factors independently associated with a TST < 10 mm were positive HIV
      status (aOR 0.41, 95%CI 0.17-0.96) and not working underground (aOR 0.25, 95%CI
      0.09-0.71). CONCLUSIONS: The prevalence of LTBI is very high in gold miners in
      South Africa. HIV-infected individuals are more likely to have a negative TST,
      but HIV infection does not affect the size of TST response.

PMID- 19105878
TI  - A simple screening tool for active tuberculosis in HIV-infected adults receiving
      antiretroviral treatment in Uganda.
AB  - SETTING: Reliable clinical algorithms that screen for active tuberculosis (TB) in
      human immunodeficiency virus (HIV) infected people initiating or receiving
      antiretroviral treatment (ART) in sub-Saharan Africa could reduce the need for
      diagnostic procedures. METHODS: We estimated the utility of six TB-related signs
      and symptoms, alone or in combination, compared with the Uganda Ministry of
      Health diagnostic guidelines for participants with prevalent (baseline), early
      ART (< or = 3 months on ART) and incident TB (>3 months on ART). RESULTS: Of 1995
      participants screened for ART eligibility, 71 (3.6%) had prevalent TB. The
      presence of any one of the following: cough > or = 3 weeks, fever > or = 4 weeks,
      lymphadenopathy or baseline body mass index < or = 18 kg/m(2) had a sensitivity
      of 99% (95%CI 96-100), a specificity of 66% (95%CI 64-68) and a negative
      predictive value (NPV) of 100% (95%CI 99-100) for predicting active TB. During
      ART follow-up, TB incidence was 2.4 (95%CI 1.6-3.4)/100 person-years. The
      presence of cough > or = 3 weeks or general weakness was 100% sensitive (95%CI 99
      100), 66% specific (95%CI 59-74) and had an NPV of 100% (95%CI 99-100).
      CONCLUSION: Use of a simple TB screening algorithm can accurately identify, in a
      resource-poor African setting, HIV-infected individuals who require further
      procedures to diagnose active TB.

PMID- 19105879
TI  - Prevalence of anti-tuberculosis drug resistance in an HIV/AIDS reference hospital
      in Rio de Janeiro, Brazil.
AB  - SETTING: A reference hospital for tuberculosis (TB) and human immunodeficiency
      virus/acquired immune-deficiency syndrome (HIV/AIDS) with a TB control programme
      in Rio de Janeiro, Brazil. OBJECTIVE: To estimate the prevalence of resistance to
      anti-tuberculosis drugs and to identify associated factors. DESIGN: In a cross
      sectional study, clinical and laboratory data were collected retrospectively from
      2001 to 2005. Patients with isolation of Mycobacterium tuberculosis and available
      drug susceptibility tests were considered eligible. Data on demographic
      characteristics, risk factors for resistance, HIV serology and past TB history
      were collected and analysed by chi(2) Mann-Whitney test and Poisson regression.
      RESULTS: We analysed 350 treatments, of which 62 were for patients with previous
      TB. HIV status was positive in 31.2% of cases. Resistance was found in 15.7% and
      multidrug resistance (MDR) in 4.3% of cases. Previous treatment (P < 0.001) and
      relapse within 2 years were associated with resistance (P < 0.03). Pulmonary
      cavities were associated with MDR (P < 0.001). Homelessness was associated with
      any resistance in newly diagnosed patients (P < 0.01). Working in a hospital was
      not associated with resistance. CONCLUSION: Suspicion of drug-resistant disease
      is necessary in patients with a history of previous TB in hospitals in Rio de
      Janeiro. The implementation of an effective hospital TB control programme can
      prevent transmission even in high TB prevalence settings.

PMID- 19105880
TI  - Evolution in the resistance of Mycobacterium tuberculosis to anti-tuberculosis
      drugs in Nicaragua.
AB  - SETTING: Nicaragua, a country where the DOTS strategy has been successfully
      implemented since 1984. OBJECTIVE: To estimate the prevalence and trends of
      Mycobacterium tuberculosis resistance to first-line anti-tuberculosis drugs.
      DESIGN: A prospective national survey carried out in 2004 according to the
      standardised model developed by the World Health Organisation and the
      International Union Against Tuberculosis and Lung Disease. RESULTS: A total of
      423 M. tuberculosis strains were studied. Among the 320 strains evaluated for
      initial resistance, 13.1% displayed resistance to any drug, lower than the 1998
      figure of 15.6%. Overall initial resistance to isoniazid (INH), rifampicin (RMP)
      and multidrug resistance (MDR) was respectively 6.6%, 0.9% and 0.6%. Initial
      resistance was higher in older age groups. Overall acquired resistance was 35.9%
      (n = 103); resistance to INH was 29.3% and to RMP 8.9%, while MDR was 7.9%. The
      acquired MDR rate was clearly higher in Category I failures (44.4%) than in
      relapses (3.8%) and retrieved defaulters (2.7%). All resistance rates found in
      this study were lower than those detected in 1998. CONCLUSION: This study shows
      low rates of resistance and MDR and a downward trend in all rates, undoubtedly
      related to the proper implementation of the National Tuberculosis Programme.

PMID- 19105881
TI  - Prevalence and risk factors for multidrug-resistant tuberculosis in the Republic
      of Georgia: a population-based study.
AB  - SETTING: Multidrug-resistant tuberculosis (MDR-TB, defined as resistance to at
      least isoniazid and rifampicin) has emerged as a serious global public health
      problem, especially in the former Soviet republics. The extent of the problem in
      Georgia has been incompletely defined. OBJECTIVE: To determine the prevalence and
      risk factors for MDR-TB in Georgia. DESIGN: A population-based study was carried
      out between July 2005 and May 2006. RESULTS: Of 1314 patients with acid-fast
      bacilli smear- and culture-positive pulmonary tuberculosis (TB), 799 (60.8%) were
      newly diagnosed patients and 515 (39.2%) had been treated previously. Overall,
      733 (56%) patients had resistance to at least one anti-tuberculosis drug and 195
      (15%) had MDR-TB. Patients who had been treated previously for TB were
      significantly more likely to have MDR-TB than newly diagnosed patients (141/515
      [27.4%] vs. 54/794 [6.8%], OR 5.27, 95%CI 3.75-7.41). In multivariate analysis,
      previous TB treatment (aOR 5.47, 95%CI 3.87-7.74) and female sex (aOR1.58, 95%CI
      1.02-2.32) were independent risk factors for the presence of MDR-TB. CONCLUSIONS:
      Drug-resistant TB, including MDR-TB, has emerged as a major public health problem
      in Georgia. Further TB control efforts need to be implemented to prevent the
      development of new cases of MDR-TB and to treat existing patients with MDR-TB.

PMID- 19105882
TI  - Acquired drug resistance pattern in tuberculosis cases at the State Tuberculosis
      Centre, Delhi, India.
AB  - SETTING: State TB Demonstration Centre, Delhi, India. OBJECTIVE: To obtain a
      baseline estimate of the prevalence of multidrug-resistant tuberculosis (MDR-TB)
      among previously treated tuberculosis (TB) cases at the State Tuberculosis Centre
      in 2006. DESIGN: A retrospective study. Drug susceptibility data of 5252
      previously treated patients tested at this centre were analysed. RESULTS: Of 2880
      Mycobacterium tuberculosis isolates from previously treated cases, 1498 (52%)
      were resistant to one or more anti-tuberculosis drugs, of which 47.1% were MDR.
      Resistance to isoniazid was observed in all resistant isolates, followed by
      resistance to rifampicin in 1357 (47.1%), streptomycin in 403 (14.2%) and
      ethambutol in 107 (3.72%). A significantly higher rate of resistance, including
      MDR, was observed among treatment failures compared to relapses and defaulters.
      CONCLUSION: A very high proportion of drug-resistant cases had MDR besides
      resistance to two or more drugs. This proportion was significantly higher among
      treatment failures compared to relapses and treatment after default cases,
      underlining the need for early identification of treatment failure by early
      referral for culture and drug susceptibility testing, and initiation of
      appropriate treatment.

PMID- 19105883
TI  - Increasing incidence of fluoroquinolone-resistant Mycobacterium tuberculosis in
      Mumbai, India.
AB  - SETTING: Tertiary referral centre, private hospital, Mumbai, India. OBJECTIVE: To
      analyse the incidence of fluoroquinolone (FQ) resistant Mycobacterium
      tuberculosis (TB) in our laboratory from 1995 to 2004. DESIGN: Retrospective
      review and analysis of the drug susceptibility test records of all M.
      tuberculosis culture-positive samples from our Microbiology Department from 1995
      to 2004. RESULTS: FQ resistance has increased exponentially in our laboratory,
      from 3% in 1996 to 35% in 2004. The incidence of multidrug-resistant tuberculosis
      has also increased during the same period, from 33% in 1995 to 56% in 2004.
      CONCLUSION: The incidence of FQ-resistant M. tuberculosis is gradually increasing
      to alarming levels. This may be due to widespread use of this vital group of
      drugs in the treatment of community-acquired infections. We urge that these broad
      spectrum antibiotics be used judiciously, and ideally be reserved for treatment
      of resistant TB in TB-endemic areas.

PMID- 19105885
TI  - Risk of active tuberculosis in adult household contacts of smear-positive
      pulmonary tuberculosis cases.
AB  - SETTING: Seven public tuberculosis (TB) dispensaries in Istanbul, Turkey.
      OBJECTIVE: To investigate the risk of active TB among adult household contacts
      (age > or = 15 years) of newly diagnosed sputum smear-positive pulmonary TB (PTB)
      cases in Istanbul. DESIGN: A retrospective analysis of adult household contacts
      of 1570 pulmonary TB cases registered at seven TB dispensaries in Istanbul
      between 1997 and 2000. RESULTS: A total of 6188 household contacts (mean
      contact/index case: 3.9) were included in the study, of whom 4114 (67%) were aged
      > or = 15 years (mean contact/index case: 2.6); 3310 (80.5%) of these
      participated in a contact investigation. The mean duration of follow-up was 2.2
      years (range 1-4 years); 222 active TB cases (rate 5.4%, 95%CI 5.2-5.6) were
      detected, 171 within the first year. The incidence of active TB was 2491/100 000
      (3555/100 000 in the 15-34 year age group and 1195/100 000 in the > or = 35 year
      age group, P < 0.0001). Rates of active TB were highest in the 15-24 year (8.5%)
      and 25-34 year (6.5%) age groups. CONCLUSION: The incidence of active TB among
      adult household contacts of sputum smear-positive PTB cases was high. This high
      incidence justifies the prescription of chemopropylaxis not only for children but
      also for all contacts, especially those aged between 15 and 34 years.

PMID- 19105884
TI  - T-cell assay conversions and reversions among household contacts of tuberculosis
      patients in rural India.
AB  - BACKGROUND: Interferon-gamma assays (IGRAs) are alternatives to the tuberculin
      skin test (TST), but IGRA conversions and reversions are not well understood. In
      a pilot study, we determined conversions and reversions using QuantiFERON-TB Gold
      In-Tube((R)) (QFT) among household contacts of TB cases, and evaluated the effect
      of using various definitions and criteria for conversions. DESIGN: In a cohort of
      250 contacts in India, 46% were TST-positive at baseline and 54% were QFT
      positive. We re-tested this cohort after 12 months. Conversion rates were
      estimated using several definitions. RESULTS: Of the 250 contacts, 205 (82%)
      underwent repeat testing. Among 85 contacts with baseline TST-negative/QFT
      negative results, TST conversion rates ranged between 7.5% and 13.8%, and QFT
      conversion rates ranged between 11.8% and 21.2%, depending on the definitions
      used. Among 109 contacts who were QFT-positive at baseline, seven (6.4%) had QFT
      reversions. QFT reversions were most likely when the baseline TST was negative
      and QFT results were just above the diagnostic cut-off. CONCLUSIONS: QFT
      conversions and reversions occurred among contacts of TB cases. Conversion rates
      seemed to vary, depending on the test and definitions used for conversions. These
      findings need to be verified in larger studies in various settings.

PMID- 19105886
TI  - Simple measures are as effective as invasive techniques in the diagnosis of
      pulmonary tuberculosis in Malawi.
AB  - SETTING: Detection of smear-positive pulmonary tuberculosis (PTB) cases is vital
      for tuberculosis (TB) control. Methods to augment sputum collection are
      available, but their additional benefit is uncertain in resource-limited
      settings. OBJECTIVE: To compare the diagnostic yields using five methods to
      obtain sputum from adults diagnosed with smear-negative PTB in Malawi. DESIGN:
      Self-expectorated sputum was collected under supervision for microscopy and
      mycobacterial culture in the study laboratory. Confirmed smear-negative patients
      provided physiotherapy-assisted sputum and induced sputum, followed the next
      morning by gastric washing and bronchoalveolar lavage (BAL) samples. RESULTS: A
      total of 150 patients diagnosed with smear-negative PTB by the hospital service
      were screened; 39 (26%) were smear-positive from supervised self-expectorated
      sputum examined in the study laboratory. The remaining 111 confirmed smear
      negative patients were enrolled in the study; 89% were human immunodeficiency
      virus positive. Seven additional smear-positive cases were diagnosed using the
      augmented sputum collection techniques. No differences were observed in the
      numbers of cases detected using the different methods. Of the 46 smear-positive
      cases, 44 (95.6%) could be detected from self-expectorated and physiotherapy
      assisted samples. CONCLUSIONS: For countries such as Malawi, the best use of
      limited resources to detect smear-positive PTB cases would be to improve the
      quality of self-expectorated sputum collection and microscopy. The additional
      diagnostic yield using BAL after induced sputum is limited.

PMID- 19105887
TI  - Tuberculosis outcomes in Taipei: factors associated with treatment interruption
      for 2 months and death.
AB  - SETTING: All individuals reported as being treated for pulmonary tuberculosis
      (PTB) among citizens of Taipei City, Taiwan, in 2003. OBJECTIVES: To investigate
      risk factors associated with treatment interruption for at least 2 consecutive
      months and death. DESIGN: The outcome of PTB cases was determined by consulting
      medical charts. RESULTS: Of 1127 PTB patients registered, 824 (73.1%) were
      successfully treated, 189 (16.8%) died, 65 (5.8%) interrupted treatment, 17
      (1.5%) were still on treatment 15 months after commencing treatment and 32 (2.8%)
      failed. The only significant factor associated with treatment interruption was
      visits to other health facilities after commencing tuberculosis (TB) treatment.
      TB patients had a standardised mortality ratio of 8.7 (95%CI 7.5-10.0). Factors
      significantly associated with death were age (adjusted hazard ratio [adjHR] 1.06.
      95%CI 1.05-1.08), sputum culture not performed/unknown (adjHR 2.07, 95%CI 1.47
      2.92), and comorbidity with respiratory disease (adjHR 1.68, 95%CI 1.24-2.27),
      infectious disease (adjHR 2.80, 95%CI 2.07-3.78), renal disease (adjHR 2.58,
      95%CI 1.82-3.66) or cancer (adjHR 3.31, 95%CI 2.35-4.65), compared with other
      patients. CONCLUSION: Visits to other health facilities were associated with
      interruption of treatment for at least 2 months. A high proportion of deaths was
      due to old age and comorbidity.

PMID- 19105888
TI  - Impact of advocacy on the tuberculosis management practices of private
      practitioners in Chennai City, India.
AB  - BACKGROUND: Innovative schemes to ensure the participation of private
      practitioners (PPs) in the Revised National Tuberculosis Control Programme
      (RNTCP) are necessary to identify and treat all patients with tuberculosis (TB).
      We developed a novel public-private mix (PPM) model to encourage PPs to practise
      DOTS and participate in the RNTCP while retaining their patients. METHODS: The
      Resource Group for Education and Advocacy for Community Health (REACH) developed
      and implemented the programme in partnership with the Chennai local health
      authority and the Tuberculosis Research Centre, Chennai, India. PPs were
      sensitised to the RNTCP and DOTS through a one-to-one approach or group meetings,
      and were assisted in referring patients. Surveys were carried out at baseline and
      at the completion of the study to assess changes in attitudes and practices.
      RESULTS: Six hundred PPs underwent sensitisation about the RNTCP, after which the
      proportion of PPs adopting DOTS increased significantly (P < 0.001), and the
      majority (72.8%) used sputum testing for diagnosing TB. The proportion of PPs who
      used X-ray alone for diagnosis declined to 16.0% from a baseline of 45.4%.
      CONCLUSIONS: This PPM model, which emphasises sustained advocacy for DOTS and
      allows PPs to retain private patients, looks promising and needs to be tested at
      other sites.

PMID- 19105889
TI  - Influence of a single oral dose of vitamin D(2) on serum 25-hydroxyvitamin D
      concentrations in tuberculosis patients.
AB  - SETTING: Newham Chest Clinic, London, UK. OBJECTIVE: To determine the safety and
      efficacy of the administration of bolus-dose vitamin D(2) in elevating serum 25
      hydroxyvitamin D (25[OH]D) concentrations in tuberculosis (TB) patients. DESIGN:
      A multi-ethnic cohort of TB patients was randomised to receive a single oral dose
      of 2.5 mg vitamin D(2) (n = 11) or placebo (n = 14). Serum 25(OH)D and corrected
      calcium concentrations were determined at baseline and 1 week and 8 weeks post
      dose, and compared to those of a multi-ethnic cohort of 56 healthy adults
      receiving an identical dose of vitamin D(2). RESULTS: Hypovitaminosis D (serum
      25[OH]D < 75 nmol/l) was present in all patients at baseline. A single oral dose
      of 2.5 mg vitamin D2 corrected hypovitaminosis D in all patients in the
      intervention arm of the study at 1 week post-dose, and induced a 109.5 nmol/l
      mean increase in their serum 25(OH)D concentration. Hypovitaminosis D recurred in
      10/11 patients at 8 weeks post-dose. No patient receiving vitamin D(2)
      experienced hypercalcaemia. Patients receiving 2.5 mg vitamin D(2) experienced a
      greater mean increase in serum 25(OH)D at 1 week post-dose than healthy adults
      receiving 2.5 mg vitamin D(2). CONCLUSION: A single oral dose of 2.5 mg vitamin
      D(2) corrects hypovitaminosis D at 1 week but not at 8 weeks post-dose in TB
      patients.

PMID- 19105890
TI  - Variations in quality of carbol fuchsin stains collected from routine
      tuberculosis laboratories.
AB  - SETTING: In-use carbol fuchsin stains were collected from 10 different routine
      acid-fast bacilli smear microscopy laboratories. OBJECTIVE: To examine the
      variations in the composition of carbol fuchsin stains. METHOD: Carbol fuchsin
      concentrations were first determined spectrophotometrically by measuring
      absorbance at 547 nm. High-performance liquid chromatography (HPLC) separated and
      quantified the four basic fuchsin homologues: para-rosaniline, rosaniline,
      magenta II and new fuchsin, and identity was confirmed by mass spectrometry (MS).
      RESULTS: Absorbance measurement showed that three of 10 (30%) samples contained
      insufficient carbol fuchsin (<70%). Wide variations in relative proportions of
      fuchsin homologues were found. CONCLUSION: The relative abundance of rosaniline +
      new fuchsin was quite stable among the different laboratories. Spectrophotometry
      and HPLC/MS are necessary and sensitive tools for monitoring fuchsin quality.

PMID- 19105891
TI  - Evaluating the performance of basic fuchsin for the Ziehl-Neelsen stain.
AB  - SETTING: An investigation of commercially available basic fuchsin (BF) dye
      powders used for the detection of acid-fast bacilli (AFB). OBJECTIVE: To
      determine whether single, or multiple, assays may predict the performance of BF
      in the Ziehl-Neelsen (ZN) method. DESIGN: The composition and staining properties
      of six BF dye samples were assessed using continuous recording spectrophotometry,
      reverse phase thin-layer chromatography (RPTLC) and a standardised ZN biological
      staining test. RESULTS: Variable proportions of BF homologues could be
      demonstrated in the samples, but neither spectroscopy nor RPTLC was fully
      predictive of their staining quality. ZN staining of standard smears was needed
      to identify five powders that yielded satisfactory results and one powder with
      unsatisfactory performance. Increasing the BF concentration did not always result
      in improved staining. CONCLUSIONS: Simple analytical methods, such as
      spectrophotometry and RPTLC, should be complemented by biological staining of
      control smears to assess the quality of BF dye powders. This allows tuberculosis
      control programmes to avoid procurement of BF dyes that would fail to detect AFB
      even when strictly adhering to current international guidelines for ZN staining.

PMID- 19105892
TI  - Validation of bleach-treated smears for the diagnosis of pulmonary tuberculosis.
AB  - SETTING: Health centres in Awassa, southern Ethiopia. DESIGN: Consecutive
      patients visiting health centre laboratories for the evaluation of suspected
      pulmonary tuberculosis (TB) between June and September 2006 were investigated. On
      the-spot, morning and second on-the-spot sputum samples were pooled for each
      patient. Direct smears were stained with hot Ziehl-Neelsen (ZN) technique and
      aliquots cultured for mycobacteria on Lowenstein-Jensen media. The remaining
      sputum was treated with household bleach, aliquoted and processed with short-term
      digestion, centrifugation and sedimentation techniques, and stained with ZN.
      RESULTS: Acid-fast bacilli were detected in respectively 126 (25%), 141 (28%),
      169 (34%) and 198 (40%) of the 497 pooled sputum samples processed by the direct,
      short-term, sedimentation and centrifugation techniques (P < 0.001). The
      sensitivity of the direct, short-term, sedimentation and centrifugation
      techniques was respectively 51.1%, 53.2%, 57.6% and 63.6%. The difference between
      the direct smear and centrifugation (P < 0.001) or sedimentation (P < 0.005)
      methods was significant. The specificity of the direct, short-term digestion,
      sedimentation and centrifugation techniques was respectively 97%, 93%, 86.5% and
      80.8%. CONCLUSIONS: Bleach treatment of sputum and centrifugation significantly
      improves the sensitivity of smear microscopy for the diagnosis of TB in a health
      centre in a high TB burden area. It is more sensitive, but possibly less
      specific, than other bleach methods.

PMID- 19105893
TI  - Reduction in asthma morbidity following a community-based asthma self-management
      programme in Tonga.
AB  - BACKGROUND: The Tonga Asthma Self-management Project assessed whether the
      introduction of an asthma self-management plan would reduce asthma morbidity.
      METHODS: The project involved a 'before and after' trial, with each participant
      serving as his/her own control. Asthma patients used the self-management plan to
      manage their asthma medication or obtain medical help based on their peak
      expiratory flow (PEF) rate and/or asthma symptoms. RESULTS: The 110 participants
      initially had relatively high asthma morbidity: 68% had had an emergency medical
      visit for asthma in the previous 12 months. Ninety-two (84%) completed the 12
      month programme. Emergency doctor visits fell from 66% in the previous 12 months
      to 18% (P < 0.001) in the following 12 months. Other measures also improved,
      including hospital admissions (from 19% to 3%, P = 0.001), having 14 days or more
      'out of action' (from 29% to 4%, P < 0.001), waking > or = 2 nights a week (from
      40% to 13%, P < 0.001), severe asthma attacks (from 54% to 18%, P < 0.001) and
      mean PEF rates (from 341 l/min to 417 l/min, a 22% increase, P < 0.001).
      CONCLUSIONS: The potential benefits of asthma self-management plans and community
      based asthma education are supported by the findings of the Tonga study. Their
      implementation is essential in the resource-scarce Pacific health setting.

PMID- 19105894
TI  - Normal chest radiographs in sputum culture-positive pulmonary tuberculosis.

PMID- 19105895
TI  - Induced sputum for diagnosis of cryptococcal pneumonia in Botswana.

PMID- 19105896
TI  - Who determines the 'standard of care' in research in resource poor countries?

PMID- 19105898
TI  - Anti-fungal efficacy of polybutylcyanoacrylate nanoparticles of allicin and
      comparison with pure allicin.
AB  - Although garlic has been used in Chinese traditional medicine for its medical
      properties for thousands of years, investigations into its mode of action are
      relatively recent. The purpose of this study was to evaluate the in vitro anti
      fungal efficacy of the active principle of garlic, pure allicin and
      polybutylcyanoacrylate (PBCA) nanoparticles (NPs) loaded with allicin. Pure
      allicin was prepared by reacting synthetic alliin with a stabilized process of
      the garlic enzyme alliinase. PBCA NPs were prepared by emulsion polymerization
      method and pure allicin was wrapped into it. The in vitro efficacy of pure
      allicin and PBCA-allicin NPs to Candida albicans, Cryputococcus neoformans,
      Trichophyton rubum, Microsporum gypseum, M. canis and Epidermophyton floccosum
      was examined and evaluated by MIC and MFC. The MIC of PBCA-allicin NPs to C.
      albicans (2.93 x 10(-2)mg/ml), T. rubum (1.46 x 10(-2)mg/ml) and E. floccosum
      (1.46 x 10(-2)mg/ml) was significantly lower than that of pure allicin (5.86 x
      10(-2)mg/ml, 2.93 x 10(-2)mg/ml, 2.93 x 10(-2)mg/ml, respectively); accordingly,
      the MFC of PBCA-allicin NPs to C. albicans (5.86 x 10(-2)mg/ml), T. rubum (2.93 x
      10(-2)mg/ml), E. floccosum (2.93 x 10(-2)mg/ml) and M. canis (2.93 x 10(-2)mg/ml)
      also decreased dramatically. These favourable results indicated that pure allicin
      has stronger in vitro anti-fungal efficacy to six tested fungi than alliinase and
      alliin. Moreover, it has improved significantly after pure allicin being wrapped
      into PBCA NP, which may be due to the NP's good prolonged release effect and nano
      scale dimensions.

PMID- 19105899
TI  - Microwave synthesis of poly(L-lactic acid).
AB  - Synthesis of poly(L-lactic acid) typically requires a long process time with the
      use of tin octoate as a catalyst. In this study microwave-assisted polymerization
      of lactic acid has been studied both with the aid and without the aid of tin
      octoate catalyst. While the presence of tin octoate assists in the polymerization
      process, it is not a pre-requisite to polymerization with microwaves. Molecular
      masses in excess of 25 kDa were possible over process times as little as 2.5 h
      without the need for a controlled environment. Fourier-transform infrared
      spectroscopy, proton nuclear magnetic resonance spectroscopy and gel-permeation
      chromatography were used to follow the polymerization process. Microwave-assisted
      polymerization of lactic acid to yield poly(L-lactic acid) has been shown to be a
      viable and quicker alternative to tradition approaches to the synthesis of poly(L
      lactic acid).

PMID- 19105897
TI  - Molecular aspects of mucoadhesive carrier development for drug delivery and
      improved absorption.
AB  - Although the oral route remains the most favored route of drug administration,
      major scientific obstacles prevent the effective and efficient delivery of low
      molecular-mass drugs, peptides and proteins that exhibit poor solubility and
      permeability. Mucoadhesive dosage forms and the associated drug carriers have the
      ability to interact at a molecular level with the mucus gel layer that lines the
      epithelial surfaces of the major absorptive regions of the body. This interaction
      provides an increased residence time of the therapeutic formulation while
      localizing the drug at the site of administration. Such local, non-specific
      targeting leads to an increase in both oral absorption and bioavailability.
      Fundamental understanding of the biological processes encountered along the
      gastrointestinal tract can provide a sufficient engineer of carriers that are
      capable to provide this increase in residence time. Here we discuss the
      theoretical framework for achieving mucoadhesive systems as related to
      biomaterials science and the structure of the biomaterials used.

PMID- 19105901
TI  - Kinetics of in vitro lactoferrin deposition on silicone hydrogel and FDA group II
      and group IV hydrogel contact lens materials.
AB  - The aim of this study was to compare the kinetics of lactoferrin deposition on
      silicone hydrogel (SH) and conventional FDA group II and group IV hydrogel
      contact lens materials. Seven lens materials, two conventional (etafilcon A, FDA
      group IV; omafilcon A, FDA group II) and five SH (lotrafilcon A, lotrafilcon B,
      balafilcon A, galyfilcon A and senofilcon A), were incubated in 1 ml (125)I
      labeled lactoferrin solution for time periods ranging from 1 h to 28 days. At the
      end of specified incubation periods radioactive counts were determined on the
      lenses using an Automatic Gamma Counter. There was a gradual increase in
      lactoferrin deposition on all the lenses across all time points. At the end of 28
      days the amount of lactoferrin/lens in microg was 11.3 +/- 1.9 for etafilcon A,
      6.8 +/- 2.0 for omafilcon A, 2.1 +/- 0.9 for lotrafilcon A, 3.1 +/- 1.0 for
      lotrafilcon B, 11.8 +/- 2.9 for balafilcon A, 5.4 +/- 1.1 for galyfilcon A and
      5.6 +/- 0.6 for senofilcon A. After 28 days, etafilcon A and balafilcon A
      deposited lactoferrin to the greatest degree (P < 0.05), but these were not
      different from each other (P = 0.48), while lotrafilcon A and B deposited the
      least (P < 0.05 vs. other lenses; P = 0.57 with each other). Galyfilcon A,
      senofilcon A and omafilcon A (P < 0.05 compared with other lenses; P > 0.05 with
      each other) deposited intermediate levels of lactoferrin. We concluded that
      radiochemical analysis is a sensitive and effective technique to determine the
      small quantities of lactoferrin deposited on SH lenses. The kinetics of
      lactoferrin deposition on contact lens materials depend on the chemical structure
      of the lens material.

PMID- 19105900
TI  - Matrix modifications modulate ophthalmic drug delivery from photo-cross-linked
      poly(propylene fumarate)-based networks.
AB  - In this work, different modifications of photo-cross-linked poly(propylene
      fumarate)/poly(N-vinyl pyrrolidone) (PPF/PNVP) matrices were studied for their
      effect on the release kinetics of two ophthalmic drugs. The hydrophilicity of
      solid PPF/PNVP matrices loaded with acetazolamide (AZ) or timolol maleate (TM)
      was increased by adding various amounts of poly(ethylene glycol) (PEG) or by
      increasing the amount of N-vinyl pyrrolidone (NVP) in the polymer mixture prior
      to cross-linking. The in vitro release studies that utilized high-performance
      liquid chromatography for quantification revealed highly accelerated drug release
      from the matrices with increasing contents of the hydrophilic modifier. AZ was
      released from matrices containing 5% PEG in 56 days, which equals approximately
      25% of the release period found for the unmodified matrices. A comparable
      acceleration in drug release was found for TM-loaded samples modified with 5%
      PEG. These studies further revealed that 1% PEG is sufficient to shorten the TM
      release duration by one-third. A significant acceleration in drug release was
      also found for the samples that were fabricated from a PPF-NVP mixture with
      increased NVP content. Matrix water content and erosion were assessed
      gravimetrically. Micro-computed tomography was used to image structural changes
      of the release systems and shed light on the drug-release mechanism. This study
      showed that hydrophilic matrix modifications of PPF/PNVP matrices accelerate the
      drug release of two ophthalmic drugs and represent a suitable tool to adjust drug
      release rates from PPF-based matrices for different therapeutic needs.

PMID- 19105902
TI  - Uptake of enzymatically-digested hyaluronan by liver endothelial cells in vivo
      and in vitro.
AB  - Intravenously-injected hyaluronan (HA) is distributed into liver in which
      endothelium is a site of uptake and degradation of HA. The role and fate of HA
      have been widely investigated; however, effects of size and dose of HA on its
      metabolism have not been well documented yet. To investigate these effects, we
      prepared fluorescein-labeled HAs, according to the modified methods described by
      de Belder and Wik, which were enzymatically digested. The 90 kDa fluorescein
      labeled HA gradually accumulated in a liver that was distributed into the
      endothelium; however, 10 kDa or less HA did not. Cell fractionation and flow
      cytometry further demonstrated the cell of uptake in the liver is an endothelial
      cell, both in vivo and in vitro. Interestingly, the largest uptake by liver
      endothelial cells in vitro was observed in 10 kDa HA, even though which did not
      accumulate in liver in vivo. These results suggest that the result observed with
      10 kDa HA in vivo is due to the rapid excretion in urine. Thus, inhibiting of the
      digestion or suppressing of the urinary excretion would enhance uptake of HA in
      vivo. These ideas may help to deliver drugs or genes targeting to liver
      endothelium.

PMID- 19105903
TI  - Preparation and hydrolytic degradation of poly(hexylene terephthalate-co-lactide)
      co-polyesters from melting polycondensation.
AB  - To obtain a biodegradable polymer material with satisfactory thermal properties,
      higher elongation and modulus of elasticity, a series of biodegradable
      aliphatic/aromatic co-polyesters, poly(hexylene terephthalate-co-lactide) (PHTL),
      was synthesized via melt polycondensation from dimethyl terephthalate (DMT), 1,6
      hexanediol (HDO) and oligo(lactic acid) (OLA) in the presence of titanium (IV)
      butoxide. The resulting co-polyesters were characterized by proton nuclear
      magnetic resonance ((1)H-NMR), differential scanning calorimetry,
      thermogravimetry and wide-angle X-ray scattering, and their melting temperature,
      melting heat of fusion, glass-transition temperature (T(g)) and thermal
      decomposition temperature (T(m)) (1.5 wt%) were obtained. Only one T(g) and two
      T(m) values were observed for all samples, and were found to decrease gradually
      with increase of lactide moieties. By using the relative integral areas of the
      dyad peaks in the (1)H-NMR spectrum of co-polyesters PHTL, the sequence lengths
      of the hexylene terephthalate (n(HT)) units in the resultant co-polyesters are
      3.5. The PHTL co-polyesters exhibited a pronounced hydrolytic degradability,
      which increase with the content in lactide units. (1)H-NMR analysis of the
      residue left by evaporation of the mother solution after hydrolytic degradation
      revealed that the degradation products consisted mostly of lactide and hexylene
      terephthalate blocks.

PMID- 19105904
TI  - Novel quaternized chitosan and polymeric micelles with cross-linked ionic cores
      for prolonged release of minocycline.
AB  - Novel multifunctional octadecyl quaternized carboxymethyl chitosans (OQCMCs) with
      varying degree of quaternary substitution (DS) and molecular mass were prepared
      and compared with quaternized chitosan. OQCMCs exhibited excellent solubility
      both in water and organic solvents. Nanoparticles of OQCMCs offered many
      advantages, such as easier fabrication and modulation of their size and degree of
      positive charge, and a lower cytotoxic effect compared with PEI (25 kDa). DNA can
      be successfully adsorbed on its surface. Electrostatic attraction of
      carboxymethyl and quaternary groups in OQCMCs was utilized as micellar template
      for the synthesis of cross-linked micelles. Formation and characteristics of
      OQCMC polymeric micelles were studied by fluorescence spectroscopy, tensiometry,
      SEM, TEM and particle size analysis. Self-assembled OQCMC micelles were evaluated
      as carrier of the lipophilic drug, minocycline hydrochloride (MH). MH was
      incorporated into cross-linked ionic cores of micelles with remarkably high
      efficiency (22.7%, w/w). MH-loaded OQCMC polymeric micelles exhibited a slow
      steady release profile over a 1-week period at 37 degrees C. The OQCMC micelles
      are potentially useful for gene and lipophilic drug delivery applications.

PMID- 19105905
TI  - A novel surface modification using tissue factor reconstituted in phospholipid
      vesicles for the activation of blood coagulation.
AB  - We describe a novel method to immobilize recombinant human tissue factor (rhTF)
      reconstituted in phospholipid vesicles. The rhTF vesicles were immobilized in a
      multilayer vesicle structure using cholesterol-DNA tethers spontaneously inserted
      into the lipid membrane. The properties of the rhTF vesicle surface modification
      were characterized by surface plasmon resonance biosensor technology. As an
      application of this surface modification, we investigated its use as a blood
      coagulation activating surface. The coagulation activating capacity of the
      surface modification was tested by exposure to human whole blood in a flow
      chamber. No increase in rhTF levels in the blood was found after passage through
      the flow chamber, indicating that the rhTF surface modification was stable.
      Thrombin-antithrombin (TAT) and prothrombin fragment (PF) 1 + 2 levels increased
      after exposure to the surface, and decreased in a concentration-dependent way
      upon addition of melagatran (a direct thrombin inhibitor), i.e., coagulation
      activity triggered by rhTF could be suppressed by anticoagulation. The results
      with this new thrombogenic surface are promising, and will be further developed
      into a useful tool for coagulation related investigations, e.g., characterization
      of anticoagulants and biomaterials.

PMID- 19105906
TI  - Economic influences on GPs' decisions to provide out-of-hours care.
AB  - BACKGROUND: Introduction of the new general medical services contract offered UK
      general practices the option to discontinue providing out-of-hours (OOH) care.
      This aimed to improve GP recruitment and retention by offering a better work-life
      balance, but put primary care organisations under pressure to ensure sustainable
      delivery of these services. Many organisations arranged this by re-purchasing
      provision from individual GPs. AIM: To analyse which factors influence an
      individual GP's decision to re-provide OOH care when their practice has opted
      out. DESIGN OF STUDY: Cross-sectional questionnaire survey. SETTING: Rural and
      urban general practices in Scotland, UK. METHOD: A postal survey was sent to all
      GPs working in Scotland in 2006, with analyses weighted for differential response
      rates. Analysis included logistic regression of individuals' decisions to re
      provide OOH care based on personal characteristics, work and non-work time
      commitments, income from other sources, and contracting primary care
      organisation. RESULTS: Of the 1707 GPs in Scotland whose practice had opted out,
      40.6% participated in OOH provision. Participation rates of GPs within primary
      care organisations varied from 16.7% to 74.7%. Males with young children were
      substantially more likely to participate than males without children (odds ratio
      [OR] 2.44, 95% confidence interval [CI] = 1.36 to 4.40). GPs with higher-earning
      spouses were less likely to participate. This effect was reinforced if GPs had
      spouses who were also GPs (OR 0.52, 95% CI = 0.37 to 0.74). GPs with training
      responsibilities (OR 1.36, 95% CI = 1.09 to 1.71) and other medical posts (OR
      1.38, 95% CI = 1.09 to 1.75) were more likely to re-provide OOH services.
      CONCLUSION: The opportunity to opt out of OOH care has provided flexibility for
      GPs to raise additional income, although primary care organisations vary in the
      extent to which they offer these opportunities. Examining intrinsic motivation is
      an area for future study.

PMID- 19105908
TI  - Out-of-hours care: remuneration alone is no panacea.

PMID- 19105910
TI  - Nurse practitioner management of acute in-hours home visit or assessment
      requests: a pilot study.
AB  - BACKGROUND: GPs often perceive home-visit requests as a time-consuming aspect of
      general practice. The new general medical services contract provides for
      practices to be relieved of responsibility for home-visits, although there is no
      model for the transfer of care. One such model could be to employ nurse
      practitioners to manage such requests. Nurse practitioners can effectively
      substitute for GPs in managing same-day in-hours emergency care in the surgery,
      but their role in managing all such requests, including those requiring home
      visits, has not been assessed. AIM: To explore the feasibility and clinical
      management outcomes of nurse practitioner management of same-day care requests,
      including those requiring home visits, to inform a proposed randomised controlled
      trial. DESIGN OF STUDY: Non-randomised comparative trial. SETTING: One large
      general practice (14 600 patients) in south London. METHOD: Nurse practitioner
      assessment and management of all same-day care requests for 2 days per week was
      compared with normal GP management on another 2 days, over a 6-month period.
      Clinical management outcome data were collected from patient records and from
      data-collection forms completed by a nurse practitioner and GPs. Patient and
      staff satisfaction was assessed by questionnaire. RESULTS: The nurse practitioner
      was more likely than GPs to assess patients in person, less likely to give advice
      alone, and more likely to issue a prescription. There was no significant
      difference between the nurse practitioner and GPs regarding any other clinical
      management outcomes or patient satisfaction; however, the response rate of the
      patient satisfaction questionnaire in this pilot study was poor. CONCLUSION:
      Nurse practitioner management of acute in-hours care requests, including home
      visits, appears feasible in practice and merits further assessment.

PMID- 19105909
TI  - The contraceptive revolution: some excellent progress but work still to be done.

PMID- 19105911
TI  - Users' reports and evaluations of out-of-hours health care and the UK national
      quality requirements: a cross sectional study.
AB  - BACKGROUND: National standards for delivery of out-of-hours services have been
      refined. Health service users' preferences, reports, and evaluations of care are
      of importance in a service that aims to be responsive to their needs. AIM: To
      investigate NHS service users' reports and evaluations of out-of-hours care in
      the light of UK national service quality requirements. DESIGN: Cross sectional
      survey. SETTING: Three areas (Devon, Cornwall, Sheffield) of England, UK. METHOD:
      Participants were 1249 recent users of UK out-of-hours medical services. Main
      outcome measures were: users' reports and evaluations of out-of-hours services in
      respect of the time waiting for their telephone call to the service to be
      answered; the length of time from the end of the initial call to the start of
      definitive clinical assessment ('call back time'); the time waiting for a home
      visit; and the waiting time at a treatment centre. RESULTS: UK national quality
      requirements were reported as being met by two-thirds of responders. Even when
      responders reported that they had received the most rapid response option for
      home visiting (waiting time of 'up to an hour'), only one-third of users reported
      this as 'excellent'. Adverse evaluations of care were consistently related to
      delays encountered in receiving care and (for two out of four measures) sex of
      patient. For 50% of users to evaluate their care as 'excellent', this would
      require calls to be answered within 30 seconds, call-back within 20 minutes, time
      spent waiting for home visits of significantly less than 1 hour, and treatment
      centre waiting times of less than 20 minutes. CONCLUSION: Users have high
      expectations of UK out-of-hours healthcare services. Service provision that meets
      nationally designated targets is currently judged as being of 'good' quality by
      service users. Attaining 'excellent' levels of service provision would prove
      challenging, and potentially costly. Delivering services that result in high
      levels of user satisfaction with care needs to take account of users'
      expectations as well as their experience of care.

PMID- 19105912
TI  - Risk taking in general practice: GP out-of-hours referrals to hospital.
AB  - BACKGROUND: Emergency admissions to hospital at night and weekends are
      distressing for patients and disruptive for hospitals. Many of these admissions
      result from referrals from GP out-of-hours (OOH) providers. AIM: To compare rates
      of referral to hospital for doctors working OOH before and after the new general
      medical services contract was introduced in Bristol in 2005; to explore the
      attitudes of GPs to referral to hospital OOH; and to develop an understanding of
      the factors that influence GPs when they refer patients to hospital. DESIGN OF
      STUDY: Cross-sectional comparison of admission rates; postal survey. SETTING:
      Three OOH providers in south-west England. METHOD: Referral rates were compared
      for 234 GPs working OOH, and questionnaires explored their attitudes to risk.
      RESULTS: There was no change in referral rates after the change in contract or in
      the greater than fourfold variation between those with the lowest and highest
      referral rates found previously. Female GPs made fewer home visits and had a
      higher referral rate for patients seen at home. One-hundred and fifty GPs
      responded to the survey. Logistic regression of three combined survey risk items,
      sex, and place of visit showed that GPs with low 'tolerance of risk' scores were
      more likely to be high referrers to hospital (P<0.001). CONCLUSION: GPs'
      threshold of risk is important for explaining variations in referral to hospital.

PMID- 19105913
TI  - Patients' ideas, concerns, and expectations (ICE) in general practice: impact on
      prescribing.
AB  - BACKGROUND: Although studies are available on patients' ideas, concerns, and
      expectations in primary care, there is a scarcity of studies that explore the
      triad of ideas, concerns, and expectations (ICE) in general practice
      consultations and the impact on medication prescribing. AIM: To evaluate the
      presence of ICE and its relation to medication prescription. DESIGN OF STUDY:
      Cross-sectional study. SETTING: Thirty-six GP teaching practices affiliated with
      the University of Ghent, in Flanders, Belgium. METHOD: Participants were all
      patients consulting on 30 May 2005, and their doctors. Reasons for an encounter
      (consultation or home visit) with new and follow-up contacts, the identification
      of ICE, and the prescription of medication were recorded by 36 trainee GPs
      undergoing observational training. The study included 613 consultations. RESULTS:
      One, two, or three of the ICE components were expressed in 38.5%, 24.4%, and
      20.1% (n = 236, 150, 123) of contacts respectively. On the other hand, in 17.0%
      (104/613) of all contacts, and in 22% (77/350) of the new contact reasons, no ICE
      was voiced, and the GPs operated without knowing this information about the
      patients. Mean number of ICE components per doctor and per contact was 1.54
      (standard deviation = 0.54). A logistic regression analysis of the 350 new
      contacts showed that the presence of concerns (P = 0.037, odds ratio [OR] 1.73,
      95% confidence interval [CI] = 1.03 to 2.9), and expectations (P = 0.009, OR =
      2.0, 95% CI = 1.2 to 3.4) was associated with not prescribing new medication
      (dichotomised into the categories present/absent); however, other patient,
      doctor, and student variables were not significantly associated with medication
      prescription. CONCLUSION: An association was found between the presence of
      concerns and/or expectations, and less medication prescribing. The data suggest
      that exploring ICE components may lead to fewer new medication prescriptions.

PMID- 19105914
TI  - Preventive advice given by patients with type 2 diabetes to their offspring.
AB  - BACKGROUND: Patients' advice-giving behaviour could be a useful preventive
      strategy for type 2 diabetes. AIM: To investigate the conditions under which
      patients offer advice to their offspring and to assess the factors that
      facilitate advice giving. DESIGN OF STUDY: Cross-sectional observational study.
      SETTING: A general hospital with a diabetes clinic in a metropolitan suburb in
      Japan. METHOD: Parents with type 2 diabetes (n = 221) who had offspring aged 20
      49 years inclusive without diabetes completed a self-administered questionnaire
      containing items relating to advice-giving behaviour, demographic
      characteristics, risk perception, and their disease status. RESULTS: A total of
      184 (83.3%) patients responded that parental advice-giving behaviour is needed
      for their offspring, while 138 (62.4%) actually advised their offspring. Multiple
      logistic regression analysis showed that patients who were female (odds ratio
      [OR] = 1.94, 95% confidence interval [CI] = 1.03 to 3.65, P = 0.041), living with
      their offspring (OR =1.92, 95% CI = 1.04 to 3.57, P = 0.038), had complications
      (OR = 2.74, 95% CI = 1.25 to 6.00, P = 0.029), or perceived that their offspring
      had a high risk of developing diabetes (OR =1.45, 95% CI = 1.09 to 1.93, P =
      0.011) were most likely to advise their offspring. CONCLUSION: Patients with type
      2 diabetes recognised the need to give advice about preventive behaviour to their
      offspring but were not necessarily engaging in advice-giving behaviour. Advice
      giving behaviour was affected by the parents' own disease status, their
      perception of their offspring's risk of developing diabetes, and the relationship
      between the patients and their offspring.

PMID- 19105915
TI  - Randomised controlled trial of intensive multifactorial treatment for
      cardiovascular risk in patients with screen-detected type 2 diabetes: 1-year data
      from the ADDITION Netherlands study.
AB  - BACKGROUND: A growing body of evidence suggests that earlier diagnosis and
      treatment of diabetes may be beneficial; however, definitive evidence is lacking.
      AIM: To evaluate the effectiveness of an intensified multifactorial treatment on
      cardiovascular risk factors in patients with screen-detected type 2 diabetes.
      DESIGN OF STUDY: Randomised controlled trial. SETTING: Seventy-nine general
      practices in the southwestern region of the Netherlands. METHOD: In this
      randomised trial, patients diagnosed with diabetes by screen-detection were
      assigned to intensified (n = 255) or routine treatment (n = 243), and followed
      over 1 year. Intensified treatment consisted of pharmacological treatment
      combined with lifestyle education to achieve haemoglobin A1c (HbA1c) <7.0%, blood
      pressure <135/85 mmHg, and cholesterol <5.0 mmol/l (4.5 mmol/l if cardiovascular
      disease was present). Health-related quality of life (HRQoL) was assessed using
      the Short Form (SF)-36. Analyses were performed using generalised estimating
      equations models. RESULTS: Changes in body mass index were 0.2 (routine care)
      versus -1.4 kg/m(2) (intensified treatment), P<0.001; systolic blood pressure -19
      versus -33 mmHg, P<0.001; diastolic blood pressure -7 versus -12 mmHg, P<0.001;
      HbA1c -0.9% versus -1.1%, P = 0.03; cholesterol -0.5 versus -1.2 mmol/l, P<0.001;
      high-density lipoprotein cholesterol 0.1 versus 0.1 mmol/l, P = 0.26; low-density
      lipoprotein cholesterol -0.5 versus -1.0 mmol/l, P<0.001; triglycerides -0.3
      versus -0.4 mmol/l, P = 0.71. No difference in HRQoL between the two groups was
      reported. CONCLUSION: Intensified multifactorial treatment of patients with
      screen-detected diabetes in general practice reduces cardiovascular risk factor
      levels significantly without worsening HRQoL.

PMID- 19105916
TI  - Hypoglycaemia in residential care homes.
AB  - Hypoglycaemia is the most common metabolic complication occurring in older people
      with type 2 diabetes. Limited data are available about prevalence of diabetes or
      its complications in care homes. However, the prevalence of residents with
      diabetes in care homes seems to be significant. There is high level of
      disability, dependency, and polypharmacy among residents in these settings.
      Hypoglycaemia is both an important adverse reaction of treatment and an outcome
      measure. This study reviews the relevant literature and reports a case of
      hypoglycaemia to demonstrate the causes of hypoglycaemia, characteristics of
      these patients, and the complexity of their problems.

PMID- 19105917
TI  - Depression and musculoskeletal problems.

PMID- 19105918
TI  - The end of practice-based research?

PMID- 19105921
TI  - Health for all? Dream on!

PMID- 19105922
TI  - Boundary issues: employing patients as staff?

PMID- 19105924
TI  - A consideration of the qualities of a 'good' doctor with some help from the
      humanities.

PMID- 19105926
TI  - Twenty years of the 'face' model: memorial to Henry Middleton.

PMID- 19105928
TI  - [Five years follow-up of 220 chronic HBV carriers].
AB  - OBJECTIVES: To understand the hepatic pathology, hepatitis B reactivation rates
      and serological changes in chronic HBV carriers. METHODS: A 5 year dynamic
      observation and survey of 220 chronic HBV carriers in Wuxi district was taken,
      analyzing their clinical symptoms, liver histopathology, virology and HBV
      immunological markers. RESULTS: Thirty-five of the 220 (15.9%) patients, showed
      hepatitis B reactivation. The hepatitis B reactivation rate of patients with
      obvious hepatic tissue inflammation (> or = G2) was 27.0% (33/122) and the rate
      of the patients with mild hepatic tissue inflammation (G0-G1) was 2.0% (2/98),
      showing significant differences (x2=25.41, P less than 0.01). The reactivation
      rate of patients with high inflammation was clearly higher than those with mild
      inflammation. Twenty-seven of the 35 hepatitis B reactivation cases were older
      than 40 years, showing a significant association between the ages of the patients
      and hepatitis B reactivation rates (x2=6.72, P less than 0.01), moreover there
      was no relationship between sex and the hepatitis B reactivation rate. There were
      differences in the inflammation grades and fibrosis stages between HBeAg positive
      and anti-HBe positive group cases (Kruskal-Wallis Test, x2=8.68, P less than
      0.01, x2=6.84, P less than 0.01), showing inflammation grades and fibrosis stages
      of the anti-HBe positive group were higher than those of the HBeAg positive
      group. There were no obvious differences about the inflammation grade between age
      less than 40 years old and > or = 40 years old group cases (x2=0.62, P more than
      0.05), but there were significant statistical differences about the fibrosis
      stage (x2=7.37, P less than 0.01), showing fibrosis stage of more than 40 years
      old group cases was clearly higher than the less than 40 years old group cases.
      Fifty-six cases received a liver biopsy for a second time and 23 for a third
      time. We found those whose hepatic tissues were normal in their first liver
      biopsies, then their liver histology continued remaining stable for several years
      while those with abnormal ones hardly or only recovered slightly. The rate of
      HBsAg turning to negativity per year was 1.55% and for HBeAg was 5.4%.
      CONCLUSION: The hepatic tissue pathology for most chronic HBV carriers (55%) had
      significant abnormalities (inflammation grade > or = G2), and the rates of
      hepatitis B reactivation were highly relevant to the liver inflammation grades
      and the ages of the patients.

PMID- 19105929
TI  - [The effect of telbivudine on peripheral blood CD4+CD25+ regulatory T cells and
      its significance in patients with chronic hepatitis B].
AB  - OBJECTIVE: To investigate the effect of telbivudine on peripheral blood
      regulatory T cells and its significance in patients with chronic hepatitis B
      (CHB). METHODS: Thirty-six HbeAg positive chronic hepatitis B patients were
      recruited and received telbivudine treatment for 9 months. Before and during the
      3, 6, 9 months of treatment, flow cytometry was used to detect the proportion of
      peripheral blood Tregs; real-time PCR was used to detect the levels of HBV DNA in
      the serum. Markers of hepatitis B virus infection were detected by ELISA assay
      and levels of alanine aminotransferase in the serum were measured. RESULTS: The
      proportion of peripheral blood Tregs in patients with CHB was significantly
      higher than that in healthy controls and decreased over 6 or 9 months of
      telbivudine treatment to a level comparable to that of the healthy controls.
      After 3 months of telbivudine treatment, the rate of undetectable HBV DNA in
      patients whose proportion of peripheral blood Tregs was decreased was higher than
      those whose Tregs had been reduced, but the difference was not statistically
      significant (P more than 0.05). Three, 6 or 9 months of telbivudine treatment
      resulted in HbeAg negativity in 4 (11.1%) patients, 7 (19.4%) patients or 9
      (25.0%) patients respectively. In 7 (19.4%) patients who had seroconversion from
      HBeAg to anti-HBeAg, after 3 or 6 months of telbivudine treatment, their
      proportion of peripheral blood Tregs had decreased to a level comparable to that
      of the healthy controls. CONCLUSION: Telbivudine treatment reduces HBV
      replication and the proportion of peripheral blood Tregs. In addition, patients
      who have their proportion of peripheral blood Tregs decreased quickly at the
      early phase of telbivudine treatment are prone to have HBeAg to anti-HBeAg
      seroconversion.

PMID- 19105930
TI  - [Correlation of polymorphisms of interleukin-2 gene and HBV DNA copies in
      patients with chronic hepatitis B].
AB  - OBJECTIVE: To investigate the relationships of polymorphisms of interleukin-2 (IL
      2) gene to the susceptibility of chronic hepatitis B, and to analyze the
      frequencies of IL-2 gene polymorphisms and the HBV-DNA copies in patients with
      chronic hepatitis B. METHODS: Two single nucleotide polymorphisms of IL-2 gene
      promoter -385T/G and +114T/G at exon one were analyzed in 155 patients with
      chronic hepatitis B and in 170 age- and sex-matched controls from a Chinese
      population. Polymerase chain reaction-restriction fragment length polymorphism
      (PCR-RFLP) strategy and DNA sequencing were used, and the serum HBV DNA in these
      patients was determined by real-time PCR. RESULTS: There were no differences in
      the distributions of IL-2 gene +114T/G polymorphism in the patient group and the
      controls, but their IL-2 gene -385T/G polymorphisms were significantly different
      (P less than 0.05). The relative risk of being chronic hepatitis B victims with T
      allele was 1.490 times of those with G allele (OR=1.490, 95% CI: 1.085-2.046).
      The association between the genotype of IL-2 gene polymorphisms and HBV-DNA
      copies showed that the frequency of -385G allele carriers in high HBV-DNA copy
      group was closer than that in low HBV-DNA copy group (chi2=6.051, P=0.014).
      CONCLUSIONS: IL-2 gene -385T/G polymorphism is associated with chronic hepatitis
      B and G allele is an important genetic susceptibility gene for chronic hepatitis
      B. In IL-2 gene -385G allele carriers the risk of increasing HBV-DNA copies may
      be related to the pathogenesis of chronic hepatitis B.

PMID- 19105931
TI  - [Quantitive changes of circulating myeloid and plasmacytoid dendritic cell
      subsets in HBV infected patients during different periods of their infection].
AB  - OBJECTIVE: To study the quantities of myeloid and plasmacytoid dendritic cell
      (mDC, pDC) subsets associated with different blood virus loads (HBV DNA) in
      patients in different periods of HBV infection (immune tolerance, immune
      activities and non-replicating periods). METHODS: Thirty HBV infected patients in
      different stages of infection were enrolled. They were divided into three groups:
      an immune tolerance group (10 cases), an immunization activities group (10
      cases), and a non-replication group (10 cases). Ten healthy people were enrolled
      and served as controls. Blood (10 ml) from the patients and the controls were
      collected and the numbers of dendritic cells (DC) in percentage were counted
      using flow cytometry. The numbers of mDC and pDC were counted and the relevance
      of them with their blood virus loads (HBV DNA) was analyzed using statistical
      methods. RESULTS: (1) Absolute values of mDC, pDC percentage and pDC absolute
      value of the HBV infected patients were lower than those of the healthy control
      group (P less than 0.05). mDC percentage of the HBV infected patients was a
      little lower than that of the healthy controls but of no statistical significance
      (P more than 0.05). (2) The percentage of mDC in the healthy controls was higher
      than that in the tolerance group (P less than 0.05) and its absolute value in the
      healthy control group was higher than those in the immune tolerance group and the
      immune activities group (P less than 0.05). pDC percentage of the healthy control
      group was higher than those of the immune activities and non-reproduction groups
      (P less than 0.05). pDC absolute value of the healthy control group was higher
      than those of the immune tolerance, immune activities and non-reproduction groups
      (P less than 0.05). (3) The pDC counts in the tolerance group were negatively
      correlated with HBV DNA levels (r = -0.686, P less than 0.05). CONCLUSIONS: (1)
      DC frequency and counts of HBV infected patients in different periods decreased.
      The immune active group decreased significantly more than the healthy control
      group (P less than 0.05). (2) pDC counts show a negative correlation with HBV DNA
      levels in only the tolerance group.

PMID- 19105932
TI  - [FibroTest-ActiTest for predicting liver fibrosis and inflammatory activity in
      Chinese patients with chronic hepatitis B].
AB  - OBJECTIVE: To confirm the diagnostic value of FibroTest-ActiTest (FT-AT) in
      predicting liver fibrosis and inflammatory activity in patients with chronic
      hepatitis B (CHB), and to study the discordances between FT and their liver
      biopsies. METHODS: A study was performed on 100 patients with CHB who underwent
      liver biopsies in our hospital. Serum samples for biochemical markers were taken
      on the day of their biopsies. Diagnostic accuracies were assessed by ROC curve
      analysis. RESULTS: The median biopsy specimen size was 15 mm (range: 8-30), with
      9 (median) portal tracts (range 5-26). Thirty-nine patients were classified as
      Ishak F3-F6 in fibrosis and 65 patients as A2-A4 in inflammation. Areas under ROC
      curve for diagnosis of significant inflammation (A2-A4), significant fibrosis (F3
      F6), and cirrhosis (F5-F6) were 0.833 (95% CI: 0.753-0.913), 0.840 (0.750-0.929),
      and 0.862 (0.721-1.003), respectively. FT less than 0.31 had a NPV of 86% for
      excluding significant fibrosis, whereas FT > or = 0.72 had a PPV of 92% for
      predicting significant fibrosis. Among the 26 patients with 2 fibrosis stages of
      discordances between FT and biopsy, the discordance was attributable to biopsy in
      3 cases, to FT in 7, and undetermined in 16. CONCLUSION: This study confirms the
      diagnostic value of FT-AT and suggests that 68% of our patients with CHB can be
      reliably identified by FT without a liver biopsy and with a diagnosis accuracy of
      87%.

PMID- 19105933
TI  - [Growth factors may enhance c-fos and c-jun gene expressions of hepatic stellate
      cells].
AB  - OBJECTIVE: To investigate the effects of growth factors on c-fos and c-jun gene
      expressions in hepatic stellate cells. METHODS: Hepatic stellate cell (HSC) T6
      was cultured in media containing different concentrations of platelet derived
      growth factor (PDGF) (8 ng/ml, 40 ng/ml or 200 ng/ml) and transforming growth
      factor (TGF) beta (0.2 ng/ml, 1 ng/ml or 5 ng/ml) and the cells were collected at
      different incubation periods (8, 24, 48 or 72 h). Total RNA of the HSC was
      isolated and c-fos and c-jun gene expression levels were measured by reverse
      transcription polymerase chain reaction. RESULTS: C-fos gene expression levels of
      the HSC cultured in low (8 ng/ml), medium (40 ng/ml) and high (200 ng/ml)
      concentrations of PDGF were all much higher than those of the control group after
      exposure to PDGF at 8, 24, 48 or 72 h. The c-fos gene expression levels of the
      HSC increased as the dosage of PDGF increased and there were significant
      differences of c-fos gene expression among the three PDGF groups. C-jun gene
      expression levels of the HSC in low (0.2 ng/ml), medium (1.0 ng/ml) and high (5.0
      ng/ml) concentrations of TGF beta groups were much higher than those of the
      control group after exposure to TGF beta at 8, 24, 48 or 72 h. The c-jun gene
      expression levels of the HSC increased as the dosage of TGF beta increased and
      there were significant differences of c-jun gene expression among the three TGF
      beta groups. CONCLUSION: PDGF and TGF beta can strongly up-regulate c-fos and c
      jun gene expressions in hepatic stellate T6 cells.

PMID- 19105934
TI  - [Application of 3.0T MRI 3D-VIBE dynamic contrast-enhanced in the diagnosis of
      small hepatocellular carcinomas].
AB  - OBJECTIVES: To investigate the detection rate of small hepatocellular carcinomas
      using 3.0T MRI 3D-volumetric interpolated breath-hold examination (VIBE) sequence
      dynamic contrast-enhanced scan, and to evaluate its application in the diagnosis
      of small hepatocellular carcinomas. METHODS: Imaging data of 61 cases of small
      hepatocellular carcinomas obtained using a 3.0 T Siemens Magnetom Trio Tim
      magnetic resonance scanner for plain scan and multi-phase dynamic contrast
      enhanced scans of three-dimensional volumetric interpolated breath-hold
      examination (3D-VIBE) were retrospectively analyzed with reference to their
      pathological diagnoses. The signal and enhanced features and the detection rates
      of the tumors in different phases of examination were analyzed. RESULTS: Sixty
      six lesions were detected in the livers of the 61 patients by pathological
      examinations, of which 49 had pseudocapsule formation. In their T1WI plain
      scanning, 43 (65.15%) lesions were found, of which pseudocapsules were found in
      19 (38.78%). In their T2WI imaging, 53 (80.30%) lesions were found. In dynamic
      enhanced 3D-VIBE sequence, 65 (98.48%) lesions were found, of which 35 (71.43%)
      were found with pseudocapsules. The sizes of the carcinomas ranged from 0.8 to
      3.0 cm, 2.1cm on the average. The results of statistical analysis for the
      detection rates of the cancers of the three different sequences were
      significantly different (chi2=24.197, P less than 0.05). The differences of
      qualitative accuracy obtained by plain scan (T1WI + T2WI) and 3D-VIBE sequence
      were significantly different (chi2=66, P less than 0.05). CONCLUSION: 3.0 T MRI
      3D-VIBE sequence dynamic contrast-enhanced scan is high-speed and can clearly
      demonstrate the arterial phase, the portal venous phase and the parenchymal phase
      images. It not only can find small lesions which can not be found with a plain
      scan, but also can assist diagnosis through a time-intensity curve. It is of
      great value for detection and differential diagnosis of small hepatocellular
      carcinomas.

PMID- 19105935
TI  - [A study on the apoptosis of hepatoma cells synergistically induced by plasmid
      mediated anti-angiogenesis and immunopotentiation therapy].
AB  - OBJECTIVE: To study the effect and mechanism of apoptosis of implanted hepatoma
      cells in mice induced by eukaryotic plasmid-mediated anti-angiogenesis and
      immunopotentiation therapy. METHODS: Mouse endostatin eukaryotic plasmid (pSecES)
      and mouse IL-12 (interleukin 12) eukaryotic plasmid (pmIL-12) were extracted and
      purified from E.coli. H22 hepatoma cells were inoculated into the leg muscles of
      32 mice. The mice were divided into four groups with pSecES, pmIL-12, pSecES+pmIL
      12 and pcDNA3.1 naked plasmid DNA injected into the tumor cell implantation sites
      of each group. Tumor formation and their weights were evaluated. Microvessel
      density, numbers of the infiltrating lymphocytes in the tumors and the apoptosis
      of tumor cells were assayed by microscopical examination of the CD31 and HE
      stained slides of the tumors and TUNEL assay. RESULTS: The tumors of those with
      pSecES or pmIL-12 injections grew slower and with less microvessel density, more
      lymphocyte infiltration and with more apoptosis tumor cells compared with those
      with pcDNA3.1 injections. There was much more tumor cell apoptosis in the
      pSecES+pmIL-12 group (19.9+/-5.5 per 400x microscope field, P less than 0.05)
      than that in any other single plasmid injection group (400x microscopic field:
      pSecES 11.3+/-4.1, pmIL-12 14.6+/-3.2, pcDNA3.1 1.4+/-1.3). CONCLUSIONS: Tumor
      cell apoptosis of the implanted hepatoma in mice can be induced by eukaryotic
      plasmid-mediated anti-angiogenesis and immunotherapy through inhibiting tumor
      angiogenesis and promoting tumor lymphocyte infiltration, by which the growth of
      the implanted hepatoma was inhibited.

PMID- 19105936
TI  - [Effect of sFRP2 on the biological behavior of HepG2 cells].
AB  - OBJECTIVE: To investigate the effect of sFRP2 on the biological behavior of human
      hepatoma carcinoma HepG2 cells. METHODS: HepG2 cells were infected with
      recombinant adenovirus containing mouse sFRP2 gene, and then the proliferation,
      cell cycle distribution, expression of tumor metastasis related factors (CD44,
      CD82/KAI1, EMMPRIN) and beta-catenin protein, and migration ability of the cells
      were detected by MTT, FCM, immunohistochemistry, Western blot and Transwell
      inserts, respectively. RESULTS: sFRP2 protein inhibited the proliferation of
      HepG2 cells, and increased the percentage of G0/G1 period cells. Expression of
      CD44 and CD82/KAI1 proteins, which could inhibit invasion and metastasis of tumor
      cells, was upregulated. However, EMMPRIN protein, which could promote the above
      properties of tumor cells decreased in HepG2 cells infected with the recombinant
      adenovirus containing mouse sFRP-2 gene. Western blot demonstrated that beta
      catenin was expressed in HepG2 cells and there was no significant difference
      between the treated and the control groups. Transwell insert test showed sFRP2
      protein decreased the migration ability of HepG2 cells. CONCLUSION: The
      recombinant adenovirus containing mouse sFRP-2 gene could infect HepG2 cells.
      sFRP2 protein could significantly reduce the capability of proliferation,
      invasion and metastasis of HepG2 cells.

PMID- 19105937
TI  - [Inhibition effect of MIF antibody on the growth of hepatocellular carcinoma cell
      HepG2 in vitro].
AB  - OBJECTIVES: To investigate the inhibitory effect of macrophage migration
      inhibitory factor (MIF) antibody on the proliferation of HepG-2 cells and its
      mechanism. METHODS: HepG-2 cells were stimulated by different concentrations of
      MIF antibody (50, 100, 200 and 400 microg/L). The cell survival rates were
      evaluated by MTT assay. The cell cycles were assessed by flow cytometry (FCM)
      analysis. Cyclin D1 protein expression was examined by immunohistochemical
      methods. Vascular endothelial growth factor (VEGF) protein expression was
      examined by Western blot. ELISA was applied to detect the influence of MIF
      antibody on the production of IL-6 of HepG-2 cells. RESULTS: HepG-2 cells were
      inhibited by MIF antibody in a dose and time dependent manner. FCM analysis
      showed the cell cycles of HepG-2 cells were blocked at G0/G1 phase. With
      concentrations of MIF antibody of 0, 50, 100, 200, 400 microg/L, the percentages
      of cells in G0/G1 phase at 48 h were 61.34%+/-1.08%, 65.08%+/-2.71%, 71.19%+/
      1.19%, 78.39%+/-1.00%, 83.92%+/-0.51%. With concentrations of MIF antibody of 50,
      100, 200, 400 microg/L, the expressions of cyclin D1 protein were 26.06%+/-0.47%,
      22.34%+/-0.75%, 18.06%+/-1.16%, 14.03%+/-0.59%, significantly lower than those of
      the control group (29.51%+/-1.28%). When HepG-2 cells were treated with different
      concentrations of MIF antibodies of 50, 100, 200, 400 microg/L the expressions of
      VEGF protein were 21.22%+/-0.68%, 19.64%+/-0.54%, 18.04%+/-0.42%, 16.59%+/-0.66%,
      significantly lower than those of the control group (23.23%+/-0.51%). With MIF
      antibody concentrations of 0, 50, 100, 200, 400 microg/L, the exudation amount of
      IL-6 were correspondingly lower [(210.67+/-9.31) pg/ml, (181.67+/-10.05) pg/ml,
      (160.50+/-6.60) pg/ml, (143.67+/-10.56) pg/ml, (118.01+/-7.48) pg/m]. CONCLUSION:
      The proliferation of HepG-2 cells was inhibited after treatment with MIF
      antibody. The inhibiting effect is caused by blocking cell cycle progression at
      G0/G1 phase, decreasing cyclin D1 protein expression, decreasing VEGF protein
      expression and decreasing the exudation amount of IL-6.

PMID- 19105938
TI  - [Frequencies of autoantibodies specific for primary biliary cirrhosis in a
      general adult population group].
AB  - OBJECTIVE: To investigate the frequencies of primary biliary cirrhosis (PBC)
      specific autoantibodies, including antimitochondrial autoantibodies (AMA) M2,
      anti-gp210 and anti-Sp100, and to assess their point prevalence rates in a
      general adult population group in Guangzhou. METHODS: Eight thousand one hundred
      twenty-six adults (mean age 43.5+/-14.6 years, range 18 to 83 years; 4248 males
      and 3878 females) were enrolled for this study. AMA and anti-nuclear antibodies
      (ANA) were screened by indirect immunofluorescence test and AMA-M2, anti-gp210
      and anti-sp100 were further detected using ELISA or immunoblotting assay. PBC
      diagnosis was made according to criteria recommended by AASLD in 2000. RESULTS:
      Of the 8126 adults tested, 35 (0.43%) and 79 (0.97%) were found to be positive
      for AMA and ANA. The positivity for both of AMA and ANA increased with aging.
      Twenty-two cases were positive for PBC-specific autoantibodies. Frequencies for
      AMA-M2, anti-sp100 and anti-gp210 in the general adult population were 0.23%,
      0.05% and 0.04% respectively and their frequency reached 0.62% in women over 40
      years. A woman among the 22 cases who was PBC-specific autoantibody positive was
      finally diagnosed as a PBC patient. CONCLUSION: Our data indicates that PBC
      specific autoantibodies exist in the general adult population at very low
      frequencies and the point prevalence rate of PBC in adults in Guangzhou is not
      less than that of other areas.

PMID- 19105939
TI  - [Monitoring vascular complications following liver transplantation using color
      Doppler flow imaging].
AB  - OBJECTIVE: To assess the value of color Doppler flow imaging (CDFI) in monitoring
      vascular complications following orthotopic liver transplantation (OLT). METHODS:
      Seven hundred ninety-two patients who received OLT from April 2002 to December
      2006 in the Organ Transplantation Center, General Hospital of Chinese People's
      Armed Police Forces, Beijing, and underwent CDFI examinations in different
      periods after OLT were enrolled in this study. Their vascular complications were
      monitored by CDFI and confirmed by angiography or spiral CT. RESULTS: Of the 792
      patients, 54 were diagnosed with vascular complications that occurred 1-360 days
      after their OLT operations. These complications occurred within 1-30 days, 31-60
      days, 61-90 days, 91-180 days, 181-360 days, with the proportions of 46.30%,
      22.22%, 14.81%, 9.26% and 7.41% respectively. The proportion of hepatic artery
      and portal vein complications and outflow occlusions were 61.11%, 35.19% and
      3.70% respectively. CONCLUSION: Most vascular complications occurred within six
      months after the OLT operation. The continuous and careful monitoring by CDFI is
      beneficial in an early diagnosis of vascular complications after OLT.

PMID- 19105940
TI  - [Construction of p-hfgl2shRNA and its effect on hfgl2 expression in vitro].
AB  - OBJECTIVE: Our previous studies have shown that an anti-sense plasmid to mouse
      fibrinogen like protein 2 (mfgl2) significantly reduced mfgl2 expression in vivo,
      markedly ameliorated inflammatory infiltration, fibrin deposition and hepatocyte
      necrosis, prolonged the survival time period and elevated the survival rate in
      Balb/cJ mice with murine hepatitis virus type 3 (MHV-3) induced fulminant
      hepatitis. This study was designed to explore the opportunity of RNA interference
      technique in the inhibitory application of hfgl2 expression, which has been
      reported to be involved in a variety of disease developments including fulminant
      viral hepatitis, acute rejection of allo/xeno transplantation and fetal loss
      syndrome. METHODS: A plasmid named p-hfgl2shRNA complimentary to the sequence
      responsible for hfgl2 was constructed; meanwhile irrelevant shRNA plasmid with a
      random combination of the p-hfgl2shRNA sequence was used as a control. A plasmid
      named pEGFP-hfgl2 expressing hfgl2-EGFP fusion protein was also constructed for
      the screening of the effect of p-hfgl2shRNA on the hfgl2 expression. By
      cotransfection of the constructed p-hfgl2shRNA and pEGFP-hfgl2 or pcDNA3.1-hfgl2
      expression plasmids into CHO cells, the inhibition of hfgl2 expression by
      hfgl2shRNA was analyzed by direct observation through fluorescent microscopy,
      FACS, real time PCR and immunohistochemistry staining. RESULTS: The experiments
      showed a significant inhibitory effect of p-hfgl2shRNA on hfgl2 expression at 48
      h post-cotransfection by observation of green fluorescent cells, FACS, real time
      PCR and immunohistochemistry staining, with the inhibitory efficiency reaching as
      high as 85.5%. CONCLUSION: The study demonstrated that p-hfgl2shRNA successfully
      interfered with hfgl2 expression in vitro. This provides a foundation to further
      explore its application in vivo.

PMID- 19105941
TI  - [Effects of farnesoid X receptor on lipid metabolism in L02 cells].
AB  - OBJECTIVE: To investigate the effects of farnesoid X receptor (FXR) on lipid
      metabolism in human hepatic L02 cells. METHODS: A steatosis model and an
      intervention model were established by treating human hepatocyte line L02 cells
      with sodium oleate or sodium oleate and sodium chenodeoxycholate (a natural
      agonist of FXR) respectively. Non-treated L02 cells served as controls. At three
      time points of 24, 48 and 72 hours, the accumulation of lipid droplets in the
      hepatocytes was observed by optical microscopy after oil red O staining, and the
      the expression of FXR and SREBP-1c receptors was detected by RT-PCR and Western
      blot. RESULTS: Compared with the controls, expressions of FXR mRNA and protein
      were down-regulated gradually in the steatosis model at 24, 48 and 72 hours, FXR
      mRNA/beta-actin mRNA was 0.186+/-0.02, 0.182+/-0.028 and 0.181+/-0.022, FXR
      protein/beta-tubulin protein was 0.105+/-0.016, 0.103+/-0.012 and 0.103+/-0.018,
      F from 0.01 to 0.14; 24 h vs 48 h, 48 vs72 h: P more than 0.05. The expressions
      of SREBP-1c mRNA and protein were increased gradually. At 24, 48 and 72 hours,
      SREBP-1c mRNA/beta-actin mRNA was 0.495+/-0.062, 0.579+/-0.064 and 0.612+/-0.067,
      SREBP-1c protein/beta-tubulin protein was 0.394+/-0.044, 0.488+/-0.066 and
      0.543+/-0.064, F from 0.80 to 4.66, 24 h vs 48 h, 48 vs 72 h: P less than 0.05.
      In the intervention model, expressions of FXR mRNA and protein were increased
      markedly compared with the steatosis model. At 24, 48 and 72 hours, FXR mRNA/beta
      actin mRNA was 0.253+/-0.041, 0.298+/-0.042 and 0.334+/-0.051, and FXR
      protein/beta-tubulin protein was 0.221+/-0.022, 0.313+/-0.041 and 0.341+/-0.046,
      F from 6.41 to 50.93, intervention models vs steatosis models at the same time
      points: P less than 0.05-0.01. Expressions of SREBP-1 c mRNA and protein were
      significantly reduced. At 24, 48 and 72 hours, SREBP-1c mRNA/beta-actin mRNA was
      0.296+/-0.038, 0.328+/-0.037 and 0.341+/-0.055, and FXR protein /beta-tubulin
      protein was 0.295+/-0.038, 0.334+/-0.047 and 0.355+/-0.054, F from 8.84 to 48.46;
      intervention models vs steatosis models at the same time point: P less than 0.01.
      Both in the steatosis model and the intervention model, content of TG and lipids
      accumulations were much more than those in the controls. Compared with the
      intervention model, levels of TG and lipids accumulation were markedly increased
      in the steatosis model at 24, 48, 72 hours. At 24, 48 and 72 hours, TG/cellular
      total protein in microg/mg was 173.0+/-20.5, 253.4+/-36.1 and 361.2+/-50.7 in the
      steatosis model, while in the intervention model the data was 84.1+/-17.2,
      113.0+/-14.5 and 127.2+/-20.1, F from 38.70 to 268.13, intervention models vs
      steatosis models at the same time point: P less than 0.01. CONCLUSION: Expression
      of FXR is closely associated with lipid homeostasis in hepatocytes. Up-regulation
      of the expression of FXR may improve lipidosis in L02 cells. Its possible
      mechanism involves reduction of SREBP-1c expression and lipogenesis in
      hepatocytes.

PMID- 19105942
TI  - [Clinical and pathological study of 30 patients with acute hydropic-type severe
      hepatitis].

PMID- 19105943
TI  - [The effects of Ginkgo biloba extract on hepatic fibrosis in diabetic rats].

PMID- 19105944
TI  - [Role of CD163/HO-1 pathway in a rat acute liver failure model].

PMID- 19105945
TI  - [The role of smac and its downstream pathway played in LPS induced apoptosis in
      L02 liver cells].

PMID- 19105946
TI  - [The effects of curcumin on the expression of acetyl-CoA carboxylase of HL-7702
      cells].

PMID- 19105947
TI  - [Expression of Pim-2 in normal liver and hepatocellular carcinoma tissues].

PMID- 19105948
TI  - [The application of HCV test strategy].

PMID- 19105949
TI  - [Interferon gamma and the treatment of hepatic fibrosis].

PMID- 19105950
TI  - [SIRT1--a potential target for the therapy of nonalcoholic steatohepatitis].

PMID- 19105951
TI  - Interaction of dengue virus envelope protein with endoplasmic reticulum-resident
      chaperones facilitates dengue virus production.
AB  - Dengue virus infection is an important mosquito-borne disease and a public health
      problem worldwide. A better understanding of interactions between human cellular
      host and dengue virus proteins will provide insight into dengue virus replication
      and cellular pathogenesis. The glycosylated envelope protein of dengue virus,
      DENV E, is processed in the endoplasmic reticulum of host cells and therefore
      reliant on host processing functions. The complement of host ER functions
      involved and nature of the interactions with DENV E has not been thoroughly
      investigated. By employing a yeast two-hybrid assay, we found that domain III of
      DENV E interacts with human immunoglobulin heavy chain binding protein (BiP). The
      relevance of this interaction was demonstrated by co-immunoprecipitation and co
      localization of BiP and DENV E in dengue virus-infected cells. Using the same
      approach, association of DENV E with two other chaperones, calnexin and
      calreticulin was also observed. Knocking-down expression of BiP, calnexin, or
      calreticulin by siRNA significantly decreased the production of infectious dengue
      virions. These results indicate that the interaction of these three chaperones
      with DENV E plays an important role in virion production, likely facilitating
      proper folding and assembly of dengue proteins.

PMID- 19105952
TI  - DDPH ameliorated oxygen and glucose deprivation-induced injury in rat hippocampal
      neurons via interrupting Ca2+ overload and glutamate release.
AB  - Our previous work has demonstrated that DDPH (1-(2, 6-dimethylphenoxy)-2-(3, 4
      dimethoxyphenylethylamino) propane hydrochloride), a competitive alpha(1)
      adrenoceptor antagonist, could improve cognitive deficits, reduce
      histopathological damage and facilitate synaptic plasticity in vivo possibly via
      increasing NR2B (NMDA receptor 2B) expression and antioxidation of DDPH itself.
      The present study further evaluated effects of DDPH on OGD (Oxygen and glucose
      deprivation)-induced neuronal damage in rat primary hippocampal cells. The
      addition of DDPH to the cultured cells 12 h before OGD for 4 h significantly
      reduced neuronal damage as determined by MTT (3-(4,5-dimethylthiazol-2-yl)-2,5
      diphenyltetrazolium bromide) assay and LDH (lactate dehydrogenase) release
      experiments. The effects of DDPH on intracellular calcium concentration were
      explored by Fura-2 based calcium imaging techniques and results showed that DDPH
      at the dosages of 5 microM and 10 microM suppressed the increase of intracellular
      calcium ([Ca(2+)](i)) stimulated by 50 mM KCl in Ca(2+)-containing extracellular
      solutions. However, DDPH couldn't suppress the increase of [Ca(2+)](i) induced by
      both 50 microM glutamate in Ca(2+)-containing extracellular solutions and 20
      microM ATP (Adenosine Triphosphate) in Ca(2+)-free solution. These results
      indicated that DDPH prevented [Ca(2+)](i) overload in hippocampal neurons by
      blocking Ca(2+) influx (voltage-dependent calcium channel) but not Ca(2+)
      mobilization from the intracellular Ca(2+) store in endoplasm reticulum (ER). We
      also demonstrated that DDPH could decrease glutamate release when hippocampal
      cells were subjected to OGD. These observations demonstrated that DDPH protected
      hippocampal neurons against OGD-induced damage by preventing the Ca(2+) influx
      and decreasing glutamate release.

PMID- 19105953
TI  - Preventive mechanisms of agmatine against ischemic acute kidney injury in rats.
AB  - The excitation of renal sympathetic nervous system plays an important role in the
      development of ischemic acute kidney injury in rats. Recently, we found that
      agmatine, an adrenaline alpha(2)/imidazoline I(1)-receptor agonist, has
      preventive effects on ischemic acute kidney injury by suppressing the enhanced
      renal sympathetic nerve activity during renal ischemia and by decreasing the
      renal venous norepinephrine overflow after reperfusion. In the present study, we
      investigated preventive mechanisms of agmatine against ischemic acute kidney
      injury in rats. Ischemic acute kidney injury was induced by clamping the left
      renal artery and vein for 45 min followed by reperfusion, 2 weeks after the
      contralateral nephrectomy. Pretreatment with efaroxan (30 mumol/kg, i.v.), an
      alpha(2)/I(1)-receptor antagonist, abolished the suppressive effects of agmatine
      on the enhanced renal sympathetic nerve activity during renal ischemia and on the
      elevated norepinephrine overflow after reperfusion, and eliminated the preventing
      effects of agmatine on the ischemia/reperfusion-induced renal dysfunction and
      histological damage. On the other hand, pretreatment with yohimbine (6 mumol/kg,
      i.v.), an alpha(2)-receptor antagonist, eliminated the preventing effects of
      agmatine on the ischemia/reperfusion-induced renal injury and norepinephrine
      overflow, without affecting the lowering effect of agmatine on renal sympathetic
      nerve activity. These results indicate that agmatine prevents the ischemic renal
      injury by sympathoinhibitory effect probably via I(1) receptors in central
      nervous system and by suppressing the norepinephrine overflow through alpha(2) or
      I(1) receptors on sympathetic nerve endings.

PMID- 19105954
TI  - Mouse models of retinal ganglion cell death and glaucoma.
AB  - Once considered too difficult to use for glaucoma studies, mice are now becoming
      a powerful tool in the research of the molecular and pathological events
      associated with this disease. Often adapting technologies first developed in
      rats, ganglion cell death in mice can be induced using acute models and chronic
      models of experimental glaucoma. Similarly, elevated IOP has been reported in
      transgenic animals carrying defects in targeted genes. Also, one group of mice,
      from the DBA/2 line of inbred animals, develops a spontaneous optic neuropathy
      with many features of human glaucoma that is associated with IOP elevation caused
      by an anterior chamber pigmentary disease. The advent of mice for glaucoma
      research is already having a significant impact on our understanding of this
      disease, principally because of the access to genetic manipulation technology and
      genetics already well established for these animals.

PMID- 19105955
TI  - Trichomonas vaginalis: the adhesins AP51 and AP65 bind heme and hemoglobin.
AB  - Trichomonas vaginalis is the cause of human trichomoniasis, the most common non
      viral sexually transmitted disease worldwide. Although acquisition of iron by
      binding to host hemoglobin through distinct receptor(s) has been described, no
      specific heme- or hemoglobin-binding site has been reported in this parasite. To
      determine the presence of hemoglobin-binding protein(s), membrane proteins were
      subjected to hemoglobin-affinity chromatography. Eluted proteins were analysed by
      SDS-PAGE. Two protein bands of 48 and 63 kDa were detected. Competition assay
      with an excess amount of hemoglobin or hemin in hemoglobin-affinity
      chromatography could block the 63- and 48-kDa bands, respectively. Further
      analysis by mass spectrometry indicated that the 48- and 63-kDa proteins had
      identity with two T. vaginalis adhesins: AP51 and AP65, respectively. This study
      confirms the existence of multifunctional proteins in T. vaginalis, and suggested
      that AP51 and AP65, besides serving as adhesion molecules, could also act as heme
      and hemoglobin-binding proteins.

PMID- 19105956
TI  - Babesia bovis: effect of Albumax II and orotic acid in a low-serum in vitro
      culture.
AB  - Bovine serum is an essential factor for the continuous in vitro growth of Babesia
      bovis parasites. Culture media typically contain 40% (v/v) of bovine serum. In
      the present study assays with low-serum media were performed. The growth of B.
      bovis Mo7 was successively lower in media with 30%, 20% and, principally, with
      10% of serum. Without serum, the parasites were not able to propagate. In media
      with 10% of serum, the supplementation with Albumax II improved visibly the
      growth of B. bovis at the end of each cycle. Regarding the addition of orotic
      acid, no considerable effect was observed in media with 20% or 10% of serum, with
      or without Albumax II. B. bovis parasites cultured in vitro in all these media
      maintain their typical morphology during the intraerythrocytic stages.

PMID- 19105957
TI  - Molecular imaging of the pancreas in small animal models.

PMID- 19105958
TI  - Electronic clinical challenges and images in GI. Image 1.

PMID- 19105961
TI  - Liver fibrosis: challenges of the new era.

PMID- 19105960
TI  - Treatment of HBV/HCV coinfection: releasing the enemy within.

PMID- 19105962
TI  - Scope early and often in ulcerative colitis and Crohn's colitis?

PMID- 19105963
TI  - Do we really need alternatives to polymorphonuclear cells counting in ascitic
      fluid?

PMID- 19105965
TI  - Clinical challenges and images in GI. Image 3: Madelung syndrome.

PMID- 19105964
TI  - Hypoxia-inducible factor-dependent repression of equilibrative nucleoside
      transporter 2 attenuates mucosal inflammation during intestinal hypoxia.
AB  - BACKGROUND & AIMS: The surface of the intestinal mucosa is particularly prone to
      hypoxia-induced inflammation. Previous studies implicated signaling via
      extracellular adenosine in endogenous attenuation of intestinal inflammation; we
      investigated whether epithelial adenosine transport could reduce hypoxia-induced
      inflammation of the mucosa. METHODS: We performed in vitro studies of epithelial
      adenosine uptake and nucleoside transport using cultured epithelial cells. In
      vivo studies of ambient hypoxia levels were performed using mice with conditional
      loss of hypoxia-inducible factor (HIF)-alpha expression in the colon. RESULTS:
      Studies of epithelial adenosine transport under hypoxic conditions showed that
      extracellular adenosine uptake occurs mainly at the apical surface of epithelial
      cells and is attenuated by hypoxia. Subsequent transcriptional studies suggested
      high expression levels of the equilibrative nucleoside transporter-2 (ENT2) in
      human epithelial cells and revealed ENT2 repression during hypoxia. Studies with
      promoter constructs, including site-directed mutagenesis, transcription factor
      binding assays, and HIF loss and gain of function showed a central role of HIF
      1alpha in transcriptional repression of ENT2 during hypoxia. Similarly,
      transcriptional repression of ENT2 by ambient hypoxia was abolished in
      conditional HIF-1alpha mutant mice in vivo. Functional studies using RNA
      interference showed that loss of epithelial ENT2 was associated with reduced
      adenosine uptake in vitro, whereas pharmacologic inhibition of ENT2 attenuated
      hypoxia-induced inflammation of the mucosa in vivo. CONCLUSIONS: HIF-1alpha
      dependent repression of ENT2 increases mucosal adenosine signaling and attenuates
      hypoxia-associated inflammation of the intestine.

PMID- 19105966
TI  - Survey of six bee viruses using RT-PCR in Northern Thailand.
AB  - Six honey bee viruses were surveyed using RT-PCR in Northern Thailand where about
      80% of Thai apiaries are located. Tested samples were found to be positive for
      deformed wing virus (DWV), acute bee paralysis virus (ABPV), sacbrood virus (SBV)
      and Kashmir bee virus (KBV). In the collected samples, neither chronic bee
      paralysis virus nor black queen cell virus nucleic acids could be detected. It
      was found that DWV was the most widespread and ABPV was the second most
      prevalent. Kashmir bee virus was found only in the Lampang province where high
      infestation of Varroa destructor mite occurred. Tropilaelaps, European foulbrood,
      and Chalkbrood diseases were found in some apiaries.

PMID- 19105967
TI  - Multifunctional effect of epigallocatechin-3-gallate (EGCG) in downregulation of
      gelatinase-A (MMP-2) in human breast cancer cell line MCF-7.
AB  - AIMS: The tumor inhibiting property of green tea polyphenol epigallocatechin-3
      gallate (EGCG) is well documented. Studies reveal that matrix-metalloproteinases
      (MMPs) play pivotal roles in tumor invasion through degradation of basement
      membranes and extracellular matrix (ECM). We studied the effect of EGCG on
      matrixmetalloproteinases-2 (MMP-2), the factors involved in activation, secretion
      and signaling molecules that might be involved in the regulation of MMP-2 in
      human breast cancer cell line, MCF-7. MAIN METHODS: MCF-7 was treated with EGCG
      (20 muM, 24 h), the effect of EGCG on MMP-2 expression, activity and its
      regulatory molecules were studied by gelatin zymography, Western blot,
      quantitative and semi-quantitative real time RT-PCR, immunoflourescence and cell
      adhesion assay. KEY FINDINGS: EGCG treatment reduced the activity, protein
      expression and mRNA expression level of MMP-2. EGCG treatment reduced the
      expression of focal adhesion kinase (FAK), membrane type-1-matrix
      metalloproteinase (MT1-MMP), nuclear factor-kappa B (NF-kB), vascular endothelial
      growth factor (VEGF) and reduced the adhesion of MCF-7 cells to ECM, fibronectin
      and vitronectin. Real time RT-PCR revealed a reduced expression of integrin
      receptors alpha5, beta1, alphav and beta3 due to EGCG treatment. SIGNIFICANCE:
      Down regulation of expression of MT1-MMP, NF-kB, VEGF and disruption of
      functional status of integrin receptors may indicate decreased MMP-2 activation;
      low levels of FAK expression might indicate disruption in FAK-induced MMP-2
      secretion and decrease in activation of phosphatidyl-inositol-3-kinase (PI-3K),
      extracellular regulated kinase (ERK) indicates probable hindrance in MMP-2
      regulation and induction. We propose EGCG as potential inhibitor of expression
      and activity of pro-MMP-2 by a process involving multiple regulatory molecules in
      MCF-7.

PMID- 19105968
TI  - Parameterizing the growth-decline boundary for uncertain population projection
      models.
AB  - We consider discrete time linear population models of the form n(t+1)=An(t) where
      A is a population projection matrix or integral projection operator, and n(t)
      represents a structured population at time t. It is well known that the
      asymptotic growth or decay rate of n(t) is determined by the leading eigenvalue
      of A. In practice, population models have substantial parameter uncertainty, and
      it might be difficult to quantify the effect of this uncertainty on the leading
      eigenvalue. For a large class of matrices and integral operators A, we give
      sufficient conditions for an eigenvalue to be the leading eigenvalue. By
      preselecting the leading eigenvalue to be equal to 1, this allows us to easily
      identify, which combination of parameters, within the confines of their
      uncertainty, lead to asymptotic growth, and which lead to asymptotic decay. We
      then apply these results to the analysis of uncertainty in both a matrix model
      and an integral model for a population of thistles. We show these results can be
      generalized to any preselected leading eigenvalue.

PMID- 19105969
TI  - Comparative morphological study of the venom glands of the centipede Cryptops
      iheringi, Otostigmus pradoi and Scolopendra viridicornis.
AB  - Centipedes are widely distributed over all the continents. As they are well
      adapted to urban areas they can often cause accidents to humans by injecting
      venom produced in the glands located inside their maxillipeds. The fine
      morphology of the centipede venom glands is practically unknown. This present
      study is the first comparative report on the histology, histochemistry and
      ultrastructure of the venom glands of the centipede species responsible for the
      majority of accidents to humans in Brazil: Scolopendra viridicornis, Cryptops
      iheringi and Otostigmus pradoi. In all species the glands are basically composed
      of columnar secretory cells radially disposed side by side, individually opening
      through pores in a central chitinous duct. Each secretory cell is covered by
      striated muscular fibres. The secretion has the form of small PAS positive
      granules and large hyaline secretory bromophenol blue positive vacuoles,
      indicating the presence of neutral polysaccharides and protein. The secretion is
      conducted through the secretory cell necks to the pores, which open into the
      central chitinous duct. The results indicate a great similarity both in
      morphology and primary chemical composition of the venom among the studied
      species, except for the size of the glands, which is proportional to the body
      dimensions of each species.

PMID- 19105970
TI  - Habitual traffic noise at home reduces cardiac parasympathetic tone during sleep.
AB  - The relationships between road and rail traffic noise with pre-ejection period
      (PEP) and with respiratory sinus arrhythmia (RSA) during sleep, as indices of
      cardiac sympathetic and parasympathetic nervous system tone, were investigated in
      the field (36 subjects, with 188 and 192 valid subject nights for PEP and RSA,
      respectively). Two analyses were conducted. The first analysis investigated the
      overall relationships across the entire sleep period. A second analysis
      investigated differences in the relationships between the first and second halves
      of the sleep period. Separate multilevel linear regression models for PEP and RSA
      were employed. Potential covariates for each model were selected from the same
      pool of variables, which included: gender, age, body-mass index, education level,
      traffic noise source type, intake of medication, caffeine, alcohol and cigarette
      smoke, and hindrance during sleep due to the ambulatory recordings. RSA models
      were adjusted for respiration rate. Mean indoor traffic noise exposure was
      negatively related to mean RSA during the sleep period, specifically during the
      second half of the sleep period. Both respiration rate and age were negatively
      associated with RSA. No significant relationships were observed for PEP. The
      results indicate that higher indoor traffic noise exposure levels may lead to
      cardiac parasympathetic withdrawal during sleep, specifically during the second
      half of the sleep period. No effect of indoor traffic noise on cardiac
      sympathetic tone was observed.

PMID- 19105971
TI  - A stearylated CPP for delivery of splice correcting oligonucleotides using a non
      covalent co-incubation strategy.
AB  - Aberrations in splicing patterns play a significant role in several diseases, and
      splice correction, together with other forms of gene regulation, is consequently
      an emerging therapeutic target. In order to achieve successful oligonucleotide
      transfection, efficient delivery vectors are generally necessary. In this study
      we present one such vector, the chemically modified cell-penetrating peptide
      (CPP) TP10, for efficient delivery of a splice-correcting 2'-OMe RNA
      oligonucleotide. Utilizing a functional splice correction assay, we assessed the
      transfection efficiency of non-covalent complexes of oligonucleotides and
      stearylated or cysteamidated CPPs. Stearylation of the CPPs Arg9 and penetratin,
      as well as cysteamidation of MPG and TP10, did not improve transfection, whereas
      the presence of an N-terminal stearyl group on TP10 improved delivery efficiency
      remarkably compared to the unmodified peptide. The splice correction levels
      observed with stearyl-TP10 are in fact in parity with the effects seen with the
      commercially available transfection agent Lipofectamine 2000. However, the
      inherent toxicity associated with cationic lipid-based transfections can be
      completely eliminated when using the stearylated TP10, making this vector highly
      promising for non-covalent delivery of negatively charged oligonucleotides.

PMID- 19105972
TI  - Non-invasive monitoring of BMP-2 retention and bone formation in composites for
      bone tissue engineering using SPECT/CT and scintillation probes.
AB  - Non-invasive imaging can provide essential information for the optimization of
      new drug delivery-based bone regeneration strategies to repair damaged or
      impaired bone tissue. This study investigates the applicability of nuclear
      medicine and radiological techniques to monitor growth factor retention profiles
      and subsequent effects on bone formation. Recombinant human bone morphogenetic
      protein-2 (BMP-2, 6.5 microg/scaffold) was incorporated into a sustained release
      vehicle consisting of poly(lactic-co-glycolic acid) microspheres embedded in a
      poly(propylene fumarate) scaffold surrounded by a gelatin hydrogel and implanted
      subcutaneously and in 5-mm segmental femoral defects in 9 rats for a period of 56
      days. To determine the pharmacokinetic profile, BMP-2 was radiolabeled with
      (125)I and the local retention of (125)I-BMP-2 was measured by single photon
      emission computed tomography (SPECT), scintillation probes and ex vivo
      scintillation analysis. Bone formation was monitored by micro-computed tomography
      (microCT). The scaffolds released BMP-2 in a sustained fashion over the 56-day
      implantation period. A good correlation between the SPECT and scintillation probe
      measurements was found and there were no significant differences between the non
      invasive and ex-vivo counting method after 8 weeks of follow up. SPECT analysis
      of the total body and thyroid counts showed a limited accumulation of (125)I
      within the body. Ectopic bone formation was induced in the scaffolds and the
      femur defects healed completely. In vivo microCT imaging detected the first signs
      of bone formation at days 14 and 28 for the orthotopic and ectopic implants,
      respectively, and provided a detailed profile of the bone formation rate.
      Overall, this study clearly demonstrates the benefit of applying non-invasive
      techniques in drug delivery-based bone regeneration strategies by providing
      detailed and reliable profiles of the growth factor retention and bone formation
      at different implantation sites in a limited number of animals.

PMID- 19105973
TI  - Multiparticulate formulation approach to pulsatile drug delivery: current
      perspectives.
AB  - In the body under physiological conditions, many vital functions are regulated by
      transient release of bioactive substances at a specific time and site. Thus, to
      mimic the function of living systems and in view of emerging chronotherapeutic
      approaches, pulsatile delivery, which is meant to release a drug following
      programmed lag phase, has attracted increasing interest in recent years. In
      pursuit of pulsatile release, various design strategies have been proposed,
      broadly categorized into single-unit and multiple-unit systems. However, in
      recent pharmaceutical applications involving pulsatile delivery, multiparticulate
      dosage forms are gaining much favor over single-unit dosage forms because of
      their potential benefits like predictable gastric emptying, no risk of dose
      dumping, flexible release patterns and increased bioavailability with less inter-
      and intra-subject variability. Based on these premises, the aim of the present
      review is to survey the main multiparticulate pulsatile delivery systems, for
      which the swelling and rupturing; dissolution or erosion; and changed
      permeability of the coating membrane are primarily involved in the control of
      release. The development of low density floating multiparticulate pulsed-release
      dosage forms possessing gastric retention capabilities has also been addressed
      with increasing focus on the upcoming multiparticulate-pulsatile technologies
      being exploited on an industrial scale.

PMID- 19105974
TI  - Variations in excitatory and inhibitory postsynaptic protein content in rat
      cerebral cortex with respect to aging and cognitive status.
AB  - Age-related cognitive impairments are associated with structural and functional
      changes in the cerebral cortex. We have previously demonstrated in the rat that
      excitatory and inhibitory pre- and postsynaptic changes occur with respect to age
      and cognitive status; however, in aged cognitively impaired animals, we have
      shown a significant imbalance in postsynaptic markers of excitatory versus
      inhibitory synapses, using markers of excitatory versus inhibitory
      neurotransmitter-related scaffolding proteins [postsynaptic density-95
      (PSD95)/synapse associated protein-90 (SAP90) and gephyrin, respectively]. The
      present study focuses on whether the expression of various excitatory and
      inhibitory postsynaptic proteins is affected by ageing and cognitive status.
      Thus, aged animals were segregated into aged cognitively impaired (AI) and aged
      cognitively unimpaired (AU) groups using the Morris water maze. We applied
      Western immunoblotting to reveal the expression patterns of a number of relevant
      excitatory and inhibitory receptors in the prefrontal and parietal cortices of
      young (Y), AU and AI animals, and performed semi-quantitative analyses to
      statistically tabulate changes among the three animal groups. A significant
      increase in the inhibitory postsynaptic scaffold protein, gephyrin, was observed
      in the parietal cortex of AI animals. Similarly, an increase in GABA(A) receptor
      subunit alpha1 was observed in the parietal cortex of AI animals. An increase in
      the excitatory N-methyl-d-aspartate receptor subunit N-methyl-d-aspartate
      receptor 1 expression was observed in the parietal cortex of AI animals, whereas
      a significant decrease in AMPA receptor subunit glutamate receptor 2 expression
      was found in the prefrontal cortex of AI animals. Finally, the excitatory,
      postsynaptic neuronal cell-adhesion receptor, neuroligin-1, was found to be
      significantly increased in both the prefrontal and parietal cortical areas of AI
      animals.

PMID- 19105975
TI  - Behavioral sensitization to cocaine is associated with increased glutamate
      receptor trafficking to the postsynaptic density after extended withdrawal
      period.
AB  - Glutamatergic signaling plays an important role in the behavioral and molecular
      plasticity observed in behavioral sensitization to cocaine. Redistribution of the
      glutamate receptors in the synaptosomal membrane fraction was investigated in the
      nucleus accumbens, dorsolateral striatum, and ventral tegmental area at 1 or 21
      days of withdrawal in behaviorally sensitized rats. At 1 day of withdrawal, there
      were no changes in either tissue level or redistribution of glutamate receptors
      in nucleus accumbens core and shell and ventral tegmental area. At 21 days of
      withdrawal, there was a decrease in the expression of mGluR2/3 protein in core
      and shell, an increase in GluR1 and a decrease in Homer1b/c proteins in the
      nucleus accumbens core tissue. In dorsolateral striatum, the tissue level of
      NMDAR2B protein was increased. Moreover, there was an augmented presence of AMPA
      (GluR1, GluR2), NMDA (NMDAR1, 2A, 2B), and group 1 metabotropic glutamate
      receptor (mGluR5) proteins in the synaptosomal fraction in core and shell of the
      nucleus accumbens. There was also an increase in synaptosomal mGluR2/3 protein in
      nucleus accumbens core. The redistribution of glutamate receptors was selective
      for nucleus accumbens since no changes were observed in the dorsolateral striatum
      and ventral tegmental area. While the tissue level of the Homer1b/c protein was
      selectively reduced in nucleus accumbens core, that of PSD95, PICK1, and actin
      was not changed in any of the brain regions examined. However, the synaptosomal
      membrane fraction level of Homer1b/c and PSD95 was increased in nucleus accumbens
      core and shell, with no changes in PICK1, and a decrease in actin protein. These
      observations suggest that significant redistribution of glutamate receptors and
      postsynaptic scaffolding proteins into synaptosomal membrane fraction is
      associated with withdrawal from behavioral sensitization to cocaine.

PMID- 19105976
TI  - Age-related reduction in microcolumnar structure correlates with cognitive
      decline in ventral but not dorsal area 46 of the rhesus monkey.
AB  - The age-related decline in cognitive function that is observed in normal aging
      monkeys and humans occurs without significant loss of cortical neurons. This
      suggests that cognitive impairment results from subtle, sub-lethal changes in the
      cortex. Recently, changes in the structural coherence in mini- or microcolumns
      without loss of neurons have been linked to loss of function. Here we use a
      density map method to quantify microcolumnar structure in both banks of the
      sulcus principalis (prefrontal cortical area 46) of 16 (ventral) and 19 (dorsal)
      behaviorally tested female rhesus monkeys from 6 to 33 years of age. While total
      neuronal density does not change with age in either of these banks, there is a
      significant age-related reduction in the strength of microcolumns in both regions
      on the order of 40%. This likely reflects a subtle but definite loss of
      organization in the structure of the cortical microcolumn. The reduction in
      strength in ventral area 46 correlates with cognitive impairments in learning and
      memory while the reduction in dorsal area 46 does not. This result is congruent
      with published data attributing cognitive functions to ventral area 46 that are
      similar to our particular cognitive battery which does not optimally tap
      cognitive functions attributed to dorsal area 46. While the exact mechanisms
      underlying this loss of microcolumnar organization remain to be determined, it is
      plausible that they reflect age-related alterations in dendritic and/or axonal
      organization which alter connectivity and may contribute to age-related declines
      in cognitive performance.

PMID- 19105977
TI  - Thyroid inhibitory, antiperoxidative and hypoglycemic effects of stigmasterol
      isolated from Butea monosperma.
AB  - Stigmasterol, isolated from the bark of Butea monosperma was evaluated for its
      thyroid hormone and glucose regulatory efficacy in mice. Its administration at
      2.6 mg/kg/d for 20 days reduced serum triiodothyronine (T(3)), thyroxin (T(4))
      and glucose concentrations as well as the activity of hepatic glucose-6
      phophatase (G-6-Pase) with a concomitant increase in insulin indicating its
      thyroid inhibiting and hypoglycemic properties. A decrease in the hepatic lipid
      peroxidation (LPO) and an increase in the activities of catalase (CAT),
      superoxide dismutase (SOD) and glutathione (GSH) suggested its antioxidative
      potential. The highest concentration tested (5.2 mg/kg) evoked pro-oxidative
      activity.

PMID- 19105978
TI  - Adenoviral vectors for improved gene delivery to the inner ear.
AB  - An important requirement for gene therapy in the inner ear is to achieve
      efficient gene delivery without damaging residual inner ear function. This can be
      achieved by delivering a high concentration of vector in a minimal volume.
      Adenovectors are well suited to meet these requirements since high quality
      concentrated vector with a high capacity for a gene payload can be produced. To
      reduce the number of vector particles and volume of delivery to the inner ear, we
      tested vectors with enhancements in cell binding and cell entry properties. We
      compared delivery of a marker gene to the inner ear using two different advanced
      generation serotype 5 adenovector designs. The first adenovector tested, AdRGD,
      has a restricted tropism of entry into cells. AdRGD is an Ad5 capsid vector with
      an arg-gly-asp (RGD) motif built into the adenovector fiber that has also been
      modified to abolish the fiber-CAR and penton-integrin interactions that provide
      the normal well characterized two-step entry pathway for adenovirus. The AdRGD
      vector has enhanced binding to alphanu integrins. The second vector, AdF2K,
      contains 7 lysine residues within the fiber knob and has been shown to have
      expanded tropism for cells in vitro and in vivo. AdF2K maintains its normal CAR
      and integrin receptors interactions and has an additional mechanism of entry via
      its ability to interact with heparan sulfate. Both vectors demonstrated effective
      delivery to the inner ear and more uniform labeling of the inner ear sensory
      epithelia than native capsid vector, when tested in vivo. Analysis of expression
      efficiency using quantitative PCR was tested in vitro on cultured macular organs
      and demonstrated that vector delivery with the AdF2K vector design yielded
      optimal delivery. The present study demonstrates that retargeting strategies can
      improve delivery to the inner ear.

PMID- 19105979
TI  - Tolliod-like gene in Crassostrea ariakensis: Molecular cloning, structural
      characterization and expression by RLO stimulation.
AB  - The BMP1/TLD-like proteinases are pleiotropic, astacin-like metalloproteinases.
      They play central roles in regulating the formation of the extracellular matrix
      (ECM) and signaling through various TGFbeta-like proteins in morphogenetic and
      homeostatic events. Here we describe the cloning, structural characterization and
      expression of Tolloid-like gene in the oyster, Crassostrea ariakensis (CaTLL).
      The full-length cDNA of CaTLL spans 3492 nucleotides including an open reading
      frame of 2811 nucleotides which encodes a hypothetical protein of 936 amino
      acids, with a molecular mass of approximately 103 kDa. The CaTLL molecule
      possessed structural features of several motifs including an N-terminal signal
      peptide sequence, a prodomain with an RTRR motif, an astacin-like domain that
      contains a conserved zinc-binding motif HELGHVIGFWHEH, five CUBs and two EGF
      domains with the arrangement CUB-CUB-EGF-CUB-EGF-CUB-CUB. The proteolytic domain
      of Ca-Tolloid shares more than 30% identity with other astacins of various
      animals from squail to mammals, indicating its conserved catalytic ability. RT
      PCR and quantitative real-time PCR analyses revealed that CaTLL showed the lowest
      expression level in hemocytes of normal groups, but was affected significantly by
      the challenge of an obligate intracellular Gram-negative bacterium, Rickettsia
      like organisms, suggesting that Ca-Tolloid might be involved in the molluscan
      immune response, and its function is more diverse than previously assumed.

PMID- 19105980
TI  - In vitro and in vivo sensitization of SW620 metastatic colon cancer cells to CDDP
      induced apoptosis by the nitric oxide donor DETANONOate: Involvement of AIF.
AB  - Tumor cells develop mechanisms that dysregulate apoptotic pathways resulting in
      resistance to cytotoxic stimuli. Primary SW480 and metastatic SW620 colon cancer
      cells are resistant to CDDP-induced apoptosis. Apoptosis-inducing factor (AIF)
      was significantly downregulated in SW620 compared to SW480 cells; while apoptotic
      mediators such as Bax, Bcl-2, and Bcl(XL) were not altered in these cell lines.
      Examination of tumor tissues from patients with colon cancer demonstrated a
      significant downregulation of AIF in patients with advanced disease. The role of
      AIF expression in resistance was examined. Several lines of evidence suggest the
      involvement of AIF expression level in the sensitivity of SW620 to CDDP-induced
      apoptosis: (1) sensitization of SW620 by the NO donor DETANONOate to CDDP-induced
      apoptosis correlated with the induction of AIF as assessed by RT-PCR and Western
      blot analysis, (2) treatment of SW620 cells with siRNA AIF, but not with control
      siRNAs, inhibited DETANONOate-induced sensitization to CDDP apoptosis, (3)
      sensitization by DETANONOate observed in vitro was corroborated in vivo in nude
      mice bearing SW620 tumor xenografts and treated with the combination of
      DETANONOate and CDDP, and (4) tumor tissues derived from the SW620 xenografts
      revealed significant upregulation of AIF and increased apoptosis by DETANONOate
      and CDDP combination treatment. Altogether, these findings underscore the
      potential therapeutic application of NO donors and subtoxic chemotherapeutic
      drugs in the treatment of advanced colon cancer resistant to conventional
      chemotherapeutic agents.

PMID- 19105981
TI  - Inhibition of human cervical carcinoma growth by cytokine-induced killer cells in
      nude mouse xenograft model.
AB  - Cervical cancer is a major cause of cancer mortality in women worldwide and is an
      important public health problem for adult women in developing countries. Despite
      aggressive treatment with surgery and chemoradiation, the outcomes for cervical
      cancer patients remain poor. In this study, the antitumor activity of cytokine
      induced killer (CIK) cells against human cervical cancer was evaluated in vitro
      and in vivo. Human peripheral blood mononuclear cells were cultured with IL-2
      containing medium in anti-CD3 antibody-coated flasks for 5 days, followed by
      incubation in IL-2-containing medium for 9 days. The resulting populations of CIK
      cells comprised 95% CD3(+), 3% CD3(-)CD56(+), 35% CD3(+)CD56(+), 11% CD4(+), <1%
      CD4(+)CD56(+), 80% CD8(+), and 25% CD8(+)CD56(+). At an effector-target cell
      ratio of 100:1, CIK cells destroyed 56% of KB-3-1 human cervical cancer cells, as
      measured by the (51)Cr-release assay. In addition, CIK cells at doses of 3 and 10
      million cells per mouse inhibited 34% and 57% of KB-3-1 tumor growth in nude
      mouse xenograft assays, respectively. This study suggests that CIK cells may be
      used as an adoptive immunotherapy for cervical cancer patients.

PMID- 19105982
TI  - Toll-like receptors-related genes in kidney transplant patients with chronic
      allograft nephropathy and acute rejection.
AB  - INTRODUCTION: Toll-like receptors (TLR) comprehend an emerging family of
      receptors that recognize pathogen-associated molecular patterns and promote the
      activation of leukocytes. Surgical trauma and ischemia-reperfusion injury are
      likely to provide exposure to endogenous ligands for TLR in virtually all kidney
      transplant recipients. METHODS: Macroarray (GEArray OHS-018.2 Series-Superarray)
      analyses of 128 genes involved in TLR signaling pathway were performed in
      nephrectomy samples of patients with chronic allograft nephropathy (CAN) and
      acute rejection (AR, vascular and non vascular). The analysis of each membrane
      was performed by GEArray Expression Analysis Suite 2.0. RESULTS: Macroarray
      profile identified a gene expression signature that could discriminate CAN and
      AR. Three genes were significantly expressed between CAN and vascular AR: Pellino
      2; IL 8 and UBE2V1. In relation to vascular and non-vascular AR, there were only
      two genes with statistical significance: IL-6 and IRAK-3. CONCLUSION: Vascular
      and non-vascular AR and CAN showed different expression of a few genes in TLR
      pathway. The analysis of nephrectomy showed that activation of TLR pathway is
      present in AR and CAN.

PMID- 19105983
TI  - Quantification of mitochondrial DNA (mtDNA) damage and error rates by real-time
      QPCR.
AB  - Mitochondrial dysfunction has reported in several diseases including diabetes,
      cancer, skeletal muscle disorders and neurodegenerative diseases such as Wolfram
      syndrome. Several different methods have evolved to study mtDNA damage including
      Southern blotting, 8-oxoG damage, or a comprehensive scanning of the
      mitochondrial genome by RFLP or TTGE analyses. However these approaches require
      large amounts of DNA or are labor intensive. The use of polymerase amplification
      of long DNA products (LRPCR) has been described by several groups and more
      recently summarized by Van Houten's group. The underlying basis use of DNA
      polymerases capable of generating long DNA products and the rationale is that any
      lesion (strand breaks, base modifications, apurinic sites) will stop a
      thermostable DNA polymerase. In this method, band density of the PCR product is
      quantified either by Southern blotting or binding of a fluorescent dye. Although
      the latter approach still has some limited use in the study gene expression, it
      is semi-quantitative and realtime PCR analysis has largely supplanted it. Direct
      application of real-time PCR to LRPCR has been made difficult because of low
      processivity and polymerization rates of the DNA polymerases used and SYBR green
      inhibition of DNA amplification. We have modified the LRPCR protocol to use the
      commercially available PfuUltra() II Fusion HS DNA Polymerase for real-time
      determination of mitochondrial DNA amplification as a means to simplify and
      improve of the accuracy for quantification of mtDNA damage.

PMID- 19105985
TI  - A maxillary laser-welded component removable partial denture: a clinical report.
AB  - Component removable partial dentures (RPDs) are fabricated in pieces and
      assembled on the definitive cast. The treatment modality described is believed by
      the authors to optimize the passive fit and frictional retention of the RPD.
      Increased frictional retention and stability is believed to improve the clinical
      performance of the RPD. Patients may thereby benefit from more esthetic and more
      durable prostheses.

PMID- 19105986
TI  - The ability of dental students and faculty to estimate the total occlusal
      convergence of prepared teeth.
AB  - STATEMENT OF PROBLEM: Total occlusal convergence (TOC) is an important aspect of
      tooth preparation, but the accuracy of its visual estimation has not been
      determined. PURPOSE: The purpose of this study was to determine which TOC angles
      are considered ideal, maximal, and minimal, and also to determine the accuracy of
      visually estimating TOC. MATERIAL AND METHODS: Thirteen dentoform teeth were
      prepared, for complete gold crown restorations, with TOC angles ranging between 
      3 and 30. Thirty students and 30 faculty members visually identified the teeth
      they believed had ideal, maximal, and minimal convergence and then estimated the
      angle of TOC for each tooth. Data were analyzed with a 2-sample binomial test and
      the 2-sample t test (alpha=.05), as well as the general linear model (the mixed
      procedure). RESULTS: Teeth selected had TOC angles of 9-12 degrees, 21-30
      degrees, and 3-12 degrees for ideal, maximal acceptability, and minimal
      acceptability, respectively. Students and faculty exhibited similar visual
      estimation capabilities. Greater accuracy of visual estimation of TOC angles
      occurred with teeth judged to have minimal or ideal convergence, as opposed to
      those with maximally acceptable angles, indicating estimation accuracy decreased
      as convergence increased. More than half of the estimates were within 5 degrees
      of the measured TOC. However, 11 ideal, 14 maximal, and 5 minimal estimates were
      judged inaccurately by 11 to 20 degrees, and 5 estimates were inaccurate by more
      than 20 degrees. There were more underestimates than overestimates. CONCLUSIONS:
      Most visual estimates were accurate, but several were inaccurate by more than 10
      degrees. The most common inaccuracies were underestimated TOC. Students and
      faculty were not significantly different in their ability to accurately estimate
      TOC. Students and faculty were less accurate when estimating large, as opposed to
      small, TOC angles.

PMID- 19105984
TI  - CXCL10 and autoimmune diseases.
AB  - CXCL10 is a 10 kDa protein, which is categorized functionally as a Th1-chemokine.
      It binds to the receptor CXCR3 and regulates immune responses through the
      activation and recruitment of leukocytes, such as, T cells, eosinophils, and
      monocytes. Recent reports have shown that serum and/or tissue expressions of
      CXCL10 are increased in various autoimmune diseases like rheumatoid arthritis
      (RA), systemic lupus rythematosus (SLE), Sjogren syndrome (SS), systemic
      sclerosis (SSc), and idiopathic inflammatory myopathy (IIM). Moreover, CXCL10 and
      CXCR3 may have important roles in leukocyte homing to inflamed tissues and in the
      perpetuation of inflammation, and therefore, tissue damage. Our recent study
      shows that CXCL10 also has a pathogenic role in bone destruction via receptor
      activator of NF-kappaB ligand (RANKL) induction in inflamed synovial tissue of
      RA. In addition to its chemotactic effect, CXCL10 may have pleiotropic functions.
      Further research on the function of this chemokine and interactions between
      CXCL10 and other cytokines and chemokines may provide therapeutic targets in
      various autoimmune diseases.

PMID- 19105987
TI  - Color stability of dental ceramics submitted to artificial accelerated aging
      after repeated firings.
AB  - STATEMENT OF PROBLEM: Color stability is an important factor to ensure the long
      term clinical success of ceramic restorations. There is a lack of information on
      how color is affected by fabrication procedures, such as the number of firings.
      PURPOSE: The purpose of this study was to evaluate the effects that the number of
      firings and type of substrate have on the color stability of dental ceramic
      submitted to artificial accelerated aging. MATERIAL AND METHODS: Sixty specimens
      were fabricated: 30 metal ceramic (Verabond II + IPS d.SIGN) and 30 all-ceramic
      (IPS d.SIGN). Specimens were divided into 3 groups (n=10), and submitted to 2, 3,
      or 4 firings (+/-900 degrees C), respectively, according to the manufacturer's
      instructions. Color readings were obtained with a spectrophotometer before and
      after artificial accelerated aging, and L*, a*, and b* coordinates and total
      color variation (Delta E) were analyzed (2-way ANOVA, Bonferroni, alpha=05).
      RESULTS: For metal ceramic specimens, differences for the L* coordinates were
      significant (P<.05) only for the group submitted to 3 firings. With respect to
      the all-ceramic specimens, smaller L* coordinates were obtained for greater a*
      and b* coordinates, indicating that the greater the number of firings, the darker
      and more reddish/yellowish the specimen. All Delta E values, for all groups, were
      below 1.0. All-ceramic specimens submitted to 3 and 4 firings presented Delta E
      means differing statistically (P<.05) from those of the metal ceramic group.
      CONCLUSIONS: The type of substrate and number of firings affected the color
      stability of the ceramic material tested. Artificial accelerated aging did not
      produce perceptible color stability changes (Delta E<1.0).

PMID- 19105988
TI  - Comparison of porcelain surface and flexural strength obtained by microwave and
      conventional oven glazing.
AB  - STATEMENT OF PROBLEM: Although the superior qualities of microwave technology are
      common knowledge in the industry, effects of microwave glazing of dental ceramics
      have not been investigated. PURPOSE: The purpose of this study was to investigate
      the surface roughness and flexural strength achieved by glazing porcelain
      specimens in a conventional and microwave oven. MATERIAL AND METHODS: Thirty
      specimens of each type of porcelain (Omega 900 and IPS d.Sign) were fabricated
      and sintered in a conventional oven. The specimens were further divided into 3
      groups (n=10): hand polished (using diamond rotary ceramic polishers), microwave
      glazed, and conventional oven glazed. Each specimen was evaluated for surface
      roughness using a profilometer. The flexural strength of each specimen was
      measured using a universal testing machine. A 2-way ANOVA and Tukey HSD post hoc
      analysis were used to determine significant intergroup differences in surface
      roughness (alpha=.05). Flexural strength results were also analyzed using 2-way
      ANOVA, and the Weibull modulus was determined for each of the 6 groups. The
      surfaces of the specimens were subjectively evaluated for cracks and porosities
      using a scanning electron microscope (SEM). RESULTS: A significant difference in
      surface roughness was found among the surface treatments (P=.02). Follow-up tests
      showed a significant difference in surface roughness between oven-glazed and
      microwave-glazed treatments (P=.02). There was a significant difference in
      flexural strength between the 2 porcelains (P<.005), but no significant
      difference in flexural strength by surface treatment (P=.48). The Weibull modulus
      value for the Omega 900 microwave-glazed group was the highest (1.9) as compared
      to the other groups. CONCLUSIONS: The surface character of microwave-glazed
      porcelain was superior to oven-glazed porcelain. Omega 900 had an overall higher
      flexural strength than IPS d.Sign. Weibull distributions of flexural strengths
      for Omega 900 oven-glazed and microwave-glazed specimens were similar. SEM
      analysis demonstrated a greater number of surface voids and imperfections in IPS
      d. Sign as compared to Omega 900.

PMID- 19105989
TI  - An in vitro evaluation of the long-term resin bond to a new densely sintered high
      purity zirconium-oxide ceramic surface.
AB  - STATEMENT OF PROBLEM: Successful long-term bonding to zirconia ceramic remains a
      challenge, requiring special cements and surface roughening by airborne-particle
      abrasion, which might negatively affect the ceramic. PURPOSE: The purpose of this
      study was to evaluate the shear bond strength (SBS) of composite resin cylinders
      to a modified zirconia surface using different luting techniques after thermal
      cycling. MATERIAL AND METHODS: Composite resin (TPH3) cylinders with a diameter
      of 3 mm were bonded to zirconia ceramics (Procera Zirconia) with a modified
      surface (RZ) and a machined surface (MZ). Three different adhesive luting cements
      (Panavia F2.0, RelyX ARC, RelyX Unicem) in combination with and without airborne
      particle abrasion (50-microm and 110-microm Al(2)O(3)) were used. RZ was bonded
      using all 3 cements with (50 mum) and without airborne-particle abrasion; with
      110 microm, only Panavia F2.0 was used. MZ was bonded using only Panavia F2.0
      with (50 microm, 110 microm) and without airborne-particle abrasion. SBS was
      tested in a universal testing machine (Instron) before and after 90 days of water
      storage and 20,000 thermal cycles (dwell time, 15 seconds). Statistical analysis
      was performed using a multifactorial ANOVA model with alpha=.05. RESULTS: Mean
      SBS ranged from 10.1 to 20.0 MPa after 3 days and from 0.16 to 14.8 MPa after
      thermal cycling. Thermal cycling decreased SBS significantly. Airborne-particle
      abrasion significantly decreased SBS to the modified surface, regardless of
      cements used. SBS to the modified zirconia surface was significantly higher than
      to the machined surface. CONCLUSIONS: SBS to the modified zirconia surface is
      higher than to airborne-particle-abraded, machined zirconia. Airborne-particle
      abrasion of the modified zirconia surface is not recommended.

PMID- 19105990
TI  - Repeatability and interdevice reliability of two portable color selection devices
      in matching and measuring tooth color.
AB  - STATEMENT OF PROBLEM: There is a need to know how shade selection devices perform
      in matching and measuring tooth color, since these functions are usually
      evaluated independently and may present significant discrepancies. PURPOSE: The
      purpose of this study was to evaluate 2 devices which offer both functions to
      test the null hypothesis that they present no differences in their repeatability
      and interdevice reliability relating to the 2 functions. MATERIAL AND METHODS:
      Thirty-one extracted anterior human teeth were measured twice, with each of the
      devices (ShadeEye NCC and VITA EasyShade), by one investigator experienced and
      calibrated with both devices. L*a*b* values and shade matches to VITA Classical
      and Vitapan 3D-Master shade guide systems were determined for all teeth. Paired t
      tests and intraclass correlation coefficients (ICCs) were used to statistically
      analyze the data (alpha=.05). RESULTS: The results showed that L*a*b* values with
      VITA EasyShade were significantly higher than those with ShadeEye NCC (P<.01),
      with a mean difference of 10.01 Delta E units. Device repeatability ICCs for
      measuring tooth color ranged from 0.693 to 0.929, with significant differences
      between devices only with respect to parameter L* (P=.042). Intradevice ICCs for
      matching tooth color ranged from 0.714 to 0.894, with significant differences
      between devices only with respect to the VITA Classical shade system (P=.042).
      Interdevice ICCs for measuring tooth color ranged from 0.402 to 0.486, with no
      significant differences between L*a*b* parameters, while interdevice matching
      reliability ranged from 0.189 to 0.430, with no significant differences between
      shade systems (P>.05). CONCLUSIONS: All tooth color parameters were higher with
      the VITA EasyShade device. Measuring repeatability of the VITA EasyShade was
      higher than the ShadeEye NCC only for the L* parameter. Matching repeatability of
      the ShadeEye NCC was higher than the VITA EasyShade for the VITA Classical
      system. Interdevice measuring reliabilities were not different for the color
      parameters, but matching reliability of the VITA Classical system was higher than
      that of the Vitapan 3D-Master.

PMID- 19105991
TI  - Coverage error of gingival shade guide systems in measuring color of attached
      anterior gingiva.
AB  - STATEMENT OF PROBLEM: It remains unclear which gingival shade guide is most
      effective in producing the best visual shade match. PURPOSE: The purpose of this
      study was to determine and compare the coverage errors (CEs) of 2 different
      gingival shade guides and their combination in a selected population. MATERIAL
      AND METHODS: The CEs of the following gingival shade guides were evaluated: (1)
      Lucitone 199, (2) IPS Gingiva, and (3) a combination of the 2 shade guide
      systems. The spectral reflectance values of the center of each gingival shade tab
      (1.5 mm in diameter) were measured (without a backing) with a spectroradiometer
      and an external light source at wavelengths from 380 nm to 780 nm at 2-nm
      intervals. All spectral reflectance measurements were made using 0-degree
      observer and 45-degree illumination and then converted to CIE values. The
      attached gingiva of 120 subjects was measured with the same protocol. The CEs of
      each of the 120 subjects' attached gingiva for each of the 2 shade guide systems
      and their combination were determined and averaged. The mean minimum CEs were
      analyzed with repeated measures ANOVA and the post hoc Tukey HSD for multiple
      comparison (alpha=.05). RESULTS: A significant difference (P<.001) was found
      among the mean minimum CEs of the 2 gingival shade guide systems and their
      combination. The Tukey HSD test revealed that the mean minimum CEs for Lucitone
      199 (Delta E 10.8 +/-4.4) were significantly different from the IPS Gingiva
      (Delta E 8.6 +/-3.6) shade guide system. However, the combination of the 2
      gingival shade guide systems (Delta E 7.9 +/-3.4) was not significantly different
      from the IPS Gingiva system, but a significant difference was found among races
      (P=.016). No interactions were found between the other tested groups. The mean CE
      for white individuals (Delta E 8.3 +/-2.5) is significantly different and less
      than the mean CE for African Americans (Delta E 10.0 +/-4.4). The CEs for Asians
      (Delta E=9.1 +/-4.3) and others (Delta E 9.0 +/-4.4) are not significantly
      different from CEs for whites or African Americans. CONCLUSIONS: The IPS Gingiva
      shade guide system resulted in the lowest CEs compared to the Lucitone 199 shade
      guide system. The mean CE for Lucitone 199 was significantly greater than the
      mean CE for IPS Gingiva and for the combination of the 2 guides. The mean CE for
      whites is significantly different and less than the mean CE for African
      Americans. The CEs for Asians and others are not significantly different from CEs
      for whites or African Americans.

PMID- 19105992
TI  - Effect of severely reduced bone support on the stress field developed within the
      connectors of three types of cross-arch fixed partial dentures.
AB  - STATEMENT OF PROBLEM: Increased technical failure has been reported for cross
      arch fixed partial dentures (FPDs), particularly for cantilever units with
      minimum osseous support. PURPOSE: The purpose of this study was to investigate
      the effect of severely reduced bone support on the stress field developed within
      the connectors for 3 types of cross-arch FPDs. MATERIAL AND METHODS: Six digital
      parametric models were developed, derived from a 3-dimensional (3-D) initial
      model. The latter simulated a human mandible, dentate bilaterally to second
      premolars, with normal height of alveolar bone. In the initial model, the teeth
      were prepared and splinted with a cross-arch FPD bilaterally with one of the
      following: no cantilever, 1-unit cantilever, or 2-unit cantilever. All structures
      were obtained from computed tomography (CT)-scan images or constructed in 3-D
      computer-aided design (CAD) and reverse engineering environments. A 3-D finite
      element analysis (3-D FEA) was performed. RESULTS: The reduction of the alveolar
      bone in the no-cantilever FPD model caused a greater increase of stress in the
      region of connectors among the splinted teeth in comparison to the 1- and 2-unit
      cantilever FPD model. The stress state within the connectors of the cantilever
      segment remained constant. The connectors proximal to the retaining abutment
      demonstrated the highest stress values, independent of the osseous support. The
      stress values in the region of the same connectors in the 2-unit cantilever
      restoration were almost double, compared to the 1-unit cantilever model.
      Decreasing the osseous level in the 1- and 2-unit cantilever FPD models caused
      milder stress distribution and magnitude in the region of connectors among the
      splinted teeth. CONCLUSIONS: The stress field developed within the connectors of
      the cantilever segment is independent of the osseous level. The stress field
      within the connectors among splinted teeth depends on the osseous support and
      both the presence and length of the cantilever segment. Furthermore, this study
      indicates that adding a cantilever segment has a positive effect on the stress
      behavior of the splinted teeth connectors in situations of reduced osseous
      support.

PMID- 19105993
TI  - Effect of burn-out temperature on magnetic keepers in cast noble metal alloy
      posts.
AB  - STATEMENT OF PROBLEM: Early loss of magnetic keepers in cast gold posts is seen
      in clinical practice. PURPOSE: The purpose of this vitro study was to investigate
      the effect of burn-out temperature on the retention of magnetic keepers in cast
      gold alloy and on the thickness of the oxide layer at the keeper-alloy interface.
      MATERIAL AND METHODS: One hundred and five keepers (Magfit EX) were cast with
      gold alloy (Protor 3) at 3 different burn-out temperatures: 500 degrees C, 600
      degrees C, or 700 degrees C (n=35). To test for retention of keepers, 60
      specimens (n=20) were tested to failure in tension mode in a universal testing
      machine (UTM); 45 specimens (n=15) were sectioned, and the interface was
      evaluated under a scanning electron microscope (SEM). Tensile force data were
      analyzed with 1-way ANOVA, and SEM data were analyzed with 1-way repeated
      measures ANOVA. Bonferroni multiple comparisons were performed for post hoc
      analysis (alpha=.05). RESULTS: Retention of the keepers was significantly higher
      at lower burn-out temperatures (P<.001). The retention of the keepers became
      unpredictable and immediate failures were observed at a burn-out temperature of
      700 degrees C. Oxide formation at the keeper-alloy interface was significantly
      less at lower burn-out temperatures (P<.001). CONCLUSIONS: A burn-out temperature
      of 500 degrees C for casting the Magfit EX keeper with type IV high-strength gold
      alloy is recommended.

PMID- 19105994
TI  - A simple method to transfer the selected path of insertion of a removable partial
      denture intraorally.

PMID- 19105995
TI  - Support for small molecule inhibition of aquaporin 4.

PMID- 19105996
TI  - Lead dustfall from demolition of scattered site family housing: developing a
      sampling methodology.
AB  - BACKGROUND: Over 3000 older homes containing lead-based paint are demolished in
      Chicago each year. While previous studies investigating large multifamily housing
      demolitions have shown high levels of lead in dustfall, dispersed single-family
      housing demolition have yet to be assessed. Presently, no standards exist to
      regulate the extent of lead dustfall from housing demolition. OBJECTIVES: We
      studied ten residences in Chicago undergoing demolition and debris removal and
      compared dustfall rates to five standing homes from March to October 2006.
      METHODS: Dustfall was measured using a modification of APHA Method 502; samplers
      consisted of plastic buckets filled with 1l of deionized water, elevated to
      breathing zone height and placed around the demolition site perimeter. Laboratory
      analysis consisted of filtration, acid digestion and analysis by ICP/MS. RESULTS:
      During demolition, the geometric mean lead dustfall (n=43 at 10 locations) was
      64.1 microgPb/m(2)/h (range: 1.3-3902.5), while the geometric mean lead dustfall
      for areas with no demolition (n=18 at 6 locations) was 12.9 microgPb/m(2)/h
      (range: 1.8-54.5). This difference was highly statistically significant
      (p=0.0004). When dust suppression measures were used, dustfall lead levels were
      lower, although the difference was not statistically significant. The geometric
      mean lead dustfall with dust suppression (n=25 at five locations) and without
      (n=22 at six locations) was 48 Pbmicrog/m(2)/h and 74.6 microgPb/m(2)/h,
      respectively. CONCLUSION: Demolition dustfall lead levels are much higher than
      background levels of lead during demolition of single-family housing and may
      constitute a yet uncharacterized but important source of lead exposure to nearby
      residents. Simple dust suppression methods are likely to reduce the contamination
      considerably.

PMID- 19105997
TI  - Bilateral asymmetry in permanent dentition of 13 pre-conquest samples from
      Argentina (South America).
AB  - Bilateral asymmetry is an important field of study in anthropology. The
      evaluation of bilateral asymmetry of 44 dental non-metric traits of permanent
      dentition is carried out in this study on 376 adult skulls from different
      archaeological sites in Argentina (South America). From a total of 44 traits
      studied, just 12 (27% of the total traits expressed) presented Bilateral Index
      (BI) values lower than 100% (between 92% and 99%). Results suggest that the
      expression of all dental traits is probably bilateral. These results show the
      importance of analysis of bilateral asymmetry for assignment of taxonomic and
      population value of non-metric dental traits.

PMID- 19105998
TI  - Relationship between first polar body morphology before intracytoplasmic sperm
      injection and fertilization rate, cleavage rate, and embryo quality.
AB  - OBJECTIVES: To evaluate the influence of the morphology of the first polar body
      (PB) on intracytoplasmic sperm injection (ICSI) outcomes. METHODS: The morphology
      of the first PB was assessed in 3177 metaphase II oocytes and classified as:
      intact and normal size, fragmented, or enlarged size. The rates of fertilization,
      cleavage, and embryo quality were evaluated on day 2. RESULTS: The rates of
      fertilization, cleavage, and formation of good quality embryos resulting from the
      insemination of oocytes with an enlarged first PB (20.7%, 18.7%, and 5.0%,
      respectively) were significantly lower than those for oocytes with an intact
      first PB of normal size (70.8%, 62.5%, and 19%, respectively) or a fragmented
      first PB (69.7%, 60.5%, and 17.1%, respectively). Rates did not differ
      significantly between oocytes with an intact first PB of normal size and oocytes
      with a fragmented first PB (P>0.05). CONCLUSIONS: The presence of an enlarged PB
      is related to poorer rates of fertilization, cleavage, and top quality embryos.
      However, identification of first PB fragmentation does not seem to interfere with
      ICSI outcomes.

PMID- 19105999
TI  - Permeability evaluation of 45S5 Bioglass-based scaffolds for bone tissue
      engineering.
AB  - Permeability is a key parameter for microstructural design of scaffolds, since it
      is related to their capability for waste removal and nutrients/oxygen supply. In
      this framework, Darcy's experiments were carried out in order to determine the
      relationship between the pressure drop gradient and the fluid flow velocity in
      Bioglass-based scaffolds to obtain the scaffold's permeability. Using deionised
      water as working fluid, the measured average permeability value on scaffolds of
      90-95% porosity was 1.96 x 10(-9) m(2). This value lies in the published range of
      permeability values for trabecular bone.

PMID- 19106000
TI  - Measurement of body segment parameters using dual energy X-ray absorptiometry and
      three-dimensional geometry: an application in gait analysis.
AB  - Body segment parameters (BSP) are essential input for the computations in
      kinetics of motion applied in the field of biomechanics. These data are usually
      obtained from population-specific predictive equations which present limitations
      in being representative of the population under study. More recently, medical
      imaging techniques have been adopted but are limited to two-dimensional (2-D)
      measurements or required extensive tomographic images for three-dimensional (3-D)
      reconstruction. We proposed an in vivo method to measure 3-D BSP using X-ray
      imaging and 3-D exterior geometry. Criterion values of the BSP were determined
      using magnetic resonance imaging (MRI) which has previously been validated.
      Errors for all BSP values were less than 2% when values derived from our method
      were compared to the criterion values. We found no significant difference between
      our method and four selected BSP models in both stance and swing phase.
      Significant phase effects were observed for our method and other BSP models
      between stance and swing phase. Significant differences (p<0.05) between root
      mean square error (RMSE) ranged from 0.0177 to 0.0234 and 0.0234 to 0.097 Nmkg(
      1) for the knee and hip joints, respectively. However, these BSP variations
      brought about effects on moment output that were less than 0.09 Nmkg(-1). Our
      findings suggest joint kinetic computations during normal gait are relatively
      insensitive to BSP variations. However, the influence of BSP cannot be undermined
      in movements that generate higher acceleration at the limbs. Considering the
      accuracy of our method, it could be used as a novel in vivo method to obtain
      direct 3-D BSP measurements.

PMID- 19106001
TI  - Long-term effect of tibial nerve neurotomy in stroke patients with lower limb
      spasticity.
AB  - OBJECTIVES: We investigated the long-term effects and predictive indices of
      efficacy of tibial nerve neurotomy in a large series of patients with post-stroke
      hemiplegia. METHODS: Fifty-one patients were prospectively included, who showed
      disabling lower limb deformity (equinus, varus, clawing toes). The motor branches
      of the tibial nerve were selected according to the type of deformity, and
      partially resected at the posterior part of the calf. Patients were regularly
      assessed, before surgery and from the third month to the second year post
      surgery, for spasticity (primary outcome measure), motor control, range of active
      and passive movements, balance, walk, gait parameters, Rivermead Motor Assessment
      (RMA), subjective improvement and satisfaction. RESULTS: Neurotomy definitely
      reduced spasticity and improved motor control on antagonist muscles, while
      improving balance, walk, and the RMA. These effects were clearly perceived in
      daily living. A discrete decline was at times observed at 2 years. Functional
      improvement was greater in patients more severely impaired. Side effects,
      consisting in sensory disorders, were observed following neurotomy of the motor
      fascicles of the flexor digitorum longus. CONCLUSIONS: Tibial nerve neurotomy
      showed great and lasting effects, and can be proposed to improve walking and
      balance in stroke patients with disabling lower limb deformity.

PMID- 19106002
TI  - Emission reduction potential of using gas-to-liquid and dimethyl ether fuels on a
      turbocharged diesel engine.
AB  - A study of engine performance characteristics and both of regulated (CO, HC,
      NO(x), and smoke) and unregulated (ultrafine particle number, mass concentrations
      and size distribution) emissions for a turbocharged diesel engine fueled with
      conventional diesel, gas-to-liquid (GTL) and dimethyl ether (DME) fuels
      respectively at different engine loads and speeds have been carried out. The
      results indicated that fuel components significantly affected the engine
      performance and regulated/unregulated emissions. GTL exhibited almost the same
      power and torque output as diesel, while improved fuel economy. GTL significantly
      reduced regulated emissions with average reductions of 21.2% in CO, 15.7% in HC,
      15.6% in NO(x) and 22.1% in smoke in comparison to diesel, as well as average
      reductions in unregulated emissions of total ultrafine particle number (N(tot))
      and mass (M(tot)) emissions by 85.3% and 43.9%. DME can significantly increase
      torque and power, compared with the original diesel engine, as well as
      significantly reduced regulated emissions of 40.1% in HC, 48.2% in NO(x) and
      smoke free throughout all the engine conditions. However, N(tot) for DME is close
      to that for diesel. The reason is that the accumulation mode particle number
      emissions for DME are very low due to the characteristics of oxygen content and
      no C-C bond, which promotes the processes of nucleation and condensation of the
      semi-volatile compounds in the exhaust gas, as a result, a lot of nucleation mode
      particles produce.

PMID- 19106003
TI  - Environmental risk of dissolved oxygen depletion of diverted flood waters in
      river polder systems--a quasi-2D flood modelling approach.
AB  - River polders are retention basins contained by levees alongside rivers into
      which water from the main river channel is diverted during extreme floods in
      order to cap the peak discharge of the flood hydrograph and to alleviate
      downstream flood risk by reducing the water levels. The retained water, however,
      is stagnant and the organic material in the water and the bottom sediments
      imposes a strong oxygen demand on the water. This paper presents a quasi two
      dimensional computer-based methodology to assess the environmental risk exhibited
      by the operation of polders with which the concentration of dissolved oxygen in
      river and polder water can be simulated. A Monte-Carlo analysis allows the
      probability distribution of all the outcomes of the minimum dissolved oxygen
      levels in the water to be derived. From this analysis, the environmental risk of
      the dissolved oxygen concentrations in the polder water falling below 2 mg O2/L
      (the level considered critical for aquatic ecosystems) can be determined. The
      August 2002 extreme flood event on the Elbe River, Germany, with a proposed
      polder system variant was used to calibrate the model. A daily time step was used
      to for the simulations for a time frame 12-21 August 2008. The results show
      plausible spatial and temporal variations in the dissolved oxygen concentrations
      within the polders. The quasi-2D approach was successful in simulating the
      spatial distribution of water quality constituents in the polder system. There is
      up to approximately 20% risk that dissolved oxygen levels fall below 2 mg/L in
      the polders. This risk can potentially increase if sediment oxygen demand
      increases due to crop residue and water temperatures in polders increase. High
      nutrient transport in the river during flooding can cause a spurt of
      phytoplankton growth in the polders.

PMID- 19106004
TI  - Thr715Pro P-selectin polymorphism and P-selectin release in blood obtained from
      the bleeding time wounds in patients with deep-vein thrombosis.

PMID- 19106005
TI  - Metal accumulation and toxicity measured by PAM--chlorophyll fluorescence in
      seven species of marine macroalgae.
AB  - The effects of five metals, copper (Cu), chromium (Cr), Zinc (Zn), cadmium (Cd)
      and lead (Pb), on photosynthetic activity, measured as pulse amplitude modulation
      (PAM) chlorophyll fluorescence yield, was monitored in seven species of green,
      red and brown macroalgae over a 14d period. The 10micromoll(-1) of Cr and Zn
      reduced chlorophyll fluorescence of all species by day 4, and 10micromoll(-1) of
      Cu and Cd reduced the fluorescence of some species; however, fluorescence yields
      of all species were unaffected by 10micromoll(-1) of Pb. Metals were generally
      accumulated in the order of Cu>Pb>Zn>Cr>Cd. Ulva intestinalis accumulated the
      highest amounts of all metals, and Cladophora rupestris the lowest. A
      relationship between internal metal concentration and fluorescence was not always
      evident as in some cases fluorescence was reduced at low metal contents. In the
      case of Zn, fluorescence was lowest in plants which contained lowest
      concentrations after 14d-exposure, possibly because plants had died and Zn
      leached out of the algal cells. The relationship between internal metal
      concentration and fluorescence was algal species and metal-specific.

PMID- 19106007
TI  - A cost-utility analysis of clopidogrel in patients with ST elevation acute
      coronary syndromes in the UK.
AB  - OBJECTIVE: To assess the long-term cost effectiveness of treatment for 1 month,
      and for 1 year with clopidogrel in addition to standard therapy (including
      aspirin) compared with standard therapy alone, in patients diagnosed with ST
      elevation acute myocardial infarction (STEMI) in the UK. DESIGN: Cost utility
      analysis using a cohort Markov model, incorporating clinical data from two
      pivotal clinical trials (the COMMIT/CCS-2 and CLARITY-TIMI 28 trials) and data
      from UK and non-UK observational studies. SETTING: Health economic evaluation
      carried out from the perspective of the UK NHS. PATIENTS: A representative cohort
      of 1000 UK patients aged 60 years, diagnosed with STEMI. INTERVENTIONS: 75 mg/day
      clopidogrel, with and without a 300 mg loading dose, in addition to standard
      therapy (including aspirin, 75-325 mg/day) for 1 month, and for 1 year, followed
      by standard therapy alone for their remaining lifetime, or standard therapy alone
      (including aspirin, 75-325 mg/day) for their remaining lifetime. MAIN OUTCOME
      MEASURES: Incremental cost per quality-adjusted life-year (QALY) gained (ICER).
      RESULTS: For the 1-month treatment option both the COMMIT/CCS-2 and CLARITY-TIMI
      28 trials have ICERs below 2500 pounds. For the 1-year treatment option both
      trials have ICERs below 4000 pounds. Extensive univariate and probabilistic
      sensitivity analyses showed these results to be robust. CONCLUSIONS: In
      combination with previous economic analyses of clopidogrel in NSTEMI patients,
      this paper demonstrates that clopidogrel appears to offer a cost-effective
      treatment option for all ACS patients.

PMID- 19106006
TI  - IL-15 independent maintenance of virus-specific CD8(+) T cells in the CNS during
      chronic infection.
AB  - The role of IL-15 in T cell survival was examined during chronic CNS coronavirus
      infection. Similar numbers of virus-specific CD8(+) T cells were retained in the
      CNS of IL-15(-/-) and wt mice, consistent with loss of IL-2/15 receptor (CD122)
      expression. IL-15 deficiency also had no affect on IL-7 receptor (CD127)
      expression, Bcl-2 upregulation, granzyme B expression, or IFN-gamma secretion in
      CNS persisting CD8(+) T cells. Furthermore, CD8(+) T cell division in the CNS was
      reduced compared to spleen. CD8(+) T cells in the persistently infected CNS are
      thus characterized by IL-15 independent, low level proliferation and an
      activated/memory phenotype.

PMID- 19106008
TI  - Mortality and morbidity of newly diagnosed heart failure treated with statins: a
      propensity-adjusted cohort study.
AB  - BACKGROUND: The effect of treatment with statins on the prognosis of newly
      diagnosed heart failure (ndHF) is not established. We evaluate the relationship
      of commencing treatment with statins (CTS) with the mortality and the morbidity
      of ndHF, systolic (HF-DSF) and non-systolic (HF-PSF). METHODS: Prospective
      propensity-adjusted cohort study over 5 years on 2573 patients with ndHF. The
      main outcomes were all-cause and cardiovascular mortality, hospitalizations and
      visits. We analyze the independent relationship of CTS with the mortality and the
      morbidity, stratifying patients for cardiovascular co-morbidity, after adjusting
      for potential confounders. RESULTS: 1343 patients (52.2%) CTS, 1071 (39.5%) died,
      and 1729 (67.2%) were hospitalized. CTS was associated not only with a lower
      mortality: RR for HF-overall (CI 95%) 0.23 (0.10 to 0.36), RR for HF-PSF 0.34
      (0.21 to 0.47), and RR for HF-DSF 0.20 (0.09 to 0.31), but with dose-dependency
      (statin>20 mg/day vs. statin<=20 mg/day): RR for HF-overall 0.49 (0.33 to 0.67),
      RR for HF-PSF 0.53 (0.39 to 0.70), and RR for HF-DSF 0.37 (0.26 to 0.52), and
      with a lower rate of hospitalization (per 100 persons-year): HF-overall (13.3 vs.
      18.2), HF-PSF (13.9 vs. 19.7), and HF-DSF (12.7 vs. 16.6), (P<0.001 in all
      cases), even after adjustment for the propensity to take statins, or other
      medications, and other potential confounders. CONCLUSION: The commencement of
      treatment with statins is associated with a dose-dependent reduction of the
      mortality and of the morbidity of patients with ndHF (systolic or non-systolic).

PMID- 19106009
TI  - The association between previous statin use and development of atrial
      fibrillation in patients presenting with acute coronary syndrome.
AB  - AIMS: To examine the association between statin use and the development of atrial
      fibrillation (AF) in patients presenting with acute coronary syndrome (ACS).
      METHODS: From a total of 1000 patients presenting with ACS 241 were on and 759
      were not on statin. An AF episode was accepted as endpoint. RESULTS: The
      incidence of AF was less frequent in statin group compared to non-statin group
      (5% vs 10%, respectively, p=0.01). Independent predictors of AF were left atrial
      diameter, use of statin, age, hypertension, previous AF and use of angiotensin
      converting enzyme inhibitors or angiotensin receptor blockers. CONCLUSIONS: In
      ACS patients, statin treatment was associated with lower incidence of AF.

PMID- 19106011
TI  - Axis deviation without left bundle branch block.
AB  - It has been rarely reported changing axis deviation in the presence of left
      bundle branch block also during atrial fibrillation and with acute myocardial
      infarction too. It has also been rarely reported changing axis deviation with
      changing bundle branch block with onset of atrial fibrillation during acute
      myocardial infarction. We present a case of axis deviation without left bundle
      branch block and without atrial fibrillation and acute myocardial infarction in a
      65-year-old Italian man. To our knowledge, this is the first report of axis
      deviation without left bundle branch block and without atrial fibrillation and
      acute myocardial infarction.

PMID- 19106010
TI  - Clinical features of and effects of angiotensin system antagonists on amiodarone
      induced pulmonary toxicity.
AB  - BACKGROUND: Amiodarone (AMD) is a strong antiarrhythmic drug but has severe side
      effects such as pulmonary toxicity. There are no indicators or drugs that can
      prevent the development of amiodarone-induced pulmonary toxicity (AIPT). METHODS:
      We collected data for 96 consecutive patients treated with AMD and analyzed
      clinical factors related to AIPT. In addition, we examined the effect of AMD and
      angiotensin II (Ang II) on human lung alveolar epithelial cells (AEC) and
      verified the protective efficacy of an Ang II type 1 receptor blocker (ARB) in
      vitro. RESULTS: During a follow-up period of 33.8+/-34.6 months, AIPT developed
      in 11 patients (11.5%). There were no differences in the dose of AMD, left
      ventricular ejection fraction, serum KL-6 and %DLCO level before starting AMD
      between patients with and those without AIPT. However, repeated episodes of
      congestive heart failure (CHF) were observed more frequently in patients with
      AIPT than in patients without AIPT (81.8% vs. 41.2%, P<0.011). In vitro
      examination, AMD progressively increased apoptosis of AEC and Ang II enhanced
      this effect of AMD (P<0.001). However, ARB inhibited the enhancement by Ang II of
      the AMD-induced apoptosis effect (P<0.001). Furthermore, patients with AIPT were
      administrated a lower dose of angiotensin system antagonists than were those
      without AIPT (P<0.05). CONCLUSIONS: The results indicate that Ang II induced by
      CHF increases the risk of AMD-induced pulmonary toxicity. An angiotensin
      converting enzyme inhibitor or ARB should be given at a sufficient dose during
      AMD treatment.

PMID- 19106012
TI  - Anemia and renal failure as predictors of risk in a mainly non-ischemic heart
      failure population.
AB  - Anemia and renal failure (RF) are related to poor prognosis in chronic heart
      failure (HF). Anemia appear early in the course of RF and its value as predictor
      of risk in HF may be overlap by the value of RF. We aimed to establish the
      prognostic value of anemia and RF in a Brazilian HF population.

PMID- 19106013
TI  - Detection of Vibrio parahaemolyticus in tropical shellfish by SYBR green real
      time PCR and evaluation of three enrichment media.
AB  - A rapid, sensitive and highly reproducible SYBR green based real-time PCR assay
      was developed for detection of tdh positive pathogenic Vibrio parahaemolyticus.
      Minimum detection limit was 0.1 pg of pure V. parahaemolyticus genomic DNA with
      typical R(2) values >0.99 and coefficient of variation (CV) values ranging from
      1.2 to 4.2 on three different days. The method was also used to evaluate the
      effect of three different enrichment media alkaline peptone water (APW), sodium
      taurocholate (ST) broth and salt polymyxin broth (SPB) on detection of V.
      parahaemolyticus. Crude lysates were directly used for real-time PCR. Without
      enrichment, the detection limit of pure cultures was 10(1) CFU/ml for ST broth
      and 10(2) CFU/ml in APW and SPB but for shrimp homogenates spiked with pure
      culture, the minimum detection limit was 10(2) CFU/ml for all three broths with a
      linear detection range of 10(2)-10(6). Without enrichment, detection in ST broth
      was more efficient than APW and SPB. After 6 h enrichment, limit of detection was
      found to be 1 CFU in all three media. However, for iced shrimp, the limit of
      detection was 10(2) after 6 h enrichment. No significant difference was seen
      between different enrichment media with respect to tdh gene detection of V.
      parahaemolyticus. The methodology developed here can be useful for rapid
      detection of tdh positive V. parahaemolyticus by laboratories involved in
      monitoring programmes for pathogenic V. parahaemolyticus.

PMID- 19106014
TI  - Detection of total and pathogenic Vibrio parahaemolyticus in shellfish:
      comparison of PCR protocols using pR72H or toxR targets with a culture method.
AB  - PCR protocols directly applied to enrichment broth cultures were compared with a
      culture method based on the ISO reference for detection of Vibrio
      parahaemolyticus in 57 natural bivalve mollusc samples. Comparisons were made on
      different primer pairs specifically targeting the V. parahaemolyticus-specific
      toxR gene (Vp-toxR) and pR72H fragment, and also tdh and trh hemolysin genes. The
      PCR method using these different primer pairs and the culture method were also
      examined for their limits of detection (LOD). The LODs ranged from 7-24 pg of
      purified DNA per reaction tube (RT) for primer pair Vp-toxR, but for primer pair
      pR72H, varied greatly depending on the V. parahaemolyticus strains used (0.7 pg
      10.6 ng/RT). The Vp-toxR and pR72H primers allowed the detection of V.
      parahaemolyticus in 25 and 8 out of the 57 samples, respectively, while only 3 V.
      parahaemolyticus-positive samples were obtained by the culture method. The
      effective presence of V. parahaemolyticus in the Vp-toxR-positive samples was
      confirmed by sequencing the PCR products. The trh and Vp-toxR genes were
      simultaneously detected in 14% of the samples, which were thus considered as
      presumptively contaminated with pathogenic V. parahaemolyticus. These results
      emphasize the need for an efficient survey of both the total and pathogenic V.
      parahaemolyticus present in seafood in France. The PCR protocol targeting Vp-toxR
      followed by tdh and trh genes is an efficient and reliable method for the
      detection of total and presumptively pathogenic V. parahaemolyticus in bivalve
      molluscs.

PMID- 19106015
TI  - Senescence of aerial parts is impeded by exogenous gibberellic acid in herbaceous
      perennial Paris polyphylla.
AB  - The effects of gibberellin A(3) (GA(3)) on natural senescence and the
      relationship between gibberellins (GAs), abscisic acid (ABA), and senescence are
      not fully understood. For example, it is still unclear whether GA and ABA act
      antagonistically. There are only few reports on senescence-related changes in
      physiological parameters of herbaceous perennials. This study was designed to
      investigate the effects of exogenous GA(3) on the senescence of aerial parts in a
      herbaceous perennial species, Paris polyphylla, and to test the hypothesis that
      GA and ABA display antagonistic effects in this process. Physiological changes
      associated with senescence, in particular of the hormonal and oxidative
      metabolisms, were also investigated. GA(3) was sprayed on mature leaves at weekly
      intervals, which significantly impeded senescence of aerial parts and slowed the
      decline of pigments and total soluble protein. Treated plants suffered less
      oxidative stress as revealed by reduced lipid peroxidation, a lower hydrogen
      peroxide level and modified activities of superoxide dismutase, peroxidase,
      ascorbate peroxidase, and their respective isozyme profiles. In GA(3) treated
      plants GA(4)+GA(7) (GAs) levels increased progressively and became significantly
      higher than those of control plants, whereas ABA increased in controls. When
      plants were treated with GA-synthesis inhibitor paclobutrazol (PCB), GAs
      decreased, ABA increased, and senescence was promoted. Application of a mixture
      of GA(3) and PCB restored the accumulation of GAs, reduced ABA, and ultimately
      senescence was delayed. These results suggest that GA and ABA play antagonistic
      roles in the senescence of aerial parts in P. polyphylla, and this process is
      associated with oxidative stress and regulated by endogenous hormones and
      extrinsic factors. Possible mechanisms that control this GA(3)-mediated
      inhibition of senescence are discussed.

PMID- 19106016
TI  - A transcriptional profile of metallophyte Viola baoshanensis involved in general
      and species-specific cadmium-defense mechanisms.
AB  - Viola baoshanensis Shu, Liu et Lan is a newly identified metallophyte, and its
      defensive strategies against heavy metals are still unclear. In the present
      study, we firstly constructed a root cDNA library of the plant subjected to
      300muM Cd for 48h by using suppression subtractive hybridization (SSH), and 43
      unique cDNA fragments were further isolated from the library. Sequence homology
      analysis showed that half of the identified genes were involved in general stress
      defense, such as antioxidative enzymes, protein degradation and stress signal
      transduction. After RT-PCR and RACE analysis, a Cd-responsive gene Vb40 was
      identified, which could deduce a novel cysteine-rich mini-protein. Meanwhile,
      five cyclotide precursor genes (VbCP1-VbCP5) were also identified. The Vb40 and
      the VbCP1-VbCP5 were further investigated by yeast expression analysis, and they
      could improve copper (Cu) tolerance in hosted yeast, indicating that these
      species-specific genes possibly functioned in V. baoshanensis heavy metals
      tolerance. Our results suggested that heavy metal tolerance in V. baoshanensis
      relied on both general and species-specific defense.

PMID- 19106017
TI  - Transcript profiling of the salt-tolerant Festuca rubra ssp. litoralis reveals a
      regulatory network controlling salt acclimatization.
AB  - We report an analysis of salt-stress responses in the monocotyledonous halophyte
      Festuca rubra ssp. litoralis. Salt-dependent expression of transcripts encoding a
      PIP2;1 aquaporin, V-ATPase subunit B, and the Na+/H+ antiporter NHX was
      characterized. Transcription of FrPIP2;1, FrVHA-B, and FrNHX1 was induced in root
      tissue of F. rubra ssp. litoralis by salt treatment, and during salt-stress F.
      rubra ssp. litoralis accumulated sodium in leaves and roots. Cell specificity of
      FrPIP2;1, FrVHA-B, and FrNHX1 transcription was analyzed by in situ PCR in roots
      of F. rubra ssp. litoralis. Expression of the genes was localized to the root
      epidermis, cortex cells, endodermis, and the vascular tissue. In plants treated
      with 500 mM NaCl, transcripts were repressed in the epidermis and the outer
      cortex cells, whereas endodermis and vasculature showed strong signals. These
      data demonstrate that transcriptional regulation of the aquaporin PIP2;1, V
      ATPase, and the Na+/H+ antiporter NHX is correlated with salt tolerance in F.
      rubra ssp. litoralis and suggests coordinated control of ion homeostasis and
      water status at high salinity in plants. Salt-induced transcript accumulation in
      F. rubra ssp. litoralis was further monitored by cDNA-arrays with expressed
      sequence tags derived from a cDNA subtraction library. The salt-regulated
      transcripts included those involved in the control of gene expression and signal
      transduction elements such as a serine/threonine protein kinase, an SNF1-related
      protein kinase, and a WRKY-type transcription factor. Other ESTs with salt
      dependent regulation included transcripts encoding proteins that function in
      metabolism, general stress responses, and defense and transport proteins.

PMID- 19106018
TI  - Upper urothelial carcinoma in Balkan endemic nephropathy and non-endemic regions:
      a comparative study of pathological features.
AB  - Upper urothelial carcinoma (UUC), a rare neoplasm, occurs more frequently in some
      regions of Balkan countries than in other areas in the world. The aim of this
      study is to compare phenotypic morphological characteristics of UUC in Balkan
      endemic nephropathy (BEN) region and control rural and city populations free of
      BEN, and to determine the characteristic(s) that could discriminate tumors in
      endemic and non-endemic regions. The authors analyzed biopsies from 88 patients
      with UUC, 40 patients who live in Balkan endemic (BEN) settlements and 48 control
      subjects. The histological sections were used to assess morphological variables:
      histologic grade, pathologic stage (pT), growth pattern, pattern of invasion,
      lympho-vascular invasion (LVI), presence of necrosis and metaplastic changes
      (squamous or glandular) within the tumor. Statistically significant differences
      between the groups were found concerning tumor grade, pattern of invasion, growth
      pattern and metaplastic changes. High-grade tumors and trabecular/infiltrative
      patterns of invasion were more frequent in the group of BEN tumors (chi(2)=4.583,
      p<0.05; chi(2)=8.064, p<0.05). Moreover, solid growth and metaplastic changes are
      significant in BEN tumor, chi(2)=9.696, p<0.01; chi(2)=9.35, p<0.01,
      respectively. Discriminant analysis of morphological variables had indicated that
      BEN and control tumors are significantly different (Wilks' lambda=0.833,
      chi(2)=15.044 and p<0.05). The best characteristic that differentiated them was
      growth pattern; i.e., solid growth for BEN tumors and papillary for control
      tumors.

PMID- 19106019
TI  - Saturation biopsy improves preoperative Gleason scoring of prostate cancer.
AB  - We evaluated the differences between conventional needle biopsy (CB) and
      saturation biopsy (SB) techniques with regard to the prediction of Gleason score,
      tumor stage, and insignificant prostate cancer. Data from a total number of 240
      patients were analyzed. The main group, consisting of 185 patients, was diagnosed
      according to a saturation prostate needle biopsy protocol (SB), by which more
      than 12 cores were taken per biopsy. The control group was diagnosed using CB, by
      which 12 or less than 12 cores were taken per biopsy (n=55). In the main group,
      the Gleason score of the biopsy was confirmed in 19.5%, in the control group in
      23.5% according to the prostatectomy specimen (p=0.50). Upgrading after the
      operation was found in 56.7% in the main group and in 60% in the control group
      (p=0.24). Downgrading after the operation was found in 23.9% in the main group
      and in 16.3% in the control group (p=0.24). If the Gleason score of the
      postoperative specimens differed by only one point from the biopsy, we considered
      this a minor deviation. In the main group, 59% of the carcinomas were
      preoperatively classified correctly or revealed minor deviation in Gleason
      scores. In contrast, only 47% of the carcinomas in the control group were
      assessed correctly or with minor deviation in Gleason scores. Thus, the main
      group demonstrated a better rate of preoperative prediction in tumor grading
      assessed by Gleason score (p=0.05). In addition, the Gleason scores of both
      protocols were assigned to three groups (Gleason <7; Gleason 7; Gleason >7), and
      the group changes from the biopsy to the prostatectomy specimen were found to be
      significantly more frequent in the CB group (p=0.04). There was no significant
      difference between the two types of biopsy techniques regarding tumor stage or
      the detection of insignificant carcinomas. The advantage of the extensive
      prostate needle biopsy technique (SB) is a better preoperative prediction of the
      Gleason score as well as the risk groups with Gleason scores <7, equal to 7, or
      >7. Both techniques fail to detect insignificant prostate cancer.

PMID- 19106020
TI  - Crystal-storing histiocytosis associated with only one of two consecutive, but
      genetically unrelated B-cell lymphomas.
AB  - A localized crystal-storing histiocytosis (CSH) making the underlying marginal
      zone lymphoma (MZL) hardly discernible microscopically is described. Image
      analysis of the hyper electron dense crystals localized light microscopically in
      swollen histiocytic cells exhibited a major equatorial periodicity of 6.6 nm.
      Rarely, crystals of this type were detected within plasma cells, but were always
      surrounded by smooth membrane in contrast to Russell bodies. IgM/lambda
      restriction and VH3-21*02, DH4-17*01, JH4*02 gene usage were detected behind the
      lesion. Within 26 months, a genetically unrelated lymphoma of CD5-CD20-CD23
      positive phenotype with a different VH1-24*01, DH2-21*02, JH2*01 heavy chain
      rearrangement, but with the same light chain gene usage, was identified without
      CSH. This might indicate that the unique condition responsible for the crystal
      formation is likely to rely on the sequence of the first clonally rearranged
      heavy chain exhibiting much higher CDRIII pI value (6.0) than the average.

PMID- 19106021
TI  - Positive contrast visualization for cellular magnetic resonance imaging using
      susceptibility-weighted echo-time encoding.
AB  - OBJECTIVE: The objective of this study was to investigate a method to generate
      positive contrast, selective to superparamagnetic iron oxide (SPIO) labeled
      cells, using the susceptibility-weighted echo-time encoding technique (SWEET).
      MATERIALS AND METHODS: SPIO-labeled human epidermal carcinoma (KB) cells were
      placed in a gel phantom. Positive contrast from the labeled cells was created by
      subtraction between conventional spin-echo images and echo-time shifted
      susceptibility-weighted images. SPIO-labeled cells were injected into the left
      dorsal flank and hind limb of nude mice, and unlabeled cells were placed on the
      right side as controls. Tumor growth was monitored using the proposed method, and
      a histological analysis was used to confirm the presence of the labeled cells.
      RESULTS: Based on in vitro testing, we could detect 5000 labeled cells at minimum
      and the number of pixels with positive contrast increased proportionally to the
      number of labeled cells. Animal experiments also revealed the presence of tumor
      growth from SPIO-loaded cells. CONCLUSIONS: We demonstrated that the proposed
      method, based on the simple principle of echo-time shift, could be readily
      implemented in a clinical scanner to visualize the magnetic susceptibility
      effects of SPIO-loaded cells through a positive-contrast mechanism.

PMID- 19106022
TI  - Nuclear magnetic resonance microimaging investigation of membrane electrode
      assembly of fuel cells: morphology and solvent dynamics.
AB  - The structure and solvent (water, methanol, etc.) dynamics of a number of fuel
      membrane electrode assembly (MEA) samples are studied with nuclear magnetic
      resonance microimaging with spatial resolution of tens of micrometers. The
      micrometer-scale inhomogeneity of the samples is observed and confirmed with
      various weighting methods. In particular, diffusion coefficients at different
      positions in MEA are clearly differentiated. Furthermore, chemical shift
      selection imaging enables one to investigate the spatial distribution and
      dynamics of individual chemical groups. These types of information offer us
      insights into the working principle of fuel cell and pave the way to in situ
      studies of operating fuel cells.

PMID- 19106023
TI  - Damages to the extracellular matrix in articular cartilage due to
      cryopreservation by microscopic magnetic resonance imaging and biochemistry.
AB  - To investigate the damages to the extracellular matrix in articular cartilage due
      to cryopreservation, the depth-dependent concentration profiles of
      glycosaminoglycans (GAGs) in 34 cartilage specimens from canine humeral heads
      were imaged at 13-mum pixel resolution using the in vitro version of the dGEMRIC
      protocol in microscopic MRI (microMRI). In addition, a biochemical assay was used
      to determine the GAG loss from the tissue to the solution where the tissue was
      immersed. For specimens that had been frozen at -20 degrees C or -80 degrees C
      without any cryoprotectant, a significant loss of GAG (as high as 56.5%) was
      found in cartilage, dependent upon the structural zones of the tissue and the
      conditions of cryopreservation. The cryoprotective abilities of dimethyl
      sulfoxide (DMSO) as a function of its concentration in saline and storage
      temperature were also investigated. A 30% DMSO concentration was sufficient in
      preventing the reduction of GAG in the tissue at the -20 degrees C storage
      temperature, but a 50% concentration of DMSO was necessary for the -80 degrees C
      cryopreservation. These imaging results were verified by the biochemical
      analysis.

PMID- 19106024
TI  - Dynamic half-Fourier single-shot turbo spin echo for assessment of deep venous
      thrombosis: initial observations.
AB  - OBJECTIVE: The objective of this study was to retrospectively analyze the value
      of dynamic half-Fourier single-shot turbo spin echo (HASTE) imaging in patients
      with suspected deep venous thrombosis (DVT). MATERIALS AND METHODS: Fifty-five
      veins in 24 patients were interrogated using a HASTE sequence with the patients
      relaxed and in various degrees of Valsalva. Veins were analyzed for changes in
      caliber (+CAL) and signal intensity (+SI) or in their absence (-CAL and -SI,
      respectively) and compared with the presence of thrombus on gadolinium-enhanced
      magnetic resonance imaging. RESULTS: There was no thrombus in veins with the
      +CAL, +SI pattern (n=40) (P<.01). Five of seven veins (71.4%) with the -CAL, -SI
      pattern had thrombus (P<.01). A qualitative change in CAL had a sensitivity of
      100% and a specificity of 91% for the presence of thrombus. An increase of 1.5 mm
      in CAL had a sensitivity of 100% and a specificity of 93% for this diagnosis.
      CONCLUSION: Dynamic HASTE imaging offers a physiological method to evaluate veins
      for deep venous thrombosis.

PMID- 19106025
TI  - Association between visual degeneration of intervertebral discs and the apparent
      diffusion coefficient.
AB  - The value of apparent diffusion coefficient (ADC) measurements in intervertebral
      disc has been studied because ADC provides an estimate of free diffusion of
      unbound water and could be used as a quantitative tool to estimate degenerative
      changes. However, the challenging nature of diffusion imaging of spine and
      limited numbers of subjects in earlier studies has produced contradictory
      findings. We aimed to determine the relation between ADC and visual degenerative
      changes in lumbar intervertebral discs in a sufficiently large homogeneous study
      group. Lumbar spines of 228 volunteer middle-aged men were MR imaged at 1.5 T
      including anatomic and diffusion-weighted imaging. ADC values, T2 signal
      intensity and height, and width of the three lowest lumbar intervertebral discs
      were measured and disc degeneration visually graded. The calculated average ADC
      of 530 measured discs was 2.01 x 10(-3) mm(2)/s+/-0.29 (+/-S.D.). The reduction
      in ADC between visually normal and moderately degenerated discs was 4%. Severely
      degenerated discs showed 5% larger ADC values than normal discs, presumably due
      to free water in cracks and fissures of those discs. T2 signal intensity of the
      disc was significantly correlated with the ADC values, whereas other measured
      parameters did not show correlation. There was no evident difference in ADC
      between the studied anatomic lumbar levels. Because there is considerable overlap
      between ADC values of normal and degenerated discs, we conclude that ADC
      measurements of intervertebral discs, at least with current technology, have
      limited clinical value.

PMID- 19106026
TI  - Arthroscopic treatment of patellar clunk and synovial hyperplasia after total
      knee arthroplasty.
AB  - Patellofemoral pain, crepitus, and locking are infrequent symptoms after total
      knee arthroplasty (TKA). We performed a retrospective review of 25 patients who
      underwent arthroscopic debridement after primary TKA to treat the patellar clunk
      syndrome (15 knees) or patellofemoral synovial hyperplasia (10 knees). After
      surgery, patient-reported knee pain and crepitus as well as Knee Society knee and
      function scores improved in both groups. Postoperative knee range of motion
      remained unchanged. Arthroscopic debridement of symptomatic patellofemoral
      synovium after TKA is a safe and effective procedure.

PMID- 19106027
TI  - Activity scale for arthroplasty patients after total hip arthroplasty.
AB  - The purpose of the Activity Scale for Arthroplasty Patients (ASAP) is to develop
      and validate a self-report questionnaire that demonstrated discrimination of
      functional gains, low burden, appropriate concurrent validity, and was not
      limited by ceiling effects. We identified 128 high-functioning hip arthroplasty
      patients from our database who completed a 25-item ASAP and Lower Extremity
      Functional Scale questionnaires and a set of anchor questions. Factor analysis
      identified 10 items associated with 2 distinct factors: (1) activities and (2)
      running and running-related environments. These 10 items were retained and were
      identified as the ASAP. The ASAP may be useful in high-level hip arthroplasty
      patients where other scales fail to capture activities secondary to ceiling
      effects. In addition, the scale burden is minimized by inclusion of only 10
      items.

PMID- 19106028
TI  - Risk factors for perioperative mortality after lower extremity arthroplasty: a
      population-based study of 6,901,324 patient discharges.
AB  - The goal of this study was to provide nationally representative data on
      characteristics of patients who died after hip and knee arthroplasty and to
      determine risk factors for such outcome. Using national in-patient data collected
      between 1990 and 2004, we identified a cumulative in-hospital mortality rate of
      0.35% among an estimated 6,901,324 procedures. The strongest independent risk
      factors for in-hospital mortality were pulmonary embolism and cerebrovascular
      complications, which increased the odds for a fatal outcome by approximately 40
      fold. Preoperative risk factors for in-hospital mortality were revision total hip
      arthroplasty, advanced age, and the presence of a number of comorbid diseases,
      predominantly dementia, renal, and cerebrovascular disease. Our results can be
      used to identify patients at risk for fatal outcome and implement interventions
      to reduce such risk.

PMID- 19106029
TI  - The effect of total hip arthroplasty on employment.
AB  - This study was undertaken to investigate the impact of total hip arthroplasty on
      a patient's work ability. Fifty-four patients who were in the workforce completed
      a questionnaire 1 year after total hip arthroplasty. Thirty-eight (86%) of 44
      patients working preoperatively were working 1 year after surgery, whereas only 2
      (20%) of 10 patients who were not working preoperatively resumed work. Those who
      resumed work were younger and reported better Oxford-12 and physical function
      scores. Patients who resumed working had improvements in their ability to meet
      workplace physical demands and in productivity. Total hip arthroplasty has
      positive effects on work capacity in patients who return to work. To help
      patients remain in the workforce, surgery should be undertaken before a patient's
      hip dysfunction forces them off work.

PMID- 19106030
TI  - Achieving deep flexion after primary total knee arthroplasty.
AB  - Total knee arthroplasty patients often have difficulty performing activities
      involving flexion beyond 130 degrees. The NexGen LPS Flex (Zimmer Inc, Warsaw,
      Ind) mobile bearing implant accommodates up to 155 degrees of flexion. Two
      hundred eighteen total knee arthroplasties were performed using this implant on
      125 patients over a 2-year period with a minimum of 5 years follow-up. All data
      were collected prospectively. Forty-four percent of preoperative cases had full
      flexion (ie, 140 degrees active flexion and ability to kneel with thigh/calf
      contact for 1 minute). Five-year data showed an average flexion of 140 degrees +/
      11.5 degrees and flexion greater than 140 degrees in 103 knees (68%). There were
      no differences in patellofemoral pain levels, complications, or Knee Society
      scores despite our patients having, on average, an increase in flexion and
      function.

PMID- 19106031
TI  - Total knee arthroplasty for arthritic knees with tibiofibular stress fractures:
      classification and treatment guidelines.
AB  - Forty-two tibial and 5 fibular stress fractures in 34 patients with knee
      arthritis were radiologically classified into intraarticular malunited and
      ununited fractures, and extraarticular impending, acute, united, malunited, and
      ununited fractures. Depending on fracture type, total knee arthroplasty was
      performed using long-stem tibial component, metal augments, corrective osteotomy,
      or in routine fashion. At a mean follow-up of 36 months, the mean Knee Society
      knee score improved from 36.7 points preoperatively to 90.3 points; function
      score improved from 24 to 86.2 points. All fractures had united at the last
      follow-up with no complications of infection, joint instability, and patellar
      problems. Total knee arthroplasty for knee arthritis in the presence of
      tibiofibular stress fractures restores limb alignment and facilitates fracture
      healing with excellent functional outcome.

PMID- 19106032
TI  - Interpretations of the clinical outcomes of the nonresponders to mail surveys in
      patients after total knee arthroplasty.
AB  - This study examined whether or not nonresponders to mail survey have poorer
      clinical outcomes than responders. A postal questionnaire, which was designed to
      evaluate the functional disability and patient's satisfaction, was mailed to 387
      patients whose 1-year clinical outcomes were available. Of the 270 patients
      (69.8%) who responded, 247 (91.4%) reported that they were satisfied with their
      replaced knees. The knees of the nonresponders showed significantly poorer
      results in terms of the function-related scales (American Knee Society score
      function, Western Ontario McMaster University Osteoarthritis Index scale
      function, Short-Form 36 physical and functional scores) than the knees of the
      responders, whereas there were no significant differences in the pain-related
      scales. The clinical results of the nonresponders were poorer in most of the
      clinical outcome scales than those of the satisfied subgroup of responders but
      better than those of the dissatisfied subgroup. The results of the pain-related
      scales were similar to the satisfied subgroup but the function-related scales
      were similar to the dissatisfied subgroup.

PMID- 19106033
TI  - A navigated 8-in-1 femoral cutting guide for total knee arthroplasty technical
      development and cadaveric evaluation.
AB  - The goals of this study were to determine the precision of femoral component
      placement using a novel computes assisted surgery (CAS)-enabled 8-in-1 cutting
      guide in cadaver limbs and to identify errors generated at various stages of the
      cutting process. The cutting guide placement was on average within 1 degrees or
      millimeter of the target position in the varus/valgus, axial rotation, and cut
      height directions and within 2 degrees or millimeters, in all other directions.
      The difference between the desired femoral component and the impacted trial
      component position, defined as the execution error, averaged 0.9 degrees +/- 1.7
      degrees of varus rotation, 0.8 +/- 2.3 mm of lateral translation, and 0.3 +/- 1
      mm of proximal translation in the coronal plane (+/-SD). In the sagittal and
      axial planes, the execution error averaged 2.8 degrees +/- 2.5 degrees of
      flexion, 3.4 +/- 1.3 mm of anterior translation, and 0.7 degrees +/- 2.7 degrees
      of external rotation. CAS permits accurate placement of 8-in-1 jigs for
      valgus/varus, axial rotation, and cut height but is less accurate in the sagittal
      plane. Care should be taken when executing the cuts, which can affect precision
      in the sagittal plane more than actual positioning of the jig.

PMID- 19106034
TI  - Neuroleptic effects on P50 sensory gating in patients with first-episode never
      medicated schizophrenia.
AB  - Sensory gating deficit, as reflected by P50 suppression, has been demonstrated in
      schizophrenia. Despite extensive evidence of the irreversible effects of typical
      neuroleptics on this deficit, recent studies of atypical neuroleptics have
      produced inconsistent findings on the reversibility of P50 suppression in
      schizophrenia. As the majority of these studies were limited by either their
      cross-sectional design or the recruitment of patients on multiple medications,
      the current study was designed to examine the effects of different neuroleptic
      medications on the P50 sensory gating index in patients with first-episode, never
      medicated schizophrenia. P50-evoked potential recordings were obtained from 62
      normal controls when they entered the study and from 65 patients with first
      episode, never-medicated schizophrenia at baseline and after six weeks of
      different neuroleptic treatments (sulpiride [n=24], risperidone [n=24] and
      clozapine [n=17]). The first-episode, never-medicated schizophrenia patients had
      impaired sensory gating relative to the normal controls (mean=94.19% [SD=61.31%]
      versus mean=41.22% [SD=33.82%]). The test amplitude S2 was significantly higher
      in the schizophrenia patients than in the normal controls. The conditioning
      amplitude S1 and the positive symptom scores were related to the P50 gating
      ratios in schizophrenia at baseline. There was no change in P50 sensory gating
      (P>0.10) and a significant improvement in the clinical ratings (P>0.10) after six
      week neuroleptic treatment for schizophrenia. P50 sensory gating was not
      significant for the patients who received sulpiride, risperidone or clozapine at
      baseline (F=1.074, df=2, 62, P=0.348) or at endpoint (F=0.441, df=2, 62,
      p=0.646). Our findings indicate that there is P50 sensory gating impairment in
      first-episode, never-medicated schizophrenia and that treatment with typical and
      atypical antipsychotics has no significant impact on such gating in this illness.

PMID- 19106035
TI  - Dose trends for second-generation antipsychotic treatment of schizophrenia and
      bipolar disorder.
AB  - BACKGROUND: Antipsychotic dosing used in clinical practice can differ from dosing
      originally recommended in product labeling. This has been reported for olanzapine
      and quetiapine, where higher doses are commonly used. This may be the case for
      ziprasidone as well. METHOD: To characterize changes over time in dosing for the
      initial and subsequent prescriptions of first-line second-generation
      antipsychotics used during treatment episodes for outpatients with schizophrenia
      and bipolar disorder, the 2001-2005 Thomson MarketScan Medicaid Database
      (Medicaid) and the 2001-2006 MarketScan Commercial Claims and Encounters Database
      (Commercial) were analyzed. Dose trends were evaluated using autoregressive time
      series models. RESULTS: Data were available for 49180 treatment episodes of
      schizophrenia (4683 Commercial and 44497 Medicaid) and 83289 treatment episodes
      of bipolar disorder (57961 Commercial and 25328 Medicaid). The initial
      prescription mean daily and overall mean daily doses of ziprasidone in
      schizophrenia episodes significantly increased across the Medicaid and Commercial
      populations, with similar trends observed for bipolar episodes. The first (May
      2001) and last (December 2005) observed 3-month mean daily doses for ziprasidone
      were 112 mg/d and 138 mg/d for patients with schizophrenia and 93 mg/d and 113
      mg/d for those with bipolar disorder in the Medicaid cohort, with similar
      findings for the Commercial cohort. Consistently significant trends in dose
      changes were not observed for the other medications, although quetiapine and
      olanzapine doses generally increased while aripiprazole and risperidone doses
      generally decreased. CONCLUSIONS: There remains a need for controlled randomized
      clinical trials that test fixed doses of antipsychotics to ascertain the dose
      response relationship within the dose range used in contemporary clinical
      practice.

PMID- 19106036
TI  - Hand-preference and population schizotypy: a meta-analysis.
AB  - Language functions in schizophrenia patients are represented more bilateral, i.e.
      less lateralized than in healthy subjects. This decreased lateralization is also
      observed in individuals at increased risk for schizophrenia. Language
      lateralization is related to handedness; in that left- and mixed-handed
      individuals more frequently have decreased lateralization in comparison to right
      handed subjects. Population schizotypy can be considered part of the
      schizophrenia spectrum disorders. In line with this, population schizotypy has
      repeatedly, though inconsistently, been associated with left-handedness. In order
      to define the exact association between handedness and schizotypy, we performed
      meta-analyses on the available literature. We found that non-right-handed
      subjects, but not strong left-handers, had higher scores on schizotypy
      questionnaires than right-handed subjects. Mixed-handers showed a trend towards
      higher schizotypy in comparison to strong left-handers. It is argued that the
      higher schizotypy in non-right-handed individuals reflects the higher incidence
      of bilateral language lateralization in this group. Bilateral language
      organisation may underlie loosening of association, possibly leading to higher
      schizotypy scores.

PMID- 19106037
TI  - Lipid-lowering effects of polydatin from Polygonum cuspidatum in hyperlipidemic
      hamsters.
AB  - Hyperlipidaemias are common in obese people, and they increase the risk of
      cardiovascular diseases such as coronary heart disease (CHD) and atherosclerosis
      (AS). Previous studies have shown that several drugs can depress serum
      cholesterol. However, they could cause serious side effects in various clinical
      settings. The objective of the present study was to evaluate the lipid-lowering
      effects of polydatin in high-fat/cholesterol (HFC)-fed hamsters. The levels of
      lipids in hamsters were measured enzymatically before and after the
      administration of polydatin. Significant differences between HFC and
      HFC+polydatin were detected for those concentrations. Decreased levels of serum
      TC, TG and LDL-C and the concentrations of hepatic TG were found. Experimental
      results also showed that polydatin elevated LDL-C/HDL-C and TC/HDL-C ratios. In
      concert with other effects, serum cholesterol-lowering effect in hamsters may
      contribute to the regulation properties attributed to polydatin.

PMID- 19106038
TI  - Nitric oxide and carbon monoxide synthesizing enzymes and soluble guanylyl
      cyclase within neurons of adult human cardiac ganglia.
AB  - Nitric oxide and carbon monoxide are diffusible gas messengers, synthesized by
      nitric oxide synthase or heme oxygenase 2, respectively, that can activate
      soluble guanylyl cyclase in adjacent cells. Nitric oxide and carbon monoxide
      neuromodulation in cardiac ganglia has been demonstrated. However, identification
      of nitric oxide or carbon monoxide in human cardiac ganglia needs to be confirmed
      as suggested from animal model studies. Immunohistochemistry was used to
      demonstrate neuronal nitric oxide synthase, heme oxygenase 2, and soluble
      guanylyl cyclase immunoreactivity within neurons of adult human cardiac ganglia.
      Nitric oxide synthase immunoreactivity was present in 37% of neurons within
      cardiac ganglia, heme oxygenase 2 immunoreactivity in 79%, and soluble guanylyl
      cyclase in 53%. Our findings support the hypothesis that nitric oxide and carbon
      monoxide are modulators of neurotransmission in cardiac ganglia and in neural
      control of the adult human heart.

PMID- 19106039
TI  - Evolution of three dimensional skin equivalent models reconstructed in vitro by
      tissue engineering.
AB  - Since the culture of keratinocytes on feeder layers, research to produce skin
      equivalents has been motivated by the challenge of treating large burns and
      chronic wounds and by European regulations which both require proof of the
      innocuousness and the effectiveness of cosmetic products, and which forbid animal
      testing. The dynamism in fundamental research, dermocosmetology and the
      pharmaceutical industry has led to the evolution and complexification of
      reconstructed skin. The Collagen-GAG-Chitosan sponge, as well as the self
      assembly model, allow dermal reconstruction in which the neosynthesized
      extracellular matrix contains all of the desired macromolecules. It is deposited
      forming an ultrastructurally organised architecture. The quality of the dermis
      obtained allows the development and regeneration of a pluristratified and
      differentiated epidermis firmly anchored by an organised dermal-epidermal
      junction. Evolution of reconstructed skin into models which are more and more
      similar to the physiological skin results in higher graft take rates in the
      treatment of burns and chronic wounds, and brings to research, to
      dermocosmetology and to the pharmaceutical industry, a wide range of products
      such as pigmented, endothelialized, immunocompetent, and now adipose
      reconstructed skins. The present review will mainly concentrate on the latest
      developments in skin engineering and will mostly concern the studies carried out
      by our groups.

PMID- 19106040
TI  - Xeroderma pigmentosum: neck lymph node metastasis of a squamous cell carcinoma of
      the skin treated with cetuximab.
AB  - Xeroderma pigmentosum is a genodermatosis characterized by defects in the DNA
      nucleotide excision repair pathway, which increases the risk of suffering skin
      cancers. There is lack of information about the efficacy and toxicity of
      chemotherapy and radiotherapy in the treatment of these patients. We present the
      case of a xeroderma pigmentosum patient with a neck node recurrence of a squamous
      cell skin carcinoma that achieved a good response and survival with cetuximab.

PMID- 19106041
TI  - Knuckle pads, in an epidermal palmoplantar keratoderma patient with Keratin 9
      R163W transgrediens expression.
AB  - Epidermolytic PalmoPlantar keratoderma (EPPK) Vorner-type is an autosomal
      dominantly inherited skin disease, characterized by severe thickening of the
      palms and soles, caused by mutations in the keratin K9 (KRT9) gene. To date, a
      number of KRT9 mutations have been detected, most of which affect the highly
      conserved 1A region of the central alpha-helical domain, important for keratin
      heterodimerization. The most common mutation is the substitution of the arginine
      in position 163 with a tryptophan (R163W), which has been reported in North
      American, European, and Japanese populations. In a small number of cases, EPPK is
      associated with knuckle pad keratosis, but no correlation between this additional
      phenotype and a specific mutation has been found. Moreover, K9 is not normally
      expressed in knuckle skin, raising the question of the pathogenic mechanism
      leading to this additional phenotype. Here we show that in a family affected by
      EPPK and knuckle pad keratosis, carrying the R163W substitution, wild type (wt)
      and mutated K9 are strongly expressed in knuckle pads. These results suggest that
      the knuckle pad phenotype is due to ectopical expression of K9.

PMID- 19106043
TI  - Occupational cobalt induced systemic contact dermatitis.

PMID- 19106042
TI  - Differences between ulcerated and non-ulcerated hemangiomas, a retrospective
      study of 465 cases.
AB  - Our purpose was to get better insight into the ulceration of hemangiomas, by
      comparing patient characteristics of non-ulcerated hemangiomas with hemangiomas
      with active or past ulceration. A retrospective analysis was performed of files
      of patients who visited the Radboud University Medical Centre Nijmegen (UMCN),
      the Netherlands, between 1997 and 2007 for one or more infantile hemangiomas. The
      medical records of 465 patients were reviewed. Twenty three percent of the
      patients were diagnosed with ulceration. The size of ulcerated hemangiomas was
      significantly larger (28.6 cm2 vs. 6.0 cm2, p < 0.05). Predilection areas for
      ulceration were the head-neck region and the anogenital region. Ulceration was
      significantly most frequently seen in hemangiomas with a superficial (epidermal)
      component (98.5%, p < 0.05) and a segmental distribution (29.3%, p < 0.05).
      Ulceration most frequently took place during the proliferation phase of the
      hemangioma (83.1%). In the whole study population the male to female ratio was
      1:2 compared to a tendency to more girls (1:3) for the group with ulcerated
      hemangiomas (p = 0.08). We conclude that larger, more superficial hemangiomas in
      areas more susceptible to trauma and contamination were more likely to ulcerate.
      This study contributes to the possibility of assessing the likelihood of
      ulceration in an individual patient.

PMID- 19106044
TI  - Macrocephaly-cutis marmorata telangiectatica congenita.

PMID- 19106045
TI  - Pimecrolimus 1% cream is effective in the treatment of psoriasis in an infant.

PMID- 19106046
TI  - Cushing's syndrome caused by short-term topical glucocorticoid use for
      erythrodermic psoriasis and development of adrenal insufficiency after
      glucocorticoid withdrawal.

PMID- 19106047
TI  - Successful treatment of cutaneous leishmaniasis by photodynamic therapy and
      cryotherapy.

PMID- 19106048
TI  - Tinea barbae spreading to locus minoris resistentiae.

PMID- 19106049
TI  - Squamous cell carcinoma arising from hypertrophic lichen planus.

PMID- 19106050
TI  - Rosiglitazone inhibits RANTES expression by human epidermal keratinocytes.

PMID- 19106051
TI  - Lymphoepithelioma-like carcinoma of the skin mimicking a basal cell carcinoma.

PMID- 19106052
TI  - Dermatoses in Latin American immigrants seen in a tertiary hospital.
AB  - Europe, and in particular Spain, has become the destination of a considerable
      number of immigrants, 50% come from Latin America. The purpose of this study was
      to describe the cases of dermatoses seen in the immigrant Latin American
      population and compare them with those found in the control Spanish population.
      Over a year all the visits of economic immigrants seen in the Dermatology Section
      of the Hospital General Universitario de Alicante were prospectively recorded.
      During the study period 706 Latin American patients were seen. The most frequent
      dermatoses were eczema (18.2%), acne (6.5%) and non-genital viral warts (6.3%).
      The comparative study of dermatoses adjusted for age and sex, found a greater
      frequency of eczema, alopecia, melasma, herpes simplex, pilar keratosis, xerosis,
      and scabies (p < 0.01) in the Latin American population. On the other hand,
      melanocytic nevi and melanoma were less frequent in these patients (p < 0.05). We
      may say that the skin type and socio-sanitary conditions of the Latin American
      immigrant population lead to a greater frequency of eczema, melasma and scabies.
      In addition, the skin type and younger age favour a lower frequency of skin
      tumours.

PMID- 19106053
TI  - Symmetrical congenital dermoid fistulae of the anterior chest region.

PMID- 19106054
TI  - Reactive angioendotheliomatosis in a patient with Myelodysplastic Syndrome
      presenting as a cellulitis-like plaque.

PMID- 19106055
TI  - Coexisting gout, erythrodermic psoriasis and psoriatic arthritis.

PMID- 19106056
TI  - Cutaneous lupus erythematosus mimicking multiple keratoacanthomas.

PMID- 19106057
TI  - Proliferating pilomatricoma.

PMID- 19106058
TI  - Skin and mucosal fluorescence diagnosis with different light sources.
AB  - At the laboratory of Laser and Photodynamic Treatment (Institute of Oncology,
      Vilnius University) 98 patients with various kinds of skin and mucosal malignant,
      pre-malignant and benign lesions underwent 5-aminolevulinic acid (ALA) or its
      methyl ester (methyl aminolevulinate)-induced protoporphyrin IX (PpIX), or
      hematoporphyrin derivate (HpD) fluorescence imaging. Intensity and all other
      changes of fluorescence were evaluated and compared with the pathological
      findings. Margins of tumours were clearly outlined under fluorescent vision,
      giving a helpful contribution to diagnosis and therapy, even in clinically non
      visible tumours. Most of the malignant tumours were found to be fluorescent,
      whereas no fluorescence was observed in normal skin and mucosa. In the blue light
      mode, there is background blue fluorescence in normal tissue and red fluorescence
      in malignant areas. The suitability of different light wavelengths for
      fluorescence diagnosis (FD) was compared. From our data the most appropriate
      wavelength for this purpose is 401 nm.

PMID- 19106059
TI  - An alternate explanation for the decrease in pemphigus antibodies with
      combination treatment of double-filtration plasmapheresis and IVIg.

PMID- 19106060
TI  - Pancreatic panniculitis: an atypical clinical presentation.

PMID- 19106061
TI  - The Western Canada study: overview and context.

PMID- 19106062
TI  - Western Canada study of animal health effects associated with exposure to
      emissions from oil and natural gas field facilities. Study design and data
      collection I. Herd performance records and management.
AB  - Beef cow-calf herds are the most common livestock operation in Western Canada.
      Beef cows also have the greatest opportunity for direct contact with their
      environment through continuous sampling of the air, water, vegetation, and soil.
      These factors combine to make cow-calf herds a potentially useful sentinel of
      environmental change. Researchers individually tracked more than 33,000 cows in
      205 beef cow-calf herds from spring 2001 to the end of the calving season in 2002
      to examine the potential effects of emissions from the oil and gas industry on
      productivity. This article describes the study design and methodology of the
      Western Canada Study, with emphasis on herd-selection criteria and study
      implementation, the collection of herd-production data, and the challenges of
      tracking individual animals in a large prospective observational study-as the
      Western Canada Study is the largest on-farm study of its kind in North American
      cow-calf herds to date. The primary objective of this project was to examine the
      potential association between reproductive success and cumulative chronic
      exposure to sulfur dioxide, hydrogen sulfide, and volatile organic compounds in
      beef herds. Herd-selection criteria included potential exposure to oil and gas
      facilities, herd size, quality of available records, an established relationship
      with a local veterinary clinic, and participant interest. With the cooperation of
      local herd owners and veterinarians, on-farm collection of detailed individual
      animal data was successful in this group of cow-calf operations. Of the 212 herds
      initially selected to participate, complete calving season data for 2002 were
      available for 203 herds (96%). Individual animal records were available for more
      than 98% of eligible cows for each measurement period throughout the study. Herd
      production records were rated as satisfactory or better in 94% of the herds.
      These process outcomes confirm the practicality of using cow-calf herds as
      sentinel populations for environmental exposures and support the validity of
      subsequent research on these animal populations.

PMID- 19106063
TI  - Western Canada study of animal health effects associated with exposure to
      emissions from oil and natural gas field facilities. Study design and data
      collection II. Location of study herds relative to the oil and gas industry in
      Western Canada.
AB  - During the late part of 2000 and early months of 2001, project veterinarians
      recruited 205 beef herds to participate in a study of the effects of emissions
      from the upstream oil and gas industry on cattle reproduction and health.
      Researchers developed herd-selection criteria to optimize the range of exposure
      to facilities, including oil and gas wells, battery sites, and gas-gathering and
      gas-processing facilities across the major cattle-producing areas of Western
      Canada. Herds were initially selected on the basis of a ranking system of
      exposure potential on the basis of herd-owner reports of the locations of their
      operations in relation to oil and gas industry facilities. At the end of the
      study, researchers summarized data obtained from provincial regulatory agencies
      on facility location and reported flaring and venting volumes for each herd and
      compared these data to the original rankings of herd-exposure potential. Through
      this selection process, the researchers were successful in obtaining
      statistically significant differences in exposure to various types of oil and gas
      facility types and reported emissions among herds recruited for the study.

PMID- 19106064
TI  - Western Canada study of animal health effects associated with exposure to
      emissions from oil and natural gas field facilities. Study design and data
      collection III. Methods of assessing animal exposure to contaminants from the oil
      and gas industry.
AB  - Researchers measured exposure to oil and gas industry emissions in 205 cow-calf
      herds located in Western Canada. They measured airborne concentrations of sulfur
      dioxide, hydrogen sulfide, and volatile organic compounds with passive monitors
      placed in each pasture, wintering, or calving area that contained study animals
      from the start of the breeding season in the spring of 2001 until June 30, 2002.
      Researchers continued air monitoring in a subset of herds to the end of the study
      in fall 2002. Each sampling device was exposed for 1 month and then shipped to
      the laboratory for analysis. New samplers were installed and the shelters
      relocated, as necessary, to follow the movements of herd-management groups
      between pastures. Researchers linked the results of the air-monitoring analysis
      to individual animals for the relevant month. For the 205 herds examined at
      pregnancy testing in 2001, monthly mean exposures on the basis of all available
      data were as follows: sulfur dioxide, geometric mean (GM)=0.5 ppb, geometric
      standard deviation (GSD)=2.2; hydrogen sulfide, GM=0.14 ppb, GSD=2.3; benzene,
      GM=0.247 microg/m3, GSD=2.5; and toluene, GM=0.236 microg/m3, GSD=2.7. Benzene
      and toluene were surrogates for volatile organic compound exposure. In addition
      to passive measurements of air quality, researchers obtained data from provincial
      regulatory agencies on the density of oil and gas field facilities and on flaring
      and venting from the surrounding facilities. They developed the data into
      additional measures of exposure that were linked to each animal at each location
      for each month of the study.

PMID- 19106065
TI  - The association between exposure to the oil and gas industry and beef calf
      mortality in Western Canada.
AB  - Researchers assessed the association between exposure to emissions from oil and
      gas field facilities and newborn calf survival and health status by determining
      the risks of calf mortality and treatment reported for 27,511 beef calves born to
      cows in 203 herds, which were followed from the beginning of the 2001 breeding
      season through the 2002 calving season. They prospectively measured exposures to
      sulfur dioxide, hydrogen sulfide, and volatile organic compounds (VOCs) by using
      data from passive air monitors. They also used the density of oil and gas well
      sites surrounding each pasture as an additional measure of exposure. The
      researchers found that well-site density as well as exposures to hydrogen sulfide
      and VOCs measured as benzene or toluene were not associated with the odds of calf
      mortality in the first 3 months of life. After adjusting for cow-and herd-level
      risk factors, they found that exposure to sulfur dioxide near the time of calving
      was associated with an increased risk of calf mortality during this period.
      Exposure to sulfur dioxide in the 3-month period before calving was most
      suggestive of a causal exposure-response relationship (the odds ratio for every 1
      ppb increase in sulfur dioxide=1.32; 95% confidence interval=1.13-1.54; p=0004).
      Exposure to sulfur dioxide, hydrogen sulfide, and VOCs measured as benzene or
      toluene during gestation was not associated with the odds of calf treatment in
      the first 3 months of life. However, exposure to sulfur dioxide, hydrogen
      sulfide, and VOCs measured as benzene or toluene, and sulfur dioxide in the first
      month after calving, was associated with a small increase in the odds of calf
      treatment after the first month of life when risk was compared across quartiles
      for exposure; only the association between hydrogen sulfide exposure and the odds
      of treatment was consistent with a causal exposure.

PMID- 19106066
TI  - Risk of nonpregnancy, risk of disposal for pregnant cows, and duration of the
      calving interval in cow-calf herds exposed to the oil and gas industry in Western
      Canada.
AB  - To determine potential associations between emissions from oil and gas field
      facilities and the reproductive success of cow-calf herds in Western Canada,
      researchers followed approximately 33,000 beef cows from the beginning of the
      breeding season in 2001 through pregnancy testing in 2002. They prospectively
      measured exposure to sulfur dioxide, hydrogen sulfide, and volatile organic
      compounds (VOCs) by using data from passive air monitors installed in pastures
      and linked to the locations of individual animals. They used the density of oil
      and gas well sites surrounding each pasture as an additional measure of exposure.
      The researchers measured the risk of nonpregnancy in cattle in 205 herds in fall
      2001 and 200 herds in fall 2002, and they determined the interval between the
      dates of calving in 2001 and 2002 for all cows calving in both years from 202
      herds. The risk of disposal in pregnant cows was measured as the risk of removal
      from inventory for any reason other than nonpregnancy between pregnancy testing
      in 2001 and calving in 2002. There was no evidence that exposure to sulfur
      dioxide or VOCs measured as benzene and toluene increased the odds of
      nonpregnancy or disposal for pregnant cows. Density of oil and gas well sites was
      not related to the odds of nonpregnancy in either 2001 or 2002 or the odds of
      disposal for pregnant cows. During the first month after bull contact, exposures
      to increasing concentrations of sulfur dioxide, VOCs measured as toluene, and the
      density of oil and gas well sites were also not associated with an increase in
      the 2001-2002 breeding-to-calving interval. However, there was an estimated 3.0
      day increase in the breeding-to-calving interval for mature cows exposed to
      benzene concentrations in the highest quartile of exposure (>0.236 microg/m3)
      compared with those cows exposed to benzene concentrations in the lowest quartile
      of exposure (<0.082 microg/m3).

PMID- 19106068
TI  - A finite dissipative theory of temporary interfibrillar bridges in the
      extracellular matrix of ligaments and tendons.
AB  - The structural integrity and the biomechanical characteristics of ligaments and
      tendons result from the interactions between collagenous and non-collagenous
      proteins (e.g. proteoglycans, PGs) in the extracellular matrix. In this paper, a
      dissipative theory of temporary interfibrillar bridges in the anisotropic network
      of collagen type I, embedded in a ground substance, is derived. The
      glycosaminoglycan chains of decorin are assumed to mediate interactions between
      fibrils, behaving as viscous structures that transmit deformations outside the
      collagen molecules. This approach takes into account the dissipative effects of
      the unfolding preceding fibrillar elongation, together with the slippage of
      entire fibrils and the strain-rate-dependent damage evolution of the
      interfibrillar bridges. Thermodynamic consistency is used to derive the
      constitutive equations, and the transition state theory is applied to model the
      rearranging properties of the interfibrillar bridges. The constitutive theory is
      applied to reproduce the hysteretic spectrum of the tissues, demonstrating how
      PGs determine damage evolution, softening and non-recoverable strains in their
      cyclic mechanical response. The theoretical predictions are compared with the
      experimental response of ligaments and tendons from referenced studies. The
      relevance of the proposed model in mechanobiology research is discussed, together
      with several applications from medical practice to bioengineering science.

PMID- 19106069
TI  - Interconnected porous hydroxyapatite ceramics for bone tissue engineering.
AB  - Several porous calcium hydroxyapatite (HA) ceramics have been used clinically as
      bone substitutes, but most of them possessed few interpore connections, resulting
      in pathological fracture probably due to poor bone formation within the
      substitute. We recently developed a fully interconnected porous HA ceramic (IP
      CHA) by adopting the 'foam-gel' technique. The IP-CHA had a three-dimensional
      structure with spherical pores of uniform size (average 150 microm, porosity
      75%), which were interconnected by window-like holes (average diameter 40
      microm), and also demonstrated adequate compression strength (10-12 MPa). In
      animal experiments, the IP-CHA showed superior osteoconduction, with the majority
      of pores filled with newly formed bone. The interconnected porous structure
      facilitates bone tissue engineering by allowing the introduction of mesenchymal
      cells, osteotropic agents such as bone morphogenetic protein or vasculature into
      the pores. Clinically, we have applied the IP-CHA to treat various bony defects
      in orthopaedic surgery, and radiographic examinations demonstrated that grafted
      IP-CHA gained radiopacity more quickly than the synthetic HA in clinical use
      previously. We review the accumulated data on bone tissue engineering using the
      novel scaffold and on clinical application in the orthopaedic field.

PMID- 19106070
TI  - The role of innate immunity in atherogenesis.
AB  - Lipid peroxidation is a common event in health and is greatly accelerated in pro
      inflammatory settings such as hypercholesterolemia. Consequently, oxidation
      specific epitopes are generated, which are pro-inflammatory and immunogenic,
      leading to both adaptive and innate responses. Because innate immune mechanisms
      use conserved germline pattern recognition receptors (PRRs) that are preformed
      and present at birth, it is not obvious why they should bind to such epitopes. In
      this review, we put forward the hypothesis that because oxidation-specific
      epitopes are ubiquitous in both health and disease, and because they in essence
      represent "danger signals," they constitute a class of pathogen-associated
      molecular patterns leading to the natural selection of multiple innate PRRs that
      target such epitopes. We suggest that apoptotic cells, and the blebs and
      microparticles released from such cells, which are rich in oxidation-specific
      epitopes and thus pro-inflammatory, constitute an endogenous set of selecting
      antigens. In turn, natural antibodies, scavenger receptors, and soluble innate
      proteins, such as pentraxins, all represent PRRs that target such epitopes. We
      discuss the evidence for this hypothesis and the consequences of such responses
      in health and disease, such as atherosclerosis.

PMID- 19106071
TI  - Apolipoprotein E: structure determines function, from atherosclerosis to
      Alzheimer's disease to AIDS.
AB  - Apolipoprotein (apo) E has roles beyond lipoprotein metabolism. The detrimental
      effects of apoE4 in cardiovascular, neurological, and infectious diseases
      correlate with its structural features (e.g., domain interaction) that
      distinguish it from apoE3 and apoE2. Structure/function studies revealed that
      apoE2 is severely defective in LDL receptor binding because of a structural
      difference that alters the receptor binding region and helped unravel the
      mechanism of type III hyperlipoproteinemia. ApoE4 is the major genetic risk
      factor for Alzheimer's disease and sets the stage for neuropathological disorders
      precipitated by genetic, metabolic, and environmental stressors. ApoE also
      influences susceptibility to parasitic, bacterial, and viral infections. In HIV
      positive patients, apoE4 homozygosity hastens progression to AIDS and death and
      increases susceptibility to opportunistic infections. The next phase in our
      understanding of apoE will be characterized by clinical intervention to prevent
      or reverse the detrimental effects of apoE4 by modulating its structure or
      blocking the pathological processes it mediates.

PMID- 19106074
TI  - When chronic isn't chronic: the moderating role of active self-aspects.
AB  - The current work considered how self-concept organization moderates the
      consequences of chronic attributes, which are widely assumed to be always
      accessible and influential. In Study 1, the accessibility of participants'
      chronic attributes was assessed before and after activating a self-aspect that
      was either relevant or irrelevant to participants' chronic attributes. Results
      showed that chronic attributes were more accessible when they were relevant to a
      participant's active self-aspect than when they were irrelevant to it. In Study
      2, participants read ambiguous behaviors performed by others, some of which could
      be interpreted in line with their own chronic attribute or an alternative
      attribute. Participants were more likely to interpret behaviors as consistent
      with their own chronic attributes, but only when a relevant self-aspect had been
      previously activated. These studies suggest that chronicity can be moderated by
      self-aspect activation, consistent with the perspective that the self consists of
      multiple, context-dependent self-aspects.

PMID- 19106072
TI  - The thyromimetic T-0681 protects from atherosclerosis.
AB  - This report describes studies in hyperlipidemic New Zealand White (NZW) rabbits
      investigating the impact of the liver-selective thyromimetic T-0681 on
      lipoprotein metabolism and the development of atherosclerosis. Prolonged
      treatment with T-0681 increased the hepatic expression of both LDL receptor and
      scavenger receptor class B, type I without affecting cholesteryl ester transfer
      protein activity. Upregulation of hepatic lipoprotein receptors was accompanied
      by a marked decrease of apolipoprotein B-containing lipoproteins, reflected by a
      60% reduction of plasma cholesterol and a >70% reduction of plasma triglyceride
      levels. Most importantly, T-0681 reduced the development of atherosclerosis by
      80% in NZW rabbits on high-cholesterol chow. Our data suggest that liver
      selective thyromimetics, such as T-0681, may prove to be useful therapeutic
      agents against the development of atherosclerosis in humans.

PMID- 19106075
TI  - Race-based shifting standards and racial discrimination.
AB  - Members of stereotyped groups tend to be judged relative to group-specific
      standards such that subjective descriptions (smart, aggressive, tall) mean
      something different when they are applied to members of different groups. A
      "shifting standards" effect is present when judgments of group members on
      objective rating scales show stronger evidence of assimilation to stereotypes
      than the same judgments on subjective scales. This research asks whether the
      tendency to shift standards when judging the academic competence of Black and
      White students is related to measures of racial prejudice and to race-relevant
      decisions. In three studies, the tendency to shift standards was uncorrelated
      with other measures of prejudice but predicted reduced allocation of funds to a
      Black student organization, an effect moderated by implicit prejudice. The
      importance of examining interactions among indicators as they predict behavioral
      outcomes and implications for the conceptualization of prejudice are discussed.

PMID- 19106076
TI  - The dialectical self-concept: contradiction, change, and holism in East asian
      cultures.
AB  - Naive dialecticism refers to a set of East Asian lay beliefs characterized by
      tolerance for contradiction, the expectation of change, and cognitive holism. In
      five studies, the authors examined the cognitive mechanisms that give rise to
      global self-concept inconsistency among dialectical cultures. Contradictory self
      knowledge was more readily available (Study 1) and simultaneously accessible
      (Study 2) among East Asians (Japanese and Chinese) than among Euro-Americans.
      East Asians also exhibited greater change and holism in the spontaneous self
      concept (Study 1) and inconsistency in their implicit self-beliefs (Study 3).
      Cultural differences in self-concept inconsistency were obtained when controlling
      for alternative explanatory variables, including self-criticism (Study 4) and
      self-concept certainty (Studies 2 and 3) and were fully mediated by a direct
      measure of dialecticism (Study 5). Naive dialecticism provides a comprehensive
      theoretical framework for understanding these cultural differences and the
      contradictory, changeable, and holistic nature of the East Asian self-concept.

PMID- 19106077
TI  - Intergroup trust in Northern Ireland.
AB  - Although prominent political agendas have placed a great deal of importance on
      building trust in postconflict areas, there has been a lack of empirical research
      on its role in areas of intergroup conflict. The authors conducted two studies to
      examine the relationship between trust and intergroup behavioral tendencies-and
      the potential for intergroup contact to build trust in Northern Ireland. Study 1
      showed that outgroup trust mediates the impact of intergroup contact on
      behavioral tendencies toward the outgroup. Study 2 revealed the importance of
      trusting the outgroup over simply liking the outgroup; establishing outgroup
      trust is crucial, as trust is a stronger predictor of behavioral tendencies
      toward the outgroup than positive attitudes are. Results also demonstrated two
      mechanisms for increasing outgroup trust-through both direct and extended
      intergroup contact. These studies further our understanding of the psychological
      mechanisms underlying the formation of intergroup trust and behavior in areas of
      conflict.

PMID- 19106078
TI  - Finding the critical cue: implementation intentions to change one's diet work
      best when tailored to personally relevant reasons for unhealthy eating.
AB  - Implementation intentions promote acting on one's good intentions. But does
      specifying where and when to act also suffice when goals involve complex change
      that requires not merely initiating a behavior but rather substituting a habit
      with a new response? In a pilot study and two experiments, the authors
      investigated the efficacy of implementation intentions to replace unhealthy
      snacks with healthy snacks by linking different types of cues for unhealthy
      snacking (if-part) to healthy snacking (then-part). The pilot study identified
      cues for unhealthy snacking, differentiating between situational (where/when) and
      motivational (why) cues. Studies 1 and 2 tested the efficacy of implementation
      intentions that specified either situational or motivational cues in altering
      snacking habits. Results showed that implementation intentions specifying
      motivational cues decreased unhealthy snack consumption whereas the classic
      specification of where and when did not. Extending previous research, for complex
      behavior change "why" seems more important than "where and when."

PMID- 19106079
TI  - The strange case of sustained dedication to an unfulfilling relationship:
      predicting commitment and breakup from attachment anxiety and need fulfillment
      within relationships.
AB  - Two studies investigated whether need fulfillment within relationships moderates
      the associations of attachment anxiety with relationship commitment and
      persistence. The authors hypothesized that individuals who experience low
      attachment anxiety would exhibit declining commitment and increased risk of
      breakup if their partner failed to meet their core psychological needs, whereas
      individuals who experience high attachment anxiety would not. Study 1 employed
      longitudinal procedures to examine the associations among need fulfillment within
      relationships, attachment anxiety, commitment, and breakup. Study 2 employed
      experimental procedures to examine whether the temporary activation of attachment
      anxiety alters the association of need fulfillment with commitment. As predicted,
      relative to their high anxiety counterparts, individuals experiencing low
      attachment anxiety reported less commitment at study entry (Studies 1 and 2),
      declining commitment over time (Study 1), and an increased risk of breakup (Study
      1)-but only when their partner failed to help them fulfill their relatedness and
      autonomy needs.

PMID- 19106080
TI  - Why people stereotype affects how they stereotype: the differential influence of
      comprehension goals and self-enhancement goals on stereotyping.
AB  - In four studies, the authors examined the hypothesis that the way people
      stereotype is determined by the motives that instigate it. Study 1 measured and
      demonstrated the effectiveness of a commonly used priming technique to manipulate
      comprehension and self-enhancement goals. Study 2 demonstrated that why people
      stereotype determines how they stereotype: When a comprehension goal was salient,
      positive as well as negative stereotypes were applied, whereas a salient self
      enhancement goal led to the application of negative but not positive stereotypes.
      Study 3 replicated these effects with different stereotypes. Study 4 replicated
      these effects and gave more insight in the consequences of goal fulfillment on
      stereotyping. Results indicated the fulfillment of a salient self-enhancement or
      comprehension goal led to the reduction of stereotyping. These effects were goal
      specific: Fulfillment of a self-enhancement goal decreased enhancement-driven but
      not comprehension-driven stereotyping; fulfillment of a comprehension goal
      decreased comprehension-driven but not enhancement-driven stereotyping.

PMID- 19106081
TI  - The effects of minority/majority source status on attitude certainty: a matching
      perspective.
AB  - Building on recent work exploring metacognitive factors in minority/majority
      influence, three studies tested the hypothesis that when people receive
      persuasive messages from sources in the minority or majority, their attitude
      certainty can be determined by the extent to which source status and perceived
      argument quality match or mismatch. In Study 1, participants were presented with
      strong or weak arguments from a minority or majority source. Minority condition
      participants reported greater attitude certainty when arguments were weak rather
      than strong. Majority condition participants showed the opposite effect. Study 2
      replicated this interaction using a manipulation of perceived rather than actual
      argument quality. In Study 3, these effects only emerged when message recipients'
      processing motivation was high. Taken together, the results suggest that attitude
      certainty can be high or low following minority or majority messages, depending
      on processing motivation and message recipients' assessments of other persuasive
      evidence.

PMID- 19106082
TI  - A painful reminder: the role of level and salience of attitude importance in
      cognitive dissonance.
AB  - In his seminal book, L. Festinger (1957) emphasized the role of attitude
      importance in cognitive dissonance. This study (N = 308) explored whether
      people's use of dissonance reduction strategies differs as a function of level of
      attitude importance and whether the personal importance of an attitude is
      salient. Results showed that level and salience of attitude importance interacted
      to affect high-choice (HC) participants' tendency to use attitude change and
      trivialization to reduce dissonance. When HC participants were not reminded of
      the personal importance of their attitude (i.e., it was not salient), they
      changed their attitudes equally irrespective of attitude importance, but engaged
      in greater trivialization with increasing levels of importance. In contrast, when
      attitude importance was salient, HC participants changed their attitudes less
      with increasing attitude importance and showed no evidence of trivializing under
      any level of importance.

PMID- 19106083
TI  - Genetic determinants of response to clopidogrel and cardiovascular events.
AB  - BACKGROUND: Pharmacogenetic determinants of the response of patients to
      clopidogrel contribute to variability in the biologic antiplatelet activity of
      the drug. The effect of these determinants on clinical outcomes after an acute
      myocardial infarction is unknown. METHODS: We consecutively enrolled 2208
      patients presenting with an acute myocardial infarction in a nationwide French
      registry and receiving clopidogrel therapy. We then assessed the relation of
      allelic variants of genes modulating clopidogrel absorption (ABCB1), metabolic
      activation (CYP3A5 and CYP2C19), and biologic activity (P2RY12 and ITGB3) to the
      risk of death from any cause, nonfatal stroke, or myocardial infarction during 1
      year of follow-up. RESULTS: Death occurred in 225 patients, and nonfatal
      myocardial infarction or stroke in 94 patients, during the follow-up period. None
      of the selected single-nucleotide polymorphisms (SNPs) in CYP3A5, P2RY12, or
      ITGB3 were associated with a risk of an adverse outcome. Patients with two
      variant alleles of ABCB1 (TT at nucleotide 3435) had a higher rate of
      cardiovascular events at 1 year than those with the ABCB1 wild-type genotype (CC
      at nucleotide 3435) (15.5% vs. 10.7%; adjusted hazard ratio, 1.72; 95% confidence
      interval [CI], 1.20 to 2.47). Patients carrying any two CYP2C19 loss-of-function
      alleles (*2, *3, *4, or *5), had a higher event rate than patients with none
      (21.5% vs. 13.3%; adjusted hazard ratio, 1.98; 95% CI, 1.10 to 3.58). Among the
      1535 patients who underwent percutaneous coronary intervention during
      hospitalization, the rate of cardiovascular events among patients with two
      CYP2C19 loss-of-function alleles was 3.58 times the rate among those with none
      (95% CI, 1.71 to 7.51). CONCLUSIONS: Among patients with an acute myocardial
      infarction who were receiving clopidogrel, those carrying CYP2C19 loss-of
      function alleles had a higher rate of subsequent cardiovascular events than those
      who were not. This effect was particularly marked among the patients undergoing
      percutaneous coronary intervention. (ClinicalTrials.gov number, NCT00673036.)

PMID- 19106084
TI  - Cytochrome p-450 polymorphisms and response to clopidogrel.
AB  - BACKGROUND: Clopidogrel requires transformation into an active metabolite by
      cytochrome P-450 (CYP) enzymes for its antiplatelet effect. The genes encoding
      CYP enzymes are polymorphic, with common alleles conferring reduced function.
      METHODS: We tested the association between functional genetic variants in CYP
      genes, plasma concentrations of active drug metabolite, and platelet inhibition
      in response to clopidogrel in 162 healthy subjects. We then examined the
      association between these genetic variants and cardiovascular outcomes in a
      separate cohort of 1477 subjects with acute coronary syndromes who were treated
      with clopidogrel in the Trial to Assess Improvement in Therapeutic Outcomes by
      Optimizing Platelet Inhibition with Prasugrel-Thrombolysis in Myocardial
      Infarction (TRITON-TIMI) 38. RESULTS: In healthy subjects who were treated with
      clopidogrel, carriers of at least one CYP2C19 reduced-function allele
      (approximately 30% of the study population) had a relative reduction of 32.4% in
      plasma exposure to the active metabolite of clopidogrel, as compared with
      noncarriers (P<0.001). Carriers also had an absolute reduction in maximal
      platelet aggregation in response to clopidogrel that was 9 percentage points less
      than that seen in noncarriers (P<0.001). Among clopidogrel-treated subjects in
      TRITON-TIMI 38, carriers had a relative increase of 53% in the composite primary
      efficacy outcome of the risk of death from cardiovascular causes, myocardial
      infarction, or stroke, as compared with noncarriers (12.1% vs. 8.0%; hazard ratio
      for carriers, 1.53; 95% confidence interval [CI], 1.07 to 2.19; P=0.01) and an
      increase by a factor of 3 in the risk of stent thrombosis (2.6% vs. 0.8%; hazard
      ratio, 3.09; 95% CI, 1.19 to 8.00; P=0.02). CONCLUSIONS: Among persons treated
      with clopidogrel, carriers of a reduced-function CYP2C19 allele had significantly
      lower levels of the active metabolite of clopidogrel, diminished platelet
      inhibition, and a higher rate of major adverse cardiovascular events, including
      stent thrombosis, than did noncarriers.

PMID- 19106085
TI  - A novel proteomics approach for the discovery of chromatin-associated protein
      networks.
AB  - Protein-protein interaction mapping has progressed rapidly in recent years,
      enabling the completion of several high throughput studies. However, knowledge of
      physical interactions is limited for numerous classes of proteins, such as
      chromatin-bound proteins, because of their poor solubility when bound to DNA. To
      address this problem, we have developed a novel method, termed modified chromatin
      immunopurification (mChIP), that allows for the efficient purification of protein
      DNA macromolecules, enabling subsequent protein identification by mass
      spectrometry. mChIP consists of a single affinity purification step whereby
      chromatin-bound protein networks are isolated from mildly sonicated and gently
      clarified cellular extracts using magnetic beads coated with antibodies. We
      applied the mChIP method in Saccharomyces cerevisiae cells expressing
      endogenously tandem affinity purification (TAP)-tagged histone H2A or the histone
      variant Htz1p and successfully co-purified numerous chromatin-bound protein
      networks as well as DNA. We further challenged the mChIP procedure by purifying
      three chromatin-bound bait proteins that have proven difficult to purify by
      traditional methods: Lge1p, Mcm5p, and Yta7p. The protein interaction networks of
      these three baits dramatically expanded our knowledge of their chromatin
      environments and illustrate that the innovative mChIP procedure enables an
      improved characterization of chromatin-associated proteins.

PMID- 19106086
TI  - A simulated MS/MS library for spectrum-to-spectrum searching in large scale
      identification of proteins.
AB  - Identifying peptides from mass spectrometric fragmentation data (MS/MS spectra)
      using search strategies that map protein sequences to spectra is computationally
      expensive. An alternative strategy uses direct spectrum-to-spectrum matching
      against a reference library of previously observed MS/MS that has the advantage
      of evaluating matches using fragment ion intensities and other ion types than the
      simple set normally used. However, this approach is limited by the small sizes of
      the available peptide MS/MS libraries and the inability to evaluate the rate of
      false assignments. In this study, we observed good performance of simulated
      spectra generated by the kinetic model implemented in MassAnalyzer (Zhang, Z.
      (2004) Prediction of low-energy collision-induced dissociation spectra of
      peptides. Anal. Chem. 76, 3908-3922; Zhang, Z. (2005) Prediction of low-energy
      collision-induced dissociation spectra of peptides with three or more charges.
      Anal. Chem. 77, 6364-6373) as a substitute for the reference libraries used by
      the spectrum-to-spectrum search programs X!Hunter and BiblioSpec and similar
      results in comparison with the spectrum-to-sequence program Mascot. We also
      demonstrate the use of simulated spectra for searching against decoy sequences to
      estimate false discovery rates. Although we found lower score discrimination with
      spectrum-to-spectrum searches than with Mascot, particularly for higher charge
      forms, comparable peptide assignments with low false discovery rate were achieved
      by examining consensus between X!Hunter and Mascot, filtering results by mass
      accuracy, and ignoring score thresholds. Protein identification results are
      comparable to those achieved when evaluating consensus between Sequest and
      Mascot. Run times with large scale data sets using X!Hunter with the simulated
      spectral library are 7 times faster than Mascot and 80 times faster than Sequest
      with the human International Protein Index (IPI) database. We conclude that
      simulated spectral libraries greatly expand the search space available for
      spectrum-to-spectrum searching while enabling principled analyses and that the
      approach can be used in consensus strategies for large scale studies while
      reducing search times.

PMID- 19106087
TI  - Functional differentiation of Brassica napus guard cells and mesophyll cells
      revealed by comparative proteomics.
AB  - Guard cells are highly specialized cells that form tiny pores called stomata on
      the leaf surface. The opening and closing of stomata control leaf gas exchange
      and water transpiration as well as allow plants to quickly respond and adjust to
      new environmental conditions. Mesophyll cells are specialized for photosynthesis.
      Despite the phenotypic and obvious functional differences between the two types
      of cells, the full protein components and their functions have not been explored
      but are addressed here through a global comparative proteomics analysis of
      purified guard cells and mesophyll cells. With the use of isobaric tags for
      relative and absolute quantification (iTRAQ) tagging and two-dimensional liquid
      chromatography mass spectrometry, we identified 1458 non-redundant proteins in
      both guard cells and mesophyll cells of Brassica napus leaves. Based on stringent
      statistical criteria, a total of 427 proteins were quantified, and 74 proteins
      were found to be enriched in guard cells. Proteins involved in energy
      (respiration), transport, transcription (nucleosome), cell structure, and
      signaling are preferentially expressed in guard cells. We observed several well
      characterized guard cell proteins. By contrast, proteins involved in
      photosynthesis, starch synthesis, disease/defense/stress, and other metabolisms
      are preferentially represented in mesophyll cells. Of the identified proteins,
      110 have corresponding microarray data obtained from Arabidopsis guard cells and
      mesophyll cells. About 72% of these proteins follow the same trend of expression
      at the transcript and protein levels. For the rest of proteins, the correlation
      between proteomics data and the microarray data is poor. This highlights the
      importance of quantitative profiling at the protein level. Collectively this work
      represents the most extensive proteomic description of B. napus guard cells and
      has improved our knowledge of the functional specification of guard cells and
      mesophyll cells.

PMID- 19106088
TI  - Spatial distribution of protein kinase A activity during cell migration is
      mediated by A-kinase anchoring protein AKAP Lbc.
AB  - Protein kinase A (PKA) has been suggested to be spatially regulated in migrating
      cells due to its ability to control signaling events that are critical for
      polarized actin cytoskeletal dynamics. Here, using the fluorescence resonance
      energy transfer-based A-kinase activity reporter (AKAR1), we find that PKA
      activity gradients form with the strongest activity at the leading edge and are
      restricted to the basal surface in migrating cells. The existence of these
      gradients was confirmed using immunocytochemistry using phospho-PKA substrate
      antibodies. This observation holds true for carcinoma cells migrating randomly on
      laminin-1 or stimulated to migrate on collagen I with lysophosphatidic acid.
      Phosphodiesterase inhibition allows the formation of PKA activity gradients;
      however, these gradients are no longer polarized. PKA activity gradients are not
      detected when a non-phosphorylatable mutant of AKAR1 is used, if PKA activity is
      inhibited with H-89 or protein kinase inhibitor, or when PKA anchoring is
      perturbed. We further find that a specific A-kinase anchoring protein, AKAP-Lbc,
      is a major contributor to the formation of these gradients. In summary, our data
      show that PKA activity gradients are generated at the leading edge of migrating
      cells and provide additional insight into the mechanisms of PKA regulation of
      cell motility.

PMID- 19106090
TI  - A major peroxiredoxin-induced activation of Yap1 transcription factor is mediated
      by reduction-sensitive disulfide bonds and reveals a low level of transcriptional
      activation.
AB  - Redox reactions involving cysteine thiol-disulfide exchange are crucial for the
      intracellular monitoring of hydrogen peroxide (H(2)O(2)). Yap1, the master
      transcription factor for the oxidative stress response in budding yeast, is
      activated by the formation of disulfide bonds in response to H(2)O(2). Gpx3
      (glutathione peroxidase-like protein 3) acts as a receptor for H(2)O(2), and Ybp1
      (Yap1-binding protein 1) is crucial for Gpx3-dependent disulfide bond formation
      in Yap1. We previously reported that Tsa1, a major peroxiredoxin in yeast cells,
      is required for activation of Yap1 in a widely used yeast strain, W303-1b,
      carrying the ybp1-1 mutant allele encoding a truncated Ybp1 protein. In the
      present study, we show that Tsa1 can interact with Yap1 via disulfide linkages
      and induce the formation of intramolecular disulfide bonds in Yap1 in ybp1-1
      cells. The results provide evidence that Prx can have intrinsic activity as an
      H(2)O(2) receptor and can relay H(2)O(2) as a signal to the Prx target proteins
      in terms of formation of disulfide linkage. Furthermore, our data reveal that
      there is more of the reduction-resistant active form of Yap1 (i.e. Yap1 (oxII))
      when it is partnered with Gpx3 than with Tsa1. These data support our hypothesis
      that changes in the redox status of Yap1 to reduction-resistant forms by multiple
      disulfide bond formation are important for determining the level and duration of
      Yap1 activity in the dynamic equilibrium of redox reactions in cells exposed to
      H(2)O(2).

PMID- 19106091
TI  - In situ mitochondrial Ca2+ buffering differences of intact neurons and astrocytes
      from cortex and striatum.
AB  - The striatum is particularly vulnerable to neurological disorders, such as
      Huntington disease. Previous studies, with nonsynaptic mitochondria isolated from
      cortical and striatal homogenates, suggest that striatal mitochondria are highly
      vulnerable to Ca(2+) loads, possibly influencing striatal vulnerability. However,
      whether and how neuronal and glial mitochondria from cortex and striatum differ
      in Ca(2+) vulnerability remains unknown. We test this hypothesis using a novel
      strategy allowing comparisons of mitochondrial Ca(2+) buffering capacity in
      cortical and striatal neuron-astrocyte co-cultures. We provide original evidence
      that mitochondria not only in neurons but also in astrocytes from striatal origin
      exhibit a decreased Ca(2+) buffering capacity when compared with cortical
      counterparts. The decreased mitochondrial Ca(2+) buffering capacity in striatal
      versus cortical astrocytes does not stem from variation in mitochondrial
      concentration or in the rate of intracellular Ca(2+) elevation, being
      mechanistically linked to an increased propensity to undergo cyclosporin A (CsA)
      sensitive permeability transition. Indeed, 1 microm CsA selectively increased the
      mitochondrial Ca(2+) buffering capacity of striatal astrocytes, without modifying
      that of neurons or cortical astrocytes. Neither thapsigargin nor FK506 modified
      mitochondrial Ca(2+) buffering differences between cell types, excluding a
      predominant contribution of endoplasmic reticulum or calcineurin. These results
      provide additional insight into the mechanisms of striatal vulnerability, showing
      that the increased Ca(2+) vulnerability of striatal versus cortical mitochondria
      resides in both intact neurons and astrocytes, thus positioning the striatum at
      greater risk for disturbed neuron-astrocyte interactions. Also, the selective
      effect of CsA over striatal astrocytes suggests that in vivo neuronal sheltering
      with this compound may indirectly result from astrocytic protection.

PMID- 19106089
TI  - The death effector domain-containing DEDD supports S6K1 activity via preventing
      Cdk1-dependent inhibitory phosphorylation.
AB  - Cell cycle regulation and biochemical responses upon nutrients and growth factors
      are the major regulatory mechanisms for cell sizing in mammals. Recently, we
      identified that the death effector domain-containing DEDD impedes mitotic
      progression by inhibiting Cdk1 (cyclin-dependent kinase 1) and thus maintains an
      increase of cell size during the mitotic phase. Here we found that DEDD also
      associates with S6 kinase 1 (S6K1), downstream of phosphatidylinositol 3-kinase,
      and supports its activity by preventing inhibitory phosphorylation of S6K1
      brought about by Cdk1 during the mitotic phase. DEDD(-/-) cells showed reduced
      S6K1 activity, consistently demonstrating decreased levels in activating
      phosphorylation at the Thr-389 site. In addition, levels of Cdk1-dependent
      inhibitory phosphorylation at the C terminus of S6K1 were enhanced in DEDD(-/-)
      cells and tissues. Consequently, as in S6K1(-/-) mice, the insulin mass within
      pancreatic islets was reduced in DEDD(-/-) mice, resulting in glucose
      intolerance. These findings suggest a novel cell sizing mechanism achieved by
      DEDD through the maintenance of S6K1 activity prior to cell division. Our results
      also suggest that DEDD may harbor important roles in glucose homeostasis and that
      its deficiency might be involved in the pathogenesis of type 2 diabetes mellitus.

PMID- 19106092
TI  - Superoxide dismutase 1-mediated production of ethanol- and DNA-derived radicals
      in yeasts challenged with hydrogen peroxide: molecular insights into the genome
      instability of peroxiredoxin-null strains.
AB  - Peroxiredoxins are receiving increasing attention as defenders against oxidative
      damage and sensors of hydrogen peroxide-mediated signaling events. In the yeast
      Saccharomyces cerevisiae, deletion of one or more isoforms of the peroxiredoxins
      is not lethal but compromises genome stability by mechanisms that remain under
      scrutiny. Here, we show that cytosolic peroxiredoxin-null cells
      (tsa1Deltatsa2Delta) are more resistant to hydrogen peroxide than wild-type (WT)
      cells and consume it faster under fermentative conditions. Also,
      tsa1Deltatsa2Delta cells produced higher yields of the 1-hydroxyethyl radical
      from oxidation of the glucose metabolite ethanol, as proved by spin-trapping
      experiments. A major role for Fenton chemistry in radical formation was excluded
      by comparing WT and tsa1Deltatsa2Delta cells with respect to their levels of
      total and chelatable metal ions and of radical produced in the presence of
      chelators. The main route for 1-hydroxyethyl radical formation was ascribed to
      the peroxidase activity of Cu,Zn-superoxide dismutase (Sod1), whose expression
      and activity increased approximately 5- and 2-fold, respectively, in
      tsa1Deltatsa2Delta compared with WT cells. Accordingly, overexpression of human
      Sod1 in WT yeasts led to increased 1-hydroxyethyl radical production. Relevantly,
      tsa1Deltatsa2Delta cells challenged with hydrogen peroxide contained higher
      levels of DNA-derived radicals and adducts as monitored by immuno-spin trapping
      and incorporation of (14)C from glucose into DNA, respectively. The results
      indicate that part of hydrogen peroxide consumption by tsa1Deltatsa2Delta cells
      is mediated by induced Sod1, which oxidizes ethanol to the 1-hydroxyethyl
      radical, which, in turn, leads to increased DNA damage. Overall, our studies
      provide a pathway to account for the hypermutability of peroxiredoxin-null
      strains.

PMID- 19106093
TI  - Role of Cys-1327 and Cys-1337 in redox sensitivity and allosteric monitoring in
      human carbamoyl phosphate synthetase.
AB  - Human carbamoyl phosphate synthetase (hCPS) has evolved critical features that
      allow it to remove excess and potentially neurotoxic ammonia via the urea cycle,
      including use of only free ammonia as a nitrogen donor, a K(m) for ammonia 100
      fold lower than for CPSs that also use glutamine as a nitrogen donor, and
      required allosteric activation by N-acetylglutamate (AGA), a sensor of excess
      amino acids. The recent availability of a Schizosaccharomyces pombe expression
      system for hCPS allowed us to utilize protein engineering approaches to elucidate
      the distinctive hCPS properties. Although the site of AGA interaction is not
      defined, it is known that the binding of AGA to CPS leads to a conformational
      change in which a pair of cysteine side chains become proximate and can then be
      selectively induced to undergo disulfide bonding. We analyzed the response of
      hCPS cysteine mutants to thiol-specific reagents and identified Cys-1327 and Cys
      1337 as the AGA-responsive proximate cysteines. Possibly two of the features
      unique to urea-specific CPSs, relative to other CPSs (the conserved Cys-1327/Cys
      1337 pair and the occurrence at very high concentrations in the liver
      mitochondrial matrix) co-evolved to provide buffering against reactive oxygen
      species. Reciprocal mutation analysis of Escherichia coli CPS (eCPS), creating
      P909C and G919C and establishing the ability of these engineered cysteine
      residues to share a disulfide bond, indicated an eCPS conformational change at
      least partly similar to the hCPS conformational change induced by AGA. These
      findings strongly suggested an alternative eCPS conformation relative to the
      single crystal conformation thus far identified.

PMID- 19106094
TI  - Deubiquitination of CXCR4 by USP14 is critical for both CXCL12-induced CXCR4
      degradation and chemotaxis but not ERK ativation.
AB  - The chemokine receptor CXCR4 plays important roles in the immune and nervous
      systems. Abnormal expression of CXCR4 contributes to cancer and inflammatory and
      neurodegenerative disorders. Although ligand-dependent CXCR4 ubiquitination is
      known to accelerate CXCR4 degradation, little is known about counter mechanisms
      for receptor deubiquitination. CXCL12, a CXCR4 agonist, induces a time-dependent
      association of USP14 with CXCR4, or its C terminus, that is not mimicked by
      USP2A, USP4, or USP7, other members of the deubiquitination catalytic family. Co
      localization of CXCR4 and USP14 also is time-dependent following CXCL12
      stimulation. The physical interaction of CXCR4 and USP14 is paralleled by USP14
      catalyzed deubiquitination of the receptor; knockdown of endogenous USP14 by RNA
      interference (RNAi) blocks CXCR4 deubiquitination, whereas overexpression of
      USP14 promotes CXCR4 deubiquitination. We also observed that ubiquitination of
      CXCR4 facilitated receptor degradation, whereas overexpression of USP14 or RNAi
      induced knockdown of USP14 blocked CXCL12-mediated CXCR4 degradation. Most
      interestingly, CXCR4-mediated chemotactic cell migration was blocked by either
      overexpression or RNAi-mediated knockdown of USP14, implying that a CXCR4
      ubiquitin cycle on the receptor, rather than a particular ubiquitinated state of
      the receptor, is critical for the ligand gradient sensing and directed motility
      required for chemokine-mediated chemotaxis. Our observation that a mutant of
      CXCR4, HA-3K/R CXCR4, which cannot be ubiquitinated and does not mediate a
      chemotactic response to CXCL12, indicates the importance of this covalent
      modification not only in marking receptors for degradation but also for
      permitting CXCR4-mediated signaling. Finally, the indistinguishable activation of
      ERK by wild typeor 3K/R-CXCR4 suggests that chemotaxis in response to CXCL12 may
      be independent of the ERK cascade.

PMID- 19106095
TI  - Negative and positive regulation of MAPK phosphatase 3 controls platelet-derived
      growth factor-induced Erk activation.
AB  - MAPK phosphatases (MKPs) are dual specificity phosphatases that dephosphorylate
      and thereby inactivate MAPKs. In the present study, we provide evidence that
      platelet-derived growth factor BB (PDGF-BB) regulates MKP3 (DUSP6), which is
      considered to be a phosphatase highly selective for Erk. Intriguingly, we
      observed that Mek is positively regulated by MKP3, whereas Erk itself is
      negatively regulated. In addition, we found that activation of PDGF receptor
      alpha or beta leads to a rapid proteasomal degradation of MKP3 in a manner that
      requires Mek activation; this feed-forward mechanism was found to be essential
      for efficient Erk phosphorylation. We could also demonstrate that PDGF-BB
      stimulation induces phosphorylation of MKP3 at Ser-174 and Ser-300;
      phosphorylation of Ser-174 is involved in PDGF-induced MKP3 degradation, since
      mutation of this site stabilized MKP3. Moreover, activated Erk induces mkp3
      expression, leading to restoration of MKP3 levels after 1-2 h and a concomitant
      dephosphorylation of Erk in cells with activated PDGFRalpha. Reducing the MKP3
      level by small interfering RNA leads to an increased Erk activation and mitogenic
      response to PDGF-BB. In conclusion, MKP3 is an important regulator of PDGF
      induced Erk phosphorylation acting in both a rapid positive feed-forward and a
      later negative feed-back loop.

PMID- 19106096
TI  - PEP-19, an intrinsically disordered regulator of calmodulin signaling.
AB  - PEP-19 is a small calmodulin (CaM)-binding protein that greatly increases the
      rates of association and dissociation of Ca(2+) from the C-domain of CaM, an
      effect that is mediated by an acidic/IQ sequence in PEP-19. We show here using
      NMR that PEP-19 is an intrinsically disordered protein, but with residual
      structure localized to its acidic/IQ motif. We also show that the k(on) and
      k(off) rates for binding PEP-19 to apo-CaM are at least 50-fold slower than for
      binding to Ca(2+)-CaM. These data indicate that intrinsic disorder confers
      plasticity that allows PEP-19 to bind to either apo- or Ca(2+)-CaM via different
      structural modes, and that complex formation may be facilitated by conformational
      selection of residual structure in the acidic/IQ sequence.

PMID- 19106097
TI  - Rab2 utilizes glyceraldehyde-3-phosphate dehydrogenase and protein kinase C{iota}
      to associate with microtubules and to recruit dynein.
AB  - Rab2 requires glyceraldehyde-3-phosphate dehydrogenase (GAPDH) and atypical
      protein kinase Ciota (aPKCiota) for retrograde vesicle formation from vesicular
      tubular clusters that sort secretory cargo from recycling proteins returned to
      the endoplasmic reticulum. However, the precise role of GAPDH and aPKCiota in the
      early secretory pathway is unclear. GAPDH was the first glycolytic enzyme
      reported to co-purify with microtubules (MTs). Similarly, aPKC associates
      directly with MTs. To learn whether Rab2 also binds directly to MTs, a MT binding
      assay was performed. Purified Rab2 was found in a MT-enriched pellet only when
      both GAPDH and aPKCiota were present, and Rab2-MT binding could be prevented by a
      recombinant fragment made to the Rab2 amino terminus (residues 2-70), which
      directly interacts with GAPDH and aPKCiota. Because GAPDH binds to the carboxyl
      terminus of alpha-tubulin, we characterized the distribution of
      tyrosinated/detyrosinated alpha-tubulin that is recruited by Rab2 in a
      quantitative membrane binding assay. Rab2-treated membranes contained
      predominantly tyrosinated alpha-tubulin; however, aPKCiota was the limiting and
      essential factor. Tyrosination/detyrosination influences MT motor protein
      binding; therefore, we determined whether Rab2 stimulated kinesin or dynein
      membrane binding. Although kinesin was not detected on membranes incubated with
      Rab2, dynein was recruited in a dose-dependent manner, and binding was aPKCiota
      dependent. These combined results suggest a mechanism by which Rab2 controls MT
      and motor recruitment to vesicular tubular clusters.

PMID- 19106098
TI  - Ablation of ventricular myosin regulatory light chain phosphorylation in mice
      causes cardiac dysfunction in situ and affects neighboring myofilament protein
      phosphorylation.
AB  - There is little direct evidence on the role of myosin regulatory light chain
      phosphorylation in ejecting hearts. In studies reported here we determined the
      effects of regulatory light chain (RLC) phosphorylation on in situ cardiac
      systolic mechanics and in vitro myofibrillar mechanics. We compared data obtained
      from control nontransgenic mice (NTG) with a transgenic mouse model expressing a
      cardiac specific nonphosphorylatable RLC (TG-RLC(P-). We also determined whether
      the depression in RLC phosphorylation affected phosphorylation of other
      sarcomeric proteins. TG-RLC(P-) demonstrated decreases in base-line load
      independent measures of contractility and power and an increase in ejection
      duration together with a depression in phosphorylation of myosin-binding protein
      C (MyBP-C) and troponin I (TnI). Although TG-RLC(P-) displayed a significantly
      reduced response to beta(1)-adrenergic stimulation, MyBP-C and TnI were
      phosphorylated to a similar level in TG-RLC(P-) and NTG, suggesting cAMP
      dependent protein kinase signaling to these proteins was not disrupted. A major
      finding was that NTG controls were significantly phosphorylated at RLC serine 15
      following beta(1)-adrenergic stimulation, a mechanism prevented in TG-RLC(P-),
      thus providing a biochemical difference in beta(1)-adrenergic responsiveness at
      the level of the sarcomere. Our measurements of Ca(2+) tension and Ca(2+)-ATPase
      rate relations in detergent-extracted fiber bundles from LV trabeculae
      demonstrated a relative decrease in maximum Ca(2+)-activated tension and tension
      cost in TG-RLC(P-) fibers, with no change in Ca(2+) sensitivity. Our data
      indicate that RLC phosphorylation is critical for normal ejection and response to
      beta(1)-adrenergic stimulation. Our data also indicate that the lack of RLC
      phosphorylation promotes compensatory changes in MyBP-C and TnI phosphorylation,
      which when normalized do not restore function.

PMID- 19106100
TI  - MCAF1/AM is involved in Sp1-mediated maintenance of cancer-associated telomerase
      activity.
AB  - Telomerase maintains telomere length and is implicated in senescence and
      immortalization of mammalian cells. Two essential components for this enzyme are
      telomerase reverse transcriptase (TERT) and the telomerase RNA component (encoded
      by the TERC gene). These telomerase subunit genes are known to be mainly
      expressed by specificity protein 1 (Sp1). MBD1-containing chromatin-associated
      factor 1 (MCAF1), also known as ATFa-associated modulator (AM) and activating
      transcription factor 7-interacting protein (ATF7IP), mediates gene regulation,
      although the precise function of MCAF1 remains to be elucidated. Here, we report
      that MCAF1 is involved in Sp1-dependent maintenance of telomerase activity in
      cancer cells. Two evolutionarily conserved domains of MCAF1 directly interact
      with Sp1 and the general transcriptional apparatus. Selective depletion of MCAF1
      or Sp1 down-regulates TERT and TERC genes in cultured cells, which results in
      decreased telomerase activity. The transcriptionally active form of RNA
      polymerase II and the general transcription factor ERCC3 decreased in the TERT
      promoter under the loss of MCAF1 or Sp1. Consistently, MCAF1 is found to be
      frequently overexpressed in naturally occurring cancers that originate in
      different tissues. Our data suggest that transcriptional function of MCAF1
      facilitates telomerase expression by Sp1, which may be a common mechanism in
      proliferative cancer cells.

PMID- 19106099
TI  - Context-dependent function of regulatory elements and a switch in chromatin
      occupancy between GATA3 and GATA2 regulate Gata2 transcription during trophoblast
      differentiation.
AB  - GATA transcription factors are important regulators of tissue-specific gene
      expression during development. GATA2 and GATA3 have been implicated in the
      regulation of trophoblast-specific genes. However, the regulatory mechanisms of
      GATA2 expression in trophoblast cells are poorly understood. In this study, we
      demonstrate that Gata2 is transcriptionally induced during trophoblast giant cell
      specific differentiation. Transcriptional induction is associated with
      displacement of GATA3-dependent nucleoprotein complexes by GATA2-dependent
      nucleoprotein complexes at two regulatory regions, the -3.9- and +9.5-kb regions,
      of the mouse Gata2 locus. Analyses with reporter genes showed that, in
      trophoblast cells, -3.9- and +9.5-kb regions function as transcriptional
      enhancers in GATA motif independent and dependent fashions, respectively. We also
      found that knockdown of GATA3 by RNA interference induces GATA2 in
      undifferentiated trophoblast cells. Interestingly, three other known GATA motif
      dependent Gata2 regulatory elements, the -1.8-, -2.8-, and -77-kb regions, which
      are important to regulate Gata2 in hematopoietic cells are not occupied by GATA
      factors in trophoblast cells. These elements do not show any enhancer activity
      and also possess inaccessible chromatin structure in trophoblast cells indicating
      a context-dependent function. Our results indicate that GATA3 directly represses
      Gata2 in undifferentiated trophoblast cells, and a switch in chromatin occupancy
      between GATA3 and GATA2 (GATA3/GATA2 switch) induces transcription during
      trophoblast differentiation. We predict that this GATA3/GATA2 switch is an
      important mechanism for the transcriptional regulation of other trophoblast
      specific genes.

PMID- 19106101
TI  - Target of rapamycin (TOR) mediates the transduction of nutritional signals into
      juvenile hormone production.
AB  - Anautogeny is a reproductive strategy by which females do not reproduce until
      they feed. Therefore, nutritional signals must inform the reproductive tissues,
      and cells that the organism has reached a nutritional status suitable for
      triggering reproductive processes. One of the possible pathways involved in
      anautogeny is the "target of rapamycin" (TOR) pathway, which has been described
      as connecting the nutritional status with growth, proliferation, and cancer. The
      German cockroach, Blattella germanica, is an anautogenous species whose
      vitellogenesis is governed by juvenile hormone. In the present report, we
      describe the cloning of TOR cDNA from B. germanica (BgTOR). Expression studies
      showed that BgTOR is expressed in adult female corpora allata and fat body. BgTOR
      knockdown using systemic RNAi in vivo produced a severe inhibition of juvenile
      hormone synthesis in adult female corpora allata, together with a reduction of
      mRNA levels corresponding to 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA)
      synthase-1, HMG-CoA synthase-2, and HMG-CoA reductase. In addition, there was a
      reduction of vitellogenin mRNA in the fat body, and ovaries did not grow.
      Analysis of TOR expression in corpora allata of fed and starved females suggested
      that TOR is not regulated at the transcriptional level. Nevertheless, there was a
      reduction in HMG-CoA synthases and reductase mRNA in corpora allata (but not in
      the fat body) of starved females, together with a dramatic reduction of juvenile
      hormone production and ovary development. Taken together, our results indicate
      that TOR knockdown mimics starvation in terms of corpora allata activity, and
      suggest that nutritional signals that activate juvenile hormone biosynthesis and
      vitellogenin production are mediated by the TOR pathway.

PMID- 19106102
TI  - Anionic amino acids near the pro-alpha-defensin N terminus mediate inhibition of
      bactericidal activity in mouse pro-cryptdin-4.
AB  - In mouse Paneth cells, alpha-defensins, termed cryptdins (Crps), are activated by
      matrix metalloproteinase-7-mediated proteolysis of inactive precursors (pro-Crps)
      to bactericidal forms. The activating cleavage step at Ser(43) downward arrow
      Ile(44) in mouse pro-Crp4-(20-92) removes nine acidic amino acids that
      collectively block the membrane-disruptive behavior of the Crp4 moiety of the
      proform. This inhibitory mechanism has been investigated further to identify
      whether specific cluster(s) of electronegative amino acids in pro-Crp4-(20-43)
      are responsible for blocking bactericidal activity and membrane disruption. To
      test whether specific cluster(s) of electronegative amino acids in pro-Crp4-(20
      43) have specific positional effects that block bactericidal peptide activity and
      membrane disruption, acidic residues positioned at the distal (Asp(20), Asp(26),
      Glu(27), and Glu(28)), mid (Glu(32) and Glu(33)), and proximal (Glu(37), Glu(38),
      and Asp(39)) clusters in pro-Crp4-(20-92) were mutagenized, and variants were
      assayed for differential effects of mutagenesis on bactericidal peptide activity.
      Substitution of the mid and proximal Asp and Glu clusters with Gly produced
      additive effects with respect to the induction of both bactericidal activity and
      membrane permeabilization of live Escherichia coli ML35 cells. In contrast,
      substitution of distal Glu and Asp residues with Gly or their deletion resulted
      in pro-Crp4-(20-92) variants with bactericidal and membrane-disruptive activities
      equal to or greater than that of fully mature Crp4. These findings support the
      conclusion that the most distal N-terminal anionic residues of pro-Crp4-(20-92)
      are primarily responsible for blocking Crp4-mediated membrane disruption in the
      precursor.

PMID- 19106103
TI  - Angiopoietin-1 induces Kruppel-like factor 2 expression through a
      phosphoinositide 3-kinase/AKT-dependent activation of myocyte enhancer factor 2.
AB  - Angiopoietin-1 (Ang1) regulates both vascular quiescence and angiogenesis through
      the receptor tyrosine kinase Tie2. We and another group have recently shown that
      Ang1 and Tie2 form distinct signaling complexes at cell-cell and cell-matrix
      contacts and further demonstrated that the former selectively induces expression
      of Kruppel-like factor 2 (KLF2), a transcription factor involved in vascular
      quiescence. Here, we investigated the mechanism of how Ang1/Tie2 signal induces
      KLF2 expression to clarify the role of KLF2 in Ang1/Tie2 signal-mediated vascular
      quiescence. Ang1 stimulated KLF2 promoter-driven reporter gene expression in
      endothelial cells, whereas it failed when a myocyte enhancer factor 2 (MEF2)
      binding site of KLF2 promoter was mutated. Depletion of MEF2 by siRNAs abolished
      Ang1-induced KLF2 expression, indicating the requirement of MEF2 in KLF2
      induction by Ang1. Constitutive active phosphoinositide 3-kinase (PI3K) and AKT
      increased the MEF2-dependent reporter gene expression by enhancing its
      transcriptional activity and stimulated the KLF2 promoter activity cooperatively
      with MEF2. Consistently, inhibition of either PI3K or AKT and depletion of AKT
      abrogated Ang1-induced KLF2 expression. In addition, we confirmed the
      dispensability of extracellular signal-regulated kinase 5 (ERK5) for Ang1-induced
      KLF2 expression. Furthermore, depletion of KLF2 resulted in the loss of the
      inhibitory effect of Ang1 on vascular endothelial growth factor (VEGF)-mediated
      expression of vascular cell adhesion molecule-1 in endothelial cells and VEGF
      mediated monocyte adhesion to endothelial cells. Collectively, these findings
      indicate that Ang1/Tie2 signal stimulates transcriptional activity of MEF2
      through a PI3K/AKT pathway to induce KLF2 expression, which may counteract VEGF
      mediated inflammatory responses.

PMID- 19106104
TI  - Conformational variants of duplex DNA correlated with cytosine-rich chromosomal
      fragile sites.
AB  - We found that several major chromosomal fragile sites in human lymphomas,
      including the bcl-2 major breakpoint region, bcl-1 major translocation cluster,
      and c-Myc exon 1-intron 1 boundary, contain distinctive sequences of consecutive
      cytosines exhibiting a high degree of reactivity with the structure-specific
      chemical probe bisulfite. To assess the inherent structural variability of duplex
      DNA in these regions and to determine the range of structures reactive to
      bisulfite, we have performed bisulfite probing on genomic DNA in vitro and in
      situ; on duplex DNA in supercoiled and linearized plasmids; and on
      oligonucleotide DNA/DNA and DNA/2'-O-methyl RNA duplexes. Bisulfite is
      significantly more reactive at the frayed ends of DNA duplexes, which is expected
      given that bisulfite is an established probe of single-stranded DNA. We observed
      that bisulfite also distinguishes between more subtle sequence/structural
      differences in duplex DNA. Supercoiled plasmids are more reactive than linear
      DNA; and sequences containing consecutive cytosines, namely GGGCCC, are more
      reactive than those with alternating guanine and cytosine, namely GCGCGC.
      Circular dichroism and x-ray crystallography show that the GGGCCC sequence forms
      an intermediate B/A structure. Molecular dynamics simulations also predict an
      intermediate B/A structure for this sequence, and probe calculations suggest
      greater bisulfite accessibility of cytosine bases in the intermediate B/A
      structure over canonical B- or A-form DNA. Electrostatic calculations reveal that
      consecutive cytosine bases create electropositive patches in the major groove,
      predicting enhanced localization of the bisulfite anion at homo-C tracts over
      alternating G/C sequences. These characteristics of homo-C tracts in duplex DNA
      may be associated with DNA-protein interactions in vivo that predispose certain
      genomic regions to chromosomal fragility.

PMID- 19106105
TI  - FoxL2 and Smad3 coordinately regulate follistatin gene transcription.
AB  - Follistatin is a transcriptional target and a modulator of activin action.
      Through an autocrine/paracrine loop, activin controls follistatin levels and thus
      regulates its own bioavailability. In gonadotropic alphaT3-1 cells, activin
      induces follistatin transcription primarily through the action of Smad3 at an
      intronic Smad-binding element (SBE1). Using a proteomics approach, we searched
      for endogenous alphaT3-1 proteins that participate in SBE1-mediated
      transcription. We identified FoxL2, a member of the forkhead family, as a
      candidate modulator of SBE1 function. Mutations of FoxL2 are associated with the
      blepharophimosis/ptosis/epicanthus inversus syndrome characterized with
      craniofacial defects and premature ovarian failure. FoxL2 localizes to alpha
      glycoprotein subunit- and follicle-stimulating hormone beta-positive cells of the
      adult mouse pituitary and is present in alphaT3-1 and LbetaT2 cells, but its
      pituitary actions remain largely unknown. We have determined that FoxL2 binds to
      a forkhead-binding element (FKHB) located just downstream of the SBE1 site of the
      follistatin gene and functions as a Smad3 partner to drive SBE1-mediated
      transcription in alphaT3-1 cells treated with activin. Chromatin
      immunoprecipitation assays confirm that endogenous FoxL2 and Smad3 are recruited
      to the intronic enhancer of the follistatin gene where the SBE1 and FKHB sites
      are located. Exogenous FoxL2 enhances SBE1-mediated transcription, and short
      hairpin RNA-mediated knockdown of endogenous FoxL2 protein compromises this
      effect in alphaT3-1 cells. FoxL2 directly associates with Smad3 but not Smad2 or
      Smad4. This association between Smad3 and FoxL2 is mediated by the MH2 domain of
      Smad3 and is dependent on an intact forkhead domain in FoxL2. Altogether, these
      observations highlight a novel role for FoxL2 and suggest that it may function as
      a transcriptional regulator and a coordinator of Smad3 targets.

PMID- 19106107
TI  - Deoxygenated disaccharide analogs as specific inhibitors of beta1-4
      galactosyltransferase 1 and selectin-mediated tumor metastasis.
AB  - The disaccharide peracetylated GlcNAcbeta1-3Galbeta-O-naphthalenemethanol
      (disaccharide 1) diminishes the formation of the glycan sialyl Lewis X
      (Neu5Acalpha2-3Galbeta1-4(Fucalpha1-3) GlcNAc; sLe(X)) in tumor cells. Previous
      studies showed that the mechanism of action of disaccharide 1 involves three
      steps: (i) deacetylation by carboxyesterases, (ii) action as a biosynthetic
      intermediate for downstream enzymes involved in sLe(X) assembly, and (iii)
      generation of several glycans related to sLe(X). In this report, we show that
      GlcNAcbeta1-3Galbeta-O-naphthalenemethanol binds to the acceptor site of human
      beta1-4-galactosyltransferase much like the acceptor trisaccharide, GlcNAcbeta1
      2Manbeta1-6Man, which is present on N-linked glycans. The 4'-deoxy analog, in
      which the acceptor hydroxyl group was replaced by -H, did not act as a substrate
      but instead acted as a competitive inhibitor of the enzyme. The acetylated form
      of this compound inhibited sLe(X) formation in U937 monocytic leukemia cells,
      suggesting that it had inhibitory activity in vivo as well. A series of synthetic
      acetylated analogs of 1 containing -H, -F, -N(3), -NH(2), or -OCH(3) instead of
      the hydroxyl groups at C-3'- and C-4'-positions of the terminal N
      acetylglucosamine residue also blocked sLe(X) formation in cells. The reduction
      of sLe(X) by the 4'-deoxy analog also diminished experimental tumor metastasis by
      Lewis lung carcinoma in vivo. These data suggest that nonsubstrate disaccharides
      have therapeutic potential through their ability to bind to glycosyltransferases
      in vivo and to alter glycan-dependent pathologic processes.

PMID- 19106106
TI  - Inactivation of FIP200 leads to inflammatory skin disorder, but not
      tumorigenesis, in conditional knock-out mouse models.
AB  - FIP200 (focal adhesion kinase family interacting protein of 200 kDa) has been
      shown to interact with other proteins to regulate several intracellular signaling
      pathways. To study a potential role of FIP200 in tumorigenesis and possibly other
      disease processes in vivo, we created and analyzed murine mammary tumor virus-Cre
      mediated FIP200 conditional knock-out (CKO) mice. We found that deletion of
      FIP200 in mammary epithelial cells did not result in spontaneous development of
      breast cancer. Moreover, deletion of FIP200 did not further accelerate or inhibit
      lymphomagenesis induced by inactivation of p53 in mice. Interestingly, however,
      FIP200 and p53 double conditional knock-out (dCKO) mice exhibited significant
      hyperplasia of epidermis (acanthosis), thickening of the cornified layer
      (hyperkeratosis), and increased vascularity in the dermis. FIP200 CKO mice also
      showed similar, although less severe, skin defects as dCKO mice. Analyses of
      primary keratinocytes isolated from dCKO mice did not detect increased
      proliferation of these cells in vitro, suggesting that epidermis
      hyperproliferation is not epidermal cell-autonomous but may be a consequence of
      increased inflammation triggered by immune cells in vivo. Consistent with this
      possibility, we found infiltration of leukocytes including T cells, macrophages,
      and granulocytes into the dermis and epidermis, associated with activation of NF
      kappaB and increased expression of several proinflammatory cytokines and
      chemokines in skin of the dCKO mice. We further found that cultured FIP200 KO
      keratinocytes showed reduced NF-kappaB phosphorylation in response to tumor
      necrosis factor alpha stimulation, suggesting a paracrine regulation of aberrant
      NF-kappaB activation in the skin microenviroment of dCKO and FIP200 CKO mice.
      Together, these results demonstrate that ablation of FIP200, although not
      promoting tumorigenesis, can lead to skin inflammatory disorders, suggesting a
      novel function of FIP200 in the maintenance of normal skin homeostasis in vivo.

PMID- 19106108
TI  - Glycogen synthase kinase-3 regulates the phosphorylation of severe acute
      respiratory syndrome coronavirus nucleocapsid protein and viral replication.
AB  - Coronavirus (CoV) nucleocapsid (N) protein is a highly phosphorylated protein
      required for viral replication, but whether its phosphorylation and the related
      kinases are involved in the viral life cycle is unknown. We found the severe
      acute respiratory syndrome CoV N protein to be an appropriate system to address
      this issue. Using high resolution PAGE analysis, this protein could be separated
      into phosphorylated and unphosphorylated isoforms. Mass spectrometric analysis
      and deletion mapping showed that the major phosphorylation sites were located at
      the central serine-arginine (SR)-rich motif that contains several glycogen
      synthase kinase (GSK)-3 substrate consensus sequences. GSK-3-specific inhibitor
      treatment dephosphorylated the N protein, and this could be recovered by the
      constitutively active GSK-3 kinase. Immunoprecipitation brought down both N and
      GSK-3 proteins in the same complex, and the N protein could be phosphorylated
      directly at its SR-rich motif by GSK-3 using an in vitro kinase assay. Mutation
      of the two priming sites critical for GSK-3 phosphorylation in the SR-rich motif
      abolished N protein phosphorylation. Finally, GSK-3 inhibitor was found to reduce
      N phosphorylation in the severe acute respiratory syndrome CoV-infected VeroE6
      cells and decrease the viral titer and cytopathic effects. The effect of GSK-3
      inhibitor was reproduced in another coronavirus, the neurotropic JHM strain of
      mouse hepatitis virus. Our results indicate that GSK-3 is critical for CoV N
      protein phosphorylation and suggest that it plays a role in regulating the viral
      life cycle. This study, thus, provides new avenues to further investigate the
      specific role of N protein phosphorylation in CoV replication.

PMID- 19106109
TI  - p53 Oligomerization is essential for its C-terminal lysine acetylation.
AB  - Acetylation of multiple lysine residues in the p53 plays critical roles in the
      protein stability and transcriptional activity of p53. To better understand how
      p53 acetylation is regulated, we generated a number of p53 mutants and examined
      acetylation of each mutant in transfected cells. We found that p53 mutants that
      are defective in tetramer formation are also defective in C-terminal lysine
      residue acetylation. Consistently, we found that several cancer-derived p53
      mutants that bear mutations in the tetramerization domain cannot form oligomers
      and are defective in C-terminal lysine acetylation, and these mutants are
      inactive in p21 transactivation. We demonstrated that the acetyltransferase p300
      interacts with and promotes acetylation of wild-type p53 but not with any of the
      artificially generated or human cancer-derived p53 mutants that are defective in
      oligomerization. These results, combined with a computer-aided crystal structure
      analysis, suggest a model in which p53 oligomerization precedes its acetylation
      by providing docking sites for acetyltransferases.

PMID- 19106110
TI  - Platelet-derived growth factor selectively inhibits NR2B-containing N-methyl-D
      aspartate receptors in CA1 hippocampal neurons.
AB  - Platelet-derived growth factor (PDGF) beta receptor activation inhibits N-methyl
      d-aspartate (NMDA)-evoked currents in hippocampal and cortical neurons via the
      activation of phospholipase Cgamma, PKC, the release of intracellular calcium,
      and a rearrangement of the actin cytoskeleton. In the hippocampus, the majority
      of NMDA receptors are heteromeric; most are composed of 2 NR1 subunits and 2 NR2A
      or 2 NR2B subunits. Using NR2B- and NR2A-specific antagonists, we demonstrate
      that PDGF-BB treatment preferentially inhibits NR2B-containing NMDA receptor
      currents in CA1 hippocampal neurons and enhances long-term depression in an NR2B
      subunit-dependent manner. Furthermore, treatment of hippocampal slices or
      cultures with PDGF-BB decreases the surface localization of NR2B but not of NR2A
      subunits. PDGFbeta receptors colocalize to a higher degree with NR2B subunits
      than with NR2A subunits. After neuronal injury, PDGFbeta receptors and PDGF-BB
      are up-regulated and PDGFbeta receptor activation is neuroprotective against
      glutamate-induced neuronal damage in cultured neurons. We demonstrate that the
      neuroprotective effects of PDGF-BB are occluded by the NR2B antagonist, Ro25
      6981, and that PDGF-BB promotes NMDA signaling to CREB and ERK1/2. We conclude
      that PDGFbetaR signaling, by preferentially targeting NR2B receptors, provides an
      important mechanism for neuroprotection by growth factors in the central nervous
      system.

PMID- 19106111
TI  - Critical role of nucleostemin in pre-rRNA processing.
AB  - Nucleostemin is a nucleolar protein widely expressed in proliferating cells.
      Nucleostemin is involved in the regulation of cell proliferation, and both
      depletion and overexpression of nucleostemin induce cell cycle arrest through the
      p53 signaling pathway. Although the presence of p53-independent functions of
      nucleostemin has been previously suggested, the identities of these additional
      functions remained to be investigated. Here, we show that nucleostemin has a
      novel role as an integrated component of ribosome biogenesis, particularly pre
      rRNA processing. Nucleostemin forms a large protein complex (>700 kDa) that co
      fractionates with the pre-60 S ribosomal subunit in a sucrose gradient. This
      complex contains proteins related to pre-rRNA processing, such as Pes1, DDX21,
      and EBP2, in addition to several ribosomal proteins. We show that the nucleolar
      retention of DDX21 and EBP2 is dependent on the presence of nucleostemin in the
      nucleolus. Furthermore, the knockdown of nucleostemin delays the processing of 32
      S pre-rRNA into 28 S rRNA. This is accompanied by a substantial decrease of
      protein synthesis as well as the levels of rRNAs and some mRNAs. In addition,
      overexpressed nucleostemin significantly promotes the processing of 32 S pre
      rRNA. Collectively, these biochemical and functional studies demonstrate a novel
      role of nucleostemin in ribosome biogenesis. This is a key aspect of the role of
      nucleostemin in regulating cell proliferation.

PMID- 19106112
TI  - Coupling factor 6 enhances Src-mediated responsiveness to angiotensin II in
      resistance arterioles and cells.
AB  - AIMS: Coupling factor 6 (CF6) induces hypertension by attenuating the endothelial
      generation of prostacyclin. However, intracellular signalling of CF6 in the
      resistance arteriole vascular smooth muscle cells (VSMCs) that are directly
      related to vasoconstriction has not been determined. Here we investigated the
      direct effect of exogenous CF6 on Ca2+ signalling in cultured VSMCs and the in
      vivo role of endogenous CF6 in the genesis of hypertension using CF6 transgenic
      (TG) mice. METHODS AND RESULTS: CF6 induced a monophasic increase in the
      intracellular free Ca2+ concentration ([Ca2+]i) through nifedipine-sensitive Ca2+
      channels in A7r5 cells, a cell line of VSMCs, and enhanced the angiotensin II
      induced spike phase of [Ca2+]i to a greater degree in VSMCs derived from
      spontaneously hypertensive rats (SHRs). In the mesenteric arterioles obtained
      from CF6-TG mice that manifested hypertension, angiotensin II-induced
      vasoconstriction was enhanced, compared with wild-type mice, and its enhancement
      was abolished by an anti-CF6 antibody. Pre-treatment with PP1, a tyrosine kinase
      c-Src inhibitor, blocked CF6-induced increase in Ca2+ signalling in VSMCs and
      vasoconstriction in TG mice. The receptor of CF6 was F1 motor of adenosine
      triphosphate (ATP) synthase with a higher affinity in SHRs. CF6 decreased
      intracellular pH via activation of ATPase activity and led to c-Src activation to
      a greater degree in SHR-derived VSMCs. CONCLUSION: CF6 causes hypertension by
      directly enhancing Ca2+ signalling in VSMCs and vasoconstriction in the
      mesenteric arteriolar network via c-Src activation.

PMID- 19106113
TI  - Keratinocyte growth factor and its receptor in human ovaries from fetuses, girls
      and women.
AB  - Keratinocyte growth factor (KGF) promotes growth of rat pre-antral follicles.
      There is limited information regarding its presence or that of its unique
      receptor (KGFR) in human ovaries, specifically in pre-antral follicles. The aim
      of the study was to investigate the expression of KGF and KGFR in ovarian samples
      from human fetuses and girls/women. The samples were prepared for
      immunohistochemical study of the KGF protein and for in situ hybridization to
      localize mRNA transcripts of KGFR. Total RNA was extracted from frozen ovarian
      samples, and the expression of KGF mRNA transcripts was investigated by reverse
      transcriptase polymerase chain reaction. In both fetuses and girls/women, the
      protein for KGF was detected from primordial stages in oocytes, granulosa cells
      (GCs) and stroma cells. Its mRNA transcripts were also detected in all extracts.
      The mRNA transcripts for KGFR were detected mainly in stroma cells in ovarian
      samples from both sources; in 10% of the samples, follicular staining was noted
      also in oocytes and GCs. Further studies adding KGF to the culture medium are
      needed to elucidate its putative role in human primordial follicle activation.

PMID- 19106115
TI  - Mechanism of vitamin D receptor inhibition of cholesterol 7alpha-hydroxylase gene
      transcription in human hepatocytes.
AB  - Lithocholic acid (LCA) is a potent endogenous vitamin D receptor (VDR) ligand. In
      cholestasis, LCA levels increase in the liver and intestine. The objective of
      this study is to test the hypothesis that VDR plays a role in inhibiting
      cholesterol 7alpha-hydroxylase (CYP7A1) gene expression and bile acid synthesis
      in human hepatocytes. Immunoblot analysis has detected VDR proteins in the
      nucleus of the human hepatoma cell line HepG2 and human primary hepatocytes.
      1alpha, 25-Dihydroxy-vitamin D(3) or LCA acetate-activated VDR inhibited CYP7A1
      mRNA expression and bile acid synthesis, whereas small interfering RNA to VDR
      completely abrogated VDR inhibition of CYP7A1 mRNA expression in HepG2 cells.
      Electrophoretic mobility shift assay and mutagenesis analyses have identified the
      negative VDR response elements that bind VDR/retinoid X receptor alpha in the
      human CYP7A1 promoter. Mammalian two-hybrid, coimmunoprecipitation, glutathione S
      transferase pull-down, and chromatin immunoprecipitation assays show that ligand
      activated VDR specifically interacts with hepatocyte nuclear factor 4alpha
      (HNF4alpha) to block HNF4alpha interaction with coactivators or to compete with
      HNF4alpha for coactivators or to compete for binding to CYP7A1 chromatin, which
      results in the inhibition of CYP7A1 gene transcription. This study shows that VDR
      is expressed in human hepatocytes and may play a critical role in the inhibition
      of bile acid synthesis, thus protecting liver cells during cholestasis.

PMID- 19106114
TI  - Conservation of mechanisms mediating gonadotrophin-releasing hormone 1
      stimulation of human luteinizing hormone beta subunit transcription.
AB  - Gonadotrophin-releasing hormone (GNRH1) regulates pituitary luteinizing hormone
      (LH). Previous studies have delineated a mechanism for GNRH1-induced LHbeta
      subunit gene (Lhb) transcription, the rate-limiting step in LH production. GNRH1
      induces expression of early growth response 1 (EGR1), which interacts with
      steroidogenic factor 1 (SF1) and paired-like homeodomain transcription factor 1
      (PITX1) to regulate Lhb promoter activity. Though the cis-elements for these
      factors are conserved across species, regulation of human LHB transcription has
      not been thoroughly investigated. We therefore characterized LHB transcriptional
      regulation by GNRH1 using promoter-reporter analyses in LbetaT2 cells. GNRH1
      stimulated LHB transcription via an extracellular signal-regulated kinase 1/2
      pathway. EGR1 bound to two binding sites on the LHB promoter and this binding was
      increased by GNRH1. Mutation of either site or knockdown of endogenous EGR1
      decreased basal and/or GNRH1-regulated promoter activity. The human LHB promoter
      also contains low and high affinity SF1 binding sites. Mutation of these elements
      or depletion of endogenous SF1 impaired basal and ligand-induced transcription.
      Knockdown of PITX1 or PITX2 isoforms impaired GNRH1 induction, and endogenous
      PITX1 bound to the candidate PITX binding site on the LHB promoter. Thus, the
      mechanism described for GNRH1 regulation of Lhb in other species is largely
      conserved for human LHB. We also uncover a previously unappreciated role for
      PITX2 isoforms in this process.

PMID- 19106116
TI  - 5'-aminocarbonyl phosphonates as new zidovudine depot forms: antiviral
      properties, intracellular transformations, and pharmacokinetic parameters.
AB  - The main disadvantages of 3'-azido-3'-deoxythymidine (zidovudine, AZT), the most
      common anti-HIV drug, are toxicity and a short half-life in the organism. The
      introduction of an H-phosphonate group into the AZT 5' position resulted in
      significant improvement of its therapeutic properties and allowed a new anti-HIV
      drug, Nikavir (AZT H-phosphonate). In this work, we described a new group of AZT
      derivatives, namely, AZT 5'-aminocarbonylphosphonates. The synthesized compounds
      displayed antiviral properties in cell cultures infected with HIV-1 and the
      capacity to release the active nucleoside in animals (rabbits and dogs) in a dose
      dependent manner. The compounds were less toxic in MT-4 and HL-60 cell cultures
      and experimental animals compared with AZT. Major metabolites found in MT-4 cells
      after their incubation with AZT 5'-aminocarbonylphosphonate 1 were AZT and AZT 5'
      phosphate (25 and 55%, respectively). Among the tested compounds, phosphonate 1
      was the most effective AZT donor, and its longest t(1/2) and T(max) values in the
      line phosphonate 1--AZT H-phosphonate--AZT imply that compound 1 is an extended
      depot form of AZT. Although bioavailability of AZT after oral administration of
      phosphonate 1 was lower than those of AZT H-phosphonate and AZT (8 against 14 and
      49%), we expect that this reduction would not cause essential decrease of
      antiviral activity but noticeably decrease toxicity as a result of gradual
      accumulation of AZT in blood and the absence of sharp difference between C(max)
      and C(min). Such a combination of properties makes the compounds of this group
      promising for further studies as extended-release forms of AZT.

PMID- 19106118
TI  - Measurement of changes in cytosolic Ca2+ in Arabidopsis guard cells and mesophyll
      cells in response to blue light.
AB  - Phototropins (phot1 and phot2) are blue light (BL) receptors that mediate
      responses including phototropism, chloroplast movement and stomatal opening, and
      increased cytosolic Ca(2+). BL absorbed by phototropins activates plasma membrane
      H(+)-ATPase in guard cells, resulting in membrane hyperpolarization, and drives
      K(+) uptake and stomatal opening. However, it is unclear whether the phototropin
      mediated Ca(2+) increase activates the H(+)-ATPase. Here, we determined cytosolic
      Ca(2+) concentrations in guard cell protoplasts (GCPs) from Arabidopsis
      transformed with aequorin. Cytosolic Ca(2+) increased rapidly in response to BL
      in GCPs from both the wild type and phot1 phot2 double mutants, but was mostly
      suppressed by an inhibitor of photosynthetic electron flow (DCMU). With depleted
      external K(+), we observed another slower Ca(2+) increase, which was phototropin-
      dependent. Fusicoccin, a H(+)-ATPase activator, mimicked the effect of BL. The
      slow Ca(2+) increase thus appears to result from membrane hyperpolarization. The
      slow Ca(2+) increase was suppressed by external K(+) and was restored by blockers
      of inward-rectifying K(+) channels, CsCl and tetraethylammonium, suggesting the
      preferential uptake of K(+) over Ca(2+). Such efficient K(+) uptake in response
      to BL was not found in mesophyll cells. Both the fast and the slow Ca(2+)
      increases were inhibited by Ca(2+) channel blockers (CoCl(2) and LaCl(3)) and a
      chelating agent (EGTA). These results indicate that the phototropin-mediated
      Ca(2+) increase was not observed prior to H(+)-ATPase activation in guard cells
      and that Ca(2+) entered guard cells via Ca(2+) channels through photosynthesis
      and phototropin-mediated membrane hyperpolarization.

PMID- 19106117
TI  - Epidemiology of critically ill children in England and Wales: incidence,
      mortality, deprivation and ethnicity.
AB  - OBJECTIVE: The purpose of this work was to investigate the incidence rate for
      admission and mortality of children receiving paediatric intensive care in
      relation to socioeconomic status and ethnicity in England and Wales. DESIGN:
      National cohort of sequential hospital admissions. SETTING: Twenty nine
      paediatric intensive care units in England and Wales. PARTICIPANTS: All children
      aged under 16 years admitted to paediatric intensive care in the 4 years 2004
      2007. MAIN OUTCOME MEASURES: Incidence rates for admission and odds ratios (OR)
      for risk-adjusted mortality by an area based measure of deprivation (Townsend
      score) and ethnic group (south Asian vs non-south Asian determined using two-name
      analysis algorithms). RESULTS: The incidence for south Asian children was higher
      than that of non-south Asian children (138 vs 95/100,000, incidence rate ratio
      1.36, 95% CI 1.32 to 1.40). The age-sex standardised incidence for children
      admitted to paediatric intensive care ranged from 69/100,000 in the least
      deprived fifth of the population to 124/100,000 in the most deprived fifth. The
      risk-adjusted OR for mortality for south Asian children was 1.36 (95% CI 1.18 to
      1.57) overall, rising to 2.40 (95% CI 1.40 to 4.10) in the least deprived fifth
      of the population when a statistical interaction term for deprivation was
      included. CONCLUSIONS: In England and Wales, the admission rate to paediatric
      intensive care is higher for children from more deprived areas and 36% higher for
      children from the south Asian population. Risk-adjusted mortality increases in
      south Asian children as deprivation decreases.

PMID- 19106119
TI  - Alterations in detergent-resistant plasma membrane microdomains in Arabidopsis
      thaliana during cold acclimation.
AB  - Microdomains in the plasma membrane (PM) have been proposed to be involved in
      many important cellular events in plant cells. To understand the role of PM
      microdomains in plant cold acclimation, we isolated the microdomains as detergent
      resistant plasma membrane fractions (DRMs) from Arabidopsis seedlings and
      compared lipid and protein compositions before and after cold acclimation. The
      DRM was enriched in sterols and glucocerebrosides, and the proportion of free
      sterols in the DRM increased after cold acclimation. The protein-to-lipid ratio
      in the DRM was greater than that in the total PM fraction. The protein amount
      recovered in DRMs decreased gradually during cold acclimation. Cold acclimation
      further resulted in quantitative changes in DRM protein profiles. Subsequent mass
      spectrometry and Western blot analyses revealed that P-type H(+)-ATPases,
      aquaporins and endocytosis-related proteins increased and, conversely, tubulins,
      actins and V-type H(+)-ATPase subunits decreased in DRMs during cold acclimation.
      Functional categorization of cold-responsive proteins in DRMs suggests that plant
      PM microdomains function as platforms of membrane transport, membrane trafficking
      and cytoskeleton interaction. These comprehensive changes in microdomains may be
      associated with cold acclimation of Arabidopsis.

PMID- 19106120
TI  - AnnotationSketch: a genome annotation drawing library.
AB  - SUMMARY: To analyse the vast amount of genome annotation data available today, a
      visual representation of genomic features in a given sequence range is required.
      We developed a C library which provides layout and drawing capabilities for
      annotation features. It supports several common input and output formats and can
      easily be integrated into custom C applications. To exemplify the use of
      AnnotationSketch in other languages, we provide bindings to the scripting
      languages Ruby, Python and Lua. AVAILABILITY: The software is available under an
      open-source license as part of GenomeTools
      (http://genometools.org/annotationsketch.html).

PMID- 19106121
TI  - arrayQualityMetrics--a bioconductor package for quality assessment of microarray
      data.
AB  - SUMMARY: The assessment of data quality is a major concern in microarray
      analysis. arrayQualityMetrics is a Bioconductor package that provides a report
      with diagnostic plots for one or two colour microarray data. The quality metrics
      assess reproducibility, identify apparent outlier arrays and compute measures of
      signal-to-noise ratio. The tool handles most current microarray technologies and
      is amenable to use in automated analysis pipelines or for automatic report
      generation, as well as for use by individuals. The diagnosis of quality remains,
      in principle, a context-dependent judgement, but our tool provides powerful,
      automated, objective and comprehensive instruments on which to base a decision.
      AVAILABILITY: arrayQualityMetrics is a free and open source package, under LGPL
      license, available from the Bioconductor project at www.bioconductor.org. A users
      guide and examples are provided with the package. Some examples of HTML reports
      generated by arrayQualityMetrics can be found at http://www.microarray
      quality.org

PMID- 19106122
TI  - Role of activated carbon fabric mask to prevent lead absorption--a short report.
AB  - An attempt was made to study the usefulness of activated carbon fabric (ACF) mask
      to prevent lead absorption. Indigenous ACF masks were provided to eight workers
      involved in the manufacture of batteries. Their blood lead levels were determined
      before and after using these masks. There was a substantial decrease in blood
      lead level after using the mask among those who were under treatment for high
      blood lead levels. Three workers who were not under treatment for lead also
      showed a decrease in blood lead level, after using this ACF mask, suggesting the
      usefulness of ACF in preventing further exposure. Such a study has not been
      reported anywhere in the available literature and similar such studies with more
      number of masks is necessary to evaluate its effectiveness.

PMID- 19106123
TI  - The importance of controlling carbon not emissions or mpg.
AB  - In management of carbon dioxide concentrations in the atmosphere, the authors
      argue that it is far superior to control upstream where the carbon leaves the
      ground in a limited number of places than further downstream as carbon dioxide is
      released in a myriad of locations. The authors note that none of the proposals
      being discussed politically assure this, and they control sector by sector,
      allowing undesirable room for special interests to be excluded from control.

PMID- 19106124
TI  - Histopathological changes in the liver and kidney tissues of Wistar albino rat
      exposed to fenitrothion.
AB  - The aim of this study was to investigate the dose-related effects of fenitrothion
      (FNT) on the liver and kidney. The study was conducted on 8-week-old male Wistar
      rats that were divided into four groups (three experimental groups and one
      control group) and were treated orally with different doses (25, 50, 100 mg/kg)
      of FNT for 28 consecutive days. After treatment, the rats were anesthetized with
      ether and liver and kidney samples were taken for histological studies. The
      results showed that the histopathological changes in the liver were mainly
      represented by parenchymatous degeneration of hepatocytes with mild necrosis,
      leukocytic infiltration in the portal area, severe congestion, and hemorrhage.
      These changes were dose dependent. Marked tubular dilation, hydropic degeneration
      in tubular epithelium, moderate congestion, and hemorrhage in the cortical and
      medulla part of the kidney were recorded. Histopathologic examination of the
      liver and kidney indicated a significant injury only in rats receiving 100 mg/kg
      FNT.

PMID- 19106126
TI  - Effect of vitamin E on reproductive function in the mice treated with 2,3,7,8
      tetrachlorodibenzo-p-dioxin.
AB  - The study was conducted to determine the effects of vitamin E on reproductive
      performance in mice treated with 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). The
      75 female and 40 male mice were randomly assigned into five groups. The levels of
      both TCDD and vitamin E given by gavage were 0 and 0 (Control group), 100 and 0
      (experimental group I), 100 and 20 (experimental group II), 100 and 100
      (experimental group III), and 100 ng/kg/day and 500 mg/kg/day (experimental group
      IV), respectively. Males and females were mixed to mate at the ratio of 1:2 after
      4-week experiment. The gavage treatments were continued until the end of
      gestation in female mice after mating. The results showed that the litter number,
      survival rate, and body weight at birth of offspring in experimental group I had
      significantly decreased, and the females' pregnancy rate and pup sex ratio in
      experimental group I had the decreasing tendencies when compared with the control
      group. The litter number in experimental group III, survival rate in experimental
      group II and III, body weight at birth in experimental group III and IV exhibited
      significant increase compared with experimental group I. The female pregnancy
      rate in both experimental group III and IV recovered to 100%, but there were no
      significant differences when compared with experimental group I. The pups' sex
      ratio had a gradually increasing tendency with increase of vitamin E level, but
      there was no significant difference among experimental group I-IV. The results
      suggest that TCDD could induce reproductive toxicity in mice, whereas vitamin E
      alleviated adverse effects on reproductive performance in mice caused by TCDD.

PMID- 19106125
TI  - Induction of micronuclei in rat bone marrow after chronic exposure to lead
      acetate trihydrate.
AB  - Lead increasingly contributes to pollution of the environment and may play a role
      in the development of adverse effects in the human and animal body. Data
      concerning its mutagenic, clastogenic, and carcinogenic properties have been
      conflicting. In this study, we evaluated the frequency of micronuclei in bone
      marrow erythrocytes of rats treated with lead acetate trihydrate. Outbred Wistar
      rats were exposed to a daily dose of 100 mg/L drinking water for 125 days. The
      mean value of the total number of micronuclei observed in polychromatic
      erythrocytes of female rats was significantly higher than that found in the
      control group (13.375 +/- 2.722 against 9.625 +/- 3.204 micronuclei/1000 cells; P
      = 0.024 in ANOVA). In exposed female animals, no significant reduction of the
      ratio of polychromatic to normochromatic erythrocytes was observed (0.990 +/-
      0.228 against 1.208 +/- 0.195; P = 0.060 in ANOVA). The effects of lead acetate
      trihydrate in male rats are both cytotoxic and genotoxic because of a decrease in
      ratio of polychromatic to normochromatic erythrocytes (0.715 +/- 0.431 against
      1.343 +/- 0.306; P = 0.023, ANOVA followed by Tukey test) and an increase in
      frequency of micronucleated polychromatic erythrocytes (24.167 +/- 7.859 against
      4.0 +/- 4.528 micronuclei/1000 cells; P < or = 0.001, ANOVA followed by Tukey
      test), respectively.

PMID- 19106127
TI  - Urinary level of nickel and acute leukaemia in Chinese children.
AB  - The 8-hydroxy-2'-deoxyguanosine (8-OHdG), an oxidized nucleoside of DNA, not only
      is a widely used biomarker for the measurement of endogenous oxidative DNA damage
      but might also be a risk factor for many diseases including cancer. Metal
      exposure may play an important role in oxidative DNA damage among children.
      However, few studies on urinary 8-OHdG and metals have been conducted in children
      with acute leukemia. In the present study, urinary Ni and 8-OHdG were examined in
      116 children with acute leukaemia (94 acute lymphoid leukaemia [ALL] and 22 acute
      myeloid leukaemia [AML]) and 51 healthy child controls. Our result showed that
      urinary Ni in acute leukaemia patients (ALL: 68.40 +/- 133.98, AML: 41.48 +/-
      76.31 ng/mg creatinine) was significantly higher than that in controls (62.47 +/-
      124.90 vs 17.63 +/- 46.17 ng/mg creatinine, P < 0.05). Similarly, the pretherapy
      level of urinary 8-OHdG in patients (ALL: 11.83 +/- 16.23, AML: 12.36 +/- 11.36
      ng/mg creatinine) was significantly elevated compared with controls (11.92 +/-
      15.42 vs 4.03 +/- 4.70 ng/mg creatinine, P < 0.05). Moreover, urinary 8-OHdG and
      urinary Ni showed a weak but significant association with increased risk of
      childhood leukaemia. The present study suggests that Ni may be an etiologic
      factor for childhood acute leukaemia by oxidative DNA damage.

PMID- 19106128
TI  - Lead-induced oxidative stress adversely affects health of the occupational
      workers.
AB  - Lead is a persistent toxic metal and associated with impairment of various body
      functions in occupational workers. The main objective was to determine the lead
      induced oxidative stress and adverse health effects by biochemical markers in
      industrial workers. One hundred and forty-eight males consisting of 87 lead
      exposed industrial workers and 61 controls were included. Blood lead level (BLL)
      was determined on a 3010B ESA lead analyzer. Blood complete counts were done on a
      hematology analyzer. Biochemical markers including serum uric acid, urea,
      creatinine, phosphate, alanine aminotransferase (ALT), and gamma
      glutamyltransferase (GGT) were measured on a Selectra E auto analyzer. Serum
      malondialdehyde (MDA) was measured spectrophotometrically and C-reactive protein
      (CRP) on Immulite-1000. Results revealed that lead-exposed workers had
      significantly high BLLs, median (range), 29.1 (9.0-61.1) microg/dL compared with
      controls, 8.3 (1.0-21.7) microg/dL. Oxidative stress (MDA, GGT) and inflammatory
      markers (high-sensitivity CRP) were significantly increased (P < or = 0.05).
      Blood pressure was raised, whereas hemoglobin was decreased in exposed group (P <
      or = 0.002). Serum urea, uric acid, phosphate, and ALT were significantly raised
      in lead-exposed workers (P < or = 0.001). Serum albumin, total proteins, and
      glomerular filtration rate (GFR) were decreased. Blood lead showed a significant
      positive correlation with serum GGT (r = 0.63), MDA (r = 0.71), CRP (r = 0.75),
      urea (r = 0.34), creatinine (r = 0.51), and uric acid (r = 0.29) (P < or = 0.01).
      It is concluded that lead exposure increases oxidative stress that correlates
      with adverse changes in hematological, renal, and hepatic function in the
      occupational workers. Elevated blood lead has positive correlation with oxidative
      stress, inflammatory and biochemical markers that might be used to detect
      impairment in the body function in lead exposed workers.

PMID- 19106129
TI  - Ethics Man. "But you're not a doctor!".

PMID- 19106130
TI  - Perinatal mortality in Netherlands third worst in Europe.

PMID- 19106131
TI  - US Institute of Medicine calls for greater commitment to global health.

PMID- 19106132
TI  - US Supreme Court says smokers can sue over "light" cigarettes.

PMID- 19106134
TI  - Bush administration issues rule to protect health workers who object to medical
      procedures.

PMID- 19106136
TI  - Fish oil and secondary prevention of cardiovascular disease.

PMID- 19106137
TI  - Effect of fish oil on arrhythmias and mortality: systematic review.
AB  - OBJECTIVE: To synthesise the literature on the effects of fish oil
      docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA)-on mortality and
      arrhythmias and to explore dose response and formulation effects. DESIGN:
      Systematic review and meta-analysis. DATA SOURCES: Medline, Embase, the Cochrane
      Library, PubMed, CINAHL, IPA, Web of Science, Scopus, Pascal, Allied and
      Complementary Medicine, Academic OneFile, ProQuest Dissertations and Theses,
      Evidence-Based Complementary Medicine, and LILACS. Studies reviewed Randomised
      controlled trials of fish oil as dietary supplements in humans. DATA EXTRACTION:
      The primary outcomes of interest were the arrhythmic end points of appropriate
      implantable cardiac defibrillator intervention and sudden cardiac death. The
      secondary outcomes were all cause mortality and death from cardiac causes.
      Subgroup analyses included the effect of formulations of EPA and DHA on death
      from cardiac causes and effects of fish oil in patients with coronary artery
      disease or myocardial infarction. DATA SYNTHESIS: 12 studies totalling 32 779
      patients met the inclusion criteria. A neutral effect was reported in three
      studies (n=1148) for appropriate implantable cardiac defibrillator intervention
      (odds ratio 0.90, 95% confidence interval 0.55 to 1.46) and in six studies (n=31
      111) for sudden cardiac death (0.81, 0.52 to 1.25). 11 studies (n=32 439 and n=32
      519) provided data on the effects of fish oil on all cause mortality (0.92, 0.82
      to 1.03) and a reduction in deaths from cardiac causes (0.80, 0.69 to 0.92). The
      dose-response relation for DHA and EPA on reduction in deaths from cardiac causes
      was not significant. CONCLUSIONS: Fish oil supplementation was associated with a
      significant reduction in deaths from cardiac causes but had no effect on
      arrhythmias or all cause mortality. Evidence to recommend an optimal formulation
      of EPA or DHA to reduce these outcomes is insufficient. Fish oils are a
      heterogeneous product, and the optimal formulations for DHA and EPA remain
      unclear.

PMID- 19106138
TI  - Should the contraceptive pill be available without prescription? Yes.

PMID- 19106139
TI  - Should the contraceptive pill be available without prescription? No.

PMID- 19106141
TI  - Pseudocounts for transcription factor binding sites.
AB  - To represent the sequence specificity of transcription factors, the position
      weight matrix (PWM) is widely used. In most cases, each element is defined as a
      log likelihood ratio of a base appearing at a certain position, which is
      estimated from a finite number of known binding sites. To avoid bias due to this
      small sample size, a certain numeric value, called a pseudocount, is usually
      allocated for each position, and its fraction according to the background base
      composition is added to each element. So far, there has been no consensus on the
      optimal pseudocount value. In this study, we simulated the sampling process by
      artificially generating binding sites based on observed nucleotide frequencies in
      a public PWM database, and then the generated matrix with an added pseudocount
      value was compared to the original frequency matrix using various measures.
      Although the results were somewhat different between measures, in many cases, we
      could find an optimal pseudocount value for each matrix. These optimal values are
      independent of the sample size and are clearly correlated with the entropy of the
      original matrices, meaning that larger pseudocount vales are preferable for less
      conserved binding sites. As a simple representative, we suggest the value of 0.8
      for practical uses.

PMID- 19106140
TI  - Structural studies of type I topoisomerases.
AB  - Topoisomerases are ubiquitous proteins found in all three domains of life. They
      change the topology of DNA via transient breaks on either one or two of the DNA
      strands to allow passage of another single or double DNA strand through the
      break. Topoisomerases are classified into two types: type I enzymes cleave one
      DNA strand and pass either one or two DNA strands through the break before
      resealing it, while type II molecules cleave both DNA strands in concert and pass
      another double strand through the break followed by religation of the double
      strand break. Here we review recent work on the structure of type I enzymes.
      These structural studies are providing atomic details that, together with the
      existing wealth of biochemical and biophysical data, are bringing our
      understanding of the mechanism of action of these enzymes to the atomic level.

PMID- 19106142
TI  - Analysis of natural variants of the hepatitis C virus internal ribosome entry
      site reveals that primary sequence plays a key role in cap-independent
      translation.
AB  - The HCV internal ribosome entry site (IRES) spans a region of approximately 340
      nt that encompasses most of the 5' untranslated region (5'UTR) of the viral mRNA
      and the first 24-40 nt of the core-coding region. To investigate the implication
      of altering the primary sequence of the 5'UTR on IRES activity, naturally
      occurring variants of the 5'UTR were isolated from clinical samples and analyzed.
      The impact of the identified mutations on translation was evaluated in the
      context of RLuc/FLuc bicistronic RNAs. Results show that depending on their
      location within the RNA structure, these naturally occurring mutations cause a
      range of effects on IRES activity. However, mutations within subdomain IIId
      hinder HCV IRES-mediated translation. In an attempt to explain these data, the
      dynamic behavior of the subdomain IIId was analyzed by means of molecular
      dynamics (MD) simulations. Despite the loss of function, MD simulations predicted
      that mutant G266A/G268U possesses a structure similar to the wt-RNA. This
      prediction was validated by analyzing the secondary structure of the isolated
      IIId RNAs by circular dichroism spectroscopy in the presence or absence of Mg(2+)
      ions. These data strongly suggest that the primary sequence of subdomain IIId
      plays a key role in HCV IRES-mediated translation.

PMID- 19106144
TI  - Sensitive isothermal detection of nucleic-acid sequence by primer generation
      rolling circle amplification.
AB  - A simple isothermal nucleic-acid amplification reaction, primer generation
      rolling circle amplification (PG-RCA), was developed to detect specific nucleic
      acid sequences of sample DNA. This amplification method is achievable at a
      constant temperature (e.g. 60 degrees C) simply by mixing circular single
      stranded DNA probe, DNA polymerase and nicking enzyme. Unlike conventional
      nucleic-acid amplification reactions such as polymerase chain reaction (PCR),
      this reaction does not require exogenous primers, which often cause primer
      dimerization or non-specific amplification. Instead, 'primers' are generated and
      accumulated during the reaction. The circular probe carries only two sequences:
      (i) a hybridization sequence to the sample DNA and (ii) a recognition sequence of
      the nicking enzyme. In PG-RCA, the circular probe first hybridizes with the
      sample DNA, and then a cascade reaction of linear rolling circle amplification
      and nicking reactions takes place. In contrast with conventional linear rolling
      circle amplification, the signal amplification is in an exponential mode since
      many copies of 'primers' are successively produced by multiple nicking reactions.
      Under the optimized condition, we obtained a remarkable sensitivity of 84.5 ymol
      (50.7 molecules) of synthetic sample DNA and 0.163 pg (approximately 60
      molecules) of genomic DNA from Listeria monocytogenes, indicating strong
      applicability of PG-RCA to various molecular diagnostic assays.

PMID- 19106145
TI  - Thinking from inside the box.

PMID- 19106143
TI  - The A-rich RNA sequences of HIV-1 pol are important for the synthesis of viral
      cDNA.
AB  - The bias of A-rich codons in HIV-1 pol is thought to be a record of
      hypermutations in viral genomes that lack biological functions. Bioinformatic
      analysis predicted that A-rich sequences are generally associated with minimal
      local RNA structures. Using codon modifications to reduce the amount of A-rich
      sequences within HIV-1 genomes, we have reduced the flexibility of RNA sequences
      in pol to analyze the functional significance of these A-rich 'structurally poor'
      RNA elements in HIV-1 pol. Our data showed that codon modification of HIV-1
      sequences led to a suppression of virus infectivity by 5-100-fold, and this
      defect does not correlate with, viral entry, viral protein expression levels,
      viral protein profiles or virion packaging of genomic RNA. Codon modification of
      HIV-1 pol correlated with an enhanced dimer stability of the viral RNA genome,
      which was associated with a reduction of viral cDNA synthesis both during HIV-1
      infection and in a cell free reverse transcription assay. Our data provided
      direct evidence that the HIV-1 A-rich pol sequence is not merely an evolutionary
      artifact of enzyme-induced hypermutations, and that HIV-1 has adapted to rely on
      A-rich RNA sequences to support the synthesis of viral cDNA during reverse
      transcription, highlighting the utility of using 'structurally poor' RNA domains
      in regulating biological process.

PMID- 19106146
TI  - Outcome predictors and impact of central node dissection and radiometabolic
      treatments in papillary thyroid cancers < or =2 cm.
AB  - The incidence of papillary thyroid cancer (PTC) is rapidly growing, the recorded
      increase being mainly related to tumors < or =2 cm. The re-classification of
      tumors >1 and < or =2 cm limited to the thyroid from the T2 to the T1 category
      triggered some concerns about their best management. In order to identify
      possible predictors of disease outcome, several clinico-pathological features
      were analyzed by uni- and multivariate analyses in a retrospective consecutive
      series of 251 PTCs < or =2 cm. Moreover, since 37% of cases were submitted to
      prophylactic central compartment node dissection (CLND, VI-VII levels) and
      radioiodine ablation was performed only when the tumor had an extrathyroidal
      extension, the impact of these therapeutic tools on the final outcome was
      evaluated. Among all outcome predictors analyzed, only lymph node metastases and
      extracapsular invasion were strongly associated with persistence/recurrence. It
      is worth noting that neither age nor tumor size was a significant indicator of
      the outcome. Interestingly, as far as the therapeutic interventions are
      concerned, CLND was strongly associated with remission, whereas radioiodine
      ablation did not influence the outcome. In conclusion, present results confirm
      the prognostic influence of node metastases and extra-thyroidal invasion,
      indicating the need for aggressive treatment in tumors extending beyond the
      capsule. On the contrary, all pT1N0 tumors, regardless of the diameter, the
      number of intrathyroidal foci, and the age can be effectively treated only by
      surgery. The major impact of prophylactic CLND on prognosis suggests to routinely
      associate it to total thyroidectomy in cases with a preoperative diagnosis of
      malignancy.

PMID- 19106147
TI  - JNK inhibition sensitises hepatocellular carcinoma cells but not normal
      hepatocytes to the TNF-related apoptosis-inducing ligand.
AB  - BACKGROUND: cJun terminal kinase (JNK) is constitutively activated in most
      hepatocellular carcinomas (HCCs), yet its exact role in carcinogenesis remains
      controversial. While tumour necrosis factor (TNF)-related apoptosis-inducing
      ligand (TRAIL) is known as a major mediator of acquired immune tumour
      surveillance, and is currently being tested in clinical trials as a novel cancer
      therapy, the resistance of many tumours to TRAIL and concerns about its toxicity
      in vivo represent obstacles to its clinical application. In this study we
      investigated whether JNK activity in HCC could contribute to the resistance to
      apoptosis in these tumours. METHODS: The effect of JNK/Jun inhibition on receptor
      mediated apoptosis was analysed by pharmacological inhibition or RNA interference
      in cancer cells and non-tumour cells isolated from human liver or transgenic mice
      lacking a phosphorylation site for Jun. RESULTS: JNK inhibition caused cell cycle
      arrest, enhanced caspase recruitment, and greatly sensitised HCC cells but not
      normal hepatocytes to TRAIL. TRAIL-induced activation of JNK could be effectively
      interrupted by administration of the JNK inhibitor SP600125. CONCLUSIONS:
      Expression and TRAIL-dependent feedback activation of JNK likely represent a
      mechanism by which cancer cells escape TRAIL-mediated tumour surveillance. JNK
      inhibition might represent a novel strategy for specifically sensitising HCC
      cells to TRAIL thus opening promising therapeutic perspectives for safe and
      effective use of TRAIL in cancer treatment.

PMID- 19106148
TI  - "It has to speak to people's everyday life...": qualitative study of men and
      women's willingness to participate in a non-medical approach to Chlamydia
      trachomatis screening.
AB  - OBJECTIVE: To explore the factors associated with men and women's willingness to
      provide a urine sample for Chlamydia trachomatis screening in various non-medical
      settings. METHODS: Men and women aged 16-24 years attending non-medical settings
      were invited to participate in urine-based screening and later to participate in
      a follow-up in-depth interview. Participant observation techniques were also used
      to collect data on young people's response to the offer of screening. RESULTS:
      The views of 24 men and women revealed three themes in relation to willingness to
      participate, particularly among men: their raised awareness of chlamydia,
      particularly its asymptomatic nature; the convenience of the offer; and the "non
      medical" nature of the screening. In contrast, women more often felt the public
      nature of the settings inhibited them from agreeing to take the test and, thus,
      acted as a barrier to their willingness to participate in screening. CONCLUSIONS:
      The gender difference in willingness to participate in non-medical screening
      suggests that extending the reach of screening could certainly assist in bringing
      more young men into screening but may not necessarily destigmatise screening for
      women. As such, the potential benefits to men must be considered in the context
      of the potential psychosocial harms to women.

PMID- 19106149
TI  - Abnormal optic disc and retinal vessels in children with surgically treated
      hydrocephalus.
AB  - AIMS: To investigate the morphology of the optic disc and retinal vessels in
      children with surgically treated hydrocephalus. METHODS: A prospective,
      population-based study was performed in 69 children (median age 9.6 years) with
      early surgically treated hydrocephalus. All children were examined by
      ophthalmoscopy. Additionally, optic disc and retinal vessel morphology was
      evaluated in 55 children by digital image analysis of ocular fundus photographs.
      RESULTS: Optic atrophy was found in 10 of 69 children (14%). In comparison with a
      reference group, the median optic-disc area was significantly smaller (p = 0.013)
      in the children with hydrocephalus. There was no corresponding difference in cup
      area, so the rim area was significantly smaller in the hydrocephalic children (p
      = 0.002). Children with hydrocephalus had an abnormal retinal vascular pattern,
      with significantly straighter retinal arteries and fewer central vessel branching
      points compared with controls (p<0.001 and p<0.001, respectively). CONCLUSION:
      Hydrocephalus is associated with subnormal optic disc and rim areas and an
      abnormal vascular pattern, indicating a pre/perinatal disturbance of the
      development of these structures. A promising finding is that the frequency of
      optic atrophy in the present study was lower than previously reported, most
      likely reflecting improved perinatal care and better regulation of the
      intracranial pressure.

PMID- 19106150
TI  - Intraocular pressure control and fluctuation: the effect of treatment with
      selective laser trabeculoplasty.
AB  - AIMS: To evaluate the effect of selective laser trabeculoplasty (SLT) on
      intraocular pressure (IOP) control and diurnal tension curves of patients with
      open-angle glaucoma (OAG) and ocular hypertension (OHT), and to compare this
      effect with that of latanoprost. METHODS: Forty patients were randomised to
      receive either SLT or latanoprost. IOP control was evaluated by comparing
      pretreatment values with post-treatment measurements on day 3, week 1, month 1
      and 4-6 months; success was defined as 20% decrease in IOP. Tension curves were
      plotted prior to treatment and 4-6 months afterwards; success was 50% reduction
      in fluctuation. RESULTS: SLT decreased pressure by 4.7 mm Hg on average (95% CI
      3.6 to 5.7 mm Hg; p<0.01). The reduction was similar for latanoprost at all
      follow-ups except month 1; 75% of SLT patients and 73% of latanoprost patients
      achieved success in IOP control (p = 0.4). SLT significantly reduced IOP
      fluctuation, but latanoprost was more effective (3.6 mm Hg, 95% CI 3.2 to 3.9 mm
      Hg vs 2.5 mm Hg, 95% CI 2.2 to 2.9 mm Hg for SLT; p = 0.04). Success in
      fluctuation reduction was 50% for SLT and 83% for latanoprost (p = 0.045).
      CONCLUSIONS: Both SLT and latanoprost had a significant impact on IOP control and
      fluctuation. While latanoprost may be more likely to reduce IOP fluctuation, SLT
      has the benefit of being a one-time intervention not requiring ongoing patient
      compliance.

PMID- 19106151
TI  - Should patients with chronic obstructive pulmonary disease be prescribed a
      resistance-training programme?

PMID- 19106152
TI  - The epidemiology of ankle injuries occurring in English Football Association
      academies.
AB  - OBJECTIVE: To ascertain the epidemiology of ankle injuries in elite youth
      football. DESIGN: Retrospective analysis of prospectively collected injury data
      from English Football Association (FA) academies. SETTING: Forty-one FA football
      academies, between 1998 and 2006. PARTICIPANTS: For the complete seasons studied,
      a total of 14 776 players was registered from U9 to the U16 age category, a mean
      of 2463 players per year. All ankle injuries of sufficient severity to miss 48 h
      or more of training were studied, 2563 injuries in total. MAIN OUTCOME MEASURE:
      The incidence and burden of ankle injuries in this population and factors
      associated with injury. RESULTS: There was a mean incidence of one ankle injury
      per player per year, and a mean of 20 training days and two matches were missed
      per ankle injury. Increased injury rates were seen in older players, in
      competition and later in each half of match time. Peaks in injury were observed
      early in the season and after the winter break. In competition, more injuries
      were associated with a contact situation than in training. Eighty-eight injuries
      (3.4%) required a lay-off of 3 months or more and in 18 (0.7%) cases the player
      failed to return to training. In total, 52 290 training days and 5182 match
      appearances were lost through ankle injury. The majority of injuries were
      sprains, but more severe injuries occurred accounted for 3.9% of the total.
      CONCLUSIONS: Ankle injuries are common in young football players and are often
      severe, with prolonged loss of training time. This has potential far-reaching
      implications, both on and off the field.

PMID- 19106153
TI  - Are drug-eluting stents safe in the long term?

PMID- 19106154
TI  - Incremental change, rather than wholesale reform, expected from new US president
      Barack Obama.

PMID- 19106155
TI  - Remote ischemic preconditioning stimulus does not reduce microvascular resistance
      or improve myocardial blood flow in patients undergoing elective percutaneous
      coronary intervention.
AB  - INTRODUCTION: Remote ischemic preconditioning (RIPC) may limit myocardial
      infarction by improving microvascular function and maintaining myocardial blood
      flow. We hypothesized that a RIPC stimulus would reduce coronary microvascular
      resistance and improve coronary blood flow during elective percutaneous coronary
      intervention (PCI). METHOD: We prospectively recruited 54 patients with multi
      vessel disease (MVD = 32) or single vessel disease awaiting elective PCI.
      Patients with MVD had non-target vessel (NTV) index of micro-circulatory
      resistance (IMR) determined, before and after target vessel (TV) PCI (cardiac
      RIPC). The effect of arm RIPC on serial microvascular resistance (R(p)) was
      assessed in patients with single vessel disease. RESULTS: TV balloon occlusion
      did not alter the NTV IMR: 16.5 (12.4) baseline vs. 17.6 (11.6) post cardiac
      RIPC, P = 0.65 or hyperaemic transit time. Arm RIPC did not alter R( p) in
      patients with single vessel disease: Rp, mmHg.cm(-1).s( -1): 3.5 (1.9) baseline
      vs. 4.1 (3.0) post arm RIPC, P = 0.19 and coronary flow velocity remained
      constant. CONCLUSION: RIPC stimuli during elective PCI do not affect coronary
      microvascular resistance or coronary flow in humans.

PMID- 19106156
TI  - Serum sodium as a risk factor for in-hospital mortality in acute unselected
      general medical patients.
AB  - BACKGROUND: Serum sodium has been shown to predict mortality in heart and liver
      failure. AIM: To determine whether serum sodium independently predicts in
      hospital mortality during any emergency medical admission. DESIGN: An analysis
      was performed of all emergency medical patients admitted to St James's Hospital
      (SJH), Dublin between 1 January 2002 and 31 December 2006, using the hospital
      inpatient enquiry (HIPE) system, linked to the patient administration system and
      laboratory datasets. Hospital mortality was obtained from a database of 20 deaths
      occurring during the same period under physicians participating in the 'on call'
      roster. METHODS: The serum sodium was determined at admission in all cases where
      it was deemed clinically necessary. Logistic regression was used to calculate
      crude and 25 adjusted odds ratios (ORs). Factors adjusted for included age,
      illness severity score (Modified Apache II score), major disease category, ICU
      stay, year effect, blood transfusion, gender and sepsis. RESULTS: A total of 14
      239 patients (47.5% male) were included in the analysis. Mortality had a U-shaped
      distribution and was highest in patients whose sodium level was <125 or >140
      mmol/l. The unadjusted OR of death within 30 days of admission was 3.36 (95% CI
      2.59-4.36) and 4.07 (95% CI 2.95-5.63) with sodium level <125 and >140 mmol/l,
      respectively. Adjustment for all of the factors above reduced the mortality odds
      in all hyponatraemia groups but all remained significant predictors of mortality.
      After adjustment for illness severity score the OR ratio for death in the >140
      mmol/l group fell to 1.41 (95% CI 0.97-2.07). DISCUSSION: The serum sodium is a
      powerful initial marker of likely mortality in unselected general medical
      patients. The increased death rate in hyponatraemic patients is independent of
      other clinical variables, whereas mortality in the hypernatraemic group is
      primarily a factor of illness severity.

PMID- 19106157
TI  - Structural divergence of cysteine-rich secretory proteins in snake venoms.
AB  - Cysteine-rich secretory proteins (CRISPs) are expressed in spermatocytes and
      granules of neutrophils in mammals, and are associated with sperm maturation and
      host defense. Related proteins have recently been recovered in snake venoms, and
      some of the snake venom-derived CRISPs exhibit ion channel blocking activity.
      Here we isolated and identified two novel CRISPs (kaouthin-1 and kaouthin-2) from
      the venom of Naja kaouthia (Elapidae), and cloned the encoding cDNAs. Kaouthin-1
      and kaouthin-2 were classified into two broad sister groups of Elapidae, the
      Asian species and the marine/Australian species, respectively. Sequence
      comparisons reveal that the high-frequency variable regions among snake venom
      CRISPs define a continuous line on the molecular surface of the N-terminal
      pathogenesis-related protein-1 (PR-1) domain and the C-terminal cysteine-rich
      domain (CRD). Snake venom proteins generally display efficient molecular
      diversity around functionally key regions, suggesting that the PR-1 domain of
      CRISPs is important for the recognition of target molecules.

PMID- 19106158
TI  - Blockage by SP600125 of Fcepsilon receptor-induced degranulation and cytokine
      gene expression in mast cells is mediated through inhibition of
      phosphatidylinositol 3-kinase signalling pathway.
AB  - SP600125 is used as a specific inhibitor of c-Jun N-terminal kinase (JNK). We
      initially aimed to examine physiological roles of JNK in mast cells that play a
      central role in inflammatory and immediate allergic responses. We found that Fc
      receptor for IgE (FcepsilonRI)-induced degranulation (serotonin release) and
      cytokine gene expression [interleukin (IL)-6, tumour necrosis factor-alpha and IL
      13] in bone marrow-derived mast cells, were almost completely inhibited by
      SP600125. However, the time course of FcepsilonRI-induced JNK activation did not
      correlate with that of serotonin release. Furthermore, FcepsilonRI-induced
      degranulation and cytokine gene expression were not impaired in a JNK activator,
      MKK7-deficient mast cells, in which JNK activation was lost. These results
      indicate that the inhibitory effects by SP600125 are not due to impaired JNK
      activation. Instead, we found that SP600125 markedly inhibited the FcepsilonRI
      induced activation of phosphatidylinositol 3-kinase (PI3K) and Akt, the same as a
      PI3K inhibitor, wortmannin. Finally, we found that SP600125 specifically inhibits
      delta form of p110 catalytic subunit (p110delta) of PI3K. Thus, SP600125 exerts
      its influence on mast cell functions by inhibiting the kinase activity of PI3K,
      but not JNK.

PMID- 19106159
TI  - Beta-catenin induces beta-TrCP-mediated PER2 degradation altering circadian clock
      gene expression in intestinal mucosa of ApcMin/+ mice.
AB  - Proliferation of intestinal epithelial cells is rhythmic throughout the day. This
      temporal organization occurs through the interaction between the endogenous
      peripheral circadian clock and pathways controlling cell cycle progression. Per2,
      a core clock gene with tumour suppresser function, is critical to clock function
      and to the regulation of cellular proliferation. Circadian disruption, which
      increases colon cancer incidence, may do so by deregulating clock controlled
      epithelial cell proliferation. Increased expression of beta-catenin is a
      contributing cause of most familial and spontaneous human colon cancer and the
      cause of multiple intestinal neoplasia of the Apc(Min/+) mouse. Here we report
      that increased beta-catenin destabilizes PER2 clock protein by inducing beta
      TrCP, an F-box protein of SCF ubiquitin E3 ligase. In the intestinal mucosa of
      the Apc(Min/)(+) mouse, the decrease in PER2 protein levels is associated with
      altered circadian rhythms of clock genes, Per1 and Per2, and clock controlled
      genes, Dbp and Wee1. These findings suggest that disruption of the peripheral
      intestinal circadian clock may be intimately involved in beta-catenin induced
      intestinal epithelial neoplastic transformation in both mouse and man.

PMID- 19106160
TI  - Quantitative biological mass spectrometry. Editorial.

PMID- 19106161
TI  - Quantitative matrix-assisted laser desorption/ionization mass spectrometry.
AB  - This review summarizes the essential characteristics of matrix-assisted laser
      desorption/ionization (MALDI) time-of-flight mass spectrometry (TOF MS),
      especially as they relate to its applications in quantitative analysis.
      Approaches to quantification by MALDI-TOF MS are presented and published
      applications are critically reviewed.

PMID- 19106162
TI  - Stable isotopic labeling of proteins for quantitative proteomic applications.
AB  - Straightforward methods for the introduction of stable isotopes into proteins
      with subsequent isolation and purification of the proteins will greatly aid the
      field of quantitative proteomics. Proteins containing amino acids with one or
      more of the stable isotopes of deuterium, 13C, 15N or 18O can be used as internal
      standards by addition at an early stage of analysis of a complex protein sample
      and subsequent measurement using mass spectrometry. There are two approaches for
      introducing a stable isotope into a protein without chemically modifying that
      protein, metabolic labeling using whole cells grown in culture, or cell-free
      labeling using a lysate of either Escherichia coli or wheat germ. Each approach
      has its advantages and disadvantages which will be discussed. Particular
      attention will be paid to the cell-free method using an E. coli lysate.

PMID- 19106163
TI  - Fatigue: an overlooked determinant of physical function in scleroderma.
AB  - OBJECTIVES: To examine the frequency and correlates of fatigue and its impact on
      physical and social functioning in patients with scleroderma, and to investigate
      whether fatigue mediates an association between pain and physical function.
      METHODS: One hundred and seven scleroderma patients attending an academic
      scleroderma specialty centre completed measures of fatigue, sleep, pain,
      depressive symptoms, and physical and social functioning. Patients had received a
      comprehensive clinical assessment with a diagnosis of limited or diffuse
      scleroderma from their attending rheumatologist. RESULTS: In this sample of
      scleroderma patients, 76% reported experiencing fatigue and 61% of these patients
      reported fatigue as one of their three most distressing symptoms. Patients
      endorsing greater pain had higher levels of self-reported fatigue, as did those
      reporting greater depression and poorer functioning. Multiple regression analyses
      indicated that global fatigue was a significant cross-sectional correlate of
      physical, but not social, functioning after controlling for depressive symptoms,
      level of education, poor sleep quality and disease subtype. However, global
      fatigue did not predict physical function when pain was included in the analyses.
      CONCLUSIONS: Our findings indicate that fatigue is common in scleroderma and that
      pain and fatigue are significant determinants of physical functioning for
      patients with limited and diffuse disease subtypes. Future research should
      investigate whether effective pain treatments reduce symptoms of fatigue, as well
      as identify other possible causes of fatigue in order to improve quality of life
      for scleroderma patients.

PMID- 19106164
TI  - Dose escalation of infliximab therapy in arthritis patients is related to
      diagnosis and concomitant methotrexate treatment: observational results from the
      South Swedish Arthritis Treatment Group register.
AB  - OBJECTIVE: To study frequency of dose escalation in infliximab-treated patients
      and to identify possible predictors thereof. METHODS: Patients with chronic
      arthritis initiating their first course of anti-TNF treatment with infliximab at
      Lund University Hospital were included in a structured clinical follow-up
      protocol. Information on diagnosis, drug dosage, disease duration, previous and
      ongoing DMARDs, treatment start and cessation were prospectively collected during
      the period March 1999 through February 2007. All patients were started on a dose
      of 3 mg/kg at time 0, week 2, week 6 and then every eighth week independent of
      diagnosis and were followed for a period of 2 yrs. RESULTS: A total of 206
      patients were included in the study. Thirty-two of the patients had PsA, 25 had
      AS and 149 patients had RA. A minor dose escalation, defined as less than
      doubling of the dosage, was observed for 53, 48 and 42% of the patients with PsA,
      AS and RA, respectively. The corresponding values for major dose escalation was
      observed for 19, 8 and 15% of the patients, respectively. Regression analysis
      showed that patients with a diagnosis of PsA (P = 0.03), longer follow-up period
      (P < 0.01), and lack of concomitant MTX treatment (P = 0.03) were significantly
      associated with risk of dose escalation. CONCLUSION: Dose escalations were
      performed in 59% of all infliximab-treated patients during the first 2 yrs of
      treatment. Our data suggest that PsA patients might require higher dosages than
      RA and AS patients.

PMID- 19106165
TI  - Can patients help with long-term total knee arthroplasty surveillance? Comparison
      of the American Knee Society Score self-report and surgeon assessment.
AB  - OBJECTIVES: To compare patient self-report of knee flexion, extension, range of
      motion (ROM) and American Knee Society (AKS) Pain, Knee and Functional scores
      with a clinician assessment. METHODS: A total of 239 consecutive total knee
      arthroplasty (TKA) patients (290 knees) were mailed surveys with an AKS
      questionnaire and lateral knee photographs that showed knee ROM in 10 degrees
      increments to compare their operated knee(s) ROM. Patients were subsequently seen
      in clinic and their ROM, AKS Pain, Knee and Functional scores were measured.
      Patient- and physician-reported measures were compared using independent sample t
      test and correlated using Spearman's correlation coefficient. A priori rules for
      comparisons were based on previously published reports. RESULTS: A total of 286
      knees had both survey and clinic data available and constituted the analytic set.
      Patient-reported and physician-assessed extension, flexion and ROM were: 3 +/-
      4.8 degrees vs 1.4 +/- 4.3 degrees (P < 0.001), 111.4 +/- 14.6 degrees vs 110 +/-
      12.8 degrees (P = 0.04) and 108.6 +/- 16.8 vs 108.6 +/- 14.3 degrees (P = 0.98).
      There was a moderate correlation between patient and physician assessments
      (extension = 0.31; flexion = 0.44; ROM = 0.42; P < or = 0.001 for all). Patient
      reported and physician-assessed AKS Pain, Knee and Functional scores were: 35.8
      +/- 15.6 vs 43.9 +/- 11.1 (P < 0.001), 79.8 +/- 20 vs 88.9 +/- 13.3 (P < 0.001)
      and 57.7 +/- 23.1 vs 65.7 +/- 26.4 (P < 0.001), respectively. Patient- and
      physician-assessed AKS Pain, Knee and Functional scores had moderate-high
      correlation (r = 0.49, 0.49 and 0.70; P < or = 0.001 for all). CONCLUSION: Long
      term surveillance of TKA patients may be possible using a self-report AKS, but
      the average 8- to 10-point difference between patient- and physician-reported AKS
      scores (patients reporting poorer scores) represents a substantial impact on this
      outcome instrument. Since patient-reported responses have clear value in global
      assessment, further evaluation with other validated outcome instruments is
      warranted.

PMID- 19106166
TI  - Pericardial effusions on anti-TNF therapy for rheumatoid arthritis--a drug side
      effect or uncontrolled systemic disease?

PMID- 19106168
TI  - Transforming growth factor-beta1 869T/C, but not interleukin-6 -174G/C,
      polymorphism associates with hypertension in rheumatoid arthritis.
AB  - OBJECTIVES: Part of the deleterious effects of systemic inflammation on the
      cardiovascular system of patients with RA may be exerted via increased propensity
      to hypertension. IL-6 and TGF-beta1 are important regulators of the inflammatory
      response. In some, but not all, studies, IL6 -174G/C (rs1800795) and TGFB1 869T/C
      (rs1982073) gene polymorphisms have been associated with hypertension in the
      general population. The present study addressed their potential association with
      hypertension in RA patients. METHODS: TGFB1 869T/C and IL6 -174G/C were
      identified in 400 RA patients and 422 local, non-RA controls using real-time PCR
      and melting curve analysis. Binary logistic and linear regression models were
      used to identify the independence of the effects of the polymorphisms on
      hypertension. RESULTS: Genotypic and allelic frequencies of the two polymorphisms
      were similar in RA and controls. Within the RA group, there was no significant
      association between IL6 -174G/C and hypertension, but TGF 869T-allele carriers
      had significantly increased prevalence of hypertension compared with CC
      homozygotes (70.2 vs 55.2%; P = 0.023). This association remained significant
      after adjustment for other hypertension risk factors and medication (odds ratio =
      1.96; 95% CI 1.02, 3.77; P = 0.044), and was more pronounced in patients with
      increased systemic inflammation. CONCLUSIONS: This study suggests an association
      of TGFB1 869T/C, but not of IL6 -174G/C, with hypertension in RA patients. If
      this finding is confirmed in prospective studies, this polymorphism could be used
      as a screening tool for RA patients with higher risk of developing hypertension
      and lead to increased surveillance and earlier treatment.

PMID- 19106169
TI  - Sustained response to tocilizumab, anti-interleukin-6 receptor antibody, in two
      patients with refractory relapsing polychondritis.

PMID- 19106170
TI  - Preclinical efficacy and safety of 1-deoxygalactonojirimycin in mice for Fabry
      disease.
AB  - Fabry disease is an inborn error of glycosphingolipid metabolism caused by
      deficiency of alpha-galactosidase A (alpha-Gal A) activity. It has been shown
      that protein misfolding is primarily responsible for the enzyme deficiency in a
      large proportion of mutations identified in Fabry patients with residual enzyme
      activity, and 1-deoxygalactonojirimycin (DGJ) can effectively increase the
      residual enzyme activity in cultured patient's cells. Herein, we demonstrate the
      preclinical efficacy and safety of DGJ in transgenic mice that express human
      mutant alpha-Gal A activity. alpha-Gal A activity in heart, kidney, spleen, and
      liver was increased dose- and time-dependently. The mutant alpha-Gal A was
      increased in cardiomyocytes and distal convoluted tubules of the transgenic mice
      in a null background after 2 weeks of DGJ treatment. Globotriaosylceramide
      storage was remarkably reduced in kidney of mice after a 4-week treatment at a
      dosage of approximately 3 mg/kg body weight/day. The half-life of DGJ was less
      than 1 day in all major issues and that of the enzyme synthesized during the DGJ
      treatment period was approximately 4 days. No abnormality of blood chemistry and
      pathological tissue damage was found in mice treated with DGJ at approximately 30
      mg/kg body weight/day for 9 weeks. Furthermore, no change was observed in
      appearance, growth, fertility, and life span in mice during a 2-year period of
      continuous administration of DGJ at the effective dosage. These preclinical
      results indicate that DGJ is effective in restoring mutant enzyme activity in
      tissues and reversing substrate storage in kidney and is well tolerated in mice.

PMID- 19106171
TI  - Cannabinoid agonists stimulate [3H]GABA release in the globus pallidus of the rat
      when G(i) protein-receptor coupling is restricted: role of dopamine D2 receptors.
AB  - The motor effects of cannabinoids in the globus pallidus appear to be caused by
      increases in interstitial GABA. To elucidate the mechanism of this response, we
      investigated the effect of the selective cannabinoid type 1 receptor (CB1)
      cannabinoid agonist arachidonyl-2-chloroethylamide (ACEA) on [(3)H]GABA release
      in slices of the rat globus pallidus. ACEA had two effects: concentrations
      between 10(-8) and 10(-6) M stimulated release, whereas higher concentrations
      (IC(50) approximately 10(-6) M) inhibited it. Another cannabinoid agonist, WIN
      55,212-2, also had bimodal effects on release. Studies of cAMP production
      indicate that under conditions of low G(i/o), availability the coupling of CB1
      receptors with G(i/o) proteins can be changed into CB1:G(s/olf) coupling;
      therefore, we determined the effects of conditions that limit G(i/o) availability
      on [(3)H]GABA release. Blockers of G(i/o) protein interactions, pertussis toxin
      and N-ethylmaleimide, transformed the inhibitory effects of ACEA on GABA release
      into stimulation. It also has been suggested that stimulation of D2 receptors can
      reduce G(i/o) availability. Blocking D2 receptors with sulpiride [(S)-5
      aminosulfonyl-N-[(1-ethyl-2-pyrrolidinyl)methyl]-2-methoxybenzamidersqb] or
      depleting dopamine with reserpine inhibited the ACEA-induced stimulation of
      release. Thus, the D2 dependence of stimulation is consistent with the proposal
      that D2 receptors reduce G(i/o) proteins available for binding to the CB1
      receptor. In summary, CB1 receptor activation has dual effects on GABA release in
      the globus pallidus. Low concentrations stimulate release through a process that
      depends on activation of dopamine D2 receptors that may limit G(i/o) protein
      availability. Higher concentrations of cannabinoid inhibit GABA release through
      mechanisms that are independent of D2 receptor activation.

PMID- 19106173
TI  - The expanding cardiovascular phenotype of Marfan syndrome.

PMID- 19106172
TI  - Cluster analysis and comparison of various chloroplast transcriptomes and genes
      in Arabidopsis thaliana.
AB  - Chloroplast RNA metabolism is integrated into wider gene regulatory networks. To
      explore how, we performed a chloroplast genome-wide expression analysis on
      numerous nuclear Arabidopsis mutants affected in diverse chloroplast functions
      and wild-type plants subjected to various stresses and conditions. On the basis
      of clustering analysis, plastid genes could be divided into two oppositely
      regulated clusters, largely congruent with known targets of nucleus- and plastid
      encoded RNA polymerases, respectively. Further eight sub-clusters contained co
      transcribed and functionally tightly associated genes. The chloroplast
      transcriptomes could also be classified into two major groups comprising mutants
      preferentially affected in general plastid gene expression and other chloroplast
      functions, respectively. Deviations from characteristic expression profiles of
      transcriptomes served to identify novel mutants impaired in accumulation and/or
      processing of specific plastid RNAs. Expression profiles were useful to
      distinguish albino mutants affected in plastid gene expression from those with
      defects in other plastid functions. Remarkably, biotic and abiotic stressors did
      not define transcriptionally determined clusters indicating that post
      transcriptional regulation of plastid gene expression becomes more important
      under changing environmental conditions. Overall, the identification of sets of
      co-regulated genes provides insights into the integration of plastid gene
      expression into common pathways that ensures a coordinated response.

PMID- 19106174
TI  - Rhesus macaque embryos derived from MI oocytes maturing after retrieval display
      high rates of chromosomal anomalies.
AB  - BACKGROUND: Rhesus macaque and human preimplantation embryos display similar
      rates of chromosomal abnormalities. The aim of this study was to determine
      whether embryos developing from MI oocytes that mature post-retrieval display
      more chromosomal anomalies than those embryos that are generated from oocytes
      that are at MII at the time of retrieval. METHODS: Rhesus macaque oocytes were
      obtained after hormonal ovarian stimulation. Immediately after retrieval, the
      oocytes were classified according to their maturational status. Following in
      vitro fertilization, Day 3 embryos with good morphology and development derived
      from oocytes maturing post-retrieval and those from oocytes that were mature at
      the time of retrieval were cytogenetically assessed using a five-color
      fluorescent in situ fluorescent hybridization assay developed for rhesus macaque
      chromosomes homologous to human chromosomes 13, 16, 18, X and Y. RESULTS:
      Blastomeres from 53 embryos were analyzed. Of the 27 embryos that developed from
      oocytes that were mature at collection, 18 embryos were chromosomally normal
      (66.7%), while from the 26 embryos that developed from oocytes that matured post
      retrieval, only 9 embryos were chromosomally normal (34.6%). CONCLUSIONS: These
      results indicate that embryos developing from oocytes maturing post-retrieval
      display high rates of chromosomal abnormalities and have therefore a reduced
      developmental competence. As a result, the clinical relevance of using immature
      oocytes that are retrieved after stimulated cycles in human IVF warrants further
      investigation.

PMID- 19106175
TI  - Change in gene expression of mouse embryonic stem cells derived from
      parthenogenetic activation.
AB  - BACKGROUND: We previously established parthenogenetic mouse embryonic stem cells
      (ESCs) and this study was subsequently conducted for elucidating the influence of
      oocyte parthenogenesis on gene expression profile of ESCs. METHODS: Gene
      expression of parthenogenetic ESC (pESC)-1 or pESC-2 was separately compared with
      that of two normally fertilized ESC (nfESC) lines (B6D2F1 and R1 strains), and
      quantification of mRNA expression was conducted for validating microarray data.
      RESULTS: In two sets of comparison, reaction of 11 347 and 15 454 gene probes
      were altered by parthenogenesis, while strain difference changed the expression
      of 15 750 and 14 944 probes. Level of correlation coefficient was higher in the
      comparisons between normal fertilization and parthenogenesis (0.974-0.985) than
      in the comparisons between strains of nfESCs (0.97-0.971). Overall, the
      expression of 3276-3329 genes was changed after parthenogenesis, and 88% (96/109)
      of major functional genes differentially (P < 0.01) expressed in one comparison
      set showed the same change in the other. When we monitored imprinted genes,
      expression of nine paternal and eight maternal genes were altered after
      parthenogenesis and 88% (14/16) of these was confirmed by mRNA quantification.
      CONCLUSIONS: The change in gene expression after parthenogenesis was similar to,
      or less than, the change induced by a strain difference under a certain genetic
      background. These results may suggest the clinical feasibility of parthenogenesis
      derived, pluripotent cells.

PMID- 19106176
TI  - Adjustment to infertility: the role of intrapersonal and interpersonal
      resources/vulnerabilities.
AB  - BACKGROUND: Great variability exists in the degree of adjustment to infertility,
      which in turn is known to influence wellbeing. The main objective of this study
      is to identify intrapersonal [neuroticism, adult attachment style (AAS),
      perceived internal control, meaning of parenthood and intrinsic religiosity] and
      interpersonal (social support and marital adjustment) associates of adjustment to
      infertility. METHOD: A cross-sectional analysis of 85 consecutive heterosexual
      women, attending three infertility clinics in northern India during July 2005
      March 2006, participated in the study. A range of scales were used to measure the
      intrapersonal and interpersonal attributes. The degree of adjustment to
      infertility was assessed using the Fertility Adjustment Scale. The data were
      analysed using multiple regression. RESULTS: The intrapersonal model (49.3%)
      explained a larger proportion of variance than did the interpersonal model
      (28.4%). Perception of children as necessary for marital completion, and the
      avoidance type of AAS was associated with poorer adjustment and constituted
      intrapersonal vulnerabilities. In contrast, intrinsic religiosity, sexual
      satisfaction and familial support were associated with better adjustment and were
      identified as helpful intrapersonal and interpersonal coping resources.
      CONCLUSIONS: The findings of the study highlight the merit of understanding intra
      and interpersonal attributes for achieving better wellbeing outcomes. These
      findings would also prove valuable for researchers and practioners involved in
      designing and implementing psychosocial interventions.

PMID- 19106177
TI  - Doses to patients in some routine diagnostic X-ray examinations in Iran: proposed
      the first Iranian diagnostic reference levels.
AB  - The national diagnostic reference levels (NDRLs) form an efficient, concise and
      powerful standard for optimising the radiation protection of a patient. With an
      aim to establish the first Iranian NDRLs, the nationwide survey of the frequency
      of medical X-ray examinations and entrance surface doses received by the patients
      during the most typical X-ray examinations has been performed. Seven most common
      X-ray examinations in 14 projections were included in the list of procedures
      under consideration. Hospitals of different sizes and levels using different X
      ray machines were represented in the survey. The standard thermoluminescence
      dosimeters were applied to measure entrance surface dose (ESD). A total of 1601
      patients were included in this study. The data were analysed statistically, and
      the minimum, median, mean, maximum, first and third quartile values of ESDs are
      reported. Finally, the proposed Iranian DRLs are compared with the international
      reference dose values reported by the European Commission, the International
      Atomic Energy Agency and the National Radiological Protection Board.

PMID- 19106178
TI  - A study on patients' radiation doses from interventional cardiac procedures in
      Tabriz, Iran.
AB  - Interventional cardiac procedures produce a large amount of X-ray exposures to
      the patients in comparison with other conventional X-ray imaging procedures. In
      the current study, the exposure parameters of 580 patients referred to a cardiac
      angiography department were recorded. The mean values of total kerma-area product
      (KAP) were 18.6 Gy cm2 for coronary angiography (CA) and 55 Gy cm2 for
      percutaneous transluminal coronary angioplasty (PTCA). The mean fluoroscopy time
      was 3.2 and 11.6 min, respectively, for CA and PTCA. The patients' exposure
      parameters during electrophysiological studies were 15.5 min for mean fluoroscopy
      time and 33.9 Gy cm2 for total KAP. For paediatrics, the mean fluoroscopy time of
      5.4 min and total KAP of 2 Gy cm2 were recorded. Comparing the proposed reference
      values, the authors think that the exposure level of patients in their department
      is at an acceptable level.

PMID- 19106180
TI  - Rapid loss of genetic variation in a founding population of Primula elatior
      (Primulaceae) after colonization.
AB  - BACKGROUND AND AIMS: Land-use changes and associated extinction/colonization
      dynamics can have a large impact on population genetic diversity of plant
      species. The aim of this study was to investigate genetic diversity in a founding
      population of the self-incompatible forest herb Primula elatior and to elucidate
      the processes that affect genetic diversity shortly after colonization. METHODS:
      AFLP markers were used to analyse genetic diversity across three age classes and
      spatial genetic structure within a founding population of P. elatior in a
      recently established stand in central Belgium. Parentage analyses were used to
      assess the amount of gene flow from outside the population and to investigate the
      contribution of mother plants to future generations. RESULTS: The genetic
      diversity of second and third generation plants was significantly reduced
      compared with that of first generation plants. Significant spatial genetic
      structure was observed. Parentage analyses showed that < 20 % of the youngest
      individuals originated from parents outside the study population and that > 50 %
      of first and second generation plants did not contribute to seedling recruitment.
      CONCLUSIONS: These results suggest that a small effective population size and
      genetic drift can lead to rapid decline of genetic diversity of offspring in
      founding populations shortly after colonization. This multigenerational study
      also highlights that considerable amounts of gene flow seem to be required to
      counterbalance genetic drift and to sustain high levels of genetic diversity
      after colonization in recently established stands.

PMID- 19106179
TI  - Evaluating the microtubule cytoskeleton and its interacting proteins in monocots
      by mining the rice genome.
AB  - BACKGROUND: Microtubules (MTs) are assembled by heterodimers of alpha- and beta
      tubulins, which provide tracks for directional transport and frameworks for the
      spindle apparatus and the phragmoplast. MT nucleation and dynamics are regulated
      by components such as the gamma-tubulin complex which are conserved among
      eukaryotes, and other components which are unique to plants. Following remarkable
      progress made in the model plant Arabidopsis thaliana toward revealing key
      components regulating MT activities, the completed rice (Oryza sativa) genome has
      prompted a survey of the MT cytoskeleton in this important crop as a model for
      monocots. SCOPE: The rice genome contains three alpha-tubulin genes, eight beta
      tubulin genes and a single gamma-tubulin gene. A functional gamma-tubulin ring
      complex is expected to form in rice as genes encoding all components of the
      complex are present. Among proteins that interact with MTs, compared with A.
      thaliana, rice has more genes encoding some members such as the MAP65/Ase1p/PRC1
      family, but fewer for the motor kinesins, the end-binding protein EB1 and the
      mitotic kinase Aurora. Although most known MT-interacting factors have apparent
      orthologues in rice, no orthologues of arabidopsis RIC1 and MAP18 have been
      identified in rice. Among all proteins surveyed here, only a few have had their
      functions characterized by genetic means in rice. Elucidating functions of
      proteins of the rice MT cytoskeleton, aided by recent technical advances made in
      this model monocot, will greatly advance our knowledge of how monocots employ
      their MTs to regulate their growth and form.

PMID- 19106181
TI  - Induction of caspase- and reactive oxygen species-independent phosphatidylserine
      externalization in primary human neutrophils: role in macrophage recognition and
      engulfment.
AB  - Macrophage recognition and disposal of neutrophils are important steps in the
      resolution of inflammation. Externalization of phosphatidylserine (PS) on the
      cell surface serves as a common recognition signal for macrophages and is
      associated with the apoptosis program in neutrophils. Here, we report that
      macrophage-differentiated PLB-985 cells induce rapid, caspase-independent PS
      externalization in human neutrophils. A similar degree of PS externalization was
      seen when neutrophils were cocultured with gp91(phox)-deficient PLB-985
      macrophages, thus demonstrating that macrophage-induced PS externalization was
      NADPH oxidase-independent. Macrophage-induced PS externalization required cell-to
      cell contact and kinase activation and was shown to correlate with neutrophil
      degranulation. Of note, the degree of engulfment of such PS-positive neutrophils
      by activated human monocyte-derived macrophages was considerably lower than for
      neutrophils undergoing constitutive apoptosis, indicating that PS externalization
      alone is not sufficient for macrophage disposal of neutrophils. However, addition
      of recombinant milk fat globule epidermal growth factor 8, a PS-binding protein,
      restored engulfment of the macrophage-cocultured target cells. Finally,
      neutrophils undergoing spontaneous apoptosis but not macrophage-cocultured
      neutrophils displayed surface expression and release of annexin I, and the
      addition of N-t-Boc-Phe-D-Leu-Phe-D-Leu-Phe (Boc1), a formyl peptide
      receptor/lipoxin receptor antagonist, suppressed clearance of apoptotic
      neutrophils. Conditioned medium from apoptotic neutrophils also promoted the
      engulfment of macrophage-cocultured neutrophils, and Boc1 blocked this process.
      Taken together, these studies highlight a novel pathway of PS externalization in
      primary human neutrophils and also provide evidence for an auxiliary function of
      annexin I in macrophage clearance of neutrophils.

PMID- 19106182
TI  - Isolation stress for 30 days alters hepatic gene expression profiles, especially
      with reference to lipid metabolism in mice.
AB  - To elucidate the physiological responses to a social stressor, we exposed mice to
      an isolation stress and analyzed their hepatic gene expression profiles using a
      DNA microarray. Male BALB/c mice were exposed to isolation stress for 30 days,
      and then hepatic RNA was sampled and subjected to DNA microarray analysis. The
      isolation stress altered the expression of 420 genes (after considering the false
      discovery rate). Gene Ontology analysis of these differentially expressed genes
      indicated that the stress remarkably downregulated the lipid metabolism-related
      pathway through peroxisome proliferator-activated receptor-alpha, while the lipid
      biosynthesis pathway controlled by sterol regulatory element binding factor 1,
      Golgi vesicle transport, and secretory pathway-related genes were significantly
      upregulated. These results suggest that isolation for 30 days with a mild and
      consecutive social stress regulates the systems for lipid metabolism and also
      causes endoplasmic reticulum stress in mouse liver.

PMID- 19106183
TI  - Role of p53 in mitochondrial biogenesis and apoptosis in skeletal muscle.
AB  - p53 is a tumor suppressor protein that also plays a role in regulating aerobic
      metabolism. Since skeletal muscle is a major source of whole body aerobic
      respiration, it is important to delineate the effects of p53 on muscle
      metabolism. In p53 knockout (KO) mice, we observed diminished mitochondrial
      content in mixed muscle and lowered peroxisome proliferator-activated receptor
      gamma (PPARgamma) coactivator (PGC)-1alpha protein levels in gastrocnemius
      muscle. In intermyofibrillar (IMF) mitochondria, lack of p53 was associated with
      reduced respiration and elevated reactive oxygen species production. Permeability
      transition pore kinetics remained unchanged; however, IMF mitochondrial
      cytochrome c release was reduced and DNA fragmentation was lowered, illustrating
      a resistance to mitochondrially driven apoptosis in muscle of KO mice. p53-null
      animals displayed similar muscle strength but greater fatigability and less
      locomotory endurance than wild-type (WT) animals. Surprisingly, the adaptive
      responses in mitochondrial content to running were similar in WT and KO mice.
      Thus p53 may be important, but not necessary, for exercise-induced mitochondrial
      biogenesis. In WT animals, acute muscle contractions induced the phosphorylation
      of p53 in concert with increased activation of upstream kinases AMP-activated
      protein kinase and p38, indicating a pathway through which p53 may initiate
      mitochondrial biogenesis in response to contractile activity. These data
      illustrate a novel role for p53 in maintaining mitochondrial biogenesis,
      apoptosis, and performance in skeletal muscle.

PMID- 19106184
TI  - Analysis of the hibernation cycle using LC-MS-based metabolomics in ground
      squirrel liver.
AB  - A hallmark of hibernation in mammals is metabolic flexibility, which is typified
      by reversible bouts of metabolic depression (torpor) and the seasonal shift from
      predominantly carbohydrate to lipid metabolism from summer to winter. To provide
      new insight into the control and consequences of hibernation, we used LC/MS-based
      metabolomics to measure differences in small molecules in ground squirrel liver
      in five activity states: summer, entering torpor, late torpor, arousing from
      torpor, and interbout arousal. There were significant alterations both seasonally
      and within torpor-arousal cycles in enzyme cofactor metabolism, amino acid
      catabolism, and purine and pyrimidine metabolism, with observed metabolites
      reduced during torpor and increased upon arousal. Multiple lipids also changed,
      including 1-oleoyllysophosphatidylcholine, cholesterol sulfate, and sphingosine,
      which tended to be lowest during torpor, and hexadecanedioic acid, which
      accumulated during a torpor bout. The results reveal the dramatic alterations
      that occur in several classes of metabolites, highlighting the value of
      metabolomic analyses in deciphering the hibernation phenotype.

PMID- 19106185
TI  - National Academy of Clinical Biochemistry Laboratory Medicine Practice
      guidelines: emerging biomarkers for primary prevention of cardiovascular disease.
AB  - BACKGROUND: Heart disease and stroke continue to be the leading causes of death
      in the US. As a result, investigators continue to look for new and emerging
      biomarkers of disease risk. Because many of these emerging biomarkers are not as
      well documented as those of conventional lipid and lipoprotein risk factors,
      their value in clinical practice needs to be critically appraised and appropriate
      guidelines developed for their proposed use. CONTENT: The National Academy of
      Clinical Biochemistry (NACB) convened a multidisciplinary expert panel to develop
      laboratory medicine practice guidelines for a selected subset of these emerging
      risk factors as applied in a primary prevention setting of heart disease and
      stroke. The NACB expert panel selected lipoprotein subclasses and particle
      concentration, lipoprotein(a), apolipoproteins A-I and B, high sensitivity C
      reactive protein (hsCRP), fibrinogen, white blood cell count, homocysteine, B
      type natriuretic peptide (BNP), N-terminal proBNP (NT-proBNP), and markers of
      renal function as biomarkers that fell within the scope of these guidelines.
      CONCLUSIONS: Based on a thorough review of the published literature, only hsCRP
      met all of the stated criteria required for acceptance as a biomarker for risk
      assessment in primary prevention.

PMID- 19106186
TI  - A patient with primary biliary cirrhosis and elevated LDL cholesterol.

PMID- 19106188
TI  - Simple photometric assay of dopamine-beta-hydroxylase activity in human blood:
      useful in clinical chemistry.

PMID- 19106189
TI  - Response of bone turnover biochemical markers to extracorporeal shock wave
      therapy in the management of long-bone nonunions.

PMID- 19106190
TI  - Specificity of a high-sensitivity cardiac troponin I assay using single-molecule
      counting technology.

PMID- 19106193
TI  - Glucose metabolism as a target of histone deacetylase inhibitors.
AB  - The therapeutic efficacy of histone deacetylase inhibitors (HDACI) is generally
      attributed to their ability to alter gene expression secondary to their effects
      on the acetylation status of transcription factors and histones. However, because
      HDACIs exhibit similar transcriptional effects in most cells, the molecular basis
      for their therapeutic selectivity toward malignant cells is largely unknown. In
      this study, we report that HDACI, of distinct chemotypes, quantitatively inhibit
      glucose transporter 1 (GLUT1)-mediated glucose transport into multiple myeloma
      cells through both down-regulation of GLUT1 and inhibition of hexokinase 1 (HXK1)
      enzymatic activity. Unexpectedly, however, this inhibition of glucose utilization
      is accompanied by an increase in amino acid catabolism with no increase in fatty
      acid oxidation. Our findings suggest that an HDACI-induced change in carbon
      source preference could contribute to the therapeutic efficacy of these drugs by
      creating a pattern of fuel utilization that is incompatible with rapid tumor
      growth and survival. Furthermore, these results, which implicate glucose
      metabolism as a target of HDACI, suggest that caution should be exercised in
      attributing effects of this class of drug to primary alterations in gene
      transcription.

PMID- 19106194
TI  - Estrogen receptor beta functions through nongenomic mechanisms in lung cancer
      cells.
AB  - Recent studies have shown that estrogens promote the growth of lung cancer cells
      and may potentially be responsible for increased susceptibility to lung cancer in
      women. These observations raise the possibility of using antiestrogens in
      treating and preventing lung cancer. However, it is not clear how estrogen
      receptors (ERs) modulate the growth of non-small cell lung cancer (NSCLC) cells.
      Our Western blotting and real-time PCR analysis showed that NSCLC cells expressed
      ERbeta, but not ERalpha. In addition, ERbeta-specific ligands, but not ERalpha
      specific ligands, promoted the growth of lung cancer cells. Furthermore,
      knockdown of ERbeta by short hairpin RNA constructs resulted in loss of estrogen
      dependent growth of lung cancer cells. Interestingly, endogenous ERbeta failed to
      transcriptionally activate estrogen response element (ERE)-luciferase constructs
      in NSCLC cells, suggesting a lack of genomic function. Upon further
      investigation, ERbeta was found to be in the cytoplasm in all lung cancer cells
      and failed to translocate to the nucleus in the presence of estrogen, as observed
      by biochemical, ArrayScan, and confocal microscopy experiments. Nonetheless,
      estrogen caused rapid activation of cAMP, Akt, and MAPK signaling pathways in
      lung cancer cells. Immunohistochemical analysis of lung tumor biopsies showed
      strong ERbeta staining in the cytoplasm, whereas no staining was observed for
      ERalpha. In conclusion, our results suggest that that proliferative effects of
      estrogen in lung cancer cells is mediated primarily, if not exclusively, by the
      nongenomic action of ERbeta.

PMID- 19106195
TI  - Pharmacological manipulation of the RAR/RXR signaling pathway maintains the
      repopulating capacity of hematopoietic stem cells in culture.
AB  - The retinoid X receptor (RXR) contributes to the regulation of diverse biological
      pathways via its role as a heterodimeric partner of several nuclear receptors.
      However, RXR has no established role in the regulation of hematopoietic stem cell
      (HSC) fate. In this study, we sought to determine whether direct modulation of
      RXR signaling could impact human HSC self-renewal or differentiation. Treatment
      of human CD34(+)CD38(-)lin(-) cells with LG1506, a selective RXR modulator,
      inhibited the differentiation of HSCs in culture and maintained long-term
      repopulating HSCs in culture that were otherwise lost in response to cytokine
      treatment. Further studies revealed that LG1506 had a distinct mechanism of
      action in that it facilitated the recruitment of corepressors to the retinoic
      acid receptor (RAR)/RXR complex at target gene promoters, suggesting that this
      molecule was functioning as an inverse agonist in the context of this
      heterodimer. Interestingly, using combinatorial peptide phage display, we
      identified unique surfaces presented on RXR when occupied by LG1506 and
      demonstrated that other modulators that exhibited these properties functioned
      similarly at both a mechanistic and biological level. These data indicate that
      the RAR/RXR heterodimer is a critical regulator of human HSC differentiation, and
      pharmacological modulation of RXR signaling prevents the loss of human HSCs that
      otherwise occurs in short-term culture.

PMID- 19106196
TI  - Improved regional function after autologous bone marrow-derived stem cell
      transfer in patients with acute myocardial infarction: a randomized, double-blind
      strain rate imaging study.
AB  - AIMS: To investigate whether intracoronary transfer of bone marrow progenitor
      cells (BMPCs) early after reperfusion of an acute myocardial infarction improves
      regional myocardial function in a randomized double-blind, placebo-controlled
      strain rate imaging study. METHODS AND RESULTS: Regional myocardial deformation
      was measured using velocity-derived strain rate imaging in 67 STEMI patients
      randomized 1:1 to intracoronary infusion of BMPC (n = 33) or placebo (n = 34).
      Myocardial segments were grouped into infarct (n = 232), border (n = 250), and
      remote (n = 526) based on MRI-delayed enhancement and the perfusion territory of
      the infarct-related vessel. Four months after revascularization and progenitor
      cell/placebo transfer, regional myocardial deformation (rate) improved
      significantly more in the infarct segments of BMPC patients (treatment effect on
      end-systolic strain: -3.7 +/- 1.0%, P = 0.0003; peak-systolic strain rate: -0.20
      +/- 0.07 s(-1), P = 0.0035). These findings were confirmed by a significantly
      greater improvement of longitudinal mitral valve ring displacement in the infarct
      walls of BMPC patients (treatment effect: 0.93 mm, P = 0.034). CONCLUSION:
      Intracoronary infusion of BMPC early after reperfusion of a STEMI improves
      recuperation of regional myocardial function at 4 months' follow-up. Quantitative
      assessment of regional systolic function might be more sensitive than global LV
      ejection fraction for the evaluation of BMPC therapy after STEMI.

PMID- 19106197
TI  - Diagnostic accuracy of computed tomography coronary angiography and evaluation of
      stress-only single-photon emission computed tomography/computed tomography hybrid
      imaging: comparison of prospective electrocardiogram-triggering vs. retrospective
      gating.
AB  - AIMS: To determine diagnostic accuracy, effective radiation dose, and potential
      value of computed tomography coronary angiography (CTCA) for hybrid imaging with
      single-photon emission computed tomography (SPECT) comparing prospective
      electrocardiogram (ECG)-triggering vs. retrospective ECG-gating. METHODS AND
      RESULTS: Two hundred patients underwent standard myocardial stress/rest- SPECT
      perfusion imaging, which served as standard of reference. One hundred consecutive
      patients underwent 64-slice CTCA using prospective ECG-gating, and were compared
      with 100 patients who had previously undergone CTCA using retrospective ECG
      gating. For predicting ischaemia, CTCA with prospective ECG-triggering and a
      stenosis cut-off >50% had a per-vessel sensitivity, specificity, negative, and
      positive predictive value of 100, 84, 100, and 30%; respective values for CTCA
      with retrospective ECG-gating were similar (P = n.s.): 86, 83, 98, and 33%.
      Combining CTCA with stress-only SPECT revealed 100% clinical agreement with
      regard to perfusion defects, and provided additional information in half the
      patients on preclinical coronary findings. Effective radiation dose was 2.2 +/-
      0.7 mSv for CTCA with prospective ECG-triggering, and 19.7 +/- 4.2 mSv with
      retrospective ECG-gating (P < 0.001) (5.4 +/- 0.8 vs. 24.1 +/- 4.3 mSv for hybrid
      imaging). CONCLUSION: Prospective ECG-triggering for CTCA reduces radiation dose
      by almost 90% without affecting diagnostic performance. Combined imaging with
      stress-only SPECT is an attractive alternative to standard stress/rest-SPECT for
      evaluation of coronary artery disease, offering additional information on
      preclinical atherosclerosis.

PMID- 19106198
TI  - Contemporary management of octogenarians hospitalized for heart failure in
      Europe: Euro Heart Failure Survey II.
AB  - AIMS: International guidelines are frequently not implemented in the elderly
      population with heart failure (HF). This study determined the management of
      octogenarians with HF enrolled in Euro Heart Failure Survey II (EHFS II) (2004
      05). METHODS AND RESULTS: We compared the clinical profile, 12 month outcomes,
      and management modalities between 741 octogenarians (median age 83.7 years) and
      2836 younger patients (median age 68.4 years) hospitalized for
      acute/decompensated HF. Management modalities were also compared with those
      observed in EHFS I (2000-01). Female gender, new onset HF (de novo),
      hypertension, atrial fibrillation, co-morbidities, disabilities, and low quality
      of life were more common in the elderly (all P < 0.001). Mortality rates during
      hospital stay and during 12 months after discharge were increased in
      octogenarians (10.7 vs. 5.6% and 28.4 vs. 18.5%, P < 0.001). Underuse and
      underdosage of medications recommended for HF were observed in the elderly.
      However, a significant improvement was observed when compared with EHFS I both in
      the overall HF octogenarian population and in the subgroup with ejection fraction
      < or =45% for prescription rates of ACE-I/ARBs, beta-blockers, and aldosterone
      antagonists at discharge (82 vs. 71%; 56 vs. 29%; 54 vs. 18.5%, respectively, all
      P < 0.01), as well as for recommended combinations and dosage. Prescription rates
      remained stable for 12 months after discharge in survivors. CONCLUSION: Our study
      confirms that the contemporary management of very elderly patients with HF
      remains suboptimal but that the situation is improving.

PMID- 19106199
TI  - Catheter ablation procedures: role of nation-wide registries.

PMID- 19106200
TI  - Electroanatomic properties of pulmonary vein antral regions enclosed by
      encircling ablation lesions.
AB  - AIMS: Encircling ablation of the right and left pulmonary venous antra is
      commonly practiced. The importance to procedure outcome of electrical isolation
      of unablated myocardium enclosed by the encircling lesions is increasingly clear.
      The safe and effective achievement of isolation is dependent on a thorough
      comprehension of the 'electroanatomic' ablation substrate. We sought to improve
      comprehension of this substrate by examining relationships between anatomy and
      electrogram amplitude and timing after encircling ablation. METHODS AND RESULTS:
      After deployment of encircling antral ablation lesions, detailed,
      echocardiographically guided mapping of endocardial regions enclosed by the
      lesions was performed. Among patients in whom the encircling lesion did not
      produce electrical isolation of the enclosed region (143 of 199 left antra and 37
      of 198 right antra), separate electrograms generated by enclosed atrial
      myocardium (EM) and contiguous non-enclosed myocardium (NEM) were apparent at
      most mapped sites. Non-enclosed myocardium electrogram amplitudes demonstrated a
      spatial pattern which could be understood by considering contiguous atrial
      anatomy. Enclosed myocardium electrogram amplitudes demonstrated distinct spatial
      patterns that were more variable and not related to contiguous anatomy; they
      guided one or more additional ablation lesions within the enclosed region, which
      produced isolation. Among patients in whom the encircling lesion did produce
      isolation of the enclosed region, only NEM electrograms were consistently
      observed. CONCLUSION: The relationships between anatomy and electrogram amplitude
      and timing detailed herein may be helpful during the conduct of encircling
      ablation with a goal of isolation of EM.

PMID- 19106201
TI  - Posttraumatic stress disorder among Sri Lankan University students as a
      consequence of their exposure to family violence.
AB  - The article presents the results of a study on the association between exposure
      to family violence (i.e., witnessing interparental violence and experiencing
      parental violence) during childhood and adolescence and adult posttraumatic
      stress disorder (PTSD). The study was conducted among a self-selected convenience
      sample of 476 students from Sri Lanka, using a self-administered questionnaire.
      The findings indicate that the more participants witnessed interparental violence
      and the more they experienced parental violence, the more they exhibited PTSD
      symptoms. Moreover, the findings reveal that participants' exposure to family
      violence explains a significant amount of the variance in their PTSD over and
      above the variance that can be attributed to their sociodemographic
      characteristics (age, gender, number of siblings, and family's socioeconomic
      status) and to their perceptions of the environment and functioning of their
      families. The limitations of the study and recommendations for future research
      are discussed.

PMID- 19106202
TI  - The hormonal induction of cervical remodeling in the common marmoset monkey
      (Callithrix jacchus).
AB  - Controversy still exists regarding the involvement of relaxin (RLX) in cervical
      reorganization throughout parturition in the human, despite its well-known role
      in facilitating extensive extracellular matrix (ECM) remodeling in diverse
      organs. Therefore, the aim of the present study was to examine the influence of
      RLX and estrogen (E2) on the cervical tissue of the common marmoset monkey. Two
      experimental designs were used: 1) in vivo analysis of the intracervical diameter
      under locally applied RLX and 2) ovariectomized (ov) marmosets were treated
      systemically with either recombinant human (rh) RLX, E2 or rhRLX+E2 to examine
      their action on the cervix. In vivo-locally applied rhRLX induced a distinct and
      significant widening of the cervix (before: 4.8+/-1.1 mm versus after: 5.7+/-0.9
      mm in diameter; P<0.030, MV+/-S.E.M.). This widening effect was most pronounced
      in animals without previous pregnancies. In vitro investigation of cervical
      tissue showed significantly increased wet weights after all three hormone
      treatments (E2: 0.27+/-0.07 g, RLX: 0.25+/-0.04 g, E2+RLX: 0.30+/-0.11 g; all
      P<0.05; MV+/-S.E.M.) versus controls (0.10+/-0.04 g). Furthermore, morphological
      changes such as loosening of the connective tissue structure and decline in
      collagen content, an increase in the number of eosinophils, increased the
      expression of matrix metalloproteinases (MMP1) and MMP2, as well as gene and
      protein expression of the RLX receptor RXFP1 could be detected in the cervical
      tissue after all hormone treatments, compared with controls. In summary, RLX has
      a potent widening effect on the cervix of the common marmoset monkey. Although E2
      is not required for this RLX effect, a combined application of E2 and RLX induced
      the most prominent cervical ripening.

PMID- 19106203
TI  - Expression and in vitro regulation of pituitary adenylate cyclase-activating
      polypeptide (pacap38) and its type I receptor (pac1-r) in the gonads of tilapia
      (Oreochromis mossambicus).
AB  - Pituitary adenylate cyclase-activating polypeptide (PACAP), a pleiotropic
      neuropeptide, has diverse functions in mammals. However, studies of the
      expression and function of PACAP and its receptor in fish, particularly in the
      reproductive system, are still limited. In this report, semi-quantitative RT-PCR
      and immunohistochemical staining were performed to identify expression domains of
      commercially important tilapia (Oreochromis mossambicus). PACAP (tpacap(38)) and
      its type I receptor (tpac(1)-r). Transcripts were detected in the brain,
      gallbladder, gill, heart, intestine, kidney, muscles, pancreas, spleen, stomach,
      testes, and ovaries, but not in the liver. Expression of tpacap(38) and tpac(1)-r
      mRNA in brain tissue was significantly higher in both sexes compared with other
      tissues. Addition of exogenous ovine PACAP(38) (0.25-5 nM), cAMP analog
      (dibutyryl-cAMP, 0.25-1.5 mM) or forskolin (adenylate cyclase activator, 1-10
      microM) significantly upregulated tpacap(38) in the gonads via a dose- and time
      dependent fashion. This effect reached a maximal level at 2 h after induction,
      and then decreased with prolonged culture for up to 4 or 8 h. Additionally, the
      expression levels of tpac(1)-r were not significantly affected by ovine PACAP(38)
      or dibutyryl-cAMP in either sex. Forskolin had a slightly inductive effect and
      its function could be suppressed with the addition of protein kinase A (PKA)
      inhibitor, H89 (10 microM), indicating involvement of the cAMP-PKA signaling
      pathway in the regulation of tpacap(38). Expression of tpacap(38) and tpac(1)-r
      in the gonads of tilapia suggests that PACAP may mediate gonadotropin action via
      paracrine/autocrine mechanisms in this bony fish.

PMID- 19106204
TI  - Fundamental frequency variation with an electrolarynx improves speech
      understanding: a case study.
AB  - PURPOSE: This study examined the effect of fundamental frequency (F0) variation
      on the intelligibility of speech in an alaryngeal talker who used an
      electrolarynx (EL). METHOD: One experienced alaryngeal talker produced variable
      F0 and a constant F0 with his EL as he read sentences aloud. As a control, a
      group of sentences with variable F0 was flattened at a constant F0. Twenty
      listeners heard these sentences in background noise and wrote down what they
      heard. RESULTS: Speech understanding was on average 14% better with variable F0
      controlled by the talker than the sentences produced with a constant F0 and the
      control sentences resynthesized with flattened F0. CONCLUSIONS: Variable F0
      contributes to speech understanding in noise. Because speech produced by an EL is
      considered to have poorer intelligibility in relation to other alaryngeal
      methods, training alaryngeal talkers to use variable F0 may prove to be of
      significant benefit for communication for those who use electrolarynges.

PMID- 19106205
TI  - Feeding tube placement in patients with advanced dementia: the beliefs and
      practice patterns of speech-language pathologists.
AB  - PURPOSE: To describe the beliefs and practices of speech-language pathologists
      (SLPs) about the use of percutaneous endoscopic gastrostomy (PEG) among patients
      with advanced dementia and dysphagia. METHOD: A survey was mailed to a
      geographically stratified random sample of 1,050 medical SLPs. RESULTS: The
      response rate was 57%, and 326 surveys met inclusion criteria. Fifty-six percent
      of SLPs recommended PEG for a patient with advanced dementia and dysphagia.
      Contrary to the evidence, many respondents believed that PEG improves nutritional
      status and increases survival. Relatively few SLPs believed that PEG improved
      patients' functional status or quality of life. Patient factors (e.g., age or
      prognosis) were more often identified as influences on recommendations for PEG
      than were extrinsic factors (e.g., cost). Nearly 40% believed that PEG was the
      standard of care, while 15% believed it should be. Very few SLPs (11%) would want
      a PEG themselves. Perceived standard of care was significantly related to both
      geographic region and population density (p < .05), but self-reported practices
      were not. CONCLUSIONS: Discrepancies between SLPs' beliefs, the literature, and
      self-reported practices were observed. The findings suggest the need to connect
      the evidence base to clinical practice and to include SLPs in local and national
      discussions about end-of-life care protocols.

PMID- 19106206
TI  - Establishing a pedagogical framework for the multicultural course in
      communication sciences and disorders.
AB  - PURPOSE: To provide an overview of a model for teaching a foundational course in
      multicultural (MC) issues and to demonstrate how it can be modified for use in
      communication sciences and disorders (CSD) by integrating 3 primary dimensions of
      cultural competence: awareness, knowledge, and skills. METHOD: This tutorial
      begins by establishing the need for a basic foundational course in MC issues for
      CSD. Next, the authors describe a framework for MC instruction developed in the
      field of clinical counseling. Finally, the framework is modified and applied to
      the implementation of an MC course in CSD. CONCLUSION: The MC course in CSD can
      provide a useful foundation for facilitating the cultural competence of students
      in university training programs that have infused MC material across the American
      Speech-Language-Hearing Association's 9 content areas.

PMID- 19106207
TI  - The effect of aided language stimulation on vocabulary acquisition in children
      with little or no functional speech.
AB  - PURPOSE: To describe the nature and frequency of the aided language stimulation
      program and determine the effects of a 3-week-long aided language stimulation
      program on the vocabulary acquisition skills of children with little or no
      functional speech (LNFS). METHOD: Four children participated in this single
      subject, multiple-probe study across activities. The aided language stimulation
      program comprised 3 activities: arts and crafts, food preparation, and story time
      activity. Each activity was repeated over the duration of 5 subsequent sessions.
      Eight target vocabulary items were taught within each activity. The acquisition
      of all 24 target items was probed throughout the duration of the 3-week
      intervention period. RESULTS: The frequency and nature of the aided language
      stimulation provided met the criterion of being used 70% of the time and
      providing aided language stimulation with an 80:20 ratio of statements to
      questions. The results indicated that all 4 participants acquired the target
      vocabulary items. There were, however, variations in the rate of acquisition.
      CONCLUSIONS: This study explores the impact of aided language stimulation on
      vocabulary acquisition in children. The most important clinical implication of
      this study is that a 3-week intervention program in aided language stimulation
      was sufficient to facilitate the comprehension of at least 24 vocabulary items in
      4 children with LNFS.

PMID- 19106208
TI  - Feasibility and benefit of parent participation in a program emphasizing
      preschool child language development while homeless.
AB  - PURPOSE: This exploratory study examined the feasibility of homeless parents'
      participation in an intervention to increase use of facilitating language
      strategies during interactions with their preschool children while residing in
      family homeless shelters. This study also examined the intervention's impact on
      the parents' use of facilitating language strategies, regardless of parent
      performance on a single-word receptive vocabulary test. METHOD: Using a
      prospective, pretest/posttest comparison group design, 12 parents were randomly
      assigned to a 4-session experimental group training emphasizing use of
      facilitating language utterances with children following vocabulary testing. Four
      parents were randomly assigned to a control group intervention. RESULTS: It was
      feasible for parents to participate in the intervention. Before the intervention,
      individual experimental group parents with poor test performance demonstrated
      relatively high use of facilitating language utterances. After the intervention,
      the experimental group increased use of facilitating language utterances during
      interactions with their children. CONCLUSIONS: This exploratory study provides
      initial evidence that it is feasible for parents to participate in, and benefit
      from, a brief language-based group intervention while residing in family homeless
      shelters. Further study of language-based interventions for these at-risk
      families and of the possible impact of parent language functioning on
      intervention benefit is needed.

PMID- 19106209
TI  - Effects of robust vocabulary instruction and multicultural text on the
      development of word knowledge among African American children.
AB  - PURPOSE: To examine the effect of a systematic vocabulary instructional technique
      in African American 2nd-grade children with below average vocabulary skills. An
      additional goal was to examine the role of book type in the retention of novel
      vocabulary words. METHOD: Using an adapted alternating treatments design,
      storybooks were used as a source for contextualizing vocabulary words in the
      context of robust vocabulary training. Five children's productive definitions
      were used to assess developing word knowledge using a 4-stage continuum ranging
      from no knowledge to full concept knowledge. RESULTS: Superior word learning for
      instruction words in comparison with control words replicated across children
      provided evidence of behavior change that was attributable to robust vocabulary
      instruction. Gains in word learning were maintained 2 weeks following conclusion
      of the study. Use of storybooks that displayed sociocultural images and
      experiences that were similar to versus different from their own did not have a
      reliable effect on word learning among these African American children.
      CONCLUSIONS: The findings demonstrate the potential impact of robust vocabulary
      instruction for facilitating vocabulary development in children with below
      average vocabulary skills. Analysis of the results indicates that the use of the
      African American book was not a potent influence in facilitating retention of
      words.

PMID- 19106210
TI  - Syntactic development in adolescents with a history of language impairments: a
      follow-up investigation.
AB  - PURPOSE: Syntactic development in adolescents was examined using a spoken
      discourse task and standardized testing. The primary goal was to determine
      whether adolescents with a history of language impairments would differ from
      those with a history of typical language development (TLD). This is a companion
      study to one that examined these same adolescents 2 years earlier (M. A. Nippold,
      T. C. Mansfield, J. L. Billow, & J. B. Tomblin, 2008). METHOD: The participants
      were 15-year-old adolescents with a history of specific language impairment (SLI;
      n = 102), nonspecific language impairment (NLI; n = 77), or TLD (n = 247). A
      sample of spoken discourse was elicited using a Peer Conflict Resolution (PCR)
      task and analyzed for mean length of T-unit, clausal density, and subordinate
      clause use. In addition, 2 subtests from the Clinical Evaluation of Language
      Fundamentals, Third Edition (E. Semel, E. H. Wiig, & W. A. Secord, 1995),
      Concepts and Directions and Recalling Sentences, were administered. RESULTS: On
      the PCR task, the TLD group outperformed the SLI and NLI groups on mean length of
      T-unit, clausal density, and nominal clause use, and the TLD group outperformed
      the NLI group on relative clause use. On the standardized testing, the TLD group
      outperformed the SLI and NLI groups, and the SLI group outperformed the NLI
      group. Correlation coefficients calculated between the nonstandardized and
      standardized measures of syntax were statistically significant and positive.
      CONCLUSIONS: Speech-language pathologists may wish to employ the PCR task to
      examine syntactic development in adolescents as a supplement to standardized
      testing.

PMID- 19106211
TI  - Role of cytosolic NADP+-dependent isocitrate dehydrogenase in ischemia
      reperfusion injury in mouse kidney.
AB  - Cytosolic NADP+-dependent isocitrate dehydrogenase (IDPc) synthesizes reduced
      NADP (NADPH), which is an essential cofactor for the generation of reduced
      glutathione (GSH), the most abundant and important antioxidant in mammalian
      cells. We investigated the role of IDPc in kidney ischemia-reperfusion (I/R) in
      mice. The activity and expression of IDPc were highest in the cortex, modest in
      the outer medulla, and lowest in the inner medulla. NADPH levels were greatest in
      the cortex. IDPc expression in the S1 and S2 segments of proximal tubules was
      higher than in the S3 segment, which is much more susceptible to I/R. IDPc
      protein was also highly expressed in the mitochondrion-rich intercalated cells of
      the collecting duct. IDPc activity was 10- to 30-fold higher than the activity of
      glucose-6-phosphate dehydrogenase, another producer of cytosolic NADPH, in
      various kidney regions. This study identifies that IDPc may be the primary source
      of NADPH in the kidney. I/R significantly reduced IDPc expression and activity
      and NADPH production and increased the ratio of oxidized glutathione to total
      glutathione [GSSG/(GSH+GSSG)], resulting in kidney dysfunction, tubular cell
      damage, and lipid peroxidation. In LLC-PK(1) cells, upregulation of IDPc by IDPc
      gene transfer protected the cells against hydrogen peroxide, enhancing NADPH
      production, inhibiting the increase of GSSG/(GSH+GSSG), and reducing lipid
      peroxidation. IDPc downregulation by small interference RNA treatment presented
      results contrasting with the upregulation. In conclusion, these results
      demonstrate that IDPc is expressed differentially along tubules in patterns that
      may contribute to differences in susceptibility to injury, is a major enzyme in
      cytosolic NADPH generation in kidney, and is downregulated with I/R.

PMID- 19106212
TI  - Glomerular surface area is normalized in mice born with a nephron deficit: no
      role for AT1 receptors.
AB  - We examined whether deficits in glomerular capillary surface area associated with
      a congenital nephron deficit could be corrected by glomerular hypertrophy. Using
      unbiased stereological techniques, we examined the time course and mode of
      glomerular hypertrophy in mice lacking one allele for glial cell line-derived
      neurotrophic factor (GDNF). These GDNF heterozygous (Het) mice are born with
      approximately 30% less nephrons than wild-type (WT) littermates. An additional
      group of GDNF Het mice received the angiotensin type 1 (AT1)-receptor antagonist
      candesartan (Cand; 10 mg x kg(-1) x day(-1)) from 5 wk of age to determine the
      role of AT1 receptors in the compensatory hypertrophy. At 10 wk of age, the total
      volume of renal corpuscles, glomerular capillary surface area, and length of
      glomerular capillaries in the kidneys of GDNF Het mice were all markedly
      (approximately 45%) less than that of WT mice (P < 0.001). However, by 30 wk, and
      persisting at 60 wk of age, GDNF Het and WT mice did not significantly differ in
      any of these parameters. Furthermore, conscious 24-h mean arterial pressure (MAP)
      did not differ between GDNF Het and WT mice at any time point. MAP of GDNF Het
      Cand mice was 20-30 mmHg less than that of GDNF Het-vehicle mice at all three
      ages, but Cand treatment did not significantly alter glomerular capillary
      dimensions. In conclusion, we have demonstrated that the deficit in glomerular
      capillary surface area associated with a congenital nephron deficit can be
      corrected for in adulthood by an increase in the total length of glomerular
      capillaries. This process does not require AT1 receptor activation.

PMID- 19106213
TI  - Abnormal autoregulation and tubuloglomerular feedback in prediabetic and diabetic
      OLETF rats.
AB  - The mechanisms underlying the development and prevention of diabetic nephropathy
      are still not fully understood. In the present study in the Otsuka Long-Evans
      Tokushima Fatty (OLETF) model of type 2 diabetic rats, we investigated whether
      renal hemodynamic abnormalities exist and whether they precede the onset of
      diabetes. Using OLETF rats in both prediabetic and diabetic stages, we assessed
      autoregulatory responses of total renal blood flow (RBF) and of superficial (SBF)
      and deep renal cortical (DBF) blood flow to stepwise reductions of renal
      perfusion pressure (RPP) induced by a manual clamp on the abdominal aorta. During
      clamp-induced reductions of RPP by 10 or 20 mmHg, RBF fell significantly more in
      OLETF rats than in lean control [Long-Evans Tokushima Otsuka (LETO)] rats.
      Whereas SBF showed no significant changes in either OLETF rats or LETO rats
      during mild clamping, DBF decreased significantly more in OLETF rats than LETO
      rats. Reduced autoregulatory efficiency in OLETF rats was observed in both
      prediabetic and diabetic stages. Micropuncture studies showed that
      tubuloglomerular feedback (TGF) responses of stop flow pressure are reduced in
      prediabetic (-7.3 vs. -25.7%) as well as in diabetic OLETF rats compared with
      LETO control rats (-4.4 vs. -18.8%). Renal corticotomy was performed to measure
      glomerular capillary pressure (Pgc) directly. Pgc of deep cortical glomeruli was
      higher than superficial glomerular Pgc in both strains of rats, but the
      difference was especially pronounced in OLETF rats (deep 78 +/- 2 vs. superficial
      57 +/- 4 mmHg). This study demonstrates reduced autoregulatory adjustments and
      impaired TGF efficiency in prediabetic OLETF rats. Thus abnormal RBF regulation
      precedes the onset of diabetes and is especially pronounced in the deep cortical
      region.

PMID- 19106215
TI  - Subdiaphragmatic vagotomy prevents drinking-induced reduction in plasma
      corticosterone in water-restricted rats.
AB  - Dehydrated rats exhibit a rapid inhibition of the hypothalamic-pituitary-adrenal
      axis after rehydration. Drinking activates vagal afferents that project to
      neurons in the nucleus tractus solitarius (NTS). We hypothesized that when
      dehydrated rats drink, vagal afferents stimulate NTS neurons initiating
      inhibition of hypothalamic-pituitary-adrenal activity. Experiments assessed NTS
      activity by measuring Fos expression. Rats were water restricted for 1 or 6 d,
      limiting access to water to 30 min/d in the morning. Drinking after single or
      repeated restriction increased Fos, demonstrating increased NTS activity. We next
      examined the contribution of the vagus by comparing hormonal responses after
      total subdiaphragmatic vagotomy or sham surgery. Water restriction for 6 d
      increased plasma arginine vasopressin (AVP), ACTH, and adrenal and plasma
      corticosterone in both groups. In sham rats, drinking reduced plasma AVP, ACTH,
      adrenal and plasma corticosterone by 7.5 min. In total subdiaphragmatic vagotomy
      rats, whereas drinking reduced plasma AVP, ACTH, and adrenal corticosterone,
      drinking did not reduce plasma corticosterone. To identify the source of vagal
      activity, hormonal responses to restriction-induced drinking were measured after
      common hepatic branch vagotomy (HBV). Although pituitary hormonal responses were
      not affected by HBV, the adrenal and plasma corticosterone responses to water
      restriction were reduced; in addition, drinking in HBV rats decreased adrenal
      corticosterone without changing plasma corticosterone. These data indicate that
      an intact vagus is necessary to reduce plasma corticosterone when water
      restricted rats drink and that the common hepatic vagal branch contributes to the
      response. These findings implicate the vagus in augmenting rapid removal of
      circulating corticosterone during relief from stress.

PMID- 19106214
TI  - Antagonism of oxytocin prevents suckling- and estradiol-induced, but not
      progesterone-induced, secretion of prolactin.
AB  - In female rats, estradiol (E(2)) and suckling induce prolactin (PRL) secretion.
      This involves inhibition of hypothalamic dopaminergic tone and stimulation by a
      PRL-releasing hormone, possibly oxytocin (OT). Infusing an OT antagonist (OTA)
      i.v., we evaluated the role of OT on suckling- and E(2)-induced PRL secretion.
      Three days after parturition at 0900 h, lactating dams were fitted with 24-h
      osmotic minipumps filled with saline or OTA. On d 5 of lactation, pups were
      separated from their dams for 6 h. Immediately or 20 min after the resumption of
      suckling, dam trunk blood was collected. Also, ovariectomized (OVX) rats were
      treated with E(2) (OVE) and OTA at 1000 h on d 1. Blood samples were obtained
      from 1300 to 2100 h on d 2 for PRL measurements. Additionally, OVX rats were
      evaluated on d 2 after receiving progesterone (P(4)). OTA blocked suckling and
      E(2)-induced release of PRL but not that induced by E(2)+P(4). Pups from treated
      dams failed to gain weight when allowed to nurse for 20 min on d 5 but gained
      more than 7 g when nursed on d 7 of lactation, indicating that the OTA was active
      48 h later. Western blot analysis showed that E(2) treatment increased OT
      receptors in the anterior pituitary when compared with OVX animals. No further
      increase was observed in response to the P(4), suggesting that the enhancing
      effect of P(4) on E(2)-induced PRL release may act through mechanisms independent
      of OT. These data demonstrate the role of OT in the control of suckling and
      steroid-induced PRL secretion.

PMID- 19106216
TI  - Conditional transgenic mice for studying the role of the glucocorticoid receptor
      in the renal collecting duct.
AB  - The mineralocorticoid receptor (MR) is a major regulator of renal sodium
      reabsorption and body fluid homeostasis. However, little is known about
      glucocorticoid receptor (GR)-dependent renal effects. Glucocorticoids may
      activate both receptors, so it is difficult to distinguish between MR- and GR
      mediated effects in vivo. To overcome this complexity, we used a transgenic mouse
      model allowing conditional GR overexpression (doxycycline inducible TetON system,
      Hoxb7 promoter) in the renal collecting duct (CD) to identify GR-regulated genes
      involved in sodium transport in the CD. In microdissected cortical CD, induction
      of GR expression led (after 2 d of doxycycline) to increased alpha-epithelial
      sodium channel and glucocorticoid-induced leucine zipper and decreased abundance
      of with-no-lysine kinase 4 transcripts, without modification of Na,K-ATPase,
      serum- and glucocorticoid-kinase-1, or MR expression. No changes occurred in the
      upstream distal and connecting tubules [distal convoluted tubule (DCT),
      connecting tubule (CNT)]. Sodium excretion was unaltered, but the urinary
      aldosterone concentration was reduced, suggesting compensation of transitory
      extracellular volume expansion that subsequently disappeared. At steady state,
      i.e. after 15 d of doxycycline administration, transcript abundance remained
      altered in the CD, whereas mirror changes appeared in the DCT and CNT. Plasma
      aldosterone or glucocorticoids and blood pressure were all unaffected. These
      experiments show that: 1) GR, in addition to MR, controls epithelial sodium
      channel- and glucocorticoid-induced leucine zipper expression in vivo in the CD;
      2) with-no-lysine kinase 4 is negatively controlled by GR; and 3) the DCT and CNT
      compensate for these alterations to maintain normal sodium reabsorption and blood
      pressure. These results suggest that enhanced GR expression may contribute to
      enhanced sodium retention in some pathological situations.

PMID- 19106217
TI  - Potential role of growth hormone in impairment of insulin signaling in skeletal
      muscle, adipose tissue, and liver of rats chronically treated with arginine.
AB  - We have shown that rats chronically treated with Arginine (Arg), although
      normoglycemic, exhibit hyperinsulinemia and decreased blood glucose disappearance
      rate after an insulin challenge. Attempting to investigate the processes
      underlying these alterations, male Wistar rats were treated with Arg (35 mg/d),
      in drinking water, for 4 wk. Rats were then acutely stimulated with insulin, and
      the soleus and extensorum digitalis longus muscles, white adipose tissue (WAT),
      and liver were excised for total and/or phosphorylated insulin receptor (IR), IR
      substrate 1/2, Akt, Janus kinase 2, signal transducer and activator of
      transcription (STAT) 1/3/5, and p85alpha/55alpha determination. Muscles and WAT
      were also used for plasma membrane (PM) and microsome evaluation of glucose
      transporter (GLUT) 4 content. Pituitary GH mRNA, GH, and liver IGF-I mRNA
      expression were estimated. It was shown that Arg treatment: 1) did not affect
      phosphotyrosine-IR, whereas it decreased phosphotyrosine-IR substrate 1/2 and
      phosphoserine-Akt content in all tissues studied, indicating that insulin
      signaling is impaired at post-receptor level; 2) decreased PM GLUT4 content in
      both muscles and WAT; 3) increased the pituitary GH mRNA, GH, and liver IGF-I
      mRNA expression, the levels of phosphotyrosine-STAT5 in both muscles,
      phosphotyrosine-Janus kinase 2 in extensorum digitalis longus, phosphotyrosine
      STAT3 in liver, and WAT as well as total p85alpha in soleus, indicating that GH
      signaling is enhanced in these tissues; and 4) increased p55alpha total content
      in muscles, WAT, and liver. The present findings provide the molecular mechanisms
      by which insulin resistance and, by extension, reduced GLUT4 content in PM of
      muscles and WAT take place after chronic administration of Arg, and further
      suggest a putative role for GH in its genesis, considering its diabetogenic
      effect.

PMID- 19106218
TI  - Ca2+-activated K+ channels in gonadotropin-releasing hormone-stimulated mouse
      gonadotrophs.
AB  - GnRH receptor activation elicits release of intracellular Ca(2+), which leads to
      secretion and also activates Ca(2+)-activated ion channels underlying membrane
      voltage changes. The predominant Ca(2+)-activated ion channels in rat and mouse
      gonadotrophs are Ca(2+)-activated K(+) channels. To establish the temporal
      relationship between GnRH-induced changes in intracellular [Ca(2+)] ([Ca(2+)](i))
      and membrane current (I(m)), and to identify specific Ca(2+)-activated K(+)
      channels linking GnRH-induced increase in [Ca(2+)](i) to changes in plasma
      membrane electrical activity, we used single female mouse gonadotrophs in the
      perforated patch configuration of the patch-clamp technique, which preserves
      signaling pathways. Simultaneous measurement of [Ca(2+)](i) and I(m) in voltage
      clamped gonadotrophs revealed that GnRH stimulates an increase in [Ca(2+)](i)
      that precedes outward I(m), and that activates two kinetically distinct currents
      identified, using specific toxin inhibitors, as small conductance Ca(2+)
      activated K(+) (SK) current (I(SK)) and large (big) conductance voltage- and
      Ca(2+)-activated K(+) (BK) current (I(BK)). We show that the apamin-sensitive
      current has an IC(50) of 69 pM, consistent with the SK2 channel subtype and
      confirmed by immunocytochemistry. The magnitude of the SK current response to
      GnRH was attenuated by 17beta-estradiol (E(2)) pretreatment. Iberiotoxin, an
      inhibitor of BK channels, completely blocked the residual apamin-insensitive
      outward I(m), substantiating that I(BK) is a component of the GnRH-induced
      outward I(m). In contrast to its suppression of I(SK), E(2) pretreatment
      augmented peak I(BK). SK or BK channel inhibition modulated GnRH-stimulated LH
      secretion, implicating a role for these channels in gonadotroph function. In
      summary, in mouse gonadotrophs the GnRH-stimulated increase in [Ca(2+)](i)
      activates I(SK) and I(BK), which are differentially regulated by E(2) and which
      may be targets for E(2) positive feedback in LH secretion.

PMID- 19106220
TI  - Endogenous aldosterone contributes to acute angiotensin II-stimulated plasminogen
      activator inhibitor-1 and preproendothelin-1 expression in heart but not aorta.
AB  - To test the hypothesis that angiotensin (Ang) II induces profibrotic gene
      expression through endogenous aldosterone, we measured the effect of 4 h infusion
      (600 ng/kg x min) of Ang II on tissue mRNA expression of plasminogen activator
      inhibitor 1 (PAI-1), preproendothelin-1 (ppET-1), TGF-beta, and osteopontin in
      wild-type (WT), aldosterone synthase-deficient (AS(-/-)), and AS(-/-) mice
      treated with aldosterone (either 500 ng/d for 7 d or 250 ng as a concurrent 4 h
      infusion). Ang II increased aldosterone in WT (P < 0.001) but not in AS(-/-)
      mice. Aldosterone (7 d) normalized basal aldosterone concentrations in AS(-/-)
      mice; however, there was no further effect of Ang II on aldosterone (P = NS).
      Basal cardiac and aortic PAI-1 and ppET-1 expression were similar in WT and AS(-/
      ) mice. Ang II-stimulated PAI-1 (P < 0.001) and ppET-1 expression (P = 0.01) was
      diminished in the heart of AS(-/-) mice; treatment with aldosterone for 4 h or 7
      d restored PAI-1 and ppET-1 mRNA responsiveness to Ang II in the heart. Ang II
      increased PAI-1 (P = 0.01) expression in the aorta of AS(-/-) as well as WT mice.
      In the kidney, basal PAI-1, ppET-1, and TGF-beta mRNA expression was increased in
      AS(-/-) compared with WT mice and correlated with plasma renin activity. Ang II
      did not stimulate osteopontin or TGF-beta expression in the heart or kidney.
      Endogenous aldosterone contributes to the acute stimulatory effect of Ang II on
      PAI-1 and ppET-1 mRNA expression in the heart; renin activity correlates with
      basal profibrotic gene expression in the kidney.

PMID- 19106219
TI  - Palatable foods, stress, and energy stores sculpt corticotropin-releasing factor,
      adrenocorticotropin, and corticosterone concentrations after restraint.
AB  - Previous studies have shown reduced hypothalamo-pituitary-adrenal responses to
      both acute and chronic restraint stressors in rats allowed to ingest highly
      palatable foods (32% sucrose +/- lard) prior to restraint. In this study we
      tested the effects of prior access (7 d) to chow-only, sucrose/chow, lard/chow,
      or sucrose/lard/chow diets on central corticotropin-releasing factor (CRF)
      expression in rats studied in two experiments, 15 and 240 min after onset of
      restraint. Fat depot, particularly intraabdominal fat, weights were increased by
      prior access to palatable food, and circulating leptin concentrations were
      elevated in all groups. Metabolite concentrations were appropriate for values
      obtained after stressors. For unknown reasons, the 15-min experiment did not
      replicate previous results. In the 240-min experiment, ACTH and corticosterone
      responses were inhibited, as previously, and CRF mRNA in the hypothalamus and
      oval nucleus of the bed nuclei of the stria terminalis were reduced by palatable
      foods, suggesting strongly that both neuroendocrine and autonomic outflows are
      decreased by increased caloric deposition and palatable food. In the central
      nucleus of the amygdala, CRF was increased in the sucrose-drinking group and
      decreased in the sucrose/lard group, suggesting that the consequence of ingestion
      of sucrose uses different neural networks from the ingestion of lard. The results
      suggest strongly that ingestion of highly palatable foods reduces activity in the
      central stress response network, perhaps reducing the feeling of stressors.

PMID- 19106221
TI  - Estradiol and tamoxifen mediate rescue of the dominant-negative effects of
      estrogen response element-binding protein in vivo and in vitro.
AB  - Biological responses to estrogens are dependent on the integrated actions of
      proteins, including the estrogen receptor (ER)-alpha, that regulate the
      transcription of estrogen response element (ERE)-containing target genes. We have
      identified a naturally occurring ERE antagonist, termed an ERE-binding protein
      (BP). To verify that ERE-BP can induce estradiol (E(2)) resistance in vivo, we
      generated transgenic mice that overexpress this protein in breast tissue. Female
      transgenic mice with high levels of ERE-BP were unable to lactate, and we
      hypothesized that this effect was dependent on the relative levels of ERE-BP and
      ERalpha ligand. To test this hypothesis, wild-type and ERE-BP-expressing female
      mice were implanted with capsules containing E(2), the selective estrogen
      receptor modulator tamoxifen, or placebo. Histological analysis of nonlactating
      mammary glands showed a 4.5-fold increase in gland branch number and 3.7-fold
      increase in ducts in ERE-BP mice treated with E(2) (7.5 mg, 21 d) compared with
      placebo-treated ERE-BP mice. Wild-type mice showed a 5.3-fold increase in
      branches and 1.4-fold increase in ducts under the same conditions. Similar
      results were obtained with tissue from lactating mice, in which tamoxifen also
      increased mammary gland branch number. Studies using ERE-BP-expressing MCF-7
      breast cells showed that high doses of E(2) (1000 nM) restored normal ERalpha
      chromatin interaction in these cells, whereas tamoxifen was able to achieve this
      effect at a dose of 10 nM. These data highlight the importance of ERE-BP as an
      attenuator of normal ERalpha signaling in vivo and further suggest that ERE-BP is
      a novel target for modulation by selective estrogen receptor modulators.

PMID- 19106222
TI  - Role of the Rho-ROCK (Rho-associated kinase) signaling pathway in the regulation
      of pancreatic beta-cell function.
AB  - Extracellular matrix has a beneficial impact on beta-cell spreading and function,
      but the underlying signaling pathways have yet to be fully elucidated. In other
      cell types, Rho, a well-characterized member of the family of Rho GTPases, and
      its effector Rho-associated kinase (ROCK), play an important role as downstream
      mediators of outside in signaling from extracellular matrix. Therefore, a
      possible role of the Rho-ROCK pathway in beta-cell spreading, actin cytoskeleton
      dynamics, and function was investigated. Rho was inhibited using a new cell
      permeable version of C3 transferase, whereas the activity of ROCK was repressed
      using the specific ROCK inhibitors H-1152 and Y-27632. Inhibition of Rho and of
      ROCK increased spreading and improved both short-term and prolonged glucose
      stimulated insulin secretion but had no impact on basal secretion. Inhibition of
      this pathway led to a depolymerization of the actin cytoskeleton. Furthermore,
      the impact of the inhibition of ROCK on stimulated insulin secretion was acute
      and reversible, suggesting that rapid signaling such as phosphorylation is
      involved. Finally, quantification of the activity of RhoA indicated that the
      extracellular matrix represses RhoA activity. Overall these results show for the
      first time that the Rho-ROCK signaling pathway contributes to the stabilization
      of the actin cytoskeleton and inhibits glucose-stimulated insulin secretion in
      primary pancreatic beta-cells. Furthermore, they indicate that inhibition of this
      pathway might be one of the mechanisms by which the extracellular matrix exerts
      its beneficial effects on pancreatic beta-cell function.

PMID- 19106223
TI  - The secretogranin II-derived peptide secretoneurin stimulates luteinizing hormone
      secretion from gonadotrophs.
AB  - Secretoneurin (SN) is a 33- to 34-amino acid neuropeptide derived from
      secretogranin-II, a member of the chromogranin family. We previously synthesized
      a putative goldfish (gf) SN and demonstrated its ability to stimulate LH release
      in vivo. However, it was not known whether goldfish actually produced the free SN
      peptide or whether SN directly stimulates LH release from isolated pituitary
      cells. Using a combination of reverse-phase HPLC and mass spectrometry analysis,
      we isolated for the first time a 34-amino acid free gfSN peptide from the whole
      brain. Moreover, Western blot analysis indicated the existence of this peptide in
      goldfish pituitary. Immunocytochemical localization studies revealed the presence
      of SN immunoreactivity in prolactin cells of rostral pars distalis of the
      anterior pituitary. Additionally, we found that magnocellular cells of the
      goldfish preoptic region are highly immunoreactive for SN. These neurons send
      heavily labeled projections that pass through the pituitary stalk and innervate
      the neurointermediate and anterior lobes. In static 12-h incubation of dispersed
      pituitary cells, application of SN antiserum reduced LH levels, whereas 1 and 10
      nM gfSN, respectively, induced 2.5-fold (P < 0.001) and 1.9-fold (P < 0.01)
      increments of LH release into the medium, increases similar to those elicited by
      100 nM concentrations of GnRH. Like GnRH, gfSN elevated intracellular Ca(2+) in
      identified gonadotrophs. Whereas we do not yet know the relative contribution of
      neural SN or pituitary SN to LH release, we propose that SN could act as a
      neuroendocrine and/or paracrine factor to regulate LH release from the anterior
      pituitary.

PMID- 19106224
TI  - Growth differentiation factor 9 is a germ cell regulator of Sertoli cell
      function.
AB  - Oocyte-secreted growth differentiation factor (GDF) 9 and bone morphogenetic
      protein (BMP) 15 are critical regulatory factors in female reproduction.
      Together, they promote granulosa cell proliferation and stimulate the maturation
      of preovulatory follicles. Despite their importance in female fertility, GDF9 and
      BMP15 expression patterns and function during spermatogenesis have not been
      investigated. In this study we show that the expression and stage-specific
      localization of both factors are limited to the germ cells of the rat
      seminiferous epithelium, with GDF9 being principally localized in round
      spermatids and BMP15 in gonocytes and pachytene spermatocytes. To identify
      potential cellular targets for GDF9 actions, cells of the seminiferous tubule
      were isolated and screened for the expression of signaling receptors [activin
      like kinase (ALK) 5, ALK6, and BMP receptor, type II)]. Individual receptor types
      were expressed throughout the seminiferous epithelium, but coexpression of ALK5
      and BMP receptor, type II was limited to Sertoli cells and round spermatids.
      Based on the reproductive actions of related TGFbeta ligands in the ovary and
      testis, GDF9 was assessed for its ability to regulate tight junction function and
      inhibin B production in rat Sertoli cell cultures. When recombinant mouse GDF9
      was added to immature Sertoli cell cultures, it inhibited membrane localization
      of the junctional proteins claudin-11, occludin, and zonula occludens-1, thereby
      disrupting tight junction integrity. Concomitantly, GDF9 up-regulated inhibin
      subunit expression and significantly stimulated dimeric inhibin B protein
      production. Together, these results demonstrate that GDF9 and BMP15 are germ cell
      specific factors in the rat testis, and that GDF9 can modulate key Sertoli cell
      functions.

PMID- 19106226
TI  - Persistent impairment of hypothalamic KiSS-1 system after exposures to estrogenic
      compounds at critical periods of brain sex differentiation.
AB  - Attainment of reproductive capacity at puberty relies on a complex series of
      maturational events that include sexual differentiation of the brain; a
      hormonally driven phenomenon that takes place at early stages of development
      (critical period). Alterations of sex steroid milieu during such critical period
      disrupt pubertal maturation and gonadotropic function later in life, through
      mechanisms that remain partially unknown. Kisspeptins, products of the KiSS-1
      gene acting via G protein-coupled receptor 54, have recently emerged as essential
      gatekeepers of puberty onset and reproductive function. By using rat models of
      neonatal administration of estrogenic compounds, we provide herein compelling
      evidence for the functional impairment of the hypothalamic KiSS-1 system at the
      time preceding puberty after early inappropriate exposures during brain sex
      differentiation. Neonatal injection of estradiol benzoate to male and female rats
      resulted in a dose-dependent decrease in hypothalamic KiSS-1 mRNA levels at the
      prepubertal stage, linked to lowering of serum LH concentrations. Yet, despite
      persistently decreased basal gonadotropin levels in estrogenized animals,
      intracerebral injection of kisspeptin evoked potent LH and FSH secretory
      responses, similar in magnitude to those of control animals. Estrogenized rats
      also showed defective levels of hypothalamic KiSS-1 mRNA and circulating
      gonadotropins in response to gonadectomy, whereas exogenous kisspeptin was
      capable to enhance further LH and FSH secretion in this model. Finally, protocols
      of neonatal exposure to high doses of an environmentally relevant estrogen,
      bisphenol-A, mimicked the effects of estradiol benzoate in terms of hypothalamic
      expression of KiSS-1 gene at the prepubertal period. Altogether, our data
      document the sensitivity of the hypothalamic KiSS-1 system to alterations in sex
      steroid milieu during critical periods of brain sex differentiation, and suggest
      that lowering of endogenous kisspeptin tone induced by early exposures to xeno
      estrogens might be mechanistically relevant for disruption of gonadotropin
      secretion and puberty onset later in life.

PMID- 19106225
TI  - Progesterone Inhibits basal and gonadotropin-releasing hormone induction of
      luteinizing hormone beta-subunit gene expression.
AB  - LH and FSH play critical roles in mammalian reproduction by mediating
      steroidogenesis and gametogenesis in the gonad. Gonadal steroid hormone feedback
      to the hypothalamus and pituitary influences production of the gonadotropins. We
      previously demonstrated that progesterone differentially regulates the expression
      of the LH and FSH beta-subunits at the level of the gonadotrope: FSHbeta
      transcription is induced, whereas LHbeta is repressed. In this study, we
      investigated the mechanism of progesterone repression of LHbeta gene expression
      using immortalized gonadotrope-derived LbetaT2 cells. The progesterone
      suppression of both basal and GnRH-induced LHbeta gene expression occurs in a
      hormone- and receptor-dependent manner. Chromatin immunoprecipitation
      demonstrates that the hormone-bound progesterone receptor (PR) is recruited to
      the endogenous mouse LHbeta promoter. In addition, suppression requires both the
      amino-terminal and DNA-binding regions of PR. Furthermore, progesterone
      suppression does not require direct PR binding to the promoter, and, thus, PR is
      likely recruited to the promoter via indirect binding through other transcription
      factors. These data demonstrate that the molecular mechanism for progesterone
      action on the LHbeta promoter is distinct from FSHbeta, which involves direct PR
      binding to the promoter to produce activation. It also differs from androgen
      repression of LHbeta gene expression in that, rather than Sp1 or steroidogenic
      factor-1 elements, it requires elements within -300/-250 and -200/-150 that also
      contribute to basal expression of the LHbeta promoter. Altogether, our data
      indicate that progesterone feedback at the level of the pituitary gonadotrope is
      likely to play a key role in differential production of the gonadotropin genes.

PMID- 19106227
TI  - Somatostatin actions via somatostatin receptors on the ocular surface are
      modulated by inflammatory processes.
AB  - Recent investigations support the presence of human somatostatin (SS) in the
      excretory system of the human lacrimal gland. To get deeper insights into a
      possible role of SS at the ocular surface and in the lacrimal apparatus, we
      investigated the distribution pattern of SS and its receptors 1-5 (SSTR1-5) by
      means of RT-PCR, real-time RT-PCR, Western blot and immunodot blot analysis as
      well as immunohistochemistry in lacrimal gland, tear fluid, conjunctiva, cornea,
      nasolacrimal duct epithelium, and conjunctival (HCjE) and corneal (HCE)
      epithelial cell lines. Cell culture experiments with HCjE and HCE were performed
      to analyze a possible impact of SS and inflammatory mediators on the regulation
      of SSTR. The results confirmed the presence of SS in lacrimal gland and tear
      fluid, whereas it was absent at the protein level in all other tissues and cell
      lines investigated. Expression of SSTR1, -2, and -5 was detectable in lacrimal
      gland, conjunctiva, cornea, and nasolacrimal ducts. HCjE expressed only hSSTR1
      and -2, and HCE revealed only SSTR2. SSTR3 and -4 were not detected in any of the
      analyzed samples or cell lines. In vitro on cultured immortalized HCjE cells SS
      leads to a concentration-dependent down-regulation of SSTR1 mRNA but does not
      affect SSTR2 mRNA expression. Relative expression of SSTR1 and -2 is
      differentially modulated by proinflammatory cytokines and bacterial components,
      suggesting that the expression of both receptors is immunomodulated. Our data
      support an autocrine and paracrine role of SS in the lacrimal system and at the
      ocular surface and implicate a role of SS in corneal immunology.

PMID- 19106228
TI  - The heme oxygenase system abates hyperglycemia in Zucker diabetic fatty rats by
      potentiating insulin-sensitizing pathways.
AB  - Emerging evidence indicates that aldosterone causes oxidative stress by
      stimulating proinflammatory/oxidative mediators, including nuclear factor-kappaB,
      activating protein (AP-1), and c-Jun N-terminal kinase. Thus, in insulin
      resistant type 2 diabetes (T2D), oxidative stress generated by hyperglycemia and
      aldosterone would potentiate the oxidative destruction of tissue and important
      regulators of glucose metabolism like adiponectin and insulin. Although heme
      oxygenase (HO)-1 is cytoprotective, its effects on T2D have not been fully
      characterized. Here we report an enduring antidiabetic effect of the HO inducer,
      hemin, on Zucker diabetic-fatty rat (ZDF), a model of insulin-resistant T2D.
      Chronically applied hemin to ZDF reduced and maintained significantly low fasting
      and postprandial hyperglycemia for 4 months after therapy. The antidiabetic
      effect was accompanied by enhanced HO activity, catalase, cyclic GMP, bilirubin,
      ferritin, total antioxidant capacity, and insulin. In contrast, reduced
      aldosterone alongside markers/mediators of oxidative stress, including 8
      isoprostane, c-Jun N-terminal kinase, nuclear factor-kappaB, AP-1, and AP-2 were
      observed. Interestingly, in hemin-treated ZDF, inhibitory proteins of insulin
      signaling, such as glycogen synthase kinase-3 and protein-tyrosine phosphatase-1B
      were reduced, whereas agents that promote insulin signaling including
      adiponectin, cAMP, AMP-activated protein kinase, aldolase-B, and glucose
      transporter-4 (GLUT4), were robustly increased. Correspondingly, hemin improved
      ip glucose tolerance, reduced insulin intolerance, and lowered insulin resistance
      (homeostasis model assessment of insulin resistance), and the inability of
      insulin to enhance GLUT4 was overturned. These results suggest that the
      suppression of hyperglycemia and aldosterone-induced oxidative stress alongside
      the potentiation of insulin-sensitizing pathways may account for the 4-month
      enduring antidiabetic effect. The synergistic interaction between the HO system,
      aldolase-B, adiponectin, AMP-activated protein kinase, and GLUT4 may be explored
      for novel strategies against postprandial/fasting hyperglycemia and insulin
      resistant T2D.

PMID- 19106229
TI  - Desipramine reduces stress-activated dynorphin expression and CREB
      phosphorylation in NAc tissue.
AB  - The nucleus accumbens (NAc) is a critical brain area for reward and motivated
      behavior. Accumulating evidence suggests that altered function of the
      transcription factor cAMP response element binding protein (CREB) within the NAc
      is involved in depressive behavior. In rats, stress activates CREB within the
      NAc, and elevation of CREB expression in this region produces depressive-like
      behaviors that are accompanied by activation of CREB-regulated target genes. The
      depressive-like behaviors seem to be due, at least in part, to CREB-mediated
      increases in dynorphin function, because they are mimicked by kappa-opioid
      receptor (KOR) agonists and attenuated by KOR antagonists. We hypothesized that
      if CREB-mediated dynorphin expression in the NAc contributes to depressive
      behavior, then antidepressants might reduce dynorphin function in this region.
      Here, we demonstrate that desipramine (DMI), a norepinephrine reuptake inhibitor
      that has been used for decades to treat clinical depression, blocks swim stress
      induced activation of prodynorphin (encodes dynorphin) in the NAc. In primary
      cultures of NAc and striatum, DMI decreases basal and stimulated CREB
      phosphorylation by causing reductions in intracellular calcium (Ca(2+))
      availability that are independent of norepinephrine or other monoaminergic
      inputs, identifying a potential mechanism for alterations in CREB-mediated gene
      expression. Fluoxetine (FLX), a selective serotonin reuptake inhibitor, has
      similar effects in culture, suggesting a common intracellular effect of these
      antidepressants. These findings raise the possibility that a therapeutically
      relevant mechanism of action of DMI occurs through attenuation of CREB-mediated
      gene transcription, which is mediated via previously uncharacterized mechanisms
      that occur directly within the NAc.

PMID- 19106230
TI  - Fluorescence resonance energy transfer analysis of alpha 2a-adrenergic receptor
      activation reveals distinct agonist-specific conformational changes.
AB  - Several lines of evidence suggest that G-protein-coupled receptors can adopt
      different active conformations, but their direct demonstration in intact cells is
      still missing. Using a fluorescence resonance energy transfer (FRET)-based
      approach we studied conformational changes in alpha(2A)-adrenergic receptors in
      intact cells. The receptors were C-terminally labeled with cyan fluorescent
      protein and with fluorescein arsenical hairpin binder at different sites in the
      third intracellular loop: N-terminally close to transmembrane domain V (I3-N), in
      the middle of the loop (I3-M), or C-terminally close to transmembrane domain VI
      (I3-C). All constructs retained normal ligand binding and signaling properties.
      Changes in FRET between the labels were determined in intact cells in response to
      different agonists. The full agonist norepinephrine evoked similar FRET changes
      for all three constructs. The strong partial agonists clonidine and dopamine
      induced partial FRET changes for all constructs. However, the weak partial
      agonists octopamine and norphenephrine only induced detectable changes in the
      construct I3-C but no change in I3-M and I3-N. Dopamine-induced FRET-signals were
      approximately 1.5-fold slower than those for norepinephrine in I3-C and I3-M but
      >3-fold slower in I3-N. Our data indicate that the different ligands induced
      conformational changes in the receptor that were sensed differently in different
      positions of the third intracellular loop. This agrees with X-ray receptor
      structures indicating larger agonist-induced movements at the cytoplasmic ends of
      transmembrane domain VI than V and suggests that partial agonism is linked to
      distinct conformational changes within a G-protein-coupled receptor.

PMID- 19106231
TI  - Quantitative PET reporter gene imaging of CD8+ T cells specific for a melanoma
      expressed self-antigen.
AB  - Adoptive transfer (AT) T-cell therapy provides significant clinical benefits in
      patients with advanced melanoma. However, approaches to non-invasively visualize
      the persistence of transferred T cells are lacking. We examined whether positron
      emission tomography (PET) can monitor the distribution of self-antigen-specific T
      cells engineered to express an herpes simplex virus 1 thymidine kinase (sr39tk)
      PET reporter gene. Micro-PET imaging using the sr39tk-specific substrate 9-[4
      [(18)F]fluoro-3-(hydroxymethyl)-butyl]guanine ([(18)F]FHBG) enabled the detection
      of transplanted T cells in secondary lymphoid organs of recipient mice over a 3
      week period. Tumor responses could be predicted as early as 3 days following AT
      when a >25-fold increase of micro-PET signal in the spleen and 2-fold increase in
      lymph nodes (LNs) were observed in mice receiving combined immunotherapy versus
      control mice. The lower limit of detection was approximately 7 x 10(5) T cells in
      the spleen and 1 x 10(4) T cells in LNs. Quantification of transplanted T cells
      in the tumor was hampered by the sr39tk-independent trapping of [(18)F]FHBG
      within the tumor architecture. These data support the feasibility of using PET to
      visualize the expansion, homing and persistence of transferred T cells. PET may
      have significant clinical utility by providing the means to quantify anti-tumor T
      cells throughout the body and provide early correlates for treatment efficacy.

PMID- 19106232
TI  - Altered production of immunoregulatory cytokines by invariant Valpha19 TCR
      bearing cells dependent on the duration and intensity of TCR engagement.
AB  - Cells bearing invariant Valpha19-Jalpha33 TCR alpha chains are believed to
      participate in the regulation of inflammatory autoimmune diseases. In this study,
      the potential to produce immunoregulatory cytokines by these cells was
      characterized in order to find the mechanism underlying their immunoregulatory
      functions. Serum levels of IL-4, IL-10, transforming growth factor-beta, IFN
      gamma and IL-17 increased in mice over-expressing an invariant Valpha19-Jalpha33
      TCR alpha transgene (Valpha19 Tg) in response to anti-CD3 antibody injection.
      NK1.1(+) Valpha19 Tg(+), but not NK1.1(-) Valpha19 Tg(+) cells, promptly produced
      immunoregulatory IL-4, IFN-gamma and IL-17 upon invariant TCR engagement with
      immobilized anti-CD3 antibody in culture. The activation of Valpha19 Tg(+) cells
      then triggered the production of pro-inflammatory cytokines by bystander cells.
      Interestingly, the ratio of T(h)2 cytokines such as IL-4, IL-5 and IL-10, but not
      pro-inflammatory IL-17, to IFN-gamma was increased when the intensity of the
      stimulation to invariant TCR was attenuated. Collectively, these findings suggest
      that invariant Valpha19 TCR(+) cells have the potential to participate in the
      regulation of inflammatory autoimmunity by producing T(h)2-biased cytokines in
      certain circumstances.

PMID- 19106233
TI  - Pharmacological profiles of animal- and nonanimal-derived sulfated
      polysaccharides--comparison of unfractionated heparin, the semisynthetic glucan
      sulfate PS3, and the sulfated polysaccharide fraction isolated from Delesseria
      sanguinea.
AB  - Sulfated polysaccharides (SP) such as heparin are known to exhibit a wide range
      of biological activities, e.g., anticoagulant, anti-inflammatory, and
      antimetastastic effects. However, since the anticoagulant activity of heparin is
      dominating, its therapeutic use for other medical indications is limited due to
      an associated risk of bleeding. Further disadvantages of heparin are its animal
      origin, the shortage of resources, and its complex and variable composition.
      However, SP without these limitations may represent a substance class with good
      prospects for applications other than anticoagulation. In this study, the in
      vitro pharmacological profiles of two nonanimal-derived SP were investigated in
      comparison with unfractionated heparin. One is the natural SP fraction from the
      red algae Delesseria sanguinea (D.s.-SP). The other one is the chemically defined
      PS3, a semisynthetic beta-1,3-glucan sulfate with proven in vivo anti
      inflammatory and antimetastatic activities. All three polysaccharides were
      examined in vitro for their inhibitory effects on the coagulation and complement
      system, polymorphonuclear neutrophil elastase, hyaluronidase, matrix
      metalloproteinase-1, heparanase, and p-selectin-mediated cell adhesion. Compared
      with heparin, the nonanimal-derived polysaccharides have a four times weaker
      anticoagulant activity, but mostly exhibit stronger (1.4-224 times) effects on
      test systems investigating targets of inflammation or metastasis. According to
      their different structures, PS3 and D.s.-SP differ in their pharmacological
      profile with PS3 being the strongest inhibitor of heparanase and cell adhesion
      and D.s.-SP being the strongest inhibitor of hyaluronidase and complement
      activation. Considering both pharmacological profile and pharmaceutical quality
      parameters, PS3 represents a candidate for further development as an anti
      inflammatory or antimetastatic drug whereas D.s.-SP might have perspectives for
      cosmetic applications.

PMID- 19106234
TI  - Helicobacter pylori binding to new glycans based on N-acetyllactosamine.
AB  - Previously we reported binding of Helicobacter pylori to various nonacid and
      sialylated neolacto carbohydrate structures using a wide range of natural and
      chemically modified sequences. A novel nonsialylated neolacto-based binding
      epitope, GlcNAc beta 3Gal beta 4GlcNAc, and analogous structures carrying
      terminal GalNAc beta 3, GalNAc alpha 3, or Gal alpha 3 showed the binding
      activity (Miller-Podraza H, Lanne B, Angstrom J, Teneberg S, Abul-Milh M, Jovall
      P-A, Karlsson H, Karlsson K-A. 2005. Novel binding epitope for Helicobacter
      pylori found in neolacto carbohydrate chains. J Biol Chem. 280:19695-19703). The
      present work reports two other H. pylori-binding nonsialylated neolacto-based
      structures, GlcA beta 3Gal beta 4GlcNAc beta 3-R and Glc beta 3Gal beta 4GlcNAc
      beta 3-R, and two amide derivatives (N-methyl and N-ethyl) of GlcA beta 3Gal beta
      4GlcNAc beta 3-R which were bound by H. pylori. The latter structures turned out
      to be more effective as H. pylori binders than the parent saccharide. New
      reducing-end variants of the neolacto epitope including species containing N
      acetyllactosamine linked beta 6 to GlcNAc or Gal with similarity to branched
      polylactosamines and mucins were prepared and tested. The results extend our
      previous findings on binding specificities of H. pylori and show that this
      pathogen is able to interact with an array of N-acetyllactosamine/neolacto
      structures, which may be of importance for the in vivo interaction of the
      bacterium with human cells. The information gained in this work may also be of
      value for rational design of anti-H. pylori drugs.

PMID- 19106235
TI  - Prolonged oestrogen treatment does not correlate with a sustained increase in
      anterior pituitary mitotic index in ovariectomized Wistar rats.
AB  - Oestrogen is a powerful mitogen that is believed to exert a continuous, dose
      dependent trophic stimulus at the anterior pituitary. This persistent mitotic
      effect contrasts with corticosterone and testosterone, changes in the levels of
      which induce only transient, self-limiting fluctuations in pituitary mitotic
      activity. To further define the putative long-term trophic effects of oestrogen,
      we have accurately analysed the effects of 7 and 28 days oestrogen treatment on
      anterior pituitary mitotic activity in ovariectomized 10-week-old Wistar rats
      using both bromodeoxyuridine (BrdU) and timed colchicine-induced mitotic arrest.
      An oestrogen dose-dependent increase in mitotic index was seen 7 days after the
      start of treatment as expected, representing an acceleration in gross mitotic
      activity from 1.7%/day in ovariectomized animals in the absence of any oestrogen
      replacement to 3.7%/day in the presence of a pharmacological dose of oestrogen
      (50 mcg/rat per day: approximately 230 mcg/kg per day). Despite continued
      exposure to high-dose oestrogen and persistence of the increase in pituitary wet
      weight, the increase in mitotic index was unexpectedly not sustained. After 28
      days of high-dose oestrogen treatment, anterior pituitary mitotic index and BrdU
      labelling index were not significantly different from baseline. Although a
      powerful pituitary mitogen in the short term, responsible, presumably, for
      increased trophic variability in oestrus cycling females, these data indicate
      that in keeping with other trophic stimuli to the pituitary and in contrast to a
      much established dogma, the mitotic response to longer-term high-dose oestrogen
      exposure is transient and is not the driver of persistent pituitary growth, at
      least in female Wistar rats.

PMID- 19106236
TI  - Apolipoprotein A-I, A-II, C-II, and H expression in the developing lung and sex
      difference in surfactant lipids.
AB  - A sex difference in surfactant lipids is associated with a higher incidence of
      respiratory distress syndrome for males in cases of preterm birth. In animal
      models, the sex difference in surfactant lipids was shown to be androgen receptor
      dependent. This report examines expression of apolipoprotein (apo)A-I, apoA-II,
      apoC-II, apoE, apoH, and lipoprotein lipase (LPL) by quantitative real-time PCR
      in pools of male and female fetal lung tissues from various mouse litters from
      gestation day (GD) 15.5 to 18.5, and in various adult tissues. Although the
      expression profiles of ApoA-I, ApoA-II, ApoC-II, and ApoH are complex, these
      genes are co-regulated and they all present a sex difference (P=0.0896, 0.0896,
      0.0195, and 0.0607 respectively) with higher expression for females for several
      litters. Pulmonary expression of apoA-I, apoA-II, and apoH were specific to the
      developing lung. ApoE and LPL mRNAs showed a significant increase from GD 17.5 to
      18.5. An increase in apoA-I-, apoA-II-, apoC-II-, and apoH-mRNA accumulation was
      observed from GD 16.5 to 17.5 in correlation with the emergence of mature type II
      pneumonocytes. These four apolipoprotein genes are co-regulated with type 2 and 5
      17beta-hydroxysteroid dehydrogenases, which are respectively involved in
      inactivation and synthesis of androgens. Finally, apoC-II was detected by
      immunohistochemistry in epithelial cells of the distal epithelium. Positive
      signals looking like secretory granules were located near the basal membrane. Our
      results are compatible with a role for apolipoproteins in lipid metabolism and
      transport in the developing lung in association with the sex difference in
      surfactant lipid synthesis.

PMID- 19106237
TI  - Intergenerational influences on childhood body mass index: the effect of parental
      body mass index trajectories.
AB  - BACKGROUND: Parental obesity in adulthood is a strong determinant of offspring
      obesity. Whether parental body mass index (BMI; in kg/m2) at earlier life stages
      is associated with offspring BMI is unknown. OBJECTIVE: The main objective was to
      assess whether recent BMI of parents in adulthood and their recent BMI gain are
      more strongly associated with offspring BMI than are BMI or changes in parental
      BMI in childhood. DESIGN: Two generations in the 1958 British birth cohort were
      studied, including cohort members (parents' generation) with BMI at 7, 11, 16,
      23, and 33 y (n = 16,794) and a one-third sample of their offspring selected in
      1991 aged 4-18 y (n = 2908). We applied multilevel models to allow for within
      family correlations. RESULTS: Childhood BMI increased on average by 0.25-1.10
      between the 2 generations, depending on sex and age group, and overweight/obesity
      increased from 10% to 16%. Parents' BMI in childhood and adulthood independently
      influenced offspring BMI, but no significant difference in the strength of
      influence was observed. For example, adjusted increase in BMI for offspring aged
      4-8 y was equivalent to 0.37 and 0.23 for a 1-SD increase in maternal BMI at 7
      and 33 y, respectively. Similar patterns were observed for risk of
      overweight/obesity and for paternal BMI at most ages. CONCLUSIONS: Excessive BMI
      gains of parents during childhood and adulthood were associated with a higher BMI
      and risk of obesity in the offspring. Reductions in the incidence of child
      obesity in the current population may reduce obesity in future generations.

PMID- 19106238
TI  - Lactotripeptides do not lower ambulatory blood pressure in untreated whites:
      results from 2 controlled multicenter crossover studies.
AB  - BACKGROUND: Dietary factors directly influence blood pressure (BP). The
      lactotripeptides (LTPs) IPP (isoleucine-proline-proline) and VPP (valine-proline
      proline), formed by hydrolyzing dairy proteins, and potassium, a mineral mainly
      found in fruit, vegetables, and dairy products, are extensively studied for their
      BP-lowering effect. The efficacy of LTPs seems modest in whites compared with
      that in Asians. OBJECTIVE: The objective was to study the effects of
      enzymatically produced LTPs alone or in combination with potassium on ambulatory
      BP in whites. DESIGN: Two multicenter, placebo-controlled, randomized, crossover
      studies were conducted; each consisted of two 4-wk intervention periods separated
      by a 4-wk washout period. In study 1, 69 subjects received 200 g/d of a dairy
      drink with 5.8 mg IPP and 4.4 mg VPP or placebo. In study 2, 93 subjects received
      100 g/d of a dairy drink with 2.7 mg IPP, 1.9 mg VPP, and 350 mg added K or
      placebo. The subjects were randomly assigned according to their daytime
      ambulatory BP. RESULTS: Mean 24-h systolic and diastolic BP (baseline values
      study 1: 137.1/81.6 mm Hg; study 2: 139.2/80.9 mm Hg) remained similar with no
      significant differences between treatments in either study (P > 0.10). Office BP
      decreased over the course of both studies (systolic BP > 5 mm Hg), but
      differences between interventions were not significant (P > 0.10). In both
      studies, nighttime BP dipped during all treatments (> or =15%) but was
      statistically more significant with placebo (P < 0.05). Sodium excretion
      increased significantly after consumption of LTPs and potassium compared with
      after placebo intervention (P = 0.01), but not after consumption of LTPs alone.
      CONCLUSION: The data do not support a BP-lowering effect of LTPs in whites.

PMID- 19106239
TI  - Dietary flavonoids and circulating concentrations of nitrate, nitrite, and S
      nitrosothiols.

PMID- 19106240
TI  - Effects of a low-salt diet on flow-mediated dilatation in humans.
AB  - BACKGROUND: The effect of salt reduction on vascular function, assessed by
      brachial artery flow-mediated dilatation (FMD), is unknown. OBJECTIVE: Our aim
      was to compare the effects of a low-salt (LS; 50 mmol Na/d) diet with those of a
      usual-salt (US; 150 mmol Na/d) diet on FMD. DESIGN: This was a randomized
      crossover design in which 29 overweight and obese normotensive men and women
      followed an LS diet and a US diet for 2 wk. Both diets had similar potassium and
      saturated fat contents and were designed to ensure weight stability. After each
      intervention, FMD, pulse wave velocity, augmentation index, and blood pressure
      were measured. RESULTS: FMD was significantly greater (P = 0.001) with the LS
      diet (4.89 +/- 2.42%) than with the US diet (3.37 +/- 2.10%), systolic blood
      pressure was significantly (P = 0.02) lower with the LS diet (112 +/- 11 mm Hg)
      than with the US diet (117 +/- 13 mm Hg), and 24-h sodium excretion was
      significantly lower (P = 0.0001) with the LS diet (64.1 +/- 41.3 mmol) than with
      the US diet (156.3 +/- 56.7 mmol). There was no correlation between change in FMD
      and change in 24-h sodium excretion or change in blood pressure. No significant
      changes in augmentation index or pulse wave velocity were observed. CONCLUSIONS:
      Salt reduction improves endothelium-dependant vasodilation in normotensive
      subjects independently of the changes in measured resting clinic blood pressure.
      These findings suggest additional cardioprotective effects of salt reduction
      beyond blood pressure reduction. The trial is registered with the Australian and
      New Zealand Clinical Trials Registry (unique identifier: ANZCTR12607000381482;
      http://www.anzctr.org.au/trial_view.aspx?ID=82159).

PMID- 19106241
TI  - Association of diet with glycated hemoglobin during intensive treatment of type 1
      diabetes in the Diabetes Control and Complications Trial.
AB  - BACKGROUND: Persons with type 1 diabetes have received widely varying dietary
      advice based on putative effects on glycemic control. OBJECTIVE: The objective
      was to determine whether diet composition was associated with subsequent glycated
      hemoglobin (Hb A1c) concentrations during intensive therapy for type 1 diabetes.
      DESIGN: We examined associations between quantiles of dietary intake and Hb A1c
      adjusted for age and sex in 532 intensively treated participants in the Diabetes
      Control and Complications Trial (DCCT) who had complete dietary data through 5 y
      of follow-up. Multivariate macronutrient density linear regression models tested
      the association of Hb A1c at year 5 with macronutrient composition and were
      adjusted for age, sex, exercise, triglyceride concentration, body mass index
      (BMI), baseline Hb A1c, and concurrent insulin dose. RESULTS: Higher insulin
      dose, lower carbohydrate intake, and higher saturated, monounsaturated, and total
      fat intakes were associated with higher Hb A1c concentrations at year 5. In age-
      and sex-adjusted multivariate macronutrient models, substitution of fat for
      carbohydrate was associated with higher Hb A1c concentrations (P = 0.01); this
      relation remained significant after adjustment for exercise level, serum
      triglycerides, and BMI (P = 0.02) but was no longer significant (P = 0.1) after
      adjustment for baseline Hb A1c and concurrent insulin dose. CONCLUSION: Among
      intensively treated patients with type 1 diabetes, diets higher in fat and
      saturated fat and lower in carbohydrate are associated with worse glycemic
      control, independent of exercise and BMI.

PMID- 19106242
TI  - Optimization of a phytase-containing micronutrient powder with low amounts of
      highly bioavailable iron for in-home fortification of complementary foods.
AB  - BACKGROUND: In-home fortification of complementary foods with micronutrient
      powders containing low amounts of iron may be potentially safer than powders
      containing high amounts of iron. However, low iron doses have little nutritional
      effect, unless iron absorption is high. OBJECTIVE: The objective was to maximize
      iron absorption from a low-iron micronutrient powder for in-home fortification by
      testing combinations of iron as NaFeEDTA, ascorbic acid, and a microbial phytase
      active at gut pH. In addition, a recently proposed enhancer of iron absorption, L
      alpha-glycerophosphocholine (GPC), was tested. DESIGN: In 6 separate iron
      absorption studies using a crossover design, women (n = 101) consumed whole-maize
      porridge fortified with 3 mg stable isotope-labeled FeSO4 or NaFeEDTA with
      different combinations of enhancers added to the meals at the time of
      consumption. Incorporation of iron isotopes into erythrocytes 14 d later was
      measured. RESULTS: The addition of phytase when iron was present as either
      NaFeEDTA or FeSO4, with or without ascorbic acid, significantly increased iron
      absorption. The combined addition of phytase, ascorbic acid, and NaFeEDTA
      resulted in an absorption of 7.4%, compared with an absorption of 1.5% from FeSO4
      without enhancers in the same meal (P < 0.001). The addition of ascorbic acid did
      not significantly increase iron absorption from NaFeEDTA, and the addition of
      calcium did not significantly inhibit iron absorption from NaFeEDTA in the
      presence of ascorbic acid. The addition of L-alpha-glycerophosphocholine did not
      significantly increase iron absorption. CONCLUSION: Optimization of the
      micronutrient powder increased iron absorption from a highly inhibitory meal
      approximately 5-fold. This approach may allow for effective, untargeted in-home
      fortification of complementary foods with low amounts of highly bioavailable
      iron.

PMID- 19106244
TI  - Time to reconsider nonsurgical therapy of benign non-toxic multinodular goitre:
      focus on recombinant human TSH augmented radioiodine therapy.
AB  - The treatment of benign multinodular goitre (MNG) is controversial, but surgery
      is recommended in large compressive goitres. While some patients decline surgery
      others may have contraindications due to comorbidity, since MNG is prevalent in
      the elderly. Therefore, non-surgical treatment alternatives are needed. Until
      recently, levothyroxine therapy was the preferred non-surgical alternative, but
      due to low efficacy and potential side-effects, it is not recommended for routine
      use in recent international guidelines. Conventional radioiodine ((131)I) therapy
      has been used for two decades as an effective and safe alternative to surgery in
      the treatment of symptomatic non-toxic MNG. Since much higher activities of
      (131)I are employed when treating non-toxic rather than toxic MNG, there has been
      reluctance in many countries to use this treatment modality. Frequently, the
      (131)I -uptake in a non-toxic MNG is low, which makes (131)I therapy less
      feasible. Another challenge is the negative correlation between the initial
      goitre size and goitre volume reduction (GVR). With its ability to more than
      double the thyroid (131)I-uptake, recombinant human TSH (rhTSH) increases the
      absorbed radiation dose and thus enhances the GVR by 35-56% at the expense of up
      to fivefold higher rate of permanent hypothyroidism. An alternative strategy is
      to reduce the administered (131)I-activity with a factor corresponding to the
      rhTSH induced increase in (131)I-uptake. Hereby, the extrathyroidal irradiation
      can be reduced without compromising efficacy. Thus, although in its infancy, and
      still experimental, rhTSH-augmented (131)I therapy may profoundly alter the non
      surgical treatment of benign non-toxic MNG.

PMID- 19106243
TI  - Protein supplementation before and after exercise does not further augment
      skeletal muscle hypertrophy after resistance training in elderly men.
AB  - BACKGROUND: Considerable discrepancy exists in the literature on the proposed
      benefits of protein supplementation on the adaptive response of skeletal muscle
      to resistance-type exercise training in the elderly. OBJECTIVE: The objective was
      to assess the benefits of timed protein supplementation on the increase in muscle
      mass and strength during prolonged resistance-type exercise training in healthy
      elderly men who habitually consume adequate amounts of dietary protein. DESIGN:
      Healthy elderly men (n = 26) aged 72 +/- 2 y were randomly assigned to a
      progressive, 12-wk resistance-type exercise training program with (protein group)
      or without (placebo group) protein provided before and immediately after each
      exercise session (3 sessions/wk, 20 g protein/session). One-repetition maximum
      (1RM) tests were performed regularly to ensure a progressive workload during the
      intervention. Muscle hypertrophy was assessed at the whole-body (dual-energy X
      ray absorptiometry), limb (computed tomography), and muscle fiber (biopsy) level.
      RESULTS: The 1RM strength increased approximately 25-35% in both groups (P <
      0.001). Dual-energy X-ray absorptiometry and computed tomography scans showed
      similar increases in leg muscle mass (6 +/- 1% in both groups; P < 0.001) and in
      the quadriceps (9 +/- 1% in both groups), from 75.9 +/- 3.7 and 73.8 +/- 3.2 to
      82.4 +/- 3.9 and 80.0 +/- 3.0 cm2 in the placebo and protein groups, respectively
      (P < 0.001). Muscle fiber hypertrophy was greater in type II (placebo: 28 +/- 6%;
      protein: 29 +/- 4%) than in type I (placebo: 5 +/- 4%; protein: 13 +/- 6%)
      fibers, but the difference between groups was not significant. CONCLUSION: Timed
      protein supplementation immediately before and after exercise does not further
      augment the increase in skeletal muscle mass and strength after prolonged
      resistance-type exercise training in healthy elderly men who habitually consume
      adequate amounts of dietary protein. This trial was registered at
      clinicaltrials.gov as NCT00744094.

PMID- 19106245
TI  - Visceral fat mass is a strong predictor of circulating ghrelin levels in
      premenopausal women.
AB  - OBJECTIVE: A well known inverse relationship exists between obesity and
      circulating ghrelin concentrations. However, obesity is a heterogeneous disease
      entity and upper-body obesity (UBO) is associated with more profound metabolic
      disturbances than lower-body obesity (LBO). We therefore aimed to investigate the
      impact of body composition on circulating ghrelin levels in women spanning a wide
      range of body composition phenotypes. SUBJECTS AND METHODS: Ten (UBO; waist-to
      hip ratio (WHR) >0.85, body mass index (BMI) >28 kg/m(2)), ten LBO (WHR <0.80,
      BMI >28 kg/m(2)) and ten lean women (BMI<25 kg/m(2)) were studied. Total ghrelin
      levels were measured under basal and hyperinsulinemic (0.6 mU/kg per min)
      conditions. Body fat distribution was determined by dual X-ray absorptiometry in
      combination with computed tomography at the L2-L3 level. RESULTS: As expected, an
      inverse correlation existed between basal ghrelin concentration and BMI (r=-0.40,
      P=0.03) and total fat mass (r=-0.39, P=0.04). Visceral fat mass was a strong
      predictor (r=-0.56, P=0.003) of circulating ghrelin levels, even when adjusted
      for BMI (P=0.02) or body composition group (P=0.04). The suppressive effect of
      insulin on ghrelin concentration was significantly diminished in the UBO compared
      with the lean controls (P=0.012) and a highly significant inverse correlation
      existed with visceral fat mass (r=-0.52, P=0.004). CONCLUSIONS: Visceral fat mass
      is a strong predictor of basal ghrelin concentrations and also attenuates the
      suppressive effect of insulin on ghrelin concentrations. These data provide
      further evidence that the UBO phenotype is associated with more profound
      metabolic abnormalities than obesity per se.

PMID- 19106246
TI  - Fat for life: new stories on old grease.

PMID- 19106247
TI  - Adipose triglyceride lipase in human skeletal muscle is upregulated by exercise
      training.
AB  - Mobilization of fatty acids from stored triacylglycerol (TG) in adipose tissue
      and skeletal muscle [intramyocellular triacylglycerol (IMTG)] requires activity
      of lipases. Although exercise training increases the lipolytic capacity of
      skeletal muscle, the expression of hormone-sensitive lipase (HSL) is not changed.
      Recently, adipose triglyceride lipase (ATGL) was identified as a TG-specific
      lipase in various rodent tissues. To investigate whether human skeletal muscle
      ATGL protein is regulated by endurance exercise training, 10 healthy young men
      completed 8 wk of supervised endurance exercise training. Western blotting
      analysis on lysates of skeletal muscle biopsy samples revealed that exercise
      training induced a twofold increase in skeletal muscle ATGL protein content. In
      contrast to ATGL, expression of comparative gene identification 58 (CGI-58), the
      activating protein of ATGL, and HSL protein was not significantly changed after
      the training period. The IMTG concentration was significantly decreased by 28% at
      termination of the training program compared with before. HSL-phoshorylation at
      Ser(660) was increased, HSL-Ser(659) phosporylation was unchanged, and HSL
      phoshorylation at Ser(565) was decreased altogether, indicating an enhanced basal
      activity of this lipase. No change was found in the expression of diacylglycerol
      acyl transferase 1 (DGAT1) after training. Inhibition of HSL with a monospecific,
      small molecule inhibitor (76-0079) and stimulation of ATGL with CGI-58 revealed
      that significant ATGL activity is present in human skeletal muscle. These results
      suggest that ATGL in addition to HSL may be important for human skeletal muscle
      lipolysis.

PMID- 19106248
TI  - ALCAT1 is a polyglycerophospholipid acyltransferase potently regulated by adenine
      nucleotide and thyroid status.
AB  - Acyl-CoA:lysocardiolipin acyltransferase-1 (ALCAT1) catalyzes acylation of
      lysocardiolipin back to cardiolipin, an important step in cardiolipin remodeling.
      The present study reports the catalytic properties of ALCAT1 in vitro and its
      regulation by thyroid hormone status in mouse liver and heart. Recombinant ALCAT1
      expressed in Sf9 cells preferred basic pH conditions and did not require divalent
      cations or integrity of the subcellular membrane for its enzymatic activity.
      Recombinant ALCAT1 was potently inhibited by ADP and ATP, but not by adenosine
      nucleotide analogs or other nucleotides, such as UTP and GTP, suggesting that
      ALCAT1 does not require ATP hydrolysis for its enzyme activity. In addition to
      cardiolipin, ALCAT1 also catalyzed acylation of other members of the
      polyglycerophospholipid family, including phosphatidylglycerol, a precursor for
      cardiolipin synthesis, and bis(monoacylglycero)phosphate, a structural isomer of
      lysophosphatidylglycerol and a metabolic intermediate of cardiolipin. These
      findings suggest that ALCAT1 plays a role in the remodeling of other
      polyglycerophospholipids. In support of a regulatory role of ALCAT1 in
      cardiolipin remodeling in response to oxidative stress, ALCAT1 expression in
      liver and heart was significantly downregulated in mice with hypothyroidism and
      upregulated in mice treated with thyroid hormone, which is known to stimulate
      mitochondrial activity, oxidative stress, and cardiolipin remodeling.

PMID- 19106249
TI  - Incretin release from gut is acutely enhanced by sugar but not by sweeteners in
      vivo.
AB  - Glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1
      (GLP-1) are released during meals from endocrine cells located in the gut mucosa
      and stimulate insulin secretion from pancreatic beta-cells in a glucose-dependent
      manner. Although the gut epithelium senses luminal sugars, the mechanism of sugar
      sensing and its downstream events coupled to the release of the incretin hormones
      are not clearly elucidated. Recently, it was reported that sucralose, a sweetener
      that activates the sweet receptors of taste buds, triggers incretin release from
      a murine enteroendocrine cell line in vitro. We confirmed that immunoreactivity
      of alpha-gustducin, a key G-coupled protein involved in taste sensing, is
      sometimes colocalized with GIP in rat duodenum. We investigated whether secretion
      of incretins in response to carbohydrates is mediated via taste receptors by
      feeding rats the sweet-tasting compounds saccharin, acesulfame potassium, d
      tryptophan, sucralose, or stevia. Oral gavage of these sweeteners did not reduce
      the blood glucose excursion to a subsequent intraperitoneal glucose tolerance
      test. Neither oral sucralose nor oral stevia reduced blood glucose levels in
      Zucker diabetic fatty rats. Finally, whereas oral glucose increased plasma GIP
      levels approximately 4-fold and GLP-1 levels approximately 2.5-fold
      postadministration, none of the sweeteners tested significantly increased levels
      of these incretins. Collectively, our findings do not support the concept that
      release of incretins from enteroendocrine cells is triggered by carbohydrates via
      a pathway identical to the sensation of "sweet taste" in the tongue.

PMID- 19106250
TI  - Effects of prolonged fasting and sustained lipolysis on insulin secretion and
      insulin sensitivity in normal subjects.
AB  - Normal beta-cells adjust their function to compensate for any decrease in insulin
      sensitivity. Our aim was to explore whether a prolonged fast would allow a study
      of the effects of changes in circulating free fatty acid (FFA) levels on insulin
      secretion and insulin sensitivity and whether any potential effects could be
      reversed by the antilipolytic agent acipimox. Fourteen (8 female, 6 male) healthy
      young adults (aged 22.8-26.9 yr) without a family history of diabetes and a body
      mass index of 22.6 +/- 3.2 kg/m(2) were studied on three occasions in random
      order. Growth hormone and FFA levels were regularly measured overnight (2200
      0759), and subjects underwent an intravenous glucose tolerance test in the
      morning (0800-1100) on each visit. Treatment A was an overnight fast, treatment B
      was a 24-h fast with regular administrations of a placebo, and treatment C was a
      24-h fast with regular ingestions of 250 mg of acipimox. The 24-h fast increased
      overnight FFA levels (as measured by the area under the curve) 2.8-fold [51.3
      (45.6-56.9) vs. 18.4 (14.4-22.5) *10(4) micromol/l*min, P < 0.0001], and it led
      to decreases in insulin sensitivity [5.7 (3.6-8.9) vs. 2.6 (1.3-4.7) *10(-4) min(
      1) per mU/l, P < 0.0001] and the acute insulin response [16.3 (10.9-21.6) vs.
      12.7 (8.7-16.6) *10(2) pmol/l*min, P = 0.02], and therefore a reduction in the
      disposition index [93.1 (64.8-121.4) vs. 35.5 (21.6-49.4) *10(2) pmol/mU, P <
      0.0001]. Administration of acipimox during the 24-h fast lowered FFA levels by an
      average of 20% (range: -62 to +49%; P = 0.03), resulting in a mean increase in
      the disposition index of 31% (P = 0.03). In conclusion, the 24-h fast was
      accompanied by substantial increases in fasting FFA levels and induced reductions
      in the acute glucose-simulated insulin response and insulin sensitivity. The use
      of acipimox during the prolonged fast increased the disposition index, suggesting
      a partial reversal of the effects of fasting on the acute insulin response and
      insulin sensitivity.

PMID- 19106251
TI  - A multisite description of juvenile drug courts: program models and during
      program outcomes.
AB  - Like adult drug courts, juvenile drug courts have proliferated at a rapid rate
      during the past 15 years, but comparatively little research has been conducted on
      them. Although a few studies indicate that these programs appear to show promise
      as an intervention, almost nothing has been published using systematic and
      empirical methods to provide a description and specific examples of how these
      programs are structured and implemented. The purpose of the current study,
      therefore, is to summarize and integrate findings from systematic process
      evaluations of three juvenile drug courts. Similarities and differences in the
      structure and design of the programs are noted and findings regarding the program
      model for each juvenile drug court, including target population, therapeutic
      activities, and initial and long-term goals are presented. During-program outcome
      data also are presented, and findings are reported as a "snapshot" of what
      happened during one calendar year in the operation of each program.

PMID- 19106252
TI  - Botulinum toxin-a in children with congenital spastic hemiplegia does not improve
      upper extremity motor-related function over rehabilitation alone: a randomized
      controlled trial.
AB  - BACKGROUND: Rehabilitation of the upper extremity in children with hemiplegic
      cerebral palsy has not been compared to the same intensity of therapy combined
      with injected botulinum toxin (BTX). OBJECTIVE: To measure the short-term (2
      weeks) and long-term (6 and 9 months) effects of a standardized functional
      training program versus without the addition of chemodenervation of forearm and
      hand muscles. METHODS: Twenty children with spastic hemiplegia, aged 4 to 16
      years, were matched for baseline characteristics and then randomized to
      standardized functional physical and occupational therapies for 6 months (PT/OT
      group) or to the same therapies plus multimuscle BTX-A (BTX+ group). MAIN OUTCOME
      MEASURES: were isometric generated force, overshoot and undershoot (force
      production error), active and passive range of motion by goniometry (ROM),
      stretch restricted angle (SRA) of joints, Ashworth scores at the elbow and wrist,
      and the Melbourne assessment of unilateral upper limb function. All measures were
      performed at baseline, 2 weeks after BTX-A, 6 months (end of therapy), and then 3
      months after termination of the therapy. RESULTS: Clinical measures (muscle tone,
      active ROM of wrist and elbow) showed improvement in both groups. However, no
      significant differences emerged between groups on functional measures. Generated
      force decreased directly after the BTX-A injection but increased during the
      therapy period. The PT/OT group, however, showed a significantly higher increase
      in force and accuracy with therapy compared with the BTX+ therapy group.
      CONCLUSIONS: Functional rehabilitation therapies for the upper extremity increase
      manual isometric flexor force at the wrist and ROM, but BTX injections cause
      weakness and do not lead to better outcomes than therapy alone.

PMID- 19106253
TI  - Restoring continence in frail older people living in the community: what factors
      influence successful treatment outcomes?

PMID- 19106254
TI  - Analysis of recurrent events: a systematic review of randomised controlled trials
      of interventions to prevent falls.
AB  - RATIONALE: there are several well-developed statistical methods for analysing
      recurrent events. Although there are guidelines for reporting the design and
      methodology of randomised controlled trials (RCTs), analysis guidelines do not
      exist to guide the analysis for RCTs with recurrent events. Application of
      statistical methods that do not account for recurrent events may provide
      erroneous results when used to test the efficacy of an intervention. It is
      unknown what proportion of RCTs of falls prevention studies have utilised
      statistical methods that incorporate recurrent events. METHODS: we conducted a
      systematic review of RCTs of interventions to prevent falls in community-dwelling
      older persons. We searched Medline from 1994 to November 2006. We determined the
      proportion of studies that reported using three statistical methods appropriate
      for the analysis of recurrent events (negative binomial regression, Andersen-Gill
      extension of the Cox model and the WLW marginal model). RESULTS: fewer than one
      third of 83 papers that reported falls as an outcome utilised any appropriate
      statistical method (negative binomial regression, Andersen-Gill extension of the
      Cox model and Cox marginal model) to analyse recurrent events and fewer than 15%
      utilised graphical methods to represent falls data. CONCLUSION: RCTs that have a
      recurrent event end-point should include an analysis appropriate for recurrent
      event data such as negative binomial regression, Andersen-Gill extension of the
      Cox model and/or the WLW marginal model. We recommend that researchers and
      clinicians seek consultation with a statistician with expertise in recurrent
      event methodology.

PMID- 19106255
TI  - Advancing age is not a reason to withhold ERCP.

PMID- 19106256
TI  - Predicting the impact of the screening programme for colorectal cancer in the UK.
AB  - OBJECTIVES: Screening for colorectal cancer by biennial testing for faecal occult
      blood is being introduced in the UK from 2007. We examine the likely impact of
      the programme, in terms of reduced mortality, lives saved and changes in
      incidence, over the next 20 years. SETTING: Projections of incidence and
      mortality of colorectal cancer in England, and the policy that has been adopted
      for screening in England (biennial at ages 60-69 from 2007, then 60-74 in 2010).
      METHODS: The results are based on the output of a simulation model that has been
      used to examine cost-effectiveness of screening policy options, with two
      scenarios regarding compliance with screening; both assume that 20% of the
      population will never attend for screening, but attendance of those who do is
      modelled either as a random 60% or 80%, at each screening round. RESULTS: The
      decrease in mortality rates expected 20 years after introducing screening is 13
      17% in men and 12-15% in women (depending on the attendance levels). The model
      predicts an initial rise in incidence, followed (after six to seven years) by a
      fall, so that there is little net change in the number of cases detected over a
      20-year period. CONCLUSION: Percentage changes in mortality seem modest, but the
      projected saving in terms of numbers of lives is not negligible--1800-2400 per
      year by 2025 in England (equivalent numbers are 2200-2700 in all over the UK).
      Newer screening modalities may improve on these projected results.

PMID- 19106257
TI  - Cost evaluation in a colorectal cancer screening programme by faecal occult blood
      test in the District of Florence.
AB  - OBJECTIVES: To evaluate the direct costs of first and repeat colorectal cancer
      screening by immunochemical faecal occult blood testing (I-FOBT). METHODS:
      Florence district residents aged 50-70 were invited to undergo one-time I-FOBT
      every two years. Full colonoscopy was recommended for FOBT-positive subjects.
      Direct cost analysis was carried out separately for the first and repeat
      screening. All relevant resources consumed by the programme were calculated.
      RESULTS: Among 25,428 or 62,369 subjects invited to the first or repeat
      screening, respectively, the corresponding participation rate was 47.8% or 52.3%,
      and the positivity rate was 4.4% and 3.3%. Corresponding detection rates and
      positive predictive values for cancer and advanced adenoma were 11.3% or 8.9% and
      32.4% or 32.8%, respectively. The assessment phase accounted for the major cost,
      as compared with recruitment and screening. All cost indicators were slightly
      higher in the first screening compared with repeat screening. Cost per cancer and
      advanced adenoma detected was similar in the first or repeat screening. A higher
      than observed participation rate would have substantially reduced screening cost.
      CONCLUSION: Analysis of I-FOBT-organized population-based screening cost
      demonstrates lower cost at repeat compared with first screening and provides
      reference for decision-making in screening implementation.

PMID- 19106258
TI  - Impact of changing from annual to biennial mammographic screening on breast
      cancer outcomes in women aged 50-79 in British Columbia.
AB  - OBJECTIVES: The objective of this study was to compare breast cancer outcomes
      among women subject to different policies on mammography screening frequency.
      SETTING: Data were obtained for women participating in the Screening Mammography
      Programme of British Columbia (SMPBC) for 1988--2005. The SMPBC changed its
      policy for women aged 50-79 years from annual to biennial mammography in 1997,
      but retained an annual recommendation for women aged 40-49 years. METHODS: Breast
      cancer outcomes were compared for women participating in the programme before and
      after 1997 for two groups: ages 40-49 and 50-79 years. RESULTS: There were data
      on 658,151 women. Comparing pre-1997 and post-1997, the median interscreen
      interval increased by 11.1 months in women 50-79 but by only 0.3 months in women
      aged 40-49. Excluding those detected at initial screen, 6291 breast cancers were
      identified. Comparing pre-1997 and post-1997: the relative rates (RR) of screen
      detected cancer increased in women aged 40-49 (RR = 1.32) and the rate of
      invasive cancers > or =20 mm at diagnosis decreased (RR = 0.83); the rate of
      cancers with axillary node involvement increased in women aged 50-79 (RR = 1.23).
      Cancer survival improved after 1997 for women diagnosed at ages 40-49 (hazard
      ratio = 0.62), but was unchanged for women aged 50-79. Breast cancer mortality
      rates did not change between the periods in either age group. CONCLUSION: The
      proximal cancer outcomes considered (staging and survival) improved in women aged
      40-49 but this was offset in women aged 50-79 associated with the change in
      screen frequency. These changes did not result in alterations in breast cancer
      mortality rates in either age group.

PMID- 19106259
TI  - Normal endometrial cells in cervical cytology: systematic review of prevalence
      and relation to significant endometrial pathology.
AB  - OBJECTIVES: To estimate the prevalence of normal endometrial cells (NECs) and the
      proportion of NECs associated with significant endometrial pathology in
      conventional and liquid-based cytology (LBC) cervical smears; and to assess the
      association between NECs and clinical symptoms in women with endometrial
      hyperplasia or carcinoma. METHODS: Systematic review of the literature and meta
      analysis of prevalence and proportion data. The review was confined to studies
      reporting on NECs in smears from postmenopausal women or women aged 40+. RESULTS:
      A total of 22 relevant primary studies were identified from 1970 to 2007. The
      overall summary estimate for the prevalence of NECs in smears from postmenopausal
      women or women aged 40+ in all screening smears was 0.4% (95% CI 0.2-0.7%); this
      was 0.3% (95% CI 0.1-0.5%) and 0.9% (95% CI 0.5-1.4%) for conventional and LBC
      smears, respectively; P = 0.003 for difference. The overall estimate for the
      proportion of NECs associated with significant endometrial pathology was 7% (95%
      CI 4-10%); this was 11% (95% CI 8-14%) and 2% (95% CI 1-2%) for conventional and
      LBC smears, respectively; P < 0.001 for difference. In women with significant
      endometrial pathology, the presence of NECs in followed-up women was associated
      with abnormal uterine bleeding in 79% (95% CI 68-87%) of cases. CONCLUSION:
      Compared with conventional cytology, LBC may be associated with a higher
      prevalence of NECs but these are less likely to be associated with endometrial
      pathology. This finding might be explained by more consistent use of sampling
      instruments for LBC with better access to the endocervical canal or alternatively
      by changes over time, broadly coincident with the introduction of LBC, in the
      population in which NECs are reported. In followed-up women with NECs, most
      endometrial pathology is accompanied by symptoms, implying that a relatively
      smaller number of additional cases are identified through follow-up of
      asymptomatic women.

PMID- 19106260
TI  - Automated imaging of circulating fluorocytes for the diagnosis of erythropoietic
      protoporphyria: a pilot study for population screening.
AB  - OBJECTIVES: To improve the traditional fresh blood film method to a high
      throughput analysis of the presence of circulating fluorescent red cells
      (fluorocytes) in erythropoietic protoporphyria (EPP) using an automated imaging
      system. METHODS: Based on the autofluorescence of protoporphyrin, we used an
      automatic image acquisition platform for examining fluorocytes in peripheral
      blood with minimal sample preparation. The image acquisition is easy-to-use under
      automated operations of excitation, focusing, detection and data analysis.
      Quality image and semi-quantitative fluorescence measurement of fluorocytes can
      be generated in a single step. For high-throughput analysis, the platform can
      image more than 200 96-well micro-plates, i.e. 19200 samples, in approximately 10
      hours. Importantly, the reagent cost of analysis is negligible. RESULTS: In this
      pilot study, three EPP patients were diagnosed and 4000 normal individuals were
      screened for EPP by this method. Our results showed that the method can
      distinguish the overt case and asymptomatic carriers. It gives reliable evidence
      for rapid EPP screening. CONCLUSION: This automated imaging system provides
      multiple advantages that improve the traditional fresh blood film method as a
      more effective diagnostic tool and facilitates population screening for EPP. As
      fluorocytes are present in the umbilical cord blood of EPP patients, this high
      throughput method can be potentially used for newborn screening of EPP.

PMID- 19106261
TI  - First trimester Down's syndrome screening marker values and cigarette smoking:
      new data and a meta-analysis on free beta human chorionic gonadotophin, pregnancy
      associated plasma protein-A and nuchal translucency.
AB  - OBJECTIVES: To examine the effect of smoking on three first trimester screening
      markers for Down's syndrome that constitute the Combined test, namely nuchal
      translucency (NT), pregnancy-associated plasma protein-A (PAPP-A) and free beta
      human chorionic gonadotophin (free beta-hCG) and to use the results to determine
      which of these markers need to be adjusted for smoking and by how much. METHODS:
      The difference in the median multiple of the median (MoM) values in smokers
      compared to non-smokers was determined for NT, PAPP-A and free beta-hCG in 12,517
      unaffected pregnancies that had routine first trimester Combined test screening.
      These results were then included in a meta-analysis of published studies and the
      effect of adjusting for smoking on screening performance of the Combined test was
      estimated. RESULTS: The results using the routine screening data were similar to
      the summary estimates from the meta-analysis of all studies. The results from the
      meta-analysis were; median MoM in smokers compared to non-smokers: 1.06 NT (95%
      confidence interval 1.03 to 1.10), 0.81 PAPP-A (0.80 to 0.83) and 0.94 free beta
      hCG (0.89 to 0.99). The effect of adjusting for smoking on the Combined test is
      small, with an estimated less than half percentage point increase in the
      detection rate (the proportion of affected pregnancies with a positive result)
      for a 3% false-positive rate (the proportion of unaffected pregnancies with a
      positive result) and less than 0.2 percentage point decrease in the false
      positive rate for an 85% detection rate. CONCLUSION: Adjusting first trimester
      screening markers for smoking has a minimal favourable effect on screening
      performance, but it is simple to implement and this paper provides the adjustment
      factors needed if a decision is made to make such an adjustment.

PMID- 19106262
TI  - Consensus recommendations for cervical cancer prevention in the Czech Republic: a
      report of the International Conference on Human Papillomavirus in Human Pathology
      (Prague, 1-3 May 2008).
AB  - A comparison of cervical cancer incidence and mortality in the Czech Republic
      with that from other countries shows that the burden of cervical cancer here is
      considerably higher than in Western Europe, where screening is widespread. In May
      2008, the International Conference on Human Papillomavirus in Human Pathology was
      convened to review the latest evidence and to formulate consensus recommendations
      for the reduction of cervical cancer rates. The Czech Republic is spending
      considerable resources on cervical cancer prevention, but these resources are
      being used inefficiently. The current system is characterized by a lack of
      coordination and monitoring that leads to the over-screening of a minority of
      women while the majority of the target population are under-screened or not
      screened at all. It was recommended that a comprehensive, organized programme be
      implemented, coordinated by an independent administrative body with legal and
      budgetary responsibility. As the laboratory infrastructure and professional
      technical skills required for a quality-assured organized screening programme are
      already in place, implementation of this programme would not require much in the
      way of additional resources to produce substantial cost-effective reductions in
      cervical cancer rates.

PMID- 19106263
TI  - Audit of subjects with family history of colorectal cancer attending a familial
      cancer service.

PMID- 19106264
TI  - The cost of screening for gestational diabetes mellitus.

PMID- 19106265
TI  - Accuracy of three-dimensional measurements obtained from cone beam computed
      tomography surface-rendered images for cephalometric analysis: influence of
      patient scanning position.
AB  - The aims of this study were to assess the accuracy of linear measurements on
      three-dimensional (3D) surface-rendered images generated from cone beam computed
      tomography (CBCT) in comparison with two-dimensional (2D) slices and 2D lateral
      and postero-anterior (PA) cephalometric projections, and to investigate the
      influence of patient head position in the scanner on measurement accuracy. Eight
      dry human skulls were scanned twice using NewTom 3G CBCT in an ideal and a
      rotated position and the resulting datasets were used to create 3D surface
      rendered images, 2D tomographic slices, and 2D lateral and PA projections. Ten
      linear distances were defined for cephalometric measurements. The physical and
      radiographic measurements were repeated twice by three independent observers and
      were compared using repeated measures analysis of variance (P=0.05). The
      radiographic measurements were also compared between the ideal and the rotated
      scan positions. The radiographic measurements of the 3D images were closer to the
      physical measurements than the 2D slices and 2D projection images. No
      statistically significant difference was found between the ideal and the rotated
      scan measurements for the 3D images and the 2D tomographic slices. A
      statistically significant difference (P<0.001) was observed between the ideal and
      rotated scan positions for the 2D projection images. The findings indicate that
      measurements based on 3D CBCT surface images are accurate and that small
      variations in the patient's head position do not influence measurement accuracy.

PMID- 19106266
TI  - Recombinant human thyrotropin enhances endothelial-mediated vasodilation of
      conduit arteries.
AB  - CONTEXT: Endothelial cells possess receptors to TSH. Their role is largely
      unknown. OBJECTIVES: The objective of the study was to determine whether elevated
      serum TSH levels, as occur in hypothyroidism, affect endothelial function of
      large arteries and vascular risk biomarkers. SUBJECTS AND METHODS: Thirty-four
      consecutively recruited patients, who had undergone thyroidectomy for thyroid
      carcinoma, were studied in connection with one of the monitoring procedures based
      on recombinant human (rh) TSH administration. Flow-mediated dilation (FMD) of the
      brachial artery and serum vascular risk markers were measured at baseline and for
      5 d after the administration of rhTSH (0.9 mg im on d 1 and 2). Holter
      electrocardiogram and echocardiography were performed on d 2. RESULTS: rhTSH
      caused a rapid increase in flow-mediated dilation from the basal value of 10.2 to
      15.6% at 6 h (P < 0.0000001), to 16.1% on d 2 (P < 0.0000001), and to 14.9% on d
      6 (P = 0.0015). The results were identical when the analysis was made in a
      subgroup of 19 patients free of vascular risk conditions. Vascular cell adhesion
      molecule-1, TNFalpha, IL-6, and high sensitive C-reactive protein were unaffected
      by rhTSH, whereas homocysteine was decreased. Arterial blood pressure, mean 24-h
      heart rate, and left ventricular function were unaffected by rhTSH. CONCLUSIONS:
      rhTSH causes marked and persistent activation of the endothelial mediated
      vasodilation, independent of systemic hemodynamic changes.

PMID- 19106267
TI  - A screening study of thyroid cancer and other thyroid diseases among individuals
      exposed in utero to iodine-131 from Chernobyl fallout.
AB  - BACKGROUND: Like stable iodine, radioiodines concentrate in the thyroid gland,
      increasing thyroid cancer risk in exposed children. Data on exposure to the
      embryonic/fetal thyroid are rare, raising questions about use of iodine 131 (I
      131) in pregnant women. We present here estimated risks of thyroid disease from
      exposure in utero to I-131 fallout from the Chernobyl nuclear accident. METHODS:
      We conducted a cross-sectional thyroid screening study (palpation, ultrasound,
      thyroid hormones, and, if indicated, fine needle aspiration) from 2003 to 2006.
      Participants were 2582 mother-child pairs from Ukraine in which the mother had
      been pregnant at the time of the accident on April 26, 1986, or 2 months after
      the time during which I-131 fallout was still present (1494 from contaminated
      areas, 1088 in the comparison group). Individual cumulative in utero thyroid dose
      estimates were derived from estimated I-131 activity in the mother's thyroid
      (mean 72 mGy; range 0-3230 mGy). RESULTS: There were seven cases of thyroid
      carcinoma and one case of Hurthle cell neoplasm identified as a result of the
      screening. Whereas the estimated excess odds ratio per gray for thyroid carcinoma
      was elevated (excess odds ratio per gray 11.66), it was not statistically
      significant (P = 0.12). No radiation risks were identified for other thyroid
      diseases. CONCLUSION: Our results suggest that in utero exposure to radioiodines
      may have increased the risk of thyroid carcinoma approximately 20 yr after the
      Chernobyl accident, supporting a conservative approach to medical uses of I-131
      during pregnancy.

PMID- 19106268
TI  - Associations of serum adiponectin with skeletal muscle morphology and insulin
      sensitivity.
AB  - CONTEXT: Skeletal muscle morphology and function are strongly associated with
      insulin sensitivity. OBJECTIVE: The objective of the study was to test the
      hypothesis that circulating adiponectin is associated with skeletal muscle
      morphology and that adiponectin mediates the relation of muscle morphology to
      insulin sensitivity. DESIGN, SETTINGS, AND PARTICIPANTS: This was a cross
      sectional investigation of 461 men aged 71 yr, participants of the community
      based Uppsala Longitudinal Study of Adult Men study. MAIN OUTCOME MEASURES:
      Measures included serum adiponectin, insulin sensitivity measured with euglycemic
      insulin clamp technique, and capillary density and muscle fiber composition
      determined from vastus lateralis muscle biopsies. RESULTS: In multivariable
      linear regression models (adjusting for age, physical activity, fasting glucose,
      and pharmacological treatment for diabetes), serum adiponectin levels rose with
      increasing capillary density (beta, 0.30 per 50 capillaries per square millimeter
      increase; P = 0.041) and higher proportion of type I muscle fibers (beta, 0.27
      per 10% increase; P = 0.036) but declined with a higher proportion of type IIb
      fibers (beta, -0.39 per 10% increase; P = 0.014). Using bootstrap methods to
      examine the potential role of adiponectin in associations between muscle
      morphology and insulin sensitivity and the associations of capillary density
      (beta difference, 0.041; 95% confidence interval 0.001, 0.085) and proportion of
      type IIb muscle fibers (beta difference, -0.053; 95% confidence interval -0.107, 
      0.002) with insulin sensitivity were significantly attenuated when adiponectin
      was included in the models. CONCLUSIONS: Circulating adiponectin concentrations
      were higher with increasing skeletal muscle capillary density and in individuals
      with higher proportion of slow oxidative muscle fibers. Furthermore, our results
      indicate that adiponectin could be a partial mediator of the relations between
      skeletal muscle morphology and insulin sensitivity.

PMID- 19106269
TI  - Long-term effects of Roux-en-Y gastric bypass surgery on plasma glucagon-like
      peptide-1 and islet function in morbidly obese subjects.
AB  - CONTEXT: An enlarged incretin response after Roux-en-Y gastric bypass (RYGBP) has
      been proposed to promote excessive beta-cell function and mass. OBJECTIVE: The
      objective of the study was to determine whether RYGBP is associated with a
      steadily increased glucagon-like peptide 1 (GLP-1) response and a disruption of
      the relationship between insulin sensitivity and insulin secretion required to
      maintain plasma glucose in the normal range. DESIGN AND PATIENTS: This was a
      cross-sectional study. Twenty-four women divided into three groups according to
      time after RYGBP (9-15, 21-30, and more than 36 months). Eight normal-weight and
      eight morbidly obese women served as controls. MAIN OUTCOME MEASURES: GLP-1 was
      determined after a standardized test meal. Insulin secretion (AIRg) and insulin
      sensitivity (S(I)) were derived from an iv glucose tolerance test. Postprandial
      glucose profile was recorded with a continuous glucose monitoring system.
      RESULTS: Area under the curve(0-120) of GLP-1 was larger after RYGBP compared
      with controls (P < 0.01) but was comparable among surgical groups (P =0.314).
      Time after surgery was not associated with changes in S(I) (P = 0.657), AIRg (P =
      0.329), or the disposition index (DI = AIRgS(I), P = 0.915). After surgery, the
      GLP-1 response and the DI were not significantly correlated (P = 0.304). Glucose
      less than 50 mg/dl was found in operated subjects, but the proportion did not
      increase with time after surgery (P = 0.459). Neither the GLP-1 response (P =
      0.620) nor the DI (P = 0.457) differed significantly between those with or
      without hypoglycemic episodes. CONCLUSIONS: Although the GLP-1 response to meal
      intake is steadily elevated after RYGBP, this does not result over time in the
      development of an inappropriate insulin secretion relative to the prevailing
      insulin sensitivity or the occurrence of hypoglycemic episodes.

PMID- 19106270
TI  - Genetic association between the interleukin-2 receptor-alpha gene and mode of
      onset of type 1 diabetes in the Japanese population.
AB  - CONTEXT/OBJECTIVE: The IL-2 receptor-alpha (IL2RA), also known as CD25, is
      expressed on the regulatory T cells, which play an important role in the control
      of immune responses and the maintenance of immune homeostasis. Our objective was
      to determine whether variants in the IL2RA gene are associated with type 1
      diabetes in the Japanese population. DESIGN/PATIENTS: We genotyped the four
      single-nucleotide polymorphisms (rs706778, rs3118470, ss52580101, and rs11594656)
      of the IL2RA in 885 patients with type 1 diabetes and 606 control subjects of
      Japanese origin. The allele and genotype frequencies were examined in the patient
      groups stratified by their mode of onset in a case-control study. RESULTS: We
      found evidence of association with acute-onset, but not slow-onset and fulminant,
      type 1 diabetes for two of the four single-nucleotide polymorphisms genotyped
      (rs706778 and rs3118470). The rs706778 A allele and the rs3118470 G allele were
      associated with an increased disease risk [odds ratio (OR) for rs706778 AA
      genotype 1.54, P = 4.2 x 10(-4) and OR for rs3118470 GG genotype 1.50, P =
      0.0019, respectively]. Furthermore, the A-G haplotype was associated with
      increased type 1 diabetes risk in the acute-onset form (OR 1.30, P = 0.002).
      CONCLUSIONS: The present data confirm the type 1 diabetes association with IL2RA
      and provide evidence that the different contributions of the IL2RA in the
      susceptibility to acute-onset and other forms of type 1 diabetes in the Japanese
      population.

PMID- 19106271
TI  - Perinatal outcome of children born to mothers with thyroid dysfunction or
      antibodies: a prospective population-based cohort study.
AB  - CONTEXT: There are only a few large prospective studies involving evaluation of
      the effect of maternal thyroid dysfunction on offspring and observations are
      inconsistent. OBJECTIVE: The objective of the study was to investigate the
      effects of thyroid dysfunction or antibody positivity on perinatal outcome.
      SETTING AND PARTICIPANTS: The study included prospective population-based
      Northern Finland Birth Cohort 1986 including 9247 singleton pregnancies. First
      trimester maternal serum samples were analyzed for thyroid hormones [TSH, free
      T(4) (fT4)] and antibodies [thyroid-peroxidase antibody (TPO-Ab) and
      thyroglobulin antibody (TG-Ab)]. Mothers were classified by their hormone and
      antibody status into percentile categories based on laboratory data and compared
      accordingly. MAIN OUTCOMES: Outcomes were perinatal mortality, preterm delivery,
      absolute and gestational age-adjusted birth weight, and absolute and relative
      placental weight. RESULTS: The offspring of TPO-Ab- and TG-Ab-positive mothers
      had higher perinatal mortality, which was not affected by thyroid hormone status.
      Unadjusted and adjusted (for maternal age and parity) risk for increased
      perinatal mortality was an odds ratio of 3.1 (95% confidence interval 1.4-7.1)
      and 3.2 (1.4-7.1) in TPO-Ab- and 2.6 (1.1-6.2) and 2.5 (1.1-5.9) in TG-Ab
      positive mothers. TPO-Ab-positive mothers had more large-for-gestational age
      infants (2.4 vs. 0.8%, P = 0.017), as did mothers with low TSH and high fT4
      concentrations vs. reference group (6.6 vs. 2.5%, P = 0.045). Significantly
      higher placental weights were observed among mothers with low TSH and high fT4 or
      high TSH and low fT4 levels as well as among TPO-Ab-positive mothers.
      CONCLUSIONS: First-trimester antibody positivity is a risk factor for perinatal
      death but not thyroid hormone status as such. Thyroid dysfunction early in
      pregnancy seems to affect fetal and placental growth.

PMID- 19106272
TI  - Association between vitamin D deficiency and primary cesarean section.
AB  - BACKGROUND: At the turn of the 20th century, women commonly died in childbirth
      due to rachitic pelvis. Although rickets virtually disappeared with the discovery
      of the hormone vitamin D, recent reports suggest vitamin D deficiency is
      widespread in industrialized nations. Poor muscular performance is an established
      symptom of vitamin D deficiency. The current U.S. cesarean birth rate is at an
      all-time high of 30.2%. We analyzed the relationship between maternal serum 25
      hydroxyvitamin D [25(OH)D] status, and prevalence of primary cesarean section.
      METHODS: Between 2005 and 2007, we measured maternal and infant serum 25(OH)D at
      birth and abstracted demographic and medical data from the maternal medical
      record at an urban teaching hospital (Boston, MA) with 2500 births per year. We
      enrolled 253 women, of whom 43 (17%) had a primary cesarean. RESULTS: There was
      an inverse association with having a cesarean section and serum 25(OH)D levels.
      We found that 28% of women with serum 25(OH)D less than 37.5 nmol/liter had a
      cesarean section, compared with only 14% of women with 25(OH)D 37.5nmol/liter or
      greater (P = 0.012). In multivariable logistic regression analysis controlling
      for race, age, education level, insurance status, and alcohol use, women with
      25(OH)D less than 37.5 nmol/liter were almost 4 times as likely to have a
      cesarean than women with 25(OH)D 37.5 nmol/liter or greater (adjusted odds ratio
      3.84; 95% confidence interval 1.71 to 8.62). CONCLUSION: Vitamin D deficiency was
      associated with increased odds of primary cesarean section.

PMID- 19106273
TI  - Relation between serum testosterone, serum estradiol, sex hormone-binding
      globulin, and geometrical measures of adult male proximal femur strength.
AB  - CONTEXT: Although previous studies have indicated associations between
      circulating testosterone (T) or estradiol (E2) concentrations and bone mineral
      density, the relationship between gonadal steroids and skeletal geometry is not
      well defined. OBJECTIVE: Our objective was to uncover the relation between
      circulating T or E2 and proximal femur geometry in a diverse sample of men.
      DESIGN: We used data on 808 men enrolled in the Boston Area Community Health/Bone
      Study. Serum concentrations of total and calculated free T and E2 were obtained
      via early-morning blood sampling. The geometry of the proximal femur at three
      sites (the narrow neck, intertrochanter, and shaft) was obtained using the Hip
      Structural Analysis technology. Analyses adjusted for subjects' age, height,
      total body lean mass and fat mass, and level of physical activity were performed.
      SETTING: In-home interviews accompanied by subject visits to the General Clinical
      Research Center at Boston University School of Medicine were performed. STUDY
      PARTICIPANTS: A randomly selected cohort of men living in Boston, MA (ages 30-79
      yr) was included in the study. INTERVENTIONS: These were not applicable. MAIN
      OUTCOME MEASURES: Bone mineral density and bone outer diameter, cross-sectional
      area (measuring bone material), and section modulus (an index of bending
      strength) were calculated. RESULTS: In age-adjusted models, E2 was positively
      associated with hip strength parameters, whereas T was not. Adjustment for age
      and other parameters resulted in substantial reductions in, but not complete
      elimination of, associations between E2 and hip strength parameters. CONCLUSION:
      Circulating E2 is strongly associated with proximal femur strength, an
      association that is partially mediated by body composition.

PMID- 19106274
TI  - The Finnish Diabetes Risk Score is associated with insulin resistance and
      progression towards type 2 diabetes.
AB  - OBJECTIVE: The Finnish Diabetes Risk Score (FINDRISC) questionnaire is a
      practical screening tool to estimate the diabetes risk and the probability of
      asymptomatic type 2 diabetes. In this study we evaluated the usefulness of the
      FINDRISC to predict insulin resistance in a population at increased diabetes
      risk. DESIGN: Data of 771 and 526 participants in a cross-sectional survey (1996)
      and a cohort study (1997-2000), respectively, were used for the analysis. Data on
      the FINDRISC and oral glucose tolerance test parameters were available from each
      participant. The predictive value of the FINDRISC was cross-sectionally evaluated
      using the area under the curve-receiver operating characteristics method and by
      correlation analyses. A validation of the cross-sectional results was performed
      on the prospective data from the cohort study. RESULTS: The FINDRISC was
      significantly correlated with markers of insulin resistance. The receiver
      operating characteristics-area under the curve for the prediction of a
      homeostasis model assessment insulin resistance index of more than five was 0.78
      in the cross-sectional survey and 0.74 at baseline of the cohort study. Moreover,
      the FINDRISC at baseline was significantly associated with disease evolution (P <
      0.01), which was defined as the change of glucose tolerance during the 3 yr
      follow-up. CONCLUSIONS: The results indicate that the FINDRISC can be applied to
      detect insulin resistance in a population at high risk for type 2 diabetes and
      predict future impairment of glucose tolerance.

PMID- 19106275
TI  - 100 years after Alzheimer: contemporary neurology practice assessment of
      referrals for dementia.
AB  - BACKGROUND: The prevalence of dementia is placing an increased burden on
      specialists. METHODS: Canadian neurologists responded to a structured
      questionnaire to assess reasons for referral and services provided as well as to
      compare the neurologists' perceptions of their practice characteristics against
      cases seen over a 3-month period. RESULTS: The audit confirmed the participants'
      perception that family practitioners are the main referral source (358/453, 79%).
      Sixty-two percent of patients had undergone clinical investigation for dementia
      prior to being seen by the neurologist; 39% (177/453) were on pharmacotherapy at
      the time of referral, 68% were initiated on pharmacotherapy by the neurologist. A
      fifth of the referrals did not meet clinical criteria for dementia, which may be
      directly related to the prevalence of prior workup that did not include mental
      status testing. CONCLUSIONS: Neurologists currently treat patients referred for
      dementia who may already have been adequately evaluated and treated by primary
      care providers.

PMID- 19106276
TI  - Persons with mild or moderate Alzheimer's disease managing daily activities via
      verbal instruction technology.
AB  - Four studies assessed the effectiveness of verbal instructions presented via
      technology in helping persons with mild or moderate Alzheimer's disease perform
      daily activities. The first 2 studies were replication efforts concerning morning
      bathroom routine and table setting and included 4 and 2 participants,
      respectively. The third study targeted coffee preparation with 3 participants.
      The fourth study assessed maintenance and generalization of morning bathroom
      routine and dressing with 1 participant. Nonconcurrent multiple baseline designs
      served for the first 3 studies and a 5-month postintervention data collection for
      the fourth study. Verbal instructions for the activity steps presented via
      technology were effective in helping the participants of the first 3 studies
      reacquire basic daily activities and the participant of the fourth study retain
      the reacquired activities across time and settings. These results suggest that
      the approach reported may be a useful strategy for helping persons with
      Alzheimer's disease.

PMID- 19106277
TI  - Monitoring "De Novo"APP synthesis by taking advantage of the reversible effect of
      cycloheximide.
AB  - By blocking "de novo" protein synthesis using cycloheximide, we previously
      described a dynamic model system to monitor turnover of a specific population of
      the Alzheimer's amyloid precursor protein. Here we show that cycloheximide is
      nontoxic and its effect is reversible, allowing protein synthesis to reinitiate.
      Upon cycloheximide removal protein synthesis restarted and by 1 hour the amyloid
      precursor protein- green fluorescent protein could be clearly detected,
      permitting the monitoring of amyloid precursor protein anterograde transport,
      particularly the secretory pathway. The consensus NPTY motif in amyloid precursor
      protein, typically associated with endocytosis, was mutated to NPTF or NPTE to
      mimic a constitutively dephosphorylated or phosphorylated residue, respectively.
      Our data reveal that disruption of this motif affects amyloid precursor protein
      endocytosis, as shown previously, but also its incorporation into trans-Golgi
      network budding vesicles. Thus, cycloheximide can be a useful tool to study both
      anterograde and retrograde "in vivo'' protein transport.

PMID- 19106278
TI  - Management of neuropathic cancer pain following WHO analgesic ladder: a
      prospective study.
AB  - Cancer pain treatment according to the guidelines of World Health Organization
      (WHO) is effective and safe in majority of patients. 818 neuropathic cancer pain
      patients were enrolled in the study and pain was managed according to WHO
      analgesic ladder and followed up to six months. Main adjuvant drugs used were
      amitryptaline (29.9%), gabapentin (29.9%) and gabapentine with dexamethasone in
      (19.9%) and dexamethasone alone in (20.2%) patients. Opioids prescribed were
      mainly tramadol, codeine sulphate and morphine. 52% patients received morphine as
      rescue analgesic. At the end of six months 53.2% patients had no pain and 41.9%
      of patients had mild pain as compared to 0% and 10.2% patients respectively at
      the first visit. 4.9% of patients had moderate pain even after the treatment.
      Neuropathic cancer pain can be relieved by multimodal treatment following WHO
      guidelines as majority of cancer patients suffered multiple types of pain.

PMID- 19106279
TI  - Ethical issues for hospice volunteers.
AB  - Health care professionals usually receive professional education in ethics, but
      the half million hospice volunteers in the United States may receive only brief
      training that is limited to confidentiality and the volunteer role. The purpose
      of this study was to explore ethical issues hospice volunteers confront in their
      work. Interviews with 39 hospice volunteers were conducted, audio recorded,
      transcribed, and analyzed using qualitative methods. Prominent themes were
      dilemmas about gifts, patient care and family concerns, issues related to
      volunteer roles and boundaries, and issues surrounding suicide and hastening
      death. Suggestions for training include discussions of ethics after initial
      training once volunteers had confronted ethical issues, with special emphasis on
      strategies for negotiating their uneasy role positioned between health care
      professional and friend.

PMID- 19106280
TI  - Use of complementary and alternative medicine (CAM) by Washington State hospices.
AB  - PURPOSE: To assess the use of complementary and alternative medicine in hospice
      care in the state of Washington. METHODS: Hospices offering inpatient and
      outpatient care in Washington State were surveyed by phone interview. RESULTS:
      Response rate was 100%. Results indicated that 86% of Washington State hospices
      offered complementary and alternative services to their patients, most frequently
      massage (87%), music therapy (74%), energy healing (65%), aromatherapy (45%),
      guided imagery (45%), compassionate touch (42%), acupuncture (32%), pet therapy
      (32%), meditation (29%), art therapy (22%), reflexology (19%), and hypnotherapy
      (16%). Most hospices relied on volunteers with or without small donations to
      offer such services. CONCLUSIONS: Complementary and alternative therapies are
      widely used by Washington State hospices but not covered under hospice benefits.
      Extensive use of these therapies seems to warrant the inclusion of complementary
      and alternative providers as part of hospice staff, and reimbursement schedules
      need to be integrated into hospice care.

PMID- 19106281
TI  - Palliative medicine Death Rounds: small group learning on a vital subject.
AB  - BACKGROUND: The medical student's experience with patients' dying and death has
      profound impact on personal and professional development. Death Rounds at the
      University of New Mexico School of Medicine is a small group educational model
      that promotes student self-reflection, metacognition, professional growth, and
      collegial support. OBJECTIVE: To describe the implementation and evaluation
      activities of a third year clerkship Death Rounds which are a structured,
      institutionally supported resource for helping students to understand the
      clinical, ethical, legal, professional, cultural, and spiritual aspects of death.
      DESIGN: Medical students attend 2 to 3 small group palliative medicine Death
      Rounds sessions, facilitated by the attending clerkship director, chief
      residents, and a palliative care physician. CONCLUSIONS: The students' assessment
      of their palliative medicine knowledge and skills in 5 categories before and
      after participation in Death Rounds rated their skills after Death Rounds higher
      with effect sizes ranging from 0.9 to 1.9. Evidence from both the Death Rounds
      Questionnaire and Facilitators' Logs demonstrates that multiple issues and topics
      were addressed and all associated with the School of Medicine's 6 core
      competencies. Death Rounds minimally affect on clerkship time and faculty
      resources.

PMID- 19106282
TI  - Peaceful surrender to death without futile bargaining to live relieves terminal
      air hunger and anguish.
AB  - The case report emphasizes the management of "terminal air hunger and anguish''
      as a major challenge for the palliative care physicians. Truthful and
      compassionate terminal counseling of the patient and terminal sedation allowed us
      to control this distressing final phase of dying in the metastatic lung disease
      and enabled the patient to take her last breath peacefully.

PMID- 19106284
TI  - Goals of care toward the end of life: a structured literature review.
AB  - Goals of care are often mentioned as an important component of end-of-life
      discussions, but there are diverse assessments regarding the type and number of
      goals that should be considered. To address this lack of consensus, we searched
      MEDLINE (1967-2007) for relevant articles and identified the number, phrasing,
      and type of goals they addressed. An iterative process of categorization resulted
      in a list of 6 practical, comprehensive goals: (1) be cured, (2) live longer, (3)
      improve or maintain function/quality of life/ independence, (4) be comfortable,
      (5) achieve life goals, and (6) provide support for family/caregiver. These goals
      can be used to articulate goal-oriented frameworks to guide decision making
      toward the end of life and thereby harmonize patients' treatment choices with
      their values and medical conditions.

PMID- 19106285
TI  - Seven hours in a ditch.

PMID- 19106286
TI  - The prevalence of low triiodothyronine according to the stage of chronic kidney
      disease in subjects with a normal thyroid-stimulating hormone.
AB  - BACKGROUND: We hypothesized that the prevalence of low T3 would be increased
      according to the increase in CKD stage. This study was performed to explore the
      prevalence in each stage of CKD and relationship with eGFR. METHODS: A total of
      2284 cases with normal thyroid-stimulating hormone (TSH) level were enrolled and
      retrospectively analysed during the recent period, from July 2005 to December
      2007. RESULTS: There was an increasing trend for the population of low T3
      according to the increase of a CKD stage (eGFR > or = 90, 8.2%; > or = 60 eGFR <
      90, 10.9%; > or = 30 eGFR < 60, 20.8%; > or = 15 eGFR < 30, 60.6%; eGFR < 15,
      78.6%). Also, there was positive relationship between eGFR and serum T3 in male,
      female and total subjects. After adjusting for age and sex, compared with eGFR >
      or = 60 ml/min/ 1.73 m2, eGFR < 60 ml/min/1.73 m2 was associated with an
      increased odds of low T3 [odds ratio 2.40 (CI: 1.5315 to 3.1731)]. In multiple
      regression analysis, eGFR was positively related with T3 (standardized
      coefficient 0.143, R2 = 0.055, P < 0.001), independent of age and serum albumin.
      CONCLUSION: This study showed that low T3 syndrome was highly prevalent in CKD
      and was a remarkable finding in early CKD. Furthermore, serum T3 levels were
      associated with severity of CKD even in the normal TSH level.

PMID- 19106287
TI  - Serum-based microRNAs: are we blinded by potential?

PMID- 19106288
TI  - Vitamin B deficiency causes neural cell loss and cognitive impairment in the
      developing rat.

PMID- 19106289
TI  - Coastal eutrophication: whether N and/or P should be abated depends on the
      dynamic mass balance.

PMID- 19106290
TI  - Simultaneous behavioral characterizations: Embracing complexity.

PMID- 19106291
TI  - Mice lacking asparaginyl endopeptidase develop disorders resembling
      hemophagocytic syndrome.
AB  - Asparaginyl endopeptidase (AEP or legumain) is a lysosomal cysteine protease that
      cleaves protein substrates on the C-terminal side of asparagine. AEP plays a
      pivotal role in the endosome/lysosomal degradation system and is implicated in
      antigen processing. The processing of the lysosomal proteases cathepsins in
      kidney is completely defective in AEP-deficient mice with accumulation of
      macromolecules in the lysosomes, which is typically seen in lysosomal disorders.
      Here we show that mutant mice lacking AEP develop fever, cytopenia,
      hepatosplenomegaly, and hemophagocytosis, which are primary pathological
      manifestations of hemophagocytic syndrome/hemophagocytic lymphohistiocytosis
      (HLH). Moreover, AEP deficiency provokes extramedullary hematopoiesis in the
      spleen and abnormally enlarged histiocytes with ingested red blood cells (RBCs)
      in bone marrow. Interestingly, RBCs from AEP-null mice are defective in plasma
      membrane components. Further, AEP-null mice display lower natural killer cell
      activity, but none of the major cytokines is substantially abnormal. These
      results indicate that AEP might be a previously unrecognized component in HLH
      pathophysiology.

PMID- 19106292
TI  - Use of the Rad51 promoter for targeted anti-cancer therapy.
AB  - Rad51 protein, involved in homologous recombination, is overexpressed in a
      variety of tumors, and its expression is correlated with a poor prognosis. Here
      we propose to exploit the overexpression of Rad51 in cancer cells to design a
      Rad51 promoter-based anticancer therapy. On average, Rad51 mRNA and protein
      levels are increased in cancer cells four- and sixfold, respectively.
      Serendipitously, we discovered that when the Rad51 ORF is replaced with another
      ORF, the difference in promoter activity between normal and cancer cells
      increases to an average of 840-fold with a maximum difference of 12,500-fold.
      This dramatic difference in activity has high therapeutic potential. We
      demonstrate that the fusion of Rad51 promoter to diphtheria toxin A (DTA) gene
      kills a variety of cancer cell types, including breast cancer, fibrosarcoma, and
      cervical cancer cells, with minimal effect on normal breast epithelial cells and
      normal fibroblasts. Our results suggest that therapies based on the Rad51
      promoter will be highly tumor specific and open new avenues for targeting a broad
      range of cancers.

PMID- 19106293
TI  - Ion-water hydrogen-bond switching observed with 2D IR vibrational echo chemical
      exchange spectroscopy.
AB  - The exchange of water hydroxyl hydrogen bonds between anions and water oxygens is
      observed directly with ultrafast 2D IR vibrational echo chemical exchange
      spectroscopy (CES). The OD hydroxyl stretch of dilute HOD in H(2)O in
      concentrated (5.5 M) aqueous solutions of sodium tetrafluoroborate (NaBF(4))
      displays a spectrum with a broad water-like band (hydroxyl bound to water oxygen)
      and a resolved, blue shifted band (hydroxyl bound to BF(4)(-)). At short time
      (200 fs), the 2D IR vibrational echo spectrum has 4 peaks, 2 on the diagonal and
      2 off-diagonal. The 2 diagonal peaks are the 0-1 transitions of the water-like
      band and the hydroxyl-anion band. Vibrational echo emissions at the 1-2
      transition frequencies give rise to 2 off-diagonal peaks. On a picosecond time
      scale, additional off-diagonal peaks grow in. These new peaks arise from chemical
      exchange between water hydroxyls bound to anions and hydroxyls bound to water
      oxygens. The growth of the chemical exchange peaks yields the time dependence of
      anion-water hydroxyl hydrogen bond switching under thermal equilibrium conditions
      as T(aw) = 7 +/- 1 ps. Pump-probe measurements of the orientational relaxation
      rates and vibrational lifetimes are used in the CES data analysis. The pump-probe
      measurements are shown to have the correct functional form for a system
      undergoing exchange.

PMID- 19106294
TI  - A consensus view of DNA binding by the C family of replicative DNA polymerases.

PMID- 19106295
TI  - A robust automated system elucidates mouse home cage behavioral structure.
AB  - Patterns of behavior exhibited by mice in their home cages reflect the function
      and interaction of numerous behavioral and physiological systems. Detailed
      assessment of these patterns thus has the potential to provide a powerful tool
      for understanding basic aspects of behavioral regulation and their perturbation
      by disease processes. However, the capacity to identify and examine these
      patterns in terms of their discrete levels of organization across diverse
      behaviors has been difficult to achieve and automate. Here, we describe an
      automated approach for the quantitative characterization of fundamental
      behavioral elements and their patterns in the freely behaving mouse. We
      demonstrate the utility of this approach by identifying unique features of home
      cage behavioral structure and changes in distinct levels of behavioral
      organization in mice with single gene mutations altering energy balance. The
      robust, automated, reproducible quantification of mouse home cage behavioral
      structure detailed here should have wide applicability for the study of mammalian
      physiology, behavior, and disease.

PMID- 19106296
TI  - Two-phase increase in the maximum size of life over 3.5 billion years reflects
      biological innovation and environmental opportunity.
AB  - The maximum size of organisms has increased enormously since the initial
      appearance of life >3.5 billion years ago (Gya), but the pattern and timing of
      this size increase is poorly known. Consequently, controls underlying the size
      spectrum of the global biota have been difficult to evaluate. Our period-level
      compilation of the largest known fossil organisms demonstrates that maximum size
      increased by 16 orders of magnitude since life first appeared in the fossil
      record. The great majority of the increase is accounted for by 2 discrete steps
      of approximately equal magnitude: the first in the middle of the Paleoproterozoic
      Era (approximately 1.9 Gya) and the second during the late Neoproterozoic and
      early Paleozoic eras (0.6-0.45 Gya). Each size step required a major innovation
      in organismal complexity--first the eukaryotic cell and later eukaryotic
      multicellularity. These size steps coincide with, or slightly postdate, increases
      in the concentration of atmospheric oxygen, suggesting latent evolutionary
      potential was realized soon after environmental limitations were removed.

PMID- 19106297
TI  - Population genetics of Trypanosoma brucei gambiense, the agent of sleeping
      sickness in Western Africa.
AB  - Human African trypanosomiasis, or sleeping sickness caused by Trypanosoma brucei
      gambiense, occurs in Western and Central Africa. T. brucei s.l. displays a huge
      diversity of adaptations and host specificities, and questions about its
      reproductive mode, dispersal abilities, and effective size remain under debate.
      We have investigated genetic variation at 8 microsatellite loci of T. b.
      gambiense strains isolated from human African trypanosomiasis patients in the
      Ivory Coast and Guinea, with the aim of knowing how genetic information was
      partitioned within and between individuals in both temporal and spatial scales.
      The results indicate that (i) migration of T. b. gambiense group 1 strains does
      not occur at the scale of West Africa, and that even at a finer scale (e.g.,
      within Guinea) migration is restricted; (ii) effective population sizes of
      trypanosomes, as reflected by infected hosts, are probably higher than what the
      epidemiological surveys suggest; and (iii) T. b. gambiense group 1 is most likely
      a strictly clonally reproducing organism.

PMID- 19106298
TI  - Structure of PolC reveals unique DNA binding and fidelity determinants.
AB  - PolC is the polymerase responsible for genome duplication in many Gram-positive
      bacteria and represents an attractive target for antibacterial development. We
      have determined the 2.4-A resolution crystal structure of Geobacillus
      kaustophilus PolC in a ternary complex with DNA and dGTP. The structure reveals
      nascent base pair interactions that lead to highly accurate nucleotide
      incorporation. A unique beta-strand motif in the PolC thumb domain contacts the
      minor groove, allowing replication errors to be sensed up to 8 nt upstream of the
      active site. PolC exhibits the potential for large-scale conformational
      flexibility, which could encompass the catalytic residues. The structure suggests
      a mechanism by which the active site can communicate with the rest of the
      replisome to trigger proofreading after nucleotide misincorporation, leading to
      an integrated model for controlling the dynamic switch between replicative and
      repair polymerases. This ternary complex of a cellular replicative polymerase
      affords insights into polymerase fidelity, evolution, and structural diversity.

PMID- 19106299
TI  - Incremental steps toward incompatibility revealed by Arabidopsis epistatic
      interactions modulating salicylic acid pathway activation.
AB  - Plant growth is influenced by genetic factors and environmental cues. Genotype-by
      environment interactions are governed by complex genetic epistatic networks that
      are subject to natural selection. Here we describe a novel epistatic interaction
      modulating growth in response to temperature common to 2 Arabidopsis recombinant
      inbred line (RIL) populations (Ler x Kas-2 and Ler x Kond). At 14 degrees C,
      lines with specific allele combinations at interacting loci (incompatible
      interactions) have severe growth defects. These lines exhibit deregulated cell
      death programs and enhanced disease resistance. At 20 degrees C, growth defects
      are suppressed, but a positive trait of enhanced resistance is retained. Mapping
      of 1 interacting QTL to a cluster of RPP1-like TIR-NB-LRR genes on chromosome 3
      is consistent with our finding that environmentally conditioned epistasis depends
      on activation of the salicylic acid (SA) stress signaling pathway. The nature of
      the epistatic interaction conforms to the Dobzhansky-Muller model of genetic
      incompatibility with incomplete penetrance for reproductive isolation. Variation
      in fitness of different incompatible lines reveals the presence of additional
      modifiers in the genetic background. We propose that certain interacting loci
      lead to an optimal balance between growth and resistance to pathogens by
      modulating SA signaling under specific environments. This could allow the
      accumulation of additional incompatibilities before reaching complete
      reproductive isolation.

PMID- 19106300
TI  - Association of the circadian rhythmic expression of GmCRY1a with a latitudinal
      cline in photoperiodic flowering of soybean.
AB  - Photoperiodic control of flowering time is believed to affect latitudinal
      distribution of plants. The blue light receptor CRY2 regulates photoperiodic
      flowering in the experimental model plant Arabidopsis thaliana. However, it is
      unclear whether genetic variations affecting cryptochrome activity or expression
      is broadly associated with latitudinal distribution of plants. We report here an
      investigation of the function and expression of two cryptochromes in soybean,
      GmCRY1a and GmCRY2a. Soybean is a short-day (SD) crop commonly cultivated
      according to the photoperiodic sensitivity of cultivars. Both cultivated soybean
      (Glycine max) and its wild relative (G. soja) exhibit a strong latitudinal cline
      in photoperiodic flowering. Similar to their Arabidopsis counterparts, both
      GmCRY1a and GmCRY2a affected blue light inhibition of cell elongation, but only
      GmCRY2a underwent blue light- and 26S proteasome-dependent degradation. However,
      in contrast to Arabidopsis cryptochromes, soybean GmCRY1a, but not GmCRY2a,
      exhibited a strong activity promoting floral initiation, and the level of protein
      expression of GmCRY1a, but not GmCRY2a, oscillated with a circadian rhythm that
      has different phase characteristics in different photoperiods. Consistent with
      the hypothesis that GmCRY1a is a major regulator of photoperiodic flowering in
      soybean, the photoperiod-dependent circadian rhythmic expression of the GmCRY1a
      protein correlates with photoperiodic flowering and latitudinal distribution of
      soybean cultivars. We propose that genes affecting protein expression of the
      GmCRY1a protein play an important role in determining latitudinal distribution of
      soybeans.

PMID- 19106301
TI  - Replacement of normal with mutant alleles in the genome of normal human cells
      unveils mutation-specific drug responses.
AB  - Mutations in oncogenes and tumor suppressor genes are responsible for
      tumorigenesis and represent favored therapeutic targets in oncology. We exploited
      homologous recombination to knock-in individual cancer mutations in the genome of
      nontransformed human cells. Sequential introduction of multiple mutations was
      also achieved, demonstrating the potential of this strategy to construct tumor
      progression models. Knock-in cells displayed allele-specific activation of
      signaling pathways and mutation-specific phenotypes different from those
      obtainable by ectopic oncogene expression. Profiling of a library of
      pharmacological agents on the mutated cells showed striking sensitivity or
      resistance phenotypes to pathway-targeted drugs, often matching those of tumor
      cells carrying equivalent cancer mutations. Thus, knock-in of single or multiple
      cancer alleles provides a pharmacogenomic platform for the rational design of
      targeted therapies.

PMID- 19106302
TI  - Distinct roles of GSK-3alpha and GSK-3beta phosphorylation in the heart under
      pressure overload.
AB  - Glycogen synthase kinase-3 (GSK-3) is a master regulator of growth and death in
      cardiac myocytes. GSK-3 is inactivated by hypertrophic stimuli through
      phosphorylation-dependent and -independent mechanisms. Inactivation of GSK-3
      removes the negative constraint of GSK-3 on hypertrophy, thereby stimulating
      cardiac hypertrophy. N-terminal phosphorylation of the GSK-3 isoforms GSK-3alpha
      and GSK-3beta by upstream kinases (e.g., Akt) is a major mechanism of GSK-3
      inhibition. Nonetheless, its role in mediating cardiac hypertrophy and failure
      remains to be established. Here we evaluated the role of Serine(S)21 and S9
      phosphorylation of GSK-3alpha and GSK-3beta in the regulation of cardiac
      hypertrophy and function during pressure overload (PO), using GSK-3alpha S21A
      knock-in (alphaKI) and GSK-3beta S9A knock-in (betaKI) mice. Although inhibition
      of S9 phosphorylation during PO in the betaKI mice attenuated hypertrophy and
      heart failure (HF), inhibition of S21 phosphorylation in the alphaKI mice
      unexpectedly promoted hypertrophy and HF. Inhibition of S21 phosphorylation in
      GSK-3alpha, but not of S9 phosphorylation in GSK-3beta, caused phosphorylation
      and down-regulation of G1-cyclins, due to preferential localization of GSK-3alpha
      in the nucleus, and suppressed E2F and markers of cell proliferation, including
      phosphorylated histone H3, under PO, thereby contributing to decreases in the
      total number of myocytes in the heart. Restoration of the E2F activity by
      injection of adenovirus harboring cyclin D1 with a nuclear localization signal
      attenuated HF under PO in the alphaKI mice. Collectively, our results reveal that
      whereas S9 phosphorylation of GSK-3beta mediates pathological hypertrophy, S21
      phosphorylation of GSK-3alpha plays a compensatory role during PO, in part by
      alleviating the negative constraint on the cell cycle machinery in cardiac
      myocytes.

PMID- 19106303
TI  - Mechanism of a prototypical synthetic membrane-active antimicrobial: Efficient
      hole-punching via interaction with negative intrinsic curvature lipids.
AB  - Phenylene ethynylenes comprise a prototypical class of synthetic antimicrobial
      compounds that mimic antimicrobial peptides produced by eukaryotes and have broad
      spectrum antimicrobial activity. We show unambiguously that bacterial membrane
      permeation by these antimicrobials depends on the presence of negative intrinsic
      curvature lipids, such as phosphatidylethanolamine (PE) lipids, found in high
      concentrations within bacterial membranes. Plate-killing assays indicate that a
      PE-knockout mutant strain of Escherichia coli drastically out-survives the wild
      type against the membrane-active phenylene ethynylene antimicrobials, whereas the
      opposite is true when challenged with traditional metabolic antibiotics. That the
      PE deletion is a lethal mutation in normative environments suggests that
      resistant bacterial strains do not evolve because a lethal mutation is required
      to gain immunity. PE lipids allow efficient generation of negative curvature
      required for the circumferential barrel of an induced membrane pore; an inverted
      hexagonal H(II) phase, which consists of arrays of water channels, is induced by
      a small number of antimicrobial molecules. The estimated antimicrobial occupation
      in these water channels is nonlinear and jumps from approximately 1 to 3 per 4 nm
      of induced water channel length as the global antimicrobial concentration is
      increased. By comparing to exactly solvable 1D spin models for magnetic systems,
      we quantify the cooperativity of these antimicrobials.

PMID- 19106305
TI  - Retraction for Prasad et al., Characterization of capsaicin synthase and
      identification of its gene (csy1) for pungency factor capsaicin in pepper
      (Capsicum sp.).

PMID- 19106304
TI  - Glyconanoparticles allow pre-symptomatic in vivo imaging of brain disease.
AB  - Initial recruitment of leukocytes in inflammation associated with diseases such
      as multiple sclerosis (MS), ischemic stroke, and HIV-related dementia, takes
      place across intact, but activated brain endothelium. It is therefore
      undetectable to symptom-based diagnoses and cannot be observed by conventional
      imaging techniques, which rely on increased permeability of the blood-brain
      barrier (BBB) in later stages of disease. Specific visualization of the early
      activated cerebral endothelium would provide a powerful tool for the
      presymptomatic diagnosis of brain disease and evaluation of new therapies. Here,
      we present the design, construction and in vivo application of carbohydrate
      functionalized nanoparticles that allow direct detection of endothelial markers E
      /P-selectin (CD62E/CD62P) in acute inflammation. These first examples of MRI
      visible glyconanoparticles display multiple copies of the natural complex glycan
      ligand of selectins. Their resulting sensitivity and binding selectivity has
      allowed acute detection of disease in mammals with beneficial implications for
      treatment of an expanding patient population suffering from neurological disease.

PMID- 19106306
TI  - Genetic variation in the promoter region of chitinase 3-like 1 is associated with
      atopy.
AB  - RATIONALE: Atopy or atopic syndrome is an allergic hypersensitivity subject to
      hereditary influences. Aberrant expression of chitinase 3-like 1 (CHI3L1), also
      known as YKL-40 or HC gp-39, is involved in the pathogenesis of inflammatory and
      allergic diseases. OBJECTIVES: The genetic contribution of CHI3L1 gene to atopic
      susceptibility was investigated using an integrated population genetic and
      molecular analysis. METHODS: Genetic variations in CHI3L1 were identified and
      genotyped in 295 unrelated patients with atopy and 180 control subjects. Serum
      YKL-40 and IgE levels were analyzed according to genotype. The effects of a
      promoter polymorphism (g.-247C/T) on promoter activity were examined in reporter
      and protein binding assays. MEASUREMENTS AND MAIN RESULTS: In the case-control
      association analysis, the g.-247C/T polymorphism at the promoter region
      (rs10399805; P = 0.0062) and the IVS7+82C/T polymorphism at intron 7 (rs2275353;
      P = 0.0056) of CHI3L1 showed a significant association with atopy. Subjects with
      the g.-247T risk allele had significantly higher serum YKL-40 (P < 0.0001) and
      IgE (P = 0.012) levels. An in vitro promoter assay using THP-1 human monocyte
      cells revealed that the C to T conversion at g.-247 induced a more than twofold
      increase of reporter gene expression. Moreover, the g.-247T allele showed an
      increased affinity for CCAAT enhancer-binding protein, a well known
      transcriptional activator, by electrophoretic mobility shift assay. Accordingly,
      subjects with the g.-247TT genotype showed a 2.5-fold increase in CHI3L1 mRNA
      expression in peripheral blood cells compared with those with the g.-247CC
      genotype. CONCLUSIONS: These results strongly suggest that the g.-247C/T
      polymorphism in the CHI3L1 promoter region is associated with the risk of atopy.

PMID- 19106308
TI  - Perinatal alcohol exposure in rat induces long-term depression of respiration
      after episodic hypoxia.
AB  - RATIONALE: Little is known about the effects of alcohol exposure during
      pregnancy, which is responsible for fetal alcohol syndrome and the respiratory
      network functions, especially respiratory network plasticity (e.g., long-term
      facilitation) elicited after repeated short-lasting hypoxic episodes. The
      mechanism of induction of respiratory long-term facilitation involves 5-HT(2A/2C)
      receptors, which also participate in the response to hypoxia. Because fetal
      alcohol exposure is known to reduce serotonin centrally, and synaptic plasticity
      in the hippocampus, we hypothesized that alcohol exposure during gestation might
      impair respiratory long-term facilitation after hypoxic episodes. OBJECTIVES: To
      analyze the effects of prenatal and postnatal alcohol exposure on respiratory
      long-term facilitation in 5- to 7-day-old rats. METHODS: Respiratory frequency
      and amplitude were measured in vivo and in an in vitro rhythmic medullary slice
      before and after three hypoxia episodes or three applications of a 5-HT(2A/2C)
      receptor agonist in vitro. 5-HT(2A/2C) receptor mRNA was measured from the slice.
      MEASUREMENTS AND MAIN RESULTS: Alcohol exposure impaired respiratory long-term
      facilitation and induced long-term depression of respiration in both in vivo and
      in vitro models. Alcohol altered 5-HT(2A/2C) mRNA expression, although 5
      HT(2A/2C) agonist efficacy was not altered in increasing rhythmic activity in
      slices. However, a higher concentration of 5-HT(2A/2C) agonist was necessary to
      induce transient facilitation in slices from ethanol-exposed animals, suggesting
      disturbances in induction and maintenance mechanisms of respiratory long-term
      facilitation. CONCLUSIONS: Respiratory facilitation after repeated hypoxia was
      converted to long-term depression in rats treated with alcohol in utero. Alcohol
      exposure during pregnancy may therefore induce long-term maladaptive behavior of
      the respiratory system in neonates.

PMID- 19106307
TI  - Down-regulation of the notch pathway in human airway epithelium in association
      with smoking and chronic obstructive pulmonary disease.
AB  - RATIONALE: The airway epithelium of smokers is subject to a variety of mechanisms
      of injury with consequent modulation of epithelial regeneration and disordered
      differentiation. Several signaling pathways, including the Notch pathway, control
      epithelial differentiation in lung morphogenesis, but little is known about the
      role of these pathways in adults. OBJECTIVES: We tested the hypotheses that Notch
      related genes are expressed in the normal nonsmoker small airway epithelium of
      human adults, and that Notch-related gene expression is down-regulated in healthy
      smokers and smokers with chronic obstructive pulmonary disease (COPD). METHODS:
      We used microarray technology to evaluate the expression of 55 Notch-related
      genes in the small airway epithelium of nonsmokers. We used TaqMan quantitative
      polymerase chain reaction (PCR) to confirm the expression of key genes and we
      used immunohistochemistry to assess the expression of Notch-related proteins in
      the airway epithelium. Changes in expression of Notch genes in healthy smokers
      and smokers with COPD compared with nonsmokers were evaluated by PCR.
      MEASUREMENTS AND MAIN RESULTS: Microarray analysis demonstrated that 45 of 55
      Notch-related genes are expressed in the small airway epithelium of adults.
      TaqMan PCR confirmed the expression of key genes with highest expression of the
      ligand DLL1, the receptor NOTCH2, and the downstream effector HES1.
      Immunohistochemistry demonstrated the expression of Jag1, Notch2, Hes1, and Hes5
      in airway epithelium. Several Notch ligands, receptors, and downstream effector
      genes were down-regulated in smokers, with more genes down-regulated in smokers
      with COPD than in healthy smokers. CONCLUSIONS: These observations are consistent
      with the hypothesis that the Notch pathway likely plays a role in the human adult
      airway epithelium, with down-regulation of Notch pathway gene expression in
      association with smoking and COPD.

PMID- 19106309
TI  - Methods appropriate for studying the relationship of breast-feeding to obesity.
AB  - A vast literature examines the association of breast-feeding with body
      composition and risk of overweight and obesity in childhood and adulthood.
      Several recent systematic reviews, including one by the World Health
      Organization, concluded that there is a small protective effect of breast-feeding
      against overweight in later life. Nearly all studies covered by these reviews
      used observational study designs that limit causal inferences. Methodological
      strengths, weaknesses, and main results of the epidemiologic studies that have
      drawn conclusions about the relation between infant feeding and overweight in
      childhood and adulthood are briefly reviewed to provide a methodological
      perspective for the subsequent presentations in this symposium. The focus is on
      the role of recall and selection bias, appropriate representation of exposures,
      inadequate control for confounding, and the utility of alternative study designs
      that may circumvent some of the problems.

PMID- 19106311
TI  - Orally administered ovine serum immunoglobulins influence growth performance,
      organ weights, and gut morphology in growing rats.
AB  - In this study, our aim was to determine whether orally administered ovine serum
      Ig improved growth performance, organ weights, and gut morphology in growing rats
      and whether the method of manufacture of ovine serum Ig affected its bioactivity.
      Ninety Sprague-Dawley male rats were used in a 21-d growth study and were fed a
      basal control diet (BD; no Ig) and 5 test diets: spray-dried porcine plasma
      (SDPP), freeze-dried ovine Ig (FDOI), 2 concentrations of spray-dried ovine Ig
      (SDOI(100) and SDOI(150)), and inactivated ovine Ig (IOI). Diets were isocaloric
      and contained the same amount of the first limiting amino acids, methionine plus
      cysteine. The body weight gain:feed ratio was higher (P < 0.05) for the FDOI-fed
      rats than for the BD- and IOI-fed groups. FDOI rats had higher jejunum (P < 0.05)
      and colon weights (P < 0.05) at the end of the study than rats in the BD group.
      Compared with the SDOI(100)-fed group, the FDOI group supported higher (P < 0.05)
      duodenum and colon weights. For gut morphology, the FDOI and the BD and IOI
      groups differed (P < 0.05). The FDOI-fed rats had longer (P < 0.05) villi and
      greater villi surface areas in the duodenum, jejunum, and ileum than the rats fed
      SDOI(100). An ovine Ig fraction selectively improved growth performance, organ
      weight, and gut morphology in growing rats. Compared with spray-drying, a freeze
      drying procedure appears to preserve a higher degree of immunological activity.

PMID- 19106310
TI  - Dietary L-arginine supplementation reduces white fat gain and enhances skeletal
      muscle and brown fat masses in diet-induced obese rats.
AB  - Previous studies showed that dietary L-arginine supplementation decreased white
      fat mass in genetically obese rats. This study tested the effectiveness of L
      arginine in diet-induced obesity. Male Sprague-Dawley rats were fed for 15 wk a
      high-fat (HF) (40% energy) or low-fat (LF) (10% energy) diet beginning at 4 wk of
      age, resulting in 18% higher body weight gains and 74% higher weights of major
      white fat pads (retroperitoneal, epididymal, subcutaneous, and mesenteric adipose
      tissues) in HF than in LF fed rats. Starting at 19 wk of age, rats in each
      dietary group were supplemented for 12 wk with 1.51% L-arginine-HCl or 2.55% L
      alanine (isonitrogenous control) (n = 8 per treatment) in drinking water and
      arginine groups were individually pair-fed to alanine controls. Despite similar
      energy intake, absolute weights of white fat pads increased by 98% in control
      rats over a 12-wk period but only by 35% in arginine-supplemented rats. The
      arginine treatment reduced the relative weights of white fat pads by 30% and
      enhanced those of soleus muscle by 13%, extensor digitorum longus muscle by 11%,
      and brown fat by 34% compared with control rats. Serum concentrations of insulin,
      adiponectin, growth hormone, corticosterone, triiodothyronine, and thyroxine did
      not differ between control and arginine-supplemented rats. However, arginine
      treatment resulted in lower serum concentrations of leptin, glucose,
      triglycerides, urea, glutamine, and branched-chain amino acids, higher serum
      concentrations of nitric-oxide metabolites, and improvement in glucose tolerance.
      Thus, dietary arginine supplementation shifts nutrient partitioning to promote
      muscle over fat gain and may provide a useful treatment for improving the
      metabolic profile and reducing body white fat in diet-induced obese rats.

PMID- 19106312
TI  - Hidden fat facilitates passive overconsumption.
AB  - Food intake regulation may be disturbed when sensory signals from foods are
      disconnected from their metabolic properties. Consumption of high-fat, energy
      dense foods may stimulate passive overconsumption, because these foods do not
      provide sensory signals in accordance with the actual nutrient content. We
      examined the effects of perception of fat on energy intake in adults after
      overfeeding (Study 1) and on energy intake during a meal (Study 2). In study 1,
      57 participants consumed 6 mandatory lunches differing in energy level (100, 200,
      and 300% of a standard lunch intake) and fat condition (visible fat and hidden
      fat). Ad libitum energy intake was measured during subsequent meals. In Study 2,
      51 participants consumed 2 lunches that were high in visible or hidden fats. We
      measured ad libitum energy intake during lunch. In Study 1, the energy intake at
      dinner was 8% higher in the hidden fat condition than in the visible fat
      condition (P = 0.0046). A main effect was also found for the energy level of the
      lunch (P < 0.0001), with the highest intake following the 100% energy level and
      the lowest intake following the 300% energy level. In Study 2, the energy intake
      was 9% higher in the hidden fat condition than in the visible fat condition (P =
      0.013). Perception of fat influences energy intake. In the presence of visible
      fats, energy intake was lower than in the presence of hidden fats, suggesting
      that hidden fats may contribute to overconsumption. Appropriate sensory signals
      may be important in preventing overconsumption.

PMID- 19106313
TI  - A bovine whey protein extract can enhance innate immunity by priming normal human
      blood neutrophils.
AB  - Bovine milk-derived products, in particular whey proteins, exhibit beneficial
      properties for human health, including the acquired immune response. However,
      their effects on innate immunity have received little attention. Neutrophils are
      key cells of innate defenses through their primary functions of chemotaxis,
      phagocytosis, oxidative burst, and degranulation. A whey protein extract (WPE)
      purified from bovine lactoserum was evaluated for its direct and indirect effects
      on these primary functions of normal human blood neutrophils in vitro. Although
      WPE had no direct effects on primary functions, a 24-h pretreatment of
      neutrophils with WPE was associated with a significant and dose-dependent
      increase of their chemotaxis, superoxide production, and degranulation in
      response to N-formyl-methionine-leucine-phenylalanine, as well as of their
      phagocytosis of bioparticles. The pretreatment increased the surface expression
      of CD11b, CD16B, and CD32A receptors. The major WPE protein components beta
      lactoglobulin (beta-LG) and alpha-lactalbumin (alpha-LA) were the main active
      fractions having an additive effect on human neutrophils that became more
      responsive to a subsequent stimulation. This effect on NADPH oxidase activity was
      associated with translocation of p47(phox) to plasma membrane. Glycomacropeptide,
      a peptide present in measurable amounts in WPE products, was able to enhance the
      individual effect of beta-LG or alpha-LA on neutrophils. The present data suggest
      that WPE, through beta-LG and alpha-LA, has the capacity to enhance or "prime"
      human neutrophil responses to a subsequent stimulation, an effect that could be
      associated with increased innate defenses in vivo.

PMID- 19106314
TI  - Ferulaldehyde, a water-soluble degradation product of polyphenols, inhibits the
      lipopolysaccharide-induced inflammatory response in mice.
AB  - Antiinflammatory properties of polyphenols in natural products, traditional
      medicines, and healthy foods were recently attributed to highly soluble
      metabolites produced by the microflora of the intestines rather than the
      polyphenols themselves. To provide experimental basis for this hypothesis, we
      measured antiinflammatory properties of ferulaldehyde (FA), a natural
      intermediate of polyphenol metabolism of intestinal microflora, in a murine
      lipopolysaccharide (LPS)-induced septic shock model. We found that
      intraperitoneally administered FA (6 mg/kg) prolonged the lifespan of LPS-treated
      (40 mg/kg) mice, decreased the inflammatory response detected by T(2)-weighted in
      vivo MRI, decreased early proinflammatory cytokines such as tumor necrosis factor
      alpha and interleukin (IL)-1beta, and increased the antiinflammatory IL-10 in the
      sera of the mice. Additionally, FA inhibited LPS-induced activation of nuclear
      factor kappaB transcription factor in the liver of the mice. According to our
      data, these effects were probably due to attenuating LPS-induced activation of c
      Jun N-terminal kinase and Akt. Furthermore, FA decreased free radical and nitrite
      production in LPS plus interferon-gamma-treated primary mouse hepatocytes, whose
      effects are expected to contribute to its antiinflammatory property. These data
      provide direct in vivo evidence, that a water-soluble degradation product of
      polyphenols could be responsible for, or at least could significantly contribute
      to, the beneficial antiinflammatory effects of polyphenol-containing healthy
      foods, natural products, and traditional medicines.

PMID- 19106315
TI  - Lean body mass, not estrogen or progesterone, predicts peak bone mineral density
      in premenopausal women.
AB  - Estrogen and body fat content are important predictors of bone mineral density
      (BMD) in postmenopausal women, but their association with BMD in premenopausal
      women is less clear. Mounting evidence suggests that dietary fats can have
      detrimental effects on bone health. In a cross-sectional sample of healthy 30- to
      40-y-old women (n = 242), we investigated the predictors of BMD at the hip and
      spine by multilevel multiple regression analyses. Predictor variables in the
      models included dietary intake of various fats, serum concentrations of sex
      steroids, blood chemistries and markers of metabolic syndrome, anthropometric
      variables, and ethnicity. Among these premenopausal women, lean body mass was the
      strongest independent predictor (P < 0.0001) and African-American ethnicity (P <
      0.05) was another positive independent predictor of BMD at the hip and spine.
      Dietary fats were not independent predictors of BMD of hip and spine. Lean body
      mass and being African-American explained 33% of the variance in hip BMD. Lean
      body mass, African-American ethnicity, and serum concentrations of triglycerides
      (a negative predictor, P = 0.0001) explained 28% of the variance in spine BMD. In
      contrast, luteal phase serum concentrations of estradiol, progesterone, and
      testosterone were not predictors of BMD. It remains to be determined whether
      efforts to increase lean body mass in premenopausal women with normal levels of
      endogenous estrogen may be an effective preventive strategy to preserve bone
      health.

PMID- 19106316
TI  - Effects of dietary palmitoleic acid on plasma lipoprotein profile and aortic
      cholesterol accumulation are similar to those of other unsaturated fatty acids in
      the F1B golden Syrian hamster.
AB  - The lower susceptibility of palmitoleic acid (16:1) to oxidation compared to PUFA
      may confer functional advantages with respect to finding acceptable alternatives
      to partially hydrogenated fats, but limited data are available on its effect on
      cardiovascular risk factors. This study investigated the effect of diets (10%
      fat, 0.1% cholesterol, wt:wt) enriched with macadamia [monounsaturated fatty acid
      (MUFA)16:1], palm (SFA,16:0), canola (MUFA,18:1), or safflower (PUFA,18:2) oils
      on lipoprotein profiles and aortic cholesterol accumulation in F1B Golden Syrian
      hamsters (n = 16/group). After 12 wk, 8 hamsters in each group were killed (phase
      1). The remaining hamsters fed palm oil were changed to a diet containing coconut
      oil, while hamsters in the other diet groups continued on their original diets
      for an additional 6 wk (phase 2). With minor exceptions, the time course and
      dietary SFA source did not alter the study outcomes. Macadamia oil-fed hamsters
      had lower non-HDL cholesterol and triglyceride concentrations compared with the
      palm and coconut oil-fed hamsters and higher HDL-cholesterol compared with the
      coconut, canola, and safflower oil-fed hamsters. The aortic cholesterol
      concentration was not affected by dietary fat type. The hepatic cholesterol
      concentration was higher in the unsaturated compared with the saturated oil-fed
      hamsters. RBC membrane and aortic cholesteryl ester, triglyceride, and
      phospholipid fatty acid profiles reflected that of the dietary oil. These data
      suggest that an oil relatively high in palmitoleic acid does not adversely affect
      plasma lipoprotein profiles or aortic cholesterol accumulation and was similar to
      other unsaturated fatty acid-rich oils.

PMID- 19106317
TI  - Lipid metabolism predicts changes in body composition during energy restriction
      in overweight humans.
AB  - Dietary weight loss regimens could be more effective by selectively targeting
      adipose while sparing lean mass (LM) if predictive information about individuals'
      lipid metabolic responses to an intervention were available. The objective of
      this study was to examine the relationships among changes in 4 anthropometric
      outcomes, weight, waist circumference (WC), percent body fat (BF), and percent
      LM, and comprehensive circulating lipid metabolites in response to energy
      reduction in overweight participants. This was a cohort study (n = 46) from a
      larger multi-center (n = 105) weight loss trial. We used stepwise regression to
      examine relationships among baseline plasma fatty acids of 7 lipid classes,
      biochemical metabolites, and diet to explain the variance of 4 anthropometric
      outcomes after intervention. No predictor variables explained the variance in the
      percent change in body weight. The circulating concentration of FFA 18:1(n-9) at
      baseline explained 31% of the variance in percent change of WC, with adjustment
      for energy intake at 12 wk. Circulating concentrations of phosphatidylcholine
      18:0 and FFA 18:1(n-9) at baseline together explained 33% of the variance in
      percent LM change. The circulating concentration of phosphatidylcholine 18:0 at
      baseline explained 23% of the variance in the change in percent BF. This study
      determined relationships among comprehensive and quantitative measurements of
      complex lipid metabolites and metabolic outcomes as changes in body composition.
      Measurements of plasma circulating metabolites explained 20-30% of the variance
      in changes in body composition after a weight loss intervention. Thus,
      circulating lipids reflect lipid metabolism in relation to changes in body
      composition.

PMID- 19106318
TI  - Duration of breast-feeding and adiposity in adult life.
AB  - Few studies have examined whether the duration of breast-feeding is associated
      with BMI in adult life. In the past, the heights and weights of infants and the
      duration of breast-feeding were routinely recorded at infant welfare clinics in
      Helsinki, Finland. Most infants in the city were taken to these free clinics. The
      Helsinki Birth Cohort comprises 13,345 people born in the city during 1934-1944;
      84% were breast-fed. In 2001, a questionnaire was sent to members of the cohort
      asking about their weight and height. A random sample of 2003 men and women
      attended a clinic at which height, weight, and body composition were measured. We
      studied sibships that included 2 or more people from the cohort. There were 1823
      subjects: 831 had completed the questionnaire; 129 had attended the clinic. We
      grouped the subjects according to duration of breast-feeding: 0-2 mo, 3-4 mo, 5-7
      mo, and 8 mo or more. We compared siblings who were discordant for duration of
      breast-feeding. We found that a longer period of breast-feeding was associated
      with lower BMI at 1 y of age (P = 0.04 for a linear trend). This relation
      disappeared by the age of 7 y. People breast-fed for 5-7 mo had the lowest
      reported BMI at age 60 y, although this was not statistically significant; 8.8%
      more people breast-fed for 8 mo or more had reported BMIs that were overweight
      (25 to 30 kg/m(2)) compared with those breast-fed for shorter periods (P = 0.06).
      Breast-feeding for <2 mo or 8 mo or more was associated with an increased BMI and
      percentage body fat in later life, measured at the clinic (P = 0.08 and P = 0.03
      for quadratic trends). We conclude that breast-feeding for <2 mo may be
      deleterious, possibly because of lack of exposure to protective factors in breast
      milk. Breast-feeding beyond 8 mo may be deleterious because mother's hormones in
      breast milk reset the infant's hypothalamic-pituitary-thyroid axis.

PMID- 19106319
TI  - Biofortified black beans in a maize and bean diet provide more bioavailable iron
      to piglets than standard black beans.
AB  - Our objective was to compare the capacities of biofortified and standard black
      beans (Phaseolus vulgaris L.) to deliver iron (Fe) for hemoglobin (Hb) synthesis.
      Two lines of black beans, one standard and the other biofortified (high) in Fe
      (71 and 106 microg Fe/g, respectively), were used. Maize-based diets containing
      the beans were formulated to meet the nutrient requirements for swine except for
      Fe (Fe concentrations in the 2 diets were 42.9 +/- 1.2 and 54.6 +/- 0.9 mg/kg).
      At birth, pigs were injected with 50 mg of Fe as Fe dextran. At age 28 d, pigs
      were allocated to the experimental diets (n = 10). They were fed 2 times per day
      for 5 wk and given free access to water at all times. Body weights and Hb
      concentrations were measured weekly. Hb repletion efficiencies (means +/- SEM)
      did not differ between groups and, after 5 wk, were 20.8 +/- 2.1% for the
      standard Fe group and 20.9 +/- 2.1% for the high Fe group. Final total body Hb Fe
      contents did not differ between the standard [539 +/- 39 mg (9.7 +/- 0.7
      micromol)] and high Fe [592 +/- 28 mg (10.6 +/- 0.5 micromol)] bean groups (P =
      0.15). The increase in total body Hb Fe over the 5-wk feeding period was greater
      in the high Fe bean group [429 +/- 24 mg (7.7 +/- 0.4 micromol)] than in the
      standard Fe bean group [361 +/- 23 mg (6.4 +/- 0.4 micromol)] (P = 0.034). We
      conclude that the biofortified beans are a promising vehicle for increasing
      intakes of bioavailable Fe in human populations that consume beans as a dietary
      staple.

PMID- 19106320
TI  - Overweight is more prevalent than stunting and is associated with socioeconomic
      status, maternal obesity, and a snacking dietary pattern in school children from
      Bogota, Colombia.
AB  - The objectives of this study were to estimate the prevalence of overweight in
      school-aged children from Bogota, Colombia and to examine its associations with
      sociodemographic characteristics, dietary patterns, and indicators of physical
      activity. We measured height and weight in 3075 children between 5 and 12 y of
      age who attended public primary schools in 2006 and we obtained information on
      maternal sociodemographic and anthropometric characteristics. The survey was
      representative of children from low and middle socioeconomic backgrounds. The
      prevalences of child overweight (including obesity) and obesity according to the
      International Obesity Task Force criteria were 11.1 and 1.8%, respectively. The
      prevalence of stunting was 9.8%. In multivariate analysis, child overweight was
      positively associated with indicators of higher socioeconomic status (SES),
      including low maternal parity and ownership of household assets. The prevalence
      of overweight was 3.6 times greater in children whose mothers were obese compared
      with children whose mothers had an adequate BMI (adjusted prevalence ratio =
      3.61; 95% CI = 2.64, 4.93). Child overweight was positively associated with
      adherence to a "snacking" dietary pattern (P-trend = 0.06) and to frequent intake
      of hamburgers or hot dogs (adjusted prevalence ratio for at least once per week
      vs. never = 1.93; 95% CI = 1.03, 3.62), independent of total energy intake and
      other potential confounders. Time spent viewing television or playing outside the
      household were not significantly related to the prevalence of child overweight.
      In conclusion, child overweight in Bogota is more common than stunting and is
      associated with higher SES, maternal obesity, and a snacking dietary pattern.

PMID- 19106321
TI  - Transcript analysis of the selenoproteome indicates that dietary selenium
      requirements of rats based on selenium-regulated selenoprotein mRNA levels are
      uniformly less than those based on glutathione peroxidase activity.
AB  - Dietary selenium (Se) requirements in rats have been based largely upon
      glutathione peroxidase-1 (Gpx1) enzyme activity and Gpx1 mRNA levels can also be
      used to determine Se requirements. The identification of the complete
      selenoprotein proteome suggests that we might identify additional useful
      molecular biomarkers for assessment of Se status. To characterize Se regulation
      of the entire rat selenoproteome, weanling male rats were fed a Se-deficient diet
      (<0.01 microg Se/g) supplemented with graded levels of Se (0-0.8 microg/g diet)
      for 28 d, Se status was determined by tissue Se concentration and selenoenzyme
      activity, and selenoprotein mRNA abundance in liver, kidney, and muscle was
      determined by quantitative real-time-PCR. Tissue Se and selenoenzyme biomarkers
      indicated that minimal Se requirements were <or=0.1 microg Se/g diet for most
      biomarkers. Liver Gpx1 mRNA also decreased to <10% of Se-adequate levels, with a
      minimum Se requirement at 0.07 microg/g diet. Five selenoprotein mRNA in liver, 4
      in kidney, and 2 in muscle decreased to <41% of Se-adequate levels, all with
      minimum Se requirements at <or=0.07 microg/g diet; the majority of selenoprotein
      mRNA in each tissue were not significantly regulated by Se status, and 1
      selenoprotein, selenophosphate synthetase-2, was upregulated in Se-deficient
      kidney. Plateau breakpoints for all regulated selenoprotein mRNA were very
      similar, suggesting that 1 underlying mechanism is in play in Se regulation of
      selenoprotein mRNA. Lastly, we did not find any selenoprotein mRNA that could be
      used as biomarkers for super-nutritional/anticarcinogenic levels (up to 0.8
      microg Se/g diet) of Se.

PMID- 19106322
TI  - A randomized breast-feeding promotion intervention did not reduce child obesity
      in Belarus.
AB  - The evidence that breast-feeding protects against obesity is based on
      observational studies, with potential for confounding and selection bias. This
      article summarizes a previously published study in which we assessed whether an
      intervention designed to promote exclusive and prolonged breast-feeding affects
      children's height, weight, adiposity, and blood pressure (BP) at age 6.5 y. The
      Promotion of Breastfeeding Intervention Trial (PROBIT) is a cluster-randomized
      trial of a breast-feeding promotion intervention based on the WHO/UNICEF Baby
      Friendly Hospital Initiative. A total of 17,046 healthy breast-fed infants were
      enrolled from 31 Belarussian maternity hospitals and affiliated clinics, of whom
      13,889 (81.5%) were followed up at 6.5 y with duplicate measurements of height,
      weight, waist circumference, triceps and subscapular skinfold thicknesses,
      systolic and diastolic BP. Analysis was based on intention to treat, with
      statistical adjustment for clustering within hospitals/clinics to permit
      inferences at the individual level. The experimental intervention led to a large
      increase in exclusive breast-feeding at 3 mo (43.3% vs. 6.4%, P < 0.001) and a
      significantly higher prevalence of any breast-feeding throughout infancy. No
      significant intervention effects were observed on height, BMI, adiposity
      measures, or BP. The breast-feeding promotion intervention resulted in
      substantial increases in the duration and exclusivity of breast-feeding yet did
      not reduce measures of adiposity at age 6.5 y. Previous reports of protective
      effects against obesity may reflect uncontrolled bias caused by confounding and
      selection.

PMID- 19106323
TI  - Severe iron deficiency decreases both bone formation and bone resorption in rats.
AB  - The purpose of this study was to clarify the manner in which dietary iron
      deficiency decreased bone mineral density (BMD) in rats. Eighteen 3-wk-old male
      Wistar rats were divided into 3 groups of 6 rats each. The rats in 2 of the 3
      groups had free access to a control diet (C group) or an iron-deficient diet (ID
      group) for 4 wk. The rats in the third group (PF group) were pair-fed the control
      diet to the mean intake of the ID group. Compared with the C and PF groups,
      hematocrit and hemoglobin concentrations were significantly reduced and bone
      mineral content and BMD of the femur were significantly lower in the ID group.
      Bone histomorphometric parameters showed that the bone formation rate and
      osteoclast surface in the lumbar vertebra were significantly reduced in the ID
      group compared with the C and PF groups. Furthermore, dietary iron deficiency
      decreased serum 1,25-dihydroxycholecalciferol, insulin-like growth factor-I, and
      osteocalcin concentrations and urinary excretion of deoxypyridinoline. These
      results suggest that severe iron deficiency decreases not only bone formation but
      also bone resorption.

PMID- 19106325
TI  - Demographic, lifestyle, and health characteristics and serum B vitamin status are
      determinants of plasma total homocysteine concentration in the post-folic acid
      fortification period, 1999-2004.
AB  - Elevated circulating total homocysteine (tHcy) concentrations are related to
      increased risk for cardiovascular disease. Folic acid fortification resulted in a
      significant decrease in circulating tHcy in the United States. In the post-folic
      acid fortification period, associations between plasma tHcy and demographic,
      health, and lifestyle factors and B vitamin status were investigated. Data from
      the 3 recent NHANES cycles (1999-2004) were used to study the associations among
      plasma tHcy and sex, race/ethnicity, age, BMI, blood pressure (BP), serum
      creatinine, serum cotinine, vitamin/mineral supplement use, and folate and
      cobalamin status in 16,254 persons (8329 men, 7925 women). Multivariate-adjusted
      plasma tHcy was approximately 9.7% higher in men than in women (P < 0.0001),
      approximately 5.3% higher in non-Hispanic whites than in non-Hispanic blacks (P <
      0.0001), approximately 64.5% higher in individuals aged >or=60 y than in
      individuals aged <20 y (P < 0.0001), and approximately 5% higher in supplement
      nonusers than in supplement users (P < 0.0001). Persons in the 4th quartile for
      serum creatinine, serum cotinine, systolic BP, and serum methylmalonic acid (MMA)
      had approximately 36.1, approximately 13.4, approximately 5.6, and approximately
      16.2%, respectively, higher tHcy than those in the 1st quartile (P < 0.0001).
      Plasma tHcy was inversely associated with serum folate (P < 0.0001), RBC folate
      (P < 0.0001), and serum cobalamin (P < 0.0001). In the post-folic acid
      fortification period, sex, race/ethnicity, age, systolic BP, supplement use, RBC
      folate, and serum creatinine, cotinine, folate, and cobalamin are significant
      determinants of plasma tHcy. Serum MMA was strongly associated with plasma tHcy.

PMID- 19106324
TI  - 3T3-L1 adipocytes and rat adipose tissue have a high capacity for taurine
      synthesis by the cysteine dioxygenase/cysteinesulfinate decarboxylase and
      cysteamine dioxygenase pathways.
AB  - Taurine is the most abundant free amino acid in the body and is synthesized in
      mammals by 2 pathways. Taurine is synthesized either from the oxidation of
      cysteine via cysteine dioxygenase (CDO), which generates cysteinesulfinate that
      is decarboxylated by cysteinesulfinic acid decarboxylase (CSAD), or from the
      oxidation of cysteamine by cysteamine (2-aminoethanethiol) dioxygenase (ADO).
      Both pathways generate hypotaurine, which is oxidized to taurine. To determine
      whether these pathways for taurine synthesis are present in the adipocyte, we
      studied 3T3-L1 cells during their adipogenic conversion and fat from rats fed
      diets with varied sulfur-amino acid content. CDO, CSAD, and ADO protein levels
      increased during adipogenic differentiation of 3T3-L1 cells and all of these
      enzymes were significantly increased when cells achieved a mature adipocyte
      phenotype. Furthermore, these changes were accompanied by an increased
      hypotaurine and taurine production, particularly when cells were treated with
      cysteine or cysteamine. CDO mRNA levels also responded robustly to cysteine or
      cysteamine treatment in adipocytes but not in undifferentiated 3T3-L1 cells.
      Furthermore, CDO protein and activity were greater in adipose tissue from rats
      fed a high protein or cystine-supplemented low protein (LP) diet than in adipose
      tissue from rats fed a LP diet. Overall, our results demonstrate that CDO is
      regulated at both the level of enzyme abundance and the level of mRNA in mature
      adipocytes.

PMID- 19106326
TI  - Impact of infant feeding practices on childhood obesity.
AB  - Childhood obesity is a complex disease influenced by genetic and environmental
      factors and their interactions. The current surge in childhood obesity in the
      United States is attributable to an interaction between a genetic predisposition
      toward obesity and a permissive environment. Several recent systematic reviews
      and meta-analyses have been published on the association between breast-feeding
      and childhood obesity. In these analyses, adjustment for confounding factors
      attenuated or nullified the protective effect of breast-feeding on later obesity.
      The Viva La Familia Study was designed to identify genetic and environmental
      factors affecting obesity and its comorbidities in 1030 Hispanic children from
      319 families. Odds ratios for potential risk factors associated with childhood
      overweight were computed using binary logistic regression for panel data. Early
      infant-feeding practices were not significant. Salient independent risk factors
      for childhood obesity in this cohort of Hispanic children were age, birth weight,
      maternal obesity, paternal obesity, number of children in the family, and the
      percentage of awake time spent in sedentary activity. Breast-feeding may have a
      small protective effect against childhood obesity, although residual confounding
      may exist. Human milk is exquisitely fitted for optimal infant growth and
      development and may uniquely modulate neuroendocrine and immunologic pathways
      involved in the regulation of body weight. Nevertheless, other genetic and
      environmental determinants such as socioeconomic status, parental obesity,
      smoking, birth weight, and rapid infancy weight gain far supersede infant-feeding
      practices as risk factors for childhood obesity.

PMID- 19106327
TI  - Plasma adiponectin concentrations are associated with body composition and plant
      based dietary factors in female twins.
AB  - Circulating adiponectin is emerging as an important link between obesity, type 2
      diabetes, and cardiovascular disease (CVD). However, the spectrum of lifestyle
      factors that modulate the adiponectin concentration remains to be elucidated,
      particularly among women. We conducted a cross-sectional study of 877 female twin
      pairs from the TwinsUK adult twin registry. Using a co-twin design, we examined
      dietary and body composition influences on adiponectin by conducting matched,
      within-pair analyses to eliminate confounding. Following multivariable adjustment
      within-twin pairs, significant influences on adiponectin (log-transformed,
      percent change per SD of the dietary/body composition variable) were observed for
      nonstarch polysaccharides (3.25%; 95% CI: 0.06, 6.54; P < 0.05) and magnesium
      intake (3.80%; 95%CI: 0.17, 7.57; P < 0.05), with a trend toward an association
      for fruit and vegetable (F&V) intakes (2.55%; 95% CI: -0.26, 5.45; P = 0.08).
      These modest positive associations cannot be explained by confounding through
      other lifestyle factors shared by the twins. A significant relationship between
      adiponectin and 3 derived dietary patterns (F&V, dieting, traditional English),
      carbohydrate, protein, trans fat, and alcohol intake was also observed. Strong
      inverse associations with adiponectin were observed for BMI (-10.72%; 95% CI: 
      13.78, -7.55), total (-6.89%: 95% CI: -10.34, -3.30; P < 0.05), and central fat
      mass (-12.50%; 95% CI: -15.82, -9.05; P < 0.05); these relationships were
      significant both when twins were analyzed as individuals and when characteristics
      were contrasted within-twin pairs, suggesting a direct effect. We observed modest
      associations between dietary factors and adiponectin in female twins, independent
      of adiposity, and report strong inverse associations with body composition. These
      data reinforce the importance of weight maintenance and increasing consumption of
      diets rich in plant-based foods to prevent CVD and type 2 diabetes.

PMID- 19106329
TI  - Individual trans octadecenoic acids and partially hydrogenated vegetable oil
      differentially affect hepatic lipid and lipoprotein metabolism in golden Syrian
      hamsters.
AB  - Trans fatty acids (TFA) from industrial sources [i.e. partially hydrogenated
      vegetable oil (PHVO)] have been associated with several chronic human diseases,
      especially coronary heart disease (CHD). The possible contribution of individual
      TFA to overall CHD risk remains largely unknown. The objective of the present
      study was to investigate the effects of 2 major trans 18:1 isomers, trans-9 18:1
      [elaidic acid (EA)] and trans-11 18:1 [vaccenic acid (VA)] on plasma lipid
      biomarkers of CHD risk. Thirty-two male Golden Syrian hamsters were randomly
      assigned to 1 of 4 dietary treatments: 1) control "Western" diet; 2) PHVO
      supplement; 3) EA supplement; and 4) VA supplement. Fat supplements were
      incorporated into the respective treatment diets at 2.5 g/100 g of diet. Compared
      with the control diet, the PHVO diet increased the plasma ratios of total:HDL
      cholesterol and nonHDL:HDL-cholesterol by 17 and 23%, respectively. In contrast,
      these values decreased by 27 and 46% after the EA treatment and 8 and 14% after
      the VA treatment, respectively, indicating an improvement (reduction) in CHD
      risk. With regard to liver lipids, the EA diet reduced the content of (n-3) and
      (n-6) PUFA relative to the other treatments, suggesting an inhibition of enzymes
      common to the 2 biosynthesis pathways. Overall, results demonstrate that the
      hypercholesterolemic effects of PHVO are not dependent on the presence of EA or
      VA and that other bioactive components in PHVO must be responsible for its
      associated adverse health effects.

PMID- 19106328
TI  - Plasma 25-hydroxyvitamin d is associated with markers of the insulin resistant
      phenotype in nondiabetic adults.
AB  - We examined the cross-sectional association between plasma 25-hydroxyvitamin D
      [25(OH)D] and markers of the insulin resistant phenotype. Plasma 25(OH)D
      concentrations were measured in 808 nondiabetic participants of the Framingham
      Offspring Study. Outcome measures included fasting and 2-h post 75-g oral glucose
      tolerance test (OGTT) glucose and insulin; these were used to calculate the
      homeostatic model assessment-insulin resistance (HOMA-IR) and insulin sensitivity
      index (ISI(0,120)). We also measured plasma adiponectin, triacylglycerol, and HDL
      cholesterol concentrations as markers of the insulin-resistant phenotype. After
      adjusting for age, sex, BMI, waist circumference, and current smoking status,
      plasma 25(OH)D concentration was inversely associated with fasting plasma glucose
      and insulin concentrations, and HOMA-IR. Compared with the participants in the
      lowest tertile category of plasma 25(OH)D, those in the highest tertile category
      had a 1.6% lower concentration of fasting plasma glucose (P-trend = 0.007), 9.8%
      lower concentration of fasting plasma insulin (P-trend = 0.001), and 12.7% lower
      HOMA-IR score (P-trend < 0.001). After adjusting for age and sex, plasma 25(OH)D
      was positively associated with ISI(0,120), plasma adiponectin, and HDL
      cholesterol and inversely associated with plasma triacylglycerol, but these
      associations were no longer significant after further adjustment for BMI, waist
      circumference, and current smoking status. 25(OH)D and 2-h post-OGTT glucose were
      not associated. Among adults without diabetes, vitamin D status was inversely
      associated with surrogate fasting measures of insulin resistance. These results
      suggest that vitamin D status may be an important determinant for type 2 diabetes
      mellitus.

PMID- 19106330
TI  - Dietary trans-10, cis-12 conjugated linoleic acid reduces early glomerular
      enlargement and elevated renal cyclooxygenase-2 levels in young obese fa/fa
      zucker rats.
AB  - Conjugated linoleic acid (CLA) slows the progression of disease in models of
      chronic kidney disease. Because obesity is associated with nephropathy and
      increased renal cyclooxygenase (COX) levels, the effects of dietary CLA on kidney
      function, morphology, and COX protein levels in the kidneys of young obese
      (fa/fa) Zucker rats, a model of metabolic syndrome, were examined. In study 1, 6
      wk-old fa/fa and lean Zucker rats were given a mixture of CLA isomers (1.5% CLA,
      wt:wt) or the control diet (CTL) with no CLA for 8 wk. To examine specific isomer
      effects, study 2 used the same model with the following diets: 0.4% (g/g) cis-9,
      trans-11 (c9,t11) CLA; 0.4% trans-10, cis-12 (t10,c12) CLA; a combination of
      these 2 isomers (0.4% each); or CTL diets with no CLA. In study 1, fa/fa rats
      given the CLA mixture had 11% smaller kidney weights and 28% smaller glomeruli,
      and feed intake and body weight did not differ from the CTL rats. In study 2,
      diet also did not affect body weights, but fa/fa rats given a diet containing
      t10,c12 CLA had 7% lower kidney weights, 20% smaller glomeruli, and 39% lower COX
      2 protein levels than CTL rats. In conclusion, dietary t10,c12 CLA reduces the
      enlargement of glomeruli in young obesity-associated nephropathy and is
      associated with lower protein levels of renal COX-2. Long-term studies with CLA
      supplementation are required to determine whether these changes would lead to
      reduction in development of renal disease associated with obesity.

PMID- 19106333
TI  - New pharmacologic findings for the treatment of PONV and PDNV.
AB  - PURPOSE: Research regarding new pharmacologic findings in regards to the
      treatment of postoperative nausea and vomiting (PONV) and postdischarge nausea
      and vomiting (PDNV) are discussed. SUMMARY: PONV and PDNV have many important
      negative outcomes, including medical complications and financial consequences.
      Great strides in basic research have identified a plethora of mechanisms involved
      in regulating and processing the emetic reflex, and subsequent development of
      antiemetic treatments has lessened these burdens. The currently available
      antiemetic agents are not able to individually ameliorate PONV, so guidelines
      have been developed that recommend administering a combination of antiemetic
      treatments from different drug classes as prophylaxis, especially for high-risk
      patients. Recent research has indicated that due to the unique structural
      characteristics of palonosetron that impact receptor binding, this 5-HT(3)
      receptor antagonist has a pharmacokinetic and pharmacologic profile different
      from other inhibitors within the drug class. Implications of the high affinity,
      allosteric, and positive cooperative binding properties of palonosetron include
      longer and tighter binding to the 5-HT(3) receptor, making palonosetron a very
      efficient antagonist and less likely to be displaced by the binding of serotonin.
      CONCLUSION: Ongoing research is warranted in order to better prevent and manage
      PONV and PDNV.

PMID- 19106332
TI  - MEN epsilon/beta nuclear-retained non-coding RNAs are up-regulated upon muscle
      differentiation and are essential components of paraspeckles.
AB  - Studies of the transcriptional output of the human and mouse genomes have
      revealed that there are many more transcripts produced than can be accounted for
      by predicted protein-coding genes. Using a custom microarray, we have identified
      184 non-coding RNAs that exhibit more than twofold up- or down-regulation upon
      differentiation of C2C12 myoblasts into myotubes. Here, we focus on the Men
      epsilon/beta locus, which is up-regulated 3.3-fold during differentiation. Two
      non-coding RNA isoforms are produced from a single RNA polymerase II promoter,
      differing in the location of their 3' ends. Men epsilon is a 3.2-kb
      polyadenylated RNA, whereas Men beta is an approximately 20-kb transcript
      containing a genomically encoded poly(A)-rich tract at its 3'-end. The 3'-end of
      Men beta is generated by RNase P cleavage. The Men epsilon/beta transcripts are
      localized to nuclear paraspeckles and directly interact with NONO. Knockdown of
      MEN epsilon/beta expression results in the disruption of nuclear paraspeckles.
      Furthermore, the formation of paraspeckles, after release from transcriptional
      inhibition by DRB treatment, was suppressed in MEN epsilon/beta-depleted cells.
      Our findings indicate that the MEN epsilon/beta non-coding RNAs are essential
      structural/organizational components of paraspeckles.

PMID- 19106334
TI  - Current research on PONV/PDNV: Practical implications for today's pharmacist.
AB  - PURPOSE: Guidelines have been constructed to optimize the management of patients
      at risk of developing postoperative nausea and vomiting or postdischarge nausea
      and vomiting (PONV/PDNV), including the 2002 American Society of
      Anesthesiologists (ASA) recommendations, the 2006 guidelines assembled by an
      American Society of PeriAnesthesia Nurses task force (ASPAN), and another set
      published in 2007 with the support of the Society for Ambulatory Anesthesia
      (SAMBA). The recommendations set forth are reviewed. SUMMARY: Patient risk
      factors have been identified that are associated with higher incidences of PONV.
      For prophylaxis of PONV in high-risk patients, combinational and multimodal
      therapies with as many as three interventions, including a 5-HT(3)-based therapy
      and other antiemetic agents with different mechanisms of action, were advocated
      by guidelines and systematic reviews; specific pharmacotherapies and other
      interventions were recommended, as well as a treatment algorithm. The number of
      antiemetic agents prescribed should be appropriate for the individual's risk
      level, once again emphasizing the importance of patient risk stratification.
      Prophylaxis for PONV should be maintained throughout the period of risk.
      CONCLUSION: Evidence from the Prospective Observational Study of Treatments,
      Outcomes, and Patterns of Care study indicates that the use of guideline
      recommended PONV and PDNV prophylactic treatments leads to improved outcomes.

PMID- 19106335
TI  - Do current antiemetic practices result in positive patient outcomes? Results of a
      new study.
AB  - PURPOSE: The problem of perioperative nausea and vomiting (including
      postoperative and postdischarge nausea and vomiting [PONV/PDNV]) among people
      undergoing general anesthesia is discussed. SUMMARY: Nausea and vomiting are not
      limited to the postanesthesia care unit (PACU) or the hospital, but can persist
      long after the patient has been discharged and has returned home. This
      underscores the need for new antiemetic agents that not only offer greater
      efficacy and proven safety, but also provide an extended duration of action. The
      Prospective Observational Study of Treatments, Outcomes and Patterns of Care
      (POSTOP), was designed to assess the impact that current antiemetic practices
      have on patient outcomes in the postoperative and postdischarge settings. The
      investigation assessed the treatments, outcomes, and patterns of care for PONV
      and PDNV in high-risk patients over the course of 72 hours following surgery.
      Based on this observational study, despite the availability of current guidelines
      there is no current standard of care for managing PONV and PDNV. CONCLUSION:
      Increasing the adherence to guidelines and the rational use of prophylaxis based
      on patient stratification will reduce the incidence of PONV, as will the
      development of new antiemetic agents with greater efficacies and longer durations
      of action that can provide extended protection from nausea and vomiting
      throughout the 72-hour postsurgical period.

PMID- 19106336
TI  - FDA panel debates merits of next-generation opioid formulations.

PMID- 19106337
TI  - Tapentadol approved as pain reliever.

PMID- 19106338
TI  - World's drug supply chain needs better oversight, FDA says.

PMID- 19106341
TI  - Electronic prescribing in the ambulatory care setting.

PMID- 19106342
TI  - Bowel preparations for colonoscopy: a review.
AB  - PURPOSE: The mechanisms of action, clinical efficacy, tolerability, and safety of
      two major classes of bowel purgatives, poly-ethylene glycol- electrolyte lavage
      solutions (PEG-ELSs) and sodium phosphate preparations, are reviewed. SUMMARY:
      PEG-ELSs are osmotically balanced preparations that promote bowel cleansing
      through the ingestion of nonabsorbable fluid. Sodium phosphate preparations are
      hyperosmotic purgatives that promote bowel cleansing by osmotically drawing fluid
      into the bowel lumen for evacuation. Studies suggest that 2-L PEG-ELS regimens
      are generally as effective as and more tolerable than full-volume PEG-ELS
      preparations. Studies have also found that sodium phosphate tablets may provide a
      more tolerable alternative to PEG-ELS regimens and traditional sodium phosphate
      products without compromising bowel cleansing efficacy. Proper renal function
      plays a particularly important role in avoiding potential safety issues related
      to sodium phosphate-induced shifts in the fluid and electrolyte balance.
      Preventing dehydration in patients undergoing bowel preparation can prevent
      severe adverse events, regardless of the purgative administered. Optimizing the
      process of bowel preparation involves administering proper purgative choices in
      appropriate patient populations. Moreover, patient education and compliance with
      preparation instructions, including correct dosing and adequate hydration, may
      reduce the risk of adverse events and serious complications. CONCLUSION: Although
      next-generation PEG-ELS and sodium phosphate products are well tolerated and
      preferred by patients over traditional bowel preparation regimens, safety issues
      remain a concern for both purgative classes. Sodium phosphate preparations are
      generally more effective and better tolerated than PEG-ELS formulations but
      should be administered with caution in patients with preexisting or at an
      increased risk for electrolyte disturbances.

PMID- 19106343
TI  - Development of computerized alerts with management strategies for 25 serious drug
      drug interactions.
AB  - PURPOSE: The development of computerized alerts with management strategies for 25
      drug-drug interactions (DDIs) is described. SUMMARY: To ensure that clinicians,
      when confronted with any of 25 serious DDIs in the ambulatory care setting, can
      avoid these DDIs while treating patients with appropriate medications, management
      strategies were developed using a consensus approach. Several methods were used
      to ensure that the recommended alternatives were truly safe. Four well
      established drug-interaction compendia were screened, and any potential
      alternative agent that was listed as having an interaction (moderate or serious
      in nature) was excluded from the list of alternative agents. Case reports, case
      series, and clinical studies that focused on the alternative combinations were
      reviewed to determine if the alternative posed interaction risks. If an
      interaction for the alternative combination had not been identified in the
      compendia or in the literature search, other potential mechanisms for drug
      interactions were explored such as alterations in absorption, distribution,
      metabolism, or excretion. Pharmacology and therapeutics textbooks and other drug
      information sources also served as resources. In general, the strategies included
      alternatives to both medications, changing dosage or increasing monitoring of one
      of the agents, situations where one of the medications had no alternative but
      alternatives were available for the other medication, and alternative methods of
      birth control. In some situations the two drugs were contraindicated, while in
      others the two drugs should be avoided if at all possible and alternatives used.
      CONCLUSION: Consensus-based management strategies for 25 serious DDIs were
      developed for inclusion in computerized alert messages.

PMID- 19106344
TI  - Managing severe sepsis: a national survey of current practices.
AB  - PURPOSE: Current practices for managing severe sepsis in U.S. hospitals were
      studied. METHODS: A questionnaire was distributed to nurse managers who were
      members of the Association of Critical Care Nurses to assess current practices
      associated with the management of severe sepsis, including assessment of sepsis
      management priority, patient identification and screening process for sepsis,
      current treatment practices, process measures and outcomes measurements, and
      hospital demographics. Differences among small (<200 beds), medium (200-399
      beds), and large (>/=400 beds) hospitals were identified using chi-square
      analysis and Student's t test. RESULTS: A total of 414 surveys were completed,
      received, and analyzed. As hospital bed size increased, so did the percentage of
      hospitals with an active severe sepsis program (p = 0.002). Hospitals rated the
      effect of severe sepsis on mortality as the paramount issue influencing severe
      sepsis prioritization. Screening for severe sepsis most commonly occurred upon
      deterioration of laboratory test values, regardless of hospital size. Of 17
      Surviving Sepsis Campaign (SSC) treatment guidelines, hospitals most frequently
      reported adherence to ordering cultures within 6 hours of onset of acute organ
      dysfunction (71.3%). The least followed guideline was initiation of drotrecogin
      alfa (activated) within 24 hours of acute organ dysfunction (37.9%). CONCLUSION:
      A survey of critical care nurses revealed that of the 17 SSC treatment
      guidelines, hospitals most frequently reported adherence to those concerning
      prompt ordering of cultures, prompt administration of broad-spectrum antibiotics,
      and prompt initiation of deep venous thrombosis prophylaxis. Deterioration of
      laboratory test values was the most common identifier of severe sepsis,
      regardless of hospital size. Among all hospitals, the least followed guideline
      was prompt initiation of drotrecogin alfa (activated) therapy.

PMID- 19106345
TI  - Assessment of and recommendations to improve pharmacy faculty satisfaction and
      retention.
AB  - PURPOSE: The level of job satisfaction and items associated with job satisfaction
      are examined among pharmacy faculty in the United States. METHODS: An Internet
      based survey was developed and distributed via e-mail to randomly selected
      faculty. The survey questionnaire was developed based on items used in previous
      surveys related to faculty job satisfaction and included a seven-item job
      satisfaction measure, satisfaction with work- and career-related items, items
      regarding the work environment, and demographic information. Analysis of variance
      and Pearson's correlation coefficient were used to analyze the relationship among
      variables. RESULTS: Out of 1000 faculty members who received the survey, 266
      responded. The mean +/- S.D. level of global job satisfaction for faculty was
      3.82 +/- 0.77. Global satisfaction and salary satisfaction were associated with
      higher salary level (p < 0.001). Low-to-moderate levels of satisfaction were
      found for several work and career items. Female faculty members were less
      satisfied with time for family and personal needs compared with male faculty (p <
      0.001). Pharmacy practice faculty members were significantly more satisfied with
      working in an intellectually challenging environment compared with nonpharmacy
      practice faculty (p < 0.001). CONCLUSION: Although pharmacy faculty members
      experience moderate levels of job satisfaction, there are several work and career
      and work environment areas in which improvement in satisfaction is needed.
      Provision of competitive salaries and development of a stimulating, supportive
      institutional culture may increase job satisfaction and facilitate improved
      faculty retention.

PMID- 19106346
TI  - Frequency of incomplete medication histories obtained at triage.
AB  - PURPOSE: The frequency of incomplete medication histories obtained at triage in
      an emergency department (ED) is described. METHODS: The survey of medication
      histories collected during ED triage was conducted during a 20-week period. Data
      collection occurred on weekdays during the dayshift for 15 hours per week for a
      total of 300 hours. Patients who bypassed triage or were unconscious, unable to
      communicate, uncooperative, or violent were excluded. Ten student pharmacists
      were trained on study procedures and collected data using a data collection tool
      which included patient's chief complaints, medications and dosages, and whether
      medications were identified at triage. Patients' medication-related ED visits
      were classified as being caused by adverse effects, medication errors, poor
      adherence, intentional overdose, or therapeutic failure. RESULTS: During the 300
      hours of data collection, 2063 patients were admitted to the ED. Of these, 1465
      (71%) were interviewed and evaluated for complete medication histories. Among
      1172 (80%) patients identified as taking medications, the history obtained at
      triage failed to identify at least one medication in 707 (48%) patients. In cases
      where medications were not identified, a mixture of prescription (73%) and
      nonprescription (27%) medications were missed with a median of 2 drugs (range, 1
      20 drugs). Drugs missed at triage were related to the patient's chief complaint
      in 27% of the cases. CONCLUSION: Medication histories collected at triage in the
      ED of an urban medical center were often incomplete, especially among patients
      taking multiple medications. Efforts should be taken to improve methods for
      obtaining more complete medication histories during triage and collecting
      supplemental medication histories to ensure appropriate emergency care.

PMID- 19106347
TI  - Overview of biostatistics used in clinical research.
AB  - PURPOSE: A brief overview is given of the types of statistical tests that are
      available to analyze pharmacy research data. SUMMARY: The most important aspect
      of selecting the correct statistical test is defining the types of variables
      being analyzed. Variables that are controlled or determined by the researcher are
      referred to as independent variables. Dependent variables are those that are
      observed and are out of the researcher's control. There are two types of random
      error that exist with inferential statistics: rejecting a null hypothesis (H(0))
      when it is true and failing to reject H(0) when it is false. There are two
      primary ways to interpret the significance of results from an inferential
      statistical test: (1) creation of a confidence interval and determination of
      whether a value falls within the interval and (2) calculation of a ratio and
      determination of whether the resultant value exceeds an established critical
      value. Student's t test is one of the simplest inferential tests and can be used
      to illustrate both the confidence interval and the ratio approaches to evaluating
      sample data. The p value indicates the amount of error that can exist if the
      researcher chooses to reject H(0). Parametric tests require two additional
      assumptions in order to be applied correctly. Some examples of these include the
      two-sample t test and the paired t test. Nonparametric tests are designed for
      small sample sizes and are easy to calculate. These tests use the median as the
      measure of center. Some examples of nonparametric tests include the chi-square
      test and the Fisher exact test. Other statistical tests that are available to
      help the pharmacist researcher include equivalency testing, survival statistics,
      and noninferiority studies. CONCLUSION: Selection of the proper statistical test
      depends on the type and number of variables and whether parametric conditions are
      met.

PMID- 19106348
TI  - Therapeutic monitoring of vancomycin in adult patients: a consensus review of the
      American Society of Health-System Pharmacists, the Infectious Diseases Society of
      America, and the Society of Infectious Diseases Pharmacists.

PMID- 19106349
TI  - Three-dimensional ultrasonography of the fetal vermis at 18 to 26 weeks'
      gestation: time of appearance of the primary fissure.
AB  - OBJECTIVE: The purpose of this study was to establish the normality of the fetal
      vermis, ie, the time of appearance of the primary fissure, as well as its
      measurements between 18 and 26 weeks' gestation, using 3-dimensional (3D)
      ultrasonography. METHODS: A prospective cross-sectional study of normal singleton
      pregnancies was conducted. Examinations were performed with high-resolution
      transabdominal ultrasonography using the axial plane in 173 fetuses between 18
      and 26 weeks' gestation. Postprocessing measurements of the fetal vermis were
      done with 4-dimensional software using static volume contrast imaging and
      tomographic ultrasound imaging in the C-plane. Detection of the primary fissure
      was evaluated in all cases, and the time of appearance was documented. RESULTS:
      Adequate vermis measurements were obtained in 173 fetuses. Vermian length as a
      function of gestational age was expressed by regression equations, and the
      correlation coefficients were found to be highly statistically significant (P <
      .001). The normal mean +/- 2 SD for each gestational week was defined. The
      primary fissure was observed at 24 weeks' gestation in all cases, at 22 weeks in
      94% of cases, and as early as 18 weeks in 40%. CONCLUSIONS: This 3D study
      documents the appearance of the primary fissure and presents the normal range of
      vermian measurements, confirming normal development of the fetal vermis starting
      as early as 18 weeks' gestation. It also shows an easy method for visualizing the
      vermis with 3D ultrasonography at every gestational week regardless of fetal
      presentation.

PMID- 19106350
TI  - Aorta larger than pulmonary artery in the fetal 3-vessel view.
AB  - OBJECTIVE: Fetal great artery asymmetry may accompany congenital heart disease.
      The fetal echocardiographic 3-vessel view (3VV) allows assessment of the superior
      vena cava, ascending aorta (AA), and main pulmonary artery (MPA). Our aim was to
      determine the association of congenital heart disease in fetuses with an AA/MPA
      ratio of greater than 1. METHODS: We electronically searched our fetal
      echocardiographic database for studies performed between March 2002 and January
      2008 that showed 3VVs with AA/MPA ratios of greater than 1 and correlated the
      findings with the presence of congenital heart disease. RESULTS: In 2797 fetal
      echocardiograms, we identified 31 fetuses with normal 4-chamber views showing
      AA/MPA ratios of greater than 1 in the 3VV. Of 31 fetuses, 25 (81%) had tetralogy
      of Fallot (ToF) or a ToF variant, and 6 (19%) had an aortic valve abnormality or
      isolated dilatation of the AA. CONCLUSIONS: Screening obstetric fetal sonography
      showing a 3VV AA/MPA ratio of greater than 1 suggests congenital heart disease
      and indicates the need for comprehensive fetal echocardiography.

PMID- 19106351
TI  - High fetal splenic artery peak velocity in fetuses with hemoglobin Bart disease:
      a preliminary study.
AB  - OBJECTIVE: The purpose of this study was to evaluate the role of the splenic
      artery (SPA) peak systolic velocity (PSV) in identifying fetuses with hemoglobin
      (Hb) Bart disease among pregnancies at risk for the disease. METHODS: Pregnancies
      at risk for fetal Hb Bart disease scheduled for cordocentesis at 18 to 25 weeks'
      gestation at Maharaj Nakorn Chiang Mai Hospital were recruited into the study.
      The SPA PSV was measured before cordocentesis, and the final fetal diagnosis of
      Hb Bart disease was based on fetal Hb typing using high-performance liquid
      chromatography. RESULTS: Seventy-six singleton pregnancies at risk for fetal Hb
      Bart disease were sonographically evaluated for the SPA PSV and underwent
      cordocentesis for fetal blood analysis. Among the 76 recruited pregnancies, 17
      fetuses with Hb Bart disease were finally diagnosed by fetal blood analysis with
      high-performance liquid chromatography, and the remainder had no abnormalities or
      had the alpha-thalassemia 1 trait and were defined as unaffected fetuses. The
      mean SPA PSVs +/- SD for the unaffected and affected fetuses were significantly
      different: 21.17 +/- 3.7 cm/s (range, 13.8-29.9 cm/s) and 26.12 +/- 3.6 cm/s
      (range, 20.4-31.5 cm/s) respectively. The SPA PSV of the affected fetuses was
      higher than that of the unaffected ones (Wilcoxon signed rank test, P < .001).
      CONCLUSIONS: Splenic artery PSV assessment at mid pregnancy may have a potential
      role in identifying fetuses with Hb Bart disease. Further studies to evaluate the
      effectiveness of the SPA PSV in differentiating affected from unaffected fetuses
      among pregnancies at risk are desirable.

PMID- 19106352
TI  - Reliability of fetal middle cerebral artery velocity measurements: a randomized
      controlled trial of sonographer training.
AB  - OBJECTIVE: The purpose of this study was to determine the reliability of fetal
      middle cerebral artery (MCA) peak systolic velocity (PSV) measurements at a
      tertiary care center and to evaluate the effect of targeted training for
      sonographers. METHODS: Six sonographers were randomized to training modules for
      fetal MCA PSV or amniotic fluid volume (AFV) measurements. Six fetuses of
      uncomplicated pregnancies were selected for participation. Middle cerebral artery
      and AFV measurements were obtained before and after a training module. The
      intraobserver and interobserver variability (reliability) was calculated with
      intraclass correlation coefficients and was compared between groups. RESULTS:
      Administration of the MCA training module increased the number of technically
      adequate MCA images obtained (odds ratio, 3.95; 95% confidence interval, 1.07
      14.65). The intraobserver and inter-observer variability for MCA measurements was
      significantly reduced after the targeted training module (P = .05). CONCLUSIONS:
      The reliability of fetal MCA PSV measurements improved after a targeted training
      program.

PMID- 19106353
TI  - Supratentorial abnormalities in the Chiari II malformation, II: tectal
      morphologic changes.
AB  - OBJECTIVE: The sonographic diagnosis of fetal myelomeningocele has improved
      mainly because the diagnostic focus has shifted from observation of spinal
      manifestations to observation of cranial abnormalities. Intracranial diagnostic
      criteria rely on abnormalities in the posterior fossa. We describe abnormalities
      in tectal morphologic characteristics that, although well described on magnetic
      resonance imaging, have received little attention in the sonographic literature.
      This study analyzed the frequency of this observation and technical aspects that
      improve its visualization. METHODS: From a database of obstetric sonograms, we
      identified all cases of sonographically detected myelomeningocele. The search
      covered the years 1999 to 2007. We retrospectively reviewed the fetal
      intracranial findings with special attention to elongation or "beaking" of the
      tectum. RESULTS: A total of 89 fetuses were identified. The mean and median
      gestational ages were 22 weeks 4 days and 22 weeks 2 days, respectively. Of the
      89 cases, 59 (66%) had an abnormal tectal shape. The abnormality was seen in 77%
      of cases judged to be suboptimally visualized and 62% of cases with good
      visualization. Tectal abnormalities were seen equally well in fetuses before and
      after 24 weeks. Finally, tectal abnormalities were seen more frequently as the
      severity of posterior fossa findings increased. CONCLUSIONS: Tectal morphologic
      alteration is a common supratentorial feature of the Chiari II malformation on
      prenatal sonography both before and after 24 weeks' gestation. Its frequency
      increases with the severity of posterior fossa abnormalities. Therefore, it may
      be useful as a supratentorial indicator of both the presence and, potentially,
      the severity of the Chiari II malformation.

PMID- 19106354
TI  - Sonographic findings in trisomy 9.
AB  - OBJECTIVE: The purpose of this study was to identify the most common prenatal
      sonographic findings in fetuses with complete trisomy 9. METHODS: A retrospective
      review of all cases of trisomy 9 at 5 participating institutions over a 15-year
      interval was conducted. Indications for referral and sonographic findings in each
      case were reviewed to identify characteristic fetal structural anomalies.
      RESULTS: Six cases of trisomy 9 are presented. Most patients were referred for
      abnormal sonographic findings on screening examinations (66%) or advanced
      maternal age (33%). Fetal heart defects and central nervous system malformations
      were the most frequent sonographic anomalies seen. CONCLUSIONS: Sonographic
      findings in trisomy 9 are similar to those found in other autosomal trisomies.
      Because trisomy 9 is uniformly lethal and is not included as part of the standard
      prenatal aneuploidy screening by fluorescence in situ hybridization analysis,
      clinicians should be cautious in counseling patients with structurally abnormal
      fetuses until the full karyotype is available.

PMID- 19106355
TI  - Sonographic measurements of the thymus in male and female fetuses.
AB  - OBJECTIVE: The purpose of this study was to determine whether the size of the
      thymus is different in male and female fetuses. METHODS: In this prospective
      study, the transverse diameter and perimeter of the thymus were measured in
      healthy fetuses between 24 and 37 weeks' gestation. The means of the study
      variables from male and female fetuses were compared by the Student t test, and
      the relationships between the transverse diameter and perimeter of the thymus and
      gestational age and other common fetal biometric parameters were determined by
      linear regression modeling. RESULTS: No differences were noted between male and
      female fetuses for the means of the study variables. After the relationship
      between the transverse diameter and perimeter of the thymus and gestational age
      was confirmed (R(2) = 0.8 and 0.75, respectively; both P < .01), the 95%
      confidence interval-predicted changes were calculated, and the scatterplots of
      the measurements suggested that sex did not affect the size of the thymus. Bland
      Altman plots were used to analyze intraobserver variability and showed good
      agreement for both of these thymic measurements for male and female fetuses.
      CONCLUSIONS: These results suggest that fetal sex does not affect the size of the
      thymus and, together with previous reports, support the hypothesis that a
      quantitative reduction in fetal thymus size could serve as an indirect marker of
      abnormal thymopoiesis and congenital thymic insufficiency.

PMID- 19106356
TI  - A Thai reference for normal fetal nasal bone length at 15 to 23 weeks' gestation.
AB  - OBJECTIVE: The purpose of this study was to establish a Thai reference for normal
      fetal nasal bone length at 15 to 23 weeks' gestation. METHODS: The fetal nasal
      bone was measured by sonography in 295 pregnant women at 15 to 23 weeks'
      gestation from May to August 2005. One of the first 4 authors performed 3
      measurements for each woman when the fetus was in the midsagittal plane and the
      nasal bone was close to a 45 degrees or 135 degrees angle to the ultrasound beam.
      All neonates were examined after delivery to confirm an absence of congenital
      abnormalities. RESULTS: The median nasal bone length increased by gestational age
      from 3.6 mm at 15 weeks to 7.3 mm at 23 weeks in a linear relationship. The fifth
      percentile nasal bone lengths were 2.5, 3.04, 3.28, 3.64, 4.21, 4.82, 5.69, and
      6.13 mm at 15, 16, 17, 18, 19, 20, 21, and 22 weeks, respectively. The median
      time for measurement was 5 minutes. CONCLUSIONS: The nasal bone length in Thai
      fetuses at 15 to 23 weeks was found to be on average shorter than that in white
      and African American fetuses.

PMID- 19106357
TI  - Serial transvaginal sonographic findings of cervical ectopic pregnancy treated
      with high-dose methotrexate.
AB  - OBJECTIVE: We analyzed transvaginal sonographic findings from patients with
      cervical ectopic pregnancies treated with high-dose methotrexate (MTX). METHODS:
      This was a retrospective analysis of cervical pregnancies diagnosed in our
      institution from 1996 through 2006. We divided the cases into an MTX treatment
      group and a surgical treatment group. We included cases treated with high-dose
      MTX alone. We analyzed 9 cervical ectopic pregnancies treated with MTX, which was
      injected intravascularly at 100 mg/m(2) plus 200 mg/m(2) in 500 mL of a normal
      saline solution with folinic acid rescue. The gestational sac sizes and serum
      human chorionic gonadotropin (hCG) levels were periodically monitored to
      determine the resolution status. RESULTS: Fifty cervical pregnancies were
      diagnosed during the study period. Thirty cases were treated with MTX, and 20
      were treated with surgical procedures. Among the 30 cases in the MTX treatment
      group, 9 had high-dose MTX injection without surgical procedures. Cervical mass
      regression appeared at a median of 40 (range, 10-88) days after treatment,
      whereas the serum hCG level decreased at a median of 14 (range, 9-17) days after
      treatment. The median time to complete regression of the cervical mass was 86
      (range, 48-141) days, and the median time to complete regression of the serum hCG
      level was 68 (range, 19-143) days. Cervical pregnancy was noted as a gestational
      sac at first but coexisted with a mixed echoic lesion 19 days after treatment. At
      33 days after treatment, the cervical pregnancy was completely replaced by the
      mixed echoic lesion. CONCLUSIONS: Resolution of the cervical mass on sonography
      lagged far behind resolution of the serum hCG level. The cervical mass evolved
      from a gestational sac into a mixed echoic lesion on serial transvaginal
      sonography.

PMID- 19106358
TI  - Vaginal abscess mimicking a cystocele and causing voiding dysfunction after Burch
      colposuspension.

PMID- 19106359
TI  - Antenatal diagnosis and treatment of a dyshormonogenetic fetal goiter.

PMID- 19106360
TI  - Unusual prenatal sonographic findings of epidermolysis bullosa mimicking an
      amniotic band constriction ring.

PMID- 19106361
TI  - Extra-amniotic pregnancy with fetal gastroschisis and clubfoot.

PMID- 19106362
TI  - Focal foveolar hyperplasia in an infant: color Doppler sonographic findings.

PMID- 19106363
TI  - Testosterone-secreting mature ovarian teratoma causing severe virilization in an
      adolescent: sonographic and color Doppler characteristics.

PMID- 19106364
TI  - Perinatal imaging in bronchopulmonary sequestration.

PMID- 19106365
TI  - Is 3-dimensional sonography useful in the prenatal diagnosis of ambiguous
      genitalia?

PMID- 19106366
TI  - "Brothers in arms": 3-dimensional sonographic findings in a first-trimester
      thoraco-omphalopagus conjoined twin pair.

PMID- 19106367
TI  - Sonographically guided extracorporeal ablation of uterine fibroids with high
      intensity focused ultrasound: midterm results.

PMID- 19106368
TI  - AIUM practice guideline for the performance of a breast ultrasound examination.

PMID- 19106369
TI  - AIUM practice guideline for documentation of an ultrasound examination.

PMID- 19106370
TI  - AIUM practice guideline for the performance of an ultrasound examination for
      detection and assessment of developmental dysplasia of the hip.

PMID- 19106371
TI  - AIUM practice guideline for the performance of renal artery duplex sonography.

PMID- 19106372
TI  - AIUM practice guideline for ultrasonography in reproductive medicine.

PMID- 19106373
TI  - Phosphate-deprived roots are hypersensitive to auxin.

PMID- 19106374
TI  - Lotus japonicus CASTOR and POLLUX are ion channels essential for perinuclear
      calcium spiking in legume root endosymbiosis.
AB  - The mechanism underlying perinuclear calcium spiking induced during legume root
      endosymbioses is largely unknown. Lotus japonicus symbiosis-defective castor and
      pollux mutants are impaired in perinuclear calcium spiking. Homology modeling
      suggested that the related proteins CASTOR and POLLUX might be ion channels.
      Here, we show that CASTOR and POLLUX form two independent homocomplexes in
      planta. CASTOR reconstituted in planar lipid bilayers exhibited ion channel
      activity, and the channel characteristics were altered in a symbiosis-defective
      mutant carrying an amino acid replacement close to the selectivity filter.
      Permeability ratio determination and competition experiments reveled a weak
      preference of CASTOR for cations such as potassium over anions. POLLUX has an
      identical selectivity filter region and complemented a potassium transport
      deficient yeast mutant, suggesting that POLLUX is also a potassium-permeable
      channel. Immunogold labeling localized the endogenous CASTOR protein to the
      nuclear envelope of Lotus root cells. Our data are consistent with a role of
      CASTOR and POLLUX in modulating the nuclear envelope membrane potential. They
      could either trigger the opening of calcium release channels or compensate the
      charge release during the calcium efflux as counter ion channels.

PMID- 19106375
TI  - Phosphate availability alters lateral root development in Arabidopsis by
      modulating auxin sensitivity via a mechanism involving the TIR1 auxin receptor.
AB  - The survival of plants, as sessile organisms, depends on a series of
      postembryonic developmental events that determine the final architecture of
      plants and allow them to contend with a continuously changing environment.
      Modulation of cell differentiation and organ formation by environmental signals
      has not been studied in detail. Here, we report that alterations in the pattern
      of lateral root (LR) formation and emergence in response to phosphate (Pi)
      availability is mediated by changes in auxin sensitivity in Arabidopsis thaliana
      roots. These changes alter the expression of auxin-responsive genes and stimulate
      pericycle cells to proliferate. Modulation of auxin sensitivity by Pi was found
      to depend on the auxin receptor TRANSPORT INHIBITOR RESPONSE1 (TIR1) and the
      transcription factor AUXIN RESPONSE FACTOR19 (ARF19). We determined that Pi
      deprivation increases the expression of TIR1 in Arabidopsis seedlings and causes
      AUXIN/INDOLE-3-ACETIC ACID (AUX/IAA) auxin response repressors to be degraded.
      Based on our results, we propose a model in which auxin sensitivity is enhanced
      in Pi-deprived plants by an increased expression of TIR1, which accelerates the
      degradation of AUX/IAA proteins, thereby unshackling ARF transcription factors
      that activate/repress genes involved in LR formation and emergence.

PMID- 19106377
TI  - Reduced 10-year risk of coronary heart disease in patients who participated in a
      community-based diabetes prevention program: the DEPLOY pilot study.
AB  - OBJECTIVE: We evaluated whether participation in a community-based group diabetes
      prevention program might lead to relative changes in composite 10-year coronary
      heart disease (CHD) risk for overweight adults with abnormal glucose metabolism.
      RESEARCH DESIGN AND METHODS: We used the UK Prospective Diabetes Study engine to
      estimate CHD risk for group-lifestyle and brief counseling (control) groups.
      Between-group risk changes after 4 and 12 months were compared using ANCOVA.
      RESULTS: Baseline 10-year risk was similar between treatment groups (P = 0.667).
      At 4 and 12 months, the intervention group experienced significant decreases in
      10-year risk from baseline (-3.28%, P < 0.001; and -2.23%, P = 0.037) compared
      with control subjects (-0.78%, P = 0.339; and +1.88%, P = 0.073). Between-group
      differences were statistically significant and increased from the 4- to 12-month
      visits. CONCLUSIONS: Community-based delivery of the Diabetes Prevention Program
      lifestyle intervention could be a promising strategy to prevent both CHD and type
      2 diabetes in adults with pre-diabetes.

PMID- 19106376
TI  - A tobacco calcium-dependent protein kinase, CDPK1, regulates the transcription
      factor REPRESSION OF SHOOT GROWTH in response to gibberellins.
AB  - The homeostasis of gibberellins (GAs) is maintained by negative feedback in
      plants. REPRESSION OF SHOOT GROWTH (RSG) is a tobacco (Nicotiana tabacum)
      transcriptional activator that has been suggested to play a role in GA feedback
      by the regulation of GA biosynthetic enzymes. The 14-3-3 signaling proteins
      negatively regulate RSG by sequestering it in the cytoplasm in response to GAs.
      The phosphorylation on Ser-114 of RSG is essential for 14-3-3 binding of RSG.
      Here, we identified tobacco Ca(2+)-dependent protein kinase (CDPK1) as an RSG
      kinase that promotes 14-3-3 binding to RSG by phosphorylation of Ser-114 of RSG.
      CDPK1 interacts with RSG in a Ca(2+)-dependent manner in vivo and in vitro and
      specifically phosphorylates Ser-114 of RSG. Inhibition of CDPK repressed the GA
      induced phosphorylation of Ser-114 of RSG and the GA-induced nuclear export of
      RSG. Overexpression of CDPK1 inhibited the feedback regulation of a GA 20-oxidase
      gene and resulted in sensitization to the GA biosynthetic inhibitor. Our results
      suggest that CDPK1 decodes the Ca(2+) signal produced by GAs and regulates the
      intracellular localization of RSG.

PMID- 19106378
TI  - Association between metabolic syndrome and depressive symptoms in middle-aged
      adults: results from the Whitehall II study.
AB  - OBJECTIVE: Although it is possible that the association between depression and
      the metabolic syndrome is a "two-way street," the metabolic syndrome as a
      predictor of depression has been little investigated. We examined whether the
      metabolic syndrome is associated with the onset of depressive symptoms in a
      cohort of middle-aged British civil servants. RESEARCH DESIGN AND METHODS:
      Analyses included 5,232 participants (41-61 years of age) from the Whitehall II
      prospective cohort study. Depressive symptoms were assessed in 1991-1993 and
      again 6 years later using the depression subscale from the 30-item General Health
      Questionnaire. Metabolic syndrome was assessed in 1991-1993, according to
      National Cholesterol Education Program criteria. RESULTS: Presence of the
      metabolic syndrome was associated with an increased risk of future depressive
      symptoms, odds ratio 1.38 (95% CI 1.02-1.96) after adjustment for potential
      confounders. Of the five components, only central obesity, high triglyceride
      levels, and low HDL cholesterol levels predicted depressive symptoms. These
      components explained most of the association between the metabolic syndrome and
      the onset of depressive symptoms. CONCLUSIONS: Our results suggest that the
      metabolic syndrome, in particular the obesity and dyslipidemia components, is
      predictive of depressive symptoms.

PMID- 19106379
TI  - Population intermediate outcomes of diabetes under pay-for-performance incentives
      in England from 2004 to 2008.
AB  - OBJECTIVE: To evaluate diabetes outcomes under a national "pay-for-performance"
      program. RESEARCH DESIGN AND METHODS: Data were analyzed for 98% of all English
      family practices. For each practice, the proportion of diabetic subjects with A1C
      <or=7.5%, blood pressure <or=145/85 mmHg, and cholesterol <or=5 mmol/l was
      determined. Practices achieving less than the 25th centile for the A1C target for
      2006-2007 were classified as low performing. RESULTS: The proportion achieving
      the A1C target at the median practice increased from 59.1% (interquartile range
      [IQR] 51.7-65.9) in 2004-2005 to 66.7% (IQR 60.6-72.7) in 2007-2008, blood
      pressure from 70.9% in 2004-2005 to 80.2% in 2007-2008, and cholesterol from
      72.6% in 2004-2005 to 83.6% in 2007-2008. In 2004-2005, 57% of practices were low
      performing (range by region 42.4-69.9). In 2007-2008, 26% of practices were low
      performing (range 11.6-37.5). CONCLUSIONS: Introduction of pay-for-performance
      may be one factor contributing to increasing achievement of targets and reducing
      problems of low performance.

PMID- 19106380
TI  - Comparison of glycemic variability associated with insulin glargine and
      intermediate-acting insulin when used as the basal component of multiple daily
      injections for adolescents with type 1 diabetes.
AB  - OBJECTIVE: To compare the glucose variability associated with insulin glargine
      and NPH/Lente insulin used as the basal insulin component of a multiple daily
      injection (MDI) regimen in pediatric patients with type 1 diabetes. RESEARCH
      DESIGN AND METHODS: Continuous glucose monitoring data were collected from a
      subset of patients (n = 90) who agreed to use a continuous glucose monitoring
      system during an active-controlled, randomized, open-label study evaluating the
      safety and efficacy of insulin glargine and NPH/Lente insulin used with insulin
      lispro as part of an MDI regimen. RESULTS: Treatment with insulin glargine
      resulted in significant reductions in glucose variability as measured by the SD
      of glucose values (adjusted mean change from baseline to week 24: -13.4 mg/dl [
      0.74 mmol/l]; P <or= 0.05), mean amplitude of glycemic excursion (-34.4 mg/dl [
      1.91 mmol/l]; P <or= 0.0001), and M value (-9.6 mg/dl [-0.53 mmol/l]; P <or=
      0.03). The corresponding reductions in glucose variability for NPH/Lente were not
      significant. CONCLUSIONS: Insulin glargine is associated with greater reductions
      in glucose variability than NPH/Lente insulin in pediatric patients with type 1
      diabetes.

PMID- 19106381
TI  - Decline in physical fitness from childhood to adulthood associated with increased
      obesity and insulin resistance in adults.
AB  - OBJECTIVE: To examine how fitness in both childhood and adulthood is associated
      with adult obesity and insulin resistance. RESEARCH DESIGN AND METHODS: A
      prospective cohort study set in Australia in 2004-2006 followed up a cohort of
      647 adults who had participated in the Australian Schools Health and Fitness
      Survey in 1985 and who had undergone anthropometry and cardiorespiratory fitness
      assessment during the survey. Outcome measures were insulin resistance and
      obesity, defined as a homeostasis model assessment index above the 75th sex
      specific percentile and BMI >or=30 kg/m(2), respectively. RESULTS: Lower levels
      of child cardiorespiratory fitness were associated with increased odds of adult
      obesity (adjusted odds ratio [OR] per unit decrease 3.0 [95% CI 1.6-5.6]) and
      insulin resistance (1.7 [1.1-2.6]). A decline in fitness level between childhood
      and adulthood was associated with increased obesity (4.5 [2.6-7.7]) and insulin
      resistance (2.1 [1.5-2.9]) per unit decline. CONCLUSIONS: A decline in fitness
      from childhood to adulthood, and by inference a decline in physical activity, is
      associated with obesity and insulin resistance in adulthood. Programs aimed at
      maintaining high childhood physical activity levels into adulthood may have
      potential for reducing the burden of obesity and type 2 diabetes in adults.

PMID- 19106383
TI  - Percutaneous balloon mitral valvuloplasty: a review.

PMID- 19106382
TI  - Primary defects in beta-cell function further exacerbated by worsening of insulin
      resistance mark the development of impaired glucose tolerance in obese
      adolescents.
AB  - OBJECTIVE: Impaired glucose tolerance (IGT) is a pre-diabetic state of increasing
      prevalence among obese adolescents. The purpose of this study was to determine
      the natural history of progression from normal glucose tolerance (NGT) to IGT in
      obese adolescents. RESEARCH DESIGN AND METHODS: We determined the evolution of
      beta-cell function, insulin sensitivity (S(I)), and glucose tolerance in a
      multiethnic group of 60 obese adolescents over the course of approximately 30
      months. Each subject underwent three serial 3-h oral glucose tolerance tests.
      Dynamic, static, and total beta-cell responsivity (Phi(d), Phi(s), and Phi(tot),
      respectively) and S(i) were assessed by oral C-peptide and glucose minimal
      models. The disposition index (DI), which adjusts insulin secretion for S(i), was
      calculated. RESULTS: At baseline, all 60 subjects had NGT. Seventy-seven percent
      (46 subjects) maintained NGT over the three testing periods (nonprogressors),
      whereas 23% (14 subjects) developed IGT over time (progressors). At baseline,
      percent fat and BMI Z score were comparable between the groups. Fasting plasma
      glucose, 2-h glucose, glucose area under the curve at 180 min, and Phi(d) were
      significantly different between the two groups at baseline, whereas S(i) was
      comparable between the two groups. Over time, although S(i) remained unchanged in
      nonprogressors, it steadily worsened by approximately 45% (P > 0.04) in
      progressors. beta-Cell responsivity decreased by 20% in progressors, whereas it
      remained stable in nonprogressors. The DI showed a progressive decline in
      progressors compared with a modest improvement in nonprogressors (P = 0.02).
      CONCLUSIONS: Obese adolescents who progress to IGT may manifest primary defects
      in beta-cell function. In addition, progressive decline in S(i) further
      aggravates beta-cell function, contributing to the worsening of glucose
      intolerance.

PMID- 19106384
TI  - Images in cardiovascular medicine. Incomplete longitudinal ventricular septal
      fracture after blunt chest trauma.

PMID- 19106385
TI  - Letter by Joshi regarding article, "Optimal medical therapy with or without
      percutaneous coronary intervention to reduce ischemic burden: results from the
      clinical outcomes utilizing revascularization and aggressive drug evaluation
      (COURAGE) trial nuclear substudy".

PMID- 19106386
TI  - Letter by Tarantini et al regarding article, "Optimal medical therapy with or
      without percutaneous coronary intervention to reduce ischemic burden: results
      from the clinical outcomes utilizing revascularization and aggressive drug
      evaluation (COURAGE) trial nuclear substudy".

PMID- 19106388
TI  - Heart disease in Asia.

PMID- 19106389
TI  - Secular trends in the incidence of and risk factors for ischemic stroke and its
      subtypes in Japanese population.
AB  - BACKGROUND: The study of long-term trends in the incidence of and risk factors
      for ischemic stroke subtypes could offer insights into primary and secondary
      prevention. METHODS AND RESULTS: We established 3 cohorts of residents >/=40
      years of age in 1961, 1974, and 1988 in the Japanese community of Hisayama.
      Morphological examinations by autopsy or brain imaging were performed on most of
      the ischemic stroke cases developed in these cohorts. When 13-year follow-up data
      were compared, the age-adjusted incidence of ischemic stroke and lacunar
      infarction declined significantly from the first to the third cohort for both
      sexes, whereas the incidences of atherothrombotic and cardioembolic infarction
      did not change during this period. Hypertension was a powerful risk factor for
      the development of ischemic stroke, and improvement of hypertension control would
      have largely influenced this declining trend: The age- and sex-adjusted hazard
      ratio of hypertension decreased from 3.25 (95% CI 2.17 to 4.86) in the first
      cohort to 1.83 (1.29 to 2.58) in the third cohort. A rapid increase in the
      prevalence of metabolic disorders may have offset the impact of improvements in
      hypertension control and resulted in a slowdown of the decline in the incidence
      of ischemic stroke in the cohorts in the present study; however, hypertension
      still makes a large contribution to the development of ischemic stroke.
      CONCLUSIONS: These findings suggest that in the Japanese population, the
      incidence of ischemic stroke has declined significantly over the past 40 years,
      probably owing to better management of hypertension. There is a need for greater
      primary prevention efforts in the treatment of hypertension and metabolic
      disorders.

PMID- 19106390
TI  - Prevalence, awareness, treatment, and control of hypertension in China: data from
      the China National Nutrition and Health Survey 2002.
AB  - BACKGROUND: The present article aims to provide accurate estimates of the
      prevalence, awareness, treatment, and control of hypertension in adults in China.
      METHODS AND RESULTS: Data were obtained from sphygmomanometer measurements and an
      administered questionnaire from 141 892 Chinese adults >/=18 years of age who
      participated in the 2002 China National Nutrition and Health Survey. In 2002,
      approximately 153 million Chinese adults were hypertensive. The prevalence was
      higher among men than women (20% versus 17%; P<0.001) and was higher in
      successive age groups. Overall, the prevalence of hypertension was higher in
      urban compared with rural areas in men (23% versus 18%; P<0.01) and women (18%
      versus 16%; P<0.001). Of the 24% affected individuals who were aware of their
      condition, 78% were treated and 19% were adequately controlled. Despite evidence
      to suggest improved levels of treatment in individuals with hypertension over the
      past decade, compared with estimates from 1991, the ratio of controlled to
      treated hypertension has remained largely unchanged at 1:4. CONCLUSIONS: One in 6
      Chinese adults is hypertensive, but only one quarter are aware of their
      condition. Despite increased rates of blood pressure-lowering treatment, few have
      their hypertension effectively controlled. National hypertension programs must
      focus on improving awareness in the wider community, as well as treatment and
      control, to prevent many tens of thousands of cardiovascular-related deaths.

PMID- 19106391
TI  - Elevated heat shock protein 60 levels are associated with higher risk of coronary
      heart disease in Chinese.
AB  - BACKGROUND: Although heat shock protein 60 (Hsp60) is implicated in the
      pathogenesis of atherosclerosis, its role in coronary heart disease (CHD) is
      uncertain. This study explored the influence of circulating Hsp60 on CHD in a
      large case-control study, as well as the impact of acute myocardial infarction on
      Hsp60 levels in a prospective study. METHODS AND RESULTS: Plasma Hsp60 and anti
      Hsp60 antibody levels were determined by immunoassay. In the case-control study
      (1003 patients with CHD, 1003 matched control subjects), Hsp60 levels were higher
      in patients with CHD and were related to CHD (OR comparing extreme
      quartiles=4.14, P<0.0001). This association remained after adjustment for
      traditional risk factors (P for trend <0.0001). Individuals having high levels of
      Hsp60 (greater than the median of 160.24 ng/mL) and anti-Hsp60 antibody (greater
      than the median of 38.42 U/mL) were at a greater risk of CHD than those with low
      levels (OR 2.30, P<0.0001). Stronger additive effects (OR 14.04, P<0.0001) were
      apparent at higher Hsp60 and anti-Hsp60 antibody levels (>1000 ng/mL and greater
      than the median of 38.42 U/mL, respectively). The simultaneous presence of high
      Hsp60 and anti-Hsp60 antibody levels, current smoking, hypertension, and diabetes
      were cumulatively associated with CHD. Individuals who had any 4 or more of these
      5 factors had an OR of 38.61 for CHD (P<0.0001) compared with individuals who had
      none of these factors. For the prospective study, blood was drawn from 20
      patients immediately after admission for acute myocardial infarction and 2, 3,
      and 7 days thereafter. Hsp60 levels were significantly higher on the day of and
      the day after arrival than 7 days after an acute myocardial infarction (P=0.011
      and P=0.026, respectively). CONCLUSIONS: Elevated Hsp60 levels are associated
      with an increased risk for CHD, and Hsp60 and anti-Hsp60 antibody levels combine
      to increase this risk. In addition, acute myocardial infarction induces Hsp60
      release.

PMID- 19106392
TI  - Impact of kidney disease and blood pressure on the development of cardiovascular
      disease: an overview from the Japan Arteriosclerosis Longitudinal Study.
AB  - BACKGROUND: Kidney disease is associated with an increased risk of cardiovascular
      disease (CVD); however, there have been few well-designed prospective studies of
      this issue in Asian populations. Recent epidemiological studies have suggested
      that a lower blood pressure level may be associated with an increased risk of CVD
      in individuals with kidney dysfunction. METHODS AND RESULTS: Using data from 10
      community-based cohort studies in Japan, we conducted follow-up on a total of 30
      657 individuals 40 to 89 years of age without preexisting CVD or kidney failure
      and examined the relationship between reduced glomerular filtration rate (GFR)
      and the risk of CVD. During an average 7.4-year follow-up, 727 individuals
      experienced CVD. The age- and sex-adjusted incidence of CVD increased
      significantly in subjects with GFR of 60 to 89 mL . min(-1) . 1.73 m(-2) (4.3 per
      1000 person-years, P=0.002) and in those with a GFR <60 mL . min(-1) . 1.73 m(-2)
      (6.5, P<0.001) compared with those with a GFR >/=90 mL . min(-1) . 1.73 m(-2)
      (2.9). Even after adjustment for potential confounding factors, subjects with a
      GFR <60 mL . min(-1) . 1.73 m(-2) had a 57% (95% CI 14% to 115%) greater risk of
      CVD than those with a GFR >/=90 mL . min(-1) . 1.73 m(-2). The multivariate
      adjusted hazard ratios of CVD increased in a log-linear manner with elevations in
      blood pressure levels, regardless of GFR levels (all P for trend <0.01).
      CONCLUSIONS: Our findings suggest that a reduced GFR is a significant risk factor
      for CVD in the general Japanese population. Additionally, a log-linear
      association of blood pressure level with CVD risk was observed, without evidence
      of a J-curve association, regardless of GFR levels.

PMID- 19106394
TI  - Pharmacological intervention for prevention of left ventricular remodeling and
      improving prognosis in myocardial infarction.

PMID- 19106393
TI  - Cardiovascular disease and risk factors in Asia: a selected review.

PMID- 19106395
TI  - Stroke: Indian scenario.

PMID- 19106396
TI  - Changes in coronary heart disease risk among Japanese.

PMID- 19106397
TI  - Current status of percutaneous coronary intervention with drug-eluting stents in
      Asia.

PMID- 19106398
TI  - Overview of late outcome of medical and surgical treatment for Takayasu
      arteritis.

PMID- 19106399
TI  - Rheumatic heart disease in Asia.

PMID- 19106400
TI  - Takotsubo cardiomyopathy: a new form of acute, reversible heart failure.

PMID- 19106401
TI  - Long-term outcome of Kawasaki disease.

PMID- 19106402
TI  - Atherosclerotic Peripheral Vascular Disease Symposium II: executive summary.

PMID- 19106403
TI  - Atherosclerotic Peripheral Vascular Disease Symposium II: nomenclature for
      vascular diseases.

PMID- 19106404
TI  - Atherosclerotic Peripheral Vascular Disease Symposium II: screening for
      atherosclerotic vascular diseases: should nationwide programs be instituted?

PMID- 19106405
TI  - Atherosclerotic Peripheral Vascular Disease Symposium II: vascular magnetic
      resonance and computed tomographic imaging.

PMID- 19106406
TI  - Atherosclerotic Peripheral Vascular Disease Symposium II: stroke intervention:
      state of the art.

PMID- 19106407
TI  - Atherosclerotic Peripheral Vascular Disease Symposium II: controversies in
      carotid artery revascularization.

PMID- 19106408
TI  - Atherosclerotic Peripheral Vascular Disease Symposium II: controversies in
      abdominal aortic aneurysm repair.

PMID- 19106409
TI  - Atherosclerotic Peripheral Vascular Disease Symposium II: lower-extremity
      revascularization: state of the art.

PMID- 19106410
TI  - Atherosclerotic Peripheral Vascular Disease Symposium II: intervention for renal
      artery disease.

PMID- 19106411
TI  - Stimulation of Toll-like receptor 2 in human platelets induces a
      thromboinflammatory response through activation of phosphoinositide 3-kinase.
AB  - Cells of the innate immune system use Toll-like receptors (TLRs) to initiate the
      proinflammatory response to microbial infection. Recent studies have shown acute
      infections are associated with a transient increase in the risk of vascular
      thrombotic events. Although platelets play a central role in acute thrombosis and
      accumulating evidence demonstrates their role in inflammation and innate
      immunity, investigations into the expression and functionality of platelet TLRs
      have been limited. In the present study, we demonstrate that human platelets
      express TLR2, TLR1, and TLR6. Incubation of isolated platelets with Pam(3)CSK4, a
      synthetic TLR2/TLR1 agonist, directly induced platelet aggregation and adhesion
      to collagen. These functional responses were inhibited in TLR2-deficient mice
      and, in human platelets, by pretreatment with TLR2-blocking antibody. Stimulation
      of platelet TLR2 also increased P-selectin surface expression, activation of
      integrin alpha(IIb)beta(3), generation of reactive oxygen species, and, in human
      whole blood, formation of platelet-neutrophil heterotypic aggregates. TLR2
      stimulation also activated the phosphoinositide 3-kinase (PI3-K)/Akt signaling
      pathway in platelets, and inhibition of PI3-K significantly reduced Pam(3)CSK4
      induced platelet responses. In vivo challenge with live Porphyromonas gingivalis,
      a Gram-negative pathogenic bacterium that uses TLR2 for innate immune signaling,
      also induced significant formation of platelet-neutrophil aggregates in wild-type
      but not TLR2-deficient mice. Together, these data provide the first demonstration
      that human platelets express functional TLR2 capable of recognizing bacterial
      components and activating the platelet thrombotic and/or inflammatory pathways.
      This work substantiates the role of platelets in the immune and inflammatory
      response and suggests a mechanism by which bacteria could directly activate
      platelets.

PMID- 19106412
TI  - Oxidized low-density lipoproteins trigger endoplasmic reticulum stress in
      vascular cells: prevention by oxygen-regulated protein 150 expression.
AB  - Oxidized low-density lipoproteins (oxLDLs) trigger various biological responses
      potentially involved in atherogenesis. Disturbing endoplasmic reticulum (ER)
      function results in ER stress and unfolded protein response, which tends to
      restore ER homeostasis but switches to apoptosis when ER stress is prolonged. We
      aimed to investigate whether ER stress is induced by oxLDLs and can be prevented
      by the ER-associated chaperone ORP150 (150-kDa oxygen-regulated protein). oxLDLs
      and the lipid oxidation products 7-ketocholesterol and 4-hydroxynonenal induce ER
      stress in human endothelial cells (HMEC-1), characterized by the activation of ER
      stress sensors (phosphorylation of Ire1alpha and PERK, nuclear translocation of
      ATF6) and of their subsequent pathways (eukaryotic initiation factor 2alpha
      phosphorylation, expression of XBP1/spliced XBP1, CHOP, and KDEL chaperones
      GRP78, GRP94, ORP150). ER stress was inhibited by the antioxidant N
      acetylcysteine. In advanced atherosclerotic lesions, phospho-Ire1alpha, KDEL, and
      ORP150 staining were localized in lipid-rich areas with 4-hydroxynonenal adducts
      and CD68-positive macrophagic cells. By comparison, staining for 4
      hydroxynonenal, phospho-Ire1alpha, KDEL, and ORP were faint and more diffuse in
      intimal hyperplasia. ER stress takes part in the apoptotic effect of oxLDLs,
      through the Ire1alpha/c-Jun N-terminal kinase pathway, as assessed by the
      protective effect of specific small interfering RNAs and c-Jun N-terminal kinase
      inhibitor. Forced expression of the chaperone ORP150 reduced both oxLDL-induced
      ER stress and apoptosis. ER stress markers and ORP150 chaperone are expressed in
      areas containing oxLDLs in atherosclerotic lesions and are induced by oxLDLs and
      oxidized lipids in cultured cells. The forced expression of ORP150 highlights its
      new protective role against oxLDL-induced ER stress and subsequent apoptosis.

PMID- 19106413
TI  - G2A deficiency in mice promotes macrophage activation and atherosclerosis.
AB  - G2A is a stress-inducible G protein-coupled receptor that is expressed on several
      cell types within atherosclerotic lesions. We demonstrated previously that G2A
      deficiency in mice increased aortic monocyte recruitment and increased
      monocyte:endothelial interactions. To investigate the impact of G2A deficiency in
      macrophages, we isolated peritoneal macrophages from G2A(+/+)ApoE(-/-) and G2A(-/
      )ApoE(-/-) mice. G2A(-/-)ApoE(-/-) macrophages had significantly lower apoptosis
      than control macrophages. The prosurvival genes BCL-2, BCL-xL, and cFLIP were
      increased in G2A(-/-)ApoE(-/-) macrophages. Macrophages from G2A(-/-)ApoE(-/-)
      mice also had increased proinflammatory status that was indicative of a M1
      macrophage phenotype. This was indicated by significantly increased nuclear
      translocation of nuclear factor kappaB, as well as production of interleukin
      12p40, tumor necrosis factor alpha, and interleukin-6, and reduced expression of
      arginase-I. Moreover, G2A(-/-)ApoE(-/-) macrophages had reduced ability to engulf
      apoptotic cells in vitro. We examined atherosclerosis in mice fed a Western diet
      for 10 weeks and found that G2A deficiency increased lesion size in the aortic
      root by 50%. Plasma lipid levels were not changed in G2A(-/-)ApoE(-/-) mice.
      However, we found that absence of G2A increased the number of aortic macrophages
      and attenuated apoptosis in this cell type. Moreover, bone marrow transplantation
      studies indicated that deficiency of G2A in marrow-derived cells significantly
      contributed to atherosclerosis development. In the absence of G2A, increased
      macrophage activation and decreased apoptosis is associated with accumulation of
      macrophages in the aorta and increased atherosclerosis.

PMID- 19106414
TI  - Technology can improve public health education.

PMID- 19106415
TI  - Creative and tailored strategies needed to foster researcher-community
      partnerships.

PMID- 19106416
TI  - The anti-Chinese Cubic Air Ordinance.

PMID- 19106417
TI  - Food insecurity and risk of poor health among US-born children of immigrants.
AB  - OBJECTIVES: We investigated the risk of household food insecurity and reported
      fair or poor health among very young children who were US citizens and whose
      mothers were immigrants compared with those whose mothers had been born in the
      United States. METHODS: Data were obtained from 19,275 mothers (7216 of whom were
      immigrants) who were interviewed in hospital-based settings between 1998 and 2005
      as part of the Children's Sentinel Nutrition Assessment Program. We examined
      whether food insecurity mediated the association between immigrant status and
      child health in relation to length of stay in the United States. RESULTS: The
      risk of fair or poor health was higher among children of recent immigrants than
      among children of US-born mothers (odds ratio [OR] = 1.26; 95% confidence
      interval [CI] = 1.02, 1.55; P < .03). Immigrant households were at higher risk of
      food insecurity than were households with US-born mothers. Newly arrived
      immigrants were at the highest risk of food insecurity (OR = 2.45; 95% CI = 2.16,
      2.77; P < .001). Overall, household food insecurity increased the risk of fair or
      poor child health (OR = 1.74; 95% CI = 1.57, 1.93; P < .001) and mediated the
      association between immigrant status and poor child health. CONCLUSIONS: Children
      of immigrant mothers are at increased risk of fair or poor health and household
      food insecurity. Policy interventions addressing food insecurity in immigrant
      households may promote child health.

PMID- 19106418
TI  - Correlates of improvement in walking ability in older persons in the United
      States.
AB  - OBJECTIVES: We analyzed factors associated with improvement in walking ability
      among respondents to the nationally representative Health and Retirement Study.
      METHODS: We analyzed data from 6574 respondents aged 53 years or older who
      reported difficulty walking several blocks, 1 block, or across the room in 2000
      or 2002. We examined associations between improvement (versus no change,
      deterioration, or death) and baseline health status, chronic conditions, baseline
      walking difficulty, demographic characteristics, socioeconomic status, and
      behavioral risk factors. RESULTS: Among the 25% of the study population with
      baseline walking limitations, 29% experienced improved walking ability, 40%
      experienced no change in walking ability, and 31% experienced deteriorated
      walking ability or died. In a multivariate analysis, we found positive
      associations between walking improvement and more recent onset and more severe
      walking difficulty, being overweight, and engaging in vigorous physical activity.
      A history of diabetes, having any difficulty with activities of daily living, and
      being a current smoker were all negatively associated with improvement in walking
      ability. After we controlled for baseline health, improvement in walking ability
      was equally likely among racial and ethnic minorities and those with lower
      socioeconomic status. CONCLUSIONS: Interventions to reduce smoking and to
      increase physical activity may help improve walking ability in older Americans.

PMID- 19106419
TI  - The role of corporate credibility in legitimizing disease promotion.
AB  - OBJECTIVES: We explored what corporate "credibility" means to tobacco companies
      to determine why it matters to companies and what a lack of credibility means to
      them. METHODS: We collected documents from an online tobacco industry document
      archive and analyzed them with an interpretive approach. RESULTS: Tobacco
      companies conceptualized credibility not as being worthy of belief or confidence
      but as inspiring it. Thus, credibility was understood primarily as altering
      public perception of the industry. "Truth" was largely absent from tobacco
      industry conceptualizations of credibility, which were linked with
      "responsibility" and "reasonableness." However, industry research found that the
      public regarded credibility and responsibility differently, expecting these to
      entail truth telling, advertising reductions, less harmful products, apologies
      for deception, making amends, or exiting the tobacco business altogether.
      Overall, industry credibility-building projects failed repeatedly. CONCLUSIONS:
      Public health discourse increasingly attends to the roles of corporations in
      promoting disease. Industries such as tobacco and alcohol have been identified as
      profiting from harmful products. Yet corporations' ability to continue business
      as usual requires sustaining an implicit societal assent to their activities that
      depends on corporate credibility. For public health to address corporate disease
      promotion effectively, undermining corporate credibility may be strategically
      important.

PMID- 19106420
TI  - Perceptions of smoking-related risks and benefits as predictors of adolescent
      smoking initiation.
AB  - OBJECTIVES: The predictive value of perceptions of smoking-related risks and
      benefits with regard to adolescent smoking initiation has not been adequately
      established. We used prospective, longitudinal data to directly test whether
      smoking-related perceptions predict smoking initiation among adolescents.
      METHODS: We administered surveys assessing perceptions of smoking-related risks
      and benefits to 395 high school students, beginning at the start of their ninth
      grade year. We conducted follow-up assessments every 6 months until the end of
      10th grade, obtaining 4 waves of data. RESULTS: Adolescents who held the lowest
      perceptions of long-term smoking-related risks were 3.64 times more likely to
      start smoking than were adolescents who held the highest perceptions of risk.
      Adolescents who held the lowest perceptions of short-term smoking-related risks
      were 2.68 times more likely to initiate. Adolescents who held the highest
      perceptions of smoking-related benefits were 3.31 times more likely to initiate.
      CONCLUSIONS: Findings from this study provide one of the first sets of empirical
      evidence to show that smoking initiation is directly related to smoking-related
      perceptions of risks and benefits. Thus, efforts to reduce adolescent smoking
      should continue to communicate the health risks of smoking and counteract
      perceptions of benefits associated with smoking.

PMID- 19106421
TI  - Proximity of fast-food restaurants to schools and adolescent obesity.
AB  - OBJECTIVES: We examined the relationship between fast-food restaurants near
      schools and obesity among middle and high school students in California. METHODS:
      We used geocoded data (obtained from the 2002-2005 California Healthy Kids
      Survey) on over 500,000 youths and multivariate regression models to estimate
      associations between adolescent obesity and proximity of fast-food restaurants to
      schools. RESULTS: We found that students with fast-food restaurants near (within
      one half mile of) their schools (1) consumed fewer servings of fruits and
      vegetables, (2) consumed more servings of soda, and (3) were more likely to be
      overweight (odds ratio [OR] = 1.06; 95% confidence interval [CI] = 1.02, 1.10) or
      obese (OR = 1.07; 95% CI = 1.02, 1.12) than were youths whose schools were not
      near fast-food restaurants, after we controlled for student- and school-level
      characteristics. The result was unique to eating at fast-food restaurants
      (compared with other nearby establishments) and was not observed for another
      risky behavior (smoking). CONCLUSIONS: Exposure to poor-quality food environments
      has important effects on adolescent eating patterns and overweight. Policy
      interventions limiting the proximity of fast-food restaurants to schools could
      help reduce adolescent obesity.

PMID- 19106422
TI  - The influence of the physical environment and sociodemographic characteristics on
      children's mode of travel to and from school.
AB  - OBJECTIVES: We examined whether certain characteristics of the social and
      physical environment influence a child's mode of travel between home and school.
      METHODS: Students aged 11 to 13 years from 21 schools throughout London, Ontario,
      answered questions from a travel behavior survey. A geographic information system
      linked survey responses for 614 students who lived within 1 mile of school to
      data on social and physical characteristics of environments around the home and
      school. Logistic regression analysis was used to test the influence of
      environmental factors on mode of travel (motorized vs "active") to and from
      school. RESULTS: Over 62% of students walked or biked to school, and 72% from
      school to home. The likelihood of walking or biking to school was positively
      associated with shorter trips, male gender, higher land use mix, and presence of
      street trees. Active travel from school to home was also associated with lower
      residential densities and lower neighborhood incomes. CONCLUSIONS: Our findings
      demonstrate that active travel is associated with environmental characteristics
      and suggest that school planners should consider these factors when siting
      schools in order to promote increased physical activity among students.

PMID- 19106423
TI  - Motorcycle helmet laws in the United States from 1990 to 2005: politics and
      public health.
AB  - The passage of universal helmet legislation requiring motorcycle riders of all
      ages to wear helmets is a timely and controversial issue with far-reaching public
      health implications, especially as the number of motorcycle fatalities continues
      to rise. In 2008, only 20 states had a universal helmet policy, an effective
      safety measure for reducing motorcycle fatalities and serious injuries. We used
      state-specific longitudinal data for the continental United States from 1990
      through 2005 to determine which industry, political, economic, and demographic
      factors had a significant influence on the enactment of universal helmet
      policies. Our findings suggest that political climate and ideology are important
      predictors of helmet policies.

PMID- 19106424
TI  - Ethnic variations in prevalence of high-risk sexual behaviors among Asian and
      Pacific Islander adolescents in Hawaii.
AB  - OBJECTIVES: We examined ethnic variations in high-risk sexual behaviors among
      Asian and Pacific Islander (API) adolescents in comparison with White
      adolescents. METHODS: We obtained data from the 2003 Hawaii Youth Risk Behavior
      Survey on 4953 students in grades 9 through 12. We conducted chi(2) and logistic
      regression analyses on these data to examine the prevalence of high-risk sexual
      behaviors among Japanese, Filipino, Native Hawaiian, and White adolescents.
      RESULTS: We found significant ethnic variation in prevalence of high-risk sexual
      behaviors among API adolescents. Relative to White adolescents, Native Hawaiian
      adolescents were most likely to engage in lifetime sexual intercourse, recent
      sexual intercourse, and sexual initiation before age 13 years; Japanese
      adolescents were least likely to engage in these behaviors. Filipino adolescents
      were least likely to use substances before last sexual intercourse and condoms
      during last sexual intercourse. CONCLUSIONS: Our findings suggest divergent
      patterns of risk among API ethnic groups, underscoring the heterogeneity of API
      subgroups and emphasizing the need for health disparities research on
      disaggregated API ethnic groups. The findings of such research should be used to
      design ethnically relevant interventions aimed at mitigating the negative health
      consequences of high-risk sexual behaviors.

PMID- 19106425
TI  - Public awareness and use of direct-to-consumer genetic tests: results from 3
      state population-based surveys, 2006.
AB  - We conducted population-based surveys on direct-to-consumer nutrigenomic testing
      in Michigan, Oregon, and Utah as part of the 2006 Behavioral Risk Factor
      Surveillance System. Awareness of the tests was highest in Oregon (24.4%) and
      lowest in Michigan (7.6%). Predictors of awareness were more education, higher
      income, and increasing age, except among those 65 years or older. Less than 1%
      had used a health-related direct-to-consumer genetic test. Public health systems
      should increase consumer and provider education and continue surveillance on
      direct-to-consumer genetic tests.

PMID- 19106426
TI  - Racial/ethnic disparities in the identification of children with autism spectrum
      disorders.
AB  - OBJECTIVES: We sought to examine racial and ethnic disparities in the recognition
      of autism spectrum disorders (ASDs). METHODS: Within a multisite network, 2568
      children aged 8 years were identified as meeting surveillance criteria for ASD
      through abstraction of evaluation records from multiple sources. Through logistic
      regression with random effects for site, we estimated the association between
      race/ethnicity and documented ASD, adjusting for gender, IQ, birthweight, and
      maternal education. RESULTS: Fifty-eight percent of children had a documented
      autism spectrum disorder. In adjusted analyses, children who were Black (odds
      ratio [OR] = 0.79; 95% confidence interval [CI] = 0.64, 0.96), Hispanic (OR =
      0.76; CI = 0.56, 0.99), or of other race/ethnicity (OR = 0.65; CI = 0.43, 0.97)
      were less likely than were White children to have a documented ASD. This
      disparity persisted for Black children, regardless of IQ, and was concentrated
      for children of other ethnicities when IQ was lower than 70. CONCLUSIONS:
      Significant racial/ethnic disparities exist in the recognition of ASD. For some
      children in some racial/ethnic groups, the presence of intellectual disability
      may affect professionals' further assessment of developmental delay. Our findings
      suggest the need for continued professional education related to the
      heterogeneity of the presentation of ASD.

PMID- 19106427
TI  - Early childhood poverty and adult body mass index.
AB  - OBJECTIVES: We estimated associations between poverty in early, middle, and later
      childhood and adult body mass index to further elucidate the effects of
      socioeconomic status on health. METHODS: We conducted secondary analyses of data
      from men and women (N = 885) born between 1968 and 1975 who were tracked between
      their prenatal and birth years and adulthood in the nationally representative
      Panel Study of Income Dynamics. We used multivariate regression techniques and
      spline models to estimate the relationship between income in different stages of
      childhood and adult body mass index, overweight, and obesity. We controlled for
      other family characteristics, including income in other periods of childhood.
      RESULTS: Mean annual family income in the prenatal and birth years for children
      whose annual family incomes averaged less than $25,000 was significantly
      associated with increased adult body mass index, but mean annual family income
      between 1 and 5 years of age and between 6 and 15 years of age was not.
      CONCLUSIONS: Our results indicated that economic conditions in the earliest
      period of life (during the prenatal and birth years) may play an important role
      in eventual anthropometric measures.

PMID- 19106428
TI  - Update of the Drug Resistance Mutations in HIV-1.
AB  - The International AIDS Society-USA (IAS-USA) Drug Resistance Mutations Group
      reviews new data on HIV-1 drug resistance that have been published or presented
      at recent scientific meetings to maintain a current list of mutations associated
      with antiretroviral drug resistance.This December 2008 version of the IAS-USA
      drug resistance mutations figures updates those published in this journal in
      March/April 2008 (Johnson VA, Brun-Vezinet F, Clotet B, et al, Top HIV Med,
      2008;16:62-68). The compilation includes mutations that may contribute to a
      reduced virologic response to HIV-1 drugs. It should not be assumed that the list
      presented here is exhaustive. Drugs that have been approved by the US Food and
      Drug Administration (US FDA) as well as any drugs available in expanded access
      programs are included and listed in alphabetical order by drug class. The figures
      are designed for practitioners to use in identifying key mutations associated
      with viral resistance to antiretroviral drugs and in making therapeutic
      decisions.

PMID- 19106429
TI  - Drug-drug interactions with newer antiretroviral agents.
AB  - Knowledge of drug interactions among antiretroviral agents and other drugs used
      by HIV-infected patients is essential to maintaining safety and efficacy of drug
      treatment. Often, the clinical impact of drug-drug interactions cannot be
      predicted on the basis of pharmacokinetic interactions alone, highlighting the
      need for studies and analyses that provide exposure-response data. Drug
      interactions in HIV-infected patients can be complex and sometimes
      counterintuitive, and practitioners must increasingly rely on a concerted
      approach to gathering information on drug interactions that goes beyond studies
      showing exposure changes for coadministered drugs.

PMID- 19106430
TI  - Methicillin-resistant Staphylococcus aureus infections.
AB  - Community-acquired methicillin-resistant Staphylococcus aureus (MRSA) infection
      is epidemic in the community, differs from nosocomial MRSA in virulence,
      mechanisms, and antibiotic susceptibility, and exhibits diverse and often unique
      pathologic characteristics. The community-acquired MRSA USA 300 strains are
      transmitted largely by person-to-person contact and cause characteristic soft
      tissue abscesses and, less commonly, other sometimes unusual and serious
      infections including a necrotizing pneumonia, and other necrotic infections such
      as necrotizing fasciitis, pelvic thrombophlebitis, and septic phlebitis. This
      MRSA 300 family remains susceptible to drugs active against nosocomial MRSA (ie,
      vancomycin, linezolid, daptomycin) and is often susceptible to trimethoprim
      sulfamethoxazole, doxycycline, and clindamycin. Recent epidemiologic data
      indicate that nosocomial MRSA (eg, mainly USA 100) strains are also present in
      the community and that MRSA USA 300 strains are present in hospital settings,
      with both families found in intermediate frequency in health care-associated
      settings (eg, nursing homes, dialysis centers). More work is needed to identify
      effective barrier precautions to limit their spread.

PMID- 19106431
TI  - Improving engagement in HIV care: what can we do?
AB  - Engagement in HIV care needs to be improved. Important factors to be considered
      in attempts to improve engagement in care include the following: (1) initial
      linkage and subsequent retention are distinct processes; (2) engagement in care
      is vital for HIV treatment success at both the individual and population levels;
      (3) missed clinic visits can identify patients at high risk for poor health
      outcomes; (4) engagement in care is worse in groups bearing a disproportionate
      burden of the domestic HIV epidemic; and (5) ancillary services play a crucial
      role in improving linkage to and retention in care.

PMID- 19106432
TI  - Metals (Micro nutrients or toxicants) & Global Health.

PMID- 19106433
TI  - Nephrotoxicity of cadmium & lead.
AB  - Cadmium and lead are divalent cations with a propensity to settle in the proximal
      tubule of the nephron, leading to nephrotoxicity. The pathophysiological results,
      however, tend to diverge. Cadmium in sufficient cumulative dosage leads to the
      production of the Fanconi syndrome, a generalized proximal tubular reabsorptive
      defect thought to be related to inhibition of both ATP production and Na-K-ATPase
      activity. On the other hand, lead accumulation in the proximal tubule leads to
      hyperuricaemia and gout, presumably by inhibiting uric acid secretion, and
      diminished glomerular filteration rate (GFR). Fanconi syndrome is seen unusually
      only in children and experimental animals. Cadmium nephrotoxicity is heralded by
      increased excretion of beta2-microglobulin, retinol binding protein and alpha1
      microglobulin, indicative of decreased proximal tubule function. Beta2
      microglobulinuria is not found in lead nephropathy. In lead nephropathy
      albuminuria is absent or minimal whereas in cadmium nephropathy albuminuria is
      variable. From the standpoint of pathology, both entities are characterized by
      tubulointerstitial disease and fibrosis, but only early lead nephropathy is
      characterized by the presence of proximal tubule nuclear inclusion bodies, due to
      the combination of lead with a lead binding-protein.

PMID- 19106434
TI  - Carcinogenicity of hexavalent chromium.
AB  - Hexavalent chromium (Cr(VI)), a commonly used industrial metal, is a well known
      human lung carcinogen. Epidemiology and animal studies suggest that the
      particulate Cr(VI) compounds, specifically the water insoluble compounds, are the
      more potent carcinogens; however, the carcinogenic mechanism remains unknown.
      Here we summarize recent Cr(VI)-induced human tumour, in vivo, cell culture and
      in vitro studies and put the data into context with three major paradigms of
      carcinogenesis: multistage carcinogenesis, genomic instability, and epigenetic
      modifications. Based on these studies, we propose a mechanism for chromate
      carcinogenesis that is primarily driven by the genomic instability paradigm.

PMID- 19106435
TI  - Methylmercury neurotoxicity & antioxidant defenses.
AB  - Neurotoxicity induced by methylmercury (MeHg) increases the formation of reactive
      radicals and accelerates free radical reactions. This review summarizes recent
      findings in the MeHg-induced formation of free radicals and the role of oxidative
      stress in its neurotoxicity. Oxidative stress on CNS can produce damage by
      several interacting mechanisms, including mitochondrial damage with increase in
      intracellular free Ca(2+), activation and inhibition of enzymes, release of
      excitatory amino acids, metallothioneins expression, and microtubule disassembly.
      The nature of antioxidants is discussed and it is suggested that antioxidant
      enzymes and others antioxidants molecules may protect the central nervous system
      against neurotoxicity caused by MeHg.

PMID- 19106436
TI  - A comprehensive review of mercury provoked autism.
AB  - Emerging evidence supports the theory that some autism spectrum disorders (ASDs)
      may result from a combination of genetic/biochemical susceptibility, specifically
      a reduced ability to excrete mercury (Hg), and exposure to Hg at critical
      developmental periods. Elemental/inorganic Hg is released into the air/water
      where it becomes methylated and accumulates in animal tissues. The US population
      is primarily exposed to methyl-Hg by fish consumption. In addition, many
      pharmaceuticals have been, and some continue to be, a ubiquitous source of danger
      because they contain mercurials. Mercurials may be found in drugs for the eye,
      ear, nose, throat, and skin; in bleaching creams; as preservatives in cosmetics,
      tooth pastes, lens solutions, vaccines, allergy test and immunotherapy solutions;
      in antiseptics, disinfectants, and contraceptives; in fungicides and herbicides;
      in dental fillings and thermometers; and many other products. Hg has been found
      to cause immune, sensory, neurological, motor, and behavioural dysfunctions
      similar to traits defining/associated with ASDs, and that these similarities
      extend to neuroanatomy, neurotransmitters, and biochemistry. Furthermore, a
      review of molecular mechanisms indicates that Hg exposure can induce death,
      disorganization and/or damage to selected neurons in the brain similar to that
      seen in recent ASD brain pathology studies, and this alteration may likely
      produce the symptoms by which ASDs are diagnosed. Finally, a review of treatments
      suggests that ASD patients who undergo protocols to reduce Hg and/or its effects
      show significant clinical improvements in some cases. In conclusion, the
      overwhelming preponderance of the evidence favours acceptance that Hg exposure is
      capable of causing some ASDs.

PMID- 19106437
TI  - Nickel, its adverse health effects & oxidative stress.
AB  - Nickel-induced toxicity and carcinogenicity, with an emphasis on the generation
      and role of reactive oxygen species is reviewed. Nickel is a known haematotoxic,
      immunotoxic, neurotoxic, genotoxic, reproductive toxic, pulmonary toxic,
      nephrotoxic , hepatotoxic and carcinogenic agent. This article presents a
      selective review on nickel and effect of its acute, subchronic and chronic doses
      on certain metabolically active tissues in human as well as animals. Nickel
      exposure causes formation of free radicals in various tissues in both human and
      animals which lead to various modifications to DNA bases, enhanced lipid
      peroxidation, and altered calcium and sulphydryl homeostasis. The primary route
      for nickel toxicity is depletion of glutathione and bonding to sulphydryl groups
      of proteins. Nickel homeostasis, nickel-induced activation of signaling pathways
      and the protective role of enzymatic and non-enzymatic antioxidants against
      nickel toxicity and carcinogenicity are also discussed.

PMID- 19106438
TI  - Cardiovascular effects of lead exposure.
AB  - Several epidemiological and clinical studies have found a link between chronic
      lead exposure and elevated blood pressure. In addition, a few population studies
      have shown possible connection between lead exposure and other cardiovascular
      disorders including ischaemic coronary heart disease, cerebrovascular accidents,
      and peripheral vascular disease. The causal link between chronic lead exposure
      and hypertension (HTN) has been confirmed by several studies in experimental
      animals. In addition, the effects of lead on the heart and vascular function have
      been explored in a limited number of in vivo and in vitro studies. The in vivo,
      ex vivo and in vitro studies conducted in laboratory animal, cultured cells and
      isolated tissues have helped to elucidate many of the mechanisms by which lead
      exposure can cause HTN and cardiovascular disease. This review is intended to
      provide an overview of the epidemiology and the underlying mechanisms of lead
      associated HTN and cardiovascular disease.

PMID- 19106439
TI  - Chronic arsenic toxicity & human health.
AB  - Chronic arsenic toxicity (arsenicosis) due to drinking of arsenic contaminated
      ground water is a major environmental health hazard throughout the world
      including India. A lot of new information is emerging from extensive research on
      health effects of chronic arsenic toxicity (CAT) in humans during the last two
      decades. Available literature has been reviewed to highlight the problem
      including its malignancies. Pigmentation and keratosis are the specific skin
      lesions characteristics of CAT. CAT also produces various systemic manifestations
      over and above skin lesions, important ones being chronic lung disease like
      chronic bronchitis, chronic obstructive pulmonary disease and bronchiectasis,
      liver disease like non-cirrhotic portal fibrosis and other diseases like
      polyneuropathy, peripheral vascular disease, hypertension and ischeamic heart
      disease, diabetes mellitus, non-pitting oedema of feet/hands, weakness and
      anaemia. Cancer of skin, lung and urinary bladder are important cancers
      associated with chronic arsenic toxicity. Stoppage of drinking of arsenic
      contaminated water is the main stay in the management of arsenicosis as specific
      chelation therapy has limited value. Early skin cancer, detectable by regular
      active surveillance, is curable. In addition to dermatological features, CAT
      produces protean clinical manifestations. Treatment of arsenicosis is
      unsatisfactory and is mostly symtomatic.

PMID- 19106440
TI  - Copper & biological health.
AB  - Cu being a transition metal is ubiquitously engaged in biological systems to
      derive electrons through its participation in several enzymatic reactions. Upon
      bestowing the significance of Cu in biological systems, an elaborate mechanism is
      set forth by nature for maintaining Cu homeostasis. As a consequence, a wide
      variety of proteins viz., family of Cu bearing proteins, cuproenzymes, Cu
      transporters and Cu chaperone proteins have been manifested for enabling Cu to
      show its relevance in biological health. In addition, understanding the role of
      Cu in hepatic and neuronal functions and also in angiogenesis keeps progressing
      with the advent of novel molecular tools. The studies on genetic defects in Cu
      metabolism causing abnormalities are providing insights leading to the possible
      prognostic cues to alleviate the sufferings.

PMID- 19106441
TI  - Potential considerations & concerns in the risk characterization for the
      interaction profiles of metals.
AB  - The contaminants of concern for smelting and mining sites include arsenic (As),
      cadmium (Cd), lead (Pb) and zinc (Zn). Risk assessments for such sites need to
      consider whether toxicity values can be developed for this mixture, and if not,
      whether interactions among the individual components are significant and can be
      incorporated quantitatively into the assessment. No information is available for
      the risk characterization of the toxic interactions of AsCdPbZn mixtures. Studies
      of the AsCdPb and CdPbZn mixtures supported the assumption that a reasonable
      approximation to the toxicity of a mixture can be achieved by considering the
      binary submixtures. Data relevant to long-term simultaneous exposure to binary
      submixtures were not conclusive. For example, data from animal and human studies
      of Zn and Pb suggested that moderately elevated Zn intakes may slightly inhibit
      Pb absorption and haematological effects in children who have deficient or
      marginal Zn intakes, but were not adequate for adjusting absorption parameters in
      the Integrated Exposure Uptake Biokinetic (IEUBK) model for Pb. Thus the existing
      database calls for plausible approaches for risk characterization and
      considerations in the data usage for such characterization. This article is an
      attempt to identify such data gaps and the scientific considerations for such
      efforts.

PMID- 19106442
TI  - Manganese exposure, essentiality & toxicity.
AB  - Manganese (Mn) is an essential element present in all living organisms and is
      naturally present in rocks, soil, water, and food. Exposure to high oral,
      parenteral, or ambient air concentrations of Mn can result in elevations in Mn
      tissue levels and neurological effects. However, current understanding of the
      impact of Mn exposure on the nervous system leads to the hypothesis that there
      should be no adverse effects at low exposures, because Mn is an essential
      element; therefore, there should be some threshold for exposure above which
      adverse effects may occur and adverse effects may increase in frequency with
      higher exposures beyond that threshold. Data gaps regarding Mn neurotoxicity
      include what the clinical significance is of the neurobehavioural,
      neuropsychological, or neurological endpoints measured in many of the
      occupational studies that have evaluated cohorts exposed to relatively low levels
      of Mn. Specific early biomarkers of effect, such as subclinical neurobehavioural
      or neurological changes or magnetic resonance imaging (MRI) changes have not been
      established or validated for Mn, although some studies have attempted to
      correlate biomarkers with neurological effects. Experimental studies with rodents
      and monkeys provide valuable information about the absorption, bioavailability,
      and tissue distribution of various Mn compounds with different solubilities and
      oxidation states in different age groups. Studies have shown that rodents and
      primates maintain stable tissue manganese levels as a result of homeostatic
      mechanisms that tightly regulate absorption and excretion. In addition,
      physiologically based pharmacokinetic (PBPK) models are being developed to
      provide for the ability to conduct route-to-route extrapolations, evaluate nasal
      uptake to the CNS, and evaluate lifestage differences in Mn pharmacokinetics.
      Such models will facilitate more rigorous quantitative analysis of the available
      pharmacokinetic data for Mn and will be used to identify situations that may lead
      to increased brain accumulation related to altered Mn metabolism in different
      human populations, and develop quantitatively accurate predictions of increased
      Mn levels that may serve as a basis of dosimetry-based risk assessments. Such
      assessments will permit for the development of more scientifically refined and
      robust recommendations, guidelines, and regulations for Mn levels in the ambient
      environment and occupational settings.

PMID- 19106443
TI  - Heavy metal induced oxidative stress & its possible reversal by chelation
      therapy.
AB  - Exposure to heavy metals is a common phenomenon due to their environmental
      pervasiveness. Metal intoxication particularly neurotoxicity, genotoxicity, or
      carcinogenicity is widely known. This review summarizes our current understanding
      about the mechanism by which metalloids or heavy metals (particularly arsenic,
      lead, cadmium and mercury) induce their toxic effects. The unifying factor in
      determining toxicity and carcinogenicity for all these metals is the generation
      of reactive oxygen and nitrogen species. The toxic manifestations of these metals
      are caused primarily due to imbalance between pro-oxidant and antioxidant
      homeostasis which is termed as oxidative stress. Besides these metals have high
      affinity for thiol groups containing enzymes and proteins, which are responsible
      for normal cellular defense mechanism. Long term exposure to these metals could
      lead to apoptosis. Signaling components affected by metals include growth factor
      receptors, G-proteins, MAP kinases and transcription factors. Chelation therapy
      with chelating agents like calcium disodium ethylenediamine tetra acetic acid
      (CaNa(2)EDTA), British Anti Lewisite (BAL), sodium 2,3-dimercaptopropane 1
      sulfonate (DMPS), meso 2,3-dimercaptosuccinic acid (DMSA) etc., is considered to
      be the best known treatment against metal poisoning. Despite many years of
      research we are still far away from effective treatment against toxicity caused
      due to exposure to heavy metals/metalloids. The treatment with these chelating
      agents is compromised with number of serious side-effects. Studies show that
      supplementation of antioxidants along-with a chelating agent prove to be a better
      treatment regimen than monotherapy with chelating agents. This review attempts a
      comprehensive account of recent developments in the research on heavy metal
      poisoning particularly the role of oxidative stress/free radicals in the toxic
      manifestation, an update about the recent strategies for the treatment with
      chelating agents and a possible beneficial role of antioxidants supplementation
      to achieve the optimum effects. We have selected only arsenic, lead, mercury and
      cadmium for this article keeping in view current concerns and literature
      available.

PMID- 19106444
TI  - The interpretation of trace element analysis in body fluids.
AB  - The clinical interpretation of trace element analysis has lagged behind the
      technology available to measure the elements in body fluids. Reports can be
      difficult to interpret and requires knowledge of toxicokinetics, the dynamics of
      how the trace metals accumulate and pass through the body. Trace element analysis
      is best used for specific applications, such as establishing levels of exposure,
      biological exposure indices, biomonitoring of populations, and to confirm an
      association following a compatible diagnosis. It is not well suited for screening
      individual patients. Chelation treatment may follow inappropriate trace element
      determinations and may carry a risk of side effects, some life-threatening. Trace
      element analysis should be used sparingly and with full understanding of what the
      results are likely to mean. The physician should only order the test with a clear
      idea of why he or she is doing so and what he or she will do with the result.

PMID- 19106445
TI  - Iron transport & homeostasis mechanisms: their role in health & disease.
AB  - Iron is an essential trace metal required by all living organisms and is toxic in
      excess. Nature has evolved a delicately balanced network to monitor iron entry,
      transport it to sites of need, and serve as a unique storage and recycling
      system, in the absence of an excretory system, to remove excess iron. Due to the
      unique nature of iron metabolism, iron homeostasis is achieved by integrated
      specialized mechanisms that operate at the cellular and organism level. The use
      of positional cloning approaches by multiple researchers has led to the
      identification and characterization of various proteins and peptides that play a
      critical role in iron metabolism. These efforts have led to elucidation of the
      molecular mechanisms involved in the uptake of iron by the enterocytes,
      transportation across the membrane to circulation, and delivery to diverse
      tissues for use and storage and sensor system to co-ordinate and achieve
      homeostasis. Molecular understanding of these processes and the key regulatory
      molecules involved in maintaining homeostasis will provide novel insights into
      understanding human disorders associated with either iron deficiency or overload.

PMID- 19106446
TI  - Molecular toxicity of aluminium in relation to neurodegeneration.
AB  - Exposure to high levels of aluminium (Al) leads to neurofibrillary degeneration
      and that Al concentration is increased in degenerating neurons in Alzheimer's
      disease (AD). Nevertheless, the role of Al in AD remains controversial and there
      is little proof directly interlinking Al to AD. The major problem in
      understanding Al toxicity is the complex Al speciation chemistry in biological
      systems. A new dimension is provided to show that Al-maltolate treated aged
      rabbits can be used as a suitable animal model for understanding the pathology in
      AD. The intracisternal injection of Al-maltolate into aged New Zealand white
      rabbits results in pathology that mimics several of the neuropathological,
      biochemical and behavioural changes as observed in AD. The neurodegenerative
      effects include the formation of intraneuronal neurofilamentous aggregates that
      are tau positive, oxidative stress and apoptosis. The present review discusses
      the role of Al and use of Al-treated aged rabbit as a suitable animal model to
      understand AD pathogenesis.

PMID- 19106447
TI  - Cadmium & its adverse effects on human health.
AB  - Cadmium (Cd), a by-product of zinc production, is one of the most toxic elements
      to which man can be exposed at work or in the environment. Once absorbed, Cd is
      efficiently retained in the human body, in which it accumulates throughout life.
      Cd is primarily toxic to the kidney, especially to the proximal tubular cells,
      the main site of accumulation. Cd can also cause bone demineralization, either
      through direct bone damage or indirectly as a result of renal dysfunction. In the
      industry, excessive exposures to airborne Cd may impair lung function and
      increase the risk of lung cancer. All these effects have been described in
      populations with relatively high exposures to Cd in the industrial or in heavily
      polluted environments. Recent studies, however, suggest that the chronic low
      environmental exposure to Cd now prevailing in industrialized countries can
      adversely affect the kidneys and bones of the general population. These studies
      show consistent associations between various renal and bone biomarkers and the
      urinary excretion of Cd used to assess Cd body burden. The public health impact
      of these findings are still unknown. Further research is needed to ascertain that
      these associations are truly causal and not secondary to parallel changes in Cd
      metabolism and in the bone or kidney function occurring because of ageing or
      diseases unrelated to Cd exposure.

PMID- 19106448
TI  - Neuroendocrinology of social behavior.
AB  - Discovering the hormonal and neural mechanisms that promote affiliative social
      behavior is a high priority in behavioral neuroscience. Although studies with
      standard laboratory rodents have afforded many important insights, exciting
      advances are also occurring through comparative research with nonstandard species
      that vary in sociality or form socially monogamous pair bonds, work that is often
      informed by an explicitly evolutionary perspective. Research with prairie voles
      has examined the roles of sex steroid hormones, adrenal glucocorticoids, oxytocin
      family peptides, and dopamine in the formation of monogamous pairs.
      Corticosterone facilitates pairing by males but inhibits it in females,
      vasopressin (acting via the V1a receptor) and oxytocin facilitate pairing, and
      dopamine in the nucleus accumbens also facilitates pairing. Research with zebra
      finches is testing the limits of generality of these mechanisms, and has shown
      how sex steroid effects early in life along with social experience lead to an
      adult's sex preference in a pairing partner. Estrogen manipulations during the
      embryonic or nestling periods result in females that prefer to pair with other
      females. An all-female social environment can reinforce such effects, and can
      also produce males and females that will pair with either sex. Research with
      multiple species of estrildid finches is revealing the contributions of
      peptidergic and dopaminergic mechanisms to the evolution of species differences
      in whether animals are gregarious or territorial. Mechanisms for and responses to
      vasotocin (avian vasopressin) in the septal region of the brain are predicted by
      sociality in this group of birds.

PMID- 19106449
TI  - Evaluating the neurobiology of sexual reward.
AB  - There is much evidence that naturally occurring behaviors (e.g., the ingestion of
      food and water) and social behaviors (e.g., play, maternal behavior) can induce a
      reward state. This review includes definitions to distinguish between "reward"
      and "reinforcement," and a description of methods to assess reward and
      demonstrate that social interactions can indeed produce a positive affective (PA)
      state. Operant responses, partner preference, and sexual incentive motivation are
      all effective methods for evaluating approach behaviors under different
      conditions. The method most frequently used to evaluate a positive affective or
      reward state is conditioned place preference (CPP), which entails modification of
      an animal's initial preference after alternating exposure to a control stimulus
      in one chamber and a rewarding condition in the other. At the end of the training
      the animal shows a clear preference for the compartment associated with the
      rewarding stimulus. CPP demonstrates that it is possible to use different
      treatments and naturally occurring behaviors (e.g., water or food consumption,
      exercise) to induce a reward state. Sexual interactions and other social
      behaviors also produce a clear change of preference, indicating the induction of
      a reward or PA state. The reward state in males and females is mediated by
      opioids, and the medial preoptic area of the anterior hypothalamus is a crucial
      site for sexual reward.

PMID- 19106450
TI  - Olfactory regulation of the sexual behavior and reproductive physiology of the
      laboratory mouse: effects and neural mechanisms.
AB  - In many species, chemical compounds emitted by conspecifics exert profound
      effects on reproductive physiology and sexual behavior. This is particularly true
      in the mouse, where such cues advance and delay puberty, suppress and facilitate
      estrous cycles, and cause the early termination of pregnancy. They also
      facilitate sexual behavior and inform mate selection. The mouse has a rich and
      complex repertoire of social behaviors. The technologies of molecular genetics
      are well developed in the mouse. Gene expression can be experimentally
      manipulated in the mouse relatively easily and in a time- and tissue-specific
      manner. Thus, the mouse is an excellent model in which to investigate the
      genetic, neural, and hormonal bases by which chemical compounds released by other
      mice affect physiology and behavior. These chemical cues are detected and
      processed by the olfactory system and other specialized but less well
      characterized sensory organs. The sensory information reaches brain regions that
      regulate hormone levels as well as those that are involved in behavior and alters
      the function of these brain regions. The effects of these chemical compounds have
      important implications for the laboratory animal facility as well as for
      researchers. We begin with an overview of the basic structure and function of the
      olfactory system and of the connections among brain regions that receive
      olfactory stimuli. We discuss the effects of chemosensory cues on the behavior
      and physiology of the organism along with what is known about the neural and
      hormonal mechanisms underlying these effects. We also describe some of the
      implications for the laboratory animal facility.

PMID- 19106451
TI  - Communication of adult rats by ultrasonic vocalization: biological,
      sociobiological, and neuroscience approaches.
AB  - Rats have developed antipredator defensive adaptations to protect themselves from
      the large number of animals that prey on them. One such adaptation is the ability
      to communicate by ultrasonic vocalization, which decreases the likelihood of
      detection by a predator. Almost all rat vocalizations are inaudible to the human
      ear as well, so laboratory studies of ultrasonic vocalization require specialized
      electronic equipment. The most popular of these is the bat detector, which lowers
      ultrasonic frequency to a humanly audible frequency. Adult rats emit two types of
      ultrasonic calls: alarm (22 kHz) calls, in aversive and dangerous situations, and
      appetitive (50 kHz) calls, in appetitive or "friendly" (i.e., nonaggressive)
      behavioral situations. These two types of calls differ in all acoustic
      parameters, and their initiation depends on activity in different ascending
      tegmental pathways to the forebrain: 22 kHz calls require activity in the
      cholinergic system, and 50 kHz calls in the mesolimbic dopaminergic system. The
      release of acetylcholine in the diencephalon and forebrain is associated with the
      emission of 22 kHz vocalizations, and the release of dopamine in the nucleus
      accumbens with 50 kHz calls. Thus the two calls are reliable predictors of
      increased cholinergic or dopaminergic activity in the brain. The calls serve as
      indices of the rat's state, including its affective state, induced by activity of
      one or the other neurochemical system.

PMID- 19106452
TI  - The biopsychology of maternal behavior in nonhuman mammals.
AB  - The term "maternal behavior," when applied to nonhuman mammals, includes the
      behaviors exhibited in preparation for the arrival of newborn, in the care and
      protection of the newly arrived young, and in the weaning of those young, and
      represents a complex predictable pattern that is often regarded as a single,
      comprehensive, species-specific phenomenon. Although the delivering first-time
      mammalian mother is immediately and appropriately maternal, a "virgin" with no
      prior exposure to young does not show immediate and appropriate behavior toward
      foster young. Nevertheless, the virgin female, and indeed the male, possess the
      neural circuitry that underlies the pattern referred to as maternal behavior,
      despite not exhibiting the pattern under normal circumstances. At parturition, or
      after extensive exposure to young, what emerges appears to be a single
      stereotyped maternal behavior pattern. However, it is actually a smoothly
      coordinated constellation of simpler actions with proximate causes that, when
      sequenced properly, have the appearance of a motivated, purposive, adaptive
      pattern of caretaking. Over the past 50 years, much research has focused on
      finding the principal external and internal factors that convert the nonmaternal
      behavior patterns of the nonpregnant nullipara, the virgin, to the almost
      immediate and intense maternal behavior characteristic of the puerpera, the
      mother. This review is an attempt to summarize the many comprehensive, even
      encyclopedic, reviews of these factors, with an emphasis on brain mechanisms, and
      to highlight the gaps that remain in understanding the processes involved in the
      almost immediate onset of maternal caretaking behaviors observed in mammals at
      delivery. Where possible, the reader is directed to some of those excellent
      reviews.

PMID- 19106453
TI  - Optimization of laboratory conditions for the study of social behavior.
AB  - Social behavior--an action directed toward, or in response to, a member of the
      same species--is tightly regulated but also highly plastic. It is influenced by
      many internal (e.g., age, hormonal state, and experience) and external (e.g.,
      time of day, availability of food, encounters with conspecifics) factors. The
      study of social behavior in the laboratory can be challenging because many facets
      of social behavior are optimally expressed under specific circumstances. In
      addition, social behavior is particularly sensitive to environmental factors that
      are affected by routine animal husbandry. The goal of this article is to review
      for new investigators and for animal facility staff the major factors that can
      affect animals' social behavior in the laboratory in order to optimize conditions
      for the laboratory analysis of social behavior. The authors outline a basic
      theoretical foundation about the study of social behavior, including the concept
      of umwelt, an animal's subjective sensory world. They then briefly describe some
      of the most commonly studied social behaviors and a few examples of the basic
      methods to analyze these social behaviors. They discuss the potential effects of
      a facility's husbandry practices on social behavior and how to control these
      factors as well as possible, with suggestions of several new standard operating
      procedures toward this end. Although this paper focuses on rodents, the general
      principles apply to all species. The authors hope that the reader will consider
      all these factors when designing experiments or working in the animal facility.

PMID- 19106454
TI  - Behavioral studies and the IACUC: challenges and opportunities.

PMID- 19106455
TI  - Adequate veterinary care for animals in research: a comparison of guidelines from
      around the world.

PMID- 19106456
TI  - Proceedings of the Conference on Swine in Biomedical Research.
AB  - The Conference on Swine in Biomedical Research was held April 2-3, 2008, in San
      Diego, California. The goal of the conference was to bring together individuals
      who are using swine as models, creating new swine models, or studying human
      health and disease. This is the only conference that focuses exclusively on swine
      models and as such is the premier meeting for investigators who use or develop
      swine as models for biomedical research. The sessions focused on (1) swine models
      of human health and disease, (2) genomics, proteomics, and basic tools, (3)
      physiology and infectious disease, and (4) swine organ transplantation. In
      addition, a keynote speaker discussed the bioengineering of organ printing. This
      article presents a synopsis of the proceedings of this conference; abstracts of
      the presentations are available online (www.nsrrc.missouri.edu).

PMID- 19106457
TI  - Introduction: the neuroscience of social behavior.

PMID- 19106458
TI  - Adenylyl cyclase type 5 disruption prolongs longevity and protects the heart
      against stress.
AB  - Heart failure remains the leading cause of mortality in the USA, despite major
      advances in therapy over the past several decades, including angiotensin
      converting enzyme or angiotensin II inhibitors, vasodilators, calcium-channel
      blockers and beta-adrenergic receptor blockers. New therapeutic approaches are
      clearly required and the conceptual origin of these new techniques will be
      derived from agents that protect the heart against stress and prolong longevity.
      The combination of stress protection and longevity has been observed in a variety
      of organisms, from yeast to worms to mammals, and could be the basis for a novel
      approach to heart failure therapy. A mouse model has been developed with genetic
      disruption of adenylyl cyclase type 5, which lives one-third longer than the wild
      type and is protected from aging-induced, pressure overload-induced and
      catecholamine-induced stresses. Accordingly, inhibition of this molecule should
      be considered as a new therapeutic modality for heart failure.

PMID- 19106459
TI  - Impact of obstructive sleep apnea on the atrial electromechanical activation
      time.
AB  - BACKGROUND: Obstructive sleep apnea (OSA) is closely associated with atrial
      fibrillation, which is provoked by electrical and structural remodeling. However,
      the association between OSA and atrial remodeling has not been fully elucidated.
      METHODS AND RESULTS: Atrial electromechanical activation time (EMAT) was
      investigated using tissue Doppler imaging (TDI) in men with severe OSA (n=24) and
      control subjects (n=24). The EMAT was determined as the time interval from the
      initiation of P-wave deflection until the peak of local lateral left atrial (LA)
      TDI signal. The early diastolic velocity of the mitral annulus (E(a)) and the
      EMAT were significantly lower and longer in OSA cases than in controls (E(a):
      6.1+/-0.9 cm/s vs 7.3+/-1.5 cm/s, P=0.001; EMAT: 129.7+/-11.5 ms vs 118.5+/-12.3
      ms, P=0.002). Among OSA cases, the apnea - hypopnea index (AHI) was significantly
      correlated with EMAT (r=0.660, P<0.001), E(a) (r=-0.609, P=0.002), LA dimension
      (r=0.486, P=0.016), and early diastolic velocity of mitral flow (E)/E(a) ratio
      (r=0.418, P=0.042). In multivariate stepwise linear regression analysis, EMAT was
      independently associated with AHI (P=0.025) and E(a) (P=0.028) in OSA cases.
      CONCLUSION: EMAT measured by TDI could be a useful parameter for identifying
      atrial remodeling in patients with severe OSA.

PMID- 19106461
TI  - Hemoglobin, leukocytosis and clinical outcomes of ST-elevation myocardial
      infarction treated with primary angioplasty: ANIN Myocardial Infarction Registry.
AB  - BACKGROUND: Hemoglobin (Hb) levels may interact with inflammatory activation, but
      it is unknown whether the interaction has any impact on clinical outcomes in
      acute coronary syndromes. The aim of this study was to assess the relationship
      between admission Hb levels, leukocytosis and clinical outcomes of ST-elevation
      myocardial infarction (STEMI) treated with primary angioplasty. Methods and
      Results The study group comprised 1,904 (1,380 men) patients with STEMI treated
      with primary percutaneous coronary intervention, enrolled in a prospective
      registry. The primary endpoint of in-hospital death occurred in 90 (4.7%)
      patients. According to univariate analysis, extreme values of Hb (for 1(st) and
      5(th) vs mid quintiles respectively: hazard ratio (HR) =7.1, P<0.001 and HR =3.2,
      P=0.024) and leukocytosis above median (HR =2.09, P=0.001) significantly
      correlated with in-hospital death. After dividing patients into high and low
      white blood cell (WBC) count groups, a U-shaped relationship of Hb levels and
      mortality was observed for patients with higher leukocytosis (1(st) and 5(th) vs
      mid quintiles respectively: HR =8.1, P=0.001 and HR =4.4, P=0.022), whereas in
      patients with lower WBC count higher mortality was related solely to the lowest
      Hb quintile (HR =6.9, P=0.010 vs mid quintile). Conclusion Higher mortality
      associated with higher Hb levels in STEMI patients treated with primary
      angioplasty is limited to patients with increased leukocytosis.

PMID- 19106460
TI  - Clopidogrel resistance in Japanese patients scheduled for percutaneous coronary
      intervention.
AB  - BACKGROUND: Dual antiplatelet therapy with acetylsalicylic acid (ASA) and a
      P2Y(12) ADP-receptor blocker is standard for prevention of coronary stent
      thrombosis. Clopidogrel, a 2(nd)-generation P2Y(12) blocker, has recently become
      available in Japan and this study aimed to evaluate its antiplatelet effects in
      Japanese patients. METHODS AND RESULTS: Thirty Japanese patients scheduled for
      elective coronary stent implantation were enrolled. Under low-dose ASA therapy,
      300 mg clopidogrel was loaded on the 1(st) day and a daily 75-mg dose was
      administered on the following days. Assessed by optical aggregometer, rapid
      inhibition occurred at 4 h, when the inhibition of platelet aggregation rate
      (IPA) was 16.4+/-12.8% using 5 mumol/L ADP as the stimulus. The antiplatelet
      efficacy of clopidogrel was reasonably constant in each patient throughout the
      study period, although there was a broad inter-individual variation. At 48 h
      after clopidogrel loading, the ratios of responders (IPA > or =30%), hypo
      responders (10%< or =IPA<30%), and non-responders (IPA <10%) were 36%, 50%, and
      14%, respectively. CONCLUSIONS: The antiplatelet effectiveness of clopidogrel
      appeared individual-specific with wide inter-individual variation. The rate of
      clopidogrel non-responders was 14% among the examined Japanese patients.

PMID- 19106463
TI  - Root resorption and the OPG/RANKL/RANK system: a mini review.
AB  - Odontoclastic root resorption is a significant clinical issue in relation to
      orthodontic tooth movement, and resorption of the roots of primary teeth is an
      intriguing biological phenomenon. The functional coordination of the
      OPG/RANKL/RANK system seems to contribute not only to alveolar remodeling, but
      also to resorption during orthodontic tooth movement and physiological root
      resorption. Serum OPG and s-RANKL are related to regulation of bone homeostasis
      by the OPG/RANKL/RANK system, and determination of their concentrations might be
      useful for predicting the rate of bone remodeling during orthodontic tooth
      movement, the net effect between bone remodeling and root resorption, and the
      degree of root resorption. It is therefore rational to speculate that a study of
      the levels of OPG and s-RANKL in blood and GCF, in relation to the degree of root
      resorption during orthodontic tooth movement, using healthy experimental animals
      and a carefully planned and organized experimental design, may be able to answer
      this intriguing question.

PMID- 19106462
TI  - Optimal clinical pathway for the patient with type B acute aortic dissection.
AB  - BACKGROUND: The traditional medical treatment for type B acute aortic dissection
      (AAD) is widely accepted, but the optimal clinical pathway has not been
      confirmed. Methods and Results From admissions over the past 12 years, 210
      patients with uncomplicated type B AAD were divided into 2 groups: Conventional
      therapy group (CG) of 90 who were treated by 7 days of bed rest and intravenous
      antihypertensive agents and the Clinical pathway group (CPG) of 120 who were
      treated by early rehabilitation. In the CPG, patients were administered oral
      medication from the first day after onset and took a short walk from the third
      day after onset. The incidence of respiratory complications, and of delirium, was
      significantly decreased in the CPG. Early mortality was similar: 3.3% and 2.5%,
      respectively. The diameter of the aorta had not enlarged in either group 1 month
      later. Conclusions The clinical pathway of treatment for uncomplicated type B AAD
      was safer and better for preventing early complications and cost benefit.

PMID- 19106464
TI  - Steriods in the treatment of lichen planus: a review.
AB  - Steroids have been found to be effective in treating symptomatic oral lichen
      planus (OLP) by reducing pain and inflammation. In fact, systemic corticosteroids
      should be reserved for acute exacerbation, and multiple or widespread lesions.
      They may be indicated in patients whose condition is unresponsive to topical
      steroids. However, various potent topical steroids have been reported to be
      effective in the treatment of symptomatic OLP. They can be used as the first line
      drugs in the treatment of OLP with no serious side-effects. During the therapy,
      candidiasis was commonly found and in addition, bad taste, nausea, dry mouth,
      sore throat and swollen mouth may occur as minor side-effects from some topical
      steroids. Because OLP is a chronic disorder that requires long-term treatment,
      topical steroids are recommended for the treatment OLP because of minimal side
      effects and the cost benefit. This manuscript reviews the use of steroids,
      especially its topical application, in the treatment of OLP.

PMID- 19106465
TI  - 5-HT(1A) and 5-HT(1B) receptors in the ventrolateral striatum differentially
      modulate apomorphine-induced jaw movements in rats.
AB  - The ability of serotonin 5-HT(1A) and 5-HT(1B) receptors in the ventrolateral
      striatum to modulate dopamine receptor-mediated jaw movements was investigated in
      freely moving rats, using a magnet-sensing system combined with an intracerebral
      drug microinjection technique. Apomorphine (1 mg/kg i.v.) has been found to
      elicit repetitive jaw movements. Bilateral injections of the 5-HT(1A) receptor
      agonist 8-OH-DPAT (1 and 4 microg/0.2 microl in each side) into the ventrolateral
      striatum partially but significantly reduced apomorphine-induced repetitive jaw
      movements. The 5-HT(1A) receptor antagonist WAY-100635 (1 microg), which alone
      did not affect the effects of apomorphine, antagonized the inhibitory effects of
      8-OH-DPAT (4 microg). Bilateral injections of the 5-HT(1B) receptor agonist
      CP93129 (1 and 10 microg) also reduced apomorphine-induced repetitive jaw
      movements in a dose-dependent manner. However, the 5-HT(1B) receptor antagonist
      GR55562 (1 and 10 microg) did not antagonize the inhibitory effects of CP93129
      (10 microg). These results suggest that 5-HT(1A), but not 5-HT(1B), receptors in
      the ventrolateral striatum play a modulatory role in the production of dopamine
      receptor-mediated jaw movements.

PMID- 19106466
TI  - In vitro evaluation of the cytotoxicity of ProRoot MTA and MTA Angelus.
AB  - The purpose of the present in vitro study was to compare the cytotoxic effect of
      two commercially available brands of mineral trioxide cement (ProRoot MTA and MTA
      Angelus), modified zinc oxide-eugenol cement (SuperEBA) and resin-modified glass
      ionomer cement (Vitrebond) using rat pulp cells (RPC-C2A) and human lung
      fibroblasts (MRC-5). The cells were cultured in typical culture conditions and
      exposed to the tested materials by adaptation of insert wells. The cytotoxic
      effect was recorded at two observation periods (24 and 72 h) by using a
      colorimetric assay of tetrazolium reduction (XTT method) in reference to
      controls. Overall, the degree of cytotoxic effect in ascending order was ProRoot
      MTA - MTA Angelus < SuperEBA < Vitrebond. Both MTA materials tested exerted mild
      suppression of cellular mitochondrial activity and may be characterized as
      biologically inert materials.

PMID- 19106467
TI  - Repair potential of a laboratory-processed nano-hybrid resin composite.
AB  - The purpose of this study was to compare the 24-h composite-to-composite
      microtensile bond strength of Gradia Forte (GF) repaired with the same or a
      different material after different surface treatments. Different groups were set
      up, in which composite blocks of GF were subjected to the following treatments:
      Group 1, sandblasting with 50-microm aluminum oxide and 37% phosphoric acid
      etching (PA); Group 2, bur roughening and etching with 37% PA; Group 3, etching
      with 37% PA only. In all groups, a bonding resin was used as an intermediate
      agent prior to layering of the repair material (Gradia Direct (GD), Gradia (G),
      or GF). Bond strengths were then determined and analysed statistically. Scanning
      electron microscopy (SEM) evaluation of substrates and bonded interfaces was also
      performed. Surface treatment (P < 0.001) and repair materials (P < 0.001) were
      factors that significantly affected repair strength, whereas their interaction (P
      = 0.31) had no significant effect. Group 3 showed significantly superior repair
      strength to Groups 1 and 2, whereas Group 2 showed significantly weaker repair
      strength to Groups 1 and 3. Irrespective of surface treatment, GD and G gave
      similar results, which were better than those obtained using GF. The lowest
      probability of failure was found for GD and G in Group 3, whereas the highest was
      found for GF in Groups 1 and 2. Premature failures occurred mainly with G and GF.
      No pre-testing failures were found in the sandblasting/GD subgroup. Surface
      treated composites showed different textures under SEM, whereas composite-repair
      bonds showed comparable interfacial features.

PMID- 19106468
TI  - Effects of sodium bicarbonate on butyric acid-induced epithelial cell damage in
      vitro.
AB  - Butyric acid is detected in periodontal pockets and is thought to be involved in
      the initiation and progression of periodontal disease. We examined the effects of
      sodium bicarbonate on the butyric acid-induced epithelial cell damage. The human
      gingival carcinoma cell line Ca9-22 was cultured in medium that contained butyric
      acid with or without sodium bicarbonate. The viability of cells treated with
      sodium bicarbonate was significantly higher than that of cells treated with
      butyric acid alone. The effects of butyric acid on ICAM-1 expression were
      significantly improved by sodium bicarbonate. Within the limitations of this in
      vitro study, sodium bicarbonate was indicated to be a useful therapeutic agent to
      reduce the butyric acid-induced periodontal tissue damage.

PMID- 19106469
TI  - Lactoferrin suppress the adipogenic differentiation of MC3T3-G2/PA6 cells.
AB  - Lactoferrin accelerates the differentiation of osteogenic and chondrogenic
      lineage cells, whereas it inhibits the myogenic and adipogenic differentiation of
      pluripotent mesenchymal cells; however, the effect of lactoferrin on the
      differentiation of preadipocytes is unknown. In this study, we examined the
      effect of lactoferrin on adipogenic differentiation using a mouse preadipocyte
      cell line, MC3T3-G2/PA6. The cells were cultured in differentiation medium with
      or without lactoferrin to induce cellular differentiation. The cell lineage was
      then determined by Oil Red O staining, real-time PCR screening for the mRNA
      expression of phenotype-specific markers, and Western blot analysis. The number
      of Oil Red O-positive lipid droplets decreased following treatment with
      lactoferrin, as did the mRNA expression of C/EBPalpha, PPARgamma, aP2, and
      adiponectin. Furthermore, our Western blot data revealed a decrease in PPARgamma
      expression attributable to lactoferrin exposure. These results suggest that
      lactoferrin suppresses the adipogenic differentiation of MC3T3-G2/PA6 cells.

PMID- 19106470
TI  - The in vitro osteogenetic characteristics of primary osteoblastic cells from a
      rabbit calvarium.
AB  - Previously, we showed that recombinant human bone morphogenetic protein-2 (rhBMP
      2) increased bone augmentation beyond the skeletal envelope within a titanium cap
      in a rabbit calvarium; many cuboidal osteoblastic cells were observed
      histologically. These results suggested that the new osteoblastic cells might
      have differentiated and matured via stimulation by rhBMP-2. To date, however, no
      studies have reported the characteristics of osteoblastic cells derived from
      adult rabbit calvarium, after addition of rhBMP-2. To determine the effects of
      rhBMP-2 on osteoblastic cells, we observed morphological characteristics and
      alkaline phosphatase activity of osteoblastic cells from an adult rabbit
      calvarium. The expression of proteins in the BMP signaling pathway and
      extracellular matrix were analyzed, and mineralized nodule formation was
      assessed. The alkaline phosphatase activity increased significantly after rhBMP-2
      stimulation. The protein levels of phosphorylated-Smad1, Runx2, osteocalcin,
      osteopontin, and type I collagen were augmented by rhBMP-2 stimulation using
      Western blotting or ELISA; rhBMP-2 also stimulated mineralized nodule formation
      with alizarin red staining. The results suggest that primary osteoblastic cells
      derived from a rabbit calvarium have osteogenetic characteristics in vitro,
      underscoring the potential use of these cells as a model for studying bone
      formation. These cells may play an important role in in vivo bone augmentation in
      a rabbit experimental model.

PMID- 19106471
TI  - In vitro comparison of three different lengths of remaining gutta-percha for
      establishment of apical seal after post-space preparation.
AB  - The quality of apical seal with regard to the length of remaining gutta-percha
      following post-space preparation is still controversial. The purpose of this in
      vitro study was to compare three different lengths of remaining gutta-percha for
      apical seal after post-space preparation. A total of 126 single-rooted extracted
      maxillary human anterior teeth with intact apices, straight roots, and without
      resorption were used in this study. The root canals were prepared and filled with
      gutta-percha and AH26 sealer. The post-space preparation was accomplished. Ninety
      six teeth were randomly divided into three groups (4, 5 and 6 mm of gutta-percha
      was retained in group 1, 2 and 3, respectively).Thirty teeth were considered for
      the control groups in which 5 teeth served as positive and 5 teeth served as
      negative controls. The specimens were placed in India ink for 48 hours and then
      divided into two halves. The amount of leakage was observed and measured with a
      stereomicroscope at x 16 magnification and 0.1 mm accuracy. The results showed
      that there were significant differences among the three experimental groups (P <
      0.05). The best apical seal after post-space preparation was associated with the
      maximum length of remaining gutta-percha in the apical portion of the treated
      teeth.

PMID- 19106472
TI  - The effect of immersion disinfection procedures on dimensional stability of two
      elastomeric impression materials.
AB  - The aim of this study was to determine the effect of immersion disinfection
      procedures on the dimensional stability of two elastomeric impression materials.
      Impressions of a stainless steel die were made with polyether (PE) and with
      addition-polymerized silicone rubber (PVS). The test specimens underwent
      disinfection treatment by immersion in two commercially available solutions
      containing quaternary ammonium compounds (Sterigum Powder, SP) and glutaraldehyde
      plus an amino derivative (MD520, MD), respectively. The impressions were measured
      at 4 different time points: before any disinfection treatment (T0); after the
      first disinfection (T1); 6 hours after the first disinfection (T2); after the
      second disinfection, carried out 6 hours after the first one (T3). Impressions
      which were not disinfected served as controls. When both impression materials
      were disinfected with SP, significant differences were detected among all
      measurements (P < 0.0001), with the exception of T2 vs T3 (P > 0.05). On the
      other hand, when MD was used, significant differences were found when T0
      measurement was compared to T1, T2 and T3 measurements (P = 0.0043 for PE, and P
      = 0.0014 for PVS). The dimensional change of all material/disinfectant
      combinations was always <or=0.5%. Therefore, the effects of immersion
      disinfection on the dimension of elastomers in SP or MD are not clinically
      relevant.

PMID- 19106473
TI  - Simultaneous interrelationship between the oral health behavior and oral health
      status of mothers and their children.
AB  - The purpose of this study was to examine the simultaneous interrelationships of
      oral health behavior and oral health between mothers and their children using the
      linear structural relations (LISREL) program. The subjects comprised 117 pairs of
      mothers and their children aged between 8 and 11 years. Dental status was
      expressed as DMFT. The Oral Rating Index (ORI) for mothers and ORI for children
      (ORI-C) were used as measures of gingival health. Hiroshima University Dental
      Behavioral Inventory (HU-DBI) was used for the assessment of mothers' oral health
      behavior. HU-DBI had a direct positive relationship to ORI, a direct negative
      relationship to DFT, and a direct positive association with ORI-C. Toothbrushing
      had a direct negative relationship to ORI-C. The hypothesized model was found to
      be closely consistent with the data. These results indicate that the periodontal
      health status of mothers is directly related to the oral health status of their
      children, and that toothbrushing by children is directly related to their
      gingival health.

PMID- 19106474
TI  - Translation and validation of the Arabic version of the Geriatric Oral Health
      Assessment Index (GOHAI).
AB  - Our aim was to translate the original English version of the Geriatric Oral
      Health Assessment Index (GOHAI) into Arabic and assess its validity and
      reliability for use among people in North Jordan. After translation into Arabic
      and back-translation to check the translation quality, a total of 288
      participants completed the Arabic version of the GOHAI questionnaire. Individual
      GOHAI items were recoded and summed as originally recommended. The questionnaire
      sought information about socio-demographic characteristics and self-reported
      perception of general and oral health. Clinical examination included assessment
      of periodontal status, and number of decayed teeth, missing teeth, filled teeth
      and crowned teeth. Reliability, internal consistency, and concurrent, convergent
      and discriminant validity of GOHAI scores were examined. Mean GOHAI score was
      40.9 (SD = 10.6, range: 12 to 60). Cronbach's alpha for the GOHAI score was 0.88,
      indicating a high degree of internal consistency and homogeneity between the
      GOHAI items. The test-retest correlation coefficient for add-GOHAI scores was
      0.72, indicating good stability. Add-GOHAI scores increased with poorer perceived
      general and oral health. Convergent validity, construct validity and discriminant
      validity of the GOHAI were demonstrated. The Arabic translation of the GOHAI
      demonstrated acceptable validity and reliability when used for people in North
      Jordan. It could therefore be used as a valuable instrument for measuring oral
      health-related quality of life for people in this region.

PMID- 19106475
TI  - Reduction of micronuclei in oral lichen planus supplemented with beta-carotene.
AB  - An elevated frequency of micronucleated exfoliated cells (MEC) in atrophic and
      erosive oral lichen planus (OLP) has been reported. To evaluate the effects of
      supplemental beta-carotene (BC) on MEC frequency in OLP lesions, we performed an
      open trial in 20 patients with atrophic and/or erosive OLP. Each patient received
      15 mg of BC four times daily for 3 months. The frequency of MEC in both lesions
      and adjacent normal mucosa in each patient was evaluated and compared before and
      after supplementation. Serum levels of BC and retinol were also determined. After
      BC supplementation, all patients had higher levels of serum BC and retinol. The
      MEC frequency in OLP lesions was significantly reduced (P < 0.01). No significant
      changes were seen in the MEC frequency in adjacent normal mucosa. BC
      supplementation thus significantly reduces MEC frequency in atrophic and erosive
      OLP.

PMID- 19106476
TI  - Antibacterial effects of five different root canal sealing materials.
AB  - The aim of this in vitro study was to assess the antibacterial effects of gray
      and white mineral trioxide aggregate (GMTA and WMTA), calcium hydroxide (CH),
      Portland cement (PC) and a new endodontic cement (NEC) on various species of
      microorganisms, using agar diffusion test. A base layer of Petri plates was made
      using Muller-Hinton agar. Five cavities were made in agar and filled with fresh
      mixed materials after 24 h. Pseudomonas aeruginosa, Enterococcus faecalis,
      Staphylococcus aureus, Escherichia coli and a mixture of these bacteria were
      seeded by pour plate. The plates were preincubated for 2 h at room temperature
      followed by incubation at 37 degrees C. The inhibition zone diameters were
      measured at 24, 48 and 72 h. The highest mean diameters of growth inhibition
      zones were observed around NEC and CH. According to one-way ANOVA, there was a
      significant difference among test groups (P < 0.001), while post-hoc test
      revealed no significant difference between the mean zone diameters of NEC and CH,
      and also between MTAs and PC. However, there was a significant difference between
      CH and NEC in comparison with MTAs and PC groups (P < 0.001). It appears that NEC
      may act as a potent antibacterial agent similar to CH.

PMID- 19106477
TI  - Comparison between a profilometer and a measuring microscope for measurement of
      enamel erosion.
AB  - The aim of this study was to measure the difference in the erosion depth of
      enamel measured by profilometry (PM) and a measuring microscope (MM). Sixty
      enamel specimens were divided into ten groups. Each specimen group was exposed to
      50 ml of a carbonated drink with pH 2.38 or orange juice with pH 3.67 for 15, 30,
      60, 120, and 180 minutes. Depths of eroded areas were measured with a
      profilometer and a measuring microscope. Data of average enamel loss were
      measured by PM and MM for all erosion times and were scatter plotted on a graph
      with regression fit. Correlations between the enamel loss measured by PM and MM
      were analyzed with a paired sample t-test to compare the discriminatory abilities
      of the two methods of analysis for all erosion times. The regression fit in all
      study cases showed a high linear relationship (R(2) = 0.90) between measurements
      by PM and MM, but in cases where the erosion depth was lower than the depth of
      focus (DOF) of the MM objective lens, there were weak correlation coefficients (
      0.007 - 0.303) for comparison between the two measurement methods.

PMID- 19106479
TI  - Cervical external root resorption: 3-year follow-up of a case.
AB  - Cervical external root resorption can be present in natural teeth, involving one
      or more teeth in the same patient. The incidence of these lesions appears random
      and the etiology remains unclear. Cervical external root resorption has been
      considered a difficult clinical situation, and its diagnosis and treatment of the
      defect challenging. The present report describes a case of multiple external
      cervical resorption lesions involving four teeth, including the history, and the
      clinical and radiographic findings. The treatment included surgical intervention
      and restoration of the defect without sacrificing the pulp. A 3-year re
      evaluation of the case confirmed a stable, uneventful clinical recovery.

PMID- 19106478
TI  - Changes in elastic modulus of adhesive and adhesive-infiltrated dentin during
      storage in water.
AB  - The purpose of this study was to determine the elastic modulus of components at
      the resin-dentin interface with the use of an ultrasound device. Dentin slabs
      were obtained from freshly extracted bovine incisors shaped into a rectangular
      form. After demineralization, the dentin specimens were immersed in adhesives and
      polymerized. Adhesives were also polymerized and trimmed into the same shape as
      the dentin slabs. The specimens were then immersed in distilled water at 37
      degrees C for up to one year. The ultrasound equipment employed in this study was
      a Pulser-Receiver, transducers and an oscilloscope. By measuring the longitudinal
      and shear wave sound velocities, the elastic modulus was determined. When the
      elastic modulus of adhesive resin-infiltrated demineralized dentin was compared
      with that of adhesives, slightly but significantly lower values were found for
      adhesives used in a self-etching primer system. On the other hand, a higher
      elastic modulus was observed for resin-infiltrated dentin than for an adhesive
      used in an etch and rinse system. The elastic modulus of the resin-infiltrated
      dentin prepared with the etch and rinse system was affected by long-term storage
      in distilled water.

PMID- 19106480
TI  - General anesthesia for a patient with deletion 6q syndrome in addition to
      laryngomalacia undergoing dental treatment.
AB  - Chromosome 6 deletions are very rare (1,2), and deletion 6q syndrome is
      clinically characterized by mental and/or neuromotor retardation and microcephaly
      (3). Other alterations frequently observed are decreased biparietal diameter,
      hypertelorism, hypotelorism, absent eyebrows, prominent eyes with ptosis,
      receding chin, dysmorphic ears, large extremities, prominent nasal bridge, long
      philtrum, epicthus, strabismus, and micrognathia (3-5). Laryngomalacia is the
      most common congenital laryngeal anomaly and the most frequent cause of stridor
      in infants (6-11). We report the case of a 14-year-old male patient with both
      deletion 6q syndrome and laryngomalacia, who we treated for multiple dental
      caries. He had a medical history of tracheotomy at age 11 years for
      laryngomalacia, and has suffered from epileptic attacks and aspiration pneumonia
      over the last 2 and 6 years, respectively. Since he was mentally retarded and in
      a poor respiratory state, dental treatment under general anesthesia was scheduled
      in our hospital. General anesthesia was induced and maintained using 30% nitrous
      oxide and 1-3% sevoflurane in oxygen through the tracheotomy tube. Pre- and
      intraoperative endotracheal suction improved the condition of both lungs markedly
      and the procedures were uneventful and completed in 2 h and 58 min.

PMID- 19106481
TI  - Dietary calcium and 1,25-dihydroxyvitamin D3 regulate transcription of calcium
      transporter genes in calbindin-D9k knockout mice.
AB  - The effect(s) of oral calcium and vitamin D(3) were examined on the expression of
      duodenal and renal active calcium transport genes, i.e., calbindin-D9k (CaBP-9k)
      and calbindin-D28k (CaBP-28k), transient receptor potential cation channels
      (TRPV5 and TRPV6), Na(+)/Ca(2+) exchanger 1 (NCX1) and plasma membrane calcium
      ATPase 1b (PMCA1b), in CaBP-9k KO mice. Wild-type (WT) and KO mice were provided
      with calcium and vitamin D(3)-deficient diets for 10 weeks. The deficient diet
      significantly decreased body weights compared with the normal diet groups. The
      serum calcium concentration of the WT mice was decreased by the deficient diet
      but was unchanged in the KO mice. The deficient diet significantly increased
      duodenal transcription of CaBP-9k and TRPV6 in the WT mice, but no alteration was
      observed in the KO mice. In the kidney, the deficient diet significantly
      increased renal transcripts of CaBP-9k, TRPV6, PMCA1b, CaBP-28k and TRPV5 in the
      WT mice but did not alter calcium-relating genes in the KO mice. Two potential
      mediators of calcium-processing genes, vitamin D receptor (VDR) and parathyroid
      hormone receptor (PTHR), have been suggested to be useful for elucidating these
      differential regulations in the calcium-related genes of the KO mice. Expression
      of VDR was not significantly affected by diet or the KO mutation. Renal PTHR mRNA
      levels were reduced by the diet, and reduced expression was also seen in the KO
      mice given the normal diet. Taken together, these results suggest that the active
      calcium transporting genes in KO mice may have resistance to the deficiency diet
      of calcium and vitamin D(3).

PMID- 19106482
TI  - Importance of the porcine ADAM3 disintegrin domain in sperm-egg interaction.
AB  - In the mouse, ADAM3, a well-characterized testis-specific protein of the A
      disintegrin and metalloprotease (ADAM) family, has a crucial role in
      fertilization by mediating sperm binding to the egg zona pellucida. However,
      little is known about ADAM3 in other species, such as domestic pigs. We have
      identified porcine ADAM3 and analyzed the protein. RT-PCR and trypsinization of
      sperm surface proteins revealed that porcine ADAM3 is expressed at high levels in
      the testis and on the sperm surface. Furthermore, an IVF inhibition assay with a
      recombinant porcine ADAM3 disintegrin domain showed that treatment of the
      disintegrin domain effectively prevented pig sperm-egg interactions. In the
      present study, we demonstrated the presence of ADAM3a and ADAM3b molecules in the
      pig and examined their roles in fertilization.

PMID- 19106483
TI  - Acute changes in circulating concentrations of progesterone and nitric oxide and
      partial pressure of oxygen during prostaglandin F2alpha-induced luteolysis in
      cattle.
AB  - To examine whether oxygen (O(2)) and nitric oxide (NO) are temporally associated
      with the acute changes in luteal function during luteolysis, we determined the
      real-time changes in the circulating concentrations of progesterone (P4) and
      nitrite/nitrate (the stable metabolites of NO) and the partial pressure of oxygen
      (pO(2)) during prostaglandin F(2alpha) (PGF(2alpha))-induced luteolysis in
      cattle. Catheters for frequent blood sample collection were inserted into the
      ovarian vein (OV), jugular vein (JV) and aorta abdominalis (AA) in 12 cows on Day
      9 of the oestrous cycle (oestrus=Day 0). On Day 10, the cows were randomly
      divided into two groups and treated with a luteolytic dose of a PGF(2alpha)
      analogue or saline solution (control). Blood samples were collected at -2, -1, 0,
      0.25, 0.5, 0.75, 1 and 2 h and then at 2-h intervals until 12 h after treatment
      (0 h). Injection of a PGF(2alpha) induced a significant decrease in the
      concentrations of P4 in OV plasma within 2 h. The decrease in P4 concentrations
      was preceded by an increase in the NO concentrations in the blood collected from
      OV, JV and AA. Basal pO(2) was significantly higher in OV blood than in JV blood
      (P<0.05). PGF(2alpha) injection increased pO(2) in OV blood between 0.5 and 2 h.
      These results demonstrate that PGF(2alpha) induced an acute increase in pO(2) and
      NO in the ovarian circulation and suggest that O(2) and NO are involved in the
      early events of CL regression, including inhibition of P4 secretion and output,
      in cattle.

PMID- 19106484
TI  - Production of cloned pigs by nuclear transfer of preadipocytes following cell
      cycle synchronization by differentiation induction.
AB  - Four methods of cell cycle synchronization of porcine preadipocytes for use as
      nuclear donors in somatic cell cloning were compared: serum starvation,
      differentiation induction, contact inhibition and roscovitine treatment. After
      three days of differentiation induction, the percentage of nuclear donor cells
      synchronized at the G0/G1 phase reached a peak value of 91.8%, which was
      significantly higher (P<0.05) than the percentage attained by serum starvation
      (84.9-89.8%), contact inhibition (78.3-83.7%) or roscovitine treatment (67.8
      80.3%). Cell cycle synchronization by serum starvation, contact inhibition and
      roscovitine treatment all increased the percentage of apoptotic cells, while no
      increase was observed when the donor-cell cycle was synchronized by
      differentiation induction (Annexin V-positive: 15.7% to 19.3% vs. 7.7%, P<0.05;
      TUNEL-positive: 12.8% to 14.0% vs. 8.3%, P<0.05). Additionally, comparison of the
      in vitro development of nuclear transfer (NT) embryos formed from the nuclei of
      differentiation-induced or serum-starved preadipocytes revealed that, in both
      cases, a high proportion of embryos developed to the blastocyst stage (39.0 and
      33.7%, respectively). In this study, NT embryos reconstructed with preadipocytes
      synchronized by differentiation induction were transferred to four recipient
      pigs, three of which gave birth to a total of 17 piglets (4.2%, 17/403). These
      results demonstrate that donor-cell cycle synchronization by differentiation
      induction enables effective production of cloned pigs. The findings also indicate
      that differentiation induction of multipotent cells is an excellent method of
      cell cycle synchronization that permits highly efficient synchronization of cells
      at the G0/G1 phase.

PMID- 19106485
TI  - Fetal age estimation of Hokkaido sika deer (Cervus nippon yesoensis) using
      ultrasonography during early pregnancy.
AB  - In sika deer, the normal method of estimating fetal age, based on fetal weight,
      is not applicable during the early pregnancy period. The objective of the present
      study was to describe the growth and development of sika deer fetuses and to
      establish a method for fetal age estimation during early pregnancy using
      ultrasonography. Five captive female Hokkaido sika deer (Cervus nippon yesoensis)
      were observed for estrus and mated (day 0) with an intact male. At two- or three
      day intervals, fetuses were observed by rectal ultrasonographic scans until 59-61
      days of gestation. The straight crown-rump length (SCRL), curved crown-rump
      length (CCRL), head length (HL), trunk depth (TD) and heart rate (HR) of the
      fetuses were measured. Linear regression equations were computed for each
      measurement together with fetal age. Analyses were conducted after transformation
      to a natural logarithm for SCRL and CCRL. All equations were significant
      (P<0.001), with SCRL becoming measurable earlier (day 20) than the others and
      yielding the best correlation (Days= -2.08+14.15 LnX: X=SCRL, Ln=natural
      logarithm). Therefore, we concluded that a precise estimation of fetal age in
      early gestation is best performed using SCRL measurements.

PMID- 19106486
TI  - Kinetics of nuclear status and kinase activities during in vitro maturation of
      canine oocytes.
AB  - In contrast to those of other mammals, canine oocytes are ovulated at the
      germinal vesicle (GV) stage and then progress to the metaphase II (MII) stage in
      the oviduct. In other species, oocytes at the MII are widely used for in vitro
      fertilization or as recipients in somatic cell nuclear transfer. Many researchers
      have tried to improve the in vitro maturation (IVM) of canine oocytes. However,
      the proportion of MII oocytes remains low, resulting in poor efficiency of
      embryogenesis in vitro. This leads us to the possibility that the in vitro
      cytoplasmic maturation of canine oocytes is insufficient. Furthermore, the
      optimal culture period for IVM of canine oocytes is controversial, and
      physiological evaluation is required to improve canine IVM. We show here the time
      dependent changes in mitogen-activated protein kinase (MAPK) and p34(cdc2) kinase
      activities in canine oocytes during IVM, since it is well known that both MAPK
      and p34(cdc2) kinase are activated following meiotic progression and show high
      activities in the MII stage in other species. Immediately after collection from
      ovaries, most oocytes were arrested at the GV stage, which was maintained until
      24 h of culture. At 48 h of culture, more than half of the oocytes had progressed
      beyond the MI stage. A higher proportion of MII oocytes were observed with 72 h
      of culture compared with other culture periods. MAPK activity was found to
      increase in a time-dependent manner and reached a plateau at 72 h of culture. The
      level of p34(cdc2) kinase activity also increased in a time-dependent manner,
      with its maximal level observed after 72 h of culture. Activity was decreased
      with 96 h of culture, although there was no significant difference in the
      proportion of MII oocytes between 72 and 96 h. Our data thus show that the
      optimal culture period for IVM of canine oocytes is 72 h because both MAPK and
      p34(cdc2) kinase showed high activities at that time.

PMID- 19106487
TI  - Production of transgenic pigs harboring the human erythropoietin (hEPO) gene
      using somatic cell nuclear transfer.
AB  - The production of transgenic pigs using somatic cell nuclear transfer (scNT) has
      been widely described, but a technique for removing nontransfected donor cells
      and for creating different founder animals has not yet been fully elucidated. In
      this study, four different expression vectors (pBC1hEPO, pMARBC1hEPO,
      pBC1hEPOwpre and pMARBC1hEPOwpre) were compared to determine the highest
      transgene expression, ideal conditions of enrichment of recombinant cells in
      vitro and efficiency of transgenesis following transfection into HC11 mammary
      epithelial cells. The highest protein expression in HC11 cells was obtained from
      the pMARBC1hEPOwpre expression vector. Next, we evaluated the efficiency of
      transgenic pig production by using geneticin (G418) selection alone or by using
      real-time PCR selection following G418 selection. Ideal enrichment of recombinant
      cells was obtained by a combination of real-time PCR and G418 selection; embryos
      reconstructed using donor cells selected by a combination of real-time PCR and
      G418 selection gave rise to nine piglets, all of which were transgenic. Among
      them, three founder transgenic pigs were established. Exogenous DNA fragments
      were shown to be integrated into chromosomes 1q2.4, 1p2.3 and 6q2.4,
      respectively, in these three pigs. However, the transgenic rate using G418
      selection alone was only 33% (two of six pigs) and showed a very low efficacy
      compared with that of the combination of real-time PCR and G418 selection. Our
      results provide a valuable experimental model for applying and evaluating
      transgenic technology in pigs.

PMID- 19106488
TI  - Leptin Receptor (Ob-R) expression in the ovary and uterus of the wild japanese
      black bear (Ursus thibetanus japonicus).
AB  - To verify target organ(s) of leptin in the reproductive system of the Japanese
      black bear, we examined the expression of leptin receptor (Ob-R) protein in
      ovaries and uteri collected from July to December 2006 by immunohistochemical
      techniques. Eleven of 22 female Japanese black bears examined had corpora lutea
      (CLs) in their ovaries and were thought to have undergone or to have terminated
      delayed implantation in the early pregnancy stage. The CLs were classified into 3
      types based on morphological features. The maximum diameters of Type 1 CLs ranged
      3 to 7 mm, and the luteal cells contained numerous vacuoles in the cytoplasm,
      which suggests that this type of CL was functional. The maximum diameters of Type
      2 CLs were approximately 7 mm, and the luteal cells contained fewer vacuoles in
      the cytoplasm, which suggests that this type of CL was in the early stage of
      regression. Finally, the maximum diameters of Type 3 CLs were approximately 1 mm,
      and these CLs contained collagen fibers among their luteal cells, which suggests
      that this type of CL had regressed. The 3 types of CLs showed different reactions
      to Ob-R, with positive staining in Type 1, much less positive staining in Type 2
      and nearly negative staining in Type 3. In bears having CLs with functional and
      regressive features (Type 1 and 2 CLs), Ob-R was also immunolocalized in the
      developed glandular and ductal endometrial epithelium. In contrast, the Ob-R was
      absent in the undeveloped endometrial epithelium in bears with regressed (Type 3
      CLs) or no CLs. These findings suggested that leptin directly targets CLs and the
      endometrium so as to develop and maintain them during the delayed implantation
      period in Japanese black bears.

PMID- 19106489
TI  - Long-term treatment with bromocriptine inhibits endometrial adenocarcinoma
      development in rats.
AB  - The effects of long-term blockade of prolactin (PRL) action by bromocriptine
      (BRC) treatment on uterine carcinogenesis and on related ovarian physiology were
      investigated using a rat uterine cancer model. Ten-week-old cycling female Donryu
      rats, a high yield strain for uterine corpus tumors (endometrial
      adenocarcinomas), were treated with N-ethyl-N'-nitro-N-nitrosoguanidine (ENNG),
      as a tumor initiator, and injected with 1 mg/kg body weight BRC subcutaneously 4
      times per week until 14.5 months of age to block the proestrus PRL surge. The
      study was terminated at 15 months of age, and the results showed that long-term
      BRC treatment significantly inhibited endometrial adenocarcinoma development in
      terms of both incidence (34.6% to 13.0% with significant difference at 5%) and
      multiplicity (0.35 to 0.18 with significant difference at 5%), which indicates
      the number of adenocarcinomas per animals. While BRC did not affect estrous
      cyclicity in the treated animals, a significant decline was evident in the serum
      17 beta-estradiol (E2) to progesterone (P) ratio (E: P ratio), and the serum E2
      level showed a decreased tendency at 15 months of age. While the precise pathway
      to the inhibitory effect could not be determined; the pathway by which ovarian
      hormonal imbalance decreases the serum E: P ratio most likely plays a crucial
      role.

PMID- 19106490
TI  - Risk-adjusted analyses of the effects of hospital and surgeon volumes on
      postoperative complications and the modified Rankin scale after clipping of
      unruptured intracranial aneurysms in Japan.
AB  - The present study conducted risk-adjusted analyses to investigate the impacts of
      hospital and surgeon volumes on postoperative complications and the modified
      Rankin scale (mRS) after intracranial clipping of unruptured aneurysms, and to
      discuss the efficacy of relevant policy changes. Among 107 Japanese institutions,
      physician-reported data for 702 unruptured aneurysm patients were registered
      between December 2006 and April 2007. Postoperative complications and the mRS at
      the time of discharge were independently regressed against hospital and surgeon
      volumes, aneurysm size, aneurysm location, and comorbidities. Aneurysm size was a
      significant predictor of the overall outcomes. After adjusting for prominent
      confounders, hospital volume did not show any significant associations with
      postoperative complications (odds ratio [OR] 0.75, 95% confidence interval [CI]
      0.34-1.68, p = 0.49) or the mRS (OR 0.60, 95% CI 0.19-1.93, p = 0.39). Higher
      surgeon volume (>or=100) was associated with lower mRS scores (OR 0.40, 95% CI
      0.20-0.83, p = 0.013), but had no significant relationship with postoperative
      complications (OR 0.72, p = 0.47). Our risk-adjusted analyses showed no
      significant relationships between hospital volume and comorbidities. Therefore,
      the justification for hospital volume-based policies remains unclear. Prospective
      risk-adjusted volume-based studies are required for future evidence-based
      referral policies.

PMID- 19106491
TI  - Edaravone (MCI-186) scavenges reactive oxygen species and ameliorates tissue
      damage in the murine spinal cord injury model.
AB  - The present study evaluated the effect of the free radical scavenger edaravone on
      lesion volume and neurological dysfunction after spinal cord injury (SCI) in
      mice, and investigated its protective effects on superoxide generation. Female
      C57BL/6 mice were subjected to SCI using a pneumatic impact device and were
      treated with 3 mg/kg of edaravone or vehicle 30 minutes before the insult. Motor
      functions were quantitatively evaluated. Lesion volume was assessed by Dohrmann's
      two-cone method after one week. In situ detection of superoxide in the injured
      cord was carried out using the superoxide-sensitive dye dihydroethidium (DHE)
      staining technique. Pretreatment with edaravone significantly improved motor
      dysfunction and reduced the lesion volume to about 63% of the control (p < 0.05).
      Semi-quantitative measurements of red fluorescence emitted from DHE revealed that
      the superoxide concentration increased in the lesion periphery at 1 and 3 hours
      after the insult, and that pretreatment with edaravone significantly inhibited
      the increase of superoxide concentration in the lesion periphery at both time
      points (p < 0.0001). Double staining with DHE and monoclonal antibody against
      MAP2 showed that most cells positive for DHE were also positive for MAP2. These
      findings suggest that edaravone ameliorates tissue damage by scavenging reactive
      oxygen species, especially in the neurons, after SCI.

PMID- 19106492
TI  - Long-term seizure outcome in patients undergoing resection of lesions detected by
      magnetic resonance imaging.
AB  - The long-term efficacy of resective surgery was investigated in patients with
      lesions detected by magnetic resonance (MR) imaging. Thirty of 47 patients who
      had undergone lesionectomy between 1987-2001 were followed up by questionnaire.
      Patients with extratemporal resections outnumbered those with temporal lobe
      resections. The mean follow-up period was 12.4 +/- 3.7 years. Outcomes were
      graded according to Engel's criteria, and an arbitrary seizure outcome score was
      given for quantitative assessment. The mean seizure outcome scores were
      significantly lower in the early childhood (less than 3 years) onset group than
      in the late childhood (3 to 15 years) onset group, and significantly lower in the
      extratemporal resection of the cortical dysplasia group than in the temporal
      resection and the extratemporal resection of non-cortical dysplasia groups. This
      study indicated that lesionectomy based on MR imaging findings in patients with
      intractable epilepsy achieved effective long-term seizure control, and the
      outcome was related mainly to the pathology of the epileptogenic lesions and the
      temporal or extratemporal location.

PMID- 19106493
TI  - Carpal tunnel syndrome: electrophysiological grading and surgical results by
      minimum incision open carpal tunnel release.
AB  - The safety and effectiveness of the minimum incision technique were assessed in
      138 hands of 108 consecutive patients with carpal tunnel syndrome treated from
      April 1, 1997 to March 31, 2006. Clinical and electrophysiological examinations
      were conducted before and after surgical decompression. All hands were divided
      into early, mild, moderate, and severe groups based on preoperative
      electrophysiological severity. We examined the surgical outcomes of the affected
      hands in each group. Nocturnal or daytime dysesthesia, which had been present in
      132 (96%) of the 138 hands preoperatively, was completely relieved in 124 (94%)
      of the 132 hands. Complete relief was achieved in 7 (100%) of the 7 hands in the
      early group, 68 (99%) of the 69 hands in the mild group, and 45 (94%) of the 48
      hands in the moderate group. Complete relief was achieved only in 4 (50%) of the
      8 hands in the severe group, and 3 (38%) of the 8 hands did not show any
      improvement. No painful or hypertrophic scar formation was observed in this
      series. Only 2 patients complained of postoperative scar discomfort after more
      than 12 months, which completely disappeared by 14 months after surgery. Minimum
      incision open carpal tunnel release is a safe and reliable procedure with a high
      rate of functional improvement and patient satisfaction. Postoperative results
      were satisfactory regardless of the degree of preoperative electrophysiological
      severity if preoperative sensory nerve action potentials were detected.

PMID- 19106494
TI  - Dural arteriovenous fistula in the anterior cranial fossa: four case reports.
AB  - Three of 4 cases of dural arteriovenous fistulas (DAVFs) in the anterior cranial
      fossa were detected incidentally by magnetic resonance (MR) imaging, and one case
      manifested as intracerebral hemorrhage. Cerebral angiography revealed fistulas
      located in the anterior cranial fossa. Three patients underwent surgery, and the
      fistulas were successfully obliterated. One patient with nonruptured DAVF
      requested conservative medical management. Incidental detection of asymptomatic
      or nonruptured DAVFs in the anterior cranial fossa has increased with the wider
      use of MR imaging. Increase in the size of a venous varix is the indicator for
      aggressive therapeutic intervention in a patient receiving conservative medical
      management for asymptomatic or nonruptured DAVFs in the anterior cranial fossa.

PMID- 19106495
TI  - Spontaneous closure of transverse sinus dural arteriovenous fistula: case report.
AB  - A 60-year-old man presented with transverse sinus dural arteriovenous fistula
      (AVF) manifesting as sudden onset of headache and nausea, which underwent
      spontaneous closure 5 years after the onset. Computed tomography on admission
      revealed small intraventricular hemorrhage in the right lateral ventricle. No
      intracranial vascular lesion was detected and magnetic resonance angiography was
      used at yearly follow up. Two years after the first admission, he suffered
      diplopia and cerebral angiography revealed transverse sinus dural AVF. Right
      pulsatile tinnitus occurred 4 years after the first admission. The symptoms
      suddenly disappeared 5 years after the first admission, and follow-up angiography
      showed disappearance of the dural AVF. The exact mechanism of the spontaneous
      occlusion of dural AVF remains unknown. This case of spontaneous transverse sinus
      dural AVF closure occurred without disruption of sinus patency, suggesting that
      thrombosis of the draining veins into sinuses was not involved.

PMID- 19106496
TI  - Cavernous malformation of the ventral midbrain successfully removed via a
      transsylvian-transpeduncular approach: case report.
AB  - A 37-year-old woman presented with a rare cavernous malformation of the ventral
      midbrain with brainstem hemorrhage manifesting as sudden onset of headache and
      vomiting. The lesion was removed successfully through a transsylvian approach and
      a medial peduncular route. Postoperatively, her oculomotor nerve paresis worsened
      temporarily, but diplopia disappeared 2 months after surgery. We recommend the
      transsylvian-transpeduncular approach if the lesion is located in the ventral
      midbrain and faces the ventral surface of the brainstem, because of the effective
      access with minimal neurological deficits.

PMID- 19106497
TI  - Pineal germinoma with a prominent epithelioid cell granuloma component: case
      report.
AB  - A 20-year-old man presented with a rare case of germinoma with a large component
      of epithelioid cell granuloma manifesting as oscillopsia. Magnetic resonance
      imaging demonstrated a mass in the pineal region with homogeneous enhancement
      with gadolinium. Craniotomy was performed, ending in biopsy. The initial
      histological diagnosis was epithelioid cell granuloma, but systemic investigation
      detected no evidence of granulomatous disorder. A revised diagnosis of germinoma
      was based on positive immunohistochemical staining for placental alkaline
      phosphatase (PLAP) and c-kit. Histological diagnosis is sometimes incorrect if
      granulomatous reaction is dominant. Immunohistochemical staining for PLAP and c
      kit should be performed if germinoma is clinically suspected.

PMID- 19106498
TI  - Extradural pneumatocele after temporal craniotomy: case report.
AB  - A 22-year-old female first presented with a fibrillary astrocytoma in the left
      temporal region manifesting as complex partial seizure. She underwent left
      temporal craniotomy to remove the tumor. Surgery was uneventful, but she began to
      experience a blocked feeling in the left ear after surgery. Computed tomography
      (CT) obtained 3 weeks after surgery revealed persistent extradural air
      collection, which developed into an enlarged extradural air mass on follow-up CT
      obtained 8 months after surgery. She underwent additional surgery for
      obliteration of the pneumatocele by sealing the mastoidal fenestration with
      abdominal fat. She reported resolution of the symptom postoperatively. Extradural
      pneumatocele following temporal craniotomy is extremely rare, but is a possible
      surgical complication of opening of the mastoid sinuses.

PMID- 19106499
TI  - Extraforaminal lumbar synovial cyst causing sudden foot drop: case report.
AB  - A 52-year-old female presented with extraforaminal lumbar synovial cyst at the L4
      5 level causing sudden foot drop on the right. Computed tomography, magnetic
      resonance (MR) imaging, and coronal MR myelography source images identified the
      cystic mass in the extraforaminal zone. The patient underwent microdecompression
      via a lateral transmuscular route, and the extraforaminal cyst compressing L4
      ganglion was successfully removed. The histological diagnosis was synovial cyst.
      This unique case of surgically proven extraforaminal lumbar synovial cyst causing
      sudden foot drop indicates that extraforaminal synovial cyst should be included
      in the differential diagnosis of patients presenting with sudden foot drop.

PMID- 19106500
TI  - Modified three-dimensional skull base model with artificial dura mater, cranial
      nerves, and venous sinuses for training in skull base surgery: technical note.
AB  - Experience with dissection of the cavernous sinus and the temporal bone is
      essential for training in skull base surgery, but the opportunities for cadaver
      dissection are very limited. A modification of a commercially available prototype
      three-dimensional (3D) skull base model, made by a selective laser sintering
      method and incorporating surface details and inner bony structures such as the
      inner ear structures and air cells, is proposed to include artificial dura mater,
      cranial nerves, venous sinuses, and the internal carotid artery for such surgical
      training. The transpetrosal approach and epidural cavernous sinus surgery
      (Dolenc's technique) were performed on this modified model using a high speed
      drill or ultrasonic bone curette under an operating microscope. The model could
      be dissected in almost the same way as a real cadaver. The modified 3D skull base
      model provides a good educational tool for training in skull base surgery.

PMID- 19106501
TI  - [Study on adjuvant MTX-5-FU intraperitoneal chemotherapy for advanced gastric
      cancer].
AB  - The intraperitoneal administration of anti-cancer drug is a rationale route to
      adjuvant chemotherapy. We applied adjuvant MTX-5-FU intraperitoneal chemotherapy
      for 60 advanced gastric cancer cases which had undergone gastrectomy (Stage II
      18, Stage III A 19, Stage IIIB 13, and Stage IV 10 cases). A 5-year survival rate
      of Stage II, III A, IIIB and IV was 66.2%, 60.7%, 46.5% and 18.8%, respectively.
      Five-year survival rates of both Stage III A and IIIB on this study were likely
      to be higher than the rates of Stage III A and IIIB of other institutions. The 24
      out of 42 cases with the serosal surface exposure of cancer demonstrated a cancer
      recurrence. Seventy percent (17 cases) of the 24 recurred cases developed a
      peritoneal recurrence, which means that the intraperitoneal chemotherapy did not
      touch a pattern of the recurrence of the gastric cancer with the serosal surface
      exposure.

PMID- 19106502
TI  - [Clinical trials of neo-adjuvant chemotherapy for advanced gastric cancer with
      peritoneal dissemination].
AB  - Since 2000, we have introduced pre-operative chemotherapy including intra
      peritoneal chemotherapy to patients with positive cytology and with no non
      curative factors except peritoneum. Since 2006, we have started phase I trial
      with S-1 and intra-peritoneal chemotherapy with docetaxel to improve the efficacy
      and safety of the pre-operative regimen for advanced gastric cancer with
      peritoneal dissemination. The combination therapy with local and systemic
      chemotherapy is a promising regimen for gastric cancer with peritoneal
      dissemination.

PMID- 19106503
TI  - [Clinical significance of chemotherapy and chemo-radiotherapy in patients with
      metastatic esophageal cancer].
AB  - PURPOSE: We investigated the clinical significance of chemo-radiotherapy (CRT)
      and chemotherapy (CT) in patients with primary metastatic esophageal cancer.
      PATIENTS AND METHODS: Twenty-six patients with esophageal cancer received CRT (n
      =21) or CT alone (n=5) as a first treatment for para-aortic lymph node and/or
      hematogenous metastases. The therapeutic effect, duration of treatment, changes
      in performance status before and after treatment, and survival were analyzed
      retrospectively. RESULTS: The median duration of treatment was 2.9 months for CRT
      and 2.3 months for CT. The response rate was 76% in patients who underwent CRT
      and 20% in patients who underwent CT. In 18 patients (69%), the level of
      performance status showed no change after treatment in comparison with that
      before treatment. The median survival time was 5.6 months after CRT and 5.8
      months after CT (p=0.91). CONCLUSION: These results suggest that the majority of
      patients with extremely advanced esophageal cancer can tolerate CRT or CT well
      without compromising their performance status within their limited life
      expectancy.

PMID- 19106505
TI  - [Anti-VEGF therapy for peritoneal dissemination model of gastric cancer
      considering of pharmacokinetics].
AB  - Vascular Endothelial Growth Factor (VEGF) plays an important role in
      proliferation of cancer cells, angiogenesis and vascular permeability in
      peritoneal dissemination. Now we investigated the efficacy of anti-VEGF therapy
      in peritoneal dissemination of gastric cancer considering of pharmacokinetics. We
      investigated pharmacokinetics of bevacizumab, humanized anti-VEGF monoclonal
      antibody in subcutaneous xenograft and peritoneal dissemination model of OCUM
      2MD3, highly peritoneal-seeding cell line of human scirrhous gastric carcinoma.
      In the group of intraperitoneal administration, bevacizumab remains in the
      intraperitoneal cavity and transits slowly to blood pool. On the other hand, in
      the group of subcutaneous administration, bevacizumab transits faster to blood
      pool and is accumulated in subcutaneous tumors and peritoneal nodules.
      Bevacizumab administered intraperitoneally seemed to neutralize intraperitoneal
      VEGF. Bevacizumab administered in subcutaneous seemed to act on peritoneal wall
      and control vascular permeability. Systemic administration of anti-VEGF agent
      will be a potential therapy in peritoneal dissemination of gastric cancer.

PMID- 19106504
TI  - [A long-term survival case of gastric cancer with liver metastases treated by
      hepatic arterial infusion chemotherapy].
AB  - Although systemic chemotherapy has been recognized as a standard treatment for
      gastric cancer with synchronous hepatic metastasis, the survival benefit of the
      therapy is still unsatisfactory. On the other hand, the local effect of intra
      hepatic arterial chemotherapy (HAIC) is very high, and HAIC combined with
      systemic chemotherapy and surgery will be an effective therapy for selected
      patients. Here, we report a 39-year-old female case with advanced gastric cancer
      and synchronous liver metastasis. She has been treated with systemic
      chemotherapy, HAIC, and two operations. She has survived for 33 months now. The
      HAIC therapy will be a promising therapy in combination with systemic
      chemotherapy and/or surgery for gastric cancer with synchoromous liver
      metastasis.

PMID- 19106506
TI  - [Treatment for advanced gastric cancer with positive lavage cytology-systemic
      versus intraperitoneal chemotherapy].
AB  - The prognosis of advanced gastric cancer patients complicated with positive
      lavage cytology is poor, similar with that of peritoneal dissemination. For these
      diseases, we had reported the usefulness of intraperitoneal chemotherapy with
      cisplatin. Recently, systemic chemotherapy with S-1 and cisplatin is effective
      even for gastric cancer with peritoneal dissemination. Therefore, we compared the
      combination chemotherapy of S-1 and intraperitoneal cisplatin (IP group) with
      systemic S-1 plus cisplatin chemotherapy (IV group) for positive lavage cytology
      without peritoneal dissemination (P0CY1) gastric cancer. In this trial, 8
      patients were enrolled after gastrectomy. Four were IP group and another 4 were
      IV group. The average chemotherapy courses for IV group and IP group are 3.5
      times and 4.8 times, respectively. There was no difference in prognosis. Grade
      3/4 events occurred for IV group and IP group were 3 patients and only 1 patient,
      respectively. The combination chemotherapy of S-1 and intraperitoneal cisplatin
      was found to be well tolerated and effective in patients with advanced gastric
      cancer with P0CY1.

PMID- 19106507
TI  - [The future of loco-regional treatment for advanced gastric cancer].
AB  - We have evaluated the result of neo-adjuvant chemotherapy for advanced gastric
      cancer to estimate the future of loco- regional therapy. Twenty patients with
      advanced gastric cancer accepted 2 courses of neo-adjuvant chemotherapy with S- 1
      and cisplatin. In 13 patients (52%), chemotherapy could successfully control the
      growth of tumor. Thirteen patients with curative resection demonstrated a better
      survival (MST 682 days) than 12 patients with non-curative resection (MST 377
      days). Neo-adjuvant chemotherapy using S-1 and cisplatin was an effective
      treatment for advanced gastric cancer. However, no survival benefit could be
      obtained for patients with non-curative resection. Administration of loco
      regional treatment, such as intra peritoneal paclitaxel, should be considered for
      those cases with positive peritoneal cytology.

PMID- 19106508
TI  - [Third-line treatment of intermittent hepatic arterial infusion for unresectable
      liver metastases from colorectal cancer].
AB  - We report 6 cases of liver metastases from colorectal cancer with third-line
      treatment of intermittent hepatic arterial infusion and systemic chemotherapy for
      unresectable liver metastases with clinical signification of direct invasion to
      adjacent organs in Stage IV colorectal cancer. Subjects were 19 consecutive
      patients who underwent R0 surgery to the primary tumor for colorectal carcinoma,
      pT4, M1 in 1995-2003. We studied the relationship of pathological invasion to
      adjacent organs of tumor to other clinicopathological factors to prognosis. Of
      the 19 patients, 11 (57.8%) were R0 surgery to the tumor of metastases. Only 4
      (36.7%) patients survived more than 3 years. The patient without excision did not
      survive for three years. The median survival time was only 8.5 months.
      Multivariate analysis indicated that only R0 surgery to the tumor of metastases
      was an independent prognostic factor. The optimum resection for adjacent organs
      may prolong a survival. But the extended resection is a possibility of shortening
      the survival time.

PMID- 19106509
TI  - [Our experiences of preoperative chemo-radiotherapy for T4 primary rectal
      cancer].
AB  - We reviewed 7 cases of clinical record with preoperative chemo-radiotherapy to
      evaluate the clinical effectiveness of the chemo-radiotherapy for T4 rectal
      cancer. The preoperative radiation therapy consisted of 40-45 Gy delivered in
      fractions of 1.8-2.0 Gy per day, five days a week. A treatment of 5-fluorouracil,
      500 mg/body per day intravenously, or oral UFT-E (300 mg/m2) with l-leucovorin
      (75 mg) per day, or oral S-1 (80 mg/m2) per day five days a week, was given
      during radiotherapy. Grade 1 or 2 adverse effects occurred in 3 patients during
      chemo-radiotherapy, but the completion of chemo-radiotherapy was achieved in all
      of the 7 patients. Tumor invasion identified by CT and MRI to other organs in the
      pelvis disappeared in four cases with complete or partial response after a month
      of chemo-radiotherapy. Although the other organs were also removed during surgery
      in 4 patients, curative surgery was performed in 5 patients. There was no
      histological invasion seen to other organs in 4 patients, and one patient had
      histological complete disappearance of tumor. Although complications after
      surgery were found in all of the patients, they were improved by conservative
      treatment. One of 4 patients with curative surgery had liver and local
      recurrence, but others survived without recurrence. Preoperative chemo
      radiotherapy was expected to be a safe and effective treatment to improve the
      resection rate and prognosis for T4 rectal cancer.

PMID- 19106510
TI  - [Chitin/cisplatin--an adhesive anticancer drug].
AB  - The authors devised an adhesive anticancer drug delivery system using 70%
      deacetyalated chitin (DAC-70) and cisplatin (CDDP). We prepared two different
      types of the drug carriers; namely, DAC-70 viscous solution and DAC-70
      lyophilized granules, which easily provided viscous solution when mixed with a
      liquid. We then formed a novel CDDP-loaded system by mixing each vehicle with
      CDDP solution. Each product showed a stronger tissue-adhesive force at 37 degrees
      C than that of 25 degrees C. More than 90% of total CDDP was released from the
      system within 24 hours. A large amount of the CDDP released from the system
      revealed it to be free CDDP when the DAC granule was used as the carrier, while
      the amount of free CDDP was less than 20% in the case of the DAC viscous
      solution. When the DAC-CDDP solution was given into the peritoneal cavity of
      rats, the CDDP remained there and only a little was transferred into the
      peripheral blood. We could also provide loco-regional pleurodesis by injecting
      the novel solution into the rat pleural cavity. These data suggest that our newly
      devised system has a great potential in cancer chemotherapy for the patients with
      malignant pleural effusion and ascites.

PMID- 19106512
TI  - [The significance of combined treatment for hepatocellular carcinoma with partial
      splenic embolization and transcatheter arterial chemoembolization using IA
      call/lipiodol].
AB  - BACKGROUND AND AIM: Partial splenic embolization (PSE) is often performed to
      improve thrombocytopenia in liver cirrhotic patients. The aim of this study was
      to evaluate the efficacy and safety of PSE in combination with trans-catheter
      arterial chemoembolization (TACE) for hepatocellular carcinoma (HCC). PATIENTS
      AND METHODS: From January 2004 to December 2007, 8 HCC patients associated with
      hypersplenism caused by cirrhosis were synchronously treated with TACE and PSE.
      Fifteen patients with TACE alone at the same period were enrolled as a control.
      Follow-up examinations included a calculation of peripheral blood cells
      (leukocytes and platelets), liver damage, duration until recovery, and treatment
      associated complications. RESULTS: Initially, there were no significant
      differences in sex, age, Child-Pugh grade and peripheral blood cell counts
      between two groups. After treatment, leukocyte and platelet counts were
      significantly higher in PSE combined with TACE group during the follow-up period
      than TACE group (p<0.01). Severe complications never occurred in both groups.
      CONCLUSION: PSE combined with TACE is more effective than TACE alone for patients
      with HCC associated with hypersplenism caused by cirrhosis.

PMID- 19106511
TI  - [Pilot study of neo-adjuvant chemotherapy involving intraperitoneal
      administration of paclitaxel and oral S-1 for patients with T3 gastric cancer].
AB  - The prognosis of patients with T3 gastric cancer is poor, even if a curative
      resection is performed. Novel combination neo-adjuvant chemotherapy has been
      introduced for T3 gastric cancer patients. This pilot study involving 5 patients
      was performed between December 2002 and March 2003. They were diagnosed with
      gastric cancer with serosal invasion (T3) without P1 and CY1 by staging
      laparoscopy. We selected a combined chemotherapy with both paclitaxel and S-1.
      Paclitaxel at 60 mg/m2 was administered intraperitoneally on days 1 and 8, and S
      1 at 80 mg/m2 was administered orally for 14 days followed by a 7-day-rest, as
      one course. After one course of this therapy, surgery was performed. The plasma
      concentration of paclitaxel was measured in two patients. Toxicites were
      generally mild, and no serious adverse reactions were observed. The plasma
      concentration of paclitaxel was about 100 ng/mL in the period of 1-6 hours after
      the administration. After one course, four patients underwent a total gastrectomy
      and one distal gastrectomy. The final histological stagings were included one
      stage IB, one stage II, one stage IIIA, one stage IIIB, and one stage IV. Three
      patients died at 10, 11, and 16 months after the initial treatment, and two have
      survived for 64 and 62 months. As the intraperitoneal administration of
      paclitaxel and oral S-1 was well-tolerated, further studies should be conducted
      involving T3 gastric cancer patients.

PMID- 19106513
TI  - [A case of esophageal cancer patient who developed tumor lysis syndrome after
      chemotherapy].
AB  - We report here a case of esophageal cancer patient who developed tumor lysis
      syndrome after chemotherapy. A 57- year-old man received esophagectomy for
      advanced esophageal cancer. CT study revealed multiple lymphnode metastases,
      multiple bone metastases and multiple lung metastases after 15 months from the
      operation. So, chemotherapy was performed for the patient. Eleven days following
      the administration of docetaxel: 30 mg/m2 and nedaplatin: 30 mg/m2, the patient
      developed TLS (serum creatinine: 8.57 mg/dL, uric acid: 11.0 mg/dL, serum
      potassium: 6.3 mEq/L, serum phosphorus: 7.18 mg/dL). The patient responded well
      to an appropriate treatment with a combination of vigorous intravenous hydration,
      carperitide, allpurinol and potassium citrate sodium citrate. This case report
      describes the first patient to develop TLS following chemotherapy for esophageal
      cancer.

PMID- 19106514
TI  - [A case of advanced cervical esophageal cancer with liver cirrhosis and diabetes
      mellitus showing a complete response by radiation therapy after the operation for
      multiple esophageal cancers].
AB  - We report a case of advanced cervical esophageal cancer with liver cirrhosis and
      diabetes mellitus that was successfully treated by radiotherapy after the
      operation for multiple esophageal cancers. The patient was a 69-year-old man with
      the diseases, who underwent the operation 6 years ago, and had been under a
      follow-up as an outpatient. Upper digestive tract endoscopic examination revealed
      an advanced cervical esophageal cancer. We performed radiotherapy because he had
      the diseases, furthermore his performance status was 2 (ECOG). The total
      irradiation was 59 Gy, and a complete reduction was obtained. Thirty months after
      the treatment, the patient shows no sign of recurrence. These results suggest
      that radiotherapy is an effective treatment for advanced esophageal cancer with a
      poor general condition.

PMID- 19106515
TI  - [Four cases of recurrent esophageal cancer with tracheal invasion treated by a
      placement of tracheal stent].
AB  - Frequently advanced or recurrent esophageal cancer was invasive trachea and
      occurred with hemoptysis or dyspnea. Occasionally, these cases were treated by a
      placement of tracheal stent for hemostasis and an establishment of airway for
      life saving. We experimented the four cases of recurrent esophageal cancer with
      tracheal invasion treated by a placement of tracheal stent. These 4 cases were
      for patients treated with no prior chemotherapy (CRT) had a better prognosis and
      quality of life (QOL) than the patient with a placement of tracheal stent after
      CRT. Therefore, the patient without CRT was a good indication to a placement of
      tracheal stent. However, even if the patient of previously performed CRT, it was
      important and effective treatment that a placement of tracheal stent was avoided
      the state of lethal condition with dyspnea.

PMID- 19106516
TI  - [A case of esophageal cancer with recurrent lymph-node metastasis successfully
      treated with chemo-radiotherapy after mediastinoscopy-assisted transhiatal
      esophagectomy].
AB  - A 63-year-old man who was diagnosed T1b esophageal cancer, for which
      transthoracic esophagectomy was indicated, received mediastinoscopy-assisted
      transhiatal esophagectomy because of the previous right thoracotomy for pulmonary
      tuberculosis. CT study revealed an upper mediastinal lymph-node metastasis 3
      years after surgery. He was treated with chemotherapy of daily continuous 5-FU
      infusion (500 mg/day) and daily nedaplatin (5 mg x 5 days/week) for 4 weeks
      combined with concurrent radiotherapy (44 Gy). A partial response was achieved
      for the metastatic lymph-node lesion after chemo-radiotherapy, so boost
      radiotherapy (16 Gy) was given to the patient. He is still alive now without a re
      growth of the lymph-node metastasis. It is important to follow-up the patient
      with advanced esophageal cancer carefully who received mediastinoscopy-assisted
      transhiatal esophagectomy.

PMID- 19106517
TI  - [A case of stenosis of the reconstructed jejunum due to recurrent cancer after
      total gastrectomy in which stent-in-stent placement was effective].
AB  - OBJECTIVES: We report one case of stenosis of the reconstructed jejunum due to
      recurrent cancer after total gastrectomy in which stenting was effective and good
      QOL was achieved. CASE: The patient was a 70-year-old woman. In July 2000, the
      patient underwent total gastrectomy.Roux-en Y reconstruction with a diagnosis of
      gastric cancer. The pathological diagnosis was U-Post, Type 3, por 1, T3, N1, H0,
      P0, CY0, M0, and Stage IIIA. From 9 months after the operation, aphagia occurred
      and stenosis of the reconstructed jejunum was noted. Based on a biopsy of the
      stenosis, a diagnosis of post-operative recurrent gastric cancer was made.
      Although the patient received two cycles of low-dose FP therapy, complete
      response was not obtained, and the patient stayed at home under the IVH control
      for about 4 months. In June 2001, the patient was hospitalized for a stent
      placement due to the patient's request. METHOD: After a guide wire was
      endoscopically inserted and a good passage on the anal side of the stenosis was
      confirmed, a stent was placed. Self Expandable Metallic Stent (SEMS) was used.
      CLINICAL COURSE: Following the stent placement, the patient was able to ingest
      orally, but 6.5 months later, stenotic symptoms developed and another stent was
      deployed (stent in stent). CONCLUSION: Stenting is relatively simple and less
      invasive, which is useful for the improvement of QOL and in recurrent cases as
      well.

PMID- 19106518
TI  - [A case of advanced gastric cancer responding to S-1/paclitaxel was
      pathologically complete response].
AB  - A 63-year-old man was found to have advanced gastric cancer and staging
      laparoscopy revealed positivity of peritoneal washing cytology. Since curative
      surgery was deemed not possible, we started chemotherapy using S-1 (80 mg/m2)
      orally administered for 2 weeks and paclitaxel (50 mg/m2) administered
      intravenously on days 1 and 8. After 3 courses of chemotherapy, the primary
      lesion and regional metastatic lymph node were diminished by CT. We confirmed a
      peritoneal washing cytology negative by laparoscopic examination. We performed a
      total gastrectomy and dissection of regional lymph node (D2). Pathologically,
      cancer cells disappeared both in the main tumor and lymph nodes, and histological
      efficacy was evaluated as grade 3. Adjuvant chemotherapy was done with same
      regimen, and he has had no recurrence as of 15 months after surgery.

PMID- 19106519
TI  - [A case of AFP producing gastric cancer for which radiation therapy was effective
      in paraaortic lymph node recurrence].
AB  - The patient was a 75-year-old woman, who was diagnosed with type 3 gastric
      cancer. Total gastrectomy with D2-#10 lymph node dissection and partial hepatic
      resection was performed. Histological findings showed it to be stage IV
      (pT2N1M0P0CY0H1) and AFP producing gastric cancer. After the operation, liver
      metastasis was found, and RFA, partial hepatic resections, hepatic intra-arterial
      infusion chemotherapy (5-FU, CDDP), intravenous chemotherapy (docetaxel,
      paclitaxel, CPT-11) were applied. Although liver metastasis was disappeared,
      paraaortic lymph node recurrence appeared, and chemotherapy was not effective.
      Radiation therapy (2 Gy/day, total 50 Gy) for paraaortic lymph node metastasis
      was performed. The metastatic node underwent complete remission following a
      radiation therapy. Three years and six months passed since the first operation,
      and the patient has shown no signs of relapse. Therefore, our case suggests
      radiation therapy could be an effective treatment modality for the lymph node
      metastasis in AFP producing gastric cancer.

PMID- 19106520
TI  - [Adjuvant chemotherapy of S-1 and CDDP for undifferentiated adenocarcinoma of the
      stomach].
AB  - A 67-year-old female visited our department complaining a general fatigue.
      Gastrointestinal endoscopy revealed a giant ulcer at distal portion of the
      stomach. NSE was the only tumor marker showing an abnormal value. Pathohistology
      of the biopsy specimen showed a monotonus massive growth of small irregular tumor
      cells. Distal gastrectomy with regional lymph node dissection was carried out.
      Final pathology report was undifferentiated adenocarcinoma of the stomach,
      exposing itself to serosa with lymph node metastasis. Postoperative chemotherapy
      was started using S-1. However, despite NSE turning normal, CEA rose that CDDP
      was added to the regimen. She went into remission for several months but CEA rose
      again and CDDP was changed to CPT-11. To our great regret, she died six months
      after the operation. Undifferentiated adenocarcinoma of the stomach is rare
      disease. Immunohistochemical staining is useful for a differential diagnosis.
      Prognosis is said to be poor but S-1/CDDP may contribute to prolong prognosis.

PMID- 19106521
TI  - [A case of advanced gastric cancer treated with chemo-radiotherapy as the fourth
      line therapy].
AB  - A 69-year-old female patient with type 2 advanced gastric cancer (s
      T4N0M0H0Cy0P0, f-Stage IIIA) located from lower corps to antrum underwent a
      distal gastrectomy with D2 lymphandectomy in May 2006. After surgical treatment,
      S-1+ docetaxel combined chemotherapy was started for pEM (+) due to direct
      invasion to pancreas head as the first-line chemotherapy. However, the local
      recurrence whose diameter was 24 mm at pancreas head was detected with enhanced
      CT in December 2006. Moreover, nevertheless CPT-11+CDDP combined chemotherapy or
      paclitaxel monotherapy as the second or the third-line chemotherapy,
      respectively, the diameter of the local recurrence enlarged to 38 mm in November
      2007. Therefore, chemo-radiotherapy using with S-1 and CDDP was started in
      December 2007 and the diameter of local recurrence was reduced to 25 mm in
      January 2008. No adverse event of grade 3 or more occurred during chemo
      radiotherapy except for grade 3 of neutropenia. Chemo-radiotherapy for this
      gastric-cancer patient with local recurrence of multiple anti-tumor drug
      resistance was effective and safe.

PMID- 19106522
TI  - [A case of liver and lung metastases in gastric cancer successfully treated with
      S-1 and paclitaxel mono-therapy].
AB  - A 65-year-old male underwent a curative distal gastrectomy for advanced gastric
      cancer in June 2000. S-1 mono- therapy (80 mg/m2, day 1-28/42 days) for liver
      metastasis in S6 started as the first-line chemotherapy in October 2004. After 3
      courses, complete response (CR) was observed for liver metastasis which had
      continued until January 2007. During the first-line chemotherapy, grade 2 non
      hematological toxicities occurred and the S-1 dose reduction was required.
      Thereafter, no more grade 2 non-hematological toxicities were observed.
      Paclitaxel mono-therapy (80 mg/m2, day 1, 8, 15/28 days) for multiple lung
      metastases started as the second-line chemotherapy in February 2007. After 4
      courses, complete response (CR) was observed for lung metastasis which has
      continued until now, May 2008. During the second- line chemotherapy, grade 3
      neutropenia and grade 2 leukopenia occurred and a 10% dose reduction of
      paclitaxel was required three times. Consequently, the hematological toxicities
      have not occurred.

PMID- 19106523
TI  - [A case of unresectable advanced gastric cancer successfully treated with
      continuous S-1 + CPT-11 chemotherapy accompanied by dose reduction against grade
      4 hematological adverse event].
AB  - We report a successful case of chemotherapy accompanied with grade 4 adverse
      events for unresectable advanced gastric cancer. A 73-year-old man was admitted
      to our hospital with complaint of abdominal pain in July 2007. The detailed
      examination had revealed advanced gastric cancer, lymph node metastasis, and
      multiple hepatic metastases. Performance status (PS) was level 0, and oral intake
      of medications was possible. Combined therapy with S-1 and CPT-11 (IRIS regimen)
      was performed from August as the first-line therapy. As a consequence of first
      course, grade 4 hematological adverse events (AEs) appeared and an urgent
      hospitalization was required. With whole body supportive care against grade 3 non
      hematological AEs, which were diarrhea, anorexia, and fatigue, G-CSF, the broad
      spectrum antibiotic were administered at the clean-room. After 1 course, cyto
      reductive change was confirmed at the primary lesion and hepatic metastases. We
      continued the same regimen with dose reduction (S-1: 2 level dose down, CPT-11:
      10% dose down). Although the regression of hepatic metastases was seen, we
      repeated the dose reduction of CPT-11 and the dose down level was reached to 40%
      for prolonged grade 2 neutropenia. After 6th courses, complete responses at
      primary lesion, lymph node, and hepatic metastases were achieved. The patient has
      received the same regimen of 9th course continuously as an outpatient, and CR has
      been maintained.

PMID- 19106524
TI  - [Two cases of long-term survival with CY1, stage IV gastric cancer due to surgery
      and postoperative chemotherapy].
AB  - The first case is a man in his 30s with gastric cancer, of which clinical finding
      was T3N0M0P0M0 (Stage II), underwent a distal gastrectomy with D2
      lymphadenectomy. CY1 was detected during the operation and the final findings was
      T3N2M0H0P0CY1 (Stage IV). After the operation, we administered 120 mg/day of S-1
      for 38 months and the patient remains alive for 6 years and 2 months. The second
      case is a man in his 20s with gastric cancer, of which clinical finding was
      T3N0M0P0M0 (Stage IIIa), underwent a distal gastrectomy with D2 lymphadenectomy.
      CY1 was detected during the operation and the final findings was T3N2M0H0P0CY1
      (Stage IV). After the operation, we administered 120 mg/day of S-1 for 13 months
      and the patient remains alive for 6 years and 2 months. A combination gastrectomy
      with D2 lymphadenectomy and postoperative chemotherapy was considered to be a
      radical treatment for CY1, Stage IV gastric cancer.

PMID- 19106525
TI  - [A case of liver metastasis from gastric cancer successfully treated with radio
      frequency ablation therapy].
AB  - We report a case of liver metastasis from gastric cancer successfully treated
      with radio-frequency ablation therapy. The patient was a 63-year-old man whom we
      performed distal gastrectomy with D2 lymphnode dissection for type II gastric
      cancer on April 2004. A post operative pathological finding was pT2N1M0, Stage
      II. Therefore, the operation was evaluated to be as curative A. No adjuvant
      therapy was performed. After 11 months computed tomography showed a space
      occupied lesion (SOL) in S7 segment of the liver, we thought it to be as liver
      metastasis. We performed radio-frequency ablation therapy, and complete response
      was obtained. He is alive without a sign of recurrence for 30 months. We thought
      that radio -frequency ablation therapy was one of the useful treatments for liver
      metastasis from gastric cancer.

PMID- 19106526
TI  - [A case report of long-term survival of advanced gastric cancer (P1CY1) after
      gastrectomy].
AB  - A-57-year-old male was performed a total gastrectomy (f-T3N2H0P1CY1M0, Stage IV)
      for gastric cancer in 2004. We kept performing chemotherapies until the seventh
      line, and the patient at last had a long-term survival of 46 months after
      surgery. If we recognized a tumor that had a tendency to be progressive, the long
      term survival may be obtained by changing a regimen as early as possible.

PMID- 19106527
TI  - [A case of metachronous splenic metastasis from gastric cancer].
AB  - A 76-year-old woman underwent a total gastrectomy with dissection of second group
      of lymph nodes for type 2 gastric cancer at the back wall of the middle stomach
      body. The gastric cancer was moderately differentiated adenocarcinoma, which
      involved the second group of lymph nodes. Tumor makers increased-the CEA level
      became 10.7 ng/mL and the CA19-9 level became 110 U/mL after the operation. CT
      scan showed a solitary splenic tumor sized about 60 mm in diameter. No other
      prominent metastatic lesions were demonstrated, so that a splenectomy was
      performed in February 2008. Histopathologically the splenic tumor was
      adenocarcinoma, and was diagnosed as metastasis of gastric cancer. The report
      which excised asynchronism spleen metastasis of a stomach cancer after the
      operation is very rare. She remains recurrence free 4 months later.

PMID- 19106528
TI  - [Two cases of advanced gastric cancer with postoperative severe complications
      after neo-adjuvant chemotherapy].
AB  - We report two cases of advanced gastric cancer with severe postoperative
      complications after neo-adjuvant chemotherapy (NAC). The first case is a 60-year
      old man who was diagnosed as a type 2 advanced gastric cancer with paraaortic
      lymph node metastases and the elevation of serum CA19-9 level. NAC was started,
      but no reductions were noted after 3 courses. Palliative total gastrectomy with
      distal pancreatectomy, splenectomy, cholecystectomy, and partial hepatectomy for
      T4 gastric cancer exhibiting obstruction were performed in June 2007. On
      postoperative day 10, abdominal CT scan revealed left subphrenic abscess, then CT
      guided percutaneous drainage was performed. A culture of the abscess yielded
      Candida albicans and Candida glabrata. The second case is a 58-year-old man who
      was diagnosed as a type 2 advanced gastric cancer with multiple lymph node
      metastases and the elevation of serum CA19-9 level. NAC were performed, but no
      reductions were noted. A distal gastrectomy was performed in January 2008. On the
      first postoperative day, a severe abdominal distension was appeared suddenly and
      increasingly. An emergency laparotomy was undergone, but no findings of the bowel
      obstruction were observed. On postoperative day 2, a rise of serum beta-D-glucan
      level was recognized. Both cases were improved by an antifungal drug therapy.

PMID- 19106529
TI  - [Successful treatment of embolization and chemoradiationtherapy with S-1 for the
      advanced gastric cancer which was actively bleeding].
AB  - In the management of inoperable patients who have advanced gastric cancer, it is
      important to control an active tumor bleeding for the purpose of keeping the
      patient's quality of life well. We treated two patients: embolization with coil
      to aneurysm in the gastric tumor in one case, and embolization and
      chemoradiationtherapy with S-1 in the other. In results, we have never seen an
      active tumor bleeding and anemic state requiring a blood transfusion after the
      treatment. Both patients died from other diseases. We think these treatments are
      useful for patients with active bleeding in advanced gastric cancer.

PMID- 19106530
TI  - [A case of gastrointestinal stromal tumor of the stomach with rapid growth in a
      short term].
AB  - A 75-year-old man was admitted to our hospital with massive hematemesis. Upper
      gastrointestinal endoscopy revealed a submucosal gastric tumor with ulcer lesion,
      about 30 mm in diameter, in the anterior wall of the cardia. Pathological
      findings of biopsy specimens showed a gastrointestinal stromal tumor (GIST) of
      the stomach. Abdominal computed tomography (CT) showed an extramural low density
      mass, measuring 27 mm, in the cardia. From these findings, we thought we should
      be performing a wedge resection of the stomach for this tumor. After one month
      from the first examination, preoperative upper gastrointestinal endoscopy
      revealed a growth of the tumor. Abdominal CT also showed an obvious growth of the
      tumor, measuring 50 mm. Thus, laparoscopy-assisted proximal gastrectomy was
      performed, because the tumor was close to the cardia. Postoperative diagnosis of
      the tumor was pathologically confirmed to be a GIST with a high malignant
      potential. The case report of GIST that shows rapid growth for a short term is
      rare. We herein describe a case of GIST with rapid growth during one month before
      the operation.

PMID- 19106531
TI  - [A partial response to combined S-1 and CDDP chemotherapy enabling a curative
      resection in a patient with locally advanced duodenal cancer].
AB  - A 60-year-old male presented with a primary complaint of back pain. CT revealed a
      primary duodenal tumor with bulky lymph node metastases. Gastrofiberscopy
      revealed a primary duodenal tumor located the second portion. The patient was
      treated with combined chemotherapy using S-1 and CDDP to prior to performing a
      surgical curative resection. S-1 (80 mg/m2) was orally administered for 3 weeks
      (day 1-21), and CDDP (60 mg/m2) was simultaneously administered on day 8 every 5
      weeks. The chemotherapy was repeated for 2 cycles. The patient experienced no
      adverse event. CT revealed a partial response after chemotherapy. The patient
      underwent a curative pancreaticoduodenectomy. The pathological efficacy was Grade
      2. Adjuvant chemotherapy was provided using S-1 regimen because of its
      pathological efficacy and the absence of severe adverse events. Six months after
      the operation, the patient was doing well and showed no signs of recurrence of
      the cancer. This S-1/CDDP combination chemotherapy was therefore considered to be
      suitable as neo-adjuvant chemotherapy because it permitted the patient to
      subsequently undergo a curative resection, and thereby achieving a survival
      benefit for locally advanced duodenal cancer.

PMID- 19106532
TI  - [Management of pulmonary recurrence of hepatocellular carcinoma after receiving a
      living-donor liver transplantation--a case report].
AB  - We report on the treatment experience of five living-donor liver transplantation
      (LDLT) recipients for hepatocellular carcinoma (HCC) with pulmonary metastases.
      Between March 1998 and December 2007, five patients who underwent LDLT for HCC
      were identified with a routine follow-up of pulmonary metastases: Two patients
      underwent a radical resection for pulmonary recurrence of HCC, Two patients were
      only observed by palliative treatment, and one patient had chemotherapy using S
      1/IFN. The survival range from pulmonary recurrence of HCC was 7.5 to 43.0 months
      and the median survival time was 18.9 months. Only one of the 5 patients who
      underwent a surgical resection of pulmonary recurrence is still alive without a
      new recurrence for a long period of time.

PMID- 19106533
TI  - [A case of hepatocellular carcinoma with gall bladder metastasis].
AB  - A 74-year-old male was admitted to Osaka University Hospital for advanced
      hepatocellular carcinoma in April 2007. CT and MRI scan showed the tumor was
      located mainly in posterior segment and had portal vein tumor thrombus, and the
      wall of gall bladder was edematous and thick, but seemed not to be close to the
      main tumor. We performed an extended posterior segmentectomy, tumor thrombectomy
      and cholecystectomy. Pathological examination showed that poorly differentiated
      hepatocellular carcinoma cells, which were same as the main tumor, existed in
      lamina propria and muscle layer of gall bladder, and invaded the submucosal
      vessels. So we diagnosed it as gall bladder metastasis from hepatocellular
      carcinoma.

PMID- 19106534
TI  - [A long-term survival case of hepatocellular carcinoma recurrence after the
      patient received a living donor liver transplantation treated by combined
      modality therapy].
AB  - We report a case of hepatocellular carcinoma (HCC) recurrence after the patient
      received a living donor liver transplantation, which was treated by combined
      modality therapy. The patient survived for 67 months. A 61-year-old male was
      diagnosed as HCC with alcoholic cirrhosis and was transplanted the liver from a
      living donor. The number of tumors was about 50, the maximum tumor size was 3.3
      cm and histology of the tumor was poorly differentiated hepatocellular carcinoma
      with portal invasion (Vp2). HCC recurred at the peritoneum 12 months after the
      liver transplantation and was surgically resected. Then, multiple HCC recurred in
      the liver graft and the patient was treated by systemic chemotherapy, and local
      therapy such as RFA, PEIT and TAE. Now 67 months after the transplantation, he
      additionally has a HCC metastasis to the spleen and lung and is treated by
      combined modality therapy. This case suggested that a combined modality therapy
      might have improved the survival of the patient after recurrence in the liver
      transplantation for advanced HCC.

PMID- 19106535
TI  - [A long-term survival case of hepatocellular carcinoma with lymph node metastases
      treated with surgery and radiotherapy].
AB  - We report a long-term survival case of hepatocellular carcinoma with lymph node
      metastases treated with surgery and radiotherapy. A 71-year-old man was admitted
      to our department at Kumamoto University Hospital in May 2003 for a treatment of
      local recurrent HCC after transarterial chemoembolization. CT showed an
      infiltrative type tumor, 2.5 cm in diameter, in the segment 8 of the liver. We
      treated the liver tumor with a right paramedian sectionectomy in May 2003.
      Postoperatively, lymph node metastases and recurrent HCC were diagnosed. Three
      times of local ablation therapies for recurrent HCC, twice lymph node
      dissections, and twice radiotherapies for lymph node metastases were successfully
      achieved. The patient survived without recurrence for 60 months after the initial
      hepatectomy.

PMID- 19106536
TI  - [A case of combined hepatocellular and cholangiocarcinoma showing tumor growth
      and invasion to the diaphragm during interferon-alpha and 5-fluorouracil combined
      intra-arterial chemotherapy].
AB  - We report a case of combined hepatocellular and cholangiocarcinoma showing tumor
      growth and invasion to the diaphragm during interferon-alpha (IFN-alpha) and 5
      fluorouracil (5-FU) combined intra-arterial chemotherapy. A 63-year-old female
      was in hospital for treatment of hepatic tumor in left lobe with portal venous
      tumor thrombus. She was treated by IFN-alpha/5-FU chemotherapy, and the tumor was
      significantly reduced. For 28 months, the tumor was successfully treated by IFN
      alpha/5-FU chemotherapy. But, thereafter the abdominal computed tomography showed
      the tumor re-growth and invasion to the diaphragm. Then the patient underwent the
      tumor resection. The histological findings were consistent with combined
      hepatocellular and cholangiocarcinoma. Immunohistological examination revealed a
      heterogeneous expression of IFN-alpha receptor 2. This case suggested that the
      growth of cancer cells without sensitivity to IFN-alpha/5-FU chemotherapy and the
      blood supply via the diaphragm led the relapse of IFN-alpha/5-FU chemotherapy.

PMID- 19106537
TI  - [A case of successful combination therapy with trans-arterial embolization, trans
      arterial chemotherapy and radiofrequency ablation therapy].
AB  - A patient is a 78-year-old male. Abdominal ultrasound tomography revealed hepatic
      tumors. Abdominal computer tomography (CT) revealed a 5.5 cm-in-diameter low
      enhanced lesion and a 4.0 cm-in-diameter enhanced lesion at S8, and a 1.8 cm-in
      diameter enhanced lesion at S5, a 1.4 cm-in-diameter enhanced lesion at S6, which
      led to a diagnosis of combined hepatocellular carcinoma with intra-hepatic
      metastasis (IM2) in July 2007. From August to October 2006, he received a hepatic
      combination therapy with trans-arterial chemotherapy at a low enhanced lesion and
      trans-arterial embolization (TAE), and radiofrequency ablation therapy (RFA) at
      enhanced lesions. As of June 2008, this patient is still alive with no recurrence
      after 8 months from the beginning of this treatment. In conclusion, it might have
      been effective and suitable to combine multiple therapies to each of the tumor
      characteristics for mixed hepatocellular carcinoma.

PMID- 19106539
TI  - [A case of successful management of liver metastases of pancreatic carcinoma by
      hepatectomy and adjuvant chemotherapy].
AB  - We have experienced a successful case of liver metastases from pancreatic ductal
      adenocarcinoma treated by hepatectomy and adjuvant chemotherapy. A 62-year-old
      male had undergone pancreatoduodenectomy for pancreatic ductal adenocarcinoma.
      Thirty days after the surgery, he was given a systemic administration of
      gemcitabine (GEM) at a dose of 1,000-1,400 mg/body biweekly. Serum CA19-9 was
      elevated about 8 months after the primary resection. In addition, abdominal CT
      scan revealed a hepatic metastatic lesion about 10 month after the surgery, We
      changed the protocol of the chemotherapy to a systemic administration of GEM at a
      dose of 1,200-1,400 mg/body once a week for 3 weeks with a 1-week rest. Serum
      CA19-9 was more elevated, so he underwent hepatectomy for liver metastases from
      pancreatic ductal adenocarcinoma 13 months after the primary surgery, and the
      adjuvant chemotherapy of GEM restarted at 21 days after the hepatectomy. He has
      survived without recurrence more than 14 months after the hepatectomy.

PMID- 19106538
TI  - [A case of synchronous triple cancer involving advanced hepatocellular
      carcinoma].
AB  - We report herein a case of advanced hepatocellular carcinoma (HCC) with gastric
      cancer and rectal cancer. A 68-year-old man was diagnosed with advanced HCC and
      gastric cancer. At first, he was planned to be treated by trans-catheter arterial
      chemoembolization (TACE). After TACE, he was diagnosed with rectal cancer by
      following abdominal computed tomography (CT) and colonoscopy. Then, he was
      diagnosed with synchronous triple cancer. To avoid bleeding and obstruction, a
      resection of rectal cancer was performed secondly. After the surgery, he was
      treated by TACE for three times. HCC was well-controlled, but there remained a
      small active HCC lesion. Gastric cancer had little progressed, but was still
      resectable. Finally, we performed a partial hepatectomy and a distal gastrectomy
      simultaneously. Both of cancer stage and progression-related multimodal treatment
      is necessary in synchronous cancer.

PMID- 19106540
TI  - [A case of metastases of umbilicus (Sister Mary Joseph's nodule)].
AB  - We report a case of advanced unresectable pancreatic cancer (cT4N1M0/stage IVa).
      The patient was a 68-year-old man. Chemo-radiation therapy (CRT) with GEM (1,000
      mg/body) was administered once a week on days 1, 8 and 15 for 3 weeks. The
      radiotherapy dose was 45 Gy (1.5 Gy x 2/day, 15 days). After CRT, the patient was
      treated with a GEM+ UFT-E combination chemotherapy. When that was done, CT scan
      revealed metastases of umbilicus (Sister Mary Joseph's nodule) and the liver.
      Microwave Coagulation Therapy for the liver metastasis and tumorectomy for
      metastasis of umbilicus were performed. But he died after 4 months from the
      therapies.

PMID- 19106541
TI  - [A case report of intra-operative radiotherapy and gemcitabine for unresectable
      pancreatic body cancer].
AB  - We report an effective case of fifty-seven year-old female with unresectable
      pancreatic cancer. Its chief complaint of the case was epigastralgia in April
      2007, and the diagnosis was locally-advanced cancer of pancreatic body (4 cm,
      Stage IVa) in June 2007. Laparotomy was performed, but the locally-advanced
      cancer was unresectable because of the invasion to the celiac trunk and superior
      mesenteric artery. Tumor biopsy and intra-operative radiotherapy (IORT, 12 MeV,
      20 Gy) were only performed. The result of biopsy was moderately-differentiated
      adenocarcinoma. After laparoptomy, systemic chemotherapy (gemcitabine 1,000
      mg/body) was performed once a week. After 4-set chemotherapy, her cancer pain was
      completely relieved and the tumor size was decreased to 25 mm on CT scan in
      October 2007. She has been treated as an outpatient.

PMID- 19106542
TI  - [A case report-advanced pancreas cancer with liver and lung metastases well
      controlled over one year by combination therapy with systemic chemotherapy,
      radiation and hepatic arterial infusion in an outpatient setting].
AB  - We report a case of advanced pancreatic cancer with liver and lung metastases
      that was well controlled over one year by combination therapy with systemic
      chemotherapy, radiation and hepatic arterial infusion in an outpatient setting.
      The patient was a 74-year-old woman. Chief complaints were back pain and
      anorexia. She was diagnosed with pancreas cancer with liver and lung metastases
      at the time of first visit. We started systemic chemotherapy with gemcitabine 1
      g/body and 5-FU 1 g/body alternately every other week on an outpatient basis. At
      1.5 months (M) after initiation of chemotherapy, we started radiation therapy to
      the main tumor at a total dose of 40 Gy. After radiation, chemotherapy was
      resumed. As a result, the size of the main tumor decreased but metastatic liver
      tumors got larger. Then we changed to combination therapy with systemic
      chemotherapy (gemcitabine and 5-FU) and hepatic arterial infusion (5-FU weekly).
      Liver metastases almost disappeared after 7.5 M. Despite all these treatments,
      however, the number of metastatic lung tumors increased. The patient was
      hospitalized for 15 M and died after 17 M. We focused on and succeeded in the
      prolongation of lifetime and maintenance of QOL by combination therapy with
      systemic chemotherapy, radiation and hepatic arterial infusion therapy.

PMID- 19106543
TI  - [S-1+gemcitabine (GEM) therapy was effective in a case of unresectable pancreatic
      head carcinoma].
AB  - OBJECTIVE: Treatment results of pancreatic head carcinoma are not good and long
      term survival, especially in nonresectable cases is extremely difficult to
      obtain. The case reported here is of nonresectable pancreatic head carcinoma in
      which S-1+gemcitabine (GEM) proved to be effective. CASE: A 70-year-old male. The
      patient initially complained of epigastralgia. Jaundice was also noted and upon
      further study, pancreatic head carcinoma, portal vein and common hepatic artery
      infiltration along with duodenal infiltration were diagnosed. Gastrojejunostomy
      and cholecystectomy were performed with a preoperative diagnosis of Phb, TS2
      infiltrative type T4, CH (+), DU (+), S (+), RP (-), PV (+), Ach (+), PLX, OO (
      ), N0, M0, and Stage IVa. Perioperative findings showed no hepatic or peritoneal
      metastases. Following surgery, S-1+ GEM (S-1 100 mg/day, day 1-14; GEM 1,000
      mg/m(2) was administered on day 8 and day 15 for 2 weeks followed by one week of
      no administration) was started. After completing 2 courses, there was no change
      in the tumor, but after finishing the sixth course, there was a notable reduction
      in tumor size, and after finishing the 10th course, a further reduction was
      noted. Currently at the end of the 14th course, the tumors are unidentifiable
      upon imaging. At 1 year and 5 months from the initial diagnosis, there has been
      no recurrence and chemotherapy is being continued. In the case reported here,
      there have been no adverse side-effects from the S-1+GEM therapy, it is a safe
      method which does not lower QOL in patients with unresectable pancreatic
      carcinoma, and we can look forward to the possibility of extended survival times.
      CONCLUSION: In the case of unresectable pancreatic carcinoma, S-1+GEM therapy may
      be able to provide an improved long-term prognosis.

PMID- 19106545
TI  - [A case of liver metastasis of mixed acinar-endocrine carcinoma treated with
      various loco-regional cancer therapies].
AB  - Mixed acinar-endocrine carcinoma of pancreas is a very rare tumor. We report a
      60s female patient with pancreatic mixed acinar-endocrine carcinoma and liver
      metastasis. The patient admitted for further examination of pancreatic head mass.
      Computed tomography scan of abdomen showed a large tumor in pancreatic head and
      liver tumor. Angiography revealed a presence of embolism in portal vein. We
      conducted a pylorus-preserved pancreatoduodenectomy with resection of the portal
      vein on the diagnosis of acinar cell carcinoma by fine needle aspiration biopsy.
      Pathological examination showed a mixed acinar-endocrine carcinoma. Following the
      operation, the liver metastasis was controlled with various loco-regional cancer
      therapies.

PMID- 19106544
TI  - [Effective combination chemotherapy with gemcitabine hydrochloride, S-1 and
      nedaplatin for recurrent pancreatic cancer--a case report].
AB  - A 57-year-old man who had brown urine, jaundice and appetite loss from June 2006
      was diagnosed with advanced pancreatic cancer. He received pylorus-preserving
      pancreatoduodenectomy in July 2006. Liver metastasis in S6 lesion was revealed by
      abdomen CT and SPIO-MRI in November and December 2006, respectively. Chemotherapy
      with gemcitabine hydrochloride (GEM) 1,400 mg/body was administered once a week
      on days 1, 8 and 15 for 4 weeks. At the beginning of this chemotherapy, it seemed
      to be a stable disease, but abdominal CT revealed a tumor progress in April 2007.
      So we selected combination chemotherapy with GEM and S-1 as second-line. At first
      serum CA19-9 was decreased but gradually increased, and the CT scan revealed the
      tumor progression in the liver and the local recurrence appeared in February
      2008. So we selected combination chemotherapy with GEM and nedaplatin as third
      line. After 2 months, CT scan revealed no change in tumor size. This combination
      chemotherapy can be effective in some patients with GEM-refractory pancreatic
      cancer.

PMID- 19106546
TI  - [A case of intraluminal/external irradiation, chemotherapy and T-tube stent
      treatment for the local recurrence of the postoperative four-year bile duct
      cancer].
AB  - The patient was a 73-year-old man. In 2001, PPPD was performed. After
      confirmation of an expanded intrahepatic bile duct and anastomic stenosis in July
      2005, PTBD was performed into the B3. Adenocarcinoma was detected with bile
      cytodiagnosis, and was diagnosed as a recurrence of the left bile-duct
      anastomotic site. Under the informed consent, chemo-radiotherapy was performed in
      addition to beam radiotherapy (30 Gy) in September 2005. Then we performed an
      intracavitary irradiation at 25 Gy. UFT (200 mg) was administered along with the
      radiation therapies. After that, an internal fistularization due to the T-tube
      was done. Liver metastasis was confirmed by abdominal CT in 2006. We started
      administering of GEM (600 mg/body) every other week after the recurrence of the
      bile duct cancer. The patient had survived for 24 months from the recurrence. We
      report a good result of the recurrent bile duct cancer treated with combined
      modality therapy.

PMID- 19106548
TI  - [Multimodal therapy for juvenile advanced rectal carcinoma].
AB  - A 37-year-old male with locally advanced rectal carcinoma and liver metastasis
      was treated by multimodal therapy. Since he had severe anemia and perineal
      abscess, sigmoid colostomy was constructed. After his general condition was
      recovered, the patient received systemic chemotherapy with mFOLFOX6 (6 courses)
      and whole pelvic irradiation (40 Gy). The rectal tumor showed a reduction in
      size, total pelvic evisceration combined with reconstruction of ileal conduit and
      rectus abdominus myocutaneous (RAM) flap were performed. He was followed by 7
      courses of systemic chemotherapy with mFOLFOX6 and bevacizumab. After partial
      hepatic resection, he was followed by systemic chemotherapy with FOLFIRI and
      bevacizumab as an outpatient. Recent studies for outcomes in young colorectal
      carcinoma patients showed that the poor prognosis was not caused by its proper
      aggressiveness in biologic behavior but just the late diagnosis.

PMID- 19106547
TI  - [A case of huge advanced rectal cancer invaded into the surrounding organs
      resected successfully after preoperative chemotherapy with mFOLFOX6].
AB  - In the recent improvement in chemotherapy for advanced rectal cancer, a treatment
      for rectal cancer involving the surrounding organs has been well thought out. In
      this report, we described a case of advanced rectal cancer invaded into the
      surrounding organs was resected successfully after preoperative chemotherapy with
      mFOLFOX6. The case was a 74-year-old man with advanced rectal cancer (type 3). A
      close examination of the patient revealed a bowel movement disturbance. Bowel
      obstruction was treated with transverse colostomy. Then chemotherapy (mFOLFOX6)
      was performed six times. It was judged at first to be a huge tumor of 15 cm in
      diameter, which was unresectable due to invasion into the urinary bladder and
      sacrum. However, after mFOLFOX6 was enforced, the tumor was shrunk to about 5 cm
      in diameter (effect judgment PR). Then the tumor was successfully resected. A
      pathologic histology inspection of the tumor, judged to be Grade 2 prior to
      resection, revealed a differentiation type glandular carcinoma and a highly
      lymphocytic infiltration. These results suggested that an appropriate
      preoperative chemotherapy was useful for huge rectal cancers involving the
      surrounding organs such as urinary bladder and sacrum.

PMID- 19106549
TI  - [Modified FOLFOX6 treatment for obstructive jaundice caused by hepatic lymph-node
      metastasis from liver metastases of rectal cancer--a case report].
AB  - Chemotherapy is potentially hazardous for patients with liver dysfunction.
      Although FOLFOX regimen is one of the standard chemotherapies for nonresectable
      liver metastases of colorectal cancer, the safety of this regimen has not been
      established yet in patients with obstructive jaundice associated with multiple
      liver metastases. We report a case of nonresectable liver metastases of rectal
      cancer treated by modified FOLFOX6 regimen after percutaneous transhepatic
      biliary drainage for obstructive jaundice, which was caused by hepatic lymph-node
      metastasis. Five days after giving a birth, a 32-year-old woman underwent
      Hartmann's procedure for perforation of rectal cancer associated with multiple
      liver metastases. She was admitted again to receive chemotherapy 35 days after
      surgery, but the level of total bilirubin was elevated (3.9 mg/dL). Since the
      total bilirubin level was not rapidly decreased after PTBD, the modified FOLFOX6
      regimen was started with a 70% dose. After an introduction of mFOLFOX6 treatment,
      a biliary-stenting was successfully performed, and the mFOLFOX6 continued with a
      full dose starting from the 5th cycle. Although the therapeutic efficacy after an
      additional 8-cycle was classified as stable disease (SD), she did not show any
      sign of adverse effects except for grade 1 neurotoxicity.

PMID- 19106550
TI  - [A case report of lipoma-like tumor during hepatic arterial infusion
      chemotherapy].
AB  - The patient was a 65-year-old male, who had been performed partial resections of
      the colon (descending colon cancer and rectal cancer: Stage IIIa). Multiple
      hepatic metastases were observed 1 year and 10 months after the operation.
      Hepatic arterial infusion chemotherapy was started, and a complete response for
      liver metastases had been continuing for 2 years. On the seventh month after the
      hepatic arterial infusion chemotherapy was started, a lipoma-like tumor of
      approximately 10 cm was found under the diaphragm on the left side. The tumor was
      suspected to be a lipoma on imaging and it had a tendency for enlargement. Two
      years and two months after hepatic arterial infusion chemotherapy was begun, the
      patient was hospitalized for excision of the tumor. Intraoperative findings
      indicated that there was a 3.5 cm mass in the greater omentum in addition to the
      aforementioned tumor under the left diaphragm. Both masses were excised. The
      histopathological findings showed that the tumor under the left diaphragm was
      composed of adipose tissue with coagulative necrosis. The existing adipose tissue
      was thought to have necroses and had become encapsulated. Similar findings were
      obtained for the mass in the greater omentum. Contrast study using a port system
      revealed stenosis of hepatic artery and defluxion of contrast medium into splenic
      artery and inferior phrenic artery. We speculated that the lipoma-like tumor was
      formed by the angitis with the change of the drug distribution.

PMID- 19106551
TI  - [A case of submucosal invasive cancer of the sigmoid colon, recurring as multiple
      liver metastases one year after the surgery].
AB  - A 55-year-old woman underwent colonoscopy due to a positive fecal occult blood
      test during a mass screening examination, and a 0-Ip type early cancer in the
      sigmoid colon was found. Endoscopic mucosal resection was performed for this
      lesion. Histological examination of the endoscopic resected specimen showed a
      well-differentiated adenocarcinoma invading submucosal layer (depth of invasion,
      6,000 microm), positive lymph vessel invasion, and cut end negative. The patient
      was referred to our hospital, and an additional sigmoidectomy with
      lymphadenectomy was conducted. Histological examination revealed no residual
      cancer and no lymph node metastasis. One year after the surgery, an abdominal CT
      scan showed liver metastases in the segment 4 and 7. The patient underwent a
      medial segmentectomy and partial resection of the segment 7 of the liver. After
      the surgery, 8 courses of oral UFT/LV therapy as adjuvant chemotherapy were
      administered. The patient remains free of recurrence 2 years and 7 months after
      the first surgery.

PMID- 19106552
TI  - [A case report of a patient with hand-foot syndrome induced by bolus 5
      fluorouracil therapy].
AB  - We present a case of hand-foot syndrome (HFS) induced by bolus 5-fluorouracil (5
      FU) therapy. A 54-year-old man received bolus 5-FU for adjuvant treatment of
      rectal cancer. After second cycle, he presented to the clinic with a rash on the
      both palms accompanied by symptoms of pain, erythema, swelling, and desquamation
      consistent with grade 2 HFS. HFS appears more frequently with 5-FU delivered by
      continuous infusion or with the 5-FU oral derivative capecitabine than with bolus
      5-FU therapy. HFS is a leading cause of treatment interruption which may impact
      on the efficacy of the treatment regimen. This possibility must be considered
      when patient is receiving a bolus 5-FU treatment, and effective and appropriate
      patient education is an essential part of management to prevent progression to a
      more severe grade of toxicity by early detection of HFS.

PMID- 19106553
TI  - [A case of recurrent colon cancer patient who gained a long-term survival by
      repeated and aggressive surgical resection].
AB  - A case is a woman of 55-years-old. We performed right hemicolectomy with liver S7
      partial excision (a postoperative diagnosis of the hepatic lesion, adenoma) for
      ascending colon carcinoma of type 2 with hepatic metastasis. Postoperative
      diagnosis was ss, n2, ly2, v2, Stage IIIb, based on the Japanese classification
      of colon cancer. Twelve months after the first operation, she was developed
      intestinal atresia by an abdominal wall recurrence, and we performed the
      operation of abdominal wall mass resection with a partial resection of small
      bowel. Afterwards she developed a recurrence three times in the abdominal wall or
      intra-abdominal lymph nodes during the next 1 year and six months, and we
      performed a local excision each time. The pathological findings in reoperations
      were all metastasis from ascending colon carcinoma of primary operation. After
      the final operation, we did not perform chemotherapy because the patient wished
      not to have it. There has been no recurrence for 6 years since the first
      operation, or 3 years since the last operation. Recently, the therapy for
      recurrent colon cancer has been shifted to more effective chemotherapy such as
      FOLFOX or FOLFIRI regimen, and a surgical resection is becoming rare. However, we
      experienced a case of recurrent colon cancer treated with four aggressive
      surgical resections that was beneficial for a long-term survival.

PMID- 19106554
TI  - [A case of long-term disease free survival after three surgical resections for
      local recurrence and lung metastases from rectal cancer].
AB  - Six years ago, a 67-year-old-man underwent Mile's operation for rectal cancer. He
      complained of lower back pain in 1999, and was diagnosed with local recurrence
      from rectal cancer. The tumor invaded to the bladder, prostate, internal
      obturator muscle, and the piriform muscle. We performed a total pelvic resection
      and systemic chemotherapy with low-dose 5-fluorouracil/cisplatin. Since lung
      metastases were pointed in 2001, he received chemotherapy consisted of irinotecan
      and 5'-DFUR for 1 year, and a partial resection for lung metastasis was performed
      in 2002. After a partial resection for subsequent lung metastasis occurred in
      2003, he has survived more than 5 years. A surgical resection is an effective
      treatment for a localized recurrence from colorectal cancer.

PMID- 19106555
TI  - [CT-guided radiofrequency ablation therapy for pelvic recurrence from rectal
      carcinoma--a case report].
AB  - A 48-year-old man, who had undergone a low anterior resection for advanced lower
      rectal cancer on May 27, 2003, was admitted to our hospital with anastomosis
      recurrence in November 2004. After chemo-radiotherapy (5-FU 250 mg/ body
      continuous infusion, 5 Gy each 5 fragments), an abdomino-perineal resection was
      performed on December 1, 2004. A follow-up CT scan showed pelvic local
      recurrences located dorsal to prostate in January, and the presacral region in
      July 2006. Because of presence of complication of acute promyelocytic leukemia
      (APL), this patient had a poor general condition. So radiofrequency ablation
      (RFA) therapy was performed as a palliative therapy. A presacral relapse was
      revealed in three months after RFA. As a complication, two weeks after RFA for
      the presacral region, a vesicoctaneous fistula occurred, and it required a
      urinary diversion. He died of APL on August 27, 2007. CT-guided radiofrequency
      ablation is useful for pelvic recurrence from rectal cancer of poor-risk patient.

PMID- 19106556
TI  - [A complete response of locally-advanced poorly differentiated adenocarcinoma of
      the rectum to pre-operative chemo-radiation therapy].
AB  - A 71-year-old woman with peri-anal pain and anal bleeding was found to have a
      tumor in lower rectum in colonoscopic examination, which was histologically
      diagnosed as poorly differentiated adenocarcinoma. Computed tomography and
      magnetic resonance imaging showed a tumor 5 cm in diameter deeply infiltrating
      mesorectum, and swelling of intra-pelvic lymph nodes. At the first operation,
      infiltration of the tumor was so deep that a complete surgical resection was
      considered to be difficult, and only a sigmoid colostomy construction was done.
      After chemo-radiation therapy of 50.4 Gy and 5-FU plus levofolinate calcium
      (Isovorin) infusion, the tumor was reduced in size and lymph nodes were extremely
      decreased. The patient underwent an abdominoperinial resection 6 weeks after the
      end of chemo-radiation, and pathological examination revealed a complete
      replacement of tumor with necrosed tissue, and no viable tumor cell was found.
      Poorly differentiated adenocarcinoma of the colon is reported to be highly
      malignant and associated with poor prognosis. Preoperative chemo-radiation
      therapy can be a promising candidate for adjuvant treatment of locally-advanced
      poorly differentiated adenocarcinoma of the rectum.

PMID- 19106557
TI  - [A case of successful treatment with OK-432 administration into lymphatic cyst
      formed after resection of rectal cancer].
AB  - We herein report a case of successful treatment with OK-432 administration into
      lymphatic cyst formed after resection of rectal cancer. A 61-year-old male
      patient underwent a very low anterior resection with D3 lymphadenectomy for
      locally advanced rectal cancer. Four months after the surgery, he arrived at our
      department with lower abdominal fullness. He was diagnosed as having bilateral
      intra-pelvic abscess by CT scan, and underwent a tube-drainage. After drainage,
      abscess lesions were shrunk, but a serous discharge remained. Because we
      diagnosed lymphatic cysts caused by the delayed lymphatic discharge after
      lymphadenectomy, an administration of OK-432 into cysts was performed. After
      administration, the discharge was decreased, and then fistula was closed.

PMID- 19106558
TI  - [A case of multiple lymph node metastases from transverse colon cancer
      successfully treated with oral tegafur/uracil (UFT)/Leucovorin (LV)].
AB  - Oral tegafur/uracil (UFT)/Leucovorin (LV) therapy has been used for chemotherapy
      for advanced colorectal cancer with anti-cancer effects the same as conventional
      5-fluorouracil and Leucovorin (5-FU/LV). However, the effectiveness and safety of
      UFT/LV in the treatment of elderly patients with advanced colorectal cancer is
      not evaluated. We report a case of multiple lymph node metastases from colon
      cancer successfully treated with UFT/LV. An 81-year-old man had been admitted to
      our hospital because of left neck and axillary mass, which was diagnosed as
      transverse colon cancer with multiple lymph node metastases. After a laparoscopic
      partial resection of transverse colon, UFT/LV (UFT 300 mg/m2/day and LV 75
      mg/day) was administered for 4-week-on and 1-week-off. After the administration
      of the chemotherapy, a good partial response of these metastatic lymph nodes was
      achieved. No grade 3 or more severe adverse reactions have been observed. He has
      now survived for 14 months without a recurrence after the administration of the
      chemotherapy. This case suggests the effectiveness and safety of UFT/LV in
      elderly patients with colorectal cancer.

PMID- 19106559
TI  - [A case of advanced sigmoid colon cancer performed resection of liver metastases
      after long-term control by S-1 and CPT-11 combination chemotherapy].
AB  - A 60-year-old man diagnosed as advanced sigmoid colon cancer was performed
      sigmoidectomy and D3 lymph node dissection. Intra-operative findings were SE,
      P0H1N4M (-), and Stage IV. One month after the operation, we started a
      combination chemotherapy using S-1 plus CPT-11 as one course for five weeks. S-1
      (120 mg/body/day) was orally administered continuously for 3 weeks, and CPT-11
      (80 mg/m2) was done intravenously on days 1 and 15. A Follow-up abdominal CT scan
      revealed a drastic reduction of liver metastasis and disappearance of para-aortic
      lymph node swelling (PR in). The combination chemotherapy was once finished after
      eight courses due to the patient's request. However, we started to administer the
      same regimen to him again six months later because of re-growth of liver
      metastasis. An additional six-course administration resulted in a reduction of
      liver metastasis by CT scan, and no other abnormal concentration besides two
      liver metastases by PET-CT examination was observed, and we performed a partial
      resection (two parts) of the liver and cholecystectomy 24 months after the first
      operation. The patient has been alive with disease free for five months since the
      second operation.

PMID- 19106560
TI  - [A case of metastatic liver cancer from rectal cancer demonstrating a clinical CR
      with 3D-CRT].
AB  - The patient was a 62-year-old man who underwent a low anterior resection for
      rectal cancer. The tumor was a moderately differentiated adenocarcinoma, type 2
      in the Japanese classification of colorectal carcinoma. The tumor was considered
      to be in stage I (mp, n (-), P0, H0, M (-)). He did not receive any adjuvant
      chemotherapy. After 6 months from the surgery, ultra sound sonography and an
      abdominal CT scan revealed a 30 mm hepatic nodule lesion. We diagnosed liver
      metastasis of the rectal cancer. The patient refused a surgery and chemotherapy.
      We chose radiotherapy for liver metastasis. He was given a total dose of 60 Gy/10
      fractions/10 days with 3D-CRT. After 1 month from the radiotherapy, the tumor was
      reduced to 17 mm in size and regressed gradually. At 19 months from the radio
      therapy, the disease was diagnosed as CR because no tumors were detected. There
      has been no recurrence for 25 months since his irradiation. 3D-CRT appears to be
      effective for liver metastasis from the rectal cancer.

PMID- 19106561
TI  - [Radio-frequency ablation therapy to the liver metastasis from colon cancer which
      neighbors a hepatic-cyst].
AB  - We report a case of liver metastasis from colon cancer successfully treated with
      radio-frequency ablation therapy. The patient was a 75-year-old man. We performed
      sigmoidectomy in February 2006, but a metastatic-focus in S5 segment of the liver
      with the size of 28 mm was discovered by November 2006. Chemotherapy was enforced
      to the patient but we could not control the metastasis. There were multiple
      hepatic-cysts in his liver and one with size of 60 mm surrounded the metastatic
      focus. RFA therapy was performed after enforcing a percutaneous ethanol
      sclerosing therapy to the neighboring hepatic-cyst. After 4 months from RFA
      therapy, the CT showed a good cauterization effect on the metastasis. We thought
      that RFA therapy after enforcing a percutaneous ethanol sclerosing therapy to the
      neighboring hepatic-cyst was as good as hepatectomy with low invasiveness.

PMID- 19106562
TI  - [Complete response of advanced rectal cancer with combined therapy of S-1 + chemo
      radiation plus FOLFIRI--a case report].
AB  - A 64-year-old man was admitted to general practitioner because of dyschezia. He
      was diagnosed with lower rectal cancer by colonoscopy and referred to our
      hospital for therapy. At first, in spite of multiple liver metastases, we tried a
      resection of primary lesion in order to control of breeding, dyschezia and pain.
      However, we had to give up the resection, so we made sigmoid colostomy only. One
      month after the operation, a combination chemo-radiotherapy using S-1 was
      performed for controlling of local symptom. S-1 (120 mg/day) was administered on
      days 1-14, and 21-35. Radiation (2 Gy) was administered on days 1-5, 7-12, 14-19,
      21-26, 28-33, and 35-40, a total of 60 Gy. One month after this therapy, the
      tumor was remarkably reduced and the reduction was judged as partial response.
      Moreover after 6 courses of FOLFIRI, the reduction was judged as complete
      response. Local control therapy (S-1+chemo-radiation) plus systemic therapy
      (FOLFIRI) is one of the promising effective therapies for advanced rectal cancer.

PMID- 19106564
TI  - [Hepatic lymph-node involvement in patients with synchronous liver metastasis
      from colorectal cancer-a correlation with the grading system for liver
      metastasis].
AB  - This retrospective study was performed to clarify the frequency and clinical
      significance of hepatic lymph-node metastasis in patients with synchronous liver
      metastasis from colorectal cancer, in relation to the grading system of liver
      metastasis classified by the 7th Edition of General Rules for Clinical and
      Pathological Studies on Cancer of the Colon, Rectum and Anus. Hepatic lymph-node
      metastasis was histologically examined in 61 patients with synchronous liver
      metastasis whose primary lesion was resected. The incidence of hepatic lymph-node
      metastasis for all patients was 26%. The frequency was 8% in Grade A (n=13), 20%
      in Grade B (n=15), and 36% in Grade C (n=33) (p=0.09). Among patients classified
      in Grade A/Grade B, the patients with hepatic lymph-node metastasis showed a
      shorter survival time than those without metastasis (p<0.01). Among patients in
      Grade C, there was no significant difference in survival times between the
      patients with hepatic lymph-node metastasis and those without metastasis
      (p=0.59). In conclusion, the incidence of hepatic lymph-node metastasis should be
      considered regardless of the Grade of liver metastasis from colorectal cancer.

PMID- 19106563
TI  - [A case report of complete remission of relapsed rectal cancer liver metastasis
      after systemic chemotherapy successfully treated by radiofrequency ablation].
AB  - We report a case of complete remission of relapsed rectal cancer liver metastasis
      after systemic chemotherapy successfully treated by radiofrequency ablation
      (RFA). A 60-year-old man was diagnosed as having rectal cancer with colonoscopy
      and as solitary liver metastasis with enhanced CT. After primary tumor was
      resected, modified FOLFOX6 chemotherapy was performed. A complete response (CR)
      was observed after the eighth course, and the chemotherapy was finished at the
      twelfth course. Recurrence of liver metastasis was showed after the chemotherapy
      for six months, so RFA was performed without any complications. He is living
      without relapsing for eight months. We basically performed first was systemic
      chemotherapy to liver metastasis of colorectal cancer, and performed a local
      treatment including resection, if necessary. We suppose that RFA after systemic
      chemotherapy is one of the useful treatment strategies for liver metastasis of
      colorectal cancer, because RFA is less invasive than resection and a
      discontinuation of the drug is not required for RFA.

PMID- 19106565
TI  - [Prognosis of patients undergoing resection of both hepatic and pulmonary
      metastases from colorectal cancer].
AB  - This retrospective study evaluated the prognosis of patients undergoing resection
      of both hepatic and pulmonary metastases from colorectal cancer. The subjects
      were 14 patients who underwent resection of both hepatic and pulmonary metastases
      from colorectal cancer between January 1991 and January 2008. The range of
      patient age at first metastatectomy was 48- 73-years-old (median 59). The ratio
      of males to females was 4 to 3. Hepatic metastatectomy proceeded to pulmonary
      metastatectomy in 10 cases, while pulmonary metastatectomy was performed first in
      4 cases. The median duration of relapse-free survival and overall survival after
      the second metastatectomy was 11.2 months and 20.4 months, respectively. The
      overall survival after the second metastatectomy tended to correlate with the
      relapse-free survival after the first metastatectomy (rs=0.55, p=0.08). In
      conclusion, relapse-free survival after the first metastatectomy should be
      considered when a second metastatectomy is scheduled in patients with both
      hepatic and pulmonary metastases from colorectal cancer.

PMID- 19106566
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 21
      patients with synchronous liver metastases from colorectal cancer for the last
      ten years to investigate the usefulness of HAIC for those patients. In 7 cases
      with resection of liver metastases, the median survival time (MST) was 49 months,
      mean survival time was 56.3 months and a 5-year survival rate was 43%. In 14
      cases without resection of liver metastases, 2 cases had complete response (CR),
      8 cases had partial response (PR), 4 cases had stable disease (SD), and the
      response rate was 71%. There was a significant difference in the survival time of
      each response. MST was 27 months, and mean survival time was 38.5 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- 19106567
TI  - [Hepatic artery infusion chemotherapy to three liver metastasis cases in which
      systemic chemotherapy was impossible or ineffective].
AB  - Recently, standard therapies for either gastric cancer or colorectal cancer have
      been established through the development of multidrug systemic chemotherapy and
      the appearance of molecular targeting drugs. For example, either FOLFIRI or
      FOLFOX therapy is normally chosen for the treatment of unresectable liver
      metastasis from colorectal cancer. On the other hand, hepatic artery infusion
      (HAI) chemotherapy is generally used as only a second-line therapy. There are,
      however, some cases in which systemic chemotherapy is not indicated due to age
      and/or the risk of side effects. We herein report three cases that were treated
      by HAI after initially performing systemic chemotherapy in order to treat liver
      metastasis from either gastric cancer or colorectal cancer.

PMID- 19106568
TI  - [Expandable metallic stent treatment for obstructive colorectal cancer patients].
AB  - The expandable metallic stent (EMS) have been used to treat obstructive
      colorectal cancer. We used EMS in 13 out of 14 cases of obstructive colorectal
      carcinoma patients (insertion rate 93%). Of these 13 cases, 6 cases were male
      patients, and 7 cases were female patients. The average age was 69.1-years-old
      (44-87). The placement of insertion part in rectum and sigmoid colon was 8 cases
      and 5 cases, respectively. We detained Ultraflex non-covered type for all
      patients. Seven patients were able to have an operation after stenting. After the
      stent treatment, 11 patients were able to eat, and 7 patients were discharged
      from hospital. COMPLICATIONS: perforation and stent migration were occurred in
      one case. These results suggested that EMS might be an effective treatment for
      obstructive colorectal carcinoma.

PMID- 19106569
TI  - [Problems involved in the resection of pulmonary metastasis from colorectal
      cancer in the era of new anticancer drugs].
AB  - BACKGROUND AND PURPOSE: Surgical resection has been the standard treatment
      recommended for respectable pulmonary metastasis from colorectal cancer. However,
      we should evaluate again the indication of bilateral thoracotomy and repeat
      resection of pulmonary metastatic lesions, because these surgical interventions
      may deteriorate the patients' quality of life. This retrospective study was
      performed to address this issue. PATIENTS AND METHODS: The subjects were 39
      patients who underwent pulmonary metastatectomy of colorectal cancer between May
      1990 and January 2007. The prognosis was evaluated according to the types of
      thoracotomy, bilateral thoracotomy (n=5), repeat pulmonectomy (n=6), and single
      thoracotomy (n=28). In addition, the impact of new anticancer drugs (5
      fluorouracil+Leucovorin, S-1, irinotecan, and oxaliplatin) on survival after
      thoracotomy was examined. RESULTS: The patients undergoing bilateral thoracotomy
      showed a significantly shorter survival after the last thoracotomy than those in
      other groups (p=0.03). The survival time after the initial thoracotomy was not
      different between patients who received new anticancer drugs (n=11) and those
      without (n=28, p=0.58). CONCLUSIONS: Bilateral pulmonary metastatectomy from
      colorectal cancer appears to have little benefit on survival, while a repeat
      metastatectomy may cause a long-term survival. A further collection of cases is
      needed to conclude whether the new anticancer drugs would be useful for
      prolonging the patients' survival after pulmonary metastatectomy.

PMID- 19106570
TI  - [Surgical resection of pulmonary metastases from colorectal carcinoma in our
      hospital].
AB  - Pulmonary metastases from colorectal carcinoma are not rare next to liver
      metastases. Lung resection has been widely accepted, but postoperatively local
      lung recurrence has been seen in the wedge resection procedures. In our hospital,
      specimen of the wedge resection was histologically reviewed and revealed floating
      cancer cell clusters around the main tumor. The cause of the recurrence was
      supposed to be floating clusters or a technical problem of surgical margin in the
      video-associated thoracic surgery. Since 2004, we used 3-dimensional CT and
      identified the pulmonary segmental area of peripheral metastatic tumor less than
      2.0 cm in diameter. From 1986 to 2003, we performed 18 cases of lung resection
      and found that recurrent cases were 25 to 64%. On the other hand, we detected 0
      to 16% recurrence cases in 12 patients during the period of 2004-2007. We
      recommend segmentectomy to metastatic tumor less than 2.0 cm in diameter from
      colorectal carcinoma.

PMID- 19106571
TI  - [Radiofrequency ablation of malignant lung tumors--preliminary report of 12
      cases].
AB  - Percutaneous CT fluoroscopy-guided radiofrequency ablation (RFA) was performed in
      12 patients with 4 primary and 8 metastatic lung cancers as a pilot study. The
      main complication was a pneumothorax, which occurred in six cases and 2 of them
      required a chest tube drainage. Four patients died of extrapulmonary tumor
      progression at 3-17 months after RFA. The remaining 8 patients were alive with
      the disease and their median follow-up period was 12 months (range, 6-39 months).
      An overall survival rate was 75% at 6 months, 63% at 1 year and 43% at 2 years. A
      local progression occurred in 4 cases at 4-17 months after RFA and the cause of
      relapse was considered as insufficient ablation due to tumor localization close
      to the trachea, SVC or intrapulmonary vessels and bronchi. A local control rate
      was 92% at 6 months, 64% at 1 year and 35% at 2 years. CONCLUSION: RFA of lung
      tumors is a safe and minimally invasive therapeutic intervention with a good
      local control for sufficiently ablated lesions. So it appears to be a favorable
      treatment option for high-risk patients or those with multiple lesions.

PMID- 19106572
TI  - [A case of successfully repeated resections of pulmonary metastasis after
      hepatectomy of hepatocellular carcinoma].
AB  - A 73-year-old woman was diagnosed with solitary hepatocellular carcinoma (18 cm
      in diameter) in the right lobe. Right hepatic lobectomy was performed in March
      2004. Solitary pulmonary metastasis in the left lung was detected by CT scan in
      April 2006. Thoracoscopic resection of pulmonary metastasis was performed. But in
      February 2007, solitary pulmonary metastasis in the right lung was detected by CT
      again. Second thoracoscopic pulmonary resection was performed. Fifty-one months
      after the initial surgery, she is alive without recurrence in the lung. In
      patients with pulmonary metastasis of hepatocellular carcinoma, if recurrence in
      the remnant liver is well controlled and pulmonary metastasis is completely
      resectable, repeated resections of pulmonary metastasis can be an effective
      treatment and improve survival.

PMID- 19106573
TI  - [A complete response (CR) case of multiple lung metastases after radical
      lobectomy for non-small-cell-lung cancer obtained by cisplatin+vindesine].
AB  - A 69-year-old man was diagnosed with squamous cell carcinoma of the lung, and
      underwent right upper lobectomy in October 2000. Histological findings were as
      follows: 2.5 cm in diameter, moderately differentiated squamous cell carcinoma of
      the lung, ly0, v0, n0, pT1N0M0, stage IA. No adjuvant therapies were performed.
      Multiple lung metastases were detected on CT scan in June 2001, and four cycles
      of chemotherapy with cisplatin+vindesine (day 1: cisplatin 100 mg/body, days 1, 8
      and 15: vindesine 3 mg/body) were performed. The metastases were completely
      disappeared on CT scan in December 2001. No relapse has been seen for six years
      and two months.

PMID- 19106574
TI  - [A case of malignant lymphoma that seemed to be thyroid cancer lymph nodes
      recurrence].
AB  - After thyroid cancer was resected, we quite often tend to think of cervical
      lymphadenopathy when metastases to lymph nodes were confirmed. We report our
      experience with a case of malignant lymphoma when we thought it to be for thyroid
      carcinoma recurrence cervical part metastases to lymph nodes. The patient is a 59
      year-old woman. Right lobe resection and lymphadenectomy were done to the patient
      with thyroid carcinoma in 1994. A tumor in the survival thyroid gland was
      confirmed in 1995. Aspiration biopsy cytology was class IIIa. In February 2007,
      the tumor of the survival thyroid gland was enlarged. Echography showed a shape
      irregularity of the tumor. Meanwhile, bilateral cervical part lymphadectomy also
      confirmed. We concluded it to be thyroid carcinoma recurrent cervical metastases
      to lymph nodes and performed a survival total thyroietectomy and a cervical part
      lymphadetectomy. Histopathology diagnosis showed it to be of a papillary
      adenocarcinoma of thyroid recurrence. However, there was no metastasis image of
      the thyroid carcinoma at the cervical lymph node. The diagnosis was malignant
      lymphoma. CONCLUSION: As abrupt cervical lymphadenopathy was confirmed in the
      thyroid recurrence case, it is important to think of lymphatic disorder instead
      of metastasis of thyroid cancer.

PMID- 19106575
TI  - [The efficacy of surgical resection and chemo-endocrine therapy for patients with
      local recurrence or axillary lymph node metastasis of breast cancer].
AB  - We evaluated a surgical resection and chemo-endocrine therapy and prognosis for
      patients with local recurrence or axillary lymph node metastasis of breast
      cancer. Twenty-one patients with local recurrence or axillary lymph node
      metastasis without a distant metastasis were enrolled in this study. Thirteen of
      the 21 patients underwent a surgical resection. Resection of recurrent lesion in
      residual breast after breast conserving therapy for six of the 13 patients,
      axillary lymph node dissection (ALND) for four, and resection of thoracic wall
      lesion for three were performed. Five of the patients who underwent resection of
      residual breast lesion, four of the patients who underwent ALND and two of the
      patients who underwent resection of thoracic wall lesion have survived. One of
      the patients who underwent resection of residual breast lesion and one of the
      patients who underwent resection of thoracic wall lesion were dead. In eight non
      operable patients, five were dead and three have survived. Median recurrence free
      interval was 24 months in operable patients and 27 months in non-operable
      patients. Median survival time after recurrence was 29 months in operable
      patients and 12 months in non-operable patients. The surgical with chemo
      endocrine therapy promises to control well to local recurrence or axillary lymph
      node metastasis for the patients we selected.

PMID- 19106576
TI  - [A case of advanced breast cancer 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 toremifene
      and paclitaxel therapy. The patient was a 38-year-old woman with slight anemia
      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 progesteron receptor, and negative for HER2/neu protein expression.
      She received 6 cycles of tri-weekly FEC (C: 500 mg, E: 60 mg, F: 500 mg/m2) and
      16 cycles of weekly paclitaxel (80 mg/m2) with toremifene (120 mg/day). The
      anemia and the bleeding from the tumor disappeared after FEC chemotherapy. The
      response for breast tumor after paclitaxel and toremifene therapy was evaluated
      as partial response, and the infraclavicular, subpectoral, and interpectoral
      lymph nodes metastasis disappeared. Muscle-preserving radical mastectomy (Bt +
      Ax: Auchincloss) with skin transplantation was performed. She had no recurrence
      during one year after the operation. Paclitaxel and Toremifene therapy was
      effective for advanced breast tumor, and can improve a patient QOL and the
      clinical outcomes in Stage IIIC advanced breast cancer.

PMID- 19106577
TI  - [Recurrence of skin and lymph nodes from asynchronous breast cancer successfully
      treated with paclitaxel and toremifene therapy--a case report].
AB  - We report a case of recurrence of skin and lymph nodes from asynchronous breast
      cancer achieving a significant improvement of QOL by toremifene and paclitaxel
      therapy. The patient was a 49-year-old woman who received both sides of muscle
      preserving radical mastectomy (Bt+Ax: Auchincloss) had a skin redness of her left
      breast. Aspiration biopsy cytology for the skin led to a diagnosis of Class V.
      Skin biopsy for the part of the redness was performed. The pathological diagnosis
      was an invasive ductal carcinoma, negative for estrogen receptor and positive for
      progesteron receptor, and negative for HER2/neu protein expression.
      Ultrasonography showed the subpectral and the inflaclavicular lymph nodes
      swelling and the skin metastasis. Enhancement CT showed no metastasis of brain,
      lung, liver, and other organs. Although she had already received 6 cycles of tri
      weekly FEC (C: 500 mg, E 60 mg, F: 500 mg/m2) after previous operation, we
      performed 7 cycles of weekly paclitaxel (80 mg/m2) with toremifene (120 mg/day).
      The response for the lesion of lymph nodes metastasis after paclitaxel and
      toremifene therapy was evaluated as a complete response. The subpectoral and the
      inflaclavicular lymph nodes metastasis disappeared. However, the skin redness of
      her left breast was still remained. She had received a radiation therapy (30 Gy)
      for skin metastasis. After radiation therapy, we performed a skin biopsy for the
      part of the redness. The pathological diagnosis was no carcinoma of skin. She had
      no recurrence during the two years after the treatment. Paclitaxel and toremifene
      therapy was effective for a recurrent breast tumor and could improve patient's
      QOL and the clinical outcomes.

PMID- 19106578
TI  - [A case of malignant fibrous histiocytoma (MFH) which produced breast cancer
      after an operation].
AB  - The case reported here was a 40-year-old woman. She came to our hospital because
      we palpated on her left breast to locate a tumor. The clinical history showed a
      breast flabellate resection and lymphadenectomy for carcinoma of the left breast
      in 2000. The tumor was scirrhous type, and the histopathology diagnosis showed it
      to be T2N0M0 stage IIA, and the hormone receptor was ER (-), PgR (-). As an
      outpatient, we performed radiotherapy. In 2006, we confirmed a tumor on the right
      side under the left breast wounded area. We left the tumor without a treatment.
      However, the tumor had a tendency to grow in size and was Class V in aspiration
      biopsy cytology, and was diagnosed of sarcoma by needle biopsy. The patient was
      hospitalized in order to have a surgery. We performed a pectoralis muscle merger
      mastectomy and a chest wall restoration by latissimus dorsi muscle dermal flap in
      March 2007. Histopathology diagnosis revealed it to be malignant fibrous
      histiocytoma (MFH). At present, the patient has been treated as an outpatient.
      There has been neither recurrence nor a metastasis with the patient. The patient
      has recently been treated with radiotherapy for the remaining breast after a
      breast preservation surgery. We reported our case with a possibility of MFH
      occurrence in addition to some article considerations.

PMID- 19106579
TI  - [A case of stage IV breast cancer in which a long-term no change state (NC) was
      attained by a combination of S-1 and TAM following AC-T as a primary systemic
      therapy (PST)].
AB  - We here describe a case of advanced breast cancer (Stage IV) in which an oral S
      1+TAM therapy following a primary systemic chemo-radiotherapy has been effective
      in maintaining the patient's QOL. A 40-year-old woman visited our hospital
      because of her left breast tumor. On physical examination, the tumor had invaded
      to the skin adjacent to the nipple forming a skin ulcer and marked deformity of
      the entire breast. Also noted were swollen lymph nodes in the left armpit.
      Subsequently, radiographic imaging tests revealed that the tumor had metastasized
      to the liver and lungs, as well as the skull. Accordingly, a primary systemic
      chemotherapy (4 series of AC/T) was started and followed by local radiation
      therapy (60 Gys) immediately after completing the chemotherapy. The metastasizing
      lesions in the liver, lungs, and skull had markedly reduced in the size and
      number, and the skin ulceration had healed up by these treatments. Afterwards,
      she has been given TAM daily and S-1 for 4 weeks with a 2-week interval. She has
      been quite well without any adverse effects by S-1 and TAM, and the primary as
      well as metastasizing lesions remain stable with normalized tumor marker levels
      (NC) for nearly 3 years.

PMID- 19106580
TI  - [A case of successfully treated orbital metastasis from breast cancer by
      radiation therapy].
AB  - Orbital metastasis from breast cancer is relatively rare. We report a case of
      successfully treated orbital metastasis from breast cancer by radiation therapy.
      This 50-year-old female patient underwent a mastectomy (Bt+Ax) of her left breast
      in October 2000. The diagnosis was invasive lobular carcinoma, Stage IIB
      (T2N1M0). Retroperitoneal and bladder metastases were found five years after the
      operation, and chemohormonal therapy was done. Right orbital swelling appeared 8
      months after chemohormonal therapy, and orbital metastasis from breast cancer was
      diagnosed by MRI. Radiation therapy (a total 30 Gy) was administrated, and the
      swelling disappeared. An MRI was performed 16 months after radiation therapy and
      did not detect any metastases. A complete response (CR) was achieved. No sign of
      recurrence was found, and a sufficient local control has remained for 2 years
      after radiation therapy.

PMID- 19106581
TI  - [A long-term survival case of metastatic breast cancer treated with trastuzumab
      and paclitaxel].
AB  - We report a long-term survival case of metastatic breast cancer treated with
      trastuzumab and paclitaxel. The patient was a 50-year-old female. She underwent
      left mastectomy with axillary lymphadenectomy for advanced breast cancer with
      liver metastases. Histological examination showed papillotublar carcinoma, f, T3,
      ly3, v2, N2 (24/34), histological grade III, ER (-), PgR (-), HER2 (3+).
      Trastuzumab and paclitaxel was performed. One year after the operation, any
      lesions of liver were not detected by CT and she was diagnosed as a complete
      response. No evidence of viable lesions has been found for 7 years. Breast cancer
      with liver metastases often could be a life threatening, and therefore an optimal
      chemotherapy should be applied as soon as possible. Trastuzumab and paclitaxel
      would be one of the optimal chemotherapies for HER2 positive breast cancer.

PMID- 19106582
TI  - [A case of ovarian cancer in which a remarkable effect was seen with
      intrathoracic administration of CDDP and CPT-11].
AB  - A-58-year-old female admitted to our hospital for abdominal fullness and dyspnea
      was diagnosed with malignant pleuro-peritonitis of advanced ovarian cancer. CT
      showed a massive right-sided pleural effusion, massive ascites, and large ovarian
      tumor (about 10 x 15 cm). The patient was treated with intrathoracic
      administration of CDDP and CPT-11. Combination chemotherapy of CDDP (10 mg/week)
      and CPT-11 (10 mg/week) was administered by intrapleural injection every other
      week. As a result (total amount; CDDP 310 mg, CPT-11 250 mg, in 9 months),
      pleural effusion and ascites disappeared. Moreover, marked shrinkage (about 3 x 4
      cm) of the tumor was confirmed. This intrathoracic administration of CDDP and CPT
      11 may be an effective loco-regional therapy for advanced ovarian cancer with
      malignant pleuro-peritonitis.

PMID- 19106583
TI  - [Clinical trial of non-specific immunotherapy using Lentinan in advanced or
      recurrent gastric cancer].
AB  - Randomized phase III study of S-1 alone versus S-1 plus Lentinan (LNT) in
      advanced or recurrent gastric cancer started in February 2007 conducted by the
      Japanese Foundation for Multidisciplinary Treatment of Cancer. The objective of
      this study is to evaluate the superiority of S-1/LNT to S-1 alone. The primary
      end point is to compare over all survival between both treatment groups.
      Secondary end points include time to treatment failure, the grade and rate of the
      adverse events, the evaluation of quality of life (QOL), response rate evaluated
      by RECIST and immunological parameters. QOL is evaluated by Japanese version of
      FACT-BRM questionnaire. Immunological parameters include serum complements (CH50,
      C3) and beta-1, 3 binding monocytes. The sample size is estimated at 150 patients
      per arm. Registration period is 2 years with 2-year follow-up. This study has a
      chance to prove the efficacy of the non-specific biological response modifier. We
      will have to cooperate in order to make this study a success.

PMID- 19106584
TI  - [Hyperthermic immuno-cellular therapy-basic and clinical study].
AB  - BASIC: We treated mice inoculated LLC tumors with hyperthermia or activated
      lymphocytes. Both of hyperthermia and activated lymphocytes therapy reduced not
      only a tumor growth but also lung metastasis. And a combination therapy of
      hyperthermia and activated lymphocytes therapy reduced more of the tumor growth
      and lung metastasis synergistically. CLINICAL: We proceeded with hyperthermia
      (HT) for 472 cancer patients and activated lymphocytes (CAT) therapy for 384
      patients and dendritic cell (DC) therapy for 94 patients. Two-hundred-thirty
      eight patients of them underwent a combination therapy with hyperthermia and CAT
      therapy. And 92 patients received a combination therapy with hyperthermia and DC
      therapy. We proceeded with hyperthermia or immunotherapy for 526 cancer patients.
      And we have 67 clinical benefit cases including 8 complete response (CR) cases.
      These basic and clinical results indicate an effectiveness of a combination
      therapy with hyperthermia and cellular-immunotherapy for cancer patients.

PMID- 19106585
TI  - [Expression of toll-like receptor 4 in colorectal cancer].
AB  - Toll-like receptors (TLRs) play an essential role in innate immunity by
      recognizing various pathogens and by activating acquired immunity. Based on the
      hypothesis that abnormalities of innate immune responses are involved in
      carcinogenesis, we examined the presence or absence of the expression of Toll
      like receptor 4 (TLR4), comprising one of the TLR families, in colorectal cancer
      tissues. TLR4 expression in cancerous and non-cancerous colorectal tissue
      specimens obtained at surgery was investigated by reverse-transcription
      polymerase chain reaction (RT-PCR). Then, TLR4 expression levels were quantified
      by real-time PCR and compared between the 2 groups. TLR4 expression was
      significantly higher in non-cancerous tissues than in cancerous tissues.
      Interestingly, these results suggested that TLR4 expression was up-regulated in
      non-cancerous tissues or down-regulated in cancerous tissues in patients with
      colorectal cancer.

PMID- 19106586
TI  - [Cancer stromal cells influence on the tumor angiogenic pattern].
AB  - Since the progression and metastasis of solid tumors depend on their local
      microcirculation, we sought to characterize the tumor angiogenesis three
      dimensionally in a highly metastatic mouse melanoma model, B16BL6 melanoma
      injected with Matrigel into syngeneic C57BL/6 mice by using confocal laser
      scanning microscopy and transmission electron microscopy. We found that B16
      melanoma within Matrigel grew significantly quicker than B16 melanoma alone and
      was accompanied by altered tumor angiogenesis and avascular area. We
      characterized the unique patterns of avascular area by using confocal laser
      scanning microscopy and transmission electron microscopy.

PMID- 19106588
TI  - [A prediction of prognosis by A-L score in patients with stage IV colorectal
      cancer].
AB  - We analyzed the relationship between A-L score classified by serum albumin level
      and lymphocytes/white blood cells ratio and clinicopathological features in
      patients with Stage IV colorectal cancer. Seventy-nine patients were classified
      by the A-L score. In lower-scored cases, the populations of elderly patients,
      patients with emergency operation and patients with poorer PS were increased.
      Additionally, the 2-year survival rate was decreased as low as A-L score. In the
      multivariate analysis, the A-L score was independent prognostic factor in Stage
      IV colorectal cancer.

PMID- 19106587
TI  - [The significance of Onodera's prognostic nutritional index for the treatment of
      gastrointestinal cancer].
AB  - BACKGROUND: We evaluated the role of the prognostic nutritional index reported by
      Onodera (Onodera's PNI) in patients with gastrointestinal cancer regarding the
      occurrence of postoperative complications. METHOD: Subjects were 324 patients (42
      with esophageal cancer, 107 with gastric cancer, and 175 with colon cancer). We
      classified them into the high risk group (< or = 40) and the non-high risk group
      (> 40) according to Onodera's PNI. We evaluated the rate of the occurrence of
      postoperative complications between the high risk group and the non-high risk
      group. RESULT: The rate of postoperative complications occurring in the high risk
      group was higher than that of the non-high risk group (p=0.04). CONCLUSION:
      Onodera's PNI is useful for patients with gastrointestinal cancer regarding the
      occurrence of postoperative complications.

PMID- 19106589
TI  - [The analysis of CCR4+/CXCR3+ cell ratio in gastrointestinal cancer patients
      receiving chemotherapy or immunotherapy].
AB  - We investigated the expression of CCR4 and CXCR3 with the peripheral blood
      lymphocytes in 31 gastrointestinal cancer patients who received either
      chemotherapy or immunotherapy. The expressions of CXCR3 were 6.8% in the patients
      received chemotherapy and 24.2% in the patients received immunotherapy. The
      expressions of CCR4 were 25.6% in the patients received chemotherapy and 15.4% in
      the patients received immunotherapy. The ratio of CCR4+/CXCR3+ cells was 4.45 in
      chemotherapy and 0.72 in immunotherapy. These results suggested that it was the
      Th2 dominant condition in the patients received chemotherapy and the Th1 dominant
      condition in the patients received immunotherapy.

PMID- 19106590
TI  - [Efficacy of activated lymphocytes transfer therapy as a novel maker for serum
      granulysin level with advanced gastric cancer patients].
AB  - INTRODUCTION: Granulysin is a cytotoxic granule protein of cytotoxic T
      lymphocytes and natural killer cells. Gastric cancer patients of stage II and
      stage III were reported to have pre-operative serum granulysin, which is a good
      prognostic factor. Activated T lymphocytes produce a lot of granulysin in the
      cell. We hypothesized that activated T lymphocytes transfer therapy may increase
      in serum granulysin leveles of stage IV and relapsed patients. METHOD: Between
      April 2002 and December 2007, the patients received a standard therapy with
      activated lymphocytes transfer therapy. Peripheral blood samples were taken from
      the patients. Serum granulysin concentrations were measured using a granulysin
      specific ELISA kit. RESULT: The average serum granulysin level for Stage IV
      (n=29) and relapsed patients (n=13) was 3.3 ng/mL. The gastric cancer patients
      were classified into two groups based on their concentration of serum granulysin
      level: high group (> or = 3.3 ng/mL); low group (< 3.3 ng/mL). There were no
      significant differences between these two groups in gender and age. The stage IV
      high group had a longer survival time than the stage IV low group. After 60 days
      from the activated T lymphocytes transfer therapy, the average pre-treatment
      serum granulysin had increased. However, there was no significant difference to
      note. It is noteworthy that serum granulysin is a novel parameter of patients
      cancer immunity.

PMID- 19106591
TI  - [Indoleamine 2,3-dioxygenase expression in breast cancer patients during
      chemotherapy].
AB  - We evaluated the significance of indoleamine 2,3-dioxygenase (IDO) in recurrent
      breast cancer patients 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 Trp/Kyn ratio
      and immunosuppressive acidic protein (IAP) value in pre-chemotherapies or post
      chemotherapies were studied. There were no correlations between pre-chemotherapy
      and post-chemotherapy in IAP values and Trp/Kyn ratio with weekly paclitaxel
      therapy. And there were no correlations between pre-chemotherapy and post
      chemotherapy in IAP values, but Trp/Kyn ratio in post-chemotherapy was higher
      than re-chemotherapy with tri-weekly docetaxel therapy. These results suggest
      that the weekly paclitaxel therapy may be less invasive for recurrent breast
      cancer patients than the tri-weekly docetaxel therapy.

PMID- 19106592
TI  - [Phase I study of combination therapy with peptide vaccine and anti-cancer drug
      for colorectal cancer].
AB  - Phase I study of combination therapy with peptide vaccine and anti-cancer drug
      for colorectal cancer has been performed in our hospital. The purpose of this
      study was to evaluate the safety and immune response of different dose of RNF43
      721 emulsified with Montanide ISA 51 in combination with S-1/CPT-11 chemotherapy.
      The study design was a dose escalation of peptide (0.5, 1.0, 3.0 mg) with three
      patients' cohort. Nine patients were enrolled. All patients were treated with
      peptide subcutaneously every week and two courses with S-1/CPT-11 chemotherapy.
      Vaccinations were well tolerated without any major adverse events. Immunological
      reactions are not analyzed yet. We herein report a case who has been evaluated to
      be long SD with this intervention for para-aortic LN metastasis from sigmoid
      colon cancer.

PMID- 19106594
TI  - [A clinical experience in treatment with bevacizumab for unresectable colorectal
      cancer].
AB  - Bevacizumab, a humanized monoclonal antibody to VEGF for advanced recurrent
      colorectal cancer, has been known for complications of gastrointestinal
      perforation, hemorrhage, thromboembolism and proteinuria, as adverse effects.
      These findings must be taken care as well as adverse drug reactions (ADR) caused
      by combination chemotherapy. We here in present a clinical experience in
      treatment with bevacizumab for unresectable colorectal cancer. Six patients
      treated with bevacizumab for over two courses until April 2008 were analyzed for
      this study. PR was obtained in one case with mFOLFOX6. Even though, grade 3
      neutropenia was observed in only one case with FOLFIRI, the other cases had grade
      2 or less in ADR. In addition, there were no any specific ADRs related with
      bevacizumab, so we concluded that combination chemotherapy for advanced recurrent
      colorectal cancer with bevacizumab was well-tolerated.

PMID- 19106593
TI  - [A phase I study of combination-therapy with gemcitabine and epitope peptides
      derived from human vascular endothelial growth factor receptor for unresectable
      or recurrent pancreas cancer].
AB  - We are performing a phase I clinical trial of combination-therapy with
      gemcitabine and epitope peptide derived from human vascular endothelial growth
      factor receptor (VEGFR) for advanced pancreas cancer. The aim of this study was
      to evaluate the safety, immunological response and tumor response. Six patients
      have been enrolled at present. During the clinical course, no major adverse
      events were observed. Additionally, two out of 6 cases showed a minor shrinkage
      of the tumor. Immunological response has not been analyzed yet. These results
      indicated that a combination-therapy with gemcitabine and epitope peptides
      derived from VEGFR could be tolerable.

PMID- 19106595
TI  - [Central venous catheterization by using ultrasound guidance to patients with
      terminal stage malignant tumors].
AB  - Central venous catheterization with ultrasound guidance was performed on 41
      patients with terminal stage malignant tumors--112 consecutive insertions at our
      hospital. We performed a total of 112 consecutive insertions: 30 with the skin
      marking method and 82 with the real time echo guidance method. Catheter insertion
      was performed to the internal jugular vein in 24, the supra-clavicular approach
      of the subclavian vein in 4, the infra-clavicular approach of the subclavian vein
      in 37 and the femoral vein in 47. The success rate was 85.7% (96/112 insertions),
      and the mean insertion time was 2.2 minutes. The complication rate was 4.5%:
      arterial puncture for 3 insertions, and mal-position for 2 insertions. In this
      examination, it was confirmed that central venous catheterization with ultrasound
      guidance could be performed safely and briefly in such patients.

PMID- 19106596
TI  - [Regulation of perioperative immunological changes following laparotomy--effects
      of PSK on surgical stress].
AB  - Immune responses have been reported to decline following surgical stress, leading
      to an increased susceptibility to infection or to the growth of tumors. We report
      that preoperative treatment with PSK can inhibit the decline of immunocompetence
      during the perioperative period. BALB/c mice were laparotomized, and then the
      abdomens were closed. The concentrations of IL-6 and of IFN-gamma and IL-4 were
      measured. PSK treatment controlled the stress induced elevation. It was lower in
      the group with surgical stress than in the cultures derived from the non-treated
      group. The IFN-gamma concentration in the group with PSK was significantly higher
      than the level in the group with surgical stress alone. The IL-4 concentration
      was significantly lower in the surgical stress group than the control group.
      However, the concentration tended to be higher in the surgical stress + PSK
      treatment group than the group with surgical stress alone. The IFN-gamma/IL-4
      ratio in the group with surgical stress was lower than the ratio in the non
      treated group. The ratio in the group with PSK treatment was significantly higher
      than the ratio in the group with surgical stress alone. These results suggest
      that PSK restores the abnormality of the biological responses induced by surgical
      stress and corrects the reduced Th1/Th2 cytokine balance to a normal level.

PMID- 19106597
TI  - [Administration of polysaccharide K (PSK) for stage III colorectal cancer in
      clinical practice].
AB  - PURPOSE: This retrospective study was performed to evaluate the administration
      and effect of PSK in patients with stage III colorectal cancer in clinical
      practice. PATIENTS AND METHODS: The subjects were 55 patients with stage III
      colorectal cancer who received adjuvant chemotherapy, comprising UFT in 44,
      UFT/calcium folinate (Leucovorin) in 4 and 5-FU/levofolinate calcium (l-LV) in 7,
      between April 2000 and December 2006. The rate of administering PSK, disease-free
      survival time, and overall survival time were evaluated. RESULTS: The rate of
      administering PSK was 82%. There was no significant difference in disease-free
      survival and overall survival between patients who received PSK and those
      without. Among the patients in stage IIIa, the patients who received PSK tended
      to show a longer overall survival time than those without PSK (p =0.15).
      CONCLUSIONS: The rate of administering PSK is high in patients with stage III
      colorectal cancer. But further cases would be needed to evaluate the effect of
      PSK with 5-FU-based adjuvant chemotherapy.

PMID- 19106598
TI  - [Efficacy and safety of modified FOLFOX6 regimen in aged patients with
      nonresectable colorectal cancer].
AB  - PURPOSE: This retrospective study was performed to clarify the efficacy and
      safety of FOLFOX regimen in aged patients with nonresectable colorectal cancer.
      PATIENTS AND METHODS: We had 92 patients with nonresectable colorectal cancer
      between December 2005 and March 2008. The rate of introducing modified FOLFOX6
      (mFOLFOX6) regimen was compared among the patients aged 75 years or older (n =
      22, aged group) and those aged 74 years or younger (n = 55, younger group). In
      addition, relative dose intensity (RDI), therapeutic efficacy, and adverse events
      in the patients who were given the regimen, we compared between the groups.
      RESULTS: The rate of introducing the regimen was significantly lower in the aged
      group (36%, n = 8) than in the younger group (79%, n = 55) (p<0.01). The RDI
      tended to be lower in the aged group (68.0% versus 79.9%, p=0.10). There were no
      significant differences in the response rate, disease-control rate, progression
      free survival, and overall survival between the groups. The rate of adverse
      events ( > or = grade 3) was not different between the groups ( 50% versus 51%).
      CONCLUSION: Similar to younger patients the mFOLFOX6 regimen is feasible, safe
      and effective in the selected aged patients, although the dose reduction may be
      needed for such patients.

PMID- 19106599
TI  - [The validity of full administration of 5-fluorouracil, irinotecan, and
      oxaliplatin to unresectable or recurrent colorectal cancer].
AB  - PURPOSE: This retrospective study was performed to evaluate a survival benefit of
      the full administration of 5-fluorouracil (5-FU), irinotecan (CPT-11), and
      oxaliplatin (L-OHP) to patients with unresectable or recurrent colorectal cancer.
      PATIENTS AND METHODS: The subjects are 145 patients with unresectable or
      recurrent colorectal cancer who were given CPT-11 and/or L-OHP in addition to 5
      FU. The overall survival times of these patients were evaluated. RESULTS: The
      median survival time (MST) was significantly longer in patients treated with
      three drugs (n=72) than patients treated with two drugs (n =73) (31.6 months
      versus 18.4 months, p<0.01). When analysis was restricted to patients treated
      with three drugs, there was no significant difference in MST between patients who
      were given L-OHP followed by CPT-11 (n=18) and those treated with these two drugs
      in reverse order (n=54) (p=0.67). CONCLUSIONS: Compared with the use of 5-FU in
      combination with CPT-11 or L-OHP, a full administration of three drugs may have a
      more beneficial impact on patients' survival and irrespective of the order of
      administering CPT-11/L-OHP.

PMID- 19106600
TI  - Potential role of autophagy in behavioral changes of the flank organ.
AB  - The flank organ of the Syrian hamster, which shows a biodynamic response to
      androgen stimulation, is considered a good model for studying the androgen effect
      on sebaceous gland and hair. This organ is susceptible to programmed cell death
      (PCD), a prominent feature associated with sexual organ adjustment. We have
      recently shown the first direct evidence of a relationship between autophagy and
      morphological changes in androgen-dependent organs. In this work, animals were
      stabulated (housed) for two months under control conditions and, after sacrifice,
      autophagy markers, Beclin 1 and LC3-II, were evaluated. The results revealed
      autophagic processes in the flank organ of both sexes, especially in females, and
      no detectable caspase-3 activity. Therefore, these data indicated that
      macroautophagy, and not apoptosis, was the main mechanism by which the flank
      organ responds to androgen. Here, we present additional data on the flank organ,
      showing that the intensity of autophagy between genders depends on the length of
      stabulation. These data could indicate a role for autophagy in response to
      behavioral influences. A possible explanation and its implication in Syrian
      hamster social defeat are discussed in this addendum.

PMID- 19106601
TI  - YAP: at the crossroad between transformation and tumor suppression.
AB  - Yap is a small protein that binds to many transcription factors and modulates
      their activity. Yap was described to increase the ability of p73 in inducing
      apoptosis as a consequence of damage to the DNA, and therefore its activity was
      thought to favor tumor-suppression. However, other studies have recently shown a
      role for Yap in cell differentiation, cell transformation and in the regulation
      of organ size. It has been demonstrated that the Drosophila Hippo pathway has a
      mammalian equivalent, and that Yap is part of this pathway, where it might
      stimulate proliferation. In light of these new findings we ought to re-consider
      the role of Yap, which seems to be in service of several masters, and whose
      regulation--likely at the level of PTM--and cellular context might have a pivotal
      role in the choice of its partners and consequently on the final outcome.

PMID- 19106602
TI  - Stem cells do play with dice: a statistical physics view of transcription.
AB  - Embryonic stem cells display wide-spread pervasive transcriptional output. Here,
      we propose that multiple simultaneous transcriptional states underlay
      pluripotency.

PMID- 19106604
TI  - NALP3 inflammasome functional polymorphisms and gout susceptibility.
AB  - Gout is the most common autoinflammatory arthritis characterized by elevated
      serum urate and recurrent attacks of intra-articular crystal deposition of
      monosodium urate (MSU). Although the pathogenesis of gout is still unclear,
      accumulated studies indicate that genetic factors trigger gout development,
      including some susceptibility genes that control the production and clearance of
      urate and lead to hyperuricemia. However, the epidemiological evidence suggests
      that only less than 10% of hyperuricemia patients develop gout, indicating that
      other genes unrelated to the urate metabolism may also contribute to the diseases
      susceptibility. Accumulated evidences have implied that MSU crystal-induced
      inflammation is a paradigm of innate immunity and that NALP3 inflammasome, an
      innate immune complex containing NALP3, ASC and CARD-8, is involved in gout
      development. Recent studies suggest that NALP3 and CARD-8 functional mutations
      contribute to the development of autoinflammatory diseases including hereditary
      periodic fever syndrome, arthritis as well as hypertension susceptibility. Taking
      into account these genetic findings, here we would like to propose a novel
      hypothesis that functional mutations in NALP3 inflammasome may make NALP3
      inflammasome as attractive susceptibility candidates and genetic markers for
      gout. Further clinical genetic studies need to be performed to confirm the role
      of NALP3 inflammasome in the etiology of gout.

PMID- 19106603
TI  - The atypical CDK activator Spy1 regulates the intrinsic DNA damage response and
      is dependent upon p53 to inhibit apoptosis.
AB  - The intrinsic damage response is activated by DNA damage that arises during the
      cell division process. The ability of the cell to repair this damage during
      proliferation is important for normal cell growth and, when disrupted, may lead
      to increased mutagenesis and tumorigenesis. The atypical CDK activator, Spy1, was
      previously shown to promote cell survival, prevent apoptosis and inhibit
      checkpoint activation in response to DNA damage. Prior studies have shown that
      Spy1 is upregulated in breast carcinomas and accelerates mammary tumorigenesis in
      vivo. In this report, first, we demonstrate that the ability of Spy1 to inhibit
      apoptosis and bypass UV-induced checkpoint activation is dependent on the
      presence of the gene regulatory protein p53 and the CKI p21. Second, we
      demonstrate that Spy1 expression has the following effects: prevents repair of
      cyclobutane pyrimidine dimers through bypass of nucleotide excision repair;
      increases the cellular mutation frequency; and reduces the formation of cyclin E
      induced gammaH2A.X foci. Lastly, we show that knockdown of endogenous Spy1 leads
      to gammaH2A.X foci formation, Chk1 phosphorylation and proliferation defects,
      demonstrating a functional role for Spy1 in the intrinsic DNA damage response.
      These results also demonstrate that Spy1 fulfills a novel regulatory role in the
      intrinsic DNA damage response and maintains the balance between checkpoint
      activation, apoptosis, repair and cell cycle progression in response to exogenous
      or intrinsic damage. Furthermore, the overexpression of Spy1 as a contributing
      factor in cancer progression will most likely be confined to p53-positive cells.

PMID- 19106605
TI  - The many faces of shugoshin, the "guardian spirit," in chromosome segregation.
AB  - Since it was first identified in Drosophila as a centromeric protein, MEI
      S332/Shugoshin (Sgo1) has been an enigma. It is neither a kinase nor a
      phosphatase, but Sgo1's many functions are often attributable to protein-protein
      interactions that require Sgo1's presence to localize and/or function properly in
      a timely manner. Though much has been reported about Sgo1's role in ensuring
      proper genome segregation through its regulatory role in maintaining cohesion
      through protection of centromeric cohesin, several additional functions have been
      identified that are less well characterized. In higher eukaryotes Sgo2 and a
      splice variant of Sgo1 make up a small family of shugoshin proteins, whereas in
      budding yeast a single Sgo1 exists, and available data suggest that the many
      functions carried out by Sgo2 and the splice variant are handled exclusively by
      the Sgo1 homolog in yeast. In fact, the function of the mammalian splice variant
      is the factor that has revealed a new possible role for shugoshin in centrosome
      regulation, which may be related mechanistically to its task in protection of
      centromeric cohesin. New evidence in budding yeast supports this line of
      reasoning, which may represent an exciting new advance in exposing the myriad
      faces of the guardian spirit.

PMID- 19106606
TI  - Dimerization of the core domain of the p53 family: a computational study.
AB  - Computational models reveal the structural origins of cooperativity in the
      association of the DNA binding domains (DBD) of p53 (and its two homologues p63
      and p73) with consensus DNA. In agreement with experiments they show that
      cooperativity, as defined by sequential binding of monomers to DNA is strong for
      p53 and weak for homologues p63 and p73. Computations also suggest that
      cooperativity can arise from the dimerization of the DBD prior to binding the DNA
      for all 3 family members. Dimerization between the DBDs is driven by packing
      interactions originating in residues of helix H1 and loop L3, while DNA binding
      itself is dominated by local and global electrostatics. Calculations further
      suggest that low affinity oligomerization of the p53 DBD can precede the
      oligomerization of the tetramerization domain (TD). During synthesis of multiple
      chains on the polysome, this may increase fidelity by reducing the possibility of
      the highly hydrophobic TD from nonspecific aggregation. Mutations have been
      suggested to test these findings.

PMID- 19106607
TI  - Loss of p21 CDKN1A impairs entry to quiescence and activates a DNA damage
      response in normal fibroblasts induced to quiescence.
AB  - The cell cycle inhibitor p21(CDKN1A) induces cell cycle arrest under different
      conditions, including senescence and terminal differentiation. Still debated is
      its involvement in the reversible transition from proliferation to a non-dividing
      quiescent state (G(0)), in which a significant role has been attributed to cell
      cycle inhibitor p27(CDKN1B). Here we provide evidence showing that high p21
      protein levels are necessary to enter and maintain the quiescence state following
      contact inhibition and growth factor withdrawal. In fact, entry into quiescence
      was impaired, both in human fibroblasts in which p21 gene has been deleted, or
      protein expression knocked-down by RNA interference. Importantly, in the absence
      of p21, human fibroblasts activate a DNA damage-like signalling pathway, as shown
      by phosphorylation of histone H2AX and Chk1 proteins. In addition, we show that
      in the absence of p21, checkpoint is activated by an unscheduled entry into S
      phase, with a reduced efficiency in DNA maturation, in the presence of high c-myc
      protein levels. These results highlight the role of p21 in counteracting
      inappropriate proliferation stimuli for genome stability maintenance.

PMID- 19106608
TI  - Transforming growth factor beta (TGFbeta)-induced apoptosis: the rise & fall of
      Bim.
AB  - Transforming growth factor beta (TGFbeta) regulates essential cellular functions
      such as cellular proliferation, differentiation and apoptosis. Multiple apoptotic
      mediators and signaling pathways have been implicated in TGFbeta-induced
      apoptosis. Bim, a BH3-only protein, is critical for apoptosis in a variety of
      cell types. In resting cells, BimEL expression levels, the major and most
      abundant isoform, are controlled by Erk1/2-mediated phosphorylation, which
      targets BimEL for ubiquitination and degradation. We previously reported that
      TGFbeta induces the expression of the pro-apoptotic protein Bim through a Smad3
      dependent mechanism to induce cell death in B-lymphocytes. A number of studies
      have shown TGFbeta to cause transcriptional induction of Bim in many cell types.
      Recently, we demonstrated that, in addition to its transcriptional effects on
      Bim, TGFbeta induces a MAPK phosphatase (MKP), MKP2/DUSP4, to rapidly increase
      BimEL levels by inactivation of Erk1/2, resulting in dephosphorylation and escape
      of BimEL from ubiquitin-mediated degradation. Our findings are of importance not
      only in the context that we implicate TGFbeta to increase BimEL levels through
      both an immediate post-translational regulatory mechanism and a long-term effect
      through transcriptional induction, but also in the context of implicating MKPs as
      regulatory players in apoptosis. Here we summarize these recent findings and
      their significance to our understanding of how TGFbeta mediates apoptosis, and we
      explore the possible regulatory mechanisms controlling Bim expression levels.

PMID- 19106609
TI  - Overcoming resistance to tyrosine kinase inhibitors: lessons learned from cancer
      cells treated with EGFR antagonists.
AB  - Tyrosine kinase inhibitors (TKIs) are effective anti-cancer therapies but
      resistance to these agents eventually develops. Several models of resistance to
      TKIs have been studied including resistance to EGFR inhibitors. Recent studies in
      EGFR-dependent A431 cells found upregulation of the IGF1R pathway as a mechanism
      to overcome blockade of EGFR. This was associated with amplification of IGF1R
      signaling and recovery of downstream PI3K-AKT activation. This work adds to a
      growing body of cell lines in culture that have provided insights into mechanisms
      of resistance that can be interrogated in primary tumors in patients. In this
      review, these model systems and their applicability to human cancers, as well as
      strategies to identify and overcome resistance to TKIs, are discussed.

PMID- 19106610
TI  - Dyskerin, telomerase and the DNA damage response.
AB  - The bone marrow failure syndrome Dyskeratosis congenita (DC), though rare, has
      attracted a great deal of attention in the last few years because it is caused by
      mutations in genes whose products are involved in telomere maintenance. The
      disease presents with a variety of features that can all be due to failure of
      tissues that require constant renewal via stem cell activity. It is thought this
      is caused by defects in telomere maintenance leading eventually to cell cycle
      arrest or cell death caused by critically short telomeres. The most common form
      of DC is the X-linked form caused by mutations in DKC1 encoding the nucleolar
      protein, dyskerin. We recently reported a mouse model of the X-linked form of the
      disease in which females heterozygous for a mutation that copies a human
      pathogenic mutation showed a growth disadvantage in cells expressing the mutant
      dyskerin. This growth disadvantage, which was associated with an enhanced DNA
      damage response, was dependent on telomerase but appeared to be independent of
      telomere shortening. Here we discuss these results in terms of the role of
      dyskerin in telomere maintenance and the possible role that the DNA damage
      response plays in the pathogenesis of DC.

PMID- 19106611
TI  - Replication licensing promotes cyclin D1 expression and G1 progression in
      untransformed human cells.
AB  - Defects in DNA replication are implicated as early and causal events in
      malignancy. However, the immediate effects of impaired DNA replication licensing
      on cell cycle progression of non-malignant human cells are unknown. Therefore, we
      have investigated the acute effects of Mcm7 ablation using synchronized cultures
      of untransformed Human Dermal Fibroblasts (HDF). Mcm7 ablation elicited a G(1)
      delay associated with impaired activation of CDK4 and CDK2 and reduced Rb
      phosphorylation. The cell cycle delay of Mcm7-ablated cells was not associated
      with a DNA damage response. However, levels of cyclin D1 mRNA were specifically
      reduced and binding of RNA Polymerase II to the CYCD1 promoter was decreased in
      Mcm7-depleted cells. Similar to Mcm7-deficiency, Mcm2- or Cdc6-depletion led to
      impaired cyclin D expression. Ectopic overexpression of Cdc6 in quiescent cells
      promoted cyclin D1 expression, CDK4 activation and G(1) progression. Therefore
      timely and efficient expression of cyclin D1 during G(1) phase requires
      replication licensing. Reconstitution of cyclin D1 expression was insufficient to
      correct the G(1) delay of Mcm7-depleted cells, indicating that additional cell
      cycle events during G(1) are dependent on replication licensing. However, ectopic
      expression of the HPV-E7 oncoprotein, and the resulting bypass of the requirement
      for cyclin D1-Rb signaling enabled Mcm7-depleted cells to enter S-phase. HPV-E7
      induced S-phase entry of Mcm7-depleted cells led to a DNA damage response, a
      hallmark of pre-malignancy. Taken together, our results suggest the existence of
      a 'replication licensing restriction point' that couples pre-RC assembly with
      G(1) progression in normal cells to minimize replication stress, DNA damage and
      tumorigenesis.

PMID- 19106613
TI  - Deregulated expression of miR-26a and Ezh2 in rhabdomyosarcoma.

PMID- 19106612
TI  - Identification of two independent SUMO-interacting motifs in Daxx: evolutionary
      conservation from Drosophila to humans and their biochemical functions.
AB  - Daxx is essential for embryonic development and implicated in apoptosis and
      transcriptional regulation. It is found only in the animal kingdom and appears to
      arise first in insects. In the Drosophila genus, the Daxx orthologs are much
      larger than those in other species. Here we show that in addition to a conserved
      core of approximately 200 residues, Daxx possesses several conserved domains and
      two essentially invariable short SUMO-interacting motifs (SIMs), each located at
      one or the other terminus of the protein. Both can independently interact with
      SUMO. The Daxx I7/733K double mutant with one mutation in each of the two SIMs no
      longer interacts with SUMO. Daxx interacts with Ubc9 and this interaction
      strictly requires at least one SIM. Interestingly, the Ubc9 H20D mutation that
      abolishes non-covalent Ubc9-SUMO interaction also interrupts Daxx-Ubc9
      interaction. Thus, SUMO serves as the intermediate for Daxx-Ubc9 interaction.
      Surprisingly, Daxx I7/733K double mutant could still colocalize with PML.
      Furthermore, wt Daxx also strongly colocalizes with PMLDeltaS mutant, in which
      all three sumoylation sites are mutated, whereas PMLDeltaS only weakly
      colocalizes with Daxx I7/733K mutant, suggesting that SIM-SUMO interaction is not
      essential for but enhances PML-Daxx interaction. Remarkably, Daxx strongly
      stimulates c-Jun-mediated transcription and both SIMs are required for this
      stimulation. PML also activates c-Jun, which requires all three sumoylation
      sites. Coexpression of Daxx and PML revealed that they independently regulate c
      Jun, with Daxx exerting a dominant role. These results suggest that the conserved
      SIMs are involved in mediating protein-protein interactions that underlie Daxx's
      diverse cellular functions.

PMID- 19106614
TI  - Human and mouse hair follicles contain both multipotent and monopotent stem
      cells.

PMID- 19106615
TI  - Proteomic identification of carboxypeptidase E connects lipid-induced beta-cell
      apoptosis and dysfunction in type 2 diabetes.
AB  - Type 2 diabetes occurs when the endocrine pancreas can no longer secrete enough
      insulin to maintain glucose and lipid homeostasis. This is likely due to
      cumulative defects in beta-cell fate and function, as well as insulin resistance.
      A number of recent studies, including ones from our group, have used unbiased
      proteomic, genomic and genetic approaches to unravel the mechanisms by which
      hyperlipidemia causes beta-cell apoptosis and dysfunction. It is clear from these
      studies and others, that there are multiple pathways by which fatty acids such as
      palmitate can lead to beta-cell dysfunction and death. In the present article, we
      highlight the role for dysfunction in the ER and secretory pathway in the toxic
      effects of free fatty acids. Recent work has shown that the rapid degradation of
      carboxypeptidase E plays a significant role in beta-cell death in response to the
      free fatty acid palmitate. These newly identified targets of beta-cell
      lipotoxicity present novel avenues for research and therapeutic intervention.

PMID- 19106617
TI  - Cloning and expression of a calcium-activated chloride channel reveal  a novel
      protein candidate.

PMID- 19106616
TI  - The p53 mRNA-Mdm2 interaction.
AB  - The E3 ligase Mdm2 is a key regulator of p53 activity via a complex regulatory
      feedback system that involves all levels of expression control including
      transcription, mRNA translation and protein degradation. Best known is the effect
      of p53 on Mdm2 transcription and the capacity of Mdm2 to target p53 for
      degradation, but more recently the role of Mdm2 as a positive regulator of p53
      activity has also started to emerge. Mdm2 stimulates p53 mRNA translation by
      binding the p53 mRNA and, interestingly, this interaction also suppresses Mdm2's
      capacity to promote p53 polyubiquitination and degradation. Another interesting
      aspect of the p53 mRNA-Mdm2 interaction is that the p53 mRNA sequence encoding
      the amino acids which bind the N-terminus of Mdm2 is the same that interacts with
      the Mdm2 RING domain. Indeed, the regulatory elements for controlling Mdm2
      dependent expression of p53 are derived from the same p53 genomic sequence. In
      addition, the RNA binding and the E3 ligase domain of Mdm2 overlap, indicati that
      the two functions of Mdm2 to control p53 synthesis and degradation have co
      evolved in parallel in both p53 and Mdm2. Here we illustrate how the p53-Mdm2
      protein-protein and p53 mRNA-Mdm2 interactions affect Mdm2-mediated control of
      p53 expression using the Phe19Ala p53 mutant. We discuss how the new insights
      into the regulation of p53 expression levels can help to shed light on the origin
      of this elegant feedback system and on the function of Mdm2 isoforms.

PMID- 19106618
TI  - Functional properties of the CaV1.2 calcium channel activated by calmodulin in
      the absence of alpha2delta subunits.
AB  - Voltage-activated CaV1.2 calcium channels require association of the pore-forming
      alpha1C subunit with accessory CaVbeta and alpha2delta subunits. Binding of a
      single calmodulin (CaM) to alpha1C supports Ca2+-dependent inactivation (CDI).
      The human CaV1.2 channel is silent in the absence of CaVbeta and/or alpha2delta.
      Recently, we found that coexpression of exogenous CaM (CaMex) supports plasma
      membrane targeting, gating facilitation and CDI of the channel in the absence of
      CaVbeta. Here we discovered that CaMex and its Ca2+-insensitive mutant (CaM1234)
      rendered active alpha1C/CaVbeta channel in the absence of alpha2delta.
      Coexpression of CaMex with alpha1C and beta2d in calcium-channel-free COS-1 cells
      recovered gating of the channel and supported CDI. Voltage-dependence of
      activation was shifted by approximately +40 mV to depolarization potentials. The
      calcium current reached maximum at +40 mV (20 mM Ca2+) and exhibited
      approximately 3 times slower activation and 5 times slower inactivation kinetics
      compared to the wild-type channel. Furthermore, both CaMex and CaM1234
      accelerated recovery from inactivation and induced facilitation of the calcium
      current by strong depolarization prepulse, the properties absent from the human
      vascular/neuronal CaV1.2 channel. The data suggest a previously unknown action of
      CaM that in the presence of CaVbeta; translates into activation of the
      alpha2delta-deficient calcium channel and alteration of its properties.

PMID- 19106619
TI  - Known turnover and translation regulatory RNA-binding proteins interact with the
      3' UTR of SECIS-binding protein 2.
AB  - The human selenoproteome is composed of approximately 25 selenoproteins, which
      cotranslationally incorporate selenocysteine, the 21st amino acid. Selenoprotein
      expression requires an unusual translation mechanism, as selenocysteine is
      encoded by the UGA stop codon. SECIS-binding protein 2 (SBP2) is an essential
      component of the selenocysteine insertion machinery. SBP2 is also the only factor
      known to differentiate among selenoprotein mRNAs, thereby modulating the relative
      expression of the individual selenoproteins. Here, we show that expression of
      SBP2 protein varies widely across tissues and cell types examined, despite
      previous observations of only modest variation in SBP2 mRNA levels. This
      discrepancy between SBP2 mRNA and protein levels implies translational
      regulation, which is often mediated via untranslated regions (UTRs) in regulated
      transcripts. We have identified multiple sequences in the SBP2 3' UTR that are
      highly conserved. The proximal short conserved region is GU rich and was
      subsequently shown to be a binding site for CUG-BP1. The distal half of the 3'
      UTR is largely conserved, and multiple proteins interact with this region. One of
      these proteins was identified as HuR. Both CUG-BP1 and HuR are members of the
      Turnover and Translation Regulatory RNA-Binding Protein family (TTR-RBP). Members
      of this protein family are linked by the common ability to rapidly effect gene
      expression through alterations in the stability and translatability of target
      mRNAs. The identification of CUG-BP1 and HuR as factors that bind to the SBP2 3'
      UTR suggests that TTR-RBPs play a role in the regulation of SBP2, which then
      dictates the expression of the selenoproteome.

PMID- 19106620
TI  - RNA-mediated chaperone type for de novo protein folding.
AB  - Traditionally the principles of protein folding in vivo have been obtained
      largely from molecular chaperone studies. Through extensive studies on molecular
      chaperones, it becomes clear that most proteins can fold without their assistance
      in vivo, suggesting the existence of other chaperone types and mechanisms. Since
      all nascent polypeptides are linked to the ribosomes, protein folding in vivo
      should be understood in the context of vectorial protein synthesis and linkage of
      nascent chains to ribosome whose major components and basic structural frames are
      RNAs. Here we introduce a novel RNA-mediated chaperone type and a possible
      molecular basis for how RNAs can exert chaperoning effect on their linked
      aggregation-prone polypeptides. Extending potential chaperoning role of ribosome
      on the bound nascent polypeptide in a cis-acting manner, the findings further
      suggest a novel function of RNA molecules for protein folding inside cells. RNA
      interaction-mediated stabilization of folding intermediate against aggregation
      provides new insights into de novo protein folding in vivo and further extends
      the functional diversity of RNA molecules.

PMID- 19106621
TI  - Translating organellar glutamine codons: a case by case scenario?
AB  - Aminoacyl-tRNAs are generally formed by direct attachment of an amino acid to
      tRNAs by aminoacyl-tRNA synthetases, but glutaminyl-tRNA (Q-tRNA) is an exception
      to this rule. Glutaminyl-tRNA(Gln) (Q-tRNA(Q)) is formed by this direct pathway
      in the eukaryotic cytosol and in a small subset of bacteria, but is formed by an
      indirect transamidation pathway in most bacteria and archaea. To date it is
      almost impossible to predict what pathway generates organellar Q-tRNA(Q) in a
      given eukaryote. All eukaryotic genomes sequenced so far, display a single
      glutaminyl-tRNA synthetase (QRS) gene which is at least responsible for the
      cytosolic QRS activity, as well as a gene coding for a mitochondrial ortholog of
      the essential GatB subunit of the tRNA-dependent amidotransferase (AdT). Indeed,
      QRS activity was found in protozoan mitochondria while AdT activity was
      characterized in plant organelles. The pathway for Q-tRNA(Q) synthesis in yeast
      and mammals mitochondria is still questionable.

PMID- 19106622
TI  - The NFAR's (nuclear factors associated with dsRNA): evolutionarily conserved
      members of the dsRNA binding protein family.
AB  - The dsRNA binding protein (DRBP) family comprise one or more evolutionarily
      conserved dsRNA-binding domains (DRBD) of approximately 65-68 amino acids, are
      found in both eukaryotes and prokaryotes and are even encoded by plants and
      viruses. DRBP's do not recognize specific nucleotide sequences and primarily
      interact with approximately 11-16 base pairs present within A-form double helix
      RNAs, which can include ssRNA's with extensive secondary structure. The DRBP
      family include TRBP (TAR RNA binding protein), PKR (protein kinase activated by
      dsRNA), PACT (Protein Activator of PKR), ADAR (Adenosine deaminases acting on
      RNA), and the RNase III family including DICER, which collectively play important
      roles in mRNA elongation, RNA interference (RNAi), mRNA editing, stability,
      splicing and/or export and translation. Here, we focus on the role of DRBP's
      referred to as the NFARs (Nuclear Factors associated with dsRNA) which are
      translated from two major alternatively spliced products encoded from a single
      gene. Evidence indicates that the NFAR proteins play crucial roles in mRNA post
      transcriptional regulation, including mRNA stability, export and translation and
      may also have an important function in host defense.

PMID- 19106623
TI  - A survey of nematode SmY RNAs.
AB  - SmY RNAs are a family of approximately 70-90 nt small nuclear RNAs found in
      nematodes. In C. elegans, SmY RNAs copurify in a small ribonucleoprotein (snRNP)
      complex related to the SL1 and SL2 snRNPs that are involved in nematode mRNA
      trans-splicing. Here we describe a comprehensive computational analysis of SmY
      RNA homologs found in the currently available genome sequences. We identify
      homologs in all sequenced nematode genomes in class Chromadorea. We are unable to
      identify homologs in a more distantly related nematode species, Trichinella
      spiralis (class: Dorylaimia), and in representatives of non-nematode phyla that
      use trans-splicing. Using comparative RNA sequence analysis, we infer a conserved
      consensus SmY RNA secondary structure consisting of two stems flanking a
      consensus Sm protein binding site. A representative seed alignment of the SmY RNA
      family, annotated with the inferred consensus secondary structure, has been
      deposited with the Rfam RNA families database.

PMID- 19106624
TI  - Reconciling contradictory reports regarding translation of BACE1 mRNA: initiation
      mechanism is altered by different expression systems.
AB  - We previously showed that translation from the rat BACE1 5' leader is cap
      dependent and that four AUG codons (AUG1-4) in the 5' leader were bypassed,
      partially or completely, depending on the cell line. Two other groups reported
      comparable results with human BACE1 sequences in different cell lines, although
      different mechanisms were postulated. In contrast, a third group working with the
      human sequence reported that most translation events are initiated at AUG2. Using
      reporter constructs with the rat BACE1 5' leader in rat cells, we now show that
      this apparent discrepancy between studies can be explained by the use of
      different expression systems and differences in interpretation. When reporter
      constructs were transcribed in the nucleus, the upstream AUG codons did not
      affect translation, but when mRNAs were transcribed in the cytoplasm or when in
      vitro transcripts were transfected into cells, the upstream AUG codons inhibited
      translation. These findings suggest that when transcription occurs in the
      nucleus, the BACE1 mRNA initiates translation by a shunting mechanism. The
      results are less consistent with either leaky scanning or reinitiation and
      provide a caveat against the use of cytoplasmic expression systems or RNA
      transfection for analyses of translation initiation.

PMID- 19106626
TI  - The antidiabetic drug metformin suppresses HER2 (erbB-2) oncoprotein
      overexpression via inhibition of the mTOR effector p70S6K1 in human breast
      carcinoma cells.
AB  - Population studies have revealed that treatment with the antidiabetic drug
      metformin significantly associates with reduced breast cancer risk. Animal
      studies have shown that metformin suppresses the development of mammary
      carcinomas in transgenic female mice carrying a HER2 oncogene, but not that of
      spontaneous tumors. We herein demonstrate that HER2 oncoprotein itself may
      represent a key cellular target involved in the anti-breast cancer actions of
      metformin. First, ectopical overexpression of HER2 oncogene significantly
      enhances metformin-induced breast cancer cell growth inhibition. Second,
      metformin treatment drastically downregulates HER2 protein levels (up to 85%
      reduction) in a dose- and time-dependent manner. Metformin-induced inhibition of
      HER2 take places regardless the molecular mechanism contributing to HER2
      overexpression (i.e., human HER2 cDNA exogenously driven by a viral promoter and
      naturally occurring endogenous HER2 gene amplification). Mechanistically,
      metformin-induced suppression of HER2 overexpression appears to occur via direct
      (AMPK-independent) inhibition of p70S6K1 activity. Compound C- and small
      interference RNA (siRNA)-induced blockade of AMPK activity/expression fail to
      prevent the anti-HER2 effect of metformin while AMPK hyperactivation following
      exposure to the AMP analog AICAR is not sufficient to downregulate HER2
      expression. HER2-positive breast cancer cells transfected with p70S6K1 siRNA
      become completely refractory to metformin-induced HER2 suppression. Of note, co
      incubation with agents that block reactive oxygen species (ROS) production (e.g.,
      N-acetylcysteine) dramatically enhanced the ability of metformin to decrease HER2
      expression. From the perspective of chemoprevention, these findings altogether
      suggest that metformin might exert a protective mostly confined to the HER2
      positive breast cancer subtype. From the perspective of intervention, the
      presence/absence of molecular hallmarks such as HER2 overexpression and/or
      p70S6K1 hyperactivation might dictate alternative responses in metformin-based
      treatment of early breast cancer. The importance of mTOR/p70S6K1-sensed ROS
      status at mediating the anti-oncogenic effects of metformin might represent a
      previously unrecognized linkage molecularly connecting its anti-aging and anti
      cancer actions.

PMID- 19106625
TI  - MicroRNAs identified in highly purified liver-derived mitochondria may play a
      role in apoptosis.
AB  - MicroRNAs (miRNAs) are a class of small approximately 22 nt noncoding (nc) RNAs
      that regulate gene expression post-transcriptionally by direct binding to target
      sites on mRNAs. They comprise more than 1,000 novel species in mammalian cells
      and exert their function by modulating gene expression through several different
      mechanisms, including translational inhibition, and/or degradation of target
      mRNAs. Mitochondria maintain and express their own genome, which is distinct from
      the nuclear transcriptional and translational apparatus. Thus, they provide a
      potential site for miRNA mediated post-transcriptional regulation. To determine
      whether they maintain a unique miRNA population, we examined the miRNA profile
      from highly purified and RNase treated mitochondria from adult rat liver. Fifteen
      miRNAs were identified by microarray analysis of which, five were confirmed by
      TaqMan 5'nuclease assays using rat specific probes. Functional analysis of the
      miRNAs indicated that they were not targeted to the mitochondrial genome nor were
      they complementary to nuclear RNAs encoding mitochondrial proteins. Rather, the
      mitochondria-associated miRNAs appear to be involved in the expression of genes
      associated with apoptosis, cell proliferation, and differentiation. Given the
      central role that mitochondria play in apoptosis, the results suggest that they
      might serve as reservoirs of select miRNAs that may modulate these processes in a
      coordinate fashion.

PMID- 19106627
TI  - RNase P: increased versatility through protein complexity?
AB  - Ribonuclease P (RNase P) is an essential enzyme that catalyzes the 5'
      endonucleolytic cleavage of precursor transfer RNAs (pretRNAs). It is found in
      all phylogenetic domains: bacteria, archaea and eukaryotes. The bacterial enzyme
      consists of a single, catalytic RNA subunit and one small protein, while the
      archaeal and eukaryotic enzymes have 4-10 proteins in addition to a similar RNA
      subunit. The bacterial RNA acts as a ribozyme at high salt in vitro; however the
      added protein optimizes kinetics and makes specific contacts with the pre-tRNA
      substrate. The bacterial protein subunit also appears to be required for the
      processing of non-tRNA substrates by broadening recognition tolerance. In
      addition, the immense increase in protein content in the eukaryotic enzymes
      suggests substantially enlarged capacity for recognition of additional
      substrates. Recently intron-encoded box C/D snoRNAs were shown to be likely
      substrates for RNase P, with several lines of evidence suggesting that the
      nuclear holoenzyme binds tightly to, and can cleave single-stranded RNA in a
      sequence dependent fashion. The possible involvement of RNase P in additional RNA
      processing or turnover pathways would be consistent with previous findings that
      RNase MRP, a variant of RNase P that has evolved to participate in ribosomal RNA
      processing, is also involved in turnover of specific messenger RNAs. Here,
      involvement of RNase P in multiple RNA processing pathways is discussed.

PMID- 19106629
TI  - The current understanding of Ded1p/DDX3 homologs from yeast to human.
AB  - DExD/H-box RNA helicases are involved in almost all steps of the eukaryotic mRNA
      biogenesis. The DEAD-box protein Ded1p/DDX3 is conserved from yeast to human.
      Various lines of genetic and biochemical evidence have indicated a role of the
      yeast Ded1p in translation and, most likely, in precursor mRNA splicing as well.
      In contrast, although recent studies have begun to reveal the function of the
      mammalian DDX3 in translation control, its exact role remains vague and even
      controversial. Here, we review these findings and particularly discuss the
      functional aspects of Ded1p/DDX3 in translation control.

PMID- 19106628
TI  - Nuclear phosphoinositide signaling regulates messenger RNA export.
AB  - Messenger RNA export from the nucleus to the cytoplasm plays an essential role in
      linking transcription to translation and consequently regulation of protein
      expression. mRNA export requires a series of events: pre-mRNA processing,
      ribonucleoprotein targeting to the NPC (nuclear pore complexes), and
      translocation through nuclear pores to the cytoplasm. Interestingly, the
      conventional nuclear export machinery, exportins and the Ran GTPase, is not
      required for mRNA export. Instead, a protein complex consisting of a number of
      RNA binding proteins is essential for this event including the Aly/REF protein.
      Phosphoinositide signaling regulates a variety of cellular functions including
      pre-mRNA splicing and mRNA export. In fact, a phospholipase C-dependent inositol
      polyphosphate kinase pathway is required for efficient mRNA export. Recently, we
      showed that Aly is a physiological target of nuclear phosphoinositide-3-kinase
      (PI3K) signaling, which regulates Aly localization as well as Aly function in
      cell proliferation and mRNA export through nuclear Akt-mediated phosphorylation
      and phosphoinositide association. Hence, water-soluble inositol polyphosphates
      and phosphatidylinositol lipids play pivotal roles in modulating mRNA export.

PMID- 19106630
TI  - Transcriptional control of microRNA expression in C. elegans: promoting better
      understanding.
AB  - Transcriptional regulation of microRNA (miRNA) expression is one of the least
      understood aspects of miRNA biogenesis. In C. elegans the list of miRNAs whose
      transcriptional control has been described in some detail is currently limited to
      four: let-7, lin-4, lsy-6, and mir-61. Each of these genes has been shown
      experimentally to be transcriptionaly regulated by cis- and/or trans-acting
      factors that either promote or inhibit expression. Additionally, computational
      methods based on conservation among miRNA genes have yielded predicted regulatory
      sequences in C. elegans that may function to regulate miRNA expression on a
      genome-wide scale.

PMID- 19106631
TI  - Structure and activity of the internal ribosome entry site within the human p27
      Kip1 5'-untranslated region.
AB  - The cyclin dependent kinase inhibitor p27(Kip1) is a key cell cycle regulatory
      protein that is often downregulated in cancer cells. The cellular levels of
      p27(Kip1) are regulated, in part, through translational control mechanisms. The
      5'-UTR of the p27(Kip1) mRNA is known to harbor an IRES that may facilitate
      expression of p27(Kip1) under conditions of stress such as loss of cell adhesion
      or growth factor and nutrient deprivation. The results presented here further
      characterize the p27(Kip1) 5'-UTR and its IRES activity. We confirm that the
      major transcription start site of the p27(Kip1) gene produces an mRNA with a 5'
      UTR of approximately 472 nucleotides. Other minor transcripts are also observed
      but the 472 nucleotide 5'-UTR displays the highest IRES activity. A structural
      model for the 472 nucleotide 5'-UTR was derived from nuclease digestion patterns
      coupled with MFOLD secondary structural prediction software. These results
      indicate that the 5'-UTR has significant secondary structure but also contains a
      large single-stranded loop that extends from nucleotides -31 to -66 relative to
      the start codon. Mapping of the ribosome entry window indicates that the ribosome
      is recruited to this single-stranded loop. The single-stranded loop also includes
      a U-rich sequence that has previously been shown to bind several proteins,
      including HuR. This is significant because HuR has previously been shown to
      inhibit p27(Kip1) IRES activity and cause downregulation of endogenous p27(Kip1)
      protein levels. Thus HuR may inhibit IRES activity by blocking the ribosome entry
      site.

PMID- 19106632
TI  - Gamma-radiation (GR) triggers a unique gene expression profile associated with
      cell death compared to proton radiation (PR) in mice in vivo.
AB  - Proton radiation (PR) therapy offers a number of potential advantages over
      conventional (photon) gamma-radiation (GR) therapy for cancer, due to a more
      localized delivery of the radiation dose. However, the pathophysiological effects
      following PR-exposure are less well characterized than those of GR-exposure and
      the molecular changes associated with the acute apoptotic effects in mice in vivo
      following PR have not been elucidated. Previous studies have estimated the RBE of
      protons for various in vivo and in vitro endpoints at between 1.1 and 1.3. We
      assumed an RBE of 1.1 for the endpoints to be evaluated in these studies. Based
      on this assumption, ICR mice were treated with whole-body doses of GR (1.1 and
      7.0 Gy) and PR (1.0 and 6.4 Gy) that were expected to represent RBE-weighted
      doses. The bone marrow, thymus, spleen and GI-tract were isolated and processed
      for histology and immunohistochemistry. The apoptotic responses varied greatly
      between GR and PR in a tissue- and dose-dependent manner. Surprisingly,cell death
      in the splenic white pulp was consistently lower in PR-treated animals compared
      to animals treated with GR. This was in spite of an increased presence of damaged
      DNA following PR as determined by staining for gammaH2AX and phospho-ATM.
      Interestingly, both PR and GR triggered nuclear accumulation of p53 and no
      significant differences were found in the majority of the known pro-apoptotic p53
      target genes in the spleens of treated mice. However, GR uniquely triggered a pro
      apoptotic expression profile including expression of the pro-apoptotic, p53- and
      interferon stimulated target gene Bcl-G. In contrast to PR, GR may, in a cell
      type specific manner, trigger a more diverse non-random stress-response that
      mediates apoptosis partially independent of the extent of DNA damage.

PMID- 19106633
TI  - TNFSF10 (TRAIL), a p53 target gene that mediates p53-dependent cell  death.
AB  - We have identified TNFSF10 (TRAIL) as a p53-transcriptional target gene. There
      are two p53 DNA-binding sites in the human TNFSF10 promoter region, at 346 and
      625 bp upstream of the transcription start site. A human p53-expressing
      adenovirus (Ad-p53) induced TRAIL mRNA and protein expression in HCT116 p53-/-
      human colon cancer cells. A human TRAIL-promoter reporter assay showed increased
      luciferase activity with the promoter vector that contains two p53 DNA-binding
      motifs,following Ad-p53 infection, compared to the control adenovirus infection.
      Using HCT116 cells, gene silencing of TNFSF10 by siRNA suppressed caspase 3 and 7
      activity, even after treatment with the DNA-damaging chemotherapeutic agent
      adriamycin. TRAIL protein expression was elevated in adriamycin-treated breast
      cancer cells. In vivo, TRAIL expression was induced in mouse natural killer cells
      at 24 hours after systemic treatment with 5-Fluorouracil. p53-dependent TRAIL
      induction in natural killer cells after chemotherapy exposure provides a link
      between the tumor suppressor p53 and the host immune response during cancer
      therapy as well as a paracrine-mediated cell-extrinsic death response. Our
      findings provide new mechanistic insights into the signaling of p53-dependent
      cell death and tumor suppression, including the involvement of the host immune
      system and natural killer cells in vivo in the anti-tumor efficacy of
      chemotherapy.

PMID- 19106634
TI  - Role of PI3K/Akt signaling in TRAIL- and radiation-induced gastrointestinal
      apoptosis.
AB  - Activation of the PI3K/Akt pathway is associated with tumorigenesis and
      resistance to apoptosis and ionizing radiation (IR). We sought to characterize
      the effects of physiologic and genetic manipulation of Akt signaling on IR
      induced gastrointestinal (GI) apoptosis in mice. PI3K/Akt signaling is stimulated
      by insulin. We evaluated the time course of Akt stimulation by insulin and found
      it overlapped with protection from apoptosis induced by TRAIL (TNFalpha Related
      Apoptosis Inducing Ligand) in cell lines. Mice were treated with insulin and
      glucose and the kinetics of in vivo Akt stimulation were determined by phospho
      Akt (S473) (P-Akt) immunofluorescence in the gut. Irradiation of mice by five Gy
      at 30 minutes after insulin/glucose administration induced apoptosis in the
      crypts of the ileum and colon after six hours, but induced little apoptosis in
      the liver or esophagus. Pre-treatment with insulin and glucose did not
      significantly alter levels of IR-induced apoptosis in the gut. IR alone led to
      sustained increases in P-Akt in the gut at six hours, a protective response that
      may have precluded additional protection from insulin/glucose. In Akt1-/- mice,
      there was significantly more apoptosis in ileum crypts of irradiated mice
      compared to Akt1+/+ mice, suggesting a role for the pathway in the GI tract in
      response to IR. Taken together, modulation of the PI3K/Akt pathway may sensitize
      or protect against cancer therapies in both tumor and normal tissues.

PMID- 19106635
TI  - Non-genotoxic anti-neoplastic effects of ellipticine derivative NSC176327 in p53
      deficient human colon carcinoma cells involve stimulation of p73.
AB  - We previously performed a high-throughput screen using real-time noninvasive
      bioluminescence imaging of p53 transcriptional activity and identified a group of
      small molecules that trigger p53-like transcriptional responses in p53-deficient
      tumor cells. Here we further examined the anti-tumor effects of selected
      compounds in vitro and showed that NSC176327, a derivative of the cytotoxic plant
      alkaloid ellipticine, exhibited strong anti-neoplastic effect sin wild-type p53,
      p53-mutant or p53-deficient human colon cancer cells. NSC176327 was more potent
      at inhibiting tumor cell growth as compared to chemotherapeutic drugs and other
      ellipticine derivatives and induced cell cycle arrest and apoptosis.
      Surprisingly, unlike what is observed with the parent compound ellipticine, a DNA
      damage signaling response was not observed with NSC176327 as evidenced by lack of
      phosphorylated histone H2AX foci in NSC176327-treated tumor cells. NSC176327
      treatment caused a significant increase in p53-activated reporter signal in
      HCT116, SW620 and HCT116 p53-/- cells and upregulated DR5 and p21 protein
      expression. NSC176327 treatment also resulted in increased p73 protein expression
      and knockdown of transactivating isoforms of p73 in HCT116 p53-/- cells showed
      significant resistance to drug treatment. These results demonstrate an important
      role of p73 in the anti-tumor effects of NSC176327,and suggest that a close
      analogue of ellipticine may act by a non-genotoxic mechanism targeting the
      p53/p73 pathway as compared to the original parent compound that targets the same
      pathway.

PMID- 19106636
TI  - microRNAs and their potential target genes in leukemia pathogenesis.
AB  - Leukemia is the most common hematological malignancy, characterized by distorted
      proliferation and development of leukocytes and their precursors in the blood and
      bone marrow. Although impressive biologic advance has increased understanding of
      leukemogenesis, we know little regarding the pathogenic events leading to the
      initiation and progression of this disease. microRNAs (miRNAs) are now recognized
      as a class of small, non-protein-coding RNA molecules that can regulate the
      expression of many genes. The evolutionarily conserved small molecules play
      important roles in cellular development and function, through mediation of target
      gene repression. There is significant evidence showing that miRNAs play an
      important role in disease, especially in oncogenesis. Aberrant expression of
      miRNAs appears to be a common feature of haematological malignancies. Since the
      discovery of miR-15 and miR-16 in CLL, much effect has been done to investigate
      the small molecule in leukemia. Several research groups have shown differences in
      miRNA expression between normal and malignant cells in leukemia. So miRNAs may be
      involved in leukemia pathogenesis. Despite the recognition of their synthesis, we
      know little about their exact molecular function and the identifications of their
      target genes. Some targets of miRNAs are antiapoptotic genes such as Bcl2 and
      Tcl1. MiRNAs to these genes are natural antagonists and may be also applied in
      leukemia therapy. This article reviews the common science supporting miRNAs and
      their potential target genes in leukemia pathogenesis.

PMID- 19106637
TI  - Nelfinavir induces the unfolded protein response in ovarian cancer cells,
      resulting in ER vacuolization, cell cycle retardation and apoptosis.
AB  - Proteasome inhibitors and protease inhibitors are currently being discussed to be
      useful to sensitize drug-resistant cancer cells to chemotherapeutic agents or to
      act independently as single agents on drug-resistant cancer cells. We tested the
      effect of the clinically applied HIV protease inhibitor nelfinavir on ovarian
      cancer cells. Nelfinavir efficiently induced cell death in carboplatin-sensitive
      (SKOV3, OV-GH-5) and carboplatin-resistant (OVCAR3, OV-GH-1) ovarian cancer cell
      lines as well as in cancer biopsies and ascites samples from patients with
      recurrent ovarian cancer. Nelfinavir significantly changed the morphology of
      ovarian cancer cells, resulting in formation of large ER-derived vacuoles and
      induced upregulation of the hsp70 heat shock family member BiP (GRP78) which
      accumulated within swollen ER membranes. Upregulation of BiP and phosphorylation
      of eIF2alpha indicated induction of the unfolded protein response, which can
      cause cell cycle arrest and apoptosis. Correspondingly, we observed
      downregulation of cell cycle regulatory proteins after nelfinavir treatment,
      especially that of cyclin D3, and induction of apoptosis as confirmed by annexin
      binding. Because nelfinavir represents an already approved drug for use in humans
      with HIV infection, it could rapidly be tested in clinical studies as a potential
      treatment strategy against drug-resistant ovarian cancer.

PMID- 19106638
TI  - Therapeutic potential of various beta-glucan sources in conjunction with anti
      tumor monoclonal antibody in cancer therapy.
AB  - Combined beta-glucan with anti-tumor mAb therapy has demonstrated therapeutic
      efficacy in murine tumor models. The current study was designed to compare the
      therapeutic efficacy of various sources of beta-glucans. Our studies demonstrated
      that yeast beta-glucan, in combination with anti-tumor mAb, resulted in
      significantly smaller tumor burdens and achieved enhanced long-term survival
      compared to mAb alone or beta-glucan extracts from mushrooms. Further studies
      indicated that yeast beta-glucan particle was superior to mushroom extracts in
      inducing cytokine secretion, particularly IL-12 production in dendritic cells
      (DCs). In addition, results showed that cytokine production was markedly
      decreased in MyD88-deficient macrophages and DCs but not in complement receptor 3
      (CR3)-deficient mice. Our data suggest that yeast beta-glucan demonstrates much
      stronger adjuvant activity compared to mushroom beta-glucan extracts in tumor
      therapy. This effect of yeast beta-glucan may be in part ascribed to the cytokine
      secretion by DCs and macrophages and bioavailability of active beta-glucan
      moiety.

PMID- 19106639
TI  - cAMP and Pyk2 interact to regulate prostate cell proliferation and function.
AB  - In cultured prostate cancer cells cAMP blocks proliferation and induces
      neuroendocrine differentiation. Pyk2 expression inversely correlates with
      malignancy of prostate cancer. The aim of this study was to investigate the
      interaction between cAMP and Pyk2 in the prostate. EPN cells, a line derived from
      human normal prostate expressing Pyk2, and EPN-PKM3 cells, an EPN clone bearing a
      Pyk2 kinase-negative mutant, were adopted as model system. cAMP inhibited cell
      growth in both prostate cell lines, and activated Pyk2, but not ERK1/2, in EPN
      cells. cAMP treatment, abolished the activation of AKT1, an important component
      of the pro-survival pathway, in the EPN cells but not in EPN-PKM3 cells. Finally,
      upon cAMP treatment, EPN and EPN-PKM3 cells exhibited different expression
      patterns of HOX genes, an important network controlling cell identity. These data
      demonstrated for the first time that Pyk2 and cAMP interact in regulating
      prostate cell functions and in "keeping" prostate identity.

PMID- 19106641
TI  - CD40L gene transfer in immunotherapy of cancer: more than co-stimulation?

PMID- 19106640
TI  - Inhibition of RNA-dependent protein kinase (PKR) leads to cancer cell death and
      increases chemosensitivity.
AB  - RNA-dependent protein kinase is an interferon-induced, double-stranded (ds), RNA
      activated serine/threonine protein kinase involved in the eukaryotic response to
      viral infection. While PKR also functions in cellular differentiation, growth
      control and apoptosis, its role in human cancer remains poorly understood. To
      explore a role for PKR in human cancer, we evaluated PKR expression and function
      in a series of cancer cell lines from different tumor types. We observed that PKR
      protein expression is high in various cancer cells and low in normal cells.
      Knockdown of PKR protein expression by PKR siRNA induced cell death, indicating a
      PKR-dependent survival pathway under normal growth conditions. Inhibition of PKR
      signaling using a dominant negative adenoviral PKR mutant (Ad-Delta6PKR) also
      induced cancer cell apoptosis via a mechanism that blocks activation of AKT
      mediated survival while simultaneously inducing ER stress. ER stress-mediated
      apoptosis was evidenced by unregulated expression of phosphorylated JNK (p-JNK),
      phosphorylated cJun (p-cJun), and caspase-4 and was significantly reduced in
      cancer cells treated with JNK and caspase-4 inhibitors. We further demonstrated
      that inhibition of PKR signaling via either siRNA or Ad-Delta6PKR sensitizes
      cancer cells to etoposide or cisplatin-mediated cell death. Our results suggest a
      rationale to develop therapeutic strategies that target PKR signaling in human
      cancer cells.

PMID- 19106643
TI  - Epigenetic regulation of X-inactivation in human embryonic stem cells.
AB  - X chromosome inactivation (XCI) allows dosage compensation of the expression from
      sex chromosome in mammalian female cells. Although this mechanism is extensively
      studied in the mouse model organism, the corresponding mechanism during human
      development is largely unknown. The generation of human embryonic stem cells
      (hESCs) provides an invaluable tool to address early embryogenesis in humans.
      Even though hESCs were supposed to shed light on the XCI process in early human
      embryogenesis, previous studies largely indicated inconsistency in the status of
      XCI in these cells. Recently, new data suggested that in vitro culture might
      affect epigenetic mechanisms such as XCI. In this review we will present the
      existing data regarding XCI variations in hESC as compared to data from the mouse
      embryo and embryonic stem cells. We will also suggest possible explanations for
      the conflicting observations in the literature regarding XCI in hESCs.

PMID- 19106642
TI  - The HIF-1alpha C1772T polymorphism may be associated with susceptibility to
      clinically localised prostate cancer but not with elevated expression of hypoxic
      biomarkers.
AB  - We investigated the role of the C1772T polymorphisms in exon 12 of the Hypoxia
      inducible factor-1 alpha (HIF-1alpha) gene C1772T genotype in prostate cancer
      (PCa) and amplification of the hypoxic response. We identified the heterozygous
      germline CT genotype as an increased risk factor for clinically localised
      prostate cancer (Odds ratio = 6.2; p < 0.0001). While immunostaining intensity
      for HIF-1alpha and VEGF was significantly enhanced in 75% of PCa specimens when
      compared to matched benign specimens (p < 0.0001), the CT genotype did not
      modulate the kinetics of HIF-1alpha protein expression in hypoxia in vitro, and
      was not associated with enhanced expression of hypoxic biomarkers. This study
      provides the first evidence of an increased risk for clinically localised
      prostate cancer in men carrying the C1772T HIF-1alpha gene polymorphism. Although
      our results did not suggest an association between expression of hypoxic
      biomarkers and genotype status, the correlation may merit further investigation.

PMID- 19106644
TI  - Perturbation of genomic imprinting in oligozoospermia.
AB  - The role of epigenetic modifications in oligozoospermia and other disorders of
      spermatogenesis remains poorly understood. While a variety of environmental,
      nutritional and genetic abnormalities can cause oligozoospermia, a condition
      associated with infertility, it is unclear whether chromatin modifications might
      be also involved in impaired spermatogenesis. Several recent studies addressed
      this question and reported abnormal DNA methylation patterns in sperm from
      oligozoospermic men. Altered DNA methylation was detected specifically at
      sequence elements that control imprinted gene expression. This remarkable finding
      suggests that defects in spermatogenesis could be linked to the epigenetic
      regulation of imprinting in the male germ line. In addition, they raise concerns
      as to whether aberrant imprints in the male germ cells can have health
      implications for the next generation.

PMID- 19106645
TI  - Imprinting of tumor-suppressor genes in human placenta.
AB  - Transcriptional deregulation in cancer has been shown to be associated with
      epigenetic alterations, in particular to tumor-suppressor- gene (TSG) promoters.
      In contrast, DNA methylation of TSGs is not considered to be present in normal
      differentiated cells. Nevertheless, we previously showed that the promoter of the
      tumor-suppressor gene APC is methylated, for one allele only, in normal gastric
      cells. Recently, RASSF1A has been shown to be imprinted in normal human placenta.
      To clarify putative TSG methylation in the placenta, 23 normal placental tissues
      from the first trimester, both decidua and villi, and four normal non-gestational
      endometrium were screened for DNA methylation by methylation-sensitive single
      strand conformation analysis (MS-SSCA) and sequencing after bisulfite
      modification, on a panel of 12 genes known to be implicated in carcinogenesis. In
      all placental villi, four TSG promoters-APC, SFRP2, RASSF1A and WIF1-were
      hypermethylated, whereas all decidua and normal endometrium did not show any
      methylation. Allele-specific methylation analysis revealed that this methylation
      was monoallelic. Furthermore, comparison with maternal DNA indicated that APC and
      WIF1 were methylated on the maternal allele, whereas SFRP2 was methylated on the
      paternal allele. Sequence analysis of WIF1 mRNA revealed that only the
      unmethylated paternal allele was transcribed. The imprinting status of these TSGs
      is conserved during pregnancy. These results indicate that TSG imprinting is pre
      existent in normal human placenta and should not be confused with carcinogenesis
      or pathology-induced methylation.

PMID- 19106646
TI  - Cascade transcription of mRNA-type long non-coding RNAs (mlonRNAs) and local
      chromatin remodeling.
AB  - Eukaryotic transcriptome analyses have revealed the presence of a huge number of
      mRNA-type non-coding RNAs (ncRNAs). Expression of them is often developmentally
      regulated, but little is known about their function. We have recently
      demonstrated that cascade of RNA polymerase II (RNAPII)-mediated transcription
      initiation of such mRNA-type long ncRNAs (mlonRNA) results in stepwise disruption
      of local chromatin structure at the fission yeast Schizosaccharomyces pombe
      fbp1(+) locus during transcriptional activation upon glucose derepression.
      Similar transition of RNA transcripts coupled with local chromatin alteration is
      observed meiotically in the fission yeast recombination hotspot ade6-M26. Here,
      we hypothesize that RNAPII transcription of mlonRNAs disrupts chromatin array.
      This idea may provide a new clue to understand why so many species of ncRNAs are
      expressed in eukaryotic cells.

PMID- 19106649
TI  - Dose-intense treatment of mantle cell lymphoma: can durable remission be
      achieved?
AB  - PURPOSE OF REVIEW: Mantle cell lymphoma is a distinct subtype of malignant
      lymphoma, which displays an aggressive clinical course with a continuous relapse
      pattern and the worst long-term outcome of all B-cell lymphoma. Conventional
      dosed chemotherapy achieves only temporary responses with a median duration of
      remissions of only 1-2 years. RECENT FINDINGS: Addition of monoclonal antibodies
      has improved initial response but duration of response remained almost
      uninfluenced. In contrast, dose-intensified regimens including addition of high
      dose Ara-C or myeloablative consolidation achieved significantly improved
      progression-free survival rates whereas the improvement of overall survival has
      not yet been definitely proven by recent multicenter trials. Various phase II
      studies suggest that further intensification (HyperCVAD followed by autologous
      stem cell transplantation) may be beneficial if tolerated. However, potentially
      improved efficacy has to be balanced against increased toxicity and feasibility
      of this approach. SUMMARY: Dose-intensified approaches, either cyclophosphamide,
      hydroxydaunorubicin (adriamycin), oncovin (vincristine), and prednisone (CHOP) +/
      high-dose Ara-C followed by autologous stem cell transplantation or HyperCVAD
      with the addition of rituximab remain the current standard approach in younger
      patients up to 65 years. Future strategies will focus in a slightly different
      direction, namely to integrate the increasing number of molecular targeted
      compounds (proteasome inhibitors, mammalian target of rapamycin antagonists or
      immunomodulatory drugs like lenalidomide) into multimodal approaches to overcome
      the still disappointing long-term prognosis of mantle cell lymphoma.

PMID- 19106650
TI  - To protect and defend: central nervous system prophylaxis in patients with non
      Hodgkin's lymphoma.
AB  - PURPOSE OF REVIEW: Despite remarkable advances in the treatment of non-Hodgkin's
      lymphoma of all histologic subtypes, nervous system involvement remains a dire
      complication associated with a rapid decline in quality of life, few good
      treatment options, and a short overall survival. In fact, these advances in
      treatment may be fueling an increase in the frequency of nervous system relapse.
      A better understanding of the epidemiology, diagnostic techniques, and options
      for prophylaxis of the central nervous system may be one of the best strategies
      for improving the outcome in patients with non-Hodgkin's lymphoma. RECENT
      FINDINGS: Central nervous system relapse in patients with non-Hodgkin's lymphoma
      is, typically, an early event, occurs in the setting of well described
      histologic, demographic, and clinical risk factors, and is characterized
      primarily by the involvement of the cerebrospinal fluid. Cerebrospinal fluid
      prophylaxis in high-risk patients appears to be effective in reducing the
      frequency of this complication. SUMMARY: More aggressive attention to diagnosis,
      focused on cytologic and flow cytometric evaluation of the cerebrospinal fluid in
      high-risk patients, will identify more patients with early and potentially more
      treatable central nervous system lymphoma. Cerebrospinal fluid prophylaxis
      appears to reduce the frequency of this complication in high-risk populations,
      but controversy remains regarding the most important high-risk characteristics
      and the optimum prophylactic interventions.

PMID- 19106647
TI  - MicroRNA miR-155 is a biomarker of early pancreatic neoplasia.
AB  - BACKGROUND: Intraductal papillary mucinous neoplasms (IPMNs) are non-invasive
      precursor lesions of pancreatic cancer. Misexpression of microRNAs (miRNAs) is
      commonly observed in pancreatic adenocarcinoma. In contrast, miRNA abnormalities
      in pancreatic cancer precursor lesions have not been documented. EXPERIMENTAL
      DESIGN: Relative expression levels of a panel of twelve miRNAs upregulated in
      pancreatic cancers were assessed in 15 non-invasive IPMNs, using quantitative
      reverse transcription PCR (qRT-PCR). Two significantly overexpressed miRNAs-miR
      155 and miR-21-were evaluated by locked nucleic acid in situ hybridization (LNA
      ISH) in a panel of 64 archival IPMNs. The expression of miR-155 and miR-21 was
      also evaluated in pancreatic juice samples obtained from ten patients with
      surgically resected IPMNs and five patients with non-neoplastic pancreato-biliary
      disorders ("disease controls"). RESULTS: Significant overexpression by qRT-PCR of
      ten of the twelve miRNAs was observed in the 15 IPMNs versus matched controls (p
      < 0.05), with miR-155 (mean 11.6-fold) and miR-21 (mean 12.1-fold) demonstrating
      highest relative fold-changes in the precursor lesions. LNA-ISH confirmed the
      expression of miR-155 in 53 of 64 (83%) IPMNs compared to 4 of 54 (7%) normal
      ducts, and of miR-21 in 52 of 64 (81%) IPMNs compared to 1 of 54 (2%) normal
      ducts, respectively (p < 0.0001). Upregulation of miR-155 transcripts by qRT-PCR
      was observed in 6 of 10 (60%) IPMN-associated pancreatic juice samples compared
      to 0 of 5 (0%) disease controls. CONCLUSIONS: Aberrant miRNA expression is an
      early event in the multistage progression of pancreatic cancer, and miR-155
      warrants further evaluation as a biomarker for IPMNs in clinical samples.

PMID- 19106651
TI  - Follicular non-Hodgkin lymphoma: long-term results of stem-cell transplantation.
AB  - PURPOSE OF REVIEW: Hematopoietic stem-cell transplantation is an effective
      treatment option for follicular lymphoma. This review summarizes recent updates
      of the literature focusing on the available long-term follow-up of high-dose
      therapeutic approaches. RECENT FINDINGS: Autologous transplantation can prolong
      overall survival in relapsed disease and can extend progression-free survival in
      first remission. With more than 10 years of follow-up, the survival curves
      demonstrate a plateau indicating a potential cure in certain patients. Use of
      allogeneic transplantation may result in cure as well, but has been plagued by
      high treatment-related mortality rates when myeloablative conditioning is used.
      The decreased toxicity of reduced-intensity conditioning is more applicable to
      the older follicular lymphoma population, but long-term follow-up data are
      lacking. SUMMARY: For selected patients, both autologous and allogeneic
      transplantation offer the possibility of prolonged survival and can result in a
      cure in up to 25-45% of cases. It is unclear whether to incorporate monoclonal
      antibody or radioimmunoconjugate therapy. Stem-cell transplantation should at
      least be considered in patients younger than 60 years, possibly early in the
      disease course. Late consequences such as an increased risk of second malignancy
      may compromise this approach and close patient follow-up is essential.

PMID- 19106652
TI  - PET scanning and prognosis in Hodgkin's lymphoma.
AB  - PURPOSE OF REVIEW: Risk-adapted treatment strategies are currently under
      investigation in the management of patients with lymphoma. This review presents
      the latest evidence for the use of early interim [(18)F]-fluorodeoxyglucose
      positron emission tomography for risk-adapted treatment in Hodgkin's lymphoma.
      RECENT FINDINGS: In recent years, PET after two cycles of ABVD (adriamycin,
      bleomycin, vincristin, and dexamethasone) was shown to be the only independent
      prognostic factor for the prediction of relapse in Hodgkin's lymphoma and to have
      at least the same prognostic accuracy as end-of-treatment PET. A high prognostic
      value of PET was reported even earlier, before the second cycle of chemotherapy.
      The earlier PET becomes negative, the more chemosensitive the disease, which may
      offer opportunities toward the limitation of the therapy. However, more false
      positive lesions occur at earlier time points, and preliminary results indicate
      that accuracy of PET results differs after BEACOPP (bleomycin, etoposide,
      doxorubicin, cyclophosphamide, vincristine, procarbazine, and prednisone) and
      immunotherapy. SUMMARY: [(18)F]-Fluorodeoxyglucose-positron emission tomography
      after two cycles of ABVD is now recognized as the single most important factor in
      defining disease-specific outcome and is highly promising for investigation of
      response-adapted treatment strategies. It is now recognized that the optimal time
      point of PET for response evaluation is crucial and dependent on the administered
      treatment. Standardization of PET-response is essential and should be adapted to
      time-dependent and therapy-dependent changes.

PMID- 19106653
TI  - Malignancies in HIV: the Indian scenario.
AB  - PURPOSE OF REVIEW: India has the second largest number of HIV/AIDS patients in
      the world; however, studies done in the area of HIV-related malignancies are few.
      With the availability of highly active antiretroviral therapy and treatment and
      prevention of opportunistic infections, an increase in life expectancy of HIV
      infected individuals and an increase in HIV-related malignancies is expected. The
      purpose of this review is to put forth the Indian scenario of HIV-related
      malignancies. RECENT FINDINGS: About 2.5 million Indians have HIV/AIDS. Non
      Hodgkin's lymphoma and cervical cancer were found to occur in a higher proportion
      among the HIV-infected individuals in India as compared with non-HIV-infected
      individuals. The incidence of AIDS-related primary central nervous system
      lymphoma is low in India. Kaposi's sarcoma is rare in India. Amongst the non-AIDS
      defining cancers anal cancer, testicular cancer, Hodgkin's disease, colon cancer
      and certain head and neck cancer sites in men and vaginal cancers among women
      were found to occur more frequently. SUMMARY: With the availability of highly
      active antiretroviral therapy an increased mortality and morbidity due to
      neoplastic diseases is expected in the future. As India is a large country and
      geographically and culturally diverse, large-scale studies need to be done
      linking the regional cancer centres with the AIDS centres across the country to
      evaluate the exact burden of HIV-related malignancies.

PMID- 19106654
TI  - Management of AIDS-related lymphoma.
AB  - PURPOSE OF REVIEW: With the advent of highly active antiretroviral therapy, the
      epidemiology of AIDS-lymphoma has changed, and prognosis has improved. Paradigms
      of therapy have changed. Although the incidence of AIDS-lymphoma has decreased,
      the incidence of HIV-associated Hodgkin's lymphoma has increased; mechanisms for
      these changes in epidemiology will be discussed. RECENT FINDINGS: Use of highly
      active antiretroviral therapy, either concomitantly or immediately after
      completion of chemotherapy, has resulted in rates of complete remission and
      survival that are similar to those in HIV-negative patients. The use of
      rituximab, while initially controversial because of reports of increased risk of
      infectious death, is associated with improved outcome; the increased risk of
      infectious death has not been confirmed. The infusional etoposide, prednisone,
      vincristine, cyclophosphamide, doxorubicin regimen is associated with excellent
      results. High-dose chemotherapy with autologous stem cell transplant is
      associated with long-term, disease-free survival in approximately 50-80% of
      patients with relapsed/refractory AIDS-lymphoma. SUMMARY: Highly active
      antiretroviral therapy should be used with chemotherapy. Addition of rituximab is
      associated with improved response rates, without an increase in infections.
      Infusional etoposide, prednisone, vincristine, cyclophosphamide, doxorubicin is
      associated with excellent results among patients with either diffuse large B cell
      lymphoma or Burkitt's lymphoma. Optimal therapy for patients with HIV-Hodgkin's
      lymphoma has not yet been defined.

PMID- 19106655
TI  - Smoke and mirrors: HIV-related lung cancer.
AB  - PURPOSE OF REVIEW: The introduction of highly active antiretroviral therapy has
      dramatically reduced AIDS-related illnesses and increased life expectancy for
      people living with HIV infection. At the same time, non-AIDS-defining cancers are
      becoming an increasing problem and now account for a large proportion of HIV
      related deaths. Perhaps the most important and controversial of these is HIV
      related lung cancer. There are a number of unresolved issues surrounding this
      illness, which are the subject of this review. RECENT FINDINGS: Smoking does not
      account for all of the increase in the incidence of lung cancer seen in HIV
      patients. Other factors accounting for the increased incidence remain undefined.
      Highly active antiretroviral therapy may not have had a beneficial effect on
      either the incidence or outcome of the disease, which needs further
      investigation. Early diagnosis and offering these patients potentially curative
      therapy wherever appropriate is of utmost importance. SUMMARY: HIV-related lung
      cancer is becoming an increasingly important problem as patients are living
      longer with HIV infection.

PMID- 19106656
TI  - Evolving epidemiology of malignancies in HIV.
AB  - PURPOSE OF REVIEW: Morbidity and mortality related to malignancy are increasing
      in HIV-infected patients. We aim at reviewing the literature on recent changes in
      the incidence of AIDS-defining and non-AIDS-defining malignancies and the
      specific characteristics of the main cancers emerging in HIV-infected patients.
      RECENT FINDINGS: Currently, malignancies are the most frequent underlying cause
      of death (around one-third) of HIV-infected patients. Since the introduction of
      combination antiretroviral therapy, the incidence of Kaposi's sarcoma and
      cerebral lymphoma (among AIDS-defining cancers) decreased in parallel with AIDS
      defining infections, whereas the incidence of systemic non-Hodgkin's lymphoma and
      cervical cancer decreased less than others and remains higher in HIV-infected
      patients than in the general population. The most recent and large studies have
      also shown a 1.7-3-fold higher risk of developing non-AIDS malignancies in HIV
      infected patients as compared with the general population without a significant
      impact of combination antiretroviral therapy on these trends. These malignancies
      include Hodgkin's disease, lung, anal, head and neck cancers, hemopathies, and
      conjunctival cancers. In addition, the poorer prognosis reported in HIV-infected
      patients affected by malignancies might be interpreted as a consequence of late
      screening or immunosuppression. SUMMARY: Prevention and screening management
      procedures need to be assessed on the basis of specific evidence-based studies in
      the HIV-infected population. Interventions, known to be efficacious in other
      populations, should systematically be used or adapted if necessary (alcohol and
      tobacco cessation programs and viral coinfection management). The respective role
      of HIV itself, immunosuppression, and antiretrovirals as pro-oncogenic factors
      need to be further examined.

PMID- 19106657
TI  - Human papillomavirus-related diseases in HIV-infected individuals.
AB  - PURPOSE OF REVIEW: To present recent publications in human papillomavirus
      associated diseases and their relationship to HIV-infected patients. RECENT
      FINDINGS: Studies assessing geographic variations in human papillomavirus types
      and prevalence in cervical dysplasia and cancer in HIV-infected women suggest
      that although human papillomavirus types 16 and 18 dominate, multiple other human
      papillomavirus types may play a role in carcinogenesis. Anal dysplasia and cancer
      incidence continues to rise in the highly active antiretroviral therapy era;
      however, data on outcomes following therapy for anal dysplasia (infrared
      coagulator, high-resolution anoscopy-guided ablation) and anal cancer
      (chemoradiation and possibly intensity-modulated radiation therapy) have been
      encouraging. Oral human papillomavirus may be associated with lower genital tract
      human papillomavirus infection and may have implications in the development of
      oropharyngeal cancer. SUMMARY: As HIV-infected patients in the highly active
      antiretroviral therapy era continue to have high rates of cervical and anal
      cancer, it is important to continue screening efforts and treatment of
      preinvasive disease. Treatment options for anal dysplasia and anal cancer in HIV
      infected individuals are expanding and may lead to decreased morbidity and
      mortality. Trials assessing safety and immunogenicity of the human papillomavirus
      quadrivalent vaccine in people with HIV have started enrollment, and if
      successful, may prevent many human papillomavirus-associated cancers.

PMID- 19106658
TI  - Gynaecological oncology.

PMID- 19106659
TI  - Hormone therapy for epithelial ovarian cancer.
AB  - PURPOSE OF REVIEW: Hormonal therapy has been used erratically to treat epithelial
      ovarian cancer since the mid 1960s; however, there has been little progress until
      recently in our understanding of which patients might benefit from treatment.
      Some clarity in the field is now beginning to emerge from recent studies, which
      have started to define biomarkers within epithelial ovarian cancers that link
      with hormonal response and thereby indicate which cohort of patients might be
      amenable to hormonal treatment. RECENT FINDINGS: Oestrogen-deprivation therapy in
      the form of the aromatase inhibitor letrozole has demonstrated activity in three
      clinical studies. As only a minority of patients will benefit from hormonal
      approaches, recent efforts have focussed on the use of molecular markers to help
      identify which subgroup of patients might respond to treatment. Parallel
      laboratory studies using primary cancer material for which endocrine response is
      known and model-based findings have identified components of oestrogen signalling
      pathways that may help predict outcome. SUMMARY: Use of the antioestrogen
      letrozole in ovarian cancer has consistently demonstrated a significant level of
      activity and the larger clinical studies have linked response with oestrogen
      receptor alpha expression and other biomarkers.

PMID- 19106660
TI  - Molecule-targeted agents in endometrial cancer.
AB  - PURPOSE OF REVIEW: Endometrial cancer is the most common gynaecological
      malignancy for which platinum-based and anthracycline-based combinations,
      with/without taxanes, are the most active but toxic treatments. The preliminary
      results achieved with two molecule-targeted agents suggest that a better
      knowledge in molecular biology of this neoplasm might improve the clinical
      outcome. RECENT FINDINGS: Two major types (type I and type II) of endometrial
      cancer are known with specific features and different changes in the genetic
      setting. Mutation of phosphatase and tensin homologue deleted on chromosome 10,
      leading to hyperactivation of the mammalian target of rapamycin pathway, is a
      common alteration in type I, whereas human epidermal growth factor receptor 2/neu
      overexpression, with increased tumour proliferation, is frequent in type II.These
      alterations provide the rationale for molecule-targeted treatments. Phase II
      studies have been performed with the three major rapamycin analogue mammalian
      target of rapamycin inhibitors in recurrent or advanced endometrial cancer with
      promising results. Hyperexpression of human epidermal growth factor receptor
      2/neu in endometrial cancer justifies clinical evaluation of trastuzumab, the
      humanized antihuman epidermal growth factor receptor 2/neu monoclonal antibody.
      SUMMARY: As with other targeted therapies, antitumour activity as single agent is
      limited but there is clear pharmacological indication for the evaluation of
      combination regimens, based on preclinical and clinical data. The identification
      of biomarkers of biological effects might help in the selection of potential
      responders.

PMID- 19106661
TI  - Management of granulosa cell tumour of the ovary.
AB  - PURPOSE OF REVIEW: Granulosa cell tumours of the ovary are relatively uncommon
      malignant tumours. Although the majority of patients present with early-stage
      disease that is curable, approximately 80% of patients with advanced tumours die
      from recurrent disease. The purpose of this review is to provide the clinician
      with an update on recent research relevant to granulosa cell tumours. RECENT
      FINDINGS: The measurement of serum inhibin levels is useful in the diagnosis of
      granulosa cell tumours in postmenopausal women and for monitoring the disease
      following oophorectomy at any age. Surgery remains the most effective primary
      treatment, whereas hormonal therapy for patients with advanced stages or
      recurrent disease has resulted in varying outcomes. The presence of the gsp
      oncogene and high GATA-4 protein expression in juvenile granulosa cell tumours
      may provide new prognostic markers. In-vitro testing of a recently discovered
      tyrosine kinase inhibitor indicates that further developments in this area may
      provide a novel therapeutic target for the treatment of granulosa cell tumours.
      SUMMARY: Further investigation to determine the molecular changes that contribute
      to tumorigenesis in granulosa cells is required. Understanding the molecular
      pathogenesis of this disease will potentially provide novel targeted therapeutic
      options which will improve the survival rate of these patients.

PMID- 19106662
TI  - Management of melanomas of the female genital tract.
AB  - PURPOSE OF REVIEW: The significant increase in cutaneous melanomas over the past
      30 years has led to studies resulting in advances in their diagnosis, staging,
      surgical treatment, and adjuvant therapies. Similar approaches have been
      investigated in patients with far rarer malignant melanomas of the female genital
      tract. This review will summarize the current state of knowledge on the
      incidence, causes, presenting symptoms, prognostic factors, therapeutic
      approaches, and outcomes, site-by-site, for primary melanomas of the vulva,
      vagina, urethra, ovary, and the uterine cervix. RECENT FINDINGS: Surgery remains
      the initial treatment of choice for localized melanomas of the female genital
      tract, with less radical, organ function preserving resections demonstrating
      similar control rates compared with more radical surgical approaches in vulva and
      possibly vaginal melanomas. Radiation therapy may play a role in the treatment of
      patients with close resection margins, regional nodal metastasis, or unresectable
      tumors. Sentinel lymph node studies, positron emission tomography and computed
      tomography scans for staging and evaluation of response, and adjuvant chemo or
      biochemotherapy warrant further investigation. SUMMARY: The results of treatment
      for female genital tract melanomas remain poor. Although surgery remains the
      initial treatment of choice for localized disease, adjuvant local-regional, and
      systemic therapies are needed.

PMID- 19106663
TI  - Vaccines against cervical cancer.
AB  - PURPOSE OF REVIEW: The purpose of this review is to give an overview of recent
      developments relating to human papillomavirus vaccines and their effect on
      cervical cancer. Original research publications from the last year (2007) have
      been reviewed and summarized to present an up to date synopsis of relevant
      trials, and the impact they will have on clinical practice. Comparisons of the
      two vaccines on the market are made, and details of each are given. The effect of
      vaccination on men and those in the developing world is explored. RECENT
      FINDINGS: Recent findings include results of the Females United to Unilaterally
      Reduce Endo/Ectocervical Disease II (FUTURE II) and PApilloma TRIal against
      Cancer In young Adults (PATRICIA) trials that show a significant reduction in
      human papillomavirus-associated anogenital disease with both quadrivalent and
      bivalent vaccines. The effect is greatest in women who are not yet exposed to the
      human papillomavirus. The international community recognizes the potential impact
      of this, particularly in the developing world, and strategies are being developed
      to try and deliver care effectively. SUMMARY: In summary, research published in
      the last year has continued the initial optimistic outlook for human
      papillomavirus vaccination and it is likely that its effect on cervical cancer
      will be as promising as initially appeared.

PMID- 19106664
TI  - Fertility preserving surgery for carcinoma of the cervix.
AB  - PURPOSE OF REVIEW: Cervical cancer remains the second most common female
      malignancy. Screening programmes have reduced the overall incidence,
      predominantly in the western world; however, this has led to a disproportionate
      rise in the incidence of early-stage disease, with a related increase in demand,
      for fertility-sparing techniques to be developed. RECENT FINDINGS: Standard
      treatment for cervical cancer compromises fertility. A radical wide local
      excision of carefully selected early-stage tumours will allow conservation of the
      body of the uterus with a vaginoisthmic anastomosis enabling continuity of the
      vagina to be preserved following insertion of an isthmic cerclage suture. Pelvic
      node dissection may be performed at the same time by laparoscopic techniques.
      Over 900 cases have been performed and reported in the literature worldwide. Most
      have been carried out vaginally (radical vaginal trachelectomy and laparoscopic
      pelvic node dissection). A smaller number have been performed abdominally. There
      have been over 300 pregnancies reported with 196 live births. There has been a
      10% significant prematurity rate with birth prior to 32 weeks. There have been 31
      recurrences (4%), and 16 deaths (2%). SUMMARY: Radical vaginal trachelectomy
      appears safe when performed in centres with appropriate experience of radical
      vaginal surgery and laparoscopic techniques. The impact of this new approach
      questions traditional teaching, thus preserving potential fertility in up until
      now impossible circumstances.

PMID- 19106666
TI  - Bibliography. Current World Literature.

PMID- 19106665
TI  - Robotic assistance in gynecological oncology.
AB  - PURPOSE OF REVIEW: The da Vinci robot has proved to be the most advanced surgical
      system in gynecology. In this review we evaluated the possibilities of applying
      robotic assistance to improve gynecological endoscopic oncological surgery.
      RECENT FINDINGS: A literature survey on robotic-assisted gynecological oncology
      clearly supports the use of the da Vinci surgical system in laparoscopic
      oncological surgery. Robotic precision in tumor excision, easier intracorporal
      suturing and favorable ergonomics for the surgeon make the da Vinci robot
      particularly suitable for performing complex laparoscopic microinvasive surgical
      operations in gynecological oncology. SUMMARY: Robotic surgery combines the
      advantages of open surgery and endoscopic surgery. In our opinion, robotic
      surgery may lead to better results than conventional laparoscopic surgery,
      particularly in the field of gynecological oncology. However, this opinion has
      yet to be confirmed by randomized studies.

PMID- 19106667
TI  - Survival with emergency tourniquet use to stop bleeding in major limb trauma.
AB  - OBJECTIVE: The purpose of this study was to determine if emergency tourniquet use
      saved lives. SUMMARY BACKGROUND DATA: Tourniquets have been proposed as
      lifesaving devices in the current war and are now issued to all soldiers. Few
      studies, however, describe their actual use in combat casualties. METHODS: A
      prospective survey of injured who required tourniquets was performed over 7
      months in 2006 (NCT00517166 at ClinicalTrials.gov). Follow-up averaged 28 days.
      The study was at a combat support hospital in Baghdad. Among 2,838 injured and
      admitted civilian and military casualties with major limb trauma, 232 (8%) had
      428 tourniquets applied on 309 injured limbs. We looked at emergency tourniquet
      use, and casualties were evaluated for shock (weak or absent radial pulse) and
      prehospital versus emergency department (ED) tourniquet use. We also looked at
      those casualties indicated for tourniquets but had none used. We assessed
      survival rates and limb outcome. RESULTS: There were 31 deaths (13%). Tourniquet
      use when shock was absent was strongly associated with survival (90% vs. 10%; P <
      0.001). Prehospital tourniquets were applied in 194 patients of which 22 died
      (11% mortality), whereas 38 patients had ED application of which 9 died (24%
      mortality; P = 0.05). The 5 casualties indicated for tourniquets but had none
      used had a survival rate of 0% versus 87% for those casualties with tourniquets
      used (P < 0.001). Four patients (1.7%) sustained transient nerve palsy at the
      level of the tourniquet. No amputations resulted solely from tourniquet use.
      CONCLUSIONS: Tourniquet use when shock was absent was strongly associated with
      saved lives, and prehospital use was also strongly associated with lifesaving. No
      limbs were lost due to tourniquet use. Education and fielding of prehospital
      tourniquets in the military environment should continue.

PMID- 19106668
TI  - Tourniquets: another adjunct in damage control?

PMID- 19106669
TI  - The effects of trauma center care, admission volume, and surgical volume on
      paralysis after traumatic spinal cord injury.
AB  - OBJECTIVE: To evaluate compliance with American College of Surgeons (ACS)
      guidelines and whether trauma center designation, hospital traumatic spinal cord
      injury (TSCI) case volume or spinal surgery volume is associated with paralysis.
      We hypothesized a priori that trauma center care, by contrast to nontrauma center
      care, is associated with reduced paralysis at discharge. SUMMARY BACKGROUND DATA:
      Approximately 11,000 persons incur a TSCI in the United States annually. The ACS
      recommends all TSCI patients be taken to a level I or II trauma center. METHODS:
      We studied 4121 patients diagnosed with TSCI by ICD-9-CM criteria in the 2001
      hospital discharge files of 7 states (Florida, Massachusetts, New Jersey, New
      York, Texas, Virginia, Washington), who were treated in 100 trauma centers and
      601 nontrauma centers. We performed multivariate analyses, including a propensity
      score quintile approach, adjusting for differences in case mix and clustering by
      hospital and by state. We also studied 3125 patients using the expanded modified
      Medicare Provider Analysis and Review records for the years 1996, 2001, and 2006
      to assess temporal trends in paralysis by trauma center designation. RESULTS:
      Mortality was 7.5%, and 16.3% were discharged with paralysis. Only 57.9% (n =
      2378) received care at a designated trauma center. Trauma centers had a 16-fold
      higher admission caseload (20.7 vs. 1.3; P < 0.001) and 30-fold higher surgical
      volume (9.6 vs. 0.3; P < 0.001). In the multivariate propensity analysis,
      paralysis was significantly lower at trauma centers (adjusted odds ratio 0.67;
      95% confidence interval, 0.53-0.85; P = 0.001). Higher surgical volume, not
      higher admission volume, was associated with lower risk of paralysis. Indeed, at
      nontrauma centers, higher admission caseload was associated with worse outcome.
      There was no significant difference in mortality. CONCLUSIONS: Trauma center care
      is associated with reduced paralysis after TSCI, possibly because of greater use
      of spinal surgery. National guidelines to triage all such patients to trauma
      centers are followed little more than half the time.

PMID- 19106670
TI  - The message is clear: patients with spinal column injury should be treated at a
      trauma center to decrease the likelihood of long-term paralysis.

PMID- 19106671
TI  - The current role of radiofrequency ablation in the management of hepatocellular
      carcinoma: a systematic review.
AB  - OBJECTIVE: To review the current status of radiofrequency ablation (RFA) in the
      management of hepatocellular carcinoma (HCC). SUMMARY BACKGROUND DATA: The
      development of local ablative therapy has been 1 of the major advances in the
      treatment of HCC. Its role in the management of HCC is still rapidly evolving.
      METHODS: Studies were identified by searching Medline, and PubMed databases for
      articles from January 1997 to April 2008 using the keywords "radiofrequency
      ablation," "hepatocellular carcinoma" and "ablation of HCC." Additional papers
      were identified by a manual search of the references from the key articles.
      Randomized controlled trials, nonrandomized comparative studies, cohort studies,
      were reviewed. Cohort studies with follow-up of less than 12 months and case
      reports were excluded. RESULTS: Five aspects of RFA were analyzed: (1) RFA in
      comparison with other local ablative therapies; (2) RFA for unresectable HCC; (3)
      RFA as bridging therapy before liver transplantation; (4) RFA as primary
      treatment for resectable HCC; and (5) RFA for recurrent HCC after partial
      hepatectomy. Ten RCTs, 8 nonrandomized controlled trials and 26 cohort studies
      were included in this analysis. CONCLUSIONS: The evidence in the medical
      literature showed RFA was more effective than other local ablative therapies, and
      supported its use in the treatment of unresectable small HCC, recurrent small
      HCC, and as bridging therapy before liver transplantation, and as a primary
      treatment in competition with partial hepatectomy for resectable small HCC.

PMID- 19106672
TI  - Total skin-sparing mastectomy: complications and local recurrence rates in 2
      cohorts of patients.
AB  - PURPOSE: Dissemination of the total skin-sparing mastectomy (TSSM) technique is
      limited by concerns of nipple viability, flap necrosis, local recurrence risk,
      and the technical challenge of this procedure. We sought to define the impact of
      surgical and reconstructive variables on complication rates and assess how
      changes in technique affect outcomes. PATIENTS AND METHODS: We compared the
      outcomes of TSSM in 2 cohorts of patients. Cohort 1: the first 64 TSSM procedures
      performed at our institution, between 2001 and 2005. Cohort 2: 106 TSSM performed
      between 2005 and 2007. Outcomes of cohort 1 were analyzed in 2005. At that time,
      potential risk factors for complications were identified, and efforts to minimize
      these risks by altering operative and reconstructive technique were then applied
      to patients in cohort 2. The impact of these changes on outcomes was assessed.
      Logistic regression was used to determine the association between predictor
      variables and adverse outcomes (Stata 10). RESULTS: The predominant incision type
      in cohort 2 involved less than a third of the nipple areola complex (NAC), and
      the most frequent reconstruction technique was tissue expander placement. Between
      cohort 1 and cohort 2, nipple survival rates rose from 80% to 95% (P = 0.003) and
      complication rates declined: necrotic complications (30% --> 13%; P = 0.01),
      implant loss (31% --> 10%; P = 0.005), skin flap necrosis (16%-11%; not
      significant), and significant infections (17%-9%, not significant). Incisions
      involving >30% of the NAC (P < 0.001) and reconstruction with autologous tissue
      (P < 0.001) were independent risk factors for necrotic complications. The local
      recurrence rate was 0.6% at a median follow-up of 13 months (range, 1-65), with
      no recurrences in the NAC. CONCLUSION: Focused improvement in technique has
      resulted in the development of TSSM as a successful intervention at our
      institution that is oncologically safe with high nipple viability and early low
      rates of recurrence. Identifying factors that contribute to complications and
      changing surgical and reconstructive techniques to eliminate risk factors has
      greatly improved outcomes.

PMID- 19106673
TI  - Low recurrence rate after laparoscopic (TEP) and open (Lichtenstein) inguinal
      hernia repair: a randomized, multicenter trial with 5-year follow-up.
AB  - OBJECTIVES: To compare a laparoscopic (totally extraperitoneal patch (TEP)) and
      an open technique (Lichtenstein) for inguinal hernia repair regarding recurrence
      rate and possible risk factors for recurrence. SUMMARY BACKGROUND DATA:
      Laparoscopic hernia repair has been introduced as an alternative to open repair.
      Short-term follow-up suggests benefits for those patients operated with a
      laparoscopic approach compared with open techniques; ie, less postoperative pain
      and a shorter convalescence period. Long-term results, however, are less well
      known. METHODS: The study was conducted as a multicenter randomized trial with a
      5-year follow-up. A total of 1512 men aged 30 to 70 years, with a primary
      unilateral inguinal hernia, were randomized to either TEP or Lichtenstein repair.
      RESULTS: Overall, 665 patients in the TEP group and 705 patients in the
      Lichtenstein group were evaluable. The cumulative recurrence rate was 3.5% in the
      TEP group and 1.2% in the Lichtenstein group (P = 0.008). Test for heterogeneity
      revealed significant differences between individual surgeons. The exclusion of 1
      surgeon, who was responsible for 33% (7 of 21) of all recurrences in the TEP
      group, lowered the cumulative recurrence rate to 2.4% in this group, which was
      not statistically different from that of the Lichtenstein group. CONCLUSIONS: The
      recurrence rate for both TEP and Lichtenstein repair was low. A higher cumulative
      recurrence rate in the TEP group was seen at 5 years. Further analysis revealed
      that this could be attributable to incorrect surgical technique.

PMID- 19106674
TI  - Laparoscopic sigmoid resection for diverticulitis decreases major morbidity
      rates: a randomized control trial: short-term results of the Sigma Trial.
AB  - BACKGROUND: No randomized controlled trial has compared laparoscopic sigmoid
      resection (LSR) to open sigmoid resection (OSR) for symptomatic diverticulitis of
      the sigmoid colon. This study tested the hypothesis that LSR is associated with
      decreased postoperative complication rates as compared with OSR. METHODS: This
      was a prospective, multicenter, double-blind, parallel-arm, randomized controlled
      trial. Eligible patients were randomized to either LSR or OSR. Endpoints included
      postoperative mortality, and complications were classified as major and minor.
      The generator of the allocation sequence was separated from the executor.
      Blinding was ensured using an opaque wound dressing to cover the abdomen.
      Symptomatic diverticulitis of the sigmoid colon was defined as recurrent disease
      Hinchey I, IIa, IIb, symptomatic stricture, or severe rectal bleeding. The
      decision to discharge patients was made by independent physicians blind to the
      allocation sequence. Data were analyzed according to the intention to treat
      principle. RESULTS: From 2002 to 2006, 104 patients were randomized in 5 centers.
      All patients underwent the allocated intervention. Fifty-two LSR patients were
      comparable to 52 OSR patients for gender, age, BMI, ASA grade, comorbid
      conditions, previous abdominal surgery, and indication for surgery. LSR took
      longer (P = 0.0001) but caused less blood loss (P = 0.033). Conversion rate was
      19.2%. Mortality rate was 1%. There were significantly more major complications
      in OSR patients (9.6% vs. 25.0%; P = 0.038). Minor complication rates were
      similar (LSR 36.5% vs. OSR 38.5%; P = 0.839). LSR patients had less pain (Visual
      Analog Scale 1.6; P = 0.0003), systemic analgesia requirement (P = 0.029), and
      returned home earlier (P = 0.046). The short form-36 questionnaire showed
      significantly better quality of life for LSR. CONCLUSIONS: LSR was associated
      with a 15.4% reduction in major complication rates, less pain, improved quality
      of life, and shorter hospitalization at the cost of a longer operating time.

PMID- 19106675
TI  - Endoscopic and surgical treatments for achalasia: a systematic review and meta
      analysis.
AB  - BACKGROUND: Although rare, esophageal achalasia is the best described primary
      esophageal motility disorder. Commonly used treatments are endoscopic botulin
      toxin injection (EBTI), endoscopic balloon dilation (EBD), and surgical myotomy
      with or without a fundoplication; however, reported outcomes mostly come from
      cohort studies. OBJECTIVE: To summarize and compare the safety and efficacy of
      endoscopic and surgical treatments for esophageal achalasia. METHODS: A
      systematic electronic Medline literature search of articles on esophageal
      achalasia. Treatment options reviewed included EBTI, EBD, and surgical myotomy
      using open and minimally invasive techniques. Main outcome measures were
      frequency of symptom relief, prevalence of post-treatment gastroesophageal reflux
      (GER), and complications. Outcome probability was estimated using weighted
      averages of the sample prevalence in each study, with weights equal to the number
      of patients. Outcomes, within or across studies, were compared using meta
      analysis and meta-regression, respectively. RESULTS: A total of 105 articles
      reporting on 7855 patients were selected, tabulated and reviewed. Symptom relief
      after EBD was better than after EBTI (68.2% vs. 40.6%; OR 3.4; 95% CI, 1.2-9.8; P
      = 0.02), and the need for additional therapy was greater for patients receiving
      EBTI (46.6% vs. 25%; OR, 2.6; 95% CI, 1.05-6.5; P = 0.04). Laparoscopic myotomy,
      when combined with an antireflux procedure, provided better symptom relief (90%)
      than all endoscopic and other surgical approaches and a low complication rate
      (6.3%). The incidence of postoperative GER was lower when a fundoplication was
      added to a laparoscopic myotomy (31.5% without a fundoplication vs. 8.8% with;
      OR, 6.3; 95% CI, 2.0-19.4; P = 0.003). CONCLUSIONS: EBD is superior to EBTI.
      Laparoscopic myotomy with fundoplication was the most effective surgical
      technique and can be considered the operative procedure of choice.

PMID- 19106676
TI  - Sentinel node mapping guided by indocyanine green fluorescence imaging in gastric
      cancer.
AB  - OBJECTIVE: In this study, we determined the possible usefulness of sentinel node
      (SN) mapping guided by indocyanine green (ICG) fluorescence imaging in the
      management of gastric cancer. SUMMARY BACKGROUND DATA: ICG fluorescence imaging
      system has recently been developed for obtaining biochemical information from
      living tissues. METHODS: Our series consisted of 56 patients with gastric cancer
      who underwent standard gastrectomy with lymphadenectomy. Two milliliters of ICG
      solution (0.5%) was injected into the submucosa around the tumor endoscopically
      before the operation or into the subserosa intraoperatively. ICG fluorescence
      imaging was conducted using a charge-coupled device camera with a light-emitting
      diode having a wavelength of 760 nm as the light source and a cut filter to
      filter out light with wavelengths below 820 nm as the detector. RESULTS: SNs were
      detected in 54 (96.4%) of the 56 patients, and the mean number of SNs was 7.2 +/-
      7.0. Even SNs that were not green in color could be easily and clearly visualized
      by ICG fluorescence imaging. cT1-stage cancers were associated with a
      significantly higher accuracy rate (97.2% vs. 72.2%, P = 0.0127) than cT2-or cT3
      stage cancers. Preoperative ICG injection was associated with a significantly
      higher incidence of cT1-stage cancers (87.1% vs. 40.0%, P = 0.0004), a larger
      mean number of SNs (9.9 +/- 7.5 vs. 4.1 +/- 5.0, P < 0.0001), a higher accuracy
      rate (100% vs. 73.9%, P = 0.0039), and a lower false negative rate (0% vs. 60.0%,
      P = 0.0345) as compared with intraoperative ICG injection. CONCLUSIONS: This
      study shows that ICG fluorescence imaging allows highly sensitive image-guided
      intraoperative SN mapping in cases of gastric cancer. Our data suggest that SN
      mapping guided by ICG fluorescence imaging might be useful for predicting the
      metastatic status in lymph nodes in cases of gastric cancer, especially those
      with cT1-stage cancer.

PMID- 19106677
TI  - Small bowel cancer in the United States: changes in epidemiology, treatment, and
      survival over the last 20 years.
AB  - BACKGROUND: Previous studies have shown an increasing incidence of small bowel
      tumors in the United States. Our objective was to assess this increase by
      examining changes in histology-specific incidence, treatment, and survival.
      METHODS: Patients with small bowel malignancies were identified from the National
      Cancer Data Base (NCDB, 1985-2005) and the Surveillance Epidemiology and End
      Results (SEER, 1973-2004) database. Age-adjusted incidence rates were calculated
      using SEER. Treatment and survival trends over time were examined using the
      National Cancer Data Base. Regression models were developed to assess survival
      over time. RESULTS: Sixty-seven thousand eight hundred forty-three patients were
      identified with small bowel malignancies: 37.4% carcinoid, 36.9% adenocarcinomas,
      8.4% stromal tumors, and 17.3% lymphomas. From 1973 to 2004, the incidence of
      carcinoid tumors increased more than 4-fold (2.1 to 9.3 per million), whereas
      changes in adenocarcinomas, stromal tumors, and lymphomas were less pronounced.
      From 1985 to 2005, utilization of surgery increased significantly for carcinoid
      tumors from 78.8% to 87.4% (P < 0.0001). Adjuvant chemotherapy utilization for
      adenocarcinoma increased from 8.1% in 1985 to 23.8% in 2005 (P < 0.0001).
      Treatment over time was generally unchanged for lymphoma and stromal tumors. Five
      year survival after resection remained unchanged over time for all histologic
      subtypes even after adjusting for changes in patient demographics, tumor
      characteristics, and treatment approaches. CONCLUSIONS: The overall incidence of
      small intestine malignancies has increased considerably, primarily because of
      carcinoid tumors which are now the most common small bowel cancer. With current
      treatments, survival has remained relatively unchanged over the last 20 years.
      Novel therapeutic options need to be investigated.

PMID- 19106678
TI  - Effect of surgically induced weight loss on pelvic floor disorders in morbidly
      obese women.
AB  - OBJECTIVE: To evaluate the effect of surgically induced weight loss on pelvic
      floor disorders (PFD) in morbidly obese women. SUMMARY BACKGROUND DATA: Although
      bariatric surgery may lead to the improvement of some obesity-related
      comorbidities, the resolution of global PFD has not been well described. METHODS:
      Women with a body mass index (BMI) of 35 kg/m(2) or more who were considering
      bariatric surgery were asked to complete 2 validated condition-specific
      questionnaires assessing the distress/quality of life impact of PFD, total and by
      domain (pelvic organ prolapse, colorectal-anal, and urogenital). Women who
      achieved a > or =50% excess body weight loss after surgery were asked to complete
      the same questionnaires for comparison. RESULTS: Of the 178 women who underwent
      surgery, 46 completed the postoperative questionnaires. Mean age of this group
      was 45 years (range, 20-67), and mean preoperative BMI was 45 kg/m(2) (range, 35
      75). The prevalence of PFD symptoms improved from 87% before surgery to 65% after
      surgery (P = 0.02, 95% CI: 0.05%-53%). There was a significant reduction in total
      mean distress scores after surgery (P = 0.015, 95% CI: 3.3-32.9), which was
      attributed mainly to the significant decrease in urinary symptoms (P = 0.0002,
      95% CI: 8.2-22.7). Reductions in the scores were noted for the other PFD domains
      as well. Quality of life total scores improved (P = 0.002, 95% CI: 4.8-27.1), as
      did scores in the urinary domain (P = 0.0005, 95% CI: 3.8-13.5) and the pelvic
      organ prolapse domain (P = 0.015, 95% CI: 0.6-9.5). Age, parity, history of
      complicated delivery, percent excess body weight loss, BMI, type of weight loss
      procedure and presence of diabetes mellitus and hypertension had no predictive
      value for postoperative outcomes. CONCLUSION: Surgically induced weight loss has
      a beneficial effect on symptoms of PFD in morbidly obese women.

PMID- 19106679
TI  - Impact of laparoscopic colorectal resection on surgical site infection.
AB  - OBJECTIVES: This study aimed to identify the risk factors of surgical site
      infection (SSI) in elective colorectal resection and the strategy for prevention
      of SSI in modern era of colorectal surgery. BACKGROUND: The practice of
      colorectal surgery has undergone remarkable evolution recently because of
      application of laparoscopic resection. This could affect SSI in colorectal
      patients. An updated investigation of SSI under current practice of colorectal
      surgery would provide valuable information. METHODS: This was a prospective study
      of SSI on 1011 patients, who had elective colorectal resection in a university
      teaching hospital, during January 2002 to December 2006. Standard definition and
      postoperation follow-up of SSI were adopted through collaboration between
      surgeons and wound surveillance program of Infection Control Unit. Risk factors
      of SSI were evaluated. Logistic regression was used to perform multivariate
      analysis and decide independent risk factors of SSI. RESULTS: The overall rate of
      incisional SSI and organ/space SSI was 4.8% and 1.7%, respectively. Rate of
      incisional SSI in open and laparoscopic colorectal resection was 5.7% and 2.7%,
      respectively. Anastomotic leakage was the only factor that predicted organ/space
      SSI (P < 0.01). Independent risk factors of incisional SSI included blood
      transfusion [P = 0.047; odds ratio (OR) = 2.43; 95% confidence interval (CI): 1.0
      5.9], anastomotic leakage (P < 0.01; OR = 6.5; 95% CI: 2.3-18.6), and open
      colorectal resection (P = 0.037; OR = 2.36; 95% CI: 1.1-5.3). CONCLUSION: In
      current practice of colorectal surgery, operative factors are more important than
      patient factors for SSI. Good surgical technique to reduce anastomotic leakage
      and reduce blood transfusion has paramount importance in SSI prevention.
      Laparoscopic surgery was associated with reduction of rate of SSI by more than
      50% when compared with open surgery and would have a strong impact on the
      prevention of surgical infection.

PMID- 19106680
TI  - Laparoscopic resection for rectal cancers: lessons learned from 579 cases.
AB  - OBJECTIVE: The aim of this study is to evaluate the short-term outcomes and long
      term survival of laparoscopic rectal cancer resection at a single institution
      with 579 cases over a 15-year period. SUMMARY BACKGROUND DATA: The use of
      laparoscopic resection for colon cancer has been shown to be safe with comparable
      oncological outcomes. However, the role of laparoscopic resection for rectal
      cancer is still controversial with few studies looking into long-term outcomes.
      METHODS: From May 1992 to April 2007, 579 patients underwent laparoscopic
      resection for rectosigmoid and rectal cancer. The clinical data of these patients
      were retrospectively reviewed from a prospectively collected database. Data
      evaluated includes short- and long-term results, with survival outcomes
      calculated using the Kaplan-Meier method. RESULTS: Over this 15-year period, 316
      patients had laparoscopic anterior resection for rectosigmoid and upper rectal
      cancer, 152 patients had laparoscopic sphincter-saving total mesorectal excision,
      92 patients had laparoscopic abdominoperineal resection, 17 patients had
      laparoscopic Hartmann procedure for rectal cancer, and 2 patients had
      proctocolectomy. The median age of these patients was 68 years (range, 35-95).
      The overall early and late operative morbidity was 18.8% and 9.7%, respectively.
      Conversion to open surgery was required in 5.4%of patients. Anastomotic leak rate
      was 3.5%. The median follow-up time was 56 months (range, 8-288). Port-site
      recurrence occurred in 2 patients. Locoregional recurrence occurred in 7.4% of
      patients after curative resection. The overall 5- and 10-year survivals for
      rectal cancer were 70% and 45.5%, respectively. The cancer-specific 5- and 10-
      year survival was 76% and 56%, respectively. CONCLUSIONS: The results of this
      study with large number of patients over a long follow-up period suggested that
      laparoscopic resection for rectal cancer is safe with good long-term oncological
      outcomes.

PMID- 19106681
TI  - Breast conserving surgery for multifocal breast cancer.
AB  - OBJECTIVE: The purpose of this study is to examine the oncological safety of
      breast conserving surgery (BCS) for patients with multifocal breast cancer.
      SUMMARY BACKGROUND DATA: Few studies have reported about BCS for multifocal
      breast cancer. BCS for multifocal cancer has a risk of local failure in previous
      reports, whereas recent studies reported the feasibility of BCS. However, because
      all studies have dealt with a small number of patients, multifocal breast cancer
      is still considered a relative contraindication for BCS. METHODS: This
      retrospective study includes 478 patients with multifocal breast cancer who
      underwent BCS or mastectomy and 930 with unifocal cancer who underwent BCS for
      stage 0-II. Multifocal cancer was defined as 2 or more distinct cancers in the
      same quadrant. Of 478 patients, 147 underwent BCS and 331 underwent mastectomy.
      We compared the local recurrence rate (LRR), disease free survival, and overall
      survival for BCS with mastectomy for multifocal cancer. In addition, the LRR of
      BCS for multifocal cancer was compared for unifocal cancer. RESULTS: There is no
      significant difference in stage distribution and other clinical and pathologic
      characteristics except Her-2/neu for stage IIA between BCS and mastectomy for
      multifocal cancer. The mean follow-up period was 59.33 months (range, 1.00
      177.20) for breast conserving group and 64.98 months (range, 6.23-196.03) for
      mastectomy group. The 5-year overall survival was 93.38% for BCS and 94.53% for
      mastectomy (log rank P = 0.208). The 5-year disease-free survival was 89.08% for
      BCS and 91.88% for mastectomy (log rank P = 0.451). The local failure occurred in
      3 (2.0%) of 147 patient underwent BCS, 3 (0.9%) of 331 patients underwent
      mastectomy (P = 0.378). Compared with BCS for unifocal cancer patients, the LRR
      of patients with multifocal cancer was not statistically different (2.0% for
      multifocal, 1.3% for unifocal; P = 0.445). CONCLUSIONS: Our study demonstrates
      that BCS for multifocal breast cancer is oncologically safe in selected patients.

PMID- 19106682
TI  - Video-assisted skin-sparing breast-conserving surgery for breast cancer and
      immediate reconstruction with autologous tissue.
AB  - OBJECTIVE: To analyze therapeutic results of video-assisted breast-conserving
      surgery (VA-BCS) for early stage breast cancer. BACKGROUND: VA-BCS for breast
      cancer has been developed in Japan, and is indicated for breast cancer
      unaccompanied by skin involvement. The surgical incision is made at an
      inconspicuous site, followed by skin-sparing partial mastectomy (SSPM) and
      immediate reconstruction of the breast. This technique affords good cosmetic
      results. The long-term results are reported herein. METHODS: VA-BCS was performed
      on 551 patients. The skin incision was made as a peri-areolar incision or at the
      midaxillary line. Skin-sparing partial mastectomy was performed using an
      endoscope and the lifting and tunneling method. Morbidity, curability, and degree
      of satisfaction with regard to cosmesis were analyzed. RESULTS: Skin necrosis in
      22 patients (4.0%) and necrosis of fatty tissue-muscle flap in 17 patients (3.1%)
      were recorded as postoperative complications. No other serious complications were
      encountered. Local recurrence occurred in 23 patients (4.2%) after a mean follow
      up of 38.4 months. Distant-metastasis-free survival rate at 66 months was 100%
      for Tis, 95.5% for T1, and 90.7% for T2. Overall survival rate was 100% for Tis,
      97.3% for T1, and 95.7% for T2. Degree of satisfaction with surgery as
      investigated by questionnaire was "good" for 76.1% of patients. CONCLUSION: VA
      BCS for early stage breast cancer showed no association with increases in local
      or distant organ recurrence. The technique yielded improved cosmesis and a high
      degree of patient satisfaction. Follow-up observation of patients for a longer
      period is necessary, but VA-BCS seems useful for local treatment of breast
      cancer.

PMID- 19106683
TI  - Postoperative pancreatic fistulas: preventing severe complications and reducing
      reoperation and mortality rate.
AB  - BACKGROUND: Postoperative pancreatic fistula (POPF) is responsible for severe
      complications and death in patients who underwent pancreatic surgery. The
      reported success rate of conservative treatment is around 80%. Therefore up to
      20% of patients usually need surgical treatment that can be repeated in some.
      Uncontrolled sepsis and massive hemorrhage are the main causes for mortality in
      this setting. METHOD: Four hundred forty-five patients underwent surgery for
      pancreatic diseases (January 1993-August 2007); 70 of them developed a POPF. An
      early aggressive treatment based on interventional radiology was applied to all
      patients. The drain's track and/or percutaneous approach was used to insert
      catheters into the peripancreatic fluid collection/s or abscess/es. The position
      of catheters was verified at least once a week. Surgery was performed in case of
      failure of conservative approach. RESULTS: Conservative treatment (approach by
      drain's track in 49, percutaneous in 16, mixed in 2) was successful in 67
      patients. A patient under dialysis had the drains inserted during an emergency
      surgery for peritonitis 6 days after surgery; a second patient underwent repeated
      surgical debridement, and a third patient underwent a procedure on the abdominal
      wall to separate a POPF from a colonic fistula. No patient with diagnosed POPF
      died. CONCLUSIONS: Early aggressive interventional radiology allowed managing
      conservatively 95.7% of POPF preventing severe complications and avoiding death.

PMID- 19106684
TI  - The inflammatory pancreatic head mass: significant differences in the anatomic
      pathology of German and American patients with chronic pancreatitis determine
      very different surgical strategies.
AB  - BACKGROUND: The indications for surgery and the surgical strategy selected for
      chronic pancreatitis (CP) vary widely, perhaps because of unaccounted
      characteristics of different patient populations such as the "inflammatory mass"
      in the head of the pancreas, commonly described in Europe but not in America.
      METHODS: We compared the pancreatic morphology, anatomic complications,
      indications leading to intervention, and the operation performed in 93
      consecutive patients with CP operated upon either at a German (n = 48) or an
      American (n = 45) center specializing in pancreatic surgery. Pretreatment
      computed tomography/magnetic resonance imaging scans were reevaluated by 2
      independent radiologists, especially to measure the anterior-posterior diameter
      of the pancreatic head (the inflammatory mass). RESULTS: The prevalence of
      endocrine and exocrine insufficiency was not significantly different. The median
      diameter of the pancreatic head mass was significantly larger in the German group
      (4.5 vs. 2.6 cm, P < 0.001). Inflammatory mass-dependent symptoms [gastric outlet
      obstruction (9/48 vs. 1/45; P = 0.02) and hemorrhage (7/48 vs. 0/45; P = 0.013)]
      were more frequent in the German group. Bile duct stenosis (19/48 vs. 11/43; P =
      0.18) and suspicion of malignancy (5/48 vs. 11/43; P = 0.10) were comparable,
      whereas chronic pain (15/48 vs. 28/43; P = 0.001) was a more frequent indication
      for surgery in the US group. Splenic or portal vein thrombosis was found only in
      the German group. The duration of nonoperative therapy was significantly longer
      in the German group (median 56 vs. 26 months; P = 0.02). In the US group, a
      pancreatoduodenectomy with antrectomy was performed in most (89%) cases, whereas
      in the German group a duodenum-preserving head resection was preferred in more
      than half (25/47) of the cases (P < 0.001). CONCLUSIONS: Symptoms, duration of
      conservative therapy, and selection of surgical treatment all differed
      significantly between German and American patients with CP. These differences
      seem to be dependent upon surprising but unexplained disparities in the
      pathologic pancreatic anatomy between the 2 populations.

PMID- 19106685
TI  - Ischemic complications after pancreaticoduodenectomy: incidence, prevention, and
      management.
AB  - OBJECTIVE: To assess prevalence, prevention, and management strategy of visceral
      ischemic complications after pancreaticoduodenectomy (PD). BACKGROUND: Ischemic
      complications after PD resulting from preexisting celiac axis (CA), superior
      mesenteric artery (SMA), stenosis, or intraoperative arterial trauma appear as an
      underestimated cause of death. Their prevention and adequate management are
      challenging. METHODS: From 1995 to 2006, 545 PD were performed in our
      institution. All patients were evaluated by thin section multidetector computed
      tomography (CT) with arterial reconstruction to detect and class SMA or CA
      stenosis. Hemodynamical significance of stenosis was assessed preoperatively by
      arteriography for atherosclerotic stenosis and intraoperatively by gastroduodenal
      artery clamping test for CA compression by median arcuate ligament. Significant
      atherosclerotic stenosis was stented or bypassed, whereas CA compression was
      treated by median arcuate ligament division during PD. Multidetector-CT accuracy
      to detect arterial stenosis, results of revascularization procedures, and both
      prevalence and prognosis of ischemic complications after PD were analyzed.
      RESULTS: Among 62 (11%) stenoses detected by multidetector-CT, 27 (5%) were
      hemodynamically significant, including 23 CA compressions by median arcuate
      ligament, 2 CA, and 2 SMA atherosclerotic stenoses, respectively. All
      atherosclerotic stenoses were successfully treated by preoperative stenting (n =
      3) or bypass (n = 1). Among the 23 cases who underwent median arcuate ligament
      division, 3 (13%) failed due to 1 CA injury and 2 misdiagnosed intrinsic CA
      stenoses. Overall, 6 patients developed ischemic complications, due to
      intraoperative hepatic artery injury (n = 4), unrecognized SMA atherosclerotic
      stenosis (n = 1), or CA fibromuscular dysplasia (n = 1). Five (83%) of them died,
      representing 36% of the 14 deaths of the whole series (overall mortality = 2.6%).
      Overall, CT detected significant arterial stenosis with a 96% sensitivity and
      determined etiology of CA stenosis with a 92% accuracy. CONCLUSIONS: Ischemic
      complications are an underestimated cause of death after PD and are due to
      preexisting stenoses of CA and SMA, or intraoperative hepatic artery injury.
      Preexisting arterial stenoses are detected by routine multidetector CT.
      Preoperative endovascular stenting for intrinsic stenosis, division of median
      arcuate ligament for extrinsic compression, and meticulous dissection of the
      hepatic artery can contribute to minimize ischemic complications.

PMID- 19106686
TI  - Solitary large hepatocellular carcinoma: a specific subtype of hepatocellular
      carcinoma with good outcome after hepatic resection.
AB  - OBJECTIVE: To evaluate and compare the clinical and pathologic characteristics
      and outcomes after hepatic resection of large hepatocellular carcinoma (SLHCC),
      small HCC (SHCC), and nodular HCC (NHCC). SUMMARY BACKGROUND DATA: Traditional
      viewpoint insists that the classification and prognosis of HCC are determined by
      the size of HCC. As a result, large HCC is often considered as advanced and
      unresectable. However, we have observed a unique type of HCC-SLHCC, which is
      large in size but exhibits good clinical, pathologic, and molecular biologic
      characteristics as well as prognosis. METHODS: From January 1992 to December
      2002, a total of 481 consecutive patients were diagnosed with HCC and received
      hepatic resection. In this series of patients, the clinical and pathologic data,
      surgical outcome, and long-term survival of patients with SLHCC (group A, n =
      260) were analyzed retrospectively and compared with patients who had SHCC (group
      B, n = 135) or NHCC (group C, n = 86). Postresection prognostic factors of HCC
      were also evaluated by univariate and multivariate analysis using Cox's
      proportional hazards model. RESULTS: The clinical and pathologic characteristics
      of SLHCC and SHCC were similar except for tumor necrosis and tumor size. Patients
      of SLHCC had significantly longer operative time, higher intraoperative blood
      loss, higher intraoperative blood transfusion, and higher postoperative morbidity
      than SHCC. However, the 2 groups were similar in duration of hospital stay and
      overall morbidity. Overall survival and disease-free survival in group A and
      group B were similar and significantly better than those in group C. Multivariate
      analysis revealed that large amount of intraoperative blood transfusion and vein
      invasion were independently significant factors for overall survival of patients
      with HCC. CONCLUSION: The clinical and pathologic characteristics and the outcome
      after hepatic resection of SLHCC are similar to that of SHCC, but significantly
      better than NHCC. We propose SLHCC as a specific subtype of HCC and hepatic
      resection as its choice of standard treatment.

PMID- 19106687
TI  - Prospective validation of the "fifty-fifty" criteria as an early and accurate
      predictor of death after liver resection in intensive care unit patients.
AB  - BACKGROUND: Postoperative liver failure after hepatectomy has been identified by
      the association of prothrombin time <50% and serum bilirubin >50 micromol/L (the
      "50-50" criteria). Whether these criteria are of prognostic value in a
      prospective study remains unknown. OBJECTIVE: To determine prospectively the
      prognostic value of the 50-50 criteria on day 3 and day 5 in intensive care unit
      (ICU) patients after hepatectomy. METHODS: From January 2005 to February 2007,
      among 436 elective liver resections, 99 (23%) consecutive patients aged 58 +/- 17
      years were admitted postoperatively in ICU with a mean SAPSII 25 +/- 10.
      Malignant disease was present in 87 and major resections (< or =3 segments) were
      performed in 79 (80%) cases. The underlying liver parenchyma was abnormal in 59
      (59%) cases including cirrhosis, fibrosis, or steatosis >30% in 19, 23, and 17
      patients, respectively. RESULTS: The 50-50 criteria were present on day 3 in 10
      patients and on day 5 in 13. Ten patients (10, 6%) died in ICU. Survivors with
      these criteria were characterized by early aggressive support including
      reoperation and/or liver assist system. Nonsurvivors were more often cirrhotic,
      had significantly higher SAPS II and more frequently postoperative prolonged
      mechanical ventilation. The 50-50 criteria on days 3 and 5 were predictors of
      death on multivariate analysis [OR (95% CI): 12.7 (2.3-71.4), OR (95% CI): 29.4
      (4.9-167), respectively]. CONCLUSIONS: After hepatic resection, results of this
      prospective study validate the 50-50 criteria as a predictive factor of mortality
      in ICU on both days 3 and 5. These criteria allow an early diagnosis of
      postoperative liver failure, which may contribute to reduce mortality in ICU
      patients after hepatectomy.

PMID- 19106689
TI  - Multifocality in retroperitoneal sarcoma: a prognostic factor critical to
      surgical decision-making.
AB  - OBJECTIVE: To evaluate the significance of multifocality on overall survival (OS)
      in patients with retroperitoneal sarcoma (RPS) and establish a data-derived,
      prognostically and therapeutically useful definition of sarcomatosis. SUMMARY
      BACKGROUND DATA: The incidence, clinical features, and prognostic significance of
      multifocality in RPS is unknown. No current standardized definition for
      sarcomatosis is available. METHODS: We conducted a retrospective analysis of 393
      patients with primary or recurrent nonmetastatic RPS treated at a comprehensive
      cancer center between 1996 and 2006. Baseline and treatment variables were
      compared in patients with unifocal and multifocal disease. A multivariate model
      was used to evaluate the association of multifocality and OS and identify
      additional prognostic factors in patients with multifocal disease. RESULTS: The
      median follow-up time for all patients was 69 months; 79 patients (20%) presented
      with multifocal disease. The 5-year OS rate was less in the multifocal group
      compared with the unifocal group (31% vs. 60%, respectively; P < 0.0001). After
      multivariate analysis, multifocality remained an independent predictor of worse
      OS {hazard ratio (HR) 1.7 (95% confidence interval (CI), 1.2-2.5); P = 0.004}.
      Additionally, patients with more tumors had significantly worse prognosis (>7
      tumors, HR 2.1 (95% CI, 1.1-3.9); P = 0.03), with a 5-year OS rate of 7%.
      CONCLUSIONS: Multifocal RPS is associated with worse OS in patients with either
      primary or recurrent RPS; Patients with >7 tumors had the worst prognosis. This
      criterion can be used to define sarcomatosis, thereby identifying patients whose
      survival will ultimately depend on effective systemic therapy.

PMID- 19106688
TI  - High-intensity focused ultrasound ablation for the treatment of colorectal liver
      metastases during an open procedure: study on the pig.
AB  - OBJECTIVE: To demonstrate in a porcine model that high-intensity focused
      ultrasound (HIFU) with toroid-shaped emitters may have a role in treating
      unresectable colorectal liver metastases. SUMMARY BACKGROUND DATA: Surgical
      resection is the only curative option for colorectal hepatic metastases. Only 20%
      of patients are suitable for surgery. Many ablative techniques have been assessed
      but several limitations have been documented: traumatic puncture of the
      parenchyma, limited size of lesions, and inability to monitor the treatment in
      real time. METHODS: A HIFU device with 256 toroid-shaped emitters and integrated
      ultrasound imaging probe was used. Single lesions, induced in 40 seconds, and
      juxtaposition of 6 single lesions were created under ultrasound guidance on 13
      pigs. The lesions were studied on sonograms, macroscopically and microscopically
      up to 30 days after the treatment. RESULTS: Ninety percent of the HIFU lesions
      were immediately hypoechoic on ultrasound imaging. The average coagulated volume
      obtained from a 40 seconds total exposure in the liver was 7.0 +/- 2.5 cm (1.5
      20.0), average diameter: 19.5 +/- 3.8 mm (10.0-29.0). Using the real-time
      visualization of the treated region, single lesions were easily juxtaposed to
      produce larger lesions up to 6 cm in diameter without any major complication.
      CONCLUSIONS: This toroid HIFU device allows short treatment times,
      noninvasiveness regarding the liver and real time ultrasound guidance. It seems
      to be simpler and more reliable to use than current ablative methods.
      Additionally, lesions through large vessels (up to 5 mm) being feasible,
      treatment of some juxta-vascular metastases should be possible.

PMID- 19106690
TI  - Impact of statistical approaches for handling missing data on trauma center
      quality.
AB  - OBJECTIVE: To determine whether imputed data can be used to produce unbiased
      hospital quality measures. BACKGROUND: Different methods for handling missing
      data may influence which hospitals are designated as quality outliers. METHODS:
      Monte-Carlo simulation study based on 63,020 patients with no missing data in 68
      hospitals using the National Trauma Data Bank (NTDB, version 6.1). Patients were
      assigned missing data for the motor component of the Glasgow coma scale (GCS)
      conditional on their observed clinical risk factors. Multiple imputation was then
      used to "fill in" the missing data. Hospital risk-adjusted quality measures
      (observed-to-expected mortality ratio) based either on (1) imputed data, (2)
      excluding patients with missing data (complete case analysis), or (3) excluding
      the predictor with missing data were compared with hospital quality based on the
      true data (no missing data). Pair-wise comparisons of hospital quality were
      performed using the intraclass correlation coefficient (ICC) and the kappa
      statistic. RESULTS: With 10% of the data missing, the level of agreement between
      multiple imputation and the true data (ICC = 0.99 and kappa = 0.87) was better
      compared with the level of agreement between complete case analysis and the true
      data (ICC = 0.93 and kappa = 0.62). Excluding the predictor (motor GCS) with
      missing data from the risk adjustment model resulted in the least amount of
      agreement with quality assessment based on the true data (ICC = 0.88 and kappa =
      0.46). CONCLUSION: Multiple imputation can be used to impute missing data and
      yields hospital quality measures that are nearly identical to those based on the
      true data. Simply excluding patients with missing data or excluding risk factors
      with missing data from hospital quality assessment yields substantially inferior
      quality measures.

PMID- 19106691
TI  - Transplantation of monocyte-derived hepatocyte-like cells (NeoHeps) improves
      survival in a model of acute liver failure.
AB  - OBJECTIVE: Investigation of the efficacy of implantation of monocyte-derived
      hepatocyte-like cells (NeoHeps) in acute liver failure. SUMMARY BACKGROUND DATA:
      Extended liver resection or split liver transplantation is still associated with
      high morbidity and mortality because of postoperative liver insufficiency. In
      view of liver support systems, implantation of isolated hepatocytes or hepatocyte
      like cells such as NeoHeps is increasingly under discussion. METHODS: Twenty-four
      hours before subtotal hepatectomy, cells of different origin [A: human
      mononuclear cells (24 x 10(6)); B: NeoHeps (16 x 10(6)); C: NeoHeps (24 x 10(6));
      D: rat hepatocytes (24 x 10(6))] were injected into the spleen of Wistar rats.
      After an observation period of 5 days, animal survival, postoperative weight, and
      signs of encephalopathy were recorded. At the end of the observation period,
      blood was collected for laboratory analysis. RESULTS: Transplantation of both rat
      hepatocytes and NeoHeps significantly improved animal survival when compared with
      control animals (group A: 21%), reaching 72% in group D (P = 0.001), 50% in group
      C (P = 0.04), and 36% in group B (P = 0.22). Moreover, animals in these groups
      postoperatively experienced less frequently signs of encephalopathy, as well as
      earlier weight increase when compared with group A. DISCUSSION: Hepatocyte
      transplantation is a practicable and successful treatment option in case of liver
      insufficiency because implantation of NeoHeps or primary rat hepatocytes had an
      improving effect on survival. The promising data of the present study warrants
      further analysis to elucidate the role of NeoHeps in treatment of acute
      postoperative liver failure to a greater extent.

PMID- 19106692
TI  - Prevalence and cost of full-time research fellowships during general surgery
      residency: a national survey.
AB  - OBJECTIVE: To quantify the prevalence, outcomes, and cost of surgical resident
      research. SUMMARY BACKGROUND DATA: General surgery is unique among graduate
      medical education programs because a large percentage of residents interrupt
      their clinical training to spend 1 to 3 years performing full-time research. No
      comprehensive data exists on the scope of this practice. METHODS: Survey sent to
      all 239 program directors of general surgery residencies participating in the
      National Resident Matching Program. RESULTS: Response rate was 200 of 239 (84%).
      A total of 381 of 1052 trainees (36%) interrupt residency to pursue full-time
      research. The mean research fellowship length is 1.7 years, with 72% of trainees
      performing basic science research. A significant association was found between
      fellowship length and postresidency activity, with a 14.7% increase in clinical
      fellowship training and a 15.2% decrease in private practice positions for each
      year of full-time research (P < 0.0001). Program directors at 31% of programs
      reported increased clinical duties for research fellows as a result of
      Accreditation Council for Graduate Medical Education work hour regulations for
      clinical residents, whereas a further 10% of programs are currently considering
      such changes. It costs $41.5 million to pay the 634 trainees who perform research
      fellowships each year, the majority of which is paid for by departmental funds
      (40%) and institutional training grants (24%). CONCLUSIONS: Interrupting
      residency to perform a research fellowship is a common and costly practice among
      general surgery residents. Although performing a research fellowship is
      associated with clinical fellowship training after residency, it is unclear to
      what extent this practice leads to the development of surgical investigators
      after postgraduate training.

PMID- 19106693
TI  - Trends in the quality of highly cited surgical research over the past 20 years.
AB  - OBJECTIVE: To evaluate whether the methodologic quality of the most highly cited
      surgical clinical evidence has improved over the past 20 years. SUMMARY
      BACKGROUND DATA: There have been increasing efforts to promote the practice of
      evidence-based medicine among surgeons, although it is unclear whether high
      quality evidence is being used. METHODS: A bibliometric review was performed
      among general surgery and medicine journals to identify the 50 most highly cited
      general surgery clinical research studies from 4 consecutive time periods (1985
      1989, 1990-1994, 1995-1999, 2000-2004). Methodologic characteristics and overall
      data quality for all 200 highly cited studies were assessed by 3 independent
      reviewers using the validated GRADE scoring system and trends over time were
      analyzed. RESULTS: Among 200 extracted articles, the quality of evidence was
      graded as very low in the majority of studies (48%); fewer studies contained data
      of low (13%), moderate (13%), or high (26%) quality. Study quality significantly
      improved over the time periods examined, with an increase in the proportion of
      studies graded as high quality from 12% in 1985 to 1989 to 40% in 2000 to 2004 (P
      < 0.001). The improvement in data quality over time was associated with an
      increased proportion of randomized trials (26% vs. 48%; P < 0.05) and increased
      reporting of adjusted, multivariate regression analyses (22% vs. 54%; P < 0.001).
      CONCLUSIONS: There have been significant improvements in the quality of the most
      highly cited surgical evidence, characterized by more randomized trials and
      improved statistical methodology. These findings suggest that surgeons are
      increasingly recognizing and citing higher quality surgical evidence.

PMID- 19106694
TI  - Professional oversight of physician expert witnesses: an analysis of complaints
      to the Professional Conduct Committee of the American Association of Neurological
      Surgeons, 1992-2006.
AB  - OBJECTIVE: To investigate the role of the professional conduct review program
      that is operated by the American Association of Neurological Surgeons (AANS). The
      program adjudicates complaints against AANS members for their work as expert
      witnesses in medical malpractice litigation. SUMMARY BACKGROUND DATA:
      Policymakers worry that physician expert witnesses who espouse unfounded views in
      malpractice cases may fuel inappropriate litigation. A growing number of
      professional societies have sought to oversee their members' work as expert
      witnesses by instituting standards to regulate this conduct and enforcing those
      standards through formal disciplinary procedures. The AANS runs the longest
      established and busiest program of this kind in the country. Plaintiffs' lawyers
      and consumer advocates have questioned the even-handedness of this form of self
      regulation. METHODS: We reviewed the confidential case summaries of all 59
      complaints involving charges of inappropriate expert witness testimony
      adjudicated by the AANS Professional Conduct Committee from 1992 to 2006. We
      developed descriptive categories for the characteristics of the complainant and
      respondent, the types of misconduct alleged, and the outcomes of the review,
      including penalties imposed. RESULTS: The most common type of allegation was
      presentation of testimony that misrepresented the standard of care. Nineteen
      complaints (32%) were dismissed, but 40 (68%) resulted in sanctions ranging from
      censure to expulsion from membership. Both the frequency of complaints and length
      of sanctions have increased in the last 4 years. Although the AANS is highly
      attentive to procedural fairness, the overwhelming majority (57/59, 97%) of
      complaints related to testimony from witnesses acting for plaintiffs.
      CONCLUSIONS: Professional organizations may play a useful role in oversight of
      expert witness conduct, provided they maintain procedural fairness and strive for
      impartiality, as the AANS program seems to have done. However, from a policy
      perspective, this form of oversight is incomplete and should be complemented by
      other mechanisms aimed at ensuring the quality of physician testimony.

PMID- 19106695
TI  - Postoperative delirium in the elderly: risk factors and outcomes.
AB  - OBJECTIVE: The purpose of this study was to describe the natural history,
      identify risk factors, and determine outcomes for the development of
      postoperative delirium in the elderly. BACKGROUND: Postoperative delirium is a
      common and deleterious complication in geriatric patients. METHODS: Subjects
      older than 50 years scheduled for an operation requiring a postoperative
      intensive care unit admission were recruited. After preoperative informed written
      consent, enrolled subjects had baseline cognitive and functional assessments.
      Postoperatively, subjects were assessed daily for delirium using the confusion
      assessment method-intensive care unit. Patients were also followed for outcomes.
      RESULTS: During the study period, 144 patients were enrolled before major
      abdominal (40%), thoracic (53%), or vascular (7%) operations. The overall
      incidence of delirium was 44% (64/144). The average time to onset of delirium was
      2.1 +/- 0.9 days and the mean duration of delirium was 4.0 +/- 5.1 days. Several
      preoperative variables were associated with an increased risk of delirium
      including older age (P < 0.001), hypoalbuminemia (P < 0.001), impaired functional
      status (P < 0.001), pre-existing dementia (P < 0.001), and pre-existing
      comorbidities (P < 0.001). In a multivariable logistic regression model, pre
      existing dementia remains the strongest risk factor for the development of
      postoperative delirium. Worse outcomes, including increased length of stay (P <
      0.001), postdischarge institutionalization (P < 0.001), and 6 month mortality (P
      = 0.001), occurred in subjects who developed delirium. CONCLUSIONS: In the
      current study, delirium occurred in 44% of elderly patients after a major
      operation. Pre-existing cognitive dysfunction was the strongest predictor of the
      development of postoperative delirium. Outcomes, including an increased rate of 6
      month mortality, were worse in patients who developed postoperative delirium.

PMID- 19106697
TI  - Sublingual immunotherapy: where do we stand? Present and future.

PMID- 19106698
TI  - Interactions between helminth parasites and allergy.
AB  - PURPOSE OF REVIEW: To review the findings of recent human studies of the
      association between helminth parasite infections and allergy and discuss their
      potential relevance to public health. RECENT FINDINGS: Different helminth
      parasites may have different effects on allergy that may depend on the timing or
      intensity of the exposure or host genetic factors. Infections with Trichuris
      trichiura in early life are associated with a reduced prevalence of allergen skin
      test reactivity later in life and infants of helminth-infected mothers have been
      reported to have a reduced prevalence of eczema. Hookworm infection has been
      associated with a reduced prevalence of asthma in Ethiopia. Several studies have
      reported that anti-Ascaris IgE is an important risk factor for asthma, but this
      could be explained by an enhanced ability of atopics to produce IgE. Toxocara
      infections may be associated with an increased risk of wheeze in some populations
      that may be caused by the host response to the parasite or by parasite-enhanced
      Th2 responses to aeroallergens. SUMMARY: Although helminth infections can
      modulate the host inflammatory response directed against the parasite, a causal
      association between helminths and atopic diseases remains uncertain.

PMID- 19106700
TI  - Current world literature.

PMID- 19106699
TI  - The role of innate immunity in the pathogenesis of asthma.
AB  - PURPOSE OF REVIEW: The increase in prevalence of allergic diseases, in particular
      of asthma, poses great difficulties to healthcare institutions in industrialized
      countries. According to the hygiene hypothesis, a linkage exists between exposure
      towards microbes in early childhood and the development of allergies; however,
      the original view that stimulation of the host's immune system by microbes
      exclusively protects against the development of allergies and asthma has been
      challenged by recent studies, which are summarized in this review. RECENT
      FINDINGS: Recent studies in mice revealed that infection with a series of
      microbes in the context of allergen exposure enhances antigen sensitization.
      Furthermore, in studies using purified toll-like receptor ligands and live
      bacteria, innate immune activation via MyD88 has been shown to be a causative
      factor in sensitization. The view that innate immune activation, under
      circumstances yet to be elucidated, may be a causative factor for the development
      of allergies is backed by epidemiologic data showing a protective effect of
      genetic variants, which impair toll-like receptor signaling. CONCLUSION: Recent
      studies in mice suggest that innate immune stimulation via microbes or their
      compounds, in a dose and time-dependent manner, can cause allergen sensitization,
      and this notion has lately been supported by epidemiologic data.

PMID- 19106703
TI  - Current world literature.

PMID- 19106705
TI  - Trans fatty acids and cardiovascular risk markers: does the source matter?

PMID- 19106702
TI  - Recent developments in HIV and the kidney.
AB  - PURPOSE OF REVIEW: Antiretroviral therapy has been immensely successful in
      reducing the incidence of opportunistic infections and death after HIV infection.
      This has resulted in heightened interest in noninfectious comorbidities including
      kidney disease. This review focuses on recent progress in our understanding of
      the clinical epidemiology of HIV-associated kidney disease. RECENT FINDINGS:
      Acute renal failure in the highly active antiretroviral therapy era is associated
      with delayed HIV diagnosis. The incidence of acute renal failure rapidly declines
      in patients who receive HIV care, which includes the provision of highly active
      antiretroviral therapy to patients with advanced HIV infection. The prevalence of
      chronic kidney disease among HIV-infected patients is approximately 17%, and
      chronic kidney disease is associated with older age, advanced HIV infection,
      metabolic and vascular disease, and use of indinavir and tenofovir. Black
      patients are at increased risk of progression to end-stage renal disease,
      particularly if not receiving highly active antiretroviral therapy. Although
      survival of patients requiring dialysis remains poor, renal transplantation is an
      increasingly promising treatment modality for HIV-associated end-stage renal
      disease. SUMMARY: The various forms of HIV-associated kidney dysfunction are now
      much better defined. The burden of chronic kidney disease is likely to escalate
      as a result of increasing life expectancy and ageing of HIV-infected patients.

PMID- 19106706
TI  - The effect of antidiabetic drugs on genes regulating lipid metabolism.
AB  - PURPOSE OF REVIEW: Hyperglycaemia and dyslipidaemia are closely linked, yet,
      there has been difficulty in demonstrating that lowering blood sugar reduces
      cardiovascular events. The pathways linking abnormalities in fatty acid
      metabolism, insulin resistance and diabetes with abnormalities in cholesterol
      metabolism are being rapidly unravelled with new understandings of the effect of
      antidiabetic drugs on lipoprotein metabolism. The purpose of this review is to
      explore the recent literature. RECENT FINDINGS: Postprandial lipoproteins are now
      firmly established as a postprandial risk factor. Both insulin resistance and
      diabetes are associated with abnormalities in chylomicron production, and
      clearance and regulatory genes have been identified. Metformin, the most commonly
      used drug in type 2 diabetes, has multiple actions affecting numerous genes. The
      peroxisome proliferator-activated receptor-gamma regulation of insulin
      sensitivity and the important effects on lipoproteins are described. The entero
      insulin axis and glucagon-like peptide-1 agonists, together with inhibitors of
      dipeptidyl peptidase 4 may have lipoprotein implications, but the evidence at
      present is sparse even though glucagon-like peptide-1 is found in high
      concentrations in the lymph. SUMMARY: Although antidiabetic drugs affect lipid
      metabolism, there is little evidence to suggest that these drugs can prevent
      atherosclerosis in diabetes and some may promote atherosclerosis through their
      adverse effect on lipoproteins.

PMID- 19106707
TI  - The initiatives and outcomes for cardiovascular risks that can be achieved
      through paediatric counselling.
AB  - PURPOSE OF REVIEW: Atherosclerosis is a result of a lifelong process. Obesity is
      associated with increased serum levels of inflammatory markers in children and
      adolescents like in adults, promoting coronary heart disease risk in an
      increasing proportion of young adults. Dietary patterns have a central role in
      the development of coronary heart disease through effects on serum lipids and
      development of body fatness. It is the purpose of this review to describe
      progress in this field. RECENT FINDINGS: The supervised counselling aiming at low
      saturated fat intake by children decreases serum total and low-density
      lipoprotein (LDL) cholesterol values significantly and keeps them at lower level
      through childhood. It is not associated with abnormal growth or defects in
      cognitive or pubertal development. Coronary heart disease risk factor levels
      measured in childhood markedly influence vascular function and structure.
      SUMMARY: To diminish the risk of premature atherosclerosis, the prime target in
      counselling of young children and their parents should be a change in fat quality
      rather than fat quantity. However, to prevent obesity, excessive consumption of
      total fat and sucrose needs to be avoided. Early commencement of statin therapy
      in children and adolescents suffering from familial hypercholesterolemia is
      beneficial in prevention of vascular atherosclerosis.

PMID- 19106708
TI  - Endothelial glycocalyx as potential diagnostic and therapeutic target in
      cardiovascular disease.
AB  - PURPOSE OF REVIEW: The endothelial glycocalyx has emerged as a potential
      orchestrator of vascular homeostasis. Under physiological conditions, the
      glycocalyx is an important contributor to the regulation of vascular permeability
      for macromolecules as well for the adhesion of circulating cells. In line, the
      potential role of the glycocalyx in maintaining the antiatherogenic properties of
      the vessel wall may have important clinical implications. In the present review,
      we provide an overview of recent developments and a glance at the future of
      establishing endothelial glycocalyx as a crucial player in cardiovascular
      protection. RECENT FINDINGS: Novel methods to estimate glycocalyx dimensions in
      vivo (using Orthogonal Polarization Spectral imaging or Sideview Darkfield
      imaging) as well as progressive insight into the enzymes involved in glycocalyx
      synthesis will be crucial in the assessment of this structure as a potential
      surrogate marker or therapeutic target for cardiovascular risk. The validation of
      these 'imaging' techniques and the integration with glycocalyx degradation
      products in plasma will allow us to test the value of the endothelial glycocalyx
      in estimating cardiovascular risk. SUMMARY: The endothelial glycocalyx,
      protecting the vascular wall against atherogenic influents, could be used for
      cardiovascular risk stratification. For this purpose, new methods to estimate
      glycocalyx dimension are promising.

PMID- 19106709
TI  - Bibliography. Current world literature. Nutrition and metabolism.

PMID- 19106710
TI  - Genetics and molecular biology: identifying adipocytes and their origin.

PMID- 19106711
TI  - Lipid metabolism: reviews of HDL and cholesterol efflux, ethanol and hepatic
      lipid metabolism and lipid disorders during childhood.

PMID- 19106712
TI  - Hyperlipidaemia and cardiovascular disease: nonlipid-lowering effects of omega-3
      fatty acids, statins and fibrates.

PMID- 19106713
TI  - Atherosclerosis: cell biology and lipoproteins.

PMID- 19106714
TI  - Therapy and clinical trials: management of diabetic dyslipidemia.

PMID- 19106715
TI  - Should acute myocardial infarction be considered in the differential diagnosis of
      headache?
AB  - AIM: Headache as the only presenting symptom of acute myocardial infarction (MI)
      is an extremely uncommon phenomenon. The aim of this report is to describe a 61
      year-old female patient with exertional headaches being the solely presentation
      of acute MI. METHODS: As there were no complaints of chest pains or any other
      symptoms suggestive for MI, she underwent extensive neurological work-up. The
      correct diagnosis, however, was established only after a detailed description of
      the localization and radiation of her pains was obtained. CONCLUSION: The
      importance of a thoroughly obtained anamnesis for the early recognition of cases
      with MI presenting with headaches, as well as the difference of opinion
      concerning the correct diagnosis which may occur between the internist and the
      cardiologist, are discussed.

PMID- 19106716
TI  - Score predicting imminent delivery in pregnant women calling the emergency
      medical service.
AB  - OBJECTIVE: To develop a telephone score predicting imminent delivery. METHODS:
      Prospective multicenter (n=38) study including pregnancies of 33 weeks or more
      amenorrhea (n=3.499). Values in points were assigned to risk factors (Cox's
      model) and the score tested on a validation cohort and receiver operating
      characteristic curves. RESULTS: Risk was increased if the caller was panicking or
      declared delivery to be imminent (+3 points), if the pregnant woman could not be
      spoken to herself (+3), was aged 26-35 (+3) years, was having frequent
      contractions (from +4 to +8), had the urge to push (+2 to +6 depending on
      starting time), had a history of rapid or home delivery (+2), or had not been
      followed up during pregnancy (+8). Nulliparous women (-7) or those on tocolytic
      treatment (-3) were less at risk. The score is reproducible and relevant.
      CONCLUSION: Score predicting imminent delivery scoring during calls is a valid
      means of assessing risk of delivery.

PMID- 19106717
TI  - Comparison of the Full Outline of Unresponsiveness Score Coma Scale and the
      Glasgow Coma Scale in an emergency setting population.
AB  - BACKGROUND: The Glasgow Coma Scale (GCS) is the most widely used tool for the
      evaluation of the level of consciousness. The Full Outline of Unresponsiveness
      (FOUR) Score is a new coma Scale that was developed considering the limitations
      of the GCS, and has been found to be useful in an intensive care setting. We
      aimed to compare FOUR Score and GCS in the emergency setting. METHODS: All
      patients older than 17 years who presented with an altered level of
      consciousness, after any trauma to the head or with neurological complaints were
      included in this study. Three-month mortality, in-hospital mortality, and poor
      outcome using a Modified Rankin Scale (MRS) of 3-6 points were used as the
      primary outcome measures. RESULTS: A total of 185 patients were included in the
      study. Area under the curve (AUC) values in predicting 3-month mortality for GCS
      was 0.726 [P=0.0001 and 95% confidence interval (CI): 0.656-0.789] and 0.776
      (P=0.0001 and 95% CI: 0.709-834) for FOUR Score. AUC in predicting hospital
      mortality for GCS was 0.735 (P=0.0001 and 95% CI: 0.655-0.797) and 0.788
      (P=0.0001 and 95% CI: 0.722-0.844) for FOUR Score. AUC in predicting poor outcome
      (Modified Rankin Scale: 3-6) was 0.720 (P=0.001 and 95% CI: 0.650-784) for GCS
      and 0.751 (P=0.0001 and 95% CI: 0.682-0.812) for FOUR Score. CONCLUSION: The new
      coma Scale, FOUR Score, is not superior to the GCS. However, the combination of
      the eye and motor components of FOUR Score is a valuable tool that can be used
      instead of either the FOUR Score or GCS.

PMID- 19106718
TI  - Handling of drug-related emergencies: an evaluation of emergency medical
      dispatch.
AB  - AIMS: Documenting the quality of emergency dispatch centres handling of emergency
      calls regarding intoxicated unconscious patients. METHODS: Interview with eight
      emergency dispatch centre directors and a nationwide survey among 313 dispatchers
      in Norway were performed. In addition, a customized scoring system was used to
      evaluate dispatcher log recordings of real cases. The recordings were compared
      with information from corresponding ambulance records. RESULTS: Ninety-nine
      percent of the dispatchers stated that they used the Norwegian protocol for
      medical emergencies and 89% of them found it useful. The interviews, the survey,
      and the recordings, however, documented frequent deviation from the protocol.
      This instructs ambulance dispatch for any unconscious patient, but 21% stated
      that they would not dispatch any resource for an unconscious patient without
      further survey in alcohol-related cases. This was significantly more often
      (P<0.05) than for the narcotic, combination and prescription - drug-related cases
      with 4, 10 and 7%, respectively. The recordings revealed deviation from the
      protocol with dispatchers only determining the patients' level of consciousness
      and respiratory status in 64 and 70% of the cases, respectively. For 16% of the
      cases, the dispatcher did not ask the caller about consciousness at all, even
      though these patients later were found with reduced consciousness. CONCLUSION: On
      the basis of the interviews and the survey, cases were handled according to
      guidelines. The log recordings, however, disclosed deviation from the protocol.
      Alcohol intoxication was associated with higher rate of deviation from the
      protocol compared with other intoxications.

PMID- 19106719
TI  - Thyrotoxic hypokalemic periodic paralysis: a life-threatening syndrome.
AB  - Hypokalemic periodic paralysis is a rare life-threatening syndrome, potentially
      reversible when detected at an early stage. Hypokalemia may also occur in other
      conditions characterized by muscle weakness. Acute myopathy associated with
      thyrotoxicosis has been described in Asian populations, although it seldom
      affects Caucasians or African-Americans. It can be difficult to recognize in
      western populations. Acute recurrent episodes of flaccid paralysis, symmetrically
      affecting the proximal muscles of the lower limbs, either following strenuous
      physical activity or carbohydrate overindulgence, is the usual presentation.
      Hypokalemia seems to result from transcellular shifts of potassium rather than
      losses. A case of thyrotoxic hypokalemic periodic paralysis occurring in a young
      Caucasian male diagnosed with Graves' disease is reported.

PMID- 19106720
TI  - Metabolic acidosis in a patient with type 1 diabetes mellitus complicated by
      methanol and amitriptyline intoxication.
AB  - Diabetic ketoacidosis (DKA) is a widely known acute metabolic complication of
      diabetes mellitus (DM), which can be potentially fatal. It is not difficult to
      diagnose when a patient with DM comes with symptoms such as coma, fruity breath,
      hyperglycemia, acidosis, and tachypnea. If the patient has not been diagnosed
      with DM before, then other sicknesses characterized by an increased anion gap
      should be considered. A 12-year-old boy with type 1 DM and repeated earlier
      admissions for DKA was admitted to the emergency department in another apparent
      case of DKA with coma, hyperglycemia, and profound metabolic acidosis. When his
      condition did not improve with initial treatment, intoxication was suspected as
      an alternate cause of his condition. Further laboratory tests detected methanol
      and amitriptyline. The patient underwent hemodialysis and recovered completely.
      This case illustrates that a seemingly obvious medical condition can mask serious
      intoxication. This report is the only publication on two different entities
      characterized by an increased anion gap and at the end the patient has been cured
      completely without any complications.

PMID- 19106721
TI  - Back pain in adult: what's your diagnosis? Suction bullae and burning injury.

PMID- 19106722
TI  - A national survey of the implementation of the new specialist certificate of
      emergency medicine in France.

PMID- 19106723
TI  - Football and Rugby (... and other sport events?) emergency department
      attendances.

PMID- 19106724
TI  - Public reporting in health care: how do consumers use quality-of-care
      information? A systematic review.
AB  - BACKGROUND: One of the underlying goals of public reporting is to encourage the
      consumer to select health care providers or health plans that offer comparatively
      better quality-of-care. OBJECTIVE: To review the weight consumers give to quality
      of-care information in the process of choice, to summarize the effect of
      presentation formats, and to examine the impact of quality information on
      consumers' choice behavior. The evidence is organized in a theoretical consumer
      choice model. DATA SOURCES: English language literature was searched in PubMed,
      the Cochrane Clinical Trial, and the EPOC Databases (January 1990-January 2008).
      STUDY SELECTION: Study selection was limited to randomized controlled trails,
      controlled before-after trials or interrupted time series. Included interventions
      focused on choice behavior of consumers in health care settings. Outcome measures
      referred to one of the steps in a consumer choice model. The quality of the study
      design was rated, and studies with low quality ratings were excluded. RESULTS:
      All 14 included studies examine quality information, usually CAHPS, with respect
      to its impact on the consumer's choice of health plans. Easy-to-read presentation
      formats and explanatory messages improve knowledge about and attitude towards the
      use of quality information; however, the weight given to quality information
      depends on other features, including free provider choice and costs. In real
      world settings, having seen quality information is a strong determinant for
      choosing higher quality-rated health plans. CONCLUSIONS: This review contributes
      to an understanding of consumer choice behavior in health care settings. The
      small number of included studies limits the strength of our conclusions.

PMID- 19106725
TI  - Differences in services provided by hospices based on home health agency
      certification status.
AB  - BACKGROUND: Similar patient populations and favorable regulations have led many
      home health agencies to become Medicare and/or Medicaid certified as hospice
      agencies (mixed), but home health and hospice programs differ in focus and scope.
      Little research has been performed examining the differences between mixed
      hospices and those agencies only certified as hospices (nonmixed). OBJECTIVES: To
      describe the differences in agency characteristics between mixed and nonmixed
      agencies; and to compare frequencies of service provision by mixed and nonmixed
      agencies. RESEARCH DESIGN: Cross-sectional study using data from the 2000
      National Home and Hospice Care Survey. SUBJECTS: A total of 760 Medicare and/or
      Medicaid certified hospice agencies providing services during the survey,
      including 393 mixed agencies (52% of sample) and 367 nonmixed hospices. MEASURES:
      Survey responses by administrators about services provided by agency. RESULTS:
      Nonmixed agencies were significantly more likely than mixed agencies to provide
      many types of services, including: volunteers [96.1% vs. 77.4%, respectively;
      odds ratio (OR): 7.27; 95% confidence interval (CI): 5.26-10.05], social services
      (96.1% vs. 93.5%; OR: 1.70; 95% CI: 1.20-2.40), spiritual care (95.1% vs. 77.8%;
      OR: 5.53; 95% CI: 4.13-7.41), bereavement care (93.5% vs. 79.8%; OR: 3.63; 95%
      CI: 2.80-4.72), counseling (89.5% vs. 70.2%; OR: 3.62; 95% CI: 2.92-4.48), and
      physician services (87.2% vs. 52.0%; OR: 6.30; 95% CI: 5.18-7.66). In logistic
      regression models, these differences remained significant after adjustment for
      census region, operation by a hospital, number of patients and number of hospice
      patients, and Medicare and Medicaid hospice certification status. CONCLUSIONS:
      Mixed agencies provide a narrower range of services to hospice patients than
      nonmixed agencies, including fewer services considered cornerstones of hospice
      treatment.

PMID- 19106726
TI  - Community characteristics affecting emergency department use by Medicaid
      enrollees.
AB  - OBJECTIVES: In seeking to identify modifiable, system-level factors affecting
      emergency department (ED) use, we used a statewide Medicaid database to study
      community variation in ED use and ascertain community characteristics associated
      with higher use. METHODS: This historical cohort study used administrative data
      from July 1, 2003 to December 31, 2004. Residence ZIP codes were used to assign
      all 555,219 Medicaid enrollees to 130 primary care service areas (PCSAs). PCSA
      characteristics studied included rural/urban status, presence of hospital(s),
      driving time to hospital, and several measures of primary care capacity.
      Statistical analyses used a 2-stage model. In the first stage (enrollee level),
      ED utilization rates adjusted for enrollee demographics and medical conditions
      were calculated for each PCSA. In the second stage (community level), a mixed
      effects linear model was used to determine the association between PCSA
      characteristics and ED use. RESULTS: ED utilization rates varied more than 20
      fold among the PCSAs. Compared with PCSAs with primary care capacity less than
      need, PCSAs with capacity 1 to 2 times the need had 0.12 (95% CI: -0.044, -0.20)
      fewer ED visits/person/yr. Compared with PCSAs with the nearest hospital
      accessible within 10 minutes, PCSAs with the nearest hospital >30 minutes' drive
      had 0.26 (95% CI: -0.38, -0.13) fewer ED visits/person/yr. CONCLUSIONS: Within
      this Medicaid population, ED utilization was determined not only by patient
      characteristics but by community characteristics. Better understanding of system
      level factors affecting ED use can enable communities to improve their health
      care delivery systems-augmenting access to care and reducing reliance on EDs.

PMID- 19106727
TI  - Patient safety climate in 92 US hospitals: differences by work area and
      discipline.
AB  - BACKGROUND: Concern about patient safety has promoted efforts to improve safety
      climate. A better understanding of how patient safety climate differs among
      distinct work areas and disciplines in hospitals would facilitate the design and
      implementation of interventions. OBJECTIVES: To understand workers' perceptions
      of safety climate and ways in which climate varies among hospitals and by work
      area and discipline. RESEARCH DESIGN: We administered the Patient Safety Climate
      in Healthcare Organizations survey in 2004-2005 to personnel in a stratified
      random sample of 92 US hospitals. SUBJECTS: We sampled 100% of senior managers
      and physicians and 10% of all other workers. We received 18,361 completed surveys
      (52% response). MEASURES: The survey measured safety climate perceptions and
      worker and job characteristics of hospital personnel. We calculated and compared
      the percent of responses inconsistent with a climate of safety among hospitals,
      work areas, and disciplines. RESULTS: Overall, 17% of responses were inconsistent
      with a safety climate. Patient safety climate differed by hospital and among and
      within work areas and disciplines. Emergency department personnel perceived worse
      safety climate and personnel in nonclinical areas perceived better safety climate
      than workers in other areas. Nurses were more negative than physicians regarding
      their work unit's support and recognition of safety efforts, and physicians
      showed marginally more fear of shame than nurses. For other dimensions of safety
      climate, physician-nurse differences depended on their work area. CONCLUSIONS:
      Differences among and within hospitals suggest that strategies for improving
      safety climate and patient safety should be tailored for work areas and
      disciplines.

PMID- 19106728
TI  - Two pharmacy interventions to improve refill persistence for chronic disease
      medications: a randomized, controlled trial.
AB  - BACKGROUND: Despite the proven effectiveness of many medications for chronic
      diseases, many patients do not refill their prescriptions in the required
      timeframe. OBJECTIVE: Compare the effectiveness of 3 pharmacist strategies to
      decrease time to refill of prescriptions for common chronic diseases. RESEARCH
      DESIGN/SUBJECTS: A randomized, controlled clinical trial with patients as the
      unit of randomization. Nine pharmacies within a medium-sized grocery store chain
      in South Carolina were included, representing urban, suburban, and rural areas
      and patients from a variety of socioeconomic backgrounds. Patients (n = 3048)
      overdue for refills for selected medications were randomized into 1 of 3
      treatment arms: (1) pharmacist contact with the patient via telephone, (2)
      pharmacist contact with the patient's prescribing physician via facsimile, and
      (3) usual care. MEASURES: The primary outcome was the number of days from their
      recommended refill date until the patient filled a prescription for any
      medication relevant to his/her chronic disease. Prescription refill data were
      obtained routinely from the pharmacy district office's centralized database.
      Patient disposition codes were obtained by pharmacy employees. An intent-to-treat
      approach was used for all analyses. RESULTS: There were no significant
      differences by treatment arm in the study outcomes. CONCLUSIONS: Neither of the
      interventions is more effective than usual care at improving persistence of
      prescription refills for chronic diseases in overdue patients.

PMID- 19106729
TI  - Health coaching via an internet portal for primary care patients with chronic
      conditions: a randomized controlled trial.
AB  - BACKGROUND: Efforts to enhance patient-physician communication may improve
      management of underdiagnosed chronic conditions. Patient internet portals offer
      an efficient venue for coaching patients to discuss chronic conditions with their
      primary care physicians (PCP). OBJECTIVES: We sought to test the effectiveness of
      an internet portal-based coaching intervention to promote patient-PCP discussion
      about chronic conditions. RESEARCH DESIGN: We conducted a randomized trial of a
      nurse coach intervention conducted entirely through a patient internet-portal.
      SUBJECTS: Two hundred forty-one patients who were registered portal users with
      scheduled PCP appointments were screened through the portal for 3 target
      conditions, depression, chronic pain, mobility difficulty, and randomized to
      intervention and control groups. MEASURES: One-week and 3-month patient surveys
      assessed visit experiences, target conditions, and quality of life; chart
      abstractions assessed diagnosis and management during PCP visit. RESULTS: Similar
      high percentages of intervention (85%) and control (80%) participants reported
      discussing their screened condition during their PCP visit. More intervention
      than control patients reported their PCP gave them specific advice about their
      health (94% vs. 84%; P = 0.03) and referred them to a specialist (51% vs. 28%; P
      = 0.002). Intervention participants reported somewhat higher satisfaction than
      controls (P = 0.07). Results showed no differences in detection or management of
      screened conditions, symptom ratings, and quality of life between groups.
      CONCLUSIONS: Internet portal-based coaching produced some possible benefits in
      care for chronic conditions but without significantly changing patient outcomes.
      Limited sample sizes may have contributed to insignificant findings. Further
      research should explore ways internet portals may improve patient outcomes in
      primary care. ClinicalTrials.gov registration NCT00130416.

PMID- 19106730
TI  - Rates of complete colonic evaluation after incomplete colonoscopy and their
      associated factors: a population-based study.
AB  - BACKGROUND: With the increasing use of colonoscopy there is growing concern about
      the quality of these procedures. OBJECTIVE: To evaluate the rates of complete
      colonic evaluation after an incomplete colonoscopy and their associated factors.
      METHODS: Men and women > or =50 years old living in Ontario on January 1, 1997
      who did not have a prior history of colorectal cancer, inflammatory bowel
      disease, or colonic resection comprised the inception cohort. Receipt of an
      incomplete colonoscopy between January 1, 1997 and December 31, 2002 was
      determined. Individuals were followed over 1 year and the time from incomplete
      colonoscopy to complete colonic evaluation was estimated using Kaplan-Meier
      analysis. A generalized estimating equations model was used to evaluate the
      association between patient, physician, and setting factors and complete colonic
      evaluation. RESULTS: Twenty thousand one hundred sixty-six individuals had an
      incomplete colonoscopy, of whom 29.4% underwent complete colonic evaluation
      within 1 year after the procedure. Women > or =80 years were less likely to
      undergo complete colonic evaluation (odds ratio: 0.89; 95% confidence interval:
      0.79-0.99), as were those who had their colonoscopy in a private office or clinic
      (odds ratio: 0.77; 95% confidence interval: 0.67-0.89). CONCLUSIONS: Only 29.4%
      of individuals with an incomplete colonoscopy underwent complete colonic
      evaluation within 1 year after the procedure. Women > or =80 years and those who
      had their colonoscopy in a private office or clinic were less likely to undergo
      complete colonic evaluation. The quality of care provided to older women and
      colonoscopy practice in office settings may be suboptimal.

PMID- 19106731
TI  - Relative efficiency of the EQ-5D, HUI2, and HUI3 index scores in measuring health
      burden of chronic medical conditions in a population health survey in the United
      States.
AB  - OBJECTIVE: We sought to compare the ability of the EQ-5D, Health Utilities Index
      Mark 2 (HUI2), and HUI Mark 3 (HUI3) index scores to discriminate between
      respondents based on the presence or absence of chronic medical conditions in a
      population health survey. METHODS: Secondary analyses were conducted with data
      from a probability sample (n = 3480, mean age: 42.5 years, male: 42.4%, Hispanic:
      28.6%) of the 2001 noninstitutionalized US general adult population. F-statistic
      ratios were used to evaluate the relative efficiency of the EQ-5D, HUI2, and HUI3
      in differentiating respondents with or without each of 18 chronic medical
      conditions, and differentiating respondents with low- or high-burden conditions.
      RESULTS: In comparing respondents with and without chronic medical conditions,
      the F-statistic values of these 3 indices were not significantly different,
      except for EQ-5D versus HUI2 [mean F-statistic ratio: 0.79, 95% confidence
      interval (CI): 0.59-0.98]. In comparing respondents with a low-burden condition
      with those with a high-burden condition, the F-statistic values of EQ-5D and HUI2
      index scores were similar, while those for EQ-5D versus HUI3 (mean: 0.79; 95% CI:
      0.66-0.92) and for HUI2 versus HUI3 (mean: 0.83; 95% CI: 0.71-0.95) were
      significantly less than 1.0. The overall ceiling effects of the EQ-5D, HUI2, and
      HUI3 index scores were 48.9%, 15.4%, and 15.3%, respectively. CONCLUSIONS:
      Although the EQ-5D seems to be marginally less informative, the EQ-5D, HUI2, and
      HUI3 index scores were generally comparable in determining health burden of
      chronic medical conditions in this population health survey data.

PMID- 19106732
TI  - Using the EQ-5D index score as a predictor of outcomes in patients with type 2
      diabetes.
AB  - OBJECTIVE: To examine whether index scores based on the EQ-5D, a 5-item generic
      health status measure, are an independent predictor of vascular events, other
      major complications and mortality in people with type 2 diabetes and to quantify
      the relationship between these scores and future survival. SUBJECTS: Five-year
      cohort study involving 7348 patients with type 2 diabetes, aged between 50-75
      years who had been recruited to the FIELD (Fenofibrate Intervention and Event
      Lowering in Diabetes) study from Australia and New Zealand. MEASURES:
      Multivariate Cox proportional hazard regression models were used to estimate the
      hazard ratio associated with index scores derived from the EQ-5D on: (1)
      cardiovascular events (including coronary heart disease event, stroke,
      hospitalization for angina, or cardiovascular death); (2) other major diabetes
      related complications (heart failure, amputation, renal dialysis, and lower
      extremity ulcer); and (3) death from any cause. Life table methods were used to
      derive expected survival for patients with different index scores. RESULTS: After
      adjusting for standard risk factors, a 0.1 higher index score (derived from the
      UK algorithm) was associated with an additional 7% (95% CI: 4-11%) lower risk of
      vascular events, a 13% (95% CI: 9-17%) lower risk of complications, and up to 14%
      (95% CI: 8-19%) lower rate of all-cause mortality. CONCLUSIONS: Index scores
      derived from the EQ-5D are an independent predictor of the risk of mortality,
      future vascular events, and other complications in people with type 2 diabetes.
      This should be taken into account when extrapolating health outcomes such as
      quality-adjusted life years (QALYs).

PMID- 19106733
TI  - Identification and validation of vertebral compression fractures using
      administrative claims data.
AB  - INTRODUCTION: Vertebral compression fractures (VCFs) are the most common type of
      osteoporotic fracture. Administrative claims data might be useful to identify
      VCFs, but this approach to case finding has received limited evaluation. METHODS:
      Using the administrative claims databases of a large regional US health care
      organization, we identified adults with a claim with a VCF diagnosis code from
      January 2003 to June 2004 and excluded persons with malignancy. We examined the
      positive predictive values (PPV) of several claims algorithms to correctly
      identify any confirmed (prevalent or incident) VCF, and separately, incident
      VCFs. RESULTS: A total of 259 persons were identified with a VCF suspected based
      on their administrative claims data. A claims algorithm that required a VCF
      diagnosis on any claim had a PPV to identify any confirmed VCF of 87% (95%
      confidence interval (CI), 82-91%). The PPV of this algorithm to identify a
      confirmed incident VCF was 46% (95% CI, 37-54%). An algorithm that required a
      spine imaging test followed by a physician visit with a VCF code within 10 days,
      or a hospitalization with a primary diagnosis code, had higher PPVs (PPV = 93%;
      95% CI, 87-98% for any confirmed VCF; PPV = 61%; 95% CI, 49-74% for incident
      VCFs). CONCLUSIONS: A simple case finding approach to identify VCFs using
      administrative claims data can identify prevalent VCFs with high accuracy but
      misclassified more than half of incident VCFs. A more complex claims algorithm
      may be used but still will result in some misclassification of incident VCFs.

PMID- 19106734
TI  - Impact of acquired comorbidities on all-cause mortality rates among older breast
      cancer survivors.
AB  - BACKGROUND: Breast cancer survivors with higher numbers of comorbidities at the
      time of primary treatment suffer higher rates of all-cause mortality than
      comparatively healthier survivors. The effect of time-varying comorbidity status
      on mortality in breast cancer survivors, however, has not been well investigated.
      OBJECTIVE: We examined longitudinal comorbidity in a cohort of women treated for
      primary breast cancer to determine whether accounting for comorbidities acquired
      after baseline assessment influenced the hazard ratio of all-cause mortality
      compared with an analysis using only baseline comorbidity. METHODS: Cox
      proportional hazards adjusted for age, race/ethnicity, and exercise habits were
      modeled using (1) only a baseline Charlson index; (2) 4 Charlson index values
      collected longitudinally and entered as time-varying covariates, with missing
      values addressed by carrying forward the prior observation; and (3) the 4
      longitudinal Charlson scores entered as time-varying covariates, with missing
      values multiply imputed. RESULTS: The 3 modeling strategies yielded similar
      results; Model 1 HR: 1.4 per unit increase in Charlson index, 95% confidence
      interval (CI): 1.2-1.7; Model 2 HR: 1.3, 95% CI: 1.1-1.5; and Model 3 HR: 1.4,
      95% CI: 1.2-1.6. CONCLUSIONS: Our findings indicate that a unit increase in the
      Charlson comorbidity index raises the hazard rate for all-cause mortality by
      approximately 1.4-fold in older women treated for primary breast cancer. The
      conclusion is essentially the same whether accounting only for baseline
      comorbidity or accounting for acquired comorbidity over a median follow-up period
      of 85 months.

PMID- 19106735
TI  - The utility of prediction models to oversample the long-term uninsured.
AB  - OBJECTIVES: To evaluate the performance of prediction models in identifying the
      long-term uninsured and their utility for oversampling purposes in national
      health care surveys. DATA AND METHODS: Nationally representative data from the
      Medical Expenditure Panel Survey (MEPS) were used to examine national estimates
      of nonelderly adults without health insurance coverage for 2 consecutive years
      and to identify the factors that distinguished them from the short-term uninsured
      and those who are continually insured. The MEPS data were also used in the
      development of the prediction models to identify individuals most likely to
      experience long-term spells without coverage in the future. The prediction models
      were developed using data from the MEPS panel covering 2004-2005 and evaluated
      with an independent MEPS panel. RESULTS: Study findings revealed these prediction
      models to be markedly effective statistical tools in facilitating an efficient
      over-sample of individuals likely to be uninsured for long periods of duration in
      the future. Use of these models for oversampling purposes, to support a 50%
      increase in sample yield over a self-weighting design, permits the selection of
      the target sample of individuals who are continuously uninsured for 2 consecutive
      years in the most cost-efficient manner. This methodology allows for an overall
      sample size specification for nonelderly adults that is at least 25% lower than a
      design without access to the predictor variables from a screening interview or
      without application of oversampling techniques. CONCLUSIONS: This examination of
      the performance of probabilistic models, to both identify and facilitate an
      oversample of the long-term uninsured, demonstrates the viability of these model
      based sampling methodologies for adoption in national health care surveys.

PMID- 19106736
TI  - Funding of tribal health programs linked to lower rates of hospitalization for
      conditions sensitive to ambulatory care.
AB  - OBJECTIVE: To determine first whether higher funding of Tribally Operated Health
      Programs (TOHP) is associated with reduced hospitalizations for ambulatory care
      sensitive conditions (HASC) of the American Indian/Alaska Natives (AIAN) who use
      them after adjusting for characteristics of TOHP service areas; and then whether
      improved ambulatory care with higher levels of funding mediates the association.
      RESEARCH DESIGN: Records in the Indian Health Service (IHS) for California of an
      annual average 42,153 AIAN users of TOHP from 1998 to 2002 were linked with state
      hospital discharge records. We analyzed 3181 HASC for AIAN users of 20 TOHP in
      multilevel Poisson regression models to determine the association of HASC rates
      adjusted for individual age and gender with the Federal Disparity Index for IHS
      funding of TOHP. RESULTS: Higher IHS funding of TOHP was associated with lower
      HASC rates for the AIAN who use them. For TOHP with less than 60% of health care
      costs funded, the HASC rate dropped 12% for every increase of 10% in funding.
      Even adjusting for characteristics of the service areas, the effect was only
      slightly reduced to a value of 9% to 11%. None of the available indicators of
      ambulatory care tested were found to mediate the effects. CONCLUSIONS: Our
      findings are consistent with a policy of IHS funding of all TOHP at a level of at
      least 60% of the health care costs of the AIAN who use the programs, instead of
      the current policy of 40%. Additional research is needed to understand what
      ambulatory care characteristics are improved by the funding.

PMID- 19106737
TI  - The economic value of professional nursing.
AB  - BACKGROUND: Improved understanding of the economic value of registered nurse
      services can help inform staffing decisions and policies. OBJECTIVES: To quantify
      the economic value of professional nursing. METHODS: We synthesize findings from
      the literature on the relationship between registered nurse staffing levels and
      nursing-sensitive patient outcomes in acute care hospitals. Using hospital
      discharge data to estimate incidence and cost of these patient outcomes together
      with productivity measures, we estimate the economic implications of changes in
      registered nurse staffing levels. SUBJECTS: Medical and surgical patients in
      nonfederal acute care hospitals. Data come from a literature review, and hospital
      discharge data from the 2005 Nationwide Inpatient Sample. MEASURES: Patient
      nosocomial complications, healthcare expenditures, and national productivity.
      RESULTS: As nurse staffing levels increase, patient risk of nosocomial
      complications and hospital length of stay decrease, resulting in medical cost
      savings, improved national productivity, and lives saved. CONCLUSIONS: Only a
      portion of the services that professional nurses provide can be quantified in
      pecuniary terms, but the partial estimates of economic value presented illustrate
      the economic value to society of improved quality of care achieved through higher
      staffing levels.

PMID- 19106738
TI  - Mothers of children diagnosed with attention-deficit/hyperactivity disorder:
      health conditions and medical care utilization in periods before and after birth
      of the child.
AB  - BACKGROUND: Analyzing health conditions and medical utilization of mothers of
      children with attention-deficit/hyperactivity disorder (ADHD) can shed light on
      biologic, environmental, and psychosocial factors relating to ADHD. OBJECTIVE: To
      examine health conditions, health care utilization, and costs of mothers of
      children with ADHD in periods before the child was diagnosed. METHODS: Using
      automated data from Northern California Kaiser Permanente we identified mothers
      of children with ADHD, mothers of children without ADHD, and mothers of children
      with asthma. Mothers' diagnostic clusters, health care utilization, and costs
      were compared. Mothers of children with ADHD were compared with mothers of
      children without ADHD and, separately, to mothers of children with asthma.
      RESULTS: Compared with mothers of children without ADHD, mothers of children with
      ADHD were more likely to be diagnosed with numerous medical and mental health
      problems in the 2 years after birth of their child, including depression [odds
      ratio (OR): 1.88], anxiety neuroses (OR: 1.64), obesity (OR: 1.70), and
      musculoskeletal symptoms (OR: 1.51). Results were similar for the year before
      delivery. Mothers of children with ADHD also had higher total health care costs
      per person in the year before ($1,003) and the 2 years after ($953) the birth of
      their child. Mothers of children with ADHD also were diagnosed with more health
      conditions and had higher health care costs than mothers of children with asthma.
      CONCLUSIONS: Our findings suggest that the likelihood of being diagnosed with
      ADHD is related to maternal conditions and use of health services that precede
      the child's diagnosis. Future studies are needed to clarify whether this is due
      to biologic, psychosocial, or environmental factors, or a combination.

PMID- 19106739
TI  - Long-term results of a smoking reduction program.
AB  - INTRODUCTION: There have been few comprehensive evaluations of smoking reduction,
      especially in health care delivery systems, and little is known about its cost,
      maintenance of reduced smoking, or robustness across patient subgroups. METHODS:
      A generally representative sample of 320 adult smokers from an HMO scheduled for
      outpatient surgery or a diagnostic procedure was randomized to enhanced usual
      care or a theory-based smoking reduction intervention that combined telephone
      counseling and tailored newsletters. Outcomes included cigarettes smoked, carbon
      monoxide levels, and costs. RESULTS: Both intervention and control conditions
      continued to improve from 3- to 12-month assessments. Between-condition
      differences using intent-to-treat analyses on both self-report and carbon
      monoxide measures were nonsignificant by the 12-month follow-up (25% vs. 19%
      achieved 50% or greater reductions in cigarettes smoked). The intervention was
      implemented consistently despite logistical constraints and was generally robust
      across patient characteristics (eg, education, ethnicity, health literacy,
      dependence). CONCLUSIONS: In the absence of nicotine replacement therapy, the
      long-term effects of this smoking reduction intervention seem modest and
      nonsignificant. Future research is indicated to enhance intervention effects and
      conduct more comprehensive economic analyses of program variations.

PMID- 19106740
TI  - Comparison of two VA laboratory data repositories indicates that missing data
      vary despite originating from the same source.
AB  - BACKGROUND: Assessing accuracy and completeness of data is an important component
      of conducting research. VA Healthcare System benefits from a highly developed
      electronic medical information system. The Immunology Case Registry was designed
      to monitor costs and quality of HIV care. The Decision Support System was
      developed to monitor utilization and costs of veterans in care. Because these
      systems extract data from the same source using independent methods, they provide
      an opportunity to compare the accuracy and completeness of each. OBJECTIVE: To
      compare overlapping laboratory data from the Veterans Affairs Health Information
      System between 2 data repositories. RESEARCH DESIGN: For hemoglobin, CD4
      lymphocyte counts (CD4), HIV RNA viral load, aspartate aminotransferase, alanine
      aminotransferase, glycosylated hemoglobin, creatinine, and white blood count, we
      calculated the percent of individuals with a value from each source. For results
      in both repositories, we calculated Pearson's correlation coefficients. SUBJECTS:
      A total of 22,647 HIV+ veterans in the Virtual Cohort with a visit in fiscal year
      2002. RESULTS: For 6 out of 9 tests, 68% to 72% of the observations overlapped.
      For CD4, viral load, and glycosylated hemoglobin less than 31% of observations
      overlapped. Overlapping results were nearly perfectly correlated except for CD4.
      CONCLUSIONS: Six of the laboratory tests demonstrated remarkably similar amounts
      of overlap, though Immunology Case Registry and Decision Support System both have
      missing data. Findings indicate that validation of laboratory data should be
      conducted before its use in quality and efficiency projects. When 2 databases are
      not available for comparison, other methods of validation should be implemented.

PMID- 19106742
TI  - Use of mechanical and noninvasive ventilation in black and white chronic
      obstructive pulmonary disease patients within the Veterans Administration health
      care system.
AB  - BACKGROUND: Black patients are more likely than white patients to prefer and
      receive more life-sustaining interventions in advanced stages of disease.
      However, little is known about potential racial differences in use of mechanical
      ventilation (MV), and the newer modality of noninvasive ventilation (NIV), in
      treatment of chronic obstructive pulmonary disease (COPD). OBJECTIVE: To
      determine if rates of MV and NIV use differ among black and white patients
      admitted to Veterans Administration (VA) hospitals for COPD exacerbation.
      RESEARCH DESIGN: Retrospective cohort analysis of VA database FY2003 to FY2005
      including 153 hospitals nationwide. SUBJECTS: All black (n = 479) and white (n =
      31,537) patients admitted with COPD exacerbation. MEASURES: Ventilation use
      during hospitalization as identified by ICD-9-CM codes for MV and NIV.
      Hierarchical logistic regression compared rates of MV or NIV use among black and
      white patients, adjusting for patient characteristics and accounting for hospital
      level variation. RESULTS: Unadjusted rates of MV were higher in black patients
      than in white patients (4.1% vs. 3.0%; P < 0.001), but similar for NIV (6.0% vs.
      6.1%; P = 0.65). The adjusted odds of MV for black patients relative to white
      patients remained higher (OR = 1.27, 95% CI: 1.01-1.54; P < 0.01) while the
      adjusted odds of NIV remained similar (OR = 0.94, 95% CI: 0.82-1.08; P = 0.38).
      CONCLUSIONS: Black patients with COPD exacerbation in VA hospitals are more
      likely than white patients to receive MV, and this difference is not explained by
      available clinical or demographic variables. By contrast, black and white
      patients are equally likely to receive NIV. These findings suggest that
      unmeasured factors, such as patient preferences or disease severity, may be
      affecting the use of MV in this setting and therefore warrant further
      investigation.

PMID- 19106741
TI  - Mortality ascertainment of women veterans: a comparison of sources of vital
      status information, 1979-2002.
AB  - BACKGROUND: To support health research on the unique cohort of women with a
      history of military service, this study assessed the completeness of mortality
      ascertainment for Texas women veterans in Department of Veterans Affairs (VA) and
      non-VA databases. METHODS: We examined female veteran-specific mortality
      ascertainment comparing the VA Beneficiary Identification and Records Locator
      Subsystem Death File (BIRLS DF), VA Patient Treatment Files (PTF), and Social
      Security Administration-Death Master File (SSA-DMF) with Texas death certificate
      data. Databases were deterministically cross-linked, using female sex and social
      security numbers. Deterministic and probabilistic linkage methods were also
      compared. RESULTS: Of 6,297 decedents identified by death certificates, SSA-DMF,
      BIRLS DF, and PTF databases identified 97.5% collectively and 94%, 77%, and 5%
      individually. Compared with Texas death certificates, sensitivity of VA and SSA
      databases improved with increasing age. CONCLUSIONS: This study highlights that
      although the VA and SSA administrative databases have less complete ascertainment
      for younger decedents, combined these electronic databases provide nearly
      complete ascertainment for women veterans. Challenges related to large female
      specific cross-linkage studies are explored, and a need to examine methods for
      female-specific health research studies in the general population is identified.

PMID- 19106743
TI  - Pancreaticopleural fistula.
AB  - OBJECTIVES: Pancreaticopleural fistula (PPF) is an unusual complication of
      chronic pancreatitis. Its diagnosis is obscured by predominance of pulmonary
      symptoms. A review of clinical presentation, etiology, diagnostic, and treatment
      modalities is presented in context of 2 cases from our institution. METHODS: Case
      reports and case series of PPFs in the English literature from 1960 to 2007 were
      identified in the PubMed, OVID, and EMBASE search engines. RESULTS: Fifty-two
      cases of PPF were identified. Common presenting complaint was dyspnea (65%)
      followed by abdominal pain (29%), cough (27%) and chest pain (23%). Computed
      tomography scanning diagnosed PPF in 8 (47%) of 17 patients, endoscopic
      retrograde cholangiopancreatography diagnosed PPF in 25 (78%) of 32 patients, and
      magnetic resonance cholangiopancreatography diagnosed PPF in 8 (80%) of 10
      patients. Twenty-one patients (65%) improved with conservative management alone.
      Interventional therapy (5 endoscopic and 6 surgical interventions) was eventually
      needed in 35% of the patients after failing conservative management. CONCLUSIONS:
      Pancreaticopleural fistula is a rare finding and requires a high index of
      suspicion for patients presenting with chest symptoms or pleural effusion and
      with history of pancreatitis or alcoholism. Magnetic resonance
      cholangiopancreatography is the better initial choice for being a noninvasive
      procedure and for better demonstration of complete main pancreatic duct
      obstruction. Restoring anatomic continuity is important if conservative approach
      fails.

PMID- 19106744
TI  - Homeobox gene CDX2 inhibits human pancreatic cancer cell proliferation by down
      regulating cyclin D1 transcriptional activity.
AB  - OBJECTIVES: Homeobox gene caudal related homeobox gene 2 (CDX2) is an intestine
      specific tumor suppressor gene. This study is intended to investigate the effect
      of CDX2 expression on cell proliferation and cyclin D1 expression in pancreatic
      cancer cells. METHODS: Four pancreatic ductal adenocarcinoma cell lines (PancQGO
      1, BxPC-3, MIAPaCa-2, CFPAC-1), 1 islet carcinoma cell line (QGP-1), and 1
      adenosquamous carcinoma cell line (KP-3) were analyzed for CDX1 and CDX2
      expression using real-time reverse transcription-polymerase chain reaction and
      Western blot analysis. Proliferation of pancreatic cancer cells was analyzed
      using WST-1 assay after CDX2 transfection. Luciferase assay was performed to
      examine the effects of CDX2 on cyclin D1 transcriptional activity. RESULTS: CDX2
      was expressed at a significantly higher level in QGP-1 cells than in KP-3 cells.
      Moreover, CDX2 was expressed at a middle level in 4 pancreatic ductal
      adenocarcinoma cells. Cell proliferation and cyclin D1 mRNA level were inhibited
      significantly after CDX2 transfection in pancreatic cancer cells. Furthermore,
      CDX2 inhibited exogenous nuclear factor kappaB-p65-induced luciferase gene
      expression in a dose-dependent manner. In addition, CDX2 inhibited
      pGL2HIVD1kappaB2-luciferase activity. CONCLUSIONS: CDX2 might play a role in
      inhibiting cell proliferation and repressing cyclin D1 transcriptional activity
      through the proximal nuclear factor kappaB binding site in pancreatic cancer
      cells.

PMID- 19106745
TI  - Inhibition of pancreatic cancer cell proliferation by propranolol occurs through
      apoptosis induction: the study of beta-adrenoceptor antagonist's anticancer
      effect in pancreatic cancer cell.
AB  - OBJECTIVES: Propranolol inhibited pancreatic cancer cell proliferation by
      blocking signaling through the beta-adrenoceptor. We hypothesized that
      propranolol may suppress pancreatic cancer cell growth through induction of
      apoptosis. METHODS: The beta-adrenoceptor antagonist propranolol, beta1
      adrenoceptor antagonist metoprolol, and beta2-adrenoceptor antagonist butoxamine
      were used to induce apoptosis in PC-2 cells. The mRNA and protein expression of
      beta1- and beta2-adrenoceptors was analyzed using reverse transcriptase
      polymerase chain reaction and Western blot. The apoptotic index was determined
      using Hoechst 33342 fluorescent staining, TUNEL, and annexin V and fluorescein
      isothiocyanate/propidium iodide flow cytometry assay. The expression of caspase
      3, caspase 9, and caspase 8 was analyzed using Western blotting. RESULTS: PC-2
      cell line expressed mRNA and protein for both of beta1- and beta2-adrenoceptors.
      The Hoechst staining, TUNEL, and flow cytometry assay documented that the 3 drugs
      increased the number of apoptotic cells; the rate of apoptosis was the highest
      using butoxamine followed by propranolol, whereas the least was using metoprolol.
      beta-Adrenoceptor antagonists therapy affected caspase 3 and caspase 9
      expression. CONCLUSIONS: The rate of apoptosis in PC-2 cells was higher after
      treatment with butoxamine than propranolol, suggesting that propranolol induces
      apoptosis in PC-2 cells via the beta2-adrenoceptors principally. Our data could
      be useful for developing beta-adrenoceptor antagonists for inducing apoptosis in
      pancreatic cancer cells.

PMID- 19106747
TI  - Correlation between obesity and hyperglycemia in acute pancreatitis with systemic
      complications: the third variable problem.

PMID- 19106748
TI  - Microbiology of bile in cholelithiasis patients with and without acute
      pancreatitis.

PMID- 19106749
TI  - Neuroendocrine differentiation of anaplastic carcinoma of the pancreas in a case
      report diagnosed by endoscopic ultrasound-guided fine-needle aspiration cytology.

PMID- 19106750
TI  - Robotic-assisted laparoscopic distal pancreatectomy of a redo case combined with
      autologous islet transplantation for chronic pancreatitis.

PMID- 19106751
TI  - Prevention of recurrent pancreatitis in incomplete pancreas divisum by stenting
      the communicating branch.

PMID- 19106752
TI  - Phenotypic variability in a family with pancreatitis and cystic fibrosis sharing
      common mild CFTR mutation: report on CFTR mutations and their phenotypic
      variability.

PMID- 19106753
TI  - Transcatheter embolization of a pancreatic pseudoaneurysm using a new liquid
      embolic agent, ethylene vinyl alcohol copolymer (onyx).

PMID- 19106754
TI  - Fluconazole prophylaxis in the neonatal intensive care unit.

PMID- 19106755
TI  - Voriconazole and posaconazole resistant Candida pelliculosa fungemia after
      cardiac surgery.

PMID- 19106756
TI  - Neonatal sepsis: a major global public health challenge.

PMID- 19106757
TI  - Pathogens associated with sepsis in newborns and young infants in developing
      countries.
AB  - INTRODUCTION: Knowledge of pathogens causing infections in young infants (up to
      90 days of life) is essential for devising community-based management strategies.
      Most etiological data from developing countries are hospital-based and may have
      little relevance to communities in which most babies are born at home. METHODS:
      We searched the literature for studies from developing countries reporting
      etiology of community-acquired infections (sepsis, pneumonia, meningitis)
      published since 1980. Hospital-based studies reporting early onset sepsis, sepsis
      among babies admitted from, or born at home were included. RESULTS: Of 63
      studies, 13 focused on community-acquired infections, but limited data were
      available from home-born neonates. In the first week of life (3209 isolates),
      Klebsiella species (25%), Escherichia coli (15%), and Staphylococcus aureus (18%)
      were major pathogens. Group B streptococci (GBS) were relatively uncommon (7%),
      although regional differences existed. After the first week of life (835
      isolates), S. aureus (14%), GBS (12%), Streptococcus pneumoniae (12%), and
      nontyphoidal Salmonella species (13%) were most frequent. S. pneumoniae (27%) was
      most common in the postneonatal period (among 141 isolates). Gram-negatives
      predominated (77%) among home-delivered babies (among 170 isolates). CONCLUSIONS:
      Limited information is available on etiology of serious bacterial infections in
      community settings. Hospital-based studies suggest that most infections in the
      first week of life are due to Gram-negative pathogens, and many may be
      environmentally rather than maternally-acquired, owing to unhygienic delivery
      practices. Such practices may also explain the predominance of Gram-negative
      infections among home-born infants, although data from home settings are limited.
      These findings have implications for developing prevention and management
      strategies in communities and hospitals.

PMID- 19106758
TI  - Antimicrobial resistance among neonatal pathogens in developing countries.
AB  - INTRODUCTION: Knowledge of antimicrobial resistance and trends in resistance
      patterns among major pathogens causing infections in young infants (up to 90 days
      of life) is an important component of developing community-based management
      strategies. Hospital-based data suggest alarming rates of resistance to
      ampicillin and gentamicin, the first-line antimicrobial agents recommended by WHO
      for treatment of serious infections in young infants. METHODS: We searched the
      literature published since 1990 for studies from developing countries reporting
      resistance among serious community-acquired infections (including sepsis,
      pneumonia, and meningitis) in young infants. RESULTS: Only 10 relevant reports
      were retrieved. Among the 3 major pathogens studied (Escherichia coli,
      Staphyloccoccus aureus, and Klebsiella species), a high proportion of E. coli
      were ampicillin (72%) and cotrimoxazole (78%) resistant; 19% were resistant to
      third generation cephalosporins. Among Klebsiella species, almost all were
      resistant to ampicillin, 45% to cotrimoxazole, and 66% to third generation
      cephalosporins. Resistance to gentamicin was low among E. coli (13%), but much
      higher among Klebsiella species (60%). Methicillin resistance S. aureus (MRSA)
      was rare (1 of 33 isolates) but 46% were resistant to cotrimoxazole. CONCLUSIONS:
      Antimicrobial resistance data for infections in young infants from community
      based studies were extremely limited. Significant resistance, in particular to
      cotrimoxazole among all pathogens, and to gentamicin and third generation
      cephalosporins among Klebsiella and emerging resistance in E. coli is cause for
      concern. Limited data pose a challenge in devising simple community-based
      management strategies. Further studies from different developing country regions
      are needed to determine prevalence of resistant strains, as well as assess
      regional and time trends.

PMID- 19106759
TI  - Management of newborn infections in primary care settings: a review of the
      evidence and implications for policy?
AB  - BACKGROUND: Long-term, sustainable programs to address high incidence and death
      rates from neonatal infections are required for improving child survival. There
      is an urgent need to define the role of community-based management for neonates
      with serious bacterial infections--both at home and at first-level facilities.
      METHODS: We reviewed available evidence for community-based antibiotic management
      strategies for serious neonatal infections. RESULTS: Nine distinct studies
      contributing data for community-based management of neonatal pneumonia and sepsis
      were identified. In a pooled analysis of 5 controlled trials of community-based
      management of neonatal pneumonia (4 using cotrimoxazole, 1 ampicillin, or
      penicillin), all-cause neonatal mortality showed 27% [95% confidence interval
      (CI): 18%-35%] reduction and pneumonia-specific mortality, 42% (95% CI: 22%-57%).
      Substantial reductions in neonatal mortality have been demonstrated in a
      nonrandomized controlled study in rural India (62% reduction, P < 0.001) and in a
      cluster randomized trial in rural Bangladesh (34% reduction, 95% CI: 7%-53%).
      Reduced case fatalities (0%-3%) with community-based management of neonatal
      sepsis were observed in 2 small uncontrolled studies from India and Guatemala and
      a recent randomized trial from Pakistan. CONCLUSIONS: Although methodological
      limitations preclude estimating the precise contribution of antibiotics toward
      neonatal mortality reduction in community settings in low income countries,
      available data suggest substantial benefit of case management approaches using
      antibiotics for neonatal sepsis in such settings.

PMID- 19106760
TI  - Burden of neonatal infections in developing countries: a review of evidence from
      community-based studies.
AB  - INTRODUCTION: Infections are a major contributor to newborn deaths in developing
      countries. Majority of these deaths occur at home without coming to medical
      attention. The Millennium Development Goal for child survival cannot be achieved
      without substantial reductions in infection-specific neonatal mortality. We
      describe the burden of neonatal infections in developing countries and discuss
      the need for community-based management approaches to improve survival from
      neonatal infections in these countries. METHODS: We reviewed community-based
      studies published since 1990 from developing countries to estimate the rates of
      neonatal and young infant infections and infection-specific neonatal mortality.
      RESULTS: Thirty-two studies reviewed suggest that infections may be responsible
      for 8% to 80% of all neonatal deaths and as many as 42% of deaths in the first
      week of life. Eleven reports provided data on incidence of infections in neonates
      and infants up to 60 days of life. Rates of neonatal sepsis were as high as
      170/1000 live births (clinically diagnosed) and 5.5/1000 live births (blood
      culture-confirmed). CONCLUSIONS: Considerable heterogeneity exists among included
      studies, and more accurate data and standardized methodologies are required.
      However, data indicate that a significant proportion of neonatal deaths in
      developing countries are due to infections. Current recommendations of
      hospitalization and parenteral therapy for managing neonatal infections are
      inadequately followed in developing countries. Approaches for detecting and
      managing serious infections within the community, at home or first-level health
      facilities, may be more effective options in settings where delays and reluctance
      to seek care, health system inefficiencies, socioeconomic and cultural, as well
      as logistic constraints exist.

PMID- 19106761
TI  - Oral antibiotics in the management of serious neonatal bacterial infections in
      developing country communities.
AB  - BACKGROUND: Parenteral antibiotic therapy is the standard of care for treatment
      of serious neonatal infections. This may not be possible, however, in some
      developing country settings with limited health systems capacity. METHODS: We
      reviewed the evidence for treatment of neonatal infections in developing
      countries with oral antibiotics, evaluated properties of oral agents that could
      be considered, and identified priority research questions. RESULTS: Case
      management of pneumonia in developing country community settings suggests that
      this strategy has resulted in substantial reductions in neonatal mortality.
      However, limited available data indicate that injectable antibiotic therapy is
      superior to oral regimens. CONCLUSIONS: Parenteral therapy should be used for
      treatment of serious neonatal infections whenever possible. In settings in which
      this is not possible, however, oral antibiotic therapy is superior to no
      antibiotic therapy. Further research is needed to define subgroups of patients
      and settings in which therapy with oral agents is ethical and effective.

PMID- 19106762
TI  - Parenteral antibiotics for the treatment of serious neonatal bacterial infections
      in developing country settings.
AB  - BACKGROUND: A number of special issues must be considered when selecting simple,
      safe, inexpensive, and effective antimicrobial regimens for treatment of neonatal
      sepsis in developing country community settings. METHODS: We reviewed available
      data regarding pharmacologic profiles of parenteral antibiotics with specific
      attention to properties relevant to their use in the treatment of neonatal
      infections in developing country communities. RESULTS: For community-based
      management of neonatal infections, particularly attractive properties include
      efficacy and safety of extended-interval, intramuscular dosing regimens. The
      penicillins and cephalosporins have relatively favorable efficacy and safety
      profiles. Although the aminoglycosides have narrow therapeutic indices, when used
      appropriately, they are safe and effective. Although inexpensive and effective,
      the potential for significant life-threatening toxicity among neonates associated
      with chloramphenicol makes it the least preferred of the parenteral agents for
      empiric therapy. CONCLUSIONS: The preferred parenteral regimens for community and
      first-level facility use are a combination of procaine penicillin G and
      gentamicin, or ceftriaxone given alone, which are safe and retain efficacy when
      dosed at extended intervals (> or =24 hours) by intramuscular administration.

PMID- 19106763
TI  - Research priorities to reduce global mortality from newborn infections by 2015.
AB  - BACKGROUND: Newborn infections are responsible for approximately one-third of the
      estimated 4.0 million neonatal deaths that occur globally every year.
      Appropriately targeted research is required to guide investment in effective
      interventions, especially in low resource settings. Setting global priorities for
      research to address neonatal infections is essential and urgent. METHODS: The
      Department of Child and Adolescent Health and Development of the World Health
      Organization (WHO/CAH) applied the Child Health and Nutrition Research Initiative
      (CHNRI) priority-setting methodology to identify and stimulate research most
      likely to reduce global newborn infection-related mortality by 2015. Technical
      experts were invited by WHO/CAH to systematically list and then use standard
      methods to score research questions according to their likelihood to (i) be
      answered in an ethical way, (ii) lead to (or improve) effective interventions,
      (iii) be deliverable, affordable, and sustainable, (iv) maximize death burden
      reduction, and (v) have an equitable effect in the population. The scores were
      then weighted according to the values provided by a wide group of stakeholders
      from the global research priority-setting network. FINDINGS: On a 100-point
      scale, the final priority scores for 69 research questions ranged from 39 to 83.
      Most of the 15 research questions that received the highest scores were in the
      domain of health systems and policy research to address barriers affecting
      existing cost-effective interventions. The priority questions focused on
      promotion of home care practices to prevent newborn infections and approaches to
      increase coverage and quality of management of newborn infections in health
      facilities as well as in the community. While community-based intervention
      research is receiving some current investment, rigorous evaluation and cost
      analysis is almost entirely lacking for research on facility-based interventions
      and quality improvement. INTERPRETATION: Given the lack of progress in improving
      newborn survival despite the existence of effective interventions, it is not
      surprising that of the top ranked research priorities in this article the
      majority are in the domain of health systems and policy research. We urge funding
      agencies and investigators to invest in these research priorities to accelerate
      reduction of neonatal deaths, particularly those due to infections.

PMID- 19106764
TI  - The 5-HT3 receptor antagonist, ondansetron, blocks the development and expression
      of ethanol-induced locomotor sensitization in mice.
AB  - Manipulation of the serotonergic system has been shown to alter ethanol
      sensitization. Ondansetron is a 5-HT3 receptor antagonist, reported to attenuate
      cocaine and methamphetamine-induced behavioral sensitization, but no reports are
      available on its role in ethanol-induced behavioral sensitization. Therefore, an
      attempt has been made to assess this issue by using an earlier used animal model
      of ethanol-induced locomotor sensitization. Results indicated that ondansetron
      (0.25-1.0 mg/kg, subcutaneously) given before the challenge dose of ethanol (2.4
      g/kg, intraperitoneally) injection, significantly and dose dependently attenuated
      the expression of sensitization. In addition, ondansetron (1.0 mg/kg,
      subcutaneously) given before ethanol injection on days 1, 4, 7, and 10
      significantly blocked the development (days 1, 4, 7, and 10), and expression (day
      15) of sensitization to the locomotor stimulant effect of ethanol injection.
      Ondansetron had no effect per se on locomotor activity and did not affect blood
      ethanol levels. Therefore, the results raise the possibility that ondansetron
      blocked the development and expression of ethanol-induced locomotor sensitization
      by acting on 5-HT3 receptors.

PMID- 19106766
TI  - Social communication competence and functional adaptation in a general population
      of children: preliminary evidence for sex-by-verbal IQ differential risk.
AB  - OBJECTIVE: The proportion of schoolchildren with mild social communicative
      deficits far exceeds the number diagnosed with an autistic spectrum disorder
      (ASD). We aimed to ascertain both the population distribution of such deficits
      and their association with functional adaptation and cognitive ability in middle
      childhood. METHOD: The parent-report Social and Communication Disorders Checklist
      was administered to participants (n = 8,094) in the Avon Longitudinal Study of
      Parents and Children. We correlated impairment severity with independent clinical
      diagnoses of ASD, cognitive abilities, and teacher-rated maladaptive behavior.
      RESULTS: Social and Communication Disorders Checklist scores were continuously
      distributed in the general population; boys had mean scores 30% higher than
      girls. Social communicative deficits were associated with functional impairment
      at school, especially in domains of hyperactivity and conduct disorders. A sex-by
      verbal IQ interaction effect occurred: verbal IQ was protective against social
      communication impairments across the range of abilities in female subjects only.
      In male subjects, this protective effect did not exist for those with above
      average verbal IQ. CONCLUSIONS: Social communicative deficits are of prognostic
      significance, in terms of behavioral adjustment at school, for boys and girls.
      Their high general population prevalence emphasizes the importance of measuring
      such traits among clinically referred children who do not meet diagnostic ASD
      criteria. Above-average verbal IQ seems to confer protection against social
      communication impairments in female subjects but not in male subjects.

PMID- 19106767
TI  - Guanfacine extended release in children and adolescents with attention
      deficit/hyperactivity disorder: a placebo-controlled trial.
AB  - OBJECTIVE: This study compared the efficacy of guanfacine extended release (GXR),
      a selective alpha(2A)-adrenoceptor agonist, with placebo in children and
      adolescents with attention-deficit/hyperactivity disorder (ADHD). METHOD: This
      double-blind, 9-week, dose-ranging, parallel-design, multicenter trial randomized
      6- to 17-year-olds with ADHD to once-daily oral GXR in 1-, 2-, 3-, and 4-mg doses
      or placebo. Primary outcome was change in total ADHD Rating Scale-IV score from
      baseline to endpoint. Secondary outcomes included changes in scores of
      hyperactive/impulsive and inattentive subscales; clinician and parent ratings;
      duration of clinical effect; and safety measures. RESULTS: Statistically
      significant reductions in ADHD Rating Scale-IV scores were observed from baseline
      to endpoint at all doses of GXR, with effect sizes ranging from 0.43 to 0.62. In
      subjects receiving GXR, mean heart rate and systolic and diastolic blood pressure
      decreased as the dose of GXR increased and then returned toward baseline during
      the dose-maintenance and dose-tapering phases of the trial. Most frequent
      treatment-emergent adverse events (> or = 5%) were somnolence, headache, fatigue,
      sedation, dizziness, irritability, upper abdominal pain, and nausea. Somnolence,
      sedation, and fatigue adverse events emerged within the first 2 weeks of dosing
      and generally resolved by study end. CONCLUSIONS: : Guanfacine extended-release
      was effective in reducing symptoms of ADHD. Adverse events were mild to moderate,
      did not interfere with improvements in attention, and rarely led to
      discontinuation.

PMID- 19106768
TI  - Effectiveness of head-mounted vibrotactile stimulation in subjects with bilateral
      vestibular loss: a phase 1 clinical trial.
AB  - OBJECTIVE: Evaluate the effectiveness of a head-mounted vibrotactile prosthesis
      for balance improvement in subjects with severe bilateral vestibular loss (BVL).
      STUDY DESIGN: Crossover study. SETTING: Academic tertiary care vestibular
      function test center. PATIENTS: Five subjects with severe BVL as defined by video
      oculography, rotational chair, and computerized dynamic posturography criteria.
      INTERVENTION: Vibrotactile head tilt feedback MAIN OUTCOME MEASURES: Change in
      Sensory Organization Test (SOT) Conditions 5 and 6 performance (fall-no fall,
      time to fall, strategy analysis) and dynamic subjective visual vertical (DSVV)
      response. RESULTS: 1) Significant improvement in binary fall-no fall ratio on SOT
      5 and SOT 6 combined (chi2 = 9.603, df = 1, p = 0.001); 2) Significant increase
      in time to fall measurements on SOT 5 (p < 0.001) and SOT 6 (p < 0.01; 1-tailed t
      test); 3) Nonsignificant improvement in strategy scores on SOT 5 (p = 0.156) and
      SOT 6 (p = 0.259; 1-tailed t test); and 4) No significant effect during eccentric
      DSVV testing (analysis of variance). CONCLUSION: Head-mounted vibrotactile
      stimulation produced significant improvement in postural stability in subjects
      with BVL undergoing SOT 5 and 6 testing with no effect on subjective visual
      vertical during DSVV testing.

PMID- 19106769
TI  - Speech recognition in cochlear implant recipients: comparison of standard HiRes
      and HiRes 120 sound processing.
AB  - OBJECTIVE: HiRes (HR) 120 is a sound-processing strategy purported to offer an
      increase in the precision of frequency-to-place mapping through the use of
      current steering. This within-subject study was designed to compare speech
      recognition as well as music and sound quality ratings for HR and HR 120
      processing. SETTING: Cochlear implant/tertiary referral center. SUBJECTS: Eight
      postlinguistically deafened adults implanted with an Advanced Bionics CII or HR
      90K cochlear implant. STUDY DESIGN/MAIN OUTCOME MEASURES: Performance with HR and
      HR 120 was assessed during 4 test sessions with a battery of measures including
      monosyllabic words, sentences in quiet and in noise, and ratings of sound quality
      and musical passages. RESULTS: Compared with HR, speech recognition results in
      adult cochlear implant recipients revealed small but significant improvements
      with HR 120 for single syllable words and for 2 of 3 sentence recognition
      measures in noise. Both easy and more difficult sentence material presented in
      quiet were not significantly different between strategies. Additionally, music
      quality ratings were significantly better for HR 120 than for HR, and 7 of 8
      subjects preferred HR 120 over HR for listening in everyday life. CONCLUSION: HR
      120 may offer equivalent or improved benefit to patients compared with HR.
      Differences in performance on test measures between strategies are dependent on
      speech recognition materials and listening conditions.

PMID- 19106770
TI  - Traumatic intravestibular luxation of the stapes highlighted by computed
      tomographic scan oblique multiplanar reconstructions.

PMID- 19106771
TI  - Chronic hereditary pancreatitis in a girl with a serine protease inhibitor kazal
      type I (SPINK-1) gene mutation and a coxsackie type B5 infection.

PMID- 19106772
TI  - Genetic diversity of the host and severe respiratory syncytial virus-induced
      lower respiratory tract infection.
AB  - Respiratory syncytial virus (RSV)-induced lower respiratory tract disease is a
      common problem in children and adults in Western societies. The clinical range of
      RSV infection from asymptomatic to respiratory distress syndrome is believed to
      be the outcome of viral and host immunity interactions. Genes associated with
      immune response are of particular interest regarding genetic predisposition to
      severe RSV infection. Several investigators have sought to identify genetic
      markers for high-risk patients, and more than 20 independent studies in the
      medical literature assess the impact of genetic variations-mostly single
      nucleotide polymorphisms-on the clinical presentation of RSV-induced disease.
      Several candidate gene loci have been tested in association studies based on the
      concept that a particular allele is a significant risk factor for a phenotype of
      interest. Despite the wealth of information available, we are still far from
      evolving a practical and cost-effective screening tool; certain flaws in
      association studies first need to be overcome. The development of haplotype-based
      analysis for candidate loci across the genome, along with advances in
      biostatistics and bioinformatics, would facilitate the assessment of the relative
      contribution of genetic markers to disease susceptibility in RSV infection.

PMID- 19106773
TI  - Helicobacter pylori infection in young children detected by a monoclonal stool
      antigen immunoassay.
AB  - The prevalence of Helicobacter pylori infection in young children attending day
      care facilities was studied using a monoclonal stool antigen test. Of 316
      samples, 78 (24.7%) were positive. Only 7/98 (7.1%) of the 3- to 12-month-old
      infants tested positive compared with 71/218 (32.5%) of the 13- to 60-month-old
      group. We conclude that approximately 30% of infants may become infected with H.
      pylori after the first year of life.

PMID- 19106774
TI  - Pharyngeal colonization by Kingella kingae in children with invasive disease.
AB  - Kingella kingae organisms isolated from the blood of 3 children with invasive
      infections were identical by pulsed field gel electrophoresis and random
      amplified polymorphic DNA-polymerase chain reaction analysis to those recovered
      from the patients' pharynx, demonstrating the likely role of upper respiratory
      tract colonization in the pathogenesis of the disease caused by this bacterium.

PMID- 19106775
TI  - Congenital measles caused by transplacental infection.
AB  - We report the case of a male infant born to a mother diagnosed as having measles
      before delivery. Although he was given standard immunoglobulin soon after
      delivery, he developed congenital measles. The diagnosis was confirmed by
      serology and PCR assay from the infant's pharyngeal secretions.

PMID- 19106776
TI  - Resistance of nasopharyngeal pathogens and antimicrobial prescription rates for
      children in an area under controlled antimicrobial use.
AB  - BACKGROUND: To reduce the spread of drug-resistant pathogens, appropriate use of
      antimicrobials is an indispensable measure. From January 2002, we undertook
      campaigns about antimicrobial treatment in Sado Island, Japan. METHODS: The
      subjects were born in 1996 (group-1996) or during 2002-2004 (group-2002-2004) and
      received outpatient treatment at our hospital. We evaluated the subjects' medical
      information from patient records during their first 3 years of life. Demographic
      data, duration of breast-feeding, and attending a day-care center (DCC) were
      evaluated using a questionnaire. RESULTS: Average visit-based antimicrobial
      prescription rates significantly decreased from 535 for group-1996, to 70 for
      group-2002-2004 per 1000 hospital visits (P < 0.001). The rate of cephalosporin
      prescriptions significantly decreased (77.1%-16.7%; P < 0.001), while amoxicillin
      (0.8%-29.5%) and macrolides (21.0%-52.4%) significantly increased (P < 0.001).
      Regarding 417 nasopharyngeal cultures from group-2002-2004, 77.8% (179/230) of
      Streptococcus pneumoniae strains were nonsusceptible to penicillin. For
      Haemophilus influenzae strains, 30.6% (59/193) were nonsusceptible to ampicillin.
      Living with older sibling(s) and early DCC attendance were associated with
      carriage of resistant pathogens. CONCLUSIONS: In a closed area under controlled
      antimicrobial use, our data indicated that decreasing antimicrobial prescriptions
      alone could not achieve elimination of resistant pathogens. Strategies to control
      transmission at DCCs or from older sibling(s) are also essential.

PMID- 19106777
TI  - Necrotizing epiglottitis in an infant: an unusual first presentation of human
      immunodeficiency virus infection.
AB  - We describe the case of a 4-month-old infant presenting with severe respiratory
      distress secondary to necrotizing epiglottitis, who was subsequently diagnosed
      with human immunodeficiency virus infection. Additionally, we review the existing
      literature on this rare condition with a focus on the potential underlying
      pathogenesis.

PMID- 19106778
TI  - Acute retinal necrosis in primary herpes simplex virus type I infection.
AB  - Here we report the case of an immunocompetent 8-year-old child who developed
      acute retinal necrosis concomitant with a primary herpes simplex virus type I
      infection. Ocular inflammation changed along with the development of a specific
      antibody titer in the serum. This evidence suggests that the immune response of
      the host can significantly modulate the clinical aspect of the ocular infection.

PMID- 19106779
TI  - Steady-state pharmacokinetics of lopinavir/ritonavir in combination with
      efavirenz in human immunodeficiency virus-infected pediatric patients.
AB  - The pharmacokinetics of lopinavir/ritonavir (LPV/RTV) 300 mg/m twice daily and
      efavirenz (EFV) 350 mg/m once daily were evaluated in HIV-infected children. The
      minimum concentrations for LPV contained values above the target range, and the
      estimated minimum concentrations for EFV contained values below the range. Our
      data support the current LPV/RTV dose, but EFV 350 mg/m may not be sufficient.

PMID- 19106780
TI  - Pertussis vaccine effectiveness after mass immunization of high school students
      in Australia.
AB  - Vaccine effectiveness in the first large-scale use of adolescent pertussis
      vaccine in Australia was evaluated by the screening method. Vaccine effectiveness
      was 78.0% (95% CI: 60.7-87.6%) for all study cases (n = 167), increasing to 85.4%
      (95% CI: 83.0-87.5%) for laboratory-confirmed cases (n = 155). Effectiveness
      should be comparable in settings with similar programs, such as the United States
      and Canada.

PMID- 19106781
TI  - Multiple relapses of visceral leishmaniasis in an adolescent with idiopathic CD4+
      lymphocytopenia associated with novel immunophenotypic and molecular features.
AB  - An adolescent with idiopathic CD4 lymphocytopenia suffered from 4 visceral
      leishmaniasis relapses despite appropriate treatment. CD8 lymphocytopenia and
      abnormal expansion of TCRalphabeta, CD4, CD8 cells were consistently detected
      together with reduced export of mature T cells from thymus. This novel form of
      idiopathic CD4 lymphocytopenia may predispose to multiple visceral leishmaniasis
      relapses.

PMID- 19106782
TI  - Association of the dopamine D3 receptor Ser9Gly and of the serotonin 2C receptor
      gene polymorphisms with tardive dyskinesia in Greeks with chronic schizophrenic
      disorder.

PMID- 19106783
TI  - Muscle activation strategies in multiple muscle systems.
AB  - Multiple neural and mechanical factors need to be taken into account to
      understand muscle activation strategies during human movement. These factors
      include lateral force transmission via connective tissue, summation of forces
      across a joint, tendon compliance that influences muscle shortening/lengthening,
      and the activity of biarticular muscles that influences activation strategies in
      monoarticular muscles. The relevance of these factors to muscle activation
      strategy in multiple muscle systems is introduced.

PMID- 19106784
TI  - Eccentric training and the science behind.

PMID- 19106793
TI  - MRI prediction of therapeutic response to epidural steroid injection in patients
      with cervical radiculopathy.
AB  - OBJECTIVE: To analyze whether magnetic resonance imaging (MRI) findings can be
      used to predict therapeutic responses to cervical epidural steroid injections
      (CESI) in patients with cervical radiculopathy. DESIGN: Retrospective single
      center study. Patients were categorized by presence or absence of four types of
      cervical MRI findings (disk herniation, nerve root compromise, neuroforaminal
      stenosis, and central canal stenosis). Thus, for each of the four types of MRI
      findings, there was a positive-MRI arm and a negative-MRI arm. Severities of
      these MRI findings were also noted. The treatment outcome variable was the change
      in Neck Disability Index (NDI) score after CESI. For each of the four MRI finding
      types, t test was done to see if there was any significant difference in the
      outcome between positive-MRI arm and negative-MRI arm. Then, we repeated the same
      analyses after adjusting the arms to include only those of "major" radiologic
      severity in the positive-MRI arms. RESULTS: After inclusion and exclusion
      criteria were applied, 32 patients were included. Only the presence, vs. absence,
      of central canal stenosis was associated with significantly superior therapeutic
      response to CESI (mean NDI improvement of 14.14 in positive-MRI arm, vs. mean NDI
      worsening of 2.11 in negative-MRI arm; P = 0.012). After controlling for other
      MRI finding types, the statistical significance still held for central canal
      stenosis (beta = -0.438; P = 0.022). When only the patients with MRI findings of
      major severities were considered as positive results, central canal stenosis was
      still the only finding type associated with significantly superior outcome (mean
      NDI improvement of 23.00 in positive-MRI arm, vs. mean NDI improvement of 0.85 in
      negative-MRI arm; P = 0.002). Controlling for other MRI finding types, the
      statistical significance still held for central canal stenosis (beta = -0.534; P
      = 0.002). CONCLUSIONS: Patients with central canal stenosis achieved
      significantly better functional outcome after CESI than those without. Hence, the
      MRI finding of central canal stenosis is a potential indication that CESI may be
      merited.

PMID- 19106794
TI  - Reliability and validity of the Manual Function Test in patients with stroke.
AB  - OBJECTIVE: The Manual Function test (MFT) is an upper-limb function assessment
      measure for hemiparetic patients after stroke. This study represents the
      reliability and validity of the MFT. DESIGN: Ninety patients within half a year
      after stroke onset were hospitalized from August 2005 through November 2006. Test
      retest reliability, interrater reliability, and internal consistency reliability
      of MFT were investigated. Validity of the MFT was evaluated with the Brunnstrom
      Stage, the Stroke Impairment Assessment Set, and the Barthel Index. RESULTS: The
      test-retest reliability coefficient and interrater reliability of the MFT were
      consistently above 0.95. Cronbach's alpha coefficient as internal consistency of
      eight items was also 0.95. With respect to the validity of the MFT, it had a
      correlation of >0.8 with both the Brunnstrom Stage and the Stroke Impairment
      Assessment Set. The correlation among task items within each category was also
      high. There was a higher correlation (rho = 0.647) between the MFT and Barthel
      Index. Among the Barthel Index items, "dressing" had the highest correlation with
      the MFT, which indicates that upper-limb functions and degree of independence in
      dressing are highly correlated. CONCLUSIONS: It was concluded that the MFT offers
      reliable and valid methods for assessing for upper-limb functional disorders.

PMID- 19106796
TI  - Obstructive coronary artery disease in high-risk diabetic patients with and
      without atrial fibrillation.
AB  - OBJECTIVE: To investigate the severity of coronary artery disease by coronary
      angiography in age-matched and sex-matched patients with diabetes mellitus with
      atrial fibrillation versus sinus rhythm. METHODS: The patients included 245 men
      and women, mean age of 70 years, with diabetes and atrial fibrillation and 245
      age-matched and sex-matched patients with diabetes and sinus rhythm who underwent
      coronary angiography. Baseline characteristics and indications for coronary
      angiography were similar in both groups. RESULTS: Greater than 50% narrowing of
      one, two, or three major coronary arteries were present in 229 of 245 patients
      (94%) with diabetes and atrial fibrillation and in 211 of 245 patients (86%) with
      diabetes and with sinus rhythm (P<0.01). Greater than 50% narrowing of three
      major coronary arteries were present in 150 of 245 patients (61%) with diabetes
      and atrial fibrillation and in 75 of 245 patients (31%) with diabetes and sinus
      rhythm (P<0.001). CONCLUSION: Patients with diabetes and atrial fibrillation have
      a significantly higher prevalence of greater than 50% narrowing of one or more
      major coronary arteries and of three major coronary arteries than patients with
      diabetes and sinus rhythm.

PMID- 19106795
TI  - Is lowering blood pressure hazardous in patients with significant ipsilateral
      carotid stenosis and acute ischaemic stroke? Interim assessment in the 'Efficacy
      of Nitric Oxide in Stroke' trial.
AB  - BACKGROUND: High blood pressure (BP) in acute stroke patients is both common and
      associated with a poor outcome, although best management remains unclear.
      Particular uncertainty exists in patients with carotid stenosis in whom lowering
      BP might reduce cerebral perfusion and worsen outcome. METHODS: Efficacy of
      Nitric Oxide in Stroke (ENOS) is an international, randomized controlled trial
      investigating the effect of lowering BP with glyceryl trinitrate in 5000 patients
      with acute stroke. This analysis is based on patients with ischaemic stroke for
      whom information on the carotid status was available. Neurological impairment
      (Scandinavian Stroke Scale) and rate of recurrent stroke were assessed on day 7,
      and the functional outcome (modified Rankin score) was determined on day 90. ENOS
      is ongoing, therefore analyses are blinded to treatment. RESULTS: At the time of
      analysis, 565 patients with ischaemic stroke had been randomized into ENOS and
      data on carotid status were available in 394 (70%) of these patients. Ipsilateral
      stenosis > or =50% was present in 50 patients (13%). Six of 344 (2%, 95%
      confidence interval: 0.7, 4%) patients with ipsilateral stenosis <50% had a
      recurrent stroke by 7 days as compared with none of 50 patients (0%, 95%
      confidence interval: 0, 9%) (P=0.73) with stenosis > or =50%. No significant
      difference in impairment was present on day 7; mean Scandinavian Stroke Scale
      with stenosis 38.3 versus no stenosis 43.2 (P=0.48). Adjusted functional outcome
      after 90 days was worse in those with a baseline carotid stenosis > or =50%;
      median modified Rankin score 3.0 versus 2.0 (P=0.03). CONCLUSION: Interim data
      provide reassurance that it is reasonable to continue including patients with
      carotid stenosis into trials of acute BP lowering (such as ENOS).

PMID- 19106797
TI  - Role of ezetimibe in the management of patients with atherosclerosis.
AB  - Lowering low-density lipoprotein cholesterol is central to the management of
      patients at risk of atherosclerosis. Traditional treatment has focused on
      modifying the endogenous lipid pathway using statins. Ezetimibe, a selective
      inhibitor of cholesterol absorption, has proved to be highly effective in
      lowering low-density lipoprotein cholesterol, and its use has soared, especially
      in the United States. Unfortunately, there is currently no evidence proving that
      treatment with ezetimibe is linked to a reduction in cardiovascular events;
      therefore, its choice as a drug to lower cholesterol is currently controversial.

PMID- 19106798
TI  - Velocity propagation of early diastole is a valuable tool for left ventricular
      remodelling after the first myocardial infarction.
AB  - PURPOSE: Velocity propagation (Vp) of early diastole is a known method for the
      evaluation of left ventricular (LV) diastolic function. Our purpose was to
      determine whether Vp is a valuable tool to characterize patients after acute
      myocardial infarction and LV remodelling (LVR). METHODS: M-mode, two-dimensional
      and Doppler echocardiography were performed in 71 patients within the first 2
      days, 1, 3 and 6 months after acute myocardial infarction. We measured the left
      atrium, LV diameters and volumes, peak early and late velocity (E, A)
      deceleration time, Vp, annular velocity (e) and calculated E/e. The patients were
      divided in two groups: (A) without early LVR (n=39) and (B) with early LVR
      (n=32). RESULTS: In the first evaluation, Vp was similar in both groups (36.37
      vs. 35.49 cm/s, P=0.513). Late LVR (LLVR) (44%) had developed in patients from
      group A with significantly lower early Vp compared with patients without LLVR
      (31.52 vs. 40.12 cm/s, P=0.001), with persist values even after 6 months (29.41
      vs. 40.85 cm/s, P=0.001). The values of Vp were similar in the first 2 days in
      patients from group B with developing (78%) and nondeveloping LLVR (35.29 vs.
      36.60 cm/s, P=0.614). Differences became significant after 6 months (31.71 vs.
      41.80 cm/s, P=0.001). The values of Vp of 35 cm/s or less from the first week in
      both groups correlated with LLVR (B=3.27, P=0.015). Changing of LV volumes
      significantly correlated with Vp; for end-diastolic volume/body surface area
      (r=0.21, P=0.041) and end-systolic volume/body surface area (r=0.30, P=0.014).
      CONCLUSION: In this study, Vp was the only valuable Doppler echocardiographic
      tool that reflected early LVR and LLVR.

PMID- 19106799
TI  - Self-administered semiquantitative food frequency questionnaires: patterns,
      predictors, and interpretation of omitted items.
AB  - BACKGROUND: Food items on a self-administered food frequency questionnaire (FFQ)
      may be left blank because the food was not consumed, because of difficulties
      remembering the frequency or amount of intake, or due to an oversight. METHODS:
      We explored the predictors and frequency of consumption of omitted food items on
      an FFQ used in the Nurses' Health Study II. Of 87,676 women who returned a mailed
      147-item FFQ in 1999, 34% completed the entire questionnaire, whereas 66% left at
      least 1 food item blank. Ten or more food items were omitted by 5% of
      participants. Foods were more likely omitted by women who were older or more
      physically active. We resurveyed 2876 participants who had left between 1 and 70
      food items blank and asked them to fill in the blanks. Overall, 2485 participants
      provided complete responses. RESULTS: In the resurvey, 64% of the formerly
      omitted foods were marked as consumed never or less than once per month, 20% as 1
      to 3 times per month, 8% as once per week, and 9% as more than once per week.
      Commonly consumed foods and beverages were less likely omitted because they were
      not consumed than rarely consumed foods. The best estimate for the true intake
      value of an omitted food was 0.82 times the average population intake.
      CONCLUSIONS: While calculating nutrient intake, the assumption that items missing
      represent zero intake is reasonable. However, food items consumed more often in
      the population at large are less likely than rarely consumed food items to be
      left blank because they were not consumed.

PMID- 19106800
TI  - Self-reported confidence in recall as a predictor of validity and repeatability
      of physical activity questionnaire data.
AB  - BACKGROUND: Self-reported confidence ratings have been used in other research
      disciplines as a tool to assess data quality, and may be useful in epidemiologic
      studies. METHODS: We examined whether self-reported confidence in recall of
      physical activity was a predictor of the validity and retest reliability of
      physical activity measures from the European Prospective Investigation into
      Cancer and Nutrition (EPIC) past-year questionnaire and the International
      Physical Activity Questionnaire (IPAQ) last-7-day questionnaire.During 2005-2006
      in Sydney, Australia, 97 men and 80 women completed both questionnaires at
      baseline and at 10 months and wore an accelerometer as an objective comparison
      measure for three 7-day periods during the same timeframe. Participants rated
      their confidence in recalling physical activity for each question using a 5-point
      scale and were dichotomized at the median confidence value. RESULTS: Participants
      in the high-confidence group had higher validity and repeatability coefficients
      than those in the low-confidence group for most comparisons. The differences were
      most apparent for validity of IPAQ moderate activity: Spearman correlation rho =
      0.34 (95% confidence interval [CI] = 0.08 to 0.55) and 0.01 (-0.17 to 0.20) for
      high- and low-confidence groups, respectively; and repeatability of EPIC
      household activity: rho = 0.81 (0.72 to 0.87) and 0.63 (0.48 to 0.74),
      respectively, and IPAQ vigorous activity: rho = 0.58 (0.43 to 0.70) and 0.29
      (0.07 to 0.49), respectively. Women were less likely than men to report high
      recall confidence of past-year activity (adjusted odds ratio = 0.38; 0.18 to
      0.80). CONCLUSIONS: Confidence ratings could be useful as indicators of recall
      accuracy (ie, validity and repeatability) of physical activity measures, and
      possibly for detecting differential measurement error and identifying
      questionnaire items that require improvement.

PMID- 19106801
TI  - Risk factors for injury among high school football players.
AB  - BACKGROUND: Football is the most popular interscholastic high school sport in the
      United States. Prior research has described a higher rate of injury among high
      school football players than in other sports, but few studies have examined
      potential predictors while controlling for other risk factors. METHODS: Using a 2
      stage cluster sampling technique, we conducted a prospective cohort study from
      1996 to 1999 among varsity athletes from 12 sports in 100 North Carolina high
      schools. A total of 3323 football players participated. Injury exposure and risk
      factor data were collected by trained school personnel. Incidence rates, rate
      ratios, and odds ratios (ORs) were estimated using Poisson and logistic
      regression. RESULTS: There were 1064 injured athletes and 1238 injuries; 106
      injuries resulted in greater than 3 weeks lost from participation. The overall
      incidence rate was 3.54 per 1000 athlete-exposures (95% confidence interval [CI]
      = 3.31-3.78). The rate of game injury was 9 times that of practice injury (OR =
      9.2; 95% CI = 6.6-11). Athletes with a prior injury had twice the injury rate of
      those without (1.9; 1.5-2.4). Among those injured, having a coach with more
      experience, qualifications, and training was associated with half the odds of
      severe injury (0.49; 0.27-0.92). CONCLUSIONS: Prior injury, additional years of
      playing experience, and older age were predictors of injury incidence after
      controlling for multiple risk factors. A high level of coaching skills did not
      reduce the injury rate, but was protective against severe injury.

PMID- 19106802
TI  - Enchondral ossification of muscles of the calf: a case report on a new form of
      heterotopic ossification.
AB  - Enchondral ossification of two muscles of the calf is reported in a child. The
      ossified muscles were removed with good resultant function. This represents a new
      form of heterotopic ossification.

PMID- 19106803
TI  - Results of dorsal approach in surgical correction of congenital vertical talus:
      an Indian experience.
AB  - We present our experience in the correction of congenital vertical talus
      deformity in a single stage using dorsal approach. We operated on 20 feet using
      the dorsal approach and the average age of patients at the time of surgery was 16
      months. Talonavicular reduction was achieved in all the feet and there was
      significant improvement in postoperative talo-calcaneal and talo-first metatarsal
      angles, which were well maintained at a follow-up of 4 years. In conclusion, the
      dorsal approach efficiently manages the deformities of a congenital vertical
      talus foot and provides consistent radiological and clinical outcome with minimal
      complications such as revision surgeries and osteonecrosis of the talus.

PMID- 19106805
TI  - The antioxidant Cerebralcare Granule attenuates cerebral microcirculatory
      disturbance during ischemia-reperfusion injury.
AB  - Cerebralcare Granule (CG) is a compound Chinese medicine used for treatment of
      headache and dizziness associated with cerebrovascular diseases. To clarify the
      mechanism underlying the clinical outcome of CG, this study investigated the
      effects of CG on the structure and function of cerebral microvasculature during
      I/R injury. A total of 138 Mongolian gerbils were included and divided into four
      groups, each composed of 36 or 30 animals, for evaluating various parameters of
      concern. A skull window was prepared for microcirculatory observation in animals,
      which were subjected to I/R with or without pretreatment with CG (0.4 or 0.8
      g/kg). The velocity of red blood cells in the venules was observed by a high
      speed video camera system, along with intravital confocal microscopic
      measurements of microvascular diameters, adherent leukocytes, and albumin leakage
      in the brain cortex. Changes in the fluorescence intensity of dihydrorhodamine
      123 in cerebral microvessels and malondialdehyde level in the cortex were
      measured. The ultrastructure of the microvessels in the cerebral cortex was
      analyzed using both transmission and scanning electron microscopy. In addition,
      cerebral blood flow was monitored using the laser Doppler imaging technique.
      Pretreatment with CG (0.4 or 0.8 g/kg) significantly alleviated I/R injury
      induced disorders in cerebral microvasculature, as evidenced by the data observed
      at 60 min of reperfusion wherein the values in CG (0.4 g/kg) pretreatment group,
      CG (0.8 g/kg) pretreatment group, and I/R group were 2.43 +/- 0.24, 2.28 +/-
      0.18, and 6.00 +/- 0.35 for leukocyte adhesion, 2.51 +/- 0.40, 2.33 +/- 0.29, and
      4.77 +/- 0.24 for albumin leakage, 7.06 +/- 0.81, 5.93 +/- 0.42, and 28.38 +/-
      2.70 for dihydrorhodamine 123 fluorescence intensity in cerebral microvessels,
      16.35 +/- 0.52, 14.34 +/- 0.68, and 21.46 +/- 0.71 for malondialdehyde level in
      the cortex, and 0.43 +/- 0.07, 0.46 +/- 0.02, and 0.17 +/- 0.08 for cerebral
      blood flow, respectively. I/R injury-elicited ultrastructural alterations in
      microvessels in cerebral cortex were also mitigated impressively by CG
      administration, manifested as attenuation of the reduced number of opening
      capillaries and the altered fine structures in endothelium, which were
      characterized by rough inner surface, increased intracellular vesicles,
      hypertrophy of digitations of intercellular contact, and swollen perivascular
      astroglial processes. Cerebralcare Granule is able to attenuate I/R injury
      induced functional and structural changes in microvessels in the cerebral cortex
      of gerbils, an ability that is most likely correlated with its antioxidant
      potential.

PMID- 19106807
TI  - Rivastigmine reverses habituation memory impairment observed in sepsis survivor
      rats.
AB  - The objective of this study was to evaluate the rivastigmine effect on
      habituation to the open-field memory impairment observed in sepsis survivor rats.
      A prospective, controlled experiment was designed. The setting was an animal
      basic science laboratory, and the subjects were male Wistar rats weighing 300 to
      350 g. Rats underwent cecal ligation and puncture (CLP; sepsis group) with "basic
      support" (saline at 50 mL kg(-1) immediately and 12 h after CLP plus ceftriaxone
      at 30 mg kg(-1) and clindamycin at 25 mg kg(-1) 6, 12, and 18 h after CLP) or
      sham-operated (control group). Three days after surgery (1 week before the start
      the behavior procedure), treatment with rivastigmine was started. Ten days after
      surgery, animals were submitted to the habituation to an open-field memory test.
      In the test session, there was a significant reduction in both crossings and
      rearings in the sham and sepsis group that received rivastigmine when compared
      with the training, indicating memory acquisition. In contrast, in the sepsis
      group that did not receive rivastigmine there was no difference in crossings and
      rearings between training and test session, indicating an impairment in memory
      acquisition. Therefore, rivastigmine reversed cognitive impairment in sepsis
      survivor rats in the open-field test.

PMID- 19106808
TI  - Delay of LPS-induced acute lung injury resolution by soluble immune complexes is
      neutrophil dependent.
AB  - The pathophysiological role of soluble immune complexes (SICXs) and its
      relationship with neutrophils were investigated in LPS-induced acute lung injury
      (ALI) animal model (Sprague-Dawley rat) and through the in vitro studies. Results
      showed that LPS-induced SICX was timely related to changes of tumor necrosis
      factor alpha and macrophage inflammatory protein 2 (inflammatory cytokines) in
      bronchoalveolar lavage fluid. In vitro study showed that SICX can bind to Fc
      gammaR (CD64 and CD32 or CD16) to prevent the apoptosis of neutrophils. The SICX
      mediated apoptosis inhibition was extracellular signal-regulated kinase (ERK) or
      phosphoinositide 3 kinase dependent and was interrupted by PD98059 and LY294002.
      In vivo, additional amount of SICX exacerbated the lung injury caused by LPS. LPS
      induced lung injury and macrophage inflammatory protein 2 release, however, were
      prevented by CD64 and CD32 blockers (decoy antibodies). In conclusion, excessive
      amount of SICX in lung can act through Fc gammaRs to protect bronchoalveolar
      lavage fluid neutrophils from apoptosis that eventually lead to delayed
      resolution of ALI caused by LPS. Blockade of SICX engagement of CD32 and CD64
      (with decoy antibodies) could interrupt SICX-mediated protection of neutrophils
      and protect lung from LPS-induced injury. The decoy antibodies may therefore have
      therapeutic utility in ALI.

PMID- 19106809
TI  - TNF-alpha inhibits toll-like receptor 4 expression on monocytic cells via
      tristetraprolin during cardiopulmonary bypass.
AB  - Toll-like receptor 4 (TLR4) plays a major role in regulating the innate immune
      response, which is related to postoperative complications. Although inflammatory
      capacity and TNF-alpha synthesis were altered on monocytes after cardiopulmonary
      bypass (CPB), whether the CPB and the CPB-induced TNF-alpha affect TLR4
      expression on monocytes have not yet clarified. We speculate that the changing of
      TNF-alpha level during CPB may be involved in monocytic TLR4 expression. As
      previous report, our enzyme-linked immunosorbent assay showed that CPB elevated
      the plasma level of TNF-alpha, whereas off-pump cardiac surgery does not. Flow
      cytometry reported decreased levels of monocytic TLR4 in patients undergoing CPB
      but not undergoing off-pump cardiac surgery. To elucidate whether the CPB-induced
      TNF-alpha is related to TLR4 down-regulation, we used human monocytic THP-1
      cells. Actinomycin D chase experiments demonstrated that TNF-alpha decreased TLR4
      expression and TLR4 mRNA stability on THP-1. Confocal microscopy and real-time
      polymerase chain reaction showed that TNF-alpha induced intracellular
      tristetraprolin (TTP) expression. Transfection with TTP siRNA reversed the down
      regulation of TLR4 in TNF-alpha-stimulated THP-1. Treatment with ERK1/2 inhibitor
      and SAPK/JNK inhibitor decreased TNF-alpha-induced TTP expression.
      Immunoprecipitation and Western blot analysis showed that the TNF-alpha-mediated
      activation of TTP might be inhibited by p38 mitogen-activated protein kinase
      inhibitor and by PD98059. We also demonstrated in clinical samples with confocal
      microscopy and flow cytometry that CPB led to an elevation of TTP in monocytes.
      In conclusion, CPB and TNF-alpha decrease TLR4 expression on monocytes; TTP
      expression and mitogen-activated protein kinase-signaling pathways play critical
      roles in CPB- and TNF-alpha-mediated decreases of TLR4 on monocytes. Our results
      suggest that using TTP to control cytokine message decay rate may be a promising
      approach for controlling system inflammation and preventing post-CPB
      complications.

PMID- 19106810
TI  - Attenuation of the effects of rat hemorrhagic shock with a reperfusion injury
      inhibiting agent specific to mice.
AB  - Death after hemorrhagic shock (HS) may be caused by a generalized reperfusion
      injury, particularly noticeable in the gut. A period of tissue ischemia followed
      by reinstitution of perfusion produces severe inflammation that can be blocked in
      mice by preventing the binding of a pathogenic natural immunoglobulin M (IgM) of
      defined specificity to antigens in reperfused tissue by using a soluble peptide
      analogue of the IgM tissue target. We hypothesize that this agent can improve end
      points of rat HS: death, intestinal injury, and lung injury. Male Sprague-Dawley
      rats were anesthetized; 50% of calculated blood volume was removed for 120 min,
      shed blood, then returned; and animals were sacrificed at 72 h. One group of rats
      received i.v. analogue ([N2] 300 microg) with the return of shed blood. Small
      intestine and lung were evaluated by histological examination and
      immunohistochemistry. Lung edema was assessed by Evans blue extravasation and
      histological examination. I.v. N2 decreased experimental mortality from 62% to
      12% (P < 0.05). Associated with this was diminution of gut injury score from
      57.8% +/- 5.5% to 19.5% +/- 2.5% (P < 0.05), lung injury from 21.4 +/- 1.5 to
      14.8 +/- 1.3 polymorphonuclear leucocytes per high-power field x400 (P < 0.05),
      and Evans blue extravasation index from 0.61 +/- 0.14 to 0.18 +/- 0.06 (P <
      0.05). As well, the deposition of IgM and C3 that is seen in intestinal villi
      from HS was not present in N2-treated rats. The N2 peptide agent that blocks
      reperfusion injury in mice prevents death from rat HS, as well as attenuates gut
      reperfusion injury and its remote target injuries. These data suggest that death
      from HS is caused by reperfusion injury, and that an agent derived from mice is
      effective in rats when given in real therapeutic time.

PMID- 19106815
TI  - Inhibition of NF-kappaB activity prevents downregulation of alpha1-adrenergic
      receptors and circulatory failure during CLP-induced sepsis.
AB  - The reduced pressure response to norepinephrine during sepsis has directed our
      interest to the regulation of alpha1-adrenergic receptors. Because nuclear factor
      (NF)-kappaB occupies a prominent role in the inflammatory cascade, we
      hypothesized that NF-kappaB downregulates alpha1-receptors by liberation of
      proinflammatory cytokines and thereby contributes to septic circulatory failure.
      Sepsis was induced by cecal ligation and puncture (CLP) in wild-type mice and
      mice with deficiencies for proinflammatory cytokines, and mice were injected with
      TNF-alpha, IL-1beta, IFN-gamma, or IL-6. Animals were treated with
      glucocorticoids or small interfering RNA (siRNA) targeting multiple cytokines and
      NF-kappaB. Vascular smooth muscle cells were incubated with cytokines and calcium
      mobilization, mRNA stability assays, and promoter studies with alpha1-promoter
      luciferase constructs were performed. Cecal ligation and puncture treatment
      resulted in a hyperdynamic circulatory failure, diminished calcium response to
      norepinephrine, and a significant downregulation of alpha1-receptors.
      Proinflammatory cytokines also downregulated alpha1-receptors by suppressing
      promoter activity at the level of gene transcription. However, suppression of
      single proinflammatory cytokines in cytokine knockout mice did not diminish CLP
      induced downregulation of alpha1-receptors. In contrast, blocking multiple
      cytokines via siRNA pretreatment or glucocorticoid administration attenuated CLP
      induced cardiovascular failure and downregulation of alpha1-receptors.
      Furthermore, inhibiting NF-kappaB activity by siRNA reduced the production of
      cytokines, prevented circulatory failure and downregulation of alpha1-receptors,
      and improved survival of septic mice. Our findings indicate that NF-kappaB has a
      central role in augmenting proinflammatory cytokine production during sepsis,
      which in turn downregulates alpha1-receptor expression. Our data further define a
      critical role for NF-kappaB in the pathogenesis of septic shock, indicating that
      targeting NF-kappaB is a desired therapeutic strategy to treat septic vasoplegia.

PMID- 19106818
TI  - Evodiamine represses hypoxia-induced inflammatory proteins expression and hypoxia
      inducible factor 1alpha accumulation in RAW264.7.
AB  - Inflammation and low oxygen diffusion are recognized characteristics of
      cardiovascular diseases such as atherosclerosis. Evodiamine, extracted from the
      traditional Chinese herb, Evodia rutaecarpa, is a bioactive anti-inflammatory
      alkaloid. The objective of this study was to investigate whether evodiamine could
      repress hypoxia-induced inflammatory response. We showed that evodiamine
      repressed not only COX-2 and iNOS expression but also prostaglandin E2 release in
      a concentration-dependent manner under hypoxic conditions. Furthermore, our
      studies indicated that COX-2 mRNA was inhibited by evodiamine, implying that
      transcriptional activity is involved in the mechanistic pathway. It is striking
      that hypoxia-inducible factor 1alpha (HIF-1alpha) inhibitor, camptothecin,
      suppressed hypoxia-induced COX-2 expression rather than pyrrolidine
      dithiocarbamate, a nuclear factor kappaB inhibitor. In addition, our studies have
      confirmed that evodiamine inhibited HIF-1alpha, which accounted for the
      transcriptional activity of COX-2, rather than nuclear factor kappaB in RAW264.7
      cells. Finally, evodiamine did not affect either the level of HIF-1alpha mRNA or
      the degradation rate of HIF-1alpha protein, but it regulated the translational
      process of HIF-1alpha. We found that hypoxia-evoked phosphorylation of Akt and
      p70S6K was blocked after evodiamine treatment, in addition to the inhibition of
      phosphorylation of 4E-BP. These results suggest that the mechanism of repression
      of hypoxia-induced COX-2 expression by evodiamine is through the inhibition of
      HIF-1alpha at the translational level and is primarily mediated via
      dephosphorylation of Akt and p70S6K. Therefore, evodiamine could be an effective
      therapeutic agent against inflammatory diseases involving hypoxia.

PMID- 19106820
TI  - Endothelin-1 contributes to hemoglobin glutamer-200-mediated hepatocellular
      dysfunction after hemorrhagic shock.
AB  - Hemoglobin glutamer-200 (HbG) might be an alternative to human blood. However,
      artificial oxygen carriers are initially successful to restore oxygen supply but
      may induce organ dysfunction and increase mortality several days after
      application in terms of delayed side effects. Impairment of microcirculation and
      an inflammatory cytokine response through induction of endothelin (ET) 1 may
      contribute. We investigated the role of HbG for the therapy of hemorrhagic shock
      and for delayed side effects in a model of hemorrhagic shock and reperfusion
      (H/R). To analyze early effects, Sprague-Dawley rats (n = 8/group) were
      resuscitated after hemorrhagic shock (1 h) with shed blood or HbG followed by
      reperfusion (2 h). Hemorrhagic shock and reperfusion decreased liver
      microcirculation and hepatic function in both shock groups to the same extent.
      Thus, HbG was not superior to shed blood regarding resuscitation end points after
      hemorrhagic shock. To determine delayed effects, rats (n = 8/group) were
      pretreated with Ringer's solution (vehicle) or HbG (1 g/kg) 24 h before H/R.
      Endothelin receptors were blocked with bosentan. Subsequently, ET-1 expression,
      inflammatory response, sinusoidal perfusion, hepatocellular function (plasma
      disappearance rate of indocyanine green [PDRICG]), and redox state [NAD(P)H] were
      analyzed. After vehicle pretreatment, H/R increased ET-1, hepatocellular injury,
      NAD(P)H, and cytokine levels. Sinusoidal perfusion and PDRICG decreased. After
      HbG pretreatment, a further increase of ET-1 and hepatocellular injury was
      observed, whereas PDRICG further decreased. Application of bosentan after HbG but
      not after vehicle pretreatment significantly improved PDRICG and liver perfusion,
      whereas NAD(P)H and hepatocellular injury decreased. Furthermore, cytokine
      release changed to an anti-inflammatory response. These data suggest an HbG
      dependent increase of ET-1, which may contribute to delayed side effects under
      shock conditions.

PMID- 19106822
TI  - Cardiac-specific expression of heat shock protein 27 attenuated endotoxin-induced
      cardiac dysfunction and mortality in mice through a PI3K/Akt-dependent mechanism.
AB  - Cardiac dysfunction is a major consequence of septic shock and may be responsible
      for the high mortality of sepsis. We have reported that transgenic mice with
      cardiac-specific overexpression of heat shock protein 27 (Hsp27 Tg) exhibited the
      protection against doxorubicin-induced cardiac dysfunction. We hypothesized that
      overexpression of Hsp27 will attenuate cardiac dysfunction during endotoxemia.
      Hsp27 Tg and age-matched wild-type (WT) mice were injected with LPS. Cardiac
      function was evaluated by echocardiography, survival rate was carefully
      monitored, and activities of signaling pathways were determined by immunoblot.
      LPS administration significantly decreased cardiac function in WT mice. In Hsp27
      Tg mice, LPS-induced cardiac dysfunction was significantly attenuated as
      evidenced by increased ejection fraction (27.3%) and fractional shortening
      (37.1%), respectively, compared with LPS-treated WT mice. Heat shock protein 27
      Tg mice were more resistant to LPS-induced mortality than WT. The levels of
      phospho-Akt and phospho-glycogen synthase kinase 3beta (phospho-GSK-3beta) in the
      myocardium were significantly increased in Hsp27 Tg mice compared with WT after
      LPS administration. Nuclear factor kappaB-binding activity was significantly
      decreased in Hsp27 Tg mice compared with WT mice after LPS challenge. Similar
      results were observed in in vitro studies using Hsp27-transfected rat
      cardiomyoblasts. Importantly, phosphoinositide 3-kinase inhibition abolished the
      protective effect of Hsp27 in LPS-induced cardiac dysfunction and mortality of
      endotoxemia. Our results suggest that Hsp27 plays an important role in
      attenuation of cardiac dysfunction and mortality in endotoxemia and that the
      mechanisms of the protection may involve activation of the PI3K/Akt signaling
      pathway.

PMID- 19106823
TI  - Recent progress of proteomics in critical illness.
AB  - Critical illness, such as sepsis or septic shock with multiple organ dysfunction
      syndrome, is the leading cause of morbidity and mortality in intensive care
      units. The complexity of critical illness requires a robust methodology to
      explore the underlying mechanisms. Proteomics represents a powerful postgenomic
      biotechnology used for simultaneous examination of a large number of proteins or
      the proteome. Recent progress in proteomic techniques allows thorough evaluation
      of molecular changes associated with critical illness, thereby permitting to
      identify novel biomarkers and therapeutic targets. This review provides an update
      on the recent progress and potential of rapidly evolving proteomics approach to
      facilitate new discoveries in the field of critical care medicine.

PMID- 19106824
TI  - [Evaluation of pelvic endometriosis: the role of MRI].

PMID- 19106825
TI  - [Impact of ethnicity in the evaluation of coronary artery calcifications as a
      risk factor of coronary events].

PMID- 19106826
TI  - [CT imaging features of mechanical aortic valvular prostheses and related
      complications].
AB  - Currently, multidetector row CT (MDCT) is routinely used for cardiac imaging,
      especially for detection of coronary artery disease and morphological and
      functional evaluation. Recent advances in MDCT with cardiac gating and improved
      spatial and temporal resolution allow non-invasive evaluation of cardiac valves
      with significant reduction in artifacts traditionally associated with valvular
      prostheses. Postsurgical follow-up of mechanical aortic valvular prostheses
      requires knowledge of the functioning mechanism of different valve types and
      related complications, some potentially lethal and sometimes of insidious onset.
      The most frequently used non-invasive imaging modalities to evaluate morphology
      and function of prosthetic heart valves are echocardiography and fluoroscopy. We
      present the CT imaging features of three mechanical aortic valvular prostheses
      and the value of CT for diagnosis of related complications as a complement to
      standard imaging modalities.

PMID- 19106827
TI  - [MR imaging evaluation of endometrial carcinoma].
AB  - Prognosis for endometrial carcinoma is closely related to cell type and tumor
      grade but also to local staging using the FIGO classification. MRI, under
      specific technical conditions, allows excellent depiction of the degree of
      myometrial tumor extension. It also has an excellent specificity for the
      detection of cervical extension. In addition, it allows evaluation of regional
      nodes, but with sensitivity values that are not perfect. The purpose of this
      paper is to review the MR imaging features of endometrial carcinoma along with
      its limitations and pitfalls.

PMID- 19106828
TI  - [Early imaging features after sleeve gastrectomy].
AB  - PURPOSE: Sleeve gastrectomy is a new bariatric surgical procedure with promising
      early results and low morbidity and mortality. We have evaluated the early
      imaging findings and value of upper GI study (UGI) and CT. PATIENTS AND METHODS:
      Twenty five patients (mean age=38.9 years, mean BMI=51.5 kg/m2) following sleeve
      gastrectomy for morbid obesity underwent UGI at day 1. CT was immediately
      performed in patients with suspected leak or as a follow-up examinations in
      patients with suspected complication. The different imaging features observed
      were recorded. RESULTS: UGI demonstrated 13 normal examinations (52%), an
      abnormal appearance in 11 cases (44%) with opacification of a lateral pouch, and
      one complication (leak confirmed on CT). Two patients underweent CT (day 3 and
      day 15) for suspected complication, with demonstration of leak in both cases.
      CONCLUSION: An abnormal appearance after sleeve gastrectomy is frequently
      observed on UGI. Routine UGI at day 1 is useful to detect large leaks. CT with
      oral contrast should be performed in all patients with imaging or clinical
      suspicion of leak.

PMID- 19106829
TI  - [Pelvic trauma: impact of iodinated contrast material extravasation at MDCT on
      patient management].
AB  - PURPOSE: To determine the impact of iodinated contrast material extravasation at
      MDCT in selecting patients with pelvic fractures that require vascular
      embolization. PATIENTS AND METHODS: All patients with severe pelvic fracture
      admitted to the trauma unit between 1998 and 2004 underwent contrast enhanced
      MDCT prior to additional specific treatment. All patients with extravasation
      underwent immediate vascular embolization for hemodynamic stabilization.
      Orthopedic management was proposed when no contrast extravasation was
      demonstrated. The presence or absence of contrast extravasation on MDCT and the
      hemodynamic status of the patients were recorded. RESULTS: Seventy-four patients
      with pelvic fracture (mean age: 34 years) underwent contrast enhanced MDCT prior
      to therapeutic management. Vascular embolization was performed in 42 patients: 38
      showed contrast extravasation and 4 were in hemodynamic shock but showed no
      extravasation. Orthopedic management was performed in 27 patients after negative
      MDCT and 5 hemodynamically stable patients with positive MDCT. CONCLUSION: In our
      patient population, the presence of iodinated contrast material extravasation at
      MDCT was a determinant factor in the selection of patients for vascular
      embolization.

PMID- 19106830
TI  - [Role of contrast enhanced US in the evaluation of renal tumors].
AB  - PURPOSE: To evaluate the role of contrast enhanced US in the characterization of
      renal tumors. Materials and methods. Eighty-six renal tumors (33 solid, 53
      cystic) underwent contrast enhanced US after indeterminate CT/MRI (67 lesions) or
      US (19 lesions). Pathological correlation was available for 42 cases, and follow
      up at 3 and 6 months was available for 13 cases. Diagnosis was achieved in 21
      cases. Lesions included: 19 renal cell carcinomas (4 conventional, 14 papillary,
      1 tubulocystic), 5 oncocytomas, 3 metastases, 6 pseudomasses, and 53 cystic
      lesions including 6 malignant tumors. RESULTS: Solid tumors were correctly
      identified in 100% of cases. Characterization of solid tumors was possible with
      specificity of 92.9% for papillary carcinoma, 57.1% for clear cell carcinoma, and
      100% for oncocytoma. The specificity for distinguishing solid benign from solid
      malignant tumor was 100% based on the presence of hypoechogenicity relative to
      normal renal parenchyma on delayed imaging. Contrast enhanced US allowed
      reclassification of 23 indeterminate lesions on conventional US. It is of limited
      value for large cystic lesions or cystic lesions with extensive wall
      calcification. CONCLUSION: Contrast enhanced US is easily performed in clinical
      practice and allows improved characterization of some renal tumors compared to
      other cross sectional imaging techniques.

PMID- 19106831
TI  - [MR imaging features of deep pelvic endometriosis: correlation with laparoscopy].
AB  - Deep pelvic endometriosis is an invalidating disorder affecting the retrocervical
      region, rectosigmoid colon and urinary bladder generally requiring surgical
      management. MRI is the preoperative imaging modality of choice. The purpose of
      this paper is to describe the MR imaging features of deep pelvic endometriosis
      with laparoscopic correlation. METHODS: Thirty-five patients with clinical
      suspicion of deep pelvic endometriosis underwent pelvic MRI. Results of MRI,
      including morphological and signal characteristics features of the lesions were
      compared to laparoscopic fidings. RESULTS: Laparoscopy detected lesions of deep
      pelvic endometriosis of the uterosacral ligaments (n=10), torus uterinum (n=9),
      rectosigmoid (n=11), Douglas pouch (n=9), recto-vaginal septum (n=6), bladder
      (n=4) and posterior vaginal cul-de-sac (n=2). The sensitivity, specificity,
      positive predictive value and negative predictive value of MRI were assessed for
      each localization. CONCLUSION: MRI allows diagnosis of deep pelvic endometriosis
      of the bladder, rectosigmoid and Douglas pouch and with lower sensitivity for
      lesions of the uterosacral ligaments, posterior vaginal cul-de-sac and
      rectovaginal septum.

PMID- 19106832
TI  - [Imaging features of osteochondritis dissecans of the acetabulum: a case report].

PMID- 19106833
TI  - [Esophageal varices due to SVC thrombosis].

PMID- 19106834
TI  - [Intrathoracic gossypiboma thirthy years after thoracotomy].

PMID- 19106835
TI  - [Unusual lytic bone lesions in Caffey's disease].

PMID- 19106836
TI  - [Response to the September e-question. A trivial breast ganglion].

PMID- 19106839
TI  - [Imaging of thoraco-abdominal trauma].

PMID- 19106838
TI  - [Role of MRI in the presurgical work-up of breast cancer: appropriate utilization
      of MRI as a complement to mammography and ultrasound].
AB  - The role of MRI for presurgical local staging of breast cancers amenable to
      conservative treatment has been the subject of multiple publications and tends to
      become a "validated" indication in routine practice. The purpose of the paper is
      to review the advantages and limitations of this imaging modality that is part of
      a comprehensive management that must be validated by clinical data especially
      with regards to local recurrence and survival. Knowledge of these elements
      combined with more precise indications should result in improved patient
      management while avoiding overtreatment or unnecessary anxiety-producing
      examinations.

PMID- 19106840
TI  - [Chest trauma: spectrum of lesions].
AB  - Blunt chest trauma typically occurs as part of polytrauma, usually secondary to
      motor vehicle accidents, sports related injuries or defenestration in Western
      Europe. Each chest compartment may be responsible for immediate and/or delayed
      complications, thus requiring a dedicated systematic and comprehensive analysis.
      The use of image post-processing is mandatory in order to not overlook a
      potentially severe injury. The purpose of this paper is to review the technical
      considerations of multidetector CT, and the imaging features and interpretation
      method for each chest compartment, in order to generate an adapted report.

PMID- 19106841
TI  - [Abdominal trauma: spectrum of lesions].
AB  - Abdominal injuries are more often observed in the setting of polytrauma.
      Detection and accurate description of hemoperitoneum, solid organ injuries
      (contusion, hematoma, laceration, fracture), bowel perforation and arterial
      bleeding allow optimal multidisciplinary management. Mesenteric and bowel
      injuries are often difficult to diagnose and may be masked by the presence of
      more frequent injuries (spleen, liver). MDCT is the gold standard imaging
      modality for severe blunt abdominal trauma.

PMID- 19106842
TI  - [Trauma of the thoraco-abdominal area: imaging strategy].
AB  - The imaging work up of patients following trauma to the thorax and/or abdomen is
      dependent upon the hemodynamic and respiratory status. In patients with
      respiratory distress, management is based on a chest radiograph to detect pleural
      effusion or pneumothorax requiring immediate drainage. In patients with
      hemodynamic shock despite adequate resuscitation, FAST US may be the only imaging
      study performed, along with a chest radiograph, prior to laparotomy in the
      presence of hemoperitoneum. CT is the key to the management of patients with
      potentially severe trauma based on clinical findings and/or the nature of the
      trauma. CT analysis must be rigorous and exhaustive to detect lesions responsible
      for the clinical findings but also to identify dangerous lesions even if not
      currently symptomatic, such as contained isthmic aortic transection, bowel
      perforation or diaphragmatic injury. In patients with less severe trauma, the
      choice between chest radiographs and abdominal US, more economical, and with less
      radiation, and CT of the thorax and abdomen, more exhaustive and more accurate,
      will be discussed on a case by case analysis.

PMID- 19106843
TI  - [Interventional radiology and thoraco-abdomino-pelvic trauma].
AB  - Multidetector CT is very useful in the evaluation of polytrauma patients. MDCT is
      valuable for the detection and treatment planning of vascular injuries, but it
      may not be available to hemodynamically unstable patients. Embolization of
      visceral and parietal branches of the aorta benefits from advances in catheter
      technology: hydrophilic catheters and microcatheters are very helpful in this
      context. Resorbable particles (such as gelatin) and coils are the most useful
      occlusive agents. Endovascular stenting of aortic rupture is nowadays considered
      in many centers as the best therapeutic option and can be proposed as an
      alternative to surgery.

PMID- 19106844
TI  - [Thoracic and abdominal trauma in children].
AB  - Knowledge of the characteristics of thoraco-abdominal trauma in children is
      important to optimize the imaging work up while keeping radiation exposure to a
      minimum. Because of the plasticity of the pediatric rib cage, rib fractures are
      infrequent, and severe parenchymal injuries may be present in the absence of rib
      fracture. Mediastinal injuries are unusual. The increased mobility of solid
      intraabdominal organs combined with a weaker abdominal wall are specific to
      pediatric patients. First-line imaging typically includes chest radiograph and
      abdominal US with Doppler imaging. Contrast-material enhanced CT is used as a
      second-line technique, with delayed imaging in patients with urinary tract
      lesions. Dedicated pediatric acquisition protocols are mandatory. Follow-up is
      obtained mainly with US.

PMID- 19106845
TI  - [Determination of radiographic bone age for medico-legal purposes: looking for
      the best answer to this question].

PMID- 19106846
TI  - [MR imaging of the knees in patients over 50 years of age: incidental meniscal
      lesions].

PMID- 19106847
TI  - [Pain assessment and interventional spine radiology].
AB  - Due to advances in interventional spine procedures, the radiologist can now
      participate in the clinical evaluation of patients. The purpose of this article
      is to review the main tools available to evaluate spine related pain and promote
      their use to demonstrate the efficacy of different interventional spine
      procedures.

PMID- 19106848
TI  - [Linear or bubbly: a pictorial review of CT features of intestinal pneumatosis in
      adults].
AB  - Pneumatosis intestinalis is a rare condition, which is defined by the presence of
      gas within the bowel wall. In adult patients, pneumatosis intestinalis can be
      depicted in various circumstances. Owing to the routine use of CT to investigate
      patients with abdominal pain, pneumatosis intestinalis can be seen as an
      incidental finding or can be observed in association with a life-threatening
      disease such as bowel infarction. On CT images, pneumatosis intestinalis can
      display two different appearances; one that has a cystic or bubbly appearance can
      be considered as a chronic pneumatosis and is suggestive for a benign cause while
      the other, which has a linear appearance can be considered as a symptom and is
      more frequently secondary to a life-threatening cause. However, none of these two
      CT characteristics can be considered pathognomonic for any of these two
      categories of causes. In such situations, the analysis of the location, extent
      and, if any, associated findings may help to differentiate between benign and
      life-threatening causes. In these patients who present with abdominal signs that
      mimic symptoms that would warrant surgical exploration, the analysis of
      associated findings is critical to rule out a life-threatening cause of
      pneumatosis intestinalis and to obviate the need for unnecessary laparotomy. In
      adult patients with a known specific disease such as celiac disease, chronic
      pseudointestinal obstruction or other chronic diseases, even with accompanying
      pneumoperitoneum, pneumatosis intestinalis does not uniformly mandate surgical
      exploration. This pictorial review presents the more and the less common
      pneumatosis intestinalis CT features in adult patients, with the aim of making
      the reader more familiar with this potentially misleading sign.

PMID- 19106849
TI  - [Value of the sesamoid bone of the thumb in the determination of bone age].
AB  - PURPOSE: To assess the presence of ossification of the sesamoid bone of the thumb
      as a function of age and compare the results to data from the atlas by Greulich
      and Pyle describing the ossification of this bone in girls of 11 years and boys
      of 13 years. Materials and methods. Prospective study of 1372 children (780 boys
      and 592 girls between the ages of 0.4 and 19.7 years, mean age of 9.7 years) with
      known chronological age requiring radiographic evaluation of the wrist-hand after
      minor trauma. The presence of a sesamoid was analyzed by logistic regression
      using the method of probits. RESULTS: The minimum and maximum ages in our sample
      population were 10-15.1 years for boys and 8.8-15.2 years for girls. The P50
      value (method of probits) corresponded to the chronological age at which 50% of
      the population had a visible sesamoid. It was 12.1 years for boys and 10.2 years
      for girls. CONCLUSION: The timing of ossification of the sesamoid of the thumb is
      widely variable. Ossification of this sesamoid should not be used as a precise
      indicator when determining bone age using the atlas by Greulich and Pyle.

PMID- 19106850
TI  - [Uterine artery embolization with resorbable material prior to myomectomy].
AB  - PURPOSE: Fibroids are a frequent cause of gynecology referral. Myomectomy is a
      conservative treatment alternative. The main risk from this procedure is
      hemorrhage. The main objective of this study was to demonstrate the efficacy of
      preoperative uterine artery embolization with resorbable agents to reduce blood
      losses and facilitate myomectomy. Secondary objectives were to evaluate morbidity
      and subsequent fertility. PATIENTS AND METHODS: Retrospective study of 21
      patients with preoperative uterine artery embolization prior to myomectomy at the
      University Medical Center of Dijon over a 3 year period. RESULTS: Myomectomy
      after uterine artery embolization with resorbable agents was associated with only
      minimal blood loss. Mean preoperative and postoperative hemoglobin levels were
      comparable (p<0.0001). Uterine suturing was technically simpler. The number of
      resected fibroids (p=0.2824) and the presence of preoperative anemia (p=0.474)
      had no statistically significant impact on the duration of hospital stay. Uterine
      synechiae occurred in three patients after the procedure, and were easily
      treated. Two patients had normal subsequent pregnancies. CONCLUSION: Preoperative
      uterine artery embolization with resorbable agents was effective in reducing
      surgical blood losses. This technique reduces the number of hysterectomies and
      hemorrhagic complications (hematoma, infection, weaker scar tissue). It should be
      considered in patients wishing uterine preservation when the hemorrhagic risk is
      high. Its use in patients seeking subsequent pregnancy should be further assessed
      with larger series.

PMID- 19106851
TI  - [Value of radiographic evaluation of the second metacarpal in the determination
      of bone age].
AB  - PURPOSE: Age determination based on bone maturate evaluation is routinely used in
      forensic science and anthropology. The aim of this study was to purpose a
      quantitative method of age determination on the second metacarpal in a population
      of children and adolescents by measurements of the epiphyso-metaphysal ratio
      (REM) (epiphysal diameter divided by metaphysal diameter) and the cortical index
      (IC). MATERIAL: and methods. We evaluated the REM and the IC on 417 hand
      radiographs of 2 from aged 20-year-old children. RESULTS: The correlation between
      REM and age for males (R2=0.62; p<0.001) and females (R2=0.68; p<0.001) was a
      good and significant. The correlation between IC and age for males (R2=0.34;
      p<0.001) and females (R2=0.30; p<0.001) was also significant but poor.
      CONCLUSION: Measurement of IC should not be used for age assessment. Measurement
      of REM is simple, reproducible and poor X-ray exposing technique. It should be
      very useful for age determination.

PMID- 19106852
TI  - [Comparison of 2D and 3D techniques in the evaluation of global ventricular
      function on multidetector-row CT].
AB  - PURPOSE: To compare two methods of post processing cardiac CT data to measure
      global ventricular function. Materials and methods. Retrospective study where
      three readers measured the end-diastolic volume (EDV), end-systolic volume (ESV)
      and ejection fraction (EF) of the right (n=22) and left (n=44) ventricles, using
      a 2D method (extrapolated volumetric method, EVM) and a 3D method (direct
      volumetric method, DVM) after cardiac CT with retrospective ECG gating. Inter-
      and intraobserver agreement were calculated based on the intraclass correlation
      coefficient (ICC) with 95% confidence interval (CI95%), and results obtained with
      each method were compared using the student t test for paired samples. RESULTS:
      Inter- and intraobserver reproducibility were very good for both methods, with
      ICC ranging between 0.694 and 0.992, without significant difference. For the left
      ventricle, EDV, ESV and EF were 16653 ml, 8351 ml and 5415% for DVM et de 20361
      ml, 11558 ml and 4613% for EVM respectively. Right ventricular values were 15247
      ml, 7534 ml, 5013% and 17253 ml, 9940 ml, 439% (p<0,0001). CONCLUSION: The very
      good inter- and intraobserver reproducibility for both methods validate their use
      in clinical practice. Volume measurements with DVM are always inferior to volumes
      with EDM, with inverse relationship for EF measurements.

PMID- 19106853
TI  - [Uterine lipoleiomyoma: atypical MR imaging features].

PMID- 19106854
TI  - [Splenosis: value of MRI with injection of a superparamagnetic contrast agent].

PMID- 19106855
TI  - [Ileosigmoid knot: a surgical emergency].

PMID- 19106856
TI  - [Spontaneous thrombosis of a post-biopsy breast aneurysm].

PMID- 19106859
TI  - [At the mercy of hospital rate-setting].

PMID- 19106861
TI  - [Is the debate on mechanical bowel preparation, before colorectal surgery,
      over?].
AB  - The present "point of view" tries to assess the state of the art in 2008 on the
      role of mechanical bowel preparation before colorectal surgery. The case of bowel
      preparation has been questioned by several meta-analyses of small randomized
      trials, suggesting also its detrimental effect in terms of anastomotic leaks. In
      2007 two large trials were published and pooling their data suggested an
      increased risk of deep abscesses when bowel preparation was omitted. A further
      meta-analysis including all published data on this topic appeared useful. This
      meta-analysis included almost 5 000 patients and showed bowel preparation
      involves no benefit in terms of surgical site infections, with more infections
      after bowel preparation (Odds ratio 1.40 [1.05-1.87]). Sensitivity analysis
      showed an increased risk of abscesses when bowel preparation was omitted but this
      risk is not clinically relevant since the number needed to harm was as high as
      333 patients. In conclusion this meta-analysis including a huge number of
      patients does not confirm the detrimental effect of bowel preparation but did not
      show any benefit of it; these conclusions being valid only for colonic surgery,
      rectal surgery needing further studies.

PMID- 19106862
TI  - [Surgical management of primary esophageal motility disorders].
AB  - Primary esophageal motility disorders are rare, the most common diagnoses being
      achalasia and diffuse esophageal spasm. Treatment aims to alleviate symptoms and
      may be medical, endoscopic, or surgical. Achalasia is most commonly treated by
      pneumatic dilatation or by laparoscopic Heller cardiomyotomy. Pneumatic
      dilatation is effective in 60-80% of cases, but functional results deteriorate
      over time. Surgical treatment is indicated when endoscopic dilatation is
      contraindicated or has failed. Functional results after cardiomyotomy are
      satisfactory in 90% of cases and results appear to be stable over time. The need
      for an associated antireflux procedure and the type of fundoplication remain
      controversial. For diffuse esophageal spasm, extended esophageal myotomy has
      yielded satisfactory functional results, but surgical treatment should be
      reserved for selected patients with severe symptoms.

PMID- 19106863
TI  - [Safety and accuracy of surgical procedures: case law evolution].
AB  - Surgeons, like other doctors, practice their profession within a framework of
      contractual liability defined by statute in 1936. This established that the
      doctor was subject to a contractual obligation to provide appropriate and
      diligent care. Care and technical acts should conform to those which would have
      been provided by a prudent doctor within the standards of knowledge and practice
      of his field; care which deviates from this standard would be considered medical
      error or fault. This standard of care is referred to as "sound professional
      conduct". However, while not calling this basic principle into question, civil
      jurisdictions have progressively held surgeons liable whenever injury has
      occurred following surgical acts, without considering whether care deviates from
      sound professional conduct. Since 2000, judges have begun to attribute a
      requirement for absolute safety of results in cases where the surgeon had injured
      an organ unrelated to the planned operation. However it seems that the rare
      judgments given on this topic in the last 2-3 years have become less frequent.
      The creation of a compensation regime for medical accidents, via the law dated
      March 4, 2002, has contributed to this evolution. It is to be hoped that the
      flaws described in this system do not encourage jurisdictions to reconsider
      previous case law decisions.

PMID- 19106864
TI  - [No-fault medical accidents: review of two years' activity of the regional
      commission for the compensation of medical accidents of the Provence-Alpes-Cotes
      d'Azur region (PACA)].
AB  - Compensation for victims of medical accidents identified as no-fault medical
      accidents (NFMA) will be financed by national solidarity: this is a major and
      innovative feature of the Law of March 4, 2002 relative to Patients' Rights. In
      this review, we analyse the decisions of the regional commission on compensation
      of medical accidents in the Provence-Alpes-Cotes d'Azur (PACA) region of France
      in 2004 and 2005, and we attempt to identify the prevalence of certain surgical
      procedures liable to result in NFMA and to define the concept of "unintended
      consequences" in the context of state of health of the patient and the
      predictable course of the malady. We hope to improve the medical information
      given to the patient and thereby the overall quality of management. NFMA was
      acknowledged in 57 claims, about 10% of all those received by the commission
      during this period. Nearly half of the claims were within the competence of the
      commission because of the existence of serious sequelae (Permanent Partial
      Disability) in 47%. No typical profile of age or gender emerged in the patients
      with NFMA. The majority of cases occurred after surgical procedures, in
      particular gastrointestinal surgery and orthopaedic surgery; 91% were planned
      procedures. We did not identify increased risk related to any given type of
      surgery, particular disease condition, or precise anatomic region. Complications
      were those usually observed such as neurological complications in vascular
      surgery or perforations in gastrointestinal surgery. The interpretation of NFMA
      has undergone an evolution during this two-year period. In 2004, previous poor
      health status precluded acknowledgment of a medical accident, the argument being
      that there was a predisposition to the complication which occurred. In 2005,
      compensation was based on a reduced Partial Permanent Disability score compared
      to the patient's previous health status. This became a means of measuring the
      impact of the medical complication on an already predictably unfavorable clinical
      course without medical intervention, and the legal aspect of the "ineluctable
      nature" of this course.

PMID- 19106865
TI  - [Peritoneal mesothelioma: treatment with cytoreductive surgery combined with
      hyperthermic intraperitoneal chemotherapy].
AB  - Diffuse malignant peritoneal mesothelioma is a rare and lethal disease.
      Locoregional treatments combining cytoreductive surgery with hyperthermic
      intraperitoneal chemotherapy (HIPEC) seem to improve prognosis. METHODS:
      Cytoreductive surgery and HIPEC was performed in 22 patients at the Centre
      Hospitalier-Lyon Sud between 1989 and 2006. A retrospective analysis of survival
      was carried out to assess clinical and histological prognostic factors. RESULTS:
      Nineteen patients with diffuse malignant peritoneal mesothelioma were included
      (16 epithelial, 3 biphasic and 3 multicystic forms). Sixteen patients presented
      stage 3 or 4 peritoneal mesothelioma according to the Gilly classification.
      Optimal cytoreductive surgery was performed for 11 patients (complete macroscopic
      resection or residual tumor nodules less than 2.5mm). No post-operative deaths
      occurred but 9 patients (47%) presented grade III or IV post-operative
      complications. The overall median survival was 36.9 months; completeness of
      cytoreduction was the only significant prognostic factor. CONCLUSION:
      Cytoreductive surgery combined with HIPEC may improve the length of survival for
      patients with diffuse malignant peritoneal mesothelioma; such patients should be
      treated in specialized centers.

PMID- 19106866
TI  - [Pediatric non-Hodgkin's lymphoma: primary surgical management of patients
      presenting with abdominal symptoms. Recommendations of the Lymphoma Committee of
      the French Society to Combat Pediatric Cancers (SFCE)].
AB  - Over the past two decades, dramatic improvements in the treatment of children
      with Non-Hodgkin's Lymphoma have led to cure rates close to 90%, even in advanced
      stage disease. The most frequent localization is abdominal, where Burkitt or
      Burkitt-like subtypes are predominant. Initial management often occurs in the
      setting of a urgent surgical intervention where multiple complications may
      gravely threaten prognosis within days or even hours. The SFCE Lymphoma
      Committee's guidelines for optimal management include: 1) The diagnosis of
      lymphoma should be systematically evoked whenever the clinical context is not
      consistent with idiopathic intussusception, particularly in children over the age
      of 3 or when clinical and/or ultrasound findings are not typical; 2) Limited
      bowel resection should be performed only if it allows complete tumor removal and
      is technically simple without extensive dissection or risk of major
      complications; 3) If surgical resection is likely to be difficult, risky, or
      incomplete, surgery should be limited to sampling of peritoneal fluid and tumor;
      4) In all cases, adequate tissue should be obtained and sent to the pathology
      department in appropriate media Analysis of tumor material may require, in
      addition to histology and cytology, immunophenotyping, cytogenetics, and
      molecular biology studies in order to arrive at an accurate diagnosis and
      prognosis and to guide treatment choices.

PMID- 19106867
TI  - [The Main Gate Syndrome: a new format in mass-casualty victim "surge"
      management?].
AB  - INTRODUCTION: Recent suicide bombings pose the novel problem for Trauma Centers
      of the massive simultaneous arrival of many gravely wounded patients. METHODS: We
      report the experience of the French-German Military Trauma Group, a Level 2
      Trauma Center, in Afghanistan during the wave of suicide bombings in February
      2007. RESULTS: Fourteen casualties were received. A first triage was carried out
      by the U S Army Level I group prior to evacuation. A second surgical triage was
      carried out with systematic ultrasound exam. Four cases (ISS>25) were re
      categorized and underwent emergency surgical procedures. CONCLUSION: Suicide
      bombing in crowded locations near an evacuation hospital may overwhelm the
      medical resources of the receiving center. It has been referred to as "The Main
      Gate Syndrome." We introduced the novel concept of a semi-evacuation hospital or
      receiving center where a second surgical triage was carried out. These
      exceptional circumstances require open-minded flexibility, a tailored approach,
      and close cooperation between surgeons and anesthetists to share experience,
      opinions, and ideas. In the setting of mass casualties, emergency ultrasound exam
      was shown to be a valuable and effective tool by virtue of its mobility,
      reproducibility, and immediate results.

PMID- 19106868
TI  - [Division of the arcuate ligament for compressive stenosis of the celiac axis
      noted during a pancreaticoduodenectomy].

PMID- 19106869
TI  - [Endoscopic parathyroidectomy through a lateral approach].

PMID- 19106870
TI  - [Treatment of large midline ventral hernias by component separation or by retro
      muscular prosthetic graft].

PMID- 19106871
TI  - [Acute emphysematous cholecystitis: x-ray diagnosis].

PMID- 19106872
TI  - [An unusual esophageal foreign body].

PMID- 19106873
TI  - [An unusual complication of endoscopic sphincterotomy].

PMID- 19106874
TI  - [Neoplastic portal vein thrombosis and hepatic metastasis from colorectal cancer.
      A rare association].
AB  - It is rare for portal vein thrombosis to complicate colorectal liver metastases.
      However malignant portal vein thrombosis must be anticipated when considering
      hepatic resection. While this finding may influence long-term survival, it does
      not absolutely contraindicate hepatic resection. We report here a case of
      colorectal metastasis to the liver with associated macroscopic malignant portal
      vein thrombosis treated with hepatic resection; the patient is free from
      recurrence at 5-year follow-up.

PMID- 19106875
TI  - [Virilizing ovarian tumors in the menopausal patient].
AB  - Virilizing ovarian tumors are rare and can occur at any age. In postmenopausal
      women, they commonly present with signs of masculinization. These tumors should
      be suspected in any patient with virilization and high testosterone levels
      (>1ng/mL). Tumor localization is sometimes difficult. These tumors are usually
      benign; surgical resection is the accepted treatment. Masculinizing consequences
      of hormonal secretions may be managed by cosmetologic treatments which should not
      be overlooked.

PMID- 19106877
TI  - [The genesis of medical errors and the assessment of blame].

PMID- 19106878
TI  - [Peritoneal cystic mesothelioma: benign or malignant?].

PMID- 19106879
TI  - [Isolated ileal duplication with laparoscopic repair: a rare case].

PMID- 19106881
TI  - [Non-operative management of blunt splenic trauma in the adult].

PMID- 19106883
TI  - [How to avoid research misconduct - recommendations for surgeons].
AB  - Research misconduct is defined by the Royal College of Physicians of Edinburgh as
      any behaviour by a researcher, whether intentional or not, that fails to
      scrupulously respect high scientific and ethical standards. Various types of
      research misconduct include fabrication or falsification of data, plagiarism,
      problematic data presentation or analysis, failure to obtain ethical approval by
      a research ethics committee or to obtain the subject's informed consent,
      inappropriate claims of authorship, duplicated publication, and undisclosed
      conflicts of interest. These can result in patient injury, deterioration of the
      patient-physician relationship, loss of public trust in biomedical research, as
      well as pollution/degradation of the medical literature. Surgical research
      malfeasance has been underreported, and no practical guidelines for good research
      and publication have appeared to date in French surgical journals. In an attempt
      to uphold the scientific integrity of our profession, we discuss research
      misconduct and emphasise preventive measures and considerations for surgeons.

PMID- 19106884
TI  - [Construction of a neo-vagina by sigmoidocolpoplasty].
AB  - Construction of a neo-vagina by sigmoidocolpoplasty has been effective in the
      treatment of vaginal aplasia, a condition most commonly seen with the Mayer
      Rokitansky Syndrome. This article describes the surgical technique and principal
      complications, and reviews the literature to compare this technique with other
      methods of repair, particularly the Davydov technique.

PMID- 19106885
TI  - [Early improvement in Type 2 diabetes in obese patients following gastric bypass
      and bilio-pancreatic diversion: the role of the entero-insular axis].
AB  - Improvement in Type 2 diabetes is seen in 80-98% of obese diabetic patients who
      undergo gastric bypass or bilio-pancreatic diversion. This improvement is evident
      early after the operation before significant weight loss has occurred. Although
      numerous teams have extensively studied the physiology of this early post-bypass
      amelioration of type 2 diabetes, the exact mechanism of diabetes remission
      remains unclear. Studies have focused on changes in the entero-insular axis,
      which is mediated in part by the interaction of insulinotropic hormones GIP and
      GIP 1 on the beta islet cells of the pancreas. Other mechanisms which have been
      postulated focus on the adipo-insular axis; the actions of adiponectin and leptin
      seem to have an important role in insulin resistance but their action is weight
      loss dependent. Post-operative caloric restriction may also contribute to the
      early resolution of type 2 diabetes observed after gastric bypass and bilio-
      pancreatic diversion.

PMID- 19106886
TI  - [Non operative management of blunt splenic trauma in adults].
AB  - Nonoperative management of blunt splenic injury allows preservation of the immune
      function of the spleen while avoiding unnecessary laparotomy. The aim of our
      study was to evaluate the feasibility and the results of conservative management
      of adult blunt splenic trauma in the context of a developing country.
      Nonoperative management was proposed for 52 out of 62 patients with blunt splenic
      trauma treated at the Casablanca University Hospital, Morocco. Motor vehicle-road
      accidents (88%) were the most common etiology. Multiple trauma was present in 79%
      of the cases. 15% of the cases had hemodynamic instability. Ultrasonography was
      performed in 52 patients; it showed splenic contusion in 45 patients and
      subcapsular hematoma in 7 patients. CT scan showed splenic contusion in 11
      patients. Four cases ultimately required operative management with one death. Of
      the remaining 48 patients, 45 had an uneventful course with observation, but
      there were two deaths in the observation group.

PMID- 19106887
TI  - [Splenic trauma: predictive factors for failure of non-operative management].
AB  - INTRODUCTION: Non-operative management of blunt splenic injury in adults has been
      applied with increasing frequency. However, predictive criteria for successful
      non-operative management are still a matter of debate. METHODS: we
      retrospectively reviewed all cases of blunt splenic injury in adult patients from
      1997 to 2006. RESULTS: Of 190 patients with blunt splenic trauma (median age: 33
      years, range 16-98), 43.7% (n=83) underwent emergency surgical intervention
      (Group I), and 56.3% (n=105) of patients were admitted for conservative treatment
      of splenic trauma. Conservative treatment was successful in 76.6% (n=82) (Group
      II), while 23.4% (n=25) of patients required a laparotomy (Group III).
      Ultimately, 43.2% of patients were successfully managed non-operatively, and
      56.9% underwent laparotomy. Mechanism of injury was not significantly different
      among three groups. Group I patients presented significantly more frequently with
      hypovolemic shock (p<0.01), associated injuries (p<0.01), and high grade of
      splenic injury (p<0.01). All patients with active bleeding as evidenced by
      extravasation on CT scan, underwent exploratory laparotomy. Failure of non
      operative management increased significantly with splenic trauma grade (grade I
      (0%), grade II (22.6%), grade III (27.6%) and grade IV (40%), (p<0.01) and with
      quantity of hemoperitoneum (10.4% of patients with small, 22.2% of patient with
      moderate, and 47.8% with large hemoperitoneum). The median interval for
      conservative treatment failure was 3 days (range: 1-15). Splenic injuries were
      operatively controlled by splenectomy (91.6%) and splenorrhaphy (8.4%).
      CONCLUSION: Suitability of adult patients with blunt splenic injury for non
      operative management may be predicted at initial presentation, based on
      hemodynamic status and associated injuries. The quantity of hemoperitoneum and
      magnitude of splenic injury are predictive factors for failure of conservative
      treatment. Early definition of these factors may help identify those patients
      likely to be successfully treated without laparotomy.

PMID- 19106888
TI  - [Limited pancreatic resections for intraductal papillary mucinous neoplasm].
AB  - INTRODUCTION: For non-invasive intraductal papillary and mucinous neoplasm (IPMN)
      with limited extent, pancreaticoduodenectomy (PD) or distal pancreatectomy (DP)
      seem excessive due to the risk of pancreatic insufficiency. Enucleation (EN) or
      medial pancreatectomy (MP) are not commonly performed for IPMN. The aim of this
      study was to evaluate the feasibility and results of EN and MP for non-invasive
      IPMN. PATIENTS AND METHODS: Of 249 patients with IPMN, we attempted a limited
      resection in 50 (20%) EN (n=31) or MP (n=20) with routine intra-operative frozen
      section pathology. One attempted EN was converted to MP. Indications for surgery
      were pain/pancreatitis (44%), suspicion of main duct involvement (28%), mural
      nodules in branch duct (14%), branch duct>30 mm (8%) or suspicion of mucinous
      cystadenoma (6%). Follow-up clinical assessment and MRI were performed on a
      yearly basis. RESULTS: Of the 31 attempted enucleations, 5 (13%) were immediately
      converted (4 PD, 1 MP) due to technical reasons (n=3) or due to findings on
      frozen section (n=2). At definitive pathological examination (accuracy of frozen
      sectioning=98%), branch ducts were involved by mild (n=21), moderate (n=7) or
      high grade dysplasia (n=2). One patient underwent a double EN. Of 20 attempted
      medial pancreatectomies, 8 (40%) required additional segmental resection due to
      significant IPMN lesions at pancreatic margins; 3 of the additional resection
      margins were tumor-free, and 5 were involved by IPMN (4 conversions to PD or DP,
      one contra-indication to PD). Overall, 49 pancreatic margins were analyzed by
      frozen sectioning with 98% accuracy. Resected specimens of 16 MP showed
      involvement by mild (n=7), moderate (n=7) or high grade dysplasia (n=2). There
      was no postoperative mortality. Median length of stay was 21 and 30 days
      respectively after EN and MP. Pancreatic fistula rate was 54% and 81%
      respectively after EN and MP. Three patients underwent early re-operation for
      hemorrhage. Overall median follow-up was 24 months (3-121). All patients are
      alive, 2 patients (5%) have presented with recurrent pain and 4 have developed
      tumor recurrence on imaging follow-up (4/33=12%). Two patients (5%) developed de
      novo diabetes (one after EN combined with DP) and a third patient developed
      worsening of pre-existing diabetes plus exocrine insufficiency. No patient had
      surgery for recurrence. CONCLUSIONS: EN and MP are feasible for non-invasive
      IPMN. Their significant early morbidity is counterbalanced by low rates of both
      long-term functional disorders and tumor recurrence.

PMID- 19106889
TI  - [Prophylactic antibiotic use in gastro-intestinal surgery: an audit of current
      practice].
AB  - OBJECTIVE: To evaluate compliance with clinical guidelines on prophylactic
      antibiotic usage in gastro-intestinal surgery. MATERIAL AND METHODS: The medical
      charts of one hundred consecutive patients undergoing surgery in the last 6
      months of 2006 were analysed as to determine whether the use of prophylactic
      antibiotics was indicated. Compliance with the prophylactic antibiotic guidelines
      of the Toulouse teaching hospitals and the Societe Francaise d'Anesthesie et de
      Reanimation (SFAR) was examined; cases were analyzed by the criteria of the Haute
      Autorite en Sante for indication, type of antibiotic, time of administration, and
      duration of treatment. RESULTS: Antibiotic prophylaxis was prescribed in 58% of
      patients; there was an 85% compliance rate with the indication. Of those
      receiving antibiotic prophylaxis, the choice of antibiotic was appropriate in
      82.8%, but the timing of administration was in compliance in only 39.7%. Duration
      of antibiotic administration was excessive in 5 cases. The overall rate of
      compliance with guidelines was 42%. CONCLUSION: Prophylactic antibiotic
      guidelines were inadequately applied, especially regarding the timing of
      administration. Further systemic progress is needed to achieve compliance with
      guidelines and documentation of administration; such evaluations must be repeated
      on regular basis.

PMID- 19106890
TI  - [Laparoscopic proctectomy with hand-sewn colo-anal anastomosis for distal rectal
      cancer].

PMID- 19106891
TI  - [Laparoscopic Roux-en-Y jejuno-jejunostostomy].

PMID- 19106892
TI  - [Pancreaticoduodenectomy by a superior mesenteric artery first approach].

PMID- 19106893
TI  - [Acute appendicitis in a patient with intestinal malrotation: the importance of
      CT imaging].

PMID- 19106894
TI  - [Retroperitoneal gangrene from a perforated retrocecal appendicitis].

PMID- 19106896
TI  - [A most unusual foreign body in the cecum].
AB  - The authors report a rare complication of total hip replacement - the intrapelvic
      migration of a hip prosthesis resulting in a cecal fistula.

PMID- 19106898
TI  - [History of carotid artery surgery].

PMID- 19106895
TI  - [A serious late complication of non-operative management of splenic trauma:
      rupture of splenic artery aneurysm].
AB  - Over the last five past years, three patients required urgent operation in our
      institution for hemorrhagic shock after rupture of a post-traumatic splenic
      artery aneurysm. Those patients had undergone non- operative management (NOM) of
      grade III, IV (AAST classification) splenic injury 9, 13, and 22 months earlier.
      Two of them had a CT scan 30 days after initial trauma with no evidence of a
      developing splenic artery aneurysm. All three patients survived after proximal
      ligature of splenic artery and hemostatic splenectomy. Our experience with these
      three cases suggests that a delayed follow-up for patients at high risk is
      indicated in order to prevent this dramatic complication by early intervention.
      The modality of this follow-up should be determined by a prospective multicenter
      study.

PMID- 19106899
TI  - [Post-coital rupture of a splenic artery aneurysm].

PMID- 19106902
TI  - [Emphysema due to alpha 1 antitrypsin deficiency: an insufficient screening].

PMID- 19106903
TI  - [Levels of proof for guidelines. Report of the French Language Society of
      Pneumology].

PMID- 19106904
TI  - [Atopic dermatitis aggravates the allergic airways inflammation in acute viral
      bronchiolitis].
AB  - INTRODUCTION: Exhaled nitric oxide (FeNO) is a putative non-invasive marker of
      eosinophilic airway inflammation with a good predictive value for allergic asthma
      in preschool children. The aim of the present study was to compare FeNO after
      acute viral bronchiolitis (AVB) in children aged less than 2 years without atopic
      dermatitis (AD) vs those with atopic dermatitis, as well as children with AD
      without any history of AVB. METHODS: Forty-two children (mean age +/- SD: 12.3 +/
      5.2 months; range 5.0-23.5; sex-ratio M: F=1.3: 1) were included in this
      prospective study, > 8 wks after an episode of AVB. The patients' atopic status
      was assessed both by clinical phenotype and IgE- mediated response to inhaled
      and/or food allergens. FeNO (ppb) was measured off-line by the chemoluminescence
      method on samples obtained from gas collected in a balloon during tidal
      breathing. RESULTS: There was a significant difference between the AVB/AD (23.4
      +/- 14.3 ppb, n=15) vs the AVB without AD group (13.5 +/- 10. 1 ppb, n=13) or the
      AD without AVB group (11.0 +/- 8.3 ppb, n=14). Maternal feeding for more than 2
      months decreased FeNO by 50%. CONCLUSION: Atopic children below 2 years with AD
      produce more NO after AVB than non-atopic children or atopic children without any
      history of AVB. Maternal feeding decreases FeNO.

PMID- 19106905
TI  - [Economic impact of second- and third-line erlotinib treatment of non small-cell
      lung cancer].
AB  - OBJECTIVE: This study examined care consumption and management costs among
      patients who received second- or third-line oral erlotinib therapy for non small
      cell lung cancer (NSCLC). METHODS: The study involved two observational cohorts
      of NSCLC second- or third-line treated patients. In the first, patients received
      IV chemotherapy alone (233 patients), while patients in the second cohort,
      received oral erlotinib (166 patients). Only direct costs were taken into
      account. The analysis adopted the payer's perspective. RESULTS: The treatments
      lasted a similar length in the second- line setting (respectively 94,5+/-67,5 and
      105+/-79,4 days for the IV and erlotinib cohorts) but was significantly longer in
      the erlotinib cohort during third-line therapy (76.6+/-96.5 versus and 114.4+/
      74.5 days, p<0.008). In the erlotinib cohort, there were more women (p=0.023), a
      higher rate of adenocarcinoma (p=0.0043), a similar rate of conventional
      hospitalization, but less daycare clinics (p<0.001). The erlotinib cohort
      received significantly less antiemetic treatment (p<0.0001), erythropoietin
      stimulating agents (p<0.005) and G-CSF (p<0.001). Monthly management costs per
      patient in the IV and erlotinib cohorts were respectively 3126 +/-1904 and 2750+/
      1450 euros during second-line treatment, and 3026+/-1029 and 2823+/-1490 euros
      during third-line treatment (no significant difference). These results must be
      validated by prospective observational studies focusing on quality of life and
      the time spent in hospital.

PMID- 19106906
TI  - [Malignant pleural effusion as the presenting site of cancer: comparison with
      metastatic pleural effusions from known cancers].
AB  - INTRODUCTION: Few studies have focused on malignant pleural effusions as the
      presenting site of cancer. The aim of our study is to evaluate their proportion
      in the total number of malignant pleural effusions, to identify their causes and
      determine their prognosis. PATIENTS AND METHODS: Patients were selected
      retrospectively from the database of the Pathology Department of the University
      Hospital of Nantes (France), which contained only the patients in whom a
      diagnosis of malignant effusion was made as the result of cytology of pleural
      fluid or pleural biopsy, between January 1999 and December 2001. Pleural
      effusions as the presenting site of cancer (R group) and those metastatic from
      known cancer (C group) were identified by study of the clinical data. RESULTS: Of
      209 cases, the malignant effusion was presenting site of cancer in 85 patients.
      In this group (R), a male predominance was identified (sex-ratio 1.36 vs. 0.42 in
      group C, p<0.01). In order of frequency the causes were: lung cancer (31 cases),
      mesothelioma (18 cases), primary cancer unknown (15 cases), ovarian carcinoma (10
      cases), lymphoma (5 cases) and other carcinoma (2 cases). In men lung cancer was
      the leading cause (42.8%); and in women its frequency was the same as ovarian
      carcinoma (27.7%). The median survival of these patients was 6.5 months.
      CONCLUSION: Pleural effusions as the presenting site of cancer account for 41% of
      all malignant pleural effusions. Their causes are mainly lung cancer in men and
      lung and ovarian cancers in women.

PMID- 19106907
TI  - [Multiple extrapulmonary thoracic hydatidosis].
AB  - INTRODUCTION: Extrapulmonary intrathoracic hydatid cysts are unusual but they may
      be multiple, particularly during a secondary dissemination. With the aim to
      clarify the origins of this dissemination, we report our experience in the
      treatment of multiple thoracic extrapulmonary hydatidosis (MTEH). MATERIAL AND
      METHODS: Between January 1995 and December 2004, 41 patients were operated on for
      MTEH in our department. Chest roentgenogram and computed tomography were the main
      means of diagnosis. The treatment consisted of total surgical removal of the
      intact cysts. The approach was a postero-lateral thoracotomy (right in 29 cases,
      left in 8 cases, bilateral in 3 cases) and a median sternotomy in one case. All
      patients received complementary medical treatment with Albendazol. RESULTS: The
      MTEH was secondary to haematogenous dissemination in 6 patients (15%), to a
      hydatid cyst of the lung in 7 patients (17%) and to a hydatid cyst of the liver
      in 28 patients (68%). 75% of these patients had had a previous surgical
      intervention for hepatic cyst and 88% of them had diaphragm involvement. There
      were no deaths among our patients but the recurrence rate was 12%. CONCLUSION:
      Secondary intrathoracic extrapulmonary hydatidosis is generally seen among
      patients operated on for hydatid cyst of the liver. Necessary precautions must be
      taken at the time of surgery to avoid any intrathoracic dissemination.

PMID- 19106908
TI  - [Characteristics of the patients included in the French cohort of patients with
      emphysema caused by alpha-1 antitrypsin deficiency].
AB  - INTRODUCTION: Alpha-1 antitrypsin deficiency is associated with the occurrence of
      pulmonary emphysema. The aim of this study is to describe the characteristics of
      patients with alpha-1 antitrypsin deficiency associated pulmonary emphysema.
      METHODS: We describe a prospective cohort study including adult patients with
      alpha-1 antitrypsin deficiency associated pulmonary emphysema confirmed by CT
      scan living in France. Patients' clinical and functional characteristics, quality
      of life measures and management were recorded every 6 months during a five-year
      period. RESULTS: 201 patients were included from 56 centres between 2005 and
      2008. The characteristics of 110 patients have been analysed. Mean age was 50
      years (SD:11.8), 62.7% were males, 90% were tobacco smokers. The main functional
      results (% predicted) were: FEV1: 42.8 (19.6), CPT: 128.3 (21.7), CRF: 167.0
      (46.0), 6 minute walking distance (meters): 413 (130). 51 (46.4%) patients
      received augmentation therapy. Augmentation therapy was administered weekly
      (37.5%), twice a month (35.4%) or monthly (25.5%). Study centre was the only
      factor associated with the likelihood to received augmentation therapy.
      CONCLUSIONS: The clinical and functional characteristics as well as management of
      these patients varied markedly. There is a need for a standardization of the
      management of patients with alpha-1 antitrypsin deficiency associated pulmonary
      emphysema.

PMID- 19106909
TI  - [Nodular amyloidoma associated with primary pulmonary Malt lymphoma].
AB  - INTRODUCTION: Pulmonary amyloidoma is a nodular formation containing amyloid
      deposits, which can mimick a pulmonary carcinoma. Its etiologic diagnosis require
      the search of an underlying infectious disease, a connective tissue disorder or a
      lymphoma. CASE REPORT: We report the case of a 73 year old woman, asymptomatic,
      presenting an incidental pulmonary opacity in the left upper lobe, associated
      with hilar lymphadenopathies, positive on PET scan. The patient underwent a left
      superior lobectomy with mediastinal lymphadenectomy. Histologically, the nodule
      was composed of amylodosis deposits. It was surrounded by a dense lymphoid
      infiltrate. The phenotype (CD20+, CD5-, CD3-, CD23-) of the lymphoid cells, like
      the demonstration of a lambda light chain restriction permited to pose the
      diagnostic of pulmonary Malt lymphoma and to characterize the AL lambda type of
      the amyloidosis CONCLUSION: Association of amyloidoma and Malt lymphoma is a rare
      condition. The histologic diagnosis of lymphoma may be difficult in this case,
      the lymphomatous process being concealed by the volume of the amyloid mass.
      Therefore it is necessary in case of amyloidoma to search histological signs of
      Malt lymphoma and to confirm diagnosis by demonstrating a B clonality and a
      immunoglobulin light chains restriction.

PMID- 19106910
TI  - [Infection due to Mycobacterium malmoense in an immunocompetent patient].
AB  - INTRODUCTION: Mycobacterium malmoense (MM) is an atypical mycobacterium
      responsible for opportunistic infection. The clinical and radiological picture is
      non-specific. The infection develops most frequently in a dystrophic lung. CASE
      REPORT: A patient of 52 years was admitted with an extensive multifocal pneumonia
      which later proved to be due to infection with MM. Empirical treatment was
      started with the combination of rifampicin, isoniazid, pyrazinamide (rifater) and
      ethambutol (myambutol). Subsequently, cultures showed sensitivity to rifampicin,
      ethambutol, oxfloxacin, clarithromycin (MIC < 2 mg/l) and rifabutin (MIC < 0.5
      mg/l). More than two weeks after the start of treatment, material aspirated at
      fibroscopy showed the persistence of numerous acid-alcohol fast bacilli, an
      increase, compared with the original examination, from 5 to 25 per field on day
      2, to 20 to 100 per field on day 19. Despite the late addition of clarithromycin
      there was a progressive deterioration in the pulmonary condition. CONCLUSION:
      There is little correlation between the in vivo and in vitro sensitivities of MM
      to antibiotics. In our patient the progress was unfavourable, even though the
      mycobacterium was sensitive to the combination of antibiotics used, with the
      exception of isoniazid that was not tested. In vitro isoniazid does not seem to
      be active against MM. There is no consensus of opinion on the antibiotic
      treatment of MM infections.

PMID- 19106911
TI  - [Diffuse idiopathic pulmonary neuroendocrine cell hyperplasia: a rare
      preneoplastic condition].
AB  - Diffuse idiopathic pulmonary neuroendocrine cell hyperplasia (DIPNECH) is an
      uncommon preneoplastic condition, often associated with typical carcinoid
      tumours. The observations reported below concern two women, both suffering from
      chronic pulmonary symptoms. These patients underwent computed tomography that
      showed a solitary nodule in the first patient and multiple sub centimetre nodules
      in the second. In both cases histological studies of the pulmonary biopsies
      revealed: a proliferation of neuroendocrine cells dispersed in the bronchial and
      bronchiolar epithelium, more specifically superficial to the basement membrane;
      some tumourlets; a typical carcinoid tumour was also found in the first patient's
      biopsy. The choice of treatment remains difficult, mainly because the existing
      studies are restricted to small numbers of patients or isolated cases, a
      consequence of the low prevalence of this disease. Considering its slow
      evolution, management by long-term clinical, endoscopic and radiologic
      surveillance may be considered. If a carcinoid tumour is present or appears
      during the surveillance, the standard treatment is still surgical resection.

PMID- 19106912
TI  - [Augmentation therapy with alpha-1 antitrypsin: 20 year- follow-up of a deficient
      patient].
AB  - INTRODUCTION: Alpha one antitrypsin deficiency is a rare genetic disorder
      occurring principally in patients with the PiZZ phenotype. This deficiency can
      lead to pulmonary emphysema which impairs quality of life and which may progress
      to respiratory failure. The diagnosis is based on the presence of emphysema
      typically with a basal preponderance and airflow obstruction and is confirmed by
      measuring A1AT levels. A1AT replacement is the only specific therapy for this
      condition. OBSERVATION: We describe the 1st patient with A1AT deficiency treated
      in this way in France. The patient was 52 years old at the start of treatment
      with A1AT replacement, initially in hospital and then at their place of
      residence. Treatment was initiated in the context of progressive breathlessness,
      the presence of emphysema and confirmation of the biochemical deficit. The
      patient received 4 g of AIAT per week in combination with inhaled corticosteroids
      and ongoing physical rehabilitation. Follow up over 20 years has revealed a
      slowing in the decline in spirometric measurements. No problems with tolerating
      the treatment have been reported. CONCLUSION: In this clinical case replacement
      therapy appeared to show clinical benefits and was well tolerated.

PMID- 19106913
TI  - [A severe side effect of antitubercular therapy: pyrazinamide induced
      thrombocytopenia].
AB  - The haematological side effects of antitubercular drugs are not well known. We
      report the observation of a patient who received Rifater for the treatment of
      pulmonary tuberculosis. After one month of treatment, he developed an acute
      pulmonary infection, with neutropenia (1218/microl) and thrombocytopenia
      (109,000/microl), requiring suspension of his antitubercular drugs. After the
      reintroduction of he again developed thrombocytopenia (6,000/microl) associated
      with bleeding and required treatment with intravenous immunoglobulin. The
      introduction of a combination of moxifloxacin, isoniazid, pyrazinamide, and
      ethambutol was followed by a new relapse of the thrombocytopenia. Responsibility
      of pyrazinamide was then suspected and later confirmed by the evolution of
      platelet levels after stopping and reintroducing this antibiotic. This is the
      third reported case of pyrazinamide induced thrombocytopenia, whose frequency is
      probably underestimated because of the use of compound treatment.

PMID- 19106914
TI  - [Acute respiratory distress with radiological appearances of pseudomesothelioma].

PMID- 19106915
TI  - [Follicular bronchiolitis presenting in a cystic fibrosis patient 15 years after
      the initial diagnosis].

PMID- 19107011
TI  - [Orphan diseases: what's new since 2005?].

PMID- 19107012
TI  - [Should hyperinflation become the main concern when caring for COPD?].

PMID- 19107013
TI  - [Non invasive ventilation: our debt to Paul Sadoul. Introduction to the
      specification sheets for the ventilators dedicated to non invasive ventilation].

PMID- 19107014
TI  - [Noninvasive ventilation in palliative care and near the end of life].
AB  - INTRODUCTION: The occurrence of life threatening severe respiratory failure in
      patients with an incurable illness may be an indication for the use of
      noninvasive ventilation (NIV). STATE OF THE ART: Two approaches are associated
      with the use of NIV in palliative care settings. In the "palliative approach",
      NIV is proposed for patients with end stage of chronic respiratory failure and do
      not-tracheostomize orders as a ceiling of care. In the "palliative and probably
      curative" approach, NIV may help patients with do-not-intubate orders or to
      forego endotracheal intubation. This review provides some guidelines for
      clinicians responsible for patients with incurable illness, to help to guide and
      anticipate the medical management if acute respiratory failure (ARF) develops.
      CONCLUSIONS AND PERSPECTIVES: NIV may palliate symptoms in patients near the end
      of life. In the case of severe ARF in patients with do-not-intubate orders, NIV
      may avoid the need for endotracheal mechanical ventilation, most often in
      patients with COPD or cardiogenic pulmonary oedema. NIV may help some patients to
      forego endotracheal intubation. Future studies are needed to examine the
      attitudes of patients and families to this intervention.

PMID- 19107015
TI  - [Tuberculosis, anti-TNF agents and other immunosuppressants: evolution of
      preventitive strategies].
AB  - The occurrence of tuberculosis (TB) in patients treated with immunosuppressive
      drugs (ISD) is an old problem that has been highlighted by cases occurring in
      patients using anti-TNFalpha drugs. After a brief review of anti-tuberculosis
      immunity to highlight the immunosuppressant targets, we show how an
      epidemiological approach allows the control of risk in patients with drug-induced
      immunosuppression. The assessment and the control of this risk are usually
      complicated by underlying immunosuppressant disease, co-morbidities, associated
      drugs and local disease prevalence. Steroid therapy in systemic diseases and ISD
      protocols in graft rejection prevention illustrate this problem particularly
      well. The management strategy adopted to combat anti-TNF related tuberculosis in
      rheumatoid arthritis (RA) has allowed these biases to be avoided. The incidence
      of TB in RA has been recorded in some national databases (USA, Spain). A four
      fold increase was registered after the introduction of anti-TNF agents in 2001
      which could be considered as the true risk of the drug. Several national health
      agencies proposed guidelines to screen and prevent TB risk in these patients.
      Their effectiveness was confirmed by the incidence of TB returning the level
      prior to the introduction of these agents. Recommendations could be improved by
      using interferon-gamma screening tests and a better benefit/risk prophylaxis.
      They should be observed and if possible extended to new and other ISD.

PMID- 19107016
TI  - [When should patients be referred by the physician to the lung transplant team?
      Patient selection, indications, timing of referral and preparation for lung
      transplantation].
AB  - INTRODUCTION: Lung transplantation (LT) is accepted as a therapeutic option in a
      wide range of end stage lung diseases, with evidence supporting survival and
      quality of life benefits in transplant recipients. Appropriate patients who have
      good chance of survival with transplantation should be identified carefully.
      STATE OF THE ART: Four diagnoses account for approximately 80% of transplant
      recipients: chronic obstructive pulmonary disease, idiopathic pulmonary fibrosis,
      cystic fibrosis and alpha-1-antitrypsin deficiency emphysema. The aim of this
      review is to discuss the selection process of potential candidates and to assist
      physicians in referring these patients to a transplant team. The decision to
      refer patients for transplantation is difficult and depends on several parameters
      such as the results of transplantation, the referring physician's view of
      survival prospects with actual medical therapy according to the pathology, and
      also the patient's physical, nutritional and psychological status. The timing of
      listing patients remains a difficult decision which is imposed by both defined
      criteria and uncertain events such as the rapid worsening of the lung disease and
      the likely waiting time. PERSPECTIVES: The optimal modalities for pre-surgical
      rehabilitation programs and their postoperative impact should be evaluated.
      CONCLUSIONS: Careful selection of potential candidates for lung transplantation
      at the most appropriate time should lead to an improvement of survival of such
      patients.

PMID- 19107017
TI  - [Effects of smoking on the thyroid gland, digestive system, kidney and bone].
AB  - INTRODUCTION: In addition to being a major cardiovascular risk factor, smoking
      promotes or worsens thyroid, digestive, renal and bone diseases. BACKGROUND:
      Smoking is positively associated with hyperthyroidism. It is associated with
      Graves' disease and it especially increases the risk of the development of severe
      exophthalmos. In contrast, smoking might exert a protective action for thyroid
      carcinoma. Smoking increases the severity of hepatic lesions in patients with
      chronic hepatitis C. Smoking accelerates the progression of primary biliary
      cirrhosis and increases the risk of hepatocellular carcinoma. Smoking increases
      risk of both hyperplastic and adenomatous polyps. While Crohn's disease is
      associated with smoking, ulcerative colitis is largely a disease of non smokers.
      Smoking increases risk of development of both renal cell carcinoma and chronic
      nephropathies, particularly in types 1 and 2 diabetes. Smoking is a risk factor
      for decreased bone density and is associated with a significantly increased risk
      of fracture. Smoking is related to the development of rheumatoid arthritis and
      may adversely influence its severity. CONCLUSIONS: Smoking might be considered a
      risk factor for the development of several thyroid, digestive, renal and bone
      diseases. Consequently, smoking prevention and cessation programs must be
      strongly encouraged among the patients concerned.

PMID- 19107018
TI  - [Obstructive sleep apnoea syndrome (OSAS) in women: a specific entity?].
AB  - Despite a variable prevalence in the literature, OSAS is characterized by a
      higher frequency in men. This study involved a review of published data
      describing the impact of gender on features of OSAS. In women, OSAS seems to be
      associated with certain anatomical factors such as more significant obesity, a
      thinner oropharyngeal junction, a shorter uvula and reduced upper airway (UA)
      collapsibility, in comparison with men. Sleep related breathing disorders
      observed during pregnancy are more likely UA resistance syndrome than true OSAS,
      and are associated with severe fetal and maternal complications that could be
      improved by the use of nasal CPAP. Though OSAS symptoms are underestimated by
      women, the Epworth score as well as snoring are not influenced by gender. Gender
      does not seem to be a risk factor for increased mortality. Compliance with nasal
      CPAP is identical in both sexes, but oral appliance seem to be more effective in
      women. Further studies are needed to produce the required complementary data to
      confirm specific sex-related features in the diagnosis and treatment of OSAS.

PMID- 19107019
TI  - [Respiratory involvement in systemic lupus erythematosus].
AB  - Respiratory involvement in systemic lupus erythematosus (SLE) is not as well
      known as the cutaneous, rheumatological and renal manifestations. It occurs
      frequently but the diagnosis may be difficult because of the heterogeneity of the
      anatomical and clinical presentations. A precise diagnosis is crucial as new
      immunosuppressive drugs have considerably improved the prognosis. The pathology
      involves genetic, endocrine, environmental, pharmacological and immunological
      factors with a cytotoxic reaction of auto antibodies against complement, a
      circulating immune complex reaction and a hyperactivity of B lymphocytes.
      Respiratory involvement in SLE can be classified in 5 groups based on the
      anatomy: pleural involvement, infiltrating pneumonia (lymphoid interstitial
      pneumonia, bronchiolitis obliterans with organizing pneumonia and acute lupus
      pneumonitis), airways involvement (upper airways, bronchi), vascular involvement
      (pulmonary hypertension, acute reversible hypoxaemia, alveolar haemorrhage, and
      antiphospholipid syndrome), muscular and diaphragmatic involvement (shrinking
      lung syndrome). Treatment is based, depending upon the type of involvement and
      its severity, on steroids which may be combined with immunosuppressants and
      plasmapheresis.

PMID- 19107020
TI  - [Dynamic lung hyperinflation and its clinical implication in COPD].
AB  - Static lung hyperinflation is defined as the elevation of end- expiratory lung
      volume above its predicted value, with no increase in end-expiratory alveolar
      pressure, which remains equal to atmospheric pressure. Dynamic hyperinflation is
      the transient increase of this volume above the relaxation volume. In patients
      with COPD, dynamic hyperinflation is mainly determined by the mechanical
      properties of the respiratory system. Its measurement relies on plethysmography
      and, during exercise, inspiratory capacity. During exercise, dynamic
      hyperinflation attenuates expiratory flow limitation but increases the
      inspiratory loading and induces functional weakness of the diaphragm. It also has
      haemodynamic consequences and results in more rapid, shallow breathing and
      progressive reduction in dynamic lung compliance. These events explain exercise
      intolerance. Several approaches may help combat dynamic hyperinflation and its
      deleterious clinical effects: bronchodilators, hyperoxia, helium-oxygen mixtures,
      lung volume reduction surgery...

PMID- 19107021
TI  - [Bevacizumab and radiotherapy].

PMID- 19107022
TI  - [The educational director; assistance in running therapeutic patient education
      sessions. Using the example of cystic fibrosis].

PMID- 19107023
TI  - [Non-invasive ventilator I specification sheet].

PMID- 19107024
TI  - [Non-invasive ventilator II specification sheet].

PMID- 19107025
TI  - [Non-invasive ventilator III specification sheet].

PMID- 19107026
TI  - [Tobacco and cannabis. The French Language Society of Pneumology].

PMID- 19107027
TI  - [Pulmonary medicine and inhalant abuse].

PMID- 19107028
TI  - [Respiratory manifestations of marijuana smoking].

PMID- 19107029
TI  - [Diagnosis of lung cancer: an opportunity for smoking cessation?].

PMID- 19107030
TI  - [Marijuana abuse and employment, an underrated problem].

PMID- 19107031
TI  - [Screening and treatment of marijuana abuse].

PMID- 19107032
TI  - [Integrating smoking intervention with patients].

PMID- 19107033
TI  - [Cognitive behavior therapy in smoking cessation].

PMID- 19107034
TI  - [Underrated effects of tobacco and marijuana smoking on the thyroid, the
      esophagus, the kidney, the skeletal system and the mouth].

PMID- 19107035
TI  - [Drug treatment for smoking and marijuana abuse].

PMID- 19107036
TI  - [Withdrawal for tobacco and marijuana smokers: when and how should the
      pulmonologist refer to an addiction specialist?].

PMID- 19107038
TI  - [Vitreous hemorrhage and whole-body vibration training--is there an
      association?].
AB  - Whole-body vibration training, i.e., standing in different static positions or
      exercising on a vibrating platform, has been promoted as an attractive and
      efficient complement, or even alternative, to resistance training. No ocular side
      effects have been described until now. We describe the case of a 43-year-old man
      who presented 2 weeks after starting whole-body vibration training with a
      spontaneous vitreous hemorrhage. We briefly discuss the ocular effects of
      habitual exposure to vibration described in the literature. This case suggests
      that whole body vibration training can cause spontaneous vitreous hemorrhage. To
      our knowledge, this is the first report of a possible ocular side effect of whole
      body vibration training.

PMID- 19107039
TI  - [Brain hypoperfusion revealed by an ocular ischemic syndrome].
AB  - We report the case of a 59-year-old female presenting an ocular ischemic syndrome
      caused by occlusion of the internal carotid artery. MRI showed multiple previous
      episodes of stroke. Therapy consisted in stopping the antihypertensive medication
      in order to stabilize the residual cerebral perfusion pressure and initiating
      statin and antiaggregant therapy.

PMID- 19107040
TI  - [Dynamic phototherapy as a treatment for central serous chorioretinopathy].
AB  - PURPOSE: To analyze the angiographic and tomographic results and the visual
      acuity of a group of patients presenting acute or chronic serous central
      chorioretinopathy (CSCR) treated with dynamic phototherapy. This treatment was
      guided by ICG angiography data. PATIENTS AND METHOD: We conducted a
      retrospective/prospective nonrandomized study on 31 eyes of 27 patients,
      including eight acute forms and 23 chronic forms. One or more spots were treated
      according to the age-related macular degeneration standard protocol on the zones
      of choroidal hyperpermeability highlighted by ICG angiography. The criteria for
      success were based on functional signs, visual acuity, persistence of a point of
      leakage in angiofluorographic follow-up at 3 months, and the OCT study of serous
      retinal detachment. RESULTS: An increase in visual acuity (3.58+/-3.22 lines,
      p<0.0001) was observed for all forms of treated CSCR; 90.32% patients presented a
      reapplication of serous retinal detachment within a period of 7.28+/-3.93 weeks.
      No retinal pigmentary epithelium tear or choroidal neovascularization was
      observed. Recurrence occurred in 12.9% patients within a period of 28+/-16.24
      weeks; only chronic CSCR cases were concerned. At 8+/-4.2 months, the visual
      acuity of the patients who had no recurrence remained unchanged (0.356+/-0.4
      LogMAR or 20/50-20/40). CONCLUSION: Although the number of patients included in
      this study is limited, dynamic phototherapy currently seems to be an effective
      and sure treatment of CRSC. A randomized study on a large series is necessary to
      confirm these results.

PMID- 19107041
TI  - [Traumatic wound dehiscence after keratoplasty].
AB  - PURPOSE: To assess the patient characteristics, risk factors, and outcomes of
      penetrating keratoplasty wound dehiscence. PATIENTS AND METHOD: Retrospective
      chart review of 11 eyes of 11 patients with corneal grafts who underwent repair
      of penetrating keratoplasty wound dehiscence from January 1986 to January 2006 in
      the Ophthalmology Department at the Besancon Minjoz Hospital (France). RESULT:
      The mean time between penetrating keratoplasty and wound dehiscence was 3.3 years
      (range, 1-140 months). In all cases, dehiscence involved the junction between
      graft and host. The mean age at time of wound dehiscence was 47 years (range, 23
      89 years). Falls were the most common mechanism of trauma, especially in the
      elderly population. There was a wide range of visual outcomes in the 11 patients,
      with six patients with best corrected visual acuity less than 1/20. There were no
      cases of endophthalmitis. CONCLUSION: Patients with corneal transplants have a
      life-long risk for wound traumatic dehiscence. This complication may be reduced
      by the regular use of eye protection by all corneal transplantation patients.

PMID- 19107042
TI  - [A study of refractive errors in a primary school in Cotonou, Benin].
AB  - PURPOSE: Determine the epidemiologic aspects and the degree of severity of
      different refractive errors in primary schoolchildren. PATIENTS AND METHODS: A
      prospective and descriptive study was conducted from 1 December 2005 to 31 March
      2006 on schoolchildren ranging from 4 to 16 years of age in a public primary
      school in Cotonou, Benin. The refraction was evaluated for any visual acuity
      lower than or equal to 0.7. RESULTS: The study included 1057 schoolchildren. The
      average age of the study population was 8.5+/-2.6 years with a slight
      predominance of females (51.8%). The prevalence of refractive error was 10.6% and
      astigmatism accounted for the most frequent refractive anomaly (91.9%). Myopia
      and the hyperopia were associated with astigmatism in 29.4% and 16.1% of the
      cases, respectively. The age bracket from 6 to 11 years accounted for the
      majority of refractive errors (75.9%), without age and sex being risk factors
      (p=0.811 and p=0.321, respectively). The average vision of the ametropic eye was
      0.61, with a clear predominance of slight refractive errors (89.3%) and
      particularly of low-level simple astigmatism (45.5%). CONCLUSION: The relatively
      low prevalence of refractive error observed does not obviate the need for
      implementing actions to improve the ocular health of schoolchildren.

PMID- 19107043
TI  - [Active drainage combined with air-fluid exchange for silicone oil removal:
      advantages and long-term follow-up].
AB  - INTRODUCTION: A number of silicone oil removal procedures are in use today. The
      purpose of this study was to evaluate the advantages of active drainage with air
      fluid exchange for silicone oil removal. PATIENTS AND METHODS: We conducted a
      prospective study on patients operated on for retinal detachment with vitrectomy
      with silicone oil intraocular tamponade between January 2005 and January 2006.
      The surgical procedures were three-port vitrectomy with silicone tamponade.
      Silicone oil was removed with active drainage and air-fluid exchanges. Visual
      acuity, floaters, intraocular pressure, emulsion, and silicone oil complications
      were evaluated at 3, 6, 12, and 18 months. RESULTS: Fifty patients (50 eyes)
      underwent vitrectomy with silicone oil intraocular tamponade for RD with
      proliferative vitreoretinopathy. The mean duration of intraocular silicone oil
      tamponade was 4.5 months (1-15 months). Seventeen patients had complementary
      procedures such as phacoemulsification, epimacular membrane peeling,
      complementary retinopexy or intravitreal triamcinolone. At 1 year, the mean
      visual acuity was 3.2/10. One patient reported floaters. One patient had
      recurrent retinal detachment, one patient had intraocular hypertony, and
      significant emulsion was found in one patient. Microscopic emulsion was found in
      20 patients. DISCUSSION: This surgical technique is longer and more invasive than
      simple passive ablation. However, complementary procedures could decrease the
      risk of recurrent retinal detachment and provide better visual rehabilitation.
      Better silicone oil removal seems to limit residual emulsion. CONCLUSION: Active
      drainage with air-fluid exchange for silicone oil removal is an interesting
      procedure. It could reduce short- and medium-term silicone oil complications in
      vitreoretinal surgery and increase the final visual outcome. However, a
      prospective comparative and randomized study is necessary to confirm our results.

PMID- 19107044
TI  - [Peribulbar anesthesia: efficacy of a single injection with a limited local
      anesthetic volume].
AB  - INTRODUCTION: Cataract surgery can be performed with peribulbar anesthesia. The
      classical technique consists of two injections of local anesthetics. The purpose
      of our study was to assess peribulbar anesthesia with a single injection and a
      limited volume of local anesthetics. MATERIAL AND METHOD: After local ethics
      committee agreement and oral consent, patients scheduled for cataract surgery
      using peribulbar anesthesia were prospectively included. The lower temporal
      puncture was performed with a peribulbar needle with propofol sedation. The
      mixture of local anesthetics was administered with tactile control of orbital
      pressure. The puncture was followed by a 10-min compression of the ocular globe.
      Akinesia, analgesia, complications, and surgical conditions were noted. RESULTS:
      A total of 101 successive patients were included. We administered 1.2 mg/kg of
      propofol. The volume of local anesthetics administered was 5.0 +/- 0.9 ml. Ninety
      patients had akinesia at 10 min and 6.7% moderate chemosis. No puncture
      complication occurred. At the end of surgery, the pain noted by the patients was
      0.4 +/- 2.1 out of 100 (range, 0-10). Surgical conditions were good for all
      patients. CONCLUSION: Peribulbar anesthesia performed with a single injection and
      a limited volume of local anesthetics allows cataract surgery in good conditions
      for the surgeon with very good analgesia for the patient.

PMID- 19107045
TI  - [Factors associated with graft reepithelialization after penetrating
      keratoplasty].
AB  - INTRODUCTION: To study graft reepithelialization time after penetrating
      keratoplasty and the factors influencing this reepithelialization. PATIENTS AND
      METHODS: In this retrospective study, 48 patients underwent penetrating
      keratoplasty (52 eyes) by the same surgeon between 1998 and 2006. Recipient pre-
      and postoperative variables, donor characteristics, and surgical variables were
      analyzed. Postoperative slit-lamp examination after fluorescein staining and
      graft reepithelialization time were recorded. Statistical analysis was done using
      SPSS version 11.5 (p<0.05). RESULTS: The average graft reepithelialization time
      was 8.02 +/- 6.87 days. Complete corneal epithelial healing was obtained in 2.2%,
      38.3%, and 63% of patients in 1, 3, and 7 days, respectively. There was a
      statistical correlation between graft reepithelialization time and trephination
      size, death-to-storage time, and storage time (p<0.05). DISCUSSION: Postoperative
      epithelial defects are common after penetrating keratoplasty. Many factors
      influence this graft reepithelialization such as abnormal lid and surface
      dysfunction, recipient corneal epithelium, and surgical technique. A better
      understanding of these factors will prevent postoperative epithelial defects and
      complications.

PMID- 19107046
TI  - [Current medical and surgical treatment of acute postoperative endophthalmitis].

PMID- 19107047
TI  - [Fluoroquinolones in ophthalmology: mechanisms of action and resistance].
AB  - The arrival of fluoroquinolones in the 1980s aroused enormous enthusiasm in the
      medical community, justified by the spectrum of antibacterial activity, good
      tolerance, and wide distribution in tissues, even after oral administration.
      However, the extensive use of these new antibiotiques finally ended in emerging
      resistance, which limits the efficiency of all the molecules in the class,
      including those that have appeared in the last few years. Ocular diseases also
      benefited from the emergence of fluoroquinolones, notably for topical treatments.
      It is now mandatory to adapt the prescriptions to the best indications, in order
      to protect the vast therapeutic potential of these molecules.

PMID- 19107048
TI  - [Fluoroquinolones in ophthalmology: indications and current use].
AB  - Fluoroquinolones are commonly used in ophthalmology, either for conjunctival
      infections or endophthalmitis. Use of these antibiotics requires good knowledge
      of the pharmacokinetic profile and adverse effects, and contraindications must be
      respected. Fluoroquinolones are useful in 2008 given their antibacterial
      spectrum, good ocular penetration, and the potential benefit of intravitreal
      injection.

PMID- 19107049
TI  - [Vitrectomy and endophthalmitis].
AB  - The decision to perform a vitrectomy in a case of endophthalmitis is mainly based
      on the Endophthalmitis Vitrectomy Study (EVS) conclusions. An emergency
      vitrectomy is helpful when the baseline visual acuity is lower than hand motion
      perceptions. However, various coexisting conditions should be considered: clear
      media and the availability of an operating room dedicated to emergency surgery.
      These limitations lead to a frequent delay in vitrectomy to assess the
      progression of the initial presentation after treatment with antibiotics and anti
      inflammatory agents. However, in these cases, the vitrectomy will remain
      restricted to the center of the vitreous cavity to limit peripheral retinovitreal
      traction favoring retinal detachment. Vitrectomy performed to treat the residual
      vitreous opacity or macular complications such as epiretinal membranes, subject
      to even greater delay, is another indication.

PMID- 19107050
TI  - [Intravitreal injection of antibiotics in endophthalmitis].
AB  - Early diagnosis and appropriate treatment with intravitreous antibiotics are the
      most important factors for the successful management of endophthalmitis. The
      intraocular concentration of antibiotics after intravitreous injection is far
      greater than that achieved by any other modality. The organisms in postoperative
      endophthalmitis are usually Gram-positive cocci and less commonly Gram-negative
      bacteria. Drug combinations are necessary to cover the full range of bacteria
      causing endophthalmitis. Vancomycin (1 mg/0.1 ml) is considered the drug of
      choice for Gram-positive organisms. Controversy remains concerning the best
      choice against Gram-negative bacteria. Aminoglycosides (amikacin, 0.4 mg/0.1 ml)
      have traditionally been recommended for Gram-negative coverage. However, because
      of their possible role in macular toxicity, recent trends have shifted to using
      ceftazidime (2.25 mg/0.1 ml) in combination with vancomycin.

PMID- 19107051
TI  - [Advantages of corticosteroids in managing acute bacterial postoperative
      endophthalmitis].
AB  - Most studies show a trend toward a beneficial or at least neutral effect of
      associating corticosteroids and antibiotics. However, caution must be taken, with
      various factors considered: the type, virulence, and size of the inoculum, and
      the treatment chosen. Early intravitreal administration of 400 microg of
      dexamethasone seems to be beneficial in treating postoperative Staphylococcus
      epidermidis-related endophthalmitis. However, a large-scale prospective,
      randomized, controlled study is mandatory to gain evidence supporting steroid
      therapy in postoperative endophthalmitis.

PMID- 19107053
TI  - Uveal effusion induced by topical travoprost in a patient with Sturge-Weber
      Krabbe syndrome.
AB  - PURPOSE: To report a case of uveal effusion with subtotal exudative retinal
      detachment induced by topical administration of travoprost. CASE REPORT: A 20
      year-old woman with a medical history of right-sided Sturge-Weber-Krabbe syndrome
      and bilateral aphakia secondary to congenital cataract extraction was referred to
      our department for retinal detachment associated with uveal effusion of the right
      eye. The ocular manifestations of Sturge-Weber-Krabbe syndrome in her right eye
      were glaucoma and diffuse choroidal hemangioma. Antiglaucomatous medications
      using topical travoprost 0.004%/timolol 0.5% (fixed combination) had been begun 1
      week before. An adverse effect of travoprost was suspected and the drug was
      discontinued. Three weeks later, a fundus examination showed total disappearance
      of the uveal effusion. CONCLUSIONS: Interaction of the effects of topical
      prostaglandin analogs (blood-aqueous barrier disruption, enhancement of
      uveoscleral outflow) with both the diffuse choroidal hemangioma and the elevated
      episcleral venous pressure may lead to uveal effusion in Sturge-Weber-Krabbe
      syndrome. In spite of their efficiency, prostaglandin F2 analogs (latanoprost,
      travoprost and bimatoprost) should be used with caution in Sturge-Weber-Krabbe
      syndrome and particularly in cases of proved diffuse choroidal hemangioma.

PMID- 19107055
TI  - [Contact lens fitting after keratoplasty for keratoconus].
AB  - PURPOSE: The objective of this study was to determine the epidemiological and
      clinical characteristics of contact lens fitting after corneal graft for
      keratoconus. Contact lens types, visual acuity and complications were examined.
      METHODS: A retrospective medical chart review from patients admitted to Pellegrin
      Hospital at CHU Bordeaux, between January 2001 and December 2006, for contact
      lens fitting after keratoplasty for keratoconus. RESULTS: This retrospective
      study involved 39 eyes of 29 patients with an average age of 34.3 years and an
      average follow-up of 31.3 months. The mean time between grafting and contact lens
      fitting was 50.9 months. Large-diameter rigid gas permeable contact lenses were
      the most frequent lenses used. Average visual acuity after contact lens fitting
      was 8/10. Intolerance to contact lenses was observed in 8 eyes (20.5%) eyes and
      the complications associated with their use responded well to medical treatment.
      CONCLUSION: Patients with keratoconus must be alerted to the possible necessity
      of fitting contact lenses after corneal graft. They can play an important role in
      the improvement of visual function without significant complications.

PMID- 19107054
TI  - [Optical coherence tomography: a reliable tool for localisation of macular
      hemorrhage. Two case reports].
AB  - Recent observations have found that premacular hemorrhage in Valsalva retinopathy
      is located under the internal limiting membrane. We confirm these findings in two
      case reports of Valsalva retinopathy. Visual acuity rehabilitation was obtained
      in the first case by conservative treatment and by draining the hemorrhage into
      the vitreous with Neodymium (Nd):Yag laser in the second case. We report the
      current therapeutic guidelines for Valsalva retinopathy, including the systematic
      search of autosomal dominant syndrome of retinal arterial tortuosity, a rare
      condition, often discovered after this type of benign macular hemorrhage.

PMID- 19107056
TI  - [Anterior segment analysis using OCT3].
AB  - PURPOSE: Optical coherence tomography has been used for many years, in particular
      in the field of the retinal imaging, and is a promising technique in the analysis
      of the anterior segment, providing a similar resolution to histology for ocular
      tissue. MATERIAL AND METHODS: We present a collection of images obtained with the
      OCT3 (Carl Zeiss Meditec, Dublin, CA), with parameters set to obtain good-quality
      images of the iris and corneal structures. RESULTS: The OCT provides detailed
      analysis of the cornea, precise assessment of the dimensions and locations of
      corneal lesions - in the anterior-posterior plane as well as transversally or
      obliquely - with 10-microm precision, and the study of the iridocorneal angle and
      its dynamics. DISCUSSION: Using the highly precise OCT3 for retinal imaging, it
      is possible to obtain good-quality anterior segment imaging, which makes the
      device highly versatile and thus increases reasons for acquiring this type of
      apparatus. CONCLUSIONS: OCT3 users should not neglect this potential of the
      device, already in wide use for examining the retina.

PMID- 19107057
TI  - [Improving medical information for patients with a customized website].
AB  - INTRODUCTION: In order to improve medical information for the patients consulting
      at the Department of Ophthalmology, an Internet website was set up. We wanted to
      estimate the rate of patients connecting to this website. Then we evaluated how
      the patients could draw a benefit from visiting this Internet site. PATIENTS AND
      METHODS: Prospective study of the patients seen in the department of
      ophthalmology over 4 consecutive days in May 2007. The first questionnaire was
      distributed to all patients and completed in the department. The second one was
      given only to the patients equipped with a broadband Internet connection and was
      to be completed at home after having visited the website. RESULTS: Six hundred
      twenty-one patients were admitted to the department during the period; 510 (82%)
      were included in the study. Among them, 382 (74.9%) responded to the first
      questionnaire. The broadband connection rate was 42.5%, 74.5% of these patients
      took an interest in our site, and 64.6% thought of visiting it. Forty-two (29%)
      responded to the second questionnaire. After having visited the site, 61.2% of
      the patients felt that their medical information was improved, 71.8% rated the
      quality of the site as good, and 87.9% would recommend this site to their
      relatives. CONCLUSION: This type of website is liable to efficiently supplement
      the information provided by the Ophthalmology Department doctors. It justifies
      the time and staff investment necessary for its operation.

PMID- 19107058
TI  - [Vitreoretinal outpatient surgery: clinical and financial considerations].
AB  - INTRODUCTION: Vitreoretinal surgery has benefited from great advances opening the
      opportunity for outpatient management. METHODS: We report on the 6-month
      experience of outpatient surgery for vitreoretinal diseases. RESULTS: From
      November 2007 to April 2008, 270 patients benefited from a vitreoretinal surgery,
      with 173 retinal detachments, 63 epiretinal membranes, and 34 other procedures.
      Only 8.5% (n=23) of the patients had to stay at the hospital one or two nights.
      The main reasons were the distance from the hospital and surgery on a single-eye
      patient. The questionnaire given after the surgery showed that almost all the
      patients were satisfied with the outpatient setting. In contrast, the financial
      results showed a loss of income of around 400,000 euros due to the low level of
      payment of outpatient surgery in France by the national health insurance system.
      DISCUSSION: Vitreoretinal surgery can be achieved in outpatient surgery with an
      improvement in the information given to the patients and the overall organization
      of the hospitalization. However, the current income provided with vitreoretinal
      outpatient surgery is highly disadvantageous in France, preventing this method
      from being generalized.

PMID- 19107059
TI  - [Choroidal metastasis from clinically regressed prostate adenocarcinoma: imaging
      of a rare case].
AB  - INTRODUCTION: Choroidal metastases are often the revealing feature of malignant
      diseases. We report a rare case of prostatic adenocarcinoma metastases at the
      choroids, diagnosed and followed by fluorescein angiography (FA), indocyanine
      green angiography (ICGA), and optical coherence tomography (OCT-3 Stratus).
      OBSERVATION: A 54-year-old man was referred to our department for decreased
      vision in his left eye lasting for 1 month. On ophthalmic evaluation, best
      corrected visual acuity (BCVA) was 20/20 in his right eye and 20/63 in his left
      eye. Biomicroscopic examination of the anterior segments did not reveal anything
      abnormal in either eye. Funduscopic examination revealed two amelanotic choroidal
      masses in both his right and left eyes, located at the posterior pole and at the
      periphery. The systemic workup, including hematologic analysis and total-body
      computed tomography (CT), revealed elevated serum prostate-specific antigen (PSA)
      and alkaline phosphatase, extensive abnormalities of the axial skeleton, and
      nodular pulmonary shadows; therefore, prostatic adenocarcinoma was suspected.
      Needle biopsies (prostatic and pulmonary) confirmed adenocarcinoma of the
      prostate, with metastatic disease. We decided to submit the patient to
      intermittent total androgen blockade alone, without adjunctive radiotherapy. The
      patient responded well to intermittent total androgen blockade with oral
      bicalutamide and triptorelin injection alone, as documented on fundus pictures,
      ultrasonography, OCT, FA, and ICGA. DISCUSSION: Prostatic carcinoma should be
      considered in any male patient with a choroidal mass suspected of being a
      metastasis. In our patient, FA, ICGA, and OCT clearly documented the complete
      regression of choroidal metastasis from prostatic carcinoma. Fluorescein
      angiography, indocyanine-green angiography, and optical coherence tomography are
      useful tools in the diagnosis and follow-up of prostatic adenocarcinoma
      metastatic to the choroid.

PMID- 19107060
TI  - [Lacquer cracks complicated with choroidal neovascularization in pseudoxanthoma
      elasticum: the first case report in Burkina Faso].
AB  - Lacquer cracks are breaks in the Bruch membrane by alteration of the elastic
      layer. They are often associated with pseudoxanthoma elasticum. The authors
      report the first case in Burkina Faso involving a 51-year-old woman who was seen
      for visual acuity loss. She had pseudoxanthoma elasticum associated with lacquer
      cracks complicated by choroidal neovascularization in both eyes. She was treated
      with laser photocoagulation of the neovessels in the left eye, and no recurrence
      was reported after 6 months.

PMID- 19107061
TI  - [Foreword: new corneal grafts].

PMID- 19107062
TI  - [Will penetrating keratoplasty become obsolete?].
AB  - The development of technologies for performing lamellar cuts of the cornea
      constitutes a major breakthrough in corneal grafting, since it can bypass the
      well-identified limits of penetrative keratoplasty such as intraocular pressure
      elevation and graft rejection with nonreversible edema, which are major but
      unpredictable complications of penetrative keratoplasty. A surgical procedure
      that could exchange only pathologic tissue layers might be able to eliminate all
      these adverse events and provide faster visual recovery with better visual
      performance. However, certain indications for penetrative graft will certainly
      remain, benefiting from the considerable progress in surgical technique with the
      advent of femtosecond laser and the the control of immunomodulation. This article
      develops arguments to answer the three following questions: Why should we replace
      penetrative keratoplasty? Why will this procedure survive? How can we improve it?

PMID- 19107063
TI  - [Deep lamellar anterior keratoplasty].
AB  - Penetrating keratoplasty is the most common method of corneal graft no matter
      which pathology is present. The surgical procedure is easy but unnecessary
      substitution of healthy recipient endothelium in diseases affecting only the
      anterior layers exposes the patient to the risk of immunologic rejection.
      Lamellar keratoplasty was the first procedure described. It has become less
      popular because it is technically difficult to perform and often has poor visual
      results due to imperfect lamellar dissection. Recent advances in surgical
      techniques enable us to manage these difficulties and lamellar keratoplasty may
      well become the first choice of treatment for most stromal diseases.

PMID- 19107064
TI  - [Endothelial keratoplasty].
AB  - In recent years, endothelial keratoplasty has become increasingly popular in the
      management of endothelial pathologies of the cornea. This technique is primarily
      indicated in pseudophakic keratopathy and Fuchs dystrophy and significantly
      reduces known complications that occur after penetrating keratoplasty (i.e.,
      major astigmatism, graft junction weakness, ocular surface diseases). Visual
      recovery is also more rapid. The endothelium is removed using a reverse hook or
      forceps and replaced by an endothelial graft that also includes a certain stromal
      thickness. The preparation of the donor graft can be automated by using a
      microkeratome or can be performed manually on artificial anterior chamber.
      Although automated dissection techniques have become the most popular approach,
      thin posterior graft can only be obtained using a manual dissection procedure.
      Several studies are currently underway to assess the possibility of reducing
      endothelial cell injury when preparing and inserting the graft. Progress in this
      specific field of research will greatly encourage future use of endothelial
      keratoplasty.

PMID- 19107065
TI  - [Femtosecond laser-assisted keratoplasties].
AB  - Femtosecond laser technology in ophthalmology is not only used for refractive
      surgery (LASIK flaps), but also now for lamellar and penetrating keratoplasties.
      This is not surprising when one knows that femtosecond lasers can cut corneal
      tissue in all directions with micrometric accuracy. Lamellar dissection of the
      cornea is very facilitated with femtosecond laser because it is quicker and more
      reproducible. However, predescemet dissection is not yet possible, and although
      the interfaces are smooth, the visual benefits of this technology has still to be
      proven. Another field of application of femtosecond lasers is their use to
      perform the cut for penetrating keratoplasties. Different shapes of non vertical
      cuts are currently assessed in order to reduce the incidence of complications
      such as induced astigmatism and wound dehiscence, and to improve the visual
      outcome.

PMID- 19107066
TI  - [Eyelid necrosis caused by an hymenopteran insect bite].
AB  - We report a case report of extensive eyelid necrosis caused by an insect bite. A
      39-year-old man had suffered ocular trauma from a hymenopteran insect in Tunisia.
      The patient presented with eyelid necrosis. Eyelid necrosis mechanisms following
      insect bites are discussed and other causes of eyelid necrosis are presented.
      Eyelid necrosis, often caused by vasoconstrictive medications or animal venoms,
      notably hymenopteran insect bites, can result in substantial eyelid injury.

PMID- 19107068
TI  - [Chronic central serous chorioretinopathy and photodynamic therapy: a case
      report].
AB  - Chronic central serous chorioretinopathy (CCSC) with recurrent and prolonged
      exudative retinal detachment may cause multiple degenerative manifestations with
      poor visual acuity. By acting on choroidal hyperpermeability, photodynamic
      therapy seems to be a useful treatment for symptomatic CCSC. We present the case
      of a 60-year-old patient presenting with symptomatic CCSC complicated with serous
      retinal detachment lasting more than 1 year. Visual acuity on the left eye was
      1/20. Photodynamic therapy with indocyanine green angiography guidance was
      provided. Subretinal fluid was rapidly resolved and visual acuity improved to
      7/10. Photodynamic therapy influences choroidal hyperpermeability and thus
      resolves serous retinal detachment in CCSC. Visual acuity improvement
      particularly depends on preexisting macular atrophy.

PMID- 19107070
TI  - [Evaluation of the Ocular Response Analyzer in ocular hypertension, glaucoma, and
      normal populations. Prospective study on 329 eyes].
AB  - OBJECTIVES: (1) Evaluate and analyze the Ocular Response Analyzer (ORA) in three
      groups of patients: glaucoma, intraocular hypertension, and normal; (2) study
      corneal hysteresis values in the three groups according to age; and (3) compare
      intraocular pressure values measured with the ORA with intraocular pressure
      measured with Goldmann (IOPGoldmann) and pulsed air (IOPair) applanations.
      MATERIAL AND METHODS: This prospective, single-center study included 329 eyes
      divided into three groups: normal (n=207), intraocular hypertension (n=55), and
      primary angle glaucoma (n=67). Corneal hysteresis (CH), IOP corneal-compensated
      (IOPcc), and Goldmann correlated IOP (IOPg) measurements were provided by the ORA
      device for all patients. Ultrasonic central corneal thickness (CCT US), and
      intraocular pressure measured with Goldmann and pulsed air tonometry were also
      assessed in each eye. RESULTS: The mean values were: IOPGoldmann 14.4+/-3.4 mmHg,
      IOPair 15.5+/-3.6 mmHg, CCT 542.1+/-36.6 microm, CH 10+/-1.7 mmHg, IOPcc 16.6+/
      4.1 mmHg, and IOPg 15.7+/-3.9 mmHg. All the IOP measurements (IOPGoldmann,
      IOPair, IOPg, IOPcc) were strongly correlated into the three age groups. The mean
      CH in the glaucoma (9.8 mmHg) and intraocular hypertension (9.6 mmHg) groups was
      lower than in the normal group (10.3 mmHg), but there was no difference between
      the three groups for the CH values, with an age-related analysis of the three
      groups. The CH was correlated with CCT US in the three groups. IOP measures were
      not strongly correlated with CH except for IOPcc. There was a negative
      correlation (-0.79) between CH and IOPcc. DISCUSSION/CONCLUSION: In our study,
      the mean ORA, CCT US, and IOP values in the normal group were similar to those
      found in the literature. These are the first CH values reported for a normal
      group according to age. We confirm the good correlation between all the IOP
      measurements. The mean corneal hysteresis value was low in glaucoma and
      intraocular hypertension, but there was no difference between the three groups
      for the CH values, when the three groups were analyzed according to age. There
      was a correlation between corneal hysteresis and central corneal thickness.
      Moreover, IOPcc seems to be the best evaluation of IOP with no influence from
      corneal biomechanical factors. The Ocular Response Analyzer and corneal
      hysteresis should be considered a useful parameter for patients with intraocular
      hypertension and/or glaucoma.

PMID- 19107071
TI  - [Intra-annual and seasonal allergic conjunctivitis treatment: comparison of two
      therapeutic protocols].
AB  - INTRODUCTION: Allergic conjunctivitis is the most common form of conjunctivitis
      encountered in daily ophthalmological practice. Its therapy can be problematic:
      it must be simple, free of complications, and adaptable to everyday life.
      PATIENTS AND METHODS: We conducted a randomized prospective single-center survey
      on 102 patients between 4 and 80 years of age who presented moderate allergic
      conjunctivitis. Patients were divided into two groups, one treated in monotherapy
      with N-acetyl-aspartyl glutamic acid (NAAGA) over 4 weeks and the other treated
      with bi-therapy (NAAGA and Levocabastine during the first week and NAAGA only for
      the next 3 weeks), with evaluation of the sum of the scores of the cardinal signs
      of allergic conjunctivitis at D0, D7 and D28. RESULTS: The two populations were
      homogeneous at inclusion: the majority of the patients had a history of
      allergies, with a nonspecific disrupted allergy workup (IgE and eosinophils) and
      a higher initial score for the children included in the study. The scores
      decreased sharply at D7 (50% reduction) and at D28 (bordering 1) with no
      significant difference between the two groups. Tolerance to the treatment judged
      by unusual sensations upon instillation was better for the NAAGA treatment (80.8%
      of the cases). Clinical and functional signs disappeared without recourse to
      corticoids. CONCLUSION: In the moderate forms of seasonal and intra-annual
      allergic conjunctivitis, NAAGA treatment alone is sufficient. The association
      with Levocabastine is necessary only in cases of highly bothersome functional
      signs. The use of corticoids should be reserved for the serious forms.

PMID- 19107072
TI  - [Corneal tattooing. A series of 14 case studies].
AB  - AIMS: Evaluate the efficacy of a little-used surgical method: corneal tattooing,
      using a dermograph to hide unsightly corneal scars on nonfunctional eyes.
      PATIENTS AND METHODS: Retrospective study of 14 eyes of 13 patients treated by
      tattooing the corneal surface, by directly introducing the pigments into the
      corneal stroma using a dermograph. The effectiveness of tattooing was evaluated
      by pigmentation homogeneity and patient satisfaction. Tolerance was evaluated by
      the scarring at the 7th day and ocular inflammation. The average follow-up was 18
      months. RESULTS: Fourteen eyes presented an unaesthetic, neovascularized major
      corneal edema (79% traumatism). In 12 eyes, the treatment was homogeneous with a
      very satisfactory aesthetic result for the patient. One eye presented minor
      complications of pigmentary migration. One eye presented a corneal perforation 40
      days after the procedure on a very pathological cornea. CONCLUSION: Corneal
      tattooing using a dermograph is a little-used technique since changes in corneal
      transplantation indications but is also a simple and inexpensive alternative for
      corneal scar treatment on nonfunctional eyes.

PMID- 19107073
TI  - [Oxidative stress modulation using polyphenol-rich blueberries: application on a
      human retinal cell model].
AB  - INTRODUCTION: The retina is located in a highly oxygenated environment and is
      therefore particularly susceptible to oxidative damage. Blueberries have a high
      antioxidant potential since they are rich in anthocyans. The aim of this study
      was to investigate the cytoprotective role of blueberries on human retinal cells.
      MATERIALS AND METHODS: Blueberry extract was incubated at 0.05% and 0.1% for 15
      minutes or 24 hours on a human retinal cell line. Then oxidative stress was
      induced by 150 microM tert-butylhydroperoxide (tBHP) for 1 hour. Intracellular
      metabolism, reactive oxygen species, superoxide anion, and mitochondrial
      apoptosis were evaluated using Alamar blue, DCFDA, dihydroethidium, and
      nonylacridine orange dyes, respectively. Tests were performed using
      cytofluorometry adapted to microplates. RESULTS: Blueberry protected cells
      against tBHP-induced cytotoxicity. It increased cell viability, decreased
      oxidative stress and mitochondrial apoptosis. After a 24-hour preincubation time,
      blueberry totally inhibited tBHP-induced cytotoxicity. CONCLUSION: Blueberry
      seems to be a potent antioxidant and could be easily added to food complements to
      prevent or limit ocular pathologies induced by oxidative stress.

PMID- 19107074
TI  - [Two-year outcomes of selective laser trabeculoplasty in open-angle glaucoma and
      ocular hypertension].
AB  - BACKGROUND: Selective laser trabeculoplasty (SLT) is a relatively new treatment
      strategy for the treatment of glaucoma. Its principle is similar to that of argon
      laser trabeculoplasty (ALT), but may lead to less damage to the trabecular
      meshwork. METHODS: We assessed the 2-year efficacy of SLT in a noncomparative
      consecutive case series. Any adult patient either suspected of having glaucoma or
      with open-angle glaucoma, whose treatment was judged insufficient to reach target
      intraocular pressure (IOP), could be recruited. IOP and number of glaucoma
      treatments were recorded over 2 years after the procedure. RESULTS: Our sample
      consisted of 44 consecutive eyes of 26 patients, aged 69+/-8 years. Eyes were
      treated initially on the lower 180 degrees . Three of them were retreated after
      15 days on the upper 180. Fourteen eyes had ocular hypertension, 17 primary open
      angle/normal-tension glaucoma, 11 pseudoexfoliation (PEX) glaucoma, and two
      pigmentary glaucoma. Thirty-six eyes had previously been treated and continued to
      be treated with topical anti-glaucoma medication, ten had had prior ALT, nine
      iridotomy, and 12 filtering surgery. The 2-year-follow up could not be completed
      for eight eyes because they needed filtering surgery. In the remaining 36 eyes,
      IOP decreased by a mean of 17.2%, 3.3 mmHg, (19.2+/-4.7 to 15+/-3.6 mmHg) after 2
      years (p<0.001). As a secondary outcome, the number of glaucoma treatments
      decreased from 1.44 to 1.36 drops/patient. Other results according to subgroups
      of patients are analyzed: the greatest IOP decrease occurred in eyes that had
      never been treated with anti-glaucoma medication or with PEX glaucoma. SLT was
      probably valuable in a few eyes after filtering surgery; however, the statistical
      power of the study was not strong enough to draw a firm conclusion. When
      expressed in survival curves after 2 years, however, only 48% and 41% of eyes
      experienced a decrease of more than 3 mmHg or more than 20% of preoperative
      intraocular pressure, respectively. CONCLUSION: SLT decreases IOP somewhat for at
      least 2 years without an increase in topical glaucoma treatment. However, it
      cannot totally replace topical glaucoma treatment. In the future, patient
      selection should be improved to decrease the cost/effectiveness ratio.

PMID- 19107075
TI  - [Screening for sickle cell disease retinopathy in the north of France].
AB  - OBJECTIVE: To study the frequency and the severity of retinopathy in adult
      patients with sickle cell disease in the north of France. PATIENTS AND METHODS:
      Patients with sickle cell disease aged more than 18 years old were consecutively
      referred for screening of sickle cell retinopathy in the ophthalmology department
      from December 2005 to March 2008. Complete ophthalmologic examination with
      dilated funduscopy was performed in each patient. Fluorescein angiography was
      performed in cases with ischemic retinopathy. Goldberg and Penman classifications
      were used to grade retinopathy severity. RESULTS: Fifty-five patients (100 eyes)
      were included (26 S/S, 9 S/C, 12 S/B, 3 S/S with hereditary persistence of fetal
      hemoglobin). Sickle cell retinopathy is more severe in patients with the S/C
      genotype than the S/S and S/B genotypes. Proliferative retinopathy is more common
      in S/C patients than S/S and S/B patients (S/C vs S/S, p=0.001; S/C vs SB,
      p=0.01). A qualitatively abnormal vascular border (type II) is also more frequent
      in S/C patients than S/S and S/B patients (S/C vs S/S, p=0.001; S/C vs SB,
      p=0.01). No proliferative retinopathy was found in patients with S/S and
      hereditary persistence of fetal hemoglobin syndrome. CONCLUSIONS: Screening is
      useful to detect sickle cell retinopathy, particularly in the adult population,
      to prevent complications from proliferative retinopathy.

PMID- 19107076
TI  - [Long-chain 3-hydroxyacyl CoA dehydrogenase deficiency and choroidal
      neovascularization].
AB  - We report the case of a 9-year-old girl with a long-chain 3-hydroxyacyl CoA
      dehydrogenase (LCHAD) deficiency. This enzyme participates in mitochondrial fatty
      acid B-oxidation. Genetic fatty acid oxidation defects induce cellular energetic
      deficiency, and thus early life-threatening manifestations. An appropriate diet
      prevents these severe disorders. Nevertheless, LCHAD deficiency is the only B
      oxidation enzymatic disorder that induces a chorioretinopathy, predominating at
      the posterior pole. We describe the first case of bilateral macular choroidal
      neovascularization. One eye presented a fibrovascular lesion. The other eye
      presented an active neovascularization stabilized by two dynamic phototherapies.
      The specificity of choroidal degeneration related to LCHAD deficiency remains
      unknown. Reviewing of literature and biochemical mechanisms suggests that fatty
      acid oxidative stress rather than a mitochondrial energetic defect is involved.
      For practical purposes, this report emphasizes the importance of ophthalmological
      follow-up of these patients.

PMID- 19107077
TI  - [Correlation between corneal hysteresis, corneal resistance factor, and ocular
      pulse amplitude in healthy subjects].
AB  - PURPOSE: The Ocular Response Analyzer (ORA) measures corneal biomechanical
      properties: corneal hysteresis (CH) and the corneal resistance factor (CRF). The
      Pascal Dynamic Contour Tonometer (PDCT) measures the ocular pulse amplitude
      (OPA), which represents the systolic-diastolic variation in intraocular pressure
      (IOP). Both ORA and OPA values are lower in glaucoma patients than in normal
      patients. Our purpose was to assess whether there is a correlation between CH,
      CRF, and OPA values in healthy subjects. DESIGN AND PARTICIPANTS: Prospective
      observational study including 81 eyes of 41 healthy adult volunteers. Patients
      with ocular eye disease, previous refractive or intraocular surgery, contact
      lenses, or topical or general medications were excluded. METHODS: Patients
      underwent four ORA, three OPA, and two Goldmann Applanation Tonometry (GAT)
      measurements. For each device, the mean of all measurements were considered for
      this study. The statistical analysis by Spearman rank correlations was performed
      for right (RE), left (LE), and both eyes. The correlation between the two eyes of
      each subject was taken into account and canonical correlations were calculated
      using the SAS statistical software to improve the power of the analysis. RESULTS:
      The mean age was 43.6 +/- 14.6 years. The mean central corneal thickness was 545
      +/- 32 microm for RE, 553 +/- 34 microm for LE, and 550 +/- 32 microm for both
      eyes. The mean IOPGAT values for RE, LE, and both eyes were, respectively 14.3 +/
      2.9 mmHg, 14.0 +/- 2.9 mmHg, and 14.2 +/- 2.9 mmHg. Spearman correlations were
      not statistically significant for separated RE and LE analysis. For both eyes,
      these correlations were rS=0.210, p=0.193 for OPA/CH and rS=0.388, p=0.013 for
      OPA/CRF. The Spearman correlation was statistically significant for OPA/CRF. This
      result was confirmed by canonical correlations (p=0.002) and in addition, CH was
      statistically correlated to OPA in the latter analysis (p=0.010). CONCLUSION: A
      statistically significant correlation was found between corneal biomechanical
      property values as measured by ORA and ocular pulse amplitude values as measured
      by PDCT in healthy subjects.

PMID- 19107078
TI  - [Surgical treatment of diffuse adult orbital lymphangioma: two case studies].
AB  - PURPOSE: Orbital lymphangioma is a rare vascular malformation; it is a benign but
      severe anomaly because of its infiltrative, diffuse, and hemorrhagic nature, and
      its high morbidity rate. Surgical resection is a real challenge on account of the
      intricate architecture of the lesion. The authors report their surgical
      experience concerning two cases of diffuse orbital lymphangioma whose diagnosis
      was established in adulthood and whose surgical treatment was successful. CASE
      REPORTS: Two patients presented with adult orbital lymphangioma. Progression was
      slow during the first decade and then was quickly followed by complications:
      major exorbitism, compressive optic neuropathy, and corneal exposure.
      Neuroimaging showed a diffuse and cystic orbital malformation. Surgical resection
      was performed as completely as possible, in one case with a Kronlein orbitotomy
      and in the other case only via a conjunctive route. An aspirate drain was put in
      the orbit for 48 h so as to prevent dead spaces forming after resection, an
      essential risk factor of hemorrhagic or cystic recurrence. Systemic
      corticotherapy was administered for the 5 days following surgery. The resection
      was total in one case and subtotal in the other. The surgical follow-up was
      uneventful with an excellent aesthetic result and an improvement in visual
      acuity. After 12 months, no tumoral or hemorrhagic recurrence was noted.
      DISCUSSION: The surgical treatment of orbital lymphangiomas is challenging
      because of their infiltrative nature. In diffuse forms, a complete resection is
      rarely possible because of the risk of sacrificing visual function. In the two
      cases reported herein, the resection of the extraconal portion was complete, but
      the intraconal portion was completely removed only in one case. Using the
      aspirate drain, negative pressure was maintained in the orbital cavity,
      preventing the formation of chocolate cysts induced by surgery. Although the
      clinical result was very satisfying, long-term follow-up is necessary to evaluate
      recurrence. CONCLUSION: Diffuse orbital lymphangiomas can be treated successfully
      with a subtotal resection without clinical recurrence in the short term. These
      results are promising because they demonstrate that many orbital lymphangiomas
      can benefit from surgical treatment with an excellent esthetic and functional
      result.

PMID- 19107079
TI  - [Central serous chorioretinopathy: a study of six cases observed in Abidjan
      between 2003 and 2005, suggesting a role played by the Ivorian political-military
      crisis].
AB  - OBJECTIVE: This study aimed to show that central serous chorioretinopathy is
      present in Ivory Coast and that the emotional and psychosocial context plays an
      important role in this disorder's pathogenesis. PATIENTS AND METHOD: The authors
      report six central serous chorioretinopathy cases based on angiographic
      diagnosis, five in Black African subjects and one in a European subject. These
      cases were observed over a period of 2 years during the Ivorian political
      military crisis. RESULTS: In a center where angiography has been a current
      practice since 1999, up to 2002 479 angiographies were done without a single
      central serous chorioretinopathy case being diagnosed. After the beginning of the
      political-military crisis, six cases of central serous chorioretinopathy were
      observed out of 417 angiographies over a period of 2 years. All the patients were
      males, between 20 and 50 years old, five were Black Africans and one was a white
      European. Their professions varied (a contractor, a soldier, a business
      executive, for example). The angiography showed break points in ink spots in the
      majority of the cases, with one case showing multiple break points. All the
      patients were emotionally distraught because of the uncertainty of the political
      situation. CONCLUSION: This study confirms that central serous chorioretinopathy
      does indeed exist in the Black African subject, as it exists in the leucoderma
      subject without discrimination. This study emphasizes the anxiety and extreme
      emotional context as an initiating factor in the occurrence of central serous
      chorioretinopathy.

PMID- 19107081
TI  - [Adenomatous hyperplasia of the conjunctiva].
AB  - We report a case of adenomatous hyperplasia of the conjunctiva. A 42-year-old man
      was referred for a left conjunctival lesion involving the caruncle; the
      histopathological patterns revealed benign adenomatous hyperplasia, a disease
      that may originate in the conjunctiva. Adenomatous hyperplasia of the conjunctiva
      is a benign condition. The absence of cytonuclear anomalies and mitotic activity
      distinguishes adenomatous hyperplasia from adenocarcinoma and mucoepidermoid
      carcinoma.

PMID- 19107080
TI  - [Systemic tolerance of corticosteroid therapy in ophthalmology depending on the
      route of administration].
AB  - Corticosteroids have been a major therapeutic improvement, particularly in
      ophthalmology. Depending on the different therapeutic modalities used, the
      ophthalmologist will mainly encounter a risk of short-term adverse effects
      (intravenous administration, high doses, etc.) or a risk of long-term side
      effects (related to the cumulative dose received). In any case, the underlying
      status of each patient must be carefully assessed in order to choose the best
      individual treatment modalities that will minimize the risk of undesirable
      effects. Intravitreal and topical steroid administrations do not seem to be
      associated with a significant risk of systemic adverse effects, because blood
      diffusion of the product is minimal. Conversely, periocular injections lead to a
      rapid and nearly total systemic diffusion of the steroid, with hyperglycemic
      effects similar to those observed after intravenous pulse methylprednisolone.
      Thus, periocular and intravenous routes of administration carry similar risks of
      systemic effects and both cases require similar monitoring, with strict blood
      glucose monitoring useful in diabetic patients only. The various systemic
      complications of long-term oral steroid therapy can be reduced by always
      prescribing the minimal efficient dosage for controlling the disease, together
      with preventive measures against adverse effects when possible, e.g., the
      prevention of corticosteroid-induced osteoporosis. In the future, new
      glucocorticoids or agonists, e.g., the dissociated glucocorticoids or SEGRAs
      (SElective Glucocorticoid-Receptor Agonists), now in clinical development, should
      further reduce the risk of adverse effects of steroids while maintaining their
      remarkable anti-inflammatory action.

PMID- 19107083
TI  - [Sjogren's Syndrome and its unrevealed secrets].

PMID- 19107084
TI  - [Nailfold capillaroscopy in children and adolescents with rheumatic diseases].
AB  - Nailfold capillaroscopy is a simple, noninvasive and inexpensive method which
      allows a functional and morphological study of the capillary network through
      direct visualization of the distal row of periungueal capillaries of the fingers.
      This method has been used as a diagnostic auxiliary in diseases such as
      scleroderma, dermatomyositis, systemic lupus erythematosus and mixed connective
      tissue disease. It has also been used to differentiate between active and non
      active diseases, especially dermatomyositis, and to distinguish between primary
      and secondary Raynaud's phenomenon. Most reports of nailfold capillaroscopy are
      qualitative and semi-quantitative. Manuscripts describing quantitative methods
      (video-capillaroscopy) are scarce, particularly in childhood. The authors did a
      literature review based on Medline, Lilacs and Pubmed data using the keywords:
      nailfold capillaroscopy, colagenosis, Raynaud, children and adolescents.

PMID- 19107085
TI  - The clinical importance of lymphadenopathy in systemic lupus erythematosus.
AB  - Lymphadenopathy (LAP) is a frequent and usually nonspecific feature of Systemic
      Lupus Erythematosus (SLE). In spite of the fact that LAP usually carries no risk
      to the patient, SLE patients with LAP were found to have higher disease activity
      levels. Besides the disease itself, other causes of LAP such as infections,
      immunological or malignant diseases must be considered in the differential
      diagnosis. LAP is a prominent clinical characteristic of Kikuchi-Fujimoto's
      disease which is associated with fever, arthralgia, and leukopenia, features also
      found in SLE. As the prognosis and treatment of KFD and SLE are different, it is
      important to differentiate these two entities. On the other hand, the increased
      risk of lymphoproliferative diseases in SLE was reported in several studies.
      Since there is a considerable overlap between the features of SLE and lymphoma,
      there can be a difficulty in diagnosing lymphoma in lupus patients. An increased
      awareness is recommended in dealing with SLE patients with LAP and careful
      clinical, laboratory and pathological evaluation are often needed in order to
      establish an accurate diagnosis.

PMID- 19107086
TI  - Screening of family members of children with Familial Mediterranean Fever: true
      autosomal and pseudo-autosomal inheritance.
AB  - OBJECTIVES: Screening of family members of children with Familial Mediterranean
      Fever (FMF) has been carried out to detect new potential patients and to analyze
      the type of inheritance other than autosomal recessive. METHODS: Marenostrin
      encoding fever gene mutational analysis has been performed in 83 subjects -
      including 19 newly diagnosed children with FMF and their family members. RESULTS:
      Fourteen additional patients with FMF were diagnosed by screening family members.
      Pseudo-dominant and true dominant inheritances were detected in two families
      respectively, while the rest of the patients exhibited autosomal recessive mode
      of inheritance. CONCLUSION: Screening the family members of newly diagnosed FMF
      patients provides the opportunity to reveal undiagnosed new cases and to
      understand the mode of inheritance.

PMID- 19107087
TI  - [Salivary gland scintigraphy in the evaluation of patients with sicca
      complaints].
AB  - Salivary gland scintigraphy is a non invasive method widely accepted as an
      objective assessment of salivary gland function and a diagnostic criterion of
      primary Sjogren's Syndrome. In this study we evaluated the performance of
      qualitative and semi--qualitative salivary gland scintigraphy in primary
      Sjogren's Syndrome. Additionally we aimed to identify the scintigraphic patterns
      of salivary gland involvement in this condition. PATIENTS AND METHODS:
      Observational study of fifty--six women with suspected primary Sjogren's Syndrome
      (pSS). Investigation included clinical history and observation, ophtalmologic
      examination, autoantibodies (SSA and SSB) determination, minor salivary gland
      biopsy and salivary gland scintigraphy interpreted according to Schall
      classification, visual quality of radioactivity uptake, morphology of time
      activity curves and semi-quantitative parameters of uptake and excretion.
      RESULTS: Twenty patients fulfilled diagnostic criteria for pSS. Submandibular
      glands showed more pronounced functional impairment. In pSS patients, all
      scintigraphic parameters were significantly lower on these glands: a) qualitative
      evaluation ' visual quality of uptake (p=0,003), morphology of time-activity
      curves (p=0,001) and Schall classification (p<0,001); b) semi-quantitative
      parameters ' maximum counts (p=0,005), maximum counts/second/MBq administered
      (p=0,01), index of maximum counts versus counts at first minute (p=0,002) and
      excretion index (p=0,006). CONCLUSIONS: Despite being qualitative and observer
      dependent, Schall classification is valuable for the diagnosis of primary
      Sjogren's Syndrome. Nevertheless, semi-quantitative evaluation of salivary gland
      scintigraphy reveals significant differences in pSS patients and may have
      incremental value for the interpretation of salivary gland scintigraphy results.

PMID- 19107088
TI  - [Non-steroidal anti-inflammatory drugs prescription in General Practice setting:
      435 does informatics have any influence?].
AB  - AIMS: In the ambulatory setting of General Practice/Family Medicine, a
      retrospective, observational study was carried out to ascertain variation on non
      steroidal anti-inflammatory drugs prescription, in an informatics environment
      where name (brand or chemical), size of package, price and the existence of
      generic medicines is available. METHODS: Observational transversal study
      conducted in February 2008 with no prescription study warning given to the
      doctors in the study period. The differences in volume prescription in Daily
      Defined Dose (DDD) per registered patient in the middle of 2006 and 2007 two
      semesters, as well as the value of prescription measured by the price per
      registered patient were calculated and medicines were studied by the third level
      of the Portuguese medicines classification very similar to the ATC. The price per
      DDD was calculated as well. RESULTS: DDD volume and value declined throughout the
      study comparing entire years or semesters being "Oxicans" the only exception.
      Even though, the net volume and value decreased between 2006 and 2007 comparing
      both semesters of 2006 and of 2007. Price per DDD decreased for all medicines
      except for oxicans with an increase from the first to the second semesters of
      2007. CONCLUSIONS: Informatics environment influences the prescription of non
      steroidal anti-inflammatory drugs, reducing the number of DDD and the price per
      registered patient.

PMID- 19107089
TI  - [Back school for patients with non-specific chronic low-back pain: benefits from
      the association of an exercise program with patient's education].
AB  - OBJECTIVE: <<Back School>> has been used as a way of preventing and treating back
      pain since 1969, but reports in the literature on its effectiveness remain
      controversial. The purpose of this trial was to evaluate efficacy of a back
      school program for non- -specific chronic low-back pain. PATIENTS AND METHODS:
      Seventy patients were randomized into two groups: experimental group (34
      patients) and control group (36 patients). Experimental group patients
      participated in a theoretical and practical back school program, which was
      composed of 4 weekly classes of 60 minutes. Control group patients were allocated
      at a waiting list. Three evaluations took place (baseline, after 4 and 16 weeks).
      The following variables were analyzed: pain intensity (visual numeric analogue
      scale), functional disability (Roland-Morris Disability Questionnaire) and spinal
      mobility (Schober index). Statistical analysis for intra-group and inter-group
      used significance level of p < 0.05. RESULTS: 57 patients were analyzed (29 in
      experimental group and 28 in control group). A statistically significant
      improvement was observed only in the experimental group, regarding pain
      intensity, functional disability and spine mobility. Such improvements have
      persisted after 16 weeks in pain intensity and functional disability variables.
      In the inter-group analysis we observed a statistically significant difference in
      the second and third evaluations concerning the functional disability variables
      and spinal mobility. CONCLUSION: The Back School program proposed in this study
      seems to be effective for non-specific chronic low back pain.

PMID- 19107090
TI  - [Hemorrhagic vesicle-bullous lesions in Henoch-Schonlein purpura and review of
      literature].
AB  - INTRODUCTION: The characteristic feature of Henoch-Schonlein purpura (HSP) is
      palpable purpura, however hemorrhagic vesicles and blisters have been rarely
      reported. CASE REPORTS: From January 1983 to December 2007, 5079 patients were
      followed in our Pediatric Rheumatology Unit, 232 (4.6%) of them with the
      diagnosis of HSP. Three female patients (1.3%) presented hemorrhagic vesicles and
      bullous lesions associated with palpable purpura. In one case the lesions were
      severe and widespread, and in another they preceded the typical purpuric lesions.
      In both cases, skin biopsy disclosed leukocytoclastic vasculitis with IgA and C3
      deposits. Two patients healed with residual lesions: ulcers in one case and skin
      hyperpigmentation in two of them. DISCUSSION: Hemorrhagic vesicle-bullous lesions
      are rare in HSP. This manifestation may represent a more severe and prolonged
      disease course with scars or may precede typical skin lesions.

PMID- 19107091
TI  - [Lymphoedema in systemic juvenile arthritis: a rare extraarticular feature].
AB  - Extraarticular features are usually found in rheumatological diseases sometimes
      with no correlation with the disease's activity in that moment. Lymphoedema is
      one of these manifestations and it's defined as a tissue fluid accumulation with
      gradual onset of swelling of a limb. Because it is an unusual finding, the
      physiopatological explanation of this feature is still difficult to understand.
      We describe a case report of lymphoedema on left upper arm, in a patient with
      systemic juvenile arthritis, with no identified cause and with no associated
      systemic signs or symptoms.

PMID- 19107092
TI  - [Multiple enchondromatosis: Ollier's disease].

PMID- 19107093
TI  - [Structural lesion and disability - not only rheumatoid arthritis but also
      osteoarthritis].

PMID- 19107094
TI  - Fibromyalgia in between: where do the musculoskeletal physicians and
      psychiatrists stand?

PMID- 19107095
TI  - Drugs for hypertension.

PMID- 19107096
TI  - Advances in colonoscope technique and technology.
AB  - To date, no alternative platform for colonoscopy seems prepared to substantially
      supplant the traditional colonoscopy platform. The Invendoscope and capsule
      colonoscopy are the most promising of the alternative platforms. With regard to
      colonoscope insertion, water immersion is quite noteworthy but requires
      additional study in broader populations. The benefits of cap-fitted colonoscopy
      for insertion are small. With regard to imaging, wide-angle colonoscopy may
      produce an operator-dependent improvement in efficiency, but there is no
      consistent evidence that it improves adenoma detection. Similarly, cap-fitted
      colonoscopy is not convincing as a method to improve adenoma detection. There is
      no method for seeing flat lesions that is both effective and practical for high
      level white light adenoma detectors. Narrow-band imaging may have a learning
      effect on low-level adenoma detectors, and autofluorescence seems promising and
      deserves additional study. Several methods for determination of real-time
      histology are promising and seem to be methods by which the cost-effectiveness of
      colonoscopy could be improved through reduction in pathology charges for
      diminutive polyps.

PMID- 19107097
TI  - Gastroesophageal reflux disease and obesity.
AB  - Although the balance of epidemiologic data supports a relationship between
      obesity and gastroesophageal reflux disease (GERD), it is difficult to establish
      true cause and effect. However, results of several studies show that the
      frequency and severity of GERD symptoms and complications may be higher in obese
      patients, including an increase in the presence of hiatal hernia. Additionally,
      findings of a recent meta-analysis demonstrate a statistically significant
      increase in the risk for GERD symptoms, erosive esophagitis, and esophageal
      adenocarcinoma in obese patients. No definitive study is available, however, to
      suggest deviating from standard GERD screening or treatment guidelines for the
      obese patient. Physicians should approach obese patients with GERD as they do
      those with reflux disease and ideal body weight. The recommendation of weight
      loss for the obese patient with GERD is reasonable to improve GERD physiology and
      symptoms. Lifestyle modifications and medical therapy with a proton pump
      inhibitor (PPI) once daily before breakfast for 4 to 8 weeks should be initiated.
      Antireflux surgery is always an option for patients with GERD who have a
      symptomatic response to PPIs. Prospective studies directed at the obese patient
      are needed to determine if different approaches are required.

PMID- 19107098
TI  - Certolizumab pegol: a polyethylene glycolated Fab' fragment of humanized anti
      tumor necrosis factor alpha monoclonal antibody for the treatment of Crohn's
      disease.
AB  - Certolizumab pegol offers an alternative to the other biologic response modifiers
      for the treatment of Crohn's disease. Results from phase II dose-ranging studies
      were mixed because a number of the studies had high placebo response rates and a
      large number of patients with low C-reactive protein (CRP) levels. Phase III
      clinical trials have demonstrated induction of clinical responses and maintenance
      of remission for patients independent of whether baseline CRP levels were normal
      or elevated. Although concomitant immune suppressants reduced the immunogenicity,
      there were no differences in clinical response at 6 to 12 months for patients
      receiving immunosuppressives compared with those not receiving concomitant
      medications. There is also evidence that patients treated earlier in the course
      of disease may have improved responses and that patients who have lost response
      to infliximab will respond to certolizumab pegol.

PMID- 19107100
TI  - Infectious disease. Vancomycin should be the drug of choice for severe
      Clostridium difficile-associated diarrhea.

PMID- 19107101
TI  - Mucosal healing in inflammatory bowel disease.

PMID- 19107102
TI  - Diagnosis and management of esophageal disease.

PMID- 19107103
TI  - Can nutritional therapy replace pharmacologic therapy in pediatric Crohn's
      disease?

PMID- 19107104
TI  - Liver transplantation for sclerosing cholangitis in a polytraumatized patient.
AB  - BACKGROUND: Following a motorcycle accident, a 30-year-old male with multiple
      traumas-including liver rupture, traumatic fractures, cerebral hemorrhage,
      hepatic hematoma and respiratory failure-was referred to a university medical
      center. After initial stabilization, the patient developed pneumonia, acute
      kidney failure requiring intermittent hemodialysis, superinfection of the hepatic
      hematoma and systemic bacterial infection with multiple drug-resistant bacteria.
      The patient developed acute liver failure 8 weeks after the initial trauma.
      INVESTIGATIONS: Laboratory investigations, Doppler ultrasound, CT, ultrasound,
      angiography, endoscopic retrograde cholangiography, liver biopsy, bacteriology
      and X-ray. DIAGNOSIS: Sclerosing cholangitis in a critically ill patient.
      MANAGEMENT: Orthotopic liver transplantation.

PMID- 19107105
TI  - Why do patients on peritoneal dialysis have low blood levels of protein-bound
      solutes?

PMID- 19107107
TI  - Treatment of infantile spasms in tuberous sclerosis complex: dismal outcomes but
      future hope?
AB  - This commentary discusses a retrospective study by Muzykewicz et al. that details
      EEG results from children with infantile spasms in the setting of tuberous
      sclerosis complex (TSC). In this study, several factors were identified as being
      predictive of poor cognitive outcome, including worsening degree of
      hypsarrhythmia, abnormalities in EEG background activity, and incomplete response
      to vigabatrin. Notably, the majority of patients had a poor outcome, experiencing
      cognitive impairment and intractable epilepsy irrespective of whether they were
      treated with adrenocorticotropic hormone (corticotropin) or vigabatrin, despite
      the fact that vigabatrin has shown promise in previous studies. However, among
      the entire cohort a third of patients enjoyed greater than 1 year of seizure
      freedom and about a quarter had either mild or no cognitive impairment at follow
      up. Overall, these findings underscore the great challenges that are faced in the
      treatment of infantile spasms in patients with TSC. I suggest that, while
      vigabatrin has been shown to have impressive short-term efficacy, the intractable
      seizures and cognitive impairment in many patients with TSC strongly indicate
      that new therapies and treatment strategies are urgently needed.

PMID- 19107106
TI  - The role of obesity in the pathogenesis of hypertension.
AB  - The rapid rise in the incidence and prevalence of obesity and the concomitant
      increase in the incidence and prevalence of hypertension have fueled
      investigation into the role of obesity in the pathogenesis of hypertension. The
      genetic background that predisposes obese individuals to hypertension is being
      elucidated, and the importance of adipose tissue as an endocrine organ in the
      pathogenesis of hypertension is increasingly being recognized. Visceral adipose
      tissue is critical in the production of pathologic cytokines that are thought to
      mediate obesity-induced hypertension. Changes in the types and levels of
      adipocytokines that result from the accumulation of aberrant adipose tissue
      directly leads to alterations in systemic vascular resistance, sodium retention
      and sympathetic nervous system activity. Key changes in adipocytokine levels seen
      in obesity-induced hypertension include increased leptin and adiponectin levels.
      Another important mechanism in obesity-induced hypertension is the generation of
      angiotensin II and direct stimulation of aldosterone production. The increased
      sympathetic nervous system activity seen in obesity-associated hypertension leads
      to increased renal sodium retention and increased systemic vascular resistance.
      Increased systemic vascular resistance can also occur directly in obese
      individuals through vascular fibrosis and lipid deposition. Obesity should no
      longer be simply considered as a marker of cardiovascular risk but should be
      regarded as an important and primary contributor to the pathophysiology of
      hypertension.

PMID- 19107108
TI  - Thrombolysis with alteplase for acute ischemic stroke: safe and effective outside
      the 3-hour time window?
AB  - This Practice Point commentary discusses an observational study by Wahlgren et
      al. that examined the use of intravenous alteplase in a routine clinical setting
      3-4.5 h after onset of stroke. The study recruited patients from the SITS-ISTR
      thrombolysis registry. The outcomes of 664 patients treated with intravenous
      alteplase at between 3 h and 4.5 h after stroke onset were compared with those of
      11,865 patients treated within 3 h. No significant differences were noted between
      the two cohorts at 3 months regarding the rate of symptomatic intracerebral
      hemorrhage, mortality, or functional independence. The study provides invaluable
      information about the safety of alteplase for acute stroke when used within this
      extended time frame, although the investigation lacked comprehensive central
      auditing of the data, and it was difficult to ascertain whether all patients
      treated in the participating centers were included in the dataset and to verify
      that no biased reporting occurred.

PMID- 19107109
TI  - Trastuzumab as adjuvant systemic therapy for HER2-positive breast cancer.
AB  - Trastuzumab has an established role for the treatment of HER2-positive early
      stage breast cancer because of the success of this agent in the adjuvant setting.
      Several key questions about the value of trastuzumab for the treatment of breast
      cancer, however, still need to be answered. Various differences in patient
      characteristics and treatment regimens were present in the randomized trials
      discussed in this Review; therefore, the details of trastuzumab use need
      clarification. For example, the optimum timing, the ideal administration
      schedule, and the appropriate length of treatment are not known. Cardiotoxicity
      is major concern even though the results of all randomized trials have shown that
      the degree of cardiotoxicity with trastuzumab is acceptable -- the incidence of
      cardiac damage caused by trastuzumab ranged from 0.4% to 4.1% in the different
      trials (cumulative incidence of congestive heart failure, New York Heart
      Association class 3-4). Current data do not support the use of trastuzumab for
      more than 1 year. The analysis of 2-year treatment with trastuzumab is expected
      to be available in 2009.

PMID- 19107111
TI  - Deficiencies in current evaluations of the cost-effectiveness of biologic agents
      for RA.

PMID- 19107110
TI  - Melanoma biomarkers: current status and vision for the future.
AB  - Melanoma is the leading cause of death from skin cancer in industrialized
      countries. Clinical and histological variables such as primary tumor invasion,
      ulceration, and lymph node status might fail to identify early-stage disease that
      will eventually progress. Tumor biomarkers might help to identify patients with
      early-stage melanoma who are likely to develop advanced disease and would benefit
      from additional therapies. These biomarkers offer the possibility of improved
      tumor staging through the molecular detection of microscopic lymph node
      metastases that are not visible on routine histological examination. We focus on
      biomarkers localized to the tumor tissue and those of prognostic value. We give
      an overview of the melanoma biomarkers that are most helpful for prediction of
      patients' outcomes, and discuss the primary melanoma biomarkers that have been
      shown to be of prognostic significance independent of primary tumor thickness and
      other common clinical prognostic indicators. Although such tumor-associated
      biomarkers are thought to have the greatest potential, a lack of reliable data
      makes their true clinical utility difficult to determine. We conclude that
      several biomarkers show promise in early studies; however, additional large-scale
      studies are warranted. We suggest cautious optimism for the field of melanoma
      biomarkers, which we expect to be translated into clinical practice over the next
      few years.

PMID- 19107112
TI  - RADIATE: more treatment options for patients with an inadequate response to tumor
      necrosis factor antagonists.
AB  - Over the last decade, the use of tumor necrosis factor (TNF) inhibitors has
      improved the prognosis of patients with rheumatoid arthritis. Although these
      agents are more efficacious than traditional DMARDs, a substantial proportion of
      patients discontinue anti-TNF therapy because of adverse effects or lack of
      efficacy. Therapeutic options for these patients include dose increases,
      switching to an alternative TNF antagonist, or switching to a biologic of a
      different class, such as rituximab or abatacept. The recently published results
      of the RADIATE study by Emery et al. suggest that the interleukin-6 inhibitor
      tocilizumab is a safe and effective alternative for patients who fail to respond
      to anti-TNF therapy. Randomized controlled trials and the study of biomarkers are
      needed to help clinicians select the most suitable of these options for their
      patients.

PMID- 19107113
TI  - Should an antimuscarinic agent be used for persistent LUTS after treatment with
      an alpha(1)-blocker?
AB  - This Practice Point discusses the study by MacDiarmid and colleagues, which is
      the latest to support a beneficial effect of adding antimuscarinic agents to
      alpha(1)-blockers in men with persistent lower urinary tract symptoms. Such
      studies have also alleviated concerns about the adverse effects of antimuscarinic
      agents, particularly the risk of developing urinary retention. In practice,
      however, some issues regarding the use of antimuscarinic agents in this patient
      population remain. First, persistent storage symptoms are suggestive of other
      pathologies, and this possibility must be carefully evaluated before combined
      treatment is initiated. Second, postvoid residual urine volume should be
      repeatedly monitored during antimuscarinic therapy to avoid sequelae of residual
      urine or urinary retention. Third, the effect of adding an antimuscarinic agent
      is statistically significant, but might not be clinically significant for the
      majority of men. Better evaluation of storage symptoms might facilitate the more
      appropriate use of combined treatment in this setting.

PMID- 19107114
TI  - High complication rates challenge the implementation of male circumcision for HIV
      prevention in Africa.
AB  - This commentary discusses the study by Bailey and colleagues, who aimed to assess
      the safety of male circumcision practices in both clinical and traditional
      settings in Bungoma, Kenya. The study evaluated 1,007 males who underwent
      circumcision in a clinical (n = 562) and traditional (n = 445) setting. All young
      men who underwent circumcision were interviewed after surgery to assess their
      satisfaction and complication rates, and a sample of the practitioners who
      performed the circumcisions were interviewed to determine their circumcision
      training and experience. Additionally, 24 circumcision procedures (12 each in the
      clinical and traditional settings) were directly observed by the study
      investigators. The study found complications rates of 17.7% and 35.2% in the
      clinical and traditional groups, respectively. Furthermore, the study revealed
      shortcomings in practitioner knowledge, training and resources in both groups.
      Before scaling up male circumcision services in countries with a high prevalence
      of HIV, a careful strategy to minimize unnecessary morbidity, and fundamental
      improvements on current circumcision techniques, are required.

PMID- 19107115
TI  - Genome-wide association study of recurrent major depressive disorder in two
      European case-control cohorts.
AB  - Major depressive disorder (MDD) is a highly prevalent disorder with substantial
      heritability. Heritability has been shown to be substantial and higher in the
      variant of MDD characterized by recurrent episodes of depression. Genetic studies
      have thus far failed to identify clear and consistent evidence of genetic risk
      factors for MDD. We conducted a genome-wide association study (GWAS) in two
      independent datasets. The first GWAS was performed on 1022 recurrent MDD patients
      and 1000 controls genotyped on the Illumina 550 platform. The second was
      conducted on 492 recurrent MDD patients and 1052 controls selected from a
      population-based collection, genotyped on the Affymetrix 5.0 platform. Neither
      GWAS identified any SNP that achieved GWAS significance. We obtained imputed
      genotypes at the Illumina loci for the individuals genotyped on the Affymetrix
      platform, and performed a meta-analysis of the two GWASs for this common set of
      approximately half a million SNPs. The meta-analysis did not yield genome-wide
      significant results either. The results from our study suggest that SNPs with
      substantial odds ratio are unlikely to exist for MDD, at least in our datasets
      and among the relatively common SNPs genotyped or tagged by the half-million-loci
      arrays. Meta-analysis of larger datasets is warranted to identify SNPs with
      smaller effects or with rarer allele frequencies that contribute to the risk of
      MDD.

PMID- 19107116
TI  - RNA interference targeting STIM1 suppresses vascular smooth muscle cell
      proliferation and neointima formation in the rat.
AB  - Our objective was to study the expression and function of stromal interaction
      molecule 1 (STIM1), an endoplasmic reticulum protein recently identified as the
      calcium sensor that regulated Ca(2+)-released activated channels in T cells.
      STIM1 was found to be upregulated in serum-induced proliferating human coronary
      artery smooth muscle cells (hCASMCs) as well as in the neointima of injured rat
      carotid arteries. Growth factors-induced proliferation was significantly lower in
      hCASMC transfected with STIM1 siRNA than in those transfected with scrambled
      siRNA (increase relative to 0.1% S: 116 +/- 12% and 184 +/- 16%, respectively, P
      < 0.01). To assess the role of STIM1 in preventing vascular smooth muscle cells
      (VSMCs) proliferation in vivo, we infected balloon-injured rat carotid arteries
      with an adenoviral vector expressing a short hairpin (sh) RNA against rat STIM1
      mRNA (Ad-shSTIM1). Intima/media ratios reflecting the degree of restenosis were
      significantly lower in Ad-shSTIM1- infected arteries than in Ad-shLuciferase
      infected arteries (0.34 +/- 0.02 vs. 0.92 +/- 0.11, P < 0.006). Finally, we
      demonstrated that silencing STIM1 prevents activation of the transcription factor
      NFAT (nuclear factor of activated T cell). In conclusion, STIM1 appears as a
      major regulator of in vitro and in vivo VSMC proliferation, representing a novel
      and original pharmacological target for prominent vascular proliferative
      diseases.

PMID- 19107117
TI  - MicroRNAs and the regulation of vector tropism.
AB  - Despite being small (approximately 22 nt) microRNAs (miRNAs) profoundly influence
      tissue-specific gene expression by interacting with complementary target
      sequences in cellular messenger RNAs, impairing their translation or marking them
      for early destruction. Recent work has shown that tissue-specific miRNAs offer a
      versatile target that can be exploited to control the tropisms of gene expression
      vectors and of replication-competent viruses. The principle of incorporating
      miRNA targets into vector genomes to control their tropisms was first
      demonstrated for nonreplicating lentiviral and adenoviral vectors, with
      subsequent extension of these studies to replication-competent (oncolytic)
      picornaviruses, rhabdoviruses, and adenoviruses. In contrast to previous
      targeting approaches, miRNA targeting looks set to be applicable across the
      entire spectrum of viruses and gene expression vectors. Here we provide a
      critique of the literature relevant to this new and rapidly developing field of
      endeavor. We also examine the possibility of engineering viruses for expression
      of tropism-regulating miRNAs.

PMID- 19107119
TI  - Selective enhancement of the uptake and bioactivity of a TAT-conjugated peptide
      inhibitor of glycogen synthase kinase-3.
AB  - The use of cell-penetrating peptides as transduction vectors is a promising
      approach to deliver peptides and proteins into cells. However, the uptake and
      bioavailability of trans-activating transcriptor (TAT)-conjugated molecules vary
      depending on the cell type and the cargo. This study aimed to determine whether a
      low-voltage electrical pulse can enhance the TAT-mediated delivery of peptide
      cargoes in different cell types. In TF-1 and mouse embryonic stem cells, the
      uptake of a novel detachable TAT-conjugated glycogen synthase kinase-3 (GSK-3)
      peptide inhibitor was enhanced by an order of magnitude without affecting the
      cell viability. A similar increase in uptake was achieved in primary mouse bone
      marrow cells while maintaining >80% of their viability. Interestingly, under
      these low-voltage conditions, the uptake of a control peptide not conjugated to
      TAT was not significantly increased. A T-cell factor/lymphoid enhancer factor
      (TCF/LEF) luciferase reporter assay was also used to assess the bioactivity of
      the TAT construct. The results indicated that cells loaded with a low-voltage
      electrical pulse had a twofold increase in TCF/LEF activity, which was equivalent
      to a level of GSK-3 inhibition similar to that of cells treated with 20 mmol/l
      lithium or 500 nmol/l (2'Z,3'E)-6-bromoindirubin-3'-oxime. These results
      demonstrate the usefulness of low-voltage electrical pulses to enhance the uptake
      and bioactivity of TAT-conjugated molecules in different cell types.

PMID- 19107118
TI  - Acid ceramidase upregulation in prostate cancer cells confers resistance to
      radiation: AC inhibition, a potential radiosensitizer.
AB  - Radiation resistance in a subset of prostate tumors remains a challenge to
      prostate cancer radiotherapy. The current study on the effects of radiation on
      prostate cancer cells reveals that radiation programs an unpredicted resistance
      mechanism by upregulating acid ceramidase (AC). Irradiated cells demonstrated
      limited changes of ceramide levels while elevating levels of sphingosine and
      sphingosine-1-phosphate. By genetically downregulating AC with small interfering
      RNA (siRNA), we observed radiosensitization of cells using clonogenic and
      cytotoxicity assays. Conversely, AC overexpression further decreased sensitivity
      to radiation. We also observed that radiation-induced AC upregulation was
      sufficient to create cross-resistance to chemotherapy as demonstrated by
      decreased sensitivity to Taxol and C(6) ceramide compared to controls. Lower
      levels of caspase 3/7 activity were detected in cells pretreated with radiation,
      also indicating increased resistance. Finally, utilization of the small molecule
      AC inhibitor, LCL385, sensitized PPC-1 cells to radiation and significantly
      decreased tumor xenograft growth. These data suggest a new mechanism of cancer
      cell resistance to radiation, through upregulation of AC that is, in part,
      mediated by application of the therapy itself. An improved understanding of
      radiotherapy and the application of combination therapy achieved in this study
      offer new opportunities for the modulation of radiation effects in the treatment
      of cancer.

PMID- 19107120
TI  - Detection of intact rAAV particles up to 6 years after successful gene transfer
      in the retina of dogs and primates.
AB  - Gene transfer to the retina using recombinant adeno-associated viral (rAAV)
      vectors has proven to be an effective option for the treatment of retinal
      degenerative diseases in several animal models and has recently advanced into
      clinical trials in humans. To date, intracellular trafficking of AAV vectors and
      subsequent capsid degradation has been studied only in vitro, but the fate of AAV
      particles in transduced cells following subretinal injection has yet to be
      elucidated. Using electron microscopy and western blot, we analyzed retinas of
      one primate and four dogs that had been subretinally injected with AAV2/4, -2/5,
      or -2/2 serotypes and that displayed efficient gene transfer over several years.
      We show that intact AAV particles are still present in retinal cells, for up to 6
      years after successful gene transfer in these large animals. The persistence of
      intact vector particles in the target organ, several years postadministration, is
      totally unexpected and, therefore, represents a new and unanticipated safety
      issue to consider at a time when gene therapy clinical trials raise new
      immunological concerns.

PMID- 19107121
TI  - Extracellular superoxide dismutase is a growth regulatory mediator of tissue
      injury recovery.
AB  - Extracellular superoxide dismutase (SOD3) gene therapy has been shown to
      attenuate tissue damages and to improve the recovery of the tissue injuries, but
      the cellular events delivering the therapeutic response of the enzyme are not
      well defined. In the current work, we overexpressed SOD3 in rat hindlimb ischemia
      model to study the signal transduction and injury healing following the sod3 gene
      transfer. The data suggest a novel sod3 gene transfer-derived signal transduction
      cascade through Ras-Mek-Erk mitogenic pathway leading to activation of AP1 and
      CRE transcription factors, increased vascular endothelial growth factor (VEGF)-A
      and cyclin D1 expression, increased cell proliferation, and consequently improved
      metabolic functionality of the injured tissue. Increased cell proliferation could
      explain the improved metabolic performance and the healing of the tissue damages
      after the sod3 gene transfer. The present data is a novel description of the
      molecular mechanism of SOD3-mediated recovery of tissue injury and suggests a new
      physiological role for SOD3 as a Ras regulatory molecule in signal transduction.

PMID- 19107124
TI  - The role of thermogenesis in antipsychotic drug-induced weight gain.
AB  - The administration of antipsychotic drugs to human patients or experimental
      animals leads to significant weight gain, which is widely presumed to be driven
      by hyperphagia; however, the contribution from energy expenditure remains
      unclear. These studies aim to examine the contribution of shifts in energy
      expenditure, particularly those involving centrally mediated changes in
      thermogenesis, to the body weight gain associated with the administration of
      olanzapine to female Sprague Dawley rats. Olanzapine (6 mg/kg/day orally) caused
      a transient increase in food intake but a maintained increase in body weight.
      When pair-fed rats were treated with olanzapine, body weight continued to rise
      compared to vehicle-treated rats, consistent with a reduction in energy
      expenditure. Brown adipose tissue (BAT) temperature, measured using biotelemetry
      devices, decreased immediately after the onset of olanzapine treatment and
      remained depressed, as did physical activity. UCP1 expression in interscapular
      BAT was reduced following chronic olanzapine treatment. An acute injection of
      olanzapine was preceded by an injection of a retrograde tracer into the spinal
      cord to evaluate the nature of the olanzapine-activated neural pathway. Levels of
      Fos protein in a number of spinally projecting neurons within discrete
      hypothalamic and brainstem sites were elevated in olanzapine-treated rats. Some
      of these neurons in the perifornical region of the lateral hypothalamus (LHA)
      were also Orexin A positive. These data collectively show a significant impact of
      thermogenesis (and physical activity) on the weight gain associated with
      olanzapine treatment. The anatomical studies provide an insight into the central
      neuroanatomical substrate that may subserve the altered thermogenic responses
      brought about by olanzapine.

PMID- 19107122
TI  - Activation of Akt as a mechanism for tumor immune evasion.
AB  - Immune evasion is an important reason why the immune system cannot control tumor
      growth. To elucidate the mechanism for tumor immune evasion, we generated an
      immune-resistant human papillomavirus type 16 (HPV-16) E7-expressing tumor cell
      line by subjecting a susceptible tumor cell line to multiple rounds of in vivo
      immune selection with an E7-specific vaccine. Comparison of parental and immune
      resistant tumors revealed that Akt is highly activated in the immune-resistant
      tumors. Retroviral transfer of a constitutively active form of Akt into the
      parental tumor significantly increased its resistance against E7-specific CD8(+)
      T-cell mediated apoptosis. The observed resistance against apoptosis was found to
      be associated with the upregulation of antiapoptotic molecules. We also observed
      that intratumoral injection of an Akt inhibitor enhanced the therapeutic efficacy
      of E7-specific vaccine or E7-specific CD8(+) T-cell adoptive transfer against the
      immune-resistant tumors. Thus, our data indicate that the activation of PI3K/Akt
      pathway represents a new mechanism of immune escape and has important
      implications for the development of a novel strategy in cancer immunotherapy
      against immune-resistant tumor cells.

PMID- 19107125
TI  - Management of obesity: a challenge for medical training and practice.
AB  - Health-care providers are in a unique position to encourage people to make
      healthy lifestyle choices. However, lifestyle modification counseling is a
      complex task, made even more so by the cultural and socioeconomic diversity of
      patient populations. The objective of this study is to evaluate the prevalence
      and predictors of attending and physician-in-training weight control counseling
      in an urban academic internal medicine clinic serving a unique low-income
      multiethnic high-risk population. In 2006, patients (n = 256) from the Associates
      in Internal Medicine clinic (Division of General Medicine at the New York
      Presbyterian Hospital, Columbia University Medical Center, New York, NY) were
      recruited and completed a questionnaire, which assessed demographic variables,
      health conditions, access to health-care services, physician weight control
      counseling, and weight loss attempts. Seventy-nine percent of subjects were
      either overweight or obese. Only 65% of obese subjects were advised to lose
      weight. Attending physicians were more likely than physicians-in-training to
      counsel subjects on weight control (P < 0.01). Factors that were significantly (P
      < 0.05) associated with different types of weight control counseling included
      obesity, cardiovascular disease (CVD) risk factors, female gender, nonblack race,
      college education, married status, and attending physician. Subjects advised to
      lose weight were more likely to report an attempt to lose weight (P < 0.01).
      Rates of weight control counseling among physicians are suboptimal, particularly
      among physicians-in-training. Training programs need to promote effective
      clinical obesity prevention and treatment strategies that address socioeconomic,
      linguistic, and cultural factors.

PMID- 19107126
TI  - Regulation of pituitary gene expression by adrenalectomy.
AB  - Excessive secretion of adrenal hormones, such as glucocorticoid and
      mineralocorticoid, leads to metabolic syndrome, including insulin resistance,
      obesity, and hypertension. These metabolic abnormalities are ameliorated by
      adrenalectomy (ADX). To identify pituitary mediators for ADX-induced
      physiological alterations, such as weight loss and hypotension, we investigated
      the effect of ADX on the pituitary transcriptome using serial analysis of gene
      expression (SAGE). SAGE method is based on isolation of short sequence tags,
      which usually correspond to unique mRNA species. The SAGE libraries were
      constructed from pituitary gland of intact (n = 51) and ADX (n = 12) mice. Thirty
      one transcripts were differentially expressed between intact and ADX. Three
      transcripts encoding for proopiomelanocortin and three other transcripts involved
      in regulation of hormone secretion (neuromedin B, proprotein convertase
      subtilisin/kexin type 2, and IA-2) were induced by ADX. In addition, ADX
      increased the expression levels of genes encoding for cation extracellular matrix
      (matrix gamma-carboxyglutamate protein) and transport (solute carrier family 22
      member 17). Conversely, ADX downregulated two transcripts involved in
      mitochondrial oxidative phosphorylation (nicotinamide adenine dinucleotide (NADH)
      dehydrogenase 3 and cytochrome c oxidase 3). Moreover, ADX significantly
      modulated the expression levels of one gene with uncharacterized function and 20
      novel transcripts. This study reveals alterations of pituitary gene expressions
      that may be associated with ADX-induced physiological changes including weight
      loss.

PMID- 19107127
TI  - Overweight and obesity in young and middle age and early retirement: the ARIC
      study.
AB  - The objective of this study was to examine associations between weight status in
      young and middle age and early retirement in African-American and white men and
      women. Data were from the Atherosclerosis Risk in Communities (ARIC) study.
      Analyses were restricted to participants aged 45-55 years at baseline (n =
      6,483). Associations between weight status at age 25 and ages 45-55 and age at
      early retirement (prior to age 65) over 9 years of follow-up were examined using
      proportional hazard regression analyses in models stratified by race and gender.
      Models were adjusted for education, household income, health insurance status,
      occupation, occupational physical activity, marital status, smoking, and field
      center. Between 18.7 and 21.6% of African-American and white men and women
      reported retiring prior to age 65. Although not always statistically significant,
      overweight and obesity were associated with early retirement in all but white
      women. Overweight (BMI >or= 25 kg/m(2)) at age 25 was significantly associated
      with early retirement in African-American women (hazard ratio (95% confidence
      interval): 1.62 (1.17-2.23)) and white men (1.32 (1.12-1.57)). There was also a
      trend between overweight at age 25 and early retirement in African-American men
      (1.43 (0.99-2.07)). Obesity (BMI >or= 30 kg/m(2)) in middle age was significantly
      associated with early retirement in white men only (1.32 (1.03-1.69)).
      Furthermore, overweight at age 25 and obesity at ages 45-55 were associated with
      early retirement for health reasons among African-American and white men and
      women. In conclusion, analyses of the economic impact of obesity may need to
      consider its effects on early retirement.

PMID- 19107128
TI  - Influence of waist on adiponectin and insulin sensitivity in adolescence.
AB  - It has been hypothesized that abdominal obesity leads to insulin resistance
      partly through decreased adiponectin. However, the cross-sectional and
      longitudinal associations among waist, adiponectin, and insulin sensitivity have
      not been examined in older adolescents. Non-Hispanic white and black children
      were recruited from the Minneapolis school district and underwent three
      examinations at mean ages 13, 15, and 19. Insulin sensitivity (measured using the
      gold-standard euglycemic clamp) and waist circumference were measured at all
      exams. Adiponectin was measured at mean ages 15 and 19. Partial correlations were
      used to examine associations among waist, adiponectin, and insulin sensitivity at
      mean age 15 (n = 308) and mean age 19 (n = 218). Longitudinal correlations and a
      longitudinal regression model were used to predict adiponectin and insulin
      sensitivity measured at ages 15 and 19, from age 13 waist and change in waist. At
      age 15, waist and adiponectin were significantly correlated (r = -0.32). At age
      19, waist and adiponectin were significantly correlated (r = -0.36), as were
      waist and insulin sensitivity (r = -0.16). Both baseline waist and change in
      waist were significantly inversely associated with age 19 adiponectin but with
      age 19 insulin sensitivity only in men. In conclusion, in adolescents, the
      association between waist and adiponectin appears to develop several years before
      the association between waist and insulin sensitivity and there is a longitudinal
      association between waist and adiponectin. These results support the hypothesis
      that adiponectin may contribute to the association of waist and insulin
      sensitivity.

PMID- 19107129
TI  - Gender-ethnic disparity in BMI and waist circumference distribution shifts in US
      adults.
AB  - While obesity has been increasing in the United States, little is known about the
      variation in recent BMI and waist circumference (WC) distribution shifts across
      socio-demographic groups. We assessed shifts in BMI and WC distributions and
      compared between-group differences over the past decade, and projected future BMI
      and WC distributions and prevalence of obesity and central obesity using National
      Health and Nutrition Examination Survey (NHANES) 1988-1994 and 1999-2004 data.
      BMI/WC distributional shifts overall and in percentiles were compared across
      groups. Average yearly shift was calculated and used for projecting future
      distributions and prevalence. Both BMI and WC increased more in their uppermost
      percentile distribution, though BMI shift declined toward the uppermost
      percentiles among women. Heavier Americans gained more adiposity over the past
      decade. Ethnic (non-Hispanic (NH) white vs. black) disparities in mean BMI and WC
      became wider. Over the survey period, mean BMI increased by 1.3 units vs. 1.8
      units among men and women, whereas WC, by 4.2 cm vs. 4.8 cm. Young adults had the
      largest increase. Shift in women's WC was stable between the 25th and 75th
      percentiles, but gained pace at higher WC, while women's BMI and men's BMI and WC
      shifts increased linearly. NH black women had the largest shifts and would have
      central obesity and obesity prevalence of 90.8 and 70.7% by 2020. Shifts in BMI
      and WC distribution varied across age-, gender-, and ethnic groups. Future rise
      in the obesity and central obesity prevalence rates are expected, but would vary
      by demographic groups.

PMID- 19107130
TI  - Development and pilot evaluation of a complex intervention to improve experienced
      continuity of care in patients with cancer.
AB  - High experienced continuity of care in patients with cancer is associated with
      lower needs for care, better quality of life and better psychological outcomes.
      We developed and evaluated an intervention to improve experienced continuity. The
      intervention, consisted of (1) a 17-item patient-completed continuity assessment;
      (2) feedback to clinical nurse specialists and action to address the needs
      identified. Multidisciplinary team meetings and oncology outpatient clinics were
      observed, and patients and staff were interviewed. After qualitative work and
      reliability testing, the intervention was evaluated in a feasibility trial. Sixty
      one patients provided data for analysis. No statistically significant differences
      were found in patients' experienced continuity between the trial arms, but
      important trends were seen in measures of needs for care in favour of those
      receiving the intervention. Feeding back findings from the continuity assessment
      to clinicians reduced patients' needs for care. Our results indicate that an
      intervention to target patients' experiences of continuity can reduce their
      subsequent needs for care. However, overcoming barriers to organisational change
      and addressing some patients' hesitation to report their continuity difficulties
      must be considered when implementing such an intervention. A phase III trial
      targeting patients with inadequate experienced continuity of care is recommended.

PMID- 19107131
TI  - Cross talk between hedgehog and epithelial-mesenchymal transition pathways in
      gastric pit cells and in diffuse-type gastric cancers.
AB  - We previously reported hedgehog (Hh) signal activation in the mucus-secreting pit
      cell of the stomach and in diffuse-type gastric cancer (GC). Epithelial
      mesenchymal transition (EMT) is known to be involved in tumour malignancy.
      However, little is known about whether and how both signallings cooperatively act
      in diffuse-type GC. By microarray and reverse transcription-PCR, we investigated
      the expression of those Hh and EMT signalling molecules in pit cells and in
      diffuse-type GCs. How both signallings act cooperatively in those cells was also
      investigated by the treatment of an Hh-signal inhibitor and siRNAs of Hh and EMT
      transcriptional key regulator genes on a mouse primary culture and on human GC
      cell lines. Pit cells and diffuse-type GCs co-expressed many Hh and EMT
      signalling genes. Mesenchymal-related genes (WNT5A, CDH2, PDGFRB, EDNRA, ROBO1,
      ROR2, and MEF2C) were found to be activated by an EMT regulator,
      SIP1/ZFHX1B/ZEB2, which was a target of a primary transcriptional regulator GLI1
      in Hh signal. Furthermore, we identified two cancer-specific Hh targets, ELK1 and
      MSX2, which have an essential role in GC cell growth. These findings suggest that
      the gastric pit cell exhibits mesenchymal-like gene expression, and that diffuse
      type GC maintains expression through the Hh-EMT pathway. Our proposed extensive
      Hh-EMT signal pathway has the potential to an understanding of diffuse-type GC
      and to the development of new drugs.

PMID- 19107133
TI  - Cyclic Cushing syndrome due to an ectopic pituitary adenoma.
AB  - BACKGROUND: A 39-year-old man was referred to an endocrinology clinic for
      evaluation of his Cushing syndrome. He had gained 20 kg over 5 years and
      complained of intermittent headaches and easy bruisability. His medical history
      included a left foot fracture associated with minimal trauma 2 years earlier,
      hypertension, and stable Crohn disease with no use of exogenous glucocorticoids
      for at least 10 years. INVESTIGATIONS: Measurements of plasma adrenocorticotropic
      hormone, 24 h urine free cortisol excretion, late-night salivary cortisol, serum
      cortisol levels before and after corticotropin-releasing hormone administration
      during a dexamethasone suppression/corticotropin-releasing hormone-stimulation
      test, pituitary MRI, and inferior petrosal sinus sampling. DIAGNOSIS: Cyclic
      Cushing syndrome secondary to an ectopic pituitary adenoma. MANAGEMENT: The
      cyclic nature of Cushing syndrome was suggested by the absence of
      hypercortisolemia during inferior petrosal sinus sampling, and was confirmed by
      multiple 24 h urine free cortisol measurements. The patient underwent
      transsphenoidal surgery, during which a 5 mm firm, round, midline sphenoid sinus
      lesion was identified and resected. In preoperative imaging studies, this lesion
      had been interpreted as being a mucosal polyp. At microscopic examination, the
      lesion was found to be a pituitary adenoma, which stained diffusely with
      antiadrenocorticotropic-hormone antibodies. Explorations of the sella and
      pituitary did not reveal any abnormalities. Postoperatively, the patient became
      hypocortisolemic and his cushingoid features resolved. His adrenal function
      normalized 3 months after surgery. At 18 months, the patient continued to be
      symptom-free with normal levels of urinary-free cortisol and midnight salivary
      cortisol.

PMID- 19107135
TI  - Blockade of angiotensin II attenuates VEGF-mediated blood-retinal barrier
      breakdown in diabetic retinopathy.
AB  - Diabetic retinopathy (DR) is the leading cause of vision loss as a major
      complication of diabetes mellitus. The blood-retinal barrier (BRB) breakdown is a
      critical early event in the pathogenesis of DR. It has been known that the rennin
      angiotensin system (RAS) is important in the progression of the DR via
      angiotensin II (Ang II), the effector of RAS. In this study, we showed that
      blockade of Ang II attenuates vascular endothelial growth factor (VEGF)-mediated
      BRB breakdown in DR. In streptozotocin-induced diabetes, retinal vascular
      permeability increased with upregulation of VEGF, where Ang II and its receptors
      were upregulated. Ang II induced VEGF expression in retinal endothelial cells
      accompanied by loss of tight junction proteins. However, the blockade of Ang II
      by perindopril, an angiotensin converting enzyme (ACE) inhibitor, inhibited
      upregulation of VEGF, and prevented the loss of tight junction proteins.
      Moreover, inhibition of Ang II by perindopril attenuated increased vascular
      permeability of diabetic retina accompanied by recovery of tight junction
      proteins in retinal vessels. Therefore, we suggest that the RAS involves in
      increased vascular permeability during early stage of DR, which is mediated by
      VEGF. Furthermore, the ACE inhibitor may have a therapeutic potential in the
      treatment of diabetic BRB breakdown.

PMID- 19107134
TI  - Effect of 20-HETE inhibition on infarct volume and cerebral blood flow after
      transient middle cerebral artery occlusion.
AB  - This study examined the effects of an inhibitor of 20-hydroxyeicosatetraenoic
      acid (20-HETE) synthesis, N-(3-chloro-4-morpholin-4-yl)phenyl-N'-hydroxyimido
      formamide (TS-011), on infarct volume, volume at risk, cerebral blood flow (CBF),
      and levels of cytochrome P450 (CYP450) eicosanoids in the brain after transient
      occlusion of the middle cerebral artery (t-MCAO) in rats. TS-011 (0.1 mg/kg, iv)
      reduced cortical infarct volume by approximately 70% and total infarct volume by
      55%. TS-011 had no effect on the volume at risk or CBF during or up to 30 mins
      after the ischemic period. TS-011 reduced the delayed fall in CBF seen 2 h after
      reperfusion. The levels of CYP450 eicosanoids were similar in the ischemic and
      contralateral hemispheres after t-MCAO. TS-011 reduced 20-HETE levels in cerebral
      tissue by 80% but had no effect on the levels of EETs. Administration of another
      20-HETE inhibitor, HET0016 (0.01 to 1.0 mg/kg, iv) or a 20-HETE antagonist 20
      hydroxyeicosa-6(Z),15(Z)-dienoic acid (10 mg/kg, iv) also reduced infarct size.
      These results indicate that inhibitors of the synthesis or vasoconstrictor
      effects of 20-HETE reduce infarct size in rats after cerebral ischemia. The
      effects of TS-011 are not associated with changes in the area at risk or CBF and
      may be because of a potential protective effect in neurons subjected to ischemic
      stress.

PMID- 19107136
TI  - Mucosal tolerance to E-selectin promotes the survival of newly generated
      neuroblasts via regulatory T-cell induction after stroke in spontaneously
      hypertensive rats.
AB  - Neuroblasts in the subventricular zone (SVZ) proliferate markedly after brain
      ischemia, and migrate to the site of injury along with blood vessels. However, a
      large fraction of stroke-generated neuroblasts die shortly after being born, in
      part, because of local inflammation. In spontaneously hypertensive rats (SHRs)
      subjected to permanent middle cerebral artery occlusion, we primed E-selectin
      specific regulatory T cells (Tregs) by repetitive intranasal administration of
      recombinant E-selectin to target local secretion of immunomodulating,
      antiinflammatory cytokines to activating blood vessel segments. E-selectin
      tolerized SHRs had decreased infarction volumes, and increased numbers of Tregs
      in the cervical lymph nodes and ischemic brain. The brain Tregs were distributed
      primarily in periinfarct regions. E-selectin tolerization did not alter cellular
      proliferation in the ipsilateral SVZ after stroke, but the expression of tumor
      necrosis factor on vascular niche blood vessels was suppressed and both
      doublecortin protein levels and the number of newly generated neuroblasts or
      neurons were increased in the brain. This enhanced survival of neural progenitor
      cells and neurons was paralleled by improved functional performance. These
      studies suggest that E-selectin-specific Tregs can modulate the efficacy of
      neurogenesis after ischemia and promote repair after brain injury.

PMID- 19107137
TI  - Analysis of olive fly invasion in California based on microsatellite markers.
AB  - The olive fruit fly, Bactrocera oleae, is the main pest of the olive fruit and
      its expansion is exclusively restricted to the cultivation zone of the olive
      tree. Even though olive production has a century-old history in California, the
      olive fly was first detected in the Los Angeles area in 1998. Within 5 years of
      the first observation, the insect was reported from all olive cultivation areas
      of the state. Field-collected flies from five locations in California and another
      from Israel were analyzed on the basis of microsatellite polymorphisms in 10
      microsatellite loci. These results were integrated with those of a previous study
      of olive fly populations around the European part of the Mediterranean basin. The
      analysis pointed to the eastern part of the Mediterranean as the putative source
      of the observed invasion. Moreover, samples from California were quite different
      from Mediterranean samples implying the participation of phenomena such as
      genetic drift during the invasion and expansion of the olive fly in California.

PMID- 19107138
TI  - Molecular evolution of cytochrome b in high- and low-altitude deer mice (genus
      Peromyscus).
AB  - Patterns of amino-acid polymorphism in human mitochondrial genes have been
      interpreted as evidence for divergent selection among populations that inhabit
      climatically distinct environments. If similar patterns are mirrored in other
      broadly distributed mammalian species, then adaptive modifications of
      mitochondrial protein function may be detected in comparisons among locally
      adapted populations of a single wide-ranging species, or among closely related
      species that have adapted to different environments. Here, we test for evidence
      of positive selection on cytochrome b variation within and among species of the
      ecologically diverse rodent genus Peromyscus. We used likelihood-based
      comparisons of synonymous and nonsynonymous substitution rates to test for
      evidence of divergent selection between high- and low-altitude haplogroups of the
      deer mouse, Peromyscus maniculatus. We also tested for evidence of divergent
      selection among different species of Peromyscus that inhabit different thermal
      environments. In contrast to the purported evidence for positive selection on
      mitochondrial proteins in humans and other nonhuman mammals, results of our tests
      suggest that the evolution of cytochrome b in Peromyscus is chiefly governed by
      purifying selection.

PMID- 19107139
TI  - Striving for excellence in peer review.

PMID- 19107141
TI  - Retinitis pigmentosa: cone photoreceptors starving to death.

PMID- 19107142
TI  - Sniffing out a function for prion proteins.

PMID- 19107143
TI  - Hyperactive interneurons impair learning in a neurofibromatosis model.

PMID- 19107144
TI  - Spikes are making waves in the visual cortex.

PMID- 19107145
TI  - Pulling an all-nighter.

PMID- 19107146
TI  - A targeted population carrier screening program for severe and frequent genetic
      diseases in Israel.
AB  - A national carrier screening program targeted at communities in which severe
      genetic diseases are present with a frequency higher than 1/1000 live births, has
      been in existence in Israel since 2002. Within the communities at risk, carrier
      screening is voluntary whereas genetic counseling and testing is provided free of
      charge. During the first 5 years of the program more than 13 000 tests were
      performed, and at the end of 2007 it was offered in 35 different
      localities/communities for a total of 36 diseases. Many of the couples identified
      to be at risk opted for prenatal diagnosis and in two cases an affected pregnancy
      was terminated. In some cases the couples declined prenatal diagnosis and two of
      those families gave birth to an affected child. Based on the experience learnt
      from this targeted screening program it appears that a knowledge-based, voluntary
      screening program operated within the community is an effective way to provide
      genetic services and test referrals. The community program directed toward
      couples in their reproductive period does not seem to have led to stigmatization
      at either the individual or the community level.

PMID- 19107147
TI  - Profound, prelingual nonsyndromic deafness maps to chromosome 10q21 and is caused
      by a novel missense mutation in the Usher syndrome type IF gene PCDH15.
AB  - We studied a consanguineous family (Family A) from the island of Newfoundland
      with an autosomal recessive form of prelingual, profound, nonsyndromic
      sensorineural hearing loss. A genome-wide scan mapped the deafness trait to 10q21
      22 (max LOD score of 4.0; D10S196) and fine mapping revealed a 16 Mb ancestral
      haplotype in deaf relatives. The PCDH15 gene was mapped within the critical
      region and was an interesting candidate because truncating mutations cause Usher
      syndrome type IF (USH1F) and two missense mutations have been previously
      associated with isolated deafness (DFNB23). Sequencing of the PCDH15 gene
      revealed 33 sequencing variants. Three of these variants were homozygous
      exclusively in deaf siblings but only one of them was not seen in ethnically
      matched controls. This novel c.1583 T>A transversion predicts an amino-acid
      substitution of a valine with an aspartic acid at codon 528 (V528D). Like the two
      DFNB23 mutations, the V528D mutation in Family A occurs in a highly conserved
      extracellular cadherin (EC) domain of PCDH15 and is predicted to be more
      deleterious than the previously identified DFNB23 missense mutations (R134G and
      G262D). Physical assessment, vestibular and visual function testing in deaf
      adults ruled out syndromic deafness because of Usher syndrome. This study
      validates the DFNB23 designation and supports the hypothesis that missense
      mutations in conserved motifs of PCDH15 cause nonsyndromic hearing loss. This
      emerging genotype-phenotype correlation in USH1F is similar to that in several
      other USH1 genes and cautions against a prognosis of a dual sensory loss in deaf
      children found to be homozygous for hypomorphic mutations at the USH1F locus.

PMID- 19107148
TI  - Treacher Collins syndrome: etiology, pathogenesis and prevention.
AB  - Treacher Collins syndrome (TCS) is a rare congenital disorder of craniofacial
      development that arises as the result of mutations in the TCOF1 gene, which
      encodes a nucleolar phosphoprotein known as Treacle. Individuals diagnosed with
      TCS frequently undergo multiple reconstructive surgeries, which are rarely fully
      corrective. Identifying potential avenues for rescue and/or repair of TCS depends
      on a profound appreciation of the etiology and pathogenesis of the syndrome.
      Recent research using animal models has not only determined the cellular basis of
      TCS but also, more importantly, unveiled a successful avenue for therapeutic
      intervention and prevention of the craniofacial anomalies observed in TCS.

PMID- 19107150
TI  - Acousto-optic wavefront sensing and reconstruction.
AB  - We employ an acousto-optic cell as a tunable-pitch wavefront sensor and study its
      performance. The index of refraction of two cross-standing waves forms, in the
      near field, an adjustable array of caustics. These caustics, similar to the
      lenslets used for Hartmann-Shack sensing, were measured to have an extended focal
      relief of 200 times their pitch. We discovered a strong interaction between the
      caustics and source speckle, so much so that we had to modulate the beam to
      reduce it. We measured ocular wavefronts at different frequencies and established
      the consistency and reliability of the reconstruction.

PMID- 19107151
TI  - Target-in-the-loop wavefront sensing and control with a Collett-Wolf beacon:
      speckle-average phase conjugation.
AB  - Adaptive optical systems for laser beam projection onto an extended target
      embedded in an optically inhomogeneous medium are considered. A new adaptive
      optics wavefront control technique--speckle-average (SA) phase conjugation--is
      introduced. In this technique mitigation of speckle effects related to laser beam
      scattering off the rough target surface is achieved by measuring the SA wavefront
      slopes of the target return wave using a conventional Shack-Hartmann wavefront
      sensor. For statistically representative speckle averaging we consider the
      generation of an incoherent light source, referred to here as a Collett-Wolf
      beacon, directly on the target surface using a rapid steering (scanning)
      auxiliary laser beam. Our numerical simulations and experiment show that control
      of the outgoing beam phase using SA phase conjugation can lead to efficient
      compensation of turbulence effects and results in an increase of the projected
      laser beam power density on a remote extended target. The impact of both target
      anisoplanatism and the Collett-Wolf beacon size on adaptive system performance is
      studied.

PMID- 19107149
TI  - Y-chromosomal evidence of the cultural diffusion of agriculture in Southeast
      Europe.
AB  - The debate concerning the mechanisms underlying the prehistoric spread of farming
      to Southeast Europe is framed around the opposing roles of population movement
      and cultural diffusion. To investigate the possible involvement of local people
      during the transition of agriculture in the Balkans, we analysed patterns of Y
      chromosome diversity in 1206 subjects from 17 population samples, mainly from
      Southeast Europe. Evidence from three Y-chromosome lineages, I-M423, E-V13 and J
      M241, make it possible to distinguish between Holocene Mesolithic forager and
      subsequent Neolithic range expansions from the eastern Sahara and the Near East,
      respectively. In particular, whereas the Balkan microsatellite variation
      associated to J-M241 correlates with the Neolithic period, those related to E-V13
      and I-M423 Balkan Y chromosomes are consistent with a late Mesolithic time frame.
      In addition, the low frequency and variance associated to I-M423 and E-V13 in
      Anatolia and the Middle East, support an European Mesolithic origin of these two
      clades. Thus, these Balkan Mesolithic foragers with their own autochthonous
      genetic signatures, were destined to become the earliest to adopt farming, when
      it was subsequently introduced by a cadre of migrating farmers from the Near
      East. These initial local converted farmers became the principal agents spreading
      this economy using maritime leapfrog colonization strategies in the Adriatic and
      transmitting the Neolithic cultural package to other adjacent Mesolithic
      populations. The ensuing range expansions of E-V13 and I-M423 parallel in space
      and time the diffusion of Neolithic Impressed Ware, thereby supporting a case of
      cultural diffusion using genetic evidence.

PMID- 19107152
TI  - Advanced image processing and wavefront sensing with real-time phase diversity.
AB  - This paper will describe a state-of-the-art approach to real-time wavefront
      sensing and image enhancement. It will explore Boeing's existing technology to
      realize a 50 Hz frame rate (with a path to 1 KHz and higher). At this higher
      rate, phase diversity will be readily applicable to compensate for distortions of
      large dynamic bandwidth such as those of the atmosphere. We will describe various
      challenges in aligning a two-camera phase diversity system. Such configurations
      make it almost impossible to process the captured images without additional
      upgrade in the algorithm to account for alignment errors. An example of an error
      is the relative misalignment of the two images, the "best-focus" and the
      diversity image, where it is extremely hard to maintain alignment to less than a
      fraction of 1 pixel. We will show that the algorithm performance increases
      dramatically when we account for these errors in the estimation process.
      Preliminary evaluation has assessed a National Imagery Interpretability Rating
      Scale increase of approximately 3 from the best-focus to the enhanced image. Such
      a performance improvement would greatly increase the operating range (or,
      equivalently, decrease the weight) of many optical systems.

PMID- 19107153
TI  - Effect of anisoplanatism on the measurement accuracy of an extended-source
      Hartmann-Shack wavefront sensor.
AB  - We analyze the effect of anisoplanatic atmospheric turbulence on the measurement
      accuracy of an extended-source Hartmann-Shack wavefront sensor (HSWFS). We have
      numerically simulated an extended-source HSWFS, using a scenery of the solar
      surface that is imaged through anisoplanatic atmospheric turbulence and imaging
      optics. Solar extended-source HSWFSs often use cross-correlation algorithms in
      combination with subpixel shift finding algorithms to estimate the wavefront
      gradient, two of which were tested for their effect on the measurement accuracy.
      We find that the measurement error of an extended-source HSWFS is governed mainly
      by the optical geometry of the HSWFS, employed subpixel finding algorithm, and
      phase anisoplanatism. Our results show that effects of scintillation
      anisoplanatism are negligible when cross-correlation algorithms are used.

PMID- 19107154
TI  - Deep turbulence effects compensation experiments with a cascaded adaptive optics
      system using a 3.63 m telescope.
AB  - Compensation of extended (deep) turbulence effects is one of the most challenging
      problems in adaptive optics (AO). In the AO approach described, the deep
      turbulence wave propagation regime was achieved by imaging stars at low elevation
      angles when image quality improvement with conventional AO was poor. These
      experiments were conducted at the U.S. Air Force Maui Optical and Supercomputing
      Site (AMOS) by using the 3.63 m telescope located on Haleakala, Maui. To enhance
      compensation performance we used a cascaded AO system composed of a conventional
      AO system based on a Shack-Hartmann wavefront sensor and a deformable mirror with
      941 actuators, and an AO system based on stochastic parallel gradient descent
      optimization with four deformable mirrors (75 control channels). This first-time
      field demonstration of a cascaded AO system achieved considerably improved
      performance of wavefront phase aberration compensation. Image quality was
      improved in a repeatable way in the presence of stressing atmospheric conditions
      obtained by using stars at elevation angles as low as 15 degrees.

PMID- 19107155
TI  - Sub-aperture piston phase diversity for segmented and multi-aperture systems.
AB  - Phase diversity is a method of image-based wavefront sensing that simultaneously
      estimates the unknown phase aberrations of an imaging system along with an image
      of the object. To perform this estimation a series of images differing by a known
      aberration, typically defocus, are used. In this paper we present a new method of
      introducing the diversity unique to segmented and multi-aperture systems in which
      individual segments or sub-apertures are pistoned with respect to one another. We
      compare this new diversity with the conventional focus diversity.

PMID- 19107156
TI  - Closure phase and lucky imaging.
AB  - Since its introduction by Jennison in 1958, the closure-phase method for removing
      the effects of electrical path-length errors in radio astronomy and of
      atmospheric turbulence in optical astronomy has been based on the non-redundant
      spacing triple interferometer. It is shown that through application of lucky
      imaging concepts it is possible to relax this condition, making closure-phase
      methods possible with redundantly spaced interferometer configurations and
      thereby widening their range of application. In particular, a quadruple
      interferometer can, under lucky imaging conditions, be treated as though it were
      a triple interferometer. The slit-annulus aperture is investigated as a special
      case.

PMID- 19107157
TI  - Lucky imaging and aperture synthesis with low-redundancy apertures.
AB  - Lucky imaging, used with some success in astronomical and even horizontal-path
      imaging, relies on fleeting conditions of the atmosphere that allow momentary
      improvements in image quality, at least in portions of an image. Aperture
      synthesis allows a larger aperture and, thus, a higher-resolution imaging system
      to be synthesized through the superposition of image spatial-frequency components
      gathered by cooperative combinations of smaller subapertures. A combination of
      lucky imaging and aperture synthesis strengthens both methods for obtaining
      improved images through the turbulent atmosphere. We realize the lucky imaging
      condition appropriate for aperture synthesis imaging for a pair of rectangular
      subapertures and demonstrate that this condition occurs when the signal energy
      associated with bandpass spatial-frequency components achieves its maximum value.

PMID- 19107158
TI  - Improving the system stability of a digital Shack-Hartmann wavefront sensor with
      a special lenslet array.
AB  - There has been very limited study on the stability of a Shack-Hartmann wavefront
      sensor (SHWS) since its emergence in the early 1970s. In this paper, through
      experimental study of the system stability of a digital SHWS, a special lenslet
      array with long focal range is designed and implemented with a spatial light
      modulator to improve the system performance. Diffractive lenses with long focal
      length range can provide pseudo-nondiffracting beams and a long range of focusing
      plane. The performance and effect of the modified SHWS with this lenslet array
      are investigated, and the experimental results show that the system stability and
      measurement repeatability are not sensitive to the sensing distance and stay at
      an acceptable level.

PMID- 19107159
TI  - Fast and optimal multiframe blind deconvolution algorithm for high-resolution
      ground-based imaging of space objects.
AB  - We report a multiframe blind deconvolution algorithm that we have developed for
      imaging through the atmosphere. The algorithm has been parallelized to a
      significant degree for execution on high-performance computers, with an emphasis
      on distributed-memory systems so that it can be hosted on commodity clusters. As
      a result, image restorations can be obtained in seconds to minutes. We have
      compared and quantified the quality of its image restorations relative to the
      associated Cramer-Rao lower bounds (when they can be calculated). We describe the
      algorithm and its parallelization in detail, demonstrate the scalability of its
      parallelization across distributed-memory computer nodes, discuss the results of
      comparing sample variances of its output to the associated Cramer-Rao lower
      bounds, and present image restorations obtained by using data collected with
      ground-based telescopes.

PMID- 19107160
TI  - Influence of the source spectrum on the optical measurements of turbulence.
AB  - It is considered how the source spectrum influences the measurement accuracy of
      optical wave arrival angles, as well as the estimation of the path-averaged
      structure parameter of the refractive index fluctuations. Two reasons that can
      cause the wavelength dependence of the variance of fluctuations of wave arrival
      angles are analyzed. The first one is connected with the fact that phases depend
      on a wavelength in the approximation of smooth perturbations. The second reason
      is associated with the wavelength dependence of the refractive index and,
      consequently, its fluctuations. Strict equations are obtained to take into
      account the influence of the source spectrum on the measurement accuracy of the
      variance of arrival angle fluctuations and, indirectly, on the estimation
      accuracy of the path-averaged refractive index structure parameter. It can be
      stated that for most radiation sources (even nonmonochromatic) the influence of
      the source spectral composition can be neglected.

PMID- 19107161
TI  - Experimental comparison of tracking algorithms in the presence of aircraft
      boundary-layer distortions for emulated free-space laser communication links.
AB  - We report experiments comparing different focal plane array (FPA) tracking
      algorithms for emulated laser communication links between an aircraft and
      spacecraft. The links include look-angle-dependent phase disturbances caused by
      boundary-layer turbulence replicated by using a deformable mirror. Impairments
      from platform jitter, atmospheric scintillation, and propagation delay are also
      included. We study a hyperhemispherical dome geometry that provides a large field
      of regard but generates boundary-layer turbulence. Results from experiments
      comparing peak and centroid FPA tracking algorithms in various environments show
      that power delivered to the optical fiber varies with algorithm and look angle.
      An improvement in steady-state fiber-coupled power of up to 1.0 dB can be
      achieved through appropriate choice of algorithm. In a real system, this
      advantage could be realized by implementing a tracking processor that dynamically
      changes its tracking algorithm depending on look angle and other parameters
      correlated to boundary-layer turbulence.

PMID- 19107163
TI  - Dynamic response of ferrofluidic deformable mirrors.
AB  - Ferrofluids can be used to make deformable mirrors having highly interesting
      characteristics (e.g., extremely large strokes and low costs). Until recently,
      such mirrors were thought to be restricted to corrections of frequencies lower
      than 10 Hz, thus limiting their usefulness. We present counterintuitive results
      that demonstrate that the limiting operational frequency can be increased by
      increasing the viscosity of the ferrofluid. We tested the response of ferrofluids
      having viscosities as high as 494 cP, finding that they could allow an adaptive
      optics correction frequency as high as 900 Hz. We also demonstrate that we can
      counter the amplitude loss due to the high viscosity by overdriving the
      actuators. The overdriving technique combines high current, short duration pulses
      with ordinary driving step functions to deform the mirror. The integration of a
      FDM in a complete closed-loop adaptive optics system running at about 500 Hz thus
      appears to be a realistic goal in the near future.

PMID- 19107164
TI  - High average power 1.5 microm eye-safe Raman shifting in BaWO4 crystals.
AB  - A nanosecond 1.3 microm Nd:YAG laser-pumped external cavity eye-safe Raman laser
      based on BaWO(4) crystal is efficiently demonstrated. The average power of 1.5
      microm was 0.60 W operating at a pulse repetition rate of 1.7 kHz and an incident
      pump power of 4.14 W. Conversion efficiency of 14.5% and a high slope efficiency
      of 54.5% have been achieved. Pulse shortening was obviously observed. The pulse
      duration of the first Stokes was about 40 ns, much shorter than the fundamental
      pulse with a duration of approximately 220 ns.

PMID- 19107165
TI  - Aberration-corrected Czerny-Turner imaging spectrometer with a wide spectral
      region.
AB  - A modified asymmetrical Czerny-Turner arrangement with a fixed plane grating is
      proposed to correct aberrations over a wide spectral region by analysis of the
      dependence of aberration correction for different wavelengths. The principle and
      method of aberration correction are described in detail. We compare the
      performance of this modified Czerny-Turner arrangement with that of the existing
      Czerny-Turner arrangement by using a practical Czerny-Turner imaging spectrometer
      example.

PMID- 19107166
TI  - Polarization selection rules and optical transitions in terbium activated yttrium
      tantalate phosphor under x-ray, vacuum-ultraviolet, and ultraviolet excitations.
AB  - The terbium-activated yttrium tantalite (YTaO(4):Tb(3+)) phosphor is of great
      interest due to the interesting spectroscopic properties of rare earth ions in
      crystals and also practical use in x-ray imaging. Using the group-theoretical
      approach, we analyze the selection rules for the transition between Stark
      components of Tb(3+) in symmetry of the actual crystal field and the polarization
      for the allowed transitions. The luminescence upon UV, vacuum-ultraviolet (VUV),
      and x-ray excitation is presented and discussed. The YTaO(4):Tb(3+) phosphors are
      found to be efficient VUV-excited luminescent materials that could be used not
      only in x-ray intensifying screens, but also in mercury-free fluorescent lamps or
      plasma display panels.

PMID- 19107167
TI  - More on analyzing the reflection of a laser beam by a deformed highly reflective
      volume Bragg grating using iteration of the beam propagation method.
AB  - A further extension of the iteration method for beam propagation calculation is
      presented that can be applied for volume Bragg gratings (VBGs) with extremely
      large grating strength. A reformulation of the beam propagation formulation is
      presented for analyzing the reflection of a laser beam by a deformed VBG. These
      methods will be shown to be very accurate and efficient. A VBG with generic z
      dependent distortion has been analyzed using these methods.

PMID- 19107168
TI  - Combined reconstruction of fluorescent and optical parameters using time-resolved
      data.
AB  - We present an algorithm for simultaneous reconstruction of optical parameters,
      quantum yield, and lifetime in turbid media with embedded fluorescent inclusions.
      This algorithm is designed in the Fourier domain as an iterative solution of a
      system of differential equations of the Helmholtz type and does not involve full
      ill-conditioned matrix computations. The approach is based on allowing the
      unknown optical parameters, quantum yield, and lifetime to depend on the Fourier
      spectral parameter. The algorithm was applied to a time-gated experimental data
      set acquired by imaging a highly scattering cylindrical phantom concealing small
      fluorescent tubes. Relatively accurate reconstruction demonstrates the potential
      of the method.

PMID- 19107169
TI  - Continuous-wave 532 nm pumped MgO:PPLN optical parametric oscillator with
      external power regulation and spatial mode filtering.
AB  - We report a continuous-wave (CW) optical parametric oscillator (OPO) based on a
      MgO-doped periodically poled LiNbO(3) (MgO:PPLN) crystal. The 532 nm pump
      generates coherent radiation that is tunable from 800 to 920 nm for the signal
      and from 1250 to 1580 nm for the idler, respectively. The OPO output power
      exhibits a slowly varying instability that we attribute to a thermal effect
      induced by the pump. This instability is truncated by means of a low-pass servo
      that includes a single-mode fiber that filters the beam into a single spatial
      mode. The resulting output characteristics are promising for radiometric
      applications in the near infrared including most fiber-optic communication bands.

PMID- 19107170
TI  - Determination of surface tilt angle of splay and bend liquid crystal cells.
AB  - This study presents and demonstrates an approach for determining the surface tilt
      angles of parallel-aligned liquid crystal cells. The relationships between the
      incident angles and the corresponding phase retardations in the splay and the
      bend configurations are analyzed. The equations for the surface tilt angles are
      derived accordingly, and their accuracy is discussed. This method does not
      require knowledge of the cell thickness and is easily applied to assembled pi
      cells.

PMID- 19107171
TI  - Optimization of an optical configuration in a vertical alignment liquid crystal
      cell for wide viewing angle.
AB  - We propose an optical structure for a vertical alignment (VA) liquid crystal (LC)
      cell with a wide viewing angle. The proposed LC cell consists of an A-plate and
      two C-plates for optical compensation. Optical compensation and optimization to
      eliminate off-axis light leakage in the entire visible wavelength range are
      performed on a Poincare sphere using the Stokes vector and the Muller matrix
      method. After optimizing the wavelength dispersion of the retardation films that
      are used, we prove that the proposed VA LC cell can improve the viewing angle and
      contrast ratio by calculating optical characteristics, particularly in diagonal
      directions.

PMID- 19107172
TI  - Improved data search by zero-order (dc) peak filtering in a defocused volume
      holographic content-addressable memory.
AB  - Defocusing the recording material away from the Fourier plane is necessary to
      reduce the strong dc component and produce a more homogeneous object beam
      distribution in the hologram plane in volume holographic digital data-storage
      systems with amplitude-modulated data pages. However, content-addressable
      searching with defocused recording results in higher cross-correlation peak
      intensities. We present a method for performing a faithful content-addressable
      search in a defocused volume holographic data-storage system. A new dc-filtered
      content-addressable search method for defocused volume holographic data-storage
      systems with binary data pages is demonstrated. Both simulation and experimental
      results are presented. The experimental results show good discrimination
      capability and confirm the feasibility of the proposed technique.

PMID- 19107173
TI  - Self-aligned setup for laser optical feedback imaging insensitive to parasitic
      optical feedback.
AB  - We propose a new optical architecture for the laser optical feedback imaging
      (LOFI) technique which makes it possible to avoid the adverse effect of the
      optical parasitic backscattering introduced by all the optical interfaces located
      between the laser source and the studied object. This proposed setup needs no
      specific or complex alignment, which is why we can consider the proposed setup to
      be self-aligned. We describe the principle used to avoid the parasitic
      backscattering contributions that dramatically deteriorate amplitude and phase
      information contained in the LOFI images. Finally, we give a successful
      demonstration of amplitude and phase images obtained with this self-aligned setup
      in the presence of a parasitic reflection.

PMID- 19107174
TI  - Surface profile control of the autocloned photonic crystal by ion-beam-sputter
      deposition with radio-frequency-bias etching.
AB  - Growth of the autocloned Ta(2)O(5)/SiO(2) multilayer photonic crystal with a
      lateral sawtooth period was simulated. Ion-beam sputter (IBS) was applied to
      deposit the films and radio-frequency-bias (RF-bias) etching was applied
      simultaneously with the IBS on the Ta(2)O(5) film. Both simulation and experiment
      showed that the quality of the autocloning can be controlled by the RF-bias
      power; there is an intermediate power range within which the drop of peak-to
      valley height variation of the sawtooth profile can be reduced significantly such
      that a high degree of autocloning can be achieved. Analysis showed that
      simultaneous deposition and etching at the proper RF-bias power on the Ta(2)O(5)
      film has the capability to compensate the flattening effect of the SiO(2)
      deposition such that the sawtooth surface profile can be maintained.

PMID- 19107175
TI  - Switchable polarization-independent liquid-crystal Fabry-Perot filter.
AB  - A new approach to a polarization-independent twisted liquid-crystal (LC)
      structure, where phase difference between orthogonal eigenmodes is tuned to be an
      integer multiple of 2pi, is demonstrated with a numerical model. For select
      wavelengths, polarization-independent operation can be achieved by tuning the
      twist rate and thickness of the LC cavity. Applications can be found in
      polarization- independent switches and field sequential wavelength selection
      devices.

PMID- 19107176
TI  - Speckle suppression in scanning laser displays: aberration and defocusing of the
      projection system.
AB  - Aberration and defocusing effects in the mechanism of speckle suppression in
      laser projection displays were studied using the Fresnel approximation and the
      thin lens model. The analysis was performed with the assumption that aberrations
      change only the phase (and not the amplitude) in the rear principal plane of the
      display projection system. The analysis showed that aberrations should not have
      any influence on speckle contrast. It also showed that a screen shift relative to
      the image plane (defocusing) results only in a rescaling of the scanning beam
      autocorrelation function, which is equivalent to refocusing the objective lens to
      a new position of the screen. The optimal beam shape for optimal speckle
      suppression was also studied. A homogeneous field intensity distribution in the
      spatial frequency domain was found to provide close to the best speckle
      suppression.

PMID- 19107177
TI  - Feasibility study of the iterative x-ray phase retrieval algorithm.
AB  - An iterative phase retrieval algorithm was previously investigated for in-line x
      ray phase imaging. Through detailed theoretical analysis and computer
      simulations, we now discuss the limitations, robustness, and efficiency of the
      algorithm. The iterative algorithm was proved robust against imaging noise but
      sensitive to the variations of several system parameters. It is also efficient in
      terms of calculation time. It was shown that the algorithm can be applied to
      phase retrieval based on one phase-contrast image and one attenuation image, or
      two phase-contrast images; in both cases, the two images can be obtained either
      by one detector in two exposures, or by two detectors in only one exposure as in
      the dual-detector scheme.

PMID- 19107178
TI  - Measurement uncertainty evaluation for emission color and luminance of displays.
AB  - We present a measurement uncertainty evaluation for emission color and luminance
      of displays. The calibration procedures and the measurement uncertainties of a
      CCD-based spectroradiometer and a filter-type luminance meter are discussed. As
      evaluation examples, a Commission Internationale de l' Eclairage illuminant A, a
      liquid-crystal display with a light-emitting diode backlight, and a liquid
      crystal display with a cold-cathode fluorescent lamp backlight are evaluated. The
      uncertainties in Commission Internationale de l' Eclairage 1931 (x,y)
      chromaticity coordinates are determined to be in a range from 0.0020 to 0.0050
      (k=2). The uncertainties in luminance are obtained from 4.8% to 8.5% by using the
      spectroradiometer, while the filter-type luminance meter shows the uncertainties
      from 1.1% to 1.6% (k=2).

PMID- 19107179
TI  - Continuous-wave theory of Yb:YAG end-pumped thin-disk lasers.
AB  - The fundamental principles of the operation of a thin-disk laser are presented.
      We derived equations from a set of coupled rate equations that predict that the
      characteristics of a laser are affected by the Boltzmann occupation factors of
      the pump and the laser states simultaneously. The model is used to investigate
      the influence of the effective parameters on the operational efficiency of an end
      pumped Yb:YAG disk laser. Based on our results, we examined laser output power as
      a function of output coupler reflectivity, crystal thickness or doping
      concentration, number of the pump beam passes, and temperature.

PMID- 19107180
TI  - Single-scattering properties of triaxial ellipsoidal particles for a size
      parameter range from the Rayleigh to geometric-optics regimes.
AB  - The single-scattering properties of randomly oriented triaxial ellipsoids with
      size parameters from the Rayleigh to geometric-optics regimes are investigated. A
      combination of the discrete dipole approximation (DDA) technique and an improved
      geometric optics method (IGOM) is applied to the computation of ellipsoidal
      particle scattering properties for a complete range of size parameters. Edge
      effect contributions to the extinction and absorption efficiencies are included
      in the present IGOM simulation. It is found that the extinction efficiency,
      single-scattering albedo, and asymmetry factor computed from the DDA method for
      small size parameters smoothly transition to those computed from the IGOM for
      moderate-to-large size parameters. The phase matrix elements computed from these
      two methods are also quite similar when size parameters are larger than 30. Thus,
      the optical properties of ellipsoidal particles can be computed by combing the
      DDA and the IGOM for small-to-large size parameters. Furthermore, we also examine
      the applicability of the ellipsoid model to the simulation of the scattering
      properties of realistic aerosol particles by comparing the theoretical and
      experimental results for feldspar aerosols. It is shown that the ellipsoid model
      is better than the commonly used spheroid model for simulating dust particle
      optical properties, particularly, their polarization characteristics,
      realistically.

PMID- 19107181
TI  - Optical properties and microstructure of Ta2O5 biaxial film.
AB  - This study investigates the optical properties and microstructure of Ta(2)O(5)
      film deposited with the glancing angle deposition technique. The tilted
      nanocolumn microstructure, examined with scanning electron microscopy, induces
      the optical anisotropy of thin film. The optical properties of thin film are
      characterized with an inverse synthesis method. Based on the Cauchy model, the
      dispersion equations of optical constants of film are determined from the
      transmittance spectra measured at normal and oblique incidence over 400-800 nm.
      The starting values derived with an envelope method quicken the optimization
      process greatly. The dispersion of the principal indices N(1), N(2), and N(3) and
      the thickness d of thin film are presented statistically. A good agreement
      between the measured optical properties and theoretical calculation is obtained,
      which validates the model established for thin film produced by glancing angle
      deposition.

PMID- 19107182
TI  - Optical image coding with a circular Dammann grating.
AB  - A circular Dammann grating in the front focal plane of a lens is used to generate
      an annular beam in the back focal plane to code an object by two-dimensional
      scanning. The coded image of the object is decoded digitally by convolving it
      with the same annular beam used to code the object. Simple inverse filtering is
      subsequently used to improve the contrast of the decoded image.

PMID- 19107183
TI  - Laser Doppler sensor employing a single fan-shaped interference fringe system for
      distance and shape measurement of laterally moving objects.
AB  - For monitoring the position and shape of fast moving and, especially, rotating
      objects such as turbo machine rotors, contactless and compact sensors with a high
      measurement rate as well as high precision are required. We present for the first
      time, to the best of our knowledge, a novel laser Doppler sensor employing a
      single fan-shaped interference fringe system, which allows measuring for the
      position and shape of fast moving solid bodies with known tangential velocity. It
      is shown theoretically as well as experimentally that this sensor offers
      concurrently high position resolution and high temporal resolution in contrast to
      conventional measurement techniques, since its measurement uncertainty is, in
      principle, independent of the object velocity. Moreover, it can be built very
      compact, because it features low complexity. To prove its operational capability
      and its potential for practical applications, radial and axial shape measurements
      of rotating bodies are demonstrated in comparison with triangulation. An average
      position resolution of about 2 microm could be achieved.

PMID- 19107184
TI  - Delay Analysis of GTS Bridging between IEEE 802.15.4 and IEEE 802.11 Networks for
      Healthcare Applications.
AB  - We consider interconnection of IEEE 802.15.4 beacon-enabled network cluster with
      IEEE 802.11b network. This scenario is important in healthcare applications where
      IEEE 802.15.4 nodes comprise patient's body area network (BAN) and are involved
      in sensing some health-related data. BAN nodes have very short communication
      range in order to avoid harming patient's health and save energy. Sensed data
      needs to be transmitted to an access point in the ward room using wireless
      technology with higher transmission range and rate such as IEEE 802.11b. We model
      the interconnected network where IEEE 802.15.4-based BAN operates in guaranteed
      time slot (GTS) mode, and IEEE 802.11b part of the bridge conveys GTS superframe
      to the 802.11b access point. We then analyze the network delays. Performance
      analysis is performed using EKG traffic from continuous telemetry, and we discuss
      the delays of communication due the increasing number of patients.

PMID- 19107185
TI  - Gaze strategy in the free flying zebra finch (Taeniopygia guttata).
AB  - Fast moving animals depend on cues derived from the optic flow on their retina.
      Optic flow from translational locomotion includes information about the three
      dimensional composition of the environment, while optic flow experienced during a
      rotational self motion does not. Thus, a saccadic gaze strategy that segregates
      rotations from translational movements during locomotion will facilitate
      extraction of spatial information from the visual input. We analysed whether
      birds use such a strategy by highspeed video recording zebra finches from two
      directions during an obstacle avoidance task. Each frame of the recording was
      examined to derive position and orientation of the beak in three-dimensional
      space. The data show that in all flights the head orientation was shifted in a
      saccadic fashion and was kept straight between saccades. Therefore, birds use a
      gaze strategy that actively stabilizes their gaze during translation to simplify
      optic flow based navigation. This is the first evidence of birds actively
      optimizing optic flow during flight.

PMID- 19107186
TI  - Neanderthal extinction by competitive exclusion.
AB  - BACKGROUND: Despite a long history of investigation, considerable debate revolves
      around whether Neanderthals became extinct because of climate change or
      competition with anatomically modern humans (AMH). METHODOLOGY/PRINCIPAL
      FINDINGS: We apply a new methodology integrating archaeological and chronological
      data with high-resolution paleoclimatic simulations to define eco-cultural niches
      associated with Neanderthal and AMH adaptive systems during alternating cold and
      mild phases of Marine Isotope Stage 3. Our results indicate that Neanderthals and
      AMH exploited similar niches, and may have continued to do so in the absence of
      contact. CONCLUSIONS/SIGNIFICANCE: The southerly contraction of Neanderthal range
      in southwestern Europe during Greenland Interstadial 8 was not due to climate
      change or a change in adaptation, but rather concurrent AMH geographic expansion
      appears to have produced competition that led to Neanderthal extinction.

PMID- 19107187
TI  - Birds of a feather flock together: experience-driven formation of visual object
      categories in human ventral temporal cortex.
AB  - The present functional magnetic resonance imaging study provides direct evidence
      on visual object-category formation in the human brain. Although brain imaging
      has demonstrated object-category specific representations in the occipitotemporal
      cortex, the crucial question of how the brain acquires this knowledge has
      remained unresolved. We designed a stimulus set consisting of six highly similar
      bird types that can hardly be distinguished without training. All bird types were
      morphed with one another to create different exemplars of each category. After
      visual training, fMRI showed that responses in the right fusiform gyrus were
      larger for bird types for which a discrete category-boundary was established as
      compared with not-trained bird types. Importantly, compared with not-trained bird
      types, right fusiform responses were smaller for visually similar birds to which
      subjects were exposed during training but for which no category-boundary was
      learned. These data provide evidence for experience-induced shaping of
      occipitotemporal responses that are involved in category learning in the human
      brain.

PMID- 19107188
TI  - Male weaponry in a fighting cricket.
AB  - Sexually selected male weaponry is widespread in nature. Despite being model
      systems for the study of male aggression in Western science and for cricket
      fights in Chinese culture, field crickets (Orthoptera, Gryllidae, Gryllinae) are
      not known to possess sexually dimorphic weaponry. In a wild population of the
      fall field cricket, Gryllus pennsylvanicus, we report sexual dimorphism in head
      size as well as the size of mouthparts, both of which are used when aggressive
      contests between males escalate to physical combat. Male G. pennsylvanicus have
      larger heads, maxillae and mandibles than females when controlling for pronotum
      length. We conducted two experiments to test the hypothesis that relatively
      larger weaponry conveys an advantage to males in aggressive contests. Pairs of
      males were selected for differences in head size and consequently were different
      in the size of maxillae and mandibles. In the first experiment, males were
      closely matched for body size (pronotum length), and in the second, they were
      matched for body mass. Males with proportionately larger weaponry won more fights
      and increasing differences in weaponry size between males increased the fighting
      success of the male with the larger weaponry. This was particularly true when
      contests escalated to grappling, the most intense level of aggression. However,
      neither contest duration nor intensity was related to weaponry size as predicted
      by models of contest settlement. These results are the first evidence that the
      size of the head capsule and mouthparts are under positive selection via male
      male competition in field crickets, and validate 800-year-old Chinese traditional
      knowledge.

PMID- 19107189
TI  - The impact of changing medicaid enrollments on New Mexico's Immunization Program.
AB  - BACKGROUND: Immunizations are an important component to pediatric primary care.
      New Mexico is a relatively poor and rural state which has sometimes struggled to
      achieve and maintain its childhood immunization rates. We evaluated New Mexico's
      immunization rates between 1996 and 2006. Specifically, we examined the increase
      in immunization rates between 2002 and 2004, and how this increase may have been
      associated with Medicaid enrollment levels, as opposed to changes in government
      policies concerning immunization practices. METHODS AND FINDINGS: This study
      examines trends in childhood immunization coverage rates relative to Medicaid
      enrollment among those receiving Temporary Assistance for Needy Families (TANF)
      in New Mexico. Information on health policy changes and immunization coverage was
      obtained from state governmental sources and the National Immunization Survey. We
      found statistically significant correlations varying from 0.86 to 0.93 between
      immunization rates and Medicaid enrollment. CONCLUSIONS: New Mexico's improvement
      and subsequent deterioration in immunization rates corresponded with changing
      Medicaid coverage, rather than the state's efforts to change immunization
      practices. Maintaining high Medicaid enrollment levels may be important for
      achieving high childhood immunization levels.

PMID- 19107190
TI  - Norepinephrine controls both torpor initiation and emergence via distinct
      mechanisms in the mouse.
AB  - Some mammals, including laboratory mice, enter torpor in response to food
      deprivation, and leptin can attenuate these bouts of torpor. We previously showed
      that dopamine beta-hydroxylase knockout (Dbh -/-) mice, which lack norepinephrine
      (NE), do not reduce circulating leptin upon fasting nor do they enter torpor. To
      test whether the onset of torpor in mice during a fast requires a NE-mediated
      reduction in circulating leptin, double mutant mice deficient in both leptin
      (ob/ob) and DBH (DBL MUT) were generated. Upon fasting, control and ob/ob mice
      entered torpor as assessed by telemetric core T(b) acquisition. While fasting
      failed to induce torpor in Dbh -/- mice, leptin deficiency bypassed the
      requirement for NE, as DBL MUT mice readily entered torpor upon fasting. These
      data indicate that sympathetic activation of white fat and suppression of leptin
      is required for the onset of torpor in the mouse. Emergence from torpor was
      severely retarded in DBL MUT mice, revealing a novel, leptin-independent role for
      NE in torpor recovery. This phenotype was mimicked by administration of a beta(3)
      adrenergic receptor antagonist to control mice during a torpor bout. Hence, NE
      signaling via beta(3) adrenergic receptors presumably in brown fat is the first
      neurotransmitter-receptor system identified that is required for normal recovery
      from torpor.

PMID- 19107191
TI  - HSP60 as a target of anti-ergotypic regulatory T cells.
AB  - The 60 kDa heat shock protein (HSP60) has been reported to influence T-cell
      responses in two ways: as a ligand of toll-like receptor 2 signalling and as an
      antigen. Here we describe a new mechanism of T-cell immuno-regulation focused on
      HSP60: HSP60 is up-regulated and presented by activated T cells (HSP60 is an
      ergotope) to regulatory (anti-ergotypic) T cells. Presentation of HSP60 by
      activated T cells was found to be MHC-restricted and dependent on accessory
      molecules - CD28, CD80 and CD86. Anti-ergotypic T cells responded to T-cell HSP60
      by proliferation and secreted IFNgamma and TGFbeta1. In vitro, the anti-ergotypic
      T cells inhibited IFNgamma production by their activated T-cell targets. In vivo,
      adoptive transfer of an anti-ergotypic HSP60-specific T-cell line led to
      decreased secretion of IFNgamma by arthritogenic T cells and ameliorated adjuvant
      arthritis (AA). Thus, the presentation of HSP60 by activated T cells turns them
      into targets for anti-ergotypic regulatory T cells specific for HSP60. However,
      the direct interaction between the anti-ergotypic T regulators (anti-HSP60) and
      the activated T cells also down-regulated the regulators. Thus, by functioning as
      an ergotope, HSP60 can control both the effector T cells and the regulatory HSP60
      specific T cells that control them.

PMID- 19107192
TI  - A simple detection method for low-affinity membrane protein interactions by
      baculoviral display.
AB  - BACKGROUND: Membrane protein interactions play an important role in cell-to-cell
      recognition in various biological activities such as in the immune or neural
      system. Nevertheless, there has remained the major obstacle of expression of the
      membrane proteins in their active form. Recently, we and other investigators
      found that functional membrane proteins express on baculovirus particles (budded
      virus, BV). In this study, we applied this BV display system to detect
      interaction between membrane proteins important for cell-to-cell interaction in
      immune system. METHODOLOGY/PRINCIPAL FINDINGS: We infected Sf9 cells with
      recombinant baculovirus encoding the T cell membrane protein CD2 or its ligand
      CD58 and recovered the BV. We detected specific interaction between CD2
      displaying BV and CD58-displaying BV by an enzyme-linked immunosorbent assay
      (ELISA). Using this system, we also detected specific interaction between two
      other membrane receptor-ligand pairs, CD40-CD40 ligand (CD40L), and
      glucocorticoid-induced TNFR family-related protein (GITR)-GITR ligand (GITRL).
      Furthermore, we observed specific binding of BV displaying CD58, CD40L, or GITRL
      to cells naturally expressing their respective receptors by flowcytometric
      analysis using anti-baculoviral gp64 antibody. Finally we isolated CD2 cDNA from
      a cDNA expression library by magnetic separation using CD58-displaying BV and
      anti-gp64 antibody. CONCLUSIONS: We found the BV display system worked
      effectively in the detection of the interaction of membrane proteins. Since
      various membrane proteins and their oligomeric complexes can be displayed on BV
      in the native form, this BV display system should prove highly useful in the
      search for natural ligands or to develop screening systems for therapeutic
      antibodies and/or compounds.

PMID- 19107193
TI  - Lions and prions and deer demise.
AB  - BACKGROUND: Contagious prion diseases--scrapie of sheep and chronic wasting
      disease of several species in the deer family--give rise to epidemics that seem
      capable of compromising host population viability. Despite this prospect, the
      ecological consequences of prion disease epidemics in natural populations have
      received little consideration. METHODOLOGY/PRINCIPAL FINDINGS: Using a cohort
      study design, we found that prion infection dramatically lowered survival of free
      ranging adult (>2-year-old) mule deer (Odocoileus hemionus): estimated average
      life expectancy was 5.2 additional years for uninfected deer but only 1.6
      additional years for infected deer. Prion infection also increased nearly
      fourfold the rate of mountain lions (Puma concolor) preying on deer, suggesting
      that epidemics may alter predator-prey dynamics by facilitating hunting success.
      Despite selective predation, about one fourth of the adult deer we sampled were
      infected. High prevalence and low survival of infected deer provided a plausible
      explanation for the marked decline in this deer population since the 1980s.
      CONCLUSION: Remarkably high infection rates sustained in the face of intense
      predation show that even seemingly complete ecosystems may offer little
      resistance to the spread and persistence of contagious prion diseases. Moreover,
      the depression of infected populations may lead to local imbalances in food webs
      and nutrient cycling in ecosystems in which deer are important herbivores.

PMID- 19107194
TI  - Phosphorylation regulates SIRT1 function.
AB  - BACKGROUND: SIR2 is an NAD(+)-dependent deacetylase [1]-[3] implicated in the
      regulation of lifespan in species as diverse as yeast [4], worms [5], and flies
      [6]. We previously reported that the level of SIRT1, the mammalian homologue of
      SIR2 [7], [8], is coupled to the level of mitotic activity in cells both in vitro
      and in vivo[9]. Cells from long-lived mice maintained SIRT1 levels of young mice
      in tissues that undergo continuous cell replacement by proliferating stem cells.
      Changes in SIRT1 protein level were not associated with changes in mRNA level,
      suggesting that SIRT1 could be regulated post-transcriptionally. However, other
      than a recent report on sumoylation [10] and identification of SIRT1 as a nuclear
      phospho-protein by mass spectrometry [11], post-translational modifications of
      this important protein have not been reported. METHODOLOGY/PRINCIPAL FINDINGS: We
      identified 13 residues in SIRT1 that are phosphorylated in vivo using mass
      spectrometry. Dephosphorylation by phosphatases in vitro resulted in decreased
      NAD(+)-dependent deacetylase activity. We identified cyclinB/Cdk1 as a cell cycle
      dependent kinase that forms a complex with and phosphorylates SIRT1. Mutation of
      two residues phosphorylated by Cyclin B/Cdk1 (threonine 530 and serine 540)
      disturbs normal cell cycle progression and fails to rescue proliferation defects
      in SIRT1-deficient cells [12], [13]. CONCLUSIONS/SIGNIFICANCE: Pharmacological
      manipulation of SIRT1 activity is currently being tested as a means of extending
      lifespan in mammals. Treatment of obese mice with resveratrol, a pharmacological
      activator of SIRT1, modestly but significantly improved longevity and, perhaps
      more importantly, offered some protection against the development of type 2
      diabetes mellitus and metabolic syndrome [14]-[16]. Understanding the endogenous
      mechanisms that regulate the level and activity of SIRT1, therefore, has obvious
      relevance to human health and disease. Our results identify phosphorylation by
      cell cycle dependent kinases as a major mechanism controlling the level and
      function of this sirtuin and complement recent reports of factors that inhibit
      [17], [18] and activate [19] SIRT1 by protein-protein interactions.

PMID- 19107195
TI  - On the mechanics of cardiac function of Drosophila embryo.
AB  - The heart is a vital organ that provides essential circulation throughout the
      body. Malfunction of cardiac pumping, thus, leads to serious and most of the
      times, to fatal diseases. Mechanics of cardiac pumping is a complex process, and
      many experimental and theoretical approaches have been undertaken to understand
      this process. We have taken advantage of the simplicity of the embryonic heart of
      an invertebrate, Drosophila melanogaster, to understand the fundamental mechanics
      of the beating heart. We applied a live imaging technique to the beating
      embryonic heart combined with analytical imaging tools to study the dynamic
      mechanics of the pumping. Furthermore, we have identified one mutant line that
      exhibits aberrant pumping mechanics. The Drosophila embryonic heart consists of
      only 104 cardiac cells forming a simple straight tube that can be easily accessed
      for real-time imaging. Therefore, combined with the wealth of available genetic
      tools, the embryonic Drosophila heart may serve as a powerful model system for
      studies of human heart diseases, such as arrhythmia and congenital heart
      diseases. We, furthermore, believe our mechanistic data provides important
      information that is useful for our further understanding of the design of
      biological structure and function and for engineering the pumps for medical uses.

PMID- 19107196
TI  - Porphyrin homeostasis maintained by ABCG2 regulates self-renewal of embryonic
      stem cells.
AB  - BACKGROUND: Under appropriate culture conditions, undifferentiated embryonic stem
      (ES) cells can undergo multiple self-renewal cycles without loss of pluripotency
      suggesting they must be equipped with specific defense mechanisms to ensure
      sufficient genetic stability during self-renewal expansion. The ATP binding
      cassette transporter ABCG2 is expressed in a wide variety of somatic and
      embryonic stem cells. However, whether it plays an important role in stem cell
      maintenance remains to be defined. METHODOLOGY/PRINCIPAL FINDINGS: Here we
      provide evidence to show that an increase in the level of ABCG2 was observed
      accompanied by ES colony expansion and then were followed by decreases in the
      level of protoporphyrin IX (PPIX) indicating that ABCG2 plays a role in
      maintaining porphyrin homoeostasis. RNA-interference mediated inhibition of ABCG2
      as well as functional blockage of ABCG2 transporter with fumitremorgin C (FTC), a
      specific and potent inhibitor of ABCG2, not only elevated the cellular level of
      PPIX, but also arrest the cell cycle and reduced expression of the pluripotent
      gene Nanog. Overexpression of ABCG2 in ES cells was able to counteract the
      increase of endogenous PPIX induced by treatment with 5-Aminolevulinic acid
      suggesting ABCG2 played a direct role in removal of PPIX from ES cells. We also
      found that excess PPIX in ES cells led to elevated levels of reactive oxygen
      species which in turn triggered DNA damage signals as indicated by increased
      levels of gammaH2AX and phosphorylated p53. The increased level of p53 reduced
      Nanog expression because RNA- interference mediated inhibition of p53 was able to
      prevent the downregulation of Nanog induced by FTC treatment.
      CONCLUSIONS/SIGNIFICANCE: The present work demonstrated that ABCG2 protects ES
      cells from PPIX accumulation during colony expansion, and that p53 and gammaH2AX
      acts as a downstream checkpoint of ABCG2-dependent defense machinery in order to
      maintain the self-renewal of ES cells.

PMID- 19107197
TI  - Primordial germ cell specification from embryonic stem cells.
AB  - BACKGROUND: Primordial germ cell (PGC) specification is the first crucial step in
      germ line development. However, owing to significant challenges regarding the in
      vivo system, such as the complex cellular environment and potential problems with
      embryo manipulation, it is desirable to generate embryonic stem (ES) cells that
      are capable of overcoming these aforementioned limitations in order to provide a
      potential in vitro model to recapitulate the developmental processes in vivo.
      METHODOLOGY AND PRINCIPAL FINDINGS: Here, we studied the detailed process of PGC
      specification from stella-GFP ES cells. We first observed the heterogeneous
      expression of stella in ES cells. However, neither Stella-positive ES cells nor
      Stella-negative ES cells shared a similar gene expression pattern with either
      PGCs or PGC precursors. Second, we derived PGCs from ES cells using two
      differentiation methods, namely the attachment culture technique and the embryoid
      body (EB) method. Compared with PGCs derived via the attachment culture
      technique, PGCs derived via the EB method that had undergone the sequential
      erasure of Peg3 followed by Igf2r resulted in a cell line in which the expression
      dynamics of T, Fgf8 and Sox17, in addition to the expression of the epiblast
      markers, were more similar to the in vivo expression, thus demonstrating that the
      process of PGC derivation was more faithfully recapitulated using the EB method.
      Furthermore, we developed an in vitro model of PGC specification in a completely
      chemically defined medium (CDM) that indicated that BMP4 and Wnt3a promoted PGC
      derivation, whereas BMP8b and activinA had no observable effect on PGC
      derivation. CONCLUSIONS AND SIGNIFICANCE: The in vitro model we have established
      can recapitulate the developmental processes in vivo and provides new insights
      into the mechanism of PGC specification.

PMID- 19107198
TI  - The FERM and PDZ domain-containing protein tyrosine phosphatases, PTPN4 and
      PTPN3, are both dispensable for T cell receptor signal transduction.
AB  - PTPN3 and PTPN4 are two closely-related non-receptor protein tyrosine
      phosphatases (PTP) that, in addition to a PTP domain, contain FERM (Band 4.1,
      Ezrin, Radixin, and Moesin) and PDZ (PSD-95, Dlg, ZO-1) domains. Both PTP have
      been implicated as negative-regulators of early signal transduction through the T
      cell antigen receptor (TCR), acting to dephosphorylate the TCRzeta chain, a
      component of the TCR complex. Previously, we reported upon the production and
      characterization of PTPN3-deficient mice which show normal TCR signal
      transduction and T cell function. To address if the lack of a T cell phenotype in
      PTPN3-deficient mice can be explained by functional redundancy of PTPN3 with
      PTPN4, we generated PTPN4-deficient and PTPN4/PTPN3 double-deficient mice. As in
      PTPN3 mutants, T cell development and homeostasis and TCR-induced cytokine
      synthesis and proliferation were found to be normal in PTPN4-deficient and
      PTPN4/PTPN3 double-deficient mice. PTPN13 is another FERM and PDZ domain
      containing non-receptor PTP that is distantly-related to PTPN3 and PTPN4 and
      which has been shown to function as a negative-regulator of T helper-1 (Th1) and
      Th2 differentiation. Therefore, to determine if PTPN13 might compensate for the
      loss of PTPN3 and PTPN4 in T cells, we generated mice that lack functional forms
      of all three PTP. T cells from triple-mutant mice developed normally and showed
      normal cytokine secretion and proliferative responses to TCR stimulation.
      Furthermore, T cell differentiation along the Th1, Th2 and Th17 lineages was
      largely unaffected in triple-mutants. We conclude that PTPN3 and PTPN4 are
      dispensable for TCR signal transduction.

PMID- 19107199
TI  - A systematic survey of mini-proteins in bacteria and archaea.
AB  - BACKGROUND: Mini-proteins, defined as polypeptides containing no more than 100
      amino acids, are ubiquitous in prokaryotes and eukaryotes. They play significant
      roles in various biological processes, and their regulatory functions gradually
      attract the attentions of scientists. However, the functions of the majority of
      mini-proteins are still largely unknown due to the constraints of experimental
      methods and bioinformatic analysis. METHODOLOGY/PRINCIPAL FINDINGS: In this
      article, we extracted a total of 180,879 mini-proteins from the annotations of
      532 sequenced genomes, including 491 strains of Bacteria and 41 strains of
      Archaea. The average proportion of mini-proteins among all genomic proteins is
      approximately 10.99%, but different strains exhibit remarkable fluctuations.
      These mini-proteins display two notable characteristics. First, the majority are
      species-specific proteins with an average proportion of 58.79% among six
      representative phyla. Second, an even larger proportion (70.03% among all
      strains) is hypothetical proteins. However, a fraction of highly conserved
      hypothetical proteins potentially play crucial roles in organisms. Among mini
      proteins with known functions, it seems that regulatory and metabolic proteins
      are more abundant than essential structural proteins. Furthermore, domains in
      mini-proteins seem to have greater distributions in Bacteria than Eukarya.
      Analysis of the evolutionary progression of these domains reveals that they have
      diverged to new patterns from a single ancestor. CONCLUSIONS/SIGNIFICANCE: Mini
      proteins are ubiquitous in bacterial and archaeal species and play significant
      roles in various functions. The number of mini-proteins in each genome displays
      remarkable fluctuation, likely resulting from the differential selective
      pressures that reflect the respective life-styles of the organisms. The answers
      to many questions surrounding mini-proteins remain elusive and need to be
      resolved experimentally.

PMID- 19107200
TI  - Wind, waves, and wing loading: morphological specialization may limit range
      expansion of endangered albatrosses.
AB  - Among the varied adaptations for avian flight, the morphological traits allowing
      large-bodied albatrosses to capitalize on wind and wave energy for efficient long
      distance flight are unparalleled. Consequently, the biogeographic distribution of
      most albatrosses is limited to the windiest oceanic regions on earth; however,
      exceptions exist. Species breeding in the North and Central Pacific Ocean
      (Phoebastria spp.) inhabit regions of lower wind speed and wave height than
      southern hemisphere genera, and have large intrageneric variation in body size
      and aerodynamic performance. Here, we test the hypothesis that regional wind and
      wave regimes explain observed differences in Phoebastria albatross morphology and
      we compare their aerodynamic performance to representatives from the other three
      genera of this globally distributed avian family. In the North and Central
      Pacific, two species (short-tailed P. albatrus and waved P. irrorata) are
      markedly larger, yet have the smallest breeding ranges near highly productive
      coastal upwelling systems. Short-tailed albatrosses, however, have 60% higher
      wing loading (weight per area of lift) compared to waved albatrosses. Indeed,
      calculated aerodynamic performance of waved albatrosses, the only tropical
      albatross species, is more similar to those of their smaller congeners (black
      footed P. nigripes and Laysan P. immutabilis), which have relatively low wing
      loading and much larger foraging ranges that include central oceanic gyres of
      relatively low productivity. Globally, the aerodynamic performance of short
      tailed and waved albatrosses are most anomalous for their body sizes, yet
      consistent with wind regimes within their breeding season foraging ranges. Our
      results are the first to integrate global wind and wave patterns with albatross
      aerodynamics, thereby identifying morphological specialization that may explain
      limited breeding ranges of two endangered albatross species. These results are
      further relevant to understanding past and potentially predicting future
      distributional limits of albatrosses globally, particularly with respect to
      climate change effects on basin-scale and regional wind fields.

PMID- 19107201
TI  - Harmonic allocation of authorship credit: source-level correction of bibliometric
      bias assures accurate publication and citation analysis.
AB  - Authorship credit for multi-authored scientific publications is routinely
      allocated either by issuing full publication credit repeatedly to all coauthors,
      or by dividing one credit equally among all coauthors. The ensuing inflationary
      and equalizing biases distort derived bibliometric measures of merit by
      systematically benefiting secondary authors at the expense of primary authors.
      Here I show how harmonic counting, which allocates credit according to authorship
      rank and the number of coauthors, provides simultaneous source-level correction
      for both biases as well as accommodating further decoding of byline information.
      I also demonstrate large and erratic effects of counting bias on the original h
      index, and show how the harmonic version of the h-index provides unbiased
      bibliometric ranking of scientific merit while retaining the original's essential
      simplicity, transparency and intended fairness. Harmonic decoding of byline
      information resolves the conundrum of authorship credit allocation by providing a
      simple recipe for source-level correction of inflationary and equalizing bias.
      Harmonic counting could also offer unrivalled accuracy in automated assessments
      of scientific productivity, impact and achievement.

PMID- 19107202
TI  - Comparing platforms for C. elegans mutant identification using high-throughput
      whole-genome sequencing.
AB  - BACKGROUND: Whole-genome sequencing represents a promising approach to pinpoint
      chemically induced mutations in genetic model organisms, thereby short-cutting
      time-consuming genetic mapping efforts. PRINCIPAL FINDINGS: We compare here the
      ability of two leading high-throughput platforms for paired-end deep sequencing,
      SOLiD (ABI) and Genome Analyzer (Illumina; "Solexa"), to achieve the goal of
      mutant detection. As a test case we used a mutant C. elegans strain that harbors
      a mutation in the lsy-12 locus which we compare to the reference wild-type genome
      sequence. We analyzed the accuracy, sensitivity, and depth-coverage
      characteristics of the two platforms. Both platforms were able to identify the
      mutation that causes the phenotype of the mutant C. elegans strain, lsy-12. Based
      on a 4 MB genomic region in which individual variants were validated by Sanger
      sequencing, we observe tradeoffs between rates of false positives and false
      negatives when using both platforms under similar coverage and mapping criteria.
      SIGNIFICANCE: In conclusion, whole-genome sequencing conducted by either platform
      is a viable approach for the identification of single-nucleotide variations in
      the C. elegans genome.

PMID- 19107203
TI  - Direct inhibition of GSK3beta by the phosphorylated cytoplasmic domain of LRP6 in
      Wnt/beta-catenin signaling.
AB  - Wnt/beta-catenin signaling plays a central role in development and is also
      involved in a diverse array of diseases. Binding of Wnts to the coreceptors
      Frizzled and LRP6/5 leads to phosphorylation of PPPSPxS motifs in the LRP6/5
      intracellular region and the inhibition of GSK3beta bound to the scaffold protein
      Axin. However, it remains unknown how GSK3beta is specifically inhibited upon Wnt
      stimulation. Here, we show that overexpression of the intracellular region of
      LRP6 containing a Ser/Thr rich cluster and a PPPSPxS motif impairs the activity
      of GSK3beta in cells. Synthetic peptides containing the PPPSPxS motif strongly
      inhibit GSK3beta in vitro only when they are phosphorylated. Microinjection of
      these peptides into Xenopus embryos confirms that the phosphorylated PPPSPxS
      motif potentiates Wnt-induced second body axis formation. In addition, we show
      that the Ser/Thr rich cluster of LRP6 plays an important role in LRP6 binding to
      GSK3beta. These observations demonstrate that phosphorylated LRP6/5 both recruits
      and directly inhibits GSK3beta using two distinct portions of its cytoplasmic
      sequence, and suggest a novel mechanism of activation in this signaling pathway.

PMID- 19107205
TI  - Evidence of repeated and independent saltational evolution in a peculiar genus of
      sphinx moths (Proserpinus: Sphingidae).
AB  - BACKGROUND: Saltational evolution in which a particular lineage undergoes
      relatively rapid, significant, and unparalleled change as compared with its
      closest relatives is rarely invoked as an alternative model to the dominant
      paradigm of gradualistic evolution. Identifying saltational events is an
      important first-step in assessing the importance of this discontinuous model in
      generating evolutionary novelty. We offer evidence for three independent
      instances of saltational evolution in a charismatic moth genus with only eight
      species. METHODOLOGY/PRINCIPAL FINDINGS: Maximum parsimony, maximum likelihood
      and Bayesian search criteria offered congruent, well supported phylogenies based
      on 1,965 base pairs of DNA sequence using the mitochondrial gene cytochrome
      oxidase subunit I, and the nuclear genes elongation factor-1 alpha and wingless.
      Using a comparative methods approach, we examined three taxa exhibiting novelty
      in the form of Batesian mimicry, host plant shift, and dramatic physiological
      differences in light of the phylogenetic data. All three traits appear to have
      evolved relatively rapidly and independently in three different species of
      Proserpinus. Each saltational species exhibits a markedly different and discrete
      example of discontinuous trait evolution while remaining canalized for other
      typical traits shared by the rest of the genus. All three saltational taxa show
      insignificantly different levels of overall genetic change as compared with their
      congeners, implying that their divergence is targeted to particular traits and
      not genome-wide. CONCLUSIONS/SIGNIFICANCE: Such rapid evolution of novel traits
      in individual species suggests that the pace of evolution can be quick, dramatic,
      and isolated--even on the species level. These results may be applicable to other
      groups in which specific taxa have generated pronounced evolutionary novelty.
      Genetic mechanisms and methods for assessing such relatively rapid changes are
      postulated.

PMID- 19107204
TI  - Identification and characterization of novel microRNAs from Schistosoma
      japonicum.
AB  - BACKGROUND: Schistosomiasis japonica remains a major public health problem in
      China. Its pathogen, Schistosoma japonicum has a complex life cycle and a unique
      repertoire of genes expressed at different life cycle stages. Exploring
      schistosome gene regulation will yield the best prospects for new drug targets
      and vaccine candidates. MicroRNAs (miRNAs) are a highly conserved class of
      noncoding RNA that control many biological processes by sequence-specific
      inhibition of gene expression. Although a large number of miRNAs have been
      identified from plants to mammals, it remains no experimental proof whether
      schistosome exist miRNAs. METHODOLOGY AND RESULTS: We have identified novel
      miRNAs from Schistosoma japonicum by cloning and sequencing a small (18-26 nt)
      RNA cDNA library from the adult worms. Five novel miRNAs were identified from 227
      cloned RNA sequences and verified by Northern blot. Alignments of the miRNAs with
      corresponding family members indicated that four of them belong to a metazoan
      miRNA family: let-7, miR-71, bantam and miR-125. The fifth potentially new (non
      conserved) miRNA appears to belong to a previously undescribed family in the
      genus Schistosome. The novel miRNAs were designated as sja-let-7, sja-miR-71, sja
      bantam, sja-miR-125 and sja-miR-new1, respectively. Expression of sja-let-7, sja
      miR-71 and sja-bantam were analyzed in six stages of the life cycle, i.e. egg,
      miracidium, sporocyst, cercaria, schistosomulum, and adult worm, by a modified
      stem-loop reverse transcribed polymerase chain reaction (RT-PCR) method developed
      in our laboratory. The expression patterns of these miRNAs were highly stage
      specific. In particular, sja-miR-71 and sja-bantam expression reach their peaks
      in the cercaria stage and then drop quickly to the nadirs in the schistosomulum
      stage, following penetration of cercaria into a mammalian host. CONCLUSIONS:
      Authentic miRNAs were identified for the first time in S. japonicum, including a
      new schistosome family member. The different expression patterns of the novel
      miRNAs over the life stages of S. japonicum suggest that they may mediate
      important roles in Schistosome growth and development.

PMID- 19107206
TI  - Distinct genetic loci control plasma HIV-RNA and cellular HIV-DNA levels in HIV-1
      infection: the ANRS Genome Wide Association 01 study.
AB  - Previous studies of the HIV-1 disease have shown that HLA and Chemokine receptor
      genetic variants influence disease progression and early viral load. We performed
      a Genome Wide Association study in a cohort of 605 HIV-1-infected seroconverters
      for detection of novel genetic factors that influence plasma HIV-RNA and cellular
      HIV-DNA levels. Most of the SNPs strongly associated with HIV-RNA levels were
      localised in the 6p21 major histocompatibility complex (MHC) region and were in
      the vicinity of class I and III genes. Moreover, protective alleles for four
      disease-associated SNPs in the MHC locus (rs2395029, rs13199524, rs12198173 and
      rs3093662) were strikingly over-represented among forty-five Long Term HIV
      controllers. Furthermore, we show that the HIV-DNA levels (reflecting the HIV
      reservoir) are associated with the same four SNPs, but also with two additional
      SNPs on chromosome 17 (rs6503919; intergenic region flanked by the DDX40 and
      YPEL2 genes) and chromosome 8 (rs2575735; within the Syndecan 2 gene). Our data
      provide evidence that the MHC controls both HIV replication and HIV reservoir.
      They also indicate that two additional genomic loci may influence the HIV
      reservoir.

PMID- 19107207
TI  - Global expression profiling in atopic eczema reveals reciprocal expression of
      inflammatory and lipid genes.
AB  - BACKGROUND: Atopic eczema (AE) is a common chronic inflammatory skin disorder. In
      order to dissect the genetic background several linkage and genetic association
      studies have been performed. Yet very little is known about specific genes
      involved in this complex skin disease, and the underlying molecular mechanisms
      are not fully understood. METHODOLOGY/FINDINGS: We used human DNA microarrays to
      identify a molecular picture of the programmed responses of the human genome to
      AE. The transcriptional program was analyzed in skin biopsy samples from lesional
      and patch-tested skin from AE patients sensitized to Malassezia sympodialis (M.
      sympodialis), and corresponding biopsies from healthy individuals. The most
      notable feature of the global gene-expression pattern observed in AE skin was a
      reciprocal expression of induced inflammatory genes and repressed lipid
      metabolism genes. The overall transcriptional response in M. sympodialis patch
      tested AE skin was similar to the gene-expression signature identified in
      lesional AE skin. In the constellation of genes differentially expressed in AE
      skin compared to healthy control skin, we have identified several potential
      susceptibility genes that may play a critical role in the pathological condition
      of AE. Many of these genes, including genes with a role in immune responses,
      lipid homeostasis, and epidermal differentiation, are localized on chromosomal
      regions previously linked to AE. CONCLUSIONS/SIGNIFICANCE: Through genome-wide
      expression profiling, we were able to discover a distinct reciprocal expression
      pattern of induced inflammatory genes and repressed lipid metabolism genes in
      skin from AE patients. We found a significant enrichment of differentially
      expressed genes in AE with cytobands associated to the disease, and furthermore
      new chromosomal regions were found that could potentially guide future region
      specific linkage mapping in AE. The full data set is available at
      http://microarray-pubs.stanford.edu/eczema.

PMID- 19107208
TI  - Looking for myself: current multisensory input alters self-face recognition.
AB  - How do I know the person I see in the mirror is really me? Is it because I know
      the person simply looks like me, or is it because the mirror reflection moves
      when I move, and I see it being touched when I feel touch myself? Studies of face
      recognition suggest that visual recognition of stored visual features inform self
      face recognition. In contrast, body-recognition studies conclude that
      multisensory integration is the main cue to selfhood. The present study
      investigates for the first time the specific contribution of current multisensory
      input for self-face recognition. Participants were stroked on their face while
      they were looking at a morphed face being touched in synchrony or asynchrony.
      Before and after the visuo-tactile stimulation participants performed a self
      recognition task. The results show that multisensory signals have a significant
      effect on self-face recognition. Synchronous tactile stimulation while watching
      another person's face being similarly touched produced a bias in recognizing
      one's own face, in the direction of the other person included in the
      representation of one's own face. Multisensory integration can update cognitive
      representations of one's body, such as the sense of ownership. The present study
      extends this converging evidence by showing that the correlation of synchronous
      multisensory signals also updates the representation of one's face. The face is a
      key feature of our identity, but at the same time is a source of rich
      multisensory experiences used to maintain or update self-representations.

PMID- 19107209
TI  - An insight into the relationships between hepcidin, anemia, infections and
      inflammatory cytokines in pediatric refugees: a cross-sectional study.
AB  - BACKGROUND: Hepcidin, a key regulator of iron homeostasis, is increased in
      response to inflammation and some infections, but the in vivo role of hepcidin,
      particularly in children with iron deficiency anemia (IDA) is unclear. We
      investigated the relationships between hepcidin, cytokines and iron status in a
      pediatric population with a high prevalence of both anemia and co-morbid
      infections. METHODOLOGY/PRINCIPAL FINDINGS: African refugee children <16 years
      were consecutively recruited at the initial post-resettlement health check with
      181 children meeting inclusion criteria. Data on hematological parameters,
      cytokine levels and co-morbid infections (Helicobacter pylori, helminth and
      malaria) were obtained and urinary hepcidin assays performed. The primary outcome
      measure was urinary hepcidin levels in children with and without iron deficiency
      (ID) and/or ID anaemia (IDA). The secondary outcome measures included were the
      relationship between co-morbid infections and (i) ID and IDA, (ii) urinary
      hepcidin levels and (iii) cytokine levels. IDA was present in 25/181 (13.8%).
      Children with IDA had significantly lower hepcidin levels (IDA median hepcidin
      0.14 nmol/mmol Cr (interquartile range 0.05-0.061) versus non-IDA 2.96 nmol/mmol
      Cr, (IQR 0.95-6.72), p<0.001). Hemoglobin, log-ferritin, iron, mean cell volume
      (MCV) and transferrin saturation were positively associated with log-hepcidin
      levels (log-ferritin beta coefficient (beta): 1.30, 95% CI 1.02 to 1.57) and
      transferrin was inversely associated (beta: -0.12, 95% CI -0.15 to -0.08).
      Cytokine levels (including IL-6) and co-morbid infections were not associated
      with IDA or hepcidin levels. CONCLUSIONS/SIGNIFICANCE: This is the largest
      pediatric study of the in vivo associations between hepcidin, iron status and
      cytokines. Gastro-intestinal infections (H. pylori and helminths) did not elevate
      urinary hepcidin or IL-6 levels in refugee children, nor were they associated
      with IDA. Longitudinal and mechanistic studies of IDA will further elucidate the
      role of hepcidin in paediatric iron regulation.

PMID- 19107210
TI  - The effect of oxidant and the non-oxidant alteration of cellular thiol
      concentration on the formation of protein mixed-disulfides in HEK 293 cells.
AB  - Cellular molecules possess various mechanisms in responding to oxidant stress. In
      terms of protein responses, protein S-glutathionylation is a unique post
      translational modification of protein reactive cysteines forming disulfides with
      glutathione molecules. This modification has been proposed to play roles in
      antioxidant, regulatory and signaling in cells under oxidant stress. Recently,
      the increased level of protein S-glutathionylation has been linked with the
      development of diseases. In this report, specific S-glutathionylated proteins
      were demonstrated in human embryonic kidney 293 cells treated with two different
      oxidative reagents: diamide and hydrogen peroxide. Diamide is a chemical
      oxidizing agent whereas hydrogen peroxide is a physiological oxidant. Under the
      experimental conditions, these two oxidants decreased glutathione concentration
      without toxicity. S-glutathionylated proteins were detected by immunoblotting and
      glutathione concentrations were determined by high performance liquid
      chromatography. We further show the effect of alteration of the cellular thiol
      pool on the amount of protein S-glutathionylation in oxidant-treated cells.
      Cellular thiol concentrations were altered either by a specific way using
      buthionine sulfoximine, a specific inhibitor of glutathione biosynthesis or by a
      non-specific way, incubating cells in cystine-methionine deficient media. Cells
      only treated with either buthionine sulfoximine or cystine-methionine deficient
      media did not induce protein S-glutathionylation, even though both conditions
      decreased 65% of cellular glutathione. Moreover, the amount of protein S
      glutathionylation under both conditions in the presence of oxidants was not
      altered when compared to the amount observed in regular media with oxidants
      present. Protein S-glutathionylation is a dynamic reaction which depends on the
      rate of adding and removing glutathione. Phenylarsine oxide, which specifically
      forms a covalent adduct with vicinal thiols, was used to determine the possible
      role of vicinal thiols in the amount of glutathionylation. Our data shows
      phenylarsine oxide did not change glutathione concentrations, but it did enhance
      the amount of glutathionylation in oxidant-treated cells.

PMID- 19107211
TI  - Effectiveness of action to reduce exposure of free-ranging California condors in
      Arizona and Utah to lead from spent ammunition.
AB  - California condors (Gymnogyps californianus) released into the wild in Arizona
      ranged widely in Arizona and Utah. Previous studies have shown that the blood
      lead concentrations of many of the birds rise because of ingestion of spent lead
      ammunition. Condors were routinely recaptured and treated to reduce their lead
      levels as necessary but, even so, several died from lead poisoning. We used
      tracking data from VHF and satellite tags, together with the results of routine
      testing of blood lead concentrations, to estimate daily changes in blood lead
      level in relation to the location of each bird. The mean daily increment in blood
      lead concentration depended upon both the location of the bird and the time of
      year. Birds that spent time during the deer hunting season in two areas in which
      deer were shot with lead ammunition (Kaibab Plateau (Arizona) and Zion (Utah))
      were especially likely to have high blood lead levels. The influence upon blood
      lead level of presence in a particular area declined with time elapsed since the
      bird was last there. We estimated the daily blood lead level for each bird and
      its influence upon daily mortality rate from lead poisoning. Condors with high
      blood lead over a protracted period were much more likely to die than birds with
      low blood lead or short-term elevation. We simulated the effect of ending the
      existing lead exposure reduction measures at Kaibab Plateau, which encourage the
      voluntary use of non-lead ammunition and removal of gut piles of deer and elk
      killed using lead ammunition. The estimated mortality rate due to lead in the
      absence of this program was sufficiently high that the condor population would be
      expected to decline rapidly. The extension of the existing lead reduction program
      to cover Zion (Utah), as well as the Kaibab plateau, would be expected to reduce
      mortality caused by lead substantially and allow the condor population to
      increase.

PMID- 19107212
TI  - Long-term cycles in the history of life: periodic biodiversity in the
      paleobiology database.
AB  - Time series analysis of fossil biodiversity of marine invertebrates in the
      Paleobiology Database (PBDB) shows a significant periodicity at approximately 63
      My, in agreement with previous analyses based on the Sepkoski database. I discuss
      how this result did not appear in a previous analysis of the PBDB. The existence
      of the 63 My periodicity, despite very different treatment of systematic error in
      both PBDB and Sepkoski databases strongly argues for consideration of its reality
      in the fossil record. Cross-spectral analysis of the two datasets finds that a 62
      My periodicity coincides in phase by 1.6 My, equivalent to better than the errors
      in either measurement. Consequently, the two data sets not only contain the same
      strong periodicity, but its peaks and valleys closely correspond in time. Two
      other spectral peaks appear in the PBDB analysis, but appear to be artifacts
      associated with detrending and with the increased interval length. Sampling
      standardization procedures implemented by the PBDB collaboration suggest that the
      signal is not an artifact of sampling bias. Further work should focus on finding
      the cause of the 62 My periodicity.

PMID- 19107213
TI  - The inhibition of the highly expressed miR-221 and miR-222 impairs the growth of
      prostate carcinoma xenografts in mice.
AB  - BACKGROUND: MiR-221 and miR-222 are two highly homologous microRNAs whose
      upregulation has been recently described in several types of human tumors, for
      some of which their oncogenic role was explained by the discovery of their target
      p27, a key cell cycle regulator. We previously showed this regulatory
      relationship in prostate carcinoma cell lines in vitro, underlying the role of
      miR-221/222 as inducers of proliferation and tumorigenicity.
      METHODOLOGY/PRINCIPAL FINDINGS: Here we describe a number of in vivo approaches
      confirming our previous data. The ectopic overexpression of miR-221 is able, per
      se, to confer a high growth advantage to LNCaP-derived tumors in SCID mice.
      Consistently, the anti-miR-221/222 antagomir treatment of established
      subcutaneous tumors derived from the highly aggressive PC3 cell line, naturally
      expressing high levels of miR-221/222, reduces tumor growth by increasing
      intratumoral p27 amount; this effect is long lasting, as it is detectable as long
      as 25 days after the treatment. Furthermore, we provide evidence in favour of a
      clinical relevance of the role of miR-221/222 in prostate carcinoma, by showing
      their general upregulation in patient-derived primary cell lines, where we find a
      significant inverse correlation with p27 expression. CONCLUSIONS/SIGNIFICANCE:
      These findings suggest that modulating miR-221/222 levels may have a therapeutic
      potential in prostate carcinoma.

PMID- 19107215
TI  - Benchmarking the urology practice.
AB  - The medical practice today is relentlessly challenged by medical progress, by
      rising costs, and by the mounting pressures of the managed care environment. It
      should be the approach of every medical practice manager and practitioner to seek
      out and measure up to the best standards so as to optimize patient care and
      business outcomes. This requires the resolute pursuit of good models, brought
      about by the fostering of key collaborative relationships that are both practical
      and strategic. Integral to this process is benchmarking: the way by which
      information is obtained from both internal and external sources to determine and
      set the standards for performance. Benchmarking is an invaluable strategic tool.

PMID- 19107214
TI  - Genomic resources and tools for gene function analysis in potato.
AB  - Potato, a highly heterozygous tetraploid, is undergoing an exciting phase of
      genomics resource development. The potato research community has established
      extensive genomic resources, such as large expressed sequence tag (EST) data
      collections, microarrays and other expression profiling platforms, and large
      insert genomic libraries. Moreover, potato will now benefit from a global potato
      physical mapping effort, which is serving as the underlying resource for a full
      potato genome sequencing project, now well underway. These tools and resources
      are having a major impact on potato breeding and genetics. The genome sequence
      will provide an invaluable comparative genomics resource for cross-referencing to
      the other Solanaceae, notably tomato, whose sequence is also being determined.
      Most importantly perhaps, a potato genome sequence will pave the way for the
      functional analysis of the large numbers of potato genes that await discovery.
      Potato, being easily transformable, is highly amenable to the investigation of
      gene function by biotechnological approaches. Recent advances in the development
      of Virus Induced Gene Silencing (VIGS) and related methods will facilitate rapid
      progress in the analysis of gene function in this important crop.

PMID- 19107216
TI  - Antidiabetic rosiglitazone reduces soluble intercellular adhesion molecule-1
      level in type 2 diabetic patients with coronary artery disease.
AB  - Background. We investigated the level of soluble adhesion molecules in diabetic
      patients and the effect of the peroxisome proliferator-activated receptor-gamma
      (PPAR-gamma) agonist rosiglitazone on plasma levels of adhesion molecules and an
      inflammation marker in type 2 diabetic patients with coronary artery disease
      (CAD) after percutaneous coronary intervention (PCI). Methods. A total of 116
      diabetic patients with CAD who had undergone PCI were randomized to receive
      rosiglitazone (4 mg/d) or not for 6 months. Plasma levels of soluble
      intercellular adhesion molecules (sICAM-1) and P-selectin (sP-selectin) were
      measured on ELISA. Results. After 6-month rosiglitazone treatment, plasma levels
      of sICAM-1 were lower than baseline and control group levels (370.4 (332.4-421.9)
      pg/mL versus 423.5 (327.4-500.3) pg/mL and 404.6 (345.2-483.4) pg/mL, P < .001).
      In addition, plasma levels of C-reactive protein were significantly reduced from
      baseline levels. However, plasma level of sP-selectin was not significantly
      lowered with rosiglitazone treatment than with control treatment after 6-month
      follow-up. Conclusions. Rosiglitazone reduces chronic inflammatory responses and
      improves levels of markers of endothelial dysfunction in patients with diabetes
      and CAD. PPAR-gamma agonist may have a beneficial effect on the vascular
      endothelium through its anti-inflammatory mechanism and may be useful as therapy
      in patients undergoing PCI.

PMID- 19107217
TI  - Regulation of peroxisome proliferator-activated receptors by e6-associated
      protein.
AB  - Peroxisome proliferator-activated receptors (PPARs) are nuclear receptors (NRs)
      that regulate genes involved in lipid and glucose metabolism. PPAR activity is
      regulated by interactions with cofactors and of interest are cofactors with
      ubiquitin ligase activity. The E6-associated protein (E6-AP) is an E3 ubiquitin
      ligase that affects the activity of other NRs, although its effects on PPARs have
      not been examined. E6-AP inhibited the ligand-independent transcriptional
      activity of PPARalpha and PPARbeta, with marginal effects on PPARgamma, and
      decreased basal mRNA levels of PPARalpha target genes. Inhibition of PPARalpha
      activity required the ubiquitin ligase function of E6-AP, but occurred in a
      proteasome-independent manner. PPARalpha interacted with E6-AP, and in mice
      treated with PPARalpha agonist clofibrate, mRNA and protein levels of E6-AP were
      increased in wildtype, but not in PPARalpha null mice, indicating a PPARalpha
      dependent regulation. These studies suggest coordinate regulation of E6-AP and
      PPARalpha, and contribute to our understanding of the role of PPARs in cellular
      metabolism.

PMID- 19107218
TI  - Human polycomb 2 protein is a SUMO E3 ligase and alleviates substrate-induced
      inhibition of cystathionine beta-synthase sumoylation.
AB  - Human cystathionine beta-synthase (CBS) catalyzes the first irreversible step in
      the transsulfuration pathway and commits homocysteine to the synthesis of
      cysteine. Mutations in CBS are the most common cause of severe hereditary
      hyperhomocysteinemia. A yeast two-hybrid approach to screen for proteins that
      interact with CBS had previously identified several components of the sumoylation
      pathway and resulted in the demonstration that CBS is a substrate for
      sumoylation. In this study, we demonstrate that sumoylation of CBS is enhanced in
      the presence of human polycomb group protein 2 (hPc2), an interacting partner
      that was identified in the initial yeast two-hybrid screen. When the substrates
      for CBS, homocysteine and serine for cystathionine generation and homocysteine
      and cysteine for H(2)S generation, are added to the sumoylation mixture, they
      inhibit the sumoylation reaction, but only in the absence of hPc2. Similarly, the
      product of the CBS reaction, cystathionine, inhibits sumoylation in the absence
      of hPc2. Sumoylation in turn decreases CBS activity by approximately 28% in the
      absence of hPc2 and by 70% in its presence. Based on these results, we conclude
      that hPc2 serves as a SUMO E3 ligase for CBS, increasing the efficiency of
      sumoylation. We also demonstrate that gamma-cystathionase, the second enzyme in
      the transsulfuration pathway is a substrate for sumoylation under in vitro
      conditions. We speculate that the role of this modification may be for nuclear
      localization of the cysteine-generating pathway under conditions where nuclear
      glutathione demand is high.

PMID- 19107219
TI  - Keep your options open: an information-based driving principle for sensorimotor
      systems.
AB  - The central resource processed by the sensorimotor system of an organism is
      information. We propose an information-based quantity that allows one to
      characterize the efficiency of the perception-action loop of an abstract organism
      model. It measures the potential of the organism to imprint information on the
      environment via its actuators in a way that can be recaptured by its sensors,
      essentially quantifying the options available and visible to the organism.
      Various scenarios suggest that such a quantity could identify the preferred
      direction of evolution or adaptation of the sensorimotor loop of organisms.

PMID- 19107221
TI  - Closing the gaps in paediatric reference intervals: the CALIPER initiative.
AB  - Screening, diagnosis and monitoring of paediatric diseases relies on the
      measurement of a spectrum of disease biomarkers in clinical laboratories to guide
      important clinical decisions. Physicians rely on the availability of suitable and
      reliable reference intervals to accurately interpret laboratory test results with
      data collected during medical history and physical examination. However, critical
      gaps currently exist in accurate and up-to-date reference intervals (normal
      values) for accurate interpretation of laboratory tests performed in children and
      adolescents. These gaps in the available paediatric laboratory reference
      intervals have the clear potential of contributing to erroneous diagnosis or
      misdiagnosis of many diseases of childhood and adolescence. Most of the available
      reference intervals for laboratory tests were determined over two decades ago on
      older instruments and technologies, and are no longer relevant considering the
      current testing technology used by clinical laboratories. It is thus critical and
      of utmost urgency that a more acceptable and comprehensive database be
      established. There are however many challenges when attempting to establish
      paediatric reference intervals. Paediatric specimen collection is a major concern
      for health care providers as it is frequently difficult to obtain sufficient
      volumes of blood or urine from paediatric patients. Common reference intervals
      have not been widely implemented due to lack of harmonisation of methods and
      differences in patient populations. Consequently, clinical laboratory
      accreditation organisations and licensing agencies require that each laboratory
      verify or establish reference intervals for each method. To provide such
      reference intervals requires selection criteria for suitable reference
      individuals, defined conditions for specimen collection and analysis, method
      selection to determine reference limits and validation of the reference interval.
      The current review will provide a brief introduction to the current approach to
      establishment of reference intervals, will highlight the current gaps in data
      available in paediatric populations, and review a recent Canadian initiative,
      CALIPER (Canadian Laboratory Initiative on Paediatric Reference Intervals), to
      establish a comprehensive database for both traditional and emerging biomarkers
      of paediatric disease.

PMID- 19107222
TI  - An evidence-base for laboratory endocrinology?

PMID- 19107223
TI  - The diagnosis of Cushing's syndrome: an endocrine society clinical practice
      guideline.

PMID- 19107224
TI  - National Academy of Clinical Biochemistry (NACB) laboratory medicine guidelines
      on the clinical utilization and analytical issues for cardiac biomarker testing
      in heart failure.

PMID- 19107225
TI  - Royal College of Pathologists of Australasia (RCPA) and Australasian Association
      of Clinical Biochemists (AACB) position statement on impaired fasting glucose.

PMID- 19107227
TI  - RET/PTC1-driven neoplastic transformation and proinvasive phenotype of human
      thyrocytes involve Met induction and beta-catenin nuclear translocation.
AB  - Activation of the RET gene by chromosomal rearrangements generating RET/PTC
      oncogenes is a frequent, early, and causative event in papillary thyroid
      carcinoma (PTC). We have previously shown that, in human primary thyrocytes,
      RET/PTC1 induces a transcriptional program including the MET proto-oncogene. In
      PTCs, beta-catenin is frequently mislocated to the cytoplasm nucleus. We
      investigated the interplay between Ret/ptc1 signaling and Met in regulating the
      proinvasive phenotype and beta-catenin localization in cellular models of human
      PTC. Here, we show that Met protein is expressed and is constitutively active in
      human thyrocytes exogenously expressing RET/PTC1 as well as a mutant (Y451F)
      devoid of the main Ret/ptc1 multidocking site. Both in transformed thyrocytes and
      in the human PTC cell line TPC-1, Ret/ptc1-Y451-dependent signaling and Met
      cooperated to promote a proinvasive phenotype. Accordingly, gene/functional
      silencing of either RET/PTC1 or MET abrogated early branching morphogenesis in
      TPC-1 cells. The same effect was obtained by blocking the common downstream
      effector Akt. Y451 of Ret/ptc1 was required to promote proliferation and nuclear
      translocation of beta-catenin, suggesting that these oncogene-driven effects are
      Met-independent. Pharmacologic inhibition of Ret/ptc1 and Met tyrosine kinases by
      the multitarget small molecule RPI-1 blocked cell proliferation and invasive
      ability and dislocated beta-catenin from the nucleus. Altogether, these results
      support that Ret/ptc1 cross talks with Met at transcriptional and signaling
      levels and promotes beta-catenin transcriptional activity to drive thyrocyte
      neoplastic transformation. Such molecular network, promoting disease initiation
      and acquisition of a proinvasive phenotype, highlights new options to design
      multitarget therapeutic strategies for PTCs.

PMID- 19107226
TI  - The story of human cytomegalovirus and cancer: increasing evidence and open
      questions.
AB  - Although human cytomegalovirus (HCMV) is generally not regarded to be an
      oncogenic virus, HCMV infection has been implicated in malignant diseases from
      different cancer entities. On the basis of our experimental findings, we
      developed the concept of "oncomodulation" to better explain the role of HCMV in
      cancer. Oncomodulation means that HCMV infects tumor cells and increases their
      malignancy. By this concept, HCMV was proposed to be a therapeutic target in a
      fraction of cancer patients. However, the clinical relevance of HCMV-induced
      oncomodulation remains to be clarified. One central question that has to be
      definitively answered is if HCMV establishes persistent virus replication in
      tumor cells or not. In our eyes, recent clinical findings from different groups
      in glioblastoma patients and especially the detection of a correlation between
      the numbers of HCMV-infected glioblastoma cells and tumor stage (malignancy)
      strongly increase the evidence that HCMV may exert oncomodulatory effects. Here,
      we summarize the currently available knowledge about the molecular mechanisms
      that may contribute to oncomodulation by HCMV as well as the clinical findings
      that suggest that a fraction of tumors from different entities is indeed infected
      with HCMV.

PMID- 19107228
TI  - Blocking of p53-Snail binding, promoted by oncogenic K-Ras, recovers p53
      expression and function.
AB  - Differentially from other kinds of Ras, oncogenic K-Ras, which is mutated
      approximately 30% of human cancer, does not induce apoptosis and senescence.
      Here, we provide the evidence that oncogenic K-Ras abrogates p53 function and
      expression through induction of Ataxia telangiectasia-mutated and Rad3-related
      mediated Snail stabilization. Snail directly binds to DNA binding domain of p53
      and diminishes the tumor-suppressive function of p53. Thus, elimination of Snail
      through si-RNA can induce p53 in K-Ras-mutated cells, whereas Snail and mutant K
      Ras can suppress p53 in regardless of K-Ras status. Chemicals, isolated from
      inhibitor screening of p53-Snail binding, can block the Snail-mediated p53
      suppression and enhance the expression of p53 as well as the transcriptional
      activity of p53 in an oncogenic K-Ras-dependent manner. Among the chemicals, two
      are very similar in structure. These results can answer why K-Ras can coexist
      with wild type p53 and propose the Snail-p53 binding as the new therapeutic
      target for K-Ras-mutated cancers including pancreatic, lung, and colon cancers.

PMID- 19107229
TI  - Blockade of Notch signaling in tumor-bearing mice may lead to tumor regression,
      progression, or metastasis, depending on tumor cell types.
AB  - It has been reported that blocking Notch signaling in tumor-bearing mice results
      in abortive angiogenesis and tumor regression. However, given that Notch
      signaling influences numerous cellular processes in vivo, a comprehensive
      evaluation of the effect of Notch inactivation on tumor growth would be
      favorable. In this study, we inoculated four cancer cell lines in mice with the
      conditional inactivation of recombination signal-binding protein-Jkappa (RBP-J),
      which mediates signaling from all four mammalian Notch receptors. We found that
      whereas three tumors including hepatocarcinoma, lung cancer, and osteogenic
      sarcoma grew slower in the RBP-J-deficient mice, at least a melanoma, B16, grew
      significantly faster in the RBP-J-deficient mice than in the controls, suggesting
      that the RBP-J-deficient hosts could provide permissive cues for tumor growth.
      All these tumors showed increased microvessels and up-regulated hypoxia-inducible
      factor 1alpha, suggesting that whereas defective angiogenesis resulted in
      hypoxia, different tumors might grow differentially in the RBP-J-deleted mice.
      Similarly, increased infiltration of Gr1(+)/Mac1(+) cells were noticed in tumors
      grown in the RBP-J-inactivated mice. Moreover, we found that when inoculated in
      the RBP-J knockout hosts, the H22 hepatoma cells had a high frequency of
      metastasis and lethality, suggesting that at least for H22, deficiency of
      environmental Notch signaling favored tumor metastasis. Our findings suggested
      that the general blockade of Notch signaling in tumor-bearing mice could lead to
      defective angiogenesis in tumors, but depending on tumor cell types, general
      inhibition of Notch signaling might result in tumor regression, progression, or
      metastasis.

PMID- 19107230
TI  - A quantitative volumetric micro-computed tomography method to analyze lung tumors
      in genetically engineered mouse models.
AB  - Two genetically engineered, conditional mouse models of lung tumor formation, K
      ras(LSL-G12D) and K-ras(LSL-G12D)/p53(LSL-R270H), are commonly used to model
      human lung cancer. Developed by Tyler Jacks and colleagues, these models have
      been invaluable to study in vivo lung cancer initiation and progression in a
      genetically and physiologically relevant context. However, heterogeneity,
      multiplicity and complexity of tumor formation in these models make it
      challenging to monitor tumor growth in vivo and have limited the application of
      these models in oncology drug discovery. Here, we describe a novel analytical
      method to quantitatively measure total lung tumor burden in live animals using
      micro-computed tomography imaging. Applying this methodology, we studied the
      kinetics of tumor development and response to targeted therapy in vivo in K-ras
      and K-ras/p53 mice. Consistent with previous reports, lung tumors in both models
      developed in a time- and dose (Cre recombinase)-dependent manner. Furthermore,
      the compound K-ras(LSL-G12D)/p53(LSL-R270H) mice developed tumors faster and more
      robustly than mice harboring a single K-ras(LSL-G12D) oncogene, as expected.
      Erlotinib, a small molecule inhibitor of the epidermal growth factor receptor,
      significantly inhibited tumor growth in K-ras(LSL-G12D)/p53(LSL-R270H) mice.
      These results demonstrate that this novel imaging technique can be used to
      monitor both tumor progression and response to treatment and therefore supports a
      broader application of these genetically engineered mouse models in oncology drug
      discovery and development.

PMID- 19107231
TI  - Evaluation of angiogenesis using micro-computed tomography in a xenograft mouse
      model of lung cancer.
AB  - Quantitative evaluation of lung tumor angiogenesis using immunohistochemical
      techniques has been limited by difficulties in generating reproducible data. To
      analyze intrapulmonary tumor angiogenesis, we used high-resolution micro-computed
      tomography (micro-CT) of lung tumors of mice inoculated with mouse Lewis lung
      carcinoma (LLC1) or human adenocarcinoma (A549) cell lines. The lung vasculature
      was filled with the radiopaque silicone rubber, Microfil, through the jugular
      vein (in vivo application) or pulmonary artery (ex vivo application). In
      addition, human adenocarcinoma lung tumor-bearing mice treated site-specifically
      with humanized monoclonal antibody (bevacizumab) against vascular endothelial
      growth factor. Quantitative analysis of lung tumor microvessels imaged with micro
      CT showed that more vessels (mainly small, <0.02 mm(2)) were filled using the in
      vivo (5.4%) compared with the ex vivo (2.1%) method. Furthermore, bevacizumab
      treated lung tumor-bearing mice showed significantly reduced lung tumor volume
      and lung tumor angiogenesis compared with untreated mice as assessed by micro-CT.
      Interestingly, microvascularization of mainly the smaller vessels (<0.02 mm(2))
      was reduced after bevacizumab treatment. This observation with micro-CT was
      nicely correlated with immunohistochemical measurement of microvessels.
      Therefore, micro-CT is a novel method for investigating lung tumor angiogenesis,
      and this might be considered as an additional complementary tool for precise
      quantification of angiogenesis.

PMID- 19107232
TI  - Oncogenic activation of MAP kinase by BRAF pseudogene in thyroid tumors.
AB  - Activating BRAF mutations have been reported in 40% of papillary thyroid
      carcinomas (PTCs). The involvement of BRAF pseudogene in thyroid tumorigenesis
      has not previously been studied. We investigated BRAF pseudogene expression in 68
      thyroid tumors: 16 multinodular goiters, 43 classic PTCs, 6 follicular variants
      of PTC, and 3 anaplastic thyroid carcinomas. BRAF pseudogene function was studied
      by Western blots, soft agar assay, and tumorigenesis in nude mice. BRAF
      pseudogene expression was detected in 7 multinodular goiters, 18 classic PTC, and
      1 follicular variants of PTC. There is an inverse correlation between BRAF
      pseudogene expression and BRAF mutation. The pseudogene transcripts were more
      frequently detected in tumors without BRAF mutation than those with BRAF
      mutation. Furthermore, BRAF pseudogene expression could activate the MAP kinase
      signaling pathway, transform NIH3T3 cells in vitro, and induce tumors in nude
      mice. These data suggest that BRAF pseudogene activation may play a role in
      thyroid tumor development.

PMID- 19107233
TI  - Cdc6 and cyclin E2 are PTEN-regulated genes associated with human prostate cancer
      metastasis.
AB  - Phosphatase and tensin homolog deleted on chromosome 10 (PTEN) is frequently
      inactivated in metastatic prostate cancer, yet the molecular consequences of this
      and their association with the metastatic phenotype are incompletely understood.
      We performed transcriptomic analysis and identified genes altered by conditional
      PTEN reexpression in C4-2, a human metastatic prostate cancer cell line with
      inactive PTEN. PTEN-regulated genes were disproportionately represented among
      genes altered in human prostate cancer progression and metastasis but not among
      those associated with tumorigenesis. From the former set, we identified two novel
      putative PTEN targets, cdc6 and cyclin E2, which were overexpressed in metastatic
      human prostate cancer and up-regulated as a function of PTEN depletion in poorly
      metastatic DU145 human prostate cancer cells harboring a wild type PTEN.
      Inhibition of cdc6 and cyclin E2 levels as a consequence of PTEN expression was
      associated with cell cycle G(1) arrest, whereas use of PTEN activity mutants
      revealed that regulation of these genes was dependent on PTEN lipid phosphatase
      activity. Computational and promoter-reporter evaluations implicated the E2F
      transcription factor in PTEN regulation of cdc6 and cyclin E2 expression. Our
      results suggest a hypothetical model whereby PTEN loss upregulates cell cycle
      genes such as cdc6 and cyclin E2 that in turn promote metastatic colonization at
      distant sites.

PMID- 19107234
TI  - Glioblastoma inhibition by cell surface immunoglobulin protein EWI-2, in vitro
      and in vivo.
AB  - EWI-2, a cell surface IgSF protein, is highly expressed in normal human brain but
      is considerably diminished in glioblastoma tumors and cell lines. Moreover, loss
      of EWI-2 expression correlated with a shorter survival time in human glioma
      patients, suggesting that EWI-2 might be a natural inhibitor of glioblastoma. In
      support of this idea, EWI-2 expression significantly impaired both ectopic and
      orthotopic tumor growth in nude mice in vivo. In vitro assays provided clues
      regarding EWI-2 functions. Expression of EWI-2 in T98G and/or U87-MG malignant
      glioblastoma cell lines failed to alter two-dimensional cell proliferation but
      inhibited glioblastoma colony formation in soft agar and caused diminished cell
      motility and invasion. At the biochemical level, EWI-2 markedly affects the
      organization of four molecules (tetraspanin proteins CD9 and CD81 and matrix
      metalloproteinases MMP-2 and MT1-MMP), which play key roles in the biology of
      astrocytes and gliomas. EWI-2 causes CD9 and CD81 to become more associated with
      each other, whereas CD81 and other tetraspanins become less associated with MMP-2
      and MT1-MMP. We propose that EWI-2 inhibition of glioblastoma growth in vivo is
      at least partly explained by the capability of EWI-2 to inhibit growth and/or
      invasion in vitro. Underlying these functional effects, EWI-2 causes a
      substantial molecular reorganization of multiple molecules (CD81, CD9, MMP-2, and
      MT1-MMP) known to affect proliferation and/or invasion of astrocytes and/or
      glioblastomas.

PMID- 19107237
TI  - It's all about the members.

PMID- 19107235
TI  - JC virus T-antigen in colorectal cancer is associated with p53 expression and
      chromosomal instability, independent of CpG island methylator phenotype.
AB  - JC virus has a transforming gene encoding JC virus T-antigen (JCVT). JCVT may
      inactivate wild-type p53, cause chromosomal instability (CIN), and stabilize beta
      catenin. A link between JCVT and CpG island methylator phenotype (CIMP) has been
      suggested. However, no large-scale study has examined the relations of JCVT with
      molecular alterations, clinical outcome, or prognosis in colon cancer. We
      detected JCVT expression (by immunohistochemistry) in 271 (35%) of 766 colorectal
      cancers. We quantified DNA methylation in eight CIMP-specific promoters (CACNA1G,
      CDKN2A, CRABP1, IGF2, MLH1, NEUROG1, RUNX3, and SOCS1) and eight other loci
      (CHFR, HIC1, IGFBP3, MGMT, MINT1, MINT31, p14, WRN) by MethyLight. We examined
      loss of heterozygosity in 2p, 5q, 17q, and 18q. JCVT was significantly associated
      with p53 expression (P < .0001), p21 loss (P < .0001), CIN (>/=2 chromosomal
      segments with LOH; P < .0001), nuclear beta-catenin (P = .006), LINE-1
      hypomethylation (P = .002), and inversely with CIMP-high (P = .0005) and
      microsatellite instability (MSI) (P < .0001), but not with PIK3CA mutation. In
      multivariate logistic regression analysis, the associations of JCVT with p53
      [adjusted odds ratio (OR), 8.45; P < .0001], CIN (adjusted OR, 2.53; P = .003),
      cyclin D1 (adjusted OR, 1.57; P = .02), LINE-1 hypomethylation (adjusted OR, 1.97
      for a 30% decline as a unit; P = .03), BRAF mutation (adjusted OR, 2.20; P =
      .04), and family history of colorectal cancer (adjusted OR, 0.64; P = .04)
      remained statistically significant. However, JCVT was no longer significantly
      associated with CIMP, MSI, beta-catenin, or cyclooxygenase-2 expression in
      multivariate analysis. JCVT was unrelated with patient survival. In conclusion,
      JCVT expression in colorectal cancer is independently associated with p53
      expression and CIN, which may lead to uncontrolled cell proliferation.

PMID- 19107236
TI  - Hedgehog pathway inhibitor HhAntag691 is a potent inhibitor of ABCG2/BCRP and
      ABCB1/Pgp.
AB  - HhAntag691 (GDC-0449), a low-molecular weight inhibitor of the tumor-promoting
      hedgehog (Hh) signaling pathway, has been used to treat medulloblastoma in animal
      models and has recently entered clinical trials for a variety of solid tumors.
      Here, we show that HhAntag691 inhibits multiple ATP-binding cassette (ABC)
      transporters. ATP-binding cassette transporters are within a family of membrane
      proteins, the overexpression of which is associated with multidrug resistance, a
      major impediment to successful cancer treatment. HhAntag691 is a potent inhibitor
      of two ABC transporters, ABCG2/BCRP and ABCB1/Pgp, and is a mild inhibitor of
      ABCC1/MRP1. In ABCG2-overexpressing HEK293 cells, HhAntag691 increased retention
      of the fluorescent ABCG2 substrate BODIPY-prazosin and resensitized these cells
      to mitoxantrone, an antineoplastic ABCG2 substrate. In Madin-Darby canine kidney
      II cells engineered to overexpress Pgp or MRP1, HhAntag691 increased the
      retention of calcein-AM and resensitized them to colchicine. HhAntag691 also
      resensitized human non-small cell lung carcinoma cells NCI-H460/par and NCI
      H460/MX20, which overexpress ABCG2 in response to mitoxantrone, to mitoxantrone,
      and to topotecan or SN-38. The IC(50) values of HhAntag691 for inhibition of
      ABCG2 and Pgp were approximately 1.4 and approximately 3.0 microM, respectively.
      Because ABC transporters are highly expressed at the blood-brain barrier and on
      many tumor cells, they contribute significantly to treatment failure of many
      types of cancer, particularly of those within the neuraxis. In addition to its
      effect on Hh signaling, the ability of HhAntag691 and related compounds to
      inhibit two key ABC transporters could contribute to their effectiveness in
      treating malignancies.

PMID- 19107238
TI  - Workplace asthma.

PMID- 19107240
TI  - Direct costs of occupational asthma in Quebec between 1988 and 2002.
AB  - BACKGROUND: Forty to 70 cases of occupational asthma due to sensitization to an
      agent present in the workplace are accepted each year by the Commission de la
      sante et de la securite du travail, the Quebec medicolegal agency. OBJECTIVES AND
      METHODS: In a random sample of eight to 10 accepted claims per year from 1988 to
      2002, the direct costs of compensation for loss of income (CLI) and compensation
      for functional impairment (CFI), as well as the associations of these costs with
      selected variables, were assessed. RESULTS: Mean costs (presented as Canadian
      dollars x10(3)) of CLI, CFI and total were 72.5, 11.7 and 92.8, respectively,
      while the median costs were 40.7, 7.6 and 61.3 for CLI, CFI and total,
      respectively. Median CLI costs were significantly higher in men than women (69.9
      versus 13.1), workers aged 40 years or older versus those younger than 40 years
      (90.1 versus 27.4), workers with occupational asthma due to workplace exposure to
      low versus high molecular weight agents (51.2 versus 38.6), and workers taking
      inhaled steroids at diagnosis (92 versus 52) and reassessment (81 versus 35).
      Median CFI costs were also higher in those requiring retraining (10.4) and taking
      early retirement (61.8) than workers who stayed with the same employer but in a
      different job (5.4). Median CFI costs were significantly higher for individuals
      being treated with inhaled steroids at the time of diagnosis (14.0 versus 5.2)
      and reassessment (13 versus 6), and for those left with bronchial
      hyperresponsiveness (9.5 versus 0.8) related to forced expiratory volume in 1 s
      and forced expiratory volume in 1 s/forced vital capacity. CONCLUSION: Age, sex,
      nature of occupational agent, treatment with inhaled steroids and type of
      rehabilitation all affect CLI, whereas lung function status at baseline and
      reassessment is related to CFI.

PMID- 19107239
TI  - Work-related asthma in Montreal, Quebec: population attributable risk in a
      community-based study.
AB  - BACKGROUND: Occupational exposures are an important cause of adult-onset asthma
      but the population attributable risk percentage (PAR%) has been less frequently
      studied. OBJECTIVES: To examine the distribution and determinants of adult asthma
      in six centres across Canada using data gathered in a community-based study.
      METHODS: Data were gathered in a community survey of 2959 adults using the
      European Community Respiratory Health Survey Protocol. A subsample of 498
      subjects completed detailed health and occupational questionnaires, methacholine
      challenge tests and allergy skin tests. Asthma was defined in three ways: current
      wheeze, asthma symptoms and/or medication, and airway hyperresponsiveness.
      Occupational exposures were classified as sensitizers or irritants. Associations
      between asthma and occupational exposures were examined using logistic regression
      analysis. Model selection was based on the findings for current wheeze, and the
      same model was applied to the other definitions of asthma. RESULTS: Fifty-six per
      cent of subjects reported ever having had occupational exposure to sensitizers,
      and 9.8% to irritants. Current wheeze was associated with exposure to irritants
      (PAR% 4.54%), and airway hyperresponsiveness was associated with exposure to
      sensitizers (PAR% 30.7%). Neither a history of childhood asthma, atopy, nor
      confining the analysis to adult-onset asthma affected these associations.
      Analysis of effect modification suggested two types of work-related asthma: one
      due to exposure to occupational sensitizers, and the other due to exposure to
      irritants. CONCLUSIONS: Detailed assessment of past and current exposures is
      essential in the investigation of work-related asthma. Childhood asthma
      reactivated or aggravated by work exposures is not easy to distinguish from
      asthma induced by work, a misclassification that could lead to an underestimation
      of work-induced asthma. This should be taken into account in jurisdictions in
      which persons with work-aggravated asthma are not eligible for workers'
      compensation.

PMID- 19107241
TI  - The sex factor: epidemiology and management of chronic obstructive pulmonary
      disease in British Columbia.
AB  - BACKGROUND: The prevalence and mortality of chronic obstructive pulmonary disease
      (COPD) in women have been predicted to overtake that of men within the next
      decade. These predictions are based in part on data from surveys using self
      reports of a COPD diagnosis. Whether these predictions have been realized is
      unknown. METHODS: The prevalence and mortality of men and women in British
      Columbia were compared from fiscal years 1992/1993 to 2003/2004 using
      administrative health services data. Case definitions for COPD were developed
      using International Classification of Diseases ninth and 10th revision (ICD-9/10)
      codes applied to medical and hospital data. Individuals 45 years and older, who
      had at least two physician visits or one hospitalization for specified COPD ICD
      9/10 codes within a 365-day window, were considered to be cases. Cases were
      ascertained from 1992 to 2004. RESULTS: In 2003/2004, men had a greater
      prevalence (4.7% versus 4.0% in women) and a higher all-cause mortality rate
      (5.4% versus 4.1% in women) than women. Both men and women with COPD had low COPD
      medication use (45%) and low referral for lung function testing (55%). Including
      the ICD-9 code for 'bronchitis, not specified as acute or chronic' (ICD-9 490) in
      the case definition resulted in a greater prevalence of COPD in women than in men
      overall, and in the 45 to 64 year age group. CONCLUSION: Prevalence and mortality
      measured with administrative health data do not show evidence of relative
      increase in the prevalence of COPD for women in British Columbia. However,
      further analysis of ICD-9 490 may identify an early 'at-risk' group, specifically
      in women.

PMID- 19107242
TI  - Asthma control score based on filled medication prescriptions: a validation
      study.
AB  - BACKGROUND: Periodic measurement of disease control is recommended to
      characterize asthma and monitor treatment. OBJECTIVE: To elaborate and validate
      an asthma control score (ACS) for use in studies based on administrative health
      databases. METHODS: Adult patients with asthma were recruited from a clinic. The
      ACS is based on the average number of doses of short-acting inhaled beta(2)
      agonists taken per week and short courses of oral corticosteroids dispensed over
      a three-month period. Data were obtained from the Regie de l'assurance maladie du
      Quebec database in Canada. The ACS was compared with the asthma control
      questionnaire and the use of health care services for asthma over a 12-month
      period. RESULTS: A total of 60 patients were enrolled. They had a mean (+/- SD)
      age of 50.4+/-13.9 years, and 43.3% were male. Patients had had asthma for 20.8+/
      15.1 years on average and had a mean prebronchodilator forced expiratory volume
      in 1 s of 77.0% of the predicted value. The mean ACS was 8.3+/-11.6, with a range
      of 0 to 60. The ACS was not found to be correlated with the asthma control
      questionnaire, but it was significantly associated with health care services
      used. For each additional point in the ACS, patients were 2% more likely to need
      acute care for asthma (rate ratio 1.02; P=0.02). CONCLUSIONS: Further studies
      including patients followed by general practitioners are required before the
      general use of this score. This innovative score is useful to rapidly assess the
      control of asthma over long periods of time and at a low cost in studies using
      administrative drug databases.

PMID- 19107243
TI  - Addition of sildenafil in patients with pulmonary arterial hypertension with
      inadequate response to bosentan monotherapy.
AB  - BACKGROUND: Pulmonary arterial hypertension (PAH) remains a progressive disease
      despite improvement when using one of three medication classes: prostanoids,
      endothelin receptor antagonists or phosphodiesterase-5 inhibitors. Combination
      therapy has been proposed for patients with unsatisfactory response to
      monotherapy. OBJECTIVES: To examine the effect of adding sildenafil to bosentan
      on 6 min walk distance (6MWD) and New York Heart Association (NYHA)
      classification in patients with PAH who achieved inadequate improvement with
      bosentan monotherapy. METHODS: Patients with idiopathic PAH or connective tissue
      disease-associated PAH, and who had either self-reported inadequate improvement
      in exercise tolerance or a decline in 6MWD after initial improvement, were
      included in the study (n=10). Data on 6MWD and NYHA class at baseline (before
      initiation of bosentan), three and six months after baseline, second baseline
      (before initiation of combination therapy with sildenafil), and three and six
      months after second baseline were analyzed for any changes. RESULTS: Mean time
      from initiation of bosentan monotherapy to initiation of combination therapy was
      558 days (range 150 to 900 days). Six months after initiation of bosentan, 6MWD
      increased by 57.2 m above the baseline of 314.4 m. Six months after combination
      therapy, 6MWD was 62.80 m higher than the baseline before initiation of
      combination therapy of 339 m (P<0.02). The overall increase in 6MWD six months
      after combination therapy was higher than the first baseline by 87.4 m (P not
      significant). NYHA functional class did not improve with combination therapy in
      all patients. DISCUSSION: Initiating combination therapy in patients who achieve
      an inadequate improvement in exercise tolerance with monotherapy may result in
      further improvement in exercise tolerance.

PMID- 19107244
TI  - Quality of bronchial biopsies for morphology study and cell sampling: a
      comparison of asthmatic and healthy subjects.
AB  - BACKGROUND: Bronchial biopsies are widely used for histopathological, primary
      cell culture and genetic studies, but very few reports have evaluated their
      quality. OBJECTIVES AND METHODS: The present project evaluated the quality (using
      a scoring system) and the general morphology of a pool of six bronchial biopsy
      specimens taken from three different sampling sites (the lobar, segmental and
      subsegmental carinae) in 27 subjects (13 asthmatic subjects and 14 healthy
      controls). The present study also assessed quantitative measurements of
      structural changes related to asthma. RESULTS: In total, 94.4% of the biopsy
      attempts had enough tissue to be processed. From these, 61.7% were scored with a
      good to excellent quality, while 76.5% presented smooth muscle bundles and 40.5%
      had an intact epithelium wall. The data also confirmed the structural changes
      observed in asthma, such as increased apparent thickening of the basement
      membrane, reduced amounts of smooth muscle for healthy controls and decreased
      percentage of intact epithelium for asthmatic subjects. CONCLUSION: A pool of six
      bronchial biopsy specimens can provide tissue of excellent quality in both
      asthmatic and healthy subjects and, consequently, a valuable sample for
      morphological analysis of mucosal structures.

PMID- 19107246
TI  - Chemoradiation-induced superior vena cava syndrome: a case report.
AB  - A case of a 54-year-old man who developed superior vena cava syndrome secondary
      to vascular fibrosis, 30 months after radical chemoradiation for stage III non
      small cell lung cancer, is presented. The literature regarding the etiology,
      diagnosis and treatment of this rare entity is discussed.

PMID- 19107245
TI  - Cost-effectiveness of combination therapy for chronic obstructive pulmonary
      disease.
AB  - BACKGROUND: There is evidence that combination therapy (CT) in the form of long
      acting beta(2)-agonists (LABAs) and inhaled corticosteroids can improve lung
      function for patients with chronic obstructive pulmonary disease (COPD).
      OBJECTIVE: To determine the cost-effectiveness of using CT in none, all or a
      selected group of COPD patients. METHODS: A Markov model was designed to compare
      four treatment strategies: no use of CT regardless of COPD severity (patients
      receive LABA only); use of CT in patients with stage 3 disease only (forced
      expiratory volume in 1 s [FEV(1)] less than 35% of predicted); use of CT in
      patients with stages 2 and 3 disease only (FEV(1) less than 50% of predicted);
      and use of CT in all patients regardless of severity of COPD. Estimates of
      mortality, exacerbation and disease progression rates, quality- adjusted life
      years (QALYs) and costs were derived from the literature. Three-year and lifetime
      time horizons were used. The analysis was conducted from a health systems
      perspective. RESULTS: CT was associated with a cost of $39,000 per QALY if given
      to patients with stage 3 disease, $47,500 per QALY if given to patients with
      stages 2 and 3 disease, and $450,333 per QALY if given to all COPD patients.
      Results were robust to various assumptions tested in a Monte Carlo simulation.
      CONCLUSION: Providing CT for COPD patients in stage 2 or 3 disease is cost
      effective. The message to family physicians and specialists is that as FEV(1)
      worsens and reaches 50% of predicted values, CT is recommended.

PMID- 19107247
TI  - Effect of reduced post length on the resistance to fracture of crowned,
      endodontically treated teeth.
AB  - OBJECTIVE: To examine the influence of a reduced post length sealed with a
      titanium-reinforced composite luting agent on the fracture resistance of crowned
      endodontically treated teeth with a 2-mm ferrule on healthy tooth structure.
      METHOD AND MATERIALS: The study consisted of 60 intact single-rooted premolars
      with similar root diameters and lengths. Teeth were endodontically treated and
      randomly divided into 6 experimental groups (n = 10) with various post lengths
      (5, 8, and 10 mm) and types (ParaPost and Dentatus) of equal diameter. Posts were
      luted with a titanium-reinforced composite resin luting agent. Titanium
      reinforced composite resin cores were constructed, and cast crowns with a 2-mm
      ferrule on healthy tooth structure were cemented. Specimens were mounted in a jig
      that allowed loading of the buccal cusp in the axio-occlusal line at a 30-degree
      angle to the long tooth axis. A continuous compressive force at a crosshead speed
      of 2 mm/min was applied by an Instron testing machine. Forces at fracture (in
      newtons) and mode of failure were recorded. One-way analysis of variance (ANOVA)
      and the Scheffe test were used to statistically compare the differences among
      groups at a significance of 5%. RESULTS: ANOVA showed no statistically
      significant differences among the mean failure forces for the tested groups in
      their resistance to fracture under load. The Scheffe contrast test showed no
      statistically significant differences among all combinations of the 6 tested
      groups (F [5.59] = 0.032; P > .05). CONCLUSION: Within the limitations of this
      study, post length did not influence the fracture resistance of crowned
      endodontically treated teeth with a 2-mm ferrule on healthy tooth structure. For
      tooth resistance, prosthesis design is more important than post characteristics.

PMID- 19107248
TI  - Effect of remaining coronal structure on the resistance to fracture of crowned
      endodontically treated maxillary first premolars.
AB  - OBJECTIVE: Endodontically treated maxillary first premolars present a restorative
      challenge. The objective of the present study was to assess the resistance to
      fracture of crowned endodontically treated maxillary first premolars under
      simulated occlusal load, while preserving various degrees of remaining coronal
      structure. METHODS AND MATERIALS: The study consisted of 50 intact maxillary
      first premolars with bifurcated roots and similar root diameter and length,
      randomly divided into 5 equal experimental groups. All dowels were luted with
      Flexi-Flow titanium-reinforced composite resin cement. TiCore titanium-reinforced
      composite resin was used to fabricate the core. Complete cast crowns were
      fabricated and cemented with zinc phosphate cement. Forces at fracture and mode
      of failure were recorded. RESULTS: Statistically significant differences (P <
      .05) were found among mean failure forces for all tested groups in their
      resistance to fracture under load with the Kruskal-Wallias test and among all
      combinations of the 5 groups (Z = -1.56/-2.34; P > .05) with the Mann-Whitney
      test. This indicates that crowned maxillary first premolars with varying degrees
      of remaining coronal structure differ significantly in their resistance to
      fracture under occlusal load. There was increased protection against fracture
      under occlusal loads with more remaining tooth structure. CONCLUSIONS: Within the
      limitations of this study, remaining coronal structure influenced the fracture
      resistance of crowned endodontically treated maxillary first premolars.
      Preservation of tooth structure is important for its protection against fracture
      under occlusal loads and may influence the tooth prognosis.

PMID- 19107249
TI  - The dentist in society part 4: a ticket for every season.

PMID- 19107250
TI  - Optical integration of incisoproximal restorations using the natural layering
      concept.
AB  - OBJECTIVE: To evaluate the optical integration of 4 contemporary composite resin
      materials used for incisoproximal restorations and the natural layering concept.
      METHOD AND MATERIALS: Miris 2 (M2; Coltene Whaledent), Gradia Direct (GD; GC),
      Enamel Plus HFO (HFO; Micerium), and Filtek Supreme Plus (FSP; 3M ESPE) composite
      resins were used to consecutively restore 6 extracted incisors with
      incisoproximal restorations using the natural layering concept, mimicking the
      natural anatomy of the tooth with only 2 composite resin masses (dentin and
      enamel). Following each restoration, the specimen was allowed to rehydrate for 2
      weeks and was then photographed under standardized conditions (direct, indirect,
      and fluorescent lights). Six independent evaluators scored each light condition
      using an optical integration score on a scale from 1 to 4 (1 = worst optical
      integration, restoration can be easily distinguished from remaining tissues; 4 =
      optimal optical integration, restoration "invisible"). Mean optical integration
      scores (from the 6 evaluators) were analyzed with a 2-way analysis of variance
      (ANOVA) (composite resin brand and light condition). Pooled data of M2 and HFO
      (single-hue systems) and GD and FSP (multiple-hue systems) were also analyzed
      with a 2-way ANOVA (shade system and light condition). RESULTS: M2 obtained the
      highest optical integration scores (P < .03), followed by GD and HFO (not
      significantly different, P = .99). FSP showed the least favorable optical
      behavior (P < .0001), which is explained in part by the lack of fluorescence and
      possible inappropriateness for use with the natural layering technique. Single
      hue systems (M2 and HFO) achieved better optical integration (P < .02) compared
      to multihue systems (GD and FSP). CONCLUSIONS: For M2, the simplified natural
      layering concept produced incisoproximal restorations with excellent optical
      integration. GD and HFO are also suitable for this technique. FSP failed to
      produce acceptable optical integration in the present study.

PMID- 19107252
TI  - Use of panoramic radiography to predict possible maxillary sinus membrane
      perforation during dental extraction.
AB  - OBJECTIVE: To determine if the use of panoramic radiographs is a reliable method
      of predicting maxillary sinus membrane exposure or perforation during extraction
      of maxillary teeth. METHOD AND MATERIALS: The radiographs of 72 patients were
      evaluated before extraction of maxillary teeth, and a prediction was made whether
      exposure or perforation of the sinus membrane was likely. This decision was based
      on the proximity of the root tip to the radiographic floor of the maxillary
      sinus. The extraction site was then evaluated to determine if the sinus membrane
      was visible or if a perforation had occurred. RESULTS: Possible exposure or
      perforation of the maxillary sinus was predicted in 27 patients. In this subset
      of patients, it actually occurred 4 times (14.8%). However, it also occurred 5
      times when not predicted (11.0%). CONCLUSION: Use of panoramic radiographs is not
      a reliable method to predict the likelihood of sinus involvement following the
      extraction of posterior maxillary teeth.

PMID- 19107251
TI  - Vital tooth bleaching: biologic adverse effects-a review.
AB  - Depending on etiology, the esthetic treatment of dyschromia may involve vital
      tooth- bleaching techniques. Hydrogen peroxide is the active molecule used for
      such procedures; however, its action mechanism is not clearly understood.
      Moreover, a variety of contradictory studies make difficult the evaluation of the
      safety of bleaching techniques. The purpose of this article is therefore to
      review the available literature (1) to describe the physicochemical properties of
      hydrogen peroxide and (2) to assess the safety of its use as a vital tooth
      bleaching agent. Indeed, based on hydrogen peroxide's capacity to generate free
      radicals that diffuse throughout the dental hard tissues, concerns have been
      addressed regarding the adverse effects that bleaching products can induce on the
      enamel and dentin structures, pulp, and bonding to a composite resin system.
      Moreover, during self-application of home bleaching products, hydrogen peroxide
      is released into the oral cavity and ingested. Some questions have therefore
      arisen concerning its toxicity and its possible carcinogenicity.

PMID- 19107253
TI  - A retrospective case series of implants used to restore partially edentulous
      patients with implant-supported removable partial dentures: 31-month mean follow
      up results.
AB  - OBJECTIVE: The incorporation of dental implants into removable partial dentures
      is a common clinical practice, but it is poorly documented in the dental
      literature. The purpose of this retrospective case series study was to evaluate
      the survival of endosseous dental implants used in restoring partially edentulous
      patients with implant-supported removable partial dentures (ISRPDs) of different
      configurations, based on up to 10 years of follow-up. METHOD AND MATERIALS: The
      sample consisted of 23 consecutively treated partially edentulous patients, who,
      between 1996 and 2005, had a total of 44 implants placed in different arch sites
      and who were treated with ISRPDs. The mean age was 44.2 +/- 7.5 years at
      inclusion. Mean follow-up time from implant placement was 31.5 months (range, 9
      to 120 months). Smoking status, arch configuration before and after implant
      placement, follow-up time from implant placement, implant location, implant
      dimensions, implant and abutment survival, and overall satisfaction (assessed by
      questionnaire) with the restoration are presented. RESULTS: The overall implant
      survival rate was 95.5%; 2 implants failed. Kennedy Class I in the maxilla (6
      patients) followed by Kennedy Class II in the mandible (4 patients) were the most
      prevalent arch configurations before implant placement. Arch configuration was
      modified by implant placement in 6 patients (26.1%). During follow-up, 1 abutment
      tooth was lost 2 years after prosthesis delivery. All patients were satisfied
      with their prosthesis. CONCLUSIONS: Implant-supported removable partial dentures
      could serve as a long-term predictable treatment modality. Careful patient
      selection, with an appropriate maintenance and recall system, is recommended to
      obtain satisfactory results.

PMID- 19107254
TI  - Oral effects of nonmyeloablative stem cell transplantation: a prospective
      observational study.
AB  - OBJECTIVE: Nonmyeloablative stem cell transplantation (NST) is a relatively new
      type of hematopoietic stem cell transplantation (HSCT) that has gained wider use
      in the last decade. Oral effects of NST have not been described. The goal of the
      study was to evaluate the oral mucosal effects, including oral acute graft versus
      host disease (aGVHD), in patients undergoing NST in comparison to patients
      undergoing myeloablative HSCT. METHOD AND MATERIALS: This prospective,
      longitudinal pilot study included 34 consecutive patients undergoing HSCT.
      Demographic data were collected. Patients were evaluated every 2 weeks between
      baseline and day 100 posttransplantation. Statistical methods included univariate
      and multivariable regression analyses (level of significance, P < .05) . RESULTS:
      Patients undergoing NST had significantly less oral aGVHD (P = .032, OR = 0.11,
      CI: 0.02-0.83). Systemic aGVHD-related lesions were common in all patients. The
      prevalence of opportunistic oral infections was not statistically different
      between the NST and ablative groups (P = .94). CONCLUSIONS: In this pilot study,
      cancer patients treated with NST had a lower incidence of oral aGVHD than those
      receiving myeloablative HSCT. The incidence of other oral soft tissue lesions,
      including opportunistic infections, was not affected by the type of HSCT.

PMID- 19107255
TI  - Aneurysmal bone cyst of the tuberculum articulare of the temporomandibular joint:
      a case report.
AB  - A case is presented of a 14-year-old boy with aneurysmal bone cyst of the
      tuberculum articulare of the temporomandibular joint (TMJ). This disease rarely
      involves the skull, and involvement of temporal bone is even more rare. To our
      knowledge, only 22 cases have been reported in the literature. This is the first
      case of aneurysmal bone cyst of the tuberculum articulare of the TMJ described in
      the literature.

PMID- 19107256
TI  - Influence of cracks on leakage and obturation efficiency of root-end filling
      materials after ultrasonic preparation: an in vitro evaluation.
AB  - OBJECTIVES: To evaluate (1) the apical seal of root-end cavities using mineral
      trioxide aggregate (MTA) and glass-ionomer cement in teeth with and without
      cracks after ultrasonic root-end preparation and (2) the obturation efficiency of
      the materials in the root-end cavities. METHOD AND MATERIALS: Sixty teeth with
      root-end cavities were divided into 3 groups: teeth without cracks (-) (group A)
      and teeth with cracks (+) (group B). The third group (4 teeth) served as a
      control. Groups A and B were each divided into 2 subgroups: Groups 1A and 1B were
      filled with Fuji IX capsules (GC) after treatment with cavity conditioner; groups
      2A and 2B were filled with white MTA (Dentsply). The teeth were immersed in india
      ink and cleared. Apical leakage was measured from the resection surface to the
      maximal point of ink infiltration. Obturation efficiency was scored as good
      (acceptable), irregular (acceptable), or poor (unacceptable). Statistical
      analysis was performed using nonparametric and Fisher exact tests. RESULTS:
      Apical leakage could be arranged in the following order: Fuji IX+ > MTA+ > Fuji
      IX- > MTA-. Significant differences between Fuji IX- and Fuji IX+ (P < .001) and
      between MTA- and MTA+ (P < .001) were demonstrated. Fuji IX showed significantly
      more unacceptable fillings than did MTA (P < .005). No correlation between
      obturation efficiency and apical leakage was demonstrated (P > .05). CONCLUSION:
      The presence of cracks originating from the root canal negatively influences the
      seal of root-end filling materials and is probably of major clinical importance.
      MTA and Fuji IX showed equal sealing capacity, but MTA showed better obturation
      efficiency in the root-end cavity than Fuji IX.

PMID- 19107257
TI  - Adenomatoid odontogenic tumor developing in association with an odontoma: report
      of a case.
AB  - The adenomatoid odontogenic tumor is an unusual lesion that usually presents in
      the anterior maxilla. In contrast, the odontoma is the most common odontogenic
      tumor. The concurrent occurrence of these tumors in a single lesion is extremely
      rare. Such a lesion occurred in the mandibular canine region of a 13-year-old
      boy. While the hard tissue component of the lesion consisted of irregularly
      organized enamel and dentin matrix, the soft tissue component was composed of
      loosely arranged spindle cells and whorled masses of cells. Ductlike structures
      were observed around eosinophilic matrix. The histopathologic findings were
      consistent with concurrent occurrence of an odontoma and adenomatoid odontogenic
      tumor.

PMID- 19107258
TI  - Foreign body in the maxillary sinus: report of an unusual case.
AB  - The accidental displacement of foreign bodies into the maxillary sinus is not an
      unusual complication in dental clinical practice. However, dental materials, and,
      in particular, dental impression materials, introduced into the sinus several
      weeks to months after a maxillary tooth extraction or dentoalveolar surgery
      through either a small, long-standing oroantral fistula or an insufficiently
      healed extraction wound is uncommon. In the case reported, 3 months after a
      maxillary molar extraction, the material used for maxillary impression was pushed
      into the antrum through a small, almost invisible, oroantral fistula that was
      unseen by the specialists the patient had been visiting, worsening the patient's
      existing sinusitis.

PMID- 19107259
TI  - Radiographic diagnostics: Osteoma of the left mandibular notch.

PMID- 19107260
TI  - The Dentist in Society Part 3: setting priorities.

PMID- 19107261
TI  - The central single implant in the edentulous mandible: improvement of function
      and quality of life. A report of 2 cases.
AB  - Implant-retained overdentures are a reliable treatment option for edentulous
      patients, especially when only few implants can be placed. Internationally, 2
      implants are considered adequate to retain an overdenture in the edentulous
      mandible. However, for many patients, 2 implants can be cost-prohibitive. By
      means of 2 clinical cases, it is shown that the insertion of a single implant in
      the middle of the mandible might stabilize the prosthesis and improve the oral
      health quality of life and the chewing function. A ball attachment with a screw
      activated matrix was used to retain the overdenture. Early clinical results are
      promising. However, before this method can be recommended for general clinical
      application, long- term clinical results are needed.

PMID- 19107262
TI  - Evaluation of 2 endodontic techniques used to treat human primary molars with
      furcation radiolucency area: A 48-month radiographic study.
AB  - OBJECTIVE: To evaluate 2 techniques for the treatment of human primary molars
      with necrotic pulp and bifurcation bone loss by means of radiographic examination
      for 48 months. METHOD AND MATERIALS: Fifty-one mandibular primary molars were
      evaluated in children ranging from 4.5 to 6.5 years of age. The teeth with
      necrotic pulp and bifurcation bone loss were diagnosed by radiographic
      examination. The teeth were divided into 2 groups: group 1 (28 teeth) --
      pulpotomy technique using formocresol as a temporary dressing between sessions
      and coronal chamber obturation with zinc oxide-eugenol cement; and group 2 (23
      teeth) -- pulpectomy technique with calcium hydroxide paste as a temporary
      dressing between sessions and root canal obturation with a dense calcium
      hydroxide paste. Standardized radiographs were taken immediately after the
      fillings were completed and after 12, 24, 36, and 48 months. The radiographs were
      digitized and analyzed with software that outlined and measured the bifurcation
      radiolucency. RESULTS: Bifurcation radiolucency reduced significantly or repaired
      completely for both treatments in the first 12 months. Minor radiographic
      reduction of the lesion was observed from 12 to 24 months, and no significant
      reduction of the remaining radiolucent area was observed from 24 to 48 months
      after treatment. CONCLUSION: The 2 endodontic techniques evaluated showed similar
      results. The main effect of treatment on the lesion repair was obtained in the
      first year after treatment.

PMID- 19107263
TI  - Impact of clinical experience on the accuracy of probing depth measurements.
AB  - OBJECTIVE: To evaluate the influence of examiner experience on the variability of
      periodontal probing depth measurements obtained by conventional manual probing.
      METHOD AND MATERIALS: Thirty subjects with a diagnosis of chronic periodontitis
      were evaluated by an experienced examiner using an electronic probe and randomly
      assigned to 3 groups. Examiners with different levels of experience
      (undergraduate students, postgraduate students, and associate professors)
      evaluated each group with a manual probe. Electronic and conventional probing
      were repeated 45 days after cause-related periodontal therapy. RESULTS: A total
      of 8,127 periodontal sites were evaluated at the baseline examination and
      reassessment. Agreement between methods was satisfactory at the baseline
      examination (kappa = 0.45; P < .001) and reassessment (kappa = 0.42; P < .001).
      The best agreement between electronic and manual probing at the baseline
      examination was obtained by the postgraduate students (kappa = 0.66) and at
      reassessment by the associate professors (kappa = 0.60). Undergraduate students
      obtained the lowest agreement values in both examinations (kappa = 0.42 and 0.11,
      respectively). CONCLUSION: Examiner experience has direct influence on the
      accuracy of measurements. Dental schools must evaluate if the methodology
      employed to teach the use of conventional manual probing is effectively
      qualifying their students for dental practice.

PMID- 19107264
TI  - Bilateral twinned teeth and multiple supernumerary teeth: a case report.
AB  - Dental twinning can result from the fusion of the developing dental germinal
      elements or the gemination of a single germ. In bilateral anterior and posterior
      dental twinning, problems such as poor esthetics, dental caries, arch-length
      problems, and periodontal disease often occur as a result of the irregular
      morphology. Several treatment methods have been described in the literature with
      respect to the different types and morphologic variations of twinned teeth,
      including endodontic, restorative, surgical, periodontal, and orthodontic
      treatment. This report documents the case of a young patient with an exceedingly
      rare phenomenon of permanent twinned teeth and multiple supernumerary teeth in
      both sides of the mandibular and maxillary arches, as a result of combined fusion
      and gemination.

PMID- 19107265
TI  - Measurement of select physical and mechanical properties of 3 machinable ceramic
      materials.
AB  - OBJECTIVE: To measure select physical and mechanical properties of 3 machinable
      ceramic materials (IPS Empress CAD, Ivoclar Vivadent; Vitablocs Mark II, Vident;
      Paradigm C, 3M ESPE). METHOD AND MATERIALS: The physical and mechanical
      properties tested were hardness (using Vickers hardness), flexural strength and
      modulus (with 3-point bending), fracture toughness (with Vickers hardness
      indentation), and coefficient of thermal expansion (using a thermomechanical
      analyzer). For each of the materials, 25 specimens were fabricated to test each
      property, except for coefficient of thermal expansion, where n = 5. For each
      tested property, data were analyzed using 1-way analysis of variance and Tukey
      Studentized range test (significance level = .05), when required for post hoc
      testing. RESULTS: Mean Vickers hardness ranged from 511.3 (SD 8.6) for Paradigm C
      to 569.3 (SD 10.2) for Vitablocs Mark II. Flexural strength was greatest for IPS
      Empress CAD at 137.51 (SD 23.34) MPa and least for Vitablocs Mark II at 94.08 (SD
      14.21) MPa. Flexural modulus ranged from 8.65 (SD 2.24) GPa (Vitablocs Mark II)
      to 16.10 (SD 5.94) GPa (IPS Empress CAD). IPS Empress CAD had the highest
      fracture toughness at 2.18 (SD 0.30) MPa.m(1/2), while Vitablocs Mark II had the
      lowest at 1.37 (SD 0.22) MPa.m(1/2). Paradigm C exhibited the highest thermal
      expansion coefficient at 16.87 (SD 4.37) 3 10(-6)/degrees C, and Vitablocs Mark
      II had the lowest at 8.60 (SD 1.47) 3 10(-6)/degrees C. CONCLUSIONS: The 3
      ceramic materials significantly differed in all of the properties measured.
      Vitablocs Mark II was the hardest of the 3 materials, and IPS Empress CAD had the
      greatest flexure strength, flexural modulus, and fracture toughness.

PMID- 19107266
TI  - Flexural properties, microleakage, and degree of conversion of a resin
      polymerized with conventional light and argon laser.
AB  - OBJECTIVE: To evaluate the flexural strength, microleakage, and degree of
      conversion of a microhybrid resin polymerized with argon laser and halogen lamp.
      METHOD AND MATERIALS: For both flexural test and degree of conversion analysis, 5
      bar samples of composite resin were prepared and polymerized according to ISO
      4049. The halogen light-curing unit was used with 500 mW/cm(2) for 20 seconds and
      the argon laser with 250 mW for 10 and 20 seconds. Samples were stored in
      distilled water in a dark environment at 37 degrees C for 24 hours. The flexural
      property was quantified by a 3-point loading test. For the microleakage
      evaluation, 60 bovine incisors were used to prepare standardized Class 5
      cavities, which were restored and polished. Specimens were stored in distilled
      water for 24 hours at 37 degrees C and thermocycled 500 times (6 degrees C to 60
      degrees C). Specimens were then immersed in an aqueous solution of basic fuchsin
      for 24 hours. Longitudinal sections of each restoration were obtained and
      examined with a stereomicroscope for qualitative evaluation of microleakage.
      Fourier transform (FT)-Raman RFS 100/S spectrometer (Bruker) was used to analyze
      the degree of conversion. RESULTS: ANOVA showed no statistically significant
      differences of flexural strength between the photoactivation types evaluated in
      the flexural study. Microleakage data were statistically analyzed by Mann-Whitney
      and Kruskal-Wallis tests. Enamel margins resulted in a statistically lower degree
      of leakage than dentin margins. No statistically significant difference was found
      among the 3 types of photocuring studied. ANOVA also showed no statistically
      significant difference in the degree of conversion among the studied groups.
      CONCLUSION: According to the methodology used in this research, the argon laser
      is a possible alternative for photocuring, providing the same quality of
      polymerization as the halogen lamp. None of the photocured units tested in this
      study completely eliminated microleakage.

PMID- 19107267
TI  - Orthodontic and surgical approach to the treatment of bilaterally impacted
      maxillary canines: a case report.
AB  - Impaction of maxillary canines is a common orthodontic anomaly that causes facial
      and dentoalveolar system problems, both functional and esthetic. A combination of
      surgery and orthodontics is important in bringing impacted canines to their ideal
      position in the dental arch. In this case report of a 14-year-old patient with
      impacted right and left maxillary canines, the crowns of these teeth were
      surgically exposed, brackets were bonded, and light orthodontic forces were
      delivered for 2 years to align the teeth in the dental arch.

PMID- 19107268
TI  - Efficacy of pit and fissure sealing: long-term clinical observations.
AB  - OBJECTIVE: To investigate long-term clinical effects of fissure sealing in
      permanent teeth with regard to sealant retention, reduction of occlusal caries,
      and effect on the increment of smooth surface caries. METHOD AND MATERIALS: The
      study included 360 children aged 7 to 8 years with caries-free permanent teeth.
      Children were divided into 4 groups, and fissure sealing was performed as
      follows: group 1 -- 1 maxillary first molar and 1 mandibular first molar sealed;
      group 2 -- all first molars sealed; group 3 -- all molars and premolars sealed on
      eruption; group 4 -- controls, no teeth sealed. Materials used for sealing were
      Nuva-Seal (Caulk), Concise Brand White Sealant System (3M ESPE), and Concise
      Enamel Bond System (3M ESPE). Control examinations were performed over 15 years,
      every 6 months for 2 years and then every 12 months. RESULTS: Complete sealant
      retention after 15 years was observed in 22.0% of cases, and partial retention in
      35.0%. The degree of sealant retention affected the occurrence of occlusal caries
      in sealed teeth. Reduction in caries after 15 years was 36.0% when all first
      molars were sealed and 54.0% when all posterior teeth were sealed. Caries
      developed in 7.4% of teeth with complete sealant retention, in 15.0% of teeth
      with partial sealant retention, and in 31.0% of teeth with complete loss of
      sealant. CONCLUSIONS: The degree of sealant retention depends on the duration of
      observation and tooth type. The degree of caries reduction depends on the number
      of teeth sealed. Mean caries increment was lower in children with sealed teeth
      than in controls.

PMID- 19107269
TI  - Effect of accelerated aging on the color stability of feldspathic ceramic treated
      with various surface treatments.
AB  - OBJECTIVE: To investigate the effect of the accelerated aging process on the
      color stability of feldspathic ceramic treated with dual ion exchange, overglaze,
      polishing, and autoglaze surface treatments. METHOD AND MATERIALS: A total of 40
      disks (15 mm in diameter and 2 mm thick) of feldspathic ceramic were made in an
      A2 shade according to the manufacturer's recommendations. The samples were
      randomly divided into 4 groups: dual ion exchange, overglaze, polishing, and
      autoglaze. The samples were subjected to conditions in an accelerated aging
      machine for 150 and 300 hours. Differences in color before and after accelerated
      aging were calculated using spectrophotometric analyses. Overall color difference
      (DeltaE) was determined using the CIE L*a*b* system for measuring small color
      differences. Scanning electron microscopy was used to evaluate the surface
      texture of samples. Color difference data were evaluated statistically by Kruskal
      Wallis and Mann-Whitney U tests, with a significance level of .05. RESULTS: After
      150 and 300 hours of accelerated aging, color changes of the 4 surface treatment
      groups ranged between 0.35 and 1.31 DeltaE units. All DeltaE values were below a
      quantitative level that would be considered clinically acceptable. Autoglazed
      samples were the most color stable, followed by ion exchanged, overglazed, and
      polished test samples. CONCLUSIONS: All groups demonstrated color stability below
      a quantitative level that would be considered clinically acceptable, but long
      term clinical studies are necessary to verify these findings.

PMID- 19107270
TI  - Oral focal mucinosis.
AB  - Oral focal mucinosis is an uncommon clinicopathologic condition that is
      considered the oral counterpart of cutaneous focal mucinosis. It is a disease of
      unknown etiology where the connective tissue undergoes a focal myxoid
      degeneration. A literature review disclosed 47 published cases of oral focal
      mucinosis. An additional case is presented; the clinical and histologic
      differential diagnosis, sex, age, location, treatment, and recurrence are
      discussed.

PMID- 19107271
TI  - Metastasis of a bronchial carcinoma in the left condylar process.

PMID- 19107272
TI  - Optical aggregation of metal nanoparticles in a microfluidic channel for surface
      enhanced Raman scattering analysis.
AB  - Aggregated metal nanoparticles exhibit enhanced localized electromagnetic fields
      that enable highly sensitive vibrational spectroscopy analysis based on surface
      enhanced Raman scattering (SERS). We demonstrate SERS detection of organic
      analytes adsorbed to optically aggregated silver nanoparticles in a microfluidic
      device. The combination of optical tweezers and microfluidics technologies paves
      the way for novel lab-on-a-chip based plasmonic chemo/bio sensors and overcomes
      two important drawbacks of standard SERS sensing schemes; i.e. the renewal of
      nanofabricated metallic substrates and the difficulty of avoiding uncontrolled
      aggregation in metal colloids.

PMID- 19107273
TI  - On-demand microfluidic control by micropatterned light irradiation of a
      photoresponsive hydrogel sheet.
AB  - Novel on-chip fluid control strategies, on-demand formation of arbitrary
      microchannels and parallel control of multiple microvalves were successfully
      demonstrated by means of computer-controlled micropatterned light irradiation of
      a photoresponsive hydrogel sheet.

PMID- 19107274
TI  - Rapid and selective concentration of microparticles in an optoelectrofluidic
      platform.
AB  - We demonstrate rapid manipulation and selective concentration of microparticles
      using AC electrokinetics such as dielectrophoresis (DEP) and AC electro-osmosis
      (ACEO) in an optoelectrofluidic platform based on a liquid crystal display (LCD).
      When 10 V bias at 10 kHz was applied to the optoelectrofluidic device, only the 1
      microm-diameter polystyrene particles were concentrated into the projected LCD
      image patterns and closely packed, forming the crystalline structure by ACEO
      flow, while the 6 microm-diameter particles were repelled by negative DEP forces.
      We have characterized this frequency-dependency of the optoelectrofluidic
      particle behavior according to the particle diameter. On the basis of these
      results, we can rapidly concentrate the 1 microm-diameter particles and separate
      them from the 6 microm particles, by applying an AC signal of 10 kHz frequency.
      This novel technique can be applied to rapidly concentrate, separate and pattern
      micro-/nanoparticles in many biological and chemical applications.

PMID- 19107275
TI  - A microfluidic abacus channel for controlling the addition of droplets.
AB  - This paper reports the first use of the abacus-groove structure to handle
      droplets in a wide microchannel, with no external forces integrated to the system
      other than the pumps. Microfluidic abacus channels are demonstrated for the
      sequential addition of droplets at the desired location. A control channel which
      is analogous to biasing in electronics can also be used to precisely determine
      the number of added droplets, when all other experimental conditions are fixed
      including the size of the droplets and the frequency of droplet-generation. The
      device allows programmable and autonomous operations of complex two-phase
      microfluidics as well as new applications for the method of analysis and
      computations in lab-on-a-chip devices.

PMID- 19107276
TI  - Lab-on-a-chip for ultrasensitive detection of carbofuran by enzymatic inhibition
      with replacement of enzyme using magnetic beads.
AB  - In this paper an ultrasensitive method to determine toxicity due to pesticides in
      a glass lab-on-a-chip by means of enzymatic inhibition of acetylcholinesterase
      immobilised on magnetic beads is described. The reproducible insertion of a
      controlled amount of enzyme-coupled magnetic beads inside the chip channel and
      their immobilisation in a capture region with the aid of a magnetic field has
      been optimised. This procedure enables the easy renewal of the biosensing
      material after each determination in a highly reproducible manner. Several
      operational parameters such as the working potential for the selective detection
      of thiocholine (TCh) on a platinum disc electrode, the TCh detection
      reproducibility and sensitivity, the electroosmotic flow driving voltage and the
      inhibition time were also evaluated or optimised. The detection of carbofuran
      (one of the most toxic carbamate pesticides) has been achieved down to the
      nanomolar level.

PMID- 19107278
TI  - Characterization of drug metabolites and cytotoxicity assay simultaneously using
      an integrated microfluidic device.
AB  - An integrated microfluidic device was developed for the characterization of drug
      metabolites and a cytotoxicity assay simultaneously. The multi-layer device was
      composed of a quartz substrate with embedded separation microchannels and a
      perforated three-microwell array containing sol-gel bioreactors of human liver
      microsome (HLM), and two PDMS layers. By aligning the microwell array on the
      quartz substrate with cell culture chambers on the bottom PDMS layer, drug
      metabolism studies related to functional units, including metabolite generation,
      detection and incubation with cultured cells to assess metabolism induced
      cytotoxicity, were all integrated into the microfluidic device. To validate the
      feasibility of drug metabolism study on the microfluidic chip, UDP
      glucuronosyltransferase (UGT) metabolism of acetaminophen (AP) and its effect on
      hepG2 cytotoxicity were studied first. Then metabolism based drug-drug
      interaction between AP and phenytoin (PH), which resulted in increased hepG2
      cytotoxicity, was proved on this device. All this demonstrated that the developed
      microfluidic device could be a potential useful tool for drug metabolism and
      metabolism based drug-drug interaction research.

PMID- 19107277
TI  - Experimentally and theoretically observed native pH shifts in a nanochannel
      array.
AB  - Lab-on-a-chip (LOC) technology provides a powerful platform for simultaneous
      separation, purification, and identification of low concentration multicomponent
      mixtures. As the characteristic dimension of LOC devices decreases down to the
      nanoscale, the possibility of containing an entire lab on a single chip is
      becoming a reality. This research examines one of the unique physical
      characteristics of nanochannels, in which native pH shifts occur. As a result of
      the electrical double layer taking up a significant portion of a 100 nm wide
      nanochannel, electroneutrality no longer exists in the channel causing a radial
      pH gradient. This work describes experimentally observed pH shifts as a function
      of ionic strength using the fluorescent pH indicator 5-(and-6)-carboxy SNARF-1
      and compares it to a model developed using Comsol Multiphysics. At low ionic
      strengths (approximately 3 mM) the mean pH shift is approximately 1 pH unit
      whereas at high ionic strengths (approximately 150 mM) the mean pH shift is
      reduced to 0.1 pH units. An independent analysis using fluorescein pH indicator
      is also presented supporting these findings. Two independent non-linear
      simulations coupling the Nernst-Planck equation describing transport in ionic
      solutions subjected to an electric field and Poisson's equation to describe the
      electric field as it relates to the charge distribution are solved using a finite
      element solver. In addition, the effects of chemical activities are considered in
      the simulations. The first numerical simulation is based on a surface zeta
      potential which significantly underestimates the experimental results for most
      ionic strengths. A modified model assuming that SNARF and fluorescein molecules
      are able to diffuse into the hydrolyzed SiO2 phase, and in the case of the SNARF
      molecule, able to bind to neutral regions of the SiO2 phase agrees quantitatively
      with experimental results.

PMID- 19107279
TI  - Additional amplifications of SERS via an optofluidic CD-based platform.
AB  - In this paper, signal amplifications of surface-enhanced Raman scattering (SERS)
      are realized by an optofluidic compact disc (CD)-based preconcentration method
      for effective label-free environmental and biomolecular detections. The
      preconcentration of target molecules is accomplished through the accumulation of
      adsorbed molecules on SERS-active sites by repeating a 'filling-drying' cycle of
      the assay solution in the optofluidic CD platform. After 30 cycles, the clear and
      high SERS signal of rhodamine 6G of 1 nM is readily detected. In addition to the
      preconcentration-based signal amplification by the optofluidic SERS system on the
      CD platform, we introduce a controlled precipitation of gold nanoparticles by
      CuSO4 for SERS substrates. This method provides high-throughput, high-sensitive
      and large-area uniform SERS substrates on the optofluidic CD platform. The
      uniform SERS signals from different positions in spots of 3 mm2 on the different
      CDs gives us confidence in the reliability and stability of our SERS substrates.

PMID- 19107280
TI  - Versatile microfluidic total internal reflection (TIR)-based devices: application
      to microbeads velocity measurement and single molecule detection with upright and
      inverted microscope.
AB  - A poly(dimethylsiloxane) (PDMS) chip for Total Internal Reflection (TIR)-based
      imaging and detection has been developed using Si bulk micromachining and PDMS
      casting. In this paper, we report the applications of the chip on both inverted
      and upright fluorescent microscopes and confirm that two types of sample delivery
      platforms, PDMS microchannel and glass microchannel, can be easily integrated
      depending on the magnification of an objective lens needed to visualize a sample.
      Although any device configuration can be achievable, here we performed two
      experiments to demonstrate the versatility of the microfluidic TIR-based devices.
      The first experiment was velocity measurement of Nile red microbeads with nominal
      diameter of 500 nm in a pressure-driven flow. The time-sequenced fluorescent
      images of microbeads, illuminated by an evanescent field, were cross-correlated
      by a Particle Image Velocimetry (PIV) program to obtain near-wall velocity field
      of the microbeads at various flow rates from 500 nl/min to 3000 nl/min. We then
      evaluated the capabilities of the device for Single Molecule Detection (SMD) of
      fluorescently labeled DNA molecules from 30 bp to 48.5 kbp and confirm that DNA
      molecules as short as 1105 bp were detectable. Our versatile, integrated device
      could provide low-cost and fast accessibility to Total Internal Reflection
      Fluorescent Microscopy (TIRFM) on both conventional upright and inverted
      microscopes. It could also be a useful component in a Micro-Total Analysis System
      (micro-TAS) to analyze nanoparticles or biomolecules near-wall transport or
      motion.

PMID- 19107282
TI  - In-situ measurement of cellular microenvironments in a microfluidic device.
AB  - We report on the integration of optical microsensors into a cell culture
      microchannel device. We demonstrate the possibility of measuring the glucose and
      oxygen concentrations in the microenvironment of the mammalian cells cultured in
      a microchannel device. Furthermore, cell proliferation and morphology could be
      monitored microscopically while these measurements were being made. Through the
      use of multiple sensors along the length of the microchannel, concentration
      gradients of various metabolites, such as oxygen, as well as the effects of cell
      uptake and perfusion rate of growth medium on these gradients could be studied.
      As such, the system allowed real-time observations of the cells' response to
      their chemical microenvironment. Our approach allows cell culture and cell assays
      to be performed simultaneously in an integrated microchannel system with
      potential applications as a research tool or drug screening method.

PMID- 19107281
TI  - A microfluidic chip for real-time studies of the volume of single cells.
AB  - We report a microfluidic chip that is capable of measuring volume changes in
      single cells in real-time. Single eukaryotic cells were immobilized in the
      sensing area and changes in volume in response to hypotonic challenges and drugs
      were measured using the electrical impedance method. Experiments on MDCK cells
      showed that the maximum swelling and the time course of swelling vary between
      individual cells following hypotonic stimulation. The microfluidic chip allows,
      rapid and convenient change of solutions, enabling detailed studies of various
      drugs and chemicals that may play important role in cell physiology at the single
      cell level.

PMID- 19107283
TI  - Rolled-up transparent microtubes as two-dimensionally confined culture scaffolds
      of individual yeast cells.
AB  - Transparent oxide rolled-up microtube arrays were constructed on Si substrates by
      the deposition of a pre-stressed oxide layer on a patterned photoresist
      sacrificial layer and the subsequent removal of this sacrificial layer. These
      microtubes as well as their arrays can be well positioned onto a chip for further
      applications, while their dimensions (e.g. length, diameter and wall thickness)
      are controlled by tunable parameters of the fabrication process. Due to the
      unique tubular structure and optical transparency, such rolled-up microtubes can
      serve as well-defined two-dimensionally (2D) confined cell culture scaffolds. In
      our experiments, yeast cells exhibit different growth behaviors (i.e. their
      arrangement) in microtubes with varied diameters. In an extremely small microtube
      the yeast cell becomes highly elongated during growth but still survives.
      Detailed investigations on the behavior of individual yeast cells in a single
      microtube are carried out in situ to elucidate the mechanical interaction between
      microtubes and the 2D confined cells. The confinement of tubular channels causes
      the rotation of cell pairs, which is more pronounced in smaller microtubes,
      leading to different cellular assemblies. Our work demonstrates good capability
      of rolled-up microtubes for manipulating individual and definite cells, which
      promises high potential in lab-on-a-chip applications, for example as a bio
      analytic system for individual cells if integrated with sensor functionalities.

PMID- 19107284
TI  - Cell migration into scaffolds under co-culture conditions in a microfluidic
      platform.
AB  - Capillary morphogenesis is a complex cellular process that occurs in response to
      external stimuli. A number of assays have been used to study critical regulators
      of the process, but those assays are typically limited by the inability to
      control biochemical gradients and to obtain images on the single cell level. We
      have recently developed a new microfluidic platform that has the capability to
      control the biochemical and biomechanical forces within a three dimensional
      scaffold coupled with accessible image acquisition. Here, the developed platform
      is used to evaluate and quantify capillary growth and endothelial cell migration
      from an intact cell monolayer. We also evaluate the endothelial cell response
      when placed in co-culture with physiologically relevant cell types, including
      cancer cells and smooth muscle cells. This resulted in the following
      observations: cancer cells can either attract (MTLn3 cancer cell line)
      endothelial cells and induce capillary formation or have minimal effect (U87MG
      cancer cell line) while smooth muscle cells (10T 1/2) suppress endothelial
      activity. Results presented demonstrate the capabilities of this platform to
      study cellular morphogenesis both qualitatively and quantitatively while having
      the advantage of enhanced imaging and internal biological controls. Finally, the
      platform has numerous applications in the study of angiogenesis, or migration of
      other cell types including tumor cells, into a three-dimensional scaffold or
      across an endothelial layer under precisely controlled conditions of mechanical,
      biochemical and co-culture environments.

PMID- 19107285
TI  - Integrated two-step gene synthesis in a microfluidic device.
AB  - Herein we present an integrated microfluidic device capable of performing two
      step gene synthesis to assemble a pool of oligonucleotides into genes with the
      desired coding sequence. The device comprised of two polymerase chain reactions
      (PCRs), temperature-controlled hydrogel valves, electromagnetic micromixer,
      shuttle micromixer, volume meters, and magnetic beads based solid-phase PCR
      purification, fabricated using a fast prototyping method without lithography
      process. The fabricated device is combined with a miniaturized thermal cycler to
      perform gene synthesis. Oligonucleotides were first assembled into genes by
      polymerase chain assembly (PCA), and the full-length gene was amplified by a
      second PCR. The synthesized gene was further separated from the PCR reaction
      mixture by the solid-phase PCR purification. We have successfully used this
      device to synthesize a green fluorescent protein fragment (GFPuv) (760 bp), and
      obtained comparable synthesis yield and error rate with experiments conducted in
      a PCR tube within a commercial thermal cycler. The resulting error rate
      determined by DNA sequencing was 1 per 250 bp. To our knowledge, this is the
      first microfluidic device demonstrating integrated two-step gene synthesis.

PMID- 19107287
TI  - Extension of the Helmholtz-Smoluchowski velocity to the hydrophobic microchannels
      with velocity slip.
AB  - Electrokinetic flows through hydrophobic microchannels experience velocity slip
      at the microchannel wall, which affects volumetric flow rate and solute retention
      time. The usual method of predicting the volumetric flow rate and velocity
      profile for hydrophobic microchannels is to solve the Navier-Stokes equation and
      the Poisson-Boltzmann equation for the electric potential with the boundary
      condition of velocity slip expressed by the Navier slip coefficient, which is
      computationally demanding and defies analytic solutions. In the present
      investigation, we have devised a simple method of predicting the velocity
      profiles and volumetric flow rates of electrokinetic flows by extending the
      concept of the Helmholtz-Smoluchowski velocity to microchannels with Navier slip.
      The extended Helmholtz-Smoluchowski velocity is simple to use and yields accurate
      results as compared to the exact solutions. Employing the extended Helmholtz
      Smoluchowski velocity, the analytical expressions for volumetric flow rate and
      velocity profile for electrokinetic flows through rectangular microchannels with
      Navier slip have been obtained at high values of zeta potential. The range of
      validity of the extended Helmholtz-Smoluchowski velocity is also investigated.

PMID- 19107286
TI  - Augmenting microgel flow via receptor-ligand binding in the constrained
      geometries of microchannels.
AB  - We investigated the flow dynamics of biotin-conjugated microgel capsules in
      avidin-conjugated microchannel constrictions. Microgels were prepared using a
      microfluidic assembly approach. Biotinylated microgels passing through avidin
      modified constrictions slowed relative to several control systems. This effect
      was observed below a critical velocity of the microgels in the channel-at-large.
      The reduction in microgel velocity in the constriction occurred for several
      different sizes of microgels and orifices. Soft compliant microgels showed a
      lower velocity in the constriction relative to rigid microgels with the same
      concentration of biotin on the surface, due to the ability of the softer
      microgels to deform in the orifice and maximize their surface area when in
      contact with the orifice wall.

PMID- 19107288
TI  - Effective mixing of laminar flows at a density interface by an integrated
      ultrasonic transducer.
AB  - An acoustic mixer for glass channel microfluidic systems is presented. An
      acoustic standing wave, perpendicular to the fluid flow, is generated by the
      excitation of a miniaturized piezoelectric transducer operated around 10 MHz. The
      transducer is fabricated into a planar printed circuit board structure,
      constituting the bottom channel wall, which makes the mixer simple to integrate
      with a wide selection of microfluidic channel designs. The mixing occurs at a
      fluid-fluid density interface due to the acoustic radiation force; an analytical
      expression is derived to qualitatively describe this phenomenon. Only a small
      density difference in the range of 2-5% is required to achieve 150-270% peak
      broadening of a fluorescent sample between sheath flows, which we use as a
      measure of the mixing efficiency. The mixing efficiency is measured with regard
      to its sensitivity to the density difference, the fluid velocity and the
      transducer driving frequency. Transducers at different positions along the
      microchannel make it possible to compare the mixing of straight versus diagonal
      flows across the transducer surface. We finally demonstrate enhanced chemical
      lysis of E. coli K12 cells in the device due to active fluid mixing.

PMID- 19107289
TI  - 384-channel parallel microfluidic cytometer for rare-cell screening.
AB  - We have constructed a 384-channel parallel microfluidic cytometer (PMC). The
      multichannel architecture allows 384 unique samples for a cell-based screen to be
      read out in approximately 6-10 min, about 30-times the speed of a conventional
      fluorescence-activated cytometer system (FACS). This architecture also allows the
      signal integration time to be varied over a larger range than is practical in
      single-channel FACS and is suitable for detection of rare-cells in a high
      background of negatives. The signal-to-noise advantages have been confirmed by
      using the system to count rare clonal osteocytes in the most difficult early
      stages of an expression-cloning screen for the carboxy-terminal parathyroid
      hormone receptor (CPTHR). This problem requires finding several dozen positive
      cells in a background of one million negatives. The system is automated around a
      scanning laser confocal detector and a 96-tip robotic pipettor and can maintain
      in vitro cultures on-system in 384-well plates. It is therefore directly
      practical for biology applications using existing high-throughput culture
      facilities. The PMC system lends itself to high-sample-number cytometry with an
      unusual capability for time synchronization and rare-cell sensitivity. A limited
      ability to handle large sample numbers has restricted applications of single
      channel FACS in combinatorial cell assays; therefore the PMC could have a
      significant application in high-throughput screening.

PMID- 19107290
TI  - Single cell detection using a glass-based optofluidic device fabricated by
      femtosecond laser pulses.
AB  - We demonstrate the fabrication of integrated three-dimensional microchannel and
      optical waveguide structures inside fused silica for the interrogation and
      processing of single cells. The microchannels are fabricated by scanning
      femtosecond laser pulses (523 nm) and subsequent selective wet etching process.
      Optical waveguides are additionally integrated with the fabricated microchannels
      by scanning the laser pulse train inside the glass specimen. Single red blood
      cells (RBC) in diluted human blood inside of the manufactured microchannel were
      detected by two optical schemes. The first involved sensing the intensity change
      of waveguide-delivered He-Ne laser light (632.8 nm) induced by the refractive
      index difference of a cell flowing in the channel. The other approach was via
      detection of fluorescence emission from dyed RBC excited by Ar laser light (488
      nm) delivered by the optical waveguide. The proposed device was tested to detect
      23 fluorescent particles per second by increasing the flow rate up to 0.5 microl
      min(-1). The optical cell detection experiments support potential implementation
      of a new generation of glass-based optofluidic biochip devices in various single
      cell treatment processes including laser based cell processing and sensing.

PMID- 19107291
TI  - Label-free determination of protein-surface interaction kinetics by ionic
      conductance inside a nanochannel.
AB  - We have developed a label-free conductometric platform for the rapid measurement
      of kinetics parameters for the adsorption and desorption of proteins on surfaces.
      Adsorbed Bovine Serum Albumin (BSA) has been detected electrically with response
      times in the minute range, and kinetic models were elaborated and compared to the
      measurements. The device presents similar characteristics to Surface Plasmon
      Resonance (SPR) immunosensors, but takes advantage of a simpler, low-cost
      electronic measurement unit.

PMID- 19107292
TI  - Manipulation of gel emulsions by variable microchannel geometry.
AB  - In this article we investigate the morphology and manipulation of monodisperse
      emulsions at high dispersed phase volume fractions (gel emulsions) in a
      microfluidic environment. Confined monodisperse gel emulsions self-organize into
      well-ordered droplet arrangements, which may be stable or metastable, depending
      on the geometry of the confining microchannel. Three arrangements are considered,
      in which the droplets are aligned in a single file, a two row, or a three row
      arrangement. We explore the potential for induced transitions between these
      distinct droplet arrangements as a tool for droplet-based microfluidic
      processing. Transitions are readily achieved by means of localized (geometrical)
      features in channel geometry, however the onset of the transition is strongly
      dependent on the subtleties of the microfluidic system, e.g. volume fraction,
      droplet size, and feature dimensions. The transitions can be achieved via fixed
      channel features or, when the continuous phase is a ferrofluid, by a virtual
      channel constriction created using a magnetic field.

PMID- 19107293
TI  - Simple, robust storage of drops and fluids in a microfluidic device.
AB  - We describe a single microfluidic device and two methods for the passive storage
      of aqueous drops in a continuous stream of oil without any external control but
      hydrodynamic flow. Advantages of this device are that it is simple to
      manufacture, robust under operation, and drops never come into contact with each
      other, making it unnecessary to stabilize drops against coalescence. In one
      method the device can be used to store drops that are created upstream from the
      storage zone. In the second method the same device can be used to simultaneously
      create and store drops from a single large continuous fluid stream without
      resorting to the usual flow focusing or T-junction drop generation processes.
      Additionally, this device stores all the fluid introduced, including the first
      amount, with zero waste. Transport of drops in this device depends, however, on
      whether or not the aqueous drops wet the device walls. Analysis of drop transport
      in these two cases is presented. Finally, a method for extraction of the drops
      from the device is also presented, which works best when drops do not wet the
      walls of the chip.

PMID- 19107294
TI  - Living anionic polymerization using a microfluidic reactor.
AB  - Living anionic polymerizations were conducted within aluminum-polyimide
      microfluidic devices. Polymerizations of styrene in cyclohexane were carried out
      at various conditions, including elevated temperature (60 degrees C) and high
      monomer concentration (42%, by volume). The reactions were safely maintained at a
      controlled temperature at all points in the reactor. Conducting these reactions
      in a batch reactor results in uncontrolled heat generation with potentially
      dangerous rises in pressure. Moreover, the microfluidic nature of these devices
      allows for flexible 2D designing of the flow channel. Four flow designs were
      examined (straight, periodically pinched, obtuse zigzag, and acute zigzag
      channels). The ability to use the channel pattern to increase the level of mixing
      throughout the reactor was evaluated. When moderately high molecular mass
      polymers with increased viscosity were made, the patterned channels produced
      polymers with narrower PDI, indicating that passive mixing arising from the
      channel design is improving the reaction conditions.

PMID- 19107295
TI  - Towards lab-on-a-chip approaches in real analytical domains based on microfluidic
      chips/electrochemical multi-walled carbon nanotube platforms.
AB  - "Lab-on-a-chip" approaches based on the novel marriage between an electrokinetic
      microfluidic platform and nanotechnology is proposed for analytical domains.
      Conceptually, the analytical challenges are linked with the analytical promises
      offered from the integration of lab-on-a-chip and nanotechnologies. The
      analytical suitability of the electrokinetic microfluidic platform with multi
      walled carbon nanotubes as detectors is proposed based on its dual format/use as
      a flow and separation system, independently. Two relevant applications of high
      significance, determination of total isoflavones and fast detection of
      antioxidant profiles were chosen to demonstrate their analytical potential. For
      both analytical uses, the target challenges, the strategy proposed, the expected
      role of microfluidics and carbon nanotubes and future prospects are discussed and
      demonstrated. A good analytical performance of the proposed microfluidic platform
      in terms of reliability, versatility and fast analytical solutions is
      demonstrated.

PMID- 19107296
TI  - An indirect microfluidic flow injection analysis (FIA) system allowing diffusion
      free pumping of liquids by using tetradecane as intermediary liquid.
AB  - We suggest an indirect microfluidic flow injection analysis (FIA) system which
      uses tetradecane (C14H30) as intermediary liquid allowing the diffusion free
      handling of liquids in a fluidic system which is suitable for single use
      applications as required, e.g., biomedical applications.

PMID- 19107297
TI  - [Health primary care reform and mother-child health objetives: a proposal from
      pediatrics on how to reconsider and agree upon them].

PMID- 19107298
TI  - [Family-physician communication when a child dies in Pediatric Intensive Care:
      good intentions are not enough].

PMID- 19107299
TI  - [The defense of our language: a barren effort?].

PMID- 19107300
TI  - [Impact of folic acid fortification on women's nutritional status and on the
      prevalence of neural tube defects].
AB  - INTRODUCTION: In 2003 iron and folic acid fortification of wheat flour became
      mandatory in Argentina. Folate nutritional status was assessed in a national
      probabilistic sample of women 10-49 years old and pregnant women. Changes in the
      prevalence of neural tube defects (NTDs) were evaluated before and after
      fortification. POPULATION AND METHODS: Data from the National Nutritional and
      Health Survey done in 2005 were used for folate intakes (24 hs dietary recall)
      and serum levels. Fetal and infant mortality rates for NTDs were assessed in the
      period 2000-2006 from Vital Statistics Series, based on birth and death
      certificates. Prevalence of NTDs in hospital discharge statistics were analyzed
      in the pre and post fortification period. RESULTS: Median folate intakes were 532
      and 821 microg/ day in women 10-49 years-old and pregnant women, respectively. In
      both groups, folic acid from wheat flour represented 245 and 331 microg/day.
      Serum folate was assessed in 5.322 women 10-49 years old and in 1.321 pregnant
      women. Prevalence of serum folate concentration <3 ng/mL was 0.8% in women of
      child-bearing age and 2.7% in pregnant women. Mortality rate due to anencephaly
      in 2000-2003 was 53.1 per 100.000 births and decreased to 23.3 per 100.000 births
      in 2005-2006. Spina bifida mortality rate decreased 67% in the same period. In a
      similar way, hospital discharge statistics showed a decrease of 54% for
      anencephaly, 33% for encephalocele, and 45% for spina bifida between 2000 and
      2005. CONCLUSIONS: Food fortification with folic acid was associated with
      adequate intakes and serum folate levels in women. Concurrently, NTDs prevalence
      and mortality showed a significant reduction.

PMID- 19107301
TI  - [Child abuse: an interdisciplinary management experience].
AB  - INTRODUCTION: Child abuse constitutes one of the most frequent forms of family
      violence. The following study tries to demonstrate the situation that arises in
      the city of Mercedes, Corrientes, Argentina, and to establish some associations
      about that matter. POPULATION, MATERIAL AND METHODS: A series of 128 cases of
      abused children is presented, between 0 and 19 years old, attended from November
      1998 to November 2002, in Moiru, Center of prevention, direction, attendance and
      qualification in social conducts of risk that works in Mercedes. RESULTS: 56% of
      physical abuse; 30% of sexual abuse; 10% of neglect; 3% of emotional abuse and 1%
      of syndrome of Munchaussen was detected, with a similar distribution by sexes in
      the total population. Demographic variables and certain associations in cases of
      physical abuse and sexual abuse are indicated. A significant association between
      mothers victims of domestic violence and physical abuse towards their children
      was demonstrated. CONCLUSIONS: 128 young boys and girls were seen in our center.
      It is considered that a significant population was treated where physical abuse
      and sexual abuse appears as most relevant.

PMID- 19107302
TI  - [Comparing Argentinian reference with WHO standards for the anthropometric
      evaluation of children less than 5 year-old].
AB  - INTRODUCTION: The new WHO growth standards, were the result of a multicenter
      growth reference study, performed on a sample of children with rigorous criteria
      of health, with families that had complied with the health recommendations that
      are made in the field of breastfeeding and not smoking. OBJECTIVE: To compare the
      argentine references with the WHO standard for the anthropometric evaluation of a
      population of children under 5 years. POPULATION: 474 children younger than 5
      years old who attended the Municipal Health Centers during October 2004. MATERIAL
      AND METHODS: Children were weighed and measured with instruments and techniques
      standardized by SAP. The study design was observational, cross-sectional,
      descriptive. We used EPI6/ ANTCONV for Argentine reference and ANTRHRO 2005 for
      WHO standard T test for two samples, P (T < t) two tails, and Chi 2. RESULTS:
      Total 474, 231 boys and 243 girls. Height/ age minor - 2 DS: Argentine reference=
      39 (8.2%) and WHO= 58 (12.2%), not significant. Weight/age minor -2DS: Argentine
      reference= 24 (5.1%) and WHO= 10 (Chi 2 p = 0.014). CONCLUSIONS: WHO standards,
      from 12 months on, selected the largest number of children with short stature,
      and, regarding weight, it happened the opposite, they selected less children with
      low weight/age.

PMID- 19107303
TI  - [Evaluation of two standardized methods for chest radiographs interpretation in
      children with pneumonia].
AB  - OBJECTIVE: To evaluate the accuracy of World Health Organization (WHO) method of
      interpreting chest radiographs on identifying young children with bacterial
      pneumonia, and to compare its accuracy with other method. METHODS: Chest
      radiographs from children aged under 5 years old hospitalized for pneumonia, with
      microbiological evidence of bacterial or viral infection, were evaluated by 3
      observers blinded to other data (pediatrician [P], pulmonologist [N], radiologist
      [R]) according to WHO and Khamapirad scores. A WHO score=1 and a Khamapirad score
      >2 were selected as the thresholds suggesting bacterial pneumonia. The
      relationship between radiographic scores and etiology was evaluated using chi
      square. Sensitivity (Se), specificity (Sp), positive (PPV) and negative (NPV)
      predictive values for predicting bacterial pneumonia were calculated.
      Interobserver agreement (P vs. N vs. R) was calculated (kappa). RESULTS: 108
      chest radiographs were evaluated (87 viral, 21 bacterial). WHO score= 1 was
      associated with bacterial pneumonia (p <0.001; OR= 6.4; CI 95%= 1.629.7),
      achieving a Se= 85%, Sp= 51%, PPV= 30%, NPV= 93%. Khamapirad score >2, evaluated
      by P, was also associated with bacterial pneumonia (p <0.0008; OR= 6.31; CI 95%=
      1.8-24.4), achieving a Se= 80%, Sp= 59%, PPV= 32% NPV= 92%. Interobserver
      agreement was slightly better using WHO score (P vs. N= 0.82, P vs. R= 0.69, N
      vs. R= 0.85) than Khamapirad score (P vs. N= 0.48, P vs. R= 0.69, N vs. R= 0.82).
      CONCLUSIONS: Both methods showed similar accuracy in order to identify bacterial
      pneumonia. WHO score is simpler than Khamapirad score and showed a better
      interobserver agreement.

PMID- 19107304
TI  - [Antibiotics prescription in infants hospitalized with respiratory syncytial
      virus pneumonia].
AB  - INTRODUCTION: Although not useful, antibiotics are commonly prescribed in infants
      with viral pneumonia. OBJECTIVE: To compare initial prescription and suspension
      rates of antibiotics in infants hospitalized with pneumonia by respiratory
      syncytial virus (RSV) in 2002, when introducing the viral testing, and in 2007,
      after 5 years of this practice. POPULATION AND METHODS: Children aged under 13
      months hospitalized for RSV pneumonia during two years (2002 and 2007) were
      included. Prescription and discontinuation of antibiotics were registered. Data
      were analyzed using Chi squared and T tests, assuming p <0.05 as significance
      level. RESULTS: Antibiotics were prescribed in 57% (40/70) of patients in 2002
      and 46% of then (29/63) in 2007. After achieving RSV diagnosis, antibiotics were
      more frequently discontinued in 2007 than in 2002 (31/63 vs. 14/70; p= 0.012; OR:
      3.73; IC 95%:1.1512.49). CONCLUSION: Although antibiotic empirical prescription
      rate was similar in both periods, after achieving RSV diagnosis antibiotics were
      more frequently discontinued in 2007.

PMID- 19107305
TI  - [Investigation of the causes of infant sudden unexpected death in children
      younger than one year in Bariloche city and surrounding areas].
AB  - INTRODUCTION: In the beginning of 2002 there were an unusually high number of
      sudden unexpected infant deaths. A prospective study was started to determine the
      cause of unexpected deaths in infants younger than 1 year. AIMS: Investigate the
      possible causes of sudden and unexpected death in infants of Bariloche and
      surrounding areas, using a protocol created for that purpose. METHODS: All
      infants under 1 year of age who died unexpectedly between May 2002 and April 2007
      were studied. A complete physical examination, a thorough interrogation to the
      parents and an autopsy were performed. According to the findings a definitive
      diagnosis was made on each case. RESULTS: During the study period 10 infants
      younger than 1 year died. One case was excluded because the autopsy could not be
      done. The mean age was 74 days, 6 were males. All died while sleeping and no sign
      of disease were noticed in any case. In 6 cases, the autopsy findings explained
      the death. In the 3 others no cause for the death was found. CONCLUSIONS: The
      implementation of this protocol allowed to find out the cause of death in 6
      cases, that could not have been achieved without the autopsy.

PMID- 19107306
TI  - [Analgesia and sedation in pediatric procedures. Part 2: Requirements and drugs].

PMID- 19107307
TI  - [Use of sterile petrolatum for extravasation injury in a premature infant].
AB  - The skin of premature infants is an ineffective barrier. The stratum corneum is
      thinner than that found in full-term infants. We report on a premature patient
      with extravasation injury from sodium bicarbonate. Daily treatment with sterile
      petrolatum resulted in restitutio ad integrum.

PMID- 19107308
TI  - [Kikuchi-Fujimoto disease: case report].
AB  - Kikuchi-Fujimoto disease is a self-limited condition of young adults, that
      usually involves the cervical lymph nodes and is associated with persistent
      hyperthermia. Diagnosis is based on characteristic pathologic findings, that
      allows the differential diagnosis with other similar clinical conditions. We
      report one case of Kikuchi-Fujimoto disease in a 12 year old girl and review the
      world literature.

PMID- 19107309
TI  - [Nasal septal abscess].
AB  - A nasal septal abscess (NA) is defined as a collection of pus between the
      cartilage or bony septum and its normally applied mucoperichondrium or
      mucoperiostium. It is an uncommon disease which should be suspected in a patient
      with acute onset of nasal obstruction and recent history of nasal trauma,
      periodontal infection or an inflammatory process of the rhinosinusal region. We
      report a case of an 8-year-old boy with bilateral NA caused by community-acquired
      methicillin-resistant Staphylococcus aureus(MR-CO) in order to emphasize the
      importance of prompt diagnosis and adequate treatment to prevent the potentially
      dangerous spread of infection and the development of severe functional and
      cosmetic sequelae.

PMID- 19107310
TI  - [Primary pyomyositis due to community acquired methicillin resistant
      Staphylococcus aureus].
AB  - Primary pyomyositis is an acute or subacute bacterial infection of skeletal
      muscle characterized by the formation of intramuscular localized abscess without
      a previous adjoining or remote infection. Although it is not frequent in our
      population, it is increasing because of community-acquired methicillin-resistant
      Staphylococcus aureus (CA-MRSA) emergency. For an early diagnosis and to avoid
      secondary complications a high degree of clinical suspicion is required. We
      report a case of primary pyomyositis in a boy without an underlying condition or
      previous infection.

PMID- 19107311
TI  - [Superior mesenteric artery syndrome (Wilkie syndrome): case report].
AB  - Superior mesenteric artery syndrome is an uncommon cause of upper
      gastrointestinal tract obstruction. The syndrome results from compression of the
      third portion of duodenum as it crosses underneath the superior mesenteric
      artery, related to conditions that reduce the aortomesenteric angle (acute weight
      loss) or after scoliosis surgery. Patients may present symptoms of
      gastrointestinal obstruction, such as upper abdominal distension and epigastric
      tenderness, usually relieved by posture changing. Diagnose must be complemented
      with an upper gastrointestinal barium-contrast radiography. Conservative
      treatment is usually effective with early diagnosis. Surgery is needed when
      conservative measures are ineffective. We present the case of a 18 year-old
      patient with Wilkie's syndrome secondary to scoliosis surgery. The patient
      presented symptoms of gastrointestinal obstruction, and diagnosis was confirmed
      with upper gastrointestinal barium-contrast radiography. The patient started
      conservative treatment with proper positioning after eating and nutritional
      support to provide optimal calories supply.

PMID- 19107312
TI  - [Chronic wheezing child and type "D" double aortic arch: case report].
AB  - Right aortic arch with retroesophageal left innominate artery is an unusual
      pathology. The presence of patent ductus arteriosus, or left ductal ligament,
      does complete the vascular ring (Type "D" double aortic arch). In infants with
      dysphagia, stridor and/ or recurrent wheezing, presence of vascular rings may be
      suspected. In older patients this diagnosis is less common. Children in school
      age or older with risk factors, positive bronchodilator test and bad evolution,
      could have other unusual etiologies. We report an 8 year old patient with
      previous diagnosis of asthma with inadequate response to treatment in whom this
      non-frequent type of vascular ring was confirmed.

PMID- 19107313
TI  - [Chronic renal failure, dialysis and transplant: multicentric study: 1996-2003].
AB  - OBJECTIVE: The multicentric study of chronic renal failure, dialysis and
      transplant started in 1996 by the Nephrology Committee of the Argentine
      Pediatrics Society with the aim of knowing the development characteristics of
      children with this pathology. POPULATION, MATERIAL AND METHODS: The study
      included children and adolescents on conservative treatment, dialysis or
      transplant who have registered any of the three modalities before being 19 year
      old, since january 1996 to december 2003. The statistical analysis was made with
      the statistical software SAS; in order to calculate the survival curve, the
      method employed was Kaplan-Meier and the standardized height and weight z-scores
      were calculated. RESULTS: In this report, there is data related to 710 patients
      with chronic renal failure, under conservative treatment 34.2%, dialysis 57.6%
      and transplant 29.5%. The end-stage renal disease incidence was of 6.5/million
      inhabitants. The main etiologies were obstructive uropathy 18.3%, reflux
      nephropathy 15.1%, hemolytic uremic syndrome 14.4%, aplasia/dysplasia/hypoplasia
      13.8%, and focal segmental glomerulosclerosis 8.9%. From the patients on dialysis
      treatment, 62.3% were under hemodialysis, and only 37.7% on peritoneal dialysis.
      Live-donor sources accounted for 46.2 % of the transplants, with a 1-year
      patient's survival of 98.7% and a 1-year graft survival of 96.4 %, similar with
      both donors. CONCLUSION: The results obtained, even though they do not correspond
      to the total population affected and the monitoring is still insufficient,
      allowed us to have a profile of the chronic renal failure in our country.

PMID- 19107314
TI  - Patient-reported outcomes for tension-free vaginal tape-obturator in women
      treated with a previous anti-incontinence procedure.
AB  - Our purpose was to evaluate the outcome of a subset of patients that had a
      tension-free vaginal tape-obturator (TVT-O) placed following a previous anti
      incontinence procedure. We performed a retrospective analysis of 27 consecutive
      women who had a TVT-O placed from January 2004 to December 2007. Patients were
      given the Patient Global Impression of Improvement (PGI-I) questionnaire starting
      at the 3-month follow-up. Of 174 women who had a TVT-O placed, 27 (15.5%) had a
      prior failed anti-incontinence procedure or surgery performed. The mean age was
      63.8 years (range 43-87). Mean follow-up was 25.7 months (range 12-47 months).
      Based on the PGI-I, the overall success rate was 80% (20/25). In the properly
      selected patients with prior intervention for stress urinary incontinence (SUI),
      the success rate for TVT-O of 80% appears to be comparable to that of patients
      who never had a previous surgical or minimally invasive treatment for SUI.

PMID- 19107315
TI  - PCR-DGGE comparison of bacterial community structure in fresh and archived soils
      sampled along a Chihuahuan Desert elevational gradient.
AB  - The polymerase chain reaction coupled with denaturing gradient gel
      electrophoresis (PCR-DGGE) has been used widely to determine species richness and
      structure of microbial communities in a variety of environments. Researchers
      commonly archive soil samples after routine chemical or microbial analyses, and
      applying PCR-DGGE technology to these historical samples offers evaluation of
      long-term patterns in bacterial species richness and community structure that was
      not available with previous technology. However, use of PCR-DGGE to analyze
      microbial communities of archived soils has been largely unexplored. To evaluate
      the stability of DGGE patterns in archived soils in comparison with fresh soils,
      fresh and archived soils from five sites along an elevational gradient in the
      Chihuahuan Desert were compared using PCR-DGGE of 16S rDNA. DNA from all archived
      samples was extracted reliably, but DNA in archived soils collected from a closed
      canopy oak forest site could not be amplified. DNA extraction yields were lower
      for most archived soils, but minimal changes in bacterial species richness and
      structure due to archiving were noted in bacterial community profiles from four
      sites. Use of archived soils to determine long-term changes in bacterial
      community structure via PCR-DGGE appears to be a viable option for addressing
      microbial community dynamics for particular ecosystems or landscapes.

PMID- 19107316
TI  - Adrenal gland hypertrophy in a case of homolateral renal agenesis: case report
      with special emphasis on adrenal blood supply.
AB  - Hypertrophic suprarenal gland is an anomaly which can lead to serious
      complications during adrenalectomy under endoscopy because of abnormal veins of
      the retroperitoneum. The authors report a rare dissection of a male which
      presented with this anomaly in a case of homolateral renal agenesis, highlighting
      this left pseudorenal vein. No abnormality of the genital tract was found. The
      anatomic features, associated syndromes, implications for endoscopic surgery are
      outlined and embryologic considerations and discussed.

PMID- 19107317
TI  - The development of fetal pylorus during the fetal period.
AB  - OBJECTIVE: The objective of this study was to explore the localization of the
      pylorus, its macroscopic and microscopic development and relationship with
      neighboring structures. MATERIALS AND METHODS: The study is carried out on 160
      human fetuses aged between 9 and 40 weeks of gestation. Abdomen was divided into
      four quadrants by horizontal and vertical planes passing through the umbilicus.
      Topographical localization of the pylorus in reference to these quadrants and its
      distance were determined. Pylorus was divided into pre-pyloric, pyloric, and post
      pyloric regions. Starting from the pre-pyloric end, serial sections spanning
      whole pyloric part were obtained. Wall thickness, the thickness of the muscular
      coat were measured under light microscope using sections stained with hematoxylin
      eosin. Sections with the thickest muscular coat were considered as the region
      where pyloric sphincter was. FINDINGS: Pylorus was located in the right upper
      quadrant, on the median plane and in the left upper quadrant. There was a
      significant relation between the thickness of the muscular coat in the stomach,
      duodenum and the pyloric region and gestational age. In the region of the pyloric
      sphincter, the rate of increase in the thickness of the muscular coat was higher
      in the first and the first half of the second trimesters than term fetuses.
      CONCLUSION: We believe that data obtained in the present study will contribute to
      the assessment of development of the pyloric region in intra-uterine cases.

PMID- 19107318
TI  - Effects of diabetes and elevated glucose on nitrergic relaxations in the isolated
      duodenum of the rat.
AB  - Nitrergic relaxations of the isolated duodenum, induced by streptozotocin, were
      investigated in the experimental 8-week diabetes rat model. The effects of
      elevated glucose were also examined in the incubated duodenal muscles (in Krebs
      Henseleit solution containing 44 mM glucose for 6 h) taken from nondiabetic rats.
      The relaxations induced by electrical field stimulation (EFS) and nicotine were
      significantly reduced in diabetic rats compared with control rats. Incubating of
      duodenal tissues in medium containing elevated glucose revealed significantly
      impaired relaxations to EFS and nicotine compared to responses obtained after
      normal glucose incubation. However, the relaxant responses to sodium
      nitroprusside and papaverine were similar in all groups. Incubating in
      hyperosmolar solutions containing sucrose, the relaxant responses were not
      affected. In conclusion, impairment of NO-mediated relaxations in diabetes may be
      related to hyperglycemia. The alterations caused by elevated glucose are not due
      to a hyperosmotic effect because the same concentration of sucrose had no effect
      on the relaxations.

PMID- 19107319
TI  - Glycaemic profile characteristics and frequency of impaired awareness of
      hypoglycaemia in subjects with T1D and repeated hypoglycaemic events.
AB  - The aim of our study was to evaluate the frequency of hypoglycaemia unawareness
      and the continuous glucose profile in a group of subjects with Type 1 diabetes
      (T1D) with repeated non-severe/severe hypoglycaemia. Twenty patients (aged 35.2
      +/- 7.6 years, duration of disease 16.4 +/- 6.4 years) were included.
      Hypoglycaemia awareness was evaluated using questionnaires and after an acute
      induced hypoglycaemia. Glucose profile was studied using 72-h continuous glucose
      monitoring (CGM). All subjects were classified as having hypoglycaemia
      unawareness by questionnaires. Four patients displayed a "normal" signs/symptoms
      response to hypoglycaemia. The CGM revealed 18% of the measurements <70 mg/dl and
      this percentage was correlated with questionnaire score (r = 0.55, P < 0.035) and
      with the increase in the percentage of signs/symptoms during the induced
      hypoglycaemia (r = -0.57, P < 0.015). In patients exhibiting an "abnormal"
      response during hypoglycaemia, CGM values <70 mg/dl was higher (22.6 +/- 8.4%)
      than in those with a "normal" response (10.2 +/- 9.0%; P < 0.028). Summarising,
      in subjects with T1D and repeated hypoglycaemia the frequency of impaired
      awareness is substantially common. Its presence is related to a high proportion
      of ambulatory glycaemic profile below the desirable range.

PMID- 19107320
TI  - How often do we ask about erectile dysfunction in the diabetes review clinic?
      Development of a neuropathy screening tool.
AB  - Diabetic neuropathy is a significant complication of chronic diabetes. We wished
      to discover whether we were successfully identifying patients who had developed
      neuropathic problems. Specifically, Diabetologists are traditionally poor at
      asking about erectile dysfunction (ED) and patients themselves are not always
      forthcoming as it an embarrassing medical problem. We targeted all patients
      attending diabetes review clinics over a 4-month period in two hospitals and
      asked them to complete an anonymous, self-reported questionnaire after their
      consultation with the diabetologist or diabetes specialist nurse. Whilst most
      aspects of diabetic neuropathy are routinely screened for in the diabetes clinic
      we found that the neuropathic symptoms of both ED and gastroparesis were not
      commonly enquired about, and that erectile failure was found to be more prevalent
      than previously. Diabetologists need to be more thorough in their assessment of
      diabetic neuropathy. This is especially of import with regards to ED because we
      often shy away from enquiring into such a personal area and male patients rarely
      highlight the issue due to embarrassment. Our post consultation questionnaire has
      now been modified to form a useful preconsultation neuropathy screening tool and
      this is undergoing validation.

PMID- 19107321
TI  - Pulsed infrared light therapy does not increase nitric oxide concentration in the
      blood of patients with type 1 and type 2 diabetes mellitus.
AB  - The purpose of this study was to determine if NO blood concentrations increased
      acutely following an 8-week course of pulsed infrared light therapy (PILT) which
      could be linked to an improvement in peripheral protective sensation (PPS) in
      patients who have profound chronic diabetic peripheral neuropathy. A total of 22
      subjects with the diagnosis of type 1 (N = 2) or type 2 (N = 20) diabetes
      participated in the study. PILT was administered to one foot chosen at random
      with the other foot serving as a within-subject control (no treatment). Patients
      underwent 24 treatments (3 times/week, for 8 weeks) for 30 min per treatment.
      Venous blood samples were taken during the last 5 min of treatment from veins in
      the dorsum of the control and experimental feet and were later analyzed for NO
      concentration. Contrary to the popular supposition, PILT treatments actually
      resulted in a significantly (P < 0.05) decreased concentration of NO.
      Additionally, there were no significant differences between the treated and
      untreated feet. Since in individuals where PILT has significantly improved PPS,
      PILT did not stimulate an increased NO content in the blood, it appears that
      infrared light improves peripheral protective sensation in patients by a
      mechanism other than an increased NO production.

PMID- 19107322
TI  - Prevalence of diagnosed and undiagnosed diabetes mellitus and impaired fasting
      glucose in Sardinia.
AB  - We aimed at updating the prevalence of impaired fasting glucose (IFG) and of
      undiagnosed (UD) and diagnosed diabetes (DD) among the Sardinian population. The
      survey was carried out from 2002 to 2005 on 4.737 subjects aged 20-80+ years. IFG
      was diagnosed when blood glucose was 110-125 mg/dl; UD when it was >or=126 mg/dl
      in the absence of personal history of diabetes; DD when personal history was
      positive, irrespective of blood glucose value. Prevalence rates (%) were adjusted
      for age by direct method to the Italian 2001 population. IFG was diagnosed in 11%
      of the sample (9.88% in females and 12.24% in males); UD was found in 5.65% (5.20
      and 6.15%, females and males, respectively), DD in 8.72% (6.74 and 10.05%); and
      total diabetes (TD), i.e. the sum of UD + DD, was 14.37% (12.93 and 15.07%,
      females and males, respectively). In Sardinia, in about 5 years there was an
      increase of IFG (+61.8%), UD (+56.9%), DD (+55.7%), and TD (+57.9%). Thus
      Sardinia participates in the worldwide increase in prevalence of diabetes and its
      microvascular, macrovascular, and socioeconomic consequences.

PMID- 19107323
TI  - Victorivirus, a new genus of fungal viruses in the family Totiviridae.
AB  - The family Totiviridae comprises viruses with nonsegmented dsRNA genomes and
      isometric virions. A new genus, Victorivirus, has been approved for this family,
      named from the specific epithet of Helminthosporium victoriae, host of the type
      species, Helminthosporium victoriae virus 190S. Distinguishing characteristics of
      the 11 viruses so far assigned to this genus include infection of filamentous
      fungi, an apparently coupled termination-reinitiation mechanism for translating
      the RNA-dependent RNA polymerase as a separate product from the upstream capsid
      protein, and sequence-based phylogenetic grouping in a distinct clade from other
      family members.

PMID- 19107324
TI  - Microsatellite mutation rates in the eastern tiger salamander (Ambystoma tigrinum
      tigrinum) differ 10-fold across loci.
AB  - Microsatellites are commonly used for mapping and population genetics because of
      their high heterozygosities and allelic variability (i.e., polymorphism).
      Microsatellite markers are generally more polymorphic than other types of
      molecular markers such as allozymes or SNPs because the insertions/deletions that
      give rise to microsatellite variability are relatively common compared to
      nucleotide substitutions. Nevertheless, direct evidence of microsatellite
      mutation rates (MMRs) is lacking in most vertebrate groups despite the importance
      of such estimates to key population parameters (e.g., genetic differentiation or
      theta = 4N (e)micro). Herein, we present empirical data on MMRs in eastern tiger
      salamanders (Ambystoma tigrinum tigrinum). We conducted captive breeding trials
      and genotyped over 1,000 offspring at a suite of microsatellite loci. These data
      on 7,906 allele transfers provide the first direct estimates of MMRs in
      amphibians, and they illustrate that MMRs can vary by more than an order of
      magnitude across loci within a given species (one locus had ten mutations whereas
      the others had none).

PMID- 19107325
TI  - Circulating proinflammatory cytokines and N-terminal pro-brain natriuretic
      peptide significantly decrease with recovery of left ventricular function in
      patients with dilated cardiomyopathy.
AB  - BACKGROUND: Increased levels of TNF-alpha, IL-6, their soluble receptors, and NT
      proBNP have been observed in patients with dilated cardiomyopathy (DCM). In the
      present study, we assessed the possible involvement of proinflammatory cytokines
      and their soluble receptors with and without recovery of LV function in DCM
      patients. METHODS AND RESULTS: Forty patients with DCM were enrolled and divided
      into two groups: Group I consisted of DCM patients (n = 30) whose left
      ventricular ejection fraction (LVEF) had not recovered on follow up and Group II
      comprised DCM patients (n = 10) whose LVEF had recovered. Ten healthy subjects
      were included as controls (Group III). TNF-alpha, IL-6,TNFR1, TNFRII, gp130, and
      NT-proBNP levels were significantly increased in Group I and were significantly
      lower in patients with LVEF recovery as compared to those without recovery of
      LVEF (P < 0.05). CONCLUSION: Circulating TNF-alpha, IL-6, and NT-proBNP appear to
      correlate with the LV function recovery of patients with DCM and could be used as
      prognostic biomarkers.

PMID- 19107326
TI  - Up regulation of the GRP-78 and GADD-153 and down regulation of Bcl-2 proteins in
      primary glomerular diseases: a possible involvement of the ER stress pathway in
      glomerulonephritis.
AB  - The role of endoplasmic reticulum (ER) stress in kidney diseases is not well
      elucidated. Fifty patients with primary glomerular diseases (PGD): minimal change
      disease (MCD), focal segmental glomerulosclerosis (FSGS), membranous
      glomerulonephritis (MGN), membranoproliferative glomerulonephritis (MPGN), and
      crescentic glomerulonephritis, n = 10 (each group) were enrolled. MCD, FSGS, and
      MGN patients were sub-grouped as nonproliferative glomerulonephritis (NPGN) and
      MPGN, RPGN as proliferative glomerulonephritis (PGN). Glucose regulated proteins
      (GRP-78), growth arrest and DNA damage inducible proteins (GADD-153), and Bcl-2
      protein expression was analyzed by Western blotting, immunofluorescence and
      immunohistochemistry in the kidney biopsy. Up regulation of GADD-153, GRP-78,
      with more pronounced expression in PGN vs. NPGN (P < 0.05) and down regulation of
      Bcl-2 proteins was observed in the GN (PGD excluding MCD) as compared to MCD (P <
      0.05). Our results suggest that renal injury in PGD is associated with ER stress
      and ER stress may be involved in the rapid progression of PGN to renal failure.

PMID- 19107327
TI  - ADSCs differentiated into cardiomyocytes in cardiac microenvironment.
AB  - The microenvironment plays a critical role in directing the progression of stem
      cells into differentiated cells. So we investigated the role that cardiac
      microenvironment plays in directing this differentiation process. Adipose tissue
      derived stem cells (ADSCs) were cultured with cardiomyocytes directly ("co
      culture directly") or by cell culture insert ("co-culture indirectly"). For co
      culture indirectly, differentiated ADSCs were collected and identified. For co
      culture directly, ADSCs were labeled with carboxyfluorescein succinimidyl ester
      (CFSE), Fluorescence-activated cell sorting was used to extract and examine the
      differentiated ADSCs. The ultrastructure and the expression of cardiac specific
      proteins and genes were analyzed by SEM, TEM, western blotting, and RT-PCR,
      respectively. Differentiated ADSCs experienced the co-culture presented cardiac
      ultrastructure and expressed cardiac specific genes and proteins, and the
      fractions of ADSCs expressing these markers by co-culture directly were higher
      than those of co-culture indirectly. These data indicate that in addition to
      soluble signaling molecules, direct cell-to-cell contact is obligatory in
      relaying the external cues of the microenvironment controlling the
      differentiation of ADSCs to cardiomyocytes.

PMID- 19107328
TI  - The effect of age and gender on Al, B, Ba, Ca, Cu, Fe, K, Li, Mg, Mn, Na, P, S,
      Sr, V, and Zn contents in rib bone of healthy humans.
AB  - The effect of age and gender on major, minor, and trace element contents in the
      intact rib bone of 80 relatively healthy 15-55-year-old women and men was
      investigated. Contents or upper limit of contents of 16 chemical elements in the
      rib bone were determined by inductively coupled plasma atomic emission
      spectrometry (ICP-AES). Mean values (M +/- SEpsilonMu) for the mass fraction of
      Ba, Ca, Cu, Fe, K, Li, Mg, Na, P, S, Sr, and Zn (milligram per kilogram of dry
      bone) were as follows: 2.54 +/- 0.16, 171,400 +/- 4,050, 1.35 +/- 0.22, 140 +/-
      11, 1,874 +/- 71, 0.049 +/- 0.011, 2,139 +/- 38, 5,378 +/- 88, 75,140 +/- 1,660,
      1,881 +/- 51, 291 +/- 20, and 92.8 +/- 1.5, respectively. The upper limits of
      contents of Al, B, Mn, and V were <7.20, <0.65, <0.36, and <0.03, respectively.
      Statistically significant tendency for the Ca, Mg, and P content to decrease with
      age was found in the human rib bone, regardless of gender. The mass fraction of
      Fe in the male rib bone increases with age. It was shown that higher Ca, Mg, Na,
      P, and Sr mass fractions as well as lower Fe content were typical of female ribs
      as compared to those in male ribs.

PMID- 19107329
TI  - The association between arsenic and children's intelligence: a meta-analysis.
AB  - This present study was undertaken to investigate whether arsenic exposure
      increases the risk of children's low intelligence quotient (IQ) in China.
      MEDLINE, SCI, CNKI, and CBM search were organized for all documents published, in
      English and Chinese, between 1988 and 2008 using the following keywords: arsenic,
      intelligence, and IQ. As a result, four cross-sectional studies that assessed the
      development of low IQ in children who had been exposed to arsenic earlier in
      their life were included in this study. The summary weighted mean difference of
      IQ was calculated in this meta-analyses, when arsenicosis areas or slight
      arsenicosis areas were compared with non-arsenicosis areas; it is -6.85 (95%
      confidence interval [CI] = -8.30 to -5.41; p < 0.01, using a fixed effect model)
      and -6.54 (95%CI = -8.93 to -4.15; p < 0.01, using a random effect model), which
      means that children who live in an arsenicosis area or a slight arsenicosis area
      have lower IQ than those who live in a non-arsenicosis area, and there may be a
      strong association between arsenic and children's intelligence.

PMID- 19107330
TI  - Primary MALT lymphoma of the upper lip mucosa: an exceptionally rare
      localisation.

PMID- 19107331
TI  - Cord blood transplantation using minimum conditioning regimens for patients with
      hematologic malignancies complicated by severe infections.
AB  - Patients with severe infections are thought to be ineligible for cord blood stem
      cell transplantation (CBT) because the conventional 5-6 day-conditioning regimens
      potentially makes them susceptible to fatal infections by the time neutrophil
      engraftment occurs. Two patients were treated with minimum conditioning regimens
      consisting of 30 mg/m(2) fludarabin (Flu) and 2 g/m(2) cyclophosphamide (CY) on
      day-1 and total body irradiation (TBI) of 2 or 4 Gy on day -1 or 0 followed by
      single unit CBT. The reasons for adopting such weak regimen were febrile
      neutropenia due to the rejection of the first cord blood (CB) graft given to a
      patient with follicular lymphoma resistant to chemotherapy and pulmonary
      aspergillosis in another patient with AML who relapsed after CBT. The AML patient
      received 40 mg/m(2) of melphalan on day-2 to reduce the leukemia burden. Both
      patients achieved 100% donor chimerism by day 19 and day 20 after CBT without an
      apparent exacerbation of the infections and remained in remission at 23 and 18
      months after the CBT. These findings suggest that the 1-2 day regimens excluding
      antihuman thymocyte globulin may be sufficiently potent to ensure engraftment of
      CB in immunocompromised patients and safely administered even when patients are
      complicated by active infections.

PMID- 19107332
TI  - Hepatitis B virus reactivation during combined therapy with deferiprone and
      desferioxamine in a hepatitis B surface antigen thalassemic carrier.
AB  - In this report we firstly describe a case of reactivation of hepatitis B virus
      (HBV) replication occurred in a patient affected by Thalassemia major which
      underwent a combined chelation therapy with desferioxamine (DFO) and deferiprone
      (DFP). Clinical symptom and increase in alanine aminotransferase (ALT) level were
      detected when the prescription of DFO (30 mg/kg) was increased from 3 to 5
      days/week; a raise in HBV-DNA levels of greater than or equal to tenfold compared
      with baseline was thereafter detected. Diagnosis was troublesome because
      increasing ALT levels, first suggested toxicity to DFP administration. However,
      HBV reactivation in our patient cannot be definitively attributed to combined
      regimen administration: the patient was on regular transfusion therapy and either
      coincidental further infection or spontaneous reactivation of HBV could not be
      completely ruled out. Furthermore, a background of immunologic abnormalities had
      been previously reported in thalassemia and postulated to be secondary to iron
      overload or DFO therapy itself.

PMID- 19107333
TI  - Molecular targeting therapy for pancreatic cancer: current knowledge and
      perspectives from bench to bedside.
AB  - Current medical interventions for pancreatic cancer are insufficient. Recent
      molecular investigations have elucidated complex genetic mechanisms of cancer
      that especially involve multiple signal transduction pathways; this enables us to
      develop molecular medicines targeting specific genetic molecules in the pathways.
      These molecular medicines seem to promise clues for curing cancers, including
      pancreatic cancer. This review describes current knowledge and perspectives
      regarding the development of molecular medicines for pancreatic cancer by
      focusing on growth factor receptor systems and three major signal transduction
      pathways: the RAS-MAPK, PI3K-AKT-mTOR, and hedgehog pathways.

PMID- 19107334
TI  - Highly stomach-selective gene transfer following gastric serosal surface
      instillation of naked plasmid DNA in rats.
AB  - BACKGROUND: The purpose of this study was to achieve stomach-selective gene
      transfer in rats by our simple and novel administration method, which is gastric
      serosal surface instillation of naked plasmid DNA (pDNA). METHODS: Naked pDNA
      encoding firefly luciferase as a reporter gene was instilled onto the gastric
      serosal surface in male Wistar rats. As controls, we performed intraperitoneal,
      intragastric and intravenous administration of naked pDNA. At appropriate time
      intervals, we measured luciferase activities in the stomach and other tissues.
      RESULTS: Gene expression in the stomach 6 h after gastric serosal surface
      instillation of naked pDNA (5 microg) was significantly higher than that after
      using other administration methods. The present study is the first report on
      stomach-selective gene transfer following instillation of naked pDNA onto the
      gastric serosal surface in rats. Also, the gene expression level in the stomach 6
      h after gastric serosal surface instillation of naked pDNA was markedly higher
      than that in other tissues. In a dose-dependent study, the gene expression level
      was saturated over 5 microg. Gene expression in the stomach was detected 3 h
      after gastric serosal surface instillation of naked pDNA. The gene expression
      level peaked 12-24 h after instillation of naked pDNA, then decreased to a level
      similar to 3 h at 48 h. CONCLUSIONS: Gastric serosal surface in stillation of
      naked pDNA can be a highly stomach-selective gene transfer method in rats.

PMID- 19107335
TI  - The demographic characteristics and health-related quality of life in a large
      cohort of reflux esophagitis patients in Japan with reference to the effect of
      lansoprazole: the REQUEST study.
AB  - BACKGROUND: Patients with reflux esophagitis (RE) in Western countries have
      impaired health-related quality of life (HRQOL). However, few data are available
      concerning HRQOL in Asian patients with RE. AIM: To determine the demographic
      characteristics, HRQOL, and the impact of lansoprazole treatment in a large
      cohort of RE patients in Japan. METHODS: Patients with RE were enrolled.
      Lansoprazole was administered for 8 weeks and HRQOL assessed using the SF-8 and a
      newly developed questionnaire for RE-specific HRQOL (RESQ) at baseline and after
      4 and 8 weeks of treatment. RESULTS: Among enrolled patients, 2320 patients with
      the Los Angeles classification grade A to D esophagitis at enrollment to the
      study were analyzed. A higher proportion of older women was observed (in the
      group of patients aged >or=60 years, 61.3% were women). Prevalence of obesity was
      4.7%. At baseline, HRQOL scores of RE patients were well below the mean for the
      Japanese general population in all domains of the SF-8. After 8 weeks of
      treatment with lansoprazole, these scores significantly improved to the levels of
      the general population (P < 0.01). Scores of RESQ also significantly improved (P
      < 0.01). CONCLUSIONS: Demographically, RE patients in Japan differ from those in
      Western countries with an increased proportion in older women and lower
      prevalence of obesity. RE has a marked negative impact on HRQOL, which is
      significantly improved by treatment with lansoprazole.

PMID- 19107336
TI  - Barrett's esophagus in Japanese patients: its prevalence, form, and elongation.
AB  - BACKGROUND: Barrett's esophagus is a well-known acquired condition resulting from
      gastroesophageal reflux disease (GERD). However, it is still unknown whether
      Barrett's esophagus develops gradually over time in patients with GERD. To
      address this issue, we investigated the change in the prevalence and length of
      short-segment Barrett's esophagus (SSBE) over time. METHODS: From January 2005 to
      March 2007, we enrolled 5338 patients who received upper gastrointestinal
      endoscopy. Prevalence and length of endoscopically identified SSBE were evaluated
      within groups divided on the basis of 10-year age intervals. The factors possibly
      influencing SSBE length such as symptoms, antacid use, and endoscopic findings
      were also evaluated. Additionally, the length change in 236 patients with
      histologically confirmed Barrett's esophagus was evaluated over a 2-year follow
      up. RESULTS: Of the 5338 enrolled patients, 1997 had SSBE. The prevalence of
      endoscopically identified SSBE was significantly higher and its length was
      significantly longer in elderly patients. Multiple regression analysis showed
      that age, presence of reflux esophagitis, reflux symptoms, and hiatal hernia were
      positively correlated with SSBE length. Analysis of the 2-year follow-up study of
      histologically confirmed SSBE revealed significant extension of Barrett's length
      in 28.0% of 236 patients. Presence of reflux symptoms and hiatal hernia were
      identified as positive predictors and proton pump inhibitor administration as a
      negative predictor of SSBE elongation. CONCLUSIONS: Positive predictors for the
      extension of SSBE were presence of hiatal hernia and reflux symptoms, but not
      age.

PMID- 19107337
TI  - Real-time evaluation of dyspeptic symptoms and gastric motility induced by
      duodenal acidification using noninvasive transnasal endoscopy.
AB  - BACKGROUND: Although different pathophysiological mechanisms have been suggested
      to be involved in functional dyspepsia, a practical method to clarify them has
      not been established. The aim of this study was to evaluate dyspeptic symptoms
      and gastric motility induced by duodenal acidification using transnasal
      endoscopy. METHODS: Fourteen healthy volunteers (mean age, 32 years) were
      enrolled. Transnasal endoscopy was performed on all fasting volunteers. Dyspeptic
      symptoms and antral contractions were evaluated before and after duodenal
      infusions of pure water (20 ml/min for 5 min) and acid (0.1 N HCl, 20 ml/min for
      5 min). The severity of various symptoms was assessed by each subject using a 10
      cm visual analog scale every 2 min. The maximum severity scale was calculated as
      the mean of the individual maximum values. The motility number was defined as the
      mean number of antral contractions in 1 min. RESULTS: The maximum severity score
      for a heavy feeling in the stomach and other symptoms significantly increased
      after the acid infusion compared with after the pure water infusion. During pure
      water infusion, there were no changes in the motility number. On the other hand,
      the motility number significantly decreased after duodenal acidification (before
      vs. after, 2.93 +/- 0.12 times vs. 1.11 +/- 0.23 times, P < 0.0001). CONCLUSIONS:
      Duodenal acid exposure induces dyspeptic symptoms and inhibits antral motility.
      Transnasal endoscopy enabled us to evaluate both dyspeptic symptoms and gastric
      motility simultaneously.

PMID- 19107339
TI  - Precise histological evaluation of liver biopsy specimen is indispensable for
      diagnosis and treatment of acute-onset autoimmune hepatitis.
AB  - BACKGROUND: The diagnosis of acute-onset autoimmune hepatitis (AIH) has been
      difficult because patients do not always show clinicopathological features
      typical of AIH. We examined the important requirements for a definitive diagnosis
      of acute-onset AIH. METHODS: Clinical, biochemical, and pathological features of
      18 acute-onset AIH patients (16 women, 2 men; mean age, 54.3 +/- 12.3 years) with
      no history of liver disease and no signs of chronicity were examined. RESULTS:
      Mean ALT was 679 +/- 431 IU/l, and mean T-Bil was 2.4 +/- 2.9 mg/dl. Mean IgG was
      1801 +/- 446 mg/dl, with 7 patients (39%) showing normal levels. Antinuclear
      antibody was <or=1: 40 in 7 (39%). Liver histology showed severe activity in 17
      (94%) of the patients and severe acute hepatitis in 7 (39%). Centrizonal necrosis
      and plasma cell accumulation were characteristic for acute-onset AIH. AIH score
      ranged from 7 to 18 (13.2 +/- 3.8) before treatment. All patients were diagnosed
      and treated early and responded completely to therapy. CONCLUSIONS: Histological
      examination of the liver is necessary for early diagnosis of acute-onset AIH.
      Moreover, we should evaluate liver biopsy specimens precisely and should be ready
      for a timely initiation of corticosteroid therapy to improve the prognosis.

PMID- 19107338
TI  - Association of a genetic polymorphism in ectonucleotide
      pyrophosphatase/phosphodiesterase 1 with hepatitis C virus infection and
      hepatitis C virus core antigen levels in subjects in a hyperendemic area of
      Japan.
AB  - BACKGROUND: The clinical course of chronic hepatitis C virus (HCV) infection is
      strongly associated with insulin resistance and obesity. The K121Q polymorphism
      in the ectonucleotide pyrophosphatase/phosphodiesterase (ENPP)-1 gene and the
      rs7566605 genotype located near insulin-induced gene 2 have been shown to be
      associated with insulin resistance and obesity. This study examined whether the
      K121Q polymorphism in ENPP1 or the rs7566605 genotype is associated with the
      clinical course of HCV infection. METHODS: The relationships between the clinical
      characteristics of 469 anti-HCV antibody-seropositive subjects (353 were positive
      for HCV core antigen or RNA, whereas 116 were negative for HCV RNA) and the
      polymorphisms were analyzed. RESULTS: No significant differences in body mass
      index, plasma glucose level, serum insulin level, and other biochemical markers
      were observed between subgroups of subjects with different genotypes at the K121Q
      polymorphism or rs7566605. The frequency of the homozygous wild-type genotype at
      K121Q in HCV carriers, however, was significantly higher than that in subjects
      who were negative for HCV RNA (84.5% vs. 75.9%; P < 0.05). Moreover, in HCV
      carriers, HCV core antigen levels in subjects homozygous for the wild-type
      genotype at K121Q were significantly higher than in heterozygous carriers of
      K121Q (5358 fmol/l vs. 4002 fmol/l; P = 0.04). In contrast, the rs7566605
      genotype was not associated with hepatitis C viremia or with the HCV core antigen
      level. CONCLUSIONS: The K121Q variant of ENPP1 may be associated with hepatitis C
      viremia and core antigen levels in HCV carriers.

PMID- 19107340
TI  - Microvessel density correlates with lymph node metastases and prognosis in hilar
      cholangiocarcinoma.
AB  - BACKGROUND: Neovascularization was shown to be critically involved in the
      progression of multiple cancers, and treatment approaches targeting tumor
      associated neovascularization provide convincing results in recent years in some
      tumor entities. However, little is known about the tumor-associated
      neovascularization in hilar cholangiocarcinoma. The present study was conducted
      to analyze tumor-associated neovascularization in hilar cholangiocarcinoma and to
      determine its influence on tumor growth, metastasis, recurrence, and prognosis.
      METHODS: We analyzed tissue specimens of hilar cholangiocarcinoma (n = 60) by
      immunohistochemistry using the endothelial-specific antibody CD31 and
      subsequently quantified the microvessel density (MVD). The MVD was correlated
      with clinicopathological characteristics and recurrence pattern of the tumors as
      well as survival of patients. RESULTS: Hilar cholangiocarcinoma revealed a high
      degree of vascularization, with a calculated mean MVD of 28.1 +/- 14.5 vessels.
      Tumors with a high MVD had a significant higher incidence of lymph node
      involvement (P = 0.009) and local recurrence (P < 0.001). Furthermore, a high MVD
      was identified to be a significant overall survival disadvantage (3-year, 28% vs.
      93%; 5-year, 8% vs. 78%; P < 0.001) as well as disease-free survival disadvantage
      (3-year, 7% vs. 88%, 5-year, 7% vs. 72%; P < 0.001), with MVD representing an
      independent prognostic factor for survival. CONCLUSIONS: Neovascularization is
      associated with nodal spread as well as local recurrence and serves as an
      independent prognostic factor for survival after curative resection of hilar
      cholangiocarcinoma. Therefore, tumor-associated neovascularization seems to be
      critically involved in the progression of this tumor entity. In addition,
      neovascularization may represent a potential target in he development of new
      therapeutic approaches in hilar cholangiocarcinoma.

PMID- 19107341
TI  - Etiology of non-B non-C hepatocellular carcinoma in the eastern district of
      Tokyo.
AB  - BACKGROUND: This study was carried out to clarify the carcinogenic factors
      associated with nonviral hepatocellular carcinoma (HCC). METHODS: A total of 320
      HCC patients diagnosed and treated from January 2000 to December 2006 were
      enrolled. The clinical characteristics of non-B non-C HCC patients were examined
      to determine possible carcinogenic factors. RESULTS: Of 320 HCC patients, 64 were
      classified as having non-B non-C HCC. The proportion of non-B non-C HCC increased
      from 17.8% in 2000 to 28.6% in 2006. Non-B non-C HCC patients had a significantly
      higher rate of early stage cirrhosis (Child-Pugh classification) than viral HCC
      patients. Significantly fewer non-B non-C HCC patients had periodic intensive
      medical assessments than viral HCC patients. Forty-five non-B non-C HCC patients
      were habitual alcohol drinkers, ten had nonalcoholic fatty liver disease (NAFLD),
      and seven had no apparent etiology. In habitual drinkers, the stage of underlying
      liver disease varied widely, while most NAFLD patients had early stage cirrhosis.
      On the other hand, more than half of the patients with HCC of undetermined
      etiology had noncirrhotic liver disease. Among habitual drinkers, the underlying
      liver disease was more progressive, and the T stage was more advanced in those
      with high daily alcohol intake than in those with low daily alcohol intake.
      Periodic intensive medical assessments were crucial for detecting early stage
      HCC. CONCLUSIONS: Alcohol consumption and NAFLD may be important etiological
      factors in non-B non-C HCC. Periodic medical assessments for all patients with
      non-B non-C cirrhosis are crucial for early diagnosis and curative therapy.

PMID- 19107342
TI  - Clinicopathological features, background liver disease, and survival analysis of
      HCV-positive patients with hepatocellular carcinoma: differences between young
      and elderly patients.
AB  - BACKGROUND: The aim of this retrospective study was to determine the incidence
      and characteristics of hepatocellular carcinoma (HCC) in hepatitis C virus (HCV)
      antibody-positive elderly patients with chronic hepatitis without cirrhosis.
      METHODS: The study included 65 patients who developed HCC at >or=75 years of age
      and who received their first HCC therapy at Toranomon Hospital between 1985 and
      2005. Their clinicopathological and laboratory data were analyzed and compared
      with those of 33 patients who developed HCC at <or=50 years of age during the
      same period. RESULTS: The ratio of women patients in the elderly group (M: F =
      1.1: 1) was higher than in the younger group (M: F = 5.6: 1). Also, patients in
      the elderly group had better liver function and prothrombin activity (P = 0.001),
      and lower total bilirubin (P = 0.002) than the young group. Only 11 of 65 elderly
      patients were diagnosed with liver cirrhosis by biopsy or peritoneoscopy before
      or at the time of development of HCC. Based on a discriminate score using gamma
      globulin, hyaluronate level, platelet count, and sex, 27 (41.5%) elderly patients
      were considered to have chronic hepatitis, compared with six of 33 (18.1%)
      patients in the young group (P = 0.025). There were no differences in tumor
      number or size or tumor markers between the two groups. Survival rate was higher
      in the younger patients (P = 0.002), who were more likely to receive radical
      treatment. CONCLUSIONS: Our results showed distinct differences in HCV-related
      HCC between elderly and young patients and suggested that elderly patients
      (especially women) could develop HCC even when liver histology shows chronic
      hepatitis and lack of cirrhosis.

PMID- 19107343
TI  - Beneficial effects of living-donor liver transplantation on esophageal varices.
AB  - BACKGROUND: Liver transplantation (LT) is known to improve bleeding esophageal
      varices (EVs) and portal hypertension. However, many issues related to EVs after
      LT remain unresolved, such as whether LT reduces blood supply to EVs, improves
      the diameter of unruptured EVs, or improves or worsens EVs. The aim of this
      retrospective study was to determine the effects of living-donor liver
      transplantation (LDLT) in patients with hepatic failure on EVs and inflow vessels
      to EVs and the factors associated with deterioration of EVs after LDLT. METHODS:
      The study subjects were 35 patients with cirrhosis who underwent LDLT. Endoscopy
      and multidetector helical computed tomography (MDCT) were performed before and
      after LDLT. The diameter of the inflow vessel of EVs was measured by MDCT before
      and after LDLT, together with the LDLT-related reduction rate of the diameter of
      the gastric vein (RRGV). RESULTS: Endoscopic examination showed improvement of
      EVs in 30 of 35 (86%) patients. RRGV improved in 17/35 (49%) patients, did not
      change in 13/35 (37%), and deteriorated in 5/35 (14%). The cause of RRGV
      deterioration seemed to be either the complication of portal vein or graft
      failure. In patients examined endoscopically at >1 year after LDLT, improvement
      of EVs was associated with significant changes in the rate of reduction of the
      major inflow vessel diameter and Child-Pugh score, compared with those who showed
      no improvement. CONCLUSIONS: LDLT results in improvement of EVs. EVs improved in
      86% of the patients. Measurement of RRGV with MDCT is a good tool for prediction
      of EV improvement after LDLT.

PMID- 19107344
TI  - The Munich Fission Neutron Therapy Facility MEDAPP at the research reactor FRM
      II.
AB  - PURPOSE: At the new research reactor FRM II of the Technical University of Munich
      (TUM), the facility for Medical Applications (MEDAPP) was installed where fast
      neutrons are available as a beam for medical use. MATERIAL AND METHODS: Thermal
      neutrons induce fission in a pair of uranium converter plates and generate fast
      neutrons which are guided to the patient by a beam tube. The maximum opening of
      the multi leaf collimator (MLC) is 30x20 cm2 WxH. The beam is characterized by
      neutron-photon mixed beam phantom dosimetry. Specific safety measures are
      outlined. RESULTS: The neutron and gamma dose rates are 0.52 Gy/min and 0.20
      Gy/min, respectively, in 2 cm depth of a water phantom. The half maximum depth of
      the neutron dose rate in water is 5.4 cm (mean neutron energy 1.9+/-0.1 MeV).
      Conformity with the European Medical Devices Directive (MDD) 93/42/EEG, was
      proven so that MEDAPP has a CE mark and since February 2007 also the license for
      clinical operation. CONCLUSION: The clinical neutron irradiations of malignant
      tumors, which were performed at the former research reactor FRM until 2000, can
      be continued at FRM II under improved conditions. First patients were irradiated
      in June 2007.

PMID- 19107345
TI  - Acute neurocognitive impairment during cranial radiation therapy in patients with
      intracranial tumors.
AB  - BACKGROUND AND PURPOSE: The objective of the current study was to evaluate the
      acute effects of cranial radiation therapy (CNS-RT) using different radiation
      doses (0, 1.8, 2, 3, >or=20 Gy) on cognitive function with special emphasis on
      memory. We assessed patients with and without intracranial tumors to distinguish
      between direct and indirect radiation effects on brain tissue. MATERIALS AND
      METHODS: Eighty-two patients were evaluated with neuropsychological testing
      before and acutely after radiotherapy (RT). Sixty-four patients received RT to
      the brain (55 with, 9 without intracranial tumor). Eighteen patients treated with
      RT to the breast served as controls. RESULTS: Patients with intracranial tumor
      demonstrated attention (19-38th percentile) and verbal memory scores (34-46th
      percentile) below the population average at baseline. The average Verbal Memory
      score was significantly different between patients with intracranial tumor and
      controls both at baseline (38th vs. 58th percentile) and after irradiation (27th
      vs. 52th percentile). Patients with preexisting peritumoral edema performed worse
      than patients without edema and controls. Radiation dose-related deficits were
      seen for working memory performance in patients with intracranial tumor.
      CONCLUSION: Our data indicate no measurable impairment of cognitive functioning
      acutely after prophylactic cranial irradiation. Patients with intracranial tumor
      show a deterioration of almost all memory functions with a dose-dependent
      impairment in working memory. Patients with preexisting peritumoral brain edema
      show the strongest deterioration.

PMID- 19107346
TI  - Comparison of stereotactic radiosurgery (SRS) alone and whole brain radiotherapy
      (WBRT) plus a stereotactic boost (WBRT+SRS) for one to three brain metastases.
AB  - BACKGROUND: The best available treatment of patients with one to three brain
      metastases is still unclear. This study compared the results of stereotactic
      radiosurgery (SRS) alone and whole brain radiotherapy (WBRT) plus SRS (WBRT+SRS).
      PATIENTS AND METHODS: Survival (OS), intracerebral control (IC), and local
      control of treated metastases (LC) were retrospectively analyzed in 144 patients
      receiving SRS alone (n=93) or WBRT+SRS (n=51). Eight additional potential
      prognostic factors were evaluated: age, gender, Eastern Cooperative Oncology
      Group performance score (ECOG-PS), tumor type, number of brain metastases,
      extracerebral metastases, recursive partitioning analysis (RPA) class, and
      interval from tumor diagnosis to irradiation. Subgroup analyses were performed
      for RPA class I and II patients. RESULTS: 1-year-OS was 53% after SRS and 56%
      after WBRT+SRS (p=0.24). 1-year-IC rates were 51% and 66% (p=0.015),
      respectively. 1-year-LC rates were 66% and 87% (p=0.003), respectively. On
      multivariate analyses, OS was associated with age (p=0.004), ECOG-PS (p=0.005),
      extracerebral metastases (p<0.001), RPA class (p<0.001), and interval from tumor
      diagnosis to irradiation (p<0.001). IC was associated with interval from tumor
      diagnosis to irradiation (p=0.004) and almost with treatment (p=0.09), and LC
      with treatment (p=0.026) and almost with interval (p=0.08). The results of the
      subgroup analyses were similar to those of the entire cohort. The increase in IC
      was stronger in RPA class I patients. CONCLUSION: WBRT+SRS resulted in better IC
      and LC but not better OS than SRS alone. Because also IC and LC are important end
      points, additional WBRT appears justified in patients with one to three brain
      metastases, in particular in RPA class I patients.

PMID- 19107347
TI  - A strategy for the use of image-guided radiotherapy (IGRT) on linear accelerators
      and its impact on treatment margins for prostate cancer patients.
AB  - BACKGROUND AND PURPOSE: In external beam radiotherapy of prostate cancer, the
      consideration of various systematic error types leads to wide treatment margins
      compromising normal tissue tolerance. We investigated if systematic set-up errors
      can be reduced by a set of initial image-guided radiotherapy (IGRT) sessions.
      PATIENTS AND METHODS: 27 patients received daily IGRT resulting in a set of 882
      cone-beam computed tomographies (CBCTs). After matching to bony structures, we
      analyzed the dimensions of remaining systematic errors from zero up to six
      initial IGRT sessions and aimed at a restriction of daily IGRT for 10% of all
      patients. For threshold definition, we determined the standard deviations (SD) of
      the shift corrections and selected patients out of this range for daily image
      guidance. To calculate total treatment margins, we demanded for a cumulative
      clinical target volume (CTV) coverage of at least 95% of the specified dose in
      90% of all patients. RESULTS: The gain of accuracy was largest during the first
      three IGRTs. In order to match precision and workload criteria, thresholds for
      the SD of the corrections of 3.5 mm, 2.0 mm and 4.5 mm in the left-right (L-R),
      cranial-caudal (C-C), and anterior-posterior (A-P) direction, respectively, were
      identified. Including all other error types, the total margins added to the CTV
      amounted to 8.6 mm in L-R, 10.4 mm in C-C, and 14.4 mm in A-P direction.
      CONCLUSION: Only initially performed IGRT might be helpful for eliminating gross
      systematic errors especially after virtual simulation. However, even with daily
      IGRT performance, a substantial PTV margin reduction is only achievable by
      matching internal markers instead of bony anatomical structures.

PMID- 19107348
TI  - Intra-fractional uncertainties in image-guided intensity-modulated radiotherapy
      (IMRT) of prostate cancer.
AB  - PURPOSE: To evaluate intra-fractional uncertainties during intensity-modulated
      radiotherapy (IMRT) of prostate cancer. PATIENTS AND METHODS: During IMRT of 21
      consecutive patients, kilovolt (kV) cone-beam computed tomography (CBCT) images
      were acquired prior to and immediately after treatment: a total of 252 treatment
      fractions with 504 CBCT studies were basis of this analysis. The prostate
      position in anterior-posterior (AP) direction was determined using contour
      matching; patient set-up based on the pelvic bony anatomy was evaluated using
      automatic image registration. Internal variability of the prostate position was
      the difference between absolute prostate and patient position errors. Intra
      fractional changes of prostate position, patient position, rectal distension in
      AP direction and bladder volume were analyzed. RESULTS: With a median treatment
      time of 16 min, intra-fractional drifts of the prostate were >5 mm in 12% of all
      fractions and a margin of 6 mm was calculated for compensation of this
      uncertainty. Mobility of the prostate was independent from the bony anatomy with
      poor correlation between absolute prostate motion and motion of the bony anatomy
      (R2=0.24). A systematic increase of bladder filling by 41 ccm on average was
      observed; however, these changes did not influence the prostate position. Small
      variations of the prostate position occurred independently from intra-fractional
      changes of the rectal distension; a weak correlation between large internal
      prostate motion and changes of the rectal volume was observed (R2=0.55).
      CONCLUSION: Clinically significant intra-fractional changes of the prostate
      position were observed and margins of 6 mm were calculated for this intra
      fractional uncertainty. Repeated or continuous verification of the prostate
      position may allow further margin reduction.

PMID- 19107349
TI  - Reduced rectal toxicity with ultrasound-based image guided radiotherapy using BAT
      (B-mode acquisition and targeting system) for prostate cancer.
AB  - PURPOSE: To evaluate the effect of image guided radiotherapy with stereotactic
      ultrasound BAT (B-mode acquisition and targeting system) on rectal toxicity in
      conformal radiotherapy of prostate cancer. PATIENTS AND METHODS: 42 sequential
      patients with prostate cancer undergoing radiotherapy before and after the
      introduction of BAT were included. Planning computed tomography (CT) was
      performed with empty rectum and moderately filled bladder. The planning target
      volume (PTV) included the prostate and seminal vesicles with a safety margin of
      1.5 cm in anterior and lateral direction. In posterior direction the anterior 1/3
      of the rectum circumference were included. Total dose was 66 Gy and a boost of 4
      Gy excluding the seminal vesicles. 22 patients (BAT group) were treated with
      daily stereotactic ultrasound positioning, for the other 20 patients (NoBAT
      group) an EPID (electronic portal imaging device) was performed once a week.
      Acute and late genito-urinary (GU) and rectal toxicity and PSA values were
      evaluated after 1.5, 3, 6, 9 and 12 months. The total median follow up of
      toxicity was 3 years in the BAT group and 4 years in the NoBAT group. RESULTS: In
      the NoBAT group significant more rectal toxicity occurred, while in GU toxicity
      no difference was seen. Two patients in the NoBAT group showed late rectal
      toxicity grade 3, no toxicity>grade 2 occurred in the BAT group. There was no
      significant difference in PSA reduction between the groups. CONCLUSION: Without
      BAT significant more acute and a trend to more late rectal toxicity was found.
      With regard to dose escalation this aspect is currently evaluated with a larger
      number of patients using intensity-modulated radiotherapy (IMRT).

PMID- 19107350
TI  - Image-guided radiotherapy for prostate cancer. Implementation of ultrasound-based
      prostate localization for the analysis of inter- and intrafraction organ motion.
AB  - PURPOSE: To evaluate inter- and intrafraction organ motion with an ultrasound
      based prostate localization system (BAT) for patients treated with intensity
      modulated radiotherapy for prostate cancer. PATIENTS AND METHODS: After set-up to
      external skin marks, 260/219 ultrasound-based alignments were performed
      before/after irradiation in 32 consecutive patients. Image quality was classified
      as good, satisfactory or poor. Patient- and imaging-related parameters were
      analyzed to identify predictors for poor image quality. Shifts in relation to the
      treatment planning computed tomography (CT) were recorded before/after
      irradiation in the superior-inferior (SI), anterior-posterior (AP) and right-left
      (RL) directions to determine inter-/intrafraction prostate motion. RESULTS: The
      thickness of tissue anterior to the bladder and bladder volume during the
      ultrasound localization as well as an inferior prostate position relative to
      public symphysis (determined in treatment planning CT) were found to be
      independent predictors of a poor image quality. Interfraction shifts (mean+/
      standard deviation: -0.2+/-4.8 [SI], 2.4+/-6.6 [AP] and 1.9+/-4.6 [RL]) varied
      much stronger than intrafraction shifts (0.0+/-2.0 [SI], 0.6+/-2.2 [AP] and 0.2+/
      1.9 [RL]). A larger pressure of the ultrasound probe (determined as a larger
      reduction of the distance abdominal skin to prostate between the planning CT and
      the ultrasound) was applied in case of poor image quality, associated with larger
      systematic posterior prostate displacements. CONCLUSION: Intrafraction prostate
      shifts are considerably smaller in comparison to interfraction shifts. Bladder
      filling and a small pressure on the ultrasound probe are crucial to achieve an
      adequate image quality without systematic prostate displacements.

PMID- 19107351
TI  - Sodium butyrate enemas in the treatment of acute radiation-induced proctitis in
      patients with prostate cancer and the impact on late proctitis. A prospective
      evaluation.
AB  - PURPOSE: To evaluate prospectively the effect of sodium butyrate enemas on the
      treatment of acute and the potential influence on late radiation-induced
      proctitis. PATIENTS AND METHODS: 31 patients had been treated with sodium
      butyrate enemas for radiation-induced acute grade II proctitis which had
      developed after 40 Gy in median. During irradiation the toxicity was evaluated
      weekly by the Common Toxicity Criteria (CTC) and subsequently yearly by the RTOG
      (Radiation Therapy Oncology Group) and LENT-SOMA scale. RESULTS: 23 of 31
      patients (74%) experienced a decrease of CTC grade within 8 days on median. A
      statistical significant difference between the incidence and the severity of
      proctitis before start of treatment with sodium butyrate enemas compared to 14
      days later and compared to the end of irradiation treatment course, respectively,
      was found. The median follow-up was 50 months. Twenty patients were recorded as
      suffering from no late proctitis symptom. Eleven patients suffered from grade I
      and 2 of these patients from grade II toxicity, too. No correlation was seen
      between the efficacy of butyrate enemas on acute proctitis and prevention or
      development of late toxicity, respectively. CONCLUSION: Sodium butyrate enemas
      are effective in the treatment of acute radiation-induced proctitis in patients
      with prostate cancer but have no impact on the incidence and severity of late
      proctitis.

PMID- 19107352
TI  - Preparation and identification of scFv and bsFv against transferrin receptor.
AB  - To obtain single chain variable fragment (scFv) and bivalent single chain
      variable fragment (bsFv) against transferrin receptor, up-stream and down-stream
      primers were designed according to the complementary sequences of FR1 region of
      variable heavy (VH) and FR4 of variable light (VL), respectively, which contained
      inter-linker G4S and the restriction endonuclease SfiI, AscI and NotI. Two pieces
      of scFv fragments were first amplified through PCR and then inserted into plasmid
      pAB1, which could express scFv protein once induced by IPTG in the host bacteria.
      To express scFv and bsFv, E. coli TG1 was cultured in LB broth and was induced by
      IPTG. The restriction enzyme digestion map and DNA sequencing demonstrated that
      scFv and bsFv genes were successfully inserted into the expression plasmid. SDS
      PAGE and Western blotting revealed the protein band at 35kD and 60kD, which were
      consistent with the molecular weight of scFv and bsFv respectively. Flow
      cytometry showed that scFv and bsFv harbored the specific binding activity with
      TfR expressed in various tumor cells, and the avidity of bsFv was higher than
      that of the parent scFv.

PMID- 19107353
TI  - Packaging and functional identification of recombinant adeno-associated virus
      encoding cdc2-siRNA.
AB  - Cyclin dependent kinases (cdks) play an important role in the pathogenesis of
      multiple neurodegenerative diseases. To explore the possibility of cdks-related
      gene therapy for neurodegenerative diseases, we packed recombinant adeno
      associated virus (rAAV) encoding cdc2-siRNA. The expressing plasmid pAAV-MCS-EGFP
      U6-cdc2-siRNA was constructed by using molecular biological techniques. The rAAV
      encoding cdc2-siRNA (rAAV-EGFP-U6-cdc2-siRNA) was packed by calcium phosphate
      mediated co-transfection of the plasmid pAAV-MCS-EGFP-U6-cdc2-siRNA, p-RC and p
      Helper into AAV-293 cells. DNA sequencing proved the successful construction of
      U6-cdc2-siRNA in pAAV-MCS-EGFP. Seventy-two h after packaging, the expression of
      EGFP could be detected in AAV-293 cells. Western blotting revealed that cdc2 gene
      expression in AAV-293 cells was down-regulated markedly after transfection with
      rAAV-EGFP-U6-cdc2-siRNA, which evidenced the satisfactory silencing effect of
      this virus. It was concluded that the packaging of rAAV encoding cdc2-siRNA was
      successful. rAAV encoding cdc2-siRNA could silence cdc2 gene effectively, which
      might offer a novel means for the treatment of neurodegenerative diseases.

PMID- 19107354
TI  - Spectrophotometric determination of trimethylamine-nitrogen in cadaver tissues
      for the estimation of late postmortem interval: a pilot study.
AB  - To study the relationship between the late postmortem interval (PMI) and
      trimethylamine-nitrogen (TMA-N) in postmortem tissues of cadaver, TMA-N in
      muscles, livers and kidneys of rats was measured at different postmortem
      intervals (PMI) by using a modified spectrophotometric method. The results
      indicated that the detection sensitivity of TMA-N was 1 mg/L, and there was a
      good linear correlation between the value of absorbance (A value) and TMA-N at
      the concentration of 1-10 mg/L (R (2) = 0.9991). Although TMA variation in
      muscles was different from that in inner organs during the time since death, TMA
      N changes in cadaver tissues was positively correlated with PMI. During 2 to 7 d
      since death, the best correlation between PMI and TMA-N concentration was found
      in muscles. With PMI as an independent variable, the cubic polynomial regression
      equation was y= -0.457x(3)+6.519x(2)-24.574x+27.207 (R (2)=0.969). During 3 to 8
      days since death, PMI was best correlated with TMA-N concentration in inner
      organs. With PMI as the independent variable, the cubic polynomial regression
      equation was y=0.509x(3)-9.153x(2)+55.727x-95.819 (R (2)=0.953). It was concluded
      that TMA-N in tissues could be used as a new estimator for late PMI. The method
      used in this study offered advantages such as accuracy, sensitivity, little
      samples required and wide PMI estimation.

PMID- 19107355
TI  - Effects of betulinic acid on proliferation and apoptosis in Jurkat cells and its
      in vitro mechanism.
AB  - The anti-cancer effects of betulinic acid (BA) on Jurkat cells and its in vitro
      mechanism were examined by using MTT assay. Apoptosis was detected by using
      Hoechst33258 staining and annexin-V/PI double-labeled cytometry. The effects of
      betulinic acid on the cell cycle of Jurkat cells were studied by propidium iodide
      method. RT-PCR and Western blotting were used to analyze the changes of cyclin
      D3, bcl-xl mRNA and protein levels in Jurkat cells after treatment with betulinic
      acid. Our results showed the proliferation of Jurkat cells was decreased in
      betulinic acid-treated group with a 24-h IC50 value being 70.00 mumol/L.
      Betulinic acid induced apoptosis of Jurkat cells in a time- and dose-dependent
      manner. The number of Jurkat cells treated with betulinic acid showed an increase
      in G(0)/G(1) phase and decrease in S phase. After treatment with 0, 20, 60, 100
      mumol/L betulinic acid for 24 h, the number of Jurkat cells was increased from
      (31.00+/-1.25)% to (58.84+/-0.32)% in G(0)/G(1) phase, whereas it was decreased
      from (61.45+/-1.04)% to (35.82+/-1.95)% in S phase. PBMCs were less sensitive to
      the cytotoxicity of betulinic acid than Jurkat cells. The expressions of cyclin
      D3, bcl-xl mRNA and protein were decreased sharply in Jurkat cells treated with
      betulinic acid. It is concluded that betulinic acid is able to inhibit the
      proliferation of Jurkat cells by regulating the cell cycle, arrest cells at
      G(0)/G(1) phase and induce the cell apoptosis. The anti-tumor effects of
      betulinic acid are related to the down-regulated expression of cyclin D3 and bcl
      xl.

PMID- 19107356
TI  - Implantation of lumenless pacing leads at the inter-atrial septum and right
      ventricular outflow tract with deflectable catheter-sheath.
AB  - Current permanent right ventricular and right atrial endocardial pacing leads are
      implanted utilizing a central lumen stylet. Right ventricular apex pacing
      initiates an abnormal asynchronous electrical activation pattern, which results
      in asynchronous ventricular contraction and relaxation. When pacing from right
      atrial appendage, the conduction time between two atria will be prolonged, which
      results in heterogeneity for both depolarization and repolarization. Six patients
      with Class I indication for permanent pacing were implanted with either single
      chamber or dual chamber pacemaker. The SelectSecure 3830 4-French (Fr) lumenless
      lead and the SelectSite C304 8.5-Fr steerable catheter-sheath (Medtronic Inc.,
      USA) were used. Pre-selected pacing sites included inter-atrial septum and right
      ventricular outflow tract, which were defined by ECG and fluoroscopic criteria.
      All the implanting procedures were successful without complication. Testing
      results (mean atrial pacing threshold: 0.87 V; mean P wave amplitude: 2.28 mV;
      mean ventricular pacing threshold: 0.53V; mean R wave amplitude: 8.75 mV) were
      satisfactory. It is concluded that implantation of a 4-Fr lumenless pacing lead
      by using a streerable catheter-sheath to achieve inter-atrial septum or right
      ventricular outflow tract pacing is safe and feasible.

PMID- 19107358
TI  - The effect of vitamin A on secretion of IFN-gamma and IL-4 in A549 cells induced
      by Mycoplasma pneumoniae.
AB  - In order to investigate the effect of vitamin A (VA) on the secretion of IFN
      gamma and IL-4 in Mycoplasma Pneumoniae (MP)-induced A549 cells, A549 cells were
      co-cultured with MP for different time lengths and then the levels of IFN-gamma
      and IL-4 in the cell culture supernatants were detected before and after
      treatment with different concentrations of VA by using the enzyme-linked
      immunosorbent assay (ELISA). The results showed that the level of IFN-gamma and
      IL-4 in the supernatants of MP-induced A549 cells was much higher than that in
      non-induced cells (P<0.01). After application of VA, IL-4 level was not increased
      until the concentration of VA was up to 0.5x10(-5) mol/L (P<0.01). However, with
      concentration of VA increased up to 1x10(-4) mol/L, IL-4 was significantly
      suppressed (P<0.01). It was concluded that MP could induce the secretion of IFN
      gamma and IL-4 in A549 cells. VA could inhibit the secretion of IFN-gamma and
      increase the IL-4 level in MP-induced A549 cells. However, high concentration of
      VA had an inhibitory effect on the secretion of IL-4 as well as on the IFN-gamma.
      These data provided a theoretical basis for the application of VA in MP pneumonia
      in the clinical practice.

PMID- 19107357
TI  - Changes of CD4(+) CD25 (+) regulatory T cells in peripheral blood in patients
      with hepatocellular carcinoma before and after TACE.
AB  - This study investigated the changes of CD4(+) CD25(+) regulatory T cells (Tregs)
      in peripheral blood of patients with hepatocellular carcinoma before and after
      transcatheter arterial chemoembolization (TACE). The proportion of CD4(+) CD25(+)
      Tregs among CD4(+) T lymphocytes in peripheral blood of 33 patients with
      hepatocellular carcinoma was determined by flow cytometry before, 1 week and 1
      month after TACE. And 25 healthy volunteers served as control. One month after
      TACE, the patients were divided into two groups: 22 in group A, who were in
      stable condition or getting better; and 10 in group B, who were deteriorating.
      One patient died and was excluded. The results showed that the percentage of
      CD4(+)CD25(+) Tregs among CD4(+) T lymphocytes did not significantly change in
      the 33 patients 1 week after TACE as compared with that before TACE, however, the
      difference was significant (P<0.01) between the patients with hepatocellular
      carcinoma and the healthy subjects. The percentage of CD4(+) CD25(+) Tregs among
      CD4(+) T lymphocytes in group A 1 month after TACE was decreased significantly in
      comparison with that before and 1 week after TACE (P<0.01), whereas, that in
      group B was increased significantly 1 month after TACE (P<0.01). It was concluded
      that patients with hepatocellular carcinoma had a higher proportion of
      CD4(+)CD25(+) Tregs in peripheral blood. TACE did not significantly affect the
      level of CD4(+) CD25(+) Tregs within short time (such as 1 week). The proportion
      of CD4(+)CD25(+) Tregs in peripheral blood 1 month after TACE was related to the
      prognosis of hepatocellular carcinoma.

PMID- 19107359
TI  - Polymorphism of apolipoprotein A5 is a risk factor for cerebral infarction in
      type 2 diabetes.
AB  - This study investigated the association of apolipoprotein A5 (apoA5) gene
      polymorphism at position -1131T>C with cerebral infarction in patients with type
      2 diabetes. A total of 256 type 2 diabetic patients without cerebral infarction
      (T2DM), 220 type 2 diabetic patients with cerebral infarction (T2DMCI) and 340
      healthy subjects were recruited from the same region (Hubei province, China). The
      genotype of apoA5 -1131T[Symbol: see text]C was analyzed by polymerase chain
      reaction, followed by restriction fragment length polymorphism (PCR-RFLP). Total
      cholesterol, HDL cholesterol, LDL-cholesterol and triglycerides were
      quantitatively detected by using standard enzymatic techniques. The results
      showed that the prevalence of the apoA5 -1131C allele was significantly higher in
      T2DMCI group than that in control group (42.7% versus 31.2%, P<0.01). The
      carriers of rare C allele had higher TG levels as compared with carriers of
      common allele in the three groups (P<0.01). Logistic regression models, which
      were adjusted for age, gender, blood pressure, BMI, FBS, smoking, LDL-C and HDL
      C, revealed that patients carrying the apoA5 -1131C allele and CC homozygotes
      were at high risk for T2DMCI. It was concluded that the apoA5 -1131C allele
      variant is an independent genetic risk factor for T2DMCI.

PMID- 19107360
TI  - Expression of platelet membrane glycoprotein Ib/IX/V complex, a receptor of
      thrombin, in patients with hemorrhagic thrombopathy.
AB  - To investigate the role of platelet membrane glycoprotein (GP) Ib/IX/V complex
      and its subunit GP Ibalpha in patients with hemorrhagic thrombopathy (HT), the
      expressions of GP Ib/IX/V complex and GP Ibalpha, defined as mean fluorescence
      intensity (MFI), were assessed by flow cytometry. The maximum aggregation of
      platelet was determined by turbidity method. These indicators were compared among
      68 HT patients with the presenting complaint of hemorrhage, 33 well-controlled HT
      patients and 32 normal healthy subjects. The results showed that the MFI of GP
      Ib/IX/V complex and GP Ibalpha was markedly lower in HT patients with current
      hemorrhage than that in the healthy subjects, with difference being statistically
      significant (P<0.05). There was no significant difference in the expressions of
      GP Ib/IX/V complex and GP Ibalpha between well-controlled HT patients and normal
      healthy subjects (P>0.05). It was concluded that the expression of GP Ib/IX/V
      complex, the receptor of thrombin and von Willebrand factor, was down-regulated
      in HT patients with current hemorrhage, which might result in the dysfunction of
      platelet aggregation and recurrence of HT.

PMID- 19107361
TI  - Effects of endotoxin on liver Smac apoptosis channel.
AB  - To study the effect of endotoxin on liver apoptosis, L02 liver cells were
      cultured and passaged in vitro, and then stimulated by endotoxin at 10 mg/mL for
      4, 8, 16 and 24 h respectively. Liver apoptosis was flow cytometrically and
      fluorescently detected. Immunohistochemistry was used to detect the delivery of
      smac and caspase9. The delivery of liver cell smac and the activity of caspase3
      were measured by caspase3 assay kit. The hepatic failure models of rats were
      established by using D-galactosamine. The blood serum and liver tissues were
      collected for the detection of the liver function, the level of endotoxin and the
      activity of caspase3 by using chromogenic substrate limulus amebocyte lysate
      method (LAL) and caspase3 active assay kit. The expression of smac and caspase9
      in liver cells was detected by Western blotting. With in vitro study, the L02
      cells stimulated by LPS condensed into conglobation and formed apoptotic bodies.
      After those cells were stained by hoechst, the apoptotic cells displayed blue
      color under the fluorescent microscope. The apoptosis rate was increased over
      time and the apoptosis was mainly of advanced stage. Meanwhile, the rate of smac
      delivery and activity of caspase9 and caspase3 were increased on L02 cell
      membrane. In vivo, hepatic failure and obvious endotoxemia were induced by
      injection of more than 200 mg/kg D-GalN. Hepatic mitochondria smac was reduced
      with dosage of D-GalN and, on the contrary, the activity of caspase3 was
      increased. D-GalN at 200 mg/kg increased Caspase9 while D-GalN at 300 mg/kg
      decreased caspase9. Mitochondria signal channel plays an important role in the
      endotoxin-induced apoptosis of hepatic cells by promoting the release of smac
      from mitochondria to cytoplasm and activating caspase9 and caspase3 in its low
      level channel.

PMID- 19107362
TI  - The effect of RhoC siRNA on the invasiveness and proliferation of human cervical
      cancer cell line SiHa cells.
AB  - This study investigated the effect of RhoC GTPase on the proliferation and
      metastasis of cervical cancer cells, SiHa cells, in vitro. RhoC siRNA was
      introduced into SiHa cells to silence the RhoC gene. The mRNA and protein
      expression of RhoC, before and after RhoC siRNA transfection, was examined by RT
      PCR and Western blotting, respectively. The proliferation and apoptosis of SiHa
      cells were examined by MTT assay and flow cytometry (FACS), respectively.
      Adhesive rate was evaluated by Matrigel adhesive assay, and the invasive
      capability and migration capability were assessed by transwell invasive assay and
      migration assay, respectively. The results showed that after the RhoC siRNA
      transfection, the mRNA and protein expression of RhoC was down-regulated in SiHa
      cells. The down-regulation of RhoC GTPase did not affect the cell proliferation
      and apoptosis (P>0.05), but it did suppress SiHa cells' adhesion to matrigel
      (P<0.01), the invasive capability (P<0.01) and the migration capability (P<0.01).
      It was concluded that RhoC obviously promotes the adhesion, invasion and
      migration of SiHa cells in vitro, but not proliferation and apoptosis, suggesting
      that RhoC plays an important role in the progression in cervical cancer.

PMID- 19107363
TI  - Changes in number and biological function of endothelial progenitor cells in
      hypertension disorder complicating pregnancy.
AB  - To examine the changes in number and function of endothelial progenitor cells
      (EPCs) from peripheral blood (PB) in hypertension disorder complicating pregnancy
      (HDCP), 20 women with HDCP and 20 normal pregnant women at the third trimester
      were studied. Mononuclear cells (MNCs) from PB were isolated by Ficoll density
      gradient centrifugation. EPCs were identified by positive expression of both CD34
      and CD133 under fluorescence microscope and positive expression of factor VIII as
      shown by immunocytochemistry. The number of EPCs was flow-cytometrically
      determined. Proliferation and migration of EPCs were measured by MTT assay and
      modified Boyden chamber assay, respectively. The adhesion activity of EPCs was
      detected by counting the number of the adherent cells. The results showed that,
      compared with normal pregnant women, the number of EPCs was significantly reduced
      in HDCP (4.29%+/-1.21% vs 15.32%+/-2.00%, P<0.01), the functional activity of
      EPCs in HDCP, such as proliferation (13.45%+/-1.68% vs 18.45%+/-1.67%), migration
      (37.25+/-7.28 cells/field vs 67.10+/-9.55 cells/field) and adhesion activity
      (20.65+/-5.19 cells/field vs 34.40+/-6.72 cells/filed) was impaired (P<0.01). It
      is concluded that the number and function of EPCs are significantly decreased in
      HDCP.

PMID- 19107364
TI  - Expression and clinical implication of HIF-1alpha and VEGF-C in non-small cell
      lung cancer.
AB  - To study the expression and implication of HIF-1alpha and VEGF-C in non-small
      cell lung cancer (NSCLC) and its relationship with clinical pathological features
      of NSCLC, immunohistochemical SP was used to detect the expression of HIF-1alpha
      and VEGF-C proteins in 48 NSCLC tissues and the same para-cancerous tissues. The
      positive rates of HIF-1alpha and VEGF-C were 70.8% (34/48) and 68.8% (33/48)
      respectively. The expression of HIF-1alpha protein was detected in a
      significantly greater proportion in NSCLC carcinoma tissues than that in para
      cancerous tissues (12.5% and 16.7%, P<0.05). The positive rates of HIF-1alpha and
      VEGF-C were correlated with lymph node metastasis and TNM stage. No relationship
      was found between the two factors and age, sex, pathological subtypes and
      histological grades. The positive rates between HIF-1alpha and VEGF-C were
      correlated (P<0.05). HIF-1alpha and VEGF-C were over-expressed in NSCLC. They may
      be involved in the carcinogenesis of NSCLC, and play an important role in
      invasion and metastasis of NSCLC. HIF-1alpha and VEGF-C work synergically in the
      process of NSCLC.

PMID- 19107366
TI  - Application of pulmonary venoplasty in the surgical treatment of lung cancer.
AB  - Presented in this study were three cases of lung cancer undergoing pulmonary
      venoplasty. In the 3 patients with central type of carcinoma of lung involving
      pulmonary vein, the main branch of right superior pulmonary vein and the distal
      end of the superior-lobe vein were occluded. The root part of the vein of right
      middle lobe, plus part of vessel of of right superior vein was resected. The
      right superior vein was reconstructed by continuous 6-0 Prolene sutures. After
      the operation, the reconstructed was patent and the surgical margin was tumor
      free. Postoperatively, clinical manifestations and plain chest films did not show
      any signs of venous blockade. The patients were discharged healed 3 weeks after
      the operation. The technical details of the surgery were presented, the
      improvements on the basis of traditional methods were discussed and its clinical
      application was evaluated. It is concluded that pulmonary venoplasty is a safe
      and feasible operation. Further improvement of the surgery will help conserve
      more lung tissue and benefit more patients because of expanded indications.

PMID- 19107365
TI  - Analysis of prognostic factors for surgery after neo-adjuvant therapy for stage
      III non-small cell lung cancer.
AB  - In order to explore the possibility to predict the risk factors for postoperative
      complications and survival time, the clinical data of 152 patients (including 116
      males and 36 females) who had undergone neo-adjuvant therapy and surgery for
      stage IIIA and B non-small cell lung cancer (NSCLC) were retrospectively
      analyzed. Demographic data, preoperative functional parameters, staging,
      induction regimen (chemotherapy alone or associated with radiotherapy),
      associated disorders, and data about operation were collected. Chi-square test
      and multivariate analysis fitting the unconditional logistic regression model
      were performed to identify predictors of postoperative complications, while
      Kaplan-Meier and multivariate Cox proportional hazard model were employed to
      identify predictors of survival time, respectively. The univariate analysis
      demonstrated that forced expiratory volume in 1 second predicted percent (FEV1%,
      P=0.040) and associated disorders (P=0.020) were the predictive factors of
      complications, but multivariate analysis found no independence factors (P>0.05)
      of it. Univariate Kaplan-Meier analysis showed that stage (P=0.050) and
      pneumonectomy (P=0.018) affected the survival time. However, multivariate Cox
      proportional hazard model analysis demonstrated that only pneumonectomy (P=0.026)
      was associated with a decreased survival time, but no differences between right
      and left pneumonectomy were found. The results suggest that the risk factor for
      postoperative complications is acceptable, and pneumonectomy is associated with
      increased mortality, which should be performed only in stage III NSCLC patients.

PMID- 19107367
TI  - In vitro chemosensitivity testing of primary and recurrent breast carcinomas and
      its clinical significance.
AB  - In this study, in vitro chemosensitivity testing was conducted on primary
      cultured breast cancer cells from 96 patients with breast cancer, and the results
      showed that the cells from a few patients with primary breast cancer developed
      multidrug resistance (MDR) prior to the first chemotherapy exposure. All the
      cells from the recurrent cancer patients had MDR. The findings suggested that
      patients having MDR would benefit from high-dose chemotherapy (HDC) regimens. In
      vitro chemosensitivity screening, which was aimed at improving the therapeutic
      efficacy and minimizing side effects, helps in choosing individualized treatment
      for breast cancer.

PMID- 19107368
TI  - Surgical treatment of giant recurrent breast phyllodes tumor.
AB  - In this study, a recurrent massive phyllodes tumor of the breast was surgically
      removed and the grafting was used to repair the local skin defects. A 29-y female
      patient had recurring breast phyllodes tumor of extremely large size in the chest
      wall after the excision of a previous tumor. The massive phyllodes tumor was
      eliminated by completely removing the layers of the skin and tissues above the
      costal bones with incisal margin being 2 cm away from the tumor lesion. The
      latissimus dorsi myocutaneous flap, lateral thoracic skin flap, and rectus
      abdominis myocutaneous flap were grafted to replace the lost tissues due to the
      surgery. Anti-infection and anticoagulation treatments were used after the
      surgery. The graft flaps had sufficient blood supply and good blood circulation,
      and the incisions mostly healed. The outcome of the surgery was acceptable. For
      the surgical treatment of the massive phyllodes tumor in the chest wall, it is an
      alternative of choice to use latissimus dorsi myocutaneous flap, lateral thoracic
      skin flap and rectus abdominis myocutaneous flap in combination for skin
      grafting.

PMID- 19107369
TI  - Relationship between single nucleotide polymorphisms in -174G/C and -634C/G
      promoter region of interleukin-6 and prostate cancer.
AB  - The association between the single nucleotide polymorphisms (SNPs) in -174G/C and
      -634C/G of interleukin-6 (IL-6) promoter region and prostate cancer was examined
      in the population of Han people in Hubei region. TaqMan PCR was employed for the
      gene-typing of -174G/C and -634C/G in promoter region of IL-6 gene to compare the
      prostate cancer patients and normal controls in terms of genotype frequency,
      allele frequency and risk of prostate cancer. Enzyme-linked immunosorbent assay
      (ELISA) was used for the detection of IL-6 concentration in peripheral blood of
      the patients with prostate cancer and the relationship between the IL-6 level and
      the genotype was studied. Our results showed that in all the subjects, the
      genotype of genetic locus -174G/C was found to be GG and no CG and CC were
      observed. There was a significant difference in gene frequency of GG, CG and CC
      of -634C/G and allele frequency of G and C between prostate cancer patients and
      normal controls (P<0.05) and the gene frequency of GG+CG increased with the
      clinical stages and pathological grades of prostate cancer. The IL-6 level in
      GG+CG group was significantly higher than that in CC group. It was concluded that
      no SNP in -174G/C IL-6 promoter region was found in the population of Han people
      in Hubei region. The SNP in -634C/G was, to some extent, associated with the
      development and progression of prostate cancer. The population with GG+CG
      genetype has higher risk for prostate cancer.

PMID- 19107370
TI  - Inhibitory effect of matrine on the expression of PSA and AR in prostate cancer
      cell line LNCaP.
AB  - In order to investigate the inhibitory effect of matrine on the expression of
      prostate specific antigen (PSA) and androgen receptor (AR) in prostate cancer
      cell line LNCaP in vitro, LNCaP cells were treated with matrine at different
      concentrations (0.5, 1.0, 1.5, 2.0 g/L) for 12-36 h. The growth activities of
      cancer cells were determined by MTT colorimetric assay. The AR level was measured
      by Western blotting. The expression of PSA was detected by using AXSYM system
      chemical luciferase methods. The results showed that matrine could effectively
      inhibit the growth of androgen-dependent prostate cancer cell line LNCaP in vitro
      in a time- and dose-dependent manner (P<0.05). It could obviously decrease the
      level of AR (P<0.01) and inhibit the expression of PSA in a dose-dependent manner
      (P<0.05) in LNCaP cells. It was concluded that matrine could significantly
      suppress the growth of LNCaP cells and inhibit the expression of PSA and AR of
      prostate cancer cells.

PMID- 19107371
TI  - Correlations between event-related potentials with pictures recognition and WMS
      RC scores in patients with memory disorder caused by severe traumatic brain
      injury.
AB  - This study explored the possibility of using event-related potentials (ERP) for
      the measurement of picture-recognition memory and examined its correlation with
      the Chinese Wechsler Memory Scale-revised (WMS-RC) in patients with memory
      disorder caused by severe traumatic brain injury (sTBI). The subjects included 20
      sTBI patients with memory disorder and 22 healthy individuals. Memory function
      was measured by using WMS-RC. Behavioral and ERP responses were recorded on-line
      during performance on a battery of picture recognition and the responses were
      analyzed off-line for recognition memory effects. Mean memory quotient (MQ) of
      patients with sTBI was significantly lower than that of the control group. Mean
      reaction time (RT) was significantly longer and the mean correctness rate (CR) of
      picture recognition was significantly lower in sTBI group than that of the
      controls. In controls, the main components of average ERP of picture recognition
      includes two positive-going waves, designated as P(170) and P(500), that appear
      170 ms and 500 ms after stimulation when the subject could later successfully
      recall and recognize the pictures. P(500) amplitude of target stimulus was
      significantly higher than that of non-target stimulus. Compared to controls,
      P(500) responses of sTBI group were significantly delayed in latency (P<0.001)
      and lower in amplitude (P<0.001). P(500) latency showed significant negative
      correlation with MQ and the scores of "addition", "visual recognition", "picture
      recall", "visual reproduction" and "tactile memory" in WMS-RC. ERP of picture
      recognition provides a neurophysiological approach to directly assess memory
      impairment, and P(500) may serve as a helpful index for memory disorder caused by
      sTBI in forensic practice.

PMID- 19107372
TI  - The effect of hypercapnic acidosis preconditioning on rabbit myocardium.
AB  - This study observed the protective effect of hypercapnic acidosis preconditioning
      on rabbit heart suffered from ischemia-reperfusion injury. Hypercapnic acidosis
      was established in animals with mechanical hypoventilation before ischemia
      reperfusion. Thirty-two rabbits were randomly divided into 4 groups, with each
      having 8 animals in term of the degree of acidification: hypercapnic acidosis
      group A (group A), hypercapnic acidosis group B (group B), hypercapnic acidosis
      group C (group C), ischemia and reperfusion group (group IR). Animals in group IR
      were ventilated normally (tidal volume: 15 mL/kg, breathing rate 35 bpm). The
      PETCO(2) was maintained at the level of 40-50 mmHg for 30 min. Animals in groups
      A, B, C received low-frequency, low-volume ventilation to achieve hypercarbonic
      acidosis and the target levels of PETCO(2) were 75-85,65-75, 55-65 mmHg,
      respectively, with levels being maintained for 5 min. The animals then were
      ventilated normally to lower PETCO(2) to 40-50 mmHg. The left anterior branch
      artery of all the animals was ligated for 30 min and reperfused for 180 min. Then
      the infarct size was calculated. The cardiomyocytes were morphologically observed
      and ECG and hemodynamics were monitored on continuous basis. Acid-base balance
      was measured during procedure. Our results showed that the infarct size was
      (48.5+/-11.5)% of the risk area in the control group and (42.4+/-7.9)% in group C
      (P>0.05). Mean infarct size was significantly smaller in group B (34.5%+/-9.4%)
      (P<0.05 vs control group) and group A (31.0%+/-9.1%) (P<0.01 vs control group).
      It is concluded that HA-preconditioning can effectively protect the myocardium.

PMID- 19107373
TI  - Effects of propofol on the mRNA expression of toll-like receptor 4 in BV-2 cells
      during mimic ischemia-reperfusion injury in vitro.
AB  - This study investigated the effects of propofol on the mRNA expression of Toll
      like receptor-4 (TLR4) in BV-2 cells during mimic ischemia-reperfusion (I/R)
      injury in vitro. BV-2 cells, a mouse microglia line, were cultured and divided
      into 4 groups at random: control group (group C), ischemia/reperfusion group
      (group I/R), low-dose propofol (25 micromol/L) intervention group (group PF(25))
      and high-dose propofol (100 micromol/L) intervention group (group PF(100)). The
      mRNA expression of TLR4 and NF-kappaB was measured by means of RT-PCR. TNF-alpha
      levels in the supernatants of BV-2 cells were detected by ELISA. The results
      showed that the mRNA expression of TLR4 and NF-kappaB was significantly higher in
      groups I/R, PF(25) and PF(100) than in group C (P<0.01). And the TNF-alpha level
      in the supernatants was elevated in groups I/R, PF(25) and PF(100) as compared
      with that in group C (P<0.01). After pre-treatment with propofol, the mRNA
      expressions of TLR4 and NF-kappa B and the TNF-alpha level were significantly
      decreased in groups PF(25) and PF(100) in comparison to those in group I/R
      (P<0.01). And the decrease in those indicators was more significant in group
      PF(100) than in group PF(25) (P<0.01). It was concluded that propofol exerted
      brain-protecting effects during I/R injury by suppressing the mRNA expressions of
      TLR4 and NF-kappaB and deceasing the TNF-alpha level.

PMID- 19107374
TI  - Plastic changes of synapses and excitatory neurotransmitter receptors in facial
      nucleus following facial-facial anastomosis.
AB  - The remodeling process of synapses and neurotransmitter receptors of facial
      nucleus were observed. Models were set up by facial-facial anastomosis in rat. At
      post-surgery day (PSD) 0, 7, 21 and 60, synaptophysin (p38), NMDA receptor
      subunit 2A and AMPA receptor subunit 2 (GluR2) were observed by
      immunohistochemical method and semi-quantitative RT-PCR, respectively. Meanwhile,
      the synaptic structure of the facial motorneurons was observed under a
      transmission electron microscope (TEM). The intensity of p38 immunoreactivity was
      decreased, reaching the lowest value at PSD day 7, and then increased slightly at
      PSD 21. Ultrastructurally, the number of synapses in nucleus of the operational
      side decreased, which was consistent with the change in P38 immunoreactivity.
      NMDAR2A mRNA was down-regulated significantly in facial nucleus after the
      operation (P<0.05), whereas AMPAR2 mRNA levels remained unchanged (P>0.05). The
      synapses innervation and the expression of NMDAR2A and AMPAR2 mRNA in facial
      nucleus might be modified to suit for the new motor tasks following facial-facial
      anastomosis, and influenced facial nerve regeneration and recovery.

PMID- 19107375
TI  - Ultrasound speckle tracking imaging contributes to early diagnosis of impaired
      left ventricular systolic function in patients with type 2 diabetes mellitus.
AB  - To investigate the value of ultrasound speckle tracking imaging (STI) in the
      assessment of the short-axis and long-axis systolic function of the left
      ventricle (LV) in patients with type 2 diabetes mellitus (DM), 100 subjects with
      normal ejection fraction were studied, including 41 patients with DM only (DM
      group), 22 patients with both DM and left ventricular hypertrophy (DH group), and
      37 healthy subjects (control group). Left ventricle systolic function in the long
      axis defined as longitudinal strain, and that in the short axis defined as radial
      strain, apical and basal LV rotations, and LV twist were assessed respectively.
      The results showed that average peak strain in the long axis at basal, middle and
      apical levels, and global peak strain were significantly decreased in the patient
      groups when compared with the control group (P<0.001 for each). The parameters in
      DH group were significantly lower than those in DM group (P<0.01 for each). There
      were no significant differences in average radial peak strain in the short axis
      at different levels, and global peak strain among the three groups (P>0.05).
      Apical and basal LV rotations, and LV twist were greater in the patient groups
      than in the control group (P<0.01 for each). Basal LV rotation and LV twist were
      greater in DH group than those in DM group (P<0.01). It was concluded that STI
      may be used to identify early abnormalities in patients with type 2 DM that have
      normal left ventricular systolic function.

PMID- 19107376
TI  - Evaluation of carotid atherosclerotic plaque stability with contrast-enhanced
      ultrasonography.
AB  - This study was aimed to evaluate the relationship between carotid atherosclerotic
      plaque stability and the clinical symptoms in patients with carotid
      atherosclerotic plaques by using contrast-enhanced ultrasonography. Fifty
      patients with carotid atherosclerotic plaques were enrolled and examined with
      contrast-enhanced ultrasonography. The correlation of contrast agent enhancement
      of the carotid atherosclerotic plaques and the clinical symptoms was analyzed.
      The results showed that among the 50 patients, plaques were enhanced in the 23
      patients with obvious clinical symptoms. In 27 patients without apparent clinical
      symptoms, plaques were enhanced sparsely in 15 patients and not enhanced in 12
      patients. It was suggested that contrast-enhanced ultrasonography could be used
      for the examination of the microcirculation in carotid atherosclerotic plaques on
      real-time basis and serve as a new noninvasive approach for the assessment of
      stability of carotid atherosclerotic plaques.

PMID- 19107377
TI  - Value of quantitative tissue velocity imaging in the detection of regional
      myocardial function in dogs with acute subendocardial ischemia.
AB  - This study evaluated the application of quantitative tissue velocity imaging
      (QTVI) in assessing regional myocardial systolic and diastolic functions in dogs
      with acute subendocardial ischemia. Animal models of subendocardial ischemia were
      established by injecting microspheres (about 300 microm in diameter) into the
      proximal end of left circumflex coronary artery in 11 hybrid dogs through
      cannulation. Before and after embolization, two-dimensional echocardiography,
      QTVI and real-time myocardial contrast echocardiography (RT-MCE) via intravenous
      infusion of self-made microbubbles, were performed, respectively. The systolic
      segmental wall thickening and subendocardial myocardial longitudinal velocities
      of risk segments before and after embolization were compared by using paired t
      analysis. The regional myocardial video intensity versus contrast time could be
      fitted to an exponential function: y=A.(1-exp(-beta.t)), in which the product of
      A and beta provides a measure of myocardial blood flow. RT-MCE showed that
      subendocardial normalized A.beta was decreased markedly from 0.99+/-0.19 to
      0.35+/-0.11 (P<0.05) in 28 left ventricular (LV) myocardial segments after
      embolization, including 6 basal and 9 middle segments of lateral wall (LW), 8
      middle segments of posterior wall (PW) and 5 middle segments of inferior wall
      (IW). However, there was no statistically significant difference in subepicardial
      layer before and after embolization. Accordingly, the ratio of A.beta of
      subendocardial myocardium to subepicardial myocardium in these segments was
      significantly decreased from 1.10+/-0.10 to 0.31+/-0.07 (P<0.05). Although the
      systolic wall thickening did not change 5 min after the embolization in these
      ischemic segments (29%+/-3% vs 31%+/-5%, P>0.05), the longitudinal peak systolic
      velocities (Vs) and early-diastolic peak velocities (Ve) recorded by QTVI were
      declined significantly (P<0.05). Moreover, the subendocardial velocity curves
      during isovolumic relaxation predominantly showed positive waves, whereas they
      mainly showed negative waves before the embolization. This study demonstrates
      that QTVI can more sensitively and accurately detect abnormal regional myocardial
      function and post-systolic systole caused by acute subendocardial ischemia.

PMID- 19107378
TI  - The value of conventional echocardiographic and tissue doppler imaging in the
      diagnosis of cardiac amyloidosis.
AB  - Transthoracic echocardiographic characteristics of 17 cases of cardiac
      amyloidosis (CA), a rare disease in China, were analyzed in order to improve the
      understanding of the disease. Seventeen cases of biopsy-proven CA, admitted to
      Wuhan Union Hospital from June 1994 to September 2008 were retrospectively
      reviewed. Twenty normal volunteers served as control group. Left atrial and
      ventricular functions and mitral inflow velocity were measured by two
      dimensional, and Doppler echocardiography, and tissue Doppler imaging (TDI)
      derived peak systolic wall motion velocities (Sv), peak early diastolic wall
      motion velocities (Ev), and peak late diastolic wall motion (Av) were measured at
      the septum, lateral, inferior and anterior corners of mitral annulus from the
      apical 4- and 2 chamber views. Compared with the control group, the
      interventricular septal thickness (IVSd), the left ventricular posterior wall
      (LVPWd), right ventricular transverse diameter (RVTDd) near the end of diastole
      and the interauricular septum thickness (IASs), left atrial anteroposterior
      diameter (LAADs), right atrial transverse diameter (RATDs) near the end of
      systole were increased significantly (all P<0.05) and left ventricular ejection
      fraction (LVEF) decreased (P<0.05) in the CA group. Compared with the control
      group, Sv, Ev at each wall and Av at almost all walls were significantly
      decreased in the CA group. In the CA group, Myocardial echoes of interventricular
      septum and free wall of left ventricle were enhanced evidently and distributed
      unevenly. The echoes presented as ground glass-like images, with some spotty
      hyper echoes. Both atria were enlarged, and LVEF decreased, with diastolic
      function impaired, and mild-moderate hydropericardium found in the CA group. It
      was concluded that echocardiography was a relatively sensitive and highly
      specific non-invasive method for the diagnosis of CA.

PMID- 19107379
TI  - Diffusion-weighted single-shot echo planar MR imaging of normal human prostate
      using different b values.
AB  - This study examined the effect of different b values on diffusion-weighted MR
      imaging (DWI) of human prostate by using single-shot spin echo echo planar
      imaging (SE-EPI) sequences, observed the normal appearances and measured apparent
      diffusion coefficient (ADC) values in anatomical regions of normal prostate.
      Twenty-four healthy volunteers (mean age: 32 y) were studied by using a 1.5T
      system with a phased array surface multicoil. Two kinds of single-shot SE-EPI
      sequence were used to perform DWI in the prostate in volunteers, with five b
      values being 0, 30, 300, 500 to 1000 s/mm(2). The image quality with different
      imaging parameters was analyzed and the ADC values in anatomical regions of
      normal prostate were measured. DWI of prostate was successfully obtained in all
      volunteers. The images were of good quality, without artifacts containing pixels
      within the prostate. The contrast was good between the different anatomical
      regions of the prostatic gland, i.e., the peripheral zone (PZ), which exhibited
      higher signal intensity, and the central gland (CG). Signal intensity contrast
      was related to the magnitude of b values. The ADC values in PZ and CG were
      (1.27+/-0.22)x10(-3) mm(2)/s and (1.01+/-0.17)x10(-3) mm(2)/s, respectively. The
      ADC values were found to be significantly higher in PZ than in CG (P<0.05, paired
      t-test). Significant differences were found between the slice-selecting component
      and both the read-out and phase-encoding components of the ADC values. It is
      concluded that SE-EPI is a suitable DWI sequence for human prostate. The contrast
      between PZ and CG is good when b values are low, while the diffusion and ADC
      values are accurate when b values are high. ADC values are higher in PZ than in
      CG in normal prostate. Diffusional anisotropy is present in normal prostatic
      tissue.

PMID- 19107380
TI  - An informative set of SSLP markers and genomic profiles in the rat MHC, the RT1
      complex.
AB  - Almost 10,000 single nucleotide polymorphisms (SNPs) had been identified in the
      RT1 complex, the major histocompatibility complex of the rat, but less than
      approximately 0.5% have been characterized. In the context of the incomplete
      characterization of most SNPs, simple sequence length polymorphism (SSLP) marker
      development is still valuable for understanding the involvement of genes in the
      RT1 in controlling disease susceptibility, since SSLPs are user-friendly and cost
      effective genetic markers in rat genome analysis. In this study, we developed a
      set of 67 SSLP markers, including 57 novel markers, to cover the entire RT1
      complex and then created genetic profiles across 67 rat strains. These markers
      are located almost every 50 kb in the RT1 complex and show comparable
      polymorphism; the average number of alleles was 8.04 +/- 3.44 and the average
      polymorphic rate was 71 +/- 23%. Interestingly, markers failing to amplify
      polymerase chain reaction products were highly observed in all strains except for
      BN/SsNHsd, which suggests the existence of highly variable genomic sequences or
      genomic rearrangements in the RT1 region across rat strains. Based on the
      phylogenic tree and individual genotyping data, we identified 28 SSLP marker
      haplotypes in the RT1 region that roughly consisted of three genomic regions.
      These findings provided new insight into the genomic organization of the RT1
      complex and we recognized the need of additional RT1 genome sequences in
      different strains. Owing to the accuracy and ease of determination, PCR-based
      SSLP genotyping could replace serological typing in genetic analyses and
      characterization of rat major histocompatibility.

PMID- 19107382
TI  - The association between socioeconomic status and osteoporotic fracture in
      population-based adults: a systematic review.
AB  - Although socioeconomic status (SES) is inversely related to most diseases, this
      systematic review showed a paucity of good quality data examining influences of
      SES on osteoporotic fracture to confirm this relationship. Further research is
      required to elucidate the issue and any underlying mechanisms as a necessary
      precursor to considering intervention implications. INTRODUCTION: The association
      between socioeconomic status (SES) and musculoskeletal disease is little
      understood, despite there being an inverse relationship between SES and most
      causes of morbidity. We evaluated evidence of SES as a risk factor for
      osteoporotic fracture in population-based adults. METHODS: Computer-aided search
      of Medline, EMBASE, CINAHL, and PsychINFO from January 1966 until November 2007
      was conducted. Identified studies investigated the relationship between SES
      parameters of income, education, occupation, type of residence and marital
      status, and occurrence of osteoporotic fracture. A best-evidence synthesis was
      used to summarize the results. RESULTS: Eleven studies were identified for
      inclusion, which suggested a lack of literature in the field. Best evidence
      analysis identified strong evidence for an association between being
      married/living with someone and reduced risk of osteoporotic fracture. Limited
      evidence exists of the relationship between occupation type or employment status
      and fracture, or for type of residence and fracture. Conflicting evidence exists
      for the relationship between osteoporotic fracture and level of income and
      education. CONCLUSION: Limited good quality evidence exists of the role SES might
      play in osteoporotic fracture. Further research is required to identify whether a
      relationship exists, and to elucidate underlying mechanisms, as a necessary
      precursor to considering intervention implications.

PMID- 19107381
TI  - Characterization of 47 MHC class I sequences in Filipino cynomolgus macaques.
AB  - Cynomolgus macaques (Macaca fascicularis) provide increasingly common models for
      infectious disease research. Several geographically distinct populations of these
      macaques from Southeast Asia and the Indian Ocean island of Mauritius are
      available for pathogenesis studies. Though host genetics may profoundly impact
      results of such studies, similarities and differences between populations are
      often overlooked. In this study we identified 47 full-length MHC class I
      nucleotide sequences in 16 cynomolgus macaques of Filipino origin. The majority
      of MHC class I sequences characterized (39 of 47) were unique to this regional
      population. However, we discovered eight sequences with perfect identity and six
      sequences with close similarity to previously defined MHC class I sequences from
      other macaque populations. We identified two ancestral MHC haplotypes that appear
      to be shared between Filipino and Mauritian cynomolgus macaques, notably a Mafa-B
      haplotype that has previously been shown to protect Mauritian cynomolgus macaques
      against challenge with a simian/human immunodeficiency virus, SHIV(89.6P). We
      also identified a Filipino cynomolgus macaque MHC class I sequence for which the
      predicted protein sequence differs from Mamu-B*17 by a single amino acid. This is
      important because Mamu-B*17 is strongly associated with protection against simian
      immunodeficiency virus (SIV) challenge in Indian rhesus macaques. These findings
      have implications for the evolutionary history of Filipino cynomolgus macaques as
      well as for the use of this model in SIV/SHIV research protocols.

PMID- 19107383
TI  - The geographic availability and associated utilization of dual-energy X-ray
      absorptiometry (DXA) testing among older persons in the United States.
AB  - Using national Medicare data from 1999-2006, we evaluated the relationship
      between travel distance and receipt of dual-energy X-ray absorptiometry (DXA).
      After adjusting for potentially confounding factors, travel distance was strongly
      associated with DXA testing. Rural residents were most strongly dependent on the
      availability of DXAs performed in physician offices. INTRODUCTION: Medicare
      reimbursement for DXAs performed in non-facility settings (e.g., physician
      offices) decreased in 2007. With declining reimbursement, some DXA providers may
      cease providing this service, which would increase travel distance for some
      people. The impact of travel distance on access to DXA is unclear. METHODS: Using
      national Medicare data, we identified claims for DXA to evaluate trends in the
      number and locations of DXAs performed. Travel distance was the distance from
      beneficiaries' residence and the nearest DXA provider. Binomial regression
      evaluated the relationship between travel distance and receipt of DXA. RESULTS:
      In 2006, 2.9 million DXAs were performed, a 103% increase since 1999. In 2005
      2006, 8.0% of persons were tested at non-facility sites versus 4.2% at facility
      sites. The remainder (88%) had no DXA. Persons traveling 5-9, 10-24, 25-39, and
      40-54, and > or = 55 miles were less likely to receive DXA (adjusted risk ratios
      = 0.92, 0.79, 0.43, 0.32, and 0.26, respectively, < 5 miles referent). Rural
      residents were more dependent than urban residents on the availability of DXA
      from non-facility providers. CONCLUSION: Approximately two-thirds of DXAs in 2005
      2006 were performed in non-facility settings (e.g., physician offices). Rural
      residents would have preferentially reduced access to DXA if there were fewer non
      facility sites.

PMID- 19107384
TI  - Comparison of QCT-derived and DXA-derived areal bone mineral density and T
      scores.
AB  - Two-dimensional areal bone mineral density (aBMD) of the proximal femur measured
      by three-dimensional quantitative computed tomography (QCT) in 91 elderly women
      was compared to dual-energy X-ray absorptiometry (DXA) aBMD results measured in
      the same patients. The measurements were highly correlated, though QCT aBMD
      values were marginally lower in absolute units. Transformation of the QCT aBMD
      values to T score values using National Health and Nutrition Examination Survey
      (NHANES) DXA-derived reference data improved agreement and clinical utility.
      INTRODUCTION: World Health Organization guidelines promulgate aBMD (g cm(-2))
      measurement of the proximal femur for the diagnosis of bone fragility. In recent
      years, there has been increasing interest in QCT to facilitate understanding of
      three-dimensional bone structure and strength. OBJECTIVE: To assist in comparison
      of QCT-derived data with DXA aBMD results, a technique for deriving aBMD from QCT
      measurements has been developed. METHODS: To test the validity of the QCT method,
      91 elderly females were scanned on both DXA and CT scanners. QCT-derived DXA
      equivalent aBMD (QCT(DXA) aBMD) was calculated using CTXA Hip software (Mindways
      Software Inc., Austin, TX, USA) and compared to DXA-derived aBMD results.
      RESULTS: Test retest analysis indicated lower root mean square (RMS) errors for
      CTXA; F test between CTXA and DXA was significantly different at femoral neck
      (FN) and trochanter (TR) (p < 0.05). QCT underestimates DXA values by 0.02 +/-
      0.05 g cm(-2) (total hip, TH), 0.01 +/- 0.04 g cm(-2) (FN), 0.03 +/- 0.07 g cm(
      2) (inter-trochanter, IT), and 0.02 +/- 0.05 g cm(-2) (TR). The RMS errors
      (standard error of estimate) between QCT and DXA T scores for TH, FN, IT, and TR
      were 0.36, 0.40, 0.39, and 0.49, respectively. CONCLUSIONS: This study shows that
      results from QCT aBMD appropriately adjusted can be evaluated against NHANES
      reference data to diagnose osteoporosis.

PMID- 19107385
TI  - Comparison of direct health care costs related to the pharmacological treatment
      of osteoporosis and to the management of osteoporotic fractures among compliant
      and noncompliant users of alendronate and risedronate: a population-based study.
AB  - This population-based study aimed to compare direct health care costs related to
      the pharmacological treatment of osteoporosis and to the management of
      osteoporotic fractures among compliant and noncompliant users of alendronate and
      risedronate. During a 2-year follow-up period, compared to those with medication
      possession ratio (MPR) > or = 80%, women with MPR < 80% incurred significantly
      higher physician care costs and hospital care costs. INTRODUCTION: This study
      aimed to compare direct health care costs related to the treatment of
      osteoporosis and osteoporotic fractures among compliant and noncompliant users of
      alendronate and risedronate. METHODS: A cohort of 15,027 women having initiated
      alendronate or risedronate was identified. MPR and direct health care costs
      (physician care, hospital care, drugs) were assessed during a 2-year period.
      Regression models were used to estimate mean predicted cost for compliant (MPR >
      or = 80%) and noncompliant (MPR < 80%) women. RESULTS: Mean predicted physician
      care cost (in Canadian dollars) was $51 among women with MPR < 80% and $34 among
      those with MPR > or = 80%: mean difference $17, 95% confidence interval (CI) $2
      22. Mean predicted hospital care cost was $568 among women with MPR < 80% and
      $379 among those with MPR > or = 80%: mean difference $189, 95% CI $56-320. Mean
      predicted drug cost was $439 among women with MPR < 80% and $1,068 among those
      with MPR > or = 80%: mean difference $-639, 95% CI $-649 to -629. CONCLUSION:
      Compared to compliant women, noncompliant women incurred significantly higher
      physician care and hospital care costs. Due to lower drug costs, total direct
      health care costs were lower among noncompliant women.

PMID- 19107386
TI  - Can architecture be barbaric?
AB  - The title of this article is adapted from Theodor W. Adorno's famous dictum: 'To
      write poetry after Auschwitz is barbaric.' After the catastrophic earthquake in
      Kocaeli, Turkey on the 17th of August 1999, in which more than 40,000 people died
      or were lost, Necdet Teymur, who was then the dean of the Faculty of Architecture
      of the Middle East Technical University, referred to Adorno in one of his
      'earthquake poems' and asked: 'Is architecture possible after 17th of August?'
      The main objective of this article is to interpret Teymur's question in respect
      of its connection to Adorno's philosophy with a view to make a contribution to
      the politics and ethics of architecture in Turkey. Teymur's question helps in
      providing a new interpretation of a critical approach to architecture and
      architectural technology through Adorno's philosophy. The paper also presents a
      discussion of Adorno's dictum, which serves for a better understanding of its
      universality/particularity.

PMID- 19107387
TI  - Molecular identification of fecal pollution sources in water supplies by host
      specific fecal DNA markers and Terminal Restriction Fragment Length Polymorphism
      profiles of 16S rRNA gene.
AB  - Specific fecal DNA markers were investigated for major pollution sources, cow,
      human, and pig, and occurrence of the identified markers was analyzed in river
      waters using Terminal Restriction Fragment Length Polymorphism (T-RFLP)
      techniques and sequencing of 16S rDNA of Bacteroides-Prevotella. The unique and
      specific DNA markers for cow and human were identified as a 222 bp and 60 bp peak
      in HaeIII T-RFLP profiles, respectively, and the pig-specific marker was not
      identified but the unique T-RFLP profile of pig could be used as a substitution.
      Human-specific marker was detected in most of the river waters tested (92.1%) and
      T-RFLP profiles of river waters were shown to be similar to those of human feces.
      Cluster analysis of T-RFLP data showed that the fecal sources were multiple
      (human plus cow and human plus dairy cow) in most of the river waters. The
      phylogenetic analysis for the clones recovered from the fecal and water samples
      showed that the clones from cow formed a discreet cluster from those of other
      sources. The other clones from human, pig, and river water formed two groups all
      together. The results of this study could be used to identify and control the
      fecal pollution source in the bodies of water in Korea.

PMID- 19107388
TI  - Targeting the rpoB gene using nested PCR-restriction fragment length polymorphism
      for identification of nontuberculous mycobacteria in hospital tap water.
AB  - Nontuberculous mycobacteria (NTM) are ubiquitous in the environment and can cause
      nosocomial infections in immunocompromised patients. Recently the presence of NTM
      in public drinking water and hospital water distribution systems has been
      reported. Their ability to form biofilms and their resistance to chlorine both
      contribute to their survival and colonization in water distribution systems. Here
      we analyzed thirty-two hospital tap water samples that were collected from
      different locations in three hospitals so as to evaluate the prevalence of NTM
      species. The water samples were concentrated by membrane filtration and then
      eluted with sterilized water following sonication. Two-step direct PCR targeting
      the rpoB gene, restriction fragment length polymorphism (RFLP) using the MspI
      restriction enzyme, and sequence analysis were performed for identification of
      NTM to the species level. The sequences of each PCR product were analyzed using
      BLASTN. Seven samples (7/32, 21.9%) were positive for NTM as determined by nested
      PCR. The PCR-RFLP results indicated five different patterns among the seven
      positive PCR samples. The water-born NTM were identified, including M.
      peregrinum, M. chelonae (2 cases), M. abscessus, M. gordonae (2 cases), and
      Mycobacterium sp. JLS. The direct two-step PCR-RFLP method targeting the rpoB
      gene was effective for the detection and the differentiation of NTM species from
      hospital tap water.

PMID- 19107389
TI  - Monitoring nutrient impact on bacterial community composition during
      bioremediation of anoxic PAH-contaminated sediment.
AB  - Marine harbor sediments are frequently polluted with significant amount of
      polycyclic aromatic hydrocarbons (PAHs) some of which are naturally toxic,
      recalcitrant, mutagenic, and carcinogenic. To stimulate biodegradation of PAHs in
      PAH-contaminated sediments collected from near Gwangyang Bay, Korea, lactate was
      chosen as a supplementary carbonaceous substrate. Sediment packed into 600 ml air
      tight jar was either under no treatment condition or lactate amended condition
      (1%, w/v). Microbial community composition was monitored by bacteria-specific and
      archaea-specific PCR-terminal restriction fragment length polymorphism (T-RFLP),
      in addition to measuring the residual PAH concentration. Results showed that
      lactate amendment enhanced biodegradation rate of PAHs in the sediment by 4 to 8
      times, and caused a significant shift in archaebacterial community in terms of
      structure and diversity with time. Phylogenetic analysis of 23 archaeal clones
      with distinctive RFLP patterns among 288 archaeal clones indicated that majority
      of the archaeal members were closest to unculturable environmental rDNA clones
      from hydrocarbon-contaminated and/or methanogenesis-bearing sediments. Lactate
      amendment led to the enrichment of some clones that were most closely related to
      PAH-degrading Methanosarcina species. These results suggest a possible
      contribution of methanogenic community to PAH degradation and give us more
      insights on how to effectively remediate PAH-contaminated sediments.

PMID- 19107390
TI  - Dark septate endophyte (DSE) fungi isolated from metal polluted soils: their
      taxonomic position, tolerance, and accumulation of heavy metals in vitro.
AB  - To understand the possible role of the plant root associated fungi on metal
      tolerance, their role in the uptake of heavy metals and the potential transfer of
      these metal ions to the plant, three strains of dark septate endophytic (DSE)
      fungi were isolated from a waste smelter site in southwest China, and one strain
      was isolated from a non-contaminated site. According to molecular phylogenetic
      analysis of the ITS 1-5.8S rDNA-ITS 2 gene regions and morphological
      characteristics, one is identified as Exophiala pisciphila, and the other three
      are non-sporulating fungi under the experiment condition with the nearest
      phylogenetic affinities to the Thysanorea papuana strain EU041814. Tolerance and
      accumulation abilities of the three DSE strains for metals were investigated in
      liquid culture. Minimum inhibitory concentrations (MIC) of Pb, Zn, and Cd were
      determined. It was demonstrated that the tolerance of the DSE strains varied
      between metal species and strains. The E. pisciphila strain is able to accumulate
      lead and cadmium over 20% and 5% of dry weight of biomass, respectively. Partial
      of the sequestrated metals can be washed with CaCh. Morphological and enzyme
      activity changes taking place in the presence of excessive Pb, Cd, and/or Zn also
      indicate that the mechanism of heavy metal tolerance and accumulation of the DSE
      strains would be a complex process. The findings indicated promising tolerance
      and accumulation of the DSE strains with potential values in metal cycling and
      restoration of soil and water system.

PMID- 19107391
TI  - Prevalence of tetracycline resistance genes in Greek seawater habitats.
AB  - The presence of selected tetracycline resistance (TcR) genes was studied in
      different Greek seawater habitats, originated from wastewater treatment
      facilities, fishfarm, and coastal environments. The methods employed included
      assessment of the presence of twelve gene clusters by PCR, followed by
      hybridization with specific probes, in habitat extracted DNA, Tc(R) bacteria, and
      exogenous isolated plasmids conferring TcR. The direct DNA-based analysis showed
      that tet(A) and tet(K) genes were detected in all habitats, whilst tet(C) and
      tet(E) were present in fishfarm and wastewater effluent samples and tet(M) was
      detected in fish-farm and coastal samples. Resistance genes tet(h), tet(C),
      tet(K), and tet(M) were detected in 60 of the 89 isolates screened. These
      isolates were identified by fatty acid methyl ester analysis (FAME) as
      Stenotrophomonas, Acinetobacter, Pseudomonas, Bacillus, and Staphylococcus
      strains. The presence of the TcR genes in 15% of the bacterial isolates coincided
      with the presence of IncP plasmids. A habitat-specific dissemination of IncP
      alpha plasmids in wastewater effluent isolates and of IncP beta plasmids in
      fishfarm isolates was observed. Exogenous isolation demonstrated the presence of
      plasmids harbouring Tc(R) genes in all the habitats tested. Plasmids were shown
      to carry tet(h), tet(C), tet(E), and tet(K) genes. It is concluded that TcR genes
      are widespread in the seawater habitats studied and often occur on broad host
      range plasmids that seem to be well disseminated in the bacterial communities.

PMID- 19107392
TI  - Enhancement of growth and yield of tomato by Rhodopseudomonas sp. under
      greenhouse conditions.
AB  - A greenhouse test was carried out to examine the effects on tomato growth of
      application of purple non-sulfur bacterium Rhodopseudomonas sp. which had
      enhanced germination and growth of tomato seed under axenic conditions. The shoot
      length of tomato plant inoculated by Rhodopseudomonas sp. KL9 increased by 34.6%
      compared to that of control in 8 weeks of cultivation. During the same period,
      this strain increased 120.6 and 78.6% of dry weight of shoot and root of tomato
      plants, respectively. The formation ratio of tomato fruit from flower was also
      raised by inoculation of KL9. In addition, Rhodopseudomonas sp. KL9 treatment
      enhanced the fresh weight and lycopene content in the harvested tomato fruits by
      98.3 and 48.3%, respectively compared to those of the uninoculated control. When
      the effect on the indigenous bacterial community and fate of the inoculated
      Rhodopseudomonas sp. KL9 were monitored by denaturing gradient gel
      electrophoresis analysis, its application did not affect the native bacterial
      community in tomato rhizosphere soil, but should be repeated to maintain its
      population size. This bacterial capability may be applied as an environment
      friendly biofertilizer to cultivation of high quality tomato and other crops
      including lycopene-containing vegetables and fruits.

PMID- 19107393
TI  - Diversity of bacterial community in freshwater of Woopo wetland.
AB  - Diversity of bacterial community in water layer of Woopo wetland was
      investigated. Cultivable bacterial strains were isolated by the standard dilution
      plating technique and culture-independent 16S rRNA gene clones were obtained
      directly from DNA extracts of a water sample. Amplified rDNA restriction analysis
      (ARDRA) was applied onto both of the isolates and 16S rRNA gene clones.
      Rarefaction curves, coverage rate and diversity indices of ARDRA patterns were
      calculated. Representative isolates and clones of all the single isolate/clone
      phylotype were partially sequenced and analyzed phylogenetically. Sixty-four and
      125 phylotypes were obtained from 203 bacterial isolates and 235 culture
      independent 16S rRNA gene clones, respectively. Bacterial isolates were composed
      of 4 phyla, of which Firmicutes (49.8%) and Actinobacteria (32.0%) were
      predominant. Isolates were affiliated with 58 species. Culture-independent 16S
      rRNA gene clones were composed of 8 phyla, of which Proteobacteria (62.2%),
      Actinobacteria (15.5%), and Bacteroidetes (13.7%) were predominant. Diversity of
      16S rRNA gene clones originated from cultivation-independent DNA extracts was
      higher than that of isolated bacteria.

PMID- 19107394
TI  - Biologically active and C-amidated hinnavinII-38-Asn produced from a Trx fusion
      construct in Escherichia coli.
AB  - The cabbage butterfly (Artogeia rapae) antimicrobial peptide hinnavinII as a
      member of cecropin family is synthesized as 37 residues in size with an amidated
      lysine at C-terminus and shows the humoral immune response to a bacterial
      invasion. In this work, a synthetic gene for hinnavinII-38-Asn (HIN) with an
      additional amino acid asparagine residue containing amide group at C-terminus was
      cloned into pET-32a(+) vector to allow expression of HIN as a Trx fusion protein
      in Escherichia coli strain BL21 (DE3) pLysS. The resulting expression level of
      the fusion protein Trx-HIN could reach 15-20% of the total cell proteins and more
      than 70% of the target proteins were in soluble form. The fusion protein could be
      purified successfully by HiTrap Chelating HP column and a high yield of 15 mg
      purified fusion protein was obtained from 80 ml E. coli culture. Recombinant HIN
      was readily obtained by enterokinase cleavage of the fusion protein followed by
      FPLC chromatography, and 3.18 mg pure active recombinant HIN was obtained from 80
      ml culture. The molecular mass of recombinant HIN determined by MALDI-TOF mass
      spectrometer is 4252.084 Da which matches the theoretical mass (4252.0 Da) of
      HIN. Comparing the antimicrobial activities of the recombinant hinnavinII with C
      amidated terminus to that without an amidated C-terminus, we found that the amide
      of asparagine at C-terminus of hinnavinII improved its potency on certain
      microorganism such as E. coli, Enterobacter cloacae, Bacillus megaterium, and
      Staphylococcus aureus.

PMID- 19107395
TI  - Stable expression and secretion of polyhydroxybutyrate depolymerase of Paucimonas
      lemoignei in Escherichia coli.
AB  - An efficient strategy for the expression and secretion of extracellular
      polyhydroxybutyrate depolymerase (PhaZ1) of Paucimonas lemoignei in Escherichia
      coli was developed by employing the signal peptide of PhaZ1 and a truncated ice
      nucleation protein anchoring motif (INPNC). Directly synthesized mature form of
      Phaz1 was present in the cytoplasm of host cells as inclusion bodies, while a
      construct containing Phaz1 and its own N-terminal signal peptide (PrePhaz1)
      enabled the secretion of active Phaz1 into the extracellular medium. However, the
      PrePhaz1 construct was harmful to the host cell and resulted in atypical growth
      and instability of the plasmid during the cultivation. In contrast, INPNC-Phaz1
      and INPNC-PrePhaz1 fusion constructs did not affect growth of host cells. INPNC
      Phaz1 was successfully displayed on the cell surface with its fusion form, but
      did not retain Phaz1 activity. In the case of INPNC-PrePhaz1, the initially
      synthesized fusion form was separated by precise cleavage of the signal peptide,
      and active Phaz1 was consequently released into the culture medium. The amount of
      Phaz1 derived from E. coli (INPNC-PrePhaz1) was almost twice as great as that
      directly expressed from E. coli (PrePhaz1), and was predominantly (approximately
      85%) located in the periplasm when cultivated at 22 degrees C but was efficiently
      secreted into the extracellular medium when cultivated at 37 degrees C.

PMID- 19107396
TI  - Cys-92, Cys-95, and the C-terminal 12 residues of the Vibrio harveyi ferric
      uptake regulator (Fur) are functionally inessential.
AB  - Ferric uptake regulator (Fur) is a global regulator involved in multiple aspects
      of bacterial life. The gene encoding the Vibrio harveyi Fur (FurVh) was cloned
      from a pathogenic V. harveyi strain isolated from diseased fish. FurVh shares 77%
      overall sequence identity with the Escherichia coli Fur (FurEc) and could
      complement a mutant of FurEc. Like FurEc, FurVh, possesses two cysteine residues
      at positions 92 and 95, yet unlike FurEc, in which these cysteine residues
      constitute part of the metal ion coordination site and hence are vital to the
      repressor activity, C92 and C95 of FurVh proved to be functionally inessential.
      Further study identified a Vibrio Fur signature sequence, which is preserved in
      all the ten Vibrio Fur proteins that have been discovered to date but in none of
      the non-vibrio Fur proteins. Site-directed and random mutation analyses of the
      signature residues, the cysteine residues, and seven highly charged amino acid
      residues indicated that D9, H32, C137, and K138 of FurVh are functionally
      important but D9, C137, and K138 can be replaced by more than one functional
      substitutes. Systematic deletion analysis demonstrated that the C-terminal 12
      residues of FurVh are functionally inessential. These results (i) indicated that
      the activation mechanism, or certain aspects of which, of FurVh is possibly
      different from that of FurEc; and (ii) suggested that it is not very likely that
      the C-terminal 12 residues play any significant role in the activation or
      stability of FurVh; and (iii) provided insights into the potential function of
      the local structure involving C137 and K138.

PMID- 19107397
TI  - Genus-specific distribution and pathovar-specific variation of the glycinecin R
      gene homologs in Xanthomonas genomes.
AB  - Xanthomonas axonopodis pv. glycines produces bacteriocins called glycinecin, and
      two glycinecin genes, glyA and glyR, were reported previously. In this paper, we
      describe genomic distribution and variation of the glyR gene revealed by
      extensive Southern hybridization analysis. In contrast to the glyA gene present
      only in X. axonopodis pv. glycines, the glyR gene was found to be distributed
      widely in all the pathovars of Xanthomas genus. It was also found that the glyR
      gene is a multigene family while the glyA is a single copy gene. Moreover, the
      copy number and the variation of the glyR multigene are unique to each pathovar
      of Xanthomonas. The uniqueness can be easily detected by the patterns resulted
      from Southern hybridization using the genomic digests. Thus, we suggest the glyR
      gene can serve as a useful genus-specific and pathovar-specific DNA marker for
      Xanthomonas. One of the glyR homologs was further isolated from X. axonopodis pv.
      glycines, and analyzed to be functional with strong inhibitory activity against
      several members of Xanthomonas.

PMID- 19107398
TI  - Detection of Pseudomonas aeruginosa carried a new array of gene cassettes within
      class 1 integron isolated from a teaching hospital in Nanjing, China.
AB  - We report here novel array of gene cassettes found in single variable region of
      class 1 integron disseminated in Pseudomonas aeruginosa isolated from a teaching
      hospital in Nanjing, Jiangsu Province, China. 29 of 47 (61%) P. aeruginosa
      strains were confirmed haboured class 1 integron, and all the positive strains
      have the same variable region confirmed by PCR and RFLP methods. The variable
      region contained an unreported order of four gene cassettes aac(6')-II-aadA13
      cmlA8-oxa-10. Of those, cmlA8 gene was a variant of cmlA5 encoding non-enzymatic
      protein which putatively confer resistance to chloramphenicol. Susceptibility
      testing revealed multidrug-resistant mechanisms were involved in the class 1
      integron positive clinical isolates. And the class 1 integron located on an about
      15 kb transferable plasmid was certified by conjugation experiment and plasmid
      DNA analysis. The macro restriction profile indicated those clinical strains were
      clonally related.

PMID- 19107399
TI  - Carbon source dependent dynamics of the Ccr4-Not complex in Saccharomyces
      cerevisiae.
AB  - We have investigated the composition of the conserved Ccr4-Not complex during
      different physiological states of Saccharomyces cerevisiae. Major changes were
      found, most notably in the expression of the central scaffold protein Not1p,
      which was strongly reduced in the absence of glucose. The low expression of Not1p
      was also evident from the inability of Pop2p to co-purify Not1p in cells from
      cultures lacking glucose. However, Not1p was still essential under conditions of
      low expression. The downregulation of Not1p indicates that many of the Ccr4-Not
      complex components are likely to have roles outside of the complex. We suggest
      that the use of different carbon sources will be a good starting point to unravel
      these functions.

PMID- 19107400
TI  - Organization of three rRNA (rrn) operons from Sphingobium chungbukense DJ77.
AB  - The nucleotide sequences of all three rRNA operons (rrnA, rrnB, and rrnC) of
      Sphingobium chungbukense DJ77 were determined. The three rrn operons have the
      same gene order (16S rRNA-tRNAIle-tRNAAla-23S rRNA-5S rRNA-tRNAfMet). The
      nucleotide sequences were identical over a 5,468 bp region spanning the 16S rRNA
      gene to the 5S rRNA gene. Variability was observed in the 5S rRNA-tRNAfMet spacer
      sequence of rrnB. The tRNAfMet gene sequences were identical except for two bases
      (T5794 and A5871 in rrnB, T5942 and A5956 in rrnA, but C5942 and G5956 in rrnC).
      Comparative sequence analyses of ribosomal RNA operons from DJ77 with those of
      the class Alphaproteobacteria, to which the genus Sphingobium belongs, reveal
      close evolutionary relationships with other members of the order
      Sphingomonadales.

PMID- 19107401
TI  - Molecular and phylogenetic characterization of Spodoptera litura granulovirus.
AB  - Baculovirus, Spodoptera litura granulovirus (SlGV) was isolated from the infected
      S. litura larvae, and was characterized. The granule of SlGV was ovoidal shape
      with an approximate size of 240 approximately 340 nmx 140 approximately 180 nm.
      Each granule contained one single rod-shape virion with a mean size of 180
      approximately 200 nmx20 approximately 40 nm. Restriction endonuclease fragment
      analysis estimated that the total genome size of SlGV is about 115 kb. Nucleotide
      sequence analysis of the granulin gene showed that the gene encodes 249 amino
      acids with a predicted molecular mass of 29 kDa. When the phylogenic relationship
      was analyzed using the nucleotide sequence of the granulin gene, SlGV was most
      closely related to Trichoplusia ni granulovirus (TnGV) and Xestia c-nigrum
      granulovirus (XcGV) which belong to Type I granulovirus.

PMID- 19107402
TI  - Molecular characterization of ORFs 2 to 7 of Korean porcine reproductive and
      respiratory syndrome virus (CA) and its protein expression by recombinant
      baculoviruses.
AB  - To determine the characteristics of the Korean porcine reproductive and
      respiratory syndrome virus (PRRSV), CA, which was isolated from the serum of an
      infected pig in 2006, we investigated the nucleotide sequence and expression of
      the structural ORFs (ORFs 2 to 7) using the bApGOZA system. We found that the
      structural ORFs 2 to 7 of CA consisted of 3188 nucleotides that were the same as
      those formed from VR-2332. Comparison of the CA with the other strains revealed
      nucleotide sequence identity ranging from 89.8 to 99.5%. To better understand the
      genetic relationships between other strains, phylogenetic analyses were
      performed. The CA strain was closely related to the other North American genotype
      strains but formed a distinct branch with high bootstrap support. Additionally,
      expression levels of the PRRSV proteins in insect cells were strong or partially
      weak. The results of this study have implications for both the taxonomy of PRRSV
      and vaccine development.

PMID- 19107403
TI  - Proteomic analysis of outer membrane proteins from Acinetobacter baumannii DU202
      in tetracycline stress condition.
AB  - Acinetobacter baumannii readily developed antimicrobial resistance to clinically
      available antibiotics. A. baumannii DU202 is a multi-drug resistant strain, and
      is highly resistant to tetracycline (MIC>1,024 micro/ml). The surface proteome of
      A. baumannii DU202 in response to the sub-minimal inhibitory concentration
      (subMIC) of tetracycline was analyzed by 2-DE/MS-MS and 1-DE/LC/MS-MS to
      understand the pathways that form barriers for tetracycline. Membrane expression
      of major outer membrane proteins (Omps) was significantly decreased in response
      to the subMIC of tetracycline. These Omps with sizes of 38, 32, 28, and 21 kDa
      were identified as OmpA38, OmpA32, CarO, and OmpW, respectively. However,
      transcription level of these Omps was not significantly changed. 1-DE/LC/MS-MS
      analysis of secreted proteins showed that OmpA38, CarO, OmpW, and other Omps were
      increasingly secreted at tetracycline condition. This result suggests that A.
      baumannii actively regulates the membrane expression and the secretion of Omps to
      overcome antibiotic stress condition.

PMID- 19107404
TI  - Enhancement of immunotherapeutic effects of HPV16E7 on cervical cancer by fusion
      with CTLA4 extracellular region.
AB  - Cervical cancer is caused by infection by high-risk human papillomavirus (HPV),
      especially HPV16. Limitations in current treatments of cervical cancers call for
      the development of new and improved immunotherapies. This study aims at
      investigating the efficacy of a novel vaccine consisting of modified HPV 16E7
      fused with human cytotoxic T-lymphocyte antigen 4 (CTLA4). The regions in HPV16
      E7 gene associated with its transformation and CTL-enhanced response were
      modified; the resultant HPV16mE7 was fused with extracellular region of CTLA4 to
      generate HPVml6E7-eCTLA4 fusion protein. Binding of this fusion protein to B7
      molecules expressed on antigen presenting-cells (APCs) was demonstrated. C57BL/6
      (H-2b) mice immunized with low dose of the fusion protein (10 microg) produced
      higher titer antibody and stronger specific CTL response, and expressed higher
      levels of IFN-gamma and IL-12, compared with those immunized with HPVml6E7 only
      or admixture of HPVml6E7 and CTLA4, or PBS; and were protected from lethal dose
      tumor challenge. Tumor growth was retarded and survival prolonged in mouse models
      with the fusion protein treatment. Our results demonstrate that fusion of HPV16
      E7 with eCTLA4 targeting APCs resulted in enhanced immunity, and that this fusion
      protein may be useful for improving the efficacy of immunotherapeutic treatments
      of cervical cancer and other HPV16 infection-associated tumors.

PMID- 19107405
TI  - Protective effect of polygoni cuspidati radix and emodin on Vibrio vulnificus
      cytotoxicity and infection.
AB  - Vibrio vulnificus, a good model organism of bacterial septicemia, causes fatal
      septicemia manifesting a fulminating course and a high mortality rate within
      days. In order to identify new natural substances preventing V. vulnificus
      infection, a plant library was screened for inhibiting cytotoxicity to host cells
      by using Trypan blue staining and LDH assay. We found that Polygoni Cuspidati
      Radix potently suppressed the acute death of HeLa and RAW264.7 cells in a dose
      dependent manner. Further studies revealed that Polygoni Cuspidati Radix
      inhibited V. vulnificus growth and survival in HI broth and seawater,
      respectively. We confirmed that Polygoni Cuspidati Radix contained high level of
      emodin by thin layer chromatography (TLC). Emodin showed direct antibacterial
      activity against V. vulnificus. In addition, emodin prevented the morphologic
      damages and acute death of HeLa cells caused from V. vulnificus. The safety of
      Polygoni Cuspidati Radix and emodin to host cells was confirmed by MTT assay.
      Polygoni Cuspidati Radix and emodin protected mice from V. vulnificus infection.

PMID- 19107406
TI  - Inhibitory effect of methyl gallate and gallic acid on oral bacteria.
AB  - This study examined the ability of methyl gallate (MG) and gallic acid (GA), the
      main compounds of gallo-tannins in Galla Rhois, to inhibit the proliferation of
      oral bacterial and the in vitro formation of Streptococcus mutans biofilms. The
      antimicrobial activities of these compounds were evaluated in vitro using the
      broth microdilution method and a beaker-wire test. Both MG and GA had inhibitory
      effects on the growth of cariogenic (MIC<8 mg/ml) and periodontopathic bacteria
      (MIC=1 mg/ml). Moreover, these compounds significantly inhibited the in vitro
      formation of S. mutans biofilms (MG, 1 mg/ml; GA, 4 mg/ml; P<0.05). MG was more
      effective in inhibiting bacterial growth and the formation of S. mutans biofilm
      than GA. In conclusion, MG and GA can inhibit the growth of oral pathogens and S.
      mutans biofilm formation, and may be used to prevent the formation of oral
      biofilms.

PMID- 19107407
TI  - The SUMO system: an overview.
AB  - Post-translational modification by SUMO is now recognized as an important
      regulatory method employed by the cell to reversibly modulate the activity,
      stability, or localization of intracellular proteins. A dedicated enzymatic
      machinery is involved in the processing, attachment, and removal of the modifier
      with high selectivity. SUMO modification generally alters the properties of the
      modified target by influencing-either positively or negatively-its interactions
      with other cellular factors. As a consequence, the SUMO system contributes to the
      regulation of numerous biological pathways, ranging from nucleocytoplasmic
      transport to the repression of transcriptional activity and the maintenance of
      genome stability by its influence on DNA recombination and repair. This chapter
      gives a brief overview over the enzymes of the SUMO system, its regulation, and
      its functions.

PMID- 19107408
TI  - Identification of SUMO target proteins by quantitative proteomics.
AB  - The identification of target proteins for small ubiquitin-like modifiers (SUMOs)
      is a critical step towards a detailed understanding of the cellular functions of
      SUMOs. Substrate protein identification for SUMOs is hampered by the low
      abundance of SUMO targets, the finding that only a small fraction of these target
      proteins is sumoylated, and the high activity of deconjugating enzymes.
      Quantitative proteomics is a powerful tool to overcome these challenges, because
      it allows discrimination between contaminating proteins in SUMO-enriched
      preparations and true target proteins. In this chapter, the methodological
      details of the application of stable isotope labeling of amino acids in cell
      culture (SILAC) for the identification of target proteins for SUMOs are
      described. In addition to steady state sumoylation, the sumoylated proteome
      undergoes dynamic rearrangements in response to a diverse array of stimuli. SILAC
      also allows the study of sumoylation dynamics in response to these stimuli.

PMID- 19107409
TI  - Identification of SUMO-conjugated proteins and their SUMO attachment sites using
      proteomic mass spectrometry.
AB  - The covalent modification of cellular factors by the small ubiquitin-like
      modifier (SUMO) has emerged as a key regulatory pathway for many biological
      processes. One recent advance in the field of SUMO modification that has provided
      important insights into SUMO-mediated regulatory networks is the ability to use
      proteomic mass spectrometry to identify the substrates of SUMO modification as
      well as their sites of conjugation (1-10). In this chapter, we describe a global
      strategy for affinity purifying and identifying a broad spectrum of SUMO
      conjugated proteins and a focused approach for purifying a selected SUMO target
      and mapping its SUMO attachment site(s). Although both methods were initially
      developed for use in S. cerevisiae, they can be readily adapted to study the SUMO
      pathway in higher eukaryotes.

PMID- 19107410
TI  - Identification of SUMO targets through in vitro expression cloning.
AB  - Covalent modification of proteins by small ubiquitin-like modifier (SUMO)
      regulates diverse cellular processes. While many SUMO substrates are identified
      through individual efforts, affinity-based approaches followed by mass
      spectrometry are also used to identify in vivo SUMO substrates in yeast and in
      mammals. Because of low steady-state levels of sumoylation and biases towards
      abundant targets, identifying sumoylated proteins in vivo can be challenging. The
      in vitro expression cloning (IVEC) method for SUMO target identification
      circumvents these challenges and complements the affinity-based approaches. IVEC
      allows for immediate validation and analysis of substrates through in vitro
      reconstitution. Furthermore, this method can be easily adapted to identify
      substrates of specific SUMO ligases.

PMID- 19107411
TI  - Enhanced detection of in vivo SUMO conjugation by Ubc9 fusion-dependent
      sumoylation (UFDS).
AB  - The bottleneck in studying protein sumoylation-the conjugation of the small
      ubiquitin-like modifier (SUMO)-is the detection of the low level of in vivo
      sumoylated proteins. The Ubc9 fusion-directed sumoylation (UFDS) system strongly
      enhances the in vivo sumoylation of a substrate protein at its specific
      sumoylation site. UFDS utilizes an expression plasmid for the protein of interest
      fused to the SUMO-conjugating enzyme Ubc9. When expressed in HEK293, COS-7, HeLa,
      or CHO cells, the fused target protein is conjugated with endogenous or
      coexpressed SUMO at its native sumoylation sites. This sumoylation requires
      neither SUMO ligase nor any extracellular stimulation and is easily detectable by
      fusion protein- or Ubc9-specific Western blotting with commercially available
      antibodies.

PMID- 19107412
TI  - In vivo detection and characterization of sumoylation targets in Saccharomyces
      cerevisiae.
AB  - Ni-NTA affinity chromatography under denaturing conditions has proven to be a
      powerful method for the isolation of SUMO conjugates from total cell extracts, as
      it minimizes deconjugation and excludes noncovalent interactions. This chapter
      describes the use of both His-tagged SUMO and a His-tagged target protein for the
      characterization of the sumoylation process in the budding yeast Saccharomyces
      cerevisiae. Two well-studied model substrates, the septin Cdc3 and the
      replication clamp protein PCNA, are used as examples, but the protocol can easily
      be adapted to other targets and organisms.

PMID- 19107413
TI  - Identification of SUMO-interacting proteins by yeast two-hybrid analysis.
AB  - This chapter will discuss various adaptations of the yeast two-hybrid method for
      analyzing protein interactions that can be used to identify small ubiquitin
      related modifier (SUMO) interacting proteins and to determine the nature of the
      SUMO-protein interactions that occur. SUMO binds to a protein in two different
      ways: covalently and noncovalently. In a covalent interaction an isopeptide bond
      forms between the glycine residue at the C terminus of the mature SUMO and a
      lysine side-chain on the substrate protein. Alternatively, SUMO can interact
      noncovalently with another protein, usually via insertion of a beta strand from a
      substrate SUMO-interacting motif (SIM) into a hydrophobic groove next to the SUMO
      beta2 strand. By mutating either the C-terminal diglycine motif or amino acids
      within the beta2 strand of SUMO, these respective interactions can be abolished.
      The expression of the two-hybrid SUMO constructs with either of these mutations
      can help distinguish the type of interaction that occurs between a SUMO and a
      given protein. Sumoylation can be verified by independent methods, such as a SUMO
      mobility shift assay. Finally, the chapter will compare the two-hybrid approach
      with mass spectrometric analysis as a means of identifying SUMO-interacting
      proteins.

PMID- 19107414
TI  - Identification of SUMO-binding motifs by NMR.
AB  - Post-translational modification by the small ubiquitin-like modifier (SUMO)
      family of proteins is an important cellular regulatory mechanism, and in recent
      years has been found to be involved in a large and diverse set of signaling
      pathways. Most of these SUMO-dependent functions appear to be mediated by the
      interaction between SUMO attached to the modified proteins and a "SUMO-binding
      motif" (SBM or SIM) on receptor proteins. Nuclear magnetic resonance (NMR)
      studies were instrumental in the identification of this SUMO-binding motif, and
      reveal that, depending on the sequence context, this motif can bind to SUMO in
      two opposing orientations. In this paper, we provide an overview of how NMR
      methods can be used to identify such short conserved binding motifs and
      structurally characterize their interaction with target proteins. These
      experiments are complementary to traditional biochemical methods and are
      applicable to the identification of other SUMO-binding motifs and to the studies
      of other ubiquitin-like modification systems.

PMID- 19107415
TI  - Regulation of transcription factor activity by SUMO modification.
AB  - Post-translational modification by SUMO is an important mechanism to regulate
      transcription. Sumoyla-tion has diverse effects on substrate activity, but in
      most cases reported to date sumoylation of transcription factors correlated with
      transcriptional repression. Here we describe general strategies to address how
      post-translational modification by SUMO regulates the activity of a DNA-binding
      transcription factor.

PMID- 19107416
TI  - Characterization of the effects and functions of sumoylation through rapamycin
      mediated heterodimerization.
AB  - Post-translational modification of proteins, such as phosphorylation,
      ubiquitination, and SUMO modification, is an important means of regulating a
      variety of cellular activities. SUMOs (Small Ubiquitin related Modifiers) are
      covalently conjugated to lysine residues of many proteins by a mechanism that
      parallels ubiquitination (1). The effects of sumoylation, however, are distinct
      from ubiquitination. Sumoylation does not directly control protein stability, but
      regulates proteins through various mechanisms that include modulation of protein
      protein interactions, protein-nucleic acid interactions, subcellular protein
      localization, and enzymatic activity (1-4). There are many examples, however,
      where the molecular bases for the effects of sumoylation on protein function and
      on cellular processes remain unclear. Here, we outline the use of an inducible
      and reversible sumoylation system, based on rapamycin heterodimerization, as a
      novel tool to characterize the functions of sumoylation in mammalian cells.

PMID- 19107417
TI  - Purification of SUMO conjugating enzymes and kinetic analysis of substrate
      conjugation.
AB  - SUMO conjugation to protein substrates requires the concerted action of a
      dedicated E2 ubiquitin conjugation enzyme (Ubc9) and associated E3 ligases.
      Although Ubc9 can directly recognize and modify substrate lysine residues that
      occur within a consensus site for SUMO modification, E3 ligases can redirect
      specificity and enhance conjugation rates during SUMO conjugation in vitro and in
      vivo. In this chapter, we will describe methods utilized to purify SUMO
      conjugating enzymes and model substrates which can be used for analysis of SUMO
      conjugation in vitro. We will also describe methods to extract kinetic parameters
      during E3-dependent or E3-independent substrate conjugation.

PMID- 19107418
TI  - Performing in vitro sumoylation reactions using recombinant enzymes.
AB  - Sumoylation of proteins in vitro has evolved as an indispensable tool for the
      functional analysis of this post-translational modification. In this article we
      present detailed protocols for bacterial production of mammalian proteins
      necessary to perform in vitro sumoylation reactions, namely the E1 activating
      enzyme Aos1/Uba2 (SAE1/SAE2), the E2 conjugating enzyme Ubc9, SUMO-1 (identical
      protocols can be used for SUMO-2/3), and the catalytic domain of the E3 ligase
      RanBP2/Nup358. Two alternative procedures are described for the E1 enzyme, one
      depending on co-expression of His-Aos1 and untagged Uba2, and a second protocol
      for separate expression of His-Aos1 and Uba2-His and subsequent reconstitution of
      the active dimer. Two example conditions for in vitro sumoylation of RanGAP1 and
      Sp100 in the absence or presence of the SUMO E3 ligase RanBP2, respectively, are
      provided. Both protocols can be adapted easily to test in vitro conjugation of
      other target proteins and/or E3 ligases.

PMID- 19107419
TI  - Preparation of sumoylated substrates for biochemical analysis.
AB  - Covalent modification of proteins with SUMO (small ubiquitin related modifier)
      affects many cellular processes like transcription, nuclear transport, DNA repair
      and cell cycle progression. Although hundreds of SUMO targets have been
      identified, for several of them the function remains obscure. In the majority of
      cases sumoylation is investigated via "loss of modification" analysis by mutating
      the relevant target lysine. However, in other cases this approach is not
      successful since mapping of the modification site is problematic or mutation does
      not cause an obvious phenotype. These latter cases ask for different approaches
      to investigate the target modification. One possibility is to choose the opposite
      approach, a "gain in modification" analysis by producing both SUMO modified and
      unmodified protein in vitro and comparing them in functional assays. Here, we
      describe the purification of the ubiquitin conjugating enzyme E2-25K, its in
      vitro sumoylation with recombinant enzymes and the subsequent separation and
      purification of the modified and the unmodified forms.

PMID- 19107420
TI  - Strategies for the expression of SUMO-modified target proteins in Escherichia
      coli.
AB  - We previously described the establishment of a binary vector system that allows
      co-expression of SUMO conjugation enzymes and a target protein of interest,
      leading to efficient SUMO modification and the production of a large amount of
      recombinant SUMO-modified proteins in Escherichia coli. The advantages of this E.
      coli expression/modification approach include scalability of experiments, low
      cost, fast growth, and a lack of proteases that cleave the isopeptide linkage
      between SUMO and the target protein. Thus, this E. coli method provides a useful
      alternative to authentic SUMO modification assays, such as in vitro SUMO
      conjugation and in vivo SUMO modification using baculovirus or mammalian cell
      culture, that are usually complicated, time-consuming and expensive.

PMID- 19107421
TI  - Preparation of SUMO proteases and kinetic analysis using endogenous substrates.
AB  - SUMO proteases catalyze two reactions, deconjugation of SUMO from substrates and
      processing of precursor SUMO isoforms to prepare SUMO for conjugation. The SUMO
      protease family includes two members in yeast (Ulp1 and Ulp2) and as many as six
      members in human (SENP1-3, SENP5-7). SENP/Ulp proteases each contain conserved C
      terminal domains that catalyze protease activity. The C-terminal protease domains
      exhibit unique specificities during SUMO processing and deconjugation in vitro.
      While there are many available reagents to assess these activities, including
      fusion proteins and chemically modified SUMO isoforms, our studies have indicated
      that the composition of substrates C-terminal to the scissile bond can
      substantively influence the activity of the protease. As such, we have relied
      extensively on assays that utilize endogenous substrates, namely wild-type SUMO
      precursors and SUMO conjugated substrates. In this chapter, we will describe
      methodological details for purification and characterization of SUMO precursors,
      SUMO conjugated substrates, and SUMO proteases. We will also describe methods for
      kinetic analysis of SUMO deconjugation and maturation using endogenous
      substrates.

PMID- 19107422
TI  - An in vitro FRET-based assay for the analysis of SUMO conjugation and
      isopeptidase cleavage.
AB  - To measure rates of sumoylation and isopeptidase cleavage in vitro, we developed
      an enzyme assay that is based on fluorescence resonance energy transfer (FRET).
      FRET is a process by which the excited state energy of a fluorescent donor
      molecule is transferred to an acceptor molecule. Efficient energy transfer
      requires very close proximity, and can therefore be used as a read-out for
      covalent and non-covalent protein interactions. The assay described here uses
      bacterially expressed and purified YFP-SUMO-1 and CFP-RanGAP1 as model substrates
      that are covalently coupled in the presence of recombinant SUMO E1 and E2 enzymes
      and ATP. Reactions of 25 microl volume, set up in 384-wells plates, give
      sufficient signal for analysis. Consequently, this assay requires very low
      amounts of recombinant proteins and allows measurement of time courses in high
      throughput format.

PMID- 19107423
TI  - FRET-based in vitro assays for the analysis of SUMO protease activities.
AB  - In humans cells three SUMO paralogues (SUMO-1, SUMO-2 and SUMO-3) and six SUMO
      specific proteases (SENP1-SENP3 and SENP5-SENP7) are expressed. Together the SUMO
      proteases perform three distinct functions. They: (1) process the immature pro
      SUMO proteins into the active forms, (2) remove SUMO molecules conjugated to
      protein targets, and (3) depolymerise SUMO conjugated within polymeric chains. By
      regulating these processes the SENPs play a crucial role in regulating the
      sumoylation state of target proteins in cells, and therefore are academically and
      pharmacologically interesting enzymes. Gel-based techniques for SENP analysis are
      well established and can be used for many applications, but their laborious
      methodology makes them cumbersome tools for kinetic analysis or inhibitor
      screening. Therefore in vitro FRET-based assays have been developed to test the
      three major functions of the SENPs. These use fluorescent protein fusions of the
      SUMOs, and together facilitate high-throughput, real-time analysis of the three
      major SUMO protease activities.

PMID- 19107424
TI  - Detection and characterization of SUMO protease activity using a sensitive enzyme
      based reporter assay.
AB  - In this chapter we describe a novel, sensitive, homogenous high throughput
      reporter-based in vitro assay for SUMO protease activity developed by Progenra,
      Inc. A reporter construct was created by fusing His(6)-tagged small ubiquitin
      like modifier (SUMO) to the amino terminus of the reporter enzyme phospholipase
      A(2) (PLA(2)). Following cleavage by a member of the sentrin specific proteases
      (SENPs), free PLA(2) is able to turn over its substrate, resulting in the release
      of a fluorescent product which is readily quantifiable using a fluorimeter or a
      fluorescence plate reader. The utility of this SUMO-CHOP-Reporter assay platform
      is demonstrated by its ability to determine K(m) values and to characterize
      inhibitors of SUMO proteases.

PMID- 19107425
TI  - Inhibition of the SUMO pathway by Gam1.
AB  - We have previously demonstrated that Gam1, an avian adenoviral protein inhibits
      sumoylation. By counteracting the SUMO pathway, Gam1 has a significant impact on
      virus-infected cells, but in isolation the inhibitory effects of the Gam1 protein
      can be exploited to intentionally manipulate the SUMO system in vivo or in vitro.
      Here we discuss in detail the techniques we use to inhibit the SUMO pathway using
      the Gam1 protein.

PMID- 19107426
TI  - SUMO fusion technology for enhanced protein production in prokaryotic and
      eukaryotic expression systems.
AB  - In eukaryotic cells, the reversible attachment of small ubiquitin-like modifier
      (SUMO) protein is a post-translational modification that has been demonstrated to
      play an important role in various cellular processes. Moreover, it has been found
      that SUMO as an N-terminal fusion partner enhances functional protein production
      in prokaryotic and eukaryotic expression systems, based upon significantly
      improved protein stability and solubility. Following the expression and
      purification of the fusion protein, the SUMO-tag can be cleaved by specific
      (SUMO) proteases via their endopeptidase activity in vitro to generate the
      desired N-terminus of the released protein partner. In addition to its
      physiological relevance in eukaryotes, SUMO can, thus, be used as a powerful
      biotechnological tool for protein expression in prokaryotic and eukaryotic cell
      systems.In this chapter, we will describe the construction of a fusion protein
      with the SUMO-tag, its expression in Escherichia coli, and its purification
      followed by the removal of the SUMO-tag by a SUMO-specific protease in vitro.

PMID- 19107427
TI  - Environmental and occupational risk factors for lung cancer.
AB  - Lung cancer is the world's leading cause of cancer death. It is primarily due to
      the inhalation of carcinogens and highly accessible to prevention by diminishing
      exposures to lung carcinogens. Most important will be the complete cessation of
      exposure to cigarette smoke (first and second hand) and to asbestos. Two
      environmental exposures--radon in homes and arsenic in drinking water--cannot be
      totally avoided, but people in certain geographical regions would greatly benefit
      from a reduction in exposure magnitude. And last but not least, workers all over
      the world deserve that preventive measures at the workplace are observed with
      regard to exposures, such as arsenic, beryllium, bis-chloromethyl ether (BCME),
      cadmium, chromium, polycyclic aromatic hydrocarbons (PAHs), and nickel.

PMID- 19107428
TI  - Lifestyle, genes, and cancer.
AB  - It is estimated that almost 1.5 million people in the USA are diagnosed with
      cancer every year. However, due to the substantial effect of modifiable lifestyle
      factors on the most prevalent cancers, it has been estimated that 50% of cancer
      is preventable. Physical activity, weight loss, and a reduction in alcohol use
      can strongly be recommended for the reduction of breast cancer risk. Similarly,
      weight loss, physical activity, and cessation of tobacco use are important
      behavior changes to reduce colorectal cancer risk, along with the potential
      benefit for the reduction of red meat consumption and the increase in folic acid
      intake. Smoking cessation is still the most important prevention intervention for
      reducing lung cancer risk, but recent evidence indicates that increasing physical
      activity may also be an important prevention intervention for this disease. The
      potential benefit of lifestyle change to reduce prostate cancer risk is growing,
      with recent evidence indicating the importance of a diet rich in tomato-based
      foods and weight loss. Also, in the cancers for which there are established
      lifestyle risk factors, such as physical inactivity for breast cancer and obesity
      for colorectal cancer, there is emerging information on the role that genetics
      plays in interacting with these factors, as well as the interaction of
      combinations of lifestyle factors. Integration of genetic information into
      lifestyle factors can help to clarify the causal relationships between lifestyle
      and genetic factors and assist in better identifying cancer risk, ultimately
      leading to better-informed choices about effective methods to enhance health and
      prevent cancer.

PMID- 19107429
TI  - Energy balance, physical activity, and cancer risk.
AB  - This chapter posits that cancer is a complex and multifactorial process as
      demonstrated by the expression and production of key endocrine and steroid
      hormones that intermesh with lifestyle factors (physical activity, body size, and
      diet) in combination to heighten cancer risk. Excess weight has been associated
      with increased mortality from all cancers combined and for cancers of several
      specific sites. The prevalence of obesity has reached epidemic levels in many
      parts of the world; more than 1 billion adults are overweight with a body mass
      index (BMI) exceeding 25. Overweight and obesity are clinically defined
      indicators of a disease process characterized by the accumulation of body fat due
      to an excess of energy intake (nutritional intake) relative to energy expenditure
      (physical activity). When energy intake exceeds energy expenditure over a
      prolonged period of time, the result is a positive energy balance (PEB), which
      leads to the development of obesity. This physical state is ideal for
      intervention and can be modulated by changes in energy intake, expenditure, or
      both. Nutritional intake is a modifiable factor in the energy balance-cancer
      linkage primarily tested by caloric restriction studies in animals and the effect
      of energy availability. Restriction of calories by 10 to 40% has been shown to
      decrease cell proliferation, increasing apoptosis through anti-angiogenic
      processes. The potent anticancer effect of caloric restriction is clear, but
      caloric restriction alone is not generally considered to be a feasible strategy
      for cancer prevention in humans. Identification and development of preventive
      strategies that "mimic" the anticancer effects of low energy intake are
      desirable. The independent effect of energy intake on cancer risk has been
      difficult to estimate because body size and physical activity are strong
      determinants of total energy expenditure. The mechanisms that account for the
      inhibitory effects of physical activity on the carcinogenic process are reduction
      in fat stores, activity related changes in sex-hormone levels, altered immune
      function, effects in insulin and insulin-like growth factors, reduced free
      radical generation, and direct effect on the tumor. Epidemiologic evidence posits
      that the cascade of actions linking overweight and obesity to carcinogenesis are
      triggered by the endocrine and metabolic system. Perturbations to these systems
      result in the alterations in the levels of bioavailable growth factors, steroid
      hormones, and inflammatory markers. Elevated serum concentrations of insulin lead
      to a state of hyperinsulinemia. This physiological state causes a reduction in
      insulin-like growth factor-binding proteins and promotes the synthesis and
      biological activity of insulin-like growth factor (IGF)-I, which regulates
      cellular growth in response to available energy and nutrients from diet and body
      reserves. In vitro studies have clearly established that both insulin and IGF-I
      act as growth factors that promote cell proliferation and inhibit apoptosis.
      Insulin also affects on the synthesis and biological availability of the male and
      female sex steroids, including androgens, progesterone, and estrogens.
      Experimental and clinical evidence also indicates a central role of estrogens and
      progesterone in regulating cellular differentiation, proliferation, and apoptosis
      induction. Hyperinsulinemia is also associated with alterations in molecular
      systems such as endogenous hormones and adipokines that regulate inflammatory
      responses. Obesity-related dysregulation of adipokines has the ability to
      contribute to tumorigenesis and tumor invasion via metastatic potential. Given
      the substantial level of weight gain in industrialized countries in the last two
      decades, there is great interest in understanding all of the mechanisms by which
      obesity contributes to the carcinogenic process. Continued focus must be directed
      to understanding the various relationships between specific nutrients and dietary
      components and cancer cause and prevention. A reductionist approach is not
      sufficient for the basic biological mechanisms underlying the effect of diet and
      physical activity on cancer. The joint association between energy balance and
      cancer risk are hypothesized to share the same underlying mechanisms, the
      amplification of chemical mediators that modulate cancer risk depending on the
      responsiveness to those hormones to the target tissue of interest. Disentangling
      the connection between obesity, the insulin-IGF axis, endogenous hormones,
      inflammatory markers, and their molecular interaction is vital.

PMID- 19107430
TI  - Genetic epidemiology studies in hereditary non-polyposis colorectal cancer.
AB  - Genetic epidemiology studies in hereditary non-polyposis colorectal cancer
      (HNPCC) have the potential to radically improve assessment of disease risk such
      that more individualised information can be provided to patients susceptible to
      developing disease. Studies of HNPCC initially focused on disease associations
      and the definition of the disease and its association with different cancers
      within the context of an inherited predisposition. With the identification of the
      genetic basis of HNPCC, new insights into the disease have been forthcoming and
      many advances in our understanding have been made. There have been many reports
      examining potential modifier genes in HNPCC, yet the results remain controversial
      as many findings have not been replicated and therefore no clear consensus as to
      the role of specific modifier genes has been reached. This review focuses on some
      of the factors associated with disease risk in HNPCC and where some of the
      difficulties lie in assessing the value of genetic epidemiology studies in this
      disorder.

PMID- 19107431
TI  - Parental smoking and childhood leukemia.
AB  - Childhood leukemia is the most common cancer among children, representing 31% of
      all cancer cases occurring in children younger than the age of 15 years in the
      USA. There are only few known risk factors of childhood leukemia (sex, age, race,
      exposure to ionizing radiation, and certain congenital diseases, such as Down
      syndrome and neurofibromatosis), which account for only 10% of the childhood
      leukemia cases. Several lines of evidence suggest that childhood leukemia may be
      more due to environmental rather than genetic factors, although genes may play
      modifying roles. Human and animal studies showed that the development of
      childhood leukemia is a two-step process that requires a prenatal initiating
      event(s) plus a postnatal promoting event(s). Despite a substantial public health
      effort to reduce cigarette smoking, a large proportion of the US and world
      population still smoke. Tobacco smoke contains at least 60 known human or animal
      carcinogens, with the major chemical classes being volatile hydrocarbons,
      aldehydes, aromatic amines, polycyclic aromatic hydrocarbons, and nitrosamines;
      among these chemicals, only benzene is an established leukemogen, although other
      chemicals in the tobacco could interact with one another in a complex way to
      jointly attain a significant carcinogenic effect on the development of leukemia.
      Although tobacco smoke is an established risk factor for adult myeloid leukemia,
      the studies of association between parental smoking and childhood leukemia have
      produced inconsistent results. The majority of the studies on maternal smoking
      and childhood leukemia did not find a significant positive association and some
      even reported an inverse association. In contrast to studies of maternal smoking,
      studies of paternal smoking and childhood leukemia reported more positive
      associations but only by less than half of the studies. Future directions to be
      considered for improving the study of parental smoking and childhood leukemia
      are: 1) consider all sources of benzene exposure in addition to smoking,
      including occupational exposure and traffic exhausts; 2) childhood leukemia is a
      heterogeneous disease and epidemiologic studies of childhood leukemia can be
      greatly improved by grouping childhood leukemia into more homogeneous groups by
      molecular techniques (e.g., structural and numerical chromosomal changes); and 3)
      assess gene-environment interaction. It is hoped that through the continual
      effort, more will be uncovered regarding the causes of childhood leukemia. In the
      meantime, more effort should be spent on educating the parents to quit smoking,
      because parental smoking is known to affect many childhood diseases (e.g.,
      asthma, respiratory tract infection, and otitis media) that are much more
      prevalent than childhood leukemia.

PMID- 19107432
TI  - Lung cancer and exposure to metals: the epidemiological evidence.
AB  - Exposure to metallic compounds is ubiquitous, with its widespread use in industry
      and its presence, mostly in trace amounts, in the environment. This paper reviews
      the epidemiologic evidence of the relation between lung cancer and exposure to
      metallic compounds by building on and updating the corresponding International
      Agency for Research on Cancer (IARC) assessments. Given that most of the well
      identified human populations with given metal exposure are in occupational
      settings, this review is mostly based on results in occupational epidemiology.
      The epidemiological evidence is shortly reviewed for accepted carcinogens:
      chromium, nickel, beryllium, cadmium, arsenic, and silicon, highlighting what is
      still unclear. We then review in more detail metals for which the evidence is
      less clear: lead, titanium, iron, and cobalt. There is scarce evidence for the
      human carcinogenicity of titanium. Exposure to titanium dioxide is associated
      with lung cancer excesses in one large study, but this excess may be due to
      confounders. The evidence for lead is contradictory. The lung cancer risk is
      presented as a function of a post hoc exposure ranking but no dose-response
      relationship is found. A weak but consistent lung cancer excess in many
      populations exposed to iron oxides but it is not possible to state on causality.
      Finally the evidence in the hard metal industry is presented, which suggests a
      possible carcinogenic effect of cobalt in presence of tungsten carbide. A short
      discussion presents the limitations of epidemiology in assessing the
      carcinogenicity of metals.

PMID- 19107433
TI  - Breast cancer and the role of exercise in women.
AB  - Cancer of the breast is a significant health problem for women from the time of
      diagnosis through the treatment and survivorship trajectory. The disease and
      treatments are an assault to a woman's body, resulting in sequelae that can be
      debilitating. Although women diagnosed with breast cancer are living longer,
      concerns about functional limitations, recurrence, and survival remain paramount.
      Physical activity and exercise are preventative and rehabilitative measures that
      can be employed at various points along the breast cancer trajectory. Current
      research supports the beneficial role that physical activity and exercise play in
      reducing the risk for developing breast cancer and preventing or attenuating
      disease and treatment-related impairments.

PMID- 19107434
TI  - Energy intake, physical activity, energy balance, and cancer: epidemiologic
      evidence.
AB  - Energy intake, physical activity, and obesity are modifiable lifestyle factors.
      This chapter reviews and summarizes the epidemiologic evidence on the relation of
      energy intake, physical activity, and obesity to cancer. High energy intake may
      increase the risk of cancers of colon-rectum, prostate (especially advanced
      prostate cancer), and breast. However, because physical activity, body size, and
      metabolic efficiency are highly related to total energy intake and expenditure,
      it is difficult to assess the independent effect of energy intake on cancer risk.
      There are sufficient evidences to support a role of physical activity in
      preventing cancers of the colon and breast, whereas the association is stronger
      in men than in women for colon cancer and in postmenopausal than in premenopausal
      women for breast cancer. The evidence also suggests that physical activity likely
      reduces the risk of cancers of endometrium, lung, and prostate (to a lesser
      extent). On the other hand, there is little or no evidence that the risk of
      rectal cancer is related to physical activity, whereas the results have been
      inconsistent regarding the association between physical activity and the risks of
      cancers of pancreas, ovary and kidney. Epidemiologic studies provide sufficient
      evidence that obesity is a risk factor for both cancer incidence and mortality.
      The evidence supports strong links of obesity with the risk of cancers of the
      colon, rectum, breast (in postmenopausal women), endometrium, kidney (renal
      cell), and adenocarcinoma of the esophagus. Epidemiologic evidence also indicates
      that obesity is probably related to cancers of the pancreas, liver, and
      gallbladder, and aggressive prostate cancer, while it seems that obesity is not
      associated with lung cancer. The role of obesity in other cancer risks is
      unclear.

PMID- 19107435
TI  - Contribution of alcohol and tobacco use in gastrointestinal cancer development.
AB  - Tobacco smoke and alcohol are major risk factors for a variety of cancer sites,
      including those of the gastrointestinal tract. Tobacco smoke contains a great
      number of mutagenic and carcinogenic compounds, including polycyclic
      carbohydrates, nitrosamines, and nicotine, while ethanol per se has only weak
      carcinogenic potential, but its first metabolite, acetaldehyde, is a mutagen and
      carcinogen, since it forms stable adducts with DNA. The possibility of proto
      oncogene mutation in gastrointestinal mucosa cells may be associated with tobacco
      smoking-induced cancers through the formation of unfavorable DNA adducts.
      Individuals with defective DNA repair mechanisms and unfavorable genetic make-up
      for carcinogen metabolism may be at increased risk for gastrointestinal cancers.
      Individuals with a high production rate of acetaldehyde from ethanol also have an
      increased cancer risk when they drink chronically. These include individuals with
      a genetically determined increased acetaldehyde production due to alcohol
      dehydrogenase polymorphism and those with a decreased detoxification of
      acetaldehyde due to acetaldehyde dehydrogenase mutation. In addition, oral
      bacterial overgrowth due to poor oral hygiene also increases salivary
      acetaldehyde. Dietary deficiencies such as a lack of folate, riboflavine, and
      zinc may also contribute to the increase cancer risk in the alcoholic patient. It
      is of considerable importance that smoking and drinking act synergistically.
      Smoking increases the acetaldehyde burden following alcohol consumption and
      drinking enhances the activation of various procarcinogens present in tobacco
      smoke due to increased metabolic activation by an induced cytochrome P450-2E1
      dependent microsomal biotransformation system in the mucosa of the upper
      digestive tract and the liver.

PMID- 19107436
TI  - Role of xenobiotic metabolic enzymes in cancer epidemiology.
AB  - The cause of the majority of cancers is poorly understood albeit multifactorial.
      The ultimate consequence of etiological factors where defined is an alteration
      within the cellular genotype, which is manifested in the cells acquiring
      malignant phenotype. There are several environmental carcinogens that contribute
      to carcinogenesis. These carcinogens are metabolized by a large number of
      enzymes, including the cyto-chrome P 450 group, glutathione-S-transferase (GST),
      the uridine glucuronyl transferase (UGT) super-family, alcohol-metabolizing
      enzymes, sulphatases, etc. These enzymes can either inactivate carcinogens or in
      some cases generate reactive moieties that lead to carcinogenesis. This review
      summarises the available evidence regarding the role of xenobiotic metabolic
      enzymes and their role in cancer epidemiology. The available data and studies
      have identified correlates between expression of various metabolizing enzymes
      with risk of malignancies known to be induced by their substrates. The data may
      have relevance in one population but not for another for a specific malignancy
      and at times may be conflicting. We believe that with mature data in the future
      it may be possible to stratify patients by risk.

PMID- 19107437
TI  - Genetic polymorphisms in the transforming growth factor-beta signaling pathways
      and breast cancer risk and survival.
AB  - The transforming growth factor (TGF)-beta signaling pathway plays a critical role
      in breast cancer development and progression. Limited data from human studies,
      however, are currently available to link biomarkers in this pathway directly to
      the risk and survival of breast cancer. Most of the previous epidemiologic
      studies have focused on evaluating polymorphisms in the TGFB1 gene (T+29C,
      rs1982073) and the TGFBR1 gene (9A/6A), and the results have been inconsistent.
      The present review summarizes epidemiologic evidence regarding the association of
      genetic polymorphisms in the TGF beta pathway genes with breast cancer risk and
      survival and provides rationale and new approaches to continuing the research in
      this area.

PMID- 19107438
TI  - Molecular epidemiology of DNA repair genes in bladder cancer.
AB  - Bladder cancer is a common disease, whose major risk factors include smoking and
      occupational exposure to chemicals. Superficial bladder cancer has significant
      healthcare cost implications due to the need for repeated cystoscopic
      surveillance. Chemical carcinogens can undergo metabolic activation and
      detoxification in the liver and polymorphisms in the relevant genes have been
      shown to be associated with bladder cancer risk. In addition, DNA repair enzymes
      are required to repair the DNA damage associated with carcinogen exposure. The
      main pathways involved are nucleotide excision repair, base excision repair, and
      double strand break repair. Investigation of individual polymorphisms in DNA
      repair genes in bladder cancer has yielded few robust positive findings, which is
      not surprising given the multifactorial nature of the disease. Pathway approaches
      using novel genotyping technologies will allow more comprehensive studies of
      multiple polymorphisms in multiple genes. It will also be possible to investigate
      gene-environment interaction more rigorously than heretofore, using novel
      statistical methodology, in larger studies and through collaborative efforts
      within consortia. The results of the genome-wide association studies in bladder
      cancer are awaited with interest. In the future, genetic tests might be used in
      the prevention of bladder cancer to encourage lifestyle changes in those at
      highest risk of developing the disease, and in the treatment of bladder cancer to
      optimise cure rates whilst minimising morbidity in a cost-effective manner.

PMID- 19107439
TI  - Breast cancer screening and biomarkers.
AB  - Annual screening mammograms have been shown to be cost-effective and are credited
      for the decline in mortality of breast cancer. New technologies including breast
      magnetic resonance imaging (MRI) may further improve early breast cancer
      detection in asymptomatic women. Serum tumor markers such as CA 15-3,
      carcinoembyonic antigen (CEA), and CA 27-29 are ordered in the clinic mainly for
      disease surveillance, and not useful for detection of localized cancer. This
      review will discuss blood-based markers and breast-based markers, such as
      nipple/ductal fluid, with an emphasis on biomarkers for early detection of breast
      cancer. In the future, it is likely that a combination approach to simultaneously
      measure multiple markers would be most successful in detecting early breast
      cancer. Ideally, such a biomarker panel should be able to detect breast cancer in
      asymptomatic patients, even in the setting of normal mammogram and physical
      examination results.

PMID- 19107440
TI  - Epidemiology of brain tumors.
AB  - Gliomas account for more than 70% of all brain tumors, and of these, glioblastoma
      is the most frequent and malignant histologic type (World Health Organization
      [WHO] grade IV). There is a tendency toward a higher incidence of gliomas in
      highly developed, industrialized countries. Some reports indicate that Caucasians
      have a higher incidence than African or Asian populations. With the exception of
      pilocytic astrocytomas (WHO grade I), the prognosis of glioma patients is still
      poor. Fewer than 3% of glioblastoma patients are still alive at 5 years after
      diagnosis, older age being the most significant and consistent prognostic factor
      of poorer outcome. Gliomas are components of several inherited tumor syndromes,
      but the prevalence of these syndromes is very low. Many environmental and
      lifestyle factors including several occupations, environmental carcinogens, and
      diet have been reported to be associated with an elevated glioma risk, but the
      only factor unequivocally associated with an increased risk is therapeutic X
      irradiation. In particular, children treated with X-irradiation for acute
      lymphoblastic leukemia show a significantly elevated risk of developing gliomas
      and primitive neuroectodermal tumors, often within 10 years after therapy.
      Significant correlation between G:C --> A:T transitions in the TP53 gene and
      promoter methylation of the O6 -methylguanine-DNA methyltransferase (MGMT) gene
      in glio-mas have been reported in several studies, suggesting the possible
      involvement of O6-methylguanine DNA adducts, which may be produced by exogenous
      or endogenous alkylating agents in the development of gliomas.

PMID- 19107441
TI  - Mammographic density: a heritable risk factor for breast cancer.
AB  - The appearance of the breast on mammography varies among women, reflecting
      variations in tissue composition. Stroma and epithelium attenuate x-rays more
      than fat and appear light on a mammogram, which we refer to here as "
      mammographic density, " while fat appears dark. We show evidence that
      mammographic density is a strong risk factor for breast cancer, and that risk of
      breast cancer is four to five times greater in women with density in more than
      75% of the breast, compared with those with little or no density. Density in more
      than 50% of the breast may account for a large proportion of breast cancers.
      Density is influenced by age, parity, body mass index, and menopause but these
      factors account for only 20 - 30% of the variation in density in the population.
      Twin studies have shown that percent mammographic density, at a given age, is
      highly heritable, and that inherited factors explain 63% of the variance.
      Mammographic density has the characteristics of a quantitative trait, and may be
      influenced by genes that are easier to identify than those associated with breast
      cancer itself. The genes that influence mammographic density may also be
      associated with risk of breast cancer, and their identification is also likely to
      provide insights into the biology of the breast, and to identify potential
      targets for preventive strategies.

PMID- 19107442
TI  - Acquired risk factors for colorectal cancer.
AB  - The risk of developing colorectal cancer (CRC) is influenced by several acquired
      risk factors, including environmental exposures and comorbid medical conditions
      that are partially genetic in nature. These risk factors are based on data almost
      exclusively derived from observational studies. Because of the possibility of
      bias due to confounding, these acquired risk factors should not be automatically
      assumed to be causative, and in fact some may not be truly independent risk
      factors. Acquired risk factors include the following categories: 1) dietary
      factors, 2) lifestyle factors, 3) side-effects of medical interventions, and 4)
      comorbid medical conditions. Dietary factors that potentially increase the risk
      of CRC include low fruit, vegetable, or fiber intake, high red meat or saturated
      fat consumption, and exposure to caffeine or alcohol. Of these factors, the
      significance of low fruit, vegetable, and fiber intake has been called into
      question because of contradictory results from large observational studies and
      negative results from randomized trials. The association of high red meat or
      saturated fat consumption with increased CRC risk is supported by the
      preponderance of observational data. Lifestyle factors include lack of exercise
      and smoking. These risk factors are supported by observational data of moderate
      quality. Medical interventions that may increase the risk of CRC include pelvic
      irradiation, cholecystectomy, and ureterocolic anastomosis after major surgery of
      the urinary and intestinal tracts. Aside from cholecystectomy, these risk factors
      are supported by observational data from small studies only, therefore their
      validity is not well established. Finally, comorbid medical conditions that are
      associated with increased risk of CRC include Barrett's esophagus, human
      immunodeficiency virus infection, acromegaly, and inflammatory bowel disease. The
      association between inflammatory bowel disease and CRC is well established and it
      forms the basis for widely adopted colonoscopic surveillance recommendations from
      national medical organizations. The other factors are supported by limited
      observational data only and are still controversial.

PMID- 19107443
TI  - Aberrant crypt foci in colon cancer epidemiology.
AB  - Colonic carcinogenesis is characterized by progressive accumulations of genetic
      and epigenetic derangements. These molecular events are accompanied by
      histological changes that progress from mild cryptal architectural abnormalities
      in small adenomas to eventual invasive cancers. The transition steps from normal
      colonic epithelium to small adenomas are little understood. In experimental
      models of colonic carcinogenesis aberrant crypt foci (ACF), collections of
      abnormal appearing colonic crypts, are the earliest detectable abnormality and
      precede adenomas. Whether in fact ACF are precursors of colon cancer, however,
      remains controversial. Recent advances in magnification chromoendoscopy now allow
      these lesions to be identified in vivo and their natural history ascertained.
      While increasing lines of evidence suggest that dysplastic ACF harbor a malignant
      potential, there are few prospective studies to confirm causal relationships and
      supporting epidemiological studies are scarce. It would be very useful, for
      example, to clarify the relationship of ACF incidence to established risks for
      colon cancer, including age, smoking, sedentary lifestyle, and Western diets. In
      experimental animal models, carcinogens dose-dependently increase ACF, whereas
      most chemopreventive agents reduce ACF incidence or growth. In humans, however,
      few agents have been validated to be chemopreventive of colon cancer. It remains
      unproven, therefore, whether human ACF could be used as reliable surrogate
      markers of efficacy of chemopreventive agents. If these lesions could be used as
      reliable biomarkers of colon cancer risk and their reductions as predictors of
      effective chemopreventive agents, metrics to quantify ACF could greatly
      facilitate the study of colonic carcinogenesis and chemoprevention.

PMID- 19107444
TI  - Determinants of incidence of primary fallopian tube carcinoma (PFTC).
AB  - Primary fallopian tube carcinoma (PFTC) is a rare malignancy, but its incidence
      has been rising during the last decades and varies between 2.9/1,000,000 and
      5.7/1,000,000. The epidemiology of PFTC has been sparsely studied. In Finland,
      the incidence rate has been rising during the last decades. The rise has been
      highest in the cities, in higher social classes, and in certain specific
      occupations. Parity gives protection against this disease, as does a previous
      sterilization procedure. Earlier thoughts of a previous salpingitis as a possible
      promoter of PFTC seem not to hold. Previous infections such as Chlamydia
      trachomatis infections or human papillomavirus infections cannot be regarded as
      risk factors. In this chapter, we clarify the possible epidemiological factors
      behind this disease.

PMID- 19107445
TI  - The changing epidemiology of lung cancer.
AB  - The 20th century witnessed the scourge of lung cancer as the disease rapidly rose
      the ranks to become the commonest cause of cancer mortality in the world.
      Epidemiological evidence conclusively associated cigarette smoking with the
      causation of lung cancer in the 1950s. Since then and the few decades after, lung
      cancer of the squamous cell or small cell histological subtypes was mainly
      diagnosed among male smokers in developed countries. As we move into the 21st
      century, the incidence of lung cancer is unlikely to abate but the burden will
      shift from the developed to the less-developed countries. Other epi-demiological
      changes of lung cancer include the narrowing of the gap between men and women
      affected by the disease, predominance of the adenocarcinoma histological subtypes
      as well as more never-smokers afflicted with the disease. Unless we eliminate
      tobacco smoking completely, lung cancer will continue its wrath into the 21st
      century.

PMID- 19107446
TI  - Epidemiology of ovarian cancer.
AB  - Ovarian cancer represents the sixth most commonly diagnosed cancer among women in
      the world, and causes more deaths per year than any other cancer of the female
      reproductive system. Despite the high incidence and mortality rates, the etiology
      of this disease is poorly understood. Established risk factors for ovarian cancer
      include age and having a family history of the disease, while protective factors
      include increasing parity, oral contraceptive use, and oophorectomy. Lactation,
      incomplete pregnancies, and surgeries such as hysterectomy and tubal ligation may
      confer a weak protective effect against ovarian cancer. Infertility may
      contribute to ovarian cancer risk among nulliparous women. Other possible risk
      factors for ovarian cancer include postmenopausal hormone-replacement therapy and
      lifestyle factors such as cigarette smoking and alcohol consumption. Many of the
      causes of ovarian cancer are yet to be identified. Additional research is needed
      to better understand the etiology of this deadly disease.

PMID- 19107447
TI  - Epidemiology, pathology, and genetics of prostate cancer among African Americans
      compared with other ethnicities.
AB  - Prostate cancer is the most common cancer affecting men in the Western world. In
      the United States, it is the second leading cause of cancer related deaths after
      lung and bronchus carcinoma. No definitive causes of prostate cancer (PCa) have
      been identified to date but, increasing age, a positive family history, and sub
      Saharan African ancestry are strongly linked to its development. African American
      men (AAM) have the highest reported incidence rates in the United States and
      their mortality from the disease is markedly higher than that of European
      American men (EAM). Conversely, Asian American men and Pacific Islanders (API),
      American Indian and Alaskan Native (AI/AN) men, and Hispanic men all have lower
      incidence and mortality rates as compared with EAM. The reasons for these
      differences are unclear. However, it is clear that AAM have more advanced PCa
      when diagnosed. Several other reasons have been suggested and these include
      differences in treatments and health seeking behavior among the ethnic groups,
      cultural beliefs, environmental/lifestyle factors, dietary and genetic factors.
      In conclusion, there are multiple factors that impact prostate cancer outcome and
      that may be responsible for ethnic disparity. These factors are discussed in this
      chapter.

PMID- 19107448
TI  - Racial differences in clinical outcome after prostate cancer treatment.
AB  - Prostate cancer is the number one killer in the United States. A comparison of US
      and Japanese population is discussed in this chapter to identify risk factors for
      prostate cancer. Screening of prostate cancer is common among Americans, but not
      among Japanese. A comparison of survival in different populations is also
      presented; and prognosis after hormonal treatment in different populations is
      included.

PMID- 19107449
TI  - Epidemiology of stomach cancer.
AB  - Despite a major decline in incidence and mortality over several decades, stomach
      cancer is still the fourth most common cancer and the second most common cause of
      cancer death in the world. There is a 10-fold variation in incidence between
      populations at the highest and lowest risk. The incidence is particularly high in
      East Asia, Eastern Europe, and parts of Central and South America, and it is
      about twice as high among men than among women. Prognosis is generally rather
      poor, with 5-year relative survival below 30% in most countries. The best
      established risk factors for stomach cancer are Helicobacter pylori infection,
      the by far strongest established risk factor for distal stomach cancer, and male
      sex, a family history of stomach cancer, and smoking. While some factors related
      to diet and food preservation, such as high intake of salt-preserved foods and
      dietary nitrite or low intake of fruit and vegetables, are likely to increase the
      risk of stomach cancer, the quantitative impact of many dietary factors remains
      uncertain, partly due to limitations of exposure assessment and control for
      confounding factors. Future epidemiologic research should pay particular
      attention to differentiation of stomach cancer epidemiology by subsite, and to
      exploration of potential interactions between H. pylori infection, genetic, and
      environmental factors.

PMID- 19107450
TI  - [Use of diclofenac for tonsillectomy].

PMID- 19107451
TI  - [Pharyngeal hemorrhaging due to iatrogenic false aneurysm. Complication after
      cannulation of the internal jugular vein].
AB  - Catheterization of the internal jugular vein is used for temporary access to the
      central vein in patients with acute or chronic renal failure. The most frequent
      problem is the arterial puncture and accidental placement of the large catheter
      in an artery. This case report describes a rare secondary complication by
      accidental catheterization of the right common carotid artery after intended dual
      lumen catheter insertion into the right internal jugular vein. A false aneurysm
      with pharyngeal hemorrhaging developed 2 weeks after the puncture. The diagnosis
      was made using colour-Doppler ultrasound and the aneurysm was treated with
      vascular surgery.

PMID- 19107452
TI  - [Postpartum cerebral venous sinus thrombosis after epidural anaesthesia].
AB  - Cerebral venous sinus thrombosis during pregnancy or puerperium is not a rarity.
      Nevertheless, it is often misdiagnosed. With the increasing use of regional
      anaesthesia in obstetrics the differential diagnosis of postdural puncture
      headache is often difficult. The case of a patient is reported who suffered from
      both intracranial hypotension and cerebral venous sinus thrombosis in the
      postpartum period.

PMID- 19107453
TI  - The mammal assemblage of the hominid site TM266 (Late Miocene, Chad Basin):
      ecological structure and paleoenvironmental implications.
AB  - Characterizing the paleoenvironmental context of the first hominids is a key
      issue for understanding their behavioral and morphological evolution. The present
      study aims at reconstructing the paleoenvironment of the TM266 vertebrate
      assemblage (Toros-Menalla, Northern Chad) that yielded the earliest known hominid
      Sahelanthropus tchadensis (7 Ma). For the first time, a quantitative analysis is
      carried out on the fossil mammal assemblage associated with that hominid. Two
      complementary approaches were applied: (1) the analysis of the relative
      abundances of taxa and their habitat preferences; and (2) the study of the
      distribution of taxa within three meaningful ecovariables: locomotion, feeding
      preferences, and body mass. The resulting taxonomic and paleoecological
      structures are used to reconstruct the diversity and the relative extent of the
      habitats in that part of northern Chad seven million years ago. The
      paleoenvironment was composed of open areas with dry and humid grasslands,
      prevailing over wooded habitats. Water was also widely available as freshwater
      bodies and certainly swamps. It appears that the high habitat diversity of the
      landscape is a common feature among paleoenvironments associated with early
      hominids.

PMID- 19107454
TI  - Host pollination mode and mutualist pollinator presence: net effect of internally
      ovipositing parasite in the fig-wasp mutualism.
AB  - The Ficus-their specific pollinating fig wasps (Chalcidoidea, Agaonidae)
      interaction presents a striking example of mutualism. Figs also shelter numerous
      non-pollinating fig wasps (NPFW) that exploit the fig-pollinator mutualism. Only
      a few NPFW species can enter figs to oviposit, they do not belong to the
      pollinating lineage Agaonidae. The internally ovipositing non-agaonid fig wasps
      can efficiently pollinate the Ficus species that were passively pollinated.
      However, there is no study to focus on the net effect of these internally
      ovipositing non-agaonid wasps in actively pollinated Ficus species. By collecting
      the data of fig wasp community and conducting controlled experiments, our results
      showed that internally ovipositing Diaziella bizarrea cannot effectively
      pollinate Ficus glaberrima, an actively pollinated monoecious fig tree.
      Furthermore, D. bizarrea failed to reproduce if they were introduced into figs
      without Eupristina sp., the regular pollinator, as all the figs aborted.
      Furthermore, although D. bizarrea had no effect on seed production in shared
      figs, it significantly reduced the number of Eupristina sp. progeny emerging from
      them. Thus, our experimental evidence shows that reproduction in Diaziella
      depends on the presence of agaonid pollinators, and whether internally
      ovipositing parasites can act as pollinators depends on the host fig's
      pollination mode (active or passive). Overall, this study and others suggest a
      relatively limited mutualistic role for internally ovipositing fig wasps from non
      pollinator (non-Agaonidae) lineages.

PMID- 19107455
TI  - Homing in the wolf spider Lycosa tarantula (Araneae, Lycosidae): the role of
      active locomotion and visual landmarks.
AB  - Previous studies on the homing of the wolf spider Lycosa tarantula have shown
      that it is carried out by path integration. Animals using this mechanism must
      measure the distance walked and the angles turned. This study aims to understand
      if wolf spider L. tarantula is able to estimate the walked distance in an outward
      path. As this information is more likely obtained by proprioceptive mechanisms,
      active or passive displacements have been performed. An active locomotion was
      found essential to estimate distances. During passive locomotion, spiders
      searched for their burrows near the release point while when displaced actively
      the inbound journey was longer than the outbound one. The possible use of visual
      landmarks near the burrow was also tested as a cue to complete the inbound
      journey. Our results did not show that L. tarantula used these visual landmarks
      to find the burrow. L. tarantula seems to use only proprioceptive information
      obtained during the outbound path to estimate the distance traveled.

PMID- 19107457
TI  - [MRI for malignant pancreatic tumors].
AB  - In recent years continuous advancements in software and hardware technology of
      modern MRI systems have contributed to substantial progress in the field of
      pancreatic tumor imaging. Despite technical advances in abdominal MRI, multislice
      CT still remains the preferential diagnostic tool for pancreatic lesions. In the
      majority of cases the essential clinical questions can thereby be answered with a
      high degree of accuracy. However, in dilemma cases state-of-the-art MR imaging
      can provide relevant information for the diagnosis allowing an optimal
      therapeutic concept. This report gives an overview on possible applications for
      MRI in the diagnostic evaluation of malignant pancreatic tumors.

PMID- 19107458
TI  - Important differences: Canadian Diabetes Association 2008 clinical practice
      guidelines and the consensus statement of the American Diabetes Association and
      the European Association for the Study of Diabetes.

PMID- 19107456
TI  - The evolutionary continuum of limb function from early theropods to birds.
AB  - The bipedal stance and gait of theropod dinosaurs evolved gradually along the
      lineage leading to birds and at some point(s), flight evolved. How and when did
      these changes occur? We review the evidence from neontology and paleontology,
      including pectoral and pelvic limb functional morphology, fossil
      footprints/trackways and biomechanical models and simulations. We emphasise that
      many false dichotomies or categories have been applied to theropod form and
      function, and sometimes, these impede research progress. For example,
      dichotomisation of locomotor function into 'non-avian' and 'avian' modes is only
      a conceptual crutch; the evidence supports a continuous transition.
      Simplification of pelvic limb function into cursorial/non-cursorial morphologies
      or flexed/columnar poses has outlived its utility. For the pectoral limbs, even
      the classic predatory strike vs. flight wing-stroke distinction and separation of
      theropods into non-flying and flying--or terrestrial and arboreal--categories may
      be missing important subtleties. Distinguishing locomotor function between taxa,
      even with quantitative approaches, will always be fraught with ambiguity, making
      it difficult to find real differences if that ambiguity is properly acknowledged.
      There must be an 'interpretive asymptote' for reconstructing dinosaur limb
      function that available methods and evidence cannot overcome. We may be close to
      that limit, but how far can it be stretched with improved methods and evidence,
      if at all? The way forward is a combination of techniques that emphasises
      integration of neontological and paleontological evidence and quantitative
      assessment of limb function cautiously applied with validated techniques and
      sensitivity analysis of unknown variables.

PMID- 19107459
TI  - [Multidirectional shoulder instability. Nonoperative and operative treatment
      strategies].
AB  - Multidirectional shoulder instability (MDI) is characterized by symptomatic
      instability in at least two directions, often with a global hyperlaxity. The
      etiology is mostly atraumatic, with an acquired or congenital enlarged capsular
      volume or redundancy. Muscular imbalances and pathologic patterns of muscle
      recruitment and motion are also common findings. Traumatic onset of MDI is rare,
      although capsulolabral lesions can be found during surgery. Therapy aims at a
      normalization of muscle balance/weakness and motion patterns. If conservative
      treatment fails, arthroscopic capsular plication techniques, in combination with
      repair of labral and interval lesions, can accomplish results similar to those of
      classic open techniques but with reduced morbidity and invasiveness.

PMID- 19107460
TI  - [Pathomorphology of shoulder instability].
AB  - In cases of a traumatic anterior first-time dislocation of the shoulder,
      pathomorphological changes may initially occur at three different sites: at the
      capsule itself, at its origin or at its insertion. The typical injury is an
      avulsion of the labrum and the capsule from the glenoid and is called a Bankart
      lesion. There is a tendency to underestimate the amount of plastic deformation of
      the capsule and alternative injuries, such as avulsion of the capsule from the
      humeral head (HAGL lesion). Bony deformities at the humeral head or at the
      glenoid are of utmost importance for the prognosis of shoulder instability. In
      the dislocated position the anterior glenoid rim may notch the posterior surface
      of the humeral head (Hill-Sachs lesion). Bony defects of the glenoid may be
      caused by a fracture or due to chronic wear (fracture or erosion type). If bony
      defects exceed a certain size, isolated reconstruction of soft tissues does not
      guarantee stability of the shoulder.

PMID- 19107462
TI  - Resuscitation with hyperoncotic colloids in the intensive care unit.

PMID- 19107463
TI  - Multiple ligament knee reconstruction clinical follow-up and gait analysis.
AB  - Multiple ligament knee injuries are serious and rare injures that have not been
      studied using advanced gait analysis techniques. The purpose of this study was to
      perform clinical follow-up and gait analysis on patients with multiple knee
      ligament reconstruction. Twenty-four patients who underwent a multi-ligament knee
      reconstruction by a single surgeon volunteered to participate in this study. We
      performed complete clinical exam including instrumented ACL exam (KT-1000), and
      radiological exam including weight-bearing and PCL stress radiographs (TELOS) at
      minimum 2 years post index surgery. In addition, we performed complete three
      dimensional gait analysis on 18 patients. We used a 10-camera, high speed (120
      Hz) motion analysis system in conjunction with a multi-axis strain-gage force
      plate which calculated knee joint kinetics and kinematics while subjects
      performed flat-ground walking and stair-descent tasks. Kinematic and kinetic
      variables were compared between reconstructed and contralateral knees and
      unmatched, healthy control knees. All knee joint moments were normalized to
      subjects' weight. Clinical: Average knee joint flexion/extension 123.6 +/-
      15.5/1.7 +/- 3.5, respectively. Average KT-1000 side-to-side difference was 1.2
      +/- 2.0 mm, TELOS side-to-side difference on stress radiographs was 4.0 +/- 3.1
      mm. Median IKDC score was 67 (range 13-94). Fifty-three percent of patients
      exhibited radiographic evidence of osteoarthritis (OA) on the operative side; one
      patient on the contralateral knee. During gait analysis, patients exhibited
      significantly reduced total knee joint range of motion, and external knee flexion
      moment in the reconstructed knee compared to the contralateral knee and healthy
      control knees. The magnitude of these differences was greater while descending a
      step. Finally, patients who had radiographic evidence of knee joint OA had
      significantly lower magnitude external knee flexion moment compared to those who
      did not have OA at the time of follow-up. Greater than 2 years after
      reconstruction, patients with multi-ligament knee injuries are able to return to
      daily activities. Gait analysis data suggests that patients may be experiencing
      higher magnitude changes in sagittal plane kinematics and kinetics during
      demanding functional tasks (stair decent). Changes in walking gait biomechanics
      may help explain why this group is experiencing unilateral knee joint
      degeneration.

PMID- 19107464
TI  - A plea for rigorous and honest science: false positive findings and biased
      presentations in epidemiological studies.

PMID- 19107466
TI  - WAY-163909, a 5-HT2C agonist, enhances the preclinical potency of current
      antipsychotics.
AB  - INTRODUCTION: 5-HT(2C) agonists, by decreasing mesolimbic dopamine without
      affecting nigrostriatal dopamine, are predicted to have antipsychotic efficacy
      with low extrapyramidal side effects (EPS). Combining 5-HT(2C) agonists with low
      doses of existing antipsychotics could increase treatment efficacy while reducing
      treatment liabilities such as EPS (typical antipsychotics), and the propensity
      for weight gain (atypical antipsychotics). OBJECTIVES: The objectives of these
      studies were to combine WAY-163909, a selective 5-HT(2C) agonist, with either the
      typical antipsychotic haloperidol, or the atypical antipsychotic clozapine, at
      doses that were ineffective on their own, with the expectation that a shift in
      potency in several rodent behavior models predictive of antipsychotic activity
      would occur. RESULTS AND DISCUSSION: In mice, co-administration of either
      haloperidol, or clozapine, produced a significant leftward shift in the ability
      of WAY-163909 to block apomorphine-induced climbing behavior, without any affect
      on apomorphine-induced stereotypy or an increased propensity for catalepsy. In
      the rat-conditioned avoidance model, WAY-163909 was combined with either
      haloperidol or clozapine at doses that individually produced reductions in
      avoidance response on the order of 10%, while the combination of WAY-163909 and
      either of the antipsychotics resulted in a greater than 70% reduction in
      avoidance, with no evidence of response failures, or pharmacokinetic interaction.
      CONCLUSION: Doses of either haloperidol or clozapine, that failed to antagonize
      an MK-801 induced deficit in prepulse inhibition, significantly attenuated the
      sensory gating deficit when combined with WAY-163909. Data support the notion
      that 5-HT(2C) receptor agonists, co-administered with other marketed
      antipsychotics, allow for dose sparing with a more favorable side-effect profile.

PMID- 19107465
TI  - 24-h smoking abstinence potentiates fMRI-BOLD activation to smoking cues in
      cerebral cortex and dorsal striatum.
AB  - RATIONALE: Exposure to smoking-related cues can trigger relapse in smokers
      attempting to maintain abstinence. OBJECTIVES: In the present study, we evaluated
      the effect of 24-h smoking abstinence on brain responses to smoking-related cues
      using functional magnetic resonance imaging (fMRI). MATERIALS AND METHODS:
      Eighteen adult smokers underwent fMRI scanning following smoking as usual
      (satiated condition) and following 24-h abstinence (abstinent condition). During
      scanning, they viewed blocks of photographic smoking and control cues. RESULTS:
      Following abstinence, greater activation was found in response to smoking cues
      compared to control cues in parietal (BA 7/31), frontal (BA 8/9), occipital (BA
      19), and central (BA 4) cortical regions and in dorsal striatum (putamen) and
      thalamus. In contrast, no smoking cue greater than control cue activations were
      observed following smoking as usual. Direct comparisons between conditions
      (satiated vs. abstinent) showed greater brain reactivity in response to smoking
      cues following abstinence. In addition, positive correlations between pre-scan
      craving in the abstinent condition and smoking cue activation were observed in
      right dorsomedial prefrontal cortex (dmPFC) including superior frontal gyrus (BA
      6/10), anterior cingulate gyrus (BA 32), and supplementary motor area (BA 6).
      CONCLUSIONS: The present findings indicate that smoking abstinence significantly
      potentiates neural responses to smoking-related cues in brain regions subserving
      visual sensory processing, attention, and action planning. Moreover, greater
      abstinence-induced craving was significantly correlated with increased smoking
      cue activation in dmPFC areas involved in action planning and decision making.
      These findings suggest that drug abstinence can increase the salience of
      conditioned cues, which is consistent with incentive-motivation models of
      addiction.

PMID- 19107467
TI  - Microarray of DNA-protein complexes on poly-3-hydroxybutyrate surface for
      pathogen detection.
AB  - A novel strategy was developed for the specific immobilization of DNA probes on
      poly-3-hydroxybutyrate (PHB) surface by using the substrate-binding domain (SBD)
      of PHB depolymerase as an active binding motif. To demonstrate whether this
      method can be used for the detection of clinical pathogens, the pathogen-specific
      biotin-labeled DNA probes were immobilized via core streptavidin (cSA) fused to
      the SBD. The pathogen-specific 15-mer oligonucleotide probes were designed for
      four model pathogens, while the target DNAs were prepared by PCR using universal
      primers. The complex of pathogen-specific probes and cSA-SBD fusion protein was
      immobilized on the PHB-coated slide by microspotting. This DNA-protein complex
      microarray was able to successfully diagnose Acinetobacter baumannii, Escherichia
      coli, Klebsiella pneumoniae, and Pseudomonas aeruginosa. Furthermore, the
      specific pathogens could be diagnosed in the presence of other microorganisms.
      Thus, the DNA-protein complex microarray platform technology employing PHB and
      the SBD reported here can be widely used for the detection of DNA-DNA and DNA
      biomolecule interactions without synthetic or chemical modification of
      biomolecules or solid surface.

PMID- 19107468
TI  - Separation of Cinchona alkaloids on a novel strong cation-exchange-type chiral
      stationary phase-comparison with commercially available strong cation exchanger
      and reversed-phase packing materials.
AB  - A recently reported chiral strong cation exchanger (cSCX) type stationary phase
      was investigated for the LC separation of a series of Cinchona alkaloids and
      synthetic derivatives thereof to test its usefulness as alternative methodology
      for the separation of those important pharmaceuticals. The cSCX column-packing
      material was qualitatively compared on the one hand against a commercially
      available non-enantioselective SCX-material, PolySulfoethyl-A, and, on the other
      hand, against a modern C18 reversed-phase stationary phase which is commonly
      employed for Cinchona alkaloid analysis. Both SCX columns showed no pronounced
      peak-tailing phenomena which typically hamper Cinchona alkaloid RP analysis and
      require specific optimization. Thus, the cSCX-based assay provided new
      feasibilities for the separation of the Cinchona alkaloids in polar organic mode
      as opposed to conventional reversed-phase methodologies. In particular, a method
      for the simultaneous determination of eight Cinchona alkaloids (quinine,
      quinidine, cinchonine, cinchonidine, and their corresponding dihydro analogs)
      using the cSCX column in HPLC has been developed and exemplarily applied to
      impurity profiling of a commercial alkaloid sample. Furthermore, both SCX
      materials allowed successful separation of C9-epi and 10,11-didehydro derivatives
      from their respective educts in an application in synthetic Cinchona alkaloid
      chemistry.

PMID- 19107469
TI  - Persistence of antimuscarinic drug use.
AB  - PURPOSE: Evidence suggests antimuscarinic drugs for the overactive-bladder
      syndrome only confer modest improvements in quality of life. We wanted to
      describe the persistence of therapy, including an extended analysis beyond the 1
      year follow-up employed in other studies. METHODS: All prescriptions for drugs in
      ATC category G04BD were retrieved for the period 1999-2006 from a regional
      database with complete capture of all reimbursed prescriptions. Kaplan-Meyer
      curves were generated for duration of treatment for each substance and analyzed
      for determinants of termination. RESULTS: With the exception of trospium
      chloride, all drugs had continuation rates of less than 50% at 6 months, less
      than 25% at 1 year, and less than 10% at 2 years and longer. Trospium chloride,
      however, exhibited continuation rates of 46% at 6 months, 36% at 1 year, 22% at 2
      years, and 16% at 3 years. CONCLUSIONS: In a setting of socialized medicine, we
      found higher continuation rates than previously published. Interestingly, we
      found that one of the older drugs on the market, trospium chloride, had a
      strikingly longer retention rate than other drugs.

PMID- 19107470
TI  - Effect of anaerobic promoters on the microaerobic production of
      polyhydroxybutyrate (PHB) in recombinant Escherichia coli.
AB  - Nine anaerobic promoters were cloned and constructed upstream of PHB synthesis
      genes phbCAB from Ralstonia eutropha for the micro- or anaerobic PHB production
      in recombinant Escherichia coli. Among the promoters, the one for alcohol
      dehydrogenase (PadhE) was found most effective. Recombinant E. coli JM 109
      (pWCY09) harboring PadhE and phbCAB achieved a 48% PHB accumulation in the cell
      dry weight after 48 h of static culture compared with only 30% PHB production
      under its native promoter. Sixty-seven percent PHB was produced in the dry weight
      (CDW) of an acetate pathway deleted (Deltapta deletion) E. coli JW2294 harboring
      the vector pWCY09. In a batch process conducted in a 5.5-l NBS fermentor
      containing 3 l glucose LB medium, E. coli JW2294 (pWCY09) grew to 7.8 g/l CDW
      containing 64% PHB after 24 h of microaerobic incubation. In addition, molecular
      weight of PHB was observed to be much higher under microaerobic culture
      conditions. The high activity of PadhE appeared to be the reason for improved
      micro- or anaerobic cell growth and PHB production while high molecular weight
      contributed to the static culture condition.

PMID- 19107471
TI  - Construction of quintuple protease gene disruptant for heterologous protein
      production in Aspergillus oryzae.
AB  - Aspergillus oryzae has received attention as a host for heterologous protein
      production. However, A. oryzae has 134 protease genes, which is recognized to be
      one of the major reasons for the proteolytic degradation of heterologously
      produced proteins. We previously reported that double disruption of the protease
      genes (tppA and pepE) improved heterologous protein (human lysozyme) production
      by A. oryzae. In this study, we performed successive round of five protease genes
      (tppA, pepE, nptB, dppIV, and dppV) disruption in A. oryzae by pyrG marker
      recycling with highly efficient gene-targeting background (DeltaligD). The
      multiple disruption of protease genes were confirmed by Southern blot analysis.
      Furthermore, the quintuple protease gene disruptants showed the maximum
      production level of bovine chymosin (CHY) that was 34% higher than those of the
      double protease gene disruptant (DeltatppA DeltapepE). Consequently, we
      successfully constructed a multiple protease gene disruptant bearing enhanced
      levels of CHY productivity. We presented the first evidence that the quintuple
      disruption of the protease genes improved the production level of a heterologous
      protein by A. oryzae.

PMID- 19107472
TI  - Use of allylthiourea to produce soluble methane monooxygenase in the presence of
      copper.
AB  - Methanotrophs expressing soluble methane monooxygenase (sMMO) may find use in a
      variety of industrial applications. However, sMMO expression is strongly
      inhibited by copper, and the growth rate may be limited by the aqueous solubility
      of methane. In this study, addition of allylthiourea decreased intracellular
      copper in Methylosinus trichosporium OB3b, allowing sMMO production at Cu/biomass
      ratios normally not permitting sMMO synthesis. The presence of about 1.5
      micromoles intracellular Cu g(-1) dry biomass resulted in sMMO activity of about
      250 micromoles 1-napthol formed per hour gram dry biomass whether this
      intracellular Cu concentration was achieved by Cu limitation or by allylthiourea
      addition. No loss of sMMO activity occurred when the growth substrate was
      switched from methane to methanol when allylthiourea had been added to growth
      medium containing copper. Addition of copper to medium that was almost copper
      free increased the yield of dry biomass from methanol from 0.20 to 0.36 g g(-1),
      demonstrating that some copper was necessary for good growth. This study
      demonstrated a method by which sMMO can be produced by M. trichosporium OB3b
      while growing on methanol in copper-containing medium.

PMID- 19107473
TI  - Short chain regioselectively hydrolyzed scleroglucans induce maturation of
      porcine dendritic cells.
AB  - Branched beta-1,3/1,6-glucans (scleroglucan) were produced by cultivation of
      Sclerotium rolfsii ATCC 15205. Regioselective hydrolysis at the beta-1,3-linkage
      of the cell-free and purified polysaccharide was performed in borosilicate glass
      bottles at pH 5, 121 degrees C, and 1 bar for 72 h. The mixture was divided into
      four molar mass fractions by stepwise cross-flow filtration using different
      cutoffs. In vitro studies revealed that scleroglucan hydrolysates with a low
      molar mass of less than 5 kDa significantly stimulated the activation and
      maturation of porcine monocyte derived dendritic cells (MoDC) by upregulation of
      CD40 and CD80/86 as well as by reduction of antigen uptake. MoDC treated with low
      molar mass scleroglucan showed a considerable increase in the amounts of secreted
      proinflammatory cytokine tumor necrosis factor alpha and stimulated the
      proliferation of lymphocytes. Therefore, scleroglucan molecules of low molecular
      weight are able to induce activation and maturation of porcine DC, which are key
      initiators of inflammatory and adaptive immune responses, and could provide
      improved protection against infectious diseases.

PMID- 19107474
TI  - Versatile capacity of shuffled cytochrome P450s for dye production.
AB  - DNA family shuffling is a relatively new method of directed evolution used to
      create novel enzymes in order to improve their existing properties or to develop
      new features. This method of evolution in vitro has one basic requirement: a high
      similarity of initial parental sequences. Cytochrome P450 enzymes are relatively
      well conserved in their amino acid sequences. Members of the same family can have
      more than 40% of sequence identity at the protein level and are therefore good
      candidates for DNA family shuffling. These xenobiotic-metabolising enzymes have
      an ability to metabolise a wide range of chemicals and produce a variety of
      products including blue pigments such as indigo. By applying the specifically
      designed DNA family shuffling approach, catalytic properties of cytochrome P450
      enzymes were further extended in the chimeric progeny to include a new range of
      blue colour formations. This mini-review evokes the possibility of exploiting
      directed evolution of cytochrome P450s and the novel enzymes created by DNA
      family shuffling for the production of new dyes.

PMID- 19107475
TI  - A xylanase with high pH stability from Streptomyces sp. S27 and its carbohydrate
      binding module with/without linker-region-truncated versions.
AB  - A xylanase gene, xynAS27, was isolated from a genomic library of Streptomyces sp.
      S27. The full-length gene consists of 1,434 bp and encodes 477 amino acids,
      including a putative signal peptide of 41 residues at its N-terminus. The mature
      xylanase comprises two functional domains, a family 10 glycoside hydrolase, and a
      family 13 carbohydrate-binding module (CBM), which were joined by a short Gly/Pro
      rich linker region. The intact, the CBM-truncated and the CBM-linker-truncated
      versions of the mature proteins were expressed in Escherichia coli BL21 (DE3),
      purified to electrophoretic homogeneity and subsequently characterized. XynAS27
      showed high pH stability over the pH range 2.2-12.0. XynAS27 may be a compelling
      tool for the food industry because it generates xylobiose (85% w/w) as the main
      product of xylan hydrolysis. The truncated versions showed less pH and thermal
      stability, and less affinity and hydrolytic activity to insoluble substrate than
      the intact one. These results indicate that the CBM of XynAS27 plays a key role
      in the hydrolysis of insoluble substrate, and the CBM and linker region are also
      important for the enzyme stability, and the linker region contributes more.

PMID- 19107476
TI  - Novel detector technology for clinical PET.
AB  - INTRODUCTION: Positron emission tomography (PET) is the most sensitive of all
      medical imaging modalities for quantitatively probing biologic processes at the
      molecular level. However, spatial resolution in PET is significantly inferior to
      that of other imaging modalities that can provide exquisite images of the
      anatomy, such as X-ray computed tomography (CT) or magnetic resonance (MR)
      imaging. OBJECTIVE: It has been one of the outstanding challenges of the last
      decade to combine PET with these complementary imaging modalities in order to
      synergistically exploit the benefits of each modality and to enhance the role of
      PET in pre-clinical research as well as in clinical routine and research.
      DISCUSSION: The simple juxtaposition of tomographs around a common axial bed,
      such as with current PET/CT technology, is very successful in allowing sequential
      acquisition of PET and anatomical data. However, novel imaging combinations are
      being considered that would enable simultaneous, or at least concurrent, dual
      modality imaging through combined PET/MR or PET/CT. The development of these new
      integrated instruments creates new bewildering challenges for PET detection
      systems, which, in addition to the ability to measure annihilation radiation in
      PET, must satisfy several other critical requirements.

PMID- 19107477
TI  - Induction of iodide uptake in transformed thyrocytes: a compound screening in
      cell lines.
AB  - PURPOSE: Retinoic acid presently is the most advanced agent able to improve the
      efficacy of radioiodine therapy in differentiated thyroid carcinoma. In order to
      identify compounds with higher efficacy a panel of pharmacologically well
      characterized compounds with antitumour action in solid cancer cell lines was
      screened. METHODS: The effects of the compounds on iodide uptake, cell number,
      proliferation and apoptosis were evaluated. RESULTS: In general, compounds were
      more effective in cell lines derived from more aggressive tumours. The
      effectiveness in terms of number of responsive cell lines and maximal increase in
      iodide uptake achieved decreased in the order: APHA > valproic acid approximately
      sirolimus approximately arsenic trioxide > retinoic acid approximately lovastatin
      > apicidine approximately azacytidine approximately retinol approximately
      rosiglitazone approximately bortezomib. CONCLUSION: We hypothesize that testing
      of cells from primary tumours or metastases in patients may be a way to identify
      compounds with optimum therapeutic efficacy for individualized treatment.

PMID- 19107479
TI  - Image of the month. FDG-PET in paraneoplastic limbic encephalitis.

PMID- 19107480
TI  - Diagnostics of "non-acute" vascular prosthesis infection using 18F-FDG PET/CT:
      our experience with 96 prostheses.
AB  - INTRODUCTION: Vascular prosthesis infection (VPI) is a life-threatening
      complication that occurs in 0.5-5% of prostheses. Low-grade infections in non
      acute patients are a diagnostic challenge requiring a new method with good
      diagnostic accuracy. The aim of this work was to define the accuracy of (18)F-FDG
      PET/CT in these settings and to identify essential parameters of the evaluation.
      MATERIAL AND METHODS: PET/CT was performed prospectively in 76 consecutive
      patients with a total of 96 vascular prosthetic grafts in which infection was
      suspected. PET/CT scans were analysed in terms of the presence and intensity of
      focal and diffuse FDG uptake, the presence of an anastomotic pseudoaneurysm, the
      presence of an irregular boundary of infiltration, a combination of these, and
      the uptake ratio between the graft and blood background. The gold standard was
      based on operative/histopathological finding or a clinical follow up of >6
      months. RESULTS: Among the various assessed parameters only focal FDG uptake and
      an irregular graft boundary were significant predictors of VPI. Focal intense FDG
      uptake together with an irregular boundary of the lesion on CT scan predicted VPI
      with 97% probability, while smooth lesion boundaries and no focal FDG uptake
      predicted a probability of VPI of less than 5%. Even in lesions with
      nondiagnostic inhomogeneous focal FDG uptake (18/96) an irregular boundary
      effectively helped in decision-making with a probability of 28% (smooth) or 77%
      (irregular) for VPI. CONCLUSION: PET/CT gave reliable results with an accuracy
      >95% in 75% of prostheses. PET/CT can identify those prostheses (25% of
      prosthesis) for which its diagnostic accuracy is diminished to 70-75%. In our
      series PET/CT was an excellent diagnostic modality for suspected VPI.

PMID- 19107481
TI  - Does regular blood transfusion prevent progression of cerebrovascular lesions in
      children with sickle cell disease?
AB  - A retrospective study was conducted to assess changes in cerebrovascular lesions,
      as assessed by magnetic resonance (MR) imaging and angiography in 18 children
      with sickle cell disease (SCD) receiving optimised chronic transfusions for
      primary stroke prevention (abnormal transcranial Doppler flow, nine patients,
      median follow-up 14.3 months (range, 7.9-48.9)) or secondary stroke prevention
      (nine patients, median follow-up 59.6 months (range, 11.0-127.9)). An experienced
      neuroradiologist blinded to patient data reviewed the 41 MR scans
      (median/patient, three (2-4)). Standard scores were used to evaluate parenchymal
      and vascular abnormalities at baseline and last follow-up. Within-patient score
      changes evaluated using Wilcoxon's paired rank test indicated lesion progression
      in the secondary-prevention group (p = 0.027). Optimised transfusion therapy does
      not prevent progression of cerebral vasculopathy in SCD children with a history
      of stroke.

PMID- 19107482
TI  - L-asparaginase in the treatment of refractory and relapsed extranodal NK/T-cell
      lymphoma, nasal type.
AB  - There is no standard salvage regimen for patients with refractory and relapsed
      extranodal NK/T-cell lymphoma (NKTCL), nasal type. This study was conduced to
      evaluate the efficacy of L-asparaginase-based regimen as a salvage regimen, on
      refractory and relapsed extranodal NKTCL, nasal type. Between March 1996 and
      March 2008, 45 patients with refractory and relapsed extranodal NKTCL, nasal
      type, were studied retrospectively. All patients were treated with L-asparaginase
      based salvage regimen. Thirty-nine patients also received primary involved-field
      radiation after L-asparaginase-based chemotherapy. The complete response rate,
      partial response rate, and overall response rate for the whole group were 55.6%,
      26.7%, and 82.2%, respectively. Both of 3-year and 5-year overall survival (OS)
      rates were 66.9%. The major adverse effects of L-asparaginase were
      myelosuppression, liver dysfunction, hyperglycemia, and allergic reaction. In
      general, the side effects could be tolerated. On univariate analysis, age, the
      stage of disease, and performance status were found to be prognostic factors
      influencing OS. On multivariate analysis, the stage of disease and age were
      independent prognostic factors for OS. L-Asparaginase-based regimen was obviously
      effective for the patients with refractory and relapsed extranodal NKTCL, nasal
      type.

PMID- 19107483
TI  - Cardiac involvement in sickle beta-thalassemia.
AB  - Cardiovascular involvement is a leading cause of mortality and morbidity in
      patients with inherited hemoglobinopathies, but it has not been adequately
      assessed in sickle beta-thalassemia. We evaluated 115 sickle beta-thalassemia
      patients, aged 34 +/- 14 years, along with 50 healthy controls, by resting
      echocardiography. Patients with systolic left ventricular (LV) dysfunction or
      severe pulmonary hypertension (PHT) also underwent left and right cardiac
      catheterization and cardiac magnetic resonance imaging (CMR). Left and right
      chamber dimensions, LV mass, and cardiac index were significantly higher in
      patients compared to controls (p < 0.001 in most cases). Three patients (2.9%)
      had reduced LV ejection fraction (<55%); mean LV ejection fraction was
      significantly lower in patients (p < 0.001). Left and right ventricular systolic
      tissue Doppler indices and LV diastolic tissue Doppler indices were also impaired
      in patients. All three patients with systolic LV dysfunction had normal coronary
      arteries and mild myocardial iron load (CMR T2* values, 18-25 ms). Systolic
      pulmonary artery pressure was significantly higher in patients compared to
      controls (p = 0.002); PHT was present in 28 patients (27%), while severe PHT in
      three (2.9%). In three patients with severe PHT, only one had impaired LV
      ejection fraction and increased pulmonary wedge pressure. Overall, three patients
      (2.9%) had a history of heart failure, two with systolic LV dysfunction, and one
      with severe PHT. Cardiac involvement in sickle beta-thalassemia concerns
      biventricular dilatation and dysfunction along with PHT, leading to congestive
      heart failure.

PMID- 19107484
TI  - A complex 1;19;11 translocation involving the MLL gene in a patient with
      congenital acute monoblastic leukemia identified by molecular and cytogenetic
      techniques.

PMID- 19107485
TI  - Early severe toxicities after capecitabine intake: possible implication of a
      cytidine deaminase extensive metabolizer profile.
AB  - We report here the case of a 19-year-old female patient who suffered from
      extremely severe toxicities (G4 mucitis, fever, diarrhea, alteration of general
      state) while undergoing low-dose capecitabine treatment for her metastatic
      corticosurrenaloma. The severe toxicities stopped as soon as treatment was
      suspended. Interestingly, this patient was not deficient in DPD, a
      pharmacogenetic syndrome usually associated with increased risk of developing
      severe/lethal toxicities in patients undergoing fluoropyrimidine therapy, and she
      had been treated previously with 5-FU with a good tolerance. We then hypothesized
      that cytidine deaminase (CDA) extensive phenotype could be responsible for the
      severe toxicities observed with capecitabine. CDA is affected by genetic
      polymorphism, with subsequent acquisition of either deficient or extensive
      metabolizer profile. Phenotypic investigations confirmed that CDA activity in
      this patient was +180% higher than the ones usually recorded in the general
      population. This strongly suggests that the extensive activation of triple
      prodrug capecitabine could have occurred in this patient, resulting in
      overexposure to 5-FU and its cytotoxic metabolites eventually. This case report
      suggest for the first time that severe toxicities with a capecitabine-containing
      protocol could be, at least in part, linked with an extensive-CDA syndrome. The
      case reported here suggests therefore that besides DPD, screening for CDA
      activity could be of interest to ensure a better safety in the handling of oral
      capecitabine at the bedside.

PMID- 19107487
TI  - Automated measurement of lymph nodes: a phantom study.
AB  - The purpose of this study was to assess the accuracy of automated nodal
      quantification in a phantom. MDCT of a phantom with 17 synthetic lymph nodes of
      different sizes (diameter 6.0-30.0 mm) was performed at varying tube currents,
      reconstruction kernels and slice thicknesses. RECIST diameter and volume were
      measured using an automated software tool. Results were compared with the
      reference diameter and volume by calculating the absolute percentage error (APE).
      Degree of agreement between software and reference measurements was evaluated by
      computing corresponding concordance correlation coefficients (CCC). Under varying
      tube currents the mean APE (CCC) varied between 5.18% and 10.12% (0.95-0.99) for
      RECIST diameter and between 7.22% and 16.21% (0.94-1.00) for the volume. At
      different reconstruction kernels the mean APE values ranged between 7.20% and
      7.55% (0.99) (RECIST) and between 8.96% and 14.42% (1.00) (volume). With
      different slice thicknesses the mean APE values differed from 5.81% to 9.20%
      (0.97-0.99) (RECIST) and from 8.16% to 22.66% (0.99-1.00) (volume). Regarding
      RECIST criteria and volume, automated evaluation of lymph nodes in a phantom
      demonstrated a high accuracy under varying MDCT parameters.

PMID- 19107486
TI  - The green algal eyespot apparatus: a primordial visual system and more?
AB  - Most flagellate green algae exhibiting phototaxis posses a singular specialized
      light sensitive organelle, the eyespot apparatus (EA). Its design principles are
      similar in all green algae and produce, in conjunction with the movement pattern
      of the cell, a highly directional optical device. It enables an oriented movement
      response with respect to the direction and intensity of light. The functional EA
      involves local specializations of different compartments (plasma membrane,
      cytosol, and chloroplast) and utilizes specialized microbial-type rhodopsins,
      which act as directly light-gated ion channels. Due to their elaborate structures
      and the presence of retinal-based photoreceptors in some lineages, algal EAs are
      thought to play an important role in the evolution of photoreception and are thus
      not only of interest to plant biologists. In green algae considerable progress in
      the molecular dissection of components of this primordial visual system has been
      made by genetic and proteomic approaches in recent years. This review summarizes
      general aspects of the green algal EA as well as recent progress in the
      identification of proteins related to it. Further, novel data supporting a link
      between eyespot globules and plastoglobules will be presented and potential
      additional roles of the EA besides those in photoreception will be discussed.

PMID- 19107488
TI  - Maintenance of biological rhythms during hibernation in Eastern woodchucks
      (Marmota monax).
AB  - We undertook a study to determine presence of circadian rhythms during woodchuck
      hibernation using continuously monitored body temperatures. Males had shorter
      torpor and longer euthermic periods than females. Circular statistics revealed a
      significant mean vector for males entering into torpor (10:21 h), but not for
      females. No significant mean vector was found for male or female arousal from
      torpor. A contingency test was applied to the torpor bout durations. All 7 males
      tested had significant tau's between 24 and 26 h, while 6 of the 13 females
      tested had significant tau's with a range of 22-27 h. These results implicate a
      free-running circadian clock during torpor bouts. Overall, the data support the
      existence of biological rhythms during hibernation in woodchucks, especially for
      males during arousals. Since entries into torpor appear to be synchronized for
      males, arousal periods may be used to resynchronize their circadian system. The
      persistence of biological rhythms during hibernation may help to insure
      successful mating in the spring after emergence.

PMID- 19107489
TI  - MRI to demonstrate diagnostic features and complications of TBM not seen with CT.
AB  - BACKGROUND: Computed tomography (CT) findings in children with tuberculous
      meningitis (TBM) often do not explain the clinical presentation and may even be
      normal. Magnetic resonance imaging (MRI) has the potential to diagnose TBM with
      greater sensitivity than CT and also to detect more infarcts. AIM: The aim of
      this study was to determine whether MRI demonstrates features and complications
      of TBM not present on CT. MATERIALS AND METHODS: Retrospective, blinded
      evaluation and comparison of CT and MRI findings in children with TBM were
      performed. RESULTS: Of 30 children included, MRI demonstrated eight more with
      basal enhancement and four more with infarctions. Overall, MRI demonstrated an
      additional 104 sites of infarction (of a total 172) than CT. Of these, 89 were
      acute and visualized only on diffusion-weighted image. MRI showed five more
      patients with unilateral and two more with bilateral basal ganglia infarcts than
      CT as well as 19 brainstem infarcts. Hydrocephalus was equally detected by MRI
      and CT. CONCLUSION: MRI is superior to CT for diagnosing TBM (by detecting basal
      enhancement in more patients) and prognosis (by detecting many more infarcts in
      strategic locations). The role of CT is defined for the acute setting in
      detecting hydrocephalus for surgical management.

PMID- 19107490
TI  - Efficacy of temozolomide for recurrent embryonal brain tumors in children.
AB  - OBJECTIVE: The salvage therapy of recurrent embryonal brain tumors in children is
      disappointing. Temozolomide is a newly developed chemotherapeutic agent in
      central nervous system tumors. This study analyzed the efficacy of temozolomide
      on the treatment of recurrent embryonal brain tumors in children. MATERIALS AND
      METHODS: There were eight patients, including four with medulloblastoma (MB),
      three with atypical teratoid/rhabdoid tumor (AT/RT) and one with supratentorial
      primitive neuroectodermal tumor, whose tumors recurred after surgery and
      radiotherapy, with or without conventional intravenous cisplatin-based
      chemotherapy. They all received once daily oral temozolomide (150 mg/m(2)/day)
      for five consecutive days in a 28-day cycle. The responsiveness of the tumors to
      temozolomide was judged by magnetic resonance imaging (MRI) during regular follow
      up. RESULTS: The median treatment cycles received by these eight patients were 17
      (range from two to 59 cycles). The follow-up MRI showed no tumor progression in
      five patients at 6 months and four patients at 12 months. The median progression
      free survival (PFS) of the eight patients was 15.7 months (range from 0 to 59
      months). Complete response was achieved in one patient with MB accompanying with
      a long period of PFS for 26 months. Another patient with AT/RT showed partial
      response accompanying with a long period of PFS for 59 months. The observed
      adverse effects of temozolomide included nausea, vomiting, headache,
      constipation, mild marrow suppression, and decreased activity; none of them was
      severe enough to discontinue the treatment. No patient experienced moderate or
      severe marrow suppression in this series. CONCLUSION: In this preliminary study,
      oral temozolomide shows promising results on recurrent embryonal brain tumors in
      children. The adverse effects of temozolomide are mild and tolerable. When
      conventional chemotherapy fails and/or the adverse response is too severe to
      tolerate, temozolomide is a reasonable alternative. However, a further well
      designed, controlled study and more long-term follow-up are needed to assess the
      exact role of temozolomide in children with embryonal tumors in brain.

PMID- 19107491
TI  - Prenatal diagnosed cyst of the quadrigeminal cistern in Aicardi syndrome.
AB  - Aicardi syndrome is an X-linked dominant disorder characterized by the
      pathognonomic association of three clinical signs: agenesis of the corpus
      callosum, infantile spasms, and chorioretinal lacunae. This is a severe syndrome
      with an estimated survival rate of 76% at 6 years and 40% at 14 years and a
      maximum developmental level like a 12-month-old baby in 91% of cases. We
      illustrate a case of Aicardi syndrome with bilateral, small chorioretinal
      lacunae, infantile spasms with a typical hypsarrhythmia, defects of thoracic
      vertebra and bilateral absence of the 12th rib associated with an arachnoid cyst
      of the quadrigeminal cistern, and presence of the corpus callosum with a
      favorable outcome.

PMID- 19107492
TI  - Hydrogen peroxide at a concentration used during neurosurgery disrupts ciliary
      function and causes extensive damage to the ciliated ependyma of the brain.
AB  - OBJECTIVES: Hydrogen peroxide [H(2)O(2): 3% w/v (1.1 M)] has been used as a
      haemostatic agent during neurosurgery applied to both the external and
      ventricular surface of the brain. We hypothesised that H(2)O(2) would be toxic to
      the ciliated ependyma, a single layer of cells that separates cerebrospinal fluid
      from the neuronal tissue of the brain. MATERIALS AND METHODS: The effect of
      H(2)O(2) was assessed by determining ependymal ciliary beat frequency (CBF) using
      high-speed video analysis and ultrastructure by electron microscopy. RESULTS:
      Brief exposure to H(2)O(2) caused cessation of ciliary beat frequency and
      extensive damage of the ependyma. CONCLUSIONS: Damage to the ciliated ependyma is
      of concern, as regeneration following damage is very poor and if breached
      underlying neuronal tissue and a population of neuronal progenitor cells that lie
      immediately beneath may also be exposed to H(2)O(2).

PMID- 19107493
TI  - Minicraniotomy for endoscopic third ventriculostomy in babies: technical note
      with a 7-year-segment analysis.
AB  - INTRODUCTION: An alternative approach to the burr hole technique for endoscopic
      third ventriculostomy (ETV) in babes, the minicraniotomy, is described. It is
      easily performed and allows to close the dura mater and restore the bone
      integrity. Since 2002, it is the approach to ETV in babes with open fontanel in
      our service. RESULTS: Analyzing 41 surgeries, the technique did not interfere
      with the safety and efficacy of the procedure. No cerebrospinal fluid leak
      occurred. The minicraniotomy seems to be appropriate and advantageous to that
      age.

PMID- 19107494
TI  - Neuroinvasion of the 263K scrapie strain after intranasal administration occurs
      through olfactory-unrelated pathways.
AB  - The olfactory system has been implicated in the pathogenesis of transmissible
      spongiform encephalopathies (TSEs). To examine this issue and identify the
      pattern of TSE agent spread after intranasal administration, we inoculated a high
      infectious dose of neurotropic scrapie strain 263K into the nasal cavity of
      Syrian hamsters. All animals allowed to survive became symptomatic with a mean
      incubation period of 162.4 days. Analysis at different time points revealed
      deposition of the pathological prion protein (PrP(TSE)) in nasal-associated
      lymphoid tissues in the absence of brain involvement from 80 days post-infection
      (50% of the incubation period). Olfactory-related structures and brainstem nuclei
      were involved from 100 days post-inoculation (62% of the incubation period) when
      animals were still asymptomatic. Intriguingly, vagal or trigeminal nuclei were
      identified as early sites of PrP(TSE) deposition in some pre-symptomatic animals.
      These findings indicate that the 263K scrapie agent is unable to effectively
      spread from the olfactory neuroepithelium to the olfactory-related structures and
      that, after intranasal inoculation, neuroinvasion occurs through olfactory
      unrelated pathways.

PMID- 19107495
TI  - The role of physiotherapy in the treatment of whiplash associated disorders: a
      prospective study.
AB  - OBJECTIVES: Prospective longitudinal study to evaluate the effect of
      physiotherapy on whiplash associated disorders (WAD). MATERIALS AND METHODS: A
      total of 141 patients suffering from grades I-III WAD after a road traffic
      accident were employed. Validated neck Bournemouth Questionnaire was used in
      order to look at the effect of treatment on the symptoms. RESULTS: The mean age
      was 40 (+/-14) years. The mean length of the treatment was 6 (+/-3.4) weeks. The
      mean individual effect size was 0.97 (95% CI 0.8-1.2). A total of 67% of the
      patients who started their treatment in the first 3 months post-injury improved
      compared to 48% in those who started physiotherapy after 3 months (P = 0.025). In
      both groups the applied treatment almost halved the number of patients taken sick
      leave. CONCLUSION: Physiotherapy is effective in the treatment of whiplash
      injury, especially in order to get the patients fit to go back to their previous
      employment.

PMID- 19107496
TI  - Closing lateral wedge valgus osteotomy with dynamic hip screw for the treatment
      of varus nonunion of pertrochanteric fracture: can restoration of biomechanics
      and stabilization alone heal?
AB  - INTRODUCTION: Nonunion of pertrochanteric fracture is rare and its occurrence
      especially without prior surgical intervention has been hardly ever reported.
      Hence there is not much literature describing the best way to treat them.
      Nonunion of pertrochanteric fracture collapses in to varus by virtue of deforming
      action of muscles and thus deranging the biomechanics of the hip and indirectly
      preventing fracture union further. Hence it is very important to re-orient the
      abductor lever arm to biomechanically advantageous normal configuration favoring
      fracture healing. In general, principles of treatment of nonunion like open
      reduction of the fracture with freshening of fracture fragments, stabilization
      and bone grafting are very difficult to the surgeon and the patient. METHOD: We
      herewith describe for the first time in literature a prospective nonrandomized
      study of closing lateral wedge valgus intertrochanteric osteotomy in addition to
      dynamic hip screw osteosynthesis in the successful management of seven patients
      with varus trochanteric nonunion. Average operating time was 63 +/- 13 min (range
      39-93 min) and blood loss was 212 +/- 32 ml (range 156-320 ml). Average pre
      operative coxa vara of 94 degrees +/- 7 degrees (range 85 degrees -104 degrees )
      had improved to a femoral neck shaft angle of 139 degrees +/- 4 degrees (range
      134 degrees -145 degrees ) on postoperative radiographs. RESULTS: All fractures
      and osteotomies had healed uneventfully at the last follow-up with good
      functional outcome. Harris Hip score had improved from 34 +/- 6 (range 22-47) to
      89 +/- 4 (range 83-95) at an average of 11 months (range 7-13 months) follow-up.
      Valgus osteotomy converts shear forces across the fracture site into compressive
      forces thus achieving union.

PMID- 19107497
TI  - Successful management of interstitial pregnancy with fetal cardiac activity by
      laparoscopic-assisted cornual resection with preoperative transcatheter uterine
      artery embolization.
AB  - INTRODUCTION: Interstitial pregnancy is a rare but dangerous form of ectopic
      pregnancy. Although various forms of minimally invasive management for this
      disorder have been previously reported, optimal treatment regimen has not been
      yet unknown due to its rarity. CASE REPORT: A 29-year-old married woman with no
      previous disease history was referred under suspicion of ectopic pregnancy. Serum
      hCG value was 95,365 mIU/mL. On ultrasonographic examination, gestational sac
      with a viable embryo was identified in the left cornual region. Three-dimensional
      computed tomographic angiography showed prominent vascular mass in the left
      cornual region. Preoperative transcatheter uterine artery embolization followed
      by laparoscopic-assisted cornual resection with local methotrexate injection was
      successfully performed. CONCLUSIONS: Laparoscopic-assisted cornual resection with
      preoperative transcatheter uterine artery embolization for interstitial pregnancy
      with prominent vascular flow is a safe and reliable minimally invasive procedure
      for woman wishing fertility preservation.

PMID- 19107498
TI  - An extraordinary cause of vertebral fracture in pregnant woman: brucellosis.
AB  - Herein, we report the unique case of Brucella-related lumbar vertebral fracture
      in a first trimester pregnant woman. The unique effective treatment protocol for
      the infection is prolonged combined antibiotics and immobilization with follow
      up, even in the presence of vertebral fracture related to spinal disease. With
      the accurate choice of anthiobitics (suitable, non-teratogenic and non-toxic for
      the fetus) therapeutic abortion is not indicated.

PMID- 19107499
TI  - Inhibin A levels and severity of preeclampsia.
AB  - OBJECTIVE: To evaluate the use of third trimester inhibin A levels to assess the
      severity of preeclampsia. MATERIALS AND METHODS: Blood samples were taken from
      women diagnosed with mild and severe preeclampsia during the third trimester of
      pregnancy. Blood samples were collected in plain tubes, centrifuged and stored at
      -80 degrees C until analyzed. All serum samples were measured for inhibin A
      levels by enzyme-linked immunosorbent assays. RESULTS: Inhibin A levels were
      greater in the severe (1,435.9 +/- 603.2 pg/mL) than in the mild preeclampsia
      group (1,021.9 +/- 438.8 pg/mL, P = 0.014). CONCLUSION: Inhibin A levels rise
      with increasing severity of disease. However, there is considerable overlap of
      serum inhibin A levels in women with mild and severe preeclampsia. Inhibin A is
      therefore not a useful adjunct for the classification of preeclampsia.

PMID- 19107500
TI  - High mean platelet volume, low-grade systemic coagulation and fibrinolytic
      activation are associated with androgen and insulin levels in polycystic ovary
      syndrome.
AB  - OBJECTIVES: The present study was designed to determine (a) the coagulation
      parameters, WBC and MPV levels; (b) whether there was any association between
      androgen and mean platelet volume and low-grade systemic coagulation in PCOS
      patients. METHODS: A total of 48 patients with non-diabetic PCOS were studied in
      order to evaluate and compare with a non-PCOS group of 30 subjects. RESULTS: D
      dimer, homeostatic model assessment (HOMA-IR), insulin, androgens, glucose, WBC
      and MPV concentrations were higher in women with PCOS. No difference was observed
      in fibrinogen, activated partial thromboplastin time and prothrombin time values
      between the two groups. Free testosterone was positively correlated with D-dimer,
      insulin, DHEAS, and MPV levels. In multiple stepwise regression analyses, free
      testosterone positively associated with D-dimer and DHEAS. MPV was positively
      correlated with insulin levels, HOMA-IR values, DHEAS and free testosterone
      levels in PCOS patients. In multiple stepwise regression analyses, MPV positively
      associated with insulin and DHEAS. CONCLUSION: PCOS patients had low-grade
      systemic coagulation and fibrinolytic activation as evidenced by elevated D
      dimer, and increased WBC and MPV levels suggesting that hematological parameters
      could potentially be used as indicators of risk factor for atherosclerosis in
      PCOS women.

PMID- 19107501
TI  - Burkitt's lymphoma related to Epstein-Barr virus infection during pregnancy.
AB  - SETTING: Burkitt's lymphoma is a rare form of cancer and is an extremely rare
      diagnosis during pregnancy. This form of lymphoma is a very fast growing B cell
      neoplasm and chemotherapy is the treatment of choice for the disease in all its
      stages. CASE REPORT: The authors describe the case of a Caucasian 40-year-old
      nulliparous woman, with previous known Epstein-Barr virus infection, that
      presents at 28 weeks gestation with supraclavicular adenopathy and multiple
      bilateral breast nodules, in which biopsy showed non-Hodgkin lymphoma, Burkitt's
      type. DISCUSSION: There are few described cases of Burkitt's lymphoma during
      pregnancy and in general the outcomes have been poor. In most of the cases, the
      patients were not treated by current standards or instead had a late diagnosis.
      This neoplasia is the most rapidly progressive human tumor, and any delay in
      initiating therapy can adversely affect patient's prognosis. The authors discuss
      treatment options in pregnancy and its perinatal implications.

PMID- 19107502
TI  - Peeling of internal limiting membrane during vitrectomy for complicated retinal
      detachment prevents epimacular membrane formation.
AB  - BACKGROUND: To investigate the clinical benefit of internal limiting membrane
      (ILM) peeling at the macula for the prevention of epimacular membrane formation
      following vitreous surgery using silicone oil for the treatment of complicated
      retinal detachment. METHODS: This was a non-randomized, retrospective,
      interventional study of a case series. Patient charts were reviewed
      retrospectively for 20 consecutively recruited patients who underwent successful
      primary vitrectomy with ILM peeling at the macula using silicone oil (group 1)
      and 22 consecutively recruited patients who underwent successful primary
      vitrectomy using silicone oil without ILM peeling at the macula for complicated
      rhegmatogenous retinal detachment (group 2). The main outcome measures were
      distant visual acuity and epimacular membrane formation. The data were analyzed
      and compared using Fisher's Exact test, Pearson Chi-square test, independent t
      test, Mann-Whitney U-test, and a repeated ANOVA. RESULTS: The mean age of
      patients was 52.7 +/- 12.6 years in group 1 and 53.2 +/- 13.3 years in group 2 (p
      = 0.89). The mean follow-up time was 24.6 +/- 7.6 weeks in group 1 and 34.1 +/-
      12.6 weeks in group 2 (p = 0.01). Preoperatively, ten eyes in group 1 and 10 eyes
      in group 2 were pseudophakic; the macula was detached in all cases. Silicone oil
      had been removed from all eyes of both groups at least 3 months before the final
      examination. There were no significant differences between the two groups with
      regard to sex (p = 0.44), mean duration of retinal detachment (p = 0.12), mean
      preoperative visual acuity (logMAR), mean number of retinal breaks (p = 0.43),
      and grade of proliferative vitreoretinopathy (p = 0.35). The final visual acuity
      (logMAR) was 0.60 +/- 0.30 in group 1 and 0.72 +/- 0.35 in group 2 (p = 0.49).
      Four eyes in group 1 and two eyes in group 2 underwent cataract surgery during
      silicone oil removal. Epimacular membrane formation was observed in two eyes
      before silicone oil removal and in four eyes within 8 weeks after silicone oil
      removal in group 2. No epimacular membrane formation was seen in group 1 (p =
      0.02). CONCLUSION: ILM peeling at the macula during vitreous surgery with
      silicone oil for the treatment of complicated retinal detachment may prevent
      epimacular membrane formation without negatively affecting distant visual acuity.

PMID- 19107503
TI  - Efficacy of probing for children with congenital nasolacrimal duct obstruction: a
      retrospective study using fluorescein dye disappearance test and lacrimal sac
      echography.
AB  - PURPOSE: To evaluate B-scan echography for the assessment of lacrimal sac (LS) in
      pediatric epiphora secondary to congenital nasolacrimal duct obstruction (CNLDO),
      and to verify its predictive role in functional efficacy of nasolacrimal duct
      probing. PATIENTS AND METHODS: Thirty-nine eyes of 23 consecutive children,
      treated with a single probing for persistent CNLDO-related epiphora, were
      retrospectively studied. These cases were investigated both collectively and
      considering two sub-groups: group A (ten patients [20 eyes] <or=13 months) and
      group B (13 patients [19 eyes] >13 months. Fluorescein dye disappearance test at
      10 minutes (FDDT-10) and ultrasound examination of LS were performed before and
      after probing. An echographic LS scoring system (grade 0 = no LS enlargement;
      grade 1 = slight longitudinal LS enlargement; grade 2 = longitudinal and slight
      transverse LS enlargement; grade 3 = marked longitudinal and transverse LS
      enlargement) was introduced as a predictor of probing efficacy, estimating FDDT
      10 modification between pre- and post-operative checks. RESULTS: Echographic LS
      evaluation was easily practicable without sedation. In the total cluster and in
      both age sub-groups, post-probing FDDT-10 decreased with respect to pre-probing
      value (p < 0.001). Post-probing LS score improved with respect to pre-probing
      check within the total cluster and group A (p < 0.05). Strong correlation between
      pre-probing LS alteration and functional probing failure was present in each
      studied cluster (all p values <0.0001). Within group B, a greater gain of post
      probing FDDT-10 was more frequent in patients with a better pre-probing LS score,
      as well as in younger children (both p values <0.0001). CONCLUSIONS: In children
      with CNLDO-related epiphora, B-scan echography of the LS can represent a reliable
      and useful examination for a better understanding of the functional prognosis
      after probing treatment.

PMID- 19107504
TI  - Differential expression of the integrins alpha6Abeta4 and alpha6Bbeta4 along the
      crypt-villus axis in the human small intestine.
AB  - The integrin alpha6 subunit exists as two different variants, termed alpha6A and
      alpha6B. These two variants have been shown to harbor potentially distinct
      biochemical properties but little is known about their cellular function. The aim
      of this work was to characterize the expression of the integrin alpha6A and B
      variants in relation to cell proliferation and differentiation in the human small
      intestinal epithelium. The results showed distinct expression patterns for the
      two variants along the crypt-villus axis. Indeed, proliferative cells of the
      crypt were found to predominantly express alpha6A, while differentiated
      enterocytes and Paneth cells expressed the alpha6B variant. A similar
      relationship was observed in intestinal cell models by competitive RT-PCR.
      Further studies in the Caco-2 cell model showed that manipulating the cellular
      balance of the two alpha6 variants can influence transcriptional activities
      related to cell proliferation but not differentiation. This suggests that
      differential expression of the alpha6 subunits is involved in the intestinal
      epithelial cell renewal process. Further studies will be needed to substantiate
      this hypothesis.

PMID- 19107505
TI  - Effect of high intensity intermittent training on heart rate variability in
      prepubescent children.
AB  - The purpose of this study was to observe the effect of high intermittent exercise
      training on children's heart rate variability (HRV). Thirty-eight children (age
      9.6 +/- 1.2 years) were divided into an intermittent (IT, n = 22) and a control
      group (CON, n = 16). At baseline and after a 7-week training period, HRV
      parameters, peak oxygen consumption (VO(2peak)) and maximal aerobic velocity
      (MAV) were assessed. Training consisted of three 30-min sessions composed by
      short maximal and supramaximal runs at velocities ranging from 100 up to 190% of
      MAV. HRV was computed in time and frequency domains. Training resulted in a
      significant increase in MAV and VO(2peak) in IT (P < 0.05) only without any
      significant change in HRV parameters for the two groups. Thus, 7 weeks of high
      intermittent exercise training allows to improve aerobic fitness. However, this
      modality of training was not sufficient enough to underline a possible effect on
      the heart rate autonomic regulation in children.

PMID- 19107506
TI  - Energy based devices and recurrent laryngeal nerve injury: the need for safer
      instruments.

PMID- 19107510
TI  - Ovary-drip transformation: a simple method for directly generating vector- and
      marker-free transgenic maize (Zea mays L.) with a linear GFP cassette
      transformation.
AB  - The presence of selectable marker genes and vector backbone sequences has
      affected the safe assessment of transgenic plants. In this study, the ovary-drip
      method for directly generating vector- and selectable marker-free transgenic
      plants was described, by which maize was transformed with a linear GFP cassette
      (Ubi-GFP-nos). The key features of this method center on the complete removal of
      the styles and the subsequent application of a DNA solution directly to the
      ovaries. The movement of the exogenous DNA was monitored using fluorescein
      isothiocyanate-labeled DNA, which showed that the time taken by the exogenous DNA
      to enter the ovaries was shortened compared to that of the pollen-tube pathway.
      This led to an improved transformation frequency of 3.38% compared to 0.86% for
      the pollen-tube pathway as determined by PCR analysis. The use of 0.05%
      surfactant Silwet L-77 + 5% sucrose as a transformation solution further
      increased the transformation frequency to 6.47%. Southern blot analysis showed
      that the transgenic plants had low transgene copy number and simple integration
      pattern. Green fluorescence was observed in roots and immature embryos of
      transgenic plants by fluorescence microscopy. Progeny analysis showed that GFP
      insertions were inherited in T(1) generation. The ovary-drip method would become
      a favorable choice for directly generating vector- and marker-free transgenic
      maize expressing functional genes of agronomic interest.

PMID- 19107511
TI  - Conflicts as signals: bridging the gap between conflict detection and cognitive
      control.

PMID- 19107512
TI  - Actions travel with their objects: evidence for dynamic event files.
AB  - Moving a visual object is known to lead to an update of its cognitive
      representation. Given that object representations have also been shown to include
      codes describing the actions they were accompanied by, we investigated whether
      these action codes "move" along with their object. We replicated earlier findings
      that repeating stimulus and action features enhances performance if other
      features are repeated, but attenuates performance if they alternate. However,
      moving the objects in which the stimuli appeared in between two stimulus
      presentations had a strong impact on the feature bindings that involved location.
      Taken together, our findings provide evidence that changing the location of an
      object leaves two memory traces, one referring to its original location (an
      episodic record) and another referring to the new location (a working-memory
      trace).

PMID- 19107513
TI  - Object-based selection operating on a spatial representation made salient by
      dimensional segmentation mechanisms: a re-investigation of Egly and Homa (1984).
AB  - Three experiments re-investigated selective attention in the 'ring-cueing'
      paradigm of Egly and Homa (J Exp Psychol: Human Percept Perform 10:778-793,
      1984). Observers were cued to attend to one of three concentric rings of radius 1
      degrees, 2 degrees, or 3 degrees, and their signal detection accuracy for cued
      and uncued rings was measured. Experiment 1, which used a central color cue to
      indicate a like-colored ring, replicated ring-cueing effects along the lines of
      Egly and Homa. Experiments 2 and 3 examined whether these effects were produced
      by observers exploiting secondary-depth cues possibly inherent in the display
      layout. With color cues, the availability of secondary-depth information had no
      influence on the ring-cueing effects. However, making the rings monochrome and
      using central size cues significantly reduced the ring-cueing effects when the
      depth information was disrupted. The results suggest that selection was object
      based, operating on a spatial 'grouped-array' representation of the cued ring
      made salient by color- or depth-based segmentation mechanisms.

PMID- 19107515
TI  - Pachyonychia congenita type 2, N92S mutation of keratin 17 gene: clinical
      features, mutation analysis and pathological view.
AB  - Pachyonychia congenita (PC) type 2 is a rare inherited genetic disease
      characterized by hypertrophic nail dystrophy, palmoplantar hyperkeratosis and
      multiple pilosebaceous cysts. In some cases, natal teeth and hair abnormalities
      may be present. It is caused by mutations in keratin 17 or its expression partner
      keratin 6b. Here, an N92S (p.Asn92Ser) germline keratin 17 gene mutation in a
      pachyonychia congenita type 2 female patient is presented. The pedigree includes
      the 15 members of a family who showed a severe expression of the phenotype for
      six generations with a similar clinical picture consisting of sebaceous cysts,
      nail dystrophy, hyperkeratosis, hair abnormalities, natal teeth, hoarseness and
      hyperhydrosis. In conclusion, we emphasize the importance of diagnosing and
      managing pachyonychia congenita in childhood for the assistance of affected
      children and for the development of potential therapies.

PMID- 19107514
TI  - Vascular lesions of bone in children, adolescents, and young adults. A
      clinicopathologic reappraisal and application of the ISSVA classification.
AB  - Vascular lesions of bone are rare and their terminology is not standardized.
      Herein, we report 77 patients with such lesions in order to characterize their
      morphologic spectrum and the applicability of the International Society for the
      Study of Vascular Anomalies (ISSVA) classification. In this system, malformations
      are structural anomalies distinguishable from tumors, which are proliferative.
      The radiologic images/reports and pathologic materials from all patients were
      reviewed. All lesions were either restricted to bone or had minimal contiguous
      soft tissue involvement with the exception of some multifocal lymphatic lesions
      that extensively affected soft tissue and/or viscera. We found that certain
      lesions of bone often regarded as tumors should be classified as malformations.
      Malformations (n = 46) were more common than tumors (n = 31); lymphatic and
      venous malformations were equally frequent. In the tumor category,
      hemangioendothelioma and epithelioid hemangioma were the most common. We also
      describe new vascular entities that arise in or involve bone. Utilizing the ISSVA
      approach, the diverse and often contradictory terminology of vascular lesions of
      bone can be largely eliminated. Standardized nomenclature is critical for
      scientific communication and patient management, and we hereby recommend the
      ISSVA classification be applied to vascular lesions of bone, just as for skin,
      soft tissue, and viscera.

PMID- 19107516
TI  - Prognosis of pentalogy of Cantrell depends mainly on the severity of the
      intracardiac anomalies and associated malformations.
AB  - We believe the paper may be of particular interest to the readers of your
      journal. It is a commentary on van Hoorn et al: Pentalogy of Cantrell: two
      patients and a review to determine prognostic factors for optimal approach (Eur J
      Pediatr (2008) 167:29-35). The correct definition of pentalogy of Cantrell and
      ectopia cordis was described in the text and the determinant factor that affects
      the prognosis of pentalogy of Cantrell was discussed.

PMID- 19107517
TI  - Is serum procalcitonin a reliable diagnostic marker in children with acute
      respiratory tract infections? A retrospective analysis.
AB  - INTRODUCTION: Acute respiratory tract infections (ARI) in children are often
      treated with antibiotics even without evidence of bacterial infection. Serum
      procalcitonin (PCT) is elevated in bacterial but not in viral infections.
      PATIENTS AND METHODS: We performed a retrospective analysis of children in the
      PID-ARI.net study on respiratory infections to address the question of whether
      plasma PCT could potentially distinguish between bacterial infections requiring
      antibiotic therapy and viral ARI. We analysed data on 327 children who had been
      included in the German PID-ARI.net study and in whom nasopharyngeal aspirates had
      been analysed with a 19-valent multiplex reverse transcription-polymerase chain
      reaction-enzyme-linked immunosorbent assay for viral and atypical bacterial
      pathogens. Serum PCT was determined using a quantitative immunoassay (BRAHMS
      Kryptor PCTsensitive, Henningsdorf, Germany). We then focussed specifically on
      those children who were treated with antibiotics and therefore had been suspected
      of having bacterial infection but who had a serum PCT level lower than 0.1 ng/ml.
      RESULTS: Out of 327 children, 132 had serum PCT levels below 0.1 ng/ml. Of these
      132, 38 children had been treated with antibiotics. After exclusion of 26
      patients (with critical illnesses, antibiotics on admission or for reasons other
      than ARI), 12 children remained for further evaluation. Of these 12 children,
      four had atypical pneumonia; four others had positive virus testing, and, in the
      last four, the aetiology of ARI remained unknown; evidence of bacterial infection
      could not be detected in any. CONCLUSIONS: Taken the results of this
      retrospective analysis, serum PCT values below 0.1 ng/ml might be a marker to
      identify children with acute respiratory tract infection in whom antibiotic
      treatment could be withheld. However, only a prospective intervention trial will
      prove the general safety of this limit.

PMID- 19107518
TI  - Trampoline-related injuries in childhood.
AB  - Recommendations to prevent trampoline injuries were given since the 1970s.
      However, despite these educational efforts, safety recommendations seem to be
      ignored and the number of trampoline injuries is increasing. All children
      referred to our department for injuries related to trampolines over a period of 3
      years were included. The patients' records were reviewed and a questionnaire was
      sent out in order to gain additional information. Injuries were classified as
      severe and mild. A total of 265 children (46% m, 54% f) with a median age of 8.2
      years (range 1 to 14) were included. The injury rate was continuously growing
      from the year 2005 (10.6%) to 2007 (58.1%). Most of the injuries were recorded
      between April and September with a peak of injuries in August. Seventy-five
      percent of all accidents happened in the afternoon; 40% of the injuries were
      classified as severe, 60% as mild. Nets or equal security devices were used in
      56.6%. Trampolining is associated with a significant risk for bodily harm at any
      age and results in severe injuries in 40% of cases. Though there may be still
      room for improvement in safety recommendations, all attempts over a period of
      more than 30 years to reduce the number of trampoline-related backyard injuries
      failed and the incidence is still increasing. At present, trampolines cannot be
      made safe for recreational activities and are of an unacceptable risk even under
      supervision.

PMID- 19107519
TI  - Toxicity of daily low dose cisplatin in radiochemotherapy for locally advanced
      head and neck cancer.
AB  - PURPOSE: To evaluate toxicity of radiochemotherapy schedule using daily-low-dose
      cisplatin in radiochemotherapy of locally-advanced head-and-neck-cancer (HNSCC).
      METHODS AND PATIENTS: From October 2003 to October 2006, 50 patients with HNSCC
      (stage III/IVA/IVB) were treated. In 32 patients, surgery and adjuvant
      radiotherapy(64 Gy), in 18 patients definitive radiotherapy(70 Gy) was performed.
      Low-dose-cisplatin was applied concomitantly (6 mg/m2/every radiotherapy-day).
      RESULTS: Acute toxicity > or =grade 3 was observed in 22 patients (11 patients
      mucositis/dysphagia, 7 hematologic toxicity, 4 mucositis/dysphagia/hematologic
      toxicity). 90% of our patients received >80% of the planned cumulative
      chemotherapy dose, 94% the intended dose of radiotherapy. After median follow-up
      of 24.2 months, 3-year overall survival and loco-regional control rates were 67.1
      and 78%. During follow-up, chronic toxicity > or =grade 3 (xerostomia,
      subcutaneous fibrosis, or lymphedema) was observed in nine patients. CONCLUSION:
      We found chemoradiation with daily-low-dose-cisplatin to be feasible with
      advantage of low acute and chronic toxicity. Therefore, use of low-dose-cisplatin
      should be evaluated in future clinical trials.

PMID- 19107520
TI  - Phospho-mTOR and phospho-4EBP1 in endometrial adenocarcinoma: association with
      stage and grade in vivo and link with response to rapamycin treatment in vitro.
AB  - PURPOSE: Endometrial adenocarcinoma, due to a frequent activation of PI3 K/AKT
      has been proposed as a candidate neoplasm for the treatment with mTOR inhibitors.
      Yet, data on the expression of mTOR cascade components in endometrial cancer are
      lacking. METHODS: To provide a basis for futher studies with mTOR inhibitors, we
      used immunohistochemistry to evaluate the expression of activated mTOR pathway
      components in 57 endometrial cancer surgical specimens in vivo, and investigated
      in vitro the relation between the activation of AKT/mTOR and the response to
      rapamycin. RESULTS: p-mTOR expression was associated with nuclear p-4EBP1
      expression (P = 0.02), and was more frequent in tumors extending ouside the
      uterine corpus (P = 0.011). Nuclear p-4EBP1 expression was increased in
      carcinomas of poor differentiation (P = 0.012). In cultivated PTEN-deficient
      Ishikawa cells, in addition to an activation of AKT, a phosphorylation of mTOR
      and 4EBP1 was evident, while PTEN-wild type HEC-1A cells lacked AKT activation
      but revealed a reduced expression of p-mTOR and p-4EBP1. Rapamycin induced a
      growth reduction, which was clearly more pronounced in Ishikawa cells than in HEC
      1A cells (P < 0.03) and could be observed for up to 6 days. CONCLUSISONS:
      Expression of mTOR and 4EBP1 characterize high-grade, high-stage endometrial
      adenocarcinomas and might be predictive markers of a response to rapamycin. Based
      on our results, we suggest that the expression of elements of the mTOR pathway in
      human tumor tissue should be further evaluated as a possible predictive marker in
      large-scale clinical studies as well as translational research protocols in
      clinical studies with mTOR inhibitors.

PMID- 19107521
TI  - Experimental ELISA for diagnosis of ovine dicrocoeliosis and application in a
      field survey.
AB  - Dicrocoeliosis is a parasitic disease caused by trematodes belonging to the genus
      Dicrocoelium. It usually produces mild symptoms, and for this reason,
      dicrocoeliosis often remains undetected. Its diagnosis is mostly based on
      postmortem examination of the liver or on coprological assays for in vivo
      diagnosis. However, the latter method has scant sensitivity and because of the
      long pre-patency of Dicrocoelium spp. only permits late diagnosis. In the present
      study, an enzyme-linked immunosorbent assay (ELISA) was developed based on
      excretory/secretory antigen of Dicrocoelium dendriticum. The ELISA detected
      antibodies (IgG) in experimental infected sheep starting from day 30 post
      infection (d.p.i.), whereas coprological samples were positive from 58 d.p.i. The
      ELISA was used in a field study in order to assess dicrocoeliosis seroprevalence
      in ovine flocks from the province of Trento (northeastern Italy), and this was
      the first sero-epidemiological study of ovine dicrocoeliosis in northern Italy.
      Altogether, 842 sheep sera were tested. In accordance with previous surveys
      carried out in other regions of Italy, a high prevalence of 80% to 100% was
      found.

PMID- 19107522
TI  - Analysis of the 24-h microfilarial periodicity of Mansonella perstans.
AB  - The Mansonella perstans microfilarial (mf) periodicity in peripheral blood was
      analysed in a group of 32 healthy individuals from an endemic community in
      Uganda. The majority of individuals had maximum mf intensity during the first and
      minimum during the last 12 h of the day. Mean mf ratios (i.e. time-specific
      counts in relation to mean count for the individual) indicated a weak but
      significant diurnal periodicity with peak intensity around 0800 h. Trigonometric
      analysis of the ratios, assuming a harmonic wave pattern of periodicity, gave a
      periodicity index of 11.1 and a peak time of 0645 h. The higher mf intensities in
      the early morning appeared to coincide with the preferred biting hour of the
      vectors. The observed weak pattern of mf periodicity indicates that the sampling
      time of blood specimens for diagnosis will have only minor effect on diagnostic
      sensitivity.

PMID- 19107523
TI  - Alternate spore stages of Myxobilatus gasterostei, a myxosporean parasite of
      three-spined sticklebacks (Gasterosteus aculeatus) and oligochaetes (Nais
      communis).
AB  - Two spore stages in the life cycle of Myxobilatus gasterostei, a ubiquitous
      myxosporean parasite of three-spined sticklebacks, were identified by matching
      small subunit ribosomal RNA gene sequences of actinospores from a worm with
      myxospores from fish. A Nais communis oligochaete collected in the Willamette
      River, Oregon, USA was found to produce a triactinomyxon-type actinospore which
      was distinguishable from previous records by its large size (approximately 500
      microm across) and number of germ cells (approximately 500). Its small subunit
      ribosomal RNA gene sequence was >99% similar to M. gasterostei from Europe. Two
      of ten sticklebacks from the Willamette had renal infections with Myxobilatus
      myxospores which were smaller than the type description of M. gasterostei Parisi
      (1912) but were consistent with subsequent records. Primer Mg1097r was designed
      to selectively amplify M. gasterostei in the presence of another common kidney
      myxosporean, Sphaerospora elegans. DNA sequences of spores from the fish were
      identical to each other and were 99.8% similar over 2,112 nt to the spores from
      the oligochaete. The 0.2% sequence divergence comprised polymorphisms at five
      loci, which suggested that multiple alleles were present in the parasite
      population. This is the first Myxobilatus species shown to have two spore stages
      in its life cycle and to infect an invertebrate. The infected oligochaete
      underwent paratomic fission to produce two daughter worms with parasite stages in
      their intestinal epithelia, which suggested that M. gasterostei may be sustained
      and dispersed within the invertebrate host population.

PMID- 19107524
TI  - New malaria parasites of the subgenus Novyella in African rainforest birds, with
      remarks on their high prevalence, classification and diagnostics.
AB  - Blood samples from 655 passerine birds were collected in rainforests of Ghana and
      Cameroon and examined both by microscopy and polymerase chain reaction (PCR)
      based techniques. The overall prevalence of Plasmodium spp. was 46.6%, as
      determined by combining the results of both these diagnostic methods. In
      comparison to PCR-based diagnostics, microscopic examination of blood films was
      more sensitive in determining simultaneous infection of Plasmodium spp., but both
      detection methods showed similar trends of prevalence of malaria parasites in the
      same study sites. Plasmodium (Novyella) lucens n. sp., Plasmodium (Novyella)
      multivacuolaris n. sp. and Plasmodium (Novyella) parahexamerium n. sp. were found
      in the olive sunbird Cyanomitra olivacea (Nectariniidae), yellow-whiskered
      greenbul Andropadus latirostris (Picnonotidae), and white-tailed alethe Alethe
      diademata (Turdidae), respectively. These parasites are described based on the
      morphology of their blood stages and a segment of the mitochondrial cytochrome b
      (cyt b) gene, which can be used for molecular identification and diagnosis of
      these species. Illustrations of blood stages of new species are given, and
      phylogenetic analysis identifies DNA lineages closely related to these parasites.
      Malaria parasites of the subgenus Novyella with small erythrocytic meronts
      clearly predominate in African passerines. It is probable that the development of
      such meronts is a characteristic feature of evolution of Plasmodium spp. in
      African rainforest birds. Subgeneric taxonomy of avian Plasmodium spp. is
      discussed based on the recent molecular phylogenies of these parasites. It is
      concluded that a multi-genome phylogeny is needed before revising the current
      subgeneric classification of Plasmodium. We supported a hypothesis by Hellgren,
      Krizanauskiene, Valkiunas, Bensch (J Parasitol 93:889-896, 2007), according to
      which, haemosporidian species with a genetic differentiation of over 5% in
      mitochondrial cyt b gene are expected to be morphologically differentiated. This
      study emphasises the importance of employing both PCR-based and microscopic
      methods in taxonomic, ecological and evolutionary investigations of avian
      haemosporidian parasites.

PMID- 19107525
TI  - Identifying novel genes involved in both deer physiological and human
      pathological osteoporosis.
AB  - Osteoporosis attacks 10% of the population worldwide. Humans or even the model
      animals of the disease cannot recover from porous bone. Regeneration in skeletal
      elements is the unique feature of our newly investigated osteoporosis model, the
      red deer (Cervus elaphus) stag. Cyclic physiological osteoporosis is a
      consequence of the annual antler cycle. This phenomenon raises the possibility to
      identify genes involved in the regulation of bone mineral density on the basis of
      comparative genomics between deer and human. We compare gene expression activity
      of osteoporotic and regenerating rib bone samples versus autumn dwell control in
      red deer by microarray hybridization. Identified genes were tested on human
      femoral bone tissue from non-osteoporotic controls and patients affected with age
      related osteoporosis. Expression data were evaluated by Principal Components
      Analysis and Canonical Variates Analysis. Separation of patients into a normal
      and an affected group based on ten formerly known osteoporosis reference genes
      was significantly improved by expanding the data with newly identified genes.
      These genes include IGSF4, FABP3, FABP4, FKBP2, TIMP2, TMSB4X, TRIB, and members
      of the Wnt signaling. This study supports that extensive comparative genomic
      analyses, here deer and human, provide a novel approach to identify new targets
      for human diagnostics and therapy.

PMID- 19107526
TI  - Population admixture associated with disease prevalence in the Boston Puerto
      Rican health study.
AB  - Older Puerto Ricans living in the continental U.S. suffer from higher rates of
      diabetes, obesity, cardiovascular disease and depression compared to non-Hispanic
      White populations. Complex diseases, such as these, are likely due to multiple,
      potentially interacting, genetic, environmental and social risk factors.
      Presumably, many of these environmental and genetic risk factors are contextual.
      We reasoned that racial background may modify some of these risk factors and be
      associated with health disparities among Puerto Ricans. The contemporary Puerto
      Rican population is genetically heterogeneous and originated from three ancestral
      populations: European settlers, native Taino Indians, and West Africans. This
      rich-mixed ancestry of Puerto Ricans provides the intrinsic variability needed to
      untangle complex gene-environment interactions in disease susceptibility and
      severity. Herein, we determined whether a specific ancestral background was
      associated with either of four major disease outcomes (diabetes, obesity,
      cardiovascular disease, and depression). We estimated the genetic ancestry of
      1,129 subjects from the Boston Puerto Rican Health Study based on genotypes of
      100 ancestry informative markers (AIMs). We examined the effects of ancestry on
      tests of association between single AIMs and disease traits. The ancestral
      composition of this population was 57.2% European, 27.4% African, and 15.4%
      Native American. African ancestry was negatively associated with type 2 diabetes
      and cardiovascular disease, and positively correlated with hypertension. It is
      likely that the high prevalence rate of diabetes in Africans, Hispanics, and
      Native Americans is not due to genetic variation alone, but to the combined
      effects of genetic variation interacting with environmental and social factors.

PMID- 19107527
TI  - Tracheostomized patients care: efficacy of a brief theoretical education program
      for nursing personnel.
AB  - INTRODUCTION: Tracheostomized cancer patients require a special nursing care
      involving specifically related procedures. The goal of this study was to evaluate
      the results of a brief theoretical education program on tracheostomized patients
      care for nursing personnel. MATERIALS AND METHODS: One hundred and ten
      professionals have participated in this before and after-intervention one group
      study, and the program was carried out in a Brazilian hospital, a national
      reference center in oncology treatment. The questionnaire outcomes were compared
      to assess the theoretical knowledge level of the participants. RESULTS AND
      DISCUSSION: Statistical analysis showed that this program was efficient to
      enhance knowledge skills on specific nursing procedures related to care of the
      traqueostomized cancer patients. The low costs and simple structure required in
      the program may encourage the spread of similar practices to improve quality of
      nursing assistance in the hospital environment.

PMID- 19107528
TI  - The effect of intra-operative skeletal (skull femoral) traction on apical
      vertebral rotation.
AB  - The study design is a retrospective review of consecutive case series. Our goal
      was to identify and quantify the effect of skeletal traction on the apical
      vertebral rotation (AVR). Intra-operative skeletal traction has been used for the
      correction of large magnitude idiopathic and neuromuscular scoliosis. The ability
      of skeletal traction to correct the rotational deformity of the spine has not
      been characterized. Following REB approval, retrospective analysis of 22 (AIS =
      14, neuromuscular = 8) consecutive pediatric patients having surgical posterior
      instrumented correction and fusion for their scoliosis was performed. Intra
      operative skeletal traction with approximately 50% body weight was achieved with
      smooth distal femoral pins. Counter-traction up to 25% was used through Gardner
      Wells tongs. The AVR of the major curve was assessed using the Nash-Moe grading
      system by a radiologist and a senior spine surgeon not involved in the treatment
      of these cases. Statistical analysis was performed to determine the significance.
      The overall mean AVR of the major structural curve was 3.1 +/- 0.8 and reduced to
      2.4 +/- 0.6 (p = 0.0001) following traction. The AVR decreased by one or more
      Nash-Moe grades with traction in 14/22 (64%) patients. The Cobb angle corrected
      from a mean of 88.2 degrees to 49.1 degrees (44.3%, p = 0.00001) with traction.
      The decrease in AVR correlated with the higher magnitude Cobb angles (correlation
      0.53, p = 0.014). Patients with pre-traction AVR > or = 3 showed the largest
      change with traction (3.4-2.5, p = 0.000004). There was very good association
      between the radiologist and the spine surgeon, 0.72(standing films) and
      0.63(traction films). The minor structural curve corrected from a mean Cobb of
      53.5 degrees to 33.8 degrees (37.8%) with AVR decreasing from a mean of 1.9 to
      1.4 (p = 0.014). Significant apical derotation occurs with the use of intra
      operative skull-skeletal traction in the correction of high magnitude scoliotic
      curves. This derotation can facilitate spinal exposure, placement of pedicles
      screws and final correction in these patients.

PMID- 19107530
TI  - A clinical comparison of autogenous bone graft with and without autogenous
      periodontal ligament graft in the treatment of periodontal intrabony defects.
AB  - The aim of the present study was to evaluate the efficacy of autogenous bone
      graft (ABG) with and without autogenous periodontal ligament graft (PDLG) in the
      management of human two-wall intrabony periodontal defects. Twenty-six similar
      two-wall intrabony periodontal defects with >or=5 mm probing depths and >or=3 mm
      depths of intrabony component in 13 nonsmoking healthy patients were selected.
      One defect in each subject was treated with ABG alone (ABG group) and the
      contralateral one with ABG and PDLG (PDLG group). The primary outcomes of the
      study included changes in clinical probing depth (CPD) and clinical attachment
      level (CAL). Groups showed statistically significant improvements in soft and
      hard tissue parameters after 6 months. However, the between-group differences
      after 6 months were not statistically significant with regard to soft and hard
      tissue measurements except CAL gain. In the combined group, it was significantly
      higher than the ABG group (3.69 and 2 mm, respectively; P = 0.03). Within the
      limits of this study, both treatments resulted in marked clinical improvement,
      but combined treatment seemed to enhance the results in the treatment of two-wall
      intrabony defects.

PMID- 19107531
TI  - Gaze following and gaze priming in lemurs.
AB  - Although primates have often been found to co-orient visually with other
      individuals, members of these same species have usually failed to use co
      orientation to find hidden food in object-choice experiments. This presents an
      evolutionary puzzle: what is the function of co-orientation if it is not used for
      a function as basic as locating resources? Co-orientation responses have not been
      systematically investigated in object-choice experiments, and requiring co
      orientation with humans (as is typical in object-choice tasks) may underestimate
      other species' abilities. Using an object-choice task with conspecific models
      depicted in photographs, we provide experimental evidence that two lemur species
      (Eulemur fulvus, n = 4, and Eulemur macaco, n = 2) co-orient with conspecifics.
      Secondly, by analysing together two measures that have traditionally been
      examined separately, we show that lemurs' gaze following behaviour and ultimate
      choice are closely linked. Individuals were more likely to choose correctly after
      having looked in the same direction as the model, and thus chose objects
      correctly more often than chance. We propose a candidate system for the
      evolutionary origins of more complex gaze following: 'gaze priming.'

PMID- 19107533
TI  - A reaction-diffusion model for long bones growth.
AB  - Bone development is characterized by differentiation and growth of chondrocytes
      from the proliferation zone to the hypertrophying one. These two cellular
      processes are controlled by a complex signalling regulatory loop between
      different biochemical signals, whose production depends on the current cell
      density, constituting a coupled cell-chemical system. In this work, a
      mathematical model of the process of early bone growth is presented, extending
      and generalizing other earlier approaches on the same topic. A reaction-diffusion
      regulatory loop between two chemical factors: parathyroid hormone-related peptide
      (PTHrP) and Indian hedgehog (Ihh) is hypothesized, where PTHrP is activated by
      Ihh and inhibits Ihh production. Chondrocytes proliferation and hypertrophy are
      described by means of population equations being both regulated by the PTHrP and
      Ihh concentrations. In the initial stage of bone growth, these two cellular
      proceses are considered to be directionally dependent, modelling the well known
      column cell formation, characteristic of endochondral ossification. This coupled
      set of equations is solved within a finite element framework, getting an
      estimation of the chondrocytes spatial distribution, growth of the diaphysis and
      formation of the epiphysis of a long bone. The results obtained are qualitatively
      similar to the actual physiological ones and quantitatively close to some
      available experimental data. Finally, this extended approach allows finding
      important relations between the model parameters to get stability of the
      physiological process and getting additional insight on the spatial and
      directional distribution of cells and paracrine factors.

PMID- 19107534
TI  - Enhanced inulinase production in solid state fermentation by a mutant of the
      marine yeast Pichia guilliermondii using surface response methodology and inulin
      hydrolysis.
AB  - In order to isolate inulinase overproducers of the marine yeast Pichia
      guilliermondii, strain 1, cells were mutated by using UV light and LiCl(2). One
      mutant (M-30) with enhanced inulinase production was obtained. Response surface
      methodology (RSM) was used to optimize the medium compositions and cultivation
      conditions for inulinase production by the mutant in solid-state fermentation.
      The initial moisture, inoculum, the amount ratio of wheat bran to rice bran,
      temperature, pH for the maximum inulinase production by the mutant M-30 were
      found to be 60.5%, 2.5%, 0.42, 30 degrees C and 6.50, respectively. Under the
      optimized conditions, 455.9 U/grams of dry substrate (gds) of inulinase activity
      was reached in the solid state fermentation culture of the mutant M-30 whereas
      the predicted maximum inulinase activity of 459.2 U/gds was derived from RSM
      regression. Under the same conditions, its parent strain only produced 291.0
      U/gds of inulinase activity. This is the highest inulinase activity produced by
      the yeast strains reported so far.

PMID- 19107532
TI  - Insulin regulates milk protein synthesis at multiple levels in the bovine mammary
      gland.
AB  - The role of insulin in milk protein synthesis is unresolved in the bovine mammary
      gland. This study examined the potential role of insulin in the presence of two
      lactogenic hormones, hydrocortisone and prolactin, in milk protein synthesis.
      Insulin was shown to stimulate milk protein gene expression, casein synthesis and
      (14)C-lysine uptake in mammary explants from late pregnant cows. A global
      assessment of changes in gene expression in mammary explants in response to
      insulin was undertaken using Affymetrix microarray. The resulting data provided
      insight into the molecular mechanisms stimulated by insulin and showed that the
      hormone stimulated the expression of 28 genes directly involved in protein
      synthesis. These genes included the milk protein transcription factor, ELF5,
      translation factors, the folate metabolism genes, FOLR1 and MTHFR, as well as
      several genes encoding enzymes involved in catabolism of essential amino acids
      and biosynthesis of non-essential amino acids. These data show that insulin is
      not only essential for milk protein gene expression, but stimulates milk protein
      synthesis at multiple levels within bovine mammary epithelial cells.

PMID- 19107535
TI  - Lactose mother liquor as an alternative nutrient source for microbial concrete
      production by Sporosarcina pasteurii.
AB  - Microbiologically induced calcite precipitation by the bacterium Sporosarcina
      pasteurii (NCIM 2477) using the industrial effluent of the dairy industry,
      lactose mother liquor (LML) as growth medium was demonstrated for the first time
      in this study. The urease activity and the calcite precipitation by the bacterium
      was tested in LML and compared with the standard media like nutrient media and
      yeast extract media. Calcite constituted 24.0% of the total weight of the sand
      samples plugged by S. pasteurii and urease production was found to be 353 U/ml in
      LML medium. The compressive strength of cement mortar was increased by S.
      pasteurii in all the media used compared to control. No significant difference in
      the growth, urease production and compressive strength of mortar among the media
      suggesting LML as an alternative source for standard media. This study
      demonstrates that microbial calcite acts as a sealing agent for filling the gaps
      or cracks and fissures in constructed facilities and natural formations alike.

PMID- 19107536
TI  - Imaging E-selectin expression following traumatic brain injury in the rat using a
      targeted USPIO contrast agent.
AB  - INTRODUCTION: The aim of this work was to map E-selectin expression in a
      traumatic brain injury model using a newly-designed MR contrast agent. Iron
      cores, responsible for susceptibility effects and therefore used as T2* contrast
      agents, need to be coated in order to be stabilized and need to be targeted to be
      useful. METHODS: We have designed a molecule coating composed, at one end, of
      bisphosphonate to ensure anchorage of the coating on the iron core and, at the
      other end, of Fukuda's defined heptapeptide known to target selectin binding
      sites. CONCLUSION: The synthesized nanoparticles were able to non-invasively
      target the traumatic brain lesion, inducing a specific T2* decrease of about 25%
      up to at least 70 min post-injection of the targeted contrast agent.

PMID- 19107537
TI  - Monitoring kidney and renal cyst volumes applying MR approaches on a rapamycin
      treated mouse model of ADPKD.
AB  - OBJECT: The aim of our study was to determine total cystic volume in a mouse
      model of PKD using MR imaging to monitor therapeutic effects in vivo. MATERIALS
      AND METHODS: We imaged eight female pcy-mice in two groups: four belonged to an
      untreated control group and four were treated with the anticystic agent
      rapamycin, which has proven to be effective in reducing cystogenesis in animal
      models. The mice were imaged using a 9.4 Tesla animal scanner. MRI measurements
      were taken at six time points during the therapy. Total renal volumes and total
      cyst volumes were calculated using a thresholding approach. RESULTS: During the
      course of the treatment, the total cyst volume increased significantly faster
      than the total renal volume in the untreated group, indicating that growth of the
      total renal volume in the untreated group was primarily due to the growth of the
      cysts, rather than the parenchyma. The measured total renal volume in the control
      (placebo) group was significantly higher than the volume in the treated group.
      CONCLUSION: Using MRI, we were able to monitor the cystic volume in a mouse model
      of PKD to assess the therapeutic effect of anticystic treatment.

PMID- 19107538
TI  - An animal model of oral dysphagia in amyotrophic lateral sclerosis.
AB  - Relatively little is known about the underlying neuropathology of dysphagia in
      amyotrophic lateral sclerosis (ALS); thus, effective treatments remain elusive.
      Tremendous progress toward understanding and treating dysphagia in ALS may be
      possible through the use of an animal model of dysphagia in ALS research;
      however, no such animal model currently exists. The most logical candidate to
      consider is the SOD1-G93A transgenic mouse, the most widely investigated animal
      model of ALS. To investigate whether this animal model develops dysphagia, oral
      behaviors (lick and mastication rates) of SOD1-G93A transgenic mice (n = 30) were
      evaluated at three time points based on hind limb motor function: asymptomatic
      (60 days), disease onset (approximately 110 days), and disease end-stage
      (approximately 140 days). Age-matched nontransgenic littermates (n = 30) served
      as controls. At each time point, lick and mastication rates were significantly
      lower (p < 0.05) for transgenic mice compared with controls. Histologic analysis
      of the brainstem showed marked neurodegeneration (vacuolation) of the trigeminal
      and hypoglossal nuclei, two key motor components involved in mastication and
      licking behaviors. These results demonstrate a clinicopathologic correlation of
      oral dysfunction in SOD1-G93A transgenic mice, thereby establishing the SOD1-G93A
      transgenic mouse as a bona fide animal model of oral dysphagia in ALS.

PMID- 19107539
TI  - Excitable population dynamics, biological control failure, and spatiotemporal
      pattern formation in a model ecosystem.
AB  - Biological control has been attracting an increasing attention over the last two
      decades as an environmentally friendly alternative to the more traditional
      chemical-based control. In this paper, we address robustness of the biological
      control strategy with respect to fluctuations in the controlling species density.
      Specifically, we consider a pest being kept under control by its predator. The
      predator response is assumed to be of Holling type III, which makes the system's
      kinetics "excitable." The system is studied by means of mathematical modeling and
      extensive numerical simulations. We show that the system response to
      perturbations in the predator density can be completely different in spatial and
      non-spatial systems. In the nonspatial system, an overcritical perturbation of
      the population density results in a pest outbreak that will eventually decay with
      time, which can be regarded as a success of the biological control strategy.
      However, in the spatial system, a similar perturbation can drive the system into
      a self-sustained regime of spatiotemporal pattern formation with a high pest
      density, which is clearly a biological control failure. We then identify the
      parameter range where the biological control can still be successful and describe
      the corresponding regime of the system dynamics. Finally, we identify the main
      scenarios of the system response to the population density perturbations and
      reveal the corresponding structure of the parameter space of the system.

PMID- 19107540
TI  - "Everything I know I learned from my mother...Or not": perspectives of African
      American and white women on decisions about tubal sterilization.
AB  - BACKGROUND: African-American women have had higher rates of female sterilization
      compared to white women since its emergence as a contraceptive method. The
      reasons underlying this observed racial difference are unknown. OBJECTIVES: The
      goals of this study were to (1) explore what factors shape black and white
      women's decisions about tubal sterilization as a contraceptive method and (2)
      generate hypotheses about the relationship of race to the decision-making
      process. DESIGN: We conducted six focus groups stratified by tubal sterilization
      status and race. During each of the audio-recorded sessions, participants were
      asked to discuss reasons that women choose sterilization as a contraceptive
      method. PARTICIPANTS: The participants of the study were 24 African-American
      women and 14 white women. APPROACH: Transcripts of the sessions were
      qualitatively analyzed with particular attention to factors that might be unique
      to each of the two racial groups. RESULTS: Personal factors shaped black and
      white women's decisions regarding tubal sterilization. Preference for a
      convenient, highly effective contraceptive method was the main reason to get a
      tubal sterilization for women of both racial groups. We also identified socio
      cultural differences that might explain why black women are more likely than
      white women to choose tubal sterilization over other contraceptive methods. An
      unanticipated, but clinically important, finding was that women often reported
      feeling that their doctors and the health-care system served as barriers to
      obtaining the desired procedure. CONCLUSION: Socio-cultural differences may help
      explain why black and white women choose different contraceptive methods.

PMID- 19107561
TI  - Socioeconomic status in relation to early menarche among black and white girls.
AB  - OBJECTIVE: Early menarche is a risk factor for breast cancer. We investigated the
      variation in age at menarche by socioeconomic status (SES) and race. METHODS: A
      cohort study was conducted on 1,091 black and 986 white girls from the three
      sites in the United States as part of the NHLBI Growth and Health Study (NGHS),
      who were aged 9-10 years at baseline and followed through adolescence over a 10
      year period with annual exams. Using logistic regression models, we evaluated the
      nature and strength of associations between two socioeconomic indicators
      (household income and parental education) and early menarche (<12 years old)
      unadjusted and adjusted for anthropometry and maternal age at menarche. RESULTS:
      Proportionately, more black girls were menarcheal before 12 years of age compared
      to their white counterparts (46%, n = 468 vs. 26%, n = 240, respectively, p <
      0.0001). Parental education was not a significant predictor of early menarche.
      The graded association between household income and age at menarche was strong
      and significant among black girls but less clear among white girls. Compared with
      those in the lowest quartile of household income, white girls in the highest
      quartile were at a significantly lower risk of early menarche [adjusted odds
      ratio (OR) = 0.37, 95% confidence intervals (CIs) 0.18-0.80]. The inverse was
      true for black girls: those in the highest quartile of household income were at
      an increased risk of early menarche (adjusted OR = 2.15, 95% CI 1.27-3.63)
      CONCLUSION: The SES factor selected (household income versus parental education)
      affected the findings regarding racial differences in the timing of menarche. It
      will be important for future studies to elucidate the link between household
      income and age at menarche in developed countries.

PMID- 19107562
TI  - Assessment of availability, ecological feature, and habitat preference of the
      medicinal herb Houttuynia cordata Thunb in the Brahmaputra Valley of Assam,
      India.
AB  - Houttuynia cordata Thunb. is a rhizome-bearing aromatic medicinal herb and is
      restricted to specialized moist habitats. The plant is collected from natural
      habitats for local consumption and trade. The status of the species and its
      variations in physiological performance in different habitats were studied in
      selected sites of geographically different areas of Brahmaputra valley in eastern
      India. The surveys were conducted in two different growth stages of the plant
      during 2005-2007. The sites where the species was encountered were marked and a
      distribution map was prepared. The frequency and density of the plant was higher
      in the moist habitats with higher organic carbon (0.85+/-0.05%). Generally, the
      density, biomass production and growth had significant (P<0.05) positive
      relationship with the soil physicochemical properties (linear curve fit). Soil
      moisture was the most dependent factor for the plant growth and the optimum
      growth was recorded at 78+/-5.6% (r2=0.9; P<or=0.01). The physiological
      performance of the plant in all the studied sites were significantly varied
      (P<0.05). The growth and development of H. cordata were also different in the
      flowering and senescence stages. Clay loam soil, average soil pH of 5.9, and 78%
      soil moisture were the favorable soil characteristics for the better growth of H.
      cordata and, hence, these data may be considered for conservation of the species.

PMID- 19107563
TI  - Pesticide pollution of River Ghaggar in Haryana, India.
AB  - Ghaggar, one of the major rivers of northern India originating in outer Himalayas
      and flowing through the state of Punjab, Haryana, and Rajasthan, is put to
      multiple uses. Along its course of 464 km, it receives discharge from various
      cities and runoff from agricultural lands. Punjab and Haryana are two
      predominantly agricultural states of India using substantial amounts of
      agrochemicals, yet there are no reports available in literature on the level of
      pesticides in the stretch of river Ghaggar through Punjab and Haryana. This is
      the first report on pesticide pollution of the river Ghaggar in Haryana. Water
      samples along the 230-km stretch of the river in Haryana were analyzed for the
      presence of organochlorine insecticide residues. While aldrin and dieldrin were
      below detection limits, both hexachlorocyclohexane (HCH) and
      dichlorodiphenyltrichloroethane (DDT) were traceable in all the water samples.
      High concentration of beta-HCH among SigmaHCH indicates old pollution source
      whereas predominance of p,p'-DDT among SigmaDDT reflects its recent use in the
      catchment area of the river. The concentrations of HCH and DDT in all the samples
      were above the permissible limits prescribed by the European Commission Directive
      for drinking purposes.

PMID- 19107564
TI  - Determination of the level of contamination in Khuzestan coastal waters (Northern
      Persian Gulf) by using an ecological risk index.
AB  - The aims of the present study were to investigate the metal contents of sediments
      of several creeks that discharged into coastal waters using the Risk index. This
      study was carried out in eight creeks in Mahshahr coastal waters in the Northwest
      of Persian Gulf from October 2005 to November 2006. Superficial sediments were
      collected seasonally by Peterson grab, and the concentrations of heavy metals
      were measured by using a voltammetric polarographic method. The range and the
      mean concentrations obtained in ppm were 15.03-35.16 (27.01) for Cu, 65.57-171.41
      (102.67) for Ni, 4.63-20.06 (13.22) for Co, 0.093-0.78 (0.22) for Hg, 65.07-379
      (113.70) for Zn, 0.27-1.00 (0.56) for Cd and 7.09-29.72 (14.66) for Pb. To
      evaluate the levels of sediment contamination, the background values of the
      different heavy metals were calculated, and the contamination factor for each
      metal and the degree of contamination for each creek were determined as well. The
      results show that some elements such as Hg, Zn, and Ni are at risk level, and all
      of the studied creeks are classified as undergoing a moderate degree of pollution
      except for Ghannam that showed a considerable degree of contamination. According
      to the Risk index values, based on sedimentological toxic factors (S(t)) of each
      metal and the BIO Production Index (BPI) in the studied area, the creeks were
      classified as considerable and with a very high level of ecological risk.

PMID- 19107565
TI  - Spatial distribution and quantification of endocrine-disrupting chemicals in Sado
      River estuary, Portugal.
AB  - The important Portuguese Sado River estuary has never been investigated for the
      presence of potentially endocrine-disrupting chemicals (EDCs), such as natural
      estrogens (estradiol, estrone), pharmaceutical estrogens (17alpha
      ethynylestradiol), phytoestrogens (daidzein, genistein and biochanin A), or
      industrial chemicals (4-octylphenol, 4-nonylphenol, and bisphenol A). Thus, the
      main objective of this study was to evaluate their presence at 13 sampling points
      distributed between both the industrial and the natural reserve areas of the
      estuary, zones 1 and 2, respectively. For that, water samples collected in summer
      and winter were processed by solid phase extraction and analyzed by high
      performance liquid chromatography with photodiode array detection and gas
      chromatography-mass spectroscopy. Results showed that estrone, ethynylestradiol,
      all the aforementioned phytoestrogens as well as bisphenol A and 4-octylphenol
      were found in zone 1. In zone 2, neither estrogens nor 4-OP were found. However,
      in the same zone, daidzein (500 ng/L) and genistein (320 ng/L) attained their
      highest levels in summer, whereas biochanin A peaked in winter (170 ng/L).
      Furthermore, bisphenol A was also found in some areas of zone 2, but showed
      similar concentrations in both surveys (about 220 ng/L). This study demonstrated
      that the Sado River estuary had low EDCs levels, suggesting that the Sado's high
      hydrodynamic activity may be involved in the dilution of local pollution. It was
      suggested that at the current levels of concentrations, all assayed EDCs are
      unlikely to individually cause endocrine disruption in local animals. However,
      under a continuous exposure scenario, an additive and/or synergistic action of
      the estrogenic chemicals load can not be excluded, and so, continuous monitoring
      is advisable.

PMID- 19107566
TI  - An examination of the effect of landscape pattern, land surface temperature, and
      socioeconomic conditions on WNV dissemination in Chicago.
AB  - This paper developed an approach by the synthesis of remote sensing, landscape
      metrics, and statistical methods to examine the effects of landscape pattern,
      land surface temperature, and socioeconomic conditions on the spread of West Nile
      virus (WNV) caused by mosquitoes and animal hosts in Chicago, USA. Land use/land
      cover and land surface temperature images were derived from Terra's Advanced
      Spaceborne Thermal Emission and Reflection Radiometer imagery. An analytical
      procedure using landscape metrics was developed, applying configuration analysis
      of landscape patterns in the study area. The positive reports of mosquitoes and
      animal hosts for WNV in fall, 2001-2006, were collected from the Cook County
      Public Health Department. Forty-nine municipalities were found to have WNV
      positive records in mosquitoes and animal hosts in fall 2004. Socioeconomic data
      were obtained from the 2000 US Census. Statistical analysis was applied to WNV
      data in fall 2004 to identify the relationship between potential predictors and
      WNV spread. As a result, landscape factors, such as landscape aggregation index
      and the urban areas and areas of grass and water, showed strong correlations with
      the WNV-positive records. Socioeconomic conditions, such as the population over
      65 years old, also showed a strong correlation with WNV-positive records. Thermal
      conditions of water showed a less but still considerable correlation to WNV
      positive records. This research offers an opportunity to explore the effects of
      landscape pattern, land surface temperature, and socioeconomic conditions on the
      spread of WNV caused by mosquitoes and animal hosts. Results can contribute to
      public health and environmental management in the study area.

PMID- 19107567
TI  - Qualitative differences in knowledge structure are associated with diagnostic
      performance in medical students.
AB  - Diagnosing is a knowledge-based skill: to diagnose one must retrieve knowledge
      from long-term memory and then apply this to a new clinical problem. Prior
      research on expertise found differences in knowledge structure between experts
      and novices, and it is assumed that the superior diagnostic performance of
      experts is somehow related to their superior knowledge structure. Here our
      objective was to study knowledge structure in final year medical students and to
      examine the association between knowledge structure and diagnostic performance.
      Ninety-one students participated. We used concept sorting to assess knowledge
      structures for four clinical problems. We performed qualitative analysis of
      knowledge structures, categorizing these as either problem-specific, where
      knowledge was predominantly structured around concepts specific to that clinical
      problem, or generic, where knowledge was structured around general concepts that
      could apply to all clinical problems. We evaluated diagnostic performance using
      problem-solving questions. Knowledge structure varied between different problems,
      but for each problem most students had problem-specific knowledge structure.
      These students had better diagnostic performance than those with generic
      structure (68.5 vs. 55.3%, d = 0.45, P = 0.004). This difference persisted after
      adjusting for overall medical knowledge (performance on the Medical Council of
      Canada Part 1 examination) and clinical problem. We found that most students
      organize their knowledge around problem-specific concepts, and that this type of
      knowledge was associated with better diagnostic performance. This may be due to
      easier knowledge retrieval if there is congruence between how knowledge is stored
      and how it is applied when diagnosing.

PMID- 19107568
TI  - An analysis of socio-economic and environmental sustainability of goat production
      in the Taurus Mountain Villages in the Eastern Mediterranean Region of Turkey,
      with consideration of gender roles.
AB  - This paper aims to reveal socio-economic and environmental sustainability of goat
      production in the Taurus Mountains' villages in Eastern Mediterranean region of
      Turkey: with consideration of gender roles. Goat production sector is the most
      important livelihood activity in the Mediterranean region of Turkey. According to
      various new regulations of the Ministry of Forestry, goat production in the
      mountainous villages of Taurus Mountains has been banned for recent year for
      various reasons such as; the destruction of shoots and branches in trees, forest
      degradation and erosion. Therefore, goat production is decreasing dramatically in
      that region. Data were collected in 4 districts of 8 villages in which goat
      production has been done intensively (two villages in each district) by face to
      face interview with 52 women and 58 men. Data were analyzed in Statistical
      Program of Social Science (SPSS). According to our findings, goat production has
      different affects on the lives of men and women and the sustainability of the
      sector is dependent on social factors, primarily education.

PMID- 19107569
TI  - Feed supplementation prevents post-conception decline in milk progesterone
      concentrations associated with production stress in dairy buffaloes (Bubalus
      bubalis).
AB  - The onset of pregnancy may be associated with hormonal changes and decline in
      milk yield of buffaloes. To investigate this, forty lactating buffaloes from 1st
      to 23rd weeks post-conception were selected. The animals were assigned to three
      treatments: PRT, PRS, NPRT and three milk yielding groups HMY, 66 to 75 l/week, n
      = 12; MMY, 56 to 65 l/week, n = 16; LMY, 46 to 55 l/week, n = 12). Milk samples
      were collected on alternate weeks and analyzed with ultrasonic milk analyzer. EIA
      was used for milk progesterone concentrations. Group means were compared and
      correlation analysis was conducted. Progesterone concentrations increased in
      almost similar pattern with the advancing weeks post-conception. The high and low
      yielder showed greater progesterone concentrations in the supplemented than the
      animals on traditional ration (P < 0.001). Progesterone concentrations correlated
      positively with fat (%), negatively with milk yield, protein (%) and lactose (%).
      Decline in milk yield became drastic when progesterone concentrations rose above
      6.44 ng/ml. The pregnant animals on traditional ration exhibited a sharper
      decline in milk yield with the increasing progesterone concentrations as compared
      to pregnant animals with supplemented ration. It is concluded that concentrates
      supplementation induced a raise in progesterone levels. Progesterone
      concentrations and milk yield showed an inverse relationship.

PMID- 19107570
TI  - A novel mutation in NDUFS4 causes Leigh syndrome in an Ashkenazi Jewish family.
AB  - Leigh syndrome is a neurodegenerative disorder of infancy or childhood generally
      due to mutations in nuclear or mitochondrial genes involved in mitochondrial
      energy metabolism. We performed linkage analysis in an Ashkenazi Jewish (AJ)
      family without consanguinity with three affected children. Linkage to
      microsatellite markers D5S1969 and D5S407 led to evaluation of the complex I gene
      NDUFS4, in which we identified a novel homozygous c.462delA mutation that
      disrupts the reading frame. The resulting protein lacks a cAMP-dependent protein
      kinase phosphorylation site required for activation of mitochondrial respiratory
      chain complex I. In a random sample of 5000 healthy AJ individuals, the carrier
      frequency of the NDUFS4 mutation c.462delA was 1 in 1000, suggesting that it
      should be considered in all AJ patients with Leigh syndrome.

PMID- 19107571
TI  - The phenotypic spectrum of paediatric neurotransmitter diseases and infantile
      parkinsonism.
AB  - Paediatric neurotransmitter diseases are a group of inherited disorders
      attributable to a disturbance of neurotransmitter metabolism. The monoamines,
      catecholamines and serotonin, also called biogenic amines, are neurotransmitters
      with multiple roles including psychomotor function, hormone secretion,
      cardiovascular, respiratory and gastrointestinal control, sleep mechanisms, body
      temperature and pain. Given the multiple functions of monoamines, disorders of
      their metabolism comprise a wide spectrum of manifestations, with motor
      dysfunction being the most prominent clinical feature. The severity of the
      clinical manifestations ranges from mild to severe. Patients with severe and
      intermediate phenotypes may present with infantile parkinsonism that differs in a
      number of aspects from the parkinsonism in nigrostriatal degeneration. Analysis
      of monoamine metabolites and pterins in spinal fluid assists in the diagnosis of
      these disorders. Treatment options include tetrahydrobiopterin supplementation,
      L: -dopa, 5-hydroxytryptophan, and medications that potentiate monoamine
      transmission. Response to treatment is variable.

PMID- 19107572
TI  - Early detection of myocardial dysfunction in children with beta-thalassaemia
      major.
AB  - To evaluate left and right ventricular myocardial performance using pulsed-tissue
      Doppler imaging (TDI) and its relation to BNP levels in patients with beta
      thalassaemia major (beta-TM). We enrolled 36 thalassaemic patients (21 male, 15
      female; mean age: 14.2 +/- 4.1 years) with normal left ventricular systolic and
      diastolic functions with conventional echocardiography and 30 healthy control
      subjects (18 male, 12 female, and 12.5 +/- 4.2 years). Myocardial performance
      indexes (MPI) of left ventricular (LV) lateral wall, interventricular septum
      (IVS) and right ventricular (RV) lateral wall were calculated with TDI. Plasma
      BNP levels were measured in all patients. MPIs and other echocardiographic
      parameters of patients with beta-TM were compared with control group. All the
      patients' plasma BNP levels were within normal limits. There were no differences
      between conventional echocardiographic parameters of patients and control group.
      MPI of LV, IVS, and RV of patients were significantly higher than control group
      (P = 0.01, and P < 0.01, and P < 0.001, respectively). Our study confirms that
      MPI obtained by TDI seems to be an early sensitive parameter of cardiac
      dysfunction in beta-TM. We concluded that MPI obtained by TDI may be an
      adjunctive parameter to conventional echocardiography for detecting early
      myocardial damage.

PMID- 19107573
TI  - Estrogen regulates DNA methyltransferase 3B expression in Ishikawa endometrial
      adenocarcinoma cells.
AB  - It is well-known that exposure to unopposed estrogen is considered as an
      important risk factor for endometrial cancer. Recent studies have shown that over
      expression of DNA methyltransferases (DNMTs) are involved in the development of
      endometrial cancer. Therefore, the present study was undertaken to elucidate the
      impact of estrogen on the expression of DNMTs in endometrial cancer. Ishikawa
      cell line was used. Flow cytometry analysis demonstrated that 17 beta-estradiol
      (E(2)) enhanced the cell proliferation with a peak at 10(-8) M. Over-expression
      of DNMT3B treated with E(2) was confirmed by real-time PCR and western blotting
      analysis. Furthermore, the up-regulation of DNMT3B expression induced by E(2) was
      suppressed by the addition of ICI182780. However, we did not observe changes in
      the expression of DNMT1. Our study suggests that estrogen up-regulating the
      expression of DNMT3B in an ER-dependent pathway may be a possible mechanism for
      estrogen facilitates the malignant transformation of endometrial cancer cells.

PMID- 19107574
TI  - Effect of high glucose concentration on VEGF and PEDF expression in cultured
      retinal Muller cells.
AB  - To explore the effect of high glucose concentration on the expression of vascular
      endothelial growth factor (VEGF) and pigment epithelium derived factor (PEDF) in
      the cultured rat retinal Muller cells. Rat Muller cells were cultured and RT-PCR
      and Western-blot analysis were used to measure the levels of VEGF and PEDF in
      cultured Muller cells at different high glucose concentrations. Under 10, 20, 30
      mmol/L high glucose conditions, the levels of VEGF mRNA and protein increased and
      the levels of PEDF mRNA and protein decreased. These results suggest that the
      VEGF and PEDF expression in Muller cells are unbalance under high glucose
      concentration, which contribute to retinal neovascularization in diabetic
      retinopathy.

PMID- 19107575
TI  - Chronic exposure to exogenous matrilysin induces chemoresistance and enhances Bcl
      2 expression in A549 lung adenocarcinoma cells.
AB  - Matrix metalloproteinase (MMP) family member matrilysin (matrilysin) has been
      indicated to induce apoptosis-resistance and chemoresistance. The purpose of
      current study was to investigate the potential capacity of induction cisplatin
      resistance upon the unremitting exposure to exogenic matrilysin. At the same
      time, the expressions of apoptosis-related genes were examined to clarify the
      underlying mechanisms. A549 lung adenocarcinoma cells was used to establish our
      chronic exposure models. The viability of A549 lung adenocarcinoma cells was
      determinated by MTT and the apoptosis was assessed by Hoechst 33342 staining and
      Annexin V-FITC/PI apoptosis kit. The expressions of apoptosis-relative genes were
      evaluated by flow cytometry, immunocytochemistry staining and real-time
      quantitative RT-PCR, respectively. Overall, chronic exposure to crescenting level
      of exogenous matrilysin (10, 50, 100, 200 ng/ml) did not significantly alter the
      growth rates of A549 cells. However, a certain range of matrilysin might protect
      tumor cells from cisplatin-medicated death. The underlying mechanism may due to
      the Bcl-2 overexpression and imbalance in the ratio of Bcl-2/Bax. Our results
      offer a potential mechanism to explain the impact of matrilysin on apoptosis and
      provide new insights into the profound mechanisms of acquired cisplatin
      resistance. Further researches are highly suggestive of this association which
      has great clinical implications.

PMID- 19107576
TI  - Comparative proteomic analysis of apomictic monosomic addition line of Beta
      corolliflora and Beta vulgaris L. in sugar beet.
AB  - Apomixis refers to a process in which plants produce seed without fertilization
      through female syngamy that produces embryos genetically identical to the
      maternal parent. In sugar beet, interspecific hybrids between diploid Beta
      vulgaris and tetraploid Beta corolliflora were established and monosomic addition
      line M14 was selected because of the apomictic phenotype. By using two
      dimensional electrophoresis gels we identified the proteins which were
      differently expressed between the M14 and B. vulgaris. A total of 27 protein
      spots which varied expressed between lines were isolated and successfully
      identified with MALDI-TOF MS. Among them five protein spots were found to be only
      presented in M14 and two protein spots only expressed in Beta. According to their
      functional annotations described in Swissprot database, these proteins were,
      respectively, involved in important biological pathways, such as cell division,
      functionally classified using the KEGG functional classification system. The
      result may be useful for us to better understand the genetic mechanism of
      apomixes.

PMID- 19107578
TI  - Emerging trends in human ABC transporters.

PMID- 19107577
TI  - On the relationship between individual and population health.
AB  - The relationship between individual and population health is partially built on
      the broad dichotomization of medicine into clinical medicine and public health.
      Potential drawbacks of current views include seeing both individual and
      population health as absolute and independent concepts. I will argue that the
      relationship between individual and population health is largely relative and
      dynamic. Their interrelated dynamism derives from a causally defined life course
      perspective on health determination starting from an individual's conception
      through growth, development and participation in the collective till death, all
      seen within the context of an adaptive society. Indeed, it will become clear that
      neither individual nor population health is identifiable or even definable
      without informative contextualization within the other. For instance, a person's
      health cannot be seen in isolation but must be placed in the rich contextual web
      such as the socioeconomic circumstances and other health determinants of where
      they were conceived, born, bred, and how they shaped and were shaped by their
      environment and communities, especially given the prevailing population health
      exposures over their lifetime. We cannot discuss the "what" and "how much" of
      individual and population health until we know the cumulative trajectories of
      both, using appropriate causal language.

PMID- 19107580
TI  - Physical therapy utilization in subjects with work-related musculoskeletal
      disorders: Taiwan experience.
AB  - INTRODUCTION: This study aimed to investigate the use of physical therapy (PT)
      services by subjects with work-related musculoskeletal disorders (WMSDs) and to
      identify factors associated with long-term use of PT in Taiwan. METHODS: Data
      including demographic characteristics, work history, pain and disability ratings,
      and psychosocial status were collected by questionnaire. Subjects who were
      referred to PT were interviewed weekly by telephone to obtain information about
      use of PT. RESULTS: A total of 160 subjects participated in this study. Of these,
      85 subjects (53.1%) did not receive PT. Of the 75 subjects who received PT, 53
      (70.7%) received short-term treatment (<30 days) and 22 (29.3%) received long
      term treatment (> or =30 days). The number of treatment sessions for the
      treatment groups was 7.8 sessions +/- 9.0. Logistic regression analysis
      identified age (odds ratio [OR] = 1.074, P = 0.007) and the subject's confidence
      that the disorder would be diagnosed as an occupational injury ("yes" and "not
      sure" vs. "no"; OR = 4.288, P = 0.012) as significant factors affecting the
      duration of treatment. CONCLUSIONS: Almost 30% of the subjects referred to PT
      received long-term treatment (> or =30 days), the significant factors affecting
      this classification were subject's age and confidence in a diagnosis of WMSD.

PMID- 19107579
TI  - Methods for the preparation and manufacture of polymeric nanoparticles.
AB  - This review summarizes the different methods of preparation of polymer
      nanoparticles including nanospheres and nanocapsules. The first part summarizes
      the basic principle of each method of nanoparticle preparation. It presents the
      most recent innovations and progresses obtained over the last decade and which
      were not included in previous reviews on the subject. Strategies for the
      obtaining of nanoparticles with controlled in vivo fate are described in the
      second part of the review. A paragraph summarizing scaling up of nanoparticle
      production and presenting corresponding pilot set-up is considered in the third
      part of the review. Treatments of nanoparticles, applied after the synthesis, are
      described in the next part including purification, sterilization, lyophilization
      and concentration. Finally, methods to obtain labelled nanoparticles for in vitro
      and in vivo investigations are described in the last part of this review.

PMID- 19107581
TI  - An interface model for dosage adjustment connects hematotoxicity to
      pharmacokinetics.
AB  - When modeling is required to describe pharmacokinetics and pharmacodynamics
      simultaneously, it is difficult to link time-concentration profiles and drug
      effects. When patients are under chemotherapy, despite the huge amount of blood
      monitoring numerations, there is a lack of exposure variables to describe
      hematotoxicity linked with the circulating drug blood levels. We developed an
      interface model that transforms circulating pharmacokinetic concentrations to
      adequate exposures, destined to be inputs of the pharmacodynamic process. The
      model is materialized by a nonlinear differential equation involving three
      parameters. The relevance of the interface model for dosage adjustment is
      illustrated by numerous simulations. In particular, the interface model is
      incorporated into a complex system including pharmacokinetics and neutropenia
      induced by docetaxel and by cisplatin. Emphasis is placed on the sensitivity of
      neutropenia with respect to the variations of the drug amount. This complex
      system including pharmacokinetic, interface, and pharmacodynamic hematotoxicity
      models is an interesting tool for analysis of hematotoxicity induced by
      anticancer agents. The model could be a new basis for further improvements aimed
      at incorporating new experimental features.

PMID- 19107583
TI  - Caught in the psychiatric net: meanings and experiences of ADHD, pediatric
      bipolar disorder and mental health treatment among a diverse group of families in
      the United States.
AB  - Based on a 13-month ethnographic meaning-centered study of the lived experience
      of behavioral and emotional disorders among children and families living in the
      United States, this article highlights the range of orientations to mental health
      problems and treatment among families from diverse backgrounds. Detailed case
      portraits of three families are presented to illustrate the various meanings that
      psychiatric diagnoses and mental health treatments take on within families, with
      medicalized perspectives holding less salience among African-American families
      relative to Euro-Americans in the study. The diverse orientations to problems
      among families in the study suggest that, despite the dominance of biochemical
      and neurological explanations for behavioral and emotional distress in
      contemporary U.S. culture, and especially U.S. psychiatry, nonpathological
      interpretations have not been wholly eclipsed by broad trends toward
      biologization and medicalization. Families' experiences are positioned to reveal
      the allure, as well as the limitations, of biopsychiatric approaches to
      behavioral and emotional problems.

PMID- 19107582
TI  - Reconsidering the placebo response from a broad anthropological perspective.
AB  - This paper considers how the full range of human experience may catalyze a
      placebo response. The placebo effect has been characterized as something to
      control in clinical research, something to cultivate in clinical practice and
      something present in all healing encounters. We examine domains in which the term
      'placebo' is used in discourse: clinical research, clinical practice, media
      representations of treatment efficacy and lay interpretations of placebo--an
      underresearched topic. We briefly review major theoretical frameworks proposed to
      explain the placebo effect: classical conditioning, expectancy, the therapeutic
      relationship and sociocultural 'meaning.' As a corrective to what we see as an
      overemphasis on conscious cognitive approaches to understanding placebo, we
      reorient the discussion to argue that direct embodied experience may take
      precedence over meaning-making in the healing encounter. As an example, we
      examine the neurobiology of rehearsing or visualizing wellness as a mode of
      directly (performatively) producing an outcome often dismissed as a 'placebo
      response.' Given body/mind/emotional resonance, we suggest that the placebo
      response is an evolutionarily adaptive trait and part of healing mechanisms
      operating across many levels--from genetic and cellular to social and cultural.

PMID- 19107584
TI  - The liver, the brain and nitrogen metabolism.

PMID- 19107586
TI  - Studies on Syntaxin 12 and alcohol preference involving C57BL/6J and DBA/2J
      strains of mice.
AB  - C57BL/6J and DBA/2J inbred mouse strains have been extensively studied for the
      genetic dissection of alcohol-related phenotypes. We have previously found
      Syntaxin 12 to be associated with alcohol preference in C57BL/6J and DBA/2J due
      to its strain-specific and ethanol responsive expression in the male brain. In
      the current study, we combined genetic and expression analyses to assess the
      segregation of Syntaxin 12 c.*1370G>A polymorphism with its strain-specific
      expression and alcohol preference in an F (2) population (N = 427) derived from
      C57BL/6J and DBA/2J strains. Syntaxin 12 c.*1370G>A polymorphism was found to
      segregate with alcohol preference in the B6D2F2 population and a correlation was
      identified between Syntaxin 12 expression and alcohol preference in the selected
      B6D2F2 males (r = -0.473, r (2) = 0.22). We followed up our analysis in the BXD
      RI lines using resources from WebQTL and the Mouse Phenome Database. Our study
      detected significant associations of Syntaxin 12 molecular variants with its
      level of expression and alcohol preference in B6D2F2 males. Overall, our findings
      support a role for Syntaxin 12 as a potential contributor to alcohol preference
      in mice.

PMID- 19107587
TI  - An analysis of electronically monitored adherence to antiretroviral medications.
AB  - Medication adherence studies increasingly collect data electronically, often
      using Medication Event Monitoring System (MEMS) caps. Analyses typically focus on
      summary adherence measures, although more complete analyses are possible using
      adaptive statistical methods. These methods were used to describe individual
      subject adherence patterns for MEMS data from a clinical trial. Subjects were
      adaptively clustered into groups with similar adherence patterns and clusters
      were compared on a variety of subject characteristics. There were seven different
      adherence clusters: consistently high, consistently moderately high, consistently
      moderate, consistently moderately low, consistently low, deteriorating starting
      early, and deteriorating late. Compared to other subjects, subjects with
      consistently high and consistently moderately high adherence were more likely to
      be male, White, and older and to maintain during study participation a CD4 cell
      count over 500 and an HIV viral load of at most 400 copies/ml. These results
      demonstrate the effectiveness of adaptive methods for comprehensive analysis of
      MEMS data.

PMID- 19107588
TI  - The triumph of pharmaceuticals: the portrayal of depression from 1980 to 2005.
AB  - This paper reports on a study of the media portrayal of depression in all of the
      98 articles recovered from high circulating magazines directed towards diverse
      audiences in Canada and the US from 1980 to 2005. Through qualitative analysis of
      manifest and latent messages the paper compares stories from the 1980s with those
      from the 1990s and 2000s with respect to how they answer the following questions
      about depression: What is it? Where is it? Who gets it? What can or should be
      done about it? It also looks at the use of metaphors, the deployment of
      celebrities as representatives of depression and the links made with physical
      illness. The answers to all questions document a trend over time towards a
      reductionistic and bio-medicalized notion of depression. Depression moved from a
      problem explained in a variety of ways in the 1980s to a primarily bio-medical
      phenomenon in mass magazines in the 1990s and 2000s. Theoretical explanations and
      practical consequences at the individual, therapeutic and societal levels are
      considered.

PMID- 19107589
TI  - Caspase-3 and VEGF immunopositivity in seminiferous tubule germ cells in cases of
      obstructive and non-obstructive azoospermia in smokers versus non-smokers.
AB  - PURPOSE: To investigate immunostaining pattern of caspase-3, an apoptosis marker,
      and vascular endothelial growth factor (VEGF), an hypoxia marker in testis biopsy
      specimens collected either from smoking or non-smoking patients with azoospermia.
      METHODS: Testis biopsy specimens were obtained from thirty seven non-smoker and
      thirty eight smoker patients. Using immunochemistry technique, caspase-3 and VEGF
      were evaluated in all intratubular spermatogenic and interstitial Leydig cells.
      RESULT(S): Caspase-3 expression was significantly increased in germ cells in
      maturation arrest specimens in smoker azoospermic patients. No statistically
      significant difference was present between smokers and non-smokers for caspase-3
      expression in Sertoli cell. However, the VEGF immunopositive Leydig cells were
      statistically higher in smokers. There were no differences between groups in
      terms of germ cell immunopositivity. CONCLUSION: Our results support the
      hypothesis that increased apoptosis contributes significantly to impaired
      spermatogenesis. We conjecture that germ cell apoptosis may be augmented by
      hypoxic microenvironments and environmental toxicants in smoking azoospermic men.

PMID- 19107590
TI  - Effect of powdered gloves, worn at the time of embryo transfer, on the pregnancy
      outcome of IVF cycles.
AB  - PURPOSE: To assess the effect of wearing powdered gloves during embryo transfer
      as compared to un-powdered gloves on the pregnancy outcome of IVF cycles.
      METHODS: Patients, undergoing embryo transfer procedures, were prospectively
      randomized into two groups: In the first (group A, n=356) group embryo transfer
      was performed while wearing powdered gloves; in the second (group B, n=356) group
      embryo transfer was performed while wearing un-powdered gloves. The primary end
      point of the study was the clinical pregnancy rate. RESULTS: The two groups were
      comparable with respect to the mean age, mean number of grade one embryos
      obtained, and the mean number of embryos transferred. The clinical pregnancy
      rates of the two groups were not different. CONCLUSIONS: Powdered gloves, worn
      during embryo transfer, have no adverse effect on the pregnancy outcome of IVF
      cycles.

PMID- 19107592
TI  - Temperament and risk for depressive symptoms in adolescence: mediation by
      rumination and moderation by effortful control.
AB  - The present study examined the relations between temperament, ruminative response
      style and depressive symptoms both cross-sectionally and prospectively (1 year
      follow-up) in a community sample of 304 seventh- through tenth-graders. First,
      higher levels of negative affectivity (NA), lower levels of positive affectivity
      (PA) and lower levels of effortful control (EC) were found to be associated with
      higher levels of depressive symptoms. Second, the association between NA and PA
      on the one hand and depressive symptoms on the other was significantly moderated
      by level of EC (low PA and high NA are associated with depressive symptoms only
      if EC is low) and these relations were moderated by sex in the cross-sectional
      data. In the prospective data, T1 depressive symptoms and PA predicted T2
      depressive symptoms; with EC approaching significance. Third, rumination also
      predicted T1 as well as T2 depressive symptoms. Finally, support was found for a
      model of moderated mediation: higher levels of NA were associated with higher
      levels of ruminative response style, which was in turn related to more depressive
      symptoms but only in individuals with low EC and this was true for the cross
      sectional as well as the prospective data albeit with noteworthy differences in
      pattern. These findings confirm and extend previous findings on the associations
      between temperament, response styles and depression in adolescence and, as such,
      add to the growing body of research providing support for the applicability of
      cognitive vulnerability theories to depression in younger populations.

PMID- 19107591
TI  - Social information processing in elementary-school aged children with ADHD:
      medication effects and comparisons with typical children.
AB  - Examined social information processing (SIP) in medicated and unmedicated
      children with ADHD and in controls. Participants were 75 children (56 boys, 19
      girls) aged 6-12 years, including 41 children with ADHD and 34 controls. Children
      were randomized into medication conditions such that 20 children with ADHD
      participated after receiving placebo and 21 participated after receiving
      methylphenidate (MPH). Children were shown scenarios depicting peer interactions
      and asked to interpret each scenario and to generate possible responses to the
      scenario. Results showed that children with ADHD who received MPH generated more
      hostile responses to provocation than controls, but children with ADHD on placebo
      did not. Results also showed that children with ADHD regardless of medication
      generated more hostile responses to provocation than to peer entry, whereas
      controls did not. Findings suggest that children with ADHD generate more
      aggressive responses to provocation than controls and that this may be
      exacerbated by administration of MPH. Limitations and future directions are
      discussed.

PMID- 19107593
TI  - Cyclin E deregulation is an early event in the development of breast cancer.
AB  - Cyclin E has been shown to be overexpressed in some human breast cancers,
      however, data to support deregulation of cyclin E as an early event in human
      mammary tumor development is lacking. We analyzed surgical specimens from 183
      patients with breast carcinomas and evaluated cyclin E expression in areas of
      invasive carcinoma, adjacent carcinoma in situ (CIS), and non-neoplastic breast
      parenchyma. Overexpression of cyclin E was seen in one-third of invasive
      carcinoma samples, one-third of the CIS component and nearly half of the non
      neoplastic breast epithelial cells adjacent to carcinoma (44% vs. 33%, P < or =
      0.05). Nuclear labeling for cyclin E was highly concordant between areas of in
      invasive carcinoma, CIS and non-neoplastic breast epithelial cells from the same
      patient (P < 0.0001). Localization of cyclin E to the cytoplasm was seen in a
      small proportion of tumor samples. Our findings suggest that cyclin E
      deregulation is an early event in the progression from histologically benign
      mammary epithelial cells to invasive carcinoma and occurs through both
      overexpression and altered cellular localization.

PMID- 19107594
TI  - The variance of length of stay and the optimal DRG outlier payments.
AB  - Prospective payment schemes in health care often include supply-side insurance
      for cost outliers. In hospital reimbursement, prospective payments for patient
      discharges, based on their classification into diagnosis related group (DRGs),
      are complemented by outlier payments for long stay patients. The outlier scheme
      fixes the length of stay (LOS) threshold, constraining the profit risk of the
      hospitals. In most DRG systems, this threshold increases with the standard
      deviation of the LOS distribution. The present paper addresses the adequacy of
      this DRG outlier threshold rule for risk-averse hospitals with preferences
      depending on the expected value and the variance of profits. It first shows that
      the optimal threshold solves the hospital's tradeoff between higher profit risk
      and lower premium loading payments. It then demonstrates for normally distributed
      truncated LOS that the optimal outlier threshold indeed decreases with an
      increase in the standard deviation.

PMID- 19107595
TI  - Cardiomyocyte-specific inactivation of thyroid hormone in pathologic ventricular
      hypertrophy: an adaptative response or part of the problem?
AB  - Recent studies in various rodent models of pathologic ventricular hypertrophy
      report the re-expression of deiodinase type 3 (D3) in cardiomyocytes. D3
      inactivates thyroid hormone (T3) and is mainly expressed in tissues during
      development. The stimulation of D3 activity in ventricular hypertrophy and
      subsequent heart failure is associated with severe impairment of cardiac T3
      signaling. Hypoxia-induced signaling appears to drive D3 expression in the
      hypertrophic cardiomyocyte, but other signaling cascades implicated in
      hypertrophy are also capable of stimulating transcription of the DIO3 gene. Many
      cardiac genes are transcriptionally regulated by T3 and impairment of T3
      signaling will not only reduce energy turnover, but also lead to changes in gene
      expression that contribute to contractile dysfunction in pathologic remodeling.
      Whether stimulation of D3 activity and the ensuing local T3-deficiency is an
      adaptive response of the stressed heart or part of the pathologic signaling
      network leading to heart failure, remains to be established.

PMID- 19107596
TI  - Meta-analysis of randomized and controlled treatment trials for achalasia.
AB  - Pharmacological therapy, botulinum toxin injection, pneumatic dilatation, and
      surgical myotomy are the primary therapeutic modalities for achalasia, for which
      laparoscopic myotomy is recommended as state-of-the-art therapy. However, its
      efficacy and safety remain unclear compared with other approaches in the
      treatment of achalasia. We searched electronic databases (MEDLINE, EMBASE,
      Cochrane Central Registry of Controlled Trials, LILACS-Latin American, Caribbean
      health science literature, and Science Citation Index Expanded) for randomized
      controlled trials to evaluate which therapeutic measures are temporary and
      reversible and which measures are definitive and effective by pooling data
      including remission rate, relapse rate, complications, and adverse effects.
      Seventeen studies with 761 patients met our inclusion criteria. There was better
      remission rate in pneumatic dilation than in botulinum toxin injection for
      initial intervention [relative risk (RR) 2.20, 95% confidence interval (CI) 1.51
      3.20], Pneumatic dilation had lower relapse rate than did botulinum toxin
      injection (RR 0.12, 95% CI 0.04-0.32). Compared with pneumatic dilation,
      laparoscopic myotomy further increased remission rate (RR 1.48, 95% CI 1.48
      1.87), and reduced clinical relapse rate (RR 0.14, 95% CI 0.04-0.58), and there
      was no difference in complication rate (RR 1.48, 95% CI 0.37-5.99). Based on
      limited randomized and controlled trials, laparoscopic myotomy is the preferred
      method for patients with achalasia. Future trials should investigate whether
      laparoscopic myotomy combined with different modalities of fundoplication is
      superior to isolated laparoscopic myotomy.

PMID- 19107597
TI  - Evidence of mechanical load redistribution at the knee joint in the elderly when
      ascending stairs and ramps.
AB  - This study examined the external joint moments at the lower extremity in all
      three directions in a group of older and younger adults when ascending stairs and
      ramps. Twenty-eight older and 16 younger adults ascended a purpose-built
      staircase and ramp. A motion capture system and a force plate were used to
      determine the subjects' 3D kinematics and ground reaction forces. Calculation of
      the leg kinematics and kinetics was done by means of a rigid, three-segment, 3D
      leg model. Older had lower dorsiflexion and knee flexion moments but higher hip
      flexion moments than the younger adults, independent of locomotion condition.
      Concerning the other two planes, older adults showed higher adduction moments at
      the knee and hip joint, and higher knee internal rotation moments. Furthermore,
      the elderly showed a more external position of the shank in relation to the thigh
      at the initiation of the stance phase for the two conditions examined. The higher
      adduction and internal rotation moments at the knee when combined with the
      kinematic changes in the transverse plane for the elderly give evidence that
      older adults redistribute the mechanical load within the load bearing regions of
      the knee. We concluded that the redistribution in knee joint loading may increase
      the risk factors for developing knee osteoarthritis in the elderly.

PMID- 19107598
TI  - Volume ordering for analysis and modeling of vascular systems.
AB  - Morphological characteristics of vascular systems are commonly presented in terms
      of Strahler order because the logarithms of quantities such as vessel diameter
      and length are often linearly related to Strahler order. However, the ability to
      interpret Strahler order geometrically or physiologically is compromised because
      the precision of the order number is limited to integer values. This limitation
      is overcome by the volume ordering scheme, in which volume order number is
      defined as the logarithm of the estimated perfused tissue volume for each
      vascular segment. While Strahler and volume order numbers are equivalent for
      completely symmetrical branching trees, they deviate in the presence of
      asymmetries. The physiology-based definition of volume ordering offers benefits
      in the analysis of vascular design, fractal characterization of vascular systems,
      and blood flow modeling. These benefits are illustrated based on arterial kidney
      data that show a linear relationship of logarithmic vessel diameter and
      conductance as a function of both Strahler order and volume order with differing
      proportionality constants, which are expected to depend on the branching
      characteristics of the particular organ investigated.

PMID- 19107600
TI  - The use of verb information in parsing: different statistical analyses lead to
      contradictory conclusions.
AB  - The research investigated how comprehenders use verb information during syntactic
      parsing. Two reading experiments investigated the relationship between verb
      specific variables and reading time. These experiments were close replications of
      prior work; however, two statistical techniques were used, rather than one. These
      were item-by-item correlations and participant-by-participant regression. In
      Experiment 1, reading time was measured using a self-paced moving window. In
      Experiment 2, eye movements were recorded during reading. The results of both
      experiments showed that the results of two types of statistical analyses support
      contradictory conclusions. The analyses involving participant-by-participant
      regression analyses provided no evidence for the early use of verb information in
      parsing and support syntax-first approaches to parsing. In contrast, the results
      of item-by-item correlation were consistent with the prior research, supporting
      the view that verb information can guide initial parsing decisions. Implications
      for theories of parsing are discussed.

PMID- 19107599
TI  - Nonlinear osmotic properties of the cell nucleus.
AB  - In the absence of active volume regulation processes, cell volume is inversely
      proportional to osmolarity, as predicted by the Boyle Van't Hoff relation. In
      this study, we tested the hypothesis that nuclear volume has a similar
      relationship with extracellular osmolarity in articular chondrocytes, cells that
      are exposed to changes in the osmotic environment in vivo. Furthermore, we
      explored the mechanism of the relationships between osmolarity and nuclear size
      and shape. Nuclear size was quantified using two independent techniques, confocal
      laser scanning microscopy and angle-resolved low coherence interferometry.
      Nuclear volume was osmotically sensitive but this relationship was not linear,
      showing a decline in the osmotic sensitivity in the hypo-osmotic range. Nuclear
      shape was also influenced by extracellular osmolarity, becoming smoother as the
      osmolarity decreased. The osmotically induced changes in nuclear size paralleled
      the changes in nuclear shape, suggesting that shape and volume are
      interdependent. The osmotic sensitivity of shape and volume persisted after
      disruption of the actin cytoskeleton. Isolated nuclei contracted in response to
      physiologic changes in macromolecule concentration but not in response to
      physiologic changes in ion concentration, suggesting solute size has an important
      influence on the osmotic pressurization of the nucleus. This finding in turn
      implies that the diffusion barrier that causes osmotic effects is not a semi
      permeable membrane, but rather due to size constraints that prevent large solute
      molecules from entering small spaces in the nucleus. As nuclear morphology has
      been associated previously with cell phenotype, these findings may provide new
      insight into the role of mechanical and osmotic signals in regulating cell
      physiology.

PMID- 19107601
TI  - A web-based survey of the relationship between buddhist religious practices,
      health, and psychological characteristics: research methods and preliminary
      results.
AB  - A Web-based survey was conducted to study the religious and health practices,
      medical history and psychological characteristics among Buddhist practitioners.
      This report describes the development, advertisement, administration and
      preliminary results of the survey. Over 1200 Buddhist practitioners responded.
      Electronic advertisements were the most effective means of recruiting
      participants. Survey participants were mostly well educated with high incomes and
      white. Participants engaged in Buddhist practices such as meditation, attending
      meetings and obtaining instruction from a monk or nun, and practiced healthful
      behaviors such as regular physical activity and not smoking. Buddhist meditative
      practice was related to psychological mindfulness and general health.

PMID- 19107602
TI  - Expression of COX-2 in stomach carcinogenesis.
AB  - BACKGROUND: Gastric cancer is a frequent cause of cancer in Brazil. The
      understanding of gastric carcinogenesis is not completely known but the progress
      of the molecular biology has provided that the initiation and progression of
      gastric cancer process is a consequence of a cumulative series of multiple gene
      alterations. AIM: The aim of the study is to investigate the relationship among
      cytoplasmatic COX-1 and COX-2, Bcl-2 and nuclear P53 in chronic gastritis,
      metaplasia, and intestinal and gastric cancer. PATIENTS AND METHODS: COX-1, COX
      2, P53, and Bcl-2 were evaluated by immunohistochemistry in 34 gastric
      adenocarcinoma (GA) tissues obtained from gastric resection, 21 tissues of
      patients with chronic gastritis (CG), and 34 with intestinal metaplasia (IM)
      obtained from endoscopic biopsies. RESULTS: COX-1 and COX-2 were expressed in
      more than 85% of the tissues. A correlation between COX-1 and COX-2 were observed
      (r = 0.66). P53 was positive in 29% CG, 20% of IM and in 59 % of GA. Bcl-2 was
      negative in all the CG, in 88% of IM, and in 85% of GA. P53 staining was
      expressed more frequently in gastric cancer when compared to CG (p = 0.05) or IM
      (p = 0.003). The expression of Bcl-2 was also higher in gastric cancer (p =
      0.002) and in intestinal metaplasia (p = 0.04) when compared to CG. There were no
      difference between metaplasia and chronic gastritis for P53 or Bcl-2. The
      immunoreactivity of COX-2 in gastric cancer was higher in the intestinal type
      (58%) than in diffuse type. A higher expression of COX-2 was found in advanced
      gastric cancer (p = 0.019). P53 was also more frequent in node positive cancer (p
      = 0.04). CONCLUSION: COX-2 is probably involved in gastric carcinogenesis, being
      an early alteration in cancer. Although we observed in this study a correlation
      between COX-2 and depth of cancer, this association as a prognostic marker is not
      well defined. P53 and Bcl-2 was expressed mainly in gastric cancer, being
      probably a latest alteration in gastric development.

PMID- 19107603
TI  - c-Jun N-terminal kinases inhibitor suppresses the TNF-alpha induced MCP-1
      expression in human umbilical vein endothelial cells.
AB  - Monocyte chemoattractant protein-1 (MCP-1) is a 76-amino-acid chemokine that is
      considered to be an important chemotactic factor for monocytes. MCP-1 is
      expressed in the macrophage-rich areas of atherosclerotic lesions. A recent
      report indicated that MCP-1 expression in human umbilical vein endothelial cells
      (HUVECs) is induced by the stimulation of tumor necrosis factor (TNF)-alpha via
      the c-Jun N-terminal kinases (JNK) pathway. In this study, we examined the
      effects of JNK inhibitor (JNKI-1), on MCP-1 expression. The results of this study
      indicated that the expression of MCP-1 mRNA and protein were stimulated in the
      presence of TNF-alpha. TNF-alpha stimulated the phosphrylation of JNK, however,
      JNKI-1 inhibited the TNF-alpha stimulated MCP-1 secretion and gene expression. As
      expected, JNKI-1 blocked the stimulatory effect of TNF-alpha on the MCP-1
      promoter activity. In conclusion, JNKI-1 partially inhibits the TNF-alpha-induced
      MCP-1 expression in HUVECs, and therefore JNKI-1 may be of therapeutic value in
      the treatment of diseases such as atherosclerosis.

PMID- 19107604
TI  - Full-Length gene enrichment by using an optimized RNA isolation protocol in Bixa
      orellana recalcitrant tissues.
AB  - A reliable protocol is described for isolation of large full-length cDNA from
      Bixa orellana mature tissues containing large quantities of pigments, phenols,
      and polysaccharides. This protocol involves the optimization of a commercial RNA
      extraction protocol in combination with a long distance reverse transcript PCR
      protocol. The principal advantages of this protocol are its high RNA yield and
      quality. The resulting RNA is suitable for RNA expression evaluation and
      production of large, full-length cDNA. This is the first time RNA has been
      isolated from all mature tissues in the tropical perennial plant B. orellana and
      has been proved viable for downstream applications, especially important for
      molecular biology studies on this economically important pigment-producing plant.

PMID- 19107605
TI  - Gene cloning, expression, and characterization of the Geobacillus Thermoleovorans
      CCR11 thermoalkaliphilic lipase.
AB  - The gene for a Geobacillus thermoleovorans CCR11 thermostable lipase was
      recovered by PCR and cloned. Four genetic constructions were designed and
      successfully expressed in E. coli: (i) the lipase structural gene (lipCCR11) in
      the PinPoint Xa vector; (ii) the lipase structural gene (lipACCR11) in the pET
      28a(+) vector; (iii) the lipase structural gene minus the signal peptide
      (lipMatCCR11) in the pET-3b vector; and (iv) the lipase structural gene plus its
      own promoter (lipProCCR11) in the pGEM-T cloning vector. The lipase gene sequence
      analysis showed an open reading frame of 1,212 nucleotides coding for a mature
      lipase of 382 residues (40 kDa) plus a 22 residues signal peptide. Expression
      under T7 and T7lac promoter resulted in a 40- and 36-fold increase in lipolytic
      activity with respect to the original strain lipase. All recombinant lipases
      showed an optimal activity at pH 9.0, but variations were found in the
      temperature for maximum activity and the substrate specificity among them and
      when compared with the parental strain lipase, especially in the recombinant
      lipases that contained fusion tags. Therefore, it is important to find the
      appropriate expression system able to attain a high concentration of the
      recombinant lipase without compromising the proper folding of the protein.

PMID- 19107607
TI  - Tooth-forming potential in embryonic and postnatal tooth bud cells.
AB  - Humans are genetically programmed to replace their teeth once during childhood.
      Therefore, when adult teeth are lost or damaged, they cannot be regenerated or
      regrown. However, with the advancement of stem cell biology and tissue
      engineering, regenerating the whole tooth has become a realistic and attractive
      option to replace a lost or damaged tooth, and therefore has strongly attracted
      attention in the field of dental research. During the past several years,
      significant progress has been made in this research endeavor, providing greater
      understanding of the production of an entire biological tooth by tissue
      engineering using stem cells. There are several ways to reproduce an entire
      biological tooth. Approaches are categorized according to the cell sources that
      have the potential to produce teeth. One source is the embryonic tooth bud, and
      the other is the postnatal tooth bud. The results from embryonic and postnatal
      tooth buds differ considerably. In particular, the potential to regulate the
      shape of the tooth crown from embryonic tooth bud is higher than from postnatal
      tooth bud. This article describes the achievements to date in production of
      biological teeth, mostly from our laboratory. In particular, we describe the
      potential to produce teeth from embryonic and postnatal tooth buds.

PMID- 19107608
TI  - The primary cilia of secretory cells in the human oviduct mucosa.
AB  - The human oviduct is lined with a simple columnar epithelium composed of ciliated
      cells and secretory cells. Primary cilia or solitary cilia usually extend from
      the apical surface of the secretory cells. The axoneme of the primary cilia is
      composed of nine peripheral microtubule doublets (9 + 0 pattern) that lack dynein
      arms and nexin links. Displacement of peripheral doublets to the central region,
      which is suggested to be attributable to the lack of nexin links, is one of the
      distinctive features of oviductal primary cilia. The basal body that extends the
      primary cilium connects to its paired centriole by the striated connector. The
      basal body is associated with the accessory structures, such as alar sheets,
      basal feet, and striated rootlets. Several basal feet project laterally from the
      basal body. The cap of the basal foot serves as the microtubule organizing
      center. Several striated rootlets radiate from the basal body toward the nucleus.
      The basal body, the paired centriole, and the basal body-associated structures
      are considered to play important roles in the stabilization and fixing of the
      cilium in the proper position on the apical cell surface.

PMID- 19107609
TI  - The Kras2 oncogene and mouse lung carcinogenesis.
AB  - Activating point mutations of the mouse Kras2 oncogene or its human homologue,
      KRAS, are critical for lung adenocarcinoma genesis, independent of the species.
      Significantly, in the mouse, several polymorphic Kras2 alleles have been
      identified, which cosegregate with genetic susceptibility to chemical induction
      of lung tumors. Moreover, a major lung tumor susceptibility locus, the Pas1
      (Pulmonary adenoma susceptibility 1), was found to colocalize with Kras2 on
      distal chromosome 6 on linkage analysis. The Kras2 may thus be involved in both
      cellular transformation and genetic control of tumor susceptibility. In this
      review, the focus is on current knowledge regarding the relationship between
      Kras2 and experimental mouse lung carcinogenesis, especially from the aspect of
      disease predisposition. Because mouse and human lung tumors share considerable
      similarities, the experimental information should provide clues to personalized
      medicine in the human setting.

PMID- 19107611
TI  - Sodium azide induces necrotic cell death in rat squamous cell carcinoma SCC131.
AB  - Sodium azide (NaN(3)) is widely used in industry and agriculture, and also in
      laboratories as a potent preservative. NaN(3) induces cell death when applied to
      cultured cells. However, whether the mode of cell death is apoptosis or necrosis
      remains a subject of debate. There have been no previous reports on NaN(3)
      induced cell death in squamous cell carcinoma (SCC), and so we studied the mode
      of cell death induced by NaN(3) using the rat SCC cell line, SCC131. In this
      experiment, SCC131 cells died 48-72 h after NaN(3) treatment with concentrations
      greater than 5 mM. The NaN(3) treatment reduced the mitochondrial membrane
      potential and ATP content. Terminal deoxynucleotidyl transferase-mediated dUTP
      nick-end labeling and DNA ladder detection assay indicated that no DNA
      fragmentation occurred. In addition, phosphatidyl serine did not appear on the
      cell surface, according to the findings of dye-uptake bioassay and flow
      cytometric analysis of Annexin V labeling. Electron microscopic analysis revealed
      that the NaN(3)-treated cells showed mitochondrial swelling and rupture of the
      cell membrane. In conclusion, NaN(3) induces necrotic cell death in SCC131. This
      experimental model may be used in the study of necrotic cell death.

PMID- 19107610
TI  - Ultrastructural study of the morphogenesis of human herpesvirus 6 type B in human
      T-lymphotropic virus type I-producing lymphoid cells.
AB  - A few studies of the morphogenesis of human herpesvirus (HHV) 6 type A and B (HHV
      6A, -6B) have been performed using neurogenic, lymphoid, or epithelial cells.
      When human MT-4 T-lymphotropic virus type I (HTLV-I)-producing lymphoid cells
      were coinfected with HHV-6B in vitro, viral-specific proteins were clearly
      detected. We therefore attempted to detect virus particles at the ultrastructural
      level, focusing on the morphogenesis of such particles. Ultrastructurally, HHV-6B
      virus particles could be observed in the nuclei, cytoplasm, and extracellular
      spaces of MT-4 cells, in addition to extracellular HTLV-I particles of C type. In
      the nuclei, dense-cored or doughnut-shaped viral capsids were found, as well as
      peculiar tubular rods. When budding to perinuclear spaces, these intranuclear
      capsids exhibited a thin tegument on their surfaces. Distinct teguments were
      found in the intracytoplasmic particles, which budded into cytoplasmic vacuoles
      during the process of maturation. The mature particles were detected in the
      extracellular spaces and the intracytoplasmic vacuoles, with a distinct tegument
      and surface spikes. An electron-dense layer in the outer part of the tegument was
      found in some mature particles located in the extracellular space, but no such
      layer was detected in mature particles in intracytoplasmic vacuoles. No annulate
      lamellae, but intranuclear tubular rods, were found in the cytoplasm of MT-4
      cells. These observations indicate that HHV-6B in MT-4 cells is similar to HHV-6A
      in fine structure, but differs from HHV-7 and HHV-8 in ultrastructural
      characteristics. Further comparisons of HHV-6B with HHV-6A, HHV-7, and HHV-8 are
      needed with regard to functional activity.

PMID- 19107612
TI  - Immunohistochemical and electron microscopic observations of stromal cells in the
      human oviduct mucosa.
AB  - Stromal cells in the lamina propria of the human oviduct mucosa are unique cells
      that can differentiate into decidual cells during ectopic pregnancy in the
      oviduct. The nature of stromal cells is still unknown. In the present study, we
      investigated human oviductal stromal cells with transmission electron microscopy
      and immunohistochemistry and revealed that they had ultrastructural features
      similar to myofibroblasts and expressed alpha-smooth muscle actin, a marker used
      to identify myofibroblasts. Primary cilia were also one of the characteristic
      profiles of the stromal cells. These findings showed that the connective tissue
      stromal cells in the human oviduct mucosa are myofibroblasts. They are considered
      to play an important role in the transport of oocytes by bringing about
      contraction of the mucosal folds.

PMID- 19107613
TI  - Chromophobe renal cell carcinoma: useful diagnostic application of imprint
      cytology and fluorescence in situ hybridization of chromosomes 10 and 21 in two
      cases of typical and eosinophilic variants.
AB  - Chromophobe renal cell carcinoma (RCC) is subdivided into typical and
      eosinophilic variants. We report such two cases with focus on imprint cytology
      and fluorescence in situ hybridization (FISH). The first case is a 53-year-old
      Japanese man and the second is a 76-year-old Japanese man. Histologically, the
      diagnosis of typical and eosinophilic variants of chromophobe RCC was suspected.
      In imprint cytology, irregularity of nuclear membrane, binucleation, perinuclear
      halo, and thick cell border were observed. Immunohistochemically, neoplastic
      cells of both tumors were positive for cytokeratin 7, E-cadherin, c-kit, and
      CD10. In FISH study, both tumors revealed the monosomy of chromosomes 10 and 21.
      Additionally, FISH study in eosinophilic variant of chromophobe RCC showed the
      disomy of chromosomes 7 and 17. In conclusion, we suggest that the combination
      study of imprint cytology and FISH of chromosomes 10 and 21 as well as routine
      histology may contribute to the accurate diagnosis of chromophobe RCC.

PMID- 19107614
TI  - An autopsy case of chronic progressive external ophthalmoplegia with renal
      insufficiency.
AB  - An autopsy of a 44-year-old Japanese woman with mitochondrial cytopathy confirmed
      the presence of chronic progressive external ophthalmoplegia (CPEO).
      Immunohistochemistry using antimitochondrial antibody was performed to observe
      the ultrastructure of the skeletal muscle and renal tissues. The patient was born
      of consanguineous parents, developed normally, and was of average intelligence.
      At 22 years of age, the patient noticed hearing loss, and subsequently, over
      time, developed a progressive generalized muscle weakness, which included
      limitation of eye movement and ptosis. At age 41, a muscle biopsy was performed
      using the modified Gomori trichrome method and demonstrated the presence of
      ragged red fibers. After the evaluation of her results in conjunction with her
      clinical course, she was diagnosed with CPEO. Renal insufficiency was discovered
      at age 30, and the patient died at the age of 44 of respiratory failure caused by
      respiratory muscle weakness and pneumonia. The autopsy revealed fiber size
      variation within the skeletal muscle, and an antimitochondrial antibody analysis
      demonstrated the accumulation of mitochondria between the bundles of myofibrils,
      as well as in subsarcolemmal locations. Ultrastructurally, abnormal mitochondria
      with disoriented cristae and paracrystalline inclusions were seen. Although no
      remarkable histological changes were noted in the kidneys, tubular epithelial
      cells exhibited accumulated abnormal mitochondria, similar to those seen in the
      skeletal muscle. Because mitochondrial diseases can affect other energy-dependent
      organs in addition to the skeletal muscle, immunohistochemical examinations
      employing an antimitochondrial antibody are useful for obtaining further
      ultrastructural observations that can assist in making a distinct diagnosis of
      this systemic disorder.

PMID- 19107615
TI  - Coexistent adenomyoepithelioma and invasive ductal carcinoma of the breast:
      presentation as separate tumors.
AB  - Adenomyoepitheliomas are rare breast tumors. We report an unusual case of
      adenomyoepithelioma associated with invasive ductal carcinoma here.
      Histologically, the lesion consisted of two separate tumors. One nodule
      corresponded to invasive ductal carcinoma consisting of tubular and trabecular
      arrangements of columnar or cuboidal neoplastic cells. The other tumor
      corresponded to adenomyoepithelioma consisting of an inner layer of neoplastic
      cells with basophilic cytoplasm and the outer layer of neoplastic cells with
      clear cytoplasm. Immunohistochemically, some myofibroblasts were observed in the
      stroma of both adenomyoepithelioma and invasive ductal carcinoma, but no CD34
      positive stromal cells were seen in the stroma of either lesion. The stromal
      reaction of adenomyoepithelioma resembles that of intraductal papilloma in the
      previous study. To the best of our knowledge, this is the first case of
      coexistent adenomyoepithelioma and invasive ductal carcinoma of the breast that
      were discovered as separate nodules. Clinicians and pathologists should be aware
      of such an association because they need to distinguish such a case from
      malignant neoplasms arising in adenomyoepithelioma. Additionally, our preliminary
      report suggests that the stromal response of adenomyoepithelioma may resemble
      that of intraductal papilloma.

PMID- 19107617
TI  - Report on the FIGO-SOGP Saving the Mothers and Newborn Health Project in
      Pakistan. An NFOG concern.

PMID- 19107618
TI  - Reasons of refusal and drop out in a follow up study involving primigravidae in
      Pakistan.
AB  - OBJECTIVE: To determine the reasons underlying the refusals to participate and
      drop outs from a follow up study involving primigravidae. DESIGN: A descriptive
      study. METHODS: Aga Khan University and Aga Khan Hospital for Women, Karachi,
      jointly initiated a nested case-control study on primigravidae for determining
      the predictability of preeclampsia using various biochemical markers in blood.
      The protocol-eligible study subjects were counseled along with their accompanying
      family members to participate in the study. All women recruited in this study
      were followed up throughout their pregnancy till delivery. RESULTS: One thousand
      six hundred and sixty-five primigravidae were identified as the potential study
      subjects. Out of which, 1,307 (78.5%) consented and 358 (21.5%) refused to
      participate in the study. The most common reason underlying the refusal was
      inability to get permission from the family members (n=84; 34.4%) followed by
      fear of prick (n=51; 20.9%). For 114 refusals, either the reason was not
      mentioned by the counseled women (n=60) or the data was missing (n=54). Out of
      1,307 women recruited in the research, only 611 (46.7%) women completed the study
      according to the prescribed protocol. Among the rest, 102 (7.8%) subsequently
      withdrew from the research, 503 (38.5%) were dropped out, and 91 (7.0%) were lost
      to follow up. CONCLUSIONS: Refusal to participate and drop out from the research
      program are two significant factors hindering the smooth flow of a study. In
      Pakistan, the major reason for the refusal by the protocol-eligible pregnant
      women for participating in a research program is the unwillingness of the family
      members.

PMID- 19107619
TI  - Early neonatal morbidity and mortality in growth-discordant twins.
AB  - OBJECTIVE: To evaluate early neonatal morbidity and mortality in twin pregnancies
      with growth discordance. DESIGN: Retrospective study. SETTING: Tertiary teaching
      hospital, Sao Paulo, Brazil. POPULATION: A total of 151 twin pregnancies managed
      and delivered at the Multiple Pregnancy Unit at Sao Paulo University Hospital
      between 1998 and 2004. METHODS; Comparison between twin pregnancies with weight
      discordance > or =20% and pregnancies concordant for fetal weight. Cases with
      fetal death, abnormalities, twin-to-twin transfusion and delivery before 26 weeks
      or in another hospital were excluded. OUTCOME MEASURES: Early neonatal morbidity
      (Apgar at 5 minutes <7, respiratory or neurological complications, infection,
      necrotizing enterocolitis, length of hospital stay) and mortality. RESULTS: Forty
      (26.5%) pregnancies presented discordance > or =20% and 111 (73.5%) were
      concordant. In the discordant group, 75% of pregnancies had at least one growth
      restricted fetus (<10th centile). In concordant twin pregnancies, monochorionic
      cases (22.5%) presented with lower gestational age (34.3 vs. 36.2 weeks), lower
      birthweight (2,067 vs. 2,334 g) and a longer period of hospital stay (5.5 vs.
      3.0) compared to dichorionic concordant twins. No differences between
      monochorionic and dichorionic subgroups were observed in discordant twins.
      Pregnancies in which at least one baby was born with a birthweight below the 10th
      centile showed that discordant pregnancies had a lower gestational age at
      delivery (35.2 vs. 36.8 weeks) and a longer period of hospital stay (9 vs. 4
      weeks) compared to concordant cases. Neonatal mortality was similar in discordant
      (3.7%) and concordant (4.5%) twins. CONCLUSION: Early perinatal morbidity is
      increased in twin pregnancies with birthweight discordance > or =20% only when
      associated with fetal growth restriction and low birthweight.

PMID- 19107620
TI  - Comparison of predicted and clinical response to radiotherapy: a radiobiology
      modelling study.
AB  - INTRODUCTION: A model to predict clinical outcome after radiation therapy would
      be a valuable aid in the effort of developing more tailored treatment regimes for
      different patients. In this work we evaluate the clinical utility of a model that
      incorporates the following individually measured radiobiology parameters:
      intrinsic radiosensitivity, proliferation and number of clonogenic cells. The
      hypothesis underlying the study was that the incorporation of individually
      measured tumour parameters in a model would increase its reliability in
      predicting treatment outcome compared with the use of average population derived
      data. MATERIAL AND METHODS: Forty-six patients with head and neck tumours were
      analyzed, the majority of whom received both external beam radiotherapy and
      brachytherapy. Eighteen patients received external beam treatment alone and
      statistical analyses were carried out on this subgroup. RESULTS: Four of the 18
      patients had a >95% calculated probability of cure and none developed a local
      recurrence resulting in a negative predictive value of 100% (compared with 67%
      for population-derived data). The sensitivity of the model in predicting local
      recurrence was 75% (compared with 38% for population-derived data). Using a model
      that incorporated individually measured radiobiology data, there was a
      statistically significant difference in local control levels for patients with
      >95% and <5% predicted probability of local control (chi(2), p = 0.04).
      DISCUSSION: This study suggests, therefore, that incorporation of measured
      biological data within a radiobiological model improves its ability to predict
      radiation therapy outcome compared with the use of population-derived data.

PMID- 19107621
TI  - Co-expression of estrogen receptor alpha and Apolipoprotein D in node positive
      operable breast cancer--possible relevance for survival and effects of adjuvant
      tamoxifen in postmenopausal patients.
AB  - BACKGROUND: Estrogen receptor-alpha (ERalpha) is an important prognostic and
      predictive marker in breast cancer. ERalpha signaling normally down-regulates
      expression of Apolipoprotein D (ApoD), a lipocalin that binds, transports or
      chelates lipophilic ligands, including tamoxifen (TAM). Hence, the co-expression
      of ApoD may therefore identify clinical relevant subgroups of ERalpha positive
      breast cancer patients. MATERIAL AND METHODS: ApoD, ERalpha, and progesterone
      receptor (PR) protein expressions were determined by immunohistochemistry (IHC)
      in primary tumors of 290 patients with operable breast cancer. The median follow
      up was 12 years. Patients were stratified according to age, nodal stage and the
      expression of ERalpha and the combined cytoplasm and nuclear staining of ApoD
      (ApoD(CN)). RESULTS: In elderly women (> or =70 years) (n = 76), ApoD(CN)
      expression identified different prognostic subgroups in ERalpha positive patients
      (Trend: p < 0.0001). Multivariate analysis in this age group (n = 72), showed
      that the ERalpha-positive /ApoD(CN)-negative subgroup had a better breast cancer
      specific survival (BCSS) compared with the ERalpha-positive/ApoD(CN)-positive
      group (hazard ratio (HR) = 4.3; 95% CI = 1.6-11.9; p = 0.005). This difference
      was predominantly seen in the node positive patients (n = 30) (HR = 10.5; 95% CI
      = 2.3-47.6; p = 0.002). In a subset of postmenopausal ERalpha-positive/node
      positive patients (n = 60) previously enrolled in a trial on 2 year adjuvant TAM
      20 mg vs. placebo, a better BCSS was observed in ApoD(CN) negative patients
      compared to placebo (p = 0.02). In ApoD(CN) positive patients, adjuvant TAM did
      not provide any survival benefit. DISCUSSION: ERalpha and ApoD(CN) co-expression
      seems to be of prognostic importance in node positive elderly patients with
      operable breast cancer. In addition, we hypothesize that ApoD(CN) expression may
      be a novel marker and/or mechanism of TAM resistance in postmenopausal node
      positive patients. Thus, when targeting the ERalpha pathway in these patients,
      the ApoD status of the tumor may be of clinical relevance.

PMID- 19107622
TI  - Flare-up: an often unreported phenomenon nevertheless familiar to oncologists
      prescribing tyrosine kinase inhibitors.

PMID- 19107625
TI  - Chlorella powder inhibits the activities of peptidase cathepsin S, PLA2,
      cyclooxygenase-2, thromboxane synthase, tyrosine phosphatases, tumor necrosis
      factor-alpha converting enzyme, calpain and kinases.
AB  - A Chlorella powder was tested in 118 in vitro enzyme assay systems. The powder
      showed potent inhibitions of peptidase cathepsin S, thromboxane A(2) synthase and
      cyclooxygenase-2 in a dose-concentration manner with IC(50)+/-standard error of
      the mean values of 3.46+/-0.93 microg/ml, 3.23+/-0.69 microg/ml, and 44.26+/-9.98
      microg/ml, respectively. Other activities observed were inhibitions of tumor
      necrosis factor-alpha converting enzyme, protein tyrosine phosphatase (SHP-2),
      calpain, protein kinases and protein tyrosine phosphatases. Chlorella powder had
      no significant effect on cyclooxygenase-1. These actions to inhibit
      cyclooxygenase-2 and thromboxane synthase could contribute to the purported anti
      inflammatory and anti-thrombotic effects of Chlorella. These results reveal
      important potential biochemical activities to be developed that, if confirmed by
      in vivo studies, might be exploited for the prevention or treatment of several
      serious pathologies, including inflammatory diseases, immune and cancer.

PMID- 19107624
TI  - From bacteria to humans, chromatin to elongation, and activation to repression:
      The expanding roles of noncoding RNAs in regulating transcription.
AB  - Noncoding RNAs (ncRNAs) have emerged as key regulators of transcription, often
      functioning as trans-acting factors akin to prototypical protein transcriptional
      regulators. Inside cells, ncRNAs are now known to control transcription of single
      genes as well as entire transcriptional programs in response to developmental and
      environmental cues. In doing so, they target nearly all levels of the
      transcription process from regulating chromatin structure through controlling
      transcript elongation. Moreover, trans-acting ncRNA transcriptional regulators
      have been found in organisms as diverse as bacteria and humans. With the recent
      discovery that much of the DNA in genomes is transcribed into ncRNAs with yet
      unknown function, it is likely that future studies will reveal many more ncRNA
      regulators of transcription.

PMID- 19107627
TI  - Intake of some minerals in healthy adult volunteers from eastern Croatia.
AB  - Although minerals have important protective effects in human health, their role
      in nutrition is still underestimated and insufficiently investigated in Croatian
      population. The aim of this research was to examine sodium, potassium, magnesium,
      phosphorus, iron and copper intake in 120 adults, aged 18-54 years. The research
      was conducted using the 10 times repeated 24-h recall method during 1 year.
      Participants were separated according to age, as well as according to the sex and
      body mass index. There were significant differences in daily intake of sodium,
      potassium, magnesium and copper between age groups, but not for phosphorus and
      iron. When divided by sex, significant differences in daily intake were found for
      all minerals. When nutritive density was considered, significant difference was
      found only for potassium and magnesium regarding sex. In conclusion, considering
      recommendations, the sodium dietary intake of the examined population is too
      high, while the intake of iron is to low among women.

PMID- 19107626
TI  - Effects of polydextrose supplementation on different faecal parameters in healthy
      volunteers.
AB  - The beneficial effects of prebiotics on bowel health were thoroughly
      investigated. The aim of the study was to show prebiotic effects of polydextrose
      (PDX). A placebo-controlled, randomized intervention study with PDX
      supplementation (8 g/day) was conducted in 45 healthy subjects. The effects of
      PDX on stool weight, orofaecal transit time, consistency of stool (Bristol stool
      form scale), short-chain fatty acid production, pH value, neutral sterol and bile
      acid excretion and faecal microbiota were evaluated. It was found that
      supplementation of PDX shortened the orofaecal transit time significantly.
      Furthermore, ingestion of PDX resulted in a decreased pH value and in significant
      changes in bile acid and neutral sterol excretion. PDX had no effects on stool
      weight, concentrations of the main short-chain fatty acids (acetate, propionate)
      and faecal contents of lactic acid bacteria and bifidobacteria. In conclusion,
      PDX is able to shorten the orofaecal transit time and to improve stool
      consistency in subjects suffering from constipation. [corrected]

PMID- 19107628
TI  - Nutritional value of traditional Italian meat-based dishes: influence of cooking
      methods and recipe formulation.
AB  - The present study provides a picture of the compositional figure and nutritive
      value of meat-based dishes typical of Italian culinary tradition. Recipes
      specific for a bovine meat cut (top-side) were selected among the most widespread
      ones in Italy: in pan, pizzaiola, cutlet, meat ball, and escalope. The total fat
      and cholesterol content varied depending on the ingredients utilized (extra
      virgin olive oil, parmesan, egg). Meat-based dishes that utilized extra-virgin
      olive oil showed a significant reduction in palmitic and stearic acids and a
      parallel increase in oleic acid compared with raw meat; furthermore, the ratio
      among saturated fatty acids, monounsaturated fatty acids and polyunsaturated
      fatty acids shifted in favour of monounsaturated fatty acids. B vitamins were
      affected at different extent by heating; by contrast, vitamin E content increased
      because of the new sources of this vitamin, which masked losses due to heating.
      Ingredients (parmesan, discretionary salt) induced significant increases in the
      calcium and sodium concentrations compared with raw meat. The total iron content
      did not show marked differences in most of the meat-based dishes compared with
      raw meat; by contrast, losses in the heme-iron concentration were detected
      depending on the severity of heating treatments. Our findings suggest that heme
      iron, because of its important health aspects, might be a useful index of the
      nutritional quality of cooked meats.

PMID- 19107629
TI  - Transplantation of autologous minigrafts for the treatment of large-area
      segmental vitiligo.

PMID- 19107630
TI  - Structural brain mutants: mushroom body defect (mud): a case study.
AB  - Single-gene mutants of Drosophila have not only increased our understanding of
      the biochemical processes underlying learning and memory processes, but also
      established structure-function relationships. The first relevant mutants were
      identified by Martin Heisenberg nearly 30 years ago in a screen for altered adult
      brain structure and were used to link the mushroom bodies in the central brain
      with olfactory learning and memory processes. Because the observed structural
      defects in the adult are the consequence of deregulated developmental processes,
      the characterization of these mutants can also provide insight into the genetic
      programs underlying the establishment, maintenance, and remodeling of functional
      neuronal circuits. As an example for the value of this approach, we trace the
      history of mushroom body defect (mud), from the original anatomical description
      of the mutation to most recent insights of the function of the protein as a
      regulator of neuronal progenitor cell division.

PMID- 19107631
TI  - The genetic basis of emotional behavior: has the time come for a Drosophila
      model?
AB  - The aim of this review was to summarize the studies potentially relevant to
      whether Drosophila can be used as a genetically tractable model to study the
      genetic and molecular basis of emotional behavior. Can these studies contribute
      to a better understanding of neural substrates of abnormal emotional states and
      specific neuropsychiatric illnesses, such as depression and anxiety?

PMID- 19107632
TI  - Heisenberg's roadmap guides our journey to the small cognitive world of
      Drosophila.
AB  - Professor Martin Heisenberg is one of the pioneers in the exploration of
      neuroethology. With his inspiration and earnest help, we employed the fruitfly as
      a model system to investigate the underlying neural mechanism of cognitive
      behaviors. Here, we recalled the help from Martin in the early years and
      introduced some findings from our lab about visual cognition behaviors in
      Drosophila, such as decision making, selective attention, and experience
      dependent visual pattern recognition. From the results so far, the circuit
      composed of mushroom bodies, central complex, and dopaminergic neurons may play
      an essential role in these behaviors.

PMID- 19107633
TI  - The importance of being active.
AB  - The successful stimulus-response approach to the organization of behavior has
      been the dominating paradigm for much of the psychology and neuroscience of the
      20th century. Martin Heisenberg is a pioneer in championing the idea that all
      brains, even comparatively simple ones such as those of insects, instead operate
      according to output-input principles. Since the 1970s, his research produces
      evidence that the fruit fly, Drosophila melanogaster, is capable of spontaneous
      behavioral activity, and that the flies use it to control sensory input (i.e.,
      operant behavior). Today, more and more evidence is accumulating also from fields
      outside of neuroscience that, indeed, one of the common, defining principles of
      all brains is this concept of operant behavior. Drawing from this evidence, it
      becomes clear that the conceptually simple process of generating activity and
      evaluating its consequences forms one of the fundamental cornerstones not only
      for all of our human nature, but also for our social coherence. This review
      recapitulates Heisenberg's most critical experiments and provides an overview
      over the current literature on the role of spontaneous activity in the ecology
      and evolution of brains. I conclude that spontaneous activity is both a necessary
      prerequisite and an inevitable consequence of evolution.

PMID- 19107634
TI  - Exophiala asiatica, a new species from a fatal case in China.
AB  - We describe a new species, Exophiala asiatica, isolated from an infection of the
      pharynx in a 20-year-old, immunocompetent woman in Nanjing, China. The infection
      was initiated by a fishbone prick in the pharynx, soon developed with facial
      nodules but subsequently seemed to have disappeared. Tonsil ulceration with
      progressive soreness of the pharynx was observed 3 years later. Dysphagia,
      headache and paralysis occurred four years after first signs of infection. Hyphae
      and yeast-like cells were detected in tissue and a black fungus was recovered
      repeatedly from pharynx tissue. Despite antifungal therapy for more than one
      year, the patient died of apparent cerebral dissemination of the etiologic agent.
      On the basis of morphology, nutritional physiology, ribosomal small subunit DNA
      and ITS sequence data the strain could not be matched with any existing species.
      A new species, Exophiala asiatica, is therefore proposed.

PMID- 19107635
TI  - Genetic diversity and species delimitation in the opportunistic genus Fonsecaea.
AB  - Genetic diversity and species delimitation were investigated among 39 isolates
      recovered from clinical and environmental sources in Central and South America,
      Africa, East Asia and Europe. All had been morphologically identified as
      Fonsecaea spp. Molecular analyses were based on sequences of the ribosomal
      internal transcribed spacers (ITS), -tubulin (TUB1) and actin (ACT1) regions. A
      phylogenetic approach using haplotype networks was used to evaluate species
      delimitation and genetic diversity. The presence and the modes of reproductive
      isolation were tested by measuring the index of differentiation (ID) and the
      index of association (IA). Based on the sequence data, the 39 Fonsecaea strains
      were classified into three major entities: (i) a group representing Fonsecaea
      pedrosoi, (ii) a second composed of F. monophora, and (iii) a third group
      including mostly strains from South America. The two major, clinically relevant
      Fonsecaea species, F. monophora and F. pedrosoi, also differed in the
      pathological symptoms found in patients. Moreover, F. pedrosoi is mostly
      recovered in clinical settings, whereas F. monophora is commonly isolated from
      the environment. One environmental strain with Fonsecaea-like appearance was
      shown to belong to a different species, only distantly related to the core-group
      of Fonsecaea.

PMID- 19107636
TI  - Subcutaneous phaeohyphomycosis caused by Exophiala xenobiotica in a non-Hodgkin
      lymphoma patient.
AB  - Phaeohyphomycosis is a rare fungal infection that is more commonly associated
      with immunocompromised patients. We present a case in which a 77-year-old woman
      with non-Hodgkin lymphoma developed subcutaneous phaeohyphomycosis caused by
      Exophiala xenobiotica. E. xenobiotica is a dematiaceous hyphomycete that was
      recently identified as a segregant of the E. jeanselmei complex. The patient was
      successfully treated with local excision of the lesions and post-surgical oral
      itraconazole. The latter was administered with the aim of preventing systemic
      dissemination in this immunocompromised patient.

PMID- 19107637
TI  - Antifungal susceptibility testing of Exophiala spp.: a head-to-head comparison of
      amphotericin B, itraconazole, posaconazole and voriconazole.
AB  - Frequently, diseases caused by black yeasts are chronic in nature with a high
      morbidity. In addition, these infections are often fatal and relapse is common,
      even after prolonged treatment. Although the CLSI Document M38-A outlines methods
      for antifungal susceptibility testing of moulds, Exophiala spp. are not directly
      discussed. In an effort to determine the antifungal susceptibility patterns of
      Exophiala spp. we tested 160 clinical isolates against amphotericin B,
      itraconazole, posaconazole, and voriconazole in a head-to-head comparison.
      Posaconazole and itraconazole were the most active in vitro with MICs falling
      well below the achievable serum levels typically observed with standard dosing
      regimens.

PMID- 19107638
TI  - Occurrence and relevance of filamentous fungi in respiratory secretions of
      patients with cystic fibrosis--a review.
AB  - The colonization of airways by filamentous fungi and the development of
      respiratory infections require some predisposing factors as encountered in
      patients with cystic fibrosis (CF). Indeed, the defective mucociliary clearance
      which characterizes the disease is associated with local immunological disorders.
      In addition, the prolonged therapy with antibiotics and the use of corticosteroid
      treatments also facilitate fungal growth. An important fungal biota has been
      described in respiratory secretions of patients suffering from CF. Aspergillus
      fumigatus, Scedosporium apiospermum and Aspergillus terreus for filamentous fungi
      and Candida albicans for yeasts are the main fungal species associated with CF.
      Although less common, several fungal species including Aspergillus flavus and
      Aspergillus nidulans may be isolated transiently from CF respiratory secretions,
      while others such as Exophiala dermatitidis and Scedosporium prolificans may
      chronically colonize the airways. Moreover, some of them like Penicillium
      emersonii and Acrophialophora fusispora are encountered in humans almost
      exclusively in the context of CF. As fungal complications in CF patients are
      essentially caused by filamentous fungi the present review will not include works
      related to yeasts. In CF patients, fungi may sometimes be responsible for
      deterioration of lung function, as occurs in allergic broncho-pulmonary
      aspergillosis (ABPA) which is the most common fungal disease in this context.
      Additionally, although the clinical relevance of the fungal airway colonization
      is still a matter of debate, filamentous fungi may contribute to the local
      inflammatory response, and therefore to the progressive deterioration of the lung
      function.

PMID- 19107639
TI  - A skin infection mimicking chromoblastomycosis by a Capnodialean fungus.
AB  - Most black fungi that are repeatedly involved in human infection belong to the
      order Chaetothyriales. Capnodialean melanized fungi often thrive in extreme
      environments like rock surfaces and hypersaline microhabitats. They are able to
      grow meristematically with very thick cellular walls, resembling muriform cells
      of agents of chromoblastomycosis. In this report we describe a member of the
      order Capnodiales causing a chromoblastomycosis-like infection in human skin.
      However, in tissue the fungus presented with toruloid hyphae and intercalary,
      chlamydospore-like conidia with transversal septa, rather than with muriform
      cells. Judging from ITS rRNA sequences, the fungus is related to, but clearly
      different from, the genera Catenulostroma and Pseudotaeniolina; members of these
      genera are environmental and only rarely occur on human hosts.

PMID- 19107640
TI  - Rapid diagnosis of tuberculous pleuritis by a T-cell interferon-gamma release
      assay.
AB  - To obtain a correct diagnosis of tuberculous pleuritis by analysis of pleural
      effusions with standard diagnostic tools is difficult. Mycobacterium tuberculosis
      (MTB)-specific enzyme-linked immunosorbent assay (ELISA) or MTB-specific enzyme
      linked immunospot assay (ELISpot) on peripheral blood was not useful because the
      judgment was indeterminate or negative. However, we recently encountered 2 cases
      in which tuberculous pleuritis was rapidly diagnosed by performing MTB-specific
      ELISpot on pleural effusion mononuclear cells (PEMCs), because high levels of MTB
      specific cells by ELISpot were demonstrated in pleural effusion of patients with
      tuberculous pleuritis. to analyze MTB-specific T-cells in pleural effusion
      mononuclear cells by ELISpot is feasible in routine clinical practice and may be
      useful for a rapid and accurate diagnosis of tuberculous pleuritis.

PMID- 19107641
TI  - PTPN22 C1858T polymorphism and human brucellosis.
AB  - The PTPN22 gene encodes for an intracellular lymphoid-specific phosphatase (Lyp)
      that has a negative regulatory effect on T-cell activation. The minor allele of
      the single nucleotide polymorphism (SNP) in the PTPN22 gene encoding the Lyp
      tyrosine phosphatase has been associated with multiple autoimmune disorders and
      with susceptibility to M. tuberculosis. It is possible, therefore, that variants
      of this gene may also be involved in susceptibility to another intracellular
      pathogen, B. melitensis, which gives rise to human brucellosis. Accordingly, we
      studied 111 patients with brucellosis and 150 healthy controls who had had no
      prior contact with the pathogen. Genotyping of the PTPN22 1858CT was performed by
      an allele discrimination assay with TaqMan 5'. We found no statistically
      significant differences between the patients and the controls in genotype or
      allele frequencies of PTPN22 1858CT. These data suggest that this variant is not
      associated with human brucellosis.

PMID- 19107643
TI  - Tracking the transition from sublexical to lexical processing: on the creation of
      orthographic and phonological lexical representations.
AB  - Participants read aloud nonword letter strings, one at a time, which varied in
      the number of letters. The standard result is observed in two experiments; the
      time to begin reading aloud increases as letter length increases. This result is
      standardly understood as reflecting the operation of a serial, left-to-right
      translation of graphemes into phonemes. The novel result is that the effect of
      letter length is statistically eliminated by a small number of repetitions. This
      elimination suggests that these nonwords are no longer always being read aloud
      via a serial left-to-right sublexical process. Instead, the data are taken as
      evidence that new orthographic and phonological lexical entries have been created
      for these nonwords and are now read at least sometimes by recourse to the lexical
      route. Experiment 2 replicates the interaction between nonword letter length and
      repetition observed in Experiment 1 and also demonstrates that this interaction
      is not seen when participants merely classify the string as appearing in upper or
      lower case. Implications for existing dual-route models of reading aloud and
      Share's self-teaching hypothesis are discussed.

PMID- 19107642
TI  - Relationship between antidepressant and anxiolytic/hypnotic prescribing: a mixed
      methods study.
AB  - BACKGROUND: Antidepressant prescribing has dramatically increased in Scotland,
      and the cause is unknown. OBJECTIVE: To investigate if the increase in
      antidepressant prescribing coincided with a reduction in prescribing of
      anxiolytics and hypnotics; to investigate this relationship at practice level;
      and to explore whether general practitioners (GPs) explain the increase by their
      increased use for anxiety. METHODS:  STUDY DESIGN: analysis of routine
      prescribing data and interviews with GPs. SETTING: Scottish general practices.
      PARTICIPANTS: 942 practices included in the analysis. Sixty-three GPs in 30
      practices completed interviews. MAIN OUTCOME MEASURES: Quantity of
      antidepressants, anxiolytics, and hypnotics prescribed. Relationship at practice
      level between anxiolytic/hypnotic and antidepressant prescribing. Spontaneous
      comments by GPs about prescribing antidepressants for anxiety. RESULTS:
      Antidepressant prescribing increased from 28.9 million defined daily doses (DDDs)
      in 1992/3 to 128.3 million in 2004/5. Anxiolytic/hypnotic prescribing fell from
      64.2 million to 55.1 million DDDs. There was a weak, positive correlation between
      levels of antidepressant and anxiolytic/hypnotic prescribing (+0.084, p=0.010).
      GPs treated anxiety with antidepressants, although many described an overlap
      between anxiety and depression. Some spontaneously identified a relationship with
      benzodiazepine prescribing when asked to explain the increase in antidepressant
      prescribing. CONCLUSION: A small part of the increase in antidepressant
      prescribing is due to substitution for benzodiazepines to treat anxiety.

PMID- 19107644
TI  - Cesarean section is associated with more frequent pneumothorax and respiratory
      problems in the neonate.
AB  - We have investigated whether the incidence of neonatal pneumothorax (NP), use of
      mechanical ventilation (MV) or Continuous Positive Airways Pressure (CPAP) is
      increased in neonates delivered at term and preterm by cesarean section (CS). All
      deliveries at Ulleval University Hospital, Oslo, during the period 2001-2005
      (n=29,358) were included, among whom 5,957 were delivered by CS (20.3%). Data
      were collected on mode of delivery, elective or emergency CS, gestational age,
      maternal age, gender and parity. Among the 26,664 neonates born at term (> or
      =37th gestational week), 4,546 were delivered by CS (17.0%), of whom 0.5% by
      elective and 0.6% by emergency CS with NP. The incidence of diagnosed NP was
      significantly higher after CS than after vaginal delivery (0.6% vs. 0.10%,
      p<0.001). In addition, the need for MV was significantly increased (0.41% vs.
      0.19%; p=0.01) but use of CPAP was not (0.28%vs. 0.15%; p=0.08). Among 2,694
      neonates born preterm (<37th gestational week), 1,266 were delivered by CS
      (47.0%). The incidence of diagnosed NP was 2.05% when delivered by CS but only
      0.63% when delivered vaginally (p<0.01). Among the preterm infants delivered by
      CS, 17.7% needed CPAP compared to 6.9% when delivered vaginally (p<0.001) and MV
      was required for 8.1 and 3.7% (p<0.001), respectively. Among neonates delivered
      at term or moderately preterm (30-36 weeks) by CS the incidence of NP and other
      respiratory problems was significantly increased.

PMID- 19107645
TI  - Evolution of glioblastoma.

PMID- 19107646
TI  - Tympanic-ossicular prostheses and MEMS technology: whats and whys.
AB  - CONCLUSIONS: Microelectromechanical systems (MEMS) technology fulfils the
      requirements of implantable middle ear devices and consequently it becomes an
      excellent option to design and develop the related transducers. OBJECTIVES: To
      present a summarized overview of the fundamentals of mechanical technologies in
      relation to middle ear implants research. MATERIALS AND METHODS: Analysis of the
      possibilities, limitations and practical applications of MEMS as regards the
      research, development, transference and fabrication processes. RESULTS: MEMS is a
      new technology with the potential to develop small integrated mechanical and
      electronic systems that share many processes of integrated circuits technology
      and its wide application potential. Middle ear prostheses are essentially special
      implantable transducers that mimic the properties of the tympano-ossicular
      system: electromechanical systems that deliver low energy pulses safely and
      efficiently into the labyrinth fluids. They primarily require: active mechanisms
      to preclude potential damage levels; minimum energy consumption; adequate
      dimensions for the middle ear; and biotolerable materials. Additionally,
      development and translational aspects of the selected technology are of utmost
      importance in this field.

PMID- 19107647
TI  - Urethrography in the male: the clamp method.
AB  - BACKGROUND: Retrograde urethrography is considered the gold standard for
      evaluating stenosis or urethral disease. PURPOSE: To describe the clamp method
      for optimizing retrograde urethrography (RUG) using a perfected device and a drip
      infusion system. material and methods: RUG was performed in 42 patients with a
      mean age of 63.4+/-16.5 years suspected of having urethral stenosis. The
      modifications to the device are shown, and the steps of the technique described.
      The intensity of pain from both catheterization and external compression was
      measured on a visual analog scale (VAS). RESULTS: All the RUG examinations were
      conducted satisfactorily. The use of the drip infusion system enabled
      visualization of the posterior urethra in 97.6% of cases, and bladder repletion
      was achieved in 95.2% of cases. The urethrograms revealed images of stenosis in
      31 patients. With catheterization the mean pain intensity registered by VAS was
      0.7+/-0.6 (SD), whereas with external compression the mean pain intensity was
      0.06+/-0.02 (SD). CONCLUSION: The clamp method and drip infusion system used in
      this study are efficient and reduce patient discomfort. The procedure makes it
      possible to assess cases with stenosis close to the meatus that are difficult to
      manage with the conventional method.

PMID- 19107648
TI  - Fossa trochanterica of the proximal femur in rabbits: an anatomic structure for
      potential misinterpretation on magnetic resonance images.
AB  - BACKGROUND: Magnetic resonance imaging (MRI) has been increasingly used as an
      investigational tool for assessing the structure and function of animal skeletal
      disease models. However, to date, MRI tomographic knowledge of laboratory animal
      skeletal anatomy and pathology remains limited. PURPOSE: To demonstrate that
      fossa trochanterica of the proximal femur in rabbits can potentially be
      misinterpreted as a bone lesion on MR images. MATERIAL AND METHODS: Twenty 28-30
      week-old male New Zealand white rabbits were used in the study. Corticosteroid
      induced osteonecrosis induction was carried out with a combined administration of
      lipopolysaccharide and methylprednisolone. In this animal model, it is known that
      osteonecrosis commonly occurs in the proximal femur. MRI at 1.5 T was performed
      before osteonecrosis induction, and at 1 and 2 weeks post-osteonecrosis
      induction. For anatomical imaging of the proximal femur, coronal sectional images
      were obtained to align the femoral head, neck, and proximal shaft in a single
      plane. Volumetric computed tomography (CT) comprised continuous axial
      acquisitions through the bilateral hip joints and femurs and was performed on one
      age- and sex-matched New Zealand white rabbit to correlate MRI anatomical
      findings. RESULTS: In 30% of the acquired normal data sets, a low-signal area
      surrounded by high-signal bone marrow was observed slightly distal to the femoral
      head and medial to the third trochanter. This dark, low-signal area resembled an
      osteonecrosis lesion on MR images. Volumetric CT clarified that the low MR signal
      was due to the deep fossa trochanterica structure in the rabbit proximal femur.
      CONCLUSION: Improved understanding of the cross-sectional anatomy of the fossa
      trochanterica in the rabbit proximal femur will prevent misinterpretation as a
      bone lesion on MR images.

PMID- 19107649
TI  - Clinical use of circulating nucleosomes.
AB  - Nucleosomes, complexes of DNA and histone proteins, are released from dying and
      stressed cells into the blood circulation. Concentrations of circulating
      nucleosomes in plasma and serum are frequently found to be elevated in various
      cancers, and also in such acute conditions as stroke, trauma, and sepsis as well
      as in autoimmune diseases. The first part of this review focuses on the
      structural and functional properties of nucleosomes, the potential sources of
      nucleosome release into the circulation, the metabolism of circulating
      nucleosomes, and their pathophysiological role in disease. It goes on to describe
      the relevance of circulating nucleosomes in the diagnosis and prognosis of non
      malignant conditions such as sepsis, stroke, and autoimmune disease. Finally, it
      describes the clinical value of nucleosomes in the diagnosis, staging, prognosis,
      and monitoring of therapy in cancer; in particular, their potential as a new
      diagnostic tool for the early estimation of response to cytotoxic cancer therapy
      is emphasized.

PMID- 19107650
TI  - Intestinal bacteria and inflammatory bowel disease.
AB  - Crohn's disease (CD) and ulcerative colitis (UC) are the two principal forms of
      inflammatory bowel disease (IBD). Animal studies show that bacteria are involved
      in the etiology of IBD, and much is now known about the inflammatory processes
      associated with CD and UC, as well as the underlying genetic, environmental, and
      lifestyle issues that can affect an individual's predisposition to these
      diseases. However, while a number of candidate microorganisms have been put
      forward as causative factors in IBD, the primary etiologic agents are unknown.
      This review discusses the potential role of luminal and mucosal microbial
      communities in the etiology of IBD, and outlines studies that have been made
      using a variety of biotherapeutic therapies, involving the use of antibiotics,
      probiotics, prebiotics, and synbiotics.

PMID- 19107652
TI  - Long-term effects for acute phase myocardial infarct VEGF165 gene transfer
      cardiac extracellular matrix remodeling.
AB  - BACKGROUND: Cardiac remodeling is ultimately regulated by components of the
      extracellular matrix (ECM). We investigated the important role that growth
      factors play in the regulation of ECM remodeling that occurs as a consequence of
      myocardium damage. METHODS AND RESULTS: Rats were submitted to the ligation of
      the left anterior coronary artery and pcDNA3-vascular endothelial growth factor
      (VEGF)(165) was immediately injected intramyocardially in the treated group. The
      animals were divided into large size myocardium infarction (LMI) and small size
      myocardium infarction, with or without gene transfer. The plasmid-containing DNA
      encoding VEGF(165) was injected into the cardiac muscle and its effect was
      observed on the ECM components. Glycosaminoglycans were identified and quantified
      by agarose gel based electrophoresis and ELISA as well as immunocytochemistry to
      examine specific cathepsin B, heparanase, and syndecan-4 changes. The amounts of
      hyaluronic acid (HA; p < 0.005), DS, chondroitin sulfate, and heparan sulfate (p
      < 0.001) were significantly increased in the LMI treated group in comparison to
      the other groups, which correlates with the decrease in the expression of
      heparanase. A decrease in the molecular mass of HA was found in the scar tissue
      of treated group. CONCLUSIONS: The data obtained strongly support the idea that
      changes in the ECM and its components are important determinants of cardiac
      remodeling after myocardium infarct and may be essential for inflammatory
      response and attempt to stabilize the damage and provide a compensatory
      mechanisms to maintain cardiac output since the ECM components analyzed are
      involved with angiogenesis, cell proliferation and differentiation.

PMID- 19107654
TI  - The link between prosody and language skills in children with specific language
      impairment (SLI) and/or dyslexia.
AB  - BACKGROUND: Children with specific language impairment (SLI) and dyslexia are
      known to have impairments in various aspects of phonology, which have been
      claimed to cause their language and literacy impairments. However, 'phonology'
      encompasses a wide range of skills, and little is known about whether these
      phonological impairments extend to prosody. AIMS: To investigate certain prosodic
      abilities of children with SLI and/or dyslexia, to determine whether such
      children have prosodic impairments, whether they have the same pattern of
      impairments, and whether prosodic impairments are related to language and
      literacy deficits. METHODS & PROCEDURES: Six subtests of the Profiling Elements
      of Prosodic Systems - Child version (PEPS-C) were used to investigate
      discrimination/comprehension and imitation/production of prosodic forms that were
      either independent of language or that had one of two linguistic functions:
      chunking (prosodic boundaries) and focus (contrastive stress). The performance of
      three groups of 10-14-year-old children with SLI plus dyslexia, SLI, and dyslexia
      were compared with an age-matched control group and two younger control groups
      matched for various aspects of language and reading. OUTCOMES & RESULTS: The
      majority of children with SLI and/or dyslexia performed well on the tasks that
      tested auditory discrimination and imitation of prosodic forms. However, their
      ability to use prosody to disambiguate certain linguistic structures was impaired
      relative to age-matched controls, although these differences disappeared in
      comparison with language-matched controls. No, or only very weak, links were
      found between prosody and language and literacy skills in children with SLI
      and/or dyslexia. CONCLUSIONS & IMPLICATIONS: Children with SLI and/or dyslexia
      aged 10-14 years show an impaired ability to disambiguate linguistic structures
      for which prosody is required. However, they are able on the whole to
      discriminate and imitate the actual prosodic structures themselves, without
      reference to linguistic meaning. While the interaction between prosody and other
      components of language such as syntax and pragmatics is problematic for children
      with SLI and/or dyslexia, prosody itself does not appear to be a core impairment.

PMID- 19107653
TI  - Inhibition of histone deacetylases antagonized FGF2 and IL-1beta effects on MMP
      expression in human articular chondrocytes.
AB  - Fibroblast growth factor-2 (FGF2) and interleukin-1beta (IL-1beta) stimulate the
      expression of matrix metalloproteinases (MMPs) in articular chondrocytes, which
      may contribute to cartilage degradation and development of osteoarthritis.
      Histone deacetylases (HDACs) have recently been implicated in the regulation of
      MMP gene expression. To investigate the functional involvement of HDACs in the
      signaling pathway of FGF2 and IL-1beta, we examined the effects of HDAC
      inhibition on activities of FGF2 or IL-1beta on gene expression of MMP-1, MMP-3,
      MMP-13, a disintegrin and metalloproteinase with thrombospondin motifs-5
      (ADAMTS5), collagen type II, and aggrecan. Human articular chondrocyte cultures
      were treated with FGF2 or IL-1beta in the presence or absence of HDAC inhibitor
      (trichostatin A, TSA). Gene expression levels after treatments were assessed
      using quantitative real time PCR. Results showed that FGF2 and IL-1beta both
      increased MMP-1 and -13 expression, while IL-1beta also increased MMP-3 mRNA
      levels. These effects were attenuated in the presence of TSA in a dose dependent
      manner. In contrast to the effects on MMPs, FGF2 decreased mRNA levels of ADAMTS
      5, which was not affected by HDAC inhibition. FGF2, IL-1beta, and TSA inhibited
      expression of aggrecan, while TSA also decreased mRNA levels of collagen type II.
      These findings showed that HDAC inhibition antagonized FGF2 and IL-1beta induced
      MMP expression. Combination of FGF2 and the HDAC inhibitor decreases both
      anabolic and catabolic genes, which may slow the cartilage turnover and be
      beneficial for maintaining cartilage integrity.

PMID- 19107655
TI  - Acquired dysarthria in conversation: identifying sources of understandability
      problems.
AB  - BACKGROUND: Acquired progressive dysarthria is traditionally assessed, rated, and
      researched using measures of speech perception and intelligibility. The focus is
      commonly on the individual with dysarthria and how speech deviates from a
      normative range. A complementary approach is to consider the features and
      consequences of dysarthric speech as it is produced as a turn-at-talk in everyday
      interaction and in particular the ways in which this talk may be identified by
      its recipient as problematic to understand. AIMS: To investigate how dysarthric
      turns-at-talk in everyday conversation may be problematic to understand. Further,
      to describe how recipients of dysarthric talk identify the source of problematic
      understandings to the dysarthric speaker. METHODS & PROCEDURES: Video data of
      natural conversation from two dyads were selected for this paper. The dyads were
      video-recorded at home, at 3-monthly intervals, over a maximum period of 18
      months. Using the methods of conversation analysis a collection of sequences was
      identified and transcribed. The sequences were analysed with reference to how the
      recipients of dysarthric talk, through the use of other-initiations of repair,
      identified some element of that talk as problematic. OUTCOMES & RESULTS: This
      work shows how a recipient of a dysarthric talk turn in everyday conversation
      goes about displaying the problematicity of that turn to its speaker. Whilst
      displaying that a problem exists with a prior turn, the recipient may have
      difficulty in knowing what that problem actually is. CONCLUSIONS & IMPLICATIONS:
      It is proposed that clinicians and researchers should consider the effects of
      dysarthric speech in interaction. Specifically, the nature of dysarthric troubles
      and the practices used to signal understanding problems as they occur in everyday
      interaction should be fully explored. This consideration may have relevance for
      clinical assessment and intervention.

PMID- 19107657
TI  - Real-word repetition as a predictor of grammatical competence in Italian children
      with typical language development.
AB  - BACKGROUND: Non-word repetition in children is a skill related to, but separable
      from grammatical ability. Lexical skill may bridge the gap between these two
      abilities. AIMS: The main aim was to determine whether real-word-repetition tasks
      could be better as predictors of grammatical ability than non-word-repetition
      tasks in children with typical language. This proposal was pursued because
      lexical knowledge was assumed to make performance in repetition tasks more
      representative of other language abilities, whereas non-word-repetition tasks are
      heavily influenced by phonological short-term memory. METHODS & PROCEDURES: In
      order to investigate this possibility, three repetition tasks (two real-word
      lists characterized by different lexical knowledge and one non-word list), were
      compared in three groups of three- to four-year-olds with typical language (42
      children). Grammatical ability was tested through probes for third-person plural
      inflection and direct-object critic use. OUTCOMES & RESULTS: Real words were
      repeated more accurately than non-words and the non-words were more sensitive to
      Syllable length than real words. Performance on all repetition tasks was
      correlated with grammatical ability, but real words predicted variance in
      grammatical ability to a greater extent than non-words. CONCLUSIONS &
      IMPLICATIONS: Given the lexical information contained in real words, repetition
      of such words was a better predictor of grammatical ability than non-word
      repetition. Future research should replicate and extend these results. Tasks
      using real words may also have considerable clinical potential; for this reason,
      these tasks might also be included in studies of children with language
      impairment.

PMID- 19107656
TI  - Direct versus indirect and individual versus group modes of language therapy for
      children with primary language impairment: principal outcomes from a randomized
      controlled trial and economic evaluation.
AB  - BACKGROUND: Many school-age children with language impairments are enrolled in
      mainstream schools and receive indirect language therapy, but there have been, to
      the authors' knowledge, no previous controlled studies comparing the outcomes and
      costs of direct and indirect intervention delivered by qualified therapists and
      therapy assistants, and each delivery mode offered to children individually or in
      groups. AIMS: To investigate the relative effectiveness of indirect and direct
      intervention therapy modes delivered individually or in groups for children with
      primary language impairment. METHODS & PROCEDURES: A multi-centre randomized
      controlled trial investigated 161 children with primary language impairment aged
      6-11 years randomized to a usual-therapy control group or to direct individual,
      indirect individual, direct group or indirect group therapy modes. Intervention
      was delivered three times a week for 30-40-min sessions in mainstream schools
      over 15 weeks. Language performance was assessed at baseline, post-therapy and at
      12 months. Cost analysis was based on salary and travel costs for intervention
      modes and usual therapy. OUTCOMES & RESULTS: Compared with controls, children
      receiving project therapy made short-term improvements in expressive (p = 0.031),
      but not receptive, language immediately following intervention. Children with
      specific expressive language delay were more likely to show improvement than
      those with mixed receptive-expressive difficulties. The four project therapy
      modes did not differ on primary language outcomes (all p-values>0.392) and there
      were no further improvements evident at follow-up. Indirect group therapy was the
      least costly mode, with direct individual therapy the most costly. CONCLUSIONS &
      IMPLICATIONS: Intervention in this age group can be effective for expressive
      language and can be delivered equally effectively though speech and language
      therapy assistants and to children in groups.

PMID- 19107658
TI  - Children with speech, language and communication needs: their perceptions of
      their quality of life.
AB  - BACKGROUND: This study is part of a programme of research aiming to develop a
      quantitative measure of quality of life for children with communication needs. It
      builds on the preliminary findings of Markham and Dean ( 2006 ), which described
      some of the perception's parents and carers of children with speech language and
      communication needs had regarding children's experience of quality of life.
      However, this earlier study did not observe and evaluate the perceptions of
      children themselves and consequently left a vital gap in the evidence. The study
      reported here seeks to address this by describing the quality of life experiences
      reported by children and young people themselves. AIMS: The study aimed to
      provide a qualitative, child-centred, description of the quality of life
      experiences of children and young people with speech language and communication
      needs. METHODS & PROCEDURES: The study used a qualitative methodology to provide
      a credible and thick description of the quality of life experiences of children
      and young people with speech language and communication needs. Children and young
      people participating in the study were selected to represent a range of speech
      and language pathologies, according to their capacity to comprehend and
      participate within the data-collection activities. A modified focus group
      technique was used as a method of data collection and data were analysed
      according to the principles of Grounded Theory and Framework analysis. OUTCOMES &
      RESULTS: Seven focus group interviews were conducted with a range of children and
      young people in full-time education and in receipt of speech and language
      therapy. The data showed a number of key themes regarding children's quality of
      life experiences. These themes ranged from the participant's perceptions of what
      improves their daily lives to the difficulties they experience and consequently
      the negative impacts perceived on their quality of life. CONCLUSIONS &
      IMPLICATIONS: This study illuminates the quality of life experiences of children
      with speech language and communication needs. The findings are of direct benefit
      to clinicians, researchers, and policy-makers alike as they broaden the
      understanding of children's speech and language difficulties. Despite the
      potential bias inherent in qualitative research with children, the findings
      provide support for the development of a quality of life scale for children with
      speech language and communication needs. Such an outcome measure would enable
      clinicians and researchers to quantify children's quality of life, thereby
      broadening the range of clinical outcomes available.

PMID- 19107659
TI  - Qualitative study of the therapeutic relationship in speech and language therapy:
      perspectives of adults with acquired communication and swallowing disorders.
AB  - BACKGROUND: Considerations of the negotiated therapeutic relationship in speech
      and language therapy are somewhat scarce, with specific therapeutic factors
      generally framed from psycholinguistic, behavioural, or neurological
      perspectives. AIMS: To explore the therapeutic relationship in speech and
      language therapy, focusing on the personal meanings and experiences of adult
      clients with acquired communication and swallowing disorders. METHODS &
      PROCEDURES: The study was qualitative, using methods from Grounded theory to
      analyse eleven interviews with adults who had acquired disorders of communication
      or swallowing, as they described their perceptions of speech and language therapy
      and therapists. Five males and six females with a mean age of 62 years, ranging
      from 25 to 87 years, with varied communication disorders, were interviewed.
      OUTCOMES & RESULTS: A preliminary theoretical framework explains how speech and
      language therapists supported alienated, demoralized or confused clients with
      therapeutic qualities, such as Being Understanding, Being Gracious, Being Erudite
      and Being Inspiring; and with therapeutic actions, such as Being Confident, Being
      Soothing, Being Practical and Being Empowering. These categories provided a basis
      for the researcher to construct a substantive theory of restorative poise which
      characterized the attitudinal and behavioural characteristics of an ideal speech
      and language therapist from the perspective of the client. CONCLUSIONS &
      IMPLICATIONS: Participants were aware of the components of a therapeutic
      relationship and valued these as essential to their own personal understanding of
      positive outcomes in speech and language therapy. Therefore, specific types of
      attitudes and actions that constitute the speech and language therapist's
      contributions to the therapeutic relationship seemed to provide catalytic
      conditions for successful working together in therapy; and consequently, may have
      a bearing on effective practice and treatment efficacy.

PMID- 19107660
TI  - Psychosocial outcomes in a weight loss camp for overweight youth.
AB  - OBJECTIVE: There is good evidence that youth attending weight loss camps in the
      UK and US are successful at achieving weight loss. Limited research suggests
      improvement in body image and self-esteem as well. This study evaluated changes
      in eight psychosocial variables following participation in a weight loss camp and
      examined the role of gender, age, length of stay, and body mass index (BMI) in
      these changes. METHODS: This was an observational and self-report study of 130
      participants (mean age = 12.8; mean BMI = 33.5; 70% female; 77% Caucasian). The
      program consisted of an 1800 kcal/day diet, daily supervised physical activities,
      cooking/nutrition classes, and weekly psycho-educational/support groups led by
      psychology staff. Participants completed measures of anti-fat attitudes, values
      (e.g., value placed on appearance, athletic ability, popularity), body- and self
      esteem, weight- and health-related quality of life, self-efficacy, and depressive
      symptoms. RESULTS: Participants experienced significant BMI reduction (average
      decrease of 7.5 kg [standard deviation, SD = 4.2] and 2.9 BMI points [SD = 1.4]).
      Participants also exhibited significant improvements in body esteem, self-esteem,
      self-efficacy, generic and weight-related quality of life, anti-fat attitudes,
      and the importance placed on appearance. Changes in self-efficacy, physical
      functioning and social functioning remained significant even after adjusting for
      initial zBMI, BMI change, and length of stay. Gender differences were found on
      changes in self-efficacy, depressive symptoms, and social functioning.
      CONCLUSION: Participation in weight loss programs in a group setting, such as a
      camp, may have added benefit beyond BMI reduction. Greater attention to changes
      in psychosocial variables may be warranted when designing such programs for
      youth.

PMID- 19107661
TI  - The welfare and suitability of primates kept as pets.
AB  - Amid growing concern about keeping exotic species as companion animals, nonhuman
      primates have been highlighted as inappropriate for private ownership. However,
      there has been no comprehensive review of the suitability of primates as pets,
      using a framework such as Schuppli and Fraser's (2000). Schuppli and Fraser
      incorporate welfare of the individual, of others, and of the environment. This
      article (a) examines the numbers, origins, ages, and ownership trends of primates
      kept as pets in the United Kingdom and (b) identifies a number of welfare,
      health, and environmental concerns. Overall, strong evidence supports the
      argument that primates are not suitable pets; it is unlikely that the welfare of
      pet primates can be adequately addressed in normal households. Finally, using
      unpublished data on complaints and inquiries received by the Royal Society for
      the Prevention of Cruelty to Animals, the study assesses the degree of public
      concern about the welfare of primates kept as pets in England and Wales. The
      article identifies a wide range of concerns about keeping pet primates and
      concludes that this practice should end.

PMID- 19107662
TI  - The effect of feeding enrichment on the moloch gibbon (Hylobates moloch).
AB  - This study explored the effect of 3 feeding devices (food-filled baskets,
      polyvinyl chloride tubes, frozen ice pops) on the behavior of 4 zoo-housed moloch
      gibbons. The project studied the gibbons for 5 days during a control condition
      (no feeding enrichment) and 5 days per condition of feeding enrichment, when 3 of
      the same type of feeding device were suspended within the animals' exhibit. The
      gibbons interacted with the feeders an average of 172.25 times. The animals
      showed no significant difference in the total number of times that they
      interacted with the 3 different feeding devices but were slower to approach the
      food-filled tubes than the baskets or ice pops. There was no sign of habituation
      to any of the feeding devices over their 5 days of presentation. Feeding
      enrichment significantly influenced certain components of the gibbons' behavior.
      The animals spent more of the observation time outside and showed more instances
      of foraging and fewer occurrences of moving during the enrichment conditions than
      the control. The study concluded that feeding devices may offer a viable form of
      environmental enrichment for captive moloch gibbons.

PMID- 19107663
TI  - A comparison of Bahamian cat and dog caregivers on New Providence.
AB  - This article offers the first comparison of actions and attitudes of Afro
      Caribbean caregivers who keep only cats or only dogs. A total of 330 Bahamian
      caregivers found that women primarily keep cats; men primarily keep dogs. Cat
      keepers were more attached to their companion animals but no more sensitive
      toward nonhuman animal-welfare issues than dog keepers. When considering actions
      toward pets, the study noted few differences between the two types of caregivers.
      Both types reported low neutering rates and lack of confinement. Findings suggest
      that although both cat and dog caregivers thought themselves good pet caregivers,
      both types would benefit from animal-welfare education. In communities where cat
      populations pose a threat to indigenous wildlife and current care-keeping
      practices may be a cause for concern, caregivers may need education as to the
      implications of their actions. Given the similarity in dog-keeping practices in
      the West Indies, the findings about cat caregivers reported here may be
      applicable to other Afro-Caribbean communities. Further research on cats should
      be done to allow better understanding of the dynamics and behavior of cat
      populations on small islands.

PMID- 19107664
TI  - The sizes of elephant groups in zoos: implications for elephant welfare.
AB  - This study examined the distribution of 495 Asian elephants (Elephas maximus) and
      336 African elephants (Loxodonta africana) in 194 zoos, most of which were
      located in Europe (49.1%) and North America (32.6%). Cows outnumbered bulls 4 to
      1 (Loxodonta) and 3 to 1 (Elephas). Groups contained 7 or fewer: mean, 4.28
      (sigma = 5.73). One fifth of elephants lived alone or with one conspecific. Forty
      six elephants (5.5%) had no conspecific. Many zoos ignore minimum group sizes of
      regional zoo association guidelines. The American Zoo and Aquarium Association
      recommends that breeding facilities keep herds of 6 to 12 elephants. The British
      and Irish Association of Zoos and Aquariums recommends keeping together at least
      4 cows over 2 years old. Over 69% Asian and 80% African cow groups-including
      those under 2 years-consisted of fewer than 4 individuals. Recently, Europe and
      North America have made progress with some zoos no longer keeping elephants and
      with others investing in improved facilities and forming larger herds. The
      welfare of individual elephants should outweigh all other considerations; zoos
      should urgently seek to integrate small groups into larger herds.

PMID- 19107665
TI  - Risk factors and remediation of self-injurious and self-abuse behavior in rhesus
      macaques.
AB  - Considered signs of decreased welfare--abnormal behaviors such as self-injury and
      self-abuse among nonhuman primates housed in the laboratory--may put into
      question the validity and reliability of scientific research using these animals
      as models. Providing environmental enrichment decreases the incidence of some
      undesirable behaviors but is often unsuccessful at ameliorating the most severe
      types of abnormal behaviors. To prevent such behaviors from developing, it is
      important to identify risk factors that provide insight into the causes of
      certain abnormal behaviors. This study confirmed previous research identifying
      nursery rearing, single housing, and time spent in single housing as important
      risk factors. Results also indicate that the number of cage relocations affects
      the development of these behaviors. In addition, this study presents new data on
      comorbidity of several abnormal behaviors and discusses possible reasons for
      these patterns.

PMID- 19107666
TI  - Primate location preference in a double-tier cage: the effects of illumination
      and cage height.
AB  - Nonhuman primates are frequently housed in double-tier arrangements with
      significant differences between the environments of the upper and lower-row
      cages. Although several studies have investigated whether this arrangement alters
      monkeys' behavior, no studies have addressed the two most notable differences,
      light and height, individually to determine their relative importance. This
      experiment examined how rhesus and long-tailed macaques allocated their time
      between the upper and lower-row cages of a 1-over-1 apartment module under
      different lighting conditions. In Condition A, monkeys' baseline degree of
      preference for the upper- and lower-row was tested. In Condition B, the lighting
      environment was reversed by limiting illumination in the upper-row cage and
      increasing illumination in the lower-row cage. In both conditions, monkeys spent
      more time in the upper-row cage, thus indicating a strong preference for
      elevation regardless of illumination. The amount of time that monkeys spent in
      the lower-row cage increased by 7% under reversed lighting, but this trend was
      not significant. These results corroborate the importance of providing captive
      primates with access to elevated areas.

PMID- 19107667
TI  - Re: "The poor contribution of chimpanzee experiments to biomedical progress".

PMID- 19107668
TI  - Delivery of hypoxia-inducible VEGF gene to rat islets using polyethylenimine.
AB  - Islet transplantation is a promising strategy for treatment of diabetes. However,
      islets are exposed to hypoxia in the process of isolation and transplantation and
      prone to apoptosis. Vascular endothelial growth factor (VEGF) gene transfer is
      one of the promising strategies to address this problem. However, VEGF expression
      in the cells under normoxia is undesirable since it may induce pathological
      angiogenesis. Therefore, VEGF expression should be regulated to avoid this
      problem. In this study, hypoxia-inducible VEGF gene was transferred to islets
      using a non-viral carrier. Rat islets were transfected with high molecular weight
      PEI (25 kDa, PEI25K), low molecular weight PEI (2 kDa, PEI2K), and polyamidoamine
      dendrimer (PAMAM). PEI25K had higher transfection efficiency to rat islets than
      PAMAM or PEI2K. The hypoxia-inducible gene expression vector, pRTP801-Luc or
      pRTP801-VEGF was transferred to rat islets using PEI25K. Transfection assay with
      pRTP801-Luc showed that luciferase expression was induced in rat islets under
      hypoxia. In addition, transfer of pRTP801-VEGF showed that VEGF gene expression
      was higher under hypoxia than normoxia in rat islets. In conclusion, delivery of
      pRTP801-VEGF using PEI25K induces VEGF level specifically under hypoxia and may
      be useful for the development of anti-apoptotic strategies for islet
      transplantation.

PMID- 19107672
TI  - Skin and surface lead contamination, hygiene programs, and work practices of
      bridge surface preparation and painting contractors.
AB  - A 2005 regulatory review of the lead in construction standard by the Occupational
      Safety and Health Administration (OSHA) noted that alternative pathways of
      exposure can be as significant as inhalation exposure and that noncompliance with
      the standard pertaining to hygiene facilities and practices was the second most
      commonly violated section of the standard. Noncompliance with provisions of the
      standard and unhealthy work and hygiene practices likely increase the likelihood
      of take-home lead via contaminated clothing, automobiles, and skin, thus
      contributing to elevated blood lead levels (BLL) among construction workers and
      their family members. We performed a cross-sectional study of bridge painters
      working for small contractors in Massachusetts to investigate causes of
      persistent elevated BLLs and to assess lead exposures. Thirteen work sites were
      evaluated for a 2-week period during which surface and skin wipe samples were
      collected and qualitative information was obtained on personal hygiene practices,
      decontamination and hand wash facilities, and respiratory protection programs.
      Results showed lead contamination on workers' skin, respirators, personal
      automobiles, and the decontamination unit, indicating a significant potential for
      take-home lead exposure. Overall, the geometric mean (GM) skin lead levels ranged
      from 373 microg on workers' faces at end of shift to 814 microg on hands at break
      time. The overall GM lead level inside respirators was 143 microg before work and
      286 microg after work. Lead contamination was also present inside workers'
      personal vehicles as well as on surfaces inside the clean side of the
      decontamination unit. Review of the respiratory protection programs, work site
      decontamination and hand wash facilities, and personal hygiene practices
      indicated that these factors had significant impact on skin and surface
      contamination levels and identified significant opportunities for improving work
      site facilities and personal practices. Elevated lead exposure and BLL can be
      minimized by strict adherence to the OSHA provisions for functioning
      decontamination and hygiene facilities and healthy personal hygiene practices.

PMID- 19107673
TI  - Magnetic resonance colonography in clinical use: how far have we come?

PMID- 19107674
TI  - Ets-1 is increased in anticancer drug-containing media and hypoxic cultures,
      similar to TACE.

PMID- 19107675
TI  - Multidrug resistant enteroaggregative Escherichia coli diarrhoea in rural
      southern Indian population.
AB  - Enteroaggregative Escherichia coli (EAEC) has been implicated in acute and
      persistent diarrhoea in children, adults, and in HIV/AIDS patients.
      Enteroaggregative Escherichia coli strains isolated from different parts of the
      world show a low to high level resistance to antimicrobial agents. The aim of the
      present study was to determine antimicrobial susceptibility in vitro among 64
      EAEC strains isolated from children and adults with diarrhoea. 270 E. coli
      strains were isolated from children and adults. A total of 64 were identified as
      EAEC by multiplex PCR targeting 2 specific genes, AggR and EAST, from July 2006
      to July 2007. Susceptibility to various antibiotics was checked using the Kirby
      Bauer disk diffusion method. Disk diffusion testing for 11 commonly used
      antimicrobial agents showed EAEC resistant to trimethoprim sulfamethoxazole,
      ampicillin and nalidixic acid. 75% of strains isolated showed multidrug
      resistance, i.e. resistance to >3 antimicrobial agents. Most of the isolates
      showing multidrug resistance were from children below 5 y of age. An increase in
      resistance of EAEC strains to quinolones was observed in the study. Our study
      indicated that EAEC resistance in southern India is much higher than that
      reported from other parts of country. Our study also showed that monitoring
      sensitivity to antibiotics commonly used in acute and persistent diarrhoea is
      necessary for optimum selection of effective antibiotics and elimination of
      antibiotics with little therapeutic value. Further clinical epidemiological and
      laboratory studies are needed to clarify these issues.

PMID- 19107676
TI  - Prolonged impact of a one-week course of clindamycin on Enterococcus spp. in
      human normal microbiota.
AB  - Human intestinal Enterococcus spp. was monitored during a 2-y period after 7 d
      clindamycin treatment. Consecutive faecal samples were collected from 8 healthy
      volunteers, 4 of whom had received clindamycin. After treatment, the number of
      enterococcal colonies was diminished and species variation extended. Erythromycin
      and clindamycin resistance increased from 19% to 69% and 0% to 67%, respectively.
      Elevated resistance levels lasted up to 9 months and erm(B) was detected in
      samples up to 6 months. Our results show that the clindamycin treatment had a
      prolonged impact on resistance and species variation.

PMID- 19107677
TI  - Clinical correlates of generalized worry in multiple sclerosis.
AB  - Anxiety disorders are common in multiple sclerosis (MS). Chronic worry is the
      defining feature of generalized anxiety. Despite this, only one study has
      examined the impact of chronic worry in MS. The present investigation explored
      the relationship between excessive worry and common physical, emotional, and
      neuropsychological symptoms in a community-based sample of 50 patients with
      relapsing-remitting and secondary progressive MS. As expected, MS patients
      reported significantly more worry than a group of 45 healthy controls.
      Correlational analyses revealed that MS patients' elevated worry was associated
      with fatigue, sleep disturbance, problem-solving deficits, pain, and disability
      status. Follow-up analyses indicated that worry and anxiety may represent related
      but distinct constructs. Clinicians are urged to regularly monitor and treat
      pathological worry in MS.

PMID- 19107678
TI  - Prenatal expressions of hyperpolarization-activated cyclic-nucleotide-gated
      channel (HCN) genes in dysplastic hippocampi in rats.
AB  - AIM: Hyperpolarization-activated cyclic nucleotide-gated (HCN or h-channel)
      channels mediate hyperpolarization-activating currents in the hippocampus and
      neocortex. The aim of this study is to present prenatal h-channel gene
      expressions (HCN1 and HCN2; HCN1-Entrez-Gene ID: 84390; HCN2- Entrez Gene ID:
      114244) in dysplastic hippocampal pyramidal neurons induced by in utero
      irradiation in rats. MATERIALS AND METHODS: Time-pregnant Wistar albino rats were
      irradiated and the dysplastic hippocampus in their 2 month-old litters was
      studied. Gene expression was studied by RNA extraction and polymerase chain
      reaction methods. RESULTS: None of the rats showed seizure activity. mRNA levels
      of HCN1 and HCN2 genes were decreased especially in the CA1 and CA3 pyramidal
      neurons in the hippocampi of experimental rats; however, the differences were not
      significant compared to controls. In CA2, mRNA levels of both genes were
      increased and this rise did not reach significant level. The CA4 sub-region
      showed a different pattern of expression: HCN1 increased but HCN2 decreased
      insignificantly compared to controls. CONCLUSION: Our results demonstrated that
      dysplastic neurons showed decreased levels of mRNA expression of HCN1 and HCN2
      genes, in particularly CA1 and CA3 pyramidal neurons. The rationale for how these
      changes contribute to epileptogenesis in dysplastic tissues still requires
      further studies.

PMID- 19107680
TI  - Tumors of the lateral ventricle: the factors that affected the preference of the
      surgical approach in 46 patiens.
AB  - AIM: Optimal surgical pathway for lateral ventricle tumors is still
      controversial. The purpose of this study is to discuss the factors that affected
      the preference of the surgical techniques for removing lateral ventricle tumors.
      MATERIAL AND METHODS: 46 consecutive patients underwent operation for lateral
      ventricle tumors. The mean age was 36 years. Preoperative magnetic resonance
      imaging (MRI) images were examined to determine the location, expansion and size
      of each tumor. The transcallosal approach was used in 25 patients, and the
      transcortical approach was used in 21 patients. We performed MRI to determine the
      tumor size and recurrence or increased size of the residual tumor. RESULTS: Total
      resection was performed in 31 patients. Only one patient, with glioblastoma, died
      due to hepatic encephalopathy and intraventricular hemorrhage after the
      operation. Additional neurological deficits were seen 4 patients, and
      postoperative seizure occurred in one patient. The mean duration of follow-up was
      38,37 months. CONCLUSION: Lateral ventricle tumors can be treated best by careful
      selection of the surgical approach according to localization of the tumor within
      the ventricle, the expansion side of the tumor, the size of the tumor, the origin
      of the vascular feeding branches, the venous drainage, and the relationship of
      the structures, and the histopathological features.

PMID- 19107679
TI  - Efficacy of prognostic factors on survival in patients with low grade glioma.
AB  - AIM: In this report, we aim to determine the prognostic factors influencing the
      length of survival in patients with low-grade gliomas. MATERIAL AND METHODS: In a
      retrospective evaluation, we have reviewed fiftythree patients who had been
      operated between the years of 1980 and 2006. The diagnoses of the patients were
      histopathologically verified as low-grade glioma(LGG). The medical records of the
      patients were reviewed for age, gender, tumor locations, extent of resection, and
      presence of seizure, the neurological status as defined by the Karnofsky
      Performance Scale (KPS) and radiotherapy treatment after surgery as possible
      prognostic factors. RESULTS: Median cumulative survival time for all the patients
      with LGG was 141+/-14.83 months. Median survival time was 216+/-78.52 months for
      astrocytoma Grade I; 115+/-8.22 months for astrocytoma Grade II, and 242+/-76.36
      months for oligodendroglioma. Young age, histology subtype (oligodendroglioma)
      and preoperative KPS were determined to have positive influence on survival
      according to Log Rank Test. In contrast, age, histology type and the extent of
      resection remained independent prognostic factors upon survival when Cox
      Regression Backward Stepwise (Wald) method was performed. CONCLUSION: It can be
      concluded that surgery seems to be an appropriate first step option in the
      treatment of LGG.

PMID- 19107681
TI  - Nogo-A inhibitory peptide (NEP1-40) increases pan-cadherin expression following
      mild cortical contusion injury in rats.
AB  - BACKGROUND: Nogo-A is a myelin-associated neurite outgrowth inhibitory protein
      that limits elongation of central nerve fibers, neuronal regeneration and
      plasticity. We investigated the effect of delivering an inhibitory peptide that
      neutralizes Nogo-A on neuronal recovery following mild cortical contusion injury.
      METHODS: 41 rats were allocated into the control and NEP1-40 treatment groups.
      PBS was applied following trauma over the parietal cortex after opening the dura
      in the control group. NEP1-40 solution was immediately applied following trauma
      after opening the dura in the treatment group. Each group was further divided
      into 3 subgroups and sacrificed on the third, eighth, and 21st days after injury.
      The brains were removed for analysis. RESULTS: Immunohistochemical staining of
      the injured cortex for pan-cadherin revealed a significant increase in staining
      in the NEP 1-40 treatment group at the 8th and 21st days after injury. Electron
      microscopic evaluation revealed better cytoarchitectural preservation in the
      axons of the animals treated with NEP 1-40. CONCLUSION: We observed improved
      preservation of injured neurons after topical application of NEP 1-40 following
      mild cortical injury. Pan-cadherin expression may correlate with the recovery of
      neurons and axonal bodies. Electron microscopical findings confirmed better
      preservation of neuronal structures after NEP1-40 treatment. Pan-cadherin is a
      good marker for neuronal recovery after cortical injury.

PMID- 19107682
TI  - Review of a series with abducens nerve palsy.
AB  - OBJECTIVE: In this report, we aimed to investigate the patients that presented at
      our clinic complaint with diplopia due to the abducens nerve palsy and
      neurosurgical disease. METHODS: The study design was a retrospective review of
      ten cases with the abducens nerve palsy. The causes of the abducens nerve
      paralysis of our patients were as follows: two cases with head trauma, three
      cases with pituitary tumors, one case with sphenoid sinus mucocele, one case with
      greater superficial petrosal nerve cellular schwannoma at the petrous apex, one
      case with hypertensive intraventricular hemmorhage, one case with hydrocephalus,
      and one case with parotid tumor and skull base/brain stem invasion. RESULTS:
      Depending on the location of the lesion, the symptoms due to nuclear damage
      showed no improvement as in our case with adenocarcinoma of the parotid gland.
      The lesions sited at the subarachnoid portion of the abducens nerve or in the
      cavernous sinus, the abducens nerve palsy improved or botilinum injection was
      performed during recovery period. CONCLUSION: We presented abducens nerve palsy
      cases due to neruosurgical disorders. A botilinum injection was performed in
      three patients with the abducens palsy. Botilinum injection can help patients
      with sixth nerve palsy during the recovery period.

PMID- 19107683
TI  - Surgical outcome in hippocampal sclerosis following selective amygdalo
      hippocampectomy.
AB  - OBJECTIVES: Temporal lobe epilepsy is the most common form of intractable partial
      epilepsy in adults with hippocampal sclerosis accounting for the majority of
      cases. Selective amygdalo-hippocampectomy (SEAH) is suggested as a safe and
      effective surgical procedure with the advantage of a better cognitive outcome.
      METHODS: We prospectively documented 56 consecutive patients with medically
      refractory medial temporal lob epilepsy. Candidates for surgery were determined
      as those with characteristic clinical and imaging findings, ictal recordings, and
      neuropsychological evaluation. A standard SEAH was performed and hippocampal
      sclerosis was histologically confirmed. RESULTS: In our study 76.7% of patients
      were classified as Engel I and 62.2% as ILAE I at their last follow up. Overall,
      at the last follow-up, 51.8% of patients were seizure-free since surgery (Engel
      1a and ILAE 1a), 25% had stopped antiepileptic treatment, and another 52% had
      decreased either the dosage or number of antiepileptic drugs. 86.3% of the
      patients with abnormality on neurocognitive tasks showed improvement at the end
      of the 6 months post surgery. CONCLUSION: SEAH is a safe and effective surgical
      procedure without the necessity of a larger resection and further invasive
      methods.

PMID- 19107684
TI  - Early post operative visual outcome in microsurgically treated suprasellar
      meningiomas predict long-term visual outcome.
AB  - BACKGROUND: Different data exist regarding long-term visual prognosis associated
      with suprasellar meningiomas. The aim of this study was to determine the outcome
      of suprasellar meningiomas with respect to short and long-term visual outcomes.
      METHOD: During the period of 1997 to 2006, 45 patients were operated either
      through a pterional (30) or bifrontal (15) approach. Visual parameters were
      evaluated early and late post-operatively. RESULTS: 5 patients died post
      operatively and 2 cases failed to attend follow up. During the early post
      operative period, 15 (39.5%) showed improvement and 9 (23.7%) worsening of vision
      among 38 patients. Patients were followed-up for 1 to 8 years with mean of 4.1
      years. Follow-up data revealed that 26 (68.4%) patients had visual improvement in
      at least one eye (10 of them in both eyes) while 10 (26.3%) patients had visual
      deterioration in one or both eyes. Data showed no significant correlation between
      visual outcome and extent of tumor removal or surgical approach. Visual outcome
      was better in patients with preoperative vision > 1mfc (p-value=0.001). Data also
      showed that early post-op vision significantly correlates with long term visual
      outcome (p-value =0.003). CONCLUSION: Visual outcome is better in patients with
      preoperative vision > 1 mfc and early post-operative vision significantly
      correlates with long term visual outcome.

PMID- 19107685
TI  - When should ventriculoperitoneal shunt placement be performed in cases with
      myelomeningocele and hydrocephalus?
AB  - AIM: The shunt infection rates vary from 2 to 39% among complications related to
      shunts used for hydrocephalus treatment. Shunt infections are reported to be more
      common than any other etiologies in newborn babies with myelomeningocele.
      MATERIAL AND METHODS: In this study, we performed a retrospective evaluation of
      94 MM and HS cases that were treated in our clinics between 1994 and 2005.
      Comparisons of shunt infection rates of cases that had surgical placement of VPS
      either at a different session (group A) or in the same session (Group B) with
      repair of MM sac were made. RESULTS: Sixty three patients were grouped in group A
      and 31 cases in group B. MM sac operation site wound infection was seen in 7
      versus 5 cases, CSF fistula in 5 versus 3 cases and VPS infection in 9 versus 6
      cases in group A and B respectively. 6 patients had meningitis in both groups.
      CONCLUSION: These data indicate that ventriculoperitoneal shunt placement in the
      same session of MM sac repair in patients with HS is not an acceptable practice.
      We therefore believe in VPS placement in a separate session by confirming absence
      of infection after MM sac repair surgery.

PMID- 19107686
TI  - Spontaneous regression of extruded lumbar disc herniation: report of two
      illustrative case and review of the literature.
AB  - Although the first reported surgery for lumbar disc herniation was published many
      years ago, there still remains little agreement for the most effective treatment
      protocol for symptomatic cases. Many patients with extruded lumbar disc
      herniation require surgical intervention due to radiculopathy of lower
      extremities but some neurological symptoms of intervertebral disc herniation may
      frequently improve with conservative treatment. In this paper, two cases of
      spontaneous regression of extruded lumbar herniated discs are presented. The disc
      regressions of two patients were correlated with clinical improvement and
      documented with follow up MRI studies. Additionally the clinical course of lumbar
      disc herniation was discussed with mechanisms, features of MRI,
      immunohistological pathology and treatment options of past clinical studies.

PMID- 19107688
TI  - Extremely delayed renal cell carcinoma metastasis mimicking convexity meningioma.
AB  - Cerebral extra-axial metastases mimicking meningioma are extremely rare. Imaging
      characterictics may not always differentiate between meningioma and metastatic
      tumors. A 68-year-old-woman who had been operated for renal cell carcinoma 20
      years ago presented with new symptoms of an intracranial mass lesion. A large
      extra-axial convexity mass destroying the calvarium and dura was excised with
      Simpson Grade I removal. The pathology examination revealed metastatic carcinoma.
      Such tumors that satisfy several criteria for a diagnosis of meningioma, but
      prove instead to be metastatic carcinoma form the focus of our discussion. A
      meticulous clinical evaluation and histopathological diagnosis is essential in
      patients with an intracranial mass whether the lesion looks like a primary or
      metastatic tumor on the first evaluation.

PMID- 19107687
TI  - Lumbar spinal chondroma presenting with radiculopathy: case report.
AB  - Chondroma is a very unusual cartilagenous neoplasm of the spine. Here we are
      present a case of spinal chondroma with radiculopathy. A 54-year-old female
      patient consulted with progressive low back pain and left femoral numbness.
      Lumbar spinal Magnetic resonance (MR) imaging studies showed an extradural mass
      lesion in the left L2 body. Computerized tomography (CT) did not reveal any
      osteolytic lesion of the bone. The mass lesion was excised totally by left
      partial hemilaminectomy and the intradural compartment was also checked. The
      histopathology of the lesion was confirmed as chondroma. Preoperative evaluation
      and meticulous pathological analysis are required because of the malignant
      transformation potential of these rare pathologies.

PMID- 19107689
TI  - Totally cystic intradural extramedullary schwannoma.
AB  - Totally cystic intradural extramedullary lesions are uncommon and form a
      different spectrum of conditions as compared to the commonly seen intradural
      extramedullary tumors. Spinal schwannomas are benign tumors arising from spinal
      nerve root sheaths and are the most common intradural extramedullary spinal
      tumors. Though cystic changes in schwannomas are well described, most spinal
      schwannomas are solid or heterogeneous solid tumors and a totally cystic
      schwannoma is uncommon. The authors describes a case of totally cystic intradural
      extramedullary schwannoma and stress the importance of complete contrast imaging
      to differentiate this rare but almost completely curable tumor from other common
      intradural cystic lesions of the spine.

PMID- 19107690
TI  - Dysphagia due to diffuse idiopathic skeletal hyperostosis of the cervical spine.
AB  - Diffuse idiopathic skeletal hyperostosis (DISH) or Forestier's disease is a
      common disorder of unknown etiology that is characterized by ossification of the
      anterior longitudinal ligament of the spine and various extra-spinal ligaments.
      We present the case of a 54-year-old woman with progressive dysphagia due to DISH
      of the cervical spine, which is a relatively rare pathology in neurosurgical
      practice. The cervical osteophytes extending from C2 to C4 and external
      compression of the pharyngoesophageal segment by the large osteophytes were
      demonstrated by X-ray, magnetic resonance imaging, and computed tomography.
      Surgical removal of the large osteophytes and a shortterm nonsteroidal anti
      inflammatory drug regimen led to the resolution of dysphagia. The clinical
      manifestations, diagnosis, and treatment of this unusual condition are discussed.

PMID- 19107691
TI  - Nasal-subfrontal giant schwannoma.
AB  - Subfrontal schwannomas are rare lesions. They can be misdiagnosed as olfactory
      meningiomas or neuroblastomas. We report a case of giant schwannoma involving the
      anterior cranial fossa; the frontal and ethmoid sinuses and nasal cavities. The
      patient presented with a year-long history of increasingly severe headache
      associated with insomnia. Examination revealed no neurological deficit except for
      the anosmia. Magnetic Resonance Imaging revealed a 9x5x3 cm intranasal-subfrontal
      extraaxial mass. Nasal biopsy indicated the presence of a schwannoma. The lesion
      was totally removed through a bifrontal craniotomy and the skull base was
      repaired with periosteal flap, fibrin glue and a split craniotomy graft. In
      addition to the cosmetic advantages over standard transfacial approaches, the
      extended subfrontal approach also provides early dissection of neural tissues,
      avoiding an inadvertent cerebrospinal fluid leak.

PMID- 19107692
TI  - Posttraumatic infarction in the basal ganglia after a minor head injury in a
      child: case report.
AB  - We present a case of posttraumatic infarction in the territory supplied by the
      lateral lenticulostriate artery after a minor head injury in a child. A 2.5-year
      old child was admited to our emergency room after a head-on fall from a height of
      50cm. He developed a right hemiparesis and he could not speak properly for about
      half an hour. An initial computerized tomography of the head taken two hours
      after the accident was normal. A follow-up CT obtained two days later revealed a
      hypodense lesion at the left basal ganglia and a diffusion-weighted magnetic
      resonance imaging disclosed an area of infarction. The patient was conservatively
      medicated and full recovery was made in three weeks. Hospital admission, careful
      observation and early diffusion-weighted MR examination should be considered for
      patients with persistent neurological deficits.

PMID- 19107693
TI  - Ossified chronic subdural hematoma with armored brain.
AB  - Ossified chronic subdural hematoma is a very rarely seen entity. We present here
      a 22-year-old male who had presented with severe headache consequent to brain
      compression caused by bifronto-parieto-temporal ossified subdural hematoma. We
      evaluated our method and surgical intervention in the light of the literature.
      The question whether the ossified membrane should be excised or not excised in
      these cases is a matter of controversy. We think that an ossified membrane
      causing an armored brain appearance should be excised in symptomatic, young
      patients with prominent cerebral compression. During this dissection, the
      relatively thickened arachnoid mater provides a safe border.

PMID- 19107694
TI  - Sublabial transseptal approach to pituitary adenomas with special emphasis on
      rhinological complications.
AB  - OBJECTIVE: The aim of this presentation is to show that the sublabial transseptal
      transsphenoidal approach to pituitary adenomas is the least invasive anatomic
      route with the lowest postoperative complication rates. PATIENTS AND METHOD: This
      study was based on a retrospective analysis of 276 patients with a diagnosis of
      pituitary adenoma who were surgically treated via the sublabial transsphenoidal
      route. RESULTS: The overall complication rate of the presented series was 14.8%.
      The recurrence rate was 14.1%; there were no deaths or intranasal complications
      in this series. Postoperative rhinological complications, such as septal
      perforation, synechiae, and mucosal tear which impaired nasal function, occur
      rarely with this approach compared to other approaches. CONCLUSION: Besides the
      technical advantages of this approach, performance of the initial phase of the
      operation by an otorhinolaryngologic surgeon is the basis of the low intranasal
      complication rate in our series.

PMID- 19107695
TI  - Primary undifferentiated ovarian carcinoma diagnosed by its metastasis to brain:
      an unusual case report.
AB  - OBJECTIVES: Intracranial metastasis of ovarian tumours is rarely seen with an
      incidence 0.1- 5% but simultaneous diagnosis of primary undifferentiated
      carcinoma of the ovary and its CNS metastasis has not been published previously.
      MATERIAL AND METHODS: A 56-year-old woman presented with headache and visual
      disturbance. She underwent cranial MRI and abdominal ultrasound. RESULTS: On
      examination, a bilateral right homonymous hemianopia and left papilledema were
      found. Cranial MR showed multiple ring-enhancing intracranial tumours. A right
      ovarian mass measuring 100x85x135 mm was discovered with abdominal ultrasound.
      She underwent extensive gynecological surgery. The histopathological diagnosis
      was undifferentiated ovarian carcinoma which dedifferentiated from endometrioid
      type ovarian adenocarcinoma. A week after gynecologic surgery, the patient
      underwent surgery for a left occipital tumour which proved to be anaplastic
      carcinoma metastasis. The patient succumbed 15 months after the diagnosis.
      CONCLUSIONS: Although metastasis from undifferentiated ovarian carcinomas to the
      central nervous system have been published with the CNS disease often developing
      long after the initial diagnosis of primary tumour; simultaneous diagnosis of
      primary undifferentiated carcinoma of the ovary and its CNS metastasis as
      described in our case may rarely occur.

PMID- 19107696
TI  - Fatal intratumoral hemorrhage following ventriculo-peritoneal shunt.
AB  - Ventriculo-peritoneal shunt, one of the most common surgical procedures performed
      by neurosurgeons all over the world has been associated with a number of
      complications; the most common being infection and mechanical failure. Most of
      these complications tend to increase morbidity with prolonged hospital stay and
      cost. Though subdural, extradural or intracerebral hematomas have been described
      after ventriculo-peritoneal shunt placement, fatal intratumoral bleed has been
      very uncommon. The authors describe a case of basal ganglionic tumor in a 15-year
      old child who underwent emergency ventriculo-peritoneal shunt placement for
      associated hydrocephalus and deteriorating consciousness. She had a sudden
      deterioration following the procedure and imaging revealed massive intratumoral
      hemorrhage.

PMID- 19107697
TI  - Ruptured blister-like aneurysm of distal internal carotid artery: a distinct
      entity.
AB  - OBJECTIVE: Blister-like aneurysms are small hemispherical bulges that usually
      originate from the anteromedial wall of the distal internal carotid artery and
      cause significant subarachnoid hemorrhage. It is very important to recognize this
      novel lesion as a different type of aneurysm than ordinary berry aneurysms. CASE
      DESCRIPTION: We report the case of a 43-year-old man who underwent a diagnostic
      procedure and was awaiting surgery elsewhere before being transferred to our
      institution. A right sided blister-like aneurysm was seen on angiograms. Although
      the aneurysm bled intraoperatively, 2 clips were placed with one slightly
      catching the medial artery wall. The outcome was excellent. CONCLUSIONS: Since
      blister-like aneurysms are different than saccular aneurysms both morphologically
      and histologically, their treatment also differs making surgical exploration and
      standard clipping a more hazardous situation than usual. In fact, surgical
      decision for blister aneurysms should be individual with alternative plans in
      case the initial treatment strategy fails. Such a flexible strategy also
      necessitates preoperative cerebrovascular flow testing and a variety of
      additional hardware like encircling graft clips, microsutures or wrapping
      material ready in the operating room on top of traditional aneurysm clips.

PMID- 19107698
TI  - Micellar electrokinetic chromatography: methodological and instrumental advances
      focused on practical aspects.
AB  - This article reviews the latest methodological and instrumental improvements for
      enhancing sensitivity and resolution in MEKC-based determinations. On-line sample
      concentration (stacking, sweeping and combination of two protocols) and other on
      capillary approaches such as in-capillary derivatization and the coupling of flow
      injection systems with MEKC are the most relevant methodological approaches
      discussed for improving sensitivity. At the same time, changes in the BGE through
      the use of organic modifiers, ionic liquids, cations, CDs, non-ionic and
      zwitterionic surfactants, mixed micelles, vesicles and carbon nanostructures as
      well as 2-D CE and chemometric techniques for enhancing resolution are also
      considered in detail. Two instrumental approaches such as MS and LIF are also
      discussed, covering the proposals for overcoming the difficulties arising from
      the direct coupling of MEKC with MS and the excellent detection sensitivity
      achieved by LIF using the typical argon-ion laser and recent growth in the use of
      diode lasers as excitation sources. Some thoughts on potential future directions
      are also expressed.

PMID- 19107699
TI  - Recent progress in the use of ionic polymers as pseudostationary phases for
      electrokinetic chromatography.
AB  - This review is an account of the development, utilization, and characterization
      of polymeric pseudostationary phases (PSPs) for EKC since the previous review in
      this series in 2007. Improvements in performance by means of new polymeric phases
      and modifications to previously reported materials are described. The use of EKC
      and spectroscopic studies to characterize the interactions between polymeric PSPs
      and analytes is discussed. The application of polymeric PSPs for techniques or
      approaches to which they provide particular advantages is reviewed. Chief among
      these is the application of polymeric PSPs for the combination of EKC with MS
      detection.

PMID- 19107700
TI  - Recent advances in the methodology, optimisation and application of MEEKC.
AB  - MEEKC is an electrodriven separation technique. Oil-in-water microemulsions (MEs)
      and to a lesser extent water-in-oil MEs have been used in MEEKC as BGEs to
      achieve separation of a diverse range of solutes. The more common (oil-in-water)
      MEs are composed of nanometre-sized droplets of oil suspended in an aqueous
      buffer. Interfacial tension between the oil and aqueous phase is reduced close to
      zero by the presence of a surfactant and a co-surfactant. MEEKC is capable of
      providing fast and efficient separations for a wide range of acidic, basic and
      neutral, water-soluble and -insoluble compounds. This review details the advances
      in MEEKC-based separations from the period 2006 to 2008. Areas covered include
      online sample concentration, chiral separation, suppressed electroosmosis MEEKC,
      MEEKC-MS, and the use of MEEKC in predicting migration behaviour and solute
      characteristics. A fundamental introduction to MEEKC, along with the presentation
      and discussion of recent applications is also included.

PMID- 19107701
TI  - Non-aqueous capillary electrophoresis 2005-2008.
AB  - This review article presents recent developments and applications of non-aqueous
      capillary electrophoresis (NACE): The text covers the period from the previous
      review (L. Geiser, J. L. Veuthey, Electrophoresis 2007, 28, 45-57) to summer
      2008. We focus primarily on the analysis of pharmaceutical drugs by non-aqueous
      solvents in CZE within different matrices including phytochemical plant extracts
      and biological fluids. We also extend our discussion to other application fields
      (e.g. food material and environmental samples) and to chiral separations by NACE.
      This review focuses on practical aspects of NACE, illustrating which organic
      solvents and electrolytes are best suited for NACE analyses and their
      compatibilities with different detection techniques, including UV, LIF and MS.
      The review emphasizes the interests of using non-aqueous solvents in place of
      water for the analysis by CZE, and as an alternative to MEKC.

PMID- 19107702
TI  - CE-MS in metabolomics.
AB  - An overview of the use of CE-MS in the field of metabolomics is provided.
      Metabolomics is concerned with the comprehensive analysis of endogenous low
      molecular-weight compounds in biological samples. CE-MS has demonstrated to be a
      powerful technique for the profiling of polar metabolites in biological samples.
      This review covers the use of various CE separation modes, capillary coatings, MS
      analyzers, sample preparation techniques, and data analysis methods used in CE-MS
      for metabolomics. The applicability of CE-MS in metabolomics research is
      illustrated by giving examples of the analysis of bacterial extracts, plant
      extracts, urine, plasma, and cerebrospinal fluid samples. The relevant CE-MS
      metabolomics studies published between 2000 and 2008 are presented in tabular
      form, including information on sample type and pretreatment and MS detection
      mode. Future developments with regard to the use of alternative ionization
      techniques, the use of coupled separation systems and the potential of microchip
      CE systems for metabolomics are discussed.

PMID- 19107703
TI  - Advances in enantioselective separations using electromigration capillary
      techniques.
AB  - The most recent literature dealing with enantioselective separations and
      stereoselective analyses of chiral entities including especially pharmaceuticals,
      phytochemicals, biochemicals, agrochemicals, fine chemicals and specific test
      compounds by electromigration techniques such as CE, MEKC, MEEKC, CEC and
      microchip CE is reviewed. The review covers literature from 2007 until mid-2008,
      i.e. studies that were published after the appearance of the latest review
      article on that topic in Electrophoresis by Gubitz and Schmid (see
      Electrophoresis 2007, 28, 114). Particular attention is given to the description
      of new chiral selector systems, studies on separation mechanisms and applications
      in the above-specified electromigration techniques.

PMID- 19107704
TI  - Recent advances in IEF in capillary tubes and microchips.
AB  - The methodological advancements in CIEF in tubes and microchips during the period
      between 2002 and early 2008 are reviewed as a continuation of previous review by
      the same author (Electrophoresis 2002, 23, 3847-3857). After a brief
      introduction, the following topics related to CIEF technologies are addressed:
      the materials used to form capillary tubes and chips; modes of CIEF related to
      the detection schemes; coatings of the capillary walls; additives to the
      separation media; sample-loading methods; development of pI markers and their
      use; focusing time in relation to the length of the pH gradient; resolution in
      terms of a peak capacity; and, the reproducibility and precision of CIEF. Three
      principal detection methods are examined, i.e. ultraviolet absorption,
      fluorescence and MS. The coupling of CIEF with other electrokinetic separation
      methods and chromatography is discussed, including many multidimensional systems
      constructed for proteome analysis using mass spectrometric identification. The
      developments in the separation of non-covalent complexes and microorganisms are
      examined. After a short conclusion, this review ends with 176 references.

PMID- 19107705
TI  - Heart-cutting 2-D CE using multiple detection points for chiral analysis of
      native amino acids.
AB  - A new methodology based on heart-cutting 2-D CE in a single capillary was
      developed for the chiral separation of a mixture of 22 underivatized amino acids.
      The first dimension is performed in an achiral BGE (2.3 M acetic acid, pH 2.1)
      allowing the separation of the analytes as a function of their charge-to-radius
      ratio. A selected fraction from the first dimension is then separated in the
      second dimension in the presence of a chiral selector (+)-(18-crown-6)-2,3,11,12
      tetracarboxylic acid. Since the introduction of the second electrolyte is
      performed by pressure mobilization, capillaries with small id of 10 microm are
      used to limit the peak broadening due to Taylor dispersion. Double capacitively
      coupled contactless conductivity detector is used for monitoring the selection
      and the isolation of the fraction at the different steps of the analysis (voltage
      and pressure mobilization steps). This double detection allows calculating the
      voltage and pressure stop times in real-time analysis. This new methodology is
      applied with success for the chiral separation of different amino acids (D,L-Tyr,
      D,L-Trp and D,L-Thr) contained in a mixture of 22 native amino acids.

PMID- 19107706
TI  - Use of information feedback and attentional focus of feedback in treating the
      person with a hemiplegic arm.
AB  - BACKGROUND AND PURPOSE: Feedback about motor performance can induce either an
      internal focus of attention (about body movement) or an external focus of
      attention (about the effects on the environment) in the learner. The main aim of
      this pilot study was to examine the attentional focus of feedback given by
      physiotherapists during treatment of the hemiplegic arm. A second aim was to
      examine the frequency of feedback about motor performance during treatment.
      METHOD: A multi-methods design was used (quantitative and qualitative). Eight
      physiotherapists and eight patients with stroke were recruited from two
      hospitals. Data were collected by video recordings of treatment, interviews (both
      therapists and patients) and questionnaire (therapists). Information feedback,
      instructions and motivational statements were identified from the video
      recordings. Feedback and instructions were further grouped into internal focus,
      external focus or mixed focus of attention. Themes were drawn from the interview
      transcripts. Triangulation was used to provide corroborating information from the
      different data sets. RESULTS: Two hundred and forty-six of the total 1914
      statements identified in the videos were feedback, the rest comprising
      instructions and statements of motivation. Of the feedback statements, 236 of the
      total 247 identified had an internal focus. Therapist interviews and
      questionnaires revealed more external focus communication than actual treatment.
      CONCLUSIONS: Physiotherapists used instructions and statements of motivation more
      than feedback and directed the patient's attention more to body movement than
      movement effects. The outcome of this study may prompt clinicians' to examine the
      amount and the attentional focus of the feedback they use in their clinical
      practice, and to consider whether it is a most effective approach in light of
      current evidence.

PMID- 19107707
TI  - Home or away? Community rehabilitation following traumatic brain injury: a case
      report.
AB  - BACKGROUND AND PURPOSE: A case report of AJ, a 25 year old man who had a severe
      traumatic brain injury and required ongoing rehabilitation. This study
      illustrates that community based rehabilitation can be the medium of choice to
      meet a client's rehabilitation needs. METHOD: 3 separated episodes of
      rehabilitation were given over a two year period. Meaningful goals were
      negotiated with client and main carer throughout; the supportive and effective
      care system provided by his family allowed abilities to be maintained and
      progress between sessions and episodes of care. RESULTS: Goals were achieved in
      each rehabilitation episode, maintained and progressed in each treatment break,
      with incremental reduction in levels of dependency for AJ, and improvement in
      quality of life for him and his family. CONCLUSION: With a specialist
      professional team and good support network, the community is the environment of
      choice for rehabilitation of severely brain injured clients.

PMID- 19107714
TI  - Unexpected formation of a molecular tetraalkyl nickel complex from an
      olefin/nickel(0) system.

PMID- 19107708
TI  - Clinical screening of autonomic dysfunction in multiple sclerosis.
AB  - BACKGROUND AND PURPOSE: Multiple sclerosis (MS) can affect the autonomic nervous
      system. Although exercise may be beneficial for people with MS, those with
      autonomic dysfunction may have altered heart rate responses to exercise. We
      investigated the hypothesis that the pattern of increase in heart rate on
      commencement of a simple cycle test would be different in those participants with
      MS who had been shown to have autonomic dysfunction on laboratory testing
      compared with both control participants and MS participants not exhibiting
      autonomic involvement. METHOD: A controlled cohort study with a volunteer sample
      of 31 adults with MS (26 women, 5 men) with a mean age of 46 +/- 8.00 years (32
      60 years), a median Expanded Disability Severity Scale of 3 (1-6) and a mean
      duration since diagnosis of 10.3 years (0.1-39 years). Thirty-one age-matched,
      non-disabled, sedentary but healthy adults (26 women, 5 men) with a mean age of
      45 +/- 9.5 years (24-57) comprised the control group. Autonomic function was
      evaluated using continuous heart rate and blood pressure responses to rhythmical
      deep breathing, the Valsalva manoeuvre, passive postural change and a simple
      cycle test. RESULTS: There were no significant differences in age, height or
      weight (p < 0.05) between the two groups or on any of the autonomic test results
      (p < 0.05). Five participants with MS (16%) had abnormal autonomic function on
      laboratory testing, two of whom demonstrated an abnormal heart rate response to
      the cycle test. CONCLUSIONS: It is suggested that physiotherapists monitor the
      heart rate response to a dynamic exercise test in people with MS prior to
      prescribing an exercise programme to ensure patients' safety. Should the response
      appear delayed or attenuated, referral for more formal autonomic laboratory
      testing is recommended.

PMID- 19107717
TI  - Stimuli-responsive polymersomes as nanocarriers for drug and gene delivery.
AB  - Polymeric formulations (micelles, vesicles etc.) have emerged as versatile drug
      carriers due to their increased stability, site specificity, blood circulation
      resistance and thus overall potential therapeutic effects compared to liposomes.
      Furthermore, stimuli-responsive systems have been developed whose properties
      change after applying certain external triggers. Polymersomes are mainly composed
      of amphiphilic block copolymers that are held together in water due to strong
      physical interactions between the insoluble hydrophobic blocks, thus forming a
      bilayer morphology or, in the case of triblock copolymers, a bilayer-like
      morphology. Formation and destabilization of these assemblies is a consequence of
      external stimuli (temperature, pH, oxidation/reduction conditions etc.). This
      review focuses on recent developments concerning stimuli- responsive polymersomes
      made of amphiphilic block copolymers and their potential applications within the
      biomedical field.

PMID- 19107718
TI  - Unprecedented, low cytotoxicity of spongelike calcium phosphate/poly(ethylene
      imine) hydrogel composites.
AB  - Covalently crosslinked PEI hydrogels are efficient templates for calcium
      phosphate mineralization in SBF. In contrast to the PEI hydrogels, non
      crosslinked PEI does not lead to calcium phosphate nucleation and growth in SBF.
      The precipitate is a mixture of brushite and hydroxyapatite. The PEI/calcium
      phosphate composite material exhibits a sponge like morphology and a chemical
      composition that is interesting for implants. Cytotoxicity tests using
      Dictyostelium discoideum amoebae show that both the non-mineralized and
      mineralized hydrogels have a very low cytotoxicity. This suggests that next
      generation PEI hydrogels, where also the degradation products are non-toxic,
      could be interesting for biomedical applications.

PMID- 19107719
TI  - Preparation and properties of cyclodextrin/PNIPAm microgels.
AB  - A two-stage precipitation polymerization in aqueous solution was used to prepare
      beta-cyclodextrin/poly(N-isopropylacrylamide) (beta-CD/PNIPAm) core-shell
      microgels. At the first stage, core microgels with CD moieties were synthesized
      by precipitation copolymerization of N-isopropylacrylamide (NIPAm) with a
      monovinyl beta-CD monomer. At the second stage, using the core particles as
      seeds, PNIPAm shell were further added onto the seeds by NIPAm polymerization.
      The microgels were characterized by means of Zetasizer Nano-ZS dynamic light
      scattering, TEM, IR, NMR, DSC, and TGA measurements. Using paeonol as a model
      drug molecule, the release behaviors of the microgels were investigated. The
      result indicates that the core-shell microgels could respond to change in
      temperature. Furthermore, the release of paeonol was related to supramolecular
      inclusion behavior of beta-CD and temperature sensitivity of PNIPAm.

PMID- 19107721
TI  - Effects of early nightmares on the development of sleep disturbances in motor
      vehicle accident victims.
AB  - The present study prospectively examined the extent to which trauma-related
      nightmares affected the subsequent development of insomnia symptoms in 314 motor
      vehicle accident (MVA) victims. Participants were assessed in-hospital and at 2
      weeks, 6 weeks, 3 months, and 1 year post-MVA. Hierarchical linear regression
      analyses showed that 6-week PTSD symptoms (PTSS) and 3-month nightmares, but not
      2-week nightmares were positively associated with sleep onset and maintenance
      problems reported at 3-month post-MVA. Nightmares reported at 3-months post-MVA
      were positively associated with 1-year sleep maintenance problems. These findings
      highlight the dynamic relationship between PTSS and sleep problems as well as the
      potential importance of early intervention for trauma-related nightmares as a
      means to prevent sleep problems after a traumatic experience.

PMID- 19107722
TI  - Posttraumatic stress symptoms as a mediator between sexual assault and adverse
      health outcomes in undergraduate women.
AB  - This study investigated the links between sexual assault experiences,
      posttraumatic stress symptoms, and adverse physical health outcomes among
      undergraduate women. Existing research has demonstrated that posttraumatic stress
      disorder mediates the relationship between trauma exposure and physical health in
      general, but this has yet to be tested for sexual assault specifically. Using
      structural equation modeling, support was found for a model in which
      posttraumatic stress symptom severity partially mediates the association between
      sexual assault severity and self-reported health outcomes. An alternative model
      using depression symptoms did not meet the criteria for mediation. Implications
      for the physical health of sexual assault survivors are discussed.

PMID- 19107720
TI  - Hybrid multicomponent hydrogels for tissue engineering.
AB  - Artificial ECMs that not only closely mimic the hybrid nature of the natural ECM
      but also provide tunable material properties and enhanced biological functions
      are attractive candidates for tissue engineering applications. This review
      summarizes recent advances in developing multicomponent hybrid hydrogels by
      integrating modular and heterogeneous building blocks into well-defined,
      multifunctional hydrogel composites. The individual building blocks can be
      chemically, morphologically, and functionally diverse, and the hybridization can
      occur at molecular level or microscopic scale. The modular nature of the designs,
      combined with the potential synergistic effects of the hybrid systems, has
      resulted in novel hydrogel matrices with robust structure and defined functions.

PMID- 19107723
TI  - Acute intervention for trauma-related problems.

PMID- 19107724
TI  - Internet interventions for traumatic stress: a review and theoretically based
      example.
AB  - Trauma recovery Web sites are proliferating with limited supportive evidence for
      effectiveness. In this article, the authors review the current very early studies
      on trauma recovery Web sites highlighting the different approaches, the empirical
      support provided, and the critical development issues facing this exciting
      frontier. An example site based on social cognitive theory is also reviewed.

PMID- 19107726
TI  - Early intervention for trauma: where are we and where do we need to go? A
      commentary.
AB  - In this commentary, the author underscores the importance of early intervention
      for trauma and describes the challenges that lie ahead for researchers, decision
      makers, and care providers. The author also provides a review of where things
      stand, briefly reviews psychological first aid strategies, and underscores where
      we need to go from here. Although the field has advanced considerably in the last
      decade or so, and there are compelling trials underway, there is much work that
      needs to be done, especially in terms of effectiveness and the task of
      integrating early intervention into various work cultures, such as the military.

PMID- 19107725
TI  - Low cortisol, high DHEA, and high levels of stimulated TNF-alpha, and IL-6 in
      women with PTSD.
AB  - Posttraumatic stress disorder (PTSD) has been associated with hypothalamic
      pituitary-adrenal (HPA) axis and immune function alterations; however, few
      studies have simultaneously investigated these systems in participants with PTSD.
      In this study, HPA axis and immune function in 26 women with PTSD with and
      without major depressive disorder was compared to 24 traumatized controls and to
      21 nontraumatized controls. Posttraumatic stress disorder was associated with low
      cortisol and higher levels of DHEA and greater production of tumor necrosis
      factor-alpha (TNF-alpha) and interleukin-6 (IL-6) compared to traumatized and
      healthy controls. Women with PTSD and depression exhibited greater production of
      IL-6 and higher levels of dehydroepiandrosterone (DHEA) than those with PTSD, but
      without depression. These findings suggest dysregulated HPA axis and immune
      function in women with PTSD, and that comorbid depression may contribute to these
      abnormalities.

PMID- 19107727
TI  - Self-compassion and PTSD symptom severity.
AB  - Neff's (2003a, 2003b) notion of self-compassion emphasizes kindness towards one's
      self, a feeling of connectedness with others, and mindful awareness of
      distressing experiences. Because exposure to trauma and subsequent posttraumatic
      stress symptoms (PSS) may be associated with self-criticism and avoidance of
      internal experiences, the authors examined the relationship between self
      compassion and PSS. Out of a sample of 210 university students, 100 endorsed
      experiencing a Criterion A trauma. Avoidance symptoms significantly correlated
      with self-compassion, but reexperiencing and hyperarousal did not. Individuals
      high in self-compassion may engage in less avoidance strategies following trauma
      exposure, allowing for a natural exposure process.

PMID- 19107728
TI  - Using evidence to inform clinical practice shortly after traumatic events.
AB  - Despite ongoing gaps in our knowledge, there is now considerable research
      evidence available to inform clinical decisions and treatment plans shortly after
      traumatic events. The author uses two fictional cases to illustrate an evidence
      based approach to clinical management following traumatic events. The importance
      of fully assessing individuals and tailoring management plans to address their
      specific needs optimally is highlighted by considering two distinct, but familiar
      types of presentation.

PMID- 19107729
TI  - PTSD symptoms, forgiveness, and revenge among Israeli Palestinian and Jewish
      adolescents.
AB  - Exposure to political terror and its psychological toll were assessed in 276
      Israeli Palestinian and 1,469 Jewish adolescents using self-report
      questionnaires. Israeli Palestinians displayed more posttraumatic symptoms,
      higher levels of objective exposure to terror, more negative life events, lower
      ability to forgive, and a higher need for vengeance than their Jewish
      counterparts. Although the two groups did not differ in fear levels, Israeli
      Palestinians expressed more favorable attitudes toward peace. Ethnicity played a
      major role in explaining the variance of posttraumatic symptomatology. Israeli
      Palestinians displayed increased vulnerability to mental distress when compared
      to their Jewish counterparts. The unique roles of subjective fear, attitudes
      towards peace, forgiveness, and revenge among Israeli Palestinians are discussed.

PMID- 19107730
TI  - Respiratory sinus arrhythmia and cognitive functioning in children.
AB  - We examined associations between children's cognitive performance and both basal
      respiratory sinus arrhythmia (RSA) and RSA regulation to a reaction time task.
      Cognitive performance was examined in the lab via standardized tests of cognitive
      functioning (Woodcock-Johnson III) and a reaction time task. Results suggest that
      a higher level of basal RSA is predictive of better performance on WJ III scales
      examining fluid intelligence (e.g., working memory, cognitive efficiency). RSA
      reactivity was not significantly related to cognitive performance. Results build
      on and extend the literature by demonstrating that, in typically developing
      elementary school age children, RSA is related to well-standardized measures of
      cognitive performance even after controlling for potential confounds.

PMID- 19107731
TI  - Antioxidant and antiinflammatory effect of Epilobium parviflorum Schreb.
AB  - Epilobium parviflorum Schreb. (Onagraceae) is used for the treatment of benign
      prostatic hyperplasia (BPH), but its biological action is not entirely
      identified. This paper aims to report data on E. parviflorum with respect to its
      antioxidant and antiinflammatory effects. The aqueous acetone extract of E.
      parviflorum showed higher antioxidant effect in the DPPH assay than well known
      antioxidants and inhibited the lipid peroxidation determined by the TBA assay
      (IC(50) = 2.37 +/- 0.12 mg/mL). In concentrations of 0.2-15.0 microg/mL the
      extract possessed a protective effect, comparable to catalase (250 IU/mL),
      against oxidative damage, generated in fibroblast cells. In the COX inhibition
      assay E. parviflorum decreased the PGE(2) release, so showing inhibition of the
      COX-enzyme (IC(50) = 1.4 +/- 0.1 microg/mL).

PMID- 19107732
TI  - Retrospective evaluation of biopsychosocial determinants and treatment response
      in patients receiving devil's claw extract (doloteffin).
AB  - In a retrospective evaluation of patients taking part for 2 months in a
      postmarketing surveillance study on the effectiveness and safety of Harpagophytum
      procumbens, associations were found to known explanators of pain, disability and
      depression. Therefore, treatment non-responders might best be referred to a
      multimodal pain relief program that deals with fear avoidance beliefs, enhances
      experiences that decrease perceptions linking disability and pain and forces the
      patients to rethink the way they deal with the problem. However, during treatment
      with the aqueous Harpagophytum extract, this decision might reasonably be
      postponed to the end of month 4, since it has been shown that the maximum pain
      relief occurs after 3-4 months.

PMID- 19107733
TI  - Effect of adlay (Coix lachryma-jobi L. var. ma-yuen Stapf.) hull extracts on
      testosterone release from rat Leydig cells.
AB  - Adlay has been used as a traditional Chinese medicine for the treatment of many
      diseases. However, few studies have reported the effects of adlay seeds on the
      endocrine system. In the present study, the effects of methanol extracts of adlay
      hull (AHM) on testosterone synthesis were studied. Rat Leydig cells were
      incubated with different reagents including human chorionic gonadotropin, 8-bromo
      adenosine-3',5'-cyclic monophosphate, forskolin, A23187, progesterone and
      androstenedione in the presence or absence of AHM. The rat anterior pituitary
      (AP) gland was treated with gonadotropin-releasing hormone (GnRH) in vitro in the
      presence or absence of AHM, and the concentrations of luteinizing hormone (LH) in
      the media were measured. AHM decreased testosterone release via the inhibition of
      (1) the PKA and PKC signal transduction pathways, (2) 17beta-HSD enzyme activity
      in rat Leydig cells, and (3) in vitro GnRH-induced LH secretion.

PMID- 19107734
TI  - Dietary mucilage promotes regression of atheromatous lesions in
      hypercholesterolemic rabbits.
AB  - The antihypercholesterolemic and antiatherogenic effect of the mucilage
      galactomannan isolated from fenugreek seeds was studied in experimental rabbits
      maintained on a high cholesterol diet for 3 months. Changes in the levels of
      cholesterol and triglycerides in serum and tissues and aortic fatty lesions were
      analysed in animals receiving mucilage (40 mg/kg body weight) daily and compared
      with the control. A significant decrease in serum total cholesterol, LDL
      cholesterol and triglycerides and cholesterol and triglycerides in liver and
      aorta and a decrease in Sudan IV staining of aorta indicated
      antihypercholesterolemic and antiatherogenic effects of the mucilage. Regression
      studies showed that administration of mucilage for 3 months caused a significant
      decrease in serum total and LDL cholesterol and aortic cholesterol. Mucilage
      accelerated the regression of atheromatous lesions in the aorta as evidenced by
      significantly low sudanophilic staining. Recovery from inflammation in
      hypercholesterolemic animals receiving mucilage was evidenced by a faster
      decrease in C-reactive protein (CRP) in serum to basal levels. The lipid lowering
      and antiatherogenic effects of mucilage from fenugreek which is used as a food
      flavoring spice highlights the importance of dietary intervention in the
      regression of atherosclerosis.

PMID- 19107735
TI  - Echinacea as an antiinflammatory agent: the influence of physiologically relevant
      parameters.
AB  - Numerous Echinacea preparations are available on the market for the prevention
      and treatment of cold and 'flu symptoms and inflammatory conditions associated
      with infections. Most of these preparations are consumed orally in the form of
      aqueous or ethanol extracts and tinctures. Since the recommended consumption
      normally involves a brief local exposure to the diluted preparation at an
      unspecified time in relation to the actual infection, then it is important that
      experimental models for the evaluation of Echinacea reflect these limitations. A
      line of human bronchial epithelial cells, in which rhinoviruses stimulate the
      production of pro-inflammatory cytokines, was used to evaluate several relevant
      parameters. The chemically characterized Echinacea preparation (Echinaforce) was
      capable of inhibiting completely the rhinovirus induced secretion of IL-6
      (interleukin-6) and IL-8 (chemokine CXCL-8) in these cells, regardless of whether
      the Echinacea was added before or after virus infection, and in response to a
      range of virus doses. This inhibitory effect was also manifest under conditions
      resembling normal consumption with respect to the duration of exposure to
      Echinacea and the Echinacea dilution. It is concluded that under real life
      conditions of Echinacea consumption, the virus-induced stimulation of pro
      inflammatory cytokines can be effectively reversed or alleviated.

PMID- 19107736
TI  - Mangifera indica extract (Vimang) impairs aversive memory without affecting open
      field behaviour or habituation in rats.
AB  - Vimang is an aqueous extract of Mangifera indica L, used in Cuba for the
      treatment of immunopathological disorders. Increasing evidence from preclinical
      studies indicates that Vimang displays antioxidant, antiallergic, analgesic and
      antiinflammatory actions. The present study investigated the effects of systemic
      administration of Vimang on behavioural outcomes of neurological function in
      rats. A single oral administration of Vimang produced an impairment of short- and
      long-term retention of memory for aversive training when given either 1 h
      pretraining or immediately posttraining, but not 8 h posttraining. Vimang did not
      affect open field behaviour or habituation. The results indicate that Vimang
      might induce deficits of emotionally motivated memory without affecting
      nonassociative memory, locomotion, exploratory behaviour or anxiety.

PMID- 19107737
TI  - Trifolium L.--a review on its phytochemical and pharmacological profile.
AB  - Plants from the genus Trifolium have been used in traditional medicine by many
      cultures. In Turkish folk medicine, for example, some Trifolium species are used
      for their expectorant, analgesic, antiseptic properties and also to treat
      rheumatic aches. Some species are also grown as pasture crops for animals in the
      Mediterranean. The high quercetin concentration and soyasaponin occurrence make
      the seeds of some Trifolium species a potential source of health beneficial
      phytochemicals for use in human nutrition. However, Trifolium pratense has also
      gained popularity due to research into its use for the treatment for menopausal
      symptoms. This paper provides an overview of the phytochemical and
      pharmacological profile of Trifolium species.

PMID- 19107738
TI  - Effects of Microdesmis keayana alkaloids on vascular parameters of erectile
      dysfunction.
AB  - Microdesmis keayana (Pandaceae) is an African tropical plant whose roots are used
      in traditional medicine for erection impairment but the compounds responsible for
      its action are unknown. Two major alkaloids recently isolated from the roots of
      M. keayana, keayanidine B and keayanine, were tested for vasorelaxing properties
      using isolated rat aortic rings precontracted by phenylephrine to confirm its
      traditional use. Influence of the alkaloids on the endothelial production of
      endothelial nitric oxide synthase (eNOS) was measured by quantitative polymerase
      chain reaction (QPCR) analysis. Scavenging activities were assessed versus 1,1
      diphenyl-2-picrylhydrazyle (DPPH) and reactive oxygen species (ROS) such as
      superoxide anion (O(2)(*-) and hydrogen peroxide (H(2)O(2)) in cell-free and
      cellular systems. The results showed that keayanidine B and keayanine had
      significant vasorelaxing properties. This effect could be due to their strong
      antioxidant activity versus O(2)(*-) and H(2)O(2) and to their stimulation of
      eNOS mRNA expression. Therefore these alkaloids could indirectly stimulate NO
      production in the vascular bed and would explain the traditional use of M.
      keayana in erectile dysfunction.

PMID- 19107739
TI  - Genistein down-regulates the constitutive activation of nuclear factor-kappaB in
      human multiple myeloma cells, leading to suppression of proliferation and
      induction of apoptosis.
AB  - Because of the central role of transcription factor nuclear factor-kappaB (NF
      kappaB) in cell survival and proliferation in human multiple myeloma, the
      possibility of using it as a target for myeloma treatment was explored using
      genistein, an agent known to have very little or no toxicity in humans. It was
      found that NF-kappaB was constitutively active in two human myeloma cell lines
      examined and that genistein, a chemopreventive agent, down-regulated NF-kappaB in
      two cell lines as indicated by the electrophoretic mobility gel shift assay and
      prevented the nuclear retention of p65 as shown by immunocytochemistry. Two
      myeloma cell lines showed constitutively active Akt phosphorylation. Genistein
      suppressed the constitutive Akt phosphorylation. Genistein also down-regulated
      the expression of NF-kappaB-regulated gene products, including bcl-2, bcl-xl,
      cyclin D1 and ICAM-1. This led to the suppression of proliferation and induction
      of apoptosis. Overall, the results indicate that genistein down-regulates NF
      kappaB and phospho-Akt in human myeloma cells, leading to the suppression of
      proliferation and induction of apoptosis, thus providing the molecular basis for
      the treatment of myeloma patients with this pharmacologically safe agent.

PMID- 19107740
TI  - Protective effect of daidzin against D-galactosamine and lipopolysaccharide
      induced hepatic failure in mice.
AB  - This study examined the effects of daidzin, a major isoflavone from Puerariae
      Radix, on D-galactosamine (D-GalN) and lipopolysaccharide (LPS)-induced liver
      failure. Mice were given an intraperitoneal injection of daidzin (25, 50, 100 and
      200 mg/kg) 1 h before receiving an injection of D-GalN (700 mg/kg)/LPS (10
      microg/kg). Daidzin markedly reduced the elevated serum aminotransferase activity
      and the levels of lipid peroxidation and tumor necrosis factor-alpha. The
      glutathione content was lower in the D-GalN/LPS group, which was attenuated by
      daidzin. The daidzin pretreatment attenuated the swollen mitochondria observed in
      the d-GalN/LPS group. Daidzin attenuated the apoptosis of hepatocytes, which was
      confirmed using the terminal deoxynucleotidyl transferase-mediated dUTP nick end
      labeling method and a caspase-3 assay. Overall, these results suggest that the
      liver protection of daidzin is due to reduced oxidative stress and its
      antiapoptotic activity.

PMID- 19107741
TI  - Vitex agnus castus as prophylaxis for osteopenia after orchidectomy in rats
      compared with estradiol and testosterone supplementation.
AB  - Osteoporosis research undertaken in males is rare and there are only a few
      therapeutic options. Phytoestrogens might be a safe alternative for prophylaxis.
      Sixty 3-month-old male rats were orchidectomized and divided into five groups.
      The groups either received soy-free food (C), estradiol (E), testosterone (T) or
      Vitex agnus castus in different concentrations (AC high/AC low) for 12 weeks. The
      tibia metaphysis was tested biomechanically and histomorphometrically. The AC
      high group reached 87% of the biomechanical values of the estradiol group and was
      significantly superior to the control group. Testosterone supplementation
      resulted in poor biomechanical properties. The cortical bone parameters of the AC
      group were similar to the control group, while supplementation with estradiol and
      testosterone demonstrated a reduction of cortical bone. The AC high group reached
      88.4% of trabecular bone area, 80.7% of trabecular number and 66.9% of the number
      of trabecular nodes compared with estradiol supplementation. Vitex agnus castus
      demonstrated osteoprotective effects in males. It preserves the cortical as well
      as the trabecular bone and might be a safe alternative for HRT. Testosterone
      supplementation has positive effects on trabecular bone, which are concurrently
      counteracted by the loss of cortical bone.

PMID- 19107742
TI  - Screening of selected food and medicinal plant extracts for pancreatic lipase
      inhibition.
AB  - Lipids are important components in human nutrition; however, their increased
      intake contributes to the development of obesity and can lead to multiple long
      term complications. Pancreatic lipase (triacylglycerol acylhydrolase, EC 3.1.1.3)
      is a key enzyme for the absorption of dietary triglycerides. Interference with
      fat hydrolysis results in the reduced utilization of ingested lipids, therefore
      inhibition of lipases decreases fat absorption. Extracts from 106 species of
      medicinal plants, vegetables and fruits were screened for potential lipase
      inhibitory activity. p-Nitrophenylpalmitate and 5-bromo-4-chloro-3
      indoxylpalmitate were used as substrates in an in vitro test with crude porcine
      pancreatic lipase. Bearberry (Arctostaphylos uva-ursi), garden pea (Pisum
      sativum), Norway spruce (Picea abies) and large-leaved lime (Tilia platyphyllos)
      extracts were the most active. Additionally, the activity of selected extracts
      with removed polyphenols was measured. Extracts of bearberry, garden pea and
      large-leaved lime are a promising source for developing functional foods or
      isolating active compounds.

PMID- 19107743
TI  - Yeast hydrolysate induces longitudinal bone growth and growth hormone release in
      rats.
AB  - This study investigated the growth promoting effects of yeast extract (YH) fed to
      Sprague-Dawley male rats (3 weeks old) for 4 weeks. The negative (N)-control and
      positive (P)-control groups were given a daily oral administration of saline and
      foremilk (1 g/kg of BW), respectively, and the YH-1 and YH-2 groups were given
      daily administrations of YH (0.5 and 1 g/kg of BW, respectively). After 4 weeks,
      the YH-1, YH-2 and P-control groups showed significant differences in the body
      weight gain compared with the N-control group (p < 0.05). The YH-1 and YH-2
      groups also had significantly different tibial bone growths (0.47 and 0.49
      mm/day, respectively) and femur bone growths (0.52 and 0.53 mm/day, respectively)
      compared with the N-control group (0.37 mm/day of tibial growth and 0.42 mm/day
      of femur growth) (p < 0.05). The YH-1 and YH-2 groups had significantly different
      growth plate (proximal epiphysis) height increments (0.62 and 0.56 mm,
      respectively) compared with the N-control group (0.17 mm) (p < 0.05). Lastly, the
      YH-1 and YH-2 groups presented different growth hormone (GH) levels (1.77 and
      2.10 ng/mL, respectively) than the N-control group (0.82 ng/mL) (p < 0.05). YH
      administration increased longitudinal bone growth and GH secretion in rats.
      Consequently, YH may offer an improved ability to treat GH deficiency-related
      disorders.

PMID- 19107744
TI  - Ganoderma lucidum extract attenuates the proliferation of hepatic stellate cells
      by blocking the PDGF receptor.
AB  - Hepatic fibrosis is an outcome of chronic liver diseases. The activation and
      proliferation of hepatic stellate cells (HSCs) is a key event in liver injury.
      The fruiting body of Ganoderma lucidum has long been a popular oriental medicine
      for treating liver diseases. The aim of this present study was to investigate the
      antiproliferative effects of the triterpenoid-rich extract (GLT) of G. lucidum in
      a cell line of rat HSCs (HSC-T6) stimulated with platelet-derived growth factor
      (PDGF)-BB. DNA synthesis was investigated by bromodeoxyuridine (BrdU)
      incorporation. Flow cytometry using propidium iodide (PI) labeling was carried
      out to analyse the cell cycle distribution and apoptosis. alpha-Smooth muscle
      actin (alpha-SMA) was used to evaluate extracellular matrix deposition, and
      western blotting was performed to measure cyclins D1 and D2, and phosphorylation
      of the PDGFbeta-receptor (PDGFbetaR), Akt and JNK. The results indicated that the
      GLT attenuated BrdU incorporation in a concentration-dependent manner with an
      IC(50) of 8.52 +/- 0.33 microg/mL. The inhibitory effect of the GLT was
      associated with downregulation of cyclins D1 and D2, and PDGFbetaR and Akt
      phosphorylation, upregulation of JNK phosphorylation, and a reduction in alpha
      SMA expression. These results indicated that G. lucidum inhibits PDGF-BB
      activated HSC proliferation possibly through blocking PDGFbetaR phosphorylation,
      thereby indicating its efficacy for preventing and treating hepatic fibrosis.

PMID- 19107745
TI  - The effect of garlic consumption on Th1/Th2 cytokines in phytohemagglutinin (PHA)
      activated rat spleen lymphocytes.
AB  - The balance and regulation of T helper 1 (Th1) and Th2-type cytokines are
      important in the effective immune response to different diseases. To clarify the
      effect of garlic (Allium sativum L.) consumption on the Th1/Th2 balance, the
      secretion of gamma interferon (IFN-gamma) and interleukin-4 (IL-4), as two
      prototypes of Th1/Th2 cytokines, were compared in serum and supernatant of in
      vitro phytohemagglutinin activated rat spleen lymphocytes. Thirty male rats were
      divided equally into two groups. The treatment group received garlic solution in
      water (600 mg/kg/4 mL) and controls received distilled water by gavage. After 1
      month, serum and supernatant of PHA activated spleen lymphocytes were analysed
      for IFN-gamma and IL-4 by the enzyme-linked immunosorbent assay test and thymus
      and spleen weights were measured. The garlic treatment group showed significantly
      decreased production of IFN-gamma from 101.73 +/- 4.62 to 74.64 +/- 4.64 pg/mL
      and significantly increased IL-4 production from 26.75 +/- 3.35 to 83.92 +/- 6.56
      pg/mL (p < 0.001) in the supernatant of PHA induced spleen lymphocytes. The serum
      level of these cytokines was undetectable. The mean weight of thymuses in the
      garlic fed animals was significantly reduced from 0.456 +/- 0.016 to 0.368 +/-
      0.023 g compared with the control group (p < 0.005). There were no significant
      differences between the spleen weights in the two groups. In conclusion, oral
      garlic treatment may favor a Th2 or humoral immune response.

PMID- 19107746
TI  - Angiogenic effect of saponin extract from Panax notoginseng on HUVECs in vitro
      and zebrafish in vivo.
AB  - Angiogenesis plays an important role in a wide range of physiological processes
      such as wound healing and fetal development. In fact, many diseases are
      associated with imbalance in the regulation of angiogenesis in which there is
      either excessive or insufficient blood vessel formation. Panax notoginseng, a
      blood circulation invigorating herb, is commonly used in traditional Chinese
      medicine to treat circulation-related diseases. However, the biological effects
      of saponin extract from Panax notoginseng (PNS) on angiogenesis and the
      underlying mechanisms are yet to be fully elucidated. This investigation
      describes the angiogenic effects of PNS on human umbilical vein endothelial cells
      (HUVECs) in vitro and zebrafish in vivo. The 2,3-bis(2-methoxy-4-nitro-5
      sulfophenyl)5[(phenylamino)carbonyl]2H-tetrazolium hydroxide (XTT) assay and
      microscopic cell counting demonstrated that the extract was able to stimulate the
      proliferation of HUVECs. Meanwhile, the numbers of invaded cells and tube
      branches were significantly increased in PNS treatment groups. PNS was also shown
      to promote changes in the subintestinal vessels, a feature of angiogenesis, in
      zebrafish. In addition, by using real-time polymerase chain reaction (PCR), PNS
      was found to enhance vascular endothelial growth factor (VEGF) and kinase-domain
      region/fetal liver kinase-1 in mice (KDR/Flk-1) mRNA expression, and the PNS
      induced HUVECs proliferation could be abolished by a KDR/Flk-1 inhibitor.
      Furthermore, the proliferation of HUVECs induced by PNS was significantly
      attenuated by inhibitors of PI3K-Akt-eNOS. All the results suggest that PNS can
      promote angiogenesis, and that the proangiogenic effects involve the VEGF-KDR/Flk
      1 and PI3K-Akt-eNOS signaling pathways.

PMID- 19107747
TI  - Autoantibodies in autoimmune polyglandular syndrome type I patients react with
      major brain neurotransmitter systems.
AB  - Patients with autoimmune polyglandular syndrome type I (APS1) often display high
      titers of autoantibodies (autoAbs) directed against aromatic L-amino acid
      decarboxylase (AADC), tyrosine hydroxylase (TH), tryptophan hydroxylase (TPH),
      and glutamic acid decarboxylase (GAD). Neurological symptoms, including stiff-man
      syndrome and cerebellar ataxia, can occur in subjects with high levels of GAD
      autoAbs, particularly when patient sera can immunohistochemically stain gamma
      aminobutyric acid (GABA) neurons. However, it was not known if APS1 sera can also
      stain major monoamine systems in the brain. Therefore, in this work we applied
      sera from 17 APS1 patients known to contain autoAbs against AADC, TH, TPH, and/or
      GAD to rat brain sections and processed the sections according to the sensitive
      immunohistochemical tyramide signal amplification method. We found that autoAbs
      in sera from 11 patients were able to stain AADC-containing dopaminergic,
      serotonergic, and noradrenergic as well as AADC only (D-group) neurons and fibers
      in the rat brain, in several cases with a remarkably high quality and sensitivity
      (dilution up to 1:1,000,000); and, since they are human antibodies, they offer a
      good opportunity for performing multiple-labeling experiments using antibodies
      from other species. Six APS1 sera also stained GABAergic neuronal circuitries.
      Similar results were obtained in the mouse and primate brain. Our data
      demonstrate that many APS1 sera can immunostain the major monoamine and GABA
      systems in the brain. Only in a few cases, however, there was evidence that these
      autoAbs can be associated with neurological manifestations in APS1 patients, as,
      e.g., shown in previous studies in stiff-man syndrome.

PMID- 19107748
TI  - Regional brain activation changes and abnormal functional connectivity of the
      ventrolateral prefrontal cortex during working memory processing in adults with
      attention-deficit/hyperactivity disorder.
AB  - Previous studies on working memory (WM) function in adults with attention
      deficit/hyperactivity disorder (ADHD) suggested aberrant activation of the
      prefrontal cortex and the cerebellum. Although it has been hypothesized that
      activation differences in these regions most likely reflect aberrant
      frontocerebellar circuits, the functional coupling of these brain networks during
      cognitive performance has not been investigated so far. In this study, functional
      magnetic resonance imaging (fMRI) and both univariate and multivariate analytic
      techniques were used to investigate regional activation changes and functional
      connectivity differences during cognitive processing in healthy controls (n = 12)
      and ADHD adults (n = 12). Behavioral performance during a parametric verbal WM
      paradigm did not significantly differ between adults with ADHD and healthy
      controls. During the delay period of the activation task, however, ADHD patients
      showed significantly less activation in the left ventrolateral prefrontal cortex
      (VLPFC), as well as in cerebellar and occipital regions compared with healthy
      control subjects. In both groups, independent component analyses revealed a
      functional network comprising bilateral lateral prefrontal, striatal, and
      cingulate regions. ADHD adults had significantly lower connectivity in the
      bilateral VLPFC, the anterior cingulate cortex, the superior parietal lobule, and
      the cerebellum compared with healthy controls. Increased connectivity in ADHD
      adults was found in right prefrontal regions, the left dorsal cingulate cortex
      and the left cuneus. These findings suggest both regional brain activation
      deficits and functional connectivity changes of the VLPFC and the cerebellum as
      well as functional connectivity abnormalities of the anterior cingulate and the
      parietal cortex in ADHD adults during WM processing.

PMID- 19107749
TI  - Functional brain imaging of swallowing: an activation likelihood estimation meta
      analysis.
AB  - A quantitative, voxel-wise meta-analysis was performed to investigate the
      cortical control of water and saliva swallowing. Studies that were included in
      the meta-analysis (1) examined water swallowing, saliva swallowing, or both, and
      (2) reported brain activation as coordinates in standard space. Using these
      criteria, a systematic literature search identified seven studies that examined
      water swallowing and five studies of saliva swallowing. An activation likelihood
      estimation (ALE) meta-analysis of these studies was performed with GingerALE. For
      water swallowing, clusters with high activation likelihood were found in the
      bilateral sensorimotor cortex, right inferior parietal lobule, and right anterior
      insula. For saliva swallowing, clusters with high activation likelihood were
      found in the left sensorimotor cortex, right motor cortex, and bilateral
      cingulate gyrus. A between-condition meta-analysis revealed clusters with higher
      activation likelihood for water than for saliva swallowing in the right inferior
      parietal lobule, right postcentral gyrus, and right anterior insula. Clusters
      with higher activation likelihood for saliva than for water swallowing were found
      in the bilateral supplementary motor area, bilateral anterior cingulate gyrus,
      and bilateral precentral gyrus. This meta-analysis emphasizes the distributed and
      partly overlapping cortical networks involved in the control of water and saliva
      swallowing. Water swallowing is associated with right inferior parietal
      activation, likely reflecting the sensory processing of intraoral water
      stimulation. Saliva swallowing more strongly involves premotor areas, which are
      crucial for the initiation and control of movements.

PMID- 19107750
TI  - Linearity of the fMRI response in category-selective regions of human visual
      cortex.
AB  - The goal of this study was to determine the linearity of the blood oxygen level
      dependent (BOLD) response, as measured by functional magnetic resonance imaging
      (fMRI), in category-selective regions of human visual cortex. We defined regions
      of the temporal lobe that were selective to faces (fusiform face area, FFA) and
      places (parahippocampal place area, PPA). We then determined the linearity of the
      BOLD response in these regions to their preferred and nonpreferred stimuli.
      First, we tested the principle of scaling. As we increased the visibility of the
      stimulus, there was a corresponding linear increase in the fMRI signal in the FFA
      and PPA to their preferred stimulus (face and place, respectively). In contrast,
      responses in the FFA and PPA to the nonpreferred stimulus did not conform to the
      principle of scaling. Next, we asked whether the fMRI response in these regions
      of visual cortex conformed to the principle of additivity. To assess this, we
      determined whether the response to a long stimulus block could be predicted by
      adding the response to multiple shorter duration blocks. Although the fMRI
      response in the FFA and PPA was generally linear to the preferred stimulus, a
      more nonlinear response was apparent to the nonpreferred stimulus. In conclusion,
      the linearity of the BOLD response in the human ventral visual pathway varied
      across cortical region and stimulus category. This suggests that measures of
      linearity may provide a useful indication of neural selectivity in the brain.

PMID- 19107751
TI  - Extraction of situational meaning by integrating multiple meanings in a complex
      environment: a functional MRI study.
AB  - Humans extract behaviorally significant meaning from a situation by integrating
      meanings from multiple components of a complex daily environment. To determine
      the neural underpinnings of this ability, the authors performed functional
      magnetic resonance imaging of healthy subjects while the latter viewed
      naturalistic scenes of two people and an object, including a threatening
      situation of a person being attacked by an offender with an object. The authors
      used a two-factorial design: the object was either aversive or nonaversive, and
      the offender's action was either directed to the person or elsewhere. This
      allowed the authors to examine the neural response to object aversiveness and
      person-directed intention separately. A task unrelated to threat was also used to
      address incidental (i.e., subconscious or unintentional) detection. Assuming
      individual differences in incidental threat detection, the authors used a
      functional connectivity analysis using principal components analysis of
      intersubject variability. The left lateral orbitofrontal cortex and medial
      prefrontal cortex (MPFC) were specifically activated in response to a threatening
      situation. The threat-related component of intersubject variability was extracted
      from these data and showed a significant correlation with personality scores.
      There was also a correlation between threat-related intersubject variability and
      activation for object aversiveness in the left temporal pole and lateral
      orbitofrontal cortex; person-directed intention in the left superior frontal
      gyrus; threatening situations in the left MPFC; and independently for both
      factors in the right MPFC. Results demonstrate independent processing of object
      aversiveness and person-directed intention in the left temporal-orbitofrontal and
      superior frontal networks, respectively, and their integration into situational
      meaning in the MPFC.

PMID- 19107752
TI  - White-matter abnormalities in attention deficit hyperactivity disorder: a
      diffusion tensor imaging study.
AB  - Current evidence suggests that attention deficit hyperactivity disorder (ADHD)
      involves dysfunction in wide functional networks of brain areas associated with
      attention and cognition. This study examines the structural integrity of white
      matter neural pathways, which underpin these functional networks, connecting
      fronto-striatal and fronto-parietal circuits, in children with ADHD. Fifteen
      right-handed 8 to 18-year-old males with ADHD-combined type and 15 right-handed,
      age, verbal, and performance IQ-matched, healthy males underwent diffusion tensor
      imaging. A recent method of tract-based spatial statistics was used to examine
      fractional anisotropy (FA) and mean diffusivity within major white-matter
      pathways throughout the whole-brain. White-matter abnormalities were found in
      several distinct clusters within left fronto-temporal regions and right parietal
      occipital regions. Specifically, participants with ADHD showed greater FA in
      white-matter regions underlying inferior parietal, occipito-parietal, inferior
      frontal, and inferior temporal cortex. Secondly, eigenvalue analysis suggests
      that the difference in FA in ADHD may relate to a lesser degree of neural
      branching within key white-matter pathways. Tractography methods showed these
      regions to generally form part of white-matter pathways connecting prefrontal and
      parieto-occipital areas with the striatum and the cerebellum. Our findings
      demonstrate anomalous white-matter development in ADHD in distinct cortical
      regions that have previously been shown to be dysfunctional or hypoactive in fMRI
      studies of ADHD. These data add to an emerging picture of abnormal development
      within fronto-parietal cortical networks that may underpin the cognitive and
      attentional disturbances associated with ADHD.

PMID- 19107753
TI  - Model driven EEG/fMRI fusion of brain oscillations.
AB  - This article reviews progress and challenges in model driven EEG/fMRI fusion with
      a focus on brain oscillations. Fusion is the combination of both imaging
      modalities based on a cascade of forward models from ensemble of post-synaptic
      potentials (ePSP) to net primary current densities (nPCD) to EEG; and from ePSP
      to vasomotor feed forward signal (VFFSS) to BOLD. In absence of a model, data
      driven fusion creates maps of correlations between EEG and BOLD or between
      estimates of nPCD and VFFS. A consistent finding has been that of positive
      correlations between EEG alpha power and BOLD in both frontal cortices and
      thalamus and of negative ones for the occipital region. For model driven fusion
      we formulate a neural mass EEG/fMRI model coupled to a metabolic hemodynamic
      model. For exploratory simulations we show that the Local Linearization (LL)
      method for integrating stochastic differential equations is appropriate for
      highly nonlinear dynamics. It has been successfully applied to small and medium
      sized networks, reproducing the described EEG/BOLD correlations. A new LL
      algebraic method allows simulations with hundreds of thousands of neural
      populations, with connectivities and conduction delays estimated from diffusion
      weighted MRI. For parameter and state estimation, Kalman filtering combined with
      the LL method estimates the innovations or prediction errors. From these the
      likelihood of models given data are obtained. The LL-innovation estimation method
      has been already applied to small and medium scale models. With improved Bayesian
      computations the practical estimation of very large scale EEG/fMRI models shall
      soon be possible.

PMID- 19107754
TI  - Neural basis of individualistic and collectivistic views of self.
AB  - Individualism and collectivism refer to cultural values that influence how people
      construe themselves and their relation to the world. Individualists perceive
      themselves as stable entities, autonomous from other people and their
      environment, while collectivists view themselves as dynamic entities, continually
      defined by their social context and relationships. Despite rich understanding of
      how individualism and collectivism influence social cognition at a behavioral
      level, little is known about how these cultural values modulate neural
      representations underlying social cognition. Using cross-cultural functional
      magnetic resonance imaging (fMRI), we examined whether the cultural values of
      individualism and collectivism modulate neural activity within medial prefrontal
      cortex (MPFC) during processing of general and contextual self judgments. Here,
      we show that neural activity within the anterior rostral portion of the MPFC
      during processing of general and contextual self judgments positively predicts
      how individualistic or collectivistic a person is across cultures. These results
      reveal two kinds of neural representations of self (eg, a general self and a
      contextual self) within MPFC and demonstrate how cultural values of individualism
      and collectivism shape these neural representations.

PMID- 19107755
TI  - Is a preserved functional reserve a mechanism limiting clinical impairment in
      pediatric MS patients?
AB  - We evaluated the functional magnetic resonance imaging (fMRI) correlates of
      simple movement performance in patients with pediatric multiple sclerosis (MS)
      and their relation with the extent of T2 lesion volume (LV), to improve our
      understanding of the mechanisms leading to their short/medium term favorable
      clinical course. We obtained fMRI during repetitive flexion-extension of the last
      four fingers of the right hand and brain dual-echo scans from 17 right-handed
      patients with pediatric relapsing-remitting MS and 9 sex- and age-matched right
      handed healthy controls. T2 LV was measured using a local thresholding
      segmentation technique. fMRI activations and functional connectivity analysis
      were performed using SPM2. Compared to controls, pediatric MS patients had an
      increased recruitment of the left (L) primary sensorimotor cortex (SMC). They
      also showed reduced functional connectivity between the L primary SMC and the L
      thalamus (P = 0.03), the L insula and the L secondary sensorimotor cortex (SII)
      (P = 0.02), the supplementary motor area and the L SII (P = 0.02), the L thalamus
      and the L insula (P = 0.01) and the L thalamus and the L SII (P = 0.003). In
      patients with pediatric MS, the activity of the L primary SMC was significantly
      correlated with brain T2 LV (r = 0.78). No correlation was found between
      coefficients of abnormal connectivity and structural MRI measures. The
      maintenance of a selective and strictly lateralized pattern of movement
      associated brain activations and a modulation of its functional connections
      suggest a preserved functional reserve in patients with pediatric MS, which, in
      turn, might contribute to explain their favorable clinical evolution at
      short/medium term.

PMID- 19107757
TI  - Inhibition of peroxidase-catalyzed iodination by cephalosporins: Metallo-beta
      lactamase-induced antithyroid activity of antibiotics.
AB  - Broad-spectrum antibiotics with heterocyclic side chains strongly inhibit
      peroxidase-catalyzed iodination in the presence of metallo-beta-lactamase. This
      suggests that antibiotic resistance due to hydrolysis of the beta-lactam ring in
      antibiotics would have negative effects on thyroid activity.

PMID- 19107756
TI  - Expression of the regeneration-associated protein SPRR1A in primary sensory
      neurons and spinal cord of the adult mouse following peripheral and central
      injury.
AB  - Small proline-rich repeat protein 1A (SPRR1A) is expressed in dorsal root
      ganglion (DRG) neurons following peripheral nerve injury but it is not known
      whether SPRR1A is differentially expressed following injury to peripheral versus
      central DRG projections and a detailed characterization of expression in sensory
      neuron subpopulations and spinal cord has not been performed. Here we use
      immunocytochemical techniques to characterize SPRR1A expression following sciatic
      nerve, dorsal root, and dorsal column injury in adult mice. SPRR1A was not
      detected in naive spinal cord, DRG, or peripheral nerves and there was minimal
      expression following injury to the centrally projecting branches of DRG neurons.
      However, following peripheral (sciatic) nerve injury, intense SPRR1A
      immunoreactivity was observed in the dorsal horn and motoneurons of the spinal
      cord, in L4/5 DRG neurons, and in the injured nerve. A time-course study
      comparing expression following sciatic nerve crush and transection revealed
      maximum SPRR1A levels at day 7 in both models. However, while SPRR1A was
      downregulated to baseline by 30 days postlesion following crush injury, it
      remained elevated 30 days after transection. Cell-size and double-labeling
      studies revealed that SPRR1A was expressed by DRG cells of all sizes and
      colocalized with classical markers of DRG subpopulations and their primary
      afferent terminals. High coexpression of SPRR1A with activating transcription
      factor-3 and growth-associated protein-43 was observed, indicating that it is
      expressed by injured and regenerating neurons. This study supports the hypothesis
      that SPRR1A is a regeneration-associated gene and that SPRR1A provides a valuable
      marker to assess the regenerative potential of injured neurons.

PMID- 19107758
TI  - Exploring kinase cosubstrate promiscuity: monitoring kinase activity through
      dansylation.

PMID- 19107759
TI  - Single-molecule FRET reveals structural heterogeneity of SDS-bound alpha
      synuclein.
AB  - SDS-concentration-dependent alpha-synuclein structure: Upon interaction with SDS,
      alpha Syn folds into a structure with two antiparallel alpha-helices. We show
      from single-molecule FRET that alpha Synn adopts this conformation in an all-or
      none fashion below the SDS critical micelle concentration. Population of the
      folded species is directly coupled to an increase in alpha-helix content; this
      suggests that the entire N terminus is involved in the transaction.

PMID- 19107760
TI  - Structurally minimized mu-conotoxin analogues as sodium channel blockers:
      implications for designing conopeptide-based therapeutics.
AB  - Disulfide bridges that stabilize the native conformation of conotoxins pose a
      challenge in the synthesis of smaller conotoxin analogues. Herein we describe the
      synthesis of a minimized analogue of the analgesic mu-conotoxin KIIIA that blocks
      two sodium channel subtypes, the neuronal Na(V)1.2 and skeletal muscle Na(V)1.4.
      Three disulfide-deficient analogues of KIIIA were initially synthesized in which
      the native disulfide bridge formed between either C1-C9, C2-C15, or C4-C16 was
      removed. Deletion of the first bridge only slightly affected the peptide's
      bioactivity. To further minimize this analogue, the N-terminal residue was
      removed and two nonessential serine residues were replaced by a single 5-amino-3
      oxapentanoic acid residue. The resulting "polytide" analogue retained the ability
      to block sodium channels and to produce analgesia. Until now, the peptidomimetic
      approach applied to conotoxins has progressed only modestly at best; thus, the
      disulfide-deficient analogues containing backbone spacers provide an alternative
      advance toward the development of conopeptide-based therapeutics.

PMID- 19107762
TI  - Genetic susceptibility of lung cancer associated with common variants in the 3'
      untranslated regions of the adenosine triphosphate-binding cassette B1 (ABCB1)
      and ABCC1 candidate transporter genes for carcinogen export.
AB  - BACKGROUND: Tobacco-specific nitrosamine 4-(methylnitrosamino)-1-(3-pyridyl)-1
      butanone (NKK) is a well defined carcinogen that can induce lung cancer. Genetic
      polymorphisms in its disposition pathways could modify the risk of developing
      lung cancer. The authors of this report previously catalogued the sequence
      variations of the adenosine triphosphate-binding cassette B1 (ABCB1) and ABCC1
      candidate transporter genes for carcinogen export in the Chinese population and
      screened out common variants with potential function in their 5' flanking and 3'
      untranslated regions. The objective of the current study was to test the
      hypothesis that these common variants are associated with lung cancer risk.
      METHODS: The genotyping analyses for 6 common regulatory variants (reference
      single-nucleotide polymorphism 4728709 [rs4728709] and rs2188524 in the 5'
      flanking region of ABCB1 and rs3842 in its 3' untranslated region; rs3743527,
      rs212090, and rs212091 in the 3' untranslated region of ABCC1) was conducted in a
      case-control study of 500 patients with incident lung cancer and 517 cancer-free
      controls in a Chinese population. RESULTS: Compared with the wild
      adenosine/adenosine (A/A) genotype, the variant rs3842 genotype
      (adenosine/guanosine [A/G] + G/G) of ABCB1 was associated with a statistically
      significant increased risk of developing lung cancer (odds ratio [OR]. 1.36; 95%
      confidence interval [95% CI], 1.06-1.76). Also evident was the association
      between cancer susceptibility and the variant rs212090 genotype
      (adenosine/thymidine [A/T] + T/T) of ABCC1 (OR, 1.37; 95% CI, 1.03-1.83).
      Haplotype-based association analysis also emphasized that 2 common haplotypes
      carrying the culprit alleles of the 2 single-nucleotide polymorphisms were
      associated with an increased risk of cancer. In addition, stratification analysis
      demonstrated a remarkable association of ABCB1 rs3842 with the risk of cancer
      manifested in women (OR, 2.57; 95% CI, 1.36-4.85), in the histologic type of
      adenocarcinoma (OR, 1.42; 95% CI, 1.03-1.99), and in individuals aged <60 years
      (OR, 1.50; 95% CI, 1.05-2.14). CONCLUSIONS: The current study demonstrated that
      common polymorphisms in the 3' untranslated region of ABCB1 and ABCC1 may
      contribute to the etiology of lung cancer, providing further support for the
      hypothesis that genetic components in the metabolism and the disposition of NNK
      may modify the risk of lung cancer, especially in lung adenocarcinoma among
      women. Functional studies are warranted to elucidate whether aberrant expression
      and dysfunction of ABC transporters for carcinogen export may play a role in the
      development of lung cancer.

PMID- 19107761
TI  - Race, treatment preferences, and hospice enrollment: eligibility criteria may
      exclude patients with the greatest needs for care.
AB  - BACKGROUND: The requirement that patients give up curative treatment makes
      hospice enrollment unappealing for some patients and may particularly limit use
      among African-American patients. The current study was conducted to determine
      whether African-American patients with cancer are more likely than white patients
      to have preferences for cancer treatment that exclude them from hospice and
      whether they are less likely to want specific hospice services. METHODS: Two
      hundred eighty-three patients who were receiving treatment for cancer at 6
      oncology clinics within the University of Pennsylvania Cancer Network completed
      conjoint interviews measuring their perceived need for 5 hospice services and
      their preferences for continuing cancer treatment. Patients were followed for 6
      months or until death. RESULTS: African-American patients had stronger
      preferences for continuing their cancer treatments on a 7-point scale even after
      adjusting for age, sex, finances, education, Eastern Cooperative Oncology Group
      performance status, quality of life, and physical and psychologic symptom burden
      (adjusted mean score, 4.75 vs 3.96; beta coefficient, 0.82; 95% confidence
      interval, 0.22-1.41 [P = .007]). African-American patients also had greater
      perceived needs for hospice services after adjusting for these characteristics
      (adjusted mean score, 2.31 vs 1.83; beta coefficient, 0.51; 95% confidence
      interval, 0.11-0.92 [P = .01]). However, this effect disappeared after adjusting
      for household finances. CONCLUSIONS: Hospice eligibility criteria may exclude
      African-American patients disproportionately despite greater perceived needs for
      hospice services in this population. The mechanisms driving this health disparity
      likely include both cultural differences and economic characteristics, and
      consideration should be given to redesigning hospice eligibility criteria.

PMID- 19107763
TI  - Phase 2 open-label study of single-agent sorafenib in treating advanced
      hepatocellular carcinoma in a hepatitis B-endemic Asian population: presence of
      lung metastasis predicts poor response.
AB  - BACKGROUND: The current study was a phase 2 open-label study to evaluate the
      efficacy and tolerability of single-agent sorafenib in the treatment of advanced
      HCC patients in a hepatitis B-endemic Asian population. METHODS: Patients with
      advanced hepatocellular carcinoma (HCC) received sorafenib at a dose of 400 mg
      twice daily in 4-week cycles. Tumor response was assessed every 3 cycles using
      Response Evaluation Criteria in Solid Tumors criteria. RESULTS: Fifty-one
      patients were enrolled in the study and were treated with sorafenib for at least
      12 weeks. The median age was 56 years (range, 28-79 years). Approximately 90% had
      hepatitis B virus-related HCC. Thirty-six (71%) patients had underlying Child
      Pugh A cirrhosis, 13 (26%) Child-Pugh B, and 2 (3%) Child-Pugh C. Four (8%)
      patients achieved partial responses, and 9 (18%) patients had stable disease for
      at least 12 weeks. The median overall survival was 5 months (range, 4-17 months).
      Patients without extrahepatic spread, particularly without lung metastasis
      (P<.01), are more likely to benefit from sorafenib treatment. The most common
      toxicities were diarrhea (67%), malaise (55%), and hand-foot-skin reaction (54%).
      The majority of patients had transient liver function derangement. Patients with
      and without underlying portal vein thrombosis had similar therapeutic benefits
      and likewise shared a similar treatment-related toxicity profile with sorafenib
      treatment. CONCLUSIONS: Single-agent sorafenib demonstrates good efficacy and
      acceptable tolerability in treating an advanced HCC patient population in a
      hepatitis B-endemic area. The presence of lung metastasis predicts poor response
      to sorafenib in advanced HCC patients.

PMID- 19107764
TI  - Absolute metabolite concentrations calibrated using the total water signal in
      brain (1)H MRS.
AB  - Magnetic resonance spectroscopy (MRS) has been coupled with a multi-echo imaging
      sequence to determine the relaxation corrected signal areas of the metabolites
      and the tissue water. Stimulated echo acquisition mode (STEAM) spectra (TE/TM/TR
      30/13.7/5000 ms) acquired from gray and white matter voxels in 43 healthy
      volunteers were fit using LCModel. Corresponding water signals, measured using a
      multi-echo T(2) imaging sequence, were fit with a Non-Negative Least Squares
      algorithm. Using this approach the water area could be T(1) and T(2) corrected
      for all three water compartments: cerebrospinal fluid (CSF), intra- and extra
      cellular water, and myelin water. The image-based water measurement is an
      improvement over spectroscopy methods because it can be more sensitive to water
      changes in diseased tissue. Metabolite areas were also corrected for relaxation
      losses. In occipital gray matter, the concentrations of Cho, Cr, and N-acetyl
      aspartate (NAA) were 1.27 (0.06), 8.9 (0.3), and 9.3 (0.3) mmol/L tissue,
      respectively and in parietal white matter they were 1.90 (0.05), 7.9 (0.2), and
      9.8 (0.2) mmol/L tissue. The Cho and Cr concentrations were different in
      occipital gray compared to parietal white matter (p < 0.0001 and <0.005,
      respectively).

PMID- 19107765
TI  - Selectivity differences between alkyl and polar-modified alkyl phases in reversed
      phase high performance liquid chromatography.
AB  - Compared to conventional C18 phases, polar-modified phases have distinct
      differences with regards to chromatographic behavior. In the present study, ODS
      phases and polar-modified phases were synthesized. The columns containing these
      new packings demonstrated satisfactory stability under both acidic (pH 1.5) and
      basic (pH 10) conditions. We evaluated the selectivity differences between alkyl
      and polar-modified alkyl RP columns by using a range of neutral analytes. The
      polar-modified alkyl phases showed excellent peak shapes for almost all
      compounds. We also compared the selectivity differences between them for
      separating nucleotides by using 100% aqueous mobile phase and tricyclic
      antidepressants in the intermediate pH mobile phases. The results demonstrated
      that polar-modified phases display a significantly reduced hydrophobic nature and
      a significantly reduced silanol activity compared to the conventional C18 phases.

PMID- 19107766
TI  - Simultaneous determination of pyrethroids from pesticide residues in porcine
      muscle and pasteurized milk using GC.
AB  - The principal goal of this work was to develop an efficient method for the
      simultaneous determination of four pyrethroid (PYR) insecticides, cyfluthrin,
      cyhalothrin, cypermethrin, and deltamethrin, in porcine muscle and pasteurized
      milk using liquid-liquid extraction (LLE). Sample extraction was carried out with
      and without additional column cleanup procedures, and the final determination was
      made using GC with electron-capture detector (ECD). The pesticide identity was
      confirmed using GC-MS in the SIM mode. Since there were minor differences between
      the extraction procedures, extraction without the additional cleanup procedure
      was used throughout the work. The method was validated by fortifying blank
      samples with half, two, and four times the maximum residue limit (MRL) of each
      PYR. The average recoveries (n = 6) ranged from 83.5 to 99.2% and 82.9 to 109% in
      porcine muscle and pasteurized milk, respectively. The repeatability of
      measurements expressed as RSDs, was in the range of 1.7-11.9 and 1.5-10.3% in
      porcine muscle and pasteurized milk, respectively. The LODs ranged from 3.3 to 9
      and 3 to 8.1 ppm, whereas the LOQs ranged from 10 to 27.4 and 9 to 24.6 ppm, in
      porcine muscle and pasteurized milk, respectively. The applicability of the
      method was demonstrated by analyzing real samples collected from major cities in
      the Republic of Korea. No residues of the selected pesticides were detected in
      any of the samples.

PMID- 19107767
TI  - Determination of main taxoids in Taxus species by microwave-assisted extraction
      combined with LC-MS/MS analysis.
AB  - A method based on microwave-assisted extraction (MAE) has been developed for the
      determination of paclitaxel and five related taxoids, namely 10-deacetylbaccatin
      III (10-DAB III), cephalomannine, 10-deacetylpaclitaxel (10-DAT), 7-xyl-10-
      deacetylpaclitaxel (7-xyl-10-DAT), and 7-epi-10-deacetylpaclitaxel (7-epi-10-DAT)
      in Taxus species in this study. The influential parameters of the MAE procedure
      were optimized, and the optimal conditions were as follows: extraction solvent
      80% ethanol solution, solid/liquid ratio 1:10 (g/mL), temperature 50 degrees C,
      and three extraction cycles, each cycle 10 min. The method validation for LC
      MS/MS analysis was performed. The LOD and LOQ were 3.16-9.20 and 12.20-30.45
      ng/mL, respectively. Repeatability and reproducibility for the six taxiods with
      RSD ranged from 2.78 to 3.85% and from 5.26 to 6.60%. The recoveries of the
      method for the six taxoids were 92.6-105.6%. The developed MAE-LC-MS/MS method
      was also successfully applied to determine the contents of six taxoids in
      different Taxus species.

PMID- 19107768
TI  - Symptom distress, interventions, and outcomes of intensive care unit cancer
      patients referred to a palliative care consult team.
AB  - BACKGROUND: The symptom burden of intensive care unit (ICU) patients who are
      referred to a palliative care team (PCT) has not been characterized to the
      authors' knowledge, and the response of these symptoms to the palliative care
      intervention has not been reported. METHODS: The authors retrospectively reviewed
      PCT consults for ICU patients who were seen between July 2006 and October 2007.
      To characterize symptom distress and outcomes in ICU patients who were referred
      to PCT in a cancer center, information and descriptive statistics about patients'
      demographics, comorbidities, PCT findings, interventions, and outcomes were
      obtained. The chi-square test was used to analyze ICU and PCT mortality, and the
      signed-rank test was used to analyze PCT interventions. RESULTS: Of 1637 PCT
      consults, 88 consults (5%) were from the ICU. The median patient age was 60 years
      (range, 22-87 years), and 41 patients (46%) were women. The types of cancers were
      hematologic (19 patients; 22%), gastrointestinal (19 patients; 22%), lung (18
      patients; 20%), and others (24 patients; 26%). Nineteen patients were on
      mechanical ventilation (MV), and 24 patients were on bilevel positive airway
      pressure (BIPAP). The findings were delirium (71 patients; 81%), dyspnea (67
      patients; 76%), pain (74 patients; 84%), fatigue (84 patients; 95%), and anxiety
      (57 patients; 65%). The interventions used were opioid management (99%), steroids
      (70%), antipsychotics (76%), and counseling (100%), do not resuscitate conversion
      (62 of 88 patients; 70%), withdrawal of MV (15 of 19 patients; 79%), and
      withdrawal of BIPAP (26 of 26 patients; 100%). Improvement was reported in pain
      (67 patients; 90%), dyspnea (60 patients; 90%), anxiety (51 patients; 80%), and
      delirium (31 patients; 44%). Thirty-five patients (40%) were transferred to the
      palliative care unit (PCU). Fifty-one ICU/PCT patients (58%) died during
      admission versus 130 of 1549 (8%) non-ICU PCT patients (P<.0001). Twenty-three of
      35 patients who were transferred to the PCU (66%) died there versus 212 of 629
      patients (34%) who were admitted to the PCU from another service (P<.0001).
      Thirty-seven of 88 ICU/PCT patients (42%) were discharged alive. CONCLUSIONS: ICU
      patients who are referred to the PCT have severe symptom distress. The PCT was
      able to identify multiple problems and make numerous pharmacologic and
      nonpharmacologic recommendations that improved these symptoms, including the
      participation in do not resuscitate conversion and withdrawal of MV and BIPAP.
      Although many patients in this population died, a significant subset, including
      those who were transferred to the PCU, survived to discharge.

PMID- 19107769
TI  - Do phase 1 patients have greater needs for palliative care compared with other
      cancer patients?
AB  - BACKGROUND: Phase 1 oncology trial participants often are excluded from hospice.
      However, it is not known whether they would benefit from hospice services. The
      objectives of the current study were to define the palliative care needs of these
      patients and to determine whether their needs are greater than those of other
      cancer patients. METHODS: Two hundred ninety-seven patients who were undergoing
      cancer therapy and 69 patients who were enrolled in phase 1 trials at 7 oncology
      clinics in an urban cancer network were recruited and consented to participate in
      interviews. Interviewers assessed the prevalence and severity of 10 symptoms
      using the Global Distress Index of the Memorial Symptom Assessment Scale and
      patients' perceived need for 4 services typically provided through hospice: a
      chaplain, counselor, home health aide, and visiting nurse. RESULTS: Patients in
      the 2 groups had a similar symptom burden. However, after adjusting for Eastern
      Cooperative Oncology Group performance status scores, phase 1 patients were more
      likely to have 5 of the 10 symptoms and reported greater severity for 6 of the 10
      symptoms. Compared with other patients, phase 1 patients were less likely to say
      they needed a home health aide (4 of 69 patients [6%] vs 198 of 297 patients
      [67%]), a chaplain (7 of 69 patients [10%] vs 134 of 297 patients [45%]), or a
      counselor (11 of 69 patients [16%] vs 160 of 297 patients [54%]; chi-square test:
      P<.001 for all). They were equally likely to say they needed a visiting nurse (30
      of 69 patients [44%] vs 142 of 297 patients [48%]; chi-square test: P=.516).
      CONCLUSIONS: Compared with other patients who had cancer, patients who were
      participating in phase 1 trials were less likely to want several home care
      services, although they experienced a greater symptom burden. Further research
      will be needed to define the palliative care needs of this population.

PMID- 19107770
TI  - Defining a molecular phenotype for benign and malignant parathyroid tumors.
AB  - BACKGROUND: It is frequently difficult to establish histologically whether a
      parathyroid tumor is a parathyroid carcinoma, parathyromatosis, or an atypical
      adenoma. The authors asked whether these tumors have a distinctive molecular
      profile, whether benign tumors could be distinguished from malignant tumors, and
      whether parathyromatosis is a low-grade parathyroid carcinoma or is benign tissue
      that can invade other organs. METHODS: Samples of parathyroid carcinoma, atypical
      adenoma, parathyromatosis, parathyroid adenoma, and hyperplasia were obtained for
      tissue microarray studies. The molecular expression of genes involved in
      parathyroid tumor progression (HRPT2 ["parafibromin"], galectin-3, Ki-67, Rb,
      p27, and mdm-2) was investigated by immunohistochemistry. RESULTS: Complete loss
      of parafibromin expression was seen in 5 of 16 (31.3%) parathyroid carcinomas;
      all parathyromatosis, atypical adenomas, adenomas, and hyperplasia stained
      positive for parafibromin. Loss of Rb expression was seen in 5 (33.3%) of 15
      parathyroid carcinomas and 1 (7.1%) of 14 parathyroid hyperplasias; all
      parathyromatosis, atypical adenomas, and adenomas stained positive. Galectin-3
      stained strongly positive in 14 (93.3%) of 15 parathyroid carcinomas, and
      positive in 3 (18.7%) of 16 cases of parathyromatosis, 2 (100%) of 2 atypical
      adenomas, 1 (5.6%) of 18 adenomas, and 2 (14.3%) of 14 hyperplasias. The Ki-67
      proliferative index was high in 9 (60%) of 15 parathyroid carcinomas, 1 (6.7%) of
      15 cases of parathyromatosis, 1 (5.6%) of 18 adenomas, and no atypical adenomas
      or hyperplasia. P27 and mdm-2 protein expression did not differ appreciably among
      the tumor types. CONCLUSIONS: No single diagnostic marker currently determines
      whether a parathyroid tumor is a parathyroid carcinoma, but loss of parafibromin
      and Rb expression, and overexpression of galectin-3, generally distinguish
      parathyroid carcinoma from other parathyroid tumors. Parathyromatosis does not
      appear to be a low-grade parathyroid carcinoma.

PMID- 19107771
TI  - Patients' attitudes to medicines and adherence to maintenance treatment in
      inflammatory bowel disease.
AB  - BACKGROUND: Nonadherence has been reported in over 40% of patients taking
      maintenance therapies (MT) for inflammatory bowel disease (IBD). Studies in other
      illness groups have shown that nonadherence is related to negative attitudes to
      treatment. The aim of this study was to assess patients' attitudes to MT for IBD
      (beliefs about personal need for MT and potential adverse effects) and to
      identify whether such beliefs are associated with adherence to MT. METHODS: A
      cross-sectional survey was conducted in which 1871 members of the National
      Association for Colitis and Crohn's Disease (NACC) completed validated
      questionnaires assessing beliefs about MT and adherence to MT. RESULTS: Low
      adherence to MT was reported by 29% of participants and was associated with
      doubts about personal need for MT (odds ratio [OR] = 0.56; 95% confidence
      interval [CI]: 0.48-0.64; P < 0.001) and concerns about potential adverse effects
      (OR = 1.66; 95% CI: 1.42-1.94; P < 0.001). Attitudinal analysis showed that while
      almost half (48%) of the participants were "accepting" of MT (high necessity, low
      concerns), a large proportion of the sample (42%) were "ambivalent" about MT
      (high necessity, high concerns), 6% were "sceptical" (low necessity, high
      concerns) and 4% were "indifferent" (low necessity, low concerns). Compared to
      those who were "accepting" of MT, participants in all 3 other attitudinal groups
      were significantly more likely to be nonadherent. CONCLUSIONS: The way in which
      patients judge their personal need for MT relative to their concerns about MT can
      be a significant barrier to adherence. Interventions to facilitate optimal
      adherence to MT for IBD should address such perceptual barriers.

PMID- 19107772
TI  - Human neutrophil peptides 1-3 are useful biomarkers in patients with active
      ulcerative colitis.
AB  - BACKGROUND: A specific useful biomarker for diagnosing ulcerative colitis (UC)
      has not yet been described. This study employed proteomics to identify serum
      protein biomarkers for UC. METHODS: Ninety-four blood samples were isolated from
      patients and controls (including 48 UC, 22 Crohn's disease [CD], 5 colorectal
      cancer, and 6 infectious colitis patients and 13 healthy subjects). Serum samples
      were analyzed using the SELDI-TOF/MS ProteinChip system. After applying the
      samples to ProteinChip arrays, we assessed differences in the proteomes using
      Ciphergen ProteinChip software and identified candidate proteins, which were then
      characterized in immunoassays. RESULTS: Preliminary analysis using the
      ProteinChip system revealed significant peak-intensity differences for 27 serum
      proteins between 11 patients with UC and 7 healthy subjects. Among these
      proteins, 3 proteins (with mass/charge ratios of approximately 3400) were
      identified as human neutrophil peptides 1-3 (HNP 1-3). The presence of HNP 1-3 in
      the patient sera was confirmed using immunoassays. Enzyme-linked immunosorbent
      assays demonstrated that the mean plasma concentration of HNP 1-3 was
      significantly higher in patients with active UC (n = 28) than in patients whose
      UC was in remission (n = 20) or patients with CD (n = 22), infectious colitis, or
      healthy subjects, and tended to be higher than in patients with colon cancer. In
      addition, the plasma concentration of HNP 1-3 in patients that responded to
      corticosteroids-based therapy decreased after treatment, whereas it was not
      changed in nonresponders. CONCLUSIONS: HNP 1-3 is a novel biomarker that may be
      useful for diagnosing patients with active UC and predicting treatment outcomes.

PMID- 19107773
TI  - Is chronic pain an extraintestinal manifestation of IBD?

PMID- 19107774
TI  - Acute hemorrhagic Crohn's disease controlled with infliximab.

PMID- 19107775
TI  - Crohn's disease and radiation exposure: it's time we got our act together?

PMID- 19107776
TI  - A lump of coal for perianal fistulae?

PMID- 19107778
TI  - Large-volume late-onset pelvic fluid collection after ileal pouch-anal
      anastomosis.

PMID- 19107777
TI  - Age of diagnosis influences serologic responses in children with Crohn's disease:
      a possible clue to etiology?
AB  - BACKGROUND: Crohn's disease (CD) is often associated with antibodies to microbial
      antigens. Differences in immune response may offer clues to the pathogenesis of
      the disease. The aim was to examine the influence of age at diagnosis on the
      serologic response in children with CD. METHODS: Data were drawn from 3 North
      American multicenter pediatric inflammatory bowel disease (IBD) research
      consortia. At or shortly after diagnosis, pANCA, ASCA IgA, ASCA IgG, anti-ompC,
      and anti-CBir1 were assayed. The results were compared as a function of age at CD
      diagnosis (0-7 years versus 8-15 years). RESULTS: In all, 705 children (79 <8
      years of age at diagnosis, 626 >or=8 years) were studied. Small bowel CD was less
      frequent in the younger group (48.7% versus 72.6%; P < 0.0001), while colonic
      involvement was comparable (91.0% versus 86.5%). ASCA IgA and IgG were seen in
      <20% of those 0-7 years old compared to nearly 40% of those 8-15 years old (P <
      0.001), while anti-CBir1 was more frequent in the younger children (66% versus
      54%, P < 0.05). Anti-CBir1 detected a significant number of children in both age
      groups who otherwise were serologically negative. Both age at diagnosis and site
      of CD involvement were independently associated with expression of ASCA and anti
      CBir1. CONCLUSIONS: Compared to children 8-15 years of age at diagnosis, those 0
      7 years are more likely to express anti-CBir1 but only half as likely to express
      ASCA. These age-associated differences in antimicrobial seropositivity suggest
      that there may be different, and as yet unrecognized, genetic, immunologic,
      and/or microbial factors leading to CD in the youngest children.

PMID- 19107779
TI  - Antinuclear antibodies: a marker associated with steroid dependence in patients
      with ulcerative colitis.
AB  - BACKGROUND: The autoimmune phenomena and the autoantibody profile have acquired
      great importance in ulcerative colitis (UC). Few studies have explored
      antinuclear antibodies (ANAs) prevalence, but not its association with steroid
      dependence. We hypothesized that ANAs could be a factor associated to steroid
      dependence. METHODS: Ninety-seven consecutive patients with UC were included. ANA
      titers and staining patterns were determined by indirect immunofluorescence.
      Gender, age, follow-up time, C-reactive protein (CRP), disease extent, Mayo Score
      Activity Index, extraintestinal manifestations, and steroid dependence were
      analyzed in univariate and multivariate models. RESULTS: Ninety-seven patients
      were included and 49 (50.5%) were females; mean age was 41.7 +/- 22.2 years.
      Positivity for ANAs was encountered in 52 (53.5%) patients, and none for anti
      dsDNA. The prevalence of ANAs was higher in steroid-dependent than in nonsteroid
      dependent patients (77.8% versus 48.1%, P = 0.020; odds ratio [OR] = 3.8, 95%
      confidence interval [CI] 1.1-12.5), and in those with uveitis (100% versus 51.1%;
      P = 0.040) or pyoderma gangrenosum (100% versus 51.6%; P = 0.078). No association
      was observed with gender, age, CRP, disease extent, and Mayo Score Activity
      Index. The multiple regression analysis model showed an association between
      steroid dependence and ANAs (P = 0.033, OR = 3.9, 95% CI 1.4-14.9). CONCLUSIONS:
      ANAs are associated with steroid dependence in UC patients. Further studies are
      required to determine the role of ANAs as serological markers for prediction of
      steroid dependence in order to perform early therapeutic interventions with
      biological agents.

PMID- 19107781
TI  - Associations between ABCB1/MDR1 gene polymorphisms and Crohn's disease: a gene
      wide study in a pediatric population.
AB  - BACKGROUND: Functional studies support the involvement of the MDR1 gene in the
      pathways leading to Crohn's disease (CD). Two common single nucleotide
      polymorphisms (SNPs), C3435T and G2677T/A, thought to alter the function of the
      corresponding P-glycoprotein, have shown inconsistent associations with CD. We
      investigated whether DNA variants in the MDR1 gene were associated with
      susceptibility for CD and specific phenotypes in children. METHODS: A case
      control study was conducted at 3 gastroenterology clinics across Canada. Children
      with CD and population- or hospital-based controls were included. CD cases were
      classified using the Montreal Classification. Thirteen tag-SNPs and the C3435T
      variant in the MDR1 gene were genotyped. Single-SNP allelic, genotype as well as
      gene-wide haplotype associations with CD and its phenotypes at diagnosis were
      assessed. RESULTS: A total of 270 CD cases and 336 controls were studied. Most
      cases were male (56.3%), had disease location L3+/-L4 (58.1%), and an
      inflammatory phenotype B1+/-p (88.5%). Allelic association analysis revealed that
      SNP rs17327442 was significantly associated with overall susceptibility to CD
      (odds ratio [OR] = 0.72, 95% confidence interval [CI] = 0.50-0.99, P = 0.04) but
      this association did not withstand corrections for multiple testing (q-value =
      0.56). Genotype-phenotype analysis indicated that 2 SNPs (rs10248420, P = 0.007,
      q-value = 0.07; rs2032583, P = 0.01, q-value = 0.07) were significantly
      associated with colonic disease. Five SNPs, rs1128503 (P = 0.02), rs1202184 (P =
      0.008), rs1202186 (P = 0.02), rs2091766 (P = 0.03), and rs2235046 (P = 0.03) were
      nominally associated with noninflammatory CD. Specific haplotypes comprising of
      the tag-SNPs were significantly associated with either colonic or noninflammatory
      CD. CONCLUSIONS: Our comprehensive gene-wide analysis suggests that the MDR1 gene
      may be associated with clinical phenotypes of CD in children.

PMID- 19107780
TI  - Components and properties of the G3 ganglion cell circuit in the rabbit retina.
AB  - Each point on the retina is sampled by about 15 types of ganglion cell, each of
      which is an element in a circuit also containing specific types of bipolar cell
      and amacrine cell. Only a few of these circuits are well characterized. We found
      that intracellular injection of Neurobiotin into a specific ganglion cell type
      targeted by fluorescent markers also stained an asymmetrically branching ganglion
      cell. It was also tracer-coupled to an unusual type of amacrine cell whose
      dendrites were strongly asymmetric, coursing in a narrow bundle from the soma in
      the dorsal direction only. The dendritic field of the ganglion cell stratifies
      initially in sublamina b (the ON layers), but with few specializations and
      branches, and then more extensively in sublamina a (the OFF layers) at the level
      of the processes of the coupled amacrine cell. Intersections of the ganglion and
      amacrine cell processes contain puncta immunopositive for Cx36. Additionally, we
      found that the dopaminergic amacrine cell makes contact with both the ganglion
      cell and the amacrine cell, and that a bipolar cell immunopositive for calbindin
      synapses onto the sublamina b processes of the ganglion cell. Dopamine D(1)
      receptor activation reduced tracer flow to the amacrine cells. We have thus
      targeted and characterized two poorly understood retinal cell types and placed
      them with two other cell types in a substantial portion of a new retinal circuit.
      This unique circuit comprised of pronounced asymmetries in the ganglion cell and
      amacrine cell dendritic fields may result in a substantial orientation bias.

PMID- 19107782
TI  - Clinical features and outcome of patients with inflammatory bowel disease who use
      narcotics: a case-control study.
AB  - BACKGROUND: The role of narcotic use in patients with inflammatory bowel disease
      (IBD) is poorly defined. We sought to determine the clinical features of patients
      with IBD who use narcotics and factors associated with the discontinuation of
      narcotics. METHODS: A centralized index was used to identify 100 cases (patients
      with IBD receiving narcotics) and 100 matched controls evaluated in an IBD clinic
      between 1999 and 2002. Associations of clinical factors with case or control
      status were summarized as overall percentages and assessed using conditional
      logistic regression. Associations within cases were assessed using Fisher's exact
      test. RESULTS: Review of 361 charts identified 100 patients with IBD receiving
      narcotics (cases). One hundred matched controls were then identified. Cases were
      significantly associated with: female gender (64% cases versus 45% controls, P =
      0.01), >or=2 IBD-related surgeries (42% versus 17%, P < 0.001), moderate-to
      severe pain (93% versus 20%, P < 0.001), and moderate-to-severe symptoms (83%
      versus 33%, P < 0.001). Significant associations were detected for depression
      (42% versus 19%, P < 0.001), anxiety (19% versus 7%, P = 0.02), history of abuse
      (sexual, emotional, or physical, 17% versus 3%, P = 0.006), and for substance
      abuse (excluding alcohol) (14% versus 1%, P = 0.01). Of 39 cases that returned
      for follow-up, 22 (56%) had discontinued narcotics. Discontinuing narcotics was
      associated with medical treatment adherence (100% versus 53%), none-to-mild pain
      (73% versus 18%), and none-to-mild clinical activity (80% versus 24%).
      CONCLUSIONS: Narcotic use in IBD patients is associated with female gender, >or=2
      previous surgeries, moderate to severe pain, and clinical disease activity,
      depression, anxiety, sexual, emotional and physical abuse, and substance abuse.

PMID- 19107783
TI  - Long-term outcome of maintenance infliximab therapy in children with Crohn's
      disease.
AB  - BACKGROUND: Infliximab therapy has short-term benefits in children with moderate
      to-severe Crohn's disease (CD). We assessed the long-term outcome of infliximab
      maintenance therapy in children with CD. METHODS: We performed a multicenter
      cohort study of 729 pediatric patients with CD enrolled in the Pediatric
      Inflammatory Bowel Disease Collaborative Research Group Registry. Children
      younger than 16 years and newly diagnosed with CD were eligible for this study.
      Disease and medication information were collected prospectively from the treating
      physician at diagnosis, 30 days, and quarterly thereafter. No interventions were
      specified, per protocol. RESULTS: In all, 202 of 729 patients received
      infliximab: 62%, 23%, and 15% within 1, 1-2, and >2 years of diagnosis,
      respectively. The mean age at infliximab initiation was 12.7 years. A total of
      158 infliximab-treated patients received maintenance therapy, 29 episodic (8
      converted to maintenance), and 15 had incomplete follow-up. Among 128 patients
      administered maintenance infliximab and followed for >or=1 year, concomitant
      medications at infliximab initiation included corticosteroids (52%) and
      immunomodulators (90%). By 1, 2, and 3 years, <10% of patients continuing on
      maintenance infliximab were receiving corticosteroids (P < 0.001). Following
      maintenance therapy initiation, 26%, 44%, and 33% of patients continuing on
      maintenance infliximab over 0-1, 1-2, and 2-3 years, respectively, had clinically
      inactive disease not requiring corticosteroids or surgery. The likelihood of
      continuing maintenance infliximab at 1, 2, and 3 years was 93%, 78%, and 67%,
      respectively. CONCLUSIONS: Infliximab maintenance therapy was a durable and
      effective treatment that was associated with prolonged corticosteroid withdrawal
      over a 3-year period in children with CD.

PMID- 19107784
TI  - Association between early-life factors and risk of child-onset Crohn's disease
      among Victorian children born 1983-1998: a birth cohort study.
AB  - BACKGROUND: The incidence of Crohn's disease (CD) with onset before age 16 has
      increased. Several perinatal characteristics have been associated with CD. Our
      objective was to examine the temporal change in CD incidence by period of birth
      and the extent that this could be attributed to perinatal characteristics
      associated with higher CD risk. METHODS: A record linkage study was conducted
      utilizing the perinatal records of Victorian births 1983-1998 inclusive and a
      state-based CD registry. Proportional hazards models were used to investigate the
      perinatal factors in relation to the onset of CD by age 16. Further, a nested
      case control study was conducted to examine the association between sibling
      exposure and CD risk. RESULTS: The CD incidence rate for births 1983-1998 was
      2.01 (95% confidence interval [CI] 1.79, 2.27) per 100,000 child-years. A birth
      cohort effect was demonstrated, with higher CD risk for 1992-1998 versus 1983
      1991 births (hazard ratio [HR] 1.56; 95% CI 1.18, 2.06). Perinatal
      characteristics associated with higher CD risk included urban location, higher
      socioeconomic status, married mother, a congenital abnormality and delivery by
      elective cesarean section. Sibling exposure during the first 6 years of life was
      not associated with CD risk. The increased CD incidence among more recent births
      was not accounted for by changes in these measured perinatal factors.
      CONCLUSIONS: The temporal increase in CD incidence documented for births up to
      1990 has continued for children born after 1991 and was not accounted for by
      temporal changes in the measured perinatal factors.

PMID- 19107785
TI  - Fecal calprotectin complements routine laboratory investigations in diagnosing
      childhood inflammatory bowel disease.
AB  - BACKGROUND: We aimed to study fecal calprotectin in Scottish children with
      inflammatory bowel disease (IBD) and compare its diagnostic accuracy with blood
      parameters. METHODS: Stool samples from 48 Scottish children (29 males, 19
      females) had calprotectin measured at IBD diagnosis. The median age at diagnosis
      was 11.2 years (interquartile range [IQR] 8.7-13.0 years). There were 33 patients
      with Crohn's disease, 5 with ulcerative colitis, and 10 with IBD type
      unspecified. IBD was diagnosed by standard criteria. Calprotectin was measured
      using a commercially available kit (PhiCal Test) and 47/48 patients had
      comparative blood results available at diagnosis. RESULTS: The fecal calprotectin
      concentrations were raised in 96% (46/48) of patients studied. The median
      calprotectin value was 750 microg/g (IQR 235.8-1251 microug/g). In comparison
      with standard blood tests, 32/45 (71.1%) had abnormal erythrocyte sedimentation
      rate, 19/38 (50.0%) had abnormal C-reactive protein, 29/46 (63.0%) had raised
      platelets, 12/45 (26.7%) had hypoalbuminemia, and 38/46 (82.6%) had abnormal
      hemoglobin. We identified 7/47 (14.9%) patients with raised calprotectin at
      diagnosis who did not have any abnormalities detected in the blood tests
      performed. All 48 patients (100%) had at least 1 abnormal blood test and/or
      raised calprotectin at diagnosis. CONCLUSIONS: Calprotectin is significantly more
      likely to be raised than any commonly employed blood tests at IBD diagnosis. When
      used in combination with these bloods tests an abnormality was demonstrated in 1
      or both tests in all patients at diagnosis in this study. Fecal calprotectin
      measurement is a significant advance when used contemporaneously and in addition
      to a routine panel of blood tests in the diagnosis of pediatric IBD.

PMID- 19107786
TI  - In vitro and in vivo degradation of poly(1,3-diamino-2-hydroxypropane-co-polyol
      sebacate) elastomers.
AB  - Biomaterials with a wide range of tunable properties are desirable for
      application-specific purposes. We have previously developed a class of
      elastomeric poly(ester amides) based on the amine alcohol 1,3-diamino-2
      hydroxypropane termed poly(1,3-diamino-2-hydroxypropane-co-polyol sebacate) or
      APS. In this work, we have synthesized and characterized formulations of APS
      polymers and studied the degradation of these polymers in vitro and in vivo. It
      was found that the chemical, physical, and mechanical properties of APS polymers
      could be tuned by adjusting monomer feed ratios and polymerization conditions.
      The degradation kinetics could also be greatly influenced by altering the
      formulation of APS polymers. In vivo degradation half-lives ranged from 6 to
      approximately 100 weeks. Furthermore, the dominant degradation mechanism (i.e.
      hydrolytic or enzymatic) could be controlled by adjusting the specific
      formulation of the APS polymer. On the basis of the observed in vitro and in vivo
      biodegradation phenomena, we also propose that the primary modes of degradation
      are composition dependent.

PMID- 19107787
TI  - Polar surface chemistry of nanofibrous polyurethane scaffold affects annulus
      fibrosus cell attachment and early matrix accumulation.
AB  - Regeneration of the annulus fibrosus (AF), one of the three components of the
      intervertebral disc (IVD), is challenging because of the tissue complexity and
      our limited knowledge about AF cell biology. The purpose of this study was to
      determine if modulating surface chemistry of polycarbonate polyurethane (PU)
      scaffolds would influence annulus fibrosus cell adhesion and early tissue
      formation. To vary surface energy, a novel anionic dihydroxyl oligomer (ADO) was
      synthesized and incorporated into the PU base polymer at three different
      concentrations [0.05, 0.5, and 5% (wt %)]. The polymeric materials were
      fabricated into nanoscale fibrous scaffolds using electrospinning. PU nanofibrous
      scaffolds in the absence or presence of different amounts of ADO were similar in
      appearance. Surface energy was significantly enhanced with increasing ADO
      content, as indicated by the decreasing water contact angle measurements.
      Increasing the material surface's polar character for the scaffolds resulted in a
      positive enhancement of AF cell attachment. The mechanism of this effect was
      complex as at higher ADO concentrations, increased cell adhesion was mediated by
      both serum and newly synthesized proteins, whereas at low ADO concentrations the
      latter had minimal effect. Collagen but not proteoglycan accumulation was also
      modulated by increasing ADO content. This study demonstrated that nanoscale
      fibrous PU scaffolds containing ADO may be appropriate candidates in the
      formation of tissue engineered annulus fibrosus tissue, and that material surface
      polar character can be used to influence AF cell attachment and collagen
      accumulation.

PMID- 19107788
TI  - Degradation behavior of poly(glycerol sebacate).
AB  - Poly(glycerol sebacate) (PGS), a promising scaffold material for soft tissue
      engineering applications, is a soft, tough elastomer with excellent
      biocompatibility. However, the rapid in vivo degradation rate of PGS limits its
      use as a scaffold material. To determine the impact of crosslink density on
      degradation rate, a family of PGS materials was synthesized by incrementally
      increasing the curing time from 42 to 144 h, at 120 degrees C and 10 mTorr
      vacuum. As expected, PGS became a stiffer, tougher, and stronger elastomer with
      increasing curing time. PGS disks were subcutaneously implanted into rats and
      periodically harvested; only mild tissue responses were observed and the
      biocompatibility remained excellent. Regardless of crosslink density, surface
      erosion degradation was observed. The sample dimensions linearly decreased with
      implantation time, and the mass loss rates were constant after 1-week
      implantation. As surface erosion degradation frequently correlates with enzymatic
      digestion, parallel in vitro digestion studies were conducted in lipase solutions
      which hydrolyze ester bonds. Enzymatic digestion played a significant role in
      degrading PGS, and the mass loss rates were not a function of curing time.
      Alternative chemistry approaches will be required to decrease the enzymatic
      hydrolysis rate of the ester bonds in PGS polymers.

PMID- 19107789
TI  - Nanomechanical properties of calcification, fibrous tissue, and hematoma from
      atherosclerotic plaques.
AB  - Clinical events such as heart attack and stroke can be caused by the rupture of
      atherosclerotic plaques in artery walls. Computational modeling is often used to
      better understand atherosclerotic disease progression to identify "vulnerable"
      plaques (i.e., those likely to rupture) and to tailor treatments according to
      tissue composition. However, because of the heterogeneity of plaque tissue, there
      are limited data available on the material properties of individual plaque
      constituents. The goal of this study was to use nanoindentation to measure the
      mechanical properties of blood clots, fibrous tissue, partially calcified fibrous
      tissue, and bulk calcifications from human atherosclerotic plaque tissue. Fourier
      transform infrared (FTIR) spectroscopy was used to quantify the amount of mineral
      and lipid in each tissue region tested. The results demonstrate that the
      stiffness of plaque tissue increases with increasing mineral content. In
      addition, by providing the first experimental data on atherosclerotic
      calcifications, these data show that some of the estimated modulus values
      commonly used in computational models greatly underestimate the stiffness of the
      fully calcified tissue.

PMID- 19107790
TI  - In vivo production of nanosized metal wear debris formed by tribochemical
      reaction as confirmed by high-resolution TEM and XPS analyses.
AB  - High-resolution transmission electron microscopy (TEM) and X-ray photoelectron
      spectroscopy (XPS) were used to establish the link between particles isolated
      from periprosthetic tissue of metal-on-metal (MOM) bearing and the solid deposit
      at the surface of retrieved MOM hip components. The high resolution of TEM made
      it possible to identify individual CoCrMo wear particles. Two shapes were
      observed. Needle-shaped particles ranged from 40 to 120 nm and contained both Co
      and Cr. Globular particles ranged up to 90 nm and contained high levels of Cr and
      no Co. Ti- and Ca-based particles were also identified. XPS analysis of the areas
      of thick solid deposit on the retrieved femoral head showed that the base alloy
      was covered by up to nearly 1-microm thick layer containing carbon, nitrogen, and
      oxygen. This layer was organic in nature, presumably protein-related. In areas
      with a thinner deposit, an organic-related layer was mixed with layers of metal
      oxides, the latter being much thinner than the extensive organic, carbon-rich
      layer. Outside the area of the deposit, the passive oxidized chromium layer was
      thinner, less than 20 nm, and carbon was bound to nonorganic oxygen.

PMID- 19107791
TI  - In vitro biocompatibility of hydroxyapatite-reinforced polymeric composites
      manufactured by selective laser sintering.
AB  - The selective laser sintering (SLS) technique was used to manufacture
      hydroxyapatite-reinforced polyethylene and polyamide composites as potential
      customized maxillofacial implants. In vitro tests were carried out to assess
      cellular responses, in terms of cell attachment, morphology, proliferation,
      differentiation, and mineralized nodule formation, using primary human osteoblast
      cells. This study showed that the SLS composite processed was biocompatible, with
      no adverse effects observed on cell viability and metabolic activity, supporting
      a normal metabolism and growth pattern for osteoblasts. Positive von Kossa
      staining demonstrated the presence of bone-like mineral on the SLS materials.
      Higher hydroxyapatite content composites enhanced cell proliferation, increased
      alkaline phosphatase activity, and produced more osteocalcin. The present
      findings showed that SLS materials have good in vitro biocompatibility and hence
      demonstrated biologically the potential of SLS for medical applications.

PMID- 19107792
TI  - Synthesis and characterization of recombinant factor VIIa-conjugated magnetic
      iron oxide nanoparticles for hemophilia treatment.
AB  - Maghemite (gamma-Fe(2)O(3)) nanoparticles of 15.0 +/- 2.1 nm in diameter were
      prepared by nucleation, followed by controlled growth of magnetic iron oxide thin
      films onto gelatin nuclei. Functionalization of these magnetic nanoparticles with
      activated double bonds was accomplished by interacting divinyl sulfone with the
      gelatin coating of the gamma-Fe(2)O(3) nanoparticles. The activated double bonds
      were then used for covalent binding, via Michael addition reaction, of
      recombinant factor VIIa and human serum albumin to the surface of these
      nanoparticles. Recombinant factor VIIa was also physically bound to the magnetic
      nanoparticles by interacting this factor with the human serum albumin conjugated
      gamma-Fe(2)O(3) nanoparticles. The influence of factor VIIa concentration on the
      immobilization yield has been elucidated. Leakage of the bound factor VIIa into
      PBS containing 4% albumin was insignificant. The coagulant activity of the
      physically adsorbed recombinant factor VIIa was similar to that of the free one
      and was significantly better than that of the covalently bound. The blood half
      life of free factor VIIa is short, about 2-3 h, because of digestion by
      proteolytic enzymes and inhibitory effects. Stabilization of factor VIIa against
      trypsin (a model proteolytic enzyme) and chloromethyl ketone-type inhibitor was
      accomplished by conjugation of the factor to the gamma-Fe(2)O(3) nanoparticles.
      This stabilization may extend the blood half-life of factor VIIa. Therefore, IV
      injection of factor VIIa conjugated gamma-Fe(2)O(3) nanoparticles instead of free
      factor may avoid the frequent dosing and reduce the cost of hemophilia treatment.

PMID- 19107793
TI  - Biological evaluation of a novel chitosan-PVA-based local delivery system for
      treatment of periodontitis.
AB  - In the study, we intend to design a suitable localized drug delivery system
      (LDDS) with chitosan and poly vinyl alcohol (PVA) for treating serve
      periodontitis. For that, a novel formulation based on the incorporation of
      chitosan-based microspheres into PVA film was prepared. As the core parts of the
      novel formulation, chitosan-based microspheres were prepared form chitosan and/or
      carboxymethyl-chitosan (CM-chitosan) by using water-in-oil emulsification method.
      Then basic in vitro and in vivo experiments focusing on biocompatibility and
      biodegradability of the two chitosan-based microspheres were carried out to
      evaluate the feasibility of the novel LDDS. In vitro tests, besides having no
      hemolysis, chitosan microsphere (Cs1-Ms), and CM-chitosan microsphere (Cs2-Ms)
      have adsorbed little proteins on their surfaces. Moreover, plasma proteins
      adsorbed on Cs2-Ms, most of which can easily desorbed, are much less than that
      adsorbed on Cs1-Ms. This indicates that Cs2-Ms perhaps has better
      biocompatibility than Cs1-Ms. In vivo tests, Cs1-Ms and Cs2-Ms were
      subcutaneously implanted in rat to investigate the host tissue inflammatory
      response. Implantations of Cs1-Ms and Cs2-Ms induced a little more severe
      inflammation when compared with the implantation of PVA film. However, the
      difference on in vivo biocompatibility between Cs1-Ms and Cs2-Ms could not be
      confirmed by the implantation model of our experiments. Both Cs1-Ms and Cs2-Ms
      had suffered bioerosion when they were subcutaneously implanted. The hard and
      compact matrixes of Cs1-Ms were degraded very slowly, and only some trifling
      degradation had been found until 4 weeks of implantation. In contrast, Cs2-Ms is
      soft and more hydrophilic, and can be quickly degraded in a form of diffluence by
      the physiological circumstance. All these results suggested that Cs2-Ms had
      better potentials used as core parts of the novel designed LDDS in the future
      developments.

PMID- 19107794
TI  - Injectable cell-free template for bone-tissue formation.
AB  - Here we present a novel injectable hydrogel which forms a template for de novo
      formation of bone tissue. Hydrogel formation takes place in situ in less than 1
      min by the cross-linking of multifunctional hyaluronic acid and polyvinyl alcohol
      derivatives. Endogenous cells are recruited in vivo by incorporating bone
      morphogenetic protein-2 (BMP-2), a powerful promoter for osteogenic
      differentiation. The hydrogel was evaluated in vitro by performing a cell
      viability test and a release study and in vivo by a rat ectopic model.
      Examination by X-ray, microcomputed tomography, and histology revealed a
      significant bone formation at the target site for gels containing BMP-2, and a
      complete degradation was observed for gels without BMP-2 four weeks after
      injection. There were no signs of inflammation or foreign body response in either
      group and we believe that this system has the potential as an off-the-shelf
      injectable to be used where bone tissue is needed.

PMID- 19107795
TI  - Role of flagellin in Crohn's disease: emblematic of the progress and enigmas in
      understanding inflammatory bowel disease.
AB  - Elevated immune responses to the enteric microbiota have long been associated
      with inflammatory bowel disease (IBD), especially Crohn's disease. In recent
      years there has been considerable progress in identifying a number of the
      specific bacterial and host molecules whose interactions mediate these responses.
      However, deciphering the role of these interactions in the pathophysiology of IBD
      remains a difficult challenge, in part due to the very complex nature of the
      epithelial cell / microbial / immune cell interactions that play a central role
      in maintaining the gut's well-being. This article reviews such progress and
      discusses these challenges in the context of focusing on 1 particular protein,
      bacterial flagellin.

PMID- 19107797
TI  - In vivo study effect of particulate Bioglass in the prevention of infection in
      open fracture fixation.
AB  - There are many in vitro experiments showing that particulate bioactive glasses
      have a broad and certain antibacterial effect, but there is no report about this
      antibacterial effect in vivo so far. The aim of this study is to examine the
      efficacy of particulate Bioglass in reducing the rate of infection with
      Staphylococcus aureus after the fixation of open tibial fractures in rabbits. The
      test in vivo was carried out with male rabbits split into two groups infected
      with Staphylococcus aureus at the right tibial fracture sites fixed with plate
      and screw, either with or without bioactive glass respectively. Culture results
      show that six of ten rabbits from the control group had a positive culture for
      the strain of Staphylococcus aureus ATCC25923, compared with six of the nine
      rabbits from the Bioglass group. The median radiographic score is 4.5 points for
      the rabbits from the control group and 4 points for the rabbits from the Bioglass
      group. The median histopathological score was 2.5 points for the rabbits in the
      control group and 3 points for the rabbits in the Bioglass group. In conclusion,
      this study showed no significant difference between the rates of infection of two
      groups. Particulate Bioglass did not reduce the rate of infection with
      Staphylococcus aureus after the fixation of open tibial fractures in rabbits.

PMID- 19107796
TI  - Absence of the transcription factor Nfib delays the formation of the basilar
      pontine and other mossy fiber nuclei.
AB  - Transcription factors of the Nuclear Factor I (Nfi) family are important for the
      development of specific neuronal and glial populations in the nervous system. One
      such population, the neurons of the basilar pontine nuclei, expresses high levels
      of Nfi proteins, and the pontine nuclei are greatly reduced in mice lacking a
      functional Nfib gene. Pontine neurons, along with other precerebellar neurons
      that populate the hindbrain, arise from precursors in the lower rhombic lip and
      migrate anteroventrally to reach their final location. Using
      immunohistochemistry, we find that NFI-B expression is specific for mossy fiber
      populations of the precerebellar system. Analysis of the Nfib(-/-) hindbrain
      indicates that the development of the basilar pontine nuclei is delayed, with
      pontine neurons migrating 1-2 days later than in control animals, and that
      significantly fewer pontine neurons are produced. While the mossy fiber nuclei of
      the caudal medulla do form, they also exhibit a developmental delay. Nfia and
      Nfix null mice exhibit no apparent pontine phenotype, implying specificity in the
      action of NFI family members. Collectively, these data demonstrate that Nfib
      plays an important role in the generation of precerebellar mossy fiber neurons,
      and may do so at least in part by regulating neurogenesis.

PMID- 19107798
TI  - Adhesion of amorphous calcium phosphate composites bonded to dentin: a study in
      failure modality.
AB  - AIMS: As a bioactive filler capable of remineralizing tooth structures, the main
      disadvantage of as-made amorphous calcium phosphate (am-ACP) are its large
      agglomerates. The objective of this study was to mill ACP, and compare the
      adhesive strength with dentin, work to fracture, and failure modes of both groups
      to glass-filled composites and one commercial compomer after 24 h, 1 week, 1, 3,
      and 6 months of exposure to simulated saliva solution (SLS). Flat dentin surfaces
      were acid-etched, primed, and photopolymerized. Composites were applied, photo
      cured, and debonded in shear. The resin used in each composite was identical:
      ethoxylated bisphenol A dimethacrylate, triethylene glycol dimethacrylate, 2
      hydroxyethyl methacrylate, and methacryloxyethyl phthalate. Fillers consisted of
      am-ACP and milled ACP (m-ACP), and a strontium-containing glass (Sr-glass) at
      respective mass fractions of (40, 60, and 75%). FINDINGS: Ninety percent of the
      fracture surfaces in this study showed adhesive failure, with most of these
      occurring at the dentin/primer interface. Fifty-two percent of failures after 24
      h immersion occurred at the primer/composite interface. After 6 months of SLS
      exposure, 80% of specimens failed at the dentin/primer interface, with a 42%
      overall reduction in bond strength. CONCLUSIONS: Milled ACP composites showed
      initial mechanical advantages over am-ACP composites and the compomer, and
      produced a higher incidence of a failure mode consistent with stronger adhesion.
      Evidence is provided which suggests that milled ACP composites may offer enhanced
      potential in clinical bonding applications.

PMID- 19107799
TI  - Accelerated aqueous aging simulation of in vivo oxidation for gamma-sterilized
      UHMWPE.
AB  - In vivo oxidation of gamma air-sterilized ultrahigh-molecular-weight polyethylene
      (UHMWPE) has been observed when joint replacement hip and knee components are
      explanted during revision surgery. The purpose of the present study was to extend
      a previously published accelerated aging protocol for gamma-sterilized UHMWPE.
      Unsterilized and gamma-sterilized GUR 1150 resin samples were aged in phosphate
      buffered saline (PBS) at 40 or 50 degrees C for up to 52 weeks. Under these
      conditions, slower changes in oxidation index (OI) occurred than those previously
      observed by aging at 60 degrees C. Reduction of aging temperature below 60
      degrees C also changed the kinetics of oxidation such that the aldehyde peak
      (1732 cm(-1)) present at higher temperature was eliminated making the
      ketone/carboxylic acid region (1713-1718 cm(-1)) the primary region contributing
      to the calculation of the OIs for each group. The oxidation profiles obtained
      after 52 weeks at 40 and 50 degrees C were consistent with retrievals that have
      undergone low oxidation, associated with maximum OI values of less than 1. Aging
      at 50 degrees C represents a compromise between the slower oxidation rate of in
      vivo temperatures and the nonphysiological kinetics of elevated temperatures in
      an aqueous environment. However, even at 50 degrees C over a year of in vitro
      aqueous aging will be necessary to reproduce the oxidation levels observed in
      long-term implanted acetabular retrievals. (

PMID- 19107800
TI  - Polymeric particle formation through electrospraying at low atmospheric pressure.
AB  - Electrospraying is a simple and versatile technique capable of producing
      polymeric particles. However, most investigations carried out thus far have been
      performed at ambient atmospheric pressure without studying the influences of
      pressure on the formation of polymeric particles. Here, we report our
      investigation on the effects of varying the pressure and the solution
      concentration on the microstructures of electrosprayed polymeric particles.
      Pressures are varied from ambient atmospheric pressure to 380 mmHg below ambient
      pressure, and solution concentrations are varied over a range of 3-7 w/v %. By
      varying these parameters, we manipulated the rate of solvent evaporation and the
      solidification of the electrosprayed particles. The results show that changes to
      the pressure had significant effects on the microstructure and morphology of
      poly(epsilon-caprolactone) (PCL) particles. The average particle size became
      larger as the chamber pressure decreased. At a solution concentration of 5 w/v %
      and a pressure 150 mmHg below ambient pressure, uniform and spherical PCL
      particles were generated. Electrospun fibers were formed when a solution
      concentration of 7 w/v % was used. The developed technique can be applied to
      prepare polymeric drug delivery carriers though a low-pressure-assisted spray
      drying method, and is particularly suitable for fabricating delivery microspheres
      encapsulated with temperature-sensitive drugs and biomolecules.

PMID- 19107801
TI  - Biomechanical and histomorphometric evaluation of a thin ion beam bioceramic
      deposition on plateau root form implants: an experimental study in dogs.
AB  - The aim of this study was to evaluate the biomechanical fixation, bone-to-implant
      contact, and bone morphology of an ion beam assisted deposition of a 300-500 nm
      thick Ca- and P-based bioceramic surface on a previously alumina-blasted/acid
      etched Ti-6Al-4V implant surface in a dog model. MATERIALS AND METHODS: Thirty
      six 4.5 x 11 mm plateau root form implants, control (alumina-blasted/acid-etched
      AB/AE) and test groups (AB/AE+300-500 nm bioceramic coating, Nanotite) were
      placed along a proximal tibia of six beagle dogs remaining for 2 and 4 weeks (n =
      3 animals per implantation time). Following euthanization, the implants were
      torqued to interface fracture at approximately 0.196 radians/sec until a 10%
      maximum load drop was detected. The implants in bone were nondecalcified
      processed to approximately 30 microm thickness slides for histomorphologic and
      bone-to-implant contact (BIC) assessment. Statistical analyses for torque to
      interface fracture were performed using a mixed model ANOVA, and BIC was
      evaluated by the chi2 test at 95% level of significance. RESULTS: At 4 weeks,
      significantly higher torque to interface fracture was observed for the Test
      implant surface. Histomorphologic analysis showed higher degrees of bone
      organization for test implants compared to control at 2 and 4 weeks.
      Significantly higher BIC was observed at 4 weeks compared to 2 weeks (no
      statistical differences between control and test implants). CONCLUSION: The
      higher torque to interface fracture and increased bone maturity obtained in this
      study support that the surface modification comprising a 300-500 nm Ca- and P
      based bioceramic coating positively influenced healing around pleateau root form
      implants.

PMID- 19107802
TI  - Rietveld structure and in vitro analysis on the influence of magnesium in
      biphasic (hydroxyapatite and beta-tricalcium phosphate) mixtures.
AB  - The structure of two different Mg-substituted biphasic (HAP and beta-TCP)
      mixtures along with the biphasic mixtures without substituted Mg(2+) was
      investigated using Rietveld refinement technique. The substituted Mg(2+) was
      found in the beta-TCP phase and its influence on the composition has led to an
      increase in HAP content of Mg-containing biphasic mixtures when compared with the
      HAP content detected in pure biphasic mixtures. The refined structural parameters
      of Ca(10)(PO(4))(6)(OH)(2) and beta-Ca(3)(PO(4))(2) confirmed that all the
      investigated compositions have crystallized in the corresponding hexagonal (space
      group P6(3)/m) and rhombohedral (space group R3c) structures. The substitution of
      lower sized magnesium was found preferentially incorporated at the sixfold
      coordinated Ca (5) site of beta-TCP, which is due to the strong Ca (5).O
      interaction among all the five different Ca sites of beta-Ca(3)(PO(4))(2). The in
      vitro tests using primary culture of osteoblasts showed that all the tested
      samples are biocompatible and promising materials for in vivo studies.

PMID- 19107803
TI  - Faster and stronger vascular "Biotube" graft fabrication in vivo using a novel
      nicotine-containing mold.
AB  - To accelerate the fabrication of in vivo-tissue engineered autologous vascular
      prosthetic tissues, the "Biotube," a novel drug-coating mold was designed. The
      mold was prepared by impregnating nicotine as a model drug into a gelatinous
      matrix coated on acrylate rods (diameter, 2 mm; length, 20 mm). Upon embedding
      the molds into dorsal subcutaneous pouches of rats, completely encapsulated
      Biotubes with significant tissue migration accompanied by rich angiogenesis and
      having 3.8 times as many neovessels as the uncoated controls, were formed at only
      2 weeks. The wall thickness and burst strength of the Biotubes were 399.9 +/-
      135.2 microm and 2682.6 +/- 722.6 mmHg, respectively. These values were,
      respectively, more than 9.6 and 3.2 times greater than the corresponding
      controls. Therefore, it is confidently expected that the mechanical properties of
      Biotubes obtained by nicotine coating make them suitable for application as
      vascular grafts.

PMID- 19107805
TI  - Comparison of the osteoblast and myoblast behavior on hydroxyapatite
      microgrooves.
AB  - Surface topography is one of the most important surface properties of
      biomaterials and microfabrication techniques provide new routes to produce
      precisely controlled surface topographies for investigating the topographic
      effects on cell behavior. In this study, hydroxyapatite (HA) microgrooved
      surfaces were used to study the osteoblast and myoblast response to the surface
      micro-features. The microgrooves were first produced on silicon wafers by
      photolithography, and then coated with HA using sputtering technique. Orientation
      angle (OA) was used to evaluate the contact guidance introduced by microgrooves
      and form index (FI) was introduced to describe the cell morphology change. The
      results show that the microgroove effects on myoblasts are more obvious than
      those on osteoblasts, and the two types of cells are sensitive to different sizes
      of microgrooves. The microgrooves with 8 microm width strongly affect both
      osteoblasts and myoblasts, while the microgrooves with 24 microm width strongly
      affect myoblasts only. These results confirm that the surface topographic effect
      is of cell specific, and therefore, design of surface topographic features must
      be different for myoblasts and osteoblasts.

PMID- 19107804
TI  - Thermomechanical properties, collapse pressure, and expansion of shape memory
      polymer neurovascular stent prototypes.
AB  - Shape memory polymer stent prototypes were fabricated from thermoplastic
      polyurethane. Commercial stents are generally made of stainless steel or other
      alloys. These alloys are too stiff and prevent most stent designs from being able
      to navigate small and tortuous vessels to reach intracranial lesions. A solid
      tubular model and a high flexibility laser etched model are presented. The stents
      were tested for collapse in a pressure chamber. At 37 degrees C, the full
      collapse pressure was comparable to that of commercially available stents, and
      higher than the estimated maximum pressure exerted by intracranial arteries.
      However, there is a potential for onset of collapse, which needs further study.
      The stents were crimped and expanded, the laser-etched stent showed full recovery
      with an expansion ratio of 2.7 and a 1% axial shortening.

PMID- 19107806
TI  - Development of the mouse amygdala as revealed by enhanced green fluorescent
      protein gene transfer by means of in utero electroporation.
AB  - The amygdala is located in the caudal part of the ventral telencephalon. It is
      composed of many subdivisions and is involved in the control of emotion. It is
      important to know the mechanisms of amygdalar development in order to analyze the
      pathogenesis of emotional disorders, but they are still not adequately
      understood. In the present study the migration, differentiation, and distribution
      of amygdalar neurons in the mouse embryo were investigated by means of in utero
      electroporation. Ventricular zone cells in restricted regions, that is, the
      caudal ganglionic eminence (CGE), the ventral pallium, the lateral pallium, and
      the diencephalon, were labeled with an expression vector of the enhanced green
      fluorescent protein (EGFP) gene. Labeling at embryonic day (E)10 revealed that
      the central nucleus originates from the neuroepithelium in the ganglionic
      eminence and the labeling at E11 and E12 revealed that the basolateral complex
      originates from the neuroepithelium of the ventral and lateral pallia. The
      introduction of the EGFP gene into the neuroepithelium of the third ventricle at
      E11 showed that the medial nucleus originates, at least in part, from the
      neuroepithelium of the diencephalon and migrates over the diencephalo
      telencephalic boundary. The radial glial arrangement corresponded well with the
      initial migration of amygdalar neurons, and the radial processes later formed the
      boundary demarcating the basolateral complex. These findings indicate that the
      neurons originating from the temporally and spatially restricted neuroepithelium
      in both the telencephalon and diencephalon migrate and differentiate to form the
      mosaic of amygdalar subdivisions.

PMID- 19107807
TI  - Bisphosphonate determination using 1H-NMR spectroscopy for biomedical
      applications.
AB  - Bisphosphonate is known to be a very active drug in the treatment of osteoporosis
      and bone regeneration. A new method has been developed, utilizing nuclear
      magnetic resonance spectroscopy to identify and measure the amount of
      bisphosphonate in solution. A standard reference with similar functional group to
      that of the bisphosphonate was chosen and applied in the experimentation. The
      results showed that the use of nuclear magnetic resonance spectroscopy ((1)H-NMR)
      in determining the solvent residues of various pharmaceutical drugs has proved to
      be effective. Unlike chromatography, it is possible to use a universal reference
      standard as an internal standard assayed by quantitative NMR. Using the same
      theory, this method is capable of both identifying and quantifying the
      bisphosphonate in various solutions. This paper is the first publication showing
      this unique measurement method, which can be used in a range of pharmaceutical
      and biomedical applications.

PMID- 19107808
TI  - Three-dimensional reconstruction and neural map of the serotonergic brain of
      Asplanchna brightwellii (Rotifera, Monogononta).
AB  - The basic organization of the rotifer brain has been known for nearly a century;
      yet, fine details on its structure and organization remain limited despite the
      importance of rotifers in studies of evolution and population biology. To gain
      insight into the structure of the rotifer brain, and provide a foundation for
      future neurophysiologic and neurophylogenetic research, the brain of Asplanchna
      brightwellii was studied with immunohistochemistry, confocal laser scanning
      microscopy, and computer modeling. A three-dimensional map of serotonergic
      connections reveals a complex network of approximately 28 mostly unipolar,
      cerebral perikarya and associated neurites. Cells and their projections display
      symmetry in quantity, size, connections, and pathways between cerebral
      hemispheres within and among individuals. Most immunopositive cells are
      distributed close to the brain midline. Three pairs of neurites form decussations
      at the brain midline and may innervate sensory receptors in the corona. A single
      neuronal pathway appears to connect both the lateral horns and dorsolateral
      apical receptors, suggesting that convergence of synaptic connections may be
      common in the afferent sensory systems of rotifers. Results show that the neural
      map of A. brightwellii is much more intricate than that of other monogonont
      rotifers; nevertheless, the consistency in neural circuits provides opportunities
      to identify homologous neurons, distinguish functional regions based on
      neurotransmitter phenotype, and explore new avenues of neurophylogeny in
      Rotifera.

PMID- 19107809
TI  - Anatomy and ultrastructure of the female reproductive system of Pleioplana
      atomata (Platyhelminthes: Polycladida).
AB  - The ultrastructure of the female reproductive system of the polyclad flatworm
      Pleioplana atomata is described. Numerous ovaries are scattered throughout the
      entire body but are mainly concentrated on the dorsal side. Within an ovary, a
      germinative zone with oogonia and prefolicular cells is located in the dorsal
      part of the ovary. The remaining part of the gonad is filled with previtellogenic
      and early vitellogenic oocytes enwrapped by follicular cells. During
      previtellogenesis, oocytes produce numerous eggshell globules, which are
      distributed into the cortical area of the cell in later stages. Eventually, these
      globules release their contents into the space between the eggshell cover and
      oolemma. Similar types of globules are also found in others flatworms, and may
      represent useful phylogenetic characters. Entolecital, vitellogenic oocytes pass
      to paired uteri, where vitellogenesis is completed. The remainder of the female
      reproductive system consists of paired thin uterine ducts that join a vagina. The
      distal part of the long, curved vagina forms a large Lang's vesicle, while the
      proximal part is connected to a female atrium leading to a female gonopore. We
      hypothesize that Lang's vesicle functions in the digestion of excess sperm
      received. Two kinds of different shell (cement) glands that release their
      secretion into the vagina are identified. Both are unicellular glands and each
      gland cell connects to the lumen of the vagina via an individual canal. Similar
      glands in other acotylean polyclads have been implicated in the formation of
      eggshell covers.

PMID- 19107810
TI  - Three-dimensional reconstruction of the odontophoral cartilages of
      Caenogastropoda (Mollusca: Gastropoda) using micro-CT: Morphology and
      phylogenetic significance.
AB  - Odontophoral cartilages are located in the molluscan buccal mass and support the
      movement of the radula during feeding. The structural diversity of odontophoral
      cartilages is currently known only from limited taxa, but this information is
      important for interpreting phylogeny and for understanding the biomechanical
      operation of the buccal mass. Caenogastropods exhibit a wide variety of feeding
      strategies, but there is little comparative information on cartilage morphology
      within this group. The morphology of caenogastropod odontophoral cartilages is
      currently known only from dissection and histology, although preliminary results
      suggest that they may be structurally diverse. A comparative morphological survey
      of 18 caenogastropods and three noncaenogastropods has been conducted, sampling
      most major caenogastropod superfamilies. Three-dimensional models of the
      odontophoral cartilages were generated using X-ray microscopy (micro-CT) and
      reconstruction by image segmentation. Considerable morphological diversity of the
      odontophoral cartilages was found within Caenogastropoda, including the presence
      of thin cartilaginous appendages, asymmetrically overlapping cartilages, and
      reflexed cartilage margins. Many basal caenogastropod taxa possess previously
      unidentified cartilaginous support structures below the radula (subradular
      cartilages), which may be homologous to the dorsal cartilages of other
      gastropods. As subradular cartilages were absent in carnivorous caenogastropods,
      adaptation to trophic specialization is likely. However, incongruence with
      specific feeding strategies or body size suggests that the morphology of
      odontophoral cartilages is constrained by phylogeny, representing a new source of
      morphological characters to improve the phylogenetic resolution of this group.

PMID- 19107811
TI  - Ultrastructural investigation of the vesicular glands in Scutigera coleoptrata
      (Chilopoda, Notostigmophora).
AB  - In the notostigmophoran centipedes, two pairs of vesicular glands have evolved.
      These paired glands are situated in the first and second trunk segment and open
      via cuticular ducts in the upper part of the particular pleura. The vesicular
      glands of Scutigera coleoptrata were investigated using light and, for the first
      time, electron microscopical methods. The glands consist of wide sac-like
      cavities that often appear vesicular. The epithelia of both glands are
      identically structured and consist of numerous glandular units. Each of these
      units consists of four different cells: a single secretory cell, a small
      intermediary cell, and one proximal and one distal canal cell. The intermediary
      cell forms a conducting canal and connects the secretory cell with the canal
      cells. Proximally, the intermediary cell bears microvilli, whereas the distal
      part is covered with a distinct cuticle. The cuticle is a continuation of the
      cuticle of the canal cells. This investigation shows that the ultrastructure of
      glandular units of the vesicular glands is comparable to that of the glandular
      units of other epidermal glands in Chilopoda and Diplopoda, although the glands
      look completely different in the light microscope. Thus, it is likely that the
      vesicular glands and epidermal glands share the same ground pattern. With regard
      to specific differences in the cuticular lining of the intermediary cells, a
      common origin of epidermal glands in Myriapoda and Hexapoda is not supported.

PMID- 19107812
TI  - Morphological and histological organization of the pyriform appendage of the
      tetrabranchiate Nautilus pompilius (Cephalopoda, Mollusca).
AB  - The pyriform appendage, an organ only found in nautiloid cephalopods was
      investigated with histological, histochemical and ultrastructural methods in
      order to characterize the anatomical and the cytological structure of this organ.
      The pyriform appendage is situated within the genital septum and lies in close
      contact with the ventricle of the heart. The proximal side ends blindly near the
      gonad whereas the distal side is developed into a duct. The duct was observed to
      open into the mantle cavity in juvenile and adult Nautilus pompilius of both
      sexes. Injections of India ink in the heart demonstrate that the organ is
      supplied with hemolymph from an artery that extends from the heart. The pyriform
      appendage is a hollow organ consisting mainly of glandular tissue. The lumen is
      covered with a columnar epithelium, the tunica mucosa, consisting of only one
      cell type containing vacuoles with different inclusions. Underneath the tunica
      mucosa is the tunica muscularis, which is embedded in connective tissue and
      folded, enlarging the internal surface. A cuboidal tunica serosa surrounds this
      organ. The vacuoles and the secretory products contain neutral
      mucopolysaccharides, glycoproteins and glycolipids. Acid phosphatase and
      serotonin were localized in the tunica mucosa. Acetylcholinesterase,
      catecholamines and the tetrapeptide FMRF-amide were demonstrated within the nerve
      endings of the tunica muscularis indicating a dual "cholinergic-aminergic"
      neuroregulation, possibly modulated by FMRF-amide. These findings suggest that
      the pyriform appendage is not a rudimentary organ but instead has distinct
      biological functions in nautiloid cephalopods, possibly in intraspecific
      communication.

PMID- 19107813
TI  - Placental ontogeny in Tasmanian snow skinks (genus Niveoscincus) (Lacertilia:
      Scincidae).
AB  - Lizards of the viviparous genus Niveoscincus contributed importantly to a classic
      model for the evolution of placentation of squamate reptiles. This model predicts
      that: (1) placental function is correlated with placental structural complexity
      and (2) the type of chorioallantoic placenta attributed to three species of
      Niveoscincus (N. metallicus, N. ocellatus, N. pretiosus) is intermediate in
      complexity to a highly placentotrophic type of placenta. Recent studies of two of
      these species (N. metallicus, N. ocellatus) revealed additional variation in
      placental structure, as well as variation in the level of placentotrophy; N.
      metallicus is predominantly lecithotrophic, while N. ocellatus is highly
      placentotrophic. We used light microscopy to study placental ontogeny in two
      biennially reproducing species of Niveoscincus (N. greeni, N. microlepidotus) and
      placental morphology in late stage embryos of N. pretiosus. These data, in
      combination with prior studies, provide descriptions of placental structure for
      six of the eight species assigned to this lineage. The genus Niveoscincus has
      greater variation in placental structure than any other squamate lineage. We
      recognize four distinct groupings among these six species based on placental
      structure. The most highly placentotrophic species, N. ocellatus, has a complex
      placental morphology, yet shares these structures with a predominantly
      lecithotrophic species, N. microlepidotus. Thus, among species of Niveoscincus,
      placental structural complexity is not an infallible predictor of overall
      placental function.

PMID- 19107814
TI  - The chiton stylus canal: An element delivery pathway for tooth cusp
      biomineralization.
AB  - A detailed investigation of the stylus canal situated within the iron mineralized
      major lateral teeth of the chiton Acanthopleura hirtosa was undertaken in
      conjunction with a row-by-row examination of cusp mineralization. The canal is
      shown to contain columnar epithelial tissue similar to that surrounding the
      mineralized cusps, including the presence of iron rich particles characteristic
      of the iron storage protein ferritin. Within the tooth core, a previously
      undescribed internal pathway or plume is evident above the stylus canal, between
      the junction zone and mineralizing posterior face of the cusp. Plume formation
      coincides with the appearance of iron in the superior epithelium and the onset of
      mineralization at tooth row 13. The plume persists during the delivery of
      phosphorous and calcium into the tooth core, and is the final region of the cusp
      to become mineralized. The presence of the stylus canal was confirmed in a
      further 18 chiton species, revealing that the canal is common to polyplacophoran
      molluscs. These new data strongly support the growing body of evidence
      highlighting the importance of the junction zone for tooth mineralization in
      chiton teeth, and indicate that the chemical and structural environment within
      the tooth cusp is under far greater biological control than previously
      considered.

PMID- 19107815
TI  - Stereological estimation of the surface area and oxygen diffusing capacity of the
      respiratory stomach of the air-breathing armored catfish Pterygoplichthys
      anisitsi (Teleostei: Loricariidae).
AB  - The stomach of Pterygoplichthys anisitsi has a thin, translucent wall and a
      simple squamous epithelium with an underlying dense capillary network. In the
      cardiac and pyloric regions, most cells have short microvilli distributed
      throughout the cell surface and their edges are characterized by short, densely
      packed microvilli. The mucosal layer of the stomach has two types of pavement
      epithelial cells that are similar to those in the aerial respiratory organs. Type
      1 pavement epithelial cells, resembling the Type I pneumocyte in mammal lungs,
      are flat, with a large nucleus, and extend a thin sheet of cytoplasm on the
      underlying capillary. Type 2 cells, resembling the Type II pneumocyte, possess
      numerous mitochondria, a well-developed Golgi complex, rough endoplasmic
      reticulum, and numerous lamellar bodies in different stages of maturation. The
      gastric glands, distributed throughout the mucosal layer, also have several cells
      with many lamellar bodies. The total volume (air + tissue), tissue, and air
      capacity of the stomach when inflated, increase along with body mass. The surface
      to-tissue-volume ratio of stomach varies from 108 cm(-1) in the smallest fish
      (0.084 kg) to 59 cm(-1) in the largest fish (0.60 kg). The total stomach surface
      area shows a low correlation to body mass. Nevertheless, the body-mass-specific
      surface area varied from 281.40 cm(2) kg(-1) in the smallest fish to 68.08 cm(2)
      kg(-1) in the largest fish, indicating a negative correlation to body mass (b = 
      0.76). The arithmetic mean barrier thickness between air and blood was 1.52 +/-
      0.07 microm, whereas the harmonic mean thickness (tau(h)) of the diffusion
      barrier ranged from 0.40 to 0.74 microm. The anatomical diffusion factor (ADF =
      cm(2) microm(-1) kg(-1)) and the morphological O(2) diffusion capacity
      (D(morphol)O(2) = cm(3) min(-1) mmHg(-1) kg(-1)) are higher in the smallest
      specimen and lower in the largest one. In conclusion, the structure and
      morphometric data of P. anisitsi stomach indicate that this organ is adapted for
      oxygen uptake from air.

PMID- 19107816
TI  - Butanol fraction containing berberine or related compound from nexrutine inhibits
      NFkappaB signaling and induces apoptosis in prostate cancer cells.
AB  - BACKGROUND: Epidemiological and laboratory studies support the hypothesis that
      several plant components influence prostate carcinogenesis and holds promise for
      disease prevention. Previously we reported that Nexrutine (bark extract from
      Phellodendron amurense) inhibits proliferation of prostate cancer cells and
      prostate tumor development in the transgenic adenocarcinoma of mouse prostate
      (TRAMP) model through modulation of Akt signaling pathway. In the present
      investigation we conducted studies to further define the mechanism of action of
      Nexrutine and to identify the active component associated with its biological
      activity. METHODS: Androgen-responsive, androgen-independent human prostate
      cancer cell lines and tissues from TRAMP mice fed Nexrutine(R) were used in these
      studies. Activity guided fractionation identified butanol fraction recapitulating
      the activities of Nexrutine assessed by proliferation assays, apoptotic assays
      (DAPI and TUNEL staining), transient transfections, gel shift assays and Western
      blotting. In addition ultra-performance liquid chromatography (UPLC) of butanol
      fraction was used to identify active component of Nexrutine. RESULTS: Butanol
      fraction recapitulated the activities of Nexrutine in (i) inhibiting
      proliferation; (ii) inducing apoptosis; and (iii) modulating transcriptional
      activity of NFkappaB in prostate cancer cells. Our data also indicates that both
      Nexrutine and butanol fraction modulates NFkappaB transcriptional activity by
      inhibiting IkappaBalpha phosphorylation. Expression of p65 and phosphorylated
      IkappaBalpha are high in tumors from TRAMP mice. In contrast dietary
      administration of Nexrutine reduced expression of p65 and phosphorylated
      IkappaBalpha in prostate from TRAMP mice. In addition using UPLC, we have
      identified berberine or closely related compound in the butanol fraction.
      CONCLUSION: The results suggest that berberine or closely related component of
      butanol fraction may be responsible for the observed biological activities and
      induce apoptosis in prostate cancer cells by targeting critical cell survival
      signaling pathways both in vitro and in vivo.

PMID- 19107819
TI  - The pheromonal gland of Lymantria dispar: morphology and evidence for its
      innervation.
AB  - The morphological features of the glandular epithelium that secretes pheromone in
      the polyphagous pest gypsy moth Lymantria dispar are described by light and
      electron microscopy. The monolayered gland cells are covered by the folded
      cuticle of the intersegmental membrane between the 8th and 9th abdominal segments
      showing neither sites of discontinuity nor distinct openings on its external
      surface. The cells bear a large, often irregularly shaped nucleus, and contain
      granules of variable amount and electron-density. These granules are mostly
      located in the basal compartment of the cytoplasm, in a labyrinthine zone laying
      on a basement membrane. The apical membrane of the gland cells bear microvilli
      and cell-cell contact is established by different junctional structures. Nerve
      fibers enwrapped in glia are found beneath the basement membrane, in close
      contact with the secretory cells. This latter finding represents the first
      evidence of the innervation of the pheromonal gland in L. dispar.

PMID- 19107818
TI  - Comparison of navigation accuracy in THA between the mini-anterior and -posterior
      approaches.
AB  - BACKGROUND: The accuracy of a CT-based hip navigation might depend on surgical
      approaches, resulting in varying accuracy of implant alignment. METHODS: We
      performed primary cementless total hip arthroplasty (THA) with mini-incision
      surgery (MIS) to 40 well-matched patients (anterior or posterior approaches, 20
      hips each), using navigation with surface registration. We investigated cup
      alignment using postoperative computed tomography (CT) and compared the
      navigation accuracy between the two approaches, i.e. the difference between intra
      operative and postoperative alignments of the cup. RESULTS: There was no
      significant difference between the two approaches. The mean navigation accuracies
      in abduction and anteversion were 2.0 degrees (SD 1.4 degrees) and 2.7 degrees
      (SD 1.9 degrees), respectively, in the anterior approach, and 2.4 degrees (SD 2.0
      degrees) and 2.0 degrees (SD 1.4 degrees), respectively, in the posterior
      approach. All cup alignments were within 10 degrees of the target orientation.
      CONCLUSIONS: This CT-based navigation for MIS-THA provides navigation accuracy
      without significant differences between the two approaches and with favourable
      alignment of the cup.

PMID- 19107820
TI  - Ultrastructure of the body cavities in Phylactolaemata (Bryozoa).
AB  - Only species belonging to the bryozoan subtaxon Phylactolaemata possess an
      epistome. To test whether there is a specific coelomic cavity inside the
      epistome, Fredericella sultana, Plumatella emarginata, and Lophopus crystallinus
      were studied on the ultrastructural level. In F. sultana and P. emarginata, the
      epistome contains a coelomic cavity. The cavity is confluent with the trunk
      coelom and lined by peritoneal and myoepithelial cells. The lophophore coelom
      extends into the tentacles and is connected to the trunk coelom by two weakly
      ciliated coelomic ducts on either side of the rectum. The lophophore coelom
      passes the epistome coelom on its anterior side. This region has traditionally
      been called the forked canal and hypothesized to represent the site of excretion.
      L. crystallinus lacks an epistome. It has a simple ciliated field where an
      epistome is situated in the other species. Underneath this field, the forked
      canal is situated. Compared with the other species, it is pronounced and exhibits
      a dense ciliation. Despite the occurrence of podocytes, which are prerequisites
      for a selected fluid transfer, there is no indication for an excretory function
      of the forked canal, especially as no excretory porus was found.

PMID- 19107821
TI  - Feeding kinematics and performance of Hawaiian stream gobies, Awaous guamensis
      and Lentipes concolor: linkage of functional morphology and ecology.
AB  - Distributions of Hawaiian stream fishes are typically interrupted by waterfalls
      that divide streams into multiple segments. Larvae hatch upstream, are flushed
      into the ocean, and must climb these waterfalls to reach adult habitats when
      returning back to freshwater as part of an amphidromous life cycle. Stream
      surveys and studies of climbing performance show that Lentipes concolor Gill can
      reach fast-flowing upper stream segments but that Awaous guamensis Valenciennes
      reaches only slower, lower stream segments. Gut content analyses for these two
      species indicate considerable overlap in diet, suggesting that feeding kinematics
      and performance of these two species might be comparable. Alternatively, feeding
      kinematics and performance of these species might be expected to differ in
      relation to the different flow regimes in their habitat (feeding in faster stream
      currents for L. concolor versus in slower currents for A. guamensis). To test
      these alternative hypotheses, we compared food capturing kinematics and
      performance during suction feeding behaviors of A. guamensis and L. concolor
      using morphological data and high-speed video. Lentipes concolor showed both a
      significantly larger gape angle and faster jaw opening than A. guamensis.
      Geometric models calculated that despite the inverse relationship of gape size
      and suction pressure generation, the fast jaw motions of L. concolor allow it to
      achieve higher pressure differentials than A. guamensis. Such elevated suction
      pressure would enhance the ability of L. concolor to successfully capture food in
      the fast stream reaches it typically inhabits. Differences in jaw morphology may
      contribute to these differences in performance, as the lever ratio for jaw
      opening is about 10% lower in L. concolor compared with A. guamensis, suiting the
      jaws of L. concolor better for fast opening.

PMID- 19107822
TI  - Ultrastructure and the importance of wear in the dentition of the halfbeak
      (Pisces: Hemiramphidae) pharyngeal mill.
AB  - To assess how tooth microstructure and composition might facilitate the
      pharyngeal mill mechanism of halfbeaks, apatite structure and iron content were
      determined by scanning electron microscopy and energy dispersive X-ray analysis
      for Hyporhamphus regularis ardelio, Arrhamphus sclerolepis krefftii, and
      Hemiramphus robustus. Iron was present in developing teeth and was concentrated
      along the shearing edge of spatulate incisiform teeth, which dominate the
      occlusive wear zone in all three species. A model based on tooth structure and
      wear rate is proposed to explain how halfbeaks maintain a fully functional
      occlusion zone throughout growth and consequent tooth addition and replacement.
      Replacement teeth erupt and wear rapidly so that a constant occlusion plane is
      always present. Iron within the tooth tissue reduces the wear rate of the cutting
      edge while simultaneously maintaining its sharpness and efficiency.

PMID- 19107823
TI  - Antioxidant and antiinflammatory activity of pine pollen extract in vitro.
AB  - To determine the medicinal properties of pine pollen, the antioxidant and
      antiinflammatory activities of the ethanol extract of pine pollen extract (PPE)
      were investigated. PPE displayed a strong free radical scavenger activity on 1,1
      diphenyl-2-picrylhydrazyl radical and hydrogen peroxide. It was observed also
      that the antioxidant activity, measured by the ferric thiocyanate method,
      increased with the addition of PPE to the linoleic acid emulsion system. PPE was
      also found to inhibit significantly the amount of malondialdehyde and protein
      carbonyls formed from liver homogenate. Like the antioxidant activity, the
      reducing power of PPE was excellent. Thereafter, the study investigated the
      effects of PPE in modulating the production of pro-inflammatory mediators in
      lipopolysaccharide (LPS)-activated RAW 264.7 macrophages, and the effect of PPE
      on interleukin (IL)-1beta-induced matrix metalloproteinases (MMPs) production and
      mitogen-activated protein kinases (MAPKs) activation in the human synovial
      sarcoma cell line, SW982. PPE was found to inhibit the production of nitric
      oxide, tumor necrosis factor-alpha, IL-1 and IL-6 in LPS-activated macrophages.
      Treatment with PPE at 10 microg/mL significantly (p < 0.05) inhibited IL-1beta
      induced MMPs (MMP-1 and -3) production in SW982 cells. IL-1beta-induced JNK
      activation was inhibited by PPE (10 microg/mL), whereas p38 and ERK1/2 were not
      affected. These findings suggest that pine pollen is a potential antioxidant and
      beneficial for inflammatory conditions through down-regulation of JNK and MMPs.

PMID- 19107824
TI  - Search for antimycobacterial constituents from a Tibetan medicinal plant,
      Gentianopsis paludosa.
AB  - From the whole plant of Gentianopsis paludosa seven compounds were isolated and
      identified to be 1,7-dihydroxy-3,8-dimethoxyxanthone (1), 1,7,8-trihydroxy-3
      methoxyxanthone (2), 1-hydroxy-3,7,8-trimethoxyxanthone (3), 1,8-dihydroxy-2,6
      dimethoxyxanthone (4), oleanolic acid (5), 4',5,7-trihydroxyflavone (6) and
      luteolin-7-O-glucoside (7). Compounds 1, 2, 3 and 5 showed modest inhibitory
      effect against the growth of Mycobacterium smegmatis and M. tuberculosis.

PMID- 19107825
TI  - The inhibitory effect on aldose reductase by an extract of Ganoderma lucidum.
AB  - The human aldose reductase inhibitory effects of the methanol extracts of 17
      medicinal and edible mushrooms were examined. Ganoderma lucidum showed the
      highest aldose reductase inhibitory activity compared with the other mushrooms.
      The effect of an ethanol extract of G. lucidum on the galactitol level in the eye
      lens was studied in a galactosemic rat model in vivo. This mushroom significantly
      decreased the galactitol accumulation.

PMID- 19107827
TI  - Quantification of cardiomyocyte contraction based on image correlation analysis.
AB  - Quantification of cardiomyocyte contraction is usually obtained by measuring
      globally cell shortening from the displacement of cell extremities. We developed
      a correlation-based optical flow method, which correlates the whole-cell temporal
      pattern with a precise quantification of the intracellular strain wave at the
      sarcomeres level. A two-dimensional image correlation analysis of cardiomyocytes
      phase-contrast images was developed to extract local cell deformations from
      videomicroscopy time-lapse sequences. Test images, synthesized from known
      intensity displacement fields, were first used to validate the method.
      Intracellular strain fields were then computed from videomicroscopy time-lapse
      sequences of single adult and neonatal cardiomyocytes. The propagation of the
      sarcomeres contraction-relaxation wave during cell contraction has been
      successfully quantified. The time-varying patterns of intracellular displacement
      were obtained accurately, even when cardiomyocyte bending occurred in pace with
      contraction. Interestingly, the characterization of the successive 2D
      displacement fields show a direct quantification of the variation with time of
      intracellular strains anywhere in the cell. The proposed method enables a
      quantitative analysis of cardiomyocyte contraction without requiring wave
      tracking with the use of fluorescent calcium probes. Thus, our algorithmic
      approach provides a fast and efficient tool for analyzing the correlation between
      global cell dynamical behavior and mechanosensitive intracellular processes.

PMID- 19107828
TI  - Loss of surface EWI-2 on CD9 null oocytes.
AB  - CD9, a member of the tetraspanin family, associates with a variety of other
      proteins to form the tetraspanin web. CD9 forms direct and relatively stable
      associations with the immunoglobulin superfamily proteins EWI-2 and EWI-F.
      Deletion of the Cd9 gene results in female infertility since Cd9 null mice
      produce oocytes that fail to fuse. It is thought that the absence of CD9 causes
      the inability of the oocytes to fuse. In this study, we report that the
      expression level of EWI-2 on the Cd9(-/-) oocyte surface is <10% of the wild-type
      level. Hence, the severe reduction in EWI-2 activity may be responsible for the
      loss of fusion ability. An entirely different mutant of CD9, not a deletion but a
      depalmitoylated construct, does not affect in vivo female fertility suggesting
      that the palmitate modification of CD9 is not essential for its putative fusion
      function. Additionally, the level of EWI-2 on the surface of the oocytes from
      these females was comparable to the EWI-2 level on wild-type oocytes. We also
      found that soluble, recombinant EWI-2 binds preferentially to acrosome-reacted
      sperm but the bound EWI-2 does not inhibit sperm-oocyte fusion. Overall, the
      results indicate that deletion of CD9, which is known to have multiple
      associations, may have pleiotropic effects on function that will require further
      dissection.

PMID- 19107829
TI  - Regimented and lifestyle restraint in binge eating disorder.
AB  - OBJECTIVE: This study tested the psychometric properties of two commonly used
      measures of dietary restraint, the Three Factor Eating Questionnaire and the
      Eating Disorder Examination Questionnaire. METHOD: Restraint data from 512
      overweight/obese participants with binge eating disorder (BED) were subjected to
      exploratory and confirmatory factor analyses. RESULTS: Factor analyses of the
      restraint variables indicated a two-factor solution, interpreted as "Regimented"
      and "Lifestyle" restraint. Stepwise regression analyses revealed that Regimented
      restraint was more predictive of eating pathology, whereas Lifestyle restraint
      appeared to be protective of eating problems. Neither type of restraint was
      related to binge eating. Cluster analysis of the restraint dimensions yielded
      three distinct subgroups of patients who differed significantly on several
      important eating- and weight-related features. DISCUSSION: Future research is
      needed to test the significance of these restraint constructs over time in both
      the development of obesity and binge eating problems as well as their treatment.

PMID- 19107830
TI  - Family structure, body mass index, and eating behavior.
AB  - OBJECTIVE: To explore associations between family structure, children's body mass
      index (BMI), and eating behaviors of children and their mothers. METHOD: Fifty
      seven mothers and their children took part in an experimental study. BMI of
      children was measured. Mothers were asked to provide self-report data on
      sociodemographic background, mental health, and eating behaviors about themselves
      and their children. Parent-child-dyads represented their family structure using
      the Family System Test. RESULTS: We found negative associations in typical family
      situations between family hierarchy and children's BMI, mothers' emotional eating
      and mothers' restrained eating. Family cohesion and restrained eating of the
      children were also negatively correlated. We obtained positive associations in
      typical and conflict family situations between family cohesion and external
      eating of the children. DISCUSSION: We found indications that family structure is
      associated with overweight and with eating behavior in children and their
      mothers.

PMID- 19107831
TI  - Energy metabolism and body composition in long-term recovery from anorexia
      nervosa.
AB  - OBJECTIVE: The aim of this study was to determine if energy metabolism and body
      composition differ between women recovered from anorexia nervosa for 2 or more
      years (RAN) and control (C) women. METHOD: Using a cross-sectional design, 16 RAN
      and 18 C women were studied. Respiratory quotient (RQ) and resting energy
      expenditure (REE) were measured using indirect calorimetry and body composition
      using dual energy X-ray absorptiometry. RESULTS: The REE between RAN and C women
      was not significantly different, even when adjusted for body composition.
      However, RAN women had a higher rate of fat oxidation (p = .015), controlling for
      diet and body composition. There were no significant differences between the
      groups for body composition, percent body fat, or percent truncal fat mass.
      DISCUSSION: Although RAN women have a higher rate of fat oxidation, there were no
      significant differences in REE or body composition when compared with C women.

PMID- 19107832
TI  - Zolpidem induced Nocturnal Sleep-Related Eating Disorder (NSRED) in a male
      patient.
AB  - Nocturnal Sleep-Related Eating Disorder (NSRED) is a well-documented sleeping
      disorder where the person is reported to experience bizarre eating behavior
      during sleep. Although various causes are implicated in this disorder, role of
      drugs cannot be ruled out. Here we narrate an interesting rare case report of a
      drug-induced new onset NSRED, where a 45-year-old man on zolipdem performed an
      unexpected and bizarre eating behavior during somnambulistic state, type of which
      has not been reported earlier in the literature. The case falls under even rarer
      category as such behavior in sleep is reported mainly in woman.

PMID- 19107833
TI  - Gender difference in the prevalence of eating disorder symptoms.
AB  - OBJECTIVE: This study examined gender differences in prevalence of eating
      disorder symptoms including body image concerns (body checking or avoidance),
      binge eating, and inappropriate compensatory behaviors. METHOD: A random sample
      of members (ages 18-35 years) of a health maintenance organization was recruited
      to complete a survey by mail or on-line. Items were drawn from the Patient Health
      Questionnaire and the Body Shape Questionnaire. RESULTS: Among the 3,714 women
      and 1,808 men who responded, men were more likely to report overeating, whereas
      women were more likely to endorse loss of control while eating. Although
      statistically significant gender differences were observed, with women
      significantly more likely than men to report body checking and avoidance, binge
      eating, fasting, and vomiting, effect sizes ("Number Needed to Treat") were small
      to moderate. DISCUSSION: Few studies of eating disorders include men, yet our
      findings suggest that a substantial minority of men also report eating disorder
      symptoms.

PMID- 19107834
TI  - Longitudinal examination of maternal psychological control and adolescents' self
      competence as predictors of bulimic symptoms among boys and girls.
AB  - OBJECTIVE: Because bulimia nervosa is a problem among adolescents, it remains
      essential to examine its precursors. The specific etiologic chain investigated in
      this study is such that maternal psychological control first leads to
      adolescents' lowered self-competence, which in turn predicts bulimic symptoms.
      METHOD: Self-report data were collected from 58 boys and 73 girls during sixth,
      seventh, and eighth grades. Participants reported on maternal psychological
      control, self-competence, and bulimic symptoms. RESULTS: Using structural
      equation modeling, we tested our hypothesized longitudinal indirect effects model
      separately for boys and girls. Results indeed indicated that high maternal
      psychological control in sixth grade led to lowered adolescents' self-competence
      in seventh grade, which in turn predicted increased bulimic symptoms in eighth
      grade for both boys and girls. DISCUSSION: This study uncovers one particular
      process wherein a psychologically controlling parenting style affects
      adolescents' development of bulimic symptoms, a finding that may be useful to
      researchers and clinicians.

PMID- 19107835
TI  - Rate of inpatient weight restoration predicts outcome in anorexia nervosa.
AB  - OBJECTIVE: To examine weight restoration parameters during inpatient treatment as
      predictors of outcome in anorexia nervosa (AN). METHOD: Adolescent and adult
      females admitted for inpatient eating disorder treatment were recruited for an
      ongoing longitudinal study. This analysis examined several weight restoration
      parameters as predictors of clinical deterioration after discharge among
      participants with AN. RESULTS: Rate of weight gain was the only restoration
      parameter that predicted year 1 outcome. Clinical deterioration occurred
      significantly less often among participants who gained >or=0.8 kg/week (12/41,
      29%) than those below this threshold (20/38, 53%) (chi(2) = 4.37, df = 1, p =
      .037) and remained significant after adjustment for potential confounders.
      DISCUSSION: Weight gain rate during inpatient treatment for AN was a significant
      predictor of short-term clinical outcome after discharge. It is unclear whether
      weight gain rate exerts a causal effect or is rather a marker for readiness to
      tolerate weight restoration and engage in the recovery process.

PMID- 19107836
TI  - Anorexic self-control and bulimic self-hate: differential outcome prediction from
      initial self-image.
AB  - OBJECTIVE: The study investigated initial self-image (structural analysis of
      social behavior) and its relation to 36-month outcome, among patients with
      anorexia nervosa and bulimia nervosa. Hypotheses were that degree of different
      aspects of self-image would predict outcome in the groups. METHOD: Participants
      were 52 patients with anorexia and 91 with bulimia from a longitudinal
      naturalistic database, and outcome measures included eating disorder and
      psychiatric symptoms and a general outcome index. Stepwise regression was used to
      investigate which self-image variables were related to outcome, and multiple
      regression contrasted the groups directly on each obtained predictor. RESULTS:
      Consistent with hypotheses, in bulimia degree of self-hate/self-love moderately
      predicted outcome, whereas self-control-related variables powerfully predicted
      outcome in anorexia. DISCUSSION: It is important to focus on self-image in the
      treatment of both diagnostic groups, but especially in anorexia nervosa, where
      control-submission interactions between patient and therapist should be handled
      with care.

PMID- 19107837
TI  - Effects of yeast hydrolysate on neuropeptide Y (NPY) and tryptophan hydroxylase
      (TPH) immunoreactivity in rats.
AB  - To investigate the appetite regulation mechanism of low and high molecular weight
      yeast hydrolysate, neuropeptide Y (NPY) and tryptophan hydroxylase (TPH)
      expressions were analyzed in the brains on rats using immunohistochemical method;
      normal diet (control), 0.1 g/kg (BY-1) or 1.0 g/kg (BY-2) of yeast hydrolysate
      below 10 kDa, 0.1 g/kg (AY-1) or 1.0 g/kg (AY-2) of yeast hydrolysate of 10-30
      kDa. Body weight gain was lower in the BY-2 (133.0 g) than in the control (150.1
      g) (p < 0.05). Triacylglyceride, total cholesterol, and LDL-cholesterol levels
      were lower in the BY-2 as compared to control, BY-1 and AY-2 (p < 0.05). NPY
      staining intensities at paraventricular nucleus (PVN) were lower in the BY groups
      (BY-1: 96.1, BY-2: 88.6) as compared to the control (105.6) and AY groups (AY-1:
      110.5, AY-2: 114.1) (p < 0.05). NPY expression at lateral hypothalamic area (LHA)
      was lower in the BY-2 (92.3) than in the control (98.9) (p < 0.05). The BY groups
      (BY-1: 143.9, BY-2: 154.6) had higher TPH staining intensities at dorsal raphe
      (DR) than the AY-2 (115.9) (p < 0.05). In conclusion, the results indicate that
      administering yeast hydrolysate of below 10 kDa to normal diet-fed rats reduced
      body weight gain and serum lipids by altering NPY and TPH expressions.

PMID- 19107838
TI  - Improving target registration accuracy in image-guided neurosurgery by optimizing
      the distribution of fiducial points.
AB  - BACKGROUND: The point-pair method is widely used to register the patient space
      and the image space in image-guided neuro surgery. In this kind of registration,
      the distribution of fiducial points has a great influence on the registration
      accuracy at the target point. METHODS: In this paper we propose the idea of
      target registration accuracy contribution (TRAC) of current fiducial points and
      of candidate fiducial points. Based on these two values, we give an interactive
      method to help the surgeon optimize the distribution of fiducial points so as to
      improve the registration accuracy at the target point. RESULTS: The experiments
      on real patients' data showed that this approach reduced approximately half of
      the registration error at the target point introduced by unsuitable distribution
      of fiducial points. When transferring the optimized distribution to real
      patients, the target registration accuracy obtained from optimization had no
      serious deterioration. CONCLUSION: This study provides a practical approach for
      neurosurgeons to arrange the fiducial points properly on a patient's head.

PMID- 19107839
TI  - Soy-diet has beneficial effects on cardiovascular parameters that are independent
      of its lipid effect in male hypercholesterolemic rats.
AB  - Diet-induced atherosclerosis is lower in animals fed soy protein. The effects of
      various soy components have been extensively studied; however, little is known
      about the effect of crude soybean feeding on hypercholesterolemia-induced
      cardiovascular changes. This study investigated the effect of soy feeding on
      cardiovascular parameters in hypercholesterolemic male rats. Total cholesterol
      (TC), low density lipoprotein (LDL) and high density lipoprotein cholesterol
      (HDL), and triglyceride (TG) were measured. Rats were randomly assigned to
      control, high cholesterol (HC, 2% cholesterol) or HC + soy (HC+S) diets. In the
      HC+S group, rats received HC diet for 10 weeks followed by 2 weeks of soybean
      feeding. Arterial blood pressure, TC, TG, LDL and HDL were measured. TC, TG and
      LDL were higher in HC rats and were not significantly reduced by soybean feeding.
      Soy feeding reversed the HC-induced increase in arterial blood pressure and also
      restored the impaired vascular responses to acetylcholine in isolated aortic
      rings. Pre-incubation of HC+S aortic rings with L-NAME (10(-5) M for 20 min)
      partially reduced the effects of soy on acetylcholine responses, indicating that
      the beneficial vascular effects of dietary soy are partially mediated via nitric
      oxide pathway.

PMID- 19107840
TI  - Triterpene acids isolated from Lagerstroemia speciosa leaves as alpha-glucosidase
      inhibitors.
AB  - The potential antidiabetic activity of ethyl acetate extract of the leaves of
      Lagerstroemia speciosa (LSL) was investigated by alpha-amylase and alpha
      glucosidase inhibition assay. Six pentacyclic triterpenes (oleanolic acid,
      arjunolic acid, asiatic acid, maslinic acid, corosolic acid and 23-hydroxyursolic
      acid) were isolated from LSL. Their structures were determined by spectroscopic
      analysis and their alpha-glycosidase and alpha-amylase inhibitory activities were
      investigated. They exhibited no or weak inhibitory activity against alpha-amylase
      and middle alpha-glucosidase inhibitory activities. Corosolic acid, which shows
      best bioactivity against alpha-glucosidase (IC(50) = 3.53 microg/mL), contributes
      most to the alpha-glucosidase inhibitory activity of EtOAc extract. The kinetics
      of inhibition of corosolic acid was also discussed. Results from this study might
      provide the scientific evidence for LSL for the treatment of diabetes in
      traditional medicine.

PMID- 19107841
TI  - Endogenous FGF-2 is critically important in PTH anabolic effects on bone.
AB  - Parathyroid hormone (PTH) increases fibroblast growth factor receptor-1 (FGFR1)
      and fibroblast growth factor-2 (FGF-2) expression in osteoblasts and the anabolic
      response to PTH is reduced in Fgf2-/- mice. This study examined whether candidate
      factors implicated in the anabolic response to PTH were modulated in Fgf2-/-
      osteoblasts. PTH increased Runx-2 protein expression in Fgf2+/+ but not Fgf2-/-
      osteoblasts. By immunocytochemistry, PTH treatment induced nuclear accumulation
      of Runx-2 only in Fgf2+/+ osteoblasts. PTH and FGF-2 regulate Runx-2 via
      activation of the cAMP response element binding proteins (CREBs). Western blot
      time course studies showed that PTH increased phospho-CREB within 15 min that was
      sustained for 24 h in Fgf2+/+ but had no effect in Fgf2-/- osteoblasts. Silencing
      of FGF-2 in Fgf2+/+ osteoblasts blocked the stimulatory effect of PTH on Runx-2
      and CREBs phosphorylation. Studies of the effects of PTH on proteins involved in
      osteoblast precursor proliferation and apoptosis showed that PTH increased
      cyclinD1-cdk4/6 protein in Fgf2+/+ but not Fgf2-/- osteoblasts. Interestingly,
      PTH increased the cell cycle inhibitor p21/waf1 in Fgf2-/- osteoblasts. PTH
      increased Bcl-2/Bax protein ratio in Fgf2+/+ but not Fgf2-/- osteoblasts. In
      addition PTH increased cell viability in Fgf2+/+ but not Fgf2-/- osteoblasts.
      These data suggest that endogenous FGF-2 is important in PTH effects on
      osteoblast proliferation, differentiation, and apoptosis. Reduced expression of
      these factors may contribute to the reduced anabolic response to PTH in the Fgf2
      /- mice. Our results strongly indicate that the anabolic PTH effect is dependent
      in part on FGF-2 expression.

PMID- 19107842
TI  - Calcification or dedifferentiation: requirement to lock mesenchymal stem cells in
      a desired differentiation stage.
AB  - A current challenge in mesenchymal stem cell (MSC)-based cartilage repair is to
      solve donor and tissue-dependent variability of MSC cultures and to prevent
      chondrogenic cells from terminal differentiation like in the growth plate. The
      aim of this study was to select the best source for MSC which could promise
      stable cartilage formation in the absence of hypertrophy and ectopic in vivo
      mineralization. We hypothesized that MSC from synovium are superior to bone
      marrow- and adipose tissue-derived MSC since they are derived from a joint
      tissue. MSC were characterized by flow cytometry. MSC pellets were cultured under
      chondrogenic conditions and differentiation was evaluated by histology, gene
      expression analysis, and determination of alkaline phosphatase activity (ALP).
      After chondrogenic induction, pellets were transplanted subcutaneously into SCID
      mice. MSC from bone marrow, adipose tissue, and synovium revealed similar
      COL2A1/COL10A1 mRNA levels after chondrogenic induction and were positive for
      collagen-type-X. Bone marrow-derived and adipose tissue-derived MSC showed
      significantly higher ALP activity than MSC from synovium. Low ALP-activity before
      transplantation of pellets correlated with marginal calcification of explants.
      Surprisingly, non-mineralizing transplants specifically lost their collagen-type
      II, but not collagen-type I deposition in vivo, or were fully degraded. In
      conclusion, the lower donor-dependent ALP activation and reduced mineralization
      of synovium-derived heterotopic transplants did not lead to stable ectopic
      cartilage as known from articular chondrocytes, but correlated with fibrous
      dedifferentiation or complete degeneration of MSC pellets. This emphasizes that
      beside appropriate induction of differentiation, locking of MSC in the desired
      differentiation state is a major challenge for MSC-based repair strategies.

PMID- 19107844
TI  - Cytotoxic activity of alkaloids isolated from Stephania rotunda [corrected].
AB  - Three major alkaloids: cepharanthine (1), tetrahydropalmatine (2) and xylopinine
      (3) isolated from Stephania rotunda tuber were investigated for their cytotoxic
      activity in a panel of human cancer cells (HT29, LS174T, SW620 and HepG2) using
      MTT assay. In the present study, cepharanthine (1) exerted potent cytotoxicity
      against colon and hepatoma cancer cell lines with IC(50) values between 2.4 and
      5.3 microM while tetrahydropalmatine (2) and xylopinine (3) displayed weak
      cytotoxicity. In addition, the mutagenic activity of cepharanthine (1) was
      investigated using a modified liquid incubation technique of the
      Salmonella/microsomal assay. This alkaloid (1) was found to be non-mutagenic for
      doses up to 8.2 microM.

PMID- 19107843
TI  - Roles of focal adhesions and fibronectin-mediated cohesion in proliferation of
      confluent fibroblasts.
AB  - Multilayered fibroblast sheets have applications as cell transplants for tissue
      engineering. One way to increase their therapeutic efficacy is to increase cell
      numbers in a graft, but the factors influencing multilayered growth remain poorly
      understood. In this study, we investigated the roles of focal adhesion (FA)
      assembly and intercellular cohesion through fibronectin (FN) in the proliferation
      of normal human fibroblasts at confluence. Density-dependent growth-arrested
      fibroblasts resumed DNA synthesis when cultured in multilayer formation medium
      (MFM) containing transforming growth factor-beta1, ascorbic acid, and serum. This
      proliferation depended on alpha 5 beta 1-integrin-mediated cell-FN-cell
      interactions because blocking them with antibodies inhibited DNA synthesis.
      However, cell-FN-cell cohesion operated well regardless of exposure to MFM,
      judging from several parameters, including FN matrix deposition, activated beta1
      integrin expression, and stress fiber development. Density-arrested cells formed
      few FAs at the cell center. Exposure of the cells to MFM induced the formation of
      vinculin-, paxillin-, and phosphotyrosine-containing FAs throughout the ventral
      cell-surface, indicating ROCK-mediated actomyosin contractile force generation.
      When the assembly of FAs was inhibited with either the ROCK inhibitor Y-27632 or
      the myosin II inhibitor blebbistatin, the up-regulation of DNA synthesis by MFM
      was suppressed. The drugs did not impair FN matrix deposition, activated beta1
      integrin expression, and stress fiber development. Thus, these results indicate
      that the formation of FAs promotes the proliferation of confluent fibroblasts
      with the support of alpha 5 beta 1-integrin-mediated cell-FN-cell cohesion. The
      present findings provide insights into the rational design of high-density
      fibroblast transplants.

PMID- 19107845
TI  - Complement-fixing activity of fulvic acid from Shilajit and other natural
      sources.
AB  - Shilajit has been used traditionally in folk medicine for the treatment of a
      variety of disorders, including syndromes involving excessive complement
      activation. Extracts of Shilajit contain significant amounts of fulvic acid (FA),
      and it has been suggested that FA is responsible for many therapeutic properties
      of Shilajit. However, little is known regarding the physical and chemical
      properties of Shilajit extracts, and nothing is known about their effects on the
      complement system. To address this issue, extracts of commercial Shilajit were
      fractionated using anion exchange and size-exclusion chromatography. One neutral
      (S-I) and two acidic (S-II and S-III) fractions were isolated, characterized and
      compared with standardized FA samples. The most abundant fraction (S-II) was
      further fractionated into three sub-fractions (S-II-1 to S-II-3). The van
      Krevelen diagram showed that the Shilajit fractions are the products of
      polysaccharide degradation, and all fractions, except S-II-3, contained type II
      arabinogalactan. All Shilajit fractions exhibited dose-dependent complement
      fixing activity in vitro with high potency. Furthermore, a strong correlation was
      found between the complement-fixing activity and carboxylic group content in the
      Shilajit fractions and other FA sources. These data provide a molecular basis to
      explain at least part of the beneficial therapeutic properties of Shilajit and
      other humic extracts.

PMID- 19107846
TI  - Zebrafish neurolin-a and -b, orthologs of ALCAM, are involved in retinal ganglion
      cell differentiation and retinal axon pathfinding.
AB  - Neurolin-a and Neurolin-b (also called alcam and nlcam, respectively) are
      zebrafish orthologs of human ALCAM, an adhesion protein of the immunoglobulin
      superfamily with functions in axon growth and guidance. Within the developing
      zebrafish retina, onset and progression of Neurolin-a expression parallels the
      pattern of retinal ganglion cell (RGC) differentiation. By using a morpholino
      based knockdown approach, we show that Neurolin-a (but not Neurolin-b) is
      necessary for a crucial step in RGC differentiation. Without Neurolin-a, a large
      proportion of RGCs fail to develop, and RGC axons are absent or reduced in
      number. Subsequently, Neurolin-a is required for RGC survival and for the
      differentiation of all other retinal neurons. Neurolin-b is expressed later in
      well-differentiated RGCs and is required for RGC axon pathfinding. Without
      Neurolin-b, RGC axons grow in highly aberrant routes along the optic tract and/or
      fail to reach the optic tectum. Thus, the zebrafish Neurolin paralogs are
      involved in distinct steps of retinotectal development.

PMID- 19107847
TI  - Retinal neurogenesis and ontogenetic changes in the visual system of the brown
      banded bamboo shark, Chiloscyllium punctatum (Hemiscyllidae, Elasmobranchii).
AB  - The development of the eye of the oviparous brown banded bamboo shark,
      Chiloscyllium punctatum, was monitored from egg deposition through adulthood. The
      order and timing of retinal cell differentiation were assessed by light and
      transmission electron microscopy. As in other vertebrates, the ganglion cells are
      the first to differentiate, in this case by 81 days post-egg deposition (dpd).
      The order then deviates from what is typically quoted for vertebrates, with the
      Muller and amacrine cells differentiating morphologically around the same time,
      followed by the bipolar cells (101 dpd) and finally the horizontal cells and
      photoreceptors (124 dpd). The neural retina is fully differentiated and synaptic
      connections are formed approximately 1 month prior to hatching, which occurs at
      about 158 dpd. The mature retina is duplex, with a peak rod to cone ratio of
      approximately 12:1. The eye and lens of C. punctatum continue to grow throughout
      life and become less aspherical with growth; the equatorial (nasotemporal) lens
      diameter is 12% larger than the axial (anterior-posterior) lens diameter in
      embryos and 8% larger in adults. Access to developmental stages and the
      protracted gestational period of C. punctatum make it a highly valuable model for
      developmental studies of the visual system. This study also provides an
      evolutionary perspective on retinal neurogenesis in an elasmobranch.

PMID- 19107849
TI  - Inhibitory effects of green tea catechin on the lipid accumulation in 3T3-L1
      adipocytes.
AB  - The aim of the present study was to evaluate the effects of green tea (-)
      epigallocatechin-3-gallate (EGCG) on the depletion of accumulated fat in
      differentiated 3T3-L1 adipocytes. Intracellular lipid accumulation was decreased
      significantly after 24 h of incubation with 10 microm EGCG, while the viability
      of adipocytes was reported to be unaffected. Under the same experimental
      conditions, the amount of glycerol released from cells into the medium was
      increased by 10 microm EGCG. The level of mRNA in the 3T3-L1 adipocytes was
      analysed by quantitative real-time RT-PCR. EGCG notably increased the mRNA level
      of hormone sensitive lipase (HSL), which catalyses the rate-limiting stage in
      hydrolysis of stored triacylglycerol to monoacylglycerol and free fatty acids. In
      conclusion, the experiment produced results which showed that green tea EGCG
      effectively depleted fat accumulation via the stimulation of lipolysis and
      increased HSL gene expression in 3T3-L1 adipocytes. These results may relate to
      the mechanism by which EGCG modulates lipolysis in adipocytes.

PMID- 19107848
TI  - Differential involvement of reactive oxygen species and nucleoside transporters
      in cytotoxicity induced by two adenosine analogues in human prostate cancer
      cells.
AB  - BACKGROUND: Elevated levels of cellular oxidative stress represent a specific
      vulnerability of malignant cells and exposure to cytotoxic drugs is known to
      induce oxidative stress in cancer cells. The effects of two adenosine analogues,
      2-chloroadenosine and 2-chlorodeoxyadenosine, were investigated to assess their
      mechanism of action in prostate cancer cells. METHODS: Androgen-independent and 
      sensitive (PC3 and LNCaP) prostate cancer cells and mouse primary prostate
      cultures were used in the study. Proliferation and cell cycle progression were
      analyzed in the presence of 2-chloroadenosine and 2-chlorodeoxyadenosine.
      Adenosine receptors and nucleoside transporters expression were determined by RT
      PCR. GSH and reactive oxygen species levels were determined by DTNB and DCFH-DA,
      respectively. Nuclear translocation of Nrf2 was assessed by Western blotting.
      RESULTS: 2-Chloroadenosine marginally affected primary prostate cells viability
      whereas it was more potent than 2-chlorodeoxyadenosine in reducing viability and
      increasing apoptosis in both prostate cancer cell lines. Moreover, ROS levels and
      GSH content were markedly affected in PC3 whereas only ROS production was
      increased in LNCaP cells. The antioxidant butylated hydroxytoluene protected PC3
      cells from GSH depletion and reduction in cell viability induced by 2
      chloroadenosine. CONCLUSIONS: 2-Chloroadenosine, but not 2-chlorodeoxyadenosine
      is capable of inducing apoptosis in prostate cancer cells, an effect which may be
      explained at least partially by the capacity of the nucleoside analogue to modify
      ROS and GSH levels. These observations may offer a rationale for the use of 2
      chloroadenosine to improve the clinical efficacy of GSH-dependent antitumor
      drugs.

PMID- 19107850
TI  - Antiproliferative effect of flavonoids and sesquiterpenoids from Achillea
      millefolium s.l. on cultured human tumour cell lines.
AB  - The antiproliferative activities of n-hexane, chloroform, aqueous-methanol and
      aqueous extracts of the aerial parts of the Achillea millefolium aggregate on
      three human tumour cell lines were investigated by means of MTT assays. The
      chloroform-soluble extract exerted high tumour cell proliferation inhibitory
      activities on HeLa and MCF-7 cells, and a moderate effect on A431 cells;
      accordingly, it was subjected to detailed bioactivity-guided fractionation. As a
      result of the multistep chromatographic purifications (VLC, CPC, PLC, gel
      filtration), five flavonoids (apigenin, luteolin, centaureidin, casticin and
      artemetin) and five sesquiterpenoids (paulitin, isopaulitin, psilostachyin C,
      desacetylmatricarin and sintenin) were isolated and identified by spectroscopic
      methods. The antiproliferative assay demonstrated that centaureidin is the most
      effective constituent of the aerial parts of yarrow: high cell growth inhibitory
      activities were observed especially on HeLa (IC(50) 0.0819 microm) and MCF-7
      (IC(50) 0.1250 microm) cells. Casticin and paulitin were also highly effective
      against all three tumour cell lines (IC(50) 1.286-4.76 microm), while apigenin,
      luteolin and isopaulitin proved to be moderately active (IC(50) 6.95-32.88
      microm). Artemetin, psilostachyin C, desacetylmatricarin and sintenin did not
      display antiproliferative effects against these cell lines. This is the first
      report on the occurrence of seco-pseudoguaianolides (paulitin, isopaulitin and
      psilostachyin C) in the Achillea genus.

PMID- 19107851
TI  - Expression of androgen and estrogen related proteins in normal weight and obese
      prostate cancer patients.
AB  - BACKGROUND: Obesity is associated with an aggressive form of prostate cancer and
      with alterations in androgen and estrogen metabolism. We hypothesized that
      changes in components of the sex steroid receptor axis may contribute to the
      clinical aggressiveness of prostate cancer in obese patients. METHODS: A database
      was assembled containing clinical and pathological variables from 539 patients
      treated with radical prostatectomy at a single urban hospital between 1994 and
      2002. Tissue microarrays were constructed from representative patients and
      expression of androgen receptor (AR), PSA, estrogen receptor alpha (ERalpha),
      estrogen receptor beta (ERbeta), and aromatase was examined. RESULTS: Higher BMI
      correlated strongly with black race, the presence of extra-capsular extension,
      and higher pathologic stage. Expression of AR, PSA, ERbeta and aromatase in
      cancerous epithelial cells did not differ according to obesity status. However,
      decreased expression of ERalpha and aromatase was observed in the stromal
      compartment surrounding non-cancerous acini in obese patients. CONCLUSION: We
      confirm the previously reported associations between obesity and aggressive
      clinical and pathologic features in our single-institution, urban teaching
      hospital. In comparing obese versus non-obese patients, there was no difference
      in expression of androgen or estrogen related proteins in cancerous epithelial
      cells. However, there was a down-regulation of ERalpha and aromatase in the
      stroma of obese patients. Our data suggest obesity may cause stromal changes in
      the sex steroid production and signaling pathways which may affect prostate
      cancer growth via intracrine/paracrine mechanisms.

PMID- 19107852
TI  - Genistein suppresses adipogenesis of 3T3-L1 cells via multiple signal pathways.
AB  - Genistein, an isoflavone, was shown to have therapeutic effects for obesity,
      diabetes and cardiovascular diseases. This study investigated the effect and
      underlying mechanism of genistein on adipogenesis in 3T3-L1 preadipocytes.
      Genistein inhibited lipid accumulation and decreased the nonesterified fatty acid
      (NEFA) content of 3T3-L1 on day 6 after the induction of differentiation with
      methylisobutylxanthine, dexamethasone and insulin (MDI). Genistein recovered
      nitric oxide (NO) release suppressed by MDI and the results were consistent with
      the expression of endothelial NO synthase (eNOS) assayed by western blotting.
      Pretreatment with genistein inhibited the phosphorylation of p38 mitogen
      activated protein kinase (p38 MAPK) stimulated with 10 microg/mL of insulin.
      Furthermore, genistein inhibited the expression of fatty acid synthase (FAS) from
      178% of the MDI group to 74%. SB203580, a p38 inhibitor, mimicked the FAS
      inhibition effect of genistein, suggesting that the inhibitory effect of
      genistein on FAS was partially via the p38 pathway. On the other hand, genistein
      abolished the phosphorylation of janus-activated kinase 2 (JAK2) in response to
      MDI. AG490, a JAK2 inhibitor, suppressed the expression of CCAAT/enhancer binding
      protein alpha (C/EBPalpha), a marker of adipocyte differentiation. The findings
      suggest that genistein attenuates the differentiation of 3T3-L1 involving
      multiple signal pathways.

PMID- 19107853
TI  - The effects of methanol extract of Lobaria pulmonaria, a lichen species, on
      indometacin-induced gastric mucosal damage, oxidative stress and neutrophil
      infiltration.
AB  - Lobaria pulmonaria, a lichen species, has been used in traditional medicine for
      the treatment of various diseases. This study was designed to determine the
      gastroprotective effect of the methanol extract of L. pulmonaria in an
      indometacin-induced ulcer model in rats. The results showed that gastric lesions
      were significantly reduced in a dose-dependent manner. Furthermore, the
      administration of indometacin caused a significant decrease in the levels of
      superoxide, glutathione peroxidase and reduced glutathione and an increase in the
      lipid peroxidation level. Administration of the lichen extract, however, produced
      an increase in the levels of these enzymes and a decrease in lipid peroxidation
      levels, although catalase and myeloperoxidase levels were unaffected. The present
      results suggested that Lobaria pulmonaria has a gastroprotective effect, probably
      due to reducing oxidative stress and neutrophil infiltration.

PMID- 19107854
TI  - Antihyperglycemic and antioxidative effects of a herbal formulation of Radix
      Astragali, Radix Codonopsis and Cortex Lycii in a mouse model of type 2 diabetes
      mellitus.
AB  - There is emerging evidence that the generation of reactive oxygen species (ROS),
      which leads to dysfunction of pancreatic beta-cells, is a major factor in the
      development of type 2 diabetes mellitus. Antioxidation is one of the therapeutic
      strategies to overwhelm the imbalance in ROS production. In this study, a herbal
      formulation SR10, comprising Radix Astragali, Radix Codonopsis and Cortex Lycii,
      was examined for its antidiabetic and antioxidative effects using the diabetic
      +db/+db mouse model. The results showed that SR10 was effective in decreasing the
      blood glucose level in chronic treatment by improving beta-cell function. The
      activities and expression of antioxidant enzymes, catalase and superoxide
      dismutase, were up-regulated when treated with SR10. Moreover, SR10 treatment did
      not exhibit any toxic effect to the host.

PMID- 19107855
TI  - Coronary vasodilator activity of vulgarenol, a sesquiterpene isolated from
      Magnolia grandiflora, and its possible mechanism.
AB  - The aim of this study was to investigate the biodynamic effects of vulgarenol, a
      sesquiterpene isolated from Magnolia grandiflora flower petals and its possible
      mechanism on the Langendorff isolated and perfused heart model. Vulgarenol (5
      microm) caused a statistically significant decrease in coronary vascular
      resistance (15.21 +/- 6.00 dyn s cm(-5) vs 36.80 +/- 5.01 dyn s cm(-5), control
      group), increased nitric oxide release (223.01 +/- 8.76 pmol/mL vs 61.00 +/-
      12.00 pmol/mL, control group) and cyclic guanosine monophosphate accumulation in
      left ventricular tissue samples (142.17 +/- 8.41 pmol/mg of tissue vs 43.94 +/-
      5.00 pmol/mg of tissue, control group). Pre-treatment with 3 microm gadolinium
      chloride hexahydrate, 100 microm N(omega)-nitro-L-arginine methyl ester
      hydrochloride, and 10 microm 1H-[1,2,4]oxadiazolo[4,2-a]quinoxalin-1-one
      significantly abolished the vulgarenol-induced coronary vascular resistance
      decrease, nitric oxide increased release and cGMP accumulation in left
      ventricular tissue samples. The results support the fact that nitric oxide and
      cyclic guanosine monophosphate are likely involved in the endothelium-dependent
      coronary vasodilation.

PMID- 19107856
TI  - Virtual in vivo biopsy map of early prostate neoplasm in TRAMP mice by MRI.
AB  - BACKGROUND: The noninvasive, early detection of Prostate Intraepithelial
      Neoplasia (PIN), a precancerous neoplasia of the prostate, would be highly
      desirable. In our experiments, we used TRAMP mice to model PIN in the range of
      grade 1 through grade 4. METHODS: Contrast enhanced pixel-by-pixel R1 mapping of
      the prostate was used to detect areas with the different prostate neoplasia
      grades. After anesthesia, Gd(ABE-DTTA) was injected I.V. A series of MRI images
      with varying TI were then acquired to create R1 maps in a 2 mm transversal
      tomographic slice that included the prostate. After euthanasia and the excision
      of the prostate, a 2 mm slice, corresponding to the tomographic slice, was
      selected and prepared for histological analysis. The microscopic sections of this
      slice were scanned and analyzed along with the R1 maps. The R1 values were
      normalized to that measured in muscle tissue in each individual mouse to account
      for possible variations among the mice in contrast agent uptake (R1(norm)). The
      R1(norm) values and the histological grades in the corresponding areas were
      correlated. RESULTS: A significant difference was found between the R1(norm)
      values measured in areas with grade 1-2 versus those observed in areas with
      grades 3-4. Also, a significant correlation was found between the area size of
      the ROIs differentiated by MRI, and those determined by histology. CONCLUSION:
      This method has the potential for early noninvasive detection of developing
      prostate cancer.

PMID- 19107857
TI  - Bioassay-guided separation of citreorosein and other oestrogenic compounds from
      Polygonum cuspidatum.
AB  - Citreorosein was isolated from P. cuspidatum as a new oestrogenic compound,
      together with emodin and its glucoside, by silica gel column chromatography and
      preparative high-performance liquid chromatography sequentially. Oestrogenic
      activity was determined by a recombinant yeast assay.

PMID- 19107858
TI  - Apoptosis inducement of bigelovin from Inula helianthus-aquatica on human
      Leukemia U937 cells.
AB  - Inula helianthus-aquatica C. Y. Wu is a traditional medicinal plant used to treat
      some cancers in folk herbal medicine of Yunnan, China. Bigelovin, a sesquiterpene
      lactone isolated from this herb, potently inhibits the growth of a panel of eight
      cancer cell lines, especially in human monoblastic leukemia U937 cells with an
      IC(50) value of 0.47 microM. Characteristic morphological features of apoptosis
      were observed in U937 cells treated with bigelovin. Annexin V and nuclear DNA
      content distribution assays showed that the percentage of Annexin V positive
      cells increased to 8.86% (24 h) with 1 microM bigelovin treatment, and cells
      treated with bigelovin at this concentration apparently arrested at G(0)/G(1)
      phase compared with the control. These data suggested that cytotoxic effect of
      bigelovin on U937 cells involves induction of apoptosis, and the cell cycle is
      arrested at G(0)/G(1) phase.

PMID- 19107859
TI  - Stimulation of osteoblastic differentiation and inhibition of interleukin-6 and
      nitric oxide in MC3T3-E1 cells by pomegranate ethanol extract.
AB  - In this experiment, we studied the effects of pomegranate fruit extract (PE) on
      the function of osteoblastic MC3T3-E1 cells and the production of local factors
      in osteoblasts. PE (16 approximately 250 microg/ml) significantly increased the
      growth of MC3T3-E1 cells (P < 0.05). Moreover, PE (50 microg/ml) caused a
      significant elevation of alkaline phosphatase (ALP) activity and collagen content
      in the cells. We then examined the effect of PE on the TNF-alpha-induced
      production of interleukin-6 (IL-6) and nitric oxide (NO) in osteoblasts.
      Treatment with PE (10 approximately 50 microg/ml) decreased the TNF-alpha (10(
      10) M)-induced production of IL-6 and NO in osteoblasts.

PMID- 19107860
TI  - In vitro anti-adhesive activity of green tea extract against pathogen adhesion.
AB  - Camellia sinensis polysaccharide has been reported to possess anti-adhesive
      activity against pathogens. The present study was designed to investigate whether
      hot water extracts obtained from green tea leaves might inhibit pathogen adhesion
      to human or mouse cell lines. Green tea extract-4 (CSI-4) with the maximum yield
      of 4% (w/v) is composed of a major proportion of carbohydrates containing 40%
      uronic acids, but lack of catechins. It showed strong inhibitory activities
      against hemagglutination mediated by pathogens Helicobacter pylori,
      Propionibacterium acnes and Staphylococcus aureus with the minimum inhibitory
      concentrations of 0.01-0.5 mg/mL. CSI-4 further demonstrated an inhibitory effect
      on the adhesion of these pathogens to host cell lines with the IC(50) values (50%
      inhibition of adhesion) of 0.14-2.3 mg/mL. It exhibited the highest activity
      against P. acnes, but no inhibitory effects were observed against Lactobacillus
      acidophilus, Bifidobacterium bifidum, Escherichia coli, or Staphylococcus
      epidermidis. Our results suggest that CSI-4 may exert a selective anti-adhesive
      effect against certain pathogenic bacteria with no adverse effects against
      beneficial or commensal bacteria.

PMID- 19107861
TI  - Bcl-2 mediated modulation of vascularization in prostate cancer xenografts.
AB  - PURPOSE: We previously demonstrated that Bcl-2 overexpression enhances the
      radiation resistance of PC-3 human prostate cancer cells and xenografts by
      inhibiting apoptosis, increasing proliferation, and promoting angiogenesis. To
      further elucidate the relationship between Bcl-2 expression and the angiogenic
      potential of PC-3-Bcl-2 cells, tumorigenicity, angiogenesis, and
      lymphangiogenesis were evaluated and compared in a Bcl-2 overexpressing clone in
      vitro and in vivo. EXPERIMENTAL DESIGN: Human prostate cancer cells over
      expressing Bcl-2 were studied in vitro and in vivo to determine the angiogenic
      and lymphangiogenic properties of these cells. RESULTS: Increased Bcl-2
      expression enhanced the tumorigenicity of prostate cancer xenografts. It also
      enhanced the expression and secretion of key angiogenic and lymphangiogenic
      factors that stimulated the synthesis of CD31-positive blood vessels and LYVE-1
      positive lymphatics. Specifically, the increased angiogenic and lymphangiogenic
      potential correlated with increased serum levels of basic fibroblast growth
      factor (bFGF), interleukin 8 (CXCL8), and matrix metalloproteinase (MMP 9). In
      vitro analysis demonstrated that Bcl-2 expressing tumor cells secreted bFGF and
      vascular endothelial growth factor (VEGF) into culture supernatants. Microarray
      analysis of Bcl-2 expressing PC-3 cells demonstrated increased transcription of
      genes involved in metabolism, such as interleukins, growth factors, tumor
      necrosis factors (TNF) family members, and peptidases. CONCLUSIONS: Together,
      these results demonstrate that Bcl-2 can regulate tumoral angiogenesis and
      lymphangiogenesis and suggest that therapy targeted at Bcl-2 expression,
      angiogenesis, and lymphangiogenesis may synergistically modulate tumor growth and
      confirm that Bcl-2 is a pivotal target for cancer therapy.

PMID- 19107862
TI  - Antiretroviral activity of fucoidans extracted from the brown seaweed Adenocystis
      utricularis.
AB  - Treatment of human immunodeficiency virus type 1 (HIV-1, causative agent of AIDS)
      infection represents a major challenge in antiviral therapeutics. Many
      difficulties are associated with the treatment, including toxicity, resistance
      and high costs. Taking this into account, research for novel compounds able to
      overcome these limitations is needed. Sulfated polysaccharides appear to be
      interesting, given their abundance as components of seaweeds. Herein, a series of
      fractions obtained from the brown seaweed Adenocystis utricularis was analysed
      for in vitro anti-HIV-1 activity. These fractions, which have anti-herpes simplex
      virus activity, were determined previously to belong to the family of fucoidans,
      sulfated polysaccharides obtained from the cell walls of brown seaweeds. Assays
      in human PBMC primary cell culture demonstrated that two of the five fractions
      analysed had potent anti-HIV-1 activity both against WT and drug-resistant HIV-1
      strains. For active fractions, it was also shown that the inhibitory effect was
      not due to an inactivating effect on the viral particle (i.e. no virucidal
      activity was detected) but rather to a blockade of early events of viral
      replication. Given these encouraging results, these seaweed-derived fractions
      appear as good candidates for further studies on their potential for in vivo
      therapy and/or prophylaxis of HIV-1 infection.

PMID- 19107863
TI  - Antiinflammatory and antinociceptive activities of gossypin and procumbentin-
      cyclooxygenase-2 (COX-2) inhibition studies.
AB  - In the present study the antiinflammatory and antinociceptive activities of a few
      selected flavonoids were investigated. Procumbentin, gossypin, chrysin and
      methylhespiridin were studied for antiinflammatory and antinociceptive activities
      using in vitro enzymatic assays and in animal models utilizing acetic acid
      induced writhing in mice and hind paw edema in rats. In vitro studies were
      performed using TMPD (NNN'N'-tetramethyl-p-phenylene diamine) and oxygraphic
      methods for COX-1 (cyclooxygenase-1), COX-2, 5-LOX (5-lipoxygenase) and 15-LOX.
      Gossypin and procumbentin showed COX-2 inhibitory activity and exhibited IC(50)
      (COX-2/COX-1) ratios of 0.14 and 0.11, respectively. None of the flavonoids
      tested in this study showed LOX inhibitory activity. Four groups were studied for
      each test compound following intraperitoneal (i.p.) administration of doses of
      10, 30 and 100 mg/kg. Antiinflammatory activity was measured by the carrageenin
      induced rat hind paw edema model and antinociceptive activity by acetic acid
      induced writhing. Procumbentin and gossypin showed antinociceptive activity at
      the 100 mg/kg dose. Gossypin showed antiinflammatory activity at doses of 10, 30,
      100 mg/kg. Procumbentin and gossypin exhibited COX-2 inhibitory activity when
      tested by in vitro methods. Procumbentin and gossypin showed antinociceptive, and
      gossypin showed antiinflammatory, activities.

PMID- 19107864
TI  - Selective organic synthesis through generation and reactivity control of hyper
      coordinate metal species.
AB  - This paper is a review of my 40 years of research at Kyoto, Sagamihara, and
      Yokohama, all based on the generation of hyper-coordinate metal species such as
      ate complexes and pentacoordinate silicates. The topics are: (i) carbenoid
      reagents for carbon-carbon bond-forming reactions, (ii) nucleophilic substitution
      at acetal carbons using aluminate reagents, (iii) preparation of magnesium
      enolates and its reaction with nitriles, (iv) Cr(II) reagents for reduction of
      organic halides and highly selective carbon-carbon bond formation, (v) organic
      synthesis with organosilion reagents/fluoride ions, (vi) cross-coupling reaction
      of organosilicon compounds, and (vii) silicon-based conjugate addition to
      alpha,beta-unsaturated carbonyl acceptors.

PMID- 19107865
TI  - Phase-vanishing methods based on fluorous phase screen: a simple way for
      efficient execution of organic synthesis.
AB  - The phase-vanishing (PV) method is based on spontaneous reaction controlled by
      diffusion of reagents into fluorous media, such as perfluorohexanes (FC-72) and
      polyperfluoroethers. Thus, the original PV reaction utilizes a triphasic test
      tube method composed of a bottom reagent phase, a middle fluorous phase, and a
      top substrate phase. In such a triphasic system, the fluorous phase acts as a
      liquid membrane to transport the bottom reagents to the top organic phase
      containing substrates. In the end, the bottom layer disappears and two phases
      remain. Since the first demonstration of the PV method by bromination of alkenes
      with molecular bromine, a number of applications have been developed thus far.
      These include halogenation of alcohols with SOBr(2) and PBr(3), demethylation of
      methoxyarenes with BBr(3), cyclopropanation of alkenes by CH(2)I(2)-AlEt(3), and
      Friedel-Crafts acylation of aromatic compounds with SnCl(4). A fluorous triphasic
      U-tube method is effective for chlorination of alcohols based on lighter (less
      dense) reagents such as SOCl(2) and PCl(3). A system using a solution containing
      reagents as a bottom phase is useful for oxidation with m-CPBA, which may be
      defined as a new category for the "extractive PV" method. Recent advances include
      a "quadraphasic" PV method, in which an aqueous "scavenger" phase is added to the
      original triphasic PV method to remove acidic by-products.

PMID- 19107866
TI  - From cellulosomes to cellulosomics.
AB  - Cellulosomes are intricate multienzyme systems produced by several cellulolytic
      bacteria, the first example of which was discovered in the anaerobic thermophilic
      bacterium, Clostridium thermocellum. Cellulosomes are designed for efficient
      degradation of plant cell wall polysaccharides, notably cellulose--the most
      abundant renewable polymer on earth. The component parts of the multicomponent
      complex are integrated by virtue of a unique family of integrating modules, the
      cohesins and the dockerins, whose distribution and specificity dictate the
      overall cellulosome architecture. A full generation of research has elapsed since
      the original publications that documented the cellulosome concept. In this
      review, we provide a personal account on the discovery process, while describing
      how divergent cellulosome systems were identified and investigated, culminating
      in the collaboration of several labs worldwide to tackle together the challenging
      field of cellulosome genomics and metagenomics.

PMID- 19107867
TI  - Metabolism of tetrahydrobiopterin: its relevance in monoaminergic neurons and
      neurological disorders.
AB  - (6R)-L-erythro-5,6,7,8-tetrahydrobiopterin (BH4) is an essential cofactor for
      aromatic amino acid hydroxylases, such as phenylalanine hydroxylase (PAH),
      tyrosine hydroxylase (TH), tryptophan hydroxylase, and nitric oxide synthase,
      which catalyze physiologically important reactions in mammals. The biosynthesis
      and metabolism of BH4 is usually studied mostly in the liver and only slightly in
      the brain, as the BH4 level in the liver is relatively high because BH4 is
      required for the reaction of PAH. We found that GTP (guanosine triphosphate)
      cyclohydrolase I, an enzyme for the biosynthesis of BH4, is a causative gene for
      DOPA (3,4-dihydroxyphenylalanine)-responsive dystonia (also called Segawa's
      disease), and that partial deficiency of BH4 leads to the dysfunction of the
      nigrostriatal dopaminergic neurons without hyperphenylalaninemia. We analyzed BH4
      deficient mice that were produced by disruption of a BH4-synthesizing gene by a
      gene-knockout technique. We found that the protein amount of TH was highly
      dependent on the amount of BH4, especially in nerve terminals. Our research
      suggests that BH4 metabolism in the brain should be different from that in the
      liver, and that altered metabolism of BH4 should lead to neuropsychiatric
      disorders including Parkinson's disease.

PMID- 19107868
TI  - Intra- and intermolecular amidation of C-C unsaturated bonds through palladium
      catalyzed reactions of carbamoyl derivatives.
AB  - Toward concise access to functionalized amides and lactams, palladium-catalyzed
      amidations of alkynes and alkenes with formamide derivatives were developed.
      Cyanoformamides having an alkynyl group were found to undergo intermolecular
      cyanoamidation in the presence of palladium catalyst to afford alpha-alkylidene
      lactams. Whereas, when cyanoformamides that possess a 1,1-disubstituted alkenyl
      group were used as starting materials, alpha,alpha-disubstituted lactams were
      obtained. The latter reaction was extended to enantioselective transformation by
      utilizing optically active phosphoramidites as ligand. Furthermore,
      chloroformamides having a 1,1,2-trisubsituted alkenyl group were found to give
      alpha-vinyl-lactams in the presence of palladium catalyst, base and silver salt.
      Additionally, formal intermolecular hydroamidation of alkenes was performed
      through one-pot hydroboration-carbamoylation sequence.

PMID- 19107869
TI  - Development of a three-dimensional culture model of prostatic epithelial cells
      and its use for the study of epithelial-mesenchymal transition and inhibition of
      PI3K pathway in prostate cancer.
AB  - BACKGROUND: Appropriate 3D culture models of human prostatic epithelial cells
      resembling normal growth pattern and architecture of prostate gland and its
      malignant development are scarce. METHODS: Here, we optimized the 3D culture
      conditions of the immortalized non-transformed human prostatic epithelial cell
      line BPH-1 in Matrigel and developed a 3D culture model closely mimicking
      prostatic glandular structure. RESULTS: Our results showed that BPH-1 cells
      cultured in Matrigel formed acinus-like spheroids with lumen formation and
      polarized differentiation. To establish an androgen-stimulated differentiation in
      AR-negative BPH-1, we generated AR-transduced BPH-1 cells, which displayed
      androgen-induced secretory differentiation and growth suppression in 3D culture.
      We also evaluated the spheroid forming capacity of tumorigenic derivative BPH
      1(CAFTD) sublines in 3D culture and their responses to PI3K inhibitor LY294002.
      Results showed that these tumorigenic BPH-1(CAFTD) sublines did not exhibit
      polarized differentiation in Matrigel culture. Interestingly, polarization could
      be restored by LY294002 treatment of BPH-1(CAFTD1) but not of BPH-1(CAFTD3)
      subline. Finally, we employed this 3D culture model to examine the significance
      of an EMT-regulatory transcription factor Snail in prostate cancer development by
      its stable transduction into BPH-1 cells. Results showed that BPH-1-Snail cells
      lost their spheroid forming capacity and exhibited an invasive phenotype.
      CONCLUSIONS: Taken together, we established a 3D culture model of human prostatic
      epithelial cells with structural and functional relevance to normal prostate
      gland and prostate cancer development and also demonstrated that this 3D model
      might be useful to assess the ability of drugs to restore differentiation as a
      potential surrogate measure of efficacy for prostate cancer therapy.

PMID- 19107870
TI  - Cell biochemistry and function and the integration of biomedical research
      (location, location, location).

PMID- 19107871
TI  - Protective effect of aminoguanidine against oxidative stress and bladder injury
      in cyclophosphamide-induced hemorrhagic cystitis in rat.
AB  - Cyclophosphamide (CP) is an antineoplastic agent that is used for the treatment
      of many neoplastic diseases. Hemorrhagic cystitis (HC) is a major dose limiting
      side effect of CP. Recent studies show that aminoguanidine, an inhibitor of
      inducible nitric oxide synthase is a potent antioxidant and prevents changes
      caused by oxidative stress such as depletion of antioxidant activity and tissue
      injury. The purpose of the study is to investigate the effect of aminoguanidine
      on parameters of oxidative stress, antioxidant enzymes and bladder injury caused
      by CP. Adult male rats were randomly divided into four groups. Control rats were
      administered saline; the AG control group received 200 mg/kg body wt of
      aminoguanidine; The CP group received a single injection of CP at the dose of 150
      mg/kg body wt intraperitoneally. The CP + AG group received aminoguanidine (200
      mg/kg body wt) intraperitoneally 1 h before the administration of CP. The rats
      were sacrificed 16 h after CP/saline administration. The bladder was used for
      light microscopic studies and biochemical studies. The markers of oxidative
      damage including protein carbonyl content, protein thiol, malondialdehyde and
      conjugated dienes were assayed in the homogenates along with the activities of
      the antioxidant enzymes, superoxide dismutase, glutathione peroxidase, catalase,
      and glutathione reductase and glutathione S transferase. In the bladders of CP
      treated rats edema of lamina propria with epithelial and sub-epithelial
      hemorrhage was seen. All the parameters of oxidative stress that were studied
      were significantly elevated in the bladders of CP treated rats. The activities of
      the antioxidant enzymes were significantly lowered in the bladders of CP treated
      rats. Aminoguanidine pretreatment prevented CP-induced oxidative stress, decrease
      in the activities of anti-oxidant enzymes and reduced bladder damage. The results
      of the present study suggest the antioxidant role for aminoguanidine in CP
      induced bladder damage.

PMID- 19107872
TI  - Effects of short chain fatty acids on effector mechanisms of neutrophils.
AB  - Short chain fatty acids (SCFAs) are metabolic by products of anaerobic bacteria
      fermentation. These fatty acids, despite being an important fuel for colonocytes,
      are also modulators of leukocyte function. The aim of this study was to evaluate
      the effects of SCFAs (acetate, propionate, and butyrate) on function of
      neutrophils, and the possible mechanisms involved. Neutrophils obtained from rats
      by intraperitoneal lavage 4 h after injection of oyster glycogen solution (1%)
      were treated with non toxic concentrations of the fatty acids. After that, the
      following measurements were performed: phagocytosis and destruction of Candida
      albicans, production of ROS (O(2)(*-), H(2)O(2), and HOCl) and degranulation.
      Gene expression (p47(phox) and p22(phox)) and protein phosphorylation (p47(phox))
      were analyzed by real time reverse transcriptase chain reaction (RT-PCR) and
      Western blotting, respectively. Butyrate inhibited phagocytosis and killing of C.
      albicans. This SCFA also had an inhibitory effect on production of O(2)(*-),
      H(2)O(2), and HOCl by neutrophils stimulated with PMA or fMLP. This effect of
      butyrate was not caused by modulation of expression of NADPH oxidase subunits
      (p47(phox) and p22(phox)) but it was in part due to reduced levels of p47(phox)
      phosphorylation and an increase in the concentration of cyclic AMP. Acetate
      increased the production of O(2)(*-) and H(2)O(2) in the absence of stimuli but
      had no effect on phagocytosis and killing of C. albicans. Propionate had no
      effect on the parameters studied. These results suggest that butyrate can
      modulate neutrophil function and thus could be important in inflammatory
      neutrophil-associated diseases.

PMID- 19107873
TI  - KAI1/CD82 decreases Rac1 expression and cell proliferation through PI3K/Akt/mTOR
      pathway in H1299 lung carcinoma cells.
AB  - Although the KAI1/CD82 protein has been reported to inhibit cell metastasis in
      many studies, its mechanism of action has not yet been fully elucidated. In the
      present study, we investigated the possible effects of KAI1/CD82 on the
      metastatic phenotype in H1299 lung carcinoma cells. These studies were based on
      the pivotal role that the acquisition of motile phenotype plays on the initial
      steps of metastasis. KAI1/CD82-mediated morphological changes were observed using
      phase contrast microscopy. We report here, that a KAI1/CD82-induced phenotypic
      change was involved in the decrease of Rac1 expression and GTPase activity.
      However, we found that KAI1/CD82 did not regulate Rac1 mRNA levels. This suggests
      the existence of another regulatory mechanism of Rac1 protein maturation or
      activation. To identify the signaling pathway of Rac1 regulation, we investigated
      the PI3K/Akt/mTOR pathway, since the PI3K/Akt pathway regulates Rac1 activation
      and mTOR is known to play a regulatory role in protein translation. H1299/CD82
      transfectants showed lower mTOR expression and cell growth than the control
      group. The data obtained from this study suggested that KAI1/CD82 decreased the
      metastatic phenotype of H1299 lung carcinoma cells by down-regulating Rac1
      expression through the PI3K/Akt/mTOR pathway.

PMID- 19107874
TI  - Oxidative stress resistance through blocking Hsp60 translocation followed by
      SAPK/JNK inhibition in aged human diploid fibroblasts.
AB  - The stress-activated protein kinase/c-Jun N-terminal kinase (SAPK/JNK) pathway is
      a well-known senescence-related stress activated protein kinase. Multiple
      environmental stresses induce programmed cell death, such as apoptosis. Normal
      human diploid fibroblast (HDF) cells have a limited life span in vitro, halting
      proliferation after a fixed number of cell divisions. Aged passage HDF showed
      resistance to oxidative stress involving heat shock proteins (Hsp60) through a
      mechanism involving the translocation of Hsp60 from the mitochondria to the
      cytosol. The present study showed that the translocation of Hsp60 from the
      mitochondria to the cytosol followed by high levels of p-SAPK/JNK activation as a
      result of oxidative stress was observed in the young cells only. The inhibition
      of SAPK/JNK activation by SP600125 under oxidative stress almost completely
      blocked the translocation of Hsp60 in both young and aged cells. This suggests
      that aged HDF cells are resistant to oxidative stress by blocking the
      translocation of Hsp60 from the mitochondria to the cytosol followed by SAPK/JNK
      inhibition. Overall, the mechanism of resistance by oxidative stress in aged
      cells is induced by blocked of the translocation of Hsp60 followed by SAPK/JNK
      inactivation.

PMID- 19107875
TI  - Evidence that L-glutamine is better than L-alanine as gluconeogenic substrate in
      perfused liver of weaned fasted rats submitted to short-term insulin-induced
      hypoglycaemia.
AB  - Gluconeogenesis in livers from overnight fasted weaned rats submitted to short
      term insulin-induced hypoglycaemia (IIH) was investigated. For this purpose, a
      condition of hyperinsulinemia/hypoglycaemia was obtained with an intraperitoneal
      (ip) injection of regular insulin (1.0 U kg(-1)). Control group (COG group)
      received ip saline. The studies were performed 30 min after insulin (IIH group)
      or saline (COG group) injection. The livers from IIH and COG rats were perfused
      with L-alanine (5 mM), L-lactate (2 mM), L-glutamine (10 mM) or glycerol (2 mM).
      Hepatic glucose, L-lactate and pyruvate production from L-alanine was not
      affected by IIH. In agreement with this result, the hepatic ability in producing
      glucose from L-lactate or glycerol remained unchanged (IIH group vs. COG group).
      However, livers from IIH rats showed higher glucose production from L-glutamine
      than livers from COG rats and, in the IIH rats, the production of glucose from L
      glutamine was higher than that from L-alanine. The higher glucose production in
      livers from the IIH group, when compared with the COG group was due to its
      entrance further on gluconeogenic pathway. Taken together, the results suggest
      that L-glutamine is better than L-alanine, as gluconeogenic substrate in livers
      of hypoglycaemic weaned rats.

PMID- 19107876
TI  - TGFbeta3 and loading increases osteocyte survival in human cancellous bone
      cultured ex vivo.
AB  - The goal of this study was to assess the effect of the addition of TGFbeta(3),
      alone or in combination with loading, on the survival of osteocytes in 3D human
      explant cancellous bone during long-term culture in an ex vivo loading
      bioreactor. Human cancellous bone explants were cultured for up to 14 days with
      or without TGFbeta(3) (15 ng ml(-1)) and with or without loading (300 cycles, at
      1 Hz, producing 4000 microstrain). Bone core response was visualized using
      undecalcified histology with morphological methods after embedding with Technovit
      9100 New resin. Histological examination revealed normal gross level bone
      structure with or without the application of load or the addition of TGFbeta(3).
      The viability of the osteocytes within the bone was assessed by lactate
      dehydrogenase (LDH) activity. We demonstrate that this ex vivo loading bioreactor
      is able to maintain a high percentage (over 50%) of viable osteocytes throughout
      the bone explants after 14 days in ex vivo culture. Further to this, the
      combination of daily loading and TGFbeta(3) administration produced superior
      osteocyte survival at the core centres when compared to loading or TGFbeta alone.

PMID- 19107877
TI  - Protective action of indole-3-acetic acid on induced hepatocarcinoma in mice.
AB  - In this study, we report the protective effects of IAA on diethylnitrosamine
      (DEN)-induced hepatocarcinogenesis. BALB/c mice received daily IAA at 50 (T(50)),
      250 (T(250)), and 500 (T(500)) mg Kg(-1) per body mass by gavage for 15 days. At
      day 15, animals were administered DEN and sacrificed 4 h later. Alanine
      aminotransferase (ALT) and aspartate aminotransferase (AST) were analyzed in
      sera. In addition, hepatomorphologic alterations, activity of superoxide
      dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), and glutathione
      reductase (GR), gene expression of antioxidant enzymes and DNA integrity were
      evaluated in the liver. IAA administration did not show any alterations in any of
      the parameters available, except for a reduction of the gene expression for
      antioxidant enzymes by 55, 56, 27, and 28% for SOD, CAT, GPx, and GR upon T(500),
      respectively compared with the control. Several hepatic alterations were observed
      by DEN exposure. Moreover, IAA administration at 3 doses was shown to provide a
      total prevention of the active reduction of CAT and GR induced by DEN exposure
      compared with the control. IAA at T(500) was shown to give partial protection
      (87, 71, 57, and 90% for respectively SOD, CAT, GPx, and GR) on the down
      regulation of the enzymes induced by DEN and this auxin showed a partial
      protection (50%) on DEN-induced DNA fragmentation for both parameters when
      compared to DEN alone. This work showed IAA hepatocarcinogenesis protection for
      the first time by means of a DEN-protective effect on CAT and GR activity, and by
      affecting antioxidant gene expression and DNA fragmentation.

PMID- 19107878
TI  - How applicable is the general adaptation syndrome to the unicellular Tetrahymena?
AB  - Hormone receptors, hormones and signal transduction pathways characteristic of
      higher vertebrates can be observed also in the unicellular Tetrahymena. Previous
      work showed that stress conditions (starvation, high temperature, high salt
      concentration, formaldehyde or alcohol treatment) elevated the intracellular
      level of four hormones (ACTH, endorphin, serotonin and T(3)). Here, the effect of
      other stressors (CuSO4 poisoning, tryptophan hydroxylase inhibitor
      parachlorophenylalanine (PCPA) treatment) on the same and other hormones
      (epinephrine, insulin, histamine) was studied, using immunocytochemistry and flow
      cytometric analysis. It was found, that each effect increased the intracellular
      hormone contents, but some hormones (histamine, T(3)) were less reactive. Insulin
      -which is a life-saving factor for Tetrahymena--itself provoked elevation of
      hormone amounts in association with a stressor, further increased the level of
      hormones. It was concluded that the ancestor of Selye's General Adaptation
      Syndrome (GAS) can be found already at unicellular level, and this possibly has a
      life saving function.

PMID- 19107879
TI  - Effects of arachidonic acid and docosahexaenoic acid on differentiation and
      mineralization of MC3T3-E1 osteoblast-like cells.
AB  - Osteoblasts in culture can differentiate into mature mineralizing osteoblasts
      when stimulated with osteogenic agents. Clinical trials and in vivo animal
      studies suggest that specific polyunsaturated fatty acids (PUFAs) may benefit
      bone health. The aim of this study was to investigate whether arachidonic acid
      (AA) and docosahexaenoic acid (DHA) affect osteogenesis in osteoblasts and the
      transdifferentiation into adipocytes. Results from this study show that long-term
      exposure to AA inhibited alkaline phosphatase (ALP) activity in these cells,
      which might be prostaglandin E(2) (PGE(2))-mediated. DHA exposure also inhibited
      ALP activity which was evident after both short- and long-term exposures. The
      mechanism whereby DHA inhibits ALP activity is not clear and needs to be
      investigated. Although long-term exposure to PUFAs inhibited ALP activity, the
      mineralizing properties of these cells were not compromised. Furthermore, PUFA
      exposure did not induce adipocyte-like features in these cells as evidenced by
      the lack of cytoplasmic triacylglycerol accummulation. More research is required
      to elucidate the cellular mechanisms of action of PUFAs on bone.

PMID- 19107880
TI  - The vitamin D receptor agonist elocalcitol inhibits IL-8-dependent benign
      prostatic hyperplasia stromal cell proliferation and inflammatory response by
      targeting the RhoA/Rho kinase and NF-kappaB pathways.
AB  - BACKGROUND: Benign prostatic hyperplasia (BPH) is characterized by an important
      inflammatory component. Stimulation of human prostate stromal cells from BPH
      tissues with proinflammatory cytokines leads to secretion of IL-8, a chemokine
      involved in BPH pathogenesis. The vitamin D receptor (VDR) agonist elocalcitol
      can arrest prostate growth in BPH patients, but its mechanism of action in this
      pathology is still incompletely understood. METHODS: IL-8 levels were measured by
      real-time RT-PCR and ELISA. NF-kappaB translocation and COX-2 expression were
      evaluated by confocal microscopy. RhoA and Rho-kinase (ROCK) gene expression and
      functional activity were studied by real-time RT-PCR, immuno-kinase assays,
      Western blot analysis, confocal microscopy, and cell invasion. RESULTS:
      Stimulation of BPH cells with IL-8 activates the calcium-sensitizing RhoA/ROCK
      pathway, as demonstrated by the increased membrane translocation of RhoA and by
      phosphorylation of the ROCK substrate myosin phosphatase target subunit 1 (MYPT
      1). In agreement with these data, C3 exoenzyme, a selective RhoA inhibitor,
      inhibits IL-8-induced invasion of BPH cells. The VDR agonist elocalcitol
      significantly inhibits IL-8 production by BPH cells stimulated with inflammatory
      cytokines, and IL-8-induced proliferation of BPH cells. In addition, elocalcitol
      inhibits IL-8-induced membrane translocation of RhoA and MYPT-1 phosphorylation
      in BPH cells, and inhibits dose-dependently their IL-8-dependent invasion. The
      inhibition induced by elocalcitol of IL-8 production by BPH cells is accompanied
      by decreased COX-2 expression and PGE(2) production and by arrest of NF-kappaB
      p65 nuclear translocation, associated with inhibition of the RhoA/ROCK pathway.
      CONCLUSIONS: These data provide a mechanistic explanation for the anti
      proliferative and anti-inflammatory properties of elocalcitol in BPH cells.

PMID- 19107882
TI  - Free-standing 3D supramolecular hybrid particle structures.

PMID- 19107881
TI  - Prostate-specific membrane antigen and its truncated form PSM'.
AB  - BACKGROUND: Prostate specific membrane antigen (PSMA) is a type II transmembrane
      protein overexpressed in prostate cancer as well as in the neovasculature of
      several non-prostatic solid tumors. In addition to full-length PSMA, several
      splice variants exist in prostatic tissue. Notably, the N-terminally truncated
      PSMA variant, termed PSM', is prevalent in healthy prostate, and the ratio of
      PSMA/PSM' mRNA has been shown to correlate with cancer progression. The widely
      accepted hypothesis is that the PSM' protein is a translation product arising
      from the alternatively spliced PSM' mRNA. METHODS: Differential
      ultracentrifugation, cell surface biotinylation, Western blotting, and enzyme
      activity measurement were used to study the origin and localization of the
      PSMA/PSM' variants in prostatic (LNCaP; lymph-node carcinoma of the prostate) and
      non-prostatic (HEK293) cell lines. These experiments were further complemented by
      analysis of the N-glycosylation patterns of the PSMA/PSM' proteins and by site
      directed mutagenesis. RESULTS: We identified PSM' protein expression in both the
      LNCaP cell line and a non-cancerous HEK293 human cell line transfected with a
      plasmid encoding full-length PSMA. Differential centrifugation revealed that PSM'
      is localized predominantly to the cytosol of both these cell lines and is
      proteolytically active. Furthermore, the PSM' protein is N-glycosylated by a
      mixture of high-mannose and complex type oligosaccharides and therefore
      trafficked beyond the cis-Golgi compartment. CONCLUSIONS: Our data suggest that
      the PSM' protein is likely not generated by alternative splicing of the PSMA gene
      but by different mechanism, probably via an endoproteolytic cleavage of the full
      length PSMA.

PMID- 19107883
TI  - Dinitrogen reduction and C-H activation by the divalent organoneodymium complex
      [(C5H2tBu3)2Nd(mu-I)K([18]crown-6)].

PMID- 19107885
TI  - A nanoscale molecular switch triggered by thermal, light, and guest perturbation.
AB  - Bottoms up! A discrete metallo-supramolecular nanoball (see picture), synthesized
      by using "bottom-up" methodologies, uniquely undergoes a solvent-sensitive,
      physically addressable electronic spin switching. The switching occurs by
      thermal, light, or solvent perturbation, where importantly it can be switched
      "on" or "off" by green or red laser irradiation, respectively.

PMID- 19107884
TI  - Separation of nanoparticles in a density gradient: FeCo@C and gold nanocrystals.

PMID- 19107886
TI  - The effects of starting materials in the synthesis of (Ga(1-x)Znx)(N(1-x)O(x))
      solid solution on its photocatalytic activity for overall water splitting under
      visible light.
AB  - The influence of starting materials on the physicochemical and photocatalytic
      properties of (Ga(1-x)Zn(x))(N(1-x)O(x)) were investigated in an attempt to
      optimize the preparation conditions. The catalyst was successfully prepared by
      nitriding a starting mixture of ZnO and Ga2O3. A mixture of metallic zinc and
      GaN, however, did not afford the desired compound. The crystallinity, surface
      area, composition, and absorption characteristics of the resultant (Ga(1
      x)Zn(x))(N(1-x)O(x)) solid solution are found to be dependent on the morphology
      of ZnO but largely insensitive to the choice of Ga2O3 polymorph. The use of
      coarser-grained ZnO results in a coarser-grained catalyst with elevated zinc and
      oxygen content and reduced uniformity in composition and crystallinity. The
      results demonstrate the importance of selecting appropriate ZnO and Ga2O3
      starting materials for maximizing the photocatalytic activity of (Ga(1
      x)Zn(x))(N(1-x)O(x)) for overall water splitting under visible light.

PMID- 19107887
TI  - Metal-organic spheres as functional systems for guest encapsulation.
AB  - Music of the spheres: Infinite coordination polymerization of Zn(2+) ions and a
      multitopic ligand produces metal-organic micro- and nanospheres that can be used
      as functional matrices. The spheres can encapsulate combinations of active
      substances, such as organic dyes, magnetic nanoparticles, or luminescent quantum
      dots (see image), which results in spheres that are luminescent in the blue,
      green, and red regions of the spectrum.

PMID- 19107888
TI  - Ultrafine ZnO nanowire electronic device arrays fabricated by selective metal
      organic chemical vapor deposition.

PMID- 19107889
TI  - CMOS-Compatible nanowire sensor arrays for detection of cellular bioelectricity.

PMID- 19107890
TI  - Phase-inversion method for incorporation of metal nanoparticles into carbon
      nanotube/polymer composites.

PMID- 19107891
TI  - Systems chemistry: logic gates, arithmetic units, and network motifs in small
      networks.
AB  - A mixture of molecules can be regarded as a network if all the molecular
      components participate in some kind of interaction with other molecules--either
      physical or functional interactions. Template-assisted ligation reactions that
      direct replication processes can serve as the functional elements that connect
      two members of a chemical network. In such a process, the template does not
      necessarily catalyze its own formation, but rather the formation of another
      molecule, which in turn can operate as a template for reactions within the
      network medium. It was postulated that even networks made up of small numbers of
      molecules possess a wealth of molecular information sufficient to perform rather
      complex behavior. To probe this assumption, we have constructed virtual arrays
      consisting of three replicating molecules, in which dimer templates are capable
      of catalyzing reactants to form additional templates. By using realistic
      parameters from peptides or DNA replication experiments, we simulate the
      construction of various functional motifs within the networks. Specifically, we
      have designed and implemented each of the three-element Boolean logic gates, and
      show how these networks are assembled from four basic "building blocks". We also
      show how the catalytic pathways can be wired together to perform more complex
      arithmetic units and network motifs, such as the half adder and half subtractor
      computational modules, and the coherent feed-forward loop network motifs under
      different sets of parameters. As in previous studies of chemical networks, some
      of the systems described display behavior that would be difficult to predict
      without the numerical simulations. Furthermore, the simulations reveal trends and
      characteristics that should be useful as "recipes" for future design of
      experimental functional motifs and for potential integration into modular
      circuits and molecular computation devices.

PMID- 19107892
TI  - Galactose oxidase model: biomimetic enantiomer-differentiating oxidation of
      alcohols by a chiral copper complex.

PMID- 19107893
TI  - Antiferromagnetic ground state of a C(60)-covered Si(001) surface.
AB  - Modeling magnetism: The antiferromagnetic ground state of the C(60)/Si(001)
      c(4x4) surface is predicted by means of density functional theory calculations.
      Two adjacent dangling bonds (DBs) generated by the adsorption of C(60) are
      antiferromagnetically coupled with each other. This study demonstrates that
      magnetic Si surfaces can be prepared by engineering single Si DBs with unpaired
      electrons.

PMID- 19107895
TI  - Evaluation of frequencies of HPRT mutant lymphocytes in butadiene polymer workers
      in a Southeast Texas facility.
AB  - We examined the frequency of mutant lymphocytes (VFs) in workers (n = 30)
      occupationally exposed to the petrochemical, 1,3-butadiene (BD), using the
      autoradiographic HPRT mutant lymphocyte assay. Current exposures were determined
      with organic vapor monitors that had a 12-hr method detection limit (MDL) of 2.5
      parts per billion (ppb). HPRT VFs were analyzed with respect to current exposure
      estimates, age in years, and occupational longevity (OL; defined as years working
      in the BD industry at this facility). Current exposures were low (mean 93.5 ppb,
      median 2.5 ppb) with only one individual's estimate (1683.5 ppb) exceeding the
      Occupational Safety and Health Administration's permissible exposure limit of
      1,000 ppb. The majority (>50%) of current exposures were below the MDL. HPRT VFs
      were not significantly associated with current exposures (n = 29), and they were
      not significantly associated with age (n = 29). HPRT VFs were, however,
      significantly associated with OL (n = 29, R(2) = 0.107, P < 0.046). This result
      suggests that chronic and/or past, high-level exposures might leave a mutagenic
      signature that is revealed by the HPRT assay, possibly through the retention of
      mutant, long-term memory T-cells. While it is encouraging that current
      occupational exposures to BD in this facility do not appear to be increasing the
      frequency of mutant T-lymphocytes, evidence from workers with a lengthy history
      in the industry (>or=30 years in this case) indicates that these individuals
      likely require additional biomonitoring for possible mutagenic effects resulting
      from chronic, past exposures.

PMID- 19107896
TI  - Urinary levels of oxidative DNA and RNA damage among workers exposed to
      polycyclic aromatic hydrocarbons in silicon production: comparison with 1
      hydroxypyrene.
AB  - Polycyclic aromatic hydrocarbons (PAH) are ubiquitous occupational and
      environmental pollutants and the urinary excretion of 1-hydroxypyrene (1-OHP) is
      classically measured for the determination of PAH exposure internal dose. Some of
      PAH are tumorigenic due to their metabolites ability to generate DNA adducts and
      oxidative DNA damage through the production of reactive oxygen species during
      metabolism. 8-hydroxy-7,8-dihydro-2'-deoxyguanosine (8-OHdGuo) is one of the
      major oxidative DNA lesions and its use as a potential biomarker of genotoxic PAH
      occupational exposure should be evaluated. Indeed conflicting results are
      frequently reported in occupational studies in terms of correlation between 8
      OHdGuo urinary levels and PAH exposure. The aim of our study was therefore to
      determine the potential for PAH occupational exposure to increase urinary
      oxidative DNA damage. The population consisted of 68 male workers employed in
      silicon production. The urinary concentrations of 8-OHdGuo and its homologue in
      RNA, 8-hydroxy-7,8-dihydroguanosine (8-OHGuo) were determined using high
      performance liquid chromatography (HPLC) coupled to tandem mass spectrometry,
      whereas those of 1-OHP were measured using HPLC with fluorescence detection.
      Individual variation rates were calculated on a working day and a working week.
      The results indicated that, while 1-OHP levels strongly increased on a working
      day and even more on a working week, 8-OHdGuo and 8-OHGuo urinary levels did not
      show similar significant increases. Moreover, no correlation between 1-OHP and
      oxidative DNA and RNA lesions was found. Consequently, urinary 8-OHdGuo and 8
      OHGuo did not seem to be relevant biomarkers of genotoxic PAH exposure in the
      case of the silicon plant studied.

PMID- 19107897
TI  - Radiation-induced bystander effects in vivo are epigenetically regulated in a
      tissue-specific manner.
AB  - Exposure of animal body parts to ionizing radiation (IR) can lead to molecular
      changes in distant shielded "bystander" tissues and organs. Nevertheless, tissue
      specificity of bystander responses within the same organism has not been examined
      in detail. Studies on in vivo bystander effect conducted so far analyzed changes
      induced by single-dose exposure. The potential of fractionated irradiation to
      induce bystander effects in vivo has never been studied. We analyzed changes in
      global DNA methylation and microRNAome in skin and spleen of animals subjected to
      single-dose (acute or fractionated) whole-body or cranial exposure to 0.5 Gy of X
      rays. We found that IR-induced DNA methylation changes in bystander spleen and
      skin were distinct. Acute radiation exposure resulted in a significant loss of
      global DNA methylation in the exposed and bystander spleen 6 hr, 96 hr, and 14
      days after irradiation. Fractionated irradiation led to hypomethylation in
      bystander spleen 6 hr after whole-body exposure, and 6 hr, 96 hr, and 14 days
      after cranial irradiation. Contrarily, changes in the skin of the same animals
      were seen only 6 hr after acute whole-body and head exposure. DNA hypomethylation
      observed in spleen was paralleled by a reduction of methyl-binding protein MeCP2
      expression. Irradiation also induced tissue-specific microRNAome alterations in
      skin and spleen. For the first time, we have shown that IR-induced epigenetic
      bystander effects that occur in the same organism are triggered by both acute and
      fractionated exposure and are very distinct in different bystander organs. Future
      studies are clearly needed to address organismal and carcinogenic repercussions
      of those changes.

PMID- 19107899
TI  - Mycoplasma pulmonis and lymphoma.

PMID- 19107898
TI  - Investigation of relationships between transverse relaxation rate, diffusion
      coefficient, and labeled cell concentration in ischemic rat brain using MRI.
AB  - MRI has been used to evaluate labeled cell migration and distribution. However,
      quantitative determination of labeled cell concentration using MRI has not been
      systematically investigated. In the current study, we investigated the
      relationships between labeled cell concentration and MRI parameters of transverse
      relaxation rate, R(2), and apparent diffusion coefficient (ADC), in vitro in
      phantoms and in vivo in rats after stroke. Significant correlations were detected
      between iron concentration or labeled cell concentration and MRI measurements of
      R(2), ADC, and ADC x R(2) in vitro. In contrast, in vivo labeled cell
      concentration did not significantly correlate with R(2), ADC, and ADC x R(2). A
      major factor for the absence of a significant correlation between labeled cell
      concentration and MRI measurements in vivo may be attributed to background
      effects of ischemic tissue. By correcting the background effects caused by
      ischemic damage, DeltaR(2) (difference in R(2) values in the ischemic tissue with
      and without labeled cells) exhibited a significant correlation to labeled cell
      concentration. Our study suggests that MRI parameters have the potential to
      quantitatively determine labeled cell concentration in vivo.

PMID- 19107900
TI  - Comment on "Evaluation of evidence for infection as the mode of action for
      induction of rat lymphoma" by Caldwell et al. [2008].

PMID- 19107901
TI  - Searching for the origin of Gagauzes: inferences from Y-chromosome analysis.
AB  - The Gagauzes are a small Turkish-speaking ethnic group living mostly in southern
      Moldova and northeastern Bulgaria. The origin of the Gagauzes is obscure. They
      may be descendants of the Turkic nomadic tribes from the Eurasian steppes, as
      suggested by the "Steppe" hypothesis, or have a complex Anatolian-steppe origin,
      as postulated by the "Seljuk" or "Anatolian" hypothesis. To distinguish these
      hypotheses, a sample of 89 Y-chromosomes representing two Gagauz populations from
      the Republic of Moldova was analyzed for 28 binary and seven STR polymorphisms.
      In the gene pool of the Gagauzes a total of 15 Y-haplogroups were identified, the
      most common being I-P37 (20.2%), R-M17 (19.1%), G-M201 (13.5%), R-M269 (12.4%),
      and E-M78 (11.1%). The present Gagauz populations were compared with other
      Balkan, Anatolian, and Central Asian populations by means of genetic distances,
      nonmetric multidimentional scaling and analyses of molecular variance. The
      analyses showed that Gagauzes belong to the Balkan populations, suggesting that
      the Gagauz language represents a case of language replacement in southeastern
      Europe. Interestingly, the detailed study of microsatellite haplotypes revealed
      some sharing between the Gagauz and Turkish lineages, providing some support of
      the hypothesis of the "Seljuk origin" of the Gagauzes. The faster evolving
      microsatellite loci showed that the two Gagauz samples investigated do not
      represent a homogeneous group. This finding matches the cultural and linguistic
      heterogeneity of the Gagauzes well, suggesting a crucial role of social factors
      in shaping the Gagauz Y-chromosome pool and possibly also of effects of genetic
      drift.

PMID- 19107902
TI  - Physical growth in schoolchildren from Argentina: comparison with Argentinean and
      CDC/NCHs growth references.
AB  - The aim of this study was to assess the physical growth of schoolchildren from
      Argentina by comparison with the CDC/NCHS and Argentinean growth references
      (AGR), to contribute to the discussion about the use of local or international
      references for the assessment of growth in developing countries. Weight and
      height were measured in 3,411 schoolchildren aged 5-14 years. Data were log
      transformed and compared with both references by paired samples t-test (CI =
      0.95; alpha = 0.005). The boys' weights were greater than CDC/NCHS (up to 10, and
      at 14 years old) and the national reference at all ages (P < 0.005). The girls
      also were heavier than CDC/NCHS (at 7 and 12 years old, P < 0.005) and AGR,
      except at age 11 and 14 years. In boys, height was lower than CDC/NCHS at 9 and
      14 years of age, and higher than AGR at all ages (P < 0.005). The girls were also
      shorter than CDC/NCHS at 7, 13, and 14 years old (P < 0.005), and-except at age
      14-taller than AGR. The weight was higher than both of the references. Height
      showed a clear dissociation from the national reference and minor differences
      from CDC/NCHS. Nevertheless, around puberty, the children's height fell short of
      CDC/NCHS, especially the girls, whose values approached those of their
      Argentinean peers. This divergence could be associated with cohort effects or
      population variations in adolescent growth spurt. The use of a single growth
      reference for preadolescent may be appropriate. The height decrease in
      adolescents suggests the usefulness of local standards at this period.

PMID- 19107903
TI  - Maternal height and child mortality in 42 developing countries.
AB  - Previous research reports mixed results about the association between maternal
      height and child mortality. Some studies suggest that the negative association
      might be stronger in contexts with fewer resources. This hypothesis has yet not
      been tested in a cross-nationally comparative design. We use data on 307,223
      children born to 194,835 women in 444 districts of 42 developing countries to
      estimate the association between maternal height and child mortality and test
      whether this association is modified by indicators at the level of the household
      (like sex, age and twin status of the child and socio-economic characteristics of
      the mother and her partner), district (regional level of development, public
      health facilities and female occupational attainment) and country (GDP per
      capita). We find a robust negative effect of logged maternal height on child
      mortality. The effect of maternal health is strongest for women with least
      education and is more important in the first year after birth and for twin
      births. The indicators of development at the district and country level do not
      modify the effect of maternal height.

PMID- 19107904
TI  - Total estradiol levels in migrant and British-born British Pakistani women:
      investigating early life influences on ovarian function.
AB  - The purpose of this study was to test the hypothesis that women who grow up in
      energetically stressed environments have later menarche and lower total estradiol
      levels during their reproductive years than do women who grow up in less
      energetically stressed environments. We assessed total estradiol in a serum
      sample taken 9-11 days after the start of the menstrual cycle in 26 women who
      grew up in Pakistan and migrated to the UK as adults, in 28 British-born British
      Pakistani women, and in 25 British-born women of European origin. Women who grew
      up in Pakistan reported a later menarche than women who grew up in the UK.
      However, we found no significant differences between the groups in total
      estradiol level. Thus our findings do not support the hypothesis that estradiol
      levels are partially determined during early life. However, having considered our
      findings in relation to those of other studies, we conclude that new
      methodological approaches are needed to provide a more definitive test of the
      hypothesis.

PMID- 19107905
TI  - Adiponectin and type 2 diabetes in Samoan adults.
AB  - OBJECTIVE: Previous studies have established an association between adiponectin
      and type 2 diabetes. It is unclear whether adiponectin will be useful among
      Samoan Islanders, characterized by markedly elevated levels of obesity, in
      differentiating those at risk of developing type 2 diabetes. METHODS: Cross
      sectional, genetic epidemiology study of obesity in American Samoa and Samoa 2002
      2003 (n = 1,599). Logistic regression provided adjusted odds ratios and 95%
      confidence intervals for the association between adiponectin, diabetes, and
      prediabetes (impaired fasting glucose). RESULTS: There is a significant
      decreasing trend in the odds of diabetes and prediabetes across increasing
      quintiles of adiponectin with an OR of 2.8 (95% CI: 1.6, 5.0) and 2.9 (95% CI:
      1.5, 5.7), respectively, in the lowest relative to the highest quintile of
      adiponectin (P-for-trend = 0.004 and 0.001). CONCLUSIONS: Adiponectin is an
      important correlate, independent of other risk factors, of the pathogenesis of
      type 2 diabetes among Samoan islanders and may help distinguish those at higher
      risk of developing this disease.

PMID- 19107906
TI  - The design and use of an agent-based model to simulate the 1918 influenza
      epidemic at Norway House, Manitoba.
AB  - Agent-based modeling provides a new approach to the study of virgin soil
      epidemics like the 1918 flu. In this bottom-up simulation approach, a landscape
      can be created and populated with a heterogeneous group of agents who move and
      interact in ways that more closely resemble human behavior than is usually seen
      in other modeling techniques. In this project, an agent-based model was
      constructed to simulate the spread of the 1918 influenza pandemic through the
      Norway House community in Manitoba, Canada. Archival, ethnographic,
      epidemiological, and biological information were used to aid in designing the
      structure of the model and to estimate values for model parameters. During the
      epidemic, Norway House was a Hudson's Bay Company post and a Swampy Cree-Metis
      settlement with an economy based on hunting, fishing, and the fur trade. The
      community followed a traditional, seasonal travel pattern of summer aggregation
      and winter dispersal. The model was used to examine how seasonal community
      structures and associated population movement patterns may have influenced
      disease transmission and epidemic spread. Simulations of the model clearly
      demonstrate that human behavior can significantly influence epidemic outcomes.

PMID- 19107907
TI  - Cigarette smoke extract induces expression of cell adhesion molecules in HUVEC
      via actin filament reorganization.
AB  - Epidemiologic studies have shown a strong association between cigarette smoking
      and cardiovascular diseases. Various oxidative species and free radicals are
      produced during cigarette smoking and these lead to endothelial dysfunction and
      inflammation. Expression of adhesion molecules, such as intercellular adhesion
      molecule-1 (ICAM-1), E-selectin, and vascular cell adhesion molecule-1, and
      adhesion of leukocytes are present in atherosclerosis. We showed previously that
      a nonfractionated cigarette smoke extract (CSE) induces surface expression of
      ICAM-1 and E-selectin in human umbilical vein endothelial cells (HUVEC). We then
      investigated the role of the MAPKs (ERK1/2, JNK, and p38) and AP-1 and the role
      of actin cytoskeleton reorganization in the CSE-induced expression of ICAM-1 and
      E-selectin. Western blot analysis showed that CSE treatment rapidly and
      significantly caused phosphorylation of JNK and ERK1/2 but not of p38.
      Cytochalasin D (an actin filament disruptor) partially inhibited CSE-induced ICAM
      1 and E-selectin surface expression. However, inhibitors of ERK1/2 (PD98059) and
      JNK (SP600125) did not attenuate the CSE-induced ICAM-1 and E-selectin surface
      expression. The results of electrophoretic mobility shift assay showed that CSE
      enhanced AP-1 binding activity. Therefore, CSE activated AP-1 and upregulated
      ICAM-1 and E-selectin surface expression in HUVEC seem to be via an MAPK
      independent pathway. Moreover, the dynamic reorganization of the actin
      cytoskeleton seems to be required for the CSE-induced surface expression of ICAM
      1 and E-selectin.

PMID- 19107908
TI  - A novel germline mutation in Big Blue mice.
AB  - The Big Blue lacI mutation detection assay is well validated and has permitted
      detailed analysis of spontaneous mutations in individual tissues over the
      lifespan of the mouse. In a recent assay of spontaneous mutations, a novel lacI
      mutation (C354T) recurred in six of seven mutants with a second mutation. The
      frequency of spontaneous doublets (mutants with two nontandem mutations) was
      elevated 2.7-fold over that previously reported (Hill KA et al., [2004b]: Mutat
      Res 554:223-240) for normal tissues (6.3 x 10(-7) herein vs. 2.36 x 10(-7)). The
      average spacing between mutations in the doublets (237 bp) was greater than
      previously reported for spontaneous doublets. The frequency of C354T as a
      "hitchhiker" mutation in doublets was consistent with a germline mutation in one
      of 38 mutation targets in the Big Blue mouse genome. C354T is a missense mutation
      at a CpG dinucleotide producing a conservative amino acid change (Ala109Val) and
      a very light blue mutant phenotype. Mutant phenotypes of doublets with C354T were
      typical of the second mutation. C354T was observed in mutants from five tissues
      of five Big Blue mice. A bidirectional-PCR amplification of specific alleles (Bi
      PASA) assay detected C354T in genomic DNA from multiple tissues of five Big Blue
      mice. These observations are consistent with a novel lacI C354T germline mutation
      in Big Blue mice that introduces a significant artifact in the analysis of
      spontaneous mutations. This finding reiterates the importance of identifying all
      mutations and examining new mutations in the context of our increasingly detailed
      knowledge of features of spontaneous murine mutations.

PMID- 19107909
TI  - Investigation of the genotoxic effect of pesticides on greenhouse workers'
      lymphocytes.
AB  - In the present study, the genotoxic effects of commonly applied pesticides were
      evaluated using the alkaline comet assay (pH > 13). The amount of DNA damage (%
      DNA in tail) in peripheral lymphocytes of 49 male agricultural workers from
      Southern Poland were measured and compared to 50 men from the same area who had
      no previous occupational exposure to pesticides. No statistically significant
      differences in basal DNA damage were found between the study groups. In addition,
      exposure of peripheral blood lymphocytes to hydrogen peroxide (100 and 150
      microM) or gamma-irradiation (2.5 or 4.2 Gy) led to a similar degree of
      additional DNA damage and subsequent repair (for 2 hr) for all studied
      populations. In conclusion, our results indicate that the greenhouse workers who
      participated in this study had no detectable increased DNA damage or alteration
      in their cellular response to DNA damage in comparison to our control population.

PMID- 19107910
TI  - NAT2 fast acetylator genotype and MGMT promoter methylation may contribute to
      gender difference in K-RAS mutation occurrence in Taiwanese colorectal cancer.
AB  - A recent study conducted by our group showed that the NAT2 fast acetylator
      genotype is associated with an increasing risk for the development of colorectal
      cancer (CRC), especially for females. We therefore examined whether a higher risk
      of CRC in females with the NAT2 fast acetylator genotype was associated with the
      occurrence of K-RAS mutation, and to further verify whether MGMT promoter
      methylation was linked to the occurrence of K-RAS mutation in patients with the
      NAT2 fast acetylator genotype. Herein, 151 CRC cases were examined for NAT2
      genetic polymorphisms and MGMT promoter methylation by PCR-RFLP and methylation
      specific PCR (MSP). The results of this study show that the NAT2 fast acetylator
      genotype is associated with the occurrence of K-RAS mutation in female cases (OR
      = 4.820, 95% CI = 1.113-20.873), but not associated with MGMT promoter
      methylation. Surprisingly, MGMT promoter methylation significantly deepens the
      impact of NAT2 fast acetylation on K-RAS mutation in the female cases (OR =
      5.129, 95% CI = 1.092-24.105). In conclusion, Taiwanese women with the NAT2 fast
      acetylator genotype may exhibit a higher risk of CRC with increased occurrence of
      K-RAS mutation. Detection of NAT2 genotypes and MGMT promoter methylation may be
      useful in the risk assessment for CRC in Taiwanese women.

PMID- 19107911
TI  - Sheldon Wolff 1928-2008.

PMID- 19107913
TI  - Helical polyacetylene--origins and synthesis.
AB  - We present the origins and synthesis of helical polyacetylene (H-PA) by focusing
      on its peculiar spiral morphology. Interfacial polymerization of acetylene was
      carried out in an asymmetric reaction field consisting of chiral nematic liquid
      crystal (N*-LC) and Ziegler-Natta catalyst. As the N*-LC is composed of nematic
      liquid crystal and a chiral compound such as a binaphthyl derivative with either
      the R- or S-configuration, the screw directions of the polyacetylene chain and
      fibril bundle--and even the spiral morphology--are rigorously controlled by the
      chirality of the selected compound. Interestingly, the screw directions of the
      fibril and the bundle in H-PA were found to be opposite to that of N*-LC. It is
      worthwhile to emphasize that the hierarchical spiral morphology involving the
      primary to higher order structure is generated in a synthetic polymer such as
      polyacetylene by using N*-LC as an asymmetric polymerization solvent.

PMID- 19107914
TI  - Retrospective correction for induced magnetic field inhomogeneity in measurements
      of large-vessel hemoglobin oxygen saturation by MR susceptometry.
AB  - MR susceptometry-based blood oximetry relies on phase mapping to measure the
      difference in magnetic susceptibility between intravascular blood and surrounding
      tissue. The main source of error in MR susceptometry is the static field
      inhomogeneity caused by an interface between air and tissue or between adjacent
      tissue types. High-pass filtering has previously been used in conjunction with
      shimming to reduce the effect of low spatial-frequency modulations of the phase
      caused by large-scale induced magnetic fields. We demonstrate that high-pass
      filtering is not optimum for MR susceptometry because the results are sensitive
      to filter size. We propose an alternative method that acquires data without
      scanner-implemented default shimming, and fits, after appropriate weighting and
      masking, the static field inhomogeneity to a second-order polynomial. Compared to
      shimming the retrospective correction technique improved agreement between
      hemoglobin saturations measured in different segments of a vessel (femoral versus
      popliteal artery and vein) from three standard errors to less than one.

PMID- 19107916
TI  - Post-activation treatment with demecolcine improves development of somatic cell
      nuclear transfer embryos in pigs by modifying the remodeling of donor nuclei.
AB  - The objective of this study was to examine the effect of cytochalasin B (CB)
      and/or demecolcine (Dc) on the remodeling of donor nuclei, nuclear ploidy, and
      development of somatic cell nuclear transfer (SCNT) and parthenogenetic (PA) pig
      embryos. SCNT and PA oocytes were either untreated (control), or treated with CB,
      Dc, or both CB and Dc after electric activation, and then cultured or transferred
      to surrogates. In SCNT, blastocyst formation was higher after treatment with CB
      and/or Dc (26-28%) than in the controls (16%). The number of oocytes that formed
      a single pronucleus (PN) was higher after treatment with Dc (86%) and CB + Dc
      (86%) than under control conditions (44%) or after treatment with CB (63%). In
      PA, blastocyst formation was higher after CB treatment (47%) than under control
      conditions (28%), while the formation of a single PN was higher after treatment
      with Dc (88%) and CB + Dc (84%) compared to controls (34%). The rate of formation
      of diploid embryos was higher after treatment with Dc and CB + Dc than under
      control conditions. Dc treatment resulted in a farrowing rate of 50% with 1.1%
      production efficiency, while controls showed a farrowing rate of 37.5% and a
      production efficiency of 0.7%. The results of our study demonstrate that post
      activation treatment with Dc improves preimplantation development and supports
      normal in vivo development of SCNT pig embryos, probably because Dc induces
      formation of a single PN and this leads to normal nuclear ploidy.

PMID- 19107917
TI  - Nineteenth-century population structure of Ireland and of the Irish in England
      and Wales: an analysis by isonymy.
AB  - This article uses isonymy to test predictions about the genetic structure of
      Irish populations made on the basis of geography and population history, and
      compares the mid-nineteenth century population of Ireland with the late
      nineteenth century Irish-born population resident in England and Wales. Surname
      data were derived from (1) the householders named in the index to Griffith's
      valuation of Ireland, a survey undertaken between 1846 and 1864, and (2) of Irish
      born residents named in 1881 census of England and Wales. Visual representation
      of the Griffith's valuation isonymy matrix by multidimensional scaling (MDS)
      gives a result very close to the geographical distribution of Irish counties, and
      Mantel matrix correlation shows random isonymy between counties to be negatively
      associated with geographical distance, generally decaying according to a pattern
      of isolation-by-distance, with exceptions that can be explained in terms of Irish
      population history. Some 141,360 Irish-born residents in England and Wales at the
      1881 census were assigned to an Irish county of origin, and random isonymy by
      county of birth for this group also shows a close correspondence to Irish
      geography. The Mantel matrix correlation between the Irish in Ireland and the
      Irish in England is 0.855, R(2) = 0.7306, indicating that the emigrant Irish in
      England were representative of the populations of the Irish counties from which
      they were derived. This result, together with the strong geographical patterning
      of surnames in Ireland, suggests that isonymy can be used to investigate the
      population structure and origin of Irish emigrant groups in Britain and
      potentially throughout the Irish diaspora.

PMID- 19107918
TI  - Response to: Huber S, Fieder M. 2008. Strong association between birth month and
      reproductive performance of Vietnamese women. Am J Hum Biol DOI:
      10.1002/ajhb.20799.

PMID- 19107920
TI  - Tracing the distribution and evolution of lactase persistence in Southern Europe
      through the study of the T(-13910) variant.
AB  - We investigated the occurrence and intra-allelic variability of the T(-13910)
      variant located upstream of the lactase gene in 965 individuals from 20 different
      locations of Italy and Greece. The T(-13910) frequency ranges from 0.072
      (Sardinia) to 0.237 (North-East Italy), with a statistically significant
      difference between North-East Italians and other Italian populations. The
      comparison of the lactose tolerance predicted by T(-13910) and that assessed by
      other studies using physiological tests shows a one-way statistically significant
      discrepancy that could be due to sampling differences. However, the possible role
      of other genetic factors underlying lactase persistence is worth exploring. The
      time of the most recent common ancestor and departures from neutrality of the T(
      13910) allele were assessed using three microsatellite loci. Time estimates were
      found to be congruent with the appearance of dairy farming in Southern Europe and
      the occurrence of a single introgression event. Robust signals of selection can
      be observed in North-East Italy only. We discuss the possible role of cultural
      traits and genetic history in determining these observed micro-evolutionary
      patterns.

PMID- 19107921
TI  - Life course weight gain and C-reactive protein levels in young adults: findings
      from a Brazilian birth cohort.
AB  - Rapid weight gain in childhood is associated with increased risk of chronic
      diseases in adults. C-reactive protein (CRP) is a mediator of atherosclerosis and
      chronically elevated levels predict cardiovascular outcomes. The effects of life
      course weight gain on CRP levels are not clear. The 1982 Pelotas (Brazil) birth
      cohort study (n = 5,914) has prospectively collected weight and health data at
      several follow-ups since birth. The most recent was in 2004-05, when 77.4% of the
      cohort was traced and CRP levels were measured in 89% of those interviewed (n =
      3827). Geometric mean (SE) C-reactive protein levels were 0.89 mg/l (0.03) and
      1.66 mg/l (0.04) in men and women, respectively. In analyses adjusted for
      confounding variables, weight gain in infancy showed a weak negative association
      among males, but from the second year onwards, weight gain was positively
      associated with CRP levels. In females, weight gain was associated with higher
      CRP at every period tested. The strongest associations were observed in the most
      recent (18-23 years) period; CRP ratios (95% CI) per z score increase in weight
      gain were 1.78 (1.57-2.00) and 1.52 (1.30-1.78) for men and women, respectively.
      Males who were stunted at 2 years and centrally obese at 23 years had the highest
      CRP levels (P = 0.002 for interaction). In summary, rapid weight gain throughout
      life predicted higher CRP levels. Public health efforts need to tackle chronic
      under-nutrition in infancy, together with rapid weight gain in later childhood
      and adolescence, especially in countries undergoing the nutritional transition.

PMID- 19107922
TI  - Relationship of polymorphisms located in tumor necrosis factor region and HLA
      loci among Croatians.
AB  - Polymorphism of TNFa, TNFb, and TNFd microsatellites, linkage disequilibrium (LD)
      within TNF region as well as relationship of TNF microsatellites with alleles at
      HLA-A, -B, and -DRB1 loci was investigated on a sample of 160 Croatians,
      previously typed for HLA-A, -B, and -DRB1 loci. Analysis of the relationship of
      TNF alleles and HLA specificities revealed that very strong associations exist
      between TNFa2, TNFb3, and TNFd2 alleles and HLA-A*01, -B*08, and -DRB1*03
      specificities, therefore placing them in the 8.1 ancestral haplotype. Similar
      findings were observed for TNFa11, TNFb4, and TNFd4 alleles and HLA
      specificities, which are a part of the 7.1 ancestral haplotype. Finally, multiple
      associations with significant P-values were also observed between TNFa10, TNFb4,
      and TNFd4 microsatellite alleles and HLA-A*02, -B*18, -DRB1*11 specificities
      which form the 18.3 ancestral hapolotype.

PMID- 19107924
TI  - Digit ratio (2D:4D) and sprinting speed in boys.
AB  - Digit ratio (2D:4D), a putative correlate of prenatal testosterone, has been
      found to relate to performance in sport and athletics such that low 2D:4D (high
      prenatal testosterone) correlates with high performance. Speed in endurance races
      is strongly related to 2D:4D, and may be one factor that underlies the link
      between sport and 2D:4D, but nothing is known of the relationship between 2D:4D
      and sprinting speed. Here we show that running times over 50 m were positively
      correlated with 2D:4D in a sample of 241 boys (i.e. runners with low 2D:4D ran
      faster than runners with high 2D:4D). The relationship was also found for 50 m
      split times (at 20, 30, and 40 m) and was independent of age, BMI, and an index
      of maturity. However, associations between 2D:4D and sprinting speed were much
      weaker than those reported for endurance running. This suggests that 2D:4D is a
      relatively weak predictor of strength and a stronger predictor of efficiency in
      aerobic exercise. We discuss the effect sizes for relationships between 2D:4D and
      sport and target traits in general, and identify areas of strength and weakness
      in digit ratio research.

PMID- 19107923
TI  - Height and relative leg length as indicators of the quality of the environment
      among Mozambican juveniles and adolescents.
AB  - The growth status of Mozambique adolescents was assessed to test the hypothesis
      that relative leg length is a more sensitive indicator of the quality of the
      environment than the total height. The sample comprised 690 boys and 727 girls,
      aged between 9 and 17 years, from Maputo. It is divided between those living in
      the Centre of Maputo and those living in the slums on the periphery of the city.
      Height, weight, and sitting height were measured and the sitting height ratio was
      calculated. The hypothesis that relative leg length is more sensitive than total
      stature as an indicator of environmental quality is not uniformly confirmed.
      Overall, mean stature is greater for the centre group than the slum group, but
      relative leg length as measured by the sitting height ratio does not differ.
      Compared with African-American references (NHANES II), all centre girls, 9- to 14
      year-old slum girls, all slum boys, and the oldest centre boys show relatively
      shorter legs. These findings show that within the Mozambique sample, relative leg
      length is not sensitive enough to distinguish the quality of the living
      environment. Mozambique was a colony of Portugal until 1975. Civil unrest and
      warfare characterized the late Colonial period and the postindependence period
      until a peace settlement was concluded in 1992. It is possible that all
      socioeconomic status groups within the country suffered sufficiently to reduce
      relative leg length compared with the better-off African-American reference
      sample. Possible genetic influences on relative leg length are also discussed.

PMID- 19107925
TI  - Identification of novel peptide ligands for the cancer-specific receptor mutation
      EFGRvIII using a mixture-based synthetic combinatorial library.
AB  - We report here, the design and synthesis of a positional scanning synthetic
      combinatorial library for the identification of novel peptide ligands targeted
      against the cancer-specific epidermal growth factor tyrosine kinase receptor
      mutation variant III (EGFRvIII). This receptor is expressed in several kinds of
      cancer, in particular, ovarian, glioblastomas, and breast cancer, but not in
      normal tissue. The library consisted of six individual positional sublibraries in
      the format, H-O(1-6)XXXXX-NH(2), O being one of the 19 proteinogenic amino acids
      (cysteine omitted) and X an equimolar mixture of these. The library consisted of
      114 mixtures in total. Using a biotin-streptavidin assay, the binding of each
      sublibrary to NR6M, NR6W-A, and NR6 cells was tested. These cells express
      EGFRvIII, EGFR, and neither of the receptors, respectively. The result from each
      sublibrary was examined to identify the most active amino acid residue at each
      position. On the basis of this knowledge, eight peptides were synthesized and
      tested for binding to EGFRvIII. We identified one peptide, H-FALGEA-NH(2), that
      showed more selective binding to the mutated receptor than the EGFRvIII specific
      peptide PEPHC1. This study demonstrates the value of using mixture-based
      combinatorial positional scanning libraries for the identification of novel
      peptide ligands targeted against the cancer-specific EGFRvIII. Our best candidate
      H-FALGEA-NH(2) will be radioactively labeled and evaluated as an imaging agent
      for positron emission tomography investigation for diagnosis, staging, and
      monitoring of therapy of various types of cancer.

PMID- 19107926
TI  - NMR structure of rALF-Pm3, an anti-lipopolysaccharide factor from shrimp: model
      of the possible lipid A-binding site.
AB  - The anti-lipopolysaccharide factor ALF-Pm3 is a 98-residue protein identified in
      hemocytes from the black tiger shrimp Penaeus monodon. It was expressed in Pichia
      pastoris from the constitutive glyceraldehyde-3-phosphate dehydrogenase promoter
      as a folded and (15)N uniformly labeled rALF-Pm3 protein. Its 3D structure was
      established by NMR and consists of three alpha-helices packed against a four
      stranded beta-sheet. The C(34)-C(55) disulfide bond was shown to be essential for
      the structure stability. By using surface plasmon resonance, we demonstrated that
      rALF-Pm3 binds to LPS, lipid A and to OM-174, a soluble analogue of lipid A.
      Biophysical studies of rALF-Pm3/LPS and rALF-Pm3/OM-174 complexes indicated
      rather high molecular sized aggregates, which prevented us to experimentally
      determine by NMR the binding mode of these lipids to rALF-Pm3. However, on the
      basis of striking structural similarities to the FhuA/LPS complex, we designed an
      original model of the possible lipid A-binding site of ALF-Pm3. Such a binding
      site, located on the ALF-Pm3 beta-sheet and involving seven charged residues, is
      well conserved in ALF-L from Limulus polyphemus and in ALF-T from Tachypleus
      tridentatus. In addition, our model is in agreement with experiments showing that
      beta-hairpin synthetic peptides corresponding to ALF-L beta-sheet bind to LPS.
      Delineating lipid A-binding site of ALFs will help go further in the de novo
      design of new antibacterial or LPS-neutralizing drugs.

PMID- 19107929
TI  - Fruit and vegetable consumption and pancreatic cancer risk in the European
      Prospective Investigation into Cancer and Nutrition.
AB  - Many case-control studies have suggested that higher consumption of fruit and
      vegetables is associated with a lower risk of pancreatic cancer, whereas cohort
      studies do not support such an association. We examined the associations of the
      consumption of fruits and vegetables and their main subgroups with pancreatic
      cancer risk within the European Prospective Investigation into Cancer and
      Nutrition (EPIC). EPIC is comprised of over 520,000 subjects recruited from 10
      European countries. The present study included 555 exocrine pancreatic cancer
      cases after an average follow-up of 8.9 years. Estimates of risk were obtained by
      Cox proportional hazard models, stratified by age at recruitment, gender, and
      study center, and adjusted for total energy intake, weight, height, history of
      diabetes mellitus, and smoking status. Total consumption of fruit and vegetables,
      combined or separately, as well as subgroups of vegetables and fruits were
      unrelated to risk of pancreatic cancer. Hazard ratios (95% CI) for the highest
      versus the lowest quartile were 0.92 (0.68-1.25) for total fruit and vegetables
      combined, 0.99 (0.73-1.33) for total vegetables, and 1.02 (0.77-1.36) for total
      fruits. Stratification by gender or smoking status, restriction to
      microscopically verified cases, and exclusion of the first 2 years of follow-up
      did not materially change the results. These results from a large European
      prospective cohort suggest that higher consumption of fruit and vegetables is not
      associated with decreased risk of pancreatic cancer.

PMID- 19107930
TI  - Gold(III) porphyrin complex is more potent than cisplatin in inhibiting growth of
      nasopharyngeal carcinoma in vitro and in vivo.
AB  - Nasopharyngeal carcinoma (NPC) is a common neoplasm in Southeastern Asia, and
      cisplatin-containing regimens for combinational chemotherapy are widely used for
      treating locally recurrent or metastatic diseases. However, resistance to
      cisplatin is not infrequently seen and its associated side effects may be life
      threatening. In this report, another metallo-pharmaceutical agent gold(III)
      porphyrin complex [Au(TPP)]Cl was investigated in comparison to cisplatin for its
      in vitro and in vivo anticancer effects. Through induction of the intrinsic
      apoptosis pathway, [Au(TPP)]Cl exhibited 100-fold higher potency than cisplatin
      in killing NPC cells, including cisplatin-sensitive and cisplatin-resistant
      variants, and also an variant harboring the Epstein-Barr virus. In addition, a
      safety concentration window was demonstrated, allowing [Au(TPP)]Cl to kill tumors
      with minimal cytotoxicity to noncancerous cells. More importantly, weekly
      intraperitoneal injection of 3 mg/kg [Au(TPP)]Cl was more effective than the same
      dose of cisplatin in inducing tumor apoptosis in vivo and remarkably inhibited
      tumor growth in animals without any noticeable side effect. [Au(TPP)]Cl therefore
      is a promising chemotherapeutic agent that deserves further development as a
      novel drug for the treatment of advanced NPC, in particular, for cases with
      cisplatin-resistance.

PMID- 19107931
TI  - Chemokine receptor CXCR4 expression is correlated with VEGF expression and poor
      survival in soft-tissue sarcoma.
AB  - The expression of chemokine receptor CXCR4 has been associated with poor
      prognosis and VEGF expression in several kinds of human malignancy. We measured
      CXCR4 expression levels in soft-tissue sarcoma and compared them with VEGF
      expression or microvessel density (MVD). We used real-time quantitative PCR to
      examine the CXCR4 and VEGF expression levels in a total 176 tumors, including 24
      intermediate tumors, 24 malignant round-cell tumors (MRCTs) and 128 malignant non
      round-cell tumors (MNRCTs). We also assessed their immunohistochemical expression
      of CXCR4 and VEGF, MVD and proliferative activities, as measured by the MIB-1
      labeling index (LI). Furthermore, we evaluated their significance with respect to
      patient survival rates in MNRCTs, using the Cox regression model. Within the
      different types of tumor tissue, the expression levels of CXCR4 (p < 0.0001) and
      VEGF (p < 0.0001) in MNRCTs were significantly higher than those in intermediate
      tumors or MRCTs. Immunohistochemical expression levels of CXCR4 and VEGF were
      significantly correlated with their mRNA expression levels (p < 0.0001).
      Significant positive correlation was found between CXCR4 and VEGF expression in
      112 primary MNRCTs (r = 0.434, p < 0.0001). Moreover, both univariate (p <
      0.0001) and Cox multivariate analysis (p = 0.0001) revealed that overexpression
      of CXCR4 was an independent adverse prognostic factor, in addition to high stage
      according to the American Joint Committee on Cancer and a high MIB-1-LI.
      Determination of the CXCR4 expression level as a novel marker can provide useful
      prognostic information for patients and it could be a candidate for molecular
      targeting therapy in MNRCTs of soft-tissue sarcomas.

PMID- 19107932
TI  - Higher regular coffee and tea consumption is associated with reduced endometrial
      cancer risk.
AB  - Several studies have investigated the associations between diet and endometrial
      cancer, but few have focused specifically on coffee and tea. In a hospital-based
      case-control study, we examined the associations between endometrial cancer risk
      and usual consumption of coffee, decaffeinated coffee, and black tea among 541
      women with endometrial cancer and 541 women with an intact uterus but without a
      cancer diagnosis seen at Roswell Park Cancer Institute (Buffalo, New York)
      between 1982 and 1998. Daily frequency of consumption of coffee, decaffeinated
      coffee, and black tea in the few years prior to diagnosis in cases and
      questionnaire completion in controls was assessed with a self-administered
      epidemiologic questionnaire and categorized as none, 0.5 cups/d, 1-2 cups/d and
      >2 cups/d. Odds ratios (OR) and 95% confidence intervals (CI) for each category
      referent to nondrinkers were estimated with unconditional logistic regression
      adjusting for age, endometrial cancer risk factors and each beverage mutually
      adjusted for other beverages. Compared to nondrinkers, we observed a
      nonsignificant negative association with endometrial cancer risk among women who
      reported >2 cups/d regular coffee (OR 0.71, 95% CI 0.49-1.03), a significant
      inverse association with >2 cups/d black tea (OR 0.56, 95% CI 0.35-0.90) and a
      significant inverse association with >4 cups/d combined coffee and tea
      consumption (OR 0.47, 95% CI 0.28-0.80). These findings suggest coffee and tea
      may be important in reducing endometrial cancer risk.

PMID- 19107933
TI  - Comment on interaction of hormone replacement therapy with calcium and vitamin D
      supplementation on colorectal cancer risk.

PMID- 19107935
TI  - HAI-2 is epigenetically downregulated in human hepatocellular carcinoma, and its
      Kunitz domain type 1 is critical for anti-invasive functions.
AB  - Pharmacological demethylation-based gene expression profile analysis is a useful
      tool to identify epigenetically silenced tumour suppressor genes. HGF activator
      inhibitor 2 (HAI-2), a serine protease inhibitor, has been identified as one of
      the candidate tumour suppressor genes in human hepatocellular carcinoma (HCC)
      with this technique. In this study, we aimed to characterise the epigenetic
      status and tumour suppressive function of HAI-2 in HCC. We validated that HAI-2
      expression was either absent or low in most of the HCC cell lines tested, and 5
      Aza-2'-deoxycytidine treatment significantly restored its expression in 9 (75%)
      of these 12 cell lines. HAI-2 was found to be frequently underexpressed in human
      HCCs (p < 0.001). With bisulphite DNA sequencing and methylation-specific PCR, we
      found that the promoter of the HAI-2 gene was frequently hypermethylated in both
      HCC cell lines and human HCCs. Ectopic expression of HAI-2 significantly
      inhibited cell migration and invasiveness of HCC cells in vitro and suppressed
      tumourigenicity in vivo. In addition, we also provided the first evidence that
      HAI-2 mediated its tumour suppressor function via the Kunitz domain 1 (KD-1), as
      KD-1 but not KD-2 inactivating mutant abolished its anti-tumour invasiveness in
      vitro. Our findings suggest that HAI-2 is a candidate tumour suppressor gene that
      is frequently hypermethylated and underexpressed in human HCCs, and the KD-1
      domain of HAI-2 is the key region responsible for its anti-invasive function.

PMID- 19107936
TI  - Polymorphisms in ABCG2, ABCC3 and CNT1 genes and their possible impact on
      chemotherapy outcome of lung cancer patients.
AB  - The prognosis of lung cancer patients treated with chemotherapy is poor,
      motivating the search for predictive factors. Single nucleotide polymorphisms
      (SNPs) in membrane transporter genes could influence the pharmacokinetics of
      cytostatic drugs and therefore affect treatment outcome. We examined 6 SNPs with
      known or suspected phenotypic effect: ABCG2 G34A, C421A; ABCC3 C-211T, G3890A,
      C3942T and CNT1 G565A. For 349 Caucasian patients with primary lung cancer [161
      small cell lung cancer (SCLC), 187 nonsmall cell lung cancer (NSCLC) and 1 mixed]
      receiving first-line chemotherapy 3 different endpoints were analyzed: response
      after the 2nd cycle (R), progression-free survival (PFS) and overall survival
      (OS). The prognostic value of the SNPs was analyzed using multivariable logistic
      regression, calculating odds ratios (ORs) when comparing genotype frequencies in
      responders and nonresponders after the 2nd cycle. Hazard ratios (HRs) for PFS and
      for OS were calculated using Cox regression methods. In all lung cancer patients,
      none of the investigated polymorphisms modified response statistically
      significant. The only significant result in the histological subpopulations was
      in SCLC patients carrying the ABCC3 -211T allele who showed significantly
      worsened PFS (HR: 1.79; 95% confidence interval (CI) 1.13-2.82). In an
      exploratory subgroup analysis significantly worse OS was seen for carriers of the
      ABCG2 421A-allele treated with platinum-based drugs (HR: 1.60; 95% CI 1.04-2.47;
      n = 256). In conclusion, this study prioritizes ABCC3 C-211T and ABCG2 C421A as
      candidate transporter SNPs to be further investigated as possible predictors of
      the clinical outcome of chemotherapy in lung cancer patients.

PMID- 19107937
TI  - Increased risk of esophageal squamous cell carcinoma in patients with gastric
      atrophy: independent of the severity of atrophic changes.
AB  - An association between gastric atrophy and esophageal squamous cell carcinomas
      (ESCC) has been described. However, the mechanism of this association is unknown.
      In this study, we aimed to examine this relationship in a cohort of patients with
      varying grades of gastric atrophy to increase the understanding about the
      causality of the association. Patients diagnosed with gastric atrophy between
      1991 and 2005 were identified in the Dutch nationwide histopathology registry
      (PALGA). The incidence of ESCC and, presumably unrelated, small cell lung
      carcinomas (SCLC) observed in these patients was compared with that in the
      general Dutch population. Relative risks (RRs) and 95% confidence intervals were
      calculated by a Poisson model. At baseline histological examination, 97,728
      patients were diagnosed with gastric atrophy, of whom 23,278 with atrophic
      gastritis, 65,934 with intestinal metaplasia and 8,516 with dysplasia. During
      follow-up, 126 patients were diagnosed with ESCC and 263 with SCLC (overall rates
      0.19, respectively 0.39/1,000 person-years at risk). Compared with the general
      Dutch population, patients with gastric atrophy ran a RR of developing ESCC of
      2.2 [95% CI 1.8-2.6] and of SCLC of 1.8 [95% CI 1.6-2.1]. The risk of ESCC did
      not increase with increasing severity of gastric atrophy (p = 0.90). In
      conclusion, this study found an association between gastric atrophy and both ESCC
      and SCLC, but the risk of ESCC did not increase with the severity of gastric
      atrophy. Therefore, a causal relationship seems unlikely. Confounding factors,
      such as smoking, may explain both associations.

PMID- 19107938
TI  - Evolutionary morphology of the Tenrecoidea (Mammalia) hindlimb skeleton.
AB  - The tenrecs of Central Africa and Madagascar provide an excellent model for
      exploring adaptive radiation and functional aspects of mammalian hindlimb form.
      The pelvic girdle, femur, and crus of 13 tenrecoid species, and four species from
      the families Solenodontidae, Macroscelididae, and Erinaceidae, were examined and
      measured. Results from qualitative and quantitative analyses demonstrate
      remarkable diversity in several aspects of knee and hip joint skeletal form that
      are supportive of function-based hypotheses, and consistent with studies on
      nontenrecoid eutherian postcranial adaptation. Locomotor specialists within
      Tenrecoidea exhibit suites of characteristics that are widespread among
      eutherians with similar locomotor behaviors. Furthermore, several characters that
      are constrained at the subfamily level were identified. Such characters are more
      indicative of postural behavior than locomotor behavior.

PMID- 19107939
TI  - Osteology of Paedocypris, a miniature and highly developmentally truncated fish
      (Teleostei: Ostariophysi: Cyprinidae).
AB  - Species of the cyprinid genus Paedocypris are among the smallest and most
      developmentally truncated fishes and vertebrates. Our analysis of their skeletal
      structure reveals a puzzling combination of extreme developmental truncation and
      an increased morphological complexity in sexually dimorphic characters. The
      skeleton of Paedocypris is characterized by reduction and loss and resembles in
      many aspects that of a larval/early juvenile stage of its close relatives. We
      found 61 characters that have been affected by developmental truncation. A
      comparison with the skeletal development of a close relative, the zebrafish Danio
      rerio, demonstrates that the majority of the absent bones or skeletal structures
      in Paedocypris are those that appear late in the ossification trajectory of the
      zebrafish. Thus, their absence in Paedocypris seems to be due to the simple
      developmental truncation of terminal stages in the ossification sequence. Our
      study of the sexually dimorphic structures in Paedocypris demonstrates that
      predominantly the male exhibits the more complex state. In relation to the
      female, male Paedocypris uniquely possess a cleithrum with a pointed posterior
      process that covers the scapula laterally, and a more medially situated posterior
      flange that contacts the dorsal area of the coracoid; a massive and heavily
      ossified uppermost pectoral radial tightly bound to the scapula; thickened and
      enlarged three uppermost pectoral-fin rays; a large triangular, dorsolaterally
      directed process on the outer arm of the massive os suspensorium; and a enlarged
      and shovel-like anterodorsally directed basipterygium; and a hypertrophied first
      pelvic-fin ray with additional anterior flanges that support keratinized pads of
      skin. Female Paedocypris show only one structure that is better developed than in
      males: the first proximal-middle radial and the anteriormost fin ray of the
      dorsal fin are more massive and more heavily ossified. Although the function and
      biological role of these dimorphisms is still unknown, we hypothesize that they
      are related to a special reproductive behavior. Paedocypris is a prime example
      for the recent claim that miniaturization among cyprinids is associated with
      evolutionary novelty only in developmentally truncated miniatures and not in
      proportioned dwarfs. Paedocypris offers a strong challenge to Schindleria as the
      most extreme example of developmental truncation known among fishes. We highlight
      the difficulties that developmentally truncated taxa frequently pose to the
      resolution of their phylogenetic position and propose an approach to overcome
      this problem. Our phylogenetic comparison to determine the systematic position of
      Paedocypris among cyprinids reveals that it shares not only a number of unique
      absences, but also highly unusual progressive characters with Sundadanio and
      Danionella, two other Asian miniature cyprinids. We hypothesize that the three
      genera form a monophyletic group. We further found that Paedocypris and
      Danionella share a number of uniquely derived characters pointing to a sister
      group relationship of the two.

PMID- 19107940
TI  - Morphology of the skull of the white-nosed blindsnake, Liotyphlops albirostris
      (Scolecophidia: Anomalepididae).
AB  - This article presents a detailed description and illustration of the skull of
      Liotyphlops albirostris in comparison to the skulls of Typhlophis squamosus,
      Leptotyphlops dulcis, and Typhlops jamaicensis, based on high-resolution X-ray
      computed tomography (HRXCT). The skull of T. squamosus is illustrated and
      discussed in detail for the first time. A number of uniquely shared derived
      characters is identified that support the monophyly of the clade Anomalepididae.
      Anomalepidids retain some features that are plesiomorphic relative to other
      scolecophidians, such as the presence of a supratemporal (except in Anomalepis)
      and ectopterygoid. The homology of the element located posteroventral to the
      eyeball in anomalepidids and variably referred to as a jugal or postorbital (or a
      fusion of both in Anomalepis) remains unknown. Scolecophidians exhibit a highly
      derived skull morphology adapted to head-first burrowing. Both anomalepidids and
      typhlopids evolved a condition known as an "outer shell design," but did so in
      different ways. Leptotyphlopids combine elements of both the anomalepidid and
      typhlopid snout morphologies.

PMID- 19107941
TI  - Choanocyte ultrastructure in Halisarca dujardini (Demospongiae, Halisarcida).
AB  - Understanding poriferan choanocyte ultrastructure is crucial if we are to unravel
      the steps of a putative evolutionary transition between choanoflagellate protists
      and early metazoans. Surprisingly, some aspects of choanocyte cytology still
      remain little investigated. This study of choanocyte ultrastructure in the
      halisarcid demosponge Halisarca dujardini revealed a combination of minor and
      major distinctive traits, some of them unknown in Porifera so far. Most
      significant features were 1) an asymmetrical periflagellar sleeve, 2) a battery
      of specialized intercellular junctions at the lateral cell surface complemented
      with an array of lateral interdigitations between adjacent choanocytes that
      provides a particular sealing system of the choanoderm, and 3) a unique,
      unexpectedly complex, basal apparatus. The basal apparatus consists of a basal
      body provided with a small basal foot and an intricate transverse skeleton of
      microtubules. An accessory centriole, which is not perpendicular to the basal
      body, is about 45 degrees . In addition, a system of short striated rootlets
      (periodicity = 50-60 nm) arises from the proximal edge of the basal body and runs
      longitudinally to contact the nuclear apex. This is the first flagellar rootlet
      system ever found in a choanocyte. The accessory centriole, the rootlet system,
      and the nuclear apex are all encircled by a large Golgi apparatus, adding another
      distinctive feature to the choanocyte cytology. The set of distinct features
      discovered in the choanocyte of H. dujardini indicates that the ultrastructure of
      the poriferan choanocyte may vary substantially between sponge groups. It is
      necessary to improve understanding of such variation, as the cytological features
      of choanocytes are often coded as characters both for formulation of hypotheses
      on the origin of animals and inference of phylogenetic relationships at the base
      of the metazoan tree.

PMID- 19107942
TI  - Trophic apparatus in cyprinodontiform fishes: functional specializations for
      picking and scraping behaviors.
AB  - Cyprinodontiforms are a diverse and speciose order that includes topminnows,
      pupfishes, swordtails, mosquitofishes, guppies, and mollies. Sister group to the
      Beloniformes and Atheriniformes, Cyprinodontiformes contains approximately twice
      the number of species of these other two orders combined. Recent studies suggest
      that this group is well suited to capturing prey by "picking" small items from
      the water surface, water column, and the substrate. Because picking places
      unusual performance demands on the feeding apparatus, this mode of prey capture
      may rely upon novel morphological modifications not found in more widespread ram-
      or suction-based feeding mechanisms. To assess this evolutionary hypothesis, we
      describe the trophic anatomy of 16 cyprinodontiform species, selected to broadly
      represent the order as well as capture intrageneric variation. The group appears
      to have undergone gradual morphological changes to become increasingly
      specialized for picking and scraping behaviors. We also identify a suite of
      functional characters related to the acquisition of a novel and previously
      undescribed mechanism of premaxillary protrusion and retraction, including:
      modification of the "premaxillomandibular" ligament (which connects each side of
      the premaxilla to the ipsilateral mandible, or lower jaw), a novel architecture
      of the ligaments and bony elements that unite the premaxillae, maxillae and
      palatine bones, and novel insertions of the adductor muscles onto the jaws. These
      morphological changes to both the upper and lower jaws suggest an evolutionary
      trend within this group toward increased reliance on picking individual prey from
      the water column/substrate or for scraping encrusting material from the
      substrate. We propose that the suite of morphological characters described here
      enable a functional innovation, "picking," which leads to novel trophic habits.

PMID- 19107943
TI  - Risk of prostate cancer among Swedish-born and foreign-born men in Sweden, 1961
      2004.
AB  - To elucidate the importance of environmental and genetic factors in prostate
      cancer etiology, we compared the risk of prostate cancer among foreign-born men
      to that of Swedish-born men in Sweden and to that in the country of origin. We
      estimated rate ratios (RRs) with 95% confidence intervals (CIs) adjusted for age,
      calendar period of year and education using Poisson regression in a cohort of 3.8
      million men aged 45 years and older between 1961 and 2004. During the 45 years of
      follow-up, 8,244 and 187,675 cases of prostate cancer occurred among foreign-born
      and Swedish-born men, respectively. Overall, foreign-born men had a significantly
      40% decreased risk of prostate cancer compared to Swedish-born men (RR = 0.62,
      95% CI = 0.61-0.63). Men born in Middle Africa and in the Caribbean had an
      increased risk (RR = 1.89, 95% CI = 0.95-3.78 and RR = 1.24, 95% CI = 0.71-2.19,
      respectively). The overall risk in both strata of duration of residence or age at
      immigration was lower among immigrants compared to Swedish-born men. After
      additional adjustment for birthplace and age at immigration, although the risk
      remained lower among immigrants compared to Swedish-born, but it was increased
      among immigrants who stayed 35 years and longer compared to those who stayed
      shorter (RR = 1.33, 95% CI = 1.21-1.46). Both environmental and genetic factors
      seem to be involved in the etiology of prostate cancer. Duration of residence was
      an important factor affecting the risk among immigrants. Studies focusing on the
      etiology of prostate cancer specifically in African immigrants and their
      descendants and increasing preventive and diagnostic activities on old immigrants
      are recommended.

PMID- 19107944
TI  - Mechanisms involved in the down-regulation of TCR zeta chain in tumor versus
      peripheral blood of oral cancer patients.
AB  - Immune dysfunction is the hallmark of patients with oral cancer. Down-regulation
      of T cell receptor (TCR) zeta chain expression was observed in T cells from
      patients with oral squamous cell carcinoma. In peripheral blood, the decrease in
      TCR zeta chain showed an inverse correlation with the tumor stage as demonstrated
      by western blotting, confocal microscopy and flow cytometry. The mechanism of TCR
      zeta chain degradation in the peripheral blood involves ubiquitination and
      subsequent targeting of TCR zeta for degradation in the lysosome. Decreased
      expression of PKC theta and the subsequent decrease of TCR zeta chain
      transcription factor Elf-1 and its binding to DNA may contribute to the
      decreased/or absent TCR zeta chain transcripts in the tumor infiltrating
      lymphocytes. Oral cancer patients exhibiting TCR zeta chain defect also showed
      impaired lymphocyte proliferation, cytokine profile and intracellular calcium
      release upon stimulation with anti CD3 mAb. Our data shows that posttranslational
      degradation is primarily responsible for decreased TCR zeta chain expression in
      the peripheral blood, while a transcriptional defect is observed in the tumor
      compartment. The down-regulation of TCR zeta chain culminates into impaired
      lymphocyte responses in these patients.

PMID- 19107945
TI  - Pretreatment FDG-PET standardized uptake value as a prognostic factor for outcome
      in head and neck cancer.
AB  - BACKGROUND: We studied the potential prognostic significance of pretreatment 18
      fluorodeoxyglucose-positron emission tomography (FDG-PET) standardized uptake
      value (SUV) in squamous cell carcinoma of the head and neck (SCCHN). METHODS: A
      retrospective review of the pretreatment FDG-PET scans of 60 patients with SCCHN
      was performed. All patients received radiotherapy and 37 also received concurrent
      chemotherapy. SUV was calculated by 2 nuclear-medicine physicians who were
      blinded to the clinical data. Disease-free survival (DFS) was analyzed with
      respect to SUV (and other potential prognostic factors). RESULTS: The median SUV
      was 7.2 (range, 1-24.7); 34 patients (57%) had SUV < 9.0 compared with 26
      patients (43%) with an SUV > or = 9.0. The group with low SUV had significantly
      better 2-year DFS compared with the high SUV group (72% vs 37%), p = .007. On
      multivariate analysis, stage and age were also associated with DFS, but SUV
      remained an independent predictor of DFS (hazard ratio: 1.08; p = .016).
      CONCLUSION: SUV was significantly associated with outcome after modern definitive
      therapy of SCCHN.

PMID- 19107946
TI  - Quality-adjusted survival analysis of Radiation Therapy Oncology Group (RTOG) 90
      03: phase III randomized study comparing altered fractionation to standard
      fractionation radiotherapy for locally advanced head and neck squamous cell
      carcinoma.
AB  - BACKGROUND: To evaluate quality-adjusted survival (QAS) of patients with locally
      advanced squamous cell carcinoma of the head and neck treated with 4 different
      radiation fractionation schedules. METHODS: QAS was calculated using the quality
      adjusted time without toxicity or relapse (Q-TWiST) methodology. Utilities
      (patient preferences for certain health states) were obtained by threshold
      analysis. Q-TWiST therefore equaled TWiST + ([weight for toxicity] x [time spent
      in toxicity]) + ([weight for relapse] x [time spent in relapse]). RESULTS: A
      statistically significant increase in QAS existed for patients treated with
      hyperfractionated radiotherapy compared with standard fractionated radiotherapy
      (SFX) with a toxicity utility > or = 0.57 and relapse utility < or = 0.72. No
      statistically significant difference was observed for patients treated with the
      other 2 fractionation schedules compared with SFX. CONCLUSION: Q-TWiST analysis
      identified patient groups that would benefit from more aggressive therapy.
      Further investigation with patient-generated utilities is needed.

PMID- 19107947
TI  - Comparison of outcome measures in head and neck cancer--literature review 2000
      2006.
AB  - BACKGROUND: The aim of this study was to systematically analyze outcome measures
      in head and neck cancer trials using the International Classification of
      Functioning. Disability, and Health (ICF) as reference. METHODS: Clinical trials
      2000 to 2006 in MEDLINE were selected according to predefined criteria. Outcome
      measures were extracted, and concepts contained in the outcome measures were
      translated into ICF. RESULTS: A total of 254 publications showed 4203 concepts
      that translate into 117 different, second-level ICF-categories. Just 2 of 117
      outcome measures apply regularly: e580 (health_services) in 58% publications and
      b510 (ingestion_function) in 46% publications. Any other outcome measure applies
      to < 33% publications. In the differentiation of outcome measures among tumor
      locations, staging, or treatment options, no systematic use of specific outcome
      measures was identified in any subgroup. CONCLUSION: The ICF provides a useful
      reference to identify and quantify outcome measures in head and neck
      cancertrials. Applying the ICF classification reveals little standardization in
      the use of outcome-measures by different authors. However, this is not related to
      the heterogeneity of head and neck cancer in terms of tumor locations, staging,
      or treatment options. Systematic use of the ICF might increases comparability of
      study results and decrease data silos.

PMID- 19107948
TI  - Phase III randomized study: oral pilocarpine versus submandibular salivary gland
      transfer protocol for the management of radiation-induced xerostomia.
AB  - BACKGROUND: Xerostomia is a serious morbidity of radiation treatment in head and
      neck cancer. METHODS: We conducted a prospective phase III multicenter randomized
      study comparing submandibular salivary gland transfer (SGT) procedure with
      pilocarpine during and for 3 months after XRT. Salivary flow (baseline,
      stimulated) and University of Washington Quality of Life Questionnaire (U of W
      QOL) scores were measured. RESULTS.: An interim intent to treat analysis (120
      patients) at 6 months shows superior results in SGT arm: median baseline salivary
      flow for SGT (0.04 mL/minute) versus pilocarpine (0.01 mL/minute), p = .001;
      median stimulated salivary flow (0.18 mL/minute) for SGT versus (0.05 mL/minute)
      for pilocarpine, p = .003. Scores (U of W QOL) for amount (p = .017) and
      consistency of saliva (p = .005) in favor of SGT leading to premature closure of
      study. CONCLUSIONS: Submandibular SGT procedure is superior to pilocarpine in
      management of radiation-induced xerostomia.

PMID- 19107949
TI  - Effect of induction chemotherapy on speech and swallowing function in patients
      with oral tongue cancer.
AB  - BACKGROUND: Swallowing physiology, diet, and patient-reported outcomes were
      evaluated after induction chemotherapy for oral tongue cancer. METHODS: Fifteen
      of 23 patients enrolled in a phase II clinical trial of induction chemotherapy
      followed by surgical resection for oral tongue cancer underwent instrumental and
      perceptual analysis of speech and swallowing. Oropharyngeal swallow efficiency
      (OPSE) was calculated. Patient-reported outcomes were collected. We compared pre-
      and postchemotherapy results. RESULTS: OPSE scores were not significantly
      different (p > .05) after induction chemotherapy; however, patient-reported
      swallowing and diet levels were significantly higher (p < .001 and p = .015,
      respectively). Diet levels improved from soft-chewable to full diet in most
      patients. Speech intelligibility did not change (p = .328). CONCLUSION: It
      appears that induction chemotherapy has a negligible effect on speech and
      swallowing physiology but may provide symptomatic improvement of pain and
      swallowing after treatment. Further investigations are needed to corroborate
      these findings.

PMID- 19107950
TI  - Place and value of the recurrent laryngeal nerve (RLN) palpatory method in
      preventing RLN palsy during thyroid surgery.
AB  - BACKGROUND: In recent years, certain publications have appeared confirming that
      intraoperative palpation of the recurrent laryngeal nerve (RLN) is a very
      reliable method. METHOD: The characteristics of the surgical anatomy of 1023 RLN
      have been summarized on the basis of intraoperative palpability, running down,
      branching variations, thickness, and laryngeal entry site. RESULTS: Palpation was
      helpful in 81.4% (833/1023), proved false positive in 8.2% (84/1023), and in
      10.4% (106/1023) it was of no help in the exact localization. Definitive RLN
      palsy was experienced in 0.78% of all cases (8/1023), while transient paresis was
      encountered in 1.2% (12/1023). Only a moderately strong stochastic correlation
      could be found between RLN palsies and those nerves which were nonpalpable and
      atypical, which showed the joint occurrence of being both thinner than normal and
      branching already before the plane of the inferior thyroid artery (Cramer's
      associate coefficient, C = 0.383). CONCLUSION: Palpation alone cannot substitute
      visualization and proper surgical dissection of the nerve.

PMID- 19107951
TI  - Aurora kinase A inhibition and paclitaxel as targeted combination therapy for
      head and neck squamous cell carcinoma.
AB  - BACKGROUND: Aurora kinase A (AURKA) is amplified with varying incidence in
      multiple human cancers including head and neck squamous cell carcinoma (HNSCC).
      We investigated whether AURKA is a potential therapeutic target in HNSCC.
      METHODS: We conducted an immunohistochemical analysis of AURKA expression in
      paired normal and tumor samples (n = 63). HNSCC cells treated with siRNA specific
      for AURKA were assessed for AURKA mRNA and protein expression levels by reverse
      transcriptase-polymerase chain reaction and Western blot analysis. Tumor cells
      treated with siRNA and paclitaxel were assessed for cell proliferation by MTT
      assay and for cell cycle distribution by flow cytometry. RESULTS: AURKA
      expression was higher in tumor than in adjacent normal in most (85%) of the
      samples analyzed. HNSCC cells and primary tumors revealed high expression levels
      of AURKA. Most primary tumors also showed high kinase activity of the enzyme.
      Targeted AURKA inhibition increased the sub-G1 cell fraction, with a concomitant
      reduction in the G1 cell population, indicating induction of apoptosis and thus
      markedly suppressed proliferation of HNSCC cells. Combining siRNA-induced AURKA
      inhibition with 5 to 10 nM paclitaxel synergistically enhanced apoptosis
      induction. CONCLUSION: AURKA is a potential therapeutic target for HNSCC. Further
      investigation of small-molecule AURKA inhibitors as therapeutic agents is
      warranted.

PMID- 19107952
TI  - Developmental toxicity associated with receptor tyrosine kinase Ret inhibition in
      reproductive toxicity testing.
AB  - BACKGROUND: Urogenital abnormalities are among the most common of all human birth
      defects. In developmental toxicity studies with the Syk kinase inhibitor R788, a
      spectrum of findings, including renal agenesis, were observed. R788 has also been
      found to inhibit the receptor tyrosine kinase Ret. Ret kinase is known to be an
      essential component in the signaling pathway required for renal organogenesis and
      ureteric duct formation. Previously known is that mutant mice without the c-ret
      gene, develop urogenital malformations including renal agenesis. METHODS: In GLP
      developmental toxicity studies, gravid rabbits were treated orally with R788 at
      doses of 0, 10, 22, and 50 mg/kg/day (gestation days 7-19) and gravid rats
      received 0, 5, 12.5, and 25 mg/kg/day (gestation days 6-17) by the same route.
      The activity of R406 against Ret kinase was assessed in biochemical and cell
      based assays. RESULTS: A dose-dependent increase in malformations, including
      renal and ureteric agenesis and a specific major vessel anomaly, retroesophageal
      right subclavian artery, was observed in both the rat and rabbit. R788 proved to
      be a potent inhibitor of Ret kinase. CONCLUSIONS: R788 promoted a spectrum of
      developmental toxicity, including renal and ureteric agenesis and a specific
      major vessel abnormality, retroesophageal right subclavian artery, in two
      different species. These effects are likely the result of inhibition of Ret
      kinase given its importance in the normal ontogeny of the urogenital and
      cardiovascular systems across species.

PMID- 19107953
TI  - Pregnancy exposure registries: academic opportunities and industry
      responsibility.
AB  - Pregnancy exposure registries systematically evaluate pregnancies and outcomes
      exposed to a medicinal compound or device during the gestational period.
      Historically, such programs partner an academic institution with one or more
      pharmaceutical companies or are run solely by a pharmaceutical company. However,
      other examples abound. This article describes what a pregnancy exposure registry
      is, as well as selected methodological challenges they face, using real examples
      and applications.

PMID- 19107954
TI  - Determination of human teratogenicity by the astute clinician method: review of
      illustrative agents and a proposal of guidelines.
AB  - BACKGROUND: The determination that an exposure is a human teratogen is a complex
      process involving the application of the principles of teratology, epidemiology,
      biology, and clinical medicine. Shepard suggested that the "rare exposure/rare
      defect" or "case report method", the astute clinician model, was one approach for
      establishing teratogenicity. The purpose of this article is to review selected
      exposures with the goal of identifying principles that lead to a working proposal
      for the application of this approach. METHODS: We selected three known exposures-
      penicillamine, fluconazole and mycophenolate mofetil--for detailed review. These
      agents were chosen because their evidence for causation arises mostly from
      clinical observations in the context of biologic plausibility. RESULTS: All three
      agents were originally detected based on astute observations by clinicians
      reporting on individual cases of a distinctive pattern of malformation or, in the
      case of penicillamine distinctive phenotype, after the rare exposure. All three
      have varying degrees of biologic evidence that support the hypothesis that each
      represents a human teratogen. All three meet Shepard's criteria for "proof."
      CONCLUSIONS: The basic premise of this approach depends on the rarity of both the
      exposure and the outcome. We propose guidelines for utilization of this approach
      in the determination of human teratogenicity.

PMID- 19107955
TI  - Genetic tools and algorithms for gene discovery in major congenital anomalies.

PMID- 19107957
TI  - Clinical geneticists in birth defects surveillance and epidemiology research
      programs: past, present and future roles.
AB  - Clinical geneticists have contributed to the creation and operation of birth
      defects surveillance systems and epidemiology research programs. Over the years,
      many continue to assist the multidisciplinary staff at state-based and regional
      programs, national networks, and international databases. Currently, all centers
      participating in the National Birth Defects Prevention Study include a clinical
      geneticist, which has increased awareness of this role. It is generally assumed
      that the medical skills and expertise acquired from clinical practice of a
      clinical geneticist can assist in the tasks of record review, case
      classification, coding, staff education, peer networking, and research, but these
      activities have not been formally reviewed. To increase the general knowledge
      base, this article used the framework of an historical descriptive review
      focusing on a sample of birth defects surveillance systems presented as
      illustrative case studies. We examined the contribution of clinical geneticists
      to a sample of epidemiologic research studies from each program. Looking to the
      future, we discuss the education of other clinical geneticists, the need to
      evaluate performance, and the geneticist's participation with other public health
      colleagues in the shared goal of birth defects prevention.

PMID- 19107956
TI  - Isolated fetal omphalocele, Beckwith-Wiedemann syndrome, and assisted
      reproductive technologies.
AB  - OBJECTIVE: To assess the frequency of Beckwith-Wiedemann syndrome (BWS) among
      fetuses with an ultrasound diagnosis of isolated omphalocele and to examine
      relevant clinical variables, in particular route of conception. MATERIALS AND
      METHODS: An ultrasound and consultation database (1988-2007) was searched and
      cases were included that met the following criteria: omphalocele, no additional
      major structural anomaly or autosomal aneuploidy, and either newborn examination
      or molecular diagnostic studies for BWS. Medical records were reviewed and a
      nested case-control analysis matching day of birth assessed the route of
      conception, given the changing prevalence of assisted reproduction during the
      study period. RESULTS: Thirty cases of isolated omphalocele were identified.
      Beckwith-Wiedemann syndrome was diagnosed in six cases (6/30 [20.0%]); four by
      newborn examination (4/6) and two on prenatal molecular studies (2/6). Of note,
      one case of BWS had a karyotype of 47,XXX, the remainder was euploid. Compared
      with isolated omphaloceles, fetuses with BWS more often were twins (3/6 vs. 1/24;
      p < 0.001), had polyhydramnios (4/6 vs. 2/24; p < 0.001), were macrosomic at
      birth (3/6 vs. 4/24 p < 0.001), and had been conceived by assisted reproduction
      (3/6 vs. 2/22; p = 0.04). When compared with normal controls matched by date of
      birth, conception by assisted reproductive technique among BWS births was highly
      significant, (p < 0001). CONCLUSIONS: Beckwith-Wiedemann syndrome is present in a
      noteworthy portion of fetuses with isolated omphalocele on ultrasound, and
      prenatal molecular studies are warranted. Even among this small cohort, a
      recurring theme of conception by assisted reproduction exists.

PMID- 19107958
TI  - Better data needed from pregnancy registries.
AB  - This article is a consensus position statement from the Research Committee of the
      Organization of Teratology Information Specialists (OTIS). The Committee believes
      that more specific information on the timing and dose of drug exposures from
      pregnancy birth defect registries sponsored by pharmaceutical companies (herein
      called pregnancy registries) would improve the estimation of risk for
      developmental toxicity (i.e., growth alteration, structural anomalies,
      functional/neurobehavioral deficits, or death). Specifically, the Committee
      believes that the exposure timing should be stated in gestational weeks and days
      rather than simply weeks. In addition, the Committee believes that the exposure
      dose should be stated in patient-specific terms, such as body weight (mg/kg) or
      body surface area (mg/m(2)) rather than simply dose strength. Although the focus
      of this position is pregnancy registries, it also is applicable to any source of
      medication-induced embryo-fetal toxicity.

PMID- 19107959
TI  - DSCG reduces RSV-induced illness in RSV-infected mice.
AB  - Respiratory syncytial virus (RSV) is one of the pathogens generally associated
      with the common cold, lower respiratory infection, and exacerbation of asthma.
      Disodium cromoglycate (DSCG) is a safe and widely used drug for the prevention of
      bronchial asthma and allergic rhinitis attacks. The effect of DSCG on acute upper
      respiratory tract viral infections remains controversial. The purpose of the
      study was to investigate the effects of DSCG on parameters of RSV induced
      illness. Using a well-characterized murine model of RSV infection, the effect of
      DSCG on RSV-induced illness was evaluated by body weight, respiratory function,
      viral replication, level of IFN-gamma in lungs, serology, and histopathology.
      Mice treated with DSCG were protected against RSV-induced weight loss. The
      baseline Penh in RSV-infected mice treated with DSCG was less than that in mice
      treated with saline. In methacholine challenge, the increase in Penh in RSV
      infected mice treated with DSCG was suppressed to the same level as that in the
      mock-infected group. Further, there were no differences in viral replication
      between the mice treated with DSCG and those treated with saline, and the level
      of inflammation observed in the lungs in RSV-infected mice treated with DSCG was
      not as severe as that in mice treated with saline. These findings indicate that
      DSCG may be an effective agent for the prevention of RSV induced disease and the
      relief of symptoms of RSV infection.

PMID- 19107960
TI  - Case report: Eastern equine encephalitis virus imported to the UK.
AB  - Eastern equine encephalitis (EEE) is rare, but the most severe of the mosquito
      borne encephalitides in the United States with a high case fatality rate of 30%.
      Here, we present a patient with EEE. EEE virus causes sporadic human disease in
      the Eastern parts of the United States, but the case we describe was a Scottish
      tourist who acquired the disease from mosquito bites while in holiday in the
      United States. This is a first report of an imported case to Europe.

PMID- 19107961
TI  - Molecular characterization of rotaviruses, noroviruses, sapovirus, and
      adenoviruses in patients with acute gastroenteritis in Thailand.
AB  - Outbreaks of viral gastroenteritis occur worldwide including Thailand.
      Unfortunately, there is limited information since etiologic agents have not been
      identified in several outbreaks of nonbacterial gastroenteritis. The genotype of
      enteric viruses causing acute gastroenteritis in Thailand was determined using
      reverse transcription-multiplex polymerase chain reaction and DNA sequencing.
      From January 2006 to February 2007, stool samples were collected from patients
      with acute gastroenteritis of all age groups attending a hospital in Thailand,
      and patients with nonbacterial acute gastroenteritis (262 patients) were tested
      for enteric viruses. The overall positive detection rate of enteric viruses was
      14.9%; group A rotaviruses (6.1%), noroviruses (6.5%): GI (0.8%) and GII (5.7%),
      adenoviruses (1.5%), and sapoviruses (0.8%) were found. Group B and C
      rotaviruses, and astroviruses were not detected in the enrolled patients. Viral
      acute gastroenteritis occurred in children less than 15 years of age (25.2%,
      33/131) with higher frequency than in adults (4.6%, 6/131), P-value <0.001.
      Rotavirus G1 was the most predominant genotype, followed by G3, and G9. Among
      noroviruses, GI-2 was identified; whereas, GII was predominant with a high
      frequency of GII-4 observed, followed by GII-16, GII-2, GII-3, and GII-12.
      Sapovirus GII-3 and human adenoviruses were identified. This study suggests that
      enteric viruses play an essential role in patients with acute gastroenteritis
      attending hospital and mainly in children who have a higher prevalence of group A
      rotaviruses and noroviruses. The genetic analyses provide molecular
      epidemiological data for viruses important to public health.

PMID- 19107962
TI  - Typing of human papillomavirus in women with cervical lesions: prevalence and
      distribution of different genotypes.
AB  - Human papillomavirus (HPV) are distributed widely and persistent infection with
      high-risk (HR) HPV is recognized as a necessary cause of cervical cancer. The aim
      of this study was to evaluate the distribution of different HR-HPV genotypes in
      199 women with cervical pre-invasive lesions undergoing conservative treatment. A
      Linear Array HPV Genotyping Test was used to identify individual HPV genotypes in
      cervical samples. It was observed that the most prevalent HPV genotypes were HPV
      16 (52.6%), HPV 51 (13.5%), and HPV 31 (10.9%); HPV 18 was found in 7.3% of the
      patients. Stratifying the different HPV genotypes according to the severity of
      the cervical lesion, a strong association between the increasing severity of the
      histological diagnosis and the detection of more carcinogenic HR-HPV type was
      found, and in all but one cervical intraepithelial neoplasia of grade 3 the
      presence of at least one HR-HPV could be detected, with more than 70% of cervical
      intraepithelial neoplasia of grade 3 patients bearing HPV 16. Multiple
      infections, comprising between 2 and 6 HPV types, were found in 43% of patients;
      however, the presence of more than 1 HR-HPV type was not associated with an
      increased risk of high grade lesions. In conclusion, this data show that HPV 16,
      51, 31, 52, and 18 were the prevalent types found in patients with cervical
      lesion undergoing conservative treatment, with a high prevalence of HPV 16 in
      cervical intraepithelial neoplasia of grade 3 patients. No association between
      multiple infection and severity of the lesion could be found.

PMID- 19107963
TI  - Characterization of genotype P[9]G12 rotavirus strains from Argentina: high
      similarity with Japanese and Korean G12 strains.
AB  - The circulation of the unusual P[9]G12 strains was previously reported in
      suburban Buenos Aires, Argentina and in Far Eastern Asian countries. To examine
      genetic relationships of these strains the genes coding VP7, VP4, and NSP1 from
      two Argentine, one Japanese and one Korean P[9]G12 isolates were sequenced and
      their overall genome relatedness was determined by liquid hybridization. In
      addition, liquid hybridization was used to compare this group of strains to the
      previous G12 isolates L26 and Se585, and prototype Wa, DS-1, and AU-1 strains.
      The genomes of the Argentinean, Japanese and Korean strains were virtually
      indistinguishable by hybridization assays, suggesting very high sequence
      relatedness for all 11 segments. Hybridization assays also demonstrated that
      these four strains belong to the AU-1 genogroup and that their genetic
      relationship with rotaviruses L26 and Se585 is limited to the VP7 gene. The VP7,
      VP4, and NSP1 genes of the Argentinean, Japanese and Korean strains were highly
      homologous to each other and to Thai strain T152 ( approximately 99% identity).
      These results together with the report of a similar strain detected during 2003
      in Brazil are consistent with a recent importation and dissemination of the G12
      strains from Far Eastern countries into South America. Increasing reports from
      several regions of the world demonstrating a variety of different G12 reassortant
      strains suggests that routine surveillance for this serotype should be conducted
      to determine its potential for global emergence.

PMID- 19107964
TI  - Phylogenetic analysis of rotaviruses with predominant G3 and emerging G9
      genotypes from adults and children in Wuhan, China.
AB  - Prevalence and phylogenetic relatedness of rotaviruses causing diarrheal diseases
      in children and adults were analyzed in Wuhan, China. During a period between
      June 2006 and February 2008, group A rotavirus was identified in 24.9% (280/1126)
      and 7.6% (83/1088) of specimens taken from children and adults, respectively.
      G3P[8] was the most frequent genotype in both children (66.3%) and adults
      (62.7%), followed by G1P[8] (20.3% and 26.2%, respectively). G9 was detected in
      specimens from six children (2.0%) and seven adults (5.6%). The VP7 genes of
      G3P[8] rotaviruses from children and adults showed extremely high sequence
      identities to each other (98.9-100%) and also to those of G3 viruses isolated in
      Wuhan in 2003-2004. In the phylogenetic analysis of the VP7 gene, the G3P[8]
      rotaviruses in Wuhan were clustered into a single lineage with some G3 viruses,
      which had been referred to as "the new variant G3" rotaviruses, reported recently
      in East Asia and Southeast Asia. Similar to G3P[8] rotaviruses, extremely high
      sequence identities between children and adults were observed for VP7 genes of G1
      and G9 rotaviruses. The G9 viruses were clustered in the lineage of globally
      spreading strains, while G1 viruses were genetically close to those reported
      previously in China and Japan. These findings indicated the persistence of the
      variant G3 rotaviruses and spread of G9 rotaviruses derived from the global G9
      lineage in Wuhan, and suggested that the rotaviruses were circulating among
      children and adults, irrelevant to the G types.

PMID- 19107965
TI  - Prevalence of tick-borne encephalitis virus in Ixodes ricinus from a novel
      endemic area of North Eastern Italy.
AB  - In Alpine area of extreme North Eastern Italy the first autochthonous case of TBE
      was reported in 1998 and was followed by 45 cases during the period 2001-2007,
      thus defining this area as definitely endemic. An ecological survey evaluated the
      tick density and the Tick-borne encephalitis virus (TBEV) infection prevalence in
      tick collected in selected sites. In addition, TBE strains were characterized by
      sequencing and phylogenetic analysis. Overall, 2,361 ticks (2,198 nymphs and 163
      adults) of the Ixodes ricinus L. species collected during 2005 and 2006 were
      examined. Five samples were positive for TBEV, corresponding to an overall
      prevalence rate of 0.21%. When analyzed by place, TBEV was discovered in three
      sites where the highest tick density was found. The difference of prevalence
      between high and low density areas tested to be statistically significant (P =
      0.028). Phylogenetic analysis showed that four sequences clustered with the
      Neudoerfl prototype, while the other clustered with the Isosaari 17 strain and
      with a number of Slovenian isolates. In addition, a sequence detected in archival
      samples from one human case segregated with another variant, namely the Swedish
      Toro strain.

PMID- 19107966
TI  - LTR real-time PCR for HIV-1 DNA quantitation in blood cells for early diagnosis
      in infants born to seropositive mothers treated in HAART area (ANRS CO 01).
AB  - HIV-1 diagnosis in babies born to seropositive mothers is one of the challenges
      of HIV epidemics in children. A simple, rapid protocol was developed for
      quantifying HIV-1 DNA in whole blood samples and was used in the ANRS French
      pediatric cohort in conditions of prevention of mother-to-child transmission. A
      quantitative HIV-1 DNA protocol (LTR real-time PCR) requiring small blood volumes
      was developed. First, analytical reproducibility was evaluated on 172 samples.
      Results obtained on blood cell pellets and Ficoll-Hypaque separated mononuclear
      cells were compared in 48 adult HIV-1 samples. Second, the protocol was applied
      to HIV-1 diagnosis in infants in parallel with plasma HIV-RNA quantitation. This
      prospective study was performed in children born between May 2005 and April 2007
      included in the ANRS cohort. The assay showed good reproducibility. The 95%
      detection cut-off value was 6 copies/PCR, that is, 40 copies/10(6) leukocytes.
      HIV-DNA levels in whole blood were highly correlated with those obtained after
      Ficoll-Hypaque separation (r = 0.900, P < 0.0001). A total of 3,002 specimens
      from 1,135 infants were tested. The specificity of HIV-DNA and HIV-RNA assays was
      100%. HIV-1 infection was diagnosed in nine infants before age 60 days. HIV-DNA
      levels were low, underlining the need for sensitive assays when highly active
      antiretroviral therapy (HAART) has been given. The performances of this HIV-DNA
      assay showed that it is adapted to early diagnosis in children. The results were
      equivalent to those of HIV-RNA assay. HIV-DNA may be used even in masked primary
      infection in newborns whose mothers have received HAART.

PMID- 19107967
TI  - Amino acids of Coxsackie B5 virus are critical for infection of the murine
      insulinoma cell line, MIN-6.
AB  - It was shown recently that 15 successive passages of a laboratory strain of the
      Coxsackie B virus 5 in a mouse pancreas (CBV-5-MPP) resulted in apparent changes
      in the virus phenotype, which led to the capacity to induce a diabetes-like
      syndrome in mice. For further characterization of islet cell interactions with a
      passaged virus strain, a murine insulinoma cell line, MIN-6, was selected as an
      experimental model. The CBV-5-MPP virus strain was not able to replicate in MIN-6
      cells in vitro but required adaptation over a few days for progeny production and
      the generation of cytopathic effects. In order to determine the genetic
      characteristics required for virus growth in MIN-6 cells, the whole genome of the
      MIN-6-adapted virus variant was sequenced, and critical amino acids were
      identified by comparing the sequence with that of a virus strain passaged
      repeatedly in the mouse pancreas. The results of site-directed mutagenesis
      demonstrated that only one residue, amino acid 94 of VP1, is a major determinant
      for virus adaptation to MIN-6 cells.

PMID- 19107968
TI  - Genomic diversity of human papillomavirus (HPV) genotype 38.
AB  - Human papillomavirus (HPV) genotype HPV 38 is a HPV genotype associated with skin
      cancer and is classified taxonomically in the beta-PV genus-species 2. At least
      six genomic variants of HPV 38, including prototype isolate and its subtype
      FA125, have been characterized so far. In order to investigate further the
      genomic diversity of HPV 38, a total of 39 HPV 38 positive samples obtained from
      hairs plucked from pubic, scrotal, perianal or eyebrow regions from 31
      immunocompetent healthy male individuals were analyzed. The characterization of
      genomic variants was based on analysis of L1, E6, and E7 genomic regions.
      Sequence analysis revealed the presence of a single genomic variant in 35 samples
      and the presence of at least two different HPV 38 genomic sequences in four
      samples. A total of nine, nine, and five L1, E6, and E7 genomic variants were
      identified among 35 isolates, respectively. After combining nucleotide variations
      in all three genomic regions for a particular isolate, 13 different variants were
      identified, of which 6 and 7 corresponded to HPV 38 and FA125, respectively. In
      addition to 5 genomic variants identified previously (prototype isolate, subtype
      FA125, putative subtype AF091444, isolates U21875 and AF091443), 12 novel genomic
      variants were characterized. A sixth genomic variant described previously
      (L38917) was found to be identical with prototype HPV 38 isolate. Taking into
      account the results of this and previous studies, at least seventeen HPV 38
      genomic variants exist today, 12 of which are described for the first time in
      this study.

PMID- 19107969
TI  - A double-spliced defective hepatitis B virus genome derived from hepatocellular
      carcinoma tissue enhanced replication of full-length virus.
AB  - In hepatitis B virus (HBV) replication cycle, pregenomic RNA undergoes splicing
      and the reverse transcribed defective genomes can be packaged and released.
      Various types of spliced defective HBV genomes have been isolated from the sera
      and liver tissues of viral hepatitis B patients. To explore the functions of a
      2.2 kb double spliced HBV variant, a 3.2 kb full-length HBV isolate (#97-34) and
      its 2.2 kb double-spliced HBV variant (#AP-12) from the tumor tissue of a patient
      with hepatocellular carcinoma (HCC) were amplified and cloned. Sequencing results
      showed that #AP12 had deletions in pre-S2, part of pre-S1, S genes, part of the
      spacer, and part of the reverse transcriptase gene, while the X gene was intact.
      When this defective double-spliced genome and its full-length counterpart genome
      were co-transfected into HepG2 cells, the former was shown to enhance the
      replication of the latter, both by real-time PCR and Southern blotting. When a
      replication incompetent clone 97-34G1881A was used to co-transfect with #AP12,
      #AP12 DNA was increased, indicating that replication of the wild-type virus was
      not the only factor involved in this observation. However, the replication
      enhancing competency of #AP12 was shown to require an intact HBV X expression
      cassette. The double-spliced defective variant might contribute to persistent HBV
      replication in a subpopulation of HCC patients.

PMID- 19107970
TI  - Transmission of hepatitis C virus in an orthopedic hospital ward.
AB  - Healthcare-associated infections with hepatitis C virus (HCV) hitherto have been
      observed mainly in hemodialysis settings as well as in hematology and oncology
      wards. In this communication, molecular and epidemiologic investigations to
      elucidate an HCV outbreak in an orthopedic ward are reported. One hundred and
      thirty-five patients hospitalized in the ward and 104 staff members were tested.
      In addition to extensive epidemiologic reviews and hygienic inspections, direct
      sequencing of HCV PCR fragments and phylogenetic analysis of more than 300
      partial HCV sequences obtained by end-point limiting-dilution real-time PCR assay
      were carried out. Six patients were infected with very closely related HCV
      variants. Patient-to-patient spread of the virus was inferred to have started
      from one patient with previous HCV infection to the other five patients during
      their hospital stay. Inspections did not reveal substantial breaches in basic
      infection control practices and did not identify a specific activity that might
      have led to nosocomial transmission. As a result of the investigations, the
      hospital corrected the documentation of all medical and nursing activities
      undertaken in the ward, abandoned the use of all multidose saline and other
      medication vials, and included explicitly recommendations for the safe
      preparation and administration of injectable drugs into internal infection
      control guidelines. Thereafter, no further nosocomial transmissions of HCV have
      been recorded in the orthopedic ward. The events observed suggest that nosocomial
      transmission of HCV is not limited to hemodialysis, hematology or oncology
      settings, and they also reinforce the mandatory adherence to basic infection
      control practices.

PMID- 19107971
TI  - Prevalence and viral load of oncogenic human papillomavirus types associated with
      cervical carcinoma in a population of North Italy.
AB  - A cross-sectional study was carried out in a population of North Italy to
      determine the prevalence of eight oncogenic human papillomavirus (HPV) types most
      commonly found in cervical carcinoma and to study the relationship between HPV
      DNA loads and severity of disease. A total of 597 cervical samples obtained from
      patients with pathological findings (n = 472) and from women with normal cytology
      (n = 125) were analyzed by means of normalized Real-time PCR assays to quantify
      HPV-16, -18, -31, -45, and -33 group (including -33, -52, -58, -67); the
      normalization of oncogenic HPV viral load was carried out by quantitation of a
      single copy gene. The two most common oncogenic HPV types found were 16 and 31
      (24.3% and 22.9% of pathological samples, respectively); multiple infections were
      demonstrated in 22% of pathological samples. Overall, the HPV total viral load
      was found to increase with increasing severity of associated lesions, although a
      stronger association was observed only for HPV-31 and HPV-16 (gamma = 0.49 and
      0.41, respectively) as compared to HPV-18 and -33 group (gamma = 0.19 and 0.02,
      respectively). However, we found that high levels of HPV-31 or 33 group DNA could
      be prognostic of minor oncogenic risk for high-grade squamous intraepithelial
      lesions (H-SIL) (age adjusted odds ratio [AORs] = 1.57 and 1.26, respectively)
      than HPV-16 and HPV-18 (AORs = 30 and 8, respectively). The AORs also increased
      with HPV total viral load and reached a maximum of AORs = 15.7. Thus, HPV load is
      a type-dependent risk marker for the development of H-SIL.

PMID- 19107972
TI  - Genetic variability of human metapneumovirus isolated from Chilean children, 2003
      2004.
AB  - Human metapneumovirus (hMPV) is a significant cause of acute lower respiratory
      tract infection in all age groups, particularly in children. Two genetic groups
      and four subgroups of hMPV have been described. They co-circulate during an
      epidemic in variable proportions. The aims were to characterize the genotypes of
      hMPV recovered from children hospitalized for acute lower respiratory tract
      infection and to establish the molecular epidemiology of strains circulating in
      Santiago of Chile during a 2-year period. The detection of the N gene by reverse
      transcription polymerase chain reaction was carried out for screening 545 infants
      hospitalized for acute lower respiratory tract infection in Santiago during 2003
      2004. The genetic typing of hMPV was performed by analyzing the fusion gene
      sequences. hMPV was detected in 10.2% (56/545 cases). Phylogenetic analysis of F
      gene sequences from 39 Chilean hMPV strains identified the two groups and four
      subgroups previously described. Strains clustered into group A were split further
      into the sub lineages A1, A2, and A3. Most Chilean strains clustered into the
      proposed novel A3 sub lineage (59%). A3 viruses were present in both years, while
      A1 and A2 circulated just in 1 year. In conclusion, hMPV is a relevant cause of
      acute lower respiratory infection in Chilean children and the potential novel
      cluster of group A emphasize the need for further regional genetic variability
      studies.

PMID- 19107973
TI  - In vitro use of autologous dendritic cells improves detection of T cell responses
      to hepatitis B virus (HBV) antigens.
AB  - T lymphocyte responses to hepatitis B virus (HBV) core antigen (HBcAg) are
      vigorous and easily detectable in vitro during recovery from acute hepatitis B
      but significantly weaker in patients with chronic HBV infection. In contrast, T
      cell responses to hepatitis B surface antigen (HBsAg) are almost undetectable
      during infection and even in a substantial fraction of subjects receiving
      vaccination with HBsAg. The aim of this study was to investigate whether the use
      of dendritic cells (DCs) in an in vitro assay could increase the detection of HBV
      specific T cells in these conditions. Autologous monocyte-derived DCs, compared
      to direct HBsAg addition to the cultures, increased the stimulation of HBs-
      specific T cells. These were detected in 73% of healthy subjects who had recently
      received hepatitis B vaccine and in 43% of patients recovering from acute
      hepatitis B. Likewise, proliferation in response to DC-presented HBcAg was
      detected in both CD4(+) and CD8(+) T cells from the majority of chronic hepatitis
      B patients. A longitudinal evaluation of HBc-specific T cell responses during and
      after a 1-year treatment with pegylated interferon (IFN)-alpha showed that HBc
      specific CD4(+) T cell responses had no correlation with sustained virus
      suppression whereas CD8(+) T cell responses were more frequently detected in
      patients able to control HBV replication after therapy interruption. The use of
      autologous DCs as antigen-presenting cells appears applicable to clinically
      relevant in vitro evaluation of T cell responses, particularly in those
      conditions characterized by low frequency of circulating antigen-specific cells
      and suboptimal in vivo activation.

PMID- 19107974
TI  - HIV-1 seroconversion promotes rapid changes in cervical human papillomavirus
      (HPV) prevalence and HPV-16 antibodies in female sex workers.
AB  - The extent to which human immunodeficiency virus (HIV-1) infection impacts on the
      ability to mount an effective immune response to HPV is unknown, but is relevant
      in planning HPV vaccine strategies for HIV-1 infected individuals. This
      longitudinal study investigated changes shortly after HIV-1 seroconversion on
      cervical HPV types and HPV-16 antibody responses in serum and at the cervix of
      female sex workers. Typing of HPV DNA from cervical cells was done prior to HIV-1
      seroconversion and within 1 year and greater than 2 years after HIV-1
      seroconversion. Antibody determinations on serum and cervico-vaginal rinse
      samples were by HPV-16 virus-like particle-based, enzyme-linked immunosorbent
      assay. Of 104 women tested, 40 (38.4%) became HIV-1 seropositive (HIV-positive)
      during the course of the study. Shortly after HIV-1 seroconversion a significant
      increase in multiple (>1) HPV infection (OR 4.0, 95% CI 1.3-11.9) was observed
      compared with HIV-1 seronegative (HIV-negative) women and certain changes in HPV
      type infection. HIV-1 seroconversion resulted in a reduced prevalence of serum
      HPV-16 IgA and cervico-vaginal IgA and IgG but an increased prevalence of serum
      HPV-16 IgG. All HIV-positive women had been exposed to HPV-16 as all displayed
      serum HPV-16 IgG. Serum HPV-16 responses were maintained at a high magnitude in
      the presence of HPV-16 infection irrespective of HIV infection, but decreased in
      the absence of HPV-16 infection. In conclusion, HIV-1 seroconversion in sex
      workers rapidly increased cervical HPV infection and caused a reduced ability to
      produce cervical HPV-16 antibodies but a continued ability to generate serum IgG
      antibodies.

PMID- 19107976
TI  - Lamivudine monoprophylaxis and adefovir salvage for liver transplantation in
      chronic hepatitis B: a seven-year follow-up study.
AB  - In Asia Pacific countries, lamivudine is used frequently as the sole prophylaxis
      for hepatitis B virus (HBV) recurrence after liver transplantation due to
      financial consideration. The aim was to evaluate the long-term outcome of
      lamivudine monoprophylaxis with adefovir salvage for liver transplantation in
      chronic hepatitis B. Consecutive chronic hepatitis B patients who received liver
      transplantation from 1999 to 2003 and with at least 12 months follow up were
      studied. Lamivudine monotherapy was used for antiviral prophylaxis and adefovir
      was added as salvage treatment for recurrence of HBV. Twenty-four patients were
      followed up for 272 (76-372) weeks post-liver transplantation. HBV recurrence
      developed in seven patients with cumulative probabilities of 8%, 13%, 28%, 35%,
      35%, and 49% in 1, 2, 3, 4, 5, and 6 years. At the time of recurrence of HBV, the
      HBV DNA level was 910,244 (363 to 9 x 10(8)) copies/ml. On direct sequencing,
      four patients had rtM204I mutation and three patients HBV DNA levels were too low
      for sequencing. Six patients had elevated ALT (two patients had ALT >1,000 IU/L
      and jaundice) but none had hepatic encephalopathy. After adefovir treatment for
      150 (91-193) weeks, six (86%) patients had normal ALT. HBV DNA was undetectable
      in two (29%) patients, 100-1,000 copies/ml in two (29%) patients and 10,000
      100,000 copies/ml in three (43%) patients on last visit. No genotypic resistance
      to adefovir was detected. Lamivudine followed by adefovir salvage is effective
      for prophylaxis of recurrence of HBV after liver transplantation up to 7 years.

PMID- 19107975
TI  - Human herpesvirus 8 seroprevalence among Tobago women and the role of sexual
      lifestyle behavior.
AB  - Human herpesvirus 8 (HHV-8) infection is present in 22.9% of Tobago men. However,
      seroprevalence and modes of transmission of HHV-8 among Tobago women are not
      known. HHV-8 seropositivity rates in Tobago women were examined and compared
      rates to Tobago men of similar ages. To assess possible modes of transmission,
      sexual behavior among Tobago women was examined to determine its association with
      HHV-8 seropositivity. A cross-sectional study was conducted in 213 Tobago women,
      ages 18-65 years, who participated in the Tobago Cervical and Oral Cancer
      Screening Study. HHV-8 seropositivity was determined by a monoclonal
      immunofluorescence assay. Age-specific rates were compared to those previously
      observed in men. Logistic regression analyses were performed to determine the
      association between HHV-8 seropositivity and sexual behavior among the women. HHV
      8 seroprevalence among Tobago women was 14.1% (95% CI, 10-19%), with no
      significant difference with men of similar age (P-value = 0.741). Age <or=17
      years at first sexual intercourse was found to have a minimal significant
      association with HHV-8 seropositivity (OR = 2.51, 95% CI = 1.09-5.78) in women.
      HHV-8 age-specific rates were similar between genders. Sexual activity may not be
      a major contributor to HHV-8 infection among Tobago women.

PMID- 19107977
TI  - Molecular epidemiology of hepatitis C infection in Cyprus: evidence of
      polyphyletic infection.
AB  - The genetic diversity of the hepatitis C virus (HCV) in Cyprus is investigated
      for the first time in this study. Nucleotide sequence analysis of the CORE-E1 and
      NS5B regions of the HCV genome was performed on blood plasma samples obtained
      from 77 HCV patients in Cyprus, collected during 2005-2008. The amplified
      products were sequenced and compared to reference HCV strains of known genotype
      and subtype in order to classify the isolates found in this study. Genotype could
      be determined for all strains, and subtype for all but four isolates.
      Phylogenetic analysis revealed that 51 patients were genotype 1, of which 38 were
      subtype 1b, 9 were 1a, and 1 was unclassified, one patient was genotype 2c, 13
      were genotype 3a, nine were genotype 4, of which six were subtype 4a, and three
      were of unclassified subtype, one was genotype 5a, two patients seem to carry a
      possible 2k/1b recombinant strain, and no genotype 6 strains were found. This
      study demonstrated a genetic heterogeneity of HCV infection in Cyprus, with five
      of the six known HCV genotypes on the island, including unclassified isolates in
      genotypes 1 and 4, and also the apparent introduction of the 2k/1b recombinant
      strain in intravenous drug users.

PMID- 19107978
TI  - Prevalence of HHV-6 integrated chromosomally among children treated for acute
      lymphoblastic or myeloid leukemia in the Czech Republic.
AB  - Chromosomal integration of human herpesvirus 6 (HHV-6) is a novel situation found
      in a small percentage of individuals. While active HHV-6 infection is treatable
      using antivirals, the abnormally high level of HHV-6 DNA found in chromosomal
      integration of HHV-6 (CI-HHV-6) is not affected by such drugs. Stored DNA samples
      taken originally for detection of fusion genes and minimal residual disease from
      339 pediatric patients treated for leukemia in the Czech Republic between the
      years 1995-2007 were tested retrospectively. Using real-time quantitative PCR
      technology, the quantity of HHV-6 DNA detected was normalized to 100,000 human
      genome equivalents as assessed by quantitation of the albumin gene. HHV-6 DNA was
      detected in 107 samples from 91 patients (26.8%). In the majority of samples (99)
      only a minute level of normalized viral copies (NVCs) (median 1.84 NVCs) was
      detected. A high viral load of approximately 100,000 NVCs was detected in 5
      patients (1.5%; median 140,150 NVCs), in all of whom were confirmed subsequently
      CI-HHV-6 by a detection of HHV-6 DNA in hair follicles or in the nails. In all
      but one patient with HHV-6 variant B, variant A of the virus was detected. None
      of the patients with CI-HHV-6 had complications attributable to HHV-6 infection.
      The prevalence of CI-HHV-6 in childhood leukemia does not differ from that
      published for other patients or healthy populations. Where high levels of HHV-6
      DNA are present, CI-HHV-6 should be confirmed as soon as possible so that
      potentially toxic but ineffective antiviral treatment can be stopped.

PMID- 19107979
TI  - Seroepidemiology of EBV and interpretation of the "isolated VCA IgG" pattern.
AB  - The presence of VCA IgG in the absence of VCA IgM and EBNA-1 IgG antibodies makes
      classifying EBV infection more difficult as this serological picture can be seen
      in the case of past infection with EBNA-1 IgG loss or non-appearance, or acute
      infections with the early disappearance or delayed onset of VCA IgM. The aim of
      this study was to assess the prevalence of this pattern in 2,422 outpatients with
      suspected EBV infection examined in 2005-2006, and to interpret its significance
      by means of immunoblotting. One hundred and seventy-seven (7.3%) of the patients
      were VCA IgG-positive, VCA IgM-negative and EBNA-1 IgG-negative, 15 of whom
      (8.5%) presented with heterophile antibodies. Analysis by age class showed that
      the prevalence of isolated VCA IgG ranged from 4.5% in the subjects aged 1-10
      years to 9% in those aged >60 years. Immunoblotting allowed 18.9% of the cases to
      be classified as acute and 81.1% as past infections, the latter being observed in
      about 37% of the patients aged less than 10 years and in 100% of those aged >30
      years. Therefore, in our case series, the presence of isolated VCA IgG was
      associated usually with past infection, particularly among adults. In children
      aged less than 10 years, it was associated mainly with acute infection but as
      past infection may be present in about one-third of such children, this
      possibility should not be overlooked.

PMID- 19107980
TI  - Epidemiology of enterovirus types causing neurological disease in Austria 1999
      2007: detection of clusters of echovirus 30 and enterovirus 71 and analysis of
      prevalent genotypes.
AB  - Between 1999 and 2007 1,388 stool specimens from patients with acute flaccid
      paralysis or aseptic meningitis were submitted to the Austrian reference
      laboratory for poliomyelitis. Samples (201) yielded non-poliovirus enterovirus in
      culture. One hundred eighty-one viruses were available for typing and 78 isolates
      which remained serologically untyped were further analyzed by CODEHOP-PCR and
      sequencing of the VP1 gene and the 5'-untranslated region (5'-UTR). Typing
      revealed an Echovirus 30 outbreak in northwestern Austria in 2000, which was in
      accordance with the situation in Europe, and no dramatic seasonal changes of
      Coxsackie viruses were observed. In 2002/2003 a small outbreak of enterovirus 71
      (EV71), affected 12 patients in the province of Styria. This virus was identified
      as genotype C1 and appeared to be genetically distinct from the isolates observed
      in 2001/2002 in Vienna. In 2004 two unrelated cases occurred in Lower Austria,
      which were identified as genotype C4, which has been described associated with
      high mortality most recently in China. In contrast to the situation in Asia the
      detected EV71 cases were not associated with hand-foot-mouth disease, but with
      serous meningitis only. This was surprising as a recent publication suggested a
      reduced neurovirulence of C1 genotype in children in Norway, presumably due to
      alterations in 5'-UTR and polymerase gene. However, comparing the 5'-UTR of the
      Austrian isolates and established virulent reference strains to the Norwegian
      isolate and an attenuated EV71 laboratory strain we did not find an indication
      that the genotype C1 possesses a RNA structure in its 5'-UTR leading to reduced
      neurovirulence.

PMID- 19107981
TI  - Genetic diversity and zoonotic potential of human rotavirus strains, 2003-2006,
      Hungary.
AB  - Rotavirus strain surveillance is being conducted in many countries before and
      after introduction of newly licensed vaccines to assess the impact of the
      vaccines on rotavirus strains. Here we describe a strain surveillance study in
      the Budapest area of Hungary (2003-2006) based on RNA profile analysis,
      genotyping by multiplex PCR and nucleotide sequencing. Among 1,983 G-typed
      rotaviruses we identified G1 (22%), G2 (4.8%), G3 (3.5%), G4 (18.5%), G6 (1.1%),
      G8 (<0.1%, n = 1), G9 (42%), and G12 (3.4%) specificities. Information on P
      genotype incidence was determined for a subset of samples (n = 814). In addition
      to the globally important strains, a variety of uncommon antigen combinations
      were also found, for example, P[9],G3; P[14],G6; or P[14],G8. Sequence and
      phylogenetic analysis of the VP7, VP4, VP6, and NSP4 genes of selected strains
      with uncommon antigen combinations demonstrated high similarity with certain
      bovine, porcine, feline, equine, and lapine rotaviruses, respectively. Continued
      surveillance is needed to assess the role of animal rotaviruses in human
      diseases.

PMID- 19107982
TI  - In vitro analysis of synergism and antagonism of different nucleoside/nucleotide
      analogue combinations on the inhibition of human immunodeficiency virus type 1
      replication.
AB  - In this study we have developed an in vitro system to evaluate the combined
      effect of two NRTIs on HIV replication and to assess their antagonism or synergy.
      Synergy or antagonism effect was determined in peripheral blood mononuclear cells
      (PBMCs) to approach a more physiological model than T-cell lines. PBMCs were
      infected with a full-length HIV-1 clone carrying the luciferase gene as a
      reporter. The following combinations were investigated: zidovudine+stavudine (ZDV
      + d4T), lamivudine + abacavir (3TC + ABC), lamivudine + didanosine (3TC + ddI),
      lamivudine + stavudine (3TC + d4T), tenofovir + stavudine (TDF + d4T), tenofovir
      + didanosine (TDF + ddI), tenofovir + abacavir (TDF + ABC), tenofovir +
      lamivudine (TDF + 3TC), tenofovir + zidovudine (TDF + ZDV), stavudine +
      didanosine (d4T + ddI), zidovudine + lamivudine (ZDV + 3TC), abacavir +
      didanosine (ABC + ddI), zidovudine + didanosine (ZDV + ddI), and abacavir +
      stavudine (ABC + d4T). The effect of combining two drugs was evaluated with a
      quantitative method based on the median-effect principle of Chou and Talalay. A
      synergistic effect was observed with combinations containing TDF and ZDV or d4T,
      d4T and ddI and ZDV plus 3TC. In contrast, combinations including TDF + ddI, 3TC
      + ddI, ABC + ddI, and ZDV + ddI showed an antagonistic effect on the inhibition
      of viral replication at all levels of inhibition tested. Lower antagonistic
      effect was also found in drug combinations that included 3TC + ABC, 3TC + TDF,
      3TC + d4T, and TDF + ABC. In conclusion, the method developed allows to measure
      in vitro the effect of different combinations of two NRTIs on HIV replication.
      The results suggest that combined therapy including TDF with thymidine analogues
      may be considered for future therapeutic options in contrast to clearly
      antagonistic combinations such us TDF plus ddI or 3TC plus ddI, that would
      explain virological failure in clinical studies when these combinations were
      used.

PMID- 19107984
TI  - Patterns of care in elderly glioblastoma patients.
AB  - OBJECTIVE: To evaluate the patterns of care in elderly glioblastoma (GBM)
      patients from a large population-based registry. METHODS: We identified a cohort
      of GBM patients 65 years or older from Surveillance, Epidemiology, and End
      Results cancer registry data linked with Medicare claims between 1994 and 2002.
      We assessed the impact of demographic characteristics and comorbidities on the
      probability of undergoing surgical resection, radiotherapy (RT), and chemotherapy
      within 3 months of diagnosis using multivariate logistic regression. RESULTS: A
      total of 4,137 patients with GBM were included, with a median overall survival of
      4 months. Sixty-one percent of patients underwent resection at diagnosis; 65%
      received RT and 10% received chemotherapy within 3 months of diagnosis. In a
      multivariate regression analysis, age was the most significant predictor of
      resection, RT, or chemotherapy. Black race (odds ratio [OR], 0.64; p = 0.008) was
      associated with lower rates of surgical resection. Factors associated with
      decreased likelihood of receiving RT included unmarried marital status (OR, 0.64;
      p < 0.0001) and more comorbidities (OR, 0.55; p < 0.0001). Factors associated
      with decreased likelihood of receiving chemotherapy included unmarried marital
      status (OR, 0.59; p = 0.0002) and more comorbidities (OR, 0.56; p = 0.02).
      INTERPRETATION: Survival of elderly GBM patients was poor in this population
      based study. Age, marital status, and comorbidities influenced the probability of
      receiving RT or chemotherapy in this cohort.

PMID- 19107985
TI  - Senate probe seeks industry payment data on individual academic researchers.

PMID- 19107986
TI  - Quantitative magnetic resonance imaging analyses and clinical significance of
      hyperintense white matter lesions in systemic lupus erythematosus patients.
AB  - OBJECTIVE: To analyze the clinical significance of hyperintense white matter (WM)
      lesions in both symptomatic and asymptomatic systemic lupus erythematosus (SLE)
      patients. METHODS: We studied 120 consecutive SLE patients and 44 healthy
      volunteers. Fluid attenuated inversion recovery and T2-weighted magnetic
      resonance images (MRI) were used for visual and semiautomatic volumetric
      measurements. RESULTS: At baseline, 61 MRI were normal and 59 had hyperintense WM
      lesions. Mean volumes of WM lesions were 96.14 (SD = 85.14) mm(3) in T2 weighted
      and 197.2 (161.13) mm(3) in FLAIR images. The volume of WM lesions was associated
      with age (r = 0.45; p = 0.01), total corticosteroid dose (r = 0.53; p = 0.001),
      and Systemic Lupus International Collaborating Clinics/American College of
      Rheumatology Damage Index scores (r = 0.55; p = 0.002). After a median follow-up
      time of 24 months (SD = 2.3; range = 12-28 months), 20 patients had still normal
      MRIs, 30 patients had stable MRI findings, and 30 had new WM lesions. Predictors
      for new or increased WM lesions were past central nervous system manifestations
      (p = 0.001; OR = 12.2; 95% CI = 3.5-21.2), antiphospholipid antibodies (p =
      0.003; OR = 6.9; 95% CI = 2.1-15.3); Systemic Lupus International Collaborating
      Clinics/American College of Rheumatology Damage Index scores (p = 0.002; OR =
      7.2; 95% CI = 1.4-17.8) and higher dose of total corticosteroid dose (p = 0.01;
      OR = 2.4; 95% CI = 1.4-6.7). CONCLUSION: Small hyperintense WM lesions in SLE are
      associated with central nervous system symptoms and antiphospholipid antibodies,
      and progress over time in patients with more severe SLE. Therefore, in the
      context of SLE, these lesions are likely consequences of central nervous system
      damage and not mere incidental finding.

PMID- 19107987
TI  - Translational research for a new administration: what sort of change to believe
      in?

PMID- 19107988
TI  - Glucose and NADPH oxidase drive neuronal superoxide formation in stroke.
AB  - OBJECTIVE: Hyperglycemia has been recognized for decades to be an exacerbating
      factor in ischemic stroke, but the mechanism of this effect remains unresolved.
      Here, we evaluated superoxide production by neuronal nicotinamide adenine
      dinucleotide phosphate (NADPH) oxidase as a possible link between glucose
      metabolism and neuronal death in ischemia-reperfusion. METHODS: Superoxide
      production was measured by the ethidium method in cultured neurons treated with
      oxygen-glucose deprivation and in mice treated with forebrain ischemia
      reperfusion. The role of NADPH oxidase was examined using genetic disruption of
      its p47(phox) subunit and with the pharmacological inhibitor apocynin. RESULTS:
      In neuron cultures, postischemic superoxide production and cell death were
      completely prevented by removing glucose from the medium, by inactivating NADPH
      oxidase, or by inhibiting the hexose monophosphate shunt that generates NADPH
      from glucose. In murine stroke, neuronal superoxide production and death were
      decreased by the glucose antimetabolite 2-deoxyglucose and increased by high
      blood glucose concentrations. Inactivating NADPH oxidase with either apocynin or
      deletion of the p47(phox) subunit blocked neuronal superoxide production and
      negated the deleterious effects of hyperglycemia. INTERPRETATION: These findings
      identify glucose as the requisite electron donor for reperfusion-induced neuronal
      superoxide production and establish a previously unrecognized mechanism by which
      hyperglycemia can exacerbate ischemic brain injury.

PMID- 19107989
TI  - A critical role for Fas/CD-95 dependent signaling pathways in the pathogenesis of
      hyperoxia-induced brain injury.
AB  - OBJECTIVE: Prematurely born infants are at risk for development of neurocognitive
      impairment in later life. Oxygen treatment has been recently identified as a
      trigger of neuronal and oligodendrocyte apoptosis in the developing rodent brain.
      We investigated the role of the Fas death receptor pathway in oxygen-triggered
      developmental brain injury. METHODS: Six-day-old Wistar rats were exposed to 80%
      oxygen for various periods (2, 6, 12, 24, 48, and 72 hours), and mice deficient
      in either Fas (B6.MRL-Tnfrsf6(lpr)) or Fas ligand (B6Smn.C3-Fasl(gld)) and
      control mice (C57BL/6J) were exposed to 80% oxygen for 24 hours. Polymerase chain
      reaction, Western blotting, and caspase activity assays of thalamus and cortex
      tissue were performed. RESULTS: Fas and Fas ligand messenger RNA and protein were
      upregulated. Furthermore, hyperoxia resulted in induction of downstream signaling
      events of Fas, such as Fas-associated death domain (FADD), the long and short
      form of FADD-like interleukin-1beta-converting enzyme (FLICE) inhibitory protein
      (FLIP-L, FLIP-S), and cleavage of caspase-8 and caspase-3. Injection of a
      selective caspase-8 inhibitor (TRP801, 1mg/kg) at the beginning of hyperoxia
      blocked subsequent caspase-3 cleavage in this model. B6.MRL-Tnfrsf6(lpr) mice
      were protected against oxygen-mediated injury, confirming Fas involvement in
      hyperoxia-induced cell death. Mice deficient in Fas ligand did not differ from
      control animals in the amount of cell death. INTERPRETATION: We conclude that
      neonatal hyperoxia triggers Fas receptor and its downstream signaling events in a
      Fas ligand-independent fashion. Lack of functional Fas receptors and selective
      pharmacological inhibition of caspase-8 prevents activation of caspase-3 and
      provides significant neuroprotection.

PMID- 19107990
TI  - Seizures and reproductive function: insights from female rats with epilepsy.
AB  - OBJECTIVE: Chronic seizures in women can have adverse effects on reproductive
      function, such as polycystic ovarian syndrome, but it has been difficult to
      dissociate the effects of epilepsy from the role of antiepileptic drugs. To
      distinguish the effects of chronic seizures from medication, we used the
      laboratory rat, because an epileptic condition can be induced without concomitant
      anticonvulsant drug treatment. METHODS: Adult female rats were administered the
      chemoconvulsant pilocarpine to initiate status epilepticus, which was decreased
      in severity by the anticonvulsant diazepam. These rats developed spontaneous
      seizures in the ensuing weeks, and are therefore termed epileptic. Controls were
      saline-treated rats, or animals that were injected with pilocarpine but did not
      develop status epilepticus. Ovarian cyclicity and weight gain were evaluated for
      2 to 3 months. Serum hormone levels were assayed from trunk blood, which was
      collected at the time of death. Paraformaldehyde-fixed ovaries were evaluated
      quantitatively. RESULTS: Rats that had pilocarpine-induced seizures had an
      increased incidence of acyclicity by the end of the study, even if status
      epilepticus did not occur. Ovarian cysts and weight gain were significantly
      greater in epileptic than control rats, whether rats maintained cyclicity or not.
      Serum testosterone was increased in epileptic rats, but estradiol, progesterone,
      and prolactin were not. INTERPRETATIONS: The results suggest that an epileptic
      condition in the rat leads to increased body weight, cystic ovaries, and
      increased testosterone levels. Although caution is required when comparing female
      rats with women, the data suggest that recurrent seizures have adverse effects,
      independent of antiepileptic drugs.

PMID- 19107991
TI  - Fast activity at seizure onset is mediated by inhibitory circuits in the
      entorhinal cortex in vitro.
AB  - OBJECTIVE: Network mechanisms responsible for focal seizure initiation are still
      largely unknown. One of the prevalent seizure patterns observed during diagnostic
      intracranial recordings performed in patients with mesial temporal lobe epilepsy
      is characterized by fast activity at 20 to 30 Hz. We reproduced 20 to 30 Hz
      oscillations at seizure onset in the temporal lobe of the in vitro isolated
      guinea pig brain to study cellular and network mechanisms involved in its
      generation. METHODS: Seizure-like activity was induced in the isolated brain by 3
      minute arterial perfusion of 50 microM bicuculline. Intracellular, extracellular,
      and ion-selective electrophysiological recordings were performed simultaneously
      in the entorhinal cortex (EC) during interictal-ictal transition. RESULTS:
      Principal neurons in deep and superficial layers of the EC did not generate
      action potentials during fast activity at ictal onset, whereas sustained firing
      was observed in putative interneurons. Within 5 to 10 seconds from seizure
      initiation, principal neurons generated a prominent firing that correlated with
      the appearance of extracellular hypersynchronous bursting discharges. In
      superficial neurons, fast activity correlated with rhythmic IPSPs that
      progressively decreased in amplitude during the development of a slow
      depolarization associated with an increase in extracellular potassium.
      INTERPRETATION: We conclude that in an acute model of temporal lobe ictogenesis,
      sustained inhibition without firing of EC principal neurons correlates with the
      onset of a focal seizure. The progression of the ictal discharge is contributed
      by a potassium-dependent change in reversal potential of inhibitory postsynaptic
      potentials. These findings demonstrate a prominent role of inhibitory networks
      during the transition to seizure in the EC.

PMID- 19107992
TI  - Multiple sodium channel isoforms and mitogen-activated protein kinases are
      present in painful human neuromas.
AB  - OBJECTIVE: Although axons within neuromas have been shown to produce
      inappropriate spontaneous ectopic discharges, the molecular basis for pain in
      patients with neuromas is still not fully understood. Because sodium channels are
      known to play critical roles in neuronal electrogenesis and hyperexcitability, we
      examined the expression of all the neuronal voltage-gated sodium channels
      (Nav1.1, Nav1.2, Nav1.3, Nav1.6, Nav1.7, Nav1.8, and Nav1.9) within human painful
      neuromas. We also examined the expression of two mitogen-activated protein (MAP)
      kinases, activated p38 and extracellular signal-regulated kinases 1 and 2
      (ERK1/2), which are known to contribute to chronic pain, within these human
      neuromas. METHODS: We used immunocytochemical methods with specific antibodies to
      sodium channels Nav1.1, Nav1.2, Nav1.3, Nav1.6, Nav1.7, Nav1.8, and Nav1.9, and
      to activated MAP kinases p38 and ERK1/2 to study by confocal microscopy control
      and painful neuroma tissue from five patients with well-documented pain. RESULTS:
      We demonstrate upregulation of sodium channel Nav1.3, as well as Nav1.7 and
      Nav1.8, in blind-ending axons within human painful neuromas. We also demonstrate
      upregulation of activated p38 and ERK1/2 MAP kinases in axons within these
      neuromas. INTERPRETATION: These results demonstrate that multiple sodium channel
      isoforms (Nav1.3, Nav1.7, and Nav1.8), as well as activated p38 and ERK1/2 MAP
      kinases, are expressed in painful human neuromas, indicating that these molecules
      merit study as possible therapeutic targets for the treatment of pain associated
      with traumatic neuromas.

PMID- 19107994
TI  - Glioblastoma in the elderly: an age-old problem.

PMID- 19107993
TI  - The brain in the age of old: the hippocampal formation is targeted differentially
      by diseases of late life.
AB  - OBJECTIVE: To rely on the anatomical organization of the hippocampal formation in
      understanding whether and how late-life diseases such as diabetes and stroke
      contribute to age-related cognitive decline. METHODS: Magnetic resonance imaging
      (MRI) was used to document brain infarcts and to generate high-resolution
      functional maps of the hippocampal formation in 240 community-based nondemented
      elders (mean age, 79.7 years) who received a comprehensive medical evaluation.
      Sixty participants had type 2 diabetes mellitus, whereas 74 had MRI-documented
      brain infarcts, and the first analysis was designed to pinpoint hippocampal
      subregions differentially linked to each disorder. Then, guided by the results,
      additional functional MRI studies in aging rhesus monkeys and mice were used to
      test proposed mechanisms of dysfunction. RESULTS: Although both diabetes and
      brain infarcts were associated with hippocampal dysfunction, each was linked to
      separate hippocampal subregions, suggesting distinct underlying mechanisms. The
      hippocampal subregion linked to diabetes implicated blood glucose as a pathogenic
      mechanism, a hypothesis confirmed by imaging aging rhesus monkeys and a mouse
      model of diabetes. The hippocampal subregion linked to infarcts suggested
      transient hypoperfusion as a pathogenic mechanism, a hypothesis provisionally
      confirmed by comparing anatomical patterns across subjects with infarcts in
      different vascular territories. INTERPRETATION: Taken together with previous
      findings, these results clarify how diseases of late life differentially target
      the hippocampal formation, identify elevations in blood glucose as a contributing
      cause of age-related memory decline, and suggest specific interventions that can
      preserve cognitive health.

PMID- 19107995
TI  - Quantitative neuroimaging advances in the measurement of brain injury but not
      brain function in systemic lupus erythematosus.

PMID- 19107996
TI  - Neurological disease on the global agenda.

PMID- 19107997
TI  - Alzheimer's disease and anesthesia: out of body, out of mind...or not?

PMID- 19107998
TI  - Quantitative in vivo magnetic resonance imaging of multiple sclerosis at 7 Tesla
      with sensitivity to iron.
AB  - OBJECTIVE: Magnetic resonance imaging at 7 Tesla produces high-resolution
      gradient-echo phase images of patients with multiple sclerosis (MS) that quantify
      the local field shifts from iron in the basal ganglia and lesions. Phase imaging
      is easily integrated into clinical examinations because it is a postprocessing
      technique and does not require additional scanning. The purpose of this study was
      to quantify local field shifts in MS and to investigate their relation to disease
      duration and disability status. METHODS: Thirty-two subjects including 19
      patients with MS and 13 age- and sex-matched control subjects were scanned at a
      spatial resolution of up to 195 x 260 microm. Data were postprocessed to produce
      anatomical quantitative phase images of local field shifts, as well as
      conventional magnitude images. RESULTS: The phase images showed an increased
      local field in the caudate, putamen, and globus pallidus of patients relative to
      control subjects (p < 0.01). The local field in the caudate was strongly
      correlated with disease duration (r(2) = 0.77; p < 0.001). Phase images showed
      contrast in 74% of the 403 lesions, increasing the total lesion count by more
      than 30% and showing distinct peripheral rings and a close association with
      vasculature. INTERPRETATION: The increased field in the basal ganglia and
      correlation with disease duration suggest pathological iron content increases in
      MS. The peripheral phase rings are consistent with histological data
      demonstrating iron-rich macrophages at the periphery of a subset of lesions. The
      clearly defined vessels penetrating MS lesions should increase our ability to
      detect focal vascular abnormalities specifically related to demyelinating
      processes.

PMID- 19107999
TI  - Epigenetics and the nervous system.
AB  - We are in the midst of a revolution in the genomic sciences that will forever
      change the way we view biology and medicine, particularly with respect to brain
      form, function, development, evolution, plasticity, neurological disease
      pathogenesis and neural regenerative potential. The application of epigenetic
      principles has already begun to identify and characterize previously unrecognized
      molecular signatures of disease latency, onset and progression, mechanisms
      underlying disease pathogenesis, and responses to new and evolving therapeutic
      modalities. Moreover, epigenomic medicine promises to usher in a new era of
      neurological therapeutics designed to promote disease prevention and recovery of
      seemingly lost neurological function via reprogramming of stem cells, redirecting
      cell fate decisions and dynamically modulating neural network plasticity and
      connectivity.

PMID- 19108001
TI  - Randomized clinical trial comparing decellularized bovine ureter with expanded
      polytetrafluoroethylene for vascular access.
AB  - BACKGROUND: The SynerGraft model 100 (SG 100) is a decellularized bovine uereter
      graft developed to improve on prosthetic conduits for vascular access. Its
      clinical performance was compared with polytetrafluoroethylene (ePTFE) in a
      prospective, pilot randomized study. METHODS: Patients requiring haemodialysis
      with no native vein options were included. Between June 2004 and June 2007, 29
      patients received SG 100 and 27 ePTFE grafts. Forty-five patients had undergone
      previous access surgery. All grafts were between the brachial artery and the
      axillary vein. RESULTS: Clinical details were similar between the groups; overall
      mean(s.d.) follow-up was 469(398) days. After 1 year, there were no significant
      differences in primary patency (28 per cent for SG 100 versus 48 per cent for
      ePTFE; P = 0.290), assisted primary patency (52 versus 64 per cent; P = 0.430) or
      secondary patency (57 versus 68 per cent; P = 0.370). Freedom from infection at 1
      year was 96 per cent for SG 100 and 91 per cent for ePTFE (P = 0.410). Fifty
      seven further procedures (18 endovascular and 39 surgical) were needed to
      maintain patency in 50 grafts (23 SG 100 and 27 ePTFE). CONCLUSION: Both grafts
      were adequate conduits for haemodialysis and were amenable to repair. Anticipated
      advantages for SG 100 were not seen in either patency or stability.

PMID- 19108000
TI  - Effect of structural parameters of peptides on dimer formation and highly
      oxidized side products in the oxidation of thiols of linear analogues of human
      beta-defensin 3 by DMSO.
AB  - The purpose of this study was to examine the effects of structural parameters of
      peptides on their oxidation by DMSO, including location of cysteine, effect of
      adjunct group participation, molecular hydrophobicity, steric hindrance or the
      accessibility of thiol group and peptide conformation, on oxidation rates, dimer
      formation and associated side products. We designed and synthesized two series of
      linear cysteine-containing analogues of human beta-defensin 3 (the C1-peptides
      with cysteine at the N-terminus residue 1, the C29-peptides with cysteine located
      at residue 29 in the centre of peptide), which were used for preparation of
      disulphide-linked homodimers. HPLC-ESI-MS was used to monitor the oxidation
      process and to characterize the molecular weights of dimers and side products of
      high oxidation. The formations of dimers and side products were dependent on the
      position of cysteines. Hydrophobicity generally rendered the thiol groups less
      accessible and hence exposed them to slow oxidation to form dimers (or even fail
      to form dimers during the timescale of observation). Molecular dynamics
      simulations showed that the exposure of cysteines (and sulphurs) of the C1
      peptides was much larger than for the C29-peptides. The larger hydrophobic side
      chains tended to enable clustering of the side chains that sequester cysteine,
      particularly in the C29-peptides, which provided a molecular explanation for the
      observed trends in oxidation rates. Together with molecular modelling, we propose
      a reaction mechanism to elucidate the oxidation results of these peptides.

PMID- 19108002
TI  - Impact on regional recurrence and survival of axillary surgery in women with node
      negative primary breast cancer.
AB  - BACKGROUND: This study examined whether axillary lymph node dissection (ALND)
      with removal of many normal lymph nodes resulted in a reduced rate of axillary
      recurrence and better survival, as reported in recent studies. METHODS: The
      follow-up analyses were based on 8657 patients with node-negative primary breast
      cancer treated solely by surgery. Median follow-up was 9 years. RESULTS: The
      number of lymph nodes removed correlated with a reduction in the rate of
      subsequent axillary recurrence (from 2.1 to 0.4 per cent; P = 0.037), local
      recurrence (from 7.4 to 3.8 per cent; P < 0.001) distant metastases (from 15.0 to
      10.3 per cent; P < 0.001) and death as first event (from 7.5 to 5.5 per cent; P =
      0.012). CONCLUSION: When ALND is indicated, at least ten axillary lymph nodes
      should be retrieved. The role of ALND as primary treatment has decreased
      significantly during the past decade. The findings leave the concept of the
      sentinel node biopsy intact, as a highly specific procedure compared to ALND.

PMID- 19108003
TI  - Importance of routine cavity sampling in breast conservation surgery.
AB  - BACKGROUND: The role of cavity biopsy (CB) at the time of wide local excision
      (WLE) for primary breast cancer has not been evaluated fully. This study compared
      four groups of patients to determine the significance of margins and CB histology
      on tumour characteristics and outcome. METHODS: This was a retrospective study of
      patients undergoing WLE and CB in one institution over 21 years. Demographic
      data, tumour characteristics and survival information were obtained. Four
      subgroups of patients were compared according to their margin and cavity status
      (positive or negative). RESULTS: A total of 957 patients had WLE. The median 10
      year survival was 85.6 per cent and breast cancer-specific survival was 92.4 per
      cent. Tumour size, grade, node and oestrogen receptor status were independent
      predictors of survival. There was poor concordance between positivity of
      resection margins and CB (32.0 per cent); a negative margin carried a 10.8 per
      cent risk of demonstrable residual disease. A positive CB, but not a positive
      margin, was associated with reduced overall survival and breast cancer-specific
      survival. CONCLUSION: Cavity status was more significant with regard to survival
      than margin status. CB is important in identifying residual and multifocal
      disease, as margin and cavity positivity are often not concordant.

PMID- 19108004
TI  - In memoriam: Dr. Herbert Falk (1924-2008).

PMID- 19108005
TI  - Therapy for portal hypertension: What is our pipeline?

PMID- 19108006
TI  - Non-invasive ventilation for treatment of postoperative respiratory failure after
      oesophagectomy.
AB  - BACKGROUND: The aim of this case-control study was to compare the efficacy of non
      invasive positive pressure ventilation (NPPV) with that of conventional treatment
      in patients who develop postoperative acute respiratory failure (ARF) after
      oesophagectomy. METHODS: Thirty-six consecutive patients with ARF treated by NPPV
      were matched for diagnosis, age within 5 years, sex, preoperative
      radiochemotherapy and Charlson co-morbidity index with 36 patients who received
      conventional treatment (control group). RESULTS: NPPV was associated with a lower
      reintubation rate (nine versus 23 patients; P = 0.008), lower frequency of acute
      respiratory distress syndrome (eight versus 19 patients; P = 0.015), and a
      reduction in intensive care stay (mean(s.d.) 14(13) versus 22(18) days; P =
      0.034). Anastomotic leakage was less common in patients receiving NPPV (two
      versus ten; P = 0.027). These patients also showed a greater improvement in gas
      exchange in the first 3 days after onset of ARF (P = 0.013). CONCLUSION: The use
      of NPPV for the treatment of postoperative ARF may decrease the incidence of
      endotracheal intubation and related complications, without increasing the risk of
      anastomotic leakage after oesophagectomy.

PMID- 19108007
TI  - Advanced technologies and the future of medicine and surgery.
AB  - Technology has become a major driver of the future direction of healthcare and
      surgery. Likewise, the speed of change has accelerated beyond comprehension, with
      a number of revolutions occurring during a surgeon's career. Being an agent of
      change or rapidly adapting to change has become the hallmark of the gifted
      surgeon. The fundamental challenges to a future surgeon are addressed from a
      technological viewpoint, with emphasis on the impact upon healthcare.

PMID- 19108008
TI  - Robotic surgery for cervical cancer.
AB  - The development of robotic technology has facilitated the application of
      minimally invasive techniques for the treatment and evaluation of patients with
      early, advanced, and recurrent cervical cancer. The application of robotic
      technology for selected patients with cervical cancer and the data available in
      the literature are addressed in the present review paper. The robotic radical
      hysterectomy technique developed at the Mayo Clinic Arizona is presented with
      data comparing 27 patients who underwent the robotic procedure with 2 matched
      groups of patients treated by laparoscopic (N = 31), and laparotomic radical
      hysterectomy (N = 35). A few other studies confirmed the feasibility and safety
      of robotic radical hysterectomy and comparisons to either to the laparoscopic or
      open approach were discussed. Based on data from the literature, minimally
      invasive techniques including laparoscopy and robotics are preferable to
      laparotomy for patients requiring radical hysterectomy, with some advantages
      noted for robotics over laparoscopy. A prospective randomised trial is currently
      being performed under the auspices of the American Association of Gyneoclogic
      Laparoscopists comparing minimally invasive radical hysterectomy (laparoscopy or
      robotics) with laparotomy. For early cervical cancer radical parametrectomy and
      fertility preserving trachelectomy have been performed using robotic technology
      and been shown to be feasible, safe, and easier to perform when compared to the
      laparoscopic approach. Similar benefits have been noted in the treatment of
      advanced and recurrent cervical cancer where complex procedures such as
      extraperitoneal paraortic lymphadenectomy and pelvic exenteration have been
      required. CONCLUSION: Robotic technology better facilitates the surgical approach
      as compared to laparoscopy for technically challenging operations performed to
      treat primary, early or advanced, and recurrent cervical cancer. Although patient
      advantages are similar or slightly improved with robotics, there are multiple
      advantages for surgeons.

PMID- 19108009
TI  - Robotic surgery in gynecologic field.
AB  - Operative laparoscopy was initially developed in the field of gynecology earlier
      on and the advent of laparoscopic surgery led to advances in general surgery as
      well. In the last few years, a number of articles have been published on the
      performance of surgical procedures using the robot-assisted laparoscopy. The
      shortcomings of conventional laparoscopy have led to the development of robotic
      surgical system and future of telerobotic surgery is not far away, enabling a
      surgeon to operate at a distance from the operating table. The complete loss of
      tactile sensation is often quoted as a big disadvantage of working with robotic
      systems. Although the first generation da Vinci robotic surgical system provides
      improved imaging and instrumentation, the absence of tactile feedback and the
      high cost of the technology remain as limitations. New generations of the robotic
      surgical systems have been developed, allowing visualization of preoperative
      imaging during the operation. Though the introduction of robotics is very recent,
      the potential for robotics in several specialties is significant. However, the
      benefit to patients must be carefully evaluated and proven before this technology
      can become widely accepted in the gynecologic surgery.

PMID- 19108010
TI  - Robotic colorectal surgery.
AB  - Robotic colorectal surgery has gradually been performed more with the help of the
      technological advantages of the da Vinci system. Advanced technological
      advantages of the da Vinci system compared with standard laparoscopic colorectal
      surgery have been reported. These are a stable camera platform, three-dimensional
      imaging, excellent ergonomics, tremor elimination, ambidextrous capability,
      motion scaling, and instruments with multiple degrees of freedom. However,
      despite these technological advantages, most studies did not report the clinical
      advantages of robotic colorectal surgery compared to standard laparoscopic
      colorectal surgery. Only one study recently implies the real benefits of robotic
      rectal cancer surgery. The purpose of this review article is to outline the early
      concerns of robotic colorectal surgery using the da Vinci system, to present
      early clinical outcomes from the most current series, and to discuss not only the
      safety and the feasibility but also the real benefits of robotic colorectal
      surgery. Moreover, this article will comment on the possible future clinical
      advantages and limitations of the da Vinci system in robotic colorectal surgery.

PMID- 19108011
TI  - Yonsei experience in robotic urologic surgery-application in various urological
      procedures.
AB  - PURPOSE: The da Vinci robot system has been used to perform complex
      reconstructive procedures in a minimally invasive fashion. Robot-assisted
      laparoscopic radical prostatectomy has recently established as one of the
      standard cares. Based on experience with the robotic prostatectomy, its use is
      naturally expanding into other urologic surgeries. We examine our practical
      pattern and application of da Vinci robot system in urologic field. PATIENTS AND
      METHODS: Robotic urologic surgery has been performed during a period from July
      2005 to August 2008 in a total of 708 cases. Surgery was performed by 7
      operators. In our series, radical prostatectomy was performed in 623 cases,
      partial nephrectomy in 43 cases, radical cystectomy in 11 cases,
      nephroureterectomy in 18 cases and other surgeries in 15 cases. RESULTS: In the
      first year, robotic urologic surgery was performed in 43 cases. However, in the
      second year, it was performed in 164 cases, and it was performed in 407 cases in
      the third year. In the first year, only prostatectomy was performed. In the
      second year, partial nephrectomy (2 cases), nephroureterectomy (3 cases) and
      cystectomy (1 case) were performed. In the third year, other urologic surgeries
      than prostatectomy were performed in 64 cases. The first robotic surgery was
      performed with long operative time. For instance, the operative time of
      prostatectomy, partial nephrectomy, cystectomy and nephroureterectomy was 418,
      222, 340 and 320 minutes, respectively. Overall, the mean operative time of
      prostatectomy, partial nephrectomy, cystectomy and nephrourectectomy was 179,
      173, 309, and 206 minutes, respectively. CONCLUSION: Based on our experience at a
      single-institution, robot system can be used both safely and efficiently in many
      areas of urologic surgeries including prostatectomy. Once this system is familiar
      to surgeons, it will be used in a wide range of urologic surgery.

PMID- 19108012
TI  - Short insulin tolerance test can determine the effects of thiazolidinediones
      treatment in type 2 diabetes.
AB  - PURPOSE: The short insulin tolerance test is a simple and reliable method of
      estimating insulin sensitivity. This study was designed to compare the insulin
      sensitizing effects of thiazolidinediones (TZDs) on the degree of insulin
      resistance, determined by a short insulin tolerance test (Kitt) in type 2
      diabetic patients. PATIENTS AND METHODS: Eighty-three subjects (mean age = 57.87
      +/- 10.78) with type 2 diabetes mellitus were enrolled and received daily one
      dose of rosiglitazone (4 mg) or pioglitazone (15 mg). The mean follow-up duration
      was 25.39 +/- 9.66 months. We assessed insulin sensitivity using HOMA-IR and the
      short insulin tolerance test before and after TZDs treatment. RESULTS: When we
      compared patients' characteristics before and after TZDs treatment, the mean
      fasting glucose level was significantly decreased (183.27 +/- 55.04 to 137.35 +/-
      36.42 mg/dL, p < 0.001) and the mean HbA1C level was significantly decreased
      (9.24 +/- 1.96 to 8.11 +/- 1.39%, p < 0.001). Also, Kitt values were
      significantly increased (2.03 +/- 1.14 to 2.67 +/- 0.97%/min, p = 0.003), whereas
      HOMA-IR was significantly decreased (2.98 +/- 0.68 to 1.04 +/- 0.24, p < 0.05).
      When classifying insulin resistance by Kitt values, insulin resistant subjects'
      values were increased (< 2.5%/min; 1.51 +/- 0.53%/min to 2.63 +/- 0.88, p <
      0.001), whereas the values decreased in insulin sensitive subjects (>or=
      2.5%/min; 3.50 +/- 0.75%/min to 2.75 +/- 1.12%/min, p = 0.002). CONCLUSION: The
      glucose lowering effects of TZDs by improving insulin resistance could be
      determined by using Kitt. However, Kitt may be a beneficial tool to determine
      TZDs' effects only when patients' Kitt values are less than 2.5%/min.

PMID- 19108014
TI  - Decreased expression of 15-hydroxyprostaglandin dehydrogenase in gastric
      carcinomas.
AB  - PURPOSE: Gastric carcinoma tissues release high level of prostaglandin E2 (PGE2)
      when compared to non-neoplastic mucosa, and cyclooxygenase-2 (COX-2), which is
      the rate-limiting enzyme in prostaglandin (PG) biosynthesis, is often
      overexpressed in gastric carcinomas and during gastric carcinogenesis. However,
      little is known about the expression of 15-hydroxyprostaglandin dehydrogenase (15
      PGDH), the key enzyme responsible for the biological inactivation of PG, in
      gastric carcinomas. MATERIALS AND METHODS: We investigated the expression of 15
      PGDH in 28 cases of advanced gastric carcinomas by Western blot analysis and also
      the relation between its expression and the gene promoter methylation. RESULTS:
      15-PGDH expression was significantly decreased in gastric carcinomas compared to
      corresponding non-neoplastic tissues and inversely correlated with the expression
      of proliferating cell nuclear antigen in gastric carcinomas. However, there was
      no correlation between 15-PGDH expression and pathological findings such as nodal
      metastasis and vascular invasion. Promoter hypermethylation of 15-PGDH gene was
      not detected in carcinomas, with only a negligible expression of the enzyme.
      CONCLUSION: Our results suggested that 15-PGDH has tumor suppressor activity in
      gastric carcinomas.

PMID- 19108013
TI  - Reliability and validity of the Korean version of Obsessive-Compulsive Inventory
      Revised in a non-clinical sample.
AB  - PURPOSE: The reliability and validity of a Korean version of the Obsessive
      Compulsive-Inventory-Revised (OCI-R) was examined in non-clinical student
      samples. MATERIALS AND METHODS: The Korean version of OCI-R was administered to a
      total of 228 Korean college students. The Maudsley Obsessive Compulsive Inventory
      (MOCI), Beck's Depression Inventory (BDI), and Beck's Anxiety Inventory (BAI)
      were administered to 228 students. RESULTS: The total and each of subscale of the
      Korean OCI-R demonstrated excellent internal consistency, good test-retest
      reliability, moderate convergent validity and good divergent validity.
      CONCLUSION: It was concluded that the Korean version of the OCI-R has strong
      psychometric properties as the original version.

PMID- 19108015
TI  - Isotype and IgG subclass distribution of autoantibody response to alpha-enolase
      protein in adult patients with severe asthma.
AB  - PURPOSE: A possible involvement of autoimmune mechanism in the pathogenesis of
      bronchial asthma has been proposed. Recently, alpha-enolase protein was
      identified as a major autoantigen recognized by circulating IgG autoantibodies in
      patients with severe asthma. To evaluate a possible pathogenetic significance of
      these autoantibodies in severe asthma, isotype (IgG, IgA, IgM, and IgE) and IgG
      subclass (IgG1, IgG2, IgG3, and IgG4) distributions of autoantibodies to
      recombinant human alpha-enolase protein were analyzed. PATIENTS AND METHODS: We
      examined serum samples from 10 patients with severe asthma and 7 patients with
      mild-to-moderate asthma, and 5 healthy controls by immunoblot analysis. Severe
      asthma was defined as patients having at least 1 severe asthmatic exacerbation
      requiring an emergency department visit or admission in the last year despite
      continuous typical therapies. RESULTS: IgG1 was the predominant IgG subclass
      antibody response to alpha-enolase protein in patients with severe asthma. IgG1
      autoantibody to alpha-enolase protein was detected in 7 of 10 patients with
      severe asthma (70%), 1 of 7 patients with mild-to-moderate asthma (14.3%), and
      none of 5 healthy controls (0%) (chi-square test; p < 0.05). IgA, IgM, and IgE
      autoantibodies to alpha-enolase protein could not be detected in patients with
      severe asthma. CONCLUSION: IgG1 subclass was the predominant type of autoantibody
      response to alpha-enolase protein in patients with severe asthma, suggests a
      possibility of IgG1 autoantibody-mediated complement activation in the
      pathogenesis of severe asthma.

PMID- 19108016
TI  - Estimated prevalence and risk factor for age-related maculopathy.
AB  - PURPOSE: To assess the estimate prevalence and risk factors for age-related
      maculopathy (ARM) in Seoul, Korea. PATIENTS AND METHODS: We examined 9,530
      subjects with, 40 years of age or older between January 2006 and December 2006 in
      Seoul, Korea. Subjects underwent fundus photography, clinical examinations
      (including blood analyses), and completed detailed questionnaires. Fundus images
      were graded according to definitions from the Wisconsin Age-Related Maculopathy
      Grading System. RESULTS: ARM was present in 235 subjects, corresponding to an
      estimate prevalence of 2.46%. Hepatitis B infection (positive status for HBsAg
      and HBcAb), serum triglyceride levels and high density lipoprotein levels
      remained as significant risk factors after age-adjustment. Multivariate analyses
      showed that the prevalence of ARM was significantly higher in older subjects
      [odds ratio (OR) 1.134; 95% CI 1.114-1.154] and those who were seropositive for
      hepatitis B surface antigen (OR 2.566; 95% CI 1.519-4.335). CONCLUSION: The
      estimated prevalence of ARM was 2.46%. Age and hepatitis B infection may increase
      the risk of ARM.

PMID- 19108017
TI  - Prevalence of Foxp3 positive T regulatory cells is increased during progression
      of cutaneous squamous tumors.
AB  - PURPOSE: Forkhead box p3 (Foxp3) positive T regulatory cells (Tregs) have a
      functionally immunosuppressive property that prevents effector cells from acting
      against self in autoimmune diseases or a tumor. It is known that Tregs may be
      highly relevant in cancer progression. Dendritic cells (DCs) induce cutaneous
      immune response, however several studies have suggested that DCs are involved in
      immunosuppression. The aim of this study is to evaluate the prevalence of Tregs
      and DCs infiltration in cutaneous premalignant and malignant squamous lesions.
      MATERIALS AND METHODS: We evaluated Tregs and DCs in skin tissue samples obtained
      from 83 patients with actinic keratosis, Bowen's disease or squamous cell
      carcinoma by immunohistochemistry. RESULTS: The prevalence of Tregs and DCs was
      significantly higher in squamous cell carcinoma and Bowen's disease than in
      actinic keratosis. In addition, the number of DCs was closely correlated with the
      prevalence of Tregs, and DCs were also located in direct proximity to Tregs.
      CONCLUSION: Tregs is related to cutaneous squamous tumor progression.

PMID- 19108018
TI  - DNA gains and losses of chromosome in laryngeal squamous cell carcinoma using
      comparative genomic hybridization.
AB  - PURPOSE: A larynx squamous cell carcinoma (LSCC) is one of the most common forms
      of cancer and may exhibit various complex karyotypes. MATERIALS AND METHODS: We
      used comparative genomic hybridization (CGH) to analyze DNA gains and losses in
      15 squamous cell carcinomas that consisted of 4 glottic, 10 supraglottic, and 1
      transglottic localization samples. RESULTS: The majority of the chromosomal
      alterations detected were gains: 3 samples of LSCCs revealed high level
      amplification, while 6 samples displayed gains in various chromosomal regions
      (17p, 3p, 4p, 5p, 6q, 8p, 9p, 14q, 18p and Xq). One sample was found to have
      losses (chromosomes 15q and 22q) and 5 had normal CGH profiles. CONCLUSION: Many
      of these gained regions (4p, 5p, 8p, 10q, 18q and Xq) were novel sites, which may
      harbor oncogene(s) that potentially play an important role in squamous cell
      tumorigenesis and progression at supraglottic localizations.

PMID- 19108019
TI  - Comparison of combination posterior sub-tenon triamcinolone and modified grid
      laser treatment with intravitreal triamcinolone treatment in patients with
      diffuse diabetic macular edema.
AB  - PURPOSE: To compare the efficacy of posterior sub-Tenon's capsule triamcinolone
      acetonide injection combined with modified grid macular photocoagulation (PSTI +
      MP) with intravitreal triamcinolone acetonide (IVTA) injection in the treatment
      of diffuse diabetic macular edema (DME). MATERIALS AND METHODS: Forty eyes of 33
      patients with diffuse DME were randomly allocated into either PSTI + MP (20 eyes)
      or IVTA (20 eyes). Best corrected visual acuity (VA) and foveal thickness were
      measured. RESULTS: The ETDRS scores at baseline were 25.2 +/- 13.6 (mean +/- SD)
      letters in the PSTI + MP group, whereas 21.7 +/- 16.3 letters in the IVTA group.
      The ETDRS scores improved by 33.2 +/- 15.9, 34.7 +/- 16.6 and 30.9 +/- 19.0
      letters in the PSTI + MP group whereas by 30.9 +/- 15.4, 30.1 +/- 17.9 and 31.5
      +/- 15.0 letters in the IVTA group at 1, 3, and 6 months after the treatments,
      respectively. The VA improved significantly at 1 month and 3 months after both
      treatments (all p < 0.02, paired t-test). The VA improvements were no longer
      significant at 6 months in either group. There were no statistically significant
      differences at any time points between the 2 groups (all p > 0.05, Student's t
      test). The foveal thicknesses at baseline and 1, 3, and 6 months after the
      treatments were 382.8 +/- 148.3, 309.1 +/- 131.3, 319.3 +/- 93.3, 340.4 +/- 123.5
      microm (mean +/- SD) in the PSTI + MP group vs. 369.1 +/- 123.1, 241.4 +/- 52.3,
      277.5 +/- 137.4, 290.2 +/- 127.9microm in the IVTA group, respectively. Pairwise
      comparisons revealed significant decrease in foveal thickness at 1 month (p =
      0.01, paired t-test) for the PSTI + MP group, and at both 1 month (p < 0.001) and
      3 months (p = 0.016) for the IVTA group. There were no statistically significant
      differences at any time points between the 2 groups (all p > 0.05, Student's t
      test). In contrast to the PSTI + MP group, where no complications were noted, the
      elevation of intra-ocular pressure in 3 of 20 eyes (15%) and a significant
      increase in average cataract grading were observed in the IVTA group. CONCLUSION:
      PSTI + MP treatment provides significant improvement of vision in patients with
      diffuse DME over 3 months, and achieves outcomes comparable to those after IVTA
      treatment, however, with fewer complications.

PMID- 19108020
TI  - Point mutation of Hoxd12 in mice.
AB  - PURPOSE: Genes of the HoxD cluster play a major role in vertebrate limb
      development, and changes that modify the Hoxd12 locus affect other genes also,
      suggesting that HoxD function is coordinated by a control mechanism involving
      multiple genes during limb morphogenesis. In this study, mutant phenotypes were
      produced by treatment of mice with a chemical mutagen, N-ethyl-N-nitrosourea
      (ENU). We analyzed mutant mice exhibiting the specific microdactyly phenotype and
      examined the genes affected. MATERIALS AND METHODS: We focused on phenotype
      characteristics including size, bone formation, and digit morphology of ENU
      induced microdactyly mice. The expressions of several molecules were analyzed by
      genome-wide screening and quantitative real-time PCR to define the affected
      genes. RESULTS: We report on limb phenotypes of an ENU-induced A-to-C mutation in
      the Hoxd12 gene, resulting in alanine-to-serine conversion. Microdactyly mice
      exhibited growth defects in the zeugopod and autopod, shortening of digits, a
      missing tip of digit I, limb growth affected, and dramatic increases in the
      expressions of Fgf4 and Lmx1b. However, the expression level of Shh was not
      changed in Hoxd12 point mutated mice. CONCLUSION: These results suggest that
      point mutation rather than the entire deletion of Hoxd12, such as in knockout and
      transgenic mice, causes the abnormal limb phenotype in microdactyly mice. The
      precise nature of the spectrum of differences requires further investigation.

PMID- 19108021
TI  - Open pulmonary thromboembolectomy in patients with major pulmonary
      thromboembolism.
AB  - PURPOSE: We retrospectively analyzed open pulmonary thromboembolectomy in
      patients with acute and chronic pulmonary thromboembolism. MATERIALS AND METHODS:
      Between August 1990 and May 2005, 12 consecutive patients with acute and chronic
      pulmonary thromboembolism underwent open pulmonary thromboembolectomy at Yonsei
      Cardiovascular Center. Their mean age was 47.5 years, and 7 of the patients were
      female. Among 12 patients, 5 had acute onset, and 7 had chronic disease, and 9
      patients were associated with deep venous thrombosis. Extent of pulmonary
      embolism was massive in 3 patients with hemodynamic instability, and submassive
      in 8 patients. Preoperative echocardiogram revealed elevated right ventricular
      pressure in all patients, and 7 patients were in NYHA functional class III or IV.
      Pulmonary thromboembolectomy was performed in all patients under total
      circulatory arrest. RESULTS: There were 2 hospital deaths (16.7%). Among the
      patients who survived, mean right ventricular pressure was decreased
      significantly from 64.3 mmHg to 34.0 mmHg with improvement of NYHA functional
      class. CONCLUSION: Open pulmonary thromboembolectomy is thought to be an
      immediate and definitive treatment for massive pulmonary embolism with optimal
      results. Even though operative mortality is still high, early diagnosis and
      immediate surgical intervention in highly selective patients may improve the
      clinical outcome.

PMID- 19108023
TI  - Transsternal maximal thymectomy is effective for extirpation of cervical ectopic
      thymic tissue in the treatment of myasthenia gravis.
AB  - PURPOSE: Extensive extirpation of cervico-mediastinal adipose tissue increases
      the chance of removing ectopic thymic tissues, thus potentially improving the
      prognosis of myasthenia gravis after thymectomy. We sought to increase efficacy
      and safety of transsternal maximal thymectomy (TSMT). MATERIALS AND METHODS:
      Twenty four patients who underwent TSMT from July 2006 to June 2007 were
      retrospectively reviewed and compared with 73 patients who underwent transsternal
      extended thymectomy (TSET) from January 2004 to May 2006. Ectopic thymic tissue
      in additionally excised cervicomediastinal fat tissue was examined
      histologically. RESULTS: In TSMT group, operation time, amount of cumulative
      drainage and duration of drainage were significantly higher than TSET group.
      However, the difference in hemoglobin count, amount of transfusion, duration of
      intensive care, postoperative hospital stay, and complication rates were not
      statistically different. There was no operative mortality in either group.
      Ectopic thymic tissue was found in 50% of patients. All patients had ectopic
      thymic tissues in the cervical area. Two patients had additional ectopic tissue
      in the aortopulmonary window, and 1 patient had ectopic tissue at posterior of
      the left bracheocephalic vein and lateral of the right phrenic nerve. CONCLUSION:
      TSMT is more effective in the extirpation of ectopic thymic tissues than TSET
      without significant impairment of safety, especially in the cervical area.

PMID- 19108022
TI  - Clinicopathological characteristics of male breast cancer.
AB  - PURPOSE: To investigate clinicopathological characteristics and outcomes of male
      breast cancer (MBC). PATIENTS AND METHODS: We retrospectively analyzed the data
      of 20 MBC patients in comparison with female ductal carcinoma treated at Yonsei
      University Severance Hospital from July 1985 to May 2007. Clinicopathological
      features, treatment patterns, and survival were investigated. RESULTS: MBC
      consists of 0.38% of all breast cancers. The median age was 56 years. The median
      symptom duration was 10 months. The median tumor size was 1.7 cm, 27.8% showed
      node metastasis, and 71.4% were estrogen receptor positive. All 20 cancers were
      arisen from ductal cells. No lobular carcinoma was found. The incidence of stages
      0, I, II, and III in patients were 2, 10, 4, and 3, respectively. All patients
      underwent mastectomy. One with invasive cancer did not receive axillary node
      dissection and stage was not exactly evaluated. Adjuvant treatments were
      determined by pathologic parameters and stage. Clinicopathological parameters and
      survival rates of MBC were comparable to those of female ductal carcinoma.
      CONCLUSION: The onset age of MBC was 10 years older and symptom duration was
      longer than in female patients. No difference in outcomes between MBC and female
      ductal carcinoma suggests that the biology of MBC is not different from that of
      females. Therefore, education, an appropriate system for early detection, and
      adequate treatment are necessary for improving outcomes.

PMID- 19108024
TI  - Allogeneic blood transfusion given before radiotherapy is associated with the
      poor clinical outcome in patients with cervical cancer.
AB  - PURPOSE: To analyze the effect of allogeneic blood transfusion on clinical
      outcome in 119 patients with stage IIB cervical cancer who were treated with
      radiotherapy +/- chemotherapy. PATIENTS AND METHODS: Medical records were
      examined for hemoglobin levels before and during radiotherapy, history of
      allogeneic blood transfusions and the time point when transfusions were given.
      These factors were retrospectively analyzed along with other clinical risk
      factors for influences on the patients' clinical outcomes. RESULTS: Thirty-two
      patients (26.9%) received packed red blood cell transfusion (mean, 3.4 units;
      range, 1-12 units) before or during radiotherapy. Median follow-up period was
      39.3 months (range, 7.6-58.4 months). Patients with history of transfusion showed
      poorer metastasis-free survival and a trend toward poorer overall survival than
      non-transfused patients. When patients who received transfusions were sub-divided
      by the time of transfusion, those who received transfusions before radiotherapy
      had significantly poorer clinical outcome than those who received transfusions
      during radiotherapy. In a multivariable analysis, patients with pretreatment
      transfusion showed a higher risk of distant metastasis (HR = 3.75, 95% CI: 1.28
      12.15, p = 0.017) and decreased overall survival rates (HR = 4.62, 95% CI: 1.15
      18.54, p = 0.031) compared with those of other patients. CONCLUSION: Our results
      suggest that allogeneic blood transfusions given before radiotherapy may be
      associated with higher incidence of distant metastases and decreased survival in
      patients with stage IIB cervical cancer.

PMID- 19108025
TI  - Morphologic variations of the umbilical ring, umbilical ligaments and ligamentum
      teres hepatis.
AB  - PURPOSE: The varied morphology of the umbilical ring and its surrounding
      structures, such as the ligamentum teres hepatis, and the median and medial
      umbilical ligaments, has not been thoroughly investigated. Hence, this study was
      undertaken to clarify the morphologic variations of these structures. MATERIALS
      AND METHODS: The anterior abdominal walls were removed en bloc from 57 adult
      cadavers and dissected under a surgical microscope. RESULTS: One case of
      umbilical hernia was observed, and the remaining 56 umbilical rings were
      classified into 3 types: oval or round in 33 cases (Type A, 59.0%), obliterated
      or slitted in 12 cases (Type B, 21.4%), and completely covered by a connecting
      band between the ligamentum teres hepatis and umbilical ligaments in 11 cases
      (Type C, 19.6%). The median and medial umbilical ligaments were classified into
      four types based on their interrelationships. The most common type was the median
      umbilical ligament terminated by joining one or both medial umbilical ligaments
      (Type II, 41.1%). The ligamentum teres hepatis frequently ended by dividing into
      several branches in the area cranial to the umbilical ring, some of which crossed
      the umbilical ring. The umbilical fascia covered the umbilical ring in 50.0% of
      cases, and the rest either not covering the ring or not existing. CONCLUSION:
      These results are expected to improve our understanding of the anatomy of the
      umbilical area, and further improve treatments of the umbilical hernia.

PMID- 19108027
TI  - Surveillance of stool samples for the presence of Enterobacter sakazakii among
      Korean people.
AB  - PURPOSE: Enterobacter sakazakii (E. sakazakii) infections are an important cause
      of life-threatening meningitis, septicemia, and necrotizing enterocolitis in
      infants. Dried infant formula milk is an important vehicle for E. sakazakii
      infection. E. sakazakii was isolated in Korea from dried infant formula milk.
      Although E. sakazakii infection of infants may occur in Korea, its prevalence has
      not yet been documented. Therefore, we determined the prevalence of E. sakazakii
      and documented symptoms. MATERIALS AND METHODS: Between March and October 2006,
      1,146 stool samples were collected from patients at Uijeongbu St. Mary's
      Hospital. Each fecal swab was dissolved in 10mL of buffered peptone solution, and
      enriched culture was streaked onto Druggan-Forsythe-Iversen (DFI) agar.
      Presumptive E. sakazakii colonies that exhibited a blue-green color during
      culture on DFI medium were selected. The identity of colonies that developed
      yellow pigment during culture on TSA was determined using the Vitek system and
      PCR. RESULTS: We isolated 4 E. sakazakii strains whose 16S rRNA sequence
      alignments had a similarity of 99% with those of 3 E. sakazakii ATCC strains.
      CONCLUSION: This is the first report on isolation of E. sakazakii from stool
      samples and to document the symptoms of Korean patients.

PMID- 19108026
TI  - Effects of 4 weeks recombinant human growth hormone administration on insulin
      resistance of skeletal muscle in rats.
AB  - PURPOSE: Effect of recombinant human growth hormone (rhGH) administration on
      lipid storage, and its subsequent effect on insulin sensitivity have not yet been
      adequately examined. Thus, we investigated the effects of rhGH treatment on
      muscle triglyceride (TG) and ceramide content, and insulin sensitivity after 4
      weeks of rhGH administration in rats. MATERIALS AND METHODS: Fourteen rats were
      randomly assigned to two groups: rhGH injection group (GH, n = 7) and saline
      injection group (CON, n = 7). GH received rhGH by subcutaneous injections (130
      microg.kg(-1).day(-1), 6 days.week(-1)) for 4 weeks, while CON received saline
      injections that were equivalent in volume to GH group. Intramuscular TG and
      ceramide content and hepatic TG content were measured. To determine insulin
      sensitivity, oral glucose tolerance test (OGTT) and muscle incubation for glucose
      transport rate were performed in rats, and used as indicators of insulin
      sensitivity. We also examined plasma lipid profiles. RESULTS: After 4 weeks of
      rhGH treatment, the GH group had higher muscle and liver TG contents than the CON
      (p < 0.05). Ceramide content in GH was significantly greater than that in CON (p
      < 0.05). GH also had higher plasma levels of FFA (p < 0.05), glucose and insulin
      responses during OGTT (p < 0.05), and lower glucose transport rates in submaximal
      insulin concentration (p < 0.05) as compared with CON. Results indicate that rhGH
      treatment is associated with insulin resistance in rats. CONCLUSION: rhGH
      treatment elevated muscle TG and ceramide content, and hepatic TG content. Thus,
      elevation of these compounded by rhGH treatment could contribute to the
      development of insulin resistance in rats.

PMID- 19108028
TI  - Development of monoclonal antibodies against human IRF-5 and their use in
      identifying the binding of IRF-5 to nuclear import proteins karyopherin-alpha1
      and -beta1.
AB  - PURPOSE: IRF-5 is a direct transducer of virus-mediated and TLR-mediated
      signaling pathways for the expression of cytokines and chemokines which form
      homodimers or heterodimers with IRF-7. However, direct IRF-5-specific monoclonal
      antibodies (mAbs) are not available at present. These could be used to further
      evaluate the functions of IRF-5. In this study, we produced and characterized
      three mouse mAbs to human IRF-5. The binding of IRF-5 to nuclear import proteins
      was first identified using a mAb. MATERIALS AND METHODS: His-tagged human IRF-5
      protein spanning amino acid residues 193-257 was used as an antigen and three
      mAbs were produced. The mAbs were tested with ELISA, Western blot analysis (WB),
      immunofluorescent staining (IF), and immunoprecipitation (IP). In addition, the
      nuclear import protein which carried phosphorylated IRF-5 was identified using
      one of these mAbs. RESULTS: MAbs 5IRF8, 5IRF10 and 5IRF24 which reacted with the
      recombinant His-IRF-5(193-257) protein were produced. All mAbs bound to human IRF
      5, but not to IRF-3 or IRF-7. They could be used for WB, IF, and IP studies. The
      binding of phosphorylated IRF-5 to karyopherin-alpha1 and -beta1 was also
      identified. CONCLUSION: Human IRF-5-specific mAbs are produced for studying the
      immunologic roles related to IRF-5. Phosphorylated IRF-5 is transported to the
      nucleus by binding to nuclear import proteins karyopherin-alpha1 and -beta1.

PMID- 19108029
TI  - Idiopathic retroperitoneal fibrosis associated with Hashimoto's thyroiditis in an
      old-aged man.
AB  - Idiopathic retroperitoneal fibrosis (IRPF) is a rare disease characterized by a
      retroperitoneal inflammatory proliferative fibrosing process. Hashimoto's
      thyroiditis is the most common inflammatory condition of the thyroid gland; and
      is a frequently-occurring autoimmune disorder manifesting predominantly in middle
      aged women. We report a rare association of IRPF with Hashimoto's thyroiditis in
      a 67-year-old man demonstrating good response to steroid therapy.

PMID- 19108031
TI  - Successful catheter ablation of atrial tachycardia originating from the non
      coronary aortic sinus.
AB  - We report a rare case of atrial tachycardia originating from the non-coronary
      aortic sinus. After failed radiofrequency (RF) energy applications at right His
      bundle region, the complete elimination of atrial tachycardia was achieved with
      an RF energy application in the non-coronary aortic sinus. With the review of
      other papers, this report emphasizes the importance of mapping in the non
      coronary aortic sinus in focal atrial tachycardia near the atrioventricular node
      or near the His-bundle.

PMID- 19108030
TI  - Pleural epithelioid hemangioendothelioma.
AB  - Epithelioid hemangioendothelioma (EHE) is a rare tumor of vascular origin. While
      it can be found in any tissue, it is most often found in lung and liver and
      usually has an intermediate behavior. EHEs originating from pleural tissue have
      been less frequently described than those from other sites. Furthermore, to date,
      all of the cited pleural EHEs were described as highly aggressive. In the present
      report, we describe a rare case of pleural EHE extending to lung and bone in a 31
      year-old woman. The histological diagnosis was confirmed by both conventional
      examination and immunohistochemistry. Her disease stabilized during the 4th
      course of adriamycin (45 mg/m(2), day 1-3), dacarbazine (300 mg/m(2), day 1-3)
      and ifosfamide (2,500 mg/m(2), day 1-3) with mesna, and she survived for 10
      months after the diagnosis.

PMID- 19108032
TI  - Radiofrequency ablation for hepatic metastasis from gastric adenocarcinoma.
AB  - The prognosis for gastric cancer with liver metastasis continues to be poor. We
      present our preliminary findings from 4 cases of liver metastasis from gastric
      adenocarcinomas treated using radiofrequency ablation (RFA). Between 1995 and
      2004, the clinical history and course of 4 patients who underwent radiofrequency
      ablation for liver metastases from gastric cancer were reviewed. Two patients
      with smaller metachronous metastasis are currently alive without recurrence at 16
      and 14 months and the other patients with larger synchronous metastatic lesions
      died after 4 and 12 months after RFA. Although this study was limited to a few
      cases and had a short follow-up duration, our findings suggest that RFA may
      provide an alternative treatment modality for liver metastasis resulting from
      gastric adenocarcinoma. Additional study is needed with a larger group of
      patients and longer follow up to evaluate the efficacy of RFA.

PMID- 19108033
TI  - Gastric schwannoma.
AB  - Schwannomas, also known as neurinomas or neurilemmomas, are generally benign,
      slow-growing neoplasms originating in any nerve that has a Schwann cell sheath.
      These neoplasms are rare among the spindle cell mesenchymal tumors of the
      gastrointestinal tract, but develop most commonly in the stomach representing
      0.2% of all gastric tumors. We present the case of a 57-year-old female patient
      with a large schwannoma in the stomach that was palpable in the abdomen. She
      underwent subtotal gastrectomy under suspicion of gastrointestinal stromal tumor
      (GIST), but post-operative histopathological and immunohistochemical findings
      showed a fascicular arrangement of spindle cell with pallisading nuclei, and
      positive for S-100 protein with negative smooth muscle actin (SMA). These results
      confirmed schwannoma as the diagnosis.

PMID- 19108034
TI  - A case of acute hepatitis with Mycoplasma pneumoniae infection and transient
      depression of multiple coagulation factors.
AB  - We report a case of acute severe hepatitis with Mycoplasma pneumoniae (M.
      pneumoniae) infection and transient depression of multiple coagulation factors. A
      5-year-old boy, previously healthy, was admitted with pneumonia. M. pneumoniae
      infection was confirmed by serology testing. Liver enzymes were elevated on
      admission without any past medical history. After treatment with azithromycin for
      3 days, pneumonia improved, but the hepatitis was acutely aggravated. Partial
      thromboplastin time (PTT) was prolonged and depression of multiple coagulation
      factors developed. Liver biopsy revealed features consistent with acute
      hepatitis. A week later, liver enzymes were nearly normalized spontaneously.
      Normalization of prolonged PTT and coagulation factors were also observed several
      months later. This may be the first case of transient depression of multiple
      coagulation factors associated with M. pneumoniae infection.

PMID- 19108035
TI  - Retraction: Jhin-Soo Pyen, et al. Tic convulsif caused by cerebellopontine angle
      schwannoma. Yonsei Med J 2001;42:255-7.

PMID- 19108036
TI  - [Few consequences for the perpetrator in acid burning cases].

PMID- 19108037
TI  - Susac syndrome--a report of cochlear implantation and review of otologic
      manifestations in twenty-three patients.
AB  - OBJECTIVE: Susac syndrome is a disease condition of unknown cause consisting of
      vestibulocochlear dysfunction, retinopathy, and multifocal encephalopathy derived
      from microangiopathy of the ear, retina, and brain, respectively. We present a
      unique case of bilateral cochlear implantation in a Susac syndrome patient and
      seek to describe in detail the specific nature of the otologic manifestations of
      this disease. STUDY DESIGN: Clinical records of 23 patients diagnosed with Susac
      syndrome were reviewed. Analysis included demographics, clinical course, and
      audiometric data. An additional review of relevant vestibulocochlear data is
      undertaken among the approximately 100 previously reported cases. RESULTS: Of the
      23 patients with Susac syndrome, 19 (83%) were women. Mean age was 36 years,
      ranging from 19 to 69 years. Ten patients (43.5%) reported a fluctuating hearing
      loss, 14 (61%) reported tinnitus, and 13 (56.5%) noted vertigo. Eleven patients
      (48%) presented with bilateral symptoms, and 12 (52%) were unilateral. In the 34
      affected ears, the pure-tone average was 41.5 dB, and the mean percent hearing
      loss was 26.4%. Forty-seven percent of the affected ears had American Academy of
      Otolaryngology-Head and Neck Surgery hearing classification type A. Only 26.5% of
      the affected ears had 100% word recognition. Statistical analysis supported an
      overall "upsloping" pattern of hearing loss. Bilateral simultaneous cochlear
      implantation was successful in restoring significant hearing in our patient.
      CONCLUSION: Susac syndrome is a rare and potentially devastating disease. Hearing
      loss is quite variable. Low- and mid-range frequencies seem to be most commonly
      affected. Patients whose hearing loss meets criteria should be considered for
      cochlear implantation.

PMID- 19108039
TI  - [Scientific research on alternative medicine].

PMID- 19108040
TI  - Dendritic cell immunobiology and potential roles in immunotherapy.
AB  - Owing to the importance of dendritic cells (DC) in the induction and control of
      immunity, an understanding of their biology is central to the development of
      potent immunotherapies for cancer, chronic infections, autoimmune disease, and
      induction of transplantation tolerance. This review surveys the heterogeneity of
      DC with regards to their phenotype and developmental origin, and how they
      initiate, modify and regulate the immune response, with emphasis on their
      maturation, migration, antigen-presentation and interaction with T cells and
      other immune cells. Much of this knowledge is obtained through research on murine
      DC. Research on human DC has been hampered by limitations associated with in
      vitro assays and limited access to human tissues. New approaches on human DC
      research are required in order to develop novel strategies for the treatment of
      microbial infections, the control of graft rejection, and the improvement of DC
      based immunotherapeutic protocols for autoimmunity, allergy, and cancer.

PMID- 19108038
TI  - The effects of cochlear implantation on vestibular function.
AB  - OBJECTIVE: Determine the risk posed by cochlear implantation (CI) to the
      labyrinth. STUDY DESIGN: Prospective cohort study. SETTING: Academic tertiary
      referral center. PATIENTS: Thirty-six ears belonging to 35 adult CI candidates
      (mean age, 46 yr; range, 23-69 yr). INTERVENTION: Cochlear implantation. MAIN
      OUTCOME MEASURES: Vestibular function was assessed using the quantitative 3
      dimensional head impulse test (qHIT), clinical head impulse test (cHIT), post
      head shake nystagmus, caloric electronystagmography, vestibular-evoked myogenic
      potentials, dynamic visual acuity, and Dizziness Handicap Inventory. RESULTS: All
      36 ears were tested using qHIT before CI, and 28 ears were tested 4 to 8 weeks
      after CI. qHIT showed that 1 of 28 ears had reduced function. cHIT was 44%
      sensitive and 94% specific for identification of severe-to-profound vestibular
      hypofunction confirmed by qHIT. Post-head shake nystagmus was unchanged in 11 of
      11 subjects. New hyporeflexia was found in 1 of 16 electronystagmography-tested
      ears. Vestibular-evoked myogenic potential showed either a disappearance of
      response or an increase in threshold by greater than 10 dB in 5 of 16 ears.
      Passive dynamic visual acuity showed no change in 16 of 16 ears. Dizziness
      Handicap Inventory scores worsened in 3 of 28 and improved in 4 of 28 subjects.
      CONCLUSION: Although small, the observed rate of labyrinthine injury was
      comparable to that for other risks of CI. Thus, it is important to educate CI
      candidates regarding possible risk to balance function, particularly when CI of
      an "only balancing ear" is contemplated. cHIT is useful for detecting severe high
      frequency vestibular hypofunction and should be part of the pre-CI physical
      examination.

PMID- 19108041
TI  - The extrapolation problem and how population modeling can help.
AB  - We argue that population modeling can add value to ecological risk assessment by
      reducing uncertainty when extrapolating from ecotoxicological observations to
      relevant ecological effects. We review other methods of extrapolation, ranging
      from application factors to species sensitivity distributions to suborganismal
      (biomarker and "-omics") responses to quantitative structure-activity
      relationships and model ecosystems, drawing attention to the limitations of each.
      We suggest a simple classification of population models and critically examine
      each model in an extrapolation context. We conclude that population models have
      the potential for adding value to ecological risk assessment by incorporating
      better understanding of the links between individual responses and population
      size and structure and by incorporating greater levels of ecological complexity.
      A number of issues, however, need to be addressed before such models are likely
      to become more widely used. In a science context, these involve challenges in
      parameterization, questions about appropriate levels of complexity, issues
      concerning how specific or general the models need to be, and the extent to which
      interactions through competition and trophic relationships can be easily
      incorporated.

PMID- 19108042
TI  - A novel method for predicting chronic nickel bioavailability and toxicity to
      Daphnia magna in artificial and natural waters.
AB  - In the present study, the individual effects of Ca, Mg, and pH on the chronic
      toxicity of Ni to Daphnia magna were examined in a series of 21-d reproduction
      tests in synthetic test solutions. Based on the linear increase of 21-d median
      effective concentrations expressed as Ni2+ activity (21-d EC50Ni2+) with
      increasing activities of Ca2+ and Mg2+, the effects of Ca and Mg were modeled
      according to single-site competition with log KCaBL = 3.53 and log KMgBL = 3.57
      (BL = biotic ligand). Because the increase of 21-d EC50Ni2+ with increasing H+
      activity was nonlinear, the effect of pH could not be described appropriately by
      single-site competition between Ni2+ and H+. Instead, the effect of pH was
      modeled based on an empirical linear relationship between pH and 21-d EC50pNi2+*
      (equal to -log [21-d EC50Ni2+ corrected for the presence of Ca and Mg]) and was
      superimposed on the effects of Ca and Mg. For all test solutions used for model
      development, the developed model predicted the observed 21-d EC50 expressed as
      dissolved Ni concentration with an error of less than a factor of two. The
      importance of dissolved organic carbon in protecting D. magna against chronic Ni
      toxicity was demonstrated by conducting 21-d reproduction tests in a series of Ni
      spiked natural waters. Because the model tended to systematically overestimate
      chronic Ni toxicity in these natural waters, it was further optimized to yield
      more accurate predictions in natural waters. Although some room still exists for
      improvement, the developed model is, to our knowledge, the first to present a
      useful tool for assessing the risk of Ni to aquatic invertebrates.

PMID- 19108043
TI  - Accuracy of chronic aquatic toxicity estimates determined from acute toxicity
      data and two time-response models.
AB  - Traditionally, chronic toxicity in aquatic organisms and wildlife has been
      determined from either toxicity test data, acute to chronic ratios, or
      application of safety factors. A more recent alternative approach has been to
      estimate chronic toxicity by modeling the time course of mortality as determined
      in standard acute toxicity tests, but these approaches have received limited
      validation. The accuracy of chronic toxicity estimates from two time-response
      models, linear regression analysis (LRA) and accelerated life testing (ALT), was
      investigated using a dataset of more than 150 matched species pairs of standard
      acute toxicity test data and measured chronic no-observed-effect concentrations
      (NOECs). Chronic survival was more accurately modeled by both ALT (accuracy, 69%)
      and LRA (accuracy, 76%) than was reproduction, growth, or the most sensitive
      endpoint (accuracy, 50-60%). In general, LRA estimates of chronic toxicity were
      less conservative than ALT estimates, with 66 to 79% of LRA estimates being
      greater than the measured NOEC. Acute datasets with early mortality produced
      estimates of chronic survival that were more accurate (ALT, 92%; LRA, 89%)
      compared to all datasets but were less conservative (84% of ALT estimates were
      overestimated vs 93% of LRA estimates). Acute datasets with late mortality
      resulted in poor ALT and LRA estimates of chronic toxicity for all endpoints.
      Additional survival time measurements did not improve the accuracy of ALT or LRA
      estimates of chronic toxicity over the standard four acute measurement times (24,
      48, 72, and 96 h). The time course of mortality should be considered when
      applying time-response models to estimate chronic aquatic toxicity, with greater
      accuracy likely for chronic survival than for growth or reproduction.

PMID- 19108044
TI  - Sleepinog in order. While the IOM eyes more rest for resident doctors, some decry
      costs, say patient risk would rise.
AB  - The Institute of Medicine recommended last week raising the bar on limiting
      residents' duty hours. However, critics contend that doing so would put patients
      at risk for poor or unsafe care. "If someone needs a surgeon in the middle of the
      night, we don't say 'Sorry, there's nobody here,' "said Carol Rumack, left, of
      the University of Colorado.

PMID- 19108045
TI  - Healthcare 'swaps' out. Industry pays millions as hedges fizzle in market.

PMID- 19108046
TI  - Pension problems. Systems, hospitals forced to make contributions.

PMID- 19108047
TI  - Patient-safety efforts narrowed. New study questions rapid-response teams'
      efficacy.

PMID- 19108048
TI  - Pushing back the curtain. Cleveland Clinic, UPenn disclose doc agreements.

PMID- 19108049
TI  - Radiologists study prevention. Society's annual meeting focuses on 'doing no
      harm'.

PMID- 19108050
TI  - Mark of zero. Providers, patient-safety advocates brainstorm on decreasing
      errors, bad attitudes.

PMID- 19108051
TI  - Raising the industry to the bar. Chassin hopes to reproduce other industries'
      levels of effectiveness.

PMID- 19108052
TI  - Release point. Release of information industry still trumping EHRs.

PMID- 19108053
TI  - Local managers will get free choice of quality measures.

PMID- 19108054
TI  - Obesity leaves eating disorders in the shade.

PMID- 19108055
TI  - Obama's first steps.

PMID- 19108056
TI  - How can we help the helpless?

PMID- 19108057
TI  - Data briefing. Mapping inequality unmasks variations.

PMID- 19108058
TI  - Compensation culture. Do patients justice.
AB  - Complexity of cases means some negligence claims against the NHS take years to
      settle. Many patients or relatives want only an apology, not money. Surgery is
      subject to the highest number of claims, and fear of complaints can deter medics
      from innovating.

PMID- 19108059
TI  - Quick off the mark for 18-week win.

PMID- 19108060
TI  - Bully for you.

PMID- 19108061
TI  - Feedback. Critical mass.

PMID- 19108062
TI  - Pivotal times.

PMID- 19108063
TI  - Electronic data. Standard bearers.

PMID- 19108064
TI  - Role playing. Winner takes all.

PMID- 19108065
TI  - Data briefing. Identifying coding inconsistencies.

PMID- 19108066
TI  - Age of consent.

PMID- 19108067
TI  - Marketing. Make it snappy.

PMID- 19108068
TI  - Incentivising quality.

PMID- 19108069
TI  - Spread of excitation measurements for the detection of electrode array foldovers:
      a prospective study comparing 3-dimensional rotational x-ray and intraoperative
      spread of excitation measurements.
AB  - OBJECTIVE: The optimal positioning of electrode arrays in the cochlea is
      extremely important. Our standard approach is to use a 3-dimensional rotational x
      ray for the intraoperative determination of the position of the electrode array.
      We wanted to see if spread of excitation (SOE) is useful for determining the
      electrode array position within the cochlea. STUDY DESIGN: Prospective blind
      study design. SETTING: Tertiary University Referral Center (Cochlear Implantation
      Center Amsterdam-Academic Medical Center, University of Amsterdam). PATIENTS:
      Seventy-two implanted ears with a Cochlear Freedom device. INTERVENTION: After
      cochlear implantation, we compared the 3-dimensional rotational x-ray imaging and
      SOE measurements. The investigators were blinded for the intraoperative surgeon
      findings and also for the imaging findings. OUTCOME MEASURE(S): Electrode array
      foldovers within the cochlea and the reliability of the SOE measurements.
      RESULTS: We placed implants in 72 ears in this study, and all procedures seemed
      to be surgically uneventful. To our surprise, we discovered 4 electrode foldovers
      in this group. Of the 4 foldovers, 3 were corrected intraoperatively. CONCLUSION:
      We found that intraoperative imaging and/or electrophysiologic measurements such
      as the SOE provide very useful information regarding electrode position within
      the cochlea. Spread of excitation is effective in detecting electrode array
      foldovers if the audiologist is experienced. Some software modifications are
      suggested.

PMID- 19108070
TI  - Inside-out technique cholesteatoma surgery: a retrospective long-term analysis of
      604 operated ears between 1992 and 2006.
AB  - OBJECTIVE: To retrospectively present the experience with 586 patients or 604
      ears operated for cholesteatoma. PATIENTS: All patients, adults and children,
      with histologically confirmed cholesteatoma and a mean age of 36 years (3 to 86
      yr). INTERVENTION: With the inside-out technique, cholesteatoma is eradicated
      from the epitympanum toward the mastoid: small cholesteatoma is removed by a
      transcanal approach, and medium-sized cholesteatoma is removed by a
      retroauricular atticotomy and cartilaginous reconstruction of the canal wall. An
      extended cholesteatoma is eradicated by a classical canal wall down radical
      cavity. A simultaneous reconstruction of the middle ear by tympano-ossiculoplasty
      is performed. MAIN OUTCOME MEASURES: Postoperative anatomic results with regard
      to recurrence, intactness of the tympanic membrane, and condition of the ear
      site. Auditory performance including air-bone gap, auditory threshold and
      improvement of hearing. RESULTS: A complete removal of cholesteatoma in 93% of
      adults and 87% of children (mean postoperative follow-up, 10 yr; range, 2-15 yr)
      was achieved, with 95% dry ears and a mean air-bone gap of less than 30 dB in 78%
      postoperatively. Nine percent of all patients were lost to follow-up. CONCLUSION:
      The inside-out technique allows the safe removal of cholesteatoma according to
      the extent of disease combining the advantages of the canal wall down technique
      with respect to radicality of cholesteatoma removal and of the canal wall up
      technique with respect to functional results, with the added advantage of single
      stage reconstruction.

PMID- 19108071
TI  - Growing vestibular schwannomas: what happens next?
AB  - OBJECTIVE: To determine the subsequent growth patterns in vestibular schwannomas
      shown to be growing on serial imaging. STUDY DESIGN: Retrospective review.
      SETTING: Tertiary academic referral center. PATIENTS: Patients with tumors that
      demonstrated growth of greater than 1 mm/yr between 2 consecutive scans (magnetic
      resonance or computed tomography) and had at least 1 follow-up scan were
      included. Patients with neurofibromatosis were excluded. INTERVENTION(S): Review
      of radiographic images (magnetic resonance imaging scans) or neuroradiologists'
      reports when the images were unavailable. MAIN OUTCOME MEASURE(S): Maximum
      dimension along the axis of the internal auditory canal was measured for
      intracanalicular tumors, whereas for extracanalicular tumors, maximal dimension
      along any orientation was used. A significant difference in dimension was defined
      to be greater than 1 mm/yr, positive or negative. RESULTS: Thirty-six patients
      were included in the study; 47% were women and with an average age of 60.2 years.
      The average follow-up period after growth was identified was 2.1 years. Of the
      growing tumors, 63.9% continued to grow, 30.6% stayed the same size, and 5.6%
      regressed in size. CONCLUSION: Most vestibular schwannomas identified to be
      growing are likely to continue to grow on subsequent serial imaging. These
      results are useful in clinical decision making and counseling patients with
      growing vestibular schwannomas.

PMID- 19108073
TI  - Chemotherapeutic action of dyes in typhus infection of mice.

PMID- 19108072
TI  - Foreword.

PMID- 19108074
TI  - Amidines, guanidines, and adrenaline inactivation in the liver.

PMID- 19108075
TI  - Analgesic action of pethidine derivatives and related compounds.

PMID- 19108077
TI  - Chemotherapeutic action of amidine and phenanthridinium compounds in T.
      congolense infections.

PMID- 19108076
TI  - The effect of ethanol, methanol, paraldehyde, and acetone on the pressure of the
      cerebrospinal fluid of the dog.

PMID- 19108078
TI  - Assessment of analgesic activity in new synthetic drugs.

PMID- 19108080
TI  - Automatic apparatus for pharmacological assays on isolated preparations.

PMID- 19108079
TI  - Methyl-thiouracil and thiouracil as antithyroid drugs.

PMID- 19108081
TI  - Sulphonamides in the treatment of caecal coccidiosis of chickens.

PMID- 19108082
TI  - Variation in the toxicity of phosgene for small animals with the duration of
      exposure.

PMID- 19108083
TI  - Synthetic substitutes for quinidine.

PMID- 19108084
TI  - The pharmacology of basic esters of thiazole carboxylic acids.

PMID- 19108085
TI  - The testing of drugs against exoerythrocytic forms of P. gallinaceum in tissue
      culture.

PMID- 19108086
TI  - Experimental diabetes: the effect of ligation of the pancreatic duct upon the
      action of alloxan in rabbits.

PMID- 19108087
TI  - Actions of cyanate.

PMID- 19108088
TI  - The action of mersalyl, calomel, and theophylline sodium acetate on the kidney of
      the rat.

PMID- 19108089
TI  - Method for the estimation of barbituric and thiobarbituric acids in biological
      materials.

PMID- 19108090
TI  - Kemithal: a new intravenous anaesthetic.

PMID- 19108091
TI  - Some pharmacological and chemotherapeutic properties of notatin.

PMID- 19108092
TI  - Changes in cis- and trans- stilbamidine solutions on exposure to light.

PMID- 19108093
TI  - Experimental diphtheroid infections of the rabbit's eye and their treatment.

PMID- 19108094
TI  - The toxicity of alkyl-bis(beta-chloroethyl)amines and of the products of their
      reaction with water.

PMID- 19108096
TI  - The pharmacological properties of alpha:beta-dihydroxy-gamma-(2-methylphenoxy)
      propane (myanesin).

PMID- 19108095
TI  - A method for the evaluation of analgesic activity using rats.

PMID- 19108097
TI  - The synthesis, toxicity, and anaesthetic potency of two new local anaesthetics.

PMID- 19108098
TI  - The antihistamine substance 2786 R.P.

PMID- 19108099
TI  - The toxicity of arsine administered by intraperitoneal injection.

PMID- 19108100
TI  - A method of estimating curare-like activity on the isolated phrenic nerve
      diaphragm preparation of the rat.

PMID- 19108101
TI  - Effect of streptomycin on experimental tuberculosis in guinea-pigs.

PMID- 19108102
TI  - The relationship between survival time and dosage with certain toxic agents.

PMID- 19108103
TI  - The effect of exposure to sub-lethal doses of phosgene on the subsequent l(ct)50
      for rats and mice.

PMID- 19108104
TI  - The cholinesterase inhibiting action of fluorophosphonates.

PMID- 19108105
TI  - The possibility of toxic effects from 2:3-dimercaptopropanol in conditions of
      impaired renal or hepatic function.

PMID- 19108106
TI  - The relative activity of prostigmine homologues and other substances as
      antagonists to tubocurarine.

PMID- 19108107
TI  - The biological estimation of substances used in treating cestode infestations.

PMID- 19108108
TI  - The affinity of atropine-like esters for esterases.

PMID- 19108109
TI  - The inhibition of esterases by paludrine.

PMID- 19108110
TI  - Oxidation of adrenaline in alkaline solution.

PMID- 19108111
TI  - The action of acetylcholine, adrenaline, and other substances on the refractory
      period of the rabbit auricle.

PMID- 19108112
TI  - The inhalation of hexoestrol.

PMID- 19108114
TI  - The effects of pyrimidine sulphonamide derivatives upon the blood-clotting system
      and testes of chicks and the breeding capacity of adult fowls.

PMID- 19108113
TI  - The absorption of some sulphaguanidine derivatives in mice.

PMID- 19108115
TI  - The comparison of respiratory stimulant drugs.

PMID- 19108116
TI  - 2-p-Aminobenzenesulphonamido-4:6-dimethoxypyrimidine: experimental evaluation.

PMID- 19108117
TI  - 2-p-Aminobenzenesulphonamido-4:6-dimethoxypyrimidine absorption and excretion in
      man: With notes on a clinical trial in pneumonia.

PMID- 19108118
TI  - An assessment of the value of suggested therapies for leucopenia.

PMID- 19108119
TI  - Selective inhibition of pseudo-cholinesterase by diisopropyl fluorophosphonate.

PMID- 19108120
TI  - A preliminary report of the toxicity and the associated blood concentrations of
      paludrine in laboratory animals.

PMID- 19108121
TI  - Some actions of beta-hydroxy-alphabeta-diphenylethylamine.

PMID- 19108122
TI  - The therapeutic action of some known amoebicides in rats.

PMID- 19108123
TI  - The technique of testing chemotherapeutic action on plasmodium gallinaceum.

PMID- 19108124
TI  - The toxicity of alkyl fluorophosphonates in man and animals.

PMID- 19108125
TI  - The mode of action of myanesin.

PMID- 19108126
TI  - The use of drug antagonists for the identification and classification of drugs.

PMID- 19108127
TI  - The influence of calcium and potassium ions on the toxicity of ouabain.

PMID- 19108128
TI  - The blocking effect of bis-triethyl-ammonium salts on transmission in the
      perfused superior cervical ganglion of the cat.

PMID- 19108129
TI  - The persistence in the blood stream of some analogues of
      sulphadimethoxypyrimidine.

PMID- 19108130
TI  - A method for recording peristalsis in isolated intestine.
AB  - A method is described for studying peristalsis in isolated pieces of guinea-pig
      ileum. Records are obtained of longitudinal contractions, intraluminal pressure
      and volume of fluid expelled.

PMID- 19108131
TI  - The 5-hydroxytryptamine content of mouse brain and whole mice after treatment
      with some drugs affecting the central nervous system.
AB  - A number of drugs were examined for their ability to change the concentration of
      5-hydroxytryptamine in mouse brain and in whole mice treated with 5
      hydroxytryptophan. After beta-phenylisopropylhydrazine or iproniazid, two
      inhibitors of monoamine oxidase, the brain 5-hydroxytryptamine rose to a maximum
      value in 8 hr., after which it declined, although a slight rise remained for as
      long as 6 days. Dose-effect relationships, determined 6 hr. after administration,
      showed beta-phenyl-isopropylhydrazine to be approximately 60 times as effective
      as iproniazid in raising the brain 5-hydroxytryptamine. When mice were given 5
      hydroxytryptophan and the amine content of the whole mice estimated, pretreatment
      with beta-phenylisopropylhydrazine increased their 5-hydroxytryptamine content
      whereas pretreatment with iproniazid did not change it. The concentration of the
      amine in mouse brain and in whole mice was lower after reserpine, but was raised
      when reserpine and beta-phenylisopropylhydrazine were given together. A small
      rise in brain 5-hydroxytryptamine was found after chlorpromazine; when
      chlorpromazine was given with iproniazid, however, the resulting increase was
      less than that found after iproniazid alone. Brain 5-hydroxytryptamine was
      unaltered after prolonged treatment with morphine.

PMID- 19108132
TI  - Ganglion-blocking properties of atropine-like drugs.
AB  - The ganglion-blocking properties of atropine, atropine methyl nitrate,
      oxyphenonium, poldine, methantheline and propantheline have been examined and
      compared with those of hexamethonium, mecamylamine, pentolinium and
      tetraethylammonium. The ganglion-blocking activity was assessed by stimulating
      the preganglionic nerve to the superior cervical ganglion and recording directly
      the percentage depression in the postganglionic action potentials. In this way
      any ambiguity due to the peripheral actions of the drugs was removed. As a group
      the atropine-like compounds are not markedly less potent than the ganglion
      blocking agents, but their action is relatively transient. This work suggests
      that the ganglion-blocking action of atropine-like substances plays no part in
      their therapeutic effects.

PMID- 19108134
TI  - BRITISH PHARMACOLOGICAL SOCIETY and SCANDINAVIAN PHARMACOLOGICAL SOCIETY.

PMID- 19108133
TI  - The ganglion-blocking activity of aminobicyclo[2,2,1]heptanes (congeners of
      mecamylamine) and bicyclo[3,2,1]azaoctanes (bridged congeners of pempidine).
AB  - The structural requirements for strong ganglion-blocking activity and long
      duration of action amongst some lower homologues of mecamylamine, together with
      the discovery of similar activities amongst isomers with enlarged ring
      structures, are described. In both series of compounds it was found that the
      successive introduction of C-methyl groups surrounding the nitrogen atom resulted
      in a progressive increase in ganglion-blocking activity and duration of action.

PMID- 19108135
TI  - The release of acetylcholine from mammalian motor nerve endings.
AB  - The release of acetylcholine from rat and guinea-pig isolated diaphragm
      preparations stimulated through the phrenic nerve was optimal at 37 degrees in
      Krebs solution with 5x10(-6) neostigmine methylsulphate. The amount of
      acetylcholine released by a 20 min. tetanus was reduced by cooling. At
      frequencies of stimulation above 6/sec. the release was less than that predicted.
      This "failure" was unaffected by the addition of 1x10(-6) choline. The
      acetylcholine release declined with continued stimulation at 25/sec. In the
      absence of nerve stimulation, there was a small continuous resting release of
      acetylcholine which seemed to originate in the muscle fibres. These results are
      discussed in the light of current electrophysiological knowledge of the quantal
      release of acetylcholine.

PMID- 19108136
TI  - Peripheral vascular effects of bretylium tosylate in man.
AB  - After intra-arterial infusion of bretylium tosylate (12.5 mg.), the reflex
      changes in vasoconstrictor tone which normally occur in the forearm with body
      cooling, positive pressure breathing, the Valsalva manoeuvre and postural change
      were greatly reduced or abolished. Reflex vasodilatation mediated by cholinergic
      fibres in response to body heating or to emotional stress was little affected. It
      was concluded that bretylium can selectively block the activity of sympathetic
      noradrenergic fibres without causing a similar block of sympathetic cholinergic
      fibres. As the responses to intravenous or intra-arterial infusions of adrenaline
      or noradrenaline were not reduced after bretylium, it was concluded that
      bretylium interferes with the activity of noradrenergic fibres rather than with
      the activity of the noradrenaline released at the nerve ending. After bretylium
      infusion, forearm and hand blood flow did not often rise to levels characteristic
      of full release of vasoconstrictor tone. As infusion of bretylium into a nerve
      blocked forearm resulted in a pronounced reduction in flow, it is concluded that
      bretylium also has a constrictor effect on blood vessels. The state of the
      vessels following an infusion of bretylium appears to depend on the balance
      between this constrictor action and the longer-acting sympathetic blocking
      effect.

PMID- 19108137
TI  - The antagonism of muscle relaxants by ambenonium and methoxyambenonium in the
      cat.
AB  - The ability of ambenonium and a methoxy analogue to antagonize paralysis produced
      either by tubocurarine or by decamethonium has been studied in the tibialis
      anterior muscle of the cat under chloralose anaesthesia. In small doses, both
      oxamides facilitated neuromuscular transmission, but in larger doses they
      depressed the sensitivity of the motor end plates to depolarizing substances and
      it is considered that this latter action is sufficient to account for their anti
      decamethonium action. Although both compounds possess anticholinesterase
      activity, there was found to be no correlation between their relative abilities
      to antagonize tubocurarine paralysis and their abilities to inhibit muscle
      cholinesterase in vitro.

PMID- 19108138
TI  - The effect of diet on the 5-hydroxytryptamine content of the small intestine and
      other organs in rats and mice.
AB  - In rats, a diet of meat or liver caused a rise in the amount of 5
      hydroxytryptamine in the small intestine, an increase in the weight of the
      intestine and a 10-fold increase in anaerobic bacteria in the rectum. A diet
      containing added tryptophan did not affect tissue levels of 5-hydroxytryptamine
      in rats, but in mice there was a rise of 5-hydroxytryptamine in various tissues.
      The significance of these findings is discussed together with the possible role
      of intestinal bacteria in mediating the effects caused by a meat diet. No change
      was observed in the 5-hydroxytryptamine content of brain or in the distribution
      of argentaffin cells in the jejunum as a result of these diets.

PMID- 19108139
TI  - The anticholinesterase activity of some antiadrenaline agents.
AB  - The contractions of the isolated guinea-pig vas deferens in response to
      stimulation of the sympathetic hypogastric nerve were potentiated by low
      concentrations and inhibited by high concentrations of the antiadrenaline agents
      tolazoline, yohimbine, ergotamine, phenoxybenzamine and piperoxan. Eserine
      potentiated the contractions of the vas deferens produced by hypogastric nerve
      stimulation. The cholinesterase activity of an extract of vas deferens was
      decreased by the antiadrenaline agents. The potentiation of responses to
      sympathetic stimulation by antiadrenaline drugs, which also possess
      anticholinesterase activity, can be explained on the basis of a cholinergic
      sympathetic mechanism.

PMID- 19108140
TI  - The anatomical basis of the straub phenomenon.
AB  - The administration of morphine was followed in white mice by a typical Straub
      reaction which consisted of the tail becoming rigid and erected across the back
      of the animal in an S-shaped curve. This reaction was accompanied by
      restlessness, excitability, extension rigidity of the hindlimbs, forcible
      viodance of faeces and prominence of the perineum. The Straub reaction was
      abolished by general anaesthesia with pentobarbitone or ether, by administration
      of tubocurarine, by bilateral section of the muscles causing extension to the
      tail, and by the removal of the circulation to the lower extremity. The reaction
      was modified by unilateral section of the extensor muscles of the tail. Section
      of the spinal cord, decortication, division of the anal sphincter and perineal
      floor, or ablation of the pelvic splanchnic nerves did not suppress the
      appearance of the Straub response. It was concluded that the phenomenon described
      by Straub (1911) was produced mainly by the action of the sacro-coccygeus
      dorsalis muscle, and that it was also necessary that the lumbo-sacral cord with
      its peripheral nervous outflow should be intact and that these functioning units
      should have an adequate circulation.

PMID- 19108141
TI  - Tremor in cats: the effect of administration of drugs into the cerebral
      ventricles.
AB  - In cats, tremor produced by intraperitoneal pentobarbitone sodium or by
      intramuscular chlorpromazine was abolished by injection into the cerebral
      ventricles of a few gamma of adrenaline or noradrenaline, but not of other
      sympathomimetic amines or of anti-Parkinsonian drugs. Chloralose, urethane,
      calcium chloride, and magnesium chloride produced anti-tremor activity when
      administered in this way. When adrenaline or noradrenaline was perfused from a
      lateral ventricle to the aqueduct during pentobarbitone sodium tremor, tremor was
      inhibited when less than 1 mug. had been perfused. Adrenaline was at least four
      times as active as noradrenaline. Isoprenaline inhibited tremor when perfused in
      higher concentrations, but perfusion of ephedrine, amphetamine or of the anti
      Parkinsonian drugs in high concentrations was ineffective. Perfusion of 2 mug. of
      chloralose or of 20 mug. of calcium chloride was sufficient to inhibit tremor.
      Intraventricular injections of 250 to 500 mug. of 5-hydroxytryptamine initiated
      tremor. Possible physiological implications of these findings are discussed.

PMID- 19108142
TI  - Membrane potential changes associated with tachyphylaxis and potentiation of the
      response to stimulating drugs in smooth muscle.
AB  - Conditions which affect the response of smooth muscle to repeated application of
      stimulating drugs have been investigated. In guinea-pig taenia coli, tension
      changes were recorded simultaneously with membrane potential changes using the
      sucrose gap technique. Acetylcholine, histamine, and 5-hydroxytryptamine caused
      depolarization and, after removal of the drug, hyperpolarization which was
      followed by a sequence of damped oscillations of the membrane potential. The
      average rate of depolarization decreased in the order acetylcholine>histamine >5
      hydroxytryptamine. The readiness with which tachyphylaxis occurred increased in
      the order acetylcholine<histamine<5-hydroxytryptamine. When a dose of a
      stimulating drug was repeated, the response obtained depended on the phase of the
      oscillatory potential changes during which it was applied. In general the effect
      was depressed during a phase of polarization and enhanced during a phase of
      depolarization. The degree of tachyphylaxis-or potentiation-depended not only on
      the direction in which the membrane potential changed at the moment of drug
      application, but also on the relation between the rate at which this potential
      change took place and the rate of depolarization caused by the drug. The results
      observed are consistent with the hypothesis that the fluctuating excitability and
      polarization of the smooth muscle membrane is brought about by periodical changes
      in the rate of active ion transport and other stabilizing processes in the cell
      membrane which depend on the rate of metabolic energy supply. The muscle was
      sensitized to acetylcholine and histamine by previous treatment with, or in the
      presence of, 5-hydroxytryptamine.

PMID- 19108143
TI  - A comparative study of hydroxyindole oxidases.
AB  - A comparative study has been carried out of the oxidation of 5-hydroxytryptamine
      and related compounds by the oxidase present in the gill plates of Mytilus edulis
      and of caeruloplasmin, the copper containing oxidase of mammalian plasma. Both
      preparations oxidized indole derivatives carrying a hydroxyl group in the 4-, 5-,
      6-, or 7- position. The oxidation of bufoteni ne was compared with that of its 4-
      and 6-hydroxy analogues; the 4-hydroxy analogue is psil ocine, a naturally
      occurring hallucinogenic compound. Bufotenine and the 6-hydroxy analogue were
      oxidized by both preparations with the formation of brown pigments; psilocine was
      more rapidly oxidized with the appearance of a blue colour. 4-Hydroxytryptamine
      and 7-hydroxytryptamine were also oxidized, the former with the formation of a
      blue compound. The N-1-methyl derivatives of both bufotenine and psilocine were
      also oxidized. The Mytilus preparation acted also on 4-, 5-, and 7
      hydroxytryptophan and on 5-hydroxyindole, none of which was oxidized by
      caeruloplasmin. The Mytilus enzyme also oxidized 5-hydroxyindoleacetic acid.
      Paraphenylenediamine, a very good substrate of caeruloplasmin, was much more
      slowly oxidized by the gill plate enzyme. The evidence suggests that the two
      enzymes catalyse the same reactions, but that the substrate specificity of the
      mammalian oxidase is somewhat more restricted. Both enzymes are "hydroxyindole
      oxidases," not specific for 5-hydroxyindoles alone. Inhibitors of the Mytilus
      oxidase included inhibitors of copper enzymes but not edetate or carbon monoxide.
      The action of pig serum on 5-hydroxytryptamine was due to caeruloplasmin and not
      to amine oxidase.

PMID- 19108144
TI  - The effects of ion changes on the contraction of the rat uterus stimulated by
      oxytocin.
AB  - The contraction of the rat uterus to oxytocin was measured when it was bathed in
      various solutions. Substitution of nitrate or bromide for two-thirds of the
      chloride present increased the size of contractions, while a similar substitution
      of sulphate and sucrose for chloride depressed them. Alteration of the ratio of
      chloride to sodium by substitution of choline for two-thirds of the sodium
      present enhanced the contractions, but this was probably due to the choline per
      se as choline sulphate similarly enhanced the response. Partial replacement of
      both sodium and chloride by sucrose did not alter the size of contractions.

PMID- 19108145
TI  - Cardiovascular actions of phenoxybenzamine.
AB  - Phenoxybenzamine increased the force of contraction and rate of the heart and
      lowered the blood pressure of dogs in pentobarbitone anaesthesia. This was
      preceded by depression of cardiac contractile force and a rise in blood pressure
      when phenoxybenzamine was injected following ganglion-blocking drugs or atropine.
      The positive inotropic and chronotropic and the hypertensive effects of
      phenoxybenzamine were prevented by pretreatment with reserpine or guanethidine.

PMID- 19108146
TI  - Effect of antibiotics on the 5-hydroxytryptamine content of the small intestine
      and other organs in rats and mice.
AB  - Rats and mice were given antibiotics orally and by subcutaneous injection and the
      effects on tissue levels of 5-hydroxytryptamine and intestinal bacteria were
      studied. In mice it was found that antibiotics which caused a large reduction in
      the bacterial flora of the intestine when given orally also caused a significant
      increase in intestinal 5-hydroxytryptamine. In rats, neomycin caused a reduction
      in the urinary excretion of 5-hydroxyindoleacetic acid. In both rats and mice,
      many antibiotics caused a significant reduction in the weight of the spleen.

PMID- 19108147
TI  - Salicylate and liver glutathione.
AB  - The effects of sodium salicylate, benzoate, gentisate, m- and p-hydroxybenzoates,
      antipyrine, and 2:4-dinitrophenol on the reduced glutathione concentration of rat
      liver were determined. An increase in concentration in the male, but not in the
      female, rats was found after salicylate, benzoate and gentisate; after
      antipyrine, a comparable increase occurred in the females only. There is a
      relation, in these compounds, between capacity to increase the concentration of
      reduced glutathione in the rat liver in one sex and therapeutic activity in
      rheumatic fever.

PMID- 19108148
TI  - Metabolism of [c]-histamine in heart-lung-liver preparations of cats.
AB  - The metabolism of injected [(14)C]-histamine was studied in heart-lung-liver
      preparations and heart-lung preparations from cats. When the liver was included
      in the circulation the injected histamine was rapidly eliminated from the blood,
      some of its metabolites appearing in the blood within 2 min after the injection.
      More than 70% of the injected histamine was metabolized to 1-methylimidazol-4
      ylacetic acid. In the heart-lung preparations [(14)C]-histamine disappeared much
      more slowly from the blood and the major metabolite was 4-(2-aminoethyl)-1
      methylimidazole (methylhistamine). Less than 4% of the injected (14)C was
      recovered in the form of imidazol-4(or 5)-ylacetic acid. In none of the
      experiments was there any measurable formation of acetylhistamine.

PMID- 19108149
TI  - Pharmacological properties of 3-phenyl-5beta diethylaminoethyl-1,2,4-oxadiazole.
AB  - The general pharmacological properties of Oxolamine (3-phenyl-5beta
      diethylaminoethyl-1,2,4-oxadiazole) are described. The antitussive activity of
      this drug is more apparent in tests involving a diffuse stimulation of the
      bronchial tree than with electrical stimulation of the superior laryngeal nerve.
      These results suggest a predominantly peripheral mechanism of action. Oxolamine
      also possesses analgesic-anti-inflammatory, local anaesthetic and antispasmodic
      properties. The acute and chronic toxicities of Oxolamine are low, and the
      experimental results indicate the absence of side effects. The possibility that
      the antitussive activity is related to the other pharmacological properties is
      discussed.

PMID- 19108150
TI  - Action of 5,5-diethyl-1,3-oxazine-2,4-dione (dioxone) on respiration and
      circulation.
AB  - The action of 5,5-diethyl-1,3-oxazine-2,4-dione (dioxone) has been studied in
      rats, rabbits, cats and dogs. Dioxone produced a marked stimulation of
      respiration in anaesthetized, decerebrate and spinal animals when given in doses
      that did not induce convulsions. This effect was generally accompanied by a rise
      in blood pressure, which was more marked in cats than in dogs and rabbits.
      Dioxone antagonized the respiratory and circulatory depression due to
      pentobarbitone. The respiratory stimulating effect of dioxone appears to be 2 or
      3 times greater than that of leptazol, and comparable to that of megimide. Like
      leptazol, nikethamide and megimide, dioxone has no direct effect on cardiac
      function. Dioxone did not elicit respiratory and blood pressure changes when
      allowed to come in contact with the carotid sinus receptors. Dioxone enhanced the
      reflex excitability of bulbar centres, as demonstrated by the increase in
      respiratory response either to temporary common carotid artery occlusion in dogs
      or to electrical stimulation of the central cut end of Hering's nerve in the cat.
      Dioxone also reduced the inhibition of respiration induced by electrical
      stimulation of the central cut end of the vagus nerve. Whether this central
      action of dioxone is direct or not cannot at present be elucidated, though a
      section at intercollicular level did not prevent the respiratory stimulation
      produced by this substance.

PMID- 19108151
TI  - Fate of synthetic oxytocin analogues in the rat.
AB  - The disappearance of phe(3)-oxytocin, val(3)-oxytocin and oxytocin from the
      circulation of male rats was shown to be due to qualitatively similar mechanisms,
      that is, it depends on uptake in the kidneys and organs of the splanchnic
      vascular area. However, compared to phe(3)-oxytocin and oxytocin (whose half
      lives were essentially similar) val(3)-oxytocin took twice as long to reach half
      its initial blood concentration. In lactating rats the mammary glands probably
      participated in the uptake of phe(3)-oxytocin, but the rate of disappearance of
      val(3)-oxytocin was not different from that in non-lactating animals. In male
      nephrectomized rats without splanchnic circulation, phe(3)-oxytocin, unlike
      val(3)-oxytocin, was quickly distributed in a volume equal to two-thirds of the
      total body water. Using oxytocin as the standard, val(3)-oxytocin and phe(3)
      oxytocin were more potent when assayed on a superfused uterus or on a rat uterus
      in vivo than when assayed by the pharmacopoeial method (1958) on the isolated
      uterus in an organ bath. The difficulties of assaying oxytocin analogues against
      oxytocin (or the international standard preparation) are discussed.

PMID- 19108152
TI  - Uptake of 5-hydroxytryptamine by platelets.
AB  - Human blood platelets were incubated with 5-hydroxytryptamine and with tryptamine
      and the uptake of each amine measured. The uptake of tryptamine, unlike that of 5
      hydroxytryptamine, was linearly related to the concentration of the amine in the
      surrounding fluid, was similar in amount at 0 degrees and 37 degrees C and varied
      directly with the pH of the solution. When both amines were present together the
      uptake of 5-hydroxytryptamine was depressed. The antagonism of tryptamine was
      found to be competitive, and the possible site of its action is discussed. The
      effect of a number of other substances on the uptake of 5-hydroxytryptamine by
      platelets was examined; of these imipramine, cocaine and chlorpromazine were more
      potent and dihydroergotamine and lysergic acid diethylamide somewhat less potent
      than tryptamine in inhibiting uptake.

PMID- 19108153
TI  - The neuromuscular blocking action of gamma-oxalolaudonium bromide.
AB  - In small animals gamma-oxalolaudonium caused flaccid paralysis; in the cat it
      produced a curare-like rather than a decamethonium-like block of neuromuscular
      transmission. The potency of gamma-oxalolaudonium was only 1/30 to 1/40 that of
      suxamethonium, but the duration of paralysis was very short, being about one-half
      that of equiactive doses of suxamethonium. Successive doses of gamma
      oxalolaudonium were not cumulative and the paralysis could be antagonized by
      neostigmine. gamma-Oxalolaudonium exhibited low toxicity especially in
      artificially ventilated animals, and it did not show ganglionblocking or
      histamine-releasing activity to any large degree.

PMID- 19108154
TI  - Peripheral actions of hexamethonium in relation to the decreasing effects of
      repeated doses on the blood pressure of anaesthetized rats.
AB  - When hexamethonium was given intravenously to anaesthetized rats, the depressor
      response produced by successive doses became less. This effect was not related to
      the duration of anaesthesia and the possible recovery of cardiovascular reflex
      activity. When the rat's own blood was perfused at constant rate through one hind
      limb, successive doses of hexamethonium reduced the hind-limb perfusion pressure
      to the same extent each time, but their effect on the blood pressure of the
      remainder of the animal became less. When the hind limb was perfused at constant
      rate with blood from a separate donor rat, hexamethonium in the donor blood
      produced a very small increase in the vasoconstrictor response to noradrenaline
      in the innervated hind limb but not in the denervated hind limb.

PMID- 19108155
TI  - A note on the distribution of [c]-histamine added to blood.
AB  - (14)C-Labelled histamine was incubated with canine or human blood at 37 degrees
      C. After 1 hr 80 to 100% of the added histamine could be recovered in unchanged
      form. When [(14)C]-histamine was added to whole blood in vitro it tended to
      become equally distributed between the cell and plasma fraction of the blood, and
      when the cell fraction of blood containing [(14)C]-histamine was suspended in
      [(14)C]-histamine-free plasma the labelled histamine tended to become equally
      distributed between cells and plasma. The pattern of distribution of
      intravenously injected [(14)C]-histamine in the blood of anaesthetized dogs
      seemed to be the same as that of histamine added in vitro. The injected histamine
      entered the cell fraction of the blood at a slow rate. These experiments indicate
      that in dog and man the blood cells are of little or no importance for the
      inactivation of histamine released into the circulating blood.

PMID- 19108156
TI  - Sensitivity of the hyperthyroid and hypothyroid mouse to histamine and 5
      hydroxytryptamine.
AB  - Injections of thyroxine sodium increased the sensitivity of mice to histamine,
      the maximal effect occurring after 6 days. The sensitivity to 5-hydroxytryptamine
      was increased to a lesser extent. Hydrocortisone antagonized this effect of
      thyroxine, whereas anti-thyroid drugs alone decreased the sensitivity to
      histamine. Treatment with thyroxine also raised the metabolic rate, the peak
      again being reached after 6 days. As treatment was continued beyond 6 days, the
      adrenal gland enlarged and its secretion probably accounted for the decline in
      the histamine sensitivity.

PMID- 19108157
TI  - The distribution of some quaternary ammonium salts in the peripheral nervous
      system of cats in relation to the adrenergic blocking action of bretylium.
AB  - The concentrations of bretylium in the peripheral nervous system of cats after
      subcutaneous dosage have been compared with those drugs bearing either chemical
      or pharmacological resemblance to bretylium. o-Bromobenzyltrimethylammonium
      iodide (383C57), a chemical homologue of bretylium with feeble adrenergic
      blocking activity, selectively accumulated in adrenergic neurones to attain
      concentrations comparable with those found for bretylium, but it did not persist
      in the neurones. {2-(4-Benzoyl-2,6-dimethylphenoxy)ethyl}trimethylammonium, the 4
      benzoyl derivative of 2,6-xylyl choline ether (172C58), a pharmacological
      analogue of bretylium but with little chemical resemblance, had a less marked
      selective affinity for adrenergic neurones and the concentrations after an
      effective dose were much lower than found for bretylium. Pentacynium {N(1)-5
      cyano-5,5-diphenylpentyl)-N(1)N(1)N(2)-trimethylethylene-1-ammonium-2
      morpholinium di-iodide}, a bis-quaternary ammonium-type ganglion blocking agent,
      had no selective affinity for adrenergic neurones. Bretylium was not displaced
      from adrenergic neurones by a subsequent dose of 172C58. The potency and duration
      of local anaesthetic action of bretylium, 383C57 and 172C58 were roughly parallel
      to the potency and duration of their adrenergic blocking action. The results are
      discussed in relation to the role of selective accumulation in adrenergic
      neurones by bretylium in its adrenergic blocking activity.

PMID- 19108158
TI  - Mechanism of increased susceptibility to fibrillation of the hypothermic
      mammalian heart in situ.
AB  - The susceptibility of auricles and ventricles to fibrillation during hypothermia
      of isolated hearts, and of hearts in situ in anaesthetized cats, was estimated by
      measuring the threshold for the production of fibrillation by electrical
      stimulation. Hypothermia reduced the threshold of in situ hearts, but increased
      the threshold of isolated perfused hearts and of heart-lung preparations. The
      increased sensitivity of in situ hearts to fibrillation could be induced by
      cooling the head only, and was abolished by cutting the vagi. At normal body
      temperature, section of the vagi had no influence on the fibrillation threshold.
      In contrast, cutting the sympathetic increased the fibrillation threshold of in
      situ hearts at normal temperature, but had no influence on the threshold during
      hypothermia. It was concluded that the increased susceptibility of anaesthetized
      animals to fibrillation could be attributed to changes in the central nervous
      control of the heart induced by the cooling of the head.

PMID- 19108159
TI  - Immediate effects of catecholamines on plasma fibrinogen in conscious and
      anaesthetized dogs.
AB  - Adrenaline, noradrenaline, and isoprenaline were injected into dogs and the
      levels of plasma fibrinogen were estimated for up to 90 min. No changes in the
      concentrations of circulating plasma fibrinogen were found following the
      administration of any of the agents. These results do not support the view that
      hyperfibrinogenaemia occurs immediately following injection of adrenaline or that
      changes in fibrinogen concentration are related to alterations in blood pressure.

PMID- 19108160
TI  - Effects of some isomers and analogues of nicotine on junctional transmission.
AB  - A number of isomers and homologues of nicotine, (2-, 3- and 4-pyridylmethyl)- and
      [2-(2-, 3- and 4-pyridyl)ethyl]- dialkylamines and trialkylammonium salts, have
      been prepared. They have been tested for their ability to act like acetylcholine
      in causing contracture of the chick biventer-cervicis and, some of them, for
      their ability to stimulate the superior cervical ganglion of the cat, causing
      contracture of the nictitating membrane. All the compounds have been tested for
      their ability to block transmission on the superior cervical ganglion of the cat
      and on the rat diaphragm preparation, and most of them for ability to inhibit the
      enzymatic hydrolysis of acetylcholine, using an acetone-powder of dog caudate
      nucleus as a source of acetylcholinesterase. The dissociation constants of the
      compounds have been measured by electrometric titration. The dissociation
      constants were used to compute the amount of monovalent ion present in the
      conditions of the biological tests, and the activities of the compounds have,
      accordingly, been compared on an ionic, as well as on a molecular, basis. The two
      sets of figures do not differ greatly. Trimethyl[2-(3-pyridyl)ethyl]ammonium (23)
      was the most potent compound on the chick and cat preparations. On an ionic basis
      (that is, compared with the monovalent nicotinium ion) this was 2.6 times as
      active as nicotine on the chick biventer and 11 times as active on the cat
      superior cervical ganglion. On the rat diaphragm it was 7.1 times as active as
      nicotine and less active than 1-methyl-1-(3-pyridylmethyl)-pyrrolidinium (26)
      (9.5 times the nicotinium ion) and trimethyl(4-pyridylmethyl)-ammonium (21) (11
      times). The relationships between structure and dissociation constant,
      anticholinesterase activity, and activity in the pharmacological tests have been
      discussed.

PMID- 19108161
TI  - Effects of ph on the activity of nicotine and nicotine monomethiodide on the rat
      diaphragm preparation.
AB  - Results have been obtained which substantiate the view that it is the univalent
      nicotinium ion rather than the un-ionized base which acts at the neuromuscular
      junction.

PMID- 19108162
TI  - Disposition of [s]-heparin in the rat.
AB  - [(35)S]-Heparin is rapidly taken up by tissues after intraperitoneal injection
      andrapidly degraded. Skin, aorta and lung showed an especially high affinity
      for[(35)S]-heparin. In these organs, as well as in adrenal gland, stomach, heart
      and brain,the isotope was found preponderantly as dialysable metabolite(s) of
      heparin. Another group of tissues (large intestine, fat, kidney and liver) was
      characterized by a smaller proportion of dialysable material. Tissues that showed
      a high affinity for exogenous heparin appeared to catabolize it rapidly. It is
      also noted that some of the radioactive material present in tissues after the
      injection of [(35)S]-heparin could come from the uptake of [(35)S]-sulphate
      resulting from the degradation of [(35)S]-heparin. The incorporation of [(35)S]
      sulphate into the sulphomucopolysaccharides of some tissues is recorded.

PMID- 19108163
TI  - Identification of the smooth muscle excitatory receptors for ergot alkaloids.
AB  - In cats under sodium pentobarbitone anaesthesia the first dose of ergotamine (50
      mug/kg) invariably caused retraction of the nictitating membrane and a rise of
      arterial blood pressure. However, the responses to the dose of ergotamine were
      strikingly reduced when the cats were previously treated with the adrenaline
      antagonists phenoxybenzamine (5 mg/kg) or ergotamine (50 mug/kg). Further
      experiments to identify receptors for ergotamine were carried out on three
      different isolated smooth muscle preparations: rabbit aorta, rat uterus and dog
      retractor penis.Receptors for adrenaline were selectively protected by high
      concentrations of adrenaline throughout exposure of the preparation to a blocking
      concentration of ergotamine or phenoxybenzamine. Protected muscles responded to
      ergotamine; unprotected muscles did not. Muscles where receptors for
      acetylcholine, histamine or 5-hydroxytryptamine were protected by high
      concentrations of these drugs did not respond to ergotamine. Ergometrine, which
      has no blocking action on adrenaline receptors, behaved in the same way as
      ergotamine; muscles which were protected by adrenaline against blockade by
      phenoxybenzamine responded to ergometrine, but unprotected muscles did not. The
      stimulant actions of adrenaline, ergotamine and ergometrine were also protected
      against the blocking action of phenoxybenzamine by treating the muscle with a
      high concentration of ergometrine instead of adrenaline. It is concluded that, in
      smooth muscle which can be excited by adrenaline, ergotamine and ergometrine act
      by combining with adrenaline receptors, and that ergotamine may therefore be
      regarded not only as an adrenaline antagonist but also as a partial agonist since
      it excites the same receptors.

PMID- 19108164
TI  - Spiramycin: a reappraisal of its antibacterial activity.
AB  - Spiramycin was less active than erythromycin in vitro against sensitive strains
      of Staphylococcus aureus, but was as effective against staphylococcal infections
      in mice when the drugs were administered immediately after infection: spiramycin
      was relatively more effective in prophylactic experiments when the antibiotics
      were administered at 4 or at 6 hr before infection. Strains of staphylococci
      which had been habituated to either spiramycin or erythromycin in vitro showed
      complete cross-resistance to both antibiotics in vitro, but the majority of a
      number of erythromycin-resistant strains isolated from patients were sensitive to
      spiramycin in vitro. Spiramycin was effective against a number of such strains in
      vivo, but erythromycin had little effect against these infections. Investigation
      into the distribution of the antibiotics in the serum and tissues of mice showed
      that spiramycin was maintained in tissues (lung, liver, kidney, spleen and heart)
      at higher concentrations and for a longer period than erythromycin, although
      erythromycin was initially present in serum in higher concentrations. It is
      suggested that the efficacy of spiramycin against experimental infections is due
      to its persistence in the animal body.

PMID- 19108165
TI  - Toxic effect of carbon tetrachloride on the liver cell.
AB  - Rats and mice were given injections of carbon tetrachloride into the portal vein
      or into the spleen, and the localization of the resulting hepatocellular lesions
      was studied. In contrast to some statements in the literature, and confirming
      some older reports, damage was found to be limited to the periportal areas. A
      range of changes leading to cell necrosis was found, which was frequently
      associated with pronounced vasodilatation. These features were considered to be
      evidence in favour of a direct hepatotoxic effect of carbon tetrachloride, and
      are difficult to reconcile with the view, formulated again recently by some
      workers, that carbon tetrachloride acts indirectly on the liver cell by producing
      vasoconstriction.

PMID- 19108166
TI  - Origin of the cholinergic response of the rabbit intestine to stimulation of its
      extrinsic sympathetic nerves after exposure to sympathetic blocking agents.
AB  - The effect of guanethidine and of bretylium on the response to nerve stimulation
      has been studied on two types of isolated innervated preparations of rabbit
      intestine. One preparation was that of the rabbit ileum in which the periarterial
      (mainly sympathetic) nerves were stimulated: the other was the doubly innervated
      rabbit colon where either parasympathetic (pelvic) or sympathetic (lumbar
      colonic) nerves were stimulated. In both preparations guanethidine and bretylium
      in appropriate dosage specifically blocked the inhibitory effect of sympathetic
      nerve stimulation while leaving the response to parasympathetic nerve stimulation
      and to acetylcholine unaltered: the response to noradrenaline was unaltered or
      potentiated. In the ileum, after the addition of guanethidine or of bretylium,
      the inhibitory response to periarterial nerve stimulation was replaced in every
      preparation by a motor response which had the same frequency sensitivity as
      parasympathetic nerves. In the colon a motor response to sympathetic nerve
      stimulation was rarely obtained after blocking the inhibitory response. When such
      a motor response was uncovered it had similar characteristics to the motor
      response in the ileum. Furthermore, if the parasympathetic nerves were stimulated
      for prolonged periods both the parasympathetic and sympathetic motor responses
      were reduced. These results do not support the idea that post-ganglionic
      sympathetic nerves to the intestine are generally cholinergic and are themselves
      responsible for the motor responses. The experimental results are more
      conveniently explained by assuming a mixture of cholinergic and adrenergic fibres
      in the nerves stimulated.

PMID- 19108167
TI  - Inhibition of plasma kininase activity at slightly acid ph.
AB  - Kinins, like bradykinin, are rapidly inactivated in blood and interstitial fluid
      by an enzyme called kininase. The action of this enzyme was found to be inhibited
      at slightly acid pH although the formation of kinins proceeded normally. Thus a
      slightly acid pH which is known to occur in inflamed and damaged tissue is a
      suitable environment to allow accumulation of kinins which are thought to be the
      mediators of the inflammatory response.

PMID- 19108168
TI  - Pharmacological actions of eledoisin on extravascular smooth muscle.
AB  - Some general effects and the action of eledoisin on a number of isolated smooth
      muscle preparations have been studied. It has been found that eledoisin possesses
      a potent stimulating action on all preparations of gastro-intestinal smooth
      muscle examined and also on the bronchial muscle of the guinea-pig in situ.
      Preparations of other smooth muscles were less sensitive. The rabbit colon, the
      guinea-pig ileum and, subordinately, the rabbit uterus and the frog stomach may
      be profitably used, owing to their sensitivity and the satisfactory dose/response
      relationship, for the quantitative bioassay of eledoisin in crude or pure
      preparations of the polypeptide. In parallel assays eledoisin could be easily
      distinguished from the biogenic amines and from all other known naturally
      occurring hypotensive polypeptides (bradykinins, wasp kinin, bradykinin-like
      polypeptides of the amphibian skin, physalaemin, substance P). In the
      unanaesthetized dog, subcutaneous doses of 25 to 100 mug/kg eledoisin caused a
      powerful stimulation of the motility and some secretions of the alimentary canal.
      This effect was much less pronounced in the rat and the rabbit.

PMID- 19108169
TI  - Ectopic ventricular rhythms and myocardial infarction in the domestic pig and
      their response to nialamide, a monoamine oxidase inhibitor.
AB  - The development in Indian domestic pigs of ectopic ventricular rhythms and a low
      frequency tachycardia after the two-stage ligature of the anterior descending
      branch of the left coronary artery is described. When the ligature was tied 26+/
      3 mm from the left auricular margin, the change in rhythm developed after 2 to
      2.5 hr, reached a maximum after 6 hr and persisted up to 28 hr. The
      histopathological character of the resultant acute myocardial infarction is
      presented. In all, 52 pigs were used. Pretreatment of 9 pigs, with 3 as controls,
      with a monoamine oxidase inhibitor, nialamide, 20 mg/kg daily for 2 to 4 days,
      suppressed the development of experimental ventricular arrhythmia and favourably
      influenced the ischaemic myocardium by reducing the oedema and the formation of
      microthrombi. A possible mode of action involving monoamine oxidase inhibition is
      suggested.

PMID- 19108170
TI  - Influence of metals on the activity of a bradykinin-destroying enzyme kininase.
AB  - Kininase prepared from guinea-pig serum was inhibited by cysteine at pH 7.4 to
      7.6. A similar effect was found with edetic acid. The enzyme blocked by edetic
      acid was reactivated immediately by addition of Mn(++), Co(++) and Zn(++). These
      findings indicate that kininase is a metal-activated enzyme.

PMID- 19108172
TI  - THE BRITISH PHARMACOLOGICAL SOCIETY, PROGRAMME OF MEETING, JANUARY 2 to 4.

PMID- 19108171
TI  - Cholinergic transmission in the frog spinal cord.
AB  - The effect of acetylcholine and other drugs has been tested on the isolated and
      sagittally hemisected spinal cord of the frog (Rana temporaria). The release of
      acetylcholine from this preparation during stimulation of the spinal roots and
      whole hemicord has also been studied. After inactivation of the tissue
      cholinesterases acetylcholine was released spontaneously from the preparation at
      a steady rate of about 5.5 pmole/15 min/preparation. No increase in this release
      was obtained by stimulating the dorsal roots, but antidromic stimulation of the
      ventral roots always gave an increase in the rate of acetylcholine release up to
      2.3 times the spontaneous level. Direct stimulation of the spinal cord did not
      alter the rate of acetylcholine release. Acetylcholine (1 mM) and eserine (10 mM)
      had weak excitatory actions and prolonged the reflex response of the preparation
      during dorsal root stimulation, but dihydro-beta-erythroidine and atropine had no
      effect. The response evoked by antidromic ventral root stimulation was
      potentiated by eserine (10 muM) and depressed by acetylcholine (10 muM) and
      dihydro-beta-erythroidine (1 muM) as in the toad preparation. The evidence
      supporting cholinergic transmission at some synapses in the spinal cord is
      discussed in relation to these results.

PMID- 19108173
TI  - Uptake of 5-hydroxy[14C]tryptophan by rat and dog brain slices.
AB  - Slices of rat brain take up and concentrate 5-hydroxy[(14)C]tryptophan when
      incubated at 37 degrees C in vitro. Uptake is inhibited by methyldopa and L
      phenylalanine in a competitive manner. Only a small proportion of the 5
      hydroxy[(14)C]tryptophan taken up is decarboxylated. This observation, and the
      lack of correlation between the effects of various amino-acid inhibitors on
      uptake and on decarboxylase, suggest that the two processes are not linked. In
      the cold some passive diffusion of the amino-acid occurs, as is thought to take
      place also at 37 degrees C. Experiments with dog brain show that uptake varies
      from one part of the brain to another, being greatest in the caudate nucleus. The
      possible implications of the uptake mechanism in the treatment of animals or
      patients with large doses of amino-acids are discussed.

PMID- 19108174
TI  - Relationship between structure and anticoagulant activity of coumarin
      derivatives.
AB  - Thirty-five coumarin derivatives have been examined for their anticoagulant
      activity in rabbits by determining the prothrombin time by a modification of
      Quick's onestage method, in order to find out the structural features eliciting
      the activity. The compounds include methoxylated dicoumarols, substituted 4
      hydroxycoumarins, coumarins devoid of a 4-hydroxyl group, such as 3- and 4
      phenylcoumarins and 4-methylcoumarins, and some complex coumarin derivatives
      having additional rings. The results show the complexity of the problem and the
      involvement of various factors. Among these the importance of molecular geometry
      is emphasized by the high activity of calophyllolide (31) and a new synthetic
      compound, 4-methyl-2,5-dioxo-3-phenyl-2H,5H-pyrano[3,2-c][1]-benzopyran (30). The
      importance for the anticoagulant activity of a substituent in position 8 of the
      coumarin moiety, and the role of ability to ionize with regard to the vitamin-K
      like property of some hydroxylated phenylcoumarins, are also indicated.

PMID- 19108175
TI  - The action of sodium salicylate and aspirin on some kallikrein systems.
AB  - The effects of sodium salicylate and of aspirin on the actions of pancreatic,
      salivary and serum kallikreins have been investigated. Kinin production by the
      three enzymes was assessed using a guinea-pig isolated ileum preparation. The
      esterolytic activity of pancreatic and salivary kallikreins was measured by
      determining acid release from the synthetic substrate toluene-p-sulphonyl-L
      arginine methyl ester. Sodium salicylate (up to 20 mM) or aspirin (up to 5 mM)
      failed to inhibit kinin production by each of the three enzymes. With salivary
      kallikrein, a concentration of 50 mM of sodium salicylate was required to produce
      a 50% inhibition of kinin production. No significant inhibition of esterolytic
      activity was produced by concentrations up to 5 mM of either sodium salicylate or
      aspirin. Prior incubation of sodium salcylate or aspirin with the enzymes also
      resulted in no significant effect of either drug on kinin production or
      esterolytic activity. Prior incubation of pancreatic or salivary kallikrein with
      the inhibitor from ox parotid gland (Trasylol) reduced both kinin production and
      esterolytic activity. Toluene-p-sulphonyl-L-arginine methyl ester (0.5 mM)
      inhibited kinin production by each of the three enzymes. It is concluded that
      sodium salicylate and aspirin are poor inhibitors of kallikrein activity in
      vitro.

PMID- 19108176
TI  - Observations upon roles of ether oxygen, alkyl group size, number of onium
      centres and inter-onium distance upon neuromuscular block in bis- and polyonium
      compounds.
AB  - Using the method of Van Rossum & Ariens (1959), a number of bis-, tris- and tetra
      onium neuromuscular blocking agents have been classified into depolarizing, non
      depolarizing and intermediate-acting compounds. This investigation confirmed the
      results of experiments using conventional techniques. The role of the ether
      oxygen link, the effects of inter-onium distance, alkyl group size and the number
      and nature of the onium groups were also investigated, and the reasons underlying
      the observed quantitative and qualitative differences discussed.

PMID- 19108177
TI  - Estimation of substance p in mouse brain. The identification of interfering
      nucleotides in the extract.
AB  - Substance P has been extracted from brain by previously described methods and
      assayed on the guinea-pig isolated ileum. The concentrations showed a wide
      scatter which was not due to the bioassay or to variations in the extraction
      procedure. Adenosine-5'-monophosphate and adenosine-5'-triphosphate have been
      identified in the extracts by paper chromatography and by chemical reactions. The
      concentrations of these substances were sufficient to interfere with the assay of
      substance P, adenosine-5'-monophosphate diminishing and adenosine-5'-triphosphate
      increasing the contractions of the ileum due to substance P. Adenosine-5'
      diphosphate was also detected in the extracts but its biological activity was
      insufficient to influence the estimations. The concentrations of adrenaline,
      noradrenaline, potassium ions, sodium chloride, 5-hydroxytryptamine, and gamma
      aminobutyric acid were below the threshold concentrations for interference with
      the assay of substance P.

PMID- 19108178
TI  - The effect of antidepressive drugs and some related compounds on the levels of
      adenine nucleotides, inorganic phosphate and phosphocreatine in the rat brain.
AB  - The effects upon levels of adenine nucleotides, phosphocreatine and inorganic
      phosphate of iproniazid, isoniazid, phenelzine, pheniprazine, tranylcypromine,
      harmine, imipramine, amitriptyline, orphenadrine, diphenhydramine and cocaine
      have been studied. With the exception of harmine and diphenhydramine, each of
      these compounds increased the brain level of adenosine triphosphate and, with the
      exception of imipramine and cocaine, the level of adenosine diphosphate
      decreased. Harmine had no effect on levels of adenine nucleotides and, in the
      case of diphenhydramine, the level of adenosine diphosphate increased and the
      level of adenosine triphosphate tended to decrease. There appears to be a
      relationship between the ability of the drugs to cause behavioural signs of
      central nervous stimulation and to produce an increase in the adenosine
      triphosphate/diphosphate ratio. This effect may be a factor in the action of
      antidepressive drugs.

PMID- 19108179
TI  - The action of eledoisin on the systemic arterial blood pressure of some
      experimental animals.
AB  - The blood pressure response following parenteral administration of eledoisin
      varies conspicuously from one animal species to another. In the dog the
      polypeptide elicits a clear hypotension under all experimental conditions.
      Eledoisin is active at extremely low dose levels and hypotension is not
      appreciably affected by previous treatment with atropine, sympatholytic drugs,
      ganglion-blocking agents or reserpine. Eledoisin potently antagonizes the pressor
      effects of catechol amines and of angiotensin. Longlasting hypotension can be
      obtained by intravenous infusion or subcutaneous injection of the polypeptide.
      The mechanism of action of eledoisin in the dog is believed to be chiefly
      peripheral. The rabbit, the guinea-pig and the cat behave like the dog in the
      type but not in the intensity of their blood-pressure response to eledoisin. The
      rat gives variable responses to the polypeptide. After treatment with a ganglion
      blocking drug, or in the pithed rat, a rise in blood pressure is the predominant
      effect. In the anaesthetized chicken eledoisin generally produces a diphasic
      response, but in the decapitated animal only hypertension. This last effect is
      believed to depend largely, if not entirely, on the release of catechol amines
      from body stores. The dog blood pressure may be used for the assay of eledoisin;
      suitable results may also be obtained from the pressor effects in decapitated
      chickens.

PMID- 19108180
TI  - BRITISH PHARMACOLOGICAL SOCIETY, PROGRAMME OF MEETING, JULY 10 to 12.

PMID- 19108181
TI  - THE BRITISH PHARMACOLOGICAL SOCIETY, PROGRAMME OF MEETING, JANUARY 2 to 4.

PMID- 19108182
TI  - BRITISH PHARMACOLOGICAL SOCIETY, PROGRAMME OF MEETING.

PMID- 19108184
TI  - British pharmacological society.

PMID- 19108183
TI  - The effects of some centrally acting drugs on ganglionic transmission in the cat.
AB  - Transmission through the cat superior cervical ganglion was studied by recording
      the response of the nictitating membrane to both pre- and postganglionic cervical
      sympathetic nerve stimulation. The intra-arterial injection of central depressant
      drugs to the ganglion through the lingual artery depressed transmission through
      the ganglion. The central depressant drugs tested were (in decreasing order of
      activity): amylobarbitone, pentobarbitone, carbromal, benactyzine,
      mephobarbitone, hydroxyzine, phenobarbitone, azacyclonol, methylpentynol
      carbamate, paraldehyde, phenytoin, mephenesin, chlorbutol, troxidone,
      methylpentynol and barbitone. All were weaker ganglion-blocking agents than
      tetraethylammonium. The intra-arterial injection of the central stimulant drugs
      leptazol, bemegride, amiphenazole and 5-(1,3-dimethylbut-2-enyl)-5
      ethylbarbituric acid (McN 481) also depressed ganglionic transmission. Leptazol
      or bemegride did not antagonize the ganglion-blocking action of amylobarbitone or
      troxidone. The intra-arterial injection of pecazine and perphenazine, and the
      intravenous injection of barbitone, benactyzine, azacyclonol, hydroxyzine,
      mephenesin, methylpentynol and paraldehyde impaired the response of the
      nictitating membrane to both post- and preganglionic stimulation. The
      implications of these observations are discussed.

PMID- 19108185
TI  - Effect of histamine on reproduction in female mice.

PMID- 19108186
TI  - The effect of some volatile anaesthetics on the transmurally stimulated guinea
      pig ileum.

PMID- 19108187
TI  - Effect of low temperatures on the responses of guinea-pig isolated atria to
      nicotine and to sympathetic and parasympathetic stimulation.

PMID- 19108188
TI  - The effect of sympathomimetic amines on femoral arterial blood flow in the cat.

PMID- 19108189
TI  - Receptors for catechol amines in the submaxillary glands of rats.

PMID- 19108190
TI  - A quantitative study of repeated anaphylactic reactions in isolated tissues.

PMID- 19108191
TI  - A rapid rise in blood pyruvate in cats given large doses of hydrocortisone.

PMID- 19108192
TI  - Some actions of isoprenaline and orciprenaline on perfused cat kidneys.

PMID- 19108193
TI  - A comparison of the effects of imipramine, trimipramine, and some other drugs in
      rabbits treated with a monoamine oxidase inhibitor.

PMID- 19108194
TI  - On the mechanism of action of guanethidine and bretylium.

PMID- 19108195
TI  - Some actions of tacrine on slow muscles of the toad (bufo marinus) and the chick.

PMID- 19108196
TI  - The uptake of catechol amines at high perfusion concentrations in the rat
      isolated heart: A novel catechol amine uptake process.

PMID- 19108197
TI  - The action of salicylate in reducing plasma free fatty acids and its
      pharmacological consequences.

PMID- 19108198
TI  - Actions of whole and fractionated indian cobra (naja naja) venom on skeletal
      muscle.

PMID- 19108199
TI  - The stereospecificity of nicotine.

PMID- 19108200
TI  - The stereospecificity of acetyl-alpha-methylcholine.

PMID- 19108201
TI  - The effects of four monoamine oxidase inhibitors on the rat uterus.

PMID- 19108202
TI  - Metabolic studies with certain ethyleneimine derivatives in relation to diuresis.

PMID- 19108203
TI  - The action of triethylcholine on the biological synthesis of acetylcholine.

PMID- 19108204
TI  - Distribution and excretion of [C]-neostigmine in the rat and hen.

PMID- 19108205
TI  - Potentiation of responses to noradrenaline and reversal of sympathetic nerve
      blockade in the guinea-pig vas deferens.

PMID- 19108206
TI  - The relationship between the permeability-increasing and the hypotensive
      proteases of plasma.

PMID- 19108207
TI  - Effects of mephenes in and chlorpromazine on motor nerve discharges in the
      rabbit.

PMID- 19108208
TI  - The inhibition of noradrenaline uptake by sympathomimetic amines in the rat
      isolated heart.

PMID- 19108209
TI  - The role of ionic interaction at the muscarinic receptor.

PMID- 19108210
TI  - Competitive and non-competitive inhibition of bradykinin on the guinea-pig ileum.

PMID- 19108211
TI  - Histamine release by bee venom phospholipase a and mellitin in the rat.

PMID- 19108212
TI  - Influence of some pathogenic bacteria on kinin formation and destruction.

PMID- 19108213
TI  - Antitetanus activity of central muscle relaxants.

PMID- 19108214
TI  - Conditions influencing the inhibition, by analgesic drugs, of the response to
      intraperitoneal injections of phenylbenzoquinone in mice.

PMID- 19108216
TI  - British pharmacological society.

PMID- 19108215
TI  - An analysis of the kinetics of anaesthesia of mice.

PMID- 19108217
TI  - Effect of some drugs on human umbilical artery in vitro.

PMID- 19108218
TI  - British pharmacological society.

PMID- 19108219
TI  - A comparison of the effects of ethacrynic acid and a mercurial diuretic
      (mersalyl) on sodium transport across the isolated frog skin.

PMID- 19108220
TI  - The interaction of serotonin and noradrenaline on the perfused artery.

PMID- 19108221
TI  - The effect of anticholinesterases on the increase in rate of the isolated heart
      in response to sympathetic stimulation.

PMID- 19108222
TI  - The difference in behaviour of basophil leucocytes and mast cells towards
      compound 48/80.

PMID- 19108223
TI  - Reduction of C-guanethidine levels in rat heart and diaphragm by excess calcium.

PMID- 19108224
TI  - The action of adrenaline on the ionic content and on sodium and potassium
      movements in the smooth muscle of the guinea-pig taenia coli.

PMID- 19108225
TI  - The effect of nialamide, thyroxine, reserpine and adrenalectomy on the
      sympathomimetic action of acetylcholine upon the heart.

PMID- 19108226
TI  - Kininase production by some microbes.

PMID- 19108227
TI  - The effect of propranolol on the response of the rat isolated heart to
      noradrenaline.

PMID- 19108228
TI  - Effects of d-tubocurarine and decamethonium on the central integration of somatic
      reflexes.

PMID- 19108230
TI  - The biliary excretion of neostigmine in the rat.

PMID- 19108229
TI  - The biphasic response of an isolated artery to tyramine.

PMID- 19108231
TI  - The pharmacokinetics of penamecillin.

PMID- 19108232
TI  - The formation of 5-hydroxytryptophol in brain in vitro.

PMID- 19108233
TI  - Lacrimal secretion in the cat.

PMID- 19108235
TI  - The influence of molecular weight and structure on the vascular permeability
      responses induced by glucose polymers in rat skin.

PMID- 19108234
TI  - The relationship between the penetration of tryptamine and 5-hydroxytryptamine
      into smooth muscle and the associated contractions.

PMID- 19108236
TI  - Some data on two purified kininogens from human plasma.

PMID- 19108237
TI  - Role of catecholamines and the chemoreceptor trigger zone in reserpine induced
      emesis.

PMID- 19108238
TI  - Intracarotid injections and infusions of cholinomimetic drugs and their
      antagonists in conscious dogs.

PMID- 19108239
TI  - Role of hageman factor in the activation of guinea-pig pre-kallikrein.

PMID- 19108240
TI  - Occurrence of dopamine and noradrenaline in the nervous tissue of some
      invertebrate species.

PMID- 19108241
TI  - The central stimulant properties of some substituted indolylalkylamines and beta
      carbolines and their activities as inhibitors of monoamine oxidase and the uptake
      of 5-hydroxytryptamine.

PMID- 19108243
TI  - Possible role of lecithin in the development of the slow muscle contracting
      activity of human plasma.

PMID- 19108242
TI  - Modification of pressor effects of some vasoactive polypeptides in the rat by
      guanethidine propranolol and related agents.

PMID- 19108244
TI  - The action of barbitone on aerobacter aerogenes (klebsiella aerogenes).

PMID- 19108246
TI  - British pharmacological society.

PMID- 19108245
TI  - Effect of reserpine and monoamine oxidase inhibition on the uptake and
      subcellular distribution of h-noradrenaline.

PMID- 19108247
TI  - Factors influencing the action of morphine on acetylcholine release in the guinea
      pig intestine.

PMID- 19108248
TI  - British pharmacological society.

PMID- 19108249
TI  - An analysis of the responses of the isolated portal vein of the rabbit to
      electrical stimulation and to drugs.

PMID- 19108250
TI  - A study of the role of brain catecholamines in drug induced tremor.

PMID- 19108251
TI  - Antiviral activity of sodium fusidate and related compounds.

PMID- 19108252
TI  - The effect of depolarization on the rate constants of the hyoscine-acetylcholine
      antagonism studied on the longitudinal muscle of the guinea-pig's ileum.

PMID- 19108253
TI  - The action of angiotensin II on guinea-pig ileum and its modification by changes
      in sodium concentration.

PMID- 19108254
TI  - Disposition of h-epsilon amino caproic acid and its interaction with adrenergic
      neurones.

PMID- 19108255
TI  - Intramural nerves in the ventricular myocardium of the domestic fowl and other
      animals.

PMID- 19108256
TI  - Actions of sodium ascorbate on smooth muscle.

PMID- 19108257
TI  - Effects of cocaine and of monoamine oxidase and catechol-o-methyl transferase
      inhibitors on transmission to the guinea-pig vas deferens.

PMID- 19108258
TI  - Effect of sympathomimetic and allied amines on temperature and oxygen consumption
      in chickens.

PMID- 19108259
TI  - Comparison of isotopic and non-isotopic methods of estimating histidine
      decarboxylase activity.

PMID- 19108260
TI  - The analysis of the inhibitory effect of anaesthetics and propranolol on adreno
      medullary secretion evoked by calcium or acetylcholine.

PMID- 19108261
TI  - The importance of plasma kinins in the anaphylactoid reaction in rats.

PMID- 19108262
TI  - Some effects of hexafluorobenzene in cats.

PMID- 19108264
TI  - Contributions by title only.

PMID- 19108263
TI  - The effect of ambient temperature on the actions of tremorine on body temperature
      and on the concentration of noradrenaline, dopamine, 5-hydroxytryptamine and
      acetylcholine in rat brain.

PMID- 19108265
TI  - Training and employment in pharmacology. Fourth updating survey on the
      organisation of pharmacology in Great Britain: summary of findings.

PMID- 19108267
TI  - Contributions by title only.

PMID- 19108266
TI  - Evidence for a 5-HT(1)-like receptor mediating the amplifying action of 5-HT in
      the rabbit ear artery.
AB  - 1 The nature of the 5-hydroxytryptamine (5-HT) receptors which amplify the
      vasoconstrictor effect of methoxamine was examined in the rabbit isolated
      perfused ear artery with intact endothelium. Indices of amplification were
      leftward shifts of methoxamine dose-response (DR) curves produced by 5-HT (0.3
      muM) (Method I), and the appearance of vasoconstrictor responses to 5-HT receptor
      agonists when methoxamine was present in a near-threshold concentration (Method
      II).2 The amplifying effect of 5-HT (Method I) was unaffected by prazosin (0.08
      muM), was partly depressed by 5-HT(2)-receptor antagonists in high concentrations
      (ketanserin 0.5 muM, LY53857, 1.0 muM), and was abolished by a non-selective
      antagonist of 5-HT(1) and 5-HT(2) receptors (methiothepin, 0.01 muM).3 Amplifying
      potencies of agonists assessed by both Methods I and II were in the order 5
      carboxamidotryptamine (5-CT)>5-HT>alpha-methyl 5-HT. The potency of sumatriptan
      (assessed by Method II only) was intermediate between those of 5-HT and alpha
      methyl 5-HT.4 Ketanserin and LY53857 inhibited the amplifying action of 5-CT to
      about the same extent as that of 5-HT.5 The amplifying potencies of the agonists
      are in marked contrast to the reported contractile potencies in the rabbit aorta
      where the receptor is 5-HT(2), but are almost identical with reported contractile
      potencies in the dog saphenous vein where the receptor is 5-HT(1)-like.6 It is
      concluded that a 5-HT(1)-like receptor mediates the amplifying interaction
      between 5-HT and methoxamine in the rabbit ear artery which can be weakly blocked
      by ketanserin and LY53857.7 Since 5-CT was equipotent when applied separately to
      the intimal and adventitial surfaces of the artery, it is suggested that the 5
      HT(1)-like receptors are distributed uniformly across the artery wall.

PMID- 19108268
TI  - Contributions by title only.

PMID- 19108270
TI  - Demonstrations.

PMID- 19108272
TI  - Contributions by title only.

PMID- 19108273
TI  - Publication by title only.

PMID- 19108274
TI  - 50 years of the british journal of pharmacology.

PMID- 19108275
TI  - Contributions by title only.

PMID- 19108269
TI  - Poster communications.

PMID- 19108271
TI  - Poster communications.

PMID- 19108276
TI  - Published by title only.

PMID- 19108277
TI  - The distribution of tritium-labelled prostaglandin E(1) injected in amounts
      sufficient to produce central nervous effects in cats and chicks.
AB  - 1. After injection of tritiated prostaglandin E(1) into the lateral cerebral
      ventricle, the carotid and vertebral arteries and the aorta in cats, only a small
      proportion of the radioactivity was recovered from the central nervous system.2.
      Similar results were obtained when the prostaglandin was given intra-venously and
      intra-arterially to chicks.3. The results of this study confirm work in other
      species (Hansson & Samuelsson, 1965; Samuelsson, 1964, 1965) and suggest that
      prostaglandin E(1) exerts its central pharmacological actions in small
      concentrations.

PMID- 19108280
TI  - Selective vasoconstrictor effect of atropine on the parametrial arteries in the
      pregnant guinea-pig (T).

PMID- 19108278
TI  - The biological properties of the optical isomers of propranolol and their effects
      on cardiac arrhythmias.
AB  - 1. The optical isomers of propranolol have been compared for their beta-blocking
      and antiarrhythmic activities.2. In blocking the positive inotropic and
      chronotropic responses to isoprenaline, (+)-propranolol had less than one
      hundredth the potency of (-)-propranolol. At dose levels of (+)-propranolol which
      attenuated the responses to isoprenaline, there was a significant prolongation of
      the PR interval of the electrocardiogram.3. The metabolic responses to
      isoprenaline in dogs (an increase in circulating glucose, lactate and free fatty
      acids) were all blocked by (-)-propranolol. (+)-Propranolol had no effect on
      fatty acid mobilization but significantly reduced the increments in both lactate
      and glucose.4. Both isomers of propranolol possessed similar depressant potency
      on isolated atrial muscle taken from guinea-pigs.5. The isomers of propranolol
      exhibited similar local anaesthetic potencies on an isolated frog nerve
      preparation at a level approximately three times that of procaine. The racemic
      compound was significantly less potent than either isomer.6. Both isomers of
      propranolol were capable of preventing adrenaline-induced cardiac arrhythmias in
      cats anaesthetized with halothane, but the mean dose of (-)-propranolol was
      0.09+/-0.02 mg/kg whereas that of (+)-propranolol was 4.2+/-1.2 mg/kg. At the
      effective dose level of (+)-propranolol there was a significant prolongation of
      the PR interval of the electrocardiogram. Blockade of arrhythmias with both
      isomers was surmountable by increasing the dose of adrenaline.7. Both isomers of
      propranolol were also capable of reversing ventricular tachycardia caused by
      ouabain in anaesthetized cats and dogs. The dose of (-)-propranolol was
      significantly smaller than that of (+)-propranolol in both species but much
      higher than that required to produce evidence of beta-blockade.8. The
      implications of these results are discussed.

PMID- 19108279
TI  - The action of acetylcholine and other drugs on the efflux of potassium and
      rubidium from smooth muscle of the guinea-pig intestine.
AB  - 1. A method is described for measuring continuously the efflux of potassium or
      rubidium from smooth muscle of the guinea-pig.2. Muscarinic drugs cause at
      maximum a 100-fold increase in the efflux rate, due to a direct increase in
      permeability and only to a minor extent secondary to depolarization. With
      acetylcholine the dose response curve for producing efflux is displaced to 1,000
      times higher concentrations than that for contraction.3. The shift varies with
      different agonists. The efflux and contractile responses to agonists are
      antagonized to an equivalent extent by atropine and several other reversible
      antagonists but benzhexol has a relatively greater effect on efflux. An estimate
      of spare receptors was obtained with benzilylcholine mustard and was similar for
      both responses. Dibenamine and local anaesthetics led to a parallel shift of the
      contraction dose response curve but a depression without shift in the efflux
      response.4. The most satisfactory explanation of these results is that there are
      two types of the muscarinic receptor in the smooth muscle of the guinea-pig
      intestine.

PMID- 19108281
TI  - Paracetamol metabolism and excretion in paracetamol overdosage complicated by
      hepatic necrosis (T).

PMID- 19108282
TI  - Computer programme to process liquid scintillation counting data (T).

PMID- 19108283
TI  - A controlled environment chamber (T).

PMID- 19108284
TI  - Pharmacology of chlorpromazine: Relevance to clinical studies, of investigations
      of absorption, distribution and metabolism in animals (T).

PMID- 19108285
TI  - Pharmacology of chlorpromazine: analysis, concentrations in plasma in man, and
      excretion of metabolites in man (T).

PMID- 19108287
TI  - Clinical interviews with drug abusers (T).

PMID- 19108286
TI  - alpha-Adrenoceptor mediation of central hyperthermic responses to noradrenaline
      in rabbits (T).

PMID- 19108288
TI  - Automatic programme control for Skinner box experiments (T).

PMID- 19108289
TI  - Histochemical fluorescence studies on the human fallopian tube (T).

PMID- 19108290
TI  - Simplified extraction, chromatography and bioassay of prostaglandins in
      biological extracts (T).

PMID- 19108291
TI  - A simple system allowing repeated intravenous injection in the conscious rat (T).

PMID- 19108292
TI  - Effect of magnesium ions on drug-induced contractions of vascular smooth muscle
      (T).

PMID- 19108295
TI  - Some effects of corticosteroids in relation to hepatoxicity (T).

PMID- 19108294
TI  - An inexpensive rat holder for blood pressure recording in the conscious animal
      (T).

PMID- 19108293
TI  - The use of a feed-back classroom in pharmacology teaching (T).

PMID- 19108296
TI  - Fourth gaddum memorial lecture, school of pharmacy, university of london, january
      1973.

PMID- 19108297
TI  - Hypothermic effect of sodium acetysalicylate on afebrile monkeys.
AB  - 1 Afebrile monkeys (Macaca cyclopis) receiving systemic (100-300 mg/kg, i.p.) or
      central (5-20 mg into the 3rd cerebral ventricle) administration of sodium
      acetylsalicylate showed a dose-dependent reduction in rectal temperature in a
      thermoneutral environment (25 degrees C).2 Administration of sodium
      acetylsalicylate (10 mg) into the 3rd cerebral ventricle produced a hypothermia
      with a temperature decrement of 1.0 degrees C, ehile an intraperitoneal injection
      of 300 mg/kg was required for a temperature decrement of 0.9 degrees C. The ratio
      between the total doses given by the two toutes was 1 to 120.3 Following the
      administration of sodium acetylsalicylate, a decline in rectal temperature was
      accompanied by a tail cutaneous vasodilatation.4 The data suggest that sodium
      acetylsalicylate can lower the normal body temperature by activating heat loss or
      decreasing the normal (tonic) inhibition of the heat loss mechanism via the
      central nervous system.

PMID- 19108298
TI  - Effect of vinblastine and mustine on the distribution of T and B-lymphocytes.

PMID- 19108299
TI  - The relative inducing potency of antiepileptic drugs in mice.

PMID- 19108300
TI  - Methods for the Histopathological study of the drug-damaged guinea-pig organ of
      Corti.

PMID- 19108301
TI  - Hay Fever: Diagnosis and treatment with vitamin C.

PMID- 19108303
TI  - 5-Fluorouracil-induced thiamin deficiency-an experimental study.

PMID- 19108302
TI  - Demonstration of central synaptic effects of chemicals in the American cockroach.

PMID- 19108304
TI  - Vitamin C in the plasma and in the leukocytes of Italians in different periods of
      the year.

PMID- 19108306
TI  - The effects of autonomic drugs in mice.

PMID- 19108305
TI  - Diuretic testing.

PMID- 19108307
TI  - Laboratory demonstration of drug responses using the videograph recording system.

PMID- 19108308
TI  - Audio-visual teaching material used on courses for new Home Office Licensees.

PMID- 19108309
TI  - Demonstrations.

PMID- 19108310
TI  - Contributions by title only.

PMID- 19108311
TI  - Contributions by title only.

PMID- 19108312
TI  - Contributions by title only.

PMID- 19108313
TI  - Contributions by title only.

PMID- 19108314
TI  - Contribution by title only.

PMID- 19108315
TI  - Contributions by title only.

PMID- 19108317
TI  - Contribution by title only.

PMID- 19108316
TI  - Introduction to the 9th international congress of pharmacology issue.

PMID- 19108318
TI  - Contributions by title only.

PMID- 19108319
TI  - Contributions by title only.

PMID- 19108321
TI  - Contributions by title only.

PMID- 19108320
TI  - Contributions by title only.

PMID- 19108323
TI  - Foreword to the first issue of Br. J. Pharmac. Chemother.

PMID- 19108322
TI  - Editorial.

PMID- 19108324
TI  - An appreciation of Dr Raymond Ing F.R.S., Founding Secretary of the British
      Journal of Pharmacology.

PMID- 19108325
TI  - Contributions by title only.

PMID- 19108326
TI  - Contributions by title only.

PMID- 19108328
TI  - Contributions by title only.

PMID- 19108327
TI  - Contributions by title only.

PMID- 19108329
TI  - Contributions by title only.

PMID- 19108330
TI  - Contributions by title only.

PMID- 19108331
TI  - Contributions by title only.

PMID- 19108332
TI  - The consequences of success.

PMID- 19108333
TI  - Contributions by title only.

PMID- 19108334
TI  - Contributions by title only.

PMID- 19108335
TI  - Contributions by title only.

PMID- 19108337
TI  - Contribution by title only.

PMID- 19108336
TI  - Endothelium-derived relaxing factor is an endogenous vasodilator in man.
AB  - Removal of venous endothelium in man leads to vasoconstriction and loss of
      dilator response to acetylcholine but not to glyceryl trinitrate. This pattern of
      responses can be accounted for by loss of endothelium-derived relaxing factor
      (EDRF), but not by loss of prostacyclin. This provides the first direct evidence
      for endothelium-dependent dilatation in man in vivo, and suggests that basal
      release of EDRF is a determinant of resting venous tone.

PMID- 19108338
TI  - Communications by title only.

PMID- 19108339
TI  - The diagnosis of art: Sir George  Savile, 8th Baronet--the ears  have it?

PMID- 19108340
TI  - [Role of the methodology in cluster randomized trials].

PMID- 19108342
TI  - [Cancer excision margins].

PMID- 19108341
TI  - Care for health cannot be limited to one country or one town only, it must extend
      to entire world: role of Andrija Stampar in building the World Health
      Organization.

PMID- 19108344
TI  - [The ethnic structure of the population of Polog at the end of the 19th century,
      1896-1900].

PMID- 19108345
TI  - The librarian as a teacher: experiences from a problem-based setting.

PMID- 19108346
TI  - National electronic Library for Health: progress and prospects.

PMID- 19108347
TI  - The impact of health information delivery on the quality of patient care: whither
      medical information science?

PMID- 19108348
TI  - Current access to health information in Zambia: a survey of selected health
      institutions.
AB  - OBJECTIVE: To assess the current situation of access to information by health
      staff at selected central, provincial, district hospitals and health centres in
      Zambia. METHODS: Government and non-governmental institutions were visited in the
      Lusaka Urban District and nine rural districts in the North-Western, Western and
      Central Provinces of Zambia in 2001. Thirty interviews were held with provincial
      and district health directors, medical doctors, nurses and clinical officers in
      district hospitals and rural and urban health centres. In 2006, a follow-up visit
      was undertaken to the health centres in the Lusaka Urban District in Lusaka
      Province and the Sesheke District in the Western Province. RESULTS: There is
      limited access to health information for health workers in Zambia. In hospitals
      and health centres, where there is access, it is usually provided in an ad hoc
      manner without a central policy from the government. In all the places visited,
      there was also an overwhelming expressed need for different types of information
      relating to the professional or personal needs of health care workers.
      CONCLUSIONS: The study found that access to information was very poor. There were
      some excellent examples of local initiatives showing that, even under difficult
      financial and infrastructural circumstances, it was feasible to improve health
      workers' access to information by using low technology, information access
      initiatives. These existing local initiatives deserve to be scaled up, while new
      initiatives should be adopted to improve access to information in a much more
      structured way. Of paramount importance is the formulation and implementation of
      an information policy that will guarantee the provision of health information to
      Zambian health workers.

PMID- 19108351
TI  - Safely implementing health information and converging technologies.

PMID- 19108352
TI  - [Reflections on the European "system" of kinship and marriage].

PMID- 19108353
TI  - [Grain free trade and representations of space during the early-19th-century
      French subsistence crisis].

PMID- 19108354
TI  - [The monarchic state and the family, 16th-18th centuries].

PMID- 19108355
TI  - Response to "Deception and the principle of double effect" by Amnon Goldworth (CQ
      Vol. 17, No. 4). The role of intention.

PMID- 19108356
TI  - The right's reasons: constitutional conflict and the spread of woman-protective
      antiabortion argument.

PMID- 19108357
TI  - In defense of Prometheus: some ethical, economic, and regulatory issues of sports
      doping.

PMID- 19108358
TI  - The problem of doping.

PMID- 19108360
TI  - Journal of Integrative Neuroscience.

PMID- 19108359
TI  - [Cytoskeleton of prokaryote--introduction].

PMID- 19108361
TI  - [Spine instability and its means of management].

PMID- 19108362
TI  - [An invitro biomechanical study of treatment for lumbar spondylolithesis using
      nail-grooved tail steel plate and intervertebral implant (Wendeng Fusion Cage,
      WDFC)].
AB  - OBJECTIVE: To evaluate the biomechanics of treatment for lumbar spondlolisthesis
      using nail-grooved tail steel plate and WDFC (Wendeng Fusion Cage) implant.
      METHODS: There were nine permanent waist-sacrum wet bone (L3-S3) in 1 to 2 clay
      cold hours including 6 men and 3 women. They were seldom separated into 3 groups,
      which were fixed by nail-grooved fail plus WDFC. The model was separate into two
      kinds for single and across. With electrometry, deal experiment date with
      Graftool software. Each piece should be tested twice respectively. RESULTS: The
      single and across segment non-destructive compression experiment. No-mid
      compression from 0 to 750 N,the related coefficient and curves had no obvious
      change on inclined rate. In the single segment curvedly serial experiment, the
      stress at all point measured by two sides steel plate-was mostly linear growth.
      In the across segment curvedly serial experiment, the inclined rate become big
      and appear anisomerous. CONCLUSION: It's proved by biomechanics that the steel
      plates with single furrow and cylinder wing plus WDFC has a good stability to
      cure lumbar vertebra slips.

PMID- 19108363
TI  - [Anti-rotation biomechanical study of wire and various cable system in the
      posterior brooks instrumentation for atlantoaxial instability].
AB  - OBJECTIVE: To compare the anti-rotation biomechanical performances of wire and
      various cable fixation devices currently used in the posterior Brooks
      instrumentation for atlantoaxial instability. METHODS: In this experiment,six
      specimens of the atlantoaxial complex (Occipital-C3) were used. The models of the
      normal complex,unstable complex (type II odontoid fracture) and fixed complex
      were established. On the WD-5 mechanics experimental machine,the parameters
      including the strength and rigidity of anti-rotation were quantified for the
      normal complex (group N),the atlantoaxial instability complex (group M), the new
      type Titanium cable (group A), Atlas titanium cable (group B), Songer Titanium
      cable (group C), stainless wire(group D). RESULTS: The max strength of A, B, C, D
      groups was 12.5, 11.3, 11.52, 11.55 N x m respectively, the max rigidity was
      58.81, 53.17, 54.11, 54.35 N x cm/deg respectively. The strength and rigidity of
      anti-rotation, compare to the unstable atlantoaxial complex which were fixed by
      the new double locking Titanium cable fixation system were superior to those of
      normal complex, instability complex, Songer or Atlas Titanium cable (P < 0.05).
      CONCLUSION: Having been changed the locking method, the anti-rotation
      biomechanical characteristics of the new type double locking Titanium cable
      fixation system are superior or similar to the traditional Songer or Atlas
      Titanium cable.

PMID- 19108364
TI  - [Clinical observation of the elbow joint function after shortening fixation of
      the comminuted olecranon fractures].

PMID- 19108365
TI  - [Biomechanical test of the general spinal pedicle screw-rod orthopaedics fixation
      system in the treatment of diseases related to spinal instability].
AB  - OBJECTIVE: To evaluate the biomechanical performance of the spinal universal
      fixation system(GSPS) in treating the diseases related to spinal instability.
      METHODS: Four instable models and 4 fracture models were made of fresh pig's
      thoracolumbar specimens (T10-L3). Self-designed GSPS were used in the simulated
      operation. Axial loading test and torsion test were made. The stress-strain
      relation of the GSPS was observed. The extracting force of link bar from elastic
      jig was tested. RESULTS: The strain value of each tested point changed linearly
      when the axial load changed from 0 to 600 N. There was linear relation between
      the torsion and the torsion angle. The latter was less than 6 degrees when the
      former reached 300 N x cm. The minimum extracting force of the link bar from the
      elastic jig was more than 3 300 N. CONCLUSION: The GSPS has high energy and high
      elasticity on anti-axial and anti-torsion load. It is stable to use elastic link
      bar.

PMID- 19108366
TI  - [A biomechanical evaluation of the sacroiliac anatomy type bar-plate internal
      fixation system].
AB  - OBJECTIVE: To evaluate the biomechanical personality of the sacroiliac anatomy
      type Bar-plate system (SABP), which was of fixation usage to the fracture or
      dislocation of the sacroliliac joint. METHODS: Twenty fresh and freeze cadaver
      pelvises were prepared with pelvic fracture model,compared with different
      internal fixation systems such as Galveston technique, transiliac rod fixation,
      reconstruction plate and sacroiliac joint screws using experimental stress
      analysis methods,and then the stability of the pelvic was obtained and evaluated.
      RESULTS: Using new SABP system to treat pelvic sacroiliac joint fracture and
      dislocation was higher 10%, 11%, 16%, 21% in the strength; more 12%, 14%, 21%,
      31% in rigidity; less 13%, 14%, 22%, 25% in straining;less 10%, 12%, 16%, 20% in
      shifting than the Galveston technique, transiliac rod fixation, reconstruction
      plate and sacroiliac joint screws, with remarkable statistic difference (P <
      0.05), and it was even better than cadaver pelvis. CONCLUSION: To treat pelvic
      facture, the fixation with new SABP system is of better strength, rigidity and
      stability, and the SABP system is an ideal new application.

PMID- 19108367
TI  - [The feasibilty study of posterior laminar screw fixation techniques in axis].
AB  - OBJECTIVE: Observation and measurement were done on axial laminar to get the
      parameters of morphology in Chinese. To evaluate the possibility of the placement
      of axial laminar screw. METHODS: The relative parameters of 28 sets of fresh
      Chinese adults' axial specimens were measured with a digital caliper, a
      goniometer and imageology, including the distance from superior and inferior the
      anchor point of the axial laminar screw to superior margin of the axial laminar,
      the superior,middle and inferior thickness of axial laminar, the height of axial
      laminar, the length and the angle of the axial laminar screw trajectory, the
      distance from the anchor point of the axial laminar screw to hole of vertebral
      artery and the central point of inferior articular process and so on. The data
      were statistically analyzed. RESULTS: The distance from superior and inferior the
      anchoi point of the axial laminar screw to superior margin of the axial laminar
      was 4 mm and 8 mm respectively. The superior, middle and inferior thickness of
      axial laminar was 3.2, 6.7, 5.5 mm respectively. The height of axial laminar was
      12.8 mm. The superior and inferior length of axial laminar screw trajectory was
      26.2 mm and 25.5 mm respectively. CONCLUSION: It is feasible and reliable for
      posterior laminar screw fixation techniques of axis in Chinese. C2 laminar screw
      fixation techniques could be used as a supplementary method for conventional
      posterior screw fixation techniques of C2.

PMID- 19108368
TI  - [Comparison of treatment effect of degenerative lumbar instability with
      transpedicular screw fixation combined with the posterior lumbar interbody fusion
      with cage and conservative treatment].

PMID- 19108369
TI  - [Treatment of lumbar spondylolisthesis by posterior restoration and three-column
      fixation].
AB  - OBJECTIVE: To investigate the late results of using posterior restoration and
      three-column fixation to treat lumbar spondylolisthesis. METHODS: One hundred and
      eighty-four patients with lumbar spondylolisthesis were collected from March 1999
      to May 2007, they were treated by posterior restoration and fixation with single
      nail-grooved tail steel plate and fixed with cage (WDFC). Among these cases, 87
      cases were fixed with one WDFC, 97 cases were used two WDFCs. RESULTS: All
      patients were followed up for 8 to 69 months(averaged 23 months). According to
      Nakai standard, the results was excellent in 142 cases, good in 34, fair in 8,
      the excellent and good rates were 95.6%. Seventy-nine vertebraes with I degree
      spondylolisthesis were reduced after surgery. Eighty-seven vertebraes with II
      degree spondylolisthesis were reduced except 9 with I degree spondylolisthesis
      left. Twenty-one with III degree spondylolisthesis were reduced except 5 with I
      degree spondylolisthesis left; In 2 with IV degree spondylolisthesis, one with I
      degree spondylolisthesis left and the other with II degree spondylolisthesis
      left. The follow-up results showed that there was no statistical significance in
      the height of intervertebral space between preoperation and post-operation, and
      no recurrence was observed and no single nail-grooved tail steel plate and WDFC
      were loose or crashed. CONCLUSION: Posterior restoration and three-column
      fixation is a positive modus operandi to treat lumbar spondylolisthesis,which can
      reduce excellently,keep the height of intervertebral space and stabilization of
      segment, obtain high rate of fusion, and cut down complication.

PMID- 19108370
TI  - [Causes of bad outcomes of intra-articular calcaneal fractures after surgical
      treatment].

PMID- 19108371
TI  - [Clinical curative effect of the treatment of the disease of vertebral column by
      the arc-track private lock pedicle orthopaedics fixation system (ALPF II)].
AB  - OBJECTIVE: To approach the clinical curative effect of treatment of the disease
      of vertebral column by the arc-track private lock pedicle orthopedics fixation
      system (ALPF II). METHODS: Eighty-six cases were treated by useing ALPF II. The
      average age of the cases was 36.8 years (range from 18 to 69 years),the male was
      39 cases and the female was 37 cases. The results were evaluated and all the
      cases were followed-up. RESULTS: All the patients were followed-up for 9 to 30
      months. The amelioration of patients nerve function,spinal motion, low back pain
      and leg pain was 94.1%, 65.9%, 92.1% and 87.4% respectively. The height of
      anterior and posterior border after operation were improved greatly than that
      before operation (P < 0.01, P < 0.05). The X-ray films showed that the angle of
      kyphosis was also improved significantly (P < 0.01). CONCLUSION: To treat spinal
      column disease, ALPF II is a kind of operation safety simple, easy control, reset
      good, curative effect credibility, the complications little of treatment method.

PMID- 19108372
TI  - [Early treatment for the unstable fracture of the thoracolumbar].
AB  - OBJECTIVE: To research the efficacy and feasibility for unstable fracture of
      thoracolumbar with AF spine internal fixation device. METHODS: Thirty-two
      patients with unstable fractures of T11-L3 were treated with AF spine internal
      fixation device and autograft between vertebral lamina vertebral body transverse
      process from January 2002 to June 2006. There were 21 female and 11 male, aging
      from 58 to 72 years with a mean of 62 years. All these patients were examined
      with x-ray and CT preoperative and postoperative respectively. They were followed
      up thirteen months averagely, observing the stability of spinal column, bone
      grafting fusion, the height of vertebra and recovery of anterior bone fragment
      herniation. RESULTS: All these AF spine internal fixation devices treated for the
      unstable fractures of thoracolumbar had not removed because of internal fixation
      failure or pain. Fracture healing and grafting fusion appeared after operation
      three months averagely. X-rays revealed post-protrusion angle were recovered from
      22 degrees to 8.5 degrees, the heights of anterior were recovered from 50% to
      86%, the angle of posterior were recovered from 94% to 98%. The postoperative CT
      scan showed that six cases with herniation to canal gained a completely
      recoveries. CONCLUSION: AF spine internal fixation device used in early stage for
      unstable fracture of thoracolumbar is a simple and effective method. It has
      advantages such as providing early substantial fixation, maintaining a well three
      column stability. Bone grafting is a key factor in this operative technique.

PMID- 19108373
TI  - [Clinical observation on the treatment of tibiofibular fracture with calcaneus
      traction combined with small splint fixation].

PMID- 19108374
TI  - [Repair and re-establishment to traumatic upper cervical instability].
AB  - OBJECTIVE: To summarize and analyze the therapeutic effect of traumatic upper
      cervical instability and investigate therapeutic methods and effect. METHODS:
      There were 19 patients with traumatic upper cervical instability (male 16, female
      3), aged from 21 to 56 years,included 3 cases of atlas fracture, 10 cases of dens
      fracture, 3 cases of axis pedicle fracture, 3 cases of atlanto-axial subluxation.
      Among them, 6 cases included 1 case of dens fracture, 1 case of dens fracture
      affiliated with atlas fracture, 1 case of axis pedicle fracture, 3 cases of
      atlanto-axial subluxation were treated conservatively and the other 13 cases were
      treated by operations. RESULTS: Nineteen cases were followed up for 1.8 years in
      average (6 months to 6 years). According to JOA standard for evaluation, the rate
      of improvement was 42.5% and 87.0% for conservative treatment and operation
      respectively. CONCLUSION: Traumatic super cervical unsteadiness should be
      diagnosed and treated early. Under the condition of upper cervical vertebra being
      completely fixed,the function of cervical vertebra to maximum extent could be
      reserved when choosing operation method. Especially, the precise fusion of upper
      cervical vertebra plays a vital role of long-term efficacy.

PMID- 19108375
TI  - [Clinical therapeutic effect observation of using the modified reconstruction of
      spinous processes for treating cervical vertebrae degenerative disease].
AB  - OBJECTIVE: To report clinical application and therapeutic effect on the modified
      reconstruction of spinous processes for treating cervical vertebrae degenerative
      disease. METHODS: Twenty-nine cases with cervical vertebrae degenerative disease
      were treated with the modified reconstruction of spinous processes. Among them,
      21 cases were male and 8 cases were female. The age was from 37 to 76 years with
      an average age of 55 years. Of them, 4 cases occured immediately with no factors,
      15 cases occured chronically, and 10 cases occured following substantial trauma.
      The last-time of disease was 5 h to 25 years, with an average of 1 year and 8
      months. RESULTS: After 3 months to 5 years and 6 months followed-up, the results
      were excellent in 18 cases (recovery rate >75%), good in 7 cases (recovery rate
      50% to 75%), fair in 3 cases (recovery rate 25% to 49%), poor in 1 case (recovery
      rate < or =24%)with average recovery rate 86.6% according to JOA 17 score system.
      CONCLUSION: The reconstruction of spinous processes may be an effective measure
      in spinal decompression absolutely, meanwhile, it can maintain the spinal
      sequences stable, also can avoid or reduce the axial symptoms and the correction
      of cervical kyphosis.

PMID- 19108376
TI  - [Clinical study on multi-segmental pedicle screw implantation in the treatment of
      middle-upper thoracic spine fracture and dislocation].
AB  - OBJECTIVE: To review a group of clinical data of pedicle screw implantation in
      the treatment of middle-upper thoracic fracture and dislocation and explore these
      clinical effect. METHODS: Through the retrospective analysis of 23 patients (31
      vertebraes) of middle-upper thoracic fracture and dislocation included 21 male
      and 2 female,aged from 20 to 47 years in average of 33.5 years. The location and
      type of fractures were as follows: 2 in T2, 2 in T3, 5 in T4, 6 in T5, 10 in T6,
      4 in T7, 2 in T8. Three cases were compression fractures, 7 burst fractures, 9
      fracture-dislocations, 4 burst-dislocations. RESULTS: After a followed-up from 3
      to 48 months, average 25.5 months, all cases had no serious complications.
      Anterior height of affected vertebral bodies had been restored from 40.4% to
      90.3% after operation. Patients with incomplete spinal cord injuries improved one
      to two grades according to ASIA grade of spinal cord injury. Patients with
      complete spinal cord injuries improved 21.7 scores on average according to
      Sensory and Motion Scores. CONCLUSION: Multi-segmental pedicle screw implantation
      for the injuries of vertebral body may get satisfactory reduction and fixation
      effects, and prevent the long-term loss of the vertebral body height and
      implanting failure.

PMID- 19108377
TI  - [Clinical application of the reconstruction of prevertebral fascia in cervical
      vertebrae anterior approach].
AB  - OBJECTIVE: To evaluate the preventive effect of the reconstruction of
      prevertebral fascia on the complication of cervical vertebrae anterior approach.
      METHODS: One hundred and seventy-six patients with cervical vertebrae anterior
      approach were divided into two groups by throwing coins, coins for the positive,
      patients entered the group A, coins for the negative, patients entered the group
      B. Eighty-seven cases of group B were treated with cervical vertebrae anterior
      decompression, bone grafting and internal fixation with plate and screws. In
      other 89 cases of group A, prevertebral fascia were covered on the surface of the
      plate and screws as experiment group. The patients were followed up after three
      weeks, three months and 12 months. The incidence of the dysphagia was as
      observation indicator and was statistically analyzed. RESULTS: The followed-up
      period was 3 weeks, 3 months and 12 months after operation. The incidence of the
      dysphagia of group A was respectively 25.8%, 9.0%, 5.6%; the incidence of the
      dysphagia of group B was respectively 25.3%, 20.6%, 14.9%. The dysphagia in the
      experiment group was lower than that in contrast group, 3 months and 12 months
      after operation (3 months P = 0.030, 12 months P = 0.049 < 0.05). CONCLUSION: The
      reconstruction of prevertebral fascia is an effective method to avoid the
      dysphagia of cervical vertebrae anterior approach.

PMID- 19108378
TI  - [Therapeutic effects of microendoscopic discectomy (MED) for the treatment of
      lumbar disc herniation with a follow-up].
AB  - OBJECTIVE: To evaluate mid-term clinical results of microendoscopic discectomy
      (MED) for the treatment of lumbar disc hermiation. METHODS: In the study, 117
      patients were reviewed,including 63 male and 54 female, ranging in age from 24 to
      72 years,with an average of 50.6 years. Among the patients, 60 patients had
      simple lumbar disc herniation, 10 patients had simple lateral crypt stenosis, 32
      patients had lumbar disc herniation combined with lateral crypt stenosis, and 15
      patients were combined with calcified nucleus pulposus. Two patients had
      herniation in L3-L4, 56 patients in L4-L5, 48 patients in L5-S1, 11 patients in
      L4-L5 and L5-S1. The central type of lumbar disc herniation occurred in 22
      patients and the lateral type of herniation occurred in other 95 patients. The
      Protrusion type of herniation occurred in 32 discs, ruptured type in 73 discs,
      and free type in 12 discs. Ninety-eight patients had lumbar and leg pain in one
      side, and 19 patients in double sides. MED was used to remove the nucleus and
      decompress the nerve root canal. RESULTS: All the patients were followed up and
      the duration ranged from 48 to 84 months,with an average of 5.5 years. According
      to lumbar and leg pain evaluation criteria from spinal group of Chinese
      Orthopaedic Association, there were 93 patients got an excellent result, 16 good
      and 8 poor. CONCLUSION: Appropriate control indications and skillful surgical
      techniques are the key points to decrease the complication and to improve the
      curative effect.

PMID- 19108379
TI  - [Efficacy of Lugua polypeptide injection on active rheumatoid arthritis].
AB  - OBJECTIVE: To investigate the therapeutic effect of Lugua polypeptide on active
      rheumatoid arthritis (RA). METHODS: Fifty patients with active RA were selected
      for the study and were randomly divided into study group and control group.
      Patients in study group were treated with Lugua polypeptide intravenously at a
      dose of 16 mg per day and those in control group were given Celecoxib 200 mg
      twice a day for successive 2 weeks. Two groups were given the same basic
      treatment. Tenderness and swelling of joints, morning stiffness, erythrocyte
      sedimentation rate, C-reactive protein,rheumatoid factor and so on were recorded
      before and after treatment. RESULTS: The above index on joints in study group was
      significantly improved compared with that in control group and the level before
      treament. No apparent side effects were observed. CONCLUSION: Lugua polypeptide
      is effective and safe on active RA. It is a promising agent in the treatment of
      RA.

PMID- 19108380
TI  - [Influence of canthaxanthin on D-galactose induced osseous changes of rat].
AB  - OBJECTIVE: To study the influence of canthaxanthin on D-galactose induced osseous
      changes of rat. METHODS: Forty-five six-week-old Wistar male rats were randomly
      divided into model group, canthaxanthin group and young control group. In
      addition, 15 sixteen-month-old Wistar male rats were used as old control group.
      Model group and canthaxanthin group were given injections of D-galactose for 5
      months (20 mg/kg/once per-day) to cause aging of rat. Then routine osseous
      parameters were tested and compared among the 4 groups. RESULTS: Compared with
      young control group, the BMD, parameters of structural mechanics and
      biomechanics, bone calcium, manganese, magnesium and the content of
      hydroxyproline in the model group decreased significantly (P < 0.01), however,
      the content of bone phosphorus, the activity of bone and serum ALP increased
      significantly (P < 0.01). Those changes of the model group were the same as the
      old control group,but the changes in the canthaxanthin group significantly
      differed with the model group (P < 0.01). CONCLUSION: The high does of D
      galactose intake can cause aging and osteoporosis at the same time in rat, but
      canthaxanthin can prevent and inhibit D-galactose induced osseous changes.

PMID- 19108381
TI  - [The initial mechanism's investigation of pilose antler polypeptides resisting
      replicative senescence of rat chondrocyte].
AB  - OBJECTIVE: To investigate the mechanism of pilose antler polypeptides (PAP)
      resisting replicative senescence of rat chondrocyte serially subcultivated in
      vitro by means of PAP interfering and controlled experiment. METHODS: The
      successive tert-generation (2nd passage, 3rd passage, 4th passage) chondrocytes
      and the 4th passage cells intervented by PAP were studied for senenscence
      mechanism. In this course, immunocytochemistry was applied for pl6, pRb, E2F,
      CyclinD, CDK4 and TRAP-ELISA (telomerase repeat amplification protocol assay
      enzyme linked immunosorbent assay) was applied for telomerase activation to
      observe targets' changing regarding to senescence and the function of PAP.
      RESULTS: Along with cell's replicative senescence, pl6, pRb and Cyclin D express
      significantly rised (P < 0.01), while E2F, CDK4 and telomerase express
      significantly lowerd (P < 0.01). Meanwhile, in PAP interfered group compared with
      which in 4th passage group, pl6, pRb and Cyclin D express significantly lowerd (P
      < 0.01l), while E2F, CDK4 and telomerase express significantly rised (P < 0.01).
      CONCLUSION: PAP has function that it reversingly affect the express of factors
      which controlling cell life cycle and cell growth to postpone chondrocyte
      senenscence.

PMID- 19108382
TI  - [Research of open situation x-ray of cervical vertebra in healthy people].
AB  - OBJECTIVE: To investigate the incidence rate of the different width in two sides
      of vertebra and C2 spinal process tilt, and analyze the different incidence rate
      between the unusual change of open situation x-ray and migraine. METHODS: Among
      the 350 investigators, testing the open situation x-ray of cervical vertebra and
      the questionnaire of migraine situation (163 male and 187 female with an average
      age of 39.6 years ranging from 26 to 54 years). They were divided into several
      groups according to the age, including 94 people from 26 to 34 years, 103 people
      from 35 to 44 years, 153 people from 45 to 54 years. The method of contrasting
      the incidence rate of open situation x-ray with the rate of migraine was used.
      RESULTS: Among the 350 investigated people, the incidence rate of the different
      width in two sides of vertebra and C2 spinal process tilt was 32.28%. The
      relationship between the different width in two sides of vertebra and the rate of
      migraine is not obvious (P > 0.05). However,the relationship between C2 spinal
      process tilt and the migraine was obvious (0.05 > P > 0.01). CONCLUSION: The
      difference between the different width in two sides of vertebra and the rate of
      migraine is not obvious in the investigated people, so it is not reliable to
      diagnose the illness as cervical vertebra disease. While the difference between
      the C2 spinal process tilt and the migraine is obvious, it is one of the reasons
      to diagnose the migraine.

PMID- 19108383
TI  - [Treatment of acetabulum fracture combined with ipsilateral lower extremity
      fracture].
AB  - OBJECTIVE: To discuss the treatment and mechanisim of acetabulum fracture
      combined with ipsilateral lower extremity fracture. METHODS: Fourteen cases(9
      males and 5 females) of acetabulum fracture were involved in the study with the
      mean age of 35 years (range, from 18 to 65 years). According to Letournel
      classification, 11 cases were the fracture of posterior wall and column, 3 cases
      were only the fracture of posterior column. All of them were treated with
      titanium plate internal fixation. Of three cases with ipsilateral femoral
      intertrochanteric fracture, one was treated with external fixiation device, other
      two were treated with DHS fixation; Three cases with ipsilateral femoral neck
      fracture were treated with compressive cannulated screw fixation; Among six cases
      with ipsilateral femoral shaft fracture,one was fixed with steel plate,the rest
      underwent intramedullary nailing fixation; Two cases with ipsilateral tibial
      plateau fracture were treated with anatomic plate internal fixation. RESULTS: All
      patients except the died old patient were followed up from 18 months to 5 years,
      with mean of 30 months. According to standard of American institute of
      orthopaedics, 9 cases obtained excellent results, 3 good and 2 poor and the
      excellent and good rate was 92.3%. CONCLUSION: Most cases of acetabulum fracture
      combined with ipsilateral lower extremity fracture are due to great violence,
      their mechanisms are complex, and easily lead to missed diagnosis, therefore the
      early correct diagnosis, and reasonable internal fixation should be considered.

PMID- 19108384
TI  - [Therapeutic effect of combined multifunctional external fixator for treatment of
      tibiofibular fracture].
AB  - OBJECTIVE: To study the therapeutic effect of combined multifunctional external
      fixator for treatment of tibiofibular fracture. METHODS: From Oct 1999 to Apr
      2006, 37 patients of tibiofibular fractures were treated with combined
      multifunctional external fixator. There were 28 males and 9 females with an
      average of 47.8 years (range,from 22 to 76 years). There were 7 cases with
      transverse fracture, 18 comminuted fracture, 8 spiral fracture and 4 oblique
      fracture;closed fracture was in 29 cases and open fracture was in 8. RESULTS: All
      the patients were followed up 6 to 13 months (mean,9 months)and achieved union of
      the fractures. CONCLUSION: Combined multifunctional external fixator for
      tibiofibular fracture has many advantages such as minimal invasion, convenient
      operation, reliable fixation and high union ratio of fracture. Moreover,the
      treatment has no influence on motion of knee and ankle joint, even patient can
      walk with external fixator without long-term bed rest.

PMID- 19108385
TI  - [Weber B fracture-dislocation of the ankle with compartment syndrome of the foot:
      a case report].

PMID- 19108386
TI  - [Spontaneous fracture of the fibular by osteochondroma in low tibiofibular
      syndesmosis: a case report].

PMID- 19108387
TI  - [Surgical treatment of open Pilon fractures].

PMID- 19108388
TI  - [Application value of traction in herniated lumbar intervertebral disc after
      percutaneous laser disc decompression].

PMID- 19108389
TI  - [Combined posterior and anterior approaches for the management of cervical
      spondylotic myelopathy by one-stage].

PMID- 19108390
TI  - [Treatment of lumbar intervertebral disc protrusion with tapping technique of
      negative pressure in 296 cases].

PMID- 19108391
TI  - [Manual reduction of children's Monteggia fractures].

PMID- 19108392
TI  - [Manipulation of lever location for treatment of lumbar disc herniation].

PMID- 19108393
TI  - [Studies on prescriptions for wound-healing and bone-setting].

PMID- 19108394
TI  - [Current state and development in surgical treatment for children with spinal
      tuberculosis].
AB  - This article reviews a large number of recent years' literatures about surgical
      treatment for children with spinal tuberculosis on the characteristics of
      children with spinal tuberculosis, and analyzes the development of surgical
      treatment for children with spinal tuberculosis. Then it summarizes the
      indications of surgical treatment for children with spinal tuberculosis, and
      analyzes the clinical effect of various surgical methods of spinal tuberculosis,
      assesses that anterior debridement combined with anterior and posterior interbody
      autografting can be a good growth rate and deformity correction. Pedicle fixation
      on the children with spinal tuberculosis is safe and feasible. The positive early
      surgery can control children kyphosis. Minimally invasive surgery is the
      development direction of treatment for children spinal tuberculosis.

PMID- 19108395
TI  - Wnt signaling. Pathway methods and mammalian models. Preface.

PMID- 19108396
TI  - Meeting the challenges of globalisation and miniaturisation in laboratory
      services.
AB  - In the recent years, two trends emerged in the clinical laboratory: the
      miniaturisation of equipments to provide point-of-care testing (POCT) and a
      concentration of laboratories through mergers and acquisitions. New technology
      has expanded both opportunities. POCT provides the benefit of a convenient test
      where it is needed, i.e. near the patient. For companies, it is easier and
      cheaper to develop such tests, since technical requirements are somewhat less
      stringent, being an interesting area for start-ups. Nanotechnology is one of the
      most fascinating technical advances, with some advocating a US$1 trillion market
      size for it by 2015. Laboratory tests and biomaterials will probably be greatly
      influenced by it, with new approaches for molecular diagnosis, with tests that
      can target both DNA and proteins in a process that eliminates PCR and allows
      multiplex analysis. On the other hand, there is a strong trend towards the
      globalisation of clinical laboratories and that occurs in four areas: a)
      Consumption of health services abroad; b) Movement of Health Personnel; c) Cross
      Border delivery of trade; and d) Commercial presence. Each of these areas
      presents new challenges and opportunities for clinical laboratories, what will
      certainly shape the way we work today and in the future.

PMID- 19108397
TI  - Lessons from the Nipah virus outbreak in Malaysia.
AB  - The Nipah virus outbreak in Malaysia (September 1998 to May 1999) resulted in 265
      cases of acute encephalitis with 105 deaths, and near collapse of the billion
      dollar pig-farming industry. Because it was initially attributed to Japanese
      encephalitis, early control measures were ineffective, and the outbreak spread to
      other parts of Malaysia and nearby Singapore. The isolation of the novel
      aetiological agent, the Nipah virus (NiV), from the cerebrospinal fluid of an
      outbreak victim was the turning point which led to outbreak control 2 months
      later. Together with the Hendra virus, NiV is now recognised as a new genus,
      Henipavirus (Hendra + Nipah), in the Paramyxoviridae family. Efforts of the local
      and international scientific community have since elucidated the epidemiology,
      clinico-pathophysiology and pathogenesis of this new disease. Humans contracted
      the infection from close contact with infected pigs, and formed the basis for pig
      culling that eventually stopped the outbreak. NiV targeted medium-sized and small
      blood vessels resulting in endothelial multinucleated syncytia and fibrinoid
      necrosis. Autopsies revealed disseminated cerebral microinfarctions resulting
      from vasculitis-induced thrombosis and direct neuronal involvement. The discovery
      of NiV in the urine and saliva of Malaysian Island flying foxes (Pteropus
      hypomelanus and Petropus vampyrus) implicated these as natural reservoir hosts of
      NiV. It is probable that initial transmission of NiV from bats to pigs occurred
      in late 1997/early 1998 through contamination of pig swill by bat excretions, as
      a result of migration of these forest fruitbats to cultivated orchards and pig
      farms, driven by fruiting failure of forest trees during the El Nino-related
      drought and anthropogenic fires in Indonesia in 1997-1998. This outbreak
      emphasizes the need for sharing information of any unusual illnesses in animals
      and humans, an open-minded approach and close collaboration and co-ordination
      between the medical profession, veterinarians and wildlife specialists in the
      investigation of such illnesses. Environmental mismanagement (such as
      deforestation and haze) has far-reaching effects, including encroachment of
      wildlife into human habitats and the introduction of zoonotic infections into
      domestic animals and humans.

PMID- 19108398
TI  - Genetic diversity of enterovirus 71 isolated from cases of hand, foot and mouth
      disease in the 1997, 2000 and 2005 outbreaks, Peninsular Malaysia.
AB  - All known field isolates of enterovirus 71 (EV71) can be divided into three
      distinct genogroups (A, B, C) and 10 subgenogroups (A, B1-5, C1-4) based on VP1
      gene sequences. We examined VP1 gene sequences of 10, 12 and 11 EV71 strains
      isolated in peninsular Malaysia during the outbreaks of hand, foot and mouth
      disease in 1997, 2000 and 2005 respectively. Four EV71 strains isolated in the
      hand, foot and mouth disease outbreak of 2006 in Sarawak (Malaysian Borneo) were
      included to describe their genetic relationship. Four subgenogroups (C1, C2, B3
      and B4) of EV71 co-circulated and caused the outbreak of hand, foot and mouth
      disease in peninsular Malaysia in 1997. Two subgenogroups (C1 and B4) were noted
      to cause the outbreak in 2000. In the 2005 outbreak, besides EV71 strains of
      subgenogroup C1, EV71 strains belonged to subgenogroup B5 were isolated but
      formed a cluster which was distinct from EV71 strains of the subgenogroup B5
      isolated in 2003. The four EV71 strains isolated from clinical specimens of
      patients with hand, foot and mouth disease in the Sarawak outbreak in early 2006
      also belonged to subgenogroup B5. Phylogenetic analysis of the VP1 gene sequences
      showed that the four Sarawak EV71 isolates belonged to the same cluster as the
      EV71 strains that were isolated in peninsular Malaysia as early as May 2005. The
      data suggested that the EV71 strains causing the outbreak in Sarawak could have
      originated from peninsular Malaysia.

PMID- 19108399
TI  - Comparison of PCR-based genotyping methods for hepatitis B virus.
AB  - Hepatitis B virus (HBV) is classified into eight genotypes (A to H). In this
      study, three genotyping methods were compared for their sensitivity and accuracy,
      namely PCR-RFLP on the S region, PCR-RFLP on the pre-S region and nested PCR with
      type specific primers. Sixty HBV samples from infected sera were genotyped. The
      nested PCR with type specific primers was found to be the most sensitive and
      produced substantial numbers of co-infections by genotypes B and C. The
      sensitivities for both PCR-RFLP methods were lower and did not reveal co
      infections. Generally, the three methods produced consistent genotyping results
      in samples infected by single genotypes but for co-infections by genotypes B and
      C, the two PCR-RFLP methods yielded only single genotypic results. For the cases
      of single genotypic infections, genotypes ascertained by sequencing were in
      concordance across all three methods. However, when co-infections occurred, PCR
      analysis on clones revealed only single genotypic infections.

PMID- 19108400
TI  - Serogroups and antibiotic susceptibility patterns of Neisseria meningitidis
      isolated from army recruits in a training camp.
AB  - Invasive Neisseria meningitidis infection is rare but carries a high mortality
      rate. The carriage rate in the normal population is around 10% and can be higher
      in confined populations. A study on the prevalence of carriage of N. meningitidis
      was conducted among 3195 army recruits after 2 months of intensive training in an
      army camp. N. meningitidis was isolated from 37.0% of these recruits. Two hundred
      and ten of N. meningitidis isolates were subjected to serogrouping and 100 to
      antibiotic sensitivity testing by the disc diffusion method and E-test for
      penicillin. Ten (4.8%) of 210 Neisseria meningitidis serogrouped belonged to
      serogroup W135, 3.33% serogroup A and 81.4% belonged to either serogroup X, Y or
      Z. With the agar disc diffusion method, all the N. meningitidis showed
      susceptiblity to chloramphenicol, rifampicin, cefotaxime and levofloxacin; 85% of
      the strains were resistant to cotrimoxazole and 12.5% resistant to penicillin.
      However, based on minimum inhibitory concentration, none of the Neisseria
      meningitidis tested was resistant to penicillin.

PMID- 19108401
TI  - Prostatic acid phosphatase in breast cyst fluid.
AB  - Prostatic Acid Phosphatase (PAP) is mostly found in the epithelial cells and
      secretions of the prostate gland. It has also been found to be present in several
      tissues and biological fluid. Gross cystic breast disease is the commonest benign
      breast condition and several studies have shown that women with palpable breast
      cysts may have a higher risk of developing breast cancer. There are two types of
      breast cyst and women with apocrine breast cyst may have a higher risk of
      developing breast cancer than women with breast cysts lined by flattened
      epithelium. The growth inhibitory effect of transforming growth factor beta (TGF
      beta) on epithelial cells suggests a potential protective role in breast cancer.
      TGF-beta is secreted as a high molecular weight complex in a biologically
      inactive or latent form and activation of TGF-beta is necessary for the exertion
      of its effects on target cells. Prostate specific antigen (PSA) has been found in
      breast cyst fluid (BCF) and it may have a protective effect on the development of
      several carcinomas by activating TGF-beta. As a similar molecule to PSA, PAP may
      also involve in this mechanism. We investigated the presence of PAP in two groups
      of BCF using an ELISA kit. PAP was found to be present in BCF but there was not a
      statistically significant difference between the two cyst groups. The presence of
      PAP in BCF may suggest its possible role in the development of breast cancer from
      cystic breast diseases. A possible role of PAP on TGF-beta activation needs
      further investigation.

PMID- 19108402
TI  - The use of immunohistochemistry in an oral pathology laboratory.
AB  - Immunohistochemistry has become part of normal routine diagnostic work in the
      Stomatology Unit, Institute for Medical Research, Kuala Lumpur. Of 9523 cases
      received from the year 2000 to 2005, 197 cases (2.1%) required
      immunohistochemical staining. These cases ranged from benign to malignant
      lesions. They include lymphomas (n=41), epithelial tumours (n=29), neural lesions
      (n=21), fibroblastic/myofibroblastic tumours (n=16), small round cell tumour
      (n=11), vascular tumours (n=4), smooth muscle tumours (n=4), myxomatous tumours
      (n=4) and skeletal muscle tumours (n=1). In most of the cases (69.5%),
      immunohistochemical staining was mandatory to reach a definite diagnosis, while
      60 cases (30.5%) required immunohistochemistry in confirming the diagnosis. In 32
      cases (16.2%), definitive diagnosis could not be made due to the small size of
      the specimens received or the results of immunohistochemistry were inconclusive.
      Standardization of techniques, competent medical laboratory technologists and
      sufficient budget allocation are important in producing a high quality
      immunohistochemistry service.

PMID- 19108403
TI  - Transient abnormal myelopoeisis in newborns with Down syndrome.
AB  - Transient abnormal myelopoeisis (TAM) is a haematological phenomenon commonly
      seen in newborns with Down syndrome. Although the majority show spontaneous
      resolution, this condition should not be dismissed too readily as there have been
      associated fatalities. Furthermore, even for those who do show spontaneous
      resolution, a significant percentage will develop acute megakaryoblastic
      leukaemia within the next few years of life. We report a series of four patients
      with TAM who presented with hepatosplenomegaly and leucocytosis detected on
      preliminary investigations.

PMID- 19108404
TI  - Bone marrow necrosis preceding infantile acute lymphoblastic leukaemia.
AB  - We report a case of bone marrow necrosis preceding infantile acute lymphoblastic
      leukaemia (ALL). Bone marrow necrosis is a rare antemortem event and has been
      known to be present in many conditions, notably in haematological malignancies
      like acute lymphoblastic leukaemia. This case was a 6-month-old Chinese boy who
      was referred to Hospital Universiti Kebangsaan Malaysia for further investigation
      of pancytopaenia, high-grade fever, bloody diarrhoea and petechial rashes for one
      week. His first bone marrow aspirate revealed bone marrow necrosis. His clinical
      condition improved after ten days. However, his full blood picture then revealed
      the presence of 5% blast cells. His subsequent marrow 2 weeks later revealed
      acute lymphoblastic leukaemia (FAB-L1) and immunophenotyping showed precursor B
      acute lymphoblastic leukaemia-null type. He was started on United Kingdom Acute
      Lymphoblastic leukaemia (UK ALL) Infantile Leukaemia protocol, however, he
      defaulted treatment after 3 days. Mode of presentation, mechanism of disease and
      laboratory investigations and outline of treatment will be discussed.

PMID- 19108405
TI  - The Pathology Laboratory Act 2007 explained.
AB  - The past century has seen tremendous changes in the scope and practice of
      pathology laboratories in tandem with the development of the medical services in
      Malaysia. Major progress was made in the areas of training and specialization of
      pathologists and laboratory technical staff. Today the pathology laboratory
      services have entered the International arena, and are propelled along the wave
      of globalization. Many new challenges have emerged as have new players in the
      field. Landmark developments over the past decade include the establishment of
      national quality assurance programmes, the mushrooming of private pathology
      laboratories, the establishment of a National Accreditation Standard for medical
      testing laboratories based on ISO 15189, and the passing of the Pathology
      Laboratory Act in Parliament in mid-2007. The Pathology Laboratory Act 2007 seeks
      to ensure that the pathology laboratory is accountable to the public, meets
      required standards of practice, participates in Quality Assurance programmes, is
      run by qualified staff, complies with safety requirements and is subject to
      continuous audit. The Act is applicable to all private laboratories (stand alone
      or hospital) and laboratories in statutory bodies (Universities, foundations). It
      is not applicable to public laboratories (established and operated by the
      government) and side-room laboratories established in clinics of registered
      medical or dental practitioners for their own patients (tests as in the First and
      Second Schedules respectively). Tests of the Third Schedule (home test blood
      glucose, urine glucose, urine pregnancy test) are also exempted. The Act has 13
      Parts and provides for control of the pathology laboratory through approval (to
      establish and maintain) and licensing (to operate or provide). The approval or
      license may only be issued to a sole proprietor, partnership or body corporate,
      and then only if the entity includes a registered medical practitioner. Details
      of personnel qualifications and laboratory practices are left to be specified by
      the Director-General of Health, providing for a formal recognition process and
      room for revision as pathology practices evolve. Encompassed in the
      responsibilities of the licensee is the requirement that samples are received and
      results issued through, and management vested in, a registered medical or dental
      practitioner. This effectively prohibits "walk-ins" to the laboratory and
      indiscriminate public screening. The requirement for a person-in-charge in
      accordance with class and speciality of laboratory ensures that the laboratory is
      under the charge of the pathology profession. Examined carefully, the
      requirements of the Act are similar to laboratory accreditation, but are backed
      by legislation. Many of these details will be spelt out in the Regulations, and
      these in turn are likely to fall back on National professional guidelines, as
      accreditation does. Although not at first obvious, enforcement of the Act is
      based on self-regulation by pathology laboratory professionals. Sincere
      professional input is thus required to embrace its philosophy, ensure rational
      and transparent enforcement of legislation, and develop National guidelines for
      good pathology practices upon which enforcement may be based.

PMID- 19108406
TI  - In-vitro differentiation study on isolated human mesenchymal stem cells.
AB  - Mesenchymal stem cells are pluripotent progenitors that could be found in human
      bone marrow. Mesenchymal stem cells are capable of renewing themselves without
      differentiation in long-term culture. These cells also have low immunogenicity
      and can suppress alloreactive T cell responses. In the current study, mesenchymal
      stem cells isolated and propagated previously from the bone marrow of a
      megaloblastic anaemia patient were tested for their capabilities to differentiate
      into adipocytes, chondrocytes and osteoblasts in vitro. The differentiated cells
      were determined by Oil Red O, Alcian Blue-PAS and Alizarin Red S staining, and
      reverse transcriptase-polymerase chain reaction to determine the expression of
      mRNA specific for adipogenesis, chondrogenesis and osteogenesis. The results
      showed that the fibroblast-like cells were capable of differentiating into
      adipocytes, chondrocytes and osteoblasts upon chemical induction. The adipocytes,
      chondrocytes and osteoblasts were stained positively to Oil Red O, Alcian Blue
      PAS and Alizarin Red S respectively. The differentiated cells were also found to
      express mRNA specific for adipogenesis ('peroxisome proliferation-activated
      receptor gamma2' and lipoprotein lipase), chondrogenesis (collagen type II) and
      osteogenesis (osteocalcin, osteopontin and alkaline phosphatase). In conclusion,
      this research has successfully isolated fibroblast-like cells from human bone
      marrow and these cells demonstrated morphological, cytochemical and
      immunochemical characteristics similar to mesenchymal stem cells. These cells
      maintain their proliferative properties and could be differentiated into the
      mesoderm lineage. The success of this study is vital because mesenchymal stem
      cells can be used in cellular therapy to regenerate or replace damaged tissues,
      or as a vehicle for therapeutic gene delivery in the future.

PMID- 19108407
TI  - A clinicopathological study of nine cases of gallbladder carcinoma in 1122
      cholecystectomies in Johor, Malaysia.
AB  - An audit of 1122 cholecystectomies for a 6-year period from 2000 to 2005 was done
      to review cases of primary carcinoma of gallbladder. There were nine cases of
      primary carcinoma of gallbladder. Six were females and 3 males. Their ages ranged
      from 27 to 81 years. Pre-operatively, only 2 (11.1%) were clinically suspected of
      carcinoma while 3 were diagnosed as cholecystitis, two as cholelithiasis and one
      case each of ovarian cyst and intestinal obstruction. Intra-operatively, an
      additional four cases were suspected as gallbladder carcinoma with the remaining
      three cases diagnosed as only having gallstones. Altogether only 5 (55.6%) cases
      were associated with gallstones. Six (66.67%) cases of gallbladder carcinoma had
      abnormal macroscopical lesions noted; either papillary lesions or polypoid
      masses. The remaining 3 cases had thickening of the wall, consistent with chronic
      cholecystitis. Seven cases were found histologically to be adenocarcinoma. Of
      these, two were papillary carcinoma and one signet ring cell type adenocarcinoma.
      One case of squamous cell carcinoma and one case of adenosquamous carcinoma were
      noted. This study highlights the importance of careful macroscopical and
      microscopical evaluation of a routine pathological examination of gallbladder
      removed for cholecystitis or cholelithiasis. It provides the incidence of
      gallbladder carcinoma in patients who underwent cholecystectomies in a government
      hospital in Johor, Malaysia.

PMID- 19108408
TI  - Histopathological evaluation of chronic gastritis with and without Helicobacter
      pylori colonization: a study from Iran.
AB  - Chronic gastritis is defined as the presence of chronic mucosal inflammatory
      changes leading eventually to mucosal atrophy and epithelial metaplasia. It is
      notable for distinct causal subgroups and for patterns of histological
      alterations that vary in different parts of the world. By far the most important
      aetiological association is chronic infection by the bacillus Helicobacter pylori
      (Hp). The organism is a worldwide pathogen that has the highest infection rates
      in developing countries including Iran. In this study, samples confirmed for the
      diagnosis of chronic gastritis from 100 Hp-positive and 36 Hp-negative patients,
      were reevaluated histopathologically to determine the severity of inflammation,
      the presence of active gastritis, lymphoid follicle(s), glandular atrophy and
      intestinal metaplasia. Seventy-five percent of the samples showed mild
      inflammation, whilst moderate and severe inflammation was seen respectively in
      24% and about 1% of the cases. Among the evaluated variables, only activity and
      intestinal metaplasia had statistically significant associations with Hp (p <
      0.05) in this survey.

PMID- 19108409
TI  - Isolation of purified autologous peripheral blood CD34+ cells with low T cell
      content using CliniMACS device--a local experience.
AB  - INTRODUCTION: Peripheral blood stem cells (PBSC) mobilised with growth factor
      with or without chemotherapeutic regimens, are used increasingly in both
      autologous and allogeneic transplantation. Previously, many PBSC harvests are
      used directly without ex vivo manipulation, and these PBSC have been shown to be
      contaminated with tumour cells, which may contribute to subsequent relapses post
      transplantation. Therefore, requirement for purging of malignant cells from the
      harvest has initiated the use of various methods to reduce tumour cell
      contamination of the graft by the positive selection of CD34+ progenitor cells or
      negative selection of tumour cells using other cell-specific antigens. We report
      here our local experience with the CliniMACS (magnetic-activated cell separation
      system) in eight adult patients with haematologic malignancies. OBJECTIVE: To
      evaluate the purity, recovery and viability of CD34+ cells selected from
      harvested peripheral blood stem cells using the CliniMACS device, as well as to
      evaluate the T and B cell contents of these products. METHOD: Eight adult
      patients with malignant haematological diseases (5 non-Hodgkin's lymphomas in 2nd
      complete remission (CR) and 3 acute myeloid leukaemias in 1st CR) were mobilised
      with granulocyte colony-stimulating factor (G-CSF) with or without
      chemotherapeutic regimens. A total of nine leukaphereses for peripheral blood
      stem cell harvest using the Cobe Spectra cell separator (Cobe BCT Lakewood, CO)
      were performed. The harvested PBSC were then positively selected for CD34+ cells
      using the CliniMACS device (Milteny Biotech, Germany). RESULTS: A total of nine
      leukapheresis products from eight adults with a median pre-selection total CD34+
      cell count of 282.2 x 10(6) (range 103.7 - 738.2 x 10(6)) were positively
      selected with CliniMACS. The median post-selection total CD34+ cell count was
      99.5 x 10(6) (range 7.7 - 443.9 x 10(6)) with the median recovery was 66.0%
      (range 2 - 94%) and median purity of products of 79% (range 18 - 86%). The median
      total T cell count was reduced dramatically from 3.1 x 10(9) pre-selection to 7.9
      x 10(6) post-selection. The selection did not affect the viability of selected
      cells that was tested with trypan blue exclusion method with a median pre and
      post selection viabilities of 98% (range 95 - 98%). CONCLUSION: We conclude that
      positive selection of CD34+ cells using magnetic separation technology by
      CliniMACS device results in low T-cell content stem cell with acceptable purity
      and recovery for autologous peripheral blood stem cell transplantation.

PMID- 19108410
TI  - Detection of the human papillomavirus in cervical carcinoma: a comparison between
      non-isotopic in-situ hybridisation and polymerase chain reaction as methods for
      detection in formalin-fixed, paraffin-embedded tissues.
AB  - Cervical carcinoma, the second most common malignancy in Malaysian females, is
      aetiologically linked to the human papillomavirus (HPV). A study was conducted at
      the Department of Pathology, University of Malaya Medical Centre to compare the
      identification of HPV 6, 11, 16 and 18 in 40 archived formalin-fixed, paraffin
      embedded cervical carcinoma by non-isotopic in-situ hybridisation (NISH) and
      polymerase chain reaction (PCR). HPV L1 ORF consensus PCR was also carried in
      cases which were negative on HPV type-specific PCR. NISH detected HPV 16 in 13
      (32.5%) cases with one case demonstrating a concomitant HPV 18. beta-globin DNA
      PCR was carried out on the same paraffin block as for NISH in 27 cases and on a
      different paraffin block in 13, with amplification in 9 of the former and 3 of
      the latter. Thus only 12 cases were subjected to further HPV PCR. HPV was
      detected in 10 (83.3%) with HPV 16 in 9 cases and HPV L1 ORF in one. When using
      the same paraffin block for both methods of HPV detection, NISH detected HPV in 6
      and PCR in 7. NISH failed to detect HPV in a case detected by PCR. 2 cases were
      negative for HPV using both methods. Hence, HPV detection results by NISH and PCR
      were concordant in 88.9%. Interestingly, NISH detected HPV in 2 cases with non
      amplifiable beta-globin DNA. Using an alternative paraffin block for HPV PCR from
      NISH, HPV DNA was detected in 3 cases, two of which also showed type-specific
      positivity on NISH. The third case did not reveal type-specific positivity with
      NISH or PCR but demonstrated HPV DNA on L1 ORF consensus PCR. It thus appears
      that PCR and NISH can be successfully used to detect HPV in formalin-fixed,
      paraffin-embedded tissue and in the presence of intact DNA NISH may be as
      sensitive as PCR.

PMID- 19108411
TI  - Prostate-specific antigen in breast disease.
AB  - The aim of this study is to assess tissue and serum prostate-specific antigen
      (PSA) in breast lesions; to compare tissue PSA with serum PSA; to compare tissue
      PSA in benign and malignant lesions and to compare PSA with known prognostic
      factors in breast carcinoma. Tissue PSA immunoreactivity in twenty women with
      breast carcinoma was compared with PSA in twenty-three women with benign breast
      lesions. Tissue PSA was also compared with known prognostic indicators such as
      tumour size, axillary nodal status, histological type, histological grade,
      oestrogen receptor status, progesterone receptor status and c-erbB-2 oncoprotein
      over-expression. Serum free PSAlevels from these women were measured pre- and
      post-operatively and an attempt was made to correlate serum PSA with tissue PSA
      expression. 40% and 43% of malignant and benign breast lesions respectively
      showed tissue PSA immunoreactivity. No significant difference was observed in the
      tissue PSA expression between these two groups as also between tissue PSA and
      known prognostic indicators. As serum PSA levels were below the detection limit
      (< 0.004 ng/ml) in all except two benign cases, no statistical evaluation was
      done for the latter. Tissue PSA expression did not correlate with other
      prognostic markers and detectable serum PSA levels were present in too few cases
      for statistical analysis. Although no definitive conclusion is possible in this
      preliminary study regarding the role of PSA in breast disease, it stimulates
      interest in further research in this direction.

PMID- 19108412
TI  - An outbreak of Paederus dermatitis in a primary school, Terengganu, Malaysia.
AB  - Outbreaks of Paederus dermatitis have been reported in several Asia-Pacific
      countries when rove beetles (genus Paederus) are accidentally brushed or crushed
      on the skin, releasing haemolymph pederin. An investigation was conducted in a
      school to ascertain the causative agent, establish the case definition,
      epidemiological characterisation of cases, entomological and environmental survey
      and data analysis. This outbreak occurred among 36 schoolchildren attending a
      night tuition class conducted by their teacher. Dermatitis developed within 24
      hours in 33/37 (89.2%) cases with itchiness as the first presenting symptom in
      87.9% of cases. Periorbital oedema and erythematous-vesicular plaques on the
      upper extremities were seen in 57.6% of cases, on the back (36.4%) and on the
      nape (24.2%). Signs and symptoms were present 12 hours after exposure in 66.7% of
      cases with burning sensation within four hours in 9.1%. Seven cases received out
      patient treatment. Thirty cases (90.9%) recalled exposure to Paederus fuscipes
      with 28 (84.8%) cases admitting crushing or brushing the insects. (Relative risk
      = 2.2; 95% CI: 1.2; 4.2). The school with fluorescent lighting, was located next
      to paddy fields. P. fuscipes was easily found in the paddy fields and along the
      school corridors. This strongly supports it as the likely causative agent for the
      dermatitis. Boarding the ventilation panes and use of insect spray were
      successfully implemented to control the outbreak. Increased awareness of this
      condition is important to prevent misdiagnosis.

PMID- 19108413
TI  - Fine needle aspiration cytology of neuroendocrine carcinoma of the breast--a case
      report and review of literature.
AB  - Neuroendocrine carcinomas of the breast are uncommon tumors known to occur in the
      elderly. While focal neuroendocrine differentiation may be noted in many ductal
      and lobular carcinomas, the term neuroendocrine carcinoma is to be applied when
      more than 50% of the tumor shows such differentiation. This case report details
      the cytological features of a neuroendocrine carcinoma that was encountered in
      our hospital. The fine needle aspiration (FNA) smears showed discohesive
      polygonal cells with abundant cytoplasm, many of which contained eosinophilic
      granules located at one pole. Histology of the mastectomy and axillary lymph
      nodes specimen from this patient showed features of neuroendocrine carcinoma-
      solid type, with metastasis, confirmed with immunohistochemistry. The patient is
      disease free seven months after surgery. This case highlights the need to closely
      observe cytological details to identify this rare tumor that may otherwise appear
      to be invasive duct carcinoma--not otherwise specified on FNA. The implications
      of diagnosing neuroendocrine differentiation for prognosis and management are
      also discussed.

PMID- 19108414
TI  - Multifocal nodal and extranodal Rosai-Dorfman disease initially diagnosed as
      histiocytic lymphoma.
AB  - Rosai-Dorfman disease (RDD), also known as sinus histiocytosis with massive
      lymphadenopathy (SHML), is a systemic disease involving nodal and extranodal
      tissues. We report a 48-year-old female with recurrent nasal obstruction due to
      polypoidal masses involving the nasal sinuses, turbinates and septum bilaterally,
      and lumps in the right infra-orbital region and region of the right lacrimal sac.
      A 4 cm right upper neck mass was also noted, which was initially diagnosed as
      histiocytic lymphoma. Histopathology of the nasal and infraorbital lesions
      revealed fibro-inflammatory masses containing histiocytic cells with large
      vesicular nuclei and abundant foamy cytoplasm exhibiting emperipolesis and
      lymphophagocytosis, admixed with scattered plasma cells and lymphocytes. These
      histiocytes revealed immunohistochemical positivity for S-100 protein and CD68,
      but were negative for CDla. The findings supported a diagnosis of RDD. This
      report serves to remind pathologists and clinicians of the extranodal
      manifestations of RDD and its potential confusion with lymphomas.

PMID- 19108415
TI  - [Study on indication, contraindication and complication of percutaneous
      vertebroplasty and kyphoplasty].

PMID- 19108416
TI  - [Clinical study on the vertebral plasty for the treatment of osteoporotic
      vertebral compressed fractures in elderly].
AB  - OBJECTIVE: To study therapeutic effects of Sky-bone expander for the treatment of
      osteoporotic vertebral compressed fractures. METHODS: Fifteen patients (18
      vertebrae) suffering from vertebral compression fractures were treated with Sky
      bone expander system which expanded and reconstructed the vertebral body with
      PMMA cement. The clinical effect was evaluated by observing the changing of
      visual analogue scale (VAS). The preoperative and postoperative mean VAS scores
      were compared by paired-sample t test. All the patients were followed up by
      telephone or clinic consulting after being discharged from our hospital. RESULTS:
      The procedure was performed successfully in 15 patients. The operation time
      ranged from 45 to 110 minutes (65 minutes per vertebra on average). The patients
      were followed up and the duration ranged from 6 to 12 months (8 months on
      average). The mean VAS score of the patients were improved significantly at the
      third postoperative day compared with those before the operation (2.5 +/- 1.3, vs
      7.7 +/- 1.1, all P < 0.05). The mean VAS score at the end of the follow-up was
      2.2 +/- 1.2. CONCLUSION: Sky bone expander system provides significant pain
      relief effect in the cases of osteoporotic vertebral compression fractures,
      shortens the duration of lying in bed, and its procedure is convenient with few
      complications.

PMID- 19108417
TI  - [All pedicle screws technique applied to the treatment of idiopathic scoliosis].
AB  - OBJECTIVE: To Analyze the therapeutic efficacy of all pedicle screws technique
      applied to the treatment of idiopathic scoliosis and evaluate its safety.
      METHODS: From June 2002 to October 2005, 56 patients with idiopathic scoliosis
      were treated with all pedicle screws technique, including 11 males and 45
      females, ranging in age from 8 to 22 years. According to Lenke classification, 29
      patients were Type 1, 6 patients were Type 2, 8 patients were Type 3, 2 patients
      were Type 4, 8 patients were Type 5, and 3 patients were Type 6. Cobb angles
      ranged from 45 degrees to 85 degrees (mean 62.45 degrees). RESULTS: The mean
      operation time was 3 hours and 20 minutes, and the average amount of bleeding was
      600 ml. There were 425 pedicle screws inserted including 244 in thoracic, and 181
      in lumbar, the positions of which were evaluated by CT. Nine screws were inserted
      with perforating through the medial wall of the pedicles. All the patients were
      followed up for 5 to 40 months (mean 22.5 months). The mean Cobb angle was
      corrected from 62 degrees preoperatively to 18 degrees postoperatively,and the
      average correction rate was 72.5%. No spinal nerves injury was found after
      operation, and superficial infection occurred in 2 patients but recovered after
      dressing change. All the patients got satisfactory spinal fusion and remained
      partly spinal mobility with fewer complications. CONCLUSION: The application of
      all pedicles screws technique with familar with pedicular anatomy of scoliosis by
      imaging examination could gain a satisfactory effect of correction with less
      complications.

PMID- 19108418
TI  - [Introduce a new method of intradermic continuous suture].

PMID- 19108419
TI  - [Study on reliablility of flexion-extension ratio in surface EMG for the
      diagnosis of nonspecific chronic low back pain].
AB  - OBJECTIVE: To evaluate the reliability of flexion-extension ratio (FER) of lumbar
      erector muscle in surface EMG for the diagnosis of nonspecific chronic low back
      pain. METHODS: According to diagnostic study strategies, 73 patients with chronic
      low back pain and 86 controls were recruited in this study, FER of lumbar erector
      muscle were recorded in surface EMG for all the subjects. The critical value of
      FER for the diagnosis of nonspecific chronic low back pain was selected according
      to the receiver operator characteristic curve by SPSS. Sensitivity, specificity
      and accuracy were calculated and analyzed as well. RESULTS: The FER in patients
      group was significantly higher than that in the control group. The critical value
      of FER was 0.68 with sensitivity, specificity and accuracy was 78.1%, 95.3% and
      87.4% respectively. CONCLUSION: FER of lumbar erector muscle might be practically
      applied as an objective indicator on the diagnosis of nonspecific chronic low
      back pain in surface EMG.

PMID- 19108420
TI  - [Imageology change of degenerative cartilage endplate to different degree and its
      clinical significance].
AB  - OBJECTIVE: To study the imageology changes of degenerative cartilage endplate to
      different degree, and to explore its clinical significances. METHODS: The
      imageology data (MRI or CT) of 58 patients with degenerative disc disease of L4,
      5 (including 34 patients with lumbar disc herniation). The patients were divided
      into three groups depending on the mean signal intensity rate of degenerative
      disc and cerebrospinal fluid: light degenerative group of 17 cases, intermediate
      degenerative group of 17 cases, and severe degenerative group of 24 cases. The
      signals of intervertebral disks on T2WI of sagittal magnetic resonance imaging
      were inputted into the computer and the concave angles of endplate were measured.
      Anteroposterior diameter and transverse diameter of the endplate were measured
      from the CT scan of L4, 5, and then the relative curvature of endplate was got.
      The change patterns of the concave angle and the relative curvature of vertebral
      endplates were analyzed when the lumbar disc was differently degenerative.
      RESULTS: (1) The concave angle of endplate (L4 inferior endplate, L5 superior
      endplate) gradually increased among the light degenerative group, intermediate
      degenerative group and severe degenerative group (P < 0.01). (2) The relative
      curature of endplate (L4 inferior endplate, L5 superior endplate) gradually
      increased. There was significant difference between the light degenerative group
      and intermediate degenerative group (P < 0.0l), and there was significant
      difference between the light degenerative group and severe degenerative group (P
      < 0.0l). There were no significant difference between intermediate degenerative
      group and severe degenerative group (P < 0.05). (3) The concave angle of endplate
      had positive correlation with relative circularity (r = 0.786, 0.490).
      CONCLUSION: The concave angle and relative curvature of endplate generate
      corresponding changes when the lumbar disc are differently degenerative. The
      changes of concave angle and relative curvature of endplate are important factors
      of lumbar disc hernia and lower back pain, which may evaluate the probability of
      intervertebral disk hernia.

PMID- 19108421
TI  - [Case-clinical studies on the applicator of external fixator in the open tibia
      and fibula fractured patients with multiple trauma].
AB  - OBJECTIVE: To explore the effects of early external fixation for open tibia and
      fibula fractures on the treatment and prognosis of severe multiple injuries.
      METHODS: Seventy-three patients were reviewed in the study. According to the
      surgical methods for tibia and fibula fractures, the patients with severe
      multiple injuries were divided into 2 groups: 42 patients in the treatment group,
      including 31 males and 11 females, with an average age of 40.2 years; 31 patients
      in the control group, ineluding 22 males and 9 females, with an average age of
      42.6 years. The patients in treatment group were treated urgently with
      debridement, diaplasis and fixation with external fixator, and patients in
      control group were treated urgently with debridement, calcaneal traction or
      gypsum external fixation. The incidence rate and mortality of ARDS and MODS,
      wound infection rate, wound healing time, and fracture healing time between the 2
      groups was compared. RESULTS: The incidence rate and mortality of complications
      (ARDS) had significant differences between the 2 groups, those in the treatment
      group were lower than those in the control group (P < 0.05). There were
      significant decreases in the infection rate and wound healing time in the
      treatment group. CONCLUSION: External fixation for severe multiple injuries with
      open tibia and fibula fracture has been proved to be good, which can
      significantly reduce the mortality and incidence rate of complications and wound
      infection rate, promote wound healing.

PMID- 19108422
TI  - [Case-clinical studies on three different intervertebral fusion with bone graft
      and internal fixation in the treatment of cervical spondylotic myelopathy].
AB  - OBJECTIVE: To evaluate the therapeutic effects of three different intervertebral
      fusion with bone graft and internal fixation in the treatment of cervical
      spondylotic myelopathy. METHODS: In the retrospective study, 83 patients (38
      males and 45 females, with an average age of 69 years) with cervical spondylotic
      myelopathy were divided into three groups. The patients in three groups were
      treated by autogenous iliac bone grafting (Robingson grafting) with anterior
      cervical plate-screw fixation, Pyramesh with anterior cervical plate-screw
      fixation and BAK fixation respectively. JOA scores and the bony fusion time were
      recorded and the results were evaluated by numeric computer system. RESULTS: The
      JOA scores of all the patients were higher than those before surgery (t = 1.55, P
      < 0.05). There were no statistical difference of JOA scores in the three groups
      (F = 2.51, P > 0.05). CONCLUSION: It is concluded that internal fixation of the
      three types is promising to the treatment of cervical spondlotic myelopathy.
      Robingson grafting with anterior cervical plate-screw fixation provides good
      stability and bony fusion. BAK is better technically required but there was
      height loss in clinic. Pyramesh with anterior cervical plate-screw fixation
      combines the merits of both two techniques above but the cost is higher.

PMID- 19108423
TI  - [Controlled randomized trial on therapeutic effects of acupotomy-injection
      combined with Feng's spinal manipulation (FSM) for cervical spondylotic
      radiculopathy].
AB  - OBJECTIVE: To evaluate the therapeutic effects of acupotomy-injection with FENG
      Tian-you spinal manipulation (FSM) for treating cervical spondylotic
      radiculopathy (CSR). METHODS: Seventy-two patients with CSR were randomly divided
      into two groups (n = 36 respectively): treatment and control group. The patients
      in treatment group were treated with acupotomy-injection combined with FSM, and
      patients in control group were treated with traction. All the patients were
      followed up for 3 months after treatment and the therapeutic effects were
      evaluated. RESULTS: Totally there were 72 patients and 69 completed the treatment
      and the other 3 patients withdraw from treatment. In treatment group, 24 patients
      were cured, 6 patients had remarkable effects, 4 effective and 2 ineffective; as
      well in control group, above data were 15, 3, 10 and 8 respectively. The
      comprehensive effects and the cured patients in the treatment group were
      obviously better than those of control group (P < 0.05). The comparison of scales
      for assessment of symptoms and short-form McGill Pain Questionaire before and
      after treatment in two groups had significant differences (P < 0.001).
      CONCLUSION: The method of acupotomy-injection combined with FSM for treating CSR
      is better than conventional traction method.

PMID- 19108424
TI  - [Effect of various external fixation for the treatment of Colles fracture].
AB  - OBJECTIVE: To observe restoration of the wrist function and complications of
      Colles fracture treated with different kinds of external fixation. METHODS: Two
      hundreds and seventy-five patients with Colles fracture during March 1998 to Oct
      2006 which were fixed with three kinds of external fixation were analyzed
      retrospectively. Group A: there were 95 patients, 61 male, 34 female, with an
      average age of (26.2 +/- 0.4) years, fixed by the small moulding plywood on the
      wrist in mild dorso-extend or neutral position; Group B:90 patients, 61 male, 29
      female, with an average age of (24.0 +/- 1.5) years, fixed by the small moulding
      plywood on the wrist in mild palmar flexion; Group C: 90 patients, 65 male, 25
      female, with an average age of (25.0 +/- 2.1) years, fixed by plaster on the
      wrist in mild dorso-extend or neutral position. According to the Frykaman
      typing,number of type I to VIII in group A was 25, 31, 20, 11, 3, 2 ,2, 1 in
      turn,type I to VIII in group B was 22, 30, 17, 9, 4, 4, 2, 2 in turn; type I to
      VIII in group C was 24, 30, 18, 9, 4, 3, 1, 1 in turn. Comparing the age, sex and
      the type of fracture, there were no statistical significant differences among
      three groups. After 6 to 18 months following-up survey, the restoration of the
      wrist and complication incidence were statistically analyzed. RESULTS: To compare
      the restoration of the wrist joint and complication incidence after various
      fixation, there were significant differences between group A and B and C (P <
      0.05) in statistics. CONCLUSION: The treatment of the Colles fracture by the
      small moulding plywood fixation on the wrist in mild dorso-extend or neutral
      position is benefit to restore the wrist joint function and has fewer
      complications..

PMID- 19108425
TI  - [Effects of cryopreserved neural stem cells transplantation on rat axonal
      regeneration after spinal cord injury].
AB  - OBJECTIVE: To observe the effects of cryopreserved (-70 degrees C) neural stem
      cells (NSCs) transplantation on the axon regeneration after the spinal cord
      injury (SCI) of rats. METHODS: Neural stem cells were cultured from the
      hippocampus of the rat's embryo and identified by immunocytochemistry of nestin,
      then NSCs in logarithmic phage were cryopreserved (-70 degrees C) for 2 weeks.
      Seven days after the operation of SCI, the NSCs in were transplanted into the
      injured site immediately. Thirty six adult Wistar rats were randomly divided into
      three groups: spinal cord injury treated with transplantation of NSCs to the
      injured site (Group A), spinal cord injury received DMEM solution (Group B),
      control group (Group C). Then NSCs labeled with Brdu were detected by
      immunohistochemisty, and the reconstruction of spinal cord were detected by
      horseradish peroxidase (HRP) staining. RESULTS: NSCs can be detected in the
      spinal cord after transplantation. The number of HRP positive cells of Group A
      was higher than that of Group B. CONCLUSION: The transplantation of cryopreserved
      NSCs can survived in the injured site and promote the reconstruction. It may be a
      progress in the repairing of the SCI by cells transplantation.

PMID- 19108426
TI  - [Experimental study on the effects of inactivated and un-inactivated pharmaco
      serum of diabetic rats fed with Chinese herbs Qianggubao decoction on the
      proliferation of osteoblast cultured in vitro].
AB  - OBJECTIVE: To study the effect of inactivated and un-inactivated pharmaco-serum
      of diabetic rats fed with Chinese herbs Qianggubao decoction on the proliferation
      of osteoblast cells (OB)cultured in vitro. METHODS: OB was isolated from the
      skull of newly born SD rats aged 1 to 2 days by means of Trypsin-collagenase
      digestion and identified by image analysis under inverted microscope, V-G
      collagen staining, ALP staining, calcification nod staining etc. After the OB was
      identified, in activated and un-inactivated pharmaco-serum of diabetic rats fed
      with Qianggubao decoction of ferent phase (rats were fed with medicine 3 days or
      5 days after last fed with medicine 1 hour or 3 hours) and concentration (5%,
      10%, 20%) were added to the OB and incubated. After determined times, the effects
      of the proliferation of osteoblasts were detected by MTT analysis. RESULTS: There
      was significant difference between un-inactivated pharmaco-serum and inactivated
      pharmaco-serum on the proliferation of osteoblasts, and un-inactivated serum had
      stronger effects to improve the proliferation of osteoblasts (P < 0.01 or P <
      0.05). CONCLUSION: Un-inactivated and inactivation pharmaco-serum of diabetic
      rats fed with Chinese herbs Qianggubao decoction can influence the proliferation
      of, and the un-inactivated pharmaco-serum has stronger effects.

PMID- 19108427
TI  - [Experiment research on the influence of Yanghe decoction on the expression of
      HIF-1alpha mRNA in osteoarthritis].
AB  - OBJECTIVE: To explore the influence of Yanghe decoction on the expression of HIF
      1alpha mRNA in osteoarthritis (OA), so as to study mechanisms of Yanghe decoction
      in the improvement of cartilagedegeneration. METHODS: Thirty New Zealand white
      rabbits were randomly divided into 3 groups: control group (10 rabbits), OA model
      group (10 rabbits) and Yanghe decoction treatment group (10 rabbits). The OA
      models were established by using Hulth method. The sections were stained with
      Safranin O for histological examination. Each sample was evaluated the cartilages
      histological characteristics according to the method of Mankin. Fluorescent
      quantitative PCR was used to detect the expression of HIF-1alpha mRNA in each
      group. RESULTS: There were significant differences in the Mankin score between
      the control group and the OA model group (P = 0.005), either between the OA model
      group and the Yanghe decoction treatment group (P = 0.003). Fluorescent
      quantitative PCR indicated that HIF-1alpha mRNA significantly increased in the OA
      model group compared to that of the control group (P = 0.035), but that
      expression was much lower in Yanghe decoction treatment group compared to that of
      the OA model group (P = 0.039). CONCLUSION: The expression of HIF-1alpha mRNA
      plays an important role in OA. Yanghe decoction is effective to protect the
      articular cartilage, which is achieved through regulating the expression of HIF
      1alpha mRNA.

PMID- 19108428
TI  - [Effect of exogenous interferon gamma on the healing of injured skeletal muscle
      following injury].
AB  - OBJECTIVE: To observe the influence of combined injection with human interferon
      (hlFNgamma) and human insulin-link growth factor-1 (hIGF-1) on regeneration and
      fibrosis of skeletal muscle after acute contusion. METHODS: A standard contusion
      model was reproduced at the right gastrocnemius in 64 male mice of 7 to 12 weeks.
      All the mice were randomly divided into 4 groups, such as group A (injection with
      hIFNgamma), group B (injection with hIGF-1), group C (injection with hIGF-1 and
      hIFNgamma), and group D (injection with physiological saline as control). All
      injections were introduced on day 10 after injury at local injured gastrocnemius.
      Before intervention (7 d following injury), and 4 d, 18 d, 32 d after
      intervention, the local injured gastrocnemius were harvested from 4 mice of each
      group. Then the expression of MHC- II b and vimentin was detected by real time
      PCR and immunohistochemistry techniques. RESULTS: (1) At the each time following
      intervention, the expression of MHC-II b mRNA and protein in local injured muscle
      of group B and C were significantly higher than those of group A and D. (2) After
      intervention,the expression of vimentin mRNA and protein in local injured muscle
      of group A, group B, and group C were more inhibited than those of group D. The
      inhibition of vimentin expression in group A and C was significant. CONCLUSION:
      It is indicated that injection of hIGF-1 into the injured skeletal muscle
      following acute contusion could enhance muscle regeneration,and inhibit fibrosis
      to some extent. (2) It is identified that hIFNgamma injected into injured muscle
      has the effect of anti-fibrosis, which is more significant than that of hIGF-1.
      (3) Combined injection with hIGF-1 and hIFNgamma could improve muscle
      regeneration and inhibit fibrosis simultaneously, and promote the healing of
      injured muscle.

PMID- 19108429
TI  - [Study on clinical characteristics and rehabilitative treatment for degeneration
      of cervical articular process].
AB  - OBJECTIVE: To investigate the pathogenesis and rehabilitative treatment for
      degeneration of cervical articular process. METHODS: Among 200 case of cervical
      disease with oblique radiography, 90 (45%) have different levels of facet
      degeneration, aged from 31 to 76 years, mostly in the elderly (accounting for
      80%). There are no significant differences between men and women. RESULTS: There
      are three reasons for cervical facet degeneration. (1) Physiological degeneration
      of the articular process; (2) Acute and chronic injuries, especially whiplash
      injury; (3) Iatrogenic injury. Among these causes, iatrogenic injury is very
      common and has been neglected for a long time. When the intervertebral joint is
      instable, chronic fatigue or acute injury will certainly produce symptoms,
      including symptoms of nerve root type, or vertebral artery type, or both types of
      cervical disease. CONCLUSION: Oblique X-ray films show that superior articular
      process protrudes into the intervertebral foramen, which causes intervertebral
      foramen narrow, and the narrow degree is in proportion to rising and extending
      range of head and neck. Scientific and dialectical therapy is the key to treat
      this disease, and manipulative reduction to enlarging intervertebral foramen with
      the neck at flexing position is a targeted treatment, which can treat symptoms
      and causes of the disease at the same time. If the case is special, cervical
      dynamic extension and flexion X-ray film should be taken.

PMID- 19108430
TI  - [Diagnosis and treatment of intervertebral disc disease based on the theory of
      "Gucuofeng and Jinchucao"].
AB  - It has previously been reported that the incidence rate of intervertebral disc
      disease including cervical and lumbar vertebra is at the 8th position among the
      chronic and difficult treated diseases in China. There are great challenges on
      the improving diagnosis and treatment as well as reducing recrudescence of this
      degenerative disease. It was well known that the degeneration and bulge or
      herniatation of intervertebral discs are the main reasons for it, and the
      treatment for it always focuses on the disc recovery. However, the discrepancy of
      the effect and expectation indicated that there were other reasons for it. Based
      on the clinical knowledge of intervertebral discs disease and combined with the
      cognition of Traditional Chinese Medicine,we proposed that the pathogenesis of
      intervertebral disc disease was Gucuofeng and Jinchucao, which meant that the
      improper location of diapophysis and the declined of muscle strength may cause
      the unstable of spine, unstable spine thus aggravated the semiluxation of
      diapophysis.

PMID- 19108431
TI  - [Clinical research on osteoprosis by traditional Chinese medicine (TCM)].

PMID- 19108432
TI  - [Recapping laminoplasty for the treatment of severe burst fractures of
      thoracolumbar vertebra complicated with spinal stenosis].
AB  - OBJECTIVE: To investigate operation skills, therapeutic effects and indications
      of racapping laminoplasty for the treatment of severe burst fractures of
      thoracolumbar vertebra complicated with spinal stenosis. METHODS: In the study,
      41 patients with severe burst fractures of thoracolumbar vertebra complicated
      with spinal stenosis were treated with recapping laminoplasty. After the
      treatment, the size of vertebral canal, spinal stability, altitude recovery of
      vertebral body and rehabilitation of nerve function were observed. RESULTS: All
      the patients were followed up and the duration ranged from 1 to 3 years. The
      anterior height of compressed vertebral bodies restored from preoperative 58% to
      postoperative 97%, posterior height was from preoperative 76% to postoperative
      98.7%. The Cobb angle was corrected from preoperative 24.6 degrees to
      postoperative 1.8 degrees, and the size of vertebral canal restored from
      preoperative 43% to postoperative 93%. According to Frankel classification, 1
      patient who were at A grade had no changes and others improved by 1 to 3 degrees.
      CONCLUSION: This is an ideal operation method for treating burst fractures of
      thoracolumbar vertebra with spinal stenosis, which is simple, safe and enlarging
      vertebral canal, at the same time completely decompressing the dura mater and
      nerve roots. This method eliminated secondary spinal stenosis, reconstructed
      posterior column and increased spinal stability.

PMID- 19108433
TI  - [Arthroscope combined with minimally invasive internal fixation for the treatment
      of tibial plateau fractures].
AB  - OBJECTIVE: To investigate the clinical results of arthroscope combined with
      minimally invasive internal fixation for the treatment of tibial plateau
      fractures. METHODS: Forty-two patients with tibial plateau fractures were treated
      with arthroscopically assisted limited invasive internal fixation. There were 27
      males and 15 females, with an average age of 38 years. Tibial plateau fractures
      were classified according to Schatzker staging system. There were 5 patients with
      type-I, 15 patients with type-II, 12 patients with type-III, 7 patients with type
      IV, 2 patients with type-V and 1 patient with type-VI. Forty patients were
      followed up, with an average of 18 months. Evaluations were performed according
      to Rasmussen functional score system. RESULTS: Over half (55%) of the patients
      had concomitant intra-articular lesions. The mean Rasmussen functional score was
      27 +/- 1. Nineteen patients got an excellent result, 16 good,and 5 fair. One
      patient suffered from joint stiffness (ROM: 0 to 90 degrees) and another patient
      developed degenerative arthritis during the follow-up period. CONCLUSION: The
      treatment has advantages of avoiding open the articular capsule, dealing with
      intra-articular lesions at the same time, decreasing the postoperative
      complications and profiting the recovery of knee joint.

PMID- 19108434
TI  - [Reduction by revolving and bending elbow and fixation with paper splints for the
      treatment of supracondylar fracture of humerus].
AB  - OBJECTIVE: To evaluate curative effect of the treatment on the extension type
      supracondylar fracture of humerus by revolving, and bending elbow and fixing with
      paper splint. METHODS: Thirty-five children with supracondylar fracture of
      extension type included 26 boys and 9 girls with an average age of 5.8 years,
      ranging from 2.5 to 10 years. The tine from injury was 0.5 to 18 hours. The
      elbows were flexed in 90 degrees, forearm was rotated, and fixed with paper
      splint. RESULTS: According to the elbow joint functional evaluation of JOA: 25
      patients had 100 scores, 5 patients had 95 to 99 scores, 3 patients had 90 to 94
      scores, 2 patients had the scores lower than 90. CONCLUSION: The manual reduction
      and external fixation with paper splints is easily handled, and it can increase
      the success rate of restoration steadily and safely.

PMID- 19108435
TI  - [Treatment of proximal fracture of humerus by percutaneous antegrade Kirschner
      pinning].
AB  - OBJECTIVE: To summarize and analyze the clinical indication, surgical techniques
      and results of percutaneous antegrade Kirschner pinning in the treatment of
      proximal fracture of humerus. METHODS: Thirty-two patients with displaced
      fractures of the proximal humerus were treated with 2 to 3 Kirschner wires by
      percutaneous antegrade transfixation. Among 32 casas, there were 7 male and 25
      female, with a mean age of 49.25 years (range, from 28 to 75 years). According to
      the Neer fracture classification, there were 20 cases of 2-part, 9 of 3-part, and
      3 of 4-part fractures. RESULTS: All patients were followed up for 8 to 34 months
      with an average of 13.5 months. According to Constant-Murley evaluation, the
      results were excellent in 21 cases, good in 9, fair in 2. CONCLUSION:
      Percutaneous antegrade transfixaton is a good technique for the management of
      displaced 2-part fractures of the proximal humerus and also alternative to 3-part
      or 4-part fractures.

PMID- 19108436
TI  - [Comparative study on the Pizhen and acupuncture for the treatment of
      supraclavicular nerve-entrapment syndrome].
AB  - OBJECTIVE: To investigate the clinical effects of Pizhen for the treatment of
      supraclavicular nerve-entrapment syndrome. METHODS: From March 2004 to April
      2006, among the 200 patients of supraclavicular nerve-entrapment syndrome, 100
      patients (75 patients were male and 25 patients were female, ranging in age from
      25 to 65 years, with an average of 45 years)were treated with Pizhen, 100
      patients (60 patients were male and 40 patients were female, ranging in age from
      16 to 63 years, with an average of 35 years) were treated with Acupuncture. The
      therapeutic effects of the two groups were compared. RESULTS: All the patients
      were followed up and the duration ranged from 6 to 12 months, 9.6 months in
      average. Among the patients in Pizhen group, 79 patients got an excellent result,
      12 good, 8 fair, and 1 poor, and the tension exponent of soft tissues decreased
      from preoperative 3.56 +/- 0.35 to postoperative 2.11 +/- 0.41. In the control
      group, 43 patients got an excellent result, 21 good, 17 fair, and 19 poor, the
      tension exponent of soft tissues decreased from preoperative 3.61 +/- 0.21 to
      postoperative 3.13 +/- 0.56. The therapeutic effects and tension exponent of soft
      tissue in the two groups had statistical differences (P < 0.05 and P < 0.01).
      CONCLUSION: The clinical effect of Pizhen is better than the the acupuncture for
      the treatment of supraclavicular nerve-entrapment syndrome. The therapy of Pizhen
      is safe, good and easily to practice.

PMID- 19108437
TI  - [Application of halo-pelvic distraction to the treatment of adult idiopathic
      scoliosis].

PMID- 19108438
TI  - [Pizhen therapy for the treatment of neck pain caused by cervical spondylosis: a
      report of 61 cases].

PMID- 19108439
TI  - [Treatment of mid-distal tibial shaft fractures with modified ilizarov external
      fixation].

PMID- 19108440
TI  - [Supination and pulling method for the treatment of vertebral artery type of
      cervical spondylosis: a report of 45 cases].

PMID- 19108441
TI  - [Minimally invasive diskectomy for the treatment of lumbar disk herniation].

PMID- 19108442
TI  - [Botulinum toxin A for the treatment of refractory external humeral
      epicondylitis: a report of 58 cases].

PMID- 19108443
TI  - [Application of long-segment pedicle screw fixation in upper-middle thoracic
      spine fracture and dislocation].

PMID- 19108444
TI  - [Effects of triamcinolone acetonide injected in C2 transverse process combined
      with haojishi ([Chinese characters: see text]) patch on cervicogenic headache].

PMID- 19108445
TI  - [Treatment of anterior dislocation of shoulder joint by bone setting manipulation
      at zero position].

PMID- 19108446
TI  - [Treatment of giant synovial chondroma at elbow joint: a report of 1 case].

PMID- 19108447
TI  - [Clinical advances of muscle status in osteoarthritis].
AB  - This article summarizes relevant clinical studies on muscle status and
      osteoarthritis. Evidence from many researches have implied the importance of
      muscle weakness, decreased muscle strength and muscle function as pathological
      factor in the process of osteoarthritis, and muscle should also be an effective
      target for the treatment of osteoarthritis. Further study need to be conducted
      from the angle of muscle to explore the mechanism of osteoarthritis and to
      develop new drugs.

PMID- 19108448
TI  - [The application advances of bisphosphonates in bone metastasis].
AB  - Bone metastases is a serious complication of patients with tumor. It is
      associated with substantial morbidity, including bone pain, pathological
      fracture,neurological deficit and (or) hypercalcemia. Thus, the management of
      bone metastasis is a clinically significant issue. Bisphosphonates have now
      become a part of standard therapy to treat and prevent skeletal-related events
      (SRE), it could inhibit osteoclast-mediated bone resorption and demonstrate
      antitumor activity in preclinical models. Bisphosphonates are the most effective
      agent for treating and (or) preventing complications of bone metastasis, reducing
      the incidence of skeletal-related events, and improving quality of life in
      patients with bone metastasis.

PMID- 19108449
TI  - [Research progression of tissue transplantation and functional reconstruction of
      spinal cord].
AB  - Functional reconstruction of injured spinal cord depends on its structure
      restoration,tissue transplantation is the most important strategy in medicine
      field at present. The tissue applied for transplantation including peripheral
      nerves, embryonic spinal cord, cellular transplantation and gene organization.
      However, the results exist dissension. The report overviews the status quo of
      tissue transplantation, intended to strengthen the recognition of treatment of
      spinal cord injury.

PMID- 19108450
TI  - [Elevation of the therapy level of hip fractures].

PMID- 19108451
TI  - [Retrospective study of comparing the different internal fixation methods in
      treating intertrochanteric fracture of femur].
AB  - OBJECTIVE: To investigate the selective strategy of the internal fixation methods
      in treating intertrochanteric femoral fracture by comparing the different
      methods. METHODS: Data of 326 cases of intertrochanteric femoral fractures
      treated with different internal fixation methods were concluded. One hundred and
      sixty-five cases were treated with the dynamic hip screws (DHS group), 78 male,
      87 female, age 38 to 98 years. One hundred and three cases were treated with the
      anatomical plates of proximal femur (AP group), 48 male, 55 female, age 39 to 89
      years. Fifty-eight cases were treated with the fixation expandable proximal
      femoral nails (PFN group), 31 male, 27 female, age 41 to 92 years. According to
      Evans classification of intertrochanteric femoral fractures, fractures were
      divided into type I, II, III, IV and retro-intertrochanteric type. The cases of
      each type of three groups were DHS(12, 35, 61, 42, 15); AP(9, 23, 38, 25, 8); PFN
      (6, 13, 21, 13,5). Data of each group was collected for statistical analysis on
      the following aspects: operation time,blood loss, fluoroscopy exposures,
      drainage, clinical healing time of fracture, post-operative restored function and
      the total complications. RESULTS: The difference of operation time, blood loss,
      fluoroscopy exposures, drainage, clinical healing time of fracture, post
      operative restored function were of statistical significance (P < 0.01). In
      comparing with group DHS and AP, group PFN was of less operation time, blood
      loss, drainage, clinical healing time of fracture, but more fluoroscopy
      exposures, and the post-operative restored function of group PFN was more
      satisfied. The difference of operative complications were of no statistical
      significance (P = 0.05). CONCLUSION: The fixation expandable proximal femoral
      nail is a good choice for intertrochanteric femoral fracture.

PMID- 19108452
TI  - [Application of modified lateral minimal incision technique for total hip
      arthroplasty].

PMID- 19108453
TI  - [Stress test and clinical application of the minimal-invasive dynamic hip screw].
AB  - OBJECTIVE: To recognize the effect of minimal-invasive dynamic hip screw (MIDHS)
      on the treatment of intertrochanteric fracture of the hip by biomechanical test
      and preliminary clinical application. METHODS: Ten artifical made
      intertrochanteric fractures of femoral specimen from five cadavers were divided
      into two groups randomly. The fractures in first group were fixed by MIDHS and
      other group were fixed by dynamic hip (DHS). Biomechanical characteristics of two
      different devices were compared with the biomechanical character of load
      straining, load-displacing, rigidity and strength of femur by statistic analysis.
      According to the Harris evaluation, healing effect of intertrochanteric fractures
      was evaluated clinically on the 15 cases. RESULTS: Straining changes of MIDHS
      were 14% and 11% less than that of DHS on the tensile side and the pressure side
      respectively; Sinking and horizontal displacement, were 19% and 22% less than
      that of DHS respectivly. But external and internal stress intensity,axial and
      bending rigidity were all higher than that of DHS, they were 12%, 11%, 19% and
      37%. Maximal destroyed twisting moment (15%) and average twisting rigidity (15%)
      were both higher than that of DHS, but twisting angle was 18% less. Under the
      force, of 1 800 N, the open angle of the fracture on transverse section was 2.28
      degrees,while the DHS's was 3.60 degrees . The data above were significant
      differences statistically (P < 0.01). The average Harris score of the 15 cases
      with intertrochanteric fractures treated by MIDHS was 91, excellent and good rate
      was 92.7%, without complications of internal fixation failure,postoperative
      infection and so on. CONCLUSION: The design of minimal-invasive dynamic hip screw
      is reasonable and effective against rotating, shearing and varus stress force of
      the fracture, and it provides possibility of implanting the internal fixation
      with minimal incision. So it is an ideal internal fixation device for the
      treatment of intertrochanteric fractures.

PMID- 19108454
TI  - [Reduction and fixation of fracture of pubic rami by inserting construction plate
      through the punctiform-incision approach].
AB  - OBJECTIVE: To observe the effect of pubic fractures reducted and fixed thorough
      the punctiform incision approach. METHODS: From 2002 to 2005, 10 cases with 18
      fractures of pubis rami (8 male and 2 female) were treated with inserting
      construction plate by the punctiform incision approach. The average age of these
      patients was 37.2 years (range, 24 to 56 years). The mean duration between injury
      and operation was 8.7 days (range, 4 to 14 days). RESULTS: Internal fixation for
      eighteen pubis fractures were accomplished by 28 punctiform incisions. The blood
      loss for each incision was averagely 30 ml, operation time of each pubic was
      about 45 minutes. Function restoration was evaluated by Majeed' score and all
      patients gained excellent result. CONCLUSION: The fracture of pubic rami can be
      fixed sucessfully by punctiform incision approach. It provides smaller incision,
      less postoperative complications and excellent function rehabilitation.

PMID- 19108455
TI  - [Closed reduction and percutaneous screw fixation for the treatment of calcaneal
      tuberosity fracture].

PMID- 19108456
TI  - [Complications of intertrochanteric fracture treated with dynamic hip screw:
      cause analysis and prevention].
AB  - OBJECTIVE: To analyze causes of the complications in treatment of the
      intertrochanteric fractures with dynamic hip screw (DHS) and discuss the way of
      the prevention. METHODS: Sixty-five cases of intertrochanter fractures of femur
      were treated with DHS. Among them, the complications occurred in 13 cases, their
      causes were analyzed and corresponding preventive treatments were discussed. The
      patients with complications included 8 male and 5 female, and the mean age was
      70.2 years (range, from 56 to 82 years). RESULTS: The major complications of 13
      cases included proximal femoral cortex broken in 2 cases, femoral heads
      penetrated by screw in 2,varus deformity of hip in 5, necrosis of femoral head in
      1, the wound infection in 3 (including bone non-union in 1). CONCLUSION: The main
      causes of the complications are various as follows: the nonstandard operative
      procedure, incorrect aseptic measures, unsatisfactory reduction, and too early
      weight bearing. Therefore, appropriate preventive measures such as correct
      aseptic manipulation, effective treatment of general medical illness,formal
      operative procedure good reduction, proper fixation of lesser trochanter and
      posteromedial bone fragment, and correct functional training program should be
      taken.

PMID- 19108457
TI  - [Treatment for ipsilateral fractures of the femoral neck and shaft].
AB  - OBJECTIVE: To investigate the curative effect of different internal fixation for
      ipsilateral fractures of the femoral neck and shaft. METHODS: By retrospective
      study of 27 patients who sustained ipsilateral femoral shaft and neck fractures
      from June 1993 to March 2004. There were 22 male and 5 female, with an average
      age of 35 years (range in 14 to 65 years). The femoral neck and shaft fractures
      were stabilized with dynamic hip screw system (DHS) in 3 cases,with dynamic
      compression plate and cannulated lag screw in 12 cases, with constructive nail in
      8 cases, with antegrade intramedullary locking nail and cannulated lag screw in 4
      cases. There were 13 cases used of the temporary fixation of Kirschner wire
      before the pexia of the femoral neck fractures. RESULTS: All of the patients were
      followed up for 36 to 75 months, with an average of 44 months. The average
      healing period of femoral neck fracture was 4.5 months in 25 cases, nonunion of
      femoral neck fractures in 2. The average healing period of femoral shaft fracture
      was 6 months in 27 cases. In 14 cases that not using temporary fixation of
      femoral neck with Kirschner wire, there were nonunion of femoral neck in 2 and
      slight coxa vara in 3. CONCLUSION: There are a wide choice of internal fixation
      method for treatment of ipsilateral fracture of the femoral neck and shaft, the
      fixation with dynamic compression plate and cannulated lag screw is a handy
      method. It would be avoided to the replacement and trauma, emporary fixing the
      fracture with Kirschner wire before the pexia of the femoral neck fracture.

PMID- 19108458
TI  - [Evaluation of diagnosing cervical vertigo with computerized static
      posturography].
AB  - OBJECTIVE: To provide a quantitative base for diagnosing cervical vertigo by
      establishing a biomechanics method. METHODS: From July 2004 to Nov 2005, the
      static posturography (SPG) of normal 86 health individuals and 75 patients with
      cervical vertigo were quantitatively measured and qualitative diagnosis
      respectively in closed and open eyes. There were 40 male and 46 female in health
      adults, ranging from 20 to 74 years old (mean 30 years). There were 16 male and
      59 female in vertigo patients, ranging from 20 to 74 years old (mean 44.5 years).
      In contrast to current diagnosis method of patients with cervical vertigo, the
      clinical value was evaluated. RESULTS: Under the state of closed eyes, the
      sensitivity of SPG diagnosing cervical vertigo was 76%; the specificity was 93%;
      the Youden index was 69%; the coincidence was 85.1%; the positive predictive
      value was 90.5%; the negative predictive value was 93%; the positive and negative
      likelihood ratio were 10.893 and 0.258 respectively. Under the state of open
      eyes, the sensitivity was 49.3%; the specificity was 87.2%; the Youden index was
      38.6%; the coincidence was 69.6%; the positive predictive value was 77.1%; the
      negative predictive value was 87.2%; the positive likelihood ratio was 3.857; the
      negative one was 0.581. Regardless of closed or open eyes, foreword-backward type
      shift orbit was the with cervical vertigo. CONCLUSION: The patients with cervical
      vertigo and normal individuals can be diagnosed objectively and quantitatively
      with SPG under the state of closed eyes, which can achieve the basic requirements
      of diagnosing cervical vertigo with validity, reliability and good clinical
      application. However, the rate of missed diagnosis with SPG under the state of
      open eyes is too high to meet the diagnostic needs.

PMID- 19108459
TI  - [Clinical comparison between micro-endoscopic discectomy (MED) and open
      discectomy for treatment of lumbar disc herniation].
AB  - OBJECTIVE: To compare between micro-endoscopic discectom) (MED) and open
      decompression discectomy, and assess the clinical value of MED. METHODS: Two
      hundreds and sixty-one cases who suffered from lumbar disc herniation had a
      retrospective study. One hundred and twenty-one of 261 patients were treated with
      MED including 72 male and 52 female with an average age of 37.6 years ranging 26
      to 63, the segment of herniated discs were at L4.5 in 66 and at L5S1 in 58. The
      other 137 patients were treated with decompression by fenestration and discectomy
      including 66 male and 71 female with an average age of 44.5 years ranging 25 to
      71, the segment of herniated discs were at L4.5 in 64 and at L5S1 in 73. MED was
      performed via a scopes. Open decompression discectomy was performed decompression
      by fenestration and discectomy. RESULTS: MED group were followed up for 14.5
      months on average, the operative time was (85 +/- 15) minutes and blood loss was
      (50 +/- 10) ml, time of laying in bed after operation was (50 +/- 8) hours. Open
      decompression group were followed up for 15.5 months on average, operative time
      was (60 +/- 15) minutes and blood loss was (80 +/- 20) ml, time of laying bed
      after operation was (150 +/- 24) hours. MED group needed significantly less
      narcotic medication after operation than open decompression group. According to
      modified Macnab criteria, the results were excellent in 94, good in 25, fair in 5
      in MED group and excellent in 101, good in 28, fair in 8 in open decompression
      group. CONCLUSION: As compared with open decompression group, MED offers a
      similar short-term clinical outcome, but with smaller incision, less tissue
      trauma and quicker recovery.

PMID- 19108460
TI  - [Percutaneous fixation and bone graft through small incision for treating
      extension distal fracture of radius].

PMID- 19108461
TI  - [Biomechanical evaluation of three-dimensional stability of anterior approach
      screw fixation through C2 vertebral body to C1 lateral mass].
AB  - OBJECTIVE: To determine the three-dimensional stability of C1-C2 after anterior
      approach screw fixation through C2 vertebral body to C1 lateral mass for C1-C2
      instability or dislocation. METHODS: The three-dimensional range of motion of
      atlantoaxial joint were measured in 16 human cadaveric specimens under four
      conditions: the intact state (1st group), odontoid fracture of type II (2nd
      group), instrumentation with posterior C1-C2 trans-articular screw fixation
      (Magerl technique) (3rd group) and anterior approach screw fixation through C2
      vertebral body to C1 lateral mass (4th group) respectively. RESULTS: There was
      generally significant difference between 1st group and other groups and between
      2nd group and other groups by statistics analysis (P < 0.001). Range of motion
      significantly decreased in 3rd group and 4th group in all directions. There was
      generally no significant difference between the two methods by statistical
      analysis (P > 0.05). CONCLUSION: Anterior approach screw fixation through C2
      vertebral body to C lateral mass provides satisfied stability. It provides the
      equivalent effect to Magerl technique. It is a kind of reliable surgery choice
      for the treatment of instability or dislocation of C1-C2 joint.

PMID- 19108462
TI  - [In vivo effects of Qizheng-xiaotong plaster on soft tissue injury of rabbit
      ears].
AB  - OBJECTIVE: To explore in vivo effects of Qizheng-xiaotong plaster on soft tissue
      injury in rabbit ears at different periods and to offer theoretical bases for
      clinical application. METHODS: The experimental models of soft tissue injury in
      ears were produced in 10 New Zealand white rabbits, and the ears were divided
      into three groups at the 1st, 2nd, 3rd week. The normal group and treatment group
      were given the Qizheng-xiaotong plaster extract, and the model group with normal
      saline. Microscopic analysis, digital collection system, infrared temperature
      tester and thickness tester were applied to determine the changes of soft tissue
      injury in local microcirculation and the temperature change after 0, 0.5, 3 and 5
      hours, and swelling change at 1 to 5 days respectively. RESULTS: At the 3rd hour,
      blood velocity speeded up in normal group and model group, and it lasted for two
      hours in model group. As compared with model group, it slowed down to original
      level in treatment group at the 5th hour and the soft tissue swelling decreased
      from the 3rd to the 5th day as well. CONCLUSION: The application of Qizheng
      xiaotong plaster is effective in preventing further soft tissue oedema and
      haematoma. It can make the soft tissue swelling decreased at chronic stage
      compared with that at acute stage.

PMID- 19108463
TI  - [Treatment of floating elbow injuries by internal and external fixation and
      traditional Chinese herbs].

PMID- 19108464
TI  - [Therapeutic effects of multi-stage manipulative reduction and splint fixation in
      22 patients with tibia shaft fracture].
AB  - OBJECTIVE: To study the method and effects of multi-stage manipulative reduction
      and homemade splint fixation in the treatment of tibia shaft fractures. METHODS:
      Twenty-two patients (16 male and 6 female) were involved the retrospective study.
      The average age was 33 years (from 6 to 54 years). Single tibia shaft fracture
      was in 15 cases and tibiofibular fracture in 7 cases. Fracture site: 3 cases were
      in the upper part of the tibia, 4 in the middle part and 15 in the lower part.
      Fracture pattern: oblique fracture was in 8 cases, spiral fracture in 5 cases,
      comminuted fracture in 4 cases and transverse fracture in 5 cases. All the
      patients were treated with multi-stage manipulative reduction and homemade splint
      fixation. RESULTS: All the patients were followed up from 3 to 15 months (mean 6
      on months). There were malunion of fracture in 1 case, delayed union in 1 case
      and nonunion in 1 case. The results were excellent in 18 cases, good in 3 cases
      and poor in 1 case according to WANG Xu-dong assessment criteria. CONCLUSION: On
      the base of traditional manipulative reduction and splint fixation, multi-stage
      manual correction could stabilize the broken part and prevent displacement. It
      had the characteristics of easy operation, reliable fixation, rapid union of
      fracture, few complications and influences on joint function. Multi-stage
      manipulative reduction and homemade splint fixation is one of the most reliable
      methods for closed tibia fracture.

PMID- 19108466
TI  - [Experiment study of alendronate in the prevention and treatment of aseptic
      loosening of prosthesis].
AB  - OBJECTIVE: To investigate the effect of alendronate on the prevention and
      treatment of aseptic loosening of prosthesis. METHODS: A rat model of particle
      induced osteolysis was used. Thirty-xis SD rats were divided into three groups:
      negative control group, positive control group and experiment group. Alendronate
      was administered by ig in experiment group. Positive control group and experiment
      group received intro-articular injections of ultrahigh molecular weight
      polyethylene (UHMWPE) particles at 4, 6, 8, 10 weeks postoperatively. Negative
      control group was received injection with mixture solution of mouse serum and PBS
      only. All animals were sacrificed at 12 weeks after operation for histologic
      examination. In vitro human peripheral blood mononuclear (PBMC)were separated and
      cultured and divided into five groups as group A: PBMC group, group B: PBMC and
      particles,group C:PBMC and particles with 10(-4) mol/L alendronate, group D:PBMC
      and particles with 10(-5) mol/L alendronate, group E: PBMC and particles with 10(
      6) mol/L alendronate. The production of IL-1beta, IL-6, TNF-alpha in each group
      were tested. RESULTS: Alendronate could prevent particle-induced osteolysis. The
      production of IL-1beta, IL-6, TNF-alpha was inhibited when alendronate was used.
      CONCLUSION: Alendronate can inhibit bone absorptive factors expression induced by
      wear particles and may be used in the prevention and treatment of aseptic
      loosening of prosthesis.

PMID- 19108465
TI  - [Study of inducing bone marrow-derived mesenchymal stem cells into chondrocytes
      in vitro].
AB  - OBJECTIVE: To explore a method of isolation, culture and chondrogenic phenotype
      differentiation of mesenchymal stem cell (MSCs) from the bone marrow of rats in
      vitro and to offer experimental reference for the resources of seeding cells in
      cartilage tissue engineering. METHODS: MSCs were isolated from bone marrow and
      purified by density gradient centrifuge and cultured in vitro. The MSC adherence
      formed and those in passage 3 were chosen to induce into chondrogenic
      differentiation. After 7, 14, 21 days, immunohistochemical techique was applied
      to detect the expression of collagen type II. The differentiated cells were
      implanted on the CPP/PLLA composites. After the cell-scaffold complex was
      cultured in vitro for one week, the ultrastructure of the scaffold was observed
      with scanning electron microscopy. RESULTS: The differentiated cells changed from
      a spindle-like fibroblastic appearance to a polygonal shape, the capability of
      proliferation was down markedly. Immunohistochemical staining of collagen II were
      positive for the pass age, especially in the 21st days. Induced MSCs were well
      adherent to the scaffold composites and the cells were embedded by the cell
      matrix. CONCLUSION: Under the induced medium, MSCs can differentiate into
      chondrogenic phenotype and secrete specificity matrix of cartilage in vitro. MSCs
      can likely be served as optimal cell source for cartilage tissue engineering.

PMID- 19108467
TI  - [Analysis of differentiation characters in osteosarcoma Mdr sublines].
AB  - OBJECTIVE: To explore the relationship between multidrug resistance (Mdr) and
      malignancy. To observe whether P-glycoprotein (P-gp) overexpression had the same
      bioactivity as osteogenic stem cell turning into more mature cell or more complex
      phenotype when parent cell line turned to Mdr phenotype. METHODS: Six cell
      sublines of Mdr phenotype with different expression degree were analyzed.
      Stathmin generally identified in malignancy cell and stem cell, was a microtubule
      associated protein and the signal of differentiation in osteogenic stem cell. RT
      PCR and hybridization in situ were used to analyze the relationship between Mdr1
      mRNA and expression of Stathmin mRNA and VEGF mRNA. RESULTS: Morphological and
      functional analysis of Mdr phenotype showed the P-gp-positive cell lines were
      more differentiated than the parent cells in terms of enhanced activity of
      cellular alkaline phosphatase. These subclones all displayed a decrease in
      potential malignancy such as tumor growth rate and metastatic ability. A
      significant negative correlation could be identified between Mdr1 mRNA and
      expression of VEGF and Stathmin mRNA. CONCLUSION: Expression of Mdr1/P170
      indicated osteosarcoma cells differentiated towards more mature state, which will
      develop the new research field of Mdr and supply the new research method of the
      function of P- gp.

PMID- 19108468
TI  - [Small incision decompression in surgical treatment of leg fracture].

PMID- 19108469
TI  - [A case report of plasma cell granuloma in the sternum].

PMID- 19108471
TI  - [Treatment of infected bone defect with one stage open cancellous bone grafting].
AB  - OBJECTIVE: To explore the feasibility of the treatment of infected bone defect
      with one stage open cancellous bone grafting and summarize the key factors
      improving the curative effects. METHODS: Twelve cases of infected bone defects
      were reviewed, which involved 8 male and 4 female with an average age of 42 years
      (range, 22 to 68 years). The study consisted of 7 cases of calcaneal defects, 4
      tibial defects and 1 femoral defect. The procedure included dressing change,
      resection of the devitalized soft tissue and bone tissue. After the debridement,
      the bone defect at one stage was treated with cancellous bone grafting and the
      wound was open. The wound was closed with skin transplantation when it was
      covered by granulation tissue completely. RESULTS: The wound was covered with
      granulation tissue in the average 24.1 days after operation and was closed in the
      average 30.3 days. All the patients were followed up for 8 to 30 months with an
      average time of 18 months. All the bone defects were healing after bone grafting
      and there was no infection recurrence. CONCLUSION: One stage open cancellous bone
      graft is an easy and feasible treatment for infected bone defect. Resecting of
      the devitalized tissue before operation, radical debridement, enough bone graft
      in operation and careful dressing change after operation are all the key factors
      to acquire the satisfactory outcome.

PMID- 19108470
TI  - [Repair of scalp defect using V-Y-S rotation flap].
AB  - OBJECTIVE: To report the clinical results of scalp defect using V-Y-S rotation
      flap. METHODS: From March 2003 to October 2005, 5 cases scalp defect (4 male, 1
      female) were reconstructed with the technique. The age ranged from 26 to 52 years
      (mean 32 years). The scalp defect ranged from 3 cmx3.5 cm to 4 cmx5 cm. Four
      cases were reconstructed with bilateral flap and one case was reconstructed with
      unilateral flaps. RESULTS: All patients were followed-up from 10 to 42 months
      (mean, 28 months). All the flaps survived completely and showed good hair growth
      and had satisfactory clinical results. CONCLUSION: Repair of scalp defect using V
      Y-S rotation flap technique is simple with no need for a skin graft and can be
      performed quickly, there is minimal morbidity and the outcome is highly
      successful.

PMID- 19108472
TI  - [Application of skin and soft tissue distraction technique for defect of skin and
      soft tissue].
AB  - OBJECTIVE: To investigate the repair of skin and soft tissue defect by skin and
      soft tissue distraction tecnique and evaluate clinical results. METHODS: Twenty
      five patients with skin and soft tissue defect were repaired by skin and soft
      tissue distraction technique including 16 male and 9 female. The age ranged from
      8 to 66 years with an average age of 29.3 years. Parallel Kirschner wires were
      inserted through the defect skin margin at the interval of every 0.5 to 1.5 cm,
      the Kirschner wire was gradually drawed to the close by thick silk thread or tiny
      steel-wire, the defect of skin and soft tiuuse was closed from two sides and the
      wound disappeared. RESULTS: The wounds of 15 patients were anastomosed dircetly
      through skin and soft tissue distraction for 20 to 60 minutes, other ten wounds
      were anastomosed from 3 to 26 days, all healed well. By the follow up from 2 to
      26 months, the wound skin looked as line scar, corresponding to the result of
      common debridement anastomosis. CONCLUSION: Skin and soft tissue distraction
      tecnique can not replace skin grafting, flap transferring and flap grafting. But
      it may avoid damage to the supply area and the risk of flap necrosis. Skin and
      soft tissue distraction tecnique is a good method to repair skin and soft tissue
      defect.

PMID- 19108473
TI  - [Early diagnosis and microsurgical treatment of hand glomus tumor in 30 female
      cases].
AB  - OBJECTIVE: To investigate the clinical features, early diagnosis and surgical
      treatment of the hand glomus tumor in the female. METHODS: Thirty female patients
      with the hand glomus tumor underwent early resection by microsurgery. The average
      age was 35 years ranging from 18 to 48 years. The course of disease was from 3
      months to 3 years. All patients' tumors occured on single finger. RESULTS: In the
      30 cases, there were 28 patients with localized eminences and hepatic plaques
      under the nail. The compression of distal phalanx could be seen on radiographs in
      18 patients, definite and localised tenderness on nails could be found in all
      cases, the tenderness disappeared and no recurrence after 15 months of follow-up
      in all cases. CONCLUSION: The hepatic plaque under the nail and fixed tenderness
      point on the nail are of significance in diagnosis for the hand glomus tumor in
      the female, the early microsurgical resection is unique effective treatment to
      this disease.

PMID- 19108474
TI  - [Clinical investigation of conservative treatment for volar Barton fracture].
AB  - OBJECTIVE: To discuss the indication and outcome of volar Barton fracture treated
      by nonoperative method. METHODS: Twenty-three cases of volar Barton fracture
      treated by closed method included 8 male and 15 female with an average age of
      52.2 years,ranging 16 to 84 years. Among them, 16 cases showed subluxation of the
      carpus (15 cases were Mehara type I ,1 case was Mehara type III) by radiographs
      except the other 7 cases. By the experimentation in 32 cadavers, the injury of
      dorsal radiocarpal ligament was supposed to be a very important cause of the
      subluxation of the radiocarpal joint. The criteria of Pattee and Thompson was
      used to evaluate the outcome of the treatment. RESULTS: Twenty-three patients
      were followed up for 7 to 70 months, 11 cases gained satisfactory outcome (1 case
      as excellent, 10 cases as good), 12 cases gained unsatisfactory outcome (5 cases
      as fair, 7 cases as poor). Five of 7 cases without the subluxation of the carpus
      by the radiographs gained satisfactory outcome. Six of 16 cases with the
      subluxation of the carpus gained satisfactory outcome. CONCLUSION: (1) The result
      of reduction will influence the outcome of the treatment, the step on articular
      surface shoud be less than 2 mm after reduction. (2) Nonoperative method is
      recommended if volar Barton fractures are not associated with subluxation of the
      carpus. (3) Nonoperative method can be tried first if the fractures associated
      with the subluxation of the carpus, however operation is recommended when the
      articular step is more than 2 mm.

PMID- 19108475
TI  - [Evaluation of imaging diagnosis of stress fracture].

PMID- 19108476
TI  - [Replacement of humeral head prosthesis for four-part proximal humeral fractures
      or fracture-dislocations].
AB  - OBJECTIVE: To evaluate the short-term results of humeral head replacement for the
      treatment of four-part proximal humeral fractures or fracture-dislocations.
      METHODS: Twenty-five patients (11 male and 14 female)with four-part proximal
      humeral fractures or fracture-dislocations underwent humeral head replacement.
      The average age was 68.2 years (ranging from 56 to 77 years). All cases were
      followed up and evaluated the clinical results including pain, function and range
      of motion of shoulder with Neer scoring system. RESULTS: The follow-up ranged
      from 12 to 40 months with an average time of 29.3 months. No prosthesis
      loosening, prosthesis dislocation, postoperative infection, nerve injury or
      periprosthesis fractures occurred. The results were excellent in 8 cases, good in
      11 cases and fair in 6 cases. The excellent and good rate was 76% according to
      Neer scoring system. CONCLUSION: Replacement of humeral head prosthesis could
      attain good short-term results for four-part proximal humeral fractures or
      fracture-dislocations. The key to improve the postoperative results is meticulous
      surgical techniques and appropriate correct consecutive physical therapy.

PMID- 19108477
TI  - [Therapy of sprained ankle with the theory of relative fixation and fairly
      activity].

PMID- 19108478
TI  - [Preliminary report for treatment of discogenic low back pain with combined
      percutaneous laser and O2-O3 mixture].
AB  - OBJECTIVE: To evaluate the efficacy of percutaneous laser and O2-O3 mixture in
      treating chronic discogenic low back pain. METHODS: There were 48 patients
      included 32 male and 16 female with the mean age of 43.5 years (range, from 21 to
      66 years). The duration of symptoms was more than 6 months, all patients were
      treated with percutaneous laser and O2-O3 mixture under TV monitoring. RESULTS:
      Forty-eight patients followed-up showed no severe complications. At 1 week follow
      up, 8 cases were evaluated as excellent, 28 as good, 8 as fair and 4 as poor by
      Macnab standard. The excellent and good rate reached 75%. At 3 months follow up,
      17 cases were evaluated as excellent, 23 as good, 6 as fair and 2 as poor with
      the excellent and good rate of 83.3%. At 6 months follow up, 20 cases were
      evaluated as excellent, 22 as good, 4 as fair and 2 as poor with a total
      effective rate of 87.5%. At 12 months follow up, 21 cases were evaluated as
      excellent, 22 as good, 4 as fair and 1 as poor with a total effective rate of
      89.6%. CONCLUSION: Combined percutaneous laser and O3-O3 mixture is an effective
      and safe method in treating discogenic low back pain.

PMID- 19108479
TI  - [Experimental studies on the effect of Xianzhen decoction on the bone density and
      biomechanics in ovariectomized].

PMID- 19108480
TI  - [Manipulation treatment of old dislocation of elbow joint].

PMID- 19108481
TI  - [Osteogenetic effect of mechanical vibration on bone].
AB  - Mechanical loading is the main "instructive" factor of bone formation. The
      mechanism becomes the heat point in the field of bone science, biomedicine
      project and rehabilitation research. Mechanical vibration is one of the mechanic
      stimulation. Evidences show that vibration has obvious anabolic effect, and will
      have a broad landscape in the treatment of osteoporosis. But in the present
      studies, there were incorporated with the vibration frequency, and intensity, in
      particularly, few reports about the mechanism of vibration to bone. It will
      provide theoretic foundation for further systematic, sound research and its
      clinical application.

PMID- 19108482
TI  - IUPS Congress: an important event for physiologists of the world.

PMID- 19108483
TI  - Looking for inspiration? Kyoto is the place to be in the summer, 2009.

PMID- 19108484
TI  - [Education in anatomy initiated by Pompe van Meerdervoort].
AB  - Pompe van Meerdervoort arrived at Nagasaki port on September 21, 1857 and started
      his western-style medical education for the first time in the Nishiyakusho of
      Nagasaki on November 12, 1857. He had 12 students including Ryojun Matsumono. The
      curriculum was largely based on that of Utrecht Army Medical School, which was re
      organized after 1841 and very good in balance of theory and practice. Among
      subjects, much attention was paid for Anatomy which was quite advancing at the
      time and in fact the lecture was given on every Tuesday, Thursday and Saturday
      morning from 1857 to the end of 1859. His lecture note on Anatomy was based on
      Handboek der Ontleedkunde van den Mensch originally written by C. E. Bock, which
      was translated into Dutch by P. H. Pool. The note currently available is a copy
      by the students. In Europe of those days, microscopes were developed and
      "Histology" had been established as a new science. Therefore, his lecture
      contained details of histological findings and now we can appreciate his policy
      to think much of Anatomy in the introduction of western-style medical education.

PMID- 19108485
TI  - [Historical development of modern anatomical education in Japan].
AB  - The medical schools in the beginning of Meiji era were diverse both in the
      founders and in the way of education, frequently employing foreign teachers of
      various nationalities. In 1871, German teachers were appointed to organized
      medical education at the medical school of the university of Tokyo. The
      anatomical education in the school was conducted by German teachers, i.e. Miller
      (1871-1873), Donitz (1873-1877), Gierke (1877-1880) and Disse (1880-1885),
      followed by Koganei who returned from the study in Germany. In 1882 (Meiji 15th),
      the general rule for medical school was enforced so that the medical schools were
      practically obliged to employ numbers of graduates of the university of Tokyo. In
      1887 (Meiji 20th), the educational system was reformed so that many of the
      medical schools were closed, and the medical schools were integrated into one
      university, five national senior high schools and three prefectural ones in
      addition to four private ones. After that most of anatomical teachers were either
      graduates of the university of Tokyo or those who studied in the anatomical
      department of the university. Before 1877 (Meiji 10th), the anatomical books were
      mainly translated from English books, and foreign teachers of various nationality
      were employed in many medical schools in Japan. After 1877 (Meiji 10th), the
      anatomical books based on the lectures by German teachers at the university of
      Tokyo were published. The anatomical books after 1887 (Meiji 20th) were written
      based on German books, and the German anatomical terms were utilized. After 1905
      (Meiji 38th), the original Japanese anatomical books appeared, employing
      international anatomical terms. At the first meeting of Japanese Association of
      Anatomists in 1893 (Meiji 26th), the Japanese anatomical teachers met together
      and most of them were graduates of the university of Tokyo or fellows of its
      anatomical department.

PMID- 19108486
TI  - [Achievements in anatomy education by Dr. Otto Mori in Taiwan].
AB  - My grandfather, Otto Mori (1980-1967) was one of the founders of anatomy
      education in Japan from 1940s to 1960s. While he was the director of Department
      of Medicine of Taipei Imperial University, he made efforts to establish the
      medical and anatomical education in Taiwan. Introduction of the achievement of
      anatomy education in Taiwan is important to know the history of anatomy education
      in Japan. I visited Taiwan National University (former Taipei Imperial
      University) in 2005, which was 60 years after Otto Mori started his life as a
      professor in Taiwan, and 110 years after Rintaro (Ogai) Mori, my great
      grandfather stayed shortly in Taiwan after Japan-China War. After the World War
      II, there has been very few opportunity of communication between anatomy labs of
      Taiwan and Japan. In Taiwan, more than 70 years ago, Japanese style anatomy
      education was established, however, after the WW II, they learned education style
      from the U.S. Chiba University exchange "sister universities" agreement between
      National Taiwan University in 2007, and started exchange communication regarding
      anatomy education and scientific research. It is meaningful to learn from
      excellent education system of old Japan when we communicate with National Taiwan
      University.

PMID- 19108487
TI  - [Study of Japanese anatomical terms, such as 'sphenoid bone'].
AB  - Japanese anatomical terms (butterfly-shaped bone) have an interesting history.
      Galen named a bone (wedge-like). This Greek term was introduced into Latin
      anatomical texts by transcribing into 'os sphnoides' or translating it as 'os
      cuneiforme'. Both terms mean equally wedge-like bone. From 16th century on, these
      two terms prevailed in European anatomical textbooks, but in 18th century some
      anatomists merged this bone with some kinds of winged creatures and named their
      wings "Ala major' and 'Ala minor'. In mid-19th century English-Chinese anatomical
      book, this bone was named (butterfly bone) by a medical missionary Benjamin
      Hobson. This term was introduced into Japanese textbooks. In Meiji Era both terms
      were used in Japanese textbooks, and (wedged-like bone). Some anatomists insisted
      on using because this echoed original Latin term's sense. Eventually, Japanese
      Associations of Anatomists adopted in 1943.

PMID- 19108488
TI  - [Establishment of anatomical terminology in Japan].
AB  - The history of anatomical terminology in Japan began with the publication of
      Waran Naikei Ihan-teimo in 1805 and Chotei Kaitai Shinsho in 1826. Although the
      establishment of Japanese anatomical terminology became necessary during the
      Meiji era when many western anatomy books imported into Janan were translated,
      such terminology was not unified during this period and varied among translators.
      In 1871, Tsukumo Ono's Kaibogaku Gosen was published by the Ministry of
      Education. Although this book is considered to be the first anatomical glossary
      terms in Japan, its contents were incomplete. Overseas, the German Anatomical
      Society established a unified anatomical terminology in 1895 called the Basle
      Nomina Anatomica (B.N.A.). Based on this development, Kaibogaku Meishu which
      follows the BNA, by Buntaro Suzuki was published in 1905. With the subsequent
      establishment in 1935 of Jena Nomina Anatomica (J.N.A.), the unification of
      anatomical terminology was also accelerated in Japan, leading to the further
      development of terminology.

PMID- 19108489
TI  - [History of Japanese Committee for Anatomical Nomenclature].
AB  - This paper records a history of the Japanese Committee of Anatomical Nomenclature
      since 1990, as a supplement to the previous report (1991), explains a progressing
      of the edition of Japanese medical terms by the Japanese Association of Medical
      Sciences and the Ministry of Education, Sciences and Culture, and points out of
      some problems on terms in Japanese.

PMID- 19108490
TI  - [Curve-fits with hybrid logistic functions for isovolumic left ventricular
      pressure curve and isometric myocardial tension curve].
AB  - Non-linear regression and curve-fitting may contribute to resolution of the
      mechanism, summarise information, remove noise, allow speculation regarding
      unmeasured data, and separate the effects of multiple factors. The isovolumic
      left ventricular (LV) pressure curve and isometric myocardial tension curve have
      been curve-fit with polynomial expotential and sinusoidal functions. The
      isovolumic LV pressure curve and myocardial isometric tension curve are composed
      of contraction and relaxation processes. We have proposed that hybrid logistic
      (HL) functions, calculated as the difference between two logistic functions, fit
      better the isovolumic LV pressure curves at any LV volume, heart rate, and
      infused calcium (Ca2+) concentration in coronary artery in the excised, cross
      circulated canine heart, and the isometric twitch tension curves at any muscle
      length and extracellular Ca2+ concentration in the ferret right ventricular (RV)
      papillary muscle. We suggest that the six HL parameters are useful to evaluate
      the contraction and relaxation processes in the heart and myocardium. This HL
      approach for the isovolumic LV pressure curves and the isometric twitch tension
      curves may provide a more useful model for speculating Ca2+ handling, Ca(2+) 
      Troponin C interaction, and cross-bridge cycling.

PMID- 19108491
TI  - [Comparison of three kinds of less invasive cardiac output measuring systems in
      aged patients].
AB  - BACKGROUND: Recently, the number of operations for aged patients have been
      increasing. They usually have various preoperative complications especially
      cardiovascular systems, and cardiac output measuring under general anesthesia is
      useful for their operative managements. The aim of this study was to compare the
      accuracy of three kinds of less invasive equipments for cardiac output
      measurements, i.e. the impedance cardiography (ICG), the partial CO2 rebreathing
      (NICO), and the arterial pressure-based cardiac output (APCO). METHODS: Subjects
      are 40 patients over 65 years of age scheduled for elective lower abdominal or
      surface surgery. During anesthesia, three kinds of cardiac output measuring
      systems obtained cardiac output simultaneously every five minutes. RESULTS: Both
      bias and percentage error between APCO and NICO were the smallest. There were
      statistically significant correlations between ICG and NICO, NICO and APCO, and
      APCO and ICG. Accuracy of the three kinds of cardiac output measuring systems was
      confirmed in this study. Although when arterial pressure was above 100 mmHg
      cardiac output values were reliable, values were not reliable below 100 mmHg. The
      four factors i. e. age, blood pressure level, history of hypertension and body
      structure effected cardiac output measurements. There was no statistic
      relationship between arterial pressure and cardiac output in all measurements.
      CONCLUSIONS: Three kinds of less invasive cardiac output measurement systems have
      enough functions to use during surgery for aged patients.

PMID- 19108492
TI  - [Multiple linear regression analysis for predictability of the extent of spinal
      anesthesia by plain bupivacaine].
AB  - BACKGROUND: Predictability of the extent of spinal anesthesia by plain
      bupivacaine has been controversial. METHODS: Two hundred and twenty-eight
      patients undergoing elective surgery with spinal anesthesia were enrolled in this
      retrospective study. Using gender, age, height, body mass index (BMI), chosen
      spinal interspace for spinal tap (L2-3 or L3-4), and dose of plain bupivacaine as
      independent variables, we performed stepwise multiple linear regression analysis
      to examine predictability of the extent of sensory blockade produced by spinal
      anesthesia using plain bupivacaine. RESULTS: Following equation was obtained.
      Extent of sensory blockade = 14.9 + (male : 0.540, female: -0.540) -0.0774 x
      height + 0.124 x BMI + (L2-3 : 0.345, L3-4: -0.345): r2 = 0.0604. P values of
      gender, height and BMI were less than 0.05; however, r2 of each variable was very
      low. CONCLUSIONS: Results of this retrospective study imply the unpredictability
      of the extent of spinal anesthesia produced by plain bupivacaine.

PMID- 19108493
TI  - [Comparison of the Pentax-AWS and Fineview video laryngoscopes in the ease of
      laryngoscopy in 50 patients].
AB  - BACKGROUND: We compared the Pentax-AWS and Fineview video laryngoscopes in the
      ease of laryngoscopy in 50 patients. METHODS: Preoperatively, the view of the
      pharynx (Mallampati score), the thyromental distance and the inter-incisor
      distance at opening the month were assessed. After induction of anesthesia and
      neuromuscular blockade, the two devices were inserted in turn in a randomized
      order. The views of the glottis (Cormack and Lehane classification) was compared
      between the two devices. RESULTS: Mallampati score was 3 in one patient; the
      thyromental distance was less than 6 cm in 5 patients; and the inter-incisor
      distance was less than 4 cm in 2 patients. With the Pentax-AWS, the view of
      glottis was always grade 1, whereas with the Fineview, the view was grade 1 in 36
      patients, grade 2 in 13 patients and grade 3 in one patient. The view was
      significantly better with the Pentax-AWS compared with the Fineview (P < 0.001).
      CONCLUSIONS: We conclude that the view of the glottis obtained using the Pentax
      AWS was significantly better than the view obtained with the Fineview.

PMID- 19108494
TI  - [Effects of rikkunshito on the postoperative nausea and vomiting (PONV) after
      laparoscopic gynecological surgery].
AB  - BACKGROUND: Postoperative nausea and vomiting (PONV) is one of unignorable
      complications after general anesthesia. The aim of this study was to examine
      prophylactic effects of TSUMURA rikkunshito (TJ-43), a herbal medicine consisting
      of eight herbs, on PONV after laparoscopic surgery. METHODS: One hundred and
      forty-two female patients undergoing gynecological laparoscopic surgery (ASA-PS1
      2) were randomly allocated to one of two groups receiving rikkunshito (n = 91)
      and control (n = 51). The oral administration of 2.5 g of TJ-43 was commenced the
      night before surgery and was continued for 3 days after surgery. The suppository
      form containing 1.5 g of TJ-43 was used during surgery. RESULTS: There were no
      significant differences of the incidence of PONV between the two groups. The
      patterns of change in the degree of PONV were similar between the two groups,
      although TJ-43 group showed slightly earlier reduction in symptom scores. The
      patients with TJ-43 showed earlier postoperative recovery of oral meal intake.
      CONCLUSIONS: Perioperative administration of TJ-43 showed a possible
      effectiveness to reduce the severity of PONV and to promote earlier recovery of
      oral meal intake after gynecological laparoscopic surgery.

PMID- 19108495
TI  - [Remifentanil for awake craniotomy].
AB  - We report two cases of awake craniotomy successfully managed using remifentanil.
      During the intraoperative awake period lasting 2 to 2.5 hours, the infusion of
      low doses of remifentanil (0.02-0.05 microg x kg(-1) min(-1)) with or without
      propofol kept the patients comfortable and sufficiently awake to conduct various
      tasks but did not produce excessive respiratory depression. Because remifentanil
      can be titrated rapidly due to its extremely short duration of action, it may be
      useful for awake craniotomy for which both analgesia and sedation have to be
      tuned carefully according to the patient's need.

PMID- 19108496
TI  - [Second-degree atrioventricular block (Mobitz type II) probably exaggerated by
      dopamine during anesthetic management for a patient with ochronosis: a case
      report].
AB  - Ochronosis is a rare disease. Usually symptoms appear in the third, fourth, or
      later decade of life. The most common symptom is arthropathy, but cardiovascular
      system can be involved in this disease. A 71-year-old man with ochronosis was
      scheduled for total hip arthroplasty. Preoperatively, echocardiogram revealed
      aortic valve stenosis, mitral valve stenosis, and hypokinesis on antero-septal,
      lateral and posterior walls. Coronary angiogram revealed 50-75% stenosis of the
      left anterior descending coronary artery (segment 7) and 100% stenosis of the
      left circumflex artery (segment 15). Before the induction of general anesthesia,
      electrocardiogram showed first-degree atrioventricular block. After the induction
      of general anesthesia, blood pressure decreased markedly. Phenylephrine
      administration and rapid infusion of extracellular fluid failed to increase blood
      pressure. Thus, we started to administer dopamine at an infusion rate of 10
      microg x kg(-1) x min(-1) which increased blood pressure effectively, but
      electrocardiogram showed second-degree atrioventricular block (Mobitz type II).
      We started rapid infusion of a plasma substitute, and gradually decreased the
      infusion rate of dopamine to 4 microg x kg(-1) x min(-1). Then electrocardiogram
      returned to first-degree atrioventricular block. We estimated that second-degree
      atrioventricular block in this patient might have been exaggerated by dopamine at
      least in part.

PMID- 19108497
TI  - [Severe hypotension as a complication of intramyometrial injection of
      vasopressin: a case report].
AB  - A thirty-year-old woman was scheduled for laparoscopic myomectomy. After
      insertion of an epidural catheter at the L4-5 interspace, general anesthesia was
      induced with thiopental 250 mg followed by vecuronium 8mg intravenously to
      facilitate tracheal intubation. General anesthesia was maintained with
      sevoflurane and nitrous oxide. Just after intramyometrial injection of
      vasopressin, blood pressure decreased from 122/66 to 45/25 mmHg, and heart rate
      decreased from 52 to 45 beats x min(-1). The patient was ventilated with 100%
      oxygen, and we administered atropine 0.25 mg and ephedrine 16 mg intravenously.
      Blood pressure increased to 150/100 mmHg and heart rate increased to 135 beats x
      min(-1). Since electrocardiogram showed ST-segment depression and premature
      ventricular contraction, we administered nicorandil 3 mg followed by continuous
      infusion at a rate of 3 mg x hr(-1), and lidocaine 60 mg, intravenously. The ST
      depression and premature ventricular contraction disappeared immediately. To
      decrease blood pressure and heart rate, we increased inspiratory concentrations
      of sevoflurane and nitrous oxide and administered local anesthetics via epidural
      catheter, and hemodynamic parameters became gradually stable. We estimate that
      severe hypotension observed in this case is associated with intramyometrial
      injection of vasopressin. Increased blood concentration of vasopressin might
      cause vasoconstriction of coronary artery, increases in afterload, and/or direct
      myocardial depression resulting in decreased cardiac output.

PMID- 19108498
TI  - [Case of Staphylococcus epidermidis endocarditis with a bacterial vegetation
      suspected by intraoperative alternating pulse].
AB  - We report here a case of Staphylococcus epidermidis endocarditis with bacterial
      vegetation which was suspected by intraoperative alternating pulse on arterial
      pressure monitoring. A 65-year-old man was diagnosed as lumbar spinal canal
      stenosis and scheduled for operation. Preoperatively, he had chronic renal
      failure, mild aortic valve stenosis, and moderate mitral valve regurgitation.
      Neither inflammatory signs nor vegetations on TEE were observed preoperatively.
      General anesthesia was induced with propofol and vecuronium, and maintained with
      oxygen (33%), nitrous oxide and sevoflurane. Two hours after the beginning of
      operation, alternating pulse was observed suddenly on arterial pressure waves
      without marked change in hemodynamic parameters. The operation was performed
      uneventfully and alternating pulse disappeared after changing from prone position
      to supine. Using a transesophageal echocardiography, large-sized bacterial
      vegetation (22 x 17 mm) was found in the left ventricle. Second operation was
      performed to remove vegetation at three weeks after first operation. Alternating
      pulse is generally considered as a sign of severe left ventricular dysfunction
      such as dilated cardiomyopathy and aortic stenosis. Therefore, we should be
      careful about pulse disorder during operation for the patient who is in the state
      of severe heart failure.

PMID- 19108499
TI  - [Anesthetic management for laryngoscopic evaluation of upper airway stenosis
      using our modified endoscopic mask].
AB  - Young children are at increased risk for hypoxaemia and hypercapnea during
      flexible laryngoscopy due to the small size and increased collapsibility of their
      airways. To evaluate upper airway stenosis of a 5-year-old girl presenting with
      retractive inspiratory breathing, we developed a modified endoscopy mask
      consisting of a regular face mask where the original port for endoscope was
      replaced by a disposable rubber dam. This setting allows a leak-free passage of
      both nasal and oral endoscopy and enables emergent endoscopic intubation through
      a small hole of a rubber dam. Using this airtightly sealed modified mask, we
      successfully managed diagnostic endoscopy of laryngomalacia and evaluated
      infolding of arytenoids under spontaneous ventilation with 100% oxygen.

PMID- 19108500
TI  - [Patients hospitalized the day before operation are satisfied with outpatient
      preoperative evaluation system].
AB  - BACKGROUND: Recently, shortening of hospitalization has increased the number of
      hospitalization the day before operation in Japan. Appropriate preoperative
      anesthetic evaluation systems should be developed to maintain the same quality
      and efficiency of evaluation as for patients hospitalized earlier. Patient
      satisfaction is an important consideration in this program. METHODS: We adopted
      an outpatient preoperative evaluation system for patients hospitalized the day
      before operation, using an original anesthesia application form, from November
      2006. Forms containing multiple-choice questions regarding medical history and
      medications were completed by patients' doctors and submitted to us before
      evaluation. We examined the system use each month and conducted a survey using
      questionnaires on patient satisfaction in 42 patients using the system 8 months
      after its introduction. RESULTS: The proportion of patients using the system
      among surgical patients increased from 8.9% to 45.2% in half a year. The
      application form yielded detailed information efficiently and enabled sufficient
      preoperative management. In the questionnaire survey, 94.1% of the patients were
      satisfied with our new system due to early understanding and anxiety reduction,
      reduction of burden after hospitalization, and appropriate preoperative
      management. CONCLUSIONS: Our new system enabled improvement in quality and
      efficiency of perioperative management and increase in patient satisfaction in
      preoperative evaluation for hospitalization the day before operation.

PMID- 19108501
TI  - [Team training for anesthesia-related difficult airway management performed by
      participation of surgical center nurses and anesthesiologists].
AB  - BACKGROUND: Difficult airway management (DAM) is one of the most important issues
      for anesthesiologists. The DAM practical seminar was held for the purpose of
      improving skill and ability for decision-making to the anesthesiologist's DAM.
      METHODS: In clinical setting, perioperative medical team, which consists of
      anesthesiologists and nurses, has to struggle against difficult airway cases. To
      improve the ability of team practice for DAM, we started a training program
      corresponding to difficult airway management which a nurse and the
      anesthesiologist jointly perform in the Hyogo College of Medicine Hospital
      Central Operation Center. RESULTS: From September 2005 to September 2006, we held
      6 seminars and 18 anesthesiologists and 17 nurses took part in them. The comment
      after attendance shows that it was very useful. In scenario session, we trained
      case management according to the routine emergency call system of Hyogo College
      of Medicine Hospital Central Operation Center. During session, we discovered the
      defect of the manual corresponding to emergency, and its improvement.
      CONCLUSIONS: The DAM practical seminar in the hospital is useful not only for
      perioperative team practice training, but also for improving the emergency call
      system.

PMID- 19108502
TI  - [Difference in tolerance to anti-hyperalgesic effect and its molecular mechanisms
      between chronic treatment with morphine, fentanyl and oxycodone in a chronic pain
      like state].
AB  - In the present study, we demonstrated that repeated treatment with fentanyl, but
      not morphine or oxycodone, causes a rapid desensitization to its ability to block
      the hyperalgesia associated with the attenuation of mu-opioid receptor
      resensitization in mice in a chronic pain-like state. In contrast, no such effect
      was noted in beta-endorphin knockout mice under the chronic pain-like conditions.
      On the assumption that beta-endorphin might be released within the spinal cord
      under pain-like conditions, we further examined whether beta-endorphin could be
      responsible for a desensitization and resensitization of fentanyl under the
      chronic pain. In cultured cells, unlike morphine, fentanyl and oxycodone induced
      a robust mu-opioid receptor internalization and, in turn, its resensitization. In
      the presence of beta-endorphin, the internalized mu-opioid receptor induced by
      fentanyl, but not oxycodone, remained within the cytosolic component even after
      washing out. The findings suggest that beta-endorphin could attenuate the
      resensitization of mu-opioid receptors. This phenomenon may explain the high
      degree of tolerance to fentanyl that develops with hyperalgesia caused by a
      chronic pain-like state.

PMID- 19108504
TI  - [Relationship between the amygdala activity and emotion/stress responses as
      revealed by fMRI and genetic analysis].
AB  - Although modern society is full of stress, we do not yet know how socio
      psychological stress is processed in the human brain. Experimental studies
      suggested that interaction of emotion and stress vulnerability may cause
      psychiatric conditions such as depression and anxiety. Elucidating this mechanism
      is one of the important topics in neuroscience. Animal experiments have shown
      that neural interaction between the amygdala and prefrontal cortex is involved in
      emotion and aversive conditioning. In the human subjects, functional magnetic
      resonance imaging is a powerful tool to investigate emotional processing in the
      brain. In this paper, the author presents the results of several fMRI experiments
      conducted in our laboratory as well as a review of the previous literature. The
      relationship between the amygdala activity and emotion/stress responses is
      investigated by means of neuroimaging and genetic analysis of neurotransmitters.

PMID- 19108503
TI  - [Amyloid-beta 42 generating process may have a biological role in regulation of
      Notch signaling intensity].
AB  - Presenilin (PS)/gamma-secretase degrades transmembrane domains of betaAPP and
      Notch-1, generating Abeta and NICD. Some cleavages by PS/gamma-secretase have
      diversity. gamma-Cleavage of betaAPP occurs mainly at residue 40 (gamma40) and at
      residue 42 (gamma42), producing Abeta 40 and Abeta42, respectively. An increase
      in the proportion of gamma42 to gamma40 cleavage is consistently observed in many
      familial Alzheimer disease-associated PS or betaAPP mutants, but it is unclear
      whether such changes in the precision of PS/gamma-secretase have any biological
      effects. We found that S3 cleavage of Notch-1 by PS/gamma-secretase has
      diversity, resulting in the production of two types of NICD with distinct ability
      to transmit Notch signaling. We also showed that the precision of S3 cleavage and
      Notch signaling intensity can be modulated by physiological factors. Although
      some PS/gamma-secretase modulators (GSM) have been known to change the precision
      of gamma-cleavage, it is unknown whether there are any modulators which change
      the S3 cleavage precision. We found such a compound increasing Notch signaling
      intensity. Our findings suggest that i) abnormally up-or-down regulated Notch
      signaling may be corrected by modifying the S3 cleavage precision and that ii)
      effects on the S3 cleavage precision should be carefully examined in developments
      of GSM lowering Abeta42 for AD therapeutics.

PMID- 19108505
TI  - [Understanding the pathogenesis of mood affective disorders through the study of
      neural stem cell biology].
AB  - Adult neurogenesis occurs in the olfactory bulb and the dentate gyrus of the
      hippocampus. It has been shown that exposure to psychosocial stress reduces cell
      proliferation in the dentate gyrus. However, little is known about how stress
      affects the proliferation kinetics of neural stem cells (NSCs) in the adult
      brain. We utilized a forced swim model of stress in the mouse and found that
      chronic stress decreased the number of NSCs. The reduction in NSC number
      persisted for weeks after the cessation of stress, but was reversed by treatment
      with antidepressant drugs, fluoxetine and imipramine. However, these
      antidepressants exhibit no direct effects on NSCs, suggesting that the effects of
      antidepressants on NSCs are mediated by serotonin. In contrast, mood stabilizing
      drugs, which are used to treat patients with bipolar disorder, act cell
      autonomously on NSCs and enhance their self-renewal capability. Importantly, this
      enhancement is achieved at therapeutically relevant concentrations in the
      cerebrospinal fluid. The pharmacological effects are mediated by the activation
      of Notch signaling in the NSC, but not by the inhibition of GSK-3b signaling or
      inositol depletion, currently popular models to explain mood stabilizers' action.
      These data provide insights into the molecular mechanisms underlying the
      pathogenesis of mood affective disorders.

PMID- 19108506
TI  - [Dynamics and functional analysis of cytokines/proteinases with drug dependence].
AB  - Drug addiction/dependence is defined as a chronically relapsing disorder that is
      characterized by compulsive drug taking, inability to limit the intake, and
      intense drug craving. The positive reinforcing/rewarding effects of drugs of
      abuse depend mainly on the mesocorticolimbic dopamine system innervating the
      nucleus accumbens. It is widely accepted that chronic intake of drugs of abuse
      causes stable changes in the structure and function of the brain, which may be
      associated with development of drug dependence as well as the long-lived
      vulnerability to relapse. Recent evidence has demonstrated that various cytokines
      and proteinases participate to the development and relapse of drug dependence,
      which may be divided into two groups. Pro-addictive factors that act to
      potentiate the rewarding effect of drugs include bFGF, BDNF, tPA, MMP-2 and MMP
      9. Anti-addictive factors such as TNF-a and GDNF act to reduce the rewarding
      effect of drugs of abuse. These findings suggest that an imbalance between pro
      addictive and anti-addictive factors contributes to the development and relapse
      of drug dependence.

PMID- 19108507
TI  - [Occupational morbidity in enterprises and institutions of Voronezh region].
AB  - The author presents long-standing statistic data on occupational morbidity,
      structure and dynamics of occupational diseases on enterprises of various
      economic branches.

PMID- 19108508
TI  - [Nervous system disorders in workers engaged into acrylonitrile production].
AB  - The article deals with results of clinical examination covering workers of
      acrylonitrile production on Krasnoyarsk synthetic rubber plant. The authors first
      described nervous system disorders in people having variable duration of exposure
      to acrylonitrile. Severity of these disorders was connected with the poison
      concentration in workplace, with content of inclusion complex containing
      acrylonitrile and hemoglobin in RBC of the exposed individuals.

PMID- 19108509
TI  - [Compression syndrome of humeral rotators: clinical signs, diagnosis].
AB  - The article contains materials on diagnosis of shoulder soft tissue diseases. To
      diagnose compression syndrome of humeral rotators, the authors used clinical and
      diagnostic complex including ultrasound of shoulder joints. Using this diagnostic
      complex enables early diagnosis of this disease and determine severity of changes
      in tissues surrounding shoulder joints.

PMID- 19108511
TI  - [Hygienic evaluation of electromagnetic situation in personnel working in
      physiatry office].
AB  - The authors consider topics of evaluating electromagnetic factors on workplace of
      medical personnel in physical therapy office, specify adequate method to define
      occupational risk, based on data of hygienic and timing studies.

PMID- 19108510
TI  - [Diagnosis of cardiopathy through rhythmocardiography and echocardiography in
      occupational diseases].
AB  - Major death cause among occupational diseases patients is cardiovascular
      disorder. Early diagnosis is required to predict heart disorders in occupational
      risk group. Rhythmocardiography helped to define autonomous cardioneuropathy on
      background of vibration disease, pneumoconiosis, chronic occupational fluorine
      manganese intoxication--this is a pathogenetic basis for early clinical
      manifestation of CHD.

PMID- 19108512
TI  - [Comparative evaluation of cellular immunity changes in occupational bronchial
      asthma patients after phytotherapy complexes vs. conventional corticosteroid
      therapy].
AB  - The studies covered changes of phenotypic markers for peripheral immunocytes in
      occupational bronchial asthma patients under influence of phytotherapy complexes
      vs. conventional corticosteroid therapy. Phytocomplexes appeared to cause
      pathogenetically positive changes in phenotypic markers content of peripheral
      blood.

PMID- 19108513
TI  - [Gas analyzers for monitoring air of workplace].
AB  - The authors present results of theoretical and practical studies of
      chemiluminescent interactions of nitrogen oxide, arsin and phosphine with ozone,
      also of converting nitrogen dioxide and ammonium into nitrogen oxide. These
      results served as a base for creation of stationary gas analyzers meeting
      requirements of nitrogen oxides, ammonium, arsin and phosphine contents in
      workplace air.

PMID- 19108514
TI  - [Selected immunological processes in viral haemorrhagic fevers infections].
AB  - The paper reviews the known facts on the immunological response in infections
      with viral haemorrhagic fevers--dangerous pathogens for life and health of
      people. Immunological process registered in infections with viruses from
      Arenaviridae, Bunyaviridae, Filoviridae and Flaviviridae have been described.
      Moreover, the immunological response in infection with the RHD (rabbit
      haemorrhagic disease) virus from Caliciviridae family have been shown as a
      potential model for laboratory research on the duration and pathogenesis of viral
      haemorrhagic fevers.

PMID- 19108515
TI  - [Detection of anti-hantavirus antibodies in forest workers in the north-east of
      Poland].
AB  - OBJECTIVE: To estimate exposition to hantaviruses in a high-risk population
      (forest workers) in the north-east of Poland. METHODS: IgG antibodies against
      virus Puumala (PUUV) and Hantaan (HTNV) were detected by ELISA in sera of 59
      forest workers from Podlaskie and Warminsko-Mazurskie provinces (group I), as
      well as in 10 employees of Regional Forest Administration in Bialystok (group
      II). MAIN OBSERVATIONS: Anti-PUUV IgG antibodies were detected in 3 persons in
      group I and 1 in group II. Anti-HTNV IgG were present in 1 person in group I and
      2 in group II, in one case accompanying strong reactivity towards PUUV. RESULTS:
      Anti-PUUV IgG, suggestive of the history of non-diagnosed PUUV infection, were
      detected in 4 persons of 69 (5,7%). Isolated anti-HTNV IgG, which could indicate
      past infection with Saaremaa virus, antigenically related to HTNV, were present
      in 2 subjects (2,9%). CONCLUSIONS: Non-diagnosed infections with Puumala and
      Saaremaa viruses seem to occur in the high risk groups in the north-east of
      Poland, with frequency comparable to other European countries. Most infections
      are probably mild or asymptomatic.

PMID- 19108516
TI  - [Epidemiological surveillance of measles occurrence in Poland in 2006 by means of
      virological and molecular methods].
AB  - The availability of sensitive cell line for isolation of measles virus from
      clinical samples and establishment RT-PCR and molecular sequencing metods have
      allowed for rapid genetic characterization of wild-type strains of measles virus.
      This sequence information makes it possible to identify the source of wild-type
      viruses and differentiate between native and reported cases. The aim of this
      study was evaluation of virus isolation in cell culture in National Laboratory in
      Poland (Department of Virology in NIH), presentation of RT-PCR and molecular
      genotyping results performed in Regional Reference Laboratory in Berlin (Robert
      Koch Institut).

PMID- 19108517
TI  - [Dirofilariasis--Dirofilaria repens--first time described in Polish patients].
AB  - In this paper the first cases of human dirofilariasis in Poland are presented.
      The clinical manifestations were typical subcutaneous nodules with the adult worm
      (D. repens) in the center. Past medical history of the 5 patients revealed their
      trips to endemic countries, so the imported infection was considered. However 2
      of these cases were difficult to interpret. It is unclear whether the infections
      should be considered endemic or imported, because of patients' short visits
      abroad which happened long time (10 years) ago.

PMID- 19108518
TI  - [Family outbreak of trichinella infection after consumption of wild boar meat].
AB  - The article presents the small family outbreak of trichinella infection following
      consumption of grilled wild boar meat. The meat had been analyzed by traditional
      method of trichinoscopy. Polish legal regulations accept the method of
      trichinoscopy for investigation of wild boar meat; however, this method showed
      lower sensitivity and carried the risk of missed diagnosis despite the presence
      of larvae trichinellosis. Thus the method requires high temperature meat
      processing or deep meat freezing. Veterinary surgeon performing the investigation
      should always instruct the consumer that high temperature meat processing is
      necessary in cases of application of method of trichinoscopy.

PMID- 19108519
TI  - [The cases of rotaviral diarrhea from Kielce and Kielce district, hospitalized in
      Kielce Voivodeship Children Hospital in 2002-2006].
AB  - The aim of the study was an analysis of rotavirus diarrhea incidence in children
      within two age ranges: between 0-4 years and between 5-9 years. Into the analysis
      there were included children from the city of Kielce and from the Kielce
      administrative district suffering from diarrhea and admitted to the hospital, in
      the years 2002-2006. METHODS: The Slidex Rota-Kit 2 tests were performed to
      confirm the rotavirus etiology of infection. RESULTS: Throughout the 5 years
      period there were hospitalized 6980 children coming from whole Swietokrzyskie
      Province. Infection caused by rotavirus was diagnosed in 2064 (29.6%) children.
      Infection caused by Salmonella was diagnosed in 405 (5.8%) children. The etiology
      of diarrhea was not established in 4511 (64.6%) children. Into the next analysis
      there were included children only from the city of Kielce and from the Kielce
      administrative district. Infection caused by rotavirus was diagnosed in 1702.
      1368 (80.4%) of children with diagnosis of rotavirus diarrhea were in the age
      group of 0-4 years, 334 (19.6%) of children were in the age group of 5-9 years.
      The highest incidence of rotavirus infection was observed in children aged 2
      years--500 (29.4%). The prevalence of infection was not related to the sex of the
      patients. There was observed an increase in the rotavirus diarrhea prevalence
      during from autumn to spring season (Nov.- May) with peak incidence in February
      (13.6%). The prevalence of diarrhea in the urban area 54.2% was higher than in
      the rural area in both age groups.

PMID- 19108521
TI  - Review of patients with hepatosteatosis and chronic hepatitis C.
AB  - We analysed a HCV RNA positive population with varied steatosis index admitted at
      Infectious Diseases and Hepatology Department, Medical University of Wroclaw in
      terms of existing abnormalities in biochemistry parameters, anthropometric
      differences as well as the antiviral therapy outcomes.

PMID- 19108520
TI  - [Community-acquired Escherichia coli meningoencephalitis in an adult--case
      report].
AB  - The case of community-acquired meningoencephalitis induced by Escherichia coli in
      a 89-year-old man was presented. The authors paid attention to possibility of
      occurring central nervous system infections caused by this bacterium also in
      adults, in community environment and without concomitant factors favourable to
      the infection.

PMID- 19108522
TI  - [Failures of antibiotic treatment in Lyme arthritis].
AB  - Antibiotic treatment has been proven to be effective in about 90% of patients
      with Lyme arthritis in controlled studies. Overt arthritis persisting in spite of
      antibiotic therapy is rare and most likely has an autoimmune background. More
      frequently, patients with history of Lyme borreliosis present with non-specific
      articular and musculosceletal symptoms, which seem to be permanent sequelae of
      arthritis or constitute part of so called post-Lyme disease syndrome, of unclear
      pathogenesis. As persistence of active infection after proper antibiotic therapy
      is unlikely, repeated treatment seems of no benefit in most of the patients. No
      more than 2-3 attempts of antibiotic therapy should be undertaken; if symptoms
      persist, symptomatic and anti-inflammatory treatment should be introduced. Lack
      of response to antibiotics should also point to co-existing musculoskeletal
      morbidity or to improper diagnosis of Lyme borreliosis, which is frequent due to
      common occurrence of false-positive serologic tests results.

PMID- 19108523
TI  - Comparison of adverse effects following immunization with vaccine containing
      whole-cell vs. acellular pertussis components.
AB  - The article presents comparative study of the incidence of adverse effects
      following vaccinations with whole cell and acellular pertussis vaccines, based on
      data collected in obligatory routine surveillance of AEFI in the period of 2001
      2005 in Poland. Comparisons done in children less then 2-years-old show in
      general about twice as high incidence of adverse effects following the whole-cell
      than the acellular vaccine. The biggest rate of proportions (RR = 4,75) was
      observed for high pitch cry. There was no significant difference in incidence of
      the most severe reactions, including encephalopathy and nonfebrile seizures, and
      there was no significant difference in allergic reactions.

PMID- 19108524
TI  - [The relationship between MMR vaccination level and the number of new cases of
      autism in children].
AB  - The MMR vaccination coverage in Malopolskie voivodeship improved rapidly and
      finally reached a high level during last years. The number of new cases of autism
      spectrum disorders in children during that time revealed a slightly rising but
      not significant trend, while the number of childhood autism were stable.
      Ecological study showed no correlation between MMR vaccination and an increased
      risk of childhood autism and autism spectrum disorders in children.

PMID- 19108525
TI  - [Efficacy of vaccination against hepatitis A in HIV infected adults from Lodz
      region--preliminary report].
AB  - OBJECTIVE: To estimate the prevalence of anti-HAV-T in the group of HIV-positive
      adults and to assess the efficacy of vaccination against viral hepatitis A.
      MATERIAL AND METHODS: In HIV-infected outpatients anti-HAV-T was determined
      (electrochemiluminescence method). Patients susceptible to HAV infection were
      qualified for vaccination. RESULTS: In the group of 175 HIV-infected patients, 70
      persons (40%) were anti-HAV-T positive. Prevalence of anti-HAV-T was
      significantly higher in patients over 35 years of age. Anti-HAV-T were present in
      all individuals older than 50 years. So far 47 patients have completed
      vaccination. Good response (detectable anti-HAV-T 1 month after booster dose) was
      obtained in 73,0% patients. Individuals with actual CD4 count above 200 cells/ul
      responded better (81,2%) than persons with CD4 count 200 cells/ul or lower (20%).
      Nadir CD4 count above 50 cells/ul predicted better response than 50 cells/ul or
      below (78,8% and 25% respectively). One year after vaccination anti-HAV-T were
      still detectable in 21 patients (56,8%). CONCLUSIONS: 1. Most of studied HIV
      positive patients (60%) were susceptible to HAV infection and should be
      vaccinated. 2. Good response to vaccination was obtained in 73% of patients and
      it was higher in persons with actual CD4 count above 200 cells/ul and nadir CD4
      count above 50 cells/ul.

PMID- 19108526
TI  - [Mumps--effect of immunizations on epidemiological situation].
AB  - In 2004, 57% of States included mumps vaccine in their routine national
      immunization programmers. Nevertheless WHO reported then global increase of mumps
      cases--654 216 in 2004 compared to 334 064 cases in 2003. Cases registered in
      Europe accounted for 38% of general accidents. In Poland, since 2004 above 90% of
      population suffered from mumps since 19 years old. After 2006, after introduction
      second mumps vaccine dose for children at age 10 years in polish routine national
      immunization program, particularly will be exposure to risk of mumps infection
      and mumps complications unvaccinated and seronegatived aged in 1985-1995.

PMID- 19108527
TI  - [Development and dilemmas of health impact assessment].
AB  - Health impact assessment (HIA) is defined as a combination of procedures, methods
      and tools which may be used to evaluate policy, program or project in the context
      of its potential impact on the population health or the distribution of health
      determinants. This approach is used under the assumption that policy, program or
      project may have an impact on health determinants. Authors of this paper
      presented origin, history and short description of this methodology as well as
      basic steps of the decision making process in which HIA is being used. The
      difficulties and challenges faced by experts using this approach as well as
      problems related to the measurement of it's effectiveness are also described. In
      conclusion authors express the view that HIA may become the universal tool used
      at all levels of decision making and in all sectors.

PMID- 19108528
TI  - [Protective factors as determinants of subjective complaints in 15-year-old
      adolescents].
AB  - The study is based on the theory of resilience. Data obtained in Polish schools
      in 2006 on 2 287 15-year-old pupils were analyzed within HBSC (Health Behaviour
      in School-aged Children) study. The index of multiple subjective complaints was
      defined as the main outcome measure. Adolescents provided information on family
      and local area well-off, social support, quality of family relations, social self
      esteem, and school climate. Each of six factors was classified into low, average
      and high level, and then 12 dummy variables were defined with average level as
      the reference category. To identify which dummy variable had significant effect
      upon subjective complaints linear regression model controlled for age was
      estimated, as well as two gender specific models. We found that strong social
      bonds are more important for predicting adolescents subjective health than
      economic factors. However, the effect of protective factors appeared to be lower
      than had been expected.

PMID- 19108529
TI  - [Evaluation of medical service quality by hospitalized patients].
AB  - The study of patient satisfaction with health care in the time of reforming the
      health care system in Poland was undertaken in Public Health School of the
      Medical Centre for Postgraduate Education in collaboration with Mazovian Public
      Health Centre and Health Promotion and Postgraduate Department of the National
      Institute of Public Health-National Institute of Hygiene. A part of the study was
      to investigate the evaluation of quality of medical services by hospitalised
      patients. The data were obtained from randomly selected samples of 391 patients
      treated in five hospitals. The original questionnaire was elaborated in Public
      Health School of the Medical Centre for Postgraduate Education. The questionnaire
      contained the demographic information and twenty five core questions concerning
      general assessment of medical care quality in hospital, evaluation by patients
      the conditions and procedures of treatment, and patient satisfaction with care
      given them by hospital staff. Almost all or majority of hospitalised patients
      highly assessed general quality of medical care in hospital as well as conditions
      and procedures of treatment and hospital staff. Nevertheless, considerable
      percentage of them perceived the waiting for hospitalisation as long (11,2%),
      they were not asked for the acceptance on the presence of other persons in the
      time of the diagnostic procedures (49,7%), did not understand or understood not
      always the information about their health (23,2%), nothing knew about the drugs
      they used (10,4%), and were not able to define, whether they had or had not the
      confidence to physician (16,1%).

PMID- 19108530
TI  - [Evidence based medicine (EBM) in health care system and treatment of individual
      patient. Part II. EBM in treatment of individual patient].
AB  - The essentials of EBM clinical guidelines has been presented. The need of the
      epidemiological interpretation of statistical analysis was pointed out. Choosen
      guideline systems as NICE, NGC, DynaMed has been discussed, as well as existing
      organisational and legal regulations. EBM converts into atificial intelligence
      through-out application of ontology, semantic web, statistical modelling,
      decision making theory.

PMID- 19108531
TI  - [The principle of registration, evaluation and testing of disinfecting
      preparations].
AB  - Disinfectants are used to produce a state in which the number of living micro
      organisms has been reduced to a level which is appropriate to the practical
      situation. For any products which are included in the Biocidal Directive 98/8/EC,
      for which specific activity is claimed, test data has to be approved by the
      regulatory authority and a product license obtained before the product can be
      offered for sale. Disinfectants can be recorded as biocidal products or medical
      devices. Presently, it is possible to measure the activity of a product on
      defined micro-organisms in specified experimental conditions. Efficacy is the
      result of the use of a product according to a defined application. To allow
      different requirements in different areas of application, separate tests and pass
      criteria have been or will be prepared for each of following three areas of
      application: medical, veterinary and group comprising food, industrial, domestic
      and institutional areas. The laboratory methods to be used for testing the
      activity of chemical disinfectants meets the European standards. The tests are
      categorised on a modular basis as follows: phase 1 tests, phase 2 step 1 tests,
      phase 2 step 2 tests and phase 3 tests. In order to claim that a product has
      disinfectant properties, suitable for use in the medical area, the product shall
      be tested according to European standards: phase 2 step 1 tests, phase 2 step 2
      tests. Phase 1 tests are not required to support claims for chemical
      disinfectants used in human medicine. Only phase 1 tests are required to support
      claims for active substances for which no particular area of application is
      specified. Medical devices are subjects to the European Directive 93/42/EEC which
      requires that a product must carry a CE mark. Disinfectants which are intended
      specifically by its manufacturer to be used on medical devices are themselves
      medical devices and so these products, as well as conforming to the instrument
      disinfection European standards as specified in EN 14885, are also required to
      carry a CE mark.

PMID- 19108532
TI  - [Direct and indirect treatment cost of patient with ischaemic heart disease].
AB  - Authors of this paper attempted to evaluate the cost of treatment of hypothetical
      patient with ischaemic heart disease during the period 16 years. The medical
      costs (costs of medicines, diagnostic procedures, coronary angioplasty and bypass
      surgery) and indirect costs of lost productivity have been estimated.

PMID- 19108534
TI  - NIH program tackles confusing cases.

PMID- 19108533
TI  - Sorting out hoof beats.

PMID- 19108535
TI  - In defense of a dying art.

PMID- 19108537
TI  - Fleeting phobics.

PMID- 19108536
TI  - Captive markets.

PMID- 19108538
TI  - Make professionalism a priority.

PMID- 19108539
TI  - Cyber safety net.

PMID- 19108540
TI  - Inspector Lachance.

PMID- 19108541
TI  - Evolution of the zebra.

PMID- 19108542
TI  - Lepromatous leprosy masquerading as acute sarcoidosis: a case report and
      literature review.
AB  - Leprosy is uncommon in North America. Because it has a prolonged incubation
      period and can masquerade with a variety of manifestations, many patients with
      leprosy experience a significant delay in diagnosis and treatment. Lepra
      reactions are of 2 types: reversal (type 1) and erythema nodosum leprosum (ENL)
      (type 2). Type 1 or reversal reactions represent an increase in cell-mediated
      immunity, whereas type 2 or ENL is caused by antigen-antibody complex formation
      and deposition after antigen release from dying lepra bacilli. This article
      describes the diagnostic challenges presented by a Minnesota patient eventually
      found to have lepromatous leprosy. That challenge was compounded by the fact that
      the clinical scenario closely mimicked connective tissue/immune complex disease
      and by the fact that the patient presented in a location where the incidence and
      prevalence of leprosy is extremely low.

PMID- 19108543
TI  - Explaining the unexplained: identifying infectious causes of critical illness and
      death in Minnesota.
AB  - The Minnesota Department of Health began its unexplained critical illness and
      death due to possible infectious etiologies (UNEX) project in 1995. In 2006, it
      also began surveillance for all possible infectious disease-related and
      unexplained deaths investigated by medical examiners (MED-X). Surveillance for
      unexplained critical illness and death is focused on determining the etiology of
      an acute illness in a previously healthy person 50 years of age or younger whose
      illness is suggestive of an infectious disease. This article describes how the
      programs operate and how they have been able to identify the causes of a number
      of unexplained deaths in Minnesota. It also discusses the need for specimen
      collection, laboratory technologies used to identify infectious agents, and the
      importance of identifying etiologies of unexplained illnesses and deaths in order
      to prevent potential outbreaks in the greater population.

PMID- 19108544
TI  - Fatigue, exercise intolerance, and weakness: lessons on herding zebras.

PMID- 19108545
TI  - The case of the broken-hearted woman: a middle-aged female with acute coronary
      symptoms.

PMID- 19108546
TI  - The trials of the returning traveler: ciprofloxacin failure in enteric fever.

PMID- 19108547
TI  - The woman who heard music: high salicylate levels and tinnitus.

PMID- 19108548
TI  - The telltale rash: a man with pretibial erythema.

PMID- 19108549
TI  - The case of the parent in pain: a young man with abrupt-onset arthritis.

PMID- 19108550
TI  - Improved methods for modelling drinking water treatment in quantitative microbial
      risk assessment; a case study of Campylobacter reduction by filtration and
      ozonation.
AB  - Quantitative microbial risk assessment (QMRA) is increasingly applied to estimate
      drinking water safety. In QMRA the risk of infection is calculated from pathogen
      concentrations in drinking water, water consumption and dose response relations.
      Pathogen concentrations in drinking water are generally low and monitoring
      provides little information for QMRA. Therefore pathogen concentrations are
      monitored in the raw water and reduction of pathogens by treatment is modelled
      stochastically with Monte Carlo simulations. The method was tested in a case
      study with Campylobacter monitoring data of rapid sand filtration and ozonation
      processes. This study showed that the currently applied method did not predict
      the monitoring data used for validation. Consequently the risk of infection was
      over estimated by one order of magnitude. An improved method for model validation
      was developed. It combines non-parametric bootstrapping with statistical
      extrapolation to rare events. Evaluation of the treatment model was improved by
      presenting monitoring data and modelling results in CCDF graphs, which focus on
      the occurrence of rare events. Apart from calculating the yearly average risk of
      infection, the model results were presented in FN curves. This allowed for
      evaluation of both the distribution of risk and the uncertainty associated with
      the assessment.

PMID- 19108551
TI  - Inactivation of Nitrosomonas europaea and pathogenic Escherichia coli by chlorine
      and monochloramine.
AB  - The purpose of this study was to measure the chlorine and monochloramine
      inactivation kinetics of Nitrosomonas europaea at 21 degrees C in the presence
      and absence of particles. The inactivation kinetics rates were compared with
      those obtained with Escherichia coli O157:H7. The results show that, in pure
      water, the use of free chlorine produced 4 log10 of N. europaea inactivation at a
      CT value of 0.8 mg.min l(-1), whereas monochloramine yielded 4 log10 of
      inactivation at CT values of approximately 9.9-16.4mg.min l(-1). With E. coli,
      chlorine produced approximately 4 1og10 of inactivation at a CT of 0.13 mg.min l(
      1), whereas monochloramine resulted in 4 logo10 of inactivation at a CT of
      approximately 9.2 mg.min l(-1). These results suggest that N. europaea is more
      resistant to monochloramine and chlorine than E. coli. Corrosion debris, soil
      material and wastewater had no statistically significant (p < 0.05) impact on the
      inactivation of N. europaea by either chlorine or monochloramine. It seems likely
      that the CT values present in distribution systems would be sufficient to control
      suspended cells of these two organisms, especially under conditions of breakpoint
      chlorination, which could be used to control nitrification. Adequate disinfection
      should prevent the growth of these organisms in a distribution system.

PMID- 19108552
TI  - Factors determining vulnerability to diarrhoea during and after severe floods in
      Bangladesh.
AB  - This paper identifies groups vulnerable to the effect of flooding on hospital
      visits due to diarrhoea during and after a flood event in 1998 in Dhaka,
      Bangladesh. The number of observed cases of cholera and non-cholera diarrhoea per
      week was compared to expected normal numbers during the flood and post-flood
      periods, obtained as the season-specific average over the two preceding and
      subsequent years using Poisson generalised linear models. The expected number of
      diarrhoea cases was estimated in separate models for each category of potential
      modifying factors: sex, age, socio-economic status and hygiene and sanitation
      practices. During the flood, the number of cholera and non-cholera diarrhoea
      cases was almost six and two times higher than expected, respectively. In the
      post-flood period, the risk of non-cholera diarrhoea was significantly higher for
      those with lower educational level, living in a household with a nonconcrete
      roof, drinking tube-well water (vs. tap water), using a distant water source and
      unsanitary toilets. The risk for cholera was significantly higher for those
      drinking tube-well water and those using unsanitary toilets. This study confirms
      that low socio-economic groups and poor hygiene and sanitation groups were most
      vulnerable to flood-related diarrhoea.

PMID- 19108553
TI  - Outbreak of Cryptosporidium parvum among children after a school excursion to an
      adventure farm, south west England.
AB  - We present the results of an outbreak investigation on a Cryptosporidium parvum
      outbreak among 35 people, (27 students and 8 teachers), who participated in a
      school excursion to an outdoor adventure farm in South West England, from 22 to
      26 May 2006. A cohort study was implemented to investigate possible sources of
      infection during the farm visit. The most likely transmission route was contact
      with faecally contaminated surface water following heavy rainfall, or consumption
      of water from the private well. Disinfection of the water reservoir was by
      chlorination, to which cryptosporidium is resistant. Supplemental disinfection or
      filtration methods of private water supplies on livestock farms may be needed.
      This study highlights the fact that epidemiological investigations of outbreaks
      as a result of environmental exposures are complex but important to inform the
      public and health professionals of the risks posed by private water supplies and
      outdoor activities. This is particularly so after heavy rainfall, as this may
      result in an increased effluent from faecally contaminated land, causing a wide
      variety of pathogens to wash into surface water and potentially, private wells.
      This poses risks for public health.

PMID- 19108554
TI  - Community and household determinants of water quality in coastal Ghana.
AB  - Associations between water sources, socio-demographic characteristics and
      household drinking water quality are described in a representative sample of six
      coastal districts of Ghana's Central Region. Thirty-six enumeration areas (EAs)
      were randomly chosen from a representative survey of 90 EAs in rural, semi-urban
      and urban residence strata. In each EA, 24 households were randomly chosen for
      water quality sampling and socio-demographic interview. Escherichia coli per 100
      ml H2O was quantified using the IDEXX Colilert system and multi-stage regression
      models estimated cross-sectional associations between water sources, sanitation
      and socio-demographic factors. Almost three quarters, 74%, of the households have
      > 2 E. coli /100 ml H2O. Tap water has significantly lower E. coli levels
      compared with surface or rainwater and well water had the highest levels.
      Households with a water closet toilet have significantly lower E. coli compared
      with those using pit latrines or no toilets. Household size is positively
      associated, and a possessions index is negatively associated, with E. coli.
      Variations in community and household socio-demographic and behavioural factors
      are key determinants of drinking water quality. These factors should be included
      in planning health education associated with investments in water systems.

PMID- 19108555
TI  - An epidemiological study of enteric viruses in sewage with molecular
      characterization by RT-PCR and sequence analysis.
AB  - The aim of this study was to assess the presence and seasonal frequency of
      various enteric viruses in wastewater treatment. The detection of astrovirus,
      norovirus, enterovirus, hepatitis A virus (HAV) and rotavirus was carried out by
      molecular analyses in concentrated water samples collected over 18 months at the
      entrance and exit of an activated sludge sewage treatment plant. The reverse
      transcriptase-polymerase chain reaction (RT-PCR) results were confirmed by
      sequencing, and comparative phylogenetic analysis was performed on the isolated
      strains. Genomes of human astrovirus and human rotavirus were identified in 26/29
      and 11/29 samples of raw sewage, respectively, and in 12/29 and 13/29 treated
      effluent samples, respectively. Some rotavirus sequences detected in
      environmental samples were very close to those of clinical strains. Noroviruses,
      enteroviruses and HAV were not detected during the study period. This could be
      related to the small sample volume, to the sensitivity of the detection methods
      or to local epidemiological situations. Frequent detection of viral RNA, whether
      infectious or not, in the exit effluent of sewage treatment indicates wide
      dispersion of enteric viruses in the environment. Consequently, viral
      contamination resulting from the use of these treated waters is a risk that needs
      to be addressed.

PMID- 19108556
TI  - An approach for developing quantitative risk-based microbial standards for fresh
      produce.
AB  - A key objective of the Good Agricultural Practices (GAP) program is to reduce the
      potential for produce to become contaminated with microbial pathogens, such as
      through irrigation water. Without microbial standards, however, it is impractical
      to decide whether there is a need to disinfect, a need to institute watershed
      protection programs, or a need to institute post-harvest disinfection regimes. To
      develop such standards, quantitative microbial risk assessments can be performed
      using pathogen monitoring data for produce. This paper presents an approach which
      can be used towards the application of a risk assessment framework to developing
      microbial standards for fresh produce. Risks of infection are estimated using
      typical monitoring data of Salmonella detected on carrots and assuming various
      scenarios of the likelihood of an individual consuming a contaminated serving of
      carrots in a given year. Estimated annual risks of infection range from 2.20 x
      10(-5) to 2.16 x 10(-3), assuming 1% and 100% of an individual's carrot servings
      are contaminated, respectively. In addition, critical factors are identified
      which need to be incorporated in such a risk assessment approach as well as their
      impact on risk estimates to provide growers with benchmarks which may be targeted
      to reduce health risks.

PMID- 19108557
TI  - Faecal contamination of a municipal drinking water distribution system in
      association with Campylobacter jejuni infections.
AB  - After heavy rains Campylobacter jejuni together with high counts of Escherichia
      coli, other coliforms and intestinal enterococci were detected from drinking
      water of a municipal distribution system in eastern Finland in August 2004. Three
      patients with a positive C. jejuni finding, who had drunk the contaminated water,
      were identified and interviewed. The pulsed-field gel electrophoresis (PFGE)
      genotypes from the patient samples were identical to some of the genotypes
      isolated from the water of the suspected contamination source. In addition,
      repetitive DNA element analysis (rep-PCR) revealed identical patterns of E. coli
      and other coliform isolates along the distribution line. Further on-site
      technical investigations revealed that one of the two rainwater gutters on the
      roof of the water storage tower had been in an incorrect position and rainwater
      had flushed a large amount of faecal material from wild birds into the drinking
      water. The findings required close co-operation between civil authorities, and
      application of cultivation and genotyping techniques strongly suggested that the
      municipal drinking water was the source of the infections. The faecal
      contamination associated with failures in cleaning and technical management
      stress the importance of instructions for waterworks personnel to perform
      maintenance work properly.

PMID- 19108558
TI  - HACCP and water safety plans in Icelandic water supply: preliminary evaluation of
      experience.
AB  - Icelandic waterworks first began implementing hazard analysis and critical
      control points (HACCP) as a preventive approach for water safety management in
      1997. Since then implementation has been ongoing and currently about 68% of the
      Icelandic population enjoy drinking water from waterworks with a water safety
      plan based on HACCP. Preliminary evaluation of the success of HACCP
      implementation was undertaken in association with some of the waterworks that had
      implemented HACCP. The evaluation revealed that compliance with drinking water
      quality standards improved considerably following the implementation of HACCP. In
      response to their findings, waterworks implemented a large number of corrective
      actions to improve water safety. The study revealed some limitations for some,
      but not all, waterworks in relation to inadequate external and internal auditing
      and a lack of oversight by health authorities. Future studies should entail a
      more comprehensive study of the experience with the use of HACCP with the purpose
      of developing tools to promote continuing success.

PMID- 19108559
TI  - Occurrence of Cryptosporidium oocysts and Giardia cysts in Norwegian groundwater
      wells in bedrock.
AB  - The occurrence of Cryptosporidium oocysts and Giardia cysts in Norwegian
      groundwater wells in bedrock has been investigated for the first time. Wells
      close to risk areas such as farming and septic tanks were chosen. In all, 20
      water samples from 20 different waterworks were collected. The samples were
      analysed for Cryptosporidium and Giardia, using US EPA Method 1623. Turbidity was
      also measured. Water samples from 10 of the waterworks were also analysed for
      Clostridium perfringens by membrane filtration. Cryptosporidium was detected in
      the groundwater samples from 3 of the waterworks. Giardia and Clostridium
      perfringens were not detected. Too few samples were analysed to verify whether
      Giardia is indeed absent from bedrock wells, and further studies are recommended
      to give more reliable data.

PMID- 19108560
TI  - Use of the ISO 9308-1 procedure for the detection of E. coil in water utilizing
      two incubation temperatures and two confirmation procedures and comparison with
      defined substrate technology.
AB  - Disinfected and non-disinfected samples have been used to determine the accuracy
      of the ISO procedure (ISO 9308-1) for detection of E. coli in drinking water.
      Samples were analysed using the ISO procedure at both 36 and 44 degrees C and
      using the defined substrate technology method Colilert-18/Quanti-Tray (Colilert
      18). Utilizing the confirmation procedure described in ISO 9308-1, large numbers
      of false positive E. coli results were obtained using the ISO primary isolation
      procedure at 36 degrees C. However, when glucuronidase production was used as the
      confirmation procedure, the 'confirmed' count of E. coli was lowest with ISO 9308
      1 performed at 36 degrees C. When TTC medium was incubated at 36 degrees C
      confirmation using production of indole at 44 degrees C resulted in 29% more 'E.
      coli' being recovered than when confirmation was performed using production of
      glucuronidase. When 44 degrees C was used as the primary isolation temperature
      the difference between the number of 'confirmed' E. coli identified using the two
      confirmation procedures was less than 1% and was not significant. Identification
      of isolates which 'confirmed' when using production of indole at 44 degrees C as
      the test method but which failed to produce beta-D-glucuronidase, showed that the
      majority of these isolates were Klebsiella oxytoca.

PMID- 19108561
TI  - Nitrogen-nitrate exposure from drinking water and colorectal cancer risk for
      rural women in Wisconsin, USA.
AB  - One unintentional result of widespread adoption of nitrogen application to
      croplands over the past 50 years has been nitrate contamination of drinking water
      with few studies evaluating the risk of colorectal cancer. In our population
      based case-control study of 475 women age 20-74 years with colorectal cancer and
      1447 community controls living in rural Wisconsin, drinking water nitrate
      exposure were interpolated to subjects residences based on measurements which had
      been taken as part of a separate water quality survey in 1994. Individual level
      risk factor data was gathered in 1990-1992 and 1999-2001. Logistic regression
      models estimated the risk of colorectal cancer for the study period, separately
      and pooled. In the pooled analyses, an overall colorectal cancer risk was not
      observed for exposure to nitrate-nitrogen in the highest category (> or =10 ppm)
      compared to the lowest category (<0.5 ppm). However, a 2.9 fold increase risk was
      observed for proximal colon cancer cases in the highest compared to the lowest
      category. Statistically significant increased distal colon or rectal cancer risk
      was not observed. These results suggest that if an association exists with
      nitrate-nitrogen exposure from residential drinking water consumption, it may be
      limited to proximal colon cancer.

PMID- 19108562
TI  - Microbiological evaluation of fecal bacterial composition from surface water
      through aquifer sand material.
AB  - When bacterial pathogens from livestock contaminate drinking water supplies, they
      can cause different forms of gastroenteritis. The objective of this study was to
      enumerate the concentrations of fecal indicator (Escherichia coli and
      enterococci) in surface water in order to determine removal efficiency by sand
      filtration. The concentrations of different indicator bacterial species were
      determined after running tertiary treated water through two tanks containing
      aquifer material. Enterococcus faecalis primers targeting the ddl gene and
      primers for Enterococcus faecium were used to identify the two species in the
      samples. A PCR assay based on the partial sequence of the 13-D-glucoronidase gene
      (uidA) for specific detection and differentiation of E. coli populations was used
      to confirm the presence of E. coli after a biochemical test. The biochemical test
      overestimated the percentage of E. faecium in our samples, but the PCR assay with
      the ddl gene produced 100% specificity with Enterococcus faecalis. The
      biochemical test was 91.5% specific in identifying E. coli. The composition of
      indicator bacteria in Santa Ana River was dominated by intestinal microflora of
      humans and animals; filtration by aquifer sand material may reduce the transport
      of indicator bacteria from surface water to groundwater.

PMID- 19108563
TI  - Water-related diseases outbreaks reported in Italy.
AB  - Water related disease outbreak (WRDO) statistics in Italy from 1998 to 2005 have
      been discussed in this paper. The true incidence of WRDO is not reflected in the
      National Surveillance System (NSS), although this study has provided information
      on pathogens associated to different water sources, incidence in Regions and
      inadequacy of regulations. 192 outbreaks and 2546 cases of WRD were reported to
      the NSS, an average of 318 cases per year. Cases were associated to shellfish
      (58.79%), drinking water (39.94%) and agricultural products (1.25%). WRDs have
      been detected in 76% of Regions: central and southern Regions showed lower
      percentage of cases (35.4%) due to under-reporting. Most of WRD cases in the
      North were related to drinking water; WRDs in marine coastal Regions were mostly
      related to shellfish. 49% of Districts (Province) notified WRDs, including only
      101 Municipalities. Pathogenic microorganisms were identified in a few cases from
      clinical investigations. They included enteric viruses, Norwalk viruses,
      Salmonella, Shigella, Giardia and Campylobacter. There is the need to improve the
      existing NSS in relation to WRDs. An adequate WRDs Surveillance System should be
      based on connection between health and environmental authorities, priority
      pathogens and critical areas identification, response capability and contingency
      plans.

PMID- 19108564
TI  - Praise for ED patient low coverage.

PMID- 19108565
TI  - What would be the effect of legally mandated nurse-patient ratios?

PMID- 19108566
TI  - Obstacles to nurse entrepreneurship. To be your own boss, overcome these
      mindsets.

PMID- 19108567
TI  - Hyperphosphatemia in renal failure.

PMID- 19108568
TI  - Scouting for Lyme disease.

PMID- 19108569
TI  - Sharing the load. Rescuing the healer after trauma.

PMID- 19108570
TI  - Circulating autoantibodies to troponin I in Emery-Dreifuss muscular dystrophy.
AB  - The pathogenesis of dilated cardiomyopathy in Emery- Dreifuss muscular dystrophy
      (EDMD) is still unknown. Autoimmune mechanisms have recently been taken into
      account. The aim of this investigation was to determine whether the level of
      circulating antibodies to heart proteins which were previously detected,
      correlates with disease progression. Troponin I was chosen as the target. Ten
      patients with EDMD and 10 age-matched normal controls were tested. An enzyme
      linked immunoassay (ELISA) technique was used to determine the possible relation
      between the level of anti-troponin I antibodies at diagnosis and at followup.
      Autoantibodies against troponin I were detected in all EDMD patients. At
      diagnosis the level was higher in the X-linked EDMD form (X-EDMD), as compared to
      the autosomal dominant form (AD-EDMD). At follow-up the elevated level of the
      autoantibodies persisted in all the EDMD cases. However, in the AD-EDMD form, the
      level was found to be significantly rising with disease progression, in the X
      EDMD form, on the other hand, it was declining. No clear-cut relationship between
      the level of the circulating antibodies and cardiac symptomatology was present.
      Detection of anti-troponin I antibodies may provide a non-invasive marker of
      early stages of dilated cardiomyopathy in EDMD.

PMID- 19108571
TI  - Characteristics of neurons and glia in the brain of Fukuyama type congenital
      muscular dystrophy.
AB  - Fukuyama type congenital muscular dystrophy accompanies central nervous system
      and ocular lesions. Morphological findings suggest that major central nervous
      system lesions, such as cortical dysplasia, are caused by the abnormal glia
      limitans due to an impairment of astrocytes. Increase of corpora amylacea and
      neurofibrillary tangles suggests acceleration of the aging process in the
      Fukuyama type congenital muscular dystrophy brain. Glycosylation of alpha
      dystroglycan is decreased in the central nervous system of Fukuyama type
      congenital muscular dystrophy in a similar manner to the skeletal muscle, but
      dystroglycan mRNA levels appear to be increased. Glycosylated alpha-dystroglycan
      is reduced in the glia limitans formed by astrocytic endfeet. Slight accumulation
      of N(epsilon)-(carboxymethyl)lysine, an oxidative modification product, is
      observed in astrocytes of Fukuyama type congenital muscular dystrophy and in an
      astrocytoma cell line with suppressed fukutin expression. Cerebral cortical
      neurons of Fukuyama type congenital muscular dystrophy and controls react with an
      antibody for core alpha-dystroglycan but not with an antibody for glycosylated
      alpha-dystroglycan. Carboxymethyl lysine is accumulated in cortical neurons of a
      severe case of Fukuyama type congenital muscular dystrophy. Both astrocytes and
      neurons appear to be sensitive to oxidative stress when fukutin is suppressed.
      However, it is still unclear how the loss of fukutin causes astrocytic and
      neuronal dysfunction. Since the central nervous system is composed of several
      components that are closely related to each other, more investigations are needed
      for thorough understanding of the Fukuyama type congenital muscular dystrophy
      brain. Moreover, since astrocytes and epithelial cells may show different
      cellular responses to fukutin suppression, it seems important to evaluate the
      functions of fukutin in each type of cell or tissue, not only to prove the
      pathogenesis of Fukuyama type congenital muscular dystrophy, but also for
      applying appropriate therapies, especially those at molecular level.

PMID- 19108572
TI  - Myostatin inhibition by a follistatin-derived peptide ameliorates the
      pathophysiology of muscular dystrophy model mice.
AB  - Gene-targeted therapies, such as adeno-associated viral vector (AAV)-mediated
      gene therapy and cell-mediated therapy using myogenic stem cells, are hopeful
      molecular strategies for muscular dystrophy. In addition, drug therapies based on
      the pathophysiology of muscular dystrophy patients are desirable.
      Multidisciplinary approaches to drug design would offer promising therapeutic
      strategies. Myostatin, a member of the transforming growth factor-beta
      superfamily, is predominantly produced by skeletal muscle and negatively
      regulates the growth and differentiation of cells of the skeletal muscle lineage.
      Myostatin inhibition would increase the skeletal muscle mass and prevent muscle
      degeneration, regardless of the type of muscular dystrophy. Myostatin inhibitors
      include myostatin antibodies, myostatin propeptide, follistatin and follistatin
      related protein. Although follistatin possesses potent myostatin-inhibiting
      activity, it works as an efficient inhibitor of activins. Unlike myostatin,
      activins regulate the growth and differentiation of nearly all cell types,
      including cells of the gonads, pituitary gland and skeletal muscle. We have
      developed a myostatin-specific inhibitor derived from follistatin, designated FS
      I-I. Transgenic mice expressing this myostatin-inhibiting peptide under the
      control of a skeletal muscle-specific promoter showed increased skeletal muscle
      mass and strength. mdx mice were crossed with FS I-I transgenic mice and any
      improvement of the pathological signs was investigated. The resulting mdx/FS I-I
      mice exhibited increased skeletal muscle mass and reduced cell infiltration in
      muscles. Muscle strength was also recovered in mdx/FS I-I mice. Our data indicate
      that myostatin inhibition by this follistatin-derived peptide has therapeutic
      potential for muscular dystrophy.

PMID- 19108573
TI  - Caveolin-3 regulates myostatin signaling. Mini-review.
AB  - Caveolins, components of the uncoated invaginations of plasma membrane, regulate
      signal transduction and vesicular trafflicking. Loss of caveolin-3, resulting
      from dominant negative mutations of caveolin-3 causes autosomal dominant limb
      girdle muscular dystrophy (LGMD) 1C and autosomal dominant rippling muscle
      disease (AD-RMD). Myostatin, a member of the muscle-specific transforming growth
      factor (TGF)-beta superfamily, negatively regulates skeletal muscle volume.
      Herein we review caveolin-3 suppressing of activation of type I myostatin
      receptor, thereby inhibiting subsequent intracellular signaling. In addition, a
      mouse model of LGMD1C has shown atrophic myopathy with enhanced myostatin
      signaling. Myostatin inhibition ameliorates muscular phenotype in the model
      mouse, accompanied by normalized myostatin signaling. Enhanced myostatin
      signaling by caveolin-3 mutation in human may contribute to the pathogenesis of
      LGMD1C. Therefore, myostatin inhibition therapy may be a promising treatment for
      patients with LGMD1C. More recent studies concerning regulation of TGF-beta
      superfamily signaling by caveolins have provided new insights into the
      pathogenesis of several human diseases.

PMID- 19108574
TI  - Dok-7/MuSK signaling and a congenital myasthenic syndrome.
AB  - Skeletal muscle contraction is controlled by motor neurons, which contact the
      muscle at the neuromuscular junction (NMJ). The formation and maintenance of the
      NMJ, which includes the aggregation of densely packed clusters of acetylcholine
      receptor (AChR) opposite the motor nerve terminal, is orchestrated by muscle
      specific receptor tyrosine kinase, MuSK. Recently, a MuSK-interacting cytoplasmic
      adaptor-like protein Dok-7 was identified and its localization at the
      postsynaptic region of the NMJ was revealed. Mice lacking Dok-7 have a phenotype
      indistinguishable from MuSK-deficient mice, and fail to form both AChR clusters
      and NMJs. In cultured myotubes, Dok-7 is required for MuSK activation and AChR
      clustering. Thus, Dok-7 is essential for neuromuscular synaptogenesis and it
      appears that the regulatory interaction of Dok-7 with MuSK is integrally involved
      in this process. In humans there are both autoimmune and genetic causes of
      defective neuromuscular transmission that gives rise to the fatigable muscle
      weakness known as myasthenia. DOK7 has been found to be a major locus for
      mutations that underlie a genetic form of myasthenia with a characteristic 'limb
      girdle' pattern of muscle weakness (DOK7 CMS). Patients with DOK7 CMS have small,
      simplified NMJs but normal AChR function. The most common mutation causes a COOH
      terminal truncation, which greatly impairs Dok-7's ability to activate MuSK.
      Recently, a series of differing DOK7 mutations have been identified, which affect
      not only the COOH-terminal region but also the NH2-terminal moiety. The study of
      these mutations may help understand the underlying pathogenic mechanism of DOK7
      CMS.

PMID- 19108576
TI  - The facts. CARNA's approach to addictions: an open letter to UNA.

PMID- 19108575
TI  - Vasodilation of intramuscular arterioles under shear stress in dystrophin
      deficient skeletal muscle is impaired through decreased nNOS expression.
AB  - Duchenne muscular dystrophy (DMD) is a lethal X-linked disorder of striated
      muscle caused by the absence of dystrophin. Recently, impairment of vascular
      dilation under shear stress has been found in DMD, but the underlying molecular
      mechanism is not fully understood. Moreover, dilation of intramuscular
      arterioles, which may be a key to the molecular pathogenesis, has not been
      addressed yet. We examined dilation of arterioles in the mouse cremaster muscle
      under shear stress due to ligation. The vasodilation was significantly impaired
      in dystrophin-deficient mdx mice as well as in neuronal nitric oxide synthase
      (nNOS)-deficient mice; however, neither endothelial NOS-deficient mice nor alpha1
      syntrophin-deficient mice showed any difference in vasodilation from control
      mice. These results indicate that nNOS is the main supplier of nitric oxide in
      shear stress-induced vasodilation in skeletal muscle, but that the sarcolemmal
      localization of nNOS is not indispensable for the function. In contrast, the
      response to acetylcholine or sodium nitroprusside was not impaired in mdx or nNOS
      deficient mice, suggesting that pharmacological treatment using a vasoactive
      agent may ameliorate skeletal and cardiac muscle symptoms of DMD.

PMID- 19108577
TI  - Patient safety should NOT be a priority in health care! Part I: why we engage in
      at-risk behaviours.

PMID- 19108578
TI  - Two ER nurses take up Liepert's invitation to speak up.

PMID- 19108579
TI  - Nucleosome DNA bendability matrix (C. elegans).
AB  - An original signal extraction procedure is applied to database of 146 base
      nucleosome core DNA sequences from C. elegans (S. M. Johnson et al. Genome
      Research 16, 1505-1516, 2006). The positional preferences of various
      dinucleotides within the 10.4 base nucleosome DNA repeat are calculated,
      resulting in derivation of the nucleosome DNA bendability matrix of 16x10
      elements. A simplified one-line presentation of the matrix ("consensus" repeat)
      is ...A(TTTCCGGAAA)T.... All 6 chromosomes of C. elegans conform to the
      bendability pattern. The strongest affinity to their respective positions is
      displayed by dinucleotides AT and CG, separated within the repeat by 5 bases. The
      derived pattern makes a basis for sequence-directed mapping of nucleosome
      positions in the genome of C. elegans. As the first complete matrix of
      bendability available the pattern may serve for iterative calculations of the
      species-specific matrices of bendability applicable to other genomic sequences.

PMID- 19108580
TI  - Identify protein-coding genes in the genomes of Aeropyrum pernix K1 and
      Chlorobium tepidum TLS.
AB  - The problem that how many protein-coding genes there are in the genome of
      Aeropyrum pernix K1 has confused many scientists since the sequencing in 1999. In
      this paper, the protein-coding genes in A. pernix K1 are identified from the
      original and current NITE annotation by using the Aper_ORFs method. Consequently,
      702 of 704 experimentally validated genes are correctly predicted as coding,
      which means the sensitivity of the method is 702/704 approximately 99.7%. This
      sensitivity is one percent higher than that of the versatile bacterial gene
      finding program, ZCURVE 1.0. The number of genes determined in this work is 1699.
      This number is very closely equal to that of the current NITE annotation, which
      is 1700. Therefore, the two independent predictions may end the ten-years-lasting
      controversy about gene number in this genome. Furthermore, the Aper_ORFs method
      is extended to identify protein-coding genes in the genome of Chlorobium tepidum
      TLS and about 98% of the function-known genes are correctly predicted as coding.
      In addition, 188 hypothetical ORFs are identified as non-coding in the genome.
      Mapping point analysis shows that these ORFs have different base frequency
      distribution with that of function-known genes, suggesting that most of them do
      not encode proteins. It's hoped the Aper_ORFs method will become a useful tool
      for gene annotation in newly sequenced bacterial and archaeal genomes, as long as
      the G+C content of which is similar with that of A. pernix.

PMID- 19108581
TI  - Alprazolam intercalates into DNA.
AB  - In vitro interaction of a benzodiazepine group of drugs Alprazolam (Alp), a
      hypnotic and tranquilizer, with DNA was studied by various methods. Absorption
      spectrophotometric study showed that Alp binds strongly with supercoiled pUC 19
      DNA and the calculated binding constant is 8.245x10(3) M(-1) in 10 mM Tris-Cl
      buffer, pH 7.4. Spectrofluorometric study showed that ethidium bromide induced
      DNA fluorescence intensity was reduced completely after addition of Alp. But Alp
      did not interfere with the interaction of Hoechst 33258, a DNA minor groove
      binder, with plasmid DNA. Circular dichroic spectroscopic study showed that with
      the gradual increase in Alp concentrations, both the positive and the negative
      peaks of DNA were gradually decreased and at higher concentrations of Alp (60
      microM and 80 microM), the negative peaks became positive indicating the
      intercalation and the conformational change in the DNA. Binding of Alp with DNA
      increased the thermal stability of DNA by 6 degrees C with respect to the mock
      treated sample. Gel electrophoresis study of supercoiled pUC 19 DNA showed more
      compact structure as a result of Alp binding. Transmission electron microscopic
      observations also confirmed this compactness. Thus, our observations suggest the
      strong interaction of Alp with DNA, which may raise serious questions about the
      random uses of Alprazolam.

PMID- 19108582
TI  - Computational study of the sulfonylated amino acid hydroxamates binding to the
      zinc ion within the active site of carbonic anhydrase.
AB  - The B3LYP/6-311+G(d,p) method and three ONIOM extrapolation methods ONIOM
      (B3LYP/6-311+G(d,p): AM1); ONIOM(B3LYP/6-311+G(d,p): MNDO); ONIOM (B3LYP/6
      311+G(d,p): HF/3-21G(d)) were used to characterize the complexes of Zn2+ cation
      with anionic sulfonylated amino acid hydroxamates (RSO2NH-AA-CON(-)OH),
      possessing an unsubstituted RSO2NH-amino acyl moiety. According to the R moiety
      we distinguish between pentafluorophenyl and 4-methoxyphenyl derivates. The amino
      acid hydroxamates included in the study were the Gly, Ala, and Leu derivates. Of
      the inhibitors investigated, the weakest zinc affinity exhibits the
      pentafluorophenyl derivate with Gly amino acid and the strongest affinity the 4
      methoxyphenyl derivate with Leu amino acid. The inhibitors form bidentate
      coordination bonds with the zinc cation by means of the sulfonyl oxygen and the
      ionized hydroxamate nitrogen atoms, respectively. The zinc affinities computed
      using the B3LYP/6-311 +G(d,p)// HF/6-31 +G(d,p) method are in very good agreement
      with the full density functional theory (DFT) B3LYP/6-311+G(d,p)//B3LYP/6
      311+G(d,p) method and this method can be adopted to model larger complexes of
      inhibitors with the active site of carbonic anhydrase.

PMID- 19108583
TI  - Immunophilins and HIV-1 V3 loop for structure-based anti-AIDS drug design.
AB  - The model of the structural complex of cyclophilin A (CycA) belonging to the
      immunophilins family with the HIV-MN gp120 V3 loop was generated, and the
      computer-aided design of the immunophilin-derived peptide able to mask the
      biologically crucial V3 segments was implemented. To this end, the following
      problems were solved: (i) the NMR-based conformational analysis of the HIV-MN V3
      loop was put into effect, and its low energy structure fitting the input
      experimental observations was determined; (ii) molecular docking of this V3
      structure with the X-ray conformation of CycA was carried out, and the energy
      refining the simulated structural complex was performed; (iii) the matrix of
      inter-atomic distances for the amino acids of the molecules forming part of the
      built over-molecular ensemble was computed, the types of interactions responsible
      for its stabilization were analyzed, and the CycA stretch, which accounts for the
      binding to V3, was identified; (iv) the most probable 3D structure for this
      stretch in the unbound state was predicted, and its collation with the X-ray
      structure for the corresponding site of CycA was performed; (v) the potential
      energy function and its constituents were studied for the structural complex
      generated by molecular docking of the V3 loop with the CycA peptide offering the
      virtual molecule that imitates the CycA segment, making a key contribution to the
      interactions of the native protein with the HIV-1 principal neutralizing
      determinant; (vi) as a result of the studies above, the designed molecule was
      shown to be capable of the efficacious blockading the functionally crucial V3
      sites; and (vii) based on the joint analysis of the evidence obtained previously
      and in the present study, the composition of the peptide cocktail presenting the
      promising anti-AIDS pharmacological substance was developed. The molecules
      simulated here by molecular modeling methods may become the first representatives
      of a new class of the chemical compounds (immunophilin-derived peptides) offering
      the looking-forward basic structures for the design of efficacious and safe
      antiviral agents.

PMID- 19108584
TI  - Homology modeling of GLUT4, an insulin regulated facilitated glucose transporter
      and docking studies with ATP and its inhibitors.
AB  - GLUT4 is a 12 transmembrane (TM) protein belonging to the Class I facilitated
      glucose transporter family that transports glucose into the cells in an insulin
      regulated manner. GLUT4 plays a key role in the maintenance of blood glucose
      homeostasis and inhibition of glucose transporter activity may lead to insulin
      resistance, hallmark of type 2 diabetes. No crystal structure data is available
      for any members of the facilitated glucose transporter family. Here, in this
      paper, we have generated a homology model of GLUT4 based on experimental data
      available on GLUT1, a Class I facilitated glucose transporter and the crystal
      structure data obtained from the Glycerol 3-phosphate transporter. The model
      identified regions in GLUT4 that form a channel for the transport of glucose
      along with the substrate interacting residues. Docking and electrostatic
      potential data analysis of GLUT4 model has mapped an ATP binding region close to
      the binding site of cytochalasin B and genistein, two GLUT4 inhibitors, and this
      may explain the mechanism by which these inhibitors could potentially affect the
      GLUT4 function.

PMID- 19108585
TI  - The membrane proximal extracellular domain of human hGC-B folds independently.
AB  - Human Guanylyl Cyclase B (hGC-B) is a single-transmembrane receptor protein which
      upon binding C-type natriuretic peptide (CNP) to its extracellular domain
      catalyzes the intracellular conversion of GTP to the second messenger cGMP. cGMP
      in turn affects various physiological processes such as smooth muscle
      contraction, cell proliferation, phototransduction, and salt as well as fluid
      homeostasis. The 3-dimensional binding site of the peptide hormone is unknown,
      and the binding mechanism is not yet understood. Therefore, a model of the C
      terminal moiety of the extracellular domain of human GC-B containing the
      potential binding site was derived from the crystal structure of (GC-A). The
      selected protein sequence was provided with an N-terminal TEV-cleavage site and
      fused with a 109 aa thioredoxin-tag and a hexahistidine-tag. The identity of the
      purified 25 kDa protein was confirmed by protein mass fingerprint and its
      secondary structure was determined by CD- and NMR-spectroscopy. The protein
      proved to be properly folded with the observed secondary structure matching the
      predicted secondary structure and the homologous structure in the extracellular
      domain of GC-A. Size exclusion chromatography confirmed the monomeric state of P
      hGC-B.

PMID- 19108586
TI  - Molecular modeling studies of the interaction between Plasmodium falciparum HslU
      and HslV subunits.
AB  - The PfHslUV, a Plasmodium falciparum homolog of prokaryotic HslUV systems, is a
      newly identified drug target. The HslUV complex is an assembly of Heat Shock
      Locus gene products U and V. The formation of complete complex is essential for
      the proteasome to carry out its biochemical and physiological role in the
      parasite, namely to degrade specific target proteins in an ATP-dependent
      chaperone assisted manner. PfHslV subunit, a protease, exhibits increased
      proteolytic activity in the presence of PfHslU, the subunit believed to be
      responsible for allosteric activation of PfHslV. In the present work, we have
      employed computational methods to simulate the interaction of PfHslU and PfHslV
      subunits. We have used three methods--namely homology modeling, molecular docking
      and computational alanine scanning to model the complex, to predict the binding
      mode of PfHslU-V interaction and to predict the binding-energy hot-spots in
      protein-protein interface, respectively. The three dimensional models of PfHslV
      and PfHslU have been generated using MODELLER, based on the crystal structures of
      prokaryotic HslUV complex as templates. The modeled structures were docked using
      PatchDock, a geometry-based molecular docking algorithm. Finally, a three
      dimensional PfHslUV complex model was generated that helped in comparing protein
      protein interface characteristics with that of crystal structures of prokaryotic
      HslUV. Further, computational alanine scanning analysis of the generated complex
      was performed to calculate the binding free energy changes (DeltaDeltaGbind),
      which helped in identifying residues crucial for PfHslU and PfHslV interactions.

PMID- 19108587
TI  - Molecular dynamics simulations to investigate the aggregation behaviors of the
      Abeta(17-42) oligomers.
AB  - The amyloid beta-peptides (Abetas) are the main protein components of amyloid
      deposits in Alzheimer's disease (AD). Detailed knowledge of the structure and
      assembly dynamics of Abeta is important for the development of properly targeted
      AD therapeutics. So far, the process of the monomeric Abeta assembling into
      oligomeric fibrils and the mechanism underlying the aggregation process remain
      unclear. In this study, several molecular dynamics simulations were conducted to
      investigate the aggregation behaviors of the Abeta(17-42) oligomers associated
      with various numbers of monomers (dimer, trimer, tetramer, and pentamer). Our
      results showed that the structural stability of the Abeta(17-42) oligomers
      increases with increasing the number of monomer. We further demonstrated that the
      native hydrophobic contacts are positive correlated with the beta-sheet contents,
      indicating that hydrophobic interaction plays an important role in maintaining
      the structural stability of the Abeta(17-42) oligomers, particularly for those
      associated with more monomers. Our results also showed that the stability of the
      C-terminal hydrophobic segment 2 (residues 30-42) is higher than that of the N
      terminal hydrophobic segment 1 (residues 17-21), suggesting that hydrophobic
      segment 2 may act as the nucleation site for aggregation. We further identified
      that Met35 residue initiates the hydrophobic interactions and that the
      intermolecular contact pairs, Gly33-Gly33 and Gly37-Gly37, form a stable
      "molecular notch", which may mediate the packing of the beta-sheet involving many
      other hydrophobic residues during the early stage of amyloid-like fibril
      formation.

PMID- 19108588
TI  - Disruption mechanism in the helix of SPF peptide by interchanging E5 and K10
      residues: inference from molecular dynamics study.
AB  - Seminalplasmin (SPLN) is a 47-residue peptide
      (SDEKASPDKHHRFSLSRYAKLANRLANPKLLETFLSKWIGDRGNRSV) from bovine seminal plasma. It
      has broad spectrum antimicrobial activity, without any hemolytic activity. The 28
      40 segment of SPLN with the sequence PKLLETFLSKWIG, designated as SPF, is the
      most hydrophobic stretch of SPLN and primarily responsible for the membrane
      perturbing activity of SPLN. It was reported that SPF has a helical structure and
      the interchange of E5 and K10 residues disrupted the helical structure. The
      present paper reports a possible mechanism of disruption of the helical structure
      of SPF peptide during the interchange of E5 and K10 residues. The result is based
      on simulated annealing and molecular dynamics simulation studies on SPF and its
      four analogues with K10E, K10D, E5K, and E5K & K10E substitutions. It showed that
      K10 residue has a critical role in maintaining the highest helical content and
      the positions of charged residues are also very important for maintaining the
      helical structure of the SPF peptide. Formation of some new long-range hydrogen
      bonds and the rupture of some short-range hydrogen bonds involving the tenth
      residue led to the disruption of helical structure of SPF peptide when E5 and K10
      residues are interchanged.

PMID- 19108589
TI  - Conserved water mediated H-bonding dynamics of inhibitor, cofactor, Asp 364 and
      Asn 303 in human IMPDH II.
AB  - The IMPDH (Inosine monophosphate dehydrogenase)-II is largely produced in cancer
      cells. Extensive MD-simulation (2 ns) of the 1B3O, 1NFB, 1NF7, 1LRT, and 1MEW PDB
      structures revealed the presence of a conserved water molecule, which is H-bonded
      and stabilized by the surrounding ribose hydroxyl (O2) of inhibitor, nitrogen
      (NN) of cofactor, carboxyl oxygen (OD2) and amide nitrogen atoms of the active
      site Asp 364 and Asn 303 of human. These water-mediated interaction are partially
      supported in the solvated and X-ray structures. The stereochemistry of the four-
      centered H-bonds around the conserved water center may be exploited to design a
      better model inhibitor for IMPDH-II.

PMID- 19108590
TI  - Inactivation kinetics of beta-N-acetyl-D-glucosaminidase from green crab (Scylla
      serrata) in dioxane solution.
AB  - Beta-N-acetyl-D-glucosaminidase (NAGase, EC.3.2.1.52), which catalyzes the
      cleavage of N-acetylglucosamine polymers, is a composition of chitinase and
      cooperates with endo-chitinase and exo-chitinase to disintegrate chitin into N
      acetylglucosamine (NAG). In this investigation, A NAGase from green crab (Scylla
      serrata) was purified and the effects of dioxane on the enzyme activity for the
      hydrolysis of p-Nitrophenyl-N-acetyl-beta-D-glucosaminide (pNP-NAG) were studied.
      The results show that appropriate concentrations of dioxane can lead to
      reversible inactivation of the enzyme and the inactivation is classified as mixed
      type. The value of IC50, the dioxane (inactivator) concentration leading to 50%
      activity lost, is estimated to be 0.68%. The kinetics of inactivation of NAGase
      in the appropriate concentrations of dioxane solution has been studied using the
      kinetic method of the substrate reaction. The rate constants of inactivation have
      been determined. The results showed that k+0 is much larger than k'+0, indicating
      the free enzyme molecule is more fragile than the enzyme-substrate complex in the
      dioxane solution. It is suggested that the presence of the substrate offers
      marked protection of this enzyme against inactivation by dioxane.

PMID- 19108591
TI  - DNA denaturation under freezing in alkaline medium.
AB  - It is generally accepted that DNA conserves its secondary structure after a
      freeze-thaw cycle. A negligible amount of degradation occurs after this
      procedure. Degradation becomes appreciable only after multiple cycles of freezing
      and thawing. In this study, we have found that a single freeze-thaw cycle in
      alkaline medium (pH>or=10.8) gives rise to denaturation of calf thymus DNA,
      although the melting temperature of intact DNA in the solution used for the
      freeze-thaw experiments is higher than 60 degrees C. The degree of denaturation
      is almost independent of the regime of freezing. The melting curve obtained after
      DNA is frozen at -2 degrees C and then thawed is almost the same as after a
      freezing carried out in liquid nitrogen (-196 degrees C). However, incubation in
      the same solution at 0 degrees C for 24 hours without freezing does not give rise
      to any denaturation. The degree of denaturation caused by freezing increases with
      pH (if pH>or=10.8) and decreases with Na2CO3 concentration at fixed pH and [Na+],
      although Na2CO3 decreases the melting temperature of intact DNA. A preliminary
      treatment of DNA with cisplatin or transplatin (0.01 Pt atoms per nucleotide)
      gives rise to a full recovery of the DNA secondary structure after freezing and
      thawing similar to what occurs after heating DNA to 100 degrees C and quick
      cooling. Possible mechanisms that may cause DNA denaturation during a freeze-thaw
      cycle in alkaline medium are discussed.

PMID- 19108592
TI  - Reproductive health of bass in the Potomac, U.S.A., drainage: part 2. Seasonal
      occurrence of persistent and emerging organic contaminants.
AB  - The seasonal occurrence of organic contaminants, many of which are potential
      endocrine disruptors, entering the Potomac River, USA, watershed was investigated
      using a two-pronged approach during the fall of 2005 and spring of 2006. Passive
      samplers (semipermeable membrane device and polar organic chemical integrative
      sampler [POCIS]) were deployed in tandem at sites above and below wastewater
      treatment plant discharges within the watershed. Analysis of the samplers
      resulted in detection of 84 of 138 targeted chemicals. The agricultural
      pesticides atrazine and metolachlor had the greatest seasonal changes in water
      concentrations, with a 3.1- to 91-fold increase in the spring compared with the
      level in the previous fall. Coinciding with the elevated concentrations of
      atrazine in the spring were increasing concentrations of the atrazine degradation
      products desethylatrazine and desisopropylatrazine in the fall following spring
      and summer application of the parent compound. Other targeted chemicals
      (organochlorine pesticides, polycyclic aromatic hydrocarbons, and organic
      wastewater chemicals) did not indicate seasonal changes in occurrence or
      concentration; however, the overall concentrations and number of chemicals
      present were greater at the sites downstream of wastewater treatment plant
      discharges. Several fragrances and flame retardants were identified in these
      downstream sites, which are characteristic of wastewater effluent and human
      activities. The bioluminescent yeast estrogen screen in vitro assay of the POCIS
      extracts indicated the presence of chemicals that were capable of producing an
      estrogenic response at all sampling sites.

PMID- 19108593
TI  - Is your preanesthetic medical history form state-of-the-art?

PMID- 19108595
TI  - Retrospective outcomes evaluation of 100 parenteral moderate and deep sedations
      conducted in a general practice dental residency.
AB  - An abstract of this study was presented at the American Association for Dental
      Research (AADR) Dental Anesthesiology Research Group in Honolulu, Hawaii, in
      March of 2004. This study was conducted to correlate the intraoperative and
      postoperative morbidity associated with moderate and deep sedation, also known as
      monitored anesthesia care (MAC), provided in a General Practice Residency (GPR)
      clinic under the supervision of a dentist anesthesiologist. After internal review
      board approval was obtained, 100 parenteral moderate and deep sedation cases
      performed by the same dentist anesthesiologist in collaboration with second year
      GPR residents were randomly selected and reviewed by 2 independent evaluators.
      Eleven morbidity criteria were assessed and were correlated with patient age,
      gender, American Society of Anesthesiology Physical Status Classification
      (ASAPS), duration of procedure, and anesthetic protocol. A total of 39 males and
      61 females were evaluated. Patients' ASAPS were classified as I, II, and III,
      with the average ASAPS of 1.61 and the standard deviation (STDEV) of 0.584. No
      ASPS IV or V was noted. Average patient age was 33.8 years (STDEV, 14.57), and
      the average duration of procedure was 97.5 minutes (STDEV, 42.39). Three
      incidents of postoperative nausea and vomiting were reported. All 3 incidents
      involved the ketamine-midazolam-propofol anesthetic combination. All patients
      were treated and were well controlled with ondansetron. One incident of tongue
      biting in an autistic child was regarded as an effect of local anesthesia. One
      patient demonstrated intermittent premature atrial contractions (PACs)
      intraoperatively but was stable. Moderate and deep sedation, also known as MAC,
      is safe and beneficial in an outpatient GPR setting with proper personnel and
      monitoring. This study did not demonstrate a correlation between length of
      procedure and morbidity. Ketamine was associated with all reported nausea and
      vomiting incidents because propofol and midazolam are rarely associated with such
      events.

PMID- 19108594
TI  - Italian version of Corah's Dental Anxiety Scale: normative data in patients
      undergoing oral surgery and relationship with the ASA physical status
      classification.
AB  - To test the Italian translation of Corah's Dental Anxiety Scale (DAS) and to
      check the relationship between dental anxiety and the American Society of
      Anesthesiologists (ASA) physical status classification (ASA-PS), the DAS was
      translated into Italian and administered to 1072 Italian patients (620 male and
      452 female patients, ages 14-85 years) undergoing oral surgery. Patients'
      conditions were checked and rated according to the ASA-PS. The DAS ranged from 4
      to 20 (modus=8, median=10); 59.5% of patients had a DAS of 7-12, 26.1% had a
      DAS>2, and 10.3% had a DAS>15. The mean DAS was 10.29 (95% confidence
      limit=0.19); female patients were more anxious than male patients (P< .001),
      while patients older than 60 years showed a significant decrease in the level of
      anxiety. Five hundred two patients were rated as ASA-PS class P1, 502 as ASA-PS
      class P2, and 68 as ASA-PS class P3, with a mean DAS score of 9.69, 10.78, and
      11.09, respectively: the DAS difference between groups was significant (P< .001).

PMID- 19108596
TI  - Perioperative management of obstructive sleep apnea with nasal continuous
      positive airway pressure.
AB  - The high risks associated with general anesthesia in obstructive sleep apnea
      syndrome (OSAS) patients have been reported. Many authors have suggested that the
      intraoperative administration of opioids and sedatives should be limited or
      avoided because these drugs selectively impair muscle activity in the upper
      airway. We report the case of an OSAS patient who was managed with nasal
      continuous positive airway pressure (NCPAP) and treated safely in spite of the
      use of conventional anesthetic and analgesic agents typically used for patients
      without OSAS. She had little pain during the perioperative period. It is
      suggested that NCPAP is an effective treatment for not only preventing airway
      obstructive apnea but for allowing the administration of anesthetic and analgesic
      drugs without major complications.

PMID- 19108597
TI  - Nitrous oxide and the inhalation anesthetics.
AB  - Nitrous oxide is the most commonly used inhalation anesthetic in dentistry and is
      commonly used in emergency centers and ambulatory surgery centers as well. When
      used alone, it is incapable of producing general anesthesia reliably, but it may
      be combined with other inhalation and/or intravenous agents in deep
      sedative/general anesthetic techniques. However, as a single agent, it has
      impressive safety and is excellent for providing minimal and moderate sedation
      for apprehensive dental patients. To gain a full appreciation of the
      pharmacology, physiologic influences, and proper use of nitrous oxide, one must
      compare it with other inhalation anesthetics. The purpose of this CE article is
      to provide an overview of inhalation anesthetics in general and to address
      nitrous oxide more specifically in comparison.

PMID- 19108600
TI  - "A good personal scientific relationship": Philip Morris scientists and the
      Chulabhorn Research Institute, Bangkok.
AB  - BACKGROUND: This paper examines the efforts of consultants affiliated with Philip
      Morris (PM), the world's leading transnational tobacco corporation, to influence
      scientific research and training in Thailand via the Chulabhorn Research
      Institute (CRI). A leading Southeast Asian institute for environmental health
      science, the CRI is headed by Professor Dr. Her Royal Highness Princess
      Chulabhorn, the daughter of the King of Thailand, and it has assumed
      international significance via its designation as a World Health Organization
      (WHO) Collaborating Centre in December 2005. METHODS AND FINDINGS: This paper
      analyses previously confidential tobacco industry documents that were made
      publicly available following litigation in the United States. PM documents reveal
      that ostensibly independent overseas scientists, now identified as industry
      consultants, were able to gain access to the Thai scientific community. Most
      significantly, PM scientist Roger Walk has established close connections with the
      CRI. Documents indicate that Walk was able to use such links to influence the
      study and teaching of environmental toxicology in the institute and to develop
      relations with key officials and local scientists so as to advance the interests
      of PM within Thailand and across Asia. While sensitivities surrounding royal
      patronage of the CRI make public criticism extremely difficult, indications of
      ongoing involvement by tobacco industry consultants suggest the need for detailed
      scrutiny of such relationships. CONCLUSIONS: The establishment of close links
      with the CRI advances industry strategies to influence scientific research and
      debate around tobacco and health, particularly regarding secondhand smoke, to
      link with academic institutions, and to build relationships with national elites.
      Such strategies assume particular significance in the national and regional
      contexts presented here amid the globalisation of the tobacco pandemic. From an
      international perspective, particular concern is raised by the CRI's recently
      awarded status as a WHO Collaborating Centre. Since the network of WHO
      Collaborating Centres rests on the principle of "using national institutions for
      international purposes," the documents presented below suggest that more rigorous
      safeguards are required to ensure that such use advances public health goals
      rather than the objectives of transnational corporations.

PMID- 19108601
TI  - Access to essential maternal health interventions and human rights violations
      among vulnerable communities in eastern Burma.
AB  - BACKGROUND: Health indicators are poor and human rights violations are widespread
      in eastern Burma. Reproductive and maternal health indicators have not been
      measured in this setting but are necessary as part of an evaluation of a multi
      ethnic pilot project exploring strategies to increase access to essential
      maternal health interventions. The goal of this study is to estimate coverage of
      maternal health services prior to this project and associations between exposure
      to human rights violations and access to such services. METHODS AND FINDINGS:
      Selected communities in the Shan, Mon, Karen, and Karenni regions of eastern
      Burma that were accessible to community-based organizations operating from
      Thailand were surveyed to estimate coverage of reproductive, maternal, and family
      planning services, and to assess exposure to household-level human rights
      violations within the pilot-project target population. Two-stage cluster sampling
      surveys among ever-married women of reproductive age (15-45 y) documented access
      to essential antenatal care interventions, skilled attendance at birth, postnatal
      care, and family planning services. Mid-upper arm circumference, hemoglobin by
      color scale, and Plasmodium falciparum parasitemia by rapid diagnostic dipstick
      were measured. Exposure to human rights violations in the prior 12 mo was
      recorded. Between September 2006 and January 2007, 2,914 surveys were conducted.
      Eighty-eight percent of women reported a home delivery for their last pregnancy
      (within previous 5 y). Skilled attendance at birth (5.1%), any (39.3%) or > or =
      4 (16.7%) antenatal visits, use of an insecticide-treated bed net (21.6%), and
      receipt of iron supplements (11.8%) were low. At the time of the survey, more
      than 60% of women had hemoglobin level estimates < or = 11.0 g/dl and 7.2% were
      Pf positive. Unmet need for contraceptives exceeded 60%. Violations of rights
      were widely reported: 32.1% of Karenni households reported forced labor and 10%
      of Karen households had been forced to move. Among Karen households, odds of
      anemia were 1.51 (95% confidence interval [CI] 0.95-2.40) times higher among
      women reporting forced displacement, and 7.47 (95% CI 2.21-25.3) higher among
      those exposed to food security violations. The odds of receiving no antenatal
      care services were 5.94 (95% CI 2.23-15.8) times higher among those forcibly
      displaced. CONCLUSIONS: Coverage of basic maternal health interventions is
      woefully inadequate in these selected populations and substantially lower than
      even the national estimates for Burma, among the lowest in the region.
      Considerable political, financial, and human resources are necessary to improve
      access to maternal health care in these communities.

PMID- 19108602
TI  - Accessing maternal health services in eastern Burma.

PMID- 19108603
TI  - "Efforts to Reprioritise the Agenda" in China: British American Tobacco's Efforts
      to Influence Public Policy on Secondhand Smoke in China.
AB  - BACKGROUND: Each year, 540 million Chinese are exposed to secondhand smoke (SHS),
      resulting in more than 100,000 deaths. Smoke-free policies have been demonstrated
      to decrease overall cigarette consumption, encourage smokers to quit, and protect
      the health of nonsmokers. However, restrictions on smoking in China remain
      limited and ineffective. Internal tobacco industry documents show that
      transnational tobacco companies (TTCs) have pursued a multifaceted strategy for
      undermining the adoption of restrictions on smoking in many countries. METHODS
      AND FINDINGS: To understand company activities in China related to SHS, we
      analyzed British American Tobacco's (BAT's) internal corporate documents produced
      in response to litigation against the major cigarette manufacturers to understand
      company activities in China related to SHS. BAT has carried out an extensive
      strategy to undermine the health policy agenda on SHS in China by attempting to
      divert public attention from SHS issues towards liver disease prevention, pushing
      the so-called "resocialisation of smoking" accommodation principles, and
      providing "training" for industry, public officials, and the media based on BAT's
      corporate agenda that SHS is an insignificant contributor to the larger issue of
      air pollution. CONCLUSIONS: The public health community in China should be aware
      of the tactics previously used by TTCs, including efforts by the tobacco industry
      to co-opt prominent Chinese benevolent organizations, when seeking to enact
      stronger restrictions on smoking in public places.

PMID- 19108604
TI  - Identifying neural drivers with functional MRI: an electrophysiological
      validation.
AB  - Whether functional magnetic resonance imaging (fMRI) allows the identification of
      neural drivers remains an open question of particular importance to refine
      physiological and neuropsychological models of the brain, and/or to understand
      neurophysiopathology. Here, in a rat model of absence epilepsy showing
      spontaneous spike-and-wave discharges originating from the first somatosensory
      cortex (S1BF), we performed simultaneous electroencephalographic (EEG) and fMRI
      measurements, and subsequent intracerebral EEG (iEEG) recordings in regions
      strongly activated in fMRI (S1BF, thalamus, and striatum). fMRI connectivity was
      determined from fMRI time series directly and from hidden state variables using a
      measure of Granger causality and Dynamic Causal Modelling that relates synaptic
      activity to fMRI. fMRI connectivity was compared to directed functional coupling
      estimated from iEEG using asymmetry in generalised synchronisation metrics. The
      neural driver of spike-and-wave discharges was estimated in S1BF from iEEG, and
      from fMRI only when hemodynamic effects were explicitly removed. Functional
      connectivity analysis applied directly on fMRI signals failed because
      hemodynamics varied between regions, rendering temporal precedence irrelevant.
      This paper provides the first experimental substantiation of the theoretical
      possibility to improve interregional coupling estimation from hidden neural
      states of fMRI. As such, it has important implications for future studies on
      brain connectivity using functional neuroimaging.

PMID- 19108605
TI  - Activator control of nucleosome occupancy in activation and repression of
      transcription.
AB  - The relationship between chromatin structure and gene expression is a subject of
      intense study. The universal transcriptional activator Gal4 removes promoter
      nucleosomes as it triggers transcription, but how it does so has remained
      obscure. The reverse process, repression of transcription, has often been
      correlated with the presence of nucleosomes. But it is not known whether
      nucleosomes are required for that effect. A new quantitative assay describes, for
      any given location, the fraction of DNA molecules in the population that bears a
      nucleosome at any given instant. This allows us to follow the time courses of
      nucleosome removal and reformation, in wild-type and mutant cells, upon
      activation (by galactose) and repression (by glucose) of the GAL genes of yeast.
      We show that upon being freed of its inhibitor Gal80 by the action of galactose,
      Gal4 quickly recruits SWI/SNF to the genes, and that nucleosome "remodeler"
      rapidly removes promoter nucleosomes. In the absence of SWI/SNF, Gal4's action
      also results in nucleosome removal and the activation of transcription, but both
      processes are significantly delayed. Addition of glucose to cells growing in
      galactose represses transcription. But if galactose remains present, Gal4
      continues to work, recruiting SWI/SNF and maintaining the promoter nucleosome
      free despite it being repressed. This requirement for galactose is obviated in a
      mutant in which Gal4 works constitutively. These results show how an activator's
      recruiting function can control chromatin structure both during gene activation
      and repression. Thus, both under activating and repressing conditions, the
      activator can recruit an enzymatic machine that removes promoter nucleosomes. Our
      results show that whereas promoter nucleosome removal invariably accompanies
      activation, reformation of nucleosomes is not required for repression. The
      finding that there are two routes to nucleosome removal and activation of
      transcription-one that requires the action of SWI/SNF recruited by the activator,
      and a slower one that does not-clarifies our understanding of the early events of
      gene activation, and in particular corrects earlier reports that SWI/SNF plays no
      role in GAL gene induction. Our finding that chromatin structure is irrelevant
      for repression as studied here-that is, repression sets in as efficiently whether
      or not promoter nucleosomes are allowed to reform-contradicts the widely held,
      but little tested, idea that nucleosomes are required for repression. These
      findings were made possible by our nucleosome occupancy assay. The assay, we
      believe, will prove useful in studying other outstanding issues in the field.

PMID- 19108607
TI  - "It's ok, we're not cousins by blood": the cousin marriage controversy in
      historical perspective.

PMID- 19108606
TI  - PKMzeta maintains spatial, instrumental, and classically conditioned long-term
      memories.
AB  - How long-term memories are stored is a fundamental question in neuroscience. The
      first molecular mechanism for long-term memory storage in the brain was recently
      identified as the persistent action of protein kinase Mzeta (PKMzeta), an
      autonomously active atypical protein kinase C (PKC) isoform critical for the
      maintenance of long-term potentiation (LTP). PKMzeta maintains aversively
      conditioned associations, but what general form of information the kinase encodes
      in the brain is unknown. We first confirmed the specificity of the action of zeta
      inhibitory peptide (ZIP) by disrupting long-term memory for active place
      avoidance with chelerythrine, a second inhibitor of PKMzeta activity. We then
      examined, using ZIP, the effect of PKMzeta inhibition in dorsal hippocampus (DH)
      and basolateral amygdala (BLA) on retention of 1-d-old information acquired in
      the radial arm maze, water maze, inhibitory avoidance, and contextual and cued
      fear conditioning paradigms. In the DH, PKMzeta inhibition selectively disrupted
      retention of information for spatial reference, but not spatial working memory in
      the radial arm maze, and precise, but not coarse spatial information in the water
      maze. Thus retention of accurate spatial, but not procedural and contextual
      information required PKMzeta activity. Similarly, PKMzeta inhibition in the
      hippocampus did not affect contextual information after fear conditioning. In
      contrast, PKMzeta inhibition in the BLA impaired retention of classical
      conditioned stimulus-unconditioned stimulus (CS-US) associations for both
      contextual and auditory fear, as well as instrumentally conditioned inhibitory
      avoidance. PKMzeta inhibition had no effect on postshock freezing, indicating
      fear expression mediated by the BLA remained intact. Thus, persistent PKMzeta
      activity is a general mechanism for both appetitively and aversively motivated
      retention of specific, accurate learned information, but is not required for
      processing contextual, imprecise, or procedural information.

PMID- 19108608
TI  - Towards an integrated framework for assessing the vulnerability of species to
      climate change.

PMID- 19108609
TI  - Nutrient-regulated antisense and intragenic RNAs modulate a signal transduction
      pathway in yeast.
AB  - The budding yeast Saccharomyces cerevisiae alters its gene expression profile in
      response to a change in nutrient availability. The PHO system is a well-studied
      case in the transcriptional regulation responding to nutritional changes in which
      a set of genes (PHO genes) is expressed to activate inorganic phosphate (Pi)
      metabolism for adaptation to Pi starvation. Pi starvation triggers an inhibition
      of Pho85 kinase, leading to migration of unphosphorylated Pho4 transcriptional
      activator into the nucleus and enabling expression of PHO genes. When Pi is
      sufficient, the Pho85 kinase phosphorylates Pho4, thereby excluding it from the
      nucleus and resulting in repression (i.e., lack of transcription) of PHO genes.
      The Pho85 kinase has a role in various cellular functions other than regulation
      of the PHO system in that Pho85 monitors whether environmental conditions are
      adequate for cell growth and represses inadequate (untimely) responses in these
      cellular processes. In contrast, Pho4 appears to activate some genes involved in
      stress response and is required for G1 arrest caused by DNA damage. These facts
      suggest the antagonistic function of these two players on a more general scale
      when yeast cells must cope with stress conditions. To explore general involvement
      of Pho4 in stress response, we tried to identify Pho4-dependent genes by a genome
      wide mapping of Pho4 and Rpo21 binding (Rpo21 being the largest subunit of RNA
      polymerase II) using a yeast tiling array. In the course of this study, we found
      Pi- and Pho4-regulated intragenic and antisense RNAs that could modulate the Pi
      signal transduction pathway. Low-Pi signal is transmitted via certain inositol
      polyphosphate (IP) species (IP7) that are synthesized by Vip1 IP6 kinase. We have
      shown that Pho4 activates the transcription of antisense and intragenic RNAs in
      the KCS1 locus to down-regulate the Kcs1 activity, another IP6 kinase, by
      producing truncated Kcs1 protein via hybrid formation with the KCS1 mRNA and
      translation of the intragenic RNA, thereby enabling Vip1 to utilize more IP6 to
      synthesize IP7 functioning in low-Pi signaling. Because Kcs1 also can
      phosphorylate these IP7 species to synthesize IP8, reduction in Kcs1 activity can
      ensure accumulation of the IP7 species, leading to further stimulation of low-Pi
      signaling (i.e., forming a positive feedback loop). We also report that genes
      apparently not involved in the PHO system are regulated by Pho4 either dependent
      upon or independent of the Pi conditions, and many of the latter genes are
      involved in stress response. In S. cerevisiae, a large-scale cDNA analysis and
      mapping of RNA polymerase II binding using a high-resolution tiling array have
      identified a large number of antisense RNA species whose functions are yet to be
      clarified. Here we have shown that nutrient-regulated antisense and intragenic
      RNAs as well as direct regulation of structural gene transcription function in
      the response to nutrient availability. Our findings also imply that Pho4 is
      present in the nucleus even under high-Pi conditions to activate or repress
      transcription, which challenges our current understanding of Pho4 regulation.

PMID- 19108611
TI  - Caenorhabditis elegans meets microsporidia: the nematode killers from Paris.

PMID- 19108610
TI  - BEAF regulates cell-cycle genes through the controlled deposition of H3K9
      methylation marks into its conserved dual-core binding sites.
AB  - Chromatin insulators/boundary elements share the ability to insulate a transgene
      from its chromosomal context by blocking promiscuous enhancer-promoter
      interactions and heterochromatin spreading. Several insulating factors target
      different DNA consensus sequences, defining distinct subfamilies of insulators.
      Whether each of these families and factors might possess unique cellular
      functions is of particular interest. Here, we combined chromatin
      immunoprecipitations and computational approaches to break down the binding
      signature of the Drosophila boundary element-associated factor (BEAF) subfamily.
      We identify a dual-core BEAF binding signature at 1,720 sites genome-wide,
      defined by five to six BEAF binding motifs bracketing 200 bp AT-rich nuclease
      resistant spacers. Dual-cores are tightly linked to hundreds of genes highly
      enriched in cell-cycle and chromosome organization/segregation annotations. siRNA
      depletion of BEAF from cells leads to cell-cycle and chromosome segregation
      defects. Quantitative RT-PCR analyses in BEAF-depleted cells show that BEAF
      controls the expression of dual core-associated genes, including key cell-cycle
      and chromosome segregation regulators. beaf mutants that impair its insulating
      function by preventing proper interactions of BEAF complexes with the dual-cores
      produce similar effects in embryos. Chromatin immunoprecipitations show that BEAF
      regulates transcriptional activity by restricting the deposition of methylated
      histone H3K9 marks in dual-cores. Our results reveal a novel role for BEAF
      chromatin dual-cores in regulating a distinct set of genes involved in chromosome
      organization/segregation and the cell cycle.

PMID- 19108612
TI  - Copper powder-catalyzed regio- and stereoselective aminobromination of alpha,beta
      unsaturated ketones with TsNH2 and NBS as nitrogen and halogen sources.
AB  - The regio- and stereoselective aminobromination of alpha,beta-unsaturated ketones
      catalyzed by copper powder has been established with 4-TsNH(2) and NBS as the
      nitrogen/bromine sources, respectively. This method provides an easy access for
      preparation of vicinal aminohalo derivatives in the presence of 1 mol % catalyst.
      Electron-rich alpha,beta-unsaturated ketones afforded the corresponding
      aminobrominated products in excellent yields (up to 99.8%), revealing that the
      addition has an electrophilic feature.

PMID- 19108613
TI  - Hydrolysis of 8-quinolyl phosphate monoester: kinetic and theoretical studies of
      the effect of lanthanide ions.
AB  - 8-Quinolyl phosphate (8QP) in the presence of the trivalent lanthanide ions (Ln =
      La, Sm, Eu, Tb, and Er) forms a [Ln x 8QP]+ complex where the lanthanide ion
      catalyzes hydrolysis of 8QP. In reactions with Tb3+ or Er3+, there is evidence of
      limited intervention by a second lanthanide ion. Rate constants are increased by
      more than 10(7)-fold, and kinetic data and B3LYP/ECP calculations indicate that
      the effects are largely driven by leaving group and metaphosphate ion
      stabilization. The lanthanides favor a single-step D(N)A(N) mechanism with a
      dissociative transition state, with limited nucleophilic assistance, consistent
      with the low hydroxide ion dependence and the small kinetic effect of Ln3+ radii.

PMID- 19108614
TI  - Single-chain antibody fragments from a display library derived from chickens
      immunized with a mixture of parasite and viral antigens.
AB  - Phage-displayed chicken single-chain antibody fragment libraries can provide
      useful diagnostic and research reagents. Using avian immunoglobulin genes
      simplifies the construction of such repertoires since far fewer primer sets are
      required to access the avian antibody repertoire than is the case with mice or
      humans. Libraries constructed using mRNA from an immune source are enriched in
      affinity-matured sequences and consequently need not be as large as "universal"
      non-immune repertoires to have a reasonable probability of yielding high-affinity
      binders. Repertoires focused on a number of defined targets can be constructed
      using lymphocyte mRNA from chickens immunized with a mixture of several different
      antigens. This approach was evaluated with the aim of economically and rapidly
      deriving immunodiagnostic reagents for malaria, trypanosomiasis, and malignant
      catarrhal fever, all of which are important to health or food security in Africa.
      Two chickens were each immunized with a mixture comprised of recombinantly
      expressed histidine-rich protein, the aldolase and the lactate dehydrogenase of
      Plasmodium falciparum, the variant surface glycoprotein of Trypanosoma sp., and
      purified malignant catarrhal fever virus, a herpesvirus that causes an
      economically important disease of cattle and other ruminants. Immune responses to
      each of the individual antigens were determined by extracting egg-yolk IgY and
      testing for antigen-specific antibodies in ELISA. The chicken splenocytes were
      then recovered, RNA was extracted, and after reverse transcription, the
      immunoglobulin VH and VL regions were amplified by PCR and joined via a single
      glycyl residue for surface expression on a collection of filamentous
      bacteriophages. The resulting display library was then screened by panning to
      isolate binders. The immunized chickens did not, however, respond equally well to
      all the different antigens, nor was it possible to derive antibody fragments
      against all the targets. These limitations notwithstanding, several useful
      binders with the potential to be used in malaria diagnosis were obtained.

PMID- 19108615
TI  - Production and characterization of monoclonal antibodies to nucleoprotein of
      Marburg virus.
AB  - Monoclonal antibodies (MAbs) against the nucleoprotein of Marburg virus (MARV-NP)
      with high specificity and activity would be useful for the diagnosis of MARV. In
      this report, a recombinant MARV-NP was successfully expressed by an Escherichia
      coli expression system. After immunization and cell fusion, three mouse
      hybridomas (1H4, 2G1, and 3B5) producing MAbs to MARV-NP were established. The
      MAbs obtained were fully characterized using indirect ELISA and Western blot
      analysis. The ELISA results showed that the MAbs' titers were in the range of
      1:6.400 x 10(3) - 1:1.280 x 10(4) in culture fluids, and 1:1.024 x 10(6) -
      1:8.192 x 106 in ascitic fluids. The isotypes of the three MAbs were tested to be
      IgG1(kappa) and all the MAbs recognized the same antigenic epitope. Western blot
      analyses demonstrated that all the MAbs were directed against MARV-NP with the
      affinity constants (Kaff) of about 1.100 x 10(9) M(-1), 1.235 x 10(9) M(-1), and
      1.408 x 10(9) M(-1) for the MAbs 1H4, 2G1, and 3B5, respectively.

PMID- 19108616
TI  - Preparation and characterization of monoclonal antibodies against a
      polysaccharide from Flammulina velutipes mycelium.
AB  - Antigen was synthesized for the preparation of monoclonal antibodies (MAbs)
      against FVP2, a polysaccharide from Flammulina velutipes. FVP2 was coupled to
      bovine serum albumin (BSA) by 1-cyano-4-dimethyl-aminopyridinium
      tetrafluoroborate (CDAP) to produce a neoglycoprotein with the degree of
      substitution (DS; approximately 2.5:1 mol of FVP2 hapten/mol of BSA carrier),
      whose immunogenicity was enhanced in mice. The neoglycoprotein induced vigorous
      primary IgM and booster IgG responses to FVP2. IgG1 was elicited as the dominant
      isotype antibody in BALB/c mice. Then, the MAbs to FVP2 were prepared using
      hybridoma technology. Resulting hybridomas producing anti-FVP2 antibodies were
      screened by indirect enzyme-linked immunosorbent assay (ELISA). As a result,
      three hybridoma cell lines named B11D, C8G, and I6D were acquired, and the
      immunological characteristics of the MAbs were determined.

PMID- 19108617
TI  - Characteristics of an scFv antibody fragment that binds to immunoglobulin G of
      Graves' disease patients and inhibits autoantibody-mediated thyroid-stimulating
      activity.
AB  - Thyroid-stimulating antibodies (TSAbs) are responsible for hyperthyroid Graves'
      disease (GD). Although two peptides that bind to GD immunoglobulin G (IgG), and
      some monoclonal antibodies to the TSH receptor (TSH-R), have been reported to
      inhibit stimulation of cAMP production by patient serum TSAb, our work is the
      first to use phage-display technology to produce a mouse single-chain Fv antibody
      fragment (scFv) that binds to GD IgG and acts as a powerful TSAb (and TSH)
      antagonist. The specificity characteristics and relative affinity (2.8 mol/L) of
      T17 were identified by competitive inhibition ELISA and thiocyanate elution. The
      purified T17 scFv was then tested for its effect on stimulation of cAMP
      production by Graves' patients' sera in TSH receptor-transfected Chinese hamster
      ovary (CHO) cells. T17 was an effective antagonist of TSAb activity in 13 of 16
      patients with GD. In addition, (125)I-TSH binding to TSH-R was also inhibited by
      T17 (57% inhibition at 1 mg/mL). This new scFv suggests in vitro applications
      such as purification of TSAb or diagnosis of GD. In addition, it may have in vivo
      usefulness such as treatment of TSH-R mediated ophthalmic symptoms of Graves'
      disease.

PMID- 19108618
TI  - Monoclonal antibodies to LipL32 protect against heterologous Leptospira spp.
      challenge.
AB  - A non-culture-based leptospirosis vaccine that cross-protects against infection
      caused by heterologous Leptospira spp. should replace the currently available
      products, which are qualitatively and quantitatively inadequate. With that in
      mind, two murine hybridomas secreting monoclonal antibodies (MAb) binding only to
      homogenates of pathogenic Leptospira spp., and not of the saprophytic L. biflexa,
      serogroup Patoc, serovar Patoc, were produced. The MAbs of both clones
      neutralized Leptospira-mediated human red blood cell lysis in vitro and rescued
      hamsters from lethal infection with heterologous Leptospira spp. The orthologous
      Leptospira spp. protein carrying the MAb epitope(s) was identified by two
      dimensional gel electrophoresis (2DE)-based proteomics and database search. The
      epitopes of the MAbs were located on the major outer membrane protein LipL32 of
      the pathogenic Leptospira spp. The MAbs in their humanized version are potential
      leptospirosis immunotherapeutics. They are also suitable as detection reagents in
      antigen-based assays for the rapid diagnosis of leptospirosis. Recombinant LipL32
      is a good candidate for a broad spectrum, non-culture-based leptospirosis
      vaccine.

PMID- 19108619
TI  - Production of a monoclonal antibody against non-structural protein 3 of dengue-2
      virus by intrasplenic injection.
AB  - Dengue fever and dengue hemorrhagic fever/dengue shock syndrome are highly
      infectious diseases caused by dengue virus (DV). DV non-structural protein 3
      (NS3) is known to possess ATPase, helicase, and protease activity that is a
      constitutive part of the replication complex of DV. In this study, we discuss the
      cloning, expression, and purification of the DV-2 NS3 protein to immunize mice by
      intrasplenic injection and then to generate a monoclonal antibody (MAb). One MAb,
      named 4F5, was obtained and it was specific to NS3 of DV-2. Immunofluorescence
      show that 4F5 recognizes the native protein in infected ECV304 cells. Likewise,
      C6/36-infected lysates were used in Western blot analysis, and we observed the
      specific characteristic band that defines NS3. We conclude that MAb 4F5 may be a
      useful tool, not only to study the replicative process of DV, but also to
      generate specific diagnostic tools for DV infection.

PMID- 19108620
TI  - Development of two murine monoclonal antibodies recognizing human nG1m(a)-like
      isoallotypic markers.
AB  - Antigenic determinants of immunoglobulin molecules are categorized into three
      groups: idiotypes, isotypes, and allotypes. An isoallotype is defined as an
      isotypic determinant in one or more subclasses and an allotype in another
      subclass of a given isotype. The isoallotype nG1m(a), formerly called non-a, is
      an allotype located on human IgG1 molecules lacking the G1m(a) allotype. This
      marker, however, is also detectable on all human IgG2 and IgG3 molecules. Anti
      isoallotypic antibodies are useful tools for structural studies of
      immunoglobulins, forensic science, and epidemiological demographic
      investigations. In this study, two murine monoclonal antibodies (MAbs)
      recognizing nG1m(a)-like epitope(s) were generated against a human IgG myeloma
      protein. These MAbs are produced by hybridoma clones (4F18B12 and 6F18D1)
      obtained by fusion of SP2/0 myeloma cells with splenocytes from BALB/c mice
      immunized with heavy chain of a human IgG3 myeloma protein. These MAbs reacted
      with Fc, but not Fab fragment of the immunizing IgG3 paraprotein. Specificity of
      the MAbs was further analyzed using a panel of purified myeloma proteins and
      polyclonal IgG3, including IgG1 (n = 9), IgG2 (n = 4), IgG3 (n = 8), and IgG4 (n
      = 6) subclasses. Our results demonstrated that these MAbs reacted with linear
      epitope(s) located on heavy chain of all IgG2 and IgG3 molecules tested and some
      paraproteins of IgG1 subclass, but none of the IgG4 molecules. So these MAbs seem
      to recognize nG1m(a)-like isoallotypic marker. These MAbs showed no cross
      reactivity with serum of other species tested. Both MAbs belonged to IgG1
      subclass with affinity constants of 4.5 x 10(9) mol(-1) (4F18B12) and 3.46 x
      10(9) mol(-1) (6F18D1), respectively. These MAbs might be used as a tool to
      detect nG1m(a) + IgG molecules.

PMID- 19108621
TI  - Production of polyclonal antibody against alkyl hydroperoxide reductase of
      Helicobacter pylori and its antigenicity.
AB  - Stool-antigen detection kits for diagnosis of Helicobacter pylori infection have
      been widely used because of their full non-invasive nature. Because Helicobacter
      pylori strains show a distinctive genetic diversity, it is important to find a
      protein that is a common antigen of various strains and shows a strong
      immunogenicity for the development of a stool- antigen detection kit. Alkyl
      hydroperoxide reductase (AhpC) of Helicobacter pylori strongly reacts with the
      sera of patients with gastritis and peptic ulcer. Therefore, AhpC seems to be an
      excellent candidate as a target protein for this study. Accordingly, polyclonal
      antiserum against AhpC was produced in adult New Zealand white rabbits by using
      AhpC in the gel bands without adding Freund's adjuvant. In addition, isolation
      and purification of AhpC were perfomed by preparative sodium dodecyl sulfate
      polyacrylamide gel electrophoresis and electroelution. In this study, a simple
      method was used for rapid production of polyclonal antibody against AhpC of H.
      pylori, which avoids both the long-term AhpC purification and the addition of
      Freund's adjuvant. One-dimensional preparative gel electrophoresis allows a
      single and short purification step; the high-resolution capacity of this
      technique leads to a high level of purity of the protein and consequently to a
      very high specificity of the antibody. Moreover, this method avoids contamination
      by other non-specific proteins, which often appear during the purification
      process by column chromatographic techniques, which may also decrease the purity
      of the immunogen. The present method is simple, rapid and cost-effective, and
      also makes it possible to produce antibody for stool-antigen enzyme immunoassay
      in a short time and at low cost.

PMID- 19108622
TI  - A rapid opsonic assay for measuring killing of bioluminescent Staphylococcus
      epidermidis.
AB  - The ability to measure the opsonic activity of antibody may be critical in
      choosing among potential therapeutic candidates. It has been shown in numerous
      studies that the ability of antibody to mediate clearance of bacterial organisms
      in animal models and in humans is related to its in vitro opsonic activity and
      not solely to its antigen binding activity. We have developed a rapid and robot
      adaptable opsonophagocytosis assay for Staphylococci based on bioluminescence
      produced by bacteria transfected with the luciferase operon. Opsonophagocytosis
      is measured by the loss of bioluminescence as bacteria are opsonized by
      phagocytes and killed. Pagibaximab is a humanized monoclonal anti-lipoteichoic
      acid (LTA) antibody opsonic for S. epidermidis and S. aureus, which we used to
      develop this rapid bioluminescence assay.

PMID- 19108623
TI  - Sequence analysis of cDNAs encoding the heavy and light chain variable regions of
      a WSSV-neutralizing monoclonal antibody.
AB  - Antibodies raised against individual viral envelope proteins have been used in
      white spot syndrome virus (WSSV) neutralization assays. We report here the
      sequence analysis of cDNAs encoding the variable regions of a novel monoclonal
      antibody that binds to the viral envelope protein and neutralizes WSSV infection.
      The heavy and light variable chains are most homologous to VH7183 germline gene
      (AF120472) and IgVk RF germline gene (AJ235936), respectively. Database searches
      using the derived sequences predicted residues comprising CDR loops. The 12 amino
      acid residue of the heavy chain CDR3 is rich in negatively charged aspartic acid
      (25%) and did not show significant homology to any murine V gene available on the
      database. This study provides insights on the paratope-epitope interaction and
      can be used to identify compounds with comparable properties as the paratope
      leading to future development of drugs and vaccines for WSSV infection.

PMID- 19108631
TI  - Mo(CO)6-mediated intramolecular Pauson-Khand reaction of substituted diethyl 3
      allyloxy-1-propynylphosphonates.
AB  - Cyclisation of diethyl 3-allyloxy-1-propynylphosphonates with Mo(CO)(6) under PK
      conditions to give 3-substituted-5-oxo-3,5,6,6a-tetrahydro-1H-cyclopenta[c]furan
      4-ylphosphonate, 2a-h, in 45-88% isolated yields was done. The R groups are
      always syn with H(b) (where applicable). The stereochemistry was determined via
      both NMR and crystal X-ray analysis.

PMID- 19108632
TI  - Zinc-catalyzed nucleophilic substitution reaction of chlorosilanes with
      organomagnesium reagents.
AB  - Zinc-catalyzed nucleophilic substitution reactions of chlorosilanes with
      organomagnesium reagents afford various tetraorganosilanes under mild reaction
      conditions. The reactions can be performed on large scale and allow efficient
      preparation of functionalized tetraorganosilanes.

PMID- 19108633
TI  - Gas chromatography/surface-assisted laser desorption ionization mass spectrometry
      of amphetamine-like compounds.
AB  - A variety of amphetamine-like compounds were analyzed by gas
      chromatography/surface-assisted laser desorption ionization mass spectrometry,
      GC/SALDI-MS. In the SALDI method, compounds are adsorbed on a solid SALDI
      substrate and directly ionized from the substrate by means of a laser pulse. The
      interfacing of a SALDI ion source with a gas chromatograph is presented here for
      the first time. The end of the GC column is situated 20 mm from the silicon
      substrate in the vacuum of the ion source of a time-of-flight mass spectrometer,
      and the compounds eluted from the GC capillary are adsorbed onto the
      nanostructured silicon surface. The mass spectra show very low levels of
      background noise and no reagent ions. GC/SALDI-MS detection limits are several
      orders of magnitude lower than those previously reported for GC/MS analysis of
      amphetamine-like compounds. The extent of fragmentation is under experimental
      control by changing the laser fluence.

PMID- 19108634
TI  - An automatic solid-phase synthesis of peptaibols.
AB  - An automated approach to peptaibols using microwave-assisted solid-phase peptide
      synthesis is demonstrated with a combination of HBTU and acid fluoride mediated
      couplings for normal and alpha,alpha-dialkylated amino acids, respectively. The
      method is utilized for the automated synthesis of several full-length peptaibols,
      including alamethicin, tylopeptin, ampullosporin, bergofungin, cervinin,
      trikoningin, trichogin, and peptaibolin, reducing both synthesis time and costs
      significantly as compared to other approaches. Furthermore, the use of
      noncommercially available reagents is minimized.

PMID- 19108635
TI  - EPR evidence of cyanide binding to the Mn(Mg) center of cytochrome c oxidase:
      support for Cu(A)-Mg involvement in proton pumping.
AB  - We examined the anion binding behavior of the Mg(Mn) site in cytochrome c oxidase
      to test a possible role of this center in proton pumping. Rhodobacter sphaeroides
      grown in a Mn(II)-rich medium replaces the intrinsic Mg(II) ion with an EPR
      detectable Mn(II) ion without change in activity. Due to its close proximity and
      a shared ligand, oxidized Cu(A) is spin-coupled to the Mn(II) ion, affecting the
      EPR spectrum. An examination of both bovine and R.s. oxidase crystal structures
      reveals a hydrogen-bonding pattern in the vicinity of the Mg(II) site that is
      consistent with three water ligands of the Mg(Mn) center when Cu(A) is oxidized.
      In the reduced structure, one water molecule in the vicinity of the Cu(A) ligand,
      E198, moves closer, appearing to be converted into an ionically bonded hydronium
      ion, while a second water molecule bonded to Mg(Mn) shows evidence of conversion
      to a hydroxide. The implied proton movement is proposed to be part of a redox
      linked export of a pumped proton from the binuclear center into the exit pathway.
      To test the model, cyanide and azide were added to the oxidized and reduced forms
      of the enzyme, and Mn(II) CW-EPR and ESEEM spectra were recorded. Addition of
      azide broadened the CW-EPR spectra for both oxidized and reduced enzyme. Cyanide
      addition affected the Mn(II) CW-EPR spectrum of reduced cytochrome c oxidase by
      increasing Mn(II) zero field splitting and broadening the spectral line shapes
      but had no effect on oxidized enzyme. ESEEM measurements support a differential
      ability of Mn(II) to bind cyanide in the reduced state of cytochrome c oxidase.
      This new observation of anion binding at the Mg/Mn site is of interest in terms
      of accessibility of the buried site and its potential role in redox-dependent
      proton pumping.

PMID- 19108639
TI  - Hydrogen-bonding structure and dynamics of aqueous carbonate species from car
      parrinello molecular dynamics simulations.
AB  - A comprehensive Car-Parrinello molecular dynamics (CP-MD) study of aqueous
      solutions of carbonic acid (H(2)CO(3)), bicarbonate (HCO(3)(-)), carbonate
      (CO(3)(2-)), and carbon dioxide (CO(2)) provides new quantitative insight into
      the structural and dynamic aspects of the hydrogen-bonding environments for these
      important aqueous species and their effects on the structure, H-bonding, and
      dynamical behavior of the surrounding water molecules. The hydration structures
      of the different carbonate species depend on their ability to accept and donate H
      bonds with H(2)O. The H-bonds donated by the C-O-H sites of the carbonate species
      to water molecules are generally stronger and longer-lived than those accepted by
      these sites from water molecules. The structural relaxation among the water
      molecules is dominated by diffusional (translational) motion of H(2)O, whereas
      the H-bond reorganization is dominated by the librational motion of the water
      molecules and the carbonate species. The rates of structural relaxation of the
      H(2)O molecules and the rates of H-bond reorganization among them are slower in
      systems containing carbonate species, consistent with previous studies of simple
      salt solutions. The strengths and lifetimes of H-bonds involving the carbonate
      species positively correlate with the total negative charge on the species. H
      bond donation from H(2)O to CO(2) is weak, but the presence of CO(2) noticeably
      affects the structure and structural relaxation of the surrounding H-bonding
      network leading to generally stronger H-bonds and slower relaxation rates, the
      behavior typical of a hydrophobic solute.

PMID- 19108636
TI  - Functionalized 2'-amino-alpha-L-LNA: directed positioning of intercalators for
      DNA targeting.
AB  - Chemically modified oligonucleotides are increasingly applied in nucleic acid
      based therapeutics and diagnostics. LNA (locked nucleic acid) and its
      diastereomer alpha-L-LNA are two promising examples thereof that exhibit
      increased thermal and enzymatic stability. Herein, the synthesis, biophysical
      characterization, and molecular modeling of N2'-functionalized 2'-amino-alpha-L
      LNA is described. Chemoselective N2'-functionalization of protected amino alcohol
      1 followed by phosphitylation afforded a structurally varied set of target
      phosphoramidites, which were incorporated into oligodeoxyribonucleotides.
      Incorporation of pyrene-functionalized building blocks such as 2'-N-(pyren-1
      yl)carbonyl-2'-amino-alpha-L-LNA (monomer X) led to extraordinary increases in
      thermal affinity of up to +19.5 degrees C per modification against DNA targets in
      particular. In contrast, incorporation of building blocks with small nonaromatic
      N2'-functionalities such as 2'-N-acetyl-2'-amino-alpha-L-LNA (monomer V) had
      detrimental effects on thermal affinity toward DNA/RNA complements with decreases
      of as much as -16.5 degrees C per modification. Extensive thermal DNA
      selectivity, favorable entropic contributions upon duplex formation,
      hybridization-induced bathochromic shifts of pyrene absorption maxima and
      increases in circular dichroism signal intensity, and molecular modeling studies
      suggest that pyrene-functionalized 2'-amino-alpha-L-LNA monomers W-Y having short
      linkers between the bicyclic skeleton and the pyrene moiety allow high-affinity
      hybridization with DNA complements and precise positioning of intercalators in
      nucleic acid duplexes. This rigorous positional control has been utilized for the
      development of probes for emerging therapeutic and diagnostic applications
      focusing on DNA targeting.

PMID- 19108640
TI  - Dynamics of carbon monoxide photodissociation in Bradyrhizobium japonicum FixL
      probed by picosecond midinfrared spectroscopy.
AB  - The FixL proteins are heme-based bacterial oxygen sensors, distinct from globins
      in structure and ligand binding properties. To better understand the dynamics of
      ligand dissociation and binding within the PAS domain fold of FixL, we have
      carried out picosecond visible pump-midinfrared probe spectroscopy on the
      isolated PAS domain of FixL from Bradyrhizobium japonicum. We employ the diatomic
      ligand CO as a probe of the ligand-dissociation pocket dynamics; upon
      photoexcitation with a visible laser pulse, CO is released and the infrared
      active stretch frequency of the CO molecule changes, as it is very sensitive to
      interactions with the surrounding protein. The infrared absorption difference
      spectra indicate that the escape of photolyzed CO to solvent is preceded by
      transient docking within the protein in a manner similar to globins. A small
      scale spectral change of the CO molecule on a picosecond time scale is likely due
      to changes in heme-protein conformation associated with cooling. A larger scale
      spectral evolution on a nanosecond time scale indicates a structural change in
      the protein, possibly related to changes in the beta-strands associated with the
      transition from CO-bound to deoxy in BjFixLH (Key, J.; Srajer, V.; Pahl, R.;
      Moffat, K. Biochemistry 2007, 46, 4706).

PMID- 19108638
TI  - Close proximity of myosin loop 3 to troponin determined by triangulation of
      resonance energy transfer distance measurements.
AB  - Cooperative activation of the thin filament is known to be influenced by the
      tight binding of myosin to actin, but the molecular mechanism underlying this
      contribution of myosin is not well understood. To better understand the
      structural relationship of myosin with the regulatory troponin complex, resonance
      energy transfer measurements were used to map the location of troponin relative
      to a neighboring myosin bound to actin using atomic models. Using a chicken
      troponin T isoform that contains a single cysteine near the binding interface
      between troponins T, I, and C, this uniquely labeled cysteine on troponin was
      found to be remarkably near loop 3 of myosin. This loop has previously been
      localized near the actin and myosin interface by chemical cross-linking methods,
      but its functional contributions have not been established. The implications of
      this close proximity are examined by molecular modeling, which suggests that only
      restricted conformations of actomyosin can accommodate the presence of troponin
      at this location near the cross-bridge. This potential for interaction between
      troponin and myosin heads that bind near it along the thin filament raises the
      possibility of models in which direct myosin and troponin interactions may play a
      role in the regulatory mechanism.

PMID- 19108642
TI  - Temperature scaling method for Markov chains.
AB  - The use of ab initio potentials in Monte Carlo simulations aimed at investigating
      the nucleation kinetics of water clusters is complicated by the computational
      expense of the potential energy determinations. Furthermore, the common desire to
      investigate the temperature dependence of kinetic properties leads to an urgent
      need to reduce the expense of performing simulations at many different
      temperatures. A method is detailed that allows a Markov chain (obtained via Monte
      Carlo) at one temperature to be scaled to other temperatures of interest without
      the need to perform additional large simulations. This Markov chain temperature
      scaling (TeS) can be generally applied to simulations geared for numerous
      applications. This paper shows the quality of results which can be obtained by
      TeS and the possible quantities which may be extracted from scaled Markov chains.
      Results are obtained for a 1-D analytical potential for which the exact solutions
      are known. Also, this method is applied to water clusters consisting of between 2
      and 5 monomers, using Dynamical Nucleation Theory to determine the evaporation
      rate constant for monomer loss. Although ab initio potentials are not utilized in
      this paper, the benefit of this method is made apparent by using the Dang-Chang
      polarizable classical potential for water to obtain statistical properties at
      various temperatures.

PMID- 19108641
TI  - Translesion DNA synthesis by human DNA polymerase eta on templates containing a
      pyrimidopurinone deoxyguanosine adduct, 3-(2'-deoxy-beta-d-erythro
      pentofuranosyl)pyrimido-[1,2-a]purin-10(3H)-one.
AB  - M(1)dG (3-(2'-deoxy-beta-d-erythro-pentofuranosyl)pyrimido[1,2-a]purin-10(3H)
      one) lesions are mutagenic in bacterial and mammalian cells, leading to base
      substitutions (mostly M(1)dG to dT and M(1)dG to dA) and frameshift mutations.
      M(1)dG is produced endogenously through the reaction of peroxidation products,
      base propenal or malondialdehyde, with deoxyguanosine residues in DNA. The
      mutagenicity of M(1)dG in Escherichia coli is dependent on the SOS response,
      specifically the umuC and umuD gene products, suggesting that mutagenic lesion
      bypass occurs by the action of translesion DNA polymerases, like DNA polymerase
      V. Bypass of DNA lesions by translesion DNA polymerases is conserved in bacteria,
      yeast, and mammalian cells. The ability of recombinant human DNA polymerase eta
      to synthesize DNA across from M(1)dG was studied. M(1)dG partially blocked DNA
      synthesis by polymerase eta. Using steady-state kinetics, we found that insertion
      of dCTP was the least favored insertion product opposite the M(1)dG lesion (800
      fold less efficient than opposite dG). Extension from M(1)dG.dC was equally as
      efficient as from control primer-templates (dG.dC). dATP insertion opposite
      M(1)dG was the most favored insertion product (8-fold less efficient than
      opposite dG), but extension from M(1)dG.dA was 20-fold less efficient than dG.dC.
      The sequences of full-length human DNA polymerase eta bypass products of M(1)dG
      were determined by LC-ESI/MS/MS. Bypass products contained incorporation of dA
      (52%) or dC (16%) opposite M(1)dG or -1 frameshifts at the lesion site (31%).
      Human DNA polymerase eta bypass may lead to M(1)dG to dT and frameshift but
      likely not M(1)dG to dA mutations during DNA replication.

PMID- 19108643
TI  - Dynamics of the conformational transitions in the assembling of the Michaelis
      complex of a bisubstrate enzyme: a (15)N relaxation study of Escherichia coli 6
      hydroxymethyl-7,8-dihydropterin pyrophosphokinase.
AB  - 6-Hydroxymethyl-7,8-dihydropterin pyrophosphokinase (HPPK) catalyzes the transfer
      of pyrophosphate from ATP to 6-hydroxymethyl-7,8-dihydropterin (HP), which
      follows an ordered bi-bi kinetic mechanism with ATP binding to the enzyme first.
      HPPK undergoes dramatic conformational changes during its catalytic cycle as
      revealed by X-ray crystallography, and the conformational changes are essential
      for the enzymatic catalysis as shown by site-directed mutagenesis and biochemical
      and crystallographic analysis of the mutants. However, the dynamic properties of
      the enzyme have not been measured experimentally. Here, we report a (15)N NMR
      relaxation study of the dynamic properties of Escherichia coli HPPK from the apo
      form to the binary substrate complex with MgATP (represented by MgAMPCPP, an ATP
      analogue) to the Michaelis complex (ternary substrate complex) with MgATP
      (represented by MgAMPCPP) and HP (represented by 7,7-dimethyl-6-hydroxypterin, an
      HP analogue). The results show that the binding of the nucleotide to HPPK does
      not cause major changes in the dynamic properties of the enzyme. Whereas enzymes
      are often more rigid when bound to the ligand or the substrate, the internal
      mobility of HPPK is not reduced and is even moderately increased in the binary
      complex, particularly in the catalytic loops. The internal mobility of the
      catalytic loops is significantly quenched upon the formation of the ternary
      complex, but some mobility remains. The enhanced motions in the catalytic loops
      of the binary substrate complex may be required for the assembling of the ternary
      complex. On the other hand, some degrees of mobility in the catalytic loops of
      the ternary complex may be required for the optimal stabilization of the
      transition state, which may need the instantaneous adjustment and alignment of
      the side-chain positions of catalytic residues. Such dynamic behaviors may be
      characteristic of bisubstrate enzymes.

PMID- 19108645
TI  - Partners in advancing care and education solutions study: impact on processes and
      outcomes of diabetes care.
AB  - This study evaluated a comprehensive approach to clinical care, Staged Diabetes
      Management, and a curriculum to facilitate optimum self-care, Type 2 Diabetes
      BASICS. The goal was to meet the Diabetes Physician Recognition Program (DFRP)
      and Education Recognition Program (ERP) criteria. Baseline chart audits were used
      to identify areas for improvement. Multiple methods were employed to train
      clinicians and staff and address organizational issues. Improvements in care were
      supported through consultation and repeated measurements and incentives. Eight
      centers completed training and submitted final data. None of the centers met DPRP
      recognition criteria at baseline; 3 centers already had ERP certification. After
      completing the program, all centers received DPRP and ERP certification. The
      greatest improvements occurred in documentation of eye and foot examinations. The
      Partners in Advancing Care and Education Solutions Study, or PACES, program was
      associated with significant improvements in diabetes care in diverse settings.
      Focusing on process deficiencies led to significant improvements, and spillover
      improvements were apparent in the outcome indicators.

PMID- 19108644
TI  - The impact of an integrated population health enhancement and disease management
      program on employee health risk, health conditions, and productivity.
AB  - This study evaluated the impact of an integrated population health enhancement
      program on employee health risks, health conditions, and productivity.
      Specifically, we analyzed changes in these measures among a cohort of 543
      employees who completed a health risk assessment in both 2003 and 2005. We
      compared these findings with 2 different sets of employees who were not offered
      health enhancement programming. We found that the DIRECTV cohort showed a
      significant reduction in health risks after exposure to the program. Relative to
      a matched comparison group, the proportion of low-risk employees at DIRECTV in
      2005 was 8.2 percentage points higher; the proportion of medium-risk employees
      was 7.1 percentage points lower; and the proportion of high-risk employees was
      1.1 percentage points lower (p < 0.001). The most noticeable changes in health
      risk were a reduction in the proportion of employees with high cholesterol; an
      improvement in diet; a reduction of heavy drinking; management of high blood
      pressure; improved stress management; increased exercise; fewer smokers; and a
      drop in obesity rates. We also found that a majority of employees who improved
      their risk levels from 2003 to 2005 maintained their gains in 2006. Employees who
      improved their risks levels also demonstrated relative improvement in
      absenteeism. Overall, this study provides additional evidence that integrated
      population health enhancement positively impacts employees' health risk and
      productivity; it also reinforces the view that "good health is good business."

PMID- 19108646
TI  - Random fluctuations and validity in measuring disease management effectiveness
      for small populations.
AB  - One objective of a disease management (DM) program is the reduction of members'
      claims costs. A considerable amount of effort has been dedicated to standardizing
      the outcomes of DM measurement. An area that has not received as much attention
      is that of random fluctuations in measured outcomes and the related issue of the
      validity of outcomes subject to random fluctuation. From year to year, large
      random fluctuations in claims costs can increase or reduce actual savings from a
      DM program. Sponsors of DM programs want to know how large a group or sample is
      necessary to prevent the effect of random fluctuations from overwhelming the
      effect of claims reductions. In this paper, we measure the fluctuations in
      calculated DM savings in a large commercial population using an adjusted
      historical control methodology--the methodology that has become the industry
      standard and which is codified by DMAA's Guidelines. We then determine the sample
      size necessary to demonstrate DM program savings at different levels of
      confidence and model the effect on fluctuations in observed outcomes under
      different methods of choosing trend, different levels of truncation, and for
      different estimates of program savings. Some groups, particularly employers, will
      be smaller than the minimum size required for credible outcomes measurement. For
      groups smaller than this minimum size, we suggest a utilization-based outcomes
      measure that can be used as a proxy. For both claims- and utilization-based
      calculations, we provide confidence intervals to be placed around savings
      estimates. We do this for group sizes ranging from 1000 to 100,000 members.

PMID- 19108647
TI  - Painful diabetic peripheral neuropathy in a managed care setting: patient
      identification, prevalence estimates, and pharmacy utilization patterns.
AB  - The objectives of this study were to validate an algorithm for identifying
      patients with painful diabetic peripheral neuropathy (pDPN) and demonstrate its
      practical applications. Using the Kaiser Permanente Colorado Diabetes Registry,
      an algorithm was developed with selected ICD-9 diagnosis codes combined with
      automated pharmacy data for medications prescribed for pDPN symptoms. Medical
      records were reviewed to confirm pDPN presence and to inform algorithm
      refinement. Prevalence was estimated with a numerator of members with diabetes
      who had inclusion but no exclusion codes in 2003 (Method 1) and with a numerator
      of diabetes patients with inclusion codes between 1998 and 2003 who had no
      subsequent exclusion codes and who remained members in 2003 (Method 2); the
      denominator was all members with diabetes in 2003. Medication utilization was
      compared between patients with and without pDPN. A total of 19,577 members with
      diabetes were identified; 2612 met initial inclusion criteria. Medical record
      review (n = 298) demonstrated sensitivity of 94%, specificity of 55%, and
      positive predictive value (PPV) of 64%. Inclusion criteria were modified and
      pharmacy data eliminated. The revised algorithm identified 1754 additional
      patients meeting inclusion criteria. Medical record review (n = 190) demonstrated
      sensitivity of 99%, specificity of 49%, and PPV of 79%. Using the validated
      algorithm, pDPN prevalence was 113 (Method 1) and 208 (Method 2) per 1000 persons
      with diabetes. Significant differences were observed in medication prescriptions
      between patients with and without pDPN. Estimated pDPN prevalence among persons
      with diabetes was 11%-21% and pDPN patients had greater utilization of selected
      medications than those without pDPN. Identifying patients with pDPN is a
      fundamental step for improving disease management and understanding the economic
      impact of pDPN.

PMID- 19108648
TI  - An assessment of patient education and self-management in diabetes disease
      management--two case studies.
AB  - Diabetes affects 7.8% of Americans, nearly 24 million people, and costs $174
      billion yearly. People with diabetes benefit from self-management; disease
      management (DM) programs are effective in managing populations with diabetes.
      Little has been published on the intersection of diabetes education and DM. Our
      hypothesis was that diabetes educators and their interventions integrate well
      with DM and effectively support providers' care delivery. A literature review was
      conducted for papers published within the past 3 years and identified using the
      search terms "diabetes educator" and "disease management." Those that primarily
      addressed community health workers or the primary care/community setting were
      excluded. Two case studies were conducted to augment the literature. Ten of 30
      manuscripts identified in the literature review were applicable and indicate that
      techniques and interventions based on cognitive theories and behavioral change
      can be effective when coupled with diabetes DM. Better diabetes self-management
      through diabetes education encourages participation in DM programs and adherence
      to recommended care in programs offered by DM organizations or those that are
      provider based. Improved health outcomes and reduced cost can be achieved by
      blending diabetes education and DM. Diabetes educators are a critical part of the
      management team and, with their arsenal of goal setting and behavior change
      techniques, are an essential component for the success of diabetes DM programs.
      Additional research needs to be undertaken to identify effective ways to
      integrate diabetes educators and education into DM and to assess clinical,
      behavioral, and economic outcomes arising from such programs.

PMID- 19108649
TI  - The Chronic Care Model for behavioral health care.
AB  - This paper describes the successful application of the Chronic Care Model (CCM)
      at Touchstone innovare, a large mental health agency serving a population of
      persons with a serious psychiatric condition. Based on our experience with the
      CCM, it is proposed that it could be applied in behavioral health care in the
      same manner as it is in physical health care. It is our contention that "chronic
      condition" should be the key phrase, and that there should not be a distinction
      in the application of a treatment model, whether the chronic condition is
      behavioral or physical.

PMID- 19108650
TI  - Comparing predicted risk reports and health risk assessments in Medicaid.

PMID- 19108652
TI  - Endohedral nickel, palladium, and platinum atoms in 10-vertex germanium clusters:
      competition between bicapped square antiprismatic and pentagonal prismatic
      structures.
AB  - Density functional theory predicts significant differences in the preferred
      structures of endohedral M@Ge10z (M = Ni, Pd, Pt; z = 0, 2-, 4-) clusters upon a
      change of the central metal atom in otherwise isoelectronic systems. For the
      neutral clusters M@Ge10 the global minima are singlet bicapped square antiprisms.
      However, triplet regular pentagonal prismatic structures become increasingly
      energetically competitive in the series Ni --> Pd -> Pt. The pentagonal prismatic
      dianions M@Ge10(2-) (M = Ni, Pd, Pt) appear to have closed shell structures and
      are the global minima for palladium and platinum. However, the global minimum for
      Ni@Ge102- is the capped square antiprism suggested by the Wade-Mingos rules. A
      number of singlet low-energy unsymmetrical structures are found for the
      tetraanions M@Ge10(4-). However, for the palladium and platinum tetraanions
      triplet pentagonal prismatic structures are energetically competitive with the
      unsymmetrical structures.

PMID- 19108654
TI  - Metabolic soft spot identification and compound optimization in early discovery
      phases using MetaSite and LC-MS/MS validation.
AB  - Metabolic stability is a key property to enable drugs to reach therapeutic
      concentrations. Microsomal clearance assays are used to dial out labile compounds
      in early discovery phases. However, because they do not provide any information
      on soft spots, the rational design of more stable compounds remains challenging.
      A robust soft spot identification procedure combining in silico prediction
      ranking using MetaSite and mass-spectrometric confirmation is described.
      MetaSite's first rank order predictions were experimentally confirmed for only
      about 55% of the compounds. For another 29% of the compounds, the second (20%) or
      the third (9%) rank order predictions were detected. This automatic and high
      throughput reprioritization of a likely soft-spot increases the likelihood of
      working on the right soft spot from about 50% to more than 80%. With this
      information, the structure-metabolism relationships are likely to be understood
      faster and earlier in drug discovery.

PMID- 19108656
TI  - Electronic transport in superlattice-structured ZnO Nanohelix.
AB  - Superlattice-structured ZnO nanohelix is a structure that is made of a coiling
      nanobelt, which is composed of ZnO nanostripes oriented alternatively in two
      different orientations (Science 2005, 309, 1700). The nanostripes run almost in
      parallel to the nanobelt direction but at an offset angle of approximately 5
      degrees . We have measured the transport properties of a nanohelix and found its
      abnormal nonlinear characteristic. In comparison to the Ohmic transport property
      of a single crystal ZnO nanobelt measured under the same experimental conditions,
      the symmetric "Schottky-type" I-V property of the nanohelix is suggested due to
      nanostripe boundaries and surfaces, where built-in periodic back-to-back energy
      barriers might occur across the nanostripe interfaces as a result of polar
      charges and interface-strain-induced piezoelectric effect. The effective
      potential barrier across the nanostripe boundary is estimated to be approximately
      24 meV. With the increasing of bias voltage, electrons can effectively tunnel
      through and thermionic emission across nanostripe boundaries, leading to a fast
      increase in transport current. It is suggested that the ZnO nanohelix could form
      a new type of band structure modulated superlattice for fabricating novel
      electronic devices.

PMID- 19108655
TI  - Multivalent scaffolds for affinity maturation of small molecule cell surface
      binders and their application to prostate tumor targeting.
AB  - Adamantane scaffolds for affinity maturation of prostate cancer specific ligands
      of low molecular mass are described. These scaffolds are modular and can be used
      for conjugation of up to three ligands and an additional effector molecule by
      standard peptide coupling techniques. The potential of the scaffolds is
      demonstrated with the multimerization of GPI 1, a prostate cancer specific small
      molecule. A detailed study of multimerized GPI conjugates with near-infrared
      fluorophores and their binding properties to different prostate cancer cell lines
      shows the specific binding of these conjugates to cell types positive for
      prostate specific membrane antigen (PSMA). We demonstrate that these conjugates
      allow the sensitive imaging of prostate cancer cells with NIR methodology and
      suggest that our adamantane scaffolds might be generally useful for affinity
      maturation of small molecules targeting cell surface epitopes.

PMID- 19108658
TI  - Neurobiology of pediatric mood disorders: are we there yet?

PMID- 19108659
TI  - Orbitofrontal cortex volumes in medication naive children with major depressive
      disorder: a magnetic resonance imaging study.
AB  - OBJECTIVES: Adults with major depressive disorder (MDD) are reported to have
      reduced orbitofrontal cortex (OFC) volumes, which could be related to decreased
      neuronal density. We conducted a study on medication naive children with MDD to
      determine whether abnormalities of OFC are present early in the illness course.
      METHODS: Twenty seven medication naive pediatric Diagnostic and Statistical
      Manual of Mental Disorders, 4(th) edition (DSM-IV) MDD patients (mean age +/- SD
      = 14.4 +/- 2.2 years; 10 males) and 26 healthy controls (mean age +/- SD = 14.4
      +/- 2.4 years; 12 males) underwent a 1.5T magnetic resonance imaging (MRI) with
      3D spoiled gradient recalled acquisition. The OFC volumes were compared using
      analysis of covariance with age, gender, and total brain volume as covariates.
      RESULTS: There was no significant difference in either total OFC volume or total
      gray matter OFC volume between MDD patients and healthy controls. Exploratory
      analysis revealed that patients had unexpectedly larger total right lateral (F =
      4.2, df = 1, 48, p = 0.05) and right lateral gray matter (F = 4.6, df = 1, 48, p
      = 0.04) OFC volumes compared to healthy controls, but this finding was not
      significant following statistical correction for multiple comparisons. No other
      OFC subregions showed a significant difference. CONCLUSIONS: The lack of OFC
      volume abnormalities in pediatric MDD patients suggests the abnormalities
      previously reported for adults may develop later in life as a result of neural
      cell loss.

PMID- 19108660
TI  - Neuroanatomic comparison of bipolar adolescents with and without cannabis use
      disorders.
AB  - OBJECTIVE: Co-occurrence of substance use and bipolar disorders is both common
      and associated with poor treatment response and greater functional impairment
      than either disorder alone. The neurophysiological correlates of this co
      morbidity however, remain unclear. In this pilot study, we compared brain
      morphometry between bipolar adolescents with co-occurring cannabis use disorders
      (CUD) and bipolar adolescents without any substance use disorder. METHODS: Whole
      brain structural magnetic resonance imaging (MRI) scans were obtained from 14
      bipolar adolescents. Seven study participants were diagnosed with CUD before
      and/or shortly after their MR scan was obtained, and 7 subjects were free of any
      substance use disorder at the time of their MR scan as well as during
      longitudinal follow up. Morphologic differences were calculated using voxel-based
      morphometry implemented using statistical parametric mapping software (SPM2).
      RESULTS: Bipolar adolescents with co-occurring CUD demonstrated decreased gray
      matter volume (GMV) in the left fusiform gyrus and increased GMV in the right
      caudate and precentral gyrus, as well as increased gray matter density in the
      right middle occipital and fusiform gyri and cerebellar vermis. CONCLUSIONS:
      Bipolar adolescents with CUD demonstrate evidence of greater structural
      abnormalities than adolescents with bipolar disorder alone in frontal and
      temporal cortical regions, as well as in subcortical areas linked with emotion
      and motivational regulation. Although the limited prescan exposure to marijuana
      in these adolescents tentatively suggests that these findings may reflect
      underlying differences, the direct effect of cannabis exposure may also be
      involved.

PMID- 19108661
TI  - A review of co-morbid depression in pediatric ADHD: etiology, phenomenology, and
      treatment.
AB  - This paper reviews the literature and highlights the need for further research
      regarding the phenomenology, etiology, assessment, and treatment of co-morbid
      depression in patients with attention-deficit/hyperactivity disorders (ADHD).
      Depression occurs in youths with ADHD at a significantly higher rate than in
      youths without ADHD. Youths with ADHD and depression together have a more severe
      course of psychopathology and a higher risk of long-term impairment and suicide
      than youths with either disorder alone. Assessment of such co-morbid depression
      is complicated by overlapping symptoms with ADHD and with other disorders that
      commonly occur with ADHD. Depressive disorders typically emerge several years
      after the onset of ADHD and may arise from environmental difficulties associated
      with chronic ADHD that interact with genetic risks as the child gets older.
      Despite a scarcity of well-designed treatment studies for youths with ADHD and co
      morbid depression, there is increasing preliminary evidence for the role of
      stimulants, selective serotonergic reuptake inhibitors, bupropion, and
      atomoxetine to target either or both disorders. There is also some indirect
      evidence for the benefit of combining pharmacological treatments with
      psychosocial interventions that specifically target relevant environmental
      factors and functional impairments.

PMID- 19108663
TI  - Temperament in child offspring of parents with bipolar disorder.
AB  - OBJECTIVE: The aim of this study was to examine the relationship between
      temperament and psychopathology in child offspring of parents with bipolar
      disorder. METHOD: The Dimensions of Temperament-Revised (DOTS-R) and the
      Washington University in St. Louis Kiddie Schedule for Affective Disorders and
      Schizophrenia (WASH U K-SADS) were used to assess temperament and
      psychopathology, respectively in offspring (8-18 years) of parents with bipolar I
      disorder (OBP, n = 31) and demographically similar healthy offspring of parents
      without any Diagnostic and Statistical Manual of Mental Disorders, 4(th) edition
      (DSM-IV) diagnosis (OHC, n = 21). RESULTS: Compared to OHC, OBP had increased
      Activity Level-General scores (effect size, d = -0.78), and a trend for decreased
      Task Orientation (d = -0.78). OBP with mood disorders had trends for decreased
      Approach (d = 0.89), Flexibility-Rigidity (d = 1.01), Rhythmicity-Sleep (d =
      0.79), and Task Orientation (d = 0.89) as compared to OBP without mood disorders.
      OBP with attention-deficit/hyperactivity disorder (ADHD) showed a trend for
      decreased Task Orientation scores compared with those without ADHD (d = 0.82).
      CONCLUSION: Although limited by parent report, specific temperaments may be
      important in characterizing offspring of parents with bipolar disorder.
      Longitudinal studies to determine if certain temperaments inform treatment
      response and prognosis in this population are needed.

PMID- 19108662
TI  - The efficacy and tolerability of methylphenidate and behavior modification in
      children with attention-deficit/hyperactivity disorder and severe mood
      dysregulation.
AB  - OBJECTIVES: This study examines the tolerability and efficacy of methylphenidate
      (MPH) and behavior modification therapy (BMOD) in children with attention
      deficity/hyperactivity disorder (ADHD) and severe mood dysregulation (SMD).
      METHODS: Children (ages 5-12) from a summer program for ADHD were screened for
      SMD and additional manic-like symptoms using structured assessments and direct
      clinical interview with the Young Mania Rating Scale (YMRS). The SMD group was
      comprised of 33 subjects with SMD and elevated YMRS scores (mean = 23.7). They
      underwent weekly mood assessments plus the daily ADHD measures that are part of
      the program. The comparison group (n = 68) was comprised of the rest of the
      program participants. Using a crossover design, all subjects in both groups were
      treated with three varying intensities of BMOD (no, low, high) each lasting 3
      weeks, with MPH dose (placebo, 0.15 mg/kg t.i.d., 0.3mg/kg t.i.d., and 0.6 mg/kg
      t.i.d.) varying daily within each behavioral treatment. RESULTS: Groups had
      comparable ADHD symptoms at baseline, with the SMD group manifesting more
      oppositional defiant disorder/conduct disorder (ODD/CD) symptoms (p < 0.001).
      Both groups showed robust improvement in externalizing symptoms (p < 0.001).
      There was no evidence of differential treatment efficacy or tolerability.
      Treatment produced a 34% reduction in YMRS ratings in SMD subjects (p - 0.001).
      However, they still exhibited elevated YMRS ratings, more ODD/CD symptoms (p <
      0.001), and were more likely to remain significantly impaired at home than non
      SMD subjects (p < 0.05). CONCLUSIONS: MPH and BMOD are tolerable and effective
      treatments for children with ADHD and SMD, but additional treatments may be
      needed to optimize their functioning.

PMID- 19108664
TI  - A quantitative and qualitative review of neurocognitive performance in pediatric
      bipolar disorder.
AB  - Bipolar disorder (BD) is an increasingly prevalent diagnosis in youth. As a
      result, there has been a corresponding increase in interest about
      neuropsychological and cognitive profiles in children and adolescents diagnosed
      with BD. Meta-analysis of the existing literature comparing individuals with BD
      to healthy controls indicated that the largest differences are observed for
      measures of verbal memory (d = 0.77). Moderate differences were found in the
      areas of attention (d = 0.62), executive functioning (d = 0.62), working memory
      (d = 0.60), visual memory (d = 0.51), visual perceptual skills (d = 0.48), and
      verbal fluency (d = 0.45). Small differences were found for measures of reading
      (d = 0.40), motor speed (d = 0.33), and full-scale intelligence quotient (IQ) (d
      = 0.32). Often, few studies have provided relevant information for a particular
      neurocognitive domain. Despite this, several domains displayed heterogeneity of
      effect sizes across studies. Methodological factors explained the variance in
      effect sizes to different extents depending upon the cognitive domain. The
      changing influence of method artifacts is likely due to variable coverage of
      cognitive domains across studies and the use of different measures across
      studies. Findings are consistent with previous meta-analyses of the adult BD
      neurocognitive literature, suggesting that many of the deficits observed in
      adults are present earlier in the course of the illness. Study reporting
      guidelines are offered that may help clarify the impact of illness definitions,
      mood state, medication status, and other methodological variables on
      neurocognition in pediatric BD.

PMID- 19108665
TI  - Electroencephalographic sleep and hypothalamic-pituitary-adrenal changes from
      episode to recovery in depressed adolescents.
AB  - OBJECTIVE: The study examined electroencephalographic (EEG) sleep and
      hypothalamic-pituitary-adrenal (HPA) changes associated with depressive episode
      and during recovery in adolescent depression. METHODS: Sixteen adolescents with
      major depressive disorder and 16 volunteers with no personal or family history of
      psychiatric disorder participated in a three-night EEG sleep protocol along with
      nocturnal urinary free cortisol (NUFC). Depressed subjects also were restudied
      during stable remission from the depressive episode. RESULTS: Compared with
      controls, depressed adolescents had significantly reduced sleep efficiency,
      shorter latency to rapid eye movement (REM) sleep, increased phasic REM sleep,
      and elevated NUFC excretion. Among depressed subjects, EEG sleep values did not
      change significantly from episode to remission. NUFC excretion reduced
      significantly during remission from the depressive episode. CONCLUSIONS: The
      findings that EEG sleep measures are independent of clinical state, whereas HPA
      variables are state dependent, suggest that sleep and HPA measures make a
      differential contribution to our understanding of the pathophysiology and
      prognosis of mood disorders in adolescent patients.

PMID- 19108666
TI  - A pilot pharmacotherapy trial for depressed youths at high genetic risk for
      bipolarity.
AB  - Children and adolescents who are the offspring of a bipolar parent and who first
      present with major depressive disorder (MDD) are at high risk for eventually
      developing bipolar disorder. In this report, the authors describe a group of 9
      such high-risk children and adolescents with MDD, aged 7-16 years, who were
      randomized to receive treatment with either paroxetine monotherapy or combination
      paroxetine-divalproex sodium therapy. In the long-term management of depressive
      symptomatology in these patients, neither treatment appeared to be particularly
      effective. As a result, future treatment studies in this population appear to be
      warranted, not only due to the putative impending risk of developing bipolar
      disorder, but also the manifest risk of current depressive episodes.

PMID- 19108667
TI  - Neurochemical alterations in adolescent bipolar depression: a proton magnetic
      resonance spectroscopy pilot study of the prefrontal cortex.
AB  - OBJECTIVE: Identifying neurochemical alterations in adolescent bipolar depression
      may enhance our understanding of the neurophysiology of bipolar disorder across
      the age spectrum. The objective of this study was to compare in vivo
      neurometabolite concentrations in bipolar adolescents with a depressed episode
      and healthy adolescents using proton magnetic resonance spectroscopy ((1)H MRS).
      METHOD: Bipolar adolescents with a depressed episode (n = 28) and healthy
      adolescents (n = 10) underwent a (1)H MRS scan. Anterior cingulate (ACC) and left
      and right ventral lateral prefrontal (LVLPFC, RVLPFC) metabolite concentrations
      were calculated and compared between groups using analysis of covariance
      (ANCOVA). RESULTS: ANCOVA showed significant group differences in ACC N-acetyl
      aspartate (NAA) (F(1,33) = 17.8, p = 0.0002), LVLPFC choline (Cho) (F(1,32) =
      13.1, p = 0.001), creatine/phosphocreatine (Cr) (F(1,32) = 18.5, p = 0.0002), and
      NAA (F(1,32) = 13.6, p = 0.0008), and RVLPFC Cr (F(1,32) = 9.6, p = 0.004), mI
      (F(1,32) = 11.1, p = 0.002), and NAA (F(1,32) = 11.4, p = 0.002) concentrations.
      In general, the bipolar depressed group had higher neurometabolite concentrations
      than the healthy group. CONCLUSIONS: There may be localized alterations in brain
      neurometabolites in adolescents with bipolar depression. Limitations include lack
      of bipolar adolescents in other mood states and potential confounding effects of
      prior psychotropic medication use. Confirmatory (1)H MRS studies in larger
      samples of youths with bipolar depression are needed.

PMID- 19108670
TI  - Postraumatic stress disorder and reactive attachment disorder: outcome in an
      adolescent.

PMID- 19108672
TI  - Efficient method for the synthesis of 2,3-unsubstituted nitro containing indoles
      from o-fluoronitrobenzenes.
AB  - A methodology was developed for the efficient synthesis of 2,3-unsubstituted
      nitro containing indoles via acid catalyzed intramolecular electrophilic
      cyclization. Subsequent reduction of nitro groups allows the construction of some
      indole fused heterocycles and indole quinone diimines. This strategy provides an
      efficient method for the preparation of biologically and medicinally interesting
      molecules.

PMID- 19108673
TI  - Highly cis-selective cyclopropanations with ethyl diazoacetate using a novel
      Rh(I) catalyst with a chelating N-heterocyclic iminocarbene ligand.
AB  - A structurally characterized Rh(I) iminocarbene complex (N,C)Rh(CO)Cl is
      activated with AgOTf to act as a highly cis-selective catalyst for the
      cyclopropanation of substituted styrenes and other alkenes with ethyl
      diazoacetate (11 examples, 10-99% yield, up to >99% cis-selectivity).

PMID- 19108674
TI  - Nickel-catalyzed oxidative coupling reactions of two different terminal alkynes
      using O(2) as the oxidant at room temperature: facile syntheses of unsymmetric
      1,3-diynes.
AB  - Two different terminal alkynes now can be coupled together in the presence of
      NiCl(2).6H(2)O/CuI by using an excess of one of the terminal alkyne substrates.
      The new method employed 20 mol % TMEDA as the ligand and environmentally benign
      O(2) or air as the oxidant. It is the first example using Ni-salt as catalyst by
      employing air or O(2) as oxidant, which led to efficient heterocoupling of two
      different alkynes.

PMID- 19108675
TI  - Impact of endothelial cells and mechanical conditioning on smooth muscle cell
      extracellular matrix production and differentiation.
AB  - The aim of the current study was to explore the separate and coupled effects of
      endothelial cell (EC) presence and mechanical conditioning on smooth muscle cell
      (SMC) responses by combining bilayered poly(ethylene glycol) diacrylate (PEGDA)
      hydrogels with a pulsatile flow bioreactor. Each construct was composed of an
      outer PEGDA layer containing SMC and an inner PEGDA layer, either with or without
      EC. After an initial 3 days of static culture, EC(+) and EC(-) constructs were
      each further divided into two subgroups, half of which received mechanical
      conditioning mimetic of late gestation (mean pressures of approximately 50 mmHg
      and peak-to-trough pressure differentials of approximately 20 mmHg at
      approximately 140-180 beats/min) and half of which were cultured statically.
      After 18 additional days of culture, the SMC-containing layer of each construct
      was harvested, and western blots and quantitative histology were conducted to
      compare collagen type I, collagen type III, and elastin levels among treatment
      groups. SMC differentiation was evaluated by focusing on SMC marker calponin h1
      and direct regulators of its gene expression-the transcription factor serum
      response factor (SRF) and two of its binding partners, myocardin and Elk-1.
      Combined EC and pulsatile flow conditioning increased elastin production, but
      decreased collagen type I deposition. Further, combined EC presence and
      mechanical stimulation increased SRF levels and the ratio of myocardin to active,
      phosphorylated Elk-1. This modulation of SRF and its binding partners appeared to
      result in a net increase in SMC differentiation, as evidenced by an associated
      increase in calponin h1 levels.

PMID- 19108676
TI  - A poly(lactic acid-co-caprolactone)-collagen hybrid for tissue engineering
      applications.
AB  - A biodegradable hybrid scaffold consisting of a synthetic polymer, poly(lactic
      acid-co-caprolactone) (PLACL), and a naturally derived polymer, collagen, was
      constructed by plastic compressing hyperhydrated collagen gels onto a flat warp
      knitted PLACL mesh. The collagen compaction process was characterized, and it was
      found that the duration, rather than the applied load under the test conditions
      in the plastic compression, was the determining factor of the collagen and cell
      density in the cell-carrying component. Cells were spatially distributed in three
      different setups and statically cultured for a period of 7 days. Short-term
      biocompatibility of the hybrid construct was quantitatively assessed with
      AlamarBlue and qualitatively with fluorescence staining and confocal microscopy.
      No significant cell death was observed after the plastic compression of the
      interstitial equivalents, confirming previous reports of good cell viability
      retention. The interstitial, epithelial, and composite tissue equivalents showed
      no macroscopic signs of contraction and good cell proliferation with a two- to
      threefold increase in cell number over 7 days. Quantitative analysis showed a
      homogenous cell distribution and good biocompatibility. The results indicate that
      viable and proliferating multilayered tissue equivalents can be engineered using
      the PLACL-collagen hybrid construct in the space of several hours.

PMID- 19108677
TI  - Isolation and characterization of adult human liver progenitors from ischemic
      liver tissue derived from therapeutic hepatectomies.
AB  - Recent evidence suggests that progenitor cells in adult tissues and embryonic
      stem cells share a high resistance to hypoxia and ischemic stress. To study the
      ischemic resistance of adult liver progenitors, we characterized remaining viable
      cells in human liver tissue after cold ischemic treatment for 24-168 h, applied
      to the tissue before cell isolation. In vitro cultures of isolated cells showed a
      rapid decline of the number of different cell types with increasing ischemia
      length. After all ischemic periods, liver progenitor-like cells could be
      observed. The comparably small cells exhibited a low cytoplasm-to-nucleus ratio,
      formed densely packed colonies, and showed a hepatobiliary marker profile. The
      cells expressed epithelial cell adhesion molecule, epithelial-specific (CK8/18)
      and biliary-specific (CK7/19) cytokeratins, albumin, alpha-1-antitrypsin,
      cytochrome-P450 enzymes, as well as weak levels of hepatocyte nuclear factor-4
      and gamma-glutamyl transferase, but not alpha-fetoprotein or Thy-1. In vitro
      survival and expansion was facilitated by coculture with mouse embryonic
      fibroblasts. Hepatic progenitor-like cells exhibit a high resistance to ischemic
      stress and can be isolated from human liver tissue after up to 7 days of
      ischemia. Ischemic liver tissue from various sources, thought to be unsuitable
      for cell isolation, may be considered as a prospective source of hepatic
      progenitor cells.

PMID- 19108679
TI  - In vivo recruitment of hematopoietic cells using stromal cell-derived factor 1
      alpha-loaded heparinized three-dimensional collagen scaffolds.
AB  - Implantable three-dimensional (3D) constructs to engineer tissue have great
      therapeutic potential in regenerative medicine and immunotherapy. However,
      autonomous recruitment of cells into the engineered scaffold in vivo is hampered
      by lack of attracting scaffolds. As a first step to engineering immune tissue, 3D
      collagen scaffolds were investigated for their ability to enhance in vivo
      recruitment and growth of various hematopoietic cells. Scaffolds containing
      immobilized heparin to trap the stem cell chemo-attractant stromal cell-derived
      factor 1 alpha (SDF1alpha) were implanted subcutaneously into C57Bl6 mice, and
      influx of cells was monitored using immunohistochemistry. Five weeks post
      implantation, heparinized scaffolds were always populated by cells, but
      incorporating SDF1alpha considerably stimulated recruitment of cells. SDF1alpha
      could not exert this effect when the formation of a SDF1alpha gradient was
      abrogated. Scaffolds were mainly populated by CD11b+ and CD11c+ myeloid cells and
      fibroblasts. One week after implantation, scaffolds harbored only low numbers of
      cells. Apparently, not all CXCR4-expressing cells, like large numbers of
      granulocytes, migrate into the scaffold, but retransplantation of a 1-week-old
      scaffold from a CD45.2(+) into a CD45.1(+) mouse yielded a scaffold harboring
      mainly CD45.2(+) cells after 5 weeks. These data confirm that only a few
      progenitor cells are recruited early after implantation. These cells then
      proliferate and differentiate along different lineages and determine the outcome
      after 5 weeks.

PMID- 19108680
TI  - Fabrication of the microgrooved/microporous polylactide substrates as peripheral
      nerve conduits and in vivo evaluation.
AB  - An innovative technique combining phase transition and microprinting in one step
      was applied to fabricate the nerve conduits used in peripheral nerve
      regeneration. The asymmetric microporosity served to generate asymmetric
      permeability, and the surface microgrooves were introduced to achieve cell
      alignment in vitro. The symmetric/asymmetric porous poly(D,L-lactide) (PLA)
      substrates with microgrooves on the surface were tested for their ability to
      repair 10 mm sciatic nerve transection defects in rats. The in vivo results
      showed that porous PLA conduits maintained a stable supporting structure during
      the entire regeneration process. The myelin sheaths of the regenerated nerve in
      asymmetric conduits were thicker than in symmetric groups at 4 weeks. Moreover,
      the regenerated nerves in the asymmetric conduits with surface microgrooves had
      the highest degree of myelination at 4 weeks and the most number of vessels at 6
      weeks. The walking track analysis also implied that the asymmetric conduits with
      surface microgrooves had the highest degree of functional recovery. Based on the
      study, the combination of microgrooves and asymmetric microporous structure could
      be employed in the design of nerve conduits for peripheral nerve regeneration in
      the future.

PMID- 19108681
TI  - Novel isolation and biochemical characterization of immortalized fibroblasts for
      tissue engineering vocal fold lamina propria.
AB  - Tissue regeneration of the vocal fold lamina propria extracellular matrix (ECM)
      will be facilitated by the use of suitable vocal fold fibroblast (VFF) cell lines
      in appropriate model systems. Primary human VFFs (hVFFs) were steadily transduced
      by a retroviral vector containing human telomerase reverse transcriptase (hTERT)
      gene; immortalized cells grew and divided vigorously for more than 120 days.
      Biochemical characterization of the six transduced lines included, at different
      time points, expression of hTERT, telomerase activity, telomere lengths, and
      transcript levels of ECM constituents. Telomere lengths of the transfected lines
      were elongated and stable. Gene expression levels of collagen Ialpha1, collagen
      Ialpha2, collagen VIalpha3, elastin, and fibronectin were measured between the
      transduced cell clones and the primary hVFFs to verify transcription. Absence of
      inter- and intraspecies contamination was confirmed with DNA fingerprinting and
      karyotype analysis. Cell morphology, growth, and transcription expression were
      examined on 2D scaffolds-collagen, fibronectin, and hyaluronic acid. Immortalized
      hVFFs demonstrated normal attachment and spread on 2D scaffolds. Collagen
      Ialpha1, collagen Ialpha2, collagen VIalpha3, elastin, and fibronectin transcript
      expression was measured from immortalized hVFFs, for all surfaces. This is the
      first report of immortalization and biochemical characterization of hVFFs,
      providing a novel and invaluable tool for tissue regeneration applications in the
      larynx.

PMID- 19108682
TI  - Scanning electron microscopy and energy-dispersive x-ray microanalysis: a
      valuable tool for studying cell surface antigen expression on tissue-engineered
      scaffolds.
AB  - The influence of an acellular porcine matrix on proinflammatory activation of
      endothelial cells (EC) during normoxia and hypoxia was investigated by a newly
      established semi-quantitative electron microscopic procedure. As a model, three
      adhesion molecules (E-selectin, ICAM-1, and VCAM-1) were localized by silver
      enhanced immunogold staining and energy dispersive X-ray microanalysis after
      normoxic or hypoxic pretreatment of the cells and subsequent stimulation with IL
      1beta. Morphology of EC grown on porcine matrix or coverslips was recorded
      simultaneously using secondary electron imaging. EC appeared tightly attached to
      the underlying surfaces with their typical cobblestone-like morphology.
      Statistically significant upregulations upon stimulation with IL-1beta were
      observed in both groups for all three adhesion molecules. Hypoxic pretreatment of
      the specimens with subsequent reoxygenation neither induced morphological changes
      nor caused an upregulation of adhesion molecule expression in cells grown on
      acellular porcine tissue. Unexpectedly, in cells seeded onto the acellular
      matrix, IL-1beta failed to upregulate ICAM-1 expression after a short period of
      hypoxia. The surface expression of VCAM-1 was also significantly lower even under
      normoxic conditions, which might indicate the development of functional
      impairment of cells in contact with acellular porcine tissue. The method
      presented in this study has proven valuable for the determination of antigen
      expression on scaffold materials in parallel with the characterization of surface
      morphology.

PMID- 19108683
TI  - Supercritical processing as a route to high internal surface areas and permanent
      microporosity in metal-organic framework materials.
AB  - Careful processing of four representative metal-organic framework (MOF) materials
      with liquid and supercritical carbon dioxide (ScD) leads to substantial, or in
      some cases spectacular (up to 1200%), increases in gas-accessible surface area.
      Maximization of surface area is key to the optimization of MOFs for many
      potential applications. Preliminary evidence points to inhibition of mesopore
      collapse, and therefore micropore accessibility, as the basis for the
      extraordinarily efficacious outcome of ScD-based activation.

PMID- 19108684
TI  - ACE variants interact with the RAS pathway to confer risk and protection against
      type 2 diabetic nephropathy.
AB  - Genetic predisposition has been proposed to be a major determinant in the
      development of renal complications of diabetes. Among candidate genes examined
      for susceptibility to diabetic nephropathy, angiotensin-converting enzyme (ACE)
      gene has been found to be associated with pathogenesis and progression of
      diabetic nephropathy. However, the role of other renin-angiotensin system (RAS)
      polymorphisms and their possible interactions with different ACE I/D genotypes
      are less clearly defined. Recent studies also show that ACE haplotypes may be
      better predictors to disease susceptibility. Thus, in the present study, we
      evaluated the association of ACE haplotypes and the interactions of ACE,
      angiotensinogen (AGT), and angiotensin II receptor type I (AGTR1) gene
      polymorphisms with DNP in Asian Indians. We genotyped seven variants of the RAS
      pathway genes (ACE, AGT, and AGTR1) in type 2 diabetic cohorts without
      nephropathy (DM) and with nephropathy (DNP), using allele-specific
      oligonucleotide-PCR, and PCR-restriction fragment length polymorphism assays. We
      studied the interaction of these variants with each other and ACE I/D
      polymorphism. Frequency of ACE D allele and DD genotype (ACE I/D) was
      significantly higher in DNP (p < 0.005) and was associated with increased risk of
      nephropathy. The frequency of T allele, MT/TT genotypes (AGT: M235T), and C
      allele 1166CC genotype (AGTR1: A1166C) was higher and associated with increased
      risk of DNP (235T, p < 0.0001; 235TT/MT, p < 0.01; 1166C, p < 0.007; 1166CC, p <
      0.0001). The ACE locus revealed a near doubling in the prevalence of T-D-G risk
      haplotype (odds ratio, 1.76) in DNP (0.13) compared to DM (0.08; p < 0.02). ACE
      haplotypes carrying the I allele were associated with a lower risk of DNP (C-I-A,
      p < 0.04; C-I-G, p < 0.008). ACE ID/DD genotypes in combination with ACE rs4311,
      rs4343, and AGT rs699 mutant genotypes increased the risk of DNP development
      fourfold (p < 0.01). This study provides the first evidence for a disease
      haplotype for DNP at the ACE locus in Asian Indians. The study further indicates
      that ACE D allele individually and in interaction with other RAS single
      nucleotide polymorphisms significantly increases the risk of nephropathy in type
      2 diabetic patients of Asian Indian origin.

PMID- 19108685
TI  - Activating Pd by morphology tailoring for oxygen reduction.
AB  - Pd has been the focus of recent research for Pt-alternative catalysts for the
      oxygen reduction reaction (ORR). It has been found that upon appropriate
      modification of its electronic structure, the catalytic activity of Pd can become
      comparable to that of Pt. However, the structure-activity relationships of Pd
      catalysts have hitherto not been well studied or understood. In the present work,
      we report a new finding that there is a strong dependence of the activity of Pd
      toward the ORR on its morphology. By simply adjusting the precursor concentration
      in the electrochemical deposition of Pd, we are able to tailor the morphology of
      the deposited Pd from nanoparticles to nanorods. Surprisingly, the surface
      specific activity of Pd nanorods (Pd-NRs) toward the ORR was found to be not only
      10-fold higher than that of Pd nanoparticles (Pd-NPs), the conventional shape of
      electrocatalysts, but also comparable to that of Pt at operating potentials of
      fuel cell cathodes. The morphology-activity relationships of Pd-NRs were further
      studied through a combination of electrochemical experiments and density
      functional theory (DFT) calculations. As revealed by its characteristic profile
      for CO stripping, the morphology of Pd-NRs features the exposure of Pd(110)
      facets, which exhibit superior ORR activity. The underlying mechanism, indicated
      by DFT calculations, could be ascribed to the exceptionally weak interaction
      between an O adatom and a Pd(110) facet. This finding furthers our understanding
      of Pd catalysis and casts a new light on the relevant catalyst design criteria.

PMID- 19108686
TI  - Kinetic study of the antioxidant activity of pyrroloquinolinequinol (PQQH(2), a
      reduced form of pyrroloquinolinequinone) in micellar solution.
AB  - Kinetic study of the aroxyl radical-scavenging action of pyrroloquinolinequinol
      [PQQH(2), a reduced form of pyrroloquinolinequinone (PQQ)] and water-soluble
      antioxidants (vitamin C, cysteine, glutathione, and uric acid) has been
      performed. The second-order rate constants (k(s)) for the reaction of aroxyl
      radical with PQQH(2) and water-soluble antioxidants were measured in Triton X-100
      micellar solution (5.0 wt %) (pH 7.4), using stopped-flow and UV-visible
      spectrophotometers. The k(s) values decreased in the order PQQH(2) > vitamin C >>
      cysteine > uric acid > glutathione. The aroxyl radical-scavenging activity of
      PQQH(2) was 7.4 times higher than that of vitamin C, which is well-known as the
      most active water-soluble antioxidant. Furthermore, PQQNa(2) (disodium salt of
      PQQ) was easily reduced to PQQH(2) by reaction of PQQNa(2) with glutathione and
      cysteine in buffer solution (pH 7.4) under nitrogen atmosphere. The result
      suggests that PQQ exists as a reduced form throughout the cell and plays a role
      as antioxidant.

PMID- 19108687
TI  - Cranberry phytochemical extract inhibits SGC-7901 cell growth and human tumor
      xenografts in Balb/c nu/nu mice.
AB  - Cranberry extract possesses potent antioxidant capacity and antiproliferative
      activity against cancer in vitro and in vivo. The objectives of this study were
      to determine whether the cranberry extract inhibited proliferation of human
      gastric cancer SGC-7901 cells and human gastric tumor xenografts in the Balb/c
      nu/nu mouse. Cranberry extract at doses of 0, 5, 10, 20, and 40 mg/mL
      significantly inhibited proliferation of SGC-7901 cells, and this suppression was
      partly attributed to decreased PCNA expression and apoptosis induction. In a
      human tumor xenograft model, the time of human gastric tumor xenografts in the
      mouse was delayed in a dose-dependent manner. A dose-response inhibition was also
      observed in the averages of size, weight, and volume of tumor xenografts in the
      mouse between the control and cranberry-treated groups. These results demonstrate
      fresh cranberries to be a chemopreventive reagent.

PMID- 19108689
TI  - Non-B HIV type 1 subtypes among men who have sex with men in Rome, Italy.
AB  - An increase in the circulation of HIV-1 non-B subtypes has been observed in
      recent years in Western European countries. Due to the lack of data on the
      circulation of HIV-1 non-B subtypes among European HIV-1-infected men who have
      sex with men (MSM), a biomolecular study was conducted in Rome, Italy. HIV-1
      partial pol gene sequences from 111 MSM individuals (76 drug naive and 35 drug
      experienced) were collected during the years 2004-2006. All these sequences were
      analyzed using the REGA HIV-1 Subtyping Tool, and aligned using CLUSTAL X
      followed by manual editing using the Bioedit software. A BLAST search for non-B
      subtype sequences was also performed. Twenty-six (23.4%) MSM were not Italians.
      Eight individuals (7.2%) were diagnosed as HIV infected before 1991, 20 (18.0%)
      between 1991 and 1999, and 83 (74.8%) from 2000 to 2006. Fifteen (15/111, 13.5%)
      individuals were infected with the non-B subtype. The percentage of infection
      with HIV-1 non-B subtypes was 8.2% (7/85) among Italian MSM and 30.8% (8/26)
      among the non-Italians (OR = 4.95 95% IC: 1.40-17.87). Individuals infected with
      the non-B subtype were significantly younger than those infected with the HIV-1 B
      subtype (28 years vs. 34 years, p = 0.003). The CRFs were more prevalent (8.1%)
      than pure subtypes (5.4%), which were distributed as follows: subtype C (2.6%),
      subtype A1 (1.7%), and subtype F1 (0.9%). Major mutations conferring resistance
      to antiretroviral drugs (ARV) were not found among HIV-1 non-B subtype drug-naive
      patients but were found in two ARV-experienced individuals. The data show that
      viral diversity is likely increasing in a population group that had been
      previously characterized by the circulation of HIV-1 subtype B.

PMID- 19108690
TI  - High frequency of vitamin D deficiency in ambulatory HIV-Positive patients.
AB  - Several reports have suggested an increased prevalence of osteopenia and
      osteoporosis in HIV-infected individuals. Vitamin D deficiency may be a risk
      factor for osteoporosis and bone fractures. We aimed to determine the prevalence
      of vitamin D insufficiency in an outpatient HIV clinic in Boston. We collected
      serum levels of 25-OH vitamin D and evaluated calcium and vitamin D intake in
      adult HIV-positive outpatients during the winter and spring of 2005. Fifty-seven
      subjects were enrolled. The prevalence of moderate (< or = 20 and>10 ng/ml) and
      severe (< or =10 ng/ml) 25-OH vitamin D deficiency was 36.8% and 10.5%,
      respectively. Lower vitamin D intake was significantly associated with severe 25
      OH vitamin D deficiency (p=0.01). Lactose intolerance tended to be associated
      with severe vitamin D deficiency (p=0.08). Antiretroviral use and low daily
      calcium intake were significantly associated with elevated parathyroid hormone
      levels (p=0.01 and 0.03, respectively). Vitamin D deficiency was frequent in
      ambulatory HIV-positive patients. HIV-infected individuals living in areas with
      low exposure to ultraviolet light during winter may benefit from vitamin D
      supplementation.

PMID- 19108688
TI  - Changes in the HIV type 1 envelope gene from non-subtype B HIV type 1-infected
      children in Kenya.
AB  - A switch of coreceptor usage from CCR5 to CXCR4 occurs in about half of HIV-1
      infected individuals in the natural course of infection. To investigate whether
      antiretroviral therapy (ART) enhances the coreceptor switch of HIV-1, we
      genotypically analyzed the env-V3 amino acid sequences from 81 HIV-1-infected
      children in Kenya whose plasma samples were obtained between 2000 and 2007. Of 41
      children on ART, 35 had HIV-1 using CCR5 as a coreceptor at baseline. In 7 (20%)
      of them HIV-1 switched the coreceptor usage during the follow-up period. The mean
      duration of ART to the time of coreceptor switch was 2.6 years (range: 0.5-5.2).
      Of the remaining 40 children without ART, 32 had HIV-1 using CCR5 as a coreceptor
      at baseline and in 3 (9.4%) HIV-1 switched the coreceptor usage. The mean age of
      the children with HIV-1 coreceptor switch with and without ART was 7.3 and 9.7
      years, respectively. The difference in the rate and age of coreceptor switch
      between treated and untreated children was not significant (p = 0.38 and 0.31,
      respectively). Of the HIV-1-infected children, 10 started ART by the age of 5
      years (rapid progressors) and 23 did not need ART by the age of 10 years (slow
      progressors). The rate of coreceptor switch was strongly higher in rapid
      progressors (40%) than slow progressors (8.7%) (p = 0.053). These results suggest
      that switching of coreceptor usage from CCR5 to CXCR4 among HIV-1-infected
      children is not influenced by ART, but by factors responsible for rapid disease
      progression.

PMID- 19108691
TI  - Recreational drug use and risk of Kaposi's sarcoma in HIV- and HHV-8-coinfected
      homosexual men.
AB  - Experimental data suggested that exposure to recreational drugs might adversely
      affect antitumor immunity, which led us to examine the hypothesis that use of
      marijuana, cocaine, poppers, and amphetamines might increase the risk of Kaposi's
      sarcoma (KS) in HIV- and HHV-8-coinfected homosexual men. We analyzed data
      prospectively collected from the Multicenter AIDS Cohort Study (MACS) between
      1984 and 2002. Among the 1335 HIV- and HHV-8-coinfected white men, 401 KS cases
      were identified. Multivariable Cox regression models were used to estimate the
      effects of time-varying recreational drug use on KS risk adjusting for potential
      confounders. The effects of both recent use (6 months prior) of recreational
      drugs and lagged exposure (i.e., use from 3 and 5 years prior) were examined. We
      did not observe any clear association with KS for recent use of any of the four
      drugs. In the analyses using lagged exposures, KS risk was associated with use of
      poppers 3-5 years prior [hazard ratio (HR)(3 years prior) = 1.27, 95% CI (0.97
      1.67), HR(5 years prior) = 1.46 (1.01-2.13)]. However, no clear dose-response
      relationship was observed. These findings do not support a biological association
      between use of these substances and KS development in HIV- and HHV-8-coinfected
      homosexual men.

PMID- 19108692
TI  - Cervical HIV-specific IgA in a population of commercial sex workers correlates
      with repeated exposure but not resistance to HIV.
AB  - We conducted a comprehensive cross-sectional analysis of total and HIV-specific
      cervical antibody levels in HIV-1-resistant, uninfected, and infected women in
      order to examine the role of HIV-specific antibody responses in the female
      genital tract and examine the effect on antibody levels of various epidemiologic
      factors in this population. Cervical lavages were collected from 272 subjects of
      the Pumwani commercial sex worker cohort. Total and HIV-specific genital tract
      IgA and IgG levels were measured using an ELISA and correlated with behavioral
      and demographic factors. No significant difference was seen between cervical HIV
      specific IgA levels in infected, uninfected, and resistant individuals, nor were
      any correlations between cervical HIV-specific IgA and neutralization capacity or
      viral shedding seen. We did, however, note increased HIV-specific IgA in HIV
      negative women with four or more clients per day, and decreased HIV-specific IgA
      in both long-term nonprogressors and long-term survivors. These results show that
      there is not a strong cohort-wide correlation between HIV-specific cervical IgA
      levels and resistance to infection by HIV-1 as previously believed, but there is
      a correlation between exposure to HIV and HIV-specific cervical IgA. Our findings
      do not preclude the possibility that functional differences in the cervical IgA
      of HEPS women may play a role in resistance, but argue that HIV-specific
      responses may not be a universal protective factor. They also indicate that
      resistance to HIV is a complex condition related to more factors than exposure.
      Further studies of correlates of immune protection in these individuals would be
      beneficial to the field.

PMID- 19108694
TI  - Genotypic characterization of CRF01_AE env genes derived from human
      immunodeficiency virus type 1-infected patients residing in central Thailand.
AB  - CRF01_AE is a major subtype of human immunodeficiency virus type 1 (HIV-1)
      circulating in Southeast Asia, including Thailand. HIV-1 env genes were amplified
      by polymerase chain reaction from blood samples of HIV-1-infected patients
      residing in Thailand in 2006, and cloned into the pNL4-3-derived reporter viral
      construct. Generated envelope protein (Env)-recombinant virus was examined for
      its infectivity, and then 35 infectious CRF01_AE Env-recombinant viruses were
      selected. Sequencing analysis revealed that the interclone variation of the
      deduced amino acid sequences was higher in CRF01_AE env genes isolated in 2006
      than in those isolated in the early 1990s, suggesting that env gene variation has
      been increasing gradually among CRF01_AE viruses prevalent in Thailand. We also
      examined the characteristics of the deduced amino acid sequences of 35 CRF01_AE
      env genes. Our results may provide useful information to help in better
      understanding the genotype of env genes of CRF01_AE viruses currently circulating
      in Thailand.

PMID- 19108693
TI  - Safety and immunogenicity of adenovirus-vectored near-consensus HIV type 1 clade
      B gag vaccines in healthy adults.
AB  - Vaccines inducing pathogen-specific cell-mediated immunity are being developed
      using attenuated adenoviral (Ad) vectors. We report the results of two
      independent Phase I trials of similar replication-deficient Ad5 vaccines
      containing a near-consensus HIV-1 clade B gag transgene. Healthy HIV-uninfected
      adults were enrolled in two separate, multicenter, dose-escalating, blinded,
      placebo-controlled studies to assess the safety and immunogenicity of a three
      dose homologous regimen of Ad5 and MRKAd5 HIV-1 gag vaccines given on day 1, week
      4, and week 26. Adverse events were collected for 29 days following each
      intradeltoid injection. The primary immunogenicity endpoint was the proportion of
      subjects with a positive unfractionated Gag-specific IFN-gamma ELISPOT response
      measured 4 weeks after the last dose (week 30). Analyses were performed after
      combining data for each dose group from both protocols, stratifying by baseline
      Ad5 titers. Overall, 252 subjects were randomized to receive either vaccine or
      placebo, including 229 subjects (91%) who completed the study through week 30.
      Tolerability and immunogenicity did not appear to differ between the Ad5 and
      MRKAd5 vaccines. The frequency of injection-site reactions was dose dependent.
      Systemic adverse events were also dose dependent and more frequent in subjects
      with baseline Ad5 titers <200 versus > or =200, especially after the first dose.
      The percent of ELISPOT responders and the ELISPOT geometric means overall were
      significantly higher for all four vaccine doses studied compared to placebo, and
      were generally higher in vaccine recipients with baseline Ad5 titers <200 versus
      > or = 200. Ad5 titers increased after vaccination in a dose-dependent fashion.
      Both Ad5-vectored HIV-1 vaccines were generally well tolerated and induced cell
      mediated immune responses against HIV Gag-peptides in the majority of healthy
      adults with baseline Ad5 titers <200. Preexistent and/or vaccine-induced immunity
      to the Ad5 vector may dampen the CMI response to HIV Gag.

PMID- 19108695
TI  - A new 1'-methylenedisulfide deoxyribose that forms an efficient cross-link to DNA
      cytosine-5 methyltransferase (DNMT).
AB  - A newly designed 1'-methylenedisulfide deoxyribose probe can efficiently cross
      link to DNA cytosine-5-methyltransferases (DNMTs) through the active Cys residue,
      which provides a new tool to covalently trap DNMT-DNA complexes.

PMID- 19108696
TI  - 7-Azabicyclo[2.2.1]heptane as a unique and effective dialkylamino auxochrome
      moiety: demonstration in a fluorescent rhodamine dye.
AB  - A new type of a highly fluorescent sulforhodamine dye, 221SR, was designed and
      synthesized using 7-azabicylco[2.2.1]heptyl moieties as the electron donating
      auxochrome groups. Using the prototypical dye tetramethylsulforhodamine, TMSR, as
      a benchmark, we show this new dye has higher fluorescent quantum yields, Phi,
      (Phi = 0.95 vs Phi = 0.65 at 20 degrees C), emission efficiencies that are
      invariant in the 20--> 60 degrees C temperature range (Phi = 0.95 vs Phi = 0.38
      at 60 degrees C), and fluorescence lifetimes that increase with a rise in
      temperature (20 --> 60 degrees C) as compared to a decrease for the benchmark dye
      (3.8 --> 3.9 vs 2.8 --> 1.7 ns). Importantly, photostability studies found the
      azabicyclic rhodamine to be many times more stable than its tetramethyl analogue.
      To the best our knowledge this is the first report of the use of an apex-N
      substituted azabicycloalkane as an electron donor group in any class of donor
      acceptor dye. Thus, the concept of using an apex-substitutes bicyclic amine as a
      donor moiety constitutes a new paradigm for simultaneously inducing remarkable
      beneficial effects on both emission efficiency and photostability in a donor
      acceptor fluorophore.

PMID- 19108698
TI  - Stable scaffolds for reacting Si nanowires with further organic functionalities
      while preserving Si-C passivation of surface sites.
AB  - We report on Si NWs modified by covalent scaffolds, via SiC bonds, that give
      nearly full coverage of the Si atop sites and, at the same time, provide a route
      for subsequent functionalization. The obtained CH(3)CHCHSi NWs exhibit superior
      oxidation resistance over Si NWs that are modified with CH(3) or CH(3)CC
      functionalities, which give nearly full coverage of the Si atop site too.

PMID- 19108697
TI  - A general and efficient method for the site-specific dual-labeling of proteins
      for single molecule fluorescence resonance energy transfer.
AB  - A general strategy for the site-specific dual-labeling of proteins for single
      molecule fluorescence resonance energy transfer is presented. A genetically
      encoded unnatural ketone amino acid was labeled with a hydroxylamine-containing
      fluorophore with high yield (>95%) and specificity. This methodology was used to
      construct dual-labeled T4 lysozyme variants, allowing the study of T4 lysozyme
      folding at single-molecule resolution. The presented strategy is anticipated to
      expand the scope of single-molecule protein structure and function studies.

PMID- 19108699
TI  - Recombination of an Fe-Si-P linkage to an Fe-P-Si linkage through an isolable
      intermediate phosphasilaferracyclopropane.
AB  - Phosphasilaferracycle [Cp*(CO)Fe{kappa(2)Si,P-SiMe(2)PPh(2)}], prepared upon
      irradiation of [Cp*(CO)(2)FeSiMe(2)PPh(2)], was converted to
      [Cp*(CO)(2)FeP(Ph)SiMe(2)Ph] under mild conditions. The unusual recombination of
      the iron, silicon, and phosphorus cores could be achieved through a sequence of
      1,2- and 1,3-group migrations in an FeSiP system.

PMID- 19108700
TI  - A "kite" shaped styryl end-capped benzo[2,1-b:3,4-b']dithiophene with high
      electrical performances in organic thin film transistors.
AB  - The bridging of distyryl-bithiophene leads to a kite shape of the conjugated
      system. This twist is not like twistacenes or twist deformation in alpha
      oligothiophenes but a curvature such as in bowl shaped systems. Initially
      perceived to be undesirable, this new semiconductor in OTFT devices provides
      excellent performances in air, mu = 0.1 cm(2)/V.s, I(on)/I(off) > 10(6), S < 4
      V/decade, higher by a factor of 5 to the parent unbridged coplanar analogue.

PMID- 19108701
TI  - Structural and dynamics study of DNA dodecamer duplexes that contain un-, hemi-,
      or fully methylated GATC sites.
AB  - Methylation of DNA plays a regulatory role in DNA metabolism. The Escherichia
      coli DNA adenine methyltransferase methylates the N6 positions of adenines in the
      sequence 5'-GATC-3', which exists in the fully methylated state during most of
      the cell cycle. Just after DNA replication, however, the GATC sites transiently
      become hemimethylated, a condition that is indispensable for various cellular
      processes, such as negative modulation of replication initiation at oriC by SeqA.
      The lack of structural and dynamic information on DNA duplexes that contain fully
      methylated GATC sites makes it difficult to explain how hemimethylated GATC sites
      are recognized in vivo by proteins in a sea of fully methylated ones. Here, we
      used NMR spectroscopy to characterize the solution structure of a dodecamer DNA
      duplex that contained a fully methylated GATC site and the dynamics of the
      unmethylated, hemimethylated, and fully methylated GATC duplexes. Only the
      hemimethylated GATC duplex displays a unique major groove conformation, which is
      optimized for entrance into the cleft structure of SeqA. The apparent equilibrium
      constants for base-pair opening of the three differentially methylated GATC
      duplexes revealed that N6-methylation of the adenine residue affects the
      thermodynamics and kinetics of its own and neighboring base pairs. The
      equilibrium constants for base-pair opening of three GATC duplexes were
      determined using proton exchange catalyzed by TRIS. The two G.C base pairs of the
      hemimethylated GATC duplex displayed a faster base-pair opening rate and required
      less energy for the base-pair opening reaction than did those of the fully
      methylated one.

PMID- 19108705
TI  - The vacuolar ATPase from Entamoeba histolytica: molecular cloning of the gene
      encoding for the B subunit and subcellular localization of the protein.
AB  - BACKGROUND: Entamoeba histolytica is a professional phagocytic cell where the
      vacuolar ATPase plays a key role. This enzyme is a multisubunit complex that
      regulates pH in many subcellular compartments, even in those that are not
      measurably acidic. It participates in a wide variety of cellular processes such
      as endocytosis, intracellular transport and membrane fusion. The presence of a
      vacuolar type H+-ATPase in E. histolytica trophozoites has been inferred
      previously from inhibition assays of its activity, the isolation of the Ehvma1
      and Ehvma3 genes, and by proteomic analysis of purified phagosomes. RESULTS: We
      report the isolation and characterization of the Ehvma2 gene, which encodes for
      the subunit B of the vacuolar ATPase. This polypeptide is a 55.3 kDa highly
      conserved protein with 34 to 80% identity to orthologous proteins from other
      species. Particularly, in silico studies showed that EhV-ATPase subunit B
      displays 78% identity and 90% similarity to its Dictyostelium ortholog. A 462 bp
      DNA fragment of the Ehvma2 gene was expressed in bacteria and recombinant
      polypeptide was used to raise mouse polyclonal antibodies. EhV-ATPase subunit B
      antibodies detected a 55 kDa band in whole cell extracts and in an enriched
      fraction of DNA-containing organelles named EhkOs. The V-ATPase subunit B was
      located by immunofluorescence and confocal microscopy in many vesicles, in
      phagosomes, plasma membrane and in EhkOs. We also identified the genes encoding
      for the majority of the V-ATPase subunits in the E. histolytica genome, and
      proposed a putative model for this proton pump. CONCLUSION: We have isolated the
      Ehvma2 gene which encodes for the V-ATPase subunit B from the E. histolytica
      clone A. This gene has a 154 bp intron and encodes for a highly conserved
      polypeptide. Specific antibodies localized EhV-ATPase subunit B in many vesicles,
      phagosomes, plasma membrane and in EhkOs. Most of the orthologous genes encoding
      for the EhV-ATPase subunits were found in the E. histolytica genome, indicating
      the conserved nature of V-ATPase in this parasite.

PMID- 19108704
TI  - Clinical review: Critical care management of spontaneous intracerebral
      hemorrhage.
AB  - Intracerebral hemorrhage is by far the most destructive form of stroke. The
      clinical presentation is characterized by a rapidly deteriorating neurological
      exam coupled with signs and symptoms of elevated intracranial pressure. The
      diagnosis is easily established by the use of computed tomography or magnetic
      resonance imaging. Ventilatory support, blood pressure control, reversal of any
      preexisting coagulopathy, intracranial pressure monitoring, osmotherapy, fever
      control, seizure prophylaxis, treatment of hyerglycemia, and nutritional
      supplementation are the cornerstones of supportive care in the intensive care
      unit. Dexamethasone and other glucocorticoids should be avoided. Ventricular
      drainage should be performed urgently in all stuporous or comatose patients with
      intraventricular blood and acute hydrocephalus. Emergent surgical evacuation or
      hemicraniectomy should be considered for patients with large (>3 cm) cerebellar
      hemorrhages, and in those with large lobar hemorrhages, significant mass effect,
      and a deteriorating neurological exam. Apart from management in a specialized
      stroke or neurological intensive care unit, no specific medical therapies have
      been shown to consistently improve outcome after intracerebral hemorrhage.

PMID- 19108707
TI  - Validation of DNA probes for molecular cytogenetics by mapping onto immobilized
      circular DNA.
AB  - BACKGROUND: Fluorescence in situ hybridization (FISH) is a sensitive and rapid
      procedure to detect gene rearrangements in tumor cells using non-isotopically
      labeled DNA probes. Large insert recombinant DNA clones such as bacterial
      artificial chromosome (BAC) or P1/PAC clones have established themselves in
      recent years as preferred starting material for probe preparations due to their
      low rates of chimerism and ease of use. However, when developing probes for the
      quantitative analysis of rearrangements involving genomic intervals of less than
      100 kb, careful probe selection and characterization are of paramount importance.
      RESULTS: We describe a sensitive approach to quality control probe clones
      suspected of carrying deletions or for measuring clone overlap with near kilobase
      resolution. The method takes advantage of the fact that P1/PAC/BAC's can be
      isolated as circular DNA molecules, stretched out on glass slides and fine-mapped
      by multicolor hybridization with smaller probe molecules. Two examples
      demonstrate the application of this technique: mapping of a gene-specific ~6 kb
      plasmid onto an unusually small, ~55 kb circular P1 molecule and the
      determination of the extent of overlap between P1 molecules homologous to the
      human NF-kappaB2 locus. CONCLUSION: The relatively simple method presented here
      does not require specialized equipment and may thus find widespread applications
      in DNA probe preparation and characterization, the assembly of physical maps for
      model organisms or in studies on gene rearrangements.

PMID- 19108706
TI  - An evolutionary and structural characterization of mammalian protein complex
      organization.
AB  - BACKGROUND: We have recently released a comprehensive, manually curated database
      of mammalian protein complexes called CORUM. Combining CORUM with other
      resources, we assembled a dataset of over 2700 mammalian complexes. The
      availability of a rich information resource allows us to search for
      organizational properties concerning these complexes. RESULTS: As the complexity
      of a protein complex in terms of the number of unique subunits increases, we
      observed that the number of such complexes and the mean non-synonymous to
      synonymous substitution ratio of associated genes tend to decrease. Similarly, as
      the number of different complexes a given protein participates in increases, the
      number of such proteins and the substitution ratio of the associated gene also
      tends to decrease. These observations provide evidence relating natural selection
      and the organization of mammalian complexes. We also observed greater homogeneity
      in terms of predicted protein isoelectric points, secondary structure and
      substitution ratio in annotated versus randomly generated complexes. A large
      proportion of the protein content and interactions in the complexes could be
      predicted from known binary protein-protein and domain-domain interactions. In
      particular, we found that large proteins interact preferentially with much
      smaller proteins. CONCLUSION: We observed similar trends in yeast and other data.
      Our results support the existence of conserved relations associated with the
      mammalian protein complexes.

PMID- 19108708
TI  - Right subclavian double steal syndrome: a case report.
AB  - INTRODUCTION: Double-steal syndrome represents a causative factor for blood flow
      compromise of the cerebral vascular bed with transient neurologic symptoms. We
      present the case of a patient with innominate artery atherosclerotic occlusion,
      manifested as blood flow reversal in the vertebral and common carotid arteries.
      Symptomatic atherosclerotic occlusive disease of the innominate artery is
      relatively rare and represents less than 2% of all extracranial causes of
      cerebrovascular insufficiency. CASE PRESENTATION: We report on a 73-year-old male
      patient who presented at our hospital for the evaluation of dizziness and
      episodes of syncope. Angiography and color Doppler examinations documented the
      double syndrome as retrograde flow in the right vertebral artery and the right
      carotid artery. CONCLUSION: Constituting an indication for surgical correction,
      his condition was managed with the performance of carotid-carotid extra-anatomic
      bypass for the permanent reestablishment of antegrade blood flow in the vascular
      network supplying the brain. Carotid-carotid extra-anatomic bypass was a good
      option for our patient, since he remains symptom free after one year of follow
      up.

PMID- 19108709
TI  - Eptifibatide and abciximab inhibit insulin-induced focal adhesion formation and
      proliferative responses in human aortic smooth muscle cells.
AB  - BACKGROUND: The use of abciximab (c7E3 Fab) or eptifibatide improves clinical
      outcomes in diabetics undergoing percutaneous coronary intervention. These beta3
      integrin inhibitors antagonize fibrinogen binding to alphaIIbbeta3 integrins on
      platelets and ligand binding to alphavbeta3 integrins on vascular cells.
      alphavbeta3 integrins influence responses to insulin in various cell types but
      effects in human aortic smooth muscle cells (HASMC) are unknown. RESULTS AND
      DISCUSSION: Insulin elicited a dose-dependent proliferative response in HASMC.
      Pretreatment with m7E3 (an anti-beta3 integrin monoclonal antibody from which
      abciximab is derived), c7E3 or LM609 inhibited proliferative responses to insulin
      by 81%, 59% and 28%, respectively. Eptifibatide or cyclic RGD peptides completely
      abolished insulin-induced proliferation whereas tirofiban, which binds
      alphaIIbbeta3 but not alphavbeta3, had no effect. Insulin-induced increases in c
      Jun NH2-terminal kinase-1 (JNK1) activity were partially inhibited by m7E3 and
      eptifibatide whereas antagonism of alphavbeta3 integrins had no effect on insulin
      induced increases in extracellular signal-regulated kinase (ERK) activity.
      Insulin stimulated a rapid increase in the number of vinculin-containing focal
      adhesions per cell and treatment with m7E3, c7E3 or eptifibatide inhibited
      insulin-induced increases in focal adhesions by 100%, 74% and 73%, respectively.
      CONCLUSION: These results demonstrate that alphavbeta3 antagonists inhibit
      signaling, focal adhesion formation and proliferation of insulin-treated HASMC.

PMID- 19108710
TI  - Meta-analysis of expression signatures of muscle atrophy: gene interaction
      networks in early and late stages.
AB  - BACKGROUND: Skeletal muscle mass can be markedly reduced through a process called
      atrophy, as a consequence of many diseases or critical physiological and
      environmental situations. Atrophy is characterised by loss of contractile
      proteins and reduction of fiber volume. Although in the last decade the molecular
      aspects underlying muscle atrophy have received increased attention, the fine
      mechanisms controlling muscle degeneration are still incomplete. In this study we
      applied meta-analysis on gene expression signatures pertaining to different types
      of muscle atrophy for the identification of novel key regulatory signals
      implicated in these degenerative processes. RESULTS: We found a general down
      regulation of genes involved in energy production and carbohydrate metabolism and
      up-regulation of genes for protein degradation and catabolism. Six functional
      pathways occupy central positions in the molecular network obtained by the
      integration of atrophy transcriptome and molecular interaction data. They are TGF
      beta pathway, apoptosis, membrane trafficking/cytoskeleton organization, NFKB
      pathways, inflammation and reorganization of the extracellular matrix. Protein
      degradation pathway is evident only in the network specific for muscle short-term
      response to atrophy. TGF-beta pathway plays a central role with proteins SMAD3/4,
      MYC, MAX and CDKN1A in the general network, and JUN, MYC, GNB2L1/RACK1 in the
      short-term muscle response network. CONCLUSION: Our study offers a general
      overview of the molecular pathways and cellular processes regulating the
      establishment and maintenance of atrophic state in skeletal muscle, showing also
      how the different pathways are interconnected. This analysis identifies novel key
      factors that could be further investigated as potential targets for the
      development of therapeutic treatments. We suggest that the transcription factors
      SMAD3/4, GNB2L1/RACK1, MYC, MAX and JUN, whose functions have been extensively
      studied in tumours but only marginally in muscle, appear instead to play
      important roles in regulating muscle response to atrophy.

PMID- 19108711
TI  - Gene transfer of GLT-1, a glial glutamate transporter, into the spinal cord by
      recombinant adenovirus attenuates inflammatory and neuropathic pain in rats.
AB  - BACKGROUND: The glial glutamate transporter GLT-1 is abundantly expressed in
      astrocytes and is crucial for glutamate removal from the synaptic cleft.
      Decreases in glutamate uptake activity and expression of spinal glutamate
      transporters are reported in animal models of pathological pain. However, the
      lack of available specific inhibitors and/or activators for GLT-1 makes it
      difficult to determine the roles of spinal GLT-1 in inflammatory and neuropathic
      pain. In this study, we examined the effect of gene transfer of GLT-1 into the
      spinal cord with recombinant adenoviruses on the inflammatory and neuropathic
      pain in rats. RESULTS: Intraspinal infusion of adenoviral vectors expressing the
      GLT-1 gene increased GLT-1 expression in the spinal cord 2-21 days after the
      infusion. Transgene expression was primarily localized to astrocytes. The spinal
      GLT-1 gene transfer had no effect on acute mechanical and thermal nociceptive
      responses in naive rats, whereas it significantly reduced the inflammatory
      mechanical hyperalgesia induced by hindlimb intraplantar injection of
      carrageenan/kaolin. Spinal GLT-1 gene transfer 7 days before partial sciatic
      nerve ligation recovered the extent of the spinal GLT-1 expression in the
      membrane fraction that was decreased following the nerve ligation, and prevented
      the induction of tactile allodynia. However, the partial sciatic nerve ligation
      induced allodynia was not reversed when the adenoviruses were infused 7 or 14
      days after the nerve ligation. CONCLUSION: These results suggest that
      overexpression of GLT-1 on astrocytes in the spinal cord by recombinant
      adenoviruses attenuates the induction, but not maintenance, of inflammatory and
      neuropathic pain, probably by preventing the induction of central sensitization,
      without affecting acute pain sensation. Upregulation or functional enhancement of
      spinal GLT-1 could be a novel strategy for the prevention of pathological pain.

PMID- 19108712
TI  - Global gene expression analyses of bystander and alpha particle irradiated normal
      human lung fibroblasts: synchronous and differential responses.
AB  - BACKGROUND: The existence of a radiation bystander effect, in which non
      irradiated cells respond to signals from irradiated cells, is now well
      established. It raises concerns for the interpretation of risks arising from
      exposure to low doses of ionizing radiation. However, the regulatory mechanisms
      involved in the bystander response have not been well elucidated. To provide
      insight into the signaling pathways responding in bystanders, we have measured
      global gene expression four hours after bystander and direct alpha particle
      exposure of primary human lung fibroblasts. RESULTS: Although common p53
      regulated radiation response genes like CDKN1A were expressed at elevated levels
      in the directly exposed cultures, they showed little or no change in the
      bystanders. In contrast, genes regulated by NFkappaB, such as PTGS2
      (cyclooxygenase-2), IL8 and BCL2A1, responded nearly identically in bystander and
      irradiated cells. This trend was substantiated by gene ontology and pathway
      analyses of the microarray data, which suggest that bystander cells mount a full
      NFkappaB response, but a muted or partial p53 response. In time-course analyses,
      quantitative real-time PCR measurements of CDKN1A showed the expected 4-hour peak
      of expression in irradiated but not bystander cells. In contrast, PTGS2, IL8 and
      BCL2A1 responded with two waves of expression in both bystander and directly
      irradiated cells, one peaking at half an hour and the other between four and six
      hours after irradiation. CONCLUSION: Two major transcriptional hubs that regulate
      the direct response to ionizing radiation are also implicated in regulation of
      the bystander response, but to dramatically different degrees. While activation
      of the p53 response pathway is minimal in bystander cells, the NFkappaB response
      is virtually identical in irradiated and bystander cells. This alteration in the
      balance of signaling is likely to lead to different outcomes in irradiated cells
      and their bystanders, perhaps leading to greater survival of bystanders and
      increased risk from any long-term damage they have sustained.

PMID- 19108713
TI  - Nestin and CD133: valuable stem cell-specific markers for determining clinical
      outcome of glioma patients.
AB  - AIM: Gliomas represent the most frequent neoplasm of the central nervous system.
      Unfortunately, surgical cure of it is practically impossible and their clinical
      course is primarily determined by the biological behaviors of the tumor cells.
      The aim of this study was to investigate the correlation of the stem cell markers
      Nestin and CD133 expression with the grading of gliomas, and to evaluate their
      prognostic value. METHODS: The tissue samples consisted of 56 low- (WHO grade
      II), 69 high- (WHO grade III, IV) grade gliomas, and 10 normal brain tissues. The
      expression levels of Nestin and CD133 proteins were detected using SABC
      immunohistochemical analysis. Then, the correlation of the two markers'
      expression with gliomas' grading of patients and their prognostic value were
      determined. RESULTS: Immunohistochemical analysis with anti-Nestin and anti-CD133
      antibodies revealed dense and spotty staining in the tumor cells and their
      expression levels became significantly higher as the glioma grade advanced (p <
      0.05). There was a positive correlation between the two markers' expression in
      different gliomas tissues (rs = 0.89). The low expression of the two markers
      significantly correlated with long survival of the glioma patients (p < 0.05).
      The survival rate of the patients with Nestin+/CD133+ expression was the lowest
      (p < 0.01), and the multivariate analysis confirmed that conjoined expression of
      Nestin+/CD133+ and Nestin-/CD133- were independent prognostic indicators of
      gliomas (both p < 0.01, Cox proportional hazard regression model). CONCLUSION:
      These results collectively suggest that Nestin and CD133 expression may be an
      important feature of human gliomas. A combined detection of Nestin/CD133 co
      expression may benefit us in the prediction of aggressive nature of this tumor.

PMID- 19108714
TI  - A large-scale survey of genetic copy number variations among Han Chinese residing
      in Taiwan.
AB  - BACKGROUND: Copy number variations (CNVs) have recently been recognized as
      important structural variations in the human genome. CNVs can affect gene
      expression and thus may contribute to phenotypic differences. The copy number
      inferring tool (CNIT) is an effective hidden Markov model-based algorithm for
      estimating allele-specific copy number and predicting chromosomal alterations
      from single nucleotide polymorphism microarrays. The CNIT algorithm, which was
      constructed using data from 270 HapMap multi-ethnic individuals, was applied to
      identify CNVs from 300 unrelated Han Chinese individuals in Taiwan. RESULTS:
      Using stringent selection criteria, 230 regions with variable copy numbers were
      identified in the Han Chinese population; 133 (57.83%) had been reported
      previously, 64 displayed greater than 1% CNV allele frequency. The average size
      of the CNV regions was 322 kb (ranging from 1.48 kb to 5.68 Mb) and covered a
      total of 2.47% of the human genome. A total of 196 of the CNV regions were simple
      deletions and 27 were simple amplifications. There were 449 genes and 5 microRNAs
      within these CNV regions; some of these genes are known to be associated with
      diseases. CONCLUSION: The identified CNVs are characteristic of the Han Chinese
      population and should be considered when genetic studies are conducted. The CNV
      distribution in the human genome is still poorly characterized, and there is much
      diversity among different ethnic populations.

PMID- 19108715
TI  - Forced IFIT-2 expression represses LPS induced TNF-alpha expression at
      posttranscriptional levels.
AB  - BACKGROUND: Interferon induced tetratricopeptide repeat protein 2 (IFIT-2, P54)
      belongs to the type I interferon response genes and is highly induced after
      stimulation with LPS. The biological function of this protein is so far unclear.
      Previous studies indicated that IFIT-2 binds to the initiation factor subunit eIF
      3c, affects translation initiation and inhibits protein synthesis. The aim of the
      study was to further characterize the function of IFIT-2. RESULTS: Stimulation of
      RAW264.7 macrophages with LPS or IFN-gamma leads to the expression of IFIT-2 in a
      type I interferon dependent manner. By using stably transfected RAW264.7
      macrophages overexpressing IFIT-2 we found that IFIT-2 inhibits selectively LPS
      induced expression of TNF-alpha, IL-6, and MIP-2 but not of IFIT-1 or EGR-1. In
      IFIT-2 overexpressing cells TNF-alpha mRNA expression was lower after LPS
      stimulation due to reduced mRNA stability. Further experiments suggest that
      characteristics of the 3'UTR of transcripts discriminate whether IFIT-2 has a
      strong impact on protein expression or not. CONCLUSION: Our data suggest that
      IFIT-2 may affect selectively LPS induced protein expression probably by
      regulation at different posttranscriptional levels.

PMID- 19108716
TI  - Arabidopsis eIF2alpha kinase GCN2 is essential for growth in stress conditions
      and is activated by wounding.
AB  - BACKGROUND: Phosphorylation of eIF2alpha provides a key mechanism for down
      regulating protein synthesis in response to nutrient starvation or stresses in
      mammalian and yeast cells. However, this process has not been well characterized
      in plants RESULTS: We show here that in response to amino acid and purine
      starvations, UV, cold shock and wounding, the Arabidopsis GCN2 kinase (AtGCN2) is
      activated and phosphorylates eIF2alpha. We show that AtGCN2 is essential for
      plant growth in stress situations and that its activity results in a strong
      reduction in global protein synthesis. CONCLUSION: Our results suggest that a
      general amino acid control response is conserved between yeast and plants but
      that the plant enzyme evolved to fulfill a more general function as an upstream
      sensor and regulator of diverse stress-response pathways. The activation of
      AtGCN2 following wounding or exposure to methyl jasmonate, the ethylene precursor
      1-Aminocyclopropane-1-carboxylic acid (ACC) and salicylic acid, further suggests
      that this enzyme could play a role in plant defense against insect herbivores.

PMID- 19108717
TI  - Recovery from a cycling time trial is enhanced with carbohydrate-protein
      supplementation vs. isoenergetic carbohydrate supplementation.
AB  - BACKGROUND: In this study we assessed whether a liquid carbohydrate-protein (C+P)
      supplement (0.8 g/kg C; 0.4 g/kg P) ingested early during recovery from a cycling
      time trial could enhance a subsequent 60 min effort on the same day vs. an
      isoenergetic liquid carbohydrate (CHO) supplement (1.2 g/kg). METHODS: Two hours
      after a standardized breakfast, 15 trained male cyclists completed a time trial
      in which they cycled as far as they could in 60 min (AM(ex)) using a Computrainer
      indoor trainer. Following AM(ex), subjects ingested either C+P, or CHO at 10, 60
      and 120 min, followed by a standardized meal at 4 h post exercise. At 6 h post
      AM(ex) subjects repeated the time trial (PM(ex)). RESULTS: There was a
      significant reduction in performance for both groups in PM(ex) versus AM(ex).
      However, performance and power decreases between PM(ex) and AM(ex) were
      significantly greater (p </= 0.05) with CHO (-1.05 +/- 0.44 km and -16.50 +/-
      6.74 W) vs C+P (-0.30 +/- 0.50 km and -3.86 +/- 6.47 W). Fat oxidation estimated
      from RER values was significantly greater (p </= 0.05) in the C+P vs CHO during
      the PM(ex), despite a higher average workload in the C+P group. CONCLUSION: Under
      these experimental conditions, liquid C+P ingestion immediately after exercise
      increases fat oxidation, increases recovery, and improves subsequent same day, 60
      min efforts relative to isoenergetic CHO ingestion.

PMID- 19108718
TI  - Normative productivity of the global vegetation.
AB  - BACKGROUND: The biosphere models of terrestrial productivity are essential for
      projecting climate change and assessing mitigation and adaptation options. Many
      of them have been developed in connection to the International Geosphere
      Biosphere Program (IGBP) that backs the work of the Intergovernmental Panel on
      Climate Change (IPCC). In the end of 1990s, IGBP sponsored release of a data set
      summarizing the model outputs and setting certain norms for estimates of
      terrestrial productivity. Since a number of new models and new versions of old
      models were developed during the past decade, these normative data require
      updating. RESULTS: Here, we provide the series of updates that reflects evolution
      of biosphere models and demonstrates evolutional stability of the global and
      regional estimates of terrestrial productivity. Most of them fit well the long
      living Miami model. At the same time we call attention to the emerging
      alternative: the global potential for net primary production of biomass may be as
      high as 70 PgC y-1, the productivity of larch forest zone may be comparable to
      the productivity of taiga zone, and the productivity of rain-green forest zone
      may be comparable to the productivity of tropical rainforest zone. CONCLUSION:
      The departure from Miami model's worldview mentioned above cannot be simply
      ignored. It requires thorough examination using modern observational tools and
      techniques for model-data fusion. Stability of normative knowledge is not its
      ultimate goal - the norms for estimates of terrestrial productivity must be
      evidence-based.

PMID- 19108719
TI  - Young carers in Germany: to live on as normal as possible - a grounded theory
      study.
AB  - BACKGROUND: In contrast to a growing body of research on the situation of adult
      family care givers, in Germany hardly anything is known about the situation of
      children and teenagers who are involved in the care of their relatives. METHODS:
      In this Grounded Theory study 81 semi structured interviews have been carried out
      with children and their parents in 34 families, in which one member is
      chronically ill. 41 children and 41 parents participated and the sample is
      heterogeneous and diverse. RESULTS: On the one hand, there is the phenomenon
      'keeping the family together", which describes how families themselves cope with
      the chronic illness and also, which tasks to what extent are being shifted and
      redistributed within the family in order to manage daily life. Influencing
      factors, the children's motives as well as the impact on the children also belong
      to this phenomenon. The second phenomenon 'to live a normal course of life'
      describes concrete wishes and expectations of support for the family to manage
      the hindered daily life. These two phenomena linked together constitute the
      'model of experience and construction of familial care, in which children take
      over an active role'. CONCLUSION: It will be discussed, that the more families
      are in dire need of support, the more their distress becomes invisible,
      furthermore, that management of chronic illness is a process, in which the entire
      family is involved, and thus needs to be considered, and finally, that young
      carer's relief is not possible without relief of their parents.

PMID- 19108720
TI  - Oceanic dispersal barriers, adaptation and larval retention: an interdisciplinary
      assessment of potential factors maintaining a phylogeographic break between
      sister lineages of an African prawn.
AB  - BACKGROUND: Genetic breaks separating regional lineages of marine organisms with
      potentially high broadcasting abilities are generally attributed either to
      dispersal barriers such as currents or upwelling, or to behavioural strategies
      promoting self-recruitment. We investigated whether such patterns could
      potentially also be explained by adaptations to different environmental
      conditions by studying two morphologically distinguishable genetic lineages of
      the estuarine mudprawn Upogebia africana across a biogeographic disjunction in
      south-eastern Africa. The study area encompasses a transition between temperate
      and subtropical biotas, where the warm, southward-flowing Agulhas Current is
      deflected away from the coast, and its inshore edge is characterised by
      intermittent upwelling. To determine how this phylogeographic break is
      maintained, we estimated gene flow among populations in the region, tested for
      isolation by distance as an indication of larval retention, and reared larvae of
      the temperate and subtropical lineages at a range of different temperatures.
      RESULTS: Of four populations sampled, the two northernmost exclusively included
      the subtropical lineage, a central population had a mixture of both lineages, and
      the southernmost estuary had only haplotypes of the temperate lineage. No
      evidence was found for isolation by distance, and gene flow was bidirectional and
      of similar magnitude among adjacent populations. In both lineages, the optimum
      temperature for larval development was at about 23 degrees C, but a clear
      difference was found at lower temperatures. While larvae of the temperate lineage
      could complete development at temperatures as low as 12 degrees C, those of the
      subtropical lineage did not complete development below 17 degrees C. CONCLUSION:
      The results indicate that both southward dispersal of the subtropical lineage
      inshore of the Agulhas Current, and its establishment in the temperate province,
      may be limited primarily by low water temperatures. There is no evidence that the
      larvae of the temperate lineage would survive less well in the subtropical
      province than in their native habitat, and their exclusion from this region may
      be due to a combination of upwelling, short larval duration with limited
      dispersal potential near the coast, plus transport away from the coast of larvae
      that become entrained in the Agulhas Current. This study shows how methods from
      different fields of research (genetics, physiology, oceanography and morphology)
      can be combined to study phylogeographic patterns.

PMID- 19108721
TI  - Subcellular localization of ammonium transporters in Dictyostelium discoideum.
AB  - BACKGROUND: With the exception of vertebrates, most organisms have plasma
      membrane associated ammonium transporters which primarily serve to import a
      source of nitrogen for nutritional purposes. Dictyostelium discoideum has three
      ammonium transporters, Amts A, B and C. Our present work used fluorescent fusion
      proteins to determine the cellular localization of the Amts and tested the
      hypothesis that the transporters mediate removal of ammonia generated
      endogenously from the elevated protein catabolism common to many protists.
      RESULTS: Using RFP and YFP fusion constructs driven by the actin 15 promoter, we
      found that the three ammonium transporters were localized on the plasma membrane
      and on the membranes of subcellular organelles. AmtA and AmtB were localized on
      the membranes of endolysosomes and phagosomes, with AmtB further localized on the
      membranes of contractile vacuoles. AmtC also was localized on subcellular
      organelles when it was stabilized by coexpression with either the AmtA or AmtB
      fusion transporter. The three ammonium transporters exported ammonia linearly
      with regard to time during the first 18 hours of the developmental program as
      revealed by reduced export in the null strains. The fluorescently tagged
      transporters rescued export when expressed in the null strains, and thus they
      were functional transporters. CONCLUSION: Unlike ammonium transporters in most
      organisms, which import NH3/NH4+ as a nitrogen source, those of Dictyostelium
      export ammonia/ammonium as a waste product from extensive catabolism of
      exogenously derived and endogenous proteins. Localization on proteolytic
      organelles and on the neutral contractile vacuole suggests that Dictyostelium
      ammonium transporters may have unique subcellular functions and play a role in
      the maintenance of intracellular ammonium distribution. A lack of correlation
      between the null strain phenotypes and ammonia excretion properties of the
      ammonium transporters suggests that it is not the excretion function that is
      important for coupling ammonia levels to the slug versus culmination choice, but
      rather a sensor and/or signaling function of these proteins that is important.

PMID- 19108722
TI  - Genotyping and drug resistance patterns of M. tuberculosis strains in Pakistan.
AB  - BACKGROUND: The incidence of tuberculosis in Pakistan is 181/100,000 population.
      However, information about transmission and geographical prevalence of
      Mycobacterium tuberculosis strains and their evolutionary genetics as well as
      drug resistance remains limited. Our objective was to determine the clonal
      composition, evolutionary genetics and drug resistance of M. tuberculosis
      isolates from different regions of the country. METHODS: M. tuberculosis strains
      isolated (2003-2005) from specimens submitted to the laboratory through
      collection units nationwide were included. Drug susceptibility was performed and
      strains were spoligotyped. RESULTS: Of 926 M. tuberculosis strains studied,
      721(78%) were grouped into 59 "shared types", while 205 (22%) were identified as
      "Orphan" spoligotypes. Amongst the predominant genotypes 61% were Central Asian
      strains (CAS ; including CAS1, CAS sub-families and Orphan Pak clusters), 4% East
      African-Indian (EAI), 3% Beijing, 2% poorly defined TB strains (T), 2% Haarlem
      and LAM (0.2). Also TbD1 analysis (M. tuberculosis specific deletion 1) confirmed
      that CAS1 was of "modern" origin while EAI isolates belonged to "ancestral"
      strain types.Prevalence of CAS1 clade was significantly higher in Punjab (P <
      0.01, Pearsons Chi-square test) as compared with Sindh, North West Frontier
      Province and Balochistan provinces. Forty six percent of isolates were sensitive
      to five first line antibiotics tested, 45% were Rifampicin resistant, 50%
      isoniazid resistant. MDR was significantly associated with Beijing strains (P =
      0.01, Pearsons Chi-square test) and EAI (P = 0.001, Pearsons Chi-square test),
      but not with CAS family. CONCLUSION: Our results show variation of prevalent M.
      tuberculosis strain with greater association of CAS1 with the Punjab province.
      The fact that the prevalent CAS genotype was not associated with drug resistance
      is encouraging. It further suggests a more effective treatment and control
      programme should be successful in reducing the tuberculosis burden in Pakistan.

PMID- 19108724
TI  - Social inequalities in mental health in Norway: possible explanatory factors.
AB  - BACKGROUND: It is well known that there is a social gradient in mental health,
      the prevalence of mental disorders stepwise increasing by lower social status.
      The reason for this, however, is not clear, and the purpose of the present study
      was to explore possible mediating factors between social status and mental
      health. METHODS: The study has a cross-sectional design, and was based on a
      nationwide survey in Oslo, Norway, counting 12 310 people in the age of 30-60
      years. Immigrants from non-western countries were excluded. Socio-demographic
      data were gathered from existing registers, whereas data on health, psychosocial
      variables and life style were gathered by structured interview. As indicator of
      mental health was used a 10-items version of Hopkins Symptom Checklist, measuring
      psychological distress. Measures of general self-efficacy and sense of
      powerlessness was used as indicators of control of own life situation. RESULTS: A
      strong social gradient in mental health was found, the prevalence of
      psychological distress increasing by decreasing social status. Psychosocial
      factors, including self-efficacy, sense of powerlessness, control of work, social
      support and negative life events, in particular economic problems, as well as
      life style factors (physical exercise, BMI, smoking) and somatic health, likewise
      showed a social gradient, all risk factors increasing by decreasing social
      status. When adjusting for the risk factors in multivariate statistical analyses,
      the social gradient in mental health was eliminated. Low self-efficacy and sense
      of powerlessness emerged as important explanatory factors, alongside with poor
      social support, economic problems, smoking and somatic disorder. CONCLUSION: Both
      individual characteristics, supposedly linked to the personality, like low self
      efficacy, and factors related to the actual life situation, like economic
      problems and a feeling of powerlessness, contribute to the social gradient in
      mental health, and both aspects should be addressed in preventive work.

PMID- 19108723
TI  - Improving the cost-effectiveness of IRS with climate informed health surveillance
      systems.
AB  - BACKGROUND: This paper examines how the cost-effectiveness of IRS varies
      depending on the severity of transmission and level of programme coverage and how
      efficiency could be improved by incorporating climate information into decision
      making for malaria control programmes as part of an integrated Malaria Early
      Warning and Response System (MEWS). METHODS: A climate driven model of malaria
      transmission was used to simulate cost-effectiveness of alternative IRS coverage
      levels over six epidemic and non-epidemic years. Decision rules for a potential
      MEWS system that triggers different IRS coverage are described. The average and
      marginal cost per case averted with baseline IRS coverage (24%) and under varying
      IRS coverage levels (50%, 75% and 100%) were calculated. RESULTS: Average cost
      effectiveness of 24% coverage varies dramatically between years, from US$108 per
      case prevented in low transmission to US$0.42 in epidemic years. Similarly for
      higher coverage (24-100%) cost per case prevented is far higher in low than high
      transmission years ($108-$267 to $0.88-$2.26). DISCUSSION: Efficiency and health
      benefit gains could be achieved by implementing MEWS that provides timely,
      accurate information. Evidence from southern Africa, (especially Botswana)
      supports this. CONCLUSION: Advance knowledge of transmission severity can help
      managers make coverage decisions which optimise resource use and exploit
      efficiency gains if a fully integrated MEWS is in place alongside a health system
      with sufficient flexibility to modify control plans in response to information.
      More countries and programmes should be supported to use the best available
      evidence and science to integrate climate informed MEWS into decision making
      within malaria control programmes.

PMID- 19108725
TI  - Sex between men in the context of HIV: The AIDS 2008 Jonathan Mann Memorial
      Lecture in health and human rights.
AB  - Gay, bisexual, and other men who have sex with men (MSM) have been among the
      most affected populations by HIV since the AIDS pandemic was first identified in
      the 1980s. Evidence from a wide range of studies show that these men remain at
      the highest risk for HIV acquisition in both developed and developing countries,
      and that despite three decades of evidence of their vulnerability to HIV, they
      remain under-served and under-studied. Prevention strategies targeted to MSM are
      markedly under-funded in most countries, leading to limited access to health
      services including prevention, treatment, and care. We explore the global
      epidemic among MSM in 2008, the limited funding available globally to respond to
      these epidemics, and the human rights contexts and factors which drive HIV spread
      and limit HIV responses for these men.What do we mean by the term MSM? MSM is a
      construct from the 1990s that tries to capture behavior and not identity. It was
      crafted to avoid stigmatizing and culturally laden terms such as gay or bisexual,
      which do not capture the wide diversity of orientations, sexual practices,
      cultures, and contextual settings in which male same-sex behaviors occur, and
      where HIV transmission and acquisition risks are centered. MSM includes both gay
      and non-gay identified men, bisexual men, and MSM who identify themselves as
      heterosexuals. It also includes men engaging in "situational" sex between men,
      such as can occur in prisons, schools, militaries or other environments; and it
      includes male sex workers who may be of any orientation but are often at very
      high risk for HIV. MSM may include some biologically male transgender persons,
      though some do not identify as male. And MSM includes a wide array of traditional
      and local terms worldwide-with enormous cultural diversity in Asia, Africa, Latin
      America and elsewhere. We use the term MSM here at its most inclusive.

PMID- 19108726
TI  - More than just needles: an evidence-informed approach to enhancing harm reduction
      supply distribution in British Columbia.
AB  - BACKGROUND: The BC Harm Reduction Strategies and Services (HRSS) policy states
      that each health authority (HA) and their community partners will provide a full
      range of harm reduction (HR) services to their jurisdictions and these HR
      products should be available to all who need them regardless of where they live
      and choice of drug. Preliminary analysis revealed wide variations between and
      within HAs. METHODS: The objective of this study is to analyze distribution of HR
      products by site using Geographic Information Systems (GIS) and to investigate
      the range, adequacy and methods of HR product distribution using qualitative
      interviews. The BC Centre for Disease Control pharmacy database tracks HR
      supplies distributed to health units and community agencies. Additionally, eleven
      face-to-face interviews were conducted in eight mainland BC communities using an
      open-ended questionnaire. RESULTS: There is evidence in BC that HR supplies are
      not equally available throughout the province. There are variations within
      jurisdictions in how HR supplies are distributed, adequacy of current HR
      products, collection of used needles, alternative uses of supplies and community
      attitudes towards HR. GIS illustrates where HR supplies are ordered but with
      secondary distribution, true reach and availability of supplies cannot be
      determined. CONCLUSION: Currently, a consultant is employed to develop a 'best
      practice' document; relevant health files, standard training and protocols within
      HAs are also being developed. There is a need to enhance the profile and
      availability of culturally appropriate HR services for Aboriginal populations.
      Distribution of crackpipe mouthpieces is being investigated.

PMID- 19108728
TI  - Histoplasma capsulatum proteome response to decreased iron availability.
AB  - BACKGROUND: A fundamental pathogenic feature of the fungus Histoplasma capsulatum
      is its ability to evade innate and adaptive immune defenses. Once ingested by
      macrophages the organism is faced with several hostile environmental conditions
      including iron limitation. H. capsulatum can establish a persistent state within
      the macrophage. A gap in knowledge exists because the identities and number of
      proteins regulated by the organism under host conditions has yet to be defined.
      Lack of such knowledge is an important problem because until these proteins are
      identified it is unlikely that they can be targeted as new and innovative
      treatment for histoplasmosis. RESULTS: To investigate the proteomic response by
      H. capsulatum to decreasing iron availability we have created H. capsulatum
      protein/genomic databases compatible with current mass spectrometric (MS) search
      engines. Databases were assembled from the H. capsulatum G217B strain genome
      using gene prediction programs and expressed sequence tag (EST) libraries.
      Searching these databases with MS data generated from two dimensional (2D) in-gel
      digestions of proteins resulted in over 50% more proteins identified compared to
      searching the publicly available fungal databases alone. Using 2D gel
      electrophoresis combined with statistical analysis we discovered 42 H. capsulatum
      proteins whose abundance was significantly modulated when iron concentrations
      were lowered. Altered proteins were identified by mass spectrometry and database
      searching to be involved in glycolysis, the tricarboxylic acid cycle, lysine
      metabolism, protein synthesis, and one protein sequence whose function was
      unknown. CONCLUSION: We have created a bioinformatics platform for H. capsulatum
      and demonstrated the utility of a proteomic approach by identifying a shift in
      metabolism the organism utilizes to cope with the hostile conditions provided by
      the host. We have shown that enzyme transcripts regulated by other fungal
      pathogens in response to lowering iron availability are also regulated in H.
      capsulatum at the protein level. We also identified H. capsulatum proteins
      sensitive to iron level reductions which have yet to be connected to iron
      availability in other pathogens. These data also indicate the complexity of the
      response by H. capsulatum to nutritional deprivation. Finally, we demonstrate the
      importance of a strain specific gene/protein database for H. capsulatum proteomic
      analysis.

PMID- 19108727
TI  - Ephrin-B2 expression critically influences Nipah virus infection independent of
      its cytoplasmic tail.
AB  - BACKGROUND: Cell entry and cell-to-cell spread of the highly pathogenic Nipah
      virus (NiV) requires binding of the NiV G protein to cellular ephrin receptors
      and subsequent NiV F-mediated fusion. Since expression levels of the main NiV
      entry receptor ephrin-B2 (EB2) are highly regulated in vivo to fulfill the
      physiological functions in axon guidance and angiogenesis, the goal of this study
      was to determine if changes in the EB2 expression influence NiV infection.
      RESULTS: Surprisingly, transfection of increasing EB2 plasmid concentrations
      reduced cell-to-cell fusion both in cells expressing the NiV glycoproteins and in
      cells infected with NiV. This effect was attributed to the downregulation of the
      NiV glycoproteins from the cell surface. In addition to the influence on cell-to
      cell fusion, increased EB2 expression significantly reduced the total amount of
      NiV-infected cells, thus interfered with virus entry. To determine if the
      negative effect of elevated EB2 expression on virus entry is a result of an
      increased EB2 signaling, receptor function of a tail-truncated and therefore
      signaling-defective DeltacEB2 was tested. Interestingly, DeltacEB2 fully
      functioned as NiV entry and fusion receptor, and overexpression also interfered
      with virus replication. CONCLUSION: Our findings clearly show that EB2 signaling
      does not account for the striking negative impact of elevated receptor expression
      on NiV infection, but rather that the ratio between the NiV envelope
      glycoproteins and surface receptors critically influence cell-to-cell fusion and
      virus entry.

PMID- 19108729
TI  - A first generation whole genome RH map of the river buffalo with comparison to
      domestic cattle.
AB  - BACKGROUND: The recently constructed river buffalo whole-genome radiation hybrid
      panel (BBURH5000) has already been used to generate preliminary radiation hybrid
      (RH) maps for several chromosomes, and buffalo-bovine comparative chromosome maps
      have been constructed. Here, we present the first-generation whole genome RH map
      (WG-RH) of the river buffalo generated from cattle-derived markers. The RH maps
      aligned to bovine genome sequence assembly Btau_4.0, providing valuable
      comparative mapping information for both species. RESULTS: A total of 3990
      markers were typed on the BBURH5000 panel, of which 3072 were cattle derived
      SNPs. The remaining 918 were classified as cattle sequence tagged site (STS),
      including coding genes, ESTs, and microsatellites. Average retention frequency
      per chromosome was 27.3% calculated with 3093 scorable markers distributed in 43
      linkage groups covering all autosomes (24) and the X chromosomes at a LOD >or= 8.
      The estimated total length of the WG-RH map is 36,933 cR5000. Fewer than 15% of
      the markers (472) could not be placed within any linkage group at a LOD score
      >or= 8. Linkage group order for each chromosome was determined by incorporation
      of markers previously assigned by FISH and by alignment with the bovine genome
      sequence assembly (Btau_4.0). CONCLUSION: We obtained radiation hybrid chromosome
      maps for the entire river buffalo genome based on cattle-derived markers. The
      alignments of our RH maps to the current bovine genome sequence assembly
      (Btau_4.0) indicate regions of possible rearrangements between the chromosomes of
      both species. The river buffalo represents an important agricultural species
      whose genetic improvement has lagged behind other species due to limited prior
      genomic characterization. We present the first-generation RH map which provides a
      more extensive resource for positional candidate cloning of genes associated with
      complex traits and also for large-scale physical mapping of the river buffalo
      genome.

PMID- 19108730
TI  - Smoking, environmental tobacco smoke, and risk of renal cell cancer: a population
      based case-control study.
AB  - BACKGROUND: Kidney and renal pelvis cancers account for 4% of all new cancer
      cases in the United States, among which 85% are renal cell carcinomas (RCC).
      While cigarette smoking is an established risk factor for RCC, little is known
      about the contribution of environmental tobacco smoke (ETS) to RCC incidence.
      This study assesses the role of smoking and ETS on RCC incidence using a
      population-based case-control design in Florida and Georgia. METHODS: Incident
      cases (n = 335) were identified from hospital records and the Florida cancer
      registry, and population controls (n = 337) frequency-matched by age (+/- 5
      years), gender, and race were identified through random-digit dialing. In-person
      interviews assessed smoking history and lifetime exposure to ETS at home, work,
      and public spaces. Home ETS was measured in both years and hours of exposure.
      Odds ratios and 95% confidence intervals were calculated using logistic
      regression, controlled for age, gender, race, and BMI. RESULTS: Cases were more
      likely to have smoked 20 or more pack-years, compared with never-smokers (OR:
      1.35, 95% CI: 0.93 - 1.95). A protective effect was found for smoking cessation,
      beginning with 11-20 years of cessation (OR: 0.39, 95% CI: 0.18-0.85) and ending
      with 51 or more years of cessation (OR: 0.11, 95% CI: 0.03-0.39) in comparison
      with those having quit for 1-10 years. Among never-smokers, cases were more
      likely to report home ETS exposure of greater than 20 years, compared with those
      never exposed to home ETS (OR: 2.18; 95% CI: 1.14-4.18). Home ETS associations
      were comparable when measured in lifetime hours of exposure, with cases more
      likely to report 30,000 or more hours of home ETS exposure (OR: 2.37; 95% CI:
      1.20-4.69). Highest quartiles of combined home/work ETS exposure among never
      smokers, especially with public ETS exposure, increased RCC risk by 2 to 4 times.
      CONCLUSION: These findings confirm known associations between smoking and RCC and
      establish a potential etiologic role for ETS, particularly in the home.
      Differences in methods of retrospective measurement of lifetime smoking and ETS
      exposure may contribute to discrepancies in measures of associations across
      studies, and should be addressed in future research.

PMID- 19108731
TI  - Impact of demographic factors on recognition of persons with depression and
      anxiety in primary care in Slovenia.
AB  - BACKGROUND: Research has repeatedly shown that family physicians fail to diagnose
      up to 70% of patients with common mental disorders. Objective of the study is to
      investigate associations between persons' gender, age and educational level and
      detection of depression and anxiety by their family physicians. METHODS: We
      compared the results of two independent observational studies that were performed
      at the same time on a representative sample of family medicine practice attendees
      in Slovenia. 10710 patients participated in Slovenian Cross-sectional survey and
      1118 patients participated in a first round of a cohort study (PREDICT-D study).
      Logistic regression was used to examine the effects of age, gender and
      educational level on detection of depression and anxiety. RESULTS: The prevalence
      of major depression and Other Anxiety Syndrome (OAS) amongst family practice
      attendees was low. The prevalence of Panic Syndrome (PS) was comparable to rates
      reported in the literature. A statistical model with merged data from both
      studies showed that it was over 15 times more likely for patients with ICD-10
      criteria depression to be detected in PREDICT-D study as in SCS survey. In
      PREDICT-D study it was more likely for people with higher education to be
      diagnosed with ICD-10 criteria depression than in SCS survey. CONCLUSION: People
      with higher levels of education should probably be interviewed in a more
      standardized way to be recognised as having depression by Slovenian family
      physicians. This finding requires further validation.

PMID- 19108732
TI  - Genetic characterization of the ABO blood group in Neandertals.
AB  - BACKGROUND: The high polymorphism rate in the human ABO blood group gene seems to
      be related to susceptibility to different pathogens. It has been estimated that
      all genetic variation underlying the human ABO alleles appeared along the human
      lineage, after the divergence from the chimpanzee lineage. A paleogenetic
      analysis of the ABO blood group gene in Neandertals allows us to directly test
      for the presence of the ABO alleles in these extinct humans. RESULTS: We have
      analysed two male Neandertals that were retrieved under controlled conditions at
      the El Sidron site in Asturias (Spain) and that appeared to be almost free of
      modern human DNA contamination. We find a human specific diagnostic deletion for
      blood group O (O01 haplotype) in both Neandertal individuals. CONCLUSION: These
      results suggest that the genetic change responsible for the O blood group in
      humans predates the human and Neandertal divergence. A potential selective event
      associated with the emergence of the O allele may have therefore occurred after
      humans separated from their common ancestor with chimpanzees and before the human
      Neandertal population divergence.

PMID- 19108733
TI  - Histone H1x is highly expressed in human neuroendocrine cells and tumours.
AB  - BACKGROUND: Histone H1x is a ubiquitously expressed member of the H1 histone
      family. H1 histones, also called linker histones, stabilize compact, higher order
      structures of chromatin. In addition to their role as structural proteins, they
      actively regulate gene expression and participate in chromatin-based processes
      like DNA replication and repair. The epigenetic contribution of H1 histones to
      these mechanisms makes it conceivable that they also take part in malignant
      transformation. METHODS: Based on results of a Blast data base search which
      revealed an accumulation of expressed sequence tags (ESTs) of H1x in libraries
      from neuroendocrine tumours (NETs), we evaluated the expression of H1x in NETs
      from lung and the gastrointestinal tract using immunohistochemisty. Relative
      protein and mRNA levels of H1x were analysed by Western blot analysis and
      quantitative real-time RT-PCR, respectively. Since several reports describe a
      change of the expression level of the replacement subtype H1.0 during
      tumourigenesis, the analysis of this subtype was included in this study. RESULTS:
      We found an increased expression of H1x but not of H1.0 in NET tissues in
      comparison to corresponding normal tissues. Even though the analysed NETs were
      heterogenous regarding their grade of malignancy, all except one showed a
      considerably higher protein amount of H1x compared with corresponding non
      neoplastic tissue. Furthermore, double-labelling of H1x and chromogranin A in
      sections of pancreas and small intestine revealed that H1x is highly expressed in
      neuroendocrine cells of these tissues. CONCLUSION: We conclude that the high
      expression of histone H1x in NETs is probably due to the abundance of this
      protein in the cells from which these tumours originate.

PMID- 19108734
TI  - The cancer translational research informatics platform.
AB  - BACKGROUND: Despite the pressing need for the creation of applications that
      facilitate the aggregation of clinical and molecular data, most current
      applications are proprietary and lack the necessary compliance with standards
      that would allow for cross-institutional data exchange. In line with its mission
      of accelerating research discoveries and improving patient outcomes by linking
      networks of researchers, physicians, and patients focused on cancer research,
      caBIG (cancer Biomedical Informatics Grid) has sponsored the creation of the
      caTRIP (Cancer Translational Research Informatics Platform) tool, with the
      purpose of aggregating clinical and molecular data in a repository that is user
      friendly, easily accessible, as well as compliant with regulatory requirements of
      privacy and security. RESULTS: caTRIP has been developed as an N-tier
      architecture, with three primary tiers: domain services, the distributed query
      engine, and the graphical user interface, primarily making use of the caGrid
      infrastructure to ensure compatibility with other tools currently developed by
      caBIG. The application interface was designed so that users can construct queries
      using either the Simple Interface via drop-down menus or the Advanced Interface
      for more sophisticated searching strategies to using drag-and-drop. Furthermore,
      the application addresses the security concerns of authentication, authorization,
      and delegation, as well as an automated honest broker service for deidentifying
      data. CONCLUSION: Currently being deployed at Duke University and a few other
      centers, we expect that caTRIP will make a significant contribution to further
      the development of translational research through the facilitation of its data
      exchange and storage processes.

PMID- 19108735
TI  - Movement control tests of the low back; evaluation of the difference between
      patients with low back pain and healthy controls.
AB  - BACKGROUND: To determine whether there is a difference between patients with low
      back pain and healthy controls in a test battery score for movement control of
      the lumbar spine. METHODS: This was a case control study, carried out in five
      outpatient physiotherapy practices in the German-speaking part of Switzerland.
      Twelve physiotherapists tested the ability of 210 subjects (108 patients with non
      specific low back pain and 102 control subjects without back pain) to control
      their movements in the lumbar spine using a set of six tests. We observed the
      number of positive tests out of six (mean, standard deviation and 95% confidence
      interval of the mean). The significance of the differences between the groups was
      calculated with Mann-Whitney U test and p was set on <0.05. The effect size (d)
      between the groups was calculated and d>0.8 was considered a large difference.
      RESULTS: On average, patients with low back pain had 2.21(95%CI 1.94-2.48)
      positive tests and the healthy controls 0.75 (95%CI 0.55-0.95). The effect size
      was d = 1.18 (p < 0.001). There was a significant difference between acute and
      chronic (p < 0.01), as well as between subacute and chronic patient groups (p <
      0.03), but not between acute and subacute patient groups (p > 0.7). CONCLUSION:
      This is the first study demonstrating a significant difference between patients
      with low back pain and subjects without back pain regarding their ability to
      actively control the movements of the low back. The effect size between patients
      with low back pain and healthy controls in movement control is large.

PMID- 19108736
TI  - Selecting interventions to promote fruit and vegetable consumption: from policy
      to action, a planning framework case study in Western Australia.
AB  - BACKGROUND: The Department of Health in Western Australia identified access to,
      and daily consumption of recommended amounts of fruit and vegetables, as priority
      health determinants. The numerous factors that influence supply and consumption
      of fruit and vegetables indicated that a comprehensive approach would be
      required.A government and non-government sector steering group was set up to
      select priority interventions using the National Public Health Partnership's
      Framework for Implementing Public Health Strategies. This structured framework
      was used for developing strategies to improve fruit and vegetable consumption and
      supply, and to identify implementation priorities.After one year a desktop audit
      of progress on framework interventions was undertaken. RESULTS: The structured
      framework led to a plan for defined actions, partners, costs, and performance
      indicators for strategies to improve fruit and vegetable consumption and supply.
      Lead agency custodians for management of the selected interventions were
      identified.After one year there was significant progress in the implementation of
      a number of the high-ranking interventions. The exception was interventions that
      provide the infrastructure support such as research and development capacity,
      information systems. CONCLUSION: A structured framework and stakeholder
      participation assisted in developing a fruit and vegetable implementation
      strategy. Engagement and commitment of influential and diverse stakeholders is
      needed, not just for program support, but particularly in the areas of food and
      nutrition policy development and providing the infrastructure support required.
      Further work is required to develop performance outcomes and cost effectiveness
      measures for many of the strategies that have been proposed to address portfolio
      objectives.

PMID- 19108737
TI  - Comparative evaluation of three PCR base diagnostic assays for the detection of
      pathogenic trypanosomes in cattle blood.
AB  - Currently, several PCR based diagnostic assays have been developed to improve
      the detection of pathogenic trypanosomes. These tests include use of species
      specific primers, single and nested PCRs' based on primers amplifying the
      Internal Transcribed Spacer (ITS) regions of ribosomal DNA. This study compares
      three PCR based diagnostic assays and assesses the agreement of these three
      asaays by screening 103 cattle blood samples randomly collected from trypanosome
      endemic areas in western Kenya. The nested ITS based PCR, the single ITS based
      PCR and the species specific based PCR detected 28.1%, 26.2% and 10.7% of the
      samples respectively as positive for trypanosome infection. Nested ITS and single
      ITS PCRs' picked 3.8% and 1.9% as mixed infections respectively. Cohen kappa
      statistic used to compare agreements beyond chance between the assays showed
      highest degree of agreement (0.6) between the two ITS based tests, and the lowest
      (0.2) between the nested PCR test and the species specific PCR. The single ITS
      and nested ITS based diagnostic assays detected higher numbers of positive cases,
      and reduced the number of PCR reactions per sample to one and two respectively,
      compared to the five PCR reactions carried out using the species specific
      primers. This significantly reduced the labour, time and the cost of carrying out
      PCR tests, indicating the superiority of the ITS multi-species detection
      techniques. Reliable epidemiological studies are a prerequisite to designing
      effective tsetse and trypanosomiasis control programs. The present study
      established the suitability of using ITS based PCR assays for large-scale
      epidemiological studies.

PMID- 19108738
TI  - Haptoglobin phenotype is not a predictor of recurrence free survival in high-risk
      primary breast cancer patients.
AB  - BACKGROUND: Better breast cancer prognostication may improve selection of
      patients for adjuvant therapy. We conducted a retrospective follow-up study in
      which we investigated sera of high-risk primary breast cancer patients, to search
      for proteins predictive of recurrence free survival. METHODS: Two sample sets of
      high-risk primary breast cancer patients participating in a randomised national
      trial investigating the effectiveness of high-dose chemotherapy were analysed.
      Sera in set I (n = 63) were analysed by surface enhanced laser desorption
      ionisation time-of-flight mass spectrometry (SELDI-TOF MS) for biomarker finding.
      Initial results were validated by analysis of sample set II (n = 371), using one
      dimensional gel-electrophoresis. RESULTS: In sample set I, the expression of a
      peak at mass-to-charge ratio 9198 (relative intensity <or= 20 or > 20),
      identified as haptoglobin (Hp) alpha-1 chain, was strongly associated with
      recurrence free survival (global Log-rank test; p = 0.0014). Haptoglobin is
      present in three distinct phenotypes (Hp 1-1, Hp 2-1, and Hp 2-2), of which only
      individuals with phenotype Hp 1-1 or Hp 2-1 express the haptoglobin alpha-1
      chain. As the expression of the haptoglobin alpha-1 chain, determined by SELDI
      TOF MS, corresponds to the phenotype, initial results were validated by
      haptoglobin phenotyping of the independent sample set II by native one
      dimensional gel-electrophoresis. With the Hp 1-1 phenotype as the reference
      category, the univariate hazard ratio for recurrence was 0.87 (95% CI: 0.56 -
      1.34, p = 0.5221) and 1.03 (95% CI: 0.65 - 1.64, p = 0.8966) for the Hp 2-1 and
      Hp 2-2 phenotypes, respectively, in sample set II. CONCLUSION: In contrast to our
      initial results, the haptoglobin phenotype was not identified as a predictor of
      recurrence free survival in high-risk primary breast cancer in our validation
      set. Our initial observation in the discovery set was probably the result of a
      type I error (i.e. false positive). This study illustrates the importance of
      validation in obtaining the true clinical applicability of a potential biomarker.

PMID- 19108739
TI  - Bipotential mouse embryonic liver (BMEL) cells spontaneously express Pdx1 and
      Ngn3 but do not undergo further pancreatic differentiation upon Hes1 down
      regulation.
AB  - BACKGROUND: Liver-to-pancreas conversion offers new possibilities for beta-cell
      engineering for type 1 diabetes therapy. Among conceivable sources of liver
      cells, we focused on BMEL cells. These untransformed mouse embryonic liver cells
      have been reproducibly isolated from different inbred mice strains and have the
      potential to differentiate into hepatocytes and cholangiocytes in vitro and in
      vivo. FINDINGS: Strikingly, we find here that adherent BMEL cells display
      functional similarities with multipotent pancreatic precursor cells, namely Pdx1
      and Ngn3 expression, and further express Hnf6 in floating aggregate culture.
      Hes1, a direct repressor of Ngn3 and pancreatic endocrine commitment, is
      expressed in adherent BMEL cells and decreases with time in aggregate culture.
      However, Hes1 decrease fails to initiate activation of late-stage pancreatic
      endocrine transcription factors. CONCLUSION: Here we report that BMEL cells
      present features of pancreatic endocrine progenitor cells. In the field of
      diabetes research, BMEL cells are of potential interest for the study of
      inductive signals critical for in vitro beta-cell maturation in-liver-to-pancreas
      conversion.

PMID- 19108740
TI  - Renal haemodynamic, microcirculatory, metabolic and histopathological responses
      to peritonitis-induced septic shock in pigs.
AB  - INTRODUCTION: Our understanding of septic acute kidney injury (AKI) remains
      incomplete. A fundamental step is the use of animal models designed to meet the
      criteria of human sepsis. Therefore, we dynamically assessed renal haemodynamic,
      microvascular and metabolic responses to, and ultrastructural sequelae of, sepsis
      in a porcine model of faecal peritonitis-induced progressive hyperdynamic sepsis.
      METHODS: In eight anaesthetised and mechanically ventilated pigs, faecal
      peritonitis was induced by inoculating autologous faeces. Six sham-operated
      animals served as time-matched controls. Noradrenaline was administered to
      maintain mean arterial pressure (MAP) greater than or equal to 65 mmHg. Before
      and at 12, 18 and 22 hours of peritonitis systemic haemodynamics, total renal
      (ultrasound Doppler) and cortex microvascular (laser Doppler) blood flow, oxygen
      transport and renal venous pressure, acid base balance and lactate/pyruvate
      ratios were measured. Postmortem histological analysis of kidney tissue was
      performed. RESULTS: All septic pigs developed hyperdynamic shock with AKI as
      evidenced by a 30% increase in plasma creatinine levels. Kidney blood flow
      remained well-preserved and renal vascular resistance did not change either.
      Renal perfusion pressure significantly decreased in the AKI group as a result of
      gradually increased renal venous pressure. In parallel with a significant
      decrease in renal cortex microvascular perfusion, progressive renal venous
      acidosis and an increase in lactate/pyruvate ratio developed, while renal oxygen
      consumption remained unchanged. Renal histology revealed only subtle changes
      without signs of acute tubular necrosis. CONCLUSION: The results of this
      experimental study argue against the concept of renal vasoconstriction and
      tubular necrosis as physiological and morphological substrates of early septic
      AKI. Renal venous congestion might be a hidden and clinically unrecognised
      contributor to the development of kidney dysfunction.

PMID- 19108741
TI  - Protocol of a randomized controlled trial of the effectiveness of physician
      education and activation versus two rehabilitation programs for the treatment of
      Whiplash-associated Disorders: The University Health Network Whiplash
      Intervention Trial.
AB  - BACKGROUND: Whiplash injuries are an important public health problem that is
      associated with significant disability and high health care utilization. Recent
      cohort studies suggest that physician care may be the most effective treatment
      for patients with whiplash-associated disorders. However, these findings have not
      been tested in a randomized controlled trial. The purpose of this study is to
      determine which of physician care or two rehabilitation programs of care is most
      effective in improving recovery of patients with recent whiplash associated
      disorders. METHODS AND DESIGN: We designed a pragmatic randomized clinical trial.
      A total of 444 participants (148 in each of three arms) who reside in Southern
      Ontario, Canada will be recruited from a large insurer. We will include
      individuals who are 18 years of age or older and who are diagnosed with Grade I
      or II Whiplash-associated Disorders. Participants will be randomized to physician
      based education and activation or one of two rehabilitation programs of care
      currently in use in Ontario. Our primary outcome, self-rated global recovery and
      all secondary outcomes (neck pain intensity, whiplash disability, health-related
      quality of life, depressive symptomatology and satisfaction with care) will be
      measured at baseline by a trial coordinator and at 6 weeks, 3, 6, 9 and 12 months
      follow-up by an interviewer who is blind to the participants' baseline
      characteristics and treatment allocation. We will also collect information on
      general health status, other injuries, comorbidities, expectation of recovery,
      work status, pain coping, legal representation, and co-interventions. The primary
      intention-to-treat analysis will compare time to recovery between the three
      interventions. This trial will have 90% power at an alpha of 0.05 to detect a 20%
      difference in the rate of perceived recovery at one year. Secondary analyses will
      compare the health outcomes, rate of recurrence and the rate of adverse events
      between intervention groups. CONCLUSION: The results of this study will provide
      the public, clinicians and policy makers much needed evidence on the
      effectiveness of common approaches used to manage whiplash-associated disorders.
      TRIAL REGISTRATION: ClinicalTrials.gov identifier NCT00546806.

PMID- 19108742
TI  - [(18)F]Fluoroethyltyrosine- positron emission tomography-guided radiotherapy for
      high-grade glioma.
AB  - BACKGROUND: To compare morphological gross tumor volumes (GTVs), defined as pre-
      and postoperative gadolinium enhancement on T1-weighted magnetic resonance
      imaging to biological tumor volumes (BTVs), defined by the uptake of (18)F
      fluoroethyltyrosine (FET) for the radiotherapy planning of high-grade glioma,
      using a dedicated positron emission tomography (PET)-CT scanner equipped with
      three triangulation lasers for patient positioning. METHODS: Nineteen patients
      with malignant glioma were included into a prospective protocol using FET PET-CT
      for radiotherapy planning. To be eligible, patients had to present with residual
      disease after surgery. Planning was performed using the clinical target volume
      (CTV = GTV union or logical sum BTV) and planning target volume (PTV = CTV + 20
      mm). First, the interrater reliability for BTV delineation was assessed among
      three observers. Second, the BTV and GTV were quantified and compared. Finally,
      the geometrical relationships between GTV and BTV were assessed. RESULTS:
      Interrater agreement for BTV delineation was excellent (intraclass correlation
      coefficient 0.9). Although, BTVs and GTVs were not significantly different (p =
      0.9), CTVs (mean 57.8 +/- 30.4 cm(3)) were significantly larger than BTVs (mean
      42.1 +/- 24.4 cm(3); p < 0.01) or GTVs (mean 38.7 +/- 25.7 cm(3); p < 0.01). In
      13 (68%) and 6 (32%) of 19 patients, FET uptake extended >or= 10 and 20 mm from
      the margin of the gadolinium enhancement. CONCLUSION: Using FET, the interrater
      reliability had excellent agreement for BTV delineation. With FET PET-CT
      planning, the size and geometrical location of GTVs and BTVs differed in a
      majority of patients.

PMID- 19108743
TI  - The GC-heterogeneity of teleost fishes.
AB  - BACKGROUND: One of the most striking features of mammalian and birds chromosomes
      is the variation in the guanine-cytosine (GC) content that occurs over scales of
      hundreds of kilobases to megabases; this is known as the "isochore" structure.
      Among other vertebrates the presence of isochores depends upon the taxon;
      isochore are clearly present in Crocodiles and turtles but fish genome seems very
      homogeneous on GC content. This has suggested a unique isochore origin after the
      divergence between Sarcopterygii and Actinopterygii, but before that between
      Sauropsida and mammals. However during more than 30 years of analysis, isochore
      characteristics have been studied and many important biological properties have
      been associated with the isochore structure of human genomes. For instance, the
      genes are more compact and their density is highest in GC rich isochores.
      RESULTS: This paper shows in teleost fish genomes the existence of "GC
      segmentation" sharing some of the characteristics of isochores although teleost
      fish genomes presenting a particular homogeneity in CG content. The entire
      genomes of T nigroviridis and D rerio are now available, and this has made it
      possible to check whether a mosaic structure associated with isochore properties
      can be found in these fishes. In this study, hidden Markov models were trained on
      fish genes (T nigroviridis and D rerio) which were classified by using the
      isochore class of their human orthologous. A clear segmentation of these genomes
      was detected. CONCLUSION: The GC content is an excellent indicator of isochores
      in heterogeneous genomes as mammals. The segmentation we obtained were well
      correlated with GC content and other properties associated to GC content such as
      gene density, the number of exons per gene and the length of introns. Therefore,
      the GC content is the main property that allows the detection of isochore but
      more biological properties have to be taken into account. This method allows
      detecting isochores in homogeneous genomes.

PMID- 19108744
TI  - Splenic rupture, secondary to G-CSF use for chemotherapy induced neutropenia: a
      case report and review of literature.
AB  - INTRODUCTION: Chemotherapy Induced neutropenia is a frequent and serious
      complication of cytotoxic cancer treatment.Granulocyte colony stimulating factors
      (G-CSF) are frequently used to counter neutropenia, attempt rapid recovery of
      patients and allow for continuation of treatment without compromise on dose,
      especially in curative malignancies. Generally regarded as safe, G-CSF use has
      been very rarely reported to have resulted in serious side effects, such as,
      splenic rupture. CASE PRESENTATION: We are reporting a case of a twenty years old
      man, who was being treated for T cell acute lymphoblastic leukemia and received
      colony stimulating factors for treatment of severe neutropenia and suffered from
      splenic rupture, He was treated with splenectomy. CONCLUSION: Although extremely
      rare, splenic rupture can be a serious and sometimes life threatening
      complication of high dose colony stimulating factors therapy.

PMID- 19108745
TI  - A comprehensive collection of experimentally validated primers for Polymerase
      Chain Reaction quantitation of murine transcript abundance.
AB  - BACKGROUND: Quantitative polymerase chain reaction (QPCR) is a widely applied
      analytical method for the accurate determination of transcript abundance. Primers
      for QPCR have been designed on a genomic scale but non-specific amplification of
      non-target genes has frequently been a problem. Although several online databases
      have been created for the storage and retrieval of experimentally validated
      primers, only a few thousand primer pairs are currently present in existing
      databases and the primers are not designed for use under a common PCR thermal
      profile. RESULTS: We previously reported the implementation of an algorithm to
      predict PCR primers for most known human and mouse genes. We now report the use
      of that resource to identify 17483 pairs of primers that have been experimentally
      verified to amplify unique sequences corresponding to distinct murine
      transcripts. The primer pairs have been validated by gel electrophoresis, DNA
      sequence analysis and thermal denaturation profile. In addition to the validation
      studies, we have determined the uniformity of amplification using the primers and
      the technical reproducibility of the QPCR reaction using the popular and
      inexpensive SYBR Green I detection method. CONCLUSION: We have identified an
      experimentally validated collection of murine primer pairs for PCR and QPCR which
      can be used under a common PCR thermal profile, allowing the evaluation of
      transcript abundance of a large number of genes in parallel. This feature is
      increasingly attractive for confirming and/or making more precise data trends
      observed from experiments performed with DNA microarrays.

PMID- 19108747
TI  - Metabolic pathway alignment between species using a comprehensive and flexible
      similarity measure.
AB  - BACKGROUND: Comparative analysis of metabolic networks in multiple species yields
      important information on their evolution, and has great practical value in
      metabolic engineering, human disease analysis, drug design etc. In this work, we
      aim to systematically search for conserved pathways in two species, quantify
      their similarities, and focus on the variations between them. RESULTS: We present
      an efficient framework, Metabolic Pathway Alignment and Scoring (M-PAS), for
      identifying and ranking conserved metabolic pathways. M-PAS aligns all reactions
      in entire metabolic networks of two species and assembles them into pathways,
      taking mismatches, gaps and crossovers into account. It uses a comprehensive
      scoring function, which quantifies pathway similarity such that we can focus on
      different pathways given different biological motivations. Using M-PAS, we
      detected 1198 length-four pathways fully conserved between Saccharomyces
      cerevisiae and Escherichia coli, and also revealed 1399 cases of a species using
      a unique route in otherwise highly conserved pathways. CONCLUSION: Our method
      efficiently automates the process of exploring reaction arrangement
      possibilities, both between species and within species, to find conserved
      pathways. We not only reconstruct conventional pathways such as those found in
      KEGG, but also discover new pathway possibilities. Our results can help to
      generate hypotheses on missing reactions and manifest differences in highly
      conserved pathways, which is useful for biology and life science applications.

PMID- 19108746
TI  - Altered ATP release and metabolism in dorsal root ganglia of neuropathic rats.
AB  - BACKGROUND: Adenosine 5'-triphosphate (ATP) has a ubiquitous role in metabolism
      and a major role in pain responses after tissue injury. We investigated the
      changes in basal and KCl-evoked ATP release from rat dorsal root ganglia (DRG)
      after peripheral neuropathy induction by unilateral sciatic nerve entrapment
      (SNE). RESULTS: After SNE, rats develop long-lasting decreases in ipsilateral
      hindpaw withdrawal thresholds to mechanical and thermal stimulation. At 15-21
      days after neuropathy induction, excised ipsilateral L4-L5 DRG display
      significantly elevated basal extracellular ATP levels compared to contralateral
      or control (naive) DRG. However, KCl-evoked ATP release is no longer observed in
      ipsilateral DRG. We hypothesized that the differential SNE effects on basal and
      evoked ATP release could result from the conversion of extracellular ATP to
      adenosine with subsequent activation of adenosine A1 receptors (A1Rs) on DRG
      neurons. Adding the selective A1R agonist, 2-chloro-N(6)-cyclopentyladenosine
      (100 nM) significantly decreased basal and evoked ATP release in DRG from naive
      rats, indicating functional A1R activation. In DRG ipsilateral to SNE, adding a
      selective A1R antagonist, 8-cyclopentyl-1,3-dipropylxanthine (30 nM), further
      increased basal ATP levels and relieved the blockade of KCl-evoked ATP release
      suggesting that increased A1R activation attenuates evoked ATP release in neurons
      ipsilateral to SNE. To determine if altered ATP release was a consequence of
      altered DRG metabolism we compared O(2) consumption between control and
      neuropathic DRG. DRG ipsilateral to SNE consumed O(2) at a higher rate than
      control or contralateral DRG. CONCLUSION: These data suggest that peripheral
      nerve entrapment increases DRG metabolism and ATP release, which in turn is
      modulated by increased A1R activation.

PMID- 19108748
TI  - Cardiac tamponade, an unusual and fatal complication of esophagus dilatation for
      benign stenosis: a case report.
AB  - INTRODUCTION: We present a patient with a fatal late esophago-pericardial fistula
      three months after dilatation for benign oesophagus stenosis CASE PRESENTATION: A
      71-year-old caucasian male with a known benign esophagus stenosis was referred to
      the ICU. On arrival an asystole developed which proved to be due to a large
      pericardial effusion. Pericardial fluids were drained, but the patients'
      condition worsened and he died due to multiple organ failure. Postmortum
      investigation revealed an esophago-pericardial fistula. CONCLUSION: Causes of an
      acute tamponade should also be sought in semirecent events, such as manipulation
      to the oesophagus months before the acute critical illness.

PMID- 19108749
TI  - Does mood really influence comparative optimism? Tracking an elusive effect.
AB  - Methodological limitations call into question prior evidence that positive moods
      are associated with greater comparative optimism. Experiments 1-4 tested if mood
      affects comparative optimism using a mood manipulation that minimized
      experimenter demand. While the procedure was successful in inducing mood, we
      found no evidence for a mood effect on comparative optimism. The absence of a
      mood effect was not due to participants correcting their judgments in response to
      a presumed mood bias (Experiments 2, 3 and 4) or to participants proactively
      regulating their mood (Experiments 3 and 4). Experiment 5 compared the mood
      manipulation of Experiments 1-4 with an autobiographical recall procedure.
      Although the two methods were equally effective in inducing mood, only
      autobiographical recall influenced participants' comparative optimism. Study 6
      provides preliminary evidence that experimenter demand may be responsible for the
      effects of autobiographical recall on comparative judgments.

PMID- 19108750
TI  - The role of attributions in the process of overcoming shame: A qualitative
      analysis.
AB  - OBJECTIVES: While attributions have been found to play an important role in the
      experience of shame, little is currently known about attributions that occur as
      part of shame reparation. This exploratory study investigated the attributions
      associated with recovery from shame, based on the perspectives of participants.
      DESIGN: Grounded theory was used in data collection and analysis. This approach
      has been used extensively for developing understandings of how people construct
      meaning, interpret events, and act on the basis of their beliefs and
      interpretations. METHODS: The participants were nine women and four men between
      the ages of 24 and 70. Data came from interviews in which the participants
      recalled a distressing shame experience and described how they recovered.
      Emphasis was on the participants' subjective perspectives, meanings, and
      interpretations. RESULTS: Shame involved global and stable dispositional
      attributions where the entire self was regarded as flawed and unattractive, and
      participants perceived themselves as powerless to change an unwanted identity.
      Internal causal attributions and self-blame were present in most but not all
      shame experiences. Recovery involved a movement towards specific and unstable
      attributions that enhanced self-concept and maximized a sense of power and
      control over the future. Shared and external factors that contributed to the
      event were also identified. CONCLUSIONS: When applied to psychotherapy for shame
      related distress, these findings point to the importance of exploring clients'
      attributions related to specific shame events and using interventions that
      promote attributional change. Directions for further research are discussed.

PMID- 19108751
TI  - Macrophage-secreted factors enhance the in vitro expansion of DMD muscle
      precursor cells while preserving their myogenic potential.
AB  - OBJECTIVE: Autologous cell transplantation has been proposed as a possible
      therapeutic approach for Duchenne dystrophy. In this approach, patients' muscle
      precursor cells (mpcs) obtained from muscle biopsies would be expanded ex vivo,
      genetically modified to restore dystrophin expression and then reimplanted in the
      original donor. Such strategy would have the advantage of bypassing the immune
      response problem, but on the other hand, it would require a large number of cells
      because of the poor viability and mobility of transplanted myoblasts. Besides,
      extensive multiplication of mpcs is difficult and can affect their myogenic
      ability. Given the key role of inflammation in muscle regeneration, we set out to
      verify if factors secreted by inflammatory cells could be used to improve in
      vitro expansion of DMD-mpcs. METHODS: We have previously shown that a murine
      macrophage conditioned medium (mMCM) could increase the in vitro proliferation
      rate of rat and mouse mpcs. Here we tested the effect of mMCM on cultures of
      human, dystrophin-deficient mpcs (DMD-mpcs). RESULTS: In the presence of mMCM,
      DMD-mpcs displayed an increased proliferation rate, while at the same time,
      maintaining their myogenicity after many in vitro passages. Expanded cells were
      also injected in muscles of immuno-deficient mice, showing that they were also
      able to participate in muscle regeneration within recipient muscles. DISCUSSION:
      Using macrophagic factors, we were able to increase the amount of DMD-mpcs
      obtainable after 38 days of culture by >7 x 10(3)-fold. These findings indicate
      that macrophagic factors hold great potential for future use in cell
      transplantation protocol.

PMID- 19108752
TI  - Hydrocephalus in posterior fossa lesions: ventriculostomy and permanent shunt
      rates by diagnosis.
AB  - OBJECTIVES: The rate of ventriculostomy for acute hydrocephalus and progression
      to shunt-dependent chronic hydrocephalus in patients with posterior fossa lesions
      are not well known. METHODS: We retrospectively reviewed 104 consecutive cases
      with posterior fossa lesions on admission to the University of Illinois Hospital
      from June 2002 to December 2005. We recorded the rate of ventriculostomy and
      permanent ventricular shunting, which were compared among etiologic groups, using
      chi-squared and Fisher's exact tests. RESULTS: Overall, 35 patients had
      ventriculostomy for acute hydrocephalus and 16 had permanent shunting for shunt
      dependent chronic hydrocephalus. Of those with primary posterior fossa
      intracranial hemorrhage (ICH) (42 cases), 19 (45%) required ventriculostomy, with
      five (26%) requiring subsequent permanent shunting; 13 patients had hematoma
      evacuation, with two having permanent shunting. Of those with cerebellar
      infarction (14 cases), four (29%) required ventriculostomy and one (25%) had a
      permanent shunt; two had a decompressive craniectomy. Of those with neoplasms (43
      cases, 33 surgically resected), ten (23%) required ventriculostomy and nine (21%)
      required permanent shunting. In addition, two of the three cases with infectious
      processes required ventriculostomy and one required a permanent shunt. In
      hospital mortality was 21% (9/42 cases) for patients with ICH, 14% (2/14 cases)
      for patients with infarction and 0% for all others. DISCUSSION: Acute primary
      posterior fossa hemorrhage has the highest rate of ventriculostomy for acute
      hydrocephalus and highest inpatient mortality but a surprisingly low rate of
      permanent shunt-dependency. When hydrocephalus was caused by a neoplasm, there
      was a higher rate of permanent shunt placement.

PMID- 19108753
TI  - Long-term follow-up of endovascular coil embolization for cerebral aneurysms
      using three-dimensional time-of-flight magnetic resonance angiography.
AB  - OBJECTIVES: As endovascular treatment becomes more prevalent, aneurysm recurrence
      from neck remnants, recanalization, incomplete obliteration and bleeding remain
      major concerns. In the current analysis, we attempted to identify factors related
      to disease progression and clinical outcome in patients treated with coil
      embolization. METHODS: This study included 58 patients who underwent endovascular
      coil embolization for treatment of intracranial aneurysm. The result of
      embolization was evaluated with three-dimensional time-of-flight magnetic
      resonance angiography (TOF MRA) and classified as a complete occlusion, a
      residual neck (minor, central and marginal types), a residual dome (central and
      marginal types). Patients were followed up clinically and radiologically.
      Statistical analyses were performed to establish factors that influenced the
      occurrence of adverse events such as recurrence of aneurysm. RESULTS: Overall,
      the complete occlusion rate was 18.8%, the occurrence of a residual neck was
      67.2%, and the residual dome rate was 14.1%. The mean clinical follow-up was 31.2
      months. Recurrences were found in 18 aneurysms, and major recurrences were
      retreated with coiling or surgery. The post-treatment study revealed that the
      marginal-type aneurysm filling has a significant impact on outcome. Thus,
      perianeurysmal edema was correlated with recurrence of the aneurysm. CONCLUSIONS:
      Three-dimensional TOF MRA was a sensitive tool for visualizing residual filling
      of embolized aneurysm and is useful for long-term follow-up of patients.

PMID- 19108754
TI  - Early post-ischemic hyperemia on transcranial cerebral oxygen saturation
      monitoring in carotid endarterectomy is associated with severity of cerebral
      ischemic insult during carotid artery clamping.
AB  - BACKGROUND AND OBJECTIVE: In animal models, the magnitude of early post-ischemic
      hyperemia tends to correlate with the duration and intensity of prior ischemic
      insult. The aim of this study was to determine whether early post-ischemic
      hyperemia in human brain during carotid endarterectomy (CEA) is associated with
      the severity of cerebral ischemic insult during clamping of the internal carotid
      artery (ICA). METHODS: Transcranial cerebral oxygen saturation using near
      infrared spectroscopy was monitored intraoperatively in 171 patients undergoing
      CEA for ipsilateral ICA stenosis (>70%) to assess the intensity of cerebral
      hemispheric ischemia during ICA clamping and the magnitude of early post-ischemic
      hyperemia after ICA declamping. RESULTS: Early post-ischemic hyperemia peaked
      within 3 minutes after ICA declamping and resolved at 20 minutes after ICA
      declamping. A significant correlation was observed between the magnitude of early
      post-ischemic hyperemia and the intensity of cerebral ischemia (r=0.697;
      p<0.0001). Eight patients recovered from anesthesia with a new minor neurological
      deficit on the side contralateral to the CEA (4.7%). Analysis by receiver
      operating characteristics (ROC) curve was used to estimate the ability to
      discriminate between patients with and without post-operative development of new
      neurological deficits. Area under the ROC curve was significantly greater when
      analysing the magnitude of early post-ischemic hyperemia (1.00; 95% CI: 0.99
      1.00) when compared with the intensity of cerebral ischemia (0.93; 95% CI: 0.89
      0.98) (p<0.01). CONCLUSION: Early post-ischemic hyperemia in CEA is correlated
      with the severity of cerebral ischemic insult during clamping of the ICA.

PMID- 19108755
TI  - Herb-partition moxibustion relieves chronic visceral hyperalgesia and 5-HT
      concentration in colon mucosa of rats.
AB  - OBJECTIVE: The aim of this study was to evaluate the effect of herb-partition
      moxibustion on rectal sensory thresholds and to analyse possible mechanism of
      herb-partition moxibustion in treating chronic visceral hypersensitivity rats.
      METHODS: Herb-partition moxibustion was administered to chronic visceral
      hypersensitivity rats for 7 days (once daily). Two moxa cylinders were used for
      each point in one treatment. Chronic visceral hypersensitivity rats without herb
      partition moxibustion and normal rats were chosen as the control groups.
      Detection of abdominal withdrawal reflex was performed during 30-90 minutes after
      the first treatment. After seven treatments, a segment of distal colon (5 cm in
      length) was harvested, and 5-hydroxytryptamine concentration in the colon tissue
      was detected by enzyme-linked immunosorbent assay. RESULTS: Herb-partition
      moxibustion significantly depressed abnormally increased AWR scores from the
      rectus abdominis in response to colorectal distention stimulation at strengths of
      40 and 60 mmHg. Herb-partition moxibustion decreased 5-hydroxytryptamine
      concentration in colon tissue of chronic visceral hypersensitivity rats.
      CONCLUSION: Herb-partition moxibustion enhances the pain threshold of chronic
      visceral hypersensitivity rats and restores normal sensitivity by 5
      hydroxytryptamine concentration decreased in the colon tissue. However, whether
      herb-partition moxibustion could enhance the pain threshold of IBS patients or
      not is not concluded in this study because of only small sample rats experiment.

PMID- 19108756
TI  - Response of neural precursor cells in the brain of Parkinson's disease mouse
      model after LIF administration.
AB  - OBJECTIVE: To access the response of endogenous neural precursor cells (NPCs) in
      the area of substantia nigra (SN) in the mouse model of Parkinson's disease (PD).
      To evaluate whether leukemia inhibitory factor (LIF) can up-regulate the
      expression of NPCs and their fate in differentiation. METHODS: NPCs were measured
      and the number and density were estimated using the confocal counting system in
      normal control (CON), normal control LIF treated (CON + LIF), PD (PD) and LIF
      treated PD (PD + LIF) mice. RESULTS: The PD + LIF group showed a statistically
      significant improvement in the number and density of NPCs compared with PD group,
      and NPCs are rarely seen in CON and CON + LIF groups. CONCLUSION: LIF may be a
      useful treatment for PD by up-regulating the re-expression of NPCs, which may
      represent the neuroprotection mechanism of LIF.

PMID- 19108757
TI  - Evidence-based pharmacotherapy for cerebral vasospasm.
AB  - INTRODUCTION: The vast amount of literature on the pharmaceutical treatment of
      cerebral vasospasm after aneurysmal subarachnoid hemorrhage remains daunting.
      Optimal treatment regimens for patients can be obscured by studies not
      statistically powered to draw evidenced-based conclusions. METHODS: In this
      chapter, we reviewed the English literature using the National Library of
      Medicine for studies regarding pharmacotherapies for the treatment of cerebral
      vasospasm. These studies were then categorized according to the US Preventative
      Services Task Force ranking system for evidence based medicine and reviewed each
      pharmacotherapy for its efficacy in the treatment of cerebral vasospasm. RESULTS:
      Nimodipine (Nimotop), HMG Co-A reductase inhibitor (statins) and enoxaparin
      (Lovenox) were the only drugs with level-1 evidence available for the treatment
      of vasospasm from aneurysmal subarachnoid hemorrhage as defined by the US
      Preventative Services Task Force. CONCLUSION: As the understanding of the
      pathophysiological mechanisms of vasospasm after aneurysmal subarachnoid
      hemorrhage evolves in the basic science laboratory, novel medications are being
      trialed in humans. However, significantly more work must be carried out in this
      area before we have an effective medical treatment that can prevent or reverse
      the devastating events of cerebral vasospasm.

PMID- 19108759
TI  - Experimental models of subarachnoid hemorrhage for studies of cerebral vasospasm.
AB  - OBJECTIVE: A multitude of subarachnoid hemorrhage (SAH) models have been
      described but only several of them are still in use. All models to a different
      degree helped in understanding of pathophysiology of cerebral vasospasm after
      SAH. Their advantages and drawbacks have been reviewed in this paper. Since 2000,
      when the last review on cerebral vasospasm in animal models was written, new
      animal models of SAH were introduced and our knowledge about pathophysiology of
      CVS improved. The aim of present review was to update the information about well
      established and newly implemented models of vasospasm after SAH. MATERIALS AND
      METHODS: The MEDLINE searches were carried out using keywords that included
      'subarachnoid hemorrhage', 'animal', 'model', as well as names of animal species
      such as 'rats', 'dogs', 'mice', 'rabbits', 'pigs' or animal groups, e.g. 'non
      human primates'. Owing to a limited volume, only models of SAH in vivo were
      included in our review. RESULTS: We identified 53 original models of SAH in
      considered groups of animals. For the past several years, use of rats and mice
      became increasingly common in vasospasm studies due to advancements of imaging
      techniques, new approaches in vessel morphometry and reduced costs related to
      small animals. However, dog model of SAH is still considered superior for
      vasospasm studies as the ability of murine models to model human vasospasm is
      disputed. CONCLUSION: Testing new concepts of vasospasm etiology will require re
      evaluation of in vivo models of CVS. The updated knowledge about their advantages
      and limitations is necessary for effective design in future studies of cerebral
      vasospasm after SAH.

PMID- 19108758
TI  - Effects of morphine-dependent and withdrawal on activation of the distal
      cerebrospinal fluid contacting neurons' phosphorylation CREB in rat brain.
AB  - OBJECTIVE: To investigate the changes of pCREB protein expression in the distal
      cerebrospinal fluid contacting neurons induced by chronic morphine dependence and
      withdrawal. METHODS: Twenty-four Sprague-Dawley rats of both genders were
      randomly divided into three groups (n=8 each): control (Group I); chronic
      morphine dependence (Group II); chronic morphine abstinence (Group III). Chronic
      morphine dependence was induced by increasing doses of morphine, starting from 5
      to 260 mg/kg/day in 12 days. The animals were killed 24 hours later. We evaluated
      morphine dependence by measuring the behavioral expression of morphine withdrawal
      and pCREB double labeled neuron recordings of dorsal raphe nucleus. The CB
      HRP/pCREB double labeling method was used to observe the expression of pCREB in
      the distal cerebrospinal fluid contacting neurons. RESULTS: The results showed
      the number of double labeled neuron of distal cerebrospinal fluid contacting
      neuron in dorsal raphe nucleus with up-regulated expression. CONCLUSION: Morphine
      dependent and withdrawal can activate the distal cerebrospinal fluid contacting
      neurons phosphorylation CREB in rat brain. The cerebrospinal fluid contacting
      neuron is related to morphine withdrawal and dependence rats.

PMID- 19108760
TI  - Thrombin up-regulates vascular endothelial growth factor in experimental gliomas.
AB  - OBJECTIVE: Vascular endothelial growth factor is a potent stimulator of
      angiogenesis; activation of hypoxia inducible factor-1alpha and p44/42 mitogen
      activated protein kinase pathways has been associated with vascular endothelial
      growth factor production. The present study examined if thrombin modulates
      vascular endothelial growth factor levels in gliomas via hypoxia inducible factor
      1alpha and p44/42 mitogen-activated protein kinase pathways. METHODS: This study
      was divided into two parts: (1) adult male Fischer 344 rats had an intracaudatal
      implantation of C6 glioma cells. Rats were killed 6, 9 and 12 days later for
      Western blotting and immunohistochemistry. Hypoxia inducible factor-1alpha
      messenger ribonucleic acid was also determined; (2) cultured C6 cells were
      treated with vehicle, thrombin, thrombin plus YC-1, an inhibitor of hypoxia
      inducible factor-1alpha, or thrombin plus PD098059, an inhibitor of p44/42
      mitogen-activated protein kinases. Cell culture medium was collected for vascular
      endothelial growth factor measurement using an enzyme-linked immunosorbent assay
      kit. RESULTS: In vivo, immunoreactivities for thrombin, vascular endothelial
      growth factor, hypoxia inducible factor-1alpha and activated p44/42 mitogen
      activated protein kinases were detected in C6 gliomas. Thrombin immunoreactivity
      was co-localized with that of vascular endothelial growth factor, hypoxia
      inducible factor-1alpha or activated p44/42 mitogen-activated protein kinases. A
      time course showed that activated p44/42 mitogen-activated protein kinases and
      vascular endothelial growth factor protein levels increased in gliomas with time.
      Hypoxia inducible factor-1alpha protein levels were higher in C6 gliomas than
      those in the contralateral brain tissue. In vitro, thrombin exposure increased
      the levels of vascular endothelial growth factor, hypoxia inducible factor-1alpha
      and activated p44/42 mitogen-activated protein kinases in C6 cells. Thrombin
      induced vascular endothelial growth factor up-regulation was blocked by YC-1 and
      PD098059. DISCUSSION: Thrombin activates hypoxia inducible factor-1alpha and
      p44/42 mitogen-activated protein kinase pathways, and up-regulates vascular
      endothelial growth factor in gliomas. Inhibiting hypoxia inducible factor-1alpha
      and p44/42 mitogen-activated protein kinase pathways reduces the thrombin-induced
      up-regulation of vascular endothelial growth factor. These results suggest
      thrombin can increase vascular endothelial growth factor levels via activating
      hypoxia inducible factor-1alpha and p44/42 mitogen-activated protein kinase
      pathways in gliomas.

PMID- 19108761
TI  - Sydney Brenner's Loose Ends and False Starts.

PMID- 19108762
TI  - Ctenophores.

PMID- 19108763
TI  - The evolution of haploidy and diploidy.

PMID- 19108764
TI  - Honeybee buzz attenuates plant damage by caterpillars.

PMID- 19108765
TI  - Shade coffee farms promote genetic diversity of native trees.

PMID- 19108766
TI  - Intact navigation skills after bilateral loss of striate cortex.

PMID- 19108767
TI  - Symmetry breaking: scaffold plays matchmaker for polarity signaling proteins.
AB  - Many cell types can spontaneously polarize even in the absence of specific
      positional cues. In budding yeast, this symmetry-breaking polarization depends on
      a scaffold protein called Bem1p. A recent study defines Bem1p's molecular
      function during symmetry breaking.

PMID- 19108768
TI  - Convergent evolution: raising a family from the dead.
AB  - New molecular evidence shows that Hawaiian honeyeaters did not evolve from the
      similar looking Australasian honeyeaters, but instead represent a striking case
      of convergent evolution. These now extinct birds form their own family,
      representing the only complete extinction of an entire avian family in modern
      times.

PMID- 19108769
TI  - Perceptual learning: complete transfer across retinal locations.
AB  - A newly developed 'double training' technique demonstrates that practice
      dependent improvement in the discrimination of basic visual features will
      transfer to a location that has been trained with a different discrimination.

PMID- 19108770
TI  - Gene expression: dialing up the frequency.
AB  - Cells often respond to external signals by altering their gene expression. The
      external signaling information is transduced and typically encoded in
      concentrations of relevant transcription factors. A recent study demonstrates
      that, by encoding this information in the frequency with which genes 'see' a
      transcription factor, the expression of hundreds of genes can be modulated in a
      linearly proportional manner.

PMID- 19108771
TI  - Group decisions: how (not) to choose a restaurant with friends.
AB  - Subordinate baboons voluntarily follow the dominant group member to foraging
      patches where they themselves starve. One-sided preservation of social ties seems
      to prevail over fair decision sharing, contradicting recent theory.

PMID- 19108772
TI  - Giant proteins: sensing tension with titin kinase.
AB  - Recent studies at the single-molecule level show how signaling from the giant
      protein titin can be triggered by direct mechanical activation of its kinase
      domain.

PMID- 19108773
TI  - Speech production: how does a word feel?
AB  - Given the importance of auditory feedback in vocal production, how can deaf
      individuals produce intelligible speech? A new study suggests that somatosensory
      feedback is the answer and, more generally, offers intriguing insights into the
      action-oriented nature of sensory representations in the brain.

PMID- 19108774
TI  - Skotomorphogenesis: the dark side of light signalling.
AB  - The ability to switch from skotomorphogenic to photomorphogenic development is
      essential for seedling survival. Central to this mechanism are the phytochrome
      interacting factors that are important for maintaining the skotomorphogenic state
      and regulating the switch to photomorphogenesis.

PMID- 19108775
TI  - Spindle assembly: kinesin-5 is in control.
AB  - Kinesin-5 is essential in many species for the formation of a bipolar spindle.
      Although bipolar tetramers were known to crossbridge pairs of microtubules, the
      mechanism for organizing spindles was unclear. However, new experiments have
      revealed unique properties of kinesin-5, including some associated with the tail
      domain, that provide clues as to how spindles are assembled.

PMID- 19108776
TI  - A tip-localized RhoGAP controls cell polarity by globally inhibiting Rho GTPase
      at the cell apex.
AB  - BACKGROUND: Highly elongated eukaryotic cells (e.g., neuronal axons, fungal
      hyphae, and pollen tubes) are generated through continuous apically restricted
      growth (tip growth), which universally requires tip-localized Rho GTPases. We
      used the oscillating pollen tube as a model system to determine the function and
      regulation of Rho GTPases in tip growth. Our previous work showed that the
      spatiotemporal dynamics of the apical cap of the activated Rho-like GTPase from
      Plant 1 (ROP1) are critical for tip growth in pollen tubes. However, the
      underlying mechanism for the generation and maintenance of this dynamic apical
      cap is poorly understood. RESULTS: A screen for mutations that enhance ROP1
      overexpression-induced depolarization of pollen-tube growth identified REN1 (ROP1
      enhancer 1) in Arabidopsis, whose null mutations turn elongated pollen tubes into
      bulbous cells. REN1 encodes a novel Rho GTPase-activating protein (RhoGAP)
      required for restricting the ROP1 activity to the pollen-tube tip. REN1 was
      localized to exocytic vesicles accumulated in the pollen-tube apex, as well as to
      the apical plasma membrane at the site of ROP1 activation. The apical
      localization of REN1 and its function in controlling growth polarity was
      compromised by disruption of ROP1-dependent F-actin and vesicular trafficking,
      which indicates that REN1 targeting and function is regulated by ROP1 downstream
      signaling. CONCLUSIONS: Our findings suggest that the REN1 RhoGAP controls a
      negative-feedback-based global inhibition of ROP1. This function provides a
      critical self-organizing mechanism, by which ROP signaling is spatially limited
      to the growth site and temporally oscillates during continuous tip growth.
      Similar spatiotemporal control of Rho GTPase signaling may also play an important
      role in cell-polarity control in other systems, including tip growth in fungi and
      cell movement in animals.

PMID- 19108777
TI  - Characterization of PrEST-based antibodies towards human Cytokeratin-17.
AB  - Antibody-based proteomics efforts depend on validated antibodies to ensure
      correct annotation of analyzed proteins. We have previously argued that a low
      sequence identity to other proteins is a key feature for antigens used in
      antibody generation. Thus, a major challenge for whole-proteome studies is how to
      address families of highly sequence related proteins within the context of
      generating specific antibodies. In this study, two non-overlapping parts of human
      Cytokeratin-17, a protein belonging to the intermediate filament family of highly
      sequence-related proteins, were selected as a model system to study the
      specificity and cross reactivity of antibodies generated towards such a target.
      These recombinantly produced Protein Epitope Signature Tags (PrESTs) were
      immunized in five rabbits each and the batch-to-batch variations in the obtained
      immune responses were studied by mapping of linear epitopes using synthetic
      overlapping peptides. The obtained results showed a similar but not identical
      immune response in the respective antibody groups with a limited number of
      epitopes being identified. Immunohistochemical analysis of the affinity purified
      monospecific antibodies on tissue micro arrays resulted in a general recognition
      of human cytokeratins for all analyzed binders whereas antibodies identified as
      binding to the most unique parts of the PrESTs showed the most Cytokeratin-17
      like staining. The data presented here support the strategy to use sequence
      identity scores as the main criteria for antigen selection but also indicate the
      possibility to instead produce a single antibody recognizing a defined group of
      proteins when the intended targets overall sequence identity score is too high.
      This type of group-specific antibodies would be an important tool for antibody
      based projects aiming for a complete coverage of the human proteome.

PMID- 19108778
TI  - A quantitative measure of migratory connectivity.
AB  - The study of the extent of the connection between areas where populations of
      birds breed and areas where they winter has flourished in recent years mainly
      thanks to the development of new techniques, but also due to traditional ringing
      and recovery schemes, which allow tracking of individuals or populations linking
      wintering and breeding distributions. Currently, studies on migratory
      connectivity focus on retention of breeding population spatial structure on the
      non-breeding grounds and vice versa. Here we propose a method to quantify
      migratory connectivity based on Mantel correlation coefficients and to
      statistically test for deviations of the observed connectivity from a random mix
      of individuals. In addition, we propose a procedure, based on clustering
      algorithms, to identify whether observed connectivity depends on aggregation of
      individuals or on rigid transference of distribution patterns between areas. We
      applied this method to a large dataset of ringing recoveries of barn swallows
      (Hirundo rustica L) migrating from their Western Palearctic breeding areas to sub
      Saharan winter quarters. We show that migration of barn swallow populations
      connects specific breeding and wintering areas, and that the "sub-populations"
      quantitatively identified by our method are consistent with qualitative patterns
      of migratory connectivity identified by studies of individual geographical
      populations based on other methods. Finally, we tested the performance of the
      method by running simulations under different scenarios. Such simulations showed
      that the method is robust and able to correctly detect migratory connectivity
      even with smaller datasets and when a strong geographical pattern is not present
      in the population. Our method provides a quantitative measure of migratory
      connectivity and allows for the identification of populations showing high
      connectivity between the breeding and wintering areas. This method is suitable
      for a generalized application to diverse animal taxa as well as to large scale
      analyses of connectivity for conservation purposes.

PMID- 19108779
TI  - Evolution of microparasites in spatially and genetically structured host
      populations: the example of RHDV infecting rabbits.
AB  - Several studies have shown that classical results of microparasite evolution
      could not extend to the case where the host species shows an important spatial
      structure. Rabbit haemorrhagic disease virus (RHDV), responsible for rabbit
      haemorrhagic disease (RHD), which recently emerged in rabbits, has strains within
      a wide range of virulence, thus providing an interesting example of competition
      between strains infecting a host species with a metapopulation structure. In
      addition, rabbits may show a genetic diversity regarding RHDV susceptibility. In
      the present paper we use the example of the rabbit-RHDV interaction to study the
      competition between strains of a same microparasite in a host population that is
      both spatially and genetically structured. Using metapopulation models we show
      that the evolution of the microparasite is guided by a trade-off between its
      capacity to invade subpopulations potentially infected by other strains and its
      capacity to persist within the subpopulation. In such a context, host genetic
      diversity acts by reducing the number of hosts susceptible to each strain, often
      favouring more persistent-and generally less virulent-strains. We also show that
      even in a stochastic context where host genes regularly go locally extinct, the
      microparasite pressure helps maintain the genetic diversity in the long term
      while reinforcing gene loss risk in the short term. Finally, we study how
      different demographic and epidemiologic parameters affect the coevolution between
      the rabbit and RHDV.

PMID- 19108780
TI  - Fixation at a locus with multiple alleles: Structure and solution of the Wright
      Fisher model.
AB  - We consider the Wright Fisher model for a finite population of diploid sexual
      organisms where selection acts at a locus with multiple alleles. The mathematical
      description of a such a model requires vectors and matrices of a multidimensional
      nature, and hence has a considerable level of complexity. In the present work we
      avoid this complexity by introducing a simple mathematical transformation. This
      yields a description of the model in terms of ordinary vectors and ordinary
      matrices, thereby allowing standard linear algebra techniques to be directly
      employed. The new description yields a common mathematical representation of the
      Wright Fisher model that applies for arbitrary numbers of alleles. Within this
      framework, it is shown how the dynamics decomposes into component parts that are
      responsible for the different possible transitions of segregating and fixed
      populations, thereby allowing a clearer understanding of the population dynamics.
      This decomposition allows expressions to be directly derived for the mean time of
      fixation, the mean time of segregation (i.e., the sojourn time) and the
      probability of fixation. Numerical methods are discussed for the evaluation of
      these quantities.

PMID- 19108781
TI  - A kinematic model of stretch-induced stress fiber turnover and reorientation.
AB  - A kinetic model based on constrained mixture theory was developed to describe the
      reorganization of actin stress fibers in adherent cells in response to diverse
      patterns of mechanical stretch. The model was based on reports that stress fibers
      are pre-extended at a "homeostatic" level under normal, non-perturbed conditions,
      and that perturbations in stress fiber length destabilize stress fibers. In
      response to a step change in matrix stretch, the model predicts that stress
      fibers are initially stretched in registry with the matrix, but that these overly
      stretched fibers are gradually replaced by new fibers assembled with the
      homeostatic level of stretch in the new configuration of the matrix. In contrast,
      average fiber stretch is chronically perturbed from the homeostatic level when
      the cells are subjected to cyclic equibiaxial stretch. The model was able to
      describe experimentally measured time courses of stress fiber reorientation
      perpendicular to the direction of cyclic uniaxial stretch, as well as the lack of
      alignment in response to equibiaxial stretch. The model also accurately described
      the relationship between stretch magnitude and the extent of stress fiber
      alignment in endothelial cells subjected to cyclic uniaxial stretch. Further, in
      the case of cyclic simple elongation with transverse matrix contraction, stress
      fibers orient in the direction of least perturbation in stretch. In summary, the
      model predicts that the rate of stretch-induced stress fiber disassembly
      determines the rate of alignment, and that stress fibers tend to orient toward
      the direction of minimum matrix stretch where the rate of stress fiber turnover
      is a minimum.

PMID- 19108782
TI  - On the approaches applied in formulation of a kinetic model of photosystem II:
      Different approaches lead to different simulations of the chlorophyll alpha
      fluorescence transients.
AB  - Chlorophyll a fluorescence rise (O-J-I-P transient) was in literature simulated
      using models describing reactions occurring solely in photosystem II (PSII) and
      plastoquinone (PQ) pool as well as using complex models which described, in
      addition to the above, also subsequent electron transport occurring beyond the PQ
      pool. However, there is no consistency in general approach how to formulate a
      kinetic model and how to describe particular reactions occurring even in PSII
      only. In this work, simple kinetic PSII models are considered always with the
      same electron carriers and same type of reactions but some reactions are
      approached in different ways: oxygen evolving complex is considered bound to PSII
      or "virtually" separated from PSII; exchange of doubly reduced secondary quinone
      PSII electron acceptor, Q(B), with PQ molecule from the PQ pool is described by
      one second order reaction or by two subsequent reactions; and all possible
      reactions or only those which follow in logical order are considered. By
      combining all these approaches, eight PSII models are formulated which are used
      for simulations of the chlorophyll a fluorescence transients. It is shown that
      the different approaches can lead to qualitatively different results. The
      approaches are compared with other models found elsewhere in the literature and
      therefore this work can help the readers to better understand the other models
      and their results.

PMID- 19108783
TI  - The presence of generalist plant pathogens might not explain the long-term
      coexistence of plant species.
AB  - Pathogens have been shown to contribute to the possibility of coexistence of
      competing plant species by creating ecological distinction between the coexisting
      species. This coexistence promoting mechanism resembles intra-specific density
      dependence as found in Lotka-Volterra models. However, plant species adapt in
      their level of resistance against pathogen infection and this adaptation has been
      shown to be traded-off by a reduction in growth rate. A model is developed to
      show that taking into account the possible adaptation of plant species to
      increase their resistance against pathogen infection by generalist pathogens has
      consequences for the coexistence of the plant species. The results show that in
      systems where plants adapt to the pathogen infection, coexistence becomes
      impossible. The implication of this finding is that plant pathogens might
      contribute less to the coexistence of plant species than is commonly thought.

PMID- 19108784
TI  - Infliximab and methotrexate in the treatment of rheumatoid arthritis: a
      systematic review and meta-analysis of dosage regimens.
AB  - BACKGROUND: Because of its long-term effectiveness in clinical practice,
      methotrexate (MTX) is currently the preferred disease-modifying antirheumatic
      drug (DMARD) for patients with active rheumatoid arthritis (RRA). However, many
      patients do not experience remission and continue to have signs and symptoms of
      active disease while receiving a maximally tolerated dose. OBJECTIVES: The aims
      of this meta-analysis were to estimate the efficacy and tolerability of the
      various dosage schemes of infliximab versus MTX for the treatment of active RA,
      to eliminate size-related uncertainty of effects, and to identify subgroups of
      patients who benefit most from infliximab + MTX therapy. METHODS: Using the
      MEDLINE online database (inception through November 2006) and the Cochrane
      Database of Systematic Reviews (Issue 4, 2006), we identified English-language
      articles on randomized controlled clinical trials. Studies investigating
      infliximab + MTX regimens versus a control group receiving MTX alone to assess
      efficacy in active RA, using the American College of Rheumatology (ACR) criteria
      for 20% improvement (ACR20), 50% improvement (ACR50), and 70% improvement
      (ACR70), were considered eligible for the meta-analysis. Pooled odds ratios (ORs)
      and 95% CIs were calculated to compare the relative risks and benefits of adding
      infliximab to MTX. RESULTS: From a total of 78 initially identified studies, 42
      were considered potentially eligible for this review and 12 were considered
      eligible for the meta-analysis. Overall, 4899 patients were randomized to either
      infliximab + MTX (3919 patients) or MTX alone (980 patients). Mean patient age
      ranged from 44.6 to 56 years in the MTX-only arms and from 45.8 to 56 years in
      the infliximab + MTX arms. The proportion of female patients ranged from 66.6% to
      100% in the MTX arms and from 68% to 100% in the infliximab arms. Infliximab 3
      mg/kkg + MTX was more effective than MTX alone (OR = 3.52 [2.14-5.79] for
      reaching ACR20; 2.87 [2.228-3.61] for ACR50; and 2.42 [1.87-3.13] for ACR70).
      Infliximab 10 mg/kkg + MTX was also more effective than MTX alone (OR = 5.06
      [3.88-6.59] for reaching ACR20; 5.72 [4.05-8.08] for ACR50; and 7.32 [2.28-23.50]
      for ACR70). Infliximab 10-mm/kg regimens appeared to be more effective than
      infliximab 3-mg/kg regimens (P = NS, P = 0.001, and P = NS for reaching ACR20,
      ACR50, and ACR70, respectively), without being associated with an increased risk
      for adverse events. Infliximab 10 mg/kg appeared to be more effective in trials
      of longer duration (> or = 54 weeks) compared with those of shorter duration (P =
      0.03, P = 0.02, and P = 0.01 for reaching ACR20, ACR50, and ACR70, respectively)
      and in those that enrolled patients with severe disease activity (P = 0.05, P =
      0.05, and P = NS for reaching ACR20, ACR50, and ACR70, respectively). Steroid
      coadministration (P < 0.001, P < 0.001, and P = NS for reaching ACR20, ACR50, and
      ACR70, respectively), previous DMARD exposure (P < 0.001, P < 0.001, and P = 0.04
      for reaching ACR20, ACR50, and ACR70, respectively), and MTX naivete (P = NS, P <
      0.001, and P =0.013 for reaching ACR20, ACR50, and ACR70, respectively)
      correlated with higher infliximab efficacy. CONCLUSIONS: Based on this meta
      analysis, higher dose infliximab (10 mg/kg) in combination with MTX appeared to
      be more effective than the standard 3 mg/kg dose, particularly for patients with
      severe disease activity.The benefits of high-dose treatment appeared to accrue
      over time, and patients who received higher doses of infliximab did not
      experience a higher incidence of severe adverse events. The addition of oral low
      dose steroids significantly enhanced infliximab efficacy.

PMID- 19108785
TI  - Nilotinib: a second-generation tyrosine kinase inhibitor for the treatment of
      chronic myelogenous leukemia.
AB  - BACKGROUND: Nilotinib, a second-generation tyrosine kinase inhibitor (TKI)
      formerly known as AMN107, was approved by the US Food and Drug Administration
      (FDA) on October 29, 2007, for the treatment of adult patients with chronic-phase
      (CP) and accelerated-phase (AP) Philadelphia chromosome-positive (Ph+) chronic
      myelogenous leukemia (CML) resistant to or intolerant of prior treatment that
      included imatinib. OBJECTIVE: The purpose of this review was to evaluate the
      pharmacology, pharmacokinetic properties, and pharmacodynamic properties of
      nilotinib; results of clinical trials in patients with CML, Ph+ acute
      lymphoblastic leukemia (ALL), and gastrointestinal stromal tumors (GISTs); and
      potential drug interactions. METHODS: Literature was identified and reviewed
      using searches of MEDLINE (1966-April 1, 2008), the American Society of
      Hematology and American Society of Clinical Oncology abstracts databases (2002
      2008 annual meetings/symposia), the European Hematology Association abstracts
      database (2006-2007 annual meetings), and the American Association for Cancer
      Research symposia (2000-2007). Search terms included, but were not limited to,
      nilotinib, AMN107, chronic myelogenous leukemia, acute lymphoblastic leukemia,
      bcr-abl, imatinib resistance, adverse events, pharmacology, and clinical trials.
      RESULTS: Nilotinib is an orally bioavailable derivative of imatinib with improved
      specificity toward the breakpoint cluster region-Abelson murine leukemia (bcr
      abl) viral protooncogene. In preclinical studies, nilotinib was found to have
      activity against 32 of 33 imatinib-resistant bcr-abl mutations, but not against
      the T3151 mutation. On pharmacokinetic analysis, T(max) was 3 hours. The
      calculated t((1/2)) following multiple daily dosing was approximately 17 hours.
      The main metabolic pathways identified were oxidation and hydroxylation. The
      parent compound is the circulating component found in serum; the metabolites were
      not found to contribute to pharmacologic activity. Nilotinib is a competitive
      inhibitor of cytochrome P450 (CYP) 3A4, CYP2C8, CYP2C9, and CYP2D6. In 2 Phase
      II, open-label, single-arm clinical studies, nilotinib was found to be beneficial
      in patients with CML that was imatinib resistant or intolerant. Overall, 58% of
      patients with CML-CP achieved a major cytogenetic response; 42%, a complete
      cytogenetic response; and 77%, a complete hematologic response (CHR). At 18
      months, the estimated overall survival rate was 91%. Of patients whose disease
      had progressed to AP, nilotinib was associated with major cytogenetic response in
      32%; complete cytogenetic response in 19%; and CHR in 30%. At 12 months, an
      estimated 56% of patients lacked progression of disease, and the estimated
      overall survival rate was 82%. Concurrent use of CYP3A4 inhibitors should be
      avoided. The most common toxicities attributable to nilotinib include rash,
      pruritus, nausea, fatigue, headache, constipation, diarrhea, and vomiting. Grade
      3/4 toxicities (> or = 10%) have included thrombocytopenia, neutropenia, elevated
      lipase, hyperglycemia, and hypophosphatemia. Nilotinib has been associated with a
      prolonged QT interval, and sudden death has been reported. The FDA-approved
      regimen of nilotinib is 400 mg PO BID on an empty stomach. CONCLUSIONS: Nilotinib
      is an oral second-generation bcr-abl TKI indicated for the treatment of imatinib
      resistant or -intolerant Ph+ CML-CP and -AP in adults. Positive clinical activity
      and tolerability have been reported in clinical trials. Clinical data on off
      label indications and in patients with Ph+ ALL and GIST continue to emerge.

PMID- 19108786
TI  - A 52-week, multinational, open-label, parallel-group, noninferiority, treat-to
      target trial comparing insulin detemir with insulin glargine in a basal-bolus
      regimen with mealtime insulin aspart in patients with type 2 diabetes.
AB  - OBJECTIVE: This trial compared the efficacy and safety profiles of the insulin
      analogues detemir and glargine as the basal insulin component of a basal-bolus
      regimen in patients with type 2 diabetes mellitus (T2DM) who were being treated
      with oral antidiabetic drugs (OADs) or insulin with or without OADs. METHODS:
      This was a multinational, 52-week, openlabel, parallel-group, noninferiority,
      treat-to-target trial. Patients with a diagnosis of T2DM for > or = 12 months who
      had been receiving an OAD or insulin, with or without OADs, for > 4 months were
      randomized in a 2:1 ratio to receive detemir or glargine. According to the
      approved labeling, detemir could be administered once or twice daily, and
      glargine was administered once daily. Insulin aspart was given at mealtimes.
      Insulin secretagogues and a-glucosidase inhibitors were discontinued at study
      entry, and existing OADs were continued. Doses of detemir and glargine were
      titrated to achieve a prebreakfast (and predinner for detemir administered twice
      daily) plasma glucose target of < or = 6.0 mmol/L. Patients monitored their
      plasma glucose levels before breakfast and dinner on the 3 days before each of 13
      scheduled visits, recorded their insulin doses on 1 of these 3 days, and recorded
      their 10-point self-monitored plasma glucose (SMPG) at baseline and after 24 and
      52 weeks. The primary efficacy end point was glycosylated hemoglobin (HbA(1c)) at
      52 weeks; secondary efficacy end points included changes in fasting plasma
      glucose (FPG), postprandial plasma glucose, insulin doses, and weight change at
      52 weeks. Safety end points included the frequency of hypoglycemia and adverse
      events (AEs). RESULTS: The intention-to-treat population included 319 patients
      (58.0% male, 42.0% female; 78.4% white; mean age, 58 years; mean weight, 92.8 kg;
      mean duration of diabetes, 13.6 years). At study entry, 46.1% of patients were
      receiving insulin and > or = 1 OAD, 35.4 were receiving insulin only, and 18.5%
      were receiving > or = 1 OAD only. At 52 weeks, there was no significant
      difference between detemir and glargine in terms of mean HbA(1c) (7.19% and
      7.03%, respectively; mean difference, 0.17% [95% CI, -0.07 to 0.40]) or the mean
      decrease in HbAlc from baseline (-1.52% and -1.68%). The reduction in HbA(1c) was
      not significantly affected by whether detemir was administered once or twice
      daily. There were no significant differences between groups in terms of mean FPG
      (7.05 and 6.68 mmol/L) or the mean change in FPG from baseline (-2.56 and -2.92
      mmol/L; mean difference, 0.36; 95% CI, -0.26 to 0.99). The overall shape of the
      10-point SMPG profiles was not significantly different between groups. Mean
      weight gain at 52 weeks was significantly lower with detemir than with glargine
      (2.8 vs 3.8 kg; mean difference, -1.04; 95% CI, -2.08 to -0.01; P < 0.05). Doses
      of basal and prandial insulins at the end of the study were not significantly
      different between groups. Major hypoglycemic episodes were reported by 4.7% and
      5.7% of patients in the respective treatment groups. There was no significant
      difference in the risk of hypoglycemia between groups. The proportion of patients
      with AEs and the number of AEs per patient were comparable between groups
      (185/214 patients [86.4%] reporting 743 AEs and 88/105 patients [83.8%] reporting
      377 AEs). CONCLUSIONS: when used as indicated as part of a basal-bolus regimen in
      patients with T2DM who had previously received other insulin and/or OAD regimens,
      detemir was noninferior to glargine in its effects on overall glycemic control.
      Both basal insulins were associated with clinically relevant reductions in
      hyperglycemia. Both were well tolerated, with no significant difference in the
      frequency of hypoglycemia or AEs.

PMID- 19108787
TI  - Milnacipran for the treatment of fibromyalgia in adults: a 15-week, multicenter,
      randomized, double-blind, placebo-controlled, multiple-dose clinical trial.
AB  - BACKGROUND: Preclinical and clinical studies have suggested that milnacipran, a
      dual norepinephrine-serotonin reuptake inhibitor, may be efficacious in the
      treatment of fibromyalgia (FM). OBJECTIVE: This study was conducted to evaluate
      the efficacy and tolerability of milnacipran in treating the multiple domains of
      FM. METHODS: This was a multicenter, double-blind, placebo-controlled trial.
      Adult patients (age 18-70 years) who met 1990 American College of Rheumatology
      criteria for FM were randomized to receive milnacipran 100 mg/d, milnacipran 200
      mg/d, or placebo for 15 weeks. Because this was a pivotal registration trial, the
      primary end points were chosen to investigate efficacy for 2 potential
      indications: the treatment of FM and the treatment of FM pain. Thus, the 2
      primary efficacy end points were rates of FM composite responders and FM pain
      composite responders. FM composite responders were defined as patients
      concurrently experiencing clinically meaningful improvements in the following 3
      domain criteria: pain (> or = 30% improvement, as recorded in an electronic
      diary); patients' global status (a rating of very much improved or much improved
      on the Patient Global Impression of Change [PGIC] scale); and physical function
      (a > or = 6-point improvement on the 36-item Short-Form Health Survey [SF-36]
      Physical Component Summary score). FM pain composite responders were defined as
      those who met the pain and PGIC criteria. Adverse events reported by patients or
      observed by investigators were recorded throughout the trial. RESULTS: Of 2270
      patients screened, 1196 were randomized to receive milnacipran 100 mg/d (n =
      399), milnacipran 200 mg/d (n = 396), or placebo (n = 401). The majority of
      patients were female (96.2%) and white (93.5%). The population had a mean age of
      50.2 years, a mean baseline weight of 180.8 pounds, and a mean baseline body mass
      index of 30.6 kg/m(2). Compared with placebo, significantly greater proportions
      of milnacipran-treated patients were FM composite responders (100 mg/d: P = 0.01;
      200 mg/d: P = 0.02) and FM pain composite responders (100 mg/d: P = 0.03; 200
      mg/d: P = 0.004). Milnacipran was associated with significant improvements in
      pain after 1 week of treatment (100 mg/d: P = 0.004; 200 mg/d: P = 0.04), as well
      as significant improvements in multiple secondary efficacy end points, including
      global status (PGIC: P<0.001 for both doses), physical function (SF-36 physical
      functioning domain-100 mg/d: P < 0.001; 200 mg/d: P = 0.02), and fatigue
      (Multidimensional Fatigue Inventory- 100 mg/d: P = 0.04). The most commonly
      reported adverse events with milnacipran were nausea (100 mg/d, 34.3%; 200 mg/d,
      37.6%), headache (18.0% and 17.7%, respectively), and constipation (14.3% and
      17.9%). Adverse events resulted in premature study discontinuation in 19.5% and
      23.7% of those who received milnacipran 100 and 200 mg/d, respectively, compared
      with 9.5% of placebo recipients. CONCLUSION: In these adult patients with FM,
      both doses of milnacipran (100 and 200 mg/d) were associated with significant
      improvements in pain and other symptoms. Clinical Trials Identification Number:
      NCT00098124.

PMID- 19108788
TI  - Conjunctival tissue pharmacokinetic properties of topical azithromycin 1% and
      moxifloxacin 0.5% ophthalmic solutions: a single-dose, randomized, open-label,
      active-controlled trial in healthy adult volunteers.
AB  - BACKGROUND: Effective ocular tissue concentrations and prolonged residence times
      of antibacterial agents are important in treating both acute and chronic
      diseases. Conjunctival biopsy allows the determination of specific tissue
      concentration data for topical ophthalmic agents. Drug concentration analysis at
      various time points following instillation allows interpretation of the residence
      time and a rationale for dosing frequency. OBJECTIVE: This study compared the
      pharmacokinetic parameters of 2 currently available topical ocular antibiotics
      azithromycin ophthalmic solution 1% and moxifloxacin ophthalmic solution 0.5%-in
      the conjunctiva of healthy volunteers after a single topical administration.
      METHODS: This single-dose, randomized, open-label, active-controlled clinical
      trial was conducted at ORA Clinical Research and Development, North Andover,
      Massachusetts. Subjects were randomly assigned to receive a single dose of
      azithromycin or moxifloxacin and to undergo biopsy sampling at 30 minutes or 2,
      12, or 24 hours after administration. Concentrations of azithromycin and
      moxifloxacin were determined using liquid chromatography tandem mass
      spectrometry. Adverse events (AEs) were assessed at all visits using visual
      acuity measurements, slit-lamp biomicroscopy, and direct questioning. RESULTS:
      Forty-eight subjects (mean age, 40.0 years; 48% female; 96% white, 2% black, and
      2% Asian) underwent conjunctival biopsy. Mean (SD) concentrations of azithromycin
      in conjunctival tissue (lower limit of quantitation [LLOQ], 1 microg/g for 1-mg
      biopsy specimen) were 131 (89), 59 (19), 48 (24), and 32 (20) microg/g at 30
      minutes and 2, 12, and 24 hours, respectively (median values, 117, 69, 46, and 30
      microg/g). Mean concentrations concentrations of moxifloxacin in conjunctival
      tissue (LLOQ, 0.05 microg/g for 1-mg biopsy sample) were 1.92 (2.03), 3.77
      (8.98), 0.02 (0.04), and 0.01 (0.02) microg/g at 30 minutes and 2, 12, and 24
      hours, respectively (median values, 1.12, 0.12, <0.05, and <0.05 microg/g).
      Thirteen subjects (6 in the azithromycin group and 7 in the moxifloxacin group)
      experienced 20 AEs, 11 of which were considered possibly related to study
      treatment, and 15 of which were ocular (most commonly conjunctival hemorrhage).
      CONCLUSIONS: In this single-dose study of 2 currently available topical ocular
      antibiotics in healthy volunteers, therapeutic concentrations were achieved with
      both agents. Both treatments were well tolerated in the population studied.
      Clinical Trials Identification Number: NCT00564447.

PMID- 19108789
TI  - Bioequivalence of two levothyroxine tablet formulations without and with
      mathematical adjustment for basal thyroxine levels in healthy Argentinian
      volunteers: a single-dose, randomized, open-label, crossover study.
AB  - BACKGROUND: Levothyroxine has a narrow therapeutic index; therefore, precise and
      accurate assessment of the bioequivalence of different levothyroxine products is
      critical. Bioavailability estimates of levothyroxine formulations might be
      affected by baseline concentrations of the hormone. OBJECTIVES: The aim of this
      study was to assess the bioequivalence of 100 microg of a test (T4 Montpellier
      100, Quimica Montpellier S.A., Buenos Aires, Argentina) and reference (Synthroid,
      Abbott Laboratories, Abbott Park, Illinois) formulation of levothyroxine. We also
      compared 2 methods of levothyroxine measurements: without and with baseline
      correction for endogenous levothyroxine. METHODS: This randomized, open-label, 2
      sequence, crossover study with a 65-day washout period was carried out in
      healthy, white, euthyroid volunteers following a single dose of sodium
      levothyroxine 600 microg. Blood samples were collected at 30 and 15 minutes prior
      to administration, and 0 (baseline), 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12, 24,
      and 48 hours to determine thyroxine; serum thyrotropin (TSH) concentrations were
      determined 30 minutes before administration and 48 hours after administration.
      Serum concentrations of thyroxine were determined through radioimmunoassay and
      serum TSH concentrations were determined by a validated 2-site immunoradiometric
      assay. The formulations are considered to be equivalent if the 90% CI ratios for
      C(max) and AUC(0-last) are within 80% to 125%, per the US Food and Drug
      Administration (FDA). Adverse event monitoring was performed throughout the study
      by assessing clinical parameters (eg, blood pressure, electrocardiogram) and
      patient reports. RESULTS: A total of 24 volunteers (16 male, 8 female; mean [SD]
      age, 30.2 [4.6] years [range, 21-40 years]; mean [SD] weight, 71.71 [7.52] kg
      [range, 58-83 kg]) were included in the study. Without adjustment for baseline
      levels of endogenous levothyroxine, geometric mean C(max) for the test and
      reference formulations were 8.92 and 9.39 microg/dL, respectively; AUC(0-last)
      values were 368.40 and 383.37 microg/mL . h(-1). The 90% CI of the geometric mean
      for the percent ratios (test: reference) of C(max) and AUC(0-last) were 95.1%
      (90% CI, 91.9-98.3) and 96.1% (90% CI, 94.0-98.2), respectively. With adjustment
      for baseline levels of endogenous levothyroxine, the geometric mean C(max) for
      the test and reference formulations were 3.16 and 3.39 microg/dL, respectively;
      AUC(0-last) values were 88.33 and 95.60 microg/mL . h(-1). Despite performing the
      adjustment, the 90% CI of the geometric mean for Cmax and AUC(0-last)
      test:reference ratios were 93.1% (90% CI, 84.9-102.2) and 92.4% (90% CI, 85.2
      100.2), respectively. No significant between-group differences were found with
      regard to pharmacokinetic parameters. No adverse events were observed or
      reported. CONCLUSION: The results of this study suggest that the test formulation
      was bioequivalent to the reference formulation of levothyroxine in these healthy
      volunteers, according to the US FDA definition of bioequivalence. This was
      supported by the analysis of concentration-time profiles without and with
      correction for basal endogenous levothyroxine.

PMID- 19108790
TI  - Comparison of propofol, droperidol, and metoclopramide for prophylaxis of
      postoperative nausea and vomiting after breast cancer surgery: a prospective,
      randomized, double-blind, placebo-controlled study in Japanese patients.
AB  - BACKGROUND: Breast cancer surgery performed with the patient under general
      anesthesia has been associated with a relatively high incidence of postoperative
      nausea and vomiting (PONV). Between 60% and 80% of patients who undergo
      mastectomy (with axillary dissection) experience PONV. We previously reported
      that propofol at a subhypnotic dose of 0.5 mg/kg was more effective than placebo
      in preventing PONV in women who undergo mastectomy. OBJECTIVE: The purpose of
      this study was to compare the efficacy of a subhypnotic dose of propofol with the
      conventional antiemetics droperidol and metoclopramide for the prophylaxis of
      PONV after breast cancer surgery in Japanese patients. METHODS: In this
      prospective, randomized, double-blind, placebo-controlled study, Japanese women
      were randomized to 1 of 4 groups to receive IV administration of propofol 0.5
      mg/kg, droperidol 20 microg/kg, metoclopramide 0.2 mg/kg, or placebo (isotonic
      saline) immediately after skin suture. A standard general anesthetic technique,
      including sevoflurane and air in oxygen, was used. All episodes of PONV during
      the first 24 hours after anesthesia administration were recorded by an
      investigator who was blinded to treatment assignment. The investigator questioned
      the patients as to whether they experienced extrapyramidal symptoms. To maintain
      the integrity of the study results, none of the patients received preanesthetic
      medication. RESULTS: A total of 100 women (mean [SD] age, 52 [7] years; height,
      154 [6] cm; weight, 54 [7] kg) were included in the study. Each study group
      comprised 25 patients. There were no significant differences between treatment
      groups with regard to patient demographics, surgery type, or awakening time. The
      prevalences of PONV 0 to 24 hours after anesthesia were 28% with propofol (P =
      0.005), 32% with droperidol (P = 0.011), and 60% with metoclopramide (P = NS),
      compared with placebo (68%). No significant difference in the prevalence of PONV
      was found between patients receiving propofol and those receiving droperidol, and
      propofol and droperidol were associated with significantly lower prevalences of
      PONV compared with metoclopramide (P = 0.022 and P = 0.043, respectively).
      Extrapyramidal symptoms were not reported in any of the groups. CONCLUSIONS: The
      prevalences of PONV were not significantly different between propofol 0.5 mg/kg
      and droperidol 20 microg/kg 0 to 24 hours after anesthesia in this small, select
      group of Japanese women who underwent breast cancer surgery. The prevalences of
      PONV were significantly lower with propofol and droperidol compared with
      metoclopramide 0.2 mg/kg and placebo.

PMID- 19108791
TI  - A 16-week, randomized, double-blind, placebo-controlled, crossover trial to
      quantify the combined effect of an angiotensin-converting enzyme inhibitor and a
      beta-blocker on blood pressure reduction.
AB  - BACKGROUND: Although beta-blockers and angiotensin-converting enzyme (ACE)
      inhibitors are often used together, there is a lack of quantitative evidence for
      the efficacy of this combination in reducing blood pressure (BP). OBJECTIVE: The
      aim of this randomized, double-blind, placebo-controlled, crossover study was to
      quantify the combined effect of a beta-blocker (atenolol) and an ACE inhibitor
      (lisinopril) in lowering BP. METHODS: Participants who were > or = 40 years of
      age and enrolled in the hypertension or anticoagulation clinics at St.
      Bartholomew's Hospital, London, United Kingdom, were randomized to 3 consecutive
      4-week treatments consisting of atenolol 25 mg plus placebo, lisinopril 5 mg plus
      placebo, and atenolol 25 mg plus lisinopril 5 mg, plus a period of 2 placebos. At
      the end of each period, seated BP was measured in the right arm using electronic
      monitors. RESULTS: The mean placebo-adjusted peak BP reductions among the 47
      participants (mean age, 62 [range 42-82] years; 75% male; 70% white/30% Asian;
      mean baseline BP, 145/82 mm Hg) who completed all 4 periods were significantly
      greater with the combination of both drugs than with either drug alone (P <
      0.001). The systolic reductions were 22.9 mm Hg with combination treatment, 16.1
      mm Hg with atenolol treatment, and 12.5 mm Hg with lisinopril treatment, and the
      diastolic reductions were 13.9, 9.8, and 6.8 mm Hg, respectively. The BP-lowering
      effect of the 2 drugs together was similar to that expected from the sum of each
      alone, allowing for the reduced effect of 1 drug given the lower pretreatment BP
      due to the other. The incremental systolic BP reduction from the 2 drugs together
      compared with 1 alone was 79% (95% CI, 54%-126%) of the expected additive effect,
      88% (95% CI, 58%-130%) for diastolic BP, and 84% (95% CI, 65%-118%) for the mean
      of systolic and diastolic BP. CONCLUSIONS: The combination of the beta-blocker
      atenolol 25 mg plus the ACE inhibitor lisinopril 5 mg was associated with a
      significantly greater decrease in BP compared with either alone. The BP reduction
      with the combination treatment was similar to and statistically consistent with
      the 2 drugs having additive effects. Clinical Trials Identification Number:
      ISRCTN97280940.

PMID- 19108792
TI  - Update on antimicrobial susceptibility rates among gram-negative and gram
      positive organisms in the United States: results from the Tigecycline Evaluation
      and Surveillance Trial (TEST) 2005 to 2007.
AB  - BACKGROUND: The Tigecycline Evaluation and Surveillance Trial (TTEST) is a global
      surveillance study initiated in 2004.Its goal is to assess the in vitro activity
      of the glycylcycline, tigecycline, and comparator antimicrobials. OBJECTIVE: The
      aim of this study was to measure the in vitro activity of a panel of
      antimicrobial agents against gram-negative and gram-positive organisms collected
      in the United States in 2005, 2006, and 2007. METHODS: Isolates were collected
      from 172 centers across the United States.In vitro activity was assessed using
      Clinical and Laboratory Standards Institute (CLSI) guidelines and CLSI or US Food
      and Drug Administration interpretive criteria. RESULTS: Overall, data on 20,897
      gram-negative and 8949 gram-positive isolates were collected. For the majority of
      organisms, percentage susceptibilities were unchanged over the 3 years of
      collection. One exception was Acinetobacter baumannii; rates of susceptibility to
      the majority of agents in the panel decreased by approximately 10% over the 3
      years. Rates of resistant phenotypes were relatively unchanged with mean
      percentages over the 3 years of: 8.9% (337/3787) for extended beta-spectrum beta
      lactamase (ESBL)-producing Klebsiella pneumoniae; 2.1% (17/801) for ESBL
      producing Klebsiella oxytoca; 2.3% (111/4861) for ESBL-pproducing Escherichia
      coli; 56.2% (2564/4560) for methicillin-resistant Staphylococcus aureus; 5.1%
      (97/1903) for vancomycin-resistant Enterococcus faecalis; and 67.2% (487/725) for
      vancomycin-resistant Enterococcus faecium. The minimum inhibitory concentration
      required to inhibit the growth of 90% of organisms (MIC(90)) for tigecycline was
      stable over the 3 years and was < or = 22 mg/L against non-ESBL-producing K
      pneumoniae, K oxytoca, E coli, Enterobacter aerogenes, Enterobacter cloacae,
      Serratia marcescens, and A baumannii. Against methicillin susceptible and 
      resistant S aureus, E faecalis, E faecium, and Streptococcus agalactiae
      tigecycline MIC(90)s were < or = 0.25 mg/L. CONCLUSIONS: This report of 3 years
      of data from the TEST study suggests stable susceptibility rates among gram
      negative and gram-positive organisms, with the exception of decreased
      susceptibility rates for A baumannii. Tigecycline continued to have good activity
      against Enterobacteriaceae, A baumannii, S aureus, E faecalis, E faecium, and S
      agalactiae.

PMID- 19108793
TI  - Single- and multiple-dose pharmacokinetic evaluation of oxycodone and naloxone in
      an opioid agonist/antagonist prolonged-release combination in healthy adult
      volunteers.
AB  - BACKGROUND: There is an increasing body of evidence supporting the need for
      prophylactic management of the adverse events (AEs) associated with long-term
      opioid use in patients with chronic pain. Symptoms of bowel dysfunction, such as
      constipation, may have a significant impact on a patient's quality of life and
      willingness to continue opioid therapy, and therefore should be managed
      proactively to ensure that the patient can continue effective pain management.
      The fixed-dose combination (FDC) prolonged-release (PR) oxycodone/naloxone (OXN)
      may be an effective therapeutic approach to delivering analgesia, with a reduced
      risk for opioid-induced constipation. OBJECTIVE: The aim of this paper was to
      report the pharmacokinetic results from a single-dose study and a multiple-dose
      bioequivalence study of OXN versus separate formulations of oxycodone PR and
      naloxone PR administered concurrently in healthy subjects. METHODS: Both studies
      were open-label, randomized crossover studies in healthy adult male and female
      subjects. In the single-dose study, subjects were randomly assigned to 1 of 4
      treatment groups: OXN FDC (44 x 10/55-mg, 2 x 20/110-mg, or 1 x 40/20-mg dose
      strength [each given at a total combined dose of 40/220 mg]) or oxycodone PR 40
      mg + naloxone PR 20 mg given in separate formulations. In the multiple-dose
      study, 34 subjects were randomly assigned to 1 of 3 treatment groups: OXN FDC
      40/20 mg, oxycodone PR 40 mg, or naloxone PR 20 mg. Treatments were considered
      bioequivalent if the 90% CIs for relative bioavailability calculations fell
      within a predetermined range of 80% to 125%. AEs were assessed by the
      investigator at each study visit. RESULTS: The single-dose study included 28
      subjects (22 men, 6 women; mean [SD] age, 32.3 [5.44] years; weight, 75.5 [9.3]
      kg; and body mass index [BMI], 24.2 [2.5] kg/mm(2)). The mean plasma oxycodone
      concentration-time curves for OXN and oxycodone PR + naloxone PR were similar.
      With oxycodone, the mean (SD) AUC(t) values with OXN 10/5, 20/10, and 40/20 mg
      and oxycodone PR + naloxone PR were 473.49 (72.16), 491.22 (82.18), 488.89
      (91.04), and 502.28 (84.13) ng . h/mL, respectively; mean C(max) values were
      34.91 (4.36), 35.73 (4.93), 34.46 (5.03), and 40.45 (4.71) ng/mL. For naloxone-3
      glucuronide (the primary analyte of naloxone), the mean (SD) AUC(t) values with
      OXN 10/5, 20/10, and 40/20 mg and oxycodone PR + naloxone PR were 539.93
      (142.24), 522.45 (128.57), 520.10 (133.18), and 523.37 (119.75) ng . h/mL,
      respectively; mean C(max) values were 62.01 (15.96), 63.62 (19.51), 61.95
      (18.37), and 63.55 (16.75) ng/mL. There were no statistically significant
      differences between the treatments, and each of the treatment comparisons
      resulted in 90% CIs within the range for bioequivalence. The multiple-dose steady
      state bioequivalence study included 34 subjects (28 men, 6 women; mean [SD] age,
      36 [9.4] years; weight,78.9 [11.7] kg; and BMI, 24.6 [1.9] kg/m(2)). No
      significant differences were observed between the treatments, with the exception
      of naloxone-3-glucuronide C(min,ss) values. Mean C(min,ss) values of 22.6 and
      24.0 ng/mL were obtained for the OXN combination and naloxone PR tablet,
      respectively. In the multiple-dose study, the most frequently reported AEs with
      OXN,oxycodone PR, and naloxone PR were headache (7%, 26%, and 17%, respectively),
      anorexia (10%, 16%, and 13%), and nausea (10%, 13%, and 7%). CONCLUSIONS: The
      results from the single-dose study were consistent with the regulatory definition
      of bioequivalence of the FDCs and single components across the range of doses
      administered. The pharmacokinetic properties of the OXN FDC were similar to those
      of oxycodone PR + naloxone PR given as separate formulations, based on the
      regulatory definition. These findings were consistent with the results of the
      multiple-dose steady-state bioequivalence study. In this population of healthy
      volunteers, the pharmacokinetic properties of oxycodone apparently were not
      significantly influenced by administering oxycodone in a combination product, and
      the availability of naloxone-3-glucuronide from OXN was similar to that from the
      naloxone PR tablet. These findings suggest that the coadministration of oxycodone
      PR and naloxone PR in an FDC would not significantly affect the bioavailability
      of either of its constituents in these subjects.

PMID- 19108794
TI  - Adverse drug reactions to treatments for ocular toxoplasmosis: a retrospective
      chart review.
AB  - OBJECTIVE: This study evaluated the incidence and types of adverse drug reactions
      (ADRs) associated with medications used to treat active toxoplasmic
      chorioretinitis. METHODS: This was a retrospective review of the clinical records
      of a consecutive series of patients with active toxoplasmic chorioretinitis,
      examined between March 1991 and August 1998. For inclusion in the review,
      patients had to have been diagnosed with active toxoplasmic chorioretinitis, been
      treated with a single drug or drug combination indicated for this condition, and
      been followed for at least 8 weeks. Patients who were lost to follow-up or who
      had incomplete chart data were excluded. Demographic data, pertinent aspects of
      the medical history, drug treatments, and ADRs associated with antitoxoplasmic
      treatment were recorded. RESULTS: Fifty-five patients met the criteria for
      inclusion in the review. In descending order of frequency, they received
      antitoxoplasmic treatment with clindamycin (n = 50), sulfadiazine (n = 40),
      pyrimethamine (n = 33), trimethoprim-sulfamethoxazole (n = 16), and atovaquone (n
      = 10), alone or in combination. Twenty-two patients (40.0%) had a total of 27
      ADRs. The most frequently occurring ADRs were rash (19 [34.5%]), mostly
      associated with sulfadiazine (9/40 [22.5%]) and clindamycin (6/50 [12.0%]), and
      gastrointestinal ADRs such as diarrhea (6 [10.9%]), stomach upset (6 [10.9%]),
      and bleeding (1 [1.8%]), mostly associated with clindamycin (5/50 [10.0%], 3/50
      [6.0%], and 1/50 [2.0%], respectively). The incidence of ADRs associated with
      individual antitoxoplasmic drugs was 30.0% (3/10) for atovaquone, 26.0% (13/50)
      for clindamycin, 22.5% (9/40) for sulfadiazine, 12.5% (2/16) for trimethoprim
      sulfamethoxazole, and 12.1% (4/33) for pyrimethamine. There were 2 serious ADRs:
      gastrointestinal bleeding in a patient treated with clindamycin and leukopenia in
      a patient treated with pyrimethamine. Twenty-five ADRs were reversed on drug
      discontinuation; the remaining 2 were mild and did not require drug
      discontinuation. CONCLUSIONS: The overall incidence of treatment-associated ADRs
      was high (40.0%) in these patients with ocular toxoplasmosis. The most frequently
      occurring ADRs were rash and gastrointestinal complaints.

PMID- 19108795
TI  - Stability of doripenem in vitro in representative infusion solutions and infusion
      bags.
AB  - BACKGROUND: Doripenem, a new parenteral carbapenem with broad-spectrum
      antibacterial activity, is indicated for the treatment of complicated intra
      abdominal infections and complicated urinary tract infections, including
      pyelonephritis. According to the US prescribing information, the carbapenems
      imipenem and meropenem are stable in sodium chloride for 4 hours. OBJECTIVE: The
      aim of this study was to assess the stability of doripenem following constitution
      (50 mg/mL) and in injection solutions in vitro (0.9% sodium chloride and 5%
      dextrose) at a concentration of 5 mg/mL in room and refrigerated conditions.
      METHODS: The stability of doripenem was assessed (1) under room-temperature
      conditions (25 degrees C +/- 2 degrees C, 60% +/- 5% relative humidity, under
      fluorescent light) immediately after constitution in vials with sterile water;
      (2) under room conditions and refrigerated conditions (5 degrees C +/- 3 degrees
      C, 60% relative humidity, protected from light) immediately after constitution
      with sodium chloride or dextrose in 3 different infusion bags (polyvinyl chloride
      [PVC], PVC with vial adapter, and polyethylene); and (3) under room and
      refrigerated conditions using 500-mg doripenem vials that had been stored for 12
      months in room temperature and protected from light before constitution with
      water and dilution in sodium chloride or dextrose injection. Doripenem 5 mg/mL
      and related substances (degradation products and impurities related to doripenem)
      were measured using a validated high-performance liquid chromatography method.
      Doripenem was considered stable if its concentration remained within 90% to 110%
      of the initial concentration and the total concentration of degradation products
      and impurities related to doripenem was < or = 5%. Appearance of the solutions
      was assessed using clarity and comparison to color standards; pH, using standard
      methodologies; and particulate matter, using light-obscuration and microscopy.
      RESULTS: Three lots of doripenem were assessed. Doripenem potency in constituted
      suspension (50 mg/mL) remained unchanged (means, 99.2% and 99.3%, respectively,
      of initial doripenem amount) for up to 60 minutes in room or refrigerated
      conditions prior to transfer to infusion bags. The doripenem 5-mg/mL infusion
      solution retained its potency for 12 and 72 hours under room and refrigerated
      conditions, respectively, in 0.9% sodium chloride injection, and for 4 and 48
      hours under room and refrigerated conditions, respectively, in 5% dextrose
      injection (mean percentages of initial doripenem concentration, 95.5% and 96.6%
      under room and refrigerated conditions, respectively). Comparable results were
      obtained with vials of doripenem that had been stored for 12 months at room
      temperature and protected from light and then constituted (50 mg/mL). Doripenem 5
      mg/mL in 0.9% sodium chloride injection or 5% dextrose injection retained its
      potency in room conditions at the end of a 4-hour drip period when used with
      conventional infusion sets (mean, 96.6%) or Di(2-ethylhexyl)phthalate-free
      infusion sets (mean, 99.3%). CONCLUSIONS: Doripenem 5 mg/mL was stable for up to
      12 hours in vitro in 0.9% sodium chloride at room temperature. Therefore,
      doripenem can be constituted, mixed with infusion fluids in the pharmacy, stored,
      delivered, and infused into a patient within a time frame suitable for 4-hour
      extended infusions.

PMID- 19108796
TI  - Susceptibility of Escherichia coli strains isolated from outpatient children with
      community-acquired urinary tract infection in southern Switzerland.
AB  - BACKGROUND: Based on antimicrobial resistance patterns found in Swiss university
      hospitals, treatment with a third-generation cephalosporin is currently advised
      for Swiss children with urinary tract infection. OBJECTIVE: The aim of this study
      was to prospectively assess the susceptibility of Escherichia coli strains
      isolated from children with symptomatic community-acquired urinary tract
      infection. METHODS: The antimicrobial susceptibility of E coli strains causing
      symptomatic community-acquired urinary tract infections was assessed in
      outpatient children attending the emergency management unit at the Department of
      Pediatrics, Mendrisio and Bellinzona Hospitals, Switzerland. Strains from
      children receiving antimicrobial prophylaxis or prescribed antimicrobials in the
      previous 4 weeks were excluded. Clinical and Laboratory Standards Institute
      methods were used for culture and identification of pathogens. E coli
      susceptibility testing was performed using the disk diffusion technique. RESULTS:
      Strains from 100 consecutive outpatient children (73 girls, 27 boys; aged 5 weeks
      17 years [median, 33 months]; 100% white) were assessed. High rates of ampicillin
      and cotrimoxazole resistance (39 and 21 strains, respectively) and low rates of
      nitrofurantoin resistance (4 strains) were identified. No resistance was
      identified for coamoxiclav or third-generation cephalosporins. CONCLUSIONS: In
      these Swiss outpatient children with symptomatic community-acquired urinary tract
      infection, without antimicrobial prophylaxis or recent prescription of
      antimicrobials, uropathogenic E coli strains resistant in vitro to ampicillin and
      cotrimoxazole were common. However, in vitro resistance to nitrofurantoin,
      coamoxiclav, and third-generation cephalosporins was uncommon.

PMID- 19108797
TI  - Eunice Kennedy Shriver National Institute of Child Health and Human Development
      Pediatric Formulation Initiative: selected reports from working groups.
AB  - BACKGROUND: The Pediatric Formulation Initiative (PFI) is a project of the Eunice
      Kennedy Shriver National Institute of Child Health and Human Development (NICHD).
      The PFI was established to address the issue of the lack of appropriate
      formulations in children and to use this activity as a means to improve pediatric
      formulations, as mandated by the Best Pharmaceuticals for Children Act of 2002
      and 2007. The PFI began in 2005 with the formation of 3 working groups
      Scientific, Economics, and Taste and Flavor. These groups began the process of
      identifying issues, gathering needed information, and considering possible ways
      to overcome barriers to the development of pediatric drug formulations.
      OBJECTIVE: The purpose of this supplement was to provide details of the working
      groups' activities through presentation of full-length articles. Also presented
      is an article that discusses the 2007 European Union (EU) regulation on medicinal
      products for pediatric use. METHODS: Information for this article was gathered
      from the proceedings of a PFI workshop, sponsored by the NICHD, that was held in
      Bethesda, Maryland, on December 6 and 7, 2005, as well as postworkshop
      discussions of the different working groups. RESULTS: The increased awareness
      that the majority of medications used today have not been labeled for use in
      children, and have not been tested to define safety, efficacy, and appropriate
      dosing, has led to the passage of legislation in the United States and in the EU
      to create incentives to stimulate the testing of drugs in this special
      population. It is imperative that the problems associated with the compounding
      and use of extemporaneous formulations as described in this supplement be
      addressed. Regulatory barriers to the availability of commercially developed
      pediatric formulations in different countries will need to be minimized or
      removed. New drug delivery systems will need to be tested and made available to
      pediatric patients. Further research in the mediators of bitter taste and study
      of taste blockers, as well as newer methods for taste testing in pediatrics,
      should be encouraged. An overarching goal for the future is addressing the
      economic barriers to develop appropriate pediatric dosage forms for drugs with
      limited market penetration. The lack of appropriate formulations is part of a
      larger problem that includes limited development and manufacture of medicines
      tailored for pediatric patients (particularly those affected by neglected
      diseases), insufficient investment in drug trials, and limited research on drug
      disposition in various pediatric populations worldwide. CONCLUSION: The solution
      to these issues will require alignment of vision and commitment as a global
      priority of policy makers, regulators, scientists, pharmaceutical sponsors,
      academic institutions, governments, and research foundations.

PMID- 19108798
TI  - Dosage form design and development.
AB  - BACKGROUND: Drugs must be properly formulated for administration to patients,
      regardless of age. Pediatric patients provide some additional challenges to the
      formulator in terms of compliance and therapeutic efficacy. Due to the lack of
      sufficient drug products for the pediatric population, the pharmaceutical
      industry and compounding pharmacies must develop and provide appropriate
      medications designed for children. OBJECTIVE: The purpose of this article was to
      review the physical, chemical, and biological characteristics of drug substances
      and pharmaceutical ingredients to be used in preparing a drug product. In
      addition, stability, appearance, palatability, flavoring, sweetening, coloring,
      preservation, packaging, and storage are discussed. METHODS: Information for the
      current article was gathered from a literature review; from presentations at
      professional and technical meetings; and from lectures, books, and publications
      of the author, as well as from his professional experience. Professional society
      meetings and standards-setting bodies were also used as a resource. RESULTS: The
      proper design and formulation of a dosage form requires consideration of the
      physical, chemical, and biological characteristics of all of the drug substances
      and pharmaceutical ingredients (excipients) to be used in fabricating the
      product. The drug and pharmaceutical materials utilized must be compatible and
      produce a drug product that is stable, efficacious, palatable, easy to
      administer, and well tolerated. Preformulation factors include physical
      properties such as particle size, crystalline structure, melting point,
      solubility, partition coefficient, dissolution, membrane permeability,
      dissociation constants, and drug stability. CONCLUSIONS: Successful development
      of a formulation includes multiple considerations involving the drug, excipients,
      compliance, storage, packaging, and stability, as well as patient considerations
      of taste, appearance, and palatability.

PMID- 19108799
TI  - Extemporaneous drug formulations.
AB  - BACKGROUND: Access to a special dosage form of a medication is essential when
      administration to infants and children and selected other populations is
      required. Some drugs necessary for pediatric patients are not commercially
      available in dosage forms appropriate for use in this population. These drugs may
      be prepared extemporaneously for use in individual patients. Physical and
      chemical properties of drugs and excipients should be considered when preparing
      extemporaneous formulations. These formulations, however, may lack studies to
      document stability, bioavailability, pharmacokinetics, pharmacodynamics,
      efficacy, and tolerability. OBJECTIVE: The goal of this article was to discuss
      factors involved in extemporaneous compounding of pediatric dosage forms.
      METHODS: The proceedings from a Pediatric Formulation Initiative workshop
      sponsored by the Eunice Kennedy Shriver National Institute of Child Health and
      Human Development, held December 6 and 7, 2005, in Bethesda, Maryland, were used
      as a source of information for this article. A literature search of PubMed/
      MEDLINE (1966-October 2008) was also conducted, using the search terms
      extemporaneous, drug formulations, and pediatric. RESULTS: Access to age
      appropriate drug formulations is critical to provide effective and well-tolerated
      medications to patients. There continues to be a need for extemporaneous
      formulations of brand and generic drugs for neonates, infants, and children.
      Potential solutions to current limitations include the need to develop a
      prioritized list of essential formulations, increased funding of research,
      dissemination of data, and monitoring of clinical effectiveness and tolerability
      during use in various age groups of pediatric patients and the sharing of these
      clinical experiences. CONCLUSION: To achieve desired therapeutic outcomes in
      pediatric patients, access to age-appropriate, stable, effective, and well
      tolerated drug formulations is essential.

PMID- 19108801
TI  - The economics of pediatric formulation development for off-patent drugs.
AB  - BACKGROUND: Many drugs currently used in children have never been adequately
      studied in rigorous scientific trials. Although these medications can still be
      prescribed in the pediatric setting, they are considered "off-label" because they
      are not specifically approved for use in children. The role of the Economics
      Working Group (EWG) within the Pediatric Formulation Initiative (PFI) of the
      Eunice Kennedy Shriver National Institute of Child Health and Human Development
      (NICHD) is to identify economic barriers and to propose possible mechanisms to
      create cost-effective and appropriately formulated products for off-patent
      pediatric drugs and to ensure their distribution and availability. OBJECTIVE: The
      purpose of this article was to briefly outline the EWG's considerations and
      recommendations on these topics. METHODS: Information for this article was
      gathered from the proceedings of a PFI workshop sponsored by the NICHD, held
      December 6 and 7, 2005, in Bethesda, Maryland. Other information was based on:
      the authors' unpublished and published research as well as personal communication
      with members of the EWG; a comprehensive search of Web sites, publications, and
      publicly accessible databases of the European Medicines Agency, the US Food and
      Drug Administration, the Agency for Healthcare Research and Quality, and the
      NICHD; and the databases and publications available from the Louis Lasagna
      Library of the Tufts Center for the Study of Drug Development (Boston,
      Massachusetts). RESULTS: The US Congress has attempted to remedy the lack of
      incentives to develop pediatric drugs by passing 2 key pieces of legislation.
      After >10 years, this US pediatric initiative has stimulated a great deal of
      pediatric drug research, and similar initiatives have been emulated in Europe and
      proposed in Japan. Although the initiative is generally considered successful in
      the United States, an incentive gap exists that still hinders pediatric drug
      development. It results from a series of factors, including: (1) a relatively
      small market size (<10% of the overall pharmaceutical market); (2) a predominance
      of off-patent drug use in the pediatric setting (perhaps as much as 70%); (3) no
      pediatric incentives for generic drug manufacturers; (4) fewer chronic illnesses
      in children than in adults; (5) a higher proportion of uninsured (mostly Medicaid
      recipients) and underinsured (many young families) patients; and (6) higher per
      patient costs as well as greater complexity of drug development. By understanding
      these barriers, more appropriate incentives can be generated by government, where
      these incentives are not inherently present in the market. CONCLUSIONS: The lack
      of child-friendly formulations leaves 40% of the world's population at increased
      risk for avoidable adverse events, suboptimal dosing, noncompliance, and lack of
      access to new medicines. Incentive programs are the surest and least expensive
      means to overcome the tendency of "big pharma" to overlook the pediatric market
      as too small, and of start-up and specialty companies to consider it too
      problematic. Given the relatively lengthy period required to build product
      development infrastructure, these several decades-when market growth potential,
      demographics, and public health considerations are aligned in favor of pediatric
      formulation needs-are a critical time frame for creating a private and public
      sector environment to support this effort.

PMID- 19108800
TI  - Optimizing oral medications for children.
AB  - BACKGROUND: Active pharmaceutical ingredients that taste bitter and/or irritate
      the mouth and throat are aversive to children as well as many adults. Effective
      methods of avoiding unpleasant tastes for adults (eg, encapsulating the medicine
      in pill, capsule, or tablet form) are problematic because many children cannot or
      will not swallow these. The unpalatable flavor of the medicine can thwart the
      benefits of even the most powerful of drugs. Failure to consume medication may do
      the child harm and can even be life-threatening. OBJECTIVES: This article
      provides an overview of the current knowledge of the sensory capabilities and
      preferences of children as it relates to flavor, defined here as the combined
      input of taste, smell, and chemical irritation. The methods used to evaluate
      flavor perception in children are reviewed. Recent scientific advances are
      summarized that shed light on why the bitter taste of oral pharmaceuticals is an
      ongoing formulation problem and how discoveries of novel flavor molecules and
      modulators of bitter tastes hold considerable promise for the future. Alternative
      methods for evaluation of the palatability of medicines are described. METHODS:
      The Eunice Kennedy Shriver National Institute of Child Health and Human
      Development sponsored a Pediatric Formulation Initiative workshop on December 6
      and 7, 2005, in Bethesda, Maryland. Information for this article was gathered
      from literature reviews that were then discussed during this workshop as well as
      during several conference calls with the Taste and Flavor Working Group members.
      Terms for the MEDLINE search (1970-2007) included infant, children, taste,
      olfaction/smell, flavor, chemical senses, palatability, sensory testing,
      pharmaceutical, and medicines. RESULTS: Children have well-developed sensory
      systems for detecting tastes, smells, and chemical irritants, and their rejection
      of unpalatable medications is a reflection of their basic biology. Sugars, salt,
      and other substances reportedly reduce the bitterness of several pharmaceuticals.
      Adding pleasant flavor volatiles such as bubble gum may help induce children to
      consume a medicine, but such volatile compounds are not effective in suppressing
      the strong bitter tastes associated with some medications. Also, because
      individual experiences and culture mainly determine which odors are attractive, a
      universally appealing volatile flavoring agent may be difficult to identify.
      Sensory panelists who are sensitive to the pediatric palate, which is different
      from adults, and new techniques involving animal models, isolated parts of the
      receptor cells, and even electronic devices that detect taste and flavor are
      among the tools that may be used to evaluate the palatability of medications and
      predict compliance among pediatric populations. CONCLUSIONS: Although there are
      no easy solutions to this dilemma, children's acceptance of many medicines can be
      improved by applying the knowledge gleaned from basic research in the chemical
      senses. Further development and validation of sensory methods will provide a
      better understanding of the sensory world of the child. This understanding,
      combined with new technologies and results of animal model studies, will enhance
      drug acceptance and compliance in pediatric populations. A better understanding
      of the scientific basis for distaste and how to ameliorate it is a public health
      priority.

PMID- 19108802
TI  - European perspectives on pediatric formulations.
AB  - BACKGROUND: The 2007 European Union (EU) regulation on medicinal products for
      pediatric use may change the present unsatisfying situation in the EU by
      stimulating research and development of medicines for use in children through
      rewards and incentives. OBJECTIVES: This commentary reflects on the new EU
      regulations and guidelines, with special attention paid to the impact on
      pediatric formulation science. The focus of this article is on the EU perspective
      for pediatric formulations and highlights the differences compared with the
      pediatric drug formulation situation in the United States. METHODS: Materials for
      this article were gathered during a literature search of MEDLINE and Chemical
      Abstracts (1970-October 2008) using the following terms: paediatric/pediatric
      drug formulations, age-appropriate dosage forms, child-appropriate medicines, and
      paediatric/pediatric regulation. RESULTS: Since the EU legislation on medicines
      for children came into force in 2007, a great emphasis has been placed on
      creating new organizations, scientific networks, and programs dealing with
      pediatric medicines and child-appropriate drug formulations. Although the US
      legislation was an appropriate model, the EU introduced some novel measures to
      improve the current situation, such as the Paediatric Investigation Plan and the
      Paediatric Use Marketing Authorisation. For globally operating pharmaceutical
      companies, the peculiarities of the European market have a strong impact on their
      product development strategies. Because the European approach demands early
      investigations into drug formulations for children, various issues must be
      resolved, including the following: choosing formulations for each age group,
      determining which excipients may be used in the formulation and which delivery
      device is appropriate, and predicting the taste sensation of an oral formulation.
      Numerous initiatives and networks are evolving in Europe. An important future
      task will be the coordination of these activities and the linking to other groups
      working on pediatric formulations outside the EU. CONCLUSION: Similar to the
      research in pediatric drug formulations that was stimulated by the US legislation
      and incentives of the last decade, the 2007 EU legislation promises improvements
      in the availability of child-appropriate drugs in Europe.

PMID- 19108803
TI  - Consumer medication management and error.

PMID- 19108804
TI  - Assessing prescriptions for statins in ambulatory diabetic patients in the United
      States: a national, cross-sectional study.
AB  - BACKGROUND: Diabetes mellitus affects >20 million people in the United States
      each year, and >4000 new cases are diagnosed daily. OBJECTIVE: This study
      assessed the prescription of statin medications in the ambulatory setting in US
      diabetic patients. METHODS: We used data from the 2002 through 2004 National
      Ambulatory Medical Care Survey and National Hospital Ambulatory Medical Care
      Survey. All ambulatory medical visits associated with a diabetes diagnosis by the
      International Classification of Diseases, Ninth Revision, Clinical Modification
      were included. Prescriptions for statin medications were determined by searching
      each ambulatory visit for relevant drug names (trade and generic). Demographic
      characteristics were assessed, including survey year, sex, age group, race,
      ethnicity, payment type, region of the country, and physician's specialty and
      degree. Analyses used sample weights to calculate national estimates. RESULTS:
      From 2002 to 2004, 10,046 (unweighted) ambulatory visits were made by diabetic
      patients, representing a weighted national estimate of approximately 153 million
      visits. A statin prescription was associated with 21.1% of all diabetic visits
      and 14.1% of those without a hyperlipidemia-related diagnosis. Diabetic men were
      more likely than diabetic women to be given a prescription for a statin (odds
      ratio [OR], 1.38; 95% CI, 1.09-1.73). Compared with diabetic patients treated in
      2002, those treated in 2003 and 2004 were more likely to be prescribed statin
      therapy (2003 OR, 1.51; 95% CI, 1.02-2.24; 2004 OR, 1.48; 95% CI, 1.03-2.15).
      Compared with diabetic patients aged 45 to 64 years, those in younger age groups
      were less likely to be given a statin prescription (1-24 years OR, 0.10; 95% CI,
      0.01-0.84; 25-44 years OR, 0.48; 95% CI, 0.31-0.74), and those aged 65 to 74
      years were more likely to be given a statin (OR, 1.38; 95% CI, 1.01-1.90). No
      differences were noted for diabetic patients aged > or = 75 years. CONCLUSIONS:
      From 2002 through 2004, <25% of the ambulatory medical visits by diabetic
      patients in the United States were associated with a statin prescription. Male
      sex and age up to 75 years had an increased association with statin prescription.
      Additional study is anticipated to assess changes in statin use in diabetic
      patients in the United States as updated treatment guidelines are released.

PMID- 19108806
TI  - Doctor atomic and doctor genomic.

PMID- 19108805
TI  - Long-term persistence with statin treatment in a not-for-profit health
      maintenance organization: a population-based retrospective cohort study in
      Israel.
AB  - BACKGROUND: Although discontinuing lipid-lowering treatment can cause preventable
      morbidity, previously published reports have indicated considerable variability
      in persistence with statin use. In general, such reports have been limited by
      short follow-up periods and modest study populations. OBJECTIVES: The aims of
      this study were to assess long-term persistence with statins and to identify the
      sociodemographic, clinical, and pharmacotherapy-related factors associated with
      long-term persistence with statin treatment in first-time users in Israel.
      METHODS: This retrospective cohort study used data from adult enrollees of a not
      for-profit health maintenance organization and from death certificates in Israel.
      Eligible patients initiated statin treatment between 1998 and 2006. Persistence
      was assessed separately in patients with no indication of a cardiovascular
      disease (primary prevention) or coronary artery disease (secondary prevention).
      Treatment persistence and proportion of days covered (PDC) were measured using
      the interval between the date of the first prescription dispensation (index date)
      and the point of discontinuation. RESULTS: Data from 229,918 patients were
      included (primary prevention, 136,052; secondary prevention, 93,866). The PDC was
      significantly higher in the secondary-prevention group compared with the primary
      prevention group (59% vs 45%; P < 0.001). In both cohorts, persistence
      continually diminished from the index date through follow-up, with > or = 75% of
      patients discontinuing statin therapy by 2 years. Baseline predictors of
      discontinuation of statin treatment included younger age, female sex, lower
      socioeconomic status (SES), absence of diabetes or hypertension, no concurrent
      use of beta-blockers or angiotensin-converting enzyme inhibitors, and less health
      service utilization. New immigrants and patients in the primary-prevention group
      who had a baseline low-density lipoprotein cholesterol concentration <130 mg/dL
      were at increased risk for treatment discontinuation. CONCLUSION: In this study
      in these patients receiving first-time statin treatment in Israel, we found poor
      persistence with statins among both the primary- and secondary-prevention
      cohorts, especially among new immigrants and patients with low SES despite low
      out-of-pocket prescription costs and free access to health services.

PMID- 19108807
TI  - Reshaped destinies: confronting our human future the need for and promise of an
      interdisciplinary colloquium.
AB  - The genomic revolution is bringing with it simultaneous needs for both scientists
      and nonscientists to understand and assess, in an unvarnished and nonjudgmental
      way, the implications of genometry. This is the field of science and technology
      that is taking the genetic code and what we have learned from its secrets, and
      reshaping our individual and collective human destinies. Together with the editor
      in-chief of Gender Medicine, the authors propose an interdisciplinary group
      populated by those in science, law, ethics, social policy, and the interested
      public-to observe, understand, and disseminate information about what is
      occurring in the fields of biology and chemistry that is the driving force of the
      genomic revolution. This article discusses the background to the Redefined
      Destinies Colloquium (RDC) and summarizes 4 of the topics the RDC is studying.

PMID- 19108808
TI  - The relationship of body fat to metabolic disease: influence of sex and
      ethnicity.
AB  - Clinical investigations designed to determine risk profiles for the development
      of cardiovascular disease (CVD) and type 2 diabetes mellitus (DM) are usually
      performed in homogenous populations and often focus on body mass index (BMI),
      waist circumference (WC), and fasting triglyceride (TG) levels. However, there
      are major ethnic differences in the relationship of these risk factors to
      outcomes. For example, the BMI risk threshold may be higher in blacks than in
      whites and higher in women than in men. Furthermore, a WC that predicts an obese
      BMI in white women only predicts a BMI in the overweight category in black women.
      In addition, overweight black men have a greater risk of developing type 2 DM
      than do overweight black women. Although TG levels are excellent predictors of
      insulin resistance in whites, they are not effective markers of insulin
      resistance in blacks. Among the criteria sets currently available to predict the
      development of CVD and type 2 DM, the most well known is the metabolic syndrome.
      The metabolic syndrome has 5 criteria: central obesity, hypertriglyceridemia, low
      high-density lipoprotein (HDL) levels, fasting hyperglycemia, and hypertension.
      To make the diagnosis of the metabolic syndrome, 3 of the 5 factors must be
      present. For central obesity and low HDL, the metabolic syndrome guidelines are
      sex specific. Diagnostic guidelines should also take ethnic differences into
      account, particularly in the diagnosis of central obesity and
      hypertriglyceridemia.

PMID- 19108809
TI  - The metabolic syndrome: racist, sexist, or both?

PMID- 19108810
TI  - Descriptive analysis of concomitant prescription medication patterns from 1999 to
      2004 among US women receiving daily or weekly oral bisphosphonate therapy.
AB  - BACKGROUND: To improve medication-taking behavior, it is important to identify
      factors that may contribute to suboptimal compliance and persistence with
      osteoporosis medications. OBJECTIVE: The purpose of this descriptive analysis was
      to identify concurrent prescription medication use (number and type) among women
      receiving daily or weekly oral bisphosphonate therapy. METHODS: Patient
      prescription data were collected from November 1999 to June 2004 from a US
      patient claims database accessed through Wolters Kluwer Health (formerly NDC
      Health), which represents >65 million patients annually. Women aged >or=50 years
      who were receiving daily or weekly oral bisphosphonate medication during the
      study months were included. Concomitant medications were defined based on >or=14
      days of prescription supply in the same month as bisphosphonate therapy. Data
      were examined to determine the frequency with which certain drugs and drug
      classes were prescribed concomitantly with bisphosphonates. Each study month was
      treated independently to assess concomitant medication use. RESULTS: Over the
      study period, the number of female bisphosphonate recipients in the database
      increased from 78,909 to 250,286. At the end of the study, 16.2%, 12.2%, 8.7%,
      and 19.1% of bisphosphonate recipients were prescribed 3, 4, 5, or >or=6
      concomitant medications, respectively. The most commonly prescribed concomitant
      drug classes were cholesterol reducers, diuretics, beta-blockers, calcium channel
      blockers, synthetic thyroid hormones, angiotensin-converting enzyme inhibitors,
      systemic analgesics/anti-inflammatory drugs, and antispasmodics/antisecretory
      drugs. From July 2001 until the end of the study, the number of concomitant
      medications was higher for women receiving daily bisphosphonates than for those
      receiving weekly bisphosphonates, 4.16 versus 3.77 as of June 2004. In addition,
      the mean number of concomitant medications prescribed increased with age: in the
      aged 50 to 64 years cohort, the aged 65 to 74 years cohort, and the aged >or=75
      years cohort, the mean number was 3.09, 3.62, and 3.97, respectively, as of June
      2004. CONCLUSION: This analysis suggests that women prescribed bisphosphonates
      have a high medication burden, with the majority of patients (56%) taking >or=3
      concomitant prescription medications.

PMID- 19108811
TI  - Gender-specific differences in bladder cancer: a retrospective analysis.
AB  - BACKGROUND: A higher incidence of bladder cancer has been reported in men
      compared with women. Clinical gender differences have been observed but are less
      well described. OBJECTIVE: This retrospective analysis further examines clinical
      differences in the development and manifestation of bladder cancer between men
      and women. METHODS: Consecutive male and female patients with bladder cancer
      treated between 1969 and 1997 at a single center (University Hospital of
      Innsbruck, Innsbruck, Austria) were included in the study. Patient
      characteristics regarding age, tumor classification, localization, and recurrence
      were compared between male and female patients. Statistical analysis was
      conducted using the t test, the chi(2) test, and the Kaplan-Meier method, with
      the log-rank test for subgroup analysis. RESULTS: In the 1,269 patients (876 men,
      393 women) who were examined, 1,744 tumors were found. The male-to-female bladder
      cancer incidence ratio was 2.2:1. Tumors were diagnosed at a significantly
      younger age in men than in women (mean age: 62 years vs 67 years, respectively; P
      < 0.001). No difference in the histology of tumors was observed between the
      sexes. Muscle-invasive tumors more frequently occurred in men than in women
      (39.8% vs 34.5%; P = NS). In men compared with women, primary tumors were more
      aggressive (grade 2, 36.6% vs 28.2%; P < 0.001) and tumor recurrences were more
      invasive (59.0% vs 57.8%; P = NS). Tumors were more often located in the urethra
      in men than in women (43 [3.4%] vs 9 [1.8%]; P = 0.034), the trigonum (246
      [19.8%] vs 75 [14.9%]; P < 0.001), and the bladder dome or vault (128 [10.3%] vs
      37 [7.4%]; P = 0.015). Generally, no difference in survival rate was observed
      between the sexes; only in the subgroup of muscle-invasive tumors (n = 455) did
      women have a worse overall survival rate than did men (P = 0.022). CONCLUSIONS:
      Clinical gender differences in bladder cancer appear to have a higher incidence
      in men than in women. In this analysis, women were older at the age of detection,
      but had less-invasive and less-aggressive tumors than did men. However, women
      with muscle-invasive disease had a worse overall survival rate than did men in
      the same subset.

PMID- 19108812
TI  - Impact of an integrated service system on client outcomes by gender in a national
      sample of a mentally ill homeless population.
AB  - BACKGROUND: Homeless populations with concurrent mental illness have a complex
      array of service needs that are often addressed in a haphazard or uncoordinated
      manner. Information is lacking about the effectiveness of programs and public
      policy in women who are both homeless and mentally ill. OBJECTIVE: This study
      assessed the impact of gender on the outcomes of a multisite public policy
      intervention that implemented components of an integrated service delivery system
      to address the needs of mentally ill homeless men and women. METHODS: A secondary
      analysis was performed using longitudinal data obtained from homeless men and
      women in the Access to Community Care and Effective Services and Supports
      prospective study, which was conducted at 18 sites across the United States.
      Outcome data from baseline, 3, 12, and 18 months across 5 annual cohorts were
      analyzed to determine the impact of gender on 6 clinical outcomes, including days
      of housing, relationships, victimization, social support, alcohol use, and drug
      use, in homeless men and women with mental illness. The analysis plan included
      multilevel modeling of longitudinal data. RESULTS: Data were analyzed from a
      total of 7,229 participants, including 4,502 men (62%)) (mean age, 38.2 years)
      and 2,727 women (38%) (mean age, 37.2 years). After 18 months of follow-up, women
      had significantly better outcomes in terms of family relationships (estimated
      mean score increased 0.100), victimization (score decreased 0.164), and social
      support (score increased 0.363) than did men (all, P < 0.001). Being accompanied
      by children was significantly associated with less change in drug use among women
      compared with men (P < 0.01). These outcomes were the same across all 18 program
      sites. CONCLUSION: Although the addition of services for the homeless in
      conjunction with clinical and support services offered by case managers had
      generally positive effects in this study's population, a gender-specific
      substance abuse treatment intervention should also be included in a comprehensive
      program for homeless women with mental illness.

PMID- 19108813
TI  - Retrospective case evaluation of gender differences in sports injuries in a
      Japanese sports medicine clinic.
AB  - BACKGROUND: Although both gender- and sports-specific injuries exist among
      athletes, gender differences in the types of injuries caused by sports
      activities, except for anterior cruciate ligament (ACL) injury and anterior knee
      pain, are not well established. OBJECTIVE: An observational study with a
      retrospective case-series design was conducted to investigate gender-specific
      differences in the types of injuries sustained while engaging in sports
      activities common to both males and females. METHODS: We analyzed injuries
      sustained during sports activities including basketball, volleyball, tennis,
      skiing, track and field, and swimming, using data on age, sex, sports activities,
      activity levels, and sports injuries that had been computerized at our sports
      medicine (orthopedics) clinic. Inclusion criteria were sports activities that had
      a record of >100 injuries in total and athletes aged <50 years who were engaging
      in only 1 sports activity. We determined the absolute number of patients in each
      category and their percentage (proportion) of our cohort. The proportions of
      common injuries caused by sports activities were investigated, and gender
      specific differences in the types of common injuries caused by sports activities
      were clarified. The Fisher exact test was used to determine the significance (P <
      0.01) of the gender-specific differences in the types of sports injuries.
      RESULTS: According to our database, during the 14-year period between October
      1992 and December 2006, a total of 2,989 athletes (1,624 males and 1,365 females)
      aged <50 years who engaged in 1 of the 6 sports activities described consulted
      our sports medicine clinic. The most common sports injuries were ACL injury
      (14.3%) and knee pain (13.7%), followed by ankle sprain (9.4%), lumbar disc
      disease (7.0%), meniscus injury (5.1%), stress fracture (2.9%), low back pain
      (2.5%), patellar tendinitis (2.1%), injury of the medial collateral ligament of
      the knee (2.0%), lumbar spondylolysis (1.7%), and muscle strain (1.5%). Among
      these 11 types of sports injuries, a significantly higher proportion of females
      who engaged in basketball (24.4% vs 10.5%), volleyball (20.5% vs 4.5%), or skiing
      (41.4% vs 26.5%) presented with an ACL injury, compared with their male
      counterparts (all, P < 0.001). There was also a significantly higher proportion
      of females than of males among the track and field athletes who presented with
      stress fractures (18.7% vs 3.9%; P < 0.001). CONCLUSION: The findings of this
      retrospective study suggest that there are gender-specific differences in the
      types of injuries sustained during sports activities.

PMID- 19108814
TI  - Gender- and age-related outcomes of cardiac resynchronization therapy: a pilot
      observational study.
AB  - BACKGROUND: Cardiac resynchronization therapy (CRT) has been reported to improve
      clinical status and survival, and shorten hospitalization rates, in patients with
      heart failure (HF). However, questions remain regarding the success of CRT in
      different subgroups of patients with HE. OBJECTIVE: We assessed whether CRT
      response was related to gender or age in patients with HE. METHODS: In a
      longitudinal observational study, patients with severe HF (New York Heart
      Association [NYHA] class III or IV, left ventricular ejection fraction [LVEF]
      <or=35%, and QRS duration >120 ms with left bundle branch block configuration)
      were enrolled. Clinical electrophysiologic and echocardiographic evaluations were
      performed before, and 3 and 6 months after, CRT implantation. RESULTS: A total of
      65 Iranian patients (50 men, 15 women; mean [SD] age, 60.3 [10.3] years; baseline
      NYHA class, 3.1 [0.36]; QRS duration, 144 [14] ms; LVEF, 21% [7.3%]; left
      ventricular end-diastolic diameter (LVEDD), 6.8 [0.56] mm) were evaluated. NYHA
      class, QRS duration, LVEF, and LVEDD were significantly improved at 3- and 6
      month follow-ups both in patients aged <or=60 years and in those aged >60 years
      (P < 0.001, except for aged <or=60 years after 3-month follow-up [P = 0.002]).
      All these parameters were significantly improved in men at 3- and 6-month follow
      ups (P < 0.001). NYHA class (P = 0.002), QRS duration (P = 0.001), LVEF (P =
      0.013 at 3 months and <0.001 at 6 months), and LVEDD (P = 0.007 at 3 months and
      <0.001 at 6 months) also were significantly improved in women. At 3- and 6-month
      follow-ups, there were no significant differences in improvement of these factors
      between the 2 age groups of patients. CONCLUSION: CRT response in these patients
      with HF did not appear to be gender or age related at 3- and 6-month follow-ups
      in this small observational study. Confirmation of these findings by larger
      studies is needed.

PMID- 19108815
TI  - Estrogen and progesterone affect responses to malaria infection in female C57BL/6
      mice.
AB  - BACKGROUND: Previous data from our laboratory suggest that gonadally intact
      C57BL/6 male mice are more likely than their female counterparts to die from
      Plasmodium chabaudi infection, to recover more slowly from weight loss and
      hematocrit loss, and to have reduced interferon-gamma (IFN-gamma) and interleukin
      10 (IL-10) responses. Removal of the ovaries, and hence, the primary production
      of sex steroids in females, reverses these differences. OBJECTIVE: We
      hypothesized that sex differences in response to P chabaudi may be mediated by
      differential synthesis of IFN-gamma and IL-10 that is influenced by estrogen,
      progesterone, or both. METHODS: C57BL/6 female mice (n = 200; n = 10/time
      point/treatment/experiment) were ovariectomized and implanted with a 21-day
      controlled-release pellet containing either 0.1 mg of 17beta-estradiol (E(2)), 10
      mg of progesterone (P(4)), 0.1 mg of E(2) plus 10 mg of P(4), or cholesterol
      (placebo). Females were inoculated with 10(6)P chabaudi-infected erythrocytes.
      Body mass, body temperature, hematocrit, parasitemia, cytokine production, and
      antibody responses were monitored 0, 3, 5, 7, 10, 14, and 21 days
      postinoculation. RESULTS: Administration of E(2), either alone or in combination
      with P(4), mitigated infection-induced weight loss, hematocrit loss, and
      hypothermia, compared with females receiving placebo pellets (P < 0.05 in each
      case). Hormone treatment did not affect levels of parasitemia. Females
      administered E(2) alone or in combination with P(4) produced 4 to 7 times higher
      IFN-gamma and IL-10 during peak parasitemia than did females implanted with
      pellets containing either P(4) alone or placebo (P < 0.05 in each case). Exposure
      to E(2), either alone or in combination with P(4), increased anti-P chabaudi
      immunoglobulin G (IgG1) responses and the ratio of IgG1 to IgG2c (P < 0.05 in
      each case). CONCLUSION: This animal study suggests that physiological levels of
      estrogen, rather than progesterone, enhance immunity and, possibly, protect
      females from disease symptoms during malaria infection.

PMID- 19108816
TI  - Inhibitory effects of progesterone differ in dendritic cells from female and male
      rodents.
AB  - BACKGROUND: Steroid hormones, such as progesterone, are known to have
      immunomodulatory effects. Our research group previously reported direct effects
      of progesterone on dendritic cells (DCs) from female rodents. Primarily affecting
      mature DC function, progesterone effects included inhibition of proinflammatory
      cytokine secretion, downregulation of cell surface marker (major
      histocompatibility complex class II, CD80) expression, and decreased T-cell
      proliferative capacity, and were likely mediated through progesterone receptor
      (PR) because the PR antagonist RU486 reversed these effects. OBJECTIVE: The goal
      of this study was to assess differences in response to progesterone by DCs from
      female and male rodents. METHODS: Using real-time reverse-transcriptase
      polymerase chain reaction, transcriptional expression of steroid hormone
      receptors was measured in immature bone marrow-derived DCs (BMDCs) from male and
      female rats. Expression of steroid hormone receptor protein was also assessed in
      these cells using flow cytometry and fluorescence microscopy. To evaluate
      functional differences between BMDCs from female and male rats in response to the
      steroid hormone progesterone, levels of secreted cytokines were measured using
      enzyme-linked immunosorbent assay. RESULTS: Higher numbers of immature BMDCs from
      males expressed glucocorticoid receptor (GR) and androgen receptor (AR) proteins
      compared with females (males vs females, mean [SD]: GR = 68.75 [7.27] vs 43.61
      [13.97], P = NS; AR = 75.99 [15.38] vs 8.25 [1.88], P = 0.002), whereas higher
      numbers of immature BMDCs from females expressed PR protein compared with males
      (females vs males: PR = 74.19 [12.11] vs 14.14 [4.55], P = 0.043). These
      differences were not found at the level of transcription (females vs males: GR =
      0.088 vs 0.073, P = NS; AR = 0.076 vs 0.069, P = NS; PR = 0.075 vs 0.065, P =
      NS). Compared with those from females, mature BMDCs from males produced higher
      quantities of cytokines (tumor necrosis factor-alpha [TNF-alpha], interleukin
      [IL]-1beta, IL-10) (females vs males: TNF-alpha = 920.0 [79.25] vs 1100.61
      [107.97], P = NS; IL-1beta = 146.60 [38.04] vs 191.10 [10.47], P = NS; IL-10 =
      167.25 [4.50] vs 206.15 [23.48], P = NS). Conversely, BMDCs from females were
      more sensitive to progesterone, as indicated by a more dramatic reduction in
      proinflammatory cytokine secretion (females vs males, highest concentration of
      progesterone: TNF-alpha = 268.94 [28.59] vs 589.91 [100.98], P = 0.04; IL-1beta =
      119.50 [10.32] vs 154.35 [6.22], P = NS). CONCLUSIONS: These findings suggest
      that progesterone effects on DCs in rodents may be more pronounced in females
      than in males, and this is likely due to differences in PR protein expression.
      Our observations may help elucidate disparities in the incidence and severity of
      autoimmune disorders between females and males, and the role specific steroid
      hormones play in regulating immune responses.

PMID- 19108817
TI  - A history of childhood behavioral inhibition and enhanced response monitoring in
      adolescence are linked to clinical anxiety.
AB  - BACKGROUND: Behaviorally inhibited (BI) children who also exhibit enhanced
      response monitoring might be at particularly high risk for anxiety disorders. The
      current study tests the hypothesis that response monitoring, as manifest in the
      error-related negativity (ERN), moderates the association between BI and anxiety.
      METHODS: Participants (n=113; 73 male) assessed for early-childhood BI were re
      assessed as adolescents with a clinical interview and a flanker paradigm that
      generated behavioral data and event-related potentials (ERPs). Risk for anxiety
      disorders in adolescents was examined as a function of childhood-BI status and
      adolescent performance on the flanker paradigm. RESULTS: Adolescents with
      childhood BI displayed ERP evidence of enhanced response monitoring, manifest as
      large ERNs. The ERN moderated the relationship between early BI and later
      clinically significant disorders. CONCLUSIONS: Physiological measures of response
      monitoring might moderate associations between early-childhood BI and risk for
      psychopathology. The subset of children with BI and enhanced response monitoring
      might face greater risk for later-life clinical anxiety than children with either
      BI or enhanced response monitoring alone.

PMID- 19108818
TI  - Effect of annealing and pressure on microstructure of cornstarches with different
      amylose/amylopectin ratios.
AB  - This work focuses on the effect of annealing and pressure on microstructures of
      starch, in particular the crystal structure and crystallinity to further explore
      the mechanisms of annealing and pressure treatment. Cornstarches with different
      amylose/amylopectin ratios were used as model materials. Since the samples
      covered both A-type (high amylopectin starch: waxy and maize) and B-type (high
      amylose starch: G50 and G80) crystals, the results can be used to clarify some
      previous confusion. The effect of annealing and pressure on the crystallinity and
      double helices were investigated by X-ray diffraction (XRD) and (13)C CP/MAS NMR
      spectroscopy. The crystal form of various starches remained unchanged after
      annealing and pressure treatment. XRD detection showed that the relative
      crystallinity (RC) of high amylopectin starches was increased slightly after
      annealing, while the RC of high amylose-rich starches remained unchanged. NMR
      measurement supported the XRD results. The increase can be explained by the chain
      relaxation. XRD results also indicated that some of the fixed region in
      crystallinity was susceptible to outside forces. The effect of annealing and
      pressure on starch gelatinization temperature and enthalpy are used to explore
      the mechanisms.

PMID- 19108819
TI  - Examination of the effect of structural variation on the N-glycosidic torsion
      (PhiN) among N-(beta-D-glycopyranosyl)acetamido and propionamido derivatives of
      monosaccharides based on crystallography and quantum chemical calculations.
AB  - GlcNAcbetaAsn linkage is conserved in the N-glycoproteins of all eukaryotes. l
      Glutamine (Gln), which is a one carbon higher homolog of Asn, is never
      glycosylated. X-ray crystallographic study of several beta-1-N-acetamido- and
      propionamido derivatives of monosaccharides has earlier shown that the N
      glycosidic torsion, Phi(N), is influenced to a larger extent by the structural
      variation of the sugar part than that of the aglycon moiety. In order to examine
      the influence of the carbohydrate pendent groups on the conformational preference
      of the N-glycosidic linkage with respect to Phi(N,) several models and analogs
      with gluco and manno configuration have been studied in the present work by
      computational chemistry. The crystal structure of XylbetaNHPr is reported here
      and its molecular packing compared with related analogs. The conjunction of
      combining Crystallographic and computational studies allows to demonstrate the
      strong influence that the group at C2, and environmental factors particularly
      inter- and intramolecular interactions involving regular hydrogen bonds and the
      weak C-H...O contacts, have on the energy preference of the Phi(N) torsion angle.

PMID- 19108820
TI  - Beginning readers activate semantics from sub-word orthography.
AB  - Two experiments assessed whether 7-year-old children activate semantic
      information from sub-word orthography. Children made category decisions to
      visually-presented words, some of which contained an embedded word (e.g., hip in
      ship). In Experiment 1 children were slower and less accurate to classify words
      if they contained an embedded word related in meaning to the category (e.g.,
      slower to reject ship as a 'body part' than an 'animal'), especially when the
      embedded word was higher in frequency than the carrier word. This demonstrates
      that young children activate semantic information from sub-word orthographic
      representations, and that they do so from the relatively early stages of learning
      to read. Experiment 2 replicated this effect. Furthermore, we observed semantic
      interference regardless of whether the embedded word shared its pronunciation
      with the carrier (e.g., the hip in ship) or not (e.g., the crow in crown), and
      regardless of its position within the carrier, suggesting that interference was
      not dependent on phonological mediation. These findings show that by 7-years-of
      age, children have begun to establish an orthographic system that is capable of
      activating sub-word orthographic patterns, strong enough to connect with meaning,
      when reading words silently.

PMID- 19108821
TI  - Indoor contaminants from newspapers: VOCs emissions in newspaper stands.
AB  - Mean volatile organic compound (VOC) concentrations in 16 newspaper stands and in
      two printing shops were monitored for the purpose of quantifying the various VOCs
      in these areas and to relate the results. In each site halogenated, oxygenated,
      aliphatic, and aromatic compounds were monitored during one workweek. They were
      sampled with diffusive samplers for thermal desorption and analysed by GC-MS. The
      results showed that in all newspaper stands the indoor levels of toluene were
      much higher than the outdoor levels; some sites had toluene indoor concentrations
      100 times higher than their correspondent outdoor levels. The investigations in
      two printing shops confirmed that newspapers, in particular the inks, are the
      main sources of toluene in the newspaper stands.

PMID- 19108822
TI  - True ovarian volume is underestimated by two-dimensional transvaginal ultrasound
      measurement.
AB  - OBJECTIVE: To investigate a possible difference between true ovarian volume and
      ovarian volume estimated with two-dimensional (2D) transvaginal ultrasound.
      DESIGN: Prospective clinical and laboratory study. SETTING: University hospital
      research laboratory. PATIENT(S): Premenopausal girls and women from three Danish
      national fertility centers (A: n = 42; B: n = 6; C: n = 18), who had one entire
      ovary removed for cryopreservation of ovarian cortex. INTERVENTION(S):
      Transvaginal 2D ultrasound measurement of ovarian volume before oophorectomy.
      True ovarian volume was obtained by weighing the ovary. MAIN OUTCOME MEASURE(S):
      Ovarian volume estimated by weight and ultrasound. RESULT(S): Ovarian tissue
      density was 1.00 g/mL. Mean ovarian volume by ultrasound vs. weight in the three
      groups was as follows: A: 6.3 mL vs. 7.8 mL; B: 5.4 mL vs. 6.8 mL; and C: 2.8 mL
      vs. 6.1 ml. Ovarian volume obtained by ultrasound was at least 27% smaller than
      the true ovarian volume. CONCLUSION(S): Ovarian volume was severely
      underestimated by transvaginal 2D ultrasound measurement.

PMID- 19108823
TI  - Comparison of in vitro fertilization versus intracytoplasmic sperm injection in
      extremely low oocyte retrieval cycles.
AB  - OBJECTIVE: To compare the results of IVF and intracytoplasmic sperm injection
      (ICSI) in extremely low oocyte retrieval cycles. DESIGN: Case-control study.
      SETTING: An IVF laboratory in a university hospital in Taiwan. PATIENT(S):
      Between January 2003 and December 2007, infertile couples with one, two, or three
      oocytes per retrieval were divided into two groups: 56 IVF cycles based on 28
      demographic characteristics from the ICSI group. INTERVENTION(S): None. MAIN
      OUTCOME MEASURE(S): Fertilization rate, cycle cancellation rate, clinical
      pregnancy rate, and implantation rate per transfer. RESULT(S): The normal
      fertilization rate was significantly higher after ICSI than after standard IVF
      (86.4% vs. 69.3%). The cycle cancellation and complete fertilization failure
      rates were comparable between the two groups. The clinical pregnancy rate per
      transfer (38.5% vs. 21.6%), implantation rate (23.5% vs. 11.1%), and live birth
      rate per transfer (30.8% vs. 13.7%) had a favorable trend, but no statistically
      significant differences, in the ICSI group compared with the IVF group.
      CONCLUSION(S): A higher normal fertilization rate can be achieved by ICSI in
      comparison with conventional IVF in extremely low oocyte retrieval cycles.

PMID- 19108824
TI  - Effect of macroscopic or microscopic blood and mucus on the success rates of
      embryo transfers.
AB  - OBJECTIVE: To assess the effect of microscopic and macroscopic contamination of
      embryo transfer (ET) catheters with blood or mucus on in vitro fertilization
      (IVF)-ET success rates. DESIGN: Retrospective cohort study. SETTING: Infertility
      practice in teaching community hospital. PATIENT(S): Four hundred seventy
      patients undergoing IVF-ET. INTERVENTION(S): Controlled ovarian hyperstimulation
      and IVF-ET. MAIN OUTCOME MEASURE(S): Implantation rate (IR) and clinical
      pregnancy rate (CPR). RESULT(S): The IR and CPR of IVF-ETs were comparable
      regardless of the presence (26.59% and 48.78%, respectively) or absence (23.49%
      and 44.44%, respectively) of any type of contamination. Even when analyzing
      specific contamination categories (i.e., macroscopic blood, microscopic blood on
      the outer catheter, microscopic blood on the inner catheter, blood anywhere
      without mucus, mucus only, or blood and mucus combined), there was no statistical
      significance in IR (range: 21.17% to 26.69%) or CPR (range: 32.69% to 49.5%).
      CONCLUSION(S): In general, IR and CPR appear to be unaffected by ET catheter
      contamination, whether it is macroscopic or microscopic presence of blood or
      mucus.

PMID- 19108825
TI  - Comparison of three methods for cryopreservation of human embryonic stem cells.
AB  - OBJECTIVE: To establish reliable methods for cryopreservation of human embryonic
      stem cells (hESCs). DESIGN: Prospective experimental study. SETTING: University
      laboratory. PATIENT(S): One hESC line. INTERVENTION(S): The attachment rates and
      recovery rates of cryopreserved hESCs using three different cryopreservation
      methods were compared. MAIN OUTCOME MEASURE(S): The hESCs were frozen and thawed
      by conventional cryopreservation, programmable cryopreservation, and
      vitrification method. The efficiency of cryopreservation was assessed by
      attachment rate and recovery rate. RESULT(S): The attachment rate and recovery
      rate after thawing of hESCs frozen by the conventional cryopreservation method
      were significantly lower than those of hESCs frozen by programmed
      cryopreservation and vitrification methods. Vitrification resulted in the highest
      attachment rate and recovery rate compared with the other two methods. Human ESCs
      after vitrification and programmable cryopreservation still expressed pluripotent
      markers, maintained normal karyotype, and retained their pluripotency.
      CONCLUSION(S): Our data show that programmable cryopreservation and vitrification
      methods are appropriate for cryopreservation of hESCs, whereas the conventional
      slow-rate freezing method is not appropriate for cryopreservation of hESCs.

PMID- 19108826
TI  - Tissue culture before transplantation of frozen-thawed human fetal ovarian tissue
      into immunodeficient mice.
AB  - OBJECTIVE: To evaluate the effects of tissue culture on the viability and
      development of follicles in frozen-thawed human fetal ovarian tissue before
      transplantation into severe combined immunodeficient (SCID) mice and to determine
      the optimal duration of pretransplant tissue culture. DESIGN: Experimental
      prospective study. SETTING: Animal center and reproductive laboratories in
      university hospitals. INTERVENTION(S): Frozen-thawed human fetal ovarian tissue
      samples from 20-week-old abortuses were randomly divided into four groups and
      cultured in vitro for 0, 3, 6, or 9 days before being xenografted into kidney
      capsules of bilaterally oophorectomized severe combined immunodeficient (SCID)
      mice. Grafts were removed 16 weeks after transplantation. Histological analysis
      and assessment of proliferative cell nuclear antigen (PCNA) expression levels
      were used to evaluate the survival and development of follicles. RESULT(S): The
      proportion of growing follicles was significantly increased in groups cultured
      before transplantation as compared with the noncultured group. Sixteen weeks
      after transplantation, the number of follicles in the cultured grafts was higher
      than that in the noncultured grafts. Grafts cultured for 6 or 9 days showed
      higher proportions of preantral and antral follicles than grafts cultured for 0
      or 3 days. PCNA immunohistochemical analysis indicated that follicle cells were
      in a proliferative state after culture and transplantation. CONCLUSION(S): The
      viability and development of human fetal follicles may be improved by
      pretransplant tissue culture. The optimal culture duration before transplantation
      of fetal ovarian tissue is 6 days.

PMID- 19108827
TI  - Testicular spermatozoa have statistically significantly lower DNA damage compared
      with ejaculated spermatozoa in patients with unsuccessful oral antioxidant
      treatment.
AB  - OBJECTIVE: To compare DNA damage in ejaculated and testicular spermatozoa in
      patients with previously unsuccessful oral antioxidant treatment. DESIGN:
      Prospective clinical study. SETTING: University-affiliated teaching hospital.
      PATIENT(S): Twelve men with persistently high sperm DNA damage. INTERVENTION(S):
      Evaluation of DNA damage of ejaculated and testicular spermatozoa by terminal
      deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick end labeling
      (TUNEL) assay. MAIN OUTCOME MEASURE(S): The DNA damage of ejaculated spermatozoa
      compared with that of testicular spermatozoa, both samples collected on the day
      of intracytoplasmic sperm injection. RESULT(S): Ejaculated spermatozoa showed a
      threefold higher DNA damage when compared with testicular samples (39.7% +/- 14.8
      vs. 13.3% +/- 7.3). CONCLUSION(S): Our results indicated that in patients with
      previously unsuccessful oral antioxidant treatment the retrieved testicular
      spermatozoa had a lower degree of DNA damage compared with ejaculated sperm
      collected on the same day.

PMID- 19108828
TI  - Genetic variations of solute carrier family 30 (zinc transporter) member 8
      (SLC30A8) are not associated with polycystic ovary syndrome.
AB  - No statistically significant differences in genotype and allele frequencies of
      single nucleotide polymorphism (SNP) rs13266634 in gene SLC30A8 were found
      between patients with polycystic ovary syndrome (PCOS) and healthy controls. No
      associations were observed between genotype of rs13266634 and the quantitative
      clinical features of PCOS patients in the PCOS group after adjustment for body
      mass index.

PMID- 19108829
TI  - Nuclear maturation and structural components of nonhuman primate cumulus-oocyte
      complexes during in vivo and in vitro maturation.
AB  - OBJECTIVE: To compare cumulus cell structure and timing of oocyte maturation of
      in vitro-matured (IVM) and in vivo-matured (VVM) nonhuman primate oocytes.
      DESIGN: In vivo maturation and in vitro maturation of oocytes. SETTING: Animal
      cell culture laboratory. ANIMAL(S): Forty-eight female rhesus macaques.
      INTERVENTION(S): Fifteen animals were administered FSH, and aspirated oocytes
      were cultured in vitro for 0, 3, 6, 12, or 24 hours (IVM). Thirty-three animals
      were administered FSH and hCG, and oocytes were collected 3, 6, 12, or 28-30
      hours after hCG (VVM). MAIN OUTCOME MEASURE(S): Nuclear maturation and
      microtubule scores of oocytes and actin and tubulin transzonal processes of
      cumulus cells. Embryo development was observed for VVM oocytes. RESULT(S): The
      rate of nuclear maturation was faster for IVM oocytes compared with VVM oocytes.
      Actin transzonal processes decreased 0-12 hours after hCG administration for VVM
      oocytes. Tubulin transzonal processes of IVM and VVM oocytes decreased from 0 to
      24 hours and from 0 to 3 hours, respectively. Embryo development improved as VVM
      time increased. CONCLUSION(S): Nuclear maturation and remodeling of cumulus
      oocyte complex structural components associated with in vitro maturation do not
      parallel those of oocyte maturation in vivo, indicating that in vitro culture
      conditions continue to be suboptimal.

PMID- 19108830
TI  - Asymmetric dimethylarginine levels and carotid intima-media thickness in obese
      patients with polycystic ovary syndrome and their relationship to metabolic
      parameters.
AB  - OBJECTIVE: To evaluate the plasma asymmetric dimethyl arginine (ADMA) levels and
      carotid intima-media thickness (IMT) in patients with polycystic ovary syndrome
      (PCOS). DESIGN: Prospective study. SETTING: University medical center.
      PATIENT(S): Thirty-five patients with PCOS and 31 healthy controls.
      INTERVENTION(S): Peripheral venous puncture, ultrasonography, oral glucose
      tolerance test (OGTT). MAIN OUTCOME MEASURE(S): Plasma ADMA, serum FSH, LH,
      dehydroepiandrosterone sulfate (DHEAS), free T and total T, insulin, fasting
      plasma glucose, total cholesterol, high-density lipoprotein (HDL) cholesterol,
      low-density lipoprotein (LDL) cholesterol, triglyceride, homocysteine,
      fibrinogen, C-reactive protein, and carotid IMT. RESULT(S): The PCOS group had
      higher levels of androgens, triglycerides, homocysteine, insulin, and homeostasis
      model assessment of insulin resistance when compared with controls. There were no
      significant differences in ADMA levels and IMT between the two groups. The
      fasting plasma glucose, total cholesterol, HDL cholesterol, LDL cholesterol,
      fibrinogen, and C-reactive protein levels were not different among the groups.
      Intima-media thickness was significantly correlated with DHEAS, but there was no
      association between IMT and ADMA. CONCLUSION(S): Results of our study revealed
      that ADMA levels and carotid IMT in patients with PCOS are not different from
      healthy controls.

PMID- 19108831
TI  - Bone morphogenetic protein 7 (BMP-7) increases the expression of follicle
      stimulating hormone (FSH) receptor in human granulosa cells.
AB  - OBJECTIVE: To examine the effect of bone morphogenetic protein 7 (BMP-7) on FSH
      receptor (FSHR) expression in human granulosa cells. DESIGN: Laboratory study
      using human samples. SETTING: University hospital. PATIENT(S): Human granulosa
      cells were obtained from 60 women undergoing oocyte retrieval for IVF.
      INTERVENTION(S): Human granulosa cells (GCs) were cultured with recombinant BMP
      7, followed by RNA extraction. MAIN OUTCOME MEASURE(S): mRNA levels of GCs were
      measured by real-time reverse-transcription polymerase chain reaction. RESULT(S):
      Bone morphogenetic protein 7 increased FSHR gene expression in human luteinized
      granulosa cells, whereas it decreased LH receptor gene expression. Bone
      morphogenetic protein 7 also increased FSH-induced cyclic adenosine monophosphate
      production in GCs, indicating up-regulation of the cellular response to FSH.
      Although BMP-7 increased gene expression of activin-betaA and -betaB in GCs,
      inhibition of activin function did not affect the BMP-7-induced FSHR gene
      expression. CONCLUSION(S): These findings provide new insight into the biologic
      function of BMP-7 in the human ovary and demonstrate its unique mechanism of
      regulating FSHR action.

PMID- 19108832
TI  - Network analyses of differentially expressed proteins in amniotic fluid
      supernatant associated with abnormal human karyotypes.
AB  - OBJECTIVE: To investigate the functional roles of differentially expressed
      proteins in the amniotic fluid supernatant (AFS) with abnormal karyotypes.
      DESIGN: Basic and clinical research. SETTING: University hospital. PATIENT(S):
      Samples of AFS from 34 fetuses with normal-karyotype, 17 with trisomy 18, and 19
      with trisomy 21. INTERVENTION(S): Two-dimensional chromatography followed by mass
      spectrometry to identify the proteins differentially expressed in AFS of trisomy
      18 or trisomy-21 fetuses. MAIN OUTCOME MEASURE(S): Differentially expressed
      proteins were confirmed with Western blot analysis and ELISA. The roles of
      biologic networks in the pathophysiology of aneuploidies were analyzed using
      MetaCore mapping tools. RESULT(S): Levels of apolipoprotein A1, AP-3mu, and
      antitrypsin were significantly decreased in trisomy-18 AFS, whereas placental
      protein-14 was increased. On the other hand, apolipoprotein A1 was decreased in
      trisomy-21 AFS, but antitrypsin, prealbumin, and transferrin were increased in
      trisomy 21. Biologic network analyses revealed that the proteins of the trisomy
      18 AFS network were involved in immune processes, dysfunction of skin
      pigmentation, and platelet disorders, whereas those of trisomy 21 were associated
      with dysfunctional lipid and cholesterol metabolism, processes of metal ion
      transport, adenosine triphosphate metabolism, and energy-coupled protein
      transport. CONCLUSION(S): The combined use of quantitative proteomics and
      functional network analyses may integrally analyze the pathophysiology of
      abnormal karyotypes.

PMID- 19108833
TI  - Resveratrol inhibits the mTOR mitogenic signaling evoked by oxidized LDL in
      smooth muscle cells.
AB  - OBJECTIVES: Smooth muscle cell (SMC) proliferation is a major feature in
      atherosclerosis, since it contributes to the formation of the fibrous cap, thus
      to plaque stability, but also to arterial stenosis and post-angioplasty
      restenosis. Among the various mitogenic signaling pathways involved in SMC
      proliferation, the mTOR pathway regulates both the cell cycle and cell growth.
      Resveratrol, a polyphenolic compound from grapes and red wine, has potential anti
      atherogenic and anti-cancer properties. This work was designed to investigate the
      activation of the mTOR pathway by the proatherogenic oxidized LDL (oxLDL) in SMC,
      and the potential inhibitory effect of resveratrol. RESULTS: mTOR and its
      downstream target p70S6 kinase are phosphorylated and activated by mitogenic
      concentrations of oxLDL (50 microg/ml), and are involved in SMC proliferation, as
      assessed by the inhibitory effect of the mTOR inhibitor rapamycin. The activation
      of mTOR signaling by oxLDL, requires the upstream activation of PI3K and Akt, as
      assessed by the inhibitory effect of the PI3K inhibitor Ly294002 on mTOR
      activation and DNA synthesis. Resveratrol blocked the oxLDL-induced
      phosphorylation and activation of the PI3K/Akt/mTOR/p70S6K pathway and strongly
      inhibited both the DNA synthesis and proliferation of SMC. This activity is
      independent of the anti-oxidant effect and of AMPK activation by resveratrol.
      CONCLUSION: These data indicate that the mTOR pathway is activated by oxLDL via
      PI3K/PDK1/Akt, and is required for SMC proliferation. Resveratrol blocks
      specifically this pathway, thereby inhibiting oxLDL-induced SMC proliferation.
      These data highlight a new property for resveratrol that could contribute to the
      general anti-atherogenic properties of this polyphenol.

PMID- 19108834
TI  - Cilostazol inhibits modified low-density lipoprotein uptake and foam cell
      formation in mouse peritoneal macrophages.
AB  - Internalization of modified low-density lipoprotein (LDL) via macrophage
      scavenger receptors (e.g. scavenger receptor A and CD36) is thought to play a
      crucial role in the development of atherosclerotic lesions. Cilostazol, an
      antiplatelet agent with selective phosphodiesterase 3 inhibitory action, has been
      reported to ameliorate atherosclerosis in mouse models. However, the effect of
      cilostazol on modified LDL uptake in macrophages is not known. Thus, we
      investigated the effect of cilostazol on LDL uptake in mouse peritoneal
      macrophages (MPM). Cilostazol significantly inhibited oxidized and acetylated LDL
      uptake in MPM, while cyclic AMP (cAMP)-elevating agents, db-cAMP and other
      phosphodiesterase 3 or 4 inhibitors, did not inhibit the uptake. Cilostazol did
      not change cytosolic cAMP levels in MPM, and a protein kinase A (PKA) inhibitor
      did not influence the inhibitory effects of cilostazol. Cilostazol decreased
      scavenger receptor A but not CD36 expression. Moreover, cilostazol significantly
      inhibited foam cell formation, which was represented by an increase in esterified
      cholesterol content. In conclusion, cilostazol significantly inhibits the uptake
      of modified LDL and foam cell formation in mouse peritoneal macrophages, and the
      inhibitory effect of cilostazol can be induced in a cAMP- and PKA-independent
      manner.

PMID- 19108835
TI  - Binge drinking and the progression of atherosclerosis in middle-aged men: an 11
      year follow-up.
AB  - OBJECTIVE: There is limited knowledge on drinking patterns and the progression of
      atherosclerosis. Previous studies have shown conflicting results between alcohol
      consumption and atherosclerotic progression. We investigated the association
      between the pattern of binge drinking and the 11-year progression of carotid
      atherosclerosis in a population-based sample of middle-aged men. METHODS AND
      RESULTS: This study is a part of the FinDrink Study, based on the Kuopio Ischemic
      Heart Disease Risk Factor Study. We investigated the effect of drinking patterns
      on the changes in maximum and mean intima-media thickness, including changes in
      maximum plaque height in 751 participants as measured by carotid ultrasound. The
      increased atherosclerosis progression was statistically significant among those
      men with binge drinking of >or=6 drinks per session (22.4% of total number of
      participants) using different covariates in different models according to the
      mean increase in maximum intima-media thickness (Model 1, p=0.008; Model 2,
      p=0.031, Model 3, p=0.037) and the mean increase in maximum plaque height (Model
      1, p=0.002; Model 2, p=0.012, Model 3, p=0.017). CONCLUSION: Our study shows that
      binge drinking was associated with an increased atherosclerosis progression
      during an 11-year follow-up in middle-aged men, independent of the total alcohol
      consumption.

PMID- 19108836
TI  - Effects of trunk deformation on trunk center of mass mechanical energy estimates
      in the moving horse, Equus caballus.
AB  - The estimation of the position of the center of mass (CM) is essential in a wide
      range of biomechanical analyses. In horses, the majority of the body mass is
      contained in the trunk and in most studies, the trunk is assumed to be rigid.
      However, this rigidity assumption has not been tested. We quantified changes in
      the position of the trunk CM due to external shape changes by measuring the
      kinematics of a mesh encompassing the trunk. Using a frame of reference fixed to
      the horse's spine, we described the shape deformation of the trunk during
      walking. In addition, we tested for speed and individual differences. The
      significance of any trunk deformation was illustrated by calculating mechanical
      energy profiles. Errors in the estimation of the trunk CM due to a rigid body
      approach were always small in the vertical direction, but can be significant in
      the transverse direction and in the longitudinal direction at high walking
      speeds. This is enough to change the mechanical energy expenditure estimates up
      to 25%. When extrapolating the position of the trunk CM from cadaver data, one
      should be aware of this extra source of error, separated from the measurement
      error of the cadaver CM. We also found considerable inter-individual variation,
      which complicates theoretical correction routines. We suggest using extra markers
      on the trunk during gait analysis to correct this CM shift experimentally.

PMID- 19108838
TI  - Utilization of solid-phase microextraction-high-performance liquid chromatography
      in the determination of aromatic analyte partitioning to imidazolium-based ionic
      liquid micelles.
AB  - A solid-phase microextraction (SPME)-high-performance liquid chromatography
      (HPLC) approach is used, for the first time, to study the partitioning behavior
      of eight aromatic analytes to three imidazolium-based ionic liquid micelles,
      namely, 1-hexadecyl-3-methylimidazolium bromide (HDMIm-Br), 1-hexadecyl-3
      butylimidazolium bromide (HDBIm-Br), and 1,3-didodecylimidazolium bromide (DDDDIm
      Br). The model used to calculate the partition coefficients is improved by
      determining the accurate critical micelle concentration (CMC) value of the
      studied IL-micelles, which considers the nature and amount of organic modifier
      used in the experiments. Proper CMC values in the model improve the quality of
      the results and decrease the differences between theoretical and experimental
      intercepts. Surface tensiometry has been utilized to determine the CMC values for
      the micelles at different acetonitrile contents (1% and 1.5%, v/v). The
      calculated partition coefficient values for polycyclic aromatic hydrocarbons
      (PAHs) oscillate between 631 and 5980, whereas aromatic analytes with a lower
      number of fused rings in their structures suffer non-partitioning to any of the
      IL-micelles. The obtained partition coefficients to IL-micelles were highest with
      the DDDDIm-Br IL and were always higher than those obtained with the traditional
      surfactant cetyltrimethyl ammonium bromide (CTAB).

PMID- 19108837
TI  - Sulfated and sulfonated polysaccharide as chiral stationary phases for capillary
      electrochromatography and capillary electrochromatography-mass spectrometry.
AB  - The applications of polysaccharide phenyl carbamate derivatives as chiral
      stationary phases (CSPs) for capillary electrochromatography (CEC) are often
      hindered by longer retention times, especially using a normal-phase (NP) eluent
      due to very low electroosmotic flow (EOF). Therefore, in this study, we propose
      an approach for the aforementioned problems by introducing two new types of
      negatively charged sulfate and sulfonated groups for polysaccharide CSPs. These
      CSPs were utilized to pack CEC columns for enantioseparation with a NP eluent.
      Compared to conventional cellulose tris(3,5-dimethylphenyl carbamate) or CDMPC
      CSPs, the sulfated CDMPC CSP (sulfur content 4.25%, w/w) shortened the analysis
      time up to 50% but with a significant loss of enantiomeric resolution
      (approximately 60%). On the other hand, the sulfonated CDMPC CSP (sulfur content
      1.76%, w/w) not only provided fast throughput but also maintained excellent
      resolving power. In addition, its synthesis is much more straightforward than the
      sulfated one. Furthermore, we studied several stationary phase parameters (CSP
      loading and silica gel pore size) and mobile phase parameters (including type of
      mobile phase and its composition) to evaluate the throughput and
      enantioselectivity. Using the optimized conditions, a chiral pool containing 66
      analytes was screened to evaluate the enantioselectivity under three different
      mobile phase modes (i.e., NP, polar organic phase (POP) and reversed-phase (RP)
      eluents). Among these mobile phase modes, the RP mode showed the highest success
      rate, whereas some degree of complementary enantioselectivity was observed with
      NP and POP. Finally, the feasibility of applying this CSP for CEC-MS
      enantioseparation using internal tapered column was evaluated with NP, POP and RP
      eluents. In particular, the NP-CEC-MS provided significantly enhanced sensitivity
      when methanol was replaced with isopropanol in the sheath liquid. Using
      aminoglutethimide as model chiral analyte, all three modes of CEC-MS demonstrated
      excellent durability as well as excellent reproducibility of retention time and
      enantioselectivity.

PMID- 19108839
TI  - Intermittent counter-current extraction as an alternative approach to
      purification of Chinese herbal medicine.
AB  - This paper describes intermittent counter-current extraction, a novel method of
      using a conventional twin column counter-current chromatograph to either split a
      sample into two groups of compounds or extract and enrich a target compound from
      a crude extract. The first method is demonstrated by splitting a model mixture of
      four compounds into two groups. The second method is demonstrated by the
      extraction and enrichment of a high value target compound, triptolide, from a
      Chinese herbal medicine crude extract of Tripterygium wilfordii Hook. f., where
      it is found at low concentration (2%). This was achieved by retaining and
      enriching the target compound within the column while washing away all other
      components of the crude material. The success of the first method allowed the
      second method to be carried out without the need for costly preliminary
      experiments with the high value sample. 188mg of triptolide at greater than 98%
      purity was separated from 9.2g of crude extract, using 10l of solvent in a 3-h
      separation.

PMID- 19108840
TI  - A simple and fast liquid-liquid extraction method for the determination of
      2,2',4,4',5,5'-hexachlorobiphenyl (CB-153) and 1,1-dichloro-2,2-bis(p
      chlorophenyl)-ethylene (p,p'-DDE) from human serum for epidemiological studies on
      type 2 diabetes.
AB  - A simple and fast method is presented to be used for example in studies on the
      relationship between serum levels of persistent organic pollutants and type 2
      diabetes mellitus. Method is based on liquid-liquid extraction and gas
      chromatography coupled with high-resolution mass spectrometry. In the sample pre
      treatment special attention was paid to minimize the number of sample
      manipulation steps and the amounts of organic solvents needed. Compounds analyzed
      were 2,2',4,4',5,5'-hexachlorobiphenyl (PCB-153) and 1,1-dichloro-2,2-bis (p
      chlorophenyl)-ethylene (p,p'-DDE), the major metabolite of DDT. The method
      included extraction and cleanup of 0.2ml of serum in a single test tube and
      subsequent analysis of the extract from 0.2ml final volume. Validation was
      conducted to explore the performance of the method. The limits of detection for
      p,p'-DDE and PCB-153 based on the standard deviation of the blank samples were
      4.3 and 3.1pg/ml, respectively. Repeatability was less than 2.5% at three
      concentration levels tested and recovery from Certified Reference Material SRM
      1589a was 84% for p,p'-DDE and 87% for PCB-153 of the certified values,
      respectively. Serum samples from the AMAP intercalibration round 2008-2 were also
      analyzed, and results were 101-116% of the assigned values. The presented method
      was used for an epidemiological study with more than 700 serum samples from a
      type 2 diabetes cohort from Sweden.

PMID- 19108841
TI  - Simultaneous conduction of two- and three-phase hollow-fiber-based liquid-phase
      microextraction for the determination of aromatic amines in environmental water
      samples.
AB  - This paper describes a simultaneously performed two-/three-phase hollow-fiber
      based liquid-phase microextraction (HF-LPME) method for the determination of
      aromatic amines with a wide range of pK(a) (-4.25 to 4.6) and logK(OW) (0.9-2.8)
      values in environmental water samples. Analytes including aniline, 4
      nitroaniline, 2,4-dinitroaniline and dicloran were extracted from basic aqueous
      samples (donor phase, DP) into the microliter volume of organic membrane phase
      impregnated into the pores of the polypropylene hollow fiber wall, then back
      extracted into the acidified aqueous solution (acceptor phase, AP) filling in the
      lumen of the hollow fiber. The mass transfer of the analytes from the donor phase
      through the organic membrane phase into acceptor phase was driven by both the
      counter-coupled transport of hydrogen ions and the pH gradient. Afterwards, the
      hollow fiber was eluted with 50 microL methanol to capture the analytes from both
      the organic membrane and the acceptor phase. Factors relevant to the enrichment
      factors (EFs) were investigated. Under the optimized condition (DP: 100 mL of 0.1
      M NaOH with 2 M Na(2)SO(4); organic phase: di-n-hexyl with 8% trioctylphosphine
      oxide (TOPO); AP: 10 microL of 8 M HCl; extraction time of 80 min), the obtained
      EFs were 405-2000, dynamic linear ranges were 5-200 microg/L (R>0.9976), and
      limits of detection were 0.5-1.5 microg/L. The presence of humic acid (0-25 mg/L
      dissolved organic carbon) had no significant effect on the extraction efficiency.
      The proposed procedure worked very well for real environmental water samples with
      microgram per liter level of analytes, and good spike recoveries (80-103%) were
      obtained.

PMID- 19108842
TI  - Role of counter-current chromatography in the modernisation of Chinese herbal
      medicines.
AB  - This review focuses on the growing popularity of using counter-current
      chromatography (CCC), with its liquid stationary phase, as one of the prime
      methods for isolating compounds from Chinese herbal medicines (CHMs). 198
      publications are reviewed covering 108 different plant species from 56 plant
      families. These describe the isolation of 354 different molecules across a wide
      range of polarities, chemical classes and molecular weights (in the range 100
      1000 Da). The suitability of CCC for the separation of active compounds from CHM,
      the phase systems used, how CCC has developed in China, compounds isolated, CCC
      instrumentation, performance, operational issues and innovations, all supported
      by detailed cross-referencing, are described. It is concluded that CCC is making
      an increasingly important contribution to the modernisation of Chinese herbal
      medicines.

PMID- 19108843
TI  - Purification of high-throughput organic synthesis libraries by counter-current
      chromatography.
AB  - Experiments were performed to evaluate whether counter-current chromatography
      (CCC) could function as an alternative purification method to reversed-phase high
      performance liquid chromatography (RP-HPLC) and normal-phase supercritical fluid
      chromatography (SFC). RP-HPLC and SFC are the routine methods currently used in
      our high-throughput purification (HTP) facility for the purification of high
      throughput organic synthesis (HTOS) libraries and medicinal chemistry reaction
      mixtures. Pre-equilibration of the solvent mixture layers was not mandatory for
      effective chromatography when hexanes-ethyl acetate-methanol-water (HEMW) solvent
      mixtures were used. Key to the use of CCC for high-throughput applications is the
      ability to effectively select a solvent system appropriate to each library
      member. Pilot-scale CCC elution time was used to estimate a starting solvent
      ratio and RP-HPLC retention time was then used to adjust solvent ratios within a
      particular library. It was also found that dimethyl sulfoxide (DMSO) and DMSO
      methanol were suitable as sample injection solvents when using the HEMW solvent
      systems.

PMID- 19108844
TI  - Preparation of a mixed-mode hydrophilic interaction/anion-exchange polymeric
      monolithic stationary phase for capillary liquid chromatography of polar
      analytes.
AB  - A novel cationic hydrophilic interaction monolithic stationary phase based on the
      copolymerization of 2-(methacryloyloxy)ethyltrimethylammonium methyl sulfate
      (META) and pentaerythritol triacrylate (PETA) in a binary porogenic solvent
      consisting of cyclohexanol/ethylene glycol was designed for performing capillary
      liquid chromatography. While META functioned as both the ion-exchange sites and
      polar ligand provider, the PETA, a trivinyl monomer, was introduced as cross
      linker. The monolithic stationary phases with different properties were easily
      prepared by adjusting the amount of META in the polymerization solution as well
      as the composition of the porogenic solvent. The hydrophilicity of the monolith
      increased with increasing content of META in the polymerization mixture. A
      typical hydrophilic interaction chromatography mechanism was observed when the
      content of acetonitrile in the mobile phase was higher than 20%. The poly(META-co
      PETA) monolith showed very good selectivity for neutral, basic and acidic polar
      analytes. For polar-charged analytes, both hydrophilic interaction and
      electrostatic interaction contributed to their retention. Peak tailing of basic
      compounds was avoided and the efficient separation of benzoic acid derivatives
      was obtained.

PMID- 19108845
TI  - Editorial on "Role of counter-current chromatography in the modernization of
      Chinese herbal medicines" by I.A. Sutherland and D. Fisher.

PMID- 19108846
TI  - Analysis of quinocide in unprocessed primaquine diphosphate and primaquine
      diphosphate tablets using gas chromatography-mass spectrometry with supersonic
      molecular beams.
AB  - Malaria is one of the most widespread and deadly diseases on the planet. Every
      year, about 500 million new cases are diagnosed, and the annual death toll is
      about 3 million. Primaquine has strong antiparasitic effects against gametocytes
      and can therefore prevent the spread of the parasite from treated patients to
      mosquitoes. It is also used in radical cures and prevents relapse. Consequently,
      primaquine is an often-used drug. In this study the separation of unprocessed
      primaquine from the contaminant quinocide based on gas chromatography-mass
      spectrometry with supersonic molecular beam (SMB) is presented and 7.5 mg
      primaquine diphosphate tablets were analyzed. We present a novel method for fast
      determination of quinocide which is an isomer of primaquine as the main
      contaminant in unprocessed primaquine and in its medical form as tablets by gas
      chromatography-mass spectrometry with SMB (also named supersonic GC-MS).
      Supersonic GC-MS provides enhanced molecular ion without any ion source related
      peak tailing plus extended range of compounds amenable for GC-MS analysis. In
      addition, major isomer mass spectral effects were revealed in the mass spectra of
      primaquine and quinocide which facilitated the unambiguous identification of
      quinocide in primaquine tablets. Fast GC-MS analysis is demonstrated with less
      then 2 min elution time of the drug and its main contaminants.

PMID- 19108847
TI  - Electrostatic deposition of polycations and polyanions onto cysteine monolayers.
AB  - Electrochemical impedance spectroscopy and the quartz crystal microbalance are
      used to monitor the deposition of polyelectrolytes onto an interface modified
      with a monolayer of cysteine. When using an anionic redox probe, Fe(CN)(6)(-4),
      the impedance of the cysteine modified electrode is a function of the solution
      pH; the charge-transfer resistance being higher at basic pH, and smaller under
      acidic conditions relative to the value found when the solution is buffered near
      the pI for cysteine. This behavior is consistent with the electrostatic
      interaction between the anionic redox probe and the net charge of the interface.
      After exposure of the cysteine-modified interface to 0.10 mol L(-1) HCl solutions
      containing polystyrene sulfonate, the impedance of the modified interface
      increases. This behavior is consistent with the interface having a net negative
      charge, and suggests that the polyanion is confined to the interface. Quartz
      crystal microbalance measurements also show that 700+/-20 ng of the PSS is
      deposited under the acidic conditions. After exposure to 0.10 mol L(-1) NaOH
      solutions containing poly(diallyldimethyl)ammonium chloride, the impedance of the
      modified interface decreases, consistent with the electrostatic assembly of the
      polycation to the cysteine monolayer under these conditions. Quartz crystal
      microbalance measurements indicate that 770+/-40 ng of the
      poly(diallyldimethylammonium chloride) are deposited under the basic conditions.

PMID- 19108848
TI  - Polyelectrolyte-linked film assemblies of nanoparticles and nanoshells: growth,
      stability, and optical properties.
AB  - Multi-layer films of nanoparticles and nanoshells featuring various polymeric
      linkage molecules have been assembled and their optical properties characterized.
      The growth dynamics, including molecular weight effects, and stability of the
      various nanoparticle film constructions, using both single polymer as well as
      combinations of alternating charge polyelectrolytes as linking mechanisms, are
      presented. The polymeric linkers studied include poly-L-lysine, poly-L-arginine,
      poly(allylamine hydrochloride), and polyamidoamine dendrimers. Significantly air
      stable films were achieved with the use of multi-layered polymeric bridges
      between the nanoparticles and nanoshells. Optical sensitivity normally observed
      with these nanomaterials in solution was observed for their corresponding film
      geometries, with the nanoshell films exhibiting a markedly higher ability to
      report their local dielectric environment.

PMID- 19108849
TI  - Instability analysis of torsional MEMS/NEMS actuators under capillary force.
AB  - The static and dynamic instabilities of a torsional MEMS/NEMS actuator caused by
      capillary effects are studied, respectively. An instability number, eta, is
      defined, and the critical gap distance, g(cr), between the mainplate and the
      substrate is derived. According to the values of eta and g, the instability
      criteria of the actuator are presented. The dimensionless motion equation of the
      MEMS/NEMS torsional actuator is derived when it makes nonlinear oscillation under
      capillary force. The qualitative analysis of the nonlinear equation is made, and
      the phase portraits are presented on the phase plane. In addition, the
      bifurcation phenomena in the system are also analyzed.

PMID- 19108850
TI  - Comparative evaluation of diagnostic methods for Lawsonia intracellularis
      infection in pigs, with emphasis on cases lacking characteristic lesions.
AB  - In this study the following methods for the diagnosis of Lawsonia intracellularis
      infection in pigs were compared in relation to a reference method (examination of
      ileal mucosal scrapings by the polymerase chain reaction [PCR]): Warthin-Starry
      (WS) staining of tissue sections, immunohistochemistry (IHC), in-situ
      hybridization (ISH), and PCR examination of faeces and of paraffin wax-embedded
      samples of ileum. Of 204 pigs examined, 32 were considered on the basis of the
      PCR to be infected. Gross and histopathological examination, including the use of
      WS staining, were of limited value. PCR examination of faeces proved to be the
      most sensitive (sensitivity 70%) of the methods used but, due to the occurrence
      of false positives, its specificity (95%) was the lowest. IHC (sensitivity 66%,
      specificity 99%) and ISH (sensitivity 54%, specificity 100%) were clearly
      superior to examination of WS-stained sections (sensitivity 34%, specificity
      100%) for routine diagnosis; although less sensitive than the PCR, they indicated
      only cases of clinical relevance and, moreover, were capable of distinguishing
      different stages and levels of infection. Because examination of paraffin wax
      embedded tissue by the PCR was shown to be associated with low sensitivity (41%),
      IHC was regarded as the method of choice for retrospective studies.

PMID- 19108851
TI  - Hemimedullary infarct with ipsilateral hemiplegia: a vertebral artery dissection
      syndrome?
AB  - BACKGROUND: Hemimedullary syndrome is very rare and combines the clinical
      features of lateral and medial medullary infarctions. In patients with
      hemimedullary syndrome, the presence of ipsilateral, rather than contralateral
      hemiplegia, is rare. OBJECTIVE: To describe a patient with an infarction in the
      right hemimedulla with an ipsilateral motor deficit due to dissection of the
      right vertebral artery (VA) and to assess whether the ipsilateral hemiplegia may
      be the result of a specific stroke mechanism. METHODS: We reviewed the reports of
      hemimedullary syndrome in the literature and compared the characteristics of
      patients with dissection of the VA with those with VA atherosclerotic disease.
      RESULTS: In our patient, magnetic resonance angiography showed dissection of the
      right VA to be the cause of the stroke. In a review of the literature (including
      our case), hemiplegia was ipsilateral to the infarction in four of the five
      patients with VA dissection, but contralateral in all six patients with
      atherosclerotic disease of the VA (p=0.01). In all five cases of VA dissection,
      the right hemimedulla was involved, while, in the six cases of atherosclerotic
      disease, the left side of the medulla oblongata was affected in five instances
      and the right side in one (p=0.01). CONCLUSION: Dissection of the VA may provoke
      a hemimedullary lesion at a lower level than atherosclerosis, thus affecting
      medullary-penetrating branches that irrigate the medulla immediately below the
      pyramidal decussation. Hemimedullary syndrome accompanied by ipsilateral motor
      deficit should raise suspicion of dissection of the VA.

PMID- 19108852
TI  - Progression of acute cochleovestibulopathy into anterior inferior cerebellar
      artery infarction.
AB  - Antemortem diagnosis of isolated inner ear infarction remains a diagnostic
      challenge since current imaging techniques do not permit differentiation of
      isolated labyrinthine infarction from other more benign disorders involving the
      inner ear. An 81-year-old woman with diabetes, hypertension and
      hypercholesterolemia presented with vertigo and hearing loss. Initial examination
      revealed findings of left cochleovestibular labyrinthitis without brainstem or
      cerebellar signs. MRIs including the diffusion-weighted images were normal. Five
      days later, however, she developed dysarthria, and decreased facial sensation,
      subtle facial palsy, and dysmetria in the left side. Follow-up MRI was consistent
      with acute infarctions in the territory of anterior inferior cerebellar artery
      (AICA), involving the left lateral pons, left middle cerebellar peduncle, and
      inferolateral cerebellum. AICA infarction should be considered in acute
      audiovestibular syndrome, especially in aged patients with vascular risk factors,
      even though the classic brainstem or cerebellar signs are absent.

PMID- 19108853
TI  - Intra-coastal ballast water flux and the potential for secondary spread of non
      native species on the US West Coast.
AB  - Ballast water is a dominant mechanism for the interoceanic and transoceanic
      dispersal of aquatic non-native species (ANS), but few studies have addressed ANS
      transfers via smaller scale vessel movements. We analyzed ballast water reporting
      records and ANS occurrence data from four US West Coast port systems to examine
      patterns of intra-coastal ballast water transfer, and assess how ballast
      transfers may have influenced the secondary spread of ANS. In 2005, one third of
      the vessels arriving to the US West Coast originated at one of four West Coast
      port systems (intra-coastal traffic). These vessels transported and discharged
      27% (5,987,588 MT) of the total ballast water volume discharged at these ports
      that year. The overlap of ANS (shared species) among port systems varied between
      3% and 80%, with the largest overlap occurring between San Francisco Bay and
      LA/Long Beach. Our results suggest that intra-coastal ballast water needs further
      consideration as an invasion pathway, especially as efforts to promote short-sea
      shipping are being developed.

PMID- 19108854
TI  - Dibenzocyclooctadiene lignans from Kadsura philippinensis.
AB  - Lignans with the dibenzocyclooctadiene skeleton, kadsuphilols I-L, and one C(19)
      homolignan, kadsuphilol M, were isolated by chromatographic fractionation of an
      ethyl acetate extract of the aerial parts of Kadsura philippinensis. Their
      structures were elucidated through extensive spectroscopic methods, including
      HRESIMS and 2D NMR experiments (HMQC, COSY and HMBC). The stereochemistry at the
      chiral centers and the biphenyl moist, were determined using NOESY, as well as
      analysis of CD spectra, respectively. The relative configuration of heteroclitin
      J was confirmed by single crystal X-ray crystallographic analysis. The in vitro
      radical-scavenging activities of these compounds by using DPPH were evaluated.

PMID- 19108855
TI  - Tissue expression of ketohexokinase in cats.
AB  - Ketohexokinase (KHK) metabolizes dietary fructose and is an important regulator
      of hepatic glucose metabolism. The veterinary literature contains conflicting
      data regarding the role of KHK in feline fructose metabolism. The study
      objectives were to determine tissue expression of KHK mRNA and protein in cats,
      with special emphasis on hepatic expression. KHK mRNA and protein expression were
      determined using routine RT-PCR and immunoblot techniques. KHK mRNA was detected
      in feline liver, pancreas, spleen and striated muscle but not in lung. The
      partial sequence of feline KHK mRNA obtained was highly similar to known KHK mRNA
      sequences. Immunoblot studies confirmed KHK protein expression in the feline
      liver. The tissue distribution of KHK mRNA in cats is similar to KHK expression
      in other species. KHK mRNA and protein expression in feline liver is consistent
      with previous reports of hepatic fructokinase activity in this species.

PMID- 19108856
TI  - [Salivary stones and stenosis. A comprehensive classification].
AB  - INTRODUCTION: Sialendoscopy and sialo-MRI enable diagnosis of salivary gland
      obstructive pathologies, such as lithiasis, stenosis and dilatations. Therefore,
      a classification of these pathologies is needed, allowing large series
      comparisons, for better diagnosis and treatment of salivary pathologies. MATERIAL
      AND METHODS: With help from people from the European Sialendoscopy Training
      Center (ESTC), the results of sialographies, sialoMRI and sialendoscopies, a
      comprehensive classification of obstructive salivary pathologies is described,
      based on the absence or presence of lithiasis (L), stenosis (S) and dilatation
      (D) ("LSD" classification). DISCUSSION: It appears that a classification of
      salivary gland obstructive pathologies should be described. We hope it will be
      widely used and of course criticized to be improved and to compare the results of
      salivary gland diagnostic methods, such as sialography and sialendoscopy and also
      the results and indications for salivary gland therapeutic methods, such as
      lithotripsy, sialendoscopy and/or open surgery.

PMID- 19108857
TI  - [Cerebromediastinal tuberculosis in a child with a probable Say-Barber-Miller
      syndrome: a causative link?].
AB  - INTRODUCTION: Tuberculosis continues to be a public health problem in emerging
      countries with a recent evidence of increased incidence of extrapulmonary
      localization in developed countries probably linked to HIV. To our knowledge the
      occurrence of cerebro-mediastinal tuberculosis in an immuno-competent child has
      not been previously described; moreover the child we describe has a probable Say
      Barber-Miller syndrome. We discuss a putative causative link between this
      syndrome and the occurrence of tuberculosis. CASE REPORT: A seven-year-old girl
      presented to our department with a history of infantile encephalopathy since
      birth characterized by a facial dysmorphy (evocative of a bird face),
      microcephaly, and mental retardation, and with recurrent infections. The child
      had complained of back pain for several months; the parents reported anorexia,
      loss of weight. Spinal and cerebral MRI showed a mediastinal mass involving the
      spine and cerebral lesions evocative of tuberculomas. The tuberculin interdermal
      reaction was positive. Culture of a vertebral biopsy was positive for Koch
      bacillus. Anti-tuberculosis treatment improved general and local status. An
      extensive immunological work-up was normal. CONCLUSION: [corrected] This
      observation is exceptional in many aspects: very early age of onset of
      extrapulmonary tuberculosis, no immune deficit, association with a rare
      congenital neurological syndrome. We discuss the possible link between this
      entity and the occurrence of tuberculosis.

PMID- 19108858
TI  - Semi-analytical finite element analysis of elastic waveguides subjected to axial
      loads.
AB  - Predicting the influence of axial loads on the wave propagation in structures
      such as rails requires numerical analysis. Conventional three-dimensional finite
      element analysis has previously been applied to this problem. The process is
      tedious as it requires that a number of different length models be solved and
      that the user identify the computed modes of propagation. In this paper, the more
      specialised semi-analytical finite element method is extended to account for the
      effect of axial load. The semi-analytical finite element method includes the wave
      propagation as a complex exponential in the element formulation and therefore
      only a two-dimensional mesh of the cross-section of the waveguide is required. It
      was found that the stiffness matrix required to describe the effect of axial load
      is proportional to the mass matrix, which makes the extension to existing
      software trivial. The method was verified by application to an aluminium rod,
      where after phase and group velocities of propagating waves in a rail were
      computed to demonstrate the method.

PMID- 19108859
TI  - The rinderpest virus non-structural C protein blocks the induction of type 1
      interferon.
AB  - The innate immune response, in particular the production of type 1 interferons,
      is an essential part of the mammalian host response to viral infection. We have
      previously shown that rinderpest virus, a morbillivirus closely related to the
      human pathogen measles virus, blocks the actions of type 1 and type 2
      interferons. We show here that this virus can also block the induction of type 1
      interferon. The viral non-structural C protein appears to be the active agent,
      since expressing this protein in cells makes them resistant to activation of the
      interferon-beta promoter while recombinant virus that does not express the C
      protein activates this promoter much more than virus expressing the C protein. In
      addition, differences in activation of the interferon-beta promoter by different
      strains of rinderpest virus are reflected in differing abilities of their
      respective C proteins to block activation of the promoter by dsRNA. The C protein
      blocks the activation of this promoter induced by either cytoplasmic dsRNA or by
      Newcastle disease virus (NDV) infection, as well as activation induced by
      overexpression of several elements of the signalling pathway, including mda-5,
      RIG-I and IRF-3. The RPV C protein also blocks transcription from promoters
      responsive individually to the three transcription factors that make up the
      interferon-beta promoter enhanceosome, although it does not appear to block the
      activation of IRF-3.

PMID- 19108860
TI  - Friend murine leukemia virus A8 regulates Env protein expression through an
      intron sequence.
AB  - Friend murine leukemia virus (Fr-MLV) produces unspliced mRNAs, as well as singly
      spliced mRNAs by which the Env protein is generated. We investigated the role of
      the intron within the Fr-MLV gene in Env expression using vectors with serially
      truncated introns. The up-regulatory regions, the 361-878 and the 5135-5399
      fragments, and the down-regulatory regions, the 1904-2849 and the 3995-4287
      fragments, were found to influence the splicing efficiency. The Env protein
      expression level was proportional to the amount of env-mRNA. Furthermore, we
      found that the splicing process is important to acquire env-mRNA stability, and
      it also promotes translation of the Env protein. These splicing-dependent
      phenomena were not observed when luciferase expression vectors were analyzed.
      These findings indicated that the Env protein expression level in MLV is
      regulated at multiple steps: the env-mRNA expression level is determined by the
      splicing efficiency, and the stability of env-mRNA is acquired through the
      splicing process.

PMID- 19108861
TI  - Prevalence of norovirus and factors influencing virus concentrations during one
      year in a full-scale wastewater treatment plant.
AB  - Norovirus (NoV) is a leading cause of acute gastroenteritis and is often spread
      via wastewater contamination. Little is known about how the wastewater treatment
      process affects norovirus, and which factors influence virus concentrations. To
      investigate this, we collected wastewater samples monthly during one year at
      eight different key sites at the municipal wastewater treatment plant in
      Gothenburg, Sweden. Virus particles were concentrated using ultracentrifugation,
      viral RNA was subsequently extracted, and transformed into cDNA by reverse
      transcription. The quantification was performed with real-time PCR assays for NoV
      genogroups I (GGI) and II (GGII), respectively. We found seasonal changes of NoV
      genogroups, with the highest concentration of NoV GGII during the winter months,
      and the highest concentration of NoV GGI during the summer months. Virus
      transmission in wastewater was more stable for NoV GGI, with NoV GGII
      demonstrating larger seasonal peaks. Virus reduction took place at similar rates
      in the primary settling, and in the activated sludge in combination with the
      secondary settling. Different physicochemical parameters and incoming virus
      concentrations were correlated to reduction of NoV between different treatment
      sites. This study gives new information about NoV transmission and virus
      reduction in a wastewater treatment plant.

PMID- 19108862
TI  - Rapid extraction of sediment contaminants by pressure cycles.
AB  - Sediment contamination is a significant issue. Assessment, management, and
      monitoring of contaminated sediment require routine analyses of a large volume of
      sediment samples, which require significant preparation time including extraction
      of contaminants from samples prior to analysis. This work tested a new method of
      extracting contaminants from sediment based on the use of rapid, successive
      pressurization cycles, which involve compression of a gas into the extractive
      solvent in contact with the sediment immediately followed by decompression via
      venting. The technique improved extraction amounts and shortened preparation
      time. Tested were PCB and PAH contaminated sediment samples from various
      locations of the US, including the Passaic River, St. Louis River, Waukegan
      Harbor, and Wells National Estuarine Research Reserve. The results were compared
      to those of Soxhlet extraction. Specifically, the extraction of 15 g of sediment
      with 50 mL of hexane-acetone (1:1) mixture at room temperature using 10 rapid,
      successive pressure cycles with N(2) attaining 1.0 MPa during compression was
      complete within 15 min. Using the new technique, consistently more PAHs and PCBs
      were extracted from the sediments in comparison to Soxhlet extraction. Extraction
      was evaluated according to key factors including the number of compression
      decompression cycles, compression pressure, sample amount, moisture, and
      pressurizing gas type. The heightened extraction performance was explained by
      cyclic changes in gas solubility during repetitive compression and decompression
      steps, which introduce mechanisms to fragment sediment aggregates resulting in
      increased contaminant exposure and extraction.

PMID- 19108863
TI  - Investigation of PCDD/Fs and dl-PCBs in fish from the southern Baltic Sea during
      the 2002-2006 period.
AB  - Concentrations of polychlorinated dibenzo-p-dioxins (PCDDs), polychlorinated
      dibenzofurans (PCDFs), and dioxin-like polychlorinated biphenyls (dl-PCBs) in the
      southern Baltic herring (Clupea harengus), sprat (Sprattus sprattus), and salmon
      (Salmo salar) are reported. The significant interspecies and season-specific
      differences in PCDD/Fs and dl-PCBs concentrations were observed. The contribution
      of dl-PCBs to the total toxicity equivalents (TEQs) ranged between 50% and 70%,
      dependently on fish species. In all samples, concentrations of PCDF were higher
      in comparison with that of PCDD. The permissible limits of the content of PCDD/Fs
      and dl-PCBs (8 pg g(-1) fresh weight for the sum of PCDD/Fs and dl-PCBs, and 4 pg
      g(-1) fresh weight for the PCDD/Fs) were exceeded mainly in salmon samples (in
      80% of salmon samples studied). The elevated levels of PCDD/F and dl-PCB were
      observed only in two of seventy two herring samples, and in ten of 62 sprat
      samples. The multiple regression analysis revealed that fish lipid content, and
      concentration of PCB 153, used simultaneously, might be useful in the prediction
      of TEQ values of fish samples. These two variables explained more than 80% of
      total variance. For all fish species studied, the correlation coefficients
      obtained with the multiple regression analysis were higher than that obtained
      with the regression analysis involving total TEQ values, and only one independent
      variable: fish lipid content.

PMID- 19108864
TI  - Isomers of Dechlorane Plus flame retardant in the eggs of herring gulls (Larus
      argentatus) from the Laurentian Great Lakes of North America: temporal changes
      and spatial distribution.
AB  - Dechlorane Plus (DP) is a chlorinated flame retardant (FR) comprised of two major
      structural isomers, syn and anti. For the Laurentian Great Lakes of North
      America, reports on DP have been limited to sediment and fish, not known for
      birds, and regardless temporal trends in Great Lakes wildlife is unknown. In the
      present study, syn- and anti-DP isomers were detected in egg pools spanning 1982
      2006 of a Great Lakes biomonitoring species, the herring gull (Larus argentatus),
      from seven colonies in the five Laurentian Great Lakes. The sum (Sigma) of syn-
      and anti-DP concentrations were generally <15 ng g(-1) wet weight (ww) and
      variable depending on the colonial site and year, although Sigma-DP
      concentrations were generally higher post mid-1990s for all sites. Syn- and anti
      DP concentrations ranged from 3.1 x 10(2) to 1.4 x 10(3)pg g(-1)ww and 1.3 x
      10(2) to 4.4 x 10(3)pg g(-1)ww, respectively. There was a weak but significant
      (r(S)=-0.31, p<0.001) negative relationship between the Sigma-DP concentration
      and the distance for the only DP production facility in North America at Niagara
      Falls, New York. However, the fraction of the anti-DP to the Sigma-DP
      concentration (f(anti)) was 0.69+/-0.08 (for all seven colonies and years, n=101
      pools), and there was no significant (r(S)=-0.18, p=0.07) negative relationship
      of f(anti) with increasing distance from the production facility at Niagara
      Falls, New York, which indicated that there was no temporal or spatial enrichment
      of either isomer relative to the commercial DP mixture. Over the past 25 years,
      it is clear that DP isomers have accumulated in the food web of female herring
      gulls with subsequent transfer during ovogenesis.

PMID- 19108865
TI  - Occurrence and possible sources of polychlorinated biphenyls in surface sediments
      from the Wuhan reach of the Yangtze River, China.
AB  - Twenty-seven surface sediment samples were collected from the mainstream and
      eight tributaries of the Wuhan reach of the Yangtze River, China, in 2005, in
      order to assess the distribution, possible sources, and potential risk of
      polychlorinated biphenyls (PCBs) in the environment. The total concentrations of
      PCBs (the sum of 39 congeners) ranged from 1.2 to 45.1 ng g(-1) dry weight, with
      a mean value of 9.2 ng g(-1). Sediment samples with the highest PCB
      concentrations came from the tributary sites, which are closer to PCB sources.
      Conversely, PCB concentrations in the sediment from the mainstream sites of
      Yangtze River were relatively low. The observed PCB levels were higher than those
      found in the sediments of other rivers in China, but lower than those in river
      sediments from other urban areas and harbors around the world. Low-chlorinated
      PCBs, dominated by tetra-PCBs and penta-PCBs, were identified as being prevalent
      in the surface sediments. Correlation analyses between the PCBs and the
      geochemistry and heavy metal content of the sediments suggest that the washing of
      these compounds from the land into the river by floods and heavy rains, or
      industrial wastewater and domestic sewage, may be the major sources of the PCBs.
      According to established sediment quality guidelines, the risk of adverse
      biological effects from the levels of PCBs recorded at most of the studied sites
      should be insignificant, although the higher concentrations at other sites could
      cause acute biological damage.

PMID- 19108866
TI  - The effect of acidification on the determination of elemental carbon, char-, and
      soot-elemental carbon in soils and sediments.
AB  - We studied the influence of acid pretreatment on the effective distinction
      between elemental carbon (EC) and organic carbon (OC), and between char-EC and
      soot-EC. Though widely employed in the pretreatment of soils and sediments for EC
      quantification, the use of HCl, HF, and HNO(3) could decrease soot thermal
      stability as acid remains, leading to an underestimation of soot-EC by thermal
      methods. We compared thermal optical reflectance (TOR) measurements of EC
      concentrations in char reference materials and in lacustrine and marine sediments
      following pretreatment with various acids. The results showed that pretreatment
      with 2M HCl, concentrated HNO(3), 7 M HNO(3), and 1 M HNO(3) did not result in EC
      oxidation. However, hot concentrated HNO(3) oxidized EC significantly, leading to
      lower concentrations of EC, char-EC and soot-EC. By comparing the removal of
      potentially interfering materials, which contain little fire-derived carbon, with
      different acid pretreatments, we recommend the HCl-HF-HCl and concentrated (not
      hot) HNO(3)-HF-HCl pretreatments for the determination of EC, char-EC, and soot
      EC in soils and sediments using the TOR method.

PMID- 19108867
TI  - Improved phytoremediation of oilseed rape (Brassica napus) by Trichoderma mutant
      constructed by restriction enzyme-mediated integration (REMI) in cadmium polluted
      soil.
AB  - In this study, oilseed rape (Brassica napus) was exploited in remediation of Cd
      contaminated soil in combination of Trichodermakoningii. To improve its
      phytoextracting efficiency, restriction enzyme-mediated integration was used to
      construct Trichoderma mutants with higher Cd resistance. Of 200 mutants, 10
      mutants were shown with higher Cd tolerance and enhanced ability of removing Cd
      from growth medium. In pot experiment, mutant P6 significantly alleviated the
      negative impacts of Cd on oilseed rape growth, and improved the Cd uptake ability
      of oilseed rape shoot in Cd contaminated soil (p<0.05). Based on the dry weight,
      the amounts of Cd in shoots of mutant P6 treated oilseed rape were increased by
      23% and 38% per pot compared with wild type Trichoderma treatment; 53% and 107%
      against non-inoculated treatment, respectively, at 20 and 50mgCdkg(-1) soil. The
      results suggested the Trichoderma mutant-oilseed rape symbiosis system could be
      used in remediation of soil contaminated with heavy metal Cd.

PMID- 19108868
TI  - Levels of polychlorinated dibenzo-p-dioxins, dibenzofurans, and biphenyls in
      southern Mississippi catfish and estimation of potential health risks.
AB  - Fish consumption has been classified as one of the primary pathways of exposure
      to polychlorinated dibenzo-p-dioxins, dibenzofurans (PCDD/Fs) and biphenyls
      (PCBs). In this study, we evaluated tissue levels of the 17 laterally substituted
      PCDD/Fs, 12 dioxin-like PCBs, and 97 non-dioxin-like PCBs in a number of wild
      caught and farm-raised catfish collected throughout southern Mississippi. Total
      lipid-adjusted TEQ and non-dioxin-like PCB concentrations in wild-caught catfish
      fillets were significantly higher than concentrations in farm-raised fillet
      samples. The percent contribution of PCDDs, PCDFs, and dioxin-like PCBs to mean
      total TEQ varied between wild-caught and farm-raised samples as well as by
      collection site for wild-caught catfish. The non-dioxin-like PCBs that
      contributed the most to total PCB concentrations also differed between wild
      caught and farm-raised samples. Regardless of whether samples were farm-raised or
      wild-caught, estimated cancer risks associated with consumption of these catfish
      were less than 27.0E-06. Overall, results of this study indicate that levels of
      dioxin-like compounds and PCBs in Mississippi catfish are similar to those
      measured in more recent studies in the US and that levels of these compounds
      appear to be decreasing in this food source.

PMID- 19108869
TI  - Leachates from plastic consumer products--screening for toxicity with Daphnia
      magna.
AB  - Plastic products can contain chemicals that are hazardous to human health and the
      environment. In this study, it was investigated if various plastic products emit
      hazardous chemical substances to water. Two leaching methods (batch and diffusion
      tests) were used and the leachates were tested for acute toxicity to Daphnia
      magna. Nine out of 32 tested plastic product leachates had Daphnia 48-h EC(50)s
      ranging from 5 to 80 g plastic material L(-1). For the remaining 23 products no
      effect on mobility was seen even at the highest test concentrations (70-100 g
      plastic material L(-1)). A compact disc (recordable) was the most toxic plastic
      product, but the toxicity was traced to the silver layer not the polycarbonate
      plastic material. The other products that displayed toxicity were made of either
      plasticized PVC (artificial leather, bath tub toy, inflatable bathing ring and
      table cloth) or polyurethane (artificial leather, floor coating and children's
      handbag). While the Toxicity Identification Evaluation (TIE) for compact discs
      using sodium thiosulfate addition showed that silver was causing the toxicity,
      the TIE for artificial leather using C18 cartridges showed that hydrophobic
      compounds were causing the toxicity. Acute toxicity tests of plastic product
      leachates were found to be useful for screening purposes for differentiating
      between toxic and non-toxic products.

PMID- 19108870
TI  - Polychlorinated biphenyls and thyroid hormones in adults: a systematic review
      appraisal of epidemiological studies.
AB  - Reported evidence regarding relationships between polychlorinated biphenyls
      (PCBs) and thyroid homeostasis in adults has been considered contradictory. The
      objective of this systematic review is to determine a possible association
      between PCB exposure and the circulating thyroid hormones and thyrotropin (TSH)
      levels in adults, by analyzing the quality of published studies. A systematic
      review of epidemiological papers was conducted using PubMed. An evaluation of the
      quality of 22 studies was performed, and the papers were classified into two
      tiers: Tier I for studies with higher quality scores (eight) and Tier II for
      studies with lower quality scores (14). It appears that PCBs can interfere with
      thyroid hormone homeostasis; however epidemiological evidence is not entirely
      clear. For triiodothyronine (T3) and thyroxine (T4), Tier I studies showed either
      an inverse (four cases for T3; five cases for T4) or no significant association
      (two cases for T3; five cases for T4) with PCBs. In the case of free thyroxine
      and TSH, the Tier I papers observed no clear association with PCB levels.
      Rigorous study design, assessment of potential confounding factors, and fuller
      reporting of methods and results in future studies will facilitate understanding
      of whether PCB exposure is associated with changes in thyroid function.

PMID- 19108871
TI  - Removal of ammonium chloride generated by ammonia slip from the SNCR process in
      municipal solid waste incinerators.
AB  - The selective non-catalytic reduction (SNCR) process is one of the methods used
      to reduce NO(x) to N(2) and H(2)O by injecting NH(3) or urea solution into a high
      temperature furnace. Merits of this method include simple handling, low cost, and
      energy savings. However, a critical problem of the SNCR process is the generation
      of ammonia slip; in reactions with HCl in flue gas, ammonium chloride is
      generated and forms detached white plumes near the stack. Using a laboratory
      scale experimental apparatus, we examined the possibility of NH(4)Cl collection
      and removal by a bag filter (BF). The molar NH(3)/HCl ratio of the compound
      collected at the filter was nearly one, regardless of gas temperature, retention
      time, and concentration, confirming the formation of NH(4)Cl. The NH(4)Cl
      generation ratio increased as reaction temperature decreased, indicating that the
      collection efficiency of NH(4)Cl should increase if the BF is operated at the
      lowest possible temperature while avoiding the critical point causing low
      temperature corrosion (e.g., 150 degrees C). In addition, the use of activated
      carbon injection in the front of the BF and the dust layer on the BF are expected
      to capture slipped ammonia at the BF and reduce NH(4)Cl fume generation in the
      stack.

PMID- 19108872
TI  - Characterization of medical waste from hospitals in Tabriz, Iran.
AB  - Medical waste has not received enough attention in recent decades in Iran, as is
      the case in most economically developing countries. Medical waste is still
      handled and disposed of together with domestic waste, creating great health risks
      to health-care stuff, municipal workers, the public, and the environment. A
      fundamental prerequisite for the successful implementation of any medical waste
      management plan is the availability of sufficient and accurate information about
      the quantities and composition of the waste generated. The objectives of this
      study were to determine the quantity, generation rate, quality, and composition
      of medial waste generated in the major city northwest of Iran in Tabriz. Among
      the 25 active hospitals in the city, 10 hospitals of different size,
      specializations, and categories (i.e., governmental, educational, university,
      private, non-governmental organization (NGO), and military) were selected to
      participate in the survey. Each hospital was analyzed for a week to capture the
      daily variations of quantity and quality. The results indicated that the average
      (weighted mean) of total medical waste, hazardous-infectious waste, and general
      waste generation rates in Tabriz city is 3.48, 1.039 and, 2.439 kg/bed-day,
      respectively. In the hospital waste studied, 70.11% consisted of general waste,
      29.44% of hazardous-infectious waste, and 0.45% of sharps waste (total hazardous
      infectious waste 29.89%). Of the maximum average daily medical waste, hazardous
      infectious waste, and general waste were associated with N.G.O and private
      hospitals, respectively. The average composition of hazardous-infectious waste
      was determined to be 35.72% plastics, 20.84% textiles, 16.70% liquids, 11.36%
      paper/cardboard, 7.17% glass, 1.35% sharps, and 6.86% others. The average
      composition of general waste was determined to be 46.87% food waste, 16.40%
      plastics, 13.33% paper/cardboard, 7.65% liquids, 6.05% textiles, 2.60% glass,
      0.92% metals, and 6.18% others. The average bulk densities of total medical
      waste, hazardous-infectious waste, and general waste were determined to be 99.58,
      96.16 and 101.26 kg/m3, respectively. Significant differences were observed
      between the medical waste characteristics of the hospitals studied here and those
      reported in other studies. In conclusion, the characteristics of generated
      medical waste, current environmental problems and strict budgets necessitate that
      the implementation of efficient management, training, and segregation program be
      top priorities if we are to minimize the treatment and disposal costs and reduce
      the risks of hazardous-infectious waste in Tabriz city.

PMID- 19108873
TI  - Effect of cadmium, lead and arsenic on the oviposition, hatching and embryonic
      survival of Biomphalaria glabrata.
AB  - Biomphalaria glabrata is a widespread freshwater gastropod mollusc. The easy
      aquaculture of these organisms allow its use as an accessible tool for
      contamination bioassays. B. glabrata showed marked metabolic responses when
      exposed to cadmium, lead and arsenic. Those responses could also affect the
      reproduction of the snails. Taking into account this hypothesis, B. glabrata were
      exposed for 96 h (acute laboratory bioassays) to different concentrations of
      cadmium (0.1, 0.05 and 0 mg/L), lead (0.5, 0.1, 0.05 and 0 mg/L) and arsenic
      (0.5, 0.1, 0.05 and 0 mg/L). Snails were removed from the aquaria while eggs were
      left in the same contaminant concentrations. The effect of the assayed toxicants
      on snail reproduction was registered as the alterations of the total number of
      laid eggs (TNLE), hatching time and embryonic survival. At 0.10 mg/L cadmium
      significantly decreased the TNLE (p<0.05) and no embryos survived. The lowest
      assayed level (0.05 mg/L) of cadmium, delayed the hatching time twice when it was
      compared with the control group (p<0.01). Lead decreased the TNLE at 0.5 mg/L
      level (p<0.01). The other assayed doses (0.05 and 0.10 mg/L) also decreased
      embryonic survival significantly (p<0.05 and p<0.01 respectively) and extended
      twice the time to hatching (p<0.01). The 0.50 mg/L level killed all embryos.
      Arsenic at all studied concentrations decreased the TNLE (p<0.05) while the
      hatching time was increased by 50%. Embryo survival only decreased at the highest
      level (0.5 mg/L) of arsenic assayed. In summary, the acute exposure (96 h) to
      cadmium lead and arsenic, altered the reproduction of B. glabrata, modifying the
      TNLE, hatching time and embryonic survival.

PMID- 19108874
TI  - Characterization of the intracellular signalling capacity of natural FXa mutants
      with reduced pro-coagulant activity.
AB  - INTRODUCTION: Factor X (FX) is a serine-protease playing a crucial role in the
      blood coagulation pathway and triggering intracellular signalling in a variety of
      cells via protease-activated receptors (PARs). By exploiting naturally occurring
      variants (V342A and G381D, catalytic domain; E19A, gamma-carboxyglutamic acid
      (GLA)-rich domain), we investigated the relationship between the pro-coagulant
      activity and the signal transduction capacity of FX. MATERIALS AND METHODS:
      Recombinant FX (rFX) variants were expressed in Human Embryonic Kidney cells and
      purified by immunoaffinity chromatography. Activated rFX (rFXa) variants were
      characterized for pro-coagulant, amidolytic and thrombin generation activity.
      rFXa signalling was assessed through evaluation of extracellular signal-regulated
      kinase 1 and 2 (ERK1/2) phosphorylation in C2C12 myoblasts. RESULTS AND
      CONCLUSIONS: rFX variants showed reduced (rFX-342A, 29%; rFX-19A, 12%) or not
      detectable (rFX-381D) amidolytic activity. Thrombin generation activity in a
      plasma system was also decreased either upon activation by Russell's viper venom
      (rFX-342A, 38%; rFX-19A, 7%; rFX-381D, not detectable) or by the extrinsic
      pathway (rFX-342A, 36%; rFX-19A, rFX-381D, not detectable). The rFXa-381D mutant
      displayed little or no enzymatic activity, and did not induce any appreciable
      signal transduction capacity. The rFXa-342A mutant induced a dose-dependent
      signalling with a 50% reduced signalling capacity. At the highest concentration
      (174 nM), signalling progressed with a time course similar to that of rFXa-wt.
      Zymogen rFX-19A showed defective and incomplete activation resulting in strongly
      reduced enzymatic activity and signalling. Taken together our data are consistent
      with a close correlation between pro-coagulant activity and intracellular
      signalling capacity.

PMID- 19108875
TI  - Expression of estrogen receptor-alpha and -beta and progesterone receptor-A and 
      B in a large cohort of patients with endometrioid endometrial cancer.
AB  - OBJECTIVE: The estrogen receptor (ER)-alpha and -beta and progesterone receptor
      (PR)-A and -B were determined in endometrioid endometrial cancer, and their
      prognostic values were assessed. METHODS: Tissue microarrays were constructed
      from 315 endometrioid endometrial cancer patients. Receptor expression was
      assessed by immunostaining, and their semi-quantitatively determined expression
      levels were correlated to classical clinico-histopathological parameters in
      addition to disease free and disease specific survival. RESULTS: Patients were
      classified as FIGO stage I (59.0%), stage II (17.1%), stage III (19.4%) and stage
      IV (4.1%). Sixty-five patients (20.6%) developed recurrent disease and 38 (12.1%)
      died due to endometrial cancer. In univariate analysis, expression of ER-alpha
      was related to early stage endometrial cancer (p=0.020), while expression of ER
      alpha, PR-A and PR-B was associated with lower grade tumours (p<0.0001, p<0.001
      and p=0.001 respectively). A ratio of ER-alpha/ER-beta <1 was related to a
      shorter disease free survival (p=0.027), while the ratio of PR-A/PR-B <1 both was
      associated with a shorter disease free survival as well as a shorter overall
      survival (p=0.044 and p=0.005, respectively). In early stage disease, using
      multivariate analysis, absence of ER-alpha was independently related to death of
      disease (p=0.017, OR 7.28, 95% CI 1.42-37.25), while absence of PR-A (p=0.015, OR
      4.2, 95% CI 1.32-13.33) appeared to be an independent prognostic factor for
      relapse of disease. CONCLUSION: We conclude that in early stage endometrioid
      endometrial cancer absence of PR-A is an independent prognostic factor for
      disease-free survival, while patients with ER-alpha positive tumours have a
      better overall survival.

PMID- 19108876
TI  - Maternal and perinatal outcomes of first pregnancy after chemotherapy for
      gestational trophoblastic neoplasia in Brazilian women.
AB  - OBJECTIVE: To evaluate maternal and perinatal outcomes of first pregnancy after
      chemotherapy for gestational trophoblastic neoplasia (GTN) in Brazilian patients.
      METHODS: This study included 252 subsequent pregnancies after chemotherapy for
      GTN treated between 1960-2005. Correlations of maternal and perinatal outcomes
      with chemotherapy regimen (single or multiagent) and the time interval between
      chemotherapy completion and first subsequent pregnancy were investigated.
      RESULTS: There was a significant increase in adverse maternal outcomes in women
      who conceived <6 months than 6-12 months (76.2% and 19.6%; p<0.0001; OR=13.12; CI
      95%=3.87-44.40) and >12 months (76.2% and 21.7%; p<0.0001; OR=11.56; CI 95%=3.98
      33.55) after chemotherapy. Spontaneous abortion frequency was higher <6 months
      (71.4%) than 6-12 months (17.6%; p<0.0001; OR=11.66; CI 95%=3.55-38.22) and >12
      months (9.4%; p<0.0001; OR=23.97; CI 95%=8.21-69.91) after chemotherapy. There
      was no difference in adverse perinatal outcomes (stillbirth, fetal malformation,
      and preterm birth) related to the interval after chemotherapy and subsequent
      pregnancy. The overall occurrence of adverse maternal and perinatal outcomes did
      not significantly differ between patients on single or multiagent regimens.
      CONCLUSION: Adverse maternal outcomes and spontaneous abortion were more frequent
      among patients who conceived within 6 months of chemotherapy completion. In these
      cases, careful prenatal monitoring and hCG level measurement 6 weeks after the
      completion of any new pregnancy are recommended.

PMID- 19108878
TI  - Risk factors for perinatal mortality in dairy cattle: cow and foetal factors,
      calving process.
AB  - It was the aim of this study to identify risk factors of perinatal mortality (PM)
      on a large dairy farm in Germany. Four hundred and sixty-three cows were observed
      continuously around calving. Data such as the lactation number, body condition
      score, pelvic measurements, duration of second stage of labour (SSL), degree of
      abdominal press (AP), presentation/position/posture of the calf, calving
      classification, various measurements of the calves and every action of the barn
      staff were documented. Calves born dead and those that died within 24h were
      classified as cases of PM. Logistic regression was performed to identify risk
      factors for the dependent variables PM, SSL and AP. 9.7% of all calves born
      (n=483) were classified as PM. In the logistic regression model, only SSL and
      presentation/position/posture of the foetus remained as significant effects for
      PM. The odds ratio for PM was 0.20, when SSL was < or =120 min, and 0.33, when
      the calves were born in anterior presentation, upper position and normal posture.
      With regard to SSL, primipara, insufficient AP, assisted calvings and as a trend,
      work shift changeover, these were risk factors for a prolonged SSL beyond 120
      min. The risk for insufficient AP was lower when the calves were born
      spontaneously, in anterior presentation and as single calves. In conclusion, the
      duration of SSL and presentation/position/posture of the calf seemed to be key
      risk factors for PM. Interventions should be considered when SSL lasts longer
      than 2h. Insufficient monitoring around parturition had a negative effect on the
      duration of SSL and thereby, indirectly on PM.

PMID- 19108877
TI  - A randomized phase III trial in advanced endometrial carcinoma of surgery and
      volume directed radiation followed by cisplatin and doxorubicin with or without
      paclitaxel: A Gynecologic Oncology Group study.
AB  - OBJECTIVES: After surgical debulking and volume-directed irradiation of the
      pelvis/para-aortic lymph nodes, treatment was randomized to compare recurrence
      free survival (RFS) and toxicity between two chemotherapy regimens for the
      treatment of women with advanced stage endometrial carcinoma. METHODS: Treatment
      was randomized between 6 cycles of cisplatin [C] (50 mg/m(2)) and doxorubicin [D]
      (45 mg/m(2)) with or without paclitaxel [P] (160 mg/m(2)). Initially in
      paclitaxel treated patients and, after May 2002, all patients received
      granulocyte growth factor with each cycle. RESULTS: Of 659 patients enrolled
      following surgery, 552 eligible patients were randomized to chemotherapy after
      irradiation. Accrual closed to Stage IV patients in June, 2003. Approximately 80%
      completed six cycles of chemotherapy. Three deaths resulted from bowel
      complications and one death was due to renal failure. Hematologic adverse events,
      sensory neuropathy and myalgia, were more frequent and severe in the paclitaxel
      arm (p<0.01) which was confirmed by Quality of Life assessments. Percentage of
      patients alive and recurrence-free at 36 months was 62% for CD vs. 64% for CDP.
      The hazard of recurrence or death relative to the CD arm stratified by stage is
      0.90 (95% CI is 0.69 to 1.17, p=0.21, one-tail). However, in subgroup analysis,
      CDP was associated with a 50% reduction in the risk of recurrence or death among
      patients with gross residual disease (95% CI: 0.26 to 0.92). Stage, residual
      disease, histology/grade, positive para-aortic node and cytology, pelvic
      metastases and age were significantly associated with RFS. CONCLUSION: The
      addition of paclitaxel to cisplatin and doxorubicin following surgery and
      radiation was not associated with a significant improvement in RFS but was
      associated with increased toxicity.

PMID- 19108879
TI  - Rhodiola sacra aqueous extract (RSAE) improves biochemical and sperm
      characteristics in cryopreserved boar semen.
AB  - Although Rhodiola sacra aqueous extract (RSAE) has been used in many studies as
      an antioxidant, its effects on semen characteristics and its antioxidant
      properties during cryopreservation of boar sperm have never been evaluated. Semen
      was collected from five Duroc boars (2-4-year-old) twice weekly and frozen-thawed
      in extender with RSEA. Motion characteristics were assessed with a computer-aided
      semen analysis (CASA) system, whereas other sperm quality end points were
      assessed by routine methods. The effective concentration of RSEA in extender
      ranged from 4 to 8mg/L and the effect of RSEA on sperm quality was better in
      glycerol-free extender than extender containing glycerol (P<0.05). In frozen
      thawed boar semen, there was a direct correlation (P<0.05) between RSEA
      concentration and glutathione (GSH) concentrations, mitochondrial activity, and
      hypoosmotic swelling test (HOST), and an inverse correlation (r=-0.982, P<0.05)
      between RSEA concentration and malondialdehyde (all end points were significantly
      higher at 6mg/L than in the control group). In summary: (i) the effective
      concentration of RSEA in extender ranged from 4 to 8mg/L; (ii) the effect of RSEA
      on sperm quality was better in extender without glycerol; and (iii) there was a
      significant correlation between RSEA concentrations and concentrations of GSH and
      MAD in frozen-thawed boar semen (antioxidant effects of RSEA were concentration
      dependent). Further studies are needed to define the active ingredient in RSEA
      that protects boar sperm against ROS.

PMID- 19108880
TI  - Cytochrome P450 2C19 polymorphism in young patients treated with clopidogrel
      after myocardial infarction: a cohort study.
AB  - BACKGROUND: Clopidogrel and low-dose aspirin have become the mainstay oral
      antiplatelet regimen to prevent recurrent ischaemic events after acute coronary
      syndromes or stent placement. The frequent genetic functional variant 681 G>A
      (*2) of cytochrome P450 2C19 (CYP2C19) is an important contributor to the wide
      variability between individuals of the antiplatelet effect of clopidogrel. We
      assessed whether the CYP2C19*2 polymorphism affected long-term prognosis of
      patients who were chronically treated with clopidogrel. METHODS: Between April 1,
      1996, and April 1, 2008, 259 young patients (aged <45 years) who survived a first
      myocardial infarction and were exposed to clopidogrel treatment for at least a
      month, were enrolled in a multicentre registry and underwent CYP2C19*2
      determination. The primary endpoint was a composite of death, myocardial
      infarction, and urgent coronary revascularisation occurring during exposure to
      clopidogrel. Follow-up was every 6 months. The key secondary endpoint was stent
      thrombosis proven by angiography. FINDINGS: Median clopidogrel exposure time was
      1.07 years (IQR 0.28-3.0). Baseline characteristics were balanced between
      carriers (heterozygous *1/*2, n=64; homozygous *2/*2, n=9) and non-carriers
      (n=186) of CYP2C19*2 variant. The primary endpoint occurred more frequently in
      carriers than in non-carriers (15 vs 11 events; hazard ratio [HR] 3.69 [95% CI
      1.69-8.05], p=0.0005), as did stent thrombosis (eight vs four events; HR 6.02
      [1.81-20.04], p=0.0009). The detrimental effect of the CYP2C19*2 genetic variant
      persisted from 6 months after clopidogrel initiation up to the end of follow-up
      (HR 3.00 [1.27-7.10], p=0.009). After multivariable analysis, the CYP2C19*2
      genetic variant was the only independent predictor of cardiovascular events (HR
      4.04 [1.81-9.02], p=0.0006). INTERPRETATION: The CYP2C19*2 genetic variant is a
      major determinant of prognosis in young patients who are receiving clopidogrel
      treatment after myocardial infarction.

PMID- 19108881
TI  - Vaccine coverage and the GAVI Alliance Immunization Services Support initiative.

PMID- 19108882
TI  - Clopidogrel in acute coronary syndrome: to genotype or not?

PMID- 19108883
TI  - Measurement of immunisation coverage.

PMID- 19108884
TI  - Multi-layered culture of human skin fibroblasts and keratinocytes through three
      dimensional freeform fabrication.
AB  - We present a method to create multi-layered engineered tissue composites
      consisting of human skin fibroblasts and keratinocytes which mimic skin layers.
      Three-dimensional (3D) freeform fabrication (FF) technique, based on direct cell
      dispensing, was implemented using a robotic platform that prints collagen
      hydrogel precursor, fibroblasts and keratinocytes. A printed layer of cell
      containing collagen was crosslinked by coating the layer with nebulized aqueous
      sodium bicarbonate. The process was repeated in layer-by-layer fashion on a
      planar tissue culture dish, resulting in two distinct cell layers of inner
      fibroblasts and outer keratinocytes. In order to demonstrate the ability to print
      and culture multi-layered cell-hydrogel composites on a non-planar surface for
      potential applications including skin wound repair, the technique was tested on a
      poly(dimethylsiloxane) (PDMS) mold with 3D surface contours as a target
      substrate. Highly viable proliferation of each cell layer was observed on both
      planar and non-planar surfaces. Our results suggest that organotypic skin tissue
      culture is feasible using on-demand cell printing technique with future potential
      application in creating skin grafts tailored for wound shape or artificial tissue
      assay for disease modeling and drug testing.

PMID- 19108885
TI  - Bacterial and mammalian cell response to poly(3-sulfopropyl methacrylate) brushes
      loaded with silver halide salts.
AB  - This study investigates the antibacterial and cytotoxic effect of surfaces with
      sulphonate brushes containing silver salts. By using the same type of samples for
      both cytotoxicity and antibacterial studies, these two parameters could be
      compared in a controlled way. The silver was incorporated into the brush in four
      different forms to enable release of silver ions at different concentrations and
      different rates. It was found that although the surfaces displayed very good
      antibacterial properties in buffer solutions, this effect disappeared in systems
      with high protein content. Similarly, the silver-containing surfaces displayed
      cytotoxic effects in the absence of serum proteins but this effect was reduced in
      the presence of serum. The speciation of silver in the different solutions is
      discussed. Cytotoxic and antibacterial effects are compared at the different
      silver concentrations released. The implications of a concentration range where
      silver could be used to kill bacterial without harmful effects on mammalian cells
      are also discussed and questioned.

PMID- 19108886
TI  - Quantification of feto-fetal transfusion rate through a single placental arterio
      venous anastomosis in a monochorionic twin pregnancy.
AB  - Twin-to-twin transfusion syndrome (TTTS) is due to unbalanced inter-twin blood
      flow through placental vascular anastomoses. We present a TTTS-case treated with
      fetoscopic laser surgery that allowed us to calculate the net inter-twin blood
      flow. In the weeks following laser treatment, the ex-recipient developed severe
      fetal anemia and was treated with two intrauterine adult red cell transfusions
      (at 26 and 29 weeks' gestation, respectively). After birth, placental injection
      with color-latex identified a single residual arterio-venous anastomosis from the
      ex-recipient to the ex-donor. We measured the fetal and adult hemoglobin
      concentrations in the anemic fetus before and after both intrauterine
      transfusions, and in both twins at birth. On the basis of these measurements, we
      calculated the blood flow across the residual arterio-venous anastomosis and
      found it to be 5.8+/-1.5 mL/24h after the 1st transfusion and 11.4+/-2.9 mL/24h
      after the 2nd transfusion.

PMID- 19108887
TI  - Increasing the BCR-ABL expression levels and/or the occurrence of ABL point
      mutations does not always predict resistance to Imatinib Mesylate in BCR-ABL
      positive acute lymphoblastic leukemia.

PMID- 19108888
TI  - In vitro biology of human myeloid leukemia.
AB  - For about 40 years, the biology of human myeloid leukemia (ML) has been studied
      in different in vitro systems. Throughout this time, semisolid colony assays,
      Dexter-type long-term cultures and liquid suspension cultures have contributed to
      our understanding of the mechanisms involved in the origin and progression of
      this hematological disorder. By using such systems, it has been possible to
      identify the cells in which leukemia originates; to recognize a functional
      hierarchy within the hematopoietic system of leukemia patients; to identify
      factors, soluble and cell-associated, that regulate leukemic growth; and to study
      the effects of different antineoplastic drugs. Furthermore, in vitro systems for
      purging of leukemic cells have been developed. Still, many questions and problems
      remain unsolved regarding the biology of myeloid leukemia in vitro. This article
      presents a comprehensive review on the behavior of leukemic stem and progenitor
      cells, both from acute and chronic myeloid leukemia, in the different culture
      systems mentioned above.

PMID- 19108889
TI  - A phase I trial of continuous infusion of the multidrug resistance inhibitor
      zosuquidar with daunorubicin and cytarabine in acute myeloid leukemia.
AB  - Zosuquidar is a potent and specific inhibitor of P-glycoprotein (P-gp). In
      preliminary experiments, blockade of P-gp for at least 12 h was required to
      reverse daunorubicin resistance. Because of the short half-life of zosuquidar, we
      performed a phase I trial of this drug as a 72-h infusion (CIV) in 16 patients
      during leukemic induction with daunorubicin and cytarabine. Study goals were to
      establish safety and determine the dose required for P-gp inhibition in NK cells
      and AML blasts. > 90% P-gp inhibition was achieved within 2h at a plasma
      threshold of 132 ng/ml zosuquidar. The recommended phase II dose of zosuquidar is
      700 mg/day.

PMID- 19108890
TI  - Management of conjunctival chemosis secondary to imatinib treatment for chronic
      myelogenous leukemia.

PMID- 19108891
TI  - Epigenetic control of differential expression of specific ERG isoforms in acute T
      lymphoblastic leukemia.
AB  - Expression of ERG is of prognostic significance in acute myeloid leukemia (AML)
      and T-lymphoblastic leukemia (T-ALL) pointing to its role in leukemogenesis. To
      unravel its transcriptional regulation we analyzed the expression of ERG specific
      isoforms. Expression of the two main isoforms ERG2 and ERG3 was found in AML and
      normal CD34+ cells, whereas T-ALL blasts only expressed ERG isoforms harboring
      exon 5 (ERG3) lacking expression of ERG2. Bisulfite sequencing revealed
      hypermethylation of a CpG island within the ERG2 promoter region in T-ALL.
      Treatment of the T-lymphoblastic cell line BE13 with decitabine led to re
      expression of ERG2 and pyrosequencing showed concordant DNA hypomethylation, thus
      confirming a methylation regulated expression of ERG2. Moreover, the
      identification of a new ERG isoform (ERG3Deltaex12) suggests the association with
      different interaction partners and adds to the complexity of downstream pathways
      mediated by the expression of specific ERG transcripts in acute leukemia.

PMID- 19108892
TI  - Do you smell what I smell? Olfactory impairment in wild yellow perch from metal
      contaminated waters.
AB  - In this study, we sampled yellow perch from three lakes along a metal
      contamination gradient and examined their olfactory ability in response to
      conspecific chemical alarm cues and metal-binding characteristics of their
      olfactory epithelium (OE). We measured the electrophysiological response at the
      OE, tested their antipredator behaviour and measured neuronal density at the
      olfactory rosette and bulb. Yellow perch from contaminated lakes exhibited
      significantly larger electrophysiological responses to alarm cues than clean lake
      fish, but showed no antipredator behaviour contrary to clean lake fish. Neuron
      density did not differ at either the olfactory rosette or bulb between clean and
      contaminated fish. Unlike fishes raised under laboratory or aquaculture settings,
      fish from contaminated lakes possessed a functional OE after metal exposure, but
      similar to laboratory/aquaculture fishes, yellow perch did not exhibit olfactory
      mediated behaviours. Thus, wild fish from contaminated lakes can detect chemical
      stimuli but olfactory signal processing is disrupted which could alter ecological
      functioning.

PMID- 19108893
TI  - Role of antioxidants in Cr tolerance of three crop plants: Metal accumulation in
      seeds.
AB  - Pot experiments were conducted on three crop plants (Vigna radiata cv. PDM54, V.
      radiata cv. NM1, Brassica juncea cv. vaibhav) which were grown on six different
      tannery sludge (TS) amendments. The translocation of Cr to the seeds was found to
      be higher in B. juncea than the two cultivars of V. radiata, and their levels
      were below detectable limits in all the three plants grown on lower amendments of
      tannery sludge (T10 and T25). There was a gradual increase in protein content and
      antioxidant levels in all the plants grown on lower sludge amendments. However,
      the levels of all the antioxidants were higher in B. juncea than the two
      cultivars of V. radiata. The increase in malondialdehyde content of B. juncea was
      lower than the two cultivars of V. radiata as compared to their respective
      controls. Overall, the plants of B. juncea have shown better tolerance than both
      the cultivars of V. radiata.

PMID- 19108894
TI  - Effects of the polycyclic musk HHCB on individual- and population-level endpoints
      in Potamopyrgus antipodarum.
AB  - Although the polycyclic musk 1,3,4,6,7,8-hexahydro-4,6,6,7,8,8
      hexamethylcyclopenta[gamma]-2-benzopyran (HHCB) is frequently detected in aquatic
      sediments, very little is known about its effects on sediment-feeding organisms.
      Effects of sediment-associated HHCB on growth, feeding rate, survival and
      reproduction in the gastropod Potamopyrgus antipodarum were measured in the
      laboratory. Snails were exposed to six nominal HHCB concentrations: 0, 0.1, 1,
      10, 30 and 100microg g(-1) dry weight (dw) sediment. Adult survival and growth
      were not affected by HHCB. However, juvenile growth and survival, reproduction,
      time to first reproduction and adult feeding rate were more sensitive endpoints
      and declined with increasing HHCB concentration. Individual-level endpoints for
      P. antipodarum were integrated into a population model to investigate the effects
      of HHCB on population growth rate. Under otherwise favorable laboratory
      conditions, population growth rate was slightly (by ca. 2%), but not
      significantly, reduced with increasing HHCB exposure concentration. Model
      simulations were performed to explore the consequences of HHCB exposure under
      more ecologically realistic conditions (i.e., survival and reproduction of
      unexposed snails were markedly reduced relative to the laboratory). The results
      suggest that despite detectable effects of HHCB on individual-level endpoints
      measured in the laboratory, impacts on population dynamics of this deposit feeder
      are not likely to occur at environmentally relevant exposure concentrations.

PMID- 19108895
TI  - Trypanosoma cruzi calreticulin: a possible role in Chagas' disease autoimmunity.
AB  - Trypanosoma cruzi (T. cruzi) is the causative agent of Chagas' disease, an
      endemic and chronic illness that affects 18 million people in Latin America. The
      mechanisms underlying its pathogenesis are controversial. There is a growing body
      of evidence supporting the view that T. cruzi infection elicits severe autoimmune
      responses in the host, which significantly contribute to the pathogenesis of
      Chagas' disease, and several recent studies have reported the presence of
      autoantibodies and effector T lymphocytes against parasite and self antigens in
      infected patients and experimentally infected animals. T. cruzi calreticulin
      (TcCRT) is a 45kDa protein, immunogenic in humans, rabbits and mice. It has a
      high degree of homology with human (HuCRT) and mouse calreticulin (MoCRT), which
      would explain why an immune response to TcCRT could contribute to autoimmune
      reactions in Chagas' disease. Anti-TcCRT antibodies generated in A/J mice
      immunized with recombinant TcCRT (rTcCRT) reacted with rHuCRT and bound to
      neonatal and adult isogenic cardiomyocytes cultured in vitro. Interestingly,
      histological alterations, such as edema formation and cell infiltrates, which
      include CD3(+) cells, were detected in heart sections from immunized animals.
      Therefore, in rTcCRT-immunized mice, an autoimmune reaction against host CRT,
      paralleled by histological cardiac alterations, suggests a role of the parasite
      molecule in the induction of immunologically mediated heart tissue damage. The
      data presented here propose that TcCRT participates in the induction of cardiac
      autoimmunity in Chagas' disease.

PMID- 19108896
TI  - Calreticulin from the intestinal nematode Heligmosomoides polygyrus is a Th2
      skewing protein and interacts with murine scavenger receptor-A.
AB  - Helminth infections are commonly associated with a Th2 immune response, yet only
      a few parasite molecules involved in triggering such immune responses have been
      identified. Here, we describe the Th2-skewing property of calreticulin of
      Heligmosomoides polygyrus (HpCRT). HpCRT is a secreted protein most abundantly
      expressed by tissue invasive larvae (L4). Native HpCRT purified from adult worm
      extract (nHpCRT) stimulated robust IL-4 release from CD4(+) T cells of H.
      polygyrus infected mice. Interestingly, CD4(+) T cells also produced significant
      amounts of IL-10 while IFN-gamma was not detectable. Likewise, immunization with
      recombinant HpCRT (rHpCRT) without extrinsic adjuvant led predominantly to a
      specific IL-4 production implying the innate ability of HpCRT to drive Th2
      responses. The triggering of a Th2-skewed immune response to rHpCRT is
      corroborated by the induction of HpCRT-specific IgG1 and IgE antibodies.
      Furthermore, rHpCRT bound to scavenger receptor type A (SR-A) on dendritic cells,
      and interaction of HpCRT with SR-A led to internalization of HpCRT that could be
      partially blocked by competition with SR-A ligands as well as with an anti-SR-A
      monoclonal antibody. Hence, our data imply that nematode calreticulin interacts
      with a mammalian scavenger receptor and at the same time induces a Th2 response.

PMID- 19108898
TI  - Long term augmentation with T3 in refractory major depression.
AB  - BACKGROUND: The addition of triiodothyronine (T(3)) is one of the most widely
      studied augmentation strategies for refractory depression. Despite this there are
      no long term studies or studies of doses above 100 mcg. METHOD: Long term and
      high dose augmentation with T(3) for refractory unipolar major depression was
      studied. Seventeen patients were assessed for symptom improvement with the
      Clinical Global Impression of Improvement Scale. RESULTS: Fourteen of 17 patients
      showed improvement. One patient saw no improvement and 2 dropped out due to side
      effects. The patients who benefited showed an average CGI improvement of 2.5 (SD:
      0.52). The average dose used was 80 mcg (SD: 30.2, range: 25 mcg-150 mcg). The
      average length of time on T(3) was 24.2 months (SD: 19.4, range: 11.8-86.7). This
      case series shows that T(3) may be successfully employed as a long term treatment
      augmentation of major depression if over time dosage levels are increased beyond
      the traditional 50 mcg.

PMID- 19108897
TI  - Iron-binding and anti-Fenton properties of baicalein and baicalin.
AB  - Baicalein and baicalin, the major bioactive compounds found in the Chinese herb
      Scutellaria baicalensis, have been shown to be effective against cancer,
      bacterial infections and oxidative stress diseases. However, little is known
      about their mechanisms of action. To probe whether iron homeostasis modulation
      may play a role in their bioactivity, we have investigated their iron binding
      characteristics under physiologically relevant conditions. A 2:1 baicalein
      ferrous complex was readily formed in 20mM phosphate buffer, pH 7.2, with a
      binding constant approximately 2-9 x 10(11)M(-2), whereas a 1:1 baicalein-ferric
      complex was formed, under the same conditions, with an apparent binding constant
      approximately 1-3 x 10(6)M(-1). Baicalein appears to bind the ferrous ion more
      strongly than ferrozine, a well known iron(II) chelator. Using (1) H NMR and
      Zn(2+) and Ga(3+) as probes, the iron-binding site on baicalein was elucidated to
      be at the O6/O7 oxygen atoms of the A-ring. No binding was observed for baicalin
      under the same NMR conditions. Furthermore, baicalein strongly inhibits the Fe
      promoted Fenton chemistry via a combination of chelation and radical scavenging
      mechanism while baicalin can provide only partial protection against radical
      damage. These results indicate that baicalein is a strong iron chelator under
      physiological conditions and hence may play a vital role in modulating the body's
      iron homeostasis. Modulation of metal homeostasis and the inhibition of Fenton
      chemistry may be one of the possible mechanisms for herbal medicine.

PMID- 19108899
TI  - Inflammatory and redox status of ponies with a history of pasture-associated
      laminitis.
AB  - Inflammatory and redox signals could render lamellar tissue susceptible to damage
      and contribute to higher risk for laminitis in obese or insulin resistant ponies
      just as these factors contribute to health risks in humans with metabolic
      syndrome. This study evaluated circulating markers of inflammatory and redox
      status in ponies that had a history of recurrent bouts of pasture-associated
      laminitis (PL, n = 42) or had never developed clinical laminitis (NL, n = 34)
      under the current management conditions. There were no differences (P > 0.05)
      between PL and NL ponies for markers of antioxidant function (glutathione,
      glutathione peroxidase, superoxide dismutase) or increased oxidative pressure
      (malondialdehyde, apoptosis, 3-nitrotyrosine). Inflammatory status, as indicated
      by fibrinogen concentration, was also not different between pony groups (P =
      0.84). However, PL ponies had higher (P < 0.001) plasma concentrations of the pro
      inflammatory cytokine TNF-alpha than NL ponies. This suggests that a
      predisposition to laminitis is associated with increased circulating inflammatory
      cytokines. TNF-alpha could also represent a contributing factor to increased
      insulin resistance observed in laminitis prone ponies. These results provide new
      insight into potential mechanisms and risk factors underlying laminitis.

PMID- 19108900
TI  - Endotoxin-induced activation of equine digital vein endothelial cells: role of
      p38 MAPK.
AB  - The endothelium plays a major role in the pathogenesis of endotoxemia. Binding of
      endotoxin (lipopolysaccharide; LPS) to endothelium initiates a range of
      signalling events, including activation of p38 mitogen activated protein kinases
      (MAPKs) that are involved in the initiation of inflammatory responses. In the
      present study we have examined whether clinically relevant concentrations of LPS
      can activate p38 MAPK in equine endothelial cells and have investigated the role
      of the kinase in neutrophil adhesion and mediator release. Cultured equine
      digital vein endothelial cells (EDVEC) were exposed to LPS and phosphorylation of
      p38 MAPK was assessed by Western blotting using phospho-specific antibodies.
      Neutrophil adhesion was quantified by assaying myeloperoxidase and the release of
      prostacyclin (PGI(2)) was measured by radioimmunoassay of its stable breakdown
      product 6-keto-PGF(1alpha). The effects of the p38 MAPK inhibitors, SB203580 and
      PD169316, on neutrophil adhesion and 6-keto-PGF(1alpha) release were examined, as
      was the effect of an anti-E-selectin antibody on neutrophil adhesion to LPS
      activated EDVEC. LPS treatment significantly increased p38 MAPK phosphorylation,
      which was maximal after a 1h LPS incubation using a concentration of 10(-5)g/ml
      (EC(50) = 2 x 10(-7)g/ml). Neutrophil adhesion to LPS-stimulated endothelial
      cells (maximal at 10(-6)g/ml; EC(50) = 6 x 10(-10)g/ml) was significantly
      inhibited in the presence of p38 MAPK inhibitors (reduced from a maximum of 33+/
      6% to 13+/-4% adhesion at 10(-6)M SB203580 and to 21+/-4% adhesion at 10(-6) M
      PD169316), or an anti-E-selectin antibody (reduced from 17+/-1% adhesion to 6+/
      1% adhesion). 6-keto-PGF(1alpha) release was increased in a concentration
      dependent manner following LPS exposure (maximal at 10(-6)g/ml; EC(50) = 1 x 10(
      9)g/ml), and was significantly inhibited by p38 MAPK blockade (reduced from 1.6+/
      0.3 x 10(-9)g/ml to 4+/-1 x 10(-10)g/ml and 4+/-2 x 10(-10)g/ml with 10(-6) M
      SB203580 or 10(-6) M PD169316, respectively). This study has demonstrated that
      clinically relevant concentrations of LPS activate p38 MAPK in equine endothelial
      cells and that both neutrophil adhesion to LPS-activated EDVEC and PGI(2) release
      are dependent upon p38 MAPK phosphorylation. These results reveal a key role for
      p38 MAPK in the response of the endothelium to LPS and suggest that inhibition of
      this kinase may reduce inflammatory events in the endotoxemic horse.

PMID- 19108901
TI  - Effects of intrauterine and extrauterine exposure to GSM-like radiofrequency on
      distortion product otoacoustic emissions in infant male rabbits.
AB  - OBJECTIVES: The aim of this study was to investigate the potential hazardous
      effects of intrauterine (IU) and/or extrauterine (EU) exposure to 1800 MHz Global
      System for Mobile Communications-like (GSM-like) radiofrequency (RF) on the
      cochlear functions of infant rabbits by measuring distortion product otoacoustic
      emission (DPOAE) response amplitudes. METHODS: Thirty-six white infant male New
      Zealand rabbits each 1-month-old were included in the study. The animals were
      randomly divided into four groups. Nine infant rabbits (Group 1) were not exposed
      to 1800 MHz GSM-like RF (Control-C). Nine infant rabbits (Group 2) were exposed
      to 1800 MHz GSM-like RF, 15 min daily for 14 days after they reached 1-month of
      age (extrauterine-EU). Nine infant rabbits (Group 3) were exposed to 1800 MHz GSM
      like RF, 15 min daily for 7 days in the intrauterine period (between 15th and
      22nd days of the gestational period) (intrauterine-IU). Nine infant rabbits
      (Group 4) were exposed to 1800 MHz GSM-like RF, 15 min daily for 7 days in the
      intrauterine period (between 15th and 22nd days of the gestational period) and 15
      min daily for 14 days after they reached to 1-month of age (IU+EU). The cochlear
      functions were assessed by DPOAEs at 1.0-8.0 kHz. RESULTS: At 1.5 kHz, the mean
      DPOAE amplitude of Group 3 was higher than that of the controls and Group 2; and
      the mean DPOAE value of Group 4 was higher than that of the controls and Group 2.
      At 2.0 kHz, the mean DPOAE amplitude of Group 4 was higher than that of Group 2.
      At 3.0 kHz, the mean DPOAE amplitude of Group 4 was higher than that of the
      controls and Group 2. At 4.0 kHz, the mean DPOAE amplitude of Group 2 was lower
      than that of the controls, while the mean value of Group 4 was higher than the
      mean value of the controls and Group 2. At 6.0 kHz, the mean DPOAE amplitude of
      Group 2 was lower than that of the control group; however, the mean value of
      Group 4 was higher than that of Group 2. At 1.0 and 8.0 kHz, no significant
      differences were found among the four groups. CONCLUSION: Prolonged exposure and
      hyperthermia related to the power density of applied RF, increasing the
      temperature in the ear canal, may affect DPOAE amplitudes. Harmful effects of RF
      are mainly observed as a decrease in DPOAE amplitudes at 4.0-6.0 kHz during
      extrauterine exposure in infancy. During the intrauterine period, the water
      content of the middle and inner ear and amnion fluid may play a protective role.
      Therefore, children must be protected from RF exposure. The use of mobile phones
      at short distances from the ear of the infants should be avoided because of the
      lower thickness of the anatomical structure in infancy.

PMID- 19108902
TI  - Quality of life in children with chronic suppurative otitis media with or without
      cholesteatoma.
AB  - OBJECTIVE: To validate a disease-specific health related quality of life (HRQOL)
      instrument for children with chronic suppurative otitis media with or without
      cholesteatoma. METHODS: Caregivers of 45 children with chronic suppurative otitis
      media, who were offered an operation (tympanoplasty or radical mastoidectomy) in
      a tertiary children's hospital, were administered a 5-item quality of life survey
      (COM-5) The COM-5, which is a modified version of OM-6, was administered four
      times: few weeks and few days before operation and six months and one year
      postoperatively. Psychometric characteristics and more specifically test-retest
      reliability, internal consistency, construct validity, and responsiveness to
      clinical change of the COM-5 score were the main outcome measures. RESULTS:
      Median COM-5 score was 2.6 (1- to 7-point scale) with higher scores indicating
      poorer quality of life. Test-retest reliability was good (interclass correlation
      coefficient=0.73) Construct validity was demonstrated by significant correlations
      between COM-5 score and global ear-related quality of life (R=-0.485), between
      physical suffering and ear-related physician visits (R=0.41) and between
      caregiver concerns vs ear-related physician visits (R=0.44). The mean change in
      COM-5 score after successful tympanoplasty was 1.1 and correlated well with the
      change of global ear-related quality of life rating (R=-0.545) as well as with
      the degree of clinical change reported by the caregiver (R=0.494). The mean
      standardized response was 1.3 after tympanoplasty indicating the instrument's
      large responsiveness to clinical change after this procedure, but only 0.7 after
      radical mastoidectomy. CONCLUSIONS: The COM-5 is a valid, reliable and responsive
      instrument. Apart from its satisfactory psychometric characteristics, it can be
      easily administered in caregivers of children who require a tympanoplasty due to
      chronic suppurative otitis media.

PMID- 19108903
TI  - Gastroesophageal reflux and obstructive sleep apnea in childhood.
AB  - OBJECTIVES: To examine the relationship between gastroesophageal reflux (GER) and
      obstructive sleep apnea syndrome (OSAS) with polysomnographic alterations and
      symptom severity. PATIENTS AND METHODS: Eighteen children aged from 6 to 12 years
      (8.14+/-1.75) with adenotonsillar hypertrophy and OSAS were evaluated with the
      OSA-18 questionnaire nasofibrolaringoscopy and full overnight polysomnography
      performed simultaneously with esophageal pH monitoring. RESULTS: OSAS (Apnea
      index (AI)>or=1/hour) was present in all cases. Reflux parameters did not
      correlate to OSAS severity and a temporal relationship between GER and apnea
      hypopnea events was not observed. Body mass index was lower than 18 in 9 cases
      (52.9%) and 7 children (41.1%) presented a history of abnormal behavior during
      sleep. In most cases oxygen desaturation and reduction of sleep efficiency were
      mild. Sleep architecture was similar to the young adult pattern. Seven children
      (41.1%) presented pH monitoring values below 4 during more than 10% of total
      sleep time. pH monitoring values were correlated to emotional distress (p=0.008)
      and to daytime problems (p=0.03) as evaluated by the OSA-18. CONCLUSIONS: GER is
      frequent and should be assessed in children from 6 to 12 years with OSAS.
      Emotional distress and daytime problems are correlated to increased GER severity.

PMID- 19108904
TI  - Urinary incontinence (UI) and quality of life (QoL) of the elderly residing in
      residential homes in Turkey.
AB  - The objective of this study was to evaluate urinary incontinence (UI) and its
      effect on the quality of life (QoL) of older people dwelling in residential homes
      in Turkey. A cross-sectional study was applied in residential homes. A total of
      1110 people older than 60 years residing in five selected residential homes were
      studied. An interview was conducted with the residents who had sufficient
      cognitive function and agreed to participate. The QoL and the mental and the
      functional state of the residents were analyzed using the King's Health
      Questionnaire (KHQ), Mini Mental State Examination (MMSE), and the Rankin Scale,
      respectively: Of the total pool, 694 residents were included in the study of
      which 56.48% (n=392) were female and 43.52% (n=302) were male. UI was present in
      170 women and 63 men. Pad usage was more common in women (88%) than that in men
      (29.1%). The QoL subdimensions showed that women had higher scores than men. Urge
      UI (UUI) had more impact on the QoL than that on functional, mixed or stress
      incontinence. We concluded that UI negatively affects the QoL of older people
      living in residential homes. In particular, women and patients suffering from UUI
      are more severely affected.

PMID- 19108905
TI  - Adiposity parameters and cognitive function in the elderly: application of "Jolly
      Fat" hypothesis to cognition.
AB  - Obesity has a strong association with cardiovascular and metabolic diseases,
      which have also been linked with dementia. While recent studies have reported an
      association between mid-life obesity and dementia, the role that later-life
      obesity may have is less clear. A total of 721 community-dwelling elderly (60-85
      years old) were selected. Obesity parameters, like body mass index (BMI), waist
      hip ratio (WHR), waist circumference (WC), and percent body fat (PBF), as well as
      cognitive functions were measured over a period of approximately 2 years, and
      then the relationships between these variables were assessed. The change in
      cognitive function in the elderly was associated with the baseline assessment of
      BMI (linearly, beta=0.092), WC (quadratic, beta=1.333), and PBF (linearly,
      beta=0.097). Using multiple regression analyses, the differences exist in the
      change of cognitive function over time according to the sex. For men, increased
      obesity over time when obese in the baseline assessment (BMI, WHR, WC) were
      associated with a positive change in cognitive function. For women, a decreased
      obesity over time when obese in the baseline assessment (WHR) and an increased
      obesity over time when they had a normal adiposity in the baseline assessment
      (WC) were both associated with cognitive decline. The relationship between
      obesity and cognitive decline in the elderly is complex and some differences
      exist between the sexes. The application of the "Jolly Fat" hypothesis to
      cognitive function can only be applied to elderly men and not to elderly women.

PMID- 19108906
TI  - Percutaneous intervention of Cabrol graft-left main anastomosis during acute
      myocardial infarction.
AB  - The Cabrol technique is used to reimplant coronary arteries after aortic root
      replacement using a Dacron graft interposed between the aortic root graft and the
      native coronary artery. Although stenosis of the graft-coronary anastomosis has
      been described, there have been few reports of percutaneous intervention to these
      stenoses. An understanding of the Cabrol technique and its associated anatomical
      considerations is essential for invasive cardiologists, as they may encounter
      patients who have undergone this procedure. We report a case of emergent
      percutaneous intervention to a Cabrol graft-left main anastomosis in a patient
      who presented with acute myocardial infarction complicated by cardiogenic shock.

PMID- 19108907
TI  - Systemic blood pressure profile in hypertensive patients with low hemoglobin
      concentrations.
AB  - The purpose of the present study was to determine the relationship between anemia
      and parameters derived from 24-hour ambulatory blood pressure monitoring. We
      found that patients with anemia had significantly elevated nocturnal systolic and
      mean blood pressure and a trend for increased diastolic blood pressure. In
      addition, anemic patients had significantly lower dipping status compared to
      patients with normal hemoglobin levels.

PMID- 19108908
TI  - Impact of high-density lipoprotein cholesterol level in patients with variant
      angina pectoris.
AB  - BACKGROUND: It is generally considered that patients with variant angina pectoris
      (VAP) have a potential disturbance in the coronary endothelium. High-density
      lipoprotein (HDL) has been shown to mediate vasodilation as a result of its
      endothelium-enhancing property; however, the significance of low HDL in patients
      with VAP has not been clarified. We sought to determine the association between a
      low level of high-density lipoprotein cholesterol (HDL-C) and VAP. METHODS: We
      examined a total of 174 consecutive patients who were suspected of having VAP and
      underwent spasm provocation test by direct injection of acetylcholine into the
      coronary arteries. One hundred and three patients (59%) were consequently
      diagnosed as having VAP. Serum HDL-C, fasting plasma glucose (FPG), and
      glycohemoglobin levels were measured in all patients. RESULTS: HDL-C in quartiles
      showed a significant negative correlation with the presence of VAP. Multivariate
      analysis revealed that the lowest HDL-C quartile (<43 mg/dl), as well as
      cigarette smoking and impaired fasting glucose/diabetes mellitus, was an
      independent determinant of VAP (odds ratio=3.39, P=0.010). Patients in the
      highest FPG quartile (> or =106 mg/dl) or with cigarette smoking habit in
      combination with the lowest HDL-C quartile showed an increased risk for VAP
      (relative risk=2.01 and 1.88, respectively). CONCLUSIONS: A low level of HDL-C is
      an independent determinant for VAP. Endothelial dysfunction caused by a low HDL
      state may play a role in the development of VAP.

PMID- 19108909
TI  - Real three-dimensional assessment of left atrial and left atrial appendage
      volumes by 64-slice spiral computed tomography in individuals with or without
      cardiovascular disease.
AB  - CONTEXT: Left atrial (LA) volume is a prognosis factor of cardiovascular
      morbidity in patients with cardiovascular disease (CD). Recent developments of
      multislice computed tomography (MSCT) have made non invasive coronary angiography
      reliable for selected patients and new software facilitates truly volume
      measurements without geometrical assumptions. OBJECTIVE: To define, by using
      MSCT, LA and left atrial appendage (LAA) volumes in patients with or without CD.
      METHODS AND RESULTS: In the population of patients referred to our laboratory for
      a conventional MSCT coronary angiography, 40 individuals without CD (Normal
      group) and 80 patients with CD (CD group) were prospectively selected. The CD
      group was constituted from 4 subgroups of patients with either coronary artery
      disease (n=20), idiopathic dilated cardiomyopathy (n=20), left ventricular
      hypertrophy (n=20) or severe mitral regurgitation (MR group, n=20). LAA and LA
      volumes were measured on a commercially available workstation. LA maximal and
      minimal volumes were lower in Normal group than in CD group, as LA ejection
      fraction (54+/-10 versus 67+/-20 ml/m(2), p<0.0001; 31+/-8 versus 46+/-20
      ml/m(2), p<0.0001; 43+/-8% versus 33+/- 14%, p<0.001). LAA volume was larger in
      MR group than in Normal group (15+/-7 ml versus 9+/-3 ml, p<0.0001). CONCLUSION:
      This MSCT study provides normal values of LA and LAA volumes for patients who
      underwent MSCT coronary angiography and suggests that MSCT is helpful to assess
      the changes of LA volumes related to various CD.

PMID- 19108910
TI  - A rare congenital coronary artery anomaly: anomalous of the left anterior
      descending coronary artery arising from the right coronary artery and review of
      the literature.
AB  - Most coronary anomalies are clinically asymptomatic. However some of them may
      present with chest pain, syncope, heart failure and sudden death. Anomalous left
      anterior descending artery arising from right coronary artery is a very rare
      coronary anomaly.

PMID- 19108911
TI  - Geodesic pattern of coronary arteries as a predictor for cardiovascular risk:
      clinical perspectives.
AB  - Coronary angiography, despite current shortcomings, has been regarded as golden
      standard for the assessment of coronary arteries. Geodesic pattern of coronary
      arteries characterized by curvature, torsion and tortuosity parameters can also
      be determined through angiography. Apart from atherosclerosis; age, hypertension,
      left ventricular hypertrophy and coronary flow are some of the determinants for
      the geodesic pattern of coronary arteries. Besides, a unique feature of coronary
      vasculature that differs from all other arterial sites is the repetitive flexion
      during each cardiac contraction. Thus, the geodesic pattern of coronary arteries
      may conceivably possess an adjunctive merit in estimating cardiovascular risk and
      have promising implications for discerning those who require meticulous follow
      up. A more thorough understanding of the precise determinants for the coronary
      geodesic pattern would help establish its potential causal interaction with
      cardiovascular risk.

PMID- 19108912
TI  - Gas exchange and central hemodynamics in patients with severe heart failure.

PMID- 19108913
TI  - The association between resistin, high-density lipoprotein cholesterol and
      carotid atherosclerosis in elderly women with hypertension.

PMID- 19108914
TI  - Functional significance of the conus artery as a collateral to an occluded left
      anterior descending artery demonstrated by stress echocardiography.
AB  - Dobutamine stress echocardiography is a sensitive tool used for the detection of
      ischaemia. However, on occasion, there is a discrepancy between angiographic
      lesion severity and what would be expected from the abnormalities seen at stress
      echo. When stress echo underestimates severity it may be the case that collateral
      vessels play a significant role in preserving myocardial function. We present a
      case study where collateral flow in an occluded left anterior descending artery
      (LAD) is demonstrated as coming from the conus branch; and where stress
      echocardiography shows the relative preservation of function in the affected
      segments. Although rarely observed in clinical practice, the conus artery has
      occasionally been noted as a source of collateral blood flow. For the first time
      in the literature, this case demonstrates that the conus can provide functionally
      significant collateral blood supply to an occluded LAD.

PMID- 19108915
TI  - Effect of sleep deprivation on cardiovascular health.

PMID- 19108916
TI  - Implication of dysregulated cardiomyocyte and myocyte autophagy in the
      pathogenesis of noncompaction.

PMID- 19108917
TI  - Primary stenting in the patients with acute myocardial infarction: the preferred
      strategy.

PMID- 19108918
TI  - Coronary artery stent fracture with aneurysm formation and in-stent restenosis.
AB  - Coronary stent fracture is a relatively rare but potentially serious complication
      of coronary artery stenting. It has been recognised as a cause of in-stent
      restenosis as well as acute stent thrombosis. Most fractures occur in stents
      after aggressive post-dilatation, stents implanted in tortuous and calcified
      lesions, and after cardiac trauma [M.S. Lee, D. Jurewitz, J. Aragon, J.
      Forrester, R.R. Makkar, S. Kar Stent fracture associated with drug-eluting
      stents: clinical characteristics and implications. Catheter Cardiovasc Interv.
      Feb 15 2007;69(3):387-394.,Makaryus AN, Lefkowitz L, Lee AD, Coronary artery
      stent fracture. Int J Cardiovasc Imaging. Jun 2007;23(3):305-309. Electronic
      publication 2006 Sep 28.,E.S. Brilakis, C. Maniu, M. Wahl, G. Barsness (2004)
      Unstable angina due to stent fracture J Invasive Cardiol 16(9):545.,G. Sianos, S.
      HOfma, J.M. Ligthart et al. Stent fracture and restenosis in the drug eluting
      stent era. Catheter cardiovasc Interv 2004; 61(1):111-116.]. We report on a case
      of delayed stent fracture that gradually lead to in-stent restenosis (distal
      part), significant fragment displacement with the formation of a coronary artery
      aneurysm that was unsuitable for percutaneous intervention.

PMID- 19108919
TI  - Variations in population-based levels of C-reactive protein, cardiovascular
      morbidity and all-cause mortality: an analysis of the relationship between C
      reactive protein, Troponin-T, cardiovascular morbidity and death rates in an
      unselected population in Southwest Norway.
AB  - BACKGROUND: Large population-based studies link inflammation to the prospective
      development of cardiovascular events. We investigated the time-dependent
      associations between variations in infectious disease as reflected by alterations
      of C-reactive protein (CRP)-levels in the general population and the number of
      cardiovascular events and death rates. METHODS: Retrospectively, we studied CRP-
      and Troponin T (TNT) values drawn for any clinical reason, the number of
      cardiovascular events and the death rates in the population of Southern Rogaland,
      Norway over a 2 year period. RESULTS: The mean and the sum of CRP values per week
      were significantly correlated with the number of patients with a TNT> or =0.03
      microg/l in the same week (R=0.42, R=0.43, respectively, p<0.001 for both
      analysis). Further, we found a significant correlation between the mean and the
      sum of CRP values per week and the number of patients admitted with a
      cardiovascular event 2 weeks later (R=0.20, R=0.26; p=0.047, p=0.009,
      respectively). The sum of CRP values per week was significantly correlated to the
      death rates in the following week (R=0.30, p=0.002). CONCLUSIONS: These findings
      further support the hypothesis that inflammation assessed by CRP levels is linked
      to the prospective development of cardiovascular events and all cause mortality.

PMID- 19108920
TI  - Type B aortic dissection in a patient with unknown left ventricular non
      compaction cardiomyopathy: cardiovascular magnetic resonance diagnosis.
AB  - A 61-year-old man was referred at our hospital for a cardiac evaluation after an
      episode of oppressive chest pain at rest. He was discharged with a MRI diagnosis
      of non-compaction cardiomyopathy presented with typical angina, left ventricle
      dysfunction and ischemic EKG findings without atherosclerotic narrowing and also
      with a type B aortic dissection, documented also by computed tomography.

PMID- 19108921
TI  - Physical activity may promote sleep in cardiac patients suffering from insomnia.
AB  - Data obtained from a national household survey in Greece (n=1005) were used to
      assess the relationship between physical activity and insomnia in a group of
      subjects suffering from several major disabling physical illnesses. A self
      administered questionnaire with questions pertaining to general health and
      related issues was given to the participants. The Short Form-36, the Athens
      Insomnia Scale (AIS), and the International Physical Activity Questionnaire
      (IPAQ) were included in the assessment. Half (49.5%) of the participants had
      moderate or vigorous physical activity and 33.4% had a chronic somatic disease.
      The prevalence of insomnia in the total sample was 25.3% (n=254); subjects having
      moderate or vigorous physical activity were 56% less likely to have insomnia in
      univariate analysis. Multiple analysis revealed a significant interaction of
      physical activity with heart failure or myocardial ischemia (OR=0.054, 95% CI:
      0.003-0.95), indicating that subjects having moderate or vigorous physical
      activity and heart failure or myocardial ischemia had lower odds for having
      insomnia compared to individuals with heart problems and low physical activity
      levels. Consequently, cardiac patients suffering from insomnia seem to benefit
      from physical exercise. Since sleep disorders are quite frequent in cardiac
      patients and may result in both physical and psychological complications which
      deteriorate even further their quality of life and health, our results need
      replication in this particularly vulnerable population.

PMID- 19108922
TI  - Managed care's price bargaining with hospitals.
AB  - Research has shown that managed care (MC) slowed the rate of growth in health
      care spending in the 1990s, primarily via lower unit prices paid. However, the
      mechanism of MC's price bargaining has not been well studied. This article uses a
      unique panel dataset with actual hospital prices in Massachusetts between 1994
      and 2000 to examine the sources of MC's bargaining power. I find two significant
      determinants of price discounts. First, plans with large memberships are able to
      extract volume discounts across hospitals. Second, health plans that are more
      successful at channeling patients can extract greater discounts. Patient
      channeling can add to the volume discount that plans negotiate.

PMID- 19108923
TI  - Enterococci from artisanal dairy products show high levels of adaptability.
AB  - Enterococci are ubiquitous organisms able to promote both health (fermented
      food/probiotics) and illness (human/animal infections). Disturbingly, several
      enterococcal species commonly found in artisanal cheeses, such as Enterococcus
      faecalis and E. faecium, are being increasingly established as causes of
      infection, posing a problem for food safety. In this study enterococci from ewe's
      milk and cheese were compared to clinical and reference strains by growth in
      media simulating environmental colonization and infection sites: 2YT, BHI, skim
      milk, urine and rabbit serum at different pHs, NaCl concentrations and
      temperatures. Growth curves were obtained with Microbiology Workstation Bioscreen
      C and used to calculate relative indexes--RIs--(based on absorbance, lag phase
      and specific growth rate) for each strain and environmental condition. Similar or
      higher RIs were obtained for food strains growing in infection-related
      environments when compared to clinical ones, revealing their ability to adapt and
      grow in these conditions. A dendrogram built using Pearson's correlation
      coefficient and a PCA analysis clustered the strains regardless of their origin
      or species allocation, suggesting a strain-specific mode of growth and a high
      environmental adaptability of enterococcal strains. These evidences turn
      essential the evaluation of strains to be used as starters or probiotics.

PMID- 19108924
TI  - Disseminated Mycobacterium marinum infection in a patient with diabetic
      nephropathy.

PMID- 19108925
TI  - Immediate and long-term effects of glucomannan on total ghrelin and leptin in
      type 2 diabetes mellitus.
AB  - Effects of glucomannan as a supplementary treatment in type 2 diabetes mellitus
      were investigated by measuring ghrelin, leptin and insulin responses to OGTT.
      Glucomannan enhanced prandial ghrelin reduction when given before glucose load
      and impeded the rise of fasting ghrelin after 4-week supplement. Ghrelin-induced
      feeding may be attenuated by glucomannan.

PMID- 19108926
TI  - Relationship between activated partial thromboplastin time, heparin and potassium
      levels.

PMID- 19108927
TI  - Comparison of pre- versus post-meal administration of voglibose in men with or
      without impaired glucose tolerance.

PMID- 19108928
TI  - Four-fold increase in foot ulcers in type 2 diabetic subjects without an increase
      in major amputations by a multidisciplinary setting.
AB  - AIMS: We observed a large increase in type 2 diabetic subjects with foot ulcers
      in our diabetic outpatient foot clinic and wanted to identify the amputations
      rate and individuals at risk of amputations by comparing those who had had a
      regular control in the multidisciplinary foot clinic prior to the amputations and
      those who had not. METHODS: We examined all clinical records from the orthopaedic
      surgery department and the diabetic outpatient foot clinic of diabetic patients
      who underwent amputations for 6 years. RESULTS: Eighty-eight patients with type 2
      diabetes underwent 142 amputations; 42 major and 100 minor amputations. There was
      no increase in the number of major amputations in this period. In the group not
      followed in the foot clinic prior to amputations we showed a greater major
      amputations rate (p<0.05), although this group had a shorter duration of diabetes
      and less retinopathy, nephropathy and AMI/stroke. Everyone in both groups had
      severe neuropathy and ischemia. CONCLUSION: A multidisciplinary diabetic foot
      clinic may decrease the risk of major amputations in type 2 diabetic subjects
      with foot ulcers. Severe neuropathy and ischemia were the most important risk
      factors.

PMID- 19108929
TI  - The core determinants of health expenditure in the African context: some
      econometric evidence for policy.
AB  - This paper, using cross-sectional data from 44 (83% of all) African countries for
      year 2001, presents econometric model estimates linking real per-capita health
      expenditure (HEXP) to a host of economic and non-economic factors. The empirical
      results of OLS and robust LAE estimators indicate that real per-capita GDP
      (PRGDP) and real per-capita foreign aid (FAID) resources are both core and
      statistically significant correlates of HEXP. Our empirical results suggest that
      health care in the African context is technically, a necessity rather than a
      luxury good (for the OECD countries). This suggests that the goal of health
      system in Africa is primarily 'physiological' or 'curative' rather than 'caring'
      or 'pampering'. The positive association of HEXP with FAID hints that external
      resource inflows targeting health could be instrumental for spurring economic
      progress in good policy environments. Most African countries until the late 1990s
      experienced economic and political instability, and faced stringent structural
      adjustment mandates of the major international financial institution lenders for
      economic development. Therefore, our finding a positive effect of FAID on HEXP
      could suggest that external resource inflows softened some of the macroeconomic
      fiscal deficit impacts on HEXP in the 2000s. Policy implications of country
      specific elasticity estimates are given.

PMID- 19108931
TI  - Irradiance regulates genotype-specific responses of Rhizobium-nodulated soybean
      to increasing iron and two manganese concentrations in solution culture.
AB  - The growth of soybean plants were examined when subjected to three contrasting
      irradiance levels and to various combinations of nutrient solution Fe and Mn
      concentrations. Two Rhizobium-nodulated soybean genotypes (PI 227557 and Biloxi),
      which had been previously found to differ in their growth response to various Fe
      and Mn solutions, were studied. Both genotypes displayed the poorest growth,
      nodulation and the lowest chlorophyll and nodule ureide concentration at high
      irradiance (HI), regardless of the solution Fe and Mn concentrations. However,
      the genotypes differed under HI in their accumulation of Fe. For solution
      concentrations greater than 13 microM, PI 227557 accumulated up to 1200 microg
      Feg(-1) leaf dry wt mainly in the form of ferritin crystals within chloroplasts.
      In contrast, leaf Fe concentrations in Biloxi only reached 300 microg Feg(-1) dry
      wt and there were no ferritin crystals. Also, in PI 227557 HI induced more severe
      distortions in leaf cells and nodule ultrastructure than in Biloxi. Based on its
      poor growth under HI, PI 227557 could be categorized as an Fe-inefficient
      genotype prone to undergo photoinhibition at HI, in spite of the ferritin
      crystals in the chloroplasts. Enhanced growth, nodulation, chlorophyll and ureide
      concentrations in nodules as well as leaf ureide catabolism occurred in both
      genotypes grown at moderate irradiance (MI) in Fe solutions from 13 to 60 microM
      supplied with 20 microM Mn. At low irradiance (LI), plant growth and nodulation
      were lower than at MI values, but higher than those of plants at HI. Irradiance
      and solution Fe concentration did not alter leaf Cu and Zn concentration in
      either genotype, with the higher concentrations of these two elements detected in
      Biloxi. Solutions with Fe concentrations greater than 100 microM were deleterious
      for both genotypes at all irradiances. Low Fe and high Mn concentrations in
      leaves was bound to result in the best growth at HI.

PMID- 19108930
TI  - Evolutionary mutant models for human disease.
AB  - Although induced mutations in traditional laboratory animals have been valuable
      as models for human diseases, they have some important limitations. Here, we
      propose a complementary approach to discover genes and mechanisms that might
      contribute to human disorders: the analysis of evolutionary mutant models in
      which adaptive phenotypes mimic maladaptive human diseases. If the type and mode
      of action of mutations favored by natural selection in wild populations are
      similar to those that contribute to human diseases, then studies in evolutionary
      mutant models have the potential to identify novel genetic factors and gene-by
      environment interactions that affect human health and underlie human disease.

PMID- 19108932
TI  - Interventional evaluation of environmental contamination by vancomycin-resistant
      enterococci: failure of personnel, product, or procedure?
AB  - It is not clear whether improvement in environmental decontamination is more
      efficiently achieved through changes in cleaning products, cleaning procedures,
      or performance of cleaning personnel. To assess the impact of cleaning
      performance on environmental contamination with vancomycin-resistant enterococci
      (VRE), we conducted a sequential trial in which a multifaceted environmental
      cleaning improvement intervention was introduced in a medical intensive care unit
      and respiratory step-down unit. The intervention included educational lectures
      for housekeepers and an observational programme of their activities without
      changes in cleaning products or written procedures. Following these
      interventions, the proportion of environmental sites cleaned improved from 49% to
      85% (P<0.001); contamination of environmental sites declined from 21% to 8%
      (P<0.0001) before cleaning and from 13% to 8% (P<0.0001) after cleaning. The
      improved cleaning and contamination rates persisted in a washout period. In a
      multivariate model, cleaning thoroughness strongly influenced the degree of
      environmental contamination, with a 6% decline in VRE prevalence with every 10%
      increase in percentage of sites cleaned. These findings suggest that surface
      contamination with VRE is due to a failure to clean rather than to a faulty
      cleaning procedure or product.

PMID- 19108933
TI  - Spread of bacteria on surfaces when cleaning with microfibre cloths.
AB  - The impact of environmental contamination on nosocomial cross-transmission is
      mostly unresolved and in Danish hospitals assessment of cleaning is based on
      visible criteria only. The use of premoistened microfibre cloths and the 16-side
      method have been introduced into Danish hospitals because of economic and
      ergonomic advantages but they have not been evaluated for applicability in
      hospital cleaning. Our hypothesis was that this method may spread bacteria. A
      surface was contaminated with bacteria (4 cfu/bacteria/cm(2)), and cleaned with a
      premoistened microfibre cloth folded to 16-side use. Each of 15 sterile surfaces
      was cleaned with a new side of the microfibre cloth; imprints were made and the
      experiment repeated 12 times. After cleaning, the contaminated surface imprints
      of microfibre cloths showed a median of 45.5 cfu/plate for E. faecalis and 2.5
      cfu/plate for B. cereus. Median values from imprints from cloth sides 2-16 were
      between 1 and 12 cfu/plate for E. faecalis and 0 cfu/plate for B. cereus.
      Imprints of the contaminated surfaces were a median of 45.5 cfu/plate for E.
      faecalis, giving a reduction of 5.6-fold. For B. cereus the median value was 0
      cfu/plate. The surface numbers 2-16 had median values between 0.5 and 7.5 for E.
      faecalis, which was spread to 11-15 of the 15 sterile surfaces (P<0.01). B.
      cereus was found in six out of 180 imprints on surfaces 2-16, all with 1
      cfu/plate (non-significant). The implication is that although there was an
      overall reduction in bacterial counts on the contaminated surface, bacteria were
      spread to subsequently cleaned surfaces.

PMID- 19108935
TI  - Teaching during clinical practice: strategies and techniques used by preceptors
      in nursing education.
AB  - The preceptor is a nurse who teaches and supports the student and is seen as
      pivotal to student learning within the clinical setting. Earlier studies have
      shown that preceptors' pedagogical competence is significant for facilitating
      learning during clinical practice. However, studies describing pedagogical
      competence, especially in terms of teaching strategies, seem to be scarce. The
      aim of this study was to describe which strategies and techniques preceptors use
      to teach undergraduate nursing students during clinical practice. The study had
      an ethnographic approach; methods used were participant observations and focus
      group interviews with nurses who were experienced in precepting undergraduate
      nursing students. Findings illustrated how preceptors used different strategies
      and techniques in a continuous process of adjusting, performing and evaluating
      precepting. Increased knowledge on how the preceptors actually teach student
      nurses during clinical practice will help facilitate educational programmes for
      preceptors, which will enhance their pedagogical skills and competences.

PMID- 19108934
TI  - Amyloid-beta protein impairs Ca2+ release and contractility in skeletal muscle.
AB  - Inclusion body myositis (IBM), the most common muscle disorder in the elderly, is
      partly characterized by dysregulation of beta-amyloid precursor protein (betaAPP)
      expression and abnormal, intracellular accumulation of full-length betaAPP and
      beta-amyloid epitopes. The present study examined the effects of beta-amyloid
      accumulation on force generation and Ca(2+) release in skeletal muscle from
      transgenic mice harboring human betaAPP and assessed the consequence of Abeta(1
      42) modulation of the ryanodine receptor Ca(2+) release channels (RyRs). beta
      Amyloid laden muscle produced less peak force and exhibited Ca(2+) transients
      with smaller amplitude. To determine whether modification of RyRs by beta-amyloid
      underlie the effects observed in muscle, in vitro Ca(2+) release assays and RyR
      reconstituted in planar lipid bilayer experiments were conducted in the presence
      of Abeta(1-42). Application of Abeta(1-42) to RyRs in bilayers resulted in an
      increased channel open probability and changes in gating kinetics, while addition
      of Abeta(1-42) to the rabbit SR vesicles resulted in RyR-mediated Ca(2+) release.
      These data may relate altered betaAPP metabolism in IBM to reductions in RyR
      mediated Ca(2+) release and muscle contractility.

PMID- 19108936
TI  - Research governance: Has it become a research hindrance?

PMID- 19108937
TI  - Butyrate modulates oxidative stress in the colonic mucosa of healthy humans.
AB  - BACKGROUND & AIMS: Butyrate, a short-chain fatty acid produced by colonic
      microbial fermentation of undigested carbohydrates, has been implicated in the
      maintenance of colonic health. This study evaluates whether butyrate plays a role
      in oxidative stress in the healthy colonic mucosa. METHODS: A randomized, double
      blind, cross-over study with 16 healthy volunteers was performed. Treatments
      consisted of daily rectal administration of a 60 ml enema containing 100 mM
      sodium butyrate or saline for 2 weeks. After each treatment, a blood sample was
      taken and mucosal biopsies were obtained from the sigmoid colon. In biopsies, the
      trolox equivalent antioxidant capacity, activity of glutathione-S-transferase,
      concentration of uric acid, glutathione (GSH), glutathione disulfide and
      malondialdehyde, and expression of genes involved in GSH and uric acid metabolism
      was determined. Secondary outcome parameters were CRP, calprotectin and
      intestinal fatty acid binding protein in plasma and histological inflammatory
      scores. RESULTS: Butyrate treatment resulted in significantly higher GSH (p<0.05)
      and lower uric acid (p<0.01) concentrations compared to placebo. Changes in GSH
      and uric acid were accompanied by increased and decreased expression,
      respectively, of their rate limiting enzymes determined by RT-PCR. No significant
      differences were found in other parameters. CONCLUSIONS: This study demonstrated
      that butyrate is able to beneficially affect oxidative stress in the healthy
      human colon.

PMID- 19108938
TI  - Group antenatal care: new pedagogic method for antenatal care--a pilot study.
AB  - OBJECTIVE: to investigate how women who attended group antenatal care experienced
      the information they received, compared with women who attended traditional
      antenatal care, and their satisfaction with the form of care. The aim was also to
      determine the effect of group antenatal care on women's social networks compared
      with traditional antenatal care. DESIGN AND SETTING: a pilot study with an
      intervention group (group antenatal care) and a control group (traditional
      antenatal care). Both groups were selected through informed choice. A
      questionnaire and a follow-up telephone call, using a structured questionnaire,
      were used to evaluate both groups. PARTICIPANTS: for each woman who had chosen to
      be in the intervention group, two women who had chosen traditional antenatal care
      were selected from the same antenatal clinic and given the same questionnaire.
      FINDINGS: 35/45 (77%) women in the intervention group returned a completed
      questionnaire, compared with 40/85 (48%) women in the control group. There was
      little difference in satisfaction with information between the two groups, and
      overall satisfaction was high. KEY CONCLUSIONS: at six months post partum, the
      women who attended group antenatal care still met others from the group more
      regularly than the women who attended traditional antenatal care. IMPLICATIONS
      FOR PRACTICE: group antenatal care is well accepted by women, and can better
      utilise midwives' time.

PMID- 19108939
TI  - Bioaugmentation of a 4-chloronitrobenzene contaminated soil with Pseudomonas
      putida ZWL73.
AB  - The strain Pseudomonas putida ZWL73, which metabolizes 4-chloronitrobenzene
      (4CNB) by a partial-reductive pathway, was inoculated into lab-scale 4CNB
      contaminated soil for bioaugmentation purposes in this study. The degradation of
      4CNB was clearly stimulated, as indicated with the gradual accumulation of
      ammonium and chloride. Simultaneously, the diversity and quantity of cultivable
      heterotrophic bacteria decreased due to 4CNB contamination, while the quantity of
      4CNB-resistant bacteria increased. During the bioaugmentation, denaturing
      gradient gel electrophoresis analysis showed the changes of diversity in dominant
      populations of intrinsic soil microbiota. The results showed that
      Alphaproteobacteria and Betaproteobacteria were not distinctly affected, but
      Actinobacteria were apparently stimulated. In addition, an interesting dynamic
      within Acidobacteria was observed, as well as an influence on ammonia-oxidizing
      bacteria population. These combined findings demonstrate that the removal of 4CNB
      in soils by inoculating strain ZWL73 is feasible, and that specific populations
      in soils rapidly changed in response to 4CNB contamination and subsequent
      bioaugmentation.

PMID- 19108940
TI  - Unravelling the extent of inequalities in health across urban and rural areas:
      evidence from a national sample in England.
AB  - Studies of inequalities in health between rural and urban settings have produced
      mixed and sometimes conflicting results, depending on the national setting of the
      study, the level of geographic detail used to define rural areas and the health
      indicators studied. By focusing on morbidity data from a national sample of
      individuals, this study aims to examine the extent of inequalities in health
      between urban and rural areas, as well as inequalities in health across rural
      areas of England. Multilevel analyses for poor self-rated health, overweight and
      obesity, and common mental disorders are reported for a sample of 30,776
      individuals aged 18 years and older (obtained from the Health Survey for England
      years 2000-2003 combined) and distributed across 3645 small areas classed in four
      categories: two groups of urban areas (Greater London area or 'other cities') and
      two types of rural settings (semi-rural areas or villages). Results show that
      rural dwellers were significantly less likely than residents of urban areas to
      report their health as being fair or poor and to report common mental disorders,
      independent of their socio-demographic characteristics. However, as for urban
      settlements, there were significant variations in health across semi-rural areas
      and across villages, indicating the presence of health inequalities within rural
      settings in England. These inequalities were not fully explained by the
      individual composition of the areas or by the available measures of area
      socioeconomic conditions, indicating that in rural contexts more specific factors
      may have significance for health. Different policies and services for health
      promotion and care may need to be targeted to different types of rural areas.

PMID- 19108941
TI  - Quantification of monomer elution and carbon-carbon double bonds in dental
      adhesive systems using HPLC and micro-Raman spectroscopy.
AB  - OBJECTIVES: To quantify monomer elution from different adhesive systems using
      reverse-phase high-performance liquid chromatography (HPLC) and correlate this
      elution with the ratio of carbon-carbon double bonds from monomer to polymer
      (RDB) obtained using micro-Raman spectroscopy. METHODS: Thirty dentine discs were
      cut from 30 human, intact, third molars and randomly allocated to five groups
      according to the adhesive applied: total-etch, Excite (Ivoclar Vivadent), two
      bottle self-etch, Clearfil SE (Kuraray), one-bottle self-etch, Clearfil 3S
      (Kuraray), ormocer-based, Admira (Voco) and Filtek Silorane adhesive system (FS)
      (3M ESPE). Monomer elution was studied 1h, 6h, 24h, 96h and 7 days after
      immersion in 75% ethanol/water. The RDB was calculated immediately after light
      curing and thereafter at 24h and 7 days. The data were statistically analysed
      using one-way ANOVA and Pearson's correlation coefficient (p<0.05). RESULTS: More
      than 90% of the whole elution occurred during the first 1h, except for BisGMA in
      FS, with the highest absolute amount from Clearfil SE and the highest wt% from
      Admira. Initial RDB was in the ascending order FS<Admira<Excite<Clearfil
      SE<Clearfil 3S. In all groups, the RDB was significantly higher after 24h and 7
      days than immediately after light-curing (p<0.05). Negative correlation was found
      only for the elution of HEMA and the RDB of Clearfil 3S. CONCLUSIONS: Different
      adhesive systems showed different monomer elution kinetics. In all systems, the
      RDB increased after monomer elution. Overall, no direct correlation exists
      between the RDB of adhesives and the elution of unreacted monomers.

PMID- 19108942
TI  - Effect of home bleaching systems on enamel nanohardness and elastic modulus.
AB  - OBJECTIVES: The purpose of this study was to evaluate the nanohardness and
      elastic modulus of human enamel after treatment with tray and strip bleaching
      systems. METHODS: Fifty-five human enamel samples were exposed to five different
      bleaching agents. Nanoindentations were made before and after bleaching
      treatments following the manufacturer's directions using a Nanoindenter XP (MTS
      Systems Corporation, Oak Ridge, TN, USA). Nanohardness and elastic modulus
      measurements were obtained and the results were statistically analyzed using a
      repeated measures analysis of variance with a post-hoc Tukey-Kramer multiple
      comparison test. RESULTS: Nanohardness and elastic modulus measurements showed
      decrease of mean values for each group except the control which remained the
      same. There were significant differences due to time (before and after treatment)
      and material effects in nanohardness (P<0.0001) and elastic modulus (P=0.0241).
      Measurements after treatment showed significant decrease in nanohardness between
      all groups and the control group. There was a significant difference in hardness
      between CP and TO after treatment. Additionally, there were significant
      differences in elastic modulus between the control group when compared to OB and
      TO after treatment. While there were significant changes in the elastic modulus
      due to treatment for both CP and TO, there were no significant differences
      between any of the groups after treatment. CONCLUSIONS: Nanohardness and elastic
      modulus of human enamel were significantly decreased after the application of
      home-bleaching systems.

PMID- 19108943
TI  - Association of extracellular superoxide dismutase (SOD3) Ala40Thr gene
      polymorphism with pre-eclampsia complicated by severe fetal growth restriction.
AB  - OBJECTIVE: Placental and systemic oxidative stress with an imbalance in the
      oxidant/antioxidant activity seems to play a central role in the pathogenesis of
      pre-eclampsia. The aim of our study was to examine whether two missense
      polymorphisms of the extracellular superoxide dismutase (SOD3) gene (Arg213Gly
      and Ala40Thr) are associated with pre-eclampsia in a Caucasian population from
      Hungary. STUDY DESIGN: One hundred and fifty-nine pre-eclamptic patients and 114
      normotensive, healthy pregnant women were involved in this case-control study.
      The SOD3 Arg213Gly and Ala40Thr genotypes were determined using the polymerase
      chain reaction-restriction length polymorphism (PCR-RFLP) and allele-specific
      amplification methods. RESULTS: The Arg213Gly variant was not detected in our
      population. There were no significant differences in the genotype and allele
      frequencies of the SOD3 Ala40Thr polymorphism between pre-eclamptic patients and
      control subjects. However, the mutant allele carriers of this polymorphism showed
      an increased risk for severe fetal growth restriction-complicated pre-eclampsia,
      which was independent of maternal age, prepregnancy BMI, primiparity and smoking
      status (OR: 6.07, 95% CI: 1.33-27.8, p=0.020; adjusted OR: 4.89, 95% CI: 1.03
      23.2, p=0.046). CONCLUSION: Our results suggest a role of SOD3 Ala40Thr single
      nucleotide polymorphism in the risk of severe fetal growth restriction
      complicated pre-eclampsia. However, further studies are needed with a larger
      sample size to confirm our findings and to explore the exact molecular basis of
      this observation.

PMID- 19108944
TI  - Beyond BAT: selecting optimal combinations of available techniques, with an
      example from the limestone industry.
AB  - Technological choices are multi-dimensional and thus one needs a multi
      dimensional methodology to identify best available techniques. Moreover, in the
      presence of environmental externalities generated by productive activities,
      'best' available techniques should be best from Society's point of view, not only
      in terms of private interests. In this paper we present a modeling framework
      based on methodologies appropriate to serve these two purposes, namely linear
      programming and internalization of external costs. We develop it as an
      operational decision tool, of interest for both firms and regulators, and we
      apply it to a plant in the lime industry. We show why, in this context, there is
      in general not a single best available technique (BAT), but well a best
      combination of available techniques to be used (BCAT).

PMID- 19108945
TI  - Laser therapy for upper urinary tract transitional cell carcinoma: indications
      and management.
AB  - CONTEXT: Ureteroscopically guided laser techniques are commonly used in the
      treatment of upper urinary tract transitional cell carcinoma (UUTT); however,
      there is an ongoing debate with regard to indication and management. OBJECTIVE:
      To review the indication, feasibility, and treatment outcome of laser application
      for definitive endoscopic treatment of UUTT, focusing on technical aspects of
      different laser devices and their impact on tissue. EVIDENCE ACQUISITION: PubMed
      and Medline were searched for reports on laser therapy in UUTT from 1980 to 2008,
      with particular focus on the technical background of various laser systems.
      EVIDENCE SYNTHESIS: For decades, nephroureterectomy has been considered the gold
      standard for treating UUTT. With the intent to preserve functioning renal
      parenchyma, minimally invasive approaches, initially advocated for patients
      requiring a nephron-sparing approach (ie, single functioning kidney, renal
      insufficiency or significant comorbidities), have gained widespread acceptance
      due to advances in ureteroscopy, percutaneous renal surgery, and laparoscopy.
      Ureteroscopically guided laser ablation has been used successfully, resulting in
      recurrence rates ranging from 31% to 65% and disease-free rates of 35% to 86%,
      depending on stage and grade at diagnosis. CONCLUSIONS: To obtain the highest
      treatment success, the initial staging and grading of the tumour is crucial.
      Because low-grade tumours rarely if ever progress in stage or grade, the success
      rate of ureteroscopic therapy parallels that of endoscopic resection of identical
      bladder tumours. In the treatment of higher grade, advanced tumours,
      ureteroscopic therapy is less likely to be curative, and thus, endoscopic
      manoeuvres can only be palliative. Due to the relatively low prevalence of this
      tumour and the lack of comparable randomised, multicentre trials, the indications
      for an endoscopic laser treatment option has to be defined based on the patient's
      individual situation.

PMID- 19108947
TI  - High concentrations of ascorbic acid induces apoptosis of human gastric cancer
      cell by p38-MAP kinase-dependent up-regulation of transferrin receptor.
AB  - We investigated the molecular mechanism by which ascorbic acid (AA) induces
      apoptosis in human gastric cancer cells, AGS cells. High concentration (more than
      5mM) of AA increased cellular iron uptake by increasing transferrin receptor
      (TfR) expression and induced AGS cell apoptosis which was inhibited by catalase.
      Interestingly, p38 mitogen-activated protein kinase (MAPK) inhibitor inhibited
      the upregulation of TfR and increased cell survival by AA. TfR-siRNA-transfected
      cells reduced apoptosis by AA. H(2)O(2) increased TfR expression in AGS cells.
      Taken together, we concluded that high concentration of AA, through H(2)O(2),
      induces apoptosis of AGS cells by p38-MAPK-dependent upregulation of TfR.

PMID- 19108948
TI  - Apoptosis induced by 2-acetyl-3-(6-methoxybenzothiazo)-2-yl-amino-acrylonitrile
      in human leukemia cells involves ROS-mitochondrial mediated death signaling and
      activation of p38 MAPK.
AB  - Benzothiazoles are multitarget agents with broad spectrum of biological activity.
      2-Acetyl-3-(6-methoxybenzothiazo)-2-yl-amino-acrylonitrile (AMBAN) is a new
      synthetically prepared derivative, which in our previous study showed cytotoxic
      effects towards tumor cells. The aim of the present study was to examine the
      antiproliferative and apoptosis inducing activities of AMBAN towards human
      leukemia HL60 and U937 cells. Further, the molecular mechanism involved in AMBAN
      induced apoptosis was investigated. Benzothiazole inhibited the growth and
      induced programmed cell death of HL60 and U937 cells. In addition, AMBAN elevated
      the level of reactive oxygen species, decreased the mitochondrial membrane
      potential, activated caspases 9 and 3, induced the cytochrome c release and PARP
      cleavage and led to intranucleosomal DNA fragmentation. Further, p38 MAPK was
      associated with the apoptotic activity of AMBAN. It can be concluded that AMBAN
      induced apoptosis in HL60 and U937 cells through mitochondrial/caspase 9/caspase
      3-dependent pathway.

PMID- 19108949
TI  - BO-0742, a derivative of AHMA and N-mustard, has selective toxicity to drug
      sensitive and drug resistant leukemia cells and solid tumors.
AB  - This is a preclinical study of BO-0742, a derivative of 3-(9-acridinylamino)-5
      hydroxymethyl-aniline (AHMA) and N-mustard, as an anti-cancer agent. MTS assays
      revealed a broad spectrum of anti-cancer activities in vitro, with the greatest
      cytotoxicity against leukemia and neuroblastoma including those with drug
      resistant characteristics, and a good therapeutic index with leukemia being 10-40
      times more sensitive to BO-0742 than hematopoietic progenitors. Administration of
      BO-0742 at an optimal dose schedule based on its pharmacokinetics significantly
      suppressed the growth of xenografts of human breast and ovarian cancers in mice.
      Thus, BO-0742 is a potent anti-cancer agent worthy of further clinical
      development.

PMID- 19108950
TI  - SOX7, down-regulated in colorectal cancer, induces apoptosis and inhibits
      proliferation of colorectal cancer cells.
AB  - The sex-determining region Y-box 7 (Sox7) is a member of high mobility group
      (HMG) transcription factor family, essential for embryonic development and
      endoderm differentiation. Deregulation of Wnt signaling pathway is a hallmark of
      colorectal cancer. Our results showed that the expression level of SOX7 was
      frequently down-regulated in human colorectal cancer cell lines and in primary
      colorectal tumor tissues, and the SOX7 silencing was partially due to the
      aberrant DNA methylation of the gene. Restoration of SOX7 induced colorectal
      cancer cell apoptosis, inhibited cell proliferation and colony formation. In
      addition, SOX7 efficiently suppressed beta-catenin-mediated transcriptional
      activity.

PMID- 19108952
TI  - Joint degeneration and chronic pain: still looking for the missing link.

PMID- 19108951
TI  - Evaluating the effectiveness of exposure and acceptance strategies to improve
      functioning and quality of life in longstanding pediatric pain--a randomized
      controlled trial.
AB  - Although several studies have illustrated the effectiveness of cognitive behavior
      therapy (CBT) on adult pain patients, there are few randomized controlled trials
      on children and adolescents. There is particularly a need for studies on
      pediatric patients who are severely disabled by longstanding pain syndromes.
      Acceptance and Commitment Therapy, as an extension of traditional CBT, focuses on
      improving functioning and quality of life by increasing the patient's ability to
      act effectively in concordance with personal values also in the presence of pain
      and distress. Following a pilot study, we sought to evaluate the effectiveness of
      an ACT-oriented intervention based on exposure and acceptance strategies and to
      compare this with a multidisciplinary treatment approach including amitriptyline
      (n=32). The ACT condition underwent a relatively brief treatment protocol of
      approximately 10 weekly sessions. Assessments were made before and immediately
      after treatment, as well as at 3.5 and 6.5 months follow-up. Prolonged treatment
      in the MDT group complicated comparisons between groups at follow-up assessments.
      Results showed substantial and sustained improvements for the ACT group. When
      follow-up assessments were included, ACT performed significantly better than MDT
      on perceived functional ability in relation to pain, pain intensity and to pain
      related discomfort (intent-to-treat analyses). At post-treatment, significant
      differences in favor of the ACT condition were also seen in fear of re/injury or
      kinesiophobia, pain interference and in quality of life. Thus, results from the
      present study support previous findings and suggest the effectiveness of this ACT
      oriented intervention for pediatric longstanding pain syndromes.

PMID- 19108953
TI  - Growth and field emission properties of ZnO nanostructures deposited by a novel
      pulsed laser ablation source on silicon substrates.
AB  - Zinc oxide (ZnO) nanostructures were produced using a novel pulsed laser ablation
      apparatus comprising in-situ analysis of the plume by reflection time-of-flight
      mass spectrometry. Various morphologies of nano and microstructures were obtained
      for laser wavelengths of 1064 and 355nm, and oxygen ambient pressures of 10(-6)
      and 10(-2)mbar, respectively. None of the produced structures exhibited a
      particular type of self-organisation whereas all of them showed low aspect ratios
      and good field emission properties. Optimum values of 5.2Vmicrom(-1) and 2060
      were obtained for the turn-on field and Fowler-Nordheim enhancement factor,
      respectively, for deposited nano-tipped microstructures presenting a high
      coverage of the substrate. The experimental data showed that for a given laser
      wavelength, higher field enhancement factors were obtained for the samples grown
      at the lower pressure of 10(-6)mbar. In these conditions, the deposited materials
      showed distinct nanostructuring and comparison with existing data showed the
      corresponding ablation plumes to contain (ZnO)(n) clusters, up to n=13. This work
      also shows that the electronic properties of the nanostructured ZnO produced in
      our conditions, as determined by the oxygen concentration during deposition, have
      an influence on the field emission properties in addition to the nanostructure
      morphology.

PMID- 19108954
TI  - Characterization of local immune response against lungworms in naturally infected
      sheep.
AB  - This study describes the immunohistochemical and histochemical phenotypes of
      inflammatory cells in sheep lungs infected with lungworms. A total of 20
      naturally infected sheep lungs were used. Protostrongylus spp., Muellerius
      capillaris, Neostrongylus linearis, and Cystocaulus ocreatus were the chief
      organisms determined from such lesions, which were of a chronic nature. All the
      lungs had many developmental stages of the parasites and a similar inflammatory
      response, which included numerous mast cells, eosinophils, T cells, B cells,
      dendritic cells, and macrophages. In the bronchial and interstitial tissues, the
      inflammatory cells were dominated by MHCII, CD1, CD4, CD5, CD14, CD21, IgM, and
      CD172a positive cells, whereas CD2 and WC1 positive cells were detected less. The
      data provided additional evidence that subsets of inflammatory cells were
      included within ovine lungs infected with lungworms; however, understanding the
      entire immune-response process and development of resistance to lungworms in
      sheep remain to be clearly elucidated.

PMID- 19108955
TI  - Trichinella diagnostics and control: mandatory and best practices for ensuring
      food safety.
AB  - Because of its role in human disease, there are increasing global requirements
      for reliable diagnostic and control methods for Trichinella in food animals to
      ensure meat safety and to facilitate trade. Consequently, there is a need for
      standardization of methods, programs, and best practices used in the control of
      Trichinella and trichinellosis. This review article describes the biology and
      epidemiology of Trichinella, and describes recommended test methods as well as
      modified and optimized procedures that are used in meat inspection programs. The
      use of ELISA for monitoring animals for infection in various porcine and equine
      pre- and post-slaughter programs, including farm or herd certification programs
      is also discussed. A brief review of the effectiveness of meat processing
      methods, such as freezing, cooking and preserving is provided. The importance of
      proper quality assurance and its application in all aspects of a Trichinella
      diagnostic system is emphasized. It includes the use of international quality
      standards, test validation and standardization, critical control points,
      laboratory accreditation, certification of analysts and proficiency testing. Also
      described, are the roles and locations of international and regional reference
      laboratories for trichinellosis where expert advice and support on research and
      diagnostics are available.

PMID- 19108956
TI  - The effects of alcohol and cue salience on young men's acceptance of sexual
      aggression.
AB  - Research suggests that alcohol intoxication may increase a young man's likelihood
      of sexual aggression. This laboratory analogue experiment tested a disinhibition
      versus alcohol myopia explanation of alcohol's role by investigating effects of
      acute alcohol administration, expectations and individual differences drawn from
      Malamuth's Confluence Model of Sexual Aggression (i.e., Acceptance of
      Interpersonal Violence: AIV, Need for Sexual Dominance: NSD) on young men's
      acceptance of sexual aggression. Young adult heterosexual men (n=334) attended
      two laboratory sessions each. In the first, they completed screening and
      individual differences measures. In the second, they were assigned randomly to
      consume one of four beverages: Control, Placebo, Low Dose Alcohol (0.33 ml
      alcohol/kg body weight) or Moderate Dose Alcohol (0.75 ml/kg) and view one of two
      video-delivered scenario conditions: "Anti-Force Cues" (scenario of a couple on a
      date with embedded explicit cues mitigating against forced sex) or "No Cues"
      (Identical scenario with no Anti-Force cues). Participants then judged 1) should
      the man continue to force the woman to have sex? 2) would they force the woman?
      and 3) who was responsible for the outcome? Results supported a disinhibition
      versus alcohol myopia model. Consuming alcohol increased acceptance of sexual
      aggression. Further, higher NSD and AIV scores were associated with acceptance of
      forced sex, but only after alcohol consumption. Overall, findings showed that key
      individual difference factors from Malamuth's Confluence Model enhance precision
      of predicting sexual aggression risk by young men under the influence of alcohol.

PMID- 19108957
TI  - Organizational-level correlates of the provision of detoxification services and
      medication-based treatments for substance abuse in correctional institutions.
AB  - In recent years, there has been an increased examination of organizational-level
      innovation adoption in substance abuse treatment organizations. However, the
      majority of these studies have focused on community-based treatment centers. One
      understudied area of the substance abuse treatment system is correctional
      institutions. This study uses the Criminal Justice Drug Abuse Treatment Studies
      (CJ-DATS) cooperative's National Criminal Justice Treatment Practices (NCJTP)
      survey to examine the adoption of detoxification services and pharmacotherapies
      for the treatment of substance abuse across a nationally representative sample of
      correctional institutions (n=198). There were significant differences between
      jails and prisons in the percentage of organizations offering detoxification
      services and medications. Specifically, detoxification services were offered by
      5% of prisons and 34% of jails; and, medications were offered by 6% of prisons
      and 32% of jails. Binary logistic regression models were used to examine the
      associations between these services and organizational characteristics, including
      context, resources, previously introduced practices, culture, and systems
      integration. Variables measuring organizational context and previously introduced
      practices were significant correlates of the provision of both detoxification
      services and medications. Multivariate results indicated that the differences
      between jails and prisons remained significant after controlling for other
      organizational factors. Although the adoption of detoxification services and
      pharmacotherapies may be a controversial topic for correctional institutions,
      these services have the potential to improve offender well-being and reduce
      public health risks associated with substance abuse.

PMID- 19108958
TI  - Using hepatitis C virus and herpes simplex virus-2 to track HIV among injecting
      drug users in New York City.
AB  - OBJECTIVE: To explore the potential utility of hepatitis C virus (HCV)
      seroprevalence as a biomarker for injection risk, and herpes simplex virus-2 (HSV
      2) as a biomarker for sexual risk among injecting drug users (IDUs). We examined
      the relationships between HCV and HIV and between HSV-2 and HIV among injecting
      drug users in New York City relative to the large-scale implementation of syringe
      exchange in the mid-1990s. METHODS: 397 injecting drug users were recruited from
      a drug detoxification program in New York from 2005 to 2007. Informed consent was
      obtained, a questionnaire covering demographics, drug use and HIV risk was
      administered. Blood samples were tested for antibody to HIV, HCV and HSV-2.
      RESULTS: Among all subjects, HIV prevalence was 17%, HCV prevalence 72% and HSV-2
      prevalence 48%. Among IDUs who began injecting before 1995, HIV was 28%, HCV
      serostatus was strongly associated with HIV serostatus (AOR=8.96, 95% CI 1.16
      69.04) and HSV-2 serostatus was not associated with HIV serostatus (AOR=1.31, 95%
      CI 0.64-2.67). Among subjects who began injecting in 1995 or later, HIV was 6%,
      HCV was not associated with HIV (AOR=1.04, 95% CI 0.27-4.08) and HSV-2 serostatus
      was strongly related to HIV serostatus (AOR=10.71, 95% CI 1.18-97.57).
      CONCLUSIONS: HCV and HSV-2 HCV and HSV-2 may provide important new tools for
      monitoring evolving HIV epidemics among IDUs. Reconsideration of the current CDC
      hierarchical transmission risk classification system may also be warranted.

PMID- 19108959
TI  - Contemporary neonatal outcome following rupture of membranes prior to 25 weeks
      with prolonged oligohydramnios.
AB  - BACKGROUND: Prolonged oligohydramnios following early preterm prelabour rupture
      of membranes (PPROM) is traditionally associated with high neonatal mortality and
      significant risk of pulmonary hypoplasia. However, recent evidence points to an
      apparent improvement in outcome. AIMS: To document current neonatal outcomes
      following rupture of membranes prior to 25 weeks with severe persistent
      oligohydramnios and a latency to delivery of at least 14 days. METHODS: A
      retrospective case note analysis over a 28-month period at Saint Luc University
      Hospital, Brussels. RESULTS: From 23 pregnancies that were complicated by PPROM
      prior to 25 weeks, 15 infants were born after 24 weeks with a latency of more
      than 14 days and persistent oligohydramnios. Nine infants (60%) had severe
      respiratory failure and clinical signs compatible with pulmonary hypoplasia.
      Seven of these infants (78%) responded to high frequency ventilation and inhaled
      nitric oxide therapy with good clinical outcome but two died from severe
      respiratory failure. Five infants showed no clinical signs of pulmonary
      hypoplasia and responded to conventional neonatal management. One of these
      infants died at 77 days of age of necrotising enterocolitis. One infant was not
      resuscitated and died within minutes of birth, following prior discussion with
      the perinatal team and the parents. Survivors in this high-risk group (73%) had
      low morbidity at the time of discharge. SUMMARY: The favourable neonatal survival
      and morbidity figures are in keeping with recent published evidence. This study
      confirms improved outcome even amongst the highest risk infants with documented
      persistent oligohydramnios.

PMID- 19108960
TI  - Evaluation of culture systems for attachment and proliferation of epithelial
      cells cultured from ovine semen.
AB  - Different culture systems were evaluated for their ability to support attachment
      and proliferation of the somatic cells obtained from ovine semen. Ejaculates
      (n=14) were collected from eight rams representing three breeds, Dorper, Suffolk
      and Hampshire. All samples were processed immediately and somatic cells were
      obtained from 11 of the 14 ejaculates. These cells had classic epithelial
      morphology and expressed cytokeratin, indicating they were of epithelial origin.
      Cells from four rams with the greatest growth rates were used for subsequent
      studies. Cells were cultured in four different media for 5 days and total numbers
      of attached cells vs. total numbers of seeded cells were counted and compared
      each day. Four media were evaluated: (1) a supplemented medium composed of
      DMEM/F12, 10% fetal bovine serum (FBS), 10 ng/ml epidermal growth factor, 30
      microg/ml bovine pituitary extract, 5 microg/ml insulin, 10 ng/ml cholera toxin,
      and 50 microg/ml gentamycin; (2) sheep fetal fibroblast (SFF)-conditioned medium;
      (3) swiss 3T3 fibroblast-conditioned medium; and (4) basic medium composed of
      DMEM/F12, 10% FBS, and 50 microg/ml gentamycin. Cell proliferation was greater in
      the supplemented medium, SFF-conditioned medium, and 3T3 fibroblast-conditioned
      medium compared to the basic medium by day 2 of culture (p<0.05, n=24), and
      greater in supplemented medium compared to the SFF-conditioned medium and 3T3
      fibroblast-conditioned medium by day 4 of culture (p<0.05, n=24). Three different
      surfaces: (1) Matrigel basement membrane matrix-coated plastic; (2) collagen I
      coated plastic; and (3) uncoated plastic were evaluated for their ability to
      support proliferation and attachment of the cells obtained from semen. Cell
      proliferation was greater when cells were cultured on the Matrigel-coated
      compared to the collagen I-coated and uncoated plastic by day 2 of culture
      (p<0.05, n=16). Cell attachment was greater when cells were plated on the
      Matrigel-coated and collagen I-coated plastic compared to the uncoated plastic
      (p<0.05, n=16). These studies describe an effective system for the culture and
      proliferation of epithelial cells obtained from ovine semen samples. The system
      may increase the likelihood of obtaining cells from frozen semen, which could be
      used for cloning to recover animals of genetic value in which semen is the only
      material that is available.

PMID- 19108961
TI  - Double freezing of bovine semen.
AB  - Fertility of bull spermatozoa cryopreserved in large volume by directional
      freezing technique, thawed, repackaged in straws and refrozen over liquid
      nitrogen vapor (double freezing, DF) was compared to conventional single freezing
      in straws (CF). Semen was collected from 6 bulls, 4 of which were selected for
      the field trial. Each semen collection was split into two parts, one frozen by CF
      and the other by DF. In vitro semen evaluations included motility (fresh, upon
      thawing and after 3h incubation at 37 degrees C), viability and acrosome
      integrity. A total of 3610 cows and heifers were randomly inseminated by either
      CF or DF at about equal numbers. In vitro sperm analysis indicated no difference
      between CF and directional freezing in large volume and both were superior to DF
      (P<0.001). Between-bull variations in fresh semen and in their reaction to CF or
      DF were apparent. Logistic regression analysis revealed that freezing method,
      bull, parity and inseminating technician, all had significant effect on pregnancy
      outcome (P< or =0.001 for all). Conception rate (CR) was 32.98% for CF and 28.05%
      for DF. Only in one bull conception rate by CF was significantly superior to DF
      (P<0.05). When divided into heifers, primi- and pluriparous cows, only the
      difference in CR between the pluriparous cows was significant (P=0.005). In
      conclusion, acceptable CR can be achieved by DF technique. These can be improved
      by selecting suitable bulls. The DF technique can be utilized in storage, sperm
      sexing and genome resource banking.

PMID- 19108962
TI  - Study of adverse outcomes in women using testosterone therapy.
AB  - OBJECTIVES: There are concerns that exogenous testosterone therapy may be
      associated with adverse cardiovascular effects, increases in risk of breast or
      uterus cancer and alterations in insulin sensitivity. Objective of this study was
      to explore the safety of testosterone therapy in actual clinical practice.
      METHODS: Data from the General Practice Research Database and the Health
      Improvement Network was used, including computerised medical records of UK
      general practitioners. The study population included women aged 18+ years
      prescribed testosterone, administered through implants (72.2%), tablets (18.4%)
      or injections (7.9%). Each testosterone user was matched by age and practice to
      three control patients. Cox proportional hazards models were used to compare the
      rates of several outcomes. RESULTS: The study population included 8412 women,
      2103 testosterone users and 6309 controls. There were no statistically
      significant differences between the cohorts in the rates of cerebrovascular
      disease, ischemic heart disease, breast cancer, deep venous thrombosis/pulmonary
      embolism, diabetes mellitus or acute hepatitis. The rate of breast cancer was
      comparable between testosterone users and control patients. The rate of
      androgenic events was increased in the testosterone cohort (relative rate of 1.55
      [95% CI 1.21-1.97]). Differences in outcomes between the cohorts were generally
      comparable across subgroups based on age and use of hormone therapy. CONCLUSIONS:
      This study found no major increase in the risk of cardiovascular diseases or
      breast cancer in women using testosterone (implants, tablets, or injections),
      while the risk of androgenic events was increased. It would be useful to conduct
      similar studies at lower doses with transdermal testosterone.

PMID- 19108963
TI  - Human SA gene polymorphisms are associated with non-high-density lipoprotein
      cholesterol in postmenopausal women: a pilot study.
AB  - OBJECTIVE: The purpose of the study is to evaluate the associations between
      polymorphisms of the human SA (SAH) gene, an acyl-CoA synthetase gene, with
      dyslipidemia and phenotypes of the insulin resistance syndrome in postmenopausal
      women. METHODS: One hundred and forty-two postmenopausal women were recruited for
      the study. Each subject received anthropometric and blood pressure measurements,
      fasting sampling for lipids, and a 75-g oral glucose tolerance test for insulin
      resistance. Genotypes of two polymorphisms in the promoter region (c.-962ins/del,
      c.-451G>A), one missense variant (c.1077G>C, p.K359N) in exon 8, and one in
      intron 12 (A>G) of the SAH gene, were determined. RESULTS: There were significant
      differences in genetic distribution of the SAH gene promoter I/D polymorphism
      between the two groups of subjects by non-high-density lipoprotein cholesterol
      (non-HDL-C) levels (p=0.004). The subjects with the DD genotype was associated
      with high levels of non-HDL-C (>160 mg/dL) as compared with the ID or II
      genotypes (p=0.002). Furthermore, three haplotypes were constructed based on the
      promoter I/D and the exon 8 G/C polymorphisms. Homozygosity for SAH haplotype 3
      was associated with increased adiposity, insulin resistance, and elevated levels
      of non-HDL-C in the post menopausal women. The subjects with haplotype 3 had
      double the risk to have higher non-HDL-C levels than those with haplotype 1.
      CONCLUSION: Our results suggest that the polymorphisms of the SAH gene are
      associated with non-HDL-C levels in postmenopausal women. Further studies with
      larger sample sizes or different populations are warranted to confirm our
      preliminary findings.

PMID- 19108964
TI  - Rapid analysis of methamphetamine in hair by micropulverized extraction and
      microchip-based competitive ELISA.
AB  - An automated full-range quantitation method for identifying d-methamphetamine in
      human hair using a microchip-based ELISA system (microELISA) in combination with
      a micropulverized extraction method for sample preparation has been developed. An
      antibody and a peroxidase-linked methamphetamine, both are commercially
      available, were used for the competitive ELISA assay. Method validation was
      carried out using doped hair samples, and segmental analyses of real-case
      specimens were carried out by both microELISA and LC/MS/MS to verify the
      reliability and applicability of this new method. Due to the small size of the
      system and the lack of an evaporation process, sample preparation and
      quantitation can be accomplished easily and quickly (less than 30 min) in small
      scale contamination-free environments.

PMID- 19108965
TI  - ToF-SIMS application in the visualization and analysis of fingerprints after
      contact with amphetamine drugs.
AB  - Time-of-flight secondary ion mass spectrometry was applied in forensic research
      for characterization, visualization and analysis of fingerprints left after the
      fingers were contaminated by traces of drugs: amphetamine (AF), methamphetamine
      (MA) and methylenedioxymethamphetamine (MDMA; ecstasy). Experimental work was
      carried out using four kinds of bases (steel, aluminium, brass and glass) on
      which fingerprints were imprinted. The results of our preliminary studies have
      demonstrated that the ToF-SIMS technique can be a powerful tool in chemical
      investigations of fingerprints and detection of traces of substances, which do
      not exist in natural skin extraction, but can be found at the crime scene.

PMID- 19108966
TI  - [Incidence, prevalence and risk factors for a first infectious complication on a
      totally implantable venous-access port].
AB  - BACKGROUND: Totally implantable venous-access ports (TIVAP) should present less
      risk of complications than central venous catheters over a long time period.
      AIMS: Firstly, the study's objective was to assess the prevalence and incidence
      of a first infectious complication on a TIVAP and secondly, to assess the risk
      factors associated with this first infection. METHODS: The authors made a
      longitudinal historical cohort study of patients with a TIVAP in 2003, in the
      Dijon University Hospital. RESULTS: Two hundred and nineteen patients (sex-ratio
      1.9) were included, with a total follow-up of 92,773 patients-days. Ninety
      percent of the TIVAP were used for chemotherapy, 5% for antibiotic drug
      administration, 2% for parenteral nutrition and 3% for other reasons (recurrent
      blood transfusions, etc.). Overall, 34 (16.3%) out of 209patients presented with
      at least one infectious complication, with an incidence rate of
      0.37infection/1,000patients-days. The 5-year cumulative probability to be free of
      infectious complication was only 62.8%. In multivariate analysis, only underlying
      hematological neoplasia (by contrast with solid tumors) was significantly
      associated to a higher risk of infectious complication. CONCLUSIONS: The
      infectious risk linked to the use of TIVAP is significant, higher in case of
      underlying hematological neoplasia and during the first months of use.

PMID- 19108967
TI  - [Disseminated strongyloidiasis with parasitemia in a patient under corticosteroid
      treatment].
AB  - We report a case of disseminated strongyloidiasis with parasitemia in a 53-year
      old man under corticosteroid therapy. It occurred more than 16years after
      contamination and led to severe sepsis and acute respiratory failure with P.
      aeruginosa pneumonia. The patient recovered after specific treatment
      (thiabendazole followed by albendazole) and antibacterial drugs.

PMID- 19108968
TI  - [Liver transplantation for hepatocellular carcinoma].

PMID- 19108969
TI  - [Hepatic transplantation].

PMID- 19108970
TI  - Diagnostic imaging of the inflammatory bowel disease.

PMID- 19108971
TI  - Diagnostic imaging in Merkel cell carcinoma: lessons to learn from 16 cases with
      correlation of sonography, CT, MRI and PET.
AB  - OBJECTIVE: The authors report imaging findings in a series of 16 patients with
      MCC, a rare tumour which is often managed primarily by a dermatologist. To our
      knowledge, no equivalent series of MCC has been described in the nuclear medicine
      literature. MATERIAL AND METHODS: In this IRB-approved retrospective
      noncomparative case series 16 patients with biopsy-proven Merkel cell carcinoma
      were included between January 1999 and October 2007. Twenty-nine whole body PET
      scans (18F-FDG n=24, 18F-FDOPA n=5) in 16 patients were retrospectively reviewed
      with regard to tracer uptake in six anatomical sites per patient. For 127/144 of
      FDG-PET evaluated regions and 68/144 of regions depicted by conventional imaging
      methods, a valid standard of reference could be obtained. A combined standard of
      reference was applied, which consisted of histopathology (lymphadenectomy or
      biopsy) or clinical or radiological follow-up for at least 12 months. RESULTS:
      the mean FDG uptake over the clinicopatholigical verified FDG avid areas was 4.7
      SUV (1.5-9.9 SUV). The region based assessment of diagnostic value, in
      consideration of the standard of reference, resulted in a sensitivity of 85.7%
      and a specificity of 96.2% of FDG-PET (n=127) and in a combined sensitivity of
      95.5% and a specificity of 89.1% for morphological imaging methods (n=68).
      Differences between methods did not reach statistical significance (p=1.00,
      p=0.18). CONCLUSIONS: FDG-PET is a highly useful whole body staging method of
      comparable value compared to conventional imaging methods with restricted field
      of view. The lessons learned from case series are discussed.

PMID- 19108972
TI  - Routine use of modified CT Enterography in patients with acute abdominal pain.
AB  - PURPOSE: To evaluate routine use of CT Enterography (CTE) in patients presenting
      with non-traumatic acute abdominal pain with respect to patient tolerance,
      imaging of intestinal detail along with conventional abdominal evaluation.
      MATERIALS AND METHODS: Modified CTE was performed in 165 consecutive patients
      with acute abdominal pain: ingestion, as tolerated, of 900-1200 ml of 2% barium
      suspension + 5 ml of Gastrografin over 45 min; 150 ml of iv contrast given in two
      boluses (50 and 100 ml) 3 min apart (split bolus injection protocol). Axial,
      coronal and sagittal reformats were reviewed by two radiologists and graded on a
      5-point scale (5 best) in regard to GI tract luminal opacification and distension
      and abdominal organ and vascular enhancement. RESULTS: In 81 patients the cause
      of abdominal pain was identified (intestinal in 54 and extraintestinal in 27).
      Oral contrast reached cecum in 76% of the patients and the small bowel was well
      distended and opacified (medians=4). Mucosa detail was good (median=3) and there
      was significant (p<0.0001) correlation between bowel opacification and distension
      for both jejunum and ileum. A combined nephrographic and excretory phase was
      achieved (medians 4 and 5, respectively), while the great vessels were well
      opacified, allowing for vascular evaluation (median=5). The rest of the abdominal
      structures were well visualized. CONCLUSION: Modified CTE is well tolerated by
      patients with acute non-traumatic abdominal pain, and can be used routinely as a
      non-invasive examination informative of bowel, vessel and organ pathology in
      Emergency Department patients.

PMID- 19108973
TI  - Chronic lower extremity lymphedema: a comparative study of high-resolution
      interstitial MR lymphangiography and heavily T2-weighted MRI.
AB  - PURPOSE: To assess the role of heavily T2-weighted image and interstitial MR
      lymphangiography (MRL) for the visualization of lymphatic vessels in patients
      with disorders of the lymphatic circulation. METHODS: Forty lower extremities in
      31 patients (9 bilateral and 22 unilateral) with primary lymphedema were examined
      by heavily T2-weighted image and indirect MRL. Maximum-intensity projection (MIP)
      was used to reconstruct the images of the lymphatic system. Two experienced
      radiologists analyzed the images with regard to the differences in image quality,
      number of lymphatic vessels, its maximum diameter and two other findings:
      accumulated lymph fluid in the tissue and honeycombing pattern. RESULTS: The
      beaded appearance of the affected vessels in 73 leg segments of 40 lower
      extremities were present on both modalities 3D MIP. Larger amount of the dilated
      lymphatic vessels were visualized on heavily T2-weighted image than that on MRL
      (p=0.003) and the maximum diameter of it was 4.28+/-1.53mm on heavily T2-weighted
      image, whereas 3.41+/-1.05mm on MRL (p<0.01). The dilated lymphatic vessels on
      MRL showed better image quality and greater SNR and CNR than that on heavily T2
      weighted image (p<0.01). The regions of accumulated lymph fluid and the
      honeycombing pattern extent were identified on heavily T2-weighted image scored
      statistically higher than that on MRL (p<0.01). CONCLUSION: The heavily T2
      weighted imaging has greater sensitivity and the MRL image has higher legibility
      for detecting the pathologically modified lymphatic vessels and accompanying
      complications non-invasively. Combining these two MR techniques can accurately
      access the pathological changes in the lower extremity with lymphedema.

PMID- 19108974
TI  - Feasibility of magnetic resonance imaging-guided high intensity focused
      ultrasound therapy for ablating uterine fibroids in patients with bowel lies
      anterior to uterus.
AB  - PURPOSE: To prospectively evaluate the feasibility of magnetic resonance (MR)
      imaging-guided high intensity focused ultrasound (HIFU) therapeutic ablation of
      uterine fibroids in patients with bowel lies anterior to uterus. MATERIALS AND
      METHODS: Twenty-one patients with 23 uterine fibroids underwent MR imaging-guided
      high intensity focused ultrasound treatment, with a mean age of 39.4+/-6.9 (20
      49) years, with fibroids average measuring 6.0+/-1.6 (range, 2.9-9.5)cm in
      diameter. After being compressed with a degassed water balloon on abdominal wall,
      MR imaging-guided high intensity focused ultrasound treatment was performed under
      conscious sedation by using fentanyl and midazolam. This procedure was performed
      by a Haifu JM focused ultrasound tumour therapeutic system (JM2.5C, Chongqing
      Haifu Technology Co., Ltd., China), in combination with a 1.5-Tesla MRI system
      (Symphony, Siemens, Germany), which provides real-time guidance and control.
      Contrast-enhanced MR imaging was performed to evaluate the efficacy of thermal
      ablation immediately and 3 months after HIFU treatment. The treatment time and
      adverse events were recorded. RESULTS: The mean fibroid volume was 97.0+/-78.3
      (range, 12.7-318.3)cm(3). According to the treatment plan, an average 75.0+/
      11.4% (range, 37.8-92.4%) of the fibroid volume was treated. The mean fibroid
      volume immediately after HIFU was 109.7+/-93.1 (range, 11.9-389.6)cm(3), slightly
      enlarged because of edema. The average non-perfused volume was 83.3+/-71.7
      (range, 7.7-282.9)cm(3), the average fractional ablation, which was defined as
      non-perfused volume divided by the fibroid volume immediately after HIFU
      treatment, was 76.9+/-18.7% (range, 21.0-97.0%). There were no statistically
      significant differences between the treatment volume and the non-perfused volume.
      Follow-up magnetic resonance imaging (MRI) at 3 months obtained in 12 patients,
      the fibroid volume decreased by 31.4+/-29.3% (range, -1.9 to 60.0%) in average,
      with paired t-test showing a statistically significant reduction (P=0.002). The
      mean treatment time for ablating the average 83.3+/-71.7 (range, 7.7-282.9)cm(3)
      of fibroid volume was 2.5+/-1.4h (range, 27-390min) in this study, which was
      relatively short and acceptable to patient and therapist. Four patients
      experienced mild skin burn (two with skin redness, two with blisters), the skin
      burn subsided within approximately 2 days. No other adverse events were observed.
      CONCLUSIONS: After the bowel was compressed with a degassed water balloon, MR
      imaging-guided high intensity focused ultrasound treatment is safe and feasible
      in ablating uterine fibroids in patients with bowel lies anterior to uterus.

PMID- 19108975
TI  - Effect of seed sludge and operation conditions on performance and archaeal
      community structure of low-temperature anaerobic solvent-degrading bioreactors.
AB  - Two laboratory-scale expanded granular sludge bed (EGSB) anaerobic bioreactors
      (R1 and R2) were inoculated with biomass from different mesophilic (37 degrees C)
      treatment plants, and used for the treatment of an organic solvent-based
      wastewater at 9-14 degrees C at applied organic loading rates (OLRs) of 1.2-3.6kg
      chemical oxygen demand (COD)m(-3)d(-1). Replicated treatment performance was
      observed at 10-14 degrees C, which suggested the feasibility of the process at
      pilot-scale. Stable and efficient COD removal, along with high methane
      productivity, was demonstrated at 9 degrees C at an applied OLR of 2.4kgCODm(
      3)d(-1). Clonal libraries and fluorescence in situ hybridization (FISH) indicated
      that the seed sludges were dominated (>60%) by acetoclastic Methanosaeta-like
      organisms. Specific methanogenic activity (SMA) profiles indicated shifts in the
      physiological profiles of R1 and R2 biomass, including the development of
      psychrotolerant methanogenic activity. Acetoclastic methanogenesis represented
      the primary route of methane production in R1 and R2, which is in contrast with
      several previous reports from low-temperature bioreactor trials. A reduction in
      the abundance of Methanosaeta-like clones (R2), along with the detection of
      hydrogenotrophic methanogenic species, coincided with altered granule (sludge)
      morphology and the development of hydrogenotrophic SMA after prolonged operation
      at 9 degrees C.

PMID- 19108976
TI  - Short-echo-time magnetic resonance spectroscopy of single voxel with arbitrary
      shape in the living human brain using segmented two-dimensional selective
      radiofrequency excitations based on a blipped-planar trajectory.
AB  - The target regions of single-voxel MR spectroscopy often deviate from the
      cuboidal volume acquired with localization methods based on cross-sectional RF
      excitations. To diminish partial volume effects spatially 2D-selective RF
      excitations (2DRF) have been used to excite anatomically defined regions of
      interest (ROIs). Thereby, segmentation of the 2DRF has been applied to avoid
      excessive pulse durations yielding "virtual" excitation profiles that are defined
      upon averaging multiple acquisitions obtained with the different segments. In
      this work, the feasibility of segmented 2DRF for single-voxel (1)H-MR
      spectroscopy of arbitrarily shaped voxel in the living human brain is
      demonstrated. The 2DRF segments were chosen to cover a single line of a blipped
      planar trajectory in order to minimize chemical shift displacement artifacts and
      achieve standard echo times of 30 ms. To eliminate unwanted side excitations, a
      refocusing RF excitation in the blip direction was used. Phantom experiments
      demonstrate the high spatial selectivity achieved, i.e., the absence of
      significant signal contaminations from regions outside of the target volume.
      Although the signal obtained per volume is reduced compared to cross-sectional
      localization, the better volume coverage of anatomically defined ROIs can deliver
      an improved signal-to-noise ratio for irregularly shaped ROIs.

PMID- 19108977
TI  - Stability of selected chlorinated thiazide diuretics.
AB  - In sports, diuretics are used for two main reasons: to flush previously taken
      prohibited substances with forced diuresis and in sports where weight classes are
      involved to achieve acute weight loss. A common property observed for thiazides
      is hydrolysis in aqueous media resulting in the formation of the degradation
      product aminobenzenedisulphonamide. This degradation product can be observed for
      several thiazides. Because there is limited information regarding the effect of
      pH, temperature and light on the stability of thiazides, these parameters were
      investigated for chlorothiaizide, hydrochlorothiazide and altizide. For all three
      compounds the degradation product could be detected after incubation at pH 9.5
      for 48h at 60 degrees C. At lower pH and temperature the degradation product
      could not be detected for all compounds. When samples were exposed to UV-light
      altizide and hydrochlorothiazide were photodegraded to chlorothiazide. When the
      degradation rate between the different compounds was compared for a given
      temperature and pH, altizide is the most unstable compound. This study confirms
      that thiazide degradation products can be formed in urine during transport. Hence
      doping control laboratories shall include them into their routine testing methods
      as required by WADA.

PMID- 19108978
TI  - 2D and 3D DOSY 1H NMR, a useful tool for analysis of complex mixtures:
      application to herbal drugs or dietary supplements for erectile dysfunction.
AB  - Seventeen herbal dietary supplements, marketed as natural substances for the
      enhancement of sexual function, were analyzed by diffusion ordered spectroscopy
      (DOSY) (1)H NMR. The method allowed a global analysis of the samples with
      detection of both active and inactive ingredients present in these complex
      matrixes. Eight formulations contained compounds related to the synthetic
      phosphodiesterase-5 inhibitors. Sildenafil, tadalafil, vardenafil,
      hydroxyhomosildenafil, thiosildenafil, and the newly identified adulterant
      thiomethisosildenafil were detected. Quantification of these active ingredients
      was carried out by HPLC or NMR. In addition to these actives, about 30 compounds
      or excipients were characterized. This study ended up with a three-dimensional
      DOSY-COSY (1)H NMR experiment on a herbal formulation which provided both virtual
      separation and structural information.

PMID- 19108979
TI  - Providing counseling on alcohol use for patients with liver disease: another
      missed opportunity.

PMID- 19108980
TI  - Comments about article: induced hypothermia and fever control for prevention and
      treatment of neurological injuries.

PMID- 19108981
TI  - [Toxic shock syndrome consecutive to the presence of vaginal tampon for
      menstruation regressive after early haemodynamic optimization and activated
      protein C infusion].
AB  - A 19-year-old woman was admitted in the intensive care unit for a septic shock
      recognized as a menstrual toxic shock syndrome with a Staphylococcus aureus. An
      early goal oriented therapy was started in order to correct in particular the
      venous central O(2) saturation (ScvO(2)) associated to an early empiric anti
      infectious treatment. A multi-organ failure appeared in a second time, so that we
      began a protein C activated infusion. The outcome was also auspicious.
      Bacteriologic samples and specific samples for the research of Staphylococci
      toxins confirmed the diagnosis of toxic shock syndrome with Staphylococcus
      aureus. A genotypic study allowed us to identify many anomalies which could be
      involved in the incompletely understood physiopathology of this disease.

PMID- 19108982
TI  - [Airway management for anaesthesia performed at the end of labour: survey of
      practices].
AB  - OBJECTIVE: To describe the airway management during general anaesthesia performed
      at the end of labour. STUDY DESIGN: Observational retrospective study in a French
      university obstetrical unit. PATIENTS AND METHODS: All parturients who underwent
      general anaesthesia for manual removal of the placenta or instrumental delivery
      were included. Demographic data, anaesthesia management, indication and duration
      of anaesthesia were recorded. Incidents as vomiting, a drop in oxygen saturation
      of five points or more, aspiration and difficult endotracheal intubation were
      investigated. RESULTS: Among 111 parturients with inclusion criteria, the rate of
      tracheal intubation was 5%. The duration of anaesthesia ranged from five to 60
      minutes (mean duration: 16 min). No incident was recorded within the
      methodological limits of this retrospective study. CONCLUSION: There is a major
      discrepancy between guidelines and clinical practice in our unit concerning
      systematic tracheal intubation during general anaesthesia performed at the end of
      labour. A national survey is in process to confirm these results.

PMID- 19108983
TI  - OCD cognitions and symptoms in different religious contexts.
AB  - Religious themes commonly feature in obsessions. Some theorists view religiosity
      as a potential risk factor, due to the hypothesized influence of religious
      acculturation on appraisals of unwanted intrusive thoughts. Several studies
      revealed that the relationship between religiosity and some OCD cognitions might
      change among various religions, possibly because of the differences in religious
      doctrines and teachings. The present study examined the relationship between
      religiosity and OCD symptoms and cognitions in different religious contexts. In
      this study, Muslim and Christian subjects from Turkey and Canada, respectively,
      were compared on OCD features by taking their level of religiosity into
      consideration. The results showed that having scored higher in OCD symptoms,
      Muslim participants reported more concerns on their thoughts and controlling
      them, and they also seemed to use worry strategy to manage their unwanted
      thoughts. On the other hand, regardless of religion category, high religious
      subjects reported to experience more obsessional thoughts and checking, while
      sensitivity on thoughts and emphases on control of thoughts and psychological
      fusion in morality were more salient for this group. Indeed, degree of
      religiosity also made a significant difference on thought-action fusion in
      morality domain especially for Christian subjects. In line with previous
      findings, the results of the present study support the association between
      religiosity and OCD even across two monotheistic religions. Besides, the
      characteristics of the religion might account for the differences in OCD
      cognitions and symptoms across both religions.

PMID- 19108985
TI  - Hierarchical modeling gave plausible estimates of associations between metabolic
      syndrome and components of antiretroviral therapy.
AB  - OBJECTIVE: Hierarchical modeling has been proposed as a solution to the multiple
      exposure problem. We estimate associations between metabolic syndrome and
      different components of antiretroviral therapy using both conventional and
      hierarchical models. STUDY DESIGN AND SETTING: We use discrete time survival
      analysis to estimate the association between metabolic syndrome and cumulative
      exposure to 16 antiretrovirals from four drug classes. We fit a hierarchical
      model where the drug class provides a prior model of the association between
      metabolic syndrome and exposure to each antiretroviral. RESULTS: One thousand two
      hundred and eighteen patients were followed for a median of 27 months, with 242
      cases of metabolic syndrome (20%) at a rate of 7.5 cases per 100 patient years.
      Metabolic syndrome was more likely to develop in patients exposed to stavudine,
      but was less likely to develop in those exposed to atazanavir. The estimate for
      exposure to atazanavir increased from hazard ratio of 0.06 per 6 months' use in
      the conventional model to 0.37 in the hierarchical model (or from 0.57 to 0.81
      when using spline-based covariate adjustment). CONCLUSION: These results are
      consistent with trials that show the disadvantage of stavudine and advantage of
      atazanavir relative to other drugs in their respective classes. The hierarchical
      model gave more plausible results than the equivalent conventional model.

PMID- 19108986
TI  - Comparison of the pre-post and transition question assessments in a health
      education setting.
AB  - OBJECTIVE: This study examined the classical pre-intervention/post-intervention
      assessment (pre-post) and the single post-intervention transition question
      assessment (transition question) to determine how well these methods reflected
      qualitative interview-based participant-reported outcomes from chronic disease
      self-management education programs (CDSMEPs). STUDY DESIGN AND SETTING: A mixed
      method qualitative and quantitative approach was applied in 25 interviews with
      participants recruited from CDSMEPs within Australia. Qualitative interviews with
      participants were used as a relative "gold standard" and compared with
      questionnaire-based pre-post and transition question assessments. RESULTS:
      Comparison of the two questionnaire-based assessments showed that most of the
      individual paired responses were discordant (61%). Using participant's
      qualitative narratives as a "true" indicator, the pre-post assessment was found
      on more occasions to be discordant with participant-reported outcomes than the
      transition question. The origin of the inconsistency was largely because of a
      change in respondents' perspective that had occurred after pretest, which was
      mediated by CDSMEPs' experiences and insights. CONCLUSION: This study suggests
      that the pre-post assessment has poor validity for the assessment of health
      education program outcomes. Alternative assessments, such as the transition
      question, may result in a more accurate reflection of the impact of such programs
      on participants.

PMID- 19108984
TI  - Self-reported stroke and myocardial infarction had adequate sensitivity in a
      population-based prospective study JPHC (Japan Public Health Center)-based
      Prospective Study.
AB  - OBJECTIVE: We sought to clarify the validity of self-reported stroke and
      myocardial infarction (MI) among Japanese population, because information on the
      validity, particularly on the sensitivity, of self-reported cardiovascular
      disease is limited and may differ among countries. STUDY DESIGN AND SETTING:
      Using the 10-year follow-up questionnaire and a stroke and MI registry in the
      Japan Public Health Center-based prospective Study (JPHC Study) cohort
      (n=91,186), we calculated sensitivity and positive predictive values of self
      reported stroke and MI incidence over 10 years. RESULTS: Sensitivity of self
      reported incident stroke was 73%, and that for MI was 82%. Positive predictive
      values were 57% for stroke and 43% for MI. The supplemental inclusion of self
      reported angina pectoris increased the sensitivity of MI to 89%, but attenuated
      the positive predictive value to 18%. Sensitivity of self-reported stroke was
      highest for subarachnoid hemorrhage (88%), but did not differ greatly among other
      stroke subtypes, affected sites or size. CONCLUSION: Self-reported stroke and MI
      seem sensitive enough to use for exclusion of stroke and MI at baseline in
      Japanese cohort studies. However, self-report has too many false positives to be
      used as the only criterion for incident stroke and MI.

PMID- 19108987
TI  - Cross-cohort heterogeneity encountered while validating a model for HIV disease
      progression among antiretroviral initiators.
AB  - OBJECTIVE: To evaluate a model for predicting time to AIDS or death among HIV
      infected persons initiating highly active antiretroviral therapy (HAART). STUDY
      DESIGN AND SETTING: The model was constructed from 1,891 HAART initiators in the
      Collaborations in HIV Outcomes Research/US (CHORUS) cohort. The model's
      predictive ability was assessed using internal bootstrap validation techniques
      and data from 716 HAART initiators at Johns Hopkins HIV Clinical Cohort (JHHCC)
      in whom HIV disease was, in general, more advanced. RESULTS: The estimated
      concordance statistic was 0.632 with the bootstrap method and 0.625 in JHHCC.
      Mean predicted and observed 3-year AIDS-free survival for JHHCC was 0.76 and 0.73
      (95% confidence interval [CI], 0.69-0.77), respectively; mean predicted and
      observed 5-year AIDS-free survival was 0.69 and 0.57 (95% CI, 0.52-0.62),
      respectively. Sensitivity analyses showed that the discrepancy between predicted
      and observed AIDS-free survival after 3 years could be due to differences in lost
      to-follow-up rates between cohorts. CONCLUSION: The model was fair at using
      baseline characteristics to order patients' risk of disease progression, but did
      not accurately predict AIDS-free survival >3 years after HAART initiation.
      Different variable definitions, patient characteristics, and loss to follow-up
      highlight the challenges of using data from one cohort to predict AIDS-free
      survival in an independent cohort.

PMID- 19108988
TI  - Mixed models showed no need for initial response monitoring after starting
      antihypertensive therapy.
AB  - OBJECTIVE: To demonstrate how mixed models may be used to estimate treatment
      effects, and inform decisions on the need for monitoring initial response. STUDY
      DESIGN AND SETTING: Mixed models were used to analyze data from the Perindopril
      Protection Against Recurrent Stroke Study (PROGRESS), which examined the effects
      of perindopril and indapamide in 6,105 patients at high risk of a cerebrovascular
      event. RESULTS: The mean effect of perindopril was to lower blood pressure (BP)
      (systolic/diastolic) by 6/3 mmHg. The mean effects of perindopril/indapamide
      varied according to baseline BP, and lowering of BP ranged from 9/5 to 14/5 mmHg
      (for individuals with a baseline systolic BP <140 and >150 mmHg, respectively).
      We found no variation in the effects of treatment on BP for either perindopril
      alone or in combination with indapamide. The effects of treatment on the
      individual can be predicted from the mean effect of treatment for the group
      (perindopril) or baseline systolic BP subgroup (perindopril/indapamide).
      CONCLUSION: Monitoring initial treatment response is unnecessary for
      antihypertensives similar to those examined in this study. To address this issue
      for other therapies, we suggest that trials should report estimates of treatment
      effects from mixed models, and the CONSORT statement should be expanded to
      include this item.

PMID- 19108990
TI  - A new approach to arthrocentesis of the temporomandibular joint.
AB  - We describe a new temporomandibular joint (TMJ) arthrocentesis technique using
      the irrigation pump from a surgical and dental implant motor, providing the
      highest hydraulic pressure reported in the literature for TMJ lavage.

PMID- 19108989
TI  - Pro-inflammatory genotype as a risk factor for aPL-associated thrombosis: Report
      of a family with multiple anti-phospholipid positive members.
AB  - OBJECTIVE: Inflammation might represent a second hit for anti-phospholipid
      antibody (aPL)-mediated thrombosis. Inflammatory responses have been linked to
      gene polymorphisms of several cytokines and Toll Like Receptors (TLRs). We
      examined IL1 beta, TNFalpha, TGFbeta, IL6, IFN gamma, IL10, tlr4 gene
      polymorphisms in a family with several members positive for IgG anti-beta2
      glycoprotein I (beta 2GPI) antibodies but with recurrent thrombosis in one member
      only. METHODS: Lupus anticoagulant, anti-cardiolipin, anti-beta 2GPI IgG/IgM
      antibodies, IL1beta, TNFalpha, TGF beta1, IL6, IL10, IFN gamma, tlr4 gene
      polymorphisms (by allele-specific polymerase chain reaction) in addition to
      standard thrombophilic risk factors and cytokine serum levels (IL-1 beta,
      TNFalpha, IL-10) were evaluated. RESULTS: Recurrent thrombotic events was
      reported only in the proband, but not in three healthy siblings persistently
      positive for IgG anti-beta2GPI antibodies, respectively. The wild type tlr4 gene
      and cytokine polymorphisms associated with a high pro-inflammatory response (IL-1
      beta promoter-511C/T; TNFalpha G/A; TGFbeta+10T/C, +25C/G; IL-6 -174C/G) were
      found only in the proband. Serum cytokine levels were normal. CONCLUSION: This
      case report confirms that protective tlr4 gene polymorphisms are more frequent in
      asymptomatic aPL carriers. In line with the role of inflammatory mediators as
      second hits for aPL-associated thrombosis, the polymorphisms of cytokines linked
      to higher inflammatory response were found in the proband only.

PMID- 19108991
TI  - Effects of locally applied nerve growth factor to the inferior alveolar nerve
      histology in a rabbit model of mandibular distraction osteogenesis.
AB  - Distraction osteogenesis (DO) is widely used in deformities and defects of the
      craniofacial bone. Accelerating inferior alveolar nerve (IAN) recovery would aid
      the process. Nerve growth factor (NGF) plays a vital role in peripheral nerve
      regeneration. In this study, the ability of locally applied human NGF beta
      (hNGFbeta) to enhance the morphological recovery of the IAN in a rabbit model of
      mandibular DO was studied. Rabbits underwent bilateral DO with a rate of 0.5mm
      per 12h. Two doses of 40 microg hNGFbeta in buffer were injected into callus at
      the beginning the of consolidation time. The contralateral side received
      injections of placebo. Rabbits were killed at 14 and 28 days. IAN specimens were
      subjected to histological and histomorphometric analysis. In both 14 and 28 days
      consolidation experiments, nerve histological analysis showed less degeneration
      and more regeneration in nerve fibers on the hNGFbeta treated side than the
      control side. Histomorphometric analysis showed that the myelinated fiber density
      on the hNGFbeta treated side was significantly higher than on the control side
      (p<0.01). The data indicate that locally applied hNGFbeta can accelerate the
      morphological recovery of the IAN and may play a role in reducing nerve injury in
      mandibular DO clinically.

PMID- 19108992
TI  - Neurological abnormalities among offspring of persons with schizophrenia:
      relation to premorbid psychopathology.
AB  - BACKGROUND: Neurological Examination Abnormalities (NEA, often called
      "neurological soft signs") have been observed in early schizophrenia and may be
      heritable. We investigated the prevalence, and neurocognitive and
      psychopathological correlates of NEA among offspring of schizophrenia patients
      who are at increased genetic risk for this illness. METHODS: Neurological
      examinations were conducted on high risk (HR, n=74) and healthy comparison
      subjects (HS, n=86), using the Heinrichs-Buchanan scale. Cognitive-perceptual
      (CogPer) and repetitive motor (RepMot) subscores, and total NEA scores were
      computed. All HR and HS were assessed using K-SADS/SCID for diagnoses. Schizotypy
      was measured using the Magical Ideation and the Perceptual Aberration subscales
      (Chapman scale), attention using Continuous Performance Test (CPT-IP) and
      executive functions using the Wisconsin Card Sorting Test (WCST). RESULTS: CogPer
      (F(1,160)=7.14, p=0.008) but not RepMot NEA scores were higher in HR subjects
      compared to HS after controlling for age and sex. CogPer NEA scores were higher
      in HR subjects with axis I psychopathology compared to those without (F(2,170)
      6.41, p=0.002). HR subjects had higher schizotypy scores (composite of the
      magical ideation and perceptual aberration scales) (F(1,141)=23.25, p=0.000004).
      Schizotypy scores were negatively correlated with sustained attention and
      executive functions. In addition, schizotypy was positively correlated with
      CogPer NEA scores. CONCLUSIONS: Young relatives at increased genetic risk for
      schizophrenia show more frequent NEA. CogPer but not RepMot NEA scores were
      elevated, consistent with our prior observation of CogPer NEA being relatively
      specific for schizophrenia. The observed relationships between NEA, cognitive
      impairments, schizotypy and axis I disorders suggest that NEA may characterize a
      subgroup of HR offspring at an elevated risk for psychopathology.

PMID- 19108993
TI  - A VIM-1 metallo-beta-lactamase-producing Klebsiella pneumoniae clinical isolate
      in an acute hospital in Germany.

PMID- 19108994
TI  - Anti-HIV drugs: 25 compounds approved within 25 years after the discovery of HIV.
AB  - In 2008, 25 years after the human immunodeficiency virus (HIV) was discovered as
      the then tentative aetiological agent of acquired immune deficiency syndrome
      (AIDS), exactly 25 anti-HIV compounds have been formally approved for clinical
      use in the treatment of AIDS. These compounds fall into six categories:
      nucleoside reverse transcriptase inhibitors (NRTIs: zidovudine, didanosine,
      zalcitabine, stavudine, lamivudine, abacavir and emtricitabine); nucleotide
      reverse transcriptase inhibitors (NtRTIs: tenofovir); non-nucleoside reverse
      transcriptase inhibitors (NNRTIs: nevirapine, delavirdine, efavirenz and
      etravirine); protease inhibitors (PIs: saquinavir, ritonavir, indinavir,
      nelfinavir, amprenavir, lopinavir, atazanavir, fosamprenavir, tipranavir and
      darunavir); cell entry inhibitors [fusion inhibitors (FIs: enfuvirtide) and co
      receptor inhibitors (CRIs: maraviroc)]; and integrase inhibitors (INIs:
      raltegravir). These compounds should be used in drug combination regimens to
      achieve the highest possible benefit, tolerability and compliance and to diminish
      the risk of resistance development.

PMID- 19108995
TI  - Microencapsulation of tamoxifen: application to cotton fabric.
AB  - Tamoxifen microcapsules and drug loaded medicated fabrics were investigated. The
      microcapsules were prepared using a complex coacervation procedure involving
      gelatin B and acacia gum. The morphology, particle size, drug loading capacity
      and in vitro release characteristics of the drug microcapsules were optimized for
      coating tamoxifen microcapsules onto the cotton fabrics. Infrared (IR) spectra
      and SEM were used to characterize the medicated fabrics and air permeability and
      laundering testing were undertaken to determine the efficiency and effectiveness
      of the system. Results showed that optimum condition for the microcapsules was at
      drug/polymer ratio 1:4, polymer concentration 3%, and rate of stirring 1000 rpm.
      In vitro release assays demonstrated that the tamoxifen was liberated over 10h
      after an initial bust rate period. SEM images illustrated that the tamoxifen
      microcapsules were spherical in shape and were also tightly fixed on to the
      cotton fabrics fast. These observations demonstrate that we have designed and
      fabricated a medicated system that potentially could be applied within a
      transdermal drug delivery system and so act in a system for the treatment of
      breast cancer.

PMID- 19108996
TI  - Characterization of biomaterials polar interactions in physiological conditions
      using liquid-liquid contact angle measurements: relation to fibronectin
      adsorption.
AB  - Wettability of biomaterials surfaces and protein-coated substrates is generally
      characterized with the sessile drop technique using polar and apolar liquids.
      This procedure is often performed in air, which does not reflect the
      physiological conditions. In this study, liquid/liquid contact angle measurements
      were carried out to be closer to cell culture conditions. This technique allowed
      us to evaluate the polar contribution to the work of adhesion between an aqueous
      medium and four selected biomaterials widely used in tissue culture applications:
      bacteriological grade polystyrene (PS), tissue culture polystyrene (tPS), poly(2
      hydroxyethyl methacrylate) film (PolyHEMA), and hydroxypropylmethylcellulose
      carboxymethylcellulose bi-layered Petri dish (CEL). The contributions of polar
      interactions were also estimated on the same biomaterials after fibronectin (Fn)
      adsorption. The quantity of Fn adsorbed on PS, tPS, PolyHEMA and CEL surfaces was
      evaluated by using the fluorescein-labeled protein. PolyHEMA and CEL were found
      to be hydrophilic, tPS was moderately hydrophilic and PS was highly hydrophobic.
      After Fn adsorption on PS and tPS, a significant increase of the surface polar
      interaction was observed. On PolyHEMA and CEL, no significant adsorption of Fn
      was detected and the polar interactions remained unchanged. Finally, an inverse
      correlation between the polarity of the surfaces and the quantity of adsorbed Fn
      was established.

PMID- 19108997
TI  - The interaction between PAMAM G3.5 dendrimer, Cd2+, dendrimer-Cd2+ complexes and
      human serum albumin.
AB  - The interactions between PAMAM G3.5 dendrimer, Cd2+, a complex of "PAMAM G3.5
      dendrimer-Cd2+" and human serum albumin were studied by equilibrium dialysis,
      fluorescence quenching, fluorescence anisotropy and zeta-potential. It was found
      that in water one molecule of PAMAM 3.5 dendrimer can bind 38+/-9 cadmium ions
      with Kb=1.3+/-0.13 x 10(3). The calculated Stern-Volmer constants of albumin
      fluorescence quenching by Cd2+, G3.5 and the "PAMAM G3.5-Cd2+" complex were 2.2+/
      0.2, 1.6+/-0.3 and 1.4+/-0.1(mmol/l)(-1), respectively. The data from the
      fluorescence and zeta-potential studies show that the "PAMAM G3.5-Cd2+" complex
      interacted much less strongly with human serum albumin than the pure dendrimer or
      Cd2+.

PMID- 19108998
TI  - A novel nanoporous gold modified electrode for the selective determination of
      dopamine in the presence of ascorbic acid.
AB  - The electrochemical detection of dopamine (DA) at conventional solid electrodes
      was interfered by the coexisted ascorbic acid (AA). To circumvent this problem,
      many modified electrodes were tried. In this paper, an attempt was made to use
      nanoporous gold (NPG) as modifying materials. The NPGs with different pore sizes
      were prepared simply by dealloying Ag from Au/Ag alloy with concentrated nitric
      acid. The glassy carbon electrode (GCE) based modified electrode was fabricated
      by simply affixing the NPG film on the surface of a GCE. The electrochemical
      behaviors of AA and DA at the modified electrode were studied. The results
      indicated that the NPG/GCE exhibited substantial enhancement in electrochemical
      sensitivity for DA and AA due to its large surface area. Results also showed that
      the oxidation of AA at the electrode was a diffusion-controlled process, but for
      DA it was an adsorption-controlled process. This result, together with the
      different anodic peak potentials of the two species, made it possible the
      selective determination of DA in the presence of AA. Due to the interaction of
      the amino group of DA with the surface of nanoscale gold, DA could be accumulated
      on the NPG/GCE, while AA could not. This permitted the coexistence of large
      amount of AA. When differential pulse voltammetry (DPV) was used, a submicrolevel
      of DA could be detected in the millimolar level of AA with a detection limit of
      17nM at a signal-to-noise ratio of 3. In a word, the modified electrode showed
      good sensitivity, selectivity and reproducibility.

PMID- 19108999
TI  - ROS scavenging capacity and neuroprotective effect of alpha-mangostin against 3
      nitropropionic acid in cerebellar granule neurons.
AB  - Alpha-mangostin is a xanthone with antioxidant properties isolated from
      mangosteen fruit. The reactive oxygen species (ROS) scavenging capacity and the
      potential protective effect of alpha-mangostin against the mitochondrial toxin 3
      nitropropionic acid (3-NP) in primary cultures of cerebellar granule neurons
      (CGNs) were studied in the present work. It was found that alpha-mangostin was
      able to scavenge in a concentration-dependent way singlet oxygen, superoxide
      anion and peroxynitrite anion. In contrast, alpha-mangostin was unable to
      scavenge hydroxyl radicals and hydrogen peroxide. Furthermore, alpha-mangostin
      was able to ameliorate in a concentration-dependent way the neuronal death
      induced by 3-NP. This protective effect was associated with an amelioration of 3
      NP-induced reactive oxygen species formation. It is concluded that alpha
      mangostin is able to scavenge directly several ROS and has a neuroprotective
      effect against 3-NP in primary cultures of CGNs, which is associated with its
      ability to ameliorate 3-NP-induced ROS production.

PMID- 19109000
TI  - Novel hypoglycemic effects of Ganoderma lucidum water-extract in obese/diabetic
      (+db/+db) mice.
AB  - In this study, we evaluated the pharmacological effects of Ganoderma lucidum (G.
      lucidum) (water-extract) (0.003, 0.03 and 0.3g/kg, 4-week oral gavage)
      consumption using the lean (+db/+m) and the obese/diabetic (+db/+db) mice.
      Different physiological parameters (plasma glucose and insulin levels,
      lipoproteins-cholesterol levels, phosphoenolpyruvate carboxykinase (PEPCK), 3
      hydroxy-3-methylglutaryl coenzyme A reductase (HMG CoA reductase) and isolated
      aorta relaxation of both species were measured and compared. G. lucidum (0.03 and
      0.3g/kg) lowered the serum glucose level in +db/+db mice after the first week of
      treatment whereas a reduction was observed in +db/+m mice only fed with 0.3g/kg
      of G. lucidum at the fourth week. A higher hepatic PEPCK gene expression was
      found in +db/+db mice. G. lucidum (0.03 and 0.3g/kg) markedly reduced the PEPCK
      expression in +db/+db mice whereas the expression of PEPCK was attenuated in
      +db/+m mice (0.3g/kg G. lucidum). HMG CoA reductase protein expression (in both
      hepatic and extra-hepatic organs) and the serum insulin level were not altered by
      G. lucidum. These data demonstrate that G. lucidum consumption can provide
      beneficial effects in treating type 2 diabetes mellitus (T2DM) by lowering the
      serum glucose levels through the suppression of the hepatic PEPCK gene
      expression.

PMID- 19109002
TI  - Understanding the social determinants of behaviours: can new methods help?

PMID- 19109001
TI  - Treatment of oral thrush in HIV/AIDS patients with lemon juice and lemon grass
      (Cymbopogon citratus) and gentian violet.
AB  - PURPOSE: The purpose of the study was to investigate the safety and efficacy of
      lemon juice and lemon grass (Cymbopogon citratus) in the treatment of oral thrush
      in HIV/AIDS patients when compared with the control group using gentian violet
      aqueous solution 0.5%. Oral thrush is a frequent complication of HIV infection.
      In the Moretele Hospice, due to financial constraints, the treatment routinely
      given to patients with oral thrush is either lemon juice directly into the mouth
      or a lemon grass infusion made from lemon grass (Cymbopogon citratus) grown and
      dried at the hospice. These two remedies have been found to be very efficacious
      therefore are used extensively. Gentian violet, the first line medication for
      oral thrush in South Africa, is not preferred by the primary health clinic
      patients due to the visible purple stain which leads them to being stigmatized as
      HIV-positive. Cymbopogon citratus and Citrus limon have known antifungal
      properties. METHODS: The study design was a randomised controlled trial. Ninety
      patients were randomly assigned to one of three groups: gentian violet, lemon
      juice or lemon grass. Inclusion criteria included being HIV-positive with a
      diagnosis of oral thrush. The study period was 11 days and patients were followed
      up every second day. International ethical principles were adhered to during the
      study. RESULTS: Of the 90 patients, 83 completed the study. In the intention-to
      treat analysis, none of the p-values were significant therefore the null
      hypothesis could not be rejected. In the analysis of the participants who
      actually completed the trial, the lemon juice showed better results than the
      gentian violet aqueous solution 0.5% in the treatment of oral thrush in an HIV
      positive population (p<0.02). The null hypothesis in terms of the lemon grass and
      gentian violet could also be rejected on the basis of the Chi-square test and the
      likelihood ratio test (p<0.05). CONCLUSIONS: Though the patient population was
      small, the use of lemon juice and lemon grass for the treatment of oral
      candidiasis in an HIV population was validated by the randomised controlled
      trial.

PMID- 19109003
TI  - Flow-injection electrochemical immunosensor for the detection of human IgG based
      on glucose oxidase-derivated biomimetic interface.
AB  - A newly flow-through electrochemical immunosensor for monitoring IgG in human
      serum has been developed by using core-shell SiO(2)/Au nanocomposites and
      poly(amidoamine) G4 dendrimer as matrices. The ferrocenecarboaldehyde-labeled
      anti-IgG biomolecules were initially chemisorbed onto the nanoparticle surface,
      and then glucose oxidase (GOx), as a blocking reagent instead of bovine serum
      albumin (BSA), was backfilled onto the modified surface. The formation of the
      antibody-antigen complex by a simple one-step immunoreaction between the
      immobilized anti-IgG and IgG in sample solution introduced a barrier of direct
      electrical communication between the immobilized GOx and the base surface, and
      decreased the immobilized GOx toward the catalytic oxidation of glucose. The
      performance and factors influencing the performance of the immunosensor were
      evaluated. Under optimal conditions, the linear range of the developed
      immunosensor by using GOx as enhancer was from 5.0 x 10(-6) to 9.6 x 10(-4)mol/L
      with a detection limit of 8.0 x 10(-7)mol/L IgG (at 3delta), while the detection
      limit by using BSA was 1.5 x 10(-5)mol/L IgG (at 3delta) with the linear range
      from 3.5 x 10(-5) to 1.2 x 10(-3)mol/L. The selectivity, reproducibility and
      stability of the proposed immunosensor were acceptable. The IgG contents in 37
      human serum samples obtained by the proposed method are identical with the data
      of clinical laboratory.

PMID- 19109004
TI  - Compact and low-cost biosensor based on novel approach to spectroscopy of surface
      plasmons.
AB  - A high-performance surface plasmon resonance (SPR) sensor based on a novel
      approach to spectroscopy of surface plasmons is reported. This approach employs a
      special diffraction grating structure (referred to as surface plasmon resonance
      coupler and disperser, SPRCD) which simultaneously couples light into a surface
      plasmon and disperses the diffracted light for spectral readout of SPR signal.
      The developed SPRCD sensor consists of a miniature cartridge integrating the
      diffraction grating and microfluidics and a compact optical system which
      simultaneously acquires data from four independent sensing channels in the
      cartridge. It is demonstrated that the SPRCD sensor is able to measure bulk
      refractive index changes as small as 3 x 10(-7) RIU (refractive index units) and
      to detect short oligonucleotides in concentrations down to 200 pM.

PMID- 19109005
TI  - Hydrogen peroxide biosensor based on the direct electrochemistry of myoglobin
      immobilized on silver nanoparticles doped carbon nanotubes film.
AB  - A novel H(2)O(2) biosensor has been fabricated based on the direct
      electrochemistry and electrocatalysis of myoglobin (Mb) immobilized on silver
      nanoparticles doped carbon nanotubes film with hybrid sol-gel techniques. A pair
      of redox peaks with peak separation of 160 mV and formal potential of -0.295V was
      observed at this composite film, corresponding to the direct electrochemistry of
      Mb. The heterogeneous rate constant was estimated to be 0.41s(-1). Under optimum
      conditions, the amperometric determination of H(2)O(2) was performed with a
      linear range of 2.0 x 10(-6)-1.2 x 10(-3)molL(-1) and a detection limit of 3.6 x
      10(-7)mol/L (S/N=3). The Michealis-Menten constant was also estimated to be
      1.62mmolL(-1). The proposed biosensor showed favorable reproducibility,
      stability, selectivity and accuracy, and has been used to determine H(2)O(2) in
      real samples with favorable recoveries.

PMID- 19109006
TI  - Kinetic insight into the mechanism of cholinesterasterase inhibition by aflatoxin
      B1 to develop biosensors.
AB  - In this paper, the inhibition effect of aflatoxin B1 on different species of
      cholinesterases was investigated to unravel action mechanism. The inhibition
      curves of several cholinesterase mutants (obtained by spectrophotometric
      measurements of enzyme activity, pS curves) were analyzed. They showed that this
      toxin reversibly inhibits cholinesterases by binding to a peripheral site located
      at the entrance of the active site gorge without entering inside the site.
      Electric eel enzyme revealed the highest inhibition extent with a binding
      constant estimated to 0.35 microM. This binding prevents the entrance of
      substrate en route to the catalytic site and also decreases chemical steps of the
      reaction at the catalytic site: acetylation is reduced to the half and
      deacetylation is reduced to the third. Electric eel acetylcholinesterase was used
      to settle an amperometric biosensor. The best detection was obtained by using 0.3
      mU enzyme on the electrode and 0.5mM ATCh in the solution. The limit of detection
      was 3 microM corresponding to 20% inhibition.

PMID- 19109007
TI  - Sensor materials for the detection of proteases.
AB  - The concept of generic and tunable sensor materials for the detection of
      proteases based on the thin film degradation of peptide cross-linked dextran
      hydrogels was explored. Hydrogel cross-links were formed via simple imine
      linkages between aldehyde groups in oxidized dextran and a peptide sequence
      susceptible to protease cleavage. Degradation of the hydrogel films was monitored
      in this study using a quartz crystal microbalance (QCM). The sensor material was
      developed using the protease/peptide pair of human neutrophil elastase (HNE) and
      Ala-Ala-Pro-Val-Ala-Ala-Lys (AAPVAAK). A direct relationship between the hydrogel
      degradation rate and protease activity was observed; HNE activities from 2.5 to
      30Uml(-1) were detected using 25% cross-linked films. Film degradation was rapid
      and was complete in less than 10min for HNE activities >/=10Uml(-1). An increase
      in the rate of degradation by a factor of 3.5 was achieved by increasing the
      cross-linking density from 25% to 75%. QCM admittance data fitted with a BVD
      equivalent circuit showed increases in film viscoelasticity upon enzyme addition.
      A second protease/peptide pair of cathepsin G and Ala-Ala-Pro-Phe-Phe-Lys
      (AAPFFK) was tested where 25% AAPFFK cross-linked hydrogels demonstrated a rapid
      response at 100mUml(-1). Swapping the protease/peptide pairs to HNE/AAPFFK and
      cathepsin G/AAPVAAK showed low levels of cross-sensitivity further demonstrating
      the specificity of film degradation.

PMID- 19109008
TI  - Genomes and evolution: multidimensional approaches to understanding diversity.

PMID- 19109010
TI  - Sono-chemical preparation of cellulose nanocrystals from lignocellulose derived
      materials.
AB  - This study examined the production of cellulose nanocrystals from
      microcrystalline wood cellulose, Avicel and recycled pulp of wood pulp using sono
      chemical-assisted hydrolysis. Two hydrolysis systems: deionized water and maleic
      acid were evaluated. In deionized water, Avicel produced cellulose nanocrystals
      with average diameter of 21+/-5 nm (minimum 15 nm and maximum 32 nm). Cellulose
      nanocrystals from recycled pulp were not distinctively spherical and had an
      average diameter of 23+/-4 nm (minimum 14 nm and maximum 32 nm). Maleic acid (50
      mM) sono-chemical assisted hydrolysis of Avicel at 15 degrees C and 90% power
      output for 9 min produced cellulose nanocrystals which were cylindrical in shape
      and were of dimensions, length 65+/-19 nm and width 15 nm.

PMID- 19109012
TI  - Pre-treatment of hospital wastewater by coagulation-flocculation and flotation.
AB  - Coagulation-flocculation and flotation processes were evaluated for the pre
      treatment of hospital wastewater, including the removal of 13 pharmaceutical and
      personal care products (PPCPs). Coagulation-flocculation assays were performed in
      a Jar-Test device and in a continuous pilot-scale plant. Raw hospital wastewater
      as well as the effluent from the continuous coagulation plant were treated in a
      flotation cell. Removal of total suspended solids (TSS) during pre-treatment was
      very effective, reaching an average removal efficiency of 92% in the combined
      coagulation-flotation process. Musk fragrances were eliminated to a high degree
      during batch coagulation-flocculation (tonalide: 83.4+/-14.3%; galaxolide: 79.2+/
      9.9%; celestolide: 77.7+/-16.8%), presumably due to their strong lipophilic
      character which promotes the interaction of these compounds with the lipid
      fraction of solids. For diclofenac (DCF), naproxen (NPX) and ibuprofen (IBP)
      maximum removals of 46%, 42% and 23%, respectively, were obtained, while the rest
      of PPCPs were not affected by the physico-chemical treatment. Flotation of raw
      wastewater led to slightly worse results compared to coagulation-flocculation,
      although the combined action of both improved the overall efficiency of the
      process. The proposed pre-treatment strategy for hospital wastewater is useful
      for assimilating its conventional physico-chemical characteristics to that of
      municipal wastewater as well as for reducing the load of some PPCPs into the
      sewer system.

PMID- 19109011
TI  - Synthesis and degradation of poly-beta-hydroxybutyrate in a sequencing batch
      biofilm reactor.
AB  - The aim of this work was the study of poly-beta-hydroxybutyrate (PHB) formation
      and degradation in a sequencing batch biofilm reactor (SBBR). The SBBR was
      operated in cycles comprising three individual phases: mixed fill, aeration and
      draw. A synthetic substrate solution with acetate and ammonium was used. PHB was
      formed during the aeration phase immediately after acetate depletion, and was
      subsequently consumed for biomass growth, owing to the high oxygen concentration
      in the reactor. It was observed a combination of suspended and biofilm growth in
      the SBBR with predominance of the fixed form of biomass (506 Cmmol and 2102
      Cmmol, respectively). Maximum PHB fraction of suspended biomass (0.13 Cmol/Cmol)
      was considerably higher than that of biofilm (0.01 Cmol/Cmol). This may possibly
      be explained by a combination of two factors: lower mass transfer limitation of
      acetate and higher fraction of heterotrophs in suspended biomass compared to the
      ones of biofilm.

PMID- 19109013
TI  - The application of a micro-algal/bacterial biofilter for the detoxification of
      copper and cadmium metal wastes.
AB  - In the present study the potential of a biofilter containing a mixture of dried
      micro-algal/bacterial biomass for removing heavy metals (Cu(2+), Cd(2+)) from
      dilute electroplating waste was tested. The biomass was produced in an artificial
      stream using the effluent of a municipal waste water treatment plant as a
      nutrient source, with the additional benefit of reducing phosphorus and nitrogen
      loadings. Baseline batch experiments determined that optimum adsorption for both
      metals (80-100%) were achieved with the deionized-H(2)O conditioned biomass at
      initial pH 4.0. Other biosorption variables (contact time, initial metal
      concentration) were also tested. Biosorption data were fitted successfully by the
      Langmuir model and results showed a high affinity of the used biomass for both
      metals (q(max) 18-31 mg metal/g.d.w). Flow-through column experiments containing
      Ca-alginate/biomass beads showed that metal adsorption depends also on flow-rate
      and volume of treated waste. Desorption of both metals with weak acids was very
      successful (95-100%) but the regeneration of the columns was not achieved due to
      the destabilization of beads.

PMID- 19109009
TI  - The advantage of women in cancer survival: an analysis of EUROCARE-4 data.
AB  - We analysed 1.6 million population-based EUROCARE-4 cancer cases (26 cancer
      sites, excluding sex-specific sites, and breast) from 23 countries to investigate
      the role of sex in cancer survival according to age at diagnosis, site, and
      European region. For 15 sites (salivary glands, head and neck, oesophagus,
      stomach, colon and rectum, pancreas, lung, pleura, bone, melanoma of skin,
      kidney, brain, thyroid, Hodgkin disease and non-Hodgkin's lymphoma) age- and
      region-adjusted relative survival was significantly higher in women than men. By
      multivariable analysis, women had significantly lower relative excess risk (RER)
      of death for the sites listed above plus multiple myeloma. Women significantly
      had higher RER of death for biliary tract, bladder and leukaemia. For all cancers
      combined women had a significant 5% lower RER of death. Age at diagnosis was the
      main determinant of the women's advantage, which, however, decreased with
      increasing age, becoming negligible in the elderly, suggesting that sex hormone
      patterns may have a role in women's superior ability to cope with cancer.

PMID- 19109014
TI  - Synthesis and biological evaluation of 2-phenylquinolones targeted at Tat/TAR
      recognition.
AB  - Tat (transactivator of transcription) is a small HIV protein rich in arginines
      that interacts with a viral RNA structure called TAR (trans-activation responsive
      region). Tat-TAR interaction is essential for viral gene expression, replication
      and pathogenesis. Small molecules able to interfere with TAR and to compete for
      Tat binding possess antiviral activity due to inhibition of viral transcription
      and expression, thus impairing formation of infectious virions. We report here,
      the synthesis and biological evaluation of a new series of quinolone derivatives,
      namely 2-phenylquinolones, designed with the aim of interfering with the
      protein/RNA complex. These new derivatives are able to efficiently interfere with
      Tat/TAR complex in vitro depending on precise structural requirements as
      demonstrated by fluorescence quenching assay analysis.

PMID- 19109015
TI  - Discovery of pentacyclic compounds as potent inhibitors of hepatitis C virus NS5B
      RNA polymerase.
AB  - We report a new series of inhibitors for hepatitis C virus NS5B RNA polymerase
      containing a constrained pentacyclic scaffold. Our SAR studies led to the
      identification of hexahydroindolo[2,1-a]pyrrolo[3,2-d][2]benzazepines exposing
      basic groups. The compounds displayed a high activity in the enzyme assay and
      displayed good activity in the cell-based (replicon) assay in the presence of
      serum proteins.

PMID- 19109016
TI  - Quinazolin-2-ylamino-quinazolin-4-ols as novel non-nucleoside inhibitors of
      bacterial DNA polymerase III.
AB  - High throughput screening led to the discovery of a novel series of quinazolin-2
      ylamino-quinazolin-4-ols as a new class of DNA polymerase III inhibitors. The
      inhibition of chromosomal DNA replication results in bacterial cell death. The
      synthesis, structure-activity relationships and functional activity are
      described.

PMID- 19109017
TI  - (-)-Cercosporamide derivatives as novel antihyperglycemic agents.
AB  - In our exploratory campaign for an antihyperglycemic agent with a novel mechanism
      of action, (-)-Cercosporamide 1, which is known as an antifungal agent, showed a
      potent plasma glucose lowering effect in hyperglycemic KK/Ta mice. The trouble
      was that it was accompanied by a decrease in food intake and a loss of body
      weight. We synthesized some (-)-Cercosporamide derivatives and succeeded to
      separate these actions. N,O-ketal type derivatives, especially compound 10, had
      the most potent plasma glucose lowering effect without affecting the food
      consumption or body weight.

PMID- 19109018
TI  - Formation of diazoate intermediate upon nitrous acid and nitric oxide treatment
      of 2'-deoxyadenosine.
AB  - When 2'-deoxyadenosine was treated with HNO(2) or NO, a small amount of a
      previously unidentified product was formed. The product was also formed by the
      reaction of 2'-deoxyadenosine with isoamyl nitrite in tetrahydrofuran as a major
      product. The product was identified as a diazoate derivative of 2'
      deoxyadenosine, a reaction intermediate. At the initial stage of the HNO(2) or NO
      reaction, the concentration of the diazoate was greater than or comparable to 2'
      deoxyinosine, a deamination product of 2'-deoxyadenosine. The diazoate was fairly
      stable and decomposed with a half-life of 66h at pH 7.4 and 37 degrees C. These
      results suggest that the diazoate can be formed in cellular nucleosides or DNA
      with biologically relevant dose of HNO(2) and NO.

PMID- 19109020
TI  - Observational gait analysis in traumatic brain injury: accuracy of clinical
      judgment.
AB  - OBJECTIVE: To determine the accuracy of clinicians' visual observations of gait
      disorders following traumatic brain injury (TBI). METHODS: 30 ambulant
      participants (sample of convenience) receiving physiotherapy for mobility
      limitations following TBI and 25 age, height, weight and sex matched healthy
      unimpaired controls (HC) were recruited. Kinematic and ground reaction force data
      during gait were captured and video recordings were concurrently collected.
      Participants with TBI walked at self-selected speed whilst HCs walked at
      preferred speed as well as the mean TBI speed for comparison. 40 doctors,
      experienced physiotherapists, new graduate physiotherapists and novices were
      observers. Each viewed and rated 36 gait variables for a randomized sub-sample of
      10 participants with TBI. Observer inaccuracy was calculated for each gait
      variable. RESULTS: Overall the accuracy of observational gait analysis was low
      and there was considerable variability in observations between clinicians. For
      most kinematic variables, observer inaccuracy ranged from 30% to 50%. Although
      experienced observers were generally more accurate, average inter-item
      correlations were low, indicating that experience did not consistently improve
      the accuracy of visual observations. Observational plane, gait variable type, the
      joint or the segment had little effect on accuracy of observations. CONCLUSIONS:
      Observational gait analysis for adults with TBI has relatively low accuracy. Some
      of the gait abnormalities evident from quantitative gait analysis were not
      detected by observational gait analysis.

PMID- 19109019
TI  - Potent and selective adenosine A2A receptor antagonists: 1,2,4-Triazolo[1,5
      c]pyrimidines.
AB  - Antagonism of the adenosine A(2a) receptor offers great promise in the treatment
      of Parkinson's disease. In the course of exploring pyrazolo[4,3-e]-1,2,4
      triazolo[1,5-c]pyrimidine A(2A) antagonists, which led to clinical candidate SCH
      420814, we prepared 1,2,4-triazolo[1,5-c]pyrimidines with potent and selective
      (vs A(1)) A(2a) antagonist activity, including oral activity in the rat
      haloperidol-induced catalepsy model. Structure-activity relationships and plasma
      levels are described for this series.

PMID- 19109021
TI  - Four analogues of spiroleptosphol isolated from Leptosphaeria doliolum.
AB  - Spiroleptosphol B (2), spiroleptosphol C (3), norleptosphol C (4) and
      hydroleptosphol (5) were isolated from ascomycete Leptosphaeria doliolum.
      Detailed (1)H and (13)C NMR spectral analyses revealed these were structural
      analogues of spiroleptosphol (1) which we have recently isolated from the same
      fungi. Spiroleptosphol B (2) carried an unprecedent 5,3
      dioxatricyclo[4.4.0.1(1.4)]undecane framework in place of the spirobicyclo ring
      system of 1. Spiroleptosphol C (3) was a 17-(R)-hydroxy derivative of 1.
      Norleptosphol C (4) was deduced to be the monocyclic structure biosynthetically
      resulted by decarboxylation from 3. Although 5 gave broaden (1)H NMR spectrum, it
      was gradually transformed to 2 which suggested being a hydrolysate of 1.

PMID- 19109022
TI  - Novel naphthalimide-amino acid conjugates with flexible leucine moiety as side
      chain: design, synthesis and potential antitumor activity.
AB  - A series of novel naphthalimide derivatives with flexible leucine side chains
      were designed and synthesized. Their antitumor activities were evaluated against
      HeLa, A549, P388, HL-60, MCF-7, HCT-8 and A375 cancer cell lines in vitro. The
      preliminary results showed that most of the derivatives had moderate antitumor
      activities with the IC(50) values of 10(-6)-10(-5) M. More importantly, compounds
      8a-c exhibited exclusive antitumor activities against MCF-7 cell line. The
      interaction between compound 8b and BSA was also investigated. DNA binding
      experiments showed that these derivatives behaved as DNA intercalating agents.
      This work provided a novel class of naphthalimide-based lead compounds with
      exclusive antitumor activities against MCF-7 cell line for further optimization.

PMID- 19109024
TI  - Synthesis of novel 1,4-benzoxazin-3-one derivatives as inhibitors against
      tyrosine kinases.
AB  - We designed and synthesized a novel 1,4-benzoxazin-3-one derivative 4 which would
      have inhibitory activities against tyrosine kinases. They could be synthesized
      easily from various carboxylic acids 10 and commercially available amines using
      TFP resin without purification. In this article, we will report the design and
      synthesis of a novel 1,4-benzoxazin-3-one chemical library 4 and the inhibitory
      activities against KDR and ABL which are closely related to chronic diseases such
      as cancer.

PMID- 19109023
TI  - Development of an optimized activatable MMP-14 targeted SPECT imaging probe.
AB  - Matrix metalloproteinase-14 (MT1-MMP or MMP-14) is a membrane-associated protease
      implicated in a variety of tissue remodeling processes and a molecular hallmark
      of select metastatic cancers. The ability to detect MMP-14 in vivo would be
      useful in studying its role in pathologic processes and may potentially serve as
      a guide for the development of targeted molecular therapies. Four MMP-14 specific
      probes containing a positively charged cell penetrating peptide (CPP) d-arginine
      octamer (r(8)) linked with a MMP-14 peptide substrate and attenuating sequences
      with glutamate (8e, 4e) or glutamate-glycine (4eg and 4egg) repeating units were
      modeled using an AMBER force field method. The probe with 4egg attenuating
      sequence exhibited the highest CPP/attenuator interaction, predicting minimized
      cellular uptake until cleaved. The in vitro MMP-14-mediated cleavage studies
      using the human recombinant MMP-14 catalytic domain revealed an enhanced cleavage
      rate that directly correlated with the linearity of the embedded peptide
      substrate sequence. Successful cleavage and uptake of a technetium-99m labeled
      version of the optimal probe was demonstrated in MMP-14 transfected human breast
      cancer cells. Two-fold reduction of cellular uptake was found in the presence of
      a broad spectrum MMP inhibitor. The combination of computational chemistry,
      parallel synthesis and biochemical screening, therefore, shows promise as a set
      of tools for developing new radiolabeled probes that are sensitive to protease
      activity.

PMID- 19109025
TI  - A brief tour of myxobacterial secondary metabolism.
AB  - Myxobacteria are soil-dwelling, Gram-negative bacteria which are notable not only
      for their multi-cellular 'social' lifestyles, but for production of structurally
      diverse secondary metabolites with potential in clinical therapy. Here we briefly
      review the history of myxobacterial natural products research, provide an
      overview of their unique secondary metabolism, with an emphasis on assembly line
      biosynthesis of polyketide and non-ribosomal peptide metabolites, and look to the
      future of the field.

PMID- 19109026
TI  - Heat stress alters the expression of salt stress induced genes in smooth
      cordgrass (Spartina alterniflora L.).
AB  - To understand the tolerance mechanism associated with high temperature stress in
      a halophyte smooth cordgrass (Spartina alterniflora), a few selected salt-induced
      genes including transcription factors were studied for their transcript
      abundance. The mRNA analysis of eight genes and nine transcription factors known
      to be involved in various salt tolerance mechanisms revealed temporal and tissue
      dependent variation in their expression under high temperature stress.
      Differential response of genes under heat and salt stress (reported earlier)
      indicated different mode of action in the metabolic pathway in response to
      different environmental cues, and a few common genes responsive to multiple
      stresses showed temporal and tissue-dependent variation in their expression. This
      study demonstrates that S. alterniflora could be a potential source of candidate
      genes conferring tolerance against high temperature in addition to salt tolerance
      for crop improvement.

PMID- 19109027
TI  - Secondary infection of a pre-existing thoracic aortic aneurysm by iatrogenic
      oesophageal perforation with aorta-oesophageal fistula formation.
AB  - We report a case of iatrogenic perforation of the oesophagus, with subsequent
      infection of a pre-existing thoracic aortic aneurysm and development of an aorto
      oesophageal fistula resulting in life-threatening haemorrhage. This was
      successfully treated with endovascular aortic stent-graft using a Cook Zenith Tx2
      device. Follow-up CT scan 3 months later showed that the aneurysm sac is getting
      smaller, and patient had no further septic or haemorrhagic complications.
      However, we emphasise that even if initial endovascular management of aorto
      oesophageal fistula is successful, these patients often risk recurrent sepsis and
      therefore long-term clinical and radiological surveillance is mandatory.

PMID- 19109028
TI  - Pulmonary artery agenesis and Kommerell's diverticulum presenting with
      hemoptysis.
AB  - Unilateral pulmonary artery agenesis is a rare congenital anomaly that is
      commonly associated with additional cardiovascular abnormalities. We report a
      case of intrapulmonary hemorrhage and hemoptysis in a patient with left-sided
      pulmonary artery agenesis as well as the first description of this anomaly in a
      patient with a diverticulum of Kommerell. The patient was successfully treated by
      performing a left pneumonectomy.

PMID- 19109029
TI  - Left ventricular wall rupture: revisited and updated.

PMID- 19109030
TI  - Emergency treatment of the thoracic aorta: results in 113 consecutive acute
      patients (the Talent Thoracic Retrospective Registry).
AB  - BACKGROUND: Elective thoracic endovascular aortic repair in selected patients
      with suitable aortic anatomy is associated with low morbidity and mortality, and
      is gaining widespread acceptance. Its benefit in acute thoracic aorta diseases,
      however, has not yet been demonstrated in high-numbered studies. This report
      presents data of the Talent Thoracic Retrospective Registry (TTR) of all patients
      who underwent endovascular stent grafting for acute thoracic aorta pathology.
      METHODS: Between December 1996 and July 2004 data were collected regarding 113
      consecutive patients who underwent emergent endovascular stent grafting of the
      thoracic aorta using the Talent thoracic stent graft (Medtronic, Inc., Santa
      Rosa, California) in 7 European referral centers. Acute thoracic aorta pathology
      consisted of 41 (36.3 %) traumatic aortic injuries, 37 (32.7 %) Stanford type B
      dissections, 5 (4.4 %) intramural hematomas, 18 (15.9 %) thoracic aorta
      aneurysms, 4 (3.5 %) pseudoaneurysms and 8 (7.1 %) penetrating ulcers. RESULTS:
      In all patients the stent graft system could be introduced via the common femoral
      artery. Conversion to open surgical repair was necessary in 2 patients, one in
      the early phase due to persistent bleeding via backflow in the false lumen from a
      distal entry tear, and another patient in a late phase due to retrograde
      dissection. Intraoperative mortality was 1.8%, one patient suffered a massive
      myocardial infarction, and another died of tamponade secondary to retrograde
      dissection. Overall hospital mortality was 8.0% (9 patients). In only 2 of them,
      it was considered a stent graft procedure related death. New neurological
      symptoms were seen in 6.2% (7 patients), with complete recovery in 5 patients.
      Mean follow-up was 15 months (range 1-69 months). Late mortality was 8.7% (9
      patients). Only one late death was considered aorta related. Overall re
      intervention rate was 8.9% (n=10) and was mainly for type I endoleak or
      persistent false lumen perfusion. CONCLUSION: Sub-analysis of the Talent Thoracic
      Retrospective Registry for endovascular stent grafting of acute thoracic aorta
      pathology in over 100 consecutive patients demonstrated its feasibility, with low
      morbidity and acceptable low mortality rates.

PMID- 19109031
TI  - Surfactant pretreatment decreases long-term damage after ischemia-reperfusion
      injury of the lung.
AB  - OBJECTIVE: Lung ischemia-reperfusion injury (LIRI) is a risk factor for primary
      acute graft failure following lung transplantation. LIRI hereby contributes to
      morbidity and mortality after lung transplantation. We have previously shown that
      surfactant pretreatment ameliorates LIRI up to 1 week after reperfusion. However,
      the impact of surfactant pretreatment on long-term outcome following LIRI is
      unknown. Therefore, the objective of this study was to investigate the effect of
      surfactant pretreatment on long-term outcome following LIRI. METHODS: Male
      Sprague-Dawley rats (n=63) were randomized to receive intratracheally
      administered porcine surfactant (400mg/kg) or no pretreatment. One hour
      thereafter, animals underwent 120min of warm ischemia by clamping the bronchus,
      pulmonary artery and vein of the left lung. A third group was sham-operated; a
      fourth group served as unoperated controls. Animals were killed on day 30 or 90
      after surgery. Arterial oxygenation and lung compliance were determined. Broncho
      alveolar lavage fluid (BALf) was collected to assess surfactant function and
      alveolar protein. Leukocyte infiltration was determined by flowcytometry in BALf,
      lung tissue and thoracic lymph nodes. Lungs of three animals per group were used
      for histological assessment. RESULTS: Lung compliance was lower on day 30 and day
      90 after LIRI than in sham-operated controls (day 30 V(max) 6.1+/-2.1 vs 12.6+/
      1.3, day 90 6.9+/-3.0 vs 12.1+/-1.6; C(max) day 30 0.49+/-0.17 vs 1.08+/-0.21,
      day 90 0.67+/-0.31 vs 1.11+/-0.17). Furthermore, the number of CD45RA(+)
      lymphocytes in left lung tissue was decreased on day 90 compared to unoperated
      animals (230.633+/-96.770 vs 696.347+/-202.909) and the number of macrophages
      elevated in left BALf on day 90. HE slides of LIRI animals were scored as
      fibroproliferative with moderate atelectasis. Surfactant pretreatment improved
      lung compliance (V(max) day 30 11.7+/-1.8, day 90 11.1+/-1.2; C(max) day 30
      1.04+/-0.23, day 90 1.16+/-0.21) and normalized the number of CD45RA(+)
      lymphocytes (769.555+/-421.016) in left lung tissue. Furthermore lung
      architecture on HE slides was on return to normal. However, more CD5(+)CD4(+)
      lymphocytes on day 30 (754.788+/-97.269 vs 430.409+/-109.909) and more
      macrophages on day 90 (2.144.000+/-630.633 vs 867.454+/-383.220) were measured in
      pretreated lung tissue compared to LIRI animals. CONCLUSIONS: Severe LIRI caused
      extensive pulmonary injury up to 90 days postoperatively. Surfactant pretreatment
      normalized pulmonary function, but resulted in an increased number of
      CD5(+)CD4(+)-cells and macrophages in lung tissue.

PMID- 19109032
TI  - Fish bone induced aortic rupture treated with endovascular stent graft.

PMID- 19109033
TI  - Lobectomy for metachronous lung cancer after pneumonectomy.
AB  - Second primary non-small cell lung cancer (NSCLC) is a well-known disease in
      patients having undergone successful NSCLC resection. Surgery for patients with
      cancer in the residual lung after pneumonectomy should not be excluded
      automatically. However, surgery on a single residual lung is usually done by
      wedge resection or segmentectomy, whereas lobectomy remains somewhat exceptional.
      We report the cases of two right upper lobectomy patients, alive and doing well
      at 5- and 6-year follow-up, with a FEV1 equal to 36% and 35% of predicted value,
      respectively.

PMID- 19109035
TI  - Inflammatory demyelinating events following treatment with anti-tumor necrosis
      factor.
AB  - BACKGROUND: Tumor necrosis factor alpha (TNF-alpha) is an inflammatory cytokine
      involved in certain inflammatory diseases including multiple sclerosis (MS),
      rheumatoid arthritis (RA), and Crohn's disease. The anti-TNF-alpha treatments
      used for RA may be associated with inflammatory demyelinating events affecting
      the central nervous system and may possibly aggravate known MS. OBJECTIVE: We
      report here three new cases of inflammatory demyelinating events of the central
      nervous system following treatment with anti-TNF-alpha. RESULTS: The neurological
      symptoms appeared on average 5 months after initiation of the treatment. For all
      patients, the inflammatory process was confirmed by brain magnetic resonance
      imaging. The symptoms totally or partially regressed as soon as anti-TNF-alpha
      treatment was stopped except for one patient who developed clinically defined MS.
      CONCLUSIONS: Inflammatory demyelination of the central nervous system may be
      associated with the use of anti-TNF-alpha. Patients with rheumatoid arthritis
      treated with these treatments should benefit from a follow-up which includes
      brain MRI.

PMID- 19109034
TI  - Nampt: linking NAD biology, metabolism and cancer.
AB  - Nicotinamide phosphoribosyltransferase (Nampt) converts nicotinamide to
      nicotinamide mononucleotide (NMN), a key nicotinamide adenine dinucleotide (NAD)
      intermediate. Previously identified as a cytokine pre-B-cell colony-enhancing
      factor and controversially claimed as an insulin-mimetic hormone visfatin, Nampt
      has recently drawn much attention in several fields, including NAD biology,
      metabolism and inflammation. As a NAD biosynthetic enzyme, Nampt regulates the
      activity of NAD-consuming enzymes such as sirtuins and influences a variety of
      metabolic and stress responses. Nampt also plays an important part in regulating
      insulin secretion in pancreatic beta-cells. Nampt seems to have another function
      as an immunomodulatory cytokine and, therefore, has a role in inflammation. This
      review summarizes these various functional aspects of Nampt and discusses its
      potential roles in diseases, including type 2 diabetes and cancer.

PMID- 19109036
TI  - What is the structure of b(2) ions generated from doubly protonated tryptic
      peptides?
AB  - A recent statistical study (Savitski, M. M.; Falth, M.; Eva Fung, Y. M.; Adams,
      C. M.; Zubarev, R. A. J. Am. Soc. for Mass Spectrom.doi:
      10.1016/j.jasms.2008.08.003) of a large spectral database indicated that the
      product ion spectra of doubly protonated tryptic peptides fall into two distinct
      classes. The main factor distinguishing the two classes is the relative abundance
      of the y(N-2) fragment: for Class I spectra y(N-2) is the most abundant y
      fragment while for Class II other y ions dominate the corresponding spectra. To
      explain the dominance of y(N-2) for Class I spectra formation of a nontraditional
      b(2) ion with a diketopiperazine (6-membered cyclic peptide) rather than an
      oxazolone structure was proposed. Here we present evidence from tandem mass
      spectrometry, hydrogen/deuterium exchange, and density functional calculations
      that do not support this proposal. Namely, that CID of doubly protonated YIGSR,
      YGGFLR, and YIYGSFK produce Class I product ion spectra, yet the b(2) fragment is
      shown to have the traditional oxazolone structure.

PMID- 19109037
TI  - Laser ablation of liver metastases from colorectal cancer with MR thermometry: 5
      year survival.
AB  - PURPOSE: To determine technical success, technique effectiveness, complications,
      and survival after laser ablation of liver metastases from colorectal cancer.
      MATERIALS AND METHODS: Eighty-seven consecutive patients (65 men and 22 women;
      mean age, 62.8 years) with 180 liver metastases from colorectal carcinoma were
      included between 1998 and 2005. They underwent laser ablation with magnetic
      resonance (MR) thermometry in 170 sessions. Indications for laser ablation were
      locally unresectable tumors (16.1%), metastases in both liver lobes (34.5%), and
      refusal of surgery and/or general contraindications to surgery (49.4%). Technical
      success, technique effectiveness, and complication and survival rates were
      evaluated retrospectively. RESULTS: Technical success was achieved in 178 of 180
      sessions (99%). Follow-up after 24-48 hours demonstrated an effectiveness rate of
      85.6%. Local tumor progression rate was 10% after 6 months. Major complications
      included large pleural effusion, large subcapsular hematoma, abscess, large
      pneumothorax, pleuritis with fever, intrahepatic hemorrhage, and biloma. Mean
      survival from the time of diagnosis of the primary tumor was 50.6 months for all
      patients treated (95% CI, 44.9-56.3 months). Median survival time was 54 months
      and survival rates were 95.7% at 1 year, 86.2% at 2 years, 72.4% at 3 years,
      50.1% at 4 years, and 33.4% at 5 years. The mean survival time after the first
      treatment was 31.1 months (95% CI, 26.9-35.3 months). CONCLUSIONS: Laser ablation
      of liver metastases of colorectal cancer with MR thermometry appears safe and
      efficacious. Although the results are encouraging, direct comparison with other
      ablative modalities in a prospective clinical trial would be necessary to
      definitely show one modality is superior.

PMID- 19109038
TI  - Signal detection theory, the exclusion failure paradigm and weak consciousness-
      evidence for the access/phenomenal distinction?
AB  - Block [Block, N. (2005). Two neural correlates of consciousness. Trends in
      Cognitive Science, 9, 46-52] and Snodgrass (2006) claim that a signal detection
      theory (SDT) analysis of qualitative difference paradigms, in particular the
      exclusion failure paradigm, reveals cases of phenomenal consciousness without
      access consciousness. This claim is unwarranted on several grounds. First,
      partial cognitive access rather than a total lack of cognitive access can account
      for exclusion failure results. Second, Snodgrass's Objective Threshold/Strategic
      (OT/S) model of perception relies on a problematic 'enable' approach to
      perception that denies the possibility of intentional control of unconscious
      perception and any effect of following different task instructions on the
      presence/absence of phenomenal consciousness. Many of Block's purported examples
      of phenomenal consciousness without cognitive access also rely on this
      problematic approach. Third, qualitative difference paradigms may index only a
      subset of access consciousness. Thus, qualitative difference paradigms like
      exclusion failure cannot be used to isolate phenomenal consciousness, any attempt
      to do so still faces serious methodological problems.

PMID- 19109039
TI  - Spatial aspects of bodily self-consciousness.
AB  - Visual, somatosensory, and perspectival cues normally provide congruent
      information about where the self is experienced. Separating those cues by virtual
      reality techniques, recent studies found that self-location was systematically
      biased to where a visual-tactile event was seen. Here we developed a novel,
      repeatable and implicit measure of self-location to compare and extend previous
      protocols. We investigated illusory self-location and associated phenomenological
      aspects in a lying body position that facilitates clinically observed abnormal
      self-location (as on out-of-body experiences). The results confirm that the self
      is located to where touch is seen. This leads to either predictable lowering or
      elevation of self-localization, and the latter was accompanied by sensations of
      floating, as during out-of-body experiences. Using a novel measurement we show
      that the unitary and localized character of the self can be experimentally
      separated from both the origin of the visual perspective and the location of the
      seen body, which is compatible with clinical data.

PMID- 19109040
TI  - The anatomical distribution and antimicrobial susceptibility of yeast species
      isolated from healthy dogs.
AB  - The aim of this work was to identify the predominant yeast species present at
      different anatomical sites in healthy dogs and to determine their in vitro
      antimicrobial susceptibility using a broth microdilution assay. Samples were
      collected from the preputial, vaginal, oral and perianal mucosae and the isolates
      cultured were identified according to their morphological characteristics and
      biochemical profile. Malassezia pachydermatis was the most commonly isolated
      yeast, followed by Candida parapsilosis, Candida tropicalis, Candida albicans,
      Saccharomyces cerevisiae and Rhodotorula spp. Minimum inhibitory concentrations
      of the azole derivatives ketoconazole, itraconazole and fluconazole against
      Candida spp. were 0.03-16 microg/mL, 0.06 to >16 microg/mL and 0.5-64 microg/mL,
      respectively and Candida isolates were sensitive to caspofungin and amphotericin
      B. Although all isolates of M. pachydermatis were sensitive to itraconazole,
      fluconazole, ketoconazole and amphotericin B, they were found to be resistant to
      caspofungin. The study has highlighted that Candida spp., M. pachydermatis, S.
      cerevisiae and Rhodotorula spp. are part of the normal canine surface microbiota
      and some of these organisms exhibit in vitro resistance to commonly used
      antimicrobials.

PMID- 19109041
TI  - Histological and biomechanical effects of palatal sclerotherapy in the horse
      using sodium tetradecyl sulfate.
AB  - Palatal sclerotherapy using sodium tetradecyl sulfate has been suggested as a
      treatment for dorsal displacement of the soft palate in young Standardbred
      horses. The present study evaluated histological and biomechanical changes in the
      equine soft palate following trans-endoscopic treatment with a low dose of this
      compound. Two horses were euthanased and examined at 2 weeks and at 1, 2, 4 and 6
      months post-sclerotherapy, while two further horses served as untreated controls.
      The technique was easily performed in all cases without major complications. On
      histological examination there was no evidence of palatal necrosis, inflammation
      or fibrosis in any of the treated or control animals. There was no variation in
      the density of palatal connective tissue between individuals, and on
      biomechanical assessment no significant difference in the stiffness of the
      palatal tissue was found between treated and control horses at any time. The
      lower dose of sodium tetradecyl sulfate used in this study relative to previous
      reports, might explain the absence of tissue alterations. This method of
      sclerotherapy did not alter the morphology or biomechanical properties of normal
      equine soft palates.

PMID- 19109042
TI  - Predictive factors for the regression of canine transmissible venereal tumor
      during vincristine therapy.
AB  - Canine transmissible venereal tumor (CTVT) is a neoplasm transmitted by
      transplantation. Monochemotherapy with vincristine is considered to be effective,
      but treatment time until complete clinical remission may vary. The aim of this
      study was to determine which clinical data at diagnosis could predict the
      responsiveness of CTVT to vincristine chemotherapy. One hundred dogs with CTVT
      entered this prospective study. The animals were treated with vincristine sulfate
      (0.025 mg/kg) at weekly intervals until the tumor had macroscopically
      disappeared. The time to complete remission was recorded. A multivariate Cox
      regression model indicated that larger tumor mass, increased age and therapy
      during hot and rainy months were independent significant unfavorable predictive
      factors retarding remission, whereas sex, weight, status as owned dog or breed
      were of no predictive relevance. Further studies are necessary to investigate
      whether these results are due to changes in immunological response mechanisms in
      animals with a diminished immune surveillance, resulting in delays in tumor
      regression.

PMID- 19109043
TI  - Cluster headache in children--experience from a specialist headache clinic.
AB  - BACKGROUND: Cluster headache is a primary headache disorder with the distinct
      clinical features: unilaterality, extreme pain, cranial autonomic features and
      periodicity. The prevalence of the disorder is 0.1% in adults and with a male
      predominance. The age of onset is usually in the second and third decade of life
      but the onset in the first decade is recognised. We describe our experience of
      cluster headache in children and review the literature. We have attempted to
      define the clinical features of cluster headache in children as compared to
      adults, the role of clinical investigations, reliability of clinical diagnosis,
      effective treatment and management options. METHODS: A retrospective casenotes
      review was conducted on all children with suspected cluster headache seen in our
      centre from 2000 to 2005. Case ascertainment was conducted using International
      Headache Society guidelines, and by telephone interviews with the parents.
      RESULTS: Eleven children were identified, (seven male and four female). The
      median age of onset was 8.5 years (range 2-14). The median age at diagnosis was
      11.5 years (range 7-17). Eight children had episodic and 3 children had chronic
      cluster headaches. The average attack duration was 72 min. The commonest reported
      bout frequency was one per day. Several children had circadian and circumannual
      periodicity and most displayed the other features of the disorder, such as
      agitated movement and cranial autonomic activation. Oxygen, methysergide,
      verapamil, zolmitriptan and dihydroergotamine were the drugs which were effective
      in terminating the headache. Paracetamol, ibuprofen and paracetamol/codeine
      combinations were not. CONCLUSION: We describe our experience with cluster
      headache in eleven children who all presented before the age of 16.

PMID- 19109044
TI  - Magnetic resonance in systems with equivalent spin-1/2 nuclides. Part 3: Ket
      analysis and spectral intensities.
AB  - In earlier papers (Parts 1 and 2), featuring group-theoretical analysis, it was
      shown that the isotropic EPR spectra of free radical (S=1/2) species XL(n), where
      the n equivalent nuclei also have spin 1/2, have a more complicated form than
      disclosed by the usual (first-order) oversimplified analysis. Explicit solutions
      for n=3 (analytic, as well as computational) of the spin-hamiltonian matrix H(s)
      for the energies and spin states were obtained and given in Part 2, but are
      amplified herein, and differences in several important representations of H(s)
      are discussed. In the present work, we focus also on details of relative spectral
      intensities, some of which are not straightforward. Subtle asymmetry effects in
      relevant EPR spectra are demonstrated. The crucial factor here turns out to
      reside in the difference between field-swept and frequency-swept spectra, and
      hinges on the fact that H(s) for the two states involved in any transition
      depends on Zeeman-field B as a variable in field-swept spectra, but B is a
      constant in frequency-swept spectra. An experimental spectrum of the free radical
      CF(3) is used as a quantitative example.

PMID- 19109046
TI  - Degradation of Acid Blue 25 in aqueous media using 1700kHz ultrasonic
      irradiation: ultrasound/Fe(II) and ultrasound/H(2)O(2) combinations.
AB  - In this work, the sonolytic degradation of an anthraquinonic dye, C.I. Acid Blue
      25 (AB25), in aqueous phase using high frequency ultrasound waves (1700kHz) for
      an acoustic power of 14W was investigated. The sonochemical efficiency of the
      reactor was evaluated by potassium iodide dosimeter, Fricke reaction and hydrogen
      peroxide production yield. The three investigated methods clearly show the
      production of oxidizing species during sonication and well reflect the
      sonochemical effects of high frequency ultrasonic irradiation. The effect of
      operational conditions such as the initial AB25 concentration, solution
      temperature and pH on the degradation of AB25 was studied. Additionally, the
      influence of addition of salts on the degradation of dye was examined. The rate
      of AB25 degradation was dependent on initial dye concentration, pH and
      temperature. Addition of salts increased the degradation of dye. Experiments
      conducted using distilled and natural waters demonstrated that the degradation
      was more efficient in the natural water compared to distilled water. To increase
      the efficiency of AB25 degradation, experiments combining ultrasound with Fe(II)
      or H(2)O(2) were conducted. Fe(II) induced the dissociation of ultrasonically
      produced hydrogen peroxide, leading to additional OH radicals which enhance the
      degradation of dye. The combination of ultrasound with hydrogen peroxide looks to
      be a promising option to increase the generation of free radicals. The
      concentration of hydrogen peroxide plays a crucial role in deciding the extent of
      enhancement obtained for the combined process. The results of the present work
      indicate that ultrasound/H(2)O(2) and ultrasound/Fe(II) processes are efficient
      for the degradation of AB25 in aqueous solutions by high frequency ultrasonic
      irradiation.

PMID- 19109045
TI  - The effect of acute application of pegvisomant alone and in combination with
      octreotide on endogenous GH levels during a 6-h test in patients with acromegaly
      on constant pegvisomant treatment.
AB  - OBJECTIVE: Co-treatment with somatostatin analogues and growth hormone receptor
      antagonists in acromegaly might be a new treatment option abolishing the negative
      effects of monotherapy. Nevertheless, little is known about the acute effect of
      the combined treatment on endogenous GH and pegvisomant levels. DESIGN: Ten
      acromegalic patients on constant pegvisomant therapy were included. Two 6-h GH
      secretion profiles were performed once after pegvisomant alone (P), the other
      after an additional 100 microg octreotide sc injection (PO). After 180 min, all
      patients received a standardized light mixed meal. Endogenous serum GH and
      pegvisomant levels were measured by special in-house assays. In addition, insulin
      and glucose were measured. RESULTS: In the combined profile PO, a significant
      decrease of median endogenous GH was seen (p<0.01, median percentage decline
      75.2%, range 23.7-88.2), which was not seen in profile P. Seven of 10 patients
      had a decline >70% and might be seen as responders. After meal, endogenous GH
      significantly decreased only in profile P (p<0.01). Pegvisomant levels did not
      differ significantly between profiles and did not change significantly during the
      tests. After meal, glucose levels rose higher and later and insulin levels lower
      and later in profile PO than in profile P. CONCLUSION: During pegvisomant
      treatment, endogenous GH can be reduced significantly by acute application of a
      somatostatin analogue. Therefore, in acromegalic patients on pegvisomant therapy
      GH regulation due to somatostatin analogues seems to be preserved.

PMID- 19109047
TI  - Development of a multi-component fiber-reinforced composite implant for load
      sharing conditions.
AB  - Fiber-reinforced composites (FRC) have the potential for use as load-bearing
      orthopaedic implants if the high strength and elastic modulus of FRC implant can
      be matched with local requirements. This study tested the in vivo performance of
      novel FRC implants made of unidirectional glass fibers (E-glass fibers in Bis-GMA
      and TEGDMA polymeric matrix). The implant surface was covered with bioactive
      glass granules. Control implants were made of surface-roughened titanium. Stress
      shielding effects of the implants were predicted by finite element modelling
      (FEM). Surgical stabilization of bone metastasis in the subtrochanteric region of
      the femur was simulated in 12 rabbits. An oblong subtrochanteric defect of a
      standardized size (reducing the torsional strength of the bones approximately by
      66%) was created and an intramedullary implant made of titanium or the FRC
      composite was inserted. The contralateral femur served as the intact control. At
      12 weeks of healing, the femurs were harvested and analyzed by radiography,
      torsional testing, micro-CT imaging and hard tissue histology. The functional
      recovery was unremarkable in both groups, although the final analysis revealed
      two healed undisplaced peri-implant fractures in the group of FRC implants. FEM
      studies demonstrated differences in stress-shielding effects of the titanium and
      FRC implants, but the expected biological consequences did not become evident
      during the follow-up time of the animal study. Biomechanical testing of the
      retrieved femurs showed no significant differences between the groups. The
      torsional strength of the fixed bones had returned the level of contralateral
      intact femurs. Both implants showed ongrowth of intramedullary new bone. No
      adverse tissue reactions were observed. Based on these favorable results, a large
      scale EU-project (NewBone, www.hb.se/ih/polymer/newbone) has been launched for
      development of orthopaedic FRC implants.

PMID- 19109048
TI  - Deformation simulation of cells seeded on a collagen-GAG scaffold in a flow
      perfusion bioreactor using a sequential 3D CFD-elastostatics model.
AB  - Tissue-engineered bone shows promise in meeting the huge demand for bone grafts
      caused by up to 4 million bone replacement procedures per year, worldwide. State
      of-the-art bone tissue engineering strategies use flow perfusion bioreactors to
      apply biophysical stimuli to cells seeded on scaffolds and to grow tissue
      suitable for implantation into the patient's body. The aim of this study was to
      quantify the deformation of cells seeded on a collagen-GAG scaffold which was
      perfused by culture medium inside a flow perfusion bioreactor. Using a microCT
      scan of an unseeded collagen-GAG scaffold, a sequential 3D CFD-deformation model
      was developed. The wall shear stress and the hydrostatic wall pressure acting on
      the cells were computed through the use of a CFD simulation and fed into a linear
      elastostatics model in order to calculate the deformation of the cells. The model
      used numerically seeded cells of two common morphologies where cells are either
      attached flatly on the scaffold wall or bridging two struts of the scaffold. Our
      study showed that the displacement of the cells is primarily determined by the
      cell morphology. Although cells of both attachment profiles were subjected to the
      same mechanical load, cells bridging two struts experienced a deformation up to
      500 times higher than cells only attached to one strut. As the scaffold's pore
      size determines both the mechanical load and the type of attachment, the design
      of an optimal scaffold must take into account the interplay of these two features
      and requires a design process that optimizes both parameters at the same time.

PMID- 19109049
TI  - Assessment of tissue prolapse after balloon-expandable stenting: influence of
      stent cell geometry.
AB  - Restenosis is a re-narrowing or blockage of an artery at the same site where
      treatment, such as a balloon angioplasty or stent procedure, has already taken
      place. Several clinical trials have shown a significant reduction in the
      restenosis rates with endovascular stenting. The purpose of stenting is to
      maintain the arterial lumen open by a scaffolding action that provides radial
      support. However, stenting can cause a vascular injury during the deployment.
      Indeed, in-stent restenosis remains a major problem in percutaneous coronary
      intervention, requiring patients to undergo repeated procedures and surgery. The
      loading imposed by the deployment of the stent on the artery is involved in the
      restenosis process. Furthermore, it is well known that the stent design plays a
      role in the outcome of the stenting interventional procedure. This study compares
      the mechanical effects of the expansion of five different designs of balloon
      expandable stents in a coronary artery by means of numerical models based on the
      finite element method. An index for the evaluation of the tissue prolapse based
      on the expanded configuration reached by the stent cells is proposed. The effects
      of the balloon inflation and deflation are included in the present study. Wall
      stresses and tissue prolapse of the vessel wall within the stent cells are
      evaluated and compared among the different stent designs. Results show that the
      printed area does not predict prolapse, and that the proposed index (PI) does
      correlate with tissue prolapse.

PMID- 19109050
TI  - Leaf development: time to turn over a new leaf?
AB  - Molecular cloning of mutations affecting the morphology of plant leaves has
      proven to be useful for the causal analysis of leaf development. Studies of leaf
      mutants have produced a wealth of biologically meaningful information on the
      genes that participate in leaf initiation, leaf polarity specification and
      maintenance, and leaf expansion and maturation. The availability of collections
      of gene-indexed insertional mutants, automated platforms for high-throughput
      imaging, and new morphometry software is making genome-wide leaf phenomics
      possible and complements classical forward genetics approaches. Large-scale
      phenomic studies will further our understanding, among others, of two intriguing
      phenomena that recently reentered the leaf scenario. One is the unexpected
      relationship between translation and leaf dorsoventrality, recently confirmed by
      the severe abaxialization of double mutants involving loss-of-function alleles of
      the developmental selector genes AS1 and AS2 and some genes encoding ribosomal
      proteins. The second unexplained phenomenon is the compensatory cell enlargement
      experienced by some leaf mutants, in which a reduced cell number is compensated
      by their increased cell size compared with the wild type. This compensation
      suggests that cell cycling and cell enlargement are integrated in leaf primordia
      via cell-to-cell communication.

PMID- 19109051
TI  - Study of fluorescence quenching mechanism between quercetin and tyrosine-H(2)O(2)
      enzyme catalyzed product.
AB  - Because of catalysis of horseradish peroxidase, the tyrosine reacted with
      H(2)O(2) to form the product S which was a strong fluorescence substance. To the
      product S, the quercetin was acted as a quencher. The fluorescence quenching
      mechanism was studied by the measurement of fluorescence lifetime and based on
      the Stern-Volmer plot. The reaction mechanism, which was the static quenching
      process between quercetin and product S, was studied. The binding constant,
      K=4.03 x 10(5) L mol(-1) and the number of binding sites n=1.09, were obtained
      against this reaction. The thermodynamic parameters were estimated. The data,
      DeltaH=-75.68 kJ mol(-1), DeltaS=-147.9JK(-1) mol(-1) and DeltaG=-29.17 kJ mol(
      1) showed that the reaction was spontaneous and exothermic. What is more, both
      DeltaH and DeltaS were negative values indicated that van der Waals interaction
      and hydrogen bonding were the predominant intermolecular forces between quercetin
      and product S.

PMID- 19109052
TI  - A highly selective naked-eye colorimetric sensor for acetate ion based on 1,10
      phenanthroline-2,9-dicarboxyaldehyde-di-(p-substitutedphenyl-hydrazone).
AB  - A new and simple colorimetric sensor with high selectivity for acetate ion based
      on 1,10-phenanthroline-2,9-dicarboxyaldehyde-di-(p-substitutedphenylhydrazone)
      receptor 2 has been synthesized. The selectively binding ability of receptor 2 to
      acetate ion over other anions tested was demonstrated by UV-vis absorption
      spectroscopy in DMSO. Comparing with other anions studied, the UV-vis absorption
      spectrum in dimethyl sulfoxide shows significant response toward acetate ion with
      high selectivity, and meanwhile dramatic color change is observed from yellow to
      green in the presence of acetate ion (5 x 10(-6)mol/L). Little UV-vis absorption
      spectrum change has occurred when receptor 2 was titrated with other different
      guest (F(-), Cl(-), Br(-), I(-), H(2)PO(4)(-) and OH(-)). In addition, the (1)H
      NMR spectrum titration shows deprotonation of the receptor in the presence of
      acetate ion.

PMID- 19109054
TI  - Prolonged detection of viral DNA in blood following life-threatening chickenpox
      in an immunocompromised child.

PMID- 19109053
TI  - IR spectroscopy investigation using DFT analysis on the structure of P(1)
      phosphorus dendrimer built from octasubstituted metal-free phthalocyanine core.
AB  - The IR spectra of P(1) phosphorus dendrimer built from an octasubstituted metal
      free phthalocyanine core have been recorded in the region 4000-400cm(-1). Besides
      the phthalocyanine core, P(1) possess also eight C(6)H(4)-CHN-N(CH(3))-P(S) arms
      and terminal P-Cl groups. The optimized molecular geometry, frequency and
      intensity of the IR bands have been calculated using density functional theory
      (DFT). The P(1) molecules exist in a stable conformation with planar C(6)H(4)-CHN
      N(CH(3))- fragments and phthalocyanine core. The calculated geometrical
      parameters and harmonic vibrational frequencies are predicted in a good agreement
      with the experimental data. The experimental IR spectrum of P(1) dendrimer was
      interpreted by means of potential energy distributions. Relying on DFT
      calculations a complete vibrational assignment is proposed. The difference IR
      spectra of molecules built from the thiophosphoryl, cyclotriphosphazene, and
      phthalocyanine cores with the same repeated units and terminal groups were
      studied in order to undermine the role of the core functionality on the dendrimer
      architecture.

PMID- 19109055
TI  - Periodic leg movements during sleep and periodic limb movement disorder in
      patients presenting with unexplained insomnia.
AB  - OBJECTIVE: The aim of this study was to evaluate quantitatively the presence and
      the characteristics of periodic leg movements during sleep (PLMS) in a group of
      consecutive patients presenting with daytime impairment related to insomnia of
      unknown etiology and whose polysomnographic features differ from those of healthy
      individuals only for a significantly increased arousal index in NREM sleep.
      METHODS: We recruited 20 consecutive adult patients with insomnia according to
      the ICSD-2 criteria, 20 patients with RLS, and 12 age-matched normal controls.
      The time structure of their polysomnographically recorded leg movements during
      sleep was analyzed by means of an approach particularly able to consider their
      periodicity. RESULTS: A subgroup of 12 patients with a relatively high number of
      periodic LM activity was detected with a statistically based approach using two
      indexes: total LM index and Periodicity index. This subgroup had high PLMS index,
      Periodicity index was also high and PLMS showed a progressive decrease during the
      night, being highest in the first hours of sleep. The characteristics of PLMS
      were identical within this insomnia subgroup and RLS patients. CONCLUSIONS: PLMS
      was a common finding in our patients with insomnia and a detailed analysis of
      their periodicity revealed that a subgroup of these patients had to be finally
      diagnosed with Periodic Limb Movement Disorder. SIGNIFICANCE: Polysomnography
      with the subsequent analysis of PLMS periodicity is able to differentiate between
      insomnia patient subgroups.

PMID- 19109056
TI  - Feedback-related processes during a time-production task in young and older
      adults.
AB  - OBJECTIVE: We examined whether the age-related decline in the integrity of the
      mid-brain dopamine system plays a role in the adaptation of precisely timed motor
      responses by feedback information. METHODS: Participants performed a time
      production task with feedback given after each trial. They were encouraged to use
      the feedback for improving temporal response accuracy. Event-related potentials
      to the feedback were analyzed. RESULTS: Older participants performed poorer than
      the young. Overall, high response accuracy was more favoured following positive
      than negative feedback. Older participants performed even worse after negative
      feedback than the younger. The feedback-related negativity (FRN) was of lower
      amplitude for older vs. young participants. FRN amplitude correlated
      significantly with response accuracy only for the young group. CONCLUSIONS: The
      decreased response accuracy during time production of the older group may be
      related to a weakened fronto-striatal dopamine system and thus a reduced ability
      to use feedback information for improving temporal aspects of the motor response.
      SIGNIFICANCE: The study points to difficulties especially for older participants
      to process error feedback, and it underlines the importance of positive feedback
      in order to improve temporal response accuracy. Suggestions can be drawn for the
      design of feedback information especially for older adults in motor learning
      environments.

PMID- 19109057
TI  - Regional electroencephalogram (EEG) spectral power and hemispheric coherence in
      young adults born at extremely low birth weight.
AB  - OBJECTIVES: We examined the effects of extremely low birth weight (ELBW<1000 g)
      on adult brain functioning. METHODS: We measured baseline regional EEG spectral
      power and hemispheric coherence in a cohort of 154 (M age=23 years) non-impaired
      young adults who were born at ELBW (n=71; M birth weight=874 g, M gestation
      age=27.5 weeks) and in a control group of full-term adults born at normal birth
      weight (NBW; n=83). RESULTS: ELBW adults exhibited significantly more power in
      the low EEG frequency bands (delta and theta) and less in the high EEG frequency
      bands (alpha and beta) than the NBW adults. This relative difference in the
      amount of high to low-frequency power was especially salient in the frontal
      regions. ELBW adults also exhibited significantly more short-distance EEG
      coherence in the right hemisphere compared to the NBW adults. CONCLUSIONS: Our
      results suggest that even among ELBW survivors without impairments, adverse
      events early in life may result in subtle neurological abnormalities.
      SIGNIFICANCE: This study provides a unique EEG profile of young adult survivors
      of ELBW showing that maturational delays of the brain may persist into late
      adolescence and emerging adulthood.

PMID- 19109059
TI  - Quantification of the auditory startle reflex in children.
AB  - OBJECTIVE: To find an adequate tool to assess the auditory startle reflex (ASR)
      in children. METHODS: We investigated the effect of stimulus repetition, gender
      and age on several quantifications of the ASR. ASR's were elicited by eight
      consecutive auditory stimuli in 27 healthy children. Electromyographic activity
      of orbicularis oculi, masseter, sternocleidomastoid, deltoid, abductor pollicis
      brevis, quadriceps muscles and the sympathetic skin response were recorded. ASR
      parameters (response probability in % and magnitude in area-under-the-curve)
      were: (1) combined response of all six muscles (2) blink response. RESULTS:
      Response probabilities were 78% in orbicularis oculi (median latency 41 ms), 17%
      in sternocleidomastoid (median latency 66 ms), 10% in masseter (median latency 66
      ms) and lower in other muscles. The ASR combined response probability and the
      sympathetic skin response significantly decreased with the repetitive stimuli,
      but the blink response probability did not. The magnitude (area-under-the-curve)
      of both the blink response and the combined response did not decrease with the
      repetitive stimuli. There were no gender or age effects. CONCLUSION: As in
      adults, the blink response and the combined response of multiple muscles show
      different habituation patterns in children. SIGNIFICANCE: Investigation of
      multiple muscles seems appropriate to quantify the ASR in children.

PMID- 19109058
TI  - Electrophysiological evidence of functional integration between the language and
      motor systems in the brain: a study of the speech Bereitschaftspotential.
AB  - OBJECTIVE: We investigated whether the Bereitschaftspotential (BP), an event
      related potential believed to reflect motor planning, would be modulated by
      language-related parameters prior to speech. We anticipated that articulatory
      complexity would produce effects on the BP distribution similar to those
      demonstrated for complex limb movements. We also hypothesized that lexical
      semantic operations would independently impact the BP. METHODS: Eighteen
      participants performed 3 speech tasks designed to differentiate lexical semantic
      and articulatory contributions to the BP. EEG epochs were time-locked to the
      earliest source of speech movement per trial. Lip movements were assessed using
      EMG recordings. Doppler imaging was used to determine the onset of tongue
      movement during speech, providing a means of identification and elimination of
      potential artifact. RESULTS: Compared to simple repetition, complex articulations
      produced an anterior shift in the maximum midline BP. Tasks requiring lexical
      search and selection augmented these effects and independently elicited a left
      lateralized asymmetry in the frontal distribution. CONCLUSIONS: The findings
      indicate that the BP is significantly modulated by linguistic processing,
      suggesting that the premotor system might play a role in lexical access.
      SIGNIFICANCE: These novel findings support the notion that the motor systems may
      play a significant role in the formulation of language.

PMID- 19109060
TI  - Choice of multivariate autoregressive model order affecting real network
      functional connectivity estimate.
AB  - OBJECTIVE: A realistic simulation exploiting real cortical sources identified
      from non-invasive extra-cranial recordings in healthy subjects has been
      considered in order to select the most robust procedure for choosing the correct
      order of multivariate autoregressive (MVAR) models. Different signal-to-noise
      ratios filter settings and sampling rates were also tested on the estimate of
      functional connectivity among the network nodes, in simulated and real cases.
      METHODS: Starting from magnetoencephalographic recordings, cortical sources in
      primary sensorimotor areas of the hand were obtained by functional source
      separation (FSS). Different criteria for the choice of the model order were
      compared in the simulated network constructed through one of the FSS-extracted
      sources and its noise-added delayed copies. In two real cases, a validation of
      the model order (not known a priori) choice was obtained by comparing the time
      frequency properties as depicted by classical non-parametric and MVAR methods at
      rest, during isometric contraction (stationary states) and while dynamically
      responding to a sensory stimulation (transient state). For completeness, the
      whole set of MVAR functional connectivity measures was taken into account, to
      assess the most suitable for our network description. RESULTS: That the use of an
      incorrect model order distorts network functional connectivity estimate was
      documented both in the realistic simulation and in the two real cases. The
      Minimal Description Length and Schwartz Bayesian Criterion were selected as the
      most robust for MVAR model order choice. Partial directed coherence (PDC) was the
      most suitable method for time-frequency connectivity estimate in the simulated as
      well as in the real cases, both in stationary and transient states. Moreover, the
      results of MVAR-based connectivity estimate depend on filter setting in the real
      case. CONCLUSIONS: The most robust procedure for choosing the correct MVAR model
      order was provided. The adjunctive comparison of MVAR to classical methods is
      recommended to validate the choice in the real case. SIGNIFICANCE: Correct MVAR
      model order choice and band filtering play an important role for the correct
      network connectivity estimate.

PMID- 19109061
TI  - Neurophysiological mechanisms of conduction impairment of the auditory nerve
      during cerebellopontine angle surgery.
AB  - OBJECTIVE: Intraoperative auditory brainstem response (ABR)-monitoring is useful
      for hearing preservation in patients undergoing cerebellopontine angle surgery.
      Prolongation of the latency of wave V, for example, is observed under surgical
      stress such as cerebellar retraction. We analyzed intraoperative ABR findings to
      study the neurophysiological mechanism(s) underlying latency prolongation.
      METHODS: The ABR recorded during microvascular decompression surgery was studied
      in 18 patients with hemifacial spasm. We measured each trace of the ABR records,
      both the latency of each wave and some interpeak latencies. We also analyzed
      their waveforms especially in the early component, to assess changes during
      surgery. RESULTS: The latency of wave V varied with cerebellar retraction. The
      delayed latency of wave V was correlated with the prolonged interpeak latency of
      waves I-III. An additional wave (designated wave I') between waves I and II was
      appeared; it was accompanied by a prolongation in the latency of wave V. Wave I'
      contributed to prolongation of the interpeak latency of waves I-III, resulting in
      a delay in the latency of wave V. Chronological analysis revealed that the
      minimum latency of wave I' was the same as wave IN, suggesting that wave I' arose
      near the porus acusticus internus (PAI). CONCLUSION: Our study showed that
      cerebellar retraction may result in conduction impairment of the auditory nerve
      near the PAI, suggesting that the Obersteiner-Redlich zone is an
      electrophysiologically vulnerable site and wave I' is derived from the change in
      the vector of wave IN. SIGNIFICANCE: Our findings may provide neurophysiological
      evidence to support the theoretical model of ABR generators by Scherg and von
      Cramon.

PMID- 19109063
TI  - REM sleep behaviour disorder (RBD) and its associations in young patients.
AB  - STUDY OBJECTIVES: To retrospectively examine the characteristics of a population
      of patients <50 years of age with clinical and polysomnographic features
      diagnostic for RBD. METHODS: Review of our sleep centre's database for patients
      with RBD diagnosed over the last 7 years. Ninety-one patients were separated into
      two groups according to their age at the time of diagnosis (<50 y and 50 y).
      Clinical and polysomnographic data were reviewed. RESULTS: Sixty-two were male;
      mean age was 52+/-19 y. Thirty-nine were <50 y. In the group <50 y there was a
      male predominance but in a smaller proportion (M:F=1.4:1) compared with the group
      50 (M:F=3:1). Seventy-six patients complained of abnormal behaviour (AB) during
      sleep, 12 with narcolepsy complained of excessive daytime sleepiness (EDS) with
      the AB being elicited only during consultation, and three complained of both EDS
      and AB. All patients, except one in the group 50, described AB related to vivid
      dreams with violent content. The majority of the patients had the idiopathic form
      of RBD in both groups (51.2% group <50, 63.4% group 50). The secondary form was
      associated with narcolepsy in 38.4% of patients in the group <50 y and with a
      synucleinopathy in 28.8% of patients in the group 50. A strong association was
      noted between RBD and non-REM parasomnias. CONCLUSIONS: In a population of
      patients with RBD presenting to a regional sleep laboratory, more than one-third
      of patients were <50 y at time of diagnosis. The commonest associated disorder
      was narcolepsy in patients <50 y, and synucleinopathy in those 50 y. The
      coexistence of RBD with a NREM parasomnia was not uncommon in cases of idiopathic
      RBD affecting patients <50 y.

PMID- 19109065
TI  - Teasing apart drug treatments and individual symptoms in narcolepsy.

PMID- 19109064
TI  - Welcome to the club: substantial sleep dysfunction also in progressive
      supranuclear palsy.

PMID- 19109066
TI  - Blue in the face.

PMID- 19109067
TI  - Sleep disturbances in variant of Creutzfeldt-Jakob disease.

PMID- 19109068
TI  - Gene expression profiling of Yersinia pestis with deletion of lcrG, a known
      negative regulator for Yop secretion of type III secretion system.
AB  - Yersinia pestis injects a set of virulent proteins into the cytosol of eukaryotic
      cells by a type III secretion system (T3SS). LcrG is a known negative regulator
      for secretion of Yersinia outer-membrane proteins (Yops) by blocking the
      secretion apparatus (Ysc) from the inner membrane. To further understand the
      effect of lcrG deletion on Y. pestis T3SS regulation, transcriptional profiles
      from the DeltalcrG mutant and wild-type Y. pestis strains were compared. The
      results showed that although the DeltalcrG mutant was markedly attenuated (600
      fold increase of LD(50) in s.c. challenged BALB/c mice), transcriptions of almost
      all the type III genes were upregulated significantly in the DeltalcrG mutant.
      The immunoblotting analysis of YopM and LcrV demonstrated that their expressions
      were also increased in the DeltalcrG mutant in comparison to the wild-type
      strain. We speculate that, in addition to the negative regulation of the Yop
      secretion, LcrG could possibly play a negative regulatory role in the
      transcription of T3SS genes through indirect mechanisms. Furthermore, this report
      also revealed significant transcriptional changes in the genes encoding cell
      envelope-related proteins and a virulence-related transcription factor RovA in
      the DeltalcrG mutant.

PMID- 19109069
TI  - Pharmacological targets revealed by myocardial postconditioning.
AB  - Postconditioning is an intervention in which controlled, brief, intermittent
      periods of ischaemia at the onset of reperfusion protect myocardium from the
      lethal consequences of reperfusion ('reperfusion injury'). Postconditioning has
      been demonstrated in humans with acute myocardial infarction and offers the
      possibility of further limiting infarct size in patients undergoing reperfusion
      therapy. We review current research that focuses on the molecular mechanisms of
      postconditioning. The molecular pathways are incompletely mapped but they
      probably converge on suppression of mitochondrial permeability transition pore
      opening during early reperfusion, an event that is thought to promote cell death
      at reperfusion. A number of upstream signalling pathways, activated by autacoid
      factors, converge on this crucial target and these offer a range of realistic
      possibilities for pharmacological induction of a postconditioned state.

PMID- 19109070
TI  - Putative druggable targets for selective enhancement of cardiac conduction.
AB  - Putative druggable targets to selectively enhance cardiac conduction can be
      considered from the level of the ion channels determining the initiation and
      duration of the cardiac action potential to the gap junction proteins responsible
      for optimal cellular electrical coupling. Nature has provided a number of
      inherited disorders of conduction, the pathophysiology of which offer novel
      insights into future therapeutic targets. This review will focus upon the
      potential cellular and molecular targets for drug development based upon our
      knowledge of their pathophysiological impact.

PMID- 19109071
TI  - The role of hypercytokinemia in the pathophysiology of tumor lysis syndrome (TLS)
      and the treatment with continuous hemodiafiltration using a
      polymethylmethacrylate membrane hemofilter (PMMA-CHDF).
AB  - OBJECTIVE: To examine the role of hypercytokinemia in the pathophysiology of
      tumor lysis syndrome (TLS) and the efficacy of continuous hemodiafiltration in
      the treatment of TLS. DESIGN AND SETTING: Retrospective observational study in a
      general intensive care unit of a university hospital. PATIENTS: Four patients
      with hematological disorder developing TLS after the treatment of anti-tumor
      chemotherapy. INTERVENTIONS: Continuous hemodiafiltration using a
      polymethylmethacrylate membrane hemofilter (PMMA-CHDF) was performed at the onset
      of TLS. Blood samples were collected daily after ICU admission, and clinical
      parameters and blood levels of cytokines were evaluated. MEASUREMENTS AND
      RESULTS: All four patients underwent induction anti-tumor chemotherapy, during
      which they developed hyperuricemia, hyperkalemia, and acute renal failure. Two of
      them also developed multiple organ failure. Serum levels of tumor necrosis factor
      (TNF) -alpha, interleukin-6 (IL-6), and IL-10 prior to the initiation of PMMA
      CHDF were 102+/-85 pg/mL, 1097+/-546 pg/mL, and 98+/-83 pg/mL, respectively (mean
      +/- SD). After three days of PMMA-CHDF treatment, corresponding blood levels were
      37+/-55 pg/mL, 326+/-511pg/mL, and 9+/-8 pg/mL, respectively. Thus, all cytokine
      levels were significantly decreased by three days of PMMA-CHDF treatment (p<0.05,
      paired t-test). Following three days of PMMA-CHDF treatment, blood urea nitrogen
      (BUN) and serum creatinine (Cre.) were significantly decreased (pre/post BUN
      42.3+/-15.4/16.5+/-8.4 mg/dL, p<0.05, pre/post Cre. 2.7+/-1.2/1.2+/-0.6 mg/dL,
      mean +/- SD, p<0.05). Furthermore, the clinical condition of each patient was
      improved after the treatment of PMMA-CHDF, and all of four patients were
      survived. CONCLUSION: Hypercytokinemia plays a pivotal role in the
      pathophysiology of TLS and PMMA-CHDF may be an effective therapeutic modality for
      TLS patients not only as renal replacement therapy but also as a cytokine
      modulator.

PMID- 19109072
TI  - Appendix interposition for total left ureteral reconstruction.
AB  - INTRODUCTION: Appendix interposition has been described as an option for surgical
      reconstruction of partial and total ureteral defects both in children and adults.
      However, to our knowledge, appendix interposition for a total left ureteral
      reconstruction has never been described. CASE REPORT: We report the first case of
      total left ureteral reconstruction with cecal appendix to connect the renal
      pelvis of a native kidney to the urinary bladder in a 3-month-old child with
      ureteral necrosis following pyeloplasty. RESULTS: Postoperative recovery was
      uneventful. Postoperative intravenous pyelogram showed good flow of dye from the
      pelvis past the appendicular graft into the bladder. After 6 months, the child
      was asymptomatic, within the normal growth curve for height and weight.
      CONCLUSION: Total ureteral reconstruction with cecal appendix is a feasible
      technique in young children. Surveillance for late operative complications is
      required, since this is the first case of total left ureteral reconstruction with
      appendix to connect the renal pelvis of a native kidney to the urinary bladder.

PMID- 19109073
TI  - Using supported liquid extraction together with cellobiohydrolase chiral
      stationary phases-based liquid chromatography with tandem mass spectrometry for
      enantioselective determination of acebutolol and its active metabolite diacetolol
      in spiked human plasma.
AB  - A high through-put, sensitive, and enantioselective LC-MS/MS-based bioanalytical
      method was developed and validated for the simultaneous determination of
      individual acebutolol (AC) and its active metabolite-diacetolol (DC) enantiomers
      in human plasma using cellobiohydrolase (CBH) chiral stationary phases (CSP).
      Systematic optimization of chromatographic conditions including organic content,
      buffer concentration, and pH of mobile phases was conducted to improve the
      through-put for the direct separation of both AC and DC on CBH column during
      method development. Complete baseline separation of enantiomeric AC and DC was
      achieved within 1.5 min with a LC flow rate of 0.9 ml/min under method validation
      conditions. To further improve the assay through-put, supported liquid extraction
      (SLE) in a 96-well plate format was used for sample extraction. The method
      validation was conducted over the curve range of 0.0500-50.0 ng/ml for each AC
      and DC enantiomer using 0.100 ml of plasma sample. The intra- and inter-day
      precision and accuracy of the quality control samples at low, medium, and high
      concentration levels showed <or=4.5% relative standard deviation (R.S.D.) and 
      8.7 to 5.6% relative error (R.E.) for individual AC and DC enantiomers.

PMID- 19109074
TI  - Development and validation of a gas chromatography-negative chemical ionization
      tandem mass spectrometry method for the determination of ethyl glucuronide in
      hair and its application to forensic toxicology.
AB  - Ethyl glucuronide (EtG) is a minor and direct metabolite of ethanol. EtG is
      incorporated into the growing hair allowing retrospective investigation of
      chronic alcohol abuse. In this study, we report the development and the
      validation of a method using gas chromatography-negative chemical ionization
      tandem mass spectrometry (GC-NCI-MS/MS) for the quantification of EtG in hair.
      EtG was extracted from about 30 mg of hair by aqueous incubation and purified by
      solid-phase extraction (SPE) using mixed mode extraction cartridges followed by
      derivation with perfluoropentanoic anhydride (PFPA). The analysis was performed
      in the selected reaction monitoring (SRM) mode using the transitions m/z 347-
      >163 (for the quantification) and m/z 347-->119 (for the identification) for EtG,
      and m/z 352-->163 for EtG-d(5) used as internal standard. For validation, we
      prepared quality controls (QC) using hair samples taken post mortem from 2
      subjects with a known history of alcoholism. These samples were confirmed by a
      proficiency test with 7 participating laboratories. The assay linearity of EtG
      was confirmed over the range from 8.4 to 259.4 pg/mg hair, with a coefficient of
      determination (r(2)) above 0.999. The limit of detection (LOD) was estimated with
      3.0 pg/mg. The lower limit of quantification (LLOQ) of the method was fixed at
      8.4 pg/mg. Repeatability and intermediate precision (relative standard deviation,
      RSD%), tested at 4 QC levels, were less than 13.2%. The analytical method was
      applied to several hair samples obtained from autopsy cases with a history of
      alcoholism and/or lesions caused by alcohol. EtG concentrations in hair ranged
      from 60 to 820 pg/mg hair.

PMID- 19109075
TI  - Extraction of trypsin from bovine pancreas by applying polyethyleneglycol/sodium
      citrate aqueous two-phase systems.
AB  - The goal of this work was to determine the optimal conditions for separating
      trypsin (TRP) from alpha-chymotrypsin (ChTRP) and to apply them for trypsin
      purification from bovine pancreas by liquid-liquid extraction with
      polyethyleneglycol/sodium citrate (PEG/NaCit) aqueous two-phase systems.
      Partitioning behaviours of TRP and ChTRP are demonstrated to be very sensitive to
      variables such as PEG molecular weight, pH and tie line length. Aqueous two-phase
      systems (ATPSs) formed by PEG of MW 3350 and NaCit pH 5.20 showed the best
      separation capability. The addition of NaCl up to a final concentration of 7%
      (w/w) and the decrease of top/bottom volume ratio to 0.1 led to the recovery of
      60% of pancreatic TRP in a concentrated form in the top phase with a 3-fold
      purification. Biomass presence up to 25% (w/w) of the total system mass did not
      affect significantly yield and purification parameters.

PMID- 19109076
TI  - Determination of terbutaline sulfate by capillary electrophoresis with
      chemiluminescence detection.
AB  - A novel capillary electrophoresis (CE) with chemiluminescence (CL) detection
      method for determination of terbutaline sulfate has been developed. This method
      is based on the chemiluminescence reaction of potassium ferricyanide with luminol
      in sodium hydroxide medium sensitized by terbutaline sulfate. With the peak
      height as a quantitative parameter applying optimum working conditions,
      terbutaline sulfate is determined over the range of 7.0 x 10(-8) to 3.6 x 10(-6)M
      with a detection limit of 3.0 x 10(-8)M. The relative standard deviation (RSD)
      was 4.6% for 6.0 x 10(-7)M terbutaline sulfate (n=11). The proposed method has
      been applied to determination of terbutaline sulfate in commercial terbutaline
      sulfate drug and spiked in human urine with satisfactory results.

PMID- 19109077
TI  - Suitability of different polymer bags for storage of volatile sulphur compounds
      relevant to breath analysis.
AB  - Suitability of five polymer sampling containers (Nalophan, transparent Tedlar,
      black layered Tedlar, Teflon and FlexFoil) for sampling and storage of six
      relevant to breath analysis volatile sulphur compounds: H(2)S, MeSH, EtSH, COS,
      DMS and CS(2) was studied using solid phase microextraction (SPME) and gas
      chromatography coupled with mass spectrometry (GC-MS). Investigations were made
      with respect to the several factors like: recovery, background, influence of
      light, ageing effect and matrix effects. Additionally, the optimal reusability
      conditions were established. Findings suggest analyzing the breath VSCs within 6h
      after sampling. Flexfoil bags were found to be the best choice for the VSCs
      storage up to 24h (recovery about 90% with the exception of DMS). For shorter
      storing times (6-8h) transparent Tedlar is a good alternative for Flexfoil
      (losses up to 10%).

PMID- 19109078
TI  - Analysis of second-generation antidepressant drug, sertraline and its active
      metabolite, N-desmethyl sertraline in human plasma by a sensitive and selective
      liquid chromatography-tandem mass spectrometry method.
AB  - A precise, sensitive and high throughput liquid chromatography-tandem mass
      spectrometry (LC-MS/MS) method for simultaneous determination of sertraline (SER)
      and its primary metabolite, N-desmethyl sertraline (NDS) in human plasma is
      developed and validated. The analytes and the internal standard-fluoxetine were
      extracted from 300 microL aliquots of human plasma via liquid-liquid extraction
      in methyl tert-butyl ether. Chromatographic separation was achieved in a run time
      of 2.5 min on a Betasil C8 column (100 mm x 2 .1 mm, 5 microm) under isocratic
      conditions. Detection of analytes and IS was done by tandem mass spectrometry,
      operating in positive ion and multiple reaction monitoring (MRM) acquisition
      mode. The protonated precursor to product ion transitions monitored for SER, NDS
      and IS were m/z 306.2-->159.0, 292.1-->159.0 and 310.6-->148.4, respectively. The
      method was fully validated for its sensitivity, selectivity, linearity, accuracy
      and precision, matrix effect, stability study and dilution integrity. A linear
      dynamic range of 0.5-150 ng/mL was established for both the analytes with mean
      correlation coefficient (r) of 0.9993 and 0.9980, respectively. The intra-batch
      and inter-batch precision (%CV) across five quality control levels was <or=10.4%
      for both the analytes. The method was successfully applied to a bioequivalence
      study of 100mg sertraline tablet formulation in 32 healthy Indian male subjects
      under fasting condition.

PMID- 19109079
TI  - A rapid and sensitive LC/MS/MS assay for the quantitation of brimonidine in
      ocular fluids and tissues.
AB  - We report here the development and validation of an LC/MS/MS method for the rapid
      and accurate quantitation of brimonidine in ocular tissues and fluids using
      brimonidine-d(4) as an internal standard (IS). Brimonidine was extracted from
      retina, iris/ciliary body, and vitreous humor samples with an acetonitrile:water
      (1:1) solution followed by sonication and vortexing. Aliquots of aqueous humor,
      iris/ciliary body, retina, and vitreous humor samples were diluted with
      acetonitrile containing IS and were separated on a reverse-phase HPLC column
      under isocratic conditions. Brimonidine (m/z transition: 292-->212) and the
      internal standard (m/z transition: 296-->216) were analyzed via multiple-reaction
      monitoring (MRM) in the positive electrospray mode on a 4000 Q TRAP instrument.
      The total analysis time for each sample was less than 2.0 min. The calibration
      curves for brimonidine (1-1000 ng/mL) were constructed using a linear regression
      with 1/x(2) weighing. The lower limit of quantitation for brimonidine was 1.0
      ng/mL for aqueous humor, 10 ng/g for iris/ciliary body, 12.5 ng/g for retina, and
      1.6 ng/g for vitreous humor. Intra-day and inter-day estimates of accuracy and
      precision were within 15% of their nominal values indicating that the method is
      reliable for quantitation of brimonidine in ocular tissues and fluids.

PMID- 19109080
TI  - Determination of hair nicotine by gas chromatography-mass spectrometry.
AB  - Hair nicotine is a known biomarker for monitoring long-term environmental tobacco
      smoke (ETS) exposure and smoking status. In general, hair nicotine assay involves
      alkaline digestion, extraction and instrumental analysis. The gas chromatography
      mass spectrometry (GC-MS) assay currently developed has shown to be of high
      throughput with average approximately 100 hair samples being extracted and
      analyzed per day. This was achieved through simplified extraction procedure and
      shortened GC analysis time. The extraction was improved by using small volume
      (0.4 mL) of organic solvent that does not require further evaporation and salting
      steps prior to GC-MS analysis. Furthermore, the amount of hair utilized in the
      extraction was very little (5 mg) while the sensitivity and selectivity of the
      assay is equal, if not better than other established methods. The linearity of
      the assay (r(2)>0.995), limit of quantitation (0.04 ng/mg hair), within- and
      between-assays accuracies and precisions (<11.4%) and mean recovery (92.6%) were
      within the acceptable range.

PMID- 19109081
TI  - Identification of biomarkers indicating cellular changes after treatment of
      neuronal cells with the C3 exoenzyme from Clostridium botulinum using the iTRAQ
      protocol and LC-MS/MS analysis.
AB  - Proteomic approaches are used to identify biomarkers, to monitor pathological
      changes inside of cells and for a better diseases diagnosis. Comparable changes
      in protein homeostasis also occur in differentiating cells and proteomic
      techniques should be suitable to identify biomarkers that indicate different
      steps of cellular development. The C3 exoenzyme from Clostridium botulinum
      (C3bot) inactivates Rho GTPases and induces morphological cellular changes like
      cell rounding and neurite outgrowth [G. Ahnert-Hilger, M. Holtje, G. Grosse, G.
      Pickert, C. Mucke, B. Nixdorf-Bergweiler, P. Boquet, F. Hofmann, I. Just, J.
      Neurochem. 90 (2004) 9]. To investigate these observations further a comparative
      proteomic approach has been chosen to elucidate C3bot effects in the
      neuroblastoma cell line model SH-SY5Y. The screening method applied for biomarker
      detection was based on the stable isotope approach isobaric tagging for relative
      and absolute quantification (iTRAQ). Proteins of C3bot-treated and untreated
      cells were digested and peptides were labeled by the iTRAQ reagent, combined, and
      separated by means of a two-dimensional nano-HPLC system. Peptide analysis was
      performed in a MALDI-TOF/TOF mass spectrometer. Identification and quantification
      of peptides and their corresponding proteins were accomplished by MS/MS spectra
      analysis. Overall, five replicate measurements identified 355 different proteins
      of which 235 were accessible for quantification. C3bot altered the concentration
      of 55 proteins (at least 1.3-fold) and several proteins were identified as
      possible biomarker candidates that indicate C3bot-induced cellular changes.

PMID- 19109082
TI  - Differential effects of exogenous and endogenous hyaluronan on contraction and
      strength of collagen gels.
AB  - The addition of exogenous hyaluronan to biomaterial scaffolds has been an
      important area of investigation for many decades. The ability to manipulate
      endogenous production of hyaluronan via the hyaluronan syntheses has offered
      another mechanism to study the effect of hyaluronan. While the literature
      suggests that exogenously added hyaluronan and endogenously produced hyaluronan
      will have varying impacts on extracellular matrix organization and function, no
      studies have directly shown this phenomenon. In this investigation, we
      demonstrate that the addition of exogenous high molecular weight (approximately 1
      MDa) hyaluronan and hyaluronan oligosaccharides have a distinct impact on both
      contraction and strength of smooth muscle cell-seeded collagen gels when compared
      to the effects of hyaluronan that is endogenously produced by the hyaluronan
      synthases. More specifically, the addition of exogenous high molecular weight
      hyaluronan resulted in more compact collagen gels with a higher ultimate tensile
      strength, whereas the endogenous overproduction of hyaluronan resulted in the
      opposite effect. We suggest that the addition of exogenous HA to collagen gels
      represents a model for the therapeutic administration of HA, whereas the addition
      of excess HA to a tissue via the endogenous overexpression of has represents a
      model for the pathological accumulation of HA.

PMID- 19109083
TI  - Impact of perinatal corticosteroids on neuromotor development and outcome: review
      of the literature and new meta-analysis.
AB  - Perinatal corticosteroids are like a double-edged sword. On the one hand, they
      reduce risk for major morbidity and even mortality; on the other hand, they
      modify growth and development of body systems, with short- and long-term
      consequences. The relationship between corticosteroids and neurodevelopmental
      outcome has been extensively studied in randomized controlled trials, cohort and
      case-control studies and meta-analyses. In this article we attempt accurately to
      reflect current clinical equipoise on this issue by reviewing the most recent
      literature and adding a new meta-analysis on the relationship between postnatal
      dexamethasone and cerebral palsy and neurodevelopmental impairment.

PMID- 19109084
TI  - Congenital and opportunistic infections: Ureaplasma species and Mycoplasma
      hominis.
AB  - There is strong evidence from clinical and experimental animal studies that
      ureaplasmas can invade the amnionic sac and induce an inflammatory response
      resulting in chorioamnionitis, preterm labor and neonatal lung injury. The
      ability of Ureaplasma spp. and Mycoplasma hominis to cause pneumonia, bacteremia,
      and meningitis in newborns can no longer be questioned. The association of
      Ureaplasma spp. with bronchopulmonary dysplasia has been supported by the
      majority of observational studies, but proof of causality is still lacking. The
      availability of molecular diagnostic technologies has enabled the designation of
      the two Ureaplasma biovars as individual species, but additional work must be
      done to establish whether there is differential pathogenicity between the
      Ureaplasma spp. or among their respective serovars. Future investigations to
      prevent prematurity should be directed toward identification and localization of
      specific micro-organisms combined with targeted antibiotic trials to determine
      whether such interventions can improve long-term infant outcomes.

PMID- 19109085
TI  - Angiogenesis and osteogenesis of non-vascularised autogenous bone graft with
      arterial pedicle implantation.
AB  - This study aims to investigate the effect of arterial pedicle implantation on
      angiogenesis and osteogenesis of autogenous bone graft. In this study, 36 New
      Zealand white rabbits were evaluated, in which free radial bone grafts without
      periosteum were harvested and implanted into the masseter muscles. In group 1, on
      the one side, the external maxillary artery pedicle was passed through the bone
      marrow cavity. In group 2, on the other hand, as control, no arterial pedicle was
      implanted. Microvessel density was assessed by India ink perfusion and integrated
      optical density of tetracycline fluorescence labelling was used to evaluate
      angiogenesis and new bone formation at 3 days and 1, 2, 3, 4 and 6 weeks
      postoperatively. The bone grafts were found to be re-vascularised at 3 days
      postoperatively in group 1, and at 2 weeks in group 2. At 2, 3 and 4 weeks
      postoperatively, the microvessel densities of group 1 were significantly higher
      than those of group 2. At 4 weeks postoperatively, angiogenesis of group 1
      reached a peak. The tetracycline fluorescence labelling integrated optical
      densities of group 1 were significantly higher than those of group 2 from 2 to 6
      weeks postoperatively. Implantation of arterial pedicle into non-vascularised
      autogenous bone graft enhances angiogenesis, and increased angiogenesis enhances
      osteogenesis.

PMID- 19109086
TI  - Polymorphous low-grade adenocarcinoma: a review regarding an unusual presentation
      as infected odontogenic cyst.
AB  - The World Health Organisation (WHO) classified polymorphous low-grade
      adenocarcinoma (PLGA) in 1990 as a low-grade malignancy; ICD-O 8525/3 being the
      assigned international code. It has been frequently described as occurring in
      hard- or soft-palate accessory salivary glands: some cases being described in the
      tongue and in major salivary glands. We present an extensive literature review
      about PLGA and the most common diagnostic pitfalls. We also report the first case
      where it was seen surrounding an impacted maxillary tooth and discuss it in
      regard to our review.

PMID- 19109087
TI  - Slow midwifery.
AB  - Some patterns of timekeeping and counting are fraught in midwifery. In this paper
      we suggest our societal love affair with all things fast can cause us, as
      midwives, to limit women's possibilities (and our own). We suggest that
      timekeeping and counting potentially disrupt the midwife-woman relationship and,
      further, timekeeping and counting contribute to us valuing particular qualities
      in women and in the health system, including the idea that fast is better than
      slow. Pondering how this could be different, we consider a beginning global trend
      about time and speed--the Slow movement--and suggest a new movement, 'Slow
      Midwifery', in which midwives bear the responsibility of trying to be more
      connected to the women with whom we work by being less connected to our watches.

PMID- 19109088
TI  - Learn ++.NC: combining ensemble of classifiers with dynamically weighted consult
      and-vote for efficient incremental learning of new classes.
AB  - We have previously introduced an incremental learning algorithm Learn(++), which
      learns novel information from consecutive data sets by generating an ensemble of
      classifiers with each data set, and combining them by weighted majority voting.
      However, Learn(++) suffers from an inherent "outvoting" problem when asked to
      learn a new class omega(new) introduced by a subsequent data set, as earlier
      classifiers not trained on this class are guaranteed to misclassify omega(new)
      instances. The collective votes of earlier classifiers, for an inevitably
      incorrect decision, then outweigh the votes of the new classifiers' correct
      decision on omega(new) instances--until there are enough new classifiers to
      counteract the unfair outvoting. This forces Learn(++) to generate an
      unnecessarily large number of classifiers. This paper describes Learn(++).NC,
      specifically designed for efficient incremental learning of multiple new classes
      using significantly fewer classifiers. To do so, Learn (++).NC introduces
      dynamically weighted consult and vote (DW-CAV), a novel voting mechanism for
      combining classifiers: individual classifiers consult with each other to
      determine which ones are most qualified to classify a given instance, and decide
      how much weight, if any, each classifier's decision should carry. Experiments on
      real-world problems indicate that the new algorithm performs remarkably well with
      substantially fewer classifiers, not only as compared to its predecessor
      Learn(++), but also as compared to several other algorithms recently proposed for
      similar problems.

PMID- 19109089
TI  - Fourier-neural-network-based learning control for a class of nonlinear systems
      with flexible components.
AB  - This paper considers an output feedback learning control for a class of uncertain
      nonlinear systems with flexible components. The distinct time delay caused by
      system flexibility leads to the phase lag phenomenon and low system bandwidth.
      Therefore, the tracking problem of such systems is very difficult and
      challenging. To improve the tracking performance of such systems, an iterative
      learning control scheme using the Fourier neural network (FNN) is presented in
      this paper. This scheme uses only local output information for feedback. FNN
      employs orthogonal complex Fourier exponentials as its activation functions and
      the physical meaning of its hidden-layer neurons is clear. The FNN-based learning
      controller introduced here relies on the frequency-domain method, which converts
      the tracking problem in the time domain into a number of regulation problems in
      the frequency domain. A novel phase compensation method is introduced to deal
      with the phase lag phenomenon, so that the bandwidth of the closed-loop system is
      increased. Experiments on a belt-driven positioning table are conducted to show
      the effectiveness of the proposed controller.

PMID- 19109090
TI  - On objective function, regularizer, and prediction error of a learning algorithm
      for dealing with multiplicative weight noise.
AB  - In this paper, an objective function for training a functional link network to
      tolerate multiplicative weight noise is presented. Basically, the objective
      function is similar in form to other regularizer-based functions that consist of
      a mean square training error term and a regularizer term. Our study shows that
      under some mild conditions the derived regularizer is essentially the same as a
      weight decay regularizer. This explains why applying weight decay can also
      improve the fault-tolerant ability of a radial basis function (RBF) with
      multiplicative weight noise. In accordance with the objective function, a simple
      learning algorithm for a functional link network with multiplicative weight noise
      is derived. Finally, the mean prediction error of the trained network is
      analyzed. Simulated experiments on two artificial data sets and a real-world
      application are performed to verify theoretical result.

PMID- 19109091
TI  - Learning assignment order of instances for the constrained K-means clustering
      algorithm.
AB  - The sensitivity of the constrained K-means clustering algorithm (Cop-Kmeans) to
      the assignment order of instances is studied, and a novel assignment order
      learning method for Cop-Kmeans, termed as clustering Uncertainty-based Assignment
      order Learning Algorithm (UALA), is proposed in this paper. The main idea of UALA
      is to rank all instances in the data set according to their clustering
      uncertainties calculated by using the ensembles of multiple clustering
      algorithms. Experimental results on several real data sets with artificial
      instance-level constraints demonstrate that UALA can identify a good assignment
      order of instances for Cop-Kmeans. In addition, the effects of ensemble sizes on
      the performance of UALA are analyzed, and the generalization property of Cop
      Kmeans is also studied.

PMID- 19109092
TI  - Toward the formal verification of a unification system.
AB  - Unification grammars are widely used for encoding human knowledge. For
      unification systems, one major difficulty is the debugging of rules. In this
      paper, the authors suggest a novel method based on model checking to
      theoretically verify a complex grammar system for a unification-based parser. We
      propose the modeling method of the grammar and, more importantly, the abstraction
      method to compress the state space. We apply partial Kripke structures to model
      the rules. We prove that the state space can be reduced by several orders of
      magnitude while still keeping the behaviors of a noncompressed one. Practical
      verification issues are discussed, including the restrictions on specifications,
      the properties to check, etc. The proposed method will contribute to the
      effective debugging and application of unification grammars.

PMID- 19109093
TI  - Type 2 segmental cutaneous leiomyomatosis: an example of mosaicism.

PMID- 19109094
TI  - Immunocytochemistry of matrix proteins in calcified tissues: functional
      biochemistry on section.
AB  - The organic matrix of calcified tissues comprises collagenous and/or
      noncollagenous matrix proteins (NCPs). Identification and precise mapping of
      these matrix components is essential for determining their function, formulating
      coherent hypotheses on their mechanism(s) of action, and developing novel
      therapeutic approaches based on biologics. Fibrillar collagen can be readily
      identified by its conspicuous structure, however, NCPs, in general, do not
      individually exhibit characteristic structural features that permit to identify
      them and morphologically determine their localization. To address this
      limitation, we have used immunocytochemistry, a form of "biochemistry on
      section", to correlate composition with structure. For cytochemical
      characterizations, including immunolabeling, our laboratory has opted for
      colloidal gold labelings and pioneered their application to calcified tissues
      because they yield high spatial resolution and are quantitative. Over the years,
      this approach has been applied to identify and map various NCPs in bone and teeth
      and, in this review of our work, we will emphasize some selected studies that
      highlight it application to also achieve functional information.

PMID- 19109095
TI  - Immunohistochemical localization of dentin matrix protein 1 in human dentin.
AB  - Dentin matrix protein 1 (DMP1) is a non-collagenous matrix protein with a
      recognized role in the formation of mineralized tissues such as dentin. The aim
      of this study was to analyze the distribution of DMP1 in human dentin by means of
      immunofluorescence and high-resolution immunogold labeling. Fully developed,
      sound human dentin specimens were submitted to fluorescence labeling and post
      embedding immunolabeling techniques with a rabbit polyclonal antihuman DMP1
      antibody followed by corresponding fluorochrome-conjugated or gold-conjugated
      secondary antibodies. Both immunofluorescence and immunogold labeling showed an
      intense labeling associated with the peritubular dentin. In addition, at the
      ultrastructural level, there was also a moderate and diffuse immunoreaction over
      intertubular dentin, and a weak labeling within predentin which increased in
      density towards the mineralization front. This study suggests that in adult human
      teeth, like in rodents, DMP1 is prevalently concentrated at the level of
      peritubular dentin and this feature is preserved also in fully developed-teeth.
      These data are consistent with what has been observed in rodents and suggest that
      DMP1 plays a role in maintenance of the dentin tubular space.

PMID- 19109096
TI  - Upon oxidative stress, the antiapoptotic Hsp60/procaspase-3 complex persists in
      mucoepidermoid carcinoma cells.
AB  - Hsp60, a mitochondrial chaperonin highly conserved during evolution, has been
      found elevated in the cytosol of cancer cells, both in vivo and in vitro, but its
      role in determining apoptosis during oxidative stress (OS) has not yet been fully
      elucidated. The aim of the present work was to study the effects of OS on Hsp60
      levels and its interactions with procaspase- 3 (p-C3) and p53 in tumor cells. NCI
      H292 (mucoepidermoid carcinoma) cells were exposed to various concentrations of
      hydrogen peroxide (H2O2) for 24 hours. Cell viability was determined by Trypan
      blue and MTT assays. DNA damage was assessed by the Comet assay, and apoptosis
      was measured by the AnnexinV cytofluorimetric test. Exposure to increasing
      concentrations of H2O2 resulted in a reduction of cell viability, DNA damage, and
      early apoptotic phenomena. Hsp60, p-C3, p53, and p21 were assessed by Western
      blotting and immunocytochemistry before and after OS. Hsp60 and p-C3 were present
      before and after OS induction. Immunoprecipitation experiments showed an Hsp60/p
      C3 complex before OS that persisted after it, while an Hsp60/p53 complex was not
      detected in either condition. The presence of wild type (wt) p53 was confirmed by
      RT-PCR, and p21 detection suggested p53 activation after OS. We postulate that,
      although OS may induce early apoptosis in NCI-H292 cells, Hsp60 exerts an anti
      apoptotic effect in these cells and, by extension, it may do so in other cancer
      cells.

PMID- 19109097
TI  - Identification of orexin A- and orexin type 2 receptor-positive cells in the
      gastrointestinal tract of neonatal dogs.
AB  - The presence and distribution of cells positive to orexin A (OXA) and to orexin
      type 2 receptor (OX2R) were investigated in the gastrointestinal tract of
      neonatal dogs by means of immunohistochemical techniques. The orexin A-positive
      cells were identified with some of the endocrine cells in the stomach and in the
      duodenum; they were both of the open and closed type and were lacking in the
      large intestine. In the stomach, a large subset of orexin A-positive cells also
      showed gastrin-like immunoreactivity while, in the duodenum, many of them seemed
      to store serotonin. The orexin type 2 receptor-positive cells were evidenced all
      along the gastrointestinal tract examined, also in the large intestine, and they
      showed the same morphological characteristics as those positive to orexin A.
      Moreover, the immunohistochemical techniques revealed intense positivity for both
      orexin A and orexin type 2 receptor in the neurons and fibers of the enteric
      nervous system. A large subset of orexin A-positive neurons seemed to store
      substance P.

PMID- 19109098
TI  - Distribution and density of mast cells in camel small intestine and influence of
      fixation techniques.
AB  - This study was carried out to gather species-specific data on mast-cell density
      and distribution in camel small intestine under different fixation conditions and
      to elucidate the presence and cross-reactivity of tryptase in the camel small
      intestine using human specific anti-tryptase antibody. Tissue specimens from the
      jejunum, duodenum, and ileum were obtained from 9 healthy, 9-12 months old, male
      camels. Specimens were fixed either with carnoy's fluid or formalinbuffered
      solution and stained with either methylene blue or immunohistochemically to
      identify mast cells. The present study demonstrated for the first time, the
      presence and cross-reactivity of tryptase in the camel small intestine using a
      specific mouse anti-human tryptase antibody. Mast cells were detected in all
      histological layers of the camel small intestine (mucosal, submucosal, muscularis
      externa and serosa). Among all locations examined in the duodenum, ileum and
      jejunum, no significant difference was observed in mast-cell counts among the
      lamina propria, muscularis mucosae, muscularis externa and the serosa. The only
      significant difference observed was the mast-cell count in submucosa region where
      the highest and lowest mast count was observed in the jejenual and ileal
      submucosa, respectively. Significant differences regarding the distribution of
      mast cell as well as the influence of the fixation method could be observed. This
      underlines the fact that data regarding mast cell heterogeneity from other
      species, obtained by different fixation methods, are not comparable. This fact
      has to be taken into account when evaluating mast cell subtypes under
      pathological conditions.

PMID- 19109099
TI  - Temporal and spatial expression of TGF-beta2 in tooth crown development in mouse
      first lower molar.
AB  - Transforming Growth Factor beta2 (TGF-beta2) is involved in the regulation of
      many important cellular processes during tooth development. In this study we
      systematically characterized the expression pattern of TGF-beta2 in vivo and
      further analyzed its possible roles during different developmental stages of
      mouse first lower molar using immunofluorescence histochemical method with
      confocal microscopy. TGF-beta2 signaling was detected in different developing
      stages in both dental epithelium and surrounding dental mesenchyme. For the first
      time, we found that the basement membrane and epithelial cells in the basal layer
      showed no immunostaining from embryonic day 11 to 13; the primary enamel knot and
      secondary enamel knot exhibited pronounced immunostaining with different
      expression patterns at embryonic day 14 and 16. In addition, the mature
      ameloblast lost immunoreactivity, but the secretory ameloblast still exhibited
      positive immunoreaction at day 2 of postnatal development. Collectively, the
      temporospatial distribution patterns of TGF- beta2, especially in the basement
      membrane, epithelial cells in the basal layer, enamel knot, mature odontoblast
      and ameloblast, suggested a close association between TGF-beta2 signaling and
      tooth crown development, and indicated that TGF-beta2 might participate in tooth
      initiation, epithelial morphogenesis, formation of dentine matrix, and ameloblast
      differentiation.

PMID- 19109100
TI  - The role of immunohistochemistry in the diagnosis of hyalinizing clear cell
      carcinoma of the minor salivary gland: a case report.
AB  - A case of hyalinizing clear cell carcinoma (HCCC) of the minor salivary glands of
      the oral cavity is reported. A 52- year-old woman presented with a growing mass
      at the base of the tongue. The patient underwent complete resection of the
      tumour. The histological picture was characterized by trabeculae or solid nests
      of proliferating cells with a clear cytoplasm, surrounded by a hyalinizing
      stroma. Tumour cells were immunoreactive for Cytokeratins 5, 6, 7, 8, 14, 17 and
      18. No reactivity was observed for cytokeratin 20, vimentin, S- 100 protein,
      smooth-muscle actin, muscle-specific actin, and calponin. These findings
      confirmed the diagnosis of HCCC of minor salivary glands of the oral cavity. The
      clinical presentation, the immunohistochemical pattern and the role of
      cytokeratins in the differential diagnosis of HCCC are discussed with a review of
      the literature.

PMID- 19109101
TI  - Acid invertase localization in leaves of the fern Pteris deflexa link.
AB  - The localization of invertase, a key enzyme in plant carbohydrate metabolism, has
      been established in several higher plants, but there are no reports of it in
      ferns. The aim of the present work was to establish the localization of the
      previously reported acid invertase activity of Pteris deflexa in fronds tissues
      and to compare the findings with invertase localization in higher plants. Acid
      invertase, localized by immuno-histochemical and histochemical techniques on
      fresh tissues, was evident in vascular tissue, mainly in phloem. It was also
      detected in parenchymatic, sclerenchymatic and epidermic cells of petiole, rachis
      and rachis branches as well as in veins of leaf blades. Our results demonstrate
      that P. deflexa acid invertase localization is the same to that of higher plants.
      Hence, potential roles of the fern enzyme in relation to the storage and
      utilization of sucrose and to control carbon flux could be the same of those
      proposed to higher plants.

PMID- 19109102
TI  - Can a genetically-modified organism-containing diet influence embryo development?
      A preliminary study on pre-implantation mouse embryos.
AB  - In eukaryotic cells, pre-mRNAs undergo several transformation steps to generate
      mature mRNAs. Recent studies have demonstrated that a diet containing a
      genetically modified (GM) soybean can induce modifications of nuclear
      constituents involved in RNA processing in some tissues of young, adult and old
      mice. On this basis, we have investigated the ultrastructural and
      immunocytochemical features of pre-implantation embryos from mice fed either GM
      or non- GM soybean in order to verify whether the parental diet can affect the
      morpho-functional development of the embryonic ribonucleoprotein structural
      constituents involved in pre-mRNA pathways. Morphological observations revealed
      that the general aspect of embryo nuclear components is similar in the two
      experimental groups. However, immunocytochemical and in situ hybridization
      results suggest a temporary decrease of pre-mRNA transcription and splicing in 2
      cell embryos and a resumption in 4-8-cell embryos from mice fed GM soybean;
      moreover, pre-mRNA maturation seems to be less efficient in both 2-cell and 4-8
      cell embryos from GM-fed mice than in controls. Although our results are still
      preliminary and limited to the pre-implantation phases, the results of this study
      encourage deepening on the effects of food components and/or contaminants on
      embryo development.

PMID- 19109104
TI  - A piece of my mind. Trying not to miss the point.

PMID- 19109103
TI  - The cover. Dance.

PMID- 19109105
TI  - Fogarty at 40: NIH center updates its strategies for supporting global health.

PMID- 19109106
TI  - US health care system earns poor marks.

PMID- 19109107
TI  - Medical personnel's role in US detainees' interrogations questioned.

PMID- 19109108
TI  - FDA: Epilepsy drugs may carry skin risks for Asians.

PMID- 19109109
TI  - Lowering homocysteine with B vitamins in patients with coronary artery disease.

PMID- 19109110
TI  - Lowering homocysteine with B vitamins in patients with coronary artery disease.

PMID- 19109111
TI  - Lowering homocysteine with B vitamins in patients with coronary artery disease.

PMID- 19109112
TI  - Erythropoiesis-stimulating agents in the treatment of cancer-associated anemia.

PMID- 19109113
TI  - Erythropoiesis-stimulating agents in the treatment of cancer-associated anemia.

PMID- 19109114
TI  - Short sleep duration and incident coronary artery calcification.
AB  - CONTEXT: Coronary artery calcification is a subclinical predictor of coronary
      heart disease. Recent studies have found that sleep duration is correlated with
      established risk factors for calcification including glucose regulation, blood
      pressure, sex, age, education, and body mass index. OBJECTIVE: To determine
      whether objective and subjective measures of sleep duration and quality are
      associated with incidence of calcification over 5 years and whether calcification
      risk factors mediate the association. DESIGN, SETTING, AND PARTICIPANTS:
      Observational cohort of home monitoring in a healthy middle-aged population of
      495 participants from the Coronary Artery Risk Development in Young Adults
      (CARDIA) cohort Chicago site (black and white men and women aged 35-47 years at
      year 15 of the study in 2000-2001 with follow-up data at year 20 in 2005-2006).
      Potential confounders (age, sex, race, education, apnea risk, smoking status) and
      mediators (lipids, blood pressure, body mass index, diabetes, inflammatory
      markers, alcohol consumption, depression, hostility, self-reported medical
      conditions) were measured at both baseline and follow-up. Sleep metrics (wrist
      actigraphy measured duration and fragmentation, daytime sleepiness, overall
      quality, self-reported duration) were examined for association with incident
      calcification. Participants had no detectable calcification at baseline. MAIN
      OUTCOME MEASURE: Coronary artery calcification was measured by computed
      tomography in 2000-2001 and 2005-2006 and incidence of new calcification over
      that time was the primary outcome. RESULTS: Five-year calcification incidence was
      12.3% (n = 61). Longer measured sleep duration was significantly associated with
      reduced calcification incidence (adjusted odds ratio, 0.67 per hour [95%
      confidence interval, 0.49-0.91 per hour]; P = .01). No potential mediators
      appreciably altered the magnitude or significance of sleep (adjusted odds ratio
      estimates ranged from 0.64 to 0.68 per sleep hour; maximum P = .02). Alternative
      sleep metrics were not significantly associated with calcification. CONCLUSION:
      Longer measured sleep is associated with lower calcification incidence
      independent of examined potential mediators and confounders.

PMID- 19109115
TI  - Use of prescription and over-the-counter medications and dietary supplements
      among older adults in the United States.
AB  - CONTEXT: Despite concerns about drug safety, current information on older adults'
      use of prescription and over-the-counter medications and dietary supplements is
      limited. OBJECTIVE: To estimate the prevalence and patterns of medication use
      among older adults (including concurrent use), and potential major drug-drug
      interactions. DESIGN, SETTING, AND PARTICIPANTS: Three thousand five community
      residing individuals, aged 57 through 85 years, were drawn from a cross
      sectional, nationally representative probability sample of the United States. In
      home interviews, including medication logs, were administered between June 2005
      and March 2006. Medication use was defined as prescription, over-the-counter, and
      dietary supplements used "on a regular schedule, like every day or every week."
      Concurrent use was defined as the regular use of at least 2 medications. MAIN
      OUTCOME MEASURE: Population estimates of the prevalence of medication use,
      concurrent use, and potential major drug-drug interactions, stratified by age
      group and gender. RESULTS: The unweighted survey response rate was 74.8%
      (weighted response rate, 75.5%). Eighty-one percent (95% confidence interval
      [CI], 79.4%-83.5%) used at least 1 prescription medication, 42% (95% CI, 39.7%
      44.8%) used at least 1 over-the-counter medication, and 49% (95% CI, 46.2%-52.7%)
      used a dietary supplement. Twenty-nine percent (95% CI, 26.6%-30.6%) used at
      least 5 prescription medications concurrently; this was highest among men (37.1%;
      95% CI, 31.7%-42.4%) and women (36.0%; 95% CI, 30.2%-41.9%) aged 75 to 85 years.
      Among prescription medication users, concurrent use of over-the-counter
      medications was 46% (95% CI, 43.4%-49.1%) and concurrent use of dietary
      supplements was 52% (95% CI, 48.8%-55.5%). Overall, 4% of individuals were
      potentially at risk of having a major drug-drug interaction; half of these
      involved the use of nonprescription medications. These regimens were most
      prevalent among men in the oldest age group (10%; 95% CI, 6.4%-13.7%) and nearly
      half involved anticoagulants. No contraindicated concurrent drug use was
      identified. CONCLUSIONS: In this sample of community-dwelling older adults,
      prescription and nonprescription medications were commonly used together, with
      nearly 1 in 25 individuals potentially at risk for a major drug-drug interaction.

PMID- 19109117
TI  - Birth weight and risk of type 2 diabetes: a systematic review.
AB  - CONTEXT: Low birth weight is implicated as a risk factor for type 2 diabetes.
      However, the strength, consistency, independence, and shape of the association
      have not been systematically examined. OBJECTIVE: To conduct a quantitative
      systematic review examining published evidence on the association of birth weight
      and type 2 diabetes in adults. DATA SOURCES AND STUDY SELECTION: Relevant studies
      published by June 2008 were identified through literature searches using EMBASE
      (from 1980), MEDLINE (from 1950), and Web of Science (from 1980), with a
      combination of text words and Medical Subject Headings. Studies with either
      quantitative or qualitative estimates of the association between birth weight and
      type 2 diabetes were included. DATA EXTRACTION: Estimates of association (odds
      ratio [OR] per kilogram of increase in birth weight) were obtained from authors
      or from published reports in models that allowed the effects of adjustment (for
      body mass index and socioeconomic status) and the effects of exclusion (for
      macrosomia and maternal diabetes) to be examined. Estimates were pooled using
      random-effects models, allowing for the possibility that true associations
      differed between populations. DATA SYNTHESIS: Of 327 reports identified, 31 were
      found to be relevant. Data were obtained from 30 of these reports (31
      populations; 6090 diabetes cases; 152 084 individuals). Inverse birth weight-type
      2 diabetes associations were observed in 23 populations (9 of which were
      statistically significant) and positive associations were found in 8 (2 of which
      were statistically significant). Appreciable heterogeneity between populations
      (I(2) = 66%; 95% confidence interval [CI], 51%-77%) was largely explained by
      positive associations in 2 native North American populations with high
      prevalences of maternal diabetes and in 1 other population of young adults. In
      the remaining 28 populations, the pooled OR of type 2 diabetes, adjusted for age
      and sex, was 0.75 (95% CI, 0.70-0.81) per kilogram. The shape of the birth weight
      type 2 diabetes association was strongly graded, particularly at birth weights of
      3 kg or less. Adjustment for current body mass index slightly strengthened the
      association (OR, 0.76 [95% CI, 0.70-0.82] before adjustment and 0.70 [95% CI,
      0.65-0.76] after adjustment). Adjustment for socioeconomic status did not
      materially affect the association (OR, 0.77 [95% CI, 0.70-0.84] before adjustment
      and 0.78 [95% CI, 0.72-0.84] after adjustment). There was no strong evidence of
      publication or small study bias. CONCLUSION: In most populations studied, birth
      weight was inversely related to type 2 diabetes risk.

PMID- 19109116
TI  - Insurance parity and the use of outpatient mental health care following a
      psychiatric hospitalization.
AB  - CONTEXT: Mental health services are typically subject to higher cost sharing than
      other health services. In 2008, the US Congress enacted legislation requiring
      parity in insurance coverage for mental health services in group health plans and
      Medicare Part B. OBJECTIVE: To determine the relationship between mental health
      insurance parity and the use of timely follow-up care after a psychiatric
      hospitalization. DESIGN, SETTING, AND POPULATION: We reviewed cost-sharing
      requirements for outpatient mental health and general medical services for 302
      Medicare health plans from 2001 to 2006. Among 43 892 enrollees in 173 health
      plans who were hospitalized for a mental illness, we determined the relation
      between parity in cost sharing and receipt of timely outpatient mental health
      care after discharge using cross-sectional analyses of all Medicare plans and
      longitudinal analyses of 10 plans that discontinued parity compared with 10
      matched control plans that maintained parity. MAIN OUTCOME MEASURES: Outpatient
      mental health visits within 7 and 30 days following a discharge for a psychiatric
      hospitalization. RESULTS: More than three-quarters of Medicare plans,
      representing 79% of Medicare enrollees, required greater cost sharing for mental
      health care compared with primary or specialty care. The adjusted rate of follow
      up within 30 days after a psychiatric hospitalization was 10.9 percentage points
      greater (95% confidence interval [CI], 4.6-17.3; P < .001) in plans with
      equivalent cost sharing for mental health and primary care compared with plans
      with mental health cost sharing greater than primary and specialty care cost
      sharing. The association of parity with follow-up care was increased for
      enrollees from areas of low income and less education. Rates of follow-up visits
      within 30 days decreased by 7.7 percentage points (95% CI, -12.9 to -2.4; P =
      .004) in plans that discontinued parity and increased by 7.5 percentage points
      (95% CI, 2.0-12.9; P = .008) among control plans that maintained parity (adjusted
      difference in difference, 14.2 percentage points; 95% CI, 4.5-23.9; P = .007).
      CONCLUSION: Medicare enrollees in health plans with insurance parity for mental
      health and primary care have markedly higher use of clinically appropriate mental
      health services following a psychiatric hospitalization.

PMID- 19109118
TI  - Agitation and delirium at the end of life: "We couldn't manage him".
AB  - Delirium is the most common neuropsychiatric complication experienced by patients
      with advanced illness, occurring in up to 85% of patients in the last weeks of
      life. Using the case of Mr L, a 59-year-old man with metastatic lung cancer who
      developed an agitated delirium in the last week of life, we review the evaluation
      and management of delirium near the end of life. Although some studies have
      identified agitation as a central feature of delirium in 13% to 46% of patients,
      other studies have found up to 80% of patients near the end of life develop a
      hypoactive, nonagitated delirium. Both the agitated (hyperactive) and nonagitated
      (hypoactive) forms of delirium are harbingers of impending death and are
      associated with increased morbidity in patients who are terminally ill, causing
      distress for patients, family members, and staff. Delirium is a sign of
      significant physiological disturbance, usually involving multiple causes,
      including infection, organ failure, and medication adverse effects. Often these
      causes of delirium are not reversible in the dying patient, and this influences
      the outcomes of its management. Delirium can also significantly interfere with
      the recognition and control of other physical and psychological symptoms, such as
      pain. Unfortunately, delirium is often misdiagnosed or unrecognized and thus
      inappropriately treated or untreated in terminally ill patients. To manage
      delirium in terminally ill patients, clinicians must be able to diagnose it
      accurately, undertake appropriate assessment of underlying causes, and understand
      the benefits and risks of the available pharmacological and nonpharmacological
      interventions.

PMID- 19109119
TI  - Carbapenem-resistant Enterobacteriaceae: a potential threat.

PMID- 19109120
TI  - Physician autonomy and informed decision making: finding the balance for patient
      safety and quality.

PMID- 19109121
TI  - The physician as public health professional in the 21st century.

PMID- 19109122
TI  - The power of hope.

PMID- 19109123
TI  - Update on JAMA-EXPRESS: rapid review and publication.

PMID- 19109124
TI  - JAMA patient page. Delirium.

PMID- 19109125
TI  - Comment on "Cutting edge: inhibition of NF-kappa B-mediated TSLP expression by
      retinoid X receptor".

PMID- 19109126
TI  - The surprising discovery that TGF beta specifically induces the IgA class switch.

PMID- 19109127
TI  - Transforming growth factor beta specifically enhances IgA production by
      lipopolysaccharide-stimulated murine B lymphocytes. J. Exp. Med. 1989. 170: 1039
      1044.

PMID- 19109128
TI  - Transforming growth factor beta induces IgA production and acts additively with
      interleukin 5 for IgA production. J. Exp. Med. 1989. 170: 1415-1420.

PMID- 19109129
TI  - Insights into the role of STAT3 in human lymphocyte differentiation as revealed
      by the hyper-IgE syndrome.
AB  - "Experiments of nature" due to single gene mutations resulting in human
      immunodeficiency states have revealed critical roles for several genes in
      regulating lymphocyte development and the generation of protective immunity.
      Recently, heterozygous mutations in STAT3 were found to cause autosomal dominant
      hyper-IgE syndrome, a condition affecting not only the immune system but also
      other mesenchymal and ectodermal tissues, including bones, cranium, teeth, and
      skin. STAT proteins operate to integrate signals from surface receptors,
      including cytokine receptors, that regulate growth and differentiation of
      multiple cell lineages. In this article, we will review how the study of STAT3
      deficiency in humans and mice has highlighted nonredundant roles of STAT3, and of
      specific cytokines, in diverse cellular processes such as antimicrobial immunity
      and protection at epithelial barriers, the generation of functional humoral
      immune responses, bone formation, and keratinocyte biology.

PMID- 19109130
TI  - Cutting edge: antigen presentation to CD8 T cells after influenza A virus
      infection.
AB  - Influenza A virus infection induces massive inflammation and lung damage.
      Activation of CD8 T cells by dendritic cells (DCs) is necessary to control
      disease. We undertook studies to track directly Ag presentation to CD8 T cells in
      vivo through the first 72 h after infection with OVA-expressing influenza A
      virus. We found that Ag presentation by DCs occurs strictly in the draining lymph
      nodes and not within the lung itself. Surprisingly, Ag presentation was found to
      be mediated by a CD11b(+) DC population. Finally, the expression of antigenic
      complexes on DCs correlated with the location and timing of CD8 T cell
      activation. These results have implications for approaches to control influenza A
      virus infection.

PMID- 19109131
TI  - Cutting edge: autoimmune disease risk variant of STAT4 confers increased
      sensitivity to IFN-alpha in lupus patients in vivo.
AB  - Increased IFN-alpha signaling is a primary pathogenic factor in systemic lupus
      erythematosus (SLE). STAT4 is a transcription factor that is activated by IFN
      alpha signaling, and genetic variation of STAT4 has been associated with risk of
      SLE and rheumatoid arthritis. We measured serum IFN-alpha activity and
      simultaneous IFN-alpha-induced gene expression in PBMC in a large SLE cohort. The
      risk variant of STAT4 (T allele; rs7574865) was simultaneously associated with
      both lower serum IFN-alpha activity and greater IFN-alpha-induced gene expression
      in PBMC in SLE patients in vivo. Regression analyses confirmed that the risk
      allele of STAT4 was associated with increased sensitivity to IFN-alpha signaling.
      The IFN regulatory factor 5 SLE risk genotype was associated with higher serum
      IFN-alpha activity; however, STAT4 showed dominant influence on the sensitivity
      of PBMC to serum IFN-alpha. These data provide biologic relevance for the risk
      variant of STAT4 in the IFN-alpha pathway in vivo.

PMID- 19109132
TI  - Cutting edge: down-regulation of MHC class I-related chain A on tumor cells by
      IFN-gamma-induced microRNA.
AB  - NKG2D is a receptor used by NK cells to detect virally infected and transformed
      cells. It recognizes ligands that are expressed constitutively on primary tumors
      and tumor cell lines. In this report, we have identified four microRNAs (miRNAs)
      that each was sufficient to reduce the expression of the NKG2D ligand MHC class I
      related chain A (MICA). One of these miRNAs (miR-520b) was induced by IFN-gamma,
      leading to a reduction in MICA surface protein levels. Interestingly, miR-520b
      acted on both the MICA 3'-untranslated region and the promoter region and caused
      a decrease in the levels of MICA transcript. In contrast, an antisense
      oligonucleotide inhibitor of miR-520b increased the expression of a reporter
      construct containing the MICA 3'-untranslated region but not the MICA promoter
      region. These findings demonstrate the novel regulation of an NKG2D ligand by an
      endogenous microRNA that is itself induced by IFN-gamma.

PMID- 19109133
TI  - Cutting edge: developmental stage-specific recruitment of cohesin to CTCF sites
      throughout immunoglobulin loci during B lymphocyte development.
AB  - Contraction of the large Igh and Igkappa loci brings all V genes, spanning >2.5
      Mb in each locus, in proximity to DJ(H) or J(kappa) genes. CCCTC-binding factor
      (CTCF) is a transcription factor that regulates gene expression by long-range
      chromosomal looping. We therefore hypothesized that CTCF may be crucial for the
      contraction of the Ig loci, but no CTCF sites have been described in any V loci.
      Using ChIP-chip, we demonstrated many CTCF sites in the V(H) and V(kappa)
      regions. However, CTCF enrichment in the Igh locus, but not the Igkappa locus,
      was largely unchanged throughout differentiation, suggesting that CTCF binding
      alone cannot be responsible for stage-specific looping. Because cohesin can
      colocalize with CTCF, we performed chromatin immunoprecipitation for the cohesin
      subunit Rad21 and found lineage and stage-specific Rad21 recruitment to CTCF in
      all Ig loci. The differential binding of cohesin to CTCF sites may promote
      multiple loop formation and thus effective V(D)J recombination.

PMID- 19109134
TI  - Cutting edge: the metalloproteinase ADAM17/TNF-alpha-converting enzyme regulates
      proteolytic shedding of the MHC class I-related chain B protein.
AB  - MHC class I-related chain (MIC) A/B are transmembrane proteins expressed in
      pathological conditions that are ligands for the activating receptor NKG2D found
      on cytotoxic lymphocytes. Soluble NKG2D ligands are detected in sera of patients
      suffering from multiple types of cancer where they are associated with reduced
      levels of receptor expression and compromised function of NK and CTLs. In this
      study, we report the identification of a metalloproteinase involved in the
      cleavage process of MIC; inhibition and knockdown of ADAM17/TACE blocks the
      shedding of these proteins. Strikingly, the recruitment of both enzyme and
      substrate to detergent-resistant membrane microdomains is crucial for efficient
      proteolysis. These findings provide a novel insight into the molecular mechanisms
      of MIC shedding.

PMID- 19109135
TI  - Activated human neonatal CD8+ T cells are subject to immunomodulation by direct
      TLR2 or TLR5 stimulation.
AB  - In conditions of optimal priming, the neonate possesses competency to mount
      quantitatively adult-like responses. Vaccine formulations containing sufficiently
      potent adjuvants may overcome the neonate's natural tendency for
      immunosuppression and provoke a similarly robust immune response. TLR expression
      on T cells represents the possibility of directly enhancing T cell immunity. We
      examined the ex vivo responsiveness of highly purified human cord blood-derived
      CD8(+) T cells to direct TLR ligation by a repertoire of TLR agonists. In concert
      with TCR stimulation, only Pam(3)Cys (palmitoyl-3-Cys-Ser-(Lys)(4)) and flagellin
      monomers significantly enhanced proliferation, CD25(+) expression, IL-2, IFN
      gamma, TNF-alpha, and intracellular granzyme B expression. TLR2 and TLR5 mRNA was
      detected in the CD8(+) T cells. Blocking studies confirmed that the increase in
      IFN-gamma production was by the direct triggering of surface TLR2 or TLR5. The
      simultaneous exposure of CD8(+) T cells to both TLR agonists had an additive
      effect on IFN-gamma production. These data suggest that a combination of the two
      TLR ligands would be a potent T cell adjuvant. This may represent a new approach
      to TLR agonist-based adjuvant design for future human neonatal vaccination
      strategies requiring a CD8(+) component.

PMID- 19109136
TI  - Identification and characterization of a transmembrane isoform of CD160 (CD160
      TM), a unique activating receptor selectively expressed upon human NK cell
      activation.
AB  - CD160 has been initially identified as a GPI-anchored MHC-class I activating
      receptor mainly expressed on peripheral blood NK cells. Herein, we report the
      identification of three additional CD160-related mRNAs generated through
      alternative splicings of the CD160 gene, among which one encoded a putative CD160
      transmembrane isoform (CD160-TM). We first establish that CD160-TM surface
      expression is highly restricted to NK cells and is activation-dependent.
      Additionally, we provide evidence that CD160-TM represents a novel activating
      receptor, as assessed by the increased CD107a NK cell surface mobilization
      observed upon its engagement. Finally, we demonstrate that the CD160-TM
      cytoplasmic tail is by itself sufficient to mediate the recruitment of Erk1/2
      signaling pathway, and that the initiation of this activation process is
      dependent on the Src-family kinase p56(lck). The identification of CD160-TM
      therefore provides new possibilities regarding the role of CD160 isoforms in the
      regulation of NK cell functions.

PMID- 19109137
TI  - Airway epithelial cells regulate the functional phenotype of locally
      differentiating dendritic cells: implications for the pathogenesis of infectious
      and allergic airway disease.
AB  - Atopic asthma pathogenesis is driven by the combined effects of airway
      inflammation generated during responses to viral infections and aeroallergens,
      and both these pathways are regulated by dendritic cells (DC) that differentiate
      locally from monocytic precursors. These DCs normally exhibit a sentinel
      phenotype characterized by active Ag sampling but attenuated presentation
      capability, which limits the intensity of local expression of adaptive immunity.
      How this tight control of airway DC functions is normally maintained, and why it
      breaks down in some atopics leading to immunopathological changes in airway
      tissues, is unknown. We postulated that signals from adjacent airway epithelial
      cells (AEC) contribute to regulation of local differentiation of DC. We tested
      this in a coculture model containing both cell types in a GM-CSF-IL-4-enriched
      cytokine milieu characteristic of the atopic asthmatic airway mucosa. We
      demonstrate that contact with AEC during DC differentiation up-regulates
      expression of the function-associated markers MHC class II, CD40, CD80, TLR3, and
      TLR4 on DCs with concomitant up-regulation of Ag uptake/processing. Moreover, the
      AEC-conditioned DCs displayed increased LPS responsiveness evidenced by higher
      production of IL-12, IL-6, IL-10, and TNF-alpha. The Th2 memory-activating
      properties of AEC-conditioned DCs were also selectively attenuated. Data from
      microarray and blocking experiments implicate AEC-derived type 1 IFNs and IL-6 in
      modulation of DC differentiation. Collectively, these findings suggest that
      resting AECs modulate local DC differentiation to optimize antimicrobial defenses
      in the airways and in the process down-modulate capacity for expression of
      potentially damaging Th2 immunity.

PMID- 19109139
TI  - Functional analysis of killer Ig-like receptor-expressing cytomegalovirus
      specific CD8+ T cells.
AB  - Killer Ig-like receptors (KIR) are expressed by human NK cells and T cells.
      Although Ag-specific cytolytic activity and cytokine production of KIR(+) T cells
      can be inhibited by KIR ligation, the effect of KIR on proliferation is unclear.
      KIR(+) T cells have been reported to have a general proliferative defect. To
      investigate whether KIR(+) T cells represent end-stage dysfunctional T cells, we
      characterized KIR(+) CMV-specific T cells in allogeneic stem cell transplantation
      patients and healthy donors. In both patients and healthy donors, a significant
      percentage KIR(+) T cells was detected at various time points. All stem cell
      transplantation patients studied showed KIR expression on CMV-specific T cells,
      while not all donors had KIR-expressing CMV-specific T cells. From two of the
      patients and one donor KIR(+) CMV-specific T clones were isolated and analyzed
      functionally. T cells were detected that expressed KIR that could not encounter
      their corresponding KIR ligands in vivo, illustrating that KIR expression by
      these T cells was not based on functional selection but a random process. Our
      data demonstrate that KIR(+) T cells are fully functional T cells that are only
      restricted in effector functions and proliferation upon KIR ligation. The level
      of KIR-mediated inhibition of the effector functions and proliferation depended
      on the strength of TCR stimulation. We observed no diminished general
      proliferative capacity and therefore we conclude that these T cells do not
      represent end-stage dysfunctional T cells.

PMID- 19109138
TI  - App1: an antiphagocytic protein that binds to complement receptors 3 and 2.
AB  - In previous studies, we showed that the pathogenic fungus Cryptococcus neoformans
      (Cn) produces a specific and unique protein called antiphagocytic protein 1
      (App1), which inhibits phagocytosis of Cn by alveolar macrophages (AMs).
      Phagocytosis of Cn by AMs occurs mainly through a complement- or Ab-mediated
      mechanism. Among AM receptors, complement receptor 3 (CR3) and FcRgamma are the
      most common receptors involved in the phagocytic process. Because App1 inhibits
      phagocytosis of complement- but not Ab-coated erythrocytes, we investigated the
      role of CR3 in App1-macrophage interactions. We found that App1 binds to CR3 and
      if CR3 is absent from the surface of AMs, its antiphagocytic action is lost. When
      we investigated whether App1 would also bind to other complement receptor(s), we
      found that App1 does bind to complement receptor 2 (CR2) in a dose-dependent
      manner. In certain lymphoma cell lines, cellular proliferation is stimulated by
      complement through CR2, providing a potential use of App1 as a proliferation
      inhibitor of these cells. Initially discovered as an antiphagocytic protein
      regulating CR3-mediated innate immunity, App1 may also play a key role in the
      regulation of acquired immunity, because CR2 is mainly localized on B cells.

PMID- 19109140
TI  - CD28 signaling in T regulatory precursors requires p56lck and rafts integrity to
      stabilize the Foxp3 message.
AB  - Naturally occurring CD4(+)25(high)Foxp3(+) T regulatory (T-reg) cells are
      critical for maintaining tolerance to self and non-self Ags. The Foxp3 master
      regulatory gene and CD28 costimulation are both required for thymic development
      and suppressogenic function of CD4(+)25(high)Foxp3(+) T-regs. Herein, we show
      that the sole CD28 stimulation of T-reg thymic precursors augments Foxp3
      expression through the increase in Foxp3 mRNA life span by a mechanism involving
      p56(lck) and its binding motif on CD28 cytosolic tail, as well as the lipid
      rafts. We found that 1) the glycosphingolipids and cholesterol components of
      lipid rafts were highly expressed and unusually partitioned in T-reg thymic
      precursors as compared with the conventional T cell precursors, 2) the CD28
      receptor density on cell membrane is proportional with the content of cholesterol
      in lipid rafts and with the level of Foxp3 mRNA expression in T-reg precursors,
      and 3) the CD28-mediated increase of Foxp3 mRNA life span was paralleled by an
      increased proliferative and suppressogenic capacity of terminally differentiated
      CD4(+)25(high)Foxp3(+) T-reg precursors. Thus, the functional integrity of CD28
      receptor p56(lck) and plasma membrane lipid rafts are all prerequisites for up
      regulation and long-term expression of Foxp3 mRNA transcripts in
      CD4(+)25(high)Foxp3(+) T-reg precursors.

PMID- 19109141
TI  - CD69+ CD4+ CD25- T cells, a new subset of regulatory T cells, suppress T cell
      proliferation through membrane-bound TGF-beta 1.
AB  - The underlying mechanisms of tumor-induced immune suppression need to be fully
      understood. Regulatory T (Treg) cells have been shown to play an important role
      in tumor immune escape. Until now, many subsets of Treg cells have been described
      that can suppress T cell response via different mechanisms. CD69 is generally
      regarded as one of the activating markers; however, recent studies show that CD69
      may exert regulatory function in the immune response. In this study, we have
      identified tumor-induced CD69(+)CD4(+)CD25(-) T cells as a new subset of CD4(+)
      Treg cells. CD69(+)CD4(+)CD25(-) T cells increase dramatically along tumor
      progression, with up to 40% of CD4(+) T cells in the advanced tumor-bearing mice.
      Distinct from the previously described CD4(+) Treg cell subsets,
      CD69(+)CD4(+)CD25(-) T cells express high CD122, but they do not express Foxp3
      and secrete IL-10, TGF-beta1, IL-2, and IFN-gamma. CD69(+)CD4(+)CD25(-) T cells
      are hyporesponsive and can suppress CD4(+) T cell proliferation in a cell-cell
      contact manner. Interestingly, the fixed CD69(+)CD4(+)CD25(-) T cells still have
      suppressive activity, and neutralizing Abs against TGF-beta1 can block their
      suppressive activity. We found that CD69(+)CD4(+)CD25(-) T cells express membrane
      bound TGF-beta1, which mediates suppression of T cell proliferation. Furthermore,
      engagement of CD69 maintains high expression of membrane-bound TGF-beta1 on
      CD69(+)CD4(+)CD25(-) T cells via ERK activation. Our results demonstrate that
      CD69(+)CD4(+)CD25(-) T cells act as a new subset of regulatory CD4(+) T cells,
      with distinct characteristics of negative expression of Foxp3, no secretion of IL
      10, but high expression of CD122 and membrane-bound TGF-beta1. Our data
      contribute to the better understanding of mechanisms for tumor immune escape.

PMID- 19109142
TI  - An essential role for the stalk region of CD8 beta in the coreceptor function of
      CD8.
AB  - The CD8alphabeta heterodimer is integral to the selection of the class I
      restricted lineage in the thymus; however, the contribution of the CD8beta chain
      to coreceptor function is poorly understood. To understand whether the CD8beta
      membrane proximal stalk region played a role in coreceptor function, we
      substituted it with the corresponding sequence from the CD8alpha polypeptide and
      expressed the hybrid molecule in transgenic mice in place of endogenous CD8beta.
      Although the stalk-swapped CD8beta was expressed on the cell surface as a
      disulfide-bonded heterodimer at equivalent levels of expression to an endogenous
      CD8beta molecule, it failed to restore selection of CD8(+) class I MHC-restricted
      T cells and it altered the response of peripheral T cells. Thus, the stalk region
      of the CD8beta polypeptide has an essential role in ensuring functionality of the
      CD8alphabeta heterodimer and its replacement compromises the interaction of CD8
      with peptide-MHC complexes.

PMID- 19109143
TI  - Checkpoints in the development of thymic cortical epithelial cells.
AB  - In the thymus, interactions between immature thymocytes and thymic epithelial
      cells (TECs) regulate the development and selection of self-tolerant MHC
      restricted T cells. Despite the importance of cortical (cTEC) and medullary
      (mTEC) thymic epithelial cells in fostering T cell production, events in TEC
      development are still unclear. Although precursor-product relationships during
      mTEC development have been reported, and some genetic regulators of mTEC
      development have been identified, stages in cTEC development occurring downstream
      of recently identified bipotent cTEC/mTEC progenitors remain poorly defined. In
      this study, we combine analysis of differentiation, proliferation, and gene
      expression of TECs in the murine thymus, that has enabled us to identify cTEC
      progenitors, define multiple stages in cTEC development, and identify novel
      checkpoints in development of the cTEC lineage. We show an essential requirement
      for FoxN1 in the initial development of cTEC from bipotent progenitors, and
      demonstrate a stage-specific requirement for CD4(-)8(-) thymocytes in later
      stages of cTEC development. Collectively, our data establish a program of cTEC
      development that should provide insight into the formation and function of the
      thymic cortex for T cell development.

PMID- 19109144
TI  - Deviation of the B cell pathway in senescent mice is associated with reduced
      surrogate light chain expression and altered immature B cell generation,
      phenotype, and light chain expression.
AB  - B lymphopoiesis in aged mice is characterized by reduced B cell precursors and an
      altered Ab repertoire. This likely results, in part, from reduced surrogate L
      chains in senescent B cell precursors and compromised pre-BCR checkpoints.
      Herein, we show that aged mice maintain an ordinarily minor pool of early c
      kit(+) pre-B cells, indicative of poor pre-BCR expression, even as pre-BCR
      competent early pre-B cells are significantly reduced. Therefore, in aged mice,
      B2 B lymphopoiesis shifts from dependency on pre-BCR expansion and selection to
      more pre-BCR-deficient pathways. B2 c-kit(+) B cell precursors, from either young
      or aged mice, generate new B cells in vitro that are biased to larger size,
      higher levels of CD43, and decreased kappa L chain expression. Notably, immature
      B cells in aged bone marrow exhibit a similar phenotype in vivo. We hypothesize
      that reduced surrogate L chain expression contributes to decreased pre-B cells in
      aged mice. The B2 pathway is partially blocked with limited B cell development
      and reduced pre-BCR expression and signaling. In old age, B2 pathways have
      limited surrogate L chain and increasingly generate new B cells with altered
      phenotype and L chain expression.

PMID- 19109145
TI  - Levels of Foxp3 in regulatory T cells reflect their functional status in
      transplantation.
AB  - Foxp3 expressing CD4(+)CD25(+) regulatory T cells (Tregs) have been shown to
      prevent allograft rejection in clinical and animal models of transplantation.
      However, the role of Foxp3 in regulating Treg function, and the kinetics and
      mechanism of action of Tregs in inducing allograft tolerance in transplantation,
      are still not fully understood. Thus, we investigated the kinetics and function
      of Tregs in a mouse model of orthotopic corneal transplantation, the most common
      form of tissue grafting worldwide. In this study, using in vitro functional
      assays and in vivo Treg adoptive transfer assays, we show that far more relevant
      than Treg frequency is their level of Foxp3 expression, which is directly
      associated with the potential of Tregs to prevent allograft rejection by
      producing regulatory cytokines and suppressing effector T cell activation. In
      addition, our data clearly demonstrate that Tregs primarily suppress the
      induction of alloimmunity in regional draining lymph nodes rather than
      suppressing the effector phase of the immune response in the periphery. These
      findings provide new insights on Treg dynamics in transplantation, which are
      crucial for designing therapeutic strategies to modulate Treg function and to
      optimize Treg-based cell therapies for clinical translation.

PMID- 19109147
TI  - Alpha beta T cell receptor transfer to gamma delta T cells generates functional
      effector cells without mixed TCR dimers in vivo.
AB  - The successful application of T cell-based immunotherapeutic applications depends
      on the availability of large numbers of T cells with the desired Ag specificity
      and phenotypic characteristics. Engineering of TCR-transferred T lymphocytes is
      an attractive strategy to obtain sufficient T cells with an Ag specificity of
      choice. However, the introduction of additional TCR chains into T cells leads to
      the generation of T cells with unknown specificity, due to the formation of mixed
      dimers between the endogenous and introduced TCR chains. The formation of such
      potentially autoaggressive T cells may be prevented by using gammadelta T cells
      as recipient cells, but the in vivo activity of such TCR-engineered gammadelta T
      cells has not been established. In the present study, we have investigated the in
      vivo functionality of TCR-transduced gammadelta T cells, in particular their Ag
      specific proliferative capacity, Ag specific reactivity, in vivo persistence, and
      their capacity to mount recall responses. The results demonstrate that alphabeta
      TCR engineering of gammadelta T cells forms a feasible strategy to generate Ag
      specific effector T cells that do not express mixed TCR dimers. In view of
      increasing concerns on the potential autoimmune consequences of mixed TCR dimer
      formation, the testing of alphabeta TCR engineered gammadelta T cells in clinical
      trials seems warranted.

PMID- 19109149
TI  - Ly49D engagement on T lymphocytes induces TCR-independent activation and CD8
      effector functions that control tumor growth.
AB  - Recent data showing expression of activating NK receptors (NKR) by conventional T
      lymphocytes raise the question of their role in the triggering of TCR-independent
      responses that could be damaging for the host. Transgenic mice expressing the
      activating receptor Ly49D/DAP12 offer the opportunity to better understand the
      relevance of ITAM signaling in the biology of T cells. In vitro experiments
      showed that Ly49D engagement on T lymphocytes by a cognate MHC class I ligand
      expressed by Chinese hamster ovary (CHO) cells or by specific Ab triggered
      cellular activation of both CD4 and CD8 populations with modulation of activation
      markers and cytokine production. The forced expression of the ITAM signaling
      chain DAP12 is mandatory for Ly49D-transgenic T cell activation. In addition,
      Ly49D stimulation induced T lymphocyte proliferation, which was much stronger for
      CD8 T cells. Phenotypic analysis of anti-Ly49D-stimulated CD8 T cells and their
      ability to produce high levels of IFN-gamma and to kill target cells indicate
      that Ly49D ligation generates effector cytotoxic CD8 T cells. Ly49D engagement by
      itself also triggered cytotoxic activity of activated CD8 T cells. Adoptive
      transfer experiments confirmed that Ly49D-transgenic CD8 T cells are able to
      control growth of CHO tumor cells or RMA cells transfected with Hm1-C4, the Ly49D
      ligand normally expressed by CHO. In conclusion, Ly49D engagement on T cells
      leads to T cell activation and to a full range of TCR-independent effector
      functions of CD8 T cells.

PMID- 19109150
TI  - CD4+ Th-APC with acquired peptide/MHC class I and II complexes stimulate type 1
      helper CD4+ and central memory CD8+ T cell responses.
AB  - T cell-T cell Ag presentation is increasingly attracting attention. We previously
      showed that the in vitro OVA-pulsed dendritic cell (DC(OVA))-activated CD4(+) Th
      cells acquired OVA peptide/MHC (pMHC) class I and costimulatory molecules such as
      CD54 and CD80 from DC(OVA) and acted as CD4(+) Th-APC capable of stimulating OVA
      specific CD8(+) CTL responses. In this study, we further applied the OVA-specific
      TCR-transgenic OT I and OT II mice with deficiency of various cytokines or
      costimulatory molecule genes useful for studying the molecular mechanisms
      underlying in Th-APC's stimulatory effect. We demonstrated that DC(OVA)
      stimulated OT II CD4(+) Th-APC also acquired costimulatory molecules such as
      CD40, OX40L, and 4-1BBL and the functional pMHC II complexes by DC(OVA)
      activation. CD4(+) Th-APC with acquired pMHC II and I were capable of stimulating
      CD4(+) Th1 and central memory CD8(+)44(+)CD62L(high)IL-7R(+) T cell responses
      leading to antitumor immunity against OVA-expressing mouse B16 melanoma. Their
      stimulatory effect on CD8(+) CTL responses and antitumor immunity is mediated by
      IL-2 secretion, CD40L, and CD80 signaling and is specifically targeted to CD8(+)
      T cells in vivo via acquired pMHC I. In addition, CD4(+) Th-APC expressing OVA
      specific TCR, FasL, and perforin were able to kill DC(OVA) and neighboring Th-APC
      expressing endogenous and acquired pMHC II. Taken together, we show that CD4(+)
      Th-APC can modulate immune responses by stimulating CD4(+) Th1 and central memory
      CD8(+) T cell responses and eliminating DC(OVA) and neighboring Th-APC.
      Therefore, our findings may have great impacts in not only the antitumor
      immunity, but also the regulatory T cell-dependent immune tolerance in vivo.

PMID- 19109146
TI  - TCR mu recombination and transcription relative to the conventional TCR during
      postnatal development in opossums.
AB  - Marsupials are a distinct lineage of mammals notable for giving birth to highly
      altricial (relatively less developed) young. The recent discovery of a unique TCR
      chain in marsupials, TCRmu, raises questions about its possible role in early
      development. Here we compare the timing of V(D)J recombination and appearance of
      TCRmu transcripts relative to the conventional TCRalpha, beta, gamma, and delta
      mRNA during postnatal development in the opossum. There are two TCRmu transcript
      isoforms, TCRmu1.0 and TCRmu2.0. TCRmu1.0, which uses prejoined V(D)J segments,
      is detectable as early as day 1, when the thymus is primarily undifferentiated
      epithelium. The other isoform, TCRmu2.0, which requires V(D)J recombination and
      contains an unusual double V configuration, is not detectable until day 13 when
      the thymus is histologically mature. Surprisingly, we were able to detect
      TCRalpha, beta, and delta mRNA transcribed from loci that had completed V(D)J
      recombination as early as day 1 as well. At this early age there is apparent
      evidence for preference in the V segments used in the TCRalpha and beta genes. In
      the case of Valpha this preference appears to be associated with position in the
      TCRalpha/delta locus. In Vbeta, however, preference may be due to the use of
      microhomology in the V, D, and J segments. Mature TCRgamma transcripts were not
      detected until day 8, suggesting that, in contrast to eutherian mammals, in the
      opossum alphabeta T cell development precedes gammadelta T cell development. The
      results support that there may be differences in T cell subset development
      between marsupials and placental mammals.

PMID- 19109148
TI  - CCR5 expression levels influence NFAT translocation, IL-2 production, and
      subsequent signaling events during T lymphocyte activation.
AB  - Ligands of CCR5, the major coreceptor of HIV-1, costimulate T lymphocyte
      activation. However, the full impact of CCR5 expression on T cell responses
      remains unknown. Here, we show that compared with CCR5(+/+), T cells from CCR5(-/
      ) mice secrete lower amounts of IL-2, and a similar phenotype is observed in
      humans who lack CCR5 expression (CCR5-Delta32/Delta32 homozygotes) as well as
      after Ab-mediated blockade of CCR5 in human T cells genetically intact for CCR5
      expression. Conversely, overexpression of CCR5 in human T cells results in
      enhanced IL-2 production. CCR5 surface levels correlate positively with IL-2
      protein and mRNA abundance, suggesting that CCR5 affects IL-2 gene regulation.
      Signaling via CCR5 resulted in NFAT transactivation in T cells that was blocked
      by Abs against CCR5 agonists, suggesting a link between CCR5 and downstream
      pathways that influence IL-2 expression. Furthermore, murine T cells lacking CCR5
      had reduced levels of intranuclear NFAT following activation. Accordingly, CCR5
      expression also promoted IL-2-dependent events, including CD25 expression, STAT5
      phosphorylation, and T cell proliferation. We therefore suggest that by
      influencing a NFAT-mediated pathway that regulates IL-2 production and IL-2
      dependent events, CCR5 may play a critical role in T cell responses. In accord
      with our prior inferences from genetic-epidemiologic studies, such CCR5-dependent
      responses might constitute a viral entry-independent mechanism by which CCR5 may
      influence HIV-AIDS pathogenesis.

PMID- 19109151
TI  - A role for cFLIP in B cell proliferation and stress MAPK regulation.
AB  - Fas/Apo-1 signals through the FADD (Fas-associated death domain) adaptor protein,
      which recruits and activates the apical caspase 8 and leads to apoptosis.
      Cellular FLIP (cFLIP) is a homolog of caspase 8 and is also capable of binding to
      FADD. Previous studies suggest that cFLIP could either enhance or inhibit
      apoptosis and lead to NF-kappaB and Erk1/2 activation. Like FADD or caspase 8
      deficiency, a lack of cFLIP disrupts embryogenesis and T cell proliferation. It
      has been demonstrated that B cells lacking either FADD or caspase 8 were
      defective in both Fas-induced apoptosis and TLR-induced proliferation, which
      indicates that these death-inducing proteins have an additional role in
      regulating innate immunity. To analyze the function of cFLIP in B cells,
      conditional deletion of cFLIP was induced by using CD19(Cre). The resulting B
      cell-specific cFLIP-deficient mice were found to have reduced numbers of
      peripheral B cells that were hypersensitive to Fas-induced apoptosis and impaired
      in proliferation induced by TLRs and the BCR. Furthermore, there was aberrant
      expression of costimulatory proteins and activation markers in cFLIP-deficient B
      cells. Whereas LPS-induced activation of NF-kappaB and Erk1/2 appears to be
      unaffected, p38 and Jnk were spontaneously activated and hyperinduced in cFLIP
      deficient B cells. Therefore, these data revealed novel functions of cFLIP in B
      cells.

PMID- 19109152
TI  - Progression of pancreatic adenocarcinoma is significantly impeded with a
      combination of vaccine and COX-2 inhibition.
AB  - With a 5-year survival rate of <5%, pancreatic cancer is one of the most rapidly
      fatal malignancies. Current protocols for the treatment of pancreas cancer are
      not as effective as we desire. In this study, we show that a novel Mucin-1 (MUC1)
      based vaccine in combination with a cyclooxygenase-2 inhibitor (celecoxib), and
      low-dose chemotherapy (gemcitabine) was effective in preventing the progression
      of preneoplastic intraepithelial lesions to invasive pancreatic ductal
      adenocarcinomas. The study was conducted in an appropriate triple transgenic
      model of spontaneous pancreatic cancer induced by the KRAS(G12D) mutation and
      that expresses human MUC1 as a self molecule. The combination treatment elicited
      robust antitumor cellular and humoral immune responses and was associated with
      increased apoptosis in the tumor. The mechanism for the increased immune response
      was attributed to the down-regulation of circulating prostaglandin E(2) and
      indoleamine 2, 3,-dioxygenase enzymatic activity, as well as decreased levels of
      T regulatory and myeloid suppressor cells within the tumor microenvironment. The
      preclinical data provide the rationale to design clinical trials with a
      combination of MUC1-based vaccine, celecoxib, and gemcitabine for the treatment
      of pancreatic cancer.

PMID- 19109153
TI  - IFN-gamma dictates allograft fate via opposing effects on the graft and on
      recipient CD8 T cell responses.
AB  - CD8 T cells are necessary for costimulation blockade-resistant rejection.
      However, the mechanism by which CD8 T cells mediate rejection in the absence of
      major costimulatory signals is poorly understood. IFN-gamma promotes CD8 T cell
      mediated immune responses, but IFN-gamma-deficient mice show early graft loss
      despite costimulation blockade. In contrast, we found that IFN-gamma receptor
      knockout mice show dramatically prolonged graft survival under costimulation
      blockade. To investigate this paradox, we addressed the effects of IFN-gamma on T
      cell alloresponses in vivo independent of the effects of IFN-gamma on graft
      survival. We identified a donor-specific CD8 T cell breakthrough response
      temporally correlated with costimulation blockade-resistant rejection. Neither
      IFN-gamma receptor knockout recipients nor IFN-gamma-deficient recipients showed
      a CD8 breakthrough response. Graft death on IFN-gamma-deficient recipients
      despite costimulation blockade could be explained by the lack of IFN-gamma
      available to act on the graft. Indeed, the presence of IFN-gamma was necessary
      for graft survival on IFN-gamma receptor knockout recipients, as either IFN-gamma
      neutralization or the lack of the IFN-gamma receptor on the graft precipitated
      early graft loss. Thus, IFN-gamma is required both for the recipient to mount a
      donor-specific CD8 T cell response under costimulation blockade as well as for
      the graft to survive after allotransplantation.

PMID- 19109154
TI  - Follistatin-like protein 1 promotes arthritis by up-regulating IFN-gamma.
AB  - Follistatin-like protein-1 (FSTL-1) is a poorly characterized protein that is up
      regulated in the early stage of collagen-induced arthritis and that exacerbates
      arthritis when delivered by gene transfer. The current study was designed to
      determine the mechanism by which FSTL-1 promotes arthritis. FSTL-1 was injected
      into mouse paws, resulting in severe paw swelling associated with up-regulation
      of IFN-gamma transcript and the IFN-gamma-induced chemokine, CXCL10. Mice
      depleted of T cells were protected. A central role for IFN-gamma was confirmed by
      the finding that mice deficient in IFN-gamma failed to exhibit paw swelling in
      response to injection of FSTL-1. Furthermore, IFN-gamma secretion from mouse
      spleen cells exposed to a weak TCR signal was increased 5-fold in the presence of
      FSTL-1. FSTL-1 could be induced by innate immune signals, including TLR4 agonists
      and the arthritogenic cytokine, IL-1beta, via an NFkappaB pathway. Finally, FSTL
      1 was found to be overexpressed in human arthritis and its neutralization
      inhibited murine collagen-induced arthritis and suppressed IFN-gamma and CXCL10
      production in arthritic joints. These findings demonstrate that FSTL-1 plays a
      critical role in arthritis by enhancing IFN-gamma signaling pathways and suggest
      a mechanism by which FSTL-1 bridges innate and adaptive immune responses.

PMID- 19109155
TI  - Cancer-expanded myeloid-derived suppressor cells induce anergy of NK cells
      through membrane-bound TGF-beta 1.
AB  - NK cells, the important effector of innate immunity, play critical roles in the
      antitumor immunity. Myeloid-derived suppressor cells (MDSC), a population of
      CD11b(+)Gr-1(+) myeloid cells expanded dramatically during tumor progression, can
      inhibit T cells and dendritic cells, contributing to tumor immune escape.
      However, regulation of NK cell innate function by MDSC in tumor-bearing host
      needs to be investigated. In this study, we found that the function of NK cells
      from liver and spleen was impaired significantly in all tumor-bearing models,
      indicating the impairment of hepatic NK cell function by tumor is a universal
      phenomenon. Then we prepared the orthotopic liver cancer-bearing mice as tumor
      model to investigate how hepatic NK cells are impaired. We show that down
      regulation of NK cell function is inversely correlated with the marked increase
      of MDSC in liver and spleen. MDSC inhibit cytotoxicity, NKG2D expression, and IFN
      gamma production of NK cells both in vitro and in vivo. After incubation with
      MDSC, NK cells could not be activated to produce IFN-gamma. Furthermore, membrane
      bound TGF-beta1 on MDSC is responsible for MDSC-mediated suppression of NK cells.
      The impaired function of hepatic NK cells in orthotopic liver cancer-bearing mice
      could be restored by depletion of MDSC, but not regulatory T cells. Therefore,
      cancer-expanded MDSC can induce anergy of NK cells via membrane-bound TGF-beta1.
      MDSC, but not regulatory T cells, are main negative regulator of hepatic NK cell
      function in tumor-bearing host. Our study provides new mechanistic explanations
      for tumor immune escape.

PMID- 19109156
TI  - NKG2A inhibits invariant NKT cell activation in hepatic injury.
AB  - Activation of invariant NKT (iNKT) cells in the liver is generally regarded as
      the critical step for Con A-induced hepatitis, and the role of NK cell receptors
      for iNKT cell activation is still controversial. In this study we show that
      blockade of the NKG2A-mediated inhibitory signal with antagonistic anti-NKG2A/C/E
      mAb (20d5) aggravated Con A-induced hepatitis in wild-type, Fas ligand (FasL)
      mutant gld, and IL-4-deficient mice even with NK cell and CD8 T cell depletion,
      but not in perforin-, IFN-gamma-, or IFN-gamma- and perforin-deficient mice.
      Consistently, 20d5 pretreatment augmented serum IFN-gamma levels and perforin
      dependent cytotoxicity of liver mononuclear cells following Con A injection, but
      not their FasL/Fas-dependent cytotoxicity. However, blockade of NKG2A-mediated
      signals during the cytotoxicity effector phase did not augment cytotoxic
      activity. Activated iNKT cells promptly disappeared after Con A injection,
      whereas NK1(-) iNKT cells, which preferentially expressed CD94/NKG2A,
      predominantly remained in the liver. Pretreatment with 20d5 appeared to
      facilitate disappearance of iNKT cells, particularly NK1(-) iNKT cells. Moreover,
      Con A-induced and alpha-galactosylceramide-induced hepatic injury was very severe
      in CD94/NKG2A-deficient DBA/2J mice compared with CD94/NKG2A-intact DBA/2JJcl
      mice. Overall, these results indicated that a NKG2A-mediated signal negatively
      regulates iNKT cell activation and hepatic injury.

PMID- 19109158
TI  - Ctla-4 controls regulatory T cell peripheral homeostasis and is required for
      suppression of pancreatic islet autoimmunity.
AB  - The CTLA-4 pathway is recognized as a major immune inhibitory axis and is a key
      therapeutic target for augmenting antitumor immunity or curbing autoimmunity.
      CTLA-4-deficient mice provide the archetypal example of dysregulated immune
      homeostasis, developing lethal lymphoproliferation with multiorgan inflammation.
      In this study, we show that surprisingly these mice have an enlarged population
      of Foxp3(+) regulatory T cells (Treg). The increase in Treg is associated with
      normal thymic output but enhanced proliferation of Foxp3(+) cells in the
      periphery. We confirmed the effect of CTLA-4 deficiency on the Treg population
      using OVA-specific Treg which develop normally in the absence of CTLA-4, but show
      increased proliferation in response to peripheral self-Ag. Functional analysis
      revealed that Ag-specific Treg lacking CTLA-4 were unable to regulate disease in
      an adoptive transfer model of diabetes. Collectively, these data suggest that the
      proliferation of Treg in the periphery is tuned by CTLA-4 signals and that Treg
      expression of CTLA-4 is required for regulation of pancreas autoimmunity.

PMID- 19109157
TI  - Epigenetic regulation of Foxp3 expression in regulatory T cells by DNA
      methylation.
AB  - Foxp3, a winged-helix family transcription factor, serves as the master switch
      for CD4(+) regulatory T cells (Treg). We identified a unique and evolutionarily
      conserved CpG-rich island of the Foxp3 nonintronic upstream enhancer and
      discovered that a specific site within it was unmethylated in natural Treg
      (nTreg) but heavily methylated in naive CD4(+) T cells, activated CD4(+) T cells,
      and peripheral TGFbeta-induced Treg in which it was bound by DNMT1, DNMT3b,
      MeCP2, and MBD2. Demethylation of this CpG site using the DNA methyltransferase
      inhibitor 5-aza-2'-deoxycytidine (Aza) induced acetylation of histone 3,
      interaction with TIEG1 and Sp1, and resulted in strong and stable induction of
      Foxp3. Conversely, IL-6 resulted in methylation of this site and repression of
      Foxp3 expression. Aza plus TGFbeta-induced Treg resembled nTreg, expressing
      similar receptors, cytokines, and stable suppressive activity. Strong Foxp3
      expression and suppressor activity could be induced in a variety of T cells,
      including human CD4(+)CD25(-) T cells. Epigenetic regulation of Foxp3 can be
      predictably controlled with DNMT inhibitors to generate functional, stable, and
      specific Treg.

PMID- 19109159
TI  - Contribution of direct and cross-presentation to CTL immunity against herpes
      simplex virus 1.
AB  - Dendritic cells (DC), which can be subdivided into different phenotypic and
      functional subsets, play a pivotal role in the generation of cytotoxic T cell
      immunity against viral infections. Understanding the modes of Ag acquisition,
      processing and presentation by DC is essential for the design of effective
      antiviral vaccines. We aimed to assess the contribution of direct vs cross
      presentation for the induction of HSV1-specific CD8(+) T lymphocyte responses in
      mice. Using HSV1 strains expressing fluorescence proteins, we provide evidence
      for the ability of HSV1 to induce viral transcription. Using HSV1-wild-type as
      well as gB- or gH-deficient mutants to either directly inoculate DC or to infect
      target cells, which then were given to DC, we show that DC acquired viral Ag via
      phagocytosis of target cells and via direct inoculation of virus being released
      from target cells. Our study corroborates the function of the CD8(+) DC
      specialized in Ag cross-presentation and confirms this specific feature for Ags
      that these DC acquire directly from HSV1. However, although infection of cross
      presenting DC amplified T cell responses, it was not a requirement for
      presentation of viral Ags, both in vitro and in vivo. Finally, we provide
      evidence that direct presentation did not contribute to the Ag presentation
      capacity of CD8(+) DC after phagocytosis of infected target cells. We conclude
      that cross-presentation is of major importance for the induction of CTL immunity
      in mice.

PMID- 19109160
TI  - Double-stranded RNA and TGF-alpha promote MUC5AC induction in respiratory cells.
AB  - Viral infection is a major trigger for exacerbation of asthma and induces
      overproduction of mucins. We investigated whether dsRNA could amplify the
      induction of mucin by TGF-alpha in human bronchial epithelial cells, as well as
      the molecular mechanisms regulating MUC5AC expression. Human pulmonary
      mucoepidermoid carcinoma (NCI-H292) cells and normal human bronchial epithelial
      cells were exposed to polyinosinic-cytidyric acid (poly(I:C)) and TGF-alpha.
      Then, MUC5AC protein production, mRNA expression, and promoter activity were
      evaluated. Cells were pretreated with a selective inhibitor of ERK, and
      phosphorylation of ERK was examined by Western blotting. Furthermore, the
      expression of MAPK phosphatase 3 (MKP3) mRNA was evaluated and the effect of MKP3
      overexpression was assessed. Poly(I:C) synergistically increased MUC5AC induction
      by TGF-alpha in both NCI-H292 and normal human bronchial epithelial cells. This
      increase was dependent on MUC5AC gene transcription. A MEK1/2 inhibitor (U0126)
      significantly inhibited MUC5AC production. Phosphorylation of ERK was enhanced by
      poly(I:C). TGF-alpha stimulation up-regulated MKP3 mRNA expression, while
      costimulation with poly(I:C) inhibited this up-regulation dose-dependently.
      Enhanced expression of MUC5AC mRNA by poly(I:C) in wild-type cells was completely
      suppressed in cells transfected with the MKP3 expression vector. dsRNA can
      synergistically amplify the induction of MUC5AC mucin by TGF-alpha. This
      synergistic effect on MUC5AC production may be due to enhanced activation of ERK
      through inhibition of MKP3 by poly(I:C).

PMID- 19109161
TI  - Rai acts as a negative regulator of autoimmunity by inhibiting antigen receptor
      signaling and lymphocyte activation.
AB  - Rai (ShcC) belongs to the family of Shc adaptor proteins and is expressed in
      neuronal cells, where it acts as a survival factor activating the PI3K/Akt
      survival pathway. In vivo, Rai protects the brain from ischemic damage. In this
      study, we show that Rai is expressed in T and B lymphocytes. Based on the finding
      that Rai(-/-) mice consistently develop splenomegaly, the role of Rai in
      lymphocyte homeostasis and proliferation was addressed. Surprisingly, as opposed
      to neurons, Rai was found to impair lymphocyte survival. Furthermore, Rai
      deficiency results in a reduction in the frequency of peripheral T cells with a
      concomitant increase in the frequency of B cells. Rai(-/-) lymphocytes display
      enhanced proliferative responses to Ag receptor engagement in vitro, which
      correlates with enhanced signaling by the TCR and BCR, and more robust responses
      to allergen sensitization in vivo. A high proportion of Rai(-/-) mice develop a
      lupus-like autoimmune syndrome characterized by splenomegaly, spontaneous
      peripheral T and B cell activation, autoantibody production, and deposition of
      immune complexes in the kidney glomeruli, resulting in autoimmune
      glomerulonephritis. The data identify Rai as a negative regulator of lymphocyte
      survival and activation and show that loss of this protein results in breaking of
      immunological tolerance and development of systemic autoimmunity.

PMID- 19109162
TI  - Antibodies to MHC class I induce autoimmunity: role in the pathogenesis of
      chronic rejection.
AB  - Alloimmunity to mismatched donor HLA-Ags and autoimmunity to self-Ags have been
      hypothesized to play an important role in immunopathogenesis of chronic rejection
      of transplanted organs. However, it is not known what role, if any, alloimmune
      response plays in inducing autoimmunity. To test whether Ab-developed
      posttransplantation to mismatched donor MHC induces autoimmunity and chronic
      rejection, we developed a murine model wherein anti-MHC class I Abs or control
      (C1.18.4/anti-keratin) were administered intrabronchially into native lungs.
      Animals receiving anti-MHC class I, but not control Abs, developed marked
      cellular infiltration around vessels and bronchiole of lung by day 15, followed
      by epithelial hyperplasia, fibrosis, and occlusion of the distal airways similar
      to chronic rejection following human lung transplantation. Lungs of mice
      receiving anti-MHC class I showed increased expression of chemokines, their
      receptors, and growth factors, and induced IL-17 as well as de novo Abs to self
      Ags, K-alpha1 tubulin, and collagen V. IL-17 neutralization by anti-IL-17
      resulted in reduction of autoantibody and lesions induced by anti-MHC class I
      Abs. Thus, our results indicate that Abs to donor MHC can induce autoimmunity,
      mediated by IL-17, which plays a pivotal role in chronic rejection postlung
      transplantation. Therefore, approaches to prevent autoimmunity should be
      considered for the treatment of chronic rejection postlung transplantation.

PMID- 19109163
TI  - Genome-wide innate immune responses in HIV-1-infected macrophages are preserved
      despite attenuation of the NF-kappa B activation pathway.
AB  - Macrophages contribute to HIV-1 infection at many levels. They provide permissive
      cells at the site of inoculation, augment virus transfer to T cells, generate
      long-lived viral reservoirs, and cause bystander cell apoptosis. A body of
      evidence suggests that the role of macrophages in cellular host defense is also
      compromised by HIV-1 infection. In this respect, macrophages are potent cells of
      the innate immune system that initiate and regulate wide-ranging immunological
      responses. This study focuses on the effect of HIV-1 infection on innate immune
      responses by macrophages at the level of signal transduction, whole genome
      transcriptional profiling, and cytokine secretion. We show that in an ex vivo
      model, M-CSF-differentiated monocyte-derived macrophages uniformly infected with
      replicating CCR5-tropic HIV-1, without cytopathic effect, exhibit selective
      attenuation of the NF-kappaB activation pathway in response to TLR4 and TLR2
      stimulation. However, functional annotation clustering analysis of genome-wide
      transcriptional responses to LPS stimulation suggests substantial preservation of
      gene expression changes at the systems level, with modest attenuation of a subset
      of up-regulated LPS-responsive genes, and no effect on a selection of
      inflammatory cytokine responses at the protein level. These results extend
      existing reports of inhibitory interactions between HIV-1 accessory proteins and
      NF-kappaB signaling pathways, and whole genome expression profiling provides
      comprehensive assessment of the consequent effects on immune response gene
      expression. Unexpectedly, our data suggest innate immune responses are broadly
      preserved with limited exceptions, and pave the way for further study of the
      complex relationship between HIV-1 and immunological pathways within macrophages.

PMID- 19109164
TI  - Btk regulates B cell receptor-mediated antigen processing and presentation by
      controlling actin cytoskeleton dynamics in B cells.
AB  - The high efficiency of Ag processing and presentation by B cells requires Ag
      induced BCR signaling and actin cytoskeleton reorganization, although the
      underlying mechanism for such requirements remains elusive. In this study, we
      identify Bruton's tyrosine kinase (Btk) as a linker connecting BCR signaling to
      actin dynamics and the Ag transport pathway. Using xid mice and a Btk inhibitor,
      we show that BCR engagement increases actin polymerization and Wiskott-Aldrich
      syndrome protein activation in a Btk-dependent manner. Concurrently, we observe
      Btk-dependent increases in the levels of phosphatidylinositide-4,5-bisphosphate
      and phosphorylated Vav upon BCR engagement. The rate of BCR internalization, its
      movement to late endosomes, and efficiency of BCR-mediated Ag processing and
      presentation are significantly reduced in both xid and Btk inhibitor-treated B
      cells. Thus, Btk regulates actin dynamics and Ag transport by activating Wiskott
      Aldrich syndrome protein via Vav and phosphatidylinositides. This represents a
      novel mechanism by which BCR-mediated signaling regulates BCR-mediated Ag
      processing and presentation.

PMID- 19109165
TI  - The peroxisome proliferator-activated receptor gamma agonist rosiglitazone
      ameliorates murine lupus by induction of adiponectin.
AB  - Systemic lupus erythematosus (SLE) is an inflammatory autoimmune disease for
      which current therapy is suboptimal. SLE is characterized by autoantibody
      production, with renal disease and premature atherosclerosis being common and
      severe manifestations causing appreciable morbidity and mortality. Peroxisome
      proliferator-activated receptor gamma (PPARgamma) agonists are widely used in the
      treatment of diabetes mellitus for their insulin-sensitizing properties, but also
      have immunomodulatory effects. In this report, we show that the PPARgamma agonist
      rosiglitazone reduces autoantibody production, renal disease, and atherosclerosis
      in mouse models of SLE. The beneficial effect of rosiglitazone on SLE
      manifestations depends on the induction of adiponectin, because rosiglitazone has
      no effect on autoantibody production or renal disease in lupus mice that lack
      adiponectin. In addition, lupus mice that lack adiponectin develop more severe
      disease than adiponectin-sufficient lupus mice, indicating that endogenous
      adiponectin is involved in regulating disease activity. Furthermore,
      administration of exogenous adiponectin ameliorates disease. These experiments
      suggest that PPARgamma agonists may be useful agents for the treatment of SLE.
      They also demonstrate that induction of adiponectin is a major mechanism
      underlying the immunomodulatory effects of PPARgamma agonists.

PMID- 19109167
TI  - IL-3 inhibits TNF-alpha-induced bone resorption and prevents inflammatory
      arthritis.
AB  - IL-3, a cytokine secreted by activated T cells is well known to regulate the
      proliferation, differentiation, and survival of pluripotent hematopoietic stem
      cells. IL-3 functions as a link between the immune and the hematopoietic system.
      In this study, we suggest an important new role of IL-3 in inhibition of TNF
      alpha-induced bone resorption in vitro and prevention of inflammatory arthritis
      in mice. We show here that IL-3 potently and irreversibly inhibits TNF-alpha
      induced bone resorption in hematopoietic precursors of monocyte/macrophage
      lineage. IL-3 showed an inhibitory effect on TNF-alpha-induced bone resorption
      even in the presence of proinflammatory cytokines such as IL-1alpha, TGF-beta(1),
      TGF-beta(3), IL-6, and PGE(2). We found that IL-3 prevented TNF-alpha-induced c
      fos nuclear translocation and AP-1 DNA-binding activity. Interestingly, IL-3
      pretreatment prevented the development of inflammatory arthritis in mice induced
      by a mixture of anti-type II collagen mAbs and LPS. Furthermore, IL-3 prevented
      cartilage and bone loss in the joints indirectly through inhibition of
      inflammation. Thus, we provide the first evidence that IL-3, a strong regulator
      of hematopoiesis, also plays an important role in inhibition of TNF-alpha-induced
      bone resorption and prevention of inflammatory arthritis in mice.

PMID- 19109166
TI  - Genomic instability resulting from Blm deficiency compromises development,
      maintenance, and function of the B cell lineage.
AB  - The RecQ family helicase BLM is critically involved in the maintenance of genomic
      stability, and BLM mutation causes the heritable disorder Bloom's syndrome.
      Affected individuals suffer from a predisposition to a multitude of cancer types
      and an ill-defined immunodeficiency involving low serum Ab titers. To investigate
      its role in B cell biology, we inactivated murine Blm specifically in B
      lymphocytes in vivo. Numbers of developing B lymphoid cells in the bone marrow
      and mature B cells in the periphery were drastically reduced upon Blm
      inactivation. Of the major peripheral B cell subsets, B1a cells were most
      prominently affected. In the sera of Blm-deficient naive mice, concentrations of
      all Ig isotypes were low, particularly IgG3. Specific IgG Ab responses upon
      immunization were poor and mutant B cells exhibited a generally reduced Ab class
      switch capacity in vitro. We did not find evidence for a crucial role of Blm in
      the mechanism of class switch recombination. However, a modest shift toward
      microhomology-mediated switch junction formation was observed in Blm-deficient B
      cells. Finally, a cohort of p53-deficient, conditional Blm knockout mice revealed
      an increased propensity for B cell lymphoma development. Impaired cell cycle
      progression and survival as well as high rates of chromosomal structural
      abnormalities in mutant B cell blasts were identified as the basis for the
      observed effects. Collectively, our data highlight the importance of BLM
      dependent genome surveillance for B cell immunity by ensuring proper development
      and function of the various B cell subsets while counteracting lymphomagenesis.

PMID- 19109168
TI  - Estradiol increases IL-8 secretion of normal human breast tissue and breast
      cancer in vivo.
AB  - IL-8 or CXCL8 has been associated with tumor angiogenesis, metastasis, and poor
      prognosis in breast cancer. Estrogen is crucial in breast carcinogenesis and
      tumor progression. Whether sex steroids affect IL-8 secretion of normal breast
      tissue or breast cancer is not known. Several cell types in a tissue secrete IL
      8. Hence, regulatory mechanisms of IL-8 need to be investigated in whole tissue.
      We used microdialysis to sample IL-8 in normal human breast tissue in situ in pre
      and postmenopausal women, preoperatively in breast cancers of women, and in
      experimental breast cancer in mice. We found a significant positive correlation
      between IL-8 and estradiol in normal breast tissue and hormone-dependent breast
      cancer in vivo. Ex vivo, estradiol exposure increased the IL-8 secretion of
      normal whole breast tissue in culture. In experimental breast cancer, estradiol
      increased IL-8 whereas the anti-estrogen tamoxifen inhibited the secretion of IL
      8 both in vitro and extracellularly in vivo in tumors of nude mice. An anti-IL-8
      Ab inhibited endothelial cell proliferation induced by cancer cell produced IL-8
      and tumors with low IL-8 levels exhibited decreased angiogenesis. Our results
      strongly suggest that estradiol has a critical role in the regulation of IL-8 in
      normal human breast tissue and human breast cancer. IL-8 may present a novel
      therapeutic target for estrogen driven breast carcinogenesis and tumor
      progression.

PMID- 19109170
TI  - Role of TNF-alpha produced by nonantigen-specific cells in a fulminant hepatitis
      mouse model.
AB  - In previous studies, the mechanisms of acute liver injury and virus exclusion
      have been examined using a model wherein HBsAg-specific CTL are injected into
      HBsAg transgenic (Tg) mice. The importance of the role of TNF-alpha in virus
      exclusion was shown, but its role in liver injury was unclear. We crossed the TNF
      alpha knockout mouse and HBsAg-Tg mouse to establish the HBsAg-Tg/TNF-alpha KO
      mouse, and examined the influence of TNF-alpha on liver injury. The severity of
      liver damage, as determined by serum alanine aminotransferase activity, was
      approximately 100 times greater in HBsAg-Tg/TNF-alpha(+/+) than in HBsAg-Tg/TNF
      alpha(-/-) mice after i.v. administration of 5 x 10(6) CTLs. This liver damage
      reached the peak of its severity within 24-48 h, and was restored 7 days later.
      Histopathological examination showed hepatocellular necrosis and inflammatory
      cell infiltrate 24 h after the CTL injection in HBsAg-Tg/TNF-alpha(+/+) mice but
      not in HBsAg-Tg/TNF-alpha(-/-) mice. The liver damage was fatal for all HBsAg
      Tg/TNF-alpha(+/+) mice that received 1.5 x 10(7) CTLs. In contrast, 1.5 x 10(7)
      CTLs could not kill the HBsAg-Tg/TNF-alpha(-/-) mice. The TNF-alpha production
      level was enhanced after the CTL injection in not only intrahepatic macrophages
      but also other types of mononuclear cells from non-HBsAg-Tg/TNF-alpha(+/+) mice.
      An adoptive transfer examination revealed that severe liver damage occurred in
      HBsAg-Tg/TNF-alpha(-/-) mice that had received mononuclear cells from TNF
      alpha(+/+) mice. In conclusion, the present study provides evidence that TNF
      alpha produced by intrahepatic non-Ag-specific inflammatory cells is critical in
      the development of lethal necroinflammatory liver disease.

PMID- 19109169
TI  - OX40 costimulation prevents allograft acceptance induced by CD40-CD40L blockade.
AB  - Disrupting the CD40-CD40L costimulation pathway promotes allograft acceptance in
      many settings. Herein, we demonstrate that stimulating OX40 overrides cardiac
      allograft acceptance induced by disrupting CD40-CD40L interactions. This effect
      of OX40 stimulation was dependent on CD4(+) T cells, which in turn provided help
      for CD8(+) T cells and B cells. Allograft rejection was associated with donor
      reactive Th1 and Th2 responses and an unconventional granulocytic infiltrate and
      thrombosis of the arteries. Interestingly, OX40 stimulation induced a donor
      reactive IgG class switch in the absence of CD40-CD40L interactions, and the
      timing of OX40 stimulation relative to transplantation affected the isotype of
      donor-reactive Ab produced. Inductive OX40 stimulation induced acute graft
      rejection, which correlated with both IgG1 and IgG2a deposition within the graft.
      Once graft acceptance was established following CD40-CD40L blockade, delayed OX40
      stimulation did not induce acute allograft rejection despite priming of graft
      reactive Th1 and Th2. Rather, chronic rejection was induced, which was
      characterized by IgG1 but not IgG2a deposition within the graft. These studies
      reveal both redundancy and key differences in function among costimulatory
      molecules that manifest in distinct pathologies of allograft rejection. These
      findings may help guide development of therapeutics aimed at promoting graft
      acceptance in transplant recipients.

PMID- 19109171
TI  - Influence of B cell antigen receptor expression level on pathways of B cell
      tolerance induction.
AB  - We have described an Ig-transgenic, autoreactive B cell clonotype that undergoes
      a novel tolerance pathway. Early in development this clonotype expresses average
      BCR levels, but these levels are progressively down-regulated as development
      proceeds efficiently to the mature, follicular compartment. This clonotype does
      not display conventional features of anergy and can be induced to undergo
      apoptosis and receptor editing in in vitro bone marrow cultures, but these
      pathways are not taken in vivo. These data suggested that autoantigen-driven down
      regulation of BCR levels and, hence, avidity for autoantigen allows this
      clonotype to bypass conventional tolerance mechanisms. To test this idea, we
      enforced elevated levels of expression of BCR in this clonotype by making the
      transgenic Igh locus homozygous. This resulted in retarded clonotype development
      and L chain receptor editing in vivo. These data support a pivotal role for
      adaptive, autoantigen-induced adjustment of BCR expression levels in the
      regulation of primary B cell development and tolerance.

PMID- 19109173
TI  - Two structurally different rituximab-specific CD20 mimotope peptides reveal that
      rituximab recognizes two different CD20-associated epitopes.
AB  - Peptide mimotopes of the CD20 epitope recognized by rituximab are useful tools
      for studying this therapeutic mAb's functional properties. We previously
      identified two structurally different peptides that are both effective mimotopes:
      a 7-mer cyclic peptide (Rp15-C) bearing the antigenic motif (a/sNPS) that matches
      170(ANPS)173 of the extracellular loop of CD20, and a 12-mer linear peptide (Rp5
      L) containing the antigenic motif (WPxWLE) lacking sequence homology to CD20. In
      this study, we investigated whether the different structures of Rp15-C and Rp5-L
      reflect the mimicry of the same or different CD20 epitopes recognized by
      rituximab. Using immunochemical methods, we found that, like Rp15-C, Rp5-L mimics
      the raft-associated form of CD20 (by inhibiting rituximab binding to CD20 in
      vitro). Rp5-L and Rp15-C elicit, in immunized mice, anti-CD20 Abs that stain
      CD20+ cells with a punctate pattern similar to that of rituximab. However, only
      anti-Rp5-L Abs recognize denatured CD20. When phage-display peptide libraries
      were panned with anti-Rp5-L, phage clones were enriched that expressed the
      consensus qWPxwL, similar to the antigenic motif (WPxWLE), but not matching
      (a/sNPS). Finally, (WPxWLE) and (ANPS) share some, but not all, contact sites
      within the rituximab Ag-combining site, indicating that (WPxWLE) is not an exact
      replica of Rp15-C (or CD20) (ANPS). Altogether, these results indicate that the
      two structurally different peptides are also conformationally different, and
      suggest that rituximab recognizes two different CD20-associated epitopes.

PMID- 19109172
TI  - E2A acts in cis in G1 phase of cell cycle to promote Ig gene diversification.
AB  - Rearranged Ig genes undergo diversification in sequence and structure initiated
      by the DNA deaminase, activation-induced deaminase. Ig genes must be transcribed
      for diversification to occur, but whether there are additional requirements for
      cis activation has not been established. Here we show, by chromatin
      immunoprecipitation, that the regulatory factor E2A associates with the
      rearranged Ig lambda(R) gene in the chicken DT40 B cell line, which performs
      constitutive Ig gene diversification. By analysis of a DT40 derivative in which
      polymerized lactose operator tags the rearranged lambda(R) gene, we show that E2A
      must function in cis to promote diversification and that stimulation of
      diversification in cis depends on the E2A activation domains. By direct imaging,
      we show that lambda(R)/E2A colocalizations are most prominent in G(1). We further
      show that expression of the E2A antagonist Id1 prevents lambda(R)/E2A
      colocalizations in G(1) and impairs diversification but not transcription of
      lambda(R). Thus, E2A acts in cis to promote Ig gene diversification, and G(1)
      phase is the critical window for E2A action.

PMID- 19109174
TI  - A simple mycobacterial monomycolated glycerol lipid has potent immunostimulatory
      activity.
AB  - It is a long held belief that the strong immunostimulatory activity of the
      Mycobacterium bovis bacillus Calmette-Guerin vaccine and Freund's complete
      adjuvant is due to specific mycobacterial cell envelope components, such as
      lipids and polysaccharides. Implicated mycobacterial lipids include, among
      others, the so-called cord factor or trehalose dimycolate, but limited
      information is available regarding the precise molecular nature of the
      stimulatory components responsible for the interaction with human APCs. In this
      regard, the majority of research aimed at identifying and characterizing
      individual immunostimulatory mycobacterial lipids has been performed in the
      murine system using bone marrow-derived dendritic cells. In this study, it is
      documented that potent immunostimulatory activity lies within the bacillus
      Calmette-Guerin nonpolar lipid class. This activity can be narrowed down to a
      remarkably simple monomycolyl glycerol (MMG) with the ability to stimulate human
      dendritic cells as assessed by enhanced expression of activation markers and the
      release of proinflammatory cytokines. A synthetic analog of MMG based on 32
      carbons (C(32)) was found to exhibit comparable levels of immunostimulatory
      activities. Immunization of mice with the tuberculosis vaccine candidate, Ag85B
      ESAT-6, in MMG or the synthetic analog using cationic liposomes as the delivery
      vehicle was found to give rise to a prominent Th1 response characterized by
      significant levels of IFN-gamma. Together, this development opens up the
      possibility of producing a novel class of chemically defined lipid adjuvants to
      enhance the activity of new vaccine formulations, directed against infectious
      agents including tuberculosis.

PMID- 19109176
TI  - Presentation of cytosolically stable peptides by HLA-B27 is not dependent on the
      canonic interactions of N-terminal basic residues in the A pocket.
AB  - HLA-B27 binds peptides with R at position 2. Additionally, a substantial fraction
      of the HLA-B27-bound peptide repertoire has basic residues at position 1. It is
      unclear whether this is determined by structural complementarity with the A
      pocket of the peptide-binding site, by the increased availability of peptides
      with dibasic N-terminal sequences resulting from their cytosolic stability, or
      both. To distinguish between these possibilities two B*2705 mutants were
      generated in which one or two A pocket surface residues stabilizing the peptidic
      R1 side chain were changed: E163T and E163T-W167S. Both mutants bound a large
      fraction of the constitutive peptide repertoire of B*2705. Moreover, 90 B*2705
      ligands of known sequence were examined for their endogenous presentation by the
      mutants. The E163T mutation alone had a limited effect on binding of peptides
      with R1 or K1 and on the relative frequencies of N-terminal residues. However, it
      decreased the overall stability of the molecule. The E163T-W167S mutant also
      bound many of the B*2705 ligands with N-terminal basic residues, but its
      preference for G1 was significantly decreased. The results indicate that the
      capacity of HLA-B27 to bind peptides with N-terminal basic residues is largely
      independent of the canonic interactions that stabilize at least the R1 side
      chain. Thus, the prevalence of HLA-B27 ligands with dibasic N-terminal sequences
      may be significantly influenced by the increased availability of these peptides
      resulting from their cytosolic stability. This confers to HLA-B27 a unique
      capacity to present Ags generated in low amounts, but resistant to intracellular
      degradation.

PMID- 19109175
TI  - MicroRNA-221-222 regulate the cell cycle in mast cells.
AB  - MicroRNAs (miRNAs) constitute a large family of small noncoding RNAs that have
      emerged as key posttranscriptional regulators in a wide variety of organisms.
      Because any one miRNA can potentially regulate expression of a distinct set of
      genes, differential miRNA expression can shape the repertoire of proteins that
      are actually expressed during development and differentiation or disease. Here,
      we have used mast cells as a model to investigate the role of miRNAs in
      differentiated innate immune cells and found that miR-221-222 are significantly
      up-regulated upon mast cell activation. Using both bioinformatics and
      experimental approaches, we identified some signaling pathways, transcription
      factors, and potential cis-regulatory regions that control miR-221-222
      transcription. Overexpression of miR-221-222 in a model mast cell line perturbed
      cell morphology and cell cycle regulation without altering viability. While in
      stimulated cells miR-221-222 partially counteracted expression of the cell-cycle
      inhibitor p27(kip1), we found that in the mouse alternative splicing results in
      two p27(kip1) mRNA isoforms that differ in their 3' untranslated region, only one
      of which is subject to miR-221-222 regulation. Additionally, transgenic
      expression of miR-221-222 from bacterial artificial chromosome clones in
      embryonic stem cells dramatically reduced cell proliferation and severely
      impaired their accumulation. Our study provides further insights on miR-221-222
      transcriptional regulation as well as evidences that miR-221-222 regulate cell
      cycle checkpoints in mast cells in response to acute activation stimuli.

PMID- 19109177
TI  - Residue Lys57 in the collagen-like region of human L-ficolin and its counterpart
      Lys47 in H-ficolin play a key role in the interaction with the mannan-binding
      lectin-associated serine proteases and the collectin receptor calreticulin.
AB  - L- and H-ficolins are serum oligomeric defense proteins consisting of a collagen
      like region and a fibrinogen-like recognition domain that bind to pathogen- and
      apoptotic cell-associated molecular patterns. They share with mannan-binding
      lectin (MBL) the ability to associate with MBL-associated serine proteases (MASP)
      1, -2, -3, and protein MAp19 and to trigger the lectin complement pathway through
      MASP-2 activation. Recent studies have revealed the essential role of Lys(55) in
      the collagenous region of MBL in the interaction with the MASPs and calreticulin
      (CRT). To test the possible involvement of the homologous residues Lys(57) of L
      ficolin and Lys(47) of H-ficolin, point mutants of both proteins were produced in
      which these residues were mutated to Ala, Glu, or Arg. The resulting mutants
      exhibited oligomerization patterns and ligand binding properties similar to those
      of their wild-type counterparts. In contrast, all three mutations strongly
      inhibited the interaction of L- and H-ficolins with MAp19 and MASP-2 and impaired
      the ability of each ficolin to trigger the lectin pathway. In the case of MASP-1
      and MASP-3, replacement of the target Lys residues by Ala or Glu abolished
      interaction, whereas the Lys to Arg mutations had only slight inhibitory effects.
      Likewise, binding of each ficolin to CRT was inhibited by mutation of Lys to Ala
      or Glu, but not to Arg. In conclusion, residues Lys(57) of L-ficolin and Lys(47)
      of H-ficolin are key components of the interaction with the MASPs and CRT,
      providing strong indication that MBL and the ficolins share homologous binding
      sites for both types of proteins.

PMID- 19109178
TI  - CHAC1/MGC4504 is a novel proapoptotic component of the unfolded protein response,
      downstream of the ATF4-ATF3-CHOP cascade.
AB  - To understand pathways mediating the inflammatory responses of human aortic
      endothelial cells to oxidized phospholipids, we previously used a combination of
      genetics and genomics to model a coexpression network encompassing >1000 genes.
      CHAC1 (cation transport regulator-like protein 1), a novel gene regulated by ox
      PAPC (oxidized 1-palmitoyl-2-arachidonyl-sn-3-glycero-phosphorylcholine), was
      identified in a co-regulated group of genes enriched for components of the ATF4
      (activating transcription factor 4) arm of the unfolded protein response pathway.
      Herein, we characterize the role of CHAC1 and validate the network model. We
      first define the activation of CHAC1 mRNA by chemical unfolded protein response
      inducers, but not other cell stressors. We then define activation of CHAC1 by the
      ATF4-ATF3-CHOP (C/EBP homologous protein), and not parallel XBP1 (X box-binding
      protein 1) or ATF6 pathways, using siRNA and/or overexpression plasmids. To
      examine the subset of genes downstream of CHAC1, we used expression microarray
      analysis to identify a list of 227 differentially regulated genes. We validated
      the activation of TNFRSF6B (tumor necrosis factor receptor superfamily, member
      6b), a FASL decoy receptor, in cells treated with CHAC1 small interfering RNA.
      Finally, we showed that CHAC1 overexpression enhanced apoptosis, while CHAC1
      small interfering RNA suppressed apoptosis, as determined by TUNEL, PARP
      (poly(ADP-ribose) polymerase) cleavage, and AIF (apoptosis-inducing factor)
      nuclear translocation.

PMID- 19109179
TI  - Human cytomegalovirus paralyzes macrophage motility through down-regulation of
      chemokine receptors, reorganization of the cytoskeleton, and release of
      macrophage migration inhibitory factor.
AB  - Macrophages contribute to host defense and to the maintenance of immune
      homeostasis. Conversely, they are important targets of human cytomegalovirus
      (HCMV), a herpesvirus that has evolved many strategies to modulate the host
      immune response. Because an efficient macrophage trafficking is required for
      triggering an adequate immune response, we investigated the effects exerted by
      HCMV infection on macrophage migratory properties. By using endotheliotropic
      strains of HCMV, we obtained high rates of productively infected human monocyte
      derived macrophages (MDM). Twenty-four hours after infection, MDM showed reduced
      polar morphology and became unable to migrate in response to inflammatory and
      lymphoid chemokines, bacterial products and growth factors, despite being viable
      and metabolically active. Although chemotactic receptors were only partially
      affected, HCMV induced a dramatic reorganization of the cytoskeleton
      characterized by rupture of the microtubular network, stiffness of the actin
      fibers, and collapse of the podosomes. Furthermore, supernatants harvested from
      infected MDM contained high amounts of macrophage migration inhibitory factor
      (MIF) and were capable to block the migration of neighboring uninfected MDM.
      Because immunodepletion of MIF from the conditioned medium completely restored
      MDM chemotaxis, we could show for the first time a functional role of MIF as an
      inhibitor of macrophage migration in the context of HCMV infection. Our findings
      reveal that HCMV uses different mechanisms to interfere with movement and
      positioning of macrophages, possibly leading to an impairment of antiviral
      responses and to an enhancement of the local inflammation.

PMID- 19109181
TI  - The loss and gain of marginal zone and peritoneal B cells is different in
      response to relapsing fever and Lyme disease Borrelia.
AB  - T cell-independent Abs are protective against Lyme disease and relapsing fever,
      illnesses caused by Borrelia spirochetes with distinct blood-borne phases of
      infection. To understand this protective response, we characterized splenic and
      peritoneal B cell compartments during infection using flow cytometry and
      immunohistochemistry. In the spleen, early after infection, Borrelia crocidurae,
      a relapsing fever species, induced a striking loss of marginal zone (MZ) B cells
      from the MZ, while Borrelia burgdorferi, the agent of Lyme disease, induced the
      expansion of this subset. At the same time, no significant changes were observed
      in follicular B cells in response to either species of Borrelia. In the
      peritoneal cavity, a further loss was demonstrated early in response to B.
      crocidurae in the B1b, B1c, and B2 cell subsets, but B1a cells were not
      significantly altered. The loss of B1c and B2 cells was sustained through
      subsequent peaks of spirochetemia, suggesting these subsets may be important in
      resolving relapsing episodes. In contrast, an early and significant increase in
      peritoneal B1a, B1b, and B1c cells, but not B2 cells, occurred in response to B.
      burgdorferi. Later in the course of infection, both species of Borrelia induced
      the selective expansion of peritoneal B1b cells, suggesting that B1b cells may
      participate in long-lasting immunity to Lyme and relapsing fever spirochetes. Our
      data demonstrate that different Borrelia can activate the same B cell subsets in
      distinct ways and they each elicit a complex interplay of MZ and multiple
      peritoneal B cell subsets in the early response to infection.

PMID- 19109180
TI  - Toxoplasma gondii prevents chromatin remodeling initiated by TLR-triggered
      macrophage activation.
AB  - Macrophages infected with the opportunistic protozoan Toxoplasma gondii are
      unable to up-regulate many proinflammatory cytokine genes, including TNF (TNF
      alpha), upon stimulation with LPS and other TLR ligands. In this study, we
      examined the influence of T. gondii on transcription factors associated with TNF
      alpha transcription, as well as phosphorylation and acetylation of histone H3 at
      distal and proximal regions of the TNF-alpha promoter. During LPS stimulation, we
      found that Toxoplasma blocks nuclear accumulation of transcription factor c-Jun,
      but not that of cAMP response element-binding protein or NF-kappaB. However,
      chromatin immunoprecipitation studies revealed that binding of all of these
      transcription factors to the TNF promoter was decreased by T. gondii infection.
      Furthermore, the parasite blocked LPS-induced Ser(10) phosphorylation and
      Lys(9)/Lys(14) acetylation of histone H3 molecules associated with distal and
      proximal regions of the TNF-alpha promoter. Our results show that Toxoplasma
      inhibits TNF-alpha transcription by interfering with chromatin remodeling events
      required for transcriptional activation at the TNF promoter, revealing a new
      mechanism by which a eukaryotic pathogen incapacitates proinflammatory cytokine
      production during infection.

PMID- 19109182
TI  - Potent and broad-spectrum antimicrobial activity of CXCL14 suggests an immediate
      role in skin infections.
AB  - The skin is constantly exposed to commensal microflora and pathogenic microbes.
      The stratum corneum of the outermost skin layer employs distinct tools such as
      harsh growth conditions and numerous antimicrobial peptides (AMPs) to
      discriminate between beneficial cutaneous microflora and harmful bacteria. How
      the skin deals with microbes that have gained access to the live part of the skin
      as a result of microinjuries is ill defined. In this study, we report that the
      chemokine CXCL14 is a broad-spectrum AMP with killing activity for cutaneous gram
      positive bacteria and Candida albicans as well as the gram-negative
      enterobacterium Escherichia coli. Based on two separate bacteria-killing assays,
      CXCL14 compares favorably with other tested AMPs, including human beta-defensin
      and the chemokine CCL20. Increased salt concentrations and skin-typical pH
      conditions did not abrogate its AMP function. This novel AMP is highly abundant
      in the epidermis and dermis of healthy human skin but is down-modulated under
      conditions of inflammation and disease. We propose that CXCL14 fights bacteria at
      the earliest stage of infection, well before the establishment of inflammation,
      and thus fulfills a unique role in antimicrobial immunity.

PMID- 19109183
TI  - Programmed necrotic cell death induced by complement involves a Bid-dependent
      pathway.
AB  - The membrane attack complex (MAC) of the complement system induces a necrotic
      type cell death. Earlier findings suggested that Bcl-2 protects cells from MAC
      induced necrosis. Here we examined the involvement of Bid, a proapoptotic
      protein, in MAC-induced cytotoxicity. Bid knockout (Bid-/-) mouse embryonic
      fibroblasts (MEF) and primary fibroblasts were damaged by complement but to a
      significantly lower extent than wild-type (WT) fibroblasts. Bid silencing with
      small interfering RNA duplexes led to elevated resistance of mouse fibroblasts,
      human K562, and Jurkat cells to lysis by complement. Bid-/- MEF were also
      resistant to toxic doses of streptolysin O, melittin, and A23187. Analysis of
      complement protein deposition on fibroblasts demonstrated that less complement C3
      and C9 bound to Bid-/- than to WT cells, even though expression of the membrane
      complement inhibitors Crry and CD59 was relatively reduced on Bid-/- cells. Bid
      was rapidly cleaved in WT MEF subjected to lytic doses of MAC. Pretreatment of
      the cells with the pan-caspase inhibitor z-Val-Ala-Asp(OMe)-fluoromethylketone
      reduced Bid cleavage and cell lysis. These results indicate that complement MAC
      activates two cell death pathways, one involving caspases and Bid and one that is
      Bid-independent.

PMID- 19109184
TI  - Activated V gamma 9V delta 2 T cells trigger granulocyte functions via MCP-2
      release.
AB  - Vgamma9Vdelta2 T cells display a broad antimicrobial activity by directly killing
      infected cells and by inducing an effective adaptive immune response. The
      activation of Vgamma9Vdelta2 T cells by aminobisphosphonate drugs such as
      zoledronic acid (ZOL) results in a massive release of cytokines and chemokines
      that may induce a bystander activation of other immune cells. The aim of this
      work was to evaluate the ability of soluble factors released by ZOL-activated
      Vgamma9Vdelta2 T cells to induce granulocyte activation. We showed that soluble
      factors released by ZOL-stimulated Vgamma9Vdelta2 T cells activate granulocytes
      by inducing their chemotaxis, phagocytosis, and alpha-defensins release.
      Proteomic analysis allowed us to identify a number of cytokines and chemokines
      specifically released by activated Vgamma9Vdelta2 T cells. Moreover, MCP-2
      depletion by neutralizing Ab revealed a critical role of this chemokine in
      induction of granulocyte alpha-defensins release. Altogether, these data show a
      Vgamma9Vdelta2-mediated activation of granulocytes through a bystander mechanism,
      and confirm the wide ability of Vgamma9Vdelta2 T-lymphocytes in orchestrating the
      immune response. In conclusion, an immune modulating strategy targeting
      Vgamma9Vdelta2 T cells may represent a key switch to induce an effective and well
      coordinated immune response, and can be proposed as a way to strengthen the
      immune competence during infectious diseases.

PMID- 19109185
TI  - Crosstalk between prostaglandin E2 and leukotriene B4 regulates phagocytosis in
      alveolar macrophages via combinatorial effects on cyclic AMP.
AB  - Eicosanoid lipid mediators, including prostaglandin E(2) (PGE(2)) and
      leukotrienes (LTs) B(4) and D(4), are produced in abundance in the infected lung.
      We have previously demonstrated that individually, PGE(2) suppresses while both
      classes of LTs augment alveolar macrophage (AM) innate immune functions. In this
      study, we sought to more appropriately model the milieu at a site of infection by
      studying the in vitro effects of these lipid mediators on Fc gammaR-mediated
      phagocytosis when they are present in combination. Consistent with their
      individual actions, both LTB(4) and LTD(4) opposed the suppressive effect of
      PGE(2) on phagocytosis, but only LTB(4) did so by mitigating the stimulatory
      effect of PGE(2) on intracellular cAMP production. Unexpectedly, we observed that
      IgG-opsonized targets themselves elicited a dose-dependent reduction in
      intracellular cAMP in AMs, but this was not observed in peritoneal macrophages or
      elicited peritoneal neutrophils; this effect in AMs was completely abolished by
      treatment with the LT synthesis inhibitor AA861, the BLT receptor 1 antagonist CP
      105,696, and the G alpha i inhibitor pertussis toxin. Of two downstream cAMP
      effectors, protein kinase A and exchange protein activated by cAMP, the ability
      of PGE(2) to activate the latter but not the former was abrogated by both LTs
      B(4) and D(4). Taken together, our results indicate that both classes of LTs
      oppose the immune suppressive actions of PGE(2), with the stimulatory actions of
      LTB(4) reflecting combinatorial modulation of intracellular cAMP and those of
      LTD(4) being cAMP independent.

PMID- 19109186
TI  - The bacterial fermentation product butyrate influences epithelial signaling via
      reactive oxygen species-mediated changes in cullin-1 neddylation.
AB  - The human enteric flora plays a significant role in intestinal health and
      disease. Populations of enteric bacteria can inhibit the NF-kappaB pathway by
      blockade of IkappaB-alpha ubiquitination, a process catalyzed by the E3-SCF(beta
      TrCP) ubiquitin ligase. The activity of this ubiquitin ligase is regulated via
      covalent modification of the Cullin-1 subunit by the ubiquitin-like protein
      NEDD8. We previously reported that interaction of viable commensal bacteria with
      mammalian intestinal epithelial cells resulted in a rapid and reversible
      generation of reactive oxygen species (ROS) that modulated neddylation of Cullin
      1 and resulted in suppressive effects on the NF-kappaB pathway. Herein, we
      demonstrate that butyrate and other short chain fatty acids supplemented to model
      human intestinal epithelia in vitro and human tissue ex vivo results in loss of
      neddylated Cul-1 and show that physiological concentrations of butyrate modulate
      the ubiquitination and degradation of a target of the E3- SCF(beta-TrCP)
      ubiquitin ligase, the NF-kappaB inhibitor IkappaB-alpha. Mechanistically, we show
      that physiological concentrations of butyrate induces reactive oxygen species
      that transiently alters the intracellular redox balance and results in
      inactivation of the NEDD8-conjugating enzyme Ubc12 in a manner similar to effects
      mediated by viable bacteria. Because the normal flora produces significant
      amounts of butyrate and other short chain fatty acids, these data provide a
      functional link between a natural product of the intestinal normal flora and
      important epithelial inflammatory and proliferative signaling pathways.

PMID- 19109187
TI  - Toll-like receptor-mediated production of IL-1Ra is negatively regulated by GSK3
      via the MAPK ERK1/2.
AB  - IL-1 receptor antagonist (IL-1Ra), a natural inhibitor of IL-1beta, has been
      shown to regulate the progression of a variety of inflammatory diseases. Although
      experimental studies and clinical trials have demonstrated the importance of IL
      1Ra in chronic inflammatory diseases, the cellular mechanisms responsible for
      regulating the endogenous production of IL-1Ra by innate immune cells are
      currently unresolved. In the present study, we identify that glycogen-synthase
      kinase 3 (GSK3) regulates the production of the anti-inflammatory cytokine IL-1Ra
      via its ability to regulate the MAPK ERK1/2 in TLR-stimulated cells. Elucidation
      of the cell-signaling pathway by which GSK3 controlled ERK activity demonstrated
      that GSK3 inhibition resulted in an abrogation in the levels of the inhibitory
      residue serine 71 on Rac1 and increased the ability of Rac1 to interact with and
      activate p21-activated protein kinase. siRNA-mediated knockdown of Rac1
      attenuated the ability of GSK3 inhibition to augment phospho-ERK1/2 levels in LPS
      stimulated immune cells. Moreover, inhibiting the ability of GSK3 to augment
      ERK1/2 activity abrogated enhanced IL-1Ra production by GSK3-inhibited cells. Our
      findings identify that GSK3 negatively regulates the levels of IL-1Ra produced by
      LPS-stimulated innate immune cells.

PMID- 19109188
TI  - Immune complex/Ig negatively regulate TLR4-triggered inflammatory response in
      macrophages through Fc gamma RIIb-dependent PGE2 production.
AB  - Excessive activation of TLR may induce endotoxin shock and inflammatory diseases,
      so the negative regulation of TLR-triggered inflammatory response attracts much
      attention. Nonpathogenic immune complex (IC) and Ig (IC/Ig) have been shown to
      play important roles in the regulation of immune responses and to be therapeutic
      in some kinds of autoimmune diseases. However, the role of IC/Ig in the
      regulation of TLR-triggered inflammatory responses and the underlying mechanisms
      remain to be fully understood. In this study we demonstrate that IC/Ig can
      significantly inhibit LPS-induced secretion of TNF-alpha and IL-6 from
      macrophages by preferentially inducing PGE(2). Pretreatment of mice with IC can
      protect wild-type mice, but not Fc gammaRIIb(-/-) mice, from lethal endotoxin
      shock, and significantly reduce the levels of serum TNF-alpha and IL-6 in wild
      type mice but not in Fc gammaR IIb(-/-) mice. Furthermore, blockade of PGE(2) by
      celecoxib restores LPS-induced production of TNF-alpha and IL-6 in the presence
      of IC both in vitro and in vivo. Accordingly, blockade of PGE(2) production in
      vivo results in the increased sensitivity of IC-pretreated mice to lethal
      endotoxin shock. Therefore, IC/Ig can negatively regulate TLR4-triggered
      inflammatory response in macrophages through Fc gammaRIIb-dependent PGE(2). In
      addition, our results suggest that down-regulation of NF-kappaB activation and
      TLR4 expression but activation of protein kinase A pathway in macrophages by
      IC/Ig contribute to the negative regulatory process. Thus we provide new manner
      for the immune regulation and mechanistic explanation for nonpathogenic IC/Ig in
      the treatment of inflammatory or autoimmune diseases.

PMID- 19109189
TI  - Inflammatory cytokine production by human neutrophils involves C/EBP
      transcription factors.
AB  - A growing number of neutrophil-derived cytokines have proven to be crucial to
      various inflammatory and immune processes in vivo. Whereas C/EBP (CCAAT/enhancer
      binding protein) transcription factors are important for neutrophil
      differentiation from myeloid precursors, we report herein that they also regulate
      cytokine production in mature neutrophils. All known C/EBP proteins but
      C/EBPgamma are expressed in neutrophils; most isoforms localize to the nucleus,
      except for C/EBPalpha, which is cytoplasmic. Neutrophil stimulation does not
      alter the overall levels, cellular distribution, or turnover of C/EBP proteins;
      it also does not further induce the constitutive DNA-binding activity detected in
      nuclear extracts, consisting of C/EBPbeta and C/EBPepsilon. However, nuclear
      C/EBPbeta is rapidly phosphorylated upon cell stimulation, suggesting that it can
      activate cytokine promoters. Indeed, the transactivation of an IL-8 promoter
      luciferase construct in a human neutrophil-like cell line was impaired when its
      C/EBP or NF-kappaB sites were mutated. Overexpression of a C/EBP repressor also
      impeded IL-8 promoter transactivation, as well as the generation of IL-8, Mip
      1alpha, and Mip-1beta in this cellular model, whereas TNF-alpha generation was
      mostly unaffected. Finally, overexpression of a C/EBPbeta mutant (T235A) as well
      as chromatin immunoprecipitation assays unveiled an important role for this
      residue in cytokine induction. This is the first demonstration that C/EBP factors
      are important regulators of cytokine expression in human neutrophils.

PMID- 19109190
TI  - Interacting neuroendocrine and innate and acquired immune pathways regulate
      neutrophil mobilization from bone marrow following hemorrhagic shock.
AB  - Polymorphonuclear neutrophils (PMN) are critical innate immune effector cells
      that either protect the host or exacerbate organ dysfunction by migrating to
      injured or inflamed tissues. Resuscitated hemorrhagic shock following major
      trauma promotes the development of organ inflammation by priming PMN migration
      and activation in response to a second, often trivial, stimulus (a so-called "two
      hit" phenomenon). PMN mobilization from bone marrow supports a sustained,
      hemorrhagic shock/resuscitation (HS/R)-primed migration of PMN. We addressed the
      role and mechanism of HS/R in regulating PMN egress from bone marrow. We
      demonstrate that HS/R through the alarmin HMGB1 induces IL-23 secretion from
      macrophages in an autocrine and TLR4 signaling-dependent manner. In turn IL-23,
      through an IL-17 G-CSF-mediated mechanism, induces PMN egress from bone marrow.
      We also show that beta-adrenergic receptor activation by catecholamine of
      macrophages mediates the HS/R-induced release of HMGB1. These data indicate that
      HS/R, a global ischemia/reperfusion stimulus, regulates PMN mobilization through
      a series of interacting pathways that include neuroendocrine and innate and
      acquired immune systems. Blocking this novel signaling axis may present a novel
      therapeutic target for posttrauma inflammation.

PMID- 19109192
TI  - IL-10 enhances MD-2 and CD14 expression in monocytes and the proteins are
      increased and correlated in HIV-infected patients.
AB  - Soluble proteins that bind LPS, like myeloid differentiation-2 (MD-2) and CD14,
      have essential roles in regulating LPS signaling through TLR4. During a gram
      negative bacterial infection, the host may control the response by adjusting the
      levels of soluble MD-2 and CD14. To address the surface expression of MD-2 on
      human leukocytes, we developed a mAb, IIC1, that recognized MD-2 both free and
      when bound to TLR4. MD-2 was found on the surface of freshly isolated monocytes,
      on a subpopulation of CD19(+) B-cells and on CD15(+) neutrophils. LPS transiently
      reduced the MD-2 levels on monocytes, which is most likely due to endocytosis of
      the LPS receptor complex since MD-2 colocalized with TLR4 in early endosomes
      after LPS stimulation. In the absence of LPS, MD-2 partly colocalized with TLR4
      in Golgi trans and medial compartments. Cultivating monocytes for 18-20 h
      resulted in loss of MD-2 expression on the surface, which was reversed either by
      LPS or IL-10. Furthermore, addition of IL-10, but not LPS, resulted in a
      considerable increase in mRNA for both MD-2 and CD14. Using ELISA, we
      demonstrated that IL-10 had a profound dose- and time-related effect on the
      release of soluble MD-2 and soluble CD14 from monocytes. In HIV-infected
      patients, the amounts of MD-2, CD14, and IL-10 increased significantly in the
      patient group with AIDS. Of interest, we found that IL-10, CD14, and MD-2 levels
      were positively correlated, suggesting that IL-10 may be a driving force for
      increased release of MD-2 and CD14 during systemic inflammation.

PMID- 19109191
TI  - Milk fat globule epidermal growth factor-factor VIII is down-regulated in sepsis
      via the lipopolysaccharide-CD14 pathway.
AB  - Phagocytosis prevents the release of potentially harmful or immunogenic materials
      from dying cells. Milk fat globule epidermal growth factor (EGF)-factor VIII (MFG
      E8) mediates the clearance of apoptotic cells. We have previously shown that the
      administration of MFG-E8-rich exosomes from immature dendritic cells promotes the
      phagocytosis of apoptotic cells and improves survival in sepsis. Because
      endotoxin is elevated in polymicrobial sepsis, we hypothesized that down
      regulation of MFG-E8 is mediated via the LPS-CD14 pathway, eventually leading to
      the accruement of apoptotic cells. Polymicrobial sepsis was induced by cecal
      ligation and puncture (CLP) in CD14-deficient (CD14(-/-)), TLR4-mutated and wild
      type (WT) mice. In addition, endotoxemia was elicited by i.p. injection of LPS.
      LPS was also neutralized by pretreating CLP-induced WT mice with polymyxin B.
      Splenic MFG-E8 expression, phagocytic activity, and apoptosis were assessed 5 and
      20 h after CLP or 5 h after LPS administration. In septic WT mice, MFG-E8 mRNA
      and protein levels were suppressed by 49 and 33%, respectively. Endotoxemia
      reduced MFG-E8 mRNA expression in a dose dependent manner and the down-regulation
      of MFG-E8 mRNA expression in CLP-induced sepsis was attenuated by polymyxin B.
      This CLP-induced suppression was not observed in both CD14(-/-) and TLR4-mutated
      mice. CLP significantly decreased phagocytic activity of peritoneal macrophages
      in WT (by 30%), but not in CD14(-/-) mice. CLP also induced significant apoptosis
      in the spleen of WT (by 61%), but less in CD14(-/-) mice. Thus, MFG-E8 production
      is down-regulated in sepsis by LPS-CD14 dependent fashion, leading to a reduction
      of phagocytosis of apoptotic cells.

PMID- 19109193
TI  - Potential roles of a special CD8 alpha alpha+ cell population and CC chemokine
      thymus-expressed chemokine in ovulation related inflammation.
AB  - It is well known that ovulation may be an inflammatory process. However, it
      remains elusive how immune cells participate in this process. We have identified
      a novel CD8alpha alpha(+) population, which resembles tissue dendritic cells, in
      the theca of antral follicles. We further observed a dramatic influx of the
      CD8alpha alpha(+) cells into the ovulating follicles. This CD8alpha alpha(+)
      population was absent in the ovary of estradiol-induced anovulatory C31F(1) mice
      and subfertile athymic nude mice. Expression of a CC chemokine thymus-expressed
      chemokine (TECK) has previously been found in the ovary; we further demonstrated
      that TECK attracted CD8alpha alpha(+) cells into the ovary. Anti-TECK Ab,
      elicited in the female mice by active immunization, depleted the ovarian CD8alpha
      alpha(+) cells in vivo. Mice with a high titer of TECK Ab failed to ovulate after
      superovulation induction. More importantly, the immunized mice had greatly
      reduced fertility, which was positively correlated with the Ab titers. Ovarian
      TECK expression was normal in anovulatory C31F(1) mice, suggesting that
      infertility in the immunized mice is due to a block of CD8alpha alpha(+) cell
      migration. Finally, the origin of ovarian CD8alpha alpha(+) cells was explored.
      Upon being transferred, thymic CD8alpha(+) cells were able to home to the theca
      of follicles in the recipients. Thus, ovarian CD8alpha alpha(+) cells, which
      participate in the ovulation-related inflammation, may originate in the thymus.

PMID- 19109194
TI  - Crosstalk between CXCR4/stromal derived factor-1 and VLA-4/VCAM-1 pathways
      regulates neutrophil retention in the bone marrow.
AB  - Neutrophil retention in and release from the bone marrow is a critical process
      that remains incompletely understood. Previous work has implicated the
      CXCR4/stromal derived factor-1 (SDF-1) chemokine axis in the marrow retention of
      neutrophils, yet the adhesion pathways responsible for this retention are
      unknown. Because alpha(4)beta(1) integrin (VLA-4) and its ligand VCAM-1 play a
      central role in the interactions of hematopoietic stem cells, lymphocytes, and
      developing neutrophils in the marrow, we investigated whether this integrin might
      be involved in marrow neutrophil retention and release. In this study, we show
      that VLA-4 is expressed on murine marrow neutrophils and decreases with
      maturation, whereas blockade of this integrin leads to the release of marrow
      neutrophils. Marrow neutrophils adhere via VLA-4 to VCAM-1, which is expressed on
      marrow endothelium and stroma, and inhibition of VCAM-1 causes release of marrow
      neutrophils. Furthermore, SDF-1 (CXCL12) signaling through neutrophil CXCR4
      augments VLA-4 adhesion to VCAM-1 in vitro, an effect that is blocked by
      preincubation with pertussis toxin. In vivo blockade of both CXCR4 and alpha(4)
      causes synergistic release of marrow neutrophils, showing that cross-talk between
      CXCR4 and VLA-4 modulates marrow retention of these cells. Taken together, these
      results indicate that the VLA-4/VCAM adhesion pathway is critical in the
      retention and maturation-controlled release of neutrophils from the marrow, while
      providing an important link between the CXCR4/SDF-1 signaling axis and the
      adhesion events that govern this process.

PMID- 19109195
TI  - Therapeutic targeting of IL-6 trans signaling counteracts STAT3 control of
      experimental inflammatory arthritis.
AB  - Cytokine control of the synovial infiltrate is a central process in the
      development of inflammatory arthritis. In this study, we combine genetic
      approaches and intervention strategies to describe a fundamental requirement for
      IL-6-mediated STAT3 signaling in orchestrating the inflammatory infiltrate in
      monoarticular and systemic models of experimental arthritis. STAT3 activation via
      the common gp130 signal-transducing receptor for all IL-6-related cytokines led
      to increased retention of neutrophils and T cells within the inflamed synovium,
      which included STAT3-regulated IL-17A-secreting T cells. Control of leukocyte
      infiltration was reliant upon IL-6 signaling via its soluble receptor (termed IL
      6 trans signaling), as evidenced by selective blockade of this alternative IL-6
      signaling pathway using an engineered variant of soluble gp130 (sgp130Fc). This
      therapeutic intervention led to substantial clinical improvement in mice with
      emerging or established incidence of systemic arthritis. These data illustrate
      that IL-6 control of STAT3 is critical for regulating the synovial infiltrate in
      inflammatory arthritis, and suggest that selective inhibition of IL-6 trans
      signaling may provide a more refined intervention strategy for blocking IL-6
      driven proarthritic activities.

PMID- 19109196
TI  - CD11b+ myeloid cells are the key mediators of Th2 cell homing into the airway in
      allergic inflammation.
AB  - STAT6-mediated chemokine production in the lung is required for Th2 lymphocyte
      and eosinophil homing into the airways in allergic pulmonary inflammation, and
      thus is a potential therapeutic target in asthma. However, the critical cellular
      source of STAT6-mediated chemokine production has not been defined. In this
      study, we demonstrate that STAT6 in bone marrow-derived myeloid cells was
      sufficient for the production of CCL17, CCL22, CCL11, and CCL24 and for Th2
      lymphocyte and eosinophil recruitment into the allergic airway. In contrast,
      STAT6 in airway-lining cells did not mediate chemokine production or support
      cellular recruitment. Selective depletion of CD11b(+) myeloid cells in the lung
      identified these cells as the critical cellular source for the chemokines CCL17
      and CCL22. These data reveal that CD11b(+) myeloid cells in the lung help
      orchestrate the adaptive immune response in asthma, in part, through the
      production of STAT6-inducible chemokines and the recruitment of Th2 lymphocytes
      into the airway.

PMID- 19109197
TI  - Reciprocal expression and signaling of TLR4 and TLR9 in the pathogenesis and
      treatment of necrotizing enterocolitis.
AB  - Necrotizing enterocolitis (NEC) is a common and often fatal inflammatory disorder
      affecting preterm infants that develops upon interaction of indigenous bacteria
      with the premature intestine. We now demonstrate that the developing mouse
      intestine shows reciprocal patterns of expression of TLR4 and TLR9, the receptor
      for bacterial DNA (CpG-DNA). Using a novel ultrasound-guided in utero injection
      system, we administered LPS directly into the stomachs of early and late
      gestation fetuses to induce TLR4 signaling and demonstrated that TLR4-mediated
      signaling within the developing intestine follows its expression pattern. Murine
      and human NEC were associated with increased intestinal TLR4 and decreased TLR9
      expression, suggesting that reciprocal TLR4 and TLR9 signaling may occur in the
      pathogenesis of NEC. Enteral administration of adenovirus expressing mutant TLR4
      to neonatal mice reduced the severity of NEC and increased TLR9 expression within
      the intestine. Activation of TLR9 with CpG-DNA inhibited LPS-mediated TLR4
      signaling in enterocytes in a mechanism dependent upon the inhibitory molecule
      IRAK-M. Strikingly, TLR9 activation with CpG-DNA significantly reduced NEC
      severity, whereas TLR9-deficient mice exhibited increased NEC severity. Thus, the
      reciprocal nature of TLR4 and TLR9 signaling within the neonatal intestine plays
      a role in the development of NEC and provides novel therapeutic approaches to
      this disease.

PMID- 19109198
TI  - Mast cells contribute to autoimmune inflammatory arthritis via their
      tryptase/heparin complexes.
AB  - Although mast cells (MCs) often are abundant in the synovial tissues of patients
      with rheumatoid arthritis, the contribution of MCs to joint inflammation and
      cartilage loss remains poorly understood. MC-restricted tryptase/heparin
      complexes have proinflammatory activity, and significant amounts of human
      tryptase beta (hTryptase-beta) are present in rheumatoid arthritis synovial
      fluid. Mouse MC protease-6 (mMCP-6) is the ortholog of hTryptase-beta, and this
      serine protease is abundant in the synovium of arthritic mice. We now report that
      C57BL/6 (B6) mice lacking their tryptase/heparin complexes have attenuated
      arthritic responses, with mMCP-6 as the dominant tryptase responsible for
      augmenting neutrophil infiltration in the K/BxN mouse serum-transfer arthritis
      model. While inflammation in this experimental arthritis model was not dependent
      on protease-activated receptor-2, it was dependent on the chemokine receptor
      CXCR2. In support of the latter data, exposure of synovial fibroblasts to
      hTryptase-beta/heparin or mMCP-6/heparin complexes resulted in expression of the
      neutrophil chemotactic factors CXCL1/KC, CXCL5/LIX, and CXCL8/IL-8. Our
      proteomics, histochemistry, and immunohistochemistry data also revealed
      substantial loss of cartilage-derived aggrecan proteoglycans in the arthritic
      joints of wild-type B6 mice but not mMCP-6-null B6 mice. These observations
      demonstrate the functional contribution of MC-restricted tryptase/heparin
      complexes in the K/BxN mouse arthritis model and connect our mouse findings with
      rheumatoid arthritis pathophysiology.

PMID- 19109199
TI  - Th17-polarized immune response in a murine model of hypersensitivity pneumonitis
      and lung fibrosis.
AB  - Hypersensitivity pneumonitis is an environmental lung disease characterized by a
      diffuse mononuclear cell infiltrate in the lung that can progress to pulmonary
      fibrosis with chronic exposure to an inhaled Ag. Using a well-established murine
      model of hypersensitivity pneumonitis, we repeatedly exposed C57BL/6 mice to
      Saccharopolyspora rectivirgula to investigate whether T cells are required for
      lung fibrosis. In the absence of alphabeta T cells, TCRbeta(-/-) mice exposed to
      S. rectivirgula for 4 wk had markedly decreased mononuclear infiltrates and
      collagen deposition in the lung compared with wild-type C57BL/6 mice. In contrast
      to CD8(+) T cells, adoptive transfer of CD4(+) T cells reconstituted the S.
      rectivirgula-induced inflammatory and fibrotic response, suggesting that the
      CD4(+) T cell represents the critical alphabeta T cell subset. Cytokine analysis
      of lung homogenates at various time points after S. rectivirgula exposure failed
      to identify a predominant Th1 or Th2 phenotype. Conversely, IL-17 was found in
      the lung at increasing concentrations with continued exposure to S. rectivirgula.
      Intracellular cytokine staining revealed that 14% of CD4(+) T cells from the lung
      of mice treated with S. rectivirgula expressed IL-17A. In the absence of IL-17
      receptor signaling, Il17ra(-/-) mice had significantly decreased lung
      inflammation and fibrosis compared with wild-type C57BL/6 mice. These data are
      the first to demonstrate an important role for Th17-polarized CD4(+) T
      lymphocytes in the immune response directed against S. rectivirgula in this
      murine model of hypersensitivity pneumonitis and pulmonary fibrosis.

PMID- 19109200
TI  - Citrullination of CXCL12 differentially reduces CXCR4 and CXCR7 binding with loss
      of inflammatory and anti-HIV-1 activity via CXCR4.
AB  - Posttranslational proteolytic processing of chemokines is a natural mechanism to
      regulate inflammation. In this study, we describe modification of the CXC
      chemokine stromal cell-derived factor 1alpha/CXCL12 by peptidylarginine deiminase
      (PAD) that converts arginine residues into citrulline (Cit), thereby reducing the
      number of positive charges. The three NH(2)-terminal arginines of CXCL12, Arg(8),
      Arg(12), and Arg(20), were citrullinated upon incubation with PAD. The
      physiologic relevance of citrullination was demonstrated by showing coexpression
      of CXCL12 and PAD in Crohn's disease. Three CXCL12 isoforms were synthesized for
      biologic characterization: CXCL12-1Cit, CXCL12-3Cit, and CXCL12-5Cit, in which
      Arg(8), Arg(8)/Arg(12)/Arg(20), or all five arginines were citrullinated,
      respectively. Replacement of only Arg(8) caused already impaired (30-fold
      reduction) CXCR4 binding and signaling (calcium mobilization, phosphorylation of
      ERK and protein kinase B) properties. Interaction with CXCR4 was completely
      abolished for CXCL12-3Cit and CXCL12-5Cit. However, the CXCR7-binding capacities
      of CXCL12-1Cit and CXCL12-3Cit were, respectively, intact and reduced, whereas
      CXCL12-5Cit failed to bind CXCR7. In chemotaxis assays with lymphocytes and
      monocytes, CXCL12-3Cit and CXCL12-5Cit were completely devoid of activity,
      whereas CXCL12-1Cit, albeit at higher concentrations than CXCL12, induced
      migration. The antiviral potency of CXCL12-1Cit was reduced compared with CXCL12
      and CXCL12-3Cit and CXCL12-5Cit (maximal dose 200 nM) could not inhibit infection
      of lymphocytic MT-4 cells with the HIV-1 strains NL4.3 and HE. In conclusion,
      modification of CXCL12 by one Cit severely impaired the CXCR4-mediated biologic
      effects of this chemokine and maximally citrullinated CXCL12 was inactive.
      Therefore, PAD is a potent physiologic down-regulator of CXCL12 function.

PMID- 19109202
TI  - Adiponectin and functional adiponectin receptor 1 are expressed by airway
      epithelial cells in chronic obstructive pulmonary disease.
AB  - We screened bronchoalveolar lavage (BAL) fluids from COPD-E (chronic obstructive
      pulmonary disease-Emphysema) and control subjects using a 120 Ab cytokine array
      and demonstrated that adiponectin was highly expressed in BAL in COPD-E. An
      adiponectin ELISA confirmed that adiponectin was highly expressed in BAL in COPD
      E compared with smokers and healthy control subjects. Immunohistochemistry
      studies of lung sections from subjects with COPD-E demonstrated that airway
      epithelial cells expressed significant levels of adiponectin and adiponectin
      receptor (AdipoR) 1 but not AdipoR2. In vitro studies with purified populations
      of human lung A549 epithelial cells demonstrated that they expressed both
      adiponectin and AdipoR1 (but not AdipoR2) as assessed by RT-PCR, Western blot,
      and immunohistochemistry. Lung A549 epithelial AdipoR1were functional as
      incubation with adiponectin induced release of IL-8, which was inhibited by small
      interfering RNA to AdipoR1. Using a mouse model of COPD, tobacco smoke exposure
      induced both evidence of COPD as well as increased levels of adiponectin in BAL
      fluid and increased adiponectin expression by airway epithelial cells. As
      adiponectin expression in adipocytes is dependent upon NF-kappaB we determined
      levels of adiponectin in tobacco smoke exposed CC10-Cre(tg)/Ikkbeta(Delta/Delta)
      mice (deficient in the ability to activate NF-kappaB in airway epithelium). These
      studies demonstrated that CC10-Cre(tg)/Ikkbeta(Delta/Delta) and wild-type mice
      had similar levels of BAL adiponectin and airway epithelial adiponectin
      immunostaining. Overall, these studies demonstrate the novel observation that
      adiponectin and functional AdipoR1are expressed by lung epithelial cells,
      suggesting a potential autocrine and/or paracrine pathway for adiponectin to
      activate epithelial cells in COPD-E.

PMID- 19109203
TI  - Targeting TLR2 attenuates pulmonary inflammation and fibrosis by reversion of
      suppressive immune microenvironment.
AB  - Pulmonary fibrosis is a consequence of chronic lung injury and is associated with
      a high mortality. Despite the pathogenesis of pulmonary fibrosis remaining as an
      enigma, immune responses play a critical role in the deregulation of wound
      healing process after lung injury, which leads to fibrosis. Accumulating evidence
      argues the rationales for current treatments of pulmonary fibrosis using
      immunosuppressive agents such as corticosteroids. In this study, we report that
      bleomycin (BLM), a well-known fibrogenic agent functioning as a TLR2 agonist,
      induced the maturation of dendritic cells and release of cytokines. The BLM
      activation of TLR2 mediated a time-dependent alteration of immune responses in
      the lung. These responses resulted in an increase in the tissue-infiltrating
      proinflammatory cells and cytokines in the early period initially following BLM
      exposure and an increase in the tissue-infiltrating suppressive immune cells and
      factors during the later period following BLM exposure. TLR2 deficiency, however,
      reduced pulmonary inflammation, injury, and subsequently attenuated pulmonary
      fibrosis. Targeting TLR2 by a TLR2-neutralizing Ab not only markedly decreased
      animal death but also protected animals from the development of pulmonary
      fibrosis and reversed the established pulmonary fibrosis through regulating BLM
      induced immunosuppressive microenvironments. Our studies suggest that TLR2 is a
      promising target for the development of therapeutic agents against pulmonary
      fibrosis and that eliminating immunosuppressive cells and factors via
      immunostimulants is a novel strategy for fibro-proliferative diseases. Moreover,
      combining BLM with an anti-TLR2 Ab or TLR2 antagonist for cancer therapy will
      improve the BLM therapeutic profile by enhancing anti-cancer efficacy and
      reducing systemic inflammation and pulmonary fibrosis.

PMID- 19109201
TI  - Heat shock proteins HSP27 and HSP70 are present in the skin and are important
      mediators of allergic contact hypersensitivity.
AB  - Proteomic analysis of murine skin has shown that a variety of heat shock proteins
      (HSPs) are constitutively expressed in the skin. Using murine allergic contact
      hypersensitivity as a model, we investigated the role of two heat shock proteins,
      HSP27 and HSP70, in the induction of cutaneous cell-mediated immune responses.
      Immunohistochemical examination of skin specimens showed that HSP27 was present
      in the epidermis and HSP70 was present in both the epidermis and dermis.
      Inhibition of HSP27 and HSP70 produced a reduction in the 1-fluoro-2,4
      dinitrobenzene contact hypersensitivity response and resulted in the induction of
      Ag-specific unresponsiveness. Treatment of dendritic cell cultures with
      recombinant HSP27 caused in the up-regulation of IL-1beta, TNF-alpha, IL-6, IL
      12p70, and IL-12p40 but not IL-23p19, which was inhibited when Abs to HSP27 were
      added. The 1-fluoro-2,4-dinitrobenzene-conjugated dendritic cells that had been
      treated with HSP27 had an increased capacity to initiate contact hypersensitivity
      responses compared with control dendritic cells. This augmented capacity required
      TLR4 signaling because neither cytokine production by dendritic cells nor the
      increased induction of contact hypersensitivity responses occurred in TLR4
      deficient C3H/HeJ mice. Our findings indicate that a cascade of events occurs
      following initial interaction of hapten with the skin that includes increased
      activity of HSPs, their interaction with TLR4, and, in turn, increased production
      of cytokines that are known to enhance Ag presentation by T cells. The results
      suggest that HSPs form a link between adaptive and innate immunity during the
      early stages of contact hypersensitivity.

PMID- 19109204
TI  - Anti-moesin antibodies in the serum of patients with aplastic anemia stimulate
      peripheral blood mononuclear cells to secrete TNF-alpha and IFN-gamma.
AB  - Moesin is an intracellular protein that links the cell membrane and cytoskeleton,
      while also mediating the formation of microtubules and cell adhesion sites as
      well as ruffling of the cell membrane. To determine the roles of anti-moesin Abs
      derived from the serum of patients with aplastic anemia (AA) in the
      pathophysiology of bone marrow failure, we studied the expression of moesin on
      various blood cells and the effects of anti-moesin Abs on the moesin-expressing
      cells. The proteins recognized by anti-moesin mAbs were detectable on the surface
      of T cells, NK cells, and monocytes from healthy individuals as well as on THP-1
      cells. The peptide mass fingerprinting of the THP-1 cell surface protein and the
      knock-down experiments using short hairpin RNA proved that the protein is moesin
      itself. Both the anti-moesin mAbs and the anti-moesin polyclonal Abs purified
      from the AA patients' sera stimulated THP-1 cells and the PBMCs of healthy
      individuals and AA patients to secrete 60-80% as much TNF-alpha as did LPS 100
      ng/ml. Although the polyclonal Abs induced IFN-gamma secretion from the PBMCs of
      healthy individuals only when the PBMCs were prestimulated by anti-CD3 mAbs, the
      anti-moesin Abs were capable of inducing IFN-gamma secretion from the PBMCs of AA
      patients by themselves. Anti-moesin Abs may therefore indirectly contribute to
      the suppression of hematopoiesis in AA patients by inducing myelosuppressive
      cytokines from immunocompetent cells.

PMID- 19109206
TI  - The CD70/CD27 pathway is critical for stimulation of an effective cytotoxic T
      cell response against B cell precursor acute lymphoblastic leukemia.
AB  - For effective immunotherapy, maintaining the frequency and cytotoxic potential of
      effector cells is critical. In this context costimulation via the CD70/CD27
      pathway has been proven essential. CD70 has been reported to be expressed to
      varying degrees on malignant B cells. However, in B cell precursor acute
      lymphoblastic leukemia, the most common childhood malignancy, the role of CD70 in
      stimulation of antileukemic T cell responses has so far not been delineated.
      Herein we demonstrate that in B cell precursor acute lymphoblastic leukemia
      expression of CD70 is low but can be induced upon blast activation via CD40. Both
      CD70 and CD80/CD86 up-regulated on CD40-stimulated blasts contribute to primary
      stimulation of T cell proliferation and cytokine production in an additive
      manner. These two signals also cooperate in the prevention of T cell anergy. In
      contrast to blockade of CD70 during the effector phase, inhibition of CD70
      mediated costimulation during generation of antileukemic T cells prevents
      effector cell proliferation and reduces their cytotoxic capacity. Modulation of
      the CD70/CD27 pathway may thus represent a novel therapeutic approach for
      augmenting magnitude and quality of the antileukemic response in B cell precursor
      acute lymphoblastic leukemia.

PMID- 19109207
TI  - Probable trimethoprim/sulfamethoxazole-induced higher-level gait disorder and
      nocturnal delirium in an elderly man.
AB  - OBJECTIVE: To report a case of probable trimethoprim/sulfamethoxazole (TMP/SMX)
      induced higher-level gait disorder (HLGD) and nocturnal delirium in an elderly
      patient on high-dose oral therapy. CASE SUMMARY: An 82-year-old man with a recent
      history of depression became comatose following an overdose of escitalopram and
      oxazepam. He was admitted, ventilated for 7 days in the intensive care unit, and
      treated with piperacillin/tazobactam and cefepime for aspiration pneumonia.
      Following discharge to a medical ward, respiratory symptoms persisted and imaging
      confirmed pulmonary abscesses. Stenotrophomonas maltophilia was isolated from
      sputum and, on day 15, TMP/SMX 800 mg/160 mg 1 tablet every 12 hours was
      initiated. On day 35, the dose was increased to 800 mg/160 mg 2 tablets every 12
      hours. By day 37, the patient was unsteady when attempting to stand. From day 40,
      he was noted to have features of HLGD with gait ignition failure, poor balance,
      and frequent falls. His other medications at this time were thiamine 100 mg
      daily, multivitamin 1 tablet daily, omeprazole 20 mg every 12 hours, and modified
      release venlafaxine 150 mg daily. Investigation did not reveal any cause for his
      acute gait disturbance. TMP/SMX was stopped on day 48 and, by day 51, the
      patient's gait had returned to normal. DISCUSSION: Neuropsychiatric adverse
      reactions with TMP/SMX have been infrequently reported. The Naranjo probability
      scale indicated that TMP/SMX was the probable cause of HLGD in this patient.
      CONCLUSIONS: At time of writing, this was the first reported case of HLGD
      associated with TMP/SMX. Clinicians should consider this adverse reaction as a
      potential cause of HLGD, especially in the elderly and those with malnutrition
      and hepatic or renal dysfunction.

PMID- 19109205
TI  - Involvement of the apoptotic mechanism in pemphigus foliaceus autoimmune injury
      of the skin.
AB  - Pemphigus foliaceus (PF) is an organ-specific autoimmune skin disease
      characterized by subcorneal epidermal cell detachment (acantholysis) and
      pathogenic autoantibodies against desmoglein 1. The mechanism responsible for
      pemphigus autoantibody-induced epidermal injury is not fully understood. In this
      study, we used the IgG passive transfer mouse model of PF to investigate the
      relevance of the apoptotic mechanism in pemphigus pathogenesis. TUNEL-positive
      epidermal cells and increased oligonucleosomes in the epidermal cytosolic
      fractions were detected in the diseased mice. Time course study reveals that
      TUNEL-positive epidermal cells appear before intraepidermal blisters. Moreover,
      the proapoptotic factor Bax was up-regulated at the earlier time points (2 and 4
      h), whereas the antiapoptotic factor Bcl-x(L) was down-regulated at the later
      time points (6, 8, and 20 h) post-PF IgG injection by Western blot analysis. The
      active forms of caspase-3 and -6 were detected at the later time period (6, 8,
      and 20 h). Administration of Ac-DEVD-cmk, a peptide-based caspase-3/7 inhibitor,
      protected mice from developing intraepidermal blisters and clinical disease
      induced by PF IgG. The same protective effect was also observed using a broad
      spectrum caspase inhibitor, Bok-D-fmk. Collectively, these findings show that
      biochemical events of apoptosis are provoked in the epidermis of mice injected
      with PF autoantibodies. Caspase activation may contribute to acantholytic blister
      formation in PF.

PMID- 19109208
TI  - Successful use of topiramate in a patient with severe postherpetic neuralgia.
AB  - OBJECTIVE: To describe the case of a patient with postherpetic neuralgia (PHN)
      who had a marked response to topiramate despite failure of several previous
      therapies. CASE SUMMARY: A 79-year-old white male with multiple medical
      comorbidities developed severe trigeminal territory PHN requiring treatment with
      opiates to maintain adequate pain relief. Topiramate was initiated after the
      patient failed treatment with 4 other antiepileptic medications due to various
      adverse events. After 3 months of topiramate therapy, with dosages up to 50 mg
      twice daily, PHN pain had decreased to the point that the patient was able to
      discontinue the use of opiates entirely. At time of writing, he continued to be
      maintained on topiramate 50 mg twice daily with good pain relief and no reported
      adverse effects. DISCUSSION: Topiramate exhibits a number of actions that may
      contribute to the relief of neuropathic pain, including modulation of voltage
      gated sodium and calcium channels, potentiation of gamma-aminobutyric acid
      inhibition, and blockade of alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic
      acid (AMPA)/kainite glutamate receptors. Current evidence-based recommendations
      consider topiramate to be a third-line agent for the treatment of neuropathic
      pain based on studies of its use in painful diabetic neuropathy and chronic
      lumbar radicular pain. A comprehensive search of MEDLINE (1950-August 2008) using
      the terms postherpetic neuralgia, neuralgia, and topiramate revealed only one
      previously published case report evaluating the use of topiramate specifically
      for treatment of PHN. CONCLUSIONS: While it is impossible to determine whether
      pain relief in this case was due to treatment with topiramate as opposed to
      spontaneous resolution of pain over time, this additional case report suggests
      that topiramate may be a useful treatment option for patients with PHN who have
      not responded to or are intolerant of other interventions. Further studies are
      needed to determine whether topiramate should receive a stronger recommendation
      for the treatment of PHN.

PMID- 19109209
TI  - Amiodarone-induced thyrotoxicosis in a patient with autonomously functioning
      nodular goiter.
AB  - OBJECTIVE: To report on adverse reactions associated with amiodarone and
      propylthiouracil. CASE SUMMARY: A 64-year-old female with atrial fibrillation and
      nodular goiter progressed to overt thyrotoxicosis after receiving therapy with
      amiodarone 200 mg/day for less than 12 weeks. Thyroid scan revealed a
      hyperfunctioning nodule in the left lobe, while immunologic studies were negative
      for both thyroid peroxidase and thyroglobulin antibodies. The thyroid-stimulating
      hormone (TSH) receptor antibody level was transiently elevated. Propylthiouracil
      100 mg 3 times/day was started after the withdrawal of amiodarone, but the
      patient developed severe generalized skin rash, fever, and leukocytosis after 4
      weeks. Thyroidectomy was performed, and histopathology was compatible with type 1
      amiodarone-induced thyrotoxicosis (AIT) associated with toxic nodular goiter. An
      objective causality assessment revealed that thyrotoxicosis was probably related
      to use of amiodarone. DISCUSSION: Amiodarone is an antiarrhythmic agent that may
      cause thyroid dysfunction. Differentiating between the 2 types of AIT is
      important for implementation of the correct therapeutic strategy. The transient
      elevation of TSH receptor antibodies in AIT complicated the diagnosis. As a rare
      subtype, type 1 AIT by nodular goiter may be associated with early AIT.
      Initiating thyroid function monitoring within 3 months of amiodarone therapy
      should be considered. CONCLUSIONS: Type 1 AIT caused by nodular goiter is rarely
      reported. Amiodarone should be avoided in such patients and subtotal
      thyroidectomy to remove the toxic nodule may be the treatment of choice.

PMID- 19109210
TI  - Normal pregnancy and healthy child after continued exposure to gliclazide and
      ramipril during pregnancy.
AB  - OBJECTIVE: To report a case of exposure to gliclazide and ramipril during
      pregnancy in a patient with diabetes mellitus and hypertension. CASE SUMMARY: A
      42-year-old female with type 2 diabetes mellitus and hypertension who had been
      taking gliclazide 30 mg/day and ramipril 10 mg/day for 2 years was admitted in
      the 16th week of gestation. The following week, gliclazide and ramipril were
      discontinued and methyldopa 500 mg 4 times daily and intensive insulin therapy
      were instituted. Blood glucose concentrations and blood pressure remained within
      acceptable levels throughout the pregnancy. The patient gave birth to a healthy
      child (3200 g) by cesarean section after completing an uneventful gestation
      period. DISCUSSION: Oral antidiabetic drug use in pregnancy is not recommended
      secondary to known effects on the fetus such as congenital abnormalities, fetal
      hyperinsulinemia, macrosomia, and neonatal hypoglycemia. Although this infant had
      no abnormalities after being exposed to gliclazide and ramipril during the first
      16 weeks of gestation, this case is not an unconditionally acceptable indication
      for safety of these medications in pregnancy. Angiotensin-converting enzyme
      inhibitors increase fetal risks and therefore should not be used during
      pregnancy, according to data from animals and humans. There are few data
      available on use of sulfonylureas; thus, their use should also be avoided during
      pregnancy. CONCLUSIONS: Although the normal pregnancy outcome in our patient does
      not indicate that use of gliclazide and ramipril is safe during gestation, these
      data contribute to limited information regarding human exposure to these drugs.

PMID- 19109211
TI  - Community pharmacists' interventions in asthma care: a descriptive study.
AB  - BACKGROUND: Factors influencing community pharmacists' interventions have been
      identified, but little information is available regarding these factors in asthma
      care. OBJECTIVE: To describe the type and frequency of pharmacists' asthma care
      interventions and to identify factors influencing those interventions. METHODS: A
      pretested, self-administered questionnaire was mailed to all community
      pharmacists registered with the Ordre des pharmaciens du Quebec in 2006. The form
      included questions about the pharmacists' interventions in asthma care in the
      community setting (21 questions), factors influencing the provision of those
      interventions (13 questions), and the responders' characteristics (17 questions).
      RESULTS: A total of 4587 questionnaires were sent; 917 pharmacists returned the
      questionnaires (response rate 20%), and 877 were eligible for analysis. Overall,
      community pharmacists who completed the questionnaire appeared to intervene
      frequently when the initial prescription for asthma medication was filled. About
      98% of responders reported providing verbal information always or often on new
      asthma medication prescriptions. Furthermore, checking for overuse of rescue
      medication and underuse of maintenance therapy always or often was reported by
      91% and 85.8% of responders, respectively. Other interventions at follow-up were
      not as frequently reported. For example, only 8.4% of pharmacists reported
      reassessing inhalation technique always or often. Lack of time was reported to be
      an important barrier to the type and frequency of intervention, while interest on
      the part of the patient appeared to be a significant facilitator. About 99% of
      pharmacists agreed with the statement that they have an important role in asthma
      care. CONCLUSIONS: Community pharmacists appear to intervene with patients with
      asthma mostly at the initiation of treatment, but some interventions at follow-up
      are not frequently done, which could be attributed to organizational factors.

PMID- 19109212
TI  - Perceived advantages and disadvantages of using drug samples in a university
      hospital center: a case study.
AB  - BACKGROUND: The distribution of drug samples is both permitted and a common
      practice in Canada and the US. The impact of this strategy on healthcare workers'
      opinions and habits is a reason for concern. OBJECTIVE: To evaluate the perceived
      advantages and disadvantages of using drug samples in a university hospital
      center. METHOD: An observational, descriptive case study was conducted in a 500
      bed university hospital center between October 18 and November 1, 2007. To obtain
      feedback from the healthcare staff, our research team, which was made up of a
      physician, pharmacy resident, 2 pharmacists, and a student in health
      administration, designed a 26-question survey using a Likert scale (fully agree,
      partially agree, partially disagree, totally disagree, do not know). The
      questions focused on 8 different variables (rapid treatment initiation, free cost
      and availability, practicality of use, patient risk, pharmacist's role, impact on
      choice of treatment, storage and stock management, risk of pilfering). RESULTS:
      In total, 39 physicians, 18 medical residents, 17 medical clerks, 83 nurses, and
      23 pharmacists working in various healthcare units and outpatient clinics (N =
      180) agreed to take part in the survey and fill out the questionnaire. Generally
      speaking, there was a high degree of variation among the professional groups in
      their levels of agreement with the statements on the questionnaire. For example,
      71% of the nurses, 43% of the physicians, 71% of the medical residents, and 36%
      of the medical clerks believed that drug samples encouraged treatment adherence,
      whereas only 17% of the pharmacists were of this opinion. CONCLUSIONS: Our
      results show that the perceived advantages and risks of using drug samples vary
      by healthcare provider group and in terms of exposure or nonexposure to their
      use. Concerned professionals must be provided with this information and strict
      measures must be instituted to ensure patient security.

PMID- 19109213
TI  - Pharmacist involvement in improving asthma outcomes in various healthcare
      settings: 1997 to present.
AB  - OBJECTIVE: To evaluate pharmacists' impact on asthma management outcomes in
      various healthcare settings on the basis of updated guidelines set by the
      National Heart, Lung, and Blood Institute (NHLBI). DATA SOURCES: A search of
      MEDLINE (1997-April 2008) and International Pharmaceutical Abstracts (1997-April
      2008) was conducted using the MeSH terms asthma, community pharmacy services,
      pharmacists, pharmacies, clinic, hospital, disease state management, medication
      therapy management, emergency department, and community. STUDY SELECTION AND DATA
      EXTRACTION: Articles were included if pharmacists participated in the
      intervention and the report measured outcomes of asthma as defined by symptoms,
      pulmonary function, asthma severity, quality of life (QOL), or healthcare
      utilization. DATA SYNTHESIS: Since January 1997, a substantial number of studies
      have been published examining pharmacists' impact on asthma clinical outcomes.
      Twenty-five studies were included in this review: 15 were conducted in community
      pharmacies, 5 in ambulatory clinics, 2 in an in-patient hospital setting, and 3
      as various community initiatives. The studies varied in the type of intervention
      provided and outcomes measured. The most common outcome in community pharmacies
      was pulmonary function measures, in which all but one trial found improvements.
      Half of the community pharmacy trials found improvements in asthma severity, 75%
      found improvements in healthcare utilization, and although some trials found
      improvements in QOL, 2 trials found decreases in QOL. Ambulatory clinics reported
      improvements in asthma symptoms and pulmonary function and decreased healthcare
      utilization. Most trials in the ambulatory care setting reported decreases in QOL
      postintervention. Trials in the hospital setting most often reported decreases in
      healthcare utilization. Limitations of the studies, however, included varying
      definitions of asthma control, methodologies used in the studies, and the lack of
      long-term follow-up. CONCLUSIONS: Future study designs may require larger sample
      size and measure outcomes that better assess disease severity in asthma, such as
      impairment and risk domains. This review supports the National Heart, Lung, and
      Blood Institutes of the National Institutes of Health Expert Panel Report 3
      guidelines in recognizing pharmacists as accessible healthcare practitioners who,
      via patient education and medication management, may help patients with asthma
      attain better control of their disease state.

PMID- 19109214
TI  - CD56 expression in T-cell acute lymphoblastic leukemia is associated with non
      thymic phenotype and resistance to induction therapy but no inferior survival
      after risk-adapted therapy.
AB  - BACKGROUND: Expression of CD56 has been associated with poor prognosis in acute
      myeloid leukemia and aggressive lymphoma. DESIGN AND METHODS: We analyzed the
      impact of CD56 expression in a cohort of 452 newly diagnosed adult T-cell acute
      lymphoblastic leukemia (T-ALL) patients; clinical data were available for 306
      patients. Treatment was according to the GMALL study protocols 06/99 and 07/03
      stipulating stratification into standard (thymic T-ALL) and high risk (pre- and
      mature T-ALL) groups. RESULTS: CD56 expression was detected in 63/452 (13.9%)
      patients. CD56(+) T-ALL were predominantly of non-thymic (pre-T 35%, mature 41%)
      immunophenotypic subtypes, whereas 53% of the CD56(-) cases were thymic T-ALL
      (p=0.00002). CD13, CD33, CD34 and HLA-DR were significantly more frequently
      expressed. A clonal T-cell receptor rearrangement was detected in 22/23 CD56(+)
      ALL. No major clinical differences were observed at presentation. Treatment of
      CD56(+) ALL resulted in a lower rate of complete remissions (70% vs. 88%)
      (p=0.001) and a higher rate of resistant disease (21% vs. 8%) (p=0.004). CD56
      expression had no significant influence on overall (48% vs. 59%) and disease free
      survival (67% vs. 57%) at three years. CONCLUSIONS: CD56 is expressed on a subset
      of adult T-ALL with distinct immunophenotypical features and higher resistance to
      therapy. Most CD56(+) ALL were treated in the high-risk arm of the GMALL study
      protocols owing to their non-thymic phenotype. Thus after risk adapted treatment
      a prognostic impact of CD56 expression was not detectable.

PMID- 19109215
TI  - HLA-identical umbilical cord blood transplantation from a sibling donor in
      juvenile myelomonocytic leukemia.

PMID- 19109216
TI  - Italian Society of Hematology guidelines for thalassemia and non-invasive iron
      measurements.

PMID- 19109217
TI  - Mesenchymal stem cells: the fibroblasts' new clothes?
AB  - Mesenchymal stem cells are adherent stromal cells, initially isolated from the
      bone marrow, characterized by their ability to differentiate into mesenchymal
      tissues such as bone, cartilage and fat. They have also been shown to suppress
      immune responses in vitro. Because of these properties, mesenchymal stem cells
      have recently received a very high profile. Despite the dramatic benefits
      reported in early phase clinical trials, their functions remain poorly
      understood. Particularly, several questions remain concerning the origin of
      mesenchymal stem cells and their relationship to other stromal cells such as
      fibroblasts. Whereas clear gene expression signatures are imprinted in stromal
      cells of different anatomical origins, the anti-proliferative effects of
      mesenchymal stem cells and fibroblasts and their potential to differentiate
      appear to be common features between these two cell types. In this review, we
      summarize recent studies in the context of historical and often neglected stromal
      cell literature, and present the evidence that mesenchymal stem cells and
      fibroblasts share much more in common than previously recognized.

PMID- 19109219
TI  - Effective use of imatinib-mesylate in the treatment of relapsed chronic myeloid
      leukemia after allogeneic transplantation.

PMID- 19109218
TI  - STAT6-mediated suppression of erythropoiesis in an experimental model of malarial
      anemia.
AB  - BACKGROUND: The contribution of pro-inflammatory cytokines to the pathogenesis of
      malarial anemia has been studied extensively but the roles of Th2 cytokines
      remain unknown. Here, we investigated the role of signal transducer and activator
      of transcription (STAT)6-mediated responses in erythropoietic suppression during
      acute malaria infection in mice. DESIGN AND METHODS: Naive and/or erythropoietin
      treated wild-type and STAT6(-/-) mice were infected with Plasmodium chabaudi AS
      (P. chabaudi), and the effects parasitemia, hematologic parameters,
      erythropoietin receptor, TER119, and CD71 expression, in vitro erythropoietin
      stimulated proliferation of splenic erythroid precursors, and serum cytokine
      levels were analyzed. To explore the role of interleukin-4 in STAT6-dependent
      erythropoietic suppression, mice were treated in vivo with a monoclonal antibody
      to interleukin-4 and the effects on parasitemia, hematologic parameters, and
      cytokine levels were analyzed. RESULTS: Infected STAT6(-/-) mice developed
      enhanced reticulocytosis compared to wild-type mice despite higher parasitemia
      and a similar course of anemia. Enhanced reticulocytosis in infected STAT6(-/-)
      mice was associated with an increased frequency of late-stage erythroblasts,
      fewer leukocytes expressing CD71, and increased erythropoietin-stimulated
      proliferation of splenocytes compared to infected wild-type mice. Interleukin-4
      depleted wild-type mice had increased levels of parasitemia and a course of
      reticulocytosis similar to responses observed in infected STAT6(-/-) mice.
      Determination of serum cytokine levels in STAT6(-/-) and wild-type mice depleted
      of interleukin-4 by treatment with mAb revealed significantly lower levels of
      interferon-gamma compared to control wild-type mice during infection.
      CONCLUSIONS: Together, these findings provide evidence for a STAT6-dependent
      mechanism in mediating erythropoietic suppression during acute blood-stage
      malaria and indicate a role for interleukin-4 and possibly interferon-gammain
      STAT6-induced erythropoietic suppression.

PMID- 19109220
TI  - Chlamydia infection causes loss of pacemaker cells and inhibits oocyte transport
      in the mouse oviduct.
AB  - Chlamydia trachomatis is a common sexually transmitted bacterial infection that
      results in health care costs in the United States that exceed $2 billion per
      year. Chlamydia infections cause damage to the oviducts, resulting in ectopic
      pregnancy and tubal factor infertility, but the reasons for defective oviduct
      function are poorly understood. We have investigated the role of oviduct
      contractions in egg transport and found that underlying electrical pacemaker
      activity is responsible for oviduct motility and egg transport. Specialized
      pacemaker cells, referred to as oviduct interstitial cells of Cajal (ICC-OVI),
      are responsible for pacemaker activity. The ICC-OVI, labeled with antibodies to
      KIT protein, form a dense network associated with the smooth muscle cells along
      the entire length of the oviduct. Selective removal of ICC-OVI with KIT
      neutralizing antibody resulted in loss of electrical rhythmicity and loss of
      propulsive contractions of the oviduct. We tested whether infection might
      adversely affect the ICC-OVI. Mice infected with Chlamydia muridarum displayed
      dilation of oviducts, pyosalpinx, and loss of spontaneous contractile activity.
      Morphological inspection showed disruption of ICC-OVI networks, and
      electrophysiological recordings showed loss of intrinsic pacemaker activity
      without change in basal smooth muscle membrane potential. Chlamydia infection
      also was associated with upregulation of NOS2 (iNOS) and PTGS2 (COX II) in
      leukocytes. Loss of ICC-OVI and pacemaker activity causes oviduct pseudo
      obstruction and loss of propulsive contractions for oocytes. This, accompanied by
      retention of oviduct secretions, may contribute to the development of tubal
      factor infertility.

PMID- 19109221
TI  - The molecular signature of spermatogonial stem/progenitor cells in the 6-day-old
      mouse testis.
AB  - To characterize the molecular phenotype of spermatogonial stem cells (SSCs), we
      examined genes that are differentially expressed in the stem/progenitor
      spermatogonia compared to nonstem spermatogonia. We isolated type A spermatogonia
      (stem and nonstem type A) from 6-day-old mice using sedimentation velocity at
      unit gravity and further selected the stem/progenitor cell subpopulation by
      magnetic activated cell sorting with an antibody to GDNF-receptor-alpha-1
      (GFRA1). It has been previously shown that GFRA1 is expressed in SSCs and is
      required for their stemness. The purity of the isolated cells was approximately
      95% to 99% as indicated by immunocytochemistry using anti-GFRA1. Comparison of
      GFRA1-positive and GFRA1-negative spermatogonia by microarray analysis revealed
      99 known genes and 12 uncharacterized transcripts that are overexpressed in the
      former cell population with a >2-fold change. Interestingly, the highest level of
      overexpression was observed for Csf1r, encoding the receptor for macrophage
      colony-stimulating factor (M-CSF, official symbol CSF1), which has a well
      established role in the regulation of myeloid progenitor cells. Analysis of our
      microarray data with a bioinformatics software program (Ingenuity Systems)
      revealed the potential role of various signaling pathways in stem/progenitor
      spermatogonia and suggested a common pathway for GFRA1 and CSF1R that may lead to
      their proliferation. Further investigation to test this hypothesis has shown that
      CSF1 promotes cell proliferation in primary cultures of the isolated type A
      spermatogonia and in the spermatogonial-derived stem cell line C18-4.
      Semiquantitative RT-PCR and immunohistochemistry confirmed the previously
      mentioned microarray data. Collectively, this study provides novel molecular
      signatures for stem/progenitor spermatogonia and demonstrates a role for
      CSF1/CSF1R signaling in regulating their proliferation.

PMID- 19109222
TI  - Prostaglandin F2alpha stimulates 11Beta-hydroxysteroid dehydrogenase 1 enzyme
      bioactivity and protein expression in bovine endometrial stromal cells.
AB  - 11Beta-hydroxysteroid dehydrogenase (HSD11B) enzymes have important roles in
      regulating cortisol availability in target tissues. We previously demonstrated
      that HSD11B1 is expressed and active in bovine endometrium and that cortisol
      suppresses prostaglandin (PG) F2alpha and PGE2 production in cultured bovine
      endometrial stromal cells. The present study was conducted to examine whether
      locally synthesized PGF2alpha and/or PGE2 regulates the enzymatic bioactivity
      and/or the expression of HSD11B1 in bovine endometrium. The conversion rate of
      cortisone to cortisol in cultured endometrial stromal cells was significantly
      stimulated by PGF2alpha (1 and 10 microM). In a dose-dependent manner, PGF2alpha
      but not PGE2 increased the net conversion of cortisone to cortisol in stromal
      cells after 4 h of treatment. In addition, the bioactivity of HSD11B1 was
      significantly inhibited by indomethacin (10 microM). The inhibitory effect of
      indomethacin on HSD11B1 bioactivity was abolished by PGF2alpha (1 microM) but not
      by PGE2. Although PGF2alpha (1 microM) did not affect the expression of HSD11B1
      mRNA in cultured stromal cells, it significantly stimulated the protein
      expression of HSD11B1. Cycloheximide, a general translational inhibitor,
      abolished the stimulatory effects of PGF2alpha on HSD11B1 protein expression in
      endometrial stromal cells, indicating that PGF2alpha increases HSD11B1 protein
      expression by stimulating a posttranscriptional process rather than a
      transcriptional mechanism. These results demonstrate that PGF2alpha but not PGE2
      increases HSD11B1 bioactivity and protein expression by stimulating a
      posttranscriptional mechanism in stromal cells and suggest that cortisol has a
      physiologically relevant role in preventing excessive uterine PG production in
      nonpregnant bovine endometrium.

PMID- 19109223
TI  - Alpha-lipoic acid inhibits tumor necrosis factor-induced remodeling and weakening
      of human fetal membranes.
AB  - Untimely rupture of the fetal membranes (FMs) is a major precipitant of preterm
      birth. Although the mechanism of FM weakening leading to rupture is not
      completely understood, proinflammatory cytokines, including tumor necrosis factor
      (TNF) and interleukin 1 beta (IL1B), have been shown to weaken FMs concomitant
      with the induction of reactive oxygen species, collagen remodeling, and
      prostaglandin release. We hypothesized that alpha-lipoic acid, a dietary
      antioxidant, may block the effect of inflammatory mediators and thereby inhibit
      FM weakening. Full-thickness FM fragments were incubated with control media or
      TNF, with or without alpha-lipoic acid pretreatment. Fetal membrane rupture
      strength and the release of matrix metalloproteinase 9 (MMP9) and prostaglandin
      E(2) (PGE(2)) from the full-thickness FM fragments were determined. The two
      constituent cell populations in amnion, the mechanically strongest FM component,
      were similarly examined. Amnion epithelial and mesenchymal cells were treated
      with TNF or IL1B, with or without alpha-lipoic acid pretreatment. MMP9 and PGE(2)
      were analyzed by ELISA, Western blot, and zymography. TNF decreased FM rupture
      strength 50% while increasing MMP9 and PGE(2) release. Lipoic acid inhibited
      these TNF-induced effects. Lipoic acid pretreatment also inhibited TNF- and IL1B
      induced increases in MMP9 protein activity and release in amnion epithelial
      cells, as well as PGE(2) increases in both amnion epithelial and mesenchymal
      cells. In summary, lipoic acid pretreatment inhibited TNF-induced weakening of FM
      and cytokine-induced MMP9 and PGE(2) in both intact FM and amnion cells. We
      speculate that dietary supplementation with alpha-lipoic acid might prove
      clinically useful in prevention of preterm premature rupture of fetal membranes.

PMID- 19109224
TI  - Mitogen-activated protein kinase signaling in male germ cell apoptosis in the
      rat.
AB  - Programmed germ cell death is critical for functional spermatogenesis. Increased
      germ cell apoptosis can be triggered by various regulatory stimuli, including
      testicular hyperthermia or deprivation of gonadotropins and intratesticular
      testosterone. We have previously shown the involvement of the mitogen-activated
      protein kinase (MAPK) 14 in apoptotic signaling of male germ cells across species
      after hormone deprivation. This study investigates the role of MAPK14 in germ
      cell apoptosis in rats triggered by testicular hyperthermia. The contributions of
      the MAPK1/3 and the MAPK8 to male germ cell death were also examined after this
      intervention. We show that 1) testicular hyperthermia results in induction of
      both MAPK1/3 and MAPK14 but not MAPK8; 2) inhibition of MAPK1/3 has no effect on
      the incidence of heat-induced germ cell apoptosis, suggesting that MAPK1/3
      signaling may be dispensable for heat-induced male germ cell apoptosis; and 3)
      activation of MAPK14 and BCL2 phosphorylation are critical for heat-induced male
      germ cell apoptosis in rats. Thus, unlike the hormone deprivation model, heat
      stress through activation of the MAPK14 signaling promotes germ cell apoptosis by
      provoking BCL2 phosphorylation, leading to its inactivation and the subsequent
      activation of the mitochondria-dependent death pathway. These novel findings
      point to a critical role of MAPK14 in stage- and cell-specific activation of male
      germ cell apoptosis triggered by hormone deprivation or heat stress.

PMID- 19109225
TI  - Etoposide induces TRP53-dependent apoptosis and TRP53-independent cell cycle
      arrest in trophoblasts of the developing mouse placenta.
AB  - Abnormal regulation of placental apoptosis and proliferation has been implicated
      in placental disorders. Recently, several DNA-damaging agents were reported to
      induce excessive apoptosis and reduce cell proliferation in the placenta;
      however, the molecular pathways of these toxic effects on the placenta are
      unclear. The aim of the present study was to determine the involvement of TRP53,
      a tumor suppressor that mediates cellular responses to DNA damage, in the
      induction of apoptosis and cell cycle arrest in the developing placenta. For this
      purpose, we treated pregnant mice on Day 12 of gestation with 10 mg/kg of
      etoposide and 5-Gy gamma irradiation, potent inducers of DNA damage. We found an
      increase in the number of trophoblastic apoptoses 8 and 24 h after etoposide
      injection and 6 and 24 h after irradiation in the placental labyrinth zone. The
      number of mitoses and DNA syntheses in trophoblasts decreased after treatment.
      The accumulation and phosphorylation of TRP53 protein were detected 8 and 6 h
      after etoposide injection and irradiation, respectively. In Trp53-deficient
      placentas, the induction of etoposide-induced trophoblastic apoptosis is
      abrogated, while the reduction of proliferation occurred similarly as in wild
      type placentas. CDC2A, a regulator of G2/M progression, was inactivated by
      phosphorylation after etoposide injection and irradiation, suggesting that the
      cell cycle was arrested at the G2/M border by treatment. Our study demonstrated
      that etoposide injection induced TRP53-dependent apoptosis and TRP53-independent
      cell cycle arrest in labyrinthine trophoblasts, providing insights into the
      molecular pathway of placental disorders.

PMID- 19109226
TI  - Residual DNA methylation at remission is prognostic in adult Philadelphia
      chromosome-negative acute lymphocytic leukemia.
AB  - Pretreatment aberrant DNA methylation patterns are stable at time of relapse in
      acute lymphocytic leukemia (ALL). We hypothesized that the detection of residual
      methylation alterations at the time of morphologic remission may predict for
      worse prognosis. We developed a real-time bisulfite polymerase chain reaction
      assay and analyzed the methylation levels of p73, p15, and p57(KIP2) at the time
      of initial remission in 199 patients with Philadelphia chromosome-negative and
      MLL(-) ALL. Residual p73 methylation was detected in 18 (9.5%) patients, p15 in
      33 (17.4%), and p57(KIP2) in 7 (3.7%); 140 (74%) patients had methylation of 0
      genes and 48 (25%) of more than or equal to 1 gene. In 123 (65%) patients,
      matched pretreatment samples were also studied and compared with remission ones:
      in 82 of those with initial aberrant methylation of at least one gene, 59 (72%)
      had no detectable methylation at remission and 23 (28%) had detectable residual
      methylation. By multivariate analysis, the presence of residual p73 methylation
      was associated with a significant shorter duration of first complete remission
      (hazard ratio=2.68, P= .003) and overall survival (hazard ratio=2.69, P= .002).
      In conclusion, detection of epigenetic alterations allows the identification of
      patients with ALL with standard risk but with poor prognosis.

PMID- 19109227
TI  - Hidden abnormalities and novel classification of t(15;17) acute promyelocytic
      leukemia (APL) based on genomic alterations.
AB  - Acute promyelocytic leukemia (APL) is a hematopoietic malignant disease
      characterized by the chromosomal translocation t(15;17), resulting in the
      formation of the PML-RARA gene. Here, 47 t(15;17) APL samples were analyzed with
      high-density single-nucleotide polymorphism microarray (50-K and 250-K SNP-chips)
      using the new algorithm AsCNAR (allele-specific copy-number analysis using
      anonymous references). Copy-number-neutral loss of heterozygosity (CNN-LOH) was
      identified at chromosomes 10q (3 cases), 11p (3 cases), and 19q (1 case). Twenty
      eight samples (60%) did not have an obvious alteration (normal-copy-number [NC]
      group). Nineteen samples (40%) showed either one or more genomic abnormalities: 8
      samples (17%) had trisomy 8 either with or without an additional duplication,
      deletion, or CNN-LOH (+8 group); and 11 samples (23%) had genomic abnormalities
      without trisomy 8 (other abnormalities group). These chromosomal abnormalities
      were acquired somatic mutations. Interestingly, FLT3-ITD mutations (11/47 cases)
      occurred only in the group with no genomic alteration (NC group). Taken together,
      these results suggest that the pathway of development of APL differs in each
      group: FLT3-ITD, trisomy 8, and other genomic changes. Here, we showed for the
      first time hidden abnormalities and novel disease-related genomic changes in
      t(15;17) APL.

PMID- 19109228
TI  - NOTCH1/FBXW7 mutation identifies a large subgroup with favorable outcome in adult
      T-cell acute lymphoblastic leukemia (T-ALL): a Group for Research on Adult Acute
      Lymphoblastic Leukemia (GRAALL) study.
AB  - Many somatic genetic abnormalities have been identified in T-cell acute
      lymphoblastic leukemia (T-ALL) but each individual abnormality accounts for a
      small proportion of cases; therapeutic stratification consequently still relies
      on classical clinical markers. NOTCH1 and/or FBXW7 mutations both lead to
      activation of the NOTCH1 pathway and are among the most frequent mutations in T
      ALL. We screened 141 adult diagnostic T-ALL samples from patients treated on
      either the Lymphoblastic Acute Leukemia in Adults (LALA)-94 (n = 87) or the
      GRAALL-2003 (n = 54) trials. In 88 cases (62%) there were demonstrated NOTCH1
      mutations (42% heterodimerization [HD], 10% HD+proline glutamate serine threonine
      [PEST], 6% PEST, 2% juxtamembrane mutations, 2% transactivation domain [TAD]) and
      34 cases (24%) had FBXW7 mutations (21 cases had both NOTCH1 and FBXW7
      mutations); 40 cases (28%) were wild type for both. There was no significant
      correlation between NOTCH1 and/or FBXW7 mutations and clinico-biologic features.
      Median event-free survival (EFS) and overall survival (OS) were 36 versus 17
      months (P = .01) and not reached versus 32 months (P = .004) in patients with
      NOTCH1 and/or FBXW7 mutations versus other patients, respectively. Multivariate
      analysis showed that the presence of NOTCH1/FBXW7 mutations was an independent
      good prognostic factor for EFS and OS (P = .02 and P = .01, respectively). These
      data demonstrate that NOTCH1 pathway activation by either NOTCH1 or FBXW7
      mutation identifies a large group of patients with a favorable outcome that could
      justify individual therapeutic stratification for T-ALL.

PMID- 19109229
TI  - Mucosal immune responses to HIV-1 in elite controllers: a potential correlate of
      immune control.
AB  - There exists a unique group of persons who are able to durably control HIV in the
      absence of therapy. The mechanisms of control in these persons remain poorly
      defined. In this study, we examined CD8(+) T-cell responses in blood and rectal
      mucosa from 17 "elite controllers" (viral load < 75 copies/mL), 11 "viremic
      controllers" (75-2000 copies/mL), 14 noncontrollers (> 10,000 copies/mL), and 10
      antiretroviral-treated persons (< 75 copies/mL). Production of interferon-gamma,
      interleukin-2, tumor necrosis factor-alpha, macrophage inflammatory protein-1
      beta, and CD107a by CD8(+) T cells in response to HIV-1 Gag stimulation was
      measured using flow cytometry. Our hypothesis was that "polyfunctional" T cells
      producing multiple antiviral factors would be most abundant in mucosal tissues of
      HIV controllers. Mucosal CD8(+) T-cell responses were significantly stronger and
      more complex in controllers than in antiretroviral-suppressed persons (P =
      .0004). The frequency of 4-function responses in rectal mucosa was higher in
      controllers than in noncontrollers and patients on therapy (P < .0001). Mucosal
      responses in controllers were frequently stronger and more complex than blood
      responses. These findings demonstrate that many controllers mount strong, complex
      HIV-specific T-cell responses in rectal mucosa. These responses may play an
      important role in mucosal immune surveillance, as suggested by their relative
      enrichment among persons who control HIV in the absence of therapy.

PMID- 19109230
TI  - Transplantation of allogeneic T cells alters iron homeostasis in NOD/SCID mice.
AB  - Iron overload is common in patients undergoing allogeneic hematopoietic cell
      transplantation (HCT), but the mechanisms leading to overload are unknown. Here,
      we determined iron levels and the expression of iron regulatory proteins in the
      liver and gut of nonobese diabetic-severe combined immunodeficient (NOD/SCID)
      mice that underwent transplantation with syngeneic (histocompatible) or
      allogeneic (histoincompatible) T lymphocytes. Infusion of histoincompatible T
      cells resulted in a significant rise in serum iron levels and liver iron content.
      Iron deposition was accompanied by hepatocyte injury and intestinal villous
      damage. Feeding of low- or high-iron diet was associated with appropriate
      ferroportin 1 and hepcidin responses in mice given histocompatible T cells,
      whereas mice given histoincompatible T cells showed inappropriate up-regulation
      of duodenal ferroportin 1 and a loss of expression of hepatic hepcidin. These
      findings suggest that alloreactive T cell-dependent signals induced dysregulation
      of intestinal iron absorption, which contributed to liver iron overload after
      HCT.

PMID- 19109231
TI  - The temporal profile of the anti-PF4/heparin immune response.
AB  - The immune response in heparin-induced thrombocytopenia (HIT) is puzzling:
      heparin-naive patients can develop IgG antibodies and clinical HIT as early as
      day 5, and evidence for an anamnestic response on heparin reexposure is lacking.
      We assessed daily serum samples by anti-PF4/heparin enzyme-immunoassay (EIA) in
      patients receiving heparin thromboprophylaxis. Of 435 patients, 56.1% showed an
      increase in EIA optical density (OD) of more than or equal to 15%, with more than
      90% starting between days 4 and 14. After reaching maximum reactivity by days 10
      to 12, ODs declined despite heparin continuation, including in 2 patients with
      clinical HIT. Individual IgG/A/M classes showed identical time of onset (median,
      day 6). Most (58.7%) antibody-positive patients developed all 3 Ig classes; only
      11.3% lacked IgG response. IgG/A/M increase usually occurred simultaneously (+/-
      1 day) with no general tendency for IgM precedence. Consistent with the transient
      immune response, none of the IgG-EIA-positive (OD > 0.5) patients at discharge
      developed clinically evident thrombosis during extended low-molecular-weight
      heparin thromboprophylaxis. The rapid onset of the anti-PF4/heparin immune
      response, its transience, and the simultaneous appearance of antibodies of
      different classes with no IgM precedence suggest short-term activation of B cells
      that have previously undergone Ig-class switching even without previous
      pharmacologic heparin exposure.

PMID- 19109233
TI  - Indian hedgehog (Ihh) both promotes and restricts thymocyte differentiation.
AB  - We show that Indian Hedgehog (Ihh) regulates T-cell development and homeostasis
      in both fetal and adult thymus, controlling thymocyte number. Fetal Ihh(-/-)
      thymi had reduced differentiation to double-positive (DP) cell and reduced cell
      numbers compared with wild-type littermates. Surprisingly, fetal Ihh(+/-) thymi
      had increased thymocyte numbers and proportion of DP cells relative to wild type,
      indicating that Ihh also negatively regulates thymocyte development. In vitro
      treatment of thymus explants with exogenous recombinant Hedgehog protein promoted
      thymocyte development in Ihh(-/-) thymi but inhibited thymocyte development in
      Ihh(+/-), confirming both positive and negative regulatory functions of Ihh.
      Analysis of Rag(-/-)Ihh(+/-) thymi showed that Ihh promotes T-cell development
      before pre-T-cell receptor (pre-TCR) signaling, but negatively regulates T-cell
      development only after pre-TCR signaling has taken place. We show that Ihh is
      most highly expressed by the DP population and that Ihh produced by DP cells
      feeds back to negatively regulate the differentiation and proliferation of their
      double-negative progenitors. Thus, differentiation from double-negative to DP
      cell, and hence the size of the DP population, is dependent on the concentration
      of Ihh in the thymus. Analysis of Ihh conditional knockout and heterozygote adult
      mice showed that Ihh also influences thymocyte number in the adult.

PMID- 19109232
TI  - Successful treatment of canine hemophilia by continuous expression of canine
      FVIIa.
AB  - Continuous expression of activated factor VII (FVIIa) via gene transfer is a
      potential therapeutic approach for hemophilia patients with or without inhibitory
      antibodies to human factor VIII (FVIII) or IX (FIX). Here, we investigate whether
      gene transfer of an engineered canine FVIIa (cFVIIa) transgene can affect
      hemostasis in a canine model of hemophilia, a good predictor of efficacy of
      hemophilia treatments. Purified recombinant cFVIIa exhibited 12-fold higher
      tissue factor-dependent activity than purified recombinant zymogen cFVII.
      Subsequently, we generated a serotype 8 recombinant adeno-associated viral vector
      expressing cFVIIa from a liver-specific promoter. Vector delivery via the portal
      vein in hemophilia A and B dogs was well tolerated, and long-term expression of
      cFVIIa resulted in a shortening of the prothrombin time, partial correction of
      the whole blood clotting time and thromboelastography parameters, and a complete
      absence of spontaneous bleeding episodes. No evidence of hepatotoxicity,
      thrombotic complications, or inhibitory immune response was found. These data
      provide the first evidence for in vivo efficacy and safety of continuously
      expressed FVIIa as a FVIII/FIX-bypassing agent in a large animal model of
      hemophilia, avoiding the risk of inhibitor formation associated with bolus FVIII
      or FIX infusion.

PMID- 19109234
TI  - Signal-activated phospholipase regulation of leukocyte chemotaxis.
AB  - Signal-activated phospholipases are a recent focus of the rapidly growing field
      of lipid signaling. The extent of their impact on the pathways regulating diverse
      cell functions is beginning to be appreciated. A critical step in inflammation is
      the attraction of leukocytes to injured or diseased tissue. Chemotaxis of
      leukocytes, a requisite process for monocyte and neutrophil extravasation from
      the blood into tissues, is a critical step for initiating and maintaining
      inflammation in both acute and chronic settings. Recent studies have identified
      new important and required roles for two signal-activated phospholipases A2
      (PLA2) in regulating chemotaxis. The two intracellular phospholipases, cPLA2alpha
      (Group IVA) and iPLA2beta (Group VIA), act in parallel to provide distinct lipid
      mediators at different intracellular sites that are both required for leukocytes
      to migrate toward the chemokine monocyte chemoattractant protein-1. This review
      will summarize the separate roles of these phospholipases as well as what is
      currently known about the influence of two other classes of intracellular signal
      activated phospholipases, phospholipase C and phospholipase D, in regulating
      chemotaxis in eukaryotic cells, but particularly in human monocytes. The
      contributions of these phospholipases to chemotaxis both in vitro and in vivo
      will be highlighted.

PMID- 19109235
TI  - Beyond microarrays.
AB  - Microarray analysis of RNA expression has been changing the way gene expression
      is assayed, but challenges remain in analyzing the results and interpreting the
      data to gain biologically meaningful mechanistic insights.

PMID- 19109236
TI  - Regulatory T cells: the cunning fox and its clinical application.
AB  - So profound is the potential for regulatory T cells (Tregs) to control unwanted
      immune responses that in 2008 an entire conference was dedicated to them. The
      underlying concept of this conference, "China Tregs 2008," was that unraveling
      the cellular biology of Tregs will lead to important advances for therapies in
      virtually all human disease processes and in transplantation. The master-switch
      of immune regulation is the forkhead transcription factor Foxp3; in mice, Foxp3
      is a sine qua non for regulatory activity. At "China Tregs 2008," the cell
      signaling events leading to the expression of Foxp3 and those events downstream
      were explored together with presentations on how the latest knowledge of the
      biology of Tregs is being translated in the clinic.

PMID- 19109237
TI  - Bursting into the nucleus.
AB  - An increase in extracellular Ca(2+) induces the nuclear localization of the Crz1
      transcription factor and the activation of target genes in yeast. A recent study
      indicates that nuclear entry occurs in short stochastic bursts that are
      unsynchronized within the population of cells. The frequency but not the
      amplitude of the bursts is controlled by Ca(2+). Modulation of the frequency of
      the burst coordinates aspects of expression of Crz target genes.

PMID- 19109238
TI  - Untangling the complex web of IL-4- and IL-13-mediated signaling pathways.
AB  - Unraveling the exact signaling events mediating the distinct functions of the T
      cell-derived cytokines interleukin-4 (IL-4) and IL-13 has been challenging
      because they are structurally similar and share a functional signaling receptor
      chain. A study now proposes a potential molecular mechanism to explain the
      functional differences between IL-4 and IL-13 that involves the ability of IL-4,
      but not IL-13, to effectively activate the insulin receptor substrate-2 (IRS-2)
      signaling cascade through binding to its receptor. A better understanding of the
      interactions of IL-4 and IL-13 with their cognate receptors may facilitate the
      development of therapies without unintended side effects.

PMID- 19109240
TI  - mAKAP compartmentalizes oxygen-dependent control of HIF-1alpha.
AB  - The activity of the transcription factor hypoxia-inducible factor 1alpha (HIF
      1alpha) is increased in response to reduced intracellular oxygen. Enzymes of the
      protein ubiquitin machinery that signal the destruction or stabilization of HIF
      1alpha tightly control this transcriptional response. Here, we show that muscle A
      kinase-anchoring protein (mAKAP) organized ubiquitin E3 ligases that managed the
      stability of HIF-1alpha and optimally positioned it close to its site of action
      inside the nucleus. Functional experiments in cardiomyocytes showed that
      depletion of mAKAP or disruption of its targeting to the perinuclear region
      altered the stability of HIF-1alpha and transcriptional activation of genes
      associated with hypoxia. Thus, we propose that compartmentalization of oxygen
      sensitive signaling components may influence the fidelity and magnitude of the
      hypoxic response.

PMID- 19109241
TI  - Structure and function of the phosphothreonine-specific FHA domain.
AB  - The forkhead-associated (FHA) domain is the only known phosphoprotein-binding
      domain that specifically recognizes phosphothreonine (pThr) residues,
      distinguishing them from phosphoserine (pSer) residues. In contrast to its very
      strict specificity toward pThr, the FHA domain recognizes very diverse patterns
      in the residues surrounding the pThr residue. For example, the FHA domain of
      Ki67, a protein associated with cellular proliferation, binds to an extended
      target surface involving residues remote from the pThr, whereas the FHA domain of
      Dun1, a DNA damage-response kinase, specifically recognizes a doubly
      phosphorylated Thr-Gln (TQ) cluster by virtue of its possessing two pThr-binding
      sites. The FHA domain exists in various proteins with diverse functions and is
      particularly prevalent among proteins involved in the DNA damage response.
      Despite a very short history, a number of unique structural and functional
      properties of the FHA domain have been uncovered. This review highlights the
      diversity of biological functions of the FHA domain-containing proteins and the
      structural bases for the novel binding specificities and multiple binding modes
      of FHA domains.

PMID- 19109239
TI  - Type I IL-4Rs selectively activate IRS-2 to induce target gene expression in
      macrophages.
AB  - Although interleukin-4 (IL-4) and IL-13 participate in allergic inflammation and
      share a receptor subunit (IL-4Ralpha), they have different functions. We compared
      cells expressing type I and II IL-4Rs with cells expressing only type II
      receptors for their responsiveness to these cytokines. IL-4 induced highly
      efficient, gammaC-dependent tyrosine phosphorylation of insulin receptor
      substrate 2 (IRS-2), whereas IL-13 was less effective, even when phosphorylation
      of signal transducer and activator of transcription 6 (STAT6) was maximal. Only
      type I receptor, gammaC-dependent signaling induced efficient association of IRS
      2 with the p85 subunit of phosphoinositide 3-kinase or the adaptor protein growth
      factor receptor-bound protein 2. In addition, IL-4 signaling through type I IL
      4Rs induced more robust expression of a subset of genes associated with
      alternatively activated macrophages than did IL-13. Thus, IL-4 activates
      signaling pathways through type I IL-4Rs qualitatively differently from IL-13,
      which cooperate to induce optimal gene expression.

PMID- 19109242
TI  - Cefepime MIC breakpoint resettlement in gram-negative bacteria.

PMID- 19109243
TI  - Zinc deficiency mediates alcohol-induced alveolar epithelial and macrophage
      dysfunction in rats.
AB  - Chronic alcohol abuse impairs both alveolar epithelial and macrophage function,
      and renders individuals susceptible to acute lung injury, pneumonia, and other
      serious lung diseases. Zinc deficiency, which is known to impact both epithelial
      and immune cell functions, is also associated with alcohol abuse. In this study,
      chronic alcohol ingestion (6 wk) in rats altered expression of key zinc
      transporters and storage proteins in the small intestine and the lung, and
      decreased zinc levels in the alveolar compartment. Zinc supplementation of
      alveolar epithelial monolayers derived from alcohol-fed rats in vitro, or of the
      diets of alcohol-fed rats in vivo, restored alveolar epithelial barrier function,
      and these improvements were associated with salutary changes in tight junction
      protein expression and membrane localization. In parallel, dietary zinc
      supplementation increased intracellular zinc levels, GM-CSF receptor expression,
      and bacterial phagocytic capacity in the alveolar macrophages of alcohol-fed
      rats. Together, these studies implicate zinc deficiency as a novel mechanism
      mediating alcohol-induced alveolar epithelial and macrophage dysfunction.
      Importantly, these findings argue that dietary supplementation can overcome
      alcohol-induced zinc deficiency and restore alveolar epithelial and macrophage
      function, and therefore could be an effective treatment for the susceptible
      alcoholic lung phenotype.

PMID- 19109244
TI  - Anti-chemokine autoantibody:chemokine immune complexes activate endothelial cells
      via IgG receptors.
AB  - Our previous studies revealed that the presence in lung fluids of anti-IL-8
      autoantibody:IL-8 immune complexes is an important prognostic indicator for the
      development and outcome of acute lung injury (ALI)/acute respiratory distress
      syndrome (ARDS). Anti-IL-8:IL-8 complexes purified from lung edema fluids trigger
      chemotaxis of neutrophils, induce activation of these cells, and regulate their
      apoptosis, all via IgG receptor, FcgammaRIIa. Importantly, increased levels of
      FcgammaRIIa are present in lungs of patients with ARDS, where FcgammaRIIa is
      partially associated with anti-IL-8:IL-8 complexes. In the current study, we
      demonstrate the ability of anti-IL-8:IL-8 complexes to promote an inflammatory
      phenotype of human umbilical vein endothelial cells via interaction with
      FcgammaRIIa. Human umbilical vein endothelial cells cultured in the presence of
      the complexes become activated, as shown by increased phosphorylation of ERK,
      JNK, and Akt, and augmented nuclear translocation of NF-kappaB. Anti-IL-8:IL-8
      complexes also up-regulate expression of intracellular adhesion molecule (ICAM)-1
      on the cell surface. Furthermore, we detected increased levels of ICAM-1 on lung
      endothelial cells from mice in which lung injury was induced by generating immune
      complexes in alveolar spaces. On the other hand, ICAM-1 expression was unchanged
      in lungs of gamma chain-deficient mice, lacking receptors that interact with
      immune complexes. Moreover, in lung tissues from patients with ARDS, anti-IL-8:IL
      8 complexes were associated with endothelial cells that expressed higher levels
      of ICAM-1. Our current findings implicate that anti-chemokine
      autoantibody:chemokine immune complexes, such as IL-8:IL-8 complexes, may
      contribute to pathogenesis of lung inflammation by inducing activation of
      endothelial cells through engagement of IgG receptors.

PMID- 19109245
TI  - Improved Stratification of Autonomic Regulation for risk prediction in post
      infarction patients with preserved left ventricular function (ISAR-Risk).
AB  - AIMS: To investigate the combination of heart rate turbulence (HRT) and
      deceleration capacity (DC) as risk predictors in post-infarction patients with
      left ventricular ejection fraction (LVEF) > 30%. METHODS AND RESULTS: We enrolled
      2343 consecutive survivors of acute myocardial infarction (MI) (<76 years) in
      sinus rhythm. HRT and DC were obtained from 24 h Holter recordings. Patients with
      both abnormal HRT (slope < or = 2.5 ms/RR and onset > or = 0%) and abnormal DC (<
      or =4.5 ms) were considered suffering from severe autonomic failure (SAF) and
      prospectively classified as high risk. Primary and secondary endpoints were all
      cause, cardiac, and sudden cardiac mortality within the first 5 years of follow
      up. During follow-up, 181 patients died; 39 deaths occurred in 120 patients with
      LVEF < or = 30%, and 142 in 2223 patients with LVEF>30% (cumulative 5-year
      mortality rates of 37.9% and 7.8%, respectively). Among patients with LVEF > 30%,
      SAF identified another high-risk group of 117 patients with 37 deaths (cumulative
      5-year mortality rates of 38.6% and 6.1%, respectively). Merging both high-risk
      groups (i.e. LVEF < or = 30% and/or SAF) doubled the sensitivity of mortality
      prediction compared with LVEF < or = 30% alone (21.1% vs. 42.1%, P < 0.001) while
      preserving 5-year mortality rate (38.2%). CONCLUSION: In post-MI patients with
      LVEF>30%, SAF identifies a high-risk group equivalent in size and mortality risk
      to patients with LVEF < or = 30%.

PMID- 19109246
TI  - Spontaneous left main coronary artery dissection while skiing at altitude.

PMID- 19109248
TI  - Helicobacter pylori and lung function, asthma, atopy and allergic disease--a
      population-based cross-sectional study in adults.
AB  - BACKGROUND: Exposure to microbes may result in the polarization of the immune
      system and a decrease in the risk of asthma and associated allergic disease,
      whilst exposure to Helicobacter pylori has been hypothesized to increase the risk
      of obstructive airways disease. We tested the hypotheses that exposure to H.
      pylori reduces the risk of asthma and allergic disease and is associated with a
      decrease in lung function. METHODS: Data were collected on allergic disease
      symptoms, forced expiratory volume in 1 s (FEV1), forced vital capacity (FVC),
      bronchial reactivity, allergen skin sensitization, serum IgE and H. pylori
      serological status in 2437 randomly selected adults. RESULTS: Individuals with
      serological evidence of exposure to H. pylori had lower lung function, FEV1 being
      lower by 53 ml (95% CI 1-106) and FVC 83 ml (95% CI 20-145) lower in the cross
      sectional analysis. These differences ceased to be statistically significant
      after adjustment for height or socio-economic status. There was no association
      between H. pylori serological status and measures of asthma or atopy in the cross
      sectional analysis, and there was no significant association between H. pylori
      serological status and decline in FEV1 and FVC over 9 years. CONCLUSION: Although
      H. pylori exposure may be associated with lower cross-sectional FEV1 and FVC,
      this association was not independent of height or socio-economic status. There
      was no association between H. pylori exposure and either chronic obstructive
      pulmonary disease (COPD), measures of allergic disease or decline in lung
      function.

PMID- 19109247
TI  - Persistent pathogens linking socioeconomic position and cardiovascular disease in
      the US.
AB  - BACKGROUND: Numerous studies have documented a strong inverse association between
      cardiovascular disease and socioeconomic position (SEP). Several infections are
      associated with both cardiovascular disease and SEP; hence infection may form an
      important link between SEP and cardiovascular disease. This study examines
      whether seropositivity to cytomegalovirus (CMV), to herpes simplex virus type-1
      (HSV-1), and/or to both pathogens mediates the relationship between SEP and
      cardiovascular disease history in a nationally representative sample of the
      United States. METHODS: We conducted a cross-sectional study of subjects > or =45
      years of age, who were tested for seropositivity to CMV, HSV-1 or both pathogens
      and assessed for cardiovascular disease history in the National Health and
      Nutrition Examination Survey III. Cardiovascular disease history was defined as
      history of stroke, heart attack and/or congestive heart failure and SEP as
      education level. RESULTS: SEP was associated with CMV, HSV-1 and seropositivity
      to both pathogens. CMV seropositivity was associated with cardiovascular disease
      history even after adjusting for confounders as well as SEP. The odds of
      reporting a history of cardiovascular disease for those with less than a high
      school education compared with those with more than a high school education
      decreased by 7.7% after adjusting for CMV (Sobel mediation test for CMV, P =
      0.0006). In contrast, neither seropositivity to HSV-1 nor to both pathogens was
      associated with cardiovascular disease history after adjusting for SEP.
      CONCLUSIONS: Persistent pathogens such as CMV infection may explain a portion of
      the relationship between SEP and cardiovascular disease in the United States.
      Further studies examining additional pathogens and sociobiological mechanisms are
      warranted.

PMID- 19109249
TI  - Mechanism of Substrate and Inhibitor Binding of Rhodobacter capsulatus Xanthine
      Dehydrogenase.
AB  - Rhodobacter capsulatus xanthine dehydrogenase (XDH) is an (alphabeta)(2)
      heterotetrameric cytoplasmic enzyme that resembles eukaryotic xanthine
      oxidoreductases in respect to both amino acid sequence and structural fold. To
      obtain a detailed understanding of the mechanism of substrate and inhibitor
      binding at the active site, we solved crystal structures of R. capsulatus XDH in
      the presence of its substrates hypoxanthine, xanthine, and the inhibitor pterin-6
      aldehyde using either the inactive desulfo form of the enzyme or an active site
      mutant (E(B)232Q) to prevent substrate turnover. The hypoxanthine- and xanthine
      bound structures reveal the orientation of both substrates at the active site and
      show the importance of residue Glu(B)-232 for substrate positioning. The oxygen
      atom at the C-6 position of both substrates is oriented toward Arg(B)-310 in the
      active site. Thus the substrates bind in an orientation opposite to the one seen
      in the structure of the reduced enzyme with the inhibitor oxypurinol. The
      tightness of the substrates in the active site suggests that the intermediate
      products must exit the binding pocket to allow first the attack of the C-2,
      followed by oxidation of the C-8 atom to form the final product uric acid.
      Structural studies of pterin-6-aldehyde, a potent inhibitor of R. capsulatus XDH,
      contribute further to the understanding of the relative positioning of inhibitors
      and substrates in the binding pocket. Steady state kinetics reveal a competitive
      inhibition pattern with a K(i) of 103.57 +/- 18.96 nm for pterin-6-aldehyde.

PMID- 19109250
TI  - Structural Insights into KChIP4a Modulation of Kv4.3 Inactivation.
AB  - Dynamic inactivation in Kv4 A-type K(+) current plays a critical role in
      regulating neuronal excitability by shaping action potential waveform and
      duration. Multifunctional auxiliary KChIP1-4 subunits, which share a high
      homology in their C-terminal core regions, exhibit distinctive modulation of
      inactivation and surface expression of pore-forming Kv4 subunits. However, the
      structural differences that underlie the functional diversity of Kv channel
      interacting proteins (KChIPs) remain undetermined. Here we have described the
      crystal structure of KChIP4a at 3.0A resolution, which shows distinct N-terminal
      alpha-helices that differentiate it from other KChIPs. Biochemical experiments
      showed that competitive binding of the Kv4.3 N-terminal peptide to the
      hydrophobic groove of the core of KChIP4a causes the release of the KChIP4a N
      terminus that suppresses the inactivation of Kv4.3 channels. Electrophysiology
      experiments confirmed that the first N-terminal alpha-helix peptide (residues 1
      34) of KChIP4a, either by itself or fused to N-terminal truncated Kv4.3, can
      confer slow inactivation. We propose that N-terminal binding of Kv4.3 to the core
      of KChIP4a mobilizes the KChIP4a N terminus, which serves as the slow
      inactivation gate.

PMID- 19109252
TI  - Substrate Orientation and Catalysis at the Molybdenum Site in Xanthine Oxidase:
      CRYSTAL STRUCTURES IN COMPLEX WITH XANTHINE AND LUMAZINE.
AB  - Xanthine oxidoreductase is a ubiquitous cytoplasmic protein that catalyzes the
      final two steps in purine catabolism. We have previously investigated the
      catalytic mechanism of the enzyme by rapid reaction kinetics and x-ray
      crystallography using the poor substrate 2-hydroxy-6-methylpurine, focusing our
      attention on the orientation of substrate in the active site and the role of Arg
      880 in catalysis. Here we report additional crystal structures of as-isolated,
      functional xanthine oxidase in the course of reaction with the pterin substrate
      lumazine at 2.2 A resolution and of the nonfunctional desulfo form of the enzyme
      in complex with xanthine at 2.6 A resolution. In both cases the orientation of
      substrate is such that the pyrimidine subnucleus is oriented opposite to that
      seen with the slow substrate 2-hydroxy-6-methylpurine. The mechanistic
      implications as to how the ensemble of active site functional groups in the
      active site work to accelerate reaction rate are discussed.

PMID- 19109251
TI  - Distinct recruitment of Eps15 via Its coiled-coil domain is required for
      efficient down-regulation of the met receptor tyrosine kinase.
AB  - Down-regulation of receptor tyrosine kinases (RTK) through receptor
      internalization and degradation is critical for appropriate biological responses.
      The hepatocyte growth factor RTK (also known as Met) regulates epithelial
      remodeling, dispersal, and invasion and is deregulated in human cancers. Impaired
      down-regulation of the Met RTK leads to sustained signaling, cell transformation,
      and tumorigenesis, hence understanding mechanisms that regulate this process is
      crucial. Here we report that, following Met activation, the endocytic adaptor
      protein, Eps15, is recruited to the plasma membrane and becomes both tyrosine
      phosphorylated and ubiquitinated. Recruitment of Eps15 requires Met receptor
      kinase activity and involves two distinct Eps15 domains. Unlike previous reports
      for the EGF RTK, which requires the Eps15 ubiquitin interacting motif,
      recruitment of Eps15 to Met involves the coiled-coil domain of Eps15 and the
      signaling adaptor molecule, Grb2, which binds through a proline-rich motif in the
      third domain of Eps15. Expression of the coiled-coil domain is sufficient to
      displace the wild-type Eps15 protein complex from Met, resulting in loss of
      tyrosine phosphorylation of Eps15. Knockdown of Eps15 results in delayed Met
      degradation, which can be rescued by expression of Eps15 WT but not an Eps15
      mutant lacking the coiled-coil domain, identifying a role for this domain in
      Eps15-mediated Met down-modulation. This study demonstrates a new mechanism of
      recruitment for Eps15 downstream of the Met receptor, involving the coiled-coil
      domain of Eps15 as well as interaction of Eps15 with Grb2. This highlights
      distinct regulation of Eps15 recruitment and the diversity and adaptability of
      endocytic molecules in promoting RTK trafficking.

PMID- 19109253
TI  - p38 MAPK is an early determinant of promiscuous Smad2/3 signaling in the aortas
      of fibrillin-1 (Fbn1)-null mice.
AB  - Excessive transforming growth factor-beta (TGF-beta) signaling characterizes the
      progression of aortic aneurysm in mouse models of Marfan syndrome, a systemic
      disorder of the connective tissue that is caused by mutations in the gene
      encoding the extracellular matrix protein fibrillin-1. Fibrillin-1 mutations are
      believed to promote abnormal Smad2/3 signaling by impairing the sequestration of
      latent TGF-beta complexes into the extracellular matrix. Here we report that
      promiscuous Smad2/3 signaling is the cell-autonomous phenotype of primary
      cultures of vascular smooth muscle cells (VSMC) explanted from the thoracic
      aortas of Fbn1 mutant mice with either neonatal onset or progressively severe
      aortic aneurysm. This cellular phenotype was characterized in VSMC isolated from
      Fbn1-null (mgN/mgN) mice, which recapitulate the most severe form of Marfan
      syndrome. We found that loss of fibrillin-1 deposition promotes the production of
      intracellular reactive oxygen species and abnormal accumulation of phosphorylated
      TGF-beta-activated kinase 1 and p38 MAPK, in addition to increasing the levels of
      endogenous phospho-Smad2. We showed that improper Smad2/3 signaling in Fbn1-null
      VSMC is in part stimulated by phospho-p38 MAPK, which is in turn activated in
      response to signals other than those mediated by the kinase activity of the ALK5
      receptor. Consistent with these cell culture data, in vivo analyses documented
      that phospho-p38 MAPK accumulates earlier than phospho-Smad2 in the aortic wall
      of mgN/mgN mice and that systemic inhibition of phospho-p38 MAPK activity lowers
      the levels of phospho-Smad2 in this tissue. Collectively, these findings indicate
      that improper activation of p38 MAPK is a precursor of constitutive Smad2/3
      signaling in the aortic wall of a mouse model of neonatal lethal Marfan syndrome.

PMID- 19109254
TI  - SDF2L1, a component of the endoplasmic reticulum chaperone complex,
      differentially interacts with {alpha}-, {beta}-, and {theta}-defensin
      propeptides.
AB  - Mammalian defensins are cationic antimicrobial peptides that play a central role
      in host innate immunity and as regulators of acquired immunity. In animals, three
      structural defensin subfamilies, designated as alpha, beta, and , have been
      characterized, each possessing a distinctive tridisulfide motif. Mature alpha-
      and beta-defensins are produced by simple proteolytic processing of their
      prepropeptide precursors. In contrast, the macrocyclic -defensins are formed by
      the head-to-tail splicing of nonapeptides excised from a pair of prepropeptide
      precursors. Thus, elucidation of the -defensin biosynthetic pathway provides an
      opportunity to identify novel factors involved in this unique process. We
      incorporated the -defensin precursor, proRTD1a, into a bait construct for a yeast
      two-hybrid screen that identified rhesus macaque stromal cell-derived factor 2
      like protein 1 (SDF2L1), as an interactor. SDF2L1 is a component of the
      endoplasmic reticulum (ER) chaperone complex, which we found to also interact
      with alpha- and beta-defensins. However, analysis of the SDF2L1 domain
      requirements for binding of representative alpha-, beta-, and -defensins revealed
      that alpha- and beta-defensins bind SDF2L1 similarly, but differently from the
      interactions that mediate binding of SDF2L1 to pro--defensins. Thus, SDF2L1 is a
      factor involved in processing and/or sorting of all three defensin subfamilies.

PMID- 19109255
TI  - The nonplanar secretory IgA2 and near planar secretory IgA1 solution structures
      rationalize their different mucosal immune responses.
AB  - Secretory IgA (SIgA) is the most prevalent human antibody and is central to
      mucosal immunity. It exists as two subclasses, SIgA1 and SIgA2, where SIgA2 has a
      shorter hinge joining the Fab and Fc regions. Both forms of SIgA are
      predominantly dimeric and contain an additional protein called the secretory
      component (SC) that is attached during the secretory process and is believed to
      protect SIgA in harsh mucosal conditions. Here we locate the five SC domains
      relative to dimeric IgA2 within SIgA2 using constrained scattering modeling. The
      x-ray and sedimentation parameters showed that SIgA2 has an extended solution
      structure. The constrained modeling of SIgA2 was initiated using two IgA2
      monomers that were positioned according to our best fit solution structure for
      dimeric IgA1. SC was best located along the convex edge of the Fc-Fc region. The
      best fit models showed that SIgA2 is significantly nonplanar in its structure, in
      distinction to our previous near planar SIgA1 structure. Both the shorter IgA2
      hinges and the presence of SC appear to displace the four Fab regions out of the
      Fc plane in SIgA2. This may explain the noncovalent binding of SC in some SIgA2
      molecules. This nonplanar structure is predicted to result in specific immune
      properties for SIgA2 and SIgA1. It may explain differences observed between the
      SIgA1 and SIgA2 subclasses in terms of their interactions with antigens,
      susceptibility to proteases, effects on receptors, and distribution in different
      tissues. The different structures account for the prevalence of both forms in
      mucosal secretions.

PMID- 19109256
TI  - A new isoform of interleukin-3 receptor {alpha} with novel differentiation
      activity and high affinity binding mode.
AB  - Interleukin-3 (IL-3) promotes both self-renewal and differentiation of early
      multipotential progenitors and is involved in inducible hematopoiesis in response
      to infections. Here we report new insights into these processes with the
      identification of a new isoform (SP2) of IL-3 receptor alpha (IL-3Ralpha),
      present in mouse and human hematopoietic cells, which lacks domain 1 of the full
      length receptor (SP1). Binding assays with beta(IL-3) mutants showed that mouse
      SP2 uses a different high affinity binding mode to SP1, although both mouse and
      human SP2 and SP1 can stimulate IL-3-dependent growth. In IL-3-dependent
      differentiation models, human SP2 and SP1 gave differential effects on lineage
      commitment or self-renewal dependent on the cellular context, suggesting that
      different modes of ectodomain binding may modulate intracellular signaling. In a
      multipotential factor dependent cell-Paterson mix, the transcription factors
      C/EBPalpha and PU.1 and microRNAs miRNA-15a, -223, and -181a were up-regulated in
      cells undergoing SP2-supported differentiation compared with SP1-supported self
      renewal. Similarly in M1 cells, SP2 promoted differentiation compared with SP1
      and gave up-regulation of PU.1 and miRNA-155 and -223. These findings suggest
      that IL-3-promoted lineage commitment uses similar mechanisms to those of steady
      state hematopoiesis. Both the SP1 and SP2 isoforms activated the Jak2/STAT5, Akt,
      and Erk1/2 signaling pathways in M1 cells, although the activation was more
      prolonged for the SP2 isoform.

PMID- 19109257
TI  - Spontaneous mutational and standing genetic (co)variation at dinucleotide
      microsatellites in Caenorhabditis briggsae and Caenorhabditis elegans.
AB  - Understanding the evolutionary processes responsible for shaping genetic
      variation within and between species requires separating the effects of mutation
      and selection. Differences between the patterns of genetic variation observed in
      nature and when mutations are allowed to accumulate in the relative absence of
      selection can reveal biases imposed by selection. We characterize the genetic
      variation at dinucleotide microsatellite repeats in four sets of 250-generation
      mutation accumulation (MA) lines, two in the species Caenorhabditis briggsae and
      two in Caenorhabditis elegans, and compare the mutational variation with the
      standing variation in those species. We also compare the mutational properties of
      microsatellites with the cumulative effects of mutations on fitness in the same
      lines. Integrated over the whole genome, we infer that the mutation rate of C.
      briggsae is about twice that of C. elegans, consistent with the cumulative
      mutational effects on fitness. The mutational spectrum (ratio of insertions to
      deletions) differs between repeat types and, in some cases, between species. The
      per-locus mutation rate is significantly positively correlated with the standing
      genetic variation at the same locus in both species, providing justification for
      the common practice of using the standing genetic variance as a surrogate for the
      mutation rate.

PMID- 19109258
TI  - Invited review: assessing experimental designs for research conducted on
      commercial dairies.
AB  - Because of increasing constraints placed on conducting large studies at
      universities, more research is being conducted on commercial dairies, thereby
      raising some implications for experimental designs and data analysis. For
      example, experimental units are often specified to be pens of animals in on-farm
      studies, thereby requiring that at least 2 pens be used per treatment group in a
      single-dairy study. Even when treatments are compared within pens, the precision
      of inference on treatment differences is still primarily limited by the number of
      pens in the study, rather than the number of cows per treatment in each pen.
      Other challenges with on-farm studies include proper blocking and randomization
      of cows or pens to treatments. On the other hand, multiple farm studies are
      attractive, because they facilitate a broader scope of inference on treatment
      effects across a wider range of management or climatic conditions and genetic
      backgrounds compared with single-site university studies. Furthermore, studies
      based on multiple farms or multiple pens within a single large farm can
      facilitate greater power for treatment comparisons on binary reproduction or
      health responses than can be achieved at a smaller research herd. Because
      quantitative geneticists have been analyzing commercial dairy data for decades,
      they have developed useful data analysis techniques that should be harnessed to
      facilitate even greater statistical scope and power for on-farm studies.

PMID- 19109259
TI  - Invited review: reliability of genomic predictions for North American Holstein
      bulls.
AB  - Genetic progress will increase when breeders examine genotypes in addition to
      pedigrees and phenotypes. Genotypes for 38,416 markers and August 2003 genetic
      evaluations for 3,576 Holstein bulls born before 1999 were used to predict
      January 2008 daughter deviations for 1,759 bulls born from 1999 through 2002.
      Genotypes were generated using the Illumina BovineSNP50 BeadChip and DNA from
      semen contributed by US and Canadian artificial-insemination organizations to the
      Cooperative Dairy DNA Repository. Genomic predictions for 5 yield traits, 5
      fitness traits, 16 conformation traits, and net merit were computed using a
      linear model with an assumed normal distribution for marker effects and also
      using a nonlinear model with a heavier tailed prior distribution to account for
      major genes. The official parent average from 2003 and a 2003 parent average
      computed from only the subset of genotyped ancestors were combined with genomic
      predictions using a selection index. Combined predictions were more accurate than
      official parent averages for all 27 traits. The coefficients of determination
      (R(2)) were 0.05 to 0.38 greater with nonlinear genomic predictions included
      compared with those from parent average alone. Linear genomic predictions had
      R(2) values similar to those from nonlinear predictions but averaged just 0.01
      lower. The greatest benefits of genomic prediction were for fat percentage
      because of a known gene with a large effect. The R(2) values were converted to
      realized reliabilities by dividing by mean reliability of 2008 daughter
      deviations and then adding the difference between published and observed
      reliabilities of 2003 parent averages. When averaged across all traits, combined
      genomic predictions had realized reliabilities that were 23% greater than
      reliabilities of parent averages (50 vs. 27%), and gains in information were
      equivalent to 11 additional daughter records. Reliability increased more by
      doubling the number of bulls genotyped than the number of markers genotyped.
      Genomic prediction improves reliability by tracing the inheritance of genes even
      with small effects.

PMID- 19109260
TI  - Involvement of Acetobacter orientalis in the production of lactobionic acid in
      Caucasian yogurt ("Caspian Sea yogurt") in Japan.
AB  - Lactobionic acid was first found in a Caucasian fermented milk product popularly
      known as "Caspian Sea yogurt" in Japan. The presence of lactobionic acid in the
      fermented milk was indicated by the results of both high-performance anion
      exchange chromatographic analysis with pulsed amperometric detection and mass
      spectrometric analysis. Thereafter, the acid was purified from the yogurt and
      analyzed by nuclear magnetic resonance. A substantial amount of lactobionic acid
      was found to be accumulated in the upper layer of the yogurt, especially within
      10 mm from the surface. A total of 45 mg of lactobionic acid per 100 g of the
      upper yogurt layer was collected after 4 d of fermentation. The annual intake of
      lactobionic acid in individuals consuming 100 g of the yogurt every day would be
      0.5 to 1.0 g. A lactose-oxidizing bacterium was isolated from the fermented milk
      and was identified as Acetobacter orientalis. Washed A. orientalis cells oxidized
      monosaccharides such as d-glucose at considerable rates, although their
      activities for substrates such as lactose, maltose, and cellobiose were much
      lower. When A. orientalis cells were cultivated in cow's milk, they exhibited
      lactose-oxidizing activity, suggesting that this bacterium was the main organism
      involved in the production of lactobionic acid in the yogurt.

PMID- 19109261
TI  - Glycosylation and expanded utility of a modified whey protein ingredient via
      carbohydrate conjugation at low pH.
AB  - Whey protein, at one time considered a by-product of the cheese-making process,
      is now commonly used in foods for its thickening and emulsifying properties.
      Currently, approximately 30% of these proteinaceous resources remain under
      utilized. Previously, an acidified, thermally treated whey protein concentrate
      (mWPC) was developed to produce a cold-set thickening ingredient. Mass
      spectroscopy revealed an approximate 2.5-fold decrease in the lactosylation of
      beta-lactoglobulin in mWPC starting materials compared with commercial whey
      protein concentrates, manufactured at a higher pH. Potentially, this should
      increase the number of reactive sites that remain available for carbohydrate
      attachment. With this study, the formation of glycoprotein complexes was
      demonstrated between the mWPC ingredient and lactose, naturally occurring in mWPC
      powders, or between mWPC protein components with dextran (35 to 45 and 100 to 200
      kDa) materials at low pH. In fact, additional dry heating of mWPC powders showed
      a 3-fold increase in the amount of lactosylated beta-lactoglobulin. Evidence of
      Maillard reactivity was suggested using colorimetry, o-phthaldialdehyde assays,
      and sodium dodecyl sulfate PAGE followed by glycoprotein staining. Resultant
      glycoprotein dispersions exhibited altered functionality, in which case steady
      shear and small amplitude oscillatory rheology parameters were shown to be
      dependent on the specific reducing sugar present. Furthermore, the emulsion
      stability of mWPC-dextran fractions was 2 to 3 times greater than either mWPC or
      commercial WPC dispersions based on creaming index values. The water-holding
      capacity of all test samples decreased with additional heating steps; however,
      mWPC-dextran powders still retained nearly 6 times their weight of water.
      Scanning electron microscopy revealed that mWPC-dextran conjugates formed a
      porous network that differed significantly from the dense network observed with
      mWPC samples. This porosity likely affected both the rheological and water
      binding properties of mWPC-dextran complexes. Taken together, these results
      suggest that the functionality of mWPC ingredients can be enhanced by conjugation
      with carbohydrate materials at low pH, especially with regard to improving the
      emulsifying attributes.

PMID- 19109262
TI  - The accelerated ripening of cholesterol-reduced Cheddar cheese by crosslinked
      beta-cyclodextrin.
AB  - This study was carried out to investigate the influence of salt content on
      cholesterol-reduced Cheddar cheese obtained by a treatment with crosslinked beta
      cyclodextrin (beta-CD) and to find if the ripening process was accelerated in
      cholesterol-reduced cheese. The crosslinked beta-CD used was made by adipic acid.
      A primary study indicated that the chemical and rheological properties were not
      changed by the salt addition and the composition of Cheddar cheese treated with
      crosslinked beta-CD was similar to untreated Cheddar cheese. Approximately 91 to
      92% cholesterol reduction was observed in the cheeses that were treated using
      beta-CD. In a subsequent study, we found accelerated ripening by the crosslinked
      beta-CD based on the productions of short-chain free fatty acids and free amino
      acids. In rheological properties, elasticity, cohesiveness, and gumminess scores
      in the cholesterol-reduced Cheddar cheese were significantly greater at 5 wk
      ripening than those in the control at 4 mo ripening. At the early stage of
      ripening, most flavor properties such as rancidity, bitterness, and off-flavor in
      the cholesterol-reduced cheese were greater. With ripening, however, those scores
      changed to similar or lower scores than those in the control. The present study
      indicated that the crosslinked beta-CD treatment for cholesterol removal showed
      accelerated ripening effect on the properties of Cheddar cheese.

PMID- 19109263
TI  - Fat properties during homogenization, spray-drying, and storage affect the
      physical properties of dairy powders.
AB  - Changes in fat properties were studied before, during, and after the drying
      process (including during storage) to determine the consequences on powder
      physical properties. Several methods were combined to characterize changes in fat
      structure and thermal properties as well as the physical properties of powders.
      Emulsion droplet size and droplet aggregation depended on the homogenizing
      pressures and were also affected by spray atomization. Aggregation was usually
      greater after spray atomization, resulting in greater viscosities. These
      processes did not have the same consequences on the stability of fat in the
      powders. The quantification of free fat is a pertinent indicator of fat
      instability in the powders. Confocal laser scanning microscopy permitted the
      characterization of the structure of fat in situ in the powders. Powders from
      unhomogenized emulsions showed greater free fat content. Surface fat was always
      overrepresented, regardless of the composition and process parameters.
      Differential scanning calorimetry melting experiments showed that fat was
      partially crystallized in situ in the powders stored at 20 degrees C, and that it
      was unstable on a molecular scale. Thermal profiles were also related to the
      supramolecular structure of fat in the powder particle matrix. Powder physical
      properties depended on both composition and process conditions. The free fat
      content seemed to have a greater influence than surface fat on powder physical
      properties, except for wettability. This study clearly showed that an
      understanding of fat behavior is essential for controlling and improving the
      physical properties of fat-filled dairy powders and their overall quality.

PMID- 19109264
TI  - Proteolysis of yogurts made from ultra-high-pressure homogenized milk during cold
      storage.
AB  - Proteolysis was investigated in yogurts made from milk that was ultra-high
      pressure homogenized at 200 or 300 MPa and at 30 or 40 degrees C and compared
      with those produced from heat-treated milk containing 3% skim milk powder. To
      evaluate changes in the protein fraction, samples were analyzed at d 1, 7, 14,
      21, and 28 of storage for residual caseins, peptides, and total free amino acids.
      Results showed that yogurts from heat-treated milk and 300 MPa-treated milk
      presented similar levels of residual caseins, as well as similar profiles of
      soluble peptides and total free amino acids. On the contrary, greater amounts of
      hydrophobic peptides were detected in yogurts made from 200 MPa-treated milk at
      both 30 and 40 degrees C, especially at the end of storage. In all treatments
      studied, caseins were hydrolyzed and hydrophobic peptides were increased during
      storage, as reflected by the increase in soluble nitrogen at the end of the
      storage.

PMID- 19109265
TI  - Role of endogenous enzymes in proteolysis of sheep milk.
AB  - The aim of the present study was to determine the role of milk endogenous
      proteolytic enzymes in sheep milk cheesemaking ability during lactation. Plasmin,
      plasminogen, and plasminogen activator in ewe bulk milk were not significantly
      affected by stage of lactation, probably because of the good health of the ewe
      udders throughout lactation as indicated by somatic cell count, which never
      exceeded 600,000 cells/mL. Elastase content increased significantly during
      lactation, whereas cathepsin showed the greatest content in mid lactation. Early
      and mid lactation milk showed impaired renneting parameter compared with late
      lactation milk, probably because of greater alpha-casein degradation, brought
      about by cathepsin, and lesser fat and casein (CN) milk contents. Changes in
      macrophage and neutrophil levels in ewe bulk milk during lactation were also
      investigated. Macrophages minimally contributed to leukocyte cell count in milk
      and had the greatest levels at the beginning of lactation. An opposite trend was
      recorded for polymorphonuclear neutrophilic leucocytes (PMNL) that increased
      throughout lactation, showing the greatest value in late lactation. Urea-PAGE of
      sodium caseinate (NaCN) incubated with isolated and concentrated PMNL at 37
      degrees C after 48 h at pH 8 showed massive casein degradation that could be
      ascribed to proteases yielded by PMNL. The increase of PMNL percentage and
      elastase content in milk, despite the relatively low SCC, suggests that PMNL and
      elastase underwent a physiological increase associated to the remodeling of
      mammary gland in late lactation.

PMID- 19109266
TI  - Cheddar cheese classification based on flavor quality using a novel extraction
      method and Fourier transform infrared spectroscopy.
AB  - Analysis of Cheddar cheese flavor using trained sensory and grading panels is
      expensive and time consuming. A rapid and simple solvent extraction procedure in
      combination with Fourier transform infrared spectroscopy was developed for
      classifying Cheddar cheese based on flavor quality. Fifteen Cheddar cheese
      samples from 2 commercial production plants were ground into powders using liquid
      nitrogen. The water-soluble compounds from the cheese powder, without interfering
      compounds such as fat and protein, were extracted using water, chloroform, and
      ethanol. Aliquots (10 microL) of the extract were placed on a zinc selenide
      crystal, vacuum dried, and scanned in the mid-infrared region (4,000 to 700 cm(
      1)). The infrared spectra were analyzed by soft independent modeling of class
      analogy (SIMCA) for pattern recognition. Sensory flavor quality of these cheeses
      was determined by trained quality assurance personnel in the production
      facilities. The SIMCA models provided 3-dimensional classification plots in which
      all the 15 cheese samples formed well-separated clusters. The orientation of the
      clusters in 3-dimensional space correlated well with their cheese flavor
      characteristics (fermented, unclean, low flavor, sour, good Cheddar, and so on).
      The discrimination of the samples in the SIMCA plot was mainly due to organic
      acids, fatty acids and their esters, and amino acids (1,450 to 1,350 and 1,200 to
      990 cm(-1)), which are known to contribute significantly to cheese flavor. The
      total analysis time, including the sample preparation time, was less than 20 min
      per sample. This technique can be a rapid, inexpensive, and simple tool to the
      cheese industry for predicting the flavor quality of cheese.

PMID- 19109267
TI  - Technical note: characterizing individual milk fat globules with holographic
      video microscopy.
AB  - We used in-line holography to create images of individual milk fat globules in
      diluted samples of milk. Analyzing these images with the exact Lorenz-Mie light
      scattering theory then yields the droplets' radii with nanometer resolution and
      their refractive indexes to within one part in a thousand. This procedure rapidly
      and directly characterizes both the quantity and quality of fat in milk.

PMID- 19109268
TI  - Specific immune milk production of cows implanted with antigen-release devices.
AB  - A new antigen-release device (ARD) that can be implanted to enhance the titer of
      specific IgG and concentration of total IgG in milk of lactating cows was
      evaluated. An immunostimulating complex-based vaccine in the core of the ARD was
      made from the adjuvant Quil A and type XIII lipase from Pseudomonas spp. with a
      polylactide acid capsule that was used to control antigen release. Forty
      lactating Holstein dairy cows were divided into 2 groups (n = 20). All cows in
      the test group were implanted in the right iliac lymph node with 3 types of ARD
      at the same time, which were designed to release antigens on different days. The
      other group was used as a control with no implantation. The 3 ARD were designed
      to release the antigen on d 0, 14, and 28 after implantation. Specific IgG titers
      in whey and serum were measured by indirect ELISA, and total IgG concentrations
      were measured using sandwich ELISA. The results indicated that ARD implantation
      brought no negative effects on the health status, production performance of cows,
      and caused neither subclinical nor acute mastitis. The levels of specific IgG in
      serum (200,000 +/- 45,000 vs. 1,200 +/- 360) and whey (41,000 +/- 6,000 vs. 820
      +/- 210) increased in the cows implanted with ARD. Specific IgG in whey was
      increased after 9 d. The dynamics of specific IgG titer demonstrated a pattern
      with the release of the antigen from 3 types of ARD. The average ELISA titer of
      test group in whey was 41,000 +/- 6,000, which suggested high efficiency of
      immune milk production caused by the ARD implantation. For total IgG in milk,
      greater concentration in the test compared with the control cows occurred from 11
      to 20 d following implantation. The IgG mass was consistent with the dynamics of
      specific IgG titer and was higher from 15 to 30 d between test and control group
      (7.89 +/- 1.34 vs. 6.48 +/- 1.17 g). In conclusion, ARD implantation was
      effective in improving specific antibody concentration in serum and whey.
      Furthermore, the whey:serum ratio of specific IgG titer, the milk:serum ratio of
      total IgG concentration and total IgG mass in milk suggested that a transiently
      upregulated IgG transfer occurred after ARD implantation.

PMID- 19109269
TI  - Is the temperature-humidity index the best indicator of heat stress in lactating
      dairy cows in a subtropical environment?
AB  - Several temperature-humidity indexes (THI) have been used to estimate the degree
      of thermal stress experienced by dairy cows. The present objectives were to
      develop equations using meteorological variables that predicted rectal
      temperature of lactating cows in a subtropical environment and compare the
      goodness of fit of these equations to those using 8 different THI. Rectal
      temperature was measured between 1500 and 1700 h in 1,280 lactating Holstein cows
      in north central Florida between August and December. Meteorological data
      recorded in the barn where cows were located included dry bulb temperature
      (T(db)), relative humidity (RH), dew point temperature, and wind speed. Wet bulb
      temperature was calculated. In the first series of analyses, regression analysis
      was used to model rectal temperature using the meteorological variables as well
      as THI. The r(2) using T(db) (0.41) was slightly less than for models using all
      but one THI (r(2) between 0.42 and 0.43). The r(2) for equations using T(db)
      could be improved by adding RH (r(2) = 0.43) or RH and RH(2) (r(2) = 0.44) to the
      model. In the second analysis, regression analysis was performed using forward
      selection, backward elimination, and stepwise selection procedures with the
      meteorological variables. All models gave a similar goodness of fit (r(2) =
      0.44). An analysis of variance with rectal temperature as a class variable was
      performed to determine the least squares means of meteorological measurements
      associated with hyperthermia. A T(db) of 29.7 degrees C was associated with
      rectal temperature of 39 degrees C, and a T(db) of 31.4 degrees C was associated
      with rectal temperature of 39.5 degrees C. In conclusion, T(db) is nearly as good
      a predictor of rectal temperatures of lactating Holsteins in a subtropical
      environment as THI. Estimates of values of meteorological variables associated
      with specific rectal temperatures should prove valuable in relating environmental
      conditions to the magnitude of hyperthermia experienced by heat-stressed cows.

PMID- 19109270
TI  - Transcriptome profiling of Streptococcus uberis-induced mastitis reveals
      fundamental differences between immune gene expression in the mammary gland and
      in a primary cell culture model.
AB  - Streptococcus uberis is a prevalent causative organism of mastitis and resides
      naturally in the environment of the dairy cow making prevention of the disease
      difficult. A bovine cDNA microarray comprising approximately 22,000 expressed
      sequence tags was used to evaluate the transcriptional changes that occur in the
      mammary gland after the onset of clinical Strep. uberis mastitis. Five lactating
      Friesian heifers were intramammary infused in an uninfected quarter with
      approximately 1,000 to 1,500 cfu of a wild-type strain of Strep. uberis.
      Microarray results showed that Strep. uberis mastitis led to the differential
      expression of more than 2,200 genes by greater than 1.5-fold compared with
      noninfected control quarters. The most highly upregulated genes were associated
      with the immune response, programmed cell death, and oxidative stress.
      Quantitative real-time reverse transcription PCR analysis confirmed the increase
      in mRNA expression of immune-related genes complement component 3, clusterin, IL
      8, calgranulin C, IFN-gamma , IL-10, IL-1beta, IL-6, toll-like receptor-2, tumor
      necrosis factor-alpha, serum amyloid A3, lactoferrin, LPS-bonding protein, and
      oxidative stress-related genes metallothionein 1A and superoxide dimutase 2. In
      contrast, a decrease of mRNA levels was observed for the major milk protein
      genes. Bovine mammary epithelial cells in culture challenged with the same Strep.
      uberis strain used to induce clinical mastitis in the in vivo animal experiment
      did not cause a change in the mRNA levels of the immune-related genes. This
      suggests that the expression of immune-related genes by mammary epithelial cells
      may be initiated by host factors and not Strep. uberis. However, challenging
      epithelial cells with different Strep. uberis strains and Staphylococcus aureus
      resulted in an increase in the mRNA expression of a subset of the immune-related
      genes measured. In comparison, an Escherichia coli challenge caused an increase
      in the majority of immune-related genes measured. Results demonstrate the
      complexity of the bovine mammary gland immune response to an infecting pathogen
      and indicate that a coordinated response exists between the resident, recruited,
      and inducible immune factors.

PMID- 19109271
TI  - Effects of glucagon infusions on protein and amino acid composition of milk from
      dairy cows.
AB  - Changing the composition of milk proteins and AA affects the nutritional and
      physical properties of dairy products. Intravenous infusions of glucagon
      decreases milk protein production and concentration by promoting the use of
      gluconeogenic blood AA for hepatic glucose synthesis. Little is known about how
      the diversion of AA to gluconeogenesis affects the composition of milk proteins
      and AA. The objective was to quantify changes in composition of milk protein and
      AA in response to i.v. glucagon infusions. Three separate experiments were used:
      1) 8 Holstein cows were fed ad libitum and infused with glucagon at 10 mg/d for
      14 d, 2) 7 Holstein cows were feed restricted and infused with glucagon at 10
      mg/d for 14 d, and 3) 4 Brown Swiss cows were infused with glucagon at 5 and 10
      mg/d for 2 d each. Milk and milk component yields and milk protein and amino acid
      composition of samples, collected with blood samples at the first and last day of
      the glucagon infusion period, were compared with those collected 1 d before and
      after the glucagon infusion period. Glucagon infusions decreased milk protein
      production and concentration in each experiment by at least 0.2 +/- 0.05 kg/d and
      4 +/- 0.4 g/L, respectively. The decrease was accompanied by changes in milk
      protein composition, the most consistent being an increase in kappa-casein (1.68
      +/- 0.27%). Overall, glucagon infusions resulted in higher proportions of kappa
      casein and alpha(S2)-casein (1.34 +/- 0.51%) and smaller proportions of alpha(S1)
      casein (-3.83 +/- 1.75%) and alpha-lactalbumin (-0.91 +/- 0.32%). Glucagon had
      little impact on milk AA composition except an increase in glycine (0.26 +/-
      0.11%). The results suggest that milk protein synthesis is regulated by many
      factors including AA and glucose availability.

PMID- 19109272
TI  - Somatic cell count status across the dry period as a risk factor for the
      development of clinical mastitis in the subsequent lactation.
AB  - The objective of this study was to determine the risk of clinical mastitis in the
      first 120 d in lactation based on previous somatic cell count (SCC) history in a
      herd with a very low prevalence of contagious pathogens. A total of 218 cows from
      a university herd were enrolled at dry-off. Duplicate quarter milk samples were
      collected from all quarters at dry-off, postcalving (2 to 9 d in milk), and
      before treatment of all first cases of clinical mastitis that occurred during the
      first 120 d of the subsequent lactation. Quarter SCC statuses across the dry
      period were defined based on comparison of quarter SCC between the date of dry
      off and the postcalving sampling periods. The relationship between the
      probability of developing clinical mastitis in the first 120 d of lactation and
      SCC status across the dry period and other explanatory variables was assessed
      using logistic regression. In the first 120 d postcalving, 68 first cases of
      clinical mastitis occurred in 47 cows. Of quarters that experienced a
      microbiologically positive clinical case, the same microorganism was never
      isolated from milk samples obtained at dry-off or consistently isolated from milk
      samples collected at all sampling periods. Coagulase negative staphylococci were
      the most prevalent pathogens isolated from subclinical intramammary infection,
      whereas gram-negative pathogens were the most common pathogen associated with
      clinical cases. Quarters that had at least 1 case of mastitis during the previous
      lactation were 4.2 times more likely to have a first case of clinical mastitis in
      the current lactation than quarters that did not have clinical mastitis in the
      previous lactation [odds ratio (OR) = 4.2 (1.8, 10.0)]. Quarters of cows of
      greater than fourth parity were 4.2 times more likely to have a first case of
      clinical mastitis than quarters of cows of second parity [OR = 4.2 (1.4, 10.0)].
      Quarters with SCC > or =200,000 cells/mL at dry-off and postcalving were 2.7
      times more likely to experience a first case of mastitis than quarters with SCC
      <200,000 cells/mL at both periods [OR = 2.7 (0.97, 7.67)].

PMID- 19109273
TI  - Time to the occurrence of a decline in milk production in cows with various
      paratuberculosis antibody profiles.
AB  - Infection with Mycobacterium avium ssp. paratuberculosis (MAP) in dairy cattle
      often results in reduced milk production and premature culling. Some test
      positive animals can live for years without being affected by infection, whereas
      others are test negative when they die from the infection. Our objective was to
      describe the deviation in milk production of cows with various MAP antibody
      profiles compared with their repeatedly test-negative herdmates in the same
      parity. Data were obtained from herds participating in the Danish control program
      on paratuberculosis, for which 4 annual MAP antibody ELISA of individual cows
      were performed per herd per year. A total of 136,489 ELISA results from 38,998
      dairy cows in 64 herds were used along with 484,285 test-day records on energy
      corrected milk (ECM) yield. Cows were divided into 6 antibody groups based on
      their repeated milk ELISA results: A0) repeated ELISA negative; A1) ELISA
      negative, but only once; A2) ELISA negative on the last 3 tests, but with 1
      previous positive result; A3) ELISA negative on the last test, but with 1 or more
      previous positive results; A4) last sample was ELISA positive, but all previous
      were negative; and A5) at least the last 2 samples were ELISA positive. The
      expected test-day kilograms of ECM by herd and parity were estimated for cows in
      antibody group A0. Deviations from expected milk production were then assessed
      for cows in the other antibody groups relative to the time of the first test
      positive ELISA result (D 0). Cows in groups A2, A3, and A5 produced approximately
      0.5 kg of ECM/d more than cows in group A0 at 300 d before D 0. Cows in group A4
      had a decline in milk production from d 300 before D 0, with daily milk
      production reduced by 5 kg of ECM at 200 d after D 0. Milk production of cows in
      group A5 was reduced by 2.5 kg of ECM at 300 d after D 0 compared with 300 d
      before D 0, whereas cows in groups A2 and A3 produced 0.5 kg of ECM more than
      cows in group A0. The conclusions of the study were that 1) increasing the number
      ELISA tests increases the predictive value of ELISA for inference on milk
      production losses, 2) a combination of ELISA with assessment of observed milk
      production may be a valuable tool for decisions on culling, and 3) the declines
      in milk production attributable to MAP occurred over a long time period, and may
      not be realized by the herd manager without more advanced management tools such
      as the model proposed here.

PMID- 19109274
TI  - Short communication: effect of dry therapy using an intramammary infusion on bulk
      tank somatic cell count in sheep.
AB  - A total of 3,141 records of bulk tank milk somatic cell counts (BTSCC) and bulk
      tank milk total bacterial counts (BTTBC) were obtained over 24 mo from 25 dairy
      flocks of Assaf ewes belonging to the Consortium for Ovine Promotion in Castilla
      Leon, Spain, in which a complete dry therapy program was carried out in 10,313
      ewes using an antibiotic infusion containing 100 mg of penethamate hydriodide,
      280 mg of benethamine penicillin, and 100 mg of framycetin sulfate. The selection
      criteria for all flocks were BTSCC mean values > or =1,000 x 10(3) cells/mL and
      absence of dry therapy before the start of this experiment. Significant effects
      on log BTSCC were detected for treatment, milking system, flock within milking
      system, month within flock by treatment, the interactions treatment by milking
      system and flock by treatment within milking system, and log BTTBC. After dry
      therapy was implemented, log BTSCC decreased significantly in machine-milked
      flocks (5.95 +/- 0.007) compared with values before antibiotic treatment (6.13 +/
      0.008). The effect was observed at the beginning of the second lactation
      posttreatment (5.98 +/- 0.013). However, dry therapy was not effective in hand
      milked flocks, suggesting poor hygiene conditions. A significant relationship was
      found between BTSCC and BTTBC; therefore, programs for improving milk hygiene
      should be implemented for both BTSCC and BTTBC variables at the same time.

PMID- 19109275
TI  - Yeast culture supplementation prevented milk fat depression by a short-term
      dietary challenge with fermentable starch.
AB  - Effects of yeast culture on responses to a fermentable starch challenge were
      evaluated in an experiment with a crossover arrangement of treatments for yeast
      culture supplementation with 28-d periods and a fermentable starch challenge on
      the last 2 d of each 28-d period as a split plot within period. Eight ruminally
      cannulated, midlactation, multiparous Holstein cows (96 +/- 14 d in milk) were
      randomly assigned to treatment sequence. Treatments were yeast culture or control
      (mix of dry ground corn and soybean meal), top-dressed at 56 g per head per day
      throughout each period. Diets containing dry ground corn grain were fed from d 1
      through 26 of each period. On the last 2 d of each period, the dry ground corn
      was replaced by finely ground high-moisture corn grain on an equivalent dry
      matter basis to abruptly increase ruminal fermentability of dietary starch.
      Response variables were averaged for d 25 and 26 for the dry corn treatment and
      for d 27 and 28 for the high-moisture corn treatment each period. The fermentable
      starch challenge decreased dry matter intake by 1.9 kg/d and tended to increase
      milk yield compared with the dry corn diet. However, effects of the fermentable
      starch challenge on yield of milk fat varied for the yeast culture and control
      diets; yield of milk fat decreased from 1.42 to 1.30 kg/d for the control
      treatment but increased from 1.40 to 1.47 kg/d for the yeast culture treatment.
      Milk fat concentration tended to decrease from 3.34 to 3.03% during the dietary
      challenge compared with the base diet for the control treatment but was not
      affected (mean = 3.32%) by the dietary challenge for the yeast culture treatment.
      An interaction of treatments was also detected for fat-corrected milk, which
      increased from 41.0 to 43.0 kg/d for the yeast culture treatment but decreased
      from 41.6 to 39.8 kg/d for the control diet with the fermentable starch
      challenge. Frequency of ruminating bouts was decreased by yeast culture compared
      with control (12.8 vs. 15.7 bouts/d) but not the fermentable starch challenge. No
      treatment interactions were observed for any measure of ruminal pH, total or
      individual volatile fatty acid concentration in ruminal fluid, acetate:propionate
      ratio, or individual fatty acid isomers in milk fat. Yeast culture
      supplementation may help prevent depression in milk fat during transition to a
      diet with highly fermentable starch, but the mechanism responsible remains to be
      elucidated.

PMID- 19109276
TI  - Effect of restricted access time to pasture on dairy cow milk production, grazing
      behavior, and dry matter intake.
AB  - The objective of this experiment was to investigate the effect of restricting
      pasture access time on milk production and composition, body weight and body
      condition score change, dry matter intake, and grazing behavior of autumn calving
      dairy cows in midlactation. Fifty-two (19 primiparous and 33 multiparous)
      Holstein-Friesian dairy cows (mean calving date, August 17 +/- 91.2 d) were
      randomly assigned to a 4-treatment (n = 13) randomized block design grazing
      study. The 4 grazing treatments were: (i) full-time access to pasture (22H;
      control), (ii) 9-h access to pasture (9H), (iii) two 4.5-h periods of access to
      pasture after both milkings (2 x 4.5H), and (iv) two 3-h periods of access to
      pasture after both milkings (2 x 3H). Experimental treatments were imposed from
      March 7 to April 6, 2007 (31 d). The pregrazing herbage mass of swards offered to
      all treatments was 1,268 kg of dry matter/ha, and sward organic matter
      digestibility was 86.4%, indicating high-quality swards conducive to high dry
      matter intake. Swards where animals had 22H and 2 x 4.5H access to pasture had
      the lowest postgrazing sward heights (3.5 cm), reflecting the greatest levels of
      sward utilization. After the experimental period, there were no differences in
      milk production; however, the 2 x 3H animals tended to have lower milk protein
      concentration (-0.17%) compared with 22H animals. Furthermore, dry matter intake
      of the 9H animals was lower than 22H animals. Although restricting access time to
      pasture decreased grazing time, animals compensated by increasing their
      intake/minute and intake/bite. Restricting pasture access time resulted in much
      greater grazing efficiency, because the 9H, 2 x 4.5H, and 2 x 3H treatments spent
      a greater proportion of their time at pasture grazing (81, 81, and 96%,
      respectively) than 22H animals (42%). Results of this study indicate that
      allocating animals restricted access to pasture does not significantly affect
      milk production. This study also found that the total access time should be
      greater than 6 h and that perhaps needs to be divided into 2 periods.

PMID- 19109277
TI  - Evidence for the inhibition of the terminal step of ruminal alpha-linolenic acid
      biohydrogenation by condensed tannins.
AB  - Effects of condensed tannins (CT), either via extract or plant-bound, and saponin
      extract on ruminal biohydrogenation of alpha-linolenic acid (ALA) were
      investigated in vitro. Grass-clover hay served as basal diet (control). The
      control hay was supplemented with extracts contributing either CT from Acacia
      mearnsii [7.9% of dietary dry matter (DM)] or saponins from Yucca schidigera
      (1.1% of DM). The fourth treatment consisted of dried sainfoin (Onobrychis
      viciifolia), a CT-containing forage legume, in an amount also providing 7.9% CT
      in dietary DM. All diets were supplemented with linseed oil at a level
      contributing 60% of total dietary ALA in all treatments. Diets were incubated for
      10 d (n = 4) in the rumen simulation technique system, using the last 5 d for
      statistical evaluation. Fatty acids were analyzed in feed, feed residues,
      incubation fluid, and its effluent. Data were subjected to ANOVA considering diet
      and experimental run as main effects. Both CT treatments reduced ruminal fiber
      and crude protein degradation, and lowered incubation fluid ammonia
      concentration. Only the CT extract suppressed methane formation and shifted
      microbial populations toward bacteria at cost of protozoa. The saponin extract
      remained without clear effects on fermentation characteristics except for
      increased protozoal counts. The extent of ALA biohydrogenation was 20% less with
      the CT plant, but this probably resulted from reduced organic matter
      degradability rather than from an inhibition of biohydrogenation. After
      incubation analysis of incubation fluid effluent and feed residues showed a
      considerable proportion of the 3 biohydrogenation intermediates, cis-9, trans-11,
      cis-15 C18:3, trans-11, cis-15 C18:2, and trans-11 C18:1, which did not occur in
      the initial feeds. Only the CT-extract diet led to a different profile in the
      effluent compared with the control diet with trans-11 C18:1 being considerably
      increased at cost of C18:0. This could have been achieved by suppressing protozoa
      and enhancing the bacterial population, thus removing potential microbes involved
      in biohydrogenation and increasing competition between bacteria involved in
      biohydrogenation and others. The elevation of trans-11 C18:1 as the precursor of
      cis-9, trans-11 conjugated linoleic acid formed in body tissue and mammary gland
      is probably favorable from a human health point of view.

PMID- 19109278
TI  - Digestion during continuous culture fermentation when replacing perennial
      ryegrass with barley and steam-flaked corn.
AB  - The objective of this study was to quantify the optimal inclusion rate of grain
      required to maximize nutrient digestion of a diet based on highly digestible
      pasture. It was hypothesized that maximum digestion would occur at a rate of
      grain inclusion that resulted in a culture pH of 6.0, reflecting the pH below
      which fiber digestion would be expected to be compromised. Four dual-flow
      continuous culture fermenters were used to establish the effects on digestion of
      replacing freeze-dried, highly digestible ryegrass with 0, 15, 30, and 45% of dry
      matter as 60% barley, 35% steam-flaked corn, and 5% molasses mix. The respective
      composite diets were fed twice daily to mimic intake patterns observed in dairy
      cows offered supplements during milking and offered half their daily allowance of
      pasture after each milking. Digesta samples were collected during the last 3 d of
      each of four 9-d experimental periods. Average daily culture pH decreased
      linearly as proportion of cereal grain in the diet increased, with average daily
      pH ranging from 6.29 to 5.74. Concentrations of neutral detergent fiber and total
      fatty acids decreased linearly with increasing proportion of cereal grain in the
      diet. Digestion of organic matter (OM) was maximized at an interpolated value of
      24% grain inclusion and culture pH of 6.0, but the difference in the OM
      digestibility over the range of grain treatments from 0 to 45% was small (3
      percentage units) despite pH changes over a range of 6.3 to 5.7. The relatively
      small change in OM digestibility was explained by reduced fiber and crude protein
      digestibilities being balanced by an increased digestion of nonstructural
      carbohydrate. Although different relationships between ruminal pH and
      digestibility appear to exist when cows are fed pasture alone compared with a
      total mixed ration, when starch supplements are included in pasture diets, the
      relationships associated with feeding a total mixed ration may then be more
      likely to apply.

PMID- 19109279
TI  - Effects of lipid supplementation on the yield and composition of milk from cows
      with different beta-lactoglobulin phenotypes.
AB  - Responses to lipid supplementation differ between dairy breeds and genetic lines
      suggesting nutrition by genotype interactions. beta-Lactoglobulin phenotype is
      associated with changes in yield and composition of milk. The response of cows
      with different beta-lactoglobulin phenotypes to lipid supplementation has not
      been examined. Furthermore, we examined whether lipid supplementation alters milk
      protein composition. By using a randomized block design, we fed Holstein cows for
      3 wk either a control diet containing 2.8% crude fat (n = 19) or an experimental
      diet that was supplemented with 4.2% tallow (n = 20). Before randomization, all
      cows were fed the supplemental tallow diet for at least 2 wk. Dry matter intake,
      body weight, milk yield, and milk composition were measured in the last week
      before and during the experimental period. Feeding supplemental tallow increased
      dry matter intake and yields of milk and milk components, including casein
      content, without decreasing milk component content or altering milk protein
      composition. On the low-fat control diet, cows with the beta-lactoglobulin allele
      B had a greater milk and milk component yield than cows with the A allele,
      whereas no differences by beta-lactoglobulin phenotype were observed in cows on
      the tallow supplement diet. Our results suggest that cows that differ in beta
      lactoglobulin phenotype respond differently to a low-fat diet and that feeding
      cows 4.2% of additional tallow increases milk yield without affecting milk
      component content and milk protein composition.

PMID- 19109280
TI  - Nutritional and management strategies on nitrogen and phosphorus use efficiency
      of lactating dairy cattle on commercial farms: an environmental perspective.
AB  - Dairy farm activities contribute to environmental pollution through the surplus N
      and P that they produce. Optimization of animal feeding and management has been
      described as a key strategy for decreasing N and P excretion in manure. Sixty
      four commercial dairy farms were studied to assess the efficiency of N and P use
      in lactating herds and to identify dietary and management factors that may
      contribute to improving the efficiency of nutrient use for milk production, and
      decrease N and P excretion. The average ration was formulated to 50:50
      forage:concentrate ratio with grass silage and corn silage as the main forage
      sources. Mean N and P intakes were 562 g/d [16.4% crude protein (CP)] and 84.8
      g/d (0.40% P), respectively. Milk yield averaged 29.7 kg/d and contributed to
      25.8% (standard deviation +/- 2.9) of N utilization efficiency (NUE) and 31.9%
      (standard deviation +/- 4.5) of P utilization efficiency (PUE). Dietary N
      manipulation through fitting the intake of CP to animal requirements showed a
      better response in terms of decreasing N excretion (R(2) = 0.70) than that
      estimated for P nutrition and excretion (R(2) = 0.30). Improvement in NUE helped
      increase PUE, despite the widespread use of feedstuffs with a high P content.
      Management strategies for lactating herds, such as the use of different feeding
      groups, periodical ration reformulation, and selection of feeding system did not
      show any consistent response in terms of improved NUE and PUE. The optimization
      of NUE and PUE contributed to decreasing the N and P excretion per unit of milk
      produced, and therefore, reductions in N and P excretion of between 17 and 35%,
      respectively, were estimated. Nevertheless, nutritional and herd management
      strategies were limited when N and P excretion were considered in relation to the
      whole lactating herd and farmland availability. Dietary CP manipulation was
      estimated to decrease herd N excretion by 11% per hectare, whereas dietary P
      manipulation would be decreased by no more than 17%. We conclude that the correct
      match between the ingested and required N and P, together with an increase in
      milk productivity, may be feasible strategies for decreasing N and P excretion by
      lactating herds on commercial farms.

PMID- 19109281
TI  - Insulin resistance in divergent strains of Holstein-Friesian dairy cows offered
      fresh pasture and increasing amounts of concentrate in early lactation.
AB  - The objective of this study was to determine whether the physiological response
      to an intravenous glucose challenge would be affected by genetic strain or
      concentrate supplementation in grazing Holstein-Friesian cows in early lactation.
      North American (NA; n = 30) or New Zealand (NZ; n = 30) cows were randomly
      allocated to 1 of 3 feeding treatments. All cows were offered a generous pasture
      allowance, and 4 of the 6 groups received either 3 or 6 kg of dry matter (DM)/cow
      per day of concentrates. During wk 5 of lactation, all cows underwent an
      intravenous glucose challenge. Cows of NA origin produced more milk than NZ cows,
      but there was no significant strain effect on milk fat or protein yield. Milk
      yield and the yield of individual components increased with increasing level of
      concentrate eaten, but there were no significant strain x diet interactions.
      During wk 1 to 6, mean body weight and body condition score decreased in all
      treatments. Average body weight was greater in NA cows, but body condition score
      was greater for NZ cows. There was no strain or diet effect on the length of the
      postpartum anovulatory interval, with cows ovulating before 40 d postpartum on
      average. Glucose fractional turnover rate was greater in NZ cows compared with
      those of NA origin and in all cows receiving 6 kg of DM concentrates, indicating
      a less severe insulin resistance in those treatments. Consistent with this, the
      time taken to dispose of half the peak glucose concentration was less when 6 kg
      of DM concentrate was fed, and tended to be less in NZ than in NA cows. There was
      no effect of genetic strain on glucose area under the curve (AUC) at 60 or 120
      min, but AUC at both time points was less in cows receiving 6 kg of DM
      concentrates per day. Neither genetic strain nor nutrition affected basal or peak
      insulin concentrations, insulin increment, or insulin AUC, and there were no
      strain x diet interactions for any of the glucose challenge response variables
      measured. In conclusion, differences in milk production between NA and NZ cows in
      early lactation can, at least in part, be explained by the greater degree of
      insulin resistance in the NA cows, and this insulin resistance can be overcome by
      supplementing grazing cows with 6 kg of DM concentrates.

PMID- 19109282
TI  - Dietary calcium has little effect on mineral balance and bone mineral metabolism
      through twenty weeks of lactation in Holstein cows.
AB  - Calcium and P balance and mobilization from bone were evaluated through 20 wk of
      lactation to determine the timing and extent of net resorption of bone mineral
      and mineral balance in lactating dairy cows. Eighteen Holstein cows were blocked
      by parity and calving date and randomly assigned to 1 of 3 dietary treatments:
      high (1.03%, HI), medium (0.78%, MED), or low (0.52%, LOW) dietary Ca. Dietary P
      was 0.34% in all diets. Cows consumed treatment diets from calving to 140 DIM.
      Total collection of milk, urine, and feces was conducted 2 wk before expected
      calving and in wk 2, 5, 8, 11, and 20 of lactation. Blood samples were collected
      at 14 and 10 d before expected calving and 0, 1, 3, 5, 10, 14, 21, 28, 35, 56,
      70, 84, 98, and 140 d after calving. Blood samples were analyzed for Ca, P, and
      parathyroid hormone concentration. Serum concentrations of osteocalcin (OC), a
      marker of bone formation, and deoxypyridinoline (DPD), a marker of bone
      resorption, were measured to assess bone mobilization. Rib bone biopsies were
      conducted within 10 d postcalving and during wk 11 and 20 of lactation. Dietary
      Ca concentration affected Ca balance, with cows consuming the HI Ca diet in
      positive Ca balance for all weeks with the exception of wk 11. Interestingly, all
      cows across all treatments had a negative Ca balance at wk 11, possibly the
      result of timed estrous synchronization that occurred during wk 11. At wk 20, Ca
      balances were 61.2, 29.9, and 8.1 g/d for the HI, MED, and LOW diets,
      respectively. Phosphorus balances across all treatments and weeks were negative.
      Bone Ca content on a fat-free ash weight basis was least in cows consuming the
      MED diet, but bone P was not different. Serum Ca and P were not affected by
      treatment. Dietary Ca concentration did not affect P balance in the weeks
      examined, but there was a clear effect of parity on balance, markers of bone
      metabolism, and bone P. Primiparous cows had greater serum OC and DPD
      concentrations than multiparous cows. Regardless of dietary treatment, serum OC
      concentration peaked around d 35 of lactation. Simultaneously, DPD concentration
      began to decrease, which may indicate a switch from net bone resorption to
      formation after d 35. However, this was not reflected in balance measures. This
      information may help refine dietary mineral recommendations for lactating dairy
      cows and suggests that dietary P requirements are independent of dietary Ca.

PMID- 19109283
TI  - Timothy hays differing in dietary cation-anion difference affect the capability
      of dairy cows to maintain their calcium homeostasis.
AB  - Forages low in dietary cation-anion difference (DCAD) can be used to decrease the
      DCAD in prepartum diet but the extent to which DCAD needs to be reduced is of
      recent interest. The objective of this study was to evaluate the effectiveness of
      timothy hays differing in DCAD at maintaining Ca homeostasis. Six nonlactating
      and nonpregnant multiparous Holstein cows were fed diets containing timothy
      (Phleum pratense L.) hay with DCAD values of 4.1 +/- 3.6 (LOW), 14.1 +/- 3.0
      (MED), or 25.1 +/- 2.5 (HIGH) mEq per 100 g of DM in a duplicated 3 x 3 Latin
      square design with 14-d experimental periods. The LOW and MED hays were produced
      by fertilizing established timothy fields at a rate of 224 kg CaCl(2) per ha, and
      HIGH hay was obtained from the same field where LOW hay was produced, but from a
      section not fertilized with CaCl(2). Experimental diets, containing LOW, MED, or
      HIGH timothy hay at 71% of dietary DM, had DCAD values of 0.7, 7.3, and 14.4 mEq
      per 100 g of DM, respectively. Animals were fed at 6% of metabolic body weight,
      which provided 108% of their daily energy requirement. For each period, after a
      12 d diet adaptation, cows were subjected to an EDTA challenge (3 cows each on d
      13 and 14). Infusion of EDTA solution into the jugular vein decreases the
      concentration of blood ionized Ca, and the EDTA challenge protocol determined the
      resistance time and recovery time: the time required for the blood ionized Ca
      concentration to decrease to 60%, and the time required to recover to 90% of the
      prechallenge concentrations, respectively. Urine pH was lower when cows were fed
      LOW compared with HIGH diet (6.88 vs. 7.83), but urine pH when cows were fed MED
      diet (7.15) did not differ from that when cows received the LOW or HIGH diet.
      However, immediately before the EDTA challenge, blood pH was lower when cows were
      fed LOW or MED compared with HIGH diet (7.44 vs. 7.47). Although the resistance
      time was not affected by treatments, the recovery time was shorter when cows were
      fed the LOW compared with MED or HIGH diet (185 vs. 248 and 263 min,
      respectively). Blood pH decreased when cows were fed the LOW or MED diet, but the
      capability to maintain Ca homeostasis was enhanced only when cows received the
      LOW diet, in which the DCAD value was decreased to 1 mEq per 100 g of DM.

PMID- 19109284
TI  - Effects of strain of Holstein-Friesian and concentrate supplementation on the
      fatty acid composition of milk fat of dairy cows grazing pasture in early
      lactation.
AB  - The effect of a grain-based concentrate supplement on fatty acid (FA) intake and
      concentration of milk FA in early lactation was investigated in grazing dairy
      cows that differed in their country of origin and in their estimated breeding
      value for milk yield. It was hypothesized that Holstein-Friesian cows of North
      American (NA) origin would produce milk lower in milk fat than those of New
      Zealand (NZ) origin, and that the difference would be associated with lower de
      novo synthesis of FA. In comparison, increasing the intake of concentrates should
      have the same effect on the FA composition of the milk from both strains. Fifty
      four cows were randomly assigned in a factorial arrangement to treatments
      including 3 amounts of concentrate daily [0, 3, and 6 kg of dry matter (DM)/cow]
      and the 2 strains. The barley/steam-flaked corn concentrate contained 3.5% DM FA,
      with C18:2, C16:0, and C18:1 contributing 48, 18, and 16% of the total FA. The
      pasture consumed by the cows contained 4.6% DM FA with C18:3, C16:0, and C18:1
      contributing 51, 10, and 10% of the FA, respectively. Pasture DM intake decreased
      linearly with supplementation, but total DM intake was not different between
      concentrate or strain treatments, averaging 16.2 kg of DM/cow, with cows
      consuming 720 g of total FA/d. Cows of the NA strain had lesser concentrations of
      milk fat compared with NZ cows (3.58 vs. 3.95%). Milk fat from the NA cows had
      lesser concentrations of C6:0, C8:0, C10:0, C12:0, C14:0, and C16:0, and greater
      concentrations of cis-9 C18:1, C18:2, and cis-9, trans-11 C18:2, than NZ cows.
      These changes indicated that in milk from NA cows had a lesser concentration of
      de novo synthesized FA and a greater concentration of FA of dietary origin. Milk
      fat concentration was not affected by concentrate supplementation. Increasing
      concentrate intake resulted in linear increases in the concentrations of C10:0,
      C12:0, C14:0, and C18:2 FA in milk fat, and a linear decrease in the
      concentration of C4:0 FA. The combination of NA cows fed pasture alone resulted
      in a FA composition of milk that was potentially most beneficial from a human
      health perspective; however, this would need to be balanced against other aspects
      of the productivity of these animals.

PMID- 19109285
TI  - Rumen ciliated protozoa decrease generation time and adjust 18S ribosomal DNA
      copies to adapt to decreased transfer interval, starvation, and monensin.
AB  - Defaunation studies have documented decreased ammonia concentrations associated
      with reduced microbial protein recycling and wastage of dietary protein, whereas
      many methods to suppress protozoa can reduce feed intake or depress ruminal
      organic matter or fiber digestibility. Therefore, more research is needed to
      optimize dietary conditions that improve protozoal growth and ruminal outflow
      relative to autolysis and recycling. Response in growth rate to ruminal outflow
      was simulated by abrupt changes in transfer interval of batch cultures, and
      substrate availability was evaluated by feeding without or with abrupt addition
      of monensin, which was postulated to inhibit digestive vacuole function. In
      experiment 1, Entodinium caudatum, a mix of Entodinium species, Epidinium
      caudatum, or Ophryoscolex caudatus cultures rapidly adjusted their generation
      times to approach respective changes in transfer interval from 3 to 2 or 1 d
      (cultures were always fed at 24-h intervals). Monensin (0.25 microM) consistently
      delayed this response. To evaluate a metabolic upshift associated with feeding or
      a downshift associated with substrate depletion, experiment 2 used real-time PCR
      to quantify protozoal 18S rRNA gene (rDNA) copies that were expressed relative to
      cell numbers or to the cellular constituents N and nucleic acids after feeding
      without or with monensin (0.5 microM). The 18S rDNA copies per milligram of
      nucleic acids were least for Ophryoscolex compared with the other cultures. When
      averaged over cultures (no culture x treatment interaction), 18S rDNA copies per
      unit of nucleic acids decreased at 16 h when cultures were starved but increased
      with feeding unless monensin uncoupled availability of consumed substrate. Rumen
      protozoal growth increased in response to decreased transfer interval in
      experiment 1. Substrate availability appeared to initiate metabolic responses
      preparing for cell growth, explaining how cultures could rapidly adjust to
      decreasing transfer interval in experiment 2. Because feeding was not coupled
      with transfer in experiment 2, however, a metabolic control probably arrested
      cell division to prevent overgrowth relative to substrate availability.

PMID- 19109286
TI  - Interaction of molasses and monensin in alfalfa hay- or corn silage-based diets
      on rumen fermentation, total tract digestibility, and milk production by Holstein
      cows.
AB  - Sugar supplementation can stimulate rumen microbial growth and possibly fiber
      digestibility; however, excess ruminal carbohydrate availability relative to
      rumen-degradable protein (RDP) can promote energy spilling by microbes, decrease
      rumen pH, or depress fiber digestibility. Both RDP supply and rumen pH might be
      altered by forage source and monensin. Therefore, the objective of this study was
      to evaluate interactions of a sugar source (molasses) with monensin and 2 forage
      sources on rumen fermentation, total tract digestibility, and production and
      fatty acid composition of milk. Seven ruminally cannulated lactating Holstein
      cows were used in a 5 x 7 incomplete Latin square design with five 28-d periods.
      Four corn silage diets consisted of 1) control (C), 2) 2.6% molasses (M), 3) 2.6%
      molasses plus 0.45% urea (MU), or 4) 2.6% molasses plus 0.45% urea plus monensin
      sodium (Rumensin, at the intermediate dosage from the label, 16 g/909 kg of dry
      matter; MUR). Three chopped alfalfa hay diets consisted of 1) control (C), 2)
      2.6% molasses (M), or 3) 2.6% molasses plus Rumensin (MR). Urea was added to corn
      silage diets to provide RDP comparable to alfalfa hay diets with no urea. Corn
      silage C and M diets were balanced to have 16.2% crude protein; and the remaining
      diets, 17.2% crude protein. Dry matter intake was not affected by treatment, but
      there was a trend for lower milk production in alfalfa hay diets compared with
      corn silage diets. Despite increased total volatile fatty acid and acetate
      concentrations in the rumen, total tract organic matter digestibility was lower
      for alfalfa hay-fed cows. Rumensin did not affect volatile fatty acid
      concentrations but decreased milk fat from 3.22 to 2.72% in corn silage diets but
      less in alfalfa hay diets. Medium-chain milk fatty acids (% of total fat) were
      lower for alfalfa hay compared with corn silage diets, and short-chain milk fatty
      acids tended to decrease when Rumensin was added. In whole rumen contents,
      concentrations of trans-10, cis-12 C(18:2) were increased when cows were fed corn
      silage diets. Rumensin had no effect on conjugated linoleic acid isomers in
      either milk or rumen contents but tended to increase the concentration of trans
      10 C(18:1) in rumen samples. Molasses with urea increased ruminal NH(3)-N and
      milk urea N when cows were fed corn silage diets (6.8 vs. 11.3 and 7.6 vs. 12.0
      mg/dL for M vs. MU, respectively). Based on ruminal fermentation characteristics
      and fatty acid isomers in milk, molasses did not appear to promote ruminal
      acidosis or milk fat depression. However, combinations of Rumensin with corn
      silage-based diets already containing molasses and with a relatively high
      nonfiber carbohydrate:forage neutral detergent fiber ratio influenced
      biohydrogenation characteristics that are indicators of increased risk for milk
      fat depression.

PMID- 19109287
TI  - Evaluation of the effects of oral colostrum supplementation during the first
      fourteen days on the health and performance of preweaned calves.
AB  - Increasing concerns about antimicrobial resistance have led to the development
      and implementation of alternatives to antimicrobial use in animal production. The
      objective of this clinical trial was to determine the effect of colostrum
      supplementation of the milk replacer ration on morbidity, mortality, feed intake,
      and weight gain of preweaned calves. Ninety 1-d-old calves on each of 3
      commercial calf ranches were randomly allocated to 1 of 3 groups. Treatment-group
      calves received 10 g of supplemental immunoglobulin G (IgG) in the form of 70 g
      of colostrum powder in the milk replacer twice daily for 14 d. The placebo-group
      calves received a nutritionally equivalent supplement lacking IgG in the milk
      replacer twice daily for 14 d. Control calves received milk replacer without
      supplements twice daily. Calves were housed in individual hutches and were
      weighed on d 1, 28, and 60. Serum was collected on d 2 for serum IgG
      determination. Daily health evaluations for the first 28 d of life were performed
      by study personnel blinded to treatment group assignment. Observed illness was
      treated based on health assessment, rectal temperature, and specific calf ranch
      protocols. Feed consumption (milk and grain) was recorded. Calves receiving
      supplemental colostrum had less diarrhea and received fewer antimicrobial
      treatments than control and placebo calves. The results indicated that calf
      diarrhea was associated with low serum IgG levels and low-weight calves. Grain
      consumption and weight gain over the first 28 d of life were significantly
      greater in colostrum-supplemented calves compared with control calves. No
      differences in mortality or respiratory disease incidence among groups were
      detected. Supplemental colostrum during the first 2 wk of life can reduce
      diarrheal disease in preweaned calves on calf ranches and thereby reduce the
      amount of antimicrobial treatments needed.

PMID- 19109288
TI  - Comparative effects of two oral rehydration solutions on milk clotting, abomasal
      luminal pH, and abomasal emptying rate in suckling calves.
AB  - The effect of adding an oral rehydration therapy (ORT) solution containing
      bicarbonate, citrate, and acetate to cow's milk on milk clotting, abomasal
      luminal pH, and abomasal emptying rate was determined in suckling calves. Six
      male Holstein-Friesian calves with abomasal cannulae, 5 to 13 d of age, were used
      in a crossover design. Calves were fed 2 L of cow's milk alone, milk with an ORT
      solution containing a low bicarbonate concentration (25 mmol/L), acetate (12
      mmol/L), citrate (12 mmol/L), and glycine (7 mmol/L; group BACG), or milk with an
      ORT solution containing formate (58 mmol/L) and acetate (15 mmol/L) in randomized
      order. Clotting of milk was assessed in vivo and in vitro. Abomasal luminal pH
      was monitored continuously. Abomasal emptying rates were determined by using the
      change in abomasal luminal pH, acetaminophen absorption, and glucose absorption.
      The addition of a BACG-ORT solution to cow's milk increased in vitro clotting
      time by approximately 6 min. All 3 test solutions clotted in vivo by 15 min after
      the beginning of suckling. The addition of a BACG-ORT solution to cow's milk
      increased the pH of cow's milk and abomasal fluid by approximately 0.3 pH units.
      The addition of a BACG-ORT or a formate and acetate-ORT solution to cow's milk
      increased solution osmolality and slowed the rate of abomasal emptying. We
      concluded that the addition of BACG-ORT solution to cow's milk did not affect
      milk clotting in vivo. Recommendations based on the results of in vitro studies
      that bicarbonate- or citrate-containing ORT solutions should not be fed
      concurrently with cow's milk do not appear to be relevant to in vivo conditions
      when 2 L of a low-bicarbonate (25 mmol/L), low-citrate (12 mmol/L) ORT solution
      is fed.

PMID- 19109289
TI  - Intake and milk production of cows fed diets that differed in dietary neutral
      detergent fiber and neutral detergent fiber digestibility.
AB  - The objectives of this study were to determine how feeding diets that differed in
      dietary neutral detergent fiber (NDF) concentration and in vitro NDF
      digestibility affects dry matter (DM) intake, ruminal fermentation, and milk
      production in early lactation dairy cows. Twelve rumen-cannulated, multiparous
      Holstein cows averaging 38 +/- 15 d (+/-standard deviation) in milk, and
      producing 40 +/- 9 kg of milk daily, were used in a replicated 4 x 4 Latin square
      design with 28-d periods. Treatment diets were arranged in a 2 x 2 factorial with
      28 or 32% dietary NDF (DM basis) and 2 levels of straw NDF digestibility: 1) LD,
      untreated wheat straw (77% NDF, 41% NDF digestibility) or 2) HD, anhydrous NH(3)
      treated wheat straw (76% NDF, 62% NDF digestibility). All 4 diets consisted of
      wheat straw, alfalfa silage, corn silage, and a concentrate mix of cracked corn
      grain, corn gluten meal, 48% soybean meal, and vitamins and minerals. Wheat straw
      comprised 8.5% DM of the 28% NDF diets and 16% DM of the 32% NDF diets. Cows fed
      28% NDF and HD diets produced more milk, fat, and protein than those consuming
      32% NDF or LD diets. Dry matter intake was greater for cows consuming 28% NDF
      diets, but intakes of DM and total NDF were not affected by in vitro NDF
      digestibility. Intake of digestible NDF was greater for cows consuming HD diets.
      Ruminal fermentation was not affected by feeding diets that differed in NDF
      digestibility. Ruminal NDF passage rate was slower for cows fed HD than LD. No
      interactions of dietary NDF concentration and in vitro NDF digestibility were
      observed for any parameter measured. Regardless of dietary NDF concentration,
      increased in vitro NDF digestibility improved intake and production in early
      lactation dairy cows.

PMID- 19109290
TI  - Meta-analysis of the effect of oral selenium supplementation on milk selenium
      concentration in cattle.
AB  - Soils in many regions of the world have a low Se content. Consequently, forages
      and crops grown on these soils may provide inadequate dietary Se for humans and
      grazing animals. Selenium supplementation has been used to enhance Se status and
      milk Se concentration, but results conflict. Milk Se concentration appears to be
      a useful indicator of animal and herd Se status, and reflects the responsiveness
      to supplementation. A systematic review and meta-analysis were carried out to
      summarize all available scientific evidence for the effect of oral Se
      supplementation on milk Se concentration in cattle. The literature search was
      based on electronic and nonelectronic databases. Fixed- and random-effects models
      of meta-analysis were used, and a meta-regression was carried out to evaluate
      heterogeneity among studies. Random-effects meta-analysis was performed on 42
      studies published between 1977 and 2007. Oral Se supplementation resulted in an
      average increase in milk Se content of 0.16 (95% confidence interval: 0.117,
      0.207) micromol/L, with a significant heterogeneity among studies. Weak
      publication bias was evident, but it did not change the average effect. The
      continent where the study was performed, Se source, Se dose, and the interaction
      between source and dose explained 71% of the between-study variance. On average,
      American cows supplemented with Se yeast (e.g., 6 mg/h per day) had greater milk
      Se concentrations (approximately 0.37 micromol/L) 75 d after the beginning of
      supplementation when compared with those supplemented with inorganic forms of Se.
      This information provides a basis for tailoring daily animal requirements and for
      enhancing the Se intake of consumers of dairy products.

PMID- 19109291
TI  - The effects of live yeast supplementation to dairy cows during the hot season on
      production, feed efficiency, and digestibility.
AB  - The current study examined the effects of live yeast (LY) supplementation to
      dairy cows during the summer season on milk production, feed efficiency and
      ration digestibility. Forty-two dairy cows (14 primiparous and 28 multiparous)
      were fed either a control lactating diet or supplemented with 1 g of LY
      (Saccharomyces cerevisiae, Biosaf, Lesaffre) per 4 kg of dry matter consumed. The
      LY amounts were adjusted twice a week. Four rumen samples were taken from 30 cows
      in 2-h periods and ammonia concentrations were determined. Fecal grab samples
      from 30 cows were collected during 3 consecutive days, to determine the apparent
      digestibility of diets. The daily dry matter intake in the LY group was 2.5%
      greater compared with the control group (24.7 and 24.1 kg, respectively). The
      daily average milk yield of the LY group was greater by 1.5 kg (4.1%) compared
      with the control group (37.8 vs. 36.3 kg, respectively). There were no
      significant differences in the milk fat and protein percentages, but fat yield
      was greater in the LY group than in the control. The fat-corrected milk 4% was
      2.0 kg (6.1%) greater in the LY group than in the control group (34.8 vs. 32.8
      kg, respectively). The efficiency of using dry matter to produce 4% fat-corrected
      milk was 3.7% greater in the LY group compared with the control group. The
      ruminal ammonia concentrations after feeding were greater in the control group
      than in the LY group (151.9 vs. 126.1 mg/l, respectively). No differences were
      observed among groups in the total tract apparent digestibility of dry matter and
      other diet components. The pH values in the rumen that were determined in a
      companion trial using 4 fistulated cows tended to be higher in cows that were
      supplemented with LY than in the control (6.67 vs. 6.54, respectively). It may be
      concluded that LY supplementation to dairy cows during the hot season improved
      the rumen environment in a way that increased the dry matter intake and in
      consequence enhanced the productivity and efficiency.

PMID- 19109292
TI  - Effect of a low-moisture buffer block on ruminal pH in lactating dairy cattle
      induced with subacute ruminal acidosis.
AB  - The objective of this study was to evaluate the effect of a low-moisture buffer
      block on ruminal pH and milk production in cows induced with subacute ruminal
      acidosis (SARA). Sixteen ruminally cannulated cows were randomly assigned to
      treatment (access to buffer blocks) or control (no buffer blocks). Ruminal pH was
      recorded each minute; dry matter intake (DMI), milk yield, and milk composition
      were measured daily. The experiment lasted 12 d and consisted of a 3-d pre-SARA
      period (without access to buffer blocks; d 1 to 3), after which 8 cows were given
      access to buffer blocks and 8 cows continued without access to buffer blocks. The
      next 4 d (d 4 to 7) were for evaluating the response to buffer blocks. On d 8,
      cows were restricted to 50% of previous DMI, and on d 9 SARA was induced
      (addition of 4 kg of wheat/barley pellet to pre-SARA total mixed ration (TMR).
      Cows were then monitored for a 3-d recovery period (d 10 to 12). The SARA
      challenge was successful in decreasing mean ruminal pH and time and area below pH
      5.6. Intake of buffer blocks averaged 0.33 kg of DM/cow per day and was greatest
      on d 4 and d 8. Total DMI (TMR plus buffer block) and yields of milk and milk
      components were not affected by treatment. Although there was no overall effect
      of treatment on any of the ruminal pH variables measured, there were significant
      treatment by period interactions for several ruminal pH variables. Cows on the
      control treatment tended to experience a greater decrease in mean ruminal pH when
      induced with SARA than cows with access to buffer blocks (-0.55 vs. -0.20 pH
      units). Cows on the control treatment also experienced a greater increase in time
      (9.7 vs. 4.1 h/d) and area (249 vs. 83 min x pH units/d) below pH 5.6 compared
      with cows with access to buffer blocks. Ruminal volatile fatty acids, lactate,
      ethanol, and succinate concentrations during the SARA challenge did not differ
      between treatments. Eating behavior was not affected by treatment. Size of the
      first meal of the day was greater on the SARA challenge day than during the pre
      SARA period (11.0 vs. 5.7 kg, as fed). Giving cows access to a buffer-containing
      molasses block may reduce the duration and the severity of a 1-d SARA challenge.

PMID- 19109293
TI  - Short communication: analysis of immune function in lactating dairy cows fed
      diets varying in phosphorus content.
AB  - The aim of this study was to evaluate the effect of varying dietary P on bovine
      immune function. Nine first- or second-lactation Holstein cows were fed diets
      varying in P in a 3 x 3 Latin square design. Diets were formulated to contain
      either low (0.34%, no supplementary P), medium (0.43%), or high (0.52%) P. All 3
      diets were formulated to meet or exceed current NRC requirements for P content.
      Between d 21 and 26 of each period, blood samples were collected and serum
      inorganic P concentration, lymphocyte proliferation, and neutrophil bactericidal
      activity were measured. Serum P increased with increasing dietary P intake and
      was greatest in the first lactation compared with subsequent lactations. There
      was a stage of lactation-dependent increase in lymphocyte proliferation after
      stimulation with concanavalin A, phytohemagglutinin, or pokeweed mitogen.
      However, dietary P did not alter lymphocyte proliferation or neutrophil
      bactericidal activity in vitro. In conclusion, decreasing dietary P to reduce
      manure P content and the risk of P losses from farms to surface water does not
      have an adverse effect on the innate or cell-mediated immune responses of
      lactating dairy cattle.

PMID- 19109294
TI  - The number of single nucleotide polymorphisms and on-farm data required for whole
      herd parentage testing in dairy cattle herds.
AB  - New platforms utilizing single nucleotide polymorphisms (SNP) offer operational
      advantages over the conventional microsatellite-based ones, making them a
      promising alternative for parentage exclusion. Through simulation and empirical
      data, a 40-SNP panel (where the minor allele frequency was 0.35 on average) was
      shown to be a comparable or better diagnostic tool than the current 14
      microsatellite panel that is used to parentage test New Zealand dairy animals.
      The 40 SNP alone did not have sufficient power of exclusion to match more than
      75% of the progeny to the correct sire and dam. Utilizing mating records and
      grouping progeny and dams by birth and calving dates, respectively, decreased the
      number of sire-dam combinations that each progeny was tested against and
      dramatically increased the utility of the SNP. These results highlight the
      importance of combining genotypes with on-farm data to maximize the ability to
      assign parentage in the New Zealand dairy herd.

PMID- 19109296
TI  - Economic evaluation of genomic breeding programs.
AB  - The objective of this study was to compare a conventional dairy cattle breeding
      program characterized by a progeny testing scheme with different scenarios of
      genomic breeding programs. The ultimate economic evaluation criterion was
      discounted profit reflecting discounted returns minus discounted costs per cow in
      a balanced breeding goal of production and functionality. A deterministic
      approach mainly based on the gene flow method and selection index calculations
      was used to model a conventional progeny testing program and different scenarios
      of genomic breeding programs. As a novel idea, the modeling of the genomic
      breeding program accounted for the proportion of farmers waiting for daughter
      records of genotyped young bulls before using them for artificial insemination.
      Technical and biological coefficients for modeling were chosen to correspond to a
      German breeding organization. The conventional breeding program for 50 test bulls
      per year within a population of 100,000 cows served as a base scenario. Scenarios
      of genomic breeding programs considered the variation of costs for genotyping,
      selection intensity of cow sires, proportion of farmers waiting for daughter
      records of genotyped young bulls, and different accuracies of genomic indices for
      bulls and cows. Given that the accuracies of genomic indices are greater than
      0.70, a distinct economic advantage was found for all scenarios of genomic
      breeding programs up to factor 2.59, mainly due to the reduction in generation
      intervals. Costs for genotyping were negligible when focusing on a population
      wide perspective and considering additional costs for herdbook registration, milk
      recording, or keeping of bulls, especially if there is no need for yearly
      recalculation of effects of single nucleotide polymorphisms. Genomic breeding
      programs generated a higher discounted profit than a conventional progeny testing
      program for all scenarios where at least 20% of the inseminations were done by
      genotyped young bulls without daughter records. Evaluation of levels of annual
      genetic gain for individual traits revealed the same potential for low heritable
      traits (h(2) = 0.05) compared with moderate heritable traits (h(2) = 0.30),
      preconditioning highly accurate genomic indices of 0.90. The final economic
      success of genomic breeding programs strongly depends on the complete abdication
      of any forms of progeny testing to reduce costs and generation intervals, but
      such a strategy implies the willingness of the participating milk producers.

PMID- 19109297
TI  - Genetic parameters for conjugated linoleic acid, selected milk fatty acids, and
      milk fatty acid unsaturation of Italian Holstein-Friesian cows.
AB  - The objective of this study was to estimate genetic parameters for conjugated
      linoleic acid (CLA) and other selected milk fatty acid (FA) content and for
      unsaturation ratios in the Italian Holstein Friesian population. Furthermore, the
      relationship of milk FA with milk fat and protein content was considered. One
      morning milk sample was collected from 990 Italian Holstein Friesian cows
      randomly sampled from 54 half-sib families, located in 34 commercial herds in the
      North-eastern part of Italy. Each sample was analyzed for milk percentages of fat
      and protein, and for single FA percentages (computed as FA weight as a proportion
      of total fat weight). Heritabilities were moderate for unsaturated FA, ranging
      from 0.14 for C16:1 to 0.19 for C14:1. Less than 10% of heritability was
      estimated for each saturated FA content. Heritability for index of desaturation,
      monounsaturated FA and CLA/trans-11 18:1 ratio were 0.15, 0.14, and 0.15,
      respectively. Standard errors of the heritability values ranged from 0.02 to
      0.06. Genetic correlations were high and negative between C16:0 and C18:0, as
      well as between C14:0 and C18:0. Genetic correlations of index of desaturation
      were high and negative with C14:0 and C16:0 (-0.70 and -0.72, respectively), and
      close to zero (0.03) with C18:0. The genetic correlation of C16:0 with fat
      percentage was positive (0.74), implying that selection for fat percentage should
      result in a correlated increase of C16:0, whereas trans-11 C18:1 and cis-9, trans
      11 C18:2 contents decreased with increasing fat percentage (-0.69 and -0.55,
      respectively). Genetic correlations of fat percentage with 14:1/14 and 16:1/16
      ratios were positive, whereas genetic correlations of fat percentage with 18:1/18
      and CLA/trans-11 18:1 ratios were negative. These results suggest that it is
      possible to change the milk FA composition by genetic selection, which offers
      opportunities to meet consumer demands regarding health aspects of milk and dairy
      products.

PMID- 19109295
TI  - Antibody response against three widespread bovine viruses is not impaired in
      Holstein cattle carrying bovine leukocyte antigen DRB3.2 alleles associated with
      bovine leukemia virus resistance.
AB  - Due to the wide dissemination of bovine leukemia virus (BLV) infection among
      dairy cattle, control and eradication programs based on serological detection of
      infected cattle and subsequent culling face a major economic task. In Argentina,
      genetic selection of cattle carrying alleles of the bovine leukocyte antigen
      (BoLA) DRB3.2 gene associated with BLV-infection resistance, like *0902, emerges
      as the best additional tool toward controlling virus spread. A potential risk in
      expanding or segregating BoLA selected populations of cattle is that it might
      increase susceptibility to other common viruses. Special concern raises the
      strong association found between low proviral load and low antibody titer against
      major BLV structural proteins. This phenomenon might depend on host genetic
      factors influencing other viruses requiring, unlike BLV, strong and long-lasting
      humoral immune response to prevent infection. In this study, we demonstrate that
      there is no association among neutralizing antibody titers against foot and mouth
      disease virus, bovine viral diarrhea virus, or bovine herpesvirus type 1 and
      polymorphism of the BoLA DRB3.2 gene. Conversely, there is strong association
      between BoLA DRB3.2*0902 and low antibody titers against 2 BLV structural
      proteins--env gp51 and gag p24--to date, the best BLV resistance marker. There is
      also significant association between low antibody titers against gp51 and p24 and
      BoLA DRB3.2*1701 and low antibody titers against p24 and BoLA DRB3.2*1101 or 02.
      Our data suggest that increasing BoLA-selected BLV-resistant cattle or
      segregating BoLA-associated alleles to BLV susceptibility would not affect the
      resistance or the predisposition to bovine viral diarrhea virus, bovine
      herpesvirus type 1, or foot and mouth disease virus infection.

PMID- 19109298
TI  - Effects of chemical composition variation on the dynamics of ruminal fermentation
      and biological value of corn milling (co)products.
AB  - The objectives of this study were to evaluate the dynamics of gas production of
      several corn (co)products, to develop equations to predict the rate of ruminal
      fiber digestion, to estimate total digestible nutrients (TDN) and net energy for
      lactation (NE(L)), and to assess the stochasticity of chemical composition and
      nutritive value variability. Four corn milling (co)products were evaluated in
      this study: high protein dried distillers grains (HP-DDG), corn bran (BRAN) and
      dehydrated germ (GERM), and a dried distillers grains plus soluble produced with
      a low-heat drying process (BPX). Alfalfa hay was used as an internal standard
      feed in the in vitro fermentation dynamics analysis. Standard chemical analyses,
      in vitro digestibility, and in vitro gas production techniques were used to
      obtain the necessary physicochemical characterization of feeds. The in vitro dry
      matter digestibility at 24 and 48 h of incubation decreased exponentially as acid
      detergent insoluble nitrogen increased. However, the degree of in vitro dry
      matter digestibility reduction was more accentuated at 24 than at 48 h of
      incubation. The difference among these feeds regarding the dynamics of the
      anaerobic fermentation within different substrates (intact feed, and fiber and
      defatted residues) was evaluated. Results suggested that the proportion of fiber
      digested in the rumen was affected by the degree of sample processing and fat
      removal. Fractional fermentation rate (kf) of neutral detergent residue (without
      sodium sulfite) and defatted fiber residue for BRAN, GERM, HP-DDG, and BPX was
      estimated to be 0.0635 and 0.0852 h(-1), 0.0803 and 0.0914 h(-1), 0.118 and 0.117
      h(-1), and 0.0695 and 0.0844 h(-1), respectively. The most influential variables
      affecting kf(NDR) of HP-DDG and BPX also affected the predicted TDN, suggesting
      that fiber quality is essential to ensure higher TDN values for these feeds. Our
      study indicated that it is possible to routinely quantify the rate of fiber
      digestion and this approach may be based on common analytical procedures namely
      estimates of neutral detergent fiber, acid detergent fiber, acid detergent
      insoluble nitrogen, ether extract, and acid detergent lignin. Our simulations of
      TDN values demonstrated that differences in fermentability and chemical
      composition of these corn (co)products might considerably affect the supply of
      energy to lactating dairy cow. The analytical methods developed in this study may
      serve as a valuable tool to assess nutrient quality and uniformity when samples
      differ in chemical composition.

PMID- 19109299
TI  - Effect of pregrazing herbage mass and pasture allowance on the lactation
      performance of Holstein-Friesian dairy cows.
AB  - The objective of this study was to investigate the effect of pregrazing herbage
      mass (HM) and pasture allowance (PA) on the grazing management and lactation
      performance of spring-calving dairy cows. Sixty-eight Holstein-Friesian dairy
      cows (mean calving date, February 6) were randomly assigned across 4 treatments
      (n = 17) in a 2 x 2 factorial arrangement. The 4 treatments consisted of 2
      pregrazing HM (>4 cm) and 2 PA (>4 cm): 1,700 kg of dry matter (DM)/ha (medium,
      M) or 2,200 kg of DM/ha (high, H), and 16 or 20 kg of pasture DM/cow per day. The
      experimental period lasted 30 wk. The experimental area was divided into 4
      farmlets, with 1 farmlet per treatment. Mean HM throughout the experimental
      period was 1,767 kg of DM/ha (M HM) compared with 2,358 kg of DM/ha (H HM).
      Offering an M HM sward resulted in significantly greater milk protein yield
      (+31.7 g/d) and lower mean body weight (-12.8 kg). The body condition score
      change was significantly smaller (-0.21) with the M HM treatments compared with
      the H HM treatment (-0.34). Milk solids output per hectare was 6% greater on the
      M HM treatments compared with the H HM treatments. Increasing PA significantly
      increased milk (+0.9 kg/d), solids-corrected milk (+0.7 kg/d), protein (+43.9
      g/d), and lactose (+52.7 g/d) yields. Mean body weight was also significantly
      greater for cows offered 20 kg of PA (+11.4 kg/cow). It was concluded that in
      rotational grazing systems, adapting the concept of grazing M HM pastures (1,700
      kg of DM/ha) will result in increased sward quality and increased milk solids
      output per hectare. At medium levels of pregrazing HM, offering animals 20 kg of
      DM PA will result in increased milk yield per cow.

PMID- 19109300
TI  - Prediction of coagulation properties, titratable acidity, and pH of bovine milk
      using mid-infrared spectroscopy.
AB  - This study investigated the potential application of mid-infrared spectroscopy
      (MIR 4,000-900 cm(-1)) for the determination of milk coagulation properties
      (MCP), titratable acidity (TA), and pH in Brown Swiss milk samples (n = 1,064).
      Because MCP directly influence the efficiency of the cheese-making process, there
      is strong industrial interest in developing a rapid method for their assessment.
      Currently, the determination of MCP involves time-consuming laboratory-based
      measurements, and it is not feasible to carry out these measurements on the large
      numbers of milk samples associated with milk recording programs. Mid-infrared
      spectroscopy is an objective and nondestructive technique providing rapid real
      time analysis of food compositional and quality parameters. Analysis of milk
      rennet coagulation time (RCT, min), curd firmness (a(30), mm), TA (SH degrees/50
      mL; SH degrees = Soxhlet-Henkel degree), and pH was carried out, and MIR data
      were recorded over the spectral range of 4,000 to 900 cm(-1). Models were
      developed by partial least squares regression using untreated and pretreated
      spectra. The MCP, TA, and pH prediction models were improved by using the
      combined spectral ranges of 1,600 to 900 cm(-1), 3,040 to 1,700 cm(-1), and 4,000
      to 3,470 cm(-1). The root mean square errors of cross-validation for the
      developed models were 2.36 min (RCT, range 24.9 min), 6.86 mm (a(30), range 58
      mm), 0.25 SH degrees/50 mL (TA, range 3.58 SH degrees/50 mL), and 0.07 (pH, range
      1.15). The most successfully predicted attributes were TA, RCT, and pH. The model
      for the prediction of TA provided approximate prediction (R(2) = 0.66), whereas
      the predictive models developed for RCT and pH could discriminate between high
      and low values (R(2) = 0.59 to 0.62). It was concluded that, although the models
      require further development to improve their accuracy before their application in
      industry, MIR spectroscopy has potential application for the assessment of RCT,
      TA, and pH during routine milk analysis in the dairy industry. The implementation
      of such models could be a means of improving MCP through phenotypic-based
      selection programs and to amend milk payment systems to incorporate MCP into
      their payment criteria.

PMID- 19109301
TI  - CHOTTO1, a double AP2 domain protein of Arabidopsis thaliana, regulates
      germination and seedling growth under excess supply of glucose and nitrate.
AB  - Arabidopsis chotto1 (cho1) mutants show resistance to (-)-R-ABA, an ABA analog,
      during germination and seedling growth. Here, we report cloning and
      characterization of the CHO1 gene. cho1 mutants showed only subtle resistance to
      (+)-S-ABA during germination. The cho1 mutation acts as a strong enhancer of the
      abi5 mutant, whereas the cho1 abi4 double mutant showed ABA resistance similar to
      the abi4 single mutant. This suggests that CHO1 and ABI4, but not ABI5, act in
      the same genetic pathway. Map-based cloning revealed that the CHO1 gene encodes a
      putative transcription factor containing double AP2 domains. The CHO1 gene was
      expressed predominantly in seed, with the strongest expression in imbibed seed.
      Induction of CHO1 expression was observed 4 h after seed imbibition and reached a
      maximum level at 24 h. Induction of CHO1 expression did not occur in the abi4
      mutants, indicating that this is an ABI4-dependent process. Microarray
      experiments showed that a large number of genes involved in primary metabolism
      and the stress response were up-regulated in the cho1 mutant. Growth of abi4 and
      cho1 mutant seedlings was resistant to high concentrations of glucose. In
      addition, growth of cho1 mutant seedlings was partially resistant to excess
      nitrate (50 mM), as evident from their expanded green cotyledons. However, their
      growth was normal under moderate nitrate concentrations (< 10 mM). This nitrate
      response was specific to the cho1 mutants and was not observed in the abi4
      mutants. Taken together, our results indicate that CHO1 regulates nutritional
      responses downstream of ABI4 during germination and seedling growth.

PMID- 19109302
TI  - Photosynthetic carbon assimilation in the coccolithophorid Emiliania huxleyi
      (Haptophyta): Evidence for the predominant operation of the c3 cycle and the
      contribution of {beta}-carboxylases to the active anaplerotic reaction.
AB  - The coccolithophorid Emiliania huxleyi (Haptophyta) is a representative and
      unique marine phytoplankton species that fixes inorganic carbon by photosynthesis
      and calci-fication. We examined the initial process of photosynthetic carbon
      assimilation by analyses of metabolites, enzymes and genes. When the cells were
      incubated with a radioactive substrate (2.3 mM NaH(14)CO(3)) for 10 s under
      illumination, 70% of the (14)C was incorporated into the 80% methanol-soluble
      fraction. Eighty-five and 15% of (14)C in the soluble fraction was incorporated
      into phosphate esters (P-esters), including the C(3) cycle intermediates and a
      C(4) compound, aspartate, respectively. A pulse-chase experiment showed that
      (14)C in P-esters was mainly transferred into lipids, while [(14)C]aspartate,
      [(14)C]alanine and [(14)C]glutamate levels remained almost constant. These
      results indicate that the C(3) cycle functions as the initial pathway of carbon
      assimilation and that beta-carboxylation contributes to the production of amino
      acids in subsequent metabolism. Transcriptional analysis of beta-carboxylases
      such as pyruvate carboxylase (PYC), phosphoenolpyruvate carboxylase (PEPC) and
      phosphoenolpyruvate carboxykinase (PEPCK) revealed that PYC and PEPC transcripts
      were greatly increased under illumination, whereas the PEPCK transcript decreased
      remarkably. PEPC activity was higher in light-grown cells than in dark-adapted
      cells. PYC activity was detected in isolated chloroplasts of light-grown cells.
      According to analysis of their deduced N-terminal sequence, PYC and PEPC are
      predicted to be located in the chloroplasts and mitochondria, respectively. These
      results suggest that E. huxleyi possesses unique carbon assimila-tion mechanisms
      in which beta-carboxylation by both PYC and PEPC plays important roles in
      different organelles.

PMID- 19109303
TI  - Simulation of DNA sequence evolution under models of recent directional
      selection.
AB  - Computer simulation is an essential tool in the analysis of DNA sequence
      variation for mapping events of recent adaptive evolution in the genome. Various
      simulation methods are employed to predict the signature of selection in sequence
      variation. The most informative and efficient method currently in use is
      coalescent simulation. However, this method is limited to simple models of
      directional selection. Whole-population forward-in-time simulations are the
      alternative to coalescent simulations for more complex models. The notorious
      problem of excessive computational cost in forward-in-time simulations can be
      overcome by various simplifying amendments. Overall, the success of simulations
      depends on the creative application of some population genetic theory to the
      simulation algorithm.

PMID- 19109304
TI  - Pulse pressure/stroke volume: a surrogate index of arterial stiffness and the
      relation to segmental relaxation and longitudinal systolic deformation in
      hypertensive disease.
AB  - AIMS: Pulse pressure/stroke volume (PP/SV) is regarded as a surrogate index of
      arterial stiffness (AS). Strain echocardiography is a novel method to evaluate
      systolic and diastolic left ventricular (LV) function. The aim of this study was
      to investigate the effect of AS on segmental relaxation and systolic deformation
      in hypertensive disease. METHODS AND RESULTS: We evaluated 70 hypertensive
      patients and 30 non-hypertensive volunteers. The patients were divided as
      follows: without global diastolic dysfunction (HTN-N) and with global diastolic
      dysfunction (HTN-DD). The segmental and global longitudinal strain (S) and strain
      rate (SR) and early and late diastolic SR were recorded from 18 segments. The
      number of segments with abnormal relaxation (SR(E)/SR(A) < 1.1) was calculated as
      segmental DD. Pulse pressure/SV index was used as a surrogate marker of AS.
      Arterial stiffness was higher in HTN-N and was more pronounced in the HTN-DD
      group compared with the control (1.45 +/- 0.38 vs. 1.79 +/- 0.36 vs.1.21 +/- 0.31
      mmHg m2/ml, all P < 0.05). HTN-N had increased segmental DD compared to control
      despite the normal conventional indices of diastolic dysfunction. Global
      longitudinal deformation of the HTN-N group was similar to the control; HTN-DD
      also showed evidence of LV hypertrophy (LVH) and had more extensive segmental DD
      and deteriorated global systolic deformation compared with the control, despite
      the normal ejection fraction (segmental DD: 11 +/- 3 vs. 4 +/- 2, P < 0.05 and
      strain: 17.7 +/- 2.8 vs. 21.2 +/- 2.3%, P < 0.05). The deterioration of AS in the
      hypertensive group was accompanied with a particular distribution of segmental DD
      that was more pronounced at the basal regions compared with apical LV
      territories. Arterial stiffness and LV mass index are found to be independent
      predictors of segmental DD, mean Ea, and global systolic deformation. CONCLUSION:
      Arterial stiffness and LVH are independently related to abnormal segmental
      relaxation and global longitudinal systolic deformation in hypertensive disease.

PMID- 19109306
TI  - Challenges and strategies for targeted phosphorylation site identification and
      quantification using mass spectrometry analysis.
AB  - Despite its importance, the 'ultimate' method to identify and quantify site
      specific protein phosphorylation using mass spectrometry (MS) has yet to be
      established. This is as much a function of the dynamic range of instrumentation
      as it is the complexities surrounding the isolation and behavior of
      phosphopeptides. Phosphorylation site analysis using MS can be quite challenging
      when analyzing just one protein and quickly becomes a daunting task when
      attempting to perform proteome-wide measurements. Data-dependent tandem MS-based
      methods which are useful for the discovery and characterization of novel
      phosphorylation sites often lack the dynamic range and quantitative aspect
      required for studying the temporal phases of phosphorylation. While targeted
      methods such as multiple reaction monitoring do provide a highly specific and
      quantitative methodology for studying phosphorylation changes over time, they are
      not suited for initial discovery of previously unreported sites of
      phosphorylation. Data-independent acquisition represents a relatively new
      approach for simultaneous qualitative and quantitative sample analysis which
      holds promise for filling this technological gap.

PMID- 19109305
TI  - Targeted proteomics for validation of biomarkers in clinical samples.
AB  - The rapid rise and application of proteomic technologies has resulted in an
      exponential increase in the number of proteins that have been discovered and
      presented as 'potential' biomarkers for specific diseases. Unfortunately, the
      number of biomarkers approved for use by the Food and Drug Administration has not
      risen in likewise manner. While there are a number of reasons for this
      discrepancy, this glut of 'potential' biomarkers also indicates the need for
      validation methods to confirm or refute their utility in clinical diagnostics.
      For this reason, the emphasis on developing methods to target and measure the
      absolute quantity of specific proteins and peptides in complex proteomic samples
      has grown.

PMID- 19109307
TI  - Big fish in the genome era.

PMID- 19109309
TI  - Emerging gene knockout technology in zebrafish: zinc-finger nucleases.
AB  - One advantage of the zebrafish model system is the ability to use forward
      genetics to reveal critical gene functions by their mutant phenotype. Reverse
      genetic tools are available, although it is more challenging and time-consuming
      to identify mutations in specific genes of interest and virtually impossible to
      induce mutations in a targeted manner. Two recent papers have shown that locus
      specific zinc-finger nucleases (ZFNs) can be used to create mutations in
      investigator-specified loci at high frequency, generating considerable enthusiasm
      that the technology may be generally applicable to many zebrafish genes. The rate
      limiting step in ZFN application is typically the zinc-finger protein (ZFP)
      design phase, partly because ZFPs that bind to intended target sequences in naked
      DNA may not recognize the target within chromatin, or may recognize cryptic
      sites. Importantly, both papers also provide new tools to validate or pre-select
      ZFNs that work well in vivo and thus greatly facilitate the identification of
      active ZFNs. Finally, work in other model systems and in cultured cells show that
      ZFNs can facilitate homology-directed repair, raising the exciting possibility
      that ZFNs may facilitate homologous recombination in zebrafish, allowing site
      specific modification of endogenous genes via a method that does not require
      embryonic stem cell technology.

PMID- 19109310
TI  - Can the outcome of the next pregnancy be predicted at the time of induced
      abortion?
AB  - BACKGROUND: Factors predicting the outcome of the next pregnancy following
      termination of pregnancy (TOP) are poorly known. METHODS: A cohort of 1269 women
      undergoing medical TOP between 2000 and 2002 were followed up until the next
      pregnancy or until the end of 2006, using registers of induced abortion, births
      and hospital discharges. Factors associated with repeat TOP, delivery and failed
      pregnancy were analysed. RESULTS: During the mean (+/-SD) follow-up period of 4.2
      +/- 1.5 years, 446 (35%) women had at least one subsequent pregnancy. Of these,
      207 (46%) resulted in delivery, 169 (38%) in repeat TOP and 16% in failed
      pregnancy. In multivariate analysis, parity [hazard ratio (HR) 3.42, 95%
      confidence interval (CI) 1.70-6.91] and history of TOP (HR 1.60, 95% CI 1.10
      2.33) were risk factors of repeat TOP. Age above 25 years (HR < or = 0.46) and
      the use of intrauterine contraception (HR < or = 0.45) were associated with
      reduced risks of repeat TOP. However, only age between 25 and 29 years was
      associated with an increased probability of delivery (HR 2.44, 95% CI 1.45-4.11).
      CONCLUSIONS: Risk factors of repeat TOP are more clearly defined than factors
      associated with delivery. An increased focus on young women, those with a history
      of TOP and parous women, might be effective in reducing repeat TOP.

PMID- 19109308
TI  - Transposon tools hopping in vertebrates.
AB  - In the past decade, tools derived from DNA transposons have made major
      contributions to vertebrate genetic studies from gene delivery to gene discovery.
      Multiple, highly complementary systems have been developed, and many more are in
      the pipeline. Judging which DNA transposon element will work the best in diverse
      uses from zebrafish genetic manipulation to human gene therapy is currently a
      complex task. We have summarized the major transposon vector systems active in
      vertebrates, comparing and contrasting known critical biochemical and in vivo
      properties, for future tool design and new genetic applications.

PMID- 19109312
TI  - Proprotein convertase subtilisin/kexin type 4 in mammalian fertility: a review.
AB  - BACKGROUND: Proprotein convertase subtilisin/kexin type 4 (PCSK4), also known as
      proprotein convertase 4, belongs to a family of endoproteinases involved in the
      proteolytic conversion of secretory precursor proteins to their active forms. Its
      amino acid sequence is highly conserved in mammals, an indication of its
      biological importance. METHODS: We have searched PubMed and molecular biology
      databases for information relating to the structure, expression and biological
      functions of PCSK4. RESULTS: PCSK4 is predominantly expressed in male germ cells
      and located on the plasma membrane overlying the acrosome of sperm. It is also
      present in ovary and placenta. Inactivation of its gene in mouse does not alter
      spermatogenesis, but renders sperm incapable of fertilizing oocytes. This
      incapacity results in part from sperm susceptibility to a premature acrosome
      reaction and their reduced ability to bind to the zona pellucida. In female mice,
      a lack of PCSK4 causes subfertility associated with impaired folliculogenesis. In
      addition, this enzyme has been shown to stimulate the invasiveness of human
      placental trophoblasts in culture, suggesting that it may facilitate placentation
      in vivo. CONCLUSIONS: PCSK4 appears to be a crucial enzyme for reproduction.
      Alterations of PCSK4 expression or activity could be the underlying cause of some
      unexplained cases of human infertility. Conversely, inactivation of this protease
      represents a potential strategy for non-hormonal contraception.

PMID- 19109311
TI  - The role of kisspeptin in the control of gonadotrophin secretion.
AB  - BACKGROUND: Kisspeptins, and their cognate receptor gpr-54, were first found to
      regulate the hypothalamic-pituitary-gonadal (HPG) axis in 2003, when two groups
      demonstrated that mutations in gpr-54 cause idiopathic hypogonadotropic
      hypogonadism characterized by delayed or absent puberty. This review aims to
      highlight discoveries in the KiSS-1/gpr-54 system, focusing on their regulation
      of the HPG axis in male and female reproductive systems of both mammalian and non
      mammalian vertebrates. METHODS: A search of PUBMED and the authors' files was
      done without limitations by language or species for citations relevant to
      kisspeptin, reproduction and signal transduction. RESULTS: Kisspeptins and gpr-54
      are critical for puberty and the regulation of reproduction. Kisspeptins have
      been implicated in mediating many of the important signals relayed to the
      gonadotrophin-releasing hormone (GnRH) neuron such as positive and negative
      feedback, metabolic input and photoperiod. The ability of kisspeptin neurons to
      co-ordinate different signals impinging on the HPG axis makes it one of the most
      important regulators of GnRH and the reproductive axis. CONCLUSIONS: Kisspeptins
      are pivotal regulators of the HPG axis and reproduction, with the ability to
      integrate signals from both internal and external sources. Knowledge about the
      signalling mechanisms involved in kisspeptin stimulation of GnRH would help
      improve the understanding of the importance of this critical pathway in
      reproduction.

PMID- 19109313
TI  - Techniques for cryopreservation of individual or small numbers of human
      spermatozoa: a systematic review.
AB  - BACKGROUND: Despite interest in cryopreservation of individual or small number of
      human spermatozoa, to date, little data is available as regards its
      effectiveness. We systematically reviewed the outcome after cryopreservation of
      individual or small numbers of human spermatozoa in patients with severe male
      factor of infertility. METHODS: We searched the MEDLINE, EMBASE, Cochrane
      Systematic Reviews, CENTRAL, Web of Science, Scopus databases for relevant
      studies up to June of 2008. The search used terms referring to cryopreservation
      of small amount of sperm. Included studies were limited to human studies with no
      language restrictions. RESULTS: We identified 30 reports including 9 carriers
      used for cryopreservation of small quantities/numbers of human spermatozoa (7 non
      biological and 2 biological carriers). A wide variety of cryopreservation
      vehicles were reported. The recovery rate of spermatozoa cryopreserved in a known
      small number varied widely from 59 to 100%. Fertilization rates were in the range
      of 18-67%. Frozen-thawed spermatozoa, using this method, were subsequently used
      for intracytoplasmic sperm injection in only five studies, with few pregnancies
      reported so far. To date, there remains no consensus as to the ideal carrier for
      cryopreservation of small number of spermatozoa for clinical purposes.
      CONCLUSIONS: Cryopreservation of individual or small numbers of human spermatozoa
      may replace the need for repeated surgical sperm retrieval. A controlled
      multicenter trial with sufficient follow-up would provide valid evidence of the
      potential benefit of this approach.

PMID- 19109314
TI  - Possible miliary tuberculosis during adalimumab therapy with negative gamma-IFN
      release assays.

PMID- 19109315
TI  - Analgesic effects of treatments for non-specific low back pain: a meta-analysis
      of placebo-controlled randomized trials.
AB  - OBJECTIVE: Estimates of treatment effects reported in placebo-controlled
      randomized trials are less subject to bias than those estimates provided by other
      study designs. The objective of this meta-analysis was to estimate the analgesic
      effects of treatments for non-specific low back pain reported in placebo
      controlled randomized trials. METHODS: Medline, Embase, Cinahl, PsychInfo and
      Cochrane Central Register of Controlled Trials databases were searched for
      eligible trials from earliest records to November 2006. Continuous pain outcomes
      were converted to a common 0-100 scale and pooled using a random effects model.
      RESULTS: A total of 76 trials reporting on 34 treatments were included. Fifty
      percent of the investigated treatments had statistically significant effects, but
      for most the effects were small or moderate: 47% had point estimates of effects
      of <10 points on the 100-point scale, 38% had point estimates from 10 to 20
      points and 15% had point estimates of >20 points. Treatments reported to have
      large effects (>20 points) had been investigated only in a single trial.
      CONCLUSIONS: This meta-analysis revealed that the analgesic effects of many
      treatments for non-specific low back pain are small and that they do not differ
      in populations with acute or chronic symptoms.

PMID- 19109316
TI  - Very low prevalence of anti-CCP antibodies in rheumatoid factor-negative
      psoriatic polyarthritis.

PMID- 19109317
TI  - Risk factors for severe cranial ischaemic events in an Italian population-based
      cohort of patients with giant cell arteritis.
AB  - OBJECTIVE: To evaluate the impact of traditional cardiovascular risk factors,
      carotid atherosclerosis and the effect of anti-platelet/anti-coagulant therapy on
      the occurrence of severe cranial ischaemic events (CIEs) in GCA. METHODS: We
      identified 180 Reggio Emilia (Italy) residents with biopsy-proven GCA diagnosed
      between 1986 and 2005. We evaluated data on demographics, clinical features,
      laboratory investigations, cardiovascular risk factors, anti-platelet/anti
      coagulant use and carotid atherosclerosis. RESULTS: Systemic signs/symptoms were
      significantly less frequent (P = 0.004) and ESR and C-reactive protein (CRP)
      values at diagnosis were significantly lower (P = 0.03 and P = 0.04,
      respectively) in patients with CIEs. The prevalence of hypertension and ischaemic
      heart disease was significantly higher in patients with CIEs than in those
      without (P = 0.01 and P = 0.006, respectively). Patients treated with anti
      platelet/anti-coagulant therapy were significantly more likely to suffer CIEs
      than those without (P = 0.03), while CIEs were significantly associated with
      ischaemic heart disease in this subset of patients (P = 0.02). By multivariate
      logistic regression, we found that the best predictors for the development of
      severe CIEs included the absence of high (>5.38 mg/dl) CRP levels at diagnosis
      (OR = 0.31, 95% CI 0.08, 1.20), the absence of systemic manifestations (OR =
      0.30, 95% CI 0.08, 1.08), the presence of hypertension (OR = 7.77, 95% CI 0.83,
      72.76), and a past history of ischaemic heart disease (OR = 8.65, 95% CI 0.92,
      80.95). CONCLUSIONS: In GCA, hypertension, a past history of ischaemic heart
      disease and a low inflammatory response are associated with a higher risk of
      developing severe CIEs.

PMID- 19109318
TI  - Pregnancy outcome in systemic lupus erythematosus complicated by anti
      phospholipid antibodies.
AB  - OBJECTIVE: Pregnant women affected by SLE are at high risk of gestational
      hypertension and pre-eclampsia (32-50%). This risk is particularly elevated if
      aPLs are dosable. The present study was planned to evaluate maternal-fetal
      outcomes of different groups of SLE pregnant patients characterized by diverse
      risk factors: patients affected by APS treated with a combination of low-dose
      aspirin (LDA) and low-molecular weight heparin (LMWH), nulliparous patients with
      dosable aPL treated by LMWH and SLE patients with no aPL administered no
      treatment during pregnancy. METHODS: A retrospective description of maternal and
      fetal outcomes was made in a total of 62 pregnancies presenting APS in 8 cases
      (12.9%), aPL in 20 (32.2%) and no aPL in 34 (54.8%). RESULTS: No statistically
      significant difference was found comparing fetal and maternal outcomes of the
      three groups despite differences in SLE activity: SLE aPL-positive pregnancies
      were associated with a higher incidence of nephritis and chronic hypertension
      than pregnancies treated for APS or not presenting with the added risk factor.
      The incidence of pre-eclampsia is 15% in aPL positive, 12.5% in APS and 14.7% in
      no aPL pregnancies, respectively. CONCLUSIONS: LMWH is rather a possible option
      of prophylaxis for SLE aPL-positive pregnancies with potential maternal-fetal
      outcomes similar to aPL-negative patients or to standard treated APS.

PMID- 19109320
TI  - Crystal ball gazing: new therapeutic targets for hyperuricaemia and gout.
AB  - Recent studies in diverse disciplines have led to significant advances in the
      understanding of the basic biology of hyperuricaemia and gout, with important
      implications for future treatment. These findings include genetic variation
      within SLC2A9 as a key regulator of urate homeostasis, and identification of
      urate-anion exchanger urate transporter 1 (URAT1) and other renal uric acid
      transporters. Recognition of urate as an endogenous danger signal and activator
      of the adaptive immune response suggests an important role for urate crystals in
      non-microbial immune surveillance. The central role of NALP3 inflammasome
      activation and IL-1beta signalling in the initiation of the acute gout attack
      raises the possibility of new therapeutic targets. Disordered osteoclastogenesis
      in patients with chronic gout highlights potential therapies for prevention of
      joint damage. This review summarizes these findings and the potential relevance
      for future management of gout.

PMID- 19109322
TI  - Commentary: The balance between marketing and safety.

PMID- 19109323
TI  - New definition of myocardial infarction.

PMID- 19109324
TI  - Exercise ECGs in angina. Cost effective investigation of suspected angina.

PMID- 19109325
TI  - Sensitivity and specificity of exercise ECG in heart disease.

PMID- 19109326
TI  - Exercise ECGs in angina. Which "angiographic positives" will die from heart
      disease?

PMID- 19109327
TI  - BCG vaccination in children. Universal BCG in the UK again?

PMID- 19109328
TI  - Routines in collaborative work. Clinical routines in practice.

PMID- 19109329
TI  - Wii seems safe with pacemakers.

PMID- 19109331
TI  - Screening for bowel cancer is set to save 2500 lives a year in UK.

PMID- 19109330
TI  - Morphine remains gold standard in breakthrough cancer pain.

PMID- 19109332
TI  - Memory clinics could improve dementia care, say experts.

PMID- 19109333
TI  - Exposure of the mouse perinatal testis to radiation leads to hypospermia at
      sexual maturity.
AB  - The first round of mouse spermatogenesis begins from 3 to 4 days after birth
      through differentiation of gonocytes into spermatogonial-stem cells and type A
      spermatogonia. Consequently, this step of differentiation may determine
      generation of the original population of stem cells and the fertility potential
      of the adult mouse. We aimed to determine the effect of perinatal exposure to
      ionizing radiation on the testis at the end of the first wave of spermatogenesis
      and at sexual maturity. Our results show that, radiation sensitivity of the
      testis substantially decreases from late foetal life to the end of the first week
      after birth. In addition, partial or full recovery from radiation induced
      testicular weight loss occurred between the first round of spermatogenesis and
      sexual maturity, and this was associated with the stimulation of spermatogonial
      proliferation. Exposure of mice at 17.5 days after conception or at 1 day after
      birth to gamma-rays decreased the sperm counts at sexual maturity, while exposure
      of 8 day-old mice had no effect. This suggests that irradiation of late foetal or
      early neonatal testes has a direct impact on the generation of the neonatal
      spermatogonial-stem cell pool.

PMID- 19109334
TI  - A patient outreach program between visits improves diabetes care: a pilot study.
AB  - OBJECTIVE: Barriers to guideline-based diabetes care include poor patient
      activation, haphazard clinic appointments, poorly organized medical records and a
      lack of automated physician decision support. We developed a patient recall
      intervention to mitigate these barriers and improve diabetes care coordination.
      We evaluated this intervention in terms of operational feasibility, provider and
      patient acceptance and effects on process of care measures. METHODS: On the basis
      of the American Diabetes Association criteria, we identified patients with
      diabetes in a large internal medicine practice who were due for provider visits;
      hemoglobin A1c, lipid, microalbumin and serum creatinine laboratories; and
      retinal examinations. An outreach coordinator contacted patients to summarize
      this information and schedule recommended services. We assessed patient
      responsiveness to outreach and used medical chart review to compare diabetes care
      rendered before and after the intervention. Providers gave feedback about their
      satisfaction with the program. RESULTS: Over 3 months, 709 patients were overdue
      for diabetes-related services. Of 415 overdue for provider visits, a total of 125
      (30.1%) completed such visits arranged by an outreach coordinator and, of these,
      101 (80.8%) completed laboratories at least a day ahead of time. An additional 52
      out of 415 patients (12.5%) bypassed the outreach coordinator to self-schedule
      diabetes visits within a 6-week period after the outreach letter was mailed.
      Among overdue patients, completion of recommended services and intensity of
      diabetes care were significantly greater through the outreach program compared
      with traditional care. Provider attitudes were favorable. CONCLUSIONS: An
      outreach intervention was associated with improved timeliness and intensity of
      diabetes care in an outpatient setting. The success of this pilot program in
      terms of process measures warrants additional evaluation focused on clinical
      outcomes.

PMID- 19109335
TI  - Comparative pharmacodynamic interaction analysis between ciprofloxacin,
      moxifloxacin and levofloxacin and antifungal agents against Candida albicans and
      Aspergillus fumigatus.
AB  - OBJECTIVES: Patients suffering from invasive mycoses often receive concomitant
      antifungal therapy and antibacterial agents. Ciprofloxacin, a
      carboxyfluoroquinolone, was previously observed to demonstrate the
      pharmacodynamic interactions with antifungal agents by altering their growth
      inhibitory activity against Candida albicans and Aspergillus fumigatus. However,
      little is known about the interaction between other extended-spectrum
      fluoroquinolones, such as levofloxacin and moxifloxacin, and antifungal agents
      against C. albicans and A. fumigatus. METHODS: Using a microdilution chequerboard
      technique, we employed isobolographic analysis adapted to incorporate a non
      active agent in order to analyse the potential in vitro interaction between
      ciprofloxacin, levofloxacin or moxifloxacin and the following representative
      antifungal agents: amphotericin B, fluconazole or voriconazole and caspofungin.
      RESULTS: Synergistic interactions [interaction indices (Iis) 0.69-0.83, P < 0.05]
      were observed between amphotericin B (0.07-0.31 mg/L) and either ciprofloxacin
      (0.19-7.65 mg/L) or levofloxacin (0.41-32.88 mg/L) against C. albicans and A.
      fumigatus. Synergy (Iis 0.56-0.87, P < 0.05) also was found between voriconazole
      (0.09-0.14 mg/L) and ciprofloxacin (0.22-11.41 mg/L) as well as between
      caspofungin (8.94-22.07 mg/L) and levofloxacin (0.14-5.17 mg/L) against A.
      fumigatus. Some antagonistic (Iis 1.16-1.29, P < 0.05) interactions were observed
      between fluoroquinolones and fluconazole against C. albicans. In general,
      ciprofloxacin enhanced the activity of antifungal agents more than moxifloxacin
      and levofloxacin against both C. albicans and A. fumigatus. CONCLUSIONS: The
      knowledge of the pharmacodynamic interactions between fluoroquinolones and
      antifungal agents may guide selection and potentially improve the outcome of
      immunosuppressed patients with concurrent bacterial and fungal infections.

PMID- 19109336
TI  - Pharmacokinetics of linezolid in human non-inflamed vitreous after systemic
      administration.
AB  - OBJECTIVES: To determine the concentration-time curves of linezolid in serum and
      vitreous from 24 patients undergoing vitrectomy. METHODS: Vitrectomy was
      performed 1, 2, 4, 8 and 12 h after infusion of 600 mg of linezolid in 20
      patients divided into groups of four. Four additional patients were studied 12 h
      after two separate oral doses of 600 mg of linezolid. Serum samples were obtained
      1 h after linezolid administration to determine C(max); vitreous and a second
      serum sample were taken simultaneously during the vitrectomy in all patients, and
      the concentrations of linezolid in vitreous (C(v)) and serum (C(s)) were
      determined. RESULTS: Among patients who received one intravenous dose of 600 mg
      of linezolid, the highest mean C(v) was observed at 4 and 8 h following linezolid
      administration (3.4 and 3.7 mg/L). The highest mean C(v) was observed in patients
      who received two oral doses of 600 mg of linezolid separated by 12 h (4.5 mg/L),
      which was higher than the MIC(90) for Staphylococcus epidermidis. The highest
      C(v)/C(s) ratio was reached 12 h after administration of one and two doses (2.4
      and 1.5, respectively). CONCLUSIONS: Microbiologically significant concentrations
      of linezolid can be achieved in the vitreous of the non-inflamed human eye after
      intravenous administration of 600 mg, and it is even better after two doses of
      600 mg. It appears that linezolid accumulates in the vitreous, achieving
      potentially useful steady-state concentrations. An evaluation of clinical
      efficacy is needed to confirm the perceived utility based on the
      pharmacokinetics.

PMID- 19109337
TI  - An econometric view of the dynamic relationship between antibiotic consumption,
      hand disinfection and methicillin-resistant Staphylococcus aureus.

PMID- 19109338
TI  - Impact of biofilm on the in vitro activity of vancomycin alone and in combination
      with tigecycline and rifampicin against Staphylococcus aureus.
AB  - OBJECTIVES: This study evaluated vancomycin susceptibility and activity alone and
      in combination with rifampicin and tigecycline against low-biofilm- and high
      biofilm-producing methicillin-resistant Staphylococcus aureus (MRSA) clinical
      isolates. METHODS: Forty MRSA isolates recovered from bloodstream infections were
      analysed. Susceptibilities were performed in planktonic and biofilm cultures by
      microbroth dilution. Biofilm production was determined using an adherent plate
      assay. Time-kill analysis was performed on six low- and six high-biofilm
      producing isolates with 15 mg/L vancomycin alone and in combination with
      rifampicin or tigecycline at 4x MIC. RESULTS: Vancomycin susceptibility displayed
      a 4-fold and an 8-fold increase in the MIC(50) and MIC(90), respectively, in the
      presence of biofilm. Rifampicin and tigecycline susceptibilities also increased
      in biofilms, but still remained within the susceptibility breakpoints except for
      a tigecycline MIC(90) of 1 mg/L. High biofilm production was detected in 60% of
      the isolates. In time-kill analysis, 15 mg/L vancomycin achieved bactericidal
      activity against only low-biofilm-producing strains with a 1.8 log(10) cfu/mL
      difference in bacterial kill compared with high-biofilm-producing strains (P <
      0.001). Rifampicin alone had minimal activity, resulting in resistance.
      Tigecycline was minimally effective and was not bactericidal, but no difference
      was observed in the comparison of biofilm-producing strains. Vancomycin in
      combination with rifampicin or tigecycline was bactericidal against all strains
      (mean kill 4.5 +/- 0.5 log(10) cfu/mL), regardless of biofilm production.
      CONCLUSIONS: Vancomycin exposures at 15 mg/L may not be adequate in eradicating
      biofilm-producing S. aureus. Alternative treatments or combination therapy should
      be explored to optimize outcomes in biofilm-associated infections.

PMID- 19109339
TI  - Morphological features and signature gene response elicited by inactivation of
      FtsI in Mycobacterium tuberculosis.
AB  - OBJECTIVES: Universally conserved events in cell division provide the opportunity
      for the development of novel chemotherapeutics against Mycobacterium
      tuberculosis. The aim of this study was to use the beta-lactam antimicrobials
      cefalexin and piperacillin to inhibit FtsI and characterize the morphological
      changes and global transcriptional activities of genes to identify a signature
      response to FtsI inactivation. METHODS: Cefalexin and piperacillin were used to
      block cell division, and microscopy was used to evaluate the effects on bacterial
      morphology and ultrastructure. Global transcriptional analysis was performed to
      determine the impact of FtsI inhibition on cell cycle processes and to identify
      molecular markers. RESULTS: Inhibition of FtsI with cefalexin and piperacillin
      resulted in filamentous cells with multiple concentric rings and occasional
      branching as visualized by light and electron microscopy. Whole genome microarray
      based transcriptional profiling and transcriptional mapping allowed the
      evaluation of cell cycle processes in response to inhibition of FtsI and
      characterization of transcriptional response and cell cycle processes.
      CONCLUSIONS: This study substantiated that FtsZ-ring constriction and septal
      resolution require the transpeptidase activity of FtsI, making FtsI essential for
      cell division in M. tuberculosis. Therefore, FtsI is a target for drug discovery,
      and these studies provided a molecular signature of FtsI inactivation that can be
      applied to screening strategies for novel FtsI inhibitors.

PMID- 19109340
TI  - Leakage into Portuguese aquatic environments of extended-spectrum-beta-lactamase
      producing Enterobacteriaceae.

PMID- 19109341
TI  - The place for harm reduction and product regulation in UK tobacco control policy.
AB  - Tobacco use remains the leading cause of preventable death in this country and
      more needs to be done to reduce smoking rates. Harm reduction is one policy
      option. Smokers smoke for the nicotine, but die from the other toxins in
      cigarette smoke. Harm reduction in tobacco control aims to reduce the harm
      arising from nicotine use by shifting smokers, who are unable to quit, to using
      far less hazardous sources of nicotine, notably medicinal nicotine, in place of
      cigarettes. This article argues that for harm reduction to work in the UK, a
      nicotine product regulation authority is first needed. This would regulate
      nicotine products in proportion to harm to ensure that, contrary to the current
      paradoxical arrangements, the most harmful source of nicotine, the cigarette,
      becomes the most highly regulated (and thus the least easily accessible,
      available and attractive). It goes onto explore how a harm reduction strategy
      might be further developed, exploring controversies and potential pitfalls. It
      argues that the public health community needs to own and drive this debate
      because failure to do so would let the tobacco industry gain the upper hand and
      see thousands of more unnecessary deaths from tobacco use.

PMID- 19109342
TI  - Harm reduction in tobacco control.

PMID- 19109343
TI  - Where now for tobacco control--no place yet for harm reduction in tobacco
      control.

PMID- 19109344
TI  - Where now for tobacco control--the place for harm reduction and product
      regulation in UK tobacco control policy: a perspective from India.

PMID- 19109347
TI  - Atrial fibrillation in acute myocardial infarction: a systematic review of the
      incidence, clinical features and prognostic implications.
AB  - Atrial fibrillation (AF), the most commonly encountered clinical arrhythmia,
      often complicates acute myocardial infarction (AMI) with an incidence between 6
      and 21%. Predictors of the arrhythmia in the setting of AMI include advanced age,
      heart failure symptoms, and depressed left ventricular function. The bulk of
      evidence demonstrates that AF in patients hospitalized for AMI has serious
      adverse prognostic implications regarding in-hospital, but also long-term
      mortality. This seems to apply for all patient populations studied without
      significant differences related to the treatment of AMI (i.e. no reperfusion
      therapy vs. thrombolysis vs. percutaneous coronary intervention). Mortality is
      particularly high in patients who have congestive heart failure and/or a reduced
      left ventricular ejection fraction. Finally, there are persuasive data indicating
      that AF complicating AMI not only increases the risk for ischaemic stroke during
      hospitalization but also during follow-up. This seems to apply also for transient
      AF which has reversed back to sinus rhythm at the time of discharge. These
      observations emphasize the need for prospective studies evaluating optimal
      therapeutic approaches for patients with AMI complicated by AF.

PMID- 19109348
TI  - The late open artery hypothesis: the case and the artery remain closed.

PMID- 19109349
TI  - Cardiac computed tomography for the diagnosis of right ventricular implantable
      cardioverter-defibrillator lead perforation.

PMID- 19109350
TI  - ESC guidelines for the diagnosis and treatment of acute and chronic heart failure
      2008: application of natriuretic peptides.

PMID- 19109351
TI  - Survival trends in men and women with heart failure of ischaemic and non
      ischaemic origin: data for the period 1987-2003 from the Swedish Hospital
      Discharge Registry.
AB  - AIMS: To investigate gender-specific trends in long-term mortality in patients
      hospitalized for heart failure (HF). METHODS AND RESULTS: The Swedish hospital
      discharge and cause-specific death registers were used to calculate age- and
      gender-specific trends for long-term prognosis in patients hospitalized with a
      principal diagnosis of HF from 1987 to 2003. Mortality decreased, mainly during
      1987-95, with no further decrease after 2001. Survival in men improved more than
      in women (P-value for interaction 0.0003), particularly among patients aged <65
      years (P-value for interaction: age, gender, and year of hospitalization 0.0003)
      and more for patients with ischaemic when compared with non-ischaemic HF (P-value
      for interaction <0.0001). Among men <65 years, the hazard ratio (HR) of dying
      within 3 years after discharge was 0.40 (95% confidence interval 0.36-0.45)
      during 1999-2001 when compared with 1987-89. The corresponding HR for women was
      0.58 (0.48-0.69). For those discharged during 1999-2001, almost 20% of the
      patients aged 35-64 years and 40% of those aged 65-84 years died within 3 years.
      CONCLUSION: Long-term mortality in HF in Sweden decreased more for men than for
      women and more for ischaemic than non-ischaemic HF. There was no further decrease
      after 2001. Long-term mortality after a first hospitalization remained high.

PMID- 19109353
TI  - The 'single big cryoballoon' technique for acute pulmonary vein isolation in
      patients with paroxysmal atrial fibrillation: a prospective observational single
      centre study.
AB  - AIMS: Cryothermal energy (CTE) ablation via a balloon catheter (Arctic Front,
      Cryocath) represents a novel technology for pulmonary vein isolation (PVI).
      However, balloon-based PVI approaches are associated with phrenic nerve palsy
      (PNP). We investigated whether 'single big cryoballoon'-deployed CTE lesions can
      (i) achieve acute electrical PVI without left atrium (LA) imaging and (ii) avoid
      PNP in patients with paroxysmal atrial fibrillation (PAF). METHODS AND RESULTS:
      After double transseptal punctures, one Lasso catheter and a big 28 mm
      cryoballoon catheter using a steerable sheath were inserted into the LA. PV
      angiography and ostial Lasso recordings from all PVs were obtained. Selective PV
      angiography was used to evaluate balloon to LA-PV junction contact. CTE ablation
      lasted 300 s, and the PN was paced during freezing at right-sided PVs. Twenty
      seven patients (19 males, mean age: 56 +/- 9 years, LA size: 42 +/- 5 mm) with
      PAF (mean duration: 6.6 +/- 5.7 years) were included. PVI was achieved in 97/99
      PVs (98%). Median (Q(1); Q(3)) procedural, balloon, and fluoroscopy times were
      220 min (190; 245), 130 min (90; 170), and 50 min (42; 69), respectively. Three
      transient PNP occurred after distal PV ablations. No PV stenosis occurred. Total
      median (Q(1); Q(3)) follow-up time was 271 days (147; 356), and 19 of 27 patients
      (70%) remained in sinus rhythm (3-month blanking period). CONCLUSION: Using the
      single big cryoballoon technique, almost all PVs (98%) could be electrically
      isolated without LA imaging and may reduce the incidence of PNP as long as distal
      ablation inside the septal PVs is avoided.

PMID- 19109354
TI  - Behavioural interventions for smoking cessation: a meta-analysis of randomized
      controlled trials.
AB  - AIMS: Widely varying estimates of treatment effects have been reported in
      randomized controlled trials (RCTs) investigating the efficacy of behavioural
      interventions for smoking cessation. Previous meta-analyses investigating
      behavioural interventions have important limitations and do not include recently
      published RCTs. We undertook a meta-analysis of RCTs to synthesize the treatment
      effects of four behavioural interventions, including minimal clinical
      intervention (brief advice from a healthcare worker), and intensive
      interventions, including individual, group, and telephone counselling. METHODS
      AND RESULTS: We searched the CDC Tobacco Information and Prevention, Cochrane
      Library, EMBASE, Medline, and PsycINFO databases. We included only RCTs that
      reported biochemically validated smoking cessation outcomes at 6 and/or 12 months
      after the target quit date. Outcomes were aggregated using hierarchical Bayesian
      random-effects models. We identified 50 RCTs, which randomized n = 26 927
      patients (minimal clinical intervention: 9 RCTs, n = 6456; individual
      counselling: 23 RCTs, n = 8646; group counselling: 12 RCTs, n = 3600; telephone
      counselling: 10 RCTs, n = 8225). The estimated mean treatment effects were
      minimal clinical intervention [odds ratio (OR) 1.50, 95% credible interval (CrI)
      0.84-2.78], individual counselling (OR 1.49, 95% CrI 1.08-2.07), group
      counselling (OR 1.76, 95% CrI 1.11-2.93), and telephone counselling (OR 1.58, 95%
      CrI 1.15-2.29). CONCLUSION: Intensive behavioural interventions result in
      substantial increases in smoking abstinence compared with control. Although
      minimal clinical intervention may increase smoking abstinence, there is
      insufficient evidence to draw strong conclusions regarding its efficacy.

PMID- 19109355
TI  - Development of life-expectancy tables for people with type 2 diabetes.
AB  - AIMS: To develop tables that report the life expectancy associated with levels of
      major modifiable risk factors for patients with type 2 diabetes. METHODS AND
      RESULTS: A set of tables reporting life-expectancy stratified by age-sex groups
      for combinations of modifiable risk was constructed based on predictions from the
      United Kingdom Prospective Diabetes Study (UKPDS) Outcomes Model. This model is
      based on a system of parametric proportional hazards risk equations for
      estimating mortality and vascular complications of diabetes that have been
      estimated from 3642 patients from the UKPDS. The tables show substantial
      potential gains in life expectancy within every age group from modifying major
      risk factors. The estimated life expectancy of men at age of 55 years with type 2
      diabetes, 5 years after diagnosis, varies between 13.2 years for a patient who
      smokes, has systolic blood pressure of 180 mmHg, a total:HDL cholesterol ratio of
      8, and HbA(1c) of 10%, and 21.1 years for a non-smoker with SBP of 120 mmHg,
      total/HDL ratio of 4, and HbA(1c) of 6%. CONCLUSION: Life expectancy tables
      provide a potentially useful tool of conveying prognostic information to people
      with type 2 diabetes and suggest substantial scope for increasing longevity by
      improving modifiable risk factors.

PMID- 19109356
TI  - Expression of stromal-cell-derived factor-1 on circulating platelets is increased
      in patients with acute coronary syndrome and correlates with the number of CD34+
      progenitor cells.
AB  - AIMS: Previous experimental studies have suggested that platelet stromal-cell
      derived factor-1 (SDF-1) regulates mobilization and recruitment of haematopoietic
      progenitor cells supporting revascularization in mice. However, there are no
      clinical data available regarding platelet-bound SDF-1 in patients with acute
      coronary syndrome (ACS). The objective of this study was to evaluate the platelet
      surface expression of SDF-1 in patients with ACS. METHODS AND RESULTS: Patients
      with ACS (n = 418) showed a significantly enhanced SDF-1 expression on admission
      compared with those with stable angina pectoris (SAP, n = 486) [SAP (mean
      fluorescence intensity (MFI) +/- SD): 13.48 +/- 5.27; ACS: 18.45 +/- 12.85; P <
      0.001) independent of cardiovascular risk factors and medication. Enhanced
      platelet-bound SDF-1 expression was found in patients with reduced left
      ventricular ejection fraction (LVEF <55%) in comparison to patients with normal
      LVEF (P = 0.005). Platelet-bound SDF-1 expression positively correlated with the
      degree of platelet activation [CD62P: r = 0.325; glycoprotein VI (GPVI): r =
      0.277; PAC-1: r = 0.501; P < 0.001 for all] and showed a significant, but slight
      association with plasma levels of SDF-1 (r = 0.084; P = 0.045). In a subgroup of
      patients with coronary artery disease, platelet-bound SDF-1, but not other
      platelet activation markers, significantly correlated with the number of
      circulating CD34(+) progenitor cells (r = 0.252; P = 0.002) or CD34(+)/CD133(+)
      endothelial progenitor cells (r = 0.352; P = 0.008). CONCLUSION: Platelet-bound
      SDF-1 may play an important role in peripheral homing of circulating progenitor
      cells thus in tissue regeneration.

PMID- 19109357
TI  - Facilitatory interplay in alpha 1a and beta 2 adrenoceptor function reveals a non
      Gq signaling mode: implications for diversification of intracellular signal
      transduction.
AB  - Agonist occupied alpha(1)-adrenoceptors (alpha(1)-ARs) engage several signaling
      pathways, including phosphatidylinositol hydrolysis, calcium mobilization,
      arachidonic acid release, mitogen-activated protein (MAP) kinase activation, and
      cAMP accumulation. The natural agonist norepinephrine (NE) activates with
      variable affinity and intrinsic efficacy all adrenoceptors, and in cells that
      coexpress alpha(1)- and beta-AR subtypes, such as cardiomyocytes, this leads to
      coactivation of multiple downstream pathways. This may result in pathway cross
      talk with significant consequences to heart physiology and pathologic state. To
      dissect signaling components involved specifically in alpha(1A)- and beta(2)-AR
      signal interplay, we have developed a recombinant model system that mimics the
      levels of receptor expression observed in native cells. We followed intracellular
      Ca(2+) mobilization to monitor in real time the activation of both G(q) and G(s)
      pathways. We found that coactivation of alpha(1A)- and beta(2)-AR by the
      nonselective agonist NE or via a combination of the highly selective alpha(1A)-AR
      agonist A61603 and the beta-selective agonist isoproterenol led to increases in
      Ca(2+) influx from the extracellular compartment relative to stimulation with
      A61603 alone, with no effect on the associated transient release of Ca(2+) from
      intracellular stores. This effect became more evident upon examination of an
      alpha(1A)-AR variant exhibiting a partial defect in coupling to G(q), and we
      attribute it to potentiation of a non G(q)-pathway, uncovered by application of a
      combination of xestospongin C, an endoplasmic reticulum inositol 1,4,5
      triphosphate receptor blocker, and 2-aminoethoxydiphenyl borate, a nonselective
      storeoperated Ca(2+) entry channel blocker. We also found that stimulation with
      A61603 of a second alpha(1A)-AR variant entirely unable to signal induced no
      Ca(2+) unless beta(2)-AR was concomitantly activated. These results may be
      accounted for by the presence of alpha(1A)/beta(2)-AR heterodimers or
      alternatively by specific adrenoceptor signal cross-talk resulting in distinct
      pharmacological behavior. Finally, our findings provide a new conceptual
      framework to rationalize outcomes from clinical studies targeting alpha- and beta
      adrenoceptors.

PMID- 19109358
TI  - Defibrillator shock due to ventricular trigeminy.
AB  - A 56-year-old lady with arrhythmogenic right ventricular cardiomyopathy had a
      shock for ventricular trigeminy. The device diagnosed this as ventricular
      fibrillation because of its binning algorithm, which does not use a consecutive,
      or a proportional counter. A beat is binned as a fibrillation beat only if the
      current cycle length is in the fibrillation zone and the running average of the
      previous four cycle lengths are in the fibrillation or ventricular tachycardia
      zone. Reprogramming the device into a single detection zone will help prevent
      shocks in this situation.

PMID- 19109359
TI  - Subacute cardiac perforations associated with active fixation leads.
AB  - AIMS: Having several recently published reports on increased rate of cardiac
      perforation with some lead models as background, we assess the relation between
      cardiac perforations and models of leads used. METHODS AND RESULTS: All pacing
      and defibrillation leads implantations between 1 January 2007 and 31 March 2008
      were analysed retrospectively. There were 2247 leads implanted in 1419 patients
      aged 67.6 +/- 14.1, 1200 (53%) active and 1047 (47%) passive fixation leads.
      Cardiac perforation occurred in eight patients (0.5%). The number of perforations
      does not differ significantly between the pacemaker and implantable cardioverter
      defibrillator implantations (five and three cases, respectively, P = 0.13). All
      perforations were associated with the active fixation leads implantation (8 vs.
      0, P < 0.01). Only four models of leads were associated with perforations, but
      the risk of their use was not statistically significantly increased, when
      compared with other active fixation leads placed in the adequate position.
      CONCLUSIONS: The incidence of cardiac perforation related to pacing and
      defibrillation leads is low. The use of active fixation leads is associated with
      an increased risk of cardiac perforation. We did not find any correlation between
      the perforation rate and any particular model of the implanted lead.

PMID- 19109360
TI  - Percutaneous catheter ablation of atrial fibrillation in a patient with an
      anomalous pulmonary venous connection.

PMID- 19109361
TI  - Routine echocardiography after radiofrequency ablation: to flog a dead horse?
AB  - AIMS: Radiofrequency ablation (RFA) is frequently used to treat sustained
      arrhythmias. One major complication is pericardial effusion-tamponade. Therefore,
      many centres perform echocardiography after interventions, but data on necessity
      of such routine procedures are scarce. METHODS AND RESULTS: We included 510
      patients with RFA and compared echocardiographic results acquired before and <24
      h after intervention. We defined pericardial effusion as 'small', if <10 mm in
      diastole, 'moderate' if >10 mm, 'large' if >20 mm, or tamponade (>20 mm with
      haemodynamic compromise). Age was 55 +/- 16 years, 40% were females. Thirty-five
      percentage underwent RFA for atrioventricular nodal re-entrant tachycardia
      (AVNRT), 28% for atrial flutter, 15% for atrial fibrillation (AF), 12% for Wolff
      Parkinson-White (WPW) syndrome, and 10% for different other arrhythmias. In 16
      patients (3.2%), small asymptomatic effusions were detected. The only moderate
      effusion was suspected due to procedure circumstances. Radiofrequency ablation
      for AF had a higher incidence compared to AVNRT and flutter (P = 0.001 and
      <0.0001, respectively) or to WPW syndrome (P = 0.06). CONCLUSION: Numbers of
      significant pericardial effusion as detected by routine echocardiography were low
      (3.6%) and clinically relevant effusions absent. We thus recommend performing
      echocardiography after RFA only, if effusion is suspected clinically or if RFA
      was performed for AF, due to the high incidence of effusions with this type of
      ablation.

PMID- 19109362
TI  - Leads and longevity: how long will your pacemaker last?

PMID- 19109363
TI  - Spectral analysis of intracardiac electrograms during induced and spontaneous
      ventricular fibrillation in humans.
AB  - AIMS: Very limited data are available on the differences between spontaneous and
      induced episodes of ventricular fibrillation (VF) in humans. The aim of the study
      was to compare the spectral characteristics of the electrical signal recorded by
      an implantable cardioverter defibrillator (ICD) during both types of episodes.
      METHODS AND RESULTS: Thirteen ICD patients with at least one spontaneous and one
      induced VF recorded by the device were included in the study. A spectral
      representation was obtained for the first 3 s of the intracardiac unipolar
      electrogram during VF. The dominant frequency (f(d)), the peak power at f(d), an
      organization index (OI), a bandwidth measurement, and an estimate of the
      correlation with a sinusoidal wave (leakage) were estimated for each episode. The
      f(d) was higher in induced episodes (4.75 +/- 0.57 vs. 3.95 +/- 0.59 Hz for the
      spontaneous episodes, P = 0.002), as well as the degree of organization assessed
      by the OI, bandwidth, and leakage parameters. CONCLUSION: Clinical and induced VF
      episodes in humans have different spectral characteristics. Changes in the
      electrophysiological substrate or in the location of the arrhythmia wavefront at
      onset could play a role to explain the observed differences.

PMID- 19109364
TI  - Vasopressin: more than just an output of the circadian pacemaker? Focus on
      "Vasopressin receptor V1a regulates circadian rhythms of locomotor activity and
      expression of clock-controlled genes in the suprachiasmatic nuclei".

PMID- 19109365
TI  - Mast cells are necessary for the hypothermic response to LPS-induced sepsis.
AB  - As central nervous system residents, mast cells contain many cytokines and are
      localized primarily near large blood vessels in the diencephalon and within the
      leptomeninges, making them candidates for immune to neural "cross talk." Using
      mast cell-deficient Kit(W-sh/W-sh) mice, we assessed the role of these cells in
      the thermoregulatory component of the immune response to lipopolysaccharide
      (LPS). Kit(W-sh/W-sh) and wild-type (WT) mice differed in several respects in
      response to injection of a high dose of LPS (1 mg/kg ip). Core temperature (T(c))
      of WT mice decreased by approximately 3 degrees C, whereas Kit(W-sh/W-sh) mice
      did not become hypothermic but instead exhibited pronounced low-frequency T(c)
      oscillations around their baseline temperature. In addition, Kit(W-sh/W-sh) mice
      had lower levels of whole brain TNF-alpha but no differences in IL-1beta, IL-6,
      IFN-gamma, or histamine compared with WT mice following injection of the high
      dose of LPS, consistent with the role of TNF-alpha in sepsis. Kit(W-sh/W-sh) mice
      had increased resistance to LPS, and some survived a dose of LPS that was lethal
      in littermate controls. In contrast, Kit(W-sh/W-sh) and WT mice were similar in
      other aspects, namely, in the hyperthermia following injection of TNF-alpha (1.5
      microg icv), reduced nighttime T(c) and locomotor activity (to 1 mg/kg LPS),
      response to a low dose of LPS (10 microg/kg ip), and response to subcutaneous
      turpentine injection. These results indicate that mast cells play a role in the
      regulation of thermoregulatory responses and survival following sepsis induction
      and suggest a brain site of action.

PMID- 19109366
TI  - High-salt diet enhances mouse aortic relaxation through adenosine A2A receptor
      via CYP epoxygenases.
AB  - We hypothesize that A(2A) adenosine receptors (A(2A) AR) promote aortic
      relaxation in mice through cytochrome P450 (CYP)-epoxygenases and help to avoid
      salt sensitivity. Aortas from male mice maintained on a high-salt (HS; 7% NaCl)
      or normal-salt (NS; 0.45% NaCl) diet for 4-5 wks were used. Concentration
      response curves (10(-11)-10(-5) M) for 5'-N-ethylcarboxamidoadenosine (NECA; a
      nonselective adenosine analog) and CGS 21680 (A(2A) AR agonist) were obtained
      with different antagonists including ZM 241385 (A(2A) AR antagonist; 10(-6) M),
      SCH 58261 (A(2A) AR antagonist; 10(-6) M), N(omega)-nitro-l-arginine methyl ester
      (l-NAME; endothelial nitric oxide synthase inhibitor; 10(-4) M) and inhibitors
      including methylsulfonyl-propargyloxyphenylhexanamide (MS-PPOH; CYP epoxygenases
      inhibitor; 10(-5)M), 14,15-epoxyeicosa-5(z)-enoic acid (14,15-EEZE; EET
      antagonist; 10(-5)M), dibromo-dodecenyl-methylsulfimide (DDMS; CYP4A inhibitor;
      10(-5)M), and HET0016 (20-HETE inhibitor; 10(-5)M). At 10(-7) M of NECA,
      significant relaxation in HS (+22.58 +/- 3.12%) was observed compared with
      contraction in NS (-10.62 +/- 6.27%, P < 0.05). ZM 241385 changed the NECA
      response to contraction (P < 0.05) in HS. At 10(-7) M of CGS 21680, significant
      relaxation in HS (+32.04 +/- 3.08%) was observed compared with NS (+10.45 +/-
      1.34%, P < 0.05). SCH 58261, l-NAME, MS-PPOH, and 14,15-EEZE changed the CGS
      21680-induced relaxation to contraction (P < 0.05) in HS. Interestingly, DDMS and
      HET0016 changed CGS 21680 response to relaxation (P < 0.05) in NS; however, there
      was no significant difference found between DDMS, HET0016-treated HS and NS vs.
      nontreated HS group (P > 0.05). CYP2C29 protein was 55% and 74% upregulated in HS
      vs. NS (P < 0.05) mice aorta and kidney, respectively. CYP4A protein was 30.30%
      and 35.70% upregulated in NS vs. HS (P < 0.05) mice aorta and kidneys,
      respectively. A(1) AR was downregulated, whereas A(2A) AR was upregulated in HS
      compared with NS. These data suggest that HS may activate CYP2C29 via A(2A) AR,
      causing relaxation, whereas NS may contribute to the upregulation of CYP4A
      causing contraction.

PMID- 19109367
TI  - Anterograde transneuronal viral tract tracing reveals central sensory circuits
      from white adipose tissue.
AB  - The origins of the sympathetic nervous system (SNS) innervation of white adipose
      tissue (WAT) have been defined using the transneuronal viral retrograde tract
      tracer, pseudorabies virus. Activation of this SNS innervation is acknowledged as
      the principal initiator of WAT lipolysis. The central control of WAT lipolysis
      may require neural feedback to a brain-SNS-WAT circuit via WAT afferents. Indeed,
      conventional tract tracing studies have demonstrated that peripheral
      pseudounipolar dorsal root ganglion (DRG) sensory cells innervate WAT. The
      central nervous system projections of WAT afferents remain uncharted, however,
      and form the focus of the present study. We used the H129 strain of the herpes
      simplex virus-1 (HSV-1), an anterograde transneuronal viral tract tracer, to
      define the afferent circuits projecting from WAT to the central nervous system.
      Siberian hamster inguinal (IWAT) or epididymal WAT was injected with H129 and the
      neuraxis processed for HSV-1 immunoreactivity. We found substantial overlap in
      the pattern of WAT sensory afferent projections with multiple SNS outflow sites
      along the neuraxis, suggesting the possibility of WAT sensory-SNS circuits that
      could regulate WAT SNS drive and thereby lipolysis. Previously, we demonstrated
      that systemic 2-deoxy-d-glucose (2DG) elicited increases in the SNS drive to
      IWAT. Here, we show that systemic 2DG administration also significantly increases
      multiunit spike activity arising from decentralized IWAT afferents. Collectively,
      these data provide structural and functional support for the existence of a
      sensory WAT pathway to the brain, important in the negative feedback control of
      lipid mobilization.

PMID- 19109368
TI  - Is baroreflex control of sympathetic activity and heart rate active in the
      preterm fetal sheep?
AB  - The arterial baroreflex is a fundamental reflex that buffers rapid changes in
      arterial blood pressure (BP) via regulation of the heart rate and sympathetic
      nerve activity to the vasculature. In adults a sigmoidal relationship between BP
      and both heart rate and sympathetic nerve activity is well documented. Its role
      in blood pressure control before birth is unclear. Preterm babies have a high
      incidence of low BP, especially in the first few days of life, which could be
      related, in part, to immaturity of the baroreflex. In the present study, we
      investigated the baroreflex control of fetal heart rate and renal sympathetic
      nerve activity (RSNA) in preterm fetal sheep in utero (102 +/- 1 days of
      gestation; term 140 days). Phenylephrine was associated with a significant
      increase in BP from 38 +/- 2 to 58 +/- 3 mmHg and a decrease in heart rate (HR)
      from 177 +/- 4 to 116 +/- 8 beats per minute (bpm). Sodium nitroprusside was
      associated with a significant fall in BP from 38 +/- 2 to 26 +/- 1 mmHg and an
      increase in HR from 182 +/- 4 to 274 +/- 8 bpm. However, the time between the 50%
      changes in BP and HR was significantly greater after hypotension than
      hypertension (31 +/- 8 s vs. 14 +/- 5 s, P < 0.05). No significant changes in
      RSNA occurred with either stimulus. This suggests that there are different
      maturational tempos for the components of the central autonomic response to
      altered blood pressure.

PMID- 19109369
TI  - Forebrain melanocortin signaling enhances the hindbrain satiety response to CCK
      8.
AB  - Melanocortin 4 receptors (MC4R) are hypothesized to mediate the central nervous
      system actions of leptin to enhance the satiety effects of cholecystokinin (CCK).
      To further elucidate this mechanism, we confirmed that peripheral administration
      of CCK-8 is less effective in producing this effect in MC4R-deficient mice (MC4R(
      /-)). Whereas intraperitoneal (ip) CCK-8 at 0.75 nmol/kg lean body mass (lbm)
      suppressed food intake in wild-type mice, CCK-8 doses of 7.5 nmol/kg lbm were
      required to attenuate food intake in MC4R(-/-) mice. To determine whether
      melanocortin signaling in the hypothalamic paraventricular nucleus (PVN)
      participates in regulating this CCK satiety response, we administered the
      MC3/MC4R antagonist, SHU9119, into the PVN of rats before ip CCK-8
      administration. PVN administration of SHU9119 attenuated the ability of CCK-8 to
      reduce 30-min food intake by 20%. To determine whether MC4R are expressed by PVN
      neurons that project directly to hindbrain nuclei involved in the satiety
      response to ip CCK-8, the retrograde tracer fluorescent cholera toxin subunit B
      was injected into the nucleus tractus solitarius (NTS) of the hindbrain. After 4
      days, labeled PVN neurons were collected by laser capture microdissection and
      found to express MC4R mRNA by quantitative RT-PCR analysis. These data provide
      evidence for a neuroanatomical link between hypothalamic melanocortin signaling
      in the PVN and NTS neurons that regulate food intake. These findings highlight
      the contribution of melanocortin signaling in the PVN toward regulating the
      satiety effects of CCK-8 while acknowledging that melanocortin-dependent pathways
      in other brain regions and/or melanocortin-independent mechanisms are also
      important in this mechanism.

PMID- 19109370
TI  - Reactive oxygen species-dependent endothelin signaling is required for augmented
      hypoxic sensory response of the neonatal carotid body by intermittent hypoxia.
AB  - We previously reported that intermittent hypoxia (IH) augments hypoxic sensory
      response (HSR) and increases the number of glomus cells in neonatal carotid
      bodies. In the present study, we tested the hypothesis that recruitment of
      endothelin-1 (ET-1) signaling by reactive oxygen species (ROS) plays a critical
      role in IH-evoked changes in neonatal carotid bodies. Experiments were performed
      on neonatal rats exposed either to 10 days of IH (P0-P10; 8 h/day) or to
      normoxia. IH augmented HSR of the carotid bodies ex vivo and resulted in
      hyperplasia of glomus cells. The effects of IH were associated with enhanced
      basal release of ET-1 under normoxia, sensitization of carotid body response to
      exogenous ET-1, and upregulation of ET(A) but not an ET(B) receptor mRNA without
      altering the ET-1 content. An ET(A) but not ET(B) receptor antagonist prevented
      augmented HSR by IH. ROS levels were elevated in carotid bodies from IH-treated
      rat pups as evidenced by increased levels of malondialdehyde. Systemic
      administration of manganese (III) tetrakis(1-methyl-4-pyridyl)porphyrin
      pentachloride (MnTMPyP; 5 mg/kg ip), a scavenger of O(2)(*-), prevented IH
      induced elevation of ROS, basal release of ET-1, upregulation of ET(A) mRNA, and
      augmented HSR. In striking contrast, MnTMPyP treatment had no significant effect
      on IH-induced hyperplasia of glomus cells. These results demonstrate that IH
      evoked increase in HSR involve a ROS-mediated increase in basal ET-1 release and
      upregulation of ET(A) receptor mRNA.

PMID- 19109371
TI  - Nonlinear properties of vagal and sympathetic modulations of heart rate
      variability in ovine fetus near term.
AB  - Fetal heart rate (FHR) monitoring is commonly used although clinical studies
      questioned its diagnostic value. Sophisticated FHR variability (fHRV) measures
      such as fHRV complexity may improve the sensitivity and specificity of FHR
      monitoring. A more detailed understanding of the physiology underlying fHRV
      complexity is essential to harness its use for monitoring fetal health. To
      examine the specific effects of vagal and sympathetic modulations on fHRV
      complexity, we blocked vagal activity with atropine and sympathetic activity with
      propranolol in near-term fetal sheep (n = 7, 0.85 gestation). Under these
      conditions, we analyzed the linear and nonlinear parts of fHRV complexity from
      autonomic information flow. Overall fHRV complexity decreased with both drugs
      compared with nonrapid eye movement sleep baseline (P < 0.05). With atropine,
      this was because of a decrease of the linear part of fHRV complexity on the long
      term time scale (P < 0.05), suggesting that vagal modulation of fHRV is
      adequately described by linear fHRV measures. With propranolol, the nonlinear
      part of fHRV complexity decreased on the short-term time scale (P < 0.05),
      suggesting that sympathetic influences on fHRV can be detected by the nonlinear
      part of fHRV complexity. Thus the complex interplay of vagal and sympathetic
      modulations of fHRV is reflected differently and specifically in the linear and
      nonlinear properties of fHRV complexity, and on different time scales. Analysis
      of linear and nonlinear properties of fHRV may improve sensitivity and
      specificity of FHR monitoring.

PMID- 19109372
TI  - Osmosensitivity of prolactin cells is enhanced by the water channel aquaporin-3
      in a euryhaline Mozambique tilapia (Oreochromis mossambicus).
AB  - In teleost fish, prolactin (PRL) has important actions in the regulation of salt
      and water balances in freshwater (FW) fish. Consistent with this role, the
      release of PRL from the pituitary of the Mozambique tilapia is stimulated as
      extracellular osmolality is reduced. Stretch-activated calcium-permeant ion
      channels appear to be responsible for the initiation of the signal transduction
      that leads to increased PRL release when PRL cells are exposed to reductions in
      extracellular osmolality. In this study, we examined a possible involvement of
      the aquaporin-3 (AQP3) water channel in this osmoreceptive mechanism in PRL cells
      of the tilapia. AQP3 expression levels in the rostral pars distalis of the
      pituitary, consisting predominantly of PRL cells, were higher in fish adapted to
      FW than in seawater (SW)-adapted fish. Immunohistochemical studies revealed that
      AQP3 is located in the cell membrane and perinuclear region of PRL cells, with
      more intense immunosignals in PRL cells of FW-adapted fish than in those of SW
      fish. In FW PRL cells, the magnitude of hyposmoticity-induced cell volume
      increase was greater than that seen in SW PRL cells. Mercury, a potent inhibitor
      of AQP3, inhibited hyposmoticity-induced cell volume increase and PRL release
      from FW PRL cells. The inhibitory effect of mercury was partially restored by
      beta-mercaptoethanol, whereas no effect of mercury was observed on PRL release
      stimulated by a depolarizing concentration of KCl, which induces Ca2+ influx and
      stimulates the subsequent Ca2+-signaling pathway. These results indicate
      significant contribution of AQP3 to osmoreception in PRL cells in FW-adapted
      tilapia.

PMID- 19109373
TI  - Mechanisms in the PVN mediating local and central sodium-induced hypertension in
      Wistar rats.
AB  - Sympathoexcitatory and hypertensive responses to central infusion of Na(+)-rich
      artificial cerebrospinal fluid (aCSF) are enhanced by aldosterone and mediated by
      mineralocorticoid receptors (MRs) and benzamil-blockable Na(+) influx, leading to
      "ouabain" release and ANG II type 1 (AT(1)) receptor stimulation. The present
      study evaluated the functional role of these mechanisms in the paraventricular
      nucleus (PVN). In conscious Wistar rats, Na(+)-rich aCSF was infused either
      directly into the PVN or intracerebroventricularly preceded by aldosterone and
      blockers. Infusion of Na(+)-rich aCSF in the PVN caused gradual increases in
      blood pressure (BP) and heart rate (HR). Aldosterone and a subpressor dose of
      ouabain in the PVN alone did not affect BP and HR but enhanced responses to
      Na(+). Eplerenone, benzamil, and "ouabain"-binding Fab fragments only blocked the
      enhancement by aldosterone, whereas losartan blocked all responses to Na(+)-rich
      aCSF in the PVN. Increases in BP and HR by intracerebroventricular infusion of
      Na(+)-rich aCSF were enhanced by aldosterone infused intracerebroventricularly,
      but not in the PVN. Telmisartan in the PVN again blocked all responses. In
      contrast, both eplerenone and benzamil in the PVN did not change the pressor
      responses to intracerebroventricular infusion of aldosterone and Na(+)-rich aCSF.
      These findings indicate that AT(1) receptors in the PVN mediate the responses to
      Na(+)-rich aCSF and their enhancement by aldosterone, both locally in the PVN or
      in the general CSF. MRs, benzamil-blockable Na(+) channels or transporters, and
      "ouabain" can be functionally active in the PVN, but in Wistar rats appear not to
      contribute to the pressor responses to short-term increases in CSF [Na(+)].

PMID- 19109374
TI  - Periodic variation in R-R intervals and cardiovascular autonomic regulation in
      young adult Syrian hamsters.
AB  - Several hamster strains are commonly used as models for cardiomyopathic
      phenotypes evolving toward heart failure. However, little is known about heart
      rate variability (HRV) in this species. Prolonged surface ECG recording, a
      prerequisite to HRV studies, can be obtained either by telemetry or by
      restraints. Here, we performed long time ECG recording using telemetry on young
      adult Syrian hamsters and we analyzed time series of interbeat intervals.
      Standard statistics showed that the mean of normal R-R intervals slightly
      increased with age, with standard deviation of normal R-R intervals remaining
      stable over time. However, time domain analysis using Poincare plots revealed
      dynamic changes in the HRV. Analysis of frequency domains revealed that the ratio
      of spectral components (low frequency/high frequency) exhibited a maturation
      pattern. Thus refined analysis of HRV revealed a more complex pattern than common
      statistical analysis would translate. Unlike other rodents, hamsters display a
      great spontaneous variability of their heart rate. As the complexity canvas of
      HRV might be the consequence of extracardiac regulation factors, we assessed the
      sympathovagal balance in both time and frequency domain of heart rate.
      Pharmacological tests revealed that both sympathetic and vagal tones contribute
      to HRV in Syrian hamsters. Thus Syrian hamsters have a broad intrinsic HRV with
      large influences of the neurovegetative system. However, the influence of the
      previous beat seems to prevail over the autonomic oscillators. These animals
      present a high sensitivity to artificially altered cardiac regulation and might
      be great models for the diagnosis of early alterations in the HRV related to
      pathology. Therefore, Syrian hamsters represent a unique model for HRV studies.

PMID- 19109375
TI  - Cerebral adaptations to chronic anemia in a model of erythropoietin-deficient
      mice exposed to hypoxia.
AB  - Anemia and hypoxia in rats result in an increase in factors potentially involved
      in cerebral angiogenesis. Therefore, the aim of this study was to assess the
      effect of chronic anemia and/or chronic hypoxia on cerebral cellular responses
      and angiogenesis in wild-type and anemic transgenic mice. These studies were done
      in erythropoietin-deficient mice (Epo-TAg(h)) in normoxia and following acute
      (one day) and chronic (14 days, barometric pressure = 420 mmHg) hypoxia. In
      normoxia, Epo-TAg(h) mice showed an increase in transcript and protein levels of
      hypoxia-inducible factor 1alpha (HIF-1alpha), vascular endothelial growth factor
      (VEGF), erythropoietin receptors (EpoR), phospho-STAT-5/STAT-5 ratio, and
      neuronal neuronal nitric oxide synthase (nNOS) along with a higher cerebral
      capillary density. In wild-type (WT) mice, acute hypoxia increased all of the
      studied factors, while in chronic hypoxia, HIF-1alpha, EpoR, phospho-STAT-5/STAT
      5 ratio, nNOS, and inducible NOS remained elevated, with an increase in capillary
      density. Surprisingly, in Epo-TAg(h) mice, chronic hypoxia did not further
      increase any factor except the nitric oxide metabolites, while HIF-1alpha, EpoR,
      and phospho-STAT-5/STAT-5 ratio were reduced. Normoxic Epo-TAg(h) mice developed
      cerebral angiogenesis through the HIF-1alpha/VEGF pathway. In acute hypoxia, WT
      mice up-regulated all of the studied factors, including cerebral NO. Polycythemia
      and angiogenesis occurred with acclimatization to chronic hypoxia only in WT
      mice. In Epo-TAg(h), the decrease in HIF-1alpha, VEGF proteins, and phospho-STAT
      5 ratio in chronic hypoxia suggest that neuroprotective and angiogenesis pathways
      are altered.

PMID- 19109376
TI  - Endotoxin has acute and chronic effects on the cerebral circulation of fetal
      sheep.
AB  - We studied the impact of endotoxemia on cerebral blood flow (CBF), cerebral
      vascular resistance (CVR), and cerebral oxygen transport (O(2) transport) in
      fetal sheep. We hypothesized that endotoxemia impairs CBF regulation and O(2)
      transport, exposing the brain to hypoxic-ischemic injury. Responses to
      lipopolysaccharide (LPS; 1 microg/kg iv on 3 consecutive days, n = 9) or normal
      saline (n = 5) were studied. Of LPS-treated fetuses, five survived and four died;
      in surviving fetuses, transient cerebral vasoconstriction at 0.5 h (DeltaCVR
      approximately +50%) was followed by vasodilatation maximal at 5-6 h (DeltaCVR
      approximately -50%) when CBF had increased (approximately +60%) despite reduced
      ABP (approximately -20%). Decreased CVR and increased CBF persisted 24 h post-LPS
      and the two subsequent LPS infusions. Cerebral O(2) transport was sustained,
      although arterial O(2) saturation was reduced (P < 0.05). Histological evidence
      of neuronal injury was found in all surviving LPS-treated fetuses; one
      experienced grade IV intracranial hemorrhage. Bradykinin-induced cerebral
      vasodilatation (DeltaCVR approximately -20%, P < 0.05) was abolished after LPS.
      Fetuses that died post-LPS (n = 4) differed from survivors in three respects: CVR
      did not fall, CBF did not rise, and O(2) transport fell progressively. In
      conclusion, endotoxin disrupts the cerebral circulation in two phases: 1) acute
      vasoconstriction (1 h) and 2) prolonged vasodilatation despite impaired
      endothelial dilatation (24 h). In surviving fetuses, LPS causes brain injury
      despite cerebral O(2) transport being maintained by elevated cerebral perfusion;
      thus sustained O(2) transport does not prevent brain injury in endotoxemia. In
      contrast, cerebral hypoperfusion and reduced O(2) transport occur in fetuses
      destined to die, emphasizing the importance of sustaining O(2) transport for
      survival.

PMID- 19109377
TI  - Gag p27-specific B- and T-cell responses in Simian immunodeficiency virus SIVagm
      infected African green monkeys.
AB  - Nonpathogenic simian immunodeficiency virus SIVagm infection of African green
      monkeys (AGMs) is characterized by the absence of a robust antibody response
      against Gag p27. To determine if this is accompanied by a selective loss of T
      cell responses to Gag p27, we studied CD4(+) and CD8(+) T-cell responses against
      Gag p27 and other SIVagm antigens in the peripheral blood and lymph nodes of
      acutely and chronically infected AGMs. Our data show that AGMs can mount a T-cell
      response against Gag p27, indicating that the absence of anti-p27 antibodies is
      not due to the absence of Gag p27-specific T cells.

PMID- 19109378
TI  - Role of conserved cysteines in the alphavirus E3 protein.
AB  - Alphavirus particles are covered by 80 glycoprotein spikes that are essential for
      viral entry. Spikes consist of the E2 receptor binding protein and the E1 fusion
      protein. Spike assembly occurs in the endoplasmic reticulum, where E1 associates
      with pE2, a precursor containing E3 and E2 proteins. E3 is a small, cysteine
      rich, extracellular glycoprotein that mediates proper folding of pE2 and its
      subsequent association with E1. In addition, cleavage of E3 from the assembled
      spike is required to make the virus particles efficiently fusion competent. We
      have found that the E3 protein in Sindbis virus contains one disulfide bond
      between residues Cys19 and Cys25. Replacing either of these two critical
      cysteines resulted in mutants with attenuated titers. Replacing both cysteines
      with either alanine or serine resulted in double mutants that were lethal.
      Insertion of additional cysteines based on E3 proteins from other alphaviruses
      resulted in either sequential or nested disulfide bond patterns. E3 sequences
      that formed sequential disulfides yielded virus with near-wild-type titers, while
      those that contained nested disulfide bonds had attenuated activity. Our data
      indicate that the role of the cysteine residues in E3 is not primarily
      structural. We hypothesize that E3 has an enzymatic or functional role in virus
      assembly, and these possibilities are further discussed.

PMID- 19109380
TI  - Efficient replication of human immunodeficiency virus type 1 in resting CD4+ T
      lymphocytes is induced by coculture with autologous dendritic cells in the
      absence of foreign antigens.
AB  - Dendritic cells (DC) are considered to be important contributors to human
      immunodeficiency virus type 1 (HIV-1) transmission and pathogenesis. As the first
      target cells in mucosal tissues, they can be become productively infected and can
      also capture virions and transfer them efficiently to CD4(+) T cells located
      within lymphoid tissues. Resting CD4(+) T cells appear to be another major target
      of HIV-1 in vivo, yet several blocks restrict replication in such cells. We
      report here that physical contact between virus-infected quiescent CD4(+) T cells
      and uninfected autologous immature DC in the absence of any foreign antigen
      relieves these restrictions, allowing a highly productive HIV-1 replication.

PMID- 19109379
TI  - Monoclonal antibodies against the fusion peptide of hemagglutinin protect mice
      from lethal influenza A virus H5N1 infection.
AB  - The HA2 glycopolypeptide (gp) is highly conserved in all influenza A virus
      strains, and it is known to play a major role in the fusion of the virus with the
      endosomal membrane in host cells during the course of viral infection. Vaccines
      and therapeutics targeting this HA2 gp could induce efficient broad-spectrum
      immunity against influenza A virus infections. So far, there have been no studies
      on the possible therapeutic effects of monoclonal antibodies (MAbs), specifically
      against the fusion peptide of hemagglutinin (HA), upon lethal infections with
      highly pathogenic avian influenza (HPAI) H5N1 virus. We have identified MAb 1C9,
      which binds to GLFGAIAGF, a part of the fusion peptide of the HA2 gp. We
      evaluated the efficacy of MAb 1C9 as a therapy for influenza A virus infections.
      This MAb, which inhibited cell fusion in vitro when administered passively,
      protected 100% of mice from challenge with five 50% mouse lethal doses of HPAI
      H5N1 influenza A viruses from two different clades. Furthermore, it caused
      earlier clearance of the virus from the lung. The influenza virus load was
      assessed in lung samples from mice challenged after pretreatment with MAb 1C9 (24
      h prior to challenge) and from mice receiving early treatment (24 h after
      challenge). The study shows that MAb 1C9, which is specific to the antigenically
      conserved fusion peptide of HA2, can contribute to the cross-clade protection of
      mice infected with H5N1 virus and mediate more effective recovery from infection.

PMID- 19109382
TI  - Live chimeric and inactivated Japanese encephalitis virus vaccines differ in
      their cross-protective values against Murray Valley encephalitis virus.
AB  - The Japanese encephalitis virus (JEV) serocomplex, which also includes Murray
      Valley encephalitis virus (MVEV), is a group of antigenically closely related,
      mosquito-borne flaviviruses that are responsible for severe encephalitic disease
      in humans. While vaccines against the prominent members of this serocomplex are
      available or under development, it is unlikely that they will be produced
      specifically against those viruses which cause less-frequent disease, such as
      MVEV. Here we have evaluated the cross-protective values of an inactivated JEV
      vaccine (JE-VAX) and a live chimeric JEV vaccine (ChimeriVax-JE) against MVEV in
      two mouse models of flaviviral encephalitis. We show that (i) a three-dose
      vaccination schedule with JE-VAX provides cross-protective immunity, albeit only
      partial in the more severe challenge model; (ii) a single dose of ChimeriVax-JE
      gives complete protection in both challenge models; (iii) the cross-protective
      immunity elicited with ChimeriVax-JE is durable (>or=5 months) and broad (also
      giving protection against West Nile virus); (iv) humoral and cellular immunities
      elicited with ChimeriVax-JE contribute to protection against lethal challenge
      with MVEV; (v) ChimeriVax-JE remains fully attenuated in immunodeficient mice
      lacking type I and type II interferon responses; and (vi) immunization with JE
      VAX, but not ChimeriVax-JE, can prime heterologous infection enhancement in
      recipients of vaccination on a low-dose schedule, designed to mimic vaccine
      failure or waning of vaccine-induced immunity. Our results suggest that the live
      chimeric JEV vaccine will protect against other viruses belonging to the JEV
      serocomplex, consistent with the observation of cross-protection following live
      virus infections.

PMID- 19109381
TI  - Reduced viral replication capacity of human immunodeficiency virus type 1 subtype
      C caused by cytotoxic-T-lymphocyte escape mutations in HLA-B57 epitopes of capsid
      protein.
AB  - Cytotoxic-T-lymphocyte (CTL) escape mutations in human immunodeficiency viruses
      encode amino acid substitutions in positions that disrupt CTL targeting, thereby
      increasing virus survival and conferring a relative fitness benefit. However, it
      is now clear that CTL escape mutations can also confer a fitness cost, and there
      is increasing evidence to suggest that in some cases, e.g., escape from HLA
      B*57/B*5801-restricted responses, the costs to the escape virus may affect the
      clinical course of infection. To quantify the magnitude of the costs of HLA
      B*57/B*5801 escape, a highly sensitive dual-infection assay that uses synonymous
      nucleotide sequence tags to quantify viral relative replication capacity (RRC)
      was developed. We then asked whether such CTL escape mutations had an impact
      equivalent to that seen for a benchmark mutation, the M184V antiretroviral drug
      resistance mutation of reverse transcriptase (RRC(V184) = 0.86). To answer the
      question, the RRCs were quantified for escape mutations in three immunodominant
      HLA-B*57/B*5801 epitopes in capsid: A146P in IW9 (RRC(P146) = 0.91), A163G in
      KF11 (RRC(G163) = 0.89), and T242N in TW10 (RRC(N242) = 0.86). Individually, the
      impact of the escape mutations on RRC was comparable to that of M184V, while
      coexpression of the mutations resulted in substantial further reductions, with
      the maximum impact observed for the triple mutant (RRC(P146-G163-N242) = 0.62).
      By comparison to M184V, the magnitude of the reductions in RRC caused by the
      escape mutations, particularly when coexpressed, suggests that the costs of
      escape are sufficient to affect in vivo viral dynamics and may thus play a role
      in the protective effect associated with HLA-B*57/B*5801.

PMID- 19109383
TI  - The chromodomain of Tf1 integrase promotes binding to cDNA and mediates target
      site selection.
AB  - The long terminal repeat (LTR) retrotransposon Tf1 of Schizosaccharomyces pombe
      integrates specifically into the promoters of pol II-transcribed genes. Its
      integrase (IN) contains a C-terminal chromodomain related to the chromodomains
      that bind to the N-terminal tail of histone H3. Although we have been unable to
      detect an interaction between histone tails and the chromodomain of Tf1 IN, it is
      possible that the chromodomain plays a role in directing IN to its target sites.
      To test this idea, we generated transposons with single amino acid substitutions
      in highly conserved residues of the chromodomain and created a chromodomain
      deleted mutant. The mutations, V1290A, Y1292A, W1305A, and CHDDelta,
      substantially reduced transposition activity in vivo. Blotting assays showed that
      there was little or no reduction in the levels of IN or cDNA. By measuring the
      homologous recombination between cDNA and the plasmid copy of Tf1, we found that
      two of the mutations did not reduce the import of cDNA into the nucleus, while
      another caused a 33% reduction. Chromatin immunoprecipitation assays revealed
      that CHDDelta caused an approximately threefold reduction in the binding of IN to
      the downstream LTR of the cDNA. These data indicate that the chromodomain
      contributed directly to integration. We therefore tested whether the chromodomain
      contributed to selecting insertion sites. Results of a target plasmid assay
      showed that the deletion of the chromodomain resulted in a drastic reduction in
      the preference for pol II promoters. Collectively, these data indicate that the
      chromodomain promotes binding of cDNA and plays a key role in efficient
      targeting.

PMID- 19109384
TI  - Latent species C adenoviruses in human tonsil tissues.
AB  - Although species C human adenoviruses establish persistent infections, the
      molecular details of this lifestyle remain poorly understood. We previously
      reported that adenovirus DNA is found in human mucosal T lymphocytes in a
      noninfectious form (C. T. Garnett, D. Erdman, W. Xu, and L. R. Gooding, J. Virol.
      76:10608-10616, 2002). In this study, human tonsil and adenoid tissues were
      analyzed to determine the dynamics of infection, the rate of clearance of viral
      DNA, and the possibility of reactivation of virus from these tissues. The
      presence of viral DNA peaked at 4 years of age and declined thereafter. The
      average number of viral genomes declined with the age of the donor. The frequency
      of virus-bearing cells ranged from 3 x 10(-7) to 3.4 x 10(-4), while the amount
      of viral DNA per cell varied less, with an average of 280 copies per cell. All
      species C serotypes were represented in these tissues, although adenovirus type 6
      was notably rare. Infectious virus was detected infrequently (13 of 94 of donors
      tested), even among donors with the highest levels of adenoviral DNA. Adenovirus
      transcripts were rarely detected in uncultured lymphocytes (2 of 12 donors) but
      appeared following stimulation and culture (11 of 13 donors). Viral DNA
      replication could be stimulated in most donor samples by lymphocyte stimulation
      in culture. New infectious virus was detected in 13 of 15 donors following in
      vitro stimulation. These data suggest that species C adenoviruses can establish
      latent infections in mucosal lymphocytes and that stimulation of these cells can
      cause viral reactivation resulting in RNA transcription, DNA replication, and
      infectious virus production.

PMID- 19109385
TI  - Enhancement of adeno-associated virus infection by mobilizing capsids into and
      out of the nucleolus.
AB  - Adeno-associated virus (AAV) serotypes are being tailored for numerous
      therapeutic applications, but the parameters governing the subcellular fate of
      even the most highly characterized serotype, AAV2, remain unclear. To understand
      how cellular conditions control capsid trafficking, we have tracked the
      subcellular fate of recombinant AAV2 (rAAV2) vectors using confocal
      immunofluorescence, three-dimensional infection analysis, and subcellular
      fractionation. Here we report that a population of rAAV2 virions enters the
      nucleus and accumulates in the nucleolus after infection, whereas empty capsids
      are excluded from nuclear entry. Remarkably, after subcellular fractionation,
      virions accumulating in nucleoli were found to retain infectivity in secondary
      infections. Proteasome inhibitors known to enhance transduction were found to
      potentiate nucleolar accumulation. In contrast, hydroxyurea, which also increases
      transduction, mobilized virions into the nucleoplasm, suggesting that two
      separate pathways influence vector delivery in the nucleus. Using a small
      interfering RNA (siRNA) approach, we then evaluated whether nucleolar proteins
      B23/nucleophosmin and nucleolin, previously shown to interact with AAV2 capsids,
      affect trafficking and transduction efficiency. Similar to effects observed with
      proteasome inhibition, siRNA-mediated knockdown of nucleophosmin potentiated
      nucleolar accumulation and increased transduction 5- to 15-fold. Parallel to
      effects from hydroxyurea, knockdown of nucleolin mobilized capsids to the
      nucleoplasm and increased transduction 10- to 30-fold. Moreover, affecting both
      pathways simultaneously using drug and siRNA combinations was synergistic and
      increased transduction over 50-fold. Taken together, these results support the
      hypothesis that rAAV2 virions enter the nucleus intact and can be sequestered in
      the nucleolus in stable form. Mobilization from the nucleolus to nucleoplasmic
      sites likely permits uncoating and subsequent gene expression or genome
      degradation. In summary, with these studies we have refined our understanding of
      AAV2 trafficking dynamics and have identified cellular parameters that mobilize
      virions in the nucleus and significantly influence AAV infection.

PMID- 19109386
TI  - Sharing of endogenous lentiviral gene fragments among leporid lineages separated
      for more than 12 million years.
AB  - Lentiviruses are causal agents of severe pathologies of a variety of mammals,
      including cattle and humans (e.g., AIDS and different types of lymphoma). While
      endogenous forms of lentivirus do not occur in these species, A. Katzourakis and
      coworkers (A. Katzourakis, M. Tristem, O. G. Pybus, and R. J. Gifford, Proc.
      Natl. Acad. Sci. USA 104:6261-6265, 2007) recently reported the presence in the
      genome of the European rabbit (Oryctolagus cuniculus) of multiple sequences
      defining a lentiviral subgroup elegantly referred to as RELIK (rabbit endogenous
      lentivirus type K). Sequence comparisons indicated that the RELIK ancestor may
      have integrated into the rabbit lineage more than 7 million years ago. We have
      substantiated this by producing sequence data certifying the sharing of RELIK
      sequences among leporid lineages that diverged some 12 million years ago.

PMID- 19109387
TI  - Inhibition of a large double-stranded DNA virus by MxA protein.
AB  - Increasing evidence points to the importance of the interferon (IFN) response in
      determining the host range and virulence of African swine fever virus (ASFV).
      Infection with attenuated strains of ASFV leads to the upregulation of genes
      controlled by IFN pathways, including myxovirus resistance (Mx) genes that are
      potent effectors of the antiviral state. Mx gene products are known to inhibit
      the replication of many negative-sense single-stranded RNA viruses, as well as
      double-stranded RNA viruses, positive-sense single-stranded RNA viruses, and the
      reverse-transcribing DNA virus hepatitis B virus. Here, we provide data that
      extend the known range of viruses inhibited by Mx to include the large double
      stranded DNA viruses. Stably transfected Vero cells expressing human MxA protein
      did not support ASFV plaque formation, and virus replication in these cells was
      reduced 100-fold compared with that in control cells. In contrast, ASFV
      replication in cells expressing MxB protein or a mutant MxA protein was similar
      to that in control Vero cells. There was a drastic reduction in ASFV late protein
      synthesis in MxA-expressing cells, correlating with the results of previous work
      on the effect of IFN on viral replication. Strikingly, the inhibition of ASFV
      replication was linked to the recruitment of MxA protein to perinuclear viral
      assembly sites, where the protein surrounded the virus factories. Interactions
      between ASFV and MxA were similar to those seen between MxA and different RNA
      viruses, suggesting a common inhibitory mechanism.

PMID- 19109388
TI  - Arsenic trioxide inhibits hepatitis C virus RNA replication through modulation of
      the glutathione redox system and oxidative stress.
AB  - Arsenic trioxide (ATO), a therapeutic reagent used for the treatment of acute
      promyelocytic leukemia, has recently been reported to increase human
      immunodeficiency virus type 1 infectivity. However, in this study, we have
      demonstrated that replication of genome-length hepatitis C virus (HCV) RNA (O
      strain of genotype 1b) was notably inhibited by ATO at submicromolar
      concentrations without cell toxicity. RNA replication of HCV-JFH1 (genotype 2a)
      and the release of core protein into the culture supernatants were also inhibited
      by ATO after the HCV infection. To clarify the mechanism of the anti-HCV activity
      of ATO, we examined whether or not PML is associated with this anti-HCV activity,
      since PML is known to be a target of ATO. Interestingly, we observed the
      cytoplasmic translocation of PML after treatment with ATO. However, ATO still
      inhibited the HCV RNA replication even in the PML knockdown cells, suggesting
      that PML is dispensable for the anti-HCV activity of ATO. In contrast, we found
      that N-acetyl-cysteine, an antioxidant and glutathione precursor, completely and
      partially eliminated the anti-HCV activity of ATO after 24 h and 72 h of
      treatment, respectively. In this context, it is worth noting that we found an
      elevation of intracellular superoxide anion radical, but not hydrogen peroxide,
      and the depletion of intracellular glutathione in the ATO-treated cells. Taken
      together, these findings suggest that ATO inhibits the HCV RNA replication
      through modulation of the glutathione redox system and oxidative stress.

PMID- 19109389
TI  - Genotyping schemes for polyomavirus BK, using gene-specific phylogenetic trees
      and single nucleotide polymorphism analysis.
AB  - BK virus (BKV) genotyping has been historically based on nucleotides 1744 to 1812
      in the VP1 gene. We reevaluated this practice by making BKV whole-genome and gene
      specific phylogenetic trees as well as performing single nucleotide polymorphism
      (SNP) analysis of 162 sequences available in the public domain. It was found that
      currently known BKV subtypes and subgroups can no longer be reliably determined
      by sequencing certain partial gene sequences. Phylogenetic trees based on large T
      antigen (LTA) allow separation of subtype I into subgroups Ia, Ib1, Ib2, and Ic,
      with bootstrap values of 100%, which are better than bootstraps obtained using
      VP1 sequences (bootstrap values of 71 to 97%). Subtype IV can be subdivided into
      subgroups, but LTA bootstrap values (33 to 80%) are lower than those obtained by
      whole-genome analysis (68 to 87%). Subtypes V and VI provisionally identified
      earlier on the basis of more limited sequence data are better classified as
      subgroups Ib2 and Ib1, respectively. LTA positions 3634, 3772, 3934, and 4339 can
      serve as a minimal SNP set to distinguish between the four major BKV subtypes. No
      subtype II-, IVa-, or IVb-defining SNPs are available in the VP1 gene. However,
      the overall congruence of viral strain classification based on either VP1 or LTA
      phylogenetic analysis indicates that these two areas of the viral genome are
      genetically linked. Interstrain genetic recombination between distant loci in the
      VP1 and LTA areas is not a common event.

PMID- 19109391
TI  - Host responses to wild-type and attenuated herpes simplex virus infection in the
      absence of Stat1.
AB  - Humans and mice lacking the interferon signaling molecule Stat1 are sensitive to
      a variety of pathogens due to their presumed inability to mount a strong innate
      immune response. The herpes simplex virus type 1 (HSV-1) virion host shutoff
      (vhs) protein is a multifunctional immunomodulator that counteracts the innate
      immune response and viruses lacking vhs are attenuated and effective live
      vaccines in animal models. To investigate the interplay of viruses with an
      immunocompromised host, we performed functional genomics analyses on control and
      Stat1(-/-) mouse corneas infected with wild-type or vhs-null viruses. In control
      mice, correlative with viral growth, both viruses induced a transient increase in
      immunomodulators, followed by viral clearance. In contrast, infection of the
      Stat1(-/-) mice induced a heightened and prolonged induction of inflammatory
      modulators for both viruses, manifesting as a significant immune cell infiltrate
      and ocular disease. Moreover, while wild-type virus infection of Stat1(-/-) was
      always lethal, vhs-null infection was rarely lethal. There was a significant
      increase in Stat3- and interleukin-6 (IL-6)-dependent transcription in Stat1(-/-)
      mice, implicating the Stat3 and IL-6 pathways in the observed ocular pathology.
      Further, infected Stat1(-/-) mice showed phosphorylated Stat3 in the corneal
      epithelium. Our data show a role for vhs in evading innate host responses and a
      role for Stat1 in limiting virus infection and for facilitating an appropriate
      nonpathological inflammatory response.

PMID- 19109390
TI  - Reovirus mu2 protein inhibits interferon signaling through a novel mechanism
      involving nuclear accumulation of interferon regulatory factor 9.
AB  - The secreted cytokine alpha/beta interferon (IFN-alpha/beta) binds its receptor
      to activate the Jak-STAT signal transduction pathway, leading to formation of the
      heterotrimeric IFN-stimulated gene factor 3 (ISGF3) transcription complex for
      induction of IFN-stimulated genes (ISGs) and establishment of an antiviral state.
      Many viruses have evolved countermeasures to inhibit the IFN pathway, thereby
      subverting the innate antiviral response. Here, we demonstrate that the mildly
      myocarditic reovirus type 1 Lang (T1L), but not the nonmyocarditic reovirus type
      3 Dearing, represses IFN induction of a subset of ISGs and that this repressor
      function segregates with the T1L M1 gene. Concordantly, the T1L M1 gene product,
      mu2, dramatically inhibits IFN-beta-induced reporter gene expression.
      Surprisingly, T1L infection does not degrade components of the ISGF3 complex or
      interfere with STAT1 or STAT2 nuclear translocation as has been observed for
      other viruses. Instead, infection with T1L or reassortant or recombinant viruses
      containing the T1L M1 gene results in accumulation of interferon regulatory
      factor 9 (IRF9) in the nucleus. This effect has not been previously described for
      any virus and suggests that mu2 modulates IRF9 interactions with STATs for both
      ISGF3 function and nuclear export. The M1 gene is a determinant of virus strain
      specific differences in the IFN response, which are linked to virus strain
      specific differences in induction of murine myocarditis. We find that virus
      induced myocarditis is associated with repression of IFN function, providing new
      insights into the pathophysiology of this disease. Together, these data provide
      the first report of an increase in IRF9 nuclear accumulation associated with
      viral subversion of the IFN response and couple virus strain-specific differences
      in IFN antagonism to the pathogenesis of viral myocarditis.

PMID- 19109392
TI  - Selective uptake of small RNA molecules in the virion of murine gammaherpesvirus
      68.
AB  - Noncoding RNAs are a feature of many herpesvirus genomes. They include microRNAs,
      whose function is the subject of intense investigation, in addition to longer RNA
      molecules such as the Epstein-Barr virus-encoded RNAs and herpesvirus saimiri U
      RNAs, which have been known for some time but whose function is still not well
      defined. Murine gammaherpesvirus 68 (MHV-68) encodes eight viral tRNA-like
      molecules (vtRNAs) of unknown function. Investigating the kinetics of expression
      of the vtRNAs, we observed that they were present directly after infection with
      the virus. This strongly suggested that vtRNAs were part of the virion structure,
      which was confirmed by their detection within various purified, RNase-treated
      preparations. Although both viral and cellular mRNAs were also detected within
      the MHV-68 virion, the major RNA species present were small RNAs of around 70
      nucleotides in length. Interestingly, incorporation of viral mRNA was not related
      to the relative abundance in infected cells, as M11 mRNA, which is present at low
      abundance, was found in virions. MHV-76, which lacks the genes encoding the
      vtRNAs, also incorporated small RNA molecules within the virion, suggesting a
      requirement for these molecules for virion maturation. In productively infected
      cells the vtRNAs localized predominantly within the cytoplasm, although they also
      exhibited a globular pattern of nuclear staining. Their presence in the cytoplasm
      is consistent with interaction with virion components prior to maturation of
      virus particles. The significance of these findings for virion architecture and
      function is discussed.

PMID- 19109393
TI  - Orthopoxviruses require a functional ubiquitin-proteasome system for productive
      replication.
AB  - Cellular homeostasis depends on an intricate balance of protein expression and
      degradation. The ubiquitin-proteasome pathway plays a crucial role in
      specifically targeting proteins tagged with ubiquitin for destruction. This
      degradation can be effectively blocked by both chemically synthesized and natural
      proteasome inhibitors. Poxviruses encode a number of proteins that exploit the
      ubiquitin-proteasome system, including virally encoded ubiquitin molecules and
      ubiquitin ligases, as well as BTB/kelch proteins and F-box proteins, which
      interact with cellular ubiquitin ligases. Here we show that poxvirus infection
      was dramatically affected by a range of proteasome inhibitors, including MG132,
      MG115, lactacystin, and bortezomib (Velcade). Confocal microscopy demonstrated
      that infected cells treated with MG132 or bortezomib lacked viral replication
      factories within the cytoplasm. This was accompanied by the absence of late gene
      expression and DNA replication; however, early gene expression occurred unabated.
      Proteasomal inhibition with MG132 or bortezomib also had dramatic effects on
      viral titers, severely blocking viral replication and propagation. The effects of
      MG132 on poxvirus infection were reversible upon washout, resulting in the
      production of late genes and viral replication factories. Significantly, the
      addition of an ubiquitin-activating enzyme (E1) inhibitor had a similar affect on
      late and early protein expression. Together, our data suggests that a functional
      ubiquitin-proteasome system is required during poxvirus infection.

PMID- 19109394
TI  - Tax1BP1 interacts with papillomavirus E2 and regulates E2-dependent transcription
      and stability.
AB  - The papillomavirus E2 proteins regulate viral replication, gene transcription,
      and genome maintenance by interacting with other viral and host proteins. From a
      yeast two-hybrid screen, we identified the cellular protein Tax1BP1 as a novel
      binding partner of human papillomavirus type 18 (HPV18) E2. Tax1BP1 also
      interacts with the HPV16 and bovine papillomavirus type 1 (BPV1) E2 proteins,
      with the C-terminal region of Tax1BP1 interacting with the N-terminal
      transactivation domain of BPV1 E2. Tax1BP1 complexes with p300 and acts
      synergistically as a coactivator with p300 to enhance E2-dependent transcription.
      Using chromatin immunoprecipitation assays, we show that Tax1BP1 and E2 localize
      to the long control region on the BPV1 genome. Tax1BP1 was recently reported to
      bind ubiquitin and to function as an essential component of an A20 ubiquitin
      editing complex. We demonstrate that Tax1BP1 plays a role in the regulation of
      the steady-state level of E2 by preventing its proteasomal degradation. These
      studies provide new insights into the regulation of E2 functions.

PMID- 19109395
TI  - Expanded breadth of the T-cell response to mosaic human immunodeficiency virus
      type 1 envelope DNA vaccination.
AB  - An effective AIDS vaccine must control highly diverse circulating strains of
      human immunodeficiency virus type 1 (HIV-1). Among HIV-1 gene products, the
      envelope (Env) protein contains variable as well as conserved regions. In this
      report, an informatic approach to the design of T-cell vaccines directed to HIV-1
      Env M group global sequences was tested. Synthetic Env antigens were designed to
      express mosaics that maximize the inclusion of common potential T-cell epitope
      (PTE) 9-mers and minimize the inclusion of rare epitopes likely to elicit strain
      specific responses. DNA vaccines were evaluated using intracellular cytokine
      staining in inbred mice with a standardized panel of highly conserved 15-mer PTE
      peptides. One-, two-, and three-mosaic sets that increased theoretical epitope
      coverage were developed. The breadth and magnitude of T-cell immunity stimulated
      by these vaccines were compared to those for natural strain Envs; additional
      comparisons were performed on mutant Envs, including gp160 or gp145 with or
      without V regions and gp41 deletions. Among them, the two- or three-mosaic Env
      sets elicited the optimal CD4 and CD8 responses. These responses were most
      evident in CD8 T cells; the three-mosaic set elicited responses to an average of
      eight peptide pools, compared to two pools for a set of three natural Envs.
      Synthetic mosaic HIV-1 antigens can therefore induce T-cell responses with
      expanded breadth and may facilitate the development of effective T-cell-based HIV
      1 vaccines.

PMID- 19109396
TI  - Regulation of APOBEC3 proteins by a novel YXXL motif in human immunodeficiency
      virus type 1 Vif and simian immunodeficiency virus SIVagm Vif.
AB  - The APOBEC3 cytidine deaminases are potent antiviral factors that restrict the
      replication of human immunodeficiency virus type 1 (HIV-1). In HIV-1-infected
      CD4+ T cells, the viral accessory protein Vif binds to APOBEC3G (A3G), APOBEC3F
      (A3F), and APOBEC3C (A3C) and targets these proteins for polyubiquitination by
      forming an E3 ubiquitin ligase with cullin 5. Previous studies identified regions
      of HIV-1 Vif, 40YRHHY44 and 12QVDRMR17, which are important for interaction with
      A3G and A3F, respectively, and showed that Vif residues 54 to 71 are sufficient
      for A3G binding. Here, we identify 69YXXL72 as a novel conserved motif in HIV-1
      Vif that mediates binding to human A3G and its subsequent degradation. Studies on
      other APOBEC3 proteins revealed that Tyr69 and Leu72 are important for the
      degradation of A3F and A3C as well. Similar to A3F, A3C regulation is also
      mediated by Vif residues 12QVDRMR17. Simian immunodeficiency virus (SIV) Vif was
      shown to bind and degrade African green monkey A3G (agmA3G) and, unexpectedly,
      human A3C. The YXXL motif of SIVagm Vif was important for the inactivation of
      agmA3G and human A3C. Unlike HIV-1 Vif, however, SIVagm Vif does not require
      Tyr40 and His43 for agmA3G degradation. Tyr69 in the YXXL motif was critical for
      binding of recombinant glutathione S-transferase-Vif(1-94) to A3G in vitro. These
      results suggest that the YXXL motif in Vif is a potential target for small
      molecule inhibitors to block Vif interaction with A3G, A3F, and A3C, and thereby
      protect cells against HIV-1 infection.

PMID- 19109397
TI  - Severe acute respiratory syndrome coronavirus triggers apoptosis via protein
      kinase R but is resistant to its antiviral activity.
AB  - In this study, infection of 293/ACE2 cells with severe acute respiratory syndrome
      coronavirus (SARS-CoV) activated several apoptosis-associated events, namely,
      cleavage of caspase-3, caspase-8, and poly(ADP-ribose) polymerase 1 (PARP), and
      chromatin condensation and the phosphorylation and hence inactivation of the
      eukaryotic translation initiation factor 2alpha (eIF2alpha). In addition, two of
      the three cellular eIF2alpha kinases known to be virus induced, protein kinase R
      (PKR) and PKR-like endoplasmic reticulum kinase (PERK), were activated by SARS
      CoV. The third kinase, general control nonderepressible-2 kinase (GCN2), was not
      activated, but late in infection the level of GCN2 protein was significantly
      reduced. Reverse transcription-PCR analyses revealed that the reduction of GCN2
      protein was not due to decreased transcription or stability of GCN2 mRNA. The
      specific reduction of PKR protein expression by antisense peptide-conjugated
      phosphorodiamidate morpholino oligomers strongly reduced cleavage of PARP in
      infected cells. Surprisingly, the knockdown of PKR neither enhanced SARS-CoV
      replication nor abrogated SARS-CoV-induced eIF2alpha phosphorylation.
      Pretreatment of cells with beta interferon prior to SARS-CoV infection led to a
      significant decrease in PERK activation, eIF2alpha phosphorylation, and SARS-CoV
      replication. The various effects of beta interferon treatment were found to
      function independently on the expression of PKR. Our results show that SARS-CoV
      infection activates PKR and PERK, leading to sustained eIF2alpha phosphorylation.
      However, virus replication was not impaired by these events, suggesting that SARS
      CoV possesses a mechanism to overcome the inhibitory effects of phosphorylated
      eIF2alpha on viral mRNA translation. Furthermore, our data suggest that viral
      activation of PKR can lead to apoptosis via a pathway that is independent of
      eIF2alpha phosphorylation.

PMID- 19109398
TI  - Serum IGF-I, IGFBP-3, and matrix metalloproteinase-7 levels and acquired chemo
      resistance in advanced colorectal cancer.
AB  - Insulin-like growth factor-I (IGF-I) is thought to have antiapoptotic and
      mitogenic properties in colorectal cancer, whereas IGF-binding protein-3 (IGFBP
      3) seems to exert a pro-apoptotic effect. Additionally, matrix metalloproteinase
      7 (MMP-7), an enzyme with in vitro ability to degrade IGFBP-3, has been shown to
      be a prognostic factor in advanced colorectal cancer (ACRC). We studied whether
      chemotherapy treatment for ACRC modulates IGF-I, IGFBP-3, and MMP-7 serum levels.
      In 41 patients undergoing first-line therapy for ACRC, serum levels of IGF-I,
      IGFBP-3, and MMP-7 were measured with immunoassays at baseline and every 3 months
      until progressive disease, or a maximum of five determinations, during a
      chemotherapy regimen of either FOLFOX or FOLFIRI therapies. Associations were
      assessed for paired samples, using t-test or Wilcoxon ranks test depending on
      normality of the variable, verified with Shapiro-Wilk test. An average of four
      extractions (range 3-5) were done, for a total of 157 determinations. Mean
      pretreatment values of IGF-I, IGFBP-3, and MMP-7 were 83 (95% CI, 73-92) ng/ml,
      2372 (95% CI, 2121-2623) ng/ml, and 10.6 (95% CI, 7.21-13.98) ng/ml respectively.
      No significant changes in IGF-I were found, but a significant increase in IGFBP-3
      serum concentrations was observed during or after chemotherapy treatment without
      progressive disease, compared with basal levels (P<0.001). A significant decrease
      in IGFBP-3 to 1983 ng/ml (95% CI, 1675-2292) and a significant increase in MMP-7
      levels to 14.6 (7.6-21.7) ng/ml were observed at progression of disease compared
      with baseline and treatment levels (P<0.001). This study shows that IGFBP-3 and
      MMP-7 serum levels change during chemotherapy treatment. The increased MMP-7
      levels at disease progression support the hypothesis that this protease could
      play a role in acquired resistance by degrading IGFBP-3.

PMID- 19109403
TI  - Beneficial effects of rutin and L-arginine coadministration in a rat model of
      liver ischemia-reperfusion injury.
AB  - Reperfusion following liver ischemia results in oxidative stress leading to liver
      injury. The aim of this study was to investigate the combined effects of two
      antioxidant agents, rutin and L-arginine, in rat liver ischemia-reperfusion
      (I/R). Male Wistar rats were divided into five groups: 1) sham operated, 2) I/R,
      3) I/R+rutin, 4) I/R+L-arginine, and 5) I/R+rutin+L-arginine. Plasmatic and
      hepatic levels of alanine transaminase (ALT), aspartate transaminase (AST), lipid
      peroxides (LOOH), and thiol groups (RSH) were examined, as well as DNA
      fragmentation and liver histopathology. Furthermore, to elucidate the
      pathophysiological processes involved in the antioxidant mechanism(s) of rutin
      and L-arginine, we assessed the expression of inducible (iNOS) and endothelial
      nitric oxide synthase (eNOS) isoforms and heme oxygenase-1 (HO-1), both playing
      key roles in the biochemical cascade of liver injury. Significant increase in
      plasmatic ALT and AST activities were observed in untreated I/R rats compared
      with sham-operated animals, whereas treatment with rutin or L-arginine in I/R
      rats reduced hepatic damage. Interestingly, combined therapy with rutin and L
      arginine resulted in a further reduction of plasmatic ALT and AST activities
      compared with rutin or L-arginine alone. These results were further confirmed by
      the analysis of DNA fragmentation, LOOH, RSH groups, and liver histopathology,
      which showed the highest protective effects following the coadministration of
      rutin and L-arginine. Finally, the combined therapy protocol resulted in a
      significant induction of liver HO-1 and a concomitant reduction of iNOS
      expression that may both be responsible for the beneficial effects of the
      proposed pharmacological protocol.

PMID- 19109404
TI  - Glucagon-like peptide-2 relaxes mouse stomach through vasoactive intestinal
      peptide release.
AB  - Glucagon-like peptide-2 (GLP-2) influences different aspects of the
      gastrointestinal function, including epithelial growth, digestion, absorption,
      motility, and blood flow. Intraluminal pressure from isolated mouse stomach was
      recorded to investigate whether GLP-2 affects gastric tone and to analyze its
      mechanism of action. Regional differences between diverse parts of the stomach
      were also examined using circular muscular strips from fundus and antrum. In the
      whole stomach, GLP-2 (0.3-100 nM) produced concentration-dependent relaxation
      with a maximum that was about 75% of relaxation to 1 microM isoproterenol
      (IC50=2.5 nM). This effect was virtually abolished by desensitization of GLP-2
      receptors or by alpha-chymotrypsin. The relaxant response to GLP-2 was not
      affected by tetrodotoxin, a blocker of neuronal voltage-dependent Na+ channels,
      but it was significantly reduced by omega-conotoxin GVIA, a blocker of neuronal N
      type voltage-operated Ca2+ channels. Nomega-nitro-L-arginine methyl ester, a
      blocker of nitric oxide synthase, or apamin, a blocker of Ca2+-dependent
      potassium channels, failed to affect the gastric response to the peptide.
      However, the relaxation was significantly antagonized by
      [Lys1,Pro2,5,Arg3,4,Tyr6]VIP7-28, a vasoactive intestinal peptide (VIP) receptor
      antagonist (GLP-2 maximum effect=45% of relaxation to 1 microM isoproterenol),
      and virtually abolished by desensitization of the VIP receptors. GLP-2 induced
      concentration-dependent relaxation in carbachol-precontracted fundic strips but
      not in antral strips. These results provide the first experimental evidence that
      GLP-2 is able to induce gastric relaxation acting peripherally on the mouse
      stomach. The effect appears to be mediated by prejunctional neural release of VIP
      and confined to fundic region.

PMID- 19109405
TI  - Human intestinal intraepithelial lymphocytes and epithelial cells coinduce
      interleukin-8 production through the CD2-CD58 interaction.
AB  - Human intestinal CD3+TCRalphabeta+CD8+ intraepithelial lymphocytes (IELs) are
      intimately associated with epithelial cells (ECs) through binding of CD103 to E
      cadherin. How these two cell types functionally interact is largely unknown. IEL
      EC cross talk was determined using HT-29 cells as the model EC and IL-8 as the
      readout. IL-8 was derived from both cell types and synergistically increased when
      the cells were combined. This synergistic effect required active transcription by
      both IELs and HT-29 cells. Cell contact was required as shown by the loss of the
      synergistic increase in IL-8 when the two cell types were separated by
      Transwells. Specifically, IL-8 release required the binding of CD2 on the IELs to
      CD58 on the HT-29 cells. The association of the CD3/TCR complex with major
      histocompatibility antigen class I antigens was not involved. Antibody
      neutralization of tumor necrosis factor-alpha (TNF-alpha), but not interferon
      gamma (IFN-gamma), resulted in increased IL-8 production by the coculture.
      Although both TNF-alpha and IFN-gamma increased IL-8 synthesis and CD58
      expression by the HT-29 cells, only IFN-gamma reduced IL-8 production by IELs. IL
      8 production by either cell type involved phosphorylation of p38 and JNK. In
      summary, the synergistic synthesis of IL-8 occurs when IELs are stimulated
      through the CD2 pathway by CD58 on HT-29 cells, resulting in TNF-alpha release
      that, in turn, augments IL-8 synthesis and CD58 expression by the HT-29 cells.

PMID- 19109406
TI  - KLF4 gene expression is inhibited by the notch signaling pathway that controls
      goblet cell differentiation in mouse gastrointestinal tract.
AB  - In Kruppel-like factor (KLF)-4-deficient mice, colonic goblet cell numbers are
      significantly reduced. Goblet cell development is regulated by the Notch
      signaling pathway. The aim of this study was to examine whether Notch represses
      KLF4 expression to regulate goblet cell differentiation. We first detected that
      KLF4 gene expression was upregulated in a human progastrin-overexpressing mouse
      model where goblet cell hyperplasia has been observed. We then found that mice
      treated with a gamma-secretase inhibitor (compound E, 10 micromol/kg) for 24 h,
      which inhibits the Notch signaling pathway, had significantly increased KLF4 mRNA
      levels in small intestine and colon, accompanied by an increased number of KLF4
      expressing cells at the bottom of crypts in small intestine and colon. In a colon
      cancer cell line (HCT116 cells), KLF4 promoter activity was inhibited by a
      constitutively active form of Notch1 (ICN1) by transient cotransfection assays.
      This inhibition was significantly compromised by a dominant-negative RBPjk, a
      repressive mediator of the Notch signaling pathway. An ICN1-responsive element
      was then mapped in the human KLF4 promoter between -151 and -122 nucleotides
      upstream of the transcriptional start site. It was also found that an intact ICN1
      responsive element is required for ICN1 to inhibit KLF4 promoter activity by
      transient cotransfection assays. Our findings thus reveal a possible mechanism by
      which KLF4 is inhibited by Notch, which controls goblet cell differentiation in
      mouse gastrointestinal tract.

PMID- 19109407
TI  - Establishment of conditionally immortalized epithelial cell lines from the
      intestinal tissue of adult normal and transgenic mice.
AB  - It has proved to be impossible to culture epithelial cells from the
      gastrointestinal tract of adult animals. Researchers have had to use either cell
      lines derived from newborn rat small intestine or colon carcinoma cell lines that
      have retained some of the properties of the gastrointestinal mucosa. We have
      described a method for establishing conditionally immortalized cell lines from
      the stomach, small intestine, colon, pancreas, and liver from tissue obtained
      from a transgenic mouse strain carrying a temperature-sensitive mutant of the
      SV40 large T gene (the "Immortomouse"). This immortalizing gene has proved to be
      useful for establishing cell lines from a number of transgenic mice following
      crossbreeding of the Immortomouse with the transgenic mouse of interest. These
      cell lines are being used in numerous studies. In this review we describe the
      methods for developing such lines and list the range of cell lines that have been
      developed from colon, small intestine, stomach, liver, and pancreas of a number
      of transgenic mice.

PMID- 19109408
TI  - Orlistat accelerates gastric emptying and attenuates GIP release in healthy
      subjects.
AB  - Orlistat, an inhibitor of digestive lipases, is widely used for the treatment of
      obesity. Previous reports on the effect of orally ingested orlistat together with
      a meal on gastric emptying and secretion of gut peptides that modulate
      postprandial responses are controversial. We investigated the effect of ingested
      orlistat on gastric emptying and plasma responses of gut peptides in response to
      a solid mixed meal with a moderate energy load. In healthy subjects, gastric
      emptying was determined using scintigraphy and studies were performed without and
      with 120 mg of orlistat in pellet form in random order. Orlistat shortened t lag
      and t half and decreased the area under the gastric emptying curve. Orlistat
      significantly attenuated the secretion of glucose-dependent insulinotropic
      polypeptide (GIP) but did not alter the plasma responses of cholecystokinin
      (CCK), glucagon-like peptide-1 (GLP-1), pancreatic polypeptide (PP), and insulin.
      There was no peptide YY (PYY) response. Area under the curve of gastric emptying
      was positively correlated with integrated secretion of GIP (r=0.786) in orlistat
      and was negatively correlated with integrated plasma response of GLP-1 (r=-0.75)
      in control experiments, implying that inhibition of fat absorption modifies
      determinants of gastric emptying of a meal. Orlistat administered similar to its
      use in obesity treatment accelerates gastric emptying of a solid mixed meal with
      a moderate energy load and profoundly attenuates release of GIP without
      appreciably altering plasma responses of CCK, GLP-1, and PP. Since GIP is being
      implemented in the development of obesity, its role in weight control attained by
      orlistat awaits further investigation.

PMID- 19109409
TI  - Age-associated changes of extracellular matrix collagen impair lung cancer cell
      migration.
AB  - Although advanced age is linked with an increased incidence of lung carcinomas,
      elderly patients develop fewer metastatic tumors than their younger counterparts.
      Since extracellular matrix controls carcinogenesis, we studied the effect of aged
      fibrillar collagen (rat tail) on the invasiveness of lung carcinoma cells (H322,
      H358). Two- and three-dimensional invasion assays revealed a reduced migration of
      lung cancer cells through a matrix of collagen from old (24 mo) compared with
      young (2 mo) or adult (12 mo) rats. This was most strongly observed for H322
      cells, which had a better migration behavior than H358 cells. Since old collagen
      was increasingly modified by advanced glycation end products (AGEs; fluorescing
      AGEs, nonfluorescing carboxymethyllysine), we generated different AGE-collagens
      by treating collagen with ribose or alpha-dicarbonyls. Similarly to old collagen,
      AGE-collagen reduced the invasive migration of H322 cells. Subsequent analyses
      demonstrated that old and AGE-collagens impair distinct mechanisms contributing
      to cell migration, i.e., efficient cell adhesion and proteolytic degradation of
      collagen by membrane-type matrix metalloproteinase (MT-MMP; MT-MMP3 in H322
      cells). Our data indicate that age-related alterations of the extracellular
      matrix contribute to a less invasive behavior of lung carcinoma cells, in which
      AGE modifications of aged collagen seem to play an important role.

PMID- 19109410
TI  - Proteomic and immunologic analyses of brain tumor exosomes.
AB  - Brain tumors are horrific diseases with almost universally fatal outcomes; new
      therapeutics are desperately needed and will come from improved understandings of
      glioma biology. Exosomes are endosomally derived 30-100 nm membranous vesicles
      released from many cell types into the extracellular milieu; surprisingly,
      exosomes are virtually unstudied in neuro-oncology. These microvesicles were used
      as vaccines in other tumor settings, but their immunological significance is
      unevaluated in brain tumors. Our purpose here is to report the initial
      biochemical, proteomic, and immunological studies on murine brain tumor exosomes,
      following known procedures to isolate exosomes. Our findings show that these
      vesicles have biophysical characteristics and proteomic profiles similar to
      exosomes from other cell types but that brain tumor exosomes have unique features
      (e.g., very basic isoelectric points, expressing the mutated tumor antigen
      EGFRvIII and the putatively immunosuppressive cytokine TGF-beta). Administration
      of such exosomes into syngeneic animals produced both humoral and cellular immune
      responses in immunized hosts capable of rejecting subsequent tumor challenges but
      failed to prolong survival in established orthotopic models. Control animals
      received saline or cell lysate vaccines and showed no antitumor responses.
      Exosomes and microvesicles isolated from sera of patients with brain tumors also
      possess EGFR, EGFRvIII, and TGF-beta. We conclude that exosomes released from
      brain tumor cells are biochemically/biophysically like other exosomes and have
      immune-modulating properties. They can escape the blood-brain barrier, with
      potential systemic and distal signaling and immune consequences.

PMID- 19109411
TI  - Thylakoid membrane reduction affects the photosystem stoichiometry in the
      cyanobacterium Synechocystis sp. PCC 6803.
AB  - Biogenesis of thylakoid membranes in both chloroplasts and cyanobacteria is
      largely not understood today. The vesicle-inducing protein in plastids 1 (Vipp1)
      has been suggested to be essential for thylakoid membrane formation in
      Arabidopsis (Arabidopsis thaliana), as well as in the cyanobacterium
      Synechocystis sp. PCC 6803, although its exact physiological function remains
      elusive so far. Here, we report that, upon depletion of Vipp1 in Synechocystis
      cells, the number of thylakoid layers in individual Synechocystis cells
      decreased, and that, in particular, the content of photosystem I (PSI) complexes
      was highly diminished in thylakoids. Furthermore, separation of native
      photosynthetic complexes indicated that PSI trimers are destabilized and the
      monomeric species is enriched. Therefore, depletion of thylakoid membranes
      specifically affects biogenesis and/or stabilization of PSI in cyanobacteria.

PMID- 19109412
TI  - Mitogen-activated protein kinase cascades and ethylene: signaling, biosynthesis,
      or both?

PMID- 19109413
TI  - Reactive oxygen species production by potato tuber mitochondria is modulated by
      mitochondrially bound hexokinase activity.
AB  - Potato tuber (Solanum tuberosum) mitochondria (PTM) have a mitochondrially bound
      hexokinase (HK) activity that exhibits a pronounced sensitivity to ADP
      inhibition. Here we investigated the role of mitochondrial HK activity in PTM
      reactive oxygen species generation. Mitochondrial HK has a 10-fold higher
      affinity for glucose (Glc) than for fructose (KMGlc=140 microM versus KMFrc=1,375
      microM). Activation of PTM respiration by succinate led to an increase in
      hydrogen peroxide (H2O2) release that was abrogated by mitochondrial HK
      activation. Mitochondrial HK activity caused a decrease in the mitochondrial
      membrane potential and an increase in oxygen consumption by PTM. Inhibition of
      Glc phosphorylation by mannoheptulose or GlcNAc induced a rapid increase in H2O2
      release. The blockage of H2O2 release sustained by Glc was reverted by oligomycin
      and atractyloside, indicating that ADP recycles through the adenine nucleotide
      translocator and F0F1ATP synthase is operative during the mitochondrial HK
      reaction. Inhibition of mitochondrial HK activity by 60% to 70% caused an
      increase of 50% in the maximal rate of H2O2 release. Inhibition in H2O2 release
      by mitochondrial HK activity was comparable to, or even more potent, than that
      observed for StUCP (S. tuberosum uncoupling protein) activity. The inhibition of
      H2O2 release in PTM was two orders of magnitude more selective for the ADP
      produced from the mitochondrial HK reaction than for that derived from soluble
      yeast (Saccharomyces cerevisiae) HK. Modulation of H2O2 release and oxygen
      consumption by Glc and mitochondrial HK inhibitors in potato tuber slices shows
      that hexoses and mitochondrial HK may act as a potent preventive antioxidant
      mechanism in potato tubers.

PMID- 19109414
TI  - A small family of chloroplast atypical thioredoxins.
AB  - The reduction and the formation of regulatory disulfide bonds serve as a key
      signaling element in chloroplasts. Members of the thioredoxin (Trx) superfamily
      of oxidoreductases play a major role in these processes. We have characterized a
      small family of plant-specific Trxs in Arabidopsis (Arabidopsis thaliana) that
      are rich in cysteine and histidine residues and are typified by a variable
      noncanonical redox active site. We found that the redox midpoint potential of
      three selected family members is significantly less reducing than that of the
      classic Trxs. Assays of subcellular localization demonstrated that all proteins
      are localized to the chloroplast. Selected members showed high activity,
      contingent on a dithiol electron donor, toward the chloroplast 2-cysteine
      peroxiredoxin A and poor activity toward the chloroplast NADP-malate
      dehydrogenase. The expression profile of the family members suggests that they
      have distinct roles. The intermediate redox midpoint potential value of the
      atypical Trxs might imply adaptability to function in modulating the redox state
      of chloroplast proteins with regulatory disulfides.

PMID- 19109415
TI  - A rice kinase-protein interaction map.
AB  - Plants uniquely contain large numbers of protein kinases, and for the vast
      majority of the 1,429 kinases predicted in the rice (Oryza sativa) genome, little
      is known of their functions. Genetic approaches often fail to produce observable
      phenotypes; thus, new strategies are needed to delineate kinase function. We
      previously developed a cost-effective high-throughput yeast two-hybrid system.
      Using this system, we have generated a protein interaction map of 116
      representative rice kinases and 254 of their interacting proteins. Overall, the
      resulting interaction map supports a large number of known or predicted kinase
      protein interactions from both plants and animals and reveals many new functional
      insights. Notably, we found a potential widespread role for E3 ubiquitin ligases
      in pathogen defense signaling mediated by receptor-like kinases, particularly by
      the kinases that may have evolved from recently expanded kinase subfamilies in
      rice. We anticipate that the data provided here will serve as a foundation for
      targeted functional studies in rice and other plants. The application of yeast
      two-hybrid and TAPtag analyses for large-scale plant protein interaction studies
      is also discussed.

PMID- 19109416
TI  - CYP86A33-targeted gene silencing in potato tuber alters suberin composition,
      distorts suberin lamellae, and impairs the periderm's water barrier function.
AB  - Suberin is a cell wall lipid polyester found in the cork cells of the periderm
      offering protection against dehydration and pathogens. Its biosynthesis and
      assembly, as well as its contribution to the sealing properties of the periderm,
      are still poorly understood. Here, we report on the isolation of the coding
      sequence CYP86A33 and the molecular and physiological function of this gene in
      potato (Solanum tuberosum) tuber periderm. CYP86A33 was down-regulated in potato
      plants by RNA interference-mediated silencing. Periderm from CYP86A33-silenced
      plants revealed a 60% decrease in its aliphatic suberin load and greatly reduced
      levels of C18:1 omega-hydroxyacid (approximately 70%) and alpha,omega-diacid
      (approximately 90%) monomers in comparison with wild type. Moreover, the glycerol
      esterified to suberin was reduced by 60% in the silenced plants. The typical
      regular ultrastructure of suberin, consisting of dark and light lamellae,
      disappeared and the thickness of the suberin layer was clearly reduced. In
      addition, the water permeability of the periderm isolated from CYP86A33-silenced
      lines was 3.5 times higher than that of the wild type. Thus, our data provide
      convincing evidence for the involvement of omega-functional fatty acids in
      establishing suberin structure and function.

PMID- 19109418
TI  - Discrete determinants in ArfGAP2/3 conferring Golgi localization and regulation
      by the COPI coat.
AB  - From yeast to mammals, two types of GTPase-activating proteins, ArfGAP1 and
      ArfGAP2/3, control guanosine triphosphate (GTP) hydrolysis on the small G protein
      ADP-ribosylation factor (Arf) 1 at the Golgi apparatus. Although functionally
      interchangeable, they display little similarity outside the catalytic GTPase
      activating protein (GAP) domain, suggesting differential regulation. ArfGAP1 is
      controlled by membrane curvature through its amphipathic lipid packing sensor
      motifs, whereas Golgi targeting of ArfGAP2 depends on coatomer, the building
      block of the COPI coat. Using a reporter fusion approach and in vitro assays, we
      identified several functional elements in ArfGAP2/3. We show that the Golgi
      localization of ArfGAP3 depends on both a central basic stretch and a carboxy
      amphipathic motif. The basic stretch interacts directly with coatomer, which we
      found essential for the catalytic activity of ArfGAP3 on Arf1-GTP, whereas the
      carboxy-amphipathic motif interacts directly with lipid membranes but has minor
      role in the regulation of ArfGAP3 activity. Our findings indicate that the two
      types of ArfGAP proteins that reside at the Golgi use a different combination of
      protein-protein and protein-lipid interactions to promote GTP hydrolysis in Arf1
      GTP.

PMID- 19109417
TI  - Systematic analysis in Caenorhabditis elegans reveals that the spindle checkpoint
      is composed of two largely independent branches.
AB  - Kinetochores use the spindle checkpoint to delay anaphase onset until all
      chromosomes have formed bipolar attachments to spindle microtubules. Here, we use
      controlled monopolar spindle formation to systematically define the requirements
      for spindle checkpoint signaling in the Caenorhabditis elegans embryo. The
      results, when interpreted in light of kinetochore assembly epistasis analysis,
      indicate that checkpoint activation is coordinately directed by the NDC-80
      complex, the Rod/Zwilch/Zw10 complex, and BUB-1-three components independently
      targeted to the outer kinetochore by the scaffold protein KNL-1. These components
      orchestrate the integration of a core Mad1(MDF-1)/Mad2(MDF-2)-based signal, with
      a largely independent Mad3(SAN-1)/BUB-3 pathway. Evidence for independence comes
      from the fact that subtly elevating Mad2(MDF-2) levels bypasses the requirement
      for BUB-3 and Mad3(SAN-1) in kinetochore-dependent checkpoint activation.
      Mad3(SAN-1) does not accumulate at unattached kinetochores and BUB-3 kinetochore
      localization is independent of Mad2(MDF-2). We discuss the rationale for a
      bipartite checkpoint mechanism in which a core Mad1(MDF-1)/Mad2(MDF-2) signal
      generated at kinetochores is integrated with a separate cytoplasmic Mad3(SAN
      1)/BUB-3-based pathway.

PMID- 19109419
TI  - A link between FXYD3 (Mat-8)-mediated Na,K-ATPase regulation and differentiation
      of Caco-2 intestinal epithelial cells.
AB  - FXYD3 (Mat-8) proteins are regulators of Na,K-ATPase. In normal tissue, FXYD3 is
      mainly expressed in stomach and colon, but it is also overexpressed in cancer
      cells, suggesting a role in tumorogenesis. We show that FXYD3 silencing has no
      effect on cell proliferation but promotes cell apoptosis and prevents cell
      differentiation of human colon adenocarcinoma cells (Caco-2), which is reflected
      by a reduction in alkaline phosphatase and villin expression, a change in several
      other differentiation markers, and a decrease in transepithelial resistance.
      Inhibition of cell differentiation in FXYD3-deficient cells is accompanied by an
      increase in the apparent Na+ and K+ affinities of Na,K-ATPase, reflecting the
      absence of Na,K-pump regulation by FXYD3. In addition, we observe a decrease in
      the maximal Na,K-ATPase activity due to a decrease in its turnover number, which
      correlates with a change in Na,K-ATPase isozyme expression that is characteristic
      of cancer cells. Overall, our results suggest an important role of FXYD3 in cell
      differentiation of Caco-2 cells. One possibility is that FXYD3 silencing prevents
      proper regulation of Na,K-ATPase, which leads to perturbation of cellular Na+ and
      K+ homeostasis and changes in the expression of Na,K-ATPase isozymes, whose
      functional properties are incompatible with Caco-2 cell differentiation.

PMID- 19109421
TI  - GM130-dependent control of Cdc42 activity at the Golgi regulates centrosome
      organization.
AB  - The physical proximity of the Golgi apparatus and the centrosome is a unique
      feature of mammalian cells whose functional significance is only poorly
      understood. Here, we demonstrate that the previously described regulation of
      centrosome organization and function by the Golgi protein, GM130, involves a
      Golgi-associated complex consisting of GM130, the Rho GTPase, Cdc42, and its
      guanine nucleotide exchange factor, Tuba. We identified Tuba as a novel GM130
      interacting protein and showed that this association controls Tuba-mediated
      activation of Cdc42 at the Golgi apparatus. Blocking either Tuba or Cdc42
      activity reproduced the GM130 depletion phenotype of aberrant, nonfunctional
      centrosomes. Expression of constitutively active Cdc42 bypassed the requirement
      for GM130 in centrosome regulation, indicating that Cdc42 functions downstream of
      GM130. Our studies demonstrate that Cdc42 has a novel role in controlling
      centrosome organization in unstimulated cells in addition to its known function
      as a regulator of centrosome reorientation in stimulated cells. This first
      description of a regulatory pathway between the Golgi apparatus and the
      interphase centrosome that complements the known role of Golgi proteins in
      controlling spindle formation during mitosis and may provide an explanation for
      the pericentriolar position of the mammalian Golgi apparatus during interphase.

PMID- 19109420
TI  - Supervillin reorganizes the actin cytoskeleton and increases invadopodial
      efficiency.
AB  - Tumor cells use actin-rich protrusions called invadopodia to degrade
      extracellular matrix (ECM) and invade tissues; related structures, termed
      podosomes, are sites of dynamic ECM interaction. We show here that supervillin
      (SV), a peripheral membrane protein that binds F-actin and myosin II, reorganizes
      the actin cytoskeleton and potentiates invadopodial function. Overexpressed SV
      induces redistribution of lamellipodial cortactin and lamellipodin/RAPH1/PREL1
      away from the cell periphery to internal sites and concomitantly increases the
      numbers of F-actin punctae. Most punctae are highly dynamic and colocalize with
      the podosome/invadopodial proteins, cortactin, Tks5, and cdc42. Cortactin binds
      SV sequences in vitro and contributes to the formation of enhanced green
      fluorescent protein (EGFP)-SV induced punctae. SV localizes to the cores of Src
      generated podosomes in COS-7 cells and with invadopodia in MDA-MB-231 cells. EGFP
      SV overexpression increases average numbers of ECM holes per cell; RNA
      interference-mediated knockdown of SV decreases these numbers. Although SV
      knockdown alone has no effect, simultaneous down-regulation of SV and the closely
      related protein gelsolin reduces invasion through ECM. Together, our results show
      that SV is a component of podosomes and invadopodia and that SV plays a role in
      invadopodial function, perhaps as a mediator of cortactin localization,
      activation state, and/or dynamics of metalloproteinases at the ventral cell
      surface.

PMID- 19109422
TI  - Autophagy provides nutrients but can lead to Chop-dependent induction of Bim to
      sensitize growth factor-deprived cells to apoptosis.
AB  - Tissue homeostasis is controlled by the availability of growth factors, which
      sustain exogenous nutrient uptake and prevent apoptosis. Although autophagy can
      provide an alternate intracellular nutrient source to support essential basal
      metabolism of apoptosis-resistant growth factor-withdrawn cells, antiapoptotic
      Bcl-2 family proteins can suppress autophagy in some settings. Thus, the role of
      autophagy and interactions between autophagy and apoptosis in growth factor
      withdrawn cells expressing Bcl-2 or Bcl-xL were unclear. Here we show autophagy
      was rapidly induced in hematopoietic cells upon growth factor withdrawal
      regardless of Bcl-2 or Bcl-xL expression and led to increased mitochondrial lipid
      oxidation. Deficiency in autophagy-essential gene expression, however, did not
      lead to metabolic catastrophe and rapid death of growth factor-deprived cells.
      Rather, inhibition of autophagy enhanced survival of cells with moderate Bcl-2
      expression for greater than 1 wk, indicating that autophagy promoted cell death
      in this time frame. Cell death was not autophagic, but apoptotic, and relied on
      Chop-dependent induction of the proapoptotic Bcl-2 family protein Bim. Therefore,
      although ultimately important, autophagy-derived nutrients appear initially
      nonessential after growth factor withdrawal. Instead, autophagy promotes tissue
      homeostasis by sensitizing cells to apoptosis to ensure only the most apoptosis
      resistant cells survive long-term using autophagy-derived nutrients when growth
      factor deprived.

PMID- 19109423
TI  - The anaphase-promoting complex promotes actomyosin-ring disassembly during
      cytokinesis in yeast.
AB  - The anaphase-promoting complex (APC) is a ubiquitin ligase that controls
      progression through mitosis by targeting specific proteins for degradation. It is
      unclear whether the APC also contributes to the control of cytokinesis, the
      process that divides the cell after mitosis. We addressed this question in the
      yeast Saccharomyces cerevisiae by studying the effects of APC mutations on the
      actomyosin ring, a structure containing actin, myosin, and several other proteins
      that forms at the division site and is important for cytokinesis. In wild-type
      cells, actomyosin-ring constituents are removed progressively from the ring
      during contraction and disassembled completely thereafter. In cells lacking the
      APC activator Cdh1, the actomyosin ring contracts at a normal rate, but ring
      constituents are not disassembled normally during or after contraction. After
      cytokinesis in mutant cells, aggregates of ring proteins remain at the division
      site and at additional foci in other parts of the cell. A key target of APC(Cdh1)
      is the ring component Iqg1, the destruction of which contributes to actomyosin
      ring disassembly. Deletion of CDH1 also exacerbates actomyosin-ring disassembly
      defects in cells with mutations in the myosin light-chain Mlc2, suggesting that
      Mlc2 and the APC employ independent mechanisms to promote ring disassembly during
      cytokinesis.

PMID- 19109424
TI  - A histone deacetylase 4/myogenin positive feedback loop coordinates denervation
      dependent gene induction and suppression.
AB  - Muscle activity contributes to formation of the neuromuscular junction and
      affects muscle metabolism and contractile properties through regulated gene
      expression. However, the mechanisms coordinating these diverse activity-regulated
      processes remain poorly characterized. Recently, it was reported that histone
      deacetylase 4 (HDAC4) can mediate denervation-induced myogenin and nicotinic
      acetylcholine receptor gene expression. Here, we report that HDAC4 is not only
      necessary for denervation-dependent induction of genes involved in synaptogenesis
      (nicotinic acetylcholine receptor and muscle-specific receptor tyrosine kinase)
      but also for denervation-dependent suppression of genes involved in glycolysis
      (muscle-specific enolase and phosphofructokinase). In addition, HDAC4
      differentially regulates genes involved in muscle fiber type specification by
      inducing myosin heavy chain IIA and suppressing myosin heavy chain IIB.
      Consistent with these regulated gene profiles, HDAC4 is enriched in fast
      oxidative fibers of innervated tibialis anterior muscle and HDAC4 knockdown
      enhances glycolysis in cultured myotubes. HDAC4 mediates gene induction
      indirectly by suppressing the expression of Dach2 and MITR that function as
      myogenin gene corepressors. In contrast, HDAC4 is directly recruited to myocyte
      enhancer factor 2 sites within target promoters to mediate gene suppression.
      Finally, we discovered an HDAC4/myogenin positive feedback loop that coordinates
      gene induction and repression underlying muscle phenotypic changes after muscle
      denervation.

PMID- 19109426
TI  - Deficient SUMO attachment to Flp recombinase leads to homologous recombination
      dependent hyperamplification of the yeast 2 microm circle plasmid.
AB  - Many Saccharomyces cerevisiae mutants defective in the SUMO pathway accumulate
      elevated levels of the native 2 microm circle plasmid (2 microm). Here we show
      that accumulation of 2 microm in the SUMO pathway mutants siz1Delta siz2Delta,
      slx5Delta, and slx8Delta is associated with formation of an aberrant high
      molecular-weight (HMW) form of 2 microm. Characterization of this species from
      siz1Delta siz2Delta showed that it contains tandem copies of the 2 mum sequence
      as well as single-stranded DNA. Accumulation of this species requires both the 2
      microm-encoded Flp recombinase and the cellular homologous recombination repair
      (HRR) pathway. Importantly, reduced SUMO attachment to Flp is sufficient to
      induce formation of this species. Our data suggest a model in which Flp that
      cannot be sumoylated causes DNA damage, whose repair via HRR produces an
      intermediate that generates tandem copies of the 2 microm sequence. This
      intermediate may be a rolling circle formed via break-induced replication (BIR),
      because mutants defective in BIR contain reduced levels of the HMW form. This
      work also illustrates the importance of using cir(o) strains when studying
      mutants that affect the yeast SUMO pathway, to avoid confusing direct functions
      of the SUMO pathway with secondary effects of 2 microm amplification.

PMID- 19109425
TI  - SPE-39 family proteins interact with the HOPS complex and function in lysosomal
      delivery.
AB  - Yeast and animal homotypic fusion and vacuole protein sorting (HOPS) complexes
      contain conserved subunits, but HOPS-mediated traffic in animals might require
      additional proteins. Here, we demonstrate that SPE-39 homologues, which are found
      only in animals, are present in RAB5-, RAB7-, and RAB11-positive endosomes where
      they play a conserved role in lysosomal delivery and probably function via their
      interaction with the core HOPS complex. Although Caenorhabditis elegans spe-39
      mutants were initially identified as having abnormal vesicular biogenesis during
      spermatogenesis, we show that these mutants also have disrupted processing of
      endocytosed proteins in oocytes and coelomocytes. C. elegans SPE-39 interacts in
      vitro with both VPS33A and VPS33B, whereas RNA interference of VPS33B causes spe
      39-like spermatogenesis defects. The human SPE-39 orthologue C14orf133 also
      interacts with VPS33 homologues and both coimmunoprecipitates and cosediments
      with other HOPS subunits. SPE-39 knockdown in cultured human cells altered the
      morphology of syntaxin 7-, syntaxin 8-, and syntaxin 13-positive endosomes. These
      effects occurred concomitantly with delayed mannose 6-phosphate receptor-mediated
      cathepsin D delivery and degradation of internalized epidermal growth factor
      receptors. Our findings establish that SPE-39 proteins are a previously
      unrecognized regulator of lysosomal delivery and that C. elegans spermatogenesis
      is an experimental system useful for identifying conserved regulators of metazoan
      lysosomal biogenesis.

PMID- 19109427
TI  - A shared mechanism of adhesion modulation for tenascin-C and fibulin-1.
AB  - Adhesion modulatory proteins are important effectors of cell-matrix interactions
      during tissue remodeling and regeneration. They comprise a diverse group of
      matricellular proteins that confer antiadhesive properties to the extracellular
      matrix (ECM). We compared the inhibitory effects of two adhesion modulatory
      proteins, fibulin-1 and tenascin-C, both of which bind to the C-terminal heparin
      binding (HepII) domain of fibronectin (FN) but are structurally distinct. Here,
      we report that, like tenascin-C, fibulin-1 inhibits fibroblast spreading and cell
      mediated contraction of a fibrin-FN matrix. These proteins act by modulation of
      focal adhesion kinase and extracellular signal-regulated kinase signaling. The
      inhibitory effects were bypassed by lysophosphatidic acid, an activator of RhoA
      GTPase. Fibroblast response to fibulin-1, similar to tenascin-C, was dependent on
      expression of the heparan sulfate proteoglycan syndecan-4, which also binds to
      the HepII domain. Therefore, blockade of HepII-mediated signaling by competitive
      binding of fibulin-1 or tenascin-C represents a shared mechanism of adhesion
      modulation among disparate modulatory proteins.

PMID- 19109428
TI  - Molecular architecture of the centriole proteome: the conserved WD40 domain
      protein POC1 is required for centriole duplication and length control.
AB  - Centrioles are intriguing cylindrical organelles composed of triplet
      microtubules. Proteomic data suggest that a large number of proteins besides
      tubulin are necessary for the formation and maintenance of a centriole's complex
      structure. Expansion of the preexisting centriole proteome from the green alga
      Chlamydomonas reinhardtii revealed additional human disease genes, emphasizing
      the significance of centrioles in normal human tissue homeostasis. We found that
      two classes of ciliary disease genes were highly represented among the basal body
      proteome: cystic kidney disease (especially nephronophthisis) syndromes,
      including Meckel/Joubert-like and oral-facial-digital syndrome, caused by
      mutations in CEP290, MKS1, OFD1, and AHI1/Jouberin proteins and cone-rod
      dystrophy syndrome genes, including UNC-119/HRG4, NPHP4, and RPGR1. We further
      characterized proteome of the centriole (POC) 1, a highly abundant WD40 domain
      containing centriole protein. We found that POC1 is recruited to nascent
      procentrioles and localizes in a highly asymmetrical pattern in mature centrioles
      corresponding to sites of basal-body fiber attachment. Knockdown of POC1 in human
      cells caused a reduction in centriole duplication, whereas overexpression caused
      the appearance of elongated centriole-like structures. Together, these data
      suggest that POC1 is involved in early steps of centriole duplication as well as
      in the later steps of centriole length control.

PMID- 19109429
TI  - GINS inactivation phenotypes reveal two pathways for chromatin association of
      replicative alpha and epsilon DNA polymerases in fission yeast.
AB  - The tetrameric GINS complex, consisting of Sld5-Psf1-Psf2-Psf3, plays an
      essential role in the initiation and elongation steps of eukaryotic DNA
      replication, although its biochemical function is unclear. Here we investigate
      the function of GINS in fission yeast, using fusion of Psf1 and Psf2 subunits to
      a steroid hormone-binding domain (HBD) to make GINS function conditional on the
      presence of beta-estradiol. We show that inactivation of Psf1-HBD causes a tight
      but rapidly reversible DNA replication arrest phenotype. Inactivation of Psf2-HBD
      similarly blocks premeiotic DNA replication and leads to loss of nuclear
      localization of another GINS subunit, Psf3. Inactivation of GINS has distinct
      effects on the replication origin association and chromatin binding of two of the
      replicative DNA polymerases. Inactivation of Psf1 leads to loss of chromatin
      binding of DNA polymerase epsilon, and Cdc45 is similarly affected. In contrast,
      chromatin association of the catalytic subunit of DNA polymerase alpha is not
      affected by defective GINS function. We suggest that GINS functions in a pathway
      that involves Cdc45 and is necessary for DNA polymerase epsilon chromatin
      binding, but that a separate pathway sets up the chromatin association of DNA
      polymerase alpha.

PMID- 19109430
TI  - Dorsal root ganglion neurons react to semaphorin 3A application through a
      biphasic response that requires multiple myosin II isoforms.
AB  - Growth cone responses to guidance cues provide the basis for neuronal
      pathfinding. Although many cues have been identified, less is known about how
      signals are translated into the cytoskeletal rearrangements that steer
      directional changes during pathfinding. Here we show that the response of dorsal
      root ganglion (DRG) neurons to Semaphorin 3A gradients can be divided into two
      steps: growth cone collapse and retraction. Collapse is inhibited by
      overexpression of myosin IIA or growth on high substrate-bound laminin-1.
      Inhibition of collapse also prevents retractions; however collapse can occur
      without retraction. Inhibition of myosin II activity with blebbistatin or by
      using neurons from myosin IIB knockouts inhibits retraction. Collapse is
      associated with movement of myosin IIA from the growth cone to the neurite.
      Myosin IIB redistributes from a broad distribution to the rear of the growth cone
      and neck of the connecting neurite. High substrate-bound laminin-1 prevents or
      reverses these changes. This suggests a model for the Sema 3A response that
      involves loss of growth cone myosin IIA to facilitate actin meshwork instability
      and collapse, followed by myosin IIB concentration at the rear of the cone and
      neck region where it associates with actin bundles to drive retraction.

PMID- 19109431
TI  - Trophic cascades promote threshold-like shifts in pelagic marine ecosystems.
AB  - Fisheries can have a large impact on marine ecosystems, because the effects of
      removing large predatory fish may cascade down the food web. The implications of
      these cascading processes on system functioning and resilience remain a source of
      intense scientific debate. By using field data covering a 30-year period, we show
      for the Baltic Sea that the underlying mechanisms of trophic cascades produced a
      shift in ecosystem functioning after the collapse of the top predator cod. We
      identified an ecological threshold, corresponding to a planktivore abundance of
      approximately 17 x 10(10) individuals, that separates 2 ecosystem configurations
      in which zooplankton dynamics are driven by either hydroclimatic forces or
      predation pressure. Abundances of the planktivore sprat above the threshold
      decouple zooplankton dynamics from hydrological circumstances. The current strong
      regulation by sprat of the feeding resources for larval cod may hinder cod
      recovery and the return of the ecosystem to a prior state. This calls for the
      inclusion of a food web perspective in management decisions.

PMID- 19109432
TI  - Great ranging associated with greater reproductive investment in mammals.
AB  - Most animals must travel to find food, incurring an unavoidable energy and time
      cost. Economic theory predicts, and experimental work confirms, that within
      species, increasing the distance traveled each day to find food has negative
      fitness consequences, decreasing the amount of energy invested in maintenance,
      repair, and reproduction. Here, we show that this relationship between daily
      distance traveled and reproductive success is fundamentally different between
      species and over evolutionary time in many lineages. Phylogenetically controlled
      analyses of 161 eutherian mammals indicate that, after controlling for body mass,
      evolutionary increases in the daily distance traveled are associated with
      corresponding increases in both total fertility (number of offspring per
      lifetime) and total offspring mass (grams of offspring per lifetime). This
      suggests that over evolutionary time, increasing travel distance is often part of
      a strategy for procuring more food energy and not necessarily a response to
      decreased food availability. These results have important implications for
      ecological comparisons among species, including assessments of habitat quality
      based on locomotor behavior.

PMID- 19109433
TI  - Reprogramming of murine and human somatic cells using a single polycistronic
      vector.
AB  - Directed reprogramming of somatic cells by defined factors provides a novel
      method for the generation of patient-specific stem cells with the potential to
      bypass both the practical and ethical concerns associated with somatic cell
      nuclear transfer (SCNT) and human embryonic stem (hES) cells. Although the
      generation of induced pluripotent stem (iPS) cells has proven a robust technology
      in mouse and human, a major impediment to the use of iPS cells for therapeutic
      purposes has been the viral-based delivery of the reprogramming factors because
      multiple proviral integrations pose the danger of insertional mutagenesis. Here
      we report a novel approach to reduce the number of viruses necessary to reprogram
      somatic cells by delivering reprogramming factors in a single virus using 2A
      "self-cleaving" peptides, which support efficient polycistronic expression from a
      single promoter. We find that up to four reprogramming factors (Oct4, Sox2, Klf4,
      and c-Myc) can be expressed from a single virus to generate iPS cells in both
      embryonic and adult somatic mouse cells and we show that a single proviral copy
      is sufficient to generate iPS cells from mouse embryonic fibroblasts. In addition
      we have generated human induced pluripotent stem (hiPS) cell lines from human
      keratinocytes, demonstrating that a single polycistronic virus can reprogram
      human somatic cells.

PMID- 19109434
TI  - Disruption of the SRC-1 gene in mice suppresses breast cancer metastasis without
      affecting primary tumor formation.
AB  - Steroid receptor coactivator-1 (SRC-1) is a coactivator for nuclear hormone
      receptors such as estrogen and progesterone receptors and certain other
      transcription factors such as Ets-2 and PEA3. SRC-1 expression in breast cancer
      is associated with HER2 and c-Myc expression and with reduced disease-free
      survival. In this study, SRC-1(-/-) mice were backcrossed with FVB mice and then
      cross-bred with MMTV-polyoma middle T antigen (PyMT) mice to investigate the role
      of SRC-1 in breast cancer. Although mammary tumor initiation and growth were
      similar in SRC-1(-/-)/PyMT and wild-type (WT)/PyMT mice, genetic ablation of SRC
      1 antagonized PyMT-induced restriction of mammary ductal differentiation and
      elongation. SRC-1(-/-)/PyMT mammary tumors were also more differentiated than
      WT/PyMT mammary tumors. The intravasation of mammary tumor cells and the
      frequency and extent of lung metastasis were drastically reduced in SRC-1(-/
      )/PyMT mice compared with WT/PyMT mice. Metastatic analysis of transplanted
      WT/PyMT and SRC-1(-/-)/PyMT tumors in SRC-1(-/-) and WT recipient mice revealed
      that SRC-1 played an intrinsic role in tumor cell metastasis. Furthermore, SRC-1
      was up-regulated during mammary tumor progression. Disruption of SRC-1 inhibited
      Ets-2-mediated HER2 expression and PyMT-stimulated Akt activation in the mammary
      tumors. Disruption of SRC-1 also suppressed colony-stimulating factor-1 (CSF-1)
      expression and reduced macrophage recruitment to the tumor site. These results
      suggest that SRC-1 specifically promotes metastasis without affecting primary
      tumor growth. SRC-1 may promote metastasis through mediating Ets-2-mediated HER2
      expression and activating CSF-1 expression for macrophage recruitment. Therefore,
      functional interventions for coactivators like SRC-1 may provide unique
      approaches to control breast cancer progression and metastasis.

PMID- 19109435
TI  - Mapping RNA exit channel on transcribing RNA polymerase II by FRET analysis.
AB  - A simple genetic tag-based labeling method that permits specific attachment of a
      fluorescence probe near the C terminus of virtually any subunit of a protein
      complex is implemented. Its immediate application to yeast RNA polymerase II (pol
      II) enables us to test various hypotheses of RNA exit channel by using
      fluorescence resonance energy transfer (FRET) analysis. The donor dye is labeled
      on a site near subunit Rpb3 or Rpb4, and the acceptor dye is attached to the 5'
      end of RNA transcript in the pol II elongation complex. Both in-gel and single
      molecule FRET analysis show that the growing RNA is leading toward Rpb4, not
      Rpb3, supporting the notion that RNA exits through the proposed channel 1.
      Distance constraints derived from our FRET results, in conjunction with
      triangulation, reveal the exit track of RNA transcript on core pol II by
      identifying amino acids in the vicinity of the 5' end of RNA and show that the
      extending RNA forms contacts with the Rpb7 subunit. The significance of RNA exit
      route in promoter escape and that in cotranscriptional mRNA processing is
      discussed.

PMID- 19109436
TI  - Efficient colonic mucosal wound repair requires Trem2 signaling.
AB  - The colonic epithelial lining undergoes constant replacement, driven by
      epithelial stem cells in crypts of Lieberkuhn. Stem cells lost because of damage
      or disease can be replaced by adjacent crypts that undergo fission. The close
      proximity of an extraordinary number of luminal microbes creates a challenge for
      this repair process; infection must be prevented while immune system activation
      and epithelial stem cell genetic damage must be minimized. To understand the
      factors that modulate crypt/stem cell replacement in the mouse colon, we
      developed an in vivo acute injury system analogous to punch biopsy of the skin.
      In contrast to epidermal stem cells, colonic epithelial progenitors did not
      migrate over the wound bed. Instead, their proliferative expansion was confined
      to crypts adjacent to wound beds and was delayed to the latter phase of healing.
      This increased epithelial proliferation was coincident with the infiltration of
      Trem2 expressing macrophages and increased expression of IL-4 and IL-13 in the
      wound bed. Interestingly, Trem2(-/-) mice displayed slow and incomplete wound
      healing of colonic mucosal injuries. We found the latter phase of healing in
      Trem2(-/-) mice showed a diminished burst of epithelial proliferation, increased
      expression of IFN-gamma and TNF-alpha, diminished expression of IL-4 and IL-13,
      and increased markers of classical macrophage activation. Ablation of these
      cytokines in injured WT and Trem2(-/-) mice demonstrated that their expression
      ultimately determined the rate and nature of wound healing. These studies show
      that Trem2 signaling is an important pathway to promote healing of wounds in the
      colon where stem cell replacement is necessary.

PMID- 19109437
TI  - A conserved protonation-dependent switch controls drug binding in the Abl kinase.
AB  - In many protein kinases, a characteristic conformational change (the "DFG flip")
      connects catalytically active and inactive conformations. Many kinase inhibitors-
      including the cancer drug imatinib--selectively target a specific DFG
      conformation, but the function and mechanism of the flip remain unclear. Using
      long molecular dynamics simulations of the Abl kinase, we visualized the DFG flip
      in atomic-level detail and formulated an energetic model predicting that
      protonation of the DFG aspartate controls the flip. Consistent with our model's
      predictions, we demonstrated experimentally that the kinetics of imatinib binding
      to Abl kinase have a pH dependence that disappears when the DFG aspartate is
      mutated. Our model suggests a possible explanation for the high degree of
      conservation of the DFG motif: that the flip, modulated by electrostatic changes
      inherent to the catalytic cycle, allows the kinase to access flexible
      conformations facilitating nucleotide binding and release.

PMID- 19109438
TI  - Essential functions of the Williams-Beuren syndrome-associated TFII-I genes in
      embryonic development.
AB  - GTF2I and GTF2IRD1 encoding the multifunctional transcription factors TFII-I and
      BEN are clustered at the 7q11.23 region hemizygously deleted in Williams-Beuren
      syndrome (WBS), a complex multisystemic neurodevelopmental disorder. Although the
      biochemical properties of TFII-I family transcription factors have been studied
      in depth, little is known about the specialized contributions of these factors in
      pathways required for proper embryonic development. Here, we show that homozygous
      loss of either Gtf2ird1 or Gtf2i function results in multiple phenotypic
      manifestations, including embryonic lethality; brain hemorrhage; and
      vasculogenic, craniofacial, and neural tube defects in mice. Further analyses
      suggest that embryonic lethality may be attributable to defects in yolk sac
      vasculogenesis and angiogenesis. Microarray data indicate that the Gtf2ird1
      homozygous phenotype is mainly caused by an impairment of the genes involved in
      the TGFbetaRII/Alk1/Smad5 signal transduction pathway. The effect of Gtf2i
      inactivation on this pathway is less prominent, but downregulation of the
      endothelial growth factor receptor-2 gene, resulting in the deterioration of
      vascular signaling, most likely exacerbates the severity of the Gtf2i mutant
      phenotype. A subset of Gtf2ird1 and Gtf2i heterozygotes displayed microcephaly,
      retarded growth, and skeletal and craniofacial defects, therefore showing that
      haploinsufficiency of TFII-I proteins causes various developmental anomalies that
      are often associated with WBS.

PMID- 19109439
TI  - A role for the host coatomer and KDEL receptor in early vaccinia biogenesis.
AB  - Members of the poxvirus family have been investigated for their applications as
      vaccines and expression vectors and, more recently, because of concern for their
      potential as biological weapons. Vaccinia virus, the prototypic member, evolves
      through multiple forms during its replication. Here, we show a surprising way by
      which vaccinia hijacks coatomer for early viral biogenesis. Whereas coatomer
      forms COPI vesicles in the host early secretory system, vaccinia formation
      bypasses this role of coatomer, but instead, depends on coatomer interacting with
      the host KDEL receptor. To gain insight into the viral roles of these two host
      proteins, we have detected them on the earliest recognized viral forms. These
      findings not only suggest insights into early vaccinia biogenesis but also reveal
      an alternate mechanism by which coatomer acts.

PMID- 19109440
TI  - Nonlinear threshold behavior during the loss of Arctic sea ice.
AB  - In light of the rapid recent retreat of Arctic sea ice, a number of studies have
      discussed the possibility of a critical threshold (or "tipping point") beyond
      which the ice-albedo feedback causes the ice cover to melt away in an
      irreversible process. The focus has typically been centered on the annual minimum
      (September) ice cover, which is often seen as particularly susceptible to
      destabilization by the ice-albedo feedback. Here, we examine the central physical
      processes associated with the transition from ice-covered to ice-free Arctic
      Ocean conditions. We show that although the ice-albedo feedback promotes the
      existence of multiple ice-cover states, the stabilizing thermodynamic effects of
      sea ice mitigate this when the Arctic Ocean is ice covered during a sufficiently
      large fraction of the year. These results suggest that critical threshold
      behavior is unlikely during the approach from current perennial sea-ice
      conditions to seasonally ice-free conditions. In a further warmed climate,
      however, we find that a critical threshold associated with the sudden loss of the
      remaining wintertime-only sea ice cover may be likely.

PMID- 19109441
TI  - Accurate SHAPE-directed RNA structure determination.
AB  - Almost all RNAs can fold to form extensive base-paired secondary structures. Many
      of these structures then modulate numerous fundamental elements of gene
      expression. Deducing these structure-function relationships requires that it be
      possible to predict RNA secondary structures accurately. However, RNA secondary
      structure prediction for large RNAs, such that a single predicted structure for a
      single sequence reliably represents the correct structure, has remained an
      unsolved problem. Here, we demonstrate that quantitative, nucleotide-resolution
      information from a SHAPE experiment can be interpreted as a pseudo-free energy
      change term and used to determine RNA secondary structure with high accuracy.
      Free energy minimization, by using SHAPE pseudo-free energies, in conjunction
      with nearest neighbor parameters, predicts the secondary structure of
      deproteinized Escherichia coli 16S rRNA (>1,300 nt) and a set of smaller RNAs (75
      155 nt) with accuracies of up to 96-100%, which are comparable to the best
      accuracies achievable by comparative sequence analysis.

PMID- 19109442
TI  - Exposure to hydrogen peroxide and eye and nose symptoms among workers in a
      beverage processing plant.
AB  - OBJECTIVES: Two cross-sectional studies were undertaken on workers in a beverage
      processing plant to investigate the association between low H(2)O(2) exposure and
      symptoms of irritation (2005 study) and to investigate the effect of wearing
      respiratory protection (2006 study). METHODS: The study comprised 69 workers
      exposed to H(2)O(2) in sterile chambers and 65 unexposed controls. The exposure
      was assessed from measurements and work task information from employment records.
      The severity of work-related symptoms was evaluated using questionnaires. Data
      were analyzed by the Student's t-test, multiple linear regression and analysis of
      variance for repeated measures of symptoms. RESULTS: Symptoms of eye, nose and
      throat irritation were significantly (P < 0.001) more severe among exposed
      workers compared to controls. Exposure values were occasionally above American
      Conference of Governmental Industrial Hygienists (ACGIH) threshold limit value
      time-weighted average (TLV-TWA) in the sterile chambers. The relationship between
      the severity of symptoms and the number of entrances in the chambers was
      significant (P < 0.0001) in 2005 but not in 2006, when respirators were used
      during work in the sterile chamber. No differences were found between exposed who
      entered a sterile chamber in 2005 but not in 2006 and exposed who entered a
      sterile chamber both in 2005 and 2006. This suggests that respirators provided an
      efficient protection and that the irritative effects of exposure to H(2)O(2) in
      2005 did not disappear after 1 year. CONCLUSIONS: The source of risk was exposure
      in the sterile chamber, even though the time of exposure was generally only
      approximately 30 min. To ensure complete worker protection, there is a need for a
      short-term exposure limit for H(2)O(2) in addition to the existing ACGIH TLV-TWA
      value.

PMID- 19109443
TI  - Early environmental predictors of the affective and interpersonal constructs of
      psychopathy.
AB  - Early childhood maltreatment (i.e., physical, sexual, emotional abuse) and
      caregiver disruptions are hypothesized to be instrumental in altering the
      neurobiology of the brain, particularly the amygdala, and contributing to the
      development of the affective deficits examined in individuals with psychopathy.
      Exposure to early untoward life events in models of rodent and nonhuman primates
      changes the neurobiology of the stress response. It is hypothesized that these
      changes may permanently shape brain regions that mediate stress and emotion and
      therefore play a role in the etiology of affective disorders in humans. The
      significance of experience (e.g., the intensity/severity, chronicity/duration,
      and developmental timing of experiences) and how the accompanying changes in the
      activity of the hypothalamic-pituitary-adrenocortical system affect alterations
      in the amygdala are discussed as critical contributors to the etiology of
      psychopathy. A model is proposed in which early maltreatment experiences
      contribute to alterations to the amygdala and produce a blunted or dissociative
      response to stress, a key factor in the affective deficits observed in
      psychopaths.

PMID- 19109444
TI  - Effects of conventional physical therapy and functional strength training on
      upper limb motor recovery after stroke: a randomized phase II study.
AB  - BACKGROUND: Functional training and muscle strength training may improve upper
      limb motor recovery after stroke. Combining these as functional strength training
      (FST) might enhance the benefit, but it is unclear whether this is better than
      conventional physical therapy (CPT). Comparing FST with CPT is not
      straightforward. OBJECTIVE: This study aimed at assessing the feasibility of
      conducting a phase III trial comparing CPT with FST for upper limb recovery.
      METHODS: Randomized, observer-blind, phase II trial. Subjects had upper limb
      weakness within 3 months of anterior circulation infarction. Subjects were
      randomized to CPT (no extra therapy), CPT + CPT, and CPT + FST. Intervention
      lasted 6 weeks. Primary outcome measure was the Action Research Arm Test (ARAT).
      Measurements were taken before treatment began, after 6 weeks of intervention,
      and 12 weeks thereafter. Attrition rate was calculated and differences between
      groups were interpreted using descriptive statistics. ARAT data were used to
      inform a power calculation. RESULTS: Thirty subjects were recruited (8% of people
      screened). Attrition rate was 6.7% at outcome and 40% at follow-up. At outcome
      the CPT + FST group showed the largest increase in ARAT score and this was above
      the clinically important level of 5.7 points. Median (interquartile range)
      increases were 11.5 (21.0) for CPT; 8.0 (13.3) for CPT + CPT; and 19.5 (22.0) for
      CPT + FST. The estimated sample size for an adequately powered subsequent phase
      III trial was 279 subjects at outcome. CONCLUSION: Further work toward a phase
      III clinical trial appears justifiable.

PMID- 19109445
TI  - Transcutaneously coupled, high-frequency electrical stimulation of the pudendal
      nerve blocks external urethral sphincter contractions.
AB  - BACKGROUND: Detrusor-sphincter dyssynergia is a condition in which reflexive
      contractions of the external urethral sphincter occur during bladder
      contractions, preventing the expulsion of urine. High-frequency stimulation (kHz
      range) has been shown to elicit a fast-acting and reversible block of action
      potential propagation in peripheral nerves, which may be a useful technique in
      the management of this condition. OBJECTIVE: The aim of these experiments was to
      see if a newly developed stimulus delivery system, capable of transmitting
      current transcutaneously to remote peripheral nerves using a passive implanted
      conductor, was an effective way to transmit high-frequency waveforms to the
      pudendal nerve to block ongoing sphincter contractions. METHODS: High-frequency
      waveforms were delivered through the skin to the pudendal nerve using a passive
      implanted conductor in 6 adult cats anesthetized with isoflurane. Five of the
      experiments were acute, terminal procedures, and the remaining cat was implanted
      with a permanent electrode system allowing evaluation for 6 months. Typical
      stimulation parameters were in the range of 1 to 10 kHz and 1 to 10 mA. RESULTS:
      Complete blocking of external urethral sphincter contractions was achieved in 5
      of the 6 animals. High-frequency stimulation was also tested in the chronically
      implanted animal without anesthesia, and the stimulation was tolerated with
      minimal aversive reactions. CONCLUSIONS: The transcutaneous passive implanted
      conductor stimulus delivery system is an effective way to stimulate the pudendal
      nerve at high frequency, leading to sphincter relaxation. This system may provide
      a simple means to implement this stimulation paradigm in people with detrusor
      sphincter dyssynergia.

PMID- 19109447
TI  - Multicenter randomized clinical trial evaluating the effectiveness of the Lokomat
      in subacute stroke.
AB  - OBJECTIVE: To compare the efficacy of robotic-assisted gait training with the
      Lokomat to conventional gait training in individuals with subacute stroke.
      METHODS: A total of 63 participants<6 months poststroke with an initial walking
      speed between 0.1 to 0.6 m/s completed the multicenter, randomized clinical
      trial. All participants received twenty-four 1-hour sessions of either Lokomat or
      conventional gait training. Outcome measures were evaluated prior to training,
      after 12 and 24 sessions, and at a 3-month follow-up exam. Self-selected
      overground walking speed and distance walked in 6 minutes were the primary
      outcome measures, whereas secondary outcome measures included balance, mobility
      and function, cadence and symmetry, level of disability, and quality of life
      measures. RESULTS: Participants who received conventional gait training
      experienced significantly greater gains in walking speed (P=.002) and distance
      (P=.03) than those trained on the Lokomat. These differences were maintained at
      the 3-month follow-up evaluation. Secondary measures were not different between
      the 2 groups, although a 2-fold greater improvement in cadence was observed in
      the conventional versus Lokomat group. CONCLUSIONS: For subacute stroke
      participants with moderate to severe gait impairments, the diversity of
      conventional gait training interventions appears to be more effective than
      robotic-assisted gait training for facilitating returns in walking ability.

PMID- 19109448
TI  - Characterization of reference materials for human antiserum to pertussis antigens
      by an international collaborative study.
AB  - Enzyme-linked immunosorbent assay (ELISA) has been widely used to evaluate
      antibody responses to pertussis vaccination and infection. A common reference
      serum is essential for the standardization of these assays. However, no
      internationally recognized reference serum is available. At the request of the
      Expert Committee on Biological Standardization (ECBS) of the World Health
      Organization (WHO), a set of four candidate international standards has been
      prepared. These candidate materials have been assessed for suitability and
      compared to the widely used U.S. reference pertussis antiserum (human) lot 3, lot
      4, and lot 5 by 22 laboratories from 15 countries in an international
      collaborative study. Laboratories measured immunoglobulin G (IgG) and IgA
      antibodies to pertussis toxin (PT), filamentous hemagglutinin (FHA), pertactin
      (PRN), and fimbriae (Fim2&3) using their established immunoassays. The results of
      this study showed each of the four candidates to be suitable as an international
      standard. With the agreement of the participants, a recommendation has been made
      to the ECBS that the candidate material coded 06/140 be established as the First
      International Standard for pertussis antiserum (human), with the following
      assigned international units (IU): IgG anti-PT, 335 IU/ampoule; IgA anti-PT, 65
      IU/ampoule; IgG anti-FHA, 130 IU/ampoule; IgA anti-FHA, 65 IU/ampoule; IgG anti
      PRN, 65 IU/ampoule; and IgA anti-PRN, 42 IU/ampoule. No formal units have been
      proposed for anti-Fim2&3 because most assays used a mixture of fimbrial antigens.
      In addition, the candidate material coded 06/142 has been proposed as a WHO
      working preparation for characterization of assay systems.

PMID- 19109449
TI  - Streptococcus suis bacterin and subunit vaccine immunogenicities and protective
      efficacies against serotypes 2 and 9.
AB  - Streptococcus suis causes numerous diseases in pigs, most importantly,
      meningitis, arthritis, septicemia, and bronchopneumonia. One of the major
      problems in modern swine production is the lack of a vaccine protecting against
      more than one S. suis serotype. The objective of this study was to determine the
      protective efficacy of a serotype 2 murein-associated protein (MAP) fraction
      subunit vaccine in comparison to that of a bacterin against experimental
      challenge with serotype 2 (containing muramidase-released protein [MRP],
      extracellular factor, and suilysin [SLY]) and serotype 9 (containing MRP variant
      MRP* and SLY) strains. MAP was shown to include different surface-associated
      proteins, such as the MRP and surface antigen one (SAO) expressed by both
      pathotypes used for challenge. The results of this study demonstrated that the
      serotype 2 bacterin induced protective immunity against homologous challenge. In
      contrast, the protective efficacy of the MAP subunit vaccine was low, though MAP
      immunization resulted in high serum immunoglobulin G2 titers against MRP and SAO.
      Importantly, immunization with bacterin but not with MAP induced opsonizing
      antibody titers against the serotype 2 strain, and these antibody titers were
      found to correlate with protection. However, after absorption with a
      nonencapsulated isogenic mutant, the sera from bacterin-immunized piglets failed
      to facilitate neutrophil killing, indicating that antibodies directed against
      capsule may not have been essential for opsonophagocytosis. Furthermore,
      induction of opsonizing antibodies against serotype 9 was not detectable in the
      group receiving bacterin or in the group receiving the MAP vaccine. In agreement,
      protection against the heterologous serotype 9 strain was low in both groups.
      Thus, identification of an antigen protecting against these two important S. suis
      pathotypes remains an important goal of future studies.

PMID- 19109450
TI  - Foal monocyte-derived dendritic cells become activated upon Rhodococcus equi
      infection.
AB  - Susceptibility of foals to Rhodococcus equi pneumonia is exclusive to the first
      few months of life. The objective of this study was to investigate the immediate
      immunologic response of foal and adult horse antigen-presenting cells (APCs) upon
      infection with R. equi. We measured the activation of the antigen-presenting
      major histocompatibility complex (MHC) class II molecule, costimulatory molecules
      CD40 and CD86, the cytokine interleukin-12 (IL-12), and the transcriptional
      factor interferon regulatory factor 1 (IRF-1) in monocyte-derived macrophages
      (mMOs) and dendritic cells (mDCs) of adult horses and foals of different ages
      (from birth to 3 months of age) infected with virulent R. equi or its avirulent,
      plasmid-cured derivative. Infection with virulent or avirulent R. equi induced (P
      <or= 0.01) the expression of IL-12p35 and IL-12p40 mRNAs in foal mMOs and mDCs at
      different ages. This response was likely mediated by the higher (P=0.008)
      expression of IRF-1 in foal mDCs at birth than in adult horse mDCs. R. equi
      infection promoted comparable expression of costimulatory molecules CD86 and CD40
      in foal and adult horse cells. The cytokine and costimulatory response by foal
      mDCs was not accompanied by robust MHC class II molecule expression. These data
      suggest that foal APCs detect the presence of R. equi and respond with the
      expression of the Th1-inducing cytokine IL-12. Nevertheless, there seems to be a
      limitation to MHC class II molecule expression which we hypothesize may
      compromise the efficient priming of naive effector cells in early life.

PMID- 19109451
TI  - Meningococcal outer membrane vesicle vaccines derived from mutant strains
      engineered to express factor H binding proteins from antigenic variant groups 1
      and 2.
AB  - Meningococcal outer membrane vesicle (OMV) vaccines, which are treated with
      detergents to decrease endotoxin activity, are safe and effective in humans.
      However, the vaccines elicit serum bactericidal antibody responses largely
      directed against PorA, which is antigenically variable. We previously prepared a
      native (non-detergent-treated) OMV vaccine from a mutant of group B strain H44/76
      in which the lpxL1 gene was inactivated, which resulted in penta-acylated lipid A
      with attenuated endotoxin activity. To enhance protection, we overexpressed
      factor H binding protein (fHbp) from the antigenic variant 1 group. The vaccine
      elicited broad serum bactericidal antibody responses in mice against strains with
      fHbp variant 1 (approximately 70% of group B isolates) but not against strains
      with variant 2 or 3. In the present study, we constructed a mutant of group B
      strain NZ98/254 with attenuated endotoxin that expressed both endogenous variant
      1 and heterologous fHbp variant 2. A mixture of the two native OMV vaccines from
      the H44/76 and NZ98/254 mutants stimulated proinflammatory cytokine responses by
      human peripheral blood mononuclear cells similar to those stimulated by control,
      detergent-treated OMV vaccines from the wild-type strains. In mice, the mixture
      of the two native OMV vaccines elicited broad serum bactericidal antibody
      responses against strains with heterologous PorA and fHbp in the variant 1, 2, or
      3 group. By adsorption studies, the principal bactericidal antibody target was
      determined to be fHbp. Thus, native OMV vaccines from mutants expressing fHbp
      variants have the potential to be safe for humans and to confer broad protection
      against meningococcal disease from strains expressing fHbp from each of the
      antigenic variant groups.

PMID- 19109452
TI  - Prediction of subjective affective state from brain activations.
AB  - Decoding and information theoretic techniques were used to analyze the
      predictions that can be made from functional magnetic resonance neuroimaging data
      on individual trials. The subjective pleasantness produced by warm and cold
      applied to the hand could be predicted on single trials with typically in the
      range 60-80% correct from the activations of groups of voxels in the
      orbitofrontal and medial prefrontal cortex and pregenual cingulate cortex, and
      the information available was typically in the range 0.1-0.2 (with a maximum of
      0.6) bits. The prediction was typically a little better with multiple voxels than
      with one voxel, and the information increased sublinearly with the number of
      voxels up to typically seven voxels. Thus the information from different voxels
      was not independent, and there was considerable redundancy across voxels. This
      redundancy was present even when the voxels were from different brain areas. The
      pairwise stimulus-dependent correlations between voxels, reflecting higher-order
      interactions, did not encode significant information. For comparison, the
      activity of a single neuron in the orbitofrontal cortex can predict with 90%
      correct and encode 0.5 bits of information about whether an affectively positive
      or negative visual stimulus has been shown, and the information encoded by small
      numbers of neurons is typically independent. In contrast, the activation of a 3 x
      3 x 3-mm voxel reflects the activity of approximately 0.8 million neurons or
      their synaptic inputs and is not part of the information encoding used by the
      brain, thus providing a relatively poor readout of information compared with that
      available from small populations of neurons.

PMID- 19109453
TI  - Using a common average reference to improve cortical neuron recordings from
      microelectrode arrays.
AB  - In this study, we propose and evaluate a technique known as common average
      referencing (CAR) to generate a more ideal reference electrode for microelectrode
      recordings. CAR is a computationally simple technique, and therefore amenable to
      both on-chip and real-time applications. CAR is commonly used in EEG, where it is
      necessary to identify small signal sources in very noisy recordings. To study the
      efficacy of common average referencing, we compared CAR to both referencing with
      a stainless steel bone-screw and a single microelectrode site. Data consisted of
      in vivo chronic recordings in anesthetized Sprague-Dawley rats drawn from prior
      studies, as well as previously unpublished data. By combining the data from
      multiple studies, we generated and analyzed one of the more comprehensive chronic
      neural recording datasets to date. Reference types were compared in terms of
      noise level, signal-to-noise ratio, and number of neurons recorded across days.
      Common average referencing was found to drastically outperform standard types of
      electrical referencing, reducing noise by >30%. As a result of the reduced noise
      floor, arrays referenced to a CAR yielded almost 60% more discernible neural
      units than traditional methods of electrical referencing. CAR should impart
      similar benefits to other microelectrode recording technologies-for example,
      chemical sensing-where similar differential recording concepts apply. In
      addition, we provide a mathematical justification for CAR using Gauss-Markov
      theorem and therefore help place the application of CAR into a theoretical
      context.

PMID- 19109455
TI  - Near optimal combination of sensory and motor uncertainty in time during a
      naturalistic perception-action task.
AB  - Most behavioral tasks have time constraints for successful completion, such as
      catching a ball in flight. Many of these tasks require trading off the time
      allocated to perception and action, especially when only one of the two is
      possible at any time. In general, the longer we perceive, the smaller the
      uncertainty in perceptual estimates. However, a longer perception phase leaves
      less time for action, which results in less precise movements. Here we examine
      subjects catching a virtual ball. Critically, as soon as subjects began to move,
      the ball became invisible. We study how subjects trade-off sensory and movement
      uncertainty by deciding when to initiate their actions. We formulate this task in
      a probabilistic framework and show that subjects' decisions when to start moving
      are statistically near optimal given their individual sensory and motor
      uncertainties. Moreover, we accurately predict individual subject's task
      performance. Thus we show that subjects in a natural task are quantitatively
      aware of how sensory and motor variability depend on time and act so as to
      minimize overall task variability.

PMID- 19109456
TI  - Surround suppression of V1 neurons mediates orientation-based representation of
      high-order visual features.
AB  - Neurons with surround suppression have been implicated in processing high-order
      visual features such as contrast- or texture-defined boundaries and subjective
      contours. However, little is known regarding how these neurons encode high-order
      visual information in a systematic manner as a population. To address this issue,
      we have measured detailed spatial structures of classical center and suppressive
      surround regions of receptive fields of primary visual cortex (V1) neurons and
      examined how a population of such neurons allow encoding of various high-order
      features and shapes in visual scenes. Using a novel method to reconstruct
      structures, we found that the center and surround regions are often both
      elongated parallel to each other, reminiscent of on and off subregions of simple
      cells without surround suppression. These structures allow V1 neurons to extract
      high-order contours of various orientations and spatial frequencies, with a
      variety of optimal values across neurons. The results show that a wide range of
      orientations and widths of the high-order features are systematically represented
      by the population of V1 neurons with surround suppression.

PMID- 19109454
TI  - Temporal precision of neuronal information in a rapid perceptual judgment.
AB  - In many situations, such as pedestrians crossing a busy street or prey evading
      predators, rapid decisions based on limited perceptual information are critical
      for survival. The brevity of these perceptual judgments constrains how neuronal
      signals are integrated or pooled over time because the underlying sequence of
      processes, from sensation to perceptual evaluation to motor planning and
      execution, all occur within several hundred milliseconds. Because most previous
      physiological studies of these processes have relied on tasks requiring
      considerably longer temporal integration, the neuronal basis of such rapid
      decisions remains largely unexplored. In this study, we examine the temporal
      precision of neuronal activity associated with a rapid perceptual judgment. We
      find that the activity of individual neurons over tens of milliseconds can
      reliably convey information about sensory events and was well correlated with the
      animals' judgments. There was a strong correlation between sensory reliability
      and the correlation with behavioral choice, suggesting that rapid decisions were
      preferentially based on the most reliable sensory signals. We also find that a
      simple model in which the responses of a small number of individual neurons (<5)
      are summed can completely explain behavioral performance. These results suggest
      that neuronal circuits are sufficiently precise to allow for cognitive decisions
      to be based on small numbers of action potentials from highly reliable neurons.

PMID- 19109458
TI  - Mechanisms of group I mGluR-dependent long-term depression of NMDA receptor
      mediated transmission at Schaffer collateral-CA1 synapses.
AB  - The mechanisms underlying group I metabotropic glutamate receptor (mGluR)
      dependent long-term depression (LTD) of N-methyl-d-aspartate receptor (NMDAR)
      mediated synaptic currents (EPSCs(NMDAR)) are poorly understood. Here we
      investigated the effects of (R,S)-3,5-dihydroxyphenylglycine (DHPG), a selective
      agonist of group I mGluRs, on the EPSCs(NMDAR) in area CA1 of acute hippocampal
      slices from 6- to 8-wk Sprague-Dawley rats. DHPG acutely and persistently
      depressed the isolated EPSC(NMDAR) and transiently slowed its decay rate.
      Combined antagonism of mGluR1 and mGluR5 blocked the effects of DHPG. Strong
      calcium buffering with intracellular BAPTA did not reduce the acute depression or
      LTD, making the involvement of elevated postsynaptic calcium unlikely. The acute
      depression and LTD were not mediated by activation of tyrosine kinases or
      phosphatases, nor were they dependent on protein synthesis. However, the LTD was
      prevented by the intracellular actin-stabilizer jasplakinolide, raising the
      possibility that it was associated with a lateral movement of NMDARs. Supporting
      this hypothesis, when the effective spatial spread of synaptically released
      glutamate was increased using the glutamate transporter inhibitor TBOA, the
      resultant EPSC(NMDAR) did not undergo LTD in response to DHPG. Importantly,
      isolation of the extrasynaptic EPSC(NMDAR) by blockade of synaptic NMDARs with MK
      801 showed that this was not due to a potentiation of the preexisting
      extrasynaptic component. These findings indicate that LTD of NMDAR-mediated
      synaptic transmission occurs via lateral movement of receptors away from the
      synapse.

PMID- 19109457
TI  - Whisking in air: encoding of kinematics by trigeminal ganglion neurons in awake
      rats.
AB  - Active sensing requires the brain to distinguish signals produced by external
      inputs from those generated by the animal's own movements. Because the rodent
      whisker musculature lacks proprioceptors, we asked whether trigeminal ganglion
      neurons encode the kinematics of the rat's own whisker movements in air. By
      examining the role of kinematics, we have extended previous findings showing that
      many neurons that respond during such movements do not do so consistently.
      Nevertheless, the majority ( approximately 70%) of trigeminal ganglion neurons
      display significant correlations between firing rate and a kinematic parameter,
      and a subset, approximately 30%, represent kinematics with high reliability.
      Preferential firing to movement direction was observed but was strongly modulated
      by movement amplitude and speed. However, in contrast to the precise time-locking
      that occurs in response to active whisker contacts, whisker movements in air
      generate temporally dispersed responses that are not time-locked to the onset of
      either protractions or retractions.

PMID- 19109459
TI  - Discrete parieto-frontal functional connectivity related to grasping.
AB  - The human inferior parietal lobule (IPL) is known to have neuronal connections
      with the frontal lobe, and these connections have been shown to be associated
      with sensorimotor integration to perform various types of movement such as
      grasping. The function of these anatomical connections has not been fully
      investigated. We studied the judgment of graspability of objects in an event
      related functional MRI study in healthy subjects, and found activation in two
      different regions within IPL: one in the left dorsal IPL extending to the
      intraparietal sulcus and the other in the left ventral IPL. The former region was
      activated only in the judgment of graspable objects, whereas the latter was
      activated in the judgment of both graspable and nongraspable objects although the
      activation was greater for the graspable objects. Psychophysiological interaction
      analysis showed that these regions had similar but discrete functional
      connectivity to the lateral and medial frontal cortices. In relation to this
      particular task, the left dorsal IPL had functional connectivity to the left
      ventral premotor cortex, supplementary motor area (SMA) and right cerebellar
      cortex, whereas the left ventral IPL had functional connectivity to the left
      dorsolateral prefrontal cortex and pre-SMA. These findings suggest that the
      connection from the left dorsal IPL is associated specifically with automatic
      flow of information about grasping behavior. By contrast, the connection from the
      left ventral IPL might be related to motor imagination or enhanced external
      attention to the presented stimuli.

PMID- 19109460
TI  - Utilization of microsatellite polymorphism for differentiating herpes simplex
      virus type 1 strains.
AB  - The herpes simplex virus type 1 (HSV-1) genome is a linear double-stranded DNA of
      152 kpb. It is divided into long and short regions of unique sequences termed
      U(L) and U(S), respectively, and these are flanked by regions of inverted
      internal and terminal repeats. Microsatellites are short tandem repeats of 1- to
      6-nucleotide motifs; they are often highly variable and polymorphic within the
      genome, which raises the question of whether they may be used as molecular
      markers for the precise differentiation of HSV-1 strains. In this study, 79
      different microsatellites (mono-, di-, and trinucleotide repeats) in the HSV-1
      complete genome were identified by in silico analysis. Among those
      microsatellites, 45 were found to be distributed in intergenic or noncoding
      inverted repeat regions, while 34 were in open reading frames. Length
      polymorphism analysis of the PCR products was used to investigate a set of 12
      distinct HSV-1 strains and allowed the identification of 23 polymorphic and 6
      monomorphic microsatellites, including two polymorphic trinucleotide repeats (CGT
      and GGA) within the UL46 and US4 genes, respectively. A multiplex PCR method that
      amplified 10 polymorphic microsatellites was then developed for the rapid and
      accurate genetic characterization of HSV-1 strains. Each HSV-1 strain was
      characterized by its own microsatellite haplotype, which proved to be stable over
      time in cell culture. This relevant innovative tool was successfully applied both
      to confirm the close relationship between sequential HSV-1 isolates collected
      from patients with multiple recurrent infections and to investigate putative
      nosocomial infections.

PMID- 19109461
TI  - Epidemiological screening for hepatitis E virus in bile specimens from livestock
      in northwest China.
AB  - Hepatitis E has been hypothesized as a zoonosis. However, there is no definite
      conclusion about which animal species contribute to hepatitis E virus (HEV)
      infection in humans. In this study, HEV RNA was detected only in swine bile
      specimens and not in bile specimens collected from cattle, goats, or dogs. We
      postulate that swine are the main animal reservoir for HEV.

PMID- 19109462
TI  - Optical fingerprinting in bacterial epidemiology: Raman spectroscopy as a real
      time typing method.
AB  - Hospital-acquired infections (HAI) increase morbidity and mortality and
      constitute a high financial burden on health care systems. An effective weapon
      against HAI is early detection of potential outbreaks and sources of
      contamination. Such monitoring requires microbial typing with sufficient
      reproducibility and discriminatory power. Here, a microbial-typing method is
      presented, based on Raman spectroscopy. This technique provides strain-specific
      optical fingerprints in a few minutes instead of several hours to days, as is the
      case with genotyping methods. Although the method is generally applicable, we
      used 118 Staphylococcus aureus isolates to illustrate that the discriminatory
      power matches that of established genotyping techniques (numerical index of
      diversity [D]=0.989) and that concordance with the gold standard (pulsed-field
      gel electrophoresis) is high (95%). The Raman clustering of isolates was
      reproducible to the strain level for five independent cultures, despite the
      various culture times from 18 h to 24 h. Furthermore, this technique was able to
      classify stored (-80 degrees C) and recent isolates of a methicillin-resistant
      Staphylococcus aureus-colonized individual during surveillance studies and did so
      days earlier than established genotyping techniques did. Its high throughput and
      ease of use make it suitable for use in routine diagnostic laboratory settings.
      This will set the stage for continuous, automated, real-time epidemiological
      monitoring of bacterial infections in a hospital, which can then be followed by
      timely corrective action by infection prevention teams.

PMID- 19109463
TI  - Comparative molecular analysis substantiates zoonotic potential of equine
      methicillin-resistant Staphylococcus aureus.
AB  - Despite the increasing importance of methicillin-resistant Staphylococcus aureus
      (MRSA) in veterinary medicine, knowledge about the epidemiology of the pathogen
      in horses is still poor. The phylogenetic relationship of strains of human and
      equine origins has been addressed before, usually by analyzing results of common
      standard classification methods for MRSA. This work intends to go beyond the
      baseline of typing procedures in order to comparatively characterize equine and
      human MRSA strains with similar phylogenetic backgrounds. In addition to
      multilocus sequence typing, pulsed-field gel electrophoresis, spa typing,
      staphylococcal cassette chromosome mec typing, and a PCR for Panton-Valentine
      leukocidin gene detection, a microarray analysis of a total of 185 structural,
      virulence-associated, and resistance loci was applied. The results showed that
      clonal complex 8 (CC8) was absolutely predominant (16 strains) in 19 investigated
      equine MRSA strains. Of the CC8 strains, 13 belonged to sequence type 254 (ST254)
      and the other 3 to ST8. This genotype has been isolated from different equine
      patients in various regions over several years, substantiating the apparent
      predominance of CC8 STs in MRSA strains of horses worldwide. Furthermore,
      comparatively investigated human strains of ST254 displayed molecular-typing
      results indistinguishable from those for strains of equine origin. Two further
      equine strains (ST22 and ST1117) showed similarity to ST22 human strains (CC22).
      One equine strain belonged to ST398, a genotype recently described as being
      frequently isolated from specimens from pigs and pig farmers. These data provide
      evidence for the adaptation of certain MRSA genotypes to more than one mammalian
      species, reflecting their extended host spectra.

PMID- 19109464
TI  - Molecular epidemiology of norovirus gastroenteritis investigated using samples
      collected from children in Tunisia during a four-year period: detection of the
      norovirus variant GGII.4 Hunter as early as January 2003.
AB  - Human noroviruses (NoVs) cause epidemic and endemic acute gastroenteritis in
      children and adults. To study the prevalence and genetic diversity of NoV in
      children in Tunisia, a total of 788 fecal samples were collected during a 4-year
      period in the region of Monastir, from children 12 years of age or younger,
      hospitalized or presenting in dispensaries with symptoms of acute
      gastroenteritis. NoV was detected by reverse transcription-PCR and confirmed by
      sequence analysis. This is the first report that describes the molecular
      epidemiology of NoV in Tunisian children: NoVs were characterized as the
      causative agent in 128 (16.2%) of the samples. Fourteen samples contained a
      mixture of two NoVs, and 33 samples were coinfected with additional enteric
      viruses. Eight distinct NoV genotypes were detected (GGI.2, GGI.4, GGII.1,
      GGII.4, GGII.8, GGII.14, GGIIb/GGII.2, and GGIIb/GGII.3). GGII.4 was the most
      prevalent genotype, accounting for 83 (64.8%) cases. Interestingly the GGII.4
      variant Hunter, described as spreading all over the world in 2004, was found in
      Tunisia as early as January 2003. The delay of 1 year between the isolation in
      Tunisia and the worldwide emergence is somewhat surprising, considering the
      importance of the contacts between North Africa and Europe particularly.
      Nevertheless, this illustrates the idea that sporadic gastroenteritis cases may
      be a reservoir for emerging epidemic NoV strains.

PMID- 19109465
TI  - Isolation and characterization of a new fungal species, Chrysosporium
      ophiodiicola, from a mycotic granuloma of a black rat snake (Elaphe obsoleta
      obsoleta).
AB  - Isolation and characterization of the new species Chrysosporium ophiodiicola from
      a mycotic granuloma of a black rat snake (Elaphe obsoleta obsoleta) are reported.
      Analysis of the sequences of different fragments of the ribosomal genes
      demonstrated that this species belongs to the Onygenales and that this species is
      genetically different from other morphologically similar species of
      Chrysosporium. This new species is unique in having both narrow and cylindrical
      to-slightly clavate conidia and a strong, pungent odor.

PMID- 19109466
TI  - Outbreak of acute respiratory disease in China caused by B2 species of adenovirus
      type 11.
AB  - An outbreak of acute respiratory tract infection occurred in Shanxi Province,
      China, from March to April 2006. Of the 254 patients affected by this outbreak,
      247 patients were students of a senior high school; 1 of these patients died
      during the outbreak. Serological tests and blood culture revealed no evidence of
      bacterial infection. The results of direct reverse transcription-PCR or PCR
      performed with clinical specimens collected from the patients, including the sole
      patient who died, were positive for human adenoviruses (HAdVs) but negative for
      influenza virus, measles virus, rubella virus, mumps virus, parainfluenza virus,
      respiratory syncytial virus, and human enteroviruses. These findings were
      confirmed by enzyme-linked immunosorbent assay for HAdV immunoglobulin A, the
      conventional neutralization test, and viral isolation and identification.
      Sequencing of the entire hexon gene revealed that HdAV type 11a (HAdV-11a)
      belonging to the B2 species of HAdV was the etiological agent responsible for the
      outbreak. However, both the analysis of the phylogenetic relationship and the
      similarity plot indicated that the sequence of the 3' end of the hexon gene
      outside the hypervariable regions the HAdV-11a strain isolated in this outbreak
      may be a recombinant with the sequence of the HAdV-14 strain of species B2.
      Although isolates of HAdV species B2 seldom cause respiratory infections, they
      may pose a new global challenge with regard to acute respiratory diseases; this
      possibility cannot be overlooked and should be carefully considered. Hence, the
      need to establish and improve both epidemiological and virological surveillance
      of HAdV infections in China should be emphasized.

PMID- 19109467
TI  - Reversion of influenza A (H3N2) virus from amantadine resistant to amantadine
      sensitive by further reassortment in Japan during the 2006-to-2007 influenza
      season.
AB  - In the 2006-to-2007 influenza season, amantadine-sensitive strains were found
      among the N-lineage influenza A (H3N2) viruses, which were previously believed to
      be associated with amantadine resistance. Whole-genome sequencing results
      indicated that this was due to a further reassortment event.

PMID- 19109468
TI  - Population structure of human isolates of Streptococcus agalactiae from Dakar and
      Bangui.
AB  - Multilocus sequence types of 163 human Streptococcus agalactiae strains isolated
      in Bangui and Dakar were analyzed. We identified local specificities in the
      distribution of sequence types and capsular serotypes. However, the overall
      population structure is similar to that in the United States and Europe,
      suggesting that few specific clones colonize humans.

PMID- 19109469
TI  - Use of the BacT/Alert MB mycobacterial blood culture system for detection of
      mycobacteria in sterile body fluids other than blood.
AB  - The definitive diagnosis of extrapulmonary tuberculosis is made by a positive
      body fluid culture result. Conventional culture methods require centrifugation or
      filtration of body fluid (peritoneal, pleural, synovial, or pericardial fluid) in
      order to improve the sensitivity. The aim of the present study was to evaluate
      the feasibility of the direct inoculation, at the patient's bedside, of up to 5
      ml of uncentrifuged fluid onto BacT/Alert MB culture bottles (bioMerieux, Durham,
      NC).

PMID- 19109470
TI  - Unreliable extended-spectrum beta-lactamase detection in the presence of plasmid
      mediated AmpC in Escherichia coli clinical isolates.
AB  - The emergence of extended-spectrum beta-lactamase (ESBL) and plasmid-mediated
      AmpC (pAmpC) enzymes in Escherichia coli raises concern regarding accurate
      laboratory detection and interpretation of susceptibility testing results. Twenty
      six cefpodoxime ESBL screen-positive, cefoxitin-resistant E. coli clinical
      isolates were subjected to clavulanate ESBL confirmatory testing employing disk
      augmentation, Etest, and the BD Phoenix NMC/ID-132 panel. Phenotypic pAmpC
      production was assessed by boronic acid disk augmentation. ESBL and pAmpC genes
      were detected by gene amplification and sequencing. ESBL genes (SHV and/or CTX-M
      type genes) were detected in only 7/26 ESBL screen-positive isolates. Of 23
      aminophenylboronic acid screen-positive isolates, pAmpC genes were detected in 20
      (CMY-2 or FOX-5 genes). High incidences of false-positive ESBL confirmatory
      results were observed for both clavulanate disk augmentation (9/19) and BD
      Phoenix (5/19). All were associated with the presence of pAmpC genes with or
      without TEM-1. Etest performed poorly, as the majority of interpretations were
      nondeterminable. In addition, false-negative ESBL confirmatory results were
      observed in isolates possessing concomitant ESBL and pAmpC genes for Etest (four
      of five), BD Phoenix (three of five), and disk augmentation (one of five). The
      results indicate poor performance of currently employed ESBL confirmatory methods
      in the setting of concomitant pAmpC. Some isolates with pAmpC and ESBL genes fell
      within the susceptible category to extended-spectrum cephalosporins, raising
      concern over currently employed breakpoints.

PMID- 19109471
TI  - Development and evaluation of a real-time reverse transcription-loop-mediated
      isothermal amplification assay for rapid detection of Rift Valley fever virus in
      clinical specimens.
AB  - This paper reports on the development and validation of a real-time reverse
      transcription-loop-mediated isothermal amplification assay (RT-LAMP) targeting
      the genomic large RNA segment of Rift Valley fever virus (RVFV). The set of six
      designed RT-LAMP primers identified strains of RVFV isolated in geographically
      distinct areas over a period of 50 years; there was no cross-reactivity with
      other genetically related and unrelated arboviruses. When testing serial sera and
      plasma from sheep experimentally infected with wild-type RVFV, there was 100%
      agreement between results of the RT-LAMP, a TaqMan-based real-time PCR, and virus
      isolation. Similarly, the assay had very high levels of diagnostic sensitivity
      and specificity when testing various clinical specimens from humans and animals
      naturally infected with the virus during recent outbreaks of the disease in
      Africa. The detection of specific viral genome targets in positive clinical
      specimens was achieved in less than 30 min. As a highly accurate, rapid, and very
      simple nucleic acid detection format, the RT-LAMP has the potential to be used in
      less-well-equipped laboratories in Africa and as a portable device during RVF
      outbreaks in remote areas, and it can be a valuable tool for the differential
      diagnosis of viral hemorrhagic fevers.

PMID- 19109472
TI  - Infective endocarditis in a dog and the phylogenetic relationship of the
      associated "Bartonella rochalimae" strain with isolates from dogs, gray foxes,
      and a human.
AB  - The first case of canine endocarditis caused by "Bartonella rochalimae" is
      reported. By PCR-restriction fragment length polymorphism, sequence, and
      phylogenetic analyses, Bartonella isolates from a dog with endocarditis, 22 gray
      foxes, and three dogs, described as B. clarridgeiae like, were confirmed to
      belong to the new species "B. rochalimae," suggesting canids as the natural
      reservoir.

PMID- 19109473
TI  - Simple, sensitive, and swift sequencing of complete H5N1 avian influenza virus
      genomes.
AB  - The spread of highly pathogenic avian influenza A virus (HPAIV) of subtype H5N1
      demands fast and reliable methods for in-depth, full-length sequence analysis.
      For this purpose, we designed a simple and sensitive method for the preparation
      of sequencing libraries from H5N1 HPAIV diagnostic RNA samples for sequencing
      with the Genome Sequencer FLX instrument. The method presented seamlessly
      integrates high-throughput pyrosequencing with the Roche/454 instrument into
      diagnostics without the need for additional equipment or molecular biological
      techniques besides standard PCR and the Genome Sequencer FLX sample preparation
      and sequencing pipeline.

PMID- 19109474
TI  - Clinical predictive value of real-time PCR quantification of human
      cytomegalovirus DNA in amniotic fluid samples.
AB  - The aim of this study was to evaluate the diagnostic reliability and prognostic
      significance of the quantification of cytomegalovirus (CMV) DNA in amniotic fluid
      (AF). We retrospectively reviewed the results for 282 amniotic fluid samples that
      had been tested for CMV by a quantitative real-time PCR. We observed three cases
      in which no CMV genomes were detected in the AF but in which the children were
      nevertheless congenitally infected. Hence, we conclude that a negative result by
      PCR for CMV in AF cannot rule out the possibility of congenital infection. No
      false-positive PCR results were observed. A correlation between the CMV viral
      load in AF and the fetal and neonatal outcomes could not be demonstrated in our
      study. Instead, a correlation was found between the CMV viral load and the
      gestational age at the time of amniocentesis.

PMID- 19109475
TI  - Clostridium glycolicum isolated from a patient with otogenic brain abscesses.
AB  - We describe a case of brain abscesses with gas formation following otitis media,
      for which the patient treated himself by placing clay in his ear. Several
      microorganisms, including Clostridium glycolicum, were cultured from material
      obtained from the patient. This is the first report of an infection in an
      immunocompetent patient associated with this microorganism.

PMID- 19109476
TI  - Gordonia araii infection associated with an orthopedic device and review of the
      literature on medical device-associated Gordonia infections.
AB  - Gordonia infections in humans are rare and usually affect immunocompromised
      patients. We present the first case of Gordonia araii infection associated with a
      medical device in an immunocompetent patient. Sequencing was required for
      conclusive identification. We compared our case to the 16 Gordonia species
      associated medical device infections reported to date.

PMID- 19109477
TI  - Evolution of central nervous system multidrug-resistant Mycobacterium
      tuberculosis and late relapse of cryptic prosthetic hip joint tuberculosis:
      complications during treatment of disseminated isoniazid-resistant tuberculosis
      in an immunocompromised host.
AB  - We report a case of disseminated isoniazid-resistant tuberculosis in an
      immunocompromised patient with evolution of rifampin (rifampicin) resistance in
      the central nervous system. This was cured with intraventricular and oral
      treatment but was followed by a late relapse of the original infection in a
      prosthetic hip joint. We provide drug levels in cerebrospinal fluid and serum.

PMID- 19109478
TI  - Detection and toxin typing of Clostridium perfringens in formalin-fixed, paraffin
      embedded tissue samples by PCR.
AB  - Since current microbiology methods are not suitable to detect Clostridium
      perfringens in formalin-fixed, paraffin-embedded tissue samples, we developed a
      PCR assay to detect toxin-encoding genes and the 16S rRNA gene of C. perfringens.
      We successfully detected and genotyped C. perfringens in tissue sections from two
      autopsy cases.

PMID- 19109479
TI  - Value of serial quantification of fungal DNA by a real-time PCR-based technique
      for early diagnosis of invasive Aspergillosis in patients with febrile
      neutropenia.
AB  - A study was designed to assess the reliability of the serial detection of
      Aspergillus sp. DNA to diagnose invasive aspergillosis (IA) in patients with
      febrile neutropenia. Two blood and two serum samples were taken weekly from 83
      patients. A total of 2,244 samples were analyzed by real-time quantitative PCR.
      Twelve (14.4%) patients were diagnosed with IA. Taking two consecutive positive
      results as the diagnostic criterion, PCR detected 11 cases, with 4 false
      positives, giving sensitivity, specificity, positive, and negative predictive
      values of 91.6%, 94.4%, 73.3%, and 98.5%, respectively. On analyzing in
      conjunction with high-resolution chest tomography (HRCT) and galactomannan (GM)
      testing, the combination of serial PCR and GM detected 100% of aspergillosis
      cases, with a positive predictive value of 75.1%. This diagnostic strategy
      presented, according to CART analysis, a receiver-operator curve with an area
      under the curve of 0.97 (95% confidence interval, 0.895 to 1.032; P < 0.01), with
      a relative risk of IA 6.92 times higher than the control population and with
      predictive success of 95.2%. As regards early diagnosis, the serial detection of
      Aspergillus DNA took on average 21 days less than HRCT and 68 days less than GM.
      The serial detection of Aspergillus DNA using real-time quantitative PCR has
      great diagnostic applicability, which increases when combined with GM
      quantification.

PMID- 19109480
TI  - Oral abscess caused by Campylobacter rectus: case report and literature review.
AB  - Campylobacter rectus was isolated under routine anaerobic conditions (no
      additional hydrogen gas in the atmosphere) from an oral, nonperiodontal abscess
      from a patient with gastroesophageal adenocarcinoma. We report the first case of
      a palate abscess caused by C. rectus and review the literature and atmospheric
      requirements of this organism.

PMID- 19109481
TI  - Neisseria gonorrhoeae endocarditis confirmed by nucleic acid amplification assays
      performed on aortic valve tissue.
AB  - The Aptima Combo 2 assay is proposed as a rapid method of diagnosing Neisseria
      gonorrhoeae endocarditis or other suspected disseminated gonococcal disease.

PMID- 19109482
TI  - Population snapshot of Streptococcus pneumoniae serotype 19A isolates before and
      after introduction of seven-valent pneumococcal Vaccination for French children.
AB  - Serotype 19A Streptococcus pneumoniae strains are now more frequent in French
      children than before the introduction of a seven-valent conjugate vaccine (PCV7).
      By applying multilocus sequence typing to 144 serotype 19A isolates collected
      before and after beginning PCV7 vaccination, we detected clonal expansion of the
      preexisting penicillin-intermediate sequence type 276.

PMID- 19109483
TI  - Practical considerations for high-throughput influenza A virus surveillance
      studies of wild birds by use of molecular diagnostic tests.
AB  - Influenza A virus surveillance studies of wild bird populations are essential to
      improving our understanding of the role of wild birds in the ecology of low
      pathogenic avian influenza viruses and their potential contribution to the spread
      of H5N1 highly pathogenic avian influenza viruses. Whereas the primary results of
      such surveillance programs have been communicated extensively, practical
      considerations and technical implementation options generally receive little
      attention. In the present study, the data obtained from 39,490 samples were used
      to compare the impacts of variables such as the sampling procedure, storage and
      transport conditions, and the choice of molecular and classical diagnostic tests
      on the outcome of the results. Molecular diagnostic tests allowed estimation of
      the virus load in samples, which has implications for the ability to isolate
      virus. Virus isolation in embryonated eggs was more sensitive than virus
      isolation in cell cultures. Storage and transport conditions had less of an
      impact on diagnostics by the use of molecular tests than by the use of classical
      approaches. These findings indicate that molecular diagnostic tests are more
      sensitive and more reliable than classical tests. In addition, molecular
      diagnostic tests facilitated analyses in real time and allowed the discrimination
      of H5 influenza viruses with low and high pathogenicities without the need for
      virus isolation. Critical assessment of the methods used in large surveillance
      studies like this will facilitate comparison of the results between studies.
      Moreover, the lessons learned from current large-scale influenza A virus
      surveillance activities could be valuable for other pathogen surveillance
      programs in the future.

PMID- 19109484
TI  - Sex differences in micro-opioid receptor expression in the rat midbrain
      periaqueductal gray are essential for eliciting sex differences in morphine
      analgesia.
AB  - Opioid-based narcotics are the most widely prescribed therapeutic agent for the
      alleviation of persistent pain; however, it is becoming increasingly clear that
      morphine is significantly less potent in women compared with men. Morphine
      primarily binds to mu-opioid receptors (MORs), and the periaqueductal gray (PAG)
      contains a dense population of MOR-expressing neurons. Via its descending
      projections to the rostral ventromedial medulla and the dorsal horn of the spinal
      cord, the PAG is considered an essential neural substrate for opioid-based
      analgesia. We hypothesized that MOR expression in the PAG was sexually dimorphic,
      and that these sex differences contribute to the observed sex differences in
      morphine potency. Using immunohistochemistry, we report that males had a
      significantly higher expression of MOR in the ventrolateral PAG compared with
      cycling females, whereas the lowest level of expression was observed in proestrus
      females. CFA-induced inflammatory pain produced thermal hyperalgesia in both
      males and females that was significantly reversed in males with a microinjection
      of morphine into the ventrolateral PAG; this effect was significantly greater
      than that observed in proestrus and estrus females. Selective lesions of MOR
      expressing neurons in the ventrolateral PAG resulted in a significant reduction
      in the effects of systemic morphine in males only, and this reduction was
      positively correlated with the level of MOR expression in the ventrolateral PAG.
      Together, these results provide a mechanism for sex differences in morphine
      potency.

PMID- 19109485
TI  - D2 dopamine receptor activation facilitates endocannabinoid-mediated long-term
      synaptic depression of GABAergic synaptic transmission in midbrain dopamine
      neurons via cAMP-protein kinase A signaling.
AB  - Endocannabinoid (eCB) signaling mediates short-term and long-term synaptic
      depression (LTD) in many brain areas. In the ventral tegmental area (VTA) and
      striatum, D(2) dopamine receptors cooperate with group I metabotropic glutamate
      receptors (mGluRs) to induce eCB-mediated LTD of glutamatergic excitatory and
      GABAergic inhibitory (I-LTD) synaptic transmission. Because D(2) receptors and
      group I mGluR agonists are capable of inducing the release of eCBs, the
      predominant hypothesis is that the cooperation between these receptors to induce
      eCB-mediated synaptic depression results from the combined activation of type I
      cannabinoid (CB(1)) receptors by the eCBs. By determining the downstream
      effectors for D(2) receptor and group I mGluR activation in VTA dopamine neurons,
      we show that group I mGluR activation contributes to I-LTD induction by enhancing
      eCB release and CB(1) receptor activation. However, D(2) receptor activation does
      not enhance CB(1) receptor activation, but facilitates I-LTD induction via direct
      inhibition of cAMP-dependent protein kinase A (PKA) signaling. We further
      demonstrate that cAMP/PKA signaling pathway is the downstream effector for CB(1)
      receptors and is required for eCB-mediated I-LTD induction. Our results suggest
      that D(2) receptors and CB(1) receptors target the same downstream effector
      cAMP/PKA signaling pathway to induce I-LTD and D(2) receptor activation
      facilitates eCB-mediated I-LTD in dopamine neurons not by enhancing CB(1)
      receptor activation, but by enhancing its downstream effects.

PMID- 19109486
TI  - Postsynaptic action potentials are required for nitric-oxide-dependent long-term
      potentiation in CA1 neurons of adult GluR1 knock-out and wild-type mice.
AB  - Neocortical long-term potentiation (LTP) consists of both presynaptic and
      postsynaptic components that rely on nitric oxide (NO) and the GluR1 subunit of
      the AMPA receptor, respectively. In this study, we found that hippocampal LTP,
      induced by theta-burst stimulation in mature (>8-week-old) GluR1 knock-out mice
      was almost entirely NO dependent and involved both the alpha splice variant of NO
      synthase-1 and the NO synthase-3 isoforms of NO synthase. Theta-burst induced LTP
      was also partly NO-dependent in wild-type mice and made up approximately 50% of
      the potentiation 2 h after tetanus. Theta-burst stimulation reliably produced
      postsynaptic spikes, including a high probability of complex spikes. Inhibition
      of postsynaptic somatic spikes with intracellular QX314 or local TTX application
      prevented LTP in the GluR1 knock-out mice and also blocked the NO component of
      LTP in wild types. We conclude that theta-burst stimulation is particularly well
      suited to producing the postsynaptic somatic spikes required for NO-dependent
      LTP.

PMID- 19109487
TI  - Bidirectional Hebbian plasticity at hippocampal mossy fiber synapses on CA3
      interneurons.
AB  - Hippocampal area CA3 is critically involved in the formation of nonoverlapping
      neuronal subpopulations ("pattern separation") to store memory representations as
      distinct events. Efficient pattern separation relies on the strong and sparse
      excitatory input from the mossy fibers (MFs) to pyramidal cells and feedforward
      inhibitory interneurons. However, MF synapses on CA3 pyramidal cells undergo long
      term potentiation (LTP), which, if unopposed, will degrade pattern separation
      because MF activation will now recruit additional CA3 pyramidal cells. Here, we
      demonstrate MF LTP in stratum lacunosum-moleculare (L-M) interneurons induced by
      the same stimulation protocol that induces MF LTP in pyramidal cells. This LTP
      was NMDA receptor (NMDAR) independent and occurred at MF Ca(2+)-impermeable AMPA
      receptor synapses. LTP was prevented by with voltage clamping the postsynaptic
      cell soma during high-frequency stimulation (HFS), intracellular injections of
      the Ca(2+) chelator BAPTA (20 mm), or bath applications of the L-type Ca(2+)
      channel blocker nimodipine (10 microm). We propose that MF LTP in L-M
      interneurons preserves the sparsity of pyramidal cell activation, thus allowing
      CA3 to maintain its role in pattern separation. In the presence of the
      mGluR1alpha antagonist LY367385 [(S)-(+)-a-amino-4-carboxy-2-methylbenzeneacetic
      acid] (100 microm), the same HFS that induces MF LTP in naive slices triggered
      NMDAR-independent MF LTD. This LTD, like LTP, required activation of the L-type
      Ca(2+) channel and also was induced after blockade of IP(3) receptors with
      heparin (4 mg/ml) or the selective depletion of receptor-gated Ca(2+) stores with
      ryanodine (10 or 100 microm). We conclude that L-M interneurons are endowed with
      Ca(2+) signaling cascades suitable for controlling the polarity of MF long-term
      plasticity induced by joint presynaptic and postsynaptic activities.

PMID- 19109488
TI  - Control of motoneuron survival by angiogenin.
AB  - Mutations in the hypoxia-inducible factor angiogenin (ANG) have been identified
      in Amyotrophic Lateral Sclerosis (ALS) patients, but the potential role of ANG in
      ALS pathogenesis was undetermined. Here we show that angiogenin promotes
      motoneuron survival both in vitro and in vivo. Angiogenin protected cultured
      motoneurons against excitotoxic injury in a PI-3-kinase/Akt kinase-dependent
      manner, whereas knock-down of angiogenin potentiated excitotoxic motoneuron
      death. Expression of wild-type ANG protected against endoplasmic reticulum (ER)
      stress-induced and trophic-factor-withdrawal-induced cell death in vitro, whereas
      the ALS-associated ANG mutant K40I exerted no protective activity and failed to
      activate Akt-1. In SOD1(G93A) mice angiogenin delivery increased lifespan and
      motoneuron survival, restored the disease-associated decrease in Akt-1 survival
      signaling, and reversed a pathophysiological increase in ICAM-1 expression. Our
      data demonstrate that angiogenin is a key factor in the control of motoneuron
      survival.

PMID- 19109489
TI  - Nociceptors are interleukin-1beta sensors.
AB  - A cardinal feature of inflammation is heightened pain sensitivity at the site of
      the inflamed tissue. This results from the local release by immune and injured
      cells of nociceptor sensitizers, including prostaglandin E(2), bradykinin, and
      nerve growth factor, that reduce the threshold and increase the excitability of
      the peripheral terminals of nociceptors so that they now respond to innocuous
      stimuli: the phenomenon of peripheral sensitization. We show here that the
      proinflammatory cytokine interleukin-1beta (IL-1beta), in addition to producing
      inflammation and inducing synthesis of several nociceptor sensitizers, also
      rapidly and directly activates nociceptors to generate action potentials and
      induce pain hypersensitivity. IL-1beta acts in a p38 mitogen-activated protein
      kinase (p38 MAP kinase)-dependent manner, to increase the excitability of
      nociceptors by relieving resting slow inactivation of tetrodotoxin-resistant
      voltage-gated sodium channels and also enhances persistent TTX-resistant current
      near threshold. By acting as an IL-1beta sensor, nociceptors can directly signal
      the presence of ongoing tissue inflammation.

PMID- 19109490
TI  - Id2 is required for specification of dopaminergic neurons during adult olfactory
      neurogenesis.
AB  - Understanding the biology of adult neural stem cells has important implications
      for nervous system development and may contribute to our understanding of
      neurodegenerative disorders and their treatment. We have characterized the
      process of olfactory neurogenesis in adult mice lacking inhibitor of DNA binding
      2(-/-) (Id2(-/-)). We found a diminished olfactory bulb containing reduced
      numbers of granular and periglomerular neurons with a distinct paucity of
      dopaminergic periglomerular neurons. While no deficiency of the stem cell
      compartment was detectable, migrating neuroblasts in Id2(-/-) mutant mice
      prematurely undergo astroglial differentiation within a disorganized rostral
      migratory stream. Further, when evaluated in vitro loss of Id2 results in
      decreased proliferation of neural progenitors and decreased expression of the
      Hes1 and Ascl1 (Mash1) transcription factors, known mediators of neuronal
      differentiation. These data support a novel role for sustained Id2 expression in
      migrating neural progenitors mediating olfactory dopaminergic neuronal
      differentiation in adult animals.

PMID- 19109491
TI  - Activation of the neuronal extracellular signal-regulated kinase 2 in the spinal
      cord dorsal horn is required for complete Freund's adjuvant-induced pain
      hypersensitivity.
AB  - Extracellular signal-regulated kinase 1 (ERK1) and ERK2 signaling in the spinal
      cord dorsal horn (SCDH) has been implicated in injury-induced pain
      hypersensitivity. Available ERK pathway inhibitors cannot distinguish between
      ERK1 and ERK2, nor can they differentially target the expression of neuronal or
      glial ERK1/2. We selectively inhibited the expression of ERK2 in neurons of the
      adult mouse SCDH by use of an ERK2 small interfering RNA (siRNA) delivered by a
      neurotropic adenoassociated viral vector. In situ hybridization revealed a siRNA
      vector-induced decrease in ERK2 mRNA in the ipsilateral SCDH.
      Immunohistochemistry showed a decreased neuronal phospho-ERK1/2 (pERK1/2), and
      Western blot analysis revealed that both ERK2 expression and phosphorylation were
      reduced by the siRNA vector. In contrast, basal ERK1 expression was not affected,
      although pERK1 was slightly increased. The siRNA vector-induced knockdown of ERK2
      expression in the SCDH did not alter the baseline mechanical or thermal paw
      withdrawal thresholds. Hindpaw intraplantar injection of complete Freund's
      adjuvant (CFA) produced peripheral inflammation, mechanical allodynia, and
      thermal hyperalgesia in vector control animals that persisted for at least 96 h.
      It also caused an increase in SCDH ERK1 and ERK2 levels at 96 h and pERK1 and
      pERK2 levels at 1 and 96 h. The ERK2 siRNA vector prevented changes in ERK1,
      ERK2, and pERK2. In addition, the siRNA vector protected the animals from
      developing mechanical allodynia and thermal hyperalgesia throughout the 96 h
      after CFA. These findings indicate that ERK2 in the SCDH neurons is critical for
      the development of inflammatory pain hypersensitivity.

PMID- 19109492
TI  - Lmx1b-controlled isthmic organizer is essential for development of midbrain
      dopaminergic neurons.
AB  - The LIM homeodomain transcription factor Lmx1b has been suggested to be required
      for the differentiation of midbrain dopaminergic (mDA) neurons. However, whether
      the loss of mDA neurons in Lmx1b(-/-) mice is due to its intrinsic role in the
      mDA lineage or to a consequence of the malformations caused by the earlier
      mid/hindbrain patterning defects remains to be clarified. We report here that
      Lmx1b expression in mDA neurons is dispensable for their differentiation and
      maintenance, and the loss of mDA neurons in Lmx1b(-/-) mice is due to the
      disruption of inductive activity of the isthmic organizer (IsO) in the absence of
      Lmx1b at the mid/hindbrain boundary (MHB). We found that mDA neurons revealed by
      tyrosine hydroxylase (TH), Pitx3, Nurr1, and dopamine transporter were
      indistinguishable from wild-type controls during embryonic development as well as
      in adulthood in TH-Cre;Lmx1b(flox/-) and Dat(Cre/+);Lmx1b(flox/-) mice, in which
      Lmx1b was selectively deleted in differentiating mDA neurons. In addition, mDA
      neurons were recovered in Lmx1b(-/-) mice, when IsO activity was restored by Wnt1
      Lmx1b transgene at MHB. The restored IsO activity was evidenced by apparently
      normal tectum and cerebellum and recurrence of expression of Fgf8 and Wnt1 at MHB
      in Wnt1(Lmx1b);Lmx1b(-/-). Furthermore, when Lmx1b was deleted in the whole brain
      after the formation of IsO by Nestin-Cre, mDA neurons were normal, whereas
      serotonergic neurons displayed defective development phenocopying what observed
      in Lmx1b(-/-) mice. Thus, our results indicate that the inductive activity of IsO
      is essential, but Lmx1b expression in mDA neurons is dispensable for their
      differentiation and maintenance.

PMID- 19109494
TI  - Four excitatory postsynaptic ionotropic receptors coactivated at the motoneuron
      Renshaw cell synapse.
AB  - Renshaw cells (RCs) are spinal interneurons excited by collaterals of the axons
      of motoneurons (MNs). They respond to a single motoneuronal volley by a
      surprisingly long (tens of milliseconds) train of action potentials. We have
      analyzed this synaptic response in spinal cord slices of neonatal mice in light
      of recent observations suggesting that the MN axons release both acetylcholine
      and glutamate. We found that the RC synaptic current involves four components of
      similar amplitudes mediated by two nicotinic receptors (nAChRs, tentatively
      identified as alpha(7) homomers and alpha(4)beta(2) heteromers) and two glutamate
      receptors (AMPARs and NMDARs). The decay time constants of the four components
      cover a wide range: from 3.6 +/- 2.2 ms (alpha(7) nAChRs) to 54.6 +/- 19.5 ms
      (NMDARs, at -45 mV). The RC discharge can be separated into an initial doublet of
      high-frequency action potentials followed by later spikes with a variable latency
      and longer interspike intervals. The initial doublet involves the four ionotropic
      receptors as well as endogenous voltage-dependent conductances. The late
      discharge depends on NMDARs, but these receptors must be primed by the initial
      depolarization. The activation of the NMDARs is prolonged by the fact that their
      slow deactivation is further slowed by depolarization. The formation of the
      initial doublet is favored by hyperpolarization, whereas the late discharge is
      favored by depolarization. This suggests that in physiological conditions the
      pattern of discharge of the RC in response to a MN input may alternate between a
      phasic and a tonic response.

PMID- 19109493
TI  - The yellow fluorescent protein (YFP-H) mouse reveals neuroprotection as a novel
      mechanism underlying chondroitinase ABC-mediated repair after spinal cord injury.
AB  - Chondroitinase ABC (ChABC) represents a promising therapeutic strategy for the
      treatment of spinal cord injury due to its potent effects on restoring function
      to spinal-injured adult mammals. However, there is limited mechanistic insight as
      to the underlying effects of ChABC treatment, where the effects are mediated, and
      which signaling pathways are involved in ChABC-mediated repair. Here we use a
      transgenic (YFP-H) mouse to demonstrate that cortical layer V projection neurons
      undergo severe atrophy 4 weeks after thoracic dorsal column injury and that ChABC
      is neuroprotective for these neurons after ICV infusion. ChABC also prevented
      cell atrophy after localized delivery to the spinal cord, suggesting a possible
      retrograde neuroprotective effect mediated at the injury site. Furthermore,
      neuroprotection of corticospinal cell somata coincided with increased axonal
      sprouting in the spinal cord. In addition, Western blot analysis of a number of
      kinases important in survival and growth signaling revealed a significant
      increase in phosphorylated ERK1 at the spinal injury site after in vivo ChABC
      treatment, indicating that activated ERK may play a role in downstream repair
      processes after ChABC treatment. Total forms of PKC and AKT were also elevated,
      indicating that modification of the glial scar by ChABC promotes long-lasting
      signaling changes at the lesion site. Thus, using the YFP-H mouse as a novel tool
      to study degenerative changes and repair after spinal cord injury we demonstrate,
      for the first time, that ChABC treatment regulates multiple signaling cascades at
      the injury site and exerts protective effects on axotomized corticospinal
      projection neurons.

PMID- 19109495
TI  - Explaining function with anatomy: language lateralization and corpus callosum
      size.
AB  - The anatomy of the corpus callosum (CC) has been advocated as a potential marker
      for functional lateralization because its size is supposedly proportional to the
      number of fibers connecting the hemispheres. Previous morphometric studies of
      this relationship have compared CC size in groups of subjects who are more or
      less likely to show differences in their lateralization (e.g., left vs right
      handers). The findings, however, have been inconsistent, and to our knowledge, no
      previous study has directly compared CC size with lateralization assessed by
      functional imaging data. We therefore combined anatomical measurements of CC size
      with left versus right hemisphere language activation in 74 normal subjects.
      After controlling for perceptual and motor output effects, as well as for global
      white-matter volume, handedness, gender and age, we found that subjects who had a
      larger CC showed more left lateralization for language in posterior temporal and
      inferior frontal regions. Examination of these effects revealed that, as CC size
      increased, stronger lateralization resulted from more left hemisphere activation
      in both regions as well as reduced right hemisphere activation in the posterior
      temporal region. Our observations provide the first clear evidence in normal
      subjects that the midsagittal surface area of the CC contributes to the degree to
      which language is functionally lateralized. We discuss the complex
      interhemispheric processes that might underlie this effect.

PMID- 19109496
TI  - Seeing versus believing: conflicting immediate and predicted feedback lead to
      suboptimal motor performance.
AB  - Reaching hand movements tend to follow straight paths. Previous work has
      suggested that when visual feedback is perturbed such that straight hand motions
      are seen as curved motions, the motor system adapts to restore straight visual
      motion. We show that under a nonlinear visuomotor transformation, one that maps
      straight hand motions to high-curvature motions of a visual cursor, reaching
      movements do not converge with practice toward a straight path of either the hand
      or the cursor. Instead, hand trajectories converged to a repeatable and
      characteristic curved shape. We propose a new computational model in which the
      adapted trajectories are obtained by minimizing a cost function composed of two
      terms. The first term enforces hand-movement smoothness. The second term
      penalizes average visual aiming error, which is the instantaneous discrepancy
      between the direction of the hand movement and the direction of the vector that
      points from the cursor to the target. Our results are consistent with the model's
      predictions and demonstrate a persistent effect of the predicted feedback of
      direction errors despite the possibility of producing smoother hand motions by
      ignoring it.

PMID- 19109497
TI  - Increasing human brain excitability by transcranial high-frequency random noise
      stimulation.
AB  - For >20 years, noninvasive transcranial stimulation techniques like repetitive
      transcranial magnetic stimulation (rTMS) and direct current stimulation (tDCS)
      have been used to induce neuroplastic-like effects in the human cortex, leading
      to the activity-dependent modification of synaptic transmission. Here, we
      introduce a novel method of electrical stimulation: transcranial random noise
      stimulation (tRNS), whereby a random electrical oscillation spectrum is applied
      over the motor cortex. tRNS induces consistent excitability increases lasting 60
      min after stimulation. These effects have been observed in 80 subjects through
      both physiological measures and behavioral tasks. Higher frequencies (100-640 Hz)
      appear to be responsible for generating this excitability increase, an effect
      that may be attributed to the repeated opening of Na(+) channels. In terms of
      efficacy tRNS appears to possess at least the same therapeutic potential as
      rTMS/tDCS in diseases such as depression, while furthermore avoiding the
      constraint of current flow direction sensitivity characteristic of tDCS.

PMID- 19109498
TI  - Rapid microglial response around amyloid pathology after systemic anti-Abeta
      antibody administration in PDAPP mice.
AB  - Aggregation of amyloid-beta (Abeta) peptide in the brain in the form of neuritic
      plaques and cerebral amyloid angiopathy (CAA) is a key feature of Alzheimer's
      disease (AD). Microglial cells surround aggregated Abeta and are believed to play
      a role in AD pathogenesis. A therapy for AD that has entered clinical trials is
      the administration of anti-Abeta antibodies. One mechanism by which certain anti
      Abeta antibodies have been proposed to exert their effects is via antibody
      mediated microglial activation. Whether, when, or to what extent microglial
      activation occurs after systemic administration of anti-Abeta antibodies has not
      been fully assessed. We administered an anti-Abeta antibody (m3D6) that binds
      aggregated Abeta to PDAPP mice, an AD mouse model that was bred to contain
      fluorescent microglia. Three days after systemic administration of m3D6, there
      was a marked increase in both the number of microglial cells and processes per
      cell visualized in vivo by multiphoton microscopy. These changes required the Fc
      domain of m3D6 and were not observed with an antibody specific to soluble Abeta.
      These findings demonstrate that some effects of antibodies that recognize
      aggregated Abeta are rapid, involve microglia, and provide insight into the
      mechanism of action of a specific passive immunotherapy for AD.

PMID- 19109499
TI  - Specificity of reflex adaptation for task-relevant variability.
AB  - The motor system responds to perturbations with reflexes, such as the vestibulo
      ocular reflex or stretch reflex, whose gains adapt in response to novel and fixed
      changes in the environment, such as magnifying spectacles or standing on a
      tilting platform. Here we demonstrate a reflex response to shifts in the hand's
      visual location during reaching, which occurs before the onset of voluntary
      reaction time, and investigate how its magnitude depends on statistical
      properties of the environment. We examine the change in reflex response to two
      different distributions of visuomotor discrepancies, both of which have zero mean
      and equal variance across trials. Critically one distribution is task relevant
      and the other task irrelevant. The task-relevant discrepancies are maintained to
      the end of the movement, whereas the task-irrelevant discrepancies are transient
      such that no discrepancy exists at the end of the movement. The reflex magnitude
      was assessed using identical probe trials under both distributions. We find
      opposite directions of adaptation of the reflex response under these two
      distributions, with increased reflex magnitudes for task-relevant variability and
      decreased reflex magnitudes for task-irrelevant variability. This demonstrates
      modulation of reflex magnitudes in the absence of a fixed change in the
      environment, and shows that reflexes are sensitive to the statistics of tasks
      with modulation depending on whether the variability is task relevant or task
      irrelevant.

PMID- 19109500
TI  - Origin of the voltage dependence of G-protein regulation of P/Q-type Ca2+
      channels.
AB  - G-protein (Gbetagamma)-mediated voltage-dependent inhibition of N- and P/Q-type
      Ca(2+) channels contributes to presynaptic inhibition and short-term synaptic
      plasticity. The voltage dependence derives from the dissociation of Gbetagamma
      from the inhibited channels, but the underlying molecular and biophysical
      mechanisms remain largely unclear. In this study we investigated the role in this
      process of Ca(2+) channel beta subunit (Ca(v)beta) and a rigid alpha-helical
      structure between the alpha-interacting domain (AID), the primary Ca(v)beta
      docking site on the channel alpha(1) subunit, and the pore-lining IS6 segment.
      Gbetagamma inhibition of P/Q-type channels was reconstituted in giant inside-out
      membrane patches from Xenopus oocytes. Large populations of channels devoid of
      Ca(v)beta were produced by washing out a mutant Ca(v)beta with a reduced affinity
      for the AID. These beta-less channels were still inhibited by Gbetagamma, but
      without any voltage dependence, indicating that Ca(v)beta is indispensable for
      voltage-dependent Gbetagamma inhibition. A truncated Ca(v)beta containing only
      the AID-binding guanylate kinase (GK) domain could fully confer voltage
      dependence to Gbetagamma inhibition. Gbetagamma did not alter inactivation
      properties, and channels recovered from Gbetagamma inhibition exhibited the same
      activation property as un-inhibited channels, indicating that Gbetagamma does not
      dislodge Ca(v)beta from the inhibited channel. Furthermore, voltage-dependent
      Gbetagamma inhibition was abolished when the rigid alpha-helix between the AID
      and IS6 was disrupted by insertion of multiple glycines, which also eliminated
      Ca(v)beta regulation of channel gating, revealing a pivotal role of this rigid
      alpha-helix in both processes. These results suggest that depolarization
      triggered movement of IS6, coupled to the subsequent conformational change of the
      Gbetagamma-binding pocket through a rigid alpha-helix induced partly by the
      Ca(v)beta GK domain, causes the dissociation of Gbetagamma and is fundamental to
      voltage-dependent Gbetagamma inhibition.

PMID- 19109501
TI  - Recovery from chronic demyelination by thyroid hormone therapy: myelinogenesis
      induction and assessment by diffusion tensor magnetic resonance imaging.
AB  - The failure of the remyelination processes in multiple sclerosis contributes to
      the formation of chronic demyelinated plaques that lead to severe neurological
      deficits. Long-term cuprizone treatment of C57BL/6 mice resulted in pronounced
      white matter pathology characterized by oligodendrocyte depletion, irreversible
      demyelination and persistent functional deficits after cuprizone withdrawal. The
      use of a combination of in vivo diffusion tensor magnetic resonance imaging (DT
      MRI) and histological analyses allowed for an accurate longitudinal assessment of
      demyelination. Injection of triiodothyronine (T(3)) hormone over a 3 week
      interval after cuprizone withdrawal progressively restored the normal DT-MRI
      phenotype accompanied by an improvement of clinical signs and remyelination. The
      effects of T(3) were not restricted to the later stages of remyelination but
      increased the expression of sonic hedgehog and the numbers of Olig2(+) and PSA
      NCAM(+) precursors and proliferative cells. Our findings establish a role for
      T(3) as an inducer of oligodendrocyte progenitor cells in adult mouse brain
      following chronic demyelination.

PMID- 19109502
TI  - Signaling through cGMP-dependent protein kinase I in the amygdala is critical for
      auditory-cued fear memory and long-term potentiation.
AB  - Long-term potentiation (LTP) of inputs relaying sensory information from cortical
      and thalamic neurons to principal neurons in the lateral amygdala (LA) is thought
      to serve as a cellular mechanism for associative fear learning. Nitric oxide
      (NO), a messenger molecule widely implicated in synaptic plasticity and behavior,
      has been shown to enhance LTP in the LA as well as consolidation of associative
      fear memory. Additional evidence suggests that NO-induced enhancement of LTP and
      amygdala-dependent learning requires signaling through soluble guanylyl cyclase
      (sGC) and cGMP-dependent protein kinase (cGK). Mammals possess two genes for cGK:
      the prkg1 gene gives rise to the cGK type I isoforms, cGKIalpha and cGKIbeta, and
      the prkg2 gene encodes the cGK type II. Reportedly, both cGKI and cGKII are
      expressed in the amygdala, and cGKII is involved in controlling anxiety-like
      behavior. Because selective pharmacological tools for individual cGK isoforms are
      lacking, we used different knock-out mouse models to examine the function of cGKI
      and cGKII for LTP in the LA and pavlovian fear conditioning. We found robust
      expression of the cGKI specifically in the LA with cGKIbeta as the prevailing
      isoform. We further show a marked reduction of LTP at both thalamic and cortical
      inputs to the LA and a selective impairment of auditory-cued fear memory in cGKI
      deficient mutants. In contrast, cGKII null mutants lack these phenotypes. Our
      data suggest a function of cGKI, likely the beta isoform, in the LA, supporting
      synaptic plasticity and consolidation of fear memory.

PMID- 19109504
TI  - Prolonged perceptual learning of positional acuity in adult amblyopia: perceptual
      template retuning dynamics.
AB  - Amblyopia is a developmental abnormality that results in physiological
      alterations in the visual cortex and impairs form vision. It is often
      successfully treated by patching the sound eye in infants and young children, but
      is generally considered to be untreatable in adults. However, a number of recent
      studies suggest that repetitive practice of a visual task using the amblyopic eye
      results in improved performance in both children and adults with amblyopia. These
      perceptual learning studies have used relatively brief periods of practice;
      however, clinical studies have shown that the time-constant for successful
      patching is long. The time-constant for perceptual learning in amblyopia is still
      unknown. Here we show that the time-constant for perceptual learning depends on
      the degree of amblyopia. Severe amblyopia requires >50 h (approximately equal to
      35,000 trials) to reach plateau, yielding as much as a five-fold improvement in
      performance at a rate of approximately equal to 1.5%/h. There is significant
      transfer of learning from the amblyopic to the dominant eye, suggesting that the
      learning reflects alterations in higher decision stages of processing. Using a
      reverse correlation technique, we document, for the first time, a dynamic
      retuning of the amblyopic perceptual decision template and a substantial
      reduction in internal spatial distortion. These results show that the mature
      amblyopic brain is surprisingly malleable, and point to more intensive treatment
      methods for amblyopia.

PMID- 19109503
TI  - Multiple molecular interactions determine the clustering of Caspr2 and Kv1
      channels in myelinated axons.
AB  - Clustering of Kv1 channels at the juxtaparanodal region (JXP) in myelinated axons
      depends on their association with the Caspr2/TAG-1 adhesion complex. The
      interaction between these channels and Caspr2 was suggested to depend on PDZ (PSD
      95/Discs large/zona occludens-1) scaffolding proteins. Here, we show that at a
      subset of the JXP, PSD-93 colocalizes with Caspr2, K(+) channels and its related
      protein postsynaptic density protein-95 (PSD-95). The localization of PSD-93 and
      PSD-95 depends on the presence of Caspr2, as both scaffolding proteins failed to
      accumulate at the JXP in mice lacking either Caspr2 or TAG-1. In contrast, Caspr2
      and K(+) channels still colocalized and associated in PSD-93, PSD-95 or double
      PSD-93/PSD-95 null mice. To directly evaluate the role of PDZ domain proteins in
      the function of Caspr2, we examined the ability of transgenic Caspr2 molecules
      lacking either their cytoplasmic domain (Caspr2dCT), or their PDZ-binding
      sequence (Caspr2dPDZ), to restore Kv1 channel clustering in Caspr2 null mice. We
      found that while Kv1 channels were distributed throughout internodes in nerves
      expressing Caspr2dCT, they were clustered at the JXP in axons expressing a full
      length Caspr2 (Caspr2FL) or the Caspr2dPDZ transgene. Further proteomic analysis
      revealed that Caspr2 interacts with a distinct set of scaffolding proteins
      through its PDZ- and protein 4.1-binding sequences. These results demonstrate
      that while the molecular assembly of the JXP requires the cytoplasmic domain of
      Caspr2, its carboxy-terminal PDZ-binding motif is dispensable for Kv1 channel
      clustering. This mechanism is clearly distinct from the one operating at the axon
      initial segment, which requires PSD-93 for Kv1 channel clustering.

PMID- 19109505
TI  - Distinct roles for onset and sustained activity in the neuronal code for temporal
      periodicity and acoustic envelope shape.
AB  - Auditory neurons are selective for temporal sound information that is important
      for rhythm, pitch, and timbre perception. Traditional models assume that
      periodicity information is represented either by the discharge rate of tuned
      modulation filters or synchrony in the discharge pattern. Compelling evidence for
      an invariant rate or synchrony code, however, is lacking and neither of these
      models account for how the sound envelope shape is encoded. We examined the
      neuronal representation for envelope shape and periodicity in the cat central
      nucleus of the inferior colliculus (CNIC) with modulated broadband noise that
      lacks spectral cues and produces a periodicity pitch percept solely based on
      timing information. The modulation transfer functions of CNIC neurons differed
      dramatically across stimulus conditions with identical periodicity but different
      envelope shapes implying that shape contributed significantly to the neuronal
      response. We therefore devised a shuffled correlation procedure to quantify how
      periodicity and envelope shape contribute to the temporal discharge pattern.
      Sustained responses faithfully encode envelope shape at low modulation rates but
      deteriorate and fail to account for timing and envelope information at high
      rates. Surprisingly, onset responses accurately entrained to the stimulus and
      provided a means of encoding repetition information at high rates. Finally, we
      demonstrate that envelope shape information is accurately reflected in the
      population discharge pattern such that shape is readily discriminated for
      repetition frequencies up to approximately 100 Hz. These results argue against
      conventional rate- or synchrony-based codes and provide two complementary
      temporal mechanisms by which CNIC neurons can encode envelope shape and
      repetition information in natural sounds.

PMID- 19109506
TI  - Parkinsonian beta oscillations in the external globus pallidus and their
      relationship with subthalamic nucleus activity.
AB  - Inappropriately synchronized beta (beta) oscillations (15-30 Hz) in the
      subthalamic nucleus (STN) accompany movement difficulties in idiopathic
      Parkinson's disease (PD). The cellular and network substrates underlying these
      exaggerated beta oscillations are unknown but activity in the external globus
      pallidus (GP), which forms a candidate pacemaker network with STN, might be of
      particular importance. Using a clinically relevant rat model of PD, we
      demonstrate that oscillatory activity in GP neuronal networks becomes excessively
      and selectively synchronized at beta frequencies in a spatially widespread and
      brain state-dependent manner after lesion of dopamine neurons. Although
      synchronization of GP unit activity increased by almost 100-fold during beta
      oscillations, the mean firing rate of GP neurons decreased compared with
      controls. Importantly, in parkinsonian animals, two main types of GP neuron were
      identified according to their distinct and inversely related firing rates and
      patterns. Moreover, neurons of the same type tended to fire together, with small
      phase differences, whereas different types of neuron tended not to do so. This
      functional dichotomy in temporal coupling persisted across extreme brain states,
      suggesting that maladaptive interactions are dominated by hardwiring. Finally,
      the precisely timed discharges of GP and STN neurons indicated that rhythmic
      sequences of recurrent excitation and inhibition in the STN-GP network, and
      lateral inhibition between GP neurons, could actively support abnormal beta
      oscillations. We propose that GP neurons, by virtue of their spatiotemporal
      synchronization, widespread axon collaterals and feed-back/feed-forward
      mechanisms, are well placed to orchestrate and propagate exaggerated beta
      oscillations throughout the entire basal ganglia in PD.

PMID- 19109507
TI  - Hypoxia-inducible factor-1alpha protects cultured cortical neurons from
      lipopolysaccharide-induced cell death via regulation of NR1 expression.
AB  - Inflammation is involved in some neurodegenerative disorders. NMDA glutamate
      receptors play an important role in neuronal development. Here, we show that NR1
      expression in the cerebral cortex and primary neurons of rats was upregulated
      after lipopolysaccharide (LPS) treatment. This increase in NR1 expression was
      considered to be strongly associated with hypoxia-inducible factor-1alpha (HIF
      1alpha) activation because the treatment of primary neurons with either
      echinomycin or small interfering RNA (siRNA) targeting HIF-1alpha could block NR1
      expression. HIF-1alpha could be induced by an increase in the translational
      efficiency of the cells. After this, it was transported into the nucleus where it
      bound to the NR1 promoter and regulated the induction of NR1 transcriptional
      activity by LPS. LPS injection into the prefrontal cortex caused neuronal death,
      and this condition was aggravated by intracerebroventricular injection of
      echinomycin. Furthermore, knockdown of HIF-1alpha and NR1 by the appropriate
      siRNAs reduced the neurite outgrowth and viability of the primary neurons. These
      results suggest that NR1 expression is regulated by HIF-1alpha and plays a
      protective role in neurons during LPS challenge.

PMID- 19109508
TI  - Network dynamics underlying the formation of sparse, informative representations
      in the hippocampus.
AB  - During development, activity-dependent processes increase the specificity of
      neural responses to stimuli, but the role that this type of process plays in
      adult plasticity is unclear. We examined the dynamics of hippocampal activity as
      animals learned about new environments to understand how neural selectivity
      changes with experience. Hippocampal principal neurons fire when the animal is
      located in a particular subregion of its environment, and in any given
      environment the hippocampal representation is sparse: less than half of the
      neurons in areas CA1 and CA3 are active whereas the rest are essentially silent.
      Here we show that different dynamics govern the evolution of this sparsity in CA1
      and upstream area CA3. CA1, but not CA3, produces twice as many spikes in novel
      compared with familiar environments. This high rate firing continues during sharp
      wave ripple events in a subsequent rest period. The overall CA1 population rate
      declines and the number of active cells decreases as the environment becomes
      familiar and task performance improves, but the decline in rate is not uniform
      across neurons. Instead, the activity of cells with initial peak spatial rates
      above approximately 12 Hz is enhanced, whereas the activity of cells with lower
      initial peak rates is suppressed. The result of these changes is that the active
      CA1 population comes to consist of a relatively small group of cells with strong
      spatial tuning. This process is not evident in CA3, indicating that a region
      specific and long timescale process operates in CA1 to create a sparse, spatially
      informative population of neurons.

PMID- 19109509
TI  - Retinal ganglion cells survive and maintain normal dendritic morphology in a
      mouse model of inherited photoreceptor degeneration.
AB  - Retinitis pigmentosa (RP), a family of inherited disorders characterized by
      progressive photoreceptor death, is a leading cause of blindness with no
      available cure. Despite the genetic heterogeneity underlying the disease, recent
      data on animal models show that the degeneration of photoreceptors triggers
      stereotyped remodeling among their postsynaptic partners. In particular, bipolar
      and horizontal cells might undergo dendritic atrophy and secondary death. The aim
      of this study was to investigate whether or not concomitant changes also occur in
      retinal ganglion cells (RGCs), the only retinal projection neurons to the brain
      and the proposed substrate for various therapeutic approaches for RP. We assessed
      the retention of morphology, overall architecture, and survival of RGCs in a
      mouse model of RP at various stages of the disease. To study the morphology of
      single RGCs, we generated a new mouse line by crossing Thy1-GFP-M mice (Feng et
      al., 2000), which express GFP (green fluorescent protein) in a small number of
      heterogeneous RGCs types, and rd10 mutants, a model of autosomal recessive RP,
      which exhibit a typical rod-cone degeneration (Chang et al., 2002). We show
      remarkable preservation of RGC structure, survival, and projections to higher
      visual centers in the time span from 3 to 9 months of life, well beyond the death
      of photoreceptors. Thus, unlike second-order neurons, RGCs appear as a
      considerably stable population of cells, potentially constituting a favorable
      substrate for restoring vision in RP individuals by means of electronic
      prostheses or direct expression of photosensitive proteins.

PMID- 19109510
TI  - Memory enhancement with event-related stimulation of the rostral intralaminar
      thalamic nuclei.
AB  - The rostral intralaminar thalamic nuclei (ILn) are organized to activate pathways
      originating in medial prefrontal cortex (mPF) that mediate memory-guided
      responding during alert, wakeful states. Previous studies have shown that rostral
      ILn or mPF lesions produce deficits in delayed matching to position (DMTP). Here,
      we manipulated rostral ILn activity in rats by microinjecting drugs or applying
      electrical current and examined effects on DMTP. Inhibiting activity with the
      GABA(A) agonist muscimol impaired DMTP. Decreasing GABA(A) tone with FG-7142 (N
      methyl-beta-carboline-3-carboxamide) improved DMTP at low but not high doses.
      Orexin A, which depolarizes thalamocortical neurons locally within the ILn,
      improved DMTP, whereas the cholinergic agonist carbachol impaired performance at
      the highest dose tested. These drug effects were unaffected by partial mPF
      lesions in a subset of animals. Microinjection results are consistent with an
      inverted-U relationship between thalamic activity and DMTP. This relationship was
      confirmed by event-related electrical stimulation, which produced improvement at
      low stimulation currents and impairment at higher currents. Electrical
      stimulation affected DMTP when applied at the start of the memory delay or choice
      response, but not earlier when trials began or the sample lever was presented.
      Our results are consistent with evidence that the rostral ILn play a role in
      retrieval, carrying response-related information across brief memory delays and
      facilitating memory-guided responding. They also provide evidence that treatments
      stimulating rostral ILn activity may be an effective means to enhance working
      memory and related cognitive processes and thus to treat disorders that affect
      these functions.

PMID- 19109511
TI  - Visual activation and audiovisual interactions in the auditory cortex during
      speech perception: intracranial recordings in humans.
AB  - Hemodynamic studies have shown that the auditory cortex can be activated by
      visual lip movements and is a site of interactions between auditory and visual
      speech processing. However, they provide no information about the chronology and
      mechanisms of these cross-modal processes. We recorded intracranial event-related
      potentials to auditory, visual, and bimodal speech syllables from depth
      electrodes implanted in the temporal lobe of 10 epileptic patients (altogether
      932 contacts). We found that lip movements activate secondary auditory areas,
      very shortly (approximately equal to 10 ms) after the activation of the visual
      motion area MT/V5. After this putatively feedforward visual activation of the
      auditory cortex, audiovisual interactions took place in the secondary auditory
      cortex, from 30 ms after sound onset and before any activity in the polymodal
      areas. Audiovisual interactions in the auditory cortex, as estimated in a linear
      model, consisted both of a total suppression of the visual response to lipreading
      and a decrease of the auditory responses to the speech sound in the bimodal
      condition compared with unimodal conditions. These findings demonstrate that
      audiovisual speech integration does not respect the classical hierarchy from
      sensory-specific to associative cortical areas, but rather engages multiple cross
      modal mechanisms at the first stages of nonprimary auditory cortex activation.

PMID- 19109512
TI  - Mesolimbic functional magnetic resonance imaging activations during reward
      anticipation correlate with reward-related ventral striatal dopamine release.
AB  - The dopaminergic mechanisms that control reward-motivated behavior are the
      subject of intense study, but it is yet unclear how, in humans, neural activity
      in mesolimbic reward-circuitry and its functional neuroimaging correlates are
      related to dopamine release. To address this question, we obtained functional
      magnetic resonance imaging (fMRI) measures of reward-related neural activity and
      [(11)C]raclopride positron emission tomography measures of dopamine release in
      the same human participants, while they performed a delayed monetary incentive
      task. Across the cohort, a positive correlation emerged between neural activity
      of the substantia nigra/ventral tegmental area (SN/VTA), the main origin of
      dopaminergic neurotransmission, during reward anticipation and reward-related
      [(11)C]raclopride displacement as an index of dopamine release in the ventral
      striatum, major target of SN/VTA dopamine neurons. Neural activity in the ventral
      striatum/nucleus accumbens itself also correlated with ventral striatal dopamine
      release. Additionally, high-reward-related dopamine release was associated with
      increased activation of limbic structures, such as the amygdala and the
      hippocampus. The observed correlations of reward-related mesolimbic fMRI
      activation and dopamine release provide evidence that dopaminergic
      neurotransmission plays a quantitative role in human mesolimbic reward
      processing. Moreover, the combined neurochemical and hemodynamic imaging approach
      used here opens up new perspectives for the investigation of molecular mechanisms
      underlying human cognition.

PMID- 19109514
TI  - Defining and classifying cancer cachexia: a proposal by the SCRINIO Working
      Group.
AB  - BACKGROUND: Although cancer cachexia is widely diffuse in the cancer patient
      population, there is no objective definition and classification of this syndrome.
      The purpose of this study is to propose a simple and quick classification that
      relies on the severity of the body weight loss and presence/absence of symptoms
      that are associated with cancer cachexia. METHODS: The authors used a database of
      an ongoing multicenter prospective investigation on the screening of the
      nutrition risk of 1307 cancer outpatients from different (mainly Italian)
      university or scientific institutes or hospitals. The database included
      demographic, oncologic, clinical, and nutrition data. The patients were divided
      into 4 classes based on combinations of body weight loss (< 10%, precachexia; >
      or = 10%, cachexia) and the presence/absence of at least 1 symptom of anorexia,
      fatigue, or early satiation. The authors verified statistically whether these 4
      classes were associated with the distribution of main clinical, nutrition, and
      oncologic variables, after adjustment for treatment status, by using the Cochrane
      Mantel-Hanszel test for count data and ANOVA for continuous data. RESULTS: Moving
      from "asymptomatic precachexia" (class 1) to "symptomatic cachexia" (class 4),
      there were statistically significant trends (P < .0001) in the percentage of
      gastrointestinal vs nongastrointestinal tumors, severity of cancer stage,
      percentage of weight loss, number of symptoms per patient, Eastern Cooperative
      Oncology Group (ECOG) performance status, and nutritional risk score.
      CONCLUSIONS: The statistical analysis has validated the classification by
      identifying stages with different severity of cachexia. This classification could
      be adopted within a comprehensive oncologic approach to the weight-losing
      patients, until more specific diagnostic techniques are available in clinical
      practice.

PMID- 19109513
TI  - Relationship of striatal dopamine synthesis capacity to age and cognition.
AB  - Past research has demonstrated that performance on frontal lobe-dependent tasks
      is associated with dopamine system integrity and that various dopamine system
      deficits occur with aging. The positron emission tomography (PET) radiotracer 6
      [(18)F]fluoro-l-m-tyrosine (FMT) is a substrate of the dopamine-synthesizing
      enzyme, aromatic amino acid decarboxylase (AADC). Studies using 6
      [(18)F]fluorodopa (FDOPA) (another AADC substrate) to measure how striatal PET
      signal and age relate have had inconsistent outcomes. The varying results occur
      in part from tracer processing that renders FDOPA signal subject to aspects of
      postrelease metabolism, which may themselves change with aging. In contrast, FMT
      remains a purer measure of AADC function. We used partial volume-corrected FMT
      PET scans to measure age-related striatal dopamine synthesis capacity in 21 older
      (mean, 66.9) and 16 younger (mean, 22.8) healthy adults. We also investigated how
      striatal FMT signal related to a cognitive measure of frontal lobe function.
      Older adults showed significantly greater striatal FMT signal than younger
      adults. Within the older group, FMT signal in dorsal caudate (DCA) and dorsal
      putamen was greater with age, suggesting compensation for deficits elsewhere in
      the dopamine system. In younger adults, FMT signal in DCA was lower with age,
      likely related to ongoing developmental processes. Younger adults who performed
      worse on tests of frontal lobe function showed greater FMT signal in right DCA,
      independent of age effects. Our data suggest that higher striatal FMT signal
      represents nonoptimal dopamine processing. They further support a relationship
      between striatal dopamine processing and frontal lobe cognitive function.

PMID- 19109515
TI  - Endothelial dysfunction and pathophysiological correlates in atrial fibrillation.
AB  - Endothelial dysfunction (ED) increases oxidative stress and proinflammatory
      agents, and impairs nitric oxide (NO)-dependent vasorelaxation. Atrial
      fibrillation (AF) is a risk factor for ED as documented by (1) impaired
      acetylcholine-mediated blood flow increase; (2) reduced plasma nitrite/nitrate
      levels; (3) additive impairment of flow-mediated dilatation by comorbidities
      causing ED; and (4) efficacy of cardioversion. Several possible mechanisms
      sustain the AF-ED association: (1) An impaired rheology. Endothelial NO release
      is tightly regulated by laminar shear stress and AF induces a turbulent flow
      which may impair arterial vessel distension and responsiveness. Specifically,
      Ca(2+) elicits NO synthase (eNOS) activation, and shear stress application to
      endothelial cells increases intracellular Ca(2+) primarily in response to regular
      pulsatile flow at a rate higher than that observed in the presence of oscillatory
      pulsatile flow. (2) The atrium activity on arterial vessels. The left atrium
      produces NO and may serve as an endocrine organ releasing nitroso compounds. A
      disorganised atrial contraction markedly reduces eNOS expression. (3) AF induces
      atrial inflammation and elevation of C reactive protein and cytokines, exerting a
      proinflammatory activity on endothelial cells. (4) Systemic factors such as the
      renin-angiotensin system (RAS) may be prominent. In fact, RAS and inflammation
      reciprocally "cross-talk". Angiotensin II increases atrial cell death and RAS
      contributes to myocardial and vascular oxidative stress in AF. RAS inhibition
      prevents AF. Important clinical correlates of ED in AF patients are muscle
      underperfusion, premature lactic acidosis and ergoreflex oversignalling during
      physical activity. This review focuses on the evidence of an association of AF
      with ED, the possible underlying mechanisms and the pathophysiological
      correlates.

PMID- 19109516
TI  - Cutaneous vasculitis rash due to bacterial endocarditis.

PMID- 19109517
TI  - Significant QT-interval prolongation in pulmonary embolism--evidence for
      mechanoelectrical feedback.

PMID- 19109518
TI  - Heart failure in the UK.

PMID- 19109519
TI  - The future of atrial fibrillation ablation: new technologies and indications:
      atrial fibrillation.

PMID- 19109520
TI  - Echocardiography in the emergency room: non-invasive imaging.

PMID- 19109521
TI  - MAP kinase phosphatase-1: a link between cell signaling and histone
      phosphorylation. Focus on "Histone H3 as a novel substrate for MAP kinase
      phosphatase-1".

PMID- 19109522
TI  - Calpain-1 is required for hydrogen peroxide-induced myotube atrophy.
AB  - Recent reports suggest numerous roles for cysteine proteases in the progression
      of skeletal muscle atrophy due to disuse or disease. Nonetheless, a specific
      requirement for these proteases in the progression of skeletal muscle atrophy has
      not been demonstrated. Therefore, this investigation determined whether calpains
      or caspase-3 is required for oxidant-induced C2C12 myotube atrophy. We
      demonstrate that exposure to hydrogen peroxide (25 microM H2O2) induces myotube
      oxidative damage and atrophy, with no evidence of cell death. Twenty-four hours
      of exposure to H2O2 significantly reduced both myotube diameter and the abundance
      of numerous proteins, including myosin (-81%), alpha-actinin (-40%), desmin (
      79%), talin (-37%), and troponin I (-80%). Myotube atrophy was also characterized
      by increased cleavage of the cysteine protease substrate alphaII-spectrin
      following 4 h and 24 h of H2O2 treatment. This degradation was blocked by
      administration of the protease inhibitor leupeptin (10 microM). Using small
      interfering RNA transfection of mature myotubes against the specific proteases
      calpain-1, calpain-2, and caspase-3, we demonstrated that calpain-1 is required
      for H2O2-induced myotube atrophy. Collectively, our data provide the first
      evidence for an absolute requirement for calpain-1 in the development of skeletal
      muscle myotube atrophy in response to oxidant-induced cellular stress.

PMID- 19109523
TI  - Tumor necrosis factor-{alpha} downregulates intestinal NHE8 expression by
      reducing basal promoter activity.
AB  - NHE8 transporter is a member of the sodium/hydrogen exchanger (NHE) family. This
      transporter protein is expressed at the apical membrane of epithelial cells of
      kidney and intestine and contributes to vectorial Na(+) transport in both
      tissues. Although NaCl absorption has been shown to be reduced in diarrhea
      associated with colitis and enteritis, little is known about the role of
      Na(+)/H(+) exchange and the involvement of NHE isoforms in the pathogenesis of
      inflammatory disorders and the mechanism of inflammation-associated diarrhea.
      This study investigated the role of NHE8 in the setting of inflammatory states.
      Jejunal mucosa was harvested from trinitrobenzene sulfonic acid (TNBS) colitis
      rats or lipopolysaccharide (LPS) rats for RNA extraction and brush-border
      membrane protein purification. The human NHE8 gene promoter was cloned from human
      genomic DNA and characterized in Caco-2 cells. The promoter was further used to
      study the mechanisms of TNF-alpha-mediated NHE8 expression downregulation in Caco
      2 cells. Results from Western blot and real-time PCR indicated that NHE8 protein
      and mRNA were significantly reduced in TNBS rats and LPS rats. In Caco-2 cells,
      TNF-alpha produces similar reduction levels in the endogenous NHE8 mRNA
      expression observed in our in vivo studies. The downregulation of NHE8 expression
      mediated by TNF-alpha could be blocked by transcription inhibitor actinomycin D,
      suggesting the involvement of transcriptional regulation. Further studies
      indicated that the human NHE8 gene transcription could be activated by Sp3
      transcriptional factor, and TNF-alpha inhibits human NHE8 expression by reducing
      Sp3 interaction at the minimal promoter region of the human NHE8 gene. In
      conclusion, our studies suggest that TNF-alpha decreases NHE8 expression in
      inflammation induced by TNBS and LPS, which may contribute to the diarrhea
      associated with inflammation.

PMID- 19109524
TI  - Hyperosmotic stress induces Rho/Rho kinase/LIM kinase-mediated cofilin
      phosphorylation in tubular cells: key role in the osmotically triggered F-actin
      response.
AB  - Hyperosmotic stress induces cytoskeleton reorganization and a net increase in
      cellular F-actin, but the underlying mechanisms are incompletely understood.
      Whereas de novo F-actin polymerization likely contributes to the actin response,
      the role of F-actin severing is unknown. To address this problem, we investigated
      whether hyperosmolarity regulates cofilin, a key actin-severing protein, the
      activity of which is inhibited by phosphorylation. Since the small GTPases Rho
      and Rac are sensitive to cell volume changes and can regulate cofilin
      phosphorylation, we also asked whether they might link osmostress to cofilin.
      Here we show that hyperosmolarity induced rapid, sustained, and reversible
      phosphorylation of cofilin in kidney tubular (LLC-PK1 and Madin-Darby canine
      kidney) cells. Hyperosmolarity-provoked cofilin phosphorylation was mediated by
      the Rho/Rho kinase (ROCK)/LIM kinase (LIMK) but not the Rac/PAK/LIMK pathway,
      because 1) dominant negative (DN) Rho and DN-ROCK but not DN-Rac and DN-PAK
      inhibited cofilin phosphorylation; 2) constitutively active (CA) Rho and CA-ROCK
      but not CA-Rac and CA-PAK induced cofilin phosphorylation; 3) hyperosmolarity
      induced LIMK-2 phosphorylation, and 4) inhibition of ROCK by Y-27632 suppressed
      the hypertonicity-triggered LIMK-2 and cofilin phosphorylation.We thenexamined
      whether cofilin and its phosphorylation play a role in the hypertonicity
      triggered F-actin changes. Downregulation of cofilin by small interfering RNA
      increased the resting F-actin level and eliminated any further rise upon
      hypertonic treatment. Inhibition of cofilin phosphorylation by Y-27632 prevented
      the hyperosmolarity-provoked F-actin increase. Taken together, cofilin is
      necessary for maintaining the osmotic responsiveness of the cytoskeleton in
      tubular cells, and the Rho/ROCK/LIMK-mediated cofilin phosphorylation is a key
      mechanism in the hyperosmotic stress-induced F-actin increase.

PMID- 19109525
TI  - Molecular beacons can assess changes in expression and 3'-polyadenylation of
      human eNOS mRNA.
AB  - The endothelium plays an essential role in maintaining vascular homeostasis, and
      it fulfills this role by modulating intracellular signaling and gene expression
      in response to chemical and mechanical stimuli. Assessing changes in endothelial
      gene expression is essential to understanding how physiological and
      pathophysiological processes modulate vascular homeostasis. Here we describe the
      use of molecular beacons to rapidly and quantitatively assess expression and 3'
      polyadenylation of a gene that is important for vascular homeostasis, endothelial
      nitric oxide synthase (eNOS). Single- and dual-fluorescence resonance energy
      transfer (FRET) molecular beacon hybridization assays were developed to measure
      changes in mRNA levels and 3'-polyadenylation, respectively, in primary human
      endothelial cell cultures subjected to laminar shear stress or statin treatment.
      Optimized beacon hybridization assays took approximately 15 min to perform, and
      eNOS mRNA levels were validated by quantitative real-time RT-PCR. Competitive
      inhibition assays and posttranscriptional silencing of eNOS expression were used
      to verify the specificity of molecular beacon fluorescence. Finally, the dual
      FRET method was used to assess eNOS polyadenylation in tissues isolated from mice
      subjected to exercise training. These data demonstrate that molecular beacons can
      be used to rapidly and efficiently measure endothelial gene expression and 3'
      polyadenylation. This approach could easily be adapted for studies of other
      endothelial genes and has promise for applications in live endothelial cells.

PMID- 19109526
TI  - Overexpression of Galgt2 in skeletal muscle prevents injury resulting from
      eccentric contractions in both mdx and wild-type mice.
AB  - The cytotoxic T cell (CT) GalNAc transferase, or Galgt2, is a UDP-GalNAc:beta1,4
      N-acetylgalactosaminyltransferase that is localized to the neuromuscular synapse
      in adult skeletal muscle, where it creates the synaptic CT carbohydrate antigen
      {GalNAcbeta1,4[NeuAc(orGc)alpha2, 3]Galbeta1,4GlcNAcbeta-}. Overexpression of
      Galgt2 in the skeletal muscles of transgenic mice inhibits the development of
      muscular dystrophy in mdx mice, a model for Duchenne muscular dystrophy. Here, we
      provide physiological evidence as to how Galgt2 may inhibit the development of
      muscle pathology in mdx animals. Both Galgt2 transgenic wild-type and mdx
      skeletal muscles showed a marked improvement in normalized isometric force during
      repetitive eccentric contractions relative to nontransgenic littermates, even
      using a paradigm where nontransgenic muscles had force reductions of 95% or more.
      Muscles from Galgt2 transgenic mice, however, showed a significant decrement in
      normalized specific force and in hindlimb and forelimb grip strength at some
      ages. Overexpression of Galgt2 in muscles of young adult mdx mice, where Galgt2
      has no effect on muscle size, also caused a significant decrease in force drop
      during eccentric contractions and increased normalized specific force. A
      comparison of Galgt2 and microdystrophin overexpression using a therapeutically
      relevant intravascular gene delivery protocol showed Galgt2 was as effective as
      microdystrophin at preventing loss of force during eccentric contractions. These
      experiments provide a mechanism to explain why Galgt2 overexpression inhibits
      muscular dystrophy in mdx muscles. That overexpression also prevents loss of
      force in nondystrophic muscles suggests that Galgt2 is a therapeutic target with
      broad potential applications.

PMID- 19109527
TI  - Simvastatin enhances bone marrow stromal cell differentiation into endothelial
      cells via notch signaling pathway.
AB  - Bone marrow stromal cells (BMSCs) are capable of differentiating into multiple
      cell lineages including endothelial cells. Simvastatin, an HMG-CoA reductase
      inhibitor that is used as a cholesterol-lowering agent, promotes endothelial
      differentiation from epithelial progenitor cells (EPC). The Notch signaling
      pathway, which plays a key role in multiple cell functions such as
      differentiation, proliferation, and apoptosis, can be regulated by simvastatin.
      Therefore, we examined the effect of simvastatin on BMSC differentiation into
      endothelial cells and the underlying mechanisms involved in this process. We
      observed that simvastatin stimulation of rat BMSCs resulted in significantly
      increased expression of endothelial-specific genes and proteins, including von
      Willebrand factor (vWF), CD31, vascular endothelial-cadherin (VE-cadherin),
      vascular endothelial growth factor receptor-2 (VEGFR2, Flk-1), and VEGF receptor
      1 (VEGFR-1, Flt-1). Simvastatin also significantly increased capillary tubelike
      formation of the BMSCs. In addition, the intracellular cleavage of Notch (NICD)
      was markedly enhanced by simvastatin in BMSCs. Incubation of BMSCs with a gamma
      secretase inhibitor, or Notch1 small interfering RNA (siRNA) that significantly
      inhibited the formation of NICD, blocked the expression of endothelial-specific
      markers in BMSCs and their differentiation into functional endothelial cells.
      These data suggest that simvastatin induces rat BMSCs differentiation into
      endothelial cells via a Notch signaling pathway.

PMID- 19109528
TI  - Autonomic nervous system regulates secretion of anti-inflammatory prohormone SMR1
      from rat salivary glands.
AB  - The autonomic nervous system regulates the secretion of bioactive proteins and
      peptides from salivary glands that can be important in systemic physiological
      responses. The prohormone submandibular rat-1, which is highly expressed in rat
      submandibular glands, can be cleaved to produce polypeptides with analgesic and
      anti-inflammatory activities. Human genes related to submandibular rat-1 have
      conserved biological functions and are potentially important in pain suppression,
      erectile function, and inflammation. In this study we describe the differential
      expression and posttranslational modification of submandibular rat-1 protein in
      salivary glands, the urogenital tract, lung, blood, and saliva in male Sprague
      Dawley and Brown Norway rats. Submandibular rat-1 protein is secreted into saliva
      after the administration of beta-adrenergic or cholinergic agonists. Removal of
      the sympathetic ganglion that innervates the salivary glands results in increased
      levels of submandibular rat-1 protein in salivary glands. The secretion of
      submandibular rat-1 in response to physiological stress may provide a large pool
      of submandibular rat-1-derived peptide products that can promote analgesia and
      decrease inflammation locally and systemically. This pathway may be conserved
      among mammals and may constitute an important anti-inflammatory and analgesic
      response to stress.

PMID- 19109529
TI  - A defining analysis of the life and death dyad: paving the way for an ethical
      debate.
AB  - We discuss the meaning of "being alive" and "being dead." Our primary aim is to
      pave the way for a sound and accurate ethical debate concerning these two
      concepts. In particular, we analyze a metabolic approach and a genetic one and
      discuss the reasons for their failure to constitute a good starting point for
      successive debates. We argue that any ethical or social discussion of topics
      involving life and death must introduce cultural constructs such as, on the one
      hand, the concept of clinical death and, on the other hand, the concept of
      existence. We argue that these two cultural constructs, although consistent with
      biomedical knowledge, cannot be ontologically grounded in it. To conclude, we
      apply our findings to the case of human embryos.

PMID- 19109530
TI  - Medical ethics needs a new view of autonomy.
AB  - The notion of autonomy commonly employed in medical ethics literature and
      practices is inadequate on three fronts: it fails to properly identify
      nonautonomous actions and choices, it gives a false account of which features of
      actions and choices makes them autonomous or nonautonomous, and it provides no
      grounds for the moral requirement to respect autonomy. In this paper I offer a
      more adequate framework for how to think about autonomy, but this framework does
      not lend itself to the kinds of practical application assumed in medical ethics.
      A general problem then arises: the notion of autonomy used in medical ethics is
      conceptually inadequate, but conceptually adequate notions of autonomy do not
      have the practical applications that are the central concern of medical ethics.
      Thus, a revision both of the view of autonomy and the practice of "respect for
      autonomy" are in order.

PMID- 19109531
TI  - Incidence of subsequent injury to either knee within 5 years after anterior
      cruciate ligament reconstruction with patellar tendon autograft.
AB  - BACKGROUND: The risk of subsequent anterior cruciate ligament injury to either
      knee after surgery based on sex, age, and activity has not been extensively
      studied. HYPOTHESES: Women have a higher incidence of anterior cruciate ligament
      injury to the contralateral knee after surgery than men but do not have a
      difference in injuries to the reconstructed knee. Young, competitive athletes
      have a higher incidence of injury than older patients. The time to return to full
      activities does not affect injury rate. STUDY DESIGN: Cohort study (prognosis);
      Level of evidence, 2. METHODS: The authors prospectively followed 1820 patients
      after primary anterior cruciate ligament reconstruction to determine if patients
      suffered an injury to either knee within 5 years after surgery. Subsequent injury
      was evaluated based on sex, age, and activity level. RESULTS: Minimum 5-year
      follow-up was obtained on 1415 patients (78%). Seventy-five patients (5.3%) had
      an injury to the contralateral knee, and 61 patients (4.3%) suffered an injury to
      the reconstructed knee (P = .2185). Women suffered more injuries (7.8%) to the
      contralateral normal knee than men (3.7%; P < .001) but not more injuries to the
      reconstructed knee (4.3% vs 4.1%; P = .5543). The risk of subsequent injury to
      either knee was 17% for patients <18 years old, 7% for patients aged 18 to 25
      years, and 4% for patients older than 25 years. There was no difference in injury
      rate between patients who returned before and after 6 months postoperatively.
      CONCLUSION: Women have a higher incidence of anterior cruciate ligament injury to
      the contralateral knee than men after reconstruction. The incidence of injury to
      either knee after reconstruction is associated with younger age and higher
      activity level, but returning to full activities before 6 months postoperatively
      does not increase the risk of subsequent injury.

PMID- 19109532
TI  - Mutual partner violence: mental health symptoms among female and male victims in
      four racial/ethnic groups.
AB  - This study examines racial/ethnic and sex differences in the prevalence of mutual
      intimate partner violence (IPV) and mental health symptoms. The authors asked 676
      university students in heterosexual relationships if they had experienced IPV,
      coercive victimization, and/or perpetration as well as symptoms of depression,
      anxiety, hostility, and somatization. Analyses were conducted separately for
      female and male respondents in four racial/ethnic groups, totaling eight groups
      (female and male groups each for African Americans, Asian Americans, Latinos, and
      European Americans). Men, as compared to women, reported stronger correlations
      between IPV perpetration and IPV victimization, with Asian American men reporting
      the highest associations of any group. Additionally, experiencing higher partner
      and coercive violence was significantly related to increased mental health
      symptoms for all groups except Asian American men. Taken together, these findings
      suggest that the majority of couples experience mutual violence that elicits
      mental health problems for both members of the couple.

PMID- 19109533
TI  - Assessing the anomalous research on Hispanic victimization: a methodological
      critique of a victimological enigma.
AB  - This article provides an overview and critique of the research on Hispanic
      victimization. Analyses of data gathered prior to the mid- to late 1990s
      consistently show Hispanics were victimized at disproportionately high rates, but
      numerous recent studies indicate Hispanics were not victimized at
      disproportionately high rates. Given that research has consistently shown
      victimization rates are highest among the poor and that Hispanics are a
      disproportionately impoverished demographic, the findings that Hispanics were not
      victimized at disproportionately high rates are enigmatic. It is suggested that
      social changes in the United States-specifically, the increase in the portion of
      the Hispanic population composed of immigrants and the development of Latin
      American enclaves-have reduced the efficacy of conventional methodological
      tactics and that the recent findings on Hispanic victimization were affected by
      the inadequate representation of disadvantaged Hispanics (especially immigrants
      and migrants) in survey studies and the reluctance of Hispanic immigrants to
      report crimes to the police. Finally, it is argued that the practice of
      conducting analyses of ethnic variation in victimization wherein all non
      Hispanics (Asians, Blacks, Native Americans, and Whites) are amalgamated into a
      single category and compared with Hispanics has generated misleading results.

PMID- 19109534
TI  - Experiences of sexual coercion among adolescent women: qualitative findings from
      Rakai district, Uganda.
AB  - Limited data from low-income countries are available on the continuum of coercive
      experiences, the contexts in which they occur, and how adolescent women perceive
      and respond to coercion. This article presents results from focus group
      discussions and in-depth interviews with pregnant and never pregnant sexually
      active female adolescents, aged 15 to 17, residing in Rakai District, Uganda, to
      examine sexual coercion, its context, and the links between coercion and
      adolescent reproductive health outcomes, including early sexual debut and
      pregnancy. Informants described multiple forms of sexual coercion, including
      coerced or forced intercourse, unwanted sexual touching, verbal harassment, and
      transactional sex. Sexual coercion was perceived to be a normal part of intimate
      relationships; in particular, informants felt that a woman's lack of decision
      making authority, including choices on sexual encounters, was implicit to
      marriage. This information may help violence prevention programs develop a range
      of strategies for addressing sexual coercion among adolescents.

PMID- 19109535
TI  - Thin skin: the cortical signature of prodromal AD?

PMID- 19109537
TI  - Quantifying the risk of neurodegenerative disease in idiopathic REM sleep
      behavior disorder.
AB  - OBJECTIVE: Idiopathic REM sleep behavior disorder (RBD) is a potential
      preclinical marker for the development of neurodegenerative diseases,
      particularly Parkinson disease (PD) and Lewy body dementia. However, the long
      term risk of developing neurodegeneration in patients with idiopathic RBD has not
      been established. Obtaining an accurate picture of this risk is essential for
      counseling patients and for development of potential neuroprotective therapies.
      METHODS: We conducted a follow-up study of all patients seen at the sleep
      disorders laboratory at the Hopital du Sacre Coeur with a diagnosis of idiopathic
      RBD. Diagnoses of parkinsonism and dementia were defined according to standard
      criteria. Survival curves were constructed to estimate the 5-, 10-, and 12-year
      risk of developing neurodegenerative disease. RESULTS: Of 113 patients, 93 (82%)
      met inclusion criteria. The mean age of participants was 65.4 years and 75
      patients (80.4%) were men. Over the follow-up period, 26/93 patients developed a
      neurodegenerative disorder. A total of 14 patients developed PD, 7 developed Lewy
      body dementia, 4 developed dementia that met clinical criteria for AD, and 1
      developed multiple system atrophy. The estimated 5-year risk of neurodegenerative
      disease was 17.7%, the 10-year risk was 40.6%, and the 12-year risk was 52.4%.
      CONCLUSIONS: Although we have found a slightly lower risk than other reports, the
      risk of developing neurodegenerative disease in idiopathic REM sleep behavior
      disorder is substantial, with the majority of patients developing Parkinson
      disease and Lewy body dementia.

PMID- 19109536
TI  - The cortical signature of prodromal AD: regional thinning predicts mild AD
      dementia.
AB  - OBJECTIVE: We previously used exploratory analyses across the entire cortex to
      determine that mild Alzheimer disease (AD) is reliably associated with a cortical
      signature of thinning in specific limbic and association regions. Here we
      investigated whether the cortical signature of AD-related thinning is present in
      individuals with questionable AD dementia (QAD) and whether a greater degree of
      regional cortical thinning predicts mild AD dementia. METHODS: Participants
      included 49 older adults with mild impairment consistent with mild cognitive
      impairment (Clinical Dementia Rating [CDR] = 0.5) at the time of structural MRI
      scanning. Cortical thickness was measured in nine regions of interest (ROIs)
      identified previously from a comparison of patients with mild AD and controls.
      RESULTS: Longitudinal clinical follow-up revealed that 20 participants converted
      to mild AD dementia (progressors) while 29 remained stable (nonprogressors)
      approximately 2.5 years after scanning. At baseline, QAD participants showed a
      milder degree of cortical thinning than typically seen in mild AD, and CDR Sum-of
      Boxes correlated with thickness in temporal and parietal ROIs. Compared to
      nonprogressors, progressors showed temporal and parietal thinning. Using receiver
      operating characteristic curves, the thickness of an aggregate measure of these
      regions predicted progression to mild AD with 83% sensitivity and 65%
      specificity. CONCLUSIONS: Thinning in specific cortical areas known to be
      affected by Alzheimer disease (AD) is detectable in individuals with questionable
      AD dementia (QAD) and predicts conversion to mild AD dementia. This method could
      be useful for identifying individuals at relatively high risk for imminent
      progression from QAD to mild AD dementia, which may be of value in clinical
      trials.

PMID- 19109538
TI  - The metabolic syndrome is associated with a higher resistance to intravenous
      thrombolysis for acute ischemic stroke in women than in men.
AB  - BACKGROUND AND PURPOSE: The metabolic syndrome (MetS) might confer a higher
      resistance to intravenous thrombolysis in acute middle cerebral artery (MCA)
      ischemic stroke. MetS increases the risk of stroke in women to a greater extent
      than in men. We aimed to investigate whether there might be sex differences in
      the impact of MetS on the response to intravenous thrombolysis for acute MCA
      ischemic stroke. METHODS: We prospectively studied consecutive ischemic stroke
      patients, treated with intravenous tissue-type plasminogen activator according to
      SITS-MOST criteria, with an MCA occlusion on prebolus transcranial Doppler
      examination. Resistance to thrombolysis was defined as the absence of complete
      MCA recanalization 24 hours after tissue-type plasminogen activator infusion by
      transcranial Doppler criteria. MetS was diagnosed according to the criteria
      established by the American Heart Association/National Heart, Lung, and Blood
      Institute 2005 statement. RESULTS: A total of 125 patients (75 men, 50 women;
      mean age, 67.6+/-11 years) were included. MetS was diagnosed in 76 (61%)
      patients. Resistance to clot lysis at 24 hours was observed in 53 (42%) patients.
      Two multivariate-adjusted, logistic-regression models identified that MetS was
      associated with a higher resistance to tissue-type plasminogen activator,
      independently of other significant baseline variables (odds ratio=9.8; 95% CI,
      3.5 to 27.8; P=0.0001) and of the individual components of the MetS. The MetS was
      associated with a significantly higher odds of resistance to thrombolysis in
      women (odds ratio=17.5; 95% CI, 1.9 to 163.1) than in men (odds ratio=5.1; 95%
      CI, 1.6 to 15.6; P for interaction=0.0004). CONCLUSIONS: The effect of MetS on
      the resistance to intravenous thrombolysis for acute MCA ischemic stroke appears
      to be more pronounced in women than in men.

PMID- 19109540
TI  - Costs of stroke using patient-level data: a critical review of the literature.
AB  - BACKGROUND AND PURPOSE: With decision-analytic models becoming more popular to
      assess the cost-effectiveness of health care interventions, the need for robust
      estimates on the costs of cerebrovascular disease is paramount. This study
      reports the results from a literature review of the costs of cerebrovascular
      diseases, and assesses the quality of the published evidence against a set of
      defined criteria. METHODS: A broad literature search was conducted. Those studies
      reporting mean/median costs of cerebrovascular diseases derived from patient
      level data in a developed country setting were included. Data were abstracted
      using standardized reporting forms and assessed against 4 predefined criteria:
      use of adequate methodologies, use of a population-based study, inclusion of
      premorbid resource use, and reporting of costs by different patient subgroups.
      RESULTS: A total of 120 cost studies were identified. The cost estimates of
      stroke were compared by taking into account the effects of inflation and price
      differentials between countries. Average costs of stroke ranged from $468 to $146
      149. Differences in costs were also found within country, with estimates in the
      USA varying 20-fold. Although the costing methodologies used were generally
      appropriate, only 5 studies were based on population-based studies, which are the
      gold standard study design when comparing incidence, outcome, and costs.
      CONCLUSIONS: This review showed large variations in the costs of stroke, mainly
      attributable to differences in the populations studied, methods, and cost
      categories included. The wide range of cost estimates could lead to selection
      bias in secondary health economic analyses, with authors including those costs
      that are more likely to produce the desired results.

PMID- 19109539
TI  - Pharmacogenomic effects of apolipoprotein e on intracerebral hemorrhage.
AB  - BACKGROUND AND PURPOSE: The purpose of the study was to evaluate the effect of
      APOE genotype and the feasibility of administering an apolipoprotein E-mimetic
      therapeutic to modify outcomes in a murine model of intracerebral hemorrhage.
      METHODS: Intracerebral hemorrhage was induced via stereotactic injection of 0.1 U
      Clostridial collagenase into the left basal ganglia of wild-type and
      apolipoprotein-E targeted-replacement mice, consisting of either homozygous 3/3
      or 4/4 genotypes. Animals were randomized to receive either vehicle or
      apolipoprotein E-mimetic peptide. Outcomes included functional neurological tests
      (21-point neuroseverity score and Rotorod latency) over the initial 7 days after
      injury, radiographic and histological hemorrhage size at 3 and 7 days, brain
      water content for cerebral edema at 24 hours, and quantitative polymerase chain
      reaction for inflammatory markers at 6, 24, and 48 hours. RESULTS: Apolipoprotein
      E targeted-replacement mice consisting of homozygous 3/3 demonstrated superior
      neuroseverity scores and Rotorod latencies over the first 3 days after
      intracerebral hemorrhage, decreased cerebral edema at 24 hours, and reduced
      upregulation of IL-6 and endothelial nitric oxide synthase at 6 hours when
      compared to their apolipoprotein-E targeted-replacement mice consisting of
      homozygous 4/4 counterparts. After intravenous administration of 1 mg/kg
      apolipoprotein E-mimetic peptide, both wild-type and apolipoprotein-E targeted
      replacement mice consisting of homozygous 4/4 exhibited improved functional
      outcomes over 7 days after intracerebral hemorrhage, less edema at 24 hours, and
      reduced upregulation of IL-6 and endothelial nitric oxide synthase when compared
      to mice that did not receive the peptide. CONCLUSIONS: Our data indicate that
      APOE genotype influences neurological outcome after intracerebral hemorrhage in a
      murine model. In particular APOE4 is associated with poor functional outcome and
      increased cerebral edema. Additionally, this outcome can be modified by the
      addition of an apolipoprotein E mimetic-peptide, COG1410.

PMID- 19109541
TI  - Microarray RNA expression analysis of cerebral white matter lesions reveals
      changes in multiple functional pathways.
AB  - BACKGROUND AND PURPOSE: White matter lesions (WML) in brain aging are linked to
      dementia and depression. Ischemia contributes to their pathogenesis but other
      mechanisms may contribute. We used RNA microarray analysis with functional
      pathway grouping as an unbiased approach to investigate evidence for additional
      pathogenetic mechanisms. METHODS: WML were identified by MRI and pathology in
      brains donated to the Medical Research Council Cognitive Function and Ageing
      Study Cognitive Function and Aging Study. RNA was extracted to compare WML with
      nonlesional white matter samples from cases with lesions (WM[L]), and from cases
      with no lesions (WM[C]) using RNA microarray and pathway analysis. Functional
      pathways were validated for selected genes by quantitative real-time polymerase
      chain reaction and immunocytochemistry. RESULTS: We identified 8 major pathways
      in which multiple genes showed altered RNA transcription (immune regulation, cell
      cycle, apoptosis, proteolysis, ion transport, cell structure, electron transport,
      metabolism) among 502 genes that were differentially expressed in WML compared to
      WM[C]. In WM[L], 409 genes were altered involving the same pathways. Genes
      selected to validate this microarray data all showed the expected changes in RNA
      levels and immunohistochemical expression of protein. CONCLUSIONS: WML represent
      areas with a complex molecular phenotype. From this and previous evidence, WML
      may arise through tissue ischemia but may also reflect the contribution of
      additional factors like blood-brain barrier dysfunction. Differential expression
      of genes in WM[L] compared to WM[C] indicate a "field effect" in the seemingly
      normal surrounding white matter.

PMID- 19109542
TI  - Modified constraint-induced therapy combined with mental practice: thinking
      through better motor outcomes.
AB  - BACKGROUND AND PURPOSE: Modified constraint-induced therapy (mCIT) is an
      outpatient therapy encouraging repetitive, task-specific practice with the
      affected arm. mCIT has shown efficacy in all stages poststroke. Given its
      efficacy when combined with other therapy regimens, the current study examined
      the efficacy of mental practice when combined with mCIT versus mCIT only using
      randomized, controlled methods. METHOD: Ten patients with chronic stroke (7
      males; mean age, 61.4+/-3.02 years; age range, 48 to 79 years; mean time since
      stroke, 28.5 months; range, 13 to 42 months) exhibiting stable, affected arm
      motor deficits were administered mCIT, consisting of: (1) structured therapy
      emphasizing affected arm use in functional activities 3 days/week for 10 weeks;
      and (2) less affected arm restraint 5 days/week for 5 hours. Both of these
      components were administered during a 10-week period. Subjects randomly assigned
      to the mCIT+mental practice experimental condition also received 30-minute mental
      practice sessions provided directly after therapy sessions. These mental practice
      sessions required daily cognitive rehearsal of the activities of daily living
      practiced during mCIT clinical sessions. RESULTS: No pre-existing differences
      were found between groups on any demographic variable or movement scale. All
      subjects exhibited marked reductions in affected arm impairment and functional
      limitation. However, subjects in the mCIT+mental practice group exhibited
      significantly larger changes on both movement measures after intervention: Action
      Research Arm Test, +15.4-point change versus +8.4-point change for mCIT only
      subjects (P<0.001); Fugl-Meyer, +7.8-point change versus +4.1-point change for
      the mCIT only subjects (P=0.01). These changes were sustained 3 months after
      intervention. CONCLUSIONS: mCIT remains a promising motor intervention. However,
      its efficacy appears to be enhanced by use of mental practice provided directly
      after mCIT clinical sessions.

PMID- 19109543
TI  - Arm use after left or right hemiparesis is influenced by hand preference.
AB  - BACKGROUND AND PURPOSE: Despite strong evidence for hand preference and its
      impact on motor performance, its influence on stroke rehabilitation has not been
      routinely considered. Previous research demonstrates that patients with
      hemiparetic stroke use their ipsilesional, nonparetic arm 5 to 6 times more
      frequently than their paretic arm, but it is unknown if such use varies with
      laterality of hemiparesis. The purpose of our study was to determine if the right
      arm is used more frequently in right-handed patients with stroke. METHODS: We
      assessed relative use of the right, left, and both arms with wrist accelerometers
      on patients with unilateral, paretic stroke matched for degree of paresis (12
      with right hemisphere damage, 17 with left hemisphere damage) and 25
      neurologically intact control participants as they performed the Arm Motor
      Ability Test. RESULTS: We showed: (1) ipsilesional arm use was greater after
      right hemisphere damage than left hemisphere damage; (2) the left hemisphere
      damage group used both arms together more often than the right hemisphere damage
      group but less often than the control group; and (3) both stroke groups used
      their contralesional, paretic arm to the same degree. CONCLUSIONS: These findings
      emphasize the influence of hand preference on arm use after stroke for the
      ipsilesional but not the contralesional arm. Although both stroke groups used
      their ipsilesional more than their contralesional arm, the difference was greater
      for the right hemisphere damage group who used their ipsilesional arm 4 times
      more frequently than their contralesional arm, whereas the left hemisphere damage
      group used their ipsilesional arm 2 times more frequently than their
      contralesional arm.

PMID- 19109544
TI  - Association between recent sports activity, sports activity in young adulthood,
      and stroke.
AB  - BACKGROUND AND PURPOSE: Leisure-time physical activity protects from stroke. It
      is insufficiently established whether early lifetime physical activity is
      independently protective and whether some etiologic stroke subgroups particularly
      benefit from physical activity. We tested the hypothesis that both recent and
      early-adulthood sports activities are associated with reduced odds of stroke and
      analyzed their effects in stroke subtypes. METHODS: We performed a case-control
      study of 370 patients with acute stroke or transient ischemic attack (TIA) and
      370 age- and sex-matched control subjects randomly selected from the population
      and assessed recent and young adulthood sports activities and their weekly
      duration in standardized interviews. RESULTS: Recent regular sports activities
      were less often reported by patients (94/370, 25.4%) than by control subjects
      (162/370, 43.8%; P<0.0001). After adjustment for vascular risk factors,
      education, and other factors, recent participation in sports was significantly
      associated with reduced odds of stroke/TIA (odds ratio=0.64; 95% CI, 0.43 to
      0.96). Both groups did not differ with regard to sports activities in young
      adulthood. More control subjects (69/365, 18.9%) than patients (25/361, 6.9%)
      participated in sports recently after not having been active in young adulthood,
      and such a pattern was associated with reduced odds of stroke/TIA in
      multivariable analysis (odds ratio=0.37; 95% CI, 0.21 to 0.85). CONCLUSIONS: Our
      study supports previous results that have shown stroke protection by physical
      activity. Results suggest that continuous lifetime activity or starting
      activities during later adulthood is required to reduce stroke risk.

PMID- 19109545
TI  - Isolated nodular infarction.
AB  - BACKGROUND AND PURPOSE: Isolated nodular infarction has rarely been described in
      human. The purpose of this study is to report clinical and laboratory findings of
      isolated nodular infarction. METHODS: Eight patients with isolated nodular
      infarction were recruited from 6 hospitals in Korea. All patients underwent a
      complete and standardized neurotological evaluation including ocular torsion,
      bithermal caloric tests, and rotatory chair test in addition to MRI and MR
      angiography. RESULTS: All patients presented with isolated vertigo and moderate
      to severe imbalance. The most common manifestation was unilateral nystagmus and
      falling in the opposite direction, which mimicked peripheral vestibulopathy. Six
      patients had unilateral lesion, and 2 showed bilateral lesions. The direction of
      the spontaneous nystagmus was all ipsilesional in the unilateral lesion. However,
      head impulse and bithermal caloric tests were normal. Other findings include
      periodic alternating nystagmus, perverted head shaking nystagmus, paroxysmal
      positional nystagmus, and impaired tilt suppression of the postrotatory
      nystagmus. Hypoplasia of the ipsilesional vertebral artery was the only abnormal
      finding on MR angiography in 3 patients. The prognosis was excellent.
      CONCLUSIONS: Isolated nodular infarction mostly presents with isolated vertigo
      mimicking acute peripheral vestibulopathy. However, severe imbalance and a
      negative head impulse test are important clinical discriminants between nodular
      infarcts and peripheral vestibular dysfunction. The findings of isolated nodular
      infarctions are consistent with impaired gravito-inertial processing of the
      vestibular signals and disrupted nodular inhibition on the vestibular secondary
      neurons and the velocity storage mechanism.

PMID- 19109546
TI  - Association between gait asymmetry and brain lesion location in stroke patients.
AB  - BACKGROUND AND PURPOSE: Associations between the site of brain injury and
      poststroke gait impairment are poorly understood. Temporal gait asymmetry after
      stroke is a salient index of gait dysfunction that has important functional
      consequences. The current study investigated whether subtraction lesion analysis
      could distinguish brain regions associated with persisting temporal gait
      asymmetry in chronic stroke patients. METHODS: Analysis was conducted on 37
      chronic ambulatory stroke patients (17 symmetrical gait, 20 asymmetrical gait).
      Spatiotemporal gait parameters were recorded using an instrumented walking
      surface. Lesions were traced from 3D T1-MRI, and region of interest images were
      generated. The lesion overlay of patients with symmetrical gait was subtracted
      from patients with asymmetrical gait to highlight voxels more frequently lesioned
      in asymmetrical patients and relatively spared in symmetrical patients. RESULTS:
      Demographic data were comparable between the 2 groups. Asymmetrical patients
      exhibited significantly higher National Institute of Health Stroke Scale neglect
      scores and more severe motor impairment. Gait asymmetry was significantly
      correlated to Chedoke-McMaster Stroke Scale leg (r=-0.767, P<0.001) and foot (r=
      0.759, P<0.001) scores, whereas gait speed correlated less strongly. After
      subtraction analysis, injury to the posterolateral putamen was evident 60% to 80%
      more frequently in the asymmetrical group compared to the symmetrical group.
      CONCLUSIONS: In this sample of ambulatory chronic stroke patients, damage to the
      posterolateral putamen was associated with temporal gait asymmetry. Further
      advances in our understanding of the neural correlates of gait asymmetry may
      provide prognostic markers for future persistent gait dysfunction and lead to
      early targeted rehabilitation when key regions are damaged.

PMID- 19109547
TI  - Optimal Tmax threshold for predicting penumbral tissue in acute stroke.
AB  - BACKGROUND AND PURPOSE: We sought to assess whether the volume of the ischemic
      penumbra can be estimated more accurately by altering the threshold selected for
      defining perfusion-weighting imaging (PWI) lesions. METHODS: DEFUSE is a
      multicenter study in which consecutive acute stroke patients were treated with
      intravenous tissue-type plasminogen activator 3 to 6 hours after stroke onset.
      Magnetic resonance imaging scans were obtained before, 3 to 6 hours after, and 30
      days after treatment. Baseline and posttreatment PWI volumes were defined
      according to increasing Tmax delay thresholds (>2, >4, >6, and >8 seconds).
      Penumbra salvage was defined as the difference between the baseline PWI lesion
      and the final infarct volume (30-day fluid-attenuated inversion recovery
      sequence). We hypothesized that the optimal PWI threshold would provide the
      strongest correlations between penumbra salvage volumes and various clinical and
      imaging-based outcomes. RESULTS: Thirty-three patients met the inclusion
      criteria. The correlation between infarct growth and penumbra salvage volume was
      significantly better for PWI lesions defined by Tmax >6 seconds versus Tmax >2
      seconds, as was the difference in median penumbra salvage volume in patients with
      a favorable versus an unfavorable clinical response. Among patients who did not
      experience early reperfusion, the Tmax >4 seconds threshold provided a more
      accurate prediction of final infarct volume than the >2 seconds threshold.
      CONCLUSIONS: Defining PWI lesions based on a stricter Tmax threshold than the
      standard >2 seconds delay appears to provide more a reliable estimate of the
      volume of the ischemic penumbra in stroke patients imaged between 3 and 6 hours
      after symptom onset. A threshold between 4 and 6 seconds appears optimal for
      early identification of critically hypoperfused tissue.

PMID- 19109548
TI  - Clinical prediction of functional outcome after ischemic stroke: the surprising
      importance of periventricular white matter disease and race.
AB  - BACKGROUND AND PURPOSE: We sought to build models that address questions of
      interest to patients and families by predicting short- and long-term mortality
      and functional outcome after ischemic stroke, while allowing for risk
      restratification as comorbid events accumulate. METHODS: A cohort of 451 ischemic
      stroke subjects in 1999 were interviewed during hospitalization, at 3 months, and
      at approximately 4 years. Medical records from the acute hospitalization were
      abstracted. All hospitalizations for 3 months poststroke were reviewed to
      ascertain medical and psychiatric comorbidities, which were categorized for
      analysis. Multivariable models were derived to predict mortality and functional
      outcome (modified Rankin Scale) at 3 months and 4 years. Comorbidities were
      included as modifiers of the 3-month models, and included in 4-year predictions.
      RESULTS: Poststroke medical and psychiatric comorbidities significantly increased
      short-term poststroke mortality and morbidity. Severe periventricular white
      matter disease (PVWMD) was significantly associated with poor functional outcome
      at 3 months, independent of other factors, such as diabetes and age; inclusion of
      this imaging variable eliminated other traditional risk factors often found in
      stroke outcomes models. Outcome at 3 months was a significant predictor of long
      term mortality and functional outcome. Black race was a predictor of 4-year
      mortality. CONCLUSIONS: We propose that predictive models for stroke outcome, as
      well as analysis of clinical trials, should include adjustment for comorbid
      conditions. The effects of PVWMD on short-term functional outcomes and black race
      on long-term mortality are findings that require confirmation.

PMID- 19109549
TI  - R2-recanalization of spontaneous carotid artery dissection.
AB  - BACKGROUND AND PURPOSE: We set out to investigate the predictors and time course
      for recanalization of spontaneous dissection of the cervical internal carotid
      artery (SICAD). METHODS: We prospectively included 249 consecutive patients (mean
      age, 45+/-11 years) with 268 SICAD. Ultrasound examinations were performed at
      presentation, during the first month, and then at 3, 6, and 12 months, and
      clinical follow-ups after 3, 6, and 12 months. RESULTS: Of 268 SICADs, 20 (7.5%)
      presented with <or=50% stenosis, 31 (11.6%) with 51% to 80% stenosis, 92 (34.3%)
      with 81% to 99% stenosis, and 125 (46.6%) with an occlusion. Antithrombotic
      treatment included anticoagulation in 174 (67%) patients, aspirin in 64 (24%)
      patients, and aspirin followed by anticoagulation or vice versa in 22 (8%)
      patients. Follow-up ultrasound showed normal findings in 160 (60%), <or=50%
      stenosis in 27 (10%), 51% to 80% stenosis in 4 (1%), 81% to 99% stenosis in 26
      (10%), and occlusion in 51 (19%) vessels. The rate of complete recanalization was
      16% at 1 month, 50% at 3 months, and 60% at 6 and 12 months. Initial occlusion of
      the dissected vessels reduced the odds of recanalization (OR, 4.0; 95% CI, 2.2
      7.3; P<0.001), whereas the occurrence of local symptoms and signs only at
      presentation were independently associated with complete recanalization (OR, 0.4;
      95% CI, 0.2-0.8; P=0.048). CONCLUSIONS: These results suggest that recanalization
      of SICAD occurs mainly within the first 6 months after the onset of symptoms.
      Initial occlusion reduces the likelihood of complete recanalization, whereas
      presentation with local symptoms and signs only increases it.

PMID- 19109550
TI  - Comparison of definitions of metabolic syndrome in relation to the risk of
      developing stroke and coronary heart disease in Finnish and Swedish cohorts.
AB  - BACKGROUND AND PURPOSE: The purpose of this study was to compare definitions of
      metabolic syndrome with regard to their prediction of stroke and coronary heart
      disease incidence. METHODS: The study comprises 4041 men and 3812 women of 6
      Finnish and Swedish cohorts aged 25 to 74 years at baseline. Hazard ratio was
      estimated applying Cox regression analyses adjusting for cohort, cholesterol, and
      smoking and using age as a time scale. A paired homogeneity test was performed to
      compare the differences. RESULTS: A total of 113 (47) ischemic and 43 (15)
      hemorrhagic stroke and 235 (50) coronary heart disease events were accumulated in
      men (women). Hazard ratios (95% CIs) for ischemic stroke in men were 1.59 (1.09
      to 2.32), 1.52 (1.01 to 2.28), 1.16 (0.77 to 1.74), and 1.27 (0.87 to 1.86),
      respectively, for the World Health Organization, National Cholesterol Education
      Program, National Cholesterol Education Program revised, and the International
      Diabetes Federation definitions of metabolic syndrome, and in women 2.20 (1.15 to
      4.19), 2.68 (1.47 to 4.87), 2.31 (1.27 to 4.20), and 1.91 (1.05 to 3.49),
      respectively. The corresponding hazard ratios (95% CIs) for coronary heart
      disease were 1.57 (1.21 to 2.04), 1.51 (1.15 to 1.99), 1.63 (1.25 to 2.13), and
      1.46 (1.12 to 1.89) in men and 1.32 (0.69 to 2.51), 1.54 (0.85 to 2.79), 1.81
      (1.02 to 3.21), and 2.47 (1.37 to 4.45) in women. None of the definitions of
      metabolic syndrome predicted hemorrhagic stroke. There was no difference between
      definitions of metabolic syndrome and between a full definition and its
      individual components. CONCLUSIONS: Metabolic syndrome as well as its individual
      components predicted the incidence of the ischemic stroke and the coronary heart
      disease equally well and should be treated equally as well.

PMID- 19109551
TI  - MRI biomarkers of vascular damage and atrophy predicting mortality in a memory
      clinic population.
AB  - BACKGROUND AND PURPOSE: MRI biomarkers play an important role in the diagnostic
      work-up of dementia, but their prognostic value is less well-understood. We
      investigated if simple MRI rating scales predict mortality in a memory clinic
      population. METHODS: We included 1138 consecutive patients attending our memory
      clinic. Diagnostic categories were: subjective complaints (n=220), mild cognitive
      impairment (n=160), Alzheimer disease (n=357), vascular dementia (n=46), other
      dementia (n=136), and other diagnosis (n=219). Baseline MRIs were assessed using
      visual rating scales for medial temporal lobe atrophy (range, 0-4), global
      cortical atrophy (range, 0-3), and white matter hyperintensities (range, 0-3).
      Number of microbleeds and presence of infarcts were recorded. Cox-regression
      models were used to calculate the risk of mortality. RESULTS: Mean follow-up
      duration was 2.6 (+/-1.9) years. In unadjusted models, all MRI markers except
      infarcts predicted mortality. After adjustment for age, sex, and diagnosis, white
      matter hyperintensities, and microbleeds predicted mortality (white matter
      hyperintensities: hazard ratio [HR], 1.2; 95% CI, 1.0-1.4; microbleeds: HR, 1.02
      95% CI, 1.00-1.03; categorized: HR, 1.5; 95% CI, 1.1-2.0). The predictive effect
      of global cortical atrophy was restricted to younger subjects (HR, 1.7; 95% CI,
      1.2-2.6). An interaction between microbleeds and global cortical atrophy
      indicated that mortality was especially high in patients with both microbleeds
      and global cortical atrophy. CONCLUSIONS: Simple MRI biomarkers, in addition to
      their diagnostic use, have a prognostic value with respect to mortality in a
      memory clinic population. Microbleeds were the strongest predictor of mortality.

PMID- 19109552
TI  - Apolipoprotein(a): a natural regulator of inflammation.

PMID- 19109553
TI  - Adipose-derived stem cells: characterization and current application in
      orthopaedic tissue repair.
AB  - Orthopaedic tissues, such as bone, cartilage, intervertebral disc and tendon,
      contain cells that are difficult to culture and stimulate in vitro for repair of
      damaged tissue. Stem cells have the ability to self-renew and differentiate into
      many tissue types. Recent progress in stem cell research has led to an
      enthusiastic effort to utilize stem cells for orthopaedic tissue regeneration.
      Due to ease of harvest and abundance, adipose-derived mesenchymal cells (ASC) are
      an attractive, readily available adult stem cell that has become increasingly
      popular for use in many stem cell applications. Recent progress has been made in
      characterizing ASC and looking mechanistically at gene expression and cellular
      pathways involved in differentiation. This review focuses on (i) the
      characterization of ASC through expression of appropriate surface markers; (ii)
      modulation of in vitro differentiation of ASC through different scaffolds, growth
      factors, and media; and (iii) the use of ASC in orthopaedic tissue repair.
      Strategies for repair involve the use of differentiated or undifferentiated,
      fresh or passaged ASC, in conjunction with appropriate choice of media, growth
      factors and scaffolds. Recent in vivo studies utilizing ASC are discussed giving
      results on defect repair and potential for clinical orthopaedic tissue
      regeneration.

PMID- 19109554
TI  - Pyrin and ASC co-localize to cellular sites that are rich in polymerizing actin.
AB  - Familial Mediterranean fever (FMF) is an autoinflammatory disease caused by
      mutations in the MEFV locus, which encodes the protein pyrin. While it is known
      that pyrin is expressed in myeloid cells and several fibroblastic cell types, the
      exact function of pyrin in these cells and the mechanism underlying the
      pathological effect of pyrin mutations have yet to be revealed. Here, we document
      that in migrating human monocytes, pyrin protein is dramatically polarized at the
      leading edge, where it co-localizes with polymerizing actin. ASC (Apoptosis
      associated Speck protein with CARD domain), a known pyrin-interacting protein and
      a critical component of the inflamma-some, is also located at the leading edge in
      migrating monocytes. Similarly, both pyrin and ASC concentrate in dynamically
      polymerizing actin-rich tails generated by Listeria monocytogenes. Pyrin's B-box
      and coiled-coil region is required for its association with Listeria tails. Pyrin
      also binds, with low affinity and via the same domains, to actin, VASP, and Arp3.
      Though disease-causing mutations in pyrin do not appear to alter its localization
      to the leading edge or to Listeria rocket tails, they could potentially have
      important functional consequences in the context of processes such as migration
      and cell synapse formation. The co-localization of pyrin and ASC together at such
      sites may provide an important link between cytoskeletal signaling and
      inflammasome function.

PMID- 19109555
TI  - ATR-dependent phosphorylation of FANCA on serine 1449 after DNA damage is
      important for FA pathway function.
AB  - Previous work has shown several proteins defective in Fanconi anemia (FA) are
      phosphorylated in a functionally critical manner. FANCA is phosphorylated after
      DNA damage and localized to chromatin, but the site and significance of this
      phosphorylation are unknown. Mass spectrometry of FANCA revealed one
      phosphopeptide, phosphorylated on serine 1449. Serine 1449 phosphorylation was
      induced after DNA damage but not during S phase, in contrast to other
      posttranslational modifications of FA proteins. Furthermore, the S1449A mutant
      failed to completely correct a variety of FA-associated phenotypes. The DNA
      damage response is coordinated by phosphorylation events initiated by apical
      kinases ATM (ataxia telangectasia mutated) and ATR (ATM and Rad3-related), and
      ATR is essential for proper FA pathway function. Serine 1449 is in a consensus
      ATM/ATR site, phosphorylation in vivo is dependent on ATR, and ATR phosphorylated
      FANCA on serine 1449 in vitro. Phosphorylation of FANCA on serine 1449 is a DNA
      damage-specific event that is downstream of ATR and is functionally important in
      the FA pathway.

PMID- 19109556
TI  - Chaperoning erythropoiesis.
AB  - Multisubunit complexes containing molecular chaperones regulate protein
      production, stability, and degradation in virtually every cell type. We are
      beginning to recognize how generalized and tissue-specific chaperones regulate
      specialized aspects of erythropoiesis. For example, chaperones intersect with
      erythropoietin signaling pathways to protect erythroid precursors against
      apoptosis. Molecular chaperones also participate in hemoglobin synthesis, both
      directly and indirectly. Current knowledge in these areas only scratches the
      surface of what is to be learned. Improved understanding of how molecular
      chaperones regulate erythropoietic development and hemoglobin homeostasis should
      identify biochemical pathways amenable to pharmacologic manipulation in a variety
      of red blood cell disorders including thalassemia and other anemias associated
      with hemoglobin instability.

PMID- 19109557
TI  - Active oral regimen for elderly adults with newly diagnosed acute myelogenous
      leukemia: a preclinical and phase 1 trial of the farnesyltransferase inhibitor
      tipifarnib (R115777, Zarnestra) combined with etoposide.
AB  - The farnesyltransferase inhibitor tipifarnib exhibits modest activity against
      acute myelogenous leukemia. To build on these results, we examined the effect of
      combining tipifarnib with other agents. Tipifarnib inhibited signaling downstream
      of the farnesylated small G protein Rheb and synergistically enhanced etoposide
      induced antiproliferative effects in lymphohematopoietic cell lines and acute
      myelogenous leukemia isolates. We subsequently conducted a phase 1 trial of
      tipifarnib plus etoposide in adults over 70 years of age who were not candidates
      for conventional therapy. A total of 84 patients (median age, 77 years) received
      224 cycles of oral tipifarnib (300-600 mg twice daily for 14 or 21 days) plus
      oral etoposide (100-200 mg daily on days 1-3 and 8-10). Dose-limiting toxicities
      occurred with 21-day tipifarnib. Complete remissions were achieved in 16 of 54
      (30%) receiving 14-day tipifarnib versus 5 of 30 (17%) receiving 21-day
      tipifarnib. Complete remissions occurred in 50% of two 14-day tipifarnib cohorts:
      3A (tipifarnib 600, etoposide 100) and 8A (tipifarnib 400, etoposide 200). In
      vivo, tipifarnib plus etoposide decreased ribosomal S6 protein phosphorylation
      and increased histone H2AX phosphorylation and apoptosis. Tipifarnib plus
      etoposide is a promising orally bioavailable regimen that warrants further
      evaluation in elderly adults who are not candidates for conventional induction
      chemotherapy. These clinical studies are registered at www.clinicaltrials.gov as
      #NCT00112853.

PMID- 19109559
TI  - The impact of Fc engineering on an anti-CD19 antibody: increased Fcgamma receptor
      affinity enhances B-cell clearing in nonhuman primates.
AB  - CD19, a B cell-restricted receptor critical for B-cell development, is expressed
      in most B-cell malignancies. The Fc-engineered anti-CD19 antibody, XmAb5574, has
      enhanced Fcgamma receptor (FcgammaR) binding affinity, leading to improved
      FcgammaR-dependent effector cell functions and antitumor activity in murine
      xenografts compared with the non-Fc-engineered anti-CD19 IgG1 analog. Here, we
      use XmAb5574 and anti-CD19 IgG1 to further dissect effector cell functions in an
      immune system closely homologous to that of humans, the cynomolgus monkey.
      XmAb5574 infusion caused an immediate and dose-related B-cell depletion in the
      blood (to <10% of baseline levels) concomitant with a sustained reduction of
      natural killer (NK) cells. NK cells had fully recovered by day 15, whereas B-cell
      recovery was underway by day 57. B cells in secondary lymphoid tissues were
      depleted (to 34%-61% of vehicle), with involuted germinal centers apparent in the
      spleen. Anti-CD19 IgG1 had comparable serum exposure to XmAb5574 but demonstrated
      no B-cell depletion and no sustained NK-cell reduction. Thus, increasing FcgammaR
      binding affinity dramatically increased B-cell clearing. We propose that effector
      cell functions, possibly those involving NK cells, mediate XmAb5574 potency in
      cynomolgus monkeys, and that enhancing these mechanisms should advance the
      treatment of B-cell malignancies in humans.

PMID- 19109558
TI  - Sphingosine kinase regulates the rate of endothelial progenitor cell
      differentiation.
AB  - Circulating endothelial progenitor cells (EPCs) are incorporated into foci of
      neovascularization where they undergo differentiation to mature endothelial cells
      (ECs). We show here that the enzyme sphingosine kinase-1 (SK-1) regulates the
      rate and direction of EPC differentiation without effect on the hematopoietic
      compartment. EPCs have high levels of SK-1 activity, which diminishes with
      differentiation and is, at least partially, responsible for maintaining their EPC
      phenotype. EPCs from SK-1 knockout mice form more adherent EC units and acquire a
      mature EC phenotype more rapidly. Conversely, EPCs from mice overexpressing SK-1
      in the EC compartment are retarded in their differentiation. Exogenous regulation
      of SK-1 levels in normal EPCs, by genetic and pharmacologic means, including the
      immunomodulating drug FTY720, recapitulates these effects on EC differentiation.
      SK-1 knockout mice have higher levels of circulating EPCs, an exaggerated
      response to erythropoietin-induced EPC mobilization, and, in a mouse model of
      kidney ischemia reperfusion injury, exhibit a recovery similar to that of
      ischemic mice administered exogenous EPCs. Thus, SK-1 is a critical player in EPC
      differentiation into EC pointing to the potential utility of SK-1 modifying
      agents in the specific manipulation of endothelial development and repair.

PMID- 19109560
TI  - A randomized controlled trial comparing standard- and low-dose strategies for
      transfusion of platelets (SToP) to patients with thrombocytopenia.
AB  - A noninferiority study was performed comparing low-dose and standard-dose
      prophylactic platelet transfusions. A double-blind randomized controlled trial
      (RCT) was performed in 6 sites in 3 countries. Thrombocytopenic adults requiring
      prophylactic platelet transfusion were randomly allocated to standard-dose (300
      600 x 10(9) platelets/product) or low-dose (150- < 300 x 10(9) platelets/product)
      platelets. The primary outcome (World Health Organization [WHO] bleeding > or =
      grade 2) was assessed daily through clinical examination, patient interview, and
      chart review. A WHO grade was assigned through adjudication. The Data Safety
      Monitoring Board stopped the study because the difference in the grade 4 bleeding
      reached the prespecified threshold of 5%. At this time, 129 patients had been
      randomized and 119 patients were included in the analysis (58 low dose; 61
      standard dose). Three patients in the low-dose arm (5.2%) had grade 4 bleeds
      compared with none in the standard-dose arm. WHO bleeding grade 2 or higher was
      49.2% (30/61) in the standard-dose arm and 51.7% (30/58) in the low-dose group
      (relative risk [RR], 1.052; 95% confidence interval [CI], 0.737-1.502). A higher
      rate of grade 4 bleeding in patients receiving low-dose prophylactic platelet
      transfusions resulted in this RCT being stopped. Whether this finding was due to
      chance or represents a real difference requires further investigation. These
      clinical studies are registered on (http://www.clinicaltrials.gov) as
      NCT00420914.

PMID- 19109561
TI  - Hematopoietic defects in the Ts1Cje mouse model of Down syndrome.
AB  - Down syndrome (DS) persons are born with various hematopoietic abnormalities,
      ranging from relatively benign, such as neutrophilia and macrocytosis, to a more
      severe transient myeloproliferative disorder (TMD). In most cases, these
      abnormalities resolve in the first few months to years of life. However,
      sometimes the TMD represents a premalignant disease that develops into acute
      megakaryocytic leukemia (AMKL), usually in association with acquired GATA1
      mutations. To gain insight into the mechanisms responsible for these
      abnormalities, we analyzed the hematopoietic development of the Ts1Cje mouse
      model of DS. Our analyses identified defects in mature blood cells, including
      macrocytosis and anemia, as well as abnormalities in fetal liver and bone marrow
      stem and progenitor cell function. Despite these defects, the Ts1Cje mice do not
      develop disease resembling either TMD or AMKL, and this was not altered by a loss
      of function allele of Gata1. Thus, loss of Gata1 and partial trisomy of
      chromosome 21 orthologs, when combined, do not appear to be sufficient to induce
      TMD or AMKL-like phenotypes in mice.

PMID- 19109562
TI  - The distal carboxyl-terminal domains of ADAMTS13 are required for regulation of
      in vivo thrombus formation.
AB  - ADAMTS13 is a multidomain protease that limits platelet thrombogenesis through
      the cleavage of von Willebrand factor (VWF). We previously identified 2 types of
      mouse Adamts13 gene: the 129/Sv-strain Adamts13 gene encodes the long-form
      ADAMTS13 having the same domains as human ADAMTS13, whereas the C57BL/6-strain
      Adamts13 gene encodes the short-form ADAMTS13 lacking the distal C-terminal
      domains. To assess the physiologic significance of the distal C-terminal domains
      of ADAMTS13, we generated and analyzed 129/Sv-genetic background congenic mice
      (Adamts13(S/S)) that carry the short-form ADAMTS13. Similar to wild-type 129/Sv
      mice (Adamts13(L/L)), Adamts13(S/S) did not have ultralarge VWF multimers in
      plasma, in contrast to 129/Sv-genetic background ADAMTS13-deficient mice
      (Adamts13(-/-)). However, in vitro thrombogenesis under flow at a shear rate of
      5000 s(-1) was accelerated in Adamts13(S/S) compared with Adamts13(L/L). Both in
      vivo thrombus formation in ferric chloride-injured arterioles and
      thrombocytopenia induced by collagen plus epinephrine challenge were more
      dramatic in Adamts13(S/S) than in Adamts13(L/L) but less than in Adamts13(-/-).
      These results suggested that the C-terminally truncated ADAMTS13 exhibited
      decreased activity in the cleavage of VWF under high shear rate. Role of the C
      terminal domains may become increasingly important under prothrombotic
      conditions.

PMID- 19109563
TI  - A role for MEIS1 in MLL-fusion gene leukemia.
AB  - Leukemias with MLL rearrangements are characterized by high expression of the
      homeobox gene MEIS1. In these studies, we knocked down Meis1 expression by shRNA
      lentivirus transduction in murine Mll-AF9 leukemia cells. Meis1 knockdown
      resulted in decreased proliferation and survival of murine Mll-AF9 leukemia
      cells. We also observed reduced clonogenic capacity and increased monocytic
      differentiation. The establishment of leukemia in transplantation recipients was
      significantly delayed by Meis1 knockdown. Gene expression profiling of cells
      transduced with Meis1 shRNA showed reduced expression of genes associated with
      cell cycle entry and progression. shRNA-mediated knockdown of MEIS1 in human MLL
      fusion gene leukemia cell lines resulted in reduced cell growth. These results
      show that MEIS1 expression is important for MLL-rearranged leukemias and suggest
      that MEIS1 promotes cell-cycle entry. Targeting MEIS1 may have therapeutic
      potential for treating leukemias expressing this transcription factor.

PMID- 19109564
TI  - Functional genomics in zebrafish permits rapid characterization of novel platelet
      membrane proteins.
AB  - In this study, we demonstrate the suitability of the vertebrate Danio rerio
      (zebrafish) for functional screening of novel platelet genes in vivo by reverse
      genetics. Comparative transcript analysis of platelets and their precursor cell,
      the megakaryocyte, together with nucleated blood cell elements, endothelial
      cells, and erythroblasts, identified novel platelet membrane proteins with
      hitherto unknown roles in thrombus formation. We determined the phenotype induced
      by antisense morpholino oligonucleotide (MO)-based knockdown of 5 of these genes
      in a laser-induced arterial thrombosis model. To validate the model, the genes
      for platelet glycoprotein (GP) IIb and the coagulation protein factor VIII were
      targeted. MO-injected fish showed normal thrombus initiation but severely
      impaired thrombus growth, consistent with the mouse knockout phenotypes, and
      concomitant knockdown of both resulted in spontaneous bleeding. Knockdown of 4 of
      the 5 novel platelet proteins altered arterial thrombosis, as demonstrated by
      modified kinetics of thrombus initiation and/or development. We identified a
      putative role for BAMBI and LRRC32 in promotion and DCBLD2 and ESAM in inhibition
      of thrombus formation. We conclude that phenotypic analysis of MO-injected
      zebrafish is a fast and powerful method for initial screening of novel platelet
      proteins for function in thrombosis.

PMID- 19109565
TI  - Genetic deletion of JAM-C reveals a role in myeloid progenitor generation.
AB  - Hematopoietic stem cells (HSCs) have the capacity to self-renew and continuously
      differentiate into all blood cell lineages throughout life. At each branching
      point during differentiation, interactions with the environment are key in the
      generation of daughter cells with distinct fates. Here, we examined the role of
      the cell adhesion molecule JAM-C, a protein known to mediate cellular polarity
      during spermatogenesis, in hematopoiesis. We show that murine JAM-C is highly
      expressed on HSCs in the bone marrow (BM). Expression correlates with self
      renewal, the highest being on long-term repopulating HSCs, and decreases with
      differentiation, which is maintained longest among myeloid committed progenitors.
      Inclusion of JAM-C as a sole marker on lineage-negative BM cells yields HSC
      enrichments and long-term multilineage reconstitution when transferred to
      lethally irradiated mice. Analysis of Jam-C-deficient mice showed that two-thirds
      die within 48 hours after birth. In the surviving animals, loss of Jam-C leads to
      an increase in myeloid progenitors and granulocytes in the BM. Stem cells and
      myeloid cells from fetal liver are normal in number and homing to the BM. These
      results provide evidence that JAM-C defines HSCs in the BM and that JAM-C plays a
      role in controlling myeloid progenitor generation in the BM.

PMID- 19109568
TI  - Three-dimensional electron microscopy of individual nanoparticles.
AB  - The characterization of nanomaterials with complex three-dimensional (3D)
      geometries is required to further research and enable the continuing development
      of nanotechnology. In this manuscript, we report a protocol which combines
      focused ion beam (FIB) milling, thin film deposition and solution chemistry to
      optimize a rotation holder for 3D structural and chemical analysis of
      nanoparticles. This protocol is used to customize the geometry, surface and
      chemistry of a scanning transmission electron microscope (STEM) or transmission
      electron microscope (TEM) rotation holder for the nanoparticle system of
      interest. To illustrate this concept, rotation holder stubs were optimized to
      facilitate the 3D STEM imaging and analysis of core-shell nanoparticles used for
      DNA detection. Using this approach, it was possible to characterize the
      morphology, optoelectronic properties and chemical composition of individual core
      shell nanoparticles in 3D. STEM images were captured at regular angular intervals
      over a complete 360 degrees rotation to eliminate missing wedge artifacts.
      Electron energy-loss spectroscopy (EELS) spectrum images were acquired
      intermittently for comparative chemical analysis. This approach allows the 3D
      STEM/TEM analysis to be performed with the nanoparticle of interest cantilevered
      over vacuum to minimize substrate effects. Standard tomography techniques were
      used to reconstruct the 3D structure of the individual nanoparticles from the
      STEM HAADF rotation series. EELS spectrum imaging was used to determine the local
      material properties such as composition, band-gap and plasmon energy. The
      nanoparticle analysis protocol reported here can easily be adapted to facilitate
      3D TEM/STEM analysis of other nanomaterial systems.

PMID- 19109566
TI  - Population-specific genetic variants important in susceptibility to cytarabine
      arabinoside cytotoxicity.
AB  - Cytarabine arabinoside (ara-C) is an antimetabolite used to treat hematologic
      malignancies. Resistance is a common reason for treatment failure with adverse
      side effects contributing to morbidity and mortality. Identification of genetic
      factors important in susceptibility to ara-C cytotoxicity may allow for
      individualization of treatment. We used an unbiased whole-genome approach using
      lymphoblastoid cell lines derived from persons of European (CEU) or African (YRI)
      ancestry to identify these genetic factors. We interrogated more than 2 million
      single nucleotide polymorphisms (SNPs) for association with susceptibility to ara
      C and narrowed our focus by concentrating on SNPs that affected gene expression.
      We identified a unique pharmacogenetic signature consisting of 4 SNPs explaining
      51% of the variability in sensitivity to ara-C among the CEU and 5 SNPs
      explaining 58% of the variation among the YRI. Population-specific signatures
      were secondary to either (1) polymorphic SNPs in one population but monomorphic
      in the other, or (2) significant associations of SNPs with cytotoxicity or gene
      expression in one population but not the other. We validated the gene expression
      cytotoxicity relationship for a subset of genes in a separate group of
      lymphoblastoid cell lines. These unique genetic signatures comprise novel genes
      that can now be studied further in functional studies.

PMID- 19109569
TI  - Videos in clinical medicine. Basic splinting techniques.

PMID- 19109570
TI  - Images in clinical medicine. Occult hip fracture.

PMID- 19109567
TI  - B7-H4-deficient mice display augmented neutrophil-mediated innate immunity.
AB  - B7-H4 is an immunoglobulin superfamily molecule and shown to be inhibitory for T
      cell responses. To explore physiologic roles of B7-H4, we created B7-H4-deficient
      (KO) mice by genetic targeting. B7-H4KO mice are healthy and their T- and B-cell
      responses to polyclonal antigens are in normal range. However, B7-H4KO mice are
      more resistant to infection by Listeria monocytogenes than their littermates.
      Within 3 days after infection, bacterial colonies in livers and spleens are
      significantly lower than the controls, suggesting a role of B7-H4 in enhancing
      innate immunity. Further studies demonstrate that neutrophils increase in
      peripheral organs of B7-H4KO mice more so than their littermates but their
      bactericidal functions remain unchanged. Augmented innate resistance is
      completely dependent on neutrophils, even in the absence of adaptive immunity. In
      vitro B7-H4 inhibits the growth of bone marrow-derived neutrophil progenitors,
      suggesting an inhibitory function of B7-H4 in neutrophil expansion. Our results
      identify B7-H4 as a negative regulator of the neutrophil response to infection
      and provide a new target for manipulation of innate immunity.

PMID- 19109571
TI  - Melamine and the global implications of food contamination.

PMID- 19109572
TI  - Culture shock--patient as icon, icon as patient.

PMID- 19109573
TI  - Inhibition of the Bcl-xL deamidation pathway in myeloproliferative disorders.
AB  - BACKGROUND: The myeloproliferative disorders are clonal disorders with frequent
      somatic gain-of-function alterations affecting tyrosine kinases. In these
      diseases, there is an increase in DNA damage and a risk of progression to acute
      leukemia. The molecular mechanisms in myeloproliferative disorders that prevent
      apoptosis induced by damaged DNA are obscure. METHODS: We searched for
      abnormalities of the proapoptotic Bcl-x(L) deamidation pathway in primary cells
      from patients with chronic myeloid leukemia (CML) or polycythemia vera,
      myeloproliferative disorders associated with the BCR-ABL fusion kinase and the
      Janus tyrosine kinase 2 (JAK2) V617F mutation, respectively. RESULTS: The Bcl
      x(L) deamidation pathway was inhibited in myeloid cells, but not T cells, in
      patients with CML or polycythemia vera. DNA damage did not increase levels of the
      amiloride-sensitive sodium-hydrogen exchanger isoform 1 (NHE-1), intracellular
      pH, Bcl-x(L) deamidation, and apoptosis. Inhibition of the pathway was reversed
      by enforced alkalinization or overexpression of NHE-1, leading to a restoration
      of apoptosis. In patients with CML, the pathway was blocked in CD34+ progenitor
      cells and mature myeloid cells. Imatinib or JAK2 inhibitors reversed inhibition
      of the pathway in cells from patients with CML and polycythemia vera,
      respectively, but not in cells from a patient with resistance to imatinib because
      of a mutation in the BCR-ABL kinase domain. CONCLUSIONS: BCR-ABL and mutant JAK2
      inhibit the Bcl-x(L) deamidation pathway and the apoptotic response to DNA damage
      in primary cells from patients with CML or polycythemia vera.

PMID- 19109575
TI  - Clinical practice. Acute pulmonary embolism.

PMID- 19109577
TI  - Images in clinical medicine. Hypogonadism due to pituicytoma in an identical
      twin.

PMID- 19109576
TI  - Molecular basis of metastasis.

PMID- 19109574
TI  - Azathioprine or methotrexate maintenance for ANCA-associated vasculitis.
AB  - BACKGROUND: Current standard therapy for Wegener's granulomatosis and microscopic
      polyangiitis combines corticosteroids and cyclophosphamide to induce remission,
      followed by a less toxic immunosuppressant such as azathioprine or methotrexate
      for maintenance therapy. However, azathioprine and methotrexate have not been
      compared with regard to safety and efficacy. METHODS: In this prospective, open
      label, multicenter trial, we randomly assigned patients with Wegener's
      granulomatosis or microscopic polyangiitis who entered remission with intravenous
      cyclophosphamide and corticosteroids to receive oral azathioprine (at a dose of
      2.0 mg per kilogram of body weight per day) or methotrexate (at a dose of 0.3 mg
      per kilogram per week, progressively increased to 25 mg per week) for 12 months.
      The primary end point was an adverse event requiring discontinuation of the study
      drug or causing death; the sample size was calculated on the basis of the primary
      hypothesis that methotrexate would be less toxic than azathioprine. The secondary
      end points were severe adverse events and relapse. RESULTS: Among 159 eligible
      patients, 126 (79%) had a remission, were randomly assigned to receive a study
      drug in two groups of 63 patients each, and were followed for a mean (+/-SD)
      period of 29+/-13 months. Adverse events occurred in 29 azathioprine recipients
      and 35 methotrexate recipients (P=0.29); grade 3 or 4 events occurred in 5
      patients in the azathioprine group and 11 patients in the methotrexate group
      (P=0.11). The primary end point was reached in 7 patients who received
      azathioprine as compared with 12 patients who received methotrexate (P=0.21),
      with a corresponding hazard ratio for methotrexate of 1.65 (95% confidence
      interval, 0.65 to 4.18; P=0.29). There was one death in the methotrexate group.
      Twenty-three patients who received azathioprine and 21 patients who received
      methotrexate had a relapse (P=0.71); 73% of these patients had a relapse after
      discontinuation of the study drug. CONCLUSIONS: These results do not support the
      primary hypothesis that methotrexate is safer than azathioprine. The two agents
      appear to be similar alternatives for maintenance therapy in patients with
      Wegener's granulomatosis and microscopic polyangiitis after initial remission.
      (ClinicalTrials.gov number, NCT00349674.)

PMID- 19109578
TI  - Case records of the Massachusetts General Hospital. Case 40-2008. A 26-year-old
      man with blurred vision.

PMID- 19109579
TI  - Pediatric anxiety--underrecognized and undertreated.

PMID- 19109580
TI  - Thrombolysis 3 to 4.5 hours after acute ischemic stroke.

PMID- 19109581
TI  - Accuracy of CT colonography for colorectal cancer screening.

PMID- 19109582
TI  - Gonadotropin-releasing hormone agonists for endometriosis.

PMID- 19109583
TI  - Medical mystery: A 71-year-old man with pancytopenia--the answer.

PMID- 19109584
TI  - More on propranolol for hemangiomas of infancy.

PMID- 19109585
TI  - Cardiac amyloidosis with the E526V mutation of the fibrinogen A alpha-chain.

PMID- 19109586
TI  - Concordance for islet autoimmunity among monozygotic twins.

PMID- 19109587
TI  - Substitution of connexin40 with connexin45 prevents hyperreninemia and attenuates
      hypertension.
AB  - Connexins (Cxs) are a family of transmembrane proteins that form gap junctions
      with unique and redundant biophysical functions. Juxtaglomerular cells express
      Cx40, which is crucial to the control of renin secretion by blood pressure and
      angiotensin II, and mice that lack Cx40 have high plasma renin and hypertension.
      To examine whether normal juxtaglomerular cell function depends on the unique
      properties of Cx40, we measured renin release in mice where the coding sequence
      for Cx40 was replaced by that for Cx45, using the knock-in method. We first found
      that the knock-in strategy indeed resulted in expression of Cx45 but not Cx40 in
      the juxtaglomerular cells of these mice. The plasma renin concentration of the
      knock-in mice was similar to that in wild-type mice. The high blood pressure of
      the Cx40 knockout mice was significantly reduced when Cx45 was knocked into the
      locus but remained mildly elevated compared to wild-type mice. Blockade of
      angiotensin II formation by enalapril increased the plasma renin concentration in
      wild-type and the Cx45 knock-in mice but not in the Cx40 knockout mice. Infusion
      of angiotensin II into isolated perfused kidneys results in decreased renin
      release, a phenomenon that was attenuated in the Cx40 knockout mice. However, in
      the Cx45 knock-in mice, angiotensin II suppressed renin release similar to its
      effect in wild type mice. Unilateral renal artery stenosis increased the plasma
      renin concentration and blood pressure in both the wild-type and the Cx45 knock
      in mice but not in the Cx40 knockout mice. Since Cx40 can be replaced by Cx45, a
      connexin with a significantly lower conductivity, we suggest that the regulation
      of renin release is not dependent on the unique electrical properties of these
      channel proteins.

PMID- 19109588
TI  - Nocturnal hemodialysis does not improve overall measures of quality of life
      compared to conventional hemodialysis.
AB  - We conducted a randomized controlled trial to compare the quality of life of 52
      patients undergoing nocturnal hemodialysis and conventional hemodialysis. Quality
      of life was measured using a number of established methods including the Kidney
      Disease Quality of Life Short Form and the preference-based Euroqol EQ-5D
      questionnaire (whose scores varied from 0 to 1). The primary outcome was a change
      in the Euroqol EQ-5D index scores between baseline and 6 months. We performed
      additional analyses comparing change in quality of life from pre-randomization
      (when patients were unaware of treatment allocation) to 6 months. Other analyses
      considered the impact of nocturnal hemodialysis on four pre-selected Kidney
      Disease Quality of Life Short Form domains, and the longer term impact of
      nocturnal hemodialysis on quality of life. Compared with conventional
      hemodialysis, nocturnal hemodialysis increased Euroqol-EQ-5D index scores by
      0.05, which was not significantly different from baseline. When six-month values
      were compared with pre-randomization values rather than baseline values, the
      between group difference was larger (0.12) though it was still not statistically
      significant (P=.06). Nocturnal hemodialysis was associated with clinically and
      statistically significant improvements in selected kidney-specific quality of
      life domains (P=.01 for effects of kidney disease; P=.02 for burden of kidney
      disease). Our primary quality of life analysis did not demonstrate a
      statistically significant change between nocturnal hemodialysis and conventional
      hemodialysis, though statistically significant and clinically important changes
      in some secondary kidney-disease- specific measures were observed.

PMID- 19109589
TI  - Phase 0 clinical studies in oncology.

PMID- 19109590
TI  - An agonist-antagonist interaction model for prolactin release following
      risperidone and paliperidone treatment.
AB  - A mechanistic pharmacokinetic/pharmacodynamic model is presented, characterizing
      the time course of prolactin in healthy as well as schizophrenic subjects
      following the administration of various doses and formulations of the
      antipsychotic drugs risperidone and paliperidone. Prolactin concentrations from
      nine studies (1,462 subjects) were analyzed in NONMEM. A competitive agonist
      antagonist interaction model described the competition between these drugs and
      dopamine for the D(2) receptors that regulate prolactin release. Tolerance
      development was explained by a feedback loop with prolactin stimulating dopamine
      release, whereas models wherein tolerance is described in terms of depletion of a
      prolactin pool did not explain the data well. The diurnal prolactin rhythm was
      described by a two-period cosine function. Baseline prolactin was health-status
      dependent and higher in women than in men, although the drug-induced release was
      less than proportional to baseline. This quantitative mechanism-based model is
      the first to describe prolactin release in patients, and it confirms that
      paliperidone and risperidone have similar potencies for prolactin release.

PMID- 19109591
TI  - Novel clinical trial designs for innovative therapies.

PMID- 19109593
TI  - Declining public health burden of digoxin toxicity: decreased use or safer
      prescribing?

PMID- 19109595
TI  - Sialic acid dependence in rotavirus host cell invasion.
AB  - We used NMR spectroscopy, molecular modeling and infectivity competition assays
      to investigate the key interactions between the spike protein (VP8(*)) from
      'sialidase-insensitive' human Wa and 'sialidase-sensitive' porcine CRW-8
      rotaviruses and the glycans of gangliosides G(M1) and G(D1a). Our data provide
      strong evidence that N-acetylneuraminic acid is a key determinant for binding of
      these rotaviruses. This is in contrast to the widely accepted paradigm that
      sialic acids are irrelevant in host cell recognition by sialidase-insensitive
      rotaviruses.

PMID- 19109594
TI  - Cytochrome bd confers nitric oxide resistance to Escherichia coli.
AB  - The aerobic respiratory chain of Escherichia coli has two terminal quinol
      oxidases: cytochrome bo and cytochrome bd. Cytochrome bd was thought to function
      solely to facilitate micro-aerobic respiration. However, it has recently been
      shown to be overexpressed under conditions of nitric oxide (NO) stress; we show
      here that cytochrome bd is crucial for protecting E. coli cells from NO-induced
      growth inhibition by virtue of its fast NO dissociation rate.

PMID- 19109596
TI  - Linear-quadratic-Gaussian control for adaptive optics systems using a hybrid
      model.
AB  - This paper presents a linear-quadratic-Gaussian (LQG) design based on the
      equivalent discrete-time model of an adaptive optics (AO) system. The design
      model incorporates deformable mirror dynamics, an asynchronous wavefront sensor
      and zero-order hold operation, and a continuous-time model of the incident
      wavefront. Using the structure of the discrete-time model, the dimensions of the
      Riccati equations to be solved are reduced. The LQG controller is shown to
      improve AO system performance under several conditions.

PMID- 19109597
TI  - Error analysis and compensation method of focus detection in exposure apparatus.
AB  - An original approach to measurement accuracy of a typical focus sensor in
      conventional integrated circuit lithographic equipment is introduced. Causes of
      measurement error in the focus sensor are theoretically analyzed and found to be
      generated mainly from interactions between imperfections of the optical system
      and the actual surface of processed wafers. We derive mathematical formulations
      describing these errors, which are confirmed by the experimental results
      performed by using an optical setup composed of the focus sensor and samples on
      which the wafer surface condition is reproduced. Furthermore, several novel
      techniques that are intended to reduce those measurement errors are successfully
      demonstrated.

PMID- 19109598
TI  - Modal-based tomographic imaging from far-zone observations.
AB  - A novel method of optical diffraction tomography (ODT) to image weakly
      scattering, electrically large, two-dimensional (2D) objects using the far-zone
      scattered field data is presented. The proposed technique is based on the
      expansion of the target object function in terms of Fourier-Bessel basis
      functions and an alternative approximation for the total electric field within
      the support of the investigated scatterer. Analytical (Mie) plane-wave scattering
      by a layered, circularly symmetric, lossy cylinder, and finite-difference time
      domain simulations involving plane-wave scattering by a more general, lossless
      phantom are utilized to compare the performance of the proposed method with that
      of the standard ODT techniques, which are based on the Born approximation and the
      Fourier diffraction theorem. Quantitative and qualitative superiority of the
      presented method is demonstrated. The proposed 2D technique can be readily
      extended to more realistic three-dimensional cases. With proper (cylindrical
      spherical) receiver configuration, the proposed method can be used without being
      confined to far-zone observations.

PMID- 19109599
TI  - Camera calibration for natural image studies and vision research.
AB  - A dominant theme in vision research is that important characteristics of the
      visual pathway evolved to be effective in processing natural scenes. Given this
      perspective, one can learn about the nature of visual processing from a
      quantitative analysis of natural images. Such analysis can benefit from the
      camera as a measuring device. As such, the camera should not introduce arbitrary
      artifacts into the image formation process. This paper describes how to correct a
      number of unnecessary artifacts associated with obtaining natural scene
      statistics with a digital camera. For artifacts that are inherently part of image
      formation, and where elimination is not possible or appropriate, we describe
      methods for transformation and quantification.

PMID- 19109600
TI  - Highly accurate reconstruction algorithm for bandwidth-limited signals and
      application to fringe signal recovery.
AB  - We present a bandwidth-limited signal reconstruction algorithm with high accuracy
      as a generalization of the conventional "self-truncating" method by using samples
      taken at a rate higher than the Nyquist rate. The extra sampling rate enables us
      to lower the truncation error by applying an appropriate window function that
      tapers the signal to be approximately limited in both the space and frequency
      domains up to exponentially small errors. The sampling theorem is used in the
      frequency domain for a space-limited signal to parameterize the tapered signal in
      terms of discrete samples in the frequency domain, which are determined by a
      least-squares fitting to handle both irregularly and regularly sampled data.
      Error analysis for the Gaussian and Kaiser window functions shows that the upper
      bounds of the errors for reconstructing the signal near the center of sampling
      decay exponentially in parameter qN faster than the error upper bound of the
      conventional "self-truncating" method, where q is the extra sampling rate
      relative to the Nyquist rate and 2N+1 is the number of samples used. We use
      simulation data to demonstrate the efficacy of this algorithm in reconstructing
      the fringe signals, which is crucial for the SIM (Space Interferometry Mission)
      PlanetQuest instrument calibration.

PMID- 19109601
TI  - Adaptive optics correction of segment aberration.
AB  - The objective of the present study is to estimate the ability of conventional
      adaptive optics (AO) to correct for a wavefront created by static errors randomly
      distributed over the population of a multisegmented primary mirror for an
      extremely large telescope (ELT). The criterion for the performance of AO is a
      correction factor: a ratio between two root-mean-square (RMS) values of the phase
      before and after the AO correction. We define a best value for the correction
      factor as the one obtained in an AO model described as a hard-edge high-pass
      filter applied to phase aberrations of the telescope pupil. We compare the
      results of other AO models with this best value. The relation between RMS and the
      power spectral density helps us evaluate the initial requirements of segment
      aberration for optimistic and pessimistic cases without need of specifying the
      type of AO. This work develops a tool that can be used for segment manufacturing
      specifications, for defining the requirements on an active optics system
      controlling segment shape, and for designing a high-contrast imaging instrument
      for an ELT.

PMID- 19109602
TI  - Deconvolution methods for image deblurring in optical coherence tomography.
AB  - Two-dimensional deconvolution methods are proposed to deblur optical coherence
      tomography images. One employs a two-dimensional deconvolution with a matrix
      given by the product of the longitudinal and transversal point-spread functions
      as its kernel, which can be taken as the general point-spread function of an
      optical coherence tomography system. The other uses two one-dimensional
      deconvolutions with the longitudinal and transversal point-spread functions
      successively. It is shown that the two deconvolution methods can deblur the
      experimentally obtained optical coherence tomography images effectively.

PMID- 19109603
TI  - Superlenses, metamaterials, and negative refraction.
AB  - The purpose of this paper is threefold. The first aim is to discuss the
      superlensing effect in left-handed material presented originally by Veselago
      [Sov. Phys. Usp.10, 509 (1968)] and Pendry [Phys. Rev. Lett.85, 3966 (2000)] for
      n=-1. Our discussion is based on an integral expression for the electromagnetic
      fields (i.e., the Extinction Theorem), and it allows us to demonstrate that such
      superlensing effect does not exist. The second aim is to discuss some basic
      questions about structured metamaterials formed by periodic resonator arrays. We
      will show that a set of antennas can never emulate a negative refractive index
      material. The third, concurrent, aim is to discuss the experimental evidence for
      negative refraction in structured periodic materials. We present another possible
      explanation of the experimental results concerning negative refraction that is
      based on the coherent interference of wavelets originated in the subwavelength
      structures.

PMID- 19109604
TI  - Centroid distortion of a wavefront with varying amplitude due to asymmetry in
      lens diffraction.
AB  - It is often of interest to measure the centroid of a light intensity pattern in
      order to deduce physical properties. Examples are the Hartmann-Shack sensor,
      which measures the wavefront slopes, and position sensors. We investigate whether
      amplitude changes of the incoming electromagnetic field can affect the location
      of the centroid, and we show that the effect is strongly dependent on the
      relative size of the diffraction pattern in relation to the lenslet size. We show
      that if the phase varies slowly in space-and the focal spot size relative to the
      centroid integration area approaches zero-this variation does not affect the
      centroid. This is a consequence of symmetry properties of the Fresnel operator.
      We then show that when the focal width is not infinitely small, changes in the
      field amplitude can exacerbate distortion of the centroid results.

PMID- 19109605
TI  - Analysis of radiation-mode coupling in reflective and transmissive tilted fiber
      Bragg gratings.
AB  - Radiation-mode coupling is stronger and more efficient in tilted fiber Bragg
      gratings than in other fiber gratings; it can be used to good advantage in such
      fields as optical communication and optical sensors. A simplified coupled-mode
      theory (CMT) approach to the analysis of radiation-mode coupling is proposed for
      what we believe to be the first time, whose validity and accuracy is demonstrated
      by comparing its simulation results with that of the complete CMT equations and
      the volume current method (VCM). With the simplified CMT approach, a theoretical
      spectral analysis of coupling from core mode to radiation modes in both
      reflective and transmissive tilted fiber Bragg gratings is presented. The
      influence of tilt angle on the transmission spectrum characteristics is
      comprehensively investigated. The different dependences between s-polarized and p
      polarized radiation-mode coupling on grating tilt angle are discussed, and an
      analysis is performed on how to obtain a high-performance in-fiber polarizer that
      involves a compromise between polarization extinction and insertion loss.

PMID- 19109606
TI  - Phase front retrieval by means of an iterative shadowgraphic method.
AB  - In this paper, we propose an iterative shadowgraphic method (ISM) as an
      interesting alternative to existing methods for self-referencing optical phase
      retrieval. Two defocused images of the intensity distribution of the light
      scattered by a weakly absorbing phase object were sufficient to retrieve the
      transverse phase distribution of the distorted illuminating beam. An algorithm
      was developed to correct for diffraction effects in phase maps retrieved with a
      simple shadowgraphic method. We provide a mathematical proof of the convergence
      of the algorithm to the true profile of the sought phase object. Several
      numerical tests were performed of the algorithm showing its capability of
      recovering the full details of the original phase distribution with increased
      resolution as compared with the simple shadowgraphic method. The convergence of
      the ISM was also compared numerically with that of a nonoptimized Gerchberg
      Saxton-type algorithm and found to be faster and not affected by stagnation
      problems.

PMID- 19109607
TI  - Self-calibration approach for optical long-baseline interferometry imaging.
AB  - Current optical interferometers are affected by unknown turbulent phases on each
      telescope. In the field of radio interferometry, the self-calibration technique
      is a powerful tool to process interferometric data with missing phase
      information. This paper intends to revisit the application of self-calibration to
      optical long-baseline interferometry (OLBI). We cast rigorously the OLBI data
      processing problem into the self-calibration framework and demonstrate the
      efficiency of the method on a real astronomical OLBI data set.

PMID- 19109608
TI  - Euclidean color-difference formula for small-medium color differences in log
      compressed OSA-UCS space.
AB  - This work continues previous research by the same authors [J. Opt. Soc. Am. A23,
      2077 (2006)], where empirical small-medium color differences were represented by
      an ellipsoidal equation DeltaEGP in the Uniform Color System of the Optical
      Society of America. Now logarithmic compressions on chroma and lightness are
      introduced to produce a new space with Euclidean color-difference formulas
      DeltaEE. The CIEDE2000, DeltaEGP, and DeltaEE formulas are found statistically
      equivalent in the prediction of many available empirical datasets. However,
      DeltaEE is the simplest formula providing relationships with visual processing.
      These analyses hold true for CIE 1964 Supplementary Standard Observer and D65
      illuminant.

PMID- 19109609
TI  - Bragg diffraction of multilayer volume holographic gratings under ultrashort
      laser pulse readout.
AB  - The multilayer coupled wave theory is extended to systematically investigate the
      diffraction properties of multilayer volume holographic gratings (MVHGs) under
      ultrashort laser pulse readout. Solutions for the diffracted and transmitted
      intensities, diffraction efficiency, and the grating bandwidth are obtained in
      transmission MVHGs. It is shown that the diffraction characteristics depend not
      only on the input pulse duration but also on the number and thickness of grating
      layers and the gaps between holographic layers. This analysis can be implemented
      as a useful tool to aid with the design of multilayer volume grating-based
      devices employed in optical communications, pulse shaping, and processing.

PMID- 19109610
TI  - Hollow vortex beams.
AB  - Hollow beam formation of radially and azimuthally polarized vortex beams, which
      has arbitrary topological charge, is analytically discussed under the strong
      focusing condition. The expressions for the electric fields of the focused vector
      vortex beams are obtained based on a vector diffraction theory. The order of the
      Bessel function of the first kind appearing in the expressions indicates the
      ability to form hollow beams. Similar discussion is applied for different vortex
      beams, which are expressed by linear combination of radially and azimuthally
      polarized beams. Calculations of intensity profiles across the focus are also
      presented.

PMID- 19109611
TI  - Spatial coherence modulation.
AB  - The principles of amplitude and phase modulation of the spatial coherence of the
      optical field are discussed. They are based on the modification of the phase
      space diagram of the field, provided by the marginal power spectrum, which allows
      synthesis of the modulating functions of the spatial coherence and the
      corresponding complex transmissions to be transferred onto a spatial light
      modulator for application purposes. Numerical and experimental results are
      presented. This novel technique can be applied in designing specific shapes of
      power distributions.

PMID- 19109612
TI  - Numerical scattering analysis of TE plane waves by a metallic diffraction grating
      with local defects.
AB  - We consider the numerical scattering of plane waves by a metallic diffraction
      grating with a single defect. Besides different diffracted orders, a perturbed
      scattered field with arbitrary reflection direction is generated by the defect.
      We transform the diffraction grating into a closed waveguide by introducing a
      perfectly matched layer. The diffracted field is solved by applying
      pseudoperiodic boundary conditions on cell boundaries. Then we take two steps to
      resolve the perturbed scattered field. On the defect cell it is obtained by
      solving the governing wave equation with absorbing boundary conditions derived by
      a fast recursive doubling procedure. On the rest of the domain the perturbed
      scattered field is computed by using the recursive matrix operators efficiently.
      An optical theorem is employed to evaluate the proposed method.

PMID- 19109613
TI  - Hue and saturation shifts from spatially induced blackness.
AB  - We studied changes in the color appearance of a chromatic stimulus as it
      underwent simultaneous contrast with a more luminous surround. Three normal
      trichromats provided color-naming descriptions for a 10 cd/m2 monochromatic field
      while a broadband white annulus surround ranged in luminance from 0.2 cd/m2 to
      200 cd/m2. Descriptions of the chromatic field included Red, Green, Blue, Yellow,
      White, and Black or their combinations. The naming frequencies for each
      color/surround were used to calculate measures of similarity among the stimuli.
      Multidimensional scaling analysis of these subjective similarities resulted in a
      four-dimensional color space with two chromatic axes, red-green and blue-yellow,
      and two achromatic axes, revealing separate qualities of blackness/lightness and
      saturation. Contrast-induced darkening of the chromatic field was found to be
      accompanied by shifts in both hue and saturation. Hue shifts were similar to the
      Bezold-Brucke shift; shifts in saturation were also quantified. A stage model is
      proposed to account for the relationships among blackness induction and the
      inherent nonlinearities in chromatic and achromatic processing.

PMID- 19109614
TI  - Rotation of absorbing spheres in Laguerre-Gaussian beams.
AB  - It is well known that optical vortex beams carry orbital as well as spin angular
      momentum. This optical angular momentum can manifest itself mechanically, for
      example in tightly focused Laguerre-Gaussian beams, where trapped, weakly
      absorbing spheres rotate at a rate proportional to the total angular momentum
      carried by the beam. In the present paper we subject this system to a rigorous
      analysis involving expansions in vector spherical wave functions that culminates
      in a simple expression for the torque on the sphere. It is seen that, for large
      weakly absorbing spheres, the induced torque per unit power is independent of the
      detailed structure of the incident field, being a simple function of two indices
      that describe the helicity and polarization state of the beam, the relative
      refractive indices of the sphere and ambient medium, the absorption index of the
      sphere, and its radius. A number of relationships between the coefficients of
      these expansions are also developed.

PMID- 19109615
TI  - Comparison of transition-matrix sampling procedures.
AB  - We compare the accuracy of the multicanonical procedure with that of transition
      matrix models of static and dynamic communication system properties incorporating
      different acceptance rules. We find that for appropriate ranges of the underlying
      numerical parameters, algorithmically simple yet highly accurate procedures can
      be employed in place of the standard multicanonical sampling algorithm.

PMID- 19109616
TI  - Beam propagation modeling of modified volume Fresnel zone plates fabricated by
      femtosecond laser direct writing.
AB  - Light diffraction by volume Fresnel zone plates (VFZPs) is simulated by the
      Hankel transform beam propagation method (Hankel BPM). The method utilizes
      circularly symmetric geometry and small step propagation to calculate the
      diffracted wave fields by VFZP layers. It is shown that fast and accurate
      diffraction results can be obtained with the Hankel BPM. The results show an
      excellent agreement with the scalar diffraction theory and the experimental
      results. The numerical method allows more comprehensive studies of the VFZP
      parameters to achieve higher diffraction efficiency.

PMID- 19109617
TI  - Calculation and correction of piston phase aberration in synthesis imaging.
AB  - The principle of redundant spacings calibration has previously been described for
      the purpose of calibrating piston phase aberration affecting elements of a dilute
      aperture array using a system of linear equations in terms of the aperture phases
      as well as object phase information. Here we develop matrices for the correction
      of piston phase aberration by use of image sharpness and also by phase retrieval.
      These are both presented in wavefront sensor formulation in order to draw analogy
      between the approaches. We then discuss solution ambiguity affecting both methods
      and describe array design criteria to prevent such ambiguity. The problem of
      increased image aliasing under image sharpness correction is also highlighted.

PMID- 19109618
TI  - Overcoming turbulence-induced space-variant blur by using phase-diverse speckle.
AB  - Space-variant blur occurs when imaging through volume turbulence over
      sufficiently large fields of view. Space-variant effects are particularly severe
      in horizontal-path imaging, slant-path (air-to-ground or ground-to-air)
      geometries, and ground-based imaging of low-elevation satellites or astronomical
      objects. In these geometries, the isoplanatic angle can be comparable to or even
      smaller than the diffraction-limited resolution angle. We report on a
      postdetection correction method that seeks to correct for the effects of space
      variant aberrations, with the goal of reconstructing near-diffraction-limited
      imagery. Our approach has been to generalize the method of phase-diverse speckle
      (PDS) by using a physically motivated distributed-phase-screen model. Simulation
      results are presented that demonstrate the reconstruction of near-diffraction
      limited imagery under both matched and mismatched model assumptions. In addition,
      we present evidence that PDS could be used as a beaconless wavefront sensor in a
      multiconjugate adaptive optics system when imaging extended scenes.

PMID- 19109619
TI  - Tomographic reconstruction for wide-field adaptive optics systems: Fourier domain
      analysis and fundamental limitations.
AB  - Several wide-field-of-view adaptive optics (WFAO) concepts such as multi
      conjugate AO (MCAO), multi-object AO (MOAO), and ground-layer AO (GLAO) are
      currently being studied for the next generation of Extremely Large Telescopes
      (ELTs). All these concepts will use atmospheric tomography to reconstruct the
      turbulent-phase volume. In this paper, we explore different reconstruction
      algorithms and their fundamental limitations, conducting this analysis in the
      Fourier domain. This approach allows us to derive simple analytical formulations
      for the different configurations and brings a comprehensive view of WFAO
      limitations. We then investigate model and statistical errors and their effect on
      the phase reconstruction. Finally, we show some examples of different WFAO
      systems and their expected performance on a 42 m telescope case.

PMID- 19109620
TI  - Effect of phosphor geometry on the luminous efficiency of high-power white light
      emitting diodes with excellent color rendering property.
AB  - High-power white light-emitting diodes (LEDs) are fabricated by combining blue
      LEDs and green (Ba,Sr)(2)SiO(4):Eu(2+) and red CaAlSiN(3):Eu(2+) phosphors with
      varying phosphor geometry. The white LED having separated the phosphor layer by
      the silicone gel layer between green and red phosphor layers shows superior
      optical properties. The luminous efficiency (eta(L)) is improved by a decrease of
      reabsorption of green light by red phosphor owing to a difference among
      refractive indices. The white LED shows very high eta(L) of 51 lm/W and a high
      color rendering index of 95 under 350 mA. In addition, improved luminous
      properties of the white LED including a separated phosphor layer are confirmed
      via ray-trace simulation.

PMID- 19109621
TI  - Extraordinary optical transmission through hole arrays in optically thin metal
      films.
AB  - A theoretical study is presented on the optical transmission through square hole
      arrays drilled in optically thin films, where transmission may occur through both
      the holes and the metal layer. It is shown that, as the thickness of the metal
      film decreases, the coupling of light with short-range surface plasmons redshifts
      the extraordinary optical transmission peak to longer wavelengths. At the same
      time, the maximum-to-minimum transmittance ratio is kept high even for metal
      thicknesses as small as one skin depth.

PMID- 19109622
TI  - Optical ensemble analysis of intraocular lens performance through a simulated
      clinical trial with ZEMAX.
AB  - A ZEMAX model was constructed to simulate a clinical trial of intraocular lenses
      (IOLs) based on a clinically oriented Monte Carlo ensemble analysis using
      postoperative ocular parameters. The purpose of this model is to test the
      feasibility of streamlining and optimizing both the design process and the
      clinical testing of IOLs. This optical ensemble analysis (OEA) is also validated.
      Simulated pseudophakic eyes were generated by using the tolerancing and
      programming features of ZEMAX optical design software. OEA methodology was
      verified by demonstrating that the results of clinical performance simulations
      were consistent with previously published clinical performance data using the
      same types of IOLs. From these results we conclude that the OEA method can
      objectively simulate the potential clinical trial performance of IOLs.

PMID- 19109623
TI  - Generation of vortex array beams from a thin-slice solid-state laser with shaped
      wide-aperture laser-diode pumping.
AB  - We demonstrate vortex array-beam generations from a thin-slice, wide-aperture,
      solid-state laser with laser-diode end-pumping. Radial and rectangular vortex
      arrays were found to be formed in a controlled fashion with symmetric and
      asymmetric pump-beam profiles, respectively. Most of these vortices exhibited
      single-frequency oscillations arising from a spontaneous process of transverse
      mode locking of degenerate or nearly degenerate modes assisted by the laser
      nonlinearity. Single-frequency rectangular array beams consisting of a large
      number of vortices, e.g., closely packed 25, 36, or 46 vortex pixels, were
      generated, originating from Ince-Gaussian modes excited by the asymmetric
      pumping.

PMID- 19109624
TI  - Paraxial group.
AB  - We introduce the paraxial group, the group of symmetries of the paraxial-wave
      equation and its action on paraxial beams. The transformations, elements of the
      group, are used to obtain closed-form expressions for the propagation of any
      paraxial beam through misaligned ABCD optical systems. We prove that any paraxial
      beam is form-invariant under these transformations.

PMID- 19109625
TI  - Enhancing extraordinary transmission of light through a metallic nanoslit with a
      nanocavity antenna.
AB  - The extraordinary transmission of light through a vertical nanoslit in a metal
      film is enhanced by introducing a nanocavity antenna formed by a nearby metallic
      nanostrip over the slit opening. For a fixed wavelength, the width of the
      metallic nanostrip should be chosen to make the horizontal metal-insulator-metal
      waveguide of finite length resonant as a Fabry-Perot cavity. When such a cavity
      antenna is used to enhance the transmission through a nonresonant nanoslit, the
      slit should be opened at a position with a maximal magnetic field in the
      horizontal resonant cavity. It is shown that an optimized cavity antenna can
      enhance greatly the transmission of light through a nonresonant nanoslit (by
      about 20 times) or a resonant nanoslit (by 124%). Such a transmission enhancement
      with a nanocavity antenna is studied for the first time, and the physical
      mechanism is explained.

PMID- 19109626
TI  - Negative-index bianisotropic photonic metamaterial fabricated by direct laser
      writing and silver shadow evaporation.
AB  - We present the blueprint for a novel negative-index metamaterial. This structure
      is fabricated via three-dimensional two-photon direct laser writing and silver
      shadow evaporation. The comparison of measured linear optical spectra with theory
      shows good agreement and reveals a negative real part of the refractive index at
      around 3.85 microm wavelength -- despite the fact that the metamaterial structure
      is bianisotropic owing to the lack of inversion symmetry along its surface
      normal.

PMID- 19109627
TI  - Adaptive optimization of a hologram in holographic femtosecond laser processing
      system.
AB  - In holographic parallel laser processing, precise control of diffraction peaks is
      important for fabricating enormous numbers of nanometer-scale structures.
      Although an optimized hologram has high uniformity of the peaks in a computer
      reconstruction, in practice, the uniformity is decreased owing to the spatial
      properties of the optical system. A novel optimization method based on peak
      intensity measurement is proposed to improve the uniformity. The method
      automatically incorporates the properties of the optical system into the
      hologram. Improved holographic femtosecond laser processing with this adaptive
      optimization is demonstrated.

PMID- 19109628
TI  - Resonant tunneling effects on cavity-embedded metal film caused by surface
      plasmon excitation.
AB  - We investigate cavity-modulated resonant tunneling through a silver film with
      periodic grooves on both surfaces. A strip cavity embedded in the film affects
      tunneling frequencies via a coupling mode and waveguide mode. In the coupling
      mode, both the resonant tunneling through the gap between the groove and the
      cavity and the cavity itself form an entire resonant structure. In the waveguide
      mode, however, the cavity functions as a surface-plasmon waveguide. Hence,
      tunneling frequencies are close to resonant absorption frequencies of the groove
      structure and are irrelevant to cavity properties.

PMID- 19109629
TI  - Ion-implanted optical channel waveguides in neodymium-doped yttrium aluminum
      garnet transparent ceramics for integrated laser generation.
AB  - We report, for the first time to our knowledge, on the fabrication of optical
      channel waveguides in neodymium-doped yttrium aluminum garnet transparent
      ceramics by oxygen implantation. The fabricated waveguides show reduced
      propagation losses (1.5 dB/cm), as well as the possibility of waveguide-mode
      tailoring. The confocal fluorescence images of the channel waveguides reveal that
      oxygen implantation causes only slight changes in the fluorescence properties of
      neodymium ions making the fabricated structures promising candidates for
      integrated laser sources in the infrared bands.

PMID- 19109630
TI  - Generation of 210 fs laser pulses at 1093 nm by a self-starting mode-locked
      Yb:GYSO laser.
AB  - We report the first demonstration, to our knowledge, of the femtosecond laser
      operation by using a new alloyed Yb:GYSO crystal as the gain medium. With a 5 at.
      %Yb(3+)-doped sample and chirped mirrors for dispersion compensation, we obtained
      pulses as short as 210 fs at the center wavelength of 1093 nm. The average mode
      locking power is 300 mW, and the pulse repetition frequency is 80 MHz.

PMID- 19109631
TI  - Mode purities of Laguerre-Gaussian beams generated via complex-amplitude
      modulation using phase-only spatial light modulators.
AB  - We investigate output mode purities of Laguerre-Gaussian (LG) beams generated
      from four typical simultaneous amplitude and phase modulation methods with phase
      only spatial light modulators (SLMs). Numerical simulations supposing the
      practical SLM, i.e., stepwise phase modulation with a pixelated device, predict
      an output mode purity of beyond 0.969 for the LG beams of less than radially and
      azimuthally fifth order. Experimental results of generating LG beams are also
      shown to demonstrate the effects of the simultaneous phase and amplitude
      modulation.

PMID- 19109632
TI  - High-resolution surface-plasmon resonance real-time imaging.
AB  - We use surface-plasmon resonance in a silver film to obtain high-resolution real
      time images of a transparent dielectric sample in contact with it. A new aspect
      of the work was the use of radially polarized illumination from a LED at 530 nm
      to obtain speckle-free images with high spatial resolution along all
      orientations. The sensitivity to refractive index changes in the sample is
      estimated to be better than 10(-3), and the modulation transfer function out to
      spatial frequency 1 microm(-1) was measured.

PMID- 19109633
TI  - Phase Fresnel lens recorded in photo-thermo-refractive glass by selective
      exposure to infrared ultrashort laser pulses.
AB  - A new two-step approach for fabricating phase optical elements in photo-thermo
      refractive glass by exposure to IR ultrashort laser pulses followed by thermal
      development is shown. A binary phase Fresnel lens was designed to focus light at
      632.8 nm to a focal length of 400 cm. Conditions of ultrashort pulse irradiation
      and thermal development were chosen to achieve pi phase shift between zone
      boundaries. The focusing efficiency of the element was measured to be close to
      50%.

PMID- 19109634
TI  - Complex-variable-function-Gaussian solitons.
AB  - We have introduced a novel (to our knowledge) class of complex-variable-function
      (CVF)-Gaussian solitons that constitute the exact soliton solutions of the Snyder
      Mitchell model. The CVF-Gaussian solitons whose transverse structure has an
      inherent rotation are the product of an arbitrary analytic CVF and a Gaussian
      function. A distribution factor that is the parameter for the description of the
      transverse distribution of the CVF-Gaussian solitons is discussed.

PMID- 19109635
TI  - Compact Brillouin-erbium fiber laser.
AB  - A single-wavelength Brillouin fiber laser (BFL) is demonstrated at the extended L
      band region using bismuth-based erbium-doped fiber (Bi-EDF) for the first time to
      the best of our knowledge. A 2.15-m-long Bi-EDF is used to provide both nonlinear
      and linear gains to generate a stimulated Brillouin scattering (SBS) and to
      amplify the generated SBS, respectively. The BFL operates at 1613.93 nm, which is
      upshifted by 0.09 nm from the Brillouin pump with a peak power of 2 dBm and a
      side-mode suppression ratio of more than 22 dB. The generated BFL has a narrow
      linewidth and many potential applications, such as in optical communication and
      sensors.

PMID- 19109636
TI  - Small third-order optical-nonlinearity detection free of laser parameters.
AB  - We demonstrate a novel, versatile method for sensitive measurement of nonresonant
      third-order optical nonlinearities in waveguides. The measurement is referenced
      to a bulk sample with well-known nonlinear optical properties, thus ruling out
      the influence of laser pulse parameters like duration, contrast, and spectral
      phase or amplitude. Since the generated mixing product is heterodyne detected,
      extremely small third-order optical nonlinearities, e.g., from air-filled short
      waveguides, can be measured.

PMID- 19109637
TI  - High-speed measurement of free spectral range voltage of tunable filters.
AB  - A new technique to measure the frequency response of a fiber-optic tunable filter
      (TF) is proposed and demonstrated. This technique is based on the linearity of
      the sinusoidal function in the vicinity of mpi, where m is an integer. The free
      spectral range (FSR) voltage, V(FSR), is evaluated fast and accurately by
      measuring the time interval corresponding to the bandwidth of TF. The time
      interval is obtained by adjusting the dc offset of the driving signal to locate
      the transmission peak of TF at the maximum slope of the driving signal of <1V(p
      p). The measured FSR voltages range from 500 mV to 100 V over the frequency up to
      200 kHz.

PMID- 19109638
TI  - Tunable narrowband entangled photon pair source for resonant single-photon single
      atom interaction.
AB  - We present a tunable, frequency-stabilized, narrow-bandwidth source of frequency
      degenerate, entangled photon pairs. The source is based on spontaneous parametric
      downconversion in periodically poled KTiOPO(4). Its wavelength can be stabilized
      to 850 or 854 nm, thus allowing to address two transitions in (40)Ca(+) ions. Its
      output bandwidth of 22 MHz coincides with the absorption bandwidth of the calcium
      ions. Its spectral power density is 1.0 generated pairs/(s MHz mW).

PMID- 19109639
TI  - All-optical regenerative NRZ-OOK-to-RZ-BPSK format conversion using silicon
      waveguides.
AB  - We propose a scheme to achieve regenerative format conversion from a distorted
      non-return-to-zero-on-off-keying (NRZ-OOK) signal to a return-to-zero-binary
      phase-shift-keying (RZ-BPSK) signal of high quality in an integrated device. This
      proposal is achieved by employing an interferometer on a silicon chip with a
      coupled ring resonator optical waveguide embedded in one arm. In this scheme the
      amplified NRZ-OOK signal is injected into the converter together with a locally
      generated return-to-zero (RZ) pulse train at a different wavelength. Owing to the
      linear and nonlinear effects in the silicon waveguides, the RZ pulse train
      changes to a clean RZ-BPSK signal after it is cross modulated by the NRZ-OOK
      signal. To verify the feasibility of our scheme, we simulate the conversion at 10
      Gbits/s.

PMID- 19109640
TI  - Extracting hysteresis from nonlinear measurement of wavefront-sensorless adaptive
      optics system.
AB  - In many scientific and medical applications wavefront-sensorless adaptive optics
      (AO) systems are used to correct the wavefront aberration by optimizing a certain
      target parameter, which is nonlinear with respect to the control signal to the
      deformable mirror (DM). Hysteresis is the most common nonlinearity of DMs, which
      can be corrected if the information about the hysteresis behavior is present. We
      report a general approach to extract hysteresis from the nonlinear behavior of
      the adaptive optical system, with the illustration of a Foucault knife test,
      where the voltage-intensity relationship consists of both hysteresis and some
      memoryless nonlinearity. The hysteresis extracted here can be used for modeling
      and linearization of the AO system.

PMID- 19109641
TI  - Decomposition of shading and reflectance from a texture image.
AB  - A method for decomposing shading and reflectance components from a color texture
      image is presented. The shading intensity of each pixel is either computed or
      synthesized according to its characteristics, and the reflectance is consequently
      decomposed, with additional denoising when necessary. The performance of the
      proposed method is evaluated using real color texture images.

PMID- 19109642
TI  - Evolutionary algorithm for solving the inverse problem of finding the incident
      field on a high-aperture lens for generating a desired focused field.
AB  - Using a proposed evolutionary algorithm, we have solved the inverse problem of
      finding the incident field on a high-aperture lens for generating a desired
      focused field, for the first time (to our knowledge). Further, we have achieved
      the global solution to the problem using this novel algorithm.

PMID- 19109643
TI  - Compensation of reflectance response deviations of guided-mode resonant filters
      induced by overetching fabrication.
AB  - Unless the fabrication error control is well treated, it easily causes overetched
      fabrication errors, which causes the resonant peak value deviation during the
      fabrication process of guided-mode resonant filters (GMRFs). Hence, the
      fabrication error control becomes a key point for improving the performance of
      GMRF. We find that, within the range of the groove depth from 93 to 105 nm, the
      relationship between the overetched error and the resonant peak value deviation
      is nearly linear, which means that we can compensate the reflectance response
      deviation and reduce the resonant peak value deviation by the method of covering
      the layer film on the GMRF. Simulation results show that the deviation is
      compensated perfectly by this way.

PMID- 19109644
TI  - Indirect synthesis of interference terms in digital holography.
AB  - We propose a numerical wavefront manipulation method for synthesizing a new
      interference term from two digital holograms recorded using the same reference
      wavefront. The interference term of interest is synthesized indirectly, and its
      reconstructed image is unaffected by the reference wavefront used during hologram
      recording. We present experimental results of the indirect synthesis of the
      interference term corresponding to the lensless Fourier hologram using the
      Fresnel hologram.

PMID- 19109645
TI  - Optical refractometer based on a birefringent Bragg grating written in an H
      shaped fiber.
AB  - An optical refractometer based on a birefringent (Hi-Bi) fiber Bragg grating
      (FBG) written in a new H-shaped fiber structure is proposed. This structure is
      formed by opening the two holes of a side-hole fiber using chemical etching. When
      the Hi-Bi FBG is immersed in different liquids, different responses of the slow
      and fast wavelengths are obtained. The refractometer is also capable of
      simultaneous measurement of refractive index and temperature.

PMID- 19109646
TI  - High-resolution three-dimensional tomographic diffractive microscopy of
      transparent inorganic and biological samples.
AB  - We have developed a tomographic diffractive microscope, equipped with a
      fluorescence confocal scanner. We measure experimentally the lateral resolution
      using an edge method and by comparing tomographic images of the same samples with
      wide-field and laser scanning confocal microscopy images; a scanning electron
      microscope image serves as a reference. The experimental resolution is shown to
      be to about 130 nm, or lambda/(3.5 NA). This instrument also permits one to
      measure 3D, complex index of refraction distributions, a quantity that is not
      accessible to conventional microscopes, and we show how this feature may be used
      to observe KCl crystals, absorption of which is very weak.

PMID- 19109647
TI  - Plasma-blueshift spectral shear interferometry for characterization of ultimately
      short optical pulses.
AB  - We introduce a bandwidth-unlimited, dispersion- and shear-self-calibrated, timing
      jitter-free pulse measurement technique based on a quasi-linear temporal phase
      modulation in a gas weakly ionized by a long pump pulse. Results of a 5 fs pulse
      characterization are reported.

PMID- 19109648
TI  - Generation of a 20 GHz train of subpicosecond pulses with a stabilized optical
      frequency-comb generator.
AB  - With a modulator-based 10 GHz optical-frequency-comb generator at 1.55 microm, we
      report a 20 GHz repetitive train of optical pulses as short as 450 fs. The timing
      stability of the 20 GHz pulses, in addition to the phase for optical-comb modes,
      shows a strong dependence on the relative frequency detuning between the comb
      generator's cavity and the seed cw laser. With a new and simple scheme, the comb
      generator's cavity resonance was locked to a narrow-linewidth seed laser within
      an estimated optical-frequency range < or = 6 MHz, enabling high-fidelity 20 GHz
      subpicosecond pulses and stable optical-frequency-comb generation for indefinite
      periods.

PMID- 19109649
TI  - Experimental observation of subwavelength localization using metamaterial-based
      cavities.
AB  - We report subwavelength localization of electromagnetic fields within cavities
      based on metamaterials. Cavity resonances are observed in the transmission
      spectrum of a split-ring resonator and composite metamaterials cavity structures.
      These cavity resonances are shown to exhibit high-quality factors. Since the unit
      cells of metamaterials are much smaller than the operation wavelength,
      subwavelength localization is possible within these metamaterial cavity
      structures. In the present Letter, we show that the electromagnetic field is
      localized into a region of lambda/8, where lambda is the cavity resonance
      wavelength.

PMID- 19109650
TI  - Normal modes for plasmonic nanolasers with dispersive and inhomogeneous media.
AB  - We derive the quasi-orthogonality condition of optical modes in a dispersive and
      inhomogeneous medium. This condition leads to the proper normalization rule of
      the optical field in a general linear medium with inhomogeneity. The derived rule
      also provides a physically meaningful method in estimating the magnitude of the
      field-enhanced spontaneous and stimulated emission rates, for example, in a
      microcavity or nanocavity.

PMID- 19109651
TI  - Sustainability of exercise-induced increases in bone density and skeletal
      structure.
AB  - BACKGROUND: The prevalence of osteoporosis with related fragility fractures has
      increased during the last decades. As physical activity influences the skeleton
      in a beneficial way, exercise may hypothetically be used as a prophylactic tool
      against osteoporosis. OBJECTIVE: This review evaluates if exercise-induced
      skeletal benefits achieved during growth remain in a long-term perspective.
      DESIGN: PUBLICATIONS WITHIN THE FIELD WERE SEARCHED THROUGH MEDLINE (PUBMED)
      USING THE SEARCH WORDS: exercise, physical activity, bone mass, bone mineral
      content (BMC), bone mineral density (BMD) and skeletal structure. We based our
      inferences on publications with the highest level of evidence, particularly
      randomised controlled trials (RCT). RESULTS: Benefits in BMD achieved by exercise
      during growth seem to be eroded at retirement, but benefits in skeletal structure
      may possibly be retained in a longer perspective. Recreational exercise seems to
      at least partially maintain exercise-induced skeletal benefits achieved during
      growth. CONCLUSIONS: Exercise during growth may be followed by long-term
      beneficial skeletal effects, which could possibly reduce the incidence of
      fractures. Exercise during adulthood seems to partly preserve these benefits and
      reduce the age-related bone loss.

PMID- 19109653
TI  - Observed dietary intake in adults with intellectual disability living in the
      community.
AB  - BACKGROUND: Knowledge is lacking about dietary habits among people with
      intellectual disability (ID) living in community residences under new living
      conditions. OBJECTIVE: To describe the dietary habits of individuals with ID
      living in community residences, focusing on intake of food, energy and nutrients
      as well as meal patterns. DESIGN: Assisted food records and physical activity
      records over a 3-day observation period for 32 subjects. RESULTS: Great variation
      was observed in daily energy intake (4.9-14 MJ) dispersed across several meals,
      with on average 26% of the energy coming from in-between-meal consumption. Main
      energy sources were milk products, bread, meat products, buns and cakes. The
      daily intake of fruit and vegetables (320+/-221 g) as well as dietary fiber (21+/
      9.6 g) was generally low. For four vitamins and two minerals, 19-34% of subjects
      showed an intake below average requirement (AR). The physical activity level
      (PAL) was low for all individuals (1.4+/-0.1). CONCLUSION: A regular meal pattern
      with a relatively high proportion of energy from in-between-meal eating occasions
      and a low intake of especially fruits were typical of this group of people with
      ID. However, the total intake of energy and other food items varied a great deal
      between individuals. Thus, every adult with ID has to be treated as an individual
      with specific needs. A need for more knowledge about food in general and
      particularly how fruit and vegetables could be included in cooking as well as
      encouraged to be eaten as in-between-meals seems imperative in the new living
      conditions for adults with ID.

PMID- 19109652
TI  - Physical activity increases bone mass during growth.
AB  - BACKGROUND: The incidence of fragility fractures has increased during the last
      half of the 1990's. One important determinant of fractures is the bone mineral
      content (BMC) or bone mineral density (BMD), the amount of mineralised bone. If
      we could increase peak bone mass (the highest value of BMC reached during life)
      and/or decrease the age-related bone loss, we could possibly improve the skeletal
      resistance to fracture. OBJECTIVE: This review evaluates the importance of
      exercise as a strategy to improve peak bone mass, including some aspects of
      nutrition. DESIGN: PUBLICATIONS WITHIN THE FIELD WERE SEARCHED THROUGH MEDLINE
      (PUBMED) USING THE SEARCH WORDS: exercise, physical activity, bone mass, bone
      mineral content, bone mineral density, BMC, BMD, skeletal structure and
      nutrition. We included studies dealing with exercise during growth and young
      adolescence. We preferably based our inferences on randomised controlled trials
      (RCT), which provide the highest level of evidence. RESULTS: Exercise during
      growth increases peak bone mass. Moderate intensity exercise intervention
      programs are beneficial for the skeletal development during growth. Adequate
      nutrition must accompany the exercise to achieve the most beneficial skeletal
      effects by exercise. CONCLUSION: Exercise during growth seems to enhance the
      building of a stronger skeleton through a higher peak bone mass and a larger bone
      size.

PMID- 19109654
TI  - Fatty acids in bovine milk fat.
AB  - Milk fat contains approximately 400 different fatty acid, which make it the most
      complex of all natural fats. The milk fatty acids are derived almost equally from
      two sources, the feed and the microbial activity in the rumen of the cow and the
      lipids in bovine milk are mainly present in globules as an oil-in-water emulsion.
      Almost 70% of the fat in Swedish milk is saturated of which around 11% comprises
      short-chain fatty acids, almost half of which is butyric acid. Approximately 25%
      of the fatty acids in milk are mono-unsaturated and 2.3% are poly-unsaturated
      with omega-6/omega-3 ratio around 2.3. Approximately 2.7% are trans fatty acids.

PMID- 19109655
TI  - Plant sterols/stanols as cholesterol lowering agents: A meta-analysis of
      randomized controlled trials.
AB  - BACKGROUND: Consumption of plant sterols has been reported to reduce low density
      lipoprotein (LDL) cholesterol concentrations by 5-15%. Factors that affect plant
      sterol efficacy are still to be determined. OBJECTIVES: To more precisely
      quantify the effect of plant sterol enriched products on LDL cholesterol
      concentrations than what is reported previously, and to identify and quantify the
      effects of subjects' characteristics, food carrier, frequency and time of intake
      on efficacy of plant sterols as cholesterol lowering agents. DESIGN: Fifty-nine
      eligible randomized clinical trials published from 1992 to 2006 were identified
      from five databases. Weighted mean effect sizes were calculated for net
      differences in LDL levels using a random effect model. RESULTS: Plant sterol
      containing products decreased LDL levels by 0.31 mmol/L (95% CI, -0.35 to -0.27,
      P= < 0.0001) compared with placebo. Between trial heterogeneity was evident (Chi
      square test, P = <0.0001) indicating that the observed differences between trial
      results were unlikely to have been caused by chance. Reductions in LDL levels
      were greater in individuals with high baseline LDL levels compared with those
      with normal to borderline baseline LDL levels. Reductions in LDL were greater
      when plant sterols were incorporated into fat spreads, mayonnaise and salad
      dressing, milk and yoghurt comparing with other food products such as croissants
      and muffins, orange juice, non-fat beverages, cereal bars, and chocolate. Plant
      sterols consumed as a single morning dose did not have a significant effect on
      LDL cholesterol levels. CONCLUSION: Plant sterol containing products reduced LDL
      concentrations but the reduction was related to individuals' baseline LDL levels,
      food carrier, and frequency and time of intake.

PMID- 19109656
TI  - Whole grain rye porridge breakfast improves satiety compared to refined wheat
      bread breakfast.
AB  - BACKGROUND: Previous studies show that dietary fibre-rich foods with low energy
      density have a stronger effect on satiety per calorie compared to more energy
      dense foods. OBJECTIVE: To investigate subjective appetite and voluntary energy
      intake (24 h) after consumption of rye porridge breakfast and pasta lunch made
      from whole grain compared to iso-energetic reference meals made from refined
      cereals: wheat bread breakfast and wheat pasta lunch. SUBJECTS: In all, 22
      healthy subjects, 14 females and 8 males, aged 21-64 years, BMI ranging from 18.7
      to 27.5 kg/m(2), participated. DESIGN: A randomised, crossover design was used.
      Appetite was rated by visual analogue scales (VAS) regularly from just before
      breakfast (08:00) until bedtime. An ad libitum dinner was served at 16:00. After
      leaving the clinic and in the morning day 2, subjects recorded foods consumed.
      RESULTS: Whole grain rye porridge gave a significantly prolonged satiety, lowered
      hunger and desire to eat (p<0.05 in most point estimates) up to 8 h after
      consumption compared to the refined wheat bread. The two pasta lunch meals did
      not vary in their effects on appetite ratings. There was no significant effect on
      ad libitum energy intake at 16:00 or self-reported energy and macronutrient
      intake in the evening and breakfast meal on day 2. CONCLUSIONS: Whole grain rye
      porridge at breakfast has prolonged satiating properties up to 8 h after
      consumption compared to refined wheat bread, but did not diminish subsequent food
      intake.

PMID- 19109657
TI  - A two-year clinical lifestyle intervention program for weight loss in obesity.
AB  - BACKGROUND: In recent randomised prospective studies, lifestyle intervention
      induced a weight loss of approximately 5%. OBJECTIVE: To describe and evaluate a
      2-year on-going group intervention program in clinical practice in terms of
      weight loss and changes in metabolic risk factors, i.e. sagital abdominal
      diameter (SAD), triglycerides, fasting blood glucose and blood pressure. DESIGN:
      The aim of the intervention program was to motivate lifestyle changes concerning
      food intake and physical activity. The emphasis was on lifestyle modification,
      followed up at regular visits during 2 years. Subjects evaluated were 100 women
      with mean BMI 37.6 kg/m(2) and 26 men with mean BMI 36.5 kg/m(2). RESULTS: One
      hundred of 151 enrolled women and 26 of 36 men completed the program. Mean weight
      decreased by 3.8 kg in women (from 103.5 to 99.7, p<0.001) and 4.4 kg in men
      (from 116.5 to 112.1, p<0.05), respectively. SAD decreased by 5% (p=0.001 in
      women, p=0.01 in men), and triglycerides by 16% in women (p=0.01) and 24% in men
      (p=0.001), however systolic and diastolic blood pressure increased slightly but
      significantly. CONCLUSION: It is possible to perform a clinical lifestyle
      intervention program for outpatients on an ongoing basis with weight loss,
      lowered SAD and triglycerides, and a similar or lower dropout rate compared to
      clinical trials.

PMID- 19109658
TI  - Calcium intake in elderly patients with hip fractures.
AB  - BACKGROUND: Dietary calcium intake is assumed important in the prevention and
      treatment of osteoporosis. However, people in countries with a high calcium
      intake from commodities such as milk and milk products have a high incidence of
      hip fracture. The effect and influence of calcium intake in the prevention of
      osteoporotic fracture vary from different studies. OBJECTIVE: To investigate
      premorbid daily calcium intake in patients with low energy hip fractures during
      four consecutive years. DESIGN: In total 120 patients (mean age 78+/-8.5 (SD)
      years) were included between 2002 and 2005. The patients answered a structured
      food frequency questionnaire (FFQ) and interviews on patients' daily calcium
      intake from food and supplements took place during a 6-month period before the
      fracture. Dual energy X-ray absorptiometry (DEXA) was performed in a subgroup of
      15 patients. RESULTS: The mean daily calcium intake from food and supplementation
      was 970+/-500 mg. However, 38% of patients had an intake below the recommended
      800 mg/day. There was no significant relationship between calcium intake and age,
      gender, bone mineral density, serum calcium or albumin, type of fracture or body
      mass index. The mean free plasma calcium concentration was 2.3+/-0.1, i.e. within
      the reference limit. In 2005, 80% of the patients who underwent DEXA had manifest
      osteoporosis. There was a trend towards decreased calcium intake over the
      observation period, with a mean calcium intake below 800 mg/day in 2005.
      CONCLUSIONS: Hip fracture patients had a mean calcium intake above the
      recommended daily intake, as assessed by a FFQ. However, more than one-third of
      patients had an intake below the recommended 800 mg/day. The intake appeared to
      decrease over the investigated years. The relationship between calcium intake and
      fracture susceptibility is complex.

PMID- 19109660
TI  - A simple visual model to compare existing nutrient profiling schemes.
AB  - Nutrient profiling is a highly pressing issue. However, as there are currently
      various nutrient profiling schemes it may be difficult to maintain an overview.
      We therefore developed a simple visual model where the various choices that can
      be made are indicated. This allows for easy comparison of existing schemes. The
      model is available in PowerPoint format and attached as a separate file to this
      paper (see Supplementary files under Reading Tools online).

PMID- 19109659
TI  - Ruminant and industrially produced trans fatty acids: health aspects.
AB  - Fatty acids of trans configuration in our food come from two different sources -
      industrially produced partially hydrogenated fat (IP-TFA) used in frying oils,
      margarines, spreads, and in bakery products, and ruminant fat in dairy and meat
      products (RP-TFA). The first source may contain up to 60% of the fatty acids in
      trans form compared to the content in ruminant fat which generally does not
      exceed 6%. In Western Europe, including Scandinavia, the average daily intake of
      IP-TFA has decreased during the recent decade due to societal pressure and a
      legislative ban, whereas the intake of RP-TFA has remained stable.In spite of
      this decrease we have found that in many countries consumption >20 g of IP-TFA in
      a one-meal menu consisting of some popular foods is possible, even though the
      average intake of IP-TFA in these countries is low. Subgroups of the populations
      may therefore, on average, consume >5 g IP-TFA per day. This level of consumption
      is generally not possible for RP-TFA. A daily intake of 5 g TFA (primarily IP
      TFA) is associated with a 29% increased risk of coronary heart disease. Such an
      association is not found for RP-TFA up to a daily intake of 4 g.The high amount
      of IP-TFA in popular foods, the evidence of a more harmful effect on health by IP
      TFA than by RP-TFA, and the feasibility of eliminating IP-TFA from foods without
      side effects for the population, suggest that a selective elimination of IP-TFA
      from our food is a 'low hanging fruit' in the quest for a more healthy diet for
      subgroups of the population.

PMID- 19109661
TI  - Absorption, excretion, and retention of selenium from a high selenium yeast in
      men with a high intake of selenium.
AB  - OBJECTIVE: The purpose of this study was to evaluate the pharmacokinetics of a
      single dose of Selenium (Se) from yeast given to humans with a habitual long-term
      daily intake at a supra-nutritional level. METHODS: Twelve healthy males with a
      daily supplemental intake of 300 microg Se as selenised yeast over 10 weeks were
      supplemented with a single dose of 327 microg as stable (77)Se incorporated into
      selenised yeast manufactured by the same standardised process (SelenoPrecise(R),
      Pharma Nord, Denmark). RESULTS: Absorption of Se from (77)Se-enriched yeast was
      89+/-4% and the retention was 74+/-6%. The (77)Se excretion from the single-dose
      was 47+/-15 microg in urine and 37+/-13 microg in faeces. The maximum, enriched
      (77)Se concentration in plasma was 9.8+/-1.5 microg/l and the time to maximum was
      9.2 hours. The plasma halftime of (77)Se was longer with increasing time; 1.7
      days for the initial phase ((1/2)-2 days), 3.0 days for the middle phase (2-3
      days) and 11.1 days for the later phase (3-14 days). CONCLUSION: The Se from the
      standardised Se-enriched yeast was well absorbed and retained in the body.

PMID- 19109662
TI  - Effect of peptides derived from food proteins on blood pressure: a meta-analysis
      of randomized controlled trials.
AB  - BACKGROUND: In clinical trials, peptides derived from food proteins have shown an
      effect on blood pressure. This biological mechanism is mainly due to inhibition
      of angiotensin-I-converting enzyme (ACE), thereby regulating blood pressure
      through the renin-angiotensin system. A meta-analysis of these trials is needed
      to better quantify their effect, sources of variation, and possible publication
      bias. OBJECTIVE: To perform a meta-analysis of placebo-controlled clinical trials
      on peptides derived from food proteins and their effect on blood pressure.
      DESIGN: Trials identified using a defined search strategy in PubMed were included
      in the meta-analysis, and their pooled effect was estimated with a random effects
      model. RESULTS: Pooled effect of peptides was -5.13 mmHg (95% CI: -7.12, -3.14)
      for systolic blood pressure, and -2.42 mmHg (95% CI: -3.82, -1.03) for diastolic
      blood pressure. There were indications of publication bias for diastolic blood
      pressure data. CONCLUSIONS: Peptides derived from food proteins may lead to
      significantly reduced blood pressure and could therefore be a supplement or
      alternative to pharmaceutical treatment for mild hypertension. Their effect seems
      more pronounced, or at least comparable, to that of other food components studied
      by randomized controlled trials. A high proportion of the reported trials was
      carried out using the well-known ACE inhibiting tripeptides - Valine-Proline
      Proline (VPP) and Isoleucine-Proline-Proline (IPP).

PMID- 19109663
TI  - Targeted delivery of activatable fluorescent pro-apoptotic peptide into live
      cells.
AB  - A new fluorescence imaging system is used to visualize the specific cytotoxic
      biomolecule delivery within living biological samples by means of FRET quenching.

PMID- 19109664
TI  - Interactions and reactions in some 2,2'-disubstituted biphenyls--an open or shut
      case.
AB  - 2-Dimethylaminobiphenyls bearing an electron deficient alkene in the 2' position
      show either Me2N...C=C interactions (2.941-2.976 A) or form a new N-C bond (1.586
      1.604 A) to give a zwitterion. The former provides a model for an intermolecular
      interaction, while the latter provides structural information on organic anionic
      systems uncoordinated by metal cations.

PMID- 19109665
TI  - Asymmetric reduction of ketimines with trichlorosilane employing an imidazole
      derived organocatalyst.
AB  - Organocatalysts for the asymmetric reduction of ketimines are presented that
      function well at low catalyst loadings providing chiral amines in good yield and
      enantioselectivity, the latter appearing to be independent of the ketimine
      substrate geometry.

PMID- 19109666
TI  - Studies toward the analysis of S-nitrosoproteins.
AB  - An immuno-spin trapping method for the analysis of S-nitrosoproteins based on the
      reaction of protein thiyl radicals with 5,5-dimethyl-1-pyrroline N-oxide has been
      developed.

PMID- 19109667
TI  - Synthesis of unsymmetrical ketones via simple C-H activation of aldehydes and
      concomitant hydroacylation of vinyl sulfonates.
AB  - A new and simple protocol for the direct functionalisation of aldehydes with
      concomitant conversion into ketones via C-C bond formation has been developed.
      The reaction effectively enables the direct C-H activation of an aldehyde by
      mixing of an aldehyde and a vinyl sulfonate under aerobic conditions or using
      hydrogen peroxide as a sub-stoichiometric reagent.

PMID- 19109668
TI  - Synthesis of the originally proposed structures of elatenyne and an enyne from
      Laurencia majuscula.
AB  - A bidirectional synthesis of the originally proposed structures for the natural
      products elatenyne and a chloroenyne from Laurencia majuscula is described along
      with a reassessment of the structures of the halogenated enynes based upon a 13C
      NMR chemical shift/structure correlation.

PMID- 19109669
TI  - A novel intramolecular Ugi reaction with 7-azabicyclo[2.2.1]heptane derivatives
      followed by post-condensation acylations: a new entry to azanorbornyl
      peptidomimetics.
AB  - beta-amino acids have been employed in the past as bifunctional building blocks
      in intramolecular Ugi multicomponent reactions to yield beta-lactam derivatives.
      By using 7-azabicyclo[2.2.1]heptane-2-carboxylic acid, a different outcome has
      been observed and rationalised. The final compounds are polyfunctionalised
      azabicyclic peptidomimetics, and further elaboration can be achieved exploiting
      an additional carboxylic group that is not involved in the multicomponent step.

PMID- 19109671
TI  - Novel dansyl-appended calix[4]arene frameworks: fluorescence properties and
      mercury sensing.
AB  - Covalently-attached fluorophores may impart enhanced chemosensing capabilities to
      calixarene frameworks. Synthesis and characterization of six novel dansyl
      appended calix[4]arenes, namely, H/Dan4, NO2/Dan4, H/(OH)2Dan2, H/(Ester)2(Dan)2,
      t-Bu/(OH)2Dan2, and t-Bu/(Ester)2Dan2, containing two or four dansyl moieties are
      reported. Among these, fluorescence intensity of NO2/Dan4 is observed to decrease
      significantly in the presence Hg2+ in the solution. Based on the decrease in
      fluorescence, a limit of detection for Hg2+ of 20 ppb is obtained. NO2/Dan4 as a
      chemosensing agent for Hg2+ shows excellent selectivity and adequate
      reversibility. Complexation of NO2/Dan4 with Hg2+ is investigated using
      fluorescence spectroscopy and is observed to be 2:1. The formation constant of
      (NO2/Dan4)2Hg2+ is estimated to be 5.2(+/- 0.8) x 10(10) M(-2) at ambient
      conditions. These observations are traced to the fact that while all other dansyl
      appended calix[4]arenes show cone conformation in the solution, NO2/Dan4 is in
      the 1,3-alternate conformation. Stokes shift versus solvent orientational
      polarizability for NO2/Dan4 also indicates the difference in the ground- to
      excited-state dipole moment of this compound to be the maximum among all six,
      rendering it most sensitive to its environment. Fluorescence emission of NO2/Dan4
      in nonpolar chloroform, polar-aprotic acetonitrile, and polar-protic ethanol is
      observed to be different than that of the rest of the dansyl-appended compounds
      as well.

PMID- 19109670
TI  - Solid-phase synthesis of cyclic peptide chitinase inhibitors: SAR of the argifin
      scaffold.
AB  - A new, highly efficient, all-solid-phase synthesis of argifin, a natural product
      cyclic pentapeptide chitinase inhibitor, is reported. The synthesis features
      attachment of an orthogonally protected Asp residue to the solid support and
      assembly of the linear peptide chain by Fmoc SPPS prior to cyclisation and side
      chain manipulation on-resin. Introduction of the key N-methyl carbamoyl
      substituted Arg side chain is achieved via derivatisation of a selectively
      protected Orn residue, prior to cleavage from the resin and side-chain
      deprotection. A severe aspartimide side-reaction observed upon final deprotection
      is circumvented by the use of a novel aqueous acidolysis procedure. The
      flexibility of the synthesis is demonstrated by the preparation of a series of
      argifin analogues designed from the X-ray structure of the natural product in
      complex with a representative family 18 chitinase.

PMID- 19109672
TI  - Conformational analysis of the neutral exopolysaccharide produced by
      Lactobacillus delbrueckii ssp. bulgaricus LBB.B26.
AB  - The conformational properties of the neutral exopolysaccharide produced by
      Lactobacillus delbrueckii ssp. bulgaricus LBB.B26 have been studied by NMR
      measurements and molecular modelling. The exopolysaccharide, with an average
      molecular mass of 1.3 x 10(6) Da, was previously determined to consist of
      pentasaccharide repeating units with the following structure: -->3)-beta-D-Galp
      (1-->4)-beta-D-Glcp-(1-->3)-beta-d-Galf-(1-->3)-[alpha-D-Glcp-(1-->6)-]alpha-D
      Galp-(1-->. Adiabatic maps were generated for each of the disaccharide fragments
      in the repeating unit. In addition, free energy maps calculated from MD
      simulations were obtained for each of the glycosidic linkages in an extended
      repeating unit and the influence of the Galf residue on the conformational
      properties of the repeating unit was investigated. The values of the global
      energy minima provided by the free energy maps were used to build a polymer
      chain. The polysaccharide was shown to have a random coil structure, without
      stable extended helical motifs.

PMID- 19109673
TI  - New theophylline-activated Diels-Alderase ribozymes by molecular engineering.
AB  - Allosteric ribozymes were developed by rational design and step-wise
      optimization. These ribozymes accelerate a Diels-Alder reaction between
      anthracene and maleimide derivatives. The optimized sequence is efficiently
      activated by theophylline under single and multiple turnover conditions and
      distinguishes between structurally similar effector molecules.

PMID- 19109674
TI  - Crown-ether- and porphyrin-attached gel-phase resins in thermodynamically
      controlled rotaxane assembly.
AB  - Results of gel-phase proton high resolution magic angle spinning (HR MAS) NMR
      spectroscopy are described for a systematic study of the reversible,
      thermodynamically-controlled assembly of surface-attached neutral rotaxanes and
      pseudorotaxanes based on a three-component system consisting of a naphthodiimide
      thread unit, a naphthalene crown shuttle, and metalloporphyrin stoppers. Further
      to the previous systems based on an immobilised thread unit, we report here on
      the alternative systems where firstly a crown shuttle unit, and secondly
      metalloporphyrin stopper units, are attached to polystyrene beads, with the other
      two rotaxane components supplied in the surrounding solution phases in each case.
      Variations in concentration, temperature, and the effects of the addition of
      alkali metal salts are investigated. Within some limitations imposed by the
      technique itself, these results confirm that for each of the single entities
      attached in turn to polystyrene beads, rotaxane formation parallels that observed
      in the analogous solution-phase systems.

PMID- 19109675
TI  - Biocatalytical production of (5S)-hydroxy-2-hexanone.
AB  - Biocatalytical approaches have been investigated in order to improve
      accessibility of the bifunctional chiral building block (5S)-hydroxy-2-hexanone
      ((S)-2). As a result, a new synthetic route starting from 2,5-hexanedione (1) was
      developed for (S)-2, which is produced with high enantioselectivity (ee >99%).
      Since (S)-2 can be reduced further to furnish (2S,5S)-hexanediol ((2S,5S)-3),
      chemoselectivity is a major issue. Among the tested biocatalysts the whole-cell
      system S. cerevisiae L13 surpasses the bacterial dehydrogenase ADH-T in terms of
      chemoselectivity. The use of whole-cells of S. cerevisiae L13 affords (S)-2 from
      prochiral 1 with 85% yield, which is 21% more than the value obtained with ADH-T.
      This is due to the different reaction rates of monoreduction (1-->2) and
      consecutive reduction (2-->3) of the respective biocatalysts. In order to
      optimise the performance of the whole-cell-bioreduction 1 2 with S. cerevisiae,
      the system was studied in detail, revealing interactions between cell-physiology
      and xenobiotic substrate and by-products, respectively. This study compares the
      whole-cell biocatalytic route with the enzymatic route to enantiopure (S)-2 and
      investigates factors determining performance and outcome of the bioreductions.

PMID- 19109676
TI  - Synthesis of (-)-pericosine B, the antipode of the cytotoxic marine natural
      product.
AB  - The stereoselective synthesis of (-)-pericosine B, which is the antipode of the
      cytotoxic metabolite of the fungus Periconia byssoides OUPS-N133 separated from
      the sea hare, was accomplished in 9 steps in 12% total yield from (-)-quinic
      acid, together with the synthesis of its epimer. Every crucial step of this total
      synthesis, including ring opening of a beta-epoxide and NaBH4 reduction of an
      unstable beta,gamma-unsaturated enone, proceeded with excellent
      stereoselectivity.

PMID- 19109677
TI  - Synthesis and evaluation of guanidinyl pyrrolidines as bifunctional catalysts for
      enantioselective conjugate additions to cyclic enones.
AB  - Guanidinyl pyrrolidines derived from 'S'-proline are effective catalysts for the
      enantioselective conjugate addition of malonate, nitroalkane and other carbon and
      heteroatom nucleophiles to cyclohexenone and cyclopentenone in the absence of
      basic additives. The stereoselectivity is strongly dependent on catalyst loading
      as well as reaction concentration.

PMID- 19109678
TI  - Formylnitroenamines: useful building blocks for nitrated pyridones and
      aminopyridines with functional groups.
AB  - beta-formyl-beta-nitroenamines possess both an electrophilic formyl group and a
      nucleophilic amino group and, therefore, serve as C3N1 building blocks having a
      nitro group to afford nitropyridones and aminonitropyridines with a functional
      group at the 3-position. Upon treatment with malonic acid derivatives or beta
      keto esters, nitropyridones were obtained, whereas reactions with functionalized
      acetonitriles afford aminonitropyridines, via a formal transfer of an alkyl group
      from the ring nitrogen to the imino group. These procedures provide practical and
      useful methods for preparation of heterocycles with a nitro group.

PMID- 19109679
TI  - Lithiation-electrophilic trapping of N-sulfonyl-activated ethylene aziridines.
AB  - A detailed study on the lithiation-electrophilic trapping of N-sulfonyl ethylene
      aziridines is described. The optimum results required use of a N-2,4,6-tri-iso
      propylbenzenesulfonyl activating group and lithiation using 3 equiv. of s-BuLi
      PMDETA for 1 minute before addition of the electrophile. In situ trapping with
      Me3SiCl was also successful. Electrophilic trapping with aldehydes provided a
      stereoselective route to syn-hydroxy aziridines. Alternatively, keto aziridines
      could be stereoselectively reduced to syn-hydroxy aziridines using NaBH4-CeCl3.
      The relative stereochemistry in two of the hydroxy aziridines was established
      unequivocally by X-ray crystallography.

PMID- 19109680
TI  - Asymmetric esterification of ketenes catalyzed by an N-heterocyclic carbene.
AB  - The chiral N-heterocyclic carbene precursor, derived from L-pyroglutamic acid,
      was found to be an efficient precatalyst for the enantioselective esterification
      of alkylarylketenes with benzhydrol to give the corresponding esters in good
      yields with good to high enantioselectivities (up to 95% ee).

PMID- 19109681
TI  - Direct electrochemical alpha-cyanation of N-protected cyclic amines.
AB  - alpha-cyanation of N-protected cyclic amines was achieved using a direct
      electrochemical method. Unsubstituted N-protected cyclic amines were easily
      cyanated at the alpha-position using an undivided cell in high yields; moreover,
      alpha-cyanation of alpha'-substituted pyrrolidine and alpha'-,beta'- or gamma
      substituted piperidines smoothly proceeded in high yield and with high to
      excellent diastereoselectivity. alpha-Substituted N-cyano-pyrrolidines and 
      piperidines were also cyanated at the more substituted position (the alpha
      position) using a divided cell with high yield and high regioselectivity.

PMID- 19109682
TI  - Multivalent iminosugars to modulate affinity and selectivity for glycosidases.
AB  - A series of mono-, di- and tri-valent iminosugars based on oligoethylene
      scaffolds and N-substituted deoxynojirymicin epitopes have been synthesized by
      "click chemistry" to study the effect of multivalency on glycosidase inhibition.
      Biological evaluation evidenced differences in the inhibition trends as a
      function of the enzyme nature. The results demonstrate that multivalency can be
      used in some case to modulate both the affinity and the selectivity of
      glycosidase inhibition.

PMID- 19109683
TI  - A novel organogelator incorporating tert-butyl esters of asparagines.
AB  - A novel organogelator based on tert-butyl esters of asparagines has been
      synthesized and its organogelation abilities have been investigated. The
      rheological characterization has confirmed the gelation behavior, and its
      thixotropic properties. Furthermore, the morphological studies performed reveal a
      spherical structure. Thus, this organogelator can be considered as a new example
      of the emerging, but still reduced, list of gels with a non-fibrillar assembly.

PMID- 19109684
TI  - New cyclodextrin dimers and trimers capable of forming supramolecular adducts
      with shape-specific ligands.
AB  - Bridged cyclodextrin dimers and trimers, in which respectively two and three
      hydrophobic cavities lie in close proximity, display much higher binding
      affinities and molecular selectivities than do parent cyclodextrins (CDs). By
      joining betaCD units with links inserted at different positions (2-2', 3-2', 6-2'
      or 6-2'-6'') and interposing spacers of different lengths and shapes, multicavity
      structures can be synthesized that are precisely tailored to fit specific guest
      molecules. This enzyme-mimicking strategy can also be used to generate stable
      supramolecular adducts. A series of CD dimers and trimers was prepared in good
      yields by carrying out the critical synthetic steps under power ultrasound (US)
      or microwave (MW) irradiation. Starting from azide and acetylenic CD derivatives,
      we exploited an efficient MW-promoted Huisgen 1,3-dipolar cycloaddition in the
      presence of Cu(I) salts. The resulting bridged CD derivatives gave stable adducts
      with magnetic-resonance-imaging contrast agents (MRI CAs) containing
      gadolinium(III) chelates. These inclusion complexes were found to be 2 to 3
      orders of magnitude more stable than those formed by betaCD and to be endowed
      with high relaxivity values.

PMID- 19109685
TI  - A facile and general method for the synthesis of 6,12-diaryl-5,11
      dihydroindolo[3,2-b]carbazoles.
AB  - A facile and general two-step method towards 6,12-diaryl-5,11-dihydroindolo[3,2
      b]carbazoles has been developed. Hydroiodic acid was an efficient catalyst for
      the condensation of indole and aromatic aldehydes, and iodine was used as an
      oxidation reagent to afford symmetrical 6,12-diaryl-5,11-dihydroindolo[3,2
      b]carbazoles in moderate to good overall yields.

PMID- 19109686
TI  - Development and application of a novel acridinium ester for use as a
      chemiluminescent emitter in nucleic acid hybridisation assays using
      chemiluminescence quenching.
AB  - Chemiluminescent acridinium esters (AEs) permit the development of high
      sensitivity ligand binding assays due to a combination of high intensity light
      emission and very low backgrounds. Here these advantages are exploited for use in
      homogeneous nucleic acid hybridisation assays using quenched chemiluminescence.
      AE chemiluminescence is conventionally initiated at highly alkaline pH. Novel
      "active" AEs were designed that permit initiation under conditions compatible
      with maintenance of nucleic acid hybrids (i.e. pH less than 9). Methyl red was
      found to be a dark quencher species capable of functioning at this pH. Practical
      application of the chemiluminescence quenching assay system has been demonstrated
      using two model nucleic acid hybridisation assays based on intra- and
      intermolecular emitter/quencher pairs.

PMID- 19109687
TI  - Rapid screening and scale-up of transaminase catalysed reactions.
AB  - A rapid, high-throughput screening methodology has been developed for the
      determination of transaminase activity. This pH based, colorimetric assay can
      also be used to scale reactions directly from 100 microL screening scale to 25 mL
      development scale. Additionally, three techniques have been developed to drive
      transamination reactions toward complete conversion. The first method uses
      lactate dehydrogenase to remove the inhibitory pyruvate keto acid by-product from
      the reaction and drive reaction equilibrium toward the desired amine. The second
      method is a single enzyme system, and uses a large excess of isopropylamine to
      drive the transamination. Method three requires only a catalytic amount of amine
      donor, as an amino acid dehydrogenase is employed to regenerate the amine donor
      in situ using ammonia. All three systems have been demonstrated for the
      production of optically pure methylbenzylamine from acetophenone. An enantiomeric
      excess of >99% was achieved for both the R- and S-methylbenzylamine products.

PMID- 19109690
TI  - Characterization of a member of a new Potyvirus species infecting arracacha in
      Brazil.
AB  - An arracacha (Arracacia xanthorrhiza) plant collected in Brazil was found to be
      infected by a new virus. This viral isolate (named C17) systemically infected
      Nicotiana benthamiana and Apium graveolens. A polyclonal antibody was raised, and
      analysis of our arracacha germplasm collection showed a high infection rate of
      C17-like viruses (93% infection). Sequencing of the ca. 1.7 kb 3'-terminal
      genomic region revealed a typical potyvirus genome organization. It shared less
      than 70% nucleotide identity with any other potyvirus sequence, which thus
      indicated that it is possibly a member of a new Potyvirus species tentatively
      named Arracacha mottle virus (AMoV).

PMID- 19109691
TI  - Differential microbial communities in hot spring mats from Western Thailand.
AB  - The microbial communities of freshwater hot spring mats from Boekleung (Western
      Thailand) were studied. Temperatures ranged from over 50 up to 57 degrees C.
      Green-, red-, and yellow colored mat layers were analyzed. In order to detect the
      major components of the microbial communities constituting the mat as well as the
      microorganisms showing significant metabolic activity, samples were analyzed
      using DNA- and RNA-based molecular techniques, respectively. Microbial community
      fingerprints, performed by denaturing gradient gel electrophoresis (DGGE),
      revealed clear differences among mat layers. Thermophilic phototrophic
      microorganisms, Cyanobacteria and Chloroflexi, constituted the major groups in
      these communities (on average 65 and 51% from DNA and RNA analyses,
      respectively). Other bacteria detected in the mat were Bacteroidetes, members of
      the Candidate Division OP10, Actinobacteria, and Planctomycetes. Differently
      colored mat layers showed characteristic bacterial communities and the major
      components of the metabolically active fraction of these communities have been
      identified.

PMID- 19109692
TI  - Membrane fusion between liposomes containing SNARE proteins involved in mast cell
      exocytosis.
AB  - OBJECTIVE AND DESIGN: We monitored the membrane fusion of liposomes to determine
      if the minimal components of soluble N-ethyl maleimide-sensitive factor
      attachment protein receptor (SNARE), which is involved in mast cell exocytosis,
      have fusogenic activity. METHODS: Three core components of SNARE were
      reconstituted into liposomes. Membrane fusion between liposomes containing
      vesicle associated membrane protein (VAMP) -7 or -8 and liposomes containing
      synaptosomal-associated protein 23 kDa (SNAP23) and syntaxin-3 or -4 was
      monitored by fluorescence resonance energy transfer. RESULTS: The combination of
      SNAP23/syntaxin-3/VAMP-8 showed the most efficient liposome-liposome fusogenic
      activity. Liposomes with VAMP-7 exhibited poor fusogenic activity regardless of
      the syntaxin isoform. CONCLUSION: The core components of SNAP23, syntaxin-3, and
      VAMP-8 appear to be minimal machinery to induce membrane fusion, while VAMP-7
      appears to be unessential for membrane fusion.

PMID- 19109693
TI  - Serum of patients with septic shock stimulates the expression of Trem-1 on U937
      monocytes.
AB  - OBJECTIVES: To describe the concentrations of sTREM-1 in patients with sepsis and
      to explore the effects of their serum on the expression of TREM-1 on U937
      monocytes. METHODS: Blood was sampled at regular time intervals in 56 patients
      with sepsis. Concentrations of tumour necrosis factor-alpha (TNFalpha),
      interleukin-1beta (IL-1alpha), IL-6, IL-8, IL-10 and IL-12p70 and sTREM-1 were
      measured. U937 monocytes were incubated in the presence of serum at sepsis onset.
      RESULTS: Median sTREM-1 concentration on day 1 for patients with septic shock was
      915 pg/ml and 228.5 pg/ml for those without shock (p = 0.002). TNFalpha, IL
      1alpha, IL-6, IL-8 and IL-10 did not differ between them. A positive correlation
      was found between changes of sTREM-1 and SOFA scores from day 1 to 7. Sera of
      patients with septic shock evoked a significant increase of the expression of
      TREM-1. The concentrations of TNFalpha and IL-8 in supernatants increased only
      after stimulating with sera of patients without shock, but not after stimulating
      with sera of patients with shock. CONCLUSIONS: Levels of sTREM-1 correlated with
      sepsis severity. sTREM-1 is considerably higher in patients with shock compared
      to patients without shock. The serum of shocked patients could stimulate the
      expression of TREM-1 on U937 monocytes.

PMID- 19109694
TI  - Inflammation symptoms and signalling.

PMID- 19109695
TI  - Mitochondrial DNA variation in the caramote prawn Penaeus (Melicertus) kerathurus
      across a transition zone in the Mediterranean Sea.
AB  - In this study we analysed mitochondrial DNA variation in Penaeus kerathurus
      prawns collected from seven locations along a transect across the Siculo-Tunisian
      region in order to verify if any population structuring exists over a limited
      geographical scale and to delineate the putative transition zone with sufficient
      accuracy. Partial DNA sequences of COI and 16S genes were analysed. In contrast
      to the highly conservative 16S gene, the COI sequences exhibited sufficient
      diversity for population analysis. The COI gene revealed low levels of haplotype
      and nucleotide diversities. The size of the annual landings of this commercial
      species suggests large population sizes. Hence, the low genetic diversity
      detected in this study could indicate a possible reduction in effective
      population sizes in the past. We detected significant genetic differentiation
      between eastern and western populations likely due to restricted gene flow across
      the Siculo-Tunisian boundary. We discuss the different evolutionary forces that
      may have shaped the genetic variation and suggest that the genetic divide is
      probably maintained by present-day dispersal limitation.

PMID- 19109696
TI  - IL-1beta caused pancreatic beta-cells apoptosis is mediated in part by
      endoplasmic reticulum stress via the induction of endoplasmic reticulum Ca2+
      release through the c-Jun N-terminal kinase pathway.
AB  - Endoplasmic reticulum (ER) homeostasis is crucial for beta-cell function and
      survival. Direct as well as indirect evidence has pointed toward Ca(2+) as an
      important determinant of interleukin-1beta (IL-1beta)-induced beta-cell
      dysfunction and apoptosis. In the present study, we show that IL-1beta-induced
      apoptosis and necrosis in primary rat beta-cells and MIN6 cells largely depends
      on ER stress, ER Ca(2+) release, and c-Jun N-terminal kinase (JNK) activation.
      beta-cells also showed marked sensitivity to apoptosis induced by
      sarcoendoplasmic reticulum Ca(2+) ATPase (SERCA) blockers, thapsigargin and
      cyclopiazonic acid (CPA). IL-1beta induced ER Ca(2+) release, which was
      paralleled by an IL-1beta-dependent induction of JNK activation and the ER stress
      response, including activation of PRK (RNA-dependent protein kinase)-like ER
      kinase (PERK). Furthermore, reduced activation of JNK, utilizing JNK inhibitor
      SP600125, resulted in significant protection from IL-1beta- or thapsigargin
      induced apoptosis via ER stress. In conclusion, our results suggest that the IL
      1beta-induced depletion of ER Ca(2+) and activation of the ER stress via JNK
      pathway are potential contributory mechanisms to beta-cell death.

PMID- 19109699
TI  - Dictyostelium development: a prototypic Wnt pathway?
AB  - Although Wnt signaling is ubiquitous within the animal phylogenetic group, it is
      unclear how it evolved. Genes related to the components of Wnt pathway are found
      in other eukaryotes and one of the most studied of these non-metazoan organisms
      is the social amoeba Dictyostelium discoideum. This organism contains the enzyme
      GSK-3 and a beta -catenin homolog, Aardvark (Aar). Both are required to regulate
      pattern formation during multi-cellular stages of Dictyostelium development. Aar
      is also required for formation of adherens junctions, as seen in animals.
      Finally, analysis of the completed Dictyostelium genome shows there to be 16
      Frizzled (Fz) gene homologs. This chapter discusses Dictyostelium development and
      the role of these proteins.

PMID- 19109698
TI  - Evolution of the Wnt pathways.
AB  - Wnt proteins mediate the transduction of at least three major signaling pathways
      that play central roles in many early and late developmental decisions. They
      control diverse cellular behaviors, such as cell fate decisions, proliferation,
      and migration, and are involved in many important embryological events, including
      axis specification, gastrulation, and limb, heart, or neural development. The
      three major Wnt pathways are activated by ligands, the Wnts, which clearly belong
      to the same gene family. However, their signal is then mediated by three separate
      sets of extracellular, cytoplasmic, and nuclear components that are pathway
      specific and that distinguish each of them. Homologs of the Wnt genes and of the
      Wnt pathways components have been discovered in many eukaryotic model systems and
      functional investigations have been carried out for most of them. This review
      extracts available data on the Wnt pathways, from the protist Dictyostelium
      discoideum to humans, and provides from an evolutionary prospective the overall
      molecular and functional conservation of the three Wnt pathways and their
      activators throughout the eukaryotic superkingdom.

PMID- 19109700
TI  - Monitoring patterns of gene expression in Dictyostelium by beta-galacotsidase
      staining.
AB  - Monitoring the spatial distribution of prespore and pstB cell types is a
      sensitive method to monitor GSK-3 and Aar activity during Dictyostelium
      development. Cell-specific expression of lacZ marker genes can be readily
      detected using enzymatic cleavage of the substrate X-gal. This protocol describes
      a simple method for beta-galactosidase staining in developed Dictyostelium
      structures.

PMID- 19109701
TI  - Use of the Dictyostelium stalk cell assay to monitor GSK-3 regulation.
AB  - GSK-3 activity mediates cAMP repression of stalk induction of cells in low
      density monolayer culture. The lower the GSK-3 activity the greater the
      percentage of stalk cells formed. This protocol describes a robust and
      quantitative method utilizing an adapted stalk cell monolayer assay to measure
      GSK-3 activation.

PMID- 19109702
TI  - Wnt signaling in cnidarians.
AB  - Cnidarians are an ancient group of animals at the base of metazoan evolution.
      They exhibit a simple body plan with only one well-defined body axis and a small
      number of cell types. Cnidarians are also well known for their enormous
      regeneration capacity. Recent work in the freshwater polyp Hydra and in the sea
      anemone Nematostella has identified an unexpectedly high level of genetic
      complexity of wnt genes. Canonical Wnt signaling acts in pattern formation and
      regeneration of Hydra and also in gastrulation and early embryogenesis of
      Nematostella. Vertebrate-specific Wnt-antagonists were also identified from
      cnidarians and exhibit similar conserved functions. The simple cnidarian body
      plan and the now available genomes from Hydra and Nematostella, together with new
      functional approaches, make these animals an attractive model for studying the
      basic functions of canonical and non-canonical Wnt signaling.

PMID- 19109703
TI  - Detecting expression patterns of Wnt pathway components in Nematostella vectensis
      embryos.
AB  - The anthozoan cnidarian Nematostella vectensis has emerged as a key model system
      for evolutionary developmental biology studies, and this animal' usefulness will
      grow with the recent sequencing of its genome. In particular, work done in
      Nematostella is providing insight into the role of the Wnt pathway in the
      evolution of pattern formation. This chapter describes methods to maintain and
      spawn these animals, and detailed protocols to detect expression patterns of Wnt
      pathway components in Nematostella eggs and embryos.

PMID- 19109704
TI  - Detection of expression patterns in Hydra pattern formation.
AB  - Cnidarians are simple metazoans with only two body layers and a primitive nervous
      system. They are famous for their nearly indefinite regeneration capacity. Recent
      work has identified most of the Wnt subfamilies and Wnt antagonists known from
      vertebrates in this basal animal model. Wnt signaling and BMP signaling have been
      shown to act in Hydra pattern formation and regeneration. Because recent genomic
      work in Hydra and Nematostella revealed many genes for vertebrate signaling
      pathways and transcription factors to be present in this more than 500 Myr-year
      old phylum, future work will focus on the function and expression of these genes
      in Hydra pattern formation and regeneration. This chapter presents an in situ
      hybridization protocol, which is largely based on a lab protocol of the Bode lab
      that has proven to be extremely useful in the characterization of many
      developmental genes from Hydra.

PMID- 19109705
TI  - Analysis of Wnt signaling during Caenorhabditis elegans postembryonic
      development.
AB  - Wnts play a central role in the development of many cells and tissue types in all
      species studied to date. Like many other extracellular signaling pathways,
      secreted Wnt proteins are involved in many different processes; in C. elegans
      these include: cell proliferation, differentiation, cell migration, control of
      cell polarity, axon outgrowth and control of the stem cell niche. Perturbations
      in Wnt signaling are also key factors in cancer formation, and therefore of
      interest to oncobiologists. Wnts are secreted glycoproteins, which bind to
      Frizzled transmembrane receptors and signal either through, or independently of
      beta-catenin. Both beta-catenin-dependant (Wnt/beta-catenin) and -independent
      pathways function during postembryonic development in C. elegans and allow Wnt
      researchers to explore aspects of Wnt signaling both in common with other
      organisms and unique to the nematode. Chapter 9 in Volume 2 discusses various
      processes controlled by Wnt signaling during C. elegans embryonic development;
      this chapter discusses Wnt controlled processes that occur during postembryonic
      development, including an overview of methods used to observe their function.

PMID- 19109707
TI  - Function of the wingless signaling pathway in Drosophila.
AB  - Signaling by the wingless pathway has been shown to govern numerous developmental
      processes. Much of our current understanding of wingless signaling mechanisms
      comes from studies conducted in Drosophila melanogaster, which offers superior
      experimental tractability for genetic and developmental studies. Wingless
      signaling is highly consequential during normal development and patterning of
      Drosophila. Its earliest identifiable role during development of Drosophila is in
      the embryonic segmentation cascade, wherein wingless functions as a segment
      polarity gene and serves to pattern each individual segment along the antero
      posterior axis of the developing embryo. Subsequent developmental roles fulfilled
      by wingless include patterning the developing wings, legs, eyes, CNS, heart, and
      muscles. Each of these developmental contexts offers excellent systems to query
      mechanisms regulating different aspects of wingless signal transduction such as
      synthesis, secretion, reception, and transcription. This chapter presents a brief
      overview on the functions of wingless signaling during development of Drosophila
      melanogaster.

PMID- 19109706
TI  - Wnt signaling during Caenorhabditis elegans embryonic development.
AB  - Wnt signaling has been demonstrated to regulate diverse cell processes throughout
      the development of the Caenorhabditis elegans embryo. This chapter describes
      methods that have been used to investigate some of these Wnt-dependent processes:
      endoderm specification, mitotic spindle orientation, and cell migration.

PMID- 19109708
TI  - Visualization of PCP defects in the eye and wing of Drosophila melanogaster.
AB  - "Tissue" or "planar" polarity is a characteristic of many epithelial tissues and
      is not only required for proper cell alignment, but in many instances is
      absolutely essential for normal function. Planar cell polarity (PCP) is the
      polarization of cells within the plane of an epithelium in a direction
      perpendicular to the axis of the apico-basal polarity. The oriented hair
      alignment in mammalian skin (feather in birds or scales in fish) and highly
      organized stereocilia bundles in the vertebrate inner ear are examples of such
      tissue organization. PCP was first described in Drosophila, with non-canonical
      Wnt signaling (also called PCP signaling, see Chapter 10, Volume 1) shown to be
      critical for its establishment. Two of the best characterized PCP models in
      Drosophila are the developing wing and the eye, where the graded activity of the
      Frizzled (Fz) receptor determines proximo-distal orientation of the wing hairs
      and mirror-imaged patterning of ommatidia, respectively. In this chapter, we
      describe simple methods to visualize PCP defects in the Drosophila eye and wing,
      in both developing and adult tissues. These methods include confocal
      immunofluorescent analysis of larval or pupal tissues, stained with antibodies
      specific to PCP components or cytoskeleton markers, and light microscopy of the
      adult eye and wing.

PMID- 19109710
TI  - High-throughput RNAi screen in Drosophila.
AB  - Genetic and biochemical analyses in model systems such as the fruitfly,
      Drosophila melanogaster, have successfully identified several genes that play key
      regulatory roles in fundamental cellular and developmental processes. However,
      the analyses of the complete genome sequences of Drosophila, as well as of
      humans, now reveal that traditional methods have ascribed functions to only a
      fraction of the total predicted genes. Thus, the roles for many, as yet
      unidentified genes, in normal development and cancer remain to be discovered. The
      challenge presented by the various large-scale genome projects is how to derive
      biologically relevant information from the raw sequences. The past few years have
      witnessed a rapid growth in the development and implementation high-throughput
      screening (HTS) technologies that researchers are now using to discover "gene
      function" in an unbiased, systematic, and time-efficient manner. In fact one of
      the most promising functional genomic approach that has emerged in the past few
      years is based on RNA-interference (RNAi), in which the introduction of double
      stranded RNA (dsRNA) into cells or whole organisms has been shown to be an
      effective tool to suppress endogenous gene expression. The RNAi technology has
      made it feasible to query the function of every gene in the genome for their
      potential function in a given cell-biological process using cell-based assays.
      This chapter discusses the application, advantages, and limitations of this
      powerful technology in the identification of novel modulators of cell-signaling
      pathways as well as its future scope and utility in designing more efficient
      genome-scale screens.

PMID- 19109711
TI  - Wnt signaling in the early sea urchin embryo.
AB  - Wnt signaling regulates a remarkably diverse array of cellular and developmental
      events during animal embryogenesis and homeostasis. The crucial role that Wnt
      signaling plays in regulating axial patterning in early embryos has been
      particularly striking. Recent work has highlighted the conserved role that
      canonical Wnt signaling plays in patterning the animal-vegetal (A-V) axis in sea
      urchin and sea anemone embryos. In sea urchin embryos, the canonical Wnt
      signaling pathway is selectively turned on in vegetal cells as early as the 16
      cell stage embryo, and signaling through this pathway is required for activation
      of the endomesodermal gene regulatory network. Loss of nuclear beta-catenin
      signaling animalizes the sea urchin embryo and blocks pattern formation along the
      entire A-V axis. Nuclear entry of beta-catenin into vegetal cells is regulated
      cell autonomously by maternal information that is present at the vegetal pole of
      the unfertilized egg. Analysis of Dishevelled (Dsh) regulation along the A-V axis
      has revealed the presence of a cytoarchitectural domain at the vegetal pole of
      the unfertilized sea urchin egg. This vegetal cortical domain appears to be
      crucial for the localized activation of Dsh at the vegetal pole, but the precise
      mechanisms are unknown. The elucidation of how Dsh is selectively activated at
      the vegetal cortical domain is likely to provide important insight into how this
      enigmatic protein is regulated during canonical Wnt signaling. Additionally, this
      information will shed light on the origins of embryonic polarity during animal
      evolution. This chapter examines the roles played by the canonical Wnt signaling
      pathway in the specification and patterning of the A-V axis in the sea urchin.
      These studies have led to the identification of a novel role for canonical Wnt
      signaling in regulating protein stability, and continued studies of Wnt signaling
      in this model system are likely to reveal additional roles for this pathway in
      regulating early patterning events in embryos.

PMID- 19109709
TI  - Wingless signaling in Drosophila eye development.
AB  - The secreted morphogen Wingless (Wg) has a variety of functions throughout
      Drosophila eye development, controlling tissue specification, growth, and
      patterning. Wg plays a critical role in subdividing the eye imaginal disc into
      separate primordia that will give rise to the adult retina and the surrounding
      head capsule. During larval development, wg is expressed in the anterior lateral
      margins of the eye disc, regions that will give rise to head cuticle; Wg
      signaling promotes the head fate and prevents these marginal regions from
      initiating ectopic photoreceptor differentiation. Expression of wg at the dorsal
      margin is earlier and stronger than at the ventral margin, allowing Wg to
      contribute to specifying the dorsal domain of the eye disc. Finally, during the
      pupal stages, wg expression surrounds the entire eye and a concentric gradient of
      Wg establishes several distinct peripheral retinal cell fates. This chapter
      reviews these aspects of Wg function and describes how to generate clones of
      cells mutant for genes encoding components of the Wg signaling pathway in the eye
      disc and examine their effects on photoreceptor differentiation by
      immunohistochemistry.

PMID- 19109712
TI  - Detecting expression patterns of Wnt pathway components in sea urchin embryos.
AB  - The animal-vegetal (A-V) axis is a maternally established asymmetry that is
      present in most animal eggs, and it plays an important role in germ-layer
      segregation. Recent work has shown that the canonical Wnt signaling pathway plays
      an evolutionarily conserved role in specifying and patterning this axis. However,
      the precise mechanisms by which this pathway is activated in the early embryo to
      pattern the A-V axis are not known in most animals. The availability of the
      Strongylocentrotus purpuratus genome sequence, the ability to experimentally
      manipulate eggs and early embryos using embryological and molecular tools, and
      the superior optical clarity of sea urchin embryos makes them an important model
      for investigating the role of the canonical Wnt pathway in specifying and
      patterning the A-V axis. Here, we provide detailed protocols for determining the
      expression and localization of mRNA and proteins in early sea urchin embryos,
      which can be used in studies examining the regulation of Wnt signaling along the
      A-V axis.

PMID- 19109713
TI  - Functional analysis of Wnt signaling in the early sea urchin embryo using mRNA
      microinjection.
AB  - The Wnt pathway is a highly conserved signal transduction pathway that plays many
      critical roles in early animal development. Recent studies have shown that this
      pathway plays a conserved role in the specification and patterning of the animal
      vegetal (A-V) axis in sea urchins and sea anemones. These observations have
      suggested that the common ancestor to cnidarians and bilaterians used the Wnt
      signaling pathway for specifying and patterning this maternally established axis.
      Because the A-V axis plays a critical role in germ layer segregation, a better
      understanding of how the Wnt pathway is regulated along the A-V axis will provide
      key insight into the molecular mechanisms regulating germ layer segregation and
      germ layer evolution in animal embryos. Here, we provide a detailed protocol for
      using mRNA microinjection that can be used to analyze Wnt signaling in early sea
      urchin embryos. This protocol can also be adapted to introduce morpholino anti
      sense oligonucleotides into sea urchin embryos.

PMID- 19109714
TI  - Wnt signaling mediates diverse developmental processes in zebrafish.
AB  - A combination of forward and reverse genetic approaches in zebrafish has revealed
      novel roles for canonical Wnt and Wnt/PCP signaling during vertebrate
      development. Forward genetics in zebrafish provides an exceptionally powerful
      tool to assign roles in vertebrate developmental processes to novel genes, as
      well as elucidating novel roles played by known genes. This has indeed turned out
      to be the case for components of the canonical Wnt signaling pathway. Non
      canonical Wnt signaling in the zebrafish is also currently a topic of great
      interest, due to the identified roles of this pathway in processes requiring the
      integration of cell polarity and cell movement, such as the directed migration
      movements that drive the narrowing and lengthening (convergence and extension) of
      the embryo during early development.

PMID- 19109715
TI  - Determination of mRNA and protein expression patterns in zebrafish.
AB  - Optically transparent zebrafish embryos provide an excellent vertebrate model
      system in which to reveal specific mRNA and protein expression patterns during
      development. Whole-mount preparations can be used to generate three-dimensional
      color or fluorescent readouts of the expression pattern of a given gene (or
      genes), matched with a bright-field image of all the tissues in the developing
      embryo. Whole-mount mRNA in situhybridization (WISH) has long been the method of
      choice for revealing gene expression patterns in zebrafish because this method
      depends only on being able to identify a relatively short region of nucleotide
      sequence unique for the gene of interest. In contrast, the scarcity of antibodies
      that are specific to or cross-react with zebrafish proteins has limited the
      widespread use of immunocytochemical applications, though this situation will
      improve in the future. The elucidation of the specific expression patterns of Wnt
      pathway genes in zebrafish has made a major contribution to our current
      understanding of their roles in vertebrate development.

PMID- 19109716
TI  - Manipulation of gene expression during zebrafish embryonic development using
      transient approaches.
AB  - The rapid embryonic development and high fecundity of zebrafish contribute to the
      great advantages of this model for the study of developmental genetics. Transient
      disruption of the normal function of a gene during development can be achieved by
      microinjecting mRNA, DNA or short chemically stabilized anti-sense oligomers,
      called morpholinos (MOs), into early zebrafish embryos. The ensuing develop ment
      of the microinjected embryos is observed over the following hours and days to
      analyze the impact of the microinjected products on embryogenesis. Compared to
      stable reverse genetic approaches (sta ble transgenesis, targeted mutants
      recovered by TILLING), these transient reverse genetic approaches are vastly
      quicker, relatively affordable, and require little animal facility space. Common
      applications of these methodologies allow analysis of gain-of-function (gene
      overexpression or dominant active), loss-of-function (gene knock down or dominant
      negative), mosaic analysis, lineage-restricted studies and cell tracing
      experiments. The use of these transient approaches for the manipulation of gene
      expression has improved our understanding of many key developmental pathways
      including both the Wnt/beta-catenin and Wnt/PCP pathways, as covered in some
      detail in Chapter 17 of this book. This chapter describes the most common and
      versatile approaches: gain of function and loss of function using DNA and mRNA
      injections and loss of function using MOs.

PMID- 19109717
TI  - Neural patterning and CNS functions of Wnt in zebrafish.
AB  - Wnt signaling plays several important roles in the development of the zebrafish
      central nervous system (CNS). This chapter outlines both the known and postulated
      roles of Wnts from the earliest step of neural plate induction to relatively late
      events such as axon pathfinding and synaptogenesis. The common tools useful for
      examining Wnt function and nervous system development in zebrafish are first
      reviewed. Examples are then provided for specific phenotypes resulting from gain
      and loss of Wnt activity at multiple developmental stages. Finally, specific
      assays and reagents that can be used to investigate the function of novel Wnt
      pathway components in CNS development are listed.

PMID- 19109718
TI  - Studying Wnt signaling in Xenopus.
AB  - Xenopus is an established and powerful model system for the study of Wnt
      signaling in vertebrates. Above all, the relatively large size of the embryos
      enables microinjection experiments, which have led to key discoveries not only
      about the functional role of Wnt signaling in vertebrate embryos, but also about
      the molecular mechanisms of Wnt signaling in vertebrate cells. A major advantage
      of the Xenopus model is the ability to obtain large numbers of embryos, which
      develop relatively rapidly and which can be studied in natural separation from
      sentient adult parental animals. In order to obtain Xenopus embryos, ovulation in
      females is induced with a simple hormone injection, the eggs collected and
      fertilized with sperm from males. The Xenopus model system has been further
      strengthened by recent advances such as morpholino technology and efficient
      transgenic methods, as well as the development of Xenopus tropicalis as a diploid
      genetic model system with a shorter generation time and a genome similar to
      higher vertebrates.

PMID- 19109719
TI  - Analysis of gene expression in Xenopus embryos.
AB  - Determining the expression pattern of a gene of interest is critical to
      understanding when, where, and how it may function during development. This
      chapter describes methods for determining the localization and expression levels
      for both mRNA and protein. Some of these methods can be described as quantitative
      or semi-quantitative while others are considered more qualitative in nature. To
      determine the spatial localization of mRNA expression, RNA in situ hybridization
      can be used on both whole-mount or sectioned embryos. Northern blot and qPCR are
      more quantitative methods for analyzing mRNA expression levels. For determining
      protein localization, antibody staining either by immunocytochemistry or
      immunofluorescence can be performed on both whole-mount or sectioned embryos;
      whereas Western blot is the method generally used for quantifying protein
      expression levels.

PMID- 19109720
TI  - Detection of nuclear beta-catenin in Xenopus embryos.
AB  - Immunodetection of beta-catenin accumulation in the nucleus is the most direct
      and reliable method to determine the intensity and the spatial/temporal patterns
      of Wnt-dependent signaling activity. Due to the large size of the Xenopus embryo,
      staining must be done on sections. We present here a simple protocol to prepare
      cryosections and produce high-quality images of the early embryo using
      immunofluorescence. We also provide comments on various conceptual and technical
      issues from fixation to image collection, which may assist in optimizing
      immunodetection in embryos and tissues beyond the specific scope of beta-catenin
      localization.

PMID- 19109721
TI  - Transgenic reporter tools tracing endogenous canonical Wnt signaling in Xenopus.
AB  - Activation of the canonical Wnt pathway leads to the transcriptional activation
      of a particular subset of downstream Wnt target genes. To track this localized
      cellular output in a living organism, reporter constructs can be designed
      containing multimerized consensus lymphoid enhancer binding factor (LEF)-1/T cell
      factor (TCF) transcription factor binding sites, generally referred to as TCF
      optimal promoter (TOP) sites. In Xenopus, several Wnt-responsive reporter systems
      have been designed containing a number of these TOP sites that, in combination
      with a minimal promoter, drive the expression of a reporter gene. Following
      transgenic integration in Xenopus embryos, a Wnt reporter tool reveals the
      spatiotemporal delineation of endogenous Wnt pathway activities throughout
      development. Assumed to be a general readout of the Wnt pathway, such reporters
      can assist in elucidating unknown functional implications in developing Xenopus
      embryos.

PMID- 19109722
TI  - Gain-of-function and loss-of-function strategies in Xenopus.
AB  - Xenopus embryos are particularly suited for functional experiments to investigate
      vertebrate embryonic development. Due to the large size of embryos and their
      development outside of the mother organism, they are very accessible, easy to
      manipulate, and allow for immediate observation of developmental phenotypes.
      Powerful methods have been established for both gain- and loss-of-function
      strategies, which build on these inherent advantages. This chapter describes
      injection methods used to overexpress gene products and inhibit gene expression
      as well as pharmacological approaches to manipulate Wnt signaling in Xenopus
      embryos.

PMID- 19109723
TI  - How the mother can help: studying maternal Wnt signaling by anti-sense-mediated
      depletion of maternal mRNAs and the host transfer technique.
AB  - Early development in Xenopus laevis is controlled by maternal gene products
      synthesized during oogenesis. The dorsal/ventral and anterior/posterior axes are
      established as a result of canonical Wnt signaling activity. The functions of
      maternal genes in embryonic development are most effectively studied by
      introducing anti-sense, oligos complementary to their mRNAs into oocytes and
      culturing the oocytes long enough to allow for the breakdown of the target RNAs
      and the turnover of existing cognate proteins before fertilization. This method
      has been used to establish the role of Wnt signaling in Xenopus axis formation.
      Here we describe the methodology for targeting of maternal mRNAs and for
      successful fertilization of mRNA-depleted oocytes.

PMID- 19109724
TI  - Inducible gene expression in transient transgenic Xenopus embryos.
AB  - Xenopus laevis has for many years been successfully used to study Wnt signaling
      during early development. However, because loss of function and gain of function
      experiments generally involve injecting RNA, DNA, or morpholinos into early
      embryos (1- to 32-cell), major phenotypes are often observed before the embryo
      has reached later stages of development. The combined use of transgenics and a
      heat shock inducible system has overcome these problems and enables
      investigations of Wnt signaling at later stages of Xenopus embryonic development,
      including organogenesis.

PMID- 19109725
TI  - Wnt-frizzled interactions in Xenopus.
AB  - The Wnt signaling cascades are regulatory modules which are involved in embryonic
      patterning, cell differentiation, morphogenesis, and diseases. The Wnt pathways
      are activated when secreted Wnt ligands interact with 7-trans-membrane receptors
      of the Frizzled (Fz) family. Specific readouts are determined by the
      ligand/receptor combinations and the cellular context. Here we describe two
      methods for the analysis of Wnt/Frizzled interactions in Xenopus embryos.
      Physical interaction of ligand and receptor are demonstrated by co
      immunoprecipitation assays. The activation of Wnt targets in Xenopus animal cap
      tissue provides a versatile test system for activating and inhibitory components
      of the Wnt/beta -catenin pathway.

PMID- 19109726
TI  - Dorsal axis duplication as a functional readout for Wnt activity.
AB  - The easy accessibility, distinctive features of early cleavage stage embryos and
      simple manipulation methods make Xenopus embryos an ideal model organism to study
      gene function and deciphering signaling pathways. For many years, investigators
      have analyzed putative dorsalizing factors by their ability to induce secondary
      dorsal structures when misexpressed in early Xenopus embryos. This assay, among
      others, has contributed substantially to our knowledge about Wnt signaling
      pathways and is still the assay of choice to quickly determine whether a factor
      acts positively or negatively in the Wnt signaling pathway. This chapter
      describes two experimental approaches to determine canonical Wnt signaling:
      induction of a secondary axis and analyses of target gene expression.

PMID- 19109727
TI  - Regulation of convergent extension by non-canonical Wnt signaling in the Xenopus
      embryo.
AB  - Non-canonical Wnt signaling is an important regulator of gastrulation in Xenopus.
      In particular, it has been implicated in the control of convergent extension
      movements. Convergent extension in the gastrula occurs primarily in the dorsal
      tissue of the marginal zone, and explants of this tissue will continue to undergo
      these movements in isolation. This observation has led to an assay to examine
      convergent extension movements that is unique to the Xenopus system, and is
      described herein.

PMID- 19109728
TI  - Frizzled-7-dependent tissue separation in the Xenopus gastrula.
AB  - Formation of tissue boundaries can be studied in a simple, inexpensive system,
      the Xenopus gastrula. Here, the internalized mesoderm and endoderm are separated
      from the ectodermal blastocoel roof by Brachet's cleft. Non-canonical Wnt
      signaling mediated by the Wnt receptor, Xfz-7, is essential for this tissue
      separation event. The function of Wnt pathway components and other factors in
      tissue separation at Brachet's cleft can be tested in a blastocoel roof assay.
      Small pieces of mesoderm or endoderm are placed on large blastocoel roof
      explants, and it is observed whether these test explants remain on the surface of
      their in vivo substratum, or sink into it.

PMID- 19109729
TI  - Portrait of a polyp: the CTC dilemma.

PMID- 19109730
TI  - Uncommon cases of immature-type CD56+ natural killer (NK)-cell neoplasms,
      characterized by expression of myeloid antigen of blastic NK-cell lymphoma.
AB  - Immature-type CD56(+) natural killer (NK)-cell neoplasms are classified as either
      myeloid/NK-cell precursor acute leukemia or blastic NK-cell lymphoma. We
      identified two cases of immature-type CD56(+) NK-cell neoplasms that were not
      categorizable as either of these entities. The first case involved a 74-year-old
      woman presenting with skin eruptions and pancytopenia due to bone marrow
      necrosis. Skin biopsy specimen revealed CD4(+), CD7(-), CD34(-), CD43(+),
      CD56(+), CD68(+), muramidase (lysozyme)(+), and myeloperoxidase (MPO)(-), and
      immunophenotyping of peripheral blood showed CD4(+), CD7(-), CD13(+), CD33(+),
      CD34(-), CD43(+), CD56(+), cytoplasmic (cy)CD68(+), CD123(+), and HLA-DR(+). The
      second case involved a 62-year-old man who had bilateral optic nerve tumor and
      presented with malignant cells in peripheral blood. Cell surface markers of
      malignant cells showed CD4(+), CD7(-), CD13(+), CD33(+), CD34(-), CD43(+),
      CD56(+), cyCD68(+), and HLA-DR(+). The phenotypes of tumor cells in both cases
      were compatible with blastic NK-cell lymphoma, except for the expression of
      myeloid antigen. Clinical presentations of these cases showed characteristics of
      both blastic NK-cell lymphoma and myeloid/NK-cell precursor acute leukemia.

PMID- 19109731
TI  - Cytogenetic analysis in childhood acute lymphoblastic leukemia: experience at a
      single institution in Korea.
AB  - We evaluated major cytogenetic abnormalities associated with childhood acute
      lymphoblastic leukemia (ALL) through both fluorescent in situ hybridization and
      conventional chromosomal analysis for 132 ALL patients diagnosed at St Mary's
      Hospital in Korea. Chromosome abnormalities have been detected in 92% of
      patients. Eighteen (14%) patients showed numerical abnormalities only, 50 (38%)
      patients showed structural abnormalities only, and 53 (40%) patients showed both.
      The simultaneous trisomies 4, 10 and 17 were observed in 23 (17%) patients. Of
      the patients with abnormal karyotypes, recurrent structural abnormalities were
      determined in 103 (78%) cases. t(12;21)(q13;q22) was found in 29 (22%) out of 132
      patients, 9p abnormalities in 13 (10%) patients, t(1;19)(q23;p13.3) in 11 (8%)
      patients, t(9;22)(q34;q11.2) in 11 (8%) patients, and 11q23 abnormalities in 7
      (5%) patients. Interestingly, we identified five uncommon translocations such as
      t(5;12) (q33;p13), t(14;19)(q32;q13.1), t(12;16)(p13;q13),
      der(1)t(1;12)(p32;p13), and t(5;15)(p15;q11.2). Our study pool is representative
      of pediatric ALL patients in Korea as it consists of about 20% of patients
      diagnosed annually in Korea. We believe that the data provided will aid in
      comparative studies of the treatment outcomes, as well as the type and incidence
      of chromosomal abnormalities associated with childhood ALL in various Asian
      nations and Western countries.

PMID- 19109732
TI  - Spinal epidural granulocytic sarcoma in non-leukemic patient.
AB  - A previously healthy 24-year-old male presented with a 3-month history of
      progressive backache and weakness in both legs. Magnetic resonance imaging of the
      spine showed a large soft tissue mass infiltrating paraspinal musculature of
      lumbosacral area, sacral laminas, last lumbar and all sacral vertebra, protruding
      into the spinal canal, and with propagation into pelvis. Baseline laboratory data
      were normal. Decompressive laminectomy and tumor removal were performed resulting
      in neurological improvement. Histological examination identified granulocytic
      sarcoma (GS). Bone marrow biopsy showed normal findings. The patient underwent
      adjuvant chemotherapy and radiotherapy, resulting in the elimination of residual
      lesion, followed by autologous transplant. Immediate diagnosis and adequate
      systematic treatment are essential to achieve optimal results in patients with
      isolated GS. The patient is alive and free of the disease 14 months from the
      diagnosis.

PMID- 19109733
TI  - Primary cutaneous diffuse large B-cell lymphoma (leg type) after renal allograft:
      case report and review of the literature.
AB  - We report a case of a 58-year-old man who presented with a rapidly growing
      proliferative lesion on the left lower limb, clinically resembling a soft tissue
      sarcoma 3 years after renal allograft. There was no evidence of systemic
      involvement on bone marrow needle aspiration and computed tomography (CT) scans
      of the chest and abdomen. The lesion turned out to be primary cutaneous diffuse
      large B-cell lymphoma, leg type (PCLBCL LT), as defined in the recent World
      Health Organization-European Organization for Research and Treatment of Cancer
      (WHO-EORTC) classification of cutaneous lymphomas by skin biopsy.
      Immunosuppression reduction, chemotherapy with CHOP regimen and local
      radiotherapy induced complete remission of the tumor.

PMID- 19109734
TI  - Erosive arthritis in systemic lupus erythematosus is associated with high serum C
      reactive protein and anti-cyclic citrullinated peptide antibodies.
AB  - Predictors for erosive arthritis in systemic lupus erythematosus (SLE) are poorly
      understood. We performed a pilot, descriptive case-series study to identify
      whether different biomarkers differentiate SLE patients from those additionally
      developing erosive arthritis. Median C-reactive protein (CRP) concentration in
      erosive arthritis was 14.5 mg/L (IQR, 6.6-19.4), but only 0.8 (0.45-7.37, p =
      0.01) in non-erosive. Anti-cyclic citrullinated peptide antibodies (anti- CCP)
      were also associated with erosive arthritis (60 vs. 0% , p = 0.02; OR = 18.2,
      0.66-495). Serum IL-6, IFNgamma, IL-4 and IL-10 tended to be higher in erosive
      arthritis, although none attained statistical significance. A negative
      correlation between IL-6 and CRP was found in non-erosive arthritis ( r-0.60).
      High CRP and anti-CCP may be useful serological markers for an erosive arthritis
      pattern among SLE patients.

PMID- 19109735
TI  - Exploring the complex relations between inflammation and aging (inflamm-aging):
      anti-inflamm-aging remodelling of inflamm- aging, from robustness to frailty.
AB  - "Inflamm-aging" denotes the up-regulation of certain pro-inflammatory cytokines
      at older ages, and associated chronic diseases. It is well known that blood
      levels of cortisol also increase with age, an increase commonly considered to be
      due to activation of the Hypothalamus- Pituitary- Adrenal (HPA) axis by many non
      specific stressors. On the contrary, herein I describe how the activation of
      Hypothalamus- Pituitary-Adrenal (HPA), far from being unspecific, constitutes: a)
      the main specific response and counterbalance to "Inflammaging" ('anti
      inflammaging'), b) an explanation for the well known paradox of immune
      senescence: i.e. the coexistence of inflammation and immunodeficiency, as well as
      c) a complex mechanism of remodelling elicited by inflammaging, explaining the
      long and winding pathophysiological road that goes from robustness to frailty.
      Indeed, the phenomenon of anti-inflammaging, mainly exerted by cortisol, with the
      passage of time becomes the cause of a marked decline of immunological functions,
      and its coexistence with the increased levels of pro-inflammatory cytokines of
      inflammaging, ultimately have negative impacts on metabolism, bone density,
      strength, exercise tolerance, the vascular system, cognitive function, and mood.
      Thus inflammaging and anti-inflammaging together determine many of the
      progressive pathophysiological changes that characterize the "aged-phenotype",
      and the struggle to maintain robustness finally results in frailty.The same
      consequences also result the age-dependent decline of dehydroepiandrosterone
      (DHEA).

PMID- 19109736
TI  - Regulatory CD4+CD25+ T cells and macrophages: communication between two
      regulators of effector T cells.
AB  - Regulatory T cells (Tregs) play an essential role in the induction and
      maintenance of peripheral tolerance as well as prevention of autoimmunity by
      limiting the strength of the immune response of effector T cells. Macrophages, a
      heterogeneous population of phagocytes and professional antigen presenting cells
      (APCs), can also exert suppressive effects on effector T cells to keep the
      peripheral balance of immunity. The bi-directional interactions of dendritic
      cells (DCs) and Tregs have been cell studied. However, much less is known about
      the reciprocal interaction between macrophages and Tregs. In this review, we will
      discuss recent observations regarding the interplay of these two regulators of
      immunity.

PMID- 19109738
TI  - Leukocyte depletion during cardiac surgery with extracorporeal circulation in
      high risk patients.
AB  - BACKGROUND: Cardiopulmonary bypass is associated with systemic inflammation that
      may contribute to increased perioperative mortality. Depletion of circulating
      leukocytes may reduce the inflammatory response. We studied the effect of a
      leukocyte depleting filter on leukocyte activation during cardiopulmonary bypass
      in high risk patients. METHODS: Fifty patients undergoing coronary artery bypass
      grafting with a preoperative high risk were randomly placed in an arterial line
      leukocyte filter group (n = 25) with a leukocyte depleting filter. Blood sampling
      took place from the arterial line to analyze polymorphnuclear elastase and
      myeloperoxidase at six time points, including: A) before the induction of
      anesthesia, B) before the induction of the cardiopulmonary bypass C) 1 min after
      the release of the aorta clamp, D) the end of the operation, E) 1 h
      postoperative, and F) 24 h postoperative. RESULTS: Levels of polymorphonuclear
      elastase, (PMNE), and myeloperoxidase (MPO) were found to be higher after the
      release of the aortic cross clamp in the leukocyte filter group; these levels
      remained elevated until 24 hours after surgery and were high in comparison to
      preoperative baseline levels. The differences in PMNE between both groups at time
      points C and D (p < 0.005) and E (p < 0.05) were statistically significant. The
      serum levels of the S-100B and neuron specific enolase (NSE) were found to be
      elevated between time points C and E in both groups without statistical
      significance. The in-hospital mortality was 16% (4 patients) in leukocyte filter
      group and 4% in control group (1 patient). CONCLUSIONS: Interestingly, the
      activation of neutrophils was more pronounced in the LF group. The use of a
      leucocyte depleting filter was not advantageous for this patient cohort for
      clinical or biomedical endpoints.

PMID- 19109737
TI  - Effects of high glucose plus high insulin on proliferation and apoptosis of mouse
      endothelial progenitor cells.
AB  - OBJECTIVE: To study the effects of high glucose plus high insulin (GI) on
      proliferation, apoptosis, morphology and differentiation of endothelial
      progenitor cells (EPC). METHODS: EPC were isolated and identified by magnetic
      cell sorting and flow cytometry. EPC proliferation and apoptosis were measured by
      MTT assay and Annexin-V/PI double labeling, respectively. Cell proliferation- and
      apoptosis-related factors were examined by Western blotting. RESULTS: Seven days
      after GI treatment, EPC were arrested at the G(0)/G(1) phase. Treatment with high
      glucose alone (HG) or GI but not HI (high insulin alone) decreased EPC
      proliferation and their expression of cyclin E, cdk2 and PCNA compared to
      control. The inhibitory effects of HG on EPC proliferation and growth-related
      proteins were more significant than those of GI. HG, GI and HI promoted EPC
      apoptosis along with caspase-3 overexpression. CONCLUSION: The result indicated
      that GI-induced apoptosis and growth inhibition might be one of mechanisms of EPC
      reduction and dysfunction in diabetes.

PMID- 19109739
TI  - Antiinflammatory effects of etoricoxib alone and combined with NSAIDs in LPS
      induced reactive arthritis.
AB  - OBJECTIVE: Nonsteroidal anti-inflammatory drugs constitute the primary
      therapeutic approach in reactive arthritis. Here, we compared etoricoxib, a
      specific COX-2 inhibitor, with other cyclooxygenase inhibitors on articular
      incapacitation, edema, leukocyte migration, and gastric damage, in a model of LPS
      induced reactive arthritis in rats. METHODS: E. coli Lipopolysaccharide was
      injected into a carrageenan-primed knee-joint of rats. The effects of etoricoxib,
      piroxicam, indomethacin, as well the combination of etoricoxib either with
      piroxicam or indomethacin, were evaluated on articular incapacitation and edema.
      Afterwards, the synovial leukocyte ontent and the stomach bleeding points were
      counted. RESULTS: Etoricoxib, piroxicam, and indomethacin dose-dependently
      inhibited incapacitation and edema. However, only etoricoxib inhibited both
      mononuclear and polymorphonuclear leukocyte migration. Piroxicam inhibited only
      mononuclear migration, while indomethacin even increased polymorphonuclear
      content in inflamed synovia. Associating etoricoxib with either subeffective
      doses of piroxicam or indomethacin did not enhance the hyponociceptive or the
      antiedematogenic effect, but prevented the anti-leukocyte migration effect and
      increased gastric damage. CONCLUSION: The present results suggest that the
      selective COX-2 inhibitor etoricoxib could be a better option than non-selective
      COX inhibitors, since it presented a potent inhibitory effect on the clinical
      signals and also a potent inhibition on cell migration.

PMID- 19109740
TI  - Tubular epithelial cells have the capacity to transdifferentiate into CD68
      positive macrophage-like cells by oxidative stress.
AB  - OBJECTIVE: The present study was intended to assess transdifferentiation from
      tubular epithelial cells to macrophage- like cells. METHODS: Puromycin
      aminonucleoside nephrotic rats were sacrificed at days 4, 8, 24 and 112. We
      immunohistochemically evaluated CD68, CD163, and cytokeratin AE1/AE3, known as
      markers for macrophages and tubular epithelial cells. Nitrotyrosine, gp91(phox)
      and Rac 1 expressions was also analyzed. CD68 expression in cultured murine
      proximal tubular epithelial cells (mProx) stimulated by crude and pure BSA was
      examined by flow cytometry and immunofluorescence. RESULTS: The tubular CD68
      positive cells were observed on day 112. Immunoelectronmicroscopy revealed that
      some CD68-positive cells showed brush borders on the cell membrane and some of
      cytokeratin-positive tubular cells also expressed CD163 in mirror sections. The
      tubular CD68-positive cells were also positive for nitrotyrosine, gp91 (phox) and
      Rac 1. They contained lipid in their cytoplasm. Crude BSA, containing free fatty
      acid, induced CD68 expression in a dose- and time-dependent manner in mProx, but
      not pure BSA. The surface expression of CD68 was increased by high dose and long
      term stimulation with crude BSA as shown by immunofluorescence. CONCLUSIONS: We
      confirmed that tubular epithelial cells have the capacity to transdifferentiate
      to CD68-positive macrophage-like cells, which may be linked to oxidative stress.

PMID- 19109741
TI  - Platonin inhibits LPS-induced NF-kappaB by preventing activation of Akt and
      IKKbeta in human PBMC.
AB  - OBJECTIVE: Platonin is a potent macrophage-activating agent and an
      immunomodulator. It has been used to treat trauma, ulcers and some acute
      inflammations. Although platonin has desirable anti-inflammatory effects, its
      mechanism of action is not clear. In the present study, we investigated the
      effect of lipopolysaccharide (LPS) on human peripheral blood mononuclear cells
      (PBMC) gene expression and determined the molecular mechanism of platonin action
      in the LPS-induced NF-kappaB signaling pathway. METHODS: In human PBMC,
      treatments with platonin (0.1 microg/ml) suppressed the production of pro
      inflammatory cytokines (IL-1beta, TNF-alpha and IL-6), nitric oxide (NO) and
      multiple kinases (iNOS, COX-2) induced by LPS. We found that the effect of
      platonin on LPS-induced production of pro-inflammatory cytokines and multiple
      kinases was due to the inhibition of NF-kappaB activity. Additional work revealed
      that this inhibition was caused by a reduction in the phosphorylation and
      subsequent degradation of IkappaBalpha. Further investigation revealed that Akt
      and IkappaB kinase beta (IKKbeta) activity were also inhibited during platonin
      treatment, which may be what prevented NF-kappaB from entering the nucleus and
      activating gene transcription. CONCLUSIONS: These results suggest the anti
      inflammatory activity of platonin is a result of reduced NF-kappaB activity due
      to inhibition of Akt and IKKbeta.

PMID- 19109742
TI  - Cigarette smoking and innate immunity.
AB  - Cigarette smoking is a worldwide epidemic and the most prevalent cause of many
      diseases leading to increased morbidity and mortality globally. The impact of
      smoking on pathogenesis of cancer is being extensively studied however cigarette
      smoke as an immunosuppressant is less well recognized. Here we review the
      immunosuppressive effects of cigarette smoke and the mechanisms by which smoking
      affects host innate immunity including structural and functional changes in the
      respiratory ciliary epithelium, lung surfactant protein, and immune cells such as
      alveolar macrophages, neutrophils, lymphocytes and natural killer (NK) cells.
      Thus smoking cessation should be emphasized not only for prevention of cancer and
      coronary artery disease but also for patients with recurrent infections and
      immunosuppressive states.

PMID- 19109743
TI  - Hydrogen sulphide is pro-inflammatory in haemorrhagic shock.
AB  - OBJECTIVE: H(2)S is pro-inflammatory in inflammatory models, thus we investigated
      whether H(2)S plays a role in haemorrhagic shock (HS)-associated inflammation.
      METHODS: Male, Sprague-Dawley rats were given an inhibitor of H(2)S biosynthesis,
      DL-propargylglycine (PAG, 50 mg/kg, i. v.) or saline (1 ml/kg) 30 min before
      blood withdrawal and subjected to HS (mean arterial pressure (MAP) of 40 mM Hg
      for 90 min) followed by reinfusion of shed blood. Animals were killed at 5, 90,
      270 and 630 min after reinfusion. RESULTS: Pre-treatment of animals with PAG 1)
      increased the HR recovery rate (n = 6 - 12, P < 0.05); 2) attenuated the increase
      in plasma levels of TNF-alpha and IL-6 and reduced lung iNOS expression levels (n
      =5 P, < 0.05); and 3) attenuated the increase in plasma levels of ALT and reduced
      HS-induced increase in liver and lung myeloperoxidase (MPO) activity (n = 5, P <
      0.05). CONCLUSIONS: H(2)S is pro-inflammatory in HS and inhibition of H(2)S
      biosynthesis may reduce some HS-induced inflammatory responses and organ injury.

PMID- 19109744
TI  - Digoxin and digoxin-like immunoreactive factors (DLIF) modulate the release of
      pro-inflammatory cytokines.
AB  - OBJECTIVE: Cardiac glycosides such as digoxin and their endogenous counterpart
      digoxin-like immunoreactive factor (DLIF) may possess anti-inflammatory
      properties. METHODS: Pro-inflammatory cytokines from human peripheral blood
      mononuclear cells (PBMC) were measured by ELISA using specific antibodies.
      Immunocytochemistry was used to localize NF-K: B. RESULTS: Non-stimulated PBMC
      constitutively secreted minimum amounts of cytokines. LPS (1 mg/L) stimulation
      lead to steep increases in TNF-alpha, IL-6 and IL-8 concentrations with peak
      rises at 8 h. An 8 h delay was observed for IL-10. Increases in IL-10 were
      sustained for18 h period. Significant inhibition (P > 0.05) of TNF-alpha, IL-6
      and IL-8 at non-toxic of digoxin concentration (< 100 nM) and DLIF (10 nM digoxin
      equivalent (de)) was observed whereas no such effect was seen for IL-10.
      Inhibition of the degradation of activated NF-K: B in the PBMC was observed with
      the indicated concentrations of digoxin, DLIF or Pyrrolidine dithiocarbamate
      (PDTC). CONCLUSION: Digoxin and DLIF inhibit the release of proinflammatory
      cytokines from PBMC via NF-K: B-dependent pathway suggesting an anti-inflammatory
      effect.

PMID- 19109745
TI  - Ivermectin inhibits LPS-induced production of inflammatory cytokines and improves
      LPS-induced survival in mice.
AB  - OBJECTIVE AND DESIGN: To investigate whether ivermectin, a semi-synthetic
      derivative of a family of macrocyclic lactones could inhibit lipopolysaccharide
      (LPS)-induced inflammation in vivo and in vitro. MATERIALS AND METHODS: C57BL/6
      mice were administered ivermectin (or saline) orally and challenged
      intraperitoneally with LPS at a lethal dose of 32 mg/kg. RAW 264.7 murine
      macrophages were stimulated with LPS at 1 microg/ml, with or without ivermectin
      for 6, 12 and 24 h. The production of tumor necrosis factor-alpha (TNF-alpha),
      interleukin-1ss (IL-1ss) and interleukin-6 (IL-6) in serum from mice and
      supernatants from cells were measured by ELISA. Nuclear factor-kB (NF-kB)
      translocation with subunit p65 was evaluated by immunocytochemical analysis.
      RESULTS: Ivermectin improved mouse survival rate induced by a lethal dose of LPS.
      In addition, ivermectin significantly decreased the production of TNF-alpha, IL
      1ss and IL-6 in vivo and in vitro. Furthermore, ivermectin suppressed NF-kB
      translocation induced by LPS. CONCLUSIONS: The results indicate that ivermectin
      may inhibit LPS-induced production of inflammatory cytokines by blocking NF-kB
      pathway and improve LPS-induced survival in mice. This finding might provide a
      new strategy for the treatment of endotoxemia and associated inflammation.

PMID- 19109746
TI  - Presence and distribution of biogenic amines (histamine, serotonin and
      epinephrine) in immunophenotyped human immune cells.
AB  - OBJECTIVE: In animal experiments many hormones were demonstrated in immune cells.
      However, very few data are at our disposal in the case of human immune cells. In
      an earlier experiment, ACTH, endorphin and T(3) were studied and found in
      different subsets of human immune cells. Here, three biogenic amines (histamine,
      serotonin and epinephrine) were studied. METHODS: Biogenic amine content of
      immunophenotyped human lymphocytes from 15 blood donors were investigated by
      multicolor flow cytometry using anti-biogenic amine antibodies. Monocytes and
      granulocytes separated by size and granularity were also studied. RESULTS: Each
      biogenic amine could be detected in each subset of leukocytes, except epinephrine
      and serotonin in granulocytes. Activated T cells contained a higher amount of the
      amines, and CD19+B cells a higher amount of histamine, related to the whole
      lymphocyte population and to other subsets. Monocytes contained more histamine
      and epinephrine than lymphocytes and granulocytes contained twice as much
      histamine as monocytes and three times as much as lymphocytes. CONCLUSION: Human
      lymphocytes contain the three biogenic amine, similar to rat. However, while each
      amine was present in monocytes, in granulocytes serotonin and epinephrine were
      not demonstrated. The results call attention to the possible extrapolation of
      animal data to human lymphocytes and monocytes, but in the case of granulocytes,
      caution is needed. Taking into consideration earlier results, activated T cells
      appear to have an important role in the loss or production of hormones inside the
      immune system.

PMID- 19109747
TI  - The allergic inflammatory reaction in neonatal streptozotocininduced diabetic
      rats: evidence of insulin resistance and microvascular dysfunction.
AB  - OBJECTIVE: To investigate the allergic reaction in neonatal streptozotocin (nSTZ)
      induced diabetes mellitus. MATERIAL: Male newborn Wistar rats were made diabetic
      by the injection of streptozotocin (160 mg/kg, i. p.) and used 8 weeks
      thereafter. TREATMENT: Animals were sensitized against ovalbumin (OA, 50 microg
      and Al(OH)3, 5 mg, s. c.) and challenged 14 or 21 days thereafter. METHODS: OA
      induced airway inflammation and OA-induced pleurisy models were used to
      investigate leukocyte migration (total and differential leukocyte counts) and
      lung vascular permeability (Evans blue dye extravasation). RESULTS: nSTZ-diabetic
      rats presented glucose intolerance and insulin resistance. Relative to controls,
      nSTZ rats exhibited a 30% to 50% reduction in lung vascular permeability.
      Leukocyte infiltration in both models of allergen-induced inflammation, and
      number of pleural mast cells did not differ between groups. CONCLUSIONS: Data
      suggest that the reduction of allergic inflammatory reactions in nSTZ rats is
      restricted to microvascular dysfunctions and associated, probably, with insulin
      resistance in lung microvascular endothelium.

PMID- 19109748
TI  - Autoregulative function in the brain in an endotoxic rat shock model.
AB  - OBJECTIVE AND DESIGN: Autoregulative function in the brain gets relevant in
      hypodynamic conditions of a sepsis syndrome. We investigated the temporal pattern
      and dose dependent effects of LPS-induced shock on autoregulative function in
      rats. MATERIAL AND SUBJECTS: Chloralose-anesthetized and mechanically ventilated
      male CD-rats (n = 30). TREATMENT: Animals were subjected to vehicle, 1 or 5 mg/kg
      b.w. lipopolysaccharide (LPS) from E. coli given intravenously. METHODS:
      Autoregulative function was tested repeatedly with a carotid compression
      technique assessing the transient hyperemic response ratio (THRR) in the cortex
      with laser Doppler flowmetry up to 270 min. THRR data from exsanguination
      experiments served as controls. RESULTS: Despite lower blood pressure levels in
      the high dose group (control: 114 +/- 7 mmHg; 1 mg/kg LPS group: 82 +/- 16 mmHg;
      5 mg/kg LPS group: 62 +/- 16 mmHg; p < 0.05) progressive cerebral hyperemia
      occurred similarly in both groups. Compared to exsanguinations experiments
      autoregulative compensation for lower blood pressure levels was lacking in the
      high LPS dose group at the end of experiments. CONCLUSIONS: Cerebral
      autoregulation was affected by LPS-induced shock supporting the notion of
      vasoregulative failure in endotoxic shock.

PMID- 19109749
TI  - Dynamics of neutrophilic NF-kB translocation in relation to IL-8 mRNA expression
      after major trauma.
AB  - OBJECTIVE: Systemic inflammation subsequent to polytrauma is connected to
      neutrophil (PMN) dysregulation characterized by reduced NF-kB-translocation and
      cytokine expression. The dynamics of NF-kB-activation as well as its down-stream
      regulation of IL-8-expression in PMN following major trauma remain unclear. The
      aim of this pilot study was to analyse NF-kB nuclear translocation in relation to
      IL- 8-mRNA-expression in PMN after major trauma. PATIENTS AND METHODS: PMN were
      isolated from blood samples of 15 major trauma patients (New Injury Severity
      Score, NISS > 16) drawn within 90 min and subsequently 6, 12, 24, 48, 72 h after
      trauma. NF-kB-translocation was analysed by Electrophoretic Mobility Shift Assay,
      EMSA and quantified by densitometry [arbitrary units], IL-8-mRNA-expression by RT
      PCR, [copies/50 ng RNA]. Additionally, NF-kB-translocation and IL-8-expression in
      PMN of healthy volunteers were analysed natively (-control) and after LPS
      stimulation (+control). RESULTS: NF-kB-translocation and IL-8-mRNA-expression was
      significantly increased in polytrauma patients (n=15; NISS: 34 +/- 8 [mean +/-
      SEM]) initially. In non-survivors, NFkB- translocation was significantly
      increased on admission and subsequently reduced within 6 h, while it increased in
      the survivors group. After 24 h, a second significant increase in NF-kB-activity
      and IL-8-expression was found in survivors that was subsequently reduced in both
      groups. CONCLUSION: This pilot study has shown that a concomitant initial
      increase in transcriptional NF-kB-activity and IL-8 mRNA expression was observed
      in the early posttraumatic period which preceded the down-regulation of the
      innate immune system.

PMID- 19109750
TI  - Wine and health: state of proofs and research needs.
AB  - Regular moderate wine consumption is often associated with reduced morbidity and
      mortality from to a variety of chronic diseases in which inflammation is a root
      cause. Wine comes in a wide variety of styles that contain quite different
      ethanol and polyphenol contents. Controversy remains as to whether the alcohol or
      polyphenols contribute more to the health benefits of regular moderate wine
      consumption. The variety of wines available to consumers can be expected to
      affect health differently in accordance with a particular wine's total
      polyphenolic content and spectrum of individual polyphenols. The overall effect
      of wine consumption on health depends upon the total amounts consumed, the style
      and possibly the pattern of consumption. The apparent effect of wine consumption
      may be modified by the non-wine diet composition of the consumer in that alcohol
      may appear as the primary component in consumers with high fruit, vegetable and
      whole grain intakes while phytochemical benefit may become significant in diets
      where wine is the primary dietary source of phytochemical. In this review, wine
      polyphenol mechanisms of action will be reviewed in connection with the mechanism
      the development of atherosclerotic cardiovascular disease (ASCVD). Selected
      clinical studies published in 2004-2008 were reviewed. Experimental requirements
      for valid clinical studies, translation of in vitro to in vivo application and
      areas where additional evidence needs to be developed were identified.

PMID- 19109751
TI  - Modulation of inflammatory mediators by coumarinolignoids from Cleome viscosa in
      female swiss albino mice.
AB  - The effect of coumarinolignoid cleomiscosins A, B and C isolated from the plant
      Cleome viscosa on inflammatory mediators were studied in female swiss albino
      mice. A mixture of coumarinolignoid A, B, and C at 10, 30 and 100 mg/kg body
      weight once a day for 14 consecutive days were administered orally to the mice.
      Pro-inflammatory mediators such as IL-6, TNF-alpha and nitric oxide were
      estimated from culture supernatant obtained from peritoneal macrophages
      stimulated by LPS and anti-inflammatory mediator IL-4 was estimated from culture
      supernatant obtained from spleenocytes stimulated by Con-A. For further
      confirmation, expressions of inflammatory mediators from serum and mortality rate
      were studied in LPS-induced toxicity model in mice. The expression of Pro
      inflammatory mediators was significantly (P <0.05) decreased in coumarinolignoids
      treatment group in dose dependent manner, whereas the anti-inflammatory mediator
      expression was significantly increased in coumarinolignoids at 10 mg/kg
      treatment. Mortality rate was also significantly reduced in treatment group in
      LPS-induced toxicity model. The result of this study concluded that the oral
      administration of coumarinolignoids inhibited the pro-inflammatory mediators and
      enhances the production of anti-inflammatory mediator in dose dependent manner.

PMID- 19109752
TI  - The clinical assessment of transitional vertebrae and back pain.
AB  - This study examines the relationship between radiological evidence of lumbar
      transitional vertebrae (LTV) and the clinical presentation of low back pain
      (LBP). A retrospective review of 232 consecutive patients presenting at a
      specialist musculo-skeletal clinic with LBP was conducted. The medical chart for
      each patient was reviewed for: gender, birth date, symptoms, physical findings,
      imaging results, and medications prescribed. Subjects were recognized as having a
      lumbar transitional vertebra if it was noted on their x-ray report. The
      prevalence of LTV was 9.5 %. This study is consistent with previous research,
      indicating that the prevalence of LTV is not significantly higher amongst
      patients with LBP. However, this study also provides further detail about the
      clinical presentation and management of patients with LTV. The information
      presented in this study will assist health care professionals in determining the
      clinical significance of a LTV seen on an x-ray film or noted in a radiologist's
      report.

PMID- 19109756
TI  - Associations of self-rated health with different forms of leisure activities
      among ageing people.
AB  - OBJECTIVES: This study examined associations between self-rated health and
      specific forms of leisure activities - i. e. singing in a choir, art painting,
      playing music; art exhibitions, theatre, movies, concerts; religious events;
      studying and self-development; voluntary work - and investigated how confounding
      factors contribute to these associations among ageing people in Finland. METHODS:
      A postal survey was conducted in 2002 among men and women born in 1926-30, 1936
      40 and 1946-50. The final 2,815 participants represented 66% of the original
      sample drawn, stratified by age, gender, and municipality. Logistic regression
      analyses were used to investigate associations between specific forms of leisure
      activities and self-rated health. RESULTS: Going to art exhibitions, theatre,
      movies, and concerts among women and studying and self-development among men were
      significantly positively related to self-rated health, even after adjusting for
      socioeconomic status (SES), other sociodemographic variables, obesity, and health
      behaviours. Among women, active participation in religious events and voluntary
      work were negatively associated with self-rated health. CONCLUSIONS: The
      association of leisure activities and good self-rated health may differ for
      genders due to their nature or meaning. Partial support was found for the
      assumption that leisure activities go together with better self-rated health
      among ageing people.

PMID- 19109757
TI  - Removal of estrogenic activity of iso-butylparaben and n-butylparaben by laccase
      in the presence of 1-hydroxybenzotriazole.
AB  - In the presence of a redox mediator, 1-hydroxybenzotriazole (HBT), iso
      butylparaben (iso-BP) and n-butylparaben (n-BP) were treated with laccase from
      white rot fungus Trametes versicolor. HPLC analysis demonstrated that iso-BP and
      n-BP almost completely disappeared from the reaction mixture after 4 h of
      treatment with the laccase-HBT system. Using the yeast two-hybrid assay system,
      it was also confirmed that the laccase-HBT system substantially removed the
      estrogenic activity of iso-BP and n-BP after 4 h of treatment. Furthermore, there
      was a linear relationship between the removal of estrogenic activity of both
      parabens and the decrease in their concentrations. These results demonstrate that
      the laccase-HBT system is effective in eliminating iso-BP and n-BP, and removing
      the estrogenic activity of both parabens.

PMID- 19109758
TI  - Etiology of testicular germ cell tumors: lumping or splitting? A plea against
      lumping.

PMID- 19109759
TI  - Sex ratio patterns according to Asian ethnicity in Quebec, 1981-2004.
AB  - Elevated ratios of male to female births are emerging in Asian countries due to
      selective abortion of female foetuses. Little research has evaluated the
      possibility of sex selection among Asians in the West. We evaluated patterns in
      the secondary sex ratio (SSR, number of male per 100 female births) according to
      ethnicity in Quebec, Canada. We performed a population-based retrospective
      analysis of live and still births in urban Quebec, 1981-2004 (N = 1,612,614 live
      births). Outcomes included: (1) first and second order SSR over four consecutive
      6-year intervals analysed according to parental mother tongue, parental birth
      region, and mothers still speaking her mother tongue at home, (2) adjusted
      relative risk (RR) of female birth by parental ethnicity, and (3) estimated
      number of unborn females. For the period 1987-1992, first order SSRs were
      elevated (range 118-121) for Indo-Pakistani parental mother tongue and mothers
      currently speaking Indo-Pakistani at home. Second order SSRs were not elevated.
      For Indo-Pakistani mother tongues, the RR of female birth was lower than
      French/English in the same period (adjusted RR 0.96, 95% CI 0.92-0.99). SSRs were
      not imbalanced in the late 1990s among Indo-Pakistani parents, or among Chinese
      ethnicity in any study period. The SSR in Quebec was elevated in the 1980s and
      early 1990s among firstborn relative to subsequent born infants of Indo-Pakistani
      descent. The reason for this imbalance is unclear. Further research in other
      Western settings is necessary to evaluate the possibility of sex selection.

PMID- 19109760
TI  - Protein and energy utilization and the requirements for maintenance in juvenile
      mulloway (Argyrosomus japonicus).
AB  - This study describes the digestible protein (DP) and digestible energy (DE)
      utilization in juvenile mulloway, and determined the requirements for
      maintenance. This was achieved by feeding triplicate groups of fish weighing 40
      or 129 g held at two temperatures (20 or 26 degrees C), on a commercial diet
      (21.4 g DP mJ DE(-1)) at four different ration levels ranging from 0.25% of its
      initial body weight to apparent satiation over 8 weeks. Weight gain and protein
      and energy retention increased linearly with increasing feed intake. However,
      energy retention efficiency (ERE) and protein retention efficiency (PRE)
      responses were curvilinear with optimal values, depending on fish size,
      approaching or occurring at satiated feeding levels. Maximum predicted PRE was
      affected by body size, but not temperature; PRE values were 0.50 and 0.50 for
      small mulloway, and 0.41 and 0.43 for large mulloway, at 20 and 26 degrees C
      respectively. ERE demonstrated a similar response, with values of 0.42 and 0.43
      for small, and 0.32 and 0.34 for large mulloway at 20 and 26 degrees C
      respectively. Utilization efficiencies for growth based on linear regression for
      DP (0.58) and DE (0.60) were independent of fish size and temperature. The
      partial utilization efficiencies of DE for protein (k (p)) and lipid (k (l))
      deposition estimated using a factorial multiple regression approach were 0.49 and
      0.75 respectively. Maintenance requirements estimated using linear regression
      were independent of temperature for DP (0.47 g DP kg(-0.7) day(-1)) while
      maintenance requirements for DE increased with increasing temperature (44.2-49.6
      kJ DE kg(-0.8) day(-1)). Relative feed intake was greatest for small mulloway fed
      to satiation at 26 degrees C and this corresponded to a greater increase in
      growth. Large mulloway fed to satiation ate significantly more at 26 degrees C,
      but did not perform better than the corresponding satiated group held at 20
      degrees C. Mulloway should be fed to satiation to maximize growth potential if
      diets contain 21.4 g DP mJ DE(-1).

PMID- 19109761
TI  - Evaluation of left atrial functions by color tissue Doppler imaging in adults
      with body mass indexes >or=30 kg/m(2) versus those <30 kg/m (2).
AB  - Evaluation of atrial function has received less attention than that of the
      ventricle although normal atrial function is required for optimal overall cardiac
      function. Obesity is associated with increased cardiovascular morbidity and
      mortality. In this study, we compared left atrial functions in obese adults (body
      mass index = BMI >or=30 kg/m(2)) with those in non-obese adults (BMI <30 kg/m(2))
      by color tissue Doppler parameters. There were 37 adults with BMI >or=30 kg/m(2)
      (mean age 36 +/- 11 years) and 26 adults with BMI <30 kg/m(2) (mean age 35 +/- 5
      years). Mean BMI was 38 +/- 6 kg/m(2) in the obese group whereas that was 24 +/-
      2 kg/m(2) in the non-obese group. For color tissue Doppler imaging, sample
      volumes were placed on the mid left atrium at the septum, lateral, inferior, and
      anterior walls. The peak systolic strain (S(s)), peak systolic strain rate
      (SR(s)), peak early diastolic SR (SR(e)), peak late diastolic SR (SR(a)), peak
      systolic tissue velocity (TV(s)), peak early diastolic TV (TV(e)) and peak late
      diastolic TV (TV(a)) values were measured. For each measurement, values in three
      consecutive cardiac cycles were measured and then averaged. To simplify the
      analysis, the values at each wall were combined and averaged to obtain mean
      values. All left atrial systolic function parameters (S(s), SR(s), TV(s)) were
      similar between the groups. In addition, there was no statistically significant
      difference at left atrial diastolic function parameters (SR(e), SR(a), TV(e),
      TV(a)). We could not find any significant difference between obese and non-obese
      adults at left atrial functions assessed by color tissue Doppler parameters.

PMID- 19109763
TI  - Another formula for calculating the gene change rate in real-time RT-PCR.
AB  - Relative quantification real-time PCR has become a routine method in molecular
      biology research to study the small amount gene expression. There are a few
      mathematical models for relative quantification data analysis in real-time PCR,
      and the formula 2(-DDCT ) is one of the most frequently used method. In this
      paper, we are to present another equation which directly calculates the change
      rate (R (c)) of gene expression, and give a example to compare the application of
      this model with 2(-DDCT).

PMID- 19109762
TI  - Selection of housekeeping genes for gene expression studies on the development of
      fruit bearing shoots in Chinese jujube (Ziziphus jujube Mill.).
AB  - Chinese jujube (Ziziphus jujube Mill.) is important economically for its fruit
      and also bears attractive medical value. Its flower development concurs with the
      growth of current fruit bearing shoots (FBSs). However, events involved in
      current FBSs, including FBS differentiation, flower development, and reliable
      housekeeping gene are still unknown. In this study, the morphology of FBS
      development and floral formation were examined and expression profiles of several
      potential internal control genes was determined. These included genes encoding
      proteins involved in protein translation (translation elongation factor 1alpha,
      ZjEF1), protein folding (cyclophilin, ZjCyP) or degradation (ubiquitin extension
      protein, ZjUBQ), and proteins involved in the structure of the cytoskeleton (beta
      actin, ZjACT) or nucleosome (histone3, ZjH3). Our results showed that the floral
      development in early growing FBSs (less than 20 mm in length) or shoot apices was
      not complete. Among ZjACT, ZjEF1, ZjCyP, ZjUBQ, and ZjH3, ZjH3 was the most
      suitable housekeeping gene to evaluate FBS development, based on their expression
      in early growing FBSs, shoot apices, and different organs. These results will be
      useful for further molecular mechanism study about FBS development in Chinese
      jujube.

PMID- 19109764
TI  - An investigation of hormesis of trichloroethylene in L-02 liver cells by
      differential proteomic analysis.
AB  - Hormesis is the dose-response pattern of the biological responses to toxic
      chemicals, characterized by low-dose stimulation and high-dose inhibition.
      Although it is known that some cell types exhibit an adaptive response to low
      levels of cytotoxic agents, its molecular mechanism is still unclear and it has
      yet to be established whether this is a universal phenomenon that occurs in all
      cell types in response to exposure to every chemical. Trichloroethylene (TCE) is
      an organic solvent widely used and is released into the atmosphere from
      industrial degreasing operations. Acute (short-term) and chronic (long-term)
      inhalation exposure to trichloroethylene can affect the human health. In order to
      elucidate a cell-survival adaptive response of L-02 liver cells exposed to low
      dose of TCE, CCK-8 assay was used to assess cytotoxicity, and examined the
      possible mechanisms of hormesis by proteomics technology. We found that exposure
      of L-02 liver cells to low level of TCE resulted in adaptation to further
      exposure to higher level, about 1,000 protein-spots were obtained by two
      dimensional electrophoresis (2-DE) and five protein spots were identified by
      matrix-assisted laser desorption/ionization mass spectrometry and tandem mass
      spectrometry sequencing of tryptic peptides. Our results suggest that a
      relationship may exist between identified proteins and TCE-induced hormesis,
      which are very useful for further study of the mechanism and risk assessment of
      TCE.

PMID- 19109766
TI  - A meta-analysis of acupuncture combined with opioid receptor agonists for
      treatment of opiate-withdrawal symptoms.
AB  - This review extends a prior meta-analysis of acupuncture's utility for treating
      opioid detoxification, addressing the efficacy of acupuncture when combined with
      allopathic therapies. Both English and Chinese databases were searched for
      randomized trials comparing acupuncture combined with opioid agonist treatment
      versus opioid agonists alone for treating symptoms of opioid withdrawal. The
      methodological quality of each study was assessed with Jadad's scale (1-2 = low;
      3-5 = high). Meta-analysis was performed with fixed- or random-effect models in
      RevMan software; the outcome measures assessed were withdrawal-symptoms score,
      relapse rate, side effects, and medication dosage. Withdrawal-symptom scores were
      lower in combined treatment trials than in agonist-alone trials on withdrawal
      days 1, 7, 9, and 10. Combined treatment also produced lower reported rates of
      side effects and appeared to lower the required dose of opioid agonist. There was
      no significant difference on relapse rate after 6 months. This meta-analysis
      suggests that acupuncture combined with opioid agonists can effectively be used
      to manage the withdrawal symptoms. One limitation of this meta-analysis is the
      poor quality of the methodology of some included trials. High-quality studies are
      needed to confirm findings regarding the side effects and medication dosage.

PMID- 19109768
TI  - In Memoriam: John William Daly (1933-2008).

PMID- 19109767
TI  - Alterations in oxidative markers in the cerebellum and peripheral organs in MPS I
      mice.
AB  - Mucopolysaccharidosis type I is a lysosomal storage disease with alterations in
      several organs. Little is known about the pathways that lead to the pathology.
      Evidences point oxidative stress on lysosomal storage diseases and
      mucopolysaccharidosis type I. The aim of the present study was to evaluate
      oxidative biomarkers on mucopolysaccharidosis type I mice model. We evaluated
      antioxidant enzymatic activity, protein damage and lipid peroxidation in the
      forebrain, cerebellum, heart, lung, diaphragm, liver, kidney and spleen.
      Superoxide dismutase activity was increased on cerebellum, lung, diaphragm, liver
      and kidney of mucopolysaccharidosis type I mice. Catalase activity was increased
      on cerebellum, spleen and lung. There was no alteration on glutathione peroxidase
      activity on any of the analyzed organs. Mucopolysaccharidosis type I mice showed
      increased carbonyl groups on cerebellum, heart and spleen. There was a decrease
      of thiobarbituric acid-reactive substances on the cerebellum of
      mucopolysaccharidosis type I mice. The results indicate a oxidative imbalance in
      this model. As lysosomes are very susceptible to oxidative damage, leading
      inclusive to cellular death, and lysosomal storage diseases present several
      alterations on this organelles, this finding can help to elucidate the cellular
      damage pathways on mucopolysaccharidosis type I.

PMID- 19109769
TI  - A career perspective on the discipline of neurochemistry.

PMID- 19109770
TI  - Sensitivity analysis for unmeasured confounding in a marginal structural Cox
      proportional hazards model.
AB  - Sensitivity analysis for unmeasured confounding should be reported more often,
      especially in observational studies. In the standard Cox proportional hazards
      model, this requires substantial assumptions and can be computationally
      difficult. The marginal structural Cox proportional hazards model (Cox
      proportional hazards MSM) with inverse probability weighting has several
      advantages compared to the standard Cox model, including situations with only one
      assessment of exposure (point exposure) and time-independent confounders. We
      describe how simple computations provide sensitivity for unmeasured confounding
      in a Cox proportional hazards MSM with point exposure. This is achieved by
      translating the general framework for sensitivity analysis for MSMs by Robins and
      colleagues to survival time data. Instead of bias-corrected observations, we
      correct the hazard rate to adjust for a specified amount of unmeasured
      confounding. As an additional bonus, the Cox proportional hazards MSM is robust
      against bias from differential loss to follow-up. As an illustration, the Cox
      proportional hazards MSM was applied in a reanalysis of the association between
      smoking and depression in a population-based cohort of Norwegian adults. The
      association was moderately sensitive for unmeasured confounding.

PMID- 19109772
TI  - Cancer occurrence.
AB  - In this chapter, we describe the variability of cancer occurrence by using
      measures of incidence, mortality, prevalence, and survival, according to
      demographic characteristics such as age, sex, socioeconomic status, and
      race/ethnicity, as well as geographic location and time period. We also discuss
      the variability of cancer occurrence in relation to changes in risk factors,
      screening rates, and improved treatments. The variation according to risk factors
      provides strong evidence that much of cancer is caused by environmental factors
      and is potentially avoidable.

PMID- 19109771
TI  - Using a social justice approach to prevent the mental health consequences of
      heterosexism.
AB  - Albee's social justice approach to prevention offers a framework for
      understanding the detrimental effect of heterosexism on lesbian, gay, and
      bisexual (LGB) people. Minority stress models likewise address the role of
      discrimination and other social injustices in contributing to psychological
      distress in minority populations. This article describes Albee's framework in the
      context of minority stress theory as it applies to LGB people and suggests
      activities mental health professionals can engage in to help prevent the
      psychological consequences of heterosexism.

PMID- 19109773
TI  - Cancer registry databases: an overview of techniques of statistical analysis and
      impact on cancer epidemiology.
AB  - Cancer registries provide systematically collected information on cancer
      incidence, prevalence, mortality, and survival of different cancers. Aggregated
      and de-identified patient-level information on cancer is available for analysis
      from individual cancer registries, nationally from the Surveillance,
      Epidemiology, and End Results program, the Centers for Diseases Control and
      Prevention, the North American Association of Central Cancer Registries; and
      internationally from the International Association of Cancer Registries. Over the
      past few decades, the type and extent of cancer-related information captured by
      different cancer registries have been greatly expanded by linkage with other
      population-based information sources, such as the census data and the Centers for
      Medicare and Medicaid Services claims data. In addition, sophisticated
      statistical analytical techniques have been developed that have greatly expanded
      the traditional purview of cancer registries focused on descriptive epidemiology
      and disease quantification to a much broader analytical horizon ranging from
      study of cancer etiology; rare cancers in specific demographic groups;
      interaction of environmental and genetic factors in causation of cancer; impact
      of co-morbidities, race, geographic, socioeconomic, and provider-related factors
      on access, diagnosis, and treatment; outcomes and end results of cancer
      treatment; and cancer control initiatives to diverse areas of cancer care
      disparity, public health policy, public health education, and importantly, cost
      effectiveness of cancer care. Thus, it is not surprising that cancer registries
      have increasingly become indispensable parts of local, national, and
      international cancer control programs, and it is certain that cancer registries
      will continue to be extraordinary resources of information for clinicians,
      researchers, scientists, policy makers, and the public in our fight against
      cancer.

PMID- 19109774
TI  - Breast cancer in Asia.
AB  - Breast cancer is the commonest cancer in most countries in Asia. The incidence
      rates remain low, although increasing at a more rapid rate than in western
      countries, due to changes in the lifestyle and diet. There are many differences
      between breast cancer in Asia compared with western countries. The mean age at
      onset is younger than in the west, and unlike the west, the age-specific
      incidence decreases after the age of 50 years. Because there is no population
      based breast cancer screening program in the majority of Asian countries, the
      majority of patients present with advanced disease. There is a higher proportion
      of hormone receptor-negative patients, and some evidence that the cancers in Asia
      are of a higher grade. Most of the Asian countries are low- and middle-income
      countries, where access to effective care is limited. Because of the late
      detection and inadequate access to care, survival of women with breast cancer in
      Asia is lower than in western countries. Improving breast health in most of the
      Asian countries remains a challenge that may be overcome with collaboration from
      multiple sectors, both public and private.

PMID- 19109775
TI  - Cancer epidemiology in the United States: racial, social, and economic factors.
AB  - It is widely accepted that there is a differential burden of cancer in certain
      populations, including racial/ ethnic minorities, the medically underserved, and
      older adults. Differences in survival, stage at diagnosis, and risk of death have
      been identified in these populations for cancers of the lung, colon and rectum,
      prostate, and female breast. The factors that drive these disparities are not
      uniformly understood. Addressing the unique issue of racial differences in cancer
      epidemiology necessitates a discussion of the definitions of "race" and
      "ethniCity," and an analysis of the validity of these concepts within the context
      of scientific study. Poor cancer-related health outcomes in groups of low
      socioeconomic status highlight issues of access to care and preventive care use.
      There is a scant amount of data on cancer in the elderly, and the special
      considerations that this group faces. A unique challenge facing cancer
      epidemiologists is suboptimal recruitment of members of these groups into
      clinical studies, which precludes a robust understanding of the existing
      disparities. It is critical to appreciate the overlap that exists between these
      populations, because this may complicate data interpretation. Legislative efforts
      that have, in part, been driven by the National Center on Minority Health and
      Health Disparities and by the Department of Health and Human Services, will
      continue to play an instrumental role in the identification and resolution of
      cancer disparities in these groups.

PMID- 19109776
TI  - Epidemiology of multiple primary cancers.
AB  - Cancer patients have a 20% higher risk of new primary cancer compared with the
      general population. Approximately one third of cancer survivors aged >60 years
      were diagnosed more than once with another cancer. As the number of cancer
      survivors and of older people increases, occurrence of multiple primary cancers
      is also likely to increase. An increasing interest from epidemiologic and
      clinical perspectives seems logical. This chapter begins with the risk pattern of
      multiple cancers in the population of a developed country with high survival
      rates. Multiple cancers comprise two or more primary cancers occurring in an
      individual that originate in a primary site or tissue and that are neither an
      extension, nor a recurrence or metastasis. Studies of multiple cancers have been
      mainly conducted in population-based settings, and more recently in clinical
      trials and case control studies leading to further understanding of risk factors
      for the development of multiple primary cancers. These factors include an
      inherited predisposition to cancer; the usual carcinogenic or cancer-promoting
      aspects of lifestyle, hormonal, and environmental factors; treatment of the
      previous primary cancer; and increased surveillance of cancer survivors. Finally,
      implication on research strategies and clinical practice are discussed, covering
      the whole range of epidemiologic approach.

PMID- 19109777
TI  - Cancer screenings, diagnostic technology evolution, and cancer control.
AB  - Screening should allow for the anticipation of cancer diagnosis at an earlier
      stage, when curative treatment is possible. Screening for cervical, large bowel,
      and breast cancer were shown to be effective in reducing mortality. The wide
      acceptance of the screening concept led to the wide diffusion also of screening
      of uncertain benefit against prostate cancer and skin melanoma. Diagnostic
      technologies are continuously evolving, and new tests are proposed to improve
      existing screenings or as screening tests for additional cancer sites (e.g., lung
      cancer). Cancer screening, however, is a complex and costly intervention that
      does not result only in benefits but also may cause harm. A major emerging
      problem of screening is overdiagnosis, or the detection of cases that would have
      not progressed to the symptomatic phase in the absence of screening. Thus, both
      experimental and observational evaluation studies are needed to reduce harm
      caused by screenings and to select effective interventions among many proposed
      innovations. Finally, the research of markers to assess the aggressive nature of
      screen-detected lesions is of great importance to improve screenings '
      harm/benefit ratio.

PMID- 19109778
TI  - Thriving for clues in variations seen in mortality and incidence of cancer:
      geographic patterns, temporal trends, and human population diversities in cancer
      incidence and mortality.
AB  - To address the diverse features of the cancer epidemic, scientists have
      continually been seeking out different aspects of the cancer problem from cell
      proliferation at the microenvironment of the cancerous cells to large-scale
      diversities and variations seen in the incidence of cancer and prevalence of
      exposure to potential or known carcinogens in as many global locations and as
      many occasions as possible. The variations of cancer occurrence in the three
      dimensions of place, time, and human population have been the pillar of
      hypothesis formation in understanding the diverse features of the cancer
      epidemic. The aim of this chapter is to address the methodologic issues
      pertaining to changing of cancer incidence and mortality in the three dimensions.
      For each dimension; a brief description of available information on the cancer
      incidence and mortality is presented, the sources of available data are
      introduced, the indicators to be used and their inter-pretabilities are
      addressed, and the use of new technologies pertaining to that dimension are
      discussed.

PMID- 19109780
TI  - Introduction to the use of regression models in epidemiology.
AB  - Regression modeling is one of the most important statistical techniques used in
      analytical epidemiology. By means of regression models the effect of one or
      several explanatory variables (e.g., exposures, subject characteristics, risk
      factors) on a response variable such as mortality or cancer can be investigated.
      From multiple regression models, adjusted effect estimates can be obtained that
      take the effect of potential confounders into account. Regression methods can be
      applied in all epidemiologic study designs so that they represent a universal
      tool for data analysis in epidemiology. Different kinds of regression models have
      been developed in dependence on the measurement scale of the response variable
      and the study design. The most important methods are linear regression for
      continuous outcomes, logistic regression for binary outcomes, Cox regression for
      time-to-event data, and Poisson regression for frequencies and rates. This
      chapter provides a nontechnical introduction to these regression models with
      illustrating examples from cancer research.

PMID- 19109779
TI  - Evaluation of environmental and personal susceptibility characteristics that
      modify genetic risks.
AB  - Study design in understanding gene-environment interaction plays a crucial role.
      Different study designs with their advantages and limitations are described in
      this chapter. Gene penetrance has been studied in several cancers, including
      breast and prostate cancer. Compared with high-penetrance genes, such as breast
      cancer (BRCA)1, BRCA2 in breast cancer, gene-environment interaction plays a
      major role in cancer development where low-penetrance genes are the major
      players. Genetic polymorphism is determined in low- and high-penetrance genes to
      identify cancer-related polymorphisms. The role of genetic and epigenetic factors
      in cancer development is discussed. Preventive approaches, especially in the
      epigenetic field, show promise. A discussion about different epidemiological
      methods with examples is provided.

PMID- 19109781
TI  - Proteomics and cancer epidemiology.
AB  - Profiling of differentially expressed proteins is perhaps the most important and
      useful approach in developing tools for risk assessment in a population,
      diagnostic screening, and therapeutics. Proteomic markers have potential for
      identifying individuals at high risk of developing cancer; however, these markers
      have not been extensively used in cancer epidemiologic studies. Several markers
      have to be clinically validated. In this chapter, methods used in proteomic
      analysis of clinical samples, challenges in the proteomics and cancer
      epidemiology, and their potential solutions are discussed.

PMID- 19109782
TI  - Different study designs in the epidemiology of cancer: case-control vs. cohort
      studies.
AB  - It is only since the 1950s that most of the epidemiology studies on cancer have
      been conducted. The principal study designs for epidemiologic study of cancer
      etiology are case-control and cohort studies. These study designs have
      complimentary roles and distinct advantages and disadvantages. This chapter
      provides historical perspectives, description of the traditional and variant
      designs of case-control and cohort studies, and the relative advantages and
      disadvantages of these study designs.

PMID- 19109783
TI  - Methods and approaches in using secondary data sources to study race and
      ethnicity factors.
AB  - Race and ethnicity are increasing used in cancer research to assess differences
      in cancer incidence and response to therapy. In this chapter, we discuss the
      measurement and methodologic issues that should be addressed to minimize bias and
      derive valid estimates when performing such assessments. These issues include 1)
      lack of national standards for race and ethnicity categories; 2) difficulty in
      comparing race and ethnic categories in longitudinal assessments; 3) broad
      categorization of race and ethnicity groups that do not provide adequate details
      for meaningful assessments; 4) inaccuracies in race and ethnicity data
      collection, and 5) confounding by socioeconomic and other factors.
      Recommendations for improving race and ethnicity data collection also are
      discussed.

PMID- 19109784
TI  - Statistical methods in cancer epidemiological studies.
AB  - In this chapter, we discuss statistical methods for various study designs that
      are commonly used in epidemiological research and particularly in cancer
      epidemiological research. After a brief review of basic concepts in
      epidemiological studies, statistical methods for case-control studies and cohort
      studies are discussed. Statistical methods for nested case-control and case
      cohort studies, which have been increasingly used in cancer epidemiology, also
      are discussed. This chapter is designed for cancer epidemiologists who understand
      basic statistical methods for commonly used epidemiological study designs and are
      able to initiate power and sample size calculations. Therefore, this chapter
      emphasizes newly developed statistical methods for epidemiological studies as
      well as study planning.

PMID- 19109785
TI  - Methods in cancer epigenetics and epidemiology.
AB  - Cancer cells are characterized by epigenetic dysregulation, including global
      genome hypomethylation, regional hypo- and hypermethylation, histone
      modifications, and disturbed genomic imprinting. These alterations can be used as
      markers in cancer epidemiology to assess risk as well as follow-up of the
      disease. Some of the methylation markers can be assayed on microarray chips on
      which a very small amount of sample is needed, and the assays are robust and the
      markers have high specificity and sensitivity. Implication of epigenetic markers
      in cancer detection, diagnosis, prognosis, control, and cancer epidemiology is
      discussed.

PMID- 19109786
TI  - Mitochondrial DNA polymorphism and risk of cancer.
AB  - ATP (energy production) production is not the only function of the mitochondria.
      Mitochondria perform multiple cellular functions. Among others, these functions
      include control of cell death, growth, development, integration of signals from
      mitochondria to nucleus and nucleus to mitochondria, and various metabolic
      pathways. Although defects in mitochondrial function are most commonly associated
      with bioenergetic deficiencies, our studies demonstrate that mitochondrial
      defects lead to genome instability in the nuclear DNA, resistance to apoptosis
      and induction of NADPH oxidase, a designated producer of reactive oxygen species.
      These transformations in cellular phenotype are known contributors to the
      development of tumors in humans. Consistent with the role of mitochondria in
      carcinogenesis, studies in the past few years have described an increased risk of
      cancers associated with specific mitochondrial DNA (mtDNA) polymorphism among
      various different haplogroups in human population. However, molecular mechanisms
      underlying increased risk of cancer due to specific mtDNA polymorphisms is
      currently lacking. It is likely that mtDNA polymorphisms in mitochondrial genes
      involved in electron transport chain and oxidative phosphorylation result in
      increased oxidative stress and hypermutagenesis of mitochondrial as well as
      nuclear DNA. We suggest that in studies relating to cancer epidemiology, the
      significance of a particular mtDNA polymorphism(s) should be analyzed together
      with other polymorphisms in mtDNA and in nuclear DNA.

PMID- 19109787
TI  - Polymorphisms of DNA repair genes: ADPRT, XRCC1, and XPD and cancer risk in
      genetic epidemiology.
AB  - Many studies have suggested that adenosine diphosphate ribosyl transferase
      (ADPRT), X-ray repair cross-complementing 1 (XRCC1), and xeroderma pigmentosum
      complementary group D (XPD) are three major DNA base excision repair (BER) genes
      and that they act interactively in stimulating and executing BER processes.
      Polymorphisms of these genes may influence the rate of gene transcription, the
      stability of the messenger RNA, or the quantity and activity of the resulting
      protein. Thus, the susceptibility or severity of several disorders is influenced
      by possession of specific alleles of polymorphic genes. So, it is plausible that
      variations and mutations in these genes affect DNA repair capacity in normal
      populations, and thus facilitate cancer development in normal or exposed
      individuals. To promote translation of scientific findings for potential clinical
      application of DNA repair function, we have searched publications relevant to
      molecular epidemiology studies of associations between single-nucleotide
      polymorphisms (SNPs) in the genes, and several frequent human cancer. We have
      focused on five particular polymorphisms as our starting point: the T-->C
      polymorphism (Val762Ala) in exon 17 of ADPRT, the novel transition at the
      promoter region (-77T-->C) of XRCC1, two common nonsynonymous polymorphisms
      (Arg194Trp and Arg399Gln), and the C-->A silent polymorphism (Arg156Arg) in exon
      6 of XPD. We review here the case-control studies examining whether these
      polymorphisms are correlated with reduced DNA repair efficiency, their influence
      on the development of different solid tumors, and their possible interactions
      with other genetic factors and environmental exposures.

PMID- 19109788
TI  - Risk factors and gene expression in esophageal cancer.
AB  - Esophageal cancer is a significant worldwide health problem because of its poor
      prognosis and high incidence in certain parts of the world. Tobacco smoke and
      alcohol consumption are significant risk factors for esophageal squamous cell
      carcinoma, whereas frequent gastroesophageal reflux and subsequent inflammatory
      reactions play a role in causing the adenocarcinoma. Esophageal carcinogenesis
      involves multiple genetic alterations. A large body of knowledge has been
      generated regarding molecular alterations associated with esophageal
      carcinogenesis. These alterations include aberrant cell cycle control, DNA
      repair, cellular enzymes, growth factor receptors, and nuclear receptors. This
      chapter reviews the most frequent gene alterations and their correlation with
      risk factors as well as the prevention strategies in esophageal cancer.

PMID- 19109790
TI  - Linking the Kaposi's sarcoma-associated herpesvirus (KSHV/HHV-8) to human
      malignancies.
AB  - In 1994, the Kaposi's sarcoma-associated herpesvirus (KSHV/HHV-8) was identified
      as the etiologic agent of Kaposi's sarcoma (KS). KSHV has since been associated
      with two additional malignancies: primary effusion lymphoma and multicentric
      Castleman's disease. In this chapter, we describe the current understanding of
      the pathogenesis, transmission, and prevalence of KSHV, and its association
      mainly with KS. We describe evidence demonstrating that KSHV is a causative agent
      for KS, and we present other factors that possibly contribute to the incidence of
      KS. We compare worldwide data on the prevalence of KS and of KSHV infection.
      Specific viral genes that may induce KS tumors or enable their growth also are
      described. Finally, we discuss the implications of the transmission modes and
      epidemiology of this virus on recommendations for KSHV screening of tissues and
      blood products before transplantation or transfusion.

PMID- 19109791
TI  - Cancer cohort consortium approach: cancer epidemiology in immunosuppressed
      groups.
AB  - Nearly 40 years have passed since the publication of the first report showing
      higher cancer risks in recipients of organ transplants. Thereafter, studies
      carried out in immunosuppressed persons have greatly expanded our knowledge on
      the spectrum of cancers associated with infections. Clinical investigations
      following the expanding practice of organ transplantation, and since the 1980s,
      studies on human immunodeficiency virus (HIV)-infected persons have thereafter
      confirmed and extended these early observations. The comparison of the spectrum
      of cancers seen in excess in these two groups of populations offers an original
      viewpoint into the association of immunosuppression and cancer. Combining
      longitudinal data from different cohorts of HIV-infected persons and of
      transplant recipients represents a further tool for better quantifying the
      spectrum of cancers associated with immunodepression. In this chapter, the use of
      this methodologic approach in southern Europe is illustrated and limitations are
      discussed.

PMID- 19109789
TI  - Single nucleotide polymorphisms in DNA repair genes and prostate cancer risk.
AB  - The specific causes of prostate cancer are not known. However, multiple etiologic
      factors, including genetic profile, metabolism of steroid hormones, nutrition,
      chronic inflammation, family history of prostate cancer, and environmental
      exposures are thought to play significant roles. Variations in exposure to these
      risk factors may explain interindividual differences in prostate cancer risk.
      However, regardless of the precise mechanism(s), a robust DNA repair capacity may
      mitigate any risks conferred by mutations from these risk factors. Numerous
      single nucleotide polymorphisms (SNPs) in DNA repair genes have been found, and
      studies of these SNPs and prostate cancer risk are critical to understanding the
      response of prostate cells to DNA damage. A few SNPs in DNA repair genes are
      associated with significantly increased risk of prostate cancer; however, in most
      cases, the effects are moderate and often depend upon interactions among the risk
      alleles of several genes in a pathway or with other environmental risk factors.
      This report reviews the published epidemiologic literature on the association of
      SNPs in genes involved in DNA repair pathways and prostate cancer risk.

PMID- 19109792
TI  - Do viruses cause breast cancer?
AB  - Because mouse mammary tumor virus (MMTV; the Bittner virus) is the proven cause
      of breast cancer in both field and experimental mice, similar viruses have long
      been suspects as a potential cause of human breast cancer. MMTV-like viral
      genetic material has been identified in human breast tumors, but there is no
      definitive evidence whether MMTV is causal and not merely an innocuous infection
      in humans. High-risk human papilloma viruses (HPVs), Epstein-Barr (EBV), and
      other viruses also have been identified in human breast tumors, but again there
      is no definitive evidence for a causal role. Any viral hypothesis as a cause of
      breast cancer must take into account the most striking epidemiologic feature of
      human breast cancer, the three- to sixfold differences in mortality and up to
      eightfold differences in incidence between some Asian and Western populations.
      These differences dramatically lessen to a two- to threefold difference within
      one or two generations of migration of females from low to high risk of breast
      cancer countries. In this chapter, a plausible explanation for these phenomena is
      offered; that is, the hypothesis that oncogenic viruses such as MMTV and high
      risk HPVs may initiate some breast cancers in most populations. Furthermore,
      dietary patterns are suggested to determine circulating sex hormone levels, which
      in turn promote the replication of the hormone-dependent viruses MMTV and HPV. In
      addition, diet and hormones promote growth of both normal and malignant cells.
      Finally, the hypothesis that migrants from low to high risk of breast cancer
      countries change their food consumption patterns is suggested, which leads to
      higher circulating hormone levels, which in turn promotes viral replication,
      which initiates breast oncogenesis, which is enhanced by sex and growth hormones.

PMID- 19109793
TI  - Epidemiology of Human Papilloma Virus (HPV) in Cervical Mucosa.
AB  - In a worldwide scenario, human papillomavirus (HPV) infection is the second
      leading cause of cancer-related morbidity and mortality among women due to its
      very close association with cervical cancer. More than 100 different types of HPV
      genotypes have been characterized to date. Among these, approximately 24 HPV
      genotypes specifically infect the genital and oral mucosal system. The mucosal
      HPVs are most frequently sexually transmitted, and they are responsible for the
      most common sexually transmitted diseases throughout the world. In a majority of
      the cases, oncogenic/nononcogenic HPV infections spontaneously clear by
      themselves without any medical intervention. However, a persistent and long-term
      HPV infection usually leads to cervical cancer, which remains difficult to treat.
      In recent years, advance understanding of the structure of HPV and its
      pathogenesis has led to a variety of new treatments to combat HPV-related
      diseases, including a Food and Drug Administration-approved HPV vaccine that is
      very effective in young women. To effectively use this HPV vaccine worldwide, a
      clear understanding of HPV genotypes in different geographical populations is
      imperative. In this chapter, we have focused briefly on HPV genotypes and HPV
      prevalence in the women of different geographical populations.

PMID- 19109794
TI  - Epigenetic targets in cancer epidemiology.
AB  - Recently, it has been shown that epigenetic changes are involved in early stages
      of tumorigenesis, and they may trigger the genetic events leading to tumor
      development. In cancer epidemiology, there are several epigenetic alterations
      involved, such as DNA hypermethylation, DNA hypomethylation, and chromatin
      modifications with critical roles in the initiation and progression of human
      neoplasms. This chapter discusses the hypermethylation profiles of several tumor
      types, including bladder, brain, breast, colorectal, ovarian, prostate, and other
      cancers as well as DNA hypomethylation phenomena together with the chromatin
      modifications and their role in the complex mechanism of epigenetic silencing.
      Moreover, the involvement of environmental exposures in cancer susceptibility is
      addressed. In conclusion, these epigenetic changes are important characteristics
      of human neoplasia, and a better understanding of these modifications and the
      link between these changes for each tumor type will be important in early
      diagnosis of cancer and cancer prevention.

PMID- 19109796
TI  - Hereditary breast and ovarian cancer syndrome : the impact of race on uptake of
      genetic counseling and testing.
AB  - Breast cancer is a significant cause of morbidity and mortality in the United
      States. Although breast cancer is more common among White American (WA) women,
      incidence rates are higher among young African American (AA) women. Approximately
      5-10% of all breast cancer can be accounted for by germline mutations in the
      breast cancer (BRCA)1 and BRCA2 genes responsible for hereditary breast and
      ovarian cancer (HBOC) syndrome. Although genetic counseling (GC) and genetic
      testing (GT) for HBOC have become widely accepted by the WA population, cancer
      genetic services are underused among AA. Many investigators have evaluated a wide
      spectrum of BRCA1 and BRCA2 mutations in the AA and African population with the
      possible identification of African founder mutations. Barriers to GC and GT
      include lack of knowledge and/or negative attitudes regarding genetics and
      genetics research, and concerns regarding the potential for racial
      discrimination. It is important for future research to focus on ways in which to
      eliminate barriers to GC and GT to alleviate disparity in the use of genetic
      services among high-risk AA women.

PMID- 19109795
TI  - Epidemiology of lung cancer prognosis: quantity and quality of life.
AB  - Primary lung cancer is very heterogeneous in its clinical presentation,
      histopathology, and treatment response; and like other diseases, the prognosis
      consists of two essential facets: survival and quality of life (QOL). Lung cancer
      survival is mostly determined by disease stage and treatment modality, and the 5
      Year survival rate has been in a plateau of 15% for three decades. QOL is focused
      on life aspects that are affected by health conditions and medical interventions;
      the balance of physical functioning and suffering from treatment side effects has
      long been a concern of care providers as well as patients. Obviously needed are
      easily measurable biologic markers to stratify patients before treatment for
      optimal results in survival and QOL and to monitor treatment responses and
      toxicities. Targeted therapies toward the mechanisms of tumor development,
      growth, and metastasis are promising and actively translated into clinical
      practice. Long-term lung cancer (LTLC) survivors are people who are alive 5 Years
      after the diagnosis. Knowledge about the health and QOL in LTLC survivors is
      limited because outcome research in lung cancer has been focused mainly on short
      term survival. The independent or combined effects of lung cancer treatment,
      aging, smoking and drinking, comorbid conditions, and psychosocial factors likely
      cause late effects, including organ malfunction, chronic fatigue, pain, or
      premature death among lung cancer survivors. New knowledge to be gained should
      help lung cancer survivors, their healthcare providers, and their caregivers by
      providing evidence for establishing clinical recommendations to enhance their
      long-term survival and health-related QOL.

PMID- 19109797
TI  - Prognostic significance of insulin-like growth factor II mRNA-binding protein 3
      expression in gastric adenocarcinoma.
AB  - BACKGROUND: Insulin-like growth factor II mRNA-binding protein (IMP) 3 is
      expressed in embryonic tissues and multiple cancers. The aim was to establish the
      prognostic value of IMP-3 expression in gastric adenocarcinoma. METHODS: IMP-3
      expression in resected gastric adenocarcinomas was analysed by
      immunohistochemistry. RESULTS: IMP-3 was expressed in 183 (58.1 per cent) of 315
      tumours. Expression was associated with older age (P < 0.001), larger tumour size
      (P = 0.009), deep tumour invasion (P < 0.001) and lymph node metastasis (P <
      0.001). IMP-3-positive tumours were associated with poorer 5-year survival than
      negative tumours at all stages (stage I, 82 versus 97 per cent; stage II, 55
      versus 78 per cent; stage III and IV, 11 versus 25 per cent; P = 0.005, P = 0.033
      and P = 0.036 respectively). Multivariable analysis identified IMP-3 (hazard
      ratio (HR) 1.93), depth of tumour invasion (HR 3.69, 9.77 and 10.69 for
      pathological tumour stage (pT) 2, pT3 and pT4 respectively versus pT1), and lymph
      node metastasis (HR 1.57, 3.29 and 3.40 for pathological node stage (pN) 1, pN2
      and pN3 respectively versus pN0) as independent prognostic factors. CONCLUSION:
      IMP-3 expression correlates with the metastatic potential of gastric
      adenocarcinoma and is an independent prognostic factor.

PMID- 19109798
TI  - Acute pancreatitis and the influence of socioeconomic deprivation.
AB  - BACKGROUND: A comprehensive epidemiological study of acute pancreatitis (AP)
      using reliable objective methods of patient identification with the inclusion of
      socioeconomic factors has not been reported previously. METHODS: The study
      included all patients with AP identified by raised serum amylase or lipase levels
      admitted to 18 hospitals over 6 months. Clinical records were reviewed to confirm
      the diagnosis, aetiology and outcome. Patients were stratified into quintiles of
      socioeconomic deprivation. Age-standardized incidence (ASI) and mortality were
      calculated. RESULTS: Clinical data were reviewed for all 963 identified patients.
      The ASI was 56.5 per 10(5) per annum, double the highest figure reported
      previously in the UK. Univariable logistic regression analysis showed a high ASI
      among older age groups (odds ratio (OR) 1.06 per year; P < 0.001) and in areas of
      high deprivation (OR 2.40 between least and most deprived; P < 0.001); the latter
      was predominantly related to alcoholic aetiology (OR 6.50 (95 per cent confidence
      interval 3.90 to 10.84)). CONCLUSION: The incidence of AP based on a highly
      sensitive method of case identification was higher than previously reported. A
      clear relationship was found between socioeconomic deprivation and incidence of
      AP, which was largely explained by a higher incidence of alcoholic aetiology.

PMID- 19109799
TI  - Liver dysfunction and sepsis determine operative mortality after liver resection.
AB  - BACKGROUND: Liver failure is the principal cause of death after hepatectomy. Its
      progression towards death and its relationship with sepsis are unclear. This
      study analysed predictors of mortality in patients with liver dysfunction and the
      role of sepsis in the death of these patients. METHODS: The study focused on
      patients with liver dysfunction, excluding those with vascular thrombosis, after
      liver resection at one of two centres between 1998 and 2006. RESULTS: Liver
      dysfunction occurred after 57 (4.5 per cent) of 1271 hepatectomies. Fifty-three
      patients without vascular thrombosis were included in the analysis, with a
      mortality rate of 23 per cent. Independent predictors of death were age (odds
      ratio (OR) 1.18 per year increase; P = 0.017), cirrhosis (OR 54.09; P = 0.004)
      and postoperative sepsis (OR 37.58; P = 0.005). Sepsis occurred in 15 patients
      (28 per cent), seven of whom died. Intestinal pathogens were isolated in 12
      patients with sepsis. The risk of sepsis was significantly increased in those
      with surgical complications (11 of 16 versus four of 37; P < 0.001). CONCLUSION:
      Sepsis plays a key role in the death of patients with liver dysfunction after
      hepatectomy. Early recognition and aggressive treatment of sepsis may reduce
      mortality.

PMID- 19109800
TI  - Dangerous halo after neoadjuvant chemotherapy and two-step hepatectomy for
      colorectal liver metastases.
AB  - BACKGROUND: Bilobar colorectal metastases are a therapeutic challenge and require
      a multidisciplinary approach. The aim of this study was to describe the clinical
      and histological outcomes of patients having neoadjuvant chemotherapy and two
      step hepatectomy with right portal vein occlusion for advanced bilateral
      colorectal metastases. METHODS: A series of 23 consecutive patients treated with
      curative intent according to a standardized multidisciplinary management protocol
      was reviewed. RESULTS: Of 23 patients, 22 completed the programme. There was no
      mortality and no Clavien grade III morbidity. Median survival from the start of
      treatment was 45 months, and 1-, 3- and 5-year Kaplan-Meier estimates were 95, 73
      and 27 per cent respectively. On histology at the first operation, ten patients
      had a dangerous halo of proliferating tumour cells infiltrating the surrounding
      liver parenchyma, of variable importance (six focal and four diffuse), regardless
      of the response to chemotherapy of the metastases. The dangerous halo increased
      in prevalence and importance (six focal and seven diffuse) between the first and
      second operation. CONCLUSION: Neoadjuvant chemotherapy followed by two-step
      hepatectomy with right portal vein occlusion is feasible, safe and may be
      advantageous to the patient. The appearance of a dangerous halo around the liver
      metastases may require adaptation of the surgical technique to decrease the risk
      of local recurrence.

PMID- 19109801
TI  - Validation of death and suicide recording on the THIN UK primary care database.
AB  - PURPOSE: Data from a cohort study were used to investigate death and cause of
      death (COD) recording on the THIN UK primary care database. METHODS: Subjects
      from 118 practices had a body mass index recorded, 2002-2003 (index date), no
      recent pregnancy or emotional event, or cancer. Coded and free text entries were
      searched for a COD for deaths dated < or = 485 days after index date. External
      documents were requested when date or COD were unclear, suicide was possible, and
      for a random sample of 40 patients with a COD identified. RESULTS: Five of 1399
      deaths dated within 1 year of the index date had not died (positive predictive
      value 99.6%) and 4 of 222 dated within 366-485 days had died during the year
      (sensitivity 99.7%). A database COD was identified for 887 (63.4%) with external
      documents received for 597 (92.8% requested). Of 40 compared with external
      sources, the underlying COD was on the database in 33 (82.5%), and could be
      identified as such in 26 (65%). The date was within 1 day of that on external
      documents in 504 (94.9%) with a date of death but 3 (5.7%) with only a transfer
      out of practice date. One of seven suicides was recorded as such. CONCLUSION: Any
      database record of death or its date is reliable, but transfer-out date is often
      later. Studies of COD or acute, potentially fatal conditions will miss cases
      unless a COD is obtained for all fatalities. Most suicides are not noted as such
      on the electronic record.

PMID- 19109802
TI  - Risk of acute myocardial infarction in patients treated with thiazolidinediones
      or other antidiabetic medications.
AB  - PURPOSE: Controversy surrounds the question whether thiazolidinediones (TZDs)
      increase the risk of acute myocardial infarction (AMI). This study examined risk
      of AMI in patients with type 2 diabetes mellitus (T2DM) who were taking TZDs or
      other antidiabetic medications. METHODS: Using a nested case-control design, a
      cohort of patients aged 18-84 years with T2DM and use of an oral antidiabetic
      medication or exenatide between January 2002 and June 2006 was identified. Cases
      of AMI were matched with up to four controls based on age, gender, health plan,
      geography, and diabetes therapy regimen. Over the 1-year pre-index period, TZD
      exposure was compared with no TZD exposure, after adjustment for potential
      confounders. RESULTS: Overall, 1681 cases were identified and matched with 6653
      controls. Compared with no TZD exposure, an increased risk of AMI was not
      observed among TZD exposed patients (adjusted OR 1.01; 95%CI, 0.85-1.20; adjusted
      p = 0.98). When exposure proximity to the event was examined, the risk of AMI was
      significantly increased with recent rosiglitazone exposure between 1 and 60 days
      prior to the case date (adjusted OR 1.69; 95%CI, 1.18-2.44; adjusted p = 0.045)
      and was not significantly increased with current or remote rosiglitazone exposure
      or current, recent, or remote pioglitazone exposure. CONCLUSION: TZD exposure did
      not increase the risk of AMI when exposure proximity was not considered. However,
      when evaluating exposure proximity to the event, the risk of AMI was increased
      with recent rosiglitazone exposure between 1 and 60 days prior to the case date.

PMID- 19109803
TI  - Three-dimensional ultrasound diagnosis of cleft palate: 'reverse face', 'flipped
      face' or 'oblique face'--which method is best?
AB  - OBJECTIVES: To compare the performance of three sonographic techniques, the
      'reverse-face', 'flipped-face' and 'oblique-face' methods, for visualizing the
      hard and soft palate in diagnosing cleft lip and palate (CLP). METHODS: A total
      of 60 fetuses (10 with CLP) with a gestational age ranging from 20 to 33 weeks
      were examined. We compared visualization of the secondary palate with the
      previously described reverse-face and flipped-face methods (the latter modified
      by us) and the oblique-face method developed by us using Oblique View imaging
      technology. RESULTS: Among the 10 fetuses with CLP the defect involved the lip,
      alveolus and secondary palate in seven, and the primary palate only in the
      remaining three. The upper lip and alveolar ridge were well visualized in all
      cases with all three methods. Involvement of the hard palate was diagnosed
      correctly in 71% (5/7) of the cases using the reverse-face view, in 86% (6/7)
      with the flipped-face view, and in 100% (7/7) with the oblique-face view; the
      hard palate was correctly found to be intact in 78%, 84% and 86%, respectively,
      of the 50 normal fetuses examined with each view. Involvement of the soft palate
      was diagnosed correctly in only one of the seven fetuses with defects of the
      secondary palate in flipped-face and oblique-face views, and was correctly
      considered intact in only 16% of normal fetuses in flipped-face view and in 26%
      in oblique-face images. CONCLUSIONS: Accurate visualization of the soft palate
      requires an excellent initially acquired volume, fluid between the fetal tongue
      and palate, and curving of the plane to follow the structure of the palate. The
      oblique-face or flipped-face views make it possible to visualize the soft palate
      well in selected cases.

PMID- 19109804
TI  - Using second-order generalized estimating equations to model heterogeneous
      intraclass correlation in cluster-randomized trials.
AB  - In cluster-randomized trials, it is commonly assumed that the magnitude of the
      correlation among subjects within a cluster is constant across clusters. However,
      the correlation may in fact be heterogeneous and depend on cluster
      characteristics. Accurate modeling of the correlation has the potential to
      improve inference. We use second-order generalized estimating equations to model
      heterogeneous correlation in cluster-randomized trials. Using simulation studies
      we show that accurate modeling of heterogeneous correlation can improve inference
      when the correlation is high or varies by cluster size. We apply the methods to a
      cluster-randomized trial of an intervention to promote breast cancer screening.

PMID- 19109805
TI  - Concomitant injuries are an important determinant of outcome of high-grade blunt
      hepatic trauma.
AB  - BACKGROUND: Little is known about the clinical importance of concomitant injuries
      in polytraumatized patients with high-grade blunt liver injury. A retrospective
      single-centre study was performed to investigate the safety of non-operative
      management of liver injury and the impact of concomitant intra- and extra
      abdominal injuries on clinical outcome. METHODS: Some 183 patients with blunt
      liver injury were admitted to Berne University Hospital, Switzerland, between
      January 2000 and December 2006. Grade 3-5 injuries were considered to be high
      grade. RESULTS: Immediate laparotomy was required by 35 patients (19.1 per cent),
      owing to extrahepatic intra-abdominal injury (splenic and vascular injuries,
      perforations) in 21 cases. The mortality rate was 16.9 per cent; 22 of the 31
      deaths were due to concomitant lesions. Of 81 patients with high-grade liver
      injury, 63 (78 per cent) were managed without surgery; liver-related and extra
      abdominal complication rates in these patients were 11 and 17 per cent
      respectively. Grades 4 and 5 liver injury were associated with hepatic-related
      and extra-abdominal complications. CONCLUSION: Concomitant injuries are a major
      determinant of outcome in patients with blunt hepatic injury and should be given
      high priority by trauma surgeons. An algorithm for the management of blunt liver
      injury is proposed.

PMID- 19109806
TI  - Magnetic resonance imaging and the acute abdomen (Br J Surg 2008; 95: 1193-1194).

PMID- 19109808
TI  - Laparoscopic peritoneal lavage for generalized peritonitis due to perforated
      diverticulitis (Br J Surg 2008; 95: 97-101).

PMID- 19109809
TI  - Comparison of various measures for assessing medication refill adherence using
      prescription data.
AB  - BACKGROUND: Several measures using prescription data have been developed for
      estimating medication refill adherence. Few studies have made direct comparisons,
      and little is known about the accuracy of these measures in patients on a
      multiple-drug regimen. PURPOSE: To compare different calculation methods using
      prescription data for assessing refill adherence. METHOD: An observational cohort
      study among type 2 diabetes patients was conducted. Adherence to oral glucose
      lowering, antihypertensive and lipid-lowering medication was assessed for 2004.
      We calculated medication possession ratios in a flexible period (MPRF), per
      calendar year (MPRY) and gaps between refills (GAP) at drug class and therapeutic
      level. Individual review of drug prescription profiles was conducted to validate
      identified cases of suboptimal refill adherence. Differences in Area Under the
      Curve (AUC) of ROC-curves were calculated to compare the methods. RESULTS: Of the
      3877 patients, 2969 (77%) patients received oral glucose-lowering medication,
      2715 (70%) antihypertensives and 1797 (46%) lipid-lowering medication. Using
      cutoffs for MPR < 80% and GAP > 30 days, overall rates of suboptimal adherence
      for these drug classes were 32, 35 and 23% respectively. AUC for measures
      calculated at drug class level (range 0.85-0.90) were significantly larger than
      those calculated at therapeutic level (0.72-0.90). For oral glucose-regulating
      medication and antihypertensives, AUCs were largest for the MPRY and GAP measures
      (0.87-0.88). For lipid-lowering medication, the AUC was largest for the GAP
      measure (0.90). CONCLUSIONS: Differences between adherence measures were small
      and favoured calculation on drug class level. For multiple drug use, both MPRY
      and GAP were good measures for identifying suboptimal refill adherence.

PMID- 19109810
TI  - Robust fitting for neuroreceptor mapping.
AB  - Among many other uses, positron emission tomography (PET) can be used in studies
      to estimate the density of a neuroreceptor at each location throughout the brain
      by measuring the concentration of a radiotracer over time and modeling its
      kinetics. There are a variety of kinetic models in common usage and these
      typically rely on nonlinear least-squares (LS) algorithms for parameter
      estimation. However, PET data often contain artifacts (such as uncorrected head
      motion) and so the assumptions on which the LS methods are based may be violated.
      Quantile regression (QR) provides a robust alternative to LS methods and has been
      used successfully in many applications. We consider fitting various kinetic
      models to PET data using QR and study the relative performance of the methods via
      simulation. A data adaptive method for choosing between LS and QR is proposed and
      the performance of this method is also studied.

PMID- 19109812
TI  - Long-term health-related quality of life following surgery for oesophageal cancer
      (Br J Surg 2008; 95: 1121-1126).

PMID- 19109814
TI  - Bacterial artificial chromosome array-based comparative genomic hybridization
      using paired formalin-fixed, paraffin-embedded and fresh frozen tissue specimens
      in multiple myeloma.
AB  - BACKGROUND: Multiple myeloma (MM) is a neoplasm of malignant plasma cells that
      often harbors many chromosomal aberrations. Currently, fresh frozen tissues (FT)
      are considered the most reliable for molecular genetic analysis; however,
      formalin-fixed, paraffin-embedded (FFPE) tissues are easily retrievable. Compared
      with conventional cytogenetics, bacterial artificial chromosome (BAC) array
      comparative genomic hybridization (CGH) allows more sensitive detection of
      chromosomal abnormalities. METHODS: The authors analyzed 7 paired FT and FFPE
      samples of bone marrow aspirate materials obtained from patients with MM in
      parallel to determine the efficacy of BAC array-CGH using FFPE. RESULTS: Thirty
      four aberrations were identified, including 29 that were observed in both sample
      types, yielding 85% concordance. Nonrandom anomalies, including gains on 7q, 9q,
      15q, and 19p and losses on 8p and 13q, were observed in paired samples from at
      least 2 patients. To verify these results, fluorescence in situ hybridization
      (FISH) was performed using probes specific for 7q and 15q, and gains were
      observed in the 4 samples that were examined. Furthermore, 1 of 3 samples from
      patients who had monoclonal gammopathy of undetermined significance that were
      tested also carried gain on 7q, suggesting that this aberration may be an early
      transforming event. CONCLUSIONS: The current results indicated that BAC array-CGH
      can be effective using FFPE samples and is a sensitive method for the
      identification of nonrandom chromosomal aberrations in MM.

PMID- 19109815
TI  - Survival of distinct Asian groups among colorectal cancer cases in California.
AB  - BACKGROUND: It has been reported that Asian ethnicity confers a survival benefit
      in colorectal cancer (CRC) compared with other ethnicities, but it is not known
      if this is limited to specific Asian subsets. In the current study, the authors
      attempted to determine differences using data from the large, population-based
      California Cancer Registry (CCR). METHODS: The authors conducted a case-only
      analysis of CCR data (1994-2003), including descriptive analysis of relevant
      clinical variables. Overall survival univariate analyses were conducted using the
      Kaplan-Meier method. Multivariate survival analyses were performed using Cox
      proportional hazards ratios (HR). RESULTS: The 61,494 incident cases of colon and
      24,350 incident cases of rectal cancer analyzed included 1905 Chinese, 1162
      Filipino, 414 Vietnamese, 391 Korean, 1091 Japanese, 148 Asian Indian, and 77,554
      Caucasians. After adjustment for age, sex, grade, histology, site within the
      colon, stage of disease, insurance status, socioeconomic status (SES), and
      therapy, Filipino (colon: HR, 0.85; 95% confidence interval [95% CI], 0.76-0.95)
      (rectum: HR, 0.82; 95% CI, 0.71-0.94) and Chinese ethnicity (colon: HR, 0.90; 95%
      CI, 0.92-0.98) had significantly decreased risk of death compared with
      Caucasians. Sigmoid lesions were independently associated with improved survival
      among all cases (HR, 0.92; 95% CI, 0.88-0.95) (referent group were proximal and
      transverse lesions), and among Asian-only cases in separate analysis (HR, 0.78;
      95% CI, 0.70-0.87). CONCLUSIONS: Although survival after CRC diagnosis is
      improved for Asians in general, significant survival differences are observed
      only in specific Asian subsets. Data from the current study suggest that survival
      among Asians is less affected by SES or treatment disparities, and may be because
      of biologic factors.

PMID- 19109817
TI  - Hyperthermia-treated mesenchymal stem cells exert antitumor effects on human
      carcinoma cell line.
AB  - BACKGROUND: Mesenchymal stem cells (MSCs) possess the potential for
      differentiation into multilineages. MSCs have been reported to play a role as
      precursors for tumor stroma in providing a favorable environment for tumor
      progression. Hyperthermia destroys cancer cells by raising the temperature of
      tumor-loaded tissue to 40 degrees C to 43 degrees C and causes indirect
      sensitizing effects when combined with chemo- and/or radiotherapy. However, how
      hyperthermia affects the tumor-supportive stroma is unknown. Here, the authors
      investigated the effects of hyperthermia-treated MSCs, from different sources, on
      the human ovarian cancer cell line SK-OV-3. METHODS: MSCs from adipose tissue and
      amniotic fluid were untreated or heat-treated (HS-MSCs). The culture supernatant
      of each treatment group was collected and transferred to the SK-OV-3 cells.
      RESULTS: The morphological analysis and cell proliferation assay showed a reduced
      viability of the tumor cells in the conditioned medium with the HS-MSCs. Further
      investigations revealed that the conditioned medium of the HS-MSCs induced a
      higher nuclear condensation and a greater number of sub-G1 cells among the tumor
      cells. Analysis of the mRNA expression demonstrated that the conditioned medium
      of the HS-MSCs induced up-regulation or down-regulation of several tumor
      associated molecules. Finally, the cytokine array of each conditioned medium
      showed that angiogenin, insulin-like growth factor binding protein 4,
      neurotrophin 3, and chemokine (C-C motif) ligand 18 are involved as main factors.
      CONCLUSIONS: This study showed that the conditioned medium of the HS-MSCs exerted
      a suppressive effect on tumor progression and malignancy, suggesting that
      hyperthermia enables tumor stromal cells to provide a sensitizing environment for
      tumor cells to undergo cell death.

PMID- 19109816
TI  - Microsatellite instability and DNA ploidy in colorectal cancer: potential
      implications for patients undergoing systematic surveillance after resection.
AB  - BACKGROUND: Appropriate stratification tools for targeted surveillance after
      resection for colorectal cancer (CRC) are lacking. The objective of the current
      study was to investigate the effect of microsatellite instability (MSI) and DNA
      ploidy on surveillance after surgery. METHODS: The authors evaluated 186
      consecutive, population-based patients with stage I through III CRC who underwent
      surgery with curative intent and who entered a systematic surveillance program.
      MSI was analyzed with polymerase chain reaction for 5 known quasimonomorphic
      markers (BAT-26, BAT-25, NR-21, NR-24, and NR-27), and DNA ploidy was analyzed
      with automated cytometry. Recurrence, recurrence-free survival (RFS), and disease
      specific survival (DSS) were evaluated by univariate and multivariate statistical
      tests. RESULTS: Patients with MSI (20%) were significantly younger than patients
      without MSI (median age, 61 years vs 67 years; P=.016). Proximal location
      (adjusted odds ratio [AOR], 5.4; 95% confidence interval [95% CI], 2.1-14.1
      [P=.001]), large tumor size (>or=5 cm: AOR, 3.5; 95% CI, 1.3-9.6 [P=.015]), and
      poor tumor differentiation (AOR, 6.6; 95% CI, 2-21.8 [P=.002]) were associated
      with MSI. MSI conveyed an increased risk for locoregional recurrence (OR, 2.9;
      95% CI, 1.2-7 [P=.016]), with a trend toward a shorter time to recurrence
      (P=.060). Neither MSI status nor DNA ploidy predicted distant metastasis, RFS, or
      DSS. Lymph node status was the best predictor of distant spread (AOR, 3.9; 95%
      CI, 2-7.9 [P<.001]) and DSS (hazard ratio, 4.9; 95% CI, 2.6-9 [P<.001]).
      CONCLUSIONS: Patients who had microsatellite instable tumors were at increased
      risk for locoregional recurrence, whereas lymph node status was the best
      predictor of distant metastasis. Clinical surveillance and choice of modality
      (ie, endoscopy vs radiologic imaging) may be improved when patients are
      stratified according to these cancer features.

PMID- 19109818
TI  - Radiosurgical treatment of vestibular schwannomas in patients with
      neurofibromatosis type 2: tumor control and hearing preservation.
AB  - BACKGROUND: The radiosurgical treatment of vestibular schwannomas in patients
      with neurofibromatosis type 2 (NF2) is controversial. The authors investigated
      the radiologically proven tumor control rate after gamma knife radiosurgery. The
      factors that affect tumor control and serviceable hearing preservation were
      analyzed. METHODS: Thirty-six lesions in 30 patients were included. The median
      lengths of the clinical and radiologic follow-ups were 48.5 months and 36.5
      months, respectively. The median tumor volume was 3.2 cm3. The mean marginal dose
      was 12.1 grays (Gy) (range, 8-14 Gy) at an isodose line of 50%+/-0.6%. The Kaplan
      Meier method and Cox proportional hazards model were used for the statistical
      analyses. RESULTS: The actuarial tumor control rate was 81%, 74%, and 66%,
      respectively, in the first, second, and fifth years. Five tumors required a
      salvage surgery because of tumor control failure. A low marginal dose and a young
      age at radiosurgery were associated with poor tumor control. Of the 16 tumors
      with which ipsilateral hearing was serviceable, the actuarial serviceable hearing
      preservation rates were 50%, 45%, and 33%, respectively, in the first, second,
      and fifth years. Better ipsilateral hearing (Gardner-Robertson grade 1, compared
      with grade 2) at the time of radiosurgery was associated with significantly
      greater serviceable hearing preservation. CONCLUSIONS: Gamma knife radiosurgery
      for vestibular schwannomas in NF2 patients provided 5-year tumor control in
      approximately two-thirds of patients and preserved serviceable hearing in
      approximately one-third. The rates of other cranial nerve deficits were low, and
      no secondary malignancy was observed. Radiosurgery should be included in
      treatment options for NF2 patients.

PMID- 19109819
TI  - Fifty years of cancer in an American Indian population.
AB  - BACKGROUND: A clear understanding of cancer patterns among American Indian tribal
      groups has been complicated by a variety of issues. A retrospective cohort study
      design was applied to a Seneca Nation of Indians (SNI) cohort for the period from
      1955 through 2004. METHODS: Incident cancers were identified through a computer
      match with the New York State Cancer Registry. Standardized incidence ratios
      (SIRs) and 95% confidence intervals were calculated for the overall interval as
      well as for each of the 5 10-year intervals. The SNI cohort consisted of 3935 men
      and 4193 women with a total of 120,403 person-years. RESULTS: Significant
      deficits in cancer incidence were noted among men for all sites combined (SIR,
      69), and for lung (SIR, 59), prostate (SIR, 54), urinary bladder (SIR, 8), and
      Hodgkin lymphoma (SIR, 0); no cancer sites were identified with significantly
      elevated incidence. Women demonstrated significantly reduced cancer incidence for
      all sites combined (SIR, 70) and for breast (SIR, 39), colorectal (SIR, 72),
      ovary (SIR, 37), uterus (SIR, 42), bladder (SIR, 20), pancreas (SIR, 10), and non
      Hodgkin lymphoma (SIR, 39); elevated incidence was noted for cancers of the lung
      (SIR, 139) and liver (SIR, 405). CONCLUSIONS: To the authors' knowledge, the
      current study represents the most comprehensive investigation to date of cancer
      patterns among an American Indian tribal group and provides insights for the
      development of tribal cancer control programming.

PMID- 19109820
TI  - Leptomeningeal carcinomatosis: prognostic implications of clinical and
      cerebrospinal fluid features.
AB  - BACKGROUND: Leptomeningeal carcinomatosis (LC) represents a devastating
      complication of systemic cancer, and patients with LC have a dismal prognosis and
      increased mortality. The few studies that have focused on the evaluation of
      prognostic factors in patients with LC have resulted in contradictory results.
      Thus, the treatment of LC remains controversial, and no straightforward
      guidelines exist in the literature. The objective of the current study was to
      identify prognostic markers related to LC survival to better select patients who
      are eligible for intensive treatment. METHODS: Seventy patients who had a
      diagnosis of LC were reviewed, and clinical data, cerebrospinal fluid (CSF)
      parameters, tumor-related characteristics, and treatment information were
      registered. The impact of single parameters on overall survival was determined by
      both univariate and multivariate analyses. RESULTS: The multivariate analysis
      revealed that Radiation Therapy Oncology Group score<or=2 (P=.028), a glucose
      level in CSF>or=2.7 mmol/L (P=.001), the presence of infratentorial symptoms at
      onset (P=.026), and intrathecal treatment (P<.001) were associated independently
      with longer overall survival in patients with LC. In addition, the same clinical
      factors also predicted response to treatment in such patients. CONCLUSIONS: The
      predictive factors for patients with LC that were identified in this study could
      help to better select patients who are more likely to benefit from chemotherapy.

PMID- 19109821
TI  - Prophylactic mastectomy and the timing of breast reconstruction.

PMID- 19109823
TI  - Clostridium difficile infection and surgery.

PMID- 19109822
TI  - The persisting challenge of selective and specific proteasome inhibition.
AB  - Since the discovery of the proteasome and its structure elucidation intensive
      research programs in academic institutions and pharmaceutical industries led to
      identification of a wide spectrum of synthetic and natural small proteasomal
      inhibitors. Activity studies with these small molecules helped to deeply
      understand the complex biochemical organization and functioning of the
      proteasome. The new structural and biochemical insights placed the proteasome as
      an important anti-cancer drug target, as revealed by the dipeptide boronate
      proteasome inhibitor, bortezomib, which is currently used for treatment of
      multiple myeloma. Serious side effects and partial cell resistance against
      bortezomib demand creation and discovery of new improved generations of more
      specific and potent proteasomal inhibitors.

PMID- 19109825
TI  - Development and validation of a model for prediction of mortality in patients
      with acute burn injury.
AB  - BACKGROUND: The objective was to develop a user-friendly model to predict the
      probability of death from acute burns soon after injury, based on burned surface
      area, age and presence of inhalation injury. METHODS: This population-based
      cohort study included all burned patients admitted to one of the six Belgian burn
      centres. Data from 1999 to 2003 (5246 patients) were used to develop a mortality
      prediction model, and data from 2004 (981 patients) were used for validation.
      RESULTS: Mortality in the derivation cohort was 4.6 per cent. A mortality score
      (0-10 points) was devised: 0-4 points according to the percentage of burned
      surface area (less than 20, 20-39, 40-59, 60-79 or at least 80 per cent), 0-3
      points according to age (under 50, 50-64, 65-79 or at least 80 years) and 3
      points for the presence of an inhalation injury. Mortality in the validation
      cohort was 4.3 per cent. The model predicted 40 deaths, and 42 deaths were
      observed (P = 0.950). Receiver-operator characteristic curve analysis of the
      model for prediction of mortality demonstrated an area under the curve of 0.94
      (95 per cent confidence interval 0.90 to 0.97). CONCLUSION: An accurate model was
      developed to predict the probability of death from acute burn injury based on
      simple and objective clinical criteria.

PMID- 19109827
TI  - Membrane androgen receptor activation in prostate and breast tumor cells:
      molecular signaling and clinical impact.
AB  - In recent years, membrane androgen receptors (mARs) have been identified in
      prostate and breast tumor cells, and their activation by specific mAR ligands was
      linked to the regulation of crucial cell responses, such as cell growth,
      motility, and apoptosis. Analysis of the molecular signals triggered by mAR in
      the presence of anti-androgens has clearly differentiated mAR-dependent
      biological actions from those induced by the activation of the classical
      intracellular androgen receptors (iARs). In this review, we summarize the
      specific cellular events attributed to mAR activation and the experimental
      results on distinct non-genomic signaling cascades operating in various tumor
      cells independently of the iAR. Furthermore, we discuss the crucial role of actin
      cytoskeleton organization and signaling in mediating mAR responses. Finally, we
      assess the clinical impact of the reported mAR-induced apoptotic regression of
      prostate cancer cells both in vitro and in vivo and discuss the potential role of
      mAR as a novel therapeutic target.

PMID- 19109828
TI  - Catalytic peroxidation of nitrogen monoxide and peroxynitrite by globins.
AB  - Globins are generally considered as carriers of diatomic gaseous ligands (e.g.,
      O(2) and NO) in metazoa. Recently, the (pseudo-)enzymatic activity of globins
      towards reactive nitrogen and oxygen species has been elucidated. In particular,
      some globins (e.g., hemoglobin and myoglobin) catalyze the enzymatic scavenging
      of NO and peroxynitrite in the presence of H(2)O(2). Indeed, H(2)O(2) oxidizes
      some globins leading to the formation of water and of the heme-protein ferryl
      derivative, which, in turn, oxidizes NO and peroxynitrite leading to the
      formation of the globin ferric species, NO(2)(-), and NO(3)(-). Here, we
      hypothesize that NO, peroxynitrite, and H(2)O(2) are co-substrates for the
      peroxidase activity of some globins, this catalytic activity was reported in 1900
      for the first time, even though the substrates have never been identified firmly
      up to now.

PMID- 19109829
TI  - siRNA-targeted COL8A1 inhibits proliferation, reduces invasion and enhances
      sensitivity to D-limonence treatment in hepatocarcinoma cells.
AB  - The COL8A1 (collagen type VIII, alpha-1) gene, which encodes the alpha 1 chain of
      collagen, type VIII, may modulate migration, proliferation and adherence of
      various cells. Only very sparse information exists on COL8A1 expression in
      hepatocarcinoma. To investigate the possible role of COL8A1 in the mouse
      hepatocarcinoma cell line Hca-F with highly metastatic potential in the lymph
      nodes, we used an RNA interference (RNAi) approach to silence COL8A1 expression.
      The results showed that a small interfering RNA (siRNA) targeted against COL8A1
      significantly impeded Hca-F cells proliferation and colony formation in soft
      agar. This reduction of COL8A1 expression also led to the decreased invasion of
      Hca-F cells dramatically in vitro. Furthermore, the downregulation of COL8A1
      expression also sensitized cells to the action of D-limonene. These data together
      provide insights into the function of COL8A1 and suggest that COL8A1 might
      represent a new potential target for gene therapy in hepatocarcinoma.

PMID- 19109831
TI  - The validity of EQ-5D US preference weights in liver transplant candidates and
      recipients.
AB  - Health utility instruments assess patients' valuation of specific health states,
      which can be converted to quality-adjusted life years for cost-utility analysis.
      Data from the EQ-5D, a generic health-related quality of life questionnaire from
      EuroQoL, can be reported as 5 health status scores or as a single health
      preference weight (HPW). US population-based HPWs were published by Shaw and
      colleagues in 2005 (Med Care 2005;43:203-220). Our aim was to test the validity
      of US EQ-5D HPWs and health status scores in liver transplant patients. EQ-5D
      scores were converted to HPWs with Shaw et al.'s model. Data were stratified by
      measurement period: pretransplant period, early posttransplant period (< or =12
      months), intermediate posttransplant period (13-36 months), and late
      posttransplant period (>36 months). EQ-5D scores were compared to specific,
      hypothesized Short Form 36 Health Survey, Center for Epidemiologic Studies
      Depression Scale, and Beck Anxiety Inventory scores that were identified a priori
      on the basis of construct similarity. Criterion-related and construct validity
      were tested with nonparametric methods. Two hundred eighty-five adults
      participated (113 in the pretransplant period, 60 in the early posttransplant
      period, 47 in the intermediate posttransplant period, and 65 in the late
      posttransplant period), and follow-up averaged 36 +/- 36 months. Eighty-one
      percent of the hypothesized relationships between EQ-5D and gold-standard scales
      were strong (r > or = |0.5|, P < 0.001), and the remainder were moderate (r >
      |0.3|, P < 0.001). Differences between pretransplant and posttransplant EQ-5D
      HPWs were statistically significant. In conclusion, EQ-5D dimensions and the
      health utility index generated from Shaw's US population preference weights
      demonstrated criterion-related and construct validity in liver transplant
      patients. It is a valid instrument for cost-utility analysis in this setting.

PMID- 19109832
TI  - Intraoperative renal support during liver transplantation.
AB  - Acute kidney injury (AKI) is common in liver failure prior to orthotopic liver
      transplantation (OLT) and may complicate the intraoperative course. We describe
      the logistics of intraoperative continuous renal replacement therapy (CRRT)
      during OLT and the associated clinical outcomes. We performed a retrospective
      review of adult patients (age > 18 years) receiving intraoperative CRRT during
      OLT at the University of Alberta Hospital between January 1, 1996 and December
      31, 2005. Demographic, detailed clinical, and perioperative data, physiologic and
      laboratory measures, details of renal replacement therapy (RRT) provided, and
      data on renal recovery and survival were ascertained. Of 636 OLTs, 41 (6.4%)
      received intraoperative CRRT. The most common indications for OLT in these
      patients were hepatitis C (34.2%) and alcoholic (29.3%) cirrhosis. The median
      [interquartile range (IQR)] Model for End-Stage Liver Disease score was 38 (31
      43), and 90.2% were classified as Child-Pugh class C. Preoperatively, 70% were in
      the intensive care unit, 58.5% were mechanically ventilated, and 48.7% required
      vasopressor support. The median (IQR) duration of intraoperative CRRT was 258
      (189-390) minutes, representing 57% of the total operative time. Filter circuit
      clotting occurred in 40% but was not associated with a shorter CRRT duration (P =
      0.41). No other complications were described. CRRT allowed an even or negative
      intraoperative fluid balance in 92.7%. CRRT was continued in 78% after OLT for a
      median (IQR) of 5 (3-11) days. Of these, 24 (75%) were transitioned to
      intermittent hemodialysis for a median (IQR) of 15 (4-39) days. Survival was
      97.6% at 1 month and 75.6% at 1 year. Renal recovery to RRT independence occurred
      in 100% of survivors by 1 year; however, the mean (standard deviation) estimated
      glomerular filtration rate (eGFR) was 54.7 (19.1) mL/minute/m(2), with 62.1%
      having an eGFR < 60 mL/minute/m(2). In conclusion, our data suggest that
      intraoperative CRRT during OLT is achievable and safe. Intraoperative CRRT may be
      a valuable adjuvant therapy for those with preoperative AKI. Additional
      investigations are warranted.

PMID- 19109833
TI  - Health-related quality of life and employment status of liver transplant
      patients.
AB  - Health-related quality of life (HRQoL) is one preferable outcome measure of
      medical interventions such as liver transplantation (LT). The aim of this study
      was to compare HRQoL of LT patients with that of the general population and to
      assess the employment status of LT patients. HRQoL was measured with the 15D
      instrument, a validated, non-disease-specific, 15-dimensional, self-administered
      HRQoL instrument. The questionnaire was sent to all adult LT patients in Finland
      (401 patients) alive in June 2007. The response rate was 89% (353 patients). The
      results were compared to those of 6050 age-standardized and gender-standardized
      controls from the general population. LT patients (mean age, 55 years; range, 20
      82) had slightly worse HRQoL scores than the general population (mean 15D score,
      0.889 versus 0.907; P < 0.002). Survival time and retransplantation did not
      affect HRQoL significantly in age-adjusted and gender-adjusted analyses. HRQoL
      decreased with increasing age (P < 0.0001). Patients transplanted for acute liver
      failure (ALF) or chronic liver disease (CLD) had significantly worse HRQoL than
      the general population (P = 0.014 and P = 0.040). Forty-four percent of working
      age patients were employed at the time of the study. Persons that were employed
      had significantly better HRQoL than those unemployed (15D scores, 0.934 versus
      0.859; P < 0.0001). Eighty-seven percent of patients experienced improved working
      capacity after LT. Early retirement was the most common cause of unemployment
      (56% of unemployed patients), and those patients presented with worse HRQoL than
      patients unemployed for other reasons. In conclusion, HRQoL of LT patients is
      very close to that of the general population. Older age, CLD, and ALF impair
      HRQoL. Employment is an indicator of HRQoL.

PMID- 19109834
TI  - Long-term antiviral therapy for recurrent hepatitis C after liver transplantation
      in nonresponders: biochemical, virological, and histological impact.
AB  - More than 50% of patients with a recurrent posttransplant hepatitis C virus
      infection fail to respond to antiviral treatment. The aim of this study was to
      evaluate the interest of a long-term antiviral treatment maintained for more than
      48 weeks. Seventy treated patients, with a histological follow-up > 1 year, were
      enrolled in this observational, retrospective study. The duration of antiviral
      treatment, tolerance, and occurrence of virological, biochemical, and
      histological responses were recorded. Thirty-two patients were nonresponders
      after 48 weeks of treatment. Combined antiviral therapy was maintained for >12
      months in 26 and for >18 months in 21. Twelve patients had to discontinue their
      treatment. At 48 weeks, the rates of virological response and sustained
      virological response were 37% and 24.3%, respectively; at the end of the follow
      up, they were 48.5% and 35.7%. Virological response was significantly associated
      with a higher incidence of biochemical and histological response, regardless of
      its time of occurrence (before or after 6 months). Even in the absence of
      virological response, the rate of progression of fibrosis was significantly
      slowed in patients treated for more than 6 months. Our results show the
      feasibility, safety, and efficacy of long-term antiviral therapy in nonresponder
      patients with a recurrent posttransplant hepatitis C virus infection.

PMID- 19109835
TI  - Two different methods for donor hepatic transection: cavitron ultrasonic surgical
      aspirator with bipolar cautery versus cavitron ultrasonic surgical aspirator with
      radiofrequency coagulator-A randomized controlled trial.
AB  - The aim of this study was to compare the Cavitron ultrasonic surgical aspirator
      (CUSA) with bipolar cautery (BP) to CUSA with a radiofrequency coagulator
      [TissueLink (TL)] in terms of efficacy and safety for hepatic transection in
      living donor liver transplantation. Twenty-four living liver donors (n = 12 for
      each group) were randomized to undergo hepatic transection using CUSA with BP or
      CUSA with TL. Blood loss during parenchymal transection and speed of transection
      were the primary endpoints, whereas the degree of postoperative liver injury and
      morbidity were secondary endpoints. Median blood loss during liver transection
      was significantly lower in the TL group than in the BP group (195.2 +/- 84.5
      versus 343.3 +/- 198.4 mL; P = 0.023), and liver transection was significantly
      faster in the TL group than in the BP group (0.7 +/- 0.2 versus 0.5 +/- 0.2
      cm(2)/minute; P = 0.048). Significantly fewer ties were required during liver
      transection in the TL group than in the BP group (15.8 +/- 4.8 versus 22.8 +/-
      7.9 ties; P = 0.023). The morbidity rates were similar for the 2 groups. In
      conclusion, CUSA with TL is superior to CUSA with BP for donor hepatectomy in
      terms of blood loss and speed of transection with no increase in morbidity.

PMID- 19109836
TI  - Impact of the donor liver with steatosis in patients with hepatitis C virus: not
      so FAst.

PMID- 19109837
TI  - Side-to-side cavocavostomy with an endovascular stapler: Rescue technique for
      severe hepatic vein and/or inferior vena cava outflow obstruction after liver
      transplantation using the piggyback technique.
AB  - Venous outflow obstruction is a rare but potentially lethal complication after
      orthotopic liver transplantation (OLT) with the "piggyback" technique.
      Therapeutic options include angioplasty with or without stent placement, surgical
      reconstruction of the venous anastomosis, and retransplantation. Surgical options
      are technically very challenging and the outcomes discouraging. We describe here
      two cases of venous outflow obstruction in recipients of piggyback liver grafts,
      one involving both the vena cava and hepatic veins and the other affecting only
      hepatic vein outflow. Both patients were treated successfully with side-to-side
      cavo-cavostomy using an endovascular (endo-GIA) stapler. This novel technique is
      fast and effective in resolving the outflow obstruction.

PMID- 19109838
TI  - Hepatocyte transplantation in animal models.
AB  - More than 30 years after the first hepatocyte transplant to treat the Gunn rat,
      the animal model for Crigler-Najjar syndrome, there are still a number of
      impediments to hepatocyte transplantation. Numerous animal models are still used
      in work aimed at improving hepatocyte engraftment and/or long-term function.
      Although other cell sources, particularly hepatic and extrahepatic stem cells,
      are being explored, adult hepatocytes remain the cells of choice for the
      treatment of liver diseases by cell therapy. In recent years, diverse approaches
      have been developed in various animal models to enhance hepatocyte transduction
      and amplification in vitro and cell engraftment and functionality in vivo. They
      have led to significant progress in hepatocyte transplantation for the treatment
      of patients with metabolic diseases and for bridging patients with acute injury
      until their own livers regenerate. This review presents and considers the results
      of this work with a special emphasis on procedures that might be clinically
      applicable.

PMID- 19109839
TI  - Abdominal drains in liver transplantation: useful tool or useless dogma? A
      matched case-control study.
AB  - On the basis of the growing evidence from randomized trials that routine
      prophylactic drainage is unnecessary in liver surgery or even harmful in chronic
      liver disease, we challenged the concept of prophylactic drainage in orthotopic
      liver transplantation (OLT). Since September 2006, we omitted drains in every
      patient who underwent OLT, regardless of the procedure. Thirty-five cadaveric
      OLTs were performed during a 12-month period. These patients were matched 1:2
      with 70 patients who had prophylactic drainage after OLT according to
      donor/recipient age, recipient gender, recipient body mass index, and Model for
      End-Stage Liver Disease (MELD) score. Endpoints were postoperative morbidity, in
      hospital mortality, intensive care unit (ICU), and hospital stay. Complications
      were graded according to a therapy-oriented classification (grades I-V). Both
      groups (no drainage, n = 35; drainage, n = 70) were comparable in terms of median
      donor age (47.5 versus 51.0 years), recipient age (50.6 versus 52.0 years), MELD
      score (18 versus 14), and body mass index (25.3 versus 26 kg/m(2)). Because of
      the increasing shortage of organs, more marginal grafts were used in the recent
      period (ie, no-drainage group): 49% (17/35) versus 27% (19/70; P = 0.04). Major
      complications were not different between groups: grade 3a
      (endoscopic/radiological intervention) in 20% (7/35) versus 16% (11/70; not
      significant), grade 3b (surgical intervention) in 23% (8/35) versus 17% (12/70;
      not significant), grade 4a (ICU therapy, intermittent hemodialysis) in 34%
      (12/35) versus 21% (15/70; not significant), grade 4b (multiorgan failure) in 14%
      (5/35) versus 10% (7/70; not significant), and grade 5 (death) in 6% (2/35)
      versus 7% (5/70; not significant). This matched case study challenges the dogma
      of prophylactic drainage after OLT. A no-drain strategy provided no disadvantages
      despite increased use of extended criteria donors in the no-drainage group.
      Prophylactic drainage appears unnecessary on a routine basis.

PMID- 19109840
TI  - Balloon dilation only versus balloon dilation plus stenting for
      posttransplantation biliary strictures.
AB  - BACKGROUND AND STUDY AIMS: Biliary strictures are a major cause of morbidity
      following liver transplantation. In the present prospective comparative trial, we
      evaluated balloon dilation vs. balloon dilation plus stenting with regard to
      technical and clinical efficacy as well as complications. PATIENTS AND METHODS: A
      total of 32 patients with symptomatic biliary strictures after liver
      transplantation were assigned to balloon dilation (n = 17) or balloon dilation
      plus plastic stent placement (n = 15). The main outcome parameter was sustained
      clinical success defined as an interval of at least 3 months without further
      endoscopic intervention. Additional outcome parameters were assisted clinical
      success and treatment failure, as well as procedure-related complications.
      RESULTS: The initial technical success and primary clinical success rates in the
      dilation group were both 100 %; in the stent group, the corresponding rates were
      100 % and 93 % (n.s.). The sustained clinical success was 71 % vs. 73 %,
      respectively (n. s.). The time interval to reach sustained clinical success was
      6.1 and 5.1 months, respectively (n. s.). No significant differences were found
      in assisted clinical success or in treatment failure. Complications were observed
      in 4.3 % in the dilation group and 13.6 % in the stent group (P < 0.05).
      Independent of the treatment group, a sustained clinical success in anastomotic
      strictures was achieved in 100 %, whereas the success rate of strictures of the
      donor hepatic duct was 50 % and of strictures involving the hilum, only 14 % (P <
      0.05). CONCLUSIONS: In patients with biliary strictures after liver
      transplantation, endoscopic balloon dilation alone was as effective as dilation
      plus stent placement. Stent placement was associated with a significantly higher
      complication rate. Endoscopic treatment of strictures of the biliary anastomosis
      is highly effective, whereas attempts to treat more complex strictures are less
      promising.

PMID- 19109841
TI  - Feasibility of adult-to-adult living donor liver transplantation for acute liver
      failure.

PMID- 19109844
TI  - Sildenafil therapy is associated with improved hemodynamics in liver
      transplantation candidates with pulmonary arterial hypertension.
AB  - Pulmonary arterial hypertension associated with portal hypertension occurs in
      about 5% of patients being evaluated for liver transplantation. Treatment is
      required to facilitate safe transplantation, and oral pulmonary vasodilators have
      yet to be prospectively evaluated for this disease. The objective of this study
      was to determine the hemodynamic outcome in a consecutive cohort of patients
      offered sildenafil as first-line treatment for portopulmonary hypertension. We
      identified consecutive patients at the University of Rochester referred by the
      liver transplant team. All had catheter-confirmed disease and were treated with
      sildenafil. Patients were excluded from analysis if they did not have follow-up
      catheterizations. The change in pulmonary vascular resistance at the time of
      first follow-up was the primary outcome. Eleven patients began sildenafil, and 9
      had follow-up right heart catheterizations during a 3-year period. Pulmonary
      vascular resistance dropped in each patient; as a group, the mean dropped from
      575 to 375 dynes/second/cm(5). Four of 9 patients achieved a mean pulmonary
      artery pressure </= 35 mm Hg at the time of first recatheterization, and 1
      patient received a successful cadaveric transplant. Four of 6 patients with more
      than 1 follow-up catheterization had sustained hemodynamic benefit. One patient
      initially responded to therapy with favorable hemodynamics but was found in the
      operating room to have recrudescent disease (on therapy) that precluded safe
      transplantation. In conclusion, sildenafil was associated with improved
      hemodynamics in this small, uncontrolled cohort. A multicenter, prospective
      evaluation is warranted in this group uniformly excluded from phase III clinical
      trials.

PMID- 19109843
TI  - Sildenafil monotherapy in portopulmonary hypertension can facilitate liver
      transplantation.
AB  - Portopulmonary hypertension (POPH), or pulmonary arterial hypertension associated
      with cirrhosis, carries a high mortality and often precludes liver
      transplantation. Many POPH patients have preserved or increased cardiac output;
      therefore, decreasing pulmonary artery pressure rather than improving cardiac
      output is more important in reducing liver transplant risk, and this makes
      sildenafil an attractive therapeutic option. We assessed the clinical response of
      patients with POPH treated with sildenafil monotherapy. We retrospectively
      reviewed the charts of 10 patients with POPH and sildenafil monotherapy. Eight of
      10 patients had hepatitis C virus infection. Patients took 31 +/- 14 mg (mean +/-
      standard deviation) thrice daily and were followed for 21 +/- 16 months. The
      World Health Organization functional class improved from 3.0 +/- 0.0 to 2.3 +/-
      0.5 at 1 year (P < 0.05). Four of 8 patients increased the 6-minute walk distance
      at 1 year by 30 m or more. Three patients became transplant-eligible, 1 of whom
      underwent successful transplantation, and 3 patients have been stable without
      progression of liver disease or POPH. The remainder were not transplant
      candidates because of refractory POPH (n = 2) or other comorbidities (n = 2). We
      conclude that sildenafil may be an effective therapy for POPH that can stabilize
      or improve hemodynamics in patients with POPH and thereby facilitate liver
      transplantation.

PMID- 19109845
TI  - Hepatic encephalopathy after liver transplantation in a patient with a normally
      functioning graft: Treatment with embolization of portosystemic collaterals.

PMID- 19109846
TI  - Impact of donor graft steatosis on overall outcome and viral recurrence after
      liver transplantation for hepatitis C virus cirrhosis.
AB  - The aim of this study was to determine the influence of donor graft steatosis on
      overall outcome, viral recurrence, and fibrosis progression in orthotopic liver
      transplantation (OLT) for hepatitis C virus (HCV) cirrhosis. One hundred twenty
      patients who underwent OLT for HCV cirrhosis between 1995 and 2005 were included
      in the study. Donor steatosis was categorized as absent (0%-10%; n = 40), mild
      (10%-30%; n = 32), moderate (30%-60%; n = 29), or severe (>60%; n = 19). A Cox
      multivariate analysis for marginal donor variables and a Model for End-Stage
      Liver Disease index were performed. Fibrosis evolution was analyzed in liver
      biopsies (fibrosis < 2 or > or =2) 3, 6, and 12 months post-OLT and in the late
      post-OLT period. Fifty-six grafts were lost (46%). The survival of the grafts was
      inversely proportional to donor liver steatosis: 82%, 72%, and 72% at 1, 2, and 3
      years post-OLT in the absence of steatosis; 73%, 63%, and 58% with mild
      steatosis; 74%, 62%, and 43% with moderate steatosis; and 62%, 49%, and 42% with
      severe steatosis (P = 0.012). HCV recurrence was earlier and more frequent in
      recipients with steatosis > 30% (46% versus 32% at 3 months, P = 0.017; 58%
      versus 43% at 6 months, P = 0.020; 70% versus 56% at 12 months, P = 0.058; and
      95% versus 69% at 3 years post-OLT, P = 0.0001). Graft survival was lower in
      alcoholic liver disease recipients versus HCV recipients when steatosis was >30%
      at 3, 6, and 12 months post-OLT (P = 0.042) but not when steatosis was <30% (P =
      0.53). A higher fibrosis score was obtained 3 months post-OLT (P = 0.033), 6
      months post-OLT (P = 0.306), 12 months post-OLT (P = 0.035), and in the late post
      OLT period (P = 0.009). In conclusion, donor graft steatosis influences the
      outcome of OLT for HCV cirrhosis. HCV recurrence is more frequent and earlier in
      recipients of moderately and severely steatotic livers. Fibrosis evolution is
      higher when graft steatosis is >30%. OLT with >30% steatotic donor livers should
      be precluded in HCV recipients.

PMID- 19109847
TI  - Simplified technique for one-orifice vein reconstruction in left-lobe liver
      transplantation.

PMID- 19109848
TI  - Subnormothermic machine perfusion protects steatotic livers against preservation
      injury: a potential for donor pool increase?
AB  - We tested whether rat liver preservation performed by machine perfusion (MP) at
      20 degrees C can enhance the functional integrity of steatotic livers versus
      simple cold storage. We also compared MP at 20 degrees C with hypothermic MP at 8
      degrees C, and 4 degrees C. Obese and lean male Zucker rats were used as liver
      donors. MP was performed for 6 hours with a glucose and N-acetylcysteine
      supplemented Krebs-Henseleit solution. Both MP and cold storage preserved livers
      were reperfused with Krebs-Henseleit solution (2 hours at 37 degrees C). MP at 4
      degrees C and 8 degrees C reduced the fatty liver necrosis compared with cold
      storage but we further protected the organs using MP at 20 degrees C. Necrosis
      did not differ in livers from lean animals submitted to the different procedures;
      the enzymes released in steatotic livers preserved by MP at 20 degrees C were
      similar to those showed in nonsteatotic organs. The adenosine
      triphosphate/adenosine diphosphate ratio and bile production were higher and the
      oxidative stress and biliary enzymes were lower in steatotic livers preserved by
      MP at 20 degrees C as compared with cold storage. In livers from lean rats, the
      adenosine triphosphate/adenosine diphosphate ratio appears better conserved by MP
      at 20 degrees C as compared with cold storage. In steatotic livers preserved by
      cold storage, a 2-fold increase in tumor necrosis factor-alpha levels and caspase
      3 activity was observed as compared with organs preserved by MP at 20 degrees C.
      These data are substantiated by better morphology, higher glycogen content, and
      lower reactive oxygen species production by sinusoidal cells in steatotic liver
      submitted to MP at 20 degrees C versus cold storage. MP at 20 degrees C improves
      cell survival and leads to a marked improvement in hepatic preservation of
      steatotic livers as compared with cold storage.

PMID- 19109849
TI  - Cirrhosis of mixed etiology (hepatitis C virus and alcohol): Posttransplantation
      outcome-Comparison with hepatitis C virus-related cirrhosis and alcoholic-related
      cirrhosis.
AB  - Hepatitis C virus (HCV)-related liver disease is enhanced by alcohol consumption.
      Of HCV-related liver transplantation (LT) recipients, 25% have a history of
      alcohol intake. The purpose of this research was to determine whether LT outcome
      differs between patients with cirrhosis of mixed etiology compared to HCV or
      alcohol alone. Of 494 LT (1997-2001), recipient/donor features, post-LT
      histological, metabolic complications [hypertension, diabetes-diabetes mellitus
      (DM)], and de novo tumors were compared in 3 groups [HCV-related cirrhosis = 170
      (HCV group), alcohol-related cirrhosis (alcohol group) = 107, and cirrhosis of
      mixed etiology (mixed group) = 60]. Protocol biopsies were done in HCV patients.
      Severe recurrent HCV disease was defined as: 1-year fibrosis >1, cholestatic
      hepatitis, recurrent cirrhosis, or HCV-related liver retransplantation (reLT)
      within 5 years. Patients in the mixed group were younger (mean age: HCV group =
      59 years; mixed group = 49 years; alcohol group = 53 years; P < 0.05) and mainly
      men (% men: HCV group = 51%; mixed group = 97%; alcohol group = 87%).
      Hepatocellular carcinoma (HCC) was more frequent in HCV patients (HCV group =
      44%; mixed group = 35%; alcohol group = 18%; P = 0.05). Five-year survival was
      lowest in the HCV group (HCV group = 49% versus mixed group = 73% versus alcohol
      group = 76%; and P < 0.01 for the HCV group versus the alcohol group or the HCV
      group versus the mixed group; P = 0.74 for the alcohol group versus the mixed
      group). Metabolic complications and de novo tumors were more frequent in the
      alcohol groups. Severe HCV disease was similar in the HCV+ groups (HCV group =
      45%; mixed group = 45%; P = 0.66). Patients with in the mixed group were more
      frequently treated with antivirals (32% versus HCV group = 18%; P = 0.03). In HCV
      patients, factors independently associated with lower survival were older donor
      age, LT indication (HCV alone), and increased body mass index (BMI). Antiviral
      therapy was a protective factor. Post-LT survival was lower in the isolated HCV
      group compared to the alcohol or mixed groups despite a similar recurrence of HCV
      disease. A greater use of antiviral therapy in the mixed group may explain these
      differences. The incidence of metabolic complications and de novo tumors was
      greater in the alcohol groups.

PMID- 19109850
TI  - New concepts in liver preservation: how the pendulum sways back.

PMID- 19109851
TI  - Diffusion of innovations: smartphones and wireless anatomy learning resources.
AB  - The author has previously reported on principles of diffusion of innovations, the
      processes by which new technologies become popularly adopted, specifically in
      relation to anatomy and education. In presentations on adopting handheld
      computers [personal digital assistants (PDAs)] and personal media players for
      health sciences education, particular attention has been directed to the
      anticipated integration of PDA functions into popular cellular telephones.
      However, limited distribution of early "smartphones" (e.g., Palm Treo and
      Blackberry) has provided few potential users for anatomical learning resources.
      In contrast, iPod media players have been self-adopted by millions of students,
      and "podcasting" has become a popular medium for distributing educational media
      content. The recently introduced Apple iPhone has combined smartphone and higher
      resolution media player capabilities. The author successfully tested the iPhone
      and the "work alike" iPod touch wireless media player with text-based "flashcard"
      resources, existing PDF educational documents, 3D clinical imaging data, lecture
      "podcasts," and clinical procedure video. These touch-interfaced, mobile
      computing devices represent just the first of a new generation providing
      practical, scalable wireless Web access with enhanced multimedia capabilities.
      With widespread student self-adoption of such new personal technology, educators
      can look forward to increasing portability of well-designed, multiplatform "learn
      anywhere" resources.

PMID- 19109852
TI  - Improved learning efficiency and increased student collaboration through use of
      virtual microscopy in the teaching of human pathology.
AB  - The implementation of virtual microscopy in the teaching of pathology at the
      Bloomington, Indiana extension of the Indiana University School of Medicine
      permitted the assessment of student attitudes, use and academic performance with
      respect to this new technology. A gradual and integrated approach allowed the
      parallel assessment with respect to both the virtual and optical microscopes.
      Student survey data indicated that the virtual imaging technology was
      enthusiastically received, and aggregate grade comparisons with the previous
      classes showed no decrease in content mastery. Survey questions assessing a
      variety of parameters reveal improved time and resource utilization, as well as
      increased student collaboration. Even so, 50% of the respondents indicated having
      both optical and virtual microscopes available was preferable.

PMID- 19109853
TI  - The impact of interactive, computerized educational modules on preclinical
      medical education.
AB  - Interactive computerized modules have been linked to improved retention of
      material in clinical medicine. This study examined the effects of a new series of
      interactive learning modules for preclinical medical education, specifically in
      the areas of quiz performance, perceived difficulty of concepts, study time, and
      perceived stress level. We randomly allocated 102 medical student volunteers into
      control and experimental groups. All participants studied selected anatomical and
      physiologic concepts using existing material (lecture notes, textbooks, etc.),
      while those in the experimental groups used the new interactive modules as well.
      All participants completed a quiz to test their knowledge of the assigned
      concepts and a survey to assess their subjective experiences in studying with the
      modules. We found a trend toward higher quiz scores in the experimental group
      relative to the control group, though it did not reach statistical significance
      (P = 0.31). Perceived concept difficulty was significantly reduced among those
      who studied with the modules (P < 0.001), and the number of hours spent studying
      the concepts was significantly increased (P = 0.028). Of those who used the
      modules, 83% rated them as "very helpful" or "extremely helpful." No significant
      differences existed between participants' reported stress levels during the
      course of the study (P = 0.44). Our data suggest that medical students may learn
      more effectively and feel less intimidated by difficult concepts when interactive
      modules supplement traditional instruction.

PMID- 19109854
TI  - Medical student retention of embryonic development: impact of the dimensions
      added by multimedia tutorials.
AB  - The purpose of this project was to develop Web-based learning modules that
      combine (1) animated 3D graphics; (2) 3D models that a student can manipulate
      independently; (3) passage of time in embryonic development; and (4) animated 2D
      graphics, including 2D cross-sections that represent different "slices" of the
      embryo, and animate in parallel. These elements were presented in two tutorials,
      one depicting embryonic folding and the other showing development of the nervous
      system after neural tube formation. The goal was to enhance the traditional
      teaching format-lecture combined with printed diagrams, text, and existing
      computer animations-with customized, guided, Web-based learning modules that
      surpassed existing resources. To assess module effectiveness, we compared quiz
      performance of control groups who attended lecture and did not use a supporting
      module, with study groups who used a module in addition to attending lecture. We
      also assessed our students' long-term retention of the material, comparing
      classes who had used the module with students from a previous year that had not
      seen the module. Our data analysis suggests that students who used a module
      performed better than those given only traditional resources if they used the
      module after they were already somewhat familiar with the material. The findings
      suggest that our modules-and possibly computer-assisted-instruction modules in
      general-are more useful if used toward the later stages of learning, rather than
      as an initial resource. Furthermore, our data suggest that the animation aids in
      long-term retention. Both medical students at the University of Cincinnati and
      medical faculty from across the country commented favorably on their experiences
      with the embryonic development modules.

PMID- 19109855
TI  - Interprofessional education in gross anatomy: experience with first-year medical
      and physical therapy students at Mayo Clinic.
AB  - Interprofessional education (IPE) in clinical practice is believed to improve
      outcomes in health care delivery. Integrating teaching and learning objectives
      through cross discipline student interaction in basic sciences has the potential
      to initiate interprofessional collaboration at the early stages of health care
      education. Student attitudes and effectiveness of IPE in the context of a
      combined gross anatomy course for first-year students in Doctor of Physical
      Therapy (DPT) and Doctor of Medicine (MD) degrees curricula were evaluated.
      Integrated teams of MD and DPT students participated in part of the gross anatomy
      dissection course at Mayo Medical School. A survey was administered to 42 MD and
      28 DPT students that assessed their attitudes toward IPE and cooperation among
      health care professionals. Pre- and post-experience surveys were evaluated.
      Positive comments were related to opportunities for developing a better
      understanding of the nature and scope of each other's programs, encouraging
      teamwork and communication, mutual respect, and reducing the perceptual divide
      between disciplines. Ninety-two percent of the students agreed that
      interprofessional learning would help them in becoming a more effective member of
      the health care team. This initial experience with IPE in gross anatomy provides
      a basis for continued development of interdisciplinary educational strategies.

PMID- 19109856
TI  - The importance of exposure to human material in anatomical education: a
      philosophical perspective.
AB  - Despite reductions in the importance, time committed to, and status of anatomical
      education in modern medical curricula, anatomical knowledge remains a cornerstone
      of medicine and related professions. Anatomists are therefore presented with the
      challenge of delivering required levels of core anatomical knowledge in a reduced
      time-frame and with fewer resources. One common response to this problem is to
      reduce the time available for students to interact with human specimens (either
      via dissection or handling of prosected material). In some curricula, these
      sessions are replaced with didactic or problem-based approaches focussed on
      transmitting core anatomical concepts. Here, I propose that the adoption of
      philosophical principles concerning the relationship and differences between
      "direct experience" and "concept" provides a strong case in support of requiring
      students to gain significant exposure to human material. These insights support
      the hypothesis that direct experience of human material is required for "deep,"
      rather than "superficial," understanding of anatomy.

PMID- 19109857
TI  - The development of clinical reasoning skills: a major objective of the anatomy
      course.
AB  - Traditional medical school curricula have made a clear demarcation between the
      basic biomedical sciences and the clinical years. It is our view that a
      comprehensive medical education necessarily involves an increased correlation
      between basic science knowledge and its clinical applications. A basic anatomy
      course should have two main objectives: for the student to successfully gain a
      solid knowledge base of human anatomy and to develop and hone clinical reasoning
      skills. In a basic anatomy course, clinical case discussions based on underlying
      anatomic anomalies or abnormalities are the major means to teach students
      clinical reasoning skills. By identifying, classifying, and analyzing the
      clinical data given, a student learns to methodically approach a clinical case
      and formulate plausible diagnoses. Practicing and perfecting clinical problem
      solving skills should be a major objective of the anatomy curriculum. Such
      clinical reasoning skills are indeed crucial for the successful and expert
      practice of medicine.

PMID- 19109858
TI  - Impact of cadaver dissection: working toward solutions.

PMID- 19109860
TI  - Spectrum of non-inflammatory bowel disease and non-infectious colitis.
AB  - A variety of inflammatory diseases of the colon, which can be differentiated from
      inflammatory bowel disease (IBD) and infectious colitis by their clinical,
      endoscopic and histological characteristics, are reported as non-IBD and non
      infectious colitis. These diseases include microscopic colitis, ischemic colitis,
      segmental colitis associated with diverticula, radiation colitis, diversion
      colitis, eosinophilic colitis and Behcet's colitis. The etiopathogenesis of most
      of these diseases remains obscure and the epidemiological data are rather
      limited. These conditions are often troublesome for the patient and are
      associated with diagnostic difficulties for the physician. In many cases the
      treatment is empirical and there is a need for future research using randomized
      controlled trials.

PMID- 19109861
TI  - Diagnosis and management of microscopic colitis.
AB  - Microscopic colitis, comprising collagenous and lymphocytic colitis, is
      characterized clinically by chronic watery diarrhea, and a macroscopically normal
      colonic mucosa where diagnostic histopathological features are seen on
      microscopic examination. The annual incidence of each disorder is 4-6/100,000
      inhabitants, with a peak incidence in 60-70-year-old individuals and a noticeable
      female predominance for collagenous colitis. The etiology is unknown. Chronic
      diarrhea, abdominal pain, weight loss, fatigue and fecal incontinence are common
      symptoms, which impair the health-related quality of life of the patient. There
      is an association with other autoimmune disorders such as celiac disease,
      diabetes mellitus, thyroid disorders and arthritis. Budesonide is the best
      documented short-term treatment, but the optimal long-term strategy needs further
      study. The long-term prognosis is good and the risk of complications including
      colonic cancer is low.

PMID- 19109862
TI  - Recent advances in the management of radiation colitis.
AB  - Radiation colitis, an insidious, progressive disease of increasing frequency,
      develops 6 mo to 5 years after regional radiotherapy for malignancy, owing to the
      deleterious effects of the latter on the colon and the small intestine. When
      dealing with radiation colitis and its complications, the most conservative
      modality should be employed because the areas of intestinal injury do not tend to
      heal. Acute radiation colitis is mostly self-limited, and usually, only
      supportive management is required. Chronic radiation colitis, a poorly
      predictable progressive disease, is considered as a precancerous lesion;
      radiation-associated malignancy has a tendency to be diagnosed at an advanced
      stage and to bear a dismal prognosis. Therefore, management of chronic radiation
      colitis remains a major challenge owing to the progressive evolution of the
      disease, including development of fibrosis, endarteritis, edema, fragility,
      perforation, partial obstruction, and cancer. Patients are commonly managed
      conservatively. Surgical intervention is difficult to perform because of the
      extension of fibrosis and alterations in the gut and mesentery, and should be
      reserved for intestinal obstruction, perforation, fistulas, and severe bleeding.
      Owing to the difficulty in managing the complications of acute and chronic
      radiation colitis, particular attention should be focused onto the prevention
      strategies. Uncovering the fibrosis mechanisms and the molecular events
      underlying radiation bowel disease could lead to the introduction of new
      therapeutic and/or preventive approaches. A variety of novel, mostly
      experimental, agents have been used mainly as a prophylaxis, and improvements
      have been made in radiotherapy delivery, including techniques to reduce the
      amount of exposed intestine in the radiation field, as a critical strategy for
      prevention.

PMID- 19109863
TI  - Ischemic colitis: clinical practice in diagnosis and treatment.
AB  - Ischemic colitis is the most common form of ischemic injury of the
      gastrointestinal tract and can present either as an occlusive or a non-occlusive
      form. It accounts for 1 in 1000 hospitalizations but its incidence is
      underestimated because it often has a mild and transient nature. The etiology of
      ischemic colitis is multifactorial and the clinical presentation variable. The
      diagnosis is based on a combination of clinical suspicion, radiographic,
      endoscopic and histological findings. Therapy and outcome depends on the severity
      of the disease. Most cases of the non-gangrenous form are transient and resolve
      spontaneously without complications. On the other hand, high morbidity and
      mortality and urgent operative intervention are the hallmarks of gangrenous
      ischemic colitis.

PMID- 19109864
TI  - Diagnosis and management of splanchnic ischemia.
AB  - Splanchnic or gastrointestinal ischemia is rare and randomized studies are
      absent. This review focuses on new developments in clinical presentation,
      diagnostic approaches, and treatments. Splanchnic ischemia can be caused by
      occlusions of arteries or veins and by physiological vasoconstriction during low
      flow states. The prevalence of significant splanchnic arterial stenoses is high,
      but it remains mostly asymptomatic due to abundant collateral circulation. This
      is known as chronic splanchnic disease (CSD). Chronic splanchnic syndrome (CSS)
      occurs when ischemic symptoms develop. Ischemic symptoms are characterized by
      postprandial pain, fear of eating and weight loss. CSS is diagnosed by a test for
      actual ischemia. Recently, gastro-intestinal tonometry has been validated as a
      diagnostic test to detect splanchnic ischemia and to guide treatment. In single
      vessel CSD, the complication rate is very low, but some patients have ischemic
      complaints, and can be treated successfully. In multi-vessel stenoses, the
      complication rate is considerable, while most have CSS and treatment should be
      strongly considered. CT and MR-based angiographic reconstruction techniques have
      emerged as alternatives for digital subtraction angiography for imaging of
      splanchnic vessels. Duplex ultrasound is still the first choice for screening
      purposes. The strengths and weaknesses of each modality will be discussed. CSS
      may be treated by minimally invasive endoscopic treatment of the celiac axis
      compression syndrome, endovascular antegrade stenting, or laparotomy-assisted
      retrograde endovascular recanalization and stenting. The treatment plan is highly
      individualized and is mainly based on precise vessel anatomy, body weight, co
      morbidity and severity of ischemia.

PMID- 19109865
TI  - Scutellaria barbate extract induces apoptosis of hepatoma H22 cells via the
      mitochondrial pathway involving caspase-3.
AB  - AIM: To study the growth inhibitory and apoptotic effects of Scutellaria barbata
      D.Don (S. barbata) and to determine the underlying mechanism of its antitumor
      activity in mouse liver cancer cell line H22. METHODS: Proliferation of H22 cells
      was examined by MTT assay. Cellular morphology of PC-2 cells was observed under
      fluorescence microscope and transmission electron microscope (EM). Mitochondrial
      transmembrane potential was determined under laser scanning confocal microscope
      (LSCM) with rhodamine 123 staining. Flow cytometry was performed to analyze the
      cell cycle of H22 cells with propidium iodide staining. Protein level of
      cytochrome C and caspase-3 was measured by semi-quantitive RT-PCR and Western
      blot analysis. Activity of caspase-3 enzyme was measured by spectrofluorometry.
      RESULTS: MTT assay showed that extracts from S. barbata (ESB) could inhibit the
      proliferation of H22 cells in a time-dependent manner. Among the various phases
      of cell cycle, the percentage of cells in S phase was significantly decreased,
      while the percentage of cells in G(1) phase was increased. Flow cytometry assay
      also showed that ESB had a positive effect on apoptosis. Typical apoptotic
      morphologies such as condensation and fragmentation of nuclei and blebbing
      membrane of apoptotic cells could be observed under transmission electron
      microscope and fluorescence microscope. To further investige the molecular
      mechanism behind ESB-induced apoptosis, ESB-treated cells rapidly lost their
      mitochondrial transmembrane potential, released mitochondrial cytochrome C into
      cytosol, and induced caspase-3 activity in a dose-dependent manner. CONCLUSION:
      ESB can effectively inhibit the proliferation and induce apoptosis of H22 cells
      involving loss of mitochondrial transmembrane potential, release of cytochrome C,
      and activation of caspase-3.

PMID- 19109866
TI  - MLH1 promoter germline-methylation in selected probands of Chinese hereditary non
      polyposis colorectal cancer families.
AB  - AIM: To detect the MLH1 gene promoter germline-methylation in probands of Chinese
      hereditary nonpolyposis colorectal cancer (HNPCC), and to evaluate the role of
      methylation in MLH1 gene promoter and molecular genetics in screening for HNPCC.
      METHODS: The promoter germline methylation of MLH1 gene was detected by
      methylation-specific PCR (MSP) in 18 probands from unrelated HNPCC families with
      high microsatellite-instability (MSI-H) phenotype but without germline mutations
      in MSH2, MLH1 and MSH6 genes. At the same time, 6 kindreds were collected with
      microsatellite-stability (MSS) phenotype but without germline mutations in MSH2,
      MLH1 and MSH6 genes as controls. The results of MSP were confirmed by clone
      sequencing. To ensure the reliability of the results, family H65 with nonsense
      germline mutation at c.2228C > A in MSH2 gene was used as the negative control
      and the cell line sw48 was used as the known positive control along with water as
      the blank control. Immunochemical staining of MLH1 protein was performed with
      Envision two-step method in those patients with aberrant methylation to judge
      whether the status of MLH1 gene methylation affects the expression of MLH1
      protein. RESULTS: Five probands with MLH1 gene promoter methylation were detected
      in 18 Chinese HNPCC families with MSI-H phenotype but without germline mutations
      in MSH2, MLH1 and MSH6 genes. Two of the five probands from families H10 and H29
      displayed exhaustive-methylation, fulfilling the Japanese criteria (JC) and the
      Amsterdam criteria (AC), respectively. The other 3 probands presented part
      methylation fulfilling the AC. Of the 13 probands with unmethylation phenotype, 8
      fulfilled the JC and the Bethesda guidelines (BG), 5 fulfilled the AC. The rate
      of aberrant methylation in MLH1 gene in the AC group (22.2%, 4/18) was higher
      than that in the JC/BG groups (5.6%, 1/18) in all HNPCC families with MSI-H
      phenotype but without germline mutations in MSH2, MLH1 and MSH6 genes. However,
      no proband with methylation in MLH1 gene was found in the families with MSS
      phenotype and without germline mutations in MSH2, MLH1 and MSH6 genes. No
      expression of MLH1 protein was found in tumor tissues from two patients with
      exhaustive-methylation phenotype, whereas positive expression of MLH1 protein was
      observed in tumor tissues from patients with partial methylation phenotype
      (excluding family H42 without tumor tissue), indicating that exhaustive
      methylation of MLH1 gene can cause defective expression of MLH1 protein.
      CONCLUSION: Methylation phenotype of MLH1 gene is correlated with microsatellite
      phenotype of MMR genes, especially with MSI-H. Exhaustive-methylation of MLH1
      gene can silence the expression of MLH1 protein. MLH1 promoter methylation
      analysis is a promising tool for molecular genetics screening for HNPCC.

PMID- 19109867
TI  - Metrically measuring liver biopsy: a chronic hepatitis B and C computer-aided
      morphologic description.
AB  - AIM: To describe a quantitative analysis method for liver biopsy sections with a
      machine that we have named "Dioguardi Histological Metriser" which automatically
      measures the residual hepatocyte mass (including hepatocytes vacuolization),
      inflammation, fibrosis and the loss of liver tissue tectonics. METHODS: We
      analysed digitised images of liver biopsy sections taken from 398 patients. The
      analysis with Dioguardi Histological Metriser was validated by comparison with
      semi-quantitative scoring system. RESULTS: The method provides: (1) the metrical
      extension in two-dimensions (the plane) of the residual hepatocellular set,
      including the area of vacuoles pertinent to abnormal lipid accumulation; (2) the
      geometric measure of the inflammation basin, which distinguishes intra-basin
      space and extra-basin dispersed parenchymal leukocytes; (3) the magnitude of
      collagen islets, (which were considered truncated fractals and classified into
      three degrees of magnitude); and (4) the tectonic index that quantifies
      alterations (disorders) in the organization of liver tissue. Dioguardi
      Histological Metriser machine allows to work at a speed of 0.1 mm(2)/s, scanning
      a whole section in 6-8 min. CONCLUSION: The results are the first standardized
      metrical evaluation of the geometric properties of the parenchyma, inflammation,
      fibrosis, and alterations in liver tissue tectonics of the biopsy sections. The
      present study confirms that biopsies are still valuable, not only for diagnosing
      chronic hepatitis, but also for quantifying changes in the organization and order
      of liver tissue structure.

PMID- 19109868
TI  - Disruption of colonic barrier function and induction of mediator release by
      strains of Campylobacter jejuni that invade epithelial cells.
AB  - AIM: To study the mechanisms by which Campylobacter jejuni (C. jejuni) causes
      inflammation and diarrhea. In particular, direct interactions with intestinal
      epithelial cells and effects on barrier function are poorly under-stood. METHODS:
      To model the initial pathogenic effects of C. jejuni on intestinal epithelium,
      polarized human colonic HCA-7 monolayers were grown on permeabilized filters and
      infected apically with clinical isolates of C. jejuni. Integrity of the monolayer
      was monitored by changes in monolayer resistance, release of lactate
      dehydrogenase, mannitol fluxes and electron microscopy. Invasion of HCA-7 cells
      was assessed by a modified gentamicin protection assay, translocation by counting
      colony forming units in the basal chamber, stimulation of mediator release by
      immunoassays and secretory responses in monolayers stimulated by bradykinin in an
      Ussing chamber. RESULTS: All strains translocated across monolayers but only a
      minority invaded HCA-7 cells. Strains that invaded HCA-7 cells destroyed
      monolayer resistance over 6 h, accompanied by increased release of lactate
      dehydrogenase, a four-fold increase in permeability to [(3)H] mannitol, and
      ultrastructural disruption of tight junctions, with rounding and lifting of cells
      off the filter membrane. Synthesis of interleukin (IL)-8 and prostaglandin E(2)
      was increased with strains that invaded the monolayer but not with those that did
      not. CONCLUSION: These data demonstrate two distinct effects of C. jejuni on
      colonic epithelial cells and provide an informative model for further
      investigation of initial host cell responses to C. jejuni.

PMID- 19109870
TI  - Adverse events with bismuth salts for Helicobacter pylori eradication: systematic
      review and meta-analysis.
AB  - AIM: To assess the safety of bismuth used in Helicobacter pylori (H pylori)
      eradication therapy regimens. METHODS: We conducted a systematic review and meta
      analysis. MEDLINE and EMBASE were searched (up to October 2007) to identify
      randomised controlled trials comparing bismuth with placebo or no treatment, or
      bismuth salts in combination with antibiotics as part of eradication therapy with
      the same dose and duration of antibiotics alone or, in combination, with acid
      suppression. Total numbers of adverse events were recorded. Data were pooled and
      expressed as relative risks with 95% confidence intervals (CI). RESULTS: We
      identified 35 randomised controlled trials containing 4763 patients. There were
      no serious adverse events occurring with bismuth therapy. There was no
      statistically significant difference detected in total adverse events with
      bismuth [relative risk (RR) = 1.01; 95% CI: 0.87-1.16], specific individual
      adverse events, with the exception of dark stools (RR = 5.06; 95% CI: 1.59
      16.12), or adverse events leading to withdrawal of therapy (RR = 0.86; 95% CI:
      0.54-1.37). CONCLUSION: Bismuth for the treatment of H pylori is safe and well
      tolerated. The only adverse event occurring significantly more commonly was dark
      stools.

PMID- 19109869
TI  - Magnolol attenuates sepsis-induced gastrointestinal dysmotility in rats by
      modulating inflammatory mediators.
AB  - AIM: To investigate the protective effects of magnolol on sepsis-induced
      inflammation and intestinal dysmotility. METHODS: Sepsis was induced by a single
      intraperitoneal injection of lipopolysaccharide (LPS). Male Wistar rats were
      randomly assigned to one of three treatment groups: magnolol prior to LPS
      injection (LPS/Mag group); vehicle prior to LPS injection (LPS/Veh group);
      vehicle prior to injection of saline (Control/Veh). Intestinal transit and
      circular muscle mechanical activity were assessed 12 h after LPS injection. Tumor
      necrosis factor-alpha (TNF-alpha), interleukin-10 (IL-10), monocyte
      chemoattractant protein-1 (MCP-1) and inducible nitric oxide synthase (iNOS) mRNA
      in rat ileum were studied by RT-PCR 2 h after LPS injection. Nuclear factor
      kappaB (NF-kappaB) activity in the intestine was also investigated at this time
      using electrophoretic mobility shift assay. In addition, antioxidant activity was
      determined by measuring malondialdehyde (MDA) concentration and superoxide
      dismutase (SOD) activity in the intestine 2 h after LPS injection. RESULTS:
      Magnolol significantly increased intestinal transit and circular muscle
      mechanical activity in LPS-treated animals. TNF-alpha, MCP-1 and iNOS mRNA
      expression in the small intestine were significantly reduced after magnolol
      treatment in LPS-induced septic animals, compared with untreated septic animals.
      Additionally, magnolol significantly increased IL-10 mRNA expression in septic
      rat ileum. Magnolol also significantly suppressed NF-kappaB activity in septic
      rat intestine. In addition, magnolol significantly decreased MDA concentration
      and increased SOD activity in rat ileum. CONCLUSION: Magnolol prevents sepsis
      induced suppression of intestinal motility in rats. The potential mechanism of
      this benefit of magnolol appears to be modulation of self-amplified inflammatory
      events and block of oxidative stress in the intestine.

PMID- 19109871
TI  - Changing patterns of hepatitis A prevalence within the Saudi population over the
      last 18 years.
AB  - AIM: To determine the seroprevalence of Hepatitis A (HAV) amongst Saudi children
      and compare it with previously reported prevalence data from the same population.
      METHODS: A total of 1357 students were randomly selected between the ages of 16
      and 18 years (689 males and 668 females) from three different regions of Saudi
      Arabia (Madinah, Al-Qaseem, and Aseer) and tested for anti-HAV-IgG. RESULTS: The
      overall prevalence of anti-HAV-IgG among the study population was 18.6%. There
      was no difference between males and females but there was a significant
      difference in the seroprevalence (P = 0.0001) between the three different
      regions, with Madinah region showing the highest prevalence (27.4%). When
      classified according to socioeconomic status, lower class students had a
      prevalence of 36.6%, lower middle class 16.6%, upper middle class 9.6%, and upper
      class 5.9% (P = 0.0001). Comparing the current study results with those of
      previous studies in 1989 and 1997 involving the same population, there was a
      marked reduction in the overall prevalence of HAV from 52% in 1989, to 25% in
      1997, to 18.6% in 2008 (P < 0.0001). CONCLUSION: Over the last 18 years, there
      has been a marked decline in the prevalence of HAV in Saudi children and
      adolescents. The current low prevalence rates call for strict adherence to
      vaccination policies in high-risk patients and raises the question of a universal
      HAV vaccination program.

PMID- 19109872
TI  - Prevalence of celiac disease in Iranian children with idiopathic short stature.
AB  - AIM: To determine the prevalence of celiac disease (CD) in children with
      idiopathic short stature (ISS) and the diagnostic value of immunoglobulin (Ig) A
      G antigliadin antibodies (AGA) and transglutaminase (TTG) antibodies for CD.
      METHODS: A total of 104 children (49 male, 55 female) with ISS without a specific
      etiology were studied. Extensive endocrine investigations had shown no
      abnormalities in any subject. Anthropometric parameters and IgA AGA and IgA TTG
      antibodies were evaluated in this study group. These antibodies were measured by
      enzyme-linked immunosorbent assay. All patients were referred for an endoscopic
      intestinal biopsy. The biopsy samples were classified according to revised Marsh
      criteria (UEGW 2001). RESULTS: We detected positive IgA TTG antibodies in 36 and
      IgA AGA in 35 of these patients. Thirty one IgA TTG antibody positive and 28 IgA
      AGA positive subjects showed histological abnormalities compatible with celiac
      disease (33.6%). Sensitivity, specificity, positive predictive value (PPV) and
      negative predictive value for IgA AGA were found to be 80%, 88.4%, 77.8% and
      89.7%, respectively. Sensitivity, specificity and PPV for IgA TTG antibodies were
      88.6%, 94.2% and 88.6%, respectively. CONCLUSION: We conclude that the prevalence
      of celiac disease is high in patients with ISS and it is important to test all
      children with ISS for celiac disease by measuring serologic markers and
      performing an intestinal biopsy.

PMID- 19109873
TI  - Gluten sensitive enteropathy in patients with iron deficiency anemia of unknown
      origin.
AB  - AIM: To determine the prevalence of gluten sensitive enteropathy (GSE) in a large
      group of patients with iron deficiency anemia (IDA) of obscure origin. METHODS:
      In this cross-sectional study, patients with IDA of obscure origin were screened
      for GSE. Anti-endomysial antibody (EMA) and tissue transglutaminase antibody
      (tTG) levels were evaluated and duodenal biopsies were taken and scored according
      to the Marsh classification. The diagnosis of GSE was based on a positive
      serological test and abnormal duodenal histology. Gluten free diet (GFD) was
      advised for all the GSE patients. RESULTS: Of the 4120 IDA patients referred to
      our Hematology departments, 206 (95 male) patients were found to have IDA of
      obscure origin. Thirty out of 206 patients (14.6%) had GSE. The mean age of GSE
      patients was 34.6 +/- 17.03 (range 10-72 years). The female to male ratio was
      1.3:1. Sixteen patients had Marsh 3, 12 had Marsh 2, and 2 had Marsh 1 lesions.
      The severity of anemia was in parallel with the severity of duodenal lesions.
      Twenty-two GSE patients (73.3%) had no gastrointestinal symptoms. Fourteen GSE
      patients who adhered to GFD without receiving iron supplementation agreed to
      undergo follow up visits. After 6 mo of GFD, their mean hemoglobin levels (Hb)
      increased from 9.9 +/- 1.6 to 12.8 +/- 1.0 g/dL (P < 0.01). Interestingly, in 6
      out of 14 patients who had Marsh 1/2 lesions (e.g. no villous atrophy) on
      duodenal biopsy, mean Hb increased from 11.0 +/- 1.1 to 13.1 +/- 1.0 g/dL (P <
      0.01) while they did not receive any iron supplementation. CONCLUSION: There is a
      high prevalence (e.g. 14.6%) of GSE in patients with IDA of obscure origin.
      Gluten free diet can improve anemia in GSE patients who have mild duodenal
      lesions without villous atrophy.

PMID- 19109874
TI  - Inhibitory effect of modified citrus pectin on liver metastases in a mouse colon
      cancer model.
AB  - AIM: To discuss the expression of glactin-3 in liver metastasis of colon cancer
      and its inhibition by modified citrus pectin (MCP) in mice. METHODS: Seventy-five
      Balb/c mice were randomly divided into negative control group (n = 15), positive
      control group (n = 15), low MCP concentration group (n = 15), middle MCP
      concentration group (n = 15) and high MCP concentration group (n = 15). CT26
      colon cancer cells were injected into the subcapsule of mouse spleen in positive
      control group, low, middle and high MCP concentrations groups, except in negative
      control, to set up a colon cancer liver metastasis model. The concentration of
      MCP in drinking water was 0.0%, 0.0%, 1.0%, 2.5% and 5.0% (wt/vol), respectively.
      Liver metastasis of colon cancer was observed after 3 wk. Enzyme-linked
      immunosorbent assay (ELISA) was used to detect the concentration of galectin-3 in
      serum. Expression of galectin-3 in liver metastasis was detected by
      immunohistochemistry. RESULTS: Except for the negative group, the percentage of
      liver metastasis in the other 4 groups was 100%, 80%, 73.3% and 60%,
      respectively. The number of liver metastases in high MCP concentration group was
      significantly less than that in positive control group (P = 0.008). Except for
      the negative group, the median volume of implanted spleen tumor in the other 4
      groups was 1.51 cm(3), 0.93 cm(3), 0.77 cm(3) and 0.70 cm(3), respectively. The
      volume of implanted tumor in middle and high MCP concentration groups was
      significantly smaller than that in positive control group (P = 0.019; P = 0.003).
      The concentration of serum galectin-3 in positive control and MCP treatment
      groups was significantly higher than that in the negative control group. However,
      there was no significant difference between them. Except for the negative control
      group, the expression of galectin-3 in liver metastases of the other 4 groups
      showed no significant difference. CONCLUSION: Expression of galetin-3 increases
      significantly in liver metastasis of colon cancer, which can be effectively
      inhibited by MCP.

PMID- 19109875
TI  - Melatonin protects liver from intestine ischemia reperfusion injury in rats.
AB  - AIM: To investigate the protective effect of melatonin on liver after intestinal
      ischemia-reperfusion injury in rats. METHODS: One hundred and fifty male Wistar
      rats, weighing 190-210 g, aged 7 wk, were randomly divided into melatonin
      exposure group, alcohol solvent control group and normal saline control group.
      Rats in the melatonin exposure group received intraperitoneal (IP) melatonin (20
      mg/kg) 30 min before intestinal ischemia-reperfusion (IR), rats in the alcohol
      solvent control group received the same concentration and volume of alcohol, and
      rats in the normal saline control group received the same volume of normal
      saline. Serum samples were collected from each group 0.5, 1, 6, 12, and 24 h
      after intestinal IR. Levels of serum alanine aminotransferase (ALT) and aspartate
      aminotransferase (AST) were measured with an auto-biochemical analyzer. Serum TNF
      alpha was tested by enzyme-linked immunosorbent assay (ELISA). Malondialdehyde
      (MDA) in liver was detected by colorimetric assay. Pathological changes in liver
      and immunohistochemical straining of ICAM-1 were observed under an optical
      microscope. RESULTS: The levels of ALT measured at various time points after
      intestinal IR in the melatonin exposure group were significantly lower than those
      in the other two control groups (P < 0.05). The serum AST levels 12 and 24 h
      after intestinal IR and the ICAM-1 levels (%) 6, 12 and 24 h after intestinal IR
      in the melatonin exposure group were also significantly lower than those in the
      other two control groups (P < 0.05). CONCLUSION: Exotic melatonin can inhibit the
      activity of ALT, AST and TNF-alpha, decrease the accumulation of MDA, and depress
      the expression of ICAM-1 in liver after intestinal IR injury, thus improving the
      liver function.

PMID- 19109876
TI  - Peutz-Jeghers syndrome with small intestinal malignancy and cervical carcinoma.
AB  - We report a case of 30-year-old woman with Peutz-Jeghers syndrome (PJS). Because
      of small intestinal obstruction, she received the small intestinal polypectomy in
      2001, and the pathological diagnosis was Peutz-Jeghers polyp canceration
      (mucinous adenocarcinoma, infiltrating full-thickness of the intestine). The
      patient did not feel uncomfortable after 6 mo of chemotherapy and other
      management. We kept a follow-up study on her and found that she suffered from
      cervical cancer in 2007, with a pathological diagnosis of cervical adenosquamous
      carcinoma.The patient presented with typical features of PJS, but without a
      family history. The PJS accompanied with both small intestinal and cervical
      malignancies has not been reported so far in the world.

PMID- 19109877
TI  - SimHap GUI: an intuitive graphical user interface for genetic association
      analysis.
AB  - BACKGROUND: Researchers wishing to conduct genetic association analysis involving
      single nucleotide polymorphisms (SNPs) or haplotypes are often confronted with
      the lack of user-friendly graphical analysis tools, requiring sophisticated
      statistical and informatics expertise to perform relatively straightforward
      tasks. Tools, such as the SimHap package for the R statistics language, provide
      the necessary statistical operations to conduct sophisticated genetic analysis,
      but lacks a graphical user interface that allows anyone but a professional
      statistician to effectively utilise the tool. RESULTS: We have developed SimHap
      GUI, a cross-platform integrated graphical analysis tool for conducting
      epidemiological, single SNP and haplotype-based association analysis. SimHap GUI
      features a novel workflow interface that guides the user through each logical
      step of the analysis process, making it accessible to both novice and advanced
      users. This tool provides a seamless interface to the SimHap R package, while
      providing enhanced functionality such as sophisticated data checking, automated
      data conversion, and real-time estimations of haplotype simulation progress.
      CONCLUSION: SimHap GUI provides a novel, easy-to-use, cross-platform solution for
      conducting a range of genetic and non-genetic association analyses. This provides
      a free alternative to commercial statistics packages that is specifically
      designed for genetic association analysis.

PMID- 19109878
TI  - Host strain specific sex pheromone variation in Spodoptera frugiperda.
AB  - BACKGROUND: The fall armyworm Spodoptera frugiperda (Lepidoptera; Noctuidae)
      consists of two distinct strains with different host plant preferences for corn
      and rice. To assess whether pheromonal-mediated behavioral isolation accompanies
      the habitat isolation on different host plants, we compared the sex pheromone
      composition among females of the two strains. Pheromone glands were extracted
      with or without injection of pheromone biosynthesis activating neuropeptide
      (PBAN). To assess the mode of inheritance of this variation, we also analyzed the
      pheromone composition of F1 hybrid females. RESULTS: Relative to intra-strain
      variation, the pheromone composition of the two strains differed significantly.
      Corn strain females contained significantly more of the second most abundant
      pheromone compound Z11-16:Ac (m), and significantly less of most other compounds,
      than rice strain females. When females were injected with PBAN before their
      glands were extracted, the differences between the strains were less pronounced
      but still statistically significant. The pheromone composition of hybrid females
      showed a maternal inheritance of the major component Z9-14:Ac (M) as well as of
      Z11-16:Ac (m). Most other compounds showed an inheritance indicating genetic
      dominance of the corn strain. The within-strain phenotypic correlations among the
      various components were consistent with their hypothesized biosynthetic pathway,
      and between-strain differences in the correlation structure suggested candidate
      genes that may explain the pheromone differences between the two strains. These
      include Delta9- and Delta11 desaturases, and possibly also a Delta7-desaturase,
      although the latter has not been identified in insects so far. CONCLUSION: The
      two host strains of S. frugiperda produce systematically differing female sex
      pheromone blends. Previously-documented geographic variation in the sexual
      communication of this species did not take strain identity into account, and thus
      may be partly explained by different strain occurrence in different regions. The
      finding of pheromone differences reinforces the possibility of incipient
      reproductive isolation among these strains, previously shown to differ in the
      timing of nocturnal mating activity and host plant use. Finding the genetic basis
      of the pheromone differences, as well as these other biological traits, will help
      to elucidate the role of premating isolation in the continuing differentiation of
      these two strains that may eventually lead to speciation.

PMID- 19109879
TI  - Bilateral blunt carotid artery trauma associated with a double lower thoracic
      spine fracture: a case report and review of the literature.
AB  - BACKGROUND: A 26 year old female suffering from a double fracture of the lower
      thoracic spine, as a result of a car accident, was referred to the Spine Unit of
      our Department. No neurological deficit was detected during clinical examination.
      Due to the fracture's instability, posterior stabilization was performed. CASE
      PRESENTATION: Postoperatively, the patient presented a decrease in Glasgow Coma
      Scale (GCS) combined with motor and sensory deficit from the right upper and
      lower extremities. Cerebral ischemia was diagnosed, secondary to distal emboli
      from the right and left internal carotid arteries bilaterally. CONCLUSION:
      Patients' neurological deficits eventually resolved after conservative treatment
      and anticoagulation therapy.

PMID- 19109880
TI  - Aberrant allele-specific replication, independent of parental origin, in blood
      cells of cancer patients.
AB  - BACKGROUND: Allelic counterparts of biallelically expressed genes display an
      epigenetic symmetry normally manifested by synchronous replication, different
      from genes subjected to monoallelic expression, which normally are characterized
      by an asynchronous mode of replication (well exemplified by the SNRPN imprinted
      locus). Malignancy was documented to be associated with gross modifications in
      the inherent replication-timing coordination between allelic counterparts of
      imprinted genes as well as of biallelically expressed loci. The cancer-related
      allelic replication timing aberrations are non-disease specific and appear in
      peripheral blood cells of cancer patients, including those with solid tumors. As
      such they offer potential blood markers for non-invasive cancer test. The present
      study was aimed to gain some insight into the mechanism leading to the
      replication timing alterations of genes in blood lymphocytes of cancer patients.
      METHODS: Peripheral blood samples derived from patients with prostate cancer were
      chosen to represent the cancerous status, and samples taken from patients with no
      cancer but with benign prostate hyperplasia were used to portray the normal
      status. Fluorescence In Situ Hybridization (FISH) replication assay, applied to
      phytohemagglutinin (PHA)-stimulated blood lymphocytes, was used to evaluate the
      temporal order (either synchronous or asynchronous) of genes in the patients'
      cells. RESULTS: We demonstrated that: (i) the aberrant epigenetic profile, as
      delineated by the cancer status, is a reversible modification, evidenced by our
      ability to restore the normal patterns of replication in three unrelated loci
      (CEN15, SNRPN and RB1) by introducing an archetypical demethylating agent, 5
      azacytidine; (ii) following the rehabilitating effect of demethylation, an
      imprinted gene (SNRPN) retains its original parental imprint; and (iii) the
      choice of an allele between early or late replication in the aberrant
      asynchronous replication, delineated by the cancer status, is not random but is
      independent of the parental origin. CONCLUSION: The non-disease specific aberrant
      epigenetic profile displayed in peripheral blood cells of patients with a solid
      tumour (unlike genetic aberrations) can be reversed, by an epigenetic drug
      applied in vitro, to the normal. It appears that the cancerous status
      differentiates between two allelic counterparts in a non-random manner, but
      independent of the parental origin.

PMID- 19109881
TI  - Networking opportunities for bacteria.
AB  - In this post-genomic era, our capacity to explore biological networks and predict
      network architectures has been greatly expanded, accelerating interest in systems
      biology. Here, we highlight recent systems biology studies in prokaryotes,
      consider the challenges ahead, and suggest opportunities for future studies in
      bacterial models.

PMID- 19109882
TI  - Mitochondrial beta-barrel proteins, an exclusive club?

PMID- 19109884
TI  - Necroptosis: a specialized pathway of programmed necrosis.
AB  - Necrosis is often viewed as an accidental and unregulated cellular event.
      However, accumulating evidence suggests that necrosis, like apoptosis, can be
      executed by regulated mechanisms. Hitomi et al. (2008) now describe an extensive
      network of genes that mediate a form of programmed necrosis called necroptosis.

PMID- 19109885
TI  - The long and short of membrane fission.
AB  - During membrane fission, the GTPase dynamin forms helical assemblies at the neck
      of membrane buds. Although it has been proposed that fission results from the
      constriction of the dynamin helix, new work by Bashkirov et al. (2008) and
      Pucadyil and Schmid (2008) unexpectedly shows that helix disassembly is also
      necessary for membrane fission.

PMID- 19109886
TI  - Mitofusin 2 builds a bridge between ER and mitochondria.
AB  - Mutations in mitofusin 2 (MFN2), a dynamin-like GTPase required for mitochondrial
      fusion, cause the peripheral neuropathy Charcot-Marie-Tooth type 2A. In a recent
      report in Nature, de Brito and Scorrano (2008) demonstrate a new function of MFN2
      tethering the endoplasmic reticulum and mitochondria to control the efficiency of
      mitochondrial uptake of Ca2+ ions.

PMID- 19109887
TI  - DNA Cytosine demethylation: are we getting close?
AB  - Whether 5-methylcytosine (meC) can be enzymatically removed from vertebrate DNA
      has been the subject of extensive study and also some controversy. Rai et al.
      (2008) now report that cytosine demethylation can be accomplished in a one-cell
      zebrafish embryo by the combined action of a cytidine deaminase and a thymine DNA
      glycosylase.

PMID- 19109888
TI  - A charged performance by gp17 in viral packaging.
AB  - Packaging of viral genomes into virus capsids requires powerful motors to
      overcome the repulsive force that builds as the nucleic acids are compressed.
      Through structural analyses of the T4 bacteriophage packaging motor gp17, Sun et
      al. (2008) now propose a packaging mechanism in which electrostatic forces cause
      the motor to alternate between tensed and relaxed conformational states.

PMID- 19109889
TI  - Here comes the sun: recognition of UV-damaged DNA.
AB  - The first step in the repair of DNA damage is lesion detection. In this issue,
      Scrima et al. (2008) report the structure of the complex of DNA Damage-Binding
      Protein 1 (DDB1) and DDB2 bound to a DNA photodimer, providing critical insight
      into the repair of DNA damage caused by ultraviolet light.

PMID- 19109890
TI  - Tracing the retrograde route in protein trafficking.
AB  - Retrograde transport, in which proteins and lipids are shuttled between endosomes
      and biosynthetic/secretory compartments such as the Golgi apparatus, is crucial
      for a diverse range of cellular functions. Mechanistic studies that explore the
      molecular machinery involved in this retrograde trafficking route are shedding
      light on the functions of transport proteins and are providing fresh insights
      into possible new therapeutic directions.

PMID- 19109891
TI  - An ankyrin-based mechanism for functional organization of dystrophin and
      dystroglycan.
AB  - beta-dystroglycan (DG) and the dystrophin-glycoprotein complex (DGC) are
      localized at costameres and neuromuscular junctions in the sarcolemma of skeletal
      muscle. We present evidence for an ankyrin-based mechanism for sarcolemmal
      localization of dystrophin and beta-DG. Dystrophin binds ankyrin-B and ankyrin-G,
      while beta-DG binds ankyrin-G. Dystrophin and beta-DG require ankyrin-G for
      retention at costameres but not delivery to the sarcolemma. Dystrophin and beta
      DG remain intracellular in ankyrin-B-depleted muscle, where beta-DG accumulates
      in a juxta-TGN compartment. The neuromuscular junction requires ankyrin-B for
      localization of dystrophin/utrophin and beta-DG and for maintenance of its
      postnatal morphology. A Becker muscular dystrophy mutation reduces ankyrin
      binding and impairs sarcolemmal localization of dystrophin-Dp71. Ankyrin-B also
      binds to dynactin-4, a dynactin subunit. Dynactin-4 and a subset of microtubules
      disappear from sarcolemmal sites in ankyrin-B-depleted muscle. Ankyrin-B thus is
      an adaptor required for sarcolemmal localization of dystrophin, as well as
      dynactin-4.

PMID- 19109892
TI  - DNA demethylation in zebrafish involves the coupling of a deaminase, a
      glycosylase, and gadd45.
AB  - Evidence for active DNA demethylation in vertebrates is accumulating, but the
      mechanisms and enzymes remain unclear. Using zebrafish embryos we provide
      evidence for 5-methylcytosine (5-meC) removal in vivo via the coupling of a 5-meC
      deaminase (AID, which converts 5-meC to thymine) and a G:T mismatch-specific
      thymine glycosylase (Mbd4). The injection of methylated DNA into embryos induced
      a potent DNA demethylation activity, which was attenuated by depletion of AID or
      the non enzymatic factor Gadd45. Remarkably, overexpression of the
      deaminase/glycosylase pair AID/Mbd4 in vivo caused demethylation of the bulk
      genome and injected methylated DNA fragments, likely involving a G:T
      intermediate. Furthermore, AID or Mbd4 knockdown caused the remethylation of a
      set of common genes. Finally, Gadd45 promoted demethylation and enhanced
      functional interactions between deaminase/glycosylase pairs. Our results provide
      evidence for a coupled mechanism of 5-meC demethylation, whereby AID deaminates 5
      meC, followed by thymine base excision by Mbd4, promoted by Gadd45.

PMID- 19109893
TI  - Structural basis of UV DNA-damage recognition by the DDB1-DDB2 complex.
AB  - Ultraviolet (UV) light-induced pyrimidine photodimers are repaired by the
      nucleotide excision repair pathway. Photolesions have biophysical parameters
      closely resembling undamaged DNA, impeding discovery through damage surveillance
      proteins. The DDB1-DDB2 complex serves in the initial detection of UV lesions in
      vivo. Here we present the structures of the DDB1-DDB2 complex alone and bound to
      DNA containing either a 6-4 pyrimidine-pyrimidone photodimer (6-4PP) lesion or an
      abasic site. The structure shows that the lesion is held exclusively by the WD40
      domain of DDB2. A DDB2 hairpin inserts into the minor groove, extrudes the
      photodimer into a binding pocket, and kinks the duplex by approximately 40
      degrees. The tightly localized probing of the photolesions, combined with
      proofreading in the photodimer pocket, enables DDB2 to detect lesions refractory
      to detection by other damage surveillance proteins. The structure provides
      insights into damage recognition in chromatin and suggests a mechanism by which
      the DDB1-associated CUL4 ubiquitin ligase targets proteins surrounding the site
      of damage.

PMID- 19109894
TI  - Dynamic regulation of alternative splicing by silencers that modulate 5' splice
      site competition.
AB  - Alternative splicing makes a major contribution to proteomic diversity in higher
      eukaryotes with approximately 70% of genes encoding two or more isoforms. In most
      cases, the molecular mechanisms responsible for splice site choice remain poorly
      understood. Here, we used a randomization-selection approach in vitro to identify
      sequence elements that could silence a proximal strong 5' splice site located
      downstream of a weakened 5' splice site. We recovered two exonic and four
      intronic motifs that effectively silenced the proximal 5' splice site both in
      vitro and in vivo. Surprisingly, silencing was only observed in the presence of
      the competing upstream 5' splice site. Biochemical evidence strongly suggests
      that the silencing motifs function by altering the U1 snRNP/5' splice site
      complex in a manner that impairs commitment to specific splice site pairing. The
      data indicate that perturbations of non-rate-limiting step(s) in splicing can
      lead to dramatic shifts in splice site choice.

PMID- 19109895
TI  - Translation initiation on mammalian mRNAs with structured 5'UTRs requires DExH
      box protein DHX29.
AB  - Eukaryotic protein synthesis begins with assembly of 48S initiation complexes at
      the initiation codon of mRNA, which requires at least seven initiation factors
      (eIFs). First, 43S preinitiation complexes comprising 40S ribosomal subunits,
      eIFs 3, 2, 1, and 1A, and tRNA(Met)(i) attach to the 5'-proximal region of mRNA
      and then scan along the 5' untranslated region (5'UTR) to the initiation codon.
      Attachment of 43S complexes is mediated by three other eIFs, 4F, 4A, and 4B,
      which cooperatively unwind the cap-proximal region of mRNA and later also assist
      43S complexes during scanning. We now report that these seven eIFs are not
      sufficient for efficient 48S complex formation on mRNAs with highly structured
      5'UTRs, and that this process requires the DExH-box protein DHX29. DHX29 binds
      40S subunits and hydrolyzes ATP, GTP, UTP, and CTP. NTP hydrolysis by DHX29 is
      strongly stimulated by 43S complexes and is required for DHX29's activity in
      promoting 48S complex formation.

PMID- 19109896
TI  - The structure of the phage T4 DNA packaging motor suggests a mechanism dependent
      on electrostatic forces.
AB  - Viral genomes are packaged into "procapsids" by powerful molecular motors. We
      report the crystal structure of the DNA packaging motor protein, gene product 17
      (gp17), in bacteriophage T4. The structure consists of an N-terminal ATPase
      domain, which provides energy for compacting DNA, and a C-terminal nuclease
      domain, which terminates packaging. We show that another function of the C
      terminal domain is to translocate the genome into the procapsid. The two domains
      are in close contact in the crystal structure, representing a "tensed state." A
      cryo-electron microscopy reconstruction of the T4 procapsid complexed with gp17
      shows that the packaging motor is a pentamer and that the domains within each
      monomer are spatially separated, representing a "relaxed state." These structures
      suggest a mechanism, supported by mutational and other data, in which
      electrostatic forces drive the DNA packaging by alternating between tensed and
      relaxed states. Similar mechanisms may occur in other molecular motors.

PMID- 19109897
TI  - Capture of authentic embryonic stem cells from rat blastocysts.
AB  - Embryonic stem (ES) cells have been available from inbred mice since 1981 but
      have not been validated for other rodents. Failure to establish ES cells from a
      range of mammals challenges the identity of cultivated stem cells and our
      understanding of the pluripotent state. Here we investigated derivation of ES
      cells from the rat. We applied molecularly defined conditions designed to shield
      the ground state of authentic pluripotency from inductive differentiation
      stimuli. Undifferentiated cell lines developed that exhibited diagnostic features
      of ES cells including colonization of multiple tissues in viable chimeras.
      Definitive ES cell status was established by transmission of the cell line genome
      to offspring. Derivation of germline-competent ES cells from the rat paves the
      way to targeted genetic manipulation in this valuable biomedical model species.
      Rat ES cells will also provide a refined test-bed for functional evaluation of
      pluripotent stem cell-derived tissue repair and regeneration.

PMID- 19109898
TI  - Germline competent embryonic stem cells derived from rat blastocysts.
AB  - Rats have important advantages over mice as an experimental system for
      physiological and pharmacological investigations. The lack of rat embryonic stem
      (ES) cells has restricted the availability of transgenic technologies to create
      genetic models in this species. Here, we show that rat ES cells can be
      efficiently derived, propagated, and genetically manipulated in the presence of
      small molecules that specifically inhibit GSK3, MEK, and FGF receptor tyrosine
      kinases. These rat ES cells express pluripotency markers and retain the capacity
      to differentiate into derivatives of all three germ layers. Most importantly,
      they can produce high rates of chimerism when reintroduced into early stage
      embryos and can transmit through the germline. Establishment of authentic rat ES
      cells will make possible sophisticated genetic manipulation to create models for
      the study of human diseases.

PMID- 19109899
TI  - Identification of a molecular signaling network that regulates a cellular
      necrotic cell death pathway.
AB  - Stimulation of death receptors by agonists such as FasL and TNFalpha activates
      apoptotic cell death in apoptotic-competent conditions or a type of necrotic cell
      death dependent on RIP1 kinase, termed necroptosis, in apoptotic-deficient
      conditions. In a genome-wide siRNA screen for regulators of necroptosis, we
      identify a set of 432 genes that regulate necroptosis, a subset of 32 genes that
      act downstream and/or as regulators of RIP1 kinase, 32 genes required for death
      receptor-mediated apoptosis, and 7 genes involved in both necroptosis and
      apoptosis. We show that the expression of subsets of the 432 genes is enriched in
      the immune and nervous systems, and cellular sensitivity to necroptosis is
      regulated by an extensive signaling network mediating innate immunity.
      Interestingly, Bmf, a BH3-only Bcl-2 family member, is required for death
      receptor-induced necroptosis. Our study defines a cellular signaling network that
      regulates necroptosis and the molecular bifurcation that controls apoptosis and
      necroptosis.

PMID- 19109900
TI  - Translational control of BACE1 may go awry in Alzheimer's disease.
AB  - Our understanding of the mechanisms whereby BACE1, the aspartyl protease required
      for the initial cleavage of APP to generate amyloid-beta (Abeta), is regulated in
      Alzheimer's disease (AD) remains incomplete. In this issue of Neuron, O'Connor
      and coworkers show how energy deprivation, a potential risk factor in AD,
      triggers the phosphorylation of the translation initiation factor eIF2alpha to
      elevate the translation efficiency of a set of stress-related transcripts,
      including that of BACE1, and increases the level of BACE1, thereby accelerating
      amyloidogenesis.

PMID- 19109901
TI  - The right period for a Siesta.
AB  - Drosophila melanogaster has a broad geographic range. Daily activity in this
      species exhibits seasonality such that midday rest expands on long warm days,
      possibly to avoid desiccation. Comparative analyses show that temperature
      dependent control of this behavior is partly linked to patterns of per mRNA
      splicing that are absent in Drosophila yakuba, a related species native to warmer
      climates with little seasonal change.

PMID- 19109902
TI  - So many choices: what computational models reveal about decision-making
      mechanisms.
AB  - Is decision making in the brain (a) optimal, (b) stochastic, (c) probabilistic,
      or (d) all of the above? Two papers in this issue of Neuron by Beck et al. and
      Furman and Wang address these questions by constructing model neural circuits
      capable of picking one option given multiple perceptual choices.

PMID- 19109903
TI  - Reversing neurodevelopmental disorders in adults.
AB  - Abnormalities in brain development, thought to be irreversible in adults, have
      long been assumed to underlie the neurological and psychiatric symptoms
      associated with neurodevelopmental disorders. Surprisingly, a number of recent
      animal model studies of neurodevelopmental disorders demonstrate that reversing
      the underlying molecular deficits can result in substantial improvements in
      function even if treatments are started in adulthood. These findings mark a
      paradigmatic change in the way we understand and envision treating
      neurodevelopmental disorders.

PMID- 19109904
TI  - Decoding the epigenetic language of neuronal plasticity.
AB  - Neurons are submitted to an exceptional variety of stimuli and are able to
      convert these into high-order functions, such as storing memories, controlling
      behavior, and governing consciousness. These unique properties are based on the
      highly flexible nature of neurons, a characteristic that can be regulated by the
      complex molecular machinery that controls gene expression. Epigenetic control,
      which largely involves events of chromatin remodeling, appears to be one way in
      which transcriptional regulation of gene expression can be modified in neurons.
      This review will focus on how epigenetic control in the mature nervous system may
      guide dynamic plasticity processes and long-lasting cellular neuronal responses.
      We outline the molecular pathways underlying chromatin transitions, propose the
      presence of an "epigenetic indexing code," and discuss how central findings
      accumulating at an exponential pace in the field of epigenetics are conceptually
      changing our perspective of adult brain function.

PMID- 19109905
TI  - Control of presynaptic function by a persistent Na(+) current.
AB  - Little is known about ion channels that regulate the graded, subthreshold
      properties of nerve terminals. Using the calyx of Held, we demonstrate here a
      large presynaptic persistent Na(+) current with unusually hyperpolarized
      activation voltage. This feature allowed the current to determine both the
      resting potential and resting conductance of the nerve terminal. Calyces express
      presynaptic glycine receptors whose activation depolarizes the synapse. We found
      that activation of the persistent Na(+) current was an essential component in the
      response to glycine. This Na(+) current originated at or very close to the
      terminal and was sustained even after trains of large spike-like depolarizations.
      Because Na(+) channels also underlie the presynaptic action potential, we
      conclude that their action both triggers and modulates exocytosis through control
      of presynaptic membrane voltage.

PMID- 19109906
TI  - State-dependent cAMP sensitivity of presynaptic function underlies metaplasticity
      in a hippocampal feedforward inhibitory circuit.
AB  - At hippocampal mossy fiber (MF)-st. lucidum interneuron (SLIN) synapses, mGluR7
      serves as a metaplastic switch controlling bidirectional plasticity. mGluR7
      activation during high-frequency stimulation (HFS) triggers presynaptic LTD due
      to persistent P/Q-type Ca(2+) channel inhibition. However, following mGluR7
      internalization HFS produces presynaptic LTP. Surprisingly, LTP is not a simple
      molecular reversal of Ca(2+) channel depression. Rather, mGluR7
      activation/internalization controls plasticity polarity by gating cAMP
      sensitivity of release. While naive surface mGluR7 expressing MF-SLIN synapses
      are insensitive to cAMP elevation, synapses that have internalized mGluR7
      robustly potentiate following cAMP increases. Moreover, MF-SLIN LTP requires
      adenylate cyclase (AC) and protein kinase A (PKA) activities. We also discovered
      an association between mGluR7 and RIM1alpha, an active zone molecule required for
      AC/PKA-dependent presynaptic LTP. Importantly, the mGluR7-RIM1alpha interaction
      is regulated by mGluR7 activation, and mice lacking RIM1alpha are deficient in MF
      SLIN LTP. We conclude that state-dependent cAMP sensitivity controlled by mGluR7
      RIM1alpha interactions underlies MF-SLIN metaplasticity.

PMID- 19109908
TI  - Genomic anatomy of the hippocampus.
AB  - Availability of genome-scale in situ hybridization data allows systematic
      analysis of genetic neuroanatomical architecture. Within the hippocampus,
      electrophysiology and lesion and imaging studies demonstrate functional
      heterogeneity along the septotemporal axis, although precise underlying circuitry
      and molecular substrates remain uncharacterized. Application of unbiased
      statistical component analyses to genome-scale hippocampal gene expression data
      revealed robust septotemporal molecular heterogeneity, leading to the
      identification of a large cohort of genes with robust regionalized hippocampal
      expression. Manual mapping of heterogeneous CA3 pyramidal neuron expression
      patterns demonstrates an unexpectedly complex molecular parcellation into a
      relatively coherent set of nine expression domains in the septal/temporal and
      proximal/distal axes with reciprocal, nonoverlapping boundaries. Unique
      combinatorial profiles of adhesion molecules within these domains suggest
      corresponding differential connectivity, which is demonstrated for CA3
      projections to the lateral septum using retrograde labeling. This complex,
      discrete molecular architecture provides a novel paradigm for predicting
      functional differentiation across the full septotemporal extent of the
      hippocampus.

PMID- 19109907
TI  - Phosphorylation of the translation initiation factor eIF2alpha increases BACE1
      levels and promotes amyloidogenesis.
AB  - beta-site APP cleaving enzyme-1 (BACE1), the rate-limiting enzyme for beta
      amyloid (Abeta) production, is elevated in Alzheimer's disease (AD). Here, we
      show that energy deprivation induces phosphorylation of the translation
      initiation factor eIF2alpha (eIF2alpha-P), which increases the translation of
      BACE1. Salubrinal, an inhibitor of eIF2alpha-P phosphatase PP1c, directly
      increases BACE1 and elevates Abeta production in primary neurons. Preventing
      eIF2alpha phosphorylation by transfection with constitutively active PP1c
      regulatory subunit, dominant-negative eIF2alpha kinase PERK, or PERK inhibitor
      P58(IPK) blocks the energy-deprivation-induced BACE1 increase. Furthermore,
      chronic treatment of aged Tg2576 mice with energy inhibitors increases levels of
      eIF2alpha-P, BACE1, Abeta, and amyloid plaques. Importantly, eIF2alpha-P and
      BACE1 are elevated in aggressive plaque-forming 5XFAD transgenic mice, and BACE1,
      eIF2alpha-P, and amyloid load are correlated in humans with AD. These results
      strongly suggest that eIF2alpha phosphorylation increases BACE1 levels and causes
      Abeta overproduction, which could be an early, initiating molecular mechanism in
      sporadic AD.

PMID- 19109909
TI  - Genome-wide analysis of MEF2 transcriptional program reveals synaptic target
      genes and neuronal activity-dependent polyadenylation site selection.
AB  - Although many transcription factors are known to control important aspects of
      neural development, the genome-wide programs that are directly regulated by these
      factors are not known. We have characterized the genetic program that is
      activated by MEF2, a key regulator of activity-dependent synapse development.
      These MEF2 target genes have diverse functions at synapses, revealing a broad
      role for MEF2 in synapse development. Several of the MEF2 targets are mutated in
      human neurological disorders including epilepsy and autism spectrum disorders,
      suggesting that these disorders may be caused by disruption of an activity
      dependent gene program that controls synapse development. Our analyses also
      reveal that neuronal activity promotes alternative polyadenylation site usage at
      many of the MEF2 target genes, leading to the production of truncated mRNAs that
      may have different functions than their full-length counterparts. Taken together,
      these analyses suggest that the ubiquitously expressed transcription factor MEF2
      regulates an intricate transcriptional program in neurons that controls synapse
      development.

PMID- 19109910
TI  - Specification of motor axon trajectory by ephrin-B:EphB signaling: symmetrical
      control of axonal patterning in the developing limb.
AB  - Studies of the innervation of limb muscles by spinal motor neurons have helped to
      define mechanisms by which axons establish trajectories to their targets. Related
      motor axons select dorsal or ventral pathways at the base of the limb, raising
      the question of how these alternate trajectories are specified. EphA signaling
      has been proposed to control the dorsal trajectory of motor axons in conjunction
      with other signaling systems, although the respective contributions of each
      system to motor axon guidance are unclear. We show that the expression of EphB
      receptors by motor axons, and ephrin-B ligands by limb mesenchymal cells, directs
      the ventral trajectory of motor axons. Our findings reveal symmetry in the
      molecular strategies that establish this aspect of nerve-muscle connectivity. The
      involvement of ephrin:Eph signaling in guiding both sets of motor axons raises
      the possibility that other signaling systems function primarily to refine or
      modulate a core Eph signaling program.

PMID- 19109911
TI  - Natural variation in the splice site strength of a clock gene and species
      specific thermal adaptation.
AB  - We show that multiple suboptimal splice sites underlie the thermal-sensitive
      splicing of the period (per) 3'-terminal intron (dmpi8) from D. melanogaster,
      enabling this species to prolong its midday "siesta," a mechanism that likely
      diminishes the deleterious effects of heat during the longer summer days in
      temperate climates. In D. yakuba and D. santomea, which have a more ancestral
      distribution indigenous to Afro-equatorial regions wherein day length and
      temperature exhibit little fluctuation throughout the year, the splicing
      efficiencies of their per 3'-terminal introns do not exhibit thermal calibration,
      consistent with the little effect of temperature on the daily distribution of
      activity in these species. We propose that the weak splice sites on dmpi8
      underlie a mechanism that facilitated the acclimation of the widely colonized D.
      melanogaster (and possibly D. simulans) to temperate climates and that natural
      selection operating at the level of splicing signals plays an important role in
      the thermal adaptation of life forms.

PMID- 19109912
TI  - Mice with a "monoclonal nose": perturbations in an olfactory map impair odor
      discrimination.
AB  - We have altered the neural representation of odors in the brain by generating a
      mouse with a "monoclonal nose" in which greater than 95% of the sensory neurons
      express a single odorant receptor, M71. As a consequence, the frequency of
      sensory neurons expressing endogenous receptor genes is reduced 20-fold. We
      observe that these mice can smell, but odor discrimination and performance in
      associative olfactory learning tasks are impaired. However, these mice cannot
      detect the M71 ligand acetophenone despite the observation that virtually all
      sensory neurons and glomeruli are activated by this odor. The M71 transgenic mice
      readily detect other odors in the presence of acetophenone. These observations
      have implications for how receptor activation in the periphery is represented in
      the brain and how these representations encode odors.

PMID- 19109913
TI  - Role of glutamate autoreceptors at hippocampal mossy fiber synapses.
AB  - Presynaptic autoreceptors modulate transmitter release at many synapses. At the
      mossy fiber to CA3 pyramidal cell (mf-CA3) synapse, two types of glutamatergic
      autoreceptors have been identified: transmitter release is reportedly suppressed
      by metabotropic glutamate receptors (mGluRs) and augmented by kainate receptors
      (KARs). However, the net effect of these autoreceptors when activated by
      endogenous glutamate is unknown. Here, we show that during low-frequency mossy
      fiber stimulation, glutamate acting through presynaptic mGluRs substantially
      suppresses transmitter release. However, using similar recording conditions, we
      find that presynaptic KARs are insufficient to facilitate transmitter release
      over a wide range of mossy fiber stimulus frequencies, indicating that the
      uniquely robust mf-CA3 short-term plasticity is KAR independent. Furthermore, we
      report that actions generally attributed to presynaptic KARs are likely due to
      activation of recurrent CA3 network activity. Thus, negative feedback via
      presynaptic mGluRs is the dominant mode of glutamatergic autoregulation at the mf
      CA3 synapse.

PMID- 19109914
TI  - Metabotropic glutamate receptor-mediated LTD involves two interacting Ca(2+)
      sensors, NCS-1 and PICK1.
AB  - There are two major forms of long-term depression (LTD) of synaptic transmission
      in the central nervous system that require activation of either N-methyl-D
      aspartate receptors (NMDARs) or metabotropic glutamate receptors (mGluRs). In
      synapses in the perirhinal cortex, we have directly compared the Ca(2+) signaling
      mechanisms involved in NMDAR-LTD and mGluR-LTD. While both forms of LTD involve
      Ca(2+) release from intracellular stores, the Ca(2+) sensors involved are
      different; NMDAR-LTD involves calmodulin, while mGluR-LTD involves the neuronal
      Ca(2+) sensor (NCS) protein NCS-1. In addition, there is a specific requirement
      for IP3 and PKC, as well as protein interacting with C kinase (PICK-1) in mGluR
      LTD. NCS-1 binds directly to PICK1 via its BAR domain in a Ca(2+)-dependent
      manner. Furthermore, the NCS-1-PICK1 association is stimulated by activation of
      mGluRs, but not NMDARs, and introduction of a PICK1 BAR domain fusion protein
      specifically blocks mGluR-LTD. Thus, NCS-1 plays a distinct role in mGluR-LTD.

PMID- 19109915
TI  - Emergent properties of tactile scenes selectively activate barrel cortex neurons.
AB  - Rats discriminate objects by scanning their surface with the facial vibrissae,
      producing spatiotemporally complex sequences of tactile contacts. The way in
      which the somatosensory cortex responds to these complex multivibrissal stimuli
      has not been explored. It is unclear yet whether contextual information from
      across the entire whisker pad influences cortical responses. Here, we delivered
      tactile stimuli to the rat vibrissae using a new 24 whisker stimulator. We tested
      sequences of rostrocaudal whisker deflections that generate multivibrissal motion
      patterns in different directions across the mystacial pad, allowing to
      disambiguate local from global sensory integration. Unitary electrophysiological
      recordings from different layers of the barrel cortex showed that a majority of
      neurons has direction selectivity for the multivibrissal stimulus. The
      selectivity resulted from nonlinear integration of responses across the mystacial
      pad. Our results indicate that the system extracts collective properties of a
      tactile scene.

PMID- 19109916
TI  - Matching categorical object representations in inferior temporal cortex of man
      and monkey.
AB  - Inferior temporal (IT) object representations have been intensively studied in
      monkeys and humans, but representations of the same particular objects have never
      been compared between the species. Moreover, IT's role in categorization is not
      well understood. Here, we presented monkeys and humans with the same images of
      real-world objects and measured the IT response pattern elicited by each image.
      In order to relate the representations between the species and to computational
      models, we compare response-pattern dissimilarity matrices. IT response patterns
      form category clusters, which match between man and monkey. The clusters
      correspond to animate and inanimate objects; within the animate objects, faces
      and bodies form subclusters. Within each category, IT distinguishes individual
      exemplars, and the within-category exemplar similarities also match between the
      species. Our findings suggest that primate IT across species may host a common
      code, which combines a categorical and a continuous representation of objects.

PMID- 19109917
TI  - Probabilistic population codes for Bayesian decision making.
AB  - When making a decision, one must first accumulate evidence, often over time, and
      then select the appropriate action. Here, we present a neural model of decision
      making that can perform both evidence accumulation and action selection
      optimally. More specifically, we show that, given a Poisson-like distribution of
      spike counts, biological neural networks can accumulate evidence without loss of
      information through linear integration of neural activity and can select the most
      likely action through attractor dynamics. This holds for arbitrary correlations,
      any tuning curves, continuous and discrete variables, and sensory evidence whose
      reliability varies over time. Our model predicts that the neurons in the lateral
      intraparietal cortex involved in evidence accumulation encode, on every trial, a
      probability distribution which predicts the animal's performance. We present
      experimental evidence consistent with this prediction and discuss other
      predictions applicable to more general settings.

PMID- 19109918
TI  - Similarity effect and optimal control of multiple-choice decision making.
AB  - Decision making with several choice options is central to cognition. To elucidate
      the neural mechanisms of such decisions, we investigated a recurrent cortical
      circuit model in which fluctuating spiking neural dynamics underlie trial-by
      trial stochastic decisions. The model encodes a continuous analog stimulus
      feature and is thus applicable to multiple-choice decisions. Importantly, the
      continuous network captures similarity between alternatives and possible overlaps
      in their neural representation. Model simulations accounted for behavioral as
      well as single-unit neurophysiological data from a recent monkey experiment and
      revealed testable predictions about the patterns of error rate as a function of
      the similarity between the correct and actual choices. We also found that the
      similarity and number of options affect speed and accuracy of responses. A
      mechanism is proposed for flexible control of speed-accuracy tradeoff, based on a
      simple top-down signal to the decision circuit that may vary nonmonotonically
      with the number of choice alternatives.

PMID- 19109920
TI  - Antibody Fab display system that can perform open-sandwich ELISA.
AB  - Previously, immunological detection of small haptens or peptides was only
      possible in a competitive format, which needed competitor antigen either labeled
      by a reporter or attached to a carrier protein. Beside this, open-sandwich
      immunoassay (OS-IA) is a simple but powerful immunoassay that can
      noncompetitively determine monovalent antigen concentration by measuring the
      antigen-dependent increase in V(H)/V(L) interaction of an antibody. However, the
      procedure to obtain suitable assay reagents for OS-IA for a target antigen has
      not been straightforward because of the lack of easy-to-use antibody
      selection/manipulation methods. Here we devise a new Fab antibody phage display
      system that is useful for rapidly evaluating and selecting suitable antibody Fv
      fragments to OS-IA. The system is based on a phagemid vector in which two
      identical restriction sites were incorporated into both ends of a human constant
      region domain. After selection of the M13 phage displaying a Fab fragment, the
      vector can be easily converted to the vector that can simultaneously produce the
      V(H)-displaying phage and the light chain in the culture supernatant, which can
      be directly used for OS-ELISA. The successful results of model selection as well
      as conversion to OS format show the potential in developing various OS-IA for
      clinically and environmentally important targets.

PMID- 19109919
TI  - Value-based modulations in human visual cortex.
AB  - Economists and cognitive psychologists have long known that prior rewards bias
      decision making in favor of options with high expected value. Accordingly, value
      modulates the activity of sensorimotor neurons involved in initiating movements
      toward one of two competing decision alternatives. However, little is known about
      how value influences the acquisition and representation of incoming sensory
      information or about the neural mechanisms that track the relative value of each
      available stimulus to guide behavior. Here, fMRI revealed value-related
      modulations throughout spatially selective areas of the human visual system in
      the absence of overt saccadic responses (including in V1). These modulations were
      primarily associated with the reward history of each stimulus and not to self
      reported estimates of stimulus value. Finally, subregions of frontal and parietal
      cortex represent the differential value of competing alternatives and may provide
      signals to bias spatially selective visual areas in favor of more valuable
      stimuli.

PMID- 19109921
TI  - Genotyping of single nucleotide polymorphisms using base-quenched probe: a method
      does not invariably depend on the deoxyguanosine nucleotide.
AB  - Most available methods for detecting single nucleotide polymorphisms (SNPs) are
      based principally on the system that can produce an increased fluorescence signal
      during hybridization. In the current study, we demonstrate a method of base
      quenched probe for polymerase chain reaction (PCR) genotyping that requires only
      a pair of primers and one fluorescent probe and does not invariably depend on the
      deoxyguanosine nucleotide. This method further exploits the phenomenon of
      fluorescence quenching of fluorescent-labeled probe during hybridization to its
      complementary target gene's sequence. 6-Carboxyfluorescein (FAM) can be directly
      conjugated to a base of either adenine (A), thymine (T), cytosine (C), or guanine
      (G), referred to as A-, T-, C-, or G-quenched probe, respectively, at either the
      5' or 3' end. For describing the method in detail, we chose apolipoprotein M
      (apoM) as a target gene in the current study. DNA sequencing analyses validated
      that all four types of base-quenched probes could provide unbiased genotyping
      results (K = 1, P = 0.000), although the maximum speed of fluorescence increase,
      max(dF/dT), when using the G-quenched probe method, was approximately twofold
      lower than the others (P < 0.0001). Moreover, we applied this method to detect
      another seven SNPs in the genomes of phospholipase A2, monocyte chemoattractant
      protein 1 (MCP1), and l-ficolin, further confirming our method. It is concluded
      that this method is precise, simple, and economic as well as suitable for large
      scale genotyping studies.

PMID- 19109922
TI  - A fluorescence resonance energy transfer-based approach for investigating late
      endosome-lysosome retrograde fusion events.
AB  - Traditionally, lysosomes have been considered to be a terminal endocytic
      compartment. Recent studies suggest that lysosomes are quite dynamic, being able
      to fuse with other late endocytic compartments as well as with the plasma
      membrane. Here we describe a quantitative fluorescence energy transfer (FRET)
      based method for assessing rates of retrograde fusion between terminal lysosomes
      and late endosomes in living cells. Late endosomes were specifically labeled with
      800-nm latex beads that were conjugated with streptavidin and Alexa Fluor 555
      (FRET donor). Terminal lysosomes were specifically labeled with 10,000-MW dextran
      polymers conjugated with biotin and Alexa Fluor 647 (FRET acceptor). Following
      late endosome-lysosome fusion, the strong binding affinity between streptavidin
      and biotin brought the donor and acceptor fluorophore molecules into close
      proximity, thereby facilitating the appearance of a FRET emission signal. Because
      apparent size restrictions in the endocytic pathway do not permit endocytosed
      latex beads from reaching terminal lysosomes in an anterograde fashion, the
      appearance of the FRET signal is consistent with retrograde transport of
      lysosomal cargo back to late endosomes. We assessed the efficiency of this
      transport step in fibroblasts affected by different lysosome storage disorders
      Niemann-Pick type C, mucolipidosis type IV, and Sandhoff's disease, all of which
      have a similar lysosomal lipid accumulation phenotype. We report here, for the
      first time, that these disorders can be distinguished by their rate of transfer
      of lysosome cargos to late endosomes, and we discuss the implications of these
      findings for developing new therapeutic strategies.

PMID- 19109923
TI  - Comparative analysis of oligosaccharide specificities of fucose-specific lectins
      from Aspergillus oryzae and Aleuria aurantia using frontal affinity
      chromatography.
AB  - Aleuria aurantia lectin (AAL) is widely used to estimate the extent of alpha1,6
      fucosylated oligosaccharides and to fractionate glycoproteins for the detection
      of specific biomarkers for developmental antigens. Our previous studies have
      shown that Aspergillus oryzae lectin (AOL) reflects the extent of alpha1,6
      fucosylation more clearly than AAL. However, the subtle specificities of these
      lectins to fucose linked to oligosaccharides through the 2-, 3-, 4-, or 6
      position remain unclear, because large amounts of oligosaccharides are required
      for the systematic comparative analysis using surface plasmon resonance. Here we
      show a direct comparison of the dissociation constants (K(d)) of AOL and AAL
      using 113 pyridylaminated oligosaccharides with frontal affinity chromatography.
      As a result, AOL showed a similar specificity as AAL in terms of the high
      affinity for alpha1,6-fucosylated oligosaccharides, for smaller fucosylated
      oligosaccharides, and for oligosaccharides fucosylated at the reducing terminal
      core GlcNAc. On the other hand, AOL showed 2.9-6.2 times higher affinity
      constants (K(a)) for alpha1,6-fucosylated oligosaccharides than AAL and only AAL
      additionally recognized oligosaccharides which were alpha1,3-fucosylated at the
      reducing terminal GlcNAc. These results explain why AOL reflects the extent of
      alpha1,6-fucosylation on glycoproteins more clearly than AAL. This systematic
      comparative analysis made from a quantitative viewpoint enabled a clear physical
      interpretation of these fucose-specific lectins with multivalent fucose-binding
      sites.

PMID- 19109924
TI  - Atomic force microscopy differentiates discrete size distributions between
      membrane protein containing and empty nanolipoprotein particles.
AB  - To better understand the incorporation of membrane proteins into discoidal
      nanolipoprotein particles (NLPs) we have used atomic force microscopy (AFM) to
      image and analyze NLPs assembled in the presence of bacteriorhodopsin (bR),
      lipoprotein E4 n-terminal 22k fragment scaffold and DMPC lipid. The self-assembly
      process produced two distinct NLP populations: those containing inserted bR (bR
      NLPs) and those that did not (empty-NLPs). The bR-NLPs were distinguishable from
      empty-NLPs by an average increase in height of 1.0 nm as measured by AFM.
      Streptavidin binding to biotinylated bR confirmed that the original 1.0 nm height
      increase corresponds to br-NLP incorporation. AFM and ion mobility spectrometry
      (IMS) measurements suggest that NLP size did not vary around a single mean but
      instead there were several subpopulations, which were separated by discrete
      diameters. Interestingly, when bR was present during assembly the diameter
      distribution was shifted to larger particles and the larger particles had a
      greater likelihood of containing bR than smaller particles, suggesting that
      membrane proteins alter the mechanism of NLP assembly.

PMID- 19109925
TI  - Loss of membrane cholesterol influences lysosomal permeability to potassium ions
      and protons.
AB  - Cholesterol is an essential component of lysosomal membranes. In this study, we
      investigated the effects of membrane cholesterol on the permeability of rat liver
      lysosomes to K+ and H+, and the organelle stability. Through the measurements of
      lysosomal beta-hexosaminidase free activity, membrane potential, membrane
      fluidity, intra-lysosomal pH, and lysosomal proton leakage, we established that
      methyl-beta-cyclodextrin (MbetaCD)-produced loss of membrane cholesterol could
      increase the lysosomal permeability to both potassium ions and protons, and
      fluidize the lysosomal membranes. As a result, potassium ions entered the
      lysosomes through K+/H+ exchange, which produced osmotic imbalance across the
      membranes and osmotically destabilized the lysosomes. In addition, treatment of
      the lysosomes with MbetaCD caused leakage of the lysosomal protons and raised the
      intra-lysosomal pH. The results indicate that membrane cholesterol plays
      important roles in the maintenance of the lysosomal limited permeability to K+
      and H+. Loss of this membrane sterol is critical for the organelle acidification
      and stability.

PMID- 19109926
TI  - E. coli HflX interacts with 50S ribosomal subunits in presence of nucleotides.
AB  - HflX is a GTP binding protein of unknown function. Based on the presence of the
      hflX gene in hflA operon, HflX was believed to be involved in the lytic-lysogenic
      decision during phage infection in Escherichia coli. We find that E. coli HflX
      binds 16S and 23S rRNA - the RNA components of 30S and 50S ribosomal subunits.
      Here, using purified ribosomal subunits, we show that HflX specifically interacts
      with the 50S. This finding is in line with the homology of HflX to GTPases
      involved in ribosome biogenesis. However, HflX-50S interaction is not limited to
      a specific nucleotide-bound state of the protein, and the presence of any of the
      nucleotides GTP/GDP/ATP/ADP is sufficient. In this respect, HflX is different
      from other GTPases. While E. coli HflX binds and hydrolyses both ATP and GTP,
      only the GTP hydrolysis activity is stimulated by 50S binding. This work uncovers
      interesting attributes of HflX in ribosome binding.

PMID- 19109927
TI  - Rosiglitazone reverses memory decline and hippocampal glucocorticoid receptor
      down-regulation in an Alzheimer's disease mouse model.
AB  - Clinical trials with rosiglitazone, a potent agonist at peroxisome proliferator
      activated receptor gamma (PPARgamma) suggest an improvement of cognitive function
      in Alzheimer's disease (AD) patients. The mechanisms mediating this potential
      beneficial effect remain to be fully elucidated. In mice overexpressing mutant
      human amyloid precursor protein (hAPP), a model of AD, we found that memory
      impairment in the object recognition test was prevented and also reversed by
      chronic rosiglitazone treatment. Given the possible involvement of glucocorticoid
      receptors (GR) in the actions of PPARgamma-ligands, we studied the effect of
      chronic rosiglitazone treatment on GR levels in the hippocampus of hAPP mice. An
      early down-regulation of GR, not related to elevated plasma corticosterone
      levels, was found in different hippocampal subfields of the transgenic mice and
      this decrease was prevented by rosiglitazone. In parallel with behavioural
      studies, rosiglitazone also normalized GR levels in older animals. This effect
      may contribute to explain the attenuation of memory decline by PPARgamma
      activation in an AD mouse model.

PMID- 19109928
TI  - Skp2 promotes adipocyte differentiation via a p27Kip1-independent mechanism in
      primary mouse embryonic fibroblasts.
AB  - Skp2, the substrate-binding subunit of an SCF ubiquitin ligase complex, is a key
      regulator of cell cycle progression that targets substrates for degradation by
      the 26S proteasome. We have now shown that ablation of Skp2 in primary mouse
      embryonic fibroblasts (MEFs) results both in impairment of adipocyte
      differentiation and in the accumulation of the cyclin-dependent kinase inhibitor
      p27(Kip1), a principal target of the SCF(Skp2) complex. Genetic ablation of
      p27(Kip1) in MEFs promoted both lipid accumulation and adipocyte-specific gene
      expression. However, depletion of p27(Kip1) by adenovirus-mediated RNA
      interference failed to correct the impairment of adipocyte differentiation in
      Skp2(-/-) MEFs. In contrast, troglitazone, a high-affinity ligand for peroxisome
      proliferator-activated receptor gamma (PPARgamma), largely restored lipid
      accumulation and PPARgamma gene expression in Skp2(-/-) MEFs. Our data suggest
      that Skp2 plays an essential role in adipogenesis in MEFs in a manner that is at
      least in part independent of regulation of p27(Kip1) expression.

PMID- 19109929
TI  - Expanding the chemical nature of siRNAs: oxaliplatin as metalation reagent.
AB  - Short interfering RNAs (siRNAs) can down-regulate protein production by site
      specific degradation of mRNA. We here report the in vitro efficiency of three
      siRNAs metalated with oxaliplatin. All siRNAs were selectively platinated in the
      sense strand, and designed to target the AU-rich 3' UTR region of Wnt-5a mRNA
      cloned into a luciferase reporter plasmid. Two of the studied siRNAs reveal
      luciferase protein suppression levels well above 90% when used in nano-molar
      concentrations for both metalated and the corresponding native siRNA. The
      platinated siRNAs were also characterized with respect to thermal melting
      properties, and the number of platinum adducts on the different sense strands
      were determined by MALDI-ToF MS. In all cases, platination was accompanied by a
      decrease in melting temperature. Further, the dominating oxaliplatin metalation
      site was the r(GpG)-adduct. The study indicates that metalation can be used as a
      general strategy to further expand the chemical nature of siRNAs.

PMID- 19109930
TI  - Metabolism of protocatechuic acid influences fatty acid oxidation in rat heart:
      new anti-angina mechanism implication.
AB  - Protocatechuic acid (PA), a structurally typical phenolic acid in danshen, shows
      anti-angina efficacy. But until now, besides scavenging of oxygen free radicals,
      the understanding of its anti-angina mechanism has been limited. In our study,
      based on a novel metabolic route of PA identified in rat heart and its influence
      on fatty acid oxidation (FAO), we proposed a new mechanism for its anti-angina.
      In detail, three metabolites, catechol methylated metabolite, acyl-coenzyme (CoA)
      thioester and glycine conjugation, were identified in rat heart. A novel
      metabolic pathway was confirmed based on several metabolic systems incubated with
      heart mitochondria, cytosol, microsomes and homogenate. Results indicated that PA
      was firstly methylated in microsomes and cytosol, which was regarded as the
      prerequisite step for further metabolism and could be inhibited by tolcapone, and
      then the resulting methylated metabolite (vanillic acid) diffused into
      mitochondria where it was converted into acyl-CoA thioester, in similar with FAO.
      In addition, part of the acyl-CoA thioester was transformed into glycine
      conjugation, a step also localized within mitochondria. Furthermore, based on
      isolated rat heart perfusion, it was found that PA markedly decreased FAO, which
      was shown by higher residual fatty acid level in perfusate (p<0.05) and lower acy
      CoA/CoA ratio in heart (p<0.05). The FAO inhibiting effect of PA could be largely
      reversed by its methylation inhibitor tolcapone, indicating the effect was
      closely related with the identified metabolic pathway of PA in heart. The
      decrease of FAO may switch heart energy substrate preference from fatty acid to
      glucose, which is beneficial for ischemia heart.

PMID- 19109931
TI  - Characterization of Fyn signaling on the age-dependent immuno-modulation on
      traumatic rats.
AB  - Traumatic stress is well characterized to develop immuno-depression in our
      previous report. Here, we provide evidence that adult and aged rats showed
      similar decrease in lymphocyte proliferation and natural killer (NK) cell
      activity. However, compared with beginning recovering from traumatic stress after
      3 day and fully recovered by 7 day in adult rats, aged rats begin the recovery
      phage later than 3 day and do not fully recovered by 7 day. In parallel, Fyn
      expression in cerebral cortex was augmented with the highest level at 3 day of
      trauma in both age groups of rats, although aged rats exhibited lower level than
      the younger cohorts. Immune consequences were consequently modified by
      intracerebroventricular (i.c.v.) injection of Fyn antibody or recombinant
      adenovirus expressing active Fyn. Finally, the increase in Fyn expression was
      converged on ERK1/2 (extracellular signal regulated kinase 1/2) activation. Taken
      together, the data indicated that immunological processes in response to
      traumatic stress was age dependent, Fyn-ERK1/2 signal pathway was required to
      convey the recovery signals.

PMID- 19109932
TI  - Proteomic analysis of cerebrospinal fluid from patients with idiopathic temporal
      lobe epilepsy.
AB  - Proteomic analysis of cerebrospinal fluid (CSF) from patients with temporal lobe
      epilepsy (TLE) and controls was carried out using two-dimensional gel
      electrophoresis followed by liquid chromatography electrospray ionization tandem
      mass spectrometry. Five protein spots showed significant differential expression
      (p<0.05): vitamin D-binding protein (DBP) was elevated in the CSF of TLE patients
      whereas cathepsin D, apolipoprotein J, Fam3c, and superoxide dismutase 1 (SOD1)
      were decreased in the CSF of TLE patients. Additional six protein spots presented
      only in the CSF of epilepsy patients were identified as tetranectin (TN), talin
      2, apolipoprotein E, immunoglobulin lambda light chain (IGL@), immunoglobulin
      kappa variable light chain 1-5 (IGKV1-5), and procollagen C-endopeptidase
      enhancer 1 (PCOLCE). Expression of DBP, SOD1 and talin-2 was validated by western
      blot. Our results may provide better understanding of the pathophysiologic
      mechanisms underlying epileptogenesis and possible epilepsy biomarkers.

PMID- 19109934
TI  - Pax2 in the optic nerve of the goldfish, a model of continuous growth.
AB  - Pax2 is a well known transcription factor which participates in optic nerve
      development. It assures the correct arrival and package of the newly formed
      retinal axons and the adequate differentiation of the newly formed glial cells.
      Pax2 protein expression is continuous throughout adult life in the goldfish optic
      nerve. We have found two populations of astrocytes in the optic nerve: Pax2(+)
      and Pax2(-). Moreover, we have observed that the Pax2(+) astrocytes from the
      optic nerve head present differences in number and organization to those of the
      rest of the optic nerve. In the optic nerve head some Pax2(+) astrocytes,
      principally localized in the glia limitans, have thin GFAP(+) processes and weak
      cytokeratin and ZO1 immunolabeling. Several Pax2(+) astrocytes are in close
      association with the GFAP(+)/GS(+) Muller cell vitreal processes and with the
      growing Zn8(+) retinal ganglion cell axons. However, in the intraorbital segment,
      Pax2(+) astrocytes are more numerous and they have strongly cytokeratin(+)/ZO1(+)
      processes and form part of the reticular astrocytes and the glia limitans. We
      also found Pax2(-) astrocytes in both the optic nerve head and the intraorbital
      segment. In the intraorbital segment there are GS(+)/Pax2(-) cells which are
      absent from the optic nerve head. We propose that the maintenance of Pax2 protein
      expression in adult goldfish optic nerve could be related to the continuous
      addition of new ganglion cell axons and new glial cells.

PMID- 19109933
TI  - Exposure to cerebrospinal fluid of sporadic amyotrophic lateral sclerosis
      patients alters Nav1.6 and Kv1.6 channel expression in rat spinal motor neurons.
AB  - Cerebro Spinal Fluid (CSF) from patients with ALS has been documented to have a
      toxic effect on motor neurons both in vivo and in vitro. Here we show that the
      CSF from Amyotrophic Lateral Sclerosis (ALS) patients (ALS-CSF) has the potential
      to perturb ion channel expression, specifically the Na(v)1.6, and K(v)1.6
      channels in newborn rat spinal motor neurons both in vivo and in vitro. ALS-CSF
      and CSF from nonALS patients (nonALS-CSF) were intrathecally injected into 3-day
      old rat pups at the rate of 1 microl/2.5 min using a microinjector. In addition,
      embryonic rat spinal cord cultures were also exposed to 10% ALS or nonALS-CSF on
      the 9th day in vitro (9DIV) in serum free DMEM medium. After 48 h of CSF
      exposure, the cultures and the spinal cord sections were processed for
      immunostaining of the above mentioned ion channels. We observed a decrease in the
      expression of Na(v)1.6 and K(v)1.6 channels in motor neurons in ALS-CSF treated
      group, and the presence of trophic factors like Brain Derived Neurotrophic Factor
      (BDNF) and Ciliary Neurotrophic Factor CNTF partially reversed the effects
      produced by ALS-CSF. Altered expression of these voltage-gated channels may
      interfere with the electrical activity of motor neurons, and thereby lead to the
      degeneration of neurons.

PMID- 19109935
TI  - Effect of gamma irradiation on the efficacy of beta-glucan against acetaminophen
      induced toxicity in mice.
AB  - The present study was conducted to compare the efficacy of unirradiated beta
      glucan (UBG) and gamma irradiated beta-glucan (GIBG) against acetaminophen (APAP)
      induced hepatotoxicity in mice. Mice of BALB/c strain were pretreated with UBG
      and GIBG (50mg/kg, p.o.) for 7 days and on the 8th day they received an overdose
      of APAP (500 mg/kg, i.p.). Eight hours after the APAP injection, the levels of
      serum aminotransferase (AST) and alanine aminotransferase (ALT) were measured and
      liver, kidney and lung tissue were examined for morphological changes. A
      significant elevation (p<0.001) of the levels of AST and ALT was observed in mice
      toxicated with APAP. Histology data revealed severe liver centrilobular necrosis,
      portal vein damage with apparent toxicity in renal glomerulus and lung
      inflammation associated with edema. However, a significant inhibition (p<0.05) in
      the elevation of AST and ALT was observed in mice that received UBG and GIBG
      compared with APAP-treated mice. Histology examination revealed the non
      statistical difference between the protective effects of GIBG and UBG against
      acetaminophen challenge. In conclusion, it was demonstrated that gamma
      irradiation induced no severe alteration in the protective activity of beta
      glucan against APAP-induced hepatotoxicity.

PMID- 19109936
TI  - Citrullinated fibrinogen shows defects in FPA and FPB release and fibrin
      polymerization catalyzed by thrombin.
AB  - BACKGROUND: Antibody-antigen complexes formed by IgG autoantibodies against
      citrullinated proteins and citrullinated forms of the alpha- and beta-chains of
      fibrin in rheumatoid synovial tissue play a key role in the pathophysiology of
      rheumatoid arthritis. METHODS: Recombinant fibrinogen was citrullinated by rabbit
      skeletal muscle peptidylarginine deiminase so that we could analyze the function
      of citrullinated fibrinogen. Namely, thrombin-catalyzed fibrin polymerization and
      fibrinopeptide release, protection against plasmin digestion, and factor XIIIa
      catalyzed cross-linking of fibrin or fibrinogen were performed. RESULTS: Strong
      citrullination of the Aalpha- and Bbeta-chains and weak citrullination of the
      gamma-chain were detected by an anti-modified citrulline detection kit.
      Citrullinated fibrinogen did not release FPA or FPB by thrombin catalyzation and
      no thrombin-stimulated conversion of fibrinogen into fibrin occurred. The
      citrullination of fibrinogen did not affect the 3 functions of the C-terminal
      gamma-chain, "a-hole," low affinity Ca binding, and gamma-gamma cross-linking.
      CONCLUSION: Our functional analyses demonstrated that no thrombin-stimulated
      conversion of fibrinogen into fibrin occurred, because citrullinated fibrinogen
      did not release FPA or FPB after thrombin catalyzation. Our results and those of
      other reports suggest that citrullinated fibrin and fibrinogen are present in the
      synovium and might both be associated with the pathophysiology of RA.

PMID- 19109937
TI  - Up-regulation of the endoplasmic reticulum stress-response in periodontal
      disease.
AB  - BACKGROUND: Endoplasmic reticulum (ER) stress is the cell response by activation
      of the unfolded protein response (UPR) pathway in a variety of conditions such as
      infection and aging. The UPR may be associated with the pathogenesis of
      periodontal disease because of the induction of apoptosis and activation of
      nuclear factor-kappaB (NF-kappaB), a transcription factor for pro-inflammatory
      cytokines. However, the relationship between ER stress and periodontal disease is
      yet to be determined. METHODS: The expression of UPR-related molecules was
      analyzed by real-time polymerase chain reaction and immunohistochemistry,
      respectively and compared between gingivitis and periodontitis. The gene
      expressions were also analyzed for macrophages stimulated with
      lipopolysaccharides (LPS) from Escherichia coli (E. coli), and Porphyromonas
      gingivalis (P. gingivalis) or IFN-gamma. RESULTS: The expression levels of UPR
      related genes and HSP60 were significantly higher in periodontitis compared with
      gingivitis lesions. However, LPS from P. gingivalis but not E. coli or IFN-gamma
      failed to up-regulate the gene expression in macrophage. CONCLUSIONS: An
      inflammatory response may have profound effect on the UPR response, particularly
      in periodontitis patients. Considering the histological nature of periodontitis
      and the link between UPR and inflammatory responses via NF-kappaB, ER stress in B
      cells could be another pathological mechanism underlying periodontal disease.

PMID- 19109938
TI  - Oxidative stress and delta-ALA-D activity in different conditioning regimens in
      allogeneic bone marrow transplantation patients.
AB  - OBJECTIVES: To compare different conditioning regimens (CR), in order to
      determine whether either of them could be less toxic to allogeneic bone marrow
      transplantation (BMT) patients in terms of oxidative stress and also analyze
      delta-ALA-D activity as a possible marker of oxidative stress. DESIGN AND
      METHODS: Lipid peroxidation, vitamin C, thiol groups levels and catalase,
      superoxide dismutase and delta-ALA-D activity were determined in 21 healthy
      controls, 5 patients with fludarabine+cyclophosphamide (FluCy) CR, 12 with
      busulfan+cyclophosphamide (BuCy) and 4 with cyclophosphamide+total body
      irradiation (CyTBI). RESULTS: There were a decrease in enzymatic and non
      enzymatic antioxidants, in delta-ALA-D activity, and in all CRs and an increase
      in lipid peroxidation more pronounced in CyTBI CR. CONCLUSIONS: All CRs promoted
      oxidative stress in allogeneic BMT patients, but this was more pronounced with
      CyTBI and delta-ALA-D activity seemed to be an additional biomarker of oxidative
      stress in these patients.

PMID- 19109939
TI  - Rapid determination of serum testosterone by liquid chromatography-isotope
      dilution tandem mass spectrometry and a split sample comparison with three
      automated immunoassays.
AB  - OBJECTIVES: To develop a rapid convenient-to-implement high performance liquid
      chromatography-isotope dilution tandem mass spectrometry (LC-IDMS/MS) method for
      determination of serum testosterone concentration in routine clinical
      laboratories. METHODS: Following extraction by organic solvents, an Agilent 1200
      Series HPLC system coupled to an API 5000 mass spectrometer equipped with an
      atmospheric pressure chemical ionization ion source was used to separate, detect
      and quantify serum testosterone. Ion-transitions of m/z 289.2-->109.1 and 294.2-
      >113.2 were used to monitor testosterone and testosterone-2,2,4,6,6-d(5),
      respectively. RESULTS: Functional sensitivity was 0.056 nmol/L (CV 20%). Within
      run and total imprecision were 4.6% and 5.2% at 1.3 nmol/L, 2.4% and 4.3% at 11.0
      nmol/L, and 1.9% and 1.9% at 23.4 nmol/L respectively. The LC-MS/MS method agreed
      closely with three automated immunoassays when the concentration of testosterone
      exceeded 3 nmol/L. However, the immunoassays showed a positive bias at
      concentrations below 3 nmol/L. CONCLUSION: This method provides a rapid, simple,
      highly selective and sensitive procedure that can be easily used for
      determination of serum testosterone in routine clinical laboratories. It measures
      serum testosterone precisely and accurately at concentrations found in children
      and adults of both genders.

PMID- 19109940
TI  - Development of a freeze-drying protocol for the long-term storage of S9-fraction
      at ambient temperatures.
AB  - The purpose of this study was to investigate the long-term stabilization of the
      liver S9-fraction that is widely used in genotoxicity assays in order to mimic
      bio-activating processes of xenobiotics in vitro. A successful long-term
      stabilization of the S9-fraction meets the growing demand for the construction of
      a lab independent device for the detection of genotoxic compounds in field
      studies with an integrated module for the metabolic activation of pre-genotoxic
      compounds. The carbohydrates sucrose, trehalose and raffinose were tested in
      different concentrations or mixtures in order to increase the product stability
      of the S9-fraction during and after freeze-drying. The activity of the freeze
      dried S9-samples was evaluated by means of their potential to activate pre
      genotoxic compounds. The successful long-term stabilization of enzymes of the
      rodent liver S9-fraction for 6 weeks at room temperature by freeze-drying in the
      presence of 250 mM trehalose is presented.

PMID- 19109941
TI  - Increased IP3/Ca2+ signaling compensates depletion of LET-413/DLG-1 in C. elegans
      epithelial junction assembly.
AB  - The let-413/scribble and dlg-1/discs large genes are key regulators of epithelial
      cell polarity in C. elegans and other systems but the mechanism how they organize
      a circumferential junctional belt around the apex of epithelial cells is not well
      understood. We report here that IP(3)/Ca(2+) signaling is involved in the let
      413/dlg-1 pathway for the establishment of epithelial cell polarity during the
      development in C. elegans. Using RNAi to interfere with let-413 and dlg-1 gene
      functions during post-embryogenesis, we discovered a requirement for LET-413 and
      DLG-1 in the polarization of the spermathecal cells. The spermatheca forms an
      accordion-like organ through which eggs must enter to complete the ovulation
      process. LET-413- and DLG-1-depleted animals exhibit failure of ovulation.
      Consistent with this phenotype, the assembly of the apical junction into a
      continuous belt fails and the PAR-3 protein and microfilaments are no longer
      localized asymmetrically. All these defects can be suppressed by mutations in IPP
      5, an inositol polyphosphate 5-phosphatase and in ITR-1, an inositol triphosphate
      receptor, which both are supposed to increase the intracellular Ca(2+) level.
      Analysis of embryogenesis revealed that IP(3)/Ca(2+) signaling is also required
      during junction assembly in embryonic epithelia.

PMID- 19109942
TI  - Administration of angiotensin II, but not catecholamines, induces accumulation of
      lipids in the rat heart.
AB  - Accumulation of lipids in the heart may cause cardiac dysfunction in various
      disorders, such as obesity and diabetes. In the current study, we have
      investigated whether administration of angiotensin II or norepinephrine induces
      accumulation of lipids and/or changes in the expression of genes related to lipid
      metabolism in the rat heart. Lipid deposition was found in myocardial, vascular
      wall, and perivascular cells of the angiotensin II-infused rat heart, and
      superoxide generation was increased in these lipid-positive cells. By contrast,
      intracardiac lipid deposition was not found in the heart of norepinephrine
      induced hypertensive rats. Triglyceride content in the heart tissue of
      angiotensin II-infused rats increased more than 3-fold as compared with untreated
      controls. Losartan completely, but hydralazine only partially, suppressed the
      angiotensin II-induced intracardiac lipid deposition and increase in tissue
      triglyceride content. Administration of angiotensin II upregulated the mRNA
      expression of sterol regulatory element-binding protein-1c and fatty acid
      synthase, but downregulated that of uncoupling protein 2 and 3, in a manner
      dependent on the angiotensin AT(1) receptor. Collectively, these results suggest
      that angiotensin II may be involved in modulating both intracardiac lipid content
      and lipid metabolism-related gene expression, in part via an angiotensin AT(1)
      receptor-dependent and pressor-independent mechanism.

PMID- 19109943
TI  - Influence of gender and sex hormones on 5alpha-dihydrotestosterone elicited
      effect in isolated left atria of rats: Role of beta-adrenoceptors and ornithine
      decarboxylase activity.
AB  - Androgens elicit an acute cardiotonic effect in cardiac preparations of rats.
      This effect is produced via an extracellular interaction that may be coupled to
      pertussis-sensitive G-proteins and is associated with an increase in cAMP,
      polyamine synthesis and intracellular calcium. The nature of the targets and the
      existence of a dimorphic effect in this nongenomic effect of androgens are
      unknown. The purpose of this study was to characterize a possible gender and sex
      hormone influence on the 5alpha-dihydrotestosterone-elicited cardiotonic effect,
      taking into account the possible role of the beta-adrenoceptors and ornithine
      decarboxylase activity on this response. [Float1]Regarding this, the effect of
      5alpha-dihydrotestosterone on isolated left atria from male, estrogenized female
      and gonadectomized male and female rats was studied. The results showed that
      5alpha-dihydrotestosterone-elicited cardiotonic effect was preserved independent
      of gender and sex hormones, being higher in control males than in the rest of the
      groups. This correlated with the testosterone plasma levels, except in
      estrogenized females, suggesting that the androgens positively and the estrogens
      negatively regulated the response. In all groups, 5alpha-dihydrotestosterone
      produced an increase in cAMP levels, but only in control males did it produce an
      increase in ornithine decarboxylase activity. In the other groups, the absence of
      an effect on ornithine decarboxylase might limit the capability of the response
      to the androgen. Altogether, androgens may help to control cardiac performance by
      a direct interaction on the heart in both sexes. Gender and sex differences in
      the magnitude of inotropism being due mainly to changes in beta-adrenoceptors and
      cAMP production and in intracellular polyamine synthesis.

PMID- 19109944
TI  - Co-existence of muscarinic and nicotinic receptors and their functional
      interaction in mouse Beta-TC6 cells.
AB  - Mouse Beta-TC6 insulinoma cells possessing nicotinic receptor [Ohtani, M., Oka,
      T., Badyuk, M., Xiao, Y., Kellar, KJ., Daly, JW., 2006. Mouse beta-TC6 insulinoma
      cells: high expression of functional alpha3beta4 nicotinic receptors mediating
      membrane potential, intracellular calcium, and insulin release. Mol. Pharmacol.
      69, 899-907.] also expressed M(3) and M(4) muscarinic receptors. Carbamylcholine,
      a mixed muscarinic/nicotinic receptor agonist, or oxotremorine M, a selective
      muscarinic agonist, elicited an elevation of cytoplasmic Ca(2+) concentration
      ([Ca(2+)](i)) and release of insulin. The maximal [Ca(2+)](i) response induced by
      carbamylcholine was larger than that of oxotremorine M or that of nicotine,
      suggesting that carbamylcholine enhanced the [Ca(2+)](i) response by stimulating
      two types of receptor. M(3) and M(4) muscarinic receptor antagonists inhibited
      the [Ca(2+)](i) responses to carbamylcholine and oxotremorine M, suggesting the
      involvement of these muscarinic receptors in the regulation of [Ca(2+)](i). In
      addition, pretreatment with carbamylcholine inhibited the [Ca(2+)](i) responses
      to oxotremorine M or nicotine, indicating that the effect of carbamylcholine on
      [Ca(2+)](i) was mediated by both muscarinic and nicotinic receptors. A
      phospholipase C (PLC) inhibitor U73122, a protein kinase C (PKC) inhibitor
      chelerythrine and a phospholipase A(2) (PLA(2)) inhibitor AACOCF(3) inhibited the
      [Ca(2+)](i) response to carbamylcholine or oxotremorine M, while these inhibitors
      did not block the effect of nicotine. Carbamylcholine induced a smaller extent of
      insulin secretion than oxotremorine M, suggesting that concomitant stimulation of
      muscarinic and nicotinic receptors by carbamylcholine resulted in the negative
      type of the receptor interaction.

PMID- 19109945
TI  - Changes in the properties of allosteric and orthosteric GABAB receptor ligands
      after a continuous, desensitizing agonist pretreatment.
AB  - It has been estimated that only 15% of the compounds classified as silent G
      protein-coupled receptor antagonists are indeed devoid of either positive or
      negative intrinsic efficacy. Considering that 40% of all drugs on the market
      target G protein-coupled receptors mainly as orthosteric ligands, elucidating
      their intrinsic properties is becoming increasingly important. While agonism can
      be demonstrated using appropriately sensitive experimental setups, the detection
      of inverse agonism can be limited by a low degree of constitutive activity in
      many assay systems. In this study, changes in ligand behavior upon a lasting
      pretreatment with gamma-aminobutyric acid (GABA), that induced receptor
      desensitization, were observed, measuring the second messenger cyclic AMP (cAMP)
      in a GABA(B) receptor-expressing recombinant cell line. The GABA(B) receptor
      partial agonist 2-OH-saclofen lost its ability to inhibit 7beta-forskolin-induced
      cAMP production upon GABA-pretreatment. The "silent" receptor antagonists
      CGP62349, CGP52432, CGP56999 and SCH50911, on the other hand, stimulated 7beta
      forskolin-induced cAMP production under these conditions. The inverse agonism of
      CGP56999 was inhibited by the efficacy-deficient 2-OH-saclofen, proving it was
      truly mediated through the orthosteric site of the GABA(B) receptor. Finally, the
      positive allosteric modulator GS39783, which previously only marginally inhibited
      cAMP production, suppressed it by 60% both alone and in the presence of the
      competitive receptor antagonist 2-OH-saclofen, thus GS39783 became an allosteric
      receptor agonist at desensitized GABA(B) receptors. These changes likely reflect
      adaptations in the mechanisms of GABA(B) receptor function following
      desensitization and may be important in the elucidation of intrinsic ligand
      efficacies as well as for the consequences of continuous drug treatment.

PMID- 19109946
TI  - Acid increases inflammatory pain in rats: effect of local peripheral ASICs
      inhibitors.
AB  - The purpose of this study was to assess the possible antinociceptive effect of
      the acid sensing ion channels (ASICs) inhibitors amiloride and benzamil after
      local peripheral administration in three models of inflammatory pain in rats.
      Reduction of pH, from 7.4 to 5.8 units, significantly increased the
      flinching/licking behavior induced by either 0.1% serotonin, 0.1% capsaicin or
      0.5% formalin. Local peripheral ipsilateral, but not contralateral, injection of
      amiloride or benzamil significantly reduced nociceptive behaviors (flinching and
      licking/lifting) induced by serotonin, capsaicin or formalin in acidic conditions
      (pH 6.2). Interestingly, benzamil produced antinociception at low doses (0.001
      0.1 microM/paw) while higher doses (1 microM/paw) did not affect capsaicin- or
      formalin-induced licking/lifting. Our data suggest that local peripheral
      inhibition of ASICs play an important role in inflammatory pain.

PMID- 19109947
TI  - Proteome-based epitopic peptide scanning along PSA.
AB  - The specific definition of the immunogenic peptide repertoire from tumor
      associated-antigens (TAAs) is of crucial importance for designing effective
      immunotherapeutical treatments. Multiple mechanisms, at different levels and in
      complementary manners, contribute to the generation of immunogenic peptides.
      Using as an experimental model the prostate specific antigen (PSA) and a murine
      monoclonal antibody (MAb) raised against human PSA, the role of PSA peptide 1)
      similarity to the murine proteome, 2) affinity to H2-Ad/Ed molecules, and 3)
      proteasomal cleavage pattern were investigated. We report that the core of the
      interaction between the anti-PSA MAb ER-PR8 and the prostatic antigen is located
      in the pentapeptide motif PSA(27-31)GGWEC. The pentapeptide motif is
      characterized by having no sequence similarity to the murine proteome and a low
      number of potential proteolytic sites.

PMID- 19109948
TI  - Recruitment of protein phosphatase 2A to dorsal ruffles by platelet-derived
      growth factor in smooth muscle cells: dephosphorylation of Hsp27.
AB  - In this study, we investigated the mechanism underlying Hsp27 dephosphorylation
      in smooth muscle cells. We found that protein phosphatase 2A (PP2A)
      dephosphorylates Hsp27. In addition, Hsp27 dephosphorylation was regulated by
      membrane cholesterol content. We showed that PDGF induced a three-fold increase
      in the proportion of PP2A activity regulated by cholesterol in the Triton
      insoluble fraction of cell lysates. Moreover, cholesterol depletion decreased the
      amount of PP2A recovered in Triton-insoluble fraction. Thus, PDGF might regulate
      a small pool of PP2A associated with lipid rafts. Isolation of detergent
      resistant membrane fragments by Optiprep-gradient density indicated that this
      pool of PP2A was not associated with caveolae, but was recovered in a higher
      density fraction (DRM-H) with ganglioside GM1, alpha-actinin, Hsp27 and p34, a
      component of Arp2/3 complex. These proteins were also present in dorsal ruffles
      containing GM1 but not caveolin-1. Phosphorylated Hsp27 levels detected in dorsal
      ruffles were variable. Cholesterol depletion, which inhibits dorsal ruffle
      formation, decreased PP2A levels and increased the Hsp27-P to Hsp27 ratio in DRM
      H. These findings suggest that Hsp27 is dephosphorylated by PP2A in dorsal
      ruffles, in non-caveolar lipid raft microdomains. However, similarly to p34, non
      phosphorylated Hsp27 is associated to non-raft membrane domains at the leading
      edge of lamellipodia.

PMID- 19109949
TI  - Retinal ganglion cell death and optic nerve degeneration by genetic ablation in
      adult mice.
AB  - Despite the magnitude of the problem, no effective treatments exist to prevent
      retinal ganglion cell (RGC) death and optic nerve degeneration from occurring in
      diseases affecting the human eye. Animal models currently available for
      developing treatment strategies suffer from cumbersome procedures required to
      induce RGC death or rely on mutations that induce defects in developing retinas
      rather than in mature retinas of adults. Our objective was to develop a robust
      genetically engineered adult mouse model for RGC loss and optic nerve
      degeneration based on genetic ablation. To achieve this, we took advantage of
      Pou4f2 (Brn3b), a gene activated immediately as RGCs begin to differentiate and
      expressed throughout life. We generated adult mice whose genomes harbored a
      conditional Pou4f2 allele containing a floxed-lacZ-stop-diphtheria toxin A
      cassette and a CAGG-Cre-ER transgene. In this bigenic model, Cre recombinase is
      fused to a modified estrogen nuclear receptor in which the estrogen-binding
      domain binds preferentially to the estrogen agonist tamoxifen rather than to
      endogenous estradiol. Upon binding to the estrogen-binding domain, tamoxifen
      derepresses Cre recombinase, leading to the efficient genomic deletion of the
      floxed-lacZ-stop DNA sequence and expression of diphtheria toxin A. Tamoxifen
      administered to adult mice at different ages by intraperitoneal injection led to
      rapid RGC loss, reactive gliosis, progressive degradation of the optic nerve over
      a period of several months, and visual impairment. Perhaps more reflective of
      human disease, partial loss of RGCs was achieved by modulating the tamoxifen
      treatment. Especially relevant for RGC death and optic nerve degeneration in
      human retinal pathologies, RGC-ablated retinas maintained their structural
      integrity, and other retinal neurons and their connections in the inner and outer
      plexiform layers appeared unaffected by RGC ablation. These events are hallmarks
      of progressive optic nerve degeneration observed in human retinal pathologies and
      demonstrate the validity of this model for use in developing stem cell therapies
      for replacing dead RGCs with healthy ones.

PMID- 19109950
TI  - Effects of poly(2-hydroxyethyl methacrylate) and poly(vinyl-pyrrolidone) hydrogel
      implants on myopic and normal chick sclera.
AB  - There has been generally little attention paid to the utilization of biomaterials
      as an anti-myopia treatment. The purpose of this study was to investigate whether
      polymeric hydrogels, either implanted or injected adjacent to the outer scleral
      surface, slow ocular elongation. White Leghorn (Gallus gallus domesticus) chicks
      were used at 2 weeks of age. Chicks had either (1) a strip of poly(2-hydroxyethyl
      methacrylate) (pHEMA) implanted monocularly against the outer sclera at the
      posterior pole, or (2) an in situ polymerizing gel [main ingredient: poly(vinyl
      pyrrolidone) (PVP)] injected monocularly at the same location. Some of the eyes
      injected with the polymer were fitted with a diffuser or a -10D lens. In each
      experiment, ocular lengths were measured at regular intervals by high frequency A
      scan ultrasonography, and chicks were sacrificed for histology at staged
      intervals. No in vivo signs of either orbital or ocular inflammation were
      observed. The pHEMA implant significantly increased scleral thickness by the
      third week, and the implant became encapsulated with fibrous tissue. The PVP
      injected eyes left otherwise untreated, showed a significant increase in scleral
      thickness, due to increased chondrocyte proliferation and extracellular matrix
      deposition. However, there was no effect of the PVP injection on ocular
      elongation. In eyes wearing optical devices, there was no effect on either
      scleral thickness or ocular elongation. These results represent "proof of
      principle" that scleral growth can be manipulated without adverse inflammatory
      responses. However, since neither approach slowed ocular elongation, additional
      factors must influence scleral surface area expansion in the avian eye.

PMID- 19109951
TI  - Neural stem/progenitor cells modulate immune responses by suppressing T
      lymphocytes with nitric oxide and prostaglandin E2.
AB  - We and others have reported that neural stem/progenitor cells (NSCs) may exert
      direct anti-inflammatory activity. This action has been attributed, in part, to T
      cell suppression. However, how T-cells become suppressed by NSCs remains
      unresolved. In this study, we explored one of these mechanisms and challenged
      some previously advanced hypotheses regarding underlying NSC-mediated T-cell
      suppression. We employed an easily observable and manipulatable system in which
      activated and non-activated T-cells were co-cultured with a stable well
      characterized clone of lacZ-expressing murine NSCs. As in previous reports, NSCs
      were found to inhibit T-cell proliferation. However, this inhibition by NSCs was
      not due to suppression of T cell activation or induction of apoptosis of T cells
      during the early activation stage. High levels of nitric oxide (NO) and
      prostaglandin E2 (PGE2) were induced in the T cells when co-cultured with NSCs.
      In addition, inducible NOS (iNOS) and microsomal type 1 PGES (mPGES-1) were
      readily detected in NSCs in co-culture with T-cells, but not at all in NSCs
      cultured alone or in activated T cells cultured with or without NSCs. This
      finding suggested that activated T cells induced NO and PGE2 production in the
      NSCs. Furthermore, T-cell proliferation inhibited by co-culture with the NSCs was
      significantly restored by inhibitors of NO and PGE2 production. Therefore, NSCs
      appear to suppress T-cells, at least in part, by NO and PGE2 production which, in
      turn, would account for the well-documented reduction of central nervous system
      immunopathology by transplanted NSCs.

PMID- 19109953
TI  - Plasmodium yoelii: assessment of production and role of nitric oxide during the
      early stages of infection in susceptible and resistant mice.
AB  - There is conflicting evidence regarding the role of nitric oxide (NO) in the
      process of resistance against blood-stage malaria parasites. In this study, we
      used two strains of mice infected with Plasmodium yoelii 17XL in order to assess
      the NO production profile and its possible role during the early stage of malaria
      infection. We found a greater elevation of NO production associated with a sharp
      increase in the levels of IFN-gamma in infected DBA/2 mice, compared with
      infected BALB/c mice. This difference was associated with relatively lower
      parasitemia, a higher constituent ratio of infected reticulocytes, and greater
      survival in DBA/2 mice. Endogenous IFN-gamma driving Th1 immunity was responsible
      for NO production. Moreover, schizonts treated in vitro with NO donors caused a
      delayed infection to BALB/c mice in a dose and time-dependent manner. These data,
      thus, suggest that NO may play an inhibitory role in Plasmodium infection.

PMID- 19109954
TI  - Pulmonary angiogenesis in a rat model of hepatopulmonary syndrome.
AB  - BACKGROUND & AIMS: Hepatopulmonary syndrome (HPS), defined as intrapulmonary
      vasodilation, occurs in 10%-30% of cirrhotics and increases mortality. In a rat
      model of HPS induced by common bile duct ligation (CBDL), but not thioacetamide
      (TAA)-induced nonbiliary cirrhosis, lung capillary density increases, monocytes
      accumulate in the microvasculature, and signaling factors in the angiogenesis
      pathway (Akt and endothelial nitric oxide synthase [eNOS]) are activated.
      Pentoxifylline (PTX) directly decreases lung endothelial Akt and eNOS activation,
      blocks intravascular monocyte accumulation, and improves experimental HPS; we
      evaluated whether pulmonary angiogenesis develops in this model. METHODS: TAA-
      and PTX-treated animals were evaluated following CBDL. Lung angiogenesis was
      assessed by quantifying factor VIII-positive microvessels and levels of von
      Willebrand factor (vWf), vascular endothelial cadherin (VE-cadherin), and
      proliferating cell nuclear antigen (PCNA). Angiogenic factors including phospho
      Akt, phospho-eNOS, vascular endothelial growth factor (VEGF)-A, and phospho-VEGF
      receptor-2 (p-VEGFR-2) were compared and monocyte accumulation was assessed.
      RESULTS: Following CBDL, but not TAA exposure, rats developed HPS that was
      temporally correlated with increased numbers of lung microvessel; increased
      levels of vWf, VE-cadherin and PCNA; and activation of Akt and eNOS. Angiogenesis
      was accompanied by increased pulmonary VEGF-A and p-VEGFR-2 levels, with VEGF-A
      staining in accumulated intravascular monocytes and alveolar endothelial cells.
      Following CBDL, PTX-treated rats had reduced numbers of microvessels, reduced
      lung monocyte accumulation, downregulation of pulmonary angiogenic factors, and
      reduced symptoms of HPS. CONCLUSIONS: A specific increase in pulmonary
      angiogenesis occurs as experimental HPS develops, accompanied by activation of
      VEGF-A-associated angiogenic pathways. PTX decreases the angiogenesis, reduces
      the symptoms of HPS, and downregulates VEGF-A mediated pathways.

PMID- 19109960
TI  - Sequential therapy for Helicobacter pylori: a two for one deal that's worth the
      extra effort?

PMID- 19109959
TI  - Roles of infection, inflammation, and the immune system in cholesterol gallstone
      formation.
AB  - Cholesterol gallstone formation is a complex process mediated by genetic and
      environmental factors. Until recently, the role of the immune system in the
      pathogenesis of cholesterol gallstones was not considered a valid topic of
      research interest. This review collates and interprets an extensive body of basic
      literature, some of which is not customarily considered to be related to
      cholelithogenesis, describing the multiple facets of the immune system that
      appear to be involved in cholesterol cholelithogenesis. A thorough understanding
      of the immune interactions with biliary lipids and cholecystocytes should modify
      current views of the pathogenesis of cholesterol gallstones, promote further
      research on the pathways involved, and lead to novel diagnostic tools,
      treatments, and preventive measures.

PMID- 19109961
TI  - TWEAK/Fn14 pathway: a nonredundant role in intestinal damage in mice through a
      TWEAK/intestinal epithelial cell axis.
AB  - BACKGROUND AND AIMS: Tumor necrosis factor (TNF) superfamily members have
      attracted attention as new therapeutic targets for treating inflammatory disease.
      TNF-like weak inducer of apoptosis (TWEAK) is a unique, multifunctional TNF
      family cytokine that signals through its receptor, fibroblast growth factor
      inducible molecule 14 (Fn14). The role of this pathway in the intestine has not
      been previously reported. METHODS: The 2,4,6-trinitrobenzene sulfonic acid (TNBS)
      induced colitis model was conducted in TWEAK- or Fn14-deficient mice or in normal
      mice treated with a TWEAK-blocking monoclonal antibody, and clinical severity,
      histopathology, immunohistochemistry for cell infiltrates, TWEAK and Fn14, gene
      expression profiling in the colon, and systemic adaptive immunity were assessed.
      The effect of TWEAK on colon epithelial cell production of inflammatory mediators
      was analyzed in vitro. The gamma-irradiation injury model was conducted in TWEAK-
      or Fn14-deficient mice, and crypt epithelial death was assessed. RESULTS: Colitis
      severity and histologic scores were significantly reduced by TWEAK pathway
      deficiency or TWEAK-blocking monoclonal antibody. Neutrophil and macrophage
      infiltrates, chemokines, cytokines, and matrix metalloproteinase expression were
      reduced in the TWEAK-deficient colon after TNBS administration; however, systemic
      adaptive immune responses to trinitrophenyl were not altered. Fn14 is expressed
      on colon epithelial cells in TNBS colitis, and TWEAK induces epithelial
      production of pathogenic mediators. TWEAK also regulates intestinal epithelial
      turnover, as evidenced by reduced epithelial cell death after gamma-irradiation
      injury in TWEAK and Fn14 knockout mice. CONCLUSIONS: Our studies elucidate a
      nonredundant TWEAK-intestinal epithelial cell axis and suggest that blocking
      TWEAK may dampen chronic intestinal inflammation and allow normal epithelial
      repair.

PMID- 19109962
TI  - Infliximab prevents Crohn's disease recurrence after ileal resection.
AB  - BACKGROUND & AIMS: Crohn's disease commonly recurs after intestinal resection. We
      evaluated whether the administration of infliximab after resective intestinal
      surgery for Crohn's disease reduces postoperative recurrence. METHODS: We
      randomly assigned 24 patients with Crohn's disease who had undergone ileocolonic
      resection to receive intravenous infliximab (5 mg/kg), administered within 4
      weeks of surgery and continued for 1 year, or placebo. The primary end point was
      the proportion of patients with endoscopic recurrence at 1 year. Secondary end
      points were clinical recurrence and remission and histologic recurrence. RESULTS:
      The rate of endoscopic recurrence at 1 year was significantly lower in the
      infliximab group (1 of 11 patients; 9.1%) compared with the placebo group (11 of
      13 patients; 84.6%) (P = .0006). There was a nonsignificant higher proportion of
      patients in clinical remission in the infliximab group (8 of 10; 80.0%) compared
      with the placebo group (7 of 13; 53.8%) (P = .38). The histologic recurrence rate
      at 1 year was significantly lower in the infliximab group (3 of 11 patients;
      27.3%) compared with the placebo group (11 of 13 patients; 84.6%) (P = .01). The
      occurrence of adverse events was similar between the placebo and infliximab
      groups, and none occurred in the immediate postoperative period. CONCLUSIONS:
      Administration of infliximab after intestinal resective surgery was effective at
      preventing endoscopic and histologic recurrence of Crohn's disease.

PMID- 19109963
TI  - Hepatitis B: a "GLOBAL" health challenge.

PMID- 19109965
TI  - Use of diaminofluoresceins to detect and measure nitric oxide in low level
      generating human immune cells.
AB  - Nitric oxide ((*)NO) has been implicated in multiple physiological and
      pathological immune processes. Different methods have been developed to detect
      and quantify (*)NO, where one of the principal difficulties are the accurately
      detection in cellular system with low levels of (*)NO production. The choice of
      the (*)NO detection method to be used depends on the characteristics of the
      experimental system and the levels of (*)NO production which depend on either the
      organism source of samples or the experimental conditions. Recently, high
      sensitive methods to detect and image (*)NO have been reported using 4,5
      diaminofluorescein-based fluorescent probes (DAF) and its derivate 4,5
      diaminofluorescein diacetate (DAF-2 DA). This work was aimed to adapt and
      optimize the use of DAF probes to detect and quantify the (*)NO production in
      systems of high, moderate and low out-put production, especially in human PBMC
      and their subpopulations. Here, we report an original experimental design which
      is useful to detect and estimate (*)NO fluxes in human PBMC and their
      subpopulations with high specificity and sensitivity.

PMID- 19109964
TI  - RNA editing and mitochondrial activity in promastigotes and amastigotes of
      Leishmania donovani.
AB  - Kinetoplast maxicircle DNA sequence organisation was investigated in Leishmania
      donovani, strain 1S LdBob. Gene arrangement in the coding (conserved) region of
      the maxicircle is collinear with that of most trypanosomatids, with individual
      genes showing 80-90% nucleotide identity to Leishmania tarentolae, strain UC. The
      notable exception was an integration of a full-size minicircle sequence in the
      ND1 gene coding region found in L. donovani. Editing patterns of the
      mitochondrial mRNAs investigated also followed L. tarentolae UC patterns,
      including productive editing of the components of respiratory complexes III-V,
      and ribosomal protein S12 (RPS12), as well as the lack of productive editing in
      five out of six pan-edited cryptogenes (ND3, ND8, ND9, G3, G4) found in these
      species. Several guide RNAs for the editing events were localised in minicircles
      and maxicircles in the locations that are conserved between the species.
      Mitochondrial activity, including rates of oxygen consumption, the presence and
      the levels of respiratory complexes and their individual subunits and the steady
      state levels of several mitochondrial-encoded mRNAs were essentially the same in
      axenically grown amastigotes and in promastigotes of L. donovani. However, some
      modulation of mitochondrial activity between these developmental stages was
      suggested by the finding of an amastigote-specific component in complex IV, a
      down-regulation of mitochondrial RNA-binding proteins (MRP) and MRP-associated
      protein (MRP-AP) in amastigotes, and by variations in the levels of RPS12, ND3,
      ND9, G3 and G4 pre-edited transcripts.

PMID- 19109966
TI  - Development of monoclonal antibodies for detection of Antisecretory Factor
      activity in human plasma.
AB  - Antisecretory Factor (AF) is expressed in most tissues and can be demonstrated in
      plasma and other body fluids. Most of the AF in plasma is in an inactive form and
      activation of AF occurs after exposure to bacterial toxins or after intake of
      various dietary components. Patients with chronic diseases involving disturbances
      in inflammatory and secretory processes may benefit from an AF-inducing diet. The
      aim of the present study was to develop an in vitro assay for the analysis of AF
      activity in human plasma. Monoclonal antibodies were raised against a native form
      of AF prepared from human placenta. Nine clones of the monoclonal antibodies
      recognizing AF and AF peptides were identified. With the aid of these antibodies,
      we developed a sensitive ELISA method for direct detection of AF-activity in
      human plasma. The AF activity in plasma from five healthy volunteers was low,
      0.112+/-0.022 (absorbance at 405 nm), before intake of the AF-inducing diet with
      the SPC-Flakes, and increased significantly (p<0.05) to 0.444+/-0.068 after >or=6
      weeks on the diet. A comparison of the plasma-AF values, obtained by the bioassay
      and the immunogenic assay (indirect ELISA), shows that there is a significant
      correlation (r=0.85) between the values from the two methods. The results
      indicate that the ELISA measures AF-activity and has the potential to be an
      important tool for the analysis of AF-activity in further clinical studies on AF
      therapy.

PMID- 19109967
TI  - Matrigel cytometry: a novel method for quantifying angiogenesis in vivo.
AB  - Many of the current in vivo methods to evaluate angiogenesis are poorly
      quantifiable. Recently, the Matrigel plug assay has become the method of choice
      in many studies involving in vivo testing for angiogenesis. When known angiogenic
      factors are mixed with Matrigel and injected subcutaneously into mice,
      endothelial cells migrate into the gel plug. These endothelial cells form vessel
      like structures, a process that mimics the formation of capillary networks. Here,
      we present a modification of the traditional Matrigel assay with improved method
      to quantify the amount of endothelial cells that incorporate into the plug. The
      removed plugs were subjected to a mild protease treatment, yielding intact cells.
      The liberated cells were then stained using an endothelial cell-specific markers,
      and counted by flow cytometry. This novel combination of FACS analysis with the
      traditional Matrigel assay improves the ability to quantify in vivo angiogenesis,
      and for the first time enables to determine the number of migrating and
      proliferating endothelial cells which reflects the angiogenesis rate.

PMID- 19109968
TI  - Enhancement of anamnestic immunospecific antibody response in orally immunized
      chickens.
AB  - Production of immunospecific egg yolk antibodies (IgY antibodies) in egg laying
      hens through oral immunization is an attractive alternative to conventional
      antibody production in mammals for economic reasons as well as for animal welfare
      reasons. Oral immunization results in a systemic humoral response, but oral
      booster immunizations lack efficiency. The aim of the present study was to
      develop immunization schemes in which the concentration of immunospecific IgY
      would increase following oral booster immunizations. Two groups of egg laying
      hens (5 in each group) were immunized orally (each immunization event consisted
      of dosing on three consecutive days) with Bovine Serum Albumin (BSA) in
      combination with RhinoVax (RV) using different immunization schemes. A 3rd group
      served as a reference and received BSA emulsified in Freund's Incomplete Adjuvant
      (FIA) by subcutaneous injection three times and one oral dose with BSA+RV. The
      eggs of the chickens in this group had a significantly higher immunospecific anti
      BSA IgY-concentration than did any of the eggs from the orally immunized
      chickens. One of the immunization regimes (immunizations in weeks 1, 7 and 18)
      clearly included a booster effect of the immunization in week 18, demonstrating
      the presence of memory cells following the two initial oral immunizations.
      Considering that oral immunization results in approximately ten times lower
      concentrations of immunospecific antibodies in the egg yolk, compared to
      traditional subcutaneous immunization schemes, the oral immunization routines
      have to be further refined to compete with parenteral immunization protocols.

PMID- 19109970
TI  - The Helicobacter pylori CagD (HP0545, Cag24) protein is essential for CagA
      translocation and maximal induction of interleukin-8 secretion.
AB  - Pathogenic strains of Helicobacter pylori use a type IV secretion system (T4SS)
      to deliver the toxin CagA into human host cells. The T4SS, along with the toxin
      itself, is coded into a genomic insert, which is termed the cag pathogenicity
      island. The cag pathogenicity island contains about 30 open-reading frames, for
      most of which the exact function is not well characterized or totally unknown. We
      have determined the crystal structure of one of the proteins coded by the cag
      genes, CagD, in two crystal forms. We show that the protein is a covalent dimer
      in which each monomer folds as a single domain that is composed of five beta
      strands and three alpha-helices. Our data show that in addition to a cytosolic
      pool, CagD partially associates with the inner membrane, where it may be exposed
      to the periplasmic space. Furthermore, CagA tyrosine phosphorylation and
      interleukin-8 assays identified CagD as a crucial component of the T4SS that is
      involved in CagA translocation into host epithelial cells; however, it does not
      seem absolutely necessary for pilus assembly. We have also identified significant
      amounts of CagD in culture supernatants, which are not a result of general
      bacterial lysis. Since this localization was independent of the various tested
      cag mutants, our findings may indicate that CagD is released into the supernatant
      during host cell infection and then binds to the host cell surface or is
      incorporated in the pilus structure. Overall, our results suggest that CagD may
      serve as a unique multifunctional component of the T4SS that may be involved in
      CagA secretion at the inner membrane and may localize outside the bacteria to
      promote additional effects on the host cell.

PMID- 19109969
TI  - Secreted frizzled related protein 2 protects cells from apoptosis by blocking the
      effect of canonical Wnt3a.
AB  - We have demonstrated that mesenchymal stem cells overexpressing the survival gene
      Akt can confer paracrine protection to ischemic myocytes both in vivo and in
      vitro through the release of secreted frizzled related protein 2 (Sfrp2).
      However, the mechanisms mediating these effects of Sfrp2 have not been fully
      elucidated. In this study, we studied rat cardiomyoblasts subjected to hypoxia
      reoxygenation (HR) injury to test the hypothesis that Sfrp2 exerts anti-apoptotic
      effect by antagonizing pro-apoptotic properties of specific Wnt ligands. We
      examined the effect of Wnt3a and Sfrp2 on HR-induced apoptosis. Wnt3a
      significantly increased cellular caspase activities and TUNEL staining in
      response to HR. Sfrp2 attenuated significantly Wnt3a-induced caspase activities
      in a concentration dependent fashion. Using a solid phase binding assay, our data
      demonstrates that Sfrp2 physically binds to Wnt3a. In addition, we observed that
      Sfrp2 dramatically inhibits the beta-catenin/TCF transcriptional activities
      induced by Wnt3a. Impressively, Dickkopf-1, a protein that binds to the Wnt
      coreceptor LRP, significantly inhibited the Wnt3a-activated caspase and
      transcriptional activities. Similarly, siRNA against beta-catenin markedly
      inhibited the Wnt3a-activated caspase activities. Consistent with this,
      significantly fewer TUNEL positive cells were observed in siRNA transfected cells
      than in control cells. Together, our data provide strong evidence to support the
      notion that Wnt3a is a canonical Wnt with pro-apoptotic action whose cellular
      activity is prevented by Sfrp2 through, at least in part, the direct binding of
      these molecules. These results can explain the in vivo protective effect of Sfrp2
      and highlight its therapeutic potential for the ischemic heart.

PMID- 19109971
TI  - Terminal adenosyl transferase activity of posttranscriptional regulator HuR
      revealed by confocal on-bead screening.
AB  - Posttranscriptional regulation and RNA metabolism have become central topics in
      the understanding of mammalian gene expression and cell signalling, with the 3'
      untranslated region emerging as the coordinating unit. The 3' untranslated region
      trans-acting factor Hu protein R (HuR) forms a central posttranscriptional
      pathway node bridging between AU-rich element-mediated processes and microRNA
      regulation. While (m)RNA control by HuR has been extensively characterized, the
      molecular mode of action still remains elusive. Here we describe the
      identification of the first RRM3 (RNA recognition motif 3) targeted low molecular
      weight HuR inhibitors from a one-bead-one-compound library screen using confocal
      nanoscanning. A further compound characterization revealed the presence of an ATP
      binding pocket within HuR RRM3, associated with enzymatic activity. Centered
      around a metal-ion-coordinating DxD motif, the catalytic site mediates 3'
      terminal adenosyl modification of non-polyadenylated RNA substrates by HuR. These
      findings suggest that HuR actively contributes to RNA modification and maturation
      and thereby shed an entirely new light on the role of HuR in RNA metabolism.

PMID- 19109972
TI  - Structure-function relationships in fungal large-subunit catalases.
AB  - Neurospora crassa has two large-subunit catalases, CAT-1 and CAT-3. CAT-1 is
      associated with non-growing cells and accumulates particularly in asexual spores;
      CAT-3 is associated with growing cells and is induced under different stress
      conditions. It is our interest to elucidate the structure-function relationships
      in large-subunit catalases. Here we have determined the CAT-3 crystal structure
      and compared it with the previously determined CAT-1 structure. Similar to CAT-1,
      CAT-3 hydrogen peroxide (H(2)O(2)) saturation kinetics exhibited two components,
      consistent with the existence of two active sites: one saturated in the
      millimolar range and the other in the molar range. In the CAT-1 structure, we
      found three interesting features related to its unusual kinetics: (a) a
      constriction in the channel that conveys H(2)O(2) to the active site; (b) a
      covalent bond between the tyrosine, which forms the fifth coordination bound to
      the iron of the heme, and a vicinal cysteine; (c) oxidation of the pyrrole ring
      III to form a cis-hydroxyl group in C5 and a cis-gamma-spirolactone in C6. The
      site of heme oxidation marks the starts of the central channel that communicates
      to the central cavity and the shortest way products can exit the active site. CAT
      3 has a similar constriction in its major channel, which could function as a
      gating system regulated by the H(2)O(2) concentration before the gate. CAT-3
      functional tyrosine is not covalently bonded, but has instead the electron relay
      mechanism described for the human catalase to divert electrons from it. Pyrrole
      ring III in CAT-3 is not oxidized as it is in other large-subunit catalases whose
      structure has been determined. Different in CAT-3 from these enzymes is an
      occupied central cavity. Results presented here indicate that CAT-3 and CAT-1
      enzymes represent a functional group of catalases with distinctive structural
      characteristics that determine similar kinetics.

PMID- 19109973
TI  - HisE11 and HisF8 provide bis-histidyl heme hexa-coordination in the globin domain
      of Geobacter sulfurreducens globin-coupled sensor.
AB  - Among heme-based sensors, recent phylogenomic and sequence analyses have
      identified 34 globin coupled sensors (GCS), to which an aerotactic or gene
      regulating function has been tentatively ascribed. Here, the structural and
      biochemical characterization of the globin domain of the GCS from Geobacter
      sulfurreducens (GsGCS(162)) is reported. A combination of X-ray crystallography
      (crystal structure at 1.5 A resolution), UV-vis and resonance Raman spectroscopy
      reveals the ferric GsGCS(162) as an example of bis-histidyl hexa-coordinated GCS.
      In contrast to the known hexa-coordinated globins, the distal heme-coordination
      in ferric GsGCS(162) is provided by a His residue unexpectedly located at the E11
      topological site. Furthermore, UV-vis and resonance Raman spectroscopy indicated
      that ferrous deoxygenated GsGCS(162) is a penta-/hexa-coordinated mixture, and
      the heme hexa-to-penta-coordination transition does not represent a rate-limiting
      step for carbonylation kinetics. Lastly, electron paramagnetic resonance
      indicates that ferrous nitrosylated GsGCS(162) is a penta-coordinated species,
      where the proximal HisF8-Fe bond is severed.

PMID- 19109974
TI  - DNA replication arrest in response to genotoxic stress provokes early activation
      of stress-activated protein kinases (SAPK/JNK).
AB  - The impact of DNA damage-induced replication blockage for early activation of
      stress kinases [stress-activated protein kinase (SAPK)/c-Jun N-terminal kinase
      (JNK)] is largely unknown. Here, we show that induction of dual phosphorylation
      of SAPK/JNK by the DNA polymerase inhibitor aphidicolin was not ameliorated by
      additional exposure to ultraviolet (UV) light, indicating that overlapping
      mechanisms participate in signaling to SAPK/JNK triggered by both agents. UV
      induced DNA replication blockage, cyclobutane pyrimidine dimer formation and DNA
      strand break induction coincided with SAPK/JNK phosphorylation at early (< or =30
      min) but not late (> or =2 h) time points after exposure. Genotoxin-stimulated
      SAPK/JNK activation was attenuated in nonproliferating cells, indicating that S
      phase-dependent mechanisms are involved in signaling to SAPK/JNK.
      Correspondingly, UV-induced phosphorylation of SAPK/JNK was higher in S-phase
      cells as compared with G(1)-phase cells. Activation of SAPK/JNK by genotoxins was
      below detection limit in nonproliferating human peripheral blood lymphocytes,
      whereas peripheral blood lymphocytes stimulated to proliferation displayed clear
      SAPK/JNK activation. UV-induced phosphorylation of SAPK/JNK was attenuated in XPC
      defective cells, ameliorated in BRCA2 mutated cells and not changed in cells
      lacking ATM, DNA-PK, CSB, XPA, p53, ERCC1 or PARP as compared with the
      corresponding wild types. Based on these data, we suggest that DNA replication
      blockage caused by genotoxin-induced DNA damage contributes to early activation
      of SAPK/JNK.

PMID- 19109975
TI  - The collagen binding domain of gelatinase A modulates degradation of collagen IV
      by gelatinase B.
AB  - Type IV collagen remodeling plays a critical role in inflammatory responses,
      angiogenesis and metastasis. Its remodeling is executed by a family of matrix
      metalloproteinases (MMPs), of which the constitutive gelatinase A (MMP2) and the
      inducible gelatinase B (MMP9) are key examples. Thus, in many pathological
      conditions, both gelatinases act together. Kinetic data are reported for the
      enzymatic processing at 37 degrees C of type IV collagen from human placenta by
      MMP9 and its modulation by the fibronectin-like collagen binding domain (CBD) of
      MMP2. The alpha1 and alpha2 chain components of type IV collagen were cleaved by
      gelatinases and identified by mass spectrometry as well as Edman sequencing.
      Surface plasmon resonance interaction assays showed that CBD bound type IV
      collagen at two topologically distinct sites. On the basis of linked-function
      analysis, we demonstrated that CBD of MMP2 tuned the cleavage of collagen IV by
      MMP9, presumably by inducing a ligand-linked structural change on the type IV
      collagen. At low concentrations, the CBD bound the first site and thereby
      allosterically modulated the binding of MMP9 to collagen IV, thus enhancing the
      collagenolytic activity of MMP9. At high concentrations, CBD binding to the
      second site interfered with MMP9 binding to collagen IV, acting as a competitive
      inhibitor. Interestingly, modulation of collagen IV degradation by inactive forms
      of MMP2 also occurred in a cell-based system, revealing that this
      interrelationship affected neutrophil migration across a collagen IV membrane.
      The regulation of the proteolytic processing by a catalytically inactive domain
      (i.e., CBD) suggests that the two gelatinases might cooperate in degrading
      substrates even when either one is inactive. This observation reinforces the idea
      of exosite targets for MMP inhibitors, which should include all macromolecular
      substrate recognition sites.

PMID- 19109977
TI  - The supramolecular organization of the C. elegans nuclear lamin filament.
AB  - Nuclear lamins are involved in most nuclear activities and are essential for
      retaining the mechano-elastic properties of the nucleus. They are nuclear
      intermediate filament (IF) proteins forming a distinct meshwork-like layer
      adhering to the inner nuclear membrane, called the nuclear lamina. Here, we
      present for the first time, the three-dimensional supramolecular organization of
      lamin 10 nm filaments and paracrystalline fibres. We show that Caenorhabditis
      elegans nuclear lamin forms 10 nm IF-like filaments, which are distinct from
      their cytoplasmic counterparts. The IF-like lamin filaments are composed of three
      and four tetrameric protofilaments, each of which contains two partially
      staggered anti-parallel head-to-tail polymers. The beaded appearance of the lamin
      filaments stems from paired globular tail domains, which are spaced regularly,
      alternating between 21 nm and 27 nm. A mutation in an evolutionarily conserved
      residue that causes Hutchison-Gilford progeria syndrome in humans alters the
      supramolecular structure of the lamin filaments. On the basis of our structural
      analysis, we propose an assembly pathway that yields the observed 10 nm IF-like
      lamin filaments and paracrystalline fibres. These results serve also as a
      platform for understanding the effect of laminopathic mutations on lamin
      supramolecular organization.

PMID- 19109976
TI  - Design and signaling mechanism of light-regulated histidine kinases.
AB  - Signal transduction proteins are organized into sensor (input) domains that
      perceive a signal and, in response, regulate the biological activity of effector
      (output) domains. We reprogrammed the input signal specificity of a normally
      oxygen-sensitive, light-inert histidine kinase by replacing its chemosensor
      domain by a light-oxygen-voltage photosensor domain. Illumination of the
      resultant fusion kinase YF1 reduced net kinase activity by approximately 1000
      fold in vitro. YF1 also controls gene expression in a light-dependent manner in
      vivo. Signals are transmitted from the light-oxygen-voltage sensor domain to the
      histidine kinase domain via a 40 degrees -60 degrees rotational movement within
      an alpha-helical coiled-coil linker; light is acting as a rotary switch. These
      signaling principles are broadly applicable to domains linked by alpha-helices
      and to chemo- and photosensors. Conserved sequence motifs guide the rational
      design of light-regulated variants of histidine kinases and other proteins.

PMID- 19109978
TI  - Bacterial genome partitioning: N-terminal domain of IncC protein encoded by broad
      host-range plasmid RK2 modulates oligomerisation and DNA binding.
AB  - ParA Walker ATPases form part of the machinery that promotes better-than-random
      segregation of bacterial genomes. ParA proteins normally occur in one of two
      forms, differing by their N-terminal domain (NTD) of approximately 100 aa, which
      is generally associated with site-specific DNA binding. Unusually, and for as yet
      unknown reasons, parA (incC) of IncP-1 plasmids is translated from alternative
      start codons producing two forms, IncC1 (364 aa) and IncC2 (259 aa), whose ratio
      varies between hosts. IncC2 could be detected as an oligomeric form containing
      dimers, tetramers and octamers, but the N-terminal extension present in IncC1
      favours nucleotide-stimulated dimerisation as well as high-affinity and ATP
      dependent non-specific DNA binding. The IncC1 NTD does not dimerise or bind DNA
      alone, but it does bind IncC2 in the presence of nucleotides. Mixing IncC1 and
      IncC2 improved polymerisation and DNA binding. Thus, the NTD may modulate the
      polymerisation interface, facilitating polymerisation/depolymerisation and DNA
      binding, to promote the cycle that drives partitioning.

PMID- 19109980
TI  - Computational models of heart pumping efficiencies based on contraction waves in
      spiral elastic bands.
AB  - We present a framework for modeling biological pumping organs based on coupled
      spiral elastic band geometries and active wave-propagating excitation mechanisms.
      Two pumping mechanisms are considered in detail by way of example: one of a
      simple tube, which represents a embryonic fish heart and another more complicated
      structure with the potential to model the adult human heart. Through finite
      element modeling different elastic contractions are induced in the band. For each
      version the pumping efficiency is measured and the dynamics are evaluated. We
      show that by combining helical shapes of muscle bands with a contraction wave it
      is possible not only to achieve efficient pumping, but also to create desired
      dynamics of the structure. As a result we match the function of the model pumps
      and their dynamics to physiological observations.

PMID- 19109979
TI  - A continuum receptor model of hepatic lipoprotein metabolism.
AB  - A mathematical model describing the uptake of low density lipoprotein (LDL) and
      very low density lipoprotein (VLDL) particles by a single hepatocyte cell is
      formulated and solved. The model includes a description of the dynamic change in
      receptor density on the surface of the cell due to the binding and dissociation
      of the lipoprotein particles, the subsequent internalisation of bound particles,
      receptors and unbound receptors, the recycling of receptors to the cell surface,
      cholesterol dependent de novo receptor formation by the cell and the effect that
      particle uptake has on the cell's overall cholesterol content. The effect that
      blocking access to LDL receptors by VLDL, or internalisation of VLDL particles
      containing different amounts of apolipoprotein E (we will refer to these
      particles as VLDL-2 and VLDL-3) has on LDL uptake is explored. By comparison with
      experimental data we find that measures of cell cholesterol content are important
      in differentiating between the mechanisms by which VLDL is thought to inhibit LDL
      uptake. We extend our work to show that in the presence of both types of VLDL
      particle (VLDL-2 and VLDL-3), measuring relative LDL uptake does not allow
      differentiation between the results of blocking and internalisation of each VLDL
      particle to be made. Instead by considering the intracellular cholesterol content
      it is found that internalisation of VLDL-2 and VLDL-3 leads to the highest
      intracellular cholesterol concentration. A sensitivity analysis of the model
      reveals that binding, unbinding and internalisation rates, the fraction of
      receptors recycled and the rate at which the cholesterol dependent free receptors
      are created by the cell have important implications for the overall uptake
      dynamics of either VLDL or LDL particles and subsequent intracellular cholesterol
      concentration.

PMID- 19109981
TI  - Daidzein administration in vivo reduces myocardial injury in a rat
      ischemia/reperfusion model by inhibiting NF-kappaB activation.
AB  - AIMS: We tested the hypothesis that daidzein may reduce myocardial damage by both
      inhibiting the release of cytokines and limiting the nuclear translocation of NF
      kappaB. MAIN METHODS: Male Sprague-Dawley rats were anesthetized, and the left
      anterior descending coronary artery (LAD) was ligated for 25 min. Twenty-four
      hours after reperfusion was established, the hemodynamics and infarct size were
      examined. KEY FINDINGS: Treatment with daidzein (10 mg/kg, i.p.) 1 h prior to the
      ischemia/reperfusion procedure (I/R) reduced the infarct size by 52.8% (P<0.05).
      Daidzein also significantly improved I/R-induced myocardial contractile
      dysfunction by improving the left ventricular diastolic pressure and the positive
      and negative maximal values of the first derivative of the left ventricular
      pressure. In addition, daidzein reduced the plasma levels of TNF-alpha and IL-6
      in I/R rats and decreased malondialdehyde levels, myeloperoxidase activity,
      catalase activity and neutrophil infiltration in I/R rat myocardium.
      Interestingly, daidzein inhibited I/R-induced myocardial apoptosis by decreasing
      DNA strand breaks and cleaved caspase-3 activity. Furthermore, daidzein inhibited
      both the nuclear translocation of NF-kappaB in I/R rat hearts and the H(2)O(2)
      induced activation of NF-kappaB-luciferase activity in human umbilical vein
      endothelial cells. SIGNIFICANCE: This study reveals that the administration of
      daidzein in vivo attenuates I/R-induced myocardial damage via inhibition of NF
      kappaB activation, which in turn may suppress inflammatory cytokine expression.

PMID- 19109982
TI  - Role of intrinsically disordered protein regions/domains in transcriptional
      regulation.
AB  - In recent years, it has become quite evident that numerous proteins exist as an
      ensemble of conformers that collectively appears to be intrinsically disordered
      (ID). Of particular significance is the growing body of evidence that intrinsic
      disorder is found in disproportionately higher amounts in cell signaling proteins
      and transcription factors, suggesting an important role in their regulatory
      capacity. Since these proteins are known to possess specific regions/domains that
      interact with specific coregulatory proteins for their efficient functioning, the
      large flexible regions in this class of proteins may have an advantage over fully
      folded proteins that can allow them to make more efficient physical functional
      interactions with their target partners, which may represent a mechanism for
      regulation of cellular processes. In fact, recent studies from several
      laboratories have reported existence of ID sequences in such regions in signaling
      proteins that play a critical role in regulating their functions. There are
      reports showing that ID regions/domains commonly exist within proteins with
      modular structures such as transcription factors, and are often located in their
      transactivation domain. Therefore, it is important to find out their existence
      and functional roles in transcriptional regulations by transcription factors. In
      recent years there has been growing evidence suggesting that an induced fit
      process leads to imposition of folded functional structure in these ID protein
      regions/domains. In most cases such binding and folding events have been found to
      occur when ID region encounters its specific binding partner(s).

PMID- 19109983
TI  - Capillary endothelial but not lymphatic function is restored under rosiglitazone
      in Zucker diabetic fatty rats.
AB  - If thiazolidinediones have shown beneficial effects on macrovascular endothelial
      function, their effects on microcirculation and lymphatic function are not well
      documented. The aim of the study was to assess the effect of rosiglitazone on
      interstitial albumin retention and lymphatic function in Zucker Diabetic Fatty
      (ZDF) rats. Three series of 9-14 rats were studied: Lean (fa/?) controls, ZDF
      (Gmi-fa/fa) rats and ZDF rats treated with rosiglitazone from 8 to 26 weeks of
      age (ZDF-ROSI). Albumin retention and lymphatic uptake of interstitial albumin
      (LF/HF ratio) were evaluated on hindquarters with a noninvasive isotopic test
      using technetium-labelled albumin. Vascular Endothelial Growth Factor (VEGF) was
      measured. At week 25, albumin retention was markedly higher in ZDF rats (9.9+/
      1.0%) than in control rats (1.0+/-0.8%, p<0.001), but did not differ
      significantly between the ZDF-ROSI group (2.5+/-1.5%) and the control group.
      LF/HF ratio was similarly increased in the ZDF group (1.14+/-0.07%) and the ZDF
      ROSI group (1.07+/-0.04%) as compared to control rats (0.65+/-0.04%; p<0.001 for
      both). We can deduce that the prevention of the increase of albumin retention
      under rosiglitazone results from a decrease in the capillary filtration of
      albumin. VEGF levels were 7.1+/-1.5, 7.3+/-1.9, 3.5+/-1.6 pg/mL in the control,
      ZDF and ZDF-ROSI groups, respectively (p=0.23). In ZDF rats, rosiglitazone
      prevents interstitial albumin retention and the increase in capillary filtration
      of albumin. However lymphatic function is still impaired and might contribute to
      oedema.

PMID- 19109984
TI  - Dynamic switching between semantic and episodic memory systems.
AB  - It has been suggested that episodic and semantic long-term memory systems
      interact during retrieval. Here we examined the flexibility of memory retrieval
      in an associative task taxing memories of different strength, assumed to
      differentially engage episodic and semantic memory. Healthy volunteers were pre
      trained on a set of 36 face-name pairs over a 6-week period. Another set of 36
      items was shown only once during the same time period. About 3 months after the
      training period all items were presented in a randomly intermixed order in an
      event-related fMRI study of face-name memory. Once presented items differentially
      activated anterior cingulate cortex and a right prefrontal region that previously
      have been associated with episodic retrieval mode. High-familiar items were
      associated with stronger activation of posterior cortices and a left frontal
      region. These findings fit a model of memory retrieval by which early processes
      determine, on a trial-by-trial basis, if the task can be solved by the default
      semantic system. If not, there is a dynamic shift to cognitive control processes
      that guide retrieval from episodic memory.

PMID- 19109985
TI  - Preattentive surface and contour grouping in Kanizsa figures: evidence from
      parietal extinction.
AB  - Visual extinction commonly occurs after unilateral, parietal brain damage and
      manifests in a failure to identify contralesional stimuli when presented
      simultaneously with other, ipsilesional stimuli - but full awareness for single
      stimulus presentations. However, extinction can be substantially reduced when
      preattentive grouping operations link fragmentary items across hemifields into a
      coherent object. For instance, one study demonstrated preserved access to
      bilateral stimulus segments when these could be grouped to form a Kanizsa square
      [Mattingley, J. B., Davis, G., & Driver, J. (1997). Preattentive filling-in of
      visual surfaces in parietal extinction. Science, 275, 671-674]. Here, we
      investigated the relative contributions of distinct object attributes to the
      spared access in Kanizsa figure completion in extinction, by systematically
      varying the degree to which bilateral surface filling-in and contour
      interpolations group disparate items. We demonstrate that surface information can
      substantially reduce extinction, whereas contour completions showed comparably
      smaller influences. In summary, such graded influences of object attributes
      support recurrent models of grouping, first, linking fragmentary parts into
      coherent surfaces and, second, interpolating the precise boundaries.

PMID- 19109986
TI  - Parietal modules for reaching.
AB  - Optic ataxia (OA) is classically defined as a deficit of visually guided
      movements that follows lesions of the posterior part of the posterior parietal
      cortex (PPC). Since the formalisation of the double stream of visual information
      processing [Milner, A. D., & Goodale, M. A. (1995). The visual brain in action.
      Oxford: Oxford University Press] and the use of OA as an argument in favour of
      the involvement of the posterior parietal cortex (dorsal stream) in visually
      guided movements, many studies have looked at the visuomotor deficits of these
      patients. In parallel, the development of neuroimaging methods have led to
      increasing information about the role of the posterior parietal cortex in
      visually guided actions. In this article, we discuss the similarities and
      differences in the results that emerged from these two complementary viewpoints
      by combining a meta-analysis of neuroimaging data on reaching with lesion studies
      from OA patients and results of our own fMRI study on reaching in the ipsi- and
      contra-lateral visual field. We identified four bilateral parietal foci from the
      meta-analysis and found that the more posterior foci showed greater
      lateralisation for contralateral visual stimulation than more anterior ones
      Additionally, the more anterior foci showed greater lateralisation for the use of
      the contralateral hand than the more posterior ones. Therefore, we can
      demonstrate that they are organised along a postero-anterior gradient of visual
      to-somatic information integration. Furthermore, from the combination of imaging
      and lesion data it can be inferred that a lesion of the three most posterior foci
      responsible for the target-hand integration could explain the hand and field
      effect revealed in OA reaching behaviour.

PMID- 19109988
TI  - Structural identification by mass spectrometry of a novel antimicrobial peptide
      from the venom of the solitary bee Osmia rufa (Hymenoptera: Megachilidae).
AB  - The venom from the solitary bee Osmia rufa (Hymenoptera: Megachilidae) was
      analyzed using mass spectrometry (MS)-based techniques. Sensitive proteomic
      methods such as on-line LC-ESI-MS and nanoESI-MS analyses revealed more than 50
      different compounds with molecular masses ranging from 400 to 4000Da. The major
      component has a monoisotopic molecular mass of 1924.20Da and its amino acid
      sequence was elucidated by de novo sequencing using tandem mass spectrometry and
      Edman degradation. This 17-residue cysteine-free peptide, named osmin, shows some
      similarities with the mast cell degranulation (MCD) peptide family. Free acid and
      C-terminally amidated osmins were chemically synthesized and tested for
      antimicrobial and haemolytic activities. The synthetic C-amidated peptide (native
      osmin) was found to be about three times more haemolytic than its free acid
      counterpart, but both peptides are much less lytic than melittin from social bee
      venom. Preliminary antimicrobial and antifungal tests indicate that both peptides
      are able to inhibit bacterial and fungal growth at micromolar concentrations.

PMID- 19109987
TI  - Lung injury, inflammation and Akt signaling following inhalation of particulate
      hexavalent chromium.
AB  - Certain particulate hexavalent chromium [Cr(VI)] compounds are human respiratory
      carcinogens that release genotoxic soluble chromate, and are associated with
      fibrosis, fibrosarcomas, adenocarcinomas and squamous cell carcinomas of the
      lung. We postulate that inflammatory processes and mediators may contribute to
      the etiology of Cr(VI) carcinogenesis, however the immediate (0-24 h) pathologic
      injury and immune responses after exposure to particulate chromates have not been
      adequately investigated. Our aim was to determine the nature of the lung injury,
      inflammatory response, and survival signaling responses following intranasal
      exposure of BALB/c mice to particulate basic zinc chromate. Factors associated
      with lung injury, inflammation and survival signaling were measured in airway
      lavage fluid and in lung tissue. A single chromate exposure induced an acute
      immune response in the lung, characterized by a rapid and significant increase in
      IL-6 and GRO-alpha levels, an influx of neutrophils, and a decline in macrophages
      in lung airways. Histological examination of lung tissue in animals challenged
      with a single chromate exposure revealed an increase in bronchiolar cell
      apoptosis and mucosal injury. Furthermore, chromate exposure induced injury and
      inflammation that progressed to alveolar and interstitial pneumonitis. Finally, a
      single Cr(VI) challenge resulted in a rapid and persistent increase in the number
      of airways immunoreactive for phosphorylation of the survival signaling protein
      Akt, on serine 473. These data illustrate that chromate induces both survival
      signaling and an inflammatory response in the lung, which we postulate may
      contribute to early oncogenesis.

PMID- 19109989
TI  - Intense exercise potentiates oxidative stress in striatum of reserpine-treated
      animals.
AB  - Regular physical activity exerts beneficial effects for mental and physical
      health, but an intense exercise can cause oxidative stress (OS) in dopaminergic
      regions and intensify the harmful effects of reserpine. Reserpine-induced
      neurotoxicity can be accessed by behavioral and biochemical evaluations. The
      objective of this study was to examine the effect of a gradual intensifying
      exercise program on an animal model of oxidative stress. Male rats were submitted
      to swimming sessions (1 h/day, for eleven weeks), and they were loaded gradually
      during the adaptation period (two weeks) with a weight corresponding to 1-7% of
      their body weight tied to their back. After the last training, the animals were
      treated with two doses of vehicle or reserpine (1 mg/kg-sc), an agent that
      induces orofacial dyskinesia. After behavioral evaluations, the striatum was
      dissected for enzymatic and biochemical assays. Development of cardiac
      hypertrophy demonstrated the effectiveness of the physical training. The gradual
      intense exercise and reserpine increased lipid peroxidation and striatal catalase
      activity. The results confirm the importance of catalase activity in orofacial
      dyskinesia which can be related to lipid peroxidation in striatal dopaminergic
      brain tissue. These results indicate that intense exercise can have some
      deleterious effect on striatal dopaminergic system.

PMID- 19109990
TI  - A serpin from the parasitoid wasp Leptopilina boulardi targets the Drosophila
      phenoloxidase cascade.
AB  - The insect phenoloxidase (PO) cascade is known to be tightly regulated by serine
      proteases and serine protease inhibitors of the serpin family. As a key component
      of the insect immune system, it is also suspected to be inhibited by several
      endoparasitoid wasps, insects that develop inside other arthropods as hosts.
      However, the underlying mechanisms of this inhibition are largely undescribed.
      Here, we report the characterization of a gene encoding a serpin, LbSPNy, highly
      expressed in the venom of the wasp Leptopilina boulardi (IS(y) type), and we show
      that either the venom or the recombinant LbSPNy inhibit the PO cascade in the
      hemolymph of Drosophila yakuba host larva. Altogether, our results identify the
      first serpin used as a virulence factor by a parasitoid wasp and show that it
      disrupts the activation pathway of the PO in the Drosophila host.

PMID- 19109991
TI  - Functional impairment in aged rats chronically exposed to human range dietary
      aluminum equivalents.
AB  - Aluminum salts are ubiquitous in modern life. Yet, their possible adverse effects
      on human health remain to be determined. A longitudinal study was conducted in
      rats to assess whether chronic aluminum exposure at human-relevant dietary levels
      can alter performance on a hippocampal-dependent continuous alternation spatial
      memory discrimination T-maze task. From age 12 months onwards, three groups of
      rats trained to perform this task were chronically exposed to 0, 2, and 20ppm of
      aluminum in drinking water. When combined with the aluminum in their feed, these
      regimens resulted in approximately 0.4, 0.5 and 1.7mg aluminum (kg bodyweight
      day), designated as low, intermediate and higher aluminum doses. These levels are
      within the urban American dietary aluminum range. The rats were tested weekly
      during middle age (>or=12 to <24 months) and old age (>or=24 months) or until
      their terminal condition became apparent. Of the 30 rats that survived to at
      least 28 months, 0/10 on the lowest aluminum dose, 2/10 on the intermediate dose,
      and 7/10 on the higher dose attained significantly lower performance in old age
      than in middle age. Compared with rats whose T-maze performance remained intact,
      the rats with impaired performance had significantly higher serum aluminum levels
      (p<0.01) and cell counts indicating a larger percentage of aluminum-loaded
      pyramidal cells in their entorhinal cortex (p<0.05). Moreover, their percentage
      of aluminum-loaded entorhinal cortex cells correlated inversely with the decrease
      in their T-maze performance scores between middle age and old age (r=0.76,
      p<0.0005). The functionally-impaired rats also displayed aberrant behaviors
      including inability to focus attention on their task, perseverative activity, and
      incontinence while in the T-maze. Hence, in this longitudinal study, ingestion of
      0.5mg aluminum/(kg bodyweight day) or more, consumed throughout most of adult
      life led, in old age, to a slowly-progressing condition that impaired cognitive
      function in susceptible rats.

PMID- 19109992
TI  - VPAC and PAC receptors: From ligands to function.
AB  - Vasoactive intestinal peptide (VIP) and the pituitary adenylate cyclase
      activating polypeptides (PACAPs) share 68% identity at the amino acid level and
      belong to the secretin peptide family. Following the initial discovery of VIP
      almost four decades ago a substantial amount of knowledge has been presented
      describing the mechanisms of action, distribution and pleiotropic functions of
      these related peptides. It is now known that the physiological actions of these
      widely distributed peptides are produced through activation of three common G
      protein coupled receptors (VPAC(1), VPAC(2) and PAC(1)R) which preferentially
      stimulate adenylate cyclase and increase intracellular cAMP, although stimulation
      of other intracellular messengers, including calcium and phospholipase D, has
      been reported. Using a range of in vitro and in vivo approaches, including cell
      based functional assays, transgenic animals and rodent models of disease,
      VPAC/PAC receptor activation has been associated with numerous physiological
      processes (e.g. control of circadian rhythms) and clinical conditions (e.g.
      pulmonary hypertension), which underlies on-going research efforts and makes
      these peptides and their cognate receptors attractive targets for the
      pharmaceutical industry. However, despite the considerable interest in VPAC/PAC
      receptors and the processes which they mediate, there is still a paucity of
      selective and available, non-peptide ligands, which has hindered further advances
      in this field both at the basic research and clinical level. This review
      summarises the current knowledge of VIP/PACAP and the VPAC/PAC receptors with
      regard to their distribution, pharmacology, signalling pathways, splice variants
      and finally, the utility of animal models in exploring their physiological roles.

PMID- 19109994
TI  - A multi-component decomposition algorithm for event-related potentials.
AB  - Event-related potentials (ERPs) are evoked activities of the brain related to
      specific events. They can be estimated by averaging across many trials aligned to
      a specific event onset time point, such as the stimulus, the response, or other
      behaviorally significant markers. If a single trial includes more than one such
      event (marker), as in all reaction-time tasks, the cross-contamination of
      components related to different events may mislead the explanation of ERPs. In
      order to recover event-related components, Zhang [Zhang J. Decomposing stimulus
      and response component waveforms in ERP. Journal of Neuroscience Methods
      1998;80:49-63] provided a method for decomposing of ERPs according to two markers
      (stimulus and the behavioral response). Here we extend this formulation to deal
      with three or more markers in a single trial, and recover individual ERP
      components that are time-locked to those markers. As an application, we analyzed
      a cuing experiment with three events: cue, stimulus and response. The elapse
      between cue and stimulus was varied from trial to trial by the experimenter, and
      the time between stimulus and response was determined by the subjects (reaction
      time variation). Our decomposition results show that the cue-dependent component
      waveform turns out to flatten out 500 ms after cue-onset, a finding consistent
      with our experimental paradigm.

PMID- 19109993
TI  - Current status of inverse agonism at serotonin2A (5-HT2A) and 5-HT2C receptors.
AB  - Contemporary receptor theory was developed to account for the existence of
      constitutive activity, as defined by the presence of receptor signaling in the
      absence of any ligand. Thus, ligands acting at a constitutively active receptor,
      can act as agonists, antagonists, and inverse agonists. In vitro studies have
      also revealed the complexity of ligand/receptor interactions including agonist
      directed stimulus trafficking, a finding that has led to multi-active state
      models of receptor function. Studies with a variety of cell types have
      established that the serotonin 5-HT(2A) and 5-HT(2C) receptors also demonstrate
      constitutive activity and inverse agonism. However, until recently, there has
      been no evidence to suggest that these receptors also demonstrate constitutive
      activity and hence reveal inverse agonist properties of ligands in vivo. This
      paper describes our current knowledge of constitutive activity in vitro and then
      examines the evidence for constitutive activity in vivo. Both the serotonin 5
      HT(2A) and 5-HT(2C) receptors are involved in a number of physiological and
      behavioral functions and are the targets for treatment of schizophrenia, anxiety,
      weight control, Parkinsonism, and other disorders. The existence of constitutive
      activity at these receptors in vivo, along with the possibility of inverse
      agonism, provides new avenues for drug development.

PMID- 19109995
TI  - A method for the study of the effects of combining multiple pseudorandom
      fusimotor stimulation on the responses of muscle-spindle primary-ending
      afferents.
AB  - We describe a new method of investigation of the integrative action of fusimotor
      inputs in mammalian muscle spindles by stimulation of multiple fusimotor axons
      using independent pseudorandom pulse trains, each of low mean rate with
      pseudorandomly distributed stimulus intervals. Technically it was feasible only
      because of the development of (1) a novel, highly efficient approach to
      functional isolation of fusimotor efferents in ventral-root filaments, which we
      have called the isodyne strategy; (2) a real-time, microprocessor-based stimulus
      artefact cancellation device (SACAD); and (3) a highly adjustable, multi-branch
      stimulation electrode array. The general approach of using multiple, independent,
      pseudorandom stimulation of several input channels has wider applications in
      controlled-activation paradigms.

PMID- 19109996
TI  - Automatic determination of the optimal shape of a surface electrode: selective
      stimulation.
AB  - We present a method for automatic determination of the shape and position of the
      surface electrode for selective control of fingers extension and flexion by means
      of electrical stimulation. The multi-pad electrodes used in the experiments
      comprised 24 pads (1cm diameter) distributed over an area (7 cm x 10 cm)
      positioned over dorsal and volar aspects of the forearm. The four-channel
      stimulation system for grasping comprised also an oval reference electrode over
      the carpal tunnel, and two oval electrodes over the thenar and thumb extensor
      muscles. We measured seven angles: proximal inter-phalangeal and metacarpal
      phalangeal index and ring finger joint rotations, wrist extension/flexion and
      ulnar/radial rotation, and pronation/supination of the forearm. The optimal
      electrode was determined as the combination of pads that led to fingers, wrist
      and forearm rotations being similar to the trajectories of healthy individuals
      when grasping. The similarity of trajectories was assessed by analyzing the
      aggregate error defined as the sum of squares of differences between the angles
      measured when stimulating the forearm in tetraplegics and the angles measured in
      healthy individuals. The aggregate errors were determined from measurements
      during sequential stimulation of each of the 24 pads. The analysis comprised hand
      opening and closing for palmar and lateral grasps. The time for determining the
      optimal electrode was about 10 min. The optimal electrodes had different branched
      shapes in each of the six tetraplegics; however, once determined they remained
      unchanged when tested on different days.

PMID- 19109997
TI  - Novel vibrotactile discrimination task for investigating the neural correlates of
      short-term learning with fMRI.
AB  - Innovative perceptual-motor learning paradigms applicable for functional magnetic
      resonance imaging (fMRI) offer much potential for elucidating the specific
      cortical mechanisms that underpin short-term learning. In this study, a novel,
      fMRI-compatible, vibrotactile discrimination task, adapted from a tactile version
      of the Morse-code, was introduced. Uniquely, this task featured distinct
      components of training and testing, such that cortical changes associated with
      these modalities of learning may be dissociated. During testing, the ability to
      correctly associate matching and non-matching vibrotactile/visual stimulus pairs
      was assessed. Initial testing in naive healthy subjects (n = 23) revealed a
      training-dependent decrease in discrimination error rates and discrimination
      reaction time over the course of a single fMRI session. The rate and extent of
      learning were significantly decreased when the complexity of vibrotactile stimuli
      to be discriminated was increased. In a subgroup of subjects (n = 15) who
      participated in repeated testing, it was revealed that both initial testing and
      retesting sessions were characterized by similar within-subject training-related
      behavioral properties, when different vibrotactile patterns of similar challenge
      level were presented for the retesting session. Preliminary functional imaging
      data from a single subject case-study revealed task-related cortical activations
      over a widely distributed frontoparietal network, which demonstrated spatial
      consistency within- and also between-sessions (test-retest). Observed behavioral
      and cortical properties suggest that the current methodology may be suitable for
      assessing neural changes linked to short-term vibrotactile learning. In addition,
      demonstrated test-retest capability of the proposed task may uniquely permit
      applications where test conditions are to be manipulated within-subjects.

PMID- 19109998
TI  - A simple and rapid method to collect the cerebrospinal fluid of rats and its
      application for the assessment of drug penetration into the central nervous
      system.
AB  - Many central nervous system (CNS) drug discovery programs require the successful
      collection of cerebrospinal fluid (CSF) for assessing CNS penetration and
      distribution of new chemical entities. The objective of the present investigation
      was to simplify the technique for collecting maximum CSF from cisterna magna of
      the rats. Rat was anesthetized with 5% halothane and positioned in a stereotaxic
      frame. The rat head was flexed downward at approximately 45 degrees , a
      depressible surface with the appearance of a rhomb between occipital
      protuberances and the spine of the atlas becomes visible. The 23 G needle was
      punctured into the cisterna magna for CSF collection without making any incision
      at this region. The blunt end of the needle was inserted into a 10 in. length of
      PE-50 tubing and other end of the tubing was connected to a collection syringe.
      The non-contaminated sample was drawn into the syringe by simple aspiration. This
      technique is simple and can be performed by one person. The technique has a
      greater than 95% success rate of CSF collection and it was free of red blood cell
      contamination. In addition, it yielded 100-120 microL of CSF per rat. This method
      is simple, effective, and easy to perform and has been successfully applied in
      preclinical screening of novel chemical entities in neuropharmacotherapy for CNS
      use. The present method is demonstrated by studying the CSF concentrations of
      carbamazepine and raclopride.

PMID- 19110000
TI  - Formation of subviral particles of the capsid protein VP2 of infectious bursal
      disease virus and its application in serological diagnosis.
AB  - Infectious bursal disease virus (IBDV) is an immunosuppressive disease of young
      chicken characterized by severe depletion of B-lymphocytes in the bursa of
      Fabricius. To provide antigen for diagnostic tests, its major structural protein
      VP2 was expressed in the yeast Saccharomyces cerevisiae. Electron microscopy of
      purified VP2 protein demonstrated that when expressed from yeast cells VP2
      protein forms subviral particles (SVPs) of approximately 20nm in diameter. A
      recombinant VP2 antigen-based single serum dilution enzyme linked immunosorbent
      assay (ELISA) using the SVPs detected IBDV specific antibodies in chickens. A
      linear relationship was found between the predicted antibody titres at a single
      working dilution of 1:1000 and the corresponding observed serum titres when
      determined by the standard serial dilution method. Regression analysis was used
      to construct a standard curve from which an equation was derived which confirmed
      their correlation. The equation was then used to convert the corrected absorbance
      readings of the single working dilution directly into the predicted ELISA
      antibody titres. The assay proved to be sensitive, specific and accurate as
      compared to the serum neutralization test and agar gel immunodiffusion test. The
      recombinant VP2 antigen is a suitable alternative to whole viral antigen.

PMID- 19109999
TI  - Rapid and sensitive detection of 68 unique varicella zoster virus gene
      transcripts in five multiplex reverse transcription-polymerase chain reactions.
AB  - Varicella zoster virus (VZV) becomes latent in ganglionic neurons along the
      entire neuraxis. Although all predicted VZV open reading frames (ORFs) have been
      detected by macroarray and microarray analysis in virus-infected cells in culture
      where virus gene expression is abundant, array technology does not detect all VZV
      gene transcripts in latently infected human ganglia, where the abundance of
      ganglionic RNA is low and VZV gene transcription is highly variable. Using
      reverse transcription-polymerase chain reaction (RT-PCR) and the GenomeLab
      Genetic Analysis System (GeXPS), transcripts mapping to all 68 predicted unique
      VZV ORFs were detected in VZV-infected MeWo cells. Oligonucleotide primers
      contained both VZV- and cell-specific sequences linked to universal DNA sequences
      such that PCR amplification products were of predetermined sizes. Amplification
      products were resolved by capillary gel electrophoresis and detected by
      fluorescence spectrophotometry. Serial dilutions of total RNA extracted from VZV
      infected MeWo cells were analyzed in parallel by GeXPS multiplex RT-PCR and real
      time RT-PCR. GeXPS technology detected as few as 20 copies of VZV gene-specific
      transcripts. Only five multiplex RT-PCR assays were needed to analyze the entire
      VZV transcriptome. This technology will allow rapid analysis of all VZV genes
      transcribed during latency in human ganglia.

PMID- 19110001
TI  - Levocetirizine inhibits rhinovirus-induced ICAM-1 and cytokine expression and
      viral replication in airway epithelial cells.
AB  - Levocetirizine inhibits the production of intercellular adhesion molecule (ICAM)
      1 and secretion of interleukin (IL)-6 and IL-8, which may have beneficial effects
      on the pathophysiologic changes related to human rhinovirus (HRV) infection. We
      investigated the effects of levocetirizine on rhinovirus infection in primary
      human nasal epithelial cells (HNEC) and A549 cells. Cells were treated with
      different concentrations of levocetirizine, ranging from 0.5, 5 or 50nM, either
      starting at the time of infection and continuing thereafter, or beginning 24h
      before infection and continuing thereafter. Levocetirizine treatment inhibited
      the HRV-induced increase in ICAM-1 mRNA and protein levels, as well as the HRV
      induced expression of IL-6 and IL-8 mRNA and protein levels. Viral titer, as
      measured by culture in MRC-5 cells, was reduced by levocetirizine. Levocetirizine
      treatment also reduced the increased nuclear factor-kappa B (NF-kappaB)
      expression seen with HRV infection. Levocetirizine inhibited the expression of
      Toll-like receptor (TLR)3 mRNA and protein levels. These findings indicate that,
      in HNEC and A549 cells, levocetirizine inhibits HRV replication and HRV-induced
      upregulation of ICAM-1, IL-6, and IL-8, TLR3 expression and NF-kappaB activation.
      The results of this study suggest that levocetirizine may have a possible
      clinical application in the treatment of airway inflammation caused by HRV
      infection.

PMID- 19110002
TI  - Recombinant fowlpox virus vector-based vaccine completely protects chickens from
      H5N1 avian influenza virus.
AB  - With the widespread presence of influenza virus H5N1 in poultry and wildlife
      species, particularly migrating birds, vaccination has become an important
      control strategy for avian influenza (AI). In this study, the immune efficacy and
      hemagglutination inhibition (HI) antibody responses induced by a recombinant
      fowlpox virus (FPV) vector-based rFPV-HA-NA vaccine was evaluated in SPF and
      commercial chickens. Four-week old SPF chickens vaccinated with one dose of
      vaccine containing 2 x 10(3) plaque forming units (PFU) of virus were completely
      protected from H5N1 AI virus 1 week after vaccination, and protective immunity
      lasted for at least 40 weeks. Two-week old commercial layer chickens were
      vaccinated with the rFPV-HA-NA vaccine and boosted with the same dose of vaccine
      following an interval of 18 weeks. The HI antibody titers higher than 4log2
      lasted for 52 weeks after the booster immunization. We also examined the efficacy
      of the rFPV-HA-NA vaccine in SPF chickens administrated by different routes. The
      results showed that effective application of rFPV-HA-NA vaccine in poultry may be
      restricted to wing-web puncture, intramuscular or subcutaneous injection. These
      results demonstrate that the rFPV-HA-NA vaccine is effective in the prevention of
      infection of H5N1 AI virus.

PMID- 19110004
TI  - Adolescent anabolic-androgenic steroid exposure alters lateral anterior
      hypothalamic serotonin-2A receptors in aggressive male hamsters.
AB  - Chronic anabolic-androgenic steroid (AAS) treatment during adolescence
      facilitates offensive aggression in male Syrian hamsters (Mesocricetus auratus).
      Serotonin (5-HT) modulates aggressive behavior and has been shown to be altered
      after chronic treatment with AAS. Furthermore, 5-HT type 2 receptors have been
      implicated in the control of aggression. For example, treatment with 5-HT(2A)
      receptor antagonists suppress the generation of the offensive aggressive
      phenotype. However, it is unclear whether these receptors are sensitive to
      adolescent AAS exposure. The current study assessed whether treatment with AAS
      throughout adolescence influenced the immunohistochemical localization of 5
      HT(2A) in areas of the hamster brain implicated in the control of aggression.
      Hamsters were administered AAS (5.0 mg/kg) each day throughout adolescence,
      scored for offensive aggression, and then examined for differences in 5-HT(2A)
      immunoreactivity (5-HT(2A)-ir). When compared with non-aggressive oil-treated
      controls, aggressive AAS-treated hamsters showed significant increases in 5
      HT(2A)-ir fibers in the lateral portion of the anterior hypothalamus (LAH).
      Further analysis revealed that AAS treatment also produced a significant increase
      in the number of cells expressing 5-HT(2A)-ir in the LAH. Together, these results
      support a role for altered 5-HT(2A) expression and further implicate the LAH as a
      central brain region important in the control of adolescent AAS-induced offensive
      aggression.

PMID- 19110003
TI  - Behavioral effects of systemic transforming growth factor-alpha in Syrian
      hamsters.
AB  - The growth factor, transforming growth factor-alpha (TGF-alpha) is strongly
      expressed in the hypothalamic circadian pacemaker, the suprachiasmatic nucleus
      (SCN). TGF-alpha is one of several SCN peptides recently suggested to function as
      a circadian output signal for the regulation of locomotor activity rhythms in
      nocturnal rodents. When infused in the brain, TGF-alpha suppresses activity. TGF
      alpha suppresses other behaviors as well including feeding, resulting in weight
      loss. Elevated TGF-alpha is correlated with some cancers, and it is possible the
      TGF-alpha and its receptor, the epidermal growth factor receptor (EGFR), mediate
      fatigue and weight loss associated with cancer. If true for cancers outside of
      the brain, then systemic TGF-alpha should also affect behavior. We tested this
      hypothesis in hamsters with intraperitoneal injections or week-long subcutaneous
      infusions of TGF-alpha. Both treatments suppressed activity and infusions caused
      reduced food consumption and weight loss. To identify areas of the brain that
      might mediate these effects of systemic TGF-alpha, we used immunohistochemistry
      to localize cells with an activated MAP kinase signaling pathway (phosphorylated
      ERK1). Cells were activated in two hypothalamic areas, the paraventricular
      nucleus and a narrow region surrounding the third ventricle. These sites could
      not only be targets of TGF-alpha produced in the SCN but could also mediate
      effects of elevated TGF-alpha from tumors both within and outside the central
      nervous system.

PMID- 19110005
TI  - Decreased anxiety-like behavior and locomotor/exploratory activity, and
      modulation in hypothalamus, hippocampus, and frontal cortex redox profile in
      sexually receptive female rats after short-term exposure to male chemical cues.
AB  - Chemical cues are widely used for intraspecific social communication in a vast
      majority of living organisms ranging from bacteria to mammals. As an example,
      mammals release olfactory cues with urine that promote neuroendocrine modulations
      with changes in behavior and physiology in the receiver. In this work, four-month
      old Wistar (regular 4-day cyclic) virgin female rats were utilized in the
      proestrus-to-estrus phase of the reproductive cycle for experimental exposure. In
      an isolated room, female rats were exposed for 90 min to male-soiled bedding
      (MSB). Elevated plus-maze assay, open field test, and light/dark box task were
      performed to analyze behavioral alterations on females after exposure. For
      biochemical assays, female rats were killed and the hypothalamus, hippocampus,
      and frontal cortex were isolated for further analysis. Antioxidant enzyme
      activities (superoxide dismutase, catalase and glutathione peroxidase), non
      enzymatic antioxidant defense measurements (TRAP and TAR), and the oxidative
      damage parameters (TBARS, Carbonyl and SH content) were analyzed. In behavioral
      analyses we observe that female rats show decreased anxiety and
      locomotory/exploratory activities after MSB exposure. In biochemical assays we
      observed an increase in both enzymatic and non-enzymatic antioxidant defenses in
      different central nervous system (CNS) structures analyzed 30 and 90 min after
      MSB exposure. Furthermore, hippocampus and frontal cortex showed diminished free
      radical oxidative damage at 180 and 240 min after exposure. These results provide
      the first evidence that oxidative profile of female CNS structures are altered by
      chemical cues present in the MSB, thus suggesting that pheromonal communication
      is able to modulate radical oxygen species production and/or clearance in the
      female brain.

PMID- 19110006
TI  - Neural circuits subserving behavioral flexibility and their relevance to
      schizophrenia.
AB  - Impairments in different forms of behavioral flexibility, such as set-shifting
      and reversal learning, are some of the most reliable cognitive deficits
      associated with schizophrenia, and have been attributed to a disruption in
      frontal lobe functioning. However, recent animal studies have highlighted the
      distinct functional roles that different subcortical systems interconnected with
      the prefrontal cortex (PFC) play in different forms of behavioral flexibility.
      This suggests that dysfunction in these circuits also contribute to the cognitive
      impairments in these processes observed in schizophrenia. The present review
      summarizes findings from studies that utilize or rodent studies rodents to
      elucidate the dissociable contributions that prefrontal cortical, striatal,
      thalamic and dopaminergic systems make to different component processes of
      behavioral flexibility, with an emphasis on set-shifting functions mediated by
      the medial PFC. We also review recent work investigating how different
      manipulations thought to model certain aspects of schizophrenia affect set
      shifting and reversal learning. Lastly, we report novel data describing the
      effects of subchronic ketamine exposure on these forms of flexibility. Ketamine
      treatment reduced perseverative tendencies during set-shifting, but impaired
      reversal learning, suggesting a complex disruption of neural circuits related to
      the nucleus accumbens shell and orbitofrontal cortex. Viewed collectively, these
      findings further our understanding of how certain neural abnormalities observed
      in the schizophrenic brain may relate to impairments in behavioral flexibility.
      This information may facilitate the development of animal models that resemble
      the complex disruptions in neural circuitry observed in schizophrenia, which
      would aid in the discovery of novel targeted pharmacotheraputic approaches to
      ameliorate cognitive dysfunction linked to these circuits.

PMID- 19110007
TI  - An overview of the Babesia, Plasmodium and Theileria genomes: a comparative
      perspective.
AB  - Babesia, Plasmodium and Theileria form a triad of apicomplexan hemoparasites and
      are accountable for significant mortality and morbidity to humans and animals
      globally. Understanding the pathobiology of these three genera is crucial as
      multiple drug resistant strains continue to arise in endemic areas along with
      pesticide and acaricide resistant vector hosts. Vastly improved sequencing
      technology has produced whole genome sequences of several apicomplexan species
      and subsequent comparative analyses of these genomes have identified unique as
      well as common features among the different species, information that will help
      in the pursuit of alternative therapies, management and perhaps elimination of
      the disease. This review, therefore, summarizes comparisons of genome structure,
      protein families, metabolic pathways and organelle biology in these three
      apicomplexans and how such knowledge has and will continue to enhance the field.

PMID- 19110008
TI  - Control of gene expression in Plasmodium falciparum - ten years on.
AB  - Ten years ago this journal published a review with an almost identical title
      detailing how the then recent introduction of transfection technology had
      advanced our understanding of the molecular control of transcriptional processes
      in Plasmodium falciparum, particularly in terms of promoter structure and
      function. In the succeeding years, sequencing of several Plasmodium spp. genomes
      and application of high throughput global postgenomic technologies have proven as
      significant, if not more, as has the ability to genetically manipulate these
      parasites in dissecting the molecular control of gene expression. Here we aim to
      review our current understanding of the control of gene expression in P.
      falciparum, including evidence available from other Plasmodium spp. and
      apicomplexan parasites. Specifically, however, we will address the current
      polarised debate regarding the level at which control is mediated, and attempt to
      identify some of the challenges this field faces in the next 10 years.

PMID- 19110009
TI  - Fetuin-A and arterial stiffness in patients with normal kidney function.
AB  - AIM: To evaluate the association between fetuin-A level (AHSG), its encoding gene
      (Thr256Ser) and arterial function in subjects with normal kidney function.
      INTRODUCTION: The aortic pulse wave velocity (aPWV) is a predictor for
      cardiovascular mortality. Fetuin-A is a calcification inhibitor and correlates
      negatively with increased vascular stiffness in dialysis patients. The fetuin-A
      polymorphism (Thr256Ser) is associated with reduced fetuin levels and accelerated
      vascular calcification in dialysis patients. Little is known about the role of
      fetuin-A as an independent predictor for the development of arterial stiffness in
      healthy subjects. MATERIALS AND METHODS: We studied 116 subjects with normal
      kidney function (age 47+/-12 years, 50 females and 66 males) of the FLEMENGHO
      study. Calcium measurements, plasma fetuin-A, its encoding gene (Thr256Ser) and
      indexes of arterial stiffness, such as aPWV and arterial distensibility, were
      determined. RESULTS: Fetuin-A levels were negatively correlated with aPWV (r=
      0.21, p=0.029). After an adjustment for multiple covariables, fetuin-A levels
      were independently associated with aPWV (r=-0.30, p=0.022) in males but not in
      females. Male fetuin-A SerSer carrier had lower fetuin-A levels and higher aPWV
      (fetuin-A: 61.9+/-29.0 microg/ml; aPWV: 14.3+/-0.9 m/s) as compared to ThrThr
      (fetuin-A: 109.9+/-54.9 microg/ml; aPWV: 6.4+/-1.3 m/s) and ThrSer carrier
      (fetuin-A: 100.8+/-52.5 microg/ml; aPWV: 6.6+/-1.3 m/s). Other calcium variables
      were not significantly associated with arterial stiffness. CONCLUSION: With
      respect to common calcium variables, only fetuin-A level showed an inverse
      relation with aPWV in men with normal renal function. Male fetuin-A SerSer
      carriers demonstrate particularly high aortic stiffness, possibly implying a
      status of increased cardiovascular risk.

PMID- 19110010
TI  - Inhibition of extracellular signal-regulated kinase (ERK) signaling participates
      in repression of nuclear factor (NF)-kappaB activity by glucocorticoids.
AB  - Glucocorticoid (GC) effects are mediated via the GC-receptor (GR), which either
      stimulates or represses gene expression. Repression of target genes often
      involves negative cross-talk between the GR and other transcription factors e.g.
      NF-kappaB, important for gene activation. Using HEK293 cells we here describe
      that repression of NF-kappaB requires functions of the GR that are dependent on
      the signaling pathways employed to activate NF-kappaB. While a GR mutant was able
      to repress NF-kappaB activity following activation by TNFalpha, it did not so
      following activation by the phorbol ester TPA. In these cells, TPA stimulation
      but not TNFalpha, activated extracellular signal-regulated kinase (ERK). We
      demonstrated that the ability of the dexamethasone activated GR mutant to repress
      TPA-induced NF-kappaB activity was restored in conjunction with ERK1/2
      inhibition. Previous reports have shown GC-mediated inhibition of ERK1/2
      phosphorylation to involve GC induction of MAPK phosphatase-1 (MKP-1). Here, we
      demonstrated that the GRR488Q mutant was incapable of inducing gene expression of
      endogenous MKP-1 following dexamethasone treatment, in contrast to the GRwt.
      However, TPA treatment alone resulted in much stronger MKP-1 expression in both
      GRwt and GRR488Q containing cells than that of dexamethasone suggesting that the
      inability of GRR488Q to inhibit TPA-induced NF-kappaB activity did not involve a
      lack of MKP-1 expression. In line with this, RNAi targeted towards MKP-1 did not
      abolish or inhibit the ability of the GRwt to repress NF-kappaB activity.
      Importantly, we observed no difference in activated ERK1/2 (phospho-ERK1/2)
      expression over time between GRwt and GRR488Q containing cells following co
      treatment with TPA and dexamethasone. Based on these results we suggest that GRwt
      does not directly regulate ERK1/2 but rather alters ERK1/2-mediated effects
      allowing it to repress NF-kappaB activity, a capacity lacked by the GRR488Q
      mutant.

PMID- 19110011
TI  - S100B's double life: intracellular regulator and extracellular signal.
AB  - The Ca2+-binding protein of the EF-hand type, S100B, exerts both intracellular
      and extracellular functions. Recent studies have provided more detailed
      information concerning the mechanism(s) of action of S100B as an intracellular
      regulator and an extracellular signal. Indeed, intracellular S100B acts as a
      stimulator of cell proliferation and migration and an inhibitor of apoptosis and
      differentiation, which might have important implications during brain, cartilage
      and skeletal muscle development and repair, activation of astrocytes in the
      course of brain damage and neurodegenerative processes, and of cardiomyocyte
      remodeling after infarction, as well as in melanomagenesis and gliomagenesis. As
      an extracellular factor, S100B engages RAGE (receptor for advanced glycation end
      products) in a variety of cell types with different outcomes (i.e. beneficial or
      detrimental, pro-proliferative or pro-differentiative) depending on the
      concentration attained by the protein, the cell type and the microenvironment.
      Yet, RAGE might not be the sole S100B receptor, and S100B's ability to engage
      RAGE might be regulated by its interaction with other extracellular factors.
      Future studies using S100B transgenic and S100B null mice might shed more light
      on the functional role(s) of the protein.

PMID- 19110012
TI  - Examining the exercise-affect dose-response relationship: does duration influence
      frontal EEG asymmetry?
AB  - The "feel better" effect of exercise has been well established, but the specific
      influence of exercise duration on affect has not been systematically studied from
      a multi-level measurement approach. Such an approach offers the opportunity to
      assess psychophysiological responses that relate to psychological state. One
      relevant response is the change in frontal brain processes indexed by anterior
      EEG asymmetry, which is related to approach-withdrawal orientation and affective
      state [Davidson, R.J., 1993. Cerebral asymmetry and emotion: conceptual and
      methodological conundrums. Cogn. Emot. 7, 138; Davidson, R.J., 1998. Anterior
      electrophysiological asymmetries, emotion, and depression: Conceptual and
      methodological conundrums. Psychophysiology 35(5), 607-614.]. To examine the
      relationship between exercise duration and affective response, as well as the
      role of frontal brain processes in this relationship, female undergraduate
      students (N=16, VO(2) max=35.93 ml kg(-1) min(-1), aged 19-23 yrs) were assessed
      for frontal EEG and self-reported affective responses, as measured by the Profile
      of Mood States (POMS), following rest and three different durations of exercise
      (15, 30 and 45 min) performed at a standardized intensity (i.e., just below the
      ventilatory threshold (VT)). Psychological vigor and frontal EEG asymmetry
      following exercise of 30 min were elevated compared to that observed following
      rest and other exercise durations (i.e., 15, 45 min). The results support a dose
      response relationship between exercise duration and affect characterized by an
      inverted-U. Furthermore, the covariance analysis, conducted to assess the role of
      cortical activation at the homologous sites in the post-exercise affective
      response, suggests that the enhanced vigor observed after 30 min of exercise
      results from the reduction of withdrawal-oriented processes rather than the
      facilitation of approach-oriented processes.

PMID- 19110013
TI  - A novel statistical analysis of voltage-imaging data by structural time series
      modeling and its application to the respiratory neuronal network.
AB  - The respiratory neuronal network activity can be optically recorded from the
      ventral medulla of the in vitro brainstem-spinal cord preparation using a voltage
      sensitive dye. To assess the synchronicity between respiratory-related neurons
      and the breath-by-breath variability of respiratory neuronal activity from
      optical signals, we developed a novel method by which we are able to analyze
      respiratory-related optical signals without cycle-triggered averaging. The model,
      called the sigmoid and transfer function model, assumes a respiratory motor
      activity as the output and optical signals of each pixel as the input, and
      activity patterns of respiratory-related regions are characterized by estimated
      model parameter values. We found that rats intermittently showing multi-peaked
      respiratory motor activities had a relatively low appearance frequency of
      respiratory-related pixels. Further, correlations between respiratory-related
      pixels in rats with such unstable respiratory motor activities were poor. The
      poor correlations were caused by respiratory neurons recruited in the late
      inspiratory phase. These results suggest that poor synchronicity between
      respiratory neurons, which are recruited at various timings of inspiration,
      causes intermittent multi-peaked respiratory motor output. In conclusion,
      analyses of respiratory-related optical signals without cycle-triggered averaging
      are feasible by using the proposed method. This approach can be widely applied to
      the analysis of event-related optical signals.

PMID- 19110014
TI  - Prefrontal and medial temporal contributions to episodic memory-based reasoning.
AB  - Episodic memory retrieval and reasoning are fundamental psychological components
      of our daily lives. Although previous studies have investigated the brain regions
      associated with these processes separately, the neural mechanisms of reasoning
      based on episodic memory retrieval are largely unknown. Here, we investigated the
      neural correlates underlying episodic memory-based reasoning using functional
      magnetic resonance imaging (fMRI). During fMRI scanning, subjects performed three
      tasks: reasoning, episodic memory retrieval, and episodic memory-based reasoning.
      We identified dissociable activations related to reasoning, episodic memory
      retrieval, and linking processes between the two. Regions related to reasoning
      were identified in the left ventral prefrontal cortices (PFC), and those related
      to episodic memory retrieval were found in the right medial temporal lobe (MTL)
      regions. In addition, activations predominant in the linking process between the
      two were found in the left dorsal and right ventral PFC. These findings suggest
      that episodic memory-based reasoning is composed of at least three processes,
      i.e., reasoning, episodic memory retrieval, and linking processes between the
      two, and that activation of both the PFC and MTL is crucial in episodic memory
      based reasoning. These findings are the first to demonstrate that PFC and MTL
      regions contribute differentially to each process in episodic memory-based
      reasoning.

PMID- 19110015
TI  - The cell adhesion molecule L1 controls growth cone navigation via ankyrin(B)
      dependent modulation of cyclic AMP.
AB  - During development, asymmetric Ca(2+) signals across the growth cone mediate
      bidirectional axon guidance depending on intracellular levels of cyclic AMP:
      Ca(2+) signals trigger attractive or repulsive turning when cyclic AMP levels are
      high or low, respectively. Here, we report that the cell adhesion molecule L1
      elevates cyclic AMP levels in neurons via ankyrin(B), a protein that links the L1
      cytoplasmic tail with the spectrin network. We also show that the loss of
      ankyrin(B) expression converts Ca(2+)-triggered attraction to repulsion when the
      growth cone migrates via an L1-dependent mechanism. These results indicate that
      ankyrin(B) regulates axon guidance via cyclic AMP.

PMID- 19110016
TI  - Suitable transmembrane domain significantly increase the surface-expression level
      of Fc(epsilon)RIalpha in 293T cells.
AB  - Evidence showed that the extracellular part of Fc(epsilon)RIalpha (FCR) with its
      own transmembrane domain (TMF) cannot be expressed as a transmembrane form in CHO
      cell line. However, FCR could be displayed on cell surface with the transmembrane
      domain (TM) of human IL2Ralpha (TMI). Theoretical analysis of TMF and TMI using
      TM prediction methods showed that TMI possessed strong orientation tendency to
      form "outside to inside" transmembrane mode from N-terminal to C-terminal, while
      TMF was prone to form "inside to outside" mode. Based on the analyzing results,
      the TM of Her2 (TMH) was studied and showed similar transmembrane mode as that of
      TMI, which implied that TMH might be a novel TM to obtain the surface display of
      FCR. Then, DNA sequences encoding TMH and TMF were fused to 3'-end of FCR gene,
      respectively. Fluorescent microscope observation indicated that FCR_TMH seemed to
      be located mainly on cell surface, while FCR_TMF appeared in endochylema. Flow
      cytometry analysis and Western blot also showed that the surface expression of
      FCR was enhanced significantly by TMH, while FCR_TMF could not be surface
      displayed in 293T cell. The experimental results were consistent with the
      theoretical predictions and demonstrated that the orientation tendency of TM may
      be very important in subcellular location of proteins.

PMID- 19110017
TI  - Activity of TAR in inducible inhibition of HIV replication by foamy virus vector
      expressing siRNAs under the control of HIV LTR.
AB  - In this report we describe foamy virus vectors with conditional expression of
      short interfering RNAs (siRNAs) in HIV infected cells. Short hairpin RNAs
      (shRNAs) based on two targets in the 5' end of the untranslated region and one in
      the rev gene flanked with 5' and 3' microRNA 30 (miR30) sequences were
      synthesized and placed under the control of an HIV promoter for Tat-mediated
      expression. HIV permissive cells were transduced with foamy virus vectors
      containing each hybrid shRNA expression cassette and tested for their efficacy on
      the inhibition of HIV replication. Effective Tat dependent expression of the
      shRNAs, as well as GFP placed downstream each shRNA was evident. In addition the
      results show inhibition of HIV replication by greater than 98%. Interestingly,
      transduction of cells with a vector lacking an shRNA also revealed GFP expression
      in the presence of Tat with similar levels of inhibition of virus replication.
      When the TAR region was removed from this vector there was neither reduction in
      virus replication nor Tat-induced GFP expression. These results suggest that TAR
      in the vector, which Tat interacts to promote expression of the shRNA, is a
      potent inhibitor of virus replication. Previous studies with TAR regulated
      expression of antiviral genes ignore the contribution of TAR in the repression of
      virus replication. Interpretation of effective inhibition of HIV replication by
      antiviral genes located downstream of TAR while neglecting the efficacy of a
      potent repression by TAR is misleading.

PMID- 19110019
TI  - Fruit and vegetable consumption in children and their mothers. Moderating effects
      of child sensory sensitivity.
AB  - A cross-sectional study was carried out to ascertain the relative contribution of
      food neophobia and taste sensitivity to the amount of fruit and vegetables
      consumed in a typical day by 73, 2-5-year-old children attending nurseries in the
      South Birmingham area, UK. Sensory processing, parental control, child food
      neophobia and fruit and vegetable (FV) consumption of both mothers and children
      were measured. Parental and child FV consumption in the sample were positively
      associated (p<0.001). Moderated regression analyses showed that taste/smell
      sensitivity, but not food neophobia or tactile sensitivity, moderated the
      relationship between maternal and child FV consumption. In particular, children
      who were sensitive to taste/smell stimuli ate fewer fruit and vegetables,
      regardless of their mothers FV consumption. This finding implies that those
      children, who are sensitive to taste/smell stimuli, may be less likely to model
      maternal FV consumption. For these children, a more gradual route to encouraging
      acceptance, with attention to small sensory changes in foods, may be necessary to
      increase FV consumption.

PMID- 19110018
TI  - Dexamethasone-pDMAEMA polymeric conjugates reduce inflammatory biomarkers in
      human intestinal epithelial monolayers.
AB  - The mucoadhesive polymer, poly(dimethylamino)ethyl methacrylate, (pDMAEMA), was
      synthesised by living radical polymerisation and subsequently conjugated by
      quaternisation reaction to a functionalised anti-inflammatory corticosteroid
      dexamethasone, to separately yield two conjugates with either 9:1 or 18:1 molar
      ratios of dexamethasone:polymer respectively. The hypothesis was to test whether
      the active agent maintained in vitro bioactivity when exposed to the apical side
      of human intestinal epithelial monolayers, Caco-2 and mucus-covered HT29-MTX-E12
      (E12). HPLC analysis indicated high conjugate purity. Similar to pDMAEMA,
      fluorescently-labelled dexamethasone-pDMAEMA conjugates were bioadhesive to Caco
      2 and mucoadhesive to E12. Apical addition of conjugates suppressed mRNA
      expression of the inflammatory markers, NURR1 and ICAM-1 in E12 following
      stimulation by PGE(2) and TNF-alpha, respectively. Conjugates also suppressed TNF
      alpha stimulated cytokine secretion to the basolateral side of Caco-2 monolayers.
      Measurement of dexamethasone permeability from conjugates across monolayers
      suggested that conjugation reduced permeability compared to free dexamethasone.
      LDH assay indicated that conjugates were not cytotoxic to monolayers. Anti
      inflammatory agents can therefore be successfully conjugated to polymers and they
      retain adhesion and bioactivity and have potential to be formulated for topical
      administration.

PMID- 19110020
TI  - The effect of fruit in different forms on energy intake and satiety at a meal.
AB  - Consuming whole fruit reduces ratings of satiety more than fruit juice, but
      little is known about the effects of different forms of fruit on subsequent
      energy intake. This study tested how consuming preloads of apples in different
      forms prior to a meal (apple, applesauce, and apple juice with and without added
      fiber) influences satiety and energy intake at meal. Preloads were matched for
      weight, energy content, energy density, and ingestion rate. Once a week for 5
      weeks, 58 adults consumed one of four preloads (266 g; 125 kcal [523 kJ]), or no
      preload (control), followed by a test meal consumed ad libitum 15 min later.
      Results showed that eating apple reduced lunch energy intake (preload+test meal)
      by 15% (187+/-36 kcal [782+/-151 kJ]) compared to control (p<0.0001) and
      decreased energy intake compared to applesauce and both juices. Fullness ratings
      differed significantly after preload consumption (apple>applesauce>both
      juices>control). Overall, whole apple increased satiety more than applesauce or
      apple juice. Adding naturally occurring levels of fiber to juice did not enhance
      satiety. These results suggest that solid fruit affects satiety more than pureed
      fruit or juice, and that eating fruit at the start of a meal can reduce energy
      intake.

PMID- 19110021
TI  - Human dendritic cell maturation and activation by a heat-killed recombinant yeast
      (Saccharomyces cerevisiae) vector encoding carcinoembryonic antigen.
AB  - Tumor-associated antigens are weakly immunogenic. Human carcinoembryonic antigen
      (CEA) is overexpressed on a wide range of human carcinomas and represents an
      attractive target for cancer immunotherapy. This study analyzes the ability of a
      Saccharomyces cerevisiae vector containing the transgene encoding CEA (yeast-CEA)
      to activate human dendritic cells (DCs) and stimulate CEA-specific T-cell
      responses. We demonstrate for the first time that treatment with yeast-CEA can
      activate human DCs, resulting in increases in surface expression of CD80, CD83,
      CD54, CD58, and MHC class II, and increased production by DCs of IL-12p70, TNF
      alpha, IFN-gamma, IL-8, IL-2, IL-13, IL-10, and IL-1beta. We also show that human
      DCs treated with yeast-CEA can activate CEA-specific T-cell lines and can act as
      antigen-presenting cells (APCs) to generate CEA-specific T-cell lines capable of
      lysing CEA(+) human tumor cells. Gene expression profiles of human DCs treated
      with yeast-CEA show increased expression of numerous genes involved in the
      production of chemokines and cytokines and their receptors, and genes related to
      antigen uptake, antigen presentation, and signal transduction.

PMID- 19110022
TI  - HPLC-based quantification of haemagglutinin in the production of egg- and MDCK
      cell-derived influenza virus seasonal and pandemic vaccines.
AB  - The haemagglutinin (HA) content is an important specification of influenza
      vaccines. Recently, a reversed-phase high performance liquid chromatography (RP
      HPLC) method for quantification of HA in PER.C6 cell culture-based whole virus
      vaccines has been reported, having a high sensitivity, precision, broad range,
      and high sample throughput [Kapteyn JC, Drissi Saidi M, Dijkstra R, Kars C, Tjon
      CMS-K, Weverling GJ et al. Haemagglutinin quantification and identification of
      influenza A&B strains propagated in PER.C6 cells: a novel RP-HPLC method. Vaccine
      2006;24:3137-44]. This RP-HPLC assay is based on measuring the peak area of HA1,
      the hydrophilic subunit of HA, which turned out to be proportional to the amount
      of HA analyzed. Here, we present data demonstrating that this RP-HPLC method is
      also highly suitable for HA quantification of active and BPL- or formaldehyde
      inactivated egg-based and MDCK cell-based whole virus samples, including egg
      allantoic harvest, and in final (monovalent) subunit vaccines, including those
      for pandemic H5N1 strains and for virosomal vaccines. In addition, the RP-HPLC
      assay was demonstrated to be a very powerful tool in the early stages of seasonal
      influenza vaccine production, when homologous serial radial immunodiffusion
      (SRID) reagents are not yet available, enabling fast and reliable viral growth
      studies in eggs in order to select the best growing virus strains or reassortants
      for the production of the seasonal trivalent influenza vaccine. Because of its
      high sensitivity, the RP-HPLC assay has shown its enormous value in supporting
      small scale MDCK-based (H5N1) influenza virus production models. Finally, the
      observed differences between HA1 molecules from various HA subtypes in UV
      absorbance, FLD response, and in the actual retention times in RP-HPLC are
      discussed in relation to the primary structure of the HA1 molecules studied.

PMID- 19110023
TI  - T-cell-derived cytokines, nitric oxide production by peripheral blood monocytes
      and seric anti-Leishmania (Leishmania) chagasi IgG subclass patterns following
      immunization against canine visceral leishmaniasis using Leishvaccine and
      Leishmune.
AB  - It is generally accepted that distinct cytokine expression by the cellular immune
      response plays a critical role during the outcome of experimental as well as
      natural canine visceral Leishmaniasis (CVL). Despite the fact that
      immunoprophylaxis of CVL has become an important control strategy and protective
      immunity has been reported upon immunization with whole as well as purified
      Leishmania antigens, the cytokine profile of T-cells triggered by anti-CVL
      vaccines still remain to be determined. Herein, we have developed a cross
      sectional analysis of German Shepherd dogs submitted to vaccination protocols
      with Leishvaccine (n=6) and Leishmune (n=6). Our data identified distinct
      immunological profiles elicited by Leishvaccine and Leishmune, with the
      Leishvaccine triggering a mixed, IFN-gamma and IL-4, cytokine pattern in addition
      to high levels of anti-Leishmania IgG1, whereas the Leishmune induced an
      immunological pattern characterized by enhanced levels of IFN-gamma, NO and anti
      Leishmania chagasi IgG2. It was important to notice that despite the distinct
      immunological patterns triggered by Leishvaccine and Leishmune, the ability of
      both immunobiologicals to activate T-cell-derived IFN-gamma synthesis further
      suggesting their immunogenic potential against CVL. These findings added support
      to our hypothesis that both antigenic composition (whole antigen in Leishvaccine
      versus purified antigen in Leishmune) as well as the adjuvant nature (BGC and
      saponin) used for the vaccine formulation may count for the distinct activation
      pattern observed.

PMID- 19110024
TI  - Hazard to the developing male reproductive system from cumulative exposure to
      phthalate esters--dibutyl phthalate, diisobutyl phthalate, butylbenzyl phthalate,
      diethylhexyl phthalate, dipentyl phthalate, and diisononyl phthalate.
AB  - Phthalate esters are found in a wide variety of consumer and food packing
      products. Hence there is widespread exposure of the human population to these
      chemicals. Some of the phthalate esters are known to be toxic to the developing
      male reproductive system. This paper derives a reference dose (RfD) for each of
      the phthalate esters (dibutyl phthalate, diisobutyl phthalate, butylbenzyl
      phthalate, diethylhexyl phthalate, dipentyl phthalate, and diisononyl phthalate)
      that cause these effects. As these phthalate esters cause similar adverse
      biological effects and have the same mechanism of action, it is appropriate in a
      risk assessment to consider the potential adverse effects from cumulative
      exposure to these chemicals using a dose addition model. This paper provides
      examples of a cumulative risk assessment using the hazard index and relative
      potency approaches from the RfDs derived from studies in laboratory animals and
      exposure information in people. The results of the cumulative risk assessments
      for both a US and a German population show that the hazard index is below one.
      Thus it is unlikely that humans are suffering adverse developmental effects from
      current environmental exposure to these phthalate esters.

PMID- 19110025
TI  - Effect of R3487/MEM3454, a novel nicotinic alpha7 receptor partial agonist and 5
      HT3 antagonist on sustained attention in rats.
AB  - It is well established that nicotinic systems in the brain are critically
      involved in attentional processes in both animals and humans. The current study
      assessed the effects of a novel nicotinic alpha7 receptor partial agonist and 5
      HT3 antagonist, R3487/MEM3454 (also referred to as R3487 or MEM 3454) on
      sustained attention in rats performing an operant visual signal detection task.
      The effects of R3487/MEM3454 were compared to those of the acetylcholinesterase
      inhibitor/nicotinic alpha7 allosteric positive modulator galanthamine. Adult
      female Sprague-Dawley rats were injected subcutaneously with R3487/MEM3454 (0.03,
      0.1, 0.15, 0.3 and 0.6 mg/kg), galanthamine (0.25, 0.5, 1, 2 mg/kg) or vehicle 30
      min before the attentional test. In the second study, the time-dependent effects
      of R3487/MEM3454 were assessed by injecting the compound (0.6 mg/kg, s.c.) at
      different pretreatment intervals (30, 60 or 90 min) before the start of the
      attentional task. Our results show a significant dose-effect for R3487/MEM3454 on
      percent hit accuracy performance without any significant alteration on percent
      correct rejection performance. In the time-dependent test, R3487/MEM3454
      significantly increased the percent hit accuracy performance when animals were
      injected 60 min before the start of the attentional task. Administration of
      galanthamine failed to significantly increase percent hit accuracy performance
      and increasing the dose of galanthamine produced a decrease in percent correct
      rejection performance. The present findings with R3487/MEM3454 suggest that
      nicotinic alpha7 receptors and/or 5-HT3 receptors may play an important role in
      modulating sustained attention and that R3487/MEM3454 may have therapeutic
      potential in improving sustained attention in humans.

PMID- 19110026
TI  - Effects of fluoxetine and venlafaxine on serum brain derived neurotrophic factor
      levels in depressed patients.
AB  - BACKGROUND: Several studies demonstrated that depressed patients had low serum
      BDNF levels which correlated with the severity of their depression, and
      antidepressant treatment increases levels of serum BDNF in depressed patients. It
      was speculated that agents acting on both noradrenergic and serotonergic
      transporters might have a greater influence on BDNF levels. The aim of our study
      was to determine effects of venlafaxine vs. fluoxetine on serum BDNF levels in
      depressive patients. METHODS: Forty-three patients diagnosed as major depressive
      disorder according to DSM-IV are included in the study. Forty-three patients were
      randomized to take fluoxetine (22 cases) or venlafaxine (21 cases). Serum levels
      of BDNF were measured by ELISA at baseline and 6 weeks after the start of
      treatment. RESULTS: Baseline levels of BDNF were not significantly different
      between the patient group and the controls. But male patients and the male
      controls showed statistical differences with respect to baseline BDNF levels.
      BDNF levels of the patient group did not change with treatment. Yet, the increase
      of BDNF levels was close to statistically significant in the fluoxetine group,
      whereas not significant in the venlafaxine group. There were no significant
      differences in baseline and 6th week BDNF levels between the responders and the
      non-responders. CONCLUSION: Further studies controlling for a wide variety of
      confounding variables are needed, which may help to reach a clear conclusion
      about the potential of BDNF as a biomarker for depression or as a predictor of
      antidepressant efficacy.

PMID- 19110027
TI  - Effects of the food contaminant semicarbazide following oral administration in
      juvenile Sprague-Dawley rats.
AB  - Semicarbazide (SEM) is an azodicarbonamide by-product present in glass jar
      packaged foods including babyfoods, in bleaching steps and flour treatment.
      Experimental data showed SEM acting as osteolathyrogen agent, but few
      toxicological data are available in susceptible life-stages. This study aimed to
      evaluate effects of SEM oral administration for 28 days at 0, 40, 75, 140 mg/kg
      bw day during the juvenile period in Sprague-Dawley rats. Histopatological
      examinations of: epiphyseal cartilage - potential target of SEM lathyrogen action
      - testes, ovary, uterus, thyroid, thymus, spleen, adrenals, representative of the
      main developing organs relevant to juvenile toxicity, and neurobehavioural tests
      in males, were performed. Mortality at high and mid dose levels and significantly
      decreased body weight gain were observed in males even at the lowest dose. Lack
      of mineralization in cartilage at all dose levels was present. Marked alterations
      of spontaneous motor and exploratory behaviours were evident even at 40 mg/kg.
      Histological alterations were observed in all tissues; thyroid and ovary effects
      were present also at 40 mg/kg. The present study indicate that the NOAEL in
      juvenile rats is lower than 40 mg/kg for SEM oral administration. SEM
      administration during juvenile period exerted pleiotropic effects and further
      studies are suggested to elucidate mechanisms.

PMID- 19110028
TI  - An integrated metabonomic method for profiling of metabolic changes in carbon
      tetrachloride induced rat urine.
AB  - Carbon tetrachloride (CCl(4)) is a well-known model compound for inducing
      chemical hepatic injury. This work characterizes the metabolism disorders of
      hepatotoxicity induced by CCl(4) in a Wistar rat model with a single dosage of 1
      ml/kg. A seven-day long continuous collection of urine was performed in male rats
      in this experiment. Blood biochemistry and histopathology were examined to
      identify specific changes of liver hepatotoxicity. At the same time, an
      integrated analytical approach based on liquid chromatography coupled with mass
      spectrometry (LC-MS) was developed to map the metabolic response in urine. The
      current metabonomic approach based on LC-MS indicated 23 endogenous metabolites
      as biomarkers in urine associated with the hepatotoxicity induced by CCl(4). The
      underlying regulations of CCl(4)-perturbed metabolic pathways were discussed
      according to the identified metabolites. The present study proves the great
      potential of LC-MS based metabonomics in mapping metabolic response for
      toxicology.

PMID- 19110030
TI  - Homocysteine modulates sodium channel currents in human atrial myocytes.
AB  - Hyperhomocysteinemia has been proposed as an important risk factor for cardiac
      arrhythmias and ischemia worldwide. However, the cellular mechanism underlying
      toxic effects of homocysteine on hearts remains conjectural. It is well known
      that aberrant sodium channels can promote the development of cardiac arrhythmias
      and ischemic injury. So the present study was to investigate toxic effects of
      homocysteine on sodium currents recorded in human atrial cells. Human atrial
      myocytes were acutely enzymatically isolated and the whole-cell patch clamp
      technique was employed to record sodium currents and membrane potential in human
      atrial cells in the absence and presence of homocysteine. We found that in human
      atrial myocytes, sodium currents were significantly increased by pathological
      concentration of homocysteine with the maximum activation potential shifted
      toward the positive potential. However, physiological concentration of
      homocysteine did not have any effects on sodium currents. The time constants for
      time-dependent activation (tau(act)) and inactivation (tau(inact)) of sodium
      currents were both markedly shortened by elevated homocysteine levels. The
      further channel kinetic data showed that elevated homocysteine levels shifted the
      inactivation curve towards positive potential and accelerated the recovery from
      inactivation of sodium channel, but did not affect the activation of sodium
      channel. Additionally, the resting membrane potential of human atrial myocytes
      was obviously depolarized by elevated homocysteine levels in the current clamp
      model. Taken together, the data presented in this study first revealed that
      increased homocysteine levels caused the abnormality of sodium currents in human
      atrial cells by slowing the inactivation and promote the recovery of sodium
      channels, which provides a better understanding of hyperhomocysteinemia
      associated cardiac arrhythmias and ischemia.

PMID- 19110029
TI  - Ciglitazone induces apoptosis via activation of p38 MAPK and AIF nuclear
      translocation mediated by reactive oxygen species and Ca(2+) in opossum kidney
      cells.
AB  - We have previously demonstrated that the synthetic peroxisome proliferator
      activated receptor-gamma (PPARgamma) agonist ciglitazone induces apoptosis
      accompanied by activation of p38 mitogen-activated protein kinase (MAPK) and
      nuclear translocation of apoptosis inducing factor (AIF) in opossum kidney (OK)
      renal epithelial cells. However, the precise mechanism by which ciglitazone
      induces activation of p38 MAPK and the role of AIF in the induction of the
      apoptosis are not defined. This study was therefore undertaken to determine
      whether the roles of reactive oxygen species (ROS) generation and intracellular
      Ca(2+) in the ciglitazone-induced activation of p38 MAPK and whether AIF nuclear
      translocation is responsible for the ciglitazone-induced apoptosis in OK renal
      epithelial cells. Ciglitazone caused generation of ROS and an increase in
      intracellular Ca(2+). Ciglitazone-induced cell death was reduced by the
      antioxidant Trolox, the Ca(2+) chelator EGTA, and the store-operated Ca(2+)
      channels (SOCC) blocker lanthanum chloride (La(3+)), indicating involvement of
      ROS and Ca(2+) in the ciglitazone-induced cell death. Ciglitazone-induced
      intracellular Ca(2+) increase was decreased by Trolox, while ROS generation was
      not affected by EGTA and La(3+), suggesting that ROS generation promote the
      increase of intracellular Ca(2+). Transfection of small interfering RNA (siRNA)
      of p38 MAPK or vector expressing microRNA (miRNA) of AIF prevented the
      ciglitazone-induced cell death. Activation of p38 MAPK, mitochondrial membrane
      depolarization, and AIF nuclear translocation induced by ciglitazone were
      inhibited by Trolox, EGTA and La(3+). Taken together, these results suggest that
      ROS-dependent intracellular Ca(2+) increase is responsible for activation of p38
      MAPK and nuclear translocation of AIF by ciglitazone.

PMID- 19110031
TI  - Cell-specific loss of kappa-opioid receptors in oligodendrocytes of the
      dysmyelinating jimpy mouse.
AB  - Jimpy is a murine mutation in myelin proteolipid protein, leading to premature
      death of oligodendrocytes and severe central nervous system hypomyelination.
      Jimpy is a bona fide model of human Pelizaeus-Merzbacher disease. This paper
      describes a severe reduction in expression of kappa-opioid receptors (KOP) in
      oligodendrocytes of jimpy mice. A cell-specific reduction of >90% is apparent by
      5 days of age. Expression is not reduced in neurons, and mu-opioid receptor
      expression is normal. Mechanism(s) leading to deficient KOP expression in jimpy
      mice remain unclear. We speculate that loss of KOP may be related to increased
      [Ca(2+)](i) and premature death of jimpy oligodendrocytes.

PMID- 19110032
TI  - Effects of fluoxetine on the rat brain in the forced swimming test: a [F-18]FDG
      micro-PET imaging study.
AB  - We used the [F-18]FDG micro-PET neuroimaging to examine the effects of fluoxetine
      on brain activity in rats and on their behavioral response in the forced swimming
      test (FST). In the first experiment, the rats were administered doses of
      fluoxetine (10 or 20mg/kg) 24, 19 and 1h before the rat brains were scanned.
      Fluoxetine induced strong activation of the dorsal hippocampus and the
      deactivation of the inferior colliculus, medulla oblongata, and prelimbic cortex
      in a dose-dependent manner. These results seemed to be related with the changes
      in 5-HT (5-hydroxytryptamine, serotonin) levels after selective serotonin
      reuptake-inhibitor treatments. In the second experiment, the changes in glucose
      metabolism in the test session were measured after fluoxetine was given between
      pre-test and test sessions of the FST. Fluoxetine administration significantly
      decreased immobility behavior compared with saline administration. At the same
      time, the activity of the insular/piriform cortex decreased significantly. In
      contrast, the extent of cerebellar activation increased. The glucose metabolism
      of the dorsal hippocampus also increased, which suggests that post-stress changes
      in the facilitation of hippocampal serotonergic neurotransmission lead to
      decreased immobilization in the FST.

PMID- 19110033
TI  - Bax-inhibiting peptide protects glutamate-induced cerebellar granule cell death
      by blocking Bax translocation.
AB  - Glutamate-induced excitotoxicity has been implicated in the pathogenesis of
      various neurological damages and disorders. In the brain damage of immature
      animals such as neonatal hypoxic-ischemic brain injury, the excitotoxicity
      appears to be more intimately involved through apoptosis. Bax, a member of the
      Bcl-2 family proteins, plays a key role in the promotion of apoptosis by
      translocation from the cytosol to the mitochondria and the release of apoptogenic
      factors such as cytochrome c. Recently, Bax-inhibiting peptide (BIP), a novel
      membrane-permeable peptide which can bind Bax in the cytosol and inhibit its
      translocation to the mitochondria, was developed. To investigate the possibility
      of a new neuroprotection strategy targeting Bax translocation in glutamate
      induced neuronal cell death, cerebellar granule neurons (CGNs) were exposed to
      glutamate with or without BIP. Pretreatment of CGNs with BIP elicited a dose
      dependent reduction of glutamate-induced neuronal cell death as measured by MTT
      assay. BIP significantly suppressed both the number of TUNEL-positive cells and
      the increase in caspases 3 and 9 activities induced by glutamate. In addition,
      immunoblotting after subcellular fractionation revealed that BIP prevented the
      glutamate-induced Bax translocation to the mitochondria and the release of
      cytochrome c from the mitochondria. These results suggest that agents capable of
      inhibiting Bax activity such as BIP might lead to new drugs for glutamate-related
      diseases in the future.

PMID- 19110034
TI  - Generalizability of perturbation-evoked cortical potentials: Independence from
      sensory, motor and overall postural state.
AB  - Following disturbances to postural stability, balance recovery reactions are
      evoked by numerous sensory inputs and characterized by motor reactions involving
      different patterns of activity, depending on postural task conditions. It remains
      unknown whether well-documented cortical responses to instability share common
      spatio-temporal characteristics, despite variations in the sensory, motor, and
      postural components of the reactions. The objective was to explore the spatio
      temporal profile of cortical potentials evoked by instability requiring either
      upper- or lower-limb compensatory responses. The hypothesis that upper- and lower
      limb balance-correcting reactions are associated with evoked cortical potentials
      (N1, P2) featuring similar spatio-temporal characteristics was tested by inducing
      postural perturbations in seated (SIT) or standing (STAND) positions. For both
      conditions, N1 amplitude was greatest at FCz, with no significant differences in
      the timing of N1 peak (SIT: 142.4+/-7.95ms; STAND: 148.4+/-4.10ms) or N1
      amplitude (SIT: 37.16+/-6.99microV; STAND: 39.08+/-4.51microV). The amplitude of
      the P2 potential (measured at CPz) was significantly larger in the STAND
      condition (37.87+/-6.14microV) than in the SIT (23.66+/-6.21microV) condition.
      Significant differences in P2 peak time between tasks were absent (SIT: 319.9+/
      11.45ms; STAND: 322.7+/-7.61ms). Though differences in the amplitude of
      components of evoked potentials may reflect the extent of cortical involvement in
      different aspects of postural control, similarities in the spatio-temporal
      components of cortical potentials between tasks reflects generalizable cortical
      processing of unexpected stimuli independent of the sensory, motor, or postural
      aspects of the response.

PMID- 19110035
TI  - Stimulation of basolateral amygdaloid serotonin 5-HT(2C) receptors promotes the
      induction of long-term potentiation in the dentate gyrus of anesthetized rats.
AB  - We have previously found that the induction of hippocampal long-term potentiation
      (LTP) is modulated by neuron activities in the basolateral amygdala (BLA).
      However, little is known about what neurotransmitter system in the BLA
      contributes to modulation of hippocampal LTP. In the present study, we
      investigated possible involvement of BLA serotonergic system in the induction of
      LTP at the perforant path (PP)-dentate gyrus (DG) granule cell synapses of
      anesthetized rats. The induction of PP-DG LTP was significantly inhibited by
      intra-BLA injection of the 5-HT(2) receptor antagonist cinanserin (25-50nmol),
      but not by intra-BLA injection of the 5-HT(1,7) receptor antagonist methiothepin
      (50nmol), the 5-HT(3) receptor antagonist ondansetron (50nmol) or the 5-HT(4)
      receptor antagonist RS23597-190 (100nmol). In addition, intra-BLA injection of
      the 5-HT(2C) receptor agonist MK212 (50nmol) facilitated the induction of PP-DG
      LTP. These results suggest that the induction of PP-DG LTP is promoted by
      activation of 5-HT(2C) receptors in the BLA.

PMID- 19110036
TI  - AMPA glutamate receptor subunits 1 and 2 regulate dendrite complexity and spine
      motility in neurons of the developing neocortex.
AB  - Within neurons of several regions of the CNS, mature dendrite architecture is
      attained via extensive reorganization of arbor during the developmental period.
      Since dendrite morphology determines the firing patterns of the neuron,
      morphological refinement of dendritic arbor may have important implications for
      mature network activity. In the neocortex, a region of brain that is sensitive to
      activity-dependent structural rearrangement of dendritic arbor, the proportion of
      AMPA receptors increases over the developmental period. However, it is unclear
      whether changes in AMPA receptor expression contribute to maturation of dendritic
      architecture. To determine the effects of increasing AMPA receptor expression on
      dendrite morphology and connectivity within the neocortex, and to determine
      whether these effects are dependent on specific AMPA receptor subunits, we
      overexpressed the AMPA glutamate receptor subunit 1 (GluR1) and glutamate
      receptor subunit 2 (GluR2) in cultured rat neocortical neurons at the time that
      AMPA receptors would normally be incorporated into synapses. Following expression
      of GluR1 or GluR2 we observed increases in the length and complexity of dendritic
      arbor of cortical neurons, and a concurrent reduction in motility of spines. In
      addition, expression of either subunit was associated with an increased density
      of excitatory postsynaptic puncta. These results suggest that AMPA receptor
      expression is an important determinant of dendrite morphology and connectivity in
      neocortical neurons, and further, that contrary to other regions of the CNS, the
      effects of AMPA receptors on dendrite morphology are not subunit-specific.

PMID- 19110037
TI  - Activation of CB1 cannabinoid receptors impairs memory consolidation and
      hippocampal polysialylated neural cell adhesion molecule expression in contextual
      fear conditioning.
AB  - We investigated the role of CB1 receptors in hippocampal-dependent memory
      consolidation mediated by polysialylated neural cell adhesion molecule (PSA-NCAM)
      during contextual fear conditioning (CFC). The CB1 receptor agonist 3-(1,1
      dimethylheptyl)-(-)-11-hydroxy-Delta(8)-tetrahydrocannabinol (HU-210) (0.1 mg/kg)
      was given immediately after training during the memory consolidation phase, and
      freezing behavior was measured 24 h after conditioning. Administration of HU-210
      attenuated freezing behavior measured in CFC. Western blot analysis showed that
      CFC induced a decrease in the expression of NCAM-180, but did not change the
      level of NCAM-140 and increased PSA-NCAM expression measured 24 h after training
      in the rat hippocampus. HU-210 (0.1 mg/kg) injection did not affect the reduction
      in NCAM-180 levels induced by CFC, but it blocked the increase in PSA-NCAM
      expression. Since the dentate gyrus (DG) of the hippocampus is known to be
      involved in memory consolidation and expresses a high level of PSA-NCAM protein,
      we measured the effects of CFC and HU-210 administration on PSA-NCAM
      immunoreactive (IR) cells in the DG. CFC caused an increase in the number of PSA
      NCAM-IR cells in the DG, but not K(i)-67- or doublecortin (DCX)-IR cells. This
      increase in PSA-NCAM-IR cells was abolished by HU-210 injection. Administration
      of the CB1 receptor antagonist N-(piperidin-1-yl)-5-(4-iodophenyl)-1-(2,4
      dichlorophenyl)-4-methyl-1H-pyrazole-3-carboxamide (AM-251) (3 mg/kg immediately
      before HU-210) inhibited the effects of HU-210 on freezing behavior and PSA-NCAM
      expression in the DG. These results indicate that activation of CB1 receptors
      disturbs consolidation of fear memory in CFC, likely by affecting PSA-NCAM
      expression in the DG, which plays an important role in synaptic rearrangement
      during the formation of memory traces.

PMID- 19110038
TI  - Effect of "enriched environment" during development on adult rat behavior and
      response to the dopamine receptor agonist apomorphine.
AB  - Enriched housing conditions (enriched environment, EE) during development has
      been shown to influence adult rat behavior and transmitter systems, especially
      dopamine function. We were interested in how different degrees of enrichment
      during development would affect adult rats' behavior and response to dopamine
      receptor challenge. Two groups of male Wistar rats (n=11-12) were raised under
      two different degrees of EE, i.e. "high enriched" and "low enriched" groups. A
      third group was kept under standard conditions and served as "non-enriched"
      control. As adults, rats were tested for anxiety (elevated plus-maze), for
      spatial learning (four-arm-baited eight-arm radial maze), and for motivation
      (breakpoint of the progressive ratio test). Finally, locomotor activity (activity
      box) and sensorimotor gating (prepulse inhibition (PPI) of the acoustic startle
      response (ASR)) were tested with and without challenge with the dopamine receptor
      agonist apomorphine. The time spent on the open or enclosed arms of the elevated
      plus-maze did not differ between groups, but the high enriched group showed
      higher rearing activity on the open arms. The breakpoint did not differ between
      groups. Learning and memory in the radial maze task only differed on the first
      few trials, but high enriched rats run faster compared with the other groups. In
      contrast, in the activity box enriched groups were less active, but apomorphine
      had the highest effect. Between groups, no difference in PPI and startle
      amplitude was found, but in the high and low EE group startle amplitude was
      enhanced after administration of apomorphine, while the PPI deficit induced by
      this drug was not different between groups. Altogether, we found no evidence that
      different amounts of environmental enrichment without differences in social EE
      affect rats' cognitive, emotional or motivational behavior. However, motor
      activity seems to be enhanced when rats are behaviorally or pharmacologically
      challenged by dopamine receptor agonists.

PMID- 19110039
TI  - Modulation of AMPA currents by D(1)-like but not D(2)-like receptors in spinal
      motoneurons.
AB  - Dopamine can modulate and excite spinal locomotor networks, affect afferent
      transmission and increase motoneuronal excitability. One of the mechanisms
      whereby dopamine increases motoneuronal excitability is to potentiate AMPA
      channel-mediated glutamatergic transmission onto motoneurons. However, it is not
      known which dopaminergic receptor subtypes or the intracellular mechanisms
      contribute to these effects. In this study, we used whole-cell patch clamp
      techniques to record chemically evoked AMPA currents in neonatal mouse
      motoneurons. Bath application of D(1)-like receptor agonist (SKF 39383) increased
      the AMPA current amplitude and prolonged the decay time constant. In the presence
      of D(1) receptor antagonist LE300, the effects of DA on AMPA currents were
      blocked. In contrast, bath-application of the D(2)-like receptor agonist
      quinpirole did not modulate AMPA currents. In the presence of D(2) receptor
      antagonist L-741626, dopaminergic modulation of AMPA currents was unaffected.
      These results suggest that augmentation of AMPA transmission by dopamine is
      accomplished by D(1) receptor-based mechanisms. This short-term modulation does
      not appear to involve cycling of AMPA receptor into the membrane, since blocking
      insertion with botulinum toxin C did not affect the augmentation of AMPA currents
      after activating D(1) receptors. On the other hand, blocking protein kinase A
      (PKA) with H-89 completely abolished the effects of D(1) agonists. In addition,
      we used cell-attached single channel recording to demonstrate that stimulating
      D(1) receptors increased individual AMPA channel open probability and open
      duration. Our data demonstrate that dopamine increases the efficacy of
      glutamatergic transmission onto motoneurons by increasing AMPA conductances via a
      D(1) PKA-based signaling system.

PMID- 19110040
TI  - Signaling mechanisms mediating muscarinic enhancement of GABAergic synaptic
      transmission in the spinal cord.
AB  - Activation of muscarinic acetylcholine receptors (mAChRs) inhibits spinal
      nociceptive transmission by potentiation of GABAergic tone through M(2), M(3),
      and M(4) subtypes. To study the signaling mechanisms involved in this unique
      mAChR action, GABAergic spontaneous inhibitory postsynaptic currents (sIPSCs) of
      lamina II neurons were recorded using whole-cell patch clamp techniques in rat
      spinal cord slices. The mAChR agonist oxotremorine-M caused a profound increase
      in the frequency of GABAergic sIPSCs, which was abolished in the Ca(2+)-free
      solution. Inhibition of voltage-gated Ca(2+) channels with Cd(2+) and Ni(2+)
      largely reduced the effect of oxotremorine-M on sIPSCs. Blocking nonselective
      cation channels (NSCCs) with SKF96365 or 2-APB also largely attenuated the effect
      of oxotremorine-M. However, the KCNQ channel blocker XE991 and the adenylyl
      cyclase inhibitor MDL12330A had no significant effect on oxotremorine-M-induced
      increases in sIPSCs. Furthermore, the phosphoinositide-3-kinase (PI3K) inhibitor
      wortmannin or LY294002 significantly reduced the potentiating effect of
      oxotremorine-M on sIPSCs. In the spinal cord in which the M(3) subtype was
      specifically knocked down by intrathecal small interfering RNA (siRNA) treatment,
      SKF96365 and wortmannin still significantly attenuated the effect of oxotremorine
      M. In contrast, SKF96365 and wortmannin both failed to alter the effect of
      oxotremorine-M on sIPSCs when the M(2)/M(4) mAChRs were blocked. Therefore, our
      study provides new evidence that activation of mAChRs increases synaptic GABA
      release through Ca(2+) influx and voltage-gated Ca(2+) channels. The PI3K-NSCC
      signaling cascade is primarily involved in the excitation of GABAergic
      interneurons by the M(2)/M(4) mAChRs in the spinal dorsal horn.

PMID- 19110041
TI  - Novel interferon delta genes in mammals: cloning of one gene from the sheep, two
      genes expressed by the horse conceptus and discovery of related sequences in
      several taxa by genomic database screening.
AB  - Interferons (IFNs) are cytokines of vertebrates with many biological effects
      including antiviral, immunoregulatory and antiproliferative activities. Among
      them, mammalian type I IFNs represents a large family of related proteins, mainly
      virus-inducible, divided in 10 distinct subfamilies named alpha, beta, omega,
      delta, epsilon, alphaomega, nu, tau, kappa and zeta (or Limitin). Some type I IFN
      subfamilies are physiologically expressed by the conceptus during early pregnancy
      in ungulates. This is the case in ruminants with IFN-tau (which triggers the
      maintenance of the maternal corpus luteum during early pregnancy) and in the pig
      with IFN-delta, a type I IFN that was, until now, only described in this species
      (Lefevre, F. and Boulay, V., 1993; Lefevre, F., Guillomot, M., D'Andrea, S.,
      Battegay, S. and La Bonnardiere, C., 1998a) and whose biological role in early
      maternal-fetal interactions is unknown. We present here definitive evidences that
      IFN-delta is actually more widely represented among mammals. We report the
      cloning of three genes coding for non-porcine and biologically active IFN-deltas:
      one from the sheep, named OvIFN-delta, and two from the horse, named EqIFN-delta1
      and EqIFN-delta2. Interestingly, OvIFN-delta (139 aa) appears to be the shortest
      natural type I IFN presently known. Moreover, we identified by genomic database
      screening nineteen potentially functional IFN-delta genes from various species
      belonging to the four mammalian lineages (Afrotheria, Xenarthra, Euarchontoglires
      and Laurasiatheria). These novel type I IFNs display a high rate of identity with
      previously known porcine IFN-deltas. Phylogenetic analysis indicates that the
      newly defined IFN-delta family includes murine Limitin/IFN-zeta, their closest
      neighbor, but is clearly distinct from all other type I families. We also show
      that, although OvIFN-delta gene transcripts are not detectable in Day-14 and Day
      15 sheep conceptuses, the two equine genes are expressed by the horse conceptus
      tissues at the beginning of pregnancy (Day 16 and Day 22). This suggests that,
      similar to the pig, IFN-delta could play an important role in maternal-fetal
      interactions during early pregnancy in the horse.

PMID- 19110042
TI  - Effects of maternal toluene exposure on testosterone levels in fetal rats.
AB  - The goal of our study was to determine if toluene affected the synthesis and
      secretion of testosterone in fetal rats. Dams were exposed to atmospheres that
      contained 0.09 ppm, 0.9 ppm or 9 ppm of toluene for 90 min/day from gestational
      days (GDs) 14.5 to 18.5 via nasal inhalation. Fetal plasma testosterone
      concentrations determined by enzyme immunoassay were significantly reduced on GD
      18.5 after exposure to 0.9 and 9 ppm, but not to 0.09 ppm, of toluene in male,
      but not in female, fetuses. We measured, using real-time PCR methods, mRNA levels
      in fetal testes for several steroidogenic enzymes involved in testosterone
      synthesis and insulin-like 3 (Insl3), a maker of Leydig cell differentiation. The
      mRNA levels of 3beta-hydroxysteroid dehydrogenase (3beta-HSD) were significantly
      reduced after exposure to 0.9-ppm toluene. However, the mRNA levels of cytochrome
      P450 cholesterol side-chain cleavage, cytochrome P450 17alpha-hydroxylase/c17-20
      lyase, 17beta-hydroxysteroid dehydrogenase, and Insl3 were not significantly
      altered by exposure to 0.9-ppm toluene. In addition, immunohistochemical analysis
      showed reduced 3beta-HSD-immunoreactive areas in the interstitial region of fetal
      testes after exposure to 0.9 and 9 ppm, but not 0.09 ppm, toluene. These findings
      indicate that toluene reduced the synthesis and secretion of testosterone in
      fetal testes from rats possibly as a consequence of reduced 3beta-HSD expression.

PMID- 19110043
TI  - ortho-Phthalaldehyde enhances allergen-specific IgE production without allergen
      specific IgG in ovalbumin-sensitized mice.
AB  - ortho-Phthalaldehyde (OPA) is commonly used as a safer and more effective
      chemical disinfectant for use with medical devices in hospitals. However, the
      cases of patients with occupational bronchial asthma or contact dermatitis are
      recently reported among workers in the medical professions who were exposed to
      OPA disinfectant. Mechanism of allergic reaction associated with OPA is poorly
      understood. The purpose of this study is that OPA may act as an immunological
      adjuvant in the allergic reaction accompanied by enhanced specific-IgE production
      in response to allergen challenge in OVA-sensitized mice. OPA induced increase of
      total cell numbers, and reflected infiltration of neutrophils in BAL fluid after
      allergen challenge in sensitized mice, dose-dependently. However, total protein
      concentration in BAL fluid did not change in the all of groups. The OPA induced
      up-regulation of eotaxin and monocyte chemotactic protein-1 mRNAs in the lung as
      well as the increase in OVA-specific IgE in sensitized mice compared with non
      sensitized controlled mice without increase in the level of OVA-specific IgG.
      Cytokines IL-4 and IL-5 mRNA were expressed by allergen (OVA) challenge in both
      lungs collected from OPA-administrated-sensitized and OPA-administrated
      nonsensitized mice. From these data, we concluded that low concentration of OPA
      that enhanced the OVA-induced recruitment of neutrophils to the lung and the
      production of allergen-specific IgE, suggesting that OPA acts as an immunological
      adjuvant.

PMID- 19110044
TI  - Gene profiles of a human alveolar epithelial cell line after in vitro exposure to
      respiratory (non-)sensitizing chemicals: identification of discriminating genetic
      markers and pathway analysis.
AB  - There are currently no accepted biological prediction models for assessing the
      potential of a substance to cause respiratory sensitization. New tests should be
      based on mechanistic understanding and should be preferentially restricted to in
      vitro assays. The major goal of this study was to investigate the alterations in
      gene expression of human alveolar epithelial (A549) cells after exposure to
      respiratory sensitizing and non-respiratory sensitizing chemicals, and to
      identify genes that are able to discriminate between both groups of chemicals.
      A549 cells were exposed during 6, 10, and 24 h to the respiratory sensitizers
      ammonium hexachloroplatinate IV, hexamethylene diisocyanate, and trimellitic
      anhydride, the irritants acrolein and methyl salicylate, and the skin sensitizer
      1-chloro-2,4-dinitrobenzene. Overall changes in gene expression were evaluated
      using Agilent Whole Human Genome 4x44K oligonucleotide arrays. A Fisher linear
      discriminant analysis was used to obtain a ranking of genes that reflects their
      potential to discriminate between respiratory sensitizing and respiratory non
      sensitizing chemicals. Among the 20 most discriminating genes, which were
      categorized into molecular and biological gene ontology (GO) terms, CTLA4 could
      be associated with asthma and/or respiratory sensitization. When categorizing the
      top-1000 genes into biological GO terms, 22 genes were associated with immune
      function. Using a pathway analysis tool to identify possible underlying
      mechanisms of respiratory sensitization, no known canonical signaling pathway was
      observed to be activated in the A549 cell line.

PMID- 19110045
TI  - Hesperidin inhibited acetaldehyde-induced matrix metalloproteinase-9 gene
      expression in human hepatocellular carcinoma cells.
AB  - Previous studies have revealed that acetaldehyde-induced cell invasion and matrix
      metalloproteinase-9 (MMP-9) activation and are directly involved in hepatic
      tumorigenesis and metastasis. Acetaldehyde is an important substance for tumor
      regression. We designed this study to aid in the development of powerful anti
      cancer drugs with specific tumor regression and anti-metastatic potentials.
      Optimal drugs should possess both specific MMP-9 enzyme and gene transcriptional
      activities at the molecular level. Hesperidin, a flavonoid present in fruits and
      vegetables, possess anti-inflammatory and chemopreventive activities. Hesperidin
      suppressed acetaldehyde-induced cell invasion and inhibited the secreted and
      cytosolic MMP-9 forms in HepG2 cells with acetaldehyde. Hesperidin suppressed
      acetaldehyde-induced MMP-9 expression through the inhibition of nuclear factor
      kappaB (NF-kappaB) and AP-1, and suppressed acetaldehyde-stimulated NF-kappaB
      translocation into the nucleus through IkappaB inhibitory signaling pathways.
      Hesperidin also inhibited acetaldehyde-induced AP-1 activity by the inhibitory
      phosphorylation of p38 kinase and c-Jun N-terminal kinase (JNK) signaling
      pathways. Results from our study revealed that hesperidin suppressed both
      acetaldehyde-activated NF-kappaB and activator protein 1 (AP-1) activity by
      IkappaB, JNK, and p38 signaling pathways. This resulted in the reduction of MMP-9
      expression, secretion, and hepatocarcinoma cellular invasion. Our result
      confirmed the therapeutic potential of hesperidin an anti-metastatic and its
      involvement in the acetaldehyde-induced cell invasiveness of hepatocellular
      carcinoma in alcoholic patients.

PMID- 19110046
TI  - A clinically relevant in vitro model for evaluating the effects of aerosolized
      vesicants.
AB  - The chemical warfare vesicant sulfur mustard (HD) is a known toxic agent to the
      human respiratory tract and the major airways are considered to be a primary
      target of HD-induced injury. However, there is no consensus regarding which model
      systems are most appropriate for studying the effects of aerosolized vesicants on
      human airway epithelium. In this study, we evaluated the consequences of exposure
      of differentiated human respiratory epithelial cells in air-liquid interface to
      mechlorethamine (HN2), an HD functional analog. HN2 challenge was administered
      via the apical (air) interface over a wide dose range (20-400 microM) to
      differentiated HBE1 cells. Cultures were observed over 1-48 h for evidence of HN2
      induced morphologic abnormalities as well as for possible cellular cytotoxicity,
      apoptotic changes, and induction of cytokine secretion. HN2 at concentrations of
      > or =200 microM caused disruption and denudation of the airway epithelial
      architecture within 24h of exposure. Moreover, HN2-induced cytotoxic and
      apoptotic changes in HBE1 cells in a dose- and time-dependent fashion. HN2
      challenge also induced secretion of chemokines and proinflammatory cytokines
      including TNF-alpha, IL-1 alpha, IL-1 beta, IL-6, IL-8, RANTES, MCP-1, IP-10, G
      CSF, GM-CSF and IL-15. These observations parallel those described in the lungs
      of HD-exposed victims and underscore the utility and potential applicability of
      this model to future mechanistic studies of vesicant-induced pulmonary injury.

PMID- 19110048
TI  - Practical model description of peripheral neural excitation in cochlear implant
      recipients: 5. refractory recovery and facilitation.
AB  - In this paper the neural response to electrical stimulation with short inter
      pulse intervals was examined. The refractory recovery of the electrically-evoked
      compound action potential (ECAP) was recorded using masker pulses with a wide
      range of currents relative to the probe pulse. The ECAP was recorded in subjects
      implanted with the Nucleus 24 cochlear implant system (three with straight and
      two with Contour electrode arrays), using the Neural Response Telemetry (NRT)
      system. Employing the non-refractory parameters previously obtained in the fourth
      paper of the series and a two-parameter neural refractory recovery function, the
      model was fitted to ECAP recovery data for a case where the masker current was
      high relative to that of the probe and masking assumed to be almost complete. A
      single pair of refractory parameters, fitted at one probe current, allowed the
      model to describe quite well the ECAP recovery functions for different probe
      currents. Facilitatory contributions to the recovery functions, for differing
      current of masker relative to probe, were quantified by comparing experimental
      recovery functions with modeled functions that included only refractory behavior.
      The model should provide the means to improve speech processing algorithms for
      cochlear implants, by allowing the systematic incorporation of additional
      information concerning the neural response to electrical stimulation.

PMID- 19110047
TI  - Stimulus experience modifies auditory neuromagnetic responses in young and older
      listeners.
AB  - Experiencing repeatedly presented auditory stimuli during magnetoencephalographic
      (MEG) recording may affect how the sound is processed in the listener's brain and
      may modify auditory evoked responses over the time course of the experiment.
      Amplitudes of N1 and P2 responses have been proposed as indicators for the
      outcome of training and learning studies. In this context the effect of merely
      sound experience on N1 and P2 responses was studied during two experimental
      sessions on different days with young, middle-aged, and older participants
      passively listening to speech stimuli and a noise sound. N1 and P2 were
      characterized as functionally distinct responses with P2 sources located more
      anterior than N1 in auditory cortices. N1 amplitudes decreased continuously
      during each recording session, but completely recovered between sessions. In
      contrast, P2 amplitudes were fairly constant within a session but increased from
      the first to the second day of MEG recording. Whereas N1 decrease was independent
      of age, the amount of P2 amplitude increase diminished with age. Temporal
      dynamics of N1 and P2 amplitudes were interpreted as reflecting neuroplastic
      changes along different time scales. The long lasting increase in P2 amplitude
      indicates that the auditory P2 response is potentially an important physiological
      correlate of perceptual learning, memory, and training.

PMID- 19110049
TI  - Practical model description of peripheral neural excitation in cochlear implant
      recipients: 4. model development at low pulse rates: general model and
      application to individuals.
AB  - This fourth paper in the series presents the initial development of the model at
      low pulse rates, where refractory behavior is minimal. This is a necessary
      developmental stage that makes possible the subsequent incorporation of temporal
      effects, in the fifth paper. The model comprises a population of neural fibers
      spread along the cochlear duct, with normally distributed thresholds. Each has a
      finite dynamic range, allowing stochastic behavior. The fibers are stimulated by
      a field that is attenuated longitudinally according to a model-based function,
      scaled to fit an individual ECAP (compound action potential) measure of effective
      field attenuation. First, the model parameters were tuned to provide general
      trend matches to: the observed range of maximum comfortable level (MCL); the
      relationship between threshold and MCL; and the relationship between curvature of
      the loudness growth function and MCL. These trend differences between patients
      are explained by differing percentage of neural survival, although additional
      parameters clearly influence individual behavior. Second, the model was fitted to
      three electrodes in each of six subjects implanted with the Nucleus 24 cochlear
      implant system (three with straight and three with Contour electrode arrays).
      Across the subjects, different values were required for the "relative spread", a
      measure of neural fiber dynamic range relative to threshold, which indicated
      differences in neural stochasticity. The consistency of the fittings was assessed
      by comparing model emulations of the ECAP "spread of excitation" (SOE) measure
      with experimental findings.

PMID- 19110050
TI  - Selection of cytotoxicity markers for the screening of new chemical entities in a
      pharmaceutical context: a preliminary study using a multiplexing approach.
AB  - The present study was undertaken to validate a battery of cytotoxicity assays
      performed in a multiplex format to screen pharmaceutical compounds at an early
      stage of drug development. Two experiments were performed on HepG2 cells and the
      parameters were measured in 96-well plates. Biological and technical triplicates
      were performed to evaluate the reproducibility of the assay. In the first
      experiment, HepG2 cells were exposed to tamoxifen, staurosporine, phenobarbital
      and triton X-100 for 2 and 24h. The following nine cytotoxicity parameters were
      analyzed, cell viability, lactate dehydrogenase (LDH), adenosine triphosphate
      (ATP), caspase-3/7, aspartate aminotransferase (AST), glutamate dehydrogenase
      (GLDH), alanine aminotransferase (ALT), alkaline phosphatase (ALP) and alpha
      glutathione-S-transferase (alpha-GST). In the second experiment, HepG2 cells were
      exposed to doxorubicin, t-butyl hydroperoxide, ferrous sulfate and sulfamoxole
      for 2 and 24h. Based on the results of the first experiment, six cytotoxicity
      parameters were selected for further evaluation (cell viability, ATP, LDH,
      caspase, AST and GLDH). ALT (activity always below detection limit), ALP (no
      response to drug treatment) and alpha-GST (too labor intensive and not possible
      to multiplex) were eliminated. The analysis of the data revealed that the
      reproducibility of the assays was accurate according to principal component
      analysis. Our data also clearly indicated that the potential of this battery of
      selected assays measured in a multiplex format not only made it possible to rank
      and select the most promising drug candidates based on their cytotoxic potential,
      but also to gather information that may help to understand some of the toxic
      events occurring in the cells.

PMID- 19110051
TI  - Isoliquiritigenin induces monocytic differentiation of HL-60 cells.
AB  - It has been proven that isoliquiritigenin could inhibit the proliferation of some
      kinds of cancer cell lines and has a strong antioxidative activity. The purpose
      of this study is to investigate whether the antioxidant isoliquiritigenin affects
      the proliferation and redifferentiation in HL-60 cells. The 3-(4,5
      dimethylthiazol-2-yl)-2,5-diphenyltetrazolium (MTT) colorimetric method and
      trypan blue staining were used to measure cell proliferentiation and survival.
      The morphological changes, nitroblue tetrazolium chloride (NBT) reductive
      activity, and the CD11b and CD14 surface antigens were used as the biomarkers of
      redifferentiation of HL-60 cells. The intracellular reactive oxygen species
      (iROS) level was detected by a fluorescent probe, 2,7-dichlorodihydrofluorescein
      diacetate (DCFH-DA). Isoliquiritigenin (ISL) inhibited the cell proliferation and
      decreased the iROS levels in a dose-dependent manner, while the treatment did not
      increase the lethality rate. After 72 h treatment with 10 microg/ml ISL, a
      typical differentiated morphology was observed in HL-60 cells, including the
      decrease of karyoplasmic ratio and the increase of kidney-shape nuclear cells.
      The positive rate (%) of CD11b (26.4+/-3.90 vs 7.70+/-1.04, P<0.01) and CD14
      (20.4+/-2.30 vs 2.63+/-0.133, P<0.01) cells increased significantly. The NBT
      reductive activity increased 2.3-fold as compared to that of the control group.
      As an antioxidant, ISL decreased the iROS formation in a dose-dependent manner.
      All the results indicate that the antioxidant ISL is able to induce the monocytic
      differentiation in leukemia cells. ISL has the potential as a drug to cure
      leukemia with fewer side effects.

PMID- 19110052
TI  - Function of Akt/PKB signaling to cell motility, invasion and the tumor stroma in
      cancer.
AB  - The serine/threonine protein kinase Akt is a major signal transducer of the
      phosphoinositide 3-kinase (PI 3-K) pathway in all cells and tissues and plays a
      pivotal role in the maintenance of cellular processes including cell growth,
      proliferation, survival and metabolism. The frequent aberrant activation of the
      PI 3-K/Akt pathway in human cancer has made it an attractive therapeutic target.
      Numerous studies have provided a comprehensive understanding of the specific
      functions of Akt signaling in cancer cells as well as the surrounding tumor
      microenvironment and this has informed and enabled the development of therapeutic
      drugs to target both PI 3-K and Akt. However, recent studies have provided
      evidence for distinct functions of the three mammalian Akt isoforms, particularly
      with respect to the regulation of cell motility and metastasis of breast cancer.
      Here we discuss the mechanisms by which Akt signaling contributes to invasive
      migration and tumor metastasis, and highlight recent advances in our
      understanding of the contribution of the Akt pathway in the tumor-associated
      stroma.

PMID- 19110054
TI  - Ectopic expression of Ligand-of-Numb protein X promoted TGF-beta induced
      epithelial to mesenchymal transition of proximal tubular epithelial cells.
AB  - Ligand-of-Numb protein X (LNX) was initially characterized as a RING finger type
      E3 ubiquitin ligase that targeted the intrinsic cell fate determinant Numb for
      ubiquitination dependent degradation. However, the physiological function of LNX
      remains largely unknown. In the present study, we demonstrate that ectopic
      expression of LNX in human proximal tubular epithelial cells (HK-2 cells)
      significantly enhanced TGF-beta1 induced epithelial to mesenchymal transition
      (EMT). The EMT-promoting effect of LNX manifested as strong inhibition of E
      cadherin expression, enhanced expression of vimentin, fibronectin or PAI-1, and
      increased cell migration. This function of LNX was shown to be independent of its
      ligase activity because ectopic expression of a mutant form of LNX (C48ALNX) that
      lacks E3 ligase activity had the similar effect as the wild-type LNX.
      Overexpression of E-cadherin could inhibit LNX augmented EMT. This study suggests
      a potential role for LNX in promoting EMT in human proximal tubular epithelial
      cells.

PMID- 19110053
TI  - Plasticity of central autonomic neural circuits in diabetes.
AB  - Regulation of energy metabolism is controlled by the brain, in which key central
      neuronal circuits process a variety of information reflecting nutritional state.
      Special sensory and gastrointestinal afferent neural signals, along with blood
      borne metabolic signals, impinge on parallel central autonomic circuits located
      in the brainstem and hypothalamus to signal changes in metabolic balance.
      Specifically, neural and humoral signals converge on the brainstem vagal system
      and similar signals concentrate in the hypothalamus, with significant overlap
      between both sensory and motor components of each system and extensive cross-talk
      between the systems. This ultimately results in production of coordinated
      regulatory autonomic and neuroendocrine cues to maintain energy homeostasis.
      Therapeutic metabolic adjustments can be accomplished by modulating
      viscerosensory input or autonomic motor output, including altering
      parasympathetic circuitry related to GI, pancreas, and liver regulation. These
      alterations can include pharmacological manipulation, but surgical modification
      of neural signaling should also be considered. In addition, central control of
      visceral function is often compromised by diabetes mellitus, indicating that
      circuit modification should be studied in the context of its effect on neurons in
      the diabetic state. Diabetes has traditionally been handled as a peripheral
      metabolic disease, but the central nervous system plays a crucial role in
      regulating glucose homeostasis. This review focuses on key autonomic brain areas
      associated with management of energy homeostasis and functional changes in these
      areas associated with the development of diabetes.

PMID- 19110055
TI  - Specific and non-specific phagocytosis of ligand-grafted PLGA microspheres by
      macrophages.
AB  - We evaluated the influence of ligand grafting on the rate and intensity of uptake
      of poly(d,l-lactide-co-glycolide) microparticles by alveolar macrophages.
      Microspheres with a mean diameter of 2.5 microm were obtained by spray drying.
      Three ligands (WGA, an RGD containing peptide and mannose-PEG(3)-NH(2)) and a
      cationic molecule (PLL) were covalently grafted on the particle surface using the
      carbodiimide method. Their grafting efficiency was quantified, and WGA grafting
      was characterized by confocal laser scanning microscopy (CLSM) and by atomic
      force microscopy (AFM). The uptake by macrophages of surface-modified
      microspheres was quantified by CLSM. This work showed that the uptake of
      negatively charged ligand-grafted microspheres (-26 to -51 mV) was increased up
      to two to four times according to the ligand compared to ungrafted microspheres (
      81 mV) and displayed saturation as opposed to the cationic PLL-grafted
      microspheres. Moreover, a specific receptor-mediated phagocytosis mechanism was
      suggested based on free ligand, cytochalasin D and +4 degrees C incubation that
      decreased the microparticle uptake. Furthermore, this work clearly showed that
      the relative contribution of specific and non-specific processes to the overall
      uptake varied greatly according to the ligands, and was dependent on the particle
      to-cell ratio. In conclusion, this work showed that ligand grafting can enhance
      the uptake of microparticles, with a variable relative contribution of specific
      and non-specific uptake mechanism.

PMID- 19110056
TI  - In vitro transscleral iontophoresis of high molecular weight neutral compounds.
AB  - The aim of the work was to study in vitro, across porcine and human sclera, the
      effect of transscleral iontophoresis on the permeation of high molecular weight
      neutral dextrans, chosen as models of high molecular weight drugs. Iontophoretic
      (anodal and cathodal) and passive permeation experiments were performed through
      pig sclera using acetaminophen (MW=151Da) and labelled dextrans (MW between
      4.4kDa and 120kDa) as neutral model compounds. Anodal iontophoresis of 120kDa
      dextran was also performed on human sclera. Membrane charge was also determined
      at different pH values. Both human and pig sclera show a net negative charge at
      pH 7.4 and in the presence of current an electroosmotic convective solvent flow
      in the anode-to-cathode direction takes place. During anodal iontophoresis, the
      electroosmotic flow (whose entity resulted approximately 4 microlcm(-2)h(-1)) was
      able to increase 2-6.5 times the transscleral flux of dextrans. Transscleral
      iontophoresis can be useful for enhancing the transport across the sclera of high
      molecular weight compounds, even though neutral. This result suggests a possible
      application of this technique for the non-invasive administration of new biotech
      drugs for the treatment of the posterior segment eye diseases.

PMID- 19110057
TI  - Increased oxidative damage in peripheral blood correlates with severity of
      Parkinson's disease.
AB  - Increased oxidative stress contributes to neuronal dysfunction in Parkinson's
      disease (PD). We investigated whether the pathological changes in PD brains may
      also be present in peripheral tissues. Leukocyte 8-hydroxydeoxyguanosine (8
      OHdG), plasma malondialdehyde (MDA), erythrocyte glutathione peroxidase (GPx) and
      plasma vitamin E (Vit E) were measured for 211 PD patients and 135 healthy
      controls. Leukocyte 8-OHdG and plasma MDA were elevated, whereas erythrocyte GPx
      and plasma Vit E were reduced in PD patients when compared to the controls. After
      adjusting for environmental factors, logistic regression analysis showed that PD
      severity was independently correlated with 8-OHdG and MDA level, and inversely
      correlated with GPx activity and Vit E level. Leucocyte 8-OHdG level was
      continuously increased with advanced PD Hoehn-Yahr stages, while plasma MDA level
      peaked at early disease stages, among PD patients. These results suggest
      increased oxidative damage and decreased anti-oxidant capacity in peripheral
      blood, and a significant correlation between leucocyte 8-OHdG level and disease
      severity in PD.

PMID- 19110058
TI  - MicroRNA regulation of Alzheimer's Amyloid precursor protein expression.
AB  - Gene dosage effects of Amyloid precursor protein (APP) can cause familial AD.
      Recent evidence suggest that microRNA (miRNA) pathways, implicated in gene
      transcriptional control, could be involved in the development of sporadic
      Alzheimer's disease (AD). We therefore investigated whether miRNAs could
      participate in the regulation of APP gene expression. We show that miRNAs
      belonging to the miR-20a family (that is, miR-20a, miR-17-5p and miR-106b) could
      regulate APP expression in vitro and at the endogenous level in neuronal cell
      lines. A tight correlation between these miRNAs and APP was found during brain
      development and in differentiating neurons. We thus identify miRNAs as novel
      endogenous regulators of APP expression, suggesting that variations in miRNA
      expression could contribute to changes in APP expression in the brain during
      development and disease. This possibility is further corroborated by the
      observation that a statistically significant decrease in miR-106b expression was
      found in sporadic AD patients.

PMID- 19110059
TI  - Minocycline restores striatal tyrosine hydroxylase in GDNF heterozygous mice but
      not in methamphetamine-treated mice.
AB  - Inflammation, phospho-p38 MAPK activation, and a reduction in glial cell line
      derived neurotrophic factor (GDNF) occur in Parkinson's disease. Microglial
      activation in the substantia nigra and a tyrosine hydroxylase deficit in the
      striatum of 3-month-old GDNF heterozygous (GDNF(+/-)) mice were previously
      reported and both were exacerbated by a toxic methamphetamine binge. The current
      study assessed the effects of minocycline on these methamphetamine-induced
      effects. Minocycline (45 mg/kg, i.p.x 14 days post-methamphetamine or saline
      injections) reduced microglial activation and phospho-p38 MAPK in the substantia
      nigra of saline-treated GDNF(+/-) mice and in methamphetamine-treated wildtype
      and GDNF(+/-) mice. Although minocycline increased tyrosine hydroxylase
      immunoreactivity in GDNF(+/-) mice, it did not attenuate the methamphetamine
      induced reduction of tyrosine hydroxylase. The results suggest that
      neuroinflammation is deleterious to the dopamine system of GDNF(+/-) mice but is
      not the primary cause of methamphetamine-induced damage to the dopamine system in
      either GDNF(+/-) or wildtype mice.

PMID- 19110060
TI  - LPS response and tolerance in the zebrafish (Danio rerio).
AB  - Zebrafish (Danio rerio) has been used in the present work to study the fish
      response to bacterial lipopolysaccharide (LPS) exposure and LPS tolerance. These
      mechanisms are not completely understood in mammals and, presently, are totally
      unknown in fish. Zebrafish larval survival was assessed following treatment with
      various types of LPS at a variety of concentrations to determine the sensitivity
      of zebrafish to LPS-induced immune activation. In addition, fish pretreated with
      a sublethal concentration of LPS did not die after exposure to a lethal
      concentration of LPS demonstrating, for the first time that LPS tolerance also
      happens in fish. The time interval between pretreatment and secondary exposure as
      well as the type of pretreatment dictated the strength of protection. Since
      zebrafish are in intimate contact with microorganisms, the high resistance of
      fish to LPS suggests that there must be a tight control of the LPS receptor
      cluster in order to avoid an excess of inflammation. One of these components is
      CXCR4, which has previously been shown to regulate the signal transduced by TLR4.
      Treating fish with AMD3100, a specific inhibitor of CXCR4, increased LPS
      treatment associated mortality. Blocking CXCR4 via chemical or genetic inhibition
      resulted in a reversion of LPS tolerance, thus further supporting the negative
      regulatory role of CXCR4 in this inflammatory response. In support of an
      inhibitory role for CXCR4 in the inflammatory cascade, IL-1 transcript levels
      were elevated in both unstimulated and LPS stimulated zebrafish Odysseus (CXCR4
      deficient mutant) larvae.

PMID- 19110062
TI  - EEG-vigilance and BOLD effect during simultaneous EEG/fMRI measurement.
AB  - Different EEG-vigilance stages from full alertness to sleep onset can be
      separated during rest. Also fMRI research recently focused on the resting
      condition and identified several resting state networks. In order to deepen the
      understanding of different levels of global brain function from relaxed
      wakefulness to sleep onset the association between EEG-vigilance stages and BOLD
      signals was analysed. EEG-vigilance stages were attributed to consecutive 3-sec
      EEG-segments by an algorithm using topographic and spectral information. Results
      of the classification were validated by analysing the heart rates during the
      different brain states. Vigilance stages served as regressors for the analysis of
      the simultaneously acquired fMRI data. Additionally resting state networks were
      derived from the fMRI data using independent component analysis (ICA). Also
      vigilance associated brain activity revealed by EEG-based standardized low
      resolution tomography (sLORETA) was compared to the results of the fMRI analysis.
      Results showed increased BOLD signal in the occipital cortex, the anterior
      cingulate cortex, the frontal cortex, the parietal cortices and the temporal
      cortices and decreasing BOLD signals in the thalamus and the frontal cortex for
      declining vigilance stages (A2, A3, B1, B2/B3) in comparison to the high
      vigilance stage A1. Resting state networks revealed a spatial overlap with the
      vigilance stage associated BOLD maps in conjunction analyses. sLORETA showed
      increased neuroelectric alpha activity at the occipital cortex comparable to
      occipital BOLD signal decreases when comparing stage A with stage B. Different
      EEG-vigilance stages during rest are associated with pronounced differences of
      BOLD signals in several brain areas which partly correspond to the resting state
      networks. For cognitive fMRI-research it therefore seems important to pay
      attention to vigilance switches in order to separate vigilance associated BOLD
      signal changes from those specifically related to cognition.

PMID- 19110061
TI  - Functional connectivity of the human amygdala using resting state fMRI.
AB  - The amygdala is composed of structurally and functionally distinct nuclei that
      contribute to the processing of emotion through interactions with other
      subcortical and cortical structures. While these circuits have been studied
      extensively in animals, human neuroimaging investigations of amygdala-based
      networks have typically considered the amygdala as a single structure, which
      likely masks contributions of individual amygdala subdivisions. The present study
      uses resting state functional magnetic resonance imaging (fMRI) to test whether
      distinct functional connectivity patterns, like those observed in animal studies,
      can be detected across three amygdala subdivisions: laterobasal, centromedial,
      and superficial. In a sample of 65 healthy adults, voxelwise regression analyses
      demonstrated positively-predicted ventral and negatively-predicted dorsal
      networks associated with the total amygdala, consistent with previous animal and
      human studies. Investigation of individual amygdala subdivisions revealed
      distinct differences in connectivity patterns within the amygdala and throughout
      the brain. Spontaneous activity in the laterobasal subdivision predicted activity
      in temporal and frontal regions, while activity in the centromedial nuclei
      predicted activity primarily in striatum. Activity in the superficial subdivision
      positively predicted activity throughout the limbic lobe. These findings suggest
      that resting state fMRI can be used to investigate human amygdala networks at a
      greater level of detail than previously appreciated, allowing for the further
      advancement of translational models.

PMID- 19110063
TI  - The hippocampus and prefrontal cortex are differentially involved in serial
      memory retrieval in non-stress and stress conditions.
AB  - We previously showed that 24h after learning, mice significantly remembered the
      first (D1) but not the second (D2) discrimination in a serial spatial task and
      that an acute stress delivered 5min before the test phase reversed this memory
      retrieval pattern. A first experiment evaluated the effects of dorsal hippocampus
      (HPC) or prefrontal cortex (PFC) lesions, these two brain areas being well-known
      for their involvement in serial and spatial memory processes. For this purpose,
      six independent groups of mice were used: non-lesioned (controls), PFC or HPC
      lesioned animals, submitted or not to an acute stress (electric footshocks;
      0.9mA). Results show that (i) non-stressed controls as well as PFC-lesioned mice
      (stressed or not) remembered D1 but not D2; (ii) stressed controls and HPC
      lesioned mice (stressed or not) remembered D2 but not D1; (iii) stress
      significantly increased plasma corticosterone in controls and PFC-lesioned mice,
      but not in HPC-lesioned mice which already showed a significant plasma
      corticosterone increase in non-stressed condition. Since data from this first
      experiment showed that stress inhibited the hippocampal-dependent D1 memory
      retrieval, a second experiment evaluated the behavioral effect of
      intrahippocampal corticosterone injection in non-stressed mice. Results show that
      intrahippocampal corticosterone injection induced a reversal of serial memory
      retrieval pattern similar to that induced by acute stress. Overall, our study
      shows that (i) in non-stress condition, the emergence of D1 is HPC-dependent;
      (ii) in stress condition, the emergence of D2 requires the PFC integrity;
      moreover, intrahippocampal corticosterone injection mimicked the effects of
      stress in the CSD task.

PMID- 19110064
TI  - Effects of water salinity on melatonin levels in plasma and peripheral tissues
      and on melatonin binding sites in European sea bass (Dicentrarchus labrax).
AB  - Sea bass is an euryhaline fish that lives in a wide range of salinities and
      migrates seasonally from lagoons to the open sea. However, to date, the influence
      of water salinity on sea bass melatonin levels has not been reported. Here, we
      evaluated the differences in plasma and tissue melatonin contents and melatonin
      binding sites in sea bass under four different salinity levels: seawater (36 per
      thousand), isotonic water (15 per thousand), brackish water (4 per thousand) and
      freshwater (0 per thousand). The melatonin content was evaluated in plasma, whole
      brain, gills, intestine and kidney, while melatonin binding sites were analyzed
      in different brain regions and in the neural retina. Plasma melatonin levels at
      mid-dark varied, the lowest value occurring in seawater (102 pg/mL), and the
      highest in freshwater (151 pg/mL). In gills and intestine, however, the highest
      melatonin values were found in the seawater group (209 and 627 pg/g tissue,
      respectively). Melatonin binding sites in the brain also varied with salinity,
      with the highest density observed at the lower salinities in the optic tectum,
      cerebellum and hypothalamus (30.3, 13.0, and 8.0 fmol/mg protein, respectively).
      Melatonin binding sites in the retina showed a similar pattern, with the highest
      values being observed in freshwater. Taken together, these results reveal that
      salinity influences melatonin production and modifies the density of binding
      sites, which suggests that this hormone could play a role in timing seasonal
      events in sea bass, including those linked to fish migration between waters of
      different salinities for reproduction and spawning.

PMID- 19110066
TI  - ApRab3, a biosynthetic Rab protein, accumulates on the maturing phagosomes and
      symbiosomes in the tropical sea anemone, Aiptasia pulchella.
AB  - Symbiosome biogenesis and function are central to the endosymbiotic interaction
      between symbiotic dinoflagellates and their host cnidarians. To understand these
      important organelles, we have been conducting studies to identify and
      characterize symbiosome-associated proteins of the Rab family, key regulatory
      components of vesicular trafficking and membrane fusion in eukaryotic cells. Our
      prior studies have implicated three endocytic Rab proteins in the regulation of
      symbiosome biogenesis. Here, we show that ApRab3 is a new member of the Rab3
      subfamily, associating with symbiosomes and accumulating on the maturing
      phagosomes in the A. pulchella digestive cells. ApRab3 is 78% identical to human
      Rab3C, and contains all Rab 3-specific signature motifs. EGFP-ApRab3-labeled
      vesicular structures tended to either align along the cell peripheral, or
      aggregate at one side of the nucleus. ApRab3 specifically co-distributed with the
      TGN marker, WGA, but not other organelle-specific markers tested.
      Immunofluorescence staining with a specific peptide antibody showed similar
      results. Significantly, an expression of a constitutively active mutant caused
      the enlargement and random dispersion of EGFP-ApRab3-decorated compartments in
      PC12 cells. Together, these data suggest that ApRab3 is a new member of the Rab3
      subfamily, participating in the biosynthetic trafficking pathway, and symbiosome
      biogenesis involves an interaction with ApRab3-positive vesicles.

PMID- 19110065
TI  - Carboxylesterase activity, cDNA sequence, and gene expression in malathion
      susceptible and resistant strains of the cotton aphid, Aphis gossypii.
AB  - Levels of insecticide resistance, carboxylesterase activity, carboxylesterase
      expression, and the cDNA sequence of carboxylesterase gene were investigated in
      malathion resistant and susceptible strains of cotton aphids, Aphis gossypii
      (Glover). The resistant strain (MRR) exhibited 80.6-fold resistance to malathion
      compared to the susceptible strain (MSS) in cotton aphids. Five substrates, alpha
      naphthyl acetate (alpha-NA), beta-naphthyl acetate (beta-NA), alpha-naphthyl
      propionate (alpha-NPr), alpha-naphthyl butyrate (alpha-NB), alpha-naphthyl
      caprylate (alpha-NC) and S-methyl thiobutyrate (S-MTB) were used to determine
      carboxylesterase activity in MRR and MSS strains of cotton aphids.
      Carboxylesterase activity was significantly higher in MRR strain than in MSS
      strain, 3.7-fold for alpha-NA, 3.0-fold for beta-NA, 2.0-fold for alpha-NPr, 2.9
      fold for alpha-NB and 1.6-fold for alpha-NC, While for S-MTB, there was nearly no
      difference between the two strains. Two site mutations (K14Q and N354D) with high
      frequency were also found by sequence analysis in the MRR strain, compared with
      the MSS strain. The levels of gene expression for carboxylesterase of both MRR
      and MSS strains were determined by real-time quantitative PCRs. Compared with the
      MSS strain, the relative transcription levels and gene copy numbers of the
      carboxylesterase were 1.99- and 4.42-fold in the MRR strain, respectively. These
      results indicated that the increased expression of the carboxylesterase resulted
      from the increased transcription levels of carboxylesterase mRNA and gene copy
      numbers and combined with the site mutants might play role in cotton aphid
      resistance to malathion.

PMID- 19110067
TI  - Structure and urovirulence characteristics of the fecal Escherichia coli
      population among healthy women.
AB  - The fecal Escherichia coli population structure may influence the occurrence and
      etiology of extraintestinal infection, but is poorly understood. Accordingly,
      fecal E. coli from 39 healthy women (30 putative colonies per subject) were
      characterized for clonal identity, urinary tract infection-associated virulence
      traits, and phylogenetic background. The 120 unique E. coli clones (mean, three
      per sample) were distributed by phylogenetic group as follows: A (33%), D (31%),
      B1 (19%), and B2 (17%). However, 36% of women carried > or =1 clone from group
      B2, and 87% had clones from groups B2 and/or D. Of the B2 clones, 90% were from
      pauciclonal fecal samples (< or =4 clones), compared with 47% and 52% of A and B1
      clones (P=.001 and P=.007, respectively). Group B2 and D clones more often were
      dominant within the source sample than group A and B1 clones (60% vs. 41%:
      P=.05). Dominant clones exhibited higher virulence scores than non-dominant
      clones (mean 4.4 vs. 3.1: P=.015). In multilevel regression models, pauciclonal
      sample, B2, and clonal prevalence significantly predicted virulence score. In
      conclusion, within the intestinal E. coli population, virulence-associated
      traits, clonal prevalence, and low fecal clonal diversity are related. Virulence
      associated traits of group B2/D E. coli may enhance fitness within the gut,
      thereby increasing strains' likelihood of causing extraintestinal infection.

PMID- 19110068
TI  - Adjuvanticity effect of sodium alginate on subcutaneously injected BCG in BALB/c
      mice.
AB  - Bacillus Calmette-Guerin (BCG) is the only available vaccine against
      tuberculosis. The research for an improved vaccine is currently a very active
      field of investigation. In the present study, adjuvanticity effect of sterile
      sodium alginate on subcutaneous BCG vaccination in BALB/c mice was investigated.
      Mice were vaccinated subcutaneously with BCG plus alginate and the immune
      response and protective effect were compared to those of mice vaccinated with BCG
      alone by the same route. Proliferative and delayed-type hypersensitivity
      responses, IFN-gamma, specific anti-mycobacterium total IgG, IgG1 and IgG2a
      production were significantly higher in mice immunized subcutaneously with BCG
      plus alginate in comparison with results of mice immunized with BCG alone.
      Following systemic infection with BCG, mice vaccinated with BCG plus alginate had
      lower mean bacterial count compared to those vaccinated with BCG alone. The
      immune responses induced by subcutaneous administration of BCG plus alginate were
      significantly better than the responses induced by standard BCG vaccination.

PMID- 19110069
TI  - In vitro non-homologous DNA end joining assays--the 20th anniversary.
AB  - DNA double-strand breaks (DSBs) are the most serious forms of DNA damage in
      cells. Unrepaired or misrepaired DSBs account for some of the genetic
      instabilities that lead to mutations or cell death, and consequently, to cancer
      predisposition. In human cells non-homologous DNA end joining (NHEJ) is the main
      repair mechanism of these breaks. Systems for DNA end joining study have been
      developing during the last 20 years. New assays have some advantages over earlier
      in vitro DSBs repair assays because they are less time-consuming, allow the use
      of clinical material and examination of the joining DNA ends produced
      physiologically in mammalian cells. Proteins involved in NHEJ repair pathway can
      serve as biomarkers or molecular targets for anticancer drugs. Results of studies
      on NHEJ in cancer could help to select potent repair inhibitors that may
      selectively sensitize tumor cells to ionizing radiation (IR) and chemotherapy.
      Here, we review the principles and practice of in vitro NHEJ assays and provide
      some insights into the future prospects of this assay in cancer diagnosis and
      treatment.

PMID- 19110071
TI  - Methotrexate-induced cytotoxicity and genotoxicity in germ cells of mice:
      intervention of folic and folinic acid.
AB  - Methotrexate (MTX) is an anti-metabolite widely used in the treatment of
      neoplastic disorders, rheumatoid arthritis and psoriasis. The basis for its
      therapeutic efficacy is the inhibition of dihydrofolate reductase (DHFR), a key
      enzyme in the folic acid (FA) metabolism. FA is a water-soluble vitamin which is
      involved in the synthesis of purines and pyrimidines, the essential precursors of
      DNA. Folinic acid (FNA) is the reduced form of FA that circumvents the inhibition
      of DHFR. Folate supplementation during MTX therapy for psoriasis and inflammatory
      arthritis reduces both toxicity and side effects without compromising the
      efficacy. Further, FNA supplementation reduces the common side effects of MTX in
      the treatment of juvenile idiopathic arthritis. FA and FNA are reported to have
      protective effects on MTX-induced genotoxicity in the somatic cells; however
      their protective effects on the germ cells have not been much explored.
      Previously, we evaluated the cytotoxic and genotoxic effects of MTX in the germ
      cells of mice. In the present study, we have intervened FA and FNA for the
      protection of germ cell toxicity induced by MTX in male swiss mice. The animals
      were pre-treated with FA at the doses of 50, 100 and 200 microg/kg for 4
      consecutive days per week and on day five; MTX was administered at the dose of
      20mg/kg once. FNA was administered at the doses of 2.5, 5 and 10 mg/kg, 6 h (h)
      after single administration of MTX at the dose of 20 mg/kg. The dosing regimen
      was continued up to 10 weeks. The germ cell toxicity was evaluated using testes
      weight (wt), sperm count, sperm head morphology, sperm comet assay, histology,
      TUNEL and halo assay in testis. The results clearly demonstrate that prior
      administration of FA and post-treatment with FNA reduces the germ cell toxicity
      induced by MTX as evident from the decreased sperm head abnormalities,
      seminiferous tubule damage, sperm DNA damage, TUNEL positive cells and increased
      sperm counts. In the present study, we report that FA and FNA ameliorate the germ
      cell toxicity of MTX in mice.

PMID- 19110070
TI  - Fibroblast growth factor-2 modulates melanoma adhesion and migration through a
      syndecan-4-dependent mechanism.
AB  - Fibroblast growth factor-2 (FGF-2), the most abundant growth factor produced by
      melanoma cells but not by normal melanocytes, is an important regulator of cell
      proliferation, migration and differentiation. In this study we show that M5 human
      metastatic melanoma cells' ability to migrate is significantly enhanced by
      exogenously added FGF-2 while, neutralization of endogenous FGF-2 stimulates
      their adhesion. Previously, we have demonstrated that FGF-2 distinctly modulates
      the synthesis of individual glycosaminoglycans/proteoglycans (GAGs/PGs)
      subclasses, changing both their amounts and distribution in M5 cells. Here,
      treatment with FGF-2 strongly reduces the expression levels of the heparan
      sulfate-containing proteoglycan, syndecan-4. Syndecan-4 is a focal adhesion
      component in a range of cell types, adherent to several different matrix
      molecules, including fibronectin (FN). The reduction in syndecan-4 expression by
      utilizing specific siRNA discriminately increased melanoma cell motility and
      decreased their attachment on FN, demonstrating a regulatory role of syndecan-4
      on these cell functions. Syndecan-4 has previously been demonstrated to regulate
      focal adhesion kinase (FAK) phosphorylation. In this study FGF-2 was shown to
      downregulate FAK Y397-phosphorylation during FN-mediated M5 cell adhesion,
      promoting their migration. The observed decrease in FAK Y397 activation was
      correlated to syndecan-4 expression levels. Thus, a balance in syndecan-4
      expression perpetrated by FGF-2 may be required for optimal M5 cell migration.
      These results suggest that essential in melanoma progression FGF-2, specifically
      regulates melanoma cell ability to migrate through a syndecan-4-dependent
      mechanism.

PMID- 19110072
TI  - Obstacles to mental health care in pediatric epilepsy: insight from parents.
AB  - This exploratory study compared the responses of 20 Caucasian and 20 Hispanic
      mothers of children with epilepsy about possible obstacles to mental health care
      (MHC) for their children before and after they read a brochure on the
      neurobehavioral comorbidities of epilepsy. The intervention significantly
      increased the mothers' knowledge of the behavior and cognitive comorbidities of
      pediatric epilepsy and their treatment. Baseline differences in the attitude
      toward MHC and the stigma of epilepsy between Hispanic and Caucasian mothers were
      no longer apparent after the intervention. Irrespective of ethnicity, the mothers
      also became significantly more aware that their children did not want to have
      epilepsy-related behavior and learning difficulties. Efficient use of time spent
      in doctors' waiting rooms to educate parents about the neurobehavioral
      comorbidities of epilepsy can address the lack-of-knowledge barrier to MHC.
      However, the study's findings suggested a need to determine if there are specific
      obstacles to MHC in pediatric epilepsy.

PMID- 19110073
TI  - Insidious weight gain in prepubertal seized rats treated with an atypical
      neuroleptic: the role of food consumption, fluid consumption, and spontaneous
      ambulatory activity.
AB  - Extreme obesity slowly develops in female rats over the months following seizures
      induced by a single systemic injection of lithium and pilocarpine if the
      resulting limbic seizures are treated with the atypical neuroleptic acepromazine
      (but not with ketamine). To discern the contributions from food consumption,
      water consumption, and (daytime and nighttime) activity to this weight gain,
      these behaviors were monitored for 4 months, about 2 months after seizure
      induction. The results indicated that the rats that underwent the obesity
      procedure exhibited 50% heavier body weights and consumed 42% more food than the
      reference group, which included rats that had been induced to seize but treated
      with ketamine. There were no statistically significant differences between groups
      with respect to either water consumption or (daytime or nighttime) activity.
      Factor analyses of data for individual rats verified the dissociation between
      activity and weight gain for the obese rats. The results suggest that the
      progressive weight gains are centrally mediated and are not secondary to
      diminished activity or altered fluid consumption.

PMID- 19110074
TI  - Does the lunar phase have an effect on sudden unexpected death in epilepsy?
AB  - The incidence of sudden unexpected death in epilepsy (SUDEP) in our epilepsy unit
      over an 8-year period was analyzed to determine a possible association between
      phase of the moon and SUDEP. Analysis revealed that the number of SUDEPs was
      highest in full moon (70%), followed by waxing moon (20%) and new moon (10%). No
      SUDEPs occurred during the waning cycle. These preliminary findings suggest that
      the full moon appears to correlate with SUDEP.

PMID- 19110075
TI  - In vitro and in vivo anti-inflammatory effects of andrographolide.
AB  - Andrographolide - the major active principle isolated from the plant Andrographis
      paniculata, has been shown to possess a strong anti-inflammatory activity. The
      possibility that the drug may affect asthmatic inflammation, through inhibition
      of the relevant inflammatory cytokines, has not been explored. The purpose of
      this study was, firstly, to investigate the ability of andrographolide to inhibit
      the release of inflammatory cytokines in vitro in a model of non-specific
      inflammation and subsequently to determine whether such effect can also be
      exerted in vivo in allergic lung inflammation. LPS-induced TNF-alpha and GM-CSF
      release from mouse peritoneal macrophages was inhibited by andrographolide in a
      concentration-dependent manner. The concentration of the drug producing 50%
      inhibition was 0.6 microM for TNF-alpha and 3.3 microM for GM-CSF. The maximal
      inhibition achieved (at 50 microM) was 77% and 94%, respectively, for the two
      cytokines. The drug was as efficacious as dexamethasone, but about 8-12 times
      less potent. The drug also suppressed LPS-induced expression of mRNA for the two
      cytokines, suggesting that this effect may contribute to the mechanism underlying
      its anti-inflammatory effects. In the in vivo study, intra-peritoneal treatment
      of ovalbumin-immunized and nasally-challenged mice with andrographolide
      significantly inhibited the elevation of bronchoalveolar fluid (BAF) levels of
      TNF-alpha and GM-CSF in a dose-dependent manner, with 30 mg/kg producing an
      inhibition of 92% and 65% of the cytokines, respectively) and almost completely
      abolishing the accumulation of lymphocytes and eosinophils. These results provide
      evidence that andrographolide is an effective anti-inflammatory drug that is
      active in vitro and in vivo, and affects both non-specific as well as
      antigen/antibody-dependent lung inflammation. Thus, andrographolide has the
      potential to be used in a variety of inflammatory conditions, including allergic
      lung inflammation.

PMID- 19110077
TI  - Altered chain-length and glycosylation modify the pharmacokinetics of human serum
      albumin.
AB  - Human serum albumin with modified plasma half-life will be useful for clinical
      purposes. Therefore, the pharmacokinetics of three of each of the following types
      of genetic variants, and of their corresponding normal albumin, were examined in
      mice: N-terminally elongated, C-terminally truncated and glycosylated albumins.
      Isoforms differing from the normal protein by three or more amino acids,
      especially two of the truncated forms, had shorter half-lives. The effect of
      glycosylation depended on the position of attachment: in domain II it increased
      half-life, whereas in domain I and III it had no significant effect. Liver,
      kidney and spleen uptake clearances were also modified. The pronounced changes in
      half-life of the two truncated variants and the glycosylated isoform could be
      explained, at least partly, by large changes in organ uptakes; in the remaining
      six cases, different effects were registered. Such information should be useful
      when designing therapeutical albumin products for, e.g., drug delivery systems.
      In addition to various types of cell endocytosis, leading to intracellular
      destruction or recycling of the proteins, the metabolism of the alloalbumins
      could be affected by plasma enzymes. No correlation was found between mutation
      induced changes in the pharmacokinetic parameters and changes in alpha-helical
      content or changes in heat stability as represented by DeltaH(v).

PMID- 19110076
TI  - Maturational changes in pontine and medullary alpha-adrenoceptor influences on
      respiratory rhythm generation in neonatal rats.
AB  - We examined developmental changes in alpha-adrenoceptor influences and descending
      pontine inputs on the medullary respiratory network in the neonatal rat in vitro
      brainstem-spinal cord preparation. Using a split bath preparation to isolate the
      pons from the medulla, antagonists for alpha1 and alpha2 adrenoreceptors were
      applied to only the medulla at postnatal days 0, 2 and 4, before and after
      transection of the pons. Blocking alpha1 and alpha2 receptors in the medulla in
      the absence of a pons reduced burst frequency at all ages with a more pronounced
      effect in younger animals. At all ages the presence of a pons diminished the
      effect of blocking alpha2 receptors in the medulla and eliminated the effect of
      blocking alpha1 receptors. These results indicate that there is a tonic release
      of catecholamines within the medulla that is under influence from the pons.
      Additionally, transection experiments indicated that during development, the net
      influence of the pons changed from one of excitation to one of inhibition.

PMID- 19110078
TI  - Structure and stability of a thioredoxin reductase from Sulfolobus solfataricus:
      a thermostable protein with two functions.
AB  - Recent investigations have demonstrated that disulfide bridges may play a crucial
      role in the stabilization of proteins in hyperthermophilic organisms. A major
      role in the process of disulfide formation is played by ubiquitous proteins
      belonging to the thioredoxin superfamily, which includes thioredoxins (Trx),
      thioredoxin reductases (TrxR), and disulfide oxidases/isomerases (PDO/PDI). Here
      we report a characterization of the structure and stability of the TrxR
      (SsTrxRB3) isolated from the archaeon Sulfolobus solfataricus. This protein is
      particularly interesting since it is able to process different substrates (Trxs
      and PDO) and it is endowed with an additional NADH oxidase activity. The crystal
      structure of the wild-type enzyme, of its complex with NADP and of the C147A
      mutant provides interesting clues on the enzyme function. In contrast to what is
      observed for class II TrxRs, in the structure of the oxidized enzyme, the FAD
      binding site is occupied by a partially disordered NAD molecule. In the active
      site of the C147A mutant, which exhibits a marginal NADH oxidase activity, the
      FAD is canonically bound to the enzyme. Molecular modeling indicates that a FAD
      molecule can be accommodated in the site of the reduced SsTrxRB3. Depending on
      the oxidation state, SsTrxRB3 can bind a different cofactor in its active site.
      This peculiar feature has been related to its dual activity. Denaturation
      experiments followed by circular dichroism indicate that electrostatic
      interactions play an important role in the stabilization of this thermostable
      protein. The analysis of the enzyme 3D-structure has also provided insights into
      the bases of SsTrxRB3 stability.

PMID- 19110079
TI  - New oxidase from Bjerkandera arthroconidial anamorph that oxidizes both phenolic
      and nonphenolic benzyl alcohols.
AB  - A new flavooxidase is described from a Bjerkandera arthroconidial anamorph. Its
      physicochemical characteristics, a monomeric enzyme containing non-covalently
      bound flavin adenine dinucleotide (FAD), and several catalytic properties, such
      as oxidation of aromatic and polyunsaturated aliphatic primary alcohols, are
      similar to those of Pleurotus eryngii aryl-alcohol oxidase (AAO). However, it
      also efficiently oxidizes phenolic benzyl and cinnamyl alcohols that are typical
      substrates of vanillyl-alcohol oxidase (VAO), a flavooxidase from a different
      family, characterized by its multimeric nature and presence of covalently-bound
      FAD. The enzyme also differs from P. eryngii AAO by having extremely high
      efficiency oxidizing chlorinated benzyl alcohols (1000-1500 s(-1) mM(-1)), a
      feature related to the different alcohol metabolites secreted by the Pleurotus
      and Bjerkandera species including chloroaromatics, and higher activity on
      aromatic aldehydes. What is even more intriguing is the fact that, the new
      oxidase is optimally active at pH 6.0 on both p-anisyl and vanillyl alcohols,
      suggesting a mechanism for phenolic benzyl alcohol oxidation that is different
      from that described in VAO, which proceeds via the substrate phenolate anion
      formed at basic pH. Based on the above properties, and its ADP-binding motif,
      partially detected after N-terminus sequencing, the new enzyme is classified as a
      member of the GMC (glucose-methanol-choline oxidase) oxidoreductase family
      oxidizing both AAO and VAO substrates.

PMID- 19110080
TI  - First case of deletion of the faciogenital dysplasia 1 (FGD1) gene in a patient
      with Aarskog-Scott syndrome.
AB  - Mutations within the faciogenital dysplasia 1 (FGD1) gene in individuals with
      clinical features of Aarskog-Scott syndrome (AAS) include missense mutations and
      insertions and deletions that result in frameshifts and premature terminations.
      Whole gene deletion and duplication represent other mutational possibilities not
      yet reported for FGD1 but known to exist for other genes such as MECP2. We report
      the first case of a boy with clinical features of AAS with deletion of FGD1 gene
      identified using an oligonucleotide-based X chromosome-specific microarray after
      attempts to generate amplicons for all of the FGD1 coding exons failed and BAC
      microarray analysis showed no abnormality.

PMID- 19110082
TI  - The influence of boundary conditions and loading mode on high-resolution finite
      element-computed trabecular tissue properties.
AB  - A widely used technique for determining the material properties of trabecular
      tissue is to perform combined experimental and computational testing of
      trabecular structures in order to calibrate effective tissue properties. To
      better understand the nature of such properties, we tested n=25 cores of human
      vertebral trabecular bone under two different boundary conditions (endcap and
      PMMA embedding) and loading modes (compression and torsion). High-resolution (20
      microm) finite element models that explicitly modeled the different experimental
      conditions were constructed and sensitivity studies were performed to quantify
      errors arising from uncertainties between model and experiment. Mean (+/-S.D.)
      effective tissue modulus for the four groups ranged from 9.6+/-1.9 to 11.5+/-3.5
      GPa, and the overall mean was 10.3+/-2.4 GPa. For the endcap tests, mean values
      were the same regardless of loading mode, suggesting that the effective tissue
      modulus is representative of true material behavior. However, on a specimen
      specific basis, the various repeated measures of effective tissue modulus were
      only moderately correlated with each other (R2=27% to 81%), indicating that the
      individual measures can be subject to appreciable random errors. The sensitivity
      studies on the endcap tests indicated that models using lower resolution (40
      microm element size) and roller-type platens boundary conditions overestimated
      effective tissue modulus by 42% on average, although preliminary tests with
      higher-density femoral neck bone indicated less sensitivity to modeling issues.
      We conclude that effective tissue properties derived from micro-finite element
      models do have biomechanical significance if measured correctly, although
      individual measures of tissue properties may have poor precision.

PMID- 19110083
TI  - Introduction. Review of major recent findings supporting treatments to control
      advanced plaques of atherosclerosis.

PMID- 19110081
TI  - Evolution of organelle-associated protein profiling.
AB  - Identification of the protein constituents of cell organelles forms the basis for
      studies to define the roles of specific proteins in organelle structure and
      functions. Over the past decade, the use of mass spectrometry-based proteomics
      has dissected various organelles and allowed the association of many novel
      proteins with particular organelles. This review chronicles the evolution of
      organelle proteomics technology, and discusses how many limitations, such as
      organelle heterogeneity and purity, can be avoided with recently developed
      quantitative profiling approaches. Although many challenges remain, quantitative
      profiling of organelles holds the promise to begin to address the complex and
      dynamic shuttling of proteins among organelles that will be critical for
      application of this advanced technology to disease-based changes in organelle
      function.

PMID- 19110084
TI  - Diagnosis of atherosclerosis by imaging.
AB  - New and experimental imaging techniques are being developed that will permit
      better visualization and compositional characterization of atheromatous plaques.
      This review provides discussion of techniques that are currently used in clinical
      practice, as well as techniques that are investigational only, including coronary
      angiography, intravascular ultrasound, computed tomography, magnetic resonance
      imaging, positron emission tomography, and single-photon emission computed
      tomography. Types of atheromatous plaque are reviewed, and the value of examining
      vascular calcification in risk assessment is discussed. Experimental use of these
      imaging techniques in animal models and in clinical studies will enhance our
      understanding of the development of plaque and will determine whether these
      techniques would be useful and practical for predicting disease course. Early
      detection and identification of the type of plaque that is present may generate
      novel opportunities for primary prevention through changes in lifestyle or even
      through drug therapy, especially in patients at high cardiovascular risk.

PMID- 19110085
TI  - "Sick fat," metabolic disease, and atherosclerosis.
AB  - Atherosclerotic coronary heart disease (CHD) is the most common cause of
      morbidity and mortality among men and women in developed nations. The obesity
      epidemic contributes to the increasing prevalence of high blood sugar (as may be
      found in patients with diabetes mellitus and metabolic syndrome), high blood
      pressure, and dyslipidemia--all CHD risk factors. Metabolic syndrome describes
      the common clinical finding wherein component CHD risk factors cluster within a
      single patient, but this term does not identify any unified pathophysiologic
      process. However, a component of the metabolic syndrome is abdominal obesity,
      which does reflect an anatomic manifestation of a "common-soil" pathophysiologic
      process that promotes the onset of CHD risk factors, and thus increases CHD risk.
      Adiposopathy ("sick fat") is anatomically characterized by visceral adiposity and
      adipocyte hypertrophy; it is manifested physiologically by a net increase in
      release of free fatty acids and by pathogenic adipose tissue metabolic/immune
      responses that promote metabolic disease and increase CHD risk. Understanding the
      relation of adiposopathy to CHD risk factors and recognizing the importance of
      treating both the "cause and effect" of metabolic diseases are critical toward a
      comprehensive approach in reducing CHD risk. Regarding the "cause," clinicians
      and their patients should be diligent regarding appropriate nutritional and
      lifestyle interventions that may favorably affect health. Regarding the "effect,"
      clinicians and their patients should be equally diligent toward appropriate
      pharmaceutical interventions that reduce CHD risk factors when nutritional and
      lifestyle interventions do not sufficiently achieve desired metabolic treatment
      goals.

PMID- 19110086
TI  - The pathology of atherosclerosis: plaque development and plaque responses to
      medical treatment.
AB  - Atherosclerosis develops over the course of 50 years, beginning in the early
      teenage years. The causes of this process appear to be lipid retention,
      oxidation, and modification, which provoke chronic inflammation at susceptible
      sites in the walls of all major conduit arteries. Initial fatty streaks evolve
      into fibrous plaques, some of which develop into forms that are vulnerable to
      rupture, causing thrombosis or stenosis. Erosion of the surfaces of some plaques
      and rupture of a plaque's calcific nodule into the artery lumen also may trigger
      thrombosis. The process of plaque development is the same regardless of
      race/ethnicity, sex, or geographic location, apparently worldwide. However, the
      rate of development is faster in patients with risk factors such as hypertension,
      tobacco smoking, diabetes mellitus, obesity, and genetic predisposition. Clinical
      trial data demonstrate that treatment with 3-hydroxy-3-methylglutaryl coenzyme A
      reductase inhibitors (statins) favorably alters plaque size, cellular
      composition, chemical composition, and biological activities centered on
      inflammation and cholesterol metabolism, as well as the risk of clinical events
      due to atherosclerosis. Even with advanced atherosclerosis, statins begin to
      improve clinical risk within 4 months. During long-term follow-up in clinical
      trials for up to 11 years with or without further treatment, clinical benefit
      remains significant, indicating the durability of treatment-induced changes in
      the development of plaque. Thus, atherosclerosis, a disease heretofore viewed as
      inevitably progressive, can be treated to significantly alter arterial lesions
      and reduce their clinical consequences.

PMID- 19110087
TI  - Prevention and treatment of atherosclerosis: a practitioner's guide for 2008.
AB  - Atherosclerosis causes nearly 75% of cardiovascular-related deaths and is found
      in 80% to 90% of adults >/=30 years old in the United States. Successful
      treatment minimizes lifetime chances of cardiovascular events, morbidity, and
      mortality. Risk factors for atherosclerosis should be monitored, beginning in
      childhood, even in asymptomatic patients. Modifiable factors (e.g., blood
      pressure, smoking, serum lipids) and nonmodifiable factors (e.g., age, family
      history) are important in the overall assessment. Clinicians and patients can
      partner to produce an individualized treatment plan by choosing from a variety of
      standard approaches. In some patients, improved dietary choices, increased
      exercise, and smoking cessation will reduce risk to an acceptable degree. To
      lower risk further, lipid-lowering pharmacotherapy and antihypertensive
      medication may be combined with these lifestyle improvements. For most of these
      patients, reducing low-density lipoprotein cholesterol is the most important
      lipid-lowering goal, and it is best achieved with a 3-hydroxy-3-methylglutaryl
      coenzyme A reductase inhibitor (statin). Some patients may benefit from
      adjunctive therapies that have proven effects (e.g., niacin, fibrates, plant
      stanols/sterols, omega-3 fatty acids). Antihypertensive regimens may involve
      stepwise adjustments of multiple medications. Good clinical judgment and
      communication of expectations and goals are critical for effective management of
      atherosclerosis.

PMID- 19110088
TI  - Hypercholesterolemia treatment patterns and low-density lipoprotein cholesterol
      monitoring in patients with a diagnosis of atherosclerosis in clinical practice.
AB  - Little is known about the lipid profiles and associated treatment patterns of
      patients in whom atherosclerosis is diagnosed. This investigation assessed and
      described the low-density lipoprotein (LDL) cholesterol levels and treatment
      patterns for hypercholesterolemia in patients with atherosclerosis who were
      treated in routine clinical practice. This retrospective database study used a
      random sample (1 million patients) from a national outpatient electronic medical
      record database (GE Medical Systems, Milwaukee, WI) and included patients with a
      diagnostic code for atherosclerosis (International Classification of Diseases
      [ICD]-9 code of 440.xx or 414.x or 437.x) between January 2004 and March 2006.
      Use of hypercholesterolemia medications at the time ICD codes for atherosclerosis
      were recorded and thereafter was documented. Patient demographics, comorbid
      conditions, baseline LDL cholesterol (closest value within 6 months of the
      diagnosis date), and follow-up LDL cholesterol (after diagnosis) were also
      documented. A total of 10,637 eligible patients had an ICD diagnostic code for
      atherosclerosis. Most patients (61.3%) were not taking any dyslipidemia
      medication at the time of and after atherosclerosis diagnosis. A total of 3% were
      prescribed therapy with a 3-hydroxy-3-methylglutaryl coenzyme A reductase
      inhibitor (statin) before the time of atherosclerosis diagnosis, and 25% were
      prescribed a statin after diagnosis. Approximately 62% of patients with
      atherosclerosis did not have a baseline LDL cholesterol estimate. Of patients
      with LDL cholesterol recorded at diagnosis (n = 4,067), 24% had LDL cholesterol >
      or = 130 mg/dL (1 mg/dL = 0.02586 mmol/L), 53% had LDL cholesterol > or = 100
      mg/dL, and 87% had LDL cholesterol > or = 70 mg/dL. Among patients with LDL
      cholesterol > or = 100 mg/dL at diagnosis, 57% were not prescribed statin
      treatment after diagnosis. Of those with baseline and postdiagnosis LDL
      cholesterol values (n = 1,395), 49% had baseline LDL cholesterol > or = 100
      mg/dL. Among patients on statin or any other hypercholesterolemia therapy after
      diagnosis who had baseline and follow-up LDL cholesterol values (n = 682), 87%
      had baseline LDL cholesterol > or = 70 mg/dL and 51% had baseline LDL cholesterol
      > or = 100 mg/dL, whereas 82% had postdiagnosis LDL cholesterol > or = 70 mg/dL
      and 43% had postdiagnosis LDL cholesterol > or = 100 mg/dL. The results from this
      study, which was conducted in a routine clinical practice setting, indicate the
      opportunities and the need for better monitoring and management of lipid levels
      in patients with atherosclerosis.

PMID- 19110089
TI  - Clinical management of atherosclerosis: a checklist.
AB  - This article provides a checklist designed to aid the busy clinician in
      organizing and implementing an effective course of atherosclerosis evaluation and
      treatment, and a compendium highlighting a selection of useful guidelines for the
      general practitioner.

PMID- 19110090
TI  - Electrochemiluminescence from Ru(bpy)(3)2+ immobilized in poly(3,4
      ethylenedioxythiophene)/poly(styrenesulfonate)-poly(vinyl alcohol) composite
      films.
AB  - Electrochemical behavior and electrogenerated chemiluminescence (ECL) of
      tris(2,2'-bipyridyl)ruthenium(II) (Ru(bpy)(3)(2+)) immobilized in poly(3,4
      ethylenedioxythiophene)/poly(styrenesulfonate)-poly(vinyl alcohol) (PEDOT/PSS
      PVA) composite films via ion-exchange have been investigated with tripropylamine
      (TPA) as the co-reactant at a glassy carbon electrode. The immobilized
      Ru(bpy)(3)(2+) performed a surface-controlled electrode reaction. The
      Ru(bpy)(3)(2+) modified electrode showed a fast ECL response to TPA, and was used
      for the ECL detection of TPA with high sensitivity. The ECL intensity was
      linearly related to concentrations of TPA over the range from 0.50 micromol L(-1)
      to 0.80 mmol L(-1), and the detection limit was 0.10 micromol L(-1) (S/N=3). The
      as-prepared electrode exhibited good precision and long-term stability for TPA
      determination.

PMID- 19110091
TI  - Analytical methods for determination of mycotoxins: a review.
AB  - Mycotoxins are small (MW approximately 700), toxic chemical products formed as
      secondary metabolites by a few fungal species that readily colonise crops and
      contaminate them with toxins in the field or after harvest. Ochratoxins and
      Aflatoxins are mycotoxins of major significance and hence there has been
      significant research on broad range of analytical and detection techniques that
      could be useful and practical. Due to the variety of structures of these toxins,
      it is impossible to use one standard technique for analysis and/or detection.
      Practical requirements for high-sensitivity analysis and the need for a
      specialist laboratory setting create challenges for routine analysis. Several
      existing analytical techniques, which offer flexible and broad-based methods of
      analysis and in some cases detection, have been discussed in this manuscript.
      There are a number of methods used, of which many are lab-based, but to our
      knowledge there seems to be no single technique that stands out above the rest,
      although analytical liquid chromatography, commonly linked with mass spectroscopy
      is likely to be popular. This review manuscript discusses (a) sample pre
      treatment methods such as liquid-liquid extraction (LLE), supercritical fluid
      extraction (SFE), solid phase extraction (SPE), (b) separation methods such as
      (TLC), high performance liquid chromatography (HPLC), gas chromatography (GC),
      and capillary electrophoresis (CE) and (c) others such as ELISA. Further currents
      trends, advantages and disadvantages and future prospects of these methods have
      been discussed.

PMID- 19110092
TI  - A review on speciation of iodine-129 in the environmental and biological samples.
AB  - As a long-lived beta-emitting radioisotope of iodine, (129)I is produced both
      naturally and as a result of human nuclear activities. At present time, the main
      part of (129)I in the environment originates from the human nuclear activity,
      especially the releases from the spent nuclear fuel reprocessing plants, the
      (129)I/(127)I ratios have being reached to values of 10(-10) to 10(-4) in the
      environment from 10(-12) in the pre-nuclear era. In this article, we review the
      occurrence, sources, inventory, and concentration level of (129)I in environment
      and the method for speciation analysis of (129)I in the environment. Measurement
      techniques for the determination of (129)I are presented and compared. An
      overview of applications of (129)I speciation in various scientific disciplines
      such as radiation protection, waste depository, and environmental sciences is
      given. In addition, the bioavailability and radiation toxicity (dose to thyroid)
      of (129)I are discussed.

PMID- 19110093
TI  - Ultrasensitive detection of TNT in soil, water, using enhanced electrogenerated
      chemiluminescence.
AB  - The ultrasensitive detection of 2,4,6-trinitrotoluene (TNT) was accomplished on
      the basis of sandwich-type TNT immunoassay combined with electrogenerated
      chemiluminescence (ECL) technology. Biotinylated anti-TNT species were attached
      to the surface of 1-microm diameter streptavidin-coated magnetic beads (MB) and
      10-microm diameter avidin-coated polystyrene microspheres/beads (PSB) pre-loaded
      with ECL labels ( approximately 7 billion hydrophobic ruthenium(II) tris(2,2'
      bipyridine) (Ru(II)) molecules per bead) to form anti-TNT<-->MB and anti-TNT<-
      >PSB(Ru(II)) conjugates, respectively. Sandwich-type PSB(Ru(II))<-->anti
      TNT<TNT>anti-TNT<-->MB aggregates were formed when PSB(Ru(II))<-->anti-TNT was
      mixed with anti-TNT<-->MB conjugates in the presence of analyte TNT and 2.0%
      bovine serum albumin blocking agent. The newly formed aggregates were
      magnetically separated from the aqueous reaction media and dissolved in
      acetonitrile containing 0.10 M tri-n-propylamine ECL coreactant-0.055 M
      trifluoroacetic acid-0.10 M tetrabutylammonium tetrafluoroborate electrolyte. ECL
      as well as cyclic voltammetric measurements were carried out with a potential
      scan from 0 to 2.8 V vs Ag/Ag(+), and the integrated ECL intensity was found to
      be linearly proportional to the analyte TNT concentration over the range of 0.10
      1000 ppt (pg mL(-1)). The limit of detection (<or=0.10+/-0.01 ppb) is about 600x
      lower as compared with the most sensitive TNT detection method in the literature,
      and the absolute detection limit in mass ( approximately 0.1 pg) is only
      approximately 0.5% of that from mass spectroscopy. The approach coupled with the
      standard addition method was applied to measure the TNT contaminations in soil
      and creek water samples collected from a military training base.

PMID- 19110094
TI  - New and rapid analytical procedure for water content determination: microwave
      accelerated Dean-Stark.
AB  - Development of new procedures in analytical chemistry is currently increasingly
      focussed on reducing the time, cost and energy to carry out routine analyses. The
      conventional Dean-Stark (CDS) distillation to determine the water content is one
      of the most commonly used analytical methods and uses large amounts of solvent
      and energy. A new microwave accelerated Dean-Stark (MADS) distillation is
      presented as an alternative procedure. Microwaves were applied to a mixture of
      toluene, Weflon stir bar and olives, and the corresponding water was collected in
      a Dean-Stark receiver. This procedure permits fast and efficient determination of
      the water content of olives. Reliability and reproducibility were evaluated using
      statistical analyses. Different matrices were then used with MADS and the results
      were compared to CDS. Water determination from olives with MADS was better than
      that with CDS in terms of energy saving, rapidity (10 min versus 120 min),
      reproducibility, and cleanliness.

PMID- 19110096
TI  - Development of on-line single-drop micro-extraction sequential injection system
      for electrothermal atomic absorption spectrometric determination of trace metals.
AB  - A novel automatic sequential injection (SI) single-drop micro-extraction (SDME)
      system is proposed as versatile approach for on-line metal preconcentration
      and/or separation. Coupled to electrothermal atomic absorption spectrometry
      (ETAAS) the potentials of this SI scheme are demonstrated for trace cadmium
      determination in water samples. A non-charged complex of cadmium with ammonium
      diethyldithiophosphate (DDPA) was produced and extracted on-line into a 60 microL
      micro-drop of di-isobutyl ketone (DIBK). The extraction procedure was performed
      into a newly designed flow-through extraction cell coupled on a sequential
      injection manifold. As the complex Cd(II)-DDPA flowed continuously around the
      micro-droplet, the analyte was extracting into the solvent micro-drop. All the
      critical parameters were optimized and offered good performance characteristics
      and high preconcentration ratios. For 600 s micro-extraction time, the
      enhancement factor was 10 and the sampling frequency was 6h(-1). The detection
      limit was 0.01 microg L(-1) and the precision (RSD at 0.1 microg L(-1) of
      cadmium) was 3.9%. The proposed method was evaluated by analyzing certified
      reference material.

PMID- 19110095
TI  - Headspace in-drop derivatization of carbonyl compounds for their analysis by high
      performance liquid chromatography-diode array detection.
AB  - A simple and rapid method has been reported for the determination of carbonyl
      compounds involving sample preparation by headspace single drop microextraction
      using 1-butanol as extraction solvent containing 2,4-dinitrophenylhydrazine for
      hydrazone formation, and direct transfer of the drop into the injector for high
      performance liquid chromatography with diode array detection. An angle-cut
      polytetrafluoroethylene sleeve, 3mm x 0.5mm, was fixed at the tip of the syringe
      needle and this allowed the use of 7 microL drop of solvent drop for extraction
      and derivatization. The procedure has been optimized with respect to suitable
      solvent for headspace drop formation, drop volume, concentration of reagent,
      sample temperature, reaction time, and headspace-to-sample volume ratio. The
      method has been validated when rectilinear relationship was obtained between the
      amount of analyte and peak area ratio of hydrazones in the range 0.01-15 mg L(
      1), the correlation coefficient over 0.996-0.999, and the limit of detection in
      the range 1.7-24.1 microg L(-1). Spiked real samples have been analyzed with
      adequate accuracy, and application has been demonstrated of the method for
      analysis of carbonyl compounds formed as oxidation products.

PMID- 19110097
TI  - Nuclear magnetic resonance and liquid chromatography-mass spectrometry combined
      with an incompleted separation strategy for identifying the natural products in
      crude extract.
AB  - NMR and LC-MS combined with an incompleted separation strategy were proposed to
      the simultaneous structure identification of natural products in crude extracts,
      and a novel method termed as NMR/LC-MS parallel dynamic spectroscopy (NMR/LC-MS
      PDS) was developed to discover the intrinsic correlation between retention time
      (Rt), mass/charge (m/z) and chemical shift (delta) data of the same constituent
      from mixture spectra by the co-analysis of parallelly visualized
      multispectroscopic datasets from LC-MS and (1)H NMR. The extracted ion
      chromatogram (XIC) and (1)H NMR signals deriving from the same individual
      constituent were correlated through fraction ranges and intensity changing
      profiles in NMR/LC-MS PDS spectrum due to the signal amplitude co-variation
      resulted from the concentration variation of constituents in a series of
      incompletely separated fractions. NMR/LC-MS PDS was applied to identify 12
      constituents in an active herbal extract including flavonol glycosides, which was
      separated into a series of fractions by flash column chromatography. The
      complementary spectral information of the same individual constituent in the
      crude extract was discovered simultaneously from mixture spectra. Especially, two
      groups of co-eluted isomers were identified successfully. The results
      demonstrated that NMR/LC-MS PDS combined with the incompleted separation strategy
      achieved the similar function of on-line LC-NMR-MS analysis in off-line mode and
      had the potential for simplifying and accelerating the analytical routes for
      structure identification of constituents in herbs or their active extracts.

PMID- 19110098
TI  - Near-ultraviolet femtosecond laser ionization of dioxins in gas
      chromatography/time-of-flight mass spectrometry.
AB  - Gas chromatography/multiphoton ionization/time-of-flight mass spectrometry
      (GC/MPI/TOF-MS) was applied to the trace analysis of polychlorinated dibenzo-p
      dioxins and polychlorinated dibenzofurans (PCDD/Fs). To determine the optimum
      wavelength for analysis of PCDD/Fs, the wavelength of the femtosecond laser
      utilized for multiphoton ionization was converted to near-ultraviolet status
      using stimulated Raman scattering. A femtosecond laser emitting at 300 nm
      completely eliminated the background signal arising from the bleeding compounds
      generated from a stationary phase of the capillary column in GC.

PMID- 19110099
TI  - Mass-independent isotopic fractionation of tin in chemical exchange reaction
      using a crown ether.
AB  - Tin isotopes were fractionated by the liquid-liquid extraction technique with a
      crown ether, dicyclohexano-18-crown-6. The isotopic ratios of (m)Sn/(120)Sn (m:
      116, 117, 118, 119, 122 and 124) were measured by multi-collector inductively
      coupled plasma spectrometry (MC-ICP-MS) on a Nu Plasma 500 with a precision
      better than 0.05 permil amicro(-1) on each isotopic ratio. Odd atomic mass
      isotopes ((117)Sn and (119)Sn) showed depletions compared to the even atomic mass
      isotopes ((116)Sn, (118)Sn, (122)Sn and (124)Sn). We show that this odd-even
      staggering property originates from the nuclear field shift effect. The
      contribution of the nuclear field shift effect to the observed isotope enrichment
      factor was estimated to be approximately 35%.

PMID- 19110100
TI  - Evaluation of substrate performance for a microbial diagnostic microarray using a
      four parameter ranking.
AB  - The impact of substrates for probe immobilization was studied using a microbial
      diagnostic microarray consisting of probes designed against the pmoA genes of
      methanotrophs and functionally related bacteria. The proprietary ARChip Epoxy was
      compared to seven epoxy-modified competitor slides, and one porous 3D,
      furthermore two substrates recommended for oligoprobes without description of the
      surface chemistry. The diagnostic microarray on Cel silylated aldehyde (CSS)
      slide was used as a reference for this comparison as it was actually used for
      assay development and validation. The suitability of binding chemistries for
      microarrays was evaluated by specificity, signal, and inter- and intra-slide
      precision and ranked accordingly. The performance of four epoxy substrates
      (ARChip Epoxy, Cel Epoxy, Corning Epoxy, sciChip) and Spot On slides has proved
      satisfactory and comparable to the reference Cel CSS in that inter-slide
      precision was between 8% and 18% CV, intra-slide precision below 30%,
      respectively. The four parameter ranking shows great promise of providing deeper
      insight in the performance of materials and protocols tested.

PMID- 19110101
TI  - Chemiluminometric enzyme-linked immunosorbent assays (ELISA)-on-a-chip biosensor
      based on cross-flow chromatography.
AB  - A chemiluminometric biosensor system for point-of-care testing has been developed
      using an immuno-chromatographic assay combined with an enzyme (e.g., horseradish
      peroxidase) tracer that produces a light signal measurable on a simple detector.
      Cross-flow chromatography, a method previously investigated by our laboratory,
      was utilized in order to accomplish sequential antigen-antibody binding and
      signal generation. This enzyme-linked immunosorbent assay (ELISA) was effectively
      carried out on a plastic chip that was redesigned to simplify the fabrication
      process. To enhance the sensitivity, biotin-streptavidin capture technology was
      employed in preparing an immuno-strip that was then incorporated onto the chip in
      order to generate the ELISA-on-a-chip (EOC) biosensor. Samples containing cardiac
      troponin I (cTnI) were analyzed using the EOC. A chemiluminescent signal
      proportional to the analyte concentration was produced by adding a luminogenic
      substrate to the tracer enzyme complexed with the analyte on the chip. The
      luminescent signal was detected in a dark chamber mounted with a cooled charge
      coupled device and the signal was converted to optical density for
      quantification. This EOC biosensor system was capable of detecting cTnI present
      in serum at concentrations as low as 0.027 ng mL(-1), 30 times lower than those
      measured using the conventional rapid test kit with colloidal gold as the tracer.
      In addition, the final data was acquired within 30s after the addition of the
      enzyme substrate, which was faster than the detection time required when using a
      colorimetric substrate with the same tracer enzyme.

PMID- 19110102
TI  - Glycidyl methacrylate-co-N-vinyl-2-pyrrolidone coated polypropylene strips:
      synthesis, characterization and standardization for dot-enzyme linked
      immunosorbent assay.
AB  - Glycidyl methacrylate and N-vinyl-2-pyrrolidone (GMA-co-NVP) copolymers with
      various GMA:NVP ratios were synthesized by solution polymerization technique in
      toluene using 2,2'-azobisisobutyronitrile (AIBN) as free radical initiator and
      dip coated onto polypropylene strips. The copolymer composition in polymeric
      coatings was confirmed by proton NMR spectroscopy. Various techniques like FTIR,
      SEM and contact angle were used for surface characterization of the polymer
      coatings. These polymer coated strips were evaluated and standardized for their
      application in dot-ELISA in two steps. In first step, specificity, sensitivity
      and reproducibility of the assay on developed polymer coated strips was evaluated
      through a model system using rabbit anti-goat IgG, goat anti-rabbit IgG and goat
      anti-rabbit IgG HRP (horseradish peroxidase)-conjugate. Polymer coating with GMA
      NVP mol% ratio of 78:22 was able to detect rabbit anti-goat IgG antibody at a
      concentration as low as 2 ng mL(-1) with 1% BSA as blocking agent using
      antispecies IgG peroxidase conjugate diluted 1500 times. In the second step, the
      sensitivity and specificity of the developed system was established with human
      blood and finally used to identify the source of mosquito blood meal which is an
      important parameter in epidemiological studies, particularly in determining the
      role of mosquito in malaria transmission. The time duration of standardized assay
      with developed polymer coated strips was cut down to one hour compared to the 3
      4h required in usual dot-ELISA.

PMID- 19110103
TI  - A highly sensitive enzyme immunoassay for evaluation of 2'-deoxycytidine plasma
      level as a prognostic marker for breast cancer chemotherapy.
AB  - A highly sensitive competitive enzyme immunoassay (EIA) has been developed and
      validated for the determination of the plasma level of 2'-deoxycytidine (dCyd),
      the potential prognostic marker for breast cancer chemotherapy. This assay
      employed a monoclonal antibody that recognizes dCyd with a high specificity, and
      5'-succinyl-dCyd (5'sdCyd) conjugate of bovine serum albumin (5'sdCyd-BSA)
      immobilized onto microplate wells as a solid phase. The assay involved a
      competitive binding reaction between dCyd, in plasma sample, and the immobilized
      5'sdCyd-BSA for the binding sites of the anti-dCyd antibody. The bound antibody
      was quantified with horseradish peroxidase-labeled anti-immunoglobulin second
      antibody and 3,3',5,5'-tetramethylbenzidine as a peroxidase substrate. The
      concentration of dCyd in the sample was quantified by its ability to inhibit the
      binding of the antibody to the immobilized 5'sdCyd-BSA and subsequently the color
      formation in the assay. The assay limit of detection was 8 nM and the effective
      working range at relative standard deviations (R.S.D.s) of <or=10% was 20-800 nM.
      No cross-reactivity from the structurally related nucleobases, nucleosides, and
      nucleotides was observed in the proposed assay. Mean analytical recovery of added
      dCyd was 98-100+/-3.2-8.2%. The precision of the assay was satisfactory; R.S.D.
      was 3.4-4.2 and 4.3-8.9% for intra- and inter-assay precision, respectively. The
      proposed EIA was compared favorably with HPLC method in its ability to accurately
      measure dCyd spiked into plasma samples. The analytical procedure is convenient,
      and one can analyze 200 samples per working day, facilitating the processing of
      large-number batch of samples. The proposed EIA is expected to contribute in
      further evaluation of dCyd as a prognostic marker for breast cancer chemotherapy
      and elucidation of the role of dCyd in various biological and biochemical
      systems.

PMID- 19110104
TI  - Chemically-modified activated carbon with ethylenediamine for selective solid
      phase extraction and preconcentration of metal ions.
AB  - A new method that utilizes ethylenediamine-modified activated carbon (AC-EDA) as
      a solid-phase extractant has been developed for simultaneous preconcentration of
      trace Cr(III), Fe(III), Hg(II) and Pb(II) prior to the measurement by inductively
      coupled plasma optical emission spectrometry (ICP-OES). The new sorbent was
      prepared by oxidative surface modification. Experimental conditions for effective
      adsorption of trace levels of Cr(III), Fe(III), Hg(II) and Pb(II) were optimized
      with respect to different experimental parameters using batch and column
      procedures in detail. The optimum pH value for the separation of metal ions
      simultaneously on the new sorbent was 4.0. Complete elution of absorbed metal
      ions from the sorbent surface was carried out using 3.0 mL of 2% (%w/w) thiourea
      and 0.5 mol L(-1) HCl solution. Common coexisting ions did not interfere with the
      separation and determination of target metal ions. The maximum static adsorption
      capacity of the sorbent at optimum conditions was found to be 39.4, 28.9, 60.5
      and 49.9 mg g(-1) for Cr(III), Fe(III), Hg(II) and Pb(II), respectively. The time
      for 94% adsorption of target metal ions was less than 2 min. The detection limits
      of the method was found to be 0.28, 0.22, 0.09 and 0.17 ng mL(-1) for Cr(III),
      Fe(III), Hg(II) and Pb(II), respectively. The precision (R.S.D.) of the method
      was lower 4.0% (n=8). The prepared sorbent as solid-phase extractant was
      successfully applied for the preconcentration of trace Cr(III), Fe(III), Hg(II)
      and Pb(II) in natural and certified samples with satisfactory results.

PMID- 19110105
TI  - Development of high performance liquid chromatography method for lacidipine in
      rabbit serum: application to pharmacokinetic study.
AB  - A simple and sensitive high performance liquid chromatographic (HPLC) method for
      quantification of lacidipine (LCDP) in rabbit serum was developed and validated.
      LCDP and internal standard (IS), felodipine were extracted into n-hexane and
      dichloromethane (70:30) solvent system and separated using an isocratic mobile
      phase, on an Inertsil C18 column. The effluent was monitored by UV detector at
      240 nm and at a flow rate of 1.0 mL min(-1). The linearity range of proposed
      method was 1-500 ng mL(-1). The intra-day and inter-day coefficient of variation
      and percent error values of the assay method were less than 15% and mean recovery
      was more than 94 and 95% for LCDP and IS, respectively and the method was found
      to be precise, accurate, and specific during the study. The method was
      successfully applied for pharmacokinetic study of lacidipine after application of
      LCDP microemulsion gel in rabbits.

PMID- 19110106
TI  - A simplified version of the total Kjeldahl nitrogen method using an ammonia
      extraction ultrasound-assisted purge-and-trap system and ion chromatography for
      analyses of geological samples.
AB  - The total Kjeldahl nitrogen (TKN) method was simplified by using a manifold
      connected to a purge-and-trap system immersed into an ultrasonic (US) bath for
      simultaneous ammonia (NH(3)) extraction from many previously digested samples.
      Then, ammonia was collected in an acidic solution, converted to ammonium
      (NH(4)(+)), and finally determined by ion chromatography method. Some variables
      were optimized, such as ultrasonic irradiation power and frequency, ultrasound
      assisted NH(3) extraction time, NH(4)(+) mass and sulfuric acid concentration
      added to the NH(3) collector flask. Recovery tests revealed no changes in the pH
      values and no conversion of NH(4)(+) into other nitrogen species during the
      irradiation of NH(4)Cl solutions with 25 or 40 kHz ultrasonic waves for up to 20
      min. Sediment and oil free sandstone samples and soil certified reference
      materials (NCS DC 73319, NCS DC 73321 and NCS DC 73326) with different total
      nitrogen concentrations were analysed. The proposed method is faster, simpler and
      more sensitive than the classical Kjeldahl steam distillation method. The time
      for NH(3) extraction by the US-assisted purge-and-trap system (20 min) was half
      of that by the Kjeldahl steam distillation (40 min) for 10 previously digested
      samples. The detection limit was 9 microg g(-1)N, while for the Kjeldahl
      classical/indophenol method was 58 microg g(-1)N. Precision was always better
      than 13%. In the proposed method, carcinogenic reagents are not used, contrarily
      to the indophenol method. Furthermore, the proposed method can be adapted for
      fixed-NH(4)(+) determination.

PMID- 19110107
TI  - Application of dispersive liquid-liquid microextraction for the analysis of
      triazophos and carbaryl pesticides in water and fruit juice samples.
AB  - In this work, a simple, rapid and sensitive sample pretreatment technique,
      dispersive liquid-liquid microextraction (DLLME) coupled with high performance
      liquid chromatography-fluorescence detection (HPLC-FLD), has been developed to
      determine carbamate (carbaryl) and organophosphorus (triazophos) pesticide
      residues in water and fruit juice samples. Parameters, affecting the DLLME
      performance such as the kind and volume of extraction and dispersive solvents,
      extraction time and salt concentration, were studied and optimized. Under the
      optimum extraction conditions (extraction solvent: tetrachloroethane, 15.0
      microL; dispersive solvent: acetonitrile, 1.0 mL; no addition of salt and
      extraction time below 5s), the performance of the proposed method was evaluated.
      The enrichment factors for the carbaryl and triazophos were 87.3 and 275.6,
      respectively. The linearity was obtained in the concentration range of 0.1-1000
      ng mL(-1) with correlation coefficients from 0.9991 to 0.9999. The limits of
      detection (LODs), based on signal-to-noise ratio (S/N) of 3, ranged from 12.3 to
      16.0 pg mL(-1). The relative standard deviations (RSDs, for 10 ng mL(-1) of
      carbaryl and 20 ng mL(-1) of triazophos) varied from 1.38% to 2.74% (n=6). The
      environmental water (at the fortified level of 1.0 ng mL(-1)) and fruit juice
      samples (at the fortified level of 1.0 and 5.0 ng mL(-1)) were successfully
      analyzed by the proposed method, and the relative recoveries of them were in the
      range of 80.4-114.2%, 89.8-117.9% and 86.3-105.3%, respectively.

PMID- 19110108
TI  - Biopartitioning micellar chromatography to predict blood to lung, blood to liver,
      blood to fat and blood to skin partition coefficients of drugs.
AB  - Biopartitioning micellar chromatography (BMC), a mode of micellar liquid
      chromatography that uses micellar mobile phases of Brij35 in adequate
      experimental conditions, has demonstrated to be useful in mimicking the drug
      partitioning process into biological systems. In this paper, the usefulness of
      BMC for predicting the partition coefficients from blood to lung, blood to liver,
      blood to fat and blood to skin is demonstrated. PLS2 and multiple linear
      regression (MLR) models based on BMC retention data are proposed and compared
      with other ones reported in bibliography. The proposed models present better or
      similar descriptive and predictive capability.

PMID- 19110109
TI  - Purge efficiency in the determination of trihalomethanes in water by purge-and
      trap gas chromatography.
AB  - Purge-and-trap gas chromatography-mass spectrometry (PT-GC-MS) has become an
      accepted method for the analysis of trihalomethanes (THMs) in water. The purge
      and-trap technique is based on an efficient transfer of volatile organic
      compounds from the liquid (contained in the purge chamber) to the gaseous phase
      by bubbling with an inert gas. The aim of this work was to study the purge
      system's efficiency by means of several consecutive purge cycles lasting 11 min
      each of the same liquid sample. The concentration range chosen of THMs was very
      wide [5-200 microg L(-1)]. The inert gas flow rate was 40 mL min(-1), and
      experiments were performed at temperatures of 25, 35 and 50 degrees C. Bromoform
      (CHBr(3)), the least volatile compound, needed 19 cycles to be purged
      quantitatively at a concentration of 200 microg L(-1) and only 7 cycles at 5
      microg L(-1) for a 25 mL sample at 25 degrees C. Chloroform (CHCl(3)), the most
      volatile compound, required 4 cycles to be fully extracted at 200 microg L(-1)
      and 2 at 5 microg L(-1). Finally, Novak's theoretical model, based on the
      distribution constant between gas and liquid phases, was used to correlate the
      THMs purging extraction data.

PMID- 19110110
TI  - Recent trends in total reflection X-ray fluorescence spectrometry for biological
      applications.
AB  - This review is focused on the application of total reflection X-ray fluorescence
      (TXRF) spectrometry in the field of biological research. In the last decade, most
      papers were published by authors who applied laboratory-scale TXRF equipments.
      The application of synchrotron radiation as excitation source (SR-TXRF) shows a
      slowly increasing tendency. In the cited papers the micro-, trace and
      multielement capability of these TXRF techniques was demonstrated in the clinical
      and medical laboratory practice, as well as in various plant physiological
      studies. For speciation of elements in biological matrices, the TXRF was used as
      element specific detector following an off-line separation step (e.g., thin layer
      chromatography, high performance liquid chromatography), however, these off-line
      methods are not competitive with the on-line coupled HPLC-inductively coupled
      plasma mass spectrometry.

PMID- 19110111
TI  - Short transient signals, a challenge for inductively coupled plasma mass
      spectrometry, a review.
AB  - The ability to acquire and handle short transient signals is key in order to open
      new applications for inductively coupled plasma mass spectrometry (ICP-MS), for
      example, in life sciences. Technological and methodological achievements are
      reviewed to show challenges and capabilities of short transients in ICP-MS
      technology or hyphenated techniques. The dynamic processes in the plasma need to
      be controlled or observed to assure quality of quantitative results. Most precise
      instrumentation is to date multiple collector sector field MS but drifting
      isotope ratios are observed in transient signals using these instruments, thus
      limiting precision of such measurements and leaving unknowns in quantitative
      results. TOFMS in principle provides fast simultaneous multi-element detection,
      scanning instruments like quadrupole MS or scanning sector field MS are
      fundamentally restricted. However, new commercial ICP-MS instruments can be
      expected in the near future, making short transients more and more attractive to
      shorten acquisition times and to increase signal to noise ratio of element
      analyses.

PMID- 19110112
TI  - Matrix effects on the multi-collector inductively coupled plasma mass
      spectrometric analysis of high-precision cadmium and zinc isotope ratios.
AB  - Resin-derived contaminants added to samples during column chemistry are shown to
      cause matrix effects that lead to inaccuracy in multi-collector inductively
      coupled plasma mass spectrometry measurement of small natural variations in Cd
      and Zn isotopic compositions. These matrix effects were evaluated by comparing
      pure Cd and Zn standards and standards doped with bulk column blank from the
      anion exchange chromatography procedure. Doped standards exhibit signal
      enhancements (Cd, Ag, Zn and Cu), instrumental mass bias changes and inaccurate
      isotopic compositions relative to undoped standards, all of which are attributed
      to the combined presence of resin-derived organics and inorganics. The matrix
      effect associated with the inorganic component of the column blanks was evaluated
      separately by doping standards with metals at the trace levels detected in the
      column blanks. Mass bias effects introduced by the inorganic column blank matrix
      are smaller than for the bulk column blank matrix but can still lead to
      significant changes in ion signal intensity, instrumental mass bias and isotopic
      ratios. Chemical treatment with refluxed HNO(3) or HClO(4)/HNO(3) removes resin
      derived organic components resulting in matrix effects similar in magnitude to
      those associated with the inorganic component of the column blank. Mass bias
      correction using combined external normalization-SSB does not correct for these
      matrix effects because the instrumental mass biases experienced by Cd and Zn are
      decoupled from those of Ag and Cu, respectively. Our results demonstrate that ion
      exchange chromatography and associated resin-derived contaminants can be a source
      of error in MC-ICP-MS measurement of heavy stable element isotopic compositions.

PMID- 19110113
TI  - Real time and in situ determination of lead in road sediments using a man
      portable laser-induced breakdown spectroscopy analyzer.
AB  - In situ, real time levels of lead in road sediments have been measured using a
      man-portable laser-induced breakdown spectroscopy analyzer. The instrument
      consists of a backpack and a probe housing a Q-switched Nd:YAG laser head
      delivering 50 mJ per pulse at 1064 nm. Plasma emission was collected and
      transmitted via fiber optic to a compact cross Czerny-Turner spectrometer
      equipped with a linear CCD array allocated in the backpack together with a
      personal computer. The limit of detection (LOD) for lead and the precision
      measured in the laboratory were 190 microg g(-1) (calculated by the 3 sigma
      method) and 9% R.S.D. (relative standard deviation), respectively. During the
      field campaign, averaged Pb concentration in the sediments were ranging from 480
      microg g(-1) to 660 microg g(-1) depending on the inspected area, i.e. the
      entrance, the central part and the exit of the tunnel. These results were
      compared with those obtained with flame-atomic absorption spectrometry (flame
      AAS). The relative error, expressed as [100(LIBS result-flame AAS result)/(LIBS
      result)], was approximately 14%.

PMID- 19110114
TI  - Pattern recognition of Chinese flue-cured tobaccos by an improved and simplified
      K-nearest neighbors classification algorithm on near infrared spectra.
AB  - In tobacco industry of China, tobacco leaves are classified and managed in terms
      of their cultivation areas and plant parts of tobacco-stalks. However, sometimes
      intentionally or involuntary mislabeling cultivation areas, blending tobacco
      plant parts would occur into tobacco market. The error will affect the style and
      quality of cigarettes. In the present work, more than 1000 Chinese flue-cured
      tobacco leaf samples, which have 12 genotypes and cultivated from 5 to 10 regions
      of China in 2003 and 2004, have been discriminated by means of an improved and
      simplified KNN classification algorithm (IS-KNN) based on near infrared (NIR)
      spectra. An original method of optimizing number of significant principal
      components (PCs) based on analysis of error and cross-validation was advanced.
      Compared with conventional pattern recognition methods KNN, NN, LDA and PLS-DA,
      IS-KNN exhibits good adaptability in discrimination of complicated Chinese flue
      cured tobaccos. The practice in this work shows that optimized number of PCs and
      performance of classification models are closely relative to complicated extent
      of samples but not to number of categories or samples. The results demonstrated
      the usefulness of NIR spectra combined with chemometrics as an objective and
      rapid method for the authentication and identification of tobacco leaves or other
      kinds of powder samples.

PMID- 19110115
TI  - CYP450 2B4 covalently attached to carbon and gold screen printed electrodes by
      diazonium salt and thiols monolayers.
AB  - An easy covalent immobilization method used to develop enzyme biosensors based on
      carbon and gold screen printed electrodes (SPCEs and gold SPEs) is described. The
      linkage of biomolecules through 4-nitrobenzenediazonium tetrafluoroborate,
      mercaptopropionic acid and thioctic acid monolayers has been attempted using bare
      SPCEs and gold SPEs, as well as gold nanoparticles (AuNPs) modified SPCEs and
      gold SPEs. Direct covalent attachment of Cytochrome P450 2B4 (CYP450 2B4) to the
      transducer has been carried out by carbodiimide and hydroxysuccinimide.
      Experimental variables in the immobilization process and in the
      chronoamperometric determination of Phenobarbital (PB) have been optimized by the
      experimental design methodology. Reproducibility of the different biosensors has
      been checked under the optimum conditions, yielding values lower than 6%. Their
      performances have been shown by the determination of PB in pharmaceutical drugs.

PMID- 19110116
TI  - Polydimethylsiloxane/polypyrrole stir bar sorptive extraction and liquid
      chromatography (SBSE/LC-UV) analysis of antidepressants in plasma samples.
AB  - A new polymeric coating consisting of a dual-phase, polydimethylsiloxane (PDMS)
      and polypyrrole (PPY) was developed for the stir bar sorptive extraction (SBSE)
      of antidepressants (mirtazapine, citalopram, paroxetine, duloxetine, fluoxetine
      and sertraline) from plasma samples, followed by liquid chromatography analysis
      (SBSE/LC-UV). The extractions were based on both adsorption (PPY) and sorption
      (PDMS) mechanisms. SBSE variables, such as extraction time, temperature, pH of
      the matrix, and desorption time were optimized, in order to achieve suitable
      analytical sensitivity in a short time period. The PDMS/PPY coated stir bar
      showed high extraction efficiency (sensitivity and selectivity) toward the target
      analytes. The quantification limits (LOQ) of the SBSE/LC-UV method ranged from 20
      ng mL(-1) to 50 ng mL(-1), and the linear range was from LOQ to 500 ng mL(-1),
      with a determination coefficient higher than 0.99. The inter-day precision of the
      SBSE/LC-UV method presented a variation coefficient lower than 15%. The
      efficiency of the SBSE/LC-UV method was proved by analysis of plasma samples from
      elderly depressed patients.

PMID- 19110117
TI  - Integrated analysis of serum and liver metabonome in liver transplanted rats by
      gas chromatography coupled with mass spectrometry.
AB  - In this paper, we present a metabonomic method for the investigation of abnormal
      metabolic process in both serum and liver tissue of liver transplanted rats.
      Syngeneic transplantation was performed on male Lewis rats. The serum and grafted
      liver on day 1, 3, and 7 post-transplant were collected to analyze endogenous
      metabolites using gas chromatography coupled with mass spectrometry (GC-MS). The
      method was validated with acceptable linearity, precision, and repeatability.
      Thirty-four metabolites in serum and 29 metabolites in liver were identified.
      Results of correlation analysis illustrated metabolites with similar function
      exhibited similar variations in liver and serum. The data processed by principle
      component analysis (PCA) showed time-dependent biochemical variations. As a
      consequence, the present study may offer specific putative pathways in the
      pathophysiological mechanism of orthotopic liver transplantation.

PMID- 19110118
TI  - Selective spectrofluorimetric determination of glutathione in clinical and
      biological samples using 1,3,5,7-tetramethyl-8-phenyl-(2-maleimide)
      difluoroboradiaza-s-indacene.
AB  - This work reports the development of a selective, sensitive and rapid
      spectrofluorimetric method for the determination of reduced glutathione (GSH) in
      the presence of relatively high levels of cysteine (Cys) in clinical and
      biological samples using 1,3,5,7-tetramethyl-8-phenyl-(2-maleimide)
      difluoroboradiaza-s-indacene (TMPAB-o-M). The fluorescence from TMPAB-o-M is
      strongly quenched by its maleimide moiety, but after reaction with thiol, the
      fluorescence is restored with a 350-fold intensity increase (fluorescence quantum
      yield from 0.002 to 0.73). In H(3)Cit-Na(2)HPO(4) buffer (pH 7.40), the
      derivatization is completed in just 5 min under 37 degrees C. The linear range is
      0.005-0.2 micromol L(-1), with detection limit of 1.1 x 10(-10)mol L(-1) (signal
      to-noise ratio=3). Almost all amino acids, including Cys, impose no interference
      even if present at relatively high concentrations (amino acids:GSH=100:1,
      Cys:GSH=1:1, molar ratio, C(GSH)=3 x 10(-7)mol L(-1)). The sample can be used
      directly without further treatment after the protein is removed. The developed
      method is precise with a relative standard deviation (R.S.D.) lower than 5.0%
      (n=6) and has been applied to the determination of GSH in human blood and pig's
      liver with recoveries between 94.4 and 105.6%.

PMID- 19110119
TI  - A high throughput chemiluminescence method for determination of chemical oxygen
      demand in waters.
AB  - A novel and high throughput chemiluminescence (CL) method for determination of
      chemical oxygen demand (COD) in water sample was originally developed based on
      potassium permanganate-glutaraldehyde CL system. With this method, dissolved
      organic matter in water samples was digested by excess acid potassium
      permanganate, the reacted mixture solutions containing surplus KMnO(4) were added
      in wells of a 96-well plate, followed by injection of glutaraldehyde in the
      wells, and CL was then produced along with the reaction of the added
      glutaraldehyde with the surplus KMnO(4) and detected by a photomultiplier tube
      (PMT). The difference (DeltaI) between the CL intensity for distilled water and
      that for sample water was proportional to the COD value of water sample. The
      calibration graph was linear in the range of 0.16-19.24 mg L(-1) with a detection
      limit of 0.1 mg L(-1). A complete analysis could be performed in 40 min including
      digestion and detection, giving a very high throughput of 3 x 96 samples in about
      60 min. Compared with the conventional methods, this method is simple and
      sensitive and consumes very limited and cheap reagents. Owing to its rapid,
      automatic, high throughput and low cost characteristics, the presented CL method
      has been applied successfully to the determination of COD in real water samples
      (n=32) with satisfactory results.

PMID- 19110120
TI  - A hydrogel based fluorescent micro array used for the characterization of liquid
      analytes.
AB  - A fluorimetric micro spot array using non-specific recognition function is
      described for the analysis of liquid samples. The array was composed of binary
      mixtures of various fluorescence dyes which were embedded in a hydrogel matrix.
      The interactions between the fluorescent dyes and their molecular surrounding
      inside the hydrogel, influence their fluorescence wave length and intensities.
      The array was used for the characterization of solvent mixtures. Developed
      fluorescence patterns of the complete array as well as the fluorescence intensity
      changes of single spots were analysed. It was proven, that specific analytical
      information can be gained using this non-specific recognition approach. The
      identification of some alcoholic beverages is described as an example of the
      application of this method when used for quality control purposes. Analogous to
      the appellation "electronic nose" and "electronic tongue" the described micro
      spot array acts as an "optochemical tongue".

PMID- 19110121
TI  - Biosensor system for continuous glucose monitoring in fish.
AB  - A biosensor system was developed for continuous estimation of blood glucose in
      fish. Because it is difficult to measure blood components in real-time due to
      decreased sensor output resulting from blood coagulation and coalescing blood
      proteins at the sensor placement site, we used the eyeball scleral interstitial
      fluid (EISF) as the site of sensor implantation. Evaluation of the relationship
      between EISF and blood glucose concentrations revealed that the blood glucose
      concentration correlated closely with the EISF glucose concentration
      (y=2.2996+0.9438x, R=0.960, n=112). To take advantage of the close correlation
      between blood and EISF glucose, we prepared a needle-type enzyme sensor for
      implantation in the fish sclera using a flexible wire electrode. The sensor
      provided a rapid response, good linearity, and reproducibility. Continuous
      glucose monitoring could be carried out by implanting this needle-type glucose
      sensor onto the eye. The findings indicated that the glucose concentration
      increased with sensor output current over time, and that changes in the blood
      glucose were continuously reflected in the EISF. The glucose concentration was
      estimated based on the one-point or two-point calibration methods. The two-point
      calibration method yielded the most accurate glucose monitoring (blood glucose
      range of 70-420 mg dL(-1)) over 160 min. Sensor-estimated glucose and whole blood
      glucose values were highly correlated (y=0.4401+0.8656x, R=0.958).

PMID- 19110123
TI  - Multiplex detection of tumor markers with photonic suspension array.
AB  - A novel photonic suspension array was developed for multiplex immunoassay. The
      carries of this array were silica colloidal crystal beads (SCCBs). The codes of
      these carriers are the characteristic reflection peak originated from their
      structural periodicity, and therefore they do not suffer from fading, bleaching,
      quenching, and chemical instability. In addition, because no dyes or materials
      related with fluorescence are included, the fluorescence background of SCCBs is
      very low. With a sandwich format, the proposed suspension array was used for
      simultaneous multiplex detection of tumor markers in one test tube. The results
      showed that the four tumor markers, alpha-fetoprotein (AFP), carcinoembryonic
      antigen (CEA), carcinoma antigen 125 (CA 125) and carcinoma antigen 19-9 (CA 19
      9) could be assayed in the ranges of 1.0-500 ng mL(-1), 1.0-500 ng mL(-1), 1.0
      500 U mL(-1) and 3.0-500 U mL(-1) with limits of detection of 0.68 ng mL(-1),
      0.95 ng mL(-1), 0.99 U mL(-1) and 2.30 U mL(-1) at 3 sigma, respectively. The
      proposed array showed acceptable accuracy, detection reproducibility, storage
      stability and the results obtained were in acceptable agreement with those from
      parallel single-analyte test of practical clinical sera. This technique provides
      a new strategy for low cost, automated, and simultaneous multiplex immunoassay.

PMID- 19110122
TI  - A label-free fluorescence sensor for probing the interaction of oligonucleotides
      with target molecules.
AB  - This paper describes a universal, label-free fluorescence sensor that gauges the
      interaction of oligonucleotides with their targets. The sensor is based on
      supramolecular assemblies formed by oligonucleotides (polyanions) and small
      molecule cation surfactant in aqueous solution. The environmentally dependent dye
      pyrene, encapsulated in the apolar interiors of the assemblies via hydrophobic
      interactions works as the fluorescence probe. Target binding causes the
      conformational change of the oligonucleotides, which results in disorganization
      of supramolecular assemblies, release of pyrene into the aqueous solution and
      subsequent quenching of its fluorescence. The kinetic processes (including the
      formation of supramolecular assemblies and the release of pyrenes after adding
      the targets) were investigated. The fluorescence decreases of pyrenes are
      proportional to the concentrations of targets within the linear ranges. This
      label-free fluorescence system is simple, convenient, low cost, and can serve as
      an alternative tool for interaction studies of oligonucleotides with their
      targets, especially with small molecular targets.

PMID- 19110124
TI  - Development of electrochemical sensors for nano scale Tb(III) ion determination
      based on pendant macrocyclic ligands.
AB  - The two macrocyclic pendant ligands 3,4,5:12,13,14-dipyridine-2,6,11,15
      tetramethyl-1,7,10,16-tetramethylacrylate-1,4,7,10,13,16-hexaazacyclooctadeca
      3,13-di ene (L(1)) and 3,4,5:12,13,14-dipyridine-2,6,11,15-tetramethyl-1,7,10,16
      tetra(2-cyano ethane)-1,4,7,10,13,16-hexaazacyclooctadeca-3,13-diene (L(2)) have
      been synthesized and explored as neutral ionophores for preparing
      poly(vinylchloride) (PVC) based membrane sensors selective to Tb(III) ions.
      Effects of various plasticizers and anion excluders were studied in detail and
      improved performance was observed. The best performance was obtained for the
      membrane sensor having a composition of L(1): PVC:1-CN:NaTPB in the ratio of 6:
      32: 58: 4 (w/w; mg). The performance of the membrane based on L(1) was compared
      with polymeric membrane electrode (PME) as well as with coated graphite electrode
      (CGE). The electrodes exhibit Nernstian slope for Tb(3+) ions with limits of
      detection of 3.4 x 10(-8)mol L(-1) for PME and 5.7 x 10(-9)mol L(-1) for CGE. The
      response time for PME and CGE was found to be 10s and 8s, respectively. The
      potentiometric responses are independent of the pH of the test solution in the pH
      range 3.0-7.5 for PME and 2.0-8.5 for CGE. The CGE has found to work
      satisfactorily in partially non-aqueous media upto 30% (v/v) content of methanol,
      ethanol and 20% (v/v) content of acetonitrile and could be used for a period of 5
      months. The CGE was used as indicator electrode in the potentiometric titration
      of Tb(3+) ions with EDTA and in determination of fluoride ions in various
      samples. It can also be used in direct determination of Tb(3+) ions in tap water
      and various binary mixtures with quantitative results.

PMID- 19110125
TI  - Detection of nicotine based on molecularly imprinted TiO2-modified electrodes.
AB  - Amperometric detection of nicotine (NIC) was carried out on a titanium dioxide
      (TiO(2))/poly(3,4-ethylenedioxythiophene) (PEDOT)-modified electrode by a
      molecular imprinting technique. In order to improve the conductivity of the
      substrate, PEDOT was coated onto the sintered electrode by in situ
      electrochemical polymerization of the monomer. The sensing potential of the NIC
      imprinted TiO(2) electrode (ITO/TiO(2)[NIC]/PEDOT) in a phosphate-buffered saline
      (PBS) solution (pH 7.4) containing 0.1M KCl was determined to be 0.88 V (vs.
      Ag/AgCl/saturated KCl). The linear detection range for NIC oxidation on the so
      called ITO/TiO(2)[NIC]/PEDOT electrode was 0-5mM, with a sensitivity and limit of
      detection of 31.35 microA mM(-1)cm(-2) and 4.9 microM, respectively. When
      comparing with the performance of the non-imprinted one, the sensitivity ratio
      was about 1.24. The sensitivity enhancement was attributed to the increase in the
      electroactive area of the imprinted electrode. The at-rest stability of the
      ITO/TiO(2)[NIC]/PEDOT electrode was tested over a period of 3 days. The current
      response remained about 85% of its initial value at the end of 2 days. The
      ITO/TiO(2)[NIC]/PEDOT electrode showed reasonably good selectivity in
      distinguishing NIC from its major interferent, (-)-cotinine (COT). Moreover,
      scanning electrochemical microscopy (SECM) was employed to elucidate the surface
      morphology of the imprinted and non-imprinted electrodes using Fe(CN)(6)(3
      )/Fe(CN)(6)(4-) as a redox probe on a platinum tip. The imprinted electrode was
      further characterized by scanning electron microscopy (SEM) and Fourier transform
      infrared spectroscopy (FTIR).

PMID- 19110126
TI  - Large volume injection for the direct analysis of ionophores and avermectins in
      surface water by liquid chromatography-electrospray ionization tandem mass
      spectrometry.
AB  - A simple method for the direct determination of residues of ionophore antibiotics
      and avermectin antiparasitics in surface water is reported. Using a large volume
      injector, a mixture of methanol and surface water is injected into an analytical
      liquid chromatography (LC) column and subsequently screened for residues of these
      veterinary pharmaceuticals using electrospray ionization tandem mass
      spectrometry. On-line sample enrichment and chromatographic separation are
      achieved using a single, short (20mm) octadecylsilane LC column. The method
      permits the detection of four ionophores and two avermectins in surface water
      samples at low ng L(-1) concentrations. Minimal matrix effects were observed for
      a variety of surface water samples which permitted the use of reagent-based
      standards for quantitation.

PMID- 19110127
TI  - Multiple compounds determination and fingerprint analysis of Lidanpaishi tablet
      and keli by high-performance liquid chromatography.
AB  - The objective of this paper was to establish an efficient method for quality
      control of Lidanpaishi (LDPS) tablet and keli, two famous traditional Chinese
      medicines. A simple and reliable high-performance liquid chromatography (HPLC)
      coupled with photodiode array detector (DAD) method was developed both for
      fingerprint analysis (FA) and quantitative determination. In quantitative
      analysis, linear regressions, limit of detection (LOD) and quantification (LOQ),
      intra-day and inter-day precisions, recovery, repeatability and stability were
      all tested and good results were obtained to simultaneously determine the 15
      marker compounds, namely chlorogenic acid, rhaponticin, 6,7-dimethoxycoumarin,
      naringin, hesperidin, neohesperidin, baicalin, wogonoside, baicalein, wogonin,
      chrysin, honokiol, magnolol, emodin, and chrysophanol in the herbal drugs. In
      fingerprint analysis, 34 peaks were selected as the characteristic peaks to
      evaluate the similarities of different samples collected from different
      pharmaceutical companies in China according to the State Food and Drug
      Administration (SFDA) requirements, and two kinds of data, relative retention
      time (RRT) and relative peak area (RPA) were used to identify the common peaks in
      15 samples for investigation. Furthermore, hierarchical cluster analysis (HCA)
      was also performed to evaluate the variation of the herbal drugs. The present
      approach, i.e. HPLC coupled with multiple compounds determination (MCD) and FA is
      a powerful and meaningful tool to comprehensively conduct the quality control of
      traditional Chinese medicines.

PMID- 19110128
TI  - Investigation into classification/sourcing of suspect counterfeit Heptodintrade
      mark tablets by near infrared chemical imaging.
AB  - Near infrared chemical imaging (NIR-CI) analysis was performed on 55 counterfeit
      Heptodin tablets obtained from a market survey and an additional 11 authentic
      Heptodin tablets for comparison. The aim of the study was to investigate whether
      NIR-CI can be used to detect the counterfeit tablets and to classify/source them
      so as to understand the possible number of origins to aid investigators and
      authorities to shut down counterfeiting operations. NIR-CI combined with
      multivariate analysis is particularly suited to compare chemical and physical
      properties of samples, since it is a quick and non-destructive method of
      analysis. Counterfeit tablets were easily distinguished from the authentic ones.
      Principal component analysis (PCA) and k-means clustering were performed on the
      data set. The results from both analyses grouped the counterfeit tablets in 13
      main groups. The main groups found with both methods were quite consistent. Out
      of the 55 tablets only 18% contained the correct active pharmaceutical ingredient
      (API), i.e., the anti-viral drug lamivudine. The remaining 82% of counterfeit
      tablets contained talc and starch as main excipients. The API containing tablets
      classified into three main groups, based mainly on the amount of lamivudine
      present in the tablet. The group which had close to the correct amount of
      lamivudine sub-classified into three groups. From the analysis carried out, it is
      likely that the counterfeit tablets originate from as many as 15 different
      sources.

PMID- 19110130
TI  - Epidemiology, risk factors, and consequences of obstructive sleep apnea and short
      sleep duration.
AB  - We will review the epidemiology, risk factors, and consequences of obstructive
      sleep apnea (OSA) and short/long sleep duration. Obstructive sleep apnea is a
      disease characterized by recurrent upper airway obstruction during sleep.
      Obstructive sleep apnea is common, with moderate to severe disease present in
      approximately 9% of middle aged men and 4% of women. The prevalence of OSA in
      certain patient populations (such as elderly patients, hypertensive patients,
      patients with coronary disease, and prebariatric surgery patients) is even
      greater. There are a number or risk factors for disease including obesity, male
      sex, and family history. Obstructive sleep apnea negatively impacts quality of
      life and is also associated with a number of adverse safety and health
      consequences including cardiovascular disease and motor vehicle crashes. Short
      habitual sleep duration can result in excessive daytime sleepiness and reduced
      neurocognitive function. Sleep loss may have long-term health consequences and
      may lead to premature death, cardiovascular disease, and the development of
      diabetes.

PMID- 19110129
TI  - Sleep and cardiovascular disease: an overview.

PMID- 19110131
TI  - Cardiovascular, inflammatory, and metabolic consequences of sleep deprivation.
AB  - That insufficient sleep is associated with poor attention and performance
      deficits is becoming widely recognized. Fewer people are aware that chronic sleep
      complaints in epidemiologic studies have also been associated with an increase in
      overall mortality and morbidity. This article summarizes findings of known
      effects of insufficient sleep on cardiovascular risk factors including blood
      pressure, glucose metabolism, hormonal regulation, and inflammation with
      particular emphasis on experimental sleep loss, using models of total and partial
      sleep deprivation, in healthy individuals who normally sleep in the range of 7 to
      8 hours and have no sleep disorders. These studies show that insufficient sleep
      alters established cardiovascular risk factors in a direction that is known to
      increase the risk of cardiac morbidity.

PMID- 19110132
TI  - Oxidative stress--a unifying paradigm in obstructive sleep apnea and
      comorbidities.
AB  - Obstructive sleep apnea (OSA), a highly prevalent breathing disorder in sleep,
      characterized by intermittent and recurrent pauses in respiration, has emerged as
      an independent risk factor for cardiovascular morbidity and mortality.
      Accumulated evidence implicates the apnea-related multiple cycles of
      hypoxia/reoxygenation in promoting the formation of reactive oxygen species and
      inducing oxidative stress. The ramifications of oxidative stress are pivotal;
      they can cause damage to biomolecules, and alter cellular functions, but they
      also function as signaling molecules in physiologic and pathophysiologic
      conditions. Oxidative stress alters signaling pathways and activates
      inflammatory/immune responses via increased interactions of blood cells with
      endothelial cells, facilitating endothelial cell injury and dysfunction. Such
      events can promote atherosclerosis and the development of cardiovascular
      morbidities in OSA. Oxidative stress is also a crucial component of obesity and
      metabolic disorders such as dyslipidemia and type 2 diabetes mellitus/insulin
      resistance, which cluster with OSA and involve inflammatory pathways as well.
      These converging lines of evidence point at oxidative stress as the unifying
      paradigm underlying the cardiovascular morbidity in OSA and very likely also in
      promoting the metabolic disorders associated. If left untreated, this cascade of
      events may eventually lead to overt cardiovascular morbidity.

PMID- 19110134
TI  - Sleep-disordered breathing: autonomic mechanisms and arrhythmias.
AB  - Obstructive sleep apnea (OSA) is present in at least 2% to 4% of the general
      population. Central sleep apnea (CSA), though less common, is highly prevalent in
      patients with heart failure. Both forms of sleep apnea exert strong modulatory
      effects on the autonomic nervous system at night through a number of mechanisms
      including central respiratory-cardiac coupling in the brainstem, chemoreflex
      stimulation, baroreflexes, and reflexes relating to lung inflation. Arousals also
      contribute to the autonomic disturbance. Although sleep is normally a time when
      parasympathetic modulation of the heart predominates and myocardial electrical
      stability is enhanced, OSA and CSA disturb this quiescence, creating an autonomic
      profile in which both profound vagal activity leading to bradyarrhythmias, and
      sympatho-excitation favoring ventricular ectopy are observed. The resulting
      tendency toward cardiac arrhythmia may directly contribute to sudden cardiac
      death and premature mortality in patients with sleep apnea. Therapy consists
      largely of treatment with continuous positive airway pressure, which has been
      shown to improve autonomic profile and reduce nocturnal arrhythmias.

PMID- 19110133
TI  - Mechanisms of apnea.
AB  - This paper focuses on the underlying mechanisms contributing to sleep-disordered
      breathing. Obstructive sleep apnea (OSA) is the most common sleep-related
      breathing disorder and is characterized by repetitive narrowing or collapse of
      the pharyngeal airway during sleep. Conversely, central sleep apnea (CSA), highly
      prevalent in congestive heart failure, is distinguished by a lack of drive to
      breathe during sleep, resulting in repetitive periods of insufficient
      ventilation. Both lead to compromised gas exchange, impaired sleep continuity,
      and catecholamine surges and are associated with major comorbidities including
      excessive daytime sleepiness and increased risk of cardiovascular disease.
      Although OSA and CSA exist on a spectrum of sleep-disordered breathing, the 2
      entities may overlap in their underlying pathophysiologies. This brief review
      summarizes the etiology and current understanding of OSA and CSA pathophysiology
      and the role that the cardiovascular system may play in contributing to disease
      pathology and highlights the likely substantial overlap that exists between the
      various forms of sleep-disordered breathing.

PMID- 19110135
TI  - Sleep in heart failure.
AB  - Sleep plays a large role in patients with heart failure. In normal subjects,
      sleep is usually in a supine position with reduced sympathetic drive, elevated
      vagal tone and as such a relatively lower cardiac output and minute ventilation,
      allowing for recuperation. Patients with heart failure may not experience the
      same degree of autonomic activity change and the supine position may place a
      large strain on the pulmonary system. More than half of all heart failure
      patients have one of two types of sleep apnea: either obstructive or central
      sleep apnea. Some patients have both types. Obstructive sleep apnea is likely to
      be a cause of heart failure due to large negative intrathoracic pressures, apnea
      related hypoxemia and hypercapnia, terminated by an arousal and surge in systemic
      blood pressure associated with endothelial damage and resultant premature
      atherosclerosis. Reversal of obstructive sleep apnea improves blood pressure,
      systolic contraction and autonomic dysfunction however mortality studies are
      lacking. Central sleep apnea with Cheyne Stokes pattern of respiration (CSA-CSR)
      occurs as a result of increased central controller (brainstem driving
      ventilation) and plant (ventilation driving CO2) gain in the setting of a delayed
      feed back (i.e., low cardiac output). It is thought this type of apnea is a
      result of moderately to severely impaired cardiac function and is possibly
      indicative of high mortality. Treatment of CSA-CSR is best undertaken by treating
      the underlying cardiac condition which may include with medications, pacemakers,
      transplantation or continuous positive airway pressure (CPAP). In such patients
      CPAP exerts unique effects to assist cardiac function and reduce pulmonary edema.
      Whether CPAP improves survival in this heart failure population remains to be
      determined.

PMID- 19110136
TI  - JVIR turns 20!

PMID- 19110137
TI  - Decompressive hemicraniectomy in large putaminal hematomas: an Indian experience.
AB  - OBJECTIVE: The treatment of large putaminal hematomas is predominantly medical
      and the role of surgery is debated. Decompressive hemicraniectomy in large
      hemispheric infarctions has been reported to lower mortality and improve
      outcomes. Decompressive hemicraniectomy may also have a role in putaminal
      hematomas. METHODS: In all, 23 patients with putaminal hematoma who underwent
      decompressive craniectomy in the last 4 years were analyzed. Parameters
      investigated included clinical presentations, radiologic profile, time interval
      from ictus to surgery, and Glasgow outcome score at 1 month. RESULTS: There were
      13 men and 10 women with ages ranging from 31 to 68 years. All of them presented
      with neurologic deficits. Seven patients had a Glasgow Coma Scale (GCS) score of
      3 to 8, 12 had a GCS score of 9 to 12, and GCS score was above 13 in 4. Seventeen
      patients had known hypertension. Computed tomography scan was done in all. The
      hematoma was less than 3 cm in 5 cases, 3 to 5 cm in 11, and larger than 5 cm in
      7; and was 30 mL or less in 3, 30 to 60 mL in 13, and more than 60 mL in 7. All
      patients underwent hemicraniectomy on the side of the lesion and dura was left
      open. At 3 months, 13 patients had a good outcome and 10 had a poor outcome
      (including 3 deaths). CONCLUSIONS: Decompressive hemicraniectomy can be a useful
      alternative surgical procedure in moderate to large putaminal hematomas.

PMID- 19110138
TI  - Stroke in Spain: epidemiologic incidence and patterns; a health sentinel network
      study.
AB  - INTRODUCTION: Cerebrovascular disease is among the 4 main causes of mortality in
      Spain. The objective of this study was to estimate the incidence of stroke and to
      describe the principal risk factors and other clinical and epidemiologic patterns
      found in patients. METHODS: Doctors from the Spanish sentinel health network
      recorded the episodes of acute cerebrovascular diseases in 2005 in a population
      of 201,205 inhabitants older than 14 years. The information of the patients (age
      and sex) and the episode (e.g., duration, symptoms, origin, medical attention,
      risk factors) was collected on a standard form. RESULTS: The estimated incidence
      rate of stroke was 141 cases per 100,000 inhabitants (confidence interval [CI]
      95%: 125-158), 134 (95% CI: 112-157) in women and 148 (95% CI: 124-172) in men.
      The incidence increases significantly from the age of 65 years and men younger
      than this have higher rates than women. In all, 12% of patients with stroke die
      within the first 24 hours. CONCLUSIONS: Incidence of cerebrovascular disease in
      Spain is below that recorded in other countries. There is no difference according
      to sex, but incidence among young and middle-aged men is greater than that among
      women. Significant variations from some population groups to others are observed,
      maybe because of the difference in the prevalence of risk factors.

PMID- 19110139
TI  - Thrombolytic treatment for stroke: patient preferences for treatment,
      information, and involvement.
AB  - BACKGROUND: Thrombolytic treatment for stroke carries the potential for a better
      functional outcome, but also a risk of intracranial hemorrhage and death.
      Ideally, the decision to treat should be based on the patient's preferences.
      METHODS: Study participants were 75 stroke survivors and 75 healthy, age-matched
      control subjects. We used the Standard Gamble method to elicit utility values for
      various stroke outcomes. We also assessed patients' preferences for: (1)
      thrombolytic treatment; (2) the format of information on effects of treatment;
      and (3) involvement in the decision-making process. RESULTS: Overall, the median
      utility values were 0.93 (interquartile range [IQR] 0.90-0.96) for a mild stroke,
      0.77 (IQR 0.65-0.85) for a moderately severe stroke, and 0.10 (IQR 0.05-0.20) for
      a severe stroke. Stroke survivors assigned significantly higher utility values
      than control subjects, as did participants older than 80 years and those who
      lived with a partner (P < .01). When participants were given the estimates of
      treatment effect and risk, 9% would have accepted thrombolytic treatment for a
      mild stroke, 87% for a moderately severe stroke, and 97% for a severe stroke. A
      majority of the participants (93%) wished to receive detailed information on
      risks and benefits of thrombolysis, and most (91%) preferred shared patient
      doctor decision-making. CONCLUSIONS: Preferences for thrombolytic treatment
      generally increase with increasing stroke severity, but individual factors, such
      as previous stroke, advanced age, and living conditions can influence the
      patient's decision. Most patients wanted precise information on the treatment's
      risks and benefits, and preferred to be actively involved in the decision-making
      process.

PMID- 19110140
TI  - Ancrod for acute ischemic stroke: a new dosing regimen derived from analysis of
      prior ancrod stroke studies.
AB  - BACKGROUND: Ancrod, a fibrinogen-reducing agent, has been evaluated as treatment
      beginning within 3 or 6 hours of onset of acute ischemic stroke with inconsistent
      results. The data sets from these studies provide an opportunity to determine
      whether ancrod-related variables are associated with efficacy and safety.
      OBJECTIVE: This post hoc analysis of data from the Stroke Treatment with Ancrod
      Trial (STAT) analyzed ancrod-related variables as potential determinants of
      efficacy or safety. The resulting hypotheses were then tested in the European
      STAT (ESTAT) database. METHODS: The relationships between ancrod-related
      variables and the outcomes of efficacy and symptomatic intracranial hemorrhage
      (ICH) were analyzed using a 3-stage multivariate process. RESULTS: Good clinical
      outcome at 3 months based on the Barthel Index occurred almost twice as often in
      rapid defibrinogenators (>or=30 mg/dL/h) (52%) as in slow defibrinogenators
      (26%), with no increase in mortality or symptomatic ICH. Compared with a 20.7%
      incidence of symptomatic ICH in patients with mean post-9-hour fibrinogen levels
      less than or equal to 60 mg/dL, symptomatic ICH incidence was 0.8% in those with
      mean levels greater than 60 mg/dL (with no loss of efficacy). There were no
      symptomatic ICHs among 220 North American patients with mean levels greater than
      70 mg/dL. It was hypothesized that an initial controlled rapid ancrod infusion
      with mean post-9-hour fibrinogen levels greater than 70 mg/dL would yield
      superior efficacy and safety. Such ESTAT patients had statistically significant
      efficacy versus placebo and a marked reduction in the incidence of symptomatic
      ICH versus patients taking ancrod with lower maintenance fibrinogen levels.
      CONCLUSION: Modifications to ancrod dosing may substantially improve efficacy
      while reducing the rate of symptomatic ICH.

PMID- 19110141
TI  - A case of unilateral thalamic hemorrhagic infarction as a result of the vein of
      Galen and straight sinus thrombosis.
AB  - Straight sinus vein thrombosis represents 15% of all diagnosed sinus vein
      thrombosis. Thrombotic occlusion of the deep cerebral venous system, the straight
      sinus, and the vein of Galen causes centrally located and usually bilateral
      thalamic infarcts. Unilateral thalamic venous infarction is extremely rare. The
      clinical and radiologic findings can be nonspecific and diagnostically
      challenging. We report a patient with this unusual condition and review the
      available literature.

PMID- 19110142
TI  - Cognitive consequences of multiple lacunes and leukoaraiosis as vascular
      cognitive impairment in community-dwelling elderly individuals.
AB  - The aim of our study was to investigate the effects of silent brain lesions on
      cognitive function of community-dwelling elderly individuals. Brain magnetic
      resonance imaging and other medical examinations were performed on 350
      nondemented elderly individuals (121 male and 229 female, average age 72.4 years)
      who resided in the rural community of Sefuri Village, Saga, Japan. The mini
      mental state examination and modified Stroop test (MST) were used to identify
      cognitive impairment. White matter lesions (WMLs) and cerebral atrophy on
      magnetic resonance imaging were measured quantitatively. Multivariate analyses
      were done using a logistic regression model with a software package. Cognitive
      impairment defined by mini mental state examination score less than 24 was
      present in 55 individuals (15.7%). They had a lower educational level,
      significantly larger quantity of WMLs, and more remarkable cerebral atrophy.
      Frontal lobe dysfunction was detected in 52 individuals (14.9%) through prolonged
      MST score (>36 seconds). Impaired frontal lobe function was related to number of
      silent lacunar infarcts, larger WMLs, and more prominent cerebral atrophy. MST
      score in individuals with two or more infarcts was significantly more prolonged
      compared with MST score in those without infarction. These results suggest that
      WMLs may cause rather diffuse cognitive decline, whereas multiple lacunar
      infarcts are specifically involved in frontal lobe dysfunction. Silent ischemic
      lesions in apparently healthy elderly individuals seem to form a distinctive
      group of people with vascular cognitive impairment without dementia. This group
      should be the primary target of prevention of vascular dementia.

PMID- 19110143
TI  - A care pathway to boost influenza vaccination rates among inpatients with acute
      ischemic stroke and transient ischemic attack.
AB  - BACKGROUND: Although influenza-related morbidity and mortality is high, and
      influenza can be a trigger for recurrent stroke, only about half of stroke
      survivors receive yearly influenza vaccination. Identifying new avenues through
      which to optimize influenza vaccination among stroke survivors is a public health
      need. We assessed the feasibility of integrating influenza vaccination into
      routine inpatient stroke care. METHODS: We designed a quality improvement project
      incorporating influenza vaccination into care administered to hospitalized
      patients with ischemic stroke and transient ischemic attack that included a
      standardized order and discharge checklist. Data were then prospectively
      collected on consecutively encountered patients with ischemic stroke and
      transient ischemic attack admitted to a university hospital stroke service during
      the influenza season of October 2007 to February 2008. Successful influenza
      treatment use was based on optimal rather than actual treatment, with credit for
      optimal treatment given if an acceptable reason for nonadministration of the
      vaccine was documented. RESULTS: Of 103 patients admitted during the study
      period, 75 (73%) were eligible for influenza vaccination (mean age 72.8 years;
      51% women). Among vaccination-eligible patients, 65 (87%) received optimal
      influenza vaccination treatment, whereas 14 (21%) actually received the
      vaccination during hospitalization. Leading reason (90%) for suboptimal influenza
      vaccination treatment among eligible patients was that the vaccination was
      inadvertently not ordered on admission or at discharge. CONCLUSIONS: Influenza
      vaccination can be systematically incorporated into stroke hospitalization and
      may be a viable avenue for promptly enhancing short-term clinical outcomes among
      hospitalized patients with stroke during peak influenza season.

PMID- 19110144
TI  - Neuroprosthesis for footdrop compared with an ankle-foot orthosis: effects on
      postural control during walking.
AB  - OBJECTIVES: We sought to compare the effects of a radio frequency-controlled
      neuroprosthesis on gait stability and symmetry to the effects obtained with a
      standard ankle-foot orthosis (AFO). METHODS: A total of 15 patients (mean age:
      52.2 +/- 3.6 years) with prior chronic hemiparesis resulting from stroke or
      traumatic brain injury (5.9 +/- 1.5 year) whose walking was impaired by footdrop
      and regularly used an AFO participated in the study. There was a 4-week
      adaptation period during which participants increased their daily use of the
      neuroprosthesis, while using the AFO for the rest of the day. Gait was then
      assessed in a 6-minute walk while wearing force-sensitive insoles, by using the
      neuroprosthesis and the AFO in a randomized order. An additional gait assessment
      was conducted after using the neuroprosthesis for a further 4 weeks. Gait speed
      and stride time (inverse of cadence) were determined, as were gait asymmetry
      index and swing time variability. RESULTS: After the 4-week adaptation period,
      there were no differences between walking with the neuroprosthesis and walking
      with the AFO (P > .05). After 8 weeks, there was no significant difference in
      gait speed, whereas stride time improved from 1.48 +/- 0.21 seconds with the AFO
      to 1.41 +/- 0.16 seconds with the neuroprosthesis (P < .02). Swing time
      variability decreased from 5.3 +/- 1.6% with the AFO to 4.3 +/- 1.4% with the
      neuroprosthesis (P = .01). A gait asymmetry index improved by 15%, from 0.20 +/-
      0.09 with the AFO to 0.17 +/- 0.08 with the neuroprosthesis (P < .05).
      CONCLUSIONS: Compared with AFO, the studied neuroprosthesis appears to enhance
      balance control during walking and, thus, more effectively manage footdrop.

PMID- 19110146
TI  - Percent change on the National Institutes of Health Stroke Scale: a useful acute
      stroke outcome measure.
AB  - BACKGROUND: A single optimal outcome measure in acute stroke has not been
      established. Changes in neurologic deficits might be useful outcome measures in
      acute stroke because they can measure within-subject changes on the entire
      spectrum of the scales starting at baseline. METHODS: We tested the ability of
      percent National Institutes of Health Stroke Scale (NIHSS) score change (baseline
      3 months) to predict the traditional functional outcomes in acute stroke
      (modified Rankin Scale [mRS], Barthel Index, Glasgow Outcome Scale, final NIHSS
      score). We analyzed data sets from two acute stroke clinical trials involving 44
      clinical research centers throughout the United States and 1899 randomized
      patients. RESULTS: The percent NIHSS score change predicted functional outcomes
      very well, all areas under the curve of 0.90 or greater with all P values less
      than .001 in receiver operating characteristic analysis. In the National
      Institute of Neurological Disorders and Stroke Recombinant Tissue Plasminogen
      Activator (rt-PA) Acute Stroke Trial, benefit from rt-PA was confirmed by a
      greater improvement on the NIHSS score than with placebo (67% v 50%, P < .002).
      In moderate stroke severity (baseline NIHSS score 7-15) an improvement of at
      least 55% was the best predictor of functional independence at 3 months (mRS <or=
      2). CONCLUSION: This novel approach to the NIHSS score as an outcome measure in
      acute stroke appears to be an additional useful analytic and communication tool.

PMID- 19110145
TI  - Aneurysmal subarachnoid hemorrhage in a Mexican multicenter registry of
      cerebrovascular disease: the RENAMEVASC study.
AB  - BACKGROUND: Information on risk factors and outcome of persons with aneurysmal
      subarachnoid hemorrhage (SAH) in Mexico is unknown. We sought to describe the
      clinical characteristics, risk factors, and outcome at discharge of Mexican
      patients with aneurysmal SAH. METHODS: A first-step surveillance system was
      conducted on consecutive cases confirmed by 4-vessel angiography from November
      2002 to October 2004 in 25 tertiary referral centers. Age- and sex-matched
      control subjects were randomly selected by a 1:1 factor, for multivariate
      analysis on risk factors. RESULTS: We studied 231 patients (66% women; mean age
      52 years, range 16-90 years). In 92%, the aneurysms were in the anterior
      circulation, and 15% had more than two aneurysms. After multivariate analysis,
      hypertension (odds ratio 2.46, 95% confidence interval 1.59-3.81) and diabetes
      mellitus (odds ratio 0.34, 95% confidence interval 0.17-0.68) were directly and
      inversely associated with aneurysmal SAH, respectively. Median hospital stay was
      23 days (range 2-98 days). Invasive treatment was performed in 159 (69%)
      patients: aneurysm clipping in 126 (79%), endovascular coiling in 29 (18%), and
      aneurysm wrapping in 4 (2%). The in-hospital mortality was 20% (mostly due to
      neurologic causes), and 25% of patients were discharged with a modified Rankin
      score of 4 or 5. CONCLUSIONS: Hypertension is the main risk factor for aneurysmal
      SAH in hospitalized patients from Mexico. The female:male ratio is 2:1. A
      relatively low in-hospital mortality and a high frequency of invasive
      interventions are observed. However, a high proportion of patients are discharged
      with important neurologic impairment.

PMID- 19110147
TI  - Locomotion outcome in hemiplegic patients with middle cerebral artery infarction:
      the difference between right- and left-sided lesions.
AB  - OBJECTIVE: This study was performed to analyze the locomotion outcome of
      hemiplegic patients with stroke and to explore the factors influencing it.
      METHODS: A total of 247 patients (mean age 65.6 +/- 10.5 years) admitted to our
      hospital for rehabilitation were included in the study. Their cardinal neurologic
      sign was hemiplegia caused by infarction in the middle cerebral artery as a
      result of a first stroke. When rehabilitation programs were completed, the final
      motor outcome was evaluated and compared between patients with right and left
      hemispheric infarct. In addition, the following items were analyzed: size,
      location, and subtype of the infarct; hemispatial neglect and aphasia; cerebral
      blood flow (CBF); and periventricular lucency on computed tomography scan.
      RESULTS: (1) There was a negative relationship between the infarct size and the
      locomotion outcome. The difference in locomotion outcome was not significant
      between the patients with infarction of the perforating arteries and those of the
      cortical arteries. No significant difference in the locomotion outcome was found
      between the patients with an atherothrombotic or cardioembolic infarction. (2) In
      spite of the existence of hemispatial neglect or aphasia, the patients with a
      right-sided infarction were significantly inferior to patients with a left-sided
      one in locomotion outcome, except for those with a large infarction. (3) In
      patients with infarction in the territory of the perforating arteries, there was
      a negative relationship between the area of decreased CBF or periventricular
      lucency and the locomotion outcome. When the area of decreased CBF on the
      homolateral hemisphere involving the infarction extended to less than or equal to
      two cerebral lobes, the locomotion outcome was significantly worse in the
      patients with a right-sided infarction. CONCLUSIONS: Overall, for the patients
      with middle cerebral artery infarction, the locomotion outcome was poorer in
      patients with a right hemispheric infarction than a left-sided one, except in the
      case of a large infarction.

PMID- 19110148
TI  - Sequential combination of two intravenous thrombolytics (recombinant tissue
      plasminogen activator/tenecteplase) in a patient with stroke and cardioembolic
      basilar artery occlusion.
AB  - Stroke caused by acute occlusion of basilar artery (AOBA) produces high risk of
      death. In eligible patients, thrombolysis significantly reduces mortality and
      disability rate. In most hospitals, thrombolysis is limited to intravenous (IV)
      route of recombinant tissue plasminogen activator, without any therapeutic
      alternative in cases of treatment failure. We report a case of cardioembolic
      AOBA, not responsive to a conventional regimen of IV recombinant tissue
      plasminogen activator. A sequential combination of IV tenecteplase (0.4 mg/kg)
      led to a complete recanalization of basilar artery, with a very good clinical
      outcome. The potential for a combination of two successive IV regimens should be
      evaluated in AOBA.

PMID- 19110149
TI  - The stroke that struck back: an unusual alien hand presentation.
AB  - Alien hand syndrome is a rare condition that can result from neurodegenerative
      disorders, tumors, or strokes. We encountered an acute presentation of alien hand
      syndrome from a right parietal ischemic stroke. The condition was not recognized
      by the emergency department, delaying diagnosis and appropriate treatment. Early
      recognition of unusual manifestations of stroke, such as an acute alien hand
      syndrome, can lead to timely diagnosis and therapy.

PMID- 19110150
TI  - Right internal carotid artery occlusion during intravenous thrombolysis for left
      middle cerebral artery occlusion.
AB  - Thrombolysis with recombinant tissue plasminogen activator is the only
      established treatment for acute ischemic stroke. Recurrent ischemic stroke
      involving an initially unaffected arterial territory during the course of
      thrombolysis has been reported but remains exceptionally rare. Here we report a
      75-year-old woman with acute left middle cerebral artery occlusion who developed
      right internal carotid artery occlusion during the last minutes of recombinant
      tissue plasminogen activator infusion. Although the transthoracic
      echocardiography did not reveal an intra-atrial thrombus, cardioembolism due to
      disintegration of a pre-existing thrombus was thought to be the underlying
      mechanism because the patient had atrial fibrillation. Arterial occlusion due to
      intraplaque hemorrhage and de novo thrombosis caused by thrombin-mediated
      platelet aggregation are also discussed as potential mechanisms of arterial
      occlusion.

PMID- 19110151
TI  - Keep the three hour TPA window: the lost study of Atlantis.

PMID- 19110152
TI  - Why fellowships?

PMID- 19110153
TI  - Immediate weight bearing following first metatarsophalangeal joint fusion with
      Kirschner wire fixation.
AB  - The general consensus regarding the postoperative management of patients who have
      undergone first metatarsophalangeal joint arthrodesis is to maintain non-weight
      bearing for 4 to 6 weeks. However, a number of studies indicate that immediate
      postoperative weight bearing does not result in a higher rate of nonunion. A
      retrospective case series investigation was performed to evaluate the fusion rate
      of first metatarsophalangeal joint arthrodesis using various forms of pin and
      wire fixation, and a postoperative protocol that involved immediate weight
      bearing with a padded surgical shoe. The impetus behind allowing immediate
      postoperative weight bearing stems from the desire to avoid difficult non-weight
      bearing forms of ambulation in patients at risk for falling, and to enhance
      postoperative rehabilitation in patients at risk for other joint maladies, as in
      those suffering with rheumatoid and other polyarticular forms of arthritis. A
      total of 22 fusions (20 patients) were reviewed. Nonunion developed in 2 feet
      (9.1%), and a delayed union occurred in 1 additional foot (4.55%), for a total
      complication rate of 13.64% (3/22 cases) and a fusion rate of 86.36%. The
      remaining patients demonstrated radiographic consolidation of the arthrodesis. A
      crude rough comparison to previously published reports, wherein weight bearing
      was initiated anywhere from immediately to up to 2 weeks postoperative, showed
      that the rate of fusion observed in the patients described in this report was
      similar. This study demonstrated that immediate ambulation following first
      metatarsophalangeal joint fusion with wire fixation was safe and effective. LEVEL
      OF CLINICAL EVIDENCE: 4.

PMID- 19110154
TI  - Bioabsorbable fixation for Mitchell's bunionectomy osteotomy.
AB  - Although bioabsorbable pins have been used to successfully stabilize a wide range
      of osteotomies, to date there have been not published studies describing the
      results of their use for fixation of first metatarsal osteotomies in Mitchell's
      bunionectomy. The purpose of this retrospective investigation of 78 first
      metatarsal osteotomies was to evaluate the effectiveness of polydioxanone
      bioabsorbable pin fixation of the first metatarsal osteotomy in Mitchell's
      bunionectomy. The mean length of the first metatarsal preoperatively was 6.65 +/-
      0.42 cm, and postoperatively it was 6.31 +/- 0.57 cm (P < .0001). The mean first
      IMA preoperatively was 17.59 degrees +/- 3.51 degrees , and postoperatively it
      was 9.91 degrees +/- 2.58 degrees (P < .0001). The mean HVA preoperatively was
      29.74 degrees +/- 4.70 degrees , and postoperatively it was 12.89 degrees +/-
      4.26 degrees (P < .0001). The average time to bony union was 6.01 +/- 0.61 weeks.
      There were 5 (6.41%) superficial wound infections that resolved with oral
      antibiotics, 1 (1.28%) deep-seated infection requiring surgical debridement, and
      2 (2.56%) patients complained of transfer metatarsalgia. Five (6.41%) patients
      displayed persistent localized translucency at some portion of the osteotomy site
      on postoperative radiographs, and there were no cases of progressive osteolysis.
      In this series there were no complications related to pin fracture or failure of
      osteotomy fixation. Based on the results observed in this study, it appears that
      the use of polydioxanone bioabsorbable pins provides satisfactory stabilization
      of the first metatarsal osteotomy in Mitchell's bunionectomy, and was not
      associated with any serious complications. LEVEL OF CLINICAL EVIDENCE: 2.

PMID- 19110155
TI  - Arthrodesis of the first metatarsocuneiform joint: a comparative cadaveric study
      of external and internal fixation.
AB  - Arthrodesis of the first metatarsocuneiform joint for the treatment of severe
      hallux abductovalgus with or without hypermobility of the first ray has gained
      popularity in recent years. The purpose of the current study was to compare the
      strength of external fixation to internal fixation for arthrodesis of the first
      metatarsocuneiform joint in a cadaveric model. Ten pairs of fresh frozen lower
      extremity cadaver specimens were used, and randomly assigned to fixation at the
      first metatarsocuneiform joint with crossed cannulated screws or a monorail
      uniplanar external fixator. Test specimens were then loaded to failure, which was
      defined as 3 mm or more of displacement at the arthrodesis site. Because of
      complications encountered during testing, 4 pairs of specimens were excluded from
      the final results. In the remaining 12 specimens (6 pairs of cadaver limbs), the
      mean maximal load to failure was 2300.02 +/- 711.86 N for the external fixator
      and 1666.38 +/- 1072.75 N for the internal fixation construct, and although this
      difference was not statistically significant (P = .2557), it was likely to have
      been clinically significant since approximately 27.55% more force was required to
      disrupt the external fixation construct in comparison with the internal fixation
      construct. Given these findings, further research into the mechanical and
      clinical properties of internal and external fixation for first
      metatarsocuneiform joint arthrodesis is warranted. LEVEL OF CLINICAL EVIDENCE: 5.

PMID- 19110156
TI  - The modified Mau-Reverdin double osteotomy for correction of hallux valgus: a
      retrospective study.
AB  - The deformity of hallux valgus is multifactorial, albeit primarily in the
      transverse plane. In order to achieve an anatomic correction, a surgical
      technique must be able to address the deformity with consistent outcomes. The
      purpose of the present study was to evaluate a technique designed to reposition
      the first metatarsal bone, metatarsophalangeal joint, and sesamoid apparatus in
      an anatomic and biomechanical corrected position for correction of hallux valgus
      deformity. This article is a retrospective analysis of 36 operations performed in
      28 individuals between January 1995 and December 2005. Each case involved the use
      of a modified-Mau osteotomy combined with a Reverdin osteotomy to correct the
      first intermetatarsal and proximal articular set angles. Comparisons were made
      between the preoperative and postoperative first IM angle, proximal articular set
      angle, tibial sesamoid position, and hallux valgus angle. The median follow-up
      period was 48 (range 12-121) months from the date of surgery. The median
      reduction of the 1-2 intermetatarsal angle was 12 degrees (range 5-19 degrees).
      The median decrease for the hallux valgus angle was 20.5 degrees (range 0-63
      degrees). The median reduction in the PASA was 16 degrees (range 4-69 degrees).
      The median decrease in the tibial sesamoid position was 5 (range 2-6). These
      differences were all highly statistically significant (P < .001), and all of the
      patients experienced a high rate of satisfaction (median AOFAS score 95 [range 70
      95]) following the intervention. The Mau-Reverdin double osteotomy appears to be
      an effective intervention for the radiographic and clinical correction of hallux
      valgus. LEVEL OF CLINICAL EVIDENCE: 4.

PMID- 19110157
TI  - A retrospective analysis of 50 consecutive Charcot diabetic salvage
      reconstructions.
AB  - Between January 2000 and May 2003, 50 consecutive Charcot diabetic salvage
      procedures were performed on 44 patients (average age 55.1 years). Twenty-four
      women (26 feet) and 20 men (24 feet) underwent a reconstructive limb salvage
      procedure for diabetic Charcot neuroarthropathy using a systematic surgical
      approach involving internal and external fixation. A retrospective analysis of
      patient satisfaction and clinical outcome was evaluated over a 2- to 5-year
      postoperative period; 75% of patients completed the SF-36 health survey and a
      patient satisfaction survey. A reliability analysis found the SF-36 survey to be
      an adequate health measurement tool in this Charcot neuroarthropathy cohort.
      Analysis of variance and categorical data analysis showed that the patients
      improved statistically significantly in response to surgical intervention;
      however, none of the demographic variables was statistically significantly
      associated with patient outcomes as measured by the SF-36 and the patient
      satisfaction survey. LEVEL OF CLINICAL EVIDENCE: 2.

PMID- 19110158
TI  - Combined clinical and laboratory testing improves diagnostic accuracy for
      osteomyelitis in the diabetic foot.
AB  - The purpose of this investigation was to examine the value of using routinely
      available clinical and laboratory tests in combination to distinguish
      osteomyelitis from cellulitis in a diabetic population with mild to moderately
      infected forefoot ulcers. We conducted a case-control study of 54 diabetic
      patients with 54 locally infected ulcers admitted to a university-affiliated
      tertiary-care hospital over a 4.5-year period. A total of 30 clinical and
      laboratory characteristics obtained at admission were tested for their
      association with pathology-proven osteomyelitis using logistic regression
      techniques. Ulcer depth greater than 3 mm (univariate odds ratio 10.4, P = .001)
      and C-reactive protein greater than 3.2 mg/dL (univariate odds ratio 10.8, P <
      .001) were the most informative individual clinical and laboratory tests for
      differentiating osteomyelitis from cellulitis. Adding C-reactive protein also
      significantly improved upon the accuracy of the study's best clinical testing
      strategy (area under the curve improved from 0.80 to 0.88, P = .040). Strategies
      that combined ulcer depth with serum inflammatory markers proved most useful in
      detecting ulcerated patients with concomitant bone infections (sensitivity 100%
      [95% CI 89.7%-100%] for both ulcer depth greater than 3 mm or C-reactive protein
      greater than 3.2 mg/dL, and ulcer depth greater than 3 mm or erythrocyte
      sedimentation rate greater than 60 mm/h). We conclude that considering clinical
      and laboratory findings together can significantly improve our diagnostic
      accuracy for osteomyelitis in the diabetic foot. The specific combination of
      ulcer depth with serum inflammatory markers appears to be a particularly
      sensitive strategy that may allow for greater detection of early diabetic
      osteomyelitis. LEVEL OF CLINICAL EVIDENCE: 3.

PMID- 19110159
TI  - Symptomatic medial exostosis of the great toe distal phalanx: a complication due
      to over-correction following akin osteotomy for hallux valgus repair.
AB  - The authors present the case of a 54-year-old female who developed a painful
      compression lesion localized to the medial aspect of the base of the distal
      phalanx of the great toe as a complication of hallux valgus surgery. Preoperative
      radiographic evaluation of the patient's foot revealed the first ray to be longer
      than the second, a 12 degrees first intermetatarsal angle, a 33 degrees hallux
      abductus angle, and an exostosis at the medial aspect of the base of the hallux
      that was not considered by the surgeon to be important. Correction of the hallux
      valgus deformity was performed with a combination of scarf and Akin osteotomies,
      and the intermetatarsal and hallux abductus angles reduced to 2 degrees and 8
      degrees , respectively. By 2 months postoperative, the patient was complaining of
      pain at the medial aspect of the distal phalanx of the hallux associated with
      shoe pressure. The pain correlated both clinically and radiologically with the
      exostosis at the base of the distal phalanx, and had become symptomatic only
      after the hallux had been operatively realigned. At 6 months postoperative,
      percutaneous exostectomy was undertaken to remove the exostosis. Pain relief was
      complete, thereafter, and after 2 years of postoperative follow-up the patient
      remained pain free. The clinical importance of a medial exostosis localized to
      the base of the distal phalanx of the hallux must be taken into consideration
      whenever hallux valgus correction is undertaken, and this is particularly
      important whenever an Akin osteotomy is being considered. LEVEL OF CLINICAL
      EVIDENCE: 4.

PMID- 19110160
TI  - Spinal cord stimulation in the treatment of complex regional pain syndrome (CRPS)
      of the lower extremity: a case report.
AB  - Complex regional pain syndrome (CRPS) is a condition that is often associated
      with the extremities. This chronic pain syndrome, when localized to the lower
      extremity, includes peripheral changes such as edema, temperature alterations,
      limited range of motion, loss of or excessive perspiration, pain out of
      proportion to any stimulus, and trophic alterations of the skin, hair, and nails.
      In this report, we describe the case of a patient who developed complex regional
      pain syndrome following an ankle injury and surgery. This case report highlights
      treatment options that are available to patients experiencing complex regional
      pain, including the use of a spinal cord stimulator. LEVEL OF CLINICAL EVIDENCE:
      4.

PMID- 19110161
TI  - Posterior tibial artery pseudoaneurysm identified subsequent to surgical wound
      dehiscence.
AB  - The development of a pseudoaneurysm of the posterior tibial artery is a rare
      event. In this article, we describe the case of a 63-year-old female with
      rheumatoid arthritis, who initially presented with a symptomatic subcutaneous
      nodule localized to the medial aspect of the right ankle. After excision of the
      subcutaneous nodule, she failed to heal the surgical wound and, eventually, the
      pseudoaneurysm of the posterior tibial artery was identified. It was not until
      after the posterior tibial artery was ligated and the pseudoaneurysm excised,
      that the wound finally healed. LEVEL OF CLINICAL EVIDENCE: 4.

PMID- 19110162
TI  - Reconstruction of the first metatarsophalangeal joint following post-cheilectomy
      avascular necrosis of the first metatarsal head: a case report.
AB  - Avascular necrosis of the first metatarsal head is a well-known, albeit rare,
      complication associated with hallux abductovalgus surgery. In this report, we
      describe the case of a 51-year-old male who developed osteonecrosis of the first
      metatarsal head 1 year after undergoing an isolated cheilectomy for the treatment
      of hallux rigidus. To our knowledge, this is the first published report of
      osteonecrosis following isolated cheilectomy used for the treatment of hallux
      rigidus. A bone graft substitute with undifferentiated stem cells was used to
      pack the medullary canals of the first metatarsal and the proximal phalanx. A
      section of autogenous calcaneal graft was used to perform a bone block
      distraction arthrodesis of the first metatarsophalangeal joint. LEVEL OF CLINICAL
      EVIDENCE: 4.

PMID- 19110163
TI  - Intra-osseous gout in a diabetic patient.
AB  - The following case is an interesting presentation of gout and its long-term
      affects in a diabetic individual. The patient initially presented with ankle pain
      and, after radiographic examination, a suspicious lytic lesion in the talus and a
      fracture of the medial malleolus were identified. A full workup with bone biopsy
      was undertaken and, although the patient did not present in the typical fashion,
      gout was ultimately diagnosed. Based on our experience with this patient, we
      recommend that gout be included in the list of differential diagnoses in diabetic
      patients with ankle pain and radiographic evidence of articular and bone
      destruction. The diagnosis and treatment of gout are addressed in this paper as
      well. LEVEL OF CLINICAL EVIDENCE: 4.

PMID- 19110164
TI  - A case of an aneurysmal bone cyst of a metatarsal: review of the differential
      diagnosis and treatment options.
AB  - Aneurysmal bone cyst localized to the metatarsus, while not unheard of, is rather
      uncommon. The differential diagnosis for this lesion can be challenging,
      particularly in regard to the possibility of the presence of other giant cells
      containing tumors of bone, such as giant cell tumor, giant cell reparative
      granuloma, Brown's tumor of hyperparathyroidism, and telangiectatic osteosarcoma.
      We report a case of an aneurysmal bone cyst localized to the third metatarsal in
      a 14-year-old girl who presented with limping, progressively worsening local
      pain, and swelling in her left foot. The differential diagnosis for her condition
      was extensive. Ultimately, an en bloc resection was undertaken and the defect was
      replaced with tricortical iliac autograft. Pathological analysis of the resected
      tissue was consistent with aneurysmal bone cyst. There was complete healing with
      no sign of recurrence 3 years after the surgery. LEVEL OF CLINICAL EVIDENCE: 4.

PMID- 19110165
TI  - Magnetic resonance imaging of a deep peroneal intraneural ganglion cyst
      originating from the second metatarsophalangeal joint: a pattern of propagation
      supporting the unified articular (synovial) theory for the formation of
      intraneural ganglia.
AB  - A deep peroneal intraneural cyst of the first web space of the foot is presented.
      Analysis of the magnetic resonance image scans revealed not only a connection
      with the medial aspect of the second metatarsophalangeal joint, but also the
      presence of an interconnected cyst within the lateral digital branch of the
      hallux. These characteristic magnetic resonance image findings are consistent
      with those previously described for a peroneal intraneural ganglion cyst that
      arose from the superior tibiofibular joint, and include (1) origin (ascent) from
      the second metatarsophalangeal joint with propagation along the articular branch
      and into the dorsal digital branch of the second toe, (2) cross-over within the
      shared epineurial sheath of the deep peroneal nerve, and (3) further propagation
      (descent) within the dorsal digital branch of the hallux. The analogous features
      between intraneural ganglion cysts affecting small and large-caliber nerves
      support the fundamental principles of the unified articular (synovial) theory for
      the formation of intraneural ganglia, including (1) a connection to a synovial
      joint, (2) dissection of joint fluid through a capsular rent along the articular
      branch into the parent nerve, and (3) intra-epineurial, pressure-dependent
      propagation of cyst fluid along paths of least resistance. LEVEL OF CLINICAL
      EVIDENCE: 4.

PMID- 19110166
TI  - A minimally invasive reduction and synthesis method for calcaneal fractures: the
      "Brixian bridge" technique.
AB  - Calcaneal fractures are difficult to treat because of their often-related
      sequelae. The authors present a simple, rapid, economic, and easy-to-perform
      technique that uses percutaneously positioned Kirschner wires plus a plaster cast
      for the reduction and stabilization of certain calcaneal fractures. A review of
      the relevant literature is also provided.

PMID- 19110167
TI  - Use of a small bilateral external fixator for ankle fusion.
AB  - A variety of methods are available for surgeons to use in an effort to achieve
      fusion ankle arthrodesis. Among these, external fixation devices have proven to
      be effective. In this article, we describe the use of a small external fixation
      frame that is affixed to the medial and lateral aspects of transfixation pins,
      and used to compress the arthrodesis interface.

PMID- 19110169
TI  - Abstracts of European Society for Clinical Virology (ESCV) Winter Meeting.
      Amsterdam, The Netherlands. January 7-10, 2009.

PMID- 19110168
TI  - The tripod fixation technique for ankle arthrodesis.
AB  - Fixation for ankle arthrodesis often consists of compression screws. A technique
      using a mechanically sound configuration for stable fixation is presented. The
      spatial orientation of the screws is in the form of a tripod that provides
      circumferential compression across the fusion mass. The sequence of delivery of
      the hardware minimizes the likelihood of intraosseous screw collision. The
      strategic placement of the screws also prevents stress concentration that may
      lead to stress risers in the distal tibia.

PMID- 19110178
TI  - Core competencies for gynecologic endoscopy in residency training: a national
      consensus project.
AB  - Residents and educators in obstetrics and gynecology have identified the need to
      improve endoscopic surgical education. The Canadian Endoscopy Education Project
      aims to create a national standardized endoscopy curriculum. The objective of the
      current project was to identify the core competencies for a gynecologic endoscopy
      (GE) curriculum in residency training programs. This expert consensus project
      (Canadian Task Force Classification III) included all 16 academic obstetrics and
      gynecology residency programs in Canada. Each university program selected their
      leading endoscopy educator to participate in the consensus process. Competencies
      for proficiency in GE were identified and then reviewed in 3 sequential rounds of
      consensus building using the Delphi technique. Overall, 213 objectives were
      reviewed and 199 (93%) of the items achieved consensus agreement. Competencies
      that were deemed outside the realm of general residency education were also
      collated and may represent a guide to subspecialty fellowship training in the
      future. The core competencies for GE training in obstetrics and gynecology
      residency were determined through national expert consensus. This provides the
      basis for a national standardized endoscopy curriculum for general obstetrics and
      gynecology training.

PMID- 19110180
TI  - Narrow band imaging in endometrial lesions.

PMID- 19110179
TI  - Laser carbon-dioxide treatment of complete hydatidiform mole presenting as
      Bartholin gland cyst.

PMID- 19110181
TI  - Unmet therapeutic needs for uterine myomas.
AB  - Uterine myomas may develop in many women, but only become clinically significant
      in about one third of the affected population. Although uterine myomas are most
      often benign, they are associated with debilitating symptoms and commonly result
      in hysterectomy. Current treatments for uterine myomas include pharmacologic
      therapies, delivery of focused energy, alteration of uterine vascular supply, or
      surgical procedures. Factors such as the woman's desire for future pregnancy, the
      importance of uterine preservation, symptom severity, and tumor characteristics
      direct the choice of therapeutic approach. The ideal treatment will have the
      following characteristics: easy to perform, minimally invasive, cost effective,
      preserves fertility, preserves the uterus, efficacious, acceptable tolerability
      and durability, and low incidence of myoma recurrence.

PMID- 19110182
TI  - Alexithymia-A disorder of the regulatory mechanism of the emotion elaboration-and
      quality of life in gynecologic surgery.
AB  - STUDY OBJECTIVE: Alexithymia is a disorder of the regulatory mechanism of the
      emotion elaboration. To verify the influence of the personality trait in the
      evaluation of quality of life (QoL), we analyzed the effect of alexithymia on the
      outcome of gynecologic surgery. The purpose of this study was to investigate the
      presence of alexithymia by using the Toronto Alexithymia Scale (TAS)-20, and to
      examine the relationship between alexithymia and self-reported descriptors of QoL
      in a gynecologic population. DESIGN: All patients were evaluated in a
      semistructured interview in which personal, medical, and social data were
      collected. They were provided with a set of questionnaires that included both
      measure of alexithymia (TAS-20) and QoL perception (the Medical Outcomes Study
      short-form general health survey-36 [SF-36]). The patients were assessed before
      the surgical procedure and 1 month postoperatively. SETTING: Campus BioMedico
      Hospital in Rome, Italy. PATIENTS: In all, 40 consecutive patients with benign
      gynecologic pathology were enrolled in the study. INTERVENTIONS: A total of 20 of
      the patients underwent laparoscopy (LPS) and 20 underwent laparotomy (LPT).
      MEASUREMENTS AND MAIN RESULTS: Patients were separated into 2 groups, with
      respect to the TAS questionnaire score: the high-level alexithymia (HA) group,
      with scores above 59, and the low-level alexithymia group, with scores below 59.
      The HA group represented 61% in patients who underwent LPS and 50% in patients
      who were submitted to LPT. Patients who underwent LPS showed a slight decrease in
      the QoL score after the surgical procedure. Patients who underwent LPT showed
      different QoL scores depending on the high or low TAS level: high-level TAS group
      showed higher SF-36 domain scores compared with the presurgical scores, whereas
      low-level TAS group showed lower scores compared with the presurgical scores.
      CONCLUSION: Our data show that the subjective QoL tested with SF-36 in patients
      with gynecologic conditions undergoing surgery is clearly influenced by the level
      of alexithymia. This influence is clearly detectable when a more invasive surgery
      is performed. In this case, patients with low-level alexithymia show a worsening
      of QoL. Contrarily, patients with HA have a better perception of QoL after more
      invasive surgery.

PMID- 19110183
TI  - Impact of laparoscopic experience on performance on laparoscopic training drills
      among obstetrics and gynecology residents: a pilot study.
AB  - STUDY OBJECTIVE: To assess whether volume of laparoscopic experience correlates
      with residents' performance on laparoscopic training drills. DESIGN: Residents
      performed 4 laparoscopic drills in the inanimate laboratory: peg transfer, bean
      drop, rope pass, and triangle transfer. Performance times were recorded.
      Laparoscopic experience as primary surgeon was determined from resident case
      logs. The resident data were divided according to volume of laparoscopic
      experience (0-19, 20-39, > or =40 cases). Performance times were compared among
      the groups according to volume of laparoscopic surgical experience. DESIGN
      CLASSIFICATION: II-3. SETTING: This study was conducted in a university school of
      medicine surgical skills laboratory. PARTICIPANTS: Participants in this study
      were obstetrics and gynecology residents entering their second through fourth
      years of training. INTERVENTIONS: Laparoscopic trainer drill performance times
      were recorded and correlated with amount of operative laparoscopic experience.
      MEASUREMENTS AND MAIN RESULTS: In all, 25 residents participated. Only the peg
      transfer drill showed statistically significant correlation between faster
      performance time and increasing laparoscopic experience (p =.01). No significant
      association existed between laparoscopic experience and performance time on the
      bean drop, triangle transfer, or rope pass drills. CONCLUSION: Residents with
      more laparoscopic experience performed the peg transfer drill significantly
      faster than those with less experience.

PMID- 19110184
TI  - Complete bladder gangrene caused by bilateral hypogastric artery ligation during
      laparoscopic radical hysterectomy.
AB  - Ischemic complications are extremely rare after radical pelvic surgery because of
      the collateral blood supply in the pelvis. We report a case of complete bladder
      gangrene 3 weeks after a laparoscopic radical hysterectomy with bilateral
      hypogastric artery ligation in a 70-year-old woman with cervical cancer.

PMID- 19110185
TI  - Beware the Tarlov cyst.
AB  - Tarlov cysts are sacral perineural cysts. This case report describes the clinical
      course after biopsy of a very large Tarlov cyst via laparoscopy, which was
      thought preoperatively to be an adnexal mass. It serves as a warning against
      attempting biopsy or resection of these lesions.

PMID- 19110186
TI  - Migration of an intrauterine contraceptive device during the course of pregnancy:
      a case report.
AB  - Uterine perforation by a contraceptive intrauterine device (IUD) is a relatively
      rare event. These events may result secondary to mechanical force applied during
      placement (primary perforation) or migration by uterine contractions or surgical
      manipulation after placement (secondary perforation). A 33-year-old woman with an
      IUD placed 9 years before admission visited the emergency department with an
      early pregnancy and a 3-day history of vaginal bleeding. Vaginal examination
      revealed IUD strings visible at the cervical os, and transvaginal ultrasound
      confirmed the presence of an IUD in the lower uterine segment and upper cervix.
      The IUD migrated spontaneously to the fundal myometrium at 15 weeks' gestation.
      Premature rupture of membranes ensued at 20 weeks' gestation, and, at delivery,
      the IUD could not be retrieved. Subsequent computed tomography confirmed that the
      IUD was incompletely embedded in the fundal myometrium and partially extending
      into the peritoneal cavity. At laparoscopic sterilization 6 weeks later, the IUD
      had perforated the small bowel, and the device was removed with concomitant bowel
      repair. This case documents spontaneous migration of a copper IUD from the lower
      uterine segment through the fundus during early pregnancy and supports removal of
      asymptomatic ectopic IUDs whenever possible.

PMID- 19110187
TI  - Recurrent thigh abscess with necrotizing fasciitis from a retained transobturator
      sling segment.
AB  - A woman who underwent transobturator sling surgery for urinary incontinence
      experienced early vaginal mesh erosion, and underwent a partial sling removal.
      Several months later, she developed recurrent right thigh and groin abscesses and
      necrotizing fasciitis. The source of the infection, a retained segment of mesh in
      the obturator space, was identified only after several operative procedures and
      referrals. This case illustrates several of the areas of concern with the
      introduction of new surgical materials and techniques.

PMID- 19110188
TI  - Hysteroscopic removal of gauze packing inadvertently sutured to the uterine
      cavity: report of 2 cases.
AB  - We report on 2 cases of successful hysteroscopic removal of uterovaginal packing,
      inserted during cesarean sections after uterine hemorrhage resistant to medical
      therapy. The packing, in both cases, could not be removed vaginally with sponge
      forceps because the packing had been sutured to the uterine cavity. A
      hysteroscopic approach enabled identification and cutting with 5F scissors of the
      stitches fixing the packing to the uterine walls, allowing straightforward
      removal in an outpatient setting and avoiding a repeated laparotomy. Some useful
      techniques to handle such a situation are described.

PMID- 19110189
TI  - Laparoscopic-assisted uterovaginal anastomosis for uterine cervix atresia with
      partial vaginal aplasia.
AB  - This case report describes the surgical technique of laparoscopic-assisted
      uterovaginal anastomosis. At a tertiary university hospital, a girl with uterine
      cervix atresia and vaginal aplasia underwent laparoscopic-assisted uterovaginal
      anastomosis. We assessed feasibility and anatomic outcome. The operating time was
      2 hours and 45 minutes. No perioperative or postoperative complications occurred.
      The hospital stay was 4 days. The surgical procedure resulted in adequate vaginal
      length (6 cm) and normal menstruation. Laparoscopic-assisted uterovaginal
      anastomosis without using a probe introduced by fundal incision is feasible with
      good anatomic results.

PMID- 19110190
TI  - Isolated extrapelvic endometriosis of the gluteal muscle.
AB  - A 33-year-old woman with a 2-year history of swelling and pain in her buttock and
      left thigh fluctuating with her menstrual cycle who was becoming progressively
      disabled was referred to the department of orthopedics. Magnetic resonance
      imaging (MRI) detected a left buttock lesion of 3 x 2 cm that was initially
      diagnosed as muscular-fiber laceration with associated hematoma. The worsening of
      her symptomatology required an ultrasound-guided biopsy of the lesion that
      revealed endometriosis. Laparoscopy showed the pelvis to be free of gross
      disease. Hormonal suppression by means of gonadotropin-releasing hormone analog
      therapy proved adequate in temporarily alleviating symptoms. A year later the
      patient underwent surgical excision of the buttock lesion, which was effective in
      alleviating her symptoms for a short period of 10 months. A 1-year follow-up MRI
      revealed several small endometriotic foci, located among piriformis and obturator
      internus muscle fibers, which were considered not suitable for surgical removal.
      The patient is currently on a drug regime for pain management. However, she has
      experienced permanent muscular damage on her left buttock including significant
      omolateral gluteus strength reduction, functional impairment (inability to rotate
      laterally or bend her left leg), and the assumption of an antalgic gait while
      walking. Because of impairment in her deambulation capability, total physical
      invalidity was agreed for her by the National Health Care Services.

PMID- 19110191
TI  - The sacral LION procedure for recovery of bladder/rectum/sexual functions in
      paraplegic patients after explantation of a previous Finetech-Brindley
      controller.
AB  - STUDY OBJECTIVE: To report on our technique of sacral laparoscopic implantation
      of aneuroprosthesis-LION procedure-for recovery of bladder/intestinal/sexual
      function in paralyzed patients after spinal cord injury. DESIGN: Prospective case
      series report. SETTING: Academic community teaching hospital. PATIENTS: Eight
      consecutive complete T-paralyzed patients after explantation of a previous dorsal
      implanted Brindley-Finetech controller with a sacral deafferentation.
      INTERVENTIONS: Laparoscopic transperitoneal exposure of the sacral plexuse and
      bilateral implantation of Brindley-Finetech electrodes to the sacral nerve roots
      S2 to S4. MEASUREMENTS AND MAIN RESULTS: Feasibility, complications, and outcome
      of the procedures. In 6 patients, recovery of electrically induced micturition
      and defecation could be obtained and in 2 men recovery of electrically induced
      erection. In 2 other patients, exposure and intraoperative stimulation of the
      sacral nerve roots showed irreversible destruction of the motoric vesical and
      rectal nerves. In one, the bilateral implantation of neuromodulation electrodes
      permitted complete control of the spasticity of the lower limbs and to the
      autonomic dysreflexia. CONCLUSION: The laparoscopic transperitoneal approach
      offers minimally invasive access for implantation of electrodes to the sacral
      nerve roots in paralyzed patients for recovery of pelvic visceral functions after
      failure of a previous implanted dorsal Brindley-Finetech controller with sacral
      deafferentation.

PMID- 19110192
TI  - Delayed iliac artery thrombosis after blunt trauma during operative laparoscopy.
AB  - Major vascular injury during laparoscopic surgery is an uncommon but serious
      complication. A small number of earlier case reports describe delayed diagnosis
      of vascular lacerations. Herein we report a unique case of a robot-assisted
      laparoscopic resection of an obstructed uterine horn, complicated by delayed
      postoperative presentation of a common iliac artery thrombus without
      extravascular hemorrhage. The injury was likely caused by blunt trauma to the
      exterior of the vessel with damage to the vascular intima and subsequent
      dissection. Meticulous surgical technique, accurate diagnosis, and subsequent
      treatment are essential to decrease morbidity from such major vascular injuries
      at the time of laparoscopy.

PMID- 19110193
TI  - Laparoscopic management of an isolated ovarian metastasis on a transposed ovary
      in a patient treated for stage IB1 adenocarcinoma of the cervix.
AB  - Transposition of the ovaries is performed frequently in young women with early
      stage cervical cancer. This procedure is performed to preserve their quality of
      life. However, this must be balanced with the risks of ovarian metastases
      especially in patients with adenocarcinomas. We report the first case of
      laparoscopic management of an isolated metastasis to a transposed ovary that
      occurred 2 years after primary laparoscopic treatment of a stage IB1
      adenocarcinoma of the cervix.

PMID- 19110194
TI  - Multifunctional drugs as neurotherapeutics.

PMID- 19110195
TI  - Multifunctional receptor-directed drugs for disorders of the central nervous
      system.
AB  - The marked decline in FDA-approved new drug candidates in recent years suggests
      the possibility that the "low-hanging fruit" has been almost entirely harvested.
      This might be particularly applicable to drugs acting on the central nervous
      system. Fortunately, there are several examples extant for the utility of
      multifunctional drugs, compounds, or drug mixtures that act on multiple additive
      or synergistic targets. However, to exploit this approach may require the
      willingness to consider the possibility that drug targets might be addressed by
      molecules of rather low specificity and moderate potency. The expectation is that
      single target molecules with high specificity might not have access to complex
      interacting neural pathways, and that moderate potency could engender fewer off
      target side effects. Though novel compounds might be developed by combining the
      active functional groups of two or more drug molecules, the approach still lends
      itself to high throughput screening of large chemical libraries. Multifunctional
      compounds might be designed with the ability to: 1) offer both palliative and
      disease modifying actions, 2) act on targets that produce additive or synergistic
      therapeutic responses, 3) simultaneously evoke a therapeutic response at the
      desired target and prevent an undesired response mediated by an alternate target,
      4) allow one component to promote the drugable characteristics (e.g., brain
      penetration) of the therapeutic component, and 5) prolong the duration of
      effectiveness of one compound by contributing the pharmacodynamic actions of
      another. The author takes the liberty to include examples of the situations just
      mentioned from studies in his laboratory in the following discussion.

PMID- 19110196
TI  - Multifunctional drug treatment in neurotrauma.
AB  - Although the concepts of secondary injury and neuroprotection after neurotrauma
      are experimentally well supported, clinical trials of neuroprotective agents in
      traumatic brain injury or spinal cord injury have been disappointing. Most
      strategies to date have used drugs directed toward a single pathophysiological
      mechanism that contributes to early necrotic cell death. Given these failures,
      recent research has increasingly focused on multifunctional (i.e.,
      multipotential, pluripotential) agents that target multiple injury mechanisms,
      particularly those that occur later after the insult. Here we review two such
      approaches that show particular promise in experimental neurotrauma: cell cycle
      inhibitors and small cyclized peptides. Both show extended therapeutic windows
      for treatment and appear to share at least one important target.

PMID- 19110197
TI  - Multifunctional drugs for head injury.
AB  - Traumatic brain injury (TBI) remains one of the leading causes of mortality and
      morbidity worldwide in individuals under the age of 45 years, and, despite
      extensive efforts to develop neuroprotective therapies, there has been no
      successful outcome in any trial of neuroprotection to date. In addition to
      recognizing that many TBI clinical trials have not been optimally designed to
      detect potential efficacy, the failures can be attributed largely to the fact
      that most of the therapies investigated have been targeted toward an individual
      injury factor. The contemporary view of TBI is that of a very heterogenous type
      of injury, one that varies widely in etiology, clinical presentation, severity,
      and pathophysiology. The mechanisms involved in neuronal cell death after TBI
      involve an interaction of acute and delayed anatomic, molecular, biochemical, and
      physiological events that are both complex and multifaceted. Accordingly,
      neuropharmacotherapies need to be targeted at the multiple injury factors that
      contribute to the secondary injury cascade, and, in so doing, maximize the
      likelihood of a successful outcome. This review focuses on a number of such
      multifunctional compounds that have shown considerable success in experimental
      studies and that show maximum promise for success in clinical trials.

PMID- 19110198
TI  - Multifunctional actions of approved and candidate stroke drugs.
AB  - Ischemic stroke causes brain damage by multiple pathways. Previous stroke trials
      have demonstrated that drugs targeting one or only a few of these pathways fail
      to improve clinical outcome after stroke. Drugs with multimodal actions have been
      suggested to overcome this challenge. In this review, we describe the mechanisms
      of action of agents approved for secondary prevention of ischemic stroke, such as
      antiplatelet, antihypertensive, and lipid-lowering drugs. These drugs exhibit
      considerable properties beyond their classical mechanisms, including
      neuroprotective and neuroregenerative properties. In addition, candidate stroke
      drugs currently studied in clinical phase III trials are described. Among these,
      albumin, hematopoietic growth factors, and citicoline have been identified as
      promising agents with multiple mechanisms. These drugs offer hope that additional
      treatment options for the acute phase after a stroke will become available in the
      near future.

PMID- 19110200
TI  - Building a better antipsychotic: receptor targets for the treatment of multiple
      symptom dimensions of schizophrenia.
AB  - Attempts to develop selective ("magic bullet") drugs for the treatment of
      schizophrenia have been frustrated by the complex etiology of the disease. The
      symptomatology of schizophrenia does not appear to arise from a single
      neurobiological entity, but rather may be derived from pathology at one or more
      receptor types. This has prompted multifactorial approaches to the development of
      new therapeutics, as embodied by polypharmacy and an alternative (or
      augmentative) strategy known as "intramolecular polypharmacy," in which a single
      drug possesses the capacity to affect multiple receptor types. Atypical
      antipsychotics are a well-known example of this approach; each atypical possesses
      a unique portfolio of activities at receptors that may contribute to therapeutic
      effects (as well as side effects). In this article we present a discussion of
      some of the receptor targets that are currently thought to mediate symptoms of
      schizophrenia, as well as their possible implications for the design of future
      multifunctional antipsychotics.

PMID- 19110199
TI  - Dual- and triple-acting agents for treating core and co-morbid symptoms of major
      depression: novel concepts, new drugs.
AB  - The past decade of efforts to find improved treatment for major depression has
      been dominated by genome-driven programs of rational drug discovery directed
      toward highly selective ligands for nonmonoaminergic agents. Selective drugs may
      prove beneficial for specific symptoms, for certain patient subpopulations, or
      both. However, network analyses of the brain and its dysfunction suggest that
      agents with multiple and complementary modes of action are more likely to show
      broad-based efficacy against core and comorbid symptoms of depression. Strategies
      for improved multitarget exploitation of monoaminergic mechanisms include triple
      inhibitors of dopamine, serotonin (5-HT) and noradrenaline reuptake, and drugs
      interfering with feedback actions of monoamines at inhibitory 5-HT(1A), 5-HT(1B)
      and possibly 5-HT(5A) and 5-HT(7) receptors. Specific subsets of postsynaptic 5
      HT receptors mediating antidepressant actions are under study (e.g., 5-HT(4) and
      5-HT(6)). Association of a clinically characterized antidepressant mechanism with
      a nonmonoaminergic component of activity is an attractive strategy. For example,
      agomelatine (a melatonin agonist/5-HT(2C) antagonist) has clinically proven
      activity in major depression. Dual neurokinin(1) antagonists/5-HT reuptake
      inhibitors (SRIs) and melanocortin(4) antagonists/SRIs should display advantages
      over their selective counterparts, and histamine H(3) antagonists/SRIs, GABA(B)
      antagonists/SRIs, glutamatergic/SRIs, and cholinergic agents/SRIs may counter the
      compromised cognitive function of depression. Finally, drugs that suppress 5-HT
      reuptake and blunt hypothalamo-pituitary-adrenocorticotrophic axis overdrive, or
      that act at intracellular proteins such as GSK-3beta, may abrogate the negative
      effects of chronic stress on mood and neuronal integrity. This review discusses
      the discovery and development of dual- and triple-acting antidepressants,
      focusing on novel concepts and new drugs disclosed over the last 2 to 3 years.

PMID- 19110201
TI  - Multifunctional pharmacotherapy: what can we learn from study of selective
      serotonin reuptake inhibitor augmentation of antipsychotics in negative-symptom
      schizophrenia?
AB  - Many patients suffering from major psychiatric disorders do not respond
      adequately to monotherapy and require additional drugs. To date, there are no
      objective guidelines for deciding which combination may be effective, and the
      choice is based on previous clinical experience and on trial and error. Even when
      combination drugs are effective, the biochemical mechanisms responsible for the
      value-added effect are unknown. Understanding the mechanism of such synergism may
      provide a rational basis for choosing drug combinations and for developing more
      effective drugs. In schizophrenia, negative symptoms respond poorly to
      antipsychotics, but may improve when these are augmented with selective serotonin
      reuptake inhibitors (SSRI). This augmenting effect cannot be explained by
      summating the pharmacological effects of the individual drugs. We proposed that
      the study of SSRI augmentation can serve as a window to understanding the
      biochemical mechanisms of clinically effective drug synergism. In a series of
      studies we identified unique biochemical effects of the combination, different
      from each individual drug, and proposed that some of these are involved in
      mediating the clinical effect. Here we review some of the findings and propose
      that the mechanism of action involves regionally selective modulation of the GABA
      system. The evidence indicates that the SSRI antidepressant-antipsychotic
      combination may be a useful paradigm for studying therapeutically effective
      synergistic drug interactions in schizophrenia. Although as yet limited in scope,
      the findings of definable molecular targets for synergistic SSRI-antipsychotic
      interaction provide new directions to inform future research and provide novel
      bio-molecular targets for drug development.

PMID- 19110202
TI  - Metabotropic glutamate receptors as targets for multipotential treatment of
      neurological disorders.
AB  - Glutamate is a major excitatory neurotransmitter in the CNS that is involved in
      numerous cellular functions, including cell death and survival. Metabotropic
      glutamate receptors (mGluR) are G-protein coupled receptors that have been
      classified into three groups on the basis of signal transduction pathways and
      pharmacological profiles. Group I, II, and III mGluRs are found on cell types
      within and peripheral to the CNS, including neurons, microglia, astrocytes,
      oligodendrocytes, T- and B-cell lymphocytes, osteoblasts, hepatocytes, and
      endothelial cells, among others. These receptors have a number of effects on
      cells that can influence outcome after trauma, including reducing neuronal and
      oligodendroglial cell death, inflammation, and endothelial permeability. Thus,
      mGluRs are a promising multipotential therapeutic approach. Because the pathology
      of CNS trauma and neurodegeneration is multifactorial (including, for example,
      oxidative stress, mitochondrial breakdown, and inflammation), therapies that
      serve to modulate multiple pathophysiological pathways may prove more effective
      than those directed at a single target. This review examines the multipotential
      therapeutic utility of mGluR modulation in acute and chronic injury and
      neurodegeneration.

PMID- 19110203
TI  - Therapeutic potential of erythropoietin and its structural or functional variants
      in the nervous system.
AB  - The growth factor erythropoietin (EPO) and erythropoietin receptors (EPOR) are
      expressed in the nervous system. Neuronal expression of EPO and EPOR peaks during
      brain development and is upregulated in the adult brain after injury.
      Peripherally administered EPO, and at least some of its variants, cross the blood
      brain barrier, stimulate neurogenesis, neuronal differentiation, and activate
      brain neurotrophic, anti-apoptotic, anti-oxidant and anti-inflammatory signaling.
      These mechanisms underlie their tissue protective effects in nervous system
      disorders. As the tissue protective functions of EPO can be separated from its
      stimulatory action on hematopoiesis, novel EPO derivatives and mimetics, such as
      asialo-EPO and carbamoylated EPO have been developed. While the therapeutic
      potential of the novel EPO derivatives continues to be characterized in
      preclinical studies, the experimental findings in support for the use of
      recombinant human (rh)EPO in human brain disease have already been translated to
      clinical studies in acute ischemic stroke, chronic schizophrenia, and chronic
      progressive multiple sclerosis. In this review article, we assess the studies on
      EPO and, in particular, on its structural or functional variants in experimental
      models of nervous system disorders, and we provide a short overview of the
      completed and ongoing clinical studies testing EPO as
      neuroprotective/neuroregenerative treatment option in neuropsychiatric disease.

PMID- 19110204
TI  - Biomarkers for evaluation of clinical efficacy of multipotential neuroprotective
      drugs for Alzheimer's and Parkinson's diseases.
AB  - During the last century, the world population has shown a staggering increase in
      its proportion of elderly members and thus neurodegenerative diseases like
      Alzheimer's disease (AD) and Parkinson's disease (PD), respectively, are becoming
      an increasing burden on society. Among the diverse, significant challenges facing
      clinicians, is the improvement of diagnostic measures to detect early and subtle
      symptoms, a phase in which prevention efforts might be expected to have their
      greatest impact and provide a measure of disease progression that can be
      evaluated during the course of drug treatment. At present, clinical diagnosis of
      AD and PD is based on a constellation of symptoms and manifestations, although
      the disease originated several years earlier. Given the multiple etiological
      nature of AD and PD, it is reasonable to assume that the initial causative
      pathobiological processes may differ between the affected individuals. Therefore,
      the availability of biological markers or biomarkers will help not only early
      disease diagnosis, but also delineate the pathological mechanisms more
      definitively and reliably than the traditional cognitive and neurological
      phenotypes. In the current article, we review the literature on biochemical,
      genetic, and neuroimaging biomarkers and discuss their predictive value as
      indicative for disease vulnerability to detect individuals at risk for PD and AD,
      and to determine the clinical efficacy of novel, disease-modifying
      (neuroprotective) strategies.

PMID- 19110206
TI  - Memoquin: a multi-target-directed ligand as an innovative therapeutic opportunity
      for Alzheimer's disease.
AB  - Alzheimer's disease is currently thought to be a complex, multifactorial
      syndrome, unlikely to arise from a single causal factor; instead, a number of
      related biological alterations are thought to contribute to its pathogenesis.
      This may explain why the currently available drugs, developed according to the
      classic drug discovery paradigm of "one-molecule-one-target," have turned out to
      be palliative. In light of this, drug combinations that can act at different
      levels of the neurotoxic cascade offer new avenues toward curing Alzheimer's and
      other neurodegenerative diseases. In parallel, a new strategy is emerging-that of
      developing a single chemical entity able to modulate multiple targets
      simultaneously. This has led to a new paradigm in medicinal chemistry, the "multi
      target-directed ligand" design strategy, which has already been successfully
      exploited at both academic and industrial levels. As a case study, we report here
      on memoquin, a new molecule developed following this strategy. The in vitro and
      in vivo biological profile of memoquin demonstrates the suitability of the new
      strategy for obtaining innovative drug candidates for the treatment of
      neurodegenerative diseases.

PMID- 19110205
TI  - Dual-target-directed drugs that block monoamine oxidase B and adenosine A(2A)
      receptors for Parkinson's disease.
AB  - Inadequacies of the current pharmacotherapies to treat Parkinson's disease (PD)
      have prompted efforts to identify novel drug targets. The adenosine A(2A)
      receptor is one such target. Antagonists of this receptor (A(2A) antagonists) are
      considered promising agents for the symptomatic treatment of PD. Evidence
      suggests that A(2A) antagonists may also have neuroprotective properties that may
      prevent the development of the dyskinesia that often complicates levodopa
      treatment. Because the therapeutic benefits of A(2A) antagonists are additive to
      that of dopamine replacement therapy, it may be possible to reduce the dose of
      the dopaminergic drugs and therefore the occurrence of side effects. Inhibitors
      of monoamine oxidase (MAO)-B also are considered useful tools for the treatment
      of PD. When used in combination with levodopa, inhibitors of MAO-B may enhance
      the elevation of dopamine levels after levodopa treatment, particularly when used
      in early stages of the disease when dopamine production may not be so severely
      compromised. Furthermore, MAO-B inhibitors may also possess neuroprotective
      properties in part by reducing the damaging effect of dopamine turnover in the
      brain. These effects of MAO-B inhibitors are especially relevant when considering
      that the brain shows an age-related increase in MAO-B activity. Based on these
      observations, dual-target-directed drugs, compounds that inhibit MAO-B and
      antagonize A(2A) receptors, may have value in the management of PD. This review
      summarizes recent efforts to develop such dual-acting drugs using caffeine as the
      lead compound.

PMID- 19110208
TI  - Polycyclic compounds: ideal drug scaffolds for the design of multiple mechanism
      drugs?
AB  - Recently there has been a resurging interest in developing multi-functional drugs
      to treat diseases with complex pathological mechanisms. Such drug molecules
      simultaneously target multiple etiologies that have been found to be important
      modulators in specific diseases. This approach has significant promise and may be
      more effective than using one compound specific for one drug target or, by a
      polypharmaceutical approach, using a cocktail of two or more drugs. Polycyclic
      ring structures are useful as starting scaffolds in medicinal chemistry programs
      to develop multi-functional drugs, and may also be useful moieties added to
      existing structures to improve the pharmacokinetic properties of drugs currently
      used in the clinic or under development. This review attempts to provide a
      synopsis of current published research to exemplify the use of polycyclic
      compounds as starting molecules to develop multi-functional drugs.

PMID- 19110207
TI  - Multifunctional neuroprotective derivatives of rasagiline as anti-Alzheimer's
      disease drugs.
AB  - The recent therapeutic approach in which drug candidates are designed to possess
      diverse pharmacological properties and act on multiple targets has stimulated the
      development of the multimodal drugs, ladostigil (TV3326) [(N-propargyl-(3R)
      aminoindan-5yl)-ethyl methyl carbamate] and the newly designed multifunctional
      antioxidant iron chelator, M-30 (5-[N-methyl-N-propargylaminomethyl]-8
      hydroxyquinoline). Ladostigil combines, in a single molecule, the
      neuroprotective/neurorestorative effects of the novel anti-Parkinsonian drug and
      selective monoamine oxidase (MAO)-B inhibitor, rasagiline (Azilect, Teva
      Pharmaceutical Co.) with the cholinesterase (ChE) inhibitory activity of
      rivastigmine. A second derivative of rasagiline, M-30 was developed by
      amalgamating the propargyl moiety of rasagiline into the skeleton of our novel
      brain permeable neuroprotective iron chelator, VK-28. Preclinical experiments
      showed that both compounds have anti-Alzheimer's disease activities and thus, the
      clinical development is oriented toward treatment of this type of dementia. This
      review discusses the multimodal effects of two rasagiline-containing hybrid
      molecules, namely ladostigil and M-30, concerning their neuroprotective molecular
      mechanisms in vivo and in vitro, including regulation of amyloid precursor
      protein processing, activation of protein kinase C, and mitogen-activated protein
      kinase signaling pathways, inhibition of cell death markers and upregulation of
      neurotrophic factors. Altogether, these scientific findings make these
      multifunctional compounds potentially valuable drugs for the treatment of
      Alzheimer's disease.

PMID- 19110209
TI  - Novel anti-Alzheimer's dimer Bis(7)-cognitin: cellular and molecular mechanisms
      of neuroprotection through multiple targets.
AB  - Alzheimer's disease (AD) is a progressive and degenerative brain disorder that
      has emerged as one of the major public health problems in adults. Unfortunately,
      its molecular pathology and therapeutic strategies remain elusive. Because there
      are multiple factors closely indicated in the pathogenesis of AD, multiple drug
      therapy will be required to address the varied pathological aspects of this
      disease. Existing pharmacological approaches with one-molecule-one-target are
      limited in their ability to modify the pathology of AD. Novel therapeutics
      strategies comprise multifunctional compounds specifically designed to target
      concurrently on different sites at multifactorial etiopathogenesis of AD, thereby
      providing greater therapeutic efficacy. Over the past decade, our group has
      developed several series of dimeric acetylcholinesterase (AChE) inhibitors
      derived from tacrine and huperzine A, a unique anti-Alzheimer's drug originally
      discovered from a traditional Chinese medicinal plant. Bis(7)-Cognitin, one of
      our novel dimers, through inhibition of AChE, N-methyl-D-aspartate receptor,
      nitric oxide synthase, and amyloid precursor protein/beta-amyloid cascade
      concurrently, possesses remarkable neuroprotective activities. More importantly,
      the synergism between these targets might serve as one of the most effective
      therapeutic strategies to arrest/modify pathological process of AD in addition to
      improving the cognitive functions for AD.

PMID- 19110210
TI  - The effect of perchlorate ions on a pyridine-based microgel.
AB  - The effect of perchlorate ions as counterions in the acid-induced swelling of
      poly(2-vinylpyridine) microgel particles was investigated. The pH was modified
      with perchloric, hydrochloric and hydrobromic acids and the particle diameter
      measured using dynamic light scattering and the viscosity monitored using a
      capillary viscometer. The microgel particles were found to have a lower apparent
      pK(a) with perchloric acid, 4.10 compared to 4.70 with hydrochloric and
      hydrobromic acids. As a result the particles swell at a lower pH and they also
      swell to a lower maximum diameter with perchloric acid, 681+/-8 nm compared to
      751+/-15 nm for hydrochloric and hydrobromic acids. The swelling transition is
      also continuous with perchloric acid, whereas it has been identified as first
      order with hydrochloric acid. Similar variations were found in the viscosity
      using the different acids. The differences can be accounted for by the
      dehydrating and cross-linking nature of the perchlorate ion.

PMID- 19110211
TI  - A genome-wide association study identifies three loci associated with mean
      platelet volume.
AB  - Mean platelet volume (MPV) is increased in myocardial and cerebral infarction and
      is an independent and strong predictor for postevent morbidity and mortality. We
      conducted a genome-wide association study (GWAS), the KORA (Kooperative
      Gesundheitsforschung in der Region Augsburg) F3 500K study, and found MPV to be
      strongly associated with three common single-nucleotide polymorphisms (SNPs):
      rs7961894 located within intron 3 of WDR66 on chromosome 12q24.31, rs12485738
      upstream of the ARHGEF3 on chromosome 3p13-p21, and rs2138852 located upstream of
      TAOK1 on chromosome 17q11.2. We replicated all three SNPs in another GWAS from
      the UK and in two population-based samples from Germany. In a combined analysis
      including 10,048 subjects, the SNPs had p values of 7.24 x 10(-48) for rs7961894,
      3.81 x 10(-27) for rs12485738, and 7.19 x 10(-28) for rs2138852. These three
      quantitative trait loci together accounted for 4%-5% of the variance in MPV. In
      depth sequence analysis of WDR66 in 382 samples from the extremes revealed 20 new
      variants and a haplotype with three coding SNPs and one SNP at the transcription
      start site associated with MPV (p = 6.8 x 10(-5)). In addition, expression
      analysis indicated a direct correlation of WDR66 transcripts and MPV. These
      findings may not only enhance our understanding of platelet activation and
      function, but may also provide a focus for several novel research avenues.

PMID- 19110212
TI  - Mutations in DDR2 gene cause SMED with short limbs and abnormal calcifications.
AB  - The spondylo-meta-epiphyseal dysplasia [SMED] short limb-hand type [SMED-SL] is a
      rare autosomal-recessive disease, first reported by Borochowitz et al. in
      1993.(1) Since then, 14 affected patients have been reported.(2-5) We diagnosed 6
      patients from 5 different consanguineous Arab Muslim families from the Jerusalem
      area with SMED-SL. Additionally, we studied two patients from Algerian and
      Pakistani ancestry and the parents of the first Jewish patients reported.(1)
      Using a homozygosity mapping strategy, we located a candidate region on
      chromosome 1q23 spanning 2.4 Mb. The position of the Discoidin Domain Receptor 2
      (DDR2) gene within the candidate region and the similarity of the ddr2 knockout
      mouse to the SMED patients' phenotype prompted us to study this gene(6). We
      identified three missense mutations c.2254 C > T [R752C], c. 2177 T > G [I726R],
      c.2138C > T [T713I] and one splice site mutation [IVS17+1g > a] in the conserved
      sequence encoding the tyrosine kinase domain of the DDR2 gene. The results of
      this study will permit an accurate early prenatal diagnosis and carrier screening
      for families at risk.

PMID- 19110213
TI  - Mutations of the SYCP3 gene in women with recurrent pregnancy loss.
AB  - Aneuploidy, a chromosomal numerical abnormality in the conceptus or fetus, occurs
      in at least 5% of all pregnancies and is the leading cause of early pregnancy
      loss in humans. Accumulating evidence now suggests that the correct segregation
      of chromosomes is affected by events occurring in prophase during meiosis I.
      These events include homologous chromosome pairing, sister-chromatid cohesion,
      and meiotic recombination. In our current study, we show that mutations in SYCP3,
      a gene encoding an essential component of the synaptonemal complex that is
      central to the interaction of homologous chromosomes, are associated with
      recurrent pregnancy loss. Two out of 26 women with recurrent pregnancy loss of
      unknown cause were found to carry independent heterozygous nucleotide alterations
      in this gene, neither of which was present among a group of 150 fertile women.
      Analysis of transcripts from minigenes harboring each of these two mutations
      revealed that both affected normal splicing, possibly resulting in the production
      of C-terminally mutated proteins. The mutant proteins were found to interact with
      their wild-type counterpart in vitro and inhibit the normal fiber formation of
      the SYCP3 protein when coexpressed in a heterologous system. These data suggest
      that these mutations are likely to generate an aberrant synaptonemal complex in a
      dominant-negative manner and contribute to abnormal chromosomal behavior that
      might lead to recurrent miscarriage. Combined with the fact that similar
      mutations have been previously identified in two males with azoospermia, our
      current data suggest that sexual dimorphism in response to meiotic disruption
      occurs even in humans.

PMID- 19110214
TI  - A recessive skeletal dysplasia, SEMD aggrecan type, results from a missense
      mutation affecting the C-type lectin domain of aggrecan.
AB  - Analysis of a nuclear family with three affected offspring identified an
      autosomal-recessive form of spondyloepimetaphyseal dysplasia characterized by
      severe short stature and a unique constellation of radiographic findings.
      Homozygosity for a haplotype that was identical by descent between two of the
      affected individuals identified a locus for the disease gene within a 17.4 Mb
      interval on chromosome 15, a region containing 296 genes. These genes were
      assessed and ranked by cartilage selectivity with whole-genome microarray data,
      revealing only two genes, encoding aggrecan and chondroitin sulfate proteoglycan
      4, that were selectively expressed in cartilage. Sequence analysis of aggrecan
      complementary DNA from an affected individual revealed homozygosity for a
      missense mutation (c.6799G --> A) that predicts a p.D2267N amino acid
      substitution in the C-type lectin domain within the G3 domain of aggrecan. The
      D2267 residue is predicted to coordinate binding of a calcium ion, which
      influences the conformational binding loops of the C-type lectin domain that
      mediate interactions with tenascins and other extracellular-matrix proteins.
      Expression of the normal and mutant G3 domains in mammalian cells showed that the
      mutation created a functional N-glycosylation site but did not adversely affect
      protein trafficking and secretion. Surface-plasmon-resonance studies showed that
      the mutation influenced the binding and kinetics of the interactions between the
      aggrecan G3 domain and tenascin-C. These findings identify an autosomal-recessive
      skeletal dysplasia and a significant role for the aggrecan C-type lectin domain
      in regulating endochondral ossification and, thereby, height.

PMID- 19110215
TI  - The diagnostic dilemma of thrombotic thrombocytopenic purpura/hemolytic uremic
      syndrome in the obstetric triage and emergency department: lessons from 4
      tertiary hospitals.
AB  - OBJECTIVE: We report a series of occurrences of thrombotic thrombocytopenic
      purpura (TTP)/hemolytic uremic syndrome (HUS) in pregnancy that emphasizes early
      diagnosis. STUDY DESIGN: Fourteen pregnancies with TTP (n = 12) or HUS (n = 2)
      were studied. Analysis focused on clinical and laboratory findings on
      examination, initial diagnosis, and treatment. RESULTS: There were 14 pregnancies
      in 12 patients; 2 cases of TTP were diagnosed as recurrent. Five women were
      admitted to the emergency department (ED), and 7 patients were admitted to an
      obstetrics triage. Patients who were evaluated by an obstetrician were treated
      initially for hemolysis, elevated liver enzymes and low platelets
      syndrome/preeclampsia, whereas patients who were seen in the ED had a diagnosis
      that is commonplace in the ED (panic attack, domestic violence, gastroenteritis).
      Latency from the onset of symptoms to diagnosis ranged from 1-7 days.
      Plasmapheresis treatments in early gestation resulted in favorable maternal
      neonatal outcome. Maternal and perinatal mortality rates were 25% each.
      CONCLUSION: TTP/HUS is a challenging diagnosis in obstetric triage and ED areas.
      We propose a management scheme that suggests how to triage patients for early
      diagnosis in pregnancy.

PMID- 19110217
TI  - Coffee drinking and endometrial cancer risk: a metaanalysis of observational
      studies.
AB  - We conducted a metaanalysis of published studies on the relation between coffee
      drinking and endometrial cancer risk, which included 2 cohort (201 cases) and 7
      case-control studies (2409 cases). The summary relative risk (RR) for coffee
      drinkers vs nondrinkers was 0.80 (95% confidence interval [CI], 0.68-0.94), with
      significant heterogeneity between studies. Compared with nondrinkers, the summary
      RR was 0.87 (95% CI, 0.78-0.97) for low-to-moderate coffee drinkers and 0.64 (95%
      CI, 0.48-0.86) for heavy coffee drinkers. The summary RR for an increase of 1
      cup/d was 0.93 (95% CI, 0.89-0.97), which suggests an inverse relation between
      coffee and endometrial cancer. However, the causality must be confirmed.

PMID- 19110216
TI  - Correlation of glucose concentrations in maternal serum and amniotic fluid in
      high-risk pregnancies.
AB  - OBJECTIVE: We sought to determine whether a correlation exists between maternal
      serum glucose and amniotic fluid glucose in high-risk pregnancies. STUDY DESIGN:
      We conducted a prospective cross-sectional study of 60 patients, between 15 and
      38 weeks' gestation, undergoing amniocentesis between March 2006 and April 2007.
      Participants underwent amniocentesis with evaluation of amniotic fluid glucose
      and maternal finger stick glucose. Data were collected on maternal demographics,
      gestational age, presence of diabetes or chorioamnionitis, use of betamethasone,
      and body mass index. Statistical analyses included Spearman rho correlations.
      RESULTS: A positive correlation was found between maternal serum glucose and
      amniotic fluid glucose (r = 0.401, P < .01), and amniotic fluid index and
      diabetes (r = 0.367, P < .05). An inverse correlation was found between amniotic
      fluid glucose and chorioamnionitis (r = -0.499, P < .01). CONCLUSION: Maternal
      hyperglycemia directly influences amniotic fluid glucose levels and may result in
      an elevated amniotic fluid glucose value.

PMID- 19110218
TI  - Symptomatic pelvic organ prolapse and possible risk factors in a general
      population.
AB  - OBJECTIVE: We sought to examine the prevalence of pelvic organ prolapse (POP)
      symptoms and risk factors in a general white population. STUDY DESIGN: This was a
      cross-sectional study. All female residents aged 45-85 years in a small Dutch
      city received validated questionnaires. Women were classified as symptomatic if
      they reported feeling and/or seeing vaginal bulge. RESULTS: Response rate was
      62.7% (1869/2979). Prevalence of POP was 11.4%. Multivariate analysis revealed
      POP symptoms during pregnancy, a maternal history of POP, and heavy physical
      work, with a total population-attributable risk of 46%. CONCLUSION: There is high
      prevalence of symptomatic POP in a general white population of which independent
      risk factors are POP symptoms during pregnancy, a maternal history of POP, and
      heavy physical work. Clinicians should focus on risk factors in counseling of
      (pregnant) women to inform women to be aware of further exposures for themselves
      and their daughters.

PMID- 19110219
TI  - Carboplatin and paclitaxel adjuvant chemotherapy in primitive neuroectodermal
      tumor of the uterine corpus.
AB  - Primitive neuroectodermal tumor of the uterine corpus (PNET) is rare and appears
      to have an aggressive clinical course. We report on a postmenopausal woman with
      optimal surgically cytoreduced advanced-stage PNET in which adjuvant combination
      chemotherapy with platinum and taxane agents was unsuccessful in extending her
      disease-free survival.

PMID- 19110220
TI  - Physical activity and obesity in endometrial cancer survivors: associations with
      pain, fatigue, and physical functioning.
AB  - OBJECTIVE: This study aims to determine the prevalence of physical activity and
      obesity and their relationship to physical functioning (PF), fatigue, and pain in
      endometrial cancer survivors. STUDY DESIGN: Surveys were mailed to 200 survivors
      of endometrial cancer diagnosed within the last 5 years; 61% were returned.
      Surveys assessed physical activity, height and weight, comorbid health problems,
      PF, fatigue, and pain. RESULTS: In all, 22% exercised in the past month at the
      level of current public health recommendations, 41% reported no physical
      activity, and 38% reported some activity. A total of 16% were overweight and 50%
      were obese. Both lower body mass index (BMI) and higher physical activity were
      related to better PF. Higher physical activity was related to less fatigue,
      primarily for patients of normal BMI. CONCLUSION: Results suggest endometrial
      cancer survivors' obesity and inactivity contributes to poorer quality of life.
      This population could benefit from quality-of-life interventions incorporating
      physical activity.

PMID- 19110221
TI  - Relationship of obesity to outcome of medical abortion.
AB  - OBJECTIVE: The purpose of this study was to compare the outcome of medical
      abortion for obese women and nonobese women. STUDY DESIGN: We conducted a chart
      review of women having medical abortions in 2005-2007. Outcomes were classified
      as surgical intervention, need for additional visits, and complete abortion. The
      rate of surgical intervention was compared for women with BMI less than 30 to
      women with BMI greater than 30. RESULTS: Of the 1202 eligible procedures using
      mifepristone and misoprostol, there were 861 women with BMI less than 30 and 341
      women with BMI greater than 30. Women with BMI less than 30, and women with BMI
      greater than 30 had identical rates of surgical intervention, 5% and 6%,
      respectively (P = .72). CONCLUSION: In light of the additional risks of surgical
      abortion to obese women, medical abortion should be considered for these women.

PMID- 19110222
TI  - Hyperhomocysteinemia is not sufficient to cause preeclampsia in an animal model:
      the importance of folate intake.
AB  - OBJECTIVE: The objective of our study was to determine whether
      methylenetetrahydrofolate reductase (Mthfr)-deficient mice develop preeclampsia
      (PE). STUDY DESIGN: Mice were placed on a normal or low-folate/high-methionine
      (LF/HM) diet to assess the impact of mild and severe homocysteinemia. Blood
      pressure and proteinuria were measured throughout gestation in Mthfr-deficient
      and control mice on both diets, by radiotelemetry and by determining the urinary
      albumin/creatinine ratio by enzyme-linked immunosorbent assay, respectively.
      RESULTS: Although Mthfr-deficient mice have endothelial dysfunction, they do not
      develop hypertension or proteinuria during gestation. The LF/HM diet induced
      proteinuria, growth restriction, and a decrease in the number of pups per litter
      in all mice without any effect on the placenta. CONCLUSION: Our study clearly
      demonstrates that hyperhomocysteinemia is not sufficient to cause PE in this
      animal model. Furthermore, it confirms the importance of folate intake on
      pregnancy outcomes.

PMID- 19110224
TI  - A double-blind, randomly assigned, placebo-controlled study of desvenlafaxine
      efficacy and safety for the treatment of vasomotor symptoms associated with
      menopause.
AB  - OBJECTIVE: The objective of the study was to assess the efficacy and safety of
      desvenlafaxine (administered as desvenlafaxine succinate) for menopausal
      vasomotor symptoms. STUDY DESIGN: Postmenopausal women (n = 458) experiencing 50
      or more moderate to severe hot flushes per week received desvenlafaxine 100 or
      150 mg/d, with titration at therapy initiation, or placebo. Hot flush number and
      severity were assessed at weeks 4 and 12. Safety data were collected throughout
      the trial. RESULTS: Desvenlafaxine 100 and 150 mg/d significantly reduced the
      number of hot flushes compared with placebo at weeks 4 and 12 (all P < or =
      .012), achieving 65.4% and 66.6% reductions from baseline at week 12,
      respectively (placebo, 50.8%). Hot flush severity and number of nighttime
      awakenings were significantly reduced at both time points (all P < or = .048).
      Desvenlafaxine groups reported significantly more adverse events compared with
      placebo during week 1 only. No difference in discontinuations because of adverse
      events was observed. CONCLUSION: Desvenlafaxine is an effective nonhormonal
      treatment for menopausal hot flushes. Dose titration improves initial
      tolerability.

PMID- 19110223
TI  - Duration of lactation and incidence of myocardial infarction in middle to late
      adulthood.
AB  - OBJECTIVE: We assessed the relation between duration of lactation and maternal
      incident myocardial infarction. STUDY DESIGN: This was a prospective cohort study
      of 89,326 parous women in the Nurses' Health Study. RESULTS: During 1,350,965
      person-years of follow-up, 2540 cases of coronary heart disease were diagnosed.
      Compared with parous women who had never breastfed, women who had breastfed for a
      lifetime total of 2 years or longer had 37% lower risk of coronary heart disease
      (95% confidence interval, 23-49%; P for trend < .001), adjusting for age, parity,
      and stillbirth history. With additional adjustment for early-adult adiposity,
      parental history, and lifestyle factors, women who had breastfed for a lifetime
      total of 2 years or longer had a 23% lower risk of coronary heart disease (95%
      confidence interval, 6-38%; P for trend = .02) than women who had never
      breastfed. CONCLUSION: In a large, prospective cohort, long duration of lactation
      was associated with a reduced risk of coronary heart disease.

PMID- 19110225
TI  - Neonatal and maternal outcomes associated with elective term delivery.
AB  - OBJECTIVE: To quantify adverse neonatal and maternal outcomes associated with
      elective term delivery at less than 39 completed weeks of gestation. STUDY
      DESIGN: Prospective observational study conducted in 27 hospitals over the course
      of 3 months in 2007. RESULTS: Of 17,794 deliveries, 14,955 (84%) occurred at 37
      weeks or greater. Of term deliveries, 6562 (44%) were planned, rather than
      spontaneous. Among the planned deliveries, 4645 (71%) were purely elective; 17.8%
      of infants delivered electively without medical indication at 37-38 weeks and 8%
      of those delivered electively at 38-39 weeks required admission to a newborn
      special care unit for an average of 4.5 days, compared with 4.6% of infants
      delivered at 39 weeks or beyond (P < .001). Cesarean delivery rate in women
      undergoing induction of labor was not influenced by gestational age but was
      highly influenced by initial cervical dilatation and parity, ranging from 0% for
      parous women induced at 5 cm or greater to 50% for nulliparous women at 0 cm.
      CONCLUSION: Elective delivery before 39 weeks' gestation is associated with
      significant neonatal morbidity. Initial cervical dilatation is highly correlated
      with cesarean delivery among women undergoing induction of labor in both
      nulliparous and parous women. Elective delivery before 39 completed weeks'
      gestation is inappropriate. Women contemplating elective induction at or beyond
      39 weeks' gestation with an unfavorable cervix should be counseled regarding an
      increased rate of cesarean delivery.

PMID- 19110226
TI  - Abnormal fetal heart rate tracing patterns in patients with thick meconium
      staining of the amniotic fluid: association with perinatal outcomes.
AB  - OBJECTIVE: The objective of the study was to evaluate, in labors complicated by
      thick meconium-stained amniotic fluid, the association between specific fetal
      heart rate (FHR) patterns and adverse perinatal outcomes. STUDY DESIGN: A
      retrospective cohort study of patients with FHR tracing data (n = 1638) from a
      previously reported randomized controlled trial of amnioinfusion for the
      prevention of meconium aspiration syndrome. RESULTS: The presence of FHR tracing
      abnormalities was associated with an increased risk of perinatal mortality and/or
      neonatal morbidity (moderately abnormal: adjusted odds ratio [OR], 1.67; 95%
      confidence interval [CI], 1.18-2.37; markedly abnormal: adjusted OR, 2.97; 95%
      CI, 1.88-4.67). Specific abnormalities that were associated with the risk of
      perinatal mortality and/or neonatal morbidity included prolonged decelerations
      (OR, 1.22; 95% CI, 1.02-1.48), severe variable decelerations (OR, 1.08; 95% CI,
      1.00-1.16), bradycardia (OR, 2.49; 95% CI, 1.02-6.11), and tachycardia (OR, 2.43;
      95% CI, 1.49-3.94). CONCLUSION: The presence of abnormal FHR tracing patterns in
      meconium-stained amniotic fluid patients is associated with an increased risk of
      adverse perinatal outcomes.

PMID- 19110227
TI  - Gelsolin down-regulates lipopolysaccharide-induced intraamniotic tumor necrosis
      factor-alpha production in the midtrimester of pregnancy.
AB  - OBJECTIVE: The purpose of this study was to identify gelsolin in midtrimester
      amniotic fluid and evaluate its interaction with lipopolysaccharide (LPS). STUDY
      DESIGN: Supernatants from 40 midtrimester amniotic fluid samples were incubated
      with Escherichia coli LPS, and gelsolin binding was measured by enzyme-linked
      immunosorbent assay. Unfractionated aliquots of 25 of the fluids were cultured ex
      vivo for 24 hours in the presence of LPS and supernatants tested for tumor
      necrosis factor (TNF)-alpha and interleukin (IL)-10 production, and the influence
      of antigelsolin antibody was evaluated. RESULTS: Each amniotic fluid was positive
      for gelsolin that bound to LPS. LPS-induced TNF-alpha production was inversely
      proportional to the amniotic fluid concentrations of LPS-bound gelsolin (r = 
      0.5047; P = .006). Preincubation with monoclonal antibody to gelsolin led to an
      increase in LPS-induced TNF-alpha production (P = .01). There was no relationship
      between gelsolin and IL-10 production. CONCLUSION: Gelsolin is present in
      midtrimester amniotic fluid, binds to LPS, and inhibits the induction of TNF
      alpha.

PMID- 19110228
TI  - A comparison of younger vs older women with vulvar cancer in the United States.
AB  - OBJECTIVE: The purpose of this study was to compare the prognostic variables and
      survival of younger (< 50 years) to that of older (> or = 50 years) women with
      vulvar cancer. STUDY DESIGN: Subjects with invasive squamous cell carcinoma of
      the vulva were identified from the limited use Surveillance, Epidemiology, and
      End Results (SEER) Program 1988-2005. Comparisons between younger and older women
      were accomplished with chi(2) and t-tests. Survival analysis was accomplished
      with Kaplan-Meier for univariate analysis and Cox proportional hazards model for
      multivariate analysis. RESULTS: A total of 6965 patients met inclusion criteria,
      of whom 1345 patients (19.3%) were younger and 5620 patients (80.7%) were older.
      The 5-year survival was 87.5% for younger women and 52.5% for older women (P <
      .001). After data were controlled for race, stage, grade, and surgical treatment,
      older patients had a hazard ratio of 3.9 (95% CI, 3.2-4.7) for death. CONCLUSION:
      A striking survival difference exists between younger and older women with
      squamous cell vulvar cancer, which supports the view that etiopathogenesis of
      this disease may vary between age groups.

PMID- 19110229
TI  - Delayed-interval delivery in twin and triplet pregnancies: 17 years of experience
      in 1 perinatal center.
AB  - OBJECTIVE: There are few prospective cohorts of delayed-interval delivery for
      twin and triplet pregnancies. Nonetheless, the procedure is an option to improve
      perinatal outcome. STUDY DESIGN: A standard protocol was designed before
      candidates for delayed interval were managed by the 2 authors from 1991 to 2007.
      Perinatal as maternal outcomes were evaluated up to 1 year. RESULTS: In 93 twin
      and 34 triplet pregnancies, the inclusion criteria were fulfilled; in 45 twin and
      8 triplet pregnancies, there were contraindications to prolong pregnancy; and in
      10 twin and 26 triplet pregnancies, asynchronous delivery was not possible
      because of immediate delivery of the remaining multiples. Thus, the procedure was
      performed in only 41% (38/93) of twin and 35% (12/34) of triplet pregnancies
      admitted with threatening early delivery. Among twin pregnancies, the mean delay
      was 19 (1-107) days. When the first delivery was less than 25 weeks, no first
      twin but 9 of 18 second twins (50%) survived (P < .001). Survival rate of first
      twins born beyond 25 weeks was 13 of 20 (65%) compared with 19 of 20 (95%) (P =
      .03) in corresponding second twins. In 7 of 12 triplet pregnancies with the first
      born less than 25 weeks, 2 of 14 remaining triplets survived after an interval of
      118 days. Beyond 25 weeks, 3 of 5 first and 4 of 10 remaining triplets survived
      after intervals of 2-13 days (P = n.s.). Delay between second and third triplet
      was never longer than 2 days. Frequent maternal complications were
      chorioamnionitis (22%), postpartum hemorrhage, retained placenta (10%), and
      abruption (6%). CONCLUSION: Our study provides data to assist physicians in the
      informed consent process when asynchronous delivery is considered and feasible.

PMID- 19110230
TI  - Robotic-assisted laparoscopic cerclage in a pregnant patient.
AB  - A robotic-assisted laparoscopic technique for transabdominal cerclage placement
      could offer improvements over the traditional laparoscopic approach. A gravid
      female with no vaginal portion of the cervix underwent a robotic-assisted
      laparoscopic cerclage at 12 weeks' gestation and ultimately delivered a healthy
      infant at term.

PMID- 19110231
TI  - Alterations in phosphorylated cyclic adenosine monophosphate response element of
      binding protein activity: a pathway for fetal alcohol syndrome-related
      neurotoxicity.
AB  - OBJECTIVE: Fetal alcohol syndrome (FAS) is the leading cause of a spectrum of
      preventable nongenetic learning and behavioral disorders. In adult (FAS) mice, we
      measured phosphorylated cyclic adenosine monophosphate response element of
      binding protein (pCREB) staining in hippocampal subregions to evaluate a possible
      mechanism underlying FAS learning deficits. STUDY DESIGN: Pregnant C57BL6/J mice
      were treated on gestational day 8 with alcohol or control (saline). After
      learning assessment, the offspring were perfused for immunohistochemistry and
      brain sections probed using SER 133 pCREB antibody. Relative staining density was
      assessed using National Institutes of Health Image software. Statistical analysis
      included analysis of variance with P < .05 considered significant. RESULTS: In
      all hippocampal subregions, pCREB staining was greater in the control animals
      than in the alcohol-treated group (P < or = .0001). CONCLUSION: In utero alcohol
      exposure decreased pCREB activity in hippocampal subregions of adult mice. The
      dentate gyrus had the most robust cumulative decrease in pCREB staining,
      suggesting FAS adult learning deficits may correlate to enhanced dentate gyrus
      neurodegeneration.

PMID- 19110232
TI  - Fetal magnetic resonance imaging in isolated diaphragmatic hernia: volume of
      herniated liver and neonatal outcome.
AB  - OBJECTIVE: We sought to use magnetic resonance (MR) imaging (MRI) to estimate
      percentage of fetal thorax occupied by lung, liver, and other abdominal organs in
      pregnancies with congenital diaphragmatic hernia (CDH). STUDY DESIGN: This was a
      retrospective study of pregnancies with isolated CDH referred for MRI between
      August 2000 and June 2006. Four regions of interest were measured in the axial
      plane by an investigator blinded to neonatal outcome, and volumes were then
      calculated. The percentages of thorax occupied by lung, liver, and all herniated
      organs were then compared with neonatal outcomes. RESULTS: Fifteen CDH fetuses
      underwent MRI at a median gestational age of 29 weeks. Liver herniation was found
      in 93%. When the liver occupied > 20% of the fetal thorax, neonatal deaths were
      significantly increased. Percentages of lung and other herniated organs were not
      associated with outcome. CONCLUSION: In our MR series of isolated CDH, neonatal
      deaths were significantly increased when > 20% of the fetal thorax was occupied
      by liver.

PMID- 19110233
TI  - Intravenous lipopolysaccharide-induced pulmonary maturation and structural
      changes in fetal sheep.
AB  - BACKGROUND: Antenatal pulmonary inflammation is associated with reduced risk for
      respiratory distress syndrome but with an increased risk for bronchopulmonary
      dysplasia (BPD) with impaired alveogenesis. OBJECTIVE: We hypothesized that fetal
      systemic inflammation induced by intravenous (IV) lipopolysaccharide (LPS) would
      affect lung development in utero. STUDY DESIGN: Twenty-one fetal sheep were
      instrumented (107 days gestational age). Control fetuses received saline (N = 12)
      and 9 in the study group received 100 ng of LPS IV 3 days after surgery. Animals
      were assessed for lung maturation and structure after 3 (N = 5) and 7 (N = 4)
      days. RESULTS: Interleukin-6 concentration increased in the bronchoalveolar
      lavage more than 40-fold 3 days after LPS IV. Processing of pro-surfactant
      protein (SP)-B to mature SP-B and increased SP-B concentrations were shown 7 days
      after LPS IV. Deposition of elastin fibers at sites of septation was disturbed
      within 3 days after LPS IV. CONCLUSION: Lung maturation and disturbed lung
      structure occurred after short-term exposure to fetal inflammation and suggests
      new targeted therapies for BPD.

PMID- 19110234
TI  - Azacitidine enhances sensitivity of platinum-resistant ovarian cancer cells to
      carboplatin through induction of apoptosis.
AB  - OBJECTIVE: The objective of the study was to investigate whether azacitidine
      sensitizes platinum-resistant ovarian cancer cells to carboplatin and the
      possible mechanisms involved. STUDY DESIGN: We tested the in vitro antitumor
      activity of azacitidine both alone and combined with carboplatin in the ovarian
      cancer cell line 2008/C13 and Hey by 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2H
      tetrazolium bromide assays and investigated the potential mechanisms by flow
      cytometry, terminal transferase deoxyuridine 5-triphosphate nick-end labeling
      assay, Western blot, reverse transcriptase-polymerase chain reaction (PCR), and
      promoter methylation-specific PCR. RESULTS: Sequential treatment (ie, 24-hour
      azacitidine pretreatment followed by 48-hour cotreatment with azacitidine and
      carboplatin) significantly inhibited growth in 2008/C13 and Hey cells. More
      apoptotic cells were induced in 2008/C13 cells by sequential treatment than by a
      single drug. Increased cleaved caspase-3 and -8 were seen in 2008/C13 cells after
      sequential treatment with azacitidine and carboplatin. DR4 was demethylated, and
      DR4 messenger ribonucleic acid expression was increased in 2008/C13 cells after
      the 24-hour azacitidine treatment. CONCLUSION: Azacitidine enhanced the
      sensitivity of platinum-resistant ovarian cancer cells to carboplatin associated
      with caspase-3- and -8-dependent apoptosis pathway and reexpression of DR4.

PMID- 19110235
TI  - Vitamin C intake inhibits serum lipid peroxidation and osteoclast differentiation
      on alveolar bone in rats fed on a high-cholesterol diet.
AB  - OBJECTIVE: A high-cholesterol diet stimulates osteoclast differentiation, which
      may be induced by increased serum lipid peroxidation. The inhibition of serum
      lipid peroxidation by vitamin C may offer beneficial effects on osteoclast
      differentiation including increased expression of receptor activator of nuclear
      factor (NF)-kappaB ligand (RANKL) and NF-kappaB. This study investigated the
      effects of vitamin C intake on RANKL and NF-kappaB expression in periodontal
      tissue of rats fed a high-cholesterol diet. DESIGN: Twenty-four rats (8 weeks
      old) were divided into four groups: a control group (fed a regular diet) and
      three experimental groups (fed a high-cholesterol diet supplemented with 0, 1 and
      2 g/l vitamin C/day) in this 12-week study. Vitamin C was provided by its
      addition to drinking water. As an index of serum lipid peroxidation, hexanoyl
      lysine (HEL) level was determined by a competitive enzyme-linked immunosorbent
      assay method. Immunohistological analysis was performed to evaluate RANKL and NF
      kappaB expression on the alveolar bone surface. The number of tartrate-resistant
      acid phosphatase (TRAP)-positive osteoclasts was also counted. RESULTS: Feeding a
      high-cholesterol diet increased not only the serum HEL level but also the number
      of TRAP-positive osteoclasts on the alveolar bone surface, with an increase in
      RANKL and NF-kappaB expression on alveolar bone surface. Intake of vitamin C
      reduced the serum HEL level and osteoclast differentiation, with decreasing RANKL
      and NF-kappaB expression. CONCLUSIONS: Vitamin C intake could suppress osteoclast
      differentiation, including RANKL and NF-kappaB expression on the alveolar bone
      surface, by decreasing serum lipid peroxidation in rats fed a high-cholesterol
      diet.

PMID- 19110236
TI  - Cognitive Triad Inventory (CTI): psychometric properties and factor structure of
      the German translation.
AB  - A central component of Beck, A. T., Rush, J., & Shaw, B. F. [(1979). Cognitive
      therapy of depression. New York: Guilford Press] cognitive theory of depression
      is the cognitive triad (negative view of self, world, and future) measurable with
      the Cognitive Triad Inventory (CTI). This study examined the psychometric
      properties and factor structure of the German CTI in a sample of 796 German
      volunteers. The study provides evidence for the reliability and validity of the
      German CTI and of independent positive and negative elements of the cognitive
      triad. Furthermore, results emphasize methodological above conceptual problems in
      Beck et al.'s (1979) theory as cause for instabilities in the CTI's factor
      structure across different studies.

PMID- 19110237
TI  - Efficient synthesis of jusbetonin, an indolo[3,2-b]quinoline glycoside, and its
      derivatives.
AB  - Jusbetonin, an indolo[3,2-b]quinoline alkaloid glycoside originally isolated from
      Justicia betonica, and its derivatives were synthesized. The key steps in the
      synthetic strategy were the construction of indolo[3,2-b]quinoline skeleton and
      efficient coupling with the saccharides, in which the alpha-D-glycopyranosyl
      bromides were shown to be effective donors. Primary screening showed that all
      synthesized compounds possessed moderate proliferation inhibitory activity.

PMID- 19110238
TI  - Articulatory mediation of speech perception: a causal analysis of multi-modal
      imaging data.
AB  - The inherent confound between the organization of articulation and the acoustic
      phonetic structure of the speech signal makes it exceptionally difficult to
      evaluate the competing claims of motor and acoustic-phonetic accounts of how
      listeners recognize coarticulated speech. Here we use Granger causation analyzes
      of high spatiotemporal resolution neural activation data derived from the
      integration of magnetic resonance imaging, magnetoencephalography and
      electroencephalography, to examine the role of lexical and articulatory mediation
      in listeners' ability to use phonetic context to compensate for place
      assimilation. Listeners heard two-word phrases such as pen pad and then saw two
      pictures, from which they had to select the one that depicted the phrase.
      Assimilation, lexical competitor environment and the phonological validity of
      assimilation context were all manipulated. Behavioral data showed an effect of
      context on the interpretation of assimilated segments. Analysis of 40 Hz gamma
      phase locking patterns identified a large distributed neural network including 16
      distinct regions of interest (ROIs) spanning portions of both hemispheres in the
      first 200 ms of post-assimilation context. Granger analyzes of individual
      conditions showed differing patterns of causal interaction between ROIs during
      this interval, with hypothesized lexical and articulatory structures and pathways
      driving phonetic activation in the posterior superior temporal gyrus in
      assimilation conditions, but not in phonetically unambiguous conditions. These
      results lend strong support for the motor theory of speech perception, and
      clarify the role of lexical mediation in the phonetic processing of assimilated
      speech.

PMID- 19110239
TI  - Qualitative differences in the representation of abstract versus concrete words:
      evidence from the visual-world paradigm.
AB  - In the present visual-world experiment, participants were presented with visual
      displays that included a target item that was a semantic associate of an abstract
      or a concrete word. This manipulation allowed us to test a basic prediction
      derived from the qualitatively different representational framework that supports
      the view of different organizational principles for concrete and abstract words
      in semantic memory. Our results confirm the assumption of a primary
      organizational principle based on association for abstract words, different from
      the semantic similarity principle proposed for concrete words, and provide the
      first piece of evidence in support of this view obtained from healthy
      participants. The results shed light on the representational structure of
      abstract and concrete concepts.

PMID- 19110240
TI  - Feelings of control: contingency determines experience of action.
AB  - The experience of causation is a pervasive product of the human mind. Moreover,
      the experience of causing an event alters subjective time: actions are perceived
      as temporally shifted towards their effects [Haggard, P., Clark, S., & Kalogeras,
      J. (2002). Voluntary action and conscious awareness. Nature Neuroscience, 5(4),
      382-385]. This temporal shift depends partly on advance prediction of the effects
      of action, and partly on inferential "postdictive" explanations of sensory
      effects of action. We investigated whether a single factor of statistical
      contingency could explain both these aspects of causal experience. We studied the
      time at which people perceived a simple manual action to occur, when statistical
      contingency indicated a causal relation between action and effect, and when no
      such relation was indicated. Both predictive and inferential "postdictive" shifts
      in the time of action depended on strong contingency between action and effect.
      The experience of agency involves a process of causal learning based on
      statistical contingency.

PMID- 19110241
TI  - Elucidation of abnormal fertilization by single-cell analysis with fluorescence
      in situ hybridization and polymorphic marker analysis.
AB  - OBJECTIVE: To analyze the genetic composition of oocytes and embryos presenting
      abnormal fertilization. DESIGN: Case report. SETTING: In vitro fertilization unit
      of a university-affiliated hospital. PATIENT(S): A couple with unexplained
      infertility with abnormal fertilizations in nine failed IVF-intracytoplasmic
      sperm injection cycles characterized by the presence of embryos with only one
      pronucleus and nonextrusion of the second polar body. INTERVENTION(S): All first
      polar bodies and blastomeres were analyzed by fluorescence in situ hybridization
      for chromosomes 13, 18, 21, X, and Y. Because some of the one-pronucleus embryos
      were found to be diploid, they were subjected further to single-cell polymerase
      chain reaction analysis with use of a panel of highly polymorphic markers from
      chromosomes 6, 7, 17, 19, X, and Y. MAIN OUTCOME MEASURE(S): Fluorescence in situ
      hybridization analysis of polar bodies and blastomeres and polymorphic marker
      analysis of day 5 embryos. RESULT(S): Fluorescence in situ hybridization analysis
      of the first polar body demonstrated normal segregation of chromosomes in meiosis
      I. Fluorescence in situ hybridization analysis of two aspirated blastomeres
      demonstrated three diploid and two mosaic triploid embryos. Polymorphic marker
      analysis, however, demonstrated that all embryos, including the diploid ones, had
      two sets of maternal alleles. CONCLUSION(S): Single-cell genetic analysis
      routinely used for preimplantation genetic diagnosis may provide insight into the
      genetic composition of oocytes and embryos. These data may be used in cases of
      abnormal fertilization or impaired embryo development for evidence-based
      fertility counseling regarding prognosis and treatment options.

PMID- 19110242
TI  - Successful management of a cervical twin pregnancy: neoadjuvant systemic
      methotrexate and prophylactic high cervical cerclage before curettage.
AB  - OBJECTIVE: To report our experience in managing a case of viable cervical twin
      pregnancy with systemic methotrexate and 2 weeks later with endocervical
      curettage after placing prophylactic high cervical cerclage. DESIGN: Case report.
      SETTING: University medical center. PATIENT(S): A 36-year-old woman, gravida 2,
      para 0, complaining of vaginal bleeding and pelvic pain, in whom cervical twin
      pregnancy was diagnosed at the sixth week of gestation. INTERVENTION(S): Systemic
      methotrexate was given as first-line treatment. Two weeks later because of
      persisting bleeding, endocervical curettage was performed after closing cervical
      arteries and placing but not tightening high cervical cerclage. MAIN OUTCOME
      MEASURE(S): Pregnancy termination, bleeding control, and preservation of
      fertility. RESULT(S): Notwithstanding the ligature of cervical arteries at
      curettage, heavy bleeding occurred, which was controlled rapidly by tightening
      the cerclage. Curettage then was completed successfully. Postoperative period was
      uneventful. Two years later the woman delivered vaginally. CONCLUSION(S): In case
      of cervical twin pregnancy methotrexate pretreatment and prophylactic placement
      of high cervical cerclage, but not ligature of cervical arteries, before
      curettage showed to be effective in terminating pregnancy ensuring effective
      bleeding control and preservation of fertility.

PMID- 19110243
TI  - Boy born after gender preselection following successive gestational androgen
      excess of maternal luteoma and female disorders of sex development.
AB  - OBJECTIVE: To present male gender preselection after successive gestational
      hyperandrogenism and female pseudohermaphroditism by pregnancy luteomas. DESIGN:
      Case report. SETTING: University-based teaching hospital. PATIENT(S): We describe
      herein a gravida who presented two successive 46, XX disorders of sex development
      with apparent female genitalia with an enlarged clitoris due to maternal androgen
      excess from pregnancy luteoma. The maternal hyperandrogenemia returned to a
      normal level and bilateral luteoma regressed spontaneously postpartum. After
      gender preselection by Y-bearing spermatozoa for intrauterine insemination at the
      third gestation, a healthy boy was born in spite of the exaggerated maternal
      androgen production of pregnancy luteoma to avoid 46, XX disorders of sex
      development. INTERVENTION(S): Y-bearing spermatozoa for intrauterine insemination
      as male gender preselection. MAIN OUTCOME MEASURE(S): Boy born after gender
      preselection for intrauterine insemination and cesarean section. RESULT(S):
      Healthy boy born without disorder of sex development after antenatal maternal
      androgen excess of ovarian luteoma. CONCLUSION(S): Successive pregnancy luteomas
      associated with maternal hyperandrogenism may cause female disorders of sex
      development. Male preselection ameliorates the insult of external genitalia
      ambiguity by antenatal androgen excess in this matter of concern.

PMID- 19110244
TI  - Comments on the "Sensor calibration and compensation using artificial neural
      network", by Khan S.A., Shahani D.T., Agarwala A.K.

PMID- 19110245
TI  - Effect of integrated yoga on stress and heart rate variability in pregnant women.
AB  - OBJECTIVE: To study the effect of integrated yoga practice and guided yogic
      relaxation on both perceived stress and measured autonomic response in healthy
      pregnant women. METHOD: The 122 healthy women recruited between the 18th and 20th
      week of pregnancy at prenatal clinics in Bangalore, India, were randomized to
      practicing yoga and deep relaxation or standard prenatal exercises 1-hour daily.
      The results for the 45 participants per group who completed the study were
      evaluated by repeated measures analysis of variance. RESULTS: Perceived stress
      decreased by 31.57% in the yoga group and increased by 6.60% in the control group
      (P=0.001). During a guided relaxation period in the yoga group, compared with
      values obtained before a practice session, the high-frequency band of the heart
      rate variability spectrum (parasympathetic) increased by 64% in the 20th week and
      by 150% in the 36th week, and both the low-frequency band (sympathetic), and the
      low-frequency to high-frequency ratio were concomitantly reduced (P<0.001 between
      the 2 groups). Moreover, the low-frequency band remained decreased after deep
      relaxation in the 36th week in the yoga group. CONCLUSION: Yoga reduces perceived
      stress and improves adaptive autonomic response to stress in healthy pregnant
      women.

PMID- 19110246
TI  - Multiple eccrine hidrocystomas of the vulva.

PMID- 19110247
TI  - A twin study of heritability of plasma lipoprotein-associated phospholipase A2
      (Lp-PLA2) mass and activity.
AB  - OBJECTIVE: We investigated heritability of plasma levels (mass) and activity of
      lipoprotein-associated phospholipase A(2) (Lp-PLA(2)). MATERIALS AND METHODS: In
      54 healthy twins pairs we estimated genetic variance and heritability of Lp
      PLA(2) mass and activity using maximum likelihood and least squares methods. We
      estimated intra-class correlation (ICC) and proportion of additive genetic
      variance from a model comprising additive genetic influence (A), environmental
      effect common to cotwins (C) and individually unique environmental (E) influence
      (ACE) model. RESULTS: Twenty-six twin pairs were monozygotic (MZ) and 28
      dizygotic (DZ). The Lp-PLA(2) mass and activity showed a significant correlation
      (r=0.87, p<0.001) and the mean values were similar in MZ and DZ. ICC estimates of
      heritability for Lp-PLA(2) were 0.27 (mass) and 0.28 (activity); ACE model-based
      estimates of heritability were 0.37 (mass) and 0.54 (activity). Heritability
      estimates were not significant for Lp-PLA(2) mass, but significant for Lp-PLA(2)
      activity. CONCLUSIONS: These results suggest heritability for activity, but not
      for mass, in healthy Caucasians.

PMID- 19110248
TI  - Lipid compounds of the umbilical cord artery and their alterations in
      preeclampsia.
AB  - The lipid composition of arterial walls changes during development, ageing and
      pathological processes. Preeclampsia is the most common pregnancy-associated
      pathological syndrome. It is accompanied by significant remodelling of the
      extracellular matrix, both in the umbilical cord vessels and in the surrounding
      Wharton's jelly. Lipids of the umbilical cord have not been extensively studied.
      Here we evaluate the lipid composition of the umbilical cord artery (UCA) and its
      alteration in preeclampsia. Thin layer chromatography and high-performance liquid
      chromatography were employed for these analyses. It was found that the UCA wall,
      as with most human tissues, contains free fatty acids, mono-, di- and
      triacylglycerols, free cholesterol and its esters. The characteristic feature of
      the UCA wall is the presence of high amounts of long chain polyunsaturated fatty
      acids (PUFA), including eicosapentaenoic acid (C20:5) and docosahexaenoic acid
      (C22:6), which are rather minor lipid components of most human tissues. They
      exist both in a free form and in a form of acylglycerols and cholesterol esters.
      Preeclampsia is associated with a marked decrease in most free fatty acids and
      acylglycerols. The total amount of long chain PUFA: C18:2, C:18:3, C20:4, C20:5
      and C22:6 in these lipid fractions is decreased by half, with a concomitant
      increase in free cholesterol and its esters. We propose that these lower levels
      of PUFA may reduce prostaglandin synthesis in the arterial wall and thereby
      impair blood flow in the foetal vascular system, leading to preeclamptic
      symptoms.

PMID- 19110249
TI  - Anti-atherogenic effects of montelukast associated with reduced MCP-1 expression
      in a rabbit carotid balloon injury model.
AB  - Atherosclerosis is characterized by inflammatory responses of the arterial wall
      to "injury", which is prominently driven by inflammatory mediators. Montelukast,
      a selective CysLT1 receptor antagonist, has potent anti-inflammatory effects in
      diverse animal models. However, the role of montelukast in regulating
      inflammatory progression of atherosclerosis has not been elucidated. Therefore,
      we investigated the effect of montelukast on atherosclerosis compared with that
      of atorvastatin. Twenty-six male New Zealand White rabbits were randomized into
      four groups including a negative control group. The rabbits were fed a normal
      diet or an atherogenic diet for 12 weeks. The rabbits, except the negative
      control group, received right carotid artery balloon-injury 2 weeks after
      initiation of the atherogenic diet. Animals were then treated with montelukast
      (1mg/kg/day), atorvastatin (1.5mg/kg/day) or placebo for 4 weeks, respectively.
      At the end of the treatment, animals were killed and carotids were dislodged and
      detected. The results indicated that the placebo group had significant
      progression of atherosclerosis compared with the negative control group. In
      contrast, montelukast or atorvastatin treated rabbits showed a significant
      reduction of neointima, decreased macrophage content, increased SMC content and
      inhibited expression of MCP-1. Between two drugs, there were no significant
      differences in reducing neointima and decreasing the level of MCP-1. However,
      montelukast had no influence on plasma lipids, while atorvastatin down-regulated
      the levels of TC, TG and LDL. These results suggest that montelukast produces
      anti-atherogenic effects unrelated to plasma lipid modulation but related to MCP
      1 down regulation.

PMID- 19110250
TI  - Circulating oxidized LDL levels, current smoking and obesity in postmenopausal
      women.
AB  - OBJECTIVE: The aim of the present study was to estimate circulating oxidized low
      density lipoprotein (oxLDL) levels in postmenopausal women and evaluate their
      association with obesity and smoking status. DESIGN AND METHODS: The study
      included 135 postmenopausal women aged 52-75 years. Forty of them were overweight
      (BMI 32.4+/-6.4) and non-smokers (Group A), 40 non-overweight (BMI 22.6+/-1.8)
      and smokers (Group B) and 55 non-overweight (BMI 23.5+/-1.4) and non-smokers
      (Group C). oxLDL and antibodies against them (anti-oxLDL) were measured using
      ELISA. Serum total cholesterol, LDL, HDL and triglycerides were measured in an
      automated analyzer. RESULTS: Total cholesterol, LDL, HDL and oxLDL serum levels
      were significantly elevated in Group A as compared to Group B or C, as well as
      oxLDL in Group B in comparison to Group C (p<0.001). Triglycerides and anti-oxLDL
      were increased in Group A in comparison to Group C (p=0.043 and 0.023). Total
      cholesterol, LDL, triglycerides and anti-oxLDL did not differ between Groups B
      and C, while HDL was decreased in Group B as compared to Group C (p<0.001). A
      significant positive correlation was found between oxLDL and LDL in Group A
      (r=0.53, p<0.001) as well as in Group C (r=0.955, p<or=0.001) and a negative one
      between oxLDL and HDL in Group C (r=-0.933, p<0.001). Regression analysis
      revealed that obesity was a stronger predictor of LDL oxidation than smoking.
      CONCLUSIONS: Postmenopausal obesity is involved in the process of LDL oxidation
      and appears to be a stronger predictor of LDL oxidation than smoking. Future
      studies are needed to confirm these associations.

PMID- 19110251
TI  - Analysis of the biodynamic interaction between the fingertip and probe in the
      vibrotactile tests: the influences of the probe/fingertip contact orientation and
      static indentation.
AB  - Vibrotactile thresholds at the fingertips are affected by a number of individual,
      environmental, and testing factors. In the current study, we theoretically
      analyzed the effects of the contact orientation of the probe on the fingertip and
      the static pre-indentation on the dynamic deformation of the soft tissues of the
      fingertip in the vibrotactile tests using a nonlinear finite element model. The
      fingertip considered in the 3D finite element model is the distal phalanx, the
      portion from the distal end to the distal interphalangeal (DIP) joint
      articulation. The fingertip is contacted by the probe at four different contact
      locations, which are regulated by contact angles (15 degrees, 30 degrees, 45
      degrees, and 60 degrees), and three different pre-indentations (0.5, 1.0, and 1.5
      mm). The model predictions indicated that the average spatial summation of the
      vibration displacement (SVD) at the fingertip depends on the static pre
      indentation and the probe/indentor contact orientation; although the resonance
      characteristics of the fingertip are not affected by either the pre-indentation
      or the contact location. The location-dependence of the vibration exposure
      factors at the fingertip was found to increase with increasing static pre
      indentation. At a static indentation of 1.5 mm, the test condition specified in
      the ISO-13091-1 standard, the values of the SVDs determined at different
      probe/fingertip contact orientations differ as much as 125%. Since the dynamic
      displacements of the soft tissues are believed to affect the vibrotactile
      threshold, the current results suggest that the contact orientation of the probe
      on the fingertip should be strictly defined and restricted to obtain reliable
      results in the vibrotactile perception threshold tests.

PMID- 19110252
TI  - Nutrient distribution and metabolism in the intervertebral disc in the unloaded
      state: a parametric study.
AB  - A 2-D finite element model for the intervertebral disc in which quadriphasic
      theory is coupled to the transport of solutes involved in cellular nutrition was
      developed for investigating the main factors contributing to disc degeneration.
      Degeneration is generally considered to result from chronic disc cell nutrition
      insufficiency, which prevents the cells from renewing the extracellular matrix
      and thus leads to the loss of proteoglycans. Hence, the osmotic power of the disc
      is decreased, causing osmomechanical impairments. Cellular metabolism depends
      strongly on the oxygen, lactate and glucose concentrations and on pH in the disc.
      To study the diffusion of these solutes in a mechanically or osmotically loaded
      disc, the osmomechanical and diffusive effects have to be coupled. The
      intervertebral disc is modeled here using a plane strain formulation at the
      equilibrium state under physiological conditions after a long rest period (called
      unloaded state). The correlations between solute distribution and various
      properties of healthy and degenerated discs are investigated. The numerical
      simulation shows that solute distribution in the disc depends very little on the
      elastic modulus or the proteoglycan concentration but greatly on the porosity,
      diffusion coefficient and endplate diffusion area. This coupled model therefore
      opens new perspectives for investigating intervertebral disc degeneration
      mechanisms.

PMID- 19110253
TI  - High-temperature two-dimensional gas chromatography of hydrocarbons up to nC60
      for analysis of vacuum gas oils.
AB  - In a tense energetic context, the characterization of heavy petroleum fractions
      becomes essential. Conventional comprehensive two-dimensional gas chromatography
      (2D-GC or GCxGC) is widely used for middle distillates analysis, but only a few
      applications are devoted to these heavier fractions. In this paper, it is shown
      how the optimization of GCxGC separation allowed the determination of suitable
      high-temperature (HT) conditions, adjusting column properties and operating
      conditions. 2D separations were evaluated using 2D separation criteria and a new
      concept of 2D asymmetry (As(2D)). New HT conditions allowed the extension of
      GCxGC range of applications to heavier hydrocarbons, up to nC(60). A first
      application of high-temperature two-dimensional gas chromatography (HT-2D-GC) to
      a full vacuum gas oil (VGO) feed stock is described. Comparisons with other
      standardized methods illustrate the high potential of HT-2D-GC for heavy
      fractions analysis.

PMID- 19110254
TI  - On-line coupled dynamic sonication-assisted extraction-liquid chromatography for
      the determination of phenolic acids in Lamiaceae herbs.
AB  - A fast and efficient on-line coupled dynamic sonication-assisted extraction
      liquid chromatography (DSAE-LC) method was developed for the determination of
      phenolic acids in basil, oregano, rosemary, sage, spearmint and thyme. The
      extraction and chromatography were coupled via a solid-phase trap filled with
      strong anion exchange material. The relative standard deviations (RSDs) for the
      retention times were less than 0.4% and those for the peak heights less than 3%
      except for gallic acid (RSD 1.2% for the retention times and 11% for the peak
      heights). Limits of detection were below approximately 3ng.

PMID- 19110255
TI  - New 18-l process-scale counter-current chromatography centrifuge.
AB  - A new Dynamic Extractions Maxi-counter-current chromatography (CCC) centrifuge
      with a column volume of 18-l has been installed in the Advanced Bioprocessing
      Centre at Brunel. This instrument has four times the capacity of the 4.6-l Maxi
      CCC centrifuge which has been operating robustly for 3 years. Tests using the
      model sample system benzyl alcohol and p-cresol with a heptane:ethyl
      acetate:methanol:water (HEMWat) phase system (1.4:0.1:0.5:1.0) show that
      resolution is almost double with this new high capacity device. Commissioning
      tests with a mixture of caffeine, K(D)=0.21; ferulic acid, K(D)=0.82;
      umbelliferone, K(D)=1.2 and vanillin, K(D)=1.49 using a HEMWat phase system of
      1:1.5:1:1.5 on the 9-l column show that resolutions equivalent to analytical
      instruments will be possible using the full 18-l capacity. They also show that
      predictable scale-up from simple test tube tests is feasible with knowledge of
      the stationary phase retention for the planned process scale run.

PMID- 19110256
TI  - Synthesis and application of a novel single-isomer mono-6-deoxy-6-(3R,4R
      dihydroxypyrrolidine)-beta-cyclodextrin chloride as a chiral selector in
      capillary electrophoresis.
AB  - A novel positively charged single-isomer of beta-cyclodextrin, mono-6-deoxy-6
      (3R,4R-dihydroxypyrrolidine)-beta-CD chloride (dhypy-CDCl), was synthesized and
      employed as a chiral selector for the first time in capillary electrophoresis
      (CE) for the enantioseparation of anionic and ampholytic acids. The effects of
      the running buffer pH, chiral selector concentration, analyte structure and
      organic modifier on the enantioseparation were studied in detail. The chiral
      selectivity and resolution for most of the studied analytes decreased as the
      buffer pH increased in the range of 6.0-9.0. Increasing selector concentration
      led to decreased effective mobility, increased chiral selectivity and resolution
      for most of the studied analytes. Moreover, the hydroxyl groups located on the
      dihydroxypyrrolidine substituent of the dhypy-CDCl could have influence on the
      chiral separation.

PMID- 19110257
TI  - High-performance liquid chromatographic enantioseparation of 2-aminomono- and
      dihydroxycyclopentanecarboxylic and 2-aminodihydroxycyclohexanecarboxylic acids
      on macrocyclic glycopeptide-based phases.
AB  - The direct separation of the enantiomers of four 2-aminomono- or
      dihydroxycyclopentanecarboxylic acids and four 2
      aminodihydroxycyclohexanecarboxylic acids was performed on chiral stationary
      phases containing macrocyclic glycopeptide antibiotics such as teicoplanin (Astec
      Chirobiotic T and T2), teicoplanin aglycone (Chirobiotic TAG) or ristocetin A
      (Chirobiotic R) as chiral selectors. The effects of the nature of organic
      modifiers, the pH, the mobile phase composition and the structures of the
      analytes on the separation were investigated. Chirobiotic TAG, and in some cases
      Chirobiotic T, proved to be the most useful of these columns. The elution
      sequence was determined in most cases.

PMID- 19110259
TI  - Effect of analyte properties on the kinetic performance of liquid chromatographic
      separations.
AB  - Advances in modern high-performance liquid chromatography (HPLC) have led to
      increased interest in the comparison of the ultimate performance limits of
      methodologies aimed at increasing the resolving power per unit time. Kinetic plot
      based methods have proven invaluable in facilitating such evaluations. However,
      in bridging the gap between fundamental comparisons and the eventual practical
      applicability of kinetic performance data, the effect of analyte properties have
      thus far largely been neglected. Using pharmaceutical compounds as representative
      real-life analytes, it is demonstrated that noteworthy differences in the optimal
      kinetic performance of a chromatographic system are observed compared to data for
      common test compounds. For a given stationary phase particle size, higher optimal
      and maximum plate numbers, corresponding to increased analysis times, are
      measured for pharmaceutical compounds. Moreover, it is found that the optimal
      particle size/maximum pressure combination depends on the analyte under
      investigation, with the beneficial range of efficiencies for small particles
      shifted towards higher plate numbers for drug molecules. It is further
      demonstrated that the pH of the mobile phase plays a crucial role in determining
      the kinetic performance of pharmaceutical compounds. These data clearly indicate
      that data for test compounds do not reflect the performance attainable for
      pharmaceutical compounds and highlights the importance of using real-life samples
      to perform kinetic evaluations.

PMID- 19110258
TI  - Multivariate approach for the enantioselective analysis in micellar
      electrokinetic chromatography-mass spectrometry. I. Simultaneous optimization of
      binaphthyl derivatives in negative ion mode.
AB  - A mixture of two molecular micelles polysodium N-undecenoxy carbonyl-L-leucinate,
      (poly-L-SUCL) and polysodium N-undecanoyl leucylvalinate, (poly-L-SULV) was
      utilized in micellar electrokinetic chromatography-electrospray ionization-mass
      spectrometry (MEKC-ESI-MS) to simultaneously separate and detect enantiomers of
      binaphthyl derivatives. Separation parameters such as background buffer
      composition, voltage, temperature, and nebulizer pressure were optimized using a
      multivariate central composite design (CCD). Baseline enantioseparation for both
      analytes was achieved. The CCD was also used in the optimization of sheath liquid
      and spray chamber parameters to achieve optimum ESI-MS response. The results
      demonstrate that CCD is a powerful tool for the optimization of MEKC-MS
      parameters and the response surface model analysis can provide in-depth
      statistical understandings of the significant factors required to achieve maximum
      enantioresolution and ESI-MS sensitivity.

PMID- 19110260
TI  - Pathological changes in the respiratory tract of goats infected by Pasteurella
      multocida B:2.
AB  - Clinical and pathological changes are described in groups of five goats
      pretreated with dexamethasone and then infected with a large dose of Pasteurella
      multocida B:2 (the cause of haemorrhagic septicaemia) by the intratracheal,
      subcutaneous or intranasal route (groups A, B and C, respectively). In group A,
      two goats died (on day 1 and 4 post-inoculation); in group B three died (days 2,
      5 and 14); and in group C one died (day 20). The infecting organism was recovered
      from the four goats that died within < or =5 days. The major pulmonary lesions
      included acute pneumonia, congestion, oedema and hydrothorax. Subcutaneous oedema
      of the lower jaw and brisket, typically seen in cattle and buffalo, was absent in
      goats.

PMID- 19110261
TI  - Morphological and immunohistochemical studies of spontaneous mammary tumours in
      Siberian hamsters (Phodopus sungorus).
AB  - Mammary tumours from 12 domestic Siberian hamsters (11 females, 1 male) were
      examined. Histopathology revealed three subtypes: simple adenoma, tubulopapillary
      carcinoma, and complex carcinoma. In five cases of malignant mammary tumour,
      focal infiltration into the surrounding fibrous connective tissue was present;
      however, no invasion of either lymphatics or blood vessels was observed. Apocrine
      secretion from neoplastic luminal epithelial cells was prominent in all tumours.
      Expression of oestrogen receptor alpha, progesterone receptor, and androgen
      receptor was evaluated immunohistochemically in neoplastic epithelial cells. Ten
      of the 12 tumours were positive for androgen receptor and all were negative for
      progesterone receptor. Five tumours expressed oestrogen receptor alpha.

PMID- 19110262
TI  - Formulaic quantification of echocardiographic left atrial volume.
AB  - INTRODUCTION: The association between increasing severity in abnormal atrial
      depolarization and left atrial (LA) volume derived by transthoracic
      echocardiogram (TTE) has been described through the following regression formula:
      LA end-systolic volume index (LAVI [milliliter]) = 8.0 + 0.2 (P-wave duration
      [millisecond]) (r = 0.47; P = .0002). However, prospective assessment of this
      formula has not been validated among inpatients outside the institution where it
      was first derived. METHODS: We prospectively obtained 12-lead electrocardiograms
      (ECGs) and TTEs on consecutive inpatients who were scheduled for nonemergent
      echocardiographic assessment. P waves were assessed independently to the nearest
      10 milliseconds for application of the formula with a Bland-Altman plot. P-wave
      durations were obtained specifically from lead II and also from the any lead that
      yielded the widest measurement. RESULTS: After excluding those with poor ECG
      tracing and TTE images, 72 patients were studied. We found a strong formulaic
      correlation with LAVI by TTE when maximal P-wave measurements were obtained from
      any ECG lead (r = 0.67; P < .0001) and more so, when restricted only to lead II
      (r = 0.89; P < .0001). Correlation was strongest when there was no or minimal
      difference between P-wave measurements in lead II and all other leads (r = 0.84;
      P < .0001 for no difference vs r = 0.67; P < .0001 for 60-millisecond
      difference). The Bland-Altman plot showed good agreement of LAVI assessment using
      the formulaic estimation when compared to TTE measurements derived by Simpson's
      rule (coefficient of reproducibility for 2 SD equivalent to 8.8% for lead II and
      11.4% for any lead). CONCLUSION: There is good agreement and correlation between
      formulaic estimation and that of TTE for LAVI among inpatients. Such
      quantification of LA size not only serves as an indirect asset that could perhaps
      supplement TTE measurements in certain circumstances but also can facilitate risk
      stratification of patients.

PMID- 19110263
TI  - Bad cable, good cable.

PMID- 19110264
TI  - Antipsychotic-induced body weight gain: predictors and a systematic
      categorization of the long-term weight course.
AB  - OBJECTIVE: To explore the impact of premorbid and baseline body mass indices
      (BMIs) as well as BMI of patient's parents and associated variables on the
      prediction of antipsychotic-induced body weight gain. METHODS:
      Retrospective/cross-sectional data of 65 patients receiving clozapine, olanzapine
      and/or risperidone were assessed according to a systematic categorization of the
      long-term (7.3+/-9.2 years) weight course and evaluated using descriptive,
      explorative correlation and regression analyses. RESULTS: Increased values of
      parents' BMI (p=0.041) and patients' BMI at premorbid stage (p=0.039) and prior
      to first antipsychotic treatment (p=0.032) as well as female gender (p=0.012),
      younger age (p=0.005) and non-smoking (p=0.047) have the most predictive value on
      body weight gain under antipsychotic treatment including pre-treatment with
      typical antipsychotics. Weight gain under atypical antipsychotics (pre-treatment
      excluded) is predicted by an increased premorbid BMI (p=0.019). Conversely, a low
      BMI prior to first antipsychotic treatment predicts a higher acceleration of BMI
      change (p=0.008) in vulnerable individuals, but not total BMI change itself.
      Furthermore, a diagnosis of a schizophrenia spectrum disorder showed a trend
      towards the prediction of an increased atypical DeltaBMI (p=0.067), possibly due
      to a longer treatment duration with atypical antipsychotics (p<0.001).
      DISCUSSION: The study indicates increased parents' BMI and patients' premorbid
      BMI, female gender, younger age and - as a trend - the diagnosis of a
      schizophrenia spectrum disorder to be predictors for antipsychotic-induced body
      weight gain involving atypical antipsychotics. Data contribute to the assumption
      of a strong impact of predispositional factors on weight gain, besides treatment
      related factors.

PMID- 19110265
TI  - Proteomic analysis of dorsolateral prefrontal cortex indicates the involvement of
      cytoskeleton, oligodendrocyte, energy metabolism and new potential markers in
      schizophrenia.
AB  - Schizophrenia is likely to be a consequence of serial alterations in a number of
      genes that, together with environmental factors, will lead to the establishment
      of the illness. The dorsolateral prefrontal cortex (Brodmann's Area 46) is
      implicated in schizophrenia and executes high functions such as working memory,
      differentiation of conflicting thoughts, determination of right and wrong
      concepts, correct social behavior and personality expression. We performed a
      comparative proteome analysis using two-dimensional gel electrophoresis of pools
      from 9 schizophrenia and 7 healthy control patients' dorsolateral prefrontal
      cortex aiming to identify, by mass spectrometry, alterations in protein
      expression that could be related to the disease. In schizophrenia-derived
      samples, our analysis revealed 10 downregulated and 14 upregulated proteins.
      These included alterations previously implicated in schizophrenia, such as
      oligodendrocyte-related proteins (myelin basic protein and transferrin), as well
      as malate dehydrogenase, aconitase, ATP synthase subunits and cytoskeleton
      related proteins. Also, six new putative disease markers were identified,
      including energy metabolism, cytoskeleton and cell signaling proteins. Our data
      not only reinforces the involvement of proteins previously implicated in
      schizophrenia, but also suggests new markers, providing further information to
      foster the comprehension of this important disease.

PMID- 19110267
TI  - Effect of tamsulosin on systemic blood pressure and nonneurogenic dysfunctional
      voiding in children.
AB  - PURPOSE: A number of therapies for dysfunctional voiding in children have been
      proposed after conservative measures have failed. Prior studies have shown
      significant improvement in lower urinary tract symptoms with alpha1-adrenergic
      antagonists. Nonselective alpha1-adrenergic antagonists can result in systemic
      vasodilatation and hypotension. We examined the effects of tamsulosin, a
      uroselective alpha1A-adrenergic antagonist, on blood pressure, as well as its
      safety and efficacy in the treatment of dysfunctional voiding in a pediatric
      population. MATERIALS AND METHODS: A total of 23 children without anatomical or
      neurogenic abnormalities presented with lower urinary tract symptoms refractory
      to conservative measures. All children had increased post-void residual urine or
      abnormal uroflowmetry in the absence of pelvic floor activity suggestive of
      bladder neck dysfunction. All patients were administered tamsulosin daily.
      Voiding diaries, blood pressure, uroflowmetry studies and patterns along with
      assessment of post-void residual urine were obtained before and after beginning
      tamsulosin in all children. RESULTS: Median duration of tamsulosin therapy was 7
      months, and patient followup was 20 months. The number of voiding and incontinent
      episodes significantly decreased during treatment compared to baseline (p <0.05).
      Mean blood pressures before and during tamsulosin treatment were 98/55 mm Hg and
      110/61 mm Hg, respectively. Significant increases in average and maximum urinary
      flow rates along with reduction in post-void residual urine were observed during
      tamsulosin therapy compared to baseline values (p <0.01). A 50% reduction in the
      number of abnormal uroflow patterns was observed with tamsulosin therapy.
      CONCLUSIONS: Tamsulosin demonstrated no clinically significant effect on blood
      pressure, while proving to be a safe and effective treatment option for lower
      urinary tract symptoms in a select pediatric population.

PMID- 19110268
TI  - A population based study of 2,856 school-age children with urinary incontinence.
AB  - PURPOSE: We estimated the spectrum and risk factors for daytime urinary
      incontinence in school-age children. MATERIALS AND METHODS: A validated,
      reproducible, parent administered daytime incontinence questionnaire was
      distributed to randomly selected school children. The questionnaire elicited
      information on demographic factors, prenatal and developmental factors, and bowel
      and urinary history. The spectrum of daytime urinary incontinence was measured by
      recording the frequency and amount of incontinence. RESULTS: Parents of 2,856
      children (mean age 7.3 years) completed the questionnaire. Overall 16.9% reported
      any daytime urinary incontinence in the previous 6 months, with 64% of cases
      being very mild, 14.8% mild, 11.6% moderate and 9.6% severe. There was low
      agreement between frequency and amount of incontinence (weighted kappa 0.03) but
      risk factors were similar. Independent risk factors were nocturnal enuresis (OR
      7.2, 95% CI 3.4 to 15.2), female gender (5.4, 2.6 to 11.1), social concerns (3.4,
      1.4 to 8.3), urinary tract infection (5.6, 2.0 to 15.6) and encopresis (3.3, 1.4
      to 7.7). Expressed as population attributable risk, 36% of moderate to severe
      daytime incontinence can be attributed to encopresis, nocturnal enuresis, social
      concerns, female gender or urinary tract infection. Urinary tract infection was a
      risk factor for boys but not for girls (interaction p <0.01). CONCLUSIONS:
      Daytime urinary incontinence in children is a common but heterogeneous disorder.
      Episodes may be frequent or major or both but appear to share the same causal
      pathway. Given the risk factors identified, interventions should target
      endogenous/physiological and environmental factors.

PMID- 19110271
TI  - Re: Urinary retention and post-void residual urine in men: separating truth from
      tradition: S. A. Kaplan, A. J. Wein, D. R. Staskin, C. G. Roehrborn and W. D.
      Steers, J Urol 2008; 180: 47-54.

PMID- 19110272
TI  - Re: The true incidence of cryptorchidism in Denmark: D. Cortes, E. M. Kjellberg,
      M. Breddam and J. Thorup, J Urol 2008; 179: 314-318.

PMID- 19110274
TI  - Re: Predictive factors for contralateral reflux in patients with conservatively
      treated unilateral vesicoureteral reflux: U. Barroso, Jr., V. A. Barroso,J. De
      Bessa, Jr., A. A. Calado and M. Zerati: Filho, J Urol 2008; 180: 297-299.

PMID- 19110275
TI  - Against: No surgery for stuttering priapism.

PMID- 19110277
TI  - Robot assisted laparoscopic partial nephrectomy: a viable and safe option in
      children.
AB  - PURPOSE: The safety, benefits and usefulness of laparoscopic partial nephrectomy
      have been demonstrated in the pediatric population. We describe our technique,
      and determine the safety and feasibility of robot assisted laparoscopic partial
      nephrectomy based on our initial experience. MATERIALS AND METHODS: We
      retrospectively reviewed robot assisted laparoscopic partial nephrectomy
      performed at our institution between 2002 and 2005. The technique was conducted
      via a transperitoneal approach with the da Vinci Surgical System using standard
      laparoscopic procedural steps. Clinical indicators of outcomes included estimated
      blood loss, complications, in hospital narcotic use and length of stay. RESULTS:
      Robot assisted laparoscopic partial nephrectomy was completed successfully in 9
      cases. Mean patient age was 7.2 years and mean followup was 6 months. Mean
      operative time was 275 minutes and mean estimated blood loss was 49 ml. Operative
      times improved significantly with experience. Overall patients had a mean
      hospitalization of 2.9 days and required 1.3 mg morphine per kg. All patients had
      a normal remaining renal moiety confirmed on Doppler ultrasound. The only
      complication was an asymptomatic urinoma discovered on ultrasound, which was
      treated with percutaneous drainage and ultimately resolved. CONCLUSIONS: Our
      initial experience shows the safety and feasibility of robot assisted
      laparoscopic partial nephrectomy in children. Operative time decreases with
      experience. The enhanced visualization and dexterity of a robotic system
      potentially offer improved efficiency and safety over standard laparoscopy. Robot
      assisted laparoscopy is an option for partial nephrectomy and may become the
      minimally invasive treatment of choice.

PMID- 19110278
TI  - Re: Residual urinary volume and urinary tract infection--when are they linked?:
      J. C. Truzzi, F. M. Almeida, E. C. Nunes and M. V. Sadi, J Urol 2008; 180: 182
      185.

PMID- 19110280
TI  - Intraoperative thrombus embolization during nephrectomy and tumor thrombectomy:
      critical analysis of the University of California-Los Angeles experience.
AB  - PURPOSE: Vascular invasion commonly occurs in renal cell carcinoma and
      intraoperative thrombus embolization is a known complication of tumor
      thrombectomy. We reviewed our experience with this complication to determine
      frequency, mortality, common factors and management strategies. MATERIALS AND
      METHODS: We retrospectively reviewed a prospective database of cases of open
      nephrectomy/tumor thrombectomy performed from 1989 to 2008. All cases were
      reviewed to identify clinicopathological variables, the thrombus extent and
      intraoperative complications. All cases with events were reviewed to identify
      preoperative pulmonary embolism, preoperative imaging, thrombus extent,
      presentation, management and outcome. RESULTS: A total of 282 cases of venous
      tumor thrombus were identified. Tumor thrombus level was 0 in 133 cases (47.2%),
      I to II in 85 (30.1%), III in 27 (9.6%) and IV in 29 (10.3%). Thrombus
      embolization was identified in 5 patients (1.8%). The incidence in level 0 vs I
      to IV was 0 of 133 cases (0%) vs 5 of 149 (3.4%), which was statistically
      significant (p = 0.04). Three patients (60%) died of the event. A review of
      recent series demonstrated a 1.49% incidence with 75% mortality. CONCLUSIONS:
      Intraoperative thrombus embolization is rare but when it occurs, mortality is
      extremely high. Strict attention to surgical principles is necessary to decrease
      risk. Extension into the vena cava, preoperative pulmonary embolism and a bland
      thrombus component may indicate increased risk. Adjunct procedures, such as
      preoperative filters and endoluminal occlusive balloons, may be justified in
      patients at high risk. Even with prompt recognition and embolectomy survival is
      rare.

PMID- 19110283
TI  - Re: Laparoscopic ureteroneocystostomy and psoas hitch for post-hysterectomy
      ureterovaginal fistula: P. Modi, R. Gupta and S. J. Rizvi, J Urol 2008; 180: 615
      617.

PMID- 19110286
TI  - A process for comparing and interpreting differences in two benthic indices in
      New York Harbor.
AB  - Often when various estuarine benthic indices disagree in their assessments of
      benthic condition, they are reflecting different aspects of benthic condition. We
      describe a process to screen indices for associations and, after identifying
      candidate metrics, evaluate metrics individually against the indices. We utilize
      radar plots as a multi-metric visualization tool, and conditional probability
      plots and receiver operating characteristic curves to evaluate associations seen
      in the plots. We investigated differences in two indices, the US EPA
      Environmental Monitoring and Assessment Program's benthic index for the Virginian
      Province and the New York Harbor benthic index of biotic integrity using data
      collected in New York Harbor and evaluated overall agreement of the indices and
      associations between each index and measures of habitat and sediment
      contamination. The indices agreed in approximately 78% of the cases. The New York
      Harbor benthic index of biotic integrity showed stronger associations with
      sediment metal contamination and grain size.

PMID- 19110287
TI  - Interaction between attaching-effacing Escherichia coli O26:K60 and O157:H7 in
      young lambs.
AB  - Recent surveys have shown that Escherichia coli O26 is prevalent in ruminants
      compared with E. coli O157. These serogroups share common colonisation factors
      and we hypothesised that prior colonisation by E. coli O26 may show reduced
      colonisation by E. coli O157. To test this hypothesis, strains of E. coli O26:K60
      and O157:H7 were tested in competitive in vitro and in vivo studies. Using an
      established 6-week-old lamb model, an experimental group of lambs was dosed
      orally with E. coli O26:K60 and then E. coli O157:H7 four days later. The faecal
      shedding of O26:K60 and O157:H7 organisms from this experimental group was
      compared with that from animals dosed with either O26:K60 alone or O157:H7 alone.
      Shedding data indicated that counts for O157:H7 were unaffected by the
      competition from O26:K60, whereas the O26:K60 counts were lower when competing
      with O157:H7.

PMID- 19110288
TI  - HIV-1 viral load monitoring: an opportunity to reinforce treatment adherence in a
      resource-limited setting in Thailand.
AB  - This paper describes a program to increase patients' treatment literacy regarding
      viral load (VL) monitoring through patient education materials and a counseling
      protocol, implemented by peer counselors, in order to reinforce adherence to
      first-line treatment. VL monitoring and second-line antiretroviral treatment were
      introduced into an established first-line treatment program in a rural district
      hospital in Thailand. All patients (171 adults and 14 children) taking
      antiretroviral treatment for more than 6 months participated and those with
      detectable VL were targeted for additional adherence support. The main outcome
      measure recorded was the number of detectable results becoming undetectable after
      counseling. Four adults and one child had a persistently high VL and switched to
      second-line treatment. Of 51 adults (30%) with an initial low detectable VL,
      47/51 identified likely explanations, usually linked with poor adherence.
      Following counseling, VL became undetectable in 45/51 cases and some patients
      could resolve long-standing psychosocial problems. We conclude that HIV-1 VL
      monitoring together with targeted counseling for patients with detectable VL can
      promote adherence to treatment, providing an opportunity to delay onset of HIV-1
      resistance. When implemented with a patient-centered approach, it can be a very
      useful tool for psychosocial support.

PMID- 19110289
TI  - Development of calibration techniques for ultrasonic hydrophone probes in the
      frequency range from 1 to 100 MHz.
AB  - The primary objective of this work was to develop and optimize the calibration
      techniques for ultrasonic hydrophone probes used in acoustic field measurements
      up to 100 MHz. A dependable, 100 MHz calibration method was necessary to examine
      the behavior of a sub-millimeter spatial resolution fiber optic (FO) sensor and
      assess the need for such a sensor as an alternative tool for high frequency
      characterization of ultrasound fields. Also, it was of interest to investigate
      the feasibility of using FO probes in high intensity fields such as those
      employed in HIFU (high intensity focused ultrasound) applications. In addition to
      the development and validation of a novel, 100 MHz calibration technique the
      innovative elements of this research include implementation and testing of a
      prototype FO sensor with an active diameter of about 10 microm that exhibits
      uniform sensitivity over the considered frequency range and does not require any
      spatial averaging corrections up to about 75 MHz. The results of the calibration
      measurements are presented and it is shown that the optimized calibration
      technique allows the sensitivity of the hydrophone probes to be determined as a
      virtually continuous function of frequency and is also well suited to verify the
      uniformity of the FO sensor frequency response. As anticipated, the overall
      uncertainty of the calibration was dependent on frequency and determined to be
      about +/-12% (+/-1 dB) up to 40 MHz, +/-20% (+/-1.5 dB) from 40 to 60 MHz and +/
      25% (+/-2dB) from 60 to 100 MHz. The outcome of this research indicates that once
      fully developed and calibrated, the combined acousto-optic system will constitute
      a universal reference tool in the wide, 100 MHz bandwidth.

PMID- 19110290
TI  - Global sensitivity analysis for model-based prediction of oxidative
      micropollutant transformation during drinking water treatment.
AB  - This study quantifies the uncertainty involved in predicting micropollutant
      oxidation during drinking water ozonation in a pilot plant reactor. The analysis
      is conducted for geosmin, methyl tert-butyl ether (MTBE),
      isopropylmethoxypyrazine (IPMP), bezafibrate, beta-cyclocitral and ciprofloxazin.
      These compounds are representative for a wide range of substances with second
      order rate constants between 0.1 and 1.9x10(4)M(-1)s(-1) for the reaction with
      ozone and between 2x10(9) and 8x10(9)M(-1)s(-1) for the reaction with OH
      radicals. Uncertainty ranges are derived for second order rate constants,
      hydraulic parameters, flow- and ozone concentration data, and water
      characteristic parameters. The uncertain model factors are propagated via Monte
      Carlo simulation and the resulting probability distributions of the relative
      residual micropollutant concentrations are assessed. The importance of factors in
      determining model output variance is quantified using Extended Fourier Amplitude
      Sensitivity Testing (Extended-FAST). For substances that react slowly with ozone
      (MTBE, IPMP, geosmin) the water characteristic R(ct)-value (ratio of ozone- to OH
      radical concentration) is the most influential factor explaining 80% of the
      output variance. In the case of bezafibrate the R(ct)-value and the second order
      rate constant for the reaction with ozone each contribute about 30% to the output
      variance. For beta-cyclocitral and ciprofloxazin (fast reacting with ozone) the
      second order rate constant for the reaction with ozone and the hydraulic model
      structure become the dominating sources of uncertainty.

PMID- 19110291
TI  - Effect of pH, ionic strength, dissolved organic carbon, time, and particle size
      on metals release from mine drainage impacted streambed sediments.
AB  - Acid-mine drainage (AMD) input to a stream typically results in the stream having
      a reduced pH, increased concentrations of metals and salts, and decreased
      biological productivity. Removal and/or treatment of these AMD sources is desired
      to return the impacted stream(s) to initial conditions, or at least to conditions
      suitable for restoration of the aquatic ecosystem. Some expected changes in the
      water chemistry of the stream following removal of AMD input include an increase
      in pH, a decrease in ionic strength, and an increase in dissolved organic carbon
      (DOC) concentrations from increased biological activity in the absence of toxic
      metals concentrations. These changes in water chemistry may cause the existing
      contaminated bed sediments to become a source of metals to the stream water.
      Streambed sediments, collected from North Fork Clear Creek (NFCC), Colorado,
      currently impacted by AMD, were assessed for the effects of pH, ionic strength,
      DOC concentration, time, and particle size on metals release using a factorial
      design. The design included two levels for each chemical parameter (ionic
      strength = 40 and 80% lower than ambient; pH = 6 and 8; and DOC = 1 and 3 mg/l
      higher than ambient), ten sampling times (from zero to 48 h), and two size
      fractions of sediments (63 microm < or = x < 2 mm and < 63 microm). Greater
      concentrations of metals were released from the smaller sized sediments compared
      with the larger, with the exception of Cu. A mild acid digestion (0.6M HCl)
      evaluated the amount of each metal that could be removed easily from each of the
      sediment size fractions. Release of all metals over all time points, treatments,
      and from both sediment sizes was less than 1% of the extractable concentrations,
      with the exception of Mn, which ranged from 4 to 7% from the smaller sized
      sediment. Greater percentages of the 0.6M HCl-extractable concentrations of Cu,
      Fe, and Zn were released from the larger sized sediment, while this was true for
      release of Cd and Mn from the smaller sized sediment. Thus, at least for Cd and
      Mn, the observed higher concentrations released from the smaller sized sediment
      with each treatment solution is not simply a function of these particles having
      higher concentrations available for release, but that these metals also are more
      readily released from the smaller sediment particles versus the larger. DOC
      concentration strongly influenced the release of Cu; ionic strength strongly
      influenced the release of Cd, Mn, and Zn; and interaction effects were observed
      with the release of Cu, Mn, and Zn from the larger size fraction and with the
      release of Zn from the smaller size fraction. Overall, results suggest that the
      expected changes in water chemistry following removal/treatment of the AMD
      sources would result in a release of metals from the existing sediments, with a
      greater effect on the release of Cu and Fe, than on the release of Cd, Mn, and
      Zn.

PMID- 19110292
TI  - Occurrence and role of algae and fungi in acid mine drainage environment with
      special reference to metals and sulfate immobilization.
AB  - Passive remediation of Acid Mine Drainage (AMD) is a popular technology under
      development in current research. Roles of algae and fungi, the natural residents
      of AMD and its attenuator are not emphasized adequately in the mine water
      research. Living symbiotically various species of algae and fungi effectively
      enrich the carbon sources that help to maintain the sulfate reducing bacterial
      (SRB) population in predominantly anaerobic environment. Algae produce anoxic
      zone for SRB action and help in biogenic alkalinity generation. While studies on
      algal population and actions are relatively available those on fungal population
      are limited. Fungi show capacity to absorb significant amount of metals in their
      cell wall, or by extracellular polysaccharide slime. This review tries to throw
      light on the roles of these two types of microorganisms and to document their
      activities in holistic form in the mine water environment. This work, inter alia,
      points out the potential and gap areas of likely future research before potential
      applications based on fungi and algae initiated AMD remediation can be made on
      sound understanding.

PMID- 19110293
TI  - Degradation of reactive dyes in wastewater from the textile industry by ozone:
      analysis of the products by accurate masses.
AB  - The present work describes the use of ozone to degrade selected reactive dyes
      from the textile industry and the analysis of the resulting complex mixture by
      liquid chromatography/mass spectrometry (LC-MS). To allow certain identification
      of the substances detected in the wastewater, the original dyes were also
      investigated either separately or in a synthetic mixture of three dyes
      (trichromie). Since the reactive dyes are hydrolyzed during the dyeing process,
      procedures for the hydrolysis were worked out first for the individual dyes. The
      ozonated solutions were concentrated by solid-phase extraction, which separated
      very polar or ionic substances from moderately polar degradation products. The
      latter, which are the primary degradation products, were investigated by liquid
      chromatography/mass spectrometry with a tandem quadrupole time-of-flight mass
      analyzer. Accurate masses, which in most cases could be determined with a
      deviation of <or=5 ppm from the exact value, were also measured. In addition, a
      diode-array detector was placed before the mass analyzer to provide UV-vis
      spectra of the products in the same run. With retention times, mass spectra,
      accurate masses, UV-vis spectra and, of course, knowledge of the structures of
      the original dyes, plausible structures could be proposed for most of the
      components of the moderately polar fraction. These structures were confirmed by
      1H NMR in cases where it was practical to isolate the degradation products by
      preparative HPLC.

PMID- 19110294
TI  - Pb, Zn and Cd mobility, availability and fractionation in aged soil remediated by
      EDTA leaching.
AB  - Soil washing remediation techniques usually remove only the labile heavy metal
      (HM) species from the soil, leaving the residual ones in less available/mobile
      forms, thus disturbing the chemical equilibrium among different species of HM in
      the soil. Re-establishing such equilibrium and shifting HM back to more
      available/mobile chemical forms could occur after exposing the remediated soil to
      environmental abiotic (ageing) factors. Contaminated soil from a smelter site (Pb
      4600 mg kg(-1), Zn 1800 mg kg(-1), Cd 30 mg kg(-1)) was leached with increasing
      EDTA concentrations (2.5, 5.0, 10.0, 20.0, 40.0 and 4-consecutive steps of 40.0
      mmol EDTA kg(-1) of soil). A gradient of removed HM was reached: from 6% to 73%
      of initial Pb, from 3% to 23% of initial Zn and from 17% to 74% of initial Cd
      were removed. Repetitive temperature changes (105 degrees C and -20 degrees C)
      were used to mimic abiotic factors acting on residual HM after EDTA soil leaching
      in saturated soil at 10% and 90% of soil water holding capacity. Fractionation
      using sequential extractions, mobility, and phytoavailability of Pb, Zn and Cd
      and Pb oral bioavailability were determined for aged and non-aged soil. The
      ageing treatment consistently lowered HM phytoavailability in the original (non
      leached) and all treated (chelant-leached) soils. However, Pb, Zn and Cd behaved
      differently from each other; Pb mobility increased, Cd mobility decreased, while
      Zn mobility did not change. The results indicate that abiotic (ageing) processes
      change the availability/mobility of residual HM in all leaching treatments and
      should thus be considered in final remediation effectivity evaluation.

PMID- 19110295
TI  - Competition between selenium (IV) and silicic acid on the hematite surface.
AB  - Competition between selenium (IV) and silicic acid for the hematite (alpha
      Fe(2)O(3)) surface has been studied during this work. Single batch experiments
      have been performed to study separately the sorption of selenium (IV) and silicic
      acid as a function of the pH. With the help of the 2-pK surface complexation
      model, experimental data have been fitted using the FITEQL 4.0 program. Two
      monodentate inner-sphere surface complexes have been used to fit selenite ions
      retention, triple bond FeSeO(3)(-) and triple bond FeHSeO(3). In order to fit
      sorption of silicic acid, the two following surface complexes, namely triple bond
      FeH(3)SiO(4), and triple bond FeH(2)SiO(4)(-), have been used. Using the surface
      complexation constants coming from these two binary systems, prediction curves of
      the effect of silicic acid on the retention of selenium (IV) onto hematite have
      been obtained. Finally, performed experiments showed a competition between
      selenium (IV) and silicic acid for the surface sites of hematite. Experimental
      data matched DDLM predictions, confirming the ability of the surface complexation
      model to predict quantitatively and qualitatively the ternary system selenium
      (IV)/H(4)SiO(4)/hematite.

PMID- 19110296
TI  - Assessment of Donana National Park contamination in Procambarus clarkii:
      integration of conventional biomarkers and proteomic approaches.
AB  - Aquatic ecosystems of Donana National Park (DNP) were monitored using Procambarus
      clarkii as bioindicator in four campaigns carried out between 2003 and 2004 to
      assess environmental quality possibly threatened by agrochemicals used in nearby
      areas. An integrated approach was carried out, by combining the responses of well
      established biomarkers and the massive analysis of biological effects at the
      proteomic level. In sites potentially polluted, lower catalase, glucose-6-P
      dehydrogenase, and esterase activities, and higher malondialdehyde,
      metallothionein and glutathione levels were found. Two-dimensional gel
      electrophoresis resolved >2500 gill spots, and image analysis detected that 35
      showed significant intensity differences between the reference site and the other
      seven sites studied. The superiority of proteomic approaches was clearly
      recognized in our study since four different protein expression patterns were
      established based in the fold-number of up-/down-regulation of the 35
      differentially expressed proteins. Sites located within Donana Biological Reserve
      were essentially free of contaminants and those near the DNP limits were only
      slightly polluted. The higher proteomic responses found at the upper "Rocina" and
      "Partido" courses indicate that non-persistent agrochemicals are mainly used in
      Donana surroundings. The highest responses corresponded to rice growing areas
      placed between the Guadiamar stream and the Guadalquivir River, according to the
      extended and intensive use of agrochemicals in such areas.

PMID- 19110297
TI  - Pre-treatment and bioconversion of wastewater sludge to value-added products-
      fate of endocrine disrupting compounds.
AB  - Development of processes for the production of value added products (VAPs), such
      as biopesticides, microbial inoculants or industrial enzymes through
      biotransformation of raw or pre-treated wastewater sludge (WWS) has undergone a
      substantial progress over the last decade. WWS based VAPs are low cost biological
      alternatives that can compete with chemicals or other cost intensive biological
      products in the current markets. However, when WWS is used as a raw material for
      VAPs production, questions still remains on the persistence of organic pollutants
      within the biotransformed WWS, especially, endocrine disrupting compounds (EDCs)
      and the production of their toxic intermediates. WWS pre-treatment prior to
      biotransformation as well as the microbial strains used for biotransformation can
      possibly remove these organic pollutants. The literature findings concerning the
      impact of WWS pre-treatment and value added products on EDCs removal are reviewed
      in this paper. The microbial potential to degrade or detoxify EDCs and toxic
      intermediates concomitant with value-addition is also discussed. The concept of
      obtaining EDCs free-WWS based VAPs and simultaneously achieving the objective of
      pollution control is presented.

PMID- 19110298
TI  - Systemic immune presentations of Coxiella burnetii infection (Q Fever).
AB  - OBJECTIVES: Q fever is a worldwide zoonosis caused by Coxiella burnetii. Its
      presentation can be atypical, delaying and complicating the diagnosis. We report
      7 cases of Q fever mimicking vasculitis, systemic inflammatory disease, or auto
      immune disorder. METHODS: Seven cases of Q fever diagnosed between 1995 and 2007
      in Nantes University Hospital (France) are described. They occurred in a
      nonendemic region and were selected on the basis of initial clinical presentation
      suggesting systemic immune disease. C. burnetii was detected using indirect
      immunofluorescence serology. RESULTS: Q fever was acute in 4 of the 7 patients
      and chronic in 3. None had endocarditis. The initial presentations suggested
      Crohn's disease, Goodpasture's syndrome, polymyalgia rheumatica, adult-onset
      Still's disease, polyarteritis nodosa, giant-cell arteritis, and essential type
      II cryoglobulinemia. Two patients had antiphospholipid antibodies, 1 had
      transient IgG kappa monoclonal gammopathy, and 1 had polyclonal T CD8+ large
      granular lymphocyte expansion. CONCLUSION: Clinicians must be aware of the
      potential diagnosis of Q fever, and C. burnetii serology is a helpful diagnostic
      tool in the investigation of fever of unknown origin with atypical systemic
      symptoms suggesting vasculitis or inflammatory disease.

PMID- 19110299
TI  - Maternal mixed connective tissue disease and offspring with chondrodysplasia
      punctata.
AB  - OBJECTIVES: To describe the case of a mother with mixed connective tissue disease
      (MCTD) whose male and female offspring from 2 successive pregnancies had
      chondrodysplasia punctata (CDP) in the absence of identifiable biochemical or
      genetic abnormalities or teratogen exposure. METHODS: Description of a male and
      female offspring from a mother with MCTD harboring high-titer anti
      ribonucleoprotein (RNP) antibodies. Maternal autoantibody assays were performed
      employing quantitative multiplex suspension arrays and flow cytometry, and
      autoantibody titer and pattern were determined by indirect immunofluorescence.
      Assays of phytanic acid, plasmalogen, and very long-chain fatty acids were
      performed employing commercially available reagents. Chromosomal analysis was
      performed on both offspring employing standard cytogenetic analysis. Review of
      the relevant literature was performed (PubMed search 1966 through July 2008).
      RESULTS: Two children with CDP born to a mother with MCTD who harbored anti-RNP
      autoantibodies at high titer are described. Genetic and chromosomal studies and
      biochemical analysis of peroxisome function and very long-chain fatty acids
      excluded known biochemical or genetic defects or mutations as the cause of CDP in
      these children. Furthermore, detailed review of the clinical history failed to
      disclose any evidence of maternal teratogen exposure during the 2 pregnancies.
      CONCLUSIONS: Maternal MCTD is the most likely explanation for the occurrence of
      CDP in the 2 children reported here. Review of previously published cases of CDP
      associated with autoimmune disease suggests that placental crossing of maternal
      autoantibodies during pregnancy specifically affecting the normal development of
      fetal growth plates is responsible for CDP in the offspring in these cases.

PMID- 19110300
TI  - Blood group AB and factor V Leiden as risk factors for pre-eclampsia: a
      population-based nested case-control study.
AB  - INTRODUCTION: Pre-eclampsia is an important cause of maternal morbidity and
      mortality. Its etiology is still unknown. Clinical symptoms correlate with
      activation of coagulation and inherited thrombophilia has been associated with
      pre-eclampsia. ABO blood group has been associated with thrombotic disorders and
      pre-eclampsia. We assessed ABO blood group, seven thrombophilia associated
      polymorphisms, and anti-beta2-glycoprotein I antibodies as risk factors for pre
      eclampsia. MATERIALS AND METHODS: We performed a population-based nested case
      control study of 100,000 consecutive pregnancies in Finland. Cases and controls
      were identified by combining national registers and medical records were
      reviewed. We studied 248 cases fulfilling strict criteria for pre-eclampsia and
      679 controls. Severe pre-eclampsia, early pre-eclampsia, and pre-eclampsia with
      intra-uterine growth restriction (IUGR) were analyzed separately. RESULTS: Blood
      group AB increased the risk for pre-eclampsia as a whole (OR 2.1, 95% CI 1.3
      3.5), and in the three subgroups (OR 2.3, 3.8, 3.4; 95% CI 1.3-3.9, 2.0-7.1, 1.6
      7.1). FV Leiden increased the risk as a whole (OR 1.7, 95% CI 0.8-3.9), and in
      the three subgroups, although not statistically significantly. Anti-beta2
      glycoprotein I antibodies were not associated with pre-eclampsia. High body mass
      index, diabetes, first pregnancy, and twin pregnancy increased the risk from 1.5
      fold to 8.2-fold. CONCLUSIONS: Our results confirm and extend the prior
      observation of blood group AB being a risk factor for pre-eclampsia. ABO blood
      group is known from all pregnant women. The value of blood group as risk factor
      for pre-eclampsia should be further assessed in prospective studies. In this
      study, FV Leiden was not statistically significant risk factor.

PMID- 19110301
TI  - Efficacy over time of LHRH analogs in the treatment of PCa--a prospective
      analysis using serum testosterone to determine dosing intervals.
AB  - OBJECTIVES: To examine the duration of serum testosterone and prostate-specific
      antigen suppression after each dose of a 4-month depot leuprolide acetate for 18
      months and to assess the potential for using serum testosterone as a guide for
      redosing the luteinizing hormone-releasing hormone analogs instead of using fixed
      dosing intervals. Luteinizing hormone-releasing hormone analogs are well
      established for the treatment of prostate cancer (PCa). However, many open
      questions remain regarding the optimal dosing. METHODS: Thirteen patients with
      PCa were enrolled in a longitudinal study. Serum testosterone levels were
      obtained at baseline and then monthly beginning 4 months after the first
      injection and every 2 months after the subsequent injections, for a total of 18
      months. The median number of days from injection to the first serum testosterone
      level > or = 50 ng/dL was estimated using the Kaplan-Meier product-limit method.
      RESULTS: The median duration of effect was 159, 189, and 163 days for the first,
      second, and third treatment cycle, respectively. The prostate-specific antigen
      values from entry to completion decreased in all subjects. The total number of
      injections was reduced in all but one subject who completed the 18-month trial.
      One patient developed hormone-refractory PCa. CONCLUSIONS: Serum testosterone
      measurement might be a useful method for redosing luteinizing hormone-releasing
      hormone analogs. Using testosterone levels to determine the time of reinjection
      has a significant economic impact. Monitoring serum testosterone not only helps
      to identify patients who fail to achieve testosterone suppression but also
      provides close monitoring for the potential development of hormone-refractory
      PCa.

PMID- 19110302
TI  - Small cell neuroendocrine carcinoma of the cervix: Analysis of outcome,
      recurrence pattern and the impact of platinum-based combination chemotherapy.
AB  - OBJECTIVES: To analyze progression-free (PFS) and overall survival (OS) in
      patients with small cell neuroendocrine carcinoma of the cervix (SCNEC), and to
      determine whether platinum-based combination chemotherapy is beneficial for this
      population. METHODS: We performed a retrospective analysis of all patients with
      SCNEC who were treated at our institution between 1/1990 and 2/2007. Patients
      were excluded if pathologic diagnosis was not confirmed at our institution.
      Standard statistical methods were utilized. RESULTS: Seventeen patients met
      inclusion criteria. The estimated 3-year PFS and OS rates for the entire group
      were 22% and 30%, respectively. Median time to progression was 9.1 months. Extent
      of disease was the only significant prognostic factor. Median OS for patients
      with early stage disease (IA1-IB2) was 31.2 months and 6.4 months for patients
      with advanced stage disease (IIB-IV, P=0.034). In the early-stage disease group,
      the 3-year distant recurrence-free survival rate was 83% for patients who
      received chemotherapy and 0% for patients who did not receive chemotherapy as
      part of their initial treatment (P=0.025). The estimated 3-year OS rate was 83%
      for patients who received and 20% for patients who did not receive chemotherapy
      as part of their initial treatment (P=0.36). CONCLUSION: Given the rarity of
      SCNEC this retrospective analysis is limited by a small number of patients.
      However, the natural history of this rare disease is akin to small cell lung
      cancer and the prognosis is poor due to the tumor's propensity for distant
      spread. The treatment should conform to the treatment of small cell lung cancer.

PMID- 19110303
TI  - The safety and efficacy of day 1 versus day 2 administration of pegfilgrastim in
      patients receiving myelosuppressive chemotherapy for gynecologic malignancies.
AB  - OBJECTIVE: Pegfilgrastim is indicated to decrease the incidence of febrile
      neutropenia in patients with gynecologic malignancies who are receiving
      myelosuppressive chemotherapy. We sought to compare the safety and efficacy of
      day 1 pegfilgrastim administration to day 2 administration in patients with
      gynecologic malignancies. METHODS: We retrospectively evaluated patients
      receiving both chemotherapy and pegfilgrastim from June 1, 2006 to August 31,
      2007 for a gynecologic malignancy. Abstracted data included patient demographics,
      pathology, blood counts, toxicity, and chemotherapy. After administration of
      chemotherapy, all patients either received 6 mg of pegfilgrastim subcutaneously
      on day 1 or day 2. RESULTS: 1226 administrations of pegfilgrastim in 230 patients
      were identified. 490 administrations of pegfilgrastim were given on day 1
      compared to 736 on day 2. 70% of patients had ovarian cancer with a median age of
      64 years (range 15-88). 79% of patients had stage III, IV, or recurrent disease
      and 67% were undergoing primary chemotherapy. The most common chemotherapy was
      docetaxel/carboplatin (53%) followed by paclitaxel/carboplatin (19%). The mean
      absolute neutrophil count (ANC) nadir was 4810/mm(3) in the day 1 cohort compared
      to 4212/mm(3) in the day 2 cohort (p=.004). The incidence of Grade 3/4
      neutropenia was similar in both groups (4.9% in day 1 vs. 5.7% in day 2; p=.63).
      Grade 3/4 febrile neutropenia was uncommon in both cohorts (0 episodes vs. 3
      episodes; p=.41). Treatment delays were similar in both cohorts (5.9% vs. 7.5%;
      p=.35). Dose modifications were also similar in both cohorts (2.8% vs. 5.3%;
      p=.06). CONCLUSION: Day 1 administration of pegfilgrastim is as effective as day
      2 administration in the prevention of neutropenia in patients with gynecologic
      malignancies. Treatment delays and dose modifications were not increased after
      day 1 administration of pegfilgrastim. Administering pegfilgrastim on day 1
      appears to be safe, effective, and convenient in selected patients receiving
      myelopsuppressive chemotherapy for gynecologic malignancies.

PMID- 19110304
TI  - Vitamin A metabolism is impaired in human ovarian cancer.
AB  - OBJECTIVES: We have previously reported that loss in expression of a protein
      considered critical for vitamin A homeostasis, cellular retinol-binding protein 1
      (CRBP1), is an early event in ovarian carcinogenesis. The aim of the present
      study was to determine if loss of vitamin A metabolism also occurs early in
      ovarian oncogenesis. METHODS: We assessed CRBP1 expression by
      immunohistochemistry in ovaries prophylactically removed from women with a
      genetic risk for ovarian cancer. Furthermore, we investigated the ability of
      normal, immortalized but nontumorigenic, and tumorigenic human ovarian epithelial
      cells to synthesize retinoic acid and retinaldehyde when challenged with a
      physiological dose of retinol, and determined expression levels of the retinoid
      related genes, RARalpha, RXRalpha, CRABP1, CRABP2, RALDH1 and RALDH2 in these
      cells. RESULTS: Immunohistochemistry revealed loss of CRBP1 expression in
      potentially preneoplastic lesions in prophylactic oophorectomies. HPLC analysis
      of vitamin A metabolism showed production of retinoic acid in four independent,
      normal human ovarian surface epithelial (HOSE) cell cultures upon exposure to
      retinol. However, only one of two SV40-immortalized HOSE cell lines made RA,
      while none of the ovarian carcinoma cell lines produced detectable RA due to
      complete loss of RALDH2. CONCLUSIONS: The impaired conversion of retinol to RA in
      ovarian cancer cells and decreased CRBP1 protein expression in prophylactic
      oophorectomies support our hypothesis that concomitant losses of vitamin A
      metabolism and CRBP1 expression contribute to ovarian oncogenesis.

PMID- 19110306
TI  - Cathepsin B protein levels in endometrial cancer: Potential value as a tumour
      biomarker.
AB  - OBJECTIVE: Lysosomal cysteine protease Cathepsin-B has been implicated in the
      progression of various human tumours. We examined Cathepsin-B protein levels in
      endometrial carcinoma patients-mainly post-menopausal-and investigated their
      possible association with clinical and pathological parameters in order to assess
      Cathepsin-B's significance as a potential tumour biomarker. METHODS: The indirect
      immunoperoxidase method was used for Cathepsin-B immunohistochemical staining of
      64 paraffin-embedded endometrial tumour tissues, having follow-up period of 18
      240 months. Steroid hormone receptors were measured as well. Tissue samples were
      staged following the FIGO criteria. RESULTS: Positive Cathepsin-B immunostaining
      was observed in 27 patients (42.2%) and was significantly associated with the
      FIGO stage of the disease (p=0.006), as well as cervical and stromal invasion
      (p=0.001 and p=0.037, respectively) and progesterone receptor status (p=0.027).
      Positive Cathepsin-B expression was also inversely related to Disease-free
      Survival (p=0.034) and Overall Survival (p=0.035) in univariate analysis, as well
      as in multivariate analysis (p=0.022 and p=0.035, respectively). CONCLUSION:
      Increased Cathepsin-B expression was found to be predictive of more aggressive
      tumour behaviour over time and can be regarded as an unfavourable and independent
      tumour marker for endometrial cancer patients with a long follow-up.

PMID- 19110307
TI  - The effect of insemination time and sperm dose on pregnancy rate using sex-sorted
      ram sperm.
AB  - The objective was to determine the optimum timing of insemination and minimum
      effective dose rate of sex-sorted ram sperm. Semen from three Merino rams was
      sorted into high purity X- and Y-chromosome bearing sperm populations. Ovulation
      was controlled in 732 Merino ewes using PMSG at progestagen pessary removal and
      GnRH 36h later. Sorted (S) and non-sorted (NS) doses of 1 or 15x10(6) motile,
      frozen-thawed sperm were inseminated laparoscopically at 50, 54, 58, 62, and 66h
      after progestagen withdrawal. An additional treatment dose of 0.5x10(6) S or NS
      sperm was inseminated at the 58h time point (n=60). Pregnancy was diagnosed by
      ultrasound at 60-62 d gestation. Both 1x10(6) and 15x10(6) sperm achieved similar
      pregnancy rates, regardless of sperm type, at 58h (S1: 46+/-9.4%; S15: 43+/-9.3%;
      NS1: 41+/-9.2%; NS15: 49+/-9.4%). However, pregnancy rates were lower (P<0.05)
      for doses of 1 than 15x10(6) sperm inseminated at 50 (15+/-6.3% vs. 36+/-9.1%),
      54 (14+/-4.4% vs. 55+/-7.3%), 62 (33+/-6.9% vs. 54+/-7.3%), and 66h (29+/-8.6%
      vs. 56+/-9.5%). There was no difference between S and NS sperm for inseminations
      with 0.5x10(6) motile sperm at 58h after PR (15+/-3.6% vs. 14+/-3.3%), nor with
      15x10(6) motile sperm at all insemination times (49+/-6.3% vs. 49+/-6.3%).
      However, fertility was higher for S than NS sperm at the 1x10(6) dose level (37+/
      6.1% and 16+/-4.0%). More than 90% of lambs born were of the predicted sex. We
      hypothesise that the sorting process selects a homogeneous, fertile sub
      population of sperm, removing those that are dead, damaged and morphologically
      abnormal.

PMID- 19110305
TI  - Markers of angiogenesis in high-risk, early-stage cervical cancer: A Gynecologic
      Oncology Group study.
AB  - OBJECTIVES: To determine whether markers of tumor angiogenesis were associated
      with progression-free survival (PFS) and overall survival (OS) in women with high
      risk, early-stage cervical cancer treated on a phase III trial. METHODS: One
      hundred seventy-three tumor specimens were analyzed by semi-quantitative
      immunohistochemical (IHC) staining for vascular endothelial growth factor (VEGF,
      pro-angiogenesis factor), thrombospondin-1 (TSP-1, anti-angiogenesis factor),
      CD31 (non-specific endothelial marker), and CD105 (tumor-specific endothelial
      marker). Tumoral histoscores (HS) were calculated for VEGF using the formula: [%
      cells positivex(intensity+1)]. TSP-1 specimens were categorized as negative or
      positive. CD31 and CD105 microvessel density (MVD) "hotspots" were counted in
      three 20x high-power fields. Associations between angiogenesis markers and
      survival were evaluated. RESULTS: TSP-1 expression was observed in 65% of cases
      while 66% expressed high VEGF (>or=200), 34% exhibited high CD31 (CD31>or=110)
      and 66% displayed high CD105 (CD105>or=28). In univariate analyses CD31 MVD, but
      not tumor TSP-1, was associated with improved PFS (HR=0.37; 95% CI=0.18-0.76;
      p=0.007) and OS (HR=0.37; 95% CI=0.17-0.79; p=0.010). After adjusting for
      prognostic clinical covariates, high CD31 MVD, but not TSP-1, VEGF or CD105 MVD,
      was an independent prognostic factor for PFS (HR=0.36; 95% CI=0.17-0.75; p=0.006)
      and OS (HR=0.36; 95% CI=0.17-0.79; p=0.010). CONCLUSIONS: Tumor angiogenesis
      measured by CD31 MVD is an independent prognostic factor for both PFS and OS in
      high-risk, early-stage cervical cancer. We hypothesize that this finding may be
      explained by improved treatment response in well-vascularized, well-oxygenated
      tumors.

PMID- 19110308
TI  - Stock and losses of trace metals from salt marsh plants.
AB  - Pools of Zn, Cu, Cd and Co in the leaf, stem and root tissues of Sarcocornia
      fruticosa, Sarcocornia perennis, Halimione portulacoides and Spartina maritima
      were analysed for a Tagus estuary (Portugal) salt marsh. Pools of Cu and Cd in
      the salt marsh were higher in spring/summer, indicating a net uptake of these
      metals during the growing season. Standing stocks of Zn, Cu, Cd and Co in the
      leaf and stem biomass of S. fruticosa, S. perennis and H. portulacoides showed a
      strong seasonal variation, with higher values recorded in autumn. The metal
      containing leaves and stems that shed in the autumn become metal-containing
      detritus. The amount of this material washed out from the total marsh area (200
      ha) was estimated as 68 kg of Zn, 8.2 kg of Cu, 13 kg of Co and 0.35 kg of Cd.
      The high tidal amplitude, a branched system of channels and semi-diurnal tidal
      cycle greatly favour the export of the organic detritus to adjoining marsh areas.

PMID- 19110309
TI  - Effects of incorporation of poly(gamma-glutamic acid) in chitosan/DNA complex
      nanoparticles on cellular uptake and transfection efficiency.
AB  - Chitosan (CS)/DNA complex nanoparticles (NPs) have been considered as a vector
      for gene delivery. Although advantageous for DNA packing and protection, CS-based
      complexes may lead to difficulties in DNA release once arriving at the site of
      action. In this study, an approach through modifying their internal structure by
      incorporating a negatively charged poly(gamma-glutamic acid) (gamma-PGA) in
      CS/DNA complexes (CS/DNA/gamma-PGA NPs) is reported. The analysis of small angle
      X-ray scattering results revealed that DNA and gamma-PGA formed complexes with CS
      separately to yield two types of domains, leading to the formation of "compounded
      NPs". With this internal structure, the compounded NPs might disintegrate into a
      number of even smaller sub-particles after cellular internalization, thus
      improving the dissociation capacity of CS and DNA. Consequently, after
      incorporating gamma-PGA in CS/DNA complexes, a significant increase in their
      transfection efficiency was found. Interestingly, in addition to improving the
      release of DNA intracellularly, the incorporation of gamma-PGA in CS/DNA
      complexes significantly enhanced their cellular uptake. We further demonstrated
      that besides a non-specific charged-mediated binding to cell membranes, there
      were specific trypsin-cleavable proteins involved in the internalization of
      CS/DNA/gamma-PGA NPs. The aforementioned results indicated that gamma-PGA played
      multiple important roles in enhancing the cellular uptake and transfection
      efficiency of CS/DNA/gamma-PGA NPs.

PMID- 19110310
TI  - Arsenic in groundwater: a threat to sustainable agriculture in South and South
      east Asia.
AB  - The problem of arsenic pollution of groundwater used for domestic water supplies
      is now well recognised in Bangladesh, India and some other countries of South and
      South-east Asia. However, it has recently become apparent that arsenic-polluted
      water used for irrigation is adding sufficient arsenic to soils and rice to pose
      serious threats to sustainable agricultural production in those countries and to
      the health and livelihoods of affected people. This paper reviews the nature of
      those threats, taking into account the natural sources of arsenic pollution,
      areas affected, factors influencing arsenic uptake by soils and plants, toxicity
      levels and the dietary risk to people consuming arsenic-contaminated rice.

PMID- 19110311
TI  - Involvement of intracellular signaling cascades in inflammatory responses in
      human intestinal epithelial cells following Vibrio cholerae infection.
AB  - Vibrio cholerae, the etiological agent of cholera, leads to the induction of host
      cell nuclear responses and the activation of proinflammatory cytokines in the
      cultured intestinal epithelial cells. However, the host cell signaling pathway
      leading to proinflammatory response is not explored. In this study, we
      demonstrated that V. cholerae infection on intestinal epithelial cells results in
      the activation of extracellular signal-regulated kinases1/2(ERK1/2) and p38 of
      the mitogen activated protein kinase (MAPK) family. V. cholerae induced
      intracellular pathways in Int407 cells leading to the activation of protein
      kinase A (PKA) and protein tyrosine kinase (PTK) in upstream of MAPK and nuclear
      factor-kappaB (NF-kappaB) pathway. Inhibitor study of Ca(2+) and phospholipase
      gamma (PLC-gamma) pathway suggested the possible involvement of Ca(2+) signaling
      in the V. cholerae pathogenesis. V. cholerae culture supernatants as also
      insertional mutants of ctxA, toxR and toxT genes modulate the activation of MAPK
      and NF-kappaB signaling pathways. MAPK and NF-kappaB signaling pathway activation
      were also modulated by adherence and motility of V. cholerae. Studies with
      inhibitor of NF-kappaB, MAPK, PTK, PKA, PKC, Ca(2+) and PLC pathways showed
      differential cytokine secretion in Int407 following V. cholerae infection.
      Therefore V. cholerae mediated induction of nuclear responses through signal
      transduction pathway and subsequent activation of proinflammatory cytokines in
      Int407 modulated by V. cholerae secretory factors, virulence, adhesion/motility
      which might explain some of its reactogenic mechanisms.

PMID- 19110312
TI  - Broad early immune response of porcine epithelial jejunal IPI-2I cells to
      Entamoeba histolytica.
AB  - Amoebiasis caused by Entamoebahistolytica triggers an acute inflammatory response
      at early stages of intestinal infection. The patho-physiological study of
      intestinal amoebiasis requires the development of powerful animal models. Swine
      provide robust model for human diseases and they could be used to study
      intestinal amoebiasis. Here, we introduce an in vitro model of swine intestinal
      epithelial cell (IPI-2I) co-cultured with E. histolytica. Intestinal epithelial
      cells (IECs) have crucial roles in sensing pathogens and initiating innate immune
      response, which qualitatively influence adaptive immune response against them.
      The contact between the two cells induces marked macroscopic lesions of IEC
      monolayer and striking alteration of the IPI-2I cell phenotype including
      blebbing, such as loss of attachment before to be phagocyte by the trophozoite.
      Increase in Lactate Dehydrogenase (LDH) levels in the culture supernatant of IECs
      was observed when ameba is present and could reflect the cellular cytotoxicity
      exerted by the parasite. Using quantitative real-time PCR, we identified the up
      regulation of cytokines/chemokines implicated in neutrophil chemoattraction and
      inflammation, such as CCL2, CCL20, CXCL2, CXCL3, GM-CSF, IL1 alpha, IL6 and IL8,
      in response to the parasite that can further regulate the immunoregulatory
      functions of the immune cells of the host. The study points a cardinal role of
      these pro-inflammatory compounds as central mediators in the interaction
      IECs/ameba and suggests mechanisms by which they coordinate intestinal immune
      response. This will focus future efforts on delineating the molecular and
      cellular mechanisms of other cell partners by the way of in vivo infection of
      swine.

PMID- 19110314
TI  - Decavanadate (V10 O28 6-) and oxovanadates: oxometalates with many biological
      activities.
AB  - The decameric vanadate species V(10)O(28)(6-), also referred to as decavanadate,
      impact proteins, lipid structures and cellular function, and show some effects in
      vivo on oxidative stress processes and other biological properties. The mode of
      action of decavanadate in many biochemical systems depends, at least in part, on
      the charge and size of the species and in some cases competes with the simpler
      oxovanadate species. The orange decavanadate that contains 10 vanadium atoms is a
      stable species for several days at neutral pH, but at higher pH immediately
      converts to the structurally and functionally distinct lower oxovanadates such as
      the monomer, dimer or tetramer. Although the biological effects of vanadium are
      generally assumed to derive from monomeric vanadate or the vanadyl cation, we
      show in this review that not all effects can be attributed to these simple
      oxovanadate forms. This topic has not previously been reviewed although
      background information is available [D.C. Crans, Comments Inorg. Chem. 16 (1994)
      35-76; M. Aureliano (Ed.), Vanadium Biochemistry, Research Signpost Publs.,
      Kerala, India, 2007]. In addition to pumps, channels and metabotropic receptors,
      lipid structures represent potential biological targets for decavanadate and some
      examples have been reported. Decavanadate interact with enzymes, polyphosphate,
      nucleotide and inositol 3-phosphate binding sites in the substrate domain or in
      an allosteric site, in a complex manner. In mitochondria, where vanadium was
      shown to accumulate following decavanadate in vivo administration, nM
      concentration of decavanadate induces membrane depolarization in addition to
      inhibiting oxygen consumption, suggesting that mitochondria may be potential
      targets for decameric toxicity. In vivo effects of decavanadate in piscine models
      demonstrated that antioxidant stress markers, lipid peroxidation and vanadium
      subcellular distribution is dependent upon whether or not the solutions
      administered contain decavanadate. The present review summarizes the reports on
      biological effects of decavanadate and highlights the importance of considering
      decavanadate in evaluations of the biological effects of vanadium.

PMID- 19110313
TI  - Vanadium compounds as therapeutic agents: some chemical and biochemical studies.
AB  - The behaviour of three vanadium(V) systems, namely the pyridinone (V(V)-dmpp),
      the salicylaldehyde (V(V)-salDPA) and the pyrimidinone (V(V)-MHCPE) complexes, is
      studied in aqueous solutions, under aerobic and physiological conditions using
      (51)V NMR, EPR and UV-Visible (UV-Vis) spectroscopies. The speciations for the
      V(V)-dmpp and V(V)-salDPA have been previously reported. In this work, the system
      V(V)-MHCPE is studied by pH-potentiometry and (51)V NMR. The results indicate
      that, at pH ca. 7, the main species present are (V(V)O(2))L(2) and (V(V)O(2))LH(
      1) (L=MHCPE(-)) and hydrolysis products, similar to those observed in aqueous
      solutions of V(V)-dmpp. The latter species is protonated as the pH decreases,
      originating (V(V)O(2))L and (V(V)O(2))LH. All the V(V)-species studied are stable
      in aqueous media with different compositions and at physiological pH, including
      the cell culture medium. The compounds were screened for their potential
      cytotoxic activity in two different cell lines. The toxic effects were found to
      be incubation time and concentration dependent and specific for each compound and
      type of cells. The HeLa tumor cells seem to be more sensitive to drug effects
      than the 3T3-L1 fibroblasts. According to the IC(50) values and the results on
      reversibility to drug effects, the V(V)-species resulting from the V(V)-MHCPE
      system show higher toxicity in the tumor cells than in non-tumor cells, which may
      indicate potential antitumor activity.

PMID- 19110315
TI  - Prevalence of C-terminal gag cleavage site mutations in HIV from therapy-naive
      patients.
AB  - OBJECTIVES: HIV protease - as well as gag cleavage site (CS) - mutations occur in
      HIV with PI resistance but little is known about the prevalence of CS mutations
      in drug-naive patients. PATIENTS AND METHODS: HIV samples (collected before 1997:
      n=94, after 1997: n=1617) from drug-naive patients were analysed in the C
      terminal gag and pol gene. Additionally, sequences from HIV Stanford database
      were included according to the collection date of the blood sample (before 1997:
      n=200, after 1997: n=375). RESULTS: Only CS mutations 431V and 452S were
      correlated with primary PI resistance in drug-naive HIV. Previously described
      therapy-associated CS mutations (431V/449F/449H/451T/452S/453A) were found in
      less than 0.5% of therapy-naive HIV without primary drug resistance and were
      totally absent in HIV isolates collected before 1997. The detection of 431V in
      the absence of PR mutations was significantly correlated with the presence of
      429K. The treatment-associated CS mutations (436R/437V/453L) were generally found
      in more than 1% of drug-naive HIV with differences between HIV subtypes. Natural
      polymorphisms were frequently found and also differed between HIV subtype B and
      non-B subtypes. CONCLUSIONS: The majority of therapy-associated CS mutations were
      rarely detected in drug-naive HIV, but can be found in the absence of protease
      mutations. Moreover, the prevalence of these CS mutations seemed to have
      increased in recent years. The presence of treatment-associated CS mutations in
      drug-naive patients might lower the genetic barrier of first-line therapies with
      protease inhibitors.

PMID- 19110316
TI  - Influence of two-stage weaning with subsequent transport on body weight, plasma
      lipid peroxidation, plasma selenium, and on leukocyte glutathione peroxidase and
      glutathione reductase activity in beef calves.
AB  - An experiment was conducted to assess the effects of two-stage weaning and
      subsequent transport on oxidative stress markers in calves. Thirty-six crossbred
      Angus steers (243+/-20.8 kg; 221+/-19.7 days) were allotted to control, fenceline
      (FL), and nose-clip (NC) weaning groups. Steers were weighed and blood samples
      were collected on days -7, 0 (pre-transit) and 7 surrounding transport.
      Leukocytes were analyzed for glutathione peroxidase and glutathione reductase
      activity, whereas malondialdehyde and Se were measured in plasma. Data were
      analyzed using PROC MIXED with the Tukey-Kramer adjustment applied post hoc. No
      treatment effects were detected for blood variables or weights. Glutathione
      peroxidase activity was not altered by time (P = 0.27). Glutathione reductase
      activity, Se, and malondialdehyde declined (P<0.001) from day -7 to 7 in all
      steers. Treatmentxdate interaction was detected for malondialdehyde (P<0.02).
      Control and FL steers gained weight (P<0.03), whereas NC steers did not gain
      weight between days -7 and 0 (P = 0.81). All weaning treatment groups gained
      weight between days 0 and 7 (P<0.05). Results suggest that two-stage weaning has
      little effect on examined markers of oxidative stress.

PMID- 19110317
TI  - Extracellular matrix, leukocyte migration and laminitis.
AB  - The structure and dynamic nature of extracellular matrix is discussed in the
      context of healthy and diseased tissues particularly the equine digital laminae.

PMID- 19110318
TI  - Equine laminitis: a journey to the dark side of venous.
AB  - Equine laminitis is a crippling condition that continues to defy repeated efforts
      to delineate the precise mechanisms involved and develop effective therapeutic
      strategies for use in the clinic. In this article, the possible role of
      dysfunction of the laminar vasculature is discussed, with particular emphasis on
      the venous side of the laminar microvasculature and the possible role(s) that
      metabolic syndrome and thrombosis may play in the dysfunction observed in the
      laminar microvasculature during the development of laminitis.

PMID- 19110319
TI  - Metabolic syndrome-From human organ disease to laminar failure in equids.
AB  - Obesity, insulin resistance, hyperinsulinemia and hypertriglyceridemia are
      components of an equine metabolic syndrome phenotype associated with increased
      laminitis risk in horses. Links between these conditions and laminitis must still
      be elucidated, but human medicine provides candidate mechanisms for future study,
      including inflammation associated with obesity, vascular compromise induced by
      insulin resistance, and endothelial dysfunction. Just as metabolic syndrome has
      been linked to cardiovascular disease in humans, studies are now required to
      determine the exact mechanisms responsible for the increased predisposition to
      laminitis observed in horses with equine metabolic syndrome.

PMID- 19110320
TI  - Characterization of the action of antipsychotic subtypes on valproate-induced
      chromatin remodeling.
AB  - Recent advances in schizophrenia (SZ) research indicate that the telencephalic
      gamma-aminobutyric acid (GABA)ergic neurotransmission deficit associated with
      this psychiatric disorder probably is mediated by the hypermethylation of the
      glutamic acid decarboxylase 67 (GAD(67)), reelin and other GABAergic promoters. A
      pharmacological strategy to reduce the hypermethylation of GABAergic promoters is
      to induce a DNA-cytosine demethylation by altering the chromatin remodeling with
      valproate (VPA). When co-administered with VPA, the clinical efficacy of atypical
      antipsychotics is enhanced. This prompted us to investigate whether this increase
      in drug efficacy is related to a modification of GABAergic-promoter methylation
      via chromatin remodeling. Our previous and present results strongly indicate that
      VPA facilitates chromatin remodeling when it is associated with clozapine or
      sulpiride but not with haloperidol or olanzapine. This remodeling might
      contribute to reelin- and GAD(67)-promoter demethylation and might reverse the
      GABAergic-gene-expression downregulation associated with SZ morbidity.

PMID- 19110321
TI  - Pharmacological basis for the role of curcumin in chronic diseases: an age-old
      spice with modern targets.
AB  - Curcumin (diferuloylmethane), a yellow pigment in the spice turmeric (also called
      curry powder), has been used for centuries as a treatment for inflammatory
      diseases. Extensive research within the past two decades has shown that curcumin
      mediates its anti-inflammatory effects through the downregulation of inflammatory
      transcription factors (such as nuclear factor kappaB), enzymes (such as
      cyclooxygenase 2 and 5 lipoxygenase) and cytokines (such as tumor necrosis
      factor, interleukin 1 and interleukin 6). Because of the crucial role of
      inflammation in most chronic diseases, the potential of curcumin has been
      examined in neoplastic, neurological, cardiovascular, pulmonary and metabolic
      diseases. The pharmacodynamics and pharmacokinetics of curcumin have been
      examined in animals and in humans. Various pharmacological aspects of curcumin in
      vitro and in vivo are discussed in detail here.

PMID- 19110322
TI  - A brief history of human brain mapping.
AB  - Human functional brain mapping as we presently know it began when the
      experimental strategies of cognitive psychology were combined with modern brain
      imaging techniques (first positron emission tomography and then functional
      magnetic resonance imaging) to examine how brain function supports mental
      activities. This marriage of disciplines and techniques galvanized the field of
      cognitive neuroscience, which has rapidly expanded to include a broad range of
      the social sciences in addition to basic scientists interested in the
      neurophysiology, cell biology and genetics of the imaging signals. Although much
      of this work has transpired over the past couple of decades, its roots can be
      traced back more than a century.

PMID- 19110323
TI  - The Pb-hyperaccumulator aquatic fern Salvinia minima Baker, responds to Pb(2+) by
      increasing phytochelatins via changes in SmPCS expression and in phytochelatin
      synthase activity.
AB  - The relationship between accumulation of Pb(2+) and the activation of chelation
      and metal sequestration mechanisms mediated by phytochelatins (PC) was analyzed
      in the Pb(2+) hyperaccumulator aquatic fern Salvinia minima, after exposure to
      40microM Pb(NO(3))(2). The tissue accumulation pattern of lead and the
      phytochelatin biosynthesis responses were analyzed in both, S. minima submerged
      root-like modified fronds (here named "roots"), and in its aerial leaf-like
      fronds ("leaves"). S. minima roots accumulated a significantly higher
      concentrations of Pb(+2) than leaves did. Accumulation of Pb(2+) in roots was bi
      phasic with a first uptake phase reached after 3h exposure and a second higher
      uptake phase reached after 24h exposure. In leaves, a single delayed, smaller
      uptake phase was attained only after 9h of exposure. In roots lead accumulation
      correlated with an increased phytochelatin synthase (PCS) activity and an
      enhanced PC production. A higher proportion of polymerized PC(4) was observed in
      both tissues of exposed S. minima plants relative to unexposed ones, although a
      higher concentration of PC(4) was found in roots than in leaves. PCS activity and
      Pb(2+) accumulation was also higher in roots than in leaves. The expression
      levels of the S. minima PCS gene (SmPCS), in response to Pb(2+) treatment, were
      also evaluated. In S. minima leaves, the accumulation of Pb(2+) correlated with a
      marked increase in expression of SmPCS, suggesting a transcriptional regulation
      in the PCS activation and PC accumulation in this S. minima tissue. However, in
      roots, the basal expression of SmPCS was down-regulated after Pb(2+) treatment.
      This fact did not correlate with the later but strong increase in both, PCS
      activity and PC production; suggesting that the PC biosynthesis activation in S.
      minima roots occurs only by post-translational activation of PCS. Taken together,
      our data suggest that the accumulation of PC in S. minima is a direct response to
      Pb(2+) accumulation, and phytochelatins do participate as one of the mechanism to
      cope with Pb(2+) of this Pb-hyperaccumulator aquatic fern.

PMID- 19110324
TI  - Developmental mechanisms of arsenite toxicity in zebrafish (Danio rerio) embryos.
AB  - Arsenic usually accumulates in soil, water and airborne particles, from which it
      is taken up by various organisms. Exposure to arsenic through food and drinking
      water is a major public health problem affecting some countries. At present there
      are limited laboratory data on the effects of arsenic exposure on early embryonic
      development and the mechanisms behind its toxicity. In this study, we used
      zebrafish as a model system to investigate the effects of arsenite on early
      development. Zebrafish embryos were exposed to a range of sodium arsenite
      concentrations (0-10.0mM) between 4 and 120h post-fertilization (hpf). Survival
      and early development of the embryos were not obviously influenced by arsenite
      concentrations below 0.5mM. However, embryos exposed to higher concentrations
      (0.5-10.0mM) displayed reduced survival and abnormal development including
      delayed hatching, retarded growth and changed morphology. Alterations in neural
      development included weak tactile responses to light (2.0-5.0mM, 30hpf),
      malformation of the spinal cord and disordered motor axon projections (2.0mM,
      48hpf). Abnormal cardiac function was observed as bradycardia (0.5-2.0mM, 60hpf)
      and altered ventricular shape (2.0mM, 48hpf). Furthermore, altered cell
      proliferation (2.0mM, 24hpf) and apoptosis status (2.0mM, 24 and 48hpf), as well
      as abnormal genomic DNA methylation patterning (2.0mM, 24 and 48hpf) were
      detected in the arsenite-treated embryos. All of these indicate a possible
      relationship between arsenic exposure and developmental failure in early
      embryogenesis. Our studies suggest that the negative effects of arsenic on
      vertebrate embryogenesis are substantial.

PMID- 19110325
TI  - Hemodynamic performance evaluation of TTK Chitra heart valve prosthesis in the
      aortic position using Doppler echocardiography.

PMID- 19110327
TI  - Prognostic implications of stress-induced transient ischemic dilation of the left
      ventricle in patients with systolic dysfunction and fixed perfusion defects.
AB  - PURPOSE: To verify whether stress-induced transient ischemic dilation (TID) of
      the left ventricle may help refine prognostic assessment of patients with resting
      systolic dysfunction and fixed perfusion defects. METHODS: Two hundred seventy
      patients with resting ejection fraction <or=50% and fixed perfusion defects on
      exercise (n=180) or dipyridamole (n=90) ECG-gated single-photon emission computed
      tomography (SPECT) were followed-up for the combined endpoint of death, acute
      coronary syndrome, and clinically-driven revascularization. The TID ratio was
      defined as the ratio of LV volumes at stress and rest. RESULTS: During a median
      time of 24 months, 47 events (10 deaths, 20 acute coronary syndromes and 17
      revascularization) were observed. After adjusting for clinical and stress testing
      variables, the unfeasible exercise test [hazard ratio (HR) 1.82, 95% confidence
      interval (CI) 1.02, 3.24] and the highest quartile of TID ratio [HR 1.93, 95% CI
      1.05, 3.54] were the only independent predictors of outcome. The highest quartile
      of TID ratio was associated to significantly lower percent of event-free
      survival. CONCLUSIONS: Left ventricular TID ratio helps refine outcome prediction
      in patients with resting systolic dysfunction and fixed perfusion defects, thus
      reducing risk of a false negative result.

PMID- 19110328
TI  - Reproducibility of echocardiographic measurements of epicardial fat thickness.

PMID- 19110329
TI  - Plants disarm soil: engineering plants for the phytoremediation of explosives.
AB  - Explosives are toxic, recalcitrant to degradation and contaminate large areas of
      land and ground water. Remediation of these synthetic compounds is difficult and
      an enormous logistical task. Phytoremediation is a technique that offers an
      environmentally friendly, low-cost alternative to current remediation techniques;
      however, this approach is hindered by the low inherent metabolic abilities of
      plants towards these xenobiotic compounds and the phytotoxicity of these
      compounds. As a result of recent advances in our knowledge of the biochemistry
      underlying endogenous plant detoxification systems and the use of genetic
      engineering to combine bacterial explosives-detoxifying genes with the
      phytoremediatory benefits of plants, this technology is now poised for testing in
      the field and in a wider range of plants, such as poplar and perennial grasses.

PMID- 19110331
TI  - Analysis and simulation of creativity learning by means of artificial neural
      networks.
AB  - The paper presents a new neural network approach for analysis and simulation of
      creative behavior. The used concept of Dynamically Controlled Neural Gas (DyCoNG)
      entails a combination of Dynamically Controlled Network [Perl, J. (2004a). A
      neural network approach to movement pattern analysis. Human Movement Science,23,
      605-620] and Growing Neural Gas (Fritzke, 1995) by quality neurons. A quality
      neuron reflects the rareness of a piece of information and therefore can measure
      the originality of a recorded activity that was assigned to the neuron during the
      network training. The DyCoNG approach was validated using data from a
      longitudinal field-based study. The creative behavior of 42 participants in
      standardized test situations was tested in a creative training program lasting
      six months. The results from the DyCoNG-based simulation show that the network is
      able to separate main process types and reproduce recorded creative learning
      processes by means of simulation. The results are discussed in connection with
      practical implications in team sports and with a view to future investigations.

PMID- 19110330
TI  - Towards a 'universal' nucleant for protein crystallization.
AB  - The expression 'crystal clear' stems from the science of crystallography, which
      determines the detailed atomic structures of materials by exposing crystals to X
      rays. Protein structures are pivotal to the success of rational drug design and
      other biotechnology applications; however, obtaining high quality crystals poses
      a major problem to progress. Nucleation is the first step that determines the
      entire crystallization process, thus control of crystal nucleation would tackle
      the problem at its conception. A search for a 'universal' nucleant, a substance
      that can induce nucleation of any protein, is therefore on-going. We report the
      advances that have been made in this area, highlighting the success of especially
      engineered as well as naturally structured surfaces.

PMID- 19110332
TI  - Catching fly balls: a simulation study of the Chapman strategy.
AB  - Chapman [Chapman, S. (1968). Catching a baseball. American Journal of Physics,
      36, 868-870] showed that a catcher may be guided to the landing spot of a fly
      ball by zeroing out its optical acceleration. Subsequently, various studies have
      provided evidence for what is now known as the Chapman strategy. However, in
      those studies the catcher's own acceleration and the visuo-motor delay were
      ignored. This raises the question whether the Chapman strategy still provides an
      accurate description if those factors are taken into account. To address this
      question, we implemented the Chapman strategy in a forward dynamical model of the
      catcher's locomotion in relation to the ball's actual trajectory. Numerical
      simulations of the model revealed that catching performance was still successful
      under a broad range of ball trajectories. Furthermore, the model simulations
      largely reproduced the real running paths reported by McLeod and Dienes [McLeod,
      P., & Dienes, Z. (1996). Do fielders know where to go to catch the ball or only
      how to get there? Journal of Experimental Psychology: Human Perception and
      performance, 22, 531-543]. However, the simulations also revealed that real
      running paths exhibit some detailed characteristics that appear to be
      irreconcilable with the Chapman strategy.

PMID- 19110333
TI  - A polyphasic approach to the identification of aflatoxigenic and non
      aflatoxigenic strains of Aspergillus Section Flavi isolated from Portuguese
      almonds.
AB  - A polyphasic approach consisting of morphological, chemical and molecular
      characterization was applied to 31 isolates of Aspergillus Section Flavi
      originating from Portuguese almonds, with the aim of characterizing and
      identifying aflatoxigenic and non-aflatoxigenic strains. On the basis of
      morphological characters (mainly colony color on Czapek-Dox agar and conidia
      morphology), we found two distinct groups among the population under study: 18
      isolates (58%) had dark-green colonies and rough conidia, and were classified as
      Aspergillus parasiticus; the remaining 13 isolates (42%) had yellow-green
      colonies and smooth to finely rough globose conidia, and were classified as
      Aspergillus flavus. Chemical characterization involved the screening of the
      isolates for aflatoxins B (AFB) and G (AFG), and also for cyclopiazonic acid
      (CPA), by HPLC with fluorescence and UV detection, respectively. All A.
      parasiticus isolates were strong AFB and AFG producers, but no CPA production was
      detected, showing a consistent mycotoxigenic pattern. The A. flavus isolates
      showed to be more diversified, with 77% being atoxigenic, whereas 15% produced
      CPA and low levels of AFB and 8% produced the 3 groups of mycotoxins. Aflatoxin
      production was also screened on Coconut Agar Medium (CAM), and the results were
      consistent with the HPLC analysis. Sclerotia production showed no correlation to
      aflatoxigenicity. Molecularly, two genes of the aflatoxin biosynthetic pathway,
      aflD (=nor1) and aflQ (=ord1=ordA) were tested for presence and expression (by
      PCR and RT-PCR, respectively). The presence of both genes did not correlate with
      aflatoxigenicity. aflD expression was not considered a good marker for
      differentiating aflatoxigenic from non-aflatoxigenic isolates, but aflQ showed a
      good correlation between expression and aflatoxin-production ability.

PMID- 19110334
TI  - Upregulated IL-18 expression in type 2 diabetic subjects with nephropathy: TGF
      beta1 enhanced IL-18 expression in human renal proximal tubular epithelial cells.
AB  - AIM: In order to clarify the importance of Interleukin (IL)-18 in the development
      of diabetic nephropathy (DN), we evaluated the expressions of IL-18 in diabetic
      kidney. METHODS: We performed immmunohistochemical analysis of IL-18 and IL-18
      receptor (IL-18 R) in human kidney tissue derived from 12 subjects with type 2
      diabetes and overt nephropathy, and compared with those in 7 subjects with
      minimal change nephrotic syndrome (MCNS). In addition, we examined the regulation
      of IL-18 expression using human renal proximal tubular epithelial cells (HRPTECs)
      in culture. RESULTS: IL-18 expression in tubular cells was observed in higher
      rate (83%) in patients with diabetes, whereas one positive specimen (14.3%) for
      IL-18 in patients with MCNS. In contrast, IL-18 R was expressed in glomerular
      mesangial cells and endothelial cells as well as tubular cells, similarly in
      almost of both groups. Exposure to transforming growth factor beta (TGF-beta(1))
      led to two-fold increase in IL-18 gene expression in HRPTECs, and mitogen
      activated protein kinases (MAPK) inhibitors abolished TGF-beta(1)-induced IL-18
      mRNA expression. Western blot analysis showed the IL-18 protein in HRPTECs.
      CONCLUSION: The present data indicate that IL-18 is overexpressed in human
      tubular epithelial cells in diabetic nephropathy, probably through the activation
      of MAPK pathways induced by TGF-beta(1).

PMID- 19110335
TI  - Influence of hemoglobin E on measurement of hemoglobin A1c by immunoassays.
AB  - BACKGROUND: Many assays used for HbA1c measurement can be interfered by
      hemoglobin variants. Hemoglobin E is one of the most common variant. Effect of
      HbE on high performance liquid chromatography was widely reported but not on
      immunoassay. OBJECTIVE: To determine the effect of hemoglobin E on HbA1c values
      by immunoassay methods. MATERIAL AND METHODS: Two immunoassays were used for
      measurement of HbA1c in samples with hemoglobin type as A2A (normal controls,
      n=60), EA (heterozygous hemoglobin E, n=151), and EE (homozygous hemoglobin E,
      n=43). Results within each assay and each hemoglobin typing group were compared.
      Mann-Whitney U test, Pearson's correlation and linear regression analysis were
      used. RESULTS: There were significant differences of HbA1c values between normal
      controls and hemoglobin E-contained samples. Correlation between two assays was
      worse in the presence of hemoglobin E comparing to normal controls. CONCLUSION:
      Hemoglobin E can affect the immunoassays used for HbA1c measurement. Further
      studies are needed to understand the mechanism of interference.

PMID- 19110336
TI  - Mitochondrial DNA mutations and aging: devils in the details?
AB  - Although several lines of evidence support a role for accumulating somatic
      mitochondrial DNA (mtDNA) mutations in the etiology of aging, it remains unclear
      if they are a major cause of age-related deterioration and death. Mouse models
      that harbor elevated mtDNA mutation frequencies age prematurely; these findings
      were thought to provide conclusive evidence for a causal role of such mutations
      in aging. Yet, the presence of several conflicting reports has sparked
      controversy in the field and this is further aggravated by discrepancies in the
      estimates of mtDNA mutant fractions, which disagree by orders of magnitude. Here,
      we briefly review the evidence and some of the unresolved questions surrounding a
      causative role for accumulating mtDNA mutations in aging.

PMID- 19110338
TI  - Sampling bias resulting from animal personality.

PMID- 19110337
TI  - Erlotinib after Gefitinib failure in female never-smoker Asian patients with
      pulmonary adenocarcinoma.
AB  - The activity of erlotinib after gefitinib failure in non-small cell lung cancer
      patients with all four favorable clinical factors including female, never smoker,
      Asian, and adenocarcinoma histology for tyrosine kinase inhibitors (TKIs) is not
      well known. Treatment efficacy of erlotinib (150mg daily) after progression on
      gefitinib (250mg daily) was analyzed in patients exhibiting the four clinically
      favorable factors. Sixteen consecutive female, never smoker, Korean (Asian),
      adenocarcinoma patients who received erlotinib after gefitinib failure were
      analyzed. The disease control rate for gefitinib was 68.8% (95% CI, 0.44-0.86)
      while the disease control rate for erlotinib following gefitinib failure was
      25.0% (95% CI, 0.10-0.50) comprised of one partial response and three stable
      disease patients. The median progression free survival was 6.3 months for
      gefitinib treatment and 1.7 months for erlotinib treatment following gefitinib
      failure. The efficacy of erlotinib after progression on gefitinib is
      unsatisfactory in patients with four favorable clinical factors for TKIs. Novel
      treatment approaches such as the use of irreversible TKIs or anti-cMET agents for
      those patients are warranted.

PMID- 19110339
TI  - Simulating the evolution of an ethanol and gasoline source zone within the
      capillary fringe.
AB  - Blending of ethanol into gasoline as a fuel oxygenate has created the scenario
      where inadvertent releases of E95 into soil previously contaminated by gasoline
      may remobilize these pre-existing NAPLs and lead to higher dissolved hydrocarbon
      (BTEX) concentrations in groundwater. We contribute to the development of a risk
      based corrective action framework addressing this issue by conducting two
      laboratory experiments involving the release of ethanol into a gasoline source
      zone established in the capillary fringe. We then develop and apply the numerical
      model CompFlow Bio to replicate three specific experimental observations: (1)
      depression of the capillary fringe by the addition of the gasoline fuel mixture
      due to a reduction in the surface tension between the gas and liquid phases, (2)
      further depression of the capillary fringe by the addition of ethanol, and (3)
      remobilization of the gasoline fuel mixture LNAPL source zone due to the
      cosolvent behaviour of ethanol in the presence of an aqueous phase, as well as a
      reduction in the interfacial tension between the aqueous/non-aqueous phases due
      to ethanol. While the simulated collapse of the capillary fringe was not as
      extensive as that which was observed, the simulated and observed remobilized non
      aqueous phase distributions were in agreement following ethanol injection.
      Specifically, injection of ethanol caused the non-aqueous phase to advect
      downwards toward the water table as the capillary fringe continued to collapse,
      finally collecting on top of the water table in a significantly reduced area
      exhibiting higher saturations than observed prior to ethanol injection.
      Surprisingly, the simulated ethanol and gasoline aqueous phase plumes were
      uniform despite the redistribution of the source zone. Dissolution of gasoline
      into the aqueous phase was dramatically increased due to the cosolvency effect of
      ethanol on the non-aqueous phase source zone. We advocate further experimental
      studies focusing on eliminating data gaps identified here, as well as field-scale
      experiments to address issues associated with ethanol-BTEX biodegradation and
      sorption within the development of a risk-based corrective action framework.

PMID- 19110340
TI  - Metabolic effects of glyphosate change the capacity of maize culture to
      regenerate plants.
AB  - Since the presence of glyphosate in maize tissue cultures of proprietary line L2
      was very detrimental to plant regeneration, we determined metabolic changes
      associated with the glyphosate effects on plant regeneration in maize cultures.
      The polar fraction composition and soluble and cell-wall-bound phenolics were
      analyzed in the regenerable (R) and non-regenerable (NR) calluses of maize line
      L2. The tissues with high regeneration capacity had low sugar and 4-aminobutyric
      acid (GABA) concentrations and increased concentrations of most amino acids,
      polyamines and indole-3-butenol in the soluble polar fraction and higher ferulic
      acid/coumaric acid and ferulic acid/diferulic acid ratios and higher levels of
      the predominant G (guaiacyl) units in the cell wall fraction compared with NR
      calluses as was found before with H99 and HiII maize R and NR tissues, indicating
      an association of these metabolites with the capacity of maize cultured tissue to
      regenerate plants. We also found that di-coumaroyl spermidine and coumaroyl
      feruoyl spermidine are present in the soluble fraction of L2 R tissues and are
      practically absent in NR tissues. However, we did not see such differences in
      HiII and H99 samples, which indicate that these are genotypic features not
      related to the capacity to regenerate plants in maize tissue cultures. Glyphosate
      treatment caused the accumulation of shikimic and quinic acids (not detected in
      untreated samples) in R and NR calluses (with higher levels found in R tissues)
      and also decreased the FA/diFA ratio in cell wall phenolics, polyamine and amino
      acid levels, and increased sugar concentrations in the R L2 tissues, indicating a
      metabolic shift of R callus to NR tissues.

PMID- 19110341
TI  - GRIND-based 3D-QSAR and CoMFA to investigate topics dominated by hydrophobic
      interactions: the case of hERG K+ channel blockers.
AB  - The study compares GRIND-based 3D-QSAR and CoMFA [A. Cavalli, E. Poluzzi, F. De
      Ponti, M. Recanatini, J. Med. Chem, 45(2002), 3844-53] to investigate a
      biological topic dominated by hydrophobic interactions, e.g. hERG K(+) channel
      blocking activity. As expected, models are found by both methods and there is a
      fine agreement between statistical and graphical results as well. However, a
      closer inspection revealed that failures in the prediction of hERG blocking
      activity for lipophilic compounds were registered for both methods. The study
      explores the reasons for these failures which are strongly dependent on the
      chosen method, and gives some suggestions to handle with these topics.

PMID- 19110342
TI  - Exploring QSAR and QAAR for inhibitors of cytochrome P450 2A6 and 2A5 enzymes
      using GFA and G/PLS techniques.
AB  - A series of naphthalene and non-naphthalene derivatives (n=42) having cytochrome
      P450 2A6 and 2A5 inhibitory activities, reported by Rahnasto et al., were
      subjected to QSAR and QAAR studies. The analyses were performed using electronic,
      spatial, shape and thermodynamic descriptors to develop quantitative models for
      prediction of the inhibitory activities and to explore importance of different
      descriptors for the responses. The data set was divided into training and test
      sets (with test set size being approximately 25% of the full data set size) based
      on K-means clustering applied on the standardized descriptor matrix. 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 and prediction (both internal and external) qualities although
      different equations varied in quality in a wide range (R(2): 0.561-0.898,
      R(a)(2): 0.508-0.870, Q(2): 0.495-0.814, R(pred)(2): 0.615-0.914, r(2): 0.679
      0.905, r(0)(2): 0.639-0.904, r(m)(2): 0.494-0.876). In the case of CYP2A5
      inhibition, the GFA derived QSAR model is better than the G/PLS derived model
      considering both internal and external validations. In the case of CYP2A6
      inhibitory potency data, the GFA derived QSAR model is better than the G/PLS
      model considering internal validation whereas the latter is better in external
      validation (which is more important) than the former. The model development
      process was subjected to randomization test at 90% confidence level by taking
      into account the whole pool of descriptors, while the developed models were also
      subjected to randomization test (99% confidence level) for validation. Based on
      the randomization test results, GFA models are found to be superior to the G/PLS
      models. Among the parameters, which were found important in modeling both the
      responses, were different Jurs descriptors, electronic descriptors (like Sr,
      Apol), steric descriptors (like shadow indices, Molref), shape descriptors (like
      COSV, Fo) and lipophilicity descriptors. This indicates that the CYP2A5 and
      CYP2A6 inhibition of these compounds is related to charge distribution, surface
      area, electronic, hydrophobic and spatial properties of the molecules.

PMID- 19110343
TI  - Design and synthesis of new N-(fluorenyl-9-methoxycarbonyl) (Fmoc)-dipeptides as
      anti-inflammatory agents.
AB  - Twenty-four new dipeptide analogs (1-24) of aurantiamide acetate were designed,
      synthesized, and assayed for effects on superoxide anion generation and elastase
      release by human neutrophils in response to fMLP/CB. Among them, seven N
      (fluorenyl-9-methoxycarbonyl) (Fmoc)-dipeptides (6, 9, 12, 14, 17, 18 and 20)
      showed potent inhibitory effects. Compounds 9 and 18 showed the most selective
      effects against human neutrophil elastase release, with IC(50) values of 0.8+/
      0.1 and 1.7+/-0.6muM, respectively, and were 130-fold more potent than
      phenylmethylsulfonyl fluoride (PMSF), the positive control, in this anti
      inflammatory assay. These two compounds could be developed as new lead anti
      inflammatory agents.

PMID- 19110344
TI  - [Septic arthritis of thoracic facet joint].
AB  - Septic arthritis of the facet joint is a rare condition. We report a case of
      septic arthritis of both a thoracic facet joint and a wrist. Clinical
      manifestations were consistent with a spondylodiscitis. Magnetic resonance
      imaging of the spine demonstrated infection of facet joints of T1 and T2. A
      surgical biopsy of the wrist isolated a type B streptococcus. The same organism
      was found in urine culture. The patient had an uneventful recovery on
      antibiotics.

PMID- 19110345
TI  - Nutritional status in hospitalized elderly patients with mild cognitive
      impairment.
AB  - BACKGROUND & AIMS: Malnutrition is prevalent in hospitalized elderly people
      leading to complications including cognitive deficit. However, the relationship
      between the nutritional status and the preclinical phase of dementia in the
      elderly is still unclear. The aim of this study was to evaluate the prevalence of
      malnutrition in older patients with mild cognitive impairment. METHODS: A total
      of 623 hospitalized elderly patients underwent the comprehensive geriatric
      assessment to evaluate medical, cognitive, affective and social aspects.
      Nutritional status was assessed by using the mini-nutritional assessment. The
      cognitive function was categorized into three levels -- normal cognition, mild
      cognitive impairment and dementia -- according to the neuropsychological
      evaluation. RESULTS: According to the mini-nutritional assessment classification,
      18% of the sample study was assessed as well nourished, 58% at risk of
      malnutrition and 24% as malnourished. Patients with mild cognitive impairment and
      dementia had significantly lower frequency of well nourished and higher frequency
      of at risk of malnutrition or malnourished than patients with normal cognition.
      CONCLUSIONS: Malnutrition is prevalent in hospitalized elderly patients with
      cognitive deficit, even in those with mild cognitive impairment. It remains to be
      demonstrated whether improvement in nutritional status may delay progression to
      dementia in these patients.

PMID- 19110346
TI  - Radioecological consequences of a potential accident during transport of spent
      nuclear fuel along an Arctic coastline.
AB  - This article presents results pertaining to a risk assessment of the potential
      consequences of a hypothetical accident occurring during the transportation by
      ship of spent nuclear fuel (SNF) along an Arctic coastline. The findings are
      based on modelling of potential releases of radionuclides, radionuclide transport
      and uptake in the marine environment. Modelling work has been done using a
      revised box model developed at the Norwegian Radiation Protection Authority.
      Evaluation of the radioecological consequences of a potential accident in the
      southern part of the Norwegian Current has been made on the basis of calculated
      collective dose to man, individual doses for the critical group, concentrations
      of radionuclides in seafood and doses to marine organisms. The results of the
      calculations indicate a large variability in the investigated parameters above
      mentioned. On the basis of the calculated parameters the maximum total activity
      ("accepted accident activity") in the ship, when the parameters that describe the
      consequences after the examined potential accident are still in agreement with
      the recommendations and criterions for protection of the human population and the
      environment, has been evaluated.

PMID- 19110347
TI  - Beryllium-7 atmospheric deposition and sediment inventories in the Neponset River
      estuary, Massachusetts, USA.
AB  - Measured monthly atmospheric depositional fluxes of cosmogenically produced (7)Be
      ranged from 1 to 67 mBq/cm(2) in Boston, Massachusetts between September 2000 and
      August 2007. These fluxes exhibited seasonality and supported a decay-corrected
      (7)Be atmospheric depositional running inventory that ranged from 36 to 144
      mBq/cm(2). Annual (7)Be deposition exhibited an increasing trend that may reflect
      a general decrease in solar activity and a general increase in precipitation over
      the 7-year sampling period. To investigate short-term sediment dynamics and
      accumulation patterns in the Neponset River estuary, we collected six sediment
      cores in July 2006 and measured (7)Be sediment inventories ranging from 48 to 546
      mBq/cm(2) Comparisons of these sediment inventories with the (7)Be running
      inventory from atmospheric deposition (101 mBq/cm(2)) at the time of core
      collection indicated a large degree of spatial heterogeneity in sediment
      accumulation patterns and its potential use as a tool for assessing the impacts
      of environmental restoration activities in estuarine environments.

PMID- 19110348
TI  - Monitoring organic contaminants in eggs of glaucous and glaucous-winged gulls
      (Larus hyperboreus and Larus glaucescens) from Alaska.
AB  - Gull eggs have been used to monitor contaminants in many parts of the world. The
      Seabird Tissue Archival and Monitoring Project (STAMP) is a long-term program
      designed to track trends in pollutants in northern marine environments using
      seabird eggs. Glaucous and glaucous-winged gull (Larus hyperboreus and Larus
      glaucescens) eggs collected in 2005 from seven Alaskan colonies were analyzed for
      organic contaminants. Concentrations ranged from below detection limits to 322 ng
      g(-1) wet mass in one egg for 4,4'-DDE and differed among the samples collected
      in the Gulf of Alaska and Bering and Chukchi Seas. Chick growth and survival
      rates may be affected by the contaminant levels found in the eggs, but the eggs
      should be safe for human consumption if they are eaten in small quantities. STAMP
      plans to continue collecting and banking gull eggs for future real-time and
      retrospective analyses.

PMID- 19110349
TI  - Greenhouse gas production and efficiency of planted and artificially aerated
      constructed wetlands.
AB  - Greenhouse gas (GHG) emissions by constructed wetlands (CWs) could mitigate the
      environmental benefits of nutrient removal in these man-made ecosystems. We
      studied the effect of 3 different macrophyte species and artificial aeration on
      the rates of nitrous oxide (N(2)O), carbon dioxide (CO(2)) and methane (CH(4))
      production in CW mesocosms over three seasons. CW emitted 2-10 times more GHG
      than natural wetlands. Overall, CH(4) was the most important GHG emitted in
      unplanted treatments. Oxygen availability through artificial aeration reduced
      CH(4) fluxes. Plant presence also decreased CH(4) fluxes but favoured CO(2)
      production. Nitrous oxide had a minor contribution to global warming potential
      (GWP<15%). The introduction of oxygen through artificial aeration combined with
      plant presence, particularly Typha angustifolia, had the overall best performance
      among the treatments tested in this study, including lowest GWP, greatest
      nutrient removal, and best hydraulic properties.

PMID- 19110350
TI  - Sandhopper solar orientation as a behavioural biomarker of trace metals
      contamination.
AB  - Although many studies have focused on trace metals accumulation, investigations
      of talitrid amphipods as biomarkers are rare. This study explores the possibility
      of using the solar orientation capacity of Talitrus saltator as a behavioural
      marker of exposure to two essential (Cu and Zn) and two non-essential (Cd and Hg)
      metals. LC(50) analyses performed before the solar orientation tests showed that
      the 72 h LC(50) for Hg was 0.02 ppm while the 96 h LC(50) values for Cu, Cd and
      Zn were 13.28 ppm, 27.66 ppm, and 62.74 ppm, respectively. The presence of metals
      in seawater affects the solar orientation capacity of T. saltator in a
      concentration-dependent manner and according to the toxicity ranking of the
      metals (Hg > Cu > Cd > Zn). Therefore, the solar orientation capacity of T.
      saltator seems to be a promising behavioural marker for exposure to trace metals.

PMID- 19110351
TI  - Behaviour of damselfly larvae (Enallagma cyathigerum) (Insecta, Odonata) after
      long-term exposure to PFOS.
AB  - Perfluorooctane sulfonic acid (PFOS) is a persistent and ubiquitous environmental
      contaminant that has been detected in organisms worldwide. Here, we evaluate
      whether long-term (1 and 4 months) exposure to PFOS contamination affects the
      behavioural performance of freshwater larvae of the damselfly Enallagma
      cyathigerum (Insecta: Odonata). Our results show reduced behavioural performance
      with increasing PFOS concentration. In 1 month exposed larvae, no observed effect
      concentrations (NOECs) were 100 microg/L for general activity. In 4 months
      exposed larvae, NOECs were 10 microg/L, for each behavioural trait, except
      swimming acceleration of male larvae where the NOEC was 100 microg/L. When faced
      with PFOS concentrations above the NOEC, E. cyathigerum larvae were less active,
      less capable to escape a simulated predator attack and less efficient in
      foraging. Together, our results show that damselfly larvae suffer reduced
      survival-related behavioural performance.

PMID- 19110352
TI  - Selenium assimilation and loss by an insect predator and its relationship to Se
      subcellular partitioning in two prey types.
AB  - Subcellular selenium (Se) distributions in the oligochaete Tubifex tubifex and in
      the insect Chironomus riparius did not vary with Se exposure duration, which was
      consistent with the observations that the duration of prey Se exposure had little
      influence on either Se assimilation or loss by a predatory insect (the alderfly
      Sialis velata). However, these two prey types differed in how Se was distributed
      in their cells. Overall, the predator assimilated a mean of 66% of the Se present
      in its prey, which was similar to the mean percentage of Se in prey cells (62%)
      that was theoretically available for uptake (that is, Se in the protein and
      organelle fractions). Likewise, data for cadmium, nickel and thallium suggest
      that predictions of trace element transfer between prey and predator are
      facilitated by considering the subcellular partitioning of these contaminants in
      prey cells.

PMID- 19110354
TI  - Accumulation features and temporal trends of PCDDs, PCDFs and PCBs in Baikal
      seals (Pusa sibirica).
AB  - This study investigated the accumulation features and temporal trends of PCDD/Fs,
      dioxin-like PCBs (DL-PCBs) and non-dioxin-like PCBs (NDL-PCBs) in the blubber of
      Baikal seals collected in 1992 and 2005. DL-PCBs (480-3600ng/g) and NDL-PCBs (980
      35,000ng/g) were dominant contaminants. Concentrations of PCDDs and PCBs in males
      were significantly higher than in females. In males, age-dependent accumulation
      was observed for PCDDs, mono-ortho PCBs and NDL-PCBs. PCDFs and non-ortho PCBs
      showed no such trends, implying that exposure of seals to these contaminants has
      been decreasing in recent years. No decreasing temporal trend was observed for
      PCDDs, mono-ortho PCBs and NDL-PCBs, suggesting that Baikal seals are still
      exposed to PCDDs and PCBs. TEQs of PCDDs and mono-ortho PCBs in seals collected
      in 2005 accounted for 62-77% of total TEQs. The TEQ levels in 40% of the
      specimens exceeded the threshold level for immunosuppression observed in harbor
      seals (209pg/g).

PMID- 19110353
TI  - Evolution of tolerance to PCBs and susceptibility to a bacterial pathogen (Vibrio
      harveyi) in Atlantic killifish (Fundulus heteroclitus) from New Bedford (MA, USA)
      harbor.
AB  - A population of the non-migratory estuarine fish Fundulus heteroclitus (Atlantic
      killifish) resident to New Bedford (NB), Massachusetts, USA, an urban harbor
      highly contaminated with polychlorinated biphenyls (PCBs), demonstrates recently
      evolved tolerance to some aspects of PCB toxicity. PCB toxicology, ecological
      theory, and some precedence supported expectations of increased susceptibility to
      pathogens in NB killifish. However, laboratory bacterial challenges of the marine
      pathogen Vibrio harveyi to wild fish throughout the reproductive season and to
      their mature laboratory-raised progeny demonstrated comparable survival by NB and
      reference killifish, and improved survival by NB males. These results are
      inconsistent with hypothesized trade-offs of adaptation, and suggest that evolved
      tolerance in NB killifish may include mechanisms that minimize the
      immunosuppressive effects of PCBs. Compensatory strategies of populations
      persisting in highly contaminated environments provide a unique perspective for
      understanding the long-term ecological effects of toxic chemicals.

PMID- 19110355
TI  - Total gaseous concentrations in mercury in Seoul, Korea: Local sources compared
      to long-range transport from China and Japan.
AB  - Total gaseous mercury (TGM) and carbon monoxide (CO) were measured every 5min and
      hourly, respectively, in Seoul, Korea, from February 2005 through December 2006.
      The mean concentrations of TGM and CO were 3.44+/-2.13ngm(-3) and 613+/-323ppbv,
      respectively. TGM and CO concentrations were highest during the winter and lowest
      during the summer. In total, 154 high TGM concentration events were identified:
      86 were classified as long-range transport events and 68 were classified as local
      events. The TGM and CO concentrations were well correlated during all long-range
      transport events and were weakly correlated during local events. Five-day
      backward trajectory analysis for long-range transport events showed four
      potential source regions: China (79%), Japan (13%), the Yellow Sea (6%), and
      Russia (2%). Our results suggest that measured DeltaTGM/DeltaCO can be used to
      identify long-range transported mercury and to estimate mercury emissions from
      long-range transport.

PMID- 19110356
TI  - Polybrominated, polychlorinated and monobromo-polychlorinated dibenzo-p
      dioxins/dibenzofurans and dioxin-like polychlorinated biphenyls in marine surface
      sediments from Hong Kong and Korea.
AB  - In this study we investigated occurrences and distribution patterns of dioxin
      related compounds (DRCs) such as polybrominated dibenzo-p-dioxins/dibenzofurans
      (PBDD/Fs), polychlorinated dibenzo-p-dioxins/dibenzofurans (PCDD/Fs), monobromo
      polychlorinated dibenzo-p-dioxins/dibenzofurans (MoBPCDD/Fs) and dioxin-like
      polychlorinated biphenyls (DL-PCBs) in marine surface sediments collected from
      the coastal waters of Hong Kong and Korea. In most sampling sites, concentrations
      of PCDDs were the highest, followed by DL-PCBs, PCDFs, PBDFs, PBDDs, MoBPCDDs and
      MoBPCDFs in this order. Levels of PBDD/Fs were generally 1-2 orders of magnitude
      lower than chlorinated analogues. Levels of PCDDs are higher than PCDFs in Hong
      Kong while levels of PBDFs are higher than PBDDs in Korea (p<0.05). Report of
      PBDD/Fs and MoBPCDD/Fs in sediments from East Asian countries is novel and
      original. Environmental levels of PBDD/Fs are supposed to start increasing in
      accordance with rising production, use and disposal of brominated flame
      retardants (BFRs) and recycling processes of e-waste in Asian developing
      countries.

PMID- 19110357
TI  - The occurrence of illicit and therapeutic pharmaceuticals in wastewater effluent
      and surface waters in Nebraska.
AB  - The occurrence and estimated concentration of twenty illicit and therapeutic
      pharmaceuticals and metabolites in surface waters influenced by wastewater
      treatment plant (WWTP) discharge and in wastewater effluents in Nebraska were
      determined using Polar Organic Chemical Integrative Samplers (POCIS). Samplers
      were installed in rivers upstream and downstream of treated WWTP discharge at
      four sites and in a discharge canal at a fifth location. Based on differences in
      estimated concentrations determined from pharmaceuticals recovered from POCIS,
      WWTP effluent was found to be a significant source of pharmaceutical loading to
      the receiving waters. Effluents from WWTPs with trickling filters or trickling
      filters in parallel with activated sludge resulted in the highest observed in
      stream pharmaceutical concentrations. Azithromycin, caffeine, 1,7
      dimethylzanthine, carbamazepine, cotinine, DEET, diphenhydramine, and
      sulfamethazine were detected at all locations. Methamphetamine, an illicit
      pharmaceutical, was detected at all but one of the sampling locations,
      representing only the second report of methamphetamine detected in WWTP effluent
      and in streams impacted by WWTP effluent.

PMID- 19110358
TI  - Inflammation, hemostasis, and the risk of kidney function decline in the
      Atherosclerosis Risk in Communities (ARIC) Study.
AB  - BACKGROUND: Inflammation and hemostasis may increase the risk of kidney function
      decline; however, data from prospective studies are sparse. STUDY DESIGN: The
      Atherosclerosis Risk in Communities (ARIC) Study, a prospective observational
      cohort. SETTING & PARTICIPANTS: We used data from 14,854 middle-aged adults from
      4 different US communities. PREDICTOR: Markers of inflammation and hemostasis
      were examined. OUTCOMES & MEASUREMENTS: The risk of kidney function decrease
      associated with these markers was studied. Glomerular filtration rate (GFR) was
      calculated from serum creatinine levels using the 4-variable Modification of Diet
      in Renal Disease (MDRD) Study equation. Chronic kidney disease (CKD) was defined
      as: (1) a decrease in estimated GFR to less than 60 mL/min/1.73 m2 from greater
      than 60 mL/min/1.73 m2 at baseline, or (2) a hospitalization discharge or death
      coded for CKD. Serum creatinine was measured at baseline and the 3- and 9-year
      follow-up visits. Hazard ratios (HRs) of CKD associated with increased levels of
      inflammatory and hemostatic variables were estimated by using multivariate Cox
      proportional hazards regression. RESULTS: 1,787 cases of CKD developed between
      1987 and 2004. After adjusting for demographics, smoking, blood pressure,
      diabetes, lipid levels, prior myocardial infarction, antihypertensive use,
      alcohol use, year of marker measurement, and baseline renal function using
      estimated GFR, the risk of incident CKD increased with increasing quartiles of
      white blood cell count (HR quartile 4 versus quartile 1, 1.30; 95% confidence
      interval [CI], 1.12 to 1.50; P trend = 0.001), fibrinogen (HR, 1.25; 95% CI, 1.09
      to 1.44; P < 0.001), von Willebrand factor (HR, 1.46; 95% CI, 1.26 to 1.68; P <
      0.001), and factor VIIIc (HR, 1.39; 95% CI, 1.20 to 1.60; P < 0.001). A strong
      inverse association was found between serum albumin level and risk of CKD (HR,
      0.63; 95% CI, 0.55 to 0.72; P < 0.001). No independent association was found with
      factor VIIc level. LIMITATIONS: Although we lacked a direct measure of kidney
      function, associations were robust to case definitions. CONCLUSIONS: Markers of
      inflammation and hemostasis are associated with greater risk of kidney function
      decrease. Findings suggest that inflammation and hemostasis are antecedent
      pathways for CKD.

PMID- 19110359
TI  - A randomized, double-blind, placebo-controlled study to assess the efficacy and
      safety of cinacalcet HCl in participants with CKD not receiving dialysis.
AB  - BACKGROUND: Secondary hyperparathyroidism is observed in patients with early
      chronic kidney disease (CKD). This study investigated the safety and efficacy of
      cinacalcet for secondary hyperparathyroidism in participants with CKD not
      receiving dialysis. STUDY DESIGN: Double-blind, randomized, 32-week, phase 3
      study. SETTING & PARTICIPANTS: 404 participants with stage 3 or 4 CKD from 73
      centers in 9 countries. INTERVENTIONS: Cinacalcet:placebo (3:1 ratio). OUTCOMES &
      MEASUREMENTS: Proportion of participants with a mean decrease of 30% or greater
      in intact parathyroid hormone (iPTH) level, proportion with iPTH level of 70 or
      less or 110 or less pg/mL (stage 3 and 4 CKD, respectively), and mean percentage
      of iPTH change from baseline, all during the efficacy-assessment phase. RESULTS:
      A greater proportion of cinacalcet than placebo participants achieved a 30% or
      greater decrease in iPTH level (74% versus 28%; P < 0.001), corresponding to a
      43.1% decrease in iPTH level from baseline (cinacalcet) compared with a 1.1%
      increase (placebo). At week 32, serum calcium levels were 8.9 +/- 0.8 mg/dL (
      8.9%; cinacalcet) and 9.9 +/- 0.6 mg/dL (+0.8%; placebo), phosphorus levels were
      4.5 +/- 1.0 mg/dL (+21.4%) and 4.0 +/- 0.7 mg/dL (+6.8%), and calcium-phosphorus
      product values were 40.1 +/- 8.3 mg(2)/dL(2) (+18.9%) and 38.9 +/- 6.9
      mg(2)/dL(2) (+17.1%), respectively. During the study course, 62% (cinacalcet) and
      1% (placebo) of participants experienced 2 consecutive serum calcium
      concentrations less than 8.4 mg/dL. They generally were asymptomatic and without
      significant clinical consequences. Treatment generally was well tolerated, and
      most adverse events were mild to moderate in severity. LIMITATIONS: The study was
      not designed to assess the effects of cinacalcet on vascular calcification, bone
      histomorphometric parameters, or other clinical outcomes. It is not known whether
      the observed differences in changes in iPTH levels are clinically more important
      than observed differences in changes in serum calcium or phosphorus levels or
      dosages of vitamin D sterols and phosphate binders. CONCLUSIONS: These data show
      that cinacalcet treatment in patients with CKD not receiving dialysis can
      decrease plasma iPTH levels, but with frequent (albeit generally asymptomatic)
      serum calcium levels less than 8.4 mg/dL and increases in serum phosphorus
      levels.

PMID- 19110360
TI  - Actor modelling and its contribution to the development of integrative strategies
      for management of pharmaceuticals in drinking water.
AB  - Widespread presence of human pharmaceuticals in water resources across the globe
      is documented. While some, but certainly not enough, research on the occurrence,
      fate and effect of pharmaceuticals in water resources has been carried out, a
      holistic risk management strategy is missing. The transdisciplinary research
      project "start" aimed to develop an integrative strategy by the participation of
      experts representing key actors in the problem field "pharmaceuticals in drinking
      water". In this paper, we describe a novel modelling method, actor modelling with
      the semi-quantitative software DANA (Dynamic Actor Network Analysis), and its
      application in support of identifying an integrative risk management strategy.
      Based on the individual perceptions of different actors, the approach allows the
      identification of optimal strategies. Actors' perceptions were elicited by
      participatory model building and interviews, and were then modelled in perception
      graphs. Actor modelling indicated that an integrative strategy that targets
      environmentally-responsible prescription, therapy, and disposal of
      pharmaceuticals on one hand, and the development of environmentally-friendly
      pharmaceuticals on the other hand, will likely be most effective for reducing the
      occurrence of pharmaceuticals in drinking water (at least in Germany where the
      study was performed). However, unlike most other actors, the pharmaceutical
      industry itself does not perceive that the production of environmentally-friendly
      pharmaceuticals is an action that helps to achieve its goals, but contends that
      continued development of highly active pharmaceutical ingredients will help to
      reduce the occurrence of pharmaceuticals in the water cycle. Investment in
      advanced waste or drinking water treatment is opposed by both the wastewater
      treatment company and the drinking water supplier, and is not mentioned as
      appropriate by the other actors. According to our experience, actor modelling is
      a useful method to suggest effective and realisable integrative risk management
      strategies in complex problem fields that involve many societal actors.

PMID- 19110361
TI  - Older people and their social spaces: a study of well-being and attachment to
      place in Aotearoa New Zealand.
AB  - A sense of belonging or attachment to place is believed to help maintain a sense
      of identity and well-being, and to facilitate successful adjustments in old age.
      Older people in particular have been shown to draw meaning and security from the
      places in which they live. Qualitative data from multiple conversational
      interviews held over the period of a year with each of 83 community-dwelling
      older people in Auckland within the context of a study conducted from 2006 to
      2008 are interpreted to explore how older people relate to their social and
      physical environments, with a specific focus on attachment to place and the
      meaning of home. The concept of 'social space' is proposed, to capture the
      elastic physical, imaginative, emotional and symbolic experiences of and
      connections to people and place across time and in scope. Talking with older
      people themselves gave a rich account of attachment to place, social spaces, and
      well-being. Our participants had strong attachments to their homes and
      neighbourhoods, extensive participation in 'beyond spaces', and shrinking social
      worlds. They did not, however necessarily view changes as negative; instead there
      was a delicate negotiation of positive and negative aspects, and complex
      engagement with 'social space' as a profoundly meaningful construct.

PMID- 19110363
TI  - Evolution of co-management: role of knowledge generation, bridging organizations
      and social learning.
AB  - Over a period of some 20 years, different aspects of co-management (the sharing
      of power and responsibility between the government and local resource users) have
      come to the forefront. The paper focuses on a selection of these: knowledge
      generation, bridging organizations, social learning, and the emergence of
      adaptive co-management. Co-management can be considered a knowledge partnership.
      Different levels of organization, from local to international, have comparative
      advantages in the generation and mobilization of knowledge acquired at different
      scales. Bridging organizations provide a forum for the interaction of these
      different kinds of knowledge, and the coordination of other tasks that enable co
      operation: accessing resources, bringing together different actors, building
      trust, resolving conflict, and networking. Social learning is one of these tasks,
      essential both for the co-operation of partners and an outcome of the co
      operation of partners. It occurs most efficiently through joint problem solving
      and reflection within learning networks. Through successive rounds of learning
      and problem solving, learning networks can incorporate new knowledge to deal with
      problems at increasingly larger scales, with the result that maturing co
      management arrangements become adaptive co-management in time.

PMID- 19110364
TI  - The axial distribution of lesion-site atherosclerotic plaque components: an in
      vivo volumetric intravascular ultrasound radio-frequency analysis of lumen
      stenosis, necrotic core and vessel remodeling.
AB  - Radio-frequency intravascular ultrasound (IVUS) analysis characterizes
      atherosclerotic plaques into necrotic core (NC), dense calcium (DC), fibrofatty
      (FF) and fibrotic (FI) tissue. We studied axial plaque component distribution
      with respect to stenosis and remodeling. Preintervention virtual histology (VH)
      IVUS was performed in 81 pts (90 de novo lesions: 43 left anterior descending
      artery [LAD] and 47 right coronary artery [RCA]). VH-IVUS at the reference,
      minimum lumen area (MLA) and maximum NC (MaxNC) sites were analyzed. Pullback
      length of 31.1 +/- 12.0 mm spanned a lesion length of 13.8 +/- 9.5 mm. The MaxNC
      site was located at the MLA in 3.3% of lesions, proximal to the MLA in 61% of
      lesions (by 4.11 mm) and distal to the MLA in 35.6% of lesions (by 3.56 mm). The
      %DC was greater at the MaxNC and %FI and %FF plaque were less than at the MLA
      site. Lesion fiberoatheromas (FAs) were more often detected at the MaxNC than the
      MLA (96% versus 51%) and were more often classified as thin-caped or multilayered
      than the MLA sites. The remodeling index was larger at the MaxNC than MLA sites
      and correlated with the NC area both at the MLA (r(2) 0.068, p = 0.013) and at
      the MaxNC (r(2) 0.074, p = 0.009). In conclusion, grey-scale and VH-IVUS analysis
      showed that the MLA is rarely at the site of greatest instability (largest NC and
      remodeling) and necrotic core on VH is correlated with remodeling index. These in
      vivo findings are consistent with previously reported histopathologic data and
      have important implications for the detection and treatment of coronary artery
      disease.

PMID- 19110362
TI  - Disruption of the meprin alpha and beta genes in mice alters homeostasis of
      monocytes and natural killer cells.
AB  - Meprin metalloproteases are implicated in inflammatory bowel disease, which
      involves dysfunction of immune cells. However, the roles of meprins in the immune
      and hematological system remain uncharacterized. In this report, we demonstrate
      that meprins were expressed in the hematological system, and meprin alpha/beta
      null (alpha(-/-)/beta(-/-)) mice had decreased prevalence of resident monocytes
      and natural killer (NK) cells in blood, with a concomitant accumulation of
      inflammatory monocytes and NK cells in bone marrow. In contrast, T and B
      lymphocytes were not affected by meprin deficiency. In response to acute
      inflammation induced by intraperitoneal injection of thioglycollate, meprin
      deficient mice exhibited higher body temperature than wild-type mice, which was
      correlated with retention of inflammatory monocytes, but persistent low
      prevalence of NK cells in blood. These results indicate that meprin
      metalloproteases play important roles in the homeostasis of monocytes and NK
      cells, and possibly are involved in egress of these two type cells from bone
      marrow and homing to the periphery. Our findings are the first report to
      demonstrate that metalloproteases affect homeostasis of leukocytes, which have
      important implications for understanding physiology of and pathogenesis in the
      hematological system.

PMID- 19110365
TI  - Myocardial injury induced by ultrasound-targeted microbubble destruction:
      evidence for the contribution of myocardial ischemia.
AB  - Ultrasound-targeted microbubble destruction (UTMD) can cause left ventricular
      (LV) dysfunction and tissue alterations in rats when high ultrasound (US) energy
      and long duration of imaging are used. However, the mechanism underlying these
      alterations remains unclear. The aim of the present work was to investigate the
      possible role of ischemia in the pathogenesis of the UTMD-induced LV damages in
      rats. To address this issue, rat hearts were exposed in situ to perfluorocarbon
      enhanced sonicated dextrose albumin (PESDA) and US at peak negative pressures of
      0.6, 1.2 or 1.8 MPa for 1, 3, 9, 15 or 30 min. Blood pressure and
      electrocardiogram were continuously recorded during insonation. LV function was
      assessed before and immediately after US exposure, as well as at 24 h and 7 d. At
      each time point, groups of rats were euthanized and their hearts were harvested
      for morphologic analysis. Rats exposed to either PESDA alone or US alone showed
      no functional or morphologic abnormalities. By contrast, rats exposed to both
      PESDA and US exhibited transient LV dysfunction, transient ST-segment elevation,
      premature ventricular contractions, microvascular ruptures, contraction band
      necrosis and morphologic tissue damage. These bio-effects were spontaneously and
      completely reversible by one week, except in the groups exposed to the highest
      peak negative pressure for the longest duration, in which mild dysfunction
      persisted and interstitial fibrosis developed. In conclusion, simultaneous
      exposure of rat hearts to PESDA and US in vivo results in significant bio-effects
      that are similar to myocardial ischemia, including transient regional LV
      dysfunction, transient ST-segment elevation and myocyte contraction band
      necrosis.

PMID- 19110366
TI  - Heart valve involvement in Fabry cardiomyopathy.
AB  - Fabry disease is a rare X-linked lysosomal storage disorder leading to an
      accumulation of glycosphingolipids in all tissues and organs including the heart.
      Among the pathologies of myocardial involvement, reviews and registry data list
      affection of heart valves and its hemodynamic significance as predominant
      alterations during progression of the disease. We thought to approach this
      uncertainty with a systematic observational study. In a single center study, 111
      patients with genetically proven Fabry disease were systematically investigated
      by echocardiography for abnormalities of the valves in the left (aortic and
      mitral valve) and right heart (pulmonary and tricuspid valve). In addition, 60
      patients were followed by echocardiography for 2.7 +/- 1.5 y (range 1 to 6). Both
      valve stenosis and regurgitation were classified as mild, moderate or severe.
      Overall, no patient had severe heart valve abnormalities. The most frequent
      findings were mild aortic (n = 17), mitral (n = 57) and tricuspid (n = 38) valve
      regurgitation. Only two patients showed mild aortic valve stenosis. Moderate
      aortic (n = 1), mitral (n = 2) or tricuspid (n = 1) regurgitation were rarely
      detected. All Fabry patients in advanced stages (n = 9) had only mild mitral
      regurgitation and one of them had mild aortic and mitral regurgitation, moderate
      tricuspid regurgitation and mild aortic stenosis. Thirty patients had completely
      normal valve function. There was no significant change toward hemodynamic
      relevant heart valve abnormalities during follow-up. Mild left ventricular valve
      regurgitations are frequent in Fabry disease. However, these valve abnormalities
      are not the major limitations for the Fabry heart.

PMID- 19110367
TI  - Microbubble destruction during intravenous administration: a preliminary study.
AB  - The concentration and size distribution of microbubble suspensions are important
      parameters for both diagnostic and therapeutic applications. The aim of this
      preliminary study was to investigate the relationship between changes in the
      microbubble population and the administration process variables, specifically
      syringe inner diameter, needle inner diameter, volume flow rate and the liquid in
      which the microbubbles are suspended. It was found that reducing either the
      syringe or needle inner diameter produced large reductions in microbubble
      concentration during administration, as much as 99.9% for needle inner diameters
      <0.24 mm. Increasing the volume flow rate up to 3 mL/min and changing the
      suspending fluid from distilled water to glycerol, however, were both found to
      reduce the degree of microbubble destruction. Further work is needed to fully
      explain these observations. However, investigation of the response of
      microbubbles to changes in hydrostatic pressure only, indicated that this was
      unlikely to be the main mechanism of destruction and hence that shear stress was
      a more important factor. Comparison with findings from another recent study of
      microbubble stability indicated that microbubble size, concentration and
      composition were also important parameters and should be taken into account in
      designing administration procedures for microbubble agents. It was concluded that
      current procedures should be reviewed, particularly for therapeutic applications,
      and that the results should also be taken into account when assessing the
      accuracy of microbubble size distribution measurements obtained using automatic
      particle sizing equipment in which microbubbles are made to flow under pressure.

PMID- 19110368
TI  - Temporal and spatial detection of HIFU-induced inertial and hot-vapor cavitation
      with a diagnostic ultrasound system.
AB  - The onset and presence of inertial cavitation and near-boiling temperatures in
      high-intensity focused ultrasound (HIFU) therapy have been identified as
      important indicators of energy deposition for therapy guidance. Passive
      cavitation detection is commonly used to detect bubble emissions, where a fixed
      focus single-element acoustic transducer is typically used as a passive
      cavitation detector (PCD). This technique is suboptimal for clinical
      applications, because most PCD transducers are tightly focused and afford limited
      spatial coverage of the HIFU focal region. A Terason 2000 Ultrasound System was
      used as a PCD array to expand the spatial detection region for cavitation by
      operating in passive mode, obtaining the radiofrequency signals corresponding to
      each scan line and filtering the contribution from scattering of the HIFU signal
      harmonics. This approach allows for spatially resolved detection of both inertial
      and stable cavitation throughout the focal region. Measurements with the PCD
      array during sonication with a 1.1-MHz HIFU source in tissue phantoms were
      compared with single-element PCD and thermocouple sensing. Stable cavitation
      signals at the harmonics and superharmonics increased in a threshold fashion for
      temperatures >90 degrees C, an effect attributed to high vapor pressure in the
      cavities. Incorporation of these detection techniques in a diagnostic ultrasound
      platform could result in a powerful tool for improving HIFU guidance and
      treatment.

PMID- 19110369
TI  - Accuracy and reproducibility of a novel dual-beam vector Doppler method.
AB  - Conventional Doppler ultrasound (US) investigations are limited to detect only
      the axial component of the blood velocity vector. A novel dual-beam method has
      been recently proposed in which the Doppler angle is estimated through a
      reference US beam, and the velocity magnitude through a measuring US beam,
      respectively. In this study, the performance of such a method has been assessed
      quantitatively through in vitro and in vivo measurements made in different
      experimental conditions. In vitro, more than 300 acquisitions were completed
      using seven transducers to insonify a straight tube phantom at different Doppler
      angles. In steady laminar flow conditions, the velocity magnitude was measured
      with mean error of -1.9% (95% confidence interval: -2.33% to -1.47%) and standard
      deviation of 3.4%, with respect to a reference velocity. In pulsatile flow
      conditions, reproducibility tests of the entire velocity waveforms provided an
      average coefficient of variation (CV) of 6.9%. For peak velocity measurements
      made at five Doppler angles and three flow rates, the intrasession and
      intersession CVs were in the range 0.8-3.7% and 2.9-10.6%, respectively. The peak
      systolic velocities (PSVs) in the common carotid arteries of 21 volunteers were
      estimated with 95% limits of agreement of +/- 9.6 cm/s (intersession). This
      analysis shows that the proposed dual-beam method is capable of overcoming the
      Doppler angle ambiguity by producing reliable velocity measurements over a large
      set of experimental conditions.

PMID- 19110370
TI  - Sonoporation by ultrasound-activated microbubble contrast agents: effect of
      acoustic exposure parameters on cell membrane permeability and cell viability.
AB  - This work investigates the effect of ultrasound exposure parameters on the
      sonoporation of KHT-C cells in suspension by perflutren microbubbles. Variations
      in insonating acoustic pressure (0.05 to 3.5 MPa), pulse frequency (0.5 to 5.0
      MHz), pulse repetition frequency (10 to 3000 Hz), pulse duration (4 to 32 micros)
      and insonation time (0.1 to 900 s) were studied. The number of cells
      permeabilised to a fluorescent tracer molecule (70 kDa FITC-dextran) and the
      number of viable cells were measured using flow cytometry. The effect of exposure
      on the microbubble population was measured using a Coulter counter. Cell
      viability and membrane permeability were found to depend strongly on the acoustic
      exposure conditions. Cell permeability increased and viability decreased with
      increasing peak negative pressure, pulse repetition frequency, pulse duration and
      insonation time and with decreasing pulse centre frequency. The highest
      therapeutic ratio (defined as the ratio of permeabilised to nonviable cells)
      achieved was 8.8 with 32 +/- 4% permeabilization and 96 +/- 1% viability at 570
      kPa peak negative pressure, 8 micros pulse duration, 3 kHz pulse repetition
      frequency, 500 kHz centre frequency and 12 s insonation time with microbubbles at
      3.3% volume concentration. These settings correspond to an acoustic energy
      density (E(SPPA)) of 3.12 J/cm(2). Cell permeability and viability did not
      correlate with bubble disruption. The results indicate that ultrasound exposure
      parameters can be optimized for therapeutic sonoporation and that bubble
      disruption is a necessary but insufficient indicator of ultrasound-induced
      permeabilization.

PMID- 19110371
TI  - Safety and effectiveness of extracorporeal shockwave therapy: results of a rabbit
      model of chronic osteomyelitis.
AB  - Extracorporeal shockwave therapy (ESWT) is applied successfully in various
      orthopedic disorders. Since shockwaves have demonstrated significant bactericidal
      effectiveness in vitro, safety and effectiveness of ESWT in vivo were evaluated
      in a rabbit model of osteomyelitis. Chronic osteomyelitis was induced by
      injecting sodium morrhuate and Staphylococcus aureus into the proximal tibia of
      12 New Zealand white rabbits. Four and five wk after the initial operation, soft
      focused ESWT was applied twice to the infected limbs. Clinical parameters and
      laboratory values were followed and blood samples were taken for culture before
      and 30 min after ESWT. Following sacrifice after 8 wk, lungs, spleen and kidneys
      were studied histologically for signs of sepsis and secondary infection. Tibial
      osteomyelitis was assessed clinically, and by radiologic, microbiologic and
      histologic procedures. Signs of bacterial spreading were not detectable after
      ESWT, neither in blood cultures nor in histologic analyses of representative
      organs. Temperature, body weight, C-reactive protein and white blood cell levels
      also remained unchanged after ESWT. Of particular interest, histologic scores of
      osteomyelitis were significantly decreased in the ESWT-group compared to the
      untreated control (p = 0.019). However, S. aureus was still detectable in tissue
      samples of all animals. This is the first study investigating the effects of ESWT
      applied to infected target areas. ESWT of infected bone did neither induce
      bacterial spreading nor worsening of infection, and the results suggest the
      reported treatment protocol of ESWT to be beneficial in the treatment of chronic
      bone infections.

PMID- 19110372
TI  - New image characteristics in endobronchial ultrasonography for differentiating
      peripheral pulmonary lesions.
AB  - Endobronchial ultrasonography (EBUS) rapidly and accurately localizes peripheral
      pulmonary lesions. It can aid differential diagnosis by characterizing lesions
      and discriminating between neoplastic and non-neoplastic disease. From July 2005
      through December 2006, patients with peripheral lesions underwent EBUS
      examination in a tertiary-referral teaching hospital. Image characteristics were
      subsequently correlated with definite histopathologic diagnosis. Three current
      issued image patterns of EBUS were assayed from 40 initial patients, including
      (a) hypoechoic areas, (b) anechoic areas and (c) luminant areas around the probe.
      Excluding 22 cases because of inconsistent typing, 193 patients possessing
      definite diagnoses were enrolled in the investigation, of which 107 cases (55.4%)
      were neoplastic diseases. Hypoechoic areas appeared to be unrelated to the nature
      of the lesions (p = 0.288). Most lesions with anechoic areas were neoplasms (18
      of 21 cases, 85.7%) and lesions without luminant areas suggested non-neoplastic
      disease (19 of 24 cases, 79.2%). Anechoic and luminant areas were significantly
      different between neoplasm and non-neoplasm groups (p = 0.003 and p < 0.001,
      respectively). The average additional time for EBUS required was 3.85 +/- 2.36
      min (range 1 to 13 min). In conclusion, this uncomplicated and time-saving method
      of using EBUS image patterns could provide additional information to facilitate
      differential diagnoses.

PMID- 19110373
TI  - Evidence in support of treating interictal epileptiform discharges in cerebral
      palsy patients without clinical epilepsy for an improved prognostic outcome and
      quality of life.

PMID- 19110375
TI  - Damages of screen-printed carbon nanotube cold cathode during the field emission
      process.
AB  - The field emission properties of the screen-printed carbon nanotube (CNT)
      composite cathode have close relationship with its microstructure. In this study,
      carbon nanotube composite cold cathode with ZnO nano-particles as binding
      material was prepared using screen-printing method. Electric field cycles were
      used to post-treat the carbon nanotube composite cold cathode. During the process
      of electric field cycle treatment, obvious heat-induced damages were observed
      from the cathode. Scanning electron microscope and transmission electron
      microscope were employed to analyze the morphology and microstructure of the
      cathode. The possible mechanisms responsible for damages were discussed.

PMID- 19110374
TI  - Monte Carlo electron-trajectory simulations in bright-field and dark-field STEM:
      implications for tomography of thick biological sections.
AB  - A Monte Carlo electron-trajectory calculation has been implemented to assess the
      optimal detector configuration for scanning transmission electron microscopy
      (STEM) tomography of thick biological sections. By modeling specimens containing
      2 and 3 at% osmium in a carbon matrix, it was found that for 1-microm-thick
      samples the bright-field (BF) and annular dark-field (ADF) signals give similar
      contrast and signal-to-noise ratio provided the ADF inner angle and BF outer
      angle are chosen optimally. Spatial resolution in STEM imaging of thick sections
      is compromised by multiple elastic scattering which results in a spread of
      scattering angles and thus a spread in lateral distances of the electrons leaving
      the bottom surface. However, the simulations reveal that a large fraction of
      these multiply scattered electrons are excluded from the BF detector, which
      results in higher spatial resolution in BF than in high-angle ADF images for
      objects situated towards the bottom of the sample. The calculations imply that
      STEM electron tomography of thick sections should be performed using a BF rather
      than an ADF detector. This advantage was verified by recording simultaneous BF
      and high-angle ADF STEM tomographic tilt series from a stained 600-nm-thick
      section of C. elegans. It was found that loss of spatial resolution occurred
      markedly at the bottom surface of the specimen in the ADF STEM but significantly
      less in the BF STEM tomographic reconstruction. Our results indicate that it
      might be feasible to use BF STEM tomography to determine the 3D structure of
      whole eukaryotic microorganisms prepared by freeze-substitution, embedding, and
      sectioning.

PMID- 19110376
TI  - Effect of amorphous layers on the interpretation of restored exit waves.
AB  - The effects of amorphous layers on the quality of exit wave restorations have
      been investigated. Two independently developed software implementations for exit
      wave restoration have been used to simulated focal series of images of <001>
      SrTiO3 with amorphous carbon layers incorporated. The restored exit waves have
      been compared both qualitatively and quantitatively. We have shown that amorphous
      layers have a strong impact on the quantitative measurements of atomic column
      positions, however, the error in the position measurements is still in the
      picometer range.

PMID- 19110377
TI  - Determination of magnetic vortex polarity from a single Lorentz Fresnel image.
AB  - Nanoscale confinement of the magnetization in a magnetic element often results in
      the creation of a vortex structure. The vortex equilibrium state is characterized
      by the curling of the in-plane magnetization (chirality) and an out-of-plane core
      magnetization. The polarity of the vortex core can point up or down, independent
      of the chirality, and, thus, magnetic elements with a vortex core are interesting
      as four-state logic elements. We present an easy-to-use, quantitative method for
      the determination of both chirality and polarity from a single Fresnel image.
      This method offers direct evidence of the three-dimensional structure of a
      magnetic vortex and has significant advantages over the more complex methods
      currently in use.

PMID- 19110379
TI  - Comparison of two versions of larval development test to detect anthelmintic
      resistance in Haemonchus contortus.
AB  - Larval development (LDT) and micro-agar larval development tests (MALDT) were
      used to compare the reliability and sensitivity of two methods for detecting
      anthelmintic resistance in Haemonchus contortus. The tests were conducted using
      three resistant and four susceptible isolates of H. contortus. Both versions of
      the tests provided comparable results with regard to the characterization of
      benzimidazole and levamisole susceptibility but neither test was sufficiently
      sensitive to discrimination between an ivermectin (IVM) susceptible and an IVM
      resistant isolate. Each test has its own merits with the LDT having the advantage
      of being less time-consuming.

PMID- 19110378
TI  - Nutritional sensitivity of resistance to Trichostrongylus colubriformis in
      lactating ewes.
AB  - It has been suggested that the periparturient breakdown of immunity to parasites
      has a nutritional basis. Our overall hypothesis is that it results from a
      prioritized scarce metabolizable protein (MP) allocation to reproductive
      functions (e.g. milk production) rather than to immune functions. We have earlier
      shown that the relationship between MP supply, milk production and resistance to
      the abomasal nematode Teladorsagia circumcincta provides support for this
      hypothesis. Because nutritional sensitivity of resistance to parasites may differ
      between parasite species, we used the same nutritional protocol to test the
      overall hypothesis with a different parasite. Thus, five levels of dietary MP,
      ranging from 0.60 to 1.2 times assumed requirements, were offered for 4 weeks
      post-parturition to twin-rearing Greyface ewes, experimentally infected with the
      small intestinal nematode Trichostrongylus colubriformis. We hypothesized that
      the initial increments of MP supply would increase milk production without
      affecting the degree of breakdown of immunity whilst later increments would
      reduce the degree of breakdown of immunity. Indeed, the data suggest that the
      first two increments of MP supply increased milk production, whilst final worm
      burdens were reduced from the second increment onwards. MP supply did not affect
      mucosal mast cell concentration but increased globule leukocyte concentration.
      These results support the overall hypothesis that scarce MP allocation is
      prioritized to milk production over immune functions. In addition, the contrast
      between effects of MP supply on resistance to T. colubriformis and to T.
      circumcincta supports the view that periparturient immunity to small intestinal
      nematodes may be less sensitive to nutrient scarcity than periparturient immunity
      to abomasal nematodes.

PMID- 19110380
TI  - Unusual contact burn due to analgesic thermal patch: A case report.

PMID- 19110381
TI  - Trauma-related risk factors for substance abuse among male versus female young
      adults.
AB  - Clinical efforts to reduce risk for Substance Use Disorders (SUDs) among young
      adults rely on the empirical identification of risk factors for addictive
      behaviors in this population. Exposure to traumatic events and Posttraumatic
      Stress Disorder (PTSD) have been linked with SUDs in various populations.
      Emerging data, particularly from adolescent samples, suggest that traumatic event
      exposure increases risk for SUDs for young women, but not young men. The purpose
      of the current study was to examine trauma-related risk factors for alcohol and
      drug abuse among a national sample of young adults and compare such risk factors
      between men and women. Participants were 1753 young adults who participated in
      the 7-8 year follow-up telephone-based survey to the original National Survey of
      Adolescents. In the full sample, 29.1% met criteria for substance abuse. Trauma
      related risk factors for alcohol and drug abuse differed for men and women.
      Clinical implications of these results are discussed.

PMID- 19110382
TI  - Are some categories of scientific publication more equal than others? On the
      ambiguous use of the label "original work".
AB  - The problem addressed here is the observation that numerous people in academia
      attach differential value to publication category or format rather than
      publication contents alone. This can be formally visible in academic tenure
      procedures where the record of research regularly favours an imbalance of loosely
      called "original work" versus "other". Such practice is a recipe for the
      devaluation of some of the best and fine thinking and work included in "other"
      publications such as reviews, perspective papers, hypotheses, editorials and
      correspondence. In this vein, issue is taken with the label "original" being
      attached to "new results" from an "individual study" alone rather than being a
      criterion of or expectation in any, or at least many, publications beyond
      individual studies or experiments.

PMID- 19110383
TI  - Performance of API Staph ID 32 and Staph-Zym for identification of coagulase
      negative staphylococci isolated from bovine milk samples.
AB  - In this study, the accuracy of two phenotypic tests, API Staph ID 32 and Staph
      Zym, was determined for identification of coagulase-negative staphylococci (CNS)
      from bovine milk samples in comparison with identification based on DNA
      sequencing. A total of 172 CNS isolated from bovine milk were classified into 17
      species. The most frequently isolated species based on rpoB sequencing were
      Staphylococcus chromogenes and Staphylococcus epidermidis, followed by
      Staphylococcus xylosus, Staphylococcus warneri and Staphylococcus equorum (37,
      13, 9, 8 and 6% of isolates, respectively). The API Staph ID 32 correctly
      identified 41% of the CNS isolates. Best agreement with rpoB sequence based
      species identification was found for S. epidermidis, Staphylococcus hyicus and S.
      xylosus (100, 89 and 87%, respectively). The positive predictive value was 89,
      100 and 52%, respectively. Poor sensitivity was observed for 3 of the 5 most
      frequently found species, S. chromogenes (37%), Staphylococcus warneri (15%) and
      S. equorum (0%) albeit with specificity of 100%. The Staph-Zym needed additional
      tests for 66% of the isolates and identified 31% of the CNS isolates correctly.
      Good sensitivity was found for S. epidermidis, S. simulans and S. xyloxus (100,
      78 and 73%, respectively). The positive predictive value was 89, 78 and 98%,
      respectively. Poor sensitivity was observed for S. chromogenes, S. warneri and S.
      equorum (0, 54 and 0%, respectively) but with a specificity of 100, 99 and 100%,
      respectively. Both phenotypic tests misidentified a large proportion of CNS
      isolates and were thus unsuitable for identification of CNS species from bovine
      milk samples.

PMID- 19110384
TI  - Prevalence of hematological abnormalities and detection of infected bone marrow
      cells in asymptomatic cats with feline immunodeficiency virus infection.
AB  - Peripheral blood cytopenia such as anemia, leukopenia with neutropenia and
      thrombocytopenia is frequently observed in cats infected with feline
      immunodeficiency virus (FIV). Although previous studies report that cytopenia has
      been observed in FIV-infected symptomatic cats, yet the asymptomatic cats also
      present cytopenia occasionally. In the present study, hematological and
      virological analyses in FIV-infected asymptomatic cats were carried out to
      understand the prevalence and pathogenesis of peripheral blood cytopenia in FIV
      infection. Hematological abnormalities were detected in 24 of 50 FIV-infected
      asymptomatic cats (48%) in which no other cause of cytopenia than FIV infection
      was observed. Anemia only, neutropenia only, thrombocytopenia only, bicytopenia
      and pancytopenia were observed in 10%, 10%, 6%, 14% and 8%, respectively. Bone
      marrow (BM) examination was performed in 8 FIV-infected asymptomatic cats with
      peripheral blood cytopenia. Myeloid dysplasia was observed in 4 cats with
      neutropenia of which 2 cats with concurrent thrombocytopenia presented
      morphological abnormalities of megakaryocytes. FIV-infected BM cells in the 8
      cats were analyzed by PCR and immunocytochemistry. Lobulated mononuclear cells in
      BM were infected with FIV in 5 cats with neutropenia of which 2 cats with
      concurrent thrombocytopenia showed FIV-infected megakaryocytes. Parts of isolated
      stromal cells from BM were infected with FIV in all the 8 cats. Present results
      suggest that FIV infection of BM cells can cause peripheral blood cytopenia and
      myelodysplasia even if the cat is asymptomatic. Such FIV-related hematological
      abnormalities are supposed to be diagnosed as FIV-myelopathy.

PMID- 19110385
TI  - Galactocele and prolactinoma--a pathogenic association?
AB  - A galactocele is a rare form of cystic, benign lesion of the breast, appearing
      when a mammary duct becomes obstructed and over filled with milk. It is usually
      found in postpartum women, either lactating or not. There are only a few cases
      reported that are not immediately linked to the lactation, as seen in
      postmenopausal women or in men. Furthermore, the relationship to overproduction
      of prolactine, a growth factor for the breast epithelium is not very well defined
      at this moment. We present such an unusual case of a 37-year-old female patient
      who has no history of birth or abortion. She was diagnosed with both
      microprolactinoma and galactocele whose dimensions seemed to be related to the
      evolution of the pituitary tumor and serum prolactine. Because no other etiology
      could be found in the young patient for the mammary galactocele, the prolactine
      excess is the most probable cause. Even considering the rarity of the association
      it is important to point the hormonal role in changing the anatomy of the breast.

PMID- 19110386
TI  - Parity and postmenopausal osteoporosis.

PMID- 19110388
TI  - [Mondor's disease, report on three cases and literature review].
AB  - Mondor's disease is spontaneously remitting benign superficial thrombophlebitis
      involving healthy veins. Fewer than 400 cases have been reported in the world
      literature. Typically, subcutaneous angiitis is observed on the upper
      anterolateral aspect of the chest wall. We report three cases in which Mondor's
      disease occurred after surgery for breast cancer in one patient, and had no
      apparent cause in two other patients. The relationship with breast cancer and
      risk factors suggests that routine mammography is advisable. For patients
      presenting idiopathic Mondor's disease, follow-up is of utmost importance.

PMID- 19110387
TI  - Sudden unexpected death in a female fitness athlete, with a possible connection
      to the use of anabolic androgenic steroids (AAS) and ephedrine.
AB  - The use of anabolic androgenic steroids (AAS) has been associated with different
      adverse effects, some of which potentially lethal. Most users of AAS are male,
      but the prevalence of such use appears to be increasing in females. Here we
      present a sudden unexpected death in a female fitness athlete with a possible
      connection to use of doping agents.

PMID- 19110389
TI  - [Variable platelet response to aspirin and new therapeutic targets].
AB  - Aspirin is the first-line oral antiplatelet drug to prevent thromboembolic
      arterial occlusions. Aspirin irreversibly inhibits cyclooxygenase (COX) 1
      involved in the platelet production of thromboxane (TX) A(2), an inducer of
      vasoconstriction and a platelet activating agent. Recurrent vascular events
      despite aspirin intake, combined with laboratory evidence of poor antiplatelet
      effect, suggested what has been called "aspirin resistance". For clarity's sake a
      real aspirin resistance would be the absence of COX1 inhibition due to intrinsic
      platelet factors (which has never been reported). What has been described is
      (expected) variability. COX1 inhibition can be insufficient to modify TX
      dependent platelet behaviour. Other agonists, the production of which does not
      involve COX1, can stimulate TX-receptors. The antiplatelet effect of aspirin can
      be insufficient for pharmacokinetic or pharmacodynamic reasons, the latter being
      further classified as TX-dependent or not. If platelets are so reactive that
      responses are more TX-independent than normally, then neither aspirin nor any
      drugs acting on this pathway can do the job. These mechanisms should be better
      understood and diagnosed, and this is the prerequisite for the development of
      newer antiplatelet agents.

PMID- 19110390
TI  - [Mortality rates in pediatric septic shock secondary to community-acquired
      infection: about 70 cases].
AB  - GOAL: This study had for aim to determine the mortality rate and the factors
      affecting mortality among 70 children admitted for septic shock secondary to a
      community acquired infection. PATIENTS AND METHODS: A retrospective analysis was
      made of patients admitted between January 1998 and August 2005, in a pediatric
      ICU for septic shock secondary to a community-acquired infection. Neonates under
      7 days of age were excluded from the study. RESULTS: Seventy cases were included
      and 32 (45.7 %) of them died. Their average age was 3.8+/-4.2 years and their
      PRISM during the first 24 hours was 19.2+/-8.4. Sixty-nine children (98.6 %)
      presented with multivisceral failure and 60 (85.7 %) with more than two deficient
      organs. The average time between the observation of first hemodynamic disorders
      and admission to ICU was 9.4+/-11.3 hours. Three independent mortality risk
      factors were identified: failure of more than two organs on admission (OR, 4.4;
      95 % CI [2.1-9.4]), an infusion volume superior to 20ml/kg on the second day of
      resuscitation (OR, 3.4; 95 CI % [1.1-10.3]), and the use of more than two
      vasoactive drugs (OR, 3.3; 95 CI % [1.2-9]).

PMID- 19110391
TI  - Occipital lobe's cortical thinning in ametropic amblyopia.
AB  - BACKGROUND AND PURPOSE: The present study was designed to detect the
      abnormalities of the cortical thickness in children with ametropic amblyopia by a
      computer-aided MRI technique. METHODS: Nine children with ametropic amblyopia and
      eight age-matched normal controls underwent MRI brain scanning that was performed
      on a Siemens Avanto 1.5-T scanner, and standard T(1)-weighted high-resolution
      anatomic scans of magnetization-prepared rapid gradient echo (MPRAGE) sequence
      were obtained. For the cortical thickness analysis, 3D MPRAGE images were
      processed with FreeSurfer software package
      (http://www.nmr.mgh.harvard.edu/freesurfer/), and the cortical thicknesses were
      compared between the patient group and the normal control group. RESULTS: The
      cortical thicknesses of the lingual and pericalcarine areas in the left
      hemisphere and of the cuneus, lateraloccipital and lingual areas in the right
      hemisphere in the amblyopic group were significantly thinner than those of the
      control group (P<.05). CONCLUSION: The changes in cortical thickness of several
      occipital regions in amblyopic patients may be important in the diagnosis and
      treatment of this disease.

PMID- 19110392
TI  - Parallel imaging with 3D TPI trajectory: SNR and acceleration benefits.
AB  - Three-dimensional (3D) twisted projection imaging (TPI) trajectory has a unique
      advantage in sodium ((23)Na) imaging on clinical MRI scanners at 1.5 or 3 T,
      generating a high signal-to-noise ratio (SNR) with a short acquisition time
      (approximately 10 min). Parallel imaging with an array of coil elements transits
      SNR benefits from small coil elements to acquisition efficiency by sampling
      partial k-space. This study investigates the feasibility of parallel sodium
      imaging with emphases on SNR and acceleration benefits provided by the 3D TPI
      trajectory. Computer simulations were used to find available acceleration factors
      and noise amplification. Human head studies were performed on clinical 1.5/3-T
      scanners with four-element coil arrays to verify simulation outcomes. In in vivo
      studies, proton ((1)H) data, however, were acquired for concept-proof purpose.
      The sensitivity encoding (SENSE) method with the conjugate gradient algorithm was
      used to reconstruct images from accelerated TPI-SENSE data sets. Self-calibration
      was employed to estimate coil sensitivities. Noise amplification in TPI-SENSE was
      evaluated using multiple noise trials. It was found that the acceleration factor
      was as high as 5.53 (corresponding to acceleration number 2 x 3, ring-by
      rotation), with a small image error of 6.9% when TPI projections were reduced in
      both polar (ring) and azimuthal (rotation) directions. The average noise
      amplification was as low as 98.7%, or 27% lower than Cartesian SENSE at that
      acceleration factor. The 3D nature of both TPI trajectory and coil sensitivities
      might be responsible for the high acceleration and low noise amplification.
      Consequently, TPI-SENSE may have potential advantages for parallel sodium
      imaging.

PMID- 19110393
TI  - Quantification of slow flow using FAIR.
AB  - Phase contrast (PC)-based MRI methods are considered to be the most accurate
      approach for spatially resolved flow quantification, but the measurement of very
      slow velocities requires signal detection at long echo times and the application
      of strong field gradients. On the other hand, measurements based on time-of
      flight or inflow effects can be conducted at short echo times and without flow
      encoding gradients. A method for imaging flow at velocities of the order of 0.1
      mm/s is presented and validated here. It consists of measuring the apparent spin
      lattice relation rate (R(1)*) of the flowing fluid using magnetization
      preparation by alternating slice-selective and nonselective inversion pulses
      (FAIR or flow-sensitive alternating inversion recovery) and a fast gradient-echo
      detection sequence. This method is appropriate for the quantitative imaging of
      slow flow at low Reynolds numbers in fluids where the T(2) values are too short
      to allow sensitive flow measurements by phase contrast-based methods.

PMID- 19110394
TI  - Preoperative localization of the sensorimotor area using independent component
      analysis of resting-state fMRI.
AB  - Analysis of resting-state functional magnetic resonance imaging (fMRI) data is
      based on detecting low-frequency signal fluctuations in functionally connected
      brain areas. These synchronous fluctuations in resting-state networks have been
      observed in several studies with healthy subjects. In this study, we explored if
      independent component analysis (ICA) can be used to localize the sensorimotor
      area from resting-state fMRI data in patients with brain tumors. Finger-tapping
      activation task and resting-state blood-oxygenation-level-dependent fMRI data
      were acquired from 8 patients with brain tumors and 10 healthy volunteers.
      Sensorimotor task independent components (IC(task)) were used to verify resting
      state independent components (IC(rest)) individually. In addition, sensorimotor
      IC(rest)s were compared between the groups and no significant differences were
      detected in volume, spatial correlation or temporal correlation. These results
      show that it is possible to localize a sensorimotor area from resting-state data
      using ICA in patients with brain tumors. This offers a complementary method for
      assessing the sensorimotor area in subjects with brain tumors who have
      difficulties in performing motor paradigms.

PMID- 19110395
TI  - Teachable moments for health behavior change: a concept analysis.
AB  - OBJECTIVE: "Teachable moments" have been proposed as events or circumstances
      which can lead individuals to positive behavior change. However, the essential
      elements of teachable moments have not been elucidated. Therefore, we undertook a
      comprehensive review of the literature to uncover common definitions and key
      elements of this phenomenon. METHODS: Using databases spanning social science and
      medical disciplines, all records containing the search term "teachable moment*"
      were collected. Identified literature was then systematically reviewed and
      patterns were derived. RESULTS: Across disciplines, 'teachable moment' has been
      poorly developed both conceptually and operationally. Usage of the term falls
      into three categories: (1) "teachable moment" is synonymous with "opportunity"
      (81%); (2) a context that leads to a higher than expected behavior change is
      retrospectively labeled a 'teachable moment' (17%); (3) a phenomenon that
      involves a cueing event that prompts specific cognitive and emotional responses
      (2%). CONCLUSION: The findings suggest that the teachable moment is not
      necessarily unpredictable or simply a convergence of situational factors that
      prompt behavior change but suggest the possible creation of a teachable moment
      through clinician-patient interaction. PRACTICE IMPLICATIONS: Clinician-patient
      interaction may be central to the creation of teachable moments for health
      behavior change.

PMID- 19110396
TI  - Nurse responsiveness to cancer patient expressions of emotion.
AB  - OBJECTIVE: This theoretically based study examined nurse responses to cancer
      patient expressions of emotion using a videotaped, simulated cancer patient.
      METHODS: This study used an experimental crossover design with a videotaped
      patient expressing anger, sadness, and neutral emotion to elicit nurse responses.
      Seventy-four nurses from eight sites participated. Responses were coded using
      Roter interaction analysis system. Correlations explored relationships between
      variables that impact communication (age, gender, work experience, trait anxiety,
      work stress, self-efficacy). Regression models explored the effect of variables
      on nurse affective responsiveness. RESULTS: Patient expressions of sadness
      elicited more affective responses than anger. Expressions of anger or neutral
      emotion elicited more instrumental behaviors than sadness. Variables such as age,
      work stress and work experience were significantly correlated. No variables
      predicted affective responsiveness to patient expressions of anger or sadness.
      CONCLUSION: Nurse communication showed significant variation in response to
      patient emotional expressions. Understanding the relationships between
      demographic, personality, and work variables, and identification of new variables
      that influence nurse-patient communication, has implications for interventional
      studies. PRACTICE IMPLICATIONS: Over 90% of the participants indicated that the
      videotape simulation would be a useful method for teaching and practicing
      communication skills with patients expressing emotions.

PMID- 19110397
TI  - Long-term experience in autologous in vitro endothelialization of infrainguinal
      ePTFE grafts.
AB  - OBJECTIVE: Based on a previous randomized study showing significantly superior
      patency rates for in vitro endothelialized expanded polytetrafluoroethylene
      (ePTFE) grafts we investigated whether it was feasible for a nontertiary
      institution to offer autologous in vitro endothelialization to all elective
      infrainguinal bypass patients who had no suitable saphenous vein available.
      METHODS: Over a period of 15 years, 310 out of 318 consecutive nonacute patients
      (age 64.7 +/- 8.6) received 341 endothelialized ePTFE grafts (308
      femoropopliteal: 153 above knee [AK] and 155 below knee [BK] and 33
      femorodistal). Autologous endothelial cells were harvested from short segments
      (3.9 +/- 1.1 cm) of subcutaneous veins (80% cephalic, 11% basilic, 2% external
      jugular, and 7% saphenous) and grown to mass cultures within 18.9 +/- 4.5 days
      before being confluently lined onto fibrin glue-coated ePTFE grafts. The graft
      diameter was 6 mm (64%) or 7 mm (36%). The overall procedure-related delay for
      graft implantation was 27.6 + 7.8 days. Growth failure prevented 2.5% of patients
      from receiving an endothelialized graft. The mean observation period was 9.6
      years. Primary patencies were obtained from Kaplan-Meier survivorship functions.
      Explants for morphological analysis were obtained from eight patients. RESULTS:
      The overall primary patency rate of femoropopliteal grafts was 69% at 5 years
      (68% [AK] vs 71% [BK]) and 61% at 10 years (59% [AK] vs 64% [BK]). Primary
      patency of 7 mm vs 6 mm grafts was 78%/62% at 5 years and 71%/55% at 10 years.
      The difference between the two groups was statistically significant (log rank
      test P = .023; Breslow test P = .017). Stage I vs II/III patients showed 5-year
      patencies of 67% vs 73% (N.S.) and 10-year patencies of 61%% vs 53% (N.S.). The
      primary patency of femorodistal grafts was 52% at 5 years and 36% at 10 years.
      The limb salvage rate was 94% (fempop) vs 86% (femdistal) at 5 years and 89% vs
      71% at 10 years. All retrieved samples showed the presence of an endothelium
      after 38.9 +/- 17.8 months. CONCLUSION: Autologous in vitro endothelialization
      was shown to be a feasible routine procedure at a nontertiary hospital. Explants
      confirmed the presence of an endothelium years after implantation while the
      primary patency in the particularly challenging subgroup of patients without a
      suitable saphenous vein resembles that of vein grafts.

PMID- 19110398
TI  - Preoperative imatinib mesylate for unresectable or locally advanced primary
      gastrointestinal stromal tumors (GIST).
AB  - AIM: To explore the effect of preoperative imatinib mesylate (IM) in patients
      with unresectable or locally advanced primary gastrointestinal stromal tumor
      (GIST). METHODS: From January 2003 to January 2008, all patients affected by
      bulky localized GIST who presented at our institution were considered for
      preoperative IM with cytoreductive intent. Clinical, pathological and molecular
      characteristics were assessed and the rate of response recorded. Progression-free
      survival (PFS) was calculated according to Kaplan-Meier analysis. RESULTS:
      Fifteen patients (1 esophageal, 7 gastric, 3 duodenal, 4 rectal GISTs) received
      preoperative IM for a median of 9 months. All patients had tumor shrinkage, with
      a median size reduction of 34%. One patient had radiological complete response.
      In all cases an improvement of the originally planned surgical procedure was
      obtained: 3 patients initially considered unresectable underwent complete
      surgery; 7 patients with initial indication for extensive surgery were more
      conservatively operated on; 4 patients initially deemed at high perioperative
      risk underwent safe surgery. Due to the small sample size, no association between
      tumor shrinkage and tumor site, size, IM duration, mutational status and
      pathological response could be formally explored. PFS at 3 years from IM onset
      was 77%. CONCLUSIONS: In unresectable or locally advanced GISTs, preoperative IM
      is a useful tool both to improve resectability and reduce surgical morbidity. It
      should be therefore always be considered before embarking on a major surgical
      procedure. The long-term impact of IM on PFS and survival is presently under
      investigation in multicenter prospective randomized trials.

PMID- 19110399
TI  - Relations between perfectionism and obsessive-compulsive symptoms: examination of
      specificity among the dimensions.
AB  - There is longstanding interest in a purported relation between perfectionism and
      Obsessive-Compulsive Disorder (OCD), but many previous studies have either
      inconsistently measured one of the constructs or not accounted for shared
      distress variance. These two studies investigated whether different measures of
      perfectionism showed unique correlations with obsessive-compulsive symptoms after
      accounting for depression and the cognitive domain of responsibility/threat
      estimation, which both are related strongly to OCD. Contrary to previous
      research, results were that both measures of perfectionism evidenced significant
      unique correlations with OCD beyond variance contributed by the other predictors.
      Further, the strength of association was substantially greater than the
      (statistically significant) perfectionism-depression partial correlation.
      Conversely, content conceptualized as "adaptive" perfectionism showed no
      correlation with any obsessive-compulsive symptoms, but had a significant
      negative correlation with depression. Possible reasons for both convergence and
      discrepancy with previous research are discussed.

PMID- 19110400
TI  - The role of RAGE in aminoguanidine-induced suppression of venous intimal
      hyperplasia in diabetic rats.
AB  - Intimal hyperplasia is one of the major pathological processes in vein graft
      failure with diabetes mellitus. In this study, we tested the hypothesis that the
      suppressive effect of aminoguanidine on intimal hyperplasia is mediated by
      downregulated expression of advanced glycation end products (AGE) and its
      receptor (RAGE) in streptozotocin-induced diabetes. To induce intimal
      hyperplasia, autologous external jugular vein was grafted into the infrarenal
      abdominal aorta in 52 male Sprague-Dawley rats. In diabetic rats, distilled water
      with or without aminoguanidine was administrated, whereas nondiabetic rats were
      given distilled water alone. Vein grafts were harvested at 1 and 4 weeks after
      surgery for morphological analysis and semiquantitative reverse transcriptase
      polymerase chain reaction analysis for RAGE and nuclear factor kappaB (NF-kappaB)
      p65. Serum AGE level was determined by fluorospectrophotometry. Compared to
      nondiabetic rats, serum levels of AGE in diabetic rats administrated distilled
      water were significantly increased. The expression of RAGE and NF-kappaB p65, the
      ratio of intima to media area, and the percentage of proliferating cell nuclear
      antigen (PCNA)-positive cells were significantly increased in the vein graft. In
      diabetic rats treated with aminoguanidine, serum AGE level NF-kappaB p65
      expression, the ratio of intima to media area, and the percentage of PCNA
      positive cells in the vein graft were all significantly decreased. However, no
      difference in the expression of RAGE was found compared to the diabetic group
      given distilled water. Our data suggest that AGE-RAGE may play a key role in
      venous intimal hyperplasia in diabetes mellitus and aminoguanidine suppressed
      intimal hyperplasia by inhibiting this pathway.

PMID- 19110402
TI  - A survey-based index was validated for measuring disease activity in inflammatory
      bowel disease. An evaluation study.
AB  - OBJECTIVE: Crohn's disease is a highly distressful chronic disorder,
      characterized by frequent relapses. A symptom-based disease activity index was
      developed for use in epidemiological research. STUDY DESIGN AND SETTING: One
      hundred and six consecutive patients presenting to a tertiary referral hospital
      in Southern Germany in 2004-2005 participated in a questionnaire-based survey. As
      a reference standard, disease activity was assessed using a clinical index
      (Crohn's Disease Activity Index [CDAI], based on symptoms reported to physician,
      laboratory markers, and physician assessed signs). A linear regression equation
      was calculated based on the survey data on severity of symptoms (dependent
      variable: CDAI). Survey index scores (S-CDAI) were then calculated using the
      estimated coefficients for pain, stools, and general well-being in an independent
      data set. RESULTS: S-CDAI and CDAI showed moderate agreement (kappa=0.57 for
      relapse vs. remission). High activity (high S-CDAI) correlated negatively with
      high quality of life (disease specific: Short Inflammatory Bowel Disease Quality
      of-Life Questionnaire; r=-0.67; generic: Short Form 36 physical summary score, r=
      0.47). Test-retest reliability and sensitivity for change were good (intraclass
      correlation coefficient 0.81). CONCLUSION: A useful, valid, and reliable disease
      activity score was developed, which will facilitate meaningful survey research in
      this chronic disorder.

PMID- 19110401
TI  - Management of a ruptured infected abdominal aortic aneurysm and a
      spondylodiscitis due to Gemella haemolysans.
AB  - Infected aneurysm of the abdominal aorta is an uncommon and highly lethal
      disease, with a >80% rate of death. It is uncommonly associated with
      spondylodiscitis. Management of this rare association of pathology remains
      controversial. This report details the case of a patient with a large vascular
      past history, presenting a scarce association of disease: a ruptured infected
      aneurysm of the abdominal aorta with a spondylodiscitis due to Gemella
      haemolysans. The patient recovered quickly and durably, thanks to an unusual
      cooperation of both vascular surgeons and orthopedists: He underwent an in situ
      graft replacement and a front vertebral fixation in a single-step surgery. Good
      immediate and midterm outcome shows a new way of treatment in this rare but
      severe situation.

PMID- 19110403
TI  - Effects of mood stabilizers on brain reward processes in rats: studies using the
      intracranial self-stimulation paradigm.
AB  - Bipolar disorder is characterized by dysregulated motivation and increased
      hedonistic drive. d-Amphetamine induces manic symptoms in humans and exacerbates
      mania in bipolar disorder patients, effects that are counteracted by mood
      stabilizers. We utilized intracranial self-stimulation (ICSS) to examine how
      lithium (LiCl), valproate (VPA) or their combination that is commonly used in the
      clinic affect brain reward function in rats, and how these drugs affect d
      amphetamine's reward-facilitating effects. Acute intraperitoneal (i.p.)
      administration of LiCl (100, 200 mg/kg), VPA (400 mg/kg) or combined
      administration of subthreshold doses of LiCl (50 mg/kg) and VPA (200 mg/kg)
      increased ICSS thresholds. LiCl (100 mg/kg) and combined administration of LiCl
      and VPA (50 and 200 mg/kg), but not VPA alone (200, 400 mg/kg), attenuated d
      amphetamine's reward-facilitating effects. These results suggest that ICSS
      combined with d-amphetamine constitutes a useful model to explore the elation and
      increased hedonistic drive observed in bipolar patients and ultimately help to
      identify novel pharmacotherapies for bipolar disorder.

PMID- 19110404
TI  - High-resolution solid-state NMR spectroscopy of protons with homonuclear dipolar
      decoupling schemes under magic-angle spinning.
AB  - High-resolution NMR spectroscopy of (1)H spins in the solid state is normally
      rendered difficult due to the strong homonuclear (1)H-(1)H dipolar couplings.
      Even under very high-speed magic-angle spinning (MAS) at ca. 60-70kHz, these
      couplings are not completely removed. An appropriate radiofrequency pulse scheme
      is required to average out the homonuclear dipolar interactions in combination
      with MAS to get high-resolution (1)H NMR spectrum in solid state. Several schemes
      have been introduced in the recent past with a variety of applications also
      envisaged. Development of some of these schemes has been made possible with a
      clear understanding of the underlying spin physics based on bimodal Floquet
      theory. The utility of these high-resolution pulse schemes in combination with
      MAS has been demonstrated for spinning speeds of 10-65kHz in a range of (1)H
      Larmor frequencies from 300 to 800MHz.

PMID- 19110405
TI  - Physical characteristics of rumen contents in two small ruminants of different
      feeding type, the mouflon (Ovis ammon musimon) and the roe deer (Capreolus
      capreolus).
AB  - In domestic ruminants, the stratification of forestomach contents - the results
      of flotation and sedimentation processes - is an important prerequisite for the
      selective particle retention in this organ. A series of anatomical and
      physiological measurements suggests that the degree of this stratification varies
      between browsing and grazing wild ruminants. We investigated the forestomach
      contents of free-ranging mouflon and roe deer shot during regular hunting
      procedures. There was no difference between the species in the degree by which
      forestomach ingesta separated according to size due to buoyancy characteristics
      in vitro. However, forestomach fluid of roe deer was more viscous than that of
      mouflon, and no difference in moisture content was evident between the dorsal and
      the ventral rumen in roe deer, in contrast to mouflon. Hence, the forestomach
      milieu in roe deer appears less favourable for gas or particle separation due to
      buoyancy characteristics. These findings are in accord with notable differences
      in forestomach papillation between the two species. In roe deer, particle
      separation is most likely restricted to the reticulum, whereas in mouflon, the
      whole rumen may pre-sort particles to a higher degree. The results suggest that
      differences in forestomach physiology may occur across ruminant species.

PMID- 19110406
TI  - Determination and pharmacokinetic study of taxifolin in rabbit plasma by high
      performance liquid chromatography.
AB  - Taxifolin has been widely used in the treatment of cerebral infarction and
      sequelae, cerebral thrombus, coronary heart disease and angina pectoris. A
      reliable sensitive reversed-phase high-performance liquid chromatography (RP
      HPLC) method with UV detection for the pharmacokinetic study of taxifolin in
      rabbit plasma after enzymatic hydrolysis was developed and validated for the
      first time. Taxifolin, with biochanin A as the internal standard, was extracted
      from plasma samples by liquid/liquid extraction after hydrolysis with beta
      glucuronidase and sulfatase. Chromatographic separation was conducted on a Luna
      C18 column (4.6 mm x 150 mm, 5 microm particle size) and pre-column (2.0 mm, the
      same sorbent). Two-step linear gradient elution with acetonitrile and 0.03% water
      solution of trifluoroacetic acid as mobile phase at a flow rate of 1.0 ml/min was
      used. The UV detector is set at 290 nm. The elution time for taxifolin and
      biochanin A was approximately 7.9 and 18.3 min, respectively. The calibration
      curve of taxifolin was linear (r > 0.9997) over the range of 0.03-5.0 microg/ml
      in rabbit plasma. The limit of detection (LOD) and limit of quantification (LOQ)
      for taxifolin were 0.03 and 0.11 microg/ml, respectively. The present method was
      successfully applied for the estimation of the pharmacokinetic parameters of
      taxifolin following intravenous and oral administration of lipid solution to
      rabbits. The absolute bioavailability of taxifolin after oral administration of
      lipid solution was 36%.

PMID- 19110407
TI  - Antisickling properties of divanilloylquinic acids isolated from Fagara
      zanthoxyloides Lam. (Rutaceae).
AB  - Fagara zanthoxyloides Lam. (syn. Zanthoxylum zanthoxyloides) (Rutaceae) is the
      most cited Fagara species for the treatment and the prevention of sickle cell
      disease crisis. Sickle cell anemia (SCA) is a public health problem in many
      countries particularly in Africa. The present study was designed to evaluate the
      antisickling properties of three isomeric divanilloylquinic acids (3,4-O
      divanilloylquinic acid or burkinabin A; 3,5-O-divanilloylquinic acid or
      burkinabin B and 4,5-O-divanilloylquinic acid or burkinabin C) identified
      previously by LC/MS/NMR analysis in the root bark of F. zanthoxyloides [Ouattara
      et al., 2004. LC/MS/NMR analysis of isomeric divanilloylquinic acids from the
      root bark of Fagara zanthoxyloides Lam. Phytochemistry 65, 1145-1151]. The three
      isomers showed interesting antisickling properties which increased from
      burkinabins A to C.

PMID- 19110408
TI  - Exhaled cysteinyl-leukotrienes and 8-isoprostane in patients with asthma and
      their relation to clinical severity.
AB  - BACKGROUND: Collection of exhaled breath condensate (EBC) is a safe, non-invasive
      method to collect droplets of the airway surface liquid and measure mediators of
      airway inflammation and oxidative stress, such as cysteinyl-leukotrienes (cys
      LTs) and 8-isoprostane. OBJECTIVE: The aim of our study was to investigate
      baseline values of inflammatory lipid mediators in EBC and their relation to
      asthma severity. METHODS: Nineteen healthy subjects, 16 mild, 12 moderate and 15
      severe asthmatics were studied. All subjects attended a clinic visit for
      spirometry and EBC collection. The concentrations of exhaled cys-LTs and 8
      isoprostane were measured by means of specific enzyme immunoassays. RESULTS: 8
      isoprostane levels were significantly increased in mild (49.1+/-5.2 pg/mL,
      p<0.001), moderate (49.7+/-5.2 pg/mL, p<0.001) and severe asthmatics (77.7+/-7.3
      pg/mL, p<0.001), compared to healthy controls (16.4+/-1.6 pg/mL). Moreover, 8
      isoprostane levels were significantly higher in severe compared to mild and
      moderate asthmatics (p<0.01). Cys-LT levels were significantly higher in moderate
      (34.6+/-4.4 pg/mL, p<0.05) and severe asthmatics (47.9+/-6.0 pg/mL, p<0.001),
      while no significant difference was found between healthy controls and mild
      asthmatics. 8-isoprostane levels in EBC of asthmatics strongly correlated with
      cys-LT levels (r=0.61, p<0.0001). CONCLUSIONS: 8-isoprostane and cys-LT are
      detectable in EBC of healthy subjects and their levels progressively increase in
      asthmatic patients according to disease severity. The correlation found between
      these two lipid mediators indicating a link between oxidative stress and airway
      inflammation.

PMID- 19110409
TI  - Poverty as a smoking trap.
AB  - BACKGROUND: The relationship between smoking and poverty is a public health issue
      in many countries, and several studies have shown a link between living in
      deprived neighbourhoods and smoking. In France the prevalence of smoking has
      decreased since the year 2000s. We examined whether reduced smoking rates
      differed by socio-economic status, anticipating reductions to be smaller amongst
      lower socio-economic groups. We also investigated whether poor housing conditions
      and/or living in a deprived neighbourhood were significantly associated with
      smoking. METHODS: Data were collected by telephone surveys conducted between 2000
      and 2007 with representative samples of the French population aged 18-75. The
      data from the last of these surveys (2007, N=6007) were also used to carry out a
      cluster analysis on various indicators relating to housing conditions and
      neighbourhood. RESULTS: Between 2000 and 2007 the social differential in smoking
      rates increased sharply in France. Specific types of neighbourhood and poor
      housing conditions (described as cramped housing in a noisy and stressful
      environment or deprived neighbourhood), which were closely correlated with socio
      economic status, were found to be significantly correlated with smoking, even
      after adjusting for potential key confounders and especially for individual
      markers of social disadvantage. CONCLUSION: Interventions which do not
      specifically target smoking but which contribute to improving poor smokers'
      living conditions, are necessary to promote smoking cessation.

PMID- 19110410
TI  - Possibility of using waste tire rubber and fly ash with Portland cement as
      construction materials.
AB  - The growing amount of waste rubber produced from used tires has resulted in an
      environmental problem. Recycling waste tires has been widely studied for the last
      20 years in applications such as asphalt pavement, waterproofing systems and
      membrane liners. The aim of this study is to evaluate the feasibility of
      utilizing fly ash and rubber waste with Portland cement as a composite material
      for masonry applications. Class C fly ash and waste automobile tires in three
      different sizes were used with Portland cement. Compressive and flexural
      strength, dry unit weight and water absorption tests were performed on the
      composite specimens containing waste tire rubber. The compressive strength
      decreased by increasing the rubber content while increased by increasing the fly
      ash content for all curing periods. This trend is slightly influenced by particle
      size. For flexural strength, the specimens with waste tire rubber showed higher
      values than the control mix probably due to the effect of rubber fibers. The dry
      unit weight of all specimens decreased with increasing rubber content, which can
      be explained by the low specific gravity of rubber particles. Water absorption
      decreased slightly with the increase in rubber particles size. These composite
      materials containing 10% Portland cement, 70% and 60% fly ash and 20% and 30%
      tire rubber particles have sufficient strength for masonry applications.

PMID- 19110411
TI  - Electrochemiluminescence detection of NADH and ethanol based on partial
      sulfonation of sol-gel network with gold nanoparticles.
AB  - We developed a stable, sensitive electrochemiluminescence (ECL) biosensor based
      on the synthesis of a new sol-gel material with the ion-exchange capacity sol-gel
      to coimmobilize the Ru(bpy)(3)(2+) and enzyme. The partial sulfonated (3
      mercaptopropyl)-trimethoxysilane sol-gel (PSSG) film acted as both an ion
      exchanger for the immobilization of Ru(bpy)(3)(2+) and a matrix to immobilize
      gold nanoparticles (AuNPs). The AuNPs/PSSG/Ru(bpy)(3)(2+) film modified electrode
      allowed sensitive the ECL detection of NADH as low as 1 nM. Such an ability of
      AuNPs/PSSG/Ru(bpy)(3)(2+) film to promote the electron transfer between
      Ru(bpy)(3)(2+) and the electrode suggested a new, promising biocompatible
      platform for the development of dehydrogenase-based ECL biosensors. With alcohol
      dehydrogenase (ADH) as a model, we then constructed an ethanol biosensor, which
      had a linear range of 5 microM to 5.2 mM with a detection limit of 12nM.

PMID- 19110412
TI  - A micro-potentiometric hemoglobin immunosensor based on electropolymerized
      polypyrrole-gold nanoparticles composite.
AB  - We report a novel micro-potentiometric hemoglobin (Hb) immunosensor based on
      electrochemically synthesized polypyrrole (PPy)-gold nanoparticles (AuNPs)
      composite. PPy-AuNPs film with AuNPs uniformly distributed in it was deposited on
      gold electrode surface by a simple and direct procedure, without the addition of
      any nanoparticles or reducing agent. And this generic method makes it possible to
      deposite different polymers on miniaturized electrodes. With the existence of
      AuNPs, the antibody immobilization onto the electrode surface was facilitated.
      Morphology study by field emission scanning electron microscope (FE-SEM) confirms
      the presence of AuNPs in PPy. Based on an ion-sensitive field-effect transistors
      (ISFETs) integrated chip, a micro-potentiometric immunosensor for Hb and
      hemoglobin-A1c (HbA1c) has been constructed. The sensor response was linear over
      the concentration range 60-180 microg/ml Hb and 4-18 microg/ml HbA1c. The Hb
      concentration in whole blood samples has also been analysed, with a linear dose
      response behavior between 125 and 197 microg/ml and a sensitivity of 0.20 mV
      microg(-1)ml. The measuring ranges of the developed Hb and HbA1c immunosensors
      meet the clinical demand for measuring the HbA1c/Hb ratio of 5-20%. This sensor
      results in simple and rapid differential measurement of Hb and HbA1c, and has
      great potential to become an inexpensive and portable device for monitoring of
      diabetes.

PMID- 19110413
TI  - Development of an open stand-alone platform for regenerable automated
      microarrays.
AB  - A novel automated chemiluminescence (CL) read-out system for analytical flow
      through microarrays based on multiplexed immunoassays has been developed. The
      microarray chip reader (MCR 3) is designed as a stand-alone platform, with the
      goal to quantify multiple analytes in complex matrices of food and liquid samples
      for field analysis or for routine analytical laboratories. The CL microarray
      platform is a self-contained system for the fully automated multiplexed
      immunoanalysis: the microarray chip, the fluidic system and the software module
      enable automated calibration and determination of analyte concentrations during a
      whole working day. The detection of antibiotics in milk was demonstrated to
      validate this device. There are few quantitative multi-residue detection methods
      for routine analysis although the EU has defined maximum residue limits (MRLs)
      for a number of antibacterial reagents. Therefore, an automated multianalyte
      detection instrument is needed quantifying simultaneously antibiotics within some
      minutes. Also regeneration is required to avoid replacing the assay surface. The
      MCR 3 uses a microarray chip, which consists of two channels for parallel
      measurement and regeneration. The microarray chip is designed for parallel
      analysis of up to 13 different antibiotics in milk applying an indirect
      competitive microarray immunoassay (MIA). Microspotted antibiotics are directly
      coupled to epoxylated PEG surfaces. As an initial example, penicillin G is
      quantified in milk on the MCR 3. The penicillin G surface is regenerable for 47
      measurement cycles per channel. A limit of detection (LOD) of 1.1 microg/L is
      achieved by an assay time of 6 min.

PMID- 19110414
TI  - Quantitative analysis of enhanced light irradiance in waveguide-based fluorescent
      microarrays.
AB  - Probing microarray assays in the presence of a hybridization mix retrieves
      precious information on hybridization kinetics. However, in common detection
      schemes, useful surface signals compete with the high supernatant background from
      labelled targets in the mix. A known solution consists in exciting specifically
      the microarray surface with evanescent fields. Configurations using planar
      optical waveguides to produce such fields are shown here to present also a
      dramatic excitation irradiance enhancement at the guide/surrounding matter
      interface. We compare theoretically and experimentally a guided excitation with a
      classical external excitation. A full electromagnetic analysis predicts an
      irradiance increase higher than 10(4) for adequately tailored waveguides. We
      deposited high-index TiO(2) sol-gel waveguides on glass substrates according to
      best simulations. Quantitative enhancement analysis exploiting actual biological
      fluorescent spots perfectly confirms the irradiance amplification effect of a
      thin waveguide. The impact of amplification on the design of biochip readers is
      discussed since it leaves ample margin for simple and low-cost light couplers,
      advantageous in affordable readers and sensor systems.

PMID- 19110415
TI  - Febrile neutropenia and related complications in breast cancer patients receiving
      pegfilgrastim primary prophylaxis versus current practice neutropaenia
      management: results from an integrated analysis.
AB  - Granulocyte colony-stimulating factors (G-CSFs) reduce febrile neutropaenia (FN)
      incidence but may be used inconsistently in current practice (CP). This study
      compared the efficacy of pegfilgrastim primary prophylaxis (PPP) with CP
      neutropaenia management in breast cancer. Individual patient data (N=2282) from
      11 clinical trials and observational studies using chemotherapy regimens with >
      or =15% FN risk and PPP (6 mg, all cycles) or CP (no G-CSF or any cycle G
      CSF/pegfilgrastim) were included in an integrated analysis. Most patients
      received docetaxel-containing regimens. A generalised linear mixed model was
      fitted (N=2210). Neutropaenia prophylaxis (PPP versus CP), age and disease stage
      influenced the incidence of FN. Overall, FN was less frequent with PPP than with
      CP (odds ratio [OR]: 0.124; 95% confidence interval [CI]: 0.08, 0.194; P<0.0001).
      Odds for cycle 1 FN, dose reductions > or =15% and FN-related hospitalisation
      were also significantly lower with PPP. These data support PPP in breast cancer
      patients receiving chemotherapy with moderately high/high FN risk.

PMID- 19110416
TI  - Multicentre phase II trial of capecitabine and oxaliplatin in combination with
      radiotherapy for unresectable colorectal cancer: the CORGI-L Study.
AB  - AIMS: This study assessed radiotherapy combined with capecitabine and oxaliplatin
      in patients with primary, inextirpable colorectal adenocarcinoma. PATIENTS AND
      METHODS: Forty-nine patients entered the trial. Two cycles of XELOX (capecitabine
      1000 mg/m(2) bid d1-14+oxaliplatin 130 mg/m(2) d1, q3w) were followed by
      radiotherapy (50.4 Gy), combined with capecitabine 825 mg/m(2) bid every
      radiotherapy day and oxaliplatin 60 mg/m(2) once weekly. The primary end-point
      was objective response. RESULTS: Forty-seven patients were evaluable. Twenty-nine
      (62% [95% CI: 46-75%]) achieved complete or partial response. Thirty-eight (81%)
      went through surgery of whom 37 (97%) had an R0 resection and five (13%) had a
      pathological complete response. Seventy-eight percent were alive and estimated
      local progression rate was 11% at 2 years. The most common grade 3+ toxicity
      during chemoradiotherapy was diarrhoea (24%). CONCLUSIONS: XELOX-RT was feasible
      and showed promising efficacy when treating patients with primary inextirpable
      colorectal cancer, establishing high local control rate.

PMID- 19110417
TI  - Common genetic variations of the cytochrome P450 1A1 gene and risk of
      hepatocellular carcinoma in a Chinese population.
AB  - Cytochrome P450 1A1 is a major enzyme in the bioactivation of exogenous
      procarcinogens of hepatocellular carcinoma (HCC). However, the contribution of
      common genetic variants in CYP1A1 to the HCC risk in Chinese populations has not
      been thoroughly investigated. In this study, we examined the association between
      HCC and four selected tagging single nucleotide polymorphisms (SNPs) of CYP1A1,
      and the risk of CYP1A1 haplotypes/diplotypes in 1006 pathologically confirmed HCC
      patients and 1015 cancer-free controls, from a Han Chinese population.
      Haplotypes/diplotypes were constructed from observed genotypes using the
      Haplo.Stats program. Relative risk was estimated by using multivariable logistic
      regression method. To summarise, we detected an increased HCC risk in rs4646421
      variant carriers (OR 1.30, 95% CI 1.05-1.61) and rs2198843 variant carriers (OR
      1.33, 95% CI 1.05-1.69), and a reduced risk of HCC (OR 0.70. 95% CI 0.52-0.94)
      associated with homozygote carriers of rs4886605 variant. These association
      signals were also observed in non-smokers with rs4646421 (OR 1.56, 95% CI 1.16
      2.08) and rs4886605 (OR 0.61, 95% CI 0.40-0.91). Compared to the most common
      CYP1A1 haplotype CCAG, the haplotype TTGC conferred an increased risk of HCC (OR
      1.26, 95% CI 1.04-1.52). Similarly, the TTGC/TTGC diplotype conferred an
      increased risk of HCC compared with diplotype CCAG/CCAG (OR 2.06, 95% CI 1.23
      3.45, P=0.006). Interestingly, the diplotype TTAC/CCAG also conferred an
      increased risk of HCC (OR 1.76, 95% CI 1.22-2.54, P=0.003). Our results suggested
      that common genetic variants in CYP1A1 may modulate the risk of developing HCC in
      the study population, particularly in non-smokers. However, our findings need to
      be validated in at least one independent study of Han Chinese population.

PMID- 19110418
TI  - N.O.T.E.S.: the progression of a novel and emerging technique.
AB  - Natural Orifice Transluminal Endoscopic Surgery (NOTES) is the latest and perhaps
      most significant innovation in surgery since Phillipe Mouret of France performed
      the first laparoscopic cholecystectomy in 1987. This new "minimum-invasive"
      concept that promises scar-free surgery is steadily gathering momentum. It is
      another milestone in our quest to eliminate surgical trauma, speed patient
      recovery time and decrease surgical wound-related complications. On 22 July 2005,
      the Natural Orifice Surgery Consortium for Assessment and Research (NOSCAR)
      published a white paper highlighting the barriers to NOTES development, which
      included the need for appropriate selection of access points, effective closure
      of the enterotomy site, innovative tools, stable platforms and improved
      endoscopic orientation. These are just some of the many issues that need to be
      resolved before the NOTES concept and technique could become a common feature of
      modern surgery. The publication of the white paper ushered in the beginning of
      multiple research projects using animal models to test the application of NOTES
      and its newly developed instruments. The success in animal models was followed by
      several highly selected successful human trials. National and international
      surgical innovation departments should now be created where medical industry
      personnel including inventors, designers and engineers can work together with the
      medical and surgical providers to address all the limitations affecting NOTES
      progress.

PMID- 19110419
TI  - In vitro anti-inflammatory activity of lignans isolated from Magnolia fargesii.
AB  - The overproduction of nitric oxide (NO) and prostaglandin E(2) (PGE(2)) causes
      neurodegenerative diseases, such as Alzheimer's disease and Parkinson's disease.
      Four lignans, (+)-eudesmin (1), (+)-magnolin (2), (+)-yangambin (3) and a new
      structure named as epimagnolin B (4) were isolated from Magnolia fargesii
      (Magnoliaceae) as the inhibitors of NO production in LPS-activated microglia. The
      most potent compound 4 inhibited the production of NO and PGE(2) and the
      expression of respective enzyme iNOS and COX-2 through the suppression of I
      kappaB-alpha degradation and nuclear translocation of p65 subunit of NF-kappaB.

PMID- 19110420
TI  - Synthesis and structure-activity relationships of novel, substituted 5,6
      dihydrodibenzo[a,g]quinolizinium P2X7 antagonists.
AB  - Iminium quaternary protoberberine alkaloids (QPA) have been found to be novel
      P2X(7) antagonists. To assess their structure-activity relationships, these
      compounds were modified at their R(1) and R(2) groups and assayed for their
      ability to inhibit the 2'(3')-O-(4-benzoylbenzoyl)-ATP (BzATP)-induced uptake of
      fluorescent ethidium by HEK-293 cells stably expressing the human P2X(7)
      receptor, and their ability to inhibit BzATP-induced IL-1beta release by
      differentiated THP-1 cells. Compounds 15a and 15d, with alkyl groups at the R(1)
      position, and especially compound 19h, with the 2-NO(2)-4,5-dimethoxy-benzyl
      group at the R(2) position, had potent inhibitory efficacy as P2X(7) antagonists.

PMID- 19110422
TI  - 5-Substituted pyrido[2,3-d]pyrimidine, an inhibitor against three receptor
      tyrosine kinases.
AB  - NP506, the 3-{2,4-dimethyl-5-[2-oxo-5-(N'-phenylhydrazinocarbonyl)-1,2-dihydro
      indol-3-ylidenemethyl]-1H-pyrrol-3-yl}-propionic acid, was designed as FGF
      receptor 1 inhibitor by computational study and found to be more active against
      endothelial proliferation of HUVEC after the rhFGF-2 stimulation than SU6668 with
      minimum effective dose of 10 microM. NP506 inhibited the tyrosine phosphorylation
      in FGF, VEGF, and PDGF receptors and the activation of extracellular signal
      regulated kinase (ERK), c-Jun-N-terminal-kinase (JNK) and AKT after the rhFGF-2
      stimulation. The introduction of the phenyl hydrazide motif to the position 5 of
      the pyrido[2,3-d]pyrimidine scaffold led to the inhibitory effect in two
      signaling pathways: inhibition of AKT activation in the phosphatidyl inositol 3'
      kinase (PI13K)/AKT signaling pathway and the inhibition of ERK and JNK activation
      in MAPK pathway.

PMID- 19110421
TI  - A small molecule inhibitor selective for a variant ATP-binding site of the
      chaperonin GroEL.
AB  - The chaperonin GroEL is a megadalton-sized molecular machine that plays an
      essential role in the bacterial cell assisting protein folding to the native
      state through actions requiring ATP binding and hydrolysis. A combination of
      medicinal chemistry and genetics has been employed to generate an orthogonal
      pair, a small molecule that selectively inhibits ATPase activity of a GroEL ATP
      binding pocket variant. An initial screen of kinase-directed inhibitors
      identified an active pyrazolo-pyrimidine scaffold that was iteratively modified
      and screened against a collective of GroEL nucleotide pocket variants to identify
      a cyclopentyl carboxamide derivative, EC3016, that specifically inhibits ATPase
      activity and protein folding by the GroEL mutant, I493C, involving a side chain
      positioned near the base of ATP. This orthogonal pair will enable in vitro
      studies of the action of ATP in triggering activation of GroEL-mediated protein
      folding and might enable further studies of GroEL action in vivo. The approach
      originated for studying kinases by Shokat and his colleagues may thus also be
      used to study large macromolecular machines.

PMID- 19110423
TI  - Selective fluorescence quenching of the 8-oxoG-clamp by 8-oxodeoxyguanosine in
      ODN.
AB  - The 8-oxoG-clamp, a specific fluorescent probe for 8-oxo-deoxyguanosine (8-oxo
      dG), was incorporated into the oligodeoxynucleotide (ODN) within or at the 3'-end
      of the purine and the pyrimidine sequences. Based on the UV-melting temperature,
      the 8-oxoG-clamp showed slightly lower stabilizing effects on the duplexes
      containing 8-oxo-dG at the complementary site than that with dG. On the other
      hand, 8-oxo-dG in DNA was selectively detected by fluorescence quenching of the 8
      oxoG-clamp.

PMID- 19110424
TI  - Synthesis and antifungal activity of 1,2,3-triazole containing fluconazole
      analogues.
AB  - Fluconazole based novel mimics containing 1,2,3-triazole were designed and
      synthesized as antifungal agents. Their antifungal activities were evaluated in
      vitro by measuring the minimal inhibitory concentrations (MICs). Compounds 12,
      15, and 16 were found to be more potent against Candida fungal pathogens than
      control drugs fluconazole and amphotericin B. The studies presented here provide
      structural modification of fluconazole to give 1,2,3-trazole containing
      molecules. Furthermore, these molecules were evaluated in vivo against Candida
      albicans intravenous challenge in Swiss mice and antiproliferative activities
      were tested against human hepatocellular carcinoma Hep3B and human epithelial
      carcinoma A431. It was found that compound 12 resulted in 97.4% reduction in
      fungal load in mice and did not show any profound proliferative effect at lower
      dose (0.001 mg/ml).

PMID- 19110425
TI  - Immediate reconstruction following breast-conserving surgery: management of the
      positive surgical margins and influence on secondary reconstruction.
AB  - The efficacy of breast-conserving surgery for the local control of early breast
      cancer has been repeatedly evidenced. Although immediate reconstruction following
      breast-conserving surgery has been described, little information is available
      regarding surgical management in reoperative settings due to positive margins. We
      studied the influence of intraoperatively assessed and postoperatively controlled
      surgical margin status on the type of breast-conserving surgery and report our
      results regarding complications in a reoperative breast reconstruction scenario.
      All patients were seen by a multidisciplinary team who recommended breast
      conserving surgery. According to the breast volume, ptosis and tumor
      size/location, the patients were also evaluated by a plastic surgeon, who
      recommended reconstruction with the appropriate technique. Intraoperative
      assessment of surgical margins was determined by histological examination of
      frozen sections. The mean follow-up time was 48 months. Two hundred and eighteen
      patients (88.5%) underwent breast-conserving surgery and immediate
      reconstruction. Twelve (5.5%) patients had a positive tumor margin after review
      of the permanent section. All patients underwent re-exploration. In 1.3%, a
      second reconstructive technique was indicated and in 2.2% a skin-sparing
      mastectomy with total reconstruction was performed. Our findings support the
      important role of the intraoperative assessment of surgical margins and its
      interference in the selection of reconstruction techniques and negative margins;
      however, it will not guarantee complete excision of the tumor. Success depends on
      coordinated planning with the oncologic surgeon and careful intraoperative
      management.

PMID- 19110426
TI  - Direct evidence for distance measurement via flexible stride integration in the
      fiddler crab.
AB  - While on foraging excursions, fiddler crabs track their burrow location despite
      having no visual contact with it . They do this by path integration, a common
      navigational process in which motion vectors (the direction and distance of
      animals' movements) are summed to form a single "home vector" linking the current
      location with the point of origin. Here, we identify the mechanism by which the
      integrator measures distance, by decoupling motor output from both inertial and
      visual feedback. Fiddler crabs were passively translated to a position such that
      the home vector lay across an acetate sheet on the ground. After being
      frightened, crabs tried to escape but slipped as they did so. Detailed high-speed
      video analysis reveals that crabs measure distance by integrating strides, rather
      than linear acceleration or optic flow: the number of steps they took depended on
      both the length of the home vector and how large their steps were, whether they
      slipped and fell short or not. This is the most direct evidence to date of a
      stride integrator that is flexible enough to account for significant variation in
      stride length and frequency.

PMID- 19110427
TI  - A novel vertebrate eye using both refractive and reflective optics.
AB  - Sunlight is attenuated rapidly in the ocean, resulting in little visually useful
      light reaching deeper than approximately 1000 m in even the clearest water. To
      maximize sensitivity to the relatively brighter downwelling sunlight, to view the
      silhouette of animals above them, and to increase the binocular overlap of their
      eyes, many mesopelagic animals have developed upward-pointing tubular eyes.
      However, these sacrifice the ability to detect bioluminescent and reflective
      objects in other directions. Thus, some mesopelagic fish with tubular eyes extend
      their visual fields laterally and/or ventrally by lensless ocular diverticula,
      which are thought to provide unfocused images, allowing only simple detection of
      objects, with little spatial resolution. Here, we show that a medial mirror
      within the ventrally facing ocular diverticulum of the spookfish, Dolichopteryx
      longipes, consisting of a multilayer stack derived from a retinal tapetum, is
      used to reflect light onto a lateral retina. The reflective plates are not
      orientated parallel to the surface of the mirror. Instead, plate angles change
      progressively around the mirror, and computer modeling indicates that this
      provides a well-focused image. This is the first report of an ocular image being
      formed in a vertebrate eye by a mirror.

PMID- 19110428
TI  - Regulation of LKB1/STRAD localization and function by E-cadherin.
AB  - LKB1 kinase is a tumor suppressor that is causally linked to Peutz-Jeghers
      syndrome. In complex with the pseudokinase STRAD and the scaffolding protein
      MO25, LKB1 phosphorylates and activates AMPK family kinases, which mediate many
      cellular processes. The prototypical family member AMPK regulates cell energy
      metabolism and epithelial apicobasal polarity. This latter event is also
      dependent on E-cadherin-mediated adherens junctions (AJs) at lateral borders.
      Strikingly, overexpression of LKB1/STRAD can also trigger establishment of
      epithelial polarity in the absence of cell-cell or cell-matrix contacts. However,
      the upstream factors that normally govern LKB1/STRAD function are unknown. Here
      we show by immunostaining and fluorescence resonance energy transfer that active
      LKB1/STRAD kinase complex colocalizes with E-cadherin at AJs. LKB1/STRAD
      localization and AMPK phosphorylation require E-cadherin-dependent maturation of
      AJs. However, LKB1/STRAD complex kinase activity is E-cadherin independent. These
      data suggest that in polarized epithelial cells, E-cadherin regulates AMPK
      phosphorylation by controlling the localization of the LKB1 complex. The LKB1
      complex therefore appears to function downstream of E-cadherin in tumor
      suppression.

PMID- 19110429
TI  - Cuckoo fungus mimics termite eggs by producing the cellulose-digesting enzyme
      beta-glucosidase.
AB  - Insects and fungi share a long history of association in various habitats,
      including the wood-decomposition niche. Fungal mimicry of termite eggs is one of
      the most striking evolutionary consequences of insect-fungus association.
      Termites of the genus Reticulitermes often harbor fungal sclerotia, called
      "termite balls," along with eggs in nursery chambers, whereby the fungus gains a
      competitor-free habitat in termite nests. Sophisticated morphological and
      chemical camouflage are needed for the fungus to mimic termite eggs. However, the
      mechanism of chemical egg mimicry by the fungus is unknown. Here, we show that
      the fungus mimics termite eggs chemically by producing the cellulose-digesting
      enzyme beta-glucosidase. We found that the termite egg-recognition pheromone
      consists of beta-glucosidase and lysozyme. Both enzymes are major salivary
      compounds in termites and are also produced in termite eggs. Termite balls were
      tended by termites only when the fungus produced beta-glucosidase. Our results
      demonstrated that the overlap of the cellulose digestion niche between termites
      and the fungus sharing the same chemicals provided the opportunity for the origin
      of termite egg mimicry by the fungus. This suggests that pheromone compounds
      might have originally evolved within other life history contexts, only later
      gaining function in chemical communication.

PMID- 19110430
TI  - Lack of DREAM protein enhances learning and memory and slows brain aging.
AB  - Memory deficits in aging affect millions of people and are often disturbing to
      those concerned. Dissection of the molecular control of learning and memory is
      paramount to understand and possibly enhance cognitive functions. Old-age memory
      loss also has been recently linked to altered Ca(2+) homeostasis. We have
      previously identified DREAM (downstream regulatory element antagonistic
      modulator), a member of the neuronal Ca(2+) sensor superfamily of EF-hand
      proteins, with specific roles in different cell compartments. In the nucleus,
      DREAM is a Ca(2+)-dependent transcriptional repressor, binding to specific DNA
      signatures, or interacting with nucleoproteins regulating their transcriptional
      properties. Also, we and others have shown that dream mutant (dream(-/-)) mice
      exhibit marked analgesia. Here we report that dream(-/-) mice exhibit markedly
      enhanced learning and synaptic plasticity related to improved cognition.
      Mechanistically, DREAM functions as a negative regulator of the key memory factor
      CREB in a Ca(2+)-dependent manner, and loss of DREAM facilitates CREB-dependent
      transcription during learning. Intriguingly, 18-month-old dream(-/-) mice display
      learning and memory capacities similar to young mice. Moreover, loss of DREAM
      protects from brain degeneration in aging. These data identify the Ca(2+)
      regulated "pain gene" DREAM as a novel key regulator of memory and brain aging.

PMID- 19110431
TI  - A conserved endocrine mechanism controls the formation of dauer and infective
      larvae in nematodes.
AB  - Under harsh environmental conditions, Caenorhabditis elegans larvae undergo
      arrest and form dauer larvae that can attach to other animals to facilitate
      dispersal. It has been argued that this phenomenon, called phoresy, represents an
      intermediate step toward parasitism. Indeed, parasitic nematodes invade their
      hosts as infective larvae, a stage that shows striking morphological similarities
      to dauer larvae. Although the molecular regulation of dauer entry in C. elegans
      involves insulin and TGF-beta signaling, studies of TGF-beta orthologs in
      parasitic nematodes didn't provide evidence for a common origin of dauer and
      infective larvae. To identify conserved regulators between Caenorhabditis and
      parasitic nematodes, we used an evolutionary approach involving Pristionchus
      pacificus as an intermediate. We show by mutational and pharmacological analysis
      that Pristionchus and Caenorhabditis share the dafachronic acid-DAF-12 system as
      the core endocrine module for dauer formation. One dafachronic acid, Delta7-DA,
      has a conserved role in the mammalian parasite Strongyloides papillosus by
      controlling entry into the infective stage. Application of Delta7-DA blocks
      formation of infective larvae and results in free-living animals. Conservation of
      this small molecule ligand represents a fundamental link between dauer and
      infective larvae and might provide a general strategy for nematode parasitism.

PMID- 19110433
TI  - Biomechanical characteristics of the knee joint in female athletes during tasks
      associated with anterior cruciate ligament injury.
AB  - This study was designed to compare biomechanical characteristics of the knee
      joint for several athletic tasks to elucidate their effects and to examine what
      tasks pose a risk for ACL injury. Three athletic tasks were performed by 24
      female athletes: single-limb landing, plant and cutting, and both-limb jump
      landing. Angular displacements of flexion/extension, abduction/adduction, and
      external/internal tibial rotation were calculated. Angular excursion and the rate
      of excursion of abduction and internal tibial rotation were also calculated.
      During plant and cutting, from foot contact, subjects rotated the tibia more
      rapidly and to a greater degree toward internal tibial rotation. Moreover,
      excursion of knee abduction is greater than that during single-limb landing.
      During both-limb jump landing, the knee flexion at foot contact was greater than
      for either single-limb landing or plant and cutting; peak knee abduction was
      greater than for either single-limb landing or plant and cutting. In plant and
      cutting, the risk of ACL injury is increased by greater excursion and more rapid
      knee abduction than that which occurs in single-limb landing, in addition to
      greater internal tibial rotation. Although single-limb tasks apparently pose a
      greater risk for ACL injury than bilateral landings, both-limb landing with
      greater knee abduction might also risk ACL injury.

PMID- 19110432
TI  - Temporal and spatial control of germ-plasm RNAs.
AB  - In many species, germ cells form in a specialized germ plasm, which contains
      localized maternal RNAs. In the absence of active transcription in early germ
      cells, these maternal RNAs encode germ-cell components with critical functions in
      germ-cell specification, migration, and development. For several RNAs,
      localization has been correlated with release from translational repression,
      suggesting an important regulatory function linked to localization. To address
      the role of RNA localization and translational control more systematically, we
      assembled a comprehensive set of RNAs that are localized to polar granules, the
      characteristic germ-plasm organelles. We find that the 3'-untranslated regions
      (UTRs) of all RNAs tested control RNA localization and instruct distinct temporal
      patterns of translation of the localized RNAs. We demonstrate necessity for
      translational timing by swapping the 3'UTR of polar granule component (pgc),
      which controls translation in germ cells, with that of nanos, which is translated
      earlier. Translational activation of pgc is concurrent with extension of its
      poly(A) tail length but appears largely independent of the Drosophila CPEB
      homolog ORB. Our results demonstrate a role for 3'UTR mediated translational
      regulation in fine-tuning the temporal expression of localized RNA, and this may
      provide a paradigm for other RNAs that are found enriched at distinct cellular
      locations such as the leading edge of fibroblasts or the neuronal synapse.

PMID- 19110434
TI  - Synthesis, trypanocidal activity and docking studies of novel quinoxaline-N
      acylhydrazones, designed as cruzain inhibitors candidates.
AB  - In this paper, we report the structural design, synthesis, trypanocidal activity
      and docking studies of novel quinoxaline-N-acylhydrazone (NAH) derivatives,
      planned as cruzain inhibitors candidates, a cysteine protease essential for the
      survival of Trypanosoma cruzi within the host cell. The salicylaldehyde N
      acylhydrazones 7a and 8a presented IC(50) values of the same magnitude order than
      the standard drug nifurtimox (Nfx), when tested in vitro against epimastigote
      forms of Trypanosoma cruzi (Tulahuen 2 strain) and were non-toxic at the highest
      assayed doses rendering selectivity indexes (IC(50) (macrophages)/IC(50)
      (Trypanosoma cruzi)) of >25 for 7a and >20 for 8a, with IC(50) values in
      macrophages >400 microM.

PMID- 19110435
TI  - Computational comparison of the conventional multislice method and the real space
      multislice method for simulating exit wavefunctions.
AB  - The simulation of exit wavefunctions of a TEM sample is carried out by both the
      conventional multislice (C-MS) method and the real space multislice (RS-MS)
      method, with a series of different slice thicknesses. Surprisingly, the results
      calculated by the RS-MS method remain constant to seven significant figures when
      the slice thicknesses are changed within a wide range, while those calculated by
      the C-MS method change significantly. From the mathematical point of view, the C
      MS method is only a first order approximation of the RS-MS method. Thus, the
      calculation precision of the RS-MS method is much higher than that of the C-MS
      method. Or to achieve the same precision, the slice thickness for the RS-MS
      method can be taken as two orders of magnitude larger than for the C-MS method in
      the simulation. As a result, the calculation speed for the RS-MS method may be
      even faster than that for the C-MS method in some cases. For the two advantages
      stated above, the RS-MS method may be more suitable for precise calculations.

PMID- 19110436
TI  - Excitation functions of proton-induced reactions in (nat)Cu in the energy range 7
      17 MeV.
AB  - Elemental production cross sections were measured for (p,x) reactions on natural
      Cu targets, leading to the formation of (62,63,65)Zn. These reactions are
      generally used for monitoring the proton beam intensity and energy e.g. in
      isotope production facilities. Cross sections were obtained by activation of
      stacked foils and subsequent gamma spectroscopy. The production data for
      (62,63,65)Zn between 7 and 16.5 MeV proton energy are presented as well as
      comparisons with literature values. Good agreement with the evaluated values was
      found for most of the cross-section values.

PMID- 19110437
TI  - Targetry of SrCO(3) on a copper substrate by sedimentation method for the
      cyclotron production no-carrier-added (86)Y.
AB  - Strontium carbonate deposition on copper substrate was carried out by the
      sedimentation method in order to produce yttrium-86. Natural strontium carbonate
      thick layer was prepared with 480 mg SrCO(3), 220 mg ethyl cellulose, and 7.5 mL
      acetone. This optimum condition is a result of several repeated experiments with
      different amount of ethyl cellulose and acetone. Target quality control was done
      by SEM photomicrograph and thermal shock test. The deposited target was
      irradiated at 30 microA current and 15 MeV proton beam for 12 min.

PMID- 19110438
TI  - Isolated surgical aortic valve replacement after previous coronary artery bypass
      grafting with patent grafts: is this old-fashioned technique obsolete?
AB  - AIM: High-risk patients are currently being evaluated for various catheter-based
      aortic valve replacement (AVR) techniques. To identify an individual patient's
      risk, scores such as the EuroSCORE or STS risk calculator (RC) are used. The aim
      of the present study was to evaluate the surgical results in patients who
      underwent isolated AVR via a median re-sternotomy after prior CABG. PATIENTS AND
      METHODS: Between 01/96 and 01/08, 349 patients underwent AVR as a redo procedure.
      One hundred and thirty patients had undergone previous CABG; in 39 patients (29
      male, median age 75 (60-84)) preoperative coronary angiography revealed open
      grafts with no need for additional revascularization (30 had LIMA grafts). These
      patients underwent isolated AVR. Operative mortality was calculated using the
      standard and logistic EuroSCORE, and the STS RC. RESULTS: Operative (30-day
      mortality) was 5% (2 patients). Mean calculated predicted mortality rates for the
      cohort were: 12+/-3% for the standard, and 32+/-21% for the logistic EuroSCORE,
      and 10+/-4% according to the STS RC. Receiver operated characteristics (ROC)
      analysis revealed 100% specificity for standard EuroSCOREs up to 12.5%, logistic
      EuroSCOREs up to 39.7% and up to 17.45% for STS RC, with a sensitivity of 69.5%,
      75% and 97.2%, respectively. The STS RC showed significant better prediction of
      mortality than the EuroSCOREs (p=0.006). CONCLUSIONS: Conventional AVR as a redo
      procedure after CABG with patent grafts can be performed with excellent results
      and lower mortality than estimated. Results of newer catheter-based AVR
      approaches should not to be compared with artificial scores to justify high
      morbidity rates.

PMID- 19110439
TI  - Effusive constrictive pericarditis: dynamic magnetic resonance imaging.

PMID- 19110440
TI  - Collisional activation of protein complexes: picking up the pieces.
AB  - Mass spectrometry is fast becoming a vital approach not only for the
      identification and quantification of proteins, but also for the study of the
      noncovalent assemblies they form. Approaches for ionizing, transmitting, and
      detecting protein complexes intact in the mass spectrometer are now well
      established. The challenge has therefore shifted to developing and applying mass
      spectrometry approaches to elucidate the structure of such species. A crucial
      aspect to this goal is inducing their disassembly in the gas phase to mine
      information as to their composition and organization. Here the consequences of
      collisionally activating protein complexes are illustrated through ion mobility
      mass spectrometry measurements and discussed in the context of the current
      literature. Although a consensus view of the mechanism of dissociation is
      starting to emerge, it is also clear that a number of aspects remain unresolved.
      These outstanding questions and frontier challenges must be addressed if gas
      phase dissociative approaches are to reach their full potential in the study of
      protein assemblies.

PMID- 19110441
TI  - The evaluation and comparison of trigonal and linear tricationic ion-pairing
      reagents for the detection of anions in positive mode ESI-MS.
AB  - A general and sensitive method for detecting divalent anions by ESI-MS and LC/ESI
      MS as positive ions has been developed. The anions are paired with tricationic
      reagents to form positively charged complexes. In this study, four tricationic
      reagents, 2 trigonal and 2 linear, were used to study a wide variety of anions,
      such as disulfonates, dicarboxylates, and inorganic anions. The limits of
      detection for many of the anions studied were often improved by tandem mass
      spectrometry. Tricationic pairing agents can also be used with chromatography to
      enhance the detection of anions. The tricationic reagents were also used to
      detect monovalent anions by monitoring the doubly charged positive complex. The
      limits of detection for some of the divalent anions by this method are
      substantially lower than by other current analytical techniques.

PMID- 19110442
TI  - Probing hemoglobin structure by means of traveling-wave ion mobility mass
      spectrometry.
AB  - Hemoglobin (Hb) is a tetrameric noncovalent complex consisting of two alpha- and
      two beta-globin chains each associated with a heme group. Its exact assembly
      pathway is a matter of debate. Disorders of hemoglobin are the most common
      inherited disorders and subsequently the molecule has been extensively studied.
      This work attempts to further elucidate the structural properties of the
      hemoglobin tetramer and its components. Gas-phase conformations of hemoglobin
      tetramers and their constituents were investigated by means of traveling-wave ion
      mobility mass spectrometry. Sickle (HbS) and normal (HbA) hemoglobin molecules
      were analyzed to determine whether conformational differences in their quaternary
      structure could be observed. Rotationally averaged collision cross sections were
      estimated for tetramer, dimer, apo-, and holo-monomers with reference to a
      protein standard with known cross sections. Estimates of cross section obtained
      for the tetramers were compared to values calculated from X-ray crystallographic
      structures. HbS was consistently estimated to have a larger cross section than
      that of HbA, comparable with values obtained from X-ray crystallographic
      structures. Nontetrameric species observed included apo- and holo- forms of alpha
      and beta-monomers and heterodimers; alpha- and beta-monomers in both apo- and
      holo- forms were found to have similar cross sections, suggesting they maintain a
      similar fold in the gas phase in both the presence and the absence of heme. Heme
      deficient dimer, observed in the spectrum when analyzing commercially prepared
      Hb, was not observed when analyzing fresh blood. This implies that holo-alpha-apo
      beta is not an essential intermediate within the Hb assembly pathway, as
      previously proposed.

PMID- 19110444
TI  - A simple model for the disintegration of highly charged solvent droplets during
      electrospray ionization.
AB  - This work uses a minimalist model for deciphering the opposing effects of Coulomb
      repulsion and surface tension on the stability of electrosprayed droplets. Guided
      by previous observations, it is assumed that progeny droplets are ejected from
      the tip of liquid filaments that are formed as protrusions of an initially
      spherical parent. Nonspherical shapes are approximated as assemblies of multiple
      closely spaced beads. This strategy greatly facilitates the calculation of
      electrostatic and surface energies. For a droplet at the Rayleigh limit the model
      predicts that growth of a very thin filament is a spontaneous process with a
      negligible activation barrier. In contrast, significant barriers are encountered
      for the formation of larger diameter filaments. These different barrier heights
      favor highly asymmetric droplet fission because the dimensions of the filament
      determine those of the ejected droplet(s). Substantial charge accumulation occurs
      at the filament termini. This allows each progeny droplet to carry a significant
      fraction of charge, despite its very small volume. In the absence of a long
      connecting filament, relieving electrostatic stress through progeny droplet
      emission would be ineffective. The model predicts the prevalence of fission
      events leading to the formation of several progeny droplets, instead of just a
      single one. Ejection bursts are followed by collapse back to a spherical shape.
      The resulting charge depleted system is incapable of producing additional progeny
      droplets until solvent evaporation returns it to the Rayleigh limit. Despite the
      very simple nature of the model used here, all of these predictions agree with
      experimental data.

PMID- 19110443
TI  - Investigation of calmodulin-Peptide interactions using matrix-assisted laser
      desorption/ionization mass spectrometry.
AB  - In this report, matrix-assisted laser desorption/ionization mass spectrometry
      (MALDI-MS) was used to study the binding interactions between calmodulin and two
      target peptides (melittin and substance P). Various matrix conditions were tested
      and the less acidic matrix DHAP and THAP were found to favor the survival of the
      intact calcium-calmodulin as well as the calmodulin-peptide complexes. However,
      the application of direct MALDI-MS to detect the intact complexes turned out to
      be very difficult due to the dissociation of the complexes and the formation of
      nonspecific aggregates. In contrast, the specific binding of the target peptides
      to calmodulin could be easily deduced using intensity-fading (IF) MALDI-MS.
      Compared with the nonbinding control, clear reduction in the ion abundances of
      the target peptides was observed with the addition of calmodulin. Relative
      binding affinities of different peptides towards the protein could also be
      estimated using IF-MALDI-MS. This study may extend the application of IF-MALDI-MS
      in the analysis of noncovalent complexes and offer a perspective into the utility
      of MALDI-MS as an alternative approach to study the peptides binding to
      calmodulin.

PMID- 19110446
TI  - Sesa syndrome: a subtype of localisation-related non-convulsive status
      epilepticus?

PMID- 19110445
TI  - Accurate localization and relative quantification of arginine methylation using
      nanoflow liquid chromatography coupled to electron transfer dissociation and
      orbitrap mass spectrometry.
AB  - Protein arginine (Arg) methylation serves an important functional role in
      eucaryotic cells, and typically occurs in domains consisting of multiple Arg in
      close proximity. Localization of methylarginine (MA) within Arg-rich domains
      poses a challenge for mass spectrometry (MS)-based methods; the peptides are
      highly charged under electrospray ionization (ESI), which limits the number of
      sequence-informative products produced by collision induced dissociation (CID),
      and loss of the labile methylation moieties during CID precludes effective
      fragmentation of the peptide backbone. Here the fragmentation behavior of Arg
      rich peptides was investigated comprehensively using electron-transfer
      dissociation (ETD) and CID for both methylated and unmodified glycine-/Arg-rich
      peptides (GAR), derived from residues 679-695 of human nucleolin, which contains
      methylation motifs that are widely-represented in biological systems. ETD
      produced abundant information for sequencing and MA localization, whereas CID
      failed to provide credible identification for any available charge state (z = 2
      4). Nevertheless, CID produced characteristic neutral losses that can be employed
      to distinguish among different types of MA, as suggested by previous works and
      confirmed here with product ion scans of high accuracy/resolution by an
      LTQ/Orbitrap. To analyze MA-peptides in relatively complex mixtures, a method was
      developed that employs nano-LC coupled to alternating CID/ETD for peptide
      sequencing and MA localization/characterization, and an Orbitrap for accurate
      precursor measurement and relative quantification of MA-peptide stoichiometries.
      As proof of concept, GAR-peptides methylated in vitro by protein arginine N
      methyltransferases PRMT1 and PRMT7 were analyzed. It was observed that PRMT1
      generated a number of monomethylated (MMA) and asymmetric-dimethylated peptides,
      while PRMT7 produced predominantly MMA peptides and some symmetric-dimethylated
      peptides. This approach and the results may advance understanding of the actions
      of PRMTs and the functional significance of Arg methylation patterns.

PMID- 19110447
TI  - The impact of side effects on long-term retention in three new antiepileptic
      drugs.
AB  - OBJECTIVE: To determine long-term retention, percentage of patients withdrawing
      because of adverse events, percentage of patients achieving seizure freedom,
      safety profile of the new anti-epileptic drugs lamotrigine, levetiracetam and
      topiramate. METHODS: All patients treated with lamotrigine, levetiracetam or
      topiramate in the Epilepsy Centre were identified. Each drug was analyzed from
      introduction of the drug in the Netherlands up to a final assessment point 2
      years later. RESULTS: Data from 1066 patients were included: 336 for lamotrigine,
      301 for levetiracetam, 429 for topiramate. Two-year retention rates were 69.2%
      (lamotrigine), 45.8% (levetiracetam), 38.3% (topiramate); (LTG vs. LEV at
      p<0.001; LTG vs. TPM at p<0.001; LEV vs. TPM at p=0.005). Seizure freedom rates
      were lowest for lamotrigine and highest for levetiracetam. Adverse events played
      a role in drug discontinuation in 154/429 patients (35.9%) on topiramate, 52/336
      patients (15.5%) on lamotrigine (p<0.001), 68/301 patients (22.5%) on
      levetiracetam (p<0.001). Mood and general CNS-effects are common in patients on
      lamotrigine and levetiracetam, and neurocognitive side effects are most prevalent
      in patients on topiramate. A positive effect on cognition is frequently noted in
      patients on lamotrigine. CONCLUSION: A drug that is only modestly efficacious but
      has a favourable safety profile may look better than a drug that is more
      efficacious but produces clinically meaningful adverse events. Therefore, a
      drug's retention rate is mainly determined by its side effect profile. As a
      consequence, retention rate was highest for lamotrigine and lowest for
      topiramate. Intermediate retention rates were seen with levetiracetam use.

PMID- 19110448
TI  - Deletion of Notch1 converts pro-T cells to dendritic cells and promotes thymic B
      cells by cell-extrinsic and cell-intrinsic mechanisms.
AB  - Notch1 signaling is required for T cell development and has been implicated in
      fate decisions in the thymus. We showed that Notch1 deletion in progenitor T
      cells (pro-T cells) revealed their latent developmental potential toward becoming
      conventional and plasmacytoid dendritic cells. In addition, Notch1 deletion in
      pro-T cells resulted in large numbers of thymic B cells, previously explained by
      T-to-B cell fate conversion. Single-cell genotyping showed, however, that the
      majority of these thymic B cells arose from Notch1-sufficient cells by a cell
      extrinsic pathway. Fate switching nevertheless exists for a subset of thymic B
      cells originating from Notch1-deleted pro-T cells. Chimeric mice lacking the
      Notch ligand delta-like 4 (Dll4) in thymus epithelium revealed an essential role
      for Dll4 in T cell development. Thus, Notch1-Dll4 signaling fortifies T cell
      commitment by suppressing non-T cell lineage potential in pro-T cells, and normal
      Notch1-driven T cell development repels excessive B cells in the thymus.

PMID- 19110449
TI  - The novel hormone INSL3 is expressed in human testicular Leydig cell tumors: a
      clinical and immunohistochemical study.
AB  - Insulin-like 3 (INSL3) is a novel peptidic hormone member of the relaxin-insulin
      like family of peptide factors. It is almost exclusively produced by Leydig cells
      within the testis and participates to the complex mechanisms leading to
      physiological testicular descent during embryonic development. We performed a
      retrospective study evaluating clinical and histopathological characteristics of
      13 patients surgically treated for testicular tumor and diagnosed to be affected
      by Leydig cell tumor (LCT). Furthermore, it was possible to retrieve the archived
      paraffin embedded tumor together with neighboring healthy testicular tissue of
      all subjects affected by LCT (12 benign and 1 malignant form), that were analyzed
      for INSL-3 expression. Immunohistochemical analysis of the tumor sections of the
      13 patients affected by LCT demonstrated constitutive expression of INSL3 protein
      in all LCT, irrespective of the histological pattern of each LCT and with no
      significant differences of staining intensity between all tumors. In particular,
      no gross differences were evident between the staining for INSL3 in the 12 benign
      LCTs and the only one showing malignant clinical behavior. The present study
      shows that LCTs, a very rare form of testicular tumor with no proven specific
      serum and histological markers, express a novel member of the relaxin-insulin
      like family of peptide factors previously identified as a secretory product of
      Leydig cells and named INSL3. Thus, there could be the possibility to evaluate
      the expression and secretion of this novel hormone as a marker of this rare
      testicular tumor.

PMID- 19110450
TI  - Is residual neurovascular tissue on prostatectomy specimens associated with
      surgeon intent at nerve-sparing and postoperative quality of life measures?
AB  - OBJECTIVES: Preservation of periprostatic neurovascular tissue at the time of
      radical prostatectomy has been correlated with subsequent erectile function and
      urinary continence. We evaluated whether the amount of neurovascular tissue
      identified on prostatectomy specimens correlated with surgeon's intention of
      nerve-sparing and/or predicted quality of life outcomes. MATERIALS AND METHODS:
      Radical prostatectomy specimens from 60 patients were evaluated by 2 pathologists
      for residual neurovascular bundle tissue. Reviewable pathology was available for
      17, 19, and 19 patients with bilateral, unilateral, and non-nerve-sparing radical
      prostatectomy, respectively. The patients completed the Expanded Prostate Cancer
      Index Composite, a validated quality of life questionnaire. Differences between
      neurovascular tissue thickness, surgeon's intent at nerve-sparing, and quality of
      life among patients in each group were analyzed using standard statistical
      software. RESULTS: Neurovascular tissue thickness identified on radical
      prostatectomy specimens did not correlate with surgeon's intent at performing a
      nerve-sparing procedure, nor was it found to be predictive of postoperative
      quality of life. Surgeon's intent at neurovascular preservation, however, was
      associated with improved sexual and urinary function scores at 1 year (both P <
      0.05). CONCLUSIONS: Surgeon intent, regardless of the amount of neurovascular
      tissue identified on radical prostatectomy specimen, is predictive of
      postoperative sexual-related and urinary quality of life. This suggests that
      factors other than the amount of neurovascular tissue spared contribute to
      postoperative sexual and urinary function.

PMID- 19110451
TI  - Kinetics of serum total and free prostate-specific antigen (PSA) after extended
      multisite prostate biopsy: Comparison among biopsy, transurethral resection of
      the prostate (TURP), and biopsy plus TURP.
AB  - BACKGROUND: The kinetics and reproducibility of serum prostate-specific antigen
      (PSA) following extended multisite biopsies are unknown. The aim of this study
      was to examine the kinetics of hematogenous leakage of PSA molecules by comparing
      the postintervention PSA manner among extended biopsies, transurethral resection
      of the prostate (TURP) and biopsy plus TURP. METHODS: Total and free PSA values
      were examined before and sequentially after intervention (at 1 hour, 24 hours, 2
      days, 14 days, and 28 days), in patients who underwent 14-core prostate biopsy
      (Biopsy, n = 53), TURP (TURP, n = 21), or prostate biopsy plus TURP (Biopsy+TURP,
      n = 18). RESULTS: Ten patients in the Biopsy group were histologically diagnosed
      as having prostate cancer, and all other patients were diagnosed with non
      malignant disorders. One hour after intervention, the increase in total PSA in
      the Biopsy group (mean 19.58 +/- 24.78-fold) and Biopsy+TURP group (mean 14.00 +/
      10.52-fold) was higher than that of the TURP group (mean 6.189 +/- 7.567-fold)
      (P = 0.0207 and 0.0119, respectively). The increase in total PSA in the
      Biopsy+TURP group was not different from that of the Biopsy group. The increase
      in free PSA in the Biopsy group (mean 36.52 +/- 21.18-fold or more) was greater
      than that of the TURP group (mean 15.57 +/- 18.17-fold) (P = 0.0002 or less).
      Both total and free PSA values in the Biopsy group recovered to the initial
      levels 28 days after intervention (P = 0.380 and P = 0.0873, respectively). The
      course of both total and free PSA values in the Biopsy group was not different
      between prostate cancer and non-malignant disorders. CONCLUSIONS: Extended
      multisite biopsies caused marked elevation of both total and free PSA compared
      with ordinary sextant protocol or TURP, and they reduced to the preoperative
      levels in about 4 weeks. The postintervention increase of PSA and its manner of
      recovery were comparable between the Biopsy and Biopsy+TURP groups, suggesting
      that the hematogenous leakage of PSA by biopsies occurs in an early phase just
      after biopsy and rapidly reduces also in the early phase.

PMID- 19110452
TI  - Immunohistochemical basis for adjuvant anti-angiogenic targeted therapy for renal
      carcinoid: initial case report.
AB  - OBJECTIVES: To evaluate the immunohistochemical profile of a carcinoid (low grade
      neuroendocrine tumor of the kidney) from a patient with lymph node positive
      disease who remains disease free for 31 months after radical nephrectomy, lymph
      node dissection, and adjuvant therapy with sunitinib malate. METHODS:
      Immunohistochemical staining was performed for chromogranin, synaptophysin, CD31,
      VEGF, HIF-1alpha, HIF-2, and Glut-1. Staining was evaluated in 3 high-power
      fields and samples scored as strongly positive (3+), moderately positive (2+),
      weakly positive (1+), or negative (0). A clear cell renal cell carcinoma was used
      as positive control. RESULTS: Immunohistochemical staining was strongly positive
      VEGF, weak to moderately positive for HIF-2, and negative for HIF-1alpha and Glut
      1. CONCLUSIONS: Our case of primary renal carcinoid stained intensely for VEGF
      and HIF-2, consistent with a VHL-HIF1-HIF2-Glut1 independent pathway for VEGF
      activation. These data suggest that like other neuroendocrine tumors, primary
      renal carcinoid is a potential target for anti-angiogenic therapy with sunitinib.

PMID- 19110453
TI  - Opium consumption and risk of bladder cancer: A case-control analysis.
AB  - OBJECTIVE: We evaluated the relationship between opium consumption and bladder
      cancer (BC) in a case-control study of an Iranian population. MATERIALS AND
      METHODS: In a hospital-based case-control study of 179 patients with BC and 179
      cancer-free controls frequency-matched by age, sex, and smoking status, we
      investigated the relationship between opium consumption and BC. A comprehensive
      epidemiologic interview was conducted on all participants to collect personal
      information, such as demographics and smoking status. RESULTS: Overall, we found
      significant age, sex, cigarette smoking adjusted association between BC risk and
      opium consumption, [odds ratio (OR) = 4.60; 95% confidence interval (CI) = 3.53
      6.28]. The elevated risk was more evident in older individuals (OR = 5.42; 95%
      CI, 4.12-7.28) than younger individuals (OR = 3.65; 95% CI, 2.76-4.76) (P =
      0.01). Heavy smokers with the opium consumption exhibited a 6-fold elevated risk
      for BC (OR = 6.16; 95% CI, 3.34-8.32) (P = 0.0001). When stratified according to
      different grades of BC, a 3.4-fold increased risk was associated with the opium
      consumption in grade III with an OR of 3.44 (95% CI, 2.82-8.28) (P = 0.001). A
      similar but slightly higher risk was also seen in case of grade IV tumors (OR =
      3.86; 95% CI, 2.14-10.16) (P = 0.001). Invasive bladder tumors were more common
      among the opiates users (OR = 2.6; 95% CI, 1.44-5.42) (P = 0.01). Cumulative risk
      of BC in women with opium consumption (OR = 4.10 95% CI, 3.54-5.88) (P = 0.001)
      was slightly less than in men (OR = 5.10 95% CI, 3.54-5.88) (P = 0.0001). Based
      on Pearson correlations, the risk of BC significantly correlated with opium
      dependence duration (r = 0.74, P = 0.001), type of opiate used (r = 0.65, P =
      0.001), and simultaneous cigarette smoking (r = 0.74, P = 0.0001). CONCLUSION:
      The results indicated that there is about 5-fold increase in risk of developing
      this cancer in the presence of opium consumption. Further research is needed to
      investigate the functional implications of the opium consumption in BC.

PMID- 19110454
TI  - Methotrexate, paclitaxel, ifosfamide, and cisplatin in poor-risk nonseminomatous
      germ cell tumors.
AB  - OBJECTIVE: The efficacy and tolerability of M-TIP was evaluated as first-line
      treatment for patients with poor-risk germ cell tumors (GCT), according to
      International Germ Cell Cancer Collaborative Group (IGCCCG) criteria. PATIENTS
      AND METHODS: Thirty patients with poor-risk GCT were treated with M-TIP
      (methotrexate 250 mg/m(2) given as a 4-hour infusion with folinic acid rescue on
      day 1, paclitaxel 175 mg/m(2) given as a 3-hour infusion on day 1, followed by
      ifosfamide 1.2 g/m(2) given as a 2-hour infusion and cisplatin 20 mg/m(2) given
      as a 2-hour infusion on days 2 to 6) regimen for four cycles. RESULTS: Five
      (16.6%, 95% confidence interval [CI]: 2%-31%) patients achieved clinical complete
      response (cCR) with chemotherapy only, 15 (50%, 95% CI: 31-69%) patients
      pathologic complete response (pCR) (11 had necrosis/fibrosis and 4 had mature
      teratoma) and 3 (10%) patients surgical complete response (sCR) for an overall
      favorable response of 76.6%. Twenty-one patients are continuously disease-free at
      a median follow-up of 5.3 years (range 0.9-8.4+ years), resulting in a 5-year
      progression-free survival (PFS) rate of 66.6% (95% CI = 49%-85%) and a 5-year
      survival rate of 70% (95% CI = 53%-87%). Toxicity was generally mild except for
      myelotoxicity. Patients with febrile neutropenia were successfully treated with
      broad spectrum antibiotics and G-CSF support. Hematologic toxicity in this trial
      was ameliorated with the use of G-CSF. Neurotoxicity and nephrotoxicity were not
      a problem, since only 6.6% and 3.3% of patients developed sensory neuropathy and
      renal toxicity, respectively. CONCLUSION: M-TIP is a highly effective (high
      proportion of patients achieved long-term disease-free status, lack of relapses)
      and well tolerated regimen for first-line treatment of poor-risk GCT patients.
      These results have to be compared with the standard BEP chemotherapy or more
      intensive regimens in multicentre randomized trials.

PMID- 19110456
TI  - Factors impacting on doctors' management of acute low back pain: a systematic
      review.
AB  - The aim of this review was to determine the factors that impact on doctors'
      management of patients with acute low back pain. A methodological assessment of
      databases (Medline, EMBASE, Psychinfo, BIOSIS, CINAHL, and the Cochrane Central
      Register of Controlled Trials) identified papers which were screened for
      inclusion criteria by two independent reviewers. Data were extracted from
      accepted papers, and the internal validity and strength of the evidence were
      determined using valid and reliable scales. The search generated a total of 28
      papers [quantitative (n=27), qualitative (n=1) methodologies]. Themes were
      identified from the accepted papers: education (n=18), knowledge of clinical
      guidelines and impact on management (n=7), and doctors' demographics (n=4). There
      was consistent evidence that doctors did not adhere to clinical guidelines when
      performing a spinal assessment. There was inconsistent evidence that education
      increased adherence with acute LBP guideline recommendations in terms of referral
      rates to physiotherapy, for investigations, to secondary care and for maintaining
      patients at work. Strategies to address the factors impacting on doctors'
      management of acute LBP are required; these would lead to improvement in patient
      outcomes and reduce healthcare costs.

PMID- 19110455
TI  - Cognitive complaints in a general population of older adults: prevalence,
      association with pain and the influence of concurrent affective disorders.
AB  - Previous studies examining the associations between pain and cognitive complaints
      have been in pain clinic outpatients; there has been no research in the general
      population setting. A cross-sectional postal survey of 7878 older adults, aged 50
      years and over, registered with three general practices (n=11230) in North
      Staffordshire using self-complete questionnaires was conducted. The questionnaire
      included the Alertness Behaviour Subscale from the Sickness Impact Profile to
      measure cognitive complaint, a full-body manikin to record presence and location
      of any recent pain (past 4 weeks) and the Hospital Anxiety and Depression Scale.
      The prevalence of any cognitive complaint was 46.5%; this increased with age
      (41.6% in 50-59 year olds to 63.4% in 80-100 year olds) and was higher in females
      than males (48.6% vs. 43.8%). Reporting recent pain was associated with a
      statistically significant increase in also reporting any cognitive complaint
      (odds ratio: 2.49; 95% confidence interval: 2.2, 2.8) and altered little after
      adjusting for age and gender. A dose-response relationship was seen when
      examining the association between pain and degree of cognitive complaint.
      Statistically significant associations between cognitive complaints and pain were
      seen across all anxiety and depression status. Cognitive complaints are common in
      a general population of older adults and are strongly related to the reporting of
      pain; a relationship which is independent of the presence of concurrent affective
      disorders. Taken together with previous work suggesting that subjective memory
      complaints are strongly correlated to risk of future cognitive decline, these
      results have implication for clinical practice in an aging population.

PMID- 19110457
TI  - Development of new indices to evaluate protein-protein interfaces: assembling
      space volume, assembling space distance, and global shape descriptor.
AB  - Protein-protein interaction is fundamental to initiate the cellular functions of
      proteins, and thus structural analyses of protein interfaces are the first step
      to understand their functions at the molecular level. Although shape
      complementarities have been used to evaluate the fitness of interfaces, the
      conventional method did not distinguish between two main components of
      complementarity, the well-fitting of the surface shapes and the size of the gap
      regions between the pair of molecules, and could not evaluate the global shape of
      the interfaces. Therefore, we now propose three new indices to describe protein
      interfaces: assembling space volume (ASV), assembling space distance (AS
      distance), and global shape descriptor (GS). The ASV is calculated using Delaunay
      tessellation, and the AS-distance is calculated as the ratio of ASV to delta-ASA
      (accessible surface area). The GS is calculated as the ratio of the volume of
      Delaunay tetrahedra with a long edge to that of all tetrahedra in the assembling
      space. To evaluate the feasibility of the three indices, we applied our method to
      homo-dimer proteins, and performed systematic comparisons with SURFNET by
      Laskowski and shape complementarity by Lawrence and Colman. As a result, our
      indices behave differently from the existing ones, and shed light on new features
      of protein-protein interfaces, as general trends of AS-distances for all protein
      interfaces.

PMID- 19110460
TI  - [For... systematic interrogation about para-aortic lymphadenectomy in endometrial
      carcinoma].

PMID- 19110458
TI  - Cotranscriptional recruitment of the mRNA export factor Yra1 by direct
      interaction with the 3' end processing factor Pcf11.
AB  - We investigated recruitment of the yeast mRNA export factor Yra1 to the
      transcription elongation complex (TEC). Previously, the Sub2 helicase subunit of
      TREX was proposed to recruit Yra1. We report that Sub2 is dispensable for Yra1
      recruitment, but the cleavage/polyadenylation factor, CF1A, is required. Yra1
      binds directly to the Zn finger/Clp1 region of Pcf11, the pol II CTD-binding
      subunit of CF1A, and this interaction is conserved between their human homologs.
      Tethering of Pcf11 to nascent mRNA is sufficient to enhance Yra1 recruitment.
      Interaction with Pcf11 can therefore explain Yra1 binding to the TEC
      independently of Sub2. We propose that after initially binding to Pcf11, Yra1 is
      transferred to Sub2. Consistent with this idea, Pcf11 binds the same regions of
      Yra1 that also contact Sub2, indicating a mutually exclusive interaction. These
      results suggest a mechanism for cotranscriptional assembly of the export
      competent mRNP and for coordinating export with 3' end processing.

PMID- 19110461
TI  - [How to prevent early postmenopausal fracture risk? Proposition of a strategy].
AB  - Postmenopausal osteoporosis is a chronic disease, which justifies long-term
      treatment in those women with an increased risk of fracture. The current
      disponibility of various drugs, which have demonstrated their efficacy in
      reducing the incidence of fracture, has raised the question of the best treatment
      strategy in a woman who would begin her postmenopausal period with an increased
      risk for fracture. Indeed, for most treatments (with the exception of hormonal
      replacement therapy [HRT]), their efficacy in reducing the risk of fracture has
      been mainly demonstrated in higher risk elderly women (above 65 years) with
      prevalent vertebral fractures. There is uncertainty concerning their cost
      effectiveness in younger women for a true primary prevention of the risk of
      fracture. Furthermore, current guidelines recommend a 5-year period of treatment
      which has led us to considering treatment strategies which would be based on
      various sequential treatment periods over time, the selection of each specific
      sequence being determined by the clinical situation of the woman, the level of
      her fracture risk and the expected skeletal (in terms of spectrum of bone
      effects) and potential extraskeletal benefits of drugs. In this regard, HRT or
      raloxifene, which allows a more global approach of the menopause-induced
      consequences of estrogen deficiency than the sole prevention of osteoporosis,
      should be privileged within the first 10 years of treatment or so in those
      youngest women at increased risk for subsequent fracture. Use of bisphosphonate
      or strontium ranelate should be thus reserved at a more advanced age, when the
      prevention of hip fracture becomes mandatory.

PMID- 19110459
TI  - Subunit compositions of the RNA-silencing enzymes Pol IV and Pol V reveal their
      origins as specialized forms of RNA polymerase II.
AB  - In addition to RNA polymerases I, II, and III, the essential RNA polymerases
      present in all eukaryotes, plants have two additional nuclear RNA polymerases,
      abbreviated as Pol IV and Pol V, that play nonredundant roles in siRNA-directed
      DNA methylation and gene silencing. We show that Arabidopsis Pol IV and Pol V are
      composed of subunits that are paralogous or identical to the 12 subunits of Pol
      II. Four subunits of Pol IV are distinct from their Pol II paralogs, six subunits
      of Pol V are distinct from their Pol II paralogs, and four subunits differ
      between Pol IV and Pol V. Importantly, the subunit differences occur in key
      positions relative to the template entry and RNA exit paths. Our findings support
      the hypothesis that Pol IV and Pol V are Pol II-like enzymes that evolved
      specialized roles in the production of noncoding transcripts for RNA silencing
      and genome defense.

PMID- 19110462
TI  - Optimization of ultrasonic-assisted extraction (UAE) of betulin from white birch
      bark using response surface methodology.
AB  - Betulin is an abundant naturally occurring triterpene, which makes it a
      potentially important raw material for a precursor of biologically active
      compounds. The objective of the current study was to determine the optimum UAE
      conditions for betulin from B. papyfera bark. The optimum conditions were
      evaluated with fractional factorial design and optimized using response surface
      methodology. High yields of betulin were observed from white birch bark by UAE
      technology. The solvent concentration and the ratio of material to solvent were
      the most significant parameters on betulin extraction as evaluated through FFD.
      The extraction conditions were further investigated with central composite
      design. The fitted second-order model revealed that the optimal conditions
      consisted of 98% ethonal concentration, 1:42 the ratio of white birch bark to
      solvent, extraction temperature 50 degrees C, ultrasonic frequency 5kHz and
      extraction time 3h. Under the optimized condition, the maximum productivity of
      betulin predicted is 23.17%. The extraction productivity and purity of betulin
      under the optimized extraction conditions were great higher than that of the non
      optimized condition. The present study demonstrates that ultrasound is a great
      efficiency tool for the fast extraction of betulin from white birch bark.

PMID- 19110463
TI  - Automatic detection method of muscle fiber movement as revealed by ultrasound
      images.
AB  - The objective of this study was to develop a method of muscle structure
      measurement based on the automatic analysis of muscle fibers, proximal fascias,
      and distal aponeurosis movements as revealed by a time-series of ultrasound
      images. This method was designed to detect changes in the length of muscle fiber
      movements, and its validity was demonstrated in a time-series of muscle movement,
      slow ankle dorsiflexion (10 degrees/s), by comparison to manual measurement. The
      results showed that, when this method was used, the changes in the length of the
      muscle fiber under slow muscle movement were smaller than those in manual
      operations by novice individuals. However, with the proposed method, it was
      possible to obtain a sufficient degree of validity and reliability for the
      changes in the length of the muscle fiber length compared with those in manual
      operations, since the correlation coefficients exceeded 0.8 which was tested by
      the linear regression. The proposed method suggests that automation reduces the
      errors caused by manual operations and makes the processing of data possible in
      an acceptable amount of time.

PMID- 19110464
TI  - Infrared and Raman spectra of triacetoxyvinylsilane, aqueous sol-gel and xerogel.
AB  - Triacetoxyvinylsilane (TAVS) has been used as a precursor to prepare sol-gel
      under aqueous conditions. The sol-gel product has been applied for the surface
      treatment of aluminum. Infrared and Raman spectra have been collected for TAVS
      and for TAVS sol-gel, xerogel and sol-gel-coated aluminum. Vibrational analyses
      have been suggested for the recorded spectra based essentially on the group
      frequencies and the spectral variation with the change of the sol-gel product
      states and the vibrational assignments of similar molecules. From the recorded
      infrared and Raman spectra of the sol-gel and xerogel, it is found that the sol
      gel produced in the process with TAVS is essentially the same as that prepared
      from vinyltriethoxysilane. Thermo-gravimetric analysis (TGA) of TAVS xerogel has
      been conducted, and an explanation has been given in coordination with the
      results obtained from IR spectroscopic study of the xerogels cured at different
      temperatures. The study has demonstrated the thermal effect on the condensation
      of the sol-gel process and on the vinyl decomposition of TAVS xerogel.

PMID- 19110465
TI  - Composites containing confined n-octyl-cyanobiphenyl: monomer and dimer species
      in the surface layer by in situ FTIR spectroscopy.
AB  - Confinement of 4-n-octyl-4'-cyanobiphenyl (8CB) to nanoporous molecular sieves
      with hexagonal structure of cylindrical pores (4.6nm diameter) is studied.
      Thermogravimetric investigations have indicated that the pores are completely
      filled. Several surface species inside the pores and onto the external surface of
      the grains were demonstrated by differential thermal analysis and by in situ
      infrared spectroscopy. Arguments are given that bulk-like monomer and dimer
      species along with hydrogen bonded ones might coexist in the so-called surface
      layer, but their population varies drastically as function of the temperature. In
      addition, chemical changes of the confined liquid crystal are quite possible
      inside these nanopores, at temperatures lower than for the bulk.

PMID- 19110466
TI  - Laboratory evaluation of the UniCel DxI 800 analyser (Beckman Coulter) for
      detecting HBV and HCV serological markers.
AB  - BACKGROUND: Due to their high prevalence, hepatitis B virus (HBV) and hepatitis C
      virus (HCV) infections need accurate and rapid diagnosis tools. OBJECTIVES:
      Technical performances of the UniCel DxI 800 analyser (Beckman Coulter) and a
      comparison with the Vitros ECi (Ortho Clinical Diagnostics) were performed for
      five serological markers: HBsAg, total anti-HBc, anti-HBc IgM, anti-HBs and anti
      HCV. STUDY DESIGN: Reproducibility was determined by repeated tests on the
      manufacturers' controls. The performance of the UniCel DxI 800 was assessed by
      testing negative and positive samples previously analysed with the Vitros ECi.
      The accuracy and linearity of anti-HBs assay were evaluated using the WHO
      international standard (W1042). RESULTS: The intra-assay and inter-assay
      coefficients of variation were: 0.8% and 4.4% for HBsAg, 2.4% and 6.2% for anti
      HBc, 5% and 8.7% for anti-HBc IgM, 2.1% and 5.1% for anti-HBs and 3.7% and 7.4%
      for anti-HCV. The two methods were concordant: 100% agreement for the five
      markers except for the negative HBsAg sera (99%). The anti-HBs results correlated
      well with the Vitros ECi (r=0.925 with p<0.0001) and the WHO standard
      (r2=0.9996). Throughput was 216 tests/h. CONCLUSION: The high throughput,
      specificity and sensitivity make UniCel DxI 800 assays useful for routine
      diagnoses of HCV and HBV infections.

PMID- 19110467
TI  - All-night EEG power spectral analysis of the cyclic alternating pattern at
      different ages.
AB  - OBJECTIVE: To analyze in detail the frequency content of the different EEG
      components of the Cyclic Alternating Pattern (CAP) in the whole sleep of pre
      school and school age children compared to normal young adults. METHODS: Fourteen
      pre-school age and 18 school age children and 16 adults were included in this
      study. Each participant underwent a polysomnographic overnight recording, after
      an adaptation night; sleep stages and CAP were scored following standard
      criteria. Average spectra were obtained for each CAP condition from the signal
      recorded from C3/A2 or C4/A1, separately in sleep stage 2 and slow-wave sleep
      (SWS), for each subject. RESULTS: The analysis of the relative power density in
      the three groups showed that in sleep stage 2 and in SWS, CAP A1, A2, A3 subtypes
      had a significantly higher power in all frequency ranges in pre-school children
      than in adults, while school children differed mainly for the lower frequencies
      (<7 Hz). For non-CAP, pre-school and school children differed from adults at
      almost all frequencies analyzed. Generally, A1, A2 and A3 showed clear spectral
      differences in the three different groups of subjects with pre-school age
      children showing slightly less evident differences. CONCLUSIONS: CAP subtypes are
      characterized by clearly different spectra at different ages and also the same
      subtype shows a different power spectrum, during sleep stage 2 or SWS. This study
      shows that pre-school children have a different structure of sleep, especially
      from the microstructural (CAP) point of view: the differences are evident for all
      the CAP components and for non-CAP in almost all the frequency bands. This
      finding might be associated to the age-related delta decline in the 0-3 Hz
      frequency reported in children of the same age. SIGNIFICANCE: Our data seem to
      provide information not available before and useful for the understanding of the
      impact of CAP on the sleep EEG neurophysiological dynamics at different ages.
      This type of information is crucial for a more adequate interpretation of data
      provided by a growing number of studies analyzing CAP in groups of pediatric
      patients.

PMID- 19110468
TI  - Ethnic differences regarding sensory, pain, and reflex responses in the
      trigeminal region.
AB  - OBJECTIVE: The present study evaluated ethnic differences in sensory, pain
      responses, and the exteroceptive suppression reflex (ES) in the trigeminal
      region. METHODS: Twenty-eight Caucasian (14 men and 14 women, age from 20 to 31)
      and 28 gender and age matched Japanese participated. Tactile detection thresholds
      and filament-prick pain detection thresholds were measured on the left cheek
      skin. Surface EMG was recorded from the left masseter muscle, and 13 different
      intensities of electrical stimuli were applied to the skin overlying the left
      mental nerve. The first stimulation intensity at which the late ES appeared was
      defined as the electrical reflex threshold. The duration and suppression degree
      of the ES were also determined. RESULTS: Japanese subjects had a significantly
      lower sensory and pain threshold then Caucasian subjects. Caucasian subjects had
      a significantly lower electrical reflex threshold in comparison to Japanese
      subjects. Caucasian subjects had significantly longer duration of the ES and
      larger suppression degree of the ES compared to Japanese subjects. CONCLUSIONS:
      Our results demonstrate that ethnic differences exist not only concerning sensory
      and pain responses but also regarding reflex (motor) responses. SIGNIFICANCE: The
      findings of this study have direct implications for studies evaluating different
      types of orofacial pain conditions and trigeminal reflexes.

PMID- 19110469
TI  - Predictors of restless legs syndrome in pregnancy: a hospital based cross
      sectional survey from Pakistan.
AB  - Restless legs syndrome (RLS) is more common in pregnant women. The objective of
      our study was to determine frequency of RLS in pregnant women and predictors of
      RLS in pregnancy in Pakistan. All pregnant women admitted at The Aga Khan
      University Hospital for delivery from June to July 2005 were enrolled. Eighty-one
      of 271 (30%) interviewed women fulfilled the diagnostic criteria of RLS. One
      hundred seventeen (43%) of the subjects dropped their haemoglobin during the
      pregnancy. No significant difference in haemoglobin drop was noted between the
      RLS group and healthy group. On multivariate analysis family history of RLS (OR:
      8.43, CI: 2.32-30.57, p value<0.001), history of RLS in prior pregnancy (OR:
      53.74, CI: 6.72-429.8, p value<0. 001), history of RLS in past even when non
      pregnant (OR: 12.91, CI: 3.34-49.87, p value<0.001) and haemoglobin of 11g/dL or
      less (OR: 2.05, CI: 1.04-4.04, p value 0.036) were found to be independent
      predictors of RLS during pregnancy. Subgroup analysis revealed that family
      history of RLS (OR: 3.06, CI: 1.2-7.83, p value 0.019) and anemia (OR: 1.89, CI:
      0.96-3.71, p value 0.06) were associated with de novo RLS, and family history of
      RLS (OR: 12.39, CI: 4.45-35.54, p value<0.001) and multiparity (OR: 6.84, CI:
      2.15-21.71, p value 0.001) were predictors of pre-existing RLS.

PMID- 19110470
TI  - Evaluation of integrated vector management.
AB  - Initiatives on integrated vector management (IVM) approaches are increasingly
      undertaken as alternatives to existing vector control. An impact model of IVM is
      presented with performance and impact indicators at six causal steps from
      coverage of the intervention to impact on disease. Impacts in fields other than
      health are also discussed because of the emphasis in IVM on capacity building,
      partnerships and sustainability. A conceptual framework for evaluation of IVM is
      designed, based on considerations of the selection of indicators, level of
      inference, cluster size and method of evaluation. The framework, which is tested
      in three case studies, is intended as guidance for public health workers and
      policy-makers.

PMID- 19110472
TI  - Blood transfusion in Canada: the early years.
AB  - In the early 20th Century most of the development of blood transfusion occurred
      in the United States. Transfusion activity in Canada dates from 1910, with
      evidence of its systematic use in both Toronto and Montreal prior to the First
      World War. Its use was quickly and widely accepted and exploited, particularly
      under the pressure of support for the management of war injuries. Within a decade
      transfusion was being used in the practice of surgery, pediatrics, internal
      medicine and obstetrics, both in University associated hospitals and in community
      and domiciliary practice, and indications for use developed.

PMID- 19110471
TI  - Evolution of foamy macrophages in the pulmonary granulomas of experimental
      tuberculosis models.
AB  - The chronic phase of Mycobacterium tuberculosis infection in mouse experimental
      models is characterized by the accumulation of foamy macrophages (FM)--which
      shape the outer ring of the granuloma - in the alveolar spaces, as detected in
      paraffin-embedded tissues stained with hematoxylin-eosin. In this study, the use
      of semi- and ultra-thin sections offers more detailed information about the
      origin of FM both in mouse and guinea-pig experimental models. Lipid bodies (LB)
      are present in macrophages from the beginning of infection and accumulate in the
      chronic phase. LB progress from an early (ELB) to a late (LLB) stage, defined
      according to their progressive capacity to generate cholesterol crystals,
      resembling atherosclerotic lesions. FM arise from massive accumulation of LLB.
      Electronic microscopy reveals intracellular lipophilic inclusions (ILIs) in those
      M. tuberculosis bacilli inside FM. It is our hypothesis that the accumulation of
      lipids in M. tuberculosis concomitant to the establishment of the non-replicating
      state prepares the bacilli for future reactivation and for facing future
      stressful environments.

PMID- 19110473
TI  - Are oestrogens useful for the treatment of depression in women?
AB  - The relationship between mood changes and the menstrual cycle has been recognized
      for many years. Initial treatments involved removal of the ovaries to prevent
      fluctuation of oestradiol, but this was also associated with the long-term
      effects of hypo-oestrogenism such as osteoporosis or heart disease. More
      recently, the use of high-dose oestrogen has been explored with some success. A
      diagnosis of hormone-related depression is made on the history, where the problem
      is worse at a time of hormone fluctuation such as occurs in the premenstrual
      phase, in the postnatal period and in the years leading up to the menopause. Many
      women may only feel well for a minority of days in the month and the problem can
      become chronic. Antidepressant medication is not usually successful, although
      this is often the preferred treatment for general practitioners and
      psychiatrists, possibly because of the potential side-effects of high-dose
      oestrogen administration. This chapter covers the diagnosis and treatment of
      premenstrual depression, postnatal depression and depression occurring in the
      climacteric period to emphasize the chronic nature of the problem and the best
      ways of diagnosing and relieving this distressing condition.

PMID- 19110474
TI  - Lidocaine transport through a cellophane membrane by alternating current
      iontophoresis with a duty cycle.
AB  - The purpose of this study was to determine whether lidocaine can be efficiently
      transported across a cellophane membrane using a square-wave alternating current
      (AC) with an adjusted duty cycle. Three voltages at 1 kHz with 6 duty cycles were
      applied for 60 min to the diffusion cells on both sides of the cellophane
      membrane. The donor chamber was filled with 1% lidocaine hydrochloride solution.
      The transport of lidocaine was enhanced in a voltage-, and duty cycle-dependent
      manner. These findings indicate that voltage and the direct current (DC)
      component of the square-wave AC play important roles in generating the driving
      force necessary for lidocaine delivery. Additionally, the periodic polarity
      alteration could reduce the electrode polarization. The higher voltages and duty
      cycles induced a pH change. The practical electrical conditions which are
      preferable for clinical application were 10 V with a 70% duty cycle or 20 V with
      a 60% duty cycle.

PMID- 19110475
TI  - Quantitative high-performance liquid chromatography analysis of the pool levels
      of undecaprenyl phosphate and its derivatives in bacterial membranes.
AB  - Undecaprenyl phosphate is the essential lipid involved in the transport of
      hydrophilic motifs across the bacterial membranes during the synthesis of cell
      wall polymers such as peptidoglycan. A HPLC procedure was developed for the
      quantification of undecaprenyl phosphate and its two derivatives, undecaprenyl
      pyrophosphate and undecaprenol. During the exponential growth phase, the pools of
      undecaprenyl phosphate and undecaprenyl pyrophosphate were ca. 75 and 270 nmol/g
      of cell dry weight, respectively, in Escherichia coli, and ca. 50 and 150 nmol/g,
      respectively, in Staphylococcus aureus. Undecaprenol was detected in S. aureus
      (70 nmol/g), but not in E. coli (<1 nmol/g).

PMID- 19110476
TI  - Development and validation of a liquid chromatography-atmospheric pressure
      photoionization-mass spectrometry method for the quantification of alprazolam,
      flunitrazepam, and their main metabolites in haemolysed blood.
AB  - A LC-APPI-MS method was developed and validated for the detection of alprazolam,
      flunitrazepam and their major metabolites in haemolysed blood. Samples were
      diluted with water (2:1, v:v) and extracted with a hydrophobic-lipophilic
      balanced copolymer. The method was fully validated according to ICH guidelines
      and SFSTP protocols. Deuterated internal standards of both parent drugs were used
      and good quantitative performance was achieved in terms of trueness and precision
      (repeatability and intermediate precision) since accuracy profiles were achieved
      within the acceptance limits (+/-30% for biological samples). The LC-APPI-MS
      method was linear over the concentration range of 1-1000 and 3-1000 ng/mL, for
      alprazolam and flunitrazepam, respectively. Lower limits of quantification as low
      as 1 ng/mL in haemolysed blood were reached and the method was successfully
      applied to the quantification of alprazolam, flunitrazepam and their major
      metabolites in real toxicological samples.

PMID- 19110477
TI  - Validated LC-MS/MS method for determination of Alverine and one of its hydroxy
      metabolites in human plasma along with its application to a bioequivalence study.
AB  - The present research work involves a first of its kind rapid and sensitive liquid
      chromatography-tandem mass spectrometry (LC-MS/MS) method developed and validated
      for simultaneous analysis of Alverine (ALV) and one of its hydroxy metabolites,
      para hydroxy Alverine (PHA) in human plasma. The analytes were extracted from the
      matrix using a simple solid-phase extraction procedure. Mebeverine was used as
      the internal standard for both analytes. A Kromasil C8 column provided
      chromatographic separation of analytes followed by detection with mass
      spectrometry. The method involves simple isocratic chromatography conditions and
      mass spectrometric detection in the positive ionization mode using an API 5000
      MS/MS system. The proposed method has been validated with a linear range of 100
      10,000 pg/mL for both ALV and PHA. The interrun and intrarun precision values are
      within 6.3%, 3.7% for ALV and 6.3%, 3.2% for PHA at LOQ levels. The intrarun
      accuracy in terms of % RE was within the range of -7.0% to -0.1% and -8.1% to 
      1.7% for ALV and PHA, respectively whereas the interrun accuracy was within the
      range of -5.1% to -0.5% for ALV and -8.6% to 0.4% for PHA, respectively. The
      overall recoveries for ALV and PHA were 83.5% and 86.2% respectively. Total
      elution time was about 4 min which allowed quantitation of more than 150 plasma
      samples per day. This validated method was used successfully for analysis of real
      samples from a bioequivalence study.

PMID- 19110478
TI  - Implementation of ERAS and how to overcome the barriers.
AB  - BACKGROUND: Multimodal care or Enhanced Recovery after Surgery (ERAS) protocols
      are gaining popularity in order to modify surgical stress responses after colonic
      resection. However, these protocols are not straightforward to implement as peri
      operative care is varied. We aimed to identify areas that may need attention in
      order to successfully change practice. METHOD: The literature was reviewed for
      current practice, methods and issues in implementing ERAS. Based on this and our
      own experience we discuss several important areas that need particular attention
      in developing and sustaining an ERAS program. RESULTS: International surveys have
      shown that current peri-operative care in colorectal resection is not evidence
      based. Important aspects of the ERAS philosophy including patient counselling,
      teamwork and attitude change are identified and discussed. CONCLUSION:
      Implementing evidence-based peri-operative care into practice is challenging.
      Barriers to multimodal recovery pathways should be addressed.

PMID- 19110479
TI  - Immediate breast reconstruction in the elderly: can it be considered an integral
      step of breast cancer treatment? The experience of the European Institute of
      Oncology, Milan.
AB  - BACKGROUND: In the last few decades, breast reconstruction often has not been
      offered to the elderly population due to the reluctance of clinicians concerned
      about serious co-morbidities. This study aims to demonstrate that breast
      reconstruction is feasible and safe in the elderly cohort. METHODS: Between 1999
      and 2004, 63 elderly patients underwent an immediate reconstruction after breast
      cancer treatment at the European Institute of Oncology. A conservative treatment,
      combined with breast repair by plastic surgical techniques, was performed in 14
      patients. In the remaining 49 patients, a modified radical mastectomy was
      necessary in 30 breasts, a total mastectomy in 19, a subcutaneous mastectomy in
      one case and a radical mastectomy in one patient. Three nipple-sparing
      mastectomies, along with intra-operative radiotherapy, were performed in two
      patients. A definitive silicone implant was used in 41 breasts and a skin
      expander in eight cases. A latissimus dorsi flap was performed in two patients, a
      pedicled transverse rectus abdominis muscle (TRAM) flap in two cases and a local
      advancement fasciocutaneous flap in another two patients. RESULTS: In all
      patients, surgery was well tolerated despite patient age. No systemic and
      medically unfavourable events occurred in the immediate and late postoperative
      period. Infection occurred in four patients (6.34%) and partial necrosis of the
      mastectomy flaps in three cases (5.5% of the mastectomies). Capsular contracture
      grade III and IV was reported in four cases (8.89%). Total implant removal was
      rated 12.24%, due to infection (three prostheses), exposure (one expander) and
      capsular contracture grade IV (two implants). CONCLUSIONS: Implant-based
      technique of breast reconstruction should be made available to the elderly
      population.

PMID- 19110481
TI  - Lipid binding to the tail domain of vinculin: specificity and the role of the N
      and C termini.
AB  - Vinculin is a highly conserved and abundant cytoskeletal protein involved in
      linking the actin cytoskeleton to the cell membrane at sites of cellular
      adhesion. At these sites of adhesion, vinculin plays a role in physiological
      processes such as cell motility, migration, development, and wound healing. Loss
      of normal vinculin function has been associated with cancer phenotypes,
      cardiovascular disease, and lethal errors in embryogenesis. The tail domain of
      vinculin (Vt) binds to acidic phospholipids and has been proposed to play a role
      in vinculin activation and focal adhesion turnover. To better characterize Vt
      lipid specificity, we conducted a series of lipid co-sedimentation experiments
      and find that Vt shows specific association with phosphatidylinositol 4,5
      bisphosphate (PIP2), compared with phosphatidylethanolamine (PE),
      phosphatidylcholine (PC), phosphatidylserine (PS), or phosphatidylinositol (PI)
      in the context of mixed lipid vesicles. The C terminus of Vt has been proposed to
      be important for PIP2 association, as various mutations and deletions within the
      C-terminal reduce PIP2 association. Lipid co-sedimentation and NMR analyses
      indicate that removal of the hydrophobic hairpin does not alter Vt structure or
      PIP2 association. However, more extensive deletions within the C-terminal
      introduce Vt structural perturbations and reduce PIP2 binding. Intriguingly, a
      significant increase in PIP2 binding was observed for multiple Vt variants that
      perturb interactions between the N-terminal strap and helix bundle, suggesting
      that a rearrangement of this N-terminal strap may be required for PIP2 binding.

PMID- 19110480
TI  - Peroxisome deficiency causes a complex phenotype because of hepatic SREBP/Insig
      dysregulation associated with endoplasmic reticulum stress.
AB  - Regulation of hepatic cholesterol biosynthesis, lipogenesis, and insulin
      signaling intersect at the transcriptional level by control of SREBP and Insig
      genes. We previously demonstrated that peroxisome-deficient PEX2-/- mice activate
      SREBP-2 pathways but are unable to maintain normal cholesterol homeostasis. In
      this study, we demonstrate that oral bile acid treatment normalized hepatic and
      plasma cholesterol levels and hepatic cholesterol synthesis in early postnatal
      PEX2 mutants, but SREBP-2 and its target gene expressions remained increased.
      SREBP-2 pathway induction was also observed in neonatal and longer surviving PEX2
      mutants, where hepatic cholesterol levels were normal. Abnormal expression
      patterns for SREBP-1c and Insig-2a, and novel regulation of Insig-2b, further
      demonstrate that peroxisome deficiency widely affects the regulation of related
      metabolic pathways. We have provided the first demonstration that peroxisome
      deficiency activates hepatic endoplasmic reticulum (ER) stress pathways,
      especially the integrated stress response mediated by PERK and ATF4 signaling.
      Our studies suggest a mechanism whereby ER stress leads to dysregulation of the
      endogenous sterol response mechanism and concordantly activates oxidative stress
      pathways. Several metabolic derangements in peroxisome-deficient PEX2-/- liver
      are likely to trigger ER stress, including perturbed flux of mevalonate
      metabolites, altered bile acid homeostasis, changes in fatty acid levels and
      composition, and oxidative stress.

PMID- 19110482
TI  - Localization of mesenchymal cells in adult mouse thymus: their abnormal
      distribution in mice with disorganization of thymic medullary epithelium.
AB  - Thymic mesenchymal cells are known to be important for the development of the
      early fetal thymus into a functionally mature organ supporting T cell
      differentiation. We examined the expression of mesenchymal markers: pan
      mesenchymal marker ER-TR7, desmin, alpha-smooth muscle actin (alpha-SMA), and
      alpha- and beta-chain of platelet-derived growth factor receptor (PDGFRalpha,
      PDGFRbeta) in thymi of normal adult mice. Desmin and ER-TR7 revealed specific
      staining in the capsule, septa, and perivascular cells. Most perivascular cells
      highly expressed PDGFRbeta at the same levels as desmin. Low expression of
      PDGFRalpha was detected in the capsule, intralobular septa, and some perivascular
      cells of normal adult thymi. alpha-SMA, used to identify vascular smooth muscle
      cells, was detectable on arterioles and some large venules but not on
      capillaries. Thus, desmin, PDGFRalpha, and PDGFRbeta were localized in the
      capsule, septa, and perivascular cells in thymus of adult mouse, although there
      were differences in the expression level among these markers. On the other hand,
      the expression of mesenchymal markers was detectable in the region of the thymic
      medullary epithelium of lymphotoxin beta receptor-deficient mice and plt/plt
      mice, indicating that mesenchymal cells were abnormally localized in the region.
      These results suggest that disorganization of the medullary epithelium may be
      accompanied by aberrant distribution of mesenchyme in adult mouse thymus.

PMID- 19110483
TI  - Expression of Muc19/Smgc gene products during murine sublingual gland
      development: cytodifferentiation and maturation of salivary mucous cells.
AB  - Muc19/Smgc expresses two splice variants, Smgc (submandibular gland protein C)
      and Muc19 (mucin 19), the latter a major exocrine product of differentiated
      murine sublingual mucous cells. Transcripts for Smgc were detected recently in
      neonatal sublingual glands, suggesting that SMGC proteins are expressed during
      initial salivary mucous cell cytodifferentiation. We therefore compared
      developmental expression of transcripts and translation products of Smgc and
      Muc19 in sublingual glands. We find abundant expression of SMGC within the
      initial terminal bulbs, with a subsequent decrease as Muc19 expression increases.
      During postnatal gland expansion, SMGC is found in presumptive newly formed
      acinar cells and then persists in putative acinar stem cells. Mucin levels
      increase 7-fold during the first 3 weeks of life, with little change in
      transcript levels, whereas between postnatal days 21 and 28, there is a 3-fold
      increase in Muc19 mRNA and heteronuclear RNA. Our collective results demonstrate
      the direct transition from SMGC to Muc19 expression during early mucous cell
      cytodifferentiation and further indicate developmentally regulated changes in
      Muc19/Smgc transcription, alternative splicing, and translation. These changes in
      Muc19/Smgc gene expression delineate multiple stages of salivary mucous cell
      cytodifferentiation and subsequent maturation during embryonic gland development
      through the first 4 weeks of postnatal life.

PMID- 19110484
TI  - Screening instruments for delirium in older people with an acute medical illness.

PMID- 19110485
TI  - Genetic risk factors in typical haemolytic uraemic syndrome.
AB  - BACKGROUND: Haemolytic uraemic syndrome (HUS) is a disorder characterized by
      thrombotic microangiopathy, which is caused in 'typical forms' by
      gastrointestinal infections with Escherichia Coli species that produce
      verotoxins. Several studies have identified negative prognostic factors of the
      disease, among which prolonged oliguria, neurological involvement and increased
      leukocytosis have been more consistently reported. We have hypothesized that the
      genetic background may also predispose to the development of typical forms of HUS
      and may influence the clinical course of the disease. METHODS: Fourteen
      polymorphisms, known to influence the coagulation pathway or the activity of the
      renin-angiotensin system, have been selected and studied in 150 Italian children
      with typical forms of HUS. Two hundred healthy Italian children were used as
      controls. RESULTS: The risk of developing HUS was strongly associated with the
      platelet glycoprotein 1balpha 145M allele (OR 3.08; CI: 1.62-5.85) (P < 0.001). A
      significant association was also found with polymorphisms located in the
      adipocyte-derived leucine aminopeptidase and factor V genes. A longer duration of
      dialysis was moderately associated with increased leukocytosis and with the 807T
      allele of the platelet glycoprotein 1a gene. High white blood cell count was also
      strongly associated with the risk of long-term sequelae (OR 2.91, CI: 1.21-6.98)
      (P < 0.02), whereas the 1166C allele of the angiotensin II type 1 receptor had a
      significant protective effect (OR 0.28, CI: 0.09-0.83) (P < 0.02). CONCLUSIONS:
      These results highlight the role of glycoprotein 1balpha in the physiopathology
      of typical forms of HUS and show that the genetic background plays a role in the
      susceptibility and severity of the disease.

PMID- 19110486
TI  - Stem cell therapy for Alport syndrome: the hope beyond the hype.

PMID- 19110487
TI  - Mystery of pentraxin-3 not yet resolved: still a long way to its prime time in
      surgery.

PMID- 19110488
TI  - Offline loop investigation for handwriting analysis.
AB  - Resolution of different types of loops in handwritten script presents a difficult
      task and is an important step in many classic word recognition systems, writer
      modeling, and signature verification. When processing a handwritten script, a
      great deal of ambiguity occurs when strokes overlap, merge, or intersect. This
      paper presents a novel loop modeling and contour-based handwriting analysis that
      improves loop investigation. We show excellent results on various loop resolution
      scenarios, including axial loop understanding and collapsed loop recovery. We
      demonstrate our approach for loop investigation on several realistic data sets of
      static binary images and compare with the ground truth of the genuine online
      signal.

PMID- 19110489
TI  - Robust face recognition via sparse representation.
AB  - We consider the problem of automatically recognizing human faces from frontal
      views with varying expression and illumination, as well as occlusion and
      disguise. We cast the recognition problem as one of classifying among multiple
      linear regression models and argue that new theory from sparse signal
      representation offers the key to addressing this problem. Based on a sparse
      representation computed by l{1}-minimization, we propose a general classification
      algorithm for (image-based) object recognition. This new framework provides new
      insights into two crucial issues in face recognition: feature extraction and
      robustness to occlusion. For feature extraction, we show that if sparsity in the
      recognition problem is properly harnessed, the choice of features is no longer
      critical. What is critical, however, is whether the number of features is
      sufficiently large and whether the sparse representation is correctly computed.
      Unconventional features such as downsampled images and random projections perform
      just as well as conventional features such as Eigenfaces and Laplacianfaces, as
      long as the dimension of the feature space surpasses certain threshold, predicted
      by the theory of sparse representation. This framework can handle errors due to
      occlusion and corruption uniformly by exploiting the fact that these errors are
      often sparse with respect to the standard (pixel) basis. The theory of sparse
      representation helps predict how much occlusion the recognition algorithm can
      handle and how to choose the training images to maximize robustness to occlusion.
      We conduct extensive experiments on publicly available databases to verify the
      efficacy of the proposed algorithm and corroborate the above claims.

PMID- 19110490
TI  - Natural image statistics and low-complexity feature selection.
AB  - Low-complexity feature selection is analyzed in the context of visual
      recognition. It is hypothesized that high-order dependences of bandpass features
      contain little information for discrimination of natural images. This hypothesis
      is characterized formally by the introduction of the concepts of conjunctive
      interference and decomposability order of a feature set. Necessary and sufficient
      conditions for the feasibility of low-complexity feature selection are then
      derived in terms of these concepts. It is shown that the intrinsic complexity of
      feature selection is determined by the decomposability order of the feature set
      and not its dimension. Feature selection algorithms are then derived for all
      levels of complexity and are shown to be approximated by existing information
      theoretic methods, which they consistently outperform. The new algorithms are
      also used to objectively test the hypothesis of low decomposability order through
      comparison of classification performance. It is shown that, for image
      classification, the gain of modeling feature dependencies has strongly
      diminishing returns: best results are obtained under the assumption of
      decomposability order 1. This suggests a generic law for bandpass features
      extracted from natural images: that the effect, on the dependence of any two
      features, of observing any other feature is constant across image classes.

PMID- 19110491
TI  - An analysis of ensemble pruning techniques based on ordered aggregation.
AB  - Several pruning strategies that can be used to reduce the size and increase the
      accuracy of bagging ensembles are analyzed. These heuristics select subsets of
      complementary classifiers that, when combined, can perform better than the whole
      ensemble. The pruning methods investigated are based on modifying the order of
      aggregation of classifiers in the ensemble. In the original bagging algorithm,
      the order of aggregation is left unspecified. When this order is random, the
      generalization error typically decreases as the number of classifiers in the
      ensemble increases. If an appropriate ordering for the aggregation process is
      devised, the generalization error reaches a minimum at intermediate numbers of
      classifiers. This minimum lies below the asymptotic error of bagging. Pruned
      ensembles are obtained by retaining a fraction of the classifiers in the ordered
      ensemble. The performance of these pruned ensembles is evaluated in several
      benchmark classification tasks under different training conditions. The results
      of this empirical investigation show that ordered aggregation can be used for the
      efficient generation of pruned ensembles that are competitive, in terms of
      performance and robustness of classification, with computationally more costly
      methods that directly select optimal or near-optimal subensembles.

PMID- 19110492
TI  - Geometric mean for subspace selection.
AB  - Subspace selection approaches are powerful tools in pattern classification and
      data visualization. One of the most important subspace approaches is the linear
      dimensionality reduction step in the Fisher's linear discriminant analysis
      (FLDA), which has been successfully employed in many fields such as biometrics,
      bioinformatics, and multimedia information management. However, the linear
      dimensionality reduction step in FLDA has a critical drawback: for a
      classification task with c classes, if the dimension of the projected subspace is
      strictly lower than c - 1, the projection to a subspace tends to merge those
      classes, which are close together in the original feature space. If separate
      classes are sampled from Gaussian distributions, all with identical covariance
      matrices, then the linear dimensionality reduction step in FLDA maximizes the
      mean value of the Kullback-Leibler (KL) divergences between different classes.
      Based on this viewpoint, the geometric mean for subspace selection is studied in
      this paper. Three criteria are analyzed: 1) maximization of the geometric mean of
      the KL divergences, 2) maximization of the geometric mean of the normalized KL
      divergences, and 3) the combination of 1 and 2. Preliminary experimental results
      based on synthetic data, UCI Machine Learning Repository, and handwriting digits
      show that the third criterion is a potential discriminative subspace selection
      method, which significantly reduces the class separation problem in comparing
      with the linear dimensionality reduction step in FLDA and its several
      representative extensions.

PMID- 19110493
TI  - Semisupervised learning of hidden Markov models via a homotopy method.
AB  - Hidden Markov model (HMM) classifier design is considered for the analysis of
      sequential data, incorporating both labeled and unlabeled data for training; the
      balance between the use of labeled and unlabeled data is controlled by an
      allocation parameter ?lambda ?in [0, 1), where ?lambda = 0 corresponds to purely
      supervised HMM learning (based only on the labeled data) and ?lambda = 1
      corresponds to unsupervised HMM-based clustering (based only on the unlabeled
      data). The associated estimation problem can typically be reduced to solving a
      set of fixed-point equations in the form of a "natural-parameter homotopy." This
      paper applies a homotopy method to track a continuous path of solutions, starting
      from a local supervised solution (?lambda = 0) to a local unsupervised solution
      (?lambda = 1). The homotopy method is guaranteed to track with probability one
      from ?lambda = 0 to ?lambda = 1 if the ?lambda = 0 solution is unique; this
      condition is not satisfied for the HMM since the maximum likelihood supervised
      solution (?lambda = 0) is characterized by many local optima. A modified form of
      the homotopy map for HMMs assures a track from ?lambda = 0 to ?lambda = 1.
      Following this track leads to a formulation for selecting ?lambda ?in [0, 1) for
      a semisupervised solution and it also provides a tool for selection from among
      multiple local-optimal supervised solutions. The results of applying the proposed
      method to measured and synthetic sequential data verify its robustness and
      feasibility compared to the conventional EM approach for semisupervised HMM
      training.

PMID- 19110494
TI  - Outlier detection with the kernelized spatial depth function.
AB  - Statistical depth functions provide from the "deepest" point a "center-outward
      ordering" of multidimensional data. In this sense, depth functions can measure
      the "extremeness" or "outlyingness" of a data point with respect to a given data
      set. Hence, they can detect outliers--observations that appear extreme relative
      to the rest of the observations. Of the various statistical depths, the spatial
      depth is especially appealing because of its computational efficiency and
      mathematical tractability. In this article, we propose a novel statistical depth,
      the kernelized spatial depth (KSD), which generalizes the spatial depth via
      positive definite kernels. By choosing a proper kernel, the KSD can capture the
      local structure of a data set while the spatial depth fails. We demonstrate this
      by the half-moon data and the ring-shaped data. Based on the KSD, we propose a
      novel outlier detection algorithm, by which an observation with a depth value
      less than a threshold is declared as an outlier. The proposed algorithm is simple
      in structure: the threshold is the only one parameter for a given kernel. It
      applies to a one-class learning setting, in which "normal" observations are given
      as the training data, as well as to a missing label scenario, where the training
      set consists of a mixture of normal observations and outliers with unknown
      labels. We give upper bounds on the false alarm probability of a depth-based
      detector. These upper bounds can be used to determine the threshold. We perform
      extensive experiments on synthetic data and data sets from real applications. The
      proposed outlier detector is compared with existing methods. The KSD outlier
      detector demonstrates a competitive performance.

PMID- 19110495
TI  - Time warp edit distance with stiffness adjustment for time series matching.
AB  - In a way similar to the string-to-string correction problem, we address discrete
      time series similarity in light of a time-series-to-time-series-correction
      problem for which the similarity between two time series is measured as the
      minimum cost sequence of edit operations needed to transform one time series into
      another. To define the edit operations, we use the paradigm of a graphical
      editing process and end up with a dynamic programming algorithm that we call Time
      Warp Edit Distance (TWED). TWED is slightly different in form from Dynamic Time
      Warping (DTW), Longest Common Subsequence (LCSS), or Edit Distance with Real
      Penalty (ERP) algorithms. In particular, it highlights a parameter that controls
      a kind of stiffness of the elastic measure along the time axis. We show that the
      similarity provided by TWED is a potentially useful metric in time series
      retrieval applications since it could benefit from the triangular inequality
      property to speed up the retrieval process while tuning the parameters of the
      elastic measure. In that context, a lower bound is derived to link the matching
      of time series into downsampled representation spaces to the matching into the
      original space. The empiric quality of the TWED distance is evaluated on a simple
      classification task. Compared to Edit Distance, DTW, LCSS, and ERP, TWED has
      proved to be quite effective on the considered experimental task.

PMID- 19110496
TI  - Framework for performance evaluation of face, text, and vehicle detection and
      tracking in video: data, metrics, and protocol.
AB  - Common benchmark data sets, standardized performance metrics, and baseline
      algorithms have demonstrated considerable impact on research and development in a
      variety of application domains. These resources provide both consumers and
      developers of technology with a common framework to objectively compare the
      performance of different algorithms and algorithmic improvements. In this paper,
      we present such a framework for evaluating object detection and tracking in
      video: specifically for face, text, and vehicle objects. This framework includes
      the source video data, ground-truth annotations (along with guidelines for
      annotation), performance metrics, evaluation protocols, and tools including
      scoring software and baseline algorithms. For each detection and tracking task
      and supported domain, we developed a 50-clip training set and a 50-clip test set.
      Each data clip is approximately 2.5 minutes long and has been completely
      spatially/temporally annotated at the I-frame level. Each task/domain, therefore,
      has an associated annotated corpus of approximately 450,000 frames. The scope of
      such annotation is unprecedented and was designed to begin to support the
      necessary quantities of data for robust machine learning approaches, as well as a
      statistically significant comparison of the performance of algorithms. The goal
      of this work was to systematically address the challenges of object detection and
      tracking through a common evaluation framework that permits a meaningful
      objective comparison of techniques, provides the research community with
      sufficient data for the exploration of automatic modeling techniques, encourages
      the incorporation of objective evaluation into the development process, and
      contributes useful lasting resources of a scale and magnitude that will prove to
      be extremely useful to the computer vision research community for years to come.

PMID- 19110497
TI  - Information geometry for landmark shape analysis: unifying shape representation
      and deformation.
AB  - Shape matching plays a prominent role in the comparison of similar structures. We
      present a unifying framework for shape matching that uses mixture models to
      couple both the shape representation and deformation. The theoretical foundation
      is drawn from information geometry wherein information matrices are used to
      establish intrinsic distances between parametric densities. When a parameterized
      probability density function is used to represent a landmark-based shape, the
      modes of deformation are automatically established through the information matrix
      of the density. We first show that given two shapes parameterized by Gaussian
      mixture models (GMMs), the well-known Fisher information matrix of the mixture
      model is also a Riemannian metric (actually, the Fisher-Rao Riemannian metric)
      and can therefore be used for computing shape geodesics. The Fisher-Rao metric
      has the advantage of being an intrinsic metric and invariant to
      reparameterization. The geodesicacomputed using this metricaestablishes an
      intrinsic deformation between the shapes, thus unifying both shape representation
      and deformation. A fundamental drawback of the Fisher-Rao metric is that it is
      not available in closed form for the GMM. Consequently, shape comparisons are
      computationally very expensive. To address this, we develop a new Riemannian
      metric based on generalized ?phi-entropy measures. In sharp contrast to the
      Fisher-Rao metric, the new metric is available in closed form. Geodesic
      computations using the new metric are considerably more efficient. We validate
      the performance and discriminative capabilities of these new information geometry
      based metrics by pairwise matching of corpus callosum shapes. We also study the
      deformations of fish shapes that have various topological properties. A
      comprehensive comparative analysis is also provided using other landmark-based
      distances, including the Hausdorff distance, the Procrustes metric, landmark
      based diffeomorphisms, and the bending energies of the thin-plate (TPS) and
      Wendland splines.

PMID- 19110498
TI  - Principal angles separate subject illumination spaces in YDB and CMU-PIE.
AB  - The theory of illumination subspaces is well developed and has been tested
      extensively on the Yale Face Database B (YDB) and CMU-PIE (PIE) data sets. This
      paper shows that if face recognition under varying illumination is cast as a
      problem of matching sets of images to sets of images, then the minimal principal
      angle between subspaces is sufficient to perfectly separate matching pairs of
      image sets from nonmatching pairs of image sets sampled from YDB and PIE. This is
      true even for subspaces estimated from as few as six images and when one of the
      subspaces is estimated from as few as three images if the second subspace is
      estimated from a larger set (10 or more). This suggests that variation under
      illumination may be thought of as useful discriminating information rather than
      unwanted noise.

PMID- 19110499
TI  - High-precision boundary length estimation by utilizing gray-level information.
AB  - We present a novel method that provides an accurate and precise estimate of the
      length of the boundary (perimeter) of an object by taking into account gray
      levels on the boundary of the digitization of the same object. Assuming a model
      where pixel intensity is proportional to the coverage of a pixel, we show that
      the presented method provides error-free measurements of the length of straight
      boundary segments in the case of nonquantized pixel values. For a more realistic
      situation, where pixel values are quantized, we derive optimal estimates that
      minimize the maximal estimation error. We show that the estimate converges toward
      a correct value as the number of gray levels tends toward infinity. The method is
      easy to implement; we provide the complete pseudocode. Since the method utilizes
      only a small neighborhood, it is very easy to parallelize. We evaluate the
      estimator on a set of concave and convex shapes with known perimeters, digitized
      at increasing resolution. In addition, we provide an example of applicability of
      the method on real images, by suggesting appropriate preprocessing steps and
      presenting results of a comparison of the suggested method with other local
      approaches.

PMID- 19110500
TI  - Statistical instance-based pruning in ensembles of independent classifiers.
AB  - The global prediction of a homogeneous ensemble of classifiers generated in
      independent applications of a randomized learning algorithm on a fixed training
      set is analyzed within a Bayesian framework. Assuming that majority voting is
      used, it is possible to estimate with a given confidence level the prediction of
      the complete ensemble by querying only a subset of classifiers. For a particular
      instance that needs to be classified, the polling of ensemble classifiers can be
      halted when the probability that the predicted class will not change when taking
      into account the remaining votes is above the specified confidence level.
      Experiments on a collection of benchmark classification problems using
      representative parallel ensembles, such as bagging and random forests, confirm
      the validity of the analysis and demonstrate the effectiveness of the instance
      based ensemble pruning method proposed.

PMID- 19110501
TI  - Camera displacement via constrained minimization of the algebraic error.
AB  - This paper proposes a new approach to estimate the camera displacement of stereo
      vision systems via minimization of the algebraic error over the essential
      matrices manifold. The proposed approach is based on the use of homogeneous forms
      and linear matrix inequality (LMI) optimizations, and has the advantages of not
      presenting local minima and not introducing approximations of nonlinear terms.
      Numerical investigations carried out with both synthetic and real data show that
      the proposed approach provides significantly better results than SVD methods as
      well as minimizations of the algebraic error over the essential matrices manifold
      via both gradient descent and simplex search algorithms.

PMID- 19110502
TI  - High-accuracy and robust localization of large control markers for geometric
      camera calibration.
AB  - Accurate measurement of the position of features in an image is subject to a
      fundamental compromise: The features must be both small, to limit the effect of
      nonlinear distortions, and large, to limit the effect of noise and
      discretization. This constrains both the accuracy and the robustness of image
      measurements, which play an important role in geometric camera calibration as
      well as in all subsequent measurements based on that calibration. In this paper,
      we present a new geometric camera calibration technique that exploits the
      complete camera model during the localization of control markers, thereby
      abolishing the marker size compromise. Large markers allow a dense pattern to be
      used instead of a simple disc, resulting in a significant increase in accuracy
      and robustness. When highly planar markers are used, geometric camera calibration
      based on synthetic images leads to true errors of 0.002 pixels, even in the
      presence of artifacts such as noise, illumination gradients, compression,
      blurring, and limited dynamic range. The camera parameters are also accurately
      recovered, even for complex camera models.

PMID- 19110504
TI  - Phosphorylation of myosin regulatory light chain by myosin light chain kinase,
      and muscle contraction.
AB  - Not only muscle contraction, but also most cell movements depend on myosin -
      actin interaction using ATP. Many components of the contraction machinery are
      involved in the efficient coupling of energy source and force development. Among
      these, I have focused on myosin light chain kinase (MLCK) in this review. MLCK
      phosphorylates myosin regulatory light chain and controls all 3 types of muscle
      contraction: skeletal muscle, smooth muscle, and cardiac muscle. However, each
      muscle has specific MLCK and the role of MLCK in each muscle is different. This
      difference explains the specific role of each muscle in vivo and contributes to
      the activity of various force development in different ways in each tissue.
      Therefore, I also review the differences in the connection between each MLCK and
      muscle contraction in the 3 muscle types.

PMID- 19110503
TI  - Novel aspects of oxidative stress in cardiovascular diseases.
AB  - Oxygen radicals, and other reactive oxygen species, may play an important role in
      the pathophysiology of atherosclerosis, stroke, and other cardiovascular
      diseases. Mechanisms that account for oxidative stress in different
      cardiovascular diseases are diverse; for example, increases in activity of
      NAD(P)H oxidase, "uncoupling" of nitric oxide synthase, and maladaptive changes
      in expression of antioxidants can all contribute to increases in oxidative
      stress. Very different patterns of pro-and antioxidant mechanisms that contribute
      to increases in oxygen radicals in atherosclerotic plaques, hemorrhagic strokes,
      and aortic valve stenosis have been observed. A disappointment, in relation to
      the hypothesis that oxygen radicals contribute to cardiovascular risk, is that
      many studies indicate that antioxidant vitamins fail to reduce the risk of
      cardiovascular disease. Better understanding of mechanisms that lead to increases
      in oxidative stress in different cardiovascular diseases may lead to more
      effective antioxidant prevention or treatment of diseases.

PMID- 19110505
TI  - Treatment with statin on atheroma regression evaluated by intravascular
      ultrasound with Virtual Histology (TRUTH Study): rationale and design.
AB  - BACKGROUND: Many clinical trials have shown that 3-hydroxy-3-methylglutaryl
      conenzyme A reductase inhibitors (statins) can significantly reduce the incidence
      of coronary artery disease in both primary and secondary prevention. A recent
      study showed that aggressive lipid-lowering therapy with statins could achieve
      regression of coronary artery plaque evaluated with gray-scale intravascular
      ultrasound (IVUS). However, the actual changes in coronary artery plaque
      composition produced by statin therapy have not been well delineated. METHODS AND
      RESULTS: This study will be a prospective, open-label, randomized multicenter
      study of 160 patients with stable or unstable angina who have undergone
      percutaneous coronary intervention with Virtual Histology IVUS (VH-IVUS).
      Patients will be randomly assigned to either the pitavastatin or pravastatin
      group. After treatment for 24-40 weeks, VH-IVUS will be performed again in the
      same segment of the coronary artery. The primary endpoint will be quantitative
      changes in each of the 4 components measured by VH-IVUS. CONCLUSION: The
      treatment with statin on atheroma regression evaluated by intravascular
      ultrasound with Virtual Histology (TRUTH) study will be the first multicenter
      study using VH-IVUS to evaluate the effects of statins on changes in coronary
      artery plaque composition and the findings will clarify the mechanisms of
      coronary artery plaque stabilization.

PMID- 19110506
TI  - Molecular and electrical remodeling of L- and T-type Ca(2+) channels in rat right
      atrium with monocrotaline-induced pulmonary hypertension.
AB  - BACKGROUND: Atrial arrhythmia is often encountered in chronic pulmonary disease
      with pulmonary hypertension (PH), but few studies have investigated the
      electrical remodeling of atrial Ca(2+) channels under PH. METHODS AND RESULTS:
      Wistar rats were injected with monocrotaline (MCT), resulting in PH with right
      atrial and ventricular hypertrophy. The L-type Ca(2+) channel current density was
      significantly decreased in right atrial cells of MCT-treated rats, accompanied by
      a significant reduction in mRNA expression of the CaV1.2 (alpha(1C)) subunit and
      accessory beta(2) subunit. Conversely, the low voltage-activated Ca(2+) current
      was more marked in the right atrial cells of MCT-treated rats than in those of
      control rats. The current-voltage relationship and the time course of
      inactivation closely resembled those of T-type Ca(2+) channels, although the
      current was only slightly inhibited by 10-100 micromol/L Ni(2+). No significant
      differences were observed in the mRNA expression levels of CaV3.1 (alpha(1G)) and
      CaV3.2 (alpha(1H)) or the protein level of the CaV3.1 subunit. In left atrial
      cells, the electrophysiological molecular properties of Ca(2+) channels were
      unaffected by MCT treatment. CONCLUSIONS: PH causes right atrial hypertrophy,
      associated with alteration of the electrophysiological molecular properties of
      Ca(2+) channels.

PMID- 19110507
TI  - Change in blood pressure just after initiation of cardiac resynchronization
      therapy predicts long-term clinical outcome in patients with advanced heart
      failure.
AB  - BACKGROUND: The aim of this study was to retrospectively investigate the long
      term effect of cardiac resynchronization therapy (CRT) and to clarify the useful
      predictors of clinical outcome. Methods and Results The study group comprised 43
      patients with advanced heart failure who underwent CRT (10 females; 66+/-10
      years): 23 were in sinus rhythm (SR group) and 20 had chronic atrial fibrillation
      (AF group). The clinical parameters and echocardiographic data were evaluated
      before and after CRT. There were no significant differences in the clinical
      parameters, echocardiographic data at baseline or frequency of responders between
      the 2 groups. In both groups, the clinical characteristics at baseline did not
      differ between the responders and non-responders. A prompt rise in systolic blood
      pressure (SBP) just after CRT was observed more often in responders than in non
      responders, and SBP rise > or =5 mmHg was the only significant independent
      predictor of a CRT responder (P=0.0033). Furthermore, there was a significant
      difference in the event-free survival between patients with and without SBP rise
      > or =5 mmHg, demonstrated by Kaplan-Meier method, at 2 years of follow-up
      (P=0.045). Conclusion A prompt BP rise just after CRT may predict short- and long
      term clinical improvement in CRT recipients.

PMID- 19110509
TI  - Brugada phenotype and prostate cancer.

PMID- 19110510
TI  - Non-stress echocardiographic diagnosis of coronary artery stenosis: changing
      viewpoints from systole to diastole.

PMID- 19110511
TI  - Diagnosis of unruptured intracranial aneurysms: 3T MR angiography versus 64
      channel multi-detector row CT angiography.
AB  - BACKGROUND AND PURPOSE: We compared 3-dimensional time-of-flight magnetic
      resonance angiography (3D TOF MRA) using a 3-tesla (T) MR unit with 64-channel
      multi-detector row computed tomographic angiography (64-MDCTA) for detection and
      characterization of angiographically proven unruptured intracranial aneurysms.
      METHODS: Thirty-eight patients with 47 aneurysms and 8 patients without aneurysms
      underwent 3T, 3D TOF MRA; 64-MDCTA; and intra-arterial angiography. As a first
      study, 3 radiologists blinded to pertinent clinical information independently
      reviewed MRA and CTA images. We evaluated diagnostic accuracy using an
      alternative free-response receiver operating characteristic (AFROC) analysis and
      evaluated the sensitivity and specificity of each technique. Next, 2 radiologists
      used volume-rendering images generated from MRA or CTA data to evaluate the
      morphology of the 47 aneurysms detected, and MRA and CTA results were compared.
      Three-dimensional digital angiography (DA) images were used as the standard of
      reference. RESULTS: On the AFROC analysis, the value of the mean area under the
      AFROC curve (A(1)) was 0.91 for both modalities. Mean sensitivity of 89% and
      specificity of 76% for MRA were not significantly different from sensitivity of
      87% and specificity of 79% for CTA. Therefore, when used to evaluate aneurysmal
      morphology, both modalities appear satisfactory for determining these vascular
      anomalies. CONCLUSION: Three-tesla, 3D TOF MRA and 64-MDCTA are excellent
      modalities with high diagnostic accuracy for evaluating unruptured intracranial
      aneurysms and no significant difference between them in diagnostic performance.

PMID- 19110512
TI  - A simple method for quantitative measurement and analysis of hyperpolarized
      (129)Xe uptake dynamics in mouse brain under controlled flow.
AB  - We established a simple method for measuring and quantifying uptake dynamics of
      hyperpolarized (HP) (129)Xe in mouse brain, which includes application of a
      saturation recovery pulse sequence under controlled flow of HP (129)Xe. The
      technique allows pursuit of the time-dependent change in (129)Xe nuclear magnetic
      resonance signal in the uptake process without effect from radiofrequency
      destruction of the polarization and the dynamics in mouse lung. The uptake
      behavior is well described by a simple model that depends only on a decay rate
      constant comprising cerebral blood flow and the longitudinal relaxation rate of
      HP (129)Xe in the brain tissue. The improved analysis enabled precise
      determination of the decay rate constant as 0.107+/-0.013 s(-1) (+/-standard
      deviation, n=5), leading to estimation of longitudinal relaxation time, T(1i), as
      15.3+/-3.5 s.

PMID- 19110513
TI  - Numerical simulation model of hyperacute/acute stage white matter infarction.
AB  - PURPOSE: Although previous studies have revealed the mechanisms of changes in
      diffusivity (apparent diffusion coefficient [ADC]) in acute brain infarction,
      changes in diffusion anisotropy (fractional anisotropy [FA]) in white matter have
      not been examined. We hypothesized that membrane permeability as well as axonal
      swelling play important roles, and we therefore constructed a simulation model
      using random walk simulation to replicate the diffusion of water molecules.
      MATERIALS AND METHODS: We implemented a numerical diffusion simulation model of
      normal and infarcted human brains using C++ language. We constructed this 2-pool
      model using simple tubes aligned in a single direction. Random walk simulation
      diffused water. Axon diameters and membrane permeability were then altered in
      step-wise fashion. To estimate the effects of axonal swelling, axon diameters
      were changed from 6 to 10 microm. Membrane permeability was altered from 0% to
      40%. Finally, both elements were combined to explain increasing FA in the
      hyperacute stage of white matter infarction. RESULTS: The simulation demonstrated
      that simple water shift into the intracellular space reduces ADC and increases
      FA, but not to the extent expected from actual human cases (ADC approximately
      50%; FA approximately +20%). Similarly, membrane permeability alone was
      insufficient to explain this phenomenon. However, a combination of both factors
      successfully replicated changes in diffusivity indices. CONCLUSION: Both axonal
      swelling and reduced membrane permeability appear important in explaining changes
      in ADC and FA based on eigenvalues in hyperacute-stage white matter infarction.

PMID- 19110514
TI  - Circumscribed mass lesions on mammography: dynamic contrast-enhanced MR imaging
      to differentiate malignancy and benignancy.
AB  - PURPOSE: We evaluated the magnetic resonance (MR) features of breast lesions
      showing circumscribed mass on mammography to understand the characteristics that
      differentiate malignancy and benignancy. MATERIALS AND METHODS: Our institutional
      review board approved the study, and informed consent was waived. Using logistic
      regression analysis, we examined morphologic and kinetic MR imaging data of 90
      breast lesions (43 malignant, 47 benign) that showed circumscribed mass on
      mammography. RESULTS: Features identified as having high odds for malignancy
      included: rim enhancement (odds ratio, 70.894; 95% confidence interval (CI),
      7.525-667.938); heterogeneous enhancement (odds ratio, 10.839; 95% CI, 1.032
      113.856); and washout dynamic pattern (odds ratio, 46.262; 95% CI, 3.716
      575.901). Combinations of washout dynamic pattern and either rim or heterogeneous
      enhancement reflected excessively high prediction probability for malignancy
      (>0.95), whereas combinations lacking washout dynamic pattern and with either
      homogeneous enhancement or dark internal septation revealed excessively low
      prediction probability for malignancy (<0.05). CONCLUSION: Breast cancers with
      circumscribed mass on mammography could be differentiated from benign masses
      using internal enhancement and the kinetic pattern of contrast-enhanced breast MR
      imaging.

PMID- 19110515
TI  - Visualization of neuromelanin in the Substantia nigra and locus ceruleus at 1.5T
      using a 3D-gradient echo sequence with magnetization transfer contrast.
AB  - Recent technical advances have enabled the visualization of neuromelanin in the
      substantia nigra pars compacta (SNc) and locus ceruleus (LC) by 3-tesla (T)
      magnetic resonance imaging in vivo. In the present study, we successfully
      detected neuromelanin in the SNc and LC of 6 healthy volunteers at 1.5T using a
      3D gradient echo sequence with off-resonance magnetization transfer contrast.

PMID- 19110516
TI  - MR imaging of fetal omphalocele: a case report.
AB  - We report a case of a fetal omphalocele in which the internal structure of the
      hernia sac was imaged in detail by magnetic resonance (MR) imaging. The hernia
      sac consisted of amnion, Wharton jelly, and externally, peritoneum. The umbilical
      vascular channels (2 arteries, one vein) were surrounded by Wharton jelly. Use of
      MR imaging facilitates a more accurate evaluation of fetal omphalocele with
      regard to hernial sac, intestinal structure, and differential diagnosis.

PMID- 19110518
TI  - [Non-side population hematopoietic stem cells in mouse bone marrow].

PMID- 19110519
TI  - [Cord blood transplantation for acute lymphoblastic leukemia in children:
      analysis at a single institution].
AB  - We examined the result of cord blood transplantation (CBT) for acute
      lymphoblastic leukemia (ALL) in children. Fifty ALL patients underwent stem cell
      transplantation in our hospital. Among these, 23 patients received related bone
      marrow transplantation and peripheral blood stem cell transplantation (R
      BMT/PBSCT), 17 patients received unrelated bone marrow transplantation (U-BMT),
      and 10 patients received unrelated cord blood transplantation (U-CBT). The 5-year
      overall survival rates after R-BMT/PBSCT, U-BMT and U-CBT were 64.6%, 32.3%, and
      85.7%, respectively. Event-free survivals after 5 years were 59.6%, 14.7%, and
      70.0%, respectively. The relapse rate in the U-CBT group was equal to that in the
      R-BMT/PBSCT group, and the transplant-related mortality of U-CBT was 0%. Our data
      show that U-CBT should be the first choice for patients with refractory or
      relapsed ALL who have no related HLA-matched donor.

PMID- 19110520
TI  - [Analysis of multiple cancers in autopsy cases of elderly hematological
      malignancies].
AB  - To investigate the actual situation of multiple cancers including hematological
      malignancies, 266 autopsy cases with one or more hematological malignancies were
      compiled from autopsy case files between January 1995 and October 2006 in our
      hospital. The median age at death was 75 years (range 48 to 102 yr). Of 266
      cases, 72 (27.1%) had multiple cancers. Of these 72 cases, 62 cases were
      complicated with non-hematological malignancy, and 10 cases showed duplication of
      other hematological malignancies. Prostate and colon cancers were frequent as
      complicating cancers. Seventeen of 256 cases without duplication of other
      hematological malignancies demonstrated 3 or 4 cancers (6.6%). Of 10 cases
      showing duplication of other hematological malignancies, 9 cases had NHL. The
      rate of multiple cancers in elderly patients with hematological malignancy was
      higher than that of non-hematological cancers.

PMID- 19110521
TI  - [Asymmetric peripheral neuropathy following reduced-intensity cord blood
      transplantation].
AB  - A 57-year-old male patient in the first remission of acute erythroid leukemia
      underwent reduced-intensity umbilical cord blood transplantation. He developed
      grade III acute graft-versus-host disease (GVHD) on day 29. Although the acute
      GVHD was resolved with tacrolimus and steroid therapy, weakness developed in the
      left upper extremity on day 59. Neurological examination demonstrated asymmetric
      muscular weakness of the extremities with the proximal part of the left upper
      extremity being markedly affected. Neurophysiological studies suggested that this
      was due to immune-mediated demyelinating neuropathy. Intravenous immunoglobulin
      (IVIG) therapy was administered at a dose of 0.4 g/kg/day for 5 days and
      worsening of clinical symptoms ceased. While the patient developed diarrhea and
      chronic GVHD of the skin and cytomegalovirus (CMV) antigenemia was repeatedly
      positive, neurological exacerbation was stabilized. Neurological symptoms did not
      immediately improve after the second and third dose of IVIG. Approximately 50
      days after the third dose of IVIG, neurological symptoms improved with the
      gradual resolution of diarrhea and CMV reactivation. Although the pathophysiology
      of polyneuropathies after allo-SCT is not well understood, some reports suggest
      an association with GVHD or alloreactive T cell expansion following antecedent
      infection. This case provides valuable information regarding the pathophysiology
      of peripheral neuropathy following allo-SCT.

PMID- 19110522
TI  - [Megaloblastic anemia associated with salazosulfapyridine treatment for
      rheumatoid arthritis].
AB  - A 70-year-old man was diagnosed as having rheumatoid arthritis (RA) in 2005. He
      was treated with 1 g salazosulfapyridine (SASP) daily for two years.
      Hematological investigations conducted since 2005 demonstrated hemoglobin
      concentrations of 8 approximately 9 g/dl, which then dropped to 4.9 g/dl on
      November 21, 2007, following which he was admitted to our hospital. Megaloblastic
      anemia associated with SASP treatment and anemia of chronic disorders were
      diagnosed on the basis of folate deficiency and bone marrow examination. This
      report describes a case of megaloblastic anemia, which developed two years after
      starting SASP and promptly recovered after its withdrawal and treatment with
      folic acid and prednisolone. The doses of SASP prescribed for RA in Japan are
      less than those prescribed abroad. Megaloblastic anemia associated with SASP
      treatment for RA is not usually detected in Japan. Currently, SASP is widely used
      and one of the key drugs in the treatment of RA. This case suggests that SASP
      therapy in RA might result in megaloblastic anemia.

PMID- 19110523
TI  - [Usefulness of immunofluorescence analysis of neutrophil nonmuscle myosin heavy
      chain-A for diagnosing in two sisters with May-Hegglin anomaly].
AB  - May-Hegglin anomaly (MHA) is a rare autosomal dominant disorder characterized by
      thrombocytopenia, giant platelets, and unique leukocyte inclusion bodies. The
      diagnosis of MHA has been made by identifying leukocyte inclusion bodies on May
      Giemsa stained blood film, however, it is not always easy to detect these
      findings. Therefore, patients with MHA are often misdiagnosed and managed as
      having idiopathic thrombocytopenic purpura. MHA is caused by mutations in the
      MYH9 gene, which encodes the nonmuscle mysosin heavy chain-A (NMMCH-A).
      Currently, MHA is definitively diagnosed by immunofluorescence study of leukocyte
      NMMHC-A localization and MYH9 gene analysis. In this study, we reported two
      sisters with MHA, who showed consistently decreased platelet counts and giant
      platelets. However, we could not detect inclusion bodies in their leukocytes.
      Immunofluorescence analysis of NMMHC-A in leukocytes of both sisters showed
      abnormal NMMHC-A localization. Furthermore, MYH9 gene analysis of both patients
      showed heterozygous R116C mutation in exon 26. Based on these findings, the two
      sisters were diagnosed as having MHA. Immunofluorescence analysis of neutrophil
      NMMHC-A is useful for diagnosis in patients without leukocyte inclusion bodies
      who are suspected of having MHA.

PMID- 19110524
TI  - [Splenic irradiation as a successful treatment for an elderly patient with B-cell
      prolymphocytic leukemia].
AB  - We report a case of B-cell prolymphocytic leukemia (B-PLL) that was treated
      successfully with splenic irradiation (SI). An 86-year-old man underwent a
      medical examination for lumbago and general fatigue at another hospital in June
      2007. A compressed lumbar fracture and splenomegaly were found using computed
      tomography (CT). Thereafter, the patient consulted our hospital because of
      leukocytosis. Peripheral blood showed hemoglobin level 9.8 g/dl and white blood
      cell count 38.1x10(9)/l with 91% atypical cells. Surface marker analysis
      demonstrated that atypical cells were positive for CD20, CD22, FMC7, surface IgM,
      surface IgD and kappa, but were negative for CD5, TdT and lambda. The morphology
      of these cells was compatible with prolymphocytes with prominent nucleoli and
      condensed nuclear chromatin. A diagnosis of B-PLL was made. SI (total dose 20 Gy)
      was chosen for the treatment and a single course of SI was very effective without
      causing any significant adverse events. This case demonstrates that SI may remain
      valuable for the treatment of B-PLL in an elderly patient.

PMID- 19110526
TI  - [Localized amyloidosis in the tonsil].
AB  - A 71-year-old male consulted our hospital complaining of right tonsil
      enlargement. Tonsillectomy was performed. Histological analysis demonstrated AL
      amyloid deposits obliterating the tonsillar structures. Foreign body giant cell
      reaction and morphologically normal plasma cells mainly containing light chain
      lambda were present around the amyloid. Serum immunoglobulin levels were normal
      and M-proteins were not detected. Urinary test for Bence Jones proteins was
      negative. Bone marrow aspirates did not demonstrate any signs of multiple
      myeloma. Amyloidosis of the stomach, colon, heart, and skin was ruled out. We
      report an extremely rare case of amyloidosis localized in the tonsil and review
      the literature.

PMID- 19110525
TI  - [Urgent hemostatic control with Confact F for ovarian bleeding complicated by an
      unknown type of von Willebrand disease].
AB  - Emergency surgery was performed on a 24-year-old female patient with an unknown
      type of von Willebrand disease (VWD). The patient suddenly developed lower
      abdominal pain and was transported to our hospital by ambulance. Based on the
      diagnosis of ovarian bleeding, emergency surgery was indicated. Ristocetin
      cofactor activity (VWF: RCo) was between 7% and 14% by measurement with von
      Willebrand reagent (Dade Behring, Marburg, Germany). A laparoscopic partial
      resection of the left ovary was performed under administration of factor VIII/VWF
      concentrate, Confact F((R)) (Chemo-Sero-Therapeutic Research Institute, Kumamoto,
      Japan). During and after surgery, there was no abnormal bleeding. The results
      obtained by measurement by the reagent were similar to the levels of VWF: RCo
      obtained by the fixed platelet agglutination method. The reagent was useful for
      diagnosing and monitoring the VWF: RCo level to control bleeding in VWD.

PMID- 19110527
TI  - [Thyrotoxicosis after cord blood transplantation for acute myelogenous leukemia].
AB  - We describe a 44-year-old man with acute myelogenous leukemia who developed
      thyrotoxicosis after unrelated cord blood transplantation. He complained of
      fever, general fatigue, tremor and tachycardia on day 63. On examination of
      thyroid function, free triiodothyronine (23.67 pg/ml) and free thyroxine (5.71
      ng/dl) were increased, and thyroid-stimulating hormone (<0.03 microU/ml) was
      decreased. Antithyroid receptor antibody, antithyroid peroxidase antibody and
      antithyroglobulin antibody were all negative. The patient was diagnosed as having
      thyrotoxicosis. His symptoms improved and thyroid function returned to the normal
      levels within 2 weeks. Thyrotoxicosis is a rare complication, but we should be
      aware that it may cause idiopathic fever after stem cell transplantation.

PMID- 19110528
TI  - [New investigation of the effect of toner and its by-products on human health and
      occupational health management of toner].
AB  - We need a new investigation of the effect of not only toner but also of its by
      products on human health, because of the generation of fine particles and the
      release of volatile organic compounds (VOC) in the process of photocopy.
      Therefore, we gathered epidemiological and animal data on toner and its by
      products, and examined the occupational health management of toner. We examined
      the effect of carbonblack as the main component of toner, and titanium dioxide
      and amorphous silica as surface-adhesive nanomaterials, and VOC on human health,
      and reviewed them. We summarize the results as follows. 1) High sensitive c
      reactive protein in serum, 8-hydroxydeoxyguanosine in urine, and heart rate
      variability (HRV) are useful for biological monitoring of exposure to toner and
      its by-products. 2) Particle number concentrations have been often measured by
      scanning mobility particle sizer (SMPS) compared with other apparatus, although
      this is not measurement gold standard. Taken together, we have examined whole
      occupational health management of toner and its by-products.

PMID- 19110529
TI  - Biology of chronic graft-versus-host disease: implications for a future
      therapeutic approach.
AB  - Hematopoietic cell transplantation (HCT) is frequently complicated by graft
      versus-host disease (GVHD). During the past three decades, experimental studies
      and clinical observations have elucidated the pathophysiology of acute GVHD, but
      the biology of chronic GVHD is much less well understood. Recommendations of the
      NIH Consensus Development Project on Criteria for Clinical Trials in Chronic GVHD
      have begun to standardize the diagnosis and clinical assessment of the disease.
      These criteria have emphasized the importance of qualitative differences, as
      opposed to time of onset after HCT, in making the distinction between acute and
      chronic GVHD. Experimental studies have generated at least four theories to
      explain the pathophysiology of chronic GVHD. These theories include 1) thymic
      damage and defective negative selection of T cells generated from marrow
      progenitors after HCT, 2) aberrant production of transforming growth factor-beta,
      3) auto-antibody production, and 4) deficiency of T-regulatory cells. Recent
      studies in humans have corroborated a possible role for each of these mechanisms
      in humans. No animal model fully replicates all of the features of chronic GVHD
      in humans, and it appears likely that multiple biological mechanisms account for
      the diverse features the disease. Chronic GVHD may represent a "syndrome" with
      diverse causes among individual patients. In the future, it might become possible
      to tailor specific therapeutic interventions for patients as individually needed
      for each distinct pathophysiologic mechanism involved in development of the
      disease.

PMID- 19110531
TI  - The effect of saffron (Crocus sativus) extract for healing of second-degree burn
      wounds in rats.
AB  - The aim of this study was to evaluate the efficacy of pollen of saffron extract
      cream in the treatment of thermal induced burn wounds and to compare its results
      with silver sulfadiazine (SSD) in rats. Animals were divided into four groups and
      administrated a topical cream including control, base, saffron (20%) or SSD (1%)
      at 24 hour after a burn injury that was induced by hot water. In special days,
      according to a pre-planned schedule, animal's weight, wound size, as well as skin
      histo-pathology were determined in different groups under topical treatments. On
      day 25, average size of wound was 5.5, 4, 0.9 and 4.1 cm2 in control, base,
      saffron and silver groups. The wound size of saffron group was significantly
      smaller than other groups. Histological comparison has shown that saffron
      significantly increased re-epithelialization in burn wounds, as compared to other
      cream-treated wounds. Although the exact mechanism of saffron is unclear, anti
      inflammatory and antioxidant effects of saffron may have contributed to the wound
      healing. The results of this study raise the possibility of potential efficacy of
      saffron in accelerating wound healing in burn injuries.

PMID- 19110530
TI  - A new role for the renin-angiotensin system in the development of the ureteric
      bud and renal collecting system.
AB  - The renin-angiotensin system (RAS) plays a critical role in kidney development.
      Mutations in the genes encoding components of the RAS or pharmacological
      inhibition of RAS in mice or humans cause a spectrum of congenital abnormalities
      of the kidney and urinary tract (CAKUT). The observed defects include renal
      vascular abnormalities, abnormal glomerulogenesis, renal papillary hypoplasia,
      hydronephrosis, aberrant ureteric bud (UB) budding, duplicated collecting system
      and renal tubular dysgenesis. Little is known about the potential role of Ang II
      and its receptors in the morphogenesis of the UB and renal collecting system.
      This review emphasizes a novel role for the RAS in the development of the UB,
      collecting ducts and renal medulla. We observe that UB and surrounding stroma
      express angiotensinogen and Ang II AT1 receptors (AT1R) in vivo. Ang II
      stimulates UB cell branching in collagen gel cultures in vitro and induces UB
      morphogenesis in intact whole embryonic metanephroi grown ex vivo. In contrast,
      treatment of metanephroi with the AT1R antagonist candesartan inhibits UB
      branching. In addition, Ang II induces tyrosine phosphorylation of the epidermal
      growth factor receptor (EGFR) in UB cells. Furthermore, Ang II-stimulated UB
      morphogenesis is abrogated by inhibition of EGFR tyrosine kinase activity. In
      summary: 1) Ang II, acting via the AT1R, stimulates UB branching; 2) This process
      depends on tyrosine phosphorylation of the EGFR. Together, these data indicate
      that cooperation of AT1R and EGFR signaling performs essential functions during
      renal collecting system development via control of UB branching morphogenesis.

PMID- 19110532
TI  - Deep venous thrombosis in stroke patients during rehabilitation phase.
AB  - PURPOSE: The purpose of this study was to examine the incidence, factors, and
      effects of antiplatelet and anticoagulant agents on sub-acute and chronic
      ischemic stroke patients during the rehabilitation phase for rates of deep venous
      thrombosis (DVT) from the perspective for rehabilitation medicine. METHODS: In
      this study of 272 patients undergoing rehabilitation for completed cerebral
      infarction, multiple circumference measurements of calf and thigh along with
      presence or absence of symptoms (congestion, swelling, skin redness, warmth,
      pain, pigmentation, fever and/or Homan sign or Luck's sign) documented in the
      physical examination were recorded in all patients. Patients with these symptoms
      suggestive of DVT were included for D-dimer assay and venous duplex
      ultrasonography to confirm presence of DVT. RESULTS: DVT was documented in 24
      patients (8.8%), most of whom displayed distal DVT on the hemiparetic side. A
      significant association was seen between occurrence of DVT and more severe lower
      limb paresis, manifesting as gait disturbance, severe calf muscle spasticity, use
      of ankle-foot orthosis (AFO). A significant increase in development of DVT was
      associated with severe spasticity in hemiparetic calf muscles (odds ratio (OR)
      28.2; 95% confidence interval (CI), 6.9-113.5). Cilostazol seemed to be the only
      effective antiplatelet drug for preventing DVT in cerebral infarction patients.
      CONCLUSION: Incidence of DVT in the rehabilitation phase following stroke was not
      low, which was predominant as distal DVT on the hemiparetic side. Lower limb
      paresis, gait disturbance, calf muscle spasticity and use of AFO contributed to
      occurrence of DVT. It is likely that micro-injuries in the venous endothelium due
      to spasticity and AFO might cause DVT. Cilostazol seems effective for protecting
      against venous endothelial damage following DVT.

PMID- 19110533
TI  - Correlations of anatomical parameters in dynamic pelvic CT and conventional
      defecography for patients with rectal prolapse.
AB  - PURPOSE: To evaluate the correlations of anatomical parameters between dynamic
      pelvic CT (D-PCT) and conventional defecography (CD) for patients with rectal
      prolapse. MATERIAL AND METHODS: Anatomical parameters in multislice CT scanning
      of the pelvis performed at rest and during simulated defecation (D-PCT) were
      studied with those of CD to evaluate the correlations in both methods for 10
      patients with rectal prolapse. RESULT: The correlation coefficients of the
      pubococcygeal line and the pubosacral line were r=0.6 and r=0.8 respectively. The
      length from anal verge to pubococcygeal line and to the pubosacral line showed a
      good correlation of r=0.7. The length of puborectal muscle showed a good
      correlation of r=0.8. Anorectal angle was significantly well correlated between
      two methods (r=0.9, p<0.05). The lengths of anococcygeal length and anosacral
      length showed a good correlation. CONCLUSION: The anatomical parameters measured
      by D-PCT were well correlated with those by CD. D-PCT might be an alternative
      tool for anatomical evaluation of the anorectal region in patients with rectal
      prolapse.

PMID- 19110534
TI  - Rat dorsal paired island skin flaps: a precise model for flap survival
      evaluation.
AB  - Rectangular flaps on the rat or mouse dorsum are frequently used for flap
      survival elongation research. However, since rectangular flaps are purely random,
      the survival rate varies among individuals. A reliable animal flap model with low
      individual variation is desirable for flap survival research, especially in the
      angiogenic field. We investigated the survival rate of paired flaps in the rat
      dorsum containing 3 vascular territories in each flap, and determined their
      usefulness for flap elongation research. Two symmetrical adjoining rectangular
      flaps (11 x 3 cm each) were drawn on the rat dorsum. Two days after material
      injection, flaps were elevated with only the deep circumflex iliac vessels as the
      vascular pedicle. Flaps were immediately sutured back and the flap survival area
      was measured 7 days after the operation. The control group (n = 9) had saline
      solution injected in both flaps. The bone marrow group (n = 8) had bone marrow
      injected in the right flap, and saline solution injected in the left flap. In the
      control group, the survival rate of the paired flaps was not statistically
      different (right flap, 89.0+/-5.6%; left flap, 89.3+/-4.5%). In the bone marrow
      group, the survival rate between the bone marrow injected flap (89.9+/-3.7%), and
      the saline flap (84.8+/-4.3%) was statistically different. The rat dorsal paired
      island skin flap model shows low difference in flap survival rate and uses an
      internal control. This is a suitable model for flap survival elongation research.

PMID- 19110535
TI  - Ascertaining causes of neonatal deaths using verbal autopsy: current methods and
      challenges.
AB  - OBJECTIVE: 'Verbal autopsy' (VA) is used to ascertain cause of death in countries
      where vital registration systems are lacking. Current VA methods for neonatal
      deaths vary widely and suffer from several limitations. We aimed to: (1) review
      current neonatal VA methods, (2) identify gaps and limitations, (3) illustrate
      some limitations using VA data and (4) identify new approaches in methodology and
      analysis. STUDY DESIGN: Rolling techniques and database search terms were used to
      identify articles that described neonatal VA administration, validation and cause
      of death assignment. RESULT: Current VA interviews include open and close-ended
      modules and are administered by trained interviewers. Causes of death are
      determined using physician review and/or computer algorithms for various neonatal
      causes of death. Challenges include lack of a standardized VA instrument and
      administration of methods, difficulty in identifying gold standards for
      validation studies, lack of validated algorithms for causes of death, poor
      existing algorithms, lack of standardized death classification terminology and
      the use of hierarchy to assign causes of death. Newer probabilistic methods of
      analysis such as Bayes Theorem or the Symptom Pattern method may improve accuracy
      for cause of death estimation and alleviate some of the challenges with
      traditional physician and algorithmic approaches, although additional research is
      needed. CONCLUSION: Given the continued reliance on VA to determine cause of
      death in settings with inadequate registration systems, it is important to
      understand the gaps in current VA methods and explore how methods can be improved
      to accurately reflect neonatal disease burden in the global community.

PMID- 19110536
TI  - Analysis of 17 autoimmune disease-associated variants in type 1 diabetes
      identifies 6q23/TNFAIP3 as a susceptibility locus.
AB  - As a result of genome-wide association studies in larger sample sets, there has
      been an increase in identifying genes that influence susceptibility to individual
      immune-mediated diseases, as well as evidence that some genes are associated with
      more than one disease. In this study, we tested 17 single nucleotide
      polymorphisms (SNP) from 16 gene regions that have been reported in several
      autoimmune diseases including rheumatoid arthritis (RA), systemic lupus
      erythematosus (SLE), multiple sclerosis (MS), ankylosing spondylitis (AS) and
      Crohn's disease (CD) to determine whether the variants are also associated with
      type 1 diabetes (T1D). In up to 8010 cases and 9733 controls we found some
      evidence for an association with T1D in the regions containing genes: 2q32/STAT4,
      17q21/STAT3, 5p15/ERAP1 (ARTS1), 6q23/TNFAIP3 and 12q13/KIF5A/PIP4K2C with
      allelic P-values ranging from 3.70 x 10(-3) to 3.20 x 10(-5). These findings
      extend our knowledge of susceptibility locus sharing across different autoimmune
      diseases, and provide convincing evidence that the RA/SLE locus 6q23/TNFAIP3 is a
      newly identified T1D locus.

PMID- 19110537
TI  - Genetic, epidemiological and biological analysis of interleukin-10 promoter
      single-nucleotide polymorphisms suggests a definitive role for -819C/T in leprosy
      susceptibility.
AB  - Leprosy is a complex infectious disease influenced by genetic and environmental
      factors. The genetic contributing factors are considered heterogeneous and
      several genes have been consistently associated with susceptibility like PARK2,
      tumor necrosis factor (TNF), lymphotoxin-alpha (LTA) and vitamin-D receptor
      (VDR). Here, we combined a case-control study (374 patients and 380 controls),
      with meta-analysis (5 studies; 2702 individuals) and biological study to test the
      epidemiological and physiological relevance of the interleukin-10 (IL-10) genetic
      markers in leprosy. We observed that the -819T allele is associated with leprosy
      susceptibility either in the case-control or in the meta-analysis studies.
      Haplotypes combining promoter single-nucleotide polymorphisms also implicated a
      haplotype carrying the -819T allele in leprosy susceptibility (odds ratio
      (OR)=1.40; P=0.01). Finally, we tested IL-10 production in peripheral blood
      mononuclear cells stimulated with Mycobacterium leprae antigens and found that 
      819T carriers produced lower levels of IL-10 when compared with non-carriers.
      Taken together, these data suggest that low levels of IL-10 during the disease
      outcome can drive patients to a chronic and unprotective response that culminates
      with leprosy.

PMID- 19110538
TI  - A comprehensive review on salt and health and current experience of worldwide
      salt reduction programmes.
AB  - Cardiovascular disease (CVD) is the leading cause of death and disability
      worldwide. Raised blood pressure (BP), cholesterol and smoking, are the major
      risk factors. Among these, raised BP is the most important cause, accounting for
      62% of strokes and 49% of coronary heart disease. Importantly, the risk is
      throughout the range of BP, starting at systolic 115 mm Hg. There is strong
      evidence that our current consumption of salt is the major factor increasing BP
      and thereby CVD. Furthermore, a high salt diet may have direct harmful effects
      independent of its effect on BP, for example, increasing the risk of stroke, left
      ventricular hypertrophy and renal disease. Increasing evidence also suggests that
      salt intake is related to obesity through soft drink consumption, associated with
      renal stones and osteoporosis and is probably a major cause of stomach cancer. In
      most developed countries, a reduction in salt intake can be achieved by a gradual
      and sustained reduction in the amount of salt added to food by the food industry.
      In other countries where most of the salt consumed comes from salt added during
      cooking or from sauces, a public health campaign is needed to encourage consumers
      to use less salt. Several countries have already reduced salt intake, for
      example, Japan (1960-1970), Finland (1975 onwards) and now the United Kingdom.
      The challenge is to spread this out to all other countries. A modest reduction in
      population salt intake worldwide will result in a major improvement in public
      health.

PMID- 19110539
TI  - Inulavosin, a melanogenesis inhibitor, leads to mistargeting of tyrosinase to
      lysosomes and accelerates its degradation.
AB  - The melanosome is a highly specialized organelle where melanin is synthesized.
      Tyrosinase and tyrosinase-related protein-1 (Tyrp1) are major melanosomal
      membrane proteins and key enzymes for melanin synthesis in melanocytes.
      Inulavosin, a melanogenesis inhibitor isolated from Inula nervosa (Compositae),
      reduced the melanin content without affecting either the enzymatic activities or
      the transcription of tyrosinase or Tyrp1 in B16 melanoma cells. To our knowledge,
      this inhibitor is previously unreported. Electron-microscopic analyses revealed
      that inulavosin impaired late-stage development of melanosomes (stages III and
      IV), in which melanin is heavily deposited. However, it did not alter the early
      stages of melanosomes (stages I and II), when filamentous structure is observed.
      Immunofluorescence analyses showed that tyrosinase, but not Tyrp1, was
      specifically eliminated from melanosomes in cells treated with inulavosin.
      Unexpectedly, inulavosin specifically accelerated the degradation of tyrosinase
      but not other melanosomal/lysosomal membrane proteins (Tyrp1, Pmel17, and LGP85).
      The degradation of tyrosinase induced by inulavosin associated with lysosomes but
      not the proteasome. Interestingly, lysosomal protease inhibitors restored the
      melanogenesis but not the targeting of tyrosinase to melanosomes in the cells
      treated with inulavosin. Instead, colocalization of tyrosinase with lysosome
      associated membrane protein-1 at late endosomes/multivesicular bodies and
      lysosomes was accentuated. Taken together, inulavosin inhibits melanogenesis as a
      result of mistargeting of tyrosinase to lysosomes.

PMID- 19110541
TI  - Prolactin and the skin: a dermatological perspective on an ancient pleiotropic
      peptide hormone.
AB  - The polypeptide hormone prolactin (PRL) is best known as the pituitary modulator
      of lactation and reproduction. However, based on the almost ubiquitous
      distribution of PRL receptors (PRLR) and an ever-growing list of extrapituitary
      PRL-expressing tissues, a vast range of PRL actions "beyond the mammary horizon"
      has now been documented or claimed. For example, PRL modulates hair growth in
      domestic animals with seasonal hair growth changes ("PRL-pelage axis"). Given
      that the mammary gland is an epidermal derivative, it is not surprising that the
      pilosebaceous unit, another epidermal derivative, has also surfaced as a
      prominent, PRLR-expressing, nonclassical PRL target organ. Moreover, the fact
      that murine and human hair follicles even synthesize PRL strongly invites one to
      explore fully the dermatological dimensions of this multifunctional, cytokine
      like neuroendocrine bioregulator, which remain insufficiently charted. After
      describing the relevant essentials of general PRL/PRLR biology, we summarize
      clinical observations that provide insights into how PRL may impact on the skin,
      and define important research frontiers and controversies in the quest to better
      characterize the complex role of PRL in human skin biology and pathology.
      Focusing on psoriasis, alopecia, and stress-related dermatoses, we then discuss
      the possible role of PRL/PRLR in cutaneous pathology, and identify potential
      therapeutic targets for the management of these skin disorders. We close by
      delineating major open questions at this emerging frontier of basic and clinical
      cutaneous neuroendocrinology, and argue that systematic exploration of the "PRL
      skin connection" will fertilize the development of previously unreported
      neuroendocrinological strategies for managing selected skin disorders.

PMID- 19110540
TI  - TIA nuclear proteins regulate the alternate splicing of lysyl hydroxylase 2.
AB  - Synthesis of collagen, a major component of the extracellular matrix, is
      increased dramatically in fibrotic conditions such as scleroderma. This
      overaccumulation of collagen is associated with increased pyridinoline cross
      links. These cross-links are derived by the action of the alternatively spliced
      long form of lysyl hydroxylase 2 (LH2), a collagen telopeptide LH. As LH2 (long)
      is reported to be overexpressed in scleroderma fibroblasts, the regulation of LH2
      splicing suggests an important step in controlling fibrosis. Using an LH2
      minigene, we have compared the regulation of the alternative splicing pattern of
      LH2, both endogenously and in the minigene, by the RNA-binding splicing proteins
      TIA-1 and TIAL1 (T-cell-restricted intracellular antigens). A decrease in the
      ratio of LH2 (long) to LH2 (short) was observed in fibroblasts from TIAL1
      knockout mice, and in HEK293 cells knocked down for TIA-1 and TIAL1. As a
      corollary, overexpression of TIA-1/TIAL1 in HEK293 cells resulted in an increase
      in LH2 (long) minigene transcripts, accompanied by a decrease in LH2 (short). In
      scleroderma fibroblasts, a double TIA-1/TIAL1 knockdown reduced the ratio of LH2
      (long) to LH2 (short) by over fivefold compared to controls. Identification of
      these TIA regulatory factors therefore suggests a tool to manipulate cellular LH2
      levels in scleroderma so that potential intervention therapies may be identified.

PMID- 19110542
TI  - The role of interleukin-6 in UVA protection against UVB-induced
      immunosuppression.
AB  - The proinflammatory cytokine IL-6 is released in the skin following UVB
      irradiation, but its potential for photoimmune modulation remains unclear. This
      study utilizes IL-6-deficient mice to demonstrate that IL-6 does not contribute
      to the normal contact hypersensitivity response, nor to its systemic suppression
      by UVB radiation or cis-urocanic acid. In contrast, IL-6 was required for the
      attenuation of UVB- or cis-urocanic acid-induced immunosuppression by sequential
      or concomitant UVA irradiation. The IL-6 was essential for several reactions
      previously established to be relevant for UVA photoimmune protection, namely the
      induction of heme oxygenase-1 (HO-1), the activity of its product carbon monoxide
      in activating guanylyl cyclase, and the consequent elevation of cutaneous cyclic
      guanosine monophosphate concentration. In addition, IL-6-deficient mouse skin had
      an elevated constitutive overexpression of HO activity, apparently not associated
      with photoimmune protection. This suggested that both the cutaneous level of HO
      activity, and the receptiveness of the HO-1 gene to stressors like UVA, normally
      controlled by promoter-binding repressor proteins, may also be under IL-6
      control. Thus IL-6 has an important photoimmune protective function through
      interaction at several levels in the pathway determining the immunologically
      advantageous actions of UVA radiation. This may constitute a valuable endogenous
      antiphotocarcinogenic regulatory mechanism.

PMID- 19110544
TI  - Effects of intermittent hypoxic training on orthostatic reactions of the
      cardiorespiratory system.
AB  - The possibility of using intermittent hypoxic training for stimulation of
      physiological mechanisms underlying the compensatory hemodynamic reactions to
      orthostatic load was studied in animal experiments. Intermittent hypoxic training
      had a favorable impact on circulatory reactions, which manifested in
      stabilization of blood pressure and heart filling pressure and in a decrease in
      orthostatic hypotension during the initial period of orthostasis. We hypothesized
      that the positive effect of intermittent hypoxic training on the correction of
      negative hemodynamic shifts is determined by the training effect aimed at the
      increase in the vascular tone and venous return to the heart. These results can
      serve as validation for preventive use of intermittent hypoxic training for
      reducing blood draining in the lower part of the body, correction of the
      compensatory orthostatic reaction of the circulatory system, and hence, for
      improvement of orthostatic resistance.

PMID- 19110543
TI  - Drug-virus interaction: effect of administration of recombinant adenoviruses on
      the pharmacokinetics of docetaxel in a rat model.
AB  - Modern cancer therapy combines recombinant viruses with traditional
      chemotherapeutic agents that are metabolized by hepatic cytochrome P450 3A4
      (CYP3A4). A single dose of recombinant adenovirus (Ad) expressing beta
      galactosidase (AdlacZ) significantly alters CYP3A2, the correlate of CYP3A4, in
      rats for 14 days. Recombinant adenovirus expressing human p53 (Adp53) also
      suppresses CYP3A2. Plasma clearance of docetaxel (DTX) in animals given AdlacZ
      (3.38+/-0.22 l h(-1) kg(-1)) was significantly lower than that of those given DTX
      alone (7.35+/-1.22 l h(-1) kg(-1), P<or=0.05). Area under the plasma
      concentration-time curve of DTX in rats given AdlacZ (2987.37+/-197.97 ng ml(-1)
      h(-1)) was significantly greater than those given drug alone (1496.14+/-281.62 ng
      ml(-1) h(-1), P<or=0.05). Both viruses prolonged DTX half-life (t(1/2)). Ad
      infection may cause significant variability in the pharmacokinetics and
      pharmacodynamics of anti-cancer agents and should be considered when designing
      therapeutic regimens for patients with viral infection and those enrolled in
      clinical trials using recombinant viruses.

PMID- 19110545
TI  - Electrical activity of no-producing neuron depends on NO level.
AB  - NO-producing neuron exhibited an excitatory response to the decrease in NO
      concentration, which was induced by NO synthase inhibitor N-nitro-L-arginine or
      specific NO acceptor 2-phenyl-4,4,5,5-tetramethylimidazoline-1-oxyl-3-oxide.
      Addition of NO donors to the medium inhibits neuronal activity. The excitatory
      effects of N-nitro-L-arginine and 2-phenyl-4,4,5,5-tetramethylimidazoline-1-oxyl
      3-oxide were preserved, while the inhibitory action of NO donors significantly
      decreased after isolation of the neuron. These findings indicate that NO
      regulates activity of these neurons by the negative feedback mechanism. This
      regulation includes the following complementary mechanisms: (1) endogenous
      mechanism of cell self-activation in response to the decrease in NO
      concentration; and (2) exogenous mechanism of cell-mediated inhibition in
      response to NO excess.

PMID- 19110546
TI  - Changes in stomach motor-secretory function during immobilization and pain stress
      and their correction with bioactive food supplement Lymphosan.
AB  - We studied the effects of immobilization and pain stress on motor and secretory
      function of the stomach in dogs and correction of these changes with bioactive
      supplement Lymphosan. The stress factors induced pronounced changes in
      physiological parameters: immobilization stress induced hypersecretion, while
      pain stress inhibited the glandular apparatus. In animals treated with Lymphosan,
      both stress factors produced less pronounced changes and motor and secretory
      functions of the stomach were near to the control level. Thus, when used as a
      corrector of stress reactions, Lymphosan produced adaptogenic effects on the
      stomach and normalized the stress-induced disturbances.

PMID- 19110547
TI  - Specific adrenergic responses of smooth muscles in the vascular wall of guinea
      pig pulmonary arteries during ovalbumin sensitization.
AB  - The adrenergic contractile responses of smooth muscles in the vascular wall of
      guinea pig pulmonary arteries were studied during ovalbumin sensitization.
      Sensitization was followed by inhibition of contractile responses to an alpha
      adrenoceptor agonist mesatone, prevented endothelium-derived relaxation, and
      potentiated the contractile response to isoproterenol. Administration of a beta
      adrenoceptor agonist isoproterenol potentiated the increase in mechanical strain
      of smooth muscles in the pulmonary artery precontracted with high-potassium Krebs
      solution. Removal of the endothelium had no effect on the contractile response of
      smooth muscle segments from the pulmonary artery of intact and sensitized guinea
      pigs to b-adrenergic influences. The contractile responses of smooth muscles of
      the pulmonary artery are associated with activity of the cAMP-dependent signal
      system and play a role in the pathogenesis of ventilation-perfusion disturbances
      during atopic inflammation.

PMID- 19110548
TI  - Delayed effects of the terms of separation of rat pups from lactating females and
      low-protein diet on enzyme activity in digestive and non-digestive organs.
AB  - Early and late separation of rat pups from lactating females and combined effects
      of the terms of separation and low-protein diet are essential for the formation
      of enzymes (maltase, alkaline phosphatase, aminopeptidase M, and glycyl-L-leucine
      dipeptidase) in the large and small intestine, liver and kidneys of adult
      animals. Similarities and differences in the enzyme reactions to early and late
      weaning and to a combination of untimely weaning and low-protein diet were
      detected.

PMID- 19110549
TI  - Effect of neuromedin on activity of lactate dehydrogenase in mitochondrial
      fraction of the brain in rats with thermal injury.
AB  - We studied enzyme systems (lactate dehydrogenase) of mitochondria in cerebral
      nerve cells in experimental encephalopathy developing after thermal injury. In
      animals receiving neuromedin at the early terms after injury, the ratio of
      forward to reverse lactate dehydrogenase reactions significantly increased over
      the first day after injury and returned to normal on day 7.

PMID- 19110550
TI  - Effects of granulocyte colony-stimulating factor and hyaluronidase on the
      formation of blood system reactions.
AB  - We studied the possibility of modification of hematotropic effects of
      granulocytic CSF and hyaluronidase. It was found that hyaluronidase in a dose of
      20 U/mouse potentiates the specific effect of granulocytic CSF on
      granulocytopoiesis, while granulocytic CSF potentiates the stimulating effect of
      the enzyme on the erythroid stem. Functional activity of hemopoiesis precursors,
      secretion of humoral factors by adherent myelokaryocytes, and serum content of
      hemopoietins increased under these conditions. Hyaluronidase (100 U/mouse)
      against the background of treatment with granulocytic CSF leads to uncoupling of
      proliferation and differentiation of hemopoietic cells and abolishes the mutually
      activating hematotropic effect of preparations.

PMID- 19110551
TI  - Experimental model of acute ischemia of the retina in rats.
AB  - We studied the development of retinal ischemia in rat eye after laser coagulation
      of blood vessels. Typical signs of ischemia manifested in the retina after 24 h:
      development of stable retinal edema, decrease in the b/a index (ratio of the
      electroretinogram b and a-wave amplitudes) to 1-2 units, pronounced disorders in
      the retinal microcirculation system, leading to ischemia of the inner layers of
      the retina. The proposed model is convenient for studies of the development of
      acute retinal ischemia, is easily realized, and reproduces some acute ischemic
      diseases of the retina.

PMID- 19110552
TI  - Cholesterol-induced stimulation of postinflammatory liver fibrosis.
AB  - We studied the effect of high-cholesterol diet and factors inhibiting 3-hydroxy-3
      methylglutaryl coenzyme A reductase on the development of liver fibrosis in
      C57Bl/6 mice with CCl4- or zymosan-induced hepatitis. Feeding a high-cholesterol
      diet led to a sharp increase in collagen content in the liver tissue of animals
      with CCl4-induced or zymosan-induced hepatitis. Atorvastatin and calcitriol
      produced less pronounced fibrogenic effects. Mevalonate partially prevented the
      development of cholesterol-induced fibrogenesis. High-cholesterol diet led to
      accumulation of oxysterols, cholesterol esters, and triglycerides and increased
      the expression of transforming growth factor-beta1 mRNA in liver tissue.
      Cholesterol-induced potentiation of the fibrogenic response is probably
      associated with transforming growth factor-beta1 induction due to accumulation of
      lipids and oxysterols in the liver.

PMID- 19110553
TI  - Myocardial resistance to ischemic and reperfusion injuries under conditions of
      chronic administration of opioid receptor agonists and antagonists.
AB  - Chronic treatment with opioid receptor ligands: nonselective peptide opioid
      receptor agonist dalargin (intraperitoneally in a dose of 1 mg/kg), selective
      nonpeptide kappa-receptor agonist GR 89696 (subcutaneously in a dose of 0.03
      mg/kg), nonselectrive nonpeptide antagonist quadazocine (subcutaneously in a dose
      of 3 mg/kg) or naltrexone (subcutaneously in a dose of 10 mg/kg) for 20 day had
      no effect of the incidence of ischemic ventricular arrhythmias and the size of
      necrotic zone after coronary occlusion and reperfusion in rats in vivo.

PMID- 19110554
TI  - Impairment of spermatogenesis in male rats during stress.
AB  - Stress is followed by severe disturbances in maturation of male gametes in the
      testicles, which concerns all populations of cells in the spermatogenic
      epithelium and modulates the function of endocrine cells (Leydig cells). The
      observed changes result in reproductive dysfunction of male albino rats.

PMID- 19110555
TI  - Role of CD38 in cell-cell interactions under conditions of endothelial
      dysfunction.
AB  - We studied the role of receptor/ectoenzyme CD38 in the formation of endothelial
      damage and pathogenesis of endothelial dysfunction. CD38 was located in sites of
      protrusion of the outer cytoplasmic membrane. The majority of CD38+ accumulation
      sites coincided with the protrusion pole, while in some cells expression of CD38
      was spread along the entire cell membrane surface or located on the pole opposite
      to the protrusion. We hypothesized that these states reflect the processes of
      rafting and clustering of the receptor, which are essential for cell-cell
      interactions in the pathogenesis of endothelial dysfunction.

PMID- 19110556
TI  - Role of opioid system in modulation of pain sensitivity under conditons of low
      and high environmental temperature.
AB  - The dependence of pain sensitivity in acetic acid-induced writhing test on
      environmental temperature was described by a bell-shaped curve. The maximum
      number of writhings was observed in thermoneutral environment and minimum in hot
      and cold environment. Under conditions of opioid receptor blockade with naloxone,
      naltrindole, norbinaltorphimine, analgesia is partially mediated by micro-, delta
      , and kappa-opioid receptors.

PMID- 19110557
TI  - Electron paramagnetic resonance study of nitric oxide production during 5-HT2
      receptor blockade in the blood, heart, and liver of rats with myocardial
      infarction.
AB  - The effect of serotonin 5-HT2 receptor blockade on nitric oxide production in
      rats with myocardial infarction was evaluated by the method of electron
      paramagnetic resonance. The spectra were recorded in samples of the heart tissue
      (left and right chambers), liver, and blood. 5-HT2 receptor blockade during
      myocardial infarction was followed by a decrease in the total content of nitrosyl
      complexes in the spin trap and R and T conformers of Hb-NO. The percent of T
      conformers increased in the remaining complexes of Hb-NO. These changes were
      observed in the heart and, particularly, in the blood. The amount of spin-trap
      complexes was lower in the liver. Hence, nitric oxide molecules were primarily
      associated with the spin trap in liver tissue. The decrease in the number of Hb
      NO complexes in the blood probably reflects the decrease in the severity of
      hypoxia due to myocardial infarction. A correlation was found between these
      changes and physiological state of rats. 5-HT2 receptor antagonist improved
      general state of rats with infarction and increased survival rate.

PMID- 19110558
TI  - Effect of spironolactone on hypertrophy of left ventricular myocardium in wistar
      rats with experimental uremia.
AB  - Chronic renal failure was modeled in rats by partial nephrectomy. Blood pressure,
      heart rate, concentrations of aldosterone, urea, creatinine, electrolytes, and
      protein, index of hypertrophy of visceral organs, and 24-h diuresis were
      evaluated. In rats treated with spironolactone, the index of myocardial
      hypertrophy did not considerably differ from that in sham-operated animals,
      whereas in untreated rats the test parameters considerably differ from the
      control. We concluded that the blockade of aldosterone receptors with
      spironolactone produced a cardioprotective effect in Wistar rats with subtotal
      nephrectomy.

PMID- 19110559
TI  - Effect of UV irradiation and magnetic field on immunometabolic effects of
      antibiotics immobilized in cell carriers.
AB  - The effects of UV and magnetic radiation on the immunometabolic activity of
      ampicillin and cephazolin immobilized in erythrocytic and leukocytic carriers
      were studied in intact Wistar rats and animals infected with staphylococci.
      Erythrocytic and leukocytic carriers with antibiotics were obtained. Injection of
      free antibiotics stimulated the immunosuppressive, pro-oxidant, and hepatotoxic
      effects, associated with staphylococcal infection. Treatment with antibiotics in
      erythrocytic and leukocytic carriers stimulated (to different degrees) the
      activity of the immune system and stabilized the parameters of LPO, antioxidant
      defense, cytolysis, and cholestasis. Ultraviolet irradiation and magnetic field
      modified (to different measures) the immunometabolic effects of ampicillin and
      cephazolin, immobilized in erythrocytic and leukocytic carriers, in animals with
      staphylococcal infection.

PMID- 19110560
TI  - Assessment of therapeutic drug efficiency.
AB  - The efficiency of drug therapy should be evaluated by not only its directed
      action on specific organ or target parameter, but also its effects on general
      regulatory and adaptive status.

PMID- 19110561
TI  - Effects of bioactive substances from tall delphinium on the development of acute
      inflammation of different genesis.
AB  - Effects of complex and individual bioactive substances extracted from tall
      delphinium on acute inflammation induced by carrageenin, acetic acid, serotonin,
      and histamine were studied. The studied plant substances produced a pronounced
      antiinflammatory effect comparable to that of nonsteroid antiinflammatory drugs.

PMID- 19110562
TI  - Combined blockade of AMPA and NMDA receptors in the brain of rats prevents
      pentylenetetrazole-induced clonic and tonic-clonic seizures without ataxia.
AB  - Intramuscular injection of selective NMDA receptor antagonists memantine and
      arcaine 4-fold decreased the incidence of pentylenetetrazole-induced generalized
      tonic-clonic seizures in rats, while the incidence of clonic seizures decreased
      by 1.2-1.3 times. Memantine and arcaine are characterized by low therapeutic
      index, i.e. induced ataxia in rats in doses exceeding the effective
      anticonvulsant dose by only 3.5-10 times. Intramuscular injection of IEM-1913
      (combined blockade of NMDA and AMPA receptors in the brain) decreased the
      incidence of pentylenetetrazole-induced clonic and tonic-clonic seizures in rats
      by 4-8 times. The therapeutic index of IEM-1913 surpassed that of memantine and
      arcaine by 200-600 times.

PMID- 19110563
TI  - Gastroprotective effect of nonstarch polysaccharide calcium pectate under
      experimental conditions.
AB  - Course prophylactic administration and single therapeutic treatment with calcium
      pectate improved resistance of rat gastroduodenal mucosa to ethanol-induced
      ulcers, prednisolone-induced ulcers, and H. Shay ulceration of the gastric
      mucosa.

PMID- 19110564
TI  - Anxiolytic and antidepressant characteristics of impaza.
AB  - Antibodies to endothelial NO synthase in ultralow doses exhibited anxiolytic and
      antidepressant effects and their efficiency after single and course treatment is
      not inferior to that of amitriptyline and diazepam. The psychotropic activity of
      ultralow-dose antibodies to endothelial NO-synthase is presumably one of
      important mechanisms of their efficiency in the treatment of erectile
      dysfunction.

PMID- 19110565
TI  - Neuroprotective activity of mexidole and 3-hydroxypyridine acetylcysteinate
      against the background of cerebral ischemia in the complex of experimental
      diabetes mellitus and exogenous hypercholesterolemia.
AB  - We studied the interaction of mexidol and 3-hydroxypyridine acetylcysteinate on
      the model of experimental ischemic stroke in rats. The preparations were
      effective in a dose 50 mg/kg (10-day treatment): they reduced the incidence of
      neurological disturbances (pareses, sensitivity disturbances) and improved
      antioxidant defense of the plasma.

PMID- 19110566
TI  - Ammonia potentiates the lethal effect of ethanol on rats.
AB  - Blood ammonia concentration increased in the portal vein (by 1.4 times) and
      inferior vena cava (caudal to the renal vein inflow, by 2.2 times; and cranial to
      the hepatic vein inflow, by 2.5 times) of rats 3 h after intragastric
      administration of 16.57 M ethanol solution (446 mmol/kg, approximately 1.4
      LD(50)/48 h). Ammonia concentration in mixed blood samples (post-decapitation)
      increased by 39%. The rate of ammonia accumulation was 3-fold higher in an
      intraperitoneal lavage solution. Three-hour exposure of ethanol-treated animals
      to atmospheric ammonia (0.84-1.07 mg/liter, i.e. approximately 1/8LC(50) for
      intact rats) was followed by a 2.4-fold increase in blood ammonia concentration
      as compared to specimens of the ethanol group. Ammonia inhalation potentiated the
      lethal effect of ethanol (dose variation factor 0.81), suppressed external
      respiration, and decreased oxygen consumption. Our results indicate that kinetic
      changes in endogenous ammonia have an adverse effect on the outcome of alcohol
      intoxication in rats.

PMID- 19110567
TI  - Vascular endothelial growth factor and its type 2 receptor in tumors and serum of
      patients with renal cancer.
AB  - It was found that renal cancer tissue is characterized by increased content of
      VEGF not depending on the parameters of normal tissue and expression of VEGFR2
      receptor. At the same time, the content of VEGFR2 in the tumor is determined by
      the state of the surrounding tissue and increases in low number of patients with
      tumors invading the renal capsule. Serum concentrations of VEGF and VEGFR2 in
      patients with renal cancer did not significantly differ from the corresponding
      values in the control group. No significant correlations between the levels of
      VEGF and VEGFR2 in the blood and tumor tissue were found.

PMID- 19110568
TI  - Protective effect of tripeptide in the presence of cyclophosphamide on the growth
      of cultured lymphoid tissue from rats of different age.
AB  - We studied the effect of tripeptide T-38 (Lys-Glu-Asp) in the presence of
      cyclophosphamide on cell proliferation and apoptosis in explants of splenic
      lymphoid tissue from young and old rats. Peptide T-38 in a concentration of 0.05
      ng/ml produced a stimulatory effect on the growth zone of the explants. Addition
      of 1 mg/ml cyclophosphamide to the culture medium suppressed cell proliferation,
      which was associated with enhanced expression of proapoptotic p53 protein. Under
      conditions of combined treatment with cyclophosphamide and T-38 no inhibiting
      effect of the cytostatics was observed. Thus, tripeptide T-38 in the presence of
      cytostatics produces a protective effect on cell proliferation in lymphoid tissue
      explants.

PMID- 19110569
TI  - Role of nitric oxide in the reaction of arterial vessels to laser irradiation.
AB  - Reactivity of arterial vessels in the small intestine mesentery to irradiation
      with a helium-neon laser before and after NO synthase blockade was studied by
      means of biomicroscopy. Blood flow velocity and vascular diameter increased under
      conditions of laser irradiation. During irradiation, arterial vasodilation was
      inversely related to the initial diameter. After treatment with NO synthase
      inhibitor, the dilatory response of vessels to laser irradiation was completely
      abolished (arteries, diameter >80 micro) or decreased by 2 times (arterioles,
      diameter <50 micro).

PMID- 19110571
TI  - Prospects of using titanium nickelide implants with modified surface in dental
      implantology.
AB  - Corrosion resistance and biocompatibility of 60 specimens of titanium nickelide
      with modified surfaces implanted into spongy bone were studied in rabbit
      experiments. Specimens modified by molybdenum ions exhibited high inertness and
      favorable tissue reaction. No accumulation of nickel and titanium ions in animal
      organs was detected.

PMID- 19110570
TI  - Effect of dehydration on morphogenesis of the lymphatic network and immune
      structures in the small intestine.
AB  - Dehydration was accompanied by cell changes in solitary lymphoid nodules and
      Peyer's patches. The proportion between lymphocytes, macrophages, and mast cells
      in lymphoid organs depended on the stage of dehydration. The inhibition of cell
      mitoses, disappearance of mature plasma cells and mast cells (per field of view),
      significant decrease in lymphocyte count, 4-5-fold increase in the number of
      destructive cells, and low density of cells and lymphatic network of the small
      intestine (per unit area) were observed on days 6 and 10 of dehydration. Severe
      morphological changes were also revealed in other layers of the small intestinal
      wall (mucosa, submucosa, lamina propria, etc.).

PMID- 19110572
TI  - Telecommunication monitoring is a method for studies of the effect of
      heliomagnetic fluctuations on cardiac function.
AB  - This paper presents the results of 9-year biogeophysical monitoring (1998-2007)
      of spatial and time effects of space weather and atmospheric and climatic factors
      on the status of normal subjects, which was carried out simultaneously in
      geographical areas situated at different latitudes. Requirements to conditions of
      long-term telecommunication biogeophysical monitoring studies are formulated,
      providing the reliability and reproducibility of the experiment results. The
      results indicate that the role of atmospheric and climatic factors in
      modification of dynamic regimens of human body functioning is significantly
      higher in subjects living at lower latitudes. The spatial and time regularities
      of the effects of space and physical factors on human body were detected (the
      latitude, time, trigger, amplitude, synergetic, and cumulative effects of the
      population averaging of the reaction). These effects indicate that human body
      belongs to a class of open nonlinear dynamic systems with all characteristics
      intrinsic of it.

PMID- 19110573
TI  - Evaluation of the number of ionogenic groups of inulinase by acid-base titration.
AB  - Acid base titration showed that Aspergillus awamori inulinase includes 178
      asparaginic and glutamic acid residues, 20 histidine, 10 serine, and 34 lysine
      and tyrosine residues. Denaturation temperature for this enzyme was calculated
      using analysis of the proportion of stabilizing and destabilizing amino acids in
      the molecule.

PMID- 19110574
TI  - Effect of atropine, propranolol, and atenolol on wave structure of heart rate
      oscillations in rats.
AB  - Were studied the effects of atropine and beta-adrenoblockers on the power of very
      low (<0.25 Hz), low (0.25-0.70 Hz), and high frequency (0.7-1.8 Hz) waves of the
      heart rhythm in wakeful rats. Atropine reduced the power of all waves in 100%
      cases. Propranolol on average decreased the power of very low frequency waves and
      increased the power of low and high frequency waves, although opposite effects
      were observed in many cases. Atenolol produced similar effects. Some animals
      demonstrated spontaneous moderation of respiratory rate to a level corresponding
      to low-frequency oscillations of the heart rhythm accompanied by elevation of the
      relative power of low frequency waves. Inconsistency of the effects of beta
      adrenoblockers in rats can be related to variability of sympathetic tone and
      spontaneous deceleration of respiration with the corresponding changes of low
      frequency waves. Augmentation of the high frequency waves during application of
      beta-adrenoblockers is not related to their action on CNS.

PMID- 19110575
TI  - Role of renin-angiotensin system in the formation of emotional state in humans.
AB  - We studied the effect of angiotensin-converting enzyme gene polymorphism on human
      emotional state in humans (189 athletes and 212 volunteers not engaged in sport
      activity). The distribution of angiotensin-converting enzyme genotypes was
      estimated. The dependence of aggression on age, sex, and professional activity
      was evaluated. This polymorphism was associated with physical aggression in
      female synchronized swimmers. Physical aggression in II genotype carriers was
      lower than in D allele carriers. Our results indicate that individual differences
      in aggression depend on professional activity and are genetically determined.

PMID- 19110576
TI  - Generation of excitatory postsynaptic potentials in the hippocampus after
      functional modification of glycosaminoglycans.
AB  - Experiments on hippocampal slices form 4-week-old rats (n=28) showed that
      addition of lidase (1.0 and 10.0 U/ml) to the perfusion solution (artificial
      cerebrospinal fluid) was accompanied by the impaired generation or blockade of
      excitatory postsynaptic potentials and population spikes in the hippocampal CA1
      region during stimulation of Schaffer collaterals. Removal of lidase from this
      solution normalized the amplitude of evoked responses. Hence, lidase in these
      concentrations produced a reversible effect on synaptic transmission. Our results
      indicate that structure and function of glycosaminoglycans in the extracellular
      matrix determine signal transduction in the nervous tissue.

PMID- 19110577
TI  - Effect of acoustic stimulation on GABAergic neurons in limbic structures of
      krushinskii-molodkina rats.
AB  - Quantitative study of GABAergic and main cells in the hippocampus and piriform
      cortex of Krushinskii-Molodkina rats was performed 1 month after the incidence of
      seizure activity evoked by acoustic stimulation. The number of neurons
      significantly decreased in both regions and, particularly, in the hippocampus and
      central area of the piriform cortex.

PMID- 19110578
TI  - Behavioral effect of terahertz waves in male mice.
AB  - We studied the effect of terahertz waves (3.6 THz, 81.5 micro, 15 mW) on the
      behavior of mice. The mice perceived terahertz waves even after short-term
      exposure (15 min). The effect of terahertz waves was maximum in direct contact of
      the mice with the laser. Increased anxiety of experimental animals was observed
      on the next day after 30-min irradiation.

PMID- 19110579
TI  - Role of central adrenergic structures in the regulation of granulocytopoiesis
      during cytostatic treatment.
AB  - We studied the role of central adrenergic structures in the regulation of
      granulocytic hemopoietic stem during cytostatic treatment. It was found that
      brain norepinephrine promoted the decrease in functional activity of adherent
      mononuclears of the hemopoiesis-inducing environment, cytokine-dependent and
      alpha-adrenergic mechanisms of regulation of division and maturation of
      granulomonocytic precursors under conditions of cyclophosphamide treatment. Under
      conditions of 5-fluorouracil treatment, the effect of the adrenergic system was
      aimed at the formation of granulocytic and fibroblast-type cell complexes,
      activation of the production of colony-forming activity by microenvironmental
      cells, and acceleration of maturation of neutrophilic granulocytes associated
      with the system of granulocytic CSF and peripheral alpha-adrenergic structures.

PMID- 19110580
TI  - Relationship between oxidized fibrinogen and hemostasis disturbances and
      endothelial dysfunction in myocardial infarction.
AB  - Oxidative modification of fibrinogen in acute myocardial infarction increased 1.3
      fold compared to that in CHD and 1.5-fold surpassed that in the control without
      CHD. Elevated content of oxidized fibrinogen correlated with increased levels of
      LPO products, von Willebrand factor, and fibrin degradation products, with
      accelerated leukocyte and platelet aggregation, and reduced content of NO
      metabolites in the plasma. Independent associations of oxidized fibrinogen with
      myocardial infarction and typical thrombogenic and hypercoagulation hemostasis
      disorders and endothelial dysfunctions were revealed.

PMID- 19110581
TI  - Specific function and morphology of the right ventricle of the heart during
      ischemic injury of the left ventricle.
AB  - Focal ischemia of the left ventricular myocardium was modeled by surgical
      ligation of the descending branch of the left coronary artery at the junction of
      the lower and middle thirds of this artery in anesthetized rabbits. Contractility
      and morphological characteristics of the right ventricular myocardium were
      evaluated 24, 72, and 120 h after treatment. Significant morphofunctional changes
      in the right ventricle manifested in the development of severe extracellular
      edema and increase in the area of damaged and destroyed myofibrils. However, the
      actual and maximum intraventricular pressure remained unchanged under these
      conditions. The degree of cardiomyocyte apoptosis increased on day 1, but
      returned to normal in the follow-up period. Our study demonstrated high
      sensitivity of the right ventricle to left ventricular dysfunction and early
      activation of compensatory mechanisms.

PMID- 19110582
TI  - Role of ATP-sensitive K(+)-channels in antiarrhythmic and cardioprotective action
      of adaptation to intermittent hypobaric hypoxia.
AB  - Mature Wistar rats were exposed to intermittent hypobaric hypoxia (5000 m, 6
      h/day, 30 sessions). This mode of adaptation enhanced heart tolerance to the
      arrhythmogenic action of 45-min coronary occlusion, but does not affect the
      infarction size/risk area ratio. In some series, the rats were exposed to more
      severe intermittent hypobaric hypoxia (7000 m, 8 h/day, 6 weeks) followed by 20
      min coronary occlusion and 3-h reperfusion one day after the last hypoxia
      session. In this case, adaptation reduced the infarction size/risk area ratio and
      enhanced cardiac tolerance to the arrhythmogenic effect of reperfusion, but had
      no effect on the incidence of ventricular arrhythmia during ischemia. We found
      that the cardioprotective and antiarrhythmic effects of adaptation to an altitude
      of 7000 m and the antiarrhythmic effect of 5000-m adaptation were mediated via
      activation of K(ATP) channels.

PMID- 19110583
TI  - Sex-related differences in the variability of vascular blood flow in middle-age
      individuals.
AB  - Analysis of spectral parameters of vascular blood flow variability revealed some
      sex-related peculiarities. The amplitude of aortic pulsation and total
      variability power of this parameter and its four components (ultralow frequency,
      very low frequency, low frequency, and high frequency range) were higher in
      women. The amplitude of microvascular pulsation and total variability power of
      this parameter and components were higher in men. In male patients, the relative
      variability power for the amplitude of microvascular pulsation was higher in the
      high frequency and low frequency ranges, but lower in the very low frequency and
      ultralow frequency ranges.

PMID- 19110584
TI  - Hydrophobic domains determine localization of IncC and IncG full-length proteins
      of C. trachomatis during their expression in cultured HeLa cells.
AB  - Plasmid vectors encoding hydrophilic (IncB, IncC, IncE, IncG) and hydrophobic
      (IncC, IncG) domains of C. trachomatis incorporation membrane proteins and
      reporter green fluorescing proteins were constructed. After transfection of HeLa
      cells with these plasmid constructs, localization of the complex proteins was
      determined by laser confocal microscopy. Tropism of hydrophobic domains to
      compartments constituting the exocytotic pathway in the cell was demonstrated.
      Location of signal/sorting sequences responsible for specific localization was
      determined.

PMID- 19110585
TI  - Modification and clearance of low density lipoproteins during the formation of
      endotoxin-lipoprotein complexes.
AB  - Changes in electrical charge and clearance rate of LDL after the formation of
      their complexes with bacterial LPS were studied in experiments on Wistar rats. It
      was found that binding of S. minnesota R595 LPS with (125)I-LDL sharply
      accelerated clearance of the greater part of LDL complexes, but on the other hand
      induced the appearance of an LDL-LPS subfraction with slower elimination rate
      compared to free LDL. Electrophoresis showed that after binding of LPS, LDL
      acquired a negative charge. These data suggest that the formation of LDL-LPS
      complexes is accompanied by modification of LDL due to which they acquire
      atherogenic properties.

PMID- 19110586
TI  - UHF-dielectrometry of the urine in prognosis of aggregation stability.
AB  - Dielectric permeability of the urine from healthy subjects and patients with
      various types of urolithiasis was studied using millimeter electromagnetic waves.
      The urine from healthy subjects and patients with urolithiasis differed in
      dielectric properties, specific water content, and structure of water. A
      relationship was revealed between aggregation stability of urine colloids and
      dielectric properties of the urine in millimeter-wave electromagnetic radiation.

PMID- 19110587
TI  - Effect of afobazole on teratogenic activity of cyclophosphamide in rats.
AB  - A new anxiolytic afobazole (1-100 mg/kg perorally, Russia) dose-dependently
      abolished the embryotoxic and teratogenic effects of cyclophosphamide and reduced
      the range of induced malformations in outbred albino rats. Our results suggest
      that afobazole possesses antiteratogenic activity.

PMID- 19110588
TI  - Excretion of afobazole and its metabolites with urine and feces in rats.
AB  - The amount of afobazole and identified metabolites was measured in the urine and
      feces of rats after intraperitoneal and peroral administration of the drug in a
      dose of 25 mg/kg. Over 1 day after intraperitoneal or peroral treatment with
      afobazole, urine and feces contained 0.1% initial compound (from administered
      dose) and 42.1% metabolites.

PMID- 19110589
TI  - Effect of liposomal tetracycline hydrochloride on enzymatic function of the
      liver.
AB  - Preparation and physicochemical properties of liposome-incorporated tetracycline
      are described. Comparison of the effects of tetracycline hydrochloride in free
      and liposome-incorporated forms on enzymatic functions of the liver showed that
      immobilization of the antibiotic into liposomes protects liver cells from
      functional disturbances.

PMID- 19110590
TI  - Antileprosy activity and preliminary toxicological characteristics of some
      dialkyldithiocarbamate derivatives.
AB  - Antileprosy activity of dialkyldithiocarbamate derivatives was studied in
      experiments on mice infected with M. leprae into paw pads. We found that 2
      diethyldithiocarbamoyl-3-cyano-5-nitropyridine is the most promising antileprosy
      agent; it effectively suppresses multiplication of M. leprae and is well
      tolerated under conditions of chronic animal experiment.

PMID- 19110591
TI  - Polyethylene glycol-conjugated immunoliposomes specific for olfactory ensheathing
      glial cells.
AB  - A novel immunoliposome delivery system was developed for directed transport into
      cultured olfactory epithelium cells. Monoclonal antibodies against glial
      fibrillary acidic protein (GFAP) served as a vector. Fluorescence microscopy
      showed that the target cells are specifically stained with Dil dye incorporated
      into liposomal membranes. This transport system holds promise for the delivery of
      bioactive substances to olfactory epithelial cells and modulation of their
      capacity to stimulate axonal regeneration.

PMID- 19110592
TI  - Evaluation of the Role of FMLF chemotaxic peptide receptors in umbilical cord
      blood granulocytes from newborns at risk of infectious inflammatory diseases.
AB  - We studied the role of receptors with high and low affinity for fMLF chemotaxic
      peptide in the generation of active oxygen species by umbilical cord blood
      granulocytes from newborns with normal neonatal period, born after normal or
      complicated gestation, in children with manifestations of bacterial infection
      born after complicated pregnancy, and in granulocytes of non-pregnant women with
      normal reproductive function. Granulocytes of children born after complicated
      pregnancy exhibited high reactivity in induction of respiratory burst in a wide
      range of fMLF concentrations. The presentation of receptors with high and low
      affinity on granulocytes during initiation of the respiratory burst differs in
      children born after complicated pregnancy and in healthy babies born after normal
      gestation. Presumably, the detected differences result from high expression of
      receptors with low affinity for fMLF and disorders or immaturity of mechanisms
      responsible for receptor inactivation.

PMID- 19110593
TI  - The Results of Mancini's test depend on the presence bound metal cations in the
      test protein.
AB  - Samples of human serum gamma-globulin with specifically bound copper or zinc
      cations were studied in Mancini's radial immunodiffusion test with human
      antibodies to IgG (H+L). The intensity of antibody binding to zinc-modified
      protein was 10-20% higher in comparison with the reference sample, while
      detection of gamma-globulin with bound copper by antibodies was 20-30% lower than
      in the corresponding reference sample. Comparison with the results of native
      gamma-globulin testing indicates limitations of Mancini's method as the
      quantitative assay for practical diagnosis, because under certain clinical
      conditions the traditional method can give over- and underestimated results.

PMID- 19110594
TI  - Effects of gram-positive microorganisms and their products on in vivo survival of
      hemopoietic clonogenic cells.
AB  - The effects of gram-positive bacterial strains (Lactobacillus acidophilus and
      Lactobacillus rhamnosus) and their subcellular components on the survival of
      hemopoietic clonogenic cells were evaluated by the formation of endogenous
      splenic colonies. The effects of these preparations on NO production were studied
      by the spin-trap paramagnetic resonance spectroscopy. Bacterial preparations from
      gram-positive bacteria stimulated survival of hemopoietic clonogenic cells, but
      did not induce NO production in contrast to E. coli LPS.

PMID- 19110595
TI  - Evaluation of antitumor activity of peptide extracts from medicinal plants on the
      model of transplanted breast cancer in CBRB-Rb(8.17)1Iem mice.
AB  - We studied antitumor effects of peptide extracts from plants on slowly growing
      mammary adenocarcinoma in CBRB-Rb(8.17)1Iem mice used as a model of breast cancer
      in humans. The antitumor effect of a single injection of the test peptides was
      evaluated by the delay of the appearance and growth of palpable breast cancer in
      mice over 4 weeks. Peptides from Hypericum perforatum and a mixture of
      Chelidonium majus L., Inula helenium L., Equisetum arvense L., and Inonotus
      obliquus exhibited maximum activity. Peptide extracts from Frangula alnuc Mill.
      and Laurus nobilis L. were less active. No antitumor effect of Camelia sinesis
      Kuntze was detected.

PMID- 19110596
TI  - Mechanisms of stimulation of granulocytopoiesis with neupogen in patients with
      breast cancer during chemotherapy.
AB  - The mechanisms of granulocytopoiesis stimulation with granulocytic CSF
      (neupogen), added to chemotherapy protocol (adriablastine+taxotere) in patients
      with stages III-IV breast cancer, were studied. The hemostimulatory effect of
      granulocytic CSF preparation is based on stimulation of proliferation and
      differentiation of granulomonocytopoisis precursor cell in the hemopoietic
      tissue, due to neupogen effects on hemopoietic elements and on the hemopoiesis
      inducing microenvironment cells.

PMID- 19110597
TI  - Geroprotective effect of ala-glu-asp-gly peptide in male rats exposed to
      different illumination regimens.
AB  - Exposure of male rats to permanent or natural illumination of North-Western
      Russia accelerated their death in comparison with animals exposed to standard (12
      h) light. Permanent illumination promoted the development of spontaneous tumors
      in comparison with the standard photoregimen. Injection of epithalone (synthetic
      Ala-Glu-Asp-Gly peptide; subcutaneously 0.1 microg/rat 5 times a week from the
      age of 4 months until natural death) virtually did not change the mean lifespan
      of male rats, but was associated with a significant (p<0.05) normalization of
      population aging rate and hence, time of mortality rate doubling in groups
      exposed to natural or constant illumination. Epithalone injected to rats exposed
      to any photoregimen significantly inhibited the development of spontaneous
      tumors, primarily testicular leydigomas and leukemias.

PMID- 19110598
TI  - Prediction of postinfarction remodeling of the left ventricle from parameters of
      tissue Doppler echocardiography.
AB  - The possibility of predicting undesirable postinfarction remodeling of the left
      ventricle from parameters of tissue doppler echocardiography was evaluated in 55
      patients with a history of acute myocardial infarction. Low diastolic rates of
      normal segments and the absence of the peak of isovolumetric contraction in the
      dysfunction zone were the most significant predictors of unfavorable remodeling.

PMID- 19110599
TI  - The significance of angiogenic growth factor in the pathogenesis of gestosis in
      pregnant women with varicose disease.
AB  - Recently, a close relationship between angiogenesis processes, growth factor
      activity in vascular abnormalities, and gestosis was revealed. In the present
      study, the dynamics of serum vascular endothelial growth factor during pregnancy
      was studied in patients with varicose disease with and without gestosis and in
      healthy women. The level of vascular endothelial growth factor increased during
      normal pregnancy, but decreased in gestosis. In pregnant patients with varicose
      disease, a less pronounced increase in this parameter was observed in comparison
      with that in healthy women.

PMID- 19110600
TI  - Gene therapy of amyotrophic lateral sclerosis.
AB  - Two-year experiments were performed to evaluate the neurotrophic effect of
      hypoxia-inducible factors (vascular endothelial growth factor and angiogenin)
      expressed in recombinant human adenoviruses in amyotrophic lateral sclerosis.
      Randomized placebo-controlled trial demonstrated safety and good tolerability of
      the recombinant antiviral drugs. The life span of patients under conditions of
      hypoxia increased after treatment with the test drug, which was probably related
      to improved resistance of motoneurons. The presence of virus-neutralizing
      antibodies decreases the effectiveness of adenoviral vectors, which necessitates
      differential approach to the selection of patients and continuous monitoring of
      gene therapy.

PMID- 19110601
TI  - Cardiomyocyte proliferation in rat fetuses under normal conditions and after
      heart injury.
AB  - Heart injury was inflicted to outbred albino rat fetuses on day 16 of prenatal
      development and cardiomyocyte proliferation was evaluated in the left ventricular
      zones adjacent to the wound and distant from it. The mitotic index of
      experimental animals was higher than in intact controls only for zones distant
      from the injury on day 10 after the intervention. The percentage of pathological
      metaphases gradually increased in all experimental groups, which causes doubt in
      the viability of postmitotic cardiomyocytes.

PMID- 19110602
TI  - Ultrastructural changes in the small intestine of suckling mice, caused by vibrio
      cholerae hemagglutinin/protease.
AB  - Suckling mice aged 4-5 days were injected with Vibrio cholerae
      hemagglutinin/protease and ultrastructural changes in their small intestine were
      studied after 5 h. The preparation caused a statistically significant
      accumulation of fluid in the intestine, appearance of large gaps along cell-cell
      spaces in the villi and crypts, intense production and secretion of the mucus by
      goblet cells. The formation of interepithelial cavities was paralleled by
      vascular changes, supplemented by extravasal disorders caused by mast cell
      reaction. The role of enterochromaffin cells and lipofibroblasts, modulating the
      secretion in the intestine, is confirmed.

PMID- 19110603
TI  - Stem cells of small intestinal epithelium.
AB  - Intestinal epithelium is a rapidly proliferating tissue and represents a unique
      model for the study of somatic stem cells. Here we summarized the data about
      markers, main properties, and methods of isolation of intestinal epithelial
      cells. Some aspects of molecular biology of the intestine are also discussed.

PMID- 19110604
TI  - In vitro study of matrix surface properties of porous granulated calcium
      phosphate ceramic materials made in Russia.
AB  - We performed in vitro screening of monophasic (hydroxyapatite, beta-tricalcium
      phosphate, carbonate-substituted hydroxyapatite with 0.59 and 5.9 wt%
      substitution with CO(3)(2-)) and biphasic (hydroxyapatite-tricalcium phosphate
      with various percentage of the components 80/20, 60/40, 20/80, silicon
      substituted hydroxyapatite with 0.79 wt% SiO(2)) porous granulated ceramics
      composed of calcium phosphate powders synthesized by methods of heterophasic
      interaction of reagents and precipitation from aqueous solutions using MTT test
      and cultured human fibroblasts. Acute toxicity of materials (24-h incubation with
      cell culture) and matrix properties (3, 5, 7, 14, 18, 21, 28 days in culture)
      were evaluated. We selected a batch of materials obtained by precipitation from
      aqueous solutions, which were non-toxic and were characterized by good matrix
      properties (for cells). Biphasic ceramics with hydroxyapatite-tricalcium
      phosphate ratio of 80/20 exhibited best characteristics, and ceramics on the
      basis of silicon-substituted hydroxyapatite showed moderate characteristics.

PMID- 19110605
TI  - Vital dye dil and fluorescent magnetic microparticles do not affect the phenotype
      of mesenchymal stem cells from human amnion and their differentiation capacity.
AB  - We present a method of labeling of mesenchymal stem cells from human amnion with
      a fluorescent dye Dil and microspheres (Bangs Laboratories). The possibility of
      administration of loaded cell culture was verified and comparative analysis of
      the phenotype of mesenchymal stem cells by the expression of fibronectin, nestin,
      CD13, CD29, CD34, CD44, CD54, CD90, CD105, CD106, HLA-ABC, HLA-DR, and PCNA was
      carried out. The labeled cells retained osteogenic differentiation capacity. The
      results suggest that fluorescent dye Dil and microspheres from Bangs Laboratories
      can be used for monitoring of mesenchymal stem cells from human amnion in in vivo
      experiments.

PMID- 19110606
TI  - Expression of intracellular molecular apoptosis regulator Bcl-2 in the liver in
      isolated and combined exposure to 24-h illumination and industrial frequency
      magnetic field.
AB  - We studied the effect of isolated and combined exposure to 24-h illumination and
      industrial frequency magnetic field on the expression of intracellular molecular
      apoptosis regulator Bcl-2 in the liver. Previous experiments showed enhanced
      expression of Bcl-2 protein in liver cells in animals maintained under conditions
      of 24-h illumination, whereas exposure to industrial frequency magnetic field had
      practically no effect on this process. Under conditions of combined exposure to
      24-h illumination and industrial frequency magnetic field, magnetic field
      partially suppressed the expression of Bcl-2 induced by 24-h illumination.

PMID- 19110607
TI  - Application of multipotent mesenchymal stromal cells from human adipose tissue
      for compensation of neurological deficiency induced by 3-nitropropionic Acid in
      rats.
AB  - We evaluated possible therapeutic effect of multipotent mesenchymal stromal cells
      from human adipose tissue differentiated to neuronal phenotype with retinoic acid
      on Wistar rats subjected to toxic effect of 3-nitropropionic acid.
      Transplantation of mesenchymal stromal cells from human adipose tissue
      considerably decreased neurological symptoms, normalized exploratory activity
      (open field test) and long-term memory (Morris test), which correlated with
      normalization of pathomorphological manifestations in the brain. Destructive
      changes in the caudate nucleus caused by treatment with 3-nitropropionic acid
      (reduced size of neurons, changes in their shape, and cell edema) tended to
      decrease under the effect of multipotent mesenchymal stromal cells: the area of
      neurons increased 2-fold, the cells acquired typical round shape, cell edema
      decreased.

PMID- 19110608
TI  - Effects of (60)co whole-body gamma-irradiation in different doses on the
      distribution of (188)Re-labeled autologous mesenchymal stem cells in wistar rats
      after intravenous (systemic) transplantation during different periods after
      exposure.
AB  - The effects of whole-body gamma-irradiation in different doses on the
      distribution of (188)Re-labeled mesenchymal stem cells obtained by culturing of
      the rat bone marrow cells were studied in different organs and tissues of animals
      after intravenous (systemic) injection. Irradiation stimulated homing of (188)Re
      labeled mesenchymal stem cells in organs and tissues of animals in comparison
      with this process in intact non-irradiated rats. The intensity of homing
      increased with increasing the irradiation dose and decreased with prolongation of
      the period between irradiation and systemic transplantation. It was hypothesized
      that increased migration of transplanted mesenchymal stem cells into irradiated
      organs and tissues can be caused by developing cell death processes. It seems
      that systemic transplantation of mesenchymal stem cells shortly after irradiation
      can be used for stimulation of reparative processes in damaged tissues.

PMID- 19110609
TI  - Development and introduction of production standards for cell products of
      mesenchymal origin.
AB  - The results of the development and introduction of universal production standards
      for cell products of mesenchymal origin are presented: technology for obtaining
      and culturing of primary cell cultures from human postnatal organs and tissues,
      cell product quality and safety control procedures, methods for cell product
      storage and transportation, and the necessary files.

PMID- 19110610
TI  - Effects of cytotoxins on intracellular na/K balance in mouse embryonic cell.
AB  - Cytoplasmic Na/K imbalance induced by cytotoxic substances (ethylene glycol and
      cytochalasin B) was studied. Incubation in Dulbecco's medium with these
      cytotoxins caused changes in K and Na concentrations in the mouse two-cell embryo
      blastomer. The effects of both substances resulted in a drop of Na content in the
      embryonic cell. Washing from cytochalasin B restored the initial Na/K balance in
      the cytoplasm. Possible adaptive mechanisms involved in the regulation of
      intracellular ionic homeostasis are discussed.

PMID- 19110611
TI  - Role of epidermal growth factor gene in the development of pancreatic cancer and
      efficiency of inhibitors of this gene in the treatment of pancreatic carcinoma.
AB  - The expression of epidermal growth factor receptors in normal and tumor cells of
      the pancreas, the type and incidence of EGFR gene polymorphism were studied. EGFR
      gene expression in pancreatic adenocarcinoma cells significantly surpassed that
      in normal pancreatic cells. On the other hand, AA genome and A allele
      polymorphism in the EGF gene nucleotide pair G-A 61 is a significant risk factor
      for pancreatic cancer. The effect of AG-1478 preparation (a new-generation
      inhibitor of EGFR) on apoptosis and cell proliferation in pancreatic cancer was
      evaluated. This preparation is not inferior to 5FU by its apoptotic effect and
      significantly reduces cell proliferation, its antiproliferative effect being 1.5
      times higher than that of 5FU.

PMID- 19110612
TI  - Endometrial mesenchymal stem cells isolated from the menstrual blood.
AB  - Stem cells from the endometrium isolated during menstrual bleeding were
      characterized. By their main surface markers, differentiation potential, and
      morphological signs these cells belong to mesenchymal stem cells. Specific
      features of this cell type are high clonogenic activity and low capacity to
      adipocyte differentiation.

PMID- 19110613
TI  - Stromal clonogenic precursors of hemopoietic microenvironment and their rank in
      the hierarchy of mesenchymal stem cells.
AB  - The hierarchy of stromal precursor cells was studied. Changes in the number of
      fibroblast CFU in foci forming in irradiated recipients were analyzed. These
      precursor cells are most close known descendants of mesenchymal stem cells, while
      inducible precursors rank lower in the hierarchy and are the cells directly
      enlarging the hemopoietic area in irradiated recipients.

PMID- 19110614
TI  - An evaluation of practice pattern for venous thromboembolism prevention in
      Lebanese hospitals.
AB  - BACKGROUND: Venous thromboembolism (VTE) is a major cause of death among
      hospitalized patients. Many VTE prophylaxis guidelines have been developed,
      including the American College of Chest Physicians (ACCP). VTE prophylaxis is
      required in specific patients; however, its practice is not always optimal, and
      often depends on the hospitals' protocols. In Lebanon, information about the
      appropriateness of VTE prophylaxis in health care centers is lacking. OBJECTIVE:
      The primary objective of this study was to evaluate the pattern of VTE
      prophylaxis application, including agents, doses, duration of treatment, and
      route of administration, in Lebanese health care centers. METHODS: A Lebanese
      multi-center, prospective, chart review study was conducted over 4 months. Data
      on demographics, VTE prophylaxis medication, dose, route, duration, and
      associated risk factors were collected by pharmacy students. The appropriateness
      of VTE prophylaxis was determined as per ACCP guidelines. Patients receiving VTE
      treatment were excluded from the study. Institutional review board (IRB) approval
      was obtained from each hospital center. RESULTS: A total of 840 patients were
      included. Both gender groups were equally represented in the sample and the mean
      age was 59 +/- 19.53 years. The majority (639/840, 76.1%) of the sample were at
      high risk for deep venous thrombosis (DVT), and inappropriate VTE prophylaxis was
      reported in 35% of the low-risk group, in 70% of the moderate-risk group, and in
      39% of the high-risk group (P < 0.0001). Comparing proper VTE prophylaxis
      practice between intensive care unit (ICU) and non-ICU patients, there was no
      statistical difference observed in teaching hospitals (67.2% vs. 65.5%, P =
      0.312). However, in non-teaching hospitals, appropriate VTE prophylaxis practice
      was more prevalent in ICU than non-ICU patients (65.9% vs. 51.2%, P = 0.004). The
      average duration of VTE prophylaxis was less than 10 days. Missing data was a
      major limitation for this study, where, for instance, the duration of prophylaxis
      could not be accurately abstracted in half of the sample. Another limitation was
      the absence of laboratory results needed for clinical assessment of the regimen
      used. CONCLUSION: This study reflected the importance of assessing VTE
      prophylaxis in Lebanese hospitals, thus, the need for implementing established
      guidelines to improve the overall patient safety.

PMID- 19110615
TI  - Immunomagnetic enrichment of human and mouse hematopoietic stem cells for gene
      therapy applications.
AB  - The hematopoietic stem cells (HSCs) constitute an ideal target for the gene
      therapy of inherited diseases affecting the hematopoietic system. HSCs, however,
      constitute a very rare population of progenitor cells, most of which are out of
      cycle in normal bone marrow. To facilitate their transduction with gammaretro
      viral or lentiviral vectors, HSCs are generally enriched using physical or
      pharmacologic methods. In this chapter we describe efficient procedures which are
      frequently used to enrich human and mouse HSCs, aiming at the transduction of
      these cells with adequate gene therapy vectors or the subsequent purification of
      particular HSCs by fluorescence-activated cell sorting.

PMID- 19110616
TI  - Isolation of human and mouse hematopoietic stem cells.
AB  - Hematopoietic stem cells (HSC) are rare with estimated frequencies of 1 in 10,000
      bone marrow cells and 1 in every 100,000 blood cells. The most important
      characteristic of HSC is their capacity to provide complete restoration of all
      blood cell lineages after bone marrow ablation. Therefore they are considered as
      the ideal targets for various clinical applications including stem cell
      transplantation and gene therapy. In adult mice and men, the main stem cell
      source is the bone marrow. For clinical applications HSC derived from umbilical
      cord blood (UCB) and G-CSF mobilized peripheral blood (PB) have been demonstrated
      to have several advantages compared to bone marrow; therefore, they are slowly
      replacing BM as alternative source of stem cells. The mouse is the model organism
      of choice for immunological and hematological research; therefore, studies of
      murine HSC are an important research topic. Here we described the most often used
      protocols and methods to isolate human and mouse HSC to high purity.

PMID- 19110617
TI  - Murine hematopoietic stem cell transduction using retroviral vectors.
AB  - Hematopoietic stem cells (HSCs) represent an important target cell population in
      bone marrow transplantation and gene therapy applications. Their progeny cells
      carry the genetic information of the HSCs and replenish the blood and immune
      system. Therefore, in the setting of inherited diseases, transduction of HSCs
      with retroviral vectors (including gammaretro- and lentiviral vectors) offers the
      possibility to correct the phenotype in all blood lineages as demonstrated in
      clinical trials for immunodeficiencies (e.g., X-SCID). In the process of
      developing gene therapy strategies for patient applications, suitable mouse
      models for the human gene therapy are important to validate the concept. Stem
      cell-enriched populations such as lineage negative cells as the functional
      equivalent of human CD34(+) cells can be isolated from murine bone marrow and
      efficiently transduced using retroviral vectors. This chapter provides a step-by
      step protocol for retroviral transduction of murine lineage negative cells.

PMID- 19110619
TI  - Short-term culture of human CD34+ cells for lentiviral gene transfer.
AB  - Haematopoietic Stem Cells (HSCs) are attractive targets for the gene therapy.
      Upon ex vivo gene transfer and transplant, they may generate a progeny of gene
      corrected cells potentially for a lifespan. The viral vectors most often used for
      HSC gene transfer are gamma-retroviral vectors (RVs) and HIV-derived lentiviral
      vectors (LVs). LVs have been proposed as improved tools for this task because
      they are able to transduce non-proliferating cells, while RVs are not. This
      implies that HSCs, which are mainly quiescent cells, need to be induced to
      proliferate in order to be transduced by RVs, whereas a prolonged stimulation is
      not needed for transduction by LVs. A short in vitro manipulation should reduce
      the risk of altering the characteristic biological properties of HSCs.We describe
      here methods for short-term ex vivo culture and gene transfer into human HSCs.
      Cord blood-derived HSC gene transfer can be tuned to limit the average level of
      vector integration or instead to maximize the frequency of transduction and
      extent of transgene expression, according to the absence or presence of
      cytokines. Mobilized peripheral blood-derived HSCs need cytokine stimulation to
      maintain viability and obtain adequate levels of gene transfer. Although HSCs can
      be transduced by LVs in short ex vivo culture, they display low permissiveness to
      the vector. Recently, we have demonstrated that this is because proteasome
      activity restricts LV gene transfer in HSCs. We developed and describe here
      strategies that effectively overcome this restriction. Finally, we also provide
      methods for the assessment of the transduction efficiency.

PMID- 19110618
TI  - Genetic modification of human hematopoietic cells: preclinical optimization of
      oncoretroviral-mediated gene transfer for clinical trials.
AB  - This chapter provides information about the oncoretroviral transduction of human
      hematopoietic stem/ progenitor cells under clinically applicable conditions. We
      describe in detail a short -60 h transduction protocol which consistently yields
      transduction efficiencies in the range of 30-50% with five different
      oncoretroviral vectors. We discuss a number of parameters that affect
      transduction efficiency, including the oncoretroviral vector characteristics, the
      vector stock collection, the source of CD34+ cells and transduction conditions.

PMID- 19110620
TI  - T cell culture for gammaretroviral transfer.
AB  - Gene transfer into mature T cells with gammaretroviral vectors requires
      prestimulation, as only mitotic cells are susceptible to integration of the
      gammaretroviral proviral genome. Costimulation via the CD3/ TCR complex and a
      second costimulatory molecule, such as CD28 was found to better preserve
      functionality of the T lymphocytes during ex vivo expansion than stimulation with
      anti-CD3 alone. The protocols described here for prestimulation and transduction
      of human and murine T cells with gammaretroviral vectors were optimized for high
      level gene transfer and maximum yield of functional T lymphocytes.

PMID- 19110621
TI  - Retroviral transduction of murine primary T lymphocytes.
AB  - In comparison to human T cells, efficient retroviral gene transfer and subsequent
      expansion of murine primary T cells is more difficult to achieve. Herein, we
      describe an optimized gene transfer protocol utilizing an ecotropic viral vector
      to transduce primary murine T cells activated with magnetic beads coated with
      agonistic anti-CD3 and CD28 antibodies. Activated T cells are subsequently
      centrifuged (spinoculated) on RetroNectin-coated tissue culture plates in the
      context of retroviral supernatant. Variables found to be critical to high gene
      transfer and subsequent efficient T cell expansion included CD3/CD28 magnetic
      bead to cell ratio, time from T cell activation to initial spinoculation,
      frequency of T cell spin-oculation, interleukin-2 concentration in the medium,
      and the initial purity of the T cell preparation.

PMID- 19110622
TI  - Lentiviral vector gene transfer into human T cells.
AB  - Efficient gene transfer into T lymphocytes may allow the treatment of several
      genetic dysfunctions of the hematopoietic system, such as severe combined
      immunodeficiency, and the development of novel therapeutic strategies for
      diseases such as cancers and acquired diseases such as AIDS. Lentiviral vectors
      can transduce many types of nonproliferating cells, with the exception of some
      particular quiescent cell types such as resting T cells. Completion of reverse
      transcription, nuclear import, and subsequent integration of the lentivirus
      genome do not occur in these cells unless they are activated via the T-cell
      receptor (TCR) and/or by cytokines inducing resting T cells to enter in G(1b)
      phase of the cell cycle. In T-cell-based gene therapy trials performed to date,
      cells have been preactivated via their cognate antigen receptor (TCR). However,
      TCR stimulation shifts the T cells from naive to memory phenotype and leads to
      skewing of the T-cell population. Since, especially the naive T cells will
      provide a long-lasting immune reconstitution to patients these are the cells that
      need to be transduced for effective gene therapy. Now it is clear that use of the
      survival cytokines, IL-2 or IL-7, allows an efficient lentiviral vector gene
      transfer and could preserve a functional T-cell repertoire while maintaining an
      appropriate proportion of naive and memory T cells. In this protocol we give
      details on lentiviral transduction of T cells using TCR-stimulation or rIL-7
      prestimulation. In addition, we describe the use of a new generation of
      lentiviral vectors displaying T-cell-activating ligands at their surface for
      targeted T-cell gene transfer.

PMID- 19110623
TI  - DNA transposons for modification of human primary T lymphocytes.
AB  - Genetic modification of peripheral blood T lymphocytes (PBL) or hematopoietic
      stem cells (HSC) has been shown to be promising in the treatment of cancer (Nat
      Rev Cancer 3:35-45, 2003), transplant complications (Curr Opin Hematol 5:478-482,
      1998), viral infections (Science 285:546-551, 1999), and immunodeficiencies (Nat
      Rev Immunol 2:615-621, 2002). There are also significant implications for the
      study of T cell biology (J Exp Med 191:2031-2037, 2000). Currently, there are
      three types of vectors that are commonly used for introducing genes into human
      primary T cells: oncoretroviral vectors, lentiviral vectors, and naked DNA.
      Oncoretroviral vectors transduce and integrate only in dividing cells. However,
      it has been shown that extended ex vivo culture, required by oncoretroviral
      mediated gene transfer, may alter the biologic properties of T cells (Nat Med
      4:775-780, 1998; Int Immunol 9:1073- 1083, 1997; Hum Gene Ther 11:1151-1164,
      2001; Blood 15:1165-1173, 2002; Proc Natl Acad Sci U S A, 1994). HIV-1-derived
      lentiviral vectors have been shown to transduce a variety of slowly dividing or
      nondividing cells, including unstimulated T lymphocytes (Blood 96:1309-1316,
      2000; Gene Ther 7:596-604, 2000; Blood 101:2167-2174, 2002; Hum Gene Ther 14:1089
      1105, 2003). However, achieving effective gene transfer and expression using
      lentivirus vectors can be complex, and there is at least a perceived risk
      associated with clinical application of a vector based on a human pathogen (i.e.,
      HIV-1). Recently it has been found that oncoretroviral and lentiviral vectors
      show a preference for integration into regulatory sequences and active genes,
      respectively (Cell 110:521-529, 2002; Science 300:1749-1751, 2003). Additionally,
      insertional mutagenesis has become a serious concern, after several patients
      treated with an oncoretroviral vector for X-linked SCID developed a leukemia-like
      syndrome associated with activation of the LMO2 oncogene (Science 302:415-419,
      2003). Naked DNA-based genetic engineering of human T lymphocytes also requires T
      cells to be activated prior to gene transfer (Mol Ther 1:49-55, 2000; Blood
      101:1637-1644, 2003; Blood 107:2643-2652, 2006). In addition, random integration
      by electroporation is of low efficiency. We have recently reported that the
      Sleeping Beauty transposon system can efficiently mediate stable transgene
      expression in human primary T cells without prior T cell activation (Blood
      107:483-491, 2006). This chapter describes methodology for the introduction of SB
      transposons into human T cell cultures with subsequent integration and stable
      long-term expression at noticeably high efficiency for a nonviral gene transfer
      system.

PMID- 19110624
TI  - Retroviral gene transfer into primary human natural killer cells.
AB  - Modulation of intracellular signaling pathways or receptor expression in natural
      killer (NK) cells by genetic manipulation is an attractive possibility in studies
      of NK cell specificity and function. Moreover, feasible applications of these
      genetic manipulations in the context of gene and NK cell therapy regimens may be
      considered. However, efficient gene modification of primary NK cells has been
      largely hampered by the absence of an efficient gene-transfer protocol.A
      retrovirus-based easy-to-use transduction protocol that can insert the gene of
      interest permanently into primary NK cells would be an important tool to advance
      our studies in NK cell biology and NK cell-mediated therapies. We have recently
      described a protocol for efficient expansion of NK cells under good manufacturing
      practice (GMP) conditions from the healthy donors and from patients with
      hematological malignancies. As the active division of cells is a prerequisite for
      efficient retroviral insertion, the high rate of expansion in this protocol
      provides more efficient transduction by retroviral vectors. We hereby present
      this simple and efficient retroviral vector-based gene-transfer protocol for such
      ex vivo cultured primary human NK cells.

PMID- 19110625
TI  - Lentiviral vector-mediated genetic programming of mouse and human dendritic
      cells.
AB  - Dendritic cells (DCs) play a key role in the orchestration of immune reactions.
      Manipulation of DC function through genetic manipulation for vaccine development
      provides a multitude of applications for active immunotherapy of cancer and
      chronic infections. Several laboratories have shown that lentiviral vectors (LVs)
      are efficient and consistent tools for ex vivo gene manipulation of DCs and their
      precursors. LVs integrate in the genome of target cells resulting in persistent
      and stable transgene expression, and gene delivery does not result in cytostatic
      or nonspecific adverse immunomodulatory reactions. Mouse, macaque, and human DCs
      are efficiently transduced with LVs, allowing preclinical vaccination studies to
      be gradually implemented into clinical trials. This chapter describes HIV-1
      derived LV transduction used for ex vivo gene delivery of marking genes,
      antigens, and immunomodulatory molecules into mouse and human hematopoietic
      precursors and DCs. With the perspective of bioengineering DCs from the inside
      out, we also describe a one-hit LV transduction method for constitutive
      expression of GM-CSF and IL-4 genes, which allows self-differentiation of mouse
      and human hematopoietic precursor cells into highly viable and potent DCs.

PMID- 19110626
TI  - In situ (in vivo) gene transfer into murine bone marrow stem cells.
AB  - Adult bone marrow stem cell is an ideal target for gene therapy of genetic
      diseases, selected malignant diseases, and AIDS. The in vivo approach of
      lentivirus vector (LV)-mediated stem cell gene transfer by intrafemoral (IF)
      injection can take full advantage of any source of stem cells residing in the
      bone cavity. Such an approach may avoid several difficulties encountered by ex
      vivo hematopoietic stem cell (HSC) gene transfer. We have shown that both HSC and
      mesenchymal stem/progenitor cells (MSC) can be genetically modified successfully
      by a single "in situ" IF injection in their natural "niche" in mice without any
      preconditioning. This approach may provide a novel application for treatment of
      human diseases, and represent an interesting new tool to study adult stem cell
      plasticity and the nature of unperturbed hematopoiesis.

PMID- 19110627
TI  - In vivo and ex vivo gene transfer in thymocytes and thymocyte precursors.
AB  - The thymus provides a specialized environment allowing the differentiation of T
      lymphocytes from bone marrow-derived progenitor cells. We and others have
      demonstrated that gene transfer into distinct thymocyte populations can be
      obtained, both in vivo and ex vivo, using lentiviral vectors. Here, we describe
      techniques for intrathymic lentiviral transduction in mice, using a surgical
      approach wherein the thoracic cavity is exposed as well as a significantly less
      invasive strategy wherein virions are directly injected through the skin.
      Moreover, thymocyte differentiation from murine and human progenitors is now
      feasible in vitro, under conditions wherein the Notch and IL-7 signaling pathways
      are activated. We describe methods allowing transduction of murine and human
      progenitors and their subsequent differentiation into more mature thymocytes.
      Conditions for lentiviral gene transfer into more differentiated human thymocyte
      subsets are also presented. Optimization of technologies for HIV-based gene
      transfer into murine and human thymocyte progenitors will advance strategies
      aimed at modulating T-cell differentiation and function in-vivo; approaches
      potentially targeting patients with genetic and acquired immunodeficiencies as
      well as immune-sensitive tumors. Furthermore, this technology will foster the
      progression of basic research aimed at elucidating molecular aspects of T-cell
      differentiation in mice and humans.

PMID- 19110628
TI  - Design and production of retro- and lentiviral vectors for gene expression in
      hematopoietic cells.
AB  - Successful retroviral gene transfer into hematopoietic cells has been
      demonstrated in a number of small and large animal models and clinical trials.
      However, severe adverse events related to insertional muta-genesis in a recent
      clinical trial for X-linked severe combined immunodeficiency reinforced the need
      to develop novel retroviral vectors with improved biosafety. Improvements include
      the use of self-inactivating (SIN) vectors as well as improvements in vector
      design. This chapter describes the basic design of gamma-retroviral and
      lentiviral SIN vectors that utilize a split-packaging system and includes a
      description of the various cloning modules frequently used in the design of such
      vectors that impact biosafety, titer, and transgene expression. In addition, this
      chapter describes the methods used for high titer vector production using calcium
      phosphate transfection both at research scale and at large scale for clinical
      application using a closed system bioreactor.

PMID- 19110629
TI  - Knock-down of gene expression in hematopoietic cells.
AB  - RNA interference (RNAi) is an evolutionarily conserved sequence-specific post
      transcriptional gene silencing mechanism triggered by double-stranded RNA (dsRNA)
      that results either in degradation of homologues mRNAs or inhibition of mRNA
      translation. The effector molecules which activate the RNAi pathway are small
      regulatory RNAs including small interfering RNAs (siRNAs) which are processed
      from longer dsRNAs by the RNAse III enzyme Dicer, and microRNAs (miRNAs)
      generated in a regulated multistep process from endogenous primary transcripts
      (pri-miRNA). Since, in principle, any gene can be silenced, RNAi provides a
      powerful tool to investigate gene function, and it is therefore a widely used
      gene silencing method in functional genomics. This chapter provides a collection
      of protocols for specific gene knock-down in hematopoietic cells by the
      application of short-hairpin RNAs (shRNAs) transcribed by RNA polymerase III (pol
      III) promoters or artificial-miRNAs (art-miRNAs) expressed from RNA pol II
      promoters using lentiviral vectors, respectively.

PMID- 19110630
TI  - The use of retroviral vectors for tet-regulated gene expression in cell
      populations.
AB  - Today the treatment of inherited diseases holds a major field in gene therapy,
      and gamma -retroviral vectors are often the preferred tool for stable
      introduction of the therapeutic gene(s) into the host cell genome. In many cases,
      the newly introduced gene has to be constitutively expressed, since enzyme
      function often is required at all times. However, in some cases gene function
      might be demanded only transiently, making a strict control of gene expression
      necessary. For more than a decade, the tet-system has proven to facilitate such
      strict control by tightly regulating gene expression, thereby assuring high
      expression levels in almost all organs and tissues. Yet, most of these results
      were obtained from the analysis of either selected cell clones or transgenic
      animals. On the contrary, in case of conditional gene expression, as necessary
      for gene therapy approaches, the use of genetically modified cell populations,
      where the majority of cells display similar regulatory properties, is required.
      Therefore, great effort has been undertaken to design viral vectors carrying the
      response unit that enables homogenous regulation of gene expression in transduced
      cell populations. This article summarizes critical points that have to be
      considered for the conditional regulation of gene expression in cell populations
      mediated by the tet-system. Examples of the required vector elements and tet
      system components as well as advice on the handling of the system are given.
      These tools have been specifically developed to improve population-based gene
      regulation.

PMID- 19110631
TI  - Detection of replication competent retrovirus and lentivirus.
AB  - Retroviral vectors based on murine leukemia viruses (MuLV) have been used in
      clinical investigations for over a decade. Alternative retroviruses, most notably
      vectors based on HIV-1 and other lentiviruses, are now entering into clinical
      trials. Although vectors are designed to be replication defective, recombination
      events during vector production could lead to the generation of replication
      competent retroviruses (RCR) or replication competent lentiviruses (RCL). Careful
      screening of vector prior to human use must insure that patients are not
      inadvertently exposed to RCR or RCL. We describe methods capable of detecting low
      levels of virus contamination and discuss the current regulatory guidelines for
      screening gene therapy products intended for human use.

PMID- 19110632
TI  - Release testing of retroviral vectors and gene-modified cells.
AB  - This chapter will review the design and execution of release testing requirements
      for retroviral vectors and gene-modified cells consistent with ensuring the
      success of the clinical trial on the basis of current US regulatory requirements.
      It is the ethical and legal responsibility of the clinical trial sponsor(s) to
      ensure safety of the patients through proper evaluation of the drug products
      prior to use. Any clinical trial drug product used in human subjects must be
      produced and evaluated for safety, quality, purity, and effectiveness according
      to Current Good Manufacturing Practices appropriate for the stage of clinical
      development.

PMID- 19110633
TI  - Copy number determination of genetically-modified hematopoietic stem cells.
AB  - Human gene transfer with gammaretroviral, murine leukemia virus (MLV) based
      vectors has been shown to effectively insert and express transgene sequences at a
      level of therapeutic benefit. However, there are numerous reports of disruption
      of the normal cellular processes caused by the viral insertion, even of
      replication deficient gammaretroviral vectors. Current gammaretroviral and
      lentiviral vectors do not control the site of insertion into the genome, hence,
      the possibility of disruption of the target cell genome. Risk related to viral
      insertions is linked to the number of insertions of the transgene into the
      cellular DNA, as has been demonstrated for replication competent and replication
      deficient retroviruses in experiments. At high number of insertions per cell,
      cell transformation due to vector induced activation of proto-oncogenes is more
      likely to occur, in particular since more than one transforming event is needed
      for oncogenesis. Thus, determination of the vector copy number in bulk transduced
      populations, individual colony forming units, and tissue from the recipient of
      the transduced cells is an increasingly important safety assay and has become a
      standard, though not straightforward assay, since the inception of quantitative
      PCR.

PMID- 19110634
TI  - Tissue procurement for molecular studies using laser-assisted microdissection.
AB  - Properly collected and stored human specimens offer the unique opportunity to
      study human diseases at the molecular level in the real in vivo situation. The
      intention of this chapter is, first, to raise the awareness for important points,
      which have to be clarified before human tissue samples are collected and stored
      for molecular studies. Second, detailed protocols are provided for the fixation
      and processing of bone marrow trephines and the isolation of morphologically and
      immunohistochemically defined pure cell populations from bone marrow trephine
      sections using laser-assisted microdissection.

PMID- 19110635
TI  - Leukemia diagnosis in murine bone marrow transplantation models.
AB  - The mouse is the most commonly used experimental animal, and a wide range of
      tumor types can arise in their hematopoietic system. Therefore, for research
      scientists and graduate students working in the field of experimental hematology,
      immunology, and cancer research, there is an urgent need for well-established
      protocols for the preparation of histology and cytology for leukemia diagnosis.
      Moreover, the criteria for the classification of hematopoietic neoplasms often
      vary between different laboratories. In this chapter, we describe diagnosis and
      analysis of leukemia in murine bone marrow transplantation models based primarily
      on the findings of the histology and cytology of hematopoietic and infiltrated
      tissues, peripheral blood smear, and immunophenotyping by FACS analysis.

PMID- 19110636
TI  - Humanized mouse models to study the human haematopoietic stem cell compartment.
AB  - The ideal way to assess hematopoietic stem cells is to observe their growth in
      the endogenous microenvironment where they would receive the appropriate signals.
      With colonies of inbred mice, it is possible to myeloablate recipients and
      transplant hematopoietic cells from genetically similar mice and observe the
      growth of primitive hematopoietic cells in their endogenous environment for a
      significant proportion (10 months) of an organisms lifespan (29 months average).
      It is not possible to perform these experiments in humans, but
      xenotransplantation mouse models provide the closest paradigm for the human
      hematopoietic environment at the present time.

PMID- 19110637
TI  - Canine models of gene-modified hematopoiesis.
AB  - Large animal models have played a crucial role in the development of gene therapy
      protocols. A significant advantage of large animal models over rodent models
      includes the ability to more easily translate protocols developed in large
      animals to humans. For gene therapy applications, nonhuman primates and canines
      have been the main large animal models. Canines have the advantage that there are
      disease models available, e.g., hemolytic anemia (pyruvate kinase deficiency),
      leukocyte adhesion deficiency, severe combined immunodeficiency (XSCID), storage
      diseases, and others. In addition, all three major integrating virus systems,
      i.e., gammaretrovirus-, HIV-derived lenti- and foamy virus vectors are able to
      efficiently transduce canine hematopoietic cells. Here we describe protocols
      developed for efficient transduction of canine hematopoietic repopulating cells.

PMID- 19110638
TI  - Detection of retroviral integration sites by linear amplification-mediated PCR
      and tracking of individual integration clones in different samples.
AB  - In order to restore or to introduce a gene function integrating viral vector
      systems are used to genetically modify hematopoietic stem cells. The occurrence
      of immortalized cell clones after transduction in vitro (Blood 106:3932-3939,
      2005) and clonal dominance as well as leukemia in preclinical (Nat. Med. 12:401-
      409, 2006; Blood 106:2530-2533, 2005; Science 308:1171-1174, 2005; Science
      296:497, 2002; Blood 107:3865-3867, 2006) and clinical (Nat. Med. 12:401-409,
      2006; Science 302:415-419, 2003; J. Clin. Invest. 118:3143-3150, 2008) gene
      therapy trials revealed that the nondirected integration of a vector may be
      associated with serious side effects. By means of the linear amplification
      mediated PCR (LAM-PCR) (Blood 100:2737-2743, 2002; Nat. Methods 4:1051-1057,
      2007) it is possible to identify miscellaneous vector-genome junctions in one
      sample, each unique for one integration clone down to the single cell level. Thus
      this method allows to determine the clonality of a genetically modified
      hematopoietic repopulation as well as to sequence the vector integration sites
      and therefore to analyze the integration site distribution and the influence of
      the vector integration site on the cell fate. The recognition of the integration
      site sequence corresponding to a specific clone allows the tracking of an
      individual clone in various samples.

PMID- 19110639
TI  - Retroviral insertion site analysis in dominant haematopoietic clones.
AB  - Identification of retroviral vector insertion sites in single, dominating cell
      clones has become an important tool for the investigation of cellular signalling
      pathways involved in clonal expansion and malignant transformation. Also, recent
      severe adverse events in clinical trials resulting from retroviral vector
      mediated insertional mutagenesis underline the need of well-designed safety
      studies including integration site analyses to estimate cost/benefit ratios in
      gene therapy. We have recently described a modified ligation-mediated PCR (LM
      PCR) method allowing preferential retrieval of insertion sites causally linked to
      clonal dominance of an affected clone. In the first part of the given work we
      focus on particularities of the LM PCR procedure to be taken into account when
      working with self-inactivating as compared to 'classical' retrovectors. In the
      following sections we focus on data acquisition, processing, organisation, and
      analysis. Thus the protocol presented here should be helpful in establishing and
      utilising databases of retroviral integration sites.

PMID- 19110640
TI  - Tracking gene-modified T cells in vivo.
AB  - Identification, monitoring, and analysis of genetically modified cells in the
      peripheral blood are an important component of the clinical follow-up of patients
      treated by hematopoietic cell gene therapy. Analysis of gene-marked peripheral
      blood cells provides crucial information on gene transfer efficiency as well as
      on the nature and characteristics of the genetically modified cells, and may
      provide early evidence of the occurrence of potentially detrimental side effects.
      T lymphocytes are a convenient target for this type of analysis, due to their
      abundance and their relatively long life span in vivo. Tracking of gene-marked T
      cells is based on relatively simple, FACS- and PCR-based techniques, which may be
      applied to monitoring genetically modified T cells as well as T cells derived
      from transplanted, genetically modified hematopoietic stem cells. This chapter
      provides a description of these techniques and clues to their rational use in a
      clinical setting.

PMID- 19110641
TI  - DNA microarray studies of hematopoietic subpopulations.
AB  - In recent years, one of the most quickly incorporated methods in biomedical
      research has been microarray technology. Microarrays have been designed for the
      purpose of genotyping (e.g., SNP analysis), expression analysis (mRNA, miRNA,
      exon arrays), chromatin immunoprecipitations (ChIP-on-chip technology), and DNA
      sequencing. In this chapter we will focus on the application of DNA microarrays
      in gene expression analysis of mRNA. This technology allows for the simultaneous
      analysis of transcription patterns of literally thousands of genes, making it a
      very powerful approach. Hematopoietic sub-populations are relatively easy to
      obtain by using fluorescence-activated cell sorting or magnetic bead cell
      separation. Over the last decade, the combination of these purification
      techniques with microarray analysis has resulted in an enormous gain of knowledge
      of blood lineages and their development.

PMID- 19110642
TI  - Quantification of genomic mutations in murine hematopoietic cells.
AB  - Maintaining the stability of the genome is critical to cell survival and normal
      cell growth. Genetic modification of hematopoietic cells might bear an inherent
      increased risk for the accumulation of DNA mutations. It frequently requires
      cultivation of the cells under super-physiological oxygen levels, which can
      result in increased oxidative damage, as well as under super-physiological
      concentrations of cytokines, which might interfere with DNA-damage checkpoint
      activation and by this means might result in an increased mutational load. We
      describe here a protocol for monitoring the frequency of DNA mutations in bone
      marrow cells post transduction or upon selection either in vitro or in vivo based
      on the lacZ-plasmid (pUR288) transgenic mouse (small blue mouse) mutation
      indicator strain.

PMID- 19110643
TI  - Proteomics studies after hematopoietic stem cell transplantation.
AB  - Complex biological samples hold significant information on the health status and
      on development of disease. Approximately 35,000 human genes give rise to more
      than 1,000,000 functional entities at the protein level. Thus, the proteome
      provides a much richer source of information than the genome for describing the
      state of health or disease of humans. The composition body fluids comprise a rich
      source of information on changes of protein and peptide expression. Here we
      describe the application of capillary electrophoresis (CE) coupled online to an
      electrospray-ionization time-of-flight mass spectrometer (ESI-TOF-MS) to analyze
      human urine for the identification of biomarkers specific for complications after
      allogeneic hematopoietic stem cell transplantation (HSCT). Sequencing of native
      proteins/peptides is necessary for the identification of possible new therapeutic
      targets.

PMID- 19110644
TI  - Spectral karyotyping and fluorescence in situ hybridization of murine cells.
AB  - Cytogenetic characterization of murine chromosomes using banding techniques like
      R- or G-banding is technically demanding due to the similar size and the
      acrocentric structure of all chromosomes. The molecular cytogenetic technique of
      spectral karyotyping (SKY) overcomes that difficulty by karyotyping metaphase
      chromosomes after different and simultaneous fluorescence labeling of the whole
      genome. SKY allows the detection and identification of numerical as well as
      structural chromosome aberrations with a resolution of approximately 2 Mb. The
      technique is applicable to all fast-proliferating cells, e.g., cells of the
      hematopoietic system like stem cells or T- and B-lymphocytes. It is also
      applicable to murine embryonic fibroblast or cells isolated from tissues with
      increased proliferation-especially tumor tissues. Furthermore, SKY is recommended
      for the cytogenetic characterization of newly established cell lines.

PMID- 19110645
TI  - Database setup for preclinical studies of gene-modified hematopoiesis.
AB  - Murine safety studies are routinely used for gathering preclinical safety and
      efficacy data and, for Phase I studies, Good Laboratory Practice (GLP) compliance
      is not mandated. However, extensive amounts of data must be gathered and
      analyzed. An inter-relational database is an effective tool for storing, sorting,
      and reviewing data.

PMID- 19110646
TI  - The US and EU regulatory perspectives on the clinical use of hematopoietic
      stem/progenitor cells genetically modified ex vivo by retroviral vectors.
AB  - A primary safety issue presented by human hematopoietic stem cells/progenitor
      cells (HS/PC) genetically modified by gammaretroviral or lentiviral vectors is
      the risk of oncogenesis. This risk is a potential consequence of either of the
      following events: (a) the possible unintended generation of replication-competent
      vector-derived viruses (replication-competent retrovirus, RCR; replication
      competent lentivirus, RCL) leading to neoplasia due to RCR/RCL infection of
      target and nontarget cells in vivo, or (b) intended vector integration in the
      chromosomal DNA of the target somatic cells leading to neoplasia due to
      insertional mutagenesis. These risks should be addressed in nonclinical and
      clinical studies. In the US and the EU, a combination of regulations and guidance
      documents are available to investigators and sponsors of gene therapy clinical
      trials. Guidance documents provide a facile way to adapt regulatory
      recommendations, in line with the changing state of the art in medical science.
      In the field of retroviral vectors, a number of innovations are being tested in
      nonclinical or clinical investigations, and each of these will raise their own
      regulatory issues. Some recent examples of these types of innovations include
      development of novel vector structures to minimize risks associated with vector
      integration, such as lentiviral vectors currently used in clinical trials for
      HS/PC modification that have been designed with deletions of the strong
      retroviral enhancer associated with oncogenesis.

PMID- 19110647
TI  - Review of hepatocyte transplantation.
AB  - BACKGROUND: Hepatocyte transplantation is a promising treatment for several liver
      diseases and can also be used as a "bridge" to liver transplantation in cases of
      liver failure. Although the first animal experiments with this technique began in
      1967, it was first applied in humans only in 1992. Unfortunately, unequivocal
      evidence of transplanted human hepatocyte function has been obtained in only one
      patient with Crigler-Najjar syndrome type I and, even then, the amount of
      bilirubin-UDP-glucuronosyltransferase enzyme activity derived from the
      transplanted cells was not sufficient to eliminate the patient's eventual need
      for organ transplantation. METHODS: A literature review was carried out using
      MEDLINE and library searches. RESULTS: This review considers the following: (1)
      alternatives or bridges to orthotopic liver transplantation (OLT); (2) solutions
      to the shortage of organs-the shortage of organ donors has impeded the
      development of human hepatocyte transplantation, and immortalized hepatocytes in
      particular could provide an unlimited supply of transplantable cells in a nearly
      future; (3) future directions. We review these efforts along with hepatocyte
      transplantation over the last 13 years.

PMID- 19110648
TI  - Life support of artificial liver: development of a bioartificial liver to treat
      liver failure.
AB  - In recent years there has been a particular focus on research regarding tissue
      engineering targeting the liver, especially in terms of what types of cells and
      extracellular matrices should be organized and in what type of environments to
      create an artificial liver, i.e., a life-saving organ. The ideal is to use
      healthy human liver cells as a source of cells for such research, but there is an
      extreme shortage of human-donor livers that can be used for cell isolation.
      Therefore, we are presently working on the differentiation of embryonic stem
      cells into liver cells as well as reversibly immortalized human liver cell lines
      that can be cultured in large quantities and at low cost. We are also working on
      the development of a bioartificial liver (BAL) using such cells as a source.
      Herein, we introduce our findings on the current status of BAL development.

PMID- 19110650
TI  - Islet cell transplantation for the treatment of type 1 diabetes in the USA.
AB  - Islet cell transplantation (ICTx) is one of the most effective treatments for
      type 1 diabetes and is less invasive compared to whole organ transplantation. The
      US has been the leader in the research and clinical applications of ICTx for the
      last 40 years. ICTx requires complex procedures, including pancreas procurement
      and preservation; pancreas digestion; islet purification; and transplantation.
      Even with the dramatic progresses in each of the procedures listed above, there
      are still challenges to make ICTx the standard therapy. These challenges are: (1)
      obtaining enough islets from a single donor and (2) preventing graft loss due to
      allogenic rejection and recurrence of autoimmune islet destruction. A new
      preservation strategy for pancreata and pancreatic ducts using ET-Kyoto solution
      as well as a new islet purification method using iodixanol has substantially
      improved islet yields. Continuous research to improve the efficacy of islet
      isolation will solve the issue of obtaining enough islets from a single donor.
      Immunological tolerance is an ideal solution for the issue of rejection and
      autoimmune recurrence and a regulatory T cell strategy seems promising. Moreover,
      the SUITO index is a simple and powerful tool to assess engrafted islet mass and
      is, therefore, useful for evaluating the efficacy of new immunosuppressant
      strategies. Once ICTx becomes a standard treatment, the donor shortage will
      become the next challenge. Marginal or living donor islet transplantations could
      help alleviate this issue; however, bio-artificial islet transplantation with
      animal islets could be the ultimate solution.

PMID- 19110651
TI  - Liver failure after major hepatic resection.
AB  - INTRODUCTION: The consequence of excessive liver resection is the inexorable
      development of progressive liver failure characterised by the typical stigmata
      associated with this condition, including worsening coagulopathy,
      hyperbilirubinaemia and encephalopathy. The focus of this review will be to
      investigate factors contributing to hepatocyte loss and impaired regeneration.
      METHODS: A literature search was undertaken of Pubmed and related search engines,
      examining for articles relating to hepatic failure following major hepatectomy.
      RESULTS: In spite of improvements in adjuvant chemotherapy and increasing
      surgical confidence and expertise, the parameters determining how much liver can
      be resected have remained largely unchanged. A number of preoperative,
      intraoperative and post-operative factors all contribute to the likelihood of
      liver failure after surgery. CONCLUSIONS: Given the magnitude of the surgery,
      mortality and morbidity rates are extremely good. Careful patient selection and
      preservation of an obligate volume of remnant liver is essential. Modifiable
      causes of hepatic failure include avoidance of sepsis, drainage of cholestasis
      with restoration of enteric bile salts and judicious use of portal triad inflow
      occlusion intra-operatively. Avoidance of post-operative sepsis is most likely to
      be achieved by patient selection, meticulous intra-operative technique and post
      operative care. Modulation of portal vein pressures post-operatively may further
      help reduce the risk of liver failure.

PMID- 19110649
TI  - Current status of islet cell transplantation.
AB  - Despite substantial advances in islet isolation methods and immunosuppressive
      protocol, pancreatic islet cell transplantation remains an experimental procedure
      currently limited to the most severe cases of type 1 diabetes mellitus. The
      objectives of this treatment are to prevent severe hypoglycemic episodes in
      patients with hypoglycemia unawareness and to achieve a more physiological
      metabolic control. Insulin independence and long term-graft function with
      improvement of quality of life have been obtained in several international islet
      transplant centers. However, experimental trials of islet transplantation clearly
      highlighted several obstacles that remain to be overcome before the procedure
      could be proposed to a much larger patient population. This review provides a
      brief historical perspective of islet transplantation, islet isolation
      techniques, the transplant procedure, immunosuppressive therapy, and outlines
      current challenges and future directions in clinical islet transplantation.

PMID- 19110652
TI  - Biliary tract cancer treatment: 5,584 results from the Biliary Tract Cancer
      Statistics Registry from 1998 to 2004 in Japan.
AB  - BACKGROUND/PURPOSE: The results from the Japanese Biliary Tract Cancer Statistics
      Registry from 1988 to 1998 were reported in 2002. In the present study, we report
      here selectively summarized data as an overview of the 2006 follow-up survey of
      the registered cases from 1998 to 2004 for information bearing on problems with
      the treatment of cancer of the biliary tract. METHODS: A total of 5,584 patients
      were registered from 1998 to 2004. The site of cancer was the bile duct in 2,732
      patients, the gallbladder in 2,067, and the papilla of Vater in 785. Those cases
      were analyzed with regard to patient survival according to the extent of tumor
      invasion (pT), the extent of lymph node metastasis (pN) and the stage. RESULTS:
      The five-year survival rate after surgical resection was 33.1% for bile duct
      cancer, 41.6% for gallbladder cancer, and 52.8% for cancer of the papilla of
      Vater. For hilar or superior bile duct cancer, the 5-year survival rate was lower
      with an increase in the pT, pN and f stage, except pT3 vs. pT4, pN1 vs. pN2 and
      stage III vs. stage IVa. For middle or distal bile duct cancer, the 5-year
      survival rate was lower with increase in pT, pN and f stage, except pT2 vs. pT3,
      pN2 vs. pN3, stage II vs. stage III and stage III vs. stage IVa. For gallbladder
      cancer, the 5-year survival rate was lower with increase in pT, pN and f stage.
      For cancer of the papilla of Vater, the 5-year survival rate was lower with
      increase in pT, pN and f stage, except pT1 vs. pT2, pN1 vs. pN2, and stage III
      vs. stage IVa. CONCLUSIONS: In the present study, the outcomes of surgical
      treatment were better than that of the previous report from Japan and foreign
      countries. The pT, pN and stage of gallbladder cancer are well defined. However,
      there were no significant differences in some groups of those of bile duct cancer
      and cancer of the papilla of Vater.

PMID- 19110653
TI  - Management of postoperative arterial hemorrhage after pancreato-biliary surgery
      according to the site of bleeding: re-laparotomy or interventional radiology.
AB  - BACKGROUND/PURPOSE: Intra-abdominal arterial hemorrhage is still one of the most
      serious complications after pancreato-biliary surgery. We retrospectively
      analyzed our experiences with 15 patients in order to establish a therapeutic
      strategy for postoperative arterial hemorrhage following pancreato-biliary
      surgery. METHODS: Between August 1981 and November 2007, 15 patients developed
      massive intra-abdominal arterial bleeding after pancreato-biliary surgery. The
      initial surgery of these 15 patients were pylorus-preserving
      pancreatoduodenectomy (PPPD) (7 patients), hemihepatectomy and caudate lobectomy
      with extrahepatic bile duct resection or PPPD (4 patients), Whipple's
      pancreatoduodenectomy (PD) (3 patients), and total pancreatectomy (1 patient).
      Twelve patients were managed by transcatheter arterial embolization and three
      patients underwent re-laparotomy. RESULTS: Patients were divided into two groups
      according to the site of bleeding: SMA group, superior mesenteric artery (4
      patients); HA group, stump of gastroduodenal artery, right hepatic artery, common
      hepatic artery, or proper hepatic artery (11 patients). In the SMA group, re
      laparotomy and coil embolization for pseudoaneurysm were performed in three and
      one patients, respectively, but none of the patients survived. In the HA group,
      all 11 patients were managed by transcatheter arterial embolization. None of four
      patients who had major hepatectomy with extrahepatic bile duct resection
      survived. Six of seven patients (85.7%) who had pancreatectomy survived, although
      hepatic infarction occurred in four. CONCLUSIONS: Management of postoperative
      arterial hemorrhage after pancreato-biliary surgery should be done according to
      the site of bleeding and the initial operative procedure. Careful consideration
      is required for indication of interventional radiology for bleeding from SMA
      after pancreatectomy and hepatic artery after major hepatectomy with bilioenteric
      anastomosis.

PMID- 19110654
TI  - Biliopancreatic reflux-pathophysiology and clinical implications.
AB  - The common bile duct and the main pancreatic duct open into the duodenum, where
      they frequently form a common channel. The sphincter of Oddi is located at the
      distal end of the pancreatic and bile ducts; it regulates the outflow of bile and
      pancreatic juice. In patients with a pancreaticobiliary maljunction, the action
      of the sphincter does not functionally affect the junction. Therefore, in these
      patients, two-way regurgitation (pancreatobiliary and biliopancreatic reflux)
      occurs. This results in various pathological conditions of the biliary tract and
      the pancreas. Biliopancreatic reflux could be confirmed by: operative or
      postoperative T-tube cholangiography; CT combined with drip infusion
      cholangiography; histological detection of gallbladder cancer cells in the main
      pancreatic duct; and reflux of bile on the cut surface of the pancreas.
      Biliopancreatic reflux occurs frequently in patients with a long common channel.
      Although the true prevalence, degree, and pathophysiology of biliopancreatic
      reflux remain unclear, biliopancreatic reflux is related to the occurrence of
      acute pancreatitis. Obstruction of a long common channel easily causes bile flow
      into the pancreas. Even if no obstruction is present, biliopancreatic reflux can
      still result in acute pancreatitis in some cases.

PMID- 19110655
TI  - Secondary membranous glomerulonephritis associated with recipient residual
      lymphoma cells after allogeneic bone marrow transplantation.
AB  - A 29-year-old man with malignant lymphoma developed membranous nephropathy (MN)
      after allogeneic bone-marrow transplantation (BMT). There had been no obvious
      findings of graft versus host diseases (GVHD) after BMT, and the dosage of
      immunosuppressant drugs had not been reduced during this period. At the onset of
      MN, a few lymphoma cells still remained in the bone marrow; the patient achieved
      complete remission of MN after the disappearance of the lymphoma cells. In this
      case it is suggested that immune complexes including antigens expressed by
      lymphoma cells might induce MN. Therefore, this is a significant case that may
      reveal an alternative mechanism of the onset of MN related to BMT.

PMID- 19110656
TI  - Beetle visitations, and associations with quantitative variation of attractants
      in floral odors of Homalomena propinqua (Araceae).
AB  - This study investigated floral visitations of two beetles, Parastasia bimaculata
      (Scarabaeidae) and Chaloenus schawalleri (Chrysomelidae), and examined
      associations between beetle visitations and variation in attractant traits, such
      as quantitative variations of attractants in floral odors and heat generation of
      spadices in Homalomena propinqua (Araceae). Observations showed P. bimaculata
      visited pistillate-phase inflorescences most frequently during heat generation,
      whereas C. schawalleri visited regardless of floral stages and heat generation.
      Chemical analyses of five dominant components of floral odors showed quantities
      of 2-butanol, veratrole, and alpha-pinene during the pistillate phase were the
      most abundant during all floral stages, and increased during heat generation.
      When testing combinations of these five authentic chemicals, some mixtures
      including 2-butanol or veratrole or both attracted both beetles, and veratrole
      attracted C. schawalleri. These results strongly suggested that the increased
      emission of floral odor attractants which accompanied heat generation influences
      floral visitations by P. bimaculata, but not by C. schawalleri. We therefore
      hypothesize that P. bimaculataaculata is a reliable pollinator, and that
      variation in attractant traits is a honest signal for P. bimaculata to seek
      rewards. In contrast, C. schawalleri can detect the signal even at low levels,
      and so visits inflorescences steadily during all floral stages.

PMID- 19110657
TI  - Geometric characters of the radius and tibia in Macaca mulatta and Macaca
      fascicularis.
AB  - We performed comparative analyses of four cross-sections of the distal radius and
      tibia in two species of macaque to clarify the relationships between bone
      morphology and locomotor type. The lengths of bones and five bone geometric
      properties in each section were examined and compared separately in both female
      and male Macaca mulatta and Macaca fascicularis. In M. mulatta, there were no
      significant gender-specific differences in either the radius or the tibia. In
      contrast, the radius and tibia of male M. fascicularis had greater geometric
      parameters in the 20% and 40% positions relative to the 5% and 10% positions from
      the distal end than those of their female counterparts. The radius and tibia of
      M. mulatta were relatively longer than those of M. fascicularis, and the
      sectional parameters of the tibia of M. mulatta were relatively larger than those
      of M. fascicularis. Standardization of the log-transformed bone length between
      the species revealed larger radial cortical bone areas in M. fascicularis. In
      contrast, there were minimal differences in the tibial cortical bone areas
      between the two species. This study suggests that the observed distinctions in
      bone geometry in female and male M. fascicularis may be due to gender-specific
      differences in the muscle weights of the forearm and calf, which may underlie the
      divergence in the leaping abilities of females and males of this species. Taken
      together, these results of interspecies comparisons may be related to the fact
      that arboreal primates such as M. fascicularis undergo compressive mechanical
      stress due to the forelimb lead that occurs as the animal descends a sloping
      trunk or bridges a tree gap downward, while terrestrial primates such as M.
      mulatta move on nearly flat substrates. Differences in fore- and hind-limb bone
      properties between the two species are discussed with regard to functional
      morphology and locomotor type.

PMID- 19110658
TI  - Diagnostic efficacy of 0, 30, 45, 60, 90 and 120 min growth hormone samples in
      insulin tolerance test: utility of growth hormone measurement at different time
      points and a cost-effective analysis.
AB  - OBJECTIVE: To determine the utility of growth hormone (GH) measurement with the
      insulin tolerance test (ITT), and to carry out a cost-effective analysis of the
      diagnosis of GH deficiency. MATERIAL AND METHODS: Ninety-nine patients clinically
      suspected of GH deficiency were evaluated over a period of 14 months (January
      2005 to April 2006). Post-insulin samples of GH and blood glucose (BG) samples
      were drawn at six different time-points. Serum GH levels of <10 microg/L
      (prepubertal) and <6.1 microg/L (adolescents) were taken as cut-off for the
      normal response. RESULTS: Ninety-nine ITTs were carried out during the study
      period, and GH levels were found to be deficient in 47 subjects. Specificities at
      different time-points were 0%, 54%, 77%, 62%, 39% and 23% for 0, 30, 45, 60, 90
      and 120 min, respectively, in the prepubertal group, and 5%, 41%, 80%, 87%, 77%
      and 46% at the same time-points for the adolescent group. Accuracy was highest at
      45 and 60 min in both the prepubertal and adolescent groups. The receiver
      operating characteristic curve showed that the highest area under the curve was
      found in samples drawn at 45, 60 and 90 min in both the prepubertal and
      adolescent groups. CONCLUSION: Our data suggest that 0, 45, 60 and 90 min samples
      are sufficient for diagnosing GH deficiency, which could lead to potential cost
      reductions of up to 29.8%.

PMID- 19110659
TI  - Type-2 diabetes down-regulates glucose transporter proteins and genes of the
      human blood leukocytes.
AB  - OBJECTIVE: White blood cells are essential in mediating immune and inflammatory
      responses. A prominent feature of these cells during activation of the immune
      function is increased glucose utilization, and this is dependent on the
      functioning of specific glucose transporter (GLUT) isoforms. The few data
      available on leukocyte glucose transporter expression are limited to type-2
      diabetes mellitus, and nothing is known about its regulation. MATERIAL AND
      METHODS: Peripheral blood was drawn from 35 healthy controls and 35 diabetic
      subjects. Expression of GLUT1, GLUT3 and GLUT4 was determined in the leukocytes
      of healthy individuals and diabetic patients by flow cytometry, Western blot and
      semi-quantitative RT-PCR. RESULTS: GLUT 3 was decreased in granulocytes,
      lymphocytes and monocytes from diabetic patients. In monocytes, GLUT3 and GLUT4
      were reduced in type-2 diabetic patients. In leukocytes of diabetic patients,
      GLUT1 and GLUT4, protein and mRNA were unchanged, but GLUT3 protein and mRNA
      levels were down-regulated compared to those of healthy controls. CONCLUSION:
      Elevated glucose concentration affects leukocyte GLUT expression. Decreased
      expression of GLUT isoforms in leukocytes may be responsible for diminished
      activation of diabetic leukocytes. These situations possibly contribute to a
      predisposition to infection and to a decreased immune response in diabetes.

PMID- 19110660
TI  - Enhanced propensity of T lymphocytes in patients with systemic lupus
      erythematosus to apoptosis in the presence of tumour necrosis factor alpha.
AB  - OBJECTIVE: To determine the effect of inflammation through exposure to tumour
      necrosis factor (TNF)alpha on T lymphocytes in patients with systemic lupus
      erythematosus (SLE). METHODS: We studied the effect of TNFalpha on T-lymphocyte
      apoptosis in patients with SLE, rheumatoid arthritis (RA), and in healthy
      controls. Apoptosis of CD4 and CD8 T lymphocytes and naive and memory
      subpopulations was determined by flow cytometry using 7-amino-actinomycin D
      (7AAD) and propidium iodide (PI). In SLE, apoptosis was studied in patients with
      active and inactive disease and in patients on different medications. RESULTS:
      TNFalpha enhanced apoptosis of anti-CD3-activated T lymphocytes. The percentage
      of apoptotic cells was significantly higher in T lymphocytes from patients with
      SLE than RA patients and healthy controls. After 3 days of culture, 38% of CD4+
      and 37% of CD8+ cells from SLE patients underwent apoptosis in the presence of
      TNFalpha compared with 25% CD4+ and 26% CD8+ T cells from the controls (p<0.001).
      In healthy controls, more memory than naive T lymphocytes underwent apoptosis. By
      contrast, in patients with SLE, more naive T cells underwent apoptosis with
      TNFalpha (p<0.01). Enhanced apoptosis of T cells in SLE was independent of
      disease activity or medication. Finally, inhibition experiments showed that
      apoptosis in the presence of TNFalpha was only partly blocked with anti-Fas
      ligand (FasL) antibody. CONCLUSIONS: This study demonstrates that T lymphocytes
      in patients with SLE are more prone to apoptosis in the presence of TNFalpha than
      T lymphocytes from healthy controls. Defects in TNFalpha signalling pathways
      rather than distribution of TNF receptors (TNFRs) probably explain the enhanced
      apoptosis in SLE.

PMID- 19110661
TI  - Prevalence of celiac disease among dyspeptic patients: a community-based case
      control study.
AB  - BACKGROUND/AIMS: To determine the relation between undiagnosed celiac disease and
      dyspepsia in the community. METHODS: Patients presenting to the gastroenterology
      outpatient clinic of Mersin University Hospital, aged between 18 and 70 years and
      with no malignancy, malabsorption, chronic diarrhea, inflammatory bowel disease,
      diabetes mellitus, heart failure or renal failure, were asked to complete a
      questionnaire for functional bowel disease (based on Rome II criteria for
      irritable bowel syndrome and dyspepsia). The patients diagnosed with dyspepsia
      based on Rome II criteria formed the dyspepsia group and those with
      gastrointestinal complaints other than dyspepsia and irritable bowel syndrome
      formed the control group. Serum tissue transglutaminase antibody (anti-tTG) was
      determined in all patients. The patients with anti-tTG levels of >20U/ml
      underwent endoscopic duodenal biopsy. RESULTS: The study included a total of 137
      patients, of whom 69 (50.4%) were assigned into the dyspepsia group and 68
      (49.6%) into the control group. Of 137 patients, 24 (17.5%) had an anti-tTG level
      of > or =20U/ml: 14 in the dyspepsia group (20.3%) and 10 in the control group
      (14.7%), with no significant difference between the groups (p=0.39). Of the 24
      patients positive for anti-tTG, 15 (64.5%) underwent endoscopy, and of these 15
      patients, 8 (53.3%) had endoscopic duodenal biopsy. Biopsy revealed that of the 4
      patients in the dyspepsia group, 3 (75%) had Marsh type 0 histology (IEL<40,
      normal crypt) and 1 (25%) had Marsh type 3a histology. Of the 4 patients in the
      control group, 3 (75%) had Marsh type 0 histology and 1 (25%) had Marsh type 3a
      histology. Histopathological examinations showed celiac disease in 2 out of the 8
      patients (25%) positive for anti-tTG who underwent biopsy. Intention to treat
      analyses revealed that 1 of 69 patients in the dyspepsia group (1.44%) and 1 of
      68 patients in the control group (1.47%) had celiac disease. CONCLUSIONS: Celiac
      disease in this patient population had a high prevalence. Further studies with
      larger sample sizes are needed to confirm the relation between dyspepsia and
      celiac disease.

PMID- 19110662
TI  - Factors related to non-alcoholic fatty liver disease in obese children.
AB  - BACKGROUND/AIMS: The incidence of non-alcoholic fatty liver disease has been
      increasing parallel to obesity in the pediatric age group. This study aimed to
      analyze the factors that are related to non-alcoholic fatty liver disease in
      obese children. METHODS: 101 obese children and 68 non-obese controls were
      included in the study. Liver steatosis was investigated by ultrasonography. The
      subjects were divided into three groups: 53 obese patients with fatty liver
      (Group I), 48 obese patients without steatosis (Group II), and 68 controls
      without steatosis (Group III). Group I was further divided into those with Grade
      1 steatosis (44 patients, Group Ia) and higher grades of steatosis (9 patients,
      Group Ib). The relationships of body mass index, serum ALT, lipids, leptin, and
      insulin resistance index with steatosis were analyzed. RESULTS: 52.4% of obese
      children had fatty liver and 13.8% had high ALT levels. Additionally, all
      patients with elevated ALT levels were seen to have liver steatosis by
      ultrasonography. Leptin and insulin resistance index levels were higher in obese
      groups than controls; however, the difference disappeared when these levels were
      adjusted for body mass index. ALT levels were higher in Group I (31.5+/-30.2)
      than Group II (18.0+/-7.1) and Group III (14.5+/-5.2) (p<0.05). Group Ib showed
      higher VLDL and ALT levels than Group Ia (p<0.05). Multiple regression analysis
      revealed that body mass index was the most important determinant of liver
      steatosis, while body mass index and VLDL were the determinants of higher ALT
      levels. CONCLUSIONS: We suggest that body mass index and VLDL are the most
      important determinants of non-alcoholic fatty liver disease and elevated ALT
      levels in obese children. The contribution of leptin to this process could not be
      determined in our findings.

PMID- 19110663
TI  - The effect of grape seed extract on radiation-induced oxidative stress in the rat
      liver.
AB  - BACKGROUND/AIMS: The tolerance of the liver is considerably low when an effective
      radiation (RTx) dose needs to be delivered in patients in whom either their liver
      or whole body area has to be irradiated. The aim of this study was to evaluate
      the possible protective effect of grape seed extract on liver toxicity induced by
      RTx in the rat liver. METHODS: We used four groups, each consisting of 12 healthy
      male Wistar rats. RTx-grape seed extract group: rats were given grape seed
      extract (100 mg/kg) orally for seven days, following 8 Gy whole body irradiation,
      and grape seed extract was maintained for four days. RTx group: the same protocol
      was applied in this group; however, they received distilled water instead of
      grape seed extract. Grape seed extract group: only grape seed extract solution
      was administered for 11 consecutive days in the same fashion. CONTROL GROUP: only
      distilled water (orally) was administered in a similar manner. The level of
      malondialdehyde, an end product of lipid peroxidation, and the activities of
      superoxide dismutase and catalase, two important endogenous antioxidants, were
      evaluated in tissue homogenates. RESULTS: Grape seed extract was seen to protect
      the cellular membrane from oxidative damage and consequently from protein and
      lipid oxidation. In the RTx group, malondialdehyde levels were extremely higher
      than those of the grape seed extract-RTx group (p<0.001). Grape seed extract
      administration moderately reserved the malondialdehyde levels. RTx therapy
      decreased superoxide dismutase and catalase activities in the liver homogenates
      (p<0.001), and these alterations were significantly reversed by grape seed
      extract treatment (p<0.001). There were no differences between the grape seed
      extract- RTx, grape seed extract and control groups with regard to antioxidant
      activity (p>0.05). CONCLUSIONS: The levels of antioxidant parameters on RTx
      induced liver toxicity were restored to control values with grape seed extract
      therapy. Grape seed extract may be promising as a therapeutic option in RTx
      induced oxidative stress in the rat liver.

PMID- 19110664
TI  - Lamivudine resistance in untreated chronic hepatitis B patients in Turkey.
AB  - BACKGROUND/AIMS: Hepatitis B virus infection is an epidemiological problem
      throughout the world, including in Turkey. Lamivudine is one of the hepatitis B
      virus reverse-transcriptase inhibitors used for the treatment of chronic
      hepatitis B virus infection. Lamivudine resistance can develop not only following
      treatment; it can also be seen in untreated patients. This resistance is related
      with structural changes in the tyrosine-methionine- aspartate-aspartate motif of
      the polymerase enzyme gene. Our objective was to evaluate the prevalence of
      lamivudine resistance in Turkish chronic hepatitis B virus-infected patients with
      D genotype before antiviral treatment. METHODS: Seventyseven patients with
      chronic hepatitis B virus infection were evaluated for viral loads, HBeAg, anti
      HBe antibody, ALT levels, histological activity index, and tyrosine-methionine
      aspartateaspartate mutations. RESULTS: Tyrosine-methionine-aspartateaspartate
      motif mutations were determined in 3 of 24 HBeAg positive and 3 of 53 anti-HBe
      positive patients with a rate of 7.8%. Two of the mutations were YIDD and 4 were
      YVDD. Median ALT value in patients with mutations was 88 IU/L (range 55-276) and
      histological activity index was 9 (range 6-10); these values in patients without
      mutations were 58 (range 19- 176) and 10 (range 2-18), respectively. Knodell
      fibrosis scores of patients were as follows: 0: 13.2%, 1: 28.9%, 2: 21.1%, 3:
      34.2%, and 4: 2.6%. There were no significant differences between the patients
      regarding Knodell fibrosis scores. One patient was diagnosed as cirrhosis.
      CONCLUSIONS: Evaluation of chronic hepatitis B virus patients for lamivudine
      resistance and planning the treatment accordingly may prevent complications and
      can increase the effectiveness of the treatment.

PMID- 19110665
TI  - Prevalence and clinical significance of SEN-H virus in chronic hepatitis B, C and
      delta infections in Turkey.
AB  - BACKGROUND/AIMS: SEN viruses are transmitted parenterally and can cause post
      transfusion hepatitis. The prevalence and clinical significance of SEN viruses
      have been investigated in patients with chronic hepatitis C and B but not in D.
      We aimed to determine the prevalence and clinical significance of SEN viruses- H
      in patients with chronic hepatitis C, B and delta in Turkey. METHODS: SEN viruses
      H was analyzed in 85 patients with chronic viral hepatitis (30 HCV, 30 HBV and 25
      HDV) and 43 non-professional blood donors. HBV DNA, HCV RNA and HDV RNA were
      positive in patients with hepatitis B, C and D, respectively. SEN viruses-H DNA
      was detected by semi-nested polymerase chain reaction method (L2AS, C5S primer in
      first step, L2AS, D11 in second step) after extraction of DNA from sera
      (NucleoSpin blood; Macherey-Nagel GmbH & Co KG, Germany). RESULTS: SEN viruses-H
      DNA was found to be positive in 7/30 (23.3%), 10/30 (33.3%), 6/25 (24%), and 7/43
      (16.2%) of patients with chronic C, B, and D hepatitis and healthy blood donors,
      respectively. There was no significant difference in clinical features and
      treatment response between SEN viruses- H-positive and -negative patients with
      chronic viral hepatitis. CONCLUSIONS: SEN viruses is more frequent in chronic
      hepatitis patients than in healthy blood donors. These results indicate that SEN
      viruses has no effect on the clinical course and treatment response of chronic
      viral hepatitis.

PMID- 19110666
TI  - Easy sphincterotomy in patients with Billroth II gastrectomy: a new technique.
AB  - BACKGROUND/AIMS: ERCP and endoscopic sphincterotomy in patients with Billroth II
      gastrectomy are technically more difficult due to the reversed anatomy. We
      developed a new guidewire sphincterotome that includes two 15-mm non-isolated
      metal parts, one of which is located 12 cm from the distal tip and the other in
      the proximal end. The aim of this study was to evaluate the feasibility of and
      outcomes with the new sphincterotome for sphincterotomy in patients with Billroth
      II gastrectomy. METHODS: Between January 2004 and March 2007, 11 patients with
      Billroth II gastrectomy underwent endoscopic sphincterotomy with the new
      guidewire sphincterotome. Procedures were initiated by deep cannulation of the
      bile duct with a standard catheter and guidewire sphincterotome. After
      cholangiography, the catheter was withdrawn with 0.5 to 1 cm of its tip outside
      the duodenoscope. The distal non-isolated part of the sphincterotome was placed
      in the papillary orifice. In order to reach the proper position, the
      duodenoscope's elevator was moved to the downward position, the up-down dial was
      turned slightly in the downward direction, and then the duodenoscope was pushed
      slightly forward. Finally, sphincterotomy was performed in the 6 o'clock
      direction. RESULTS: Sphincterotomy with the new sphincterotome was successfully
      achieved in all patients without using protective pancreatic stents. Seven
      patients had common bile duct stones, two pancreatitis, one odditis, and another
      one persistent bile duct leakage. There were no sphincterotomyrelated
      complications or death during this study. CONCLUSIONS: In this pilot study,
      endoscopic sphincterotomy with a new guidewire sphincterotome in patients with
      Billroth II gastrectomy was found to be clinically successful, concise, easy to
      perform, efficient, and reliable. However, further large comparative studies are
      needed for a definite conclusion.

PMID- 19110667
TI  - Gastric polypoid intramucosal carcinoma and an adjacently located leiomyoma at
      the cardia.
AB  - We report a 65-year-old patient with a gastric polyp of 2.5 cm in diameter
      located at the cardia on upper gastrointestinal (GI) endoscopy. Pathological
      examination of the excised polyp showed intramucosal carcinoma. Endoscopic
      ultrasonography (EUS) reported the lesion as early gastric carcinoma with
      probable submucosal involvement. On serial sections of the gastrectomy material,
      the lesion was an intramucosal carcinoma and surprisingly there was a leiomyoma
      located adjacently.

PMID- 19110668
TI  - Diffuse gastrointestinal involvement of mantle cell lymphoma.
AB  - The gastrointestinal tract is the predominant site of appearance of extranodal
      non-Hodgkin lymphomas. The most frequent endoscopic finding of mantle cell
      lymphoma is multiple lymphomatous polyposis, which is a very rare entity.
      Multiple lymphomatous polyposis is characterized by multiple polypoid lesions
      involving long segments of the gastrointestinal tract and it accounts for 2% of
      primary gastrointestinal tract lymphomas. A 68-year-old patient was admitted to
      our clinic with intermittent diarrhea, weight loss, hematochezia and fatigue.
      Multiple lymphomatous polyposis was detected on the endoscopic evaluations.
      Gastrointestinal mantle cell lymphoma was confirmed with histopathological and
      immunohistochemical studies on biopsy specimens from colon, small intestine and
      stomach. The patient was successfully treated by combination chemotherapy.

PMID- 19110669
TI  - A rare case of adult intestinal intussusception: epithelioid type mesenchymal
      tumor of the small intestine.
AB  - Small bowel intussusception is a rare cause of adult acute abdomen, in which an
      intraluminal neoplasm is the most frequent cause. Small bowel tumors are uncommon
      and can have a long delay prior to diagnosis. We present a case of intestinal
      intussusception originating from a rare variant of small bowel mesenchymal tumor,
      presenting with a hematologic disorder.

PMID- 19110670
TI  - A case of angiographically verified non-occlusive mesentery ischemia induced by
      digitalis.
AB  - Here we present a case of non-occlusive mesentery ischemia induced by digitalis,
      which was verified angiographically. Nonocclusive mesentery ischemia, a subgroup
      of "acute mesentery ischemia", is known as a period of intestinal ischemic
      hypoperfusion without a demonstrable vascular occlusion in the mesentery bed. It
      can be caused by factors leading to splanchnic hypoperfusion, which can be of
      cardiac, renal or hepatic origin. In addition, it can be induced by certain drugs
      such as digitalis, ergotamines and vasoactive agents. In clinical practice,
      digitalis toxicity is commonly seen. In contrast, non-occlusive mesentery
      ischemia secondary to digitalis is quite rare. However, nonocclusive mesentery
      ischemia should be included in the differential diagnosis for patients who
      develop sudden and diffuse abdominal pain while on digitalis therapy.

PMID- 19110671
TI  - Imaging characteristics of liver metastasis from gastrointestinal stromal tumor
      before and after imatinib mesylate treatment.
AB  - Our objective was to show the unusual imaging characteristics of cystic liver
      metastases from a malignant gastrointestinal stromal tumor before and after
      treatment with imatinib mesylate.

PMID- 19110672
TI  - Smoking as an important factor increasing risk of Helicobacter pylori.

PMID- 19110673
TI  - Coincidental occurrence of granular cell tumor and gastrointestinal stromal tumor
      in a patient.

PMID- 19110674
TI  - Gastrointestinal sarcoidosis mimicking colonic cancer.

PMID- 19110675
TI  - Prevalence of cholelithiasis in a Turkish population of end stage renal failure
      patients and related risk factors: experience of a center from Turkey.

PMID- 19110676
TI  - Polypoid lesions of the gallbladder smaller than 10 mm.

PMID- 19110678
TI  - Hair today, more hair tomorrow?  The balding pate can be treated with drugs, hair
      transplants--or both.  But the search for the ultimate solution to hair loss goes
      on.

PMID- 19110679
TI  - Surviving the Medicare maze.  Medicare, once the post-retirement panacea, is now
      just the starting point for seniors' health care coverage.

PMID- 19110677
TI  - Mental health, treatment preferences, advance care planning, location, and
      quality of death in advanced cancer patients with dependent children.
AB  - BACKGROUND: Clinicians observe that advanced cancer patients with dependent
      children agonize over the impact their death will have on their children. The
      objective of this study was to determine empirically whether advanced cancer
      patients with and without dependent children differ in treatment preferences,
      mental health, and end-of-life (EOL) outcomes. METHODS: Coping with Cancer is a
      National Cancer Institute/National Institute of Mental Health-funded, multi
      institutional, prospective cohort study of 668 patients with advanced cancer.
      Patients with and without dependent children were compared on rates of
      psychiatric disorders, advance care planning (ACP), EOL care, quality of their
      last week of life, and location of death. RESULTS: In adjusted analyses, patients
      with advanced cancer who had dependent children were more likely to meet panic
      disorder criteria (adjusted odds ratio [AOR], 5.41; 95% confidence interval [95%
      CI], 2.13-13.69), more likely to be worried (mean difference in standard
      deviations [delta], 0.09; P=.006), and more likely to prefer aggressive treatment
      over palliative care (AOR, 1.77; 95% CI, 1.07-2.93). Patients with dependent
      children were less likely to engage in ACP (eg, do not resuscitate orders: AOR,
      0.44; 95% CI, 0.26-0.75) and had a worse quality of life in the last week of life
      (delta, 0.15; P=.007). Among spousal caregivers, those with dependent children
      were more likely to meet criteria for major depressive disorder (AOR, 4.53; 95%
      CI, 1.47-14) and generalized anxiety disorder (AOR, 3.95; 95% CI, 1.29-12.16).
      CONCLUSIONS: Patients with dependent children were more anxious, were less likely
      to engage in ACP, and were more likely to have a worse quality of life in their
      last week of life. Advanced cancer patients and spousal caregivers with dependent
      children represent a particularly distressed group that warrants further clinical
      attention, research, and support.

PMID- 19110680
TI  - The sunshine D-lemma.  Sunlight causes skin cancer, but it also produces vitamin
      D, a substance that seems to prevent some types of cancer and possibly other
      diseases.

PMID- 19110681
TI  - By the way, doctor. Both of my father's sisters died of breast cancer years ago,
      one before menopause, the other just after. I have an 18-year-old daughter. I've
      been wondering if I should talk to her about getting tested for the breast cancer
      gene. I'm the dad.

PMID- 19110683
TI  - Making grant $ stretch through networking. HIV clients become peers, peers become
      staff.

PMID- 19110682
TI  - Yes we can? Obama's win brings hope to HIV/AIDS groups. Election raises optimism
      for more funding.

PMID- 19110684
TI  - Adherence strategies. ASO's collaborate with medical providers. Services help
      patients improve adherence.

PMID- 19110685
TI  - Working with homeless shelters to expand reach. Model works in other settings, as
      well.

PMID- 19110686
TI  - Research focuses on rapid HIV testing.

PMID- 19110687
TI  - Time to step up HIV testing in women.

PMID- 19110688
TI  - FDA notifications. FDA approves generic lamivudine.

PMID- 19110689
TI  - Mechanical bowel preparation before colorectal surgery?

PMID- 19110690
TI  - Thymoma.

PMID- 19110691
TI  - Concepts and issues with interspecies scaling in zoological pharmacology.
AB  - Zoologic medicine practitioners take approved agents (veterinary or human) and
      extrapolate their use to nonapproved species. The decision on dose, duration, and
      interval is often made with limited species-specific pharmacokinetic information.
      Because of the monetary value of these animals or their status as endangered
      species, this method of "trial and error" for therapeutic dosage selection is
      inappropriate. In zoologic medicine, various methods have been used in an attempt
      to extrapolate or predict safe and effective dosage regimens. The simplest and
      typical method of extrapolating a dosage to a nondomestic species is to use a
      mg/kg dose established for another domestic species or humans. However, this
      calculation results in a linear increase in the amount of drug administered as
      body weight increases. Although common, this method tends to overdose large
      animals and underdose small animals. The second method is similar, except that it
      takes the approved dose in a specific species and makes an additional assumption
      that links the dosage to a physiologic function or anatomic feature. Examples are
      the use of basal metabolic rate or body-surface area as the basis for dosage
      extrapolation. Allometric scaling of pharmacokinetic parameters is the final
      method of dosage extrapolation between species. This is commonly used in the
      pharmaceutical industry to establish the first dosage in human drug
      investigations. Adaptation of this method for zoologic medicine may enhance our
      ability to estimate therapeutic dosages for nondomestic species. This review
      discusses and compares these three methods for dosage selection and provides
      examples of extrapolation from the literature.

PMID- 19110692
TI  - Analysis of biochemical markers of bone metabolism in Asian elephants (Elephas
      maximus).
AB  - Two human enzyme immunoassays (EIA) and one radioimmunoassay (RIA) were validated
      and used to measure osteocalcin (OC), bone alkaline phosphatase (BAP), and the
      cross-linked telopeptide domain of type I collagen (ICTP), in serum from Asian
      elephants (Elephas maximus). Sera from four adult females sampled on 7
      consecutive days were also analyzed to assess the existence and magnitude of
      intraindividual day-to-day variability of the serum concentration of these
      markers. Sample dilution curves were parallel with assay standard curves, which
      demonstrated that excellent cross reactivity existed between assay antibodies and
      elephants marker antigens. Statistically significant inverse correlations were
      found between age and concentrations of all three markers: BAP, r = -0.862 (P <
      0.01); OC, r = -0.788 (P < 0.002); and ICTP, r = -0.848 (P < 0.01). Strong
      positive correlations were found between BAP and OC (r = 0.797, P < 0.01), OC and
      ICTP (r = 0.860, P < 0.01), and between BAP and ICTP (r = 0.958, P < 0.01). No
      statistically significant intraindividual variability was found over 7 days in
      the four adult females for any of the markers assessed (OC: P = 0.089; ICTP: P =
      0.642; BAP: P = 0.146; n=4 in each case). The overall coefficient of variability
      observed in this group of animals was 10.3%, 7.4%, and 5.5% for OC, BAP, and
      ICTP, respectively. These results suggest a potential role for biochemical
      markers of bone turnover in monitoring skeletal health and bone disease in Asian
      elephants.

PMID- 19110693
TI  - Serologic response to West Nile virus vaccination in the greater one-horned
      rhinoceros (Rhinoceros unicornis).
AB  - Vaccination has been an important component of preventative health care programs
      of North American zoologic institutions in their protection of valuable species
      against West Nile virus (WNV) infection since its detection in 1999. Although
      approved only for horses, commercial WNV vaccine has been used for the purpose of
      protection of nondomestic species, including avian, equid, and rhinoceros
      species. Currently, there are two commercial equine vaccines available, a killed
      vaccine and a recombinant viral-vectored vaccine. Both products have been used
      for the vaccination of Greater One-horned rhinoceroses (Rhinoceros unicornis)
      held in North American zoologic institutions. In this study, the efficacy of
      these vaccines was evaluated in Greater One-horned rhinoceroses based on the
      humoral immune response stimulated by vaccine administration. Five rhinoceroses
      were vaccinated in 2005 by using the killed equine vaccine and four received
      boosters in 2006 by using the recombinant vaccine. Rhinoceroses were evaluated
      for differences in pre- and postvaccination neutralizing antibody titer and gamma
      and beta globulins on serum protein electrophoresis. No changes were observed
      after administration of the killed vaccine; however, antibody titers were
      observed in two of four rhinoceroses after administration of the recombinant
      vaccine. No significant changes were observed in the serum protein
      electrophoresis after either vaccine. Based on these findings, the WNV
      recombinant vaccine appeared to induce a more measurable humoral immune response
      than the killed product in the Greater One-horned rhinoceros. However, further
      investigation of both vaccines is warranted to evaluate whether changes in the
      frequency of administration, dosage, or adjuvant might stimulate an improved
      humoral response in these animals.

PMID- 19110694
TI  - Determination of a sedative protocol for use in California sea lions (Zalophus
      californianus) with neurologic abnormalities undergoing electroencephalographic
      examination.
AB  - Sedation in sea lions exhibiting abnormal neurologic signs may require
      modification of established sedatior protocols because of the likely interaction
      between effects of the sedative and physiologic changes in diseased animals The
      effects of two sedative combinations, 0.07 mg/kg medetomidine and 0.07 mg/kg
      medetomidine plus 0.2 mg/kg butorphanol, were compared between California sea
      lions (Zalophus californianus) with signs of neurologic dysfunctior (n=33) and
      without neurologic signs (n=8). Sedation depth was scored on a scale of 0 (no
      effect) to 4 (profound sedation) assessed by response to auditory, tactile, and
      visual stimuli at the time of perceived maximal sedative effect In the
      medetomidine-alone group, sea lions with neurologic signs attained a median
      sedation score of 4 compared to a median sedation score of 1 in the clinically
      normal sea lions. Sea lions with and without neurologic signs giver medetomidine
      butorphanol attained a median sedation score of 4. No statistically significant
      difference in time to induction and respiratory rate was found between the two
      sedation protocols in all sea lions. In the sea lions with neurologic signs, the
      recovery time from medetomidine-butorphanol sedation was prolonged (P < 0.01) and
      minimum recorded heart rates, although remaining within normal physiologic
      limits, were lower (P = 0.02) when compared to the sea lions administered
      medetomidine alone. Muscle jerks were observed in many animals given medetomidine
      butorphanol and were detrimental to the diagnostic quality of the
      electroencephalogram (EEG) recording. Medetomidine alone at a dose rate of 0.07
      mg/kg thus provides adequate and safe sedation in sea lions with neurologic signs
      undergoing EEG evaluation.

PMID- 19110695
TI  - Hematologic and serum biochemistry reference values in wild-caught white-footed
      tamarins (Saguinus leucopus) housed in captivity.
AB  - The white-footed tamarin (Saguinus leucopus) is an endangered primate that lives
      in a small forest corridor in northern Colombia, South America. Hematologic and
      serum biochemistry reference values are important tools in evaluating the health
      of the white-footed tamarin and serve to promote the survival of this species.
      The purpose of this study was to establish diagnostically important hematologic
      and serum biochemistry reference values for healthy white-footed tamarins and to
      determine whether there was significant variation with respect to age class
      (juveniles, adults), gender, and housing facility. Blood samples were collected
      for hematologic and serum biochemistry measurements from 29 wild-caught captive
      tamarins during February and April 2005, housed at three different facilities in
      central Colombia. Hematology and serum biochemistry values were similar in adults
      and juveniles. Female white-footed tamarins had absolute reticulocyte counts that
      were lower than those of male tamarins and males had lower serum chloride
      concentrations than female tamarins. Mean values for hemoglobin, mean cell
      hemoglobin, serum total protein, albumin, glucose, and alkaline phosphatase
      varied among the three housing facilities. Twenty-two of the 29 tamarins sampled
      were microfilaria-positive and had significantly higher mean serum alkaline
      phosphatase concentrations. Among the 29 tamarins sampled in this study, serum
      values for mean alkaline phosphatase and creatine kinase concentrations were
      higher than reported values for other mammals. The reference intervals determined
      in this study were comparable to normal ranges reported for other members of the
      family Callitrichidae.

PMID- 19110696
TI  - Reversible immobilization of asiatic black bear (Ursus thibetanus) with
      detomidine-tiletamine-zolazepam and atipamezole.
AB  - Chemical immobilization of free-ranging and captive wildlife is often required in
      many clinical situations. In this trial, tiletamine-zolazepam was combined with
      the alpha2-agonist, detomidine, in order to use the least amount of anesthetic
      drug possible to achieve a rapid immobilization; to ensure safety for animals and
      operators; and to be easily reversible with specific antagonists for a fast
      recovery. Twelve captive Asiatic black bears were anesthetized for clinical
      procedures, including clinical examination and blood sample collection, and for
      electrocardiographic and echocardiographic procedures. The combination detomidine
      tiletamine-zolazepam, at the dosages of 0.03 mg/kg for detomidine and 1.5 mg/kg
      for tiletamine-zolazepam, proved to be reliable and effective in immobilizing
      Asiatic black bears for a 1-hr handling period for routine clinical procedures.
      Minimal or no respiratory and/or cardiopulmonary adverse side effects were
      observed, even with dosages calculated on the basis of an estimated body weight.
      The respiratory rate, pulse rate, and hemoglobin-oxygen saturation remained
      stable for the entire duration of anesthesia. Cardiac rhythm was always sinusal
      in all animals. Small injection volumes and darts for blowpipe use were utilized
      to minimize tissue damage at the site of injection. Induction and recovery were
      smooth and predictable, and provided for the safety of operators who could
      observe the bears' activities from a safe distance. Furthermore, the availability
      of the alpha2-antagonist atipamezole to counteract the effects of detomidine made
      this anesthetic regimen easily controllable and reversible. Moreover, the
      recovery time can be shortened by intravenous administration of this antagonist
      drug.

PMID- 19110697
TI  - Association of West Nile virus with lymphohistiocytic proliferative cutaneous
      lesions in American alligators (Alligator mississippiensis) detected by RT-PCR.
AB  - West Nile virus (WNV) is known to affect captive populations of alligators and,
      in some instances, cause significant mortalities. Alligators have been shown to
      amplify the virus, serve as a reservoir host, and even represent a source of
      infection for humans. This study describes a cutaneous manifestation of WNV in
      captive-reared American alligators (Alligator mississippiensis), previously
      described as lymphohistiocytic proliferative syndrome of alligators (LPSA), based
      on the findings of gross examination, histopathologic evaluation, WNV antibody
      testing, and WNV reverse transcriptase polymerase chain reaction (RT-PCR). Forty
      alligators with LPSA and 41 controls were examined. There was a significant
      difference (P = 0.01(-21)) in the WNV serostatus between the treatment group
      (100%) and the control group (0%, 95% CI: 0-7.3%). In the treatment group, 97.5%
      (39/40) (95% CI: 92.7-102.3%) of the LPSA skin lesions were positive for WNV via
      RT-PCR. Of the skin sections within the treatment group that had no LPSA lesions,
      7.5% (3/40) (95% CI: 0-15.7%) were positive for WNV. In the control group, all of
      the skin samples were negative for WNV (41/41) (0%; 95% CI: 0-7.3%). The LPSA
      skin lesions were significantly more likely to be WNV positive by RT-PCR when
      compared to control animals (P = 0.07(-20)) and normal skin sections from
      affected animals (P = 0.08(-16)). There was no significant difference in the WNV
      RT-PCR results between control animals and normal skin sections from affected
      animals (P = 0.24). These findings suggest that LPSA is a cutaneous manifestation
      of WNV in alligators.

PMID- 19110698
TI  - Comparison of biomedical evaluation for white-fronted brown lemurs (Eulemur
      fulvus albifrons) from four sites in Madagascar.
AB  - Health and nutritional assessments of wildlife are important management tools and
      can provide a means to evaluate ecosystem health. Such examinations were
      performed on 37 white-fronted brown lemurs (Eulemur fulvus albifrons) from four
      sites in Madagascar. Comparison of health parameters between sites revealed
      statistically significant differences in body weight, body temperature,
      respiratory rate, hematology parameters (white cell count, hematocrit, segmented
      neutrophil count, and lymphocyte count), serum chemistry parameters (aspartate
      aminotransferase, alanine aminotransferase, serum alkaline phosphatase, total
      protein, albumin, phosphorus, calcium, sodium, chloride, and creatinine
      phosphokinase), and nutrition parameters (copper, zinc, ferritin, retinol,
      tocopherol, and 25-hydroxycholecalciferol). Two of 10 lemurs tested were positive
      for toxoplasmosis; none of 10 were positive for Cryptosporidium or Giardia.
      Enteric bacteria and endo- and ectoparasites were typical. Statistically
      different values in hematology and chemistry values probably do not reflect
      clinically significant differences, whereas nutrition parameter differences are
      likely related to season, soil, and forage availability.

PMID- 19110699
TI  - Field anesthesia of golden jackals (Canis aureus) with the use of medetomidine
      ketamine or medetomidine-midazolam with atipamezole reversal.
AB  - Twenty-two free-ranging golden jackals (Canis aureus) were immobilized with a
      combination of 113 +/- 24 microg/kg medetomidine and 2.1 +/- 0.3 mg/kg ketamine
      (M-K) or 88 +/- 16 microg/kg medetomidine and 0.47 +/- 0.08 mg/ kg midazolam (M
      M) by i.m. injection. Induction and recovery times were recorded. Pulse rate,
      respiratory rate, body temperature, systolic and diastolic blood pressures, and
      oxygen saturation were measured. Anesthesia depth indicators were observed. There
      was no significant difference between the M-K and the M-M groups regarding
      induction time (6:14 +/- 1:45 and 7:16 +/- 2:09 min, respectively). Both
      combinations provided safe and effective immobilization for at least 20-30 min.
      Pulse rate was significantly higher in the M-K group. There was no significant
      difference in any other objective or subjective parameter. Following
      administration of atipamezole at five times the dose of medetomidine given, there
      was a significant difference between the two combinations in recovery time; M-K
      jackals were standing within 3:42 +/- 2:17 min and M-M jackals within 8:47 +/-
      4:32 min. Neither of the combinations caused rough or prolonged recovery.
      Subjectively, the M-M group had smoother and less ataxic recovery.

PMID- 19110700
TI  - West Nile virus seroconversion in penguins after vaccination with a killed virus
      vaccine or a DNA vaccine.
AB  - To investigate the serologic response of penguins to West Nile virus (WNV)
      vaccines, four species of exclusively indoor-housed penguins, negative for WNV by
      serology, were evaluated: Humboldt (Spheniscus humboldti), Magellanic (Spheniscus
      magellanicus), Gentoo (Pygoscelis papua), and Rockhopper (Eudyptes chrysoscome)
      penguins. Birds were inoculated with either a killed virus vaccine or a plasmid
      mediated DNA WNV vaccine, and postinoculation serology was evaluated. Both
      vaccines induced seroconversion in all four species, and no adverse reactions
      were noted. Postvaccination serology results varied across species and vaccine
      types. However, in all four species, the killed virus vaccine resulted in a
      greater seroconversion rate than the DNA vaccine and in a significantly shorter
      time period. Additionally, the duration of the seropositive titer was
      significantly longer in those birds vaccinated with the killed virus vaccine
      compared with those vaccinated with the DNA vaccine. A subset of unvaccinated
      penguins serving as negative controls remained negative throughout the duration
      of the study despite the presence of WNV in the geographic locations of the
      study, suggesting that indoor housing may minimize exposure to the virus and may
      be an additional means of preventing WNV infection in penguins.

PMID- 19110701
TI  - Pharmacokinetics of buprenorphine after single-dose subcutaneous administration
      in red-eared sliders (Trachemys scripta elegans).
AB  - Buprenorphine, a mu opioid receptor agonist, is expected to be a suitable
      analgesic drug for use in reptiles. However, to date, dosage recommendations have
      been based on anecdotal observations. The aim of this study was to provide
      baseline pharmacokinetic data in red-eared sliders (Trachemys scripta elegans)
      targeting a plasma level of 1 ng/ml reported effective for analgesia in humans.
      Serial blood samples were taken after subcutaneous injection of buprenorphine,
      and plasma buprenorphine levels were measured by radioimmunoassay.
      Pharmacokinetic parameters of a lower dose (0.02 mg/kg) injected into the
      forelimb were compared with a higher dose (0.05 mg/kg) given in the same forelimb
      as well as a lower dose (0.02 mg/kg) given in the hind limb of the same animals
      with 2 wk between studies. After administration of 0.05 mg/kg in the front limb,
      85% of animals maintained the minimum effective plasma level for 24 hr, while
      only 43% of animals maintained this level after 0.02 mg/kg. After hind limb
      injection at 0.02 mg/kg, maximum plasma concentrations and areas under the
      buprenorphine concentration-time curve were less than 20% and 70%, respectively,
      of values after forelimb injection, consistent with substantial first pass
      extraction by the liver. Furthermore, a secondary rise in the buprenorphine level
      was found after having only a hind limb injection, probably from enterohepatic
      recirculation of glucuronidated drug. In conclusion, buprenorphine dosages of at
      least 0.075 mg/kg s.i.d. should be appropriate for evaluation of analgesia
      efficacy, and front limb administration may be preferable to hind limb
      administration for optimal drug exposure.

PMID- 19110702
TI  - A technique for the capture of free-ranging marsh deer (Blastocerus dichotomus).
AB  - The marsh deer (Blastocerus dichotomus) is an endangered species from the
      marshlands of central South America. Its population has declined in several
      regions due to the loss of available habitat caused by human activities,
      especially the construction of hydroelectric dams. The capture of individual deer
      is critical for research programs and population management. This report
      describes a novel live-capture technique, which uses a helicopter to drive the
      animals into a terrain that restricts their movement such as thick vegetation or
      deep water (60-120 cm in depth). Following confinement, animals are manually
      restrained. The short pursuit time (median = 2 min), low mortality rate (0.82
      3.28%), and the absence of injury to both the capture team and animals suggest
      that this method is appropriate for the safe capture of this species. Body
      temperature correlated with the pursuit time (R2 = 0.15) but was not
      significantly altered with pursuit times <3 min.

PMID- 19110703
TI  - Prevalence of cryptosporidium infection and characteristics of oocyst shedding in
      a breeding colony of leopard geckos (Eublepharis macularius).
AB  - Cryptosporidiosis is an emerging problem in reptile medicine and has been
      associated with a wasting syndrome in leopard geckos (Eublepharis macularius).
      This study determined the prevalence of infection in a breeding colony of leopard
      geckos to be 9.8%. Two groups of 20 geckos, one that was fecal positive for
      oocysts of Cryptosporidium sp., and one, whose individuals were fecal negative at
      the inception of the study, were followed for 2 mo. Fecal samples were tested for
      oocysts every 2 wk, body weights were measured, and a body condition score was
      assigned for each gecko. Selected geckos from these two groups were euthanized
      and necropsied. There were statistically significant differences (P < 0.05)
      between the two groups for mean body weight, mean body condition score, and
      prevalence of infection. Cryptosporidium sp. infection is endemic in this
      breeding colony, and there were a large number of geckos with a subclinical or
      carrier state of infection. These animals continued to be infected with
      Cryptosporidium sp. but gained weight and remained in good body condition. Only
      one gecko in the entire group of 40 was confirmed to be negative for oocysts or
      developmental stages by repeated fecal exams and histopathology. An additional 37
      severely emaciated geckos from the breeding colony were euthanized, and all were
      positive for Cryptosporidium sp. on histopathologic examination of the
      gastrointestinal tract. The results of this study indicate that although some
      animals can recover from a clinical infection, if a gecko is severely wasted, it
      should be euthanized because of the poor prognosis and possible source of
      infection to other geckos.

PMID- 19110704
TI  - Neoplasia in felids at the Knoxville Zoological Gardens, 1979-2003.
AB  - A review of medical records and necropsy reports from 1979-2003 found 40
      neoplasms in 26 zoo felids, including five lions (Panthera leo, two males and
      three females), three leopards (Panthera pardus, two males and one female), one
      jaguar (Panthera onca, female), 11 tigers (Panthera tigris, three males and eight
      females), two snow leopards (Panthera uncia, one male and one female), two
      cougars (Felis concolor, one male and one female), one bobcat (Felis rufus,
      male), and one cheetah (Acinonyx jubatus, female). Animals that had not reached 3
      yr of age or had been housed in the collection less than 3 yrs were not included
      in the study. Neoplasia rate at necropsy was 51% (24/47), and overall incidence
      of felid neoplasia during the study period was 25% (26/103). Neoplasia was
      identified as the cause of death or reason for euthanasia in 28% (13/47) of those
      necropsied. Neoplasms were observed in the integumentary-mammary (n=11),
      endocrine (n=10), reproductive (n=8), hematopoietic-lymphoreticular (n=5),
      digestive (n=3), and hepatobiliary (n=2) systems. One neoplasm was unclassified
      by system. Multiple neoplasms were observed in 11 animals. Both benign and
      malignant neoplasms were observed in all systems except for the hematopoietic
      lymphoreticular systems where all processes were malignant. Of the endocrine
      neoplasms, those involving the thyroid and parathyroid glands predominated (n=8)
      over other endocrine organs and included adenomas and carcinomas. In the
      integumentary system, 63% (7/11) of neoplasms involved the mammary gland, with
      mammary carcinoma representing 83% (6/7) of the neoplasms. The rates of neoplasia
      at this institution, during the given time period, appears to be greater than
      rates found in the one other published survey of captive felids.

PMID- 19110705
TI  - Management of chronic vaginal prolapse in an eastern bongo (Tragelaphus eurycerus
      isaaci).
AB  - A 4.5-yr-old multiparous female eastern bongo (Tragelaphus eurycerus isaaci)
      presented with a prolapsed vagina 4 mo after dystocia and vaginal extraction of a
      large calf. The prolapse was corrected via manual reduction and vulvoplasty
      (Caslick operation). A melengesterol acetate contraceptive implant was placed and
      the bongo was asymptomatic for 6 yr until vaginal prolapse recurrence. The
      vaginal prolapse recurred four times over a 2-yr span and was managed with repeat
      Caslick procedures and several epidural injections using 95% grain alcohol.
      Complications secondary to long-term progestin implant usage, acquired urovagina,
      as well as perineal atony from the alcohol epidurals are believed to have
      contributed to prolapse recurrence. Ovariohysterectomy and vaginoplasty
      ultimately were elected and were curative. According to a survey conducted in
      response to this case, obstetrical issues and female reproductive tract problems
      appear to occur sporadically in captive bongo but are not uncommon.

PMID- 19110706
TI  - Transient type 2 diabetes mellitus in a raccoon (Procyon lotor).
AB  - A privately owned, obese, adult female raccoon (Procyon lotor) presented with
      polyuria, polydipsia, weight loss, and increased appetite. Diabetes mellitus was
      diagnosed based on laboratory findings, including hyperglycemia and glucosuria.
      As a result of the raccoon's age and obesity at the onset of clinical signs, the
      raccoon was thought to have type 2 diabetes mellitus, a diagnosis that was
      supported by paired glucose tolerance tests. Treatment consisted of dietary
      management and daily insulin therapy. The raccoon was gradually weaned off
      insulin with no return of clinical signs, further verifying the characterization
      of type 2 diabetes mellitus.

PMID- 19110707
TI  - Mortalities associated with sepsis, parasitism, and disseminated round cell
      neoplasia in yellow-lipped sea kraits (Laticauda colubrina).
AB  - This case series describes multiple mortalities associated with sepsis,
      neoplasia, and endoparasitism in yellow-lipped sea kraits (Laticauda colubrina)
      at an exhibit aquarium. Over a 2-yr period, the facility kept 42 L colubrina, of
      which 38 died and 19 were suitable for necropsy and histopathology. The common
      clinical syndrome seen in these animals consisted of partial to compete anorexia,
      increased time spent "hauled-out" on land, intermittent regurgitation, chronic
      lethargy, and weight loss. Few animals died without premonitory signs.
      Nutritional support and treatment for presumptive parasitism and sepsis were
      unsuccessful. The mortality seen in this collection of sea kraits could be placed
      into three groups; one group of animals (n=9) died of sepsis secondary to
      necrotizing enteritis or pneumonia; one group (n=6) remained apparently healthy
      for over 1 yr and then died with multifocal granulomas and sepsis; and the last
      group (n=3) died as a result of multicentric lymphoid neoplasia with secondary
      sepsis. The unifying factor in the majority of these cases is the presence of
      septicemia as the proximate cause of death. Based on the clinical picture, it is
      presumed that an immunosuppressive event, such as transport, captivity stress, or
      possible concurrent viral infection, resulted in a septic event and death.

PMID- 19110708
TI  - Eastern equine encephalitis in a captive harbor seal (Phoca vitulina).
AB  - A 31-yr-old male, captive harbor seal (Phoca vitulina) was evaluated for a 48-hr
      period of anorexia followed by the onset of seizures. A prolonged seizure failed
      to respond to anticonvulsant therapy and the animal was euthanized. At necropsy,
      no significant gross lesions were identified. Reverse transcriptase-polymerase
      chain reaction testing of brain samples was positive for eastern equine
      encephalitis virus (EEEV) RNA, and serum was positive for anti-EEEV antibodies by
      plaque reduction neutralization. Histopathologic evaluation revealed severe and
      multifocal encephalitis with leptomeningitis, characterized by neutrophilic
      infiltrates in neuropil, neuronal necrosis, satellitosis, neuronophagia, and
      perivascular cuffs of lymphocytes, macrophages, and neutrophils. Additionally
      there was moderate, multifocal, adrenal cortical necrosis. Immunohistochemical
      staining for EEEV demonstrated viral antigen within necrotic neurons and glial
      cells. Virus was isolated from frozen brain tissue, sequenced for comparison to
      other strains, and determined to be a typical North American strain. EEEV should
      be included as a possible cause of neurologic disease in harbor seals with
      compatible signs located in geographic regions where vector transmission of EEEV
      is encountered.

PMID- 19110709
TI  - Hyperplastic dermatitis associated with acariasis in a siamang (Symphalangus
      syndactylus).
AB  - A 36-yr-old male captive siamang (Symphalangus syndactylus) was evaluated for
      mange in the form of generalized alopecia, flaky skin, and pruritus of 1 mo
      duration. Multiple skin scrapings and biopsies revealed high numbers of
      trombidiiform mites identified as Psorobia (formerly Psorergates) sp. near
      cercopitheci (Acarina: Psorergatidae) based on morphologic characteristics.
      Prolonged repetitive treatment with ivermectin killed the mites and resolved the
      clinical signs. Psorergatid mites should be considered as a cause of dry flaky
      skin in even long-term captive siamangs or other primates. This is the first
      record of psorergatid mites from a primate host in the family Hylobatidae.

PMID- 19110710
TI  - Effects of copper oxide wire particle bolus therapy on trichostrongyle fecal egg
      counts in exotic artiodactylids.
AB  - Four species of artiodactylids (scimitar-horned oryx [Oryx dama]), roan antelope
      [Hippotragus equinus], blackbuck [Antilope cervicapra]), and blesbok [Damaliscus
      pygargus phillipsi]) totaling 13 animals were treated with a one-time 12.5-g dose
      of copper oxide wire particles (COWPs) in a bolus form. Pretreatment, individual
      trichostrongyle fecal egg counts (FECs) were performed using the McMaster
      technique. Individual posttreatment FECs were performed every 7 days for 35 days
      beginning 7 days after bolus administration, and FEC reduction ratios (FECRRs)
      expressed as percentage reductions from pretreatment values were calculated every
      7 days. Mean FECRRs for the 13 animals were 93% +/- 16%, 98% +/- 7%, 91% +/- 28%,
      94% +/- 16%, and 90% +/- 13% at 7, 14, 21, 28, and 35 days posttreatment,
      respectively. These data demonstrate that COWPs in a bolus form were an effective
      method for reducing FEC in exotic artiodactylids. Based on this limited data,
      COWPs show promise as an anthelmintic alternative for exotic artiodactylids in
      zoologic collections.

PMID- 19110711
TI  - The use of total serum proteins and triglycerides for monitoring body condition
      in the Iberian wild goat (Capra pyrenaica).
AB  - Body condition in wild ungulates is traditionally evaluated during the necropsy
      of animals on the basis of the weight of fat stored around or within the vital
      organs, the weight of the organs themselves, and their derived indices. However,
      sometimes it is important to evaluate the nutritional status of the animal by
      means of blood and serum analyses and the interpretation of specific parameters.
      Only in a very few studies is the nutritional status of the animal obtained by
      blood biochemistry and, when obtained, compared with the values for body
      condition obtained by anatomic dissection. In this study, the usefulness of two
      serum parameters, total serum proteins (TSP) and serum triglycerides (ST), was
      assessed in the monitoring of the body condition of Iberian wild goats (Capra
      pyrenaica). In addition, their relationship with the kidney fat index (KFI) and
      its components, kidney mass without fat (KM) and kidney fat (KF) is evaluated. A
      total of 25 wild goats from the Sierra Nevada National Park (southern Iberian
      Peninsula) that were shot by hunters were used in this study. The parameter TSP
      was found to be correlated with KM, and ST was correlated with both KM and KFI.
      Hence, both TSP and ST can be used for monitoring physical condition in wild and
      captive Iberian wild goats.

PMID- 19110712
TI  - Oligodendroglioma in an african lion (Panthera leo).
AB  - A 10-yr-old female lion (Panthera leo) presented for acute onset ataxia and
      weakness with a history of two seizure episodes 6 mo prior to presentation and a
      persistent head tilt for at least 6 mo. Gross necropsy findings included a
      gelatinous mass in the right cerebral hemisphere extending from the frontal to
      the occipital lobes. Histologically, the mass was composed of polygonal cells
      surrounding lakes of mucinous material. These cells had clear cytoplasm, ovoid
      basophilic nuclei, and inapparent cell processes. Immunoreactivity was positive
      for S100 and neuron-specific enolase but negative for glial fibrillary acid
      protein, myelin basic protein, neurofilament triplet, vimentin, and cytokeratin.
      All findings were consistent with an oligodendroglioma. A second neoplasm, a
      pulmonary adenoma, was also iidentified at necropsy.

PMID- 19110713
TI  - Tracheostomy in the giant anteater (Myrmecophaga tridactyla).
AB  - Anesthesia in the giant anteater (Myrmecophaga tridactyla) may be complicated by
      apnea. Although emergent orotracheal intubation may be possible in other species,
      the particular anatomy of the anteater prevents a smooth intubation. A technique,
      developed on a cadaver model, is described for a surgical approach to the trachea
      of the giant anteater that may be used to secure an airway in an anesthetized
      animal under emergent conditions. The approach is complicated by the presence of
      the large paired submaxillary salivary gland and the relatively deep and caudal
      position of the larynx relative to the ramus of the mandible. This procedure,
      however, appears to be a feasible method to achieve endotracheal intubation in
      the anteater.

PMID- 19110714
TI  - Interthalamic hematoma secondary to cerebrovascular atherosclerosis in an aged
      grizzly bear (Ursus arctos horribilis) with primary cardiac schwannoma.
AB  - A 38-year-old intact female Grizzly bear (Ursus arctos horribilis) was evaluated
      for progressive seizure activity, pale mucous membranes, deficient pupillary
      light and menace responses, and irregular shallow respiration. Because of poor
      response to treatment, the animal was euthanized. Gross examination revealed
      abundant hemorrhage in both lateral ventricles; a large, encapsulated mass within
      the rostral interthalamic region; and a well-demarcated, round white mass in the
      apex of the right ventricle. Histologic examination of the interthalamic mass
      revealed a resolving hematoma composed of stratified layers of fibrin and white
      blood cells that was surrounded by a thick fibrous capsule. Most meningeal and
      intraparenchymal blood vessels had multifocal degeneration, fragmentation, and
      fraying of the internal elastic lamina with prominent intimal proliferations and
      plaques. The plaques were formed by small numbers of lipid-laden macrophages
      (foam cells) that were intermixed with occasional lymphocytes and plasma cells.
      The cardiac mass was composed of pallisading and interlacing spindle cells with
      parallel nuclei and abundant, pale eosinophilic cytoplasm consistent with a
      schwannoma.

PMID- 19110715
TI  - Pheochromocytoma in an African warthog (Phacochoerus aethiopicus).
AB  - A 14-yr-old male African warthog (Phacochoerus aethiopicus) with a chronic
      history of intermittent unilateral epistaxis, degenerative osteoarthritis, and
      intermittent weakness in the distal lumbar trunk was evaluated to determine the
      source of epistaxis. No obvious cause was determined, and in light of severe
      osteoarthritis and a holosystolic cardiac murmur, the animal was euthanized. A
      tumor of the right adrenal gland involving the medulla was found at gross
      necropsy. Immunohistochemical staining of the tumor was positive for chromogranin
      and negative for neurofilament protein, which was diagnostic for
      pheochromocytoma. No lesions were observed in either nasal cavity. Systolic,
      diastolic, and mean arterial pressures measured at the time of immobilization
      were elevated when compared with another African warthog immobilized with a
      similar anesthetic regimen. Additionally, the warthog had pronounced serum
      norepinephrine dominance with a norepinephrine:epinephrine ratio of 10.0,
      compared with 0.36 from clinically normal warthogs. Practitioners should consider
      pheochromocytoma when evaluating warthogs or swine for epistaxis.

PMID- 19110716
TI  - Magnetic resonance imaging findings in a red kangaroo (Macropus rufus) with
      otitis.
AB  - Magnetic resonance imaging (MRI) was performed on an adult, male Red kangaroo
      (Macropus rufus) with a history of nonspecific neurologic signs and acute
      discharge from the left ear. MRI revealed findings consistent with otitis and
      possible osteomyelitis of the temporal and mastoid bones. To the authors'
      knowledge, this is the first report of otitis and MRI findings in a kangaroo.

PMID- 19110717
TI  - Sarcoptic mange in wild raccoon dogs (Nyctereutes procyonoides) in Korea.
AB  - Infestation with Sarcoptes scabiei was diagnosed from four wild raccoon dogs
      (Nyctereutes procyonoides) accidentally captured and presented to the Animal
      Health Center in Seoul Grand Park Zoo, Korea. Diagnosis was done by microscopic
      and histologic examination from skin lesions. Sarcoptes scabiei was the only
      species detected from the lesions and characterized by dorsoventrally flattened
      and round bodies, sucker-like pulvilli borne on long nonjointed pretarsi,
      triangular scales and spinelike setae on the dorsum, and three epimeres that are
      chitinous extensions of the coxae of the legs. In addition, infiltration of mast
      cells in the dermis was associated with infestation of the burrowing mite. This
      is the first report of sarcoptic mange in raccoon dogs in Korea. Because heavy
      infestation with S. scabiei was found in all of the captured wild raccoon dogs,
      further work is necessary to develop prophylactic interventions to prevent the
      spread of sarcoptic mange in free-living raccoon dogs in Korea.

PMID- 19110718
TI  - Ketamine and xylazine combinations for short-term immobilization of wild variable
      flying foxes (Pteropus hypomelanus).
AB  - Collection of biological samples from pteropid bats requires chemical restraint
      of the bats to minimize risks to humans and stress to the bat. The effectiveness
      of an intravenous combination of ketamine and xylazine for short-term restraint
      of wild-caught variable flying foxes (Pteropus hypomelanus) in a field situation
      was evaluated. Eight adult male variable flying foxes were injected intravenously
      with 0.1 ml of ketamine and xylaxine containing 5 mg of ketamine and 1 mg of
      xylazine. The mean induction time was 80 +/- 20 sec, and mean immobilization time
      was 26 +/- 10 min. The ketamine-xylazine combination used in this study produced
      effective short-term immobilization of wild variable flying foxes for the
      collection of biological samples.

PMID- 19110719
TI  - Ser484 and Ser494 in REL are the major sites of IKK phosphorylation in vitro:
      evidence that IKK does not directly enhance GAL4-REL transactivation.
AB  - Human c-Rel (REL) is a member of the NF-kappa B family of transcription factors,
      and one of its primary physiological roles is in the regulation of B-cell
      proliferation and survival. Although REL is primarily regulated by cytoplasmic
      nuclear translocation through interaction with I kappa B inhibitors, REL also
      undergoes several posttranslational modifications that have been proposed to
      modulate its transcriptional activation activity. For example, phosphorylation of
      C-terminal sequences of REL has been proposed to increase its transactivation
      activity. In this report, we have used immune complex kinase assays to identify
      Ser484 and Ser494 as the primary sites of IKK alpha- and IKK beta-mediated in
      vitro phosphorylation in the C-terminal transactivation domain of REL. However,
      in cotransfection studies in A293 cells we have failed to detect IKK beta
      mediated phosphorylation of these sites on REL in vivo, nor does IKK beta appear
      to interact with REL in these cells. Ser-to-Ala mutation of Ser484 and Ser494
      does not affect IKK's ability to enhance GAL4-REL transactivation in reporter
      gene assays in A293 cells. We also show that the previously reported effects of
      overexpressed IKK and tumor necrosis factor treatment on GAL4-REL transactivation
      are due to IKK-mediated activation of the endogenous NF-kappa B pathway, which
      increases transcription from kappa B sites in the promoter of a commonly used
      GAL4 expression vector. Taken together, these results do not support a role for
      IKK-mediated phosphorylation as means for regulating the activity of REL in vivo.

PMID- 19110720
TI  - Expression of the p16INK4A/Cdkn2a gene is prevalently downregulated in human
      pheochromocytoma tumor specimens.
AB  - A number of hereditary syndromes have been found to be associated with
      pheochromocytoma development, but there is a paucity of data regarding secondary
      molecular events, such as downregulation of the p16INK4A/Cdkn2a gene (hereafter
      p16), contributing to pheochromocytoma tumorigenesis. Using tissue microarray and
      immunohistochemistry, we evaluated the expression of p16 in 31 pheochromocytoma
      tumor specimens. Our results showed that the p16 gene was expressed at low level
      or even not expressed in all but one specimens [30/31 (96.8%)], indicative of the
      prevalence of p16 downregulation in pheochromocytomas. In contrast, high
      expression of pl6 was observed in the majority of control "normal" specimens [5/7
      (71.6%)]. To further investigate the molecular mechanisms underlying pl6
      downregulation in pheochromocytomas, we used quantitative real-time PCR,
      methylation-specific PCR, and direct DNA sequencing to analyze these specimens
      for potential genetic alterations of the p16 gene. Deletions and aberrant CpG
      methylation of pl6 were identified in 9 (29.0%) and 11 (35.5%) specimens,
      respectively, while one specimen harbored a point mutation, Ala --> Pro at
      residue 20 of P16, and this mutation led to an eightfold decrease in the CDK4
      inhibitory activity of P16. The overall frequency of pl6 genetic alterations is
      67.7%. Taken together, our results demonstrate that reduced expression of pl6 is
      a common event in human pheochromocytomas, and the primary cause for such
      downregulation is inactivating genetic abnormalities in the p16 gene.

PMID- 19110721
TI  - Identification of genes that exhibit changes in expression on the 8p chromosomal
      arm by the Systematic Multiplex RT-PCR (SM RT-PCR) and DNA microarray
      hybridization methods.
AB  - Losses of the p-arm of chromosome 8 are frequently observed in breast, prostate,
      and other types of cancers. Using the Systematic Multiplex RT-PCR (SM RT-PCR)
      method and the DNA microarray hybridization method, we examined the expression of
      273 genes located on the p-arm of chromosome 8 in five breast and three prostate
      human cancer cell lines. We observed frequent decreases in expression of two
      dozen genes and increases in expression of several genes on this chromosomal arm.
      These changes in gene expression of the cell lines were later confirmed by real
      time qRT-PCR. Additionally and more importantly, we found that a number of these
      variations were also observed in the majority of clinical cases of breast cancer
      we examined. These included downregulation of the MYOM2, NP_859074, NP_001034551,
      NRG1, PHYIP (PHYHIP), Q7Z2R7, SFRP1, and SOX7 genes, and upregulation of the
      ESCO2, NP_115712 (GINS4), Q6P464, and TOPK (PBK) genes.

PMID- 19110722
TI  - Temporal gene expression analysis of human coronary artery endothelial cells
      treated with Simvastatin.
AB  - Increasing evidence indicates that the beneficial "pleiotropic" effects of
      statins on clinical events involve nonlipid mechanisms including the modification
      of blood vessel endothelial cell function. However, the involved molecular events
      and pathways are not completely understood. In the present study, Affymetrix
      microarrays were used to monitor the temporal gene expression of human coronary
      artery endothelial cells (HCAEC) treated with simvastatin (Sim) to gain insight
      into statins' direct effects on the endothelial function. We isolated and labeled
      mRNA from HCAEC treated with Sim for 0, 3, 6, 12, 24, and 48 h and hybridized
      these samples to Affymetrix GeneChip HG-U95Av2 to analyze the temporal gene
      expression profile. Out of 12,625 genes present on the HG-U95Av2 GeneChip,
      expression of 5,432 genes was detected. There were 1,475 of 5,432 genes that
      displayed the differential expression compared to baseline (0 h). Fifty-four
      genes were upregulated (< or = twofold) while 61 genes were downregulated ( > or
      = twofold) at 24-48 h after the Sim treatment. Many new target genes and pathways
      modulated by Sim were uncovered. This study indicates that many aspects of the
      pleiotropic effect of Sim on the endothelial cell function can be mediated by
      transcriptional control. Physiological function of 22% of 115 differentially
      expressed genes in Sim-treated HCAEC are currently unknown. These newly
      identified genes could be useful for new mechanistic study and new therapeutic
      modalities. Expressions of 13 out of 18 genes (> 70%) in the cell
      cycle/proliferation control process were significantly inhibited by the Sim
      treatment. CDC25B and ITGB4 gene expressions were validated by RT-PCR and Western
      blotting. Sim's inhibitory effect of on HCAEC growth was confirmed by the
      measurement of [3H]thymidine incorporation into the DNA synthesis. Further in
      depth analysis of this effect may shed light on molecular mechanisms of Sim's
      beneficial inhibition of neointima formation in the atherosclerotic artery
      stenosis.

PMID- 19110724
TI  - Take a family health portrait while enjoying your holiday meal.

PMID- 19110723
TI  - The role of neurotrophins during early development.
AB  - The effects of neurotrophins during the middle and late stages of development are
      well known. It was previously thought that neurotrophins had no role during early
      development, but this is not the case and is the subject of this review article.
      The earliest neurotrophin receptor expressed is that for neurotrophin-3 (NT-3).
      TrkC is detected in the neural plate and is present in the neural tube.
      Initially, the distribution of TrkC is homogenous, but it becomes localized to
      specific regions of the neural tube as the neural tube differentiates. The
      receptor for brain-derived neurotrophic factor (BDNF) and neurotrophin-4/5 (NT
      4/5), TrkB, is detected somewhat later than TrkC in the neural tube where it is
      also differentially localized. In contrast, the NGF receptor, TrkA, was not
      detected during early development. Both NT-3 and BDNF have been shown to have
      effects in vitro during early development. NT-3 caused an increase in neurite
      outgrowth and apoptosis in neural plate explants, and promoted differentiation of
      progenitors into motoneurons. BDNF increased the number of motoneurons in neural
      tube explants. These data suggest that NT-3 and BDNF may play a role during early
      development in vivo.

PMID- 19110725
TI  - Impacting the changing health care environment through collaboration and
      continuing education: the Nursing 2015 initiative example.
AB  - A collaborative initiative among three Ohio health care groups is focusing its
      efforts on change to enhance the practice of nursing. Continuing education
      enables currently practicing nurses to advocate for the advancement of nursing
      and participate in creating change in their practice environments. This
      collaborative model could be used by other states to enhance nursing practice.

PMID- 19110726
TI  - Family presence during resuscitation.
AB  - Family presence during resuscitation is becoming an increasingly well-known and
      sometimes controversial issue among health care providers. Institutional support
      in the form of position statement and guideline development can assist in the
      implementation of a family presence program; however, more research is needed
      into all areas of the practice. Nurses can play an integral role in a practice
      that demonstrates exceptional attention to the needs of the family and,
      ultimately, the patient.

PMID- 19110727
TI  - Developing your career as a nurse educator: the professional portfolio.
AB  - This column describes the elements of a professional portfolio and offers "tips"
      for compiling and presenting the information.

PMID- 19110728
TI  - Transitioning internationally recruited nurses into clinical settings.
AB  - With a growing shortage of nurses, more health care organizations are turning to
      international nurse recruitment as part of their work force strategy. Although
      organizations that recruit internationally invest significant resources, there
      has been little research about the challenges of transitioning international
      nurses into practice environments outside their countries of origin. The purpose
      of the qualitative research presented in this article was to investigate the
      educational and support needs of international nurses from both their perspective
      and that of managers with experience in supervising internationally recruited
      nurses. The authors present educational recommendations and the implications for
      staff development.

PMID- 19110729
TI  - Nurses' knowledge, attitudes, and confidence regarding preventing and treating
      deconditioning in older adults.
AB  - BACKGROUND: This article examines nurses' knowledge, beliefs, attitudes, and
      confidence regarding providing care to prevent and treat deconditioning in
      hospitalized older adults. METHODS: Data were collected from 157 registered
      nurses enrolled in a post-registered nurse, bachelor of science in nursing
      program using a descriptive cross-sectional survey. RESULTS: Nurses' responses
      reflected substantial gaps in their knowledge and theoretical understanding of
      deconditioning, and a strong belief in the need for more education on the
      prevention of it. Levels of confidence in preventing deconditioning in older
      adults were modest, but participants expressed positive attitudes toward nurses'
      role in deconditioning care. Barriers to deconditioning care included lack of
      education, low staffing levels, and a lack of valuing prevention efforts.
      CONCLUSION: This study suggests that it is important to establish gerontology
      continuing education programs with a core component on deconditioning treatment
      and prevention to enhance nurses' knowledge and confidence levels in providing
      care to older adults.

PMID- 19110730
TI  - Rural perceptions of continuing professional education.
AB  - BACKGROUND: This study describes rural health care professionals' perceptions
      about professional isolation and the availability, accessibility, and relevance
      of continuing education. METHODS: Registered nurses (n = 165) and physicians (n =
      59) providing health care services in 26 rural hospitals in two Midwestern states
      participated in the study. RESULTS: Rural health care providers experience
      barriers to accessing relevant continuing education. Although physicians reported
      higher levels of professional isolation than their nurse counterparts,
      professional isolation was identified as a concern by both provider groups.
      CONCLUSIONS: To ensure an adequate supply of knowledgeable and skillful rural
      health care professionals, continuing education specific to the delivery of care
      in rural settings is necessary. Once developed, the continuing education must be
      delivered in a manner that is acceptable and accessible to isolated rural
      providers.

PMID- 19110731
TI  - Competent human research personnel.
AB  - The process of conducting human research is highly regulated, rigorous, detailed
      oriented, potentially harmful, and, hopefully, beneficial. Health professionals
      learn how to critique, design, analyze, and apply human research but have minimal
      education in how to conduct human research. Successful completion of a 24-hour
      course was mandated for research support personnel to enhance the protection of
      human subjects, improve the integrity of data collected, and ensure cost
      effective results. Routine audits demonstrated that the course substantially
      improved the documentation of the informed consent process, source documentation,
      protocol adherence, and regulatory compliance.

PMID- 19110732
TI  - Skin cancer.

PMID- 19110733
TI  - Fluorescence imaging for the demarcation of basal cell carcinoma tumor borders.
AB  - BACKGROUND: Basal cell carcinoma (BCC) is a common malignancy accounting for 80%
      of all nonmelanoma skin cancers. Mohs micrographic surgery (MMS) is considered
      superior to alternative treatments, but the procedure is time consuming and
      costly. Alternative simpler techniques to facilitate accurate tumor demarcation
      are therefore in demand. Fluorescence imaging following application of 5
      aminolevulinic acid is a noninvasive diagnostic technique that gives rapid
      information about the superficial extent of the skin tumor. OBJECTIVE: To
      ascertain whether fluorescence imaging improves the clinical tumor border
      assessment by investigating the consistency between tumor size determination by
      MMS, clinical assessment, and fluorescence imaging. METHODS: Eighteen patients
      with histologically verified nodular BCCs on the face scheduled for MMS were
      included in the study. The night before the surgical procedure, 5-aminolevulinic
      methyl ester cream was applied to the lesion. The following morning, tumor
      borders were determined clinically (clinical size), after illumination with
      Wood's light (fluorescence size), and by the tumor defect left on the skin
      surface following removal of the MMS specimen (Mohs size). RESULTS: The median
      tumor sizes were 93.05 mm2 (Mohs size), 61.05 mm2 (clinical size), and 72.75 mm2
      (fluorescence size). The interclass correlation coefficients between Mohs size
      and fluorescence size was 0.984 and Mohs size and clinical size was 0.752.
      CONCLUSION: Tumor border estimation by fluorescence imaging and clinical
      assessment underestimate the genuine tumor size determined by MMS; however, the
      fluorescence size showed a higher degree of consistency with the Mohs size than
      did the clinical size.

PMID- 19110734
TI  - Moisturizers for the treatment of inflammatory skin conditions.
AB  - The maintenance of normal hydration is an important function of the skin. The
      stratum corneum provides an antimicrobial, antioxidant, and UV barrier and plays
      an integral role in maintaining skin hydration. Environmental factors and disease
      states may compromise the barrier function of the stratum corneum, leading to
      excessively dry skin. Evidence supports the use of moisturizers in the treatment
      of various skin conditions, and a wide variety of these products are currently
      available. The presence of moisturizing agents in a compound, however, may not
      guarantee optimal moisturization effects. Pharmacologic and physiologic (eg,
      concentration, bioavailability, and proper determination of moisturization
      effects), as well as patient-based considerations, can potentially influence the
      effects of moisturizer ingredients. While moisturizers as adjunctive therapy have
      proven benefits in enhancing the management of certain dermatologic conditions,
      the incorporation of moisturizing ingredients into topical treatments may not
      translate into clinical benefit, particularly in the enhancement of skin barrier
      function.

PMID- 19110735
TI  - Imiquimod: a review of basal cell carcinoma treatments.
AB  - Basal cell carcinoma (BCC) is regarded as the most prevalent malignant skin tumor
      in whites. A variety of surgical and nonsurgical interventions are available to
      treat BCC. In recent years, an immune response modifier drug, imiquimod, has been
      approved in treating superficial BCC (sBCC). The objective of the authors was to
      review the published literature to evaluate outcomes such as efficacy, safety,
      and quality of life associated with imiquimod treatment among patients with sBCC.
      A MEDLINE search of the literature was performed to identify studies published
      between January 1, 1995 and March 31, 2008 that evaluated imiquimod efficacy,
      safety, and quality of life in treating BCC. Overall, imiquimod 5% cream was
      associated with increased clinical and histologic clearance among patients with
      sBCC as compared to placebo. The findings from short-term cost effectiveness
      studies suggest that use of imiquimod 5% cream can be more cost-effective than
      surgical interventions such as excision surgery among patients with superficial
      BCC. Future studies evaluating long term cost effectiveness of imiquimod
      treatment are warranted.

PMID- 19110736
TI  - Glucocorticoid-induced osteoporosis in dermatologic practice: a review.
AB  - Systemic glucocorticoids are widely used in dermatologic practice for various
      conditions including connective tissue and immunobullous diseases, vasculitis,
      dermatitis, neutrophilic and other dermatoses, and androgen excess syndromes.
      Long-term use of systemic glucocorticoids has been associated with substantial
      and rapid bone loss, which places patients at increased risk for bone fractures.
      Therefore, bone density measurements and the timely initiation of lifestyle
      modifications and pharmacotherapy are essential for future bone health. The use
      of several Food and Drug Administration-approved agents to prevent and treat
      corticosteroid-induced bone loss has been inconsistent among many specialties. In
      this review, the authors summarize guidelines on the prevention and treatment of
      corticosteroid-induced bone loss published by the American College of
      Rheumatology and supplement these guidelines with descriptions of the latest
      approved pharmacologic therapies and user-friendly flow algorithms. This summary
      should aid dermatologists in providing education and recommendations regarding
      bone health for their patients on systemic glucocorticoids.

PMID- 19110737
TI  - Back to basics: expanding the applicability of the bilobed flap.

PMID- 19110738
TI  - Frontalis muscle plication and imbrication in reconstruction of forehead defects.
AB  - The forehead is a common site for nonmelanoma skin cancer. For medium to large
      sized defects, the primary reconstructive challenge is the paucity of loose
      adjacent donor skin. The authors describe frontalis muscle plication,
      imbrication, and related surgical techniques utilized in reconstructing forehead
      defects. With these techniques, one can significantly reduce wound tension and
      increase the volume of tissue recruited to the defect site as necessary.

PMID- 19110739
TI  - Generalized eruptive keratoacanthomas of Grzybowski treated with isotretinoin.
AB  - Generalized eruptive keratoacanthomas of Grzybowski is a rare condition of
      unknown etiology. The disease is characterized by the abrupt onset of many small
      crateriform papules on the skin and mucous membranes. The authors report of a man
      with multiple eruptive keratoacanthomas of Grzybowski who responded favorably to
      oral isotretinoin therapy. After 2 years of follow-up, a complete regression of
      all lesions was observed, and this rapid clearance under isotretinoin therapy is
      intriguing with regard to the possible etiology of the condition.

PMID- 19110740
TI  - Scarring and persistent erythema after fractionated ablative CO2 laser
      resurfacing.
AB  - The adverse affects of traditional CO2 laser resurfacing have been well reported
      including scarring and hypopigmentation. With the advent of new technology,
      continuous research and development of new devices are being conducted to
      minimize these side effects, yet provide substantial results. The fractionated
      CO2 laser is a recently available product. The authors encountered a case of a 55
      year-old female who presented 9 days posttreatment with a fractionated ablative
      CO2 laser resurfacing with similar side effects as seen with traditional ablative
      CO2 laser resurfacing.

PMID- 19110741
TI  - Basal cell carcinoma arising in a patient with vitiligo.
AB  - Patients with vitiligo are predisposed to solar damage, often suffering from
      actinic keratoses (AK) and squamous cell carcinoma (SCC). However, never have
      these patients been noted to have an increased risk for basal cell carcinoma
      (BCC). In fact, no case reports of these 2 diseases occurring together exist in
      the literature. Here, the authors report a case of basal cell carcinoma arising
      in a patient with vitiligo. This rare occurrence gives question to the nature of
      these tumors and their pathogenesis.

PMID- 19110742
TI  - Videodermatoscopy of lentigo maligna treated with imiquimod.
AB  - Lentigo maligna (LM) is an in situ variant of cutaneous melanoma, which usually
      occurs in sun-damaged skin. Surgical treatment of LM is often difficult and not
      well accepted by patients, as lesions are usually quite large and located on the
      face. Imiquimod 5% cream is a local immune response modifier that has been used
      off-label to treat LM. The authors report of 2 female patients with LM on the
      nose (aged 39 and 48 years) treated with imiquimod 5% cream applied 5 times a
      week for a total duration of 4 months. Videodermatoscopy, a noninvasive
      diagnostic technique, was used to address the diagnosis and to monitor treatment
      response with imiquimod therapy and during follow-up. At the end of the treatment
      period, the lesions had cleared in both patients, with no evident remnants
      confirmed by videodermatoscopy. The patients refused to undergo a control biopsy,
      but complied for a 30-month followed-up period which revealed no evident changes.
      The authors' experience, in agreement with other clinical reports and open
      trials, suggests that topical imiquimod is a valuable treatment option capable of
      leading LM to clinical clearance.

PMID- 19110743
TI  - The use of a surgical hook for alignment in the closure of elliptical excisions.

PMID- 19110744
TI  - Severe cutaneous adverse drug reaction due to fluconazole.
AB  - Fluconazole is a rare cause of severe cutaneous adverse drug reactions. A case of
      a diffuse, exfoliative eruption due to fluconazole is presented. Convincing
      arguments for a diagnosis of both widespread bullous fixed drug eruption and
      toxic epidermal necrolysis are made. The clinical presentation, diagnosis, and
      differentiation of these 2 severe cutaneous acute drug reactions are discussed.

PMID- 19110746
TI  - Lower extremity positioning to relieve tension during surgical reconstruction.
AB  - Surgical wounds on the lower extremity often suffer from prolonged and poor
      healing secondary to decreased blood flow, the effects of gravity, and excessive
      tension placed on the wound. Ensuring perfect apposition of wound edges free of
      tension during the surgical repair can augment this healing process. The authors
      detail a simple and effective technique for improving repairs and outcomes when
      operating on the lower limb by relieving tension on the wound through leg
      positioning.

PMID- 19110745
TI  - Treatment of psoriatic arthritis and recalcitrant skin disease with combination
      therapy.
AB  - Psoriasis and psoriatic arthritis (PsA) are chronic inflammatory disorders.
      Efalizumab targets several T-cell interactions central to psoriasis
      immunopathogenesis. Etanercept and infliximab are antitumor necrosis factor (anti
      TNF) agents that modify the inflammatory and cell-mediated immune responses
      involved in the pathogenesis of psoriasis and PsA. All 3 agents are approved for
      the treatment of plaque psoriasis, and etanercept and infliximab are also
      approved for the treatment of PsA. Twenty patients with psoriasis and PsA have
      been successfully treated with a combination of efalizumab (1 mg/kg/wk) and
      etanercept (25 mg or 50 mg/wk) or infliximab (5 to 6 mg/kg). To date, no serious
      adverse events have been reported. Combination therapy was well tolerated and
      effectively controlled both skin disease and arthritis. The complementary
      activity of efalizumab with an anti-TNF agent is most likely attributable to
      their differing mechanisms of action. Further investigation is warranted.

PMID- 19110747
TI  - No-nonsense dermoscopy self assessment.

PMID- 19110748
TI  - Can topical moisturizers cause cancer?

PMID- 19110749
TI  - A polyomavirus may cause merkel cell carcinoma: implications for immunosuppressed
      states and viral reactivation.

PMID- 19110750
TI  - [Neural mechanisms underlying spasticity].
AB  - Considering the various studies conducted on spasticity, it is quite evident that
      the signs and symptoms of this disorder vary. In some cases of spasticity, spasms
      may be noted. An increase in velocity-dependent stretch reflexes has been
      proposed as a cardinal feature of spasticity. There are 2 possible mechanisms
      underlying increased stretch reflex of spasticity: one is the changes in gamma
      innervations and the other is one the changes in spinal motoneurons. Changes in
      gamma innervations for spasticity are not evident while the muscle are at rest.
      On the other hand, changes are clear in normal subjects during voluntary
      contraction of muscles, but not in sbjects with spasticity. We have discussed the
      changes in membrane properties caused by presynaptic inhibition, reciprocal Ia
      inhibitory function, recurrent inhibition, and autogenic Ib inhibition as the
      other candidate spinal mechanisms for spasticity.

PMID- 19110751
TI  - [Clinical signs, neurophysiological evaluation, and medication of spasticity-
      review].
AB  - Spasticity is usually observed along with paralysis, hyperreflexia, Babinski sign
      and abnormal associated movements associated with dysfunction of central motor
      tracts. In spasticity, exaggeration of the stretch reflex results in increased
      resistance during passive movements. Therefore, spasticity is
      pathophysiologically described as increased muscle tone whose pathognomonic sign
      is decreased passivity. Resistance is more strongly felt during rapid passive
      movements than during slow movements. The resistance felt at the beginning of the
      passive movement abruptly diminishes, which is well known as the clasp-knife
      phenomenon. Another character of spasticity is the distribution of the increment
      in the muscle tone. Not only rigidity, dystonia, and muscle stiffness
      demonstrating increased muscle tone, but also Gegenhalten and contracture of
      joint with normal muscle tone should be differentiated. No neurophysiological
      parameters reflect the degree of spasticity in a strictly parallel fashion.
      However, neurophysiological examinations provide some supportive objective data.
      Surface electromyography is useful to distinguish spasticity from rigidity and
      other conditions with increase muscle tone. The increased amplitude ratio and the
      decreased threshold ratio of the H-wave to the M-wave, and increased amplitude
      and persistence of the F-wave are observed the patients with spasticity. Magnetic
      stimulation is a useful tool to detect corticospinal tract lesions that induce
      leading to spasticity. Transcranial magnetic stimulation, magnetic brainstem
      stimulation, and magnetic spinal motor root stimulation are used to examine the
      entire motor pathway. Since positive correlation between spasticity and
      shortening of the silent period is reported, many investigations including paired
      pulse magnetic stimulation will be necessary for understanding pathophysiology of
      spasticity. Patients with mild and reversible spasticity are usually treated with
      medications. Significant variations exist in the use of these therapies, because
      the treatments often depend on the clinicians' experience. It will be necessary
      to clarify the action mechanism of drugs, to develop new effective drugs, and to
      perform randomized controlled trails so that clinicians can select the optimal
      medication based on evidence.

PMID- 19110752
TI  - [Intrathecal baclofen for severe spasticity].
AB  - Spasticity is often observed in patients with brain or spinal cord injuries.
      Patients with severe spasticity experience considerable difficulty in performing
      the activities of daily living (ADLs). Baclofen is an agonisit at gamma
      aminobutyric acid (GABA) receptors, and is, therefore, a neuroinhibitor, and
      decreases spasticity. However, because of blood-brain-barrier (BBB) sufficient
      concentrations of baclofen do not reach the spinal cord. Intrathecal
      administration of baclofen enables its direct infiltration into the spinal cord,
      and drastically reduce spasticity. In Japan, the government approved intrathecal
      baclofen (ITB) treatment in April, 2006. Thus far we have 40 patients
      administered ITB treatment. Further, we have implanted a pump that delivers
      baclofen in 22 patients who nevertheless require baclofen administration. All
      patients implanted with the pump are satisfied with the reduction in spasticity
      which has improved the performance of activities among wheelchair users and
      facilitates locomotion. In 2 patients, the implants were removed; in 1, the
      reason for the removal infection, and in the other was disruption of catheter. Re
      implantation surgery was performed on both patients and baclofen treatment was
      continued.

PMID- 19110753
TI  - [Use of botulinum neurotoxin for spasticity].
AB  - Spasticity is characterized by increased muscle resistance. It is usually
      associated with muscle weakness or poor motor control. This condition not only
      reduces activities of daily living (ADLs), but also interferes personal hygiere
      and causes caregiuer's difficulty. The use of botulinum neurotoxin (BoNT)
      intramuscular injections is a simple and effective therapy for spasticity. The
      use of BoNT to treat adult patients with spasticity was first reported in 1989,
      since then, using the neurotoxin to treat spasticity became popular in some
      European countries. Now in Japan, BoNT can be used to treat only torticollis,
      blepharospasm and hemifacial spasm because of the legal limitation on its use.
      However, clinical research on the use of BoNT in spasticity caused by stroke is
      presently underway, and an adaptation of the toxin may be available in the near
      future. This article reviews the characteristics of BoNT and the techniques for
      injecting this neurotoxin.

PMID- 19110754
TI  - [Selective peripheral neurotomy and selective dorsal rhizotomy].
AB  - Although non-destructive neuromodulation is becoming popular, ablative
      neurosurgical procedures still play a very important role in the management of
      harmful spasticity. There are 2 major ablative surgeries for spasticity control.
      One is selective peripheral neurotomy that is indicated for focal spasticity such
      as equinus foot and inversion of the foot. Other indications are sciatic
      neurotomy for knee flexion spasticity, musculocutaneous neurotomy for elbow
      flexion spasticity, median nerve neurotomy for finger flexion spasticity and so
      on. The operative invasiveness of such procedures is small with several
      extraordinary advantage. Another well-established method is selective dorsal
      rhizotomy that is indicated for diffuse paraplegic spasticity in cerebral palsy
      children. Recent reports on randomized-controlled studies indicate its long-term
      effectiveness. A less invasive technique and intraoperative neurophysiologic
      assessment is important in selective dorsal rhizotomy to maximize clinical
      benefits and minimize complications. Surgical management of harmful spasticity is
      a very important and rewarding clinical practice, and should be one of the
      standards employed in clinical neurosurgical practice.

PMID- 19110755
TI  - [MicroRNAs in neurobiology].
AB  - MicroRNAs have emerged as a new regulatory factor of gene expression. They
      mediate translational repression or degradation of their target mRNAs by RNA
      interference (RNAi). The expression of each microRNA is tightly regulated in a
      development- and cell-specific manner by various mechanisms such as blockade of
      let-7 family expression by Lin-28 or RNA editing. They also act as regulatory
      switches for development, organogenesis, and cellular differentiation or for
      controlling distinct functions that are required for the maintenance of each
      tissue and cell subtypes. The abundant expression of microRNAs as well as the
      exclusive expression of certain microRNAs in the central nervous system
      highlights their biological importance at all stages of neural development and in
      postmitotic and differentiated neurons. Further, some microRNAs, such as miRNA
      134, and miRNA-132 are localized and are synthesized in part at synaptic sites in
      dendrites to regulate synaptic formation and plasticity. In addition to the
      imparting of basic knowledge about the biogenesis and mechanism of action of
      microRNAs, this review focuses on the recent advances in microRNA studies in
      neurobiology, including the expression pattern of microRNAs in the mammalian
      brain, the role of microRNAs in neural differentiation and maturation, formation
      and plasticity of synaptic connections, and maintenance of neural function such
      as the synthesis of the neurotransmitters in selected neurons. Finally, the
      possible connection between microRNA dysfunction and neurological diseases, and
      future implications for diagnosis, and treatment of defects in human brain
      development and neurodegenerative diseases are discussed.

PMID- 19110756
TI  - [Diagnosis and treatment of adult growth hormone deficiency (aGHD) resulting from
      brain injury--role of aGHD].
AB  - Adult growth hormone deficiency (aGHD) has been widely accepted in
      endocrinological practice. The primary cause of aGHD has been considered to be
      hypothalamic-pituitary lesions. Traumatic brain injury and subarachnoid
      hemorrhage have, however, been emerging as important etiologies of aGHD in recent
      years. Considering the high incidences of these brain injuries and significant
      rate of hypopituitarism in the survivors, the impact of aGHD on public health
      should be much larger than it is generally considered. Patients with aGHD may
      present with reduced lean body mass, increased body adiposity, reduced muscle
      strength and exercise capacity, thin and dry skin, cool, peripheries and impaired
      psychological well-being. The peak GH level should be under 3ng/mL when tested by
      the insulin tolerance, arginine, L-DOPA, or glucagon tests in aGHD patients. The
      peak GH value should be under 9 ng/mL when tested by the GHRP-2 test, this test
      is currently available only in Japan, and is a safe and quick method to assess
      the GH secretory function. A low level of IGF-1 may be an indicator of GHD in the
      presence of hypopituitarism, but a normal IGF-I does not rule out GHD. The GH
      replacement dose should be adjusted according to the normal physiology in order
      to minimize the risk of side effects. GH replacement may influence the metabolism
      of thyroid, glucocorticoid hormone, and increase the requirement of hormones.
      Long-term GH replacement therapy has been reported to improve the morbidity and
      moratlity of aGHD. Although there is no evidence to prove that GH replacement
      increases the risk of recurrence of tumor, de-novo neoplasm, or serious
      cardiovascular disease, the long-term safety of GH replacement should be
      rigorously monitored.

PMID- 19110757
TI  - [Dynamics of cerebral circulation in patients with chronic cerebrovascular
      disease--analysis with multi-channel near infra-red spectroscopic topography plus
      hand grasp as the exercise task].
AB  - We used multi-channel near infra-red spectroscopic topography to evaluate the
      dynamics of cerebral circulation of patients with cerebrovascular disease (CVD).
      The subjects included 17 patients with chronic CVD, while 11 physically
      unimpaired persons served as controls. We used a spectroscopic topography device
      (Hitachi, ETG -100) to determine the topographic values of oxy-Hb, deoxy-Hb, and
      total-Hb in the right and left cerebral hemispheres. Hand grasp for 30 or 60
      second duration was used as the exercise task, and each task was tried twice. In
      the control group, the oxy-Hb values of the left cerebral hemisphere were
      elevated by bilateral hand grasp, while those of the right cerebral hemisphere
      were elevated by left hand grasp. In patients with a lesion in the left cerebral
      hemisphere, oxy-Hb values of the left hemisphere were elevated by the bilateral
      hand grasp, while those of the right hemisphere were elevated only by the healthy
      left hand grasp. When the 30- and 60-second-duration grasp exercises were
      compared, it was found that the oxy-Hb values in the control group corresponded
      to the loading time. In patients with either right or left cerebral lesion, the
      oxy-Hb peak values were lower than those of the control group, while the peak
      values did not show any difference between the 30-and 60-seconds hand grip
      durations themselves. The latency from the start of the grasp to the maximum peak
      of the oxy-Hb value was significantly prolonged in CVD patients as compared with
      that in the control group. As for the relation between the degree of hemiparesis
      and the oxy-Hb values, the value of the oxy-Hb in the left cerebral hemisphere
      during right hand grasp decreases depending on the severity of paralysis induced
      by the left cerebral lesion. The determination of cerebral oxy-Hb values by near
      infra-red spectroscopic topography using exercise test appeared to be useful for
      the evaluation of the dynamic of cerebral circulation in stroke patients.
      Furthermore, the possibility of inducing recovery by the rehabilitation of stroke
      patients, who were in the chronic stage, should be studied.

PMID- 19110758
TI  - [Validity and reliability of the Japanese Version of the Neuropsychiatric
      Inventory-Nursing Home Version (NPI-NH)].
AB  - OBJECTIVE: Neuropsychiatric disturbances are common and burdensome symptoms of
      dementia. Assessment and measurement of neuropsychiatric disturbances are
      indispensable to the management of patients with dementia. Neuropsychiatric
      Inventory (NPI) is a comprehensive assessment tool that evaluates psychiatric
      symptoms in dementia. The Nursing Home Version (NPI-NH) of NPI was developed for
      use in extended care facilitate caring for residents with dementia. We translated
      the NPI-NH into Japanese and examined their validity and reliability. SUBJECTS
      AND METHODS: The subjects were 100 demented inpatients and the nurses in charge
      of them. The Mini-Mental State Examination (MMSE) was conducted with all patients
      and NPI-NH, Cohen-Mansfield Agitation Inventory (CMAI), Cornell Scale for
      Depression in Dementia (CSDD), and Behavior Pathology in Alzheimer's Disease
      (BEHAVE-AD) Rating Scale were conducted with the nurses. We examined validity of
      NPI-NH by comparing its score with the CMAI, CSDD, and BEHAVE-AD. In order to
      evaluate test-retest reliability, NPI-NH was re-adopted to 30 randomly selected
      nurses in charge inpatients by a different examiner 1 week later. RESULTS: The
      frequency score, severity score and occupational disruptiveness score in each NPI
      NH item were significantly correlated with the score of the correspondent item in
      BEHAVE-AD. The agitation score of NPI-NH was significantly correlated with CMAI
      and the depression score of NPI-NH was significantly correlated with CSDD. Test
      retest reliability of the scores of NPI-NH was acceptably high. CONCLUSION: The
      Japanese version of NPI-NH demonstrated sufficient validity and reliability as
      well as the original version of them. It is a useful tool for evaluating
      psychiatric symptoms in demented inpatients.

PMID- 19110759
TI  - [Case of anti P/Q type VGCC antibody positive small lung cell carcinoma that
      occured with subacute cerebellar degeneration, Lambert-Eaton myasthenic syndrome,
      and brainstem encephalitis].
AB  - A 62-year-old man was admitted to our hospital because of rapidly progressive
      dysarthria, truncal ataxia, and gait disturbance. High titers of the ProGRP and
      anti-P/Q-type VGCC antibody were detected in the serum. High accumulation of
      [18F] was detected at the hilus of the left lung on [18F]-FDG-PET scan. A high
      frequency repetitive stimulation test of the median nerve yielded an incremental
      response. On the basis of these findings, a diagnosis of paraneoplastic
      cerebellar degeneration (PCD) and Lambert-Eaton myasthenic syndrome (LEMS)
      associated with small cell lung carcinoma (SCLC) was diagnosed. After intravenous
      immunoglobulin therapy (IVIg), methylprednisolone (m-PSL) pulse therapy, and
      other multidisciplinary concurrent treatments, a partial regression of the SCLC
      and a significant improvement in neurological symptoms were observed. However,
      ataxia relapsed and brainstem encephalitis developed 6 months later. A marginal
      improvement in neurological symptoms was observed with IVIg, m-PSL pulse therapy,
      and intravenous cyclophosphamide pulse therapy (IVCY). SCLC also recurred later.
      We hypothesized that VGCC of the brainstem was damaged by anti-P/Q-type VGCC
      antibody.

PMID- 19110760
TI  - [A 61-year-old female who suffered from herpes simplex encephalitis with expanded
      cerebral lesions on MRI and prolonged clinical course--the diagnostic usefulness
      of PCR using biopsied brain tissue specimens].
AB  - A 61-year-old female developed left hemiparesis after the onset of high fever and
      a consciousness disturbance. Fluid attenuated inversion recovery (FLAIR) MR
      imaging showed high signal intensity lesions in the right temporal lobe,
      cingulate gyrus, and parietal lobe. Encephalitis caused by a herpes simplex virus
      (HSV) infection was suspected and the administration of intravenous aciclovir was
      thus immediately initiated. Her consciousness disturbance rapidly became
      exacerbated; however, the brain lesions progressively expanded to the midbrain
      and left hemisphere. The addition of intravenous high-dose corticosteroids to the
      treatment regimen ameliorated the consciousness disturbance. Although no HSV DNA
      was detected by repeated PCR using cerebrospinal fluid (CSF) specimens, real time
      PCR using a biopsied brain tissue specimens detected HSV type 1 DNA. A
      pathological examination showed destruction of the grey matter and a perivascular
      aggregation of lymphocytes, thus suggesting a diagnosis of necrotizing viral
      encephalitis. Immunohistochemical analysis did not reveal the presence of the HSV
      antigen. Hence, in the present patient failure of PCR or a serological diagnosis
      using CSF specimens can be ascribed to the paucity of viral particles in the
      brain. We therefore concluded that real-time PCR using biopsied brain tissue
      specimens is a novel, sensitive method for detecting causative agents in patient
      with prolonged and undiagnosed encephalitis.

PMID- 19110761
TI  - [Case of defective route finding following right anterior thalamic infarction].
AB  - Defective route finding is a symptom in which an indivisual demonstrates
      inhibility to find the way in the familiar places. This symptom arises from
      lesions at the right parieto-occipital region and the right posterior part of the
      splenium of the corpus callosum. We present a case of defective route finding
      resulting from the right anterior thalamic infarction. A 63-year-old right-handed
      man abruptly presented with difficulty in route finding on his way home. Neither
      spatial neglect nor agnosia was observed with pictures of his house and
      surrounding streets. Although there was an attention disturbance, his activities
      of daily living were spared. Brain MRI revealed a fresh infarction at the right
      anterior nucleus of the thalamus. Single photon emission computed tomography
      using 123I-methyltyrosine showed hypoperfusion at the right parieto-occipital
      region as well as the right thalamus. Neuropsychological tests showed
      visuospatial memory disturbance. To our knowledge, this is the first report of
      defective route finding caused by the right anterior thalamic infarction. The
      right anterior thalamic nucleus might be involved in the visuospatial recognition
      circuit.

PMID- 19110762
TI  - [ 84-year old man with progressive dementia and diffuse leukoencephalopathy
      caused by central nervous system lymphoma].

PMID- 19110763
TI  - [One hundred books which built up neurology (24). Xav. Bchat "General anatomy
      applied to the physiology and medicine" (1801)].

PMID- 19110764
TI  - [Problems in the formation of tuberculosis epidemiological parameters].
AB  - The information obtained from 83 subjects of the Russian Federation on 107,306
      new tuberculosis (TB) cases and TB relapses, recorded for treatment in the
      tuberculous facilities of the Ministry of Health and Social Development of the
      Russian Federation (RF), was analyzed. The completeness and validity of
      indicators and their compliance with Russian Statistics Committee's form 8 were
      studied. RESULTS: among the new TB cases, bacterial discharge was found in 33.3
      +/- 5.2% by microscopy and in 44.9 +/- 8.9% by cultures tests. Decay cavity was
      observed in 42.6 +/- 4.9% of the patients. In the RF, the coverage of patients to
      be tested for Mycobacterium tuberculosis susceptibility was 76.3-83.1% of culture
      positive TB patients. Among the new TB patients, drug resistance (DR) of M.
      tuberculosis to one drug or more was detected in 30.6 +/- 6.7% of those tested
      for drug susceptibility. Multidrug resistance (MDR) was recorded in 11.4 +/- 4.2%
      of the examinees. Among the patients with TB relapses, DR and MDR were found in
      45.4% and 24.7% of the examinees, respectively. The detection rate of
      epidemically dangerous patients in the general health care facilities was as high
      as 12.5%, which is an extremely low value. CONCLUSION: Order No. 50 reporting
      documents needs to be improved for the evaluation of the efficiency of treatment
      and monitoring a tuberculosis epidemic process. It is necessary to follow the
      uniform rules for calculating the values for all RF reporting forms. In
      particular, this concerns the indicators of the prevalence of DR tuberculosis.
      The efficiency of a microbiology study of patients varies in federal districts;
      however it is generally inadequate.

PMID- 19110765
TI  - [To the program on state guarantees to deliver free medical aid to Russia's
      citizens in tuberculosis facilities].
AB  - The program on state guarantees for free medical aid to Russia's citizens in
      tuberculosis facilities shows too high standards for round-the-clock adult
      tuberculosis inpatient beds. Tuberculosis sanatorium beds that are also round-the
      clock stay beds and should be a part of the federal standard are disregarded.
      Hospital-replacing technologies have been inadequately developed in the
      antituberculosis service. There is an excess of pediatric tuberculosis sanatorium
      beds that serve mainly for social, rather than clinical indications.

PMID- 19110766
TI  - [Possibilities of improving the diagnosis and treatment of obstructive pulmonary
      diseases in the Northern Administrative District of Moscow].
AB  - The quality of the diagnosis and treatment of lung diseases was assessed in the
      polyclinics of the Northern Administrative District of Moscow by 2 methods: (1)
      selective examination of 960 case histories of bronchial asthma and chronic
      obstructive pulmonary diseases and (2) questionnaire survey and spirometry of
      2132 patients aged 35 to 75 years who have visited a polyclinic for no
      respiratory diseases. Random check of the case histories revealed a large number
      of diagnostic and medical errors suggesting the undertraining of therapists in
      pulmonology. The performed cycles of educational programs could considerably
      reduce the number of the errors found on recheck. Questionnaire survey and
      spirometry could increase the number of diagnosed cases of chronic lung diseases
      by 10 times.

PMID- 19110767
TI  - [The detection and diagnosis of pulmonary tuberculosis in an investigatory
      isolation ward].
AB  - The purpose of the study was to examine the implication of radiation and
      microbiological methods in the timely detection and diagnosis of pulmonary
      tuberculosis in untried prisoners in an investigatory isolation ward.
      Fluorographic films made in 12,298 convicts were analyzed. Abnormal fluorograms
      were revealed in 14 and 7.7% of the untried prisoners in 2005 and 2006,
      respectively; the changes were tuberculosis-associated in 70.2% of cases.
      Fluorescence microscopy and inoculation were used to carry out sputum tests for
      Mycobacterium tuberculosis in 41.1% of the convicts with abnormal fluorograms and
      complaints about productive cough. Early diagnosis of pulmonary tuberculosis was
      made by microscopy in 14.9% of the prisoners; the diagnosis of tuberculosis was
      verified by the inoculation test in 34.5% of negative microscopy patients. In the
      remaining patients, the diagnosis of tuberculosis was based on X-ray studies and
      the results of treatment.

PMID- 19110768
TI  - [Predictors of the progress of latent tuberculosis to clinically active one].
AB  - The question recently arises as to the diagnosis of tuberculous infection at
      early stages of its development. Tuberculin diagnosis ranks below due to the rise
      ofcomorbidity, including allergic diseases. There is increasing evidence for the
      leading role in the development of this or that type of tuberculous infection. A
      mathematical model was used to identify 5 major of the 35 laboratory parameters
      characterizing the immune profile. The equations of classifying discriminant
      functions derived by the chosen immunological parameters make it possible to
      formalize data strictly and to organize an immunological screening with a high
      degree of accuracy in children with unchanged tuberculin sensitivity, without
      making compound statistical calculations. This fact can meet the requirements of
      immunological prediction of the development of tuberculosis in children.

PMID- 19110769
TI  - [Cytogenetic lesions of bronchial epitheliocytes in patients with pulmonary
      tuberculosis].

PMID- 19110770
TI  - [The specific features of diagnosis of latent small airway obstruction].
AB  - Latent obstruction of the small airway is a preclinical stage of chronic
      obstructive pulmonary disease (COPD), has no specific signs and it is a risk
      factor of respiratory failure. Its mechanism is unknown; it is likely to be
      caused by rearrangement of lung tissue, its increased hydrophicility due to the
      influence of various endogenous factors, which ultimately causes a change in the
      mechanical omechanics. The new sensitive functional integral index (the latent
      small airway obstruction coefficient) has been proposed for timely diagnosis.
      Body plethysmography was used to comparatively study the health status of 152
      women during a gestational period by a special program; of them 66 suffered from
      COPD. It was found that 26 (16.1%) patients who considered themselves healthy had
      latent obstruction of the small airway and there was a considerable increase in
      the number of cases of fetal hypoxic complications.

PMID- 19110771
TI  - [Analysis of the association of the genotype COLIA1 with arterial fluid markers
      in patients with chronic obstructive pulmonary disease and bronchial asthma].

PMID- 19110772
TI  - [Antibiotic-associated diarrheas in phthisiatric care: standardization of their
      diagnosis, treatment, prevention, examination of health care quality].
AB  - The authors propose a phthisiological care-adjusted standard of the diagnosis,
      treatment, prevention of antibiotic-associated diarrhea. They have developed a
      standard-driven algorithm of expert assessment of the quality of medical aid to
      this group of patients.

PMID- 19110773
TI  - [A case of successful treatment for pulmonary tuberculosis in an adult patient
      with cystic fibrosis].

PMID- 19110774
TI  - [Postmortem diagnosis of the major forms of tuberculosis (according to autopsy
      data)].

PMID- 19110775
TI  - Self-promotional, or taking the lead?

PMID- 19110776
TI  - Transcatheter aortic valve implantation--TAVI: so much done...yet so far to go.

PMID- 19110777
TI  - Transcatheter aortic valve implantation--should we do it just because we can?

PMID- 19110778
TI  - "I did not see it coming"...the hard way for the prevention of complications.

PMID- 19110779
TI  - Management of two major complications in the cardiac catheterisation laboratory:
      the no-reflow phenomenon and coronary perforations.

PMID- 19110780
TI  - Rationale and use of antiplatelet and antithrombotic drugs during cardiovascular
      interventions.

PMID- 19110781
TI  - Radiation safety during percutaneous coronary procedures: how to reduce radiation
      exposure and its complications.

PMID- 19110782
TI  - Constructing a checklist for the prevention of complications during percutaneous
      coronary intervention.

PMID- 19110783
TI  - Transcatheter valve implantation for patients with aortic stenosis: a position
      statement from the European association of cardio-thoracic surgery (EACTS) and
      the European Society of Cardiology (ESC), in collaboration with the European
      Association of Percutaneous Cardiovascular Interventions (EAPCI).
AB  - AIMS: To critically review the available transcatheter aortic valve implantation
      techniques and their results, as well as propose recommendations for their use
      and development. METHODS AND RESULTS: A committee of experts including European
      Association of Cardio-Thoracic Surgery and European Society of Cardiology
      representatives met to reach a consensus based on the analysis of the available
      data obtained with transcatheter aortic valve implantation and their own
      experience. The evidence suggests that this technique is feasible and provides
      haemodynamic and clinical improvement for up to 2 years in patients with severe
      symptomatic aortic stenosis at high risk or with contraindications for surgery.
      Questions remain mainly concerning safety and long-term durability, which have to
      be assessed. Surgeons and cardiologists working as a team should select
      candidates, perform the procedure, and assess the results. Today, the use of this
      technique should be restricted to high-risk patients or those with
      contraindications for surgery. However, this may be extended to lower risk
      patients if the initial promise holds to be true after careful evaluation.
      CONCLUSION: Transcatheter aortic valve implantation is a promising technique,
      which may offer an alternative to conventional surgery for high-risk patients
      with aortic stenosis. Today, careful evaluation is needed to avoid the risk of
      uncontrolled diffusion.

PMID- 19110784
TI  - One year results of a new in situ length-adjustable stent platform with a
      biodegradable biolimus A9 eluting polymer: results of the CUSTOM-II trial.
AB  - AIMS: To assess the safety and efficacy of the XTENT customisable drug-eluting
      stent system in the treatment of patients with single long or multiple coronary
      lesions referred for PCI. METHODS AND RESULTS: The CUSTOM-II trial enrolled 100
      patients with de novo lesions in native coronary arteries presenting with either
      single long lesions (n=69) of > or =20 mm length or up to two lesions with a
      total cumulative anticipated stent length of 60 mm of stent (n=31). Patients were
      assessed angiographically at six months, and clinically at one year. Of the 100
      patients enrolled, nine patients experienced a MACE, including five patients
      whose MACE occurred during index hospitalisation (two non-Q-MI, two Q-MI and one
      probable stent thrombosis-related death), and four target lesion
      revascularisations (TLR) at six months. No MACE or stent thrombosis was reported
      between six and 12 months follow-up. In-segment late loss at 6-months was 0.22 +/
      0.28 mm, and in-stent late loss had a range of 0.31 +/- 0.31 mm. CONCLUSIONS:
      The XTENT customisable stent is clinically safe and efficacious as judged by
      angiographic and clinical variables through 12 months follow-up. Further follow
      up and larger randomised comparative studies are needed for its clinical
      positioning.

PMID- 19110785
TI  - Improved renal function and blood pressure control following renal artery
      angioplasty: the renal artery angioplasty in patients with renal insufficiency
      and hypertension using a dedicated renal stent device study (PRECISION).
AB  - AIMS: To evaluate the technical performance of a dedicated renal stent device and
      the clinical outcome. METHODS AND RESULTS: Fifty patients with 55 renal artery
      stenoses (RAS) >70% (66 +/- 12 years, 58% male) were included in this non
      randomised, prospective, multicentre registry. Primary endpoint was the primary
      patency rate at one year defined as > or =70% as determined by duplex ultrasound.
      Major secondary endpoints were procedural success, 30 days MACE rate, the impact
      of the intervention on renal function, blood pressure control, and on B-type
      natriuretic peptide (BNP) level. Procedural success rate was 100% and 30 days
      MACE rate was 0%. Restenosis rate (primary endpoint) and target lesion
      revascularisation rate after 12 months were 3.5% and 1.8%, respectively. After
      one year estimated glomerular filtration rate increased from 51 +/- 26 ml/min to
      61 +/- 28 ml/min (P=0.004). Mean ambulatory blood pressure was reduced from 102
      +/- 14 mmHg to 93 +/- 9 mmHg (P=0.001). Mean daily dose of antihypertensive drugs
      decreased from 3.0 +/- 1.7 to 2.7 +/- 1.4 (P=0.09). Mean BNP decreased from 251
      +/- 282 pg/ml to 188 +/- 219 pg/ml (P=0.046) before discharge. CONCLUSIONS:
      Technical outcome of the tested device is favourable. The impact of the stent
      revascularisation on renal function and blood pressure control was promising.

PMID- 19110786
TI  - Antiplatelet response to the 150-mg maintenance dose of clopidogrel in patients
      with insufficient platelet inhibition after clopidogrel loading for elective
      coronary stent placement.
AB  - AIMS: Our prospective study sought to investigate whether inadequate platelet
      responses to clopidogrel can be corrected by increasing the daily maintenance
      dose from 75 mg to 150 mg. METHODS AND RESULTS: In 117 patients with elective PCI
      after loading with 600 mg clopidogrel, we determined residual platelet
      aggregation in response to 5 micromol/l ADP (RPA) by optical aggregometry after
      the first 75 mg maintenance dose (baseline), and at days 14 and 28. In patients
      with RPA >14% at baseline, we increased the daily dose to 150 mg. Fifty-seven
      additional patients without dose adjustment served as historic control. In 39
      patients with baseline RPA >14%, the increase in maintenance dose to 150 mg
      reduced median RPA significantly (P<0.001) from 24% [interquartile range: 18-32%]
      at baseline to 14% [8-20%1 at 14 days without any further significant change. In
      patients with RPA < or = 14%, who continued on 75 mg clopidogrel, RPA increased
      during the first 14 days by 4.5% (0-14%; P<0.001). At 14 days, the study group
      with selective dose adjustment had a significantly lower RPA than the control
      group without dose adjustment (10.0% [4-20%1 versus 17.0% [9-32%], P<0.001).
      CONCLUSIONS: In patients with a low initial response to clopidogrel, platelet
      inhibition can be improved by increasing the maintenance dose to 150 mg.

PMID- 19110787
TI  - Systematic primary aspiration in acute myocardial percutaneous intervention: a
      multicentre randomised controlled trial of the export aspiration catheter.
AB  - AIMS: It is unclear whether primary aspiration can prevent distal embolisation
      and thereby improve myocardial perfusion in patients presenting with acute
      myocardial infarction (AMI) within 12 hours after onset. METHODS AND RESULTS: At
      24 centres in Europe and India, 249 AMI patients were randomised to primary
      aspiration with the Export aspiration catheter (Medtronic Vascular, Santa Rosa,
      CA, U.S.A.) followed by stenting (N=120) or to conventional stenting without
      primary aspiration (N=129). There were no significant differences between the 2
      groups in baseline characteristics or target lesion TIMI scores. Procedure time
      was 36.7 +/- 18.0 minutes for primary aspiration followed by stenting versus 34.5
      +/- 21.5 minutes for conventional stenting (P=0.08). Debris was obtained by
      primary aspiration from 85.3% of the arteries. The use of a bailout technique was
      significantly lower for primary aspiration than for conventional stenting (5.8%
      vs. 14.7%, P=0.02). For the primary endpoint of the combined rate of myocardial
      blush grade 3 and/or ST-segment resolution >50% to assess myocardial perfusion,
      primary aspiration followed by stenting was superior to conventional stenting
      (85.0% vs. 71.9%, P=0.025). Immediately postprocedure, the rate of myocardial
      blush grade 3 was 35.8% for primary aspiration followed by stenting versus 25.4%
      for conventional stenting (P=0.094). At 60 minutes post procedure, the rate of ST
      segment resolution >50% was 73.5% for primary aspiration followed by stenting
      versus 64.8% for conventional stenting (P=0.218). Primary aspiration was also
      associated with a significantly higher postprocedure corrected TIMI frame count
      than conventional stenting (20 +/- 14.9 vs. 22.8 +/- 14, P=0.02). At 30 days,
      there were no differences between the treatments in the rate of major adverse
      cardiac and cerebral events. CONCLUSIONS: Compared with conventional stenting,
      primary aspiration with the Export aspiration catheter followed by stenting
      improved myocardial reperfusion in AMI patients presenting with TIMI flow grade 0
      to 1. Further study of primary aspiration involving larger numbers of patients is
      warranted to assess its effect on longer-term clinical outcome.

PMID- 19110789
TI  - Titanium-nitride-oxide coated stents versus paclitaxel-eluting stents in acute
      myocardial infarction: a 12-months follow-up report from the TITAX AMI trial.
AB  - AIMS: The aim of this study was to evaluate the effectiveness of titanium-nitride
      oxide (TITANOX)-coated stent and paclitaxel-eluting stent (PES) in patients
      presenting with acute myocardial infarction (MI). METHODS AND RESULTS: A total of
      425 patients presenting with acute non-ST-elevation MI or ST-elevation MI were
      randomly assigned to receive TITANOX-coated stent or PES. The primary end point
      was a composite of MI, target lesion revascularisation (TLR) or death from
      cardiac causes. At 12 months, there was no significant difference between
      patients receiving TITANOX-coated stent or PES in the rates of primary end point
      (10.3% vs. 12.8%, P=0.5), MI (4.2% vs. 8.1%, P=0.1), or TLR (9.3% vs. 7.1%,
      P=0.5), respectively. The incidence of stent thrombosis, defined according to
      Academic Research Consortium classification, was significantly lower in the
      TITANOX group compared to the PES group (0.9% vs. 4.3%, P=0.03). CONCLUSIONS:
      TITANOX-coated stent and PES resulted in comparable clinical outcomes during 12
      months follow-up among patients treated for acute MI.

PMID- 19110788
TI  - Safety in simple versus complex stenting of coronary artery bifurcation lesions.
      The nordic bifurcation study 14-month follow-up results.
AB  - AIMS: The risk of stent thrombosis has been reported to increase with
      percutaneous coronary intervention (PCI) complexity. The present study reports
      the pre-specified secondary endpoint of a 14-month stent thrombosis and major
      adverse cardiac events in patients stented with a simple versus a complex
      bifurcation technique using sirolimus eluting stents (SES). METHODS AND RESULTS:
      A total of 413 patients with a coronary bifurcation lesion were randomised to a
      simple treatment strategy; stenting of main vessel and optional stenting of side
      branch (MV group), or to a complex stenting strategy; stenting of both main
      vessel and side branch (MV+SB group). Mortality data were available in all
      patients and 14-month clinical follow-up data in 395 (96%) of the patients. After
      14 months, the rates of definite, probable and possible stent thrombosis (ARC
      criteria) were 1.0% vs. 0.5%, 1.0% vs. 0% and 0.5% vs. 0% (ns) in the MV and in
      the MV+SB groups, respectively. Rates of MACE were 9.5% in the MV group and 8.2%
      in the MV+SB group (ns). Total death was seen in 2.4% vs. 1.0% and non-PCI
      related myocardial infarction in 2.0% vs. 1.0% in the MV and the MV+SB groups,
      respectively. CONCLUSIONS: After 14 months, two months after recommended
      cessation of dual antiplatelet therapy, the rates of stent thrombosis and major
      adverse cardiac events were low and independent of treatment complexity in
      patients treated with SES for coronary artery bifurcation lesions.

PMID- 19110790
TI  - Procedural and 30-day outcomes following transcatheter aortic valve implantation
      using the third generation (18 Fr) corevalve revalving system: results from the
      multicentre, expanded evaluation registry 1-year following CE mark approval.
AB  - AIMS: To describe the procedural performance and 30-day outcomes following
      implantation using the 18 Fr CoreValve Revalving System (CRS) as part of the
      multicentre, expanded evaluation registry, 1-year after obtaining CE mark
      approval. METHODS AND RESULTS: Patients with symptomatic severe aortic stenosis
      and logistic Euroscore > or =15%, or age > or =75 years, or age > or =65 years
      associated with pre-defined risk factors, and for whom a physician proctor and a
      clinical specialist were in attendance during the implantation and who collected
      the clinical data, were included. From April 2007, to April 2008, 646 patients
      with a mean age of 81 +/- 6.6 years, mean aortic valve area 0.6 +/- 0.2 cm2, and
      logistic EuroSCORE of 23.1 +/- 13.8% were recruited. After valve implantation,
      the mean transaortic valve gradient decreased from 49.4 +/- 13.9 to 3 +/- 2 mmHg.
      All patients had paravalvular aortic regurgitation < or = grade 2. The rate of
      procedural success was 97%. The procedural mortality rate was 1.5%. At 30 days,
      the all-cause mortality rate (i.e, including procedural) was 8% and the combined
      rate of death, stroke and myocardial infarction was 9.3%. CONCLUSIONS: The
      results of this study demonstrate the high rate of procedural success and a low
      30-day mortality in a large cohort of high-risk patients undergoing transcatheter
      aortic valve implantation (TAVI) with the CRS.

PMID- 19110791
TI  - Population characteristics, treatment assignment and survival of patients with
      aortic stenosis referred for percutaneous valve replacement.
AB  - AIMS: An increasing number of patients are referred for percutaneous aortic valve
      replacement (PAVR). Although case studies are available on outcome of selected
      patients, little is known about the demographics, treatment assignment and
      survival of the total referred population. METHODS AND RESULTS: This was a
      prospective observational cohort study. From September 2005 to September 2007,
      100 patients were referred for PAVR of whom 39 underwent PAVR, 14 surgical valve
      replacement (AVR) and three balloon valvuloplasty (PABV). Another 16 refused
      treatment and 28 were no candidate (non severe aortic stenosis [n=11],
      asymptomatic and normal ventricular function [n=3], comorbidity [n=12],
      technically PAVR not feasible [n=2]). The logistic EuroSCORE (Mean, sd) was: 15
      +/- 6% (PAVR), 9 +/- 11% (AVR), 22 +/- 15% (PABV), 25 +/- 14% (refusals) and 17
      +/- 12% (no-candidate). The mean follow-up was 13 months (range 0-30 months).
      Cumulative survival at six months was 97%, 85% and 70%, for PAVR, AVR and
      refusals, respectively. At 12 months, it was 87%, 62% and 40% respectively.
      CONCLUSIONS: Not all patients referred for PAVR finally receive it. Approximately
      15% of the patients received AVR and 30% were considered not eligible. This may
      reflect the lack of sufficient data and need for an improvement in the technology
      in order to offer PAVR to both lower and higher risk patients. Considering risk
      and outcome, it is conceivable that patients who refused treatment could have
      benefited the most from it.

PMID- 19110792
TI  - Direct flow medical percutaneous aortic valve: proof of concept.
AB  - AIMS: This paper reports the technical feasibility of using the Direct Flow
      Medical percutaneous aortic valve (PAV) to treat patients with severe aortic
      stenosis (AS). METHODS AND RESULTS: Eight patients with critical AS underwent
      temporary implantation of the PAV. Two patients received open surgical
      implantation of the device while six patients underwent percutaneous
      implantation. The mean age of these eight patients was 58.1 years, mean pre
      procedural aortic valve area was <0.65 cm2 and pre-procedural gradient was 87.6
      +/- 12.4 mmHg. Procedural success was achieved in seven out of eight patients,
      with a mean post-implantation gradient of 17.9 +/- 9.1 mmHg. There was one death
      related to inferior hypogastric artery dissection. All other patients
      subsequently received open surgical explantation of the PAV and aortic valve
      replacement with a mechanical valve. CONCLUSIONS: The Direct Flow Medical PAV is
      technically feasible and safe to deploy in humans with severe AS and results in a
      significant transaortic gradient reduction.

PMID- 19110794
TI  - Gender-related outcome following percutaneous coronary intervention for ST
      elevation myocardial infarction: data from the Austrian acute PCI registry.
AB  - AIMS: Whether or not primary percutaneous coronary intervention (P-PCI) is
      equally effective and safe in women and men in a real world setting is still a
      matter of debate. The aim of this study was to evaluate the effect of gender on
      in-hospital outcome after P-PCI for ST-elevation myocardial infarction (STEMI) in
      a prospective national registry. METHODS AND RESULTS: This registry includes in
      hospital outcome data from 19 PCI-performing hospitals. During 12 months, 1087
      patients with STEMI were registered (mean age 62 +/- 13 years; 27% women). Women
      were older than men (67 +/- 13 vs. 60 +/- 13 years; p < 0.001) and more often had
      diabetes mellitus (21% vs. 13%; p < 0.001) or cardiogenic shock (15% vs. 9%;
      p=0.004). PCI was performed in 1004 patients (92.4%) and more frequently in men
      than in women (93.9 vs. 88.3%, p=0.002), whereas conservative treatment was more
      often decided in women (9.3% vs 4.3%; p=0.002). No differences were found between
      women and men in primary success rate (TIMI 2+3 flow, 92.9% vs. 93%; p=0.96). On
      univariate analysis, in-hospital mortality was higher in women than in men (13.7%
      vs. 7.2%; p=0.001). On multivariable analysis age, shock, diabetes and TIMI flow
      before PCI remained associated with mortality. CONCLUSIONS: Women have higher in
      hospital mortality following PCI for STEMI. On multivariate analysis age, shock,
      diabetes and TIMI flow, but not gender, were associated with mortality in this
      national register. Older age and more comorbidity are likely to explain the
      higher mortality in female patients undergoing P-PCI.

PMID- 19110793
TI  - Elective implantation of sirolimus-eluting stents for bifurcated and non
      bifurcated unprotected left main coronary artery lesions: clinical outcomes at
      one year.
AB  - AIMS: Recent studies of drug-eluting stents for unprotected left main coronary
      artery (LMCA) disease have been encouraging. We examined the performance of
      sirolimus-eluting stents (SES) for this indication. METHODS AND RESULTS: This
      retrospective study included 228 consecutive patients (mean age = 68 +/- 11
      years, 80.6% men, 26.3% diabetics) who underwent implantation of SES for de novo
      LMCA stenoses. The mean additive and logistic EuroSCOREs were 5.2 +/- 3.9 and 8.2
      +/- 13.2, respectively. The main objective of this study was to measure the rate
      of major adverse cardiac events (MACE), including death, myocardial infarction
      and target lesion revascularisation (TLR) at 12 months. Other objectives were to
      measure the rates of in-hospital MACE and 12-month TLR. Outcomes in 143 patients
      with (BIF+ group), versus 84 patients without (BIF-group) involvement of the
      bifurcation were compared. The pre-procedural percent diameter stenosis (%DS) was
      60.1 +/- 11.2 in the BIF+ versus 54.7 +/- 12.2% in the BIF- group (p=0.008), and
      decreased to 18.0 +/- 9.7 and 13.9 +/- 11.3%, respectively (ns), after SES
      implant. The overall in-hospital MACE rate was 3.5%, and similar in both
      subgroups. The 1-year MACE rate was 14.5% overall, 16.8% in the BIF+ and 10.7% in
      the BIF- subgroup (ns). CONCLUSIONS: SES implants in high-risk patients with LMCA
      stenoses were associated with a low 1-year MACE rate. Stenting of the bifurcation
      was associated with significant increases in neither mortality nor 1-year MACE
      rate.

PMID- 19110795
TI  - Use of the Venture wire control catheter to access complex coronary lesions: how
      to turn procedural failure into success.
AB  - AIMS: To describe the impact of a steerable device on procedural success and
      times. The Venture wire control catheter (VWC-St. Jude Medical, Maple Grove, MN,
      U.S.A.), facilitates wire orientation providing excellent backup support and may
      therefore assist in cases in which conventional approaches have failed. METHODS
      AND RESULTS: We describe all cases in which the VWC catheter was used at our
      institutions. The device was employed after prolonged attempts with standard
      wires had failed. We analysed procedural success and complication rates, as well
      as the impact of this device on procedural times. We evaluated 18 cases. The mean
      time from the first wire attempt to the end of the procedure was 58 minutes.
      Lesion crossing attempts with standard wires were performed for a mean time of 23
      minutes (range 10-45 minutes). The VWC catheter was employed as the last resort,
      leading to procedural success in 14 cases. Lesion crossing with the VWC catheter
      was achieved in a mean time of four minutes (range one to 15 minutes). There were
      no device-related complications. CONCLUSIONS: Our experience shows how the VWC
      catheter can turn procedural failures into successes, significantly impacting
      procedural times in different challenging scenarios. This device may represent an
      extremely useful addition to the interventionalist's armamentarium.

PMID- 19110796
TI  - Quantitative multi-modality imaging analysis of a bioabsorbable poly-L-lactic
      acid stent design in the acute phase: a comparison between 2- and 3D-QCA, QCU and
      QMSCT-CA.
AB  - AIMS: To investigate if three-dimensional (3D) based quantitative techniques are
      comparable to each other and to explore possible differences with respect to the
      reference method of 2D-QCA in the acute phase and to study whether non-invasive
      MSCT could potentially be applied to quantify luminal dimensions of a stented
      coronary segment with a novel bioabsorable drug-eluting stent made of poly-l
      lactic-acid (PLLA). METHODS AND RESULTS: Quantitative imaging data derived from
      16 patients enrolled at our institution in a first-in-man trial (ABSORB)
      receiving a biodegradable stent and who were imaged with standard coronary
      angiography and intravascular ultrasound were compared. Shortly, after stenting
      the patients also underwent a MSCT procedure. Standard 2D-QCA showed significant
      smaller stent lengths (p < 0.01). Although, the absolute measured stent diameters
      and areas by 2D-QCA tend to be smaller, the differences failed to be
      statistically different when compared to the 3D based quantitative modalities.
      Measurements made by non-invasive QMSCT-CA of implanted PLLA stents appeared to
      be comparable to the other 3D modalities without significant differences.
      CONCLUSIONS: Three-dimensional based quantitative analyses showed similar results
      quantifying luminal dimensions as compared to 2D-QCA during an evaluation of a
      new bioabsorbable coronary stent design in the acute phase. Furthermore, in
      biodegradable stents made of PLLA, non-invasive QMSCT-CA can be used to quantify
      luminal dimensions.

PMID- 19110797
TI  - How should I treat a patient with severe and symptomatic aortic stenosis who is
      rejected for surgical and transfemoral valve replacement and in whom a
      transapical implantation was aborted? Percutaneous reconstruction of the right
      ilio-femoral tract with balloon angioplasty followed by the implantation of self
      expanding stents.
AB  - BACKGROUND: A 74 year old male with a history of postero-lateral myocardial
      infarction in 1993 and coronary bypass surgery in 1994 was referred to the
      outpatient clinic in a frail general condition with signs of dyspnoea at rest.
      INVESTIGATIONS: Physical examination, electrocardiography, laboratory tests,
      coronary angiography, abdominal angiography, Echo-doppler, transesophageal echo.
      DIAGNOSIS: Aortic stenosis. MANAGEMENT: Valve replacement.

PMID- 19110799
TI  - Together, we can truly insure the future.

PMID- 19110798
TI  - False lumen stenting: uncommon stent occlusion demonstrated by intravascular
      ultrasound.

PMID- 19110800
TI  - On acquiring decision making skills for endovascular interventions.
AB  - To improve interventional training we propose a staged rational approach for
      decision making and skill acquisition. Education and training for endovascular
      interventions should start to develop the learners' decision-making skills by
      learning from explicit representations of master interventionist's tacit decision
      making knowledge through implementation of the notions of generic interventional
      modules, interventional strategic and tactical designs. We hope that these
      suggestions will encourage action, stimulate dialogue and advance the precision
      of our learning, procedures, practice and patient care.

PMID- 19110801
TI  - "Embargo" on scientific news, a late breaking message from the Ministry of Truth
      (MiniTrue).

PMID- 19110802
TI  - Interventional cardiology highlights of the european Society of Cardiology
      congress, 2008.

PMID- 19110803
TI  - Four-year safety and efficacy of the unrestricted use of sirolimus- and
      paclitaxel-eluting stents in coronary artery bypass grafts.
AB  - OBJECTIVES: Recently, concerns were raised about the relative long-term safety
      and efficacy of drug-eluting stents (DES) in saphenous vein bypass grafts (SVG).
      Our objective was to assess the 4-year relative safety and efficacy of the
      unrestricted use of drug-eluting stents (DES) as compared to bare metal stents
      (BMS) in saphenous vein bypass grafts (SVG). METHODS: Between April 16, 2002 and
      December 2005 a total of 122 consecutive patients were treated with either
      sirolimus- or paclitaxel-eluting stents for saphenous vein graft disease. These
      patients were compared with 128 consecutive patients treated with BMS in the
      immediate preceding period (January 1, 2000 to April 2002). RESULTS: At 4-years
      the cumulative survival rate in the DES group was 77.5% versus 73.0% in the BMS
      group (adjusted HR 1.09; 95% CI 0.63-1.90, Logrank p=0.65). The cumulative
      survival free of major adverse cardiac events (MACE: death, myocardial infarction
      and target vessel revascularisation) was 61.5% vs. 46.8% in the DES and BMS
      groups respectively (adjusted HR 0.77, 95% CI; 0.51-1.16) due to a higher event
      free survival of clinically driven target vessel revascularisation in the DES
      group as compared to the BMS group (81.6% vs. 69.0%; adjusted HR 0.53; 95% CI
      0.27-1.05). CONCLUSIONS: In the present study, the use of DES for SVG PCI was
      associated a similar safety profile and there was a trend towards lower rates of
      TVR and MACE at four years as compared to BMS.

PMID- 19110804
TI  - Characterisation of the "vulnerable" coronary plaque by multi-detector computed
      tomography: a correlative study with intravascular ultrasound-derived
      radiofrequency analysis of plaque composition.
AB  - AIMS: To assess plaque characteristics by multi-detector computed tomography
      angiography in patients with known coronary artery disease and to compare these
      findings with those obtained with intravascular ultrasound-derived radiofrequency
      analysis of plaque composition. METHODS AND RESULTS: By computed tomography,
      lesions were classified on the basis of Hounsfield Units as non-calcified,
      calcified, or mixed. By intravascular ultrasound-derived radiofrequency analysis,
      plaques were classified according to the relative composition of components with
      specific backscatter characteristics (necrotic core, fibrous, fibro-fatty,
      calcium). Thin cap fibroatheroma (defined as necrotic core component >10% without
      evidence of fibrotic cap, calcium >5%, remodelling index >1.05) was considered as
      vulnerable plaque. Seventy-eight plaques were analysed. By computed tomography,
      22 plaques were classified as non-calcified and 56 as mixed. A higher incidence
      of mixed plaques was observed among lesions causing unstable angina and non-ST
      elevation myocardial infarction compared to stable angina (76% vs 38%, p=0.04).
      Plaque composition by radiofrequency analysis was significantly different between
      mixed and non-calcified plaques by computed tomography. The calcium content was
      6.0+/-3.2% vs 2.5+/-1.8% (p=0.001), necrotic core was 14.0+/-6.9% vs 7.5+/-5.6%
      (p=0.03) and fibrous tissue was 59.0+/-7.5% vs 67.0+/-5.9% (p=0.03), for mixed vs
      non-calcified plaques, respectively. Positive, negative predictive value and
      diagnostic accuracy for detection of vulnerable plaque by computed tomography was
      77, 54 and 59%. CONCLUSIONS: Mixed plaque by computed tomography correlates with
      plaque composition as determined by intravascular ultrasound-derived
      radiofrequency analysis. However, the present diagnostic accuracy of computed
      tomography is not high enough to support its use for non invasive detection of
      vulnerable coronary plaque.

PMID- 19110805
TI  - Very late thrombosis in acute myocardial infarction: drug-eluting versus uncoated
      stents.
AB  - AIMS: To evaluate clinical outcomes at 24 months in an unselected population with
      ST-segment elevation myocardial infarction (STEMI) undergoing percutaneous
      coronary intervention (PCI) with drug eluting stents (DES), as compared with bare
      metal stents (BMS). METHODS AND RESULTS: We report our series of 245 consecutive
      patients with STEMI undergoing PCI with DES (n=117) or BMS (n=128) from January
      2003 to August 2005. The primary endpoint was the incidence of major adverse
      cardiac events (MACE) assessed at 24 months. The secondary endpoint was the
      incidence of stent thrombosis according to the Academic Research Consortium
      classification. Propensity score was used to adjust groups for baseline and
      angiographic characteristics. The adjusted rate of the primary endpoint was lower
      in DES as compared with BMS group (15.2% vs 25.7%; HR 0.6 [95% CI 0.3-1.11,
      p=0.1), driven by a significant reduction of TVR (10.1% vs 23.0%; HR 0.4 [95% CI
      0.2-1.01, p=0.03), without any significant difference regarding the composite end
      point of death and recurrent myocardial infarction (7.6% vs 5.4%; HR 1.4 [95% CI
      0.4-5.01, p=0.6). The cumulative incidence of stent thrombosis was 5.3% in DES vs
      0.8% in BMS group (p=0.06). CONCLUSIONS: The use of DES in STEMI was associated
      with lower TVR rates, but no differences were observed about death and myocardial
      infarction at 24 months, as compared with BMS.

PMID- 19110806
TI  - The TandemHeart, percutaneous transseptal left ventricular assist device: a
      safeguard in high-risk percutaneous coronary interventions. The six-year
      Rotterdam experience.
AB  - AIMS: Percutaneous coronary interventions (PCI) in high-risk cardiac patients are
      preferentially referred to specialised myocardial intervention centres (MIC).
      Included in this group are patients with a haemodynamic collapse or high
      likelihood of haemodynamic collapse, either during balloon inflation or with
      acute vessel closure. The TandemHeart, a percutaneous transseptal left
      ventricular assist (PTVA) that can be introduced using standard catheterisation
      laboratory techniques, offers interesting perspectives to reduce procedural
      risks. METHODS AND RESULTS: Between September 2000 to July 2006, The TandemHeart,
      supported the circulation of 23 patients (age: range 46-74, mean 59) admitted to
      our centre for high risk, either emergency or elective, PCI. Successful
      implantation was achieved in 100% of patients. The mean time for implementation
      of circulatory support was 35 minutes (range 16-62). The index PCI was successful
      in all patients except two. A pump flow up to 4L/min was achieved with
      significant reduction of left ventricular filling pressures, pulmonary capillary
      wedge pressure and with significant increase of systemic arterial pressures.
      Duration of support ranged from 1-222 hours (mean 31+/-49.8 hours). Five patients
      died with the TandemHeart in place, four of whom were in irreversible cardiogenic
      shock at admission. Mild to moderate access site bleeding was seen in 27% of
      patients. One patient experienced a loge syndrome of the leg. Core temperature
      (Ct) decreased to <36.5 degrees C in six patients, profound hypothermia (Ct <35
      degrees C) was observed in two patients. There was no technical device failure.
      CONCLUSIONS: The TandemHeart - PTVA provides effective, total left ventricular
      support in very high risk PCI settings. The rate of device related cardiac and
      vascular complications was acceptable.

PMID- 19110807
TI  - Long-term safety and efficacy are observed after implantation of Zotarolimus
      Eluting stent in real-world clinical practice.
AB  - AIMS: Zotarolimus-eluting stents (ZESs) have been shown to be safe and effective
      in randomised trials. We sought to report the clinical outcomes after
      implantation of ZES in real-world clinical practice. METHODS AND RESULTS: ZES
      have been approved for clinical use in Singapore since April 2005. Until December
      31, 2007, a total of 219 patients had undergone implantation of ZES. After
      excluding 11 foreign patients with whom contact was lost, 208 patients (246
      lesions, 305 stents) formed the study cohort. A high-proportion of diabetic
      patients (n=90, 43.3%) was included. Recommended dual antiplatelet therapy was at
      least 3 months (n=147) for patients treated before or 12 months (n=61) after
      January 2007. As of January 2008, the median follow-up duration was 19 months
      (range: 1 to 33 months). There were 10 (4.8%) deaths, including 7 (3.4%) cardiac
      deaths. Myocardial infarction occurred in 11 (5.3%) patients. The numbers of
      patients requiring target vessel revascularisation and target lesion
      revascularisation were 10 (4.8%) and 5 (2.4%) respectively. Using the ARC
      definition, there were two cases of definite stent thrombosis on days 7 and 17,
      and one case of probable stent thrombosis on day 15. CONCLUSIONS: In this real
      world clinical experience, ZES was associated with a low incidence of adverse
      cardiac events at a medium follow-up of one and half years.

PMID- 19110808
TI  - "Gender paradox" in outcome after percutaneous coronary intervention with
      paclitaxel eluting stents.
AB  - AIMS: To evaluate in-hospital and long-term outcome of women undergoing
      percutaneous coronary intervention (PCI) with paclitaxel-eluting stents (PES) as
      compared to men and historic controls treated with bare metal stents. METHODS AND
      RESULTS: Eight-hundred and ten (810) consecutive patients (642 men and 168 women)
      with PES were analysed and also compared with 3,515 patients (2,811 men and 704
      women) with at least one bare metal stent in the three years previous. In the PES
      group, women were significantly older than men (mean age of 68+/-10 vs. 63+/-10
      years, p<0.001), with more diabetes (39.9 vs. 29.7%, p<0.05), smaller treated
      vessels (<2.5 mm in 34.9 vs. 24.8%, p=0.003), more left-anterior descending
      lesions (56.6 vs. 43.2%, p<0.001). More men had multivessel disease (78.8 vs.
      62.5%, p<0,001), dyslipidaemia (73.2 versus 65.4%, p<0.05), smoking habit (74.3
      versus 34.5%, p<0.001) or prior revascularisation (49.7 versus 36.1%, p<0.05).
      Compared to bare metal stents, similar higher risk features were recorded in
      women over time. No gender specific differences in in-hospital outcome were
      observed. At 12 months the rates of cardiac death, acute myocardial infarction
      (AMI) and late thrombosis were respectively 2.0%, 3.7% and 0% in women and 2.1%,
      3.2%, and 1.2% in men (all p=NS). CONCLUSIONS: Albeit with worse baseline
      clinical and angiographic characteristics in women, very high immediate success
      rates and a positive outcome can be achieved in both sexes after PES.

PMID- 19110809
TI  - Early echocardiographic evaluation following percutaneous implantation with the
      self-expanding CoreValve Revalving System aortic valve bioprosthesis.
AB  - AIMS: Although safety and feasibility studies have been published, there are few
      reports dedicated to the echocardiographic evaluation of patients following
      percutaneous aortic valve replacement (PAVR). This report describes the early
      echocardiographic evaluation of patients undergoing PAVR with the CoreValve
      Revalving System. METHODS AND RESULTS: The population consisted of 33 consecutive
      patients with aortic stenosis who underwent successful PAVR. Echocardiograms were
      performed pre-treatment (123+/-110 days prior), post-treatment (6+/-2 days) and
      post-discharge (80+/-64 days). Aortic valve function and left ventricular
      dimensions, systolic and diastolic function were assessed pre- and post
      implantation. The mean age was 81+/-7 years and the mean Logistic Euroscore was
      20+/-12. Following PAVR, the mean transaortic valve gradient decreased (46+/-16
      mmHg pre-treatment vs. 12+/-7 mmHg post-treatment vs. 9+/-5 mmHg post-discharge,
      p<0.001) and the mean effective orifice area increased (0.75+/-0.23 cm2 pre
      treatment vs. 1.97+/-0.85 cm2 post-treatment vs. 1.72+/-0.45 cm2 post-discharge,
      p<0.001). There was no significant change in mean ejection fraction (41+/-12% pre
      treatment vs. 46+/-15% post-treatment vs. 44+/-13% post-discharge, p=0.44).
      Approximately two-thirds of patients had no change in diastolic function at
      follow-up. CONCLUSION: Following implantation, there was a sustained decrease in
      aortic valve gradient and increase in aortic valve area. In addition, the mean
      ejection fraction did not change significantly and in the majority of patients,
      diastolic function was unchanged.

PMID- 19110810
TI  - The "mini-crush technique" for the treatment of coronary trifurcation lesions.
AB  - AIMS: Recent evidence suggest that coronary bifurcation lesions might be treated
      by DES using "the mini-crush technique" with low rate of MACE and restenosis both
      at main and side branches. However, the treatment of a coronary trifurcation
      lesion is more problematic. Here we assess the feasibility of the "mini-crush
      technique" for treating trifurcation lesions. METHODS AND RESULTS: We report on
      the treatment of trifurcation lesions using DES in all branches by the mini-crush
      technique in five consecutive patients (65+/-11.5 years) from December 2004 till
      March 2006. Independently, from the anatomical type of trifurcation, the mini
      crush procedure was performed in all cases. After predilatation of all branches,
      positioning of stents in both side branches at a distance of 1-2 mm proximally to
      the carina of the trifurcation was performed. Side-branch stents were then
      deployed sequentially and crushed at the same time by a balloon positioned in the
      main branch. Afterwards, the main branch stent was advanced to cover the ostium
      of both side branches and deployed. The jailed wire technique was employed in all
      cases, and if possible in both branches. Final triple kissing balloon was
      employed in all cases. The "mini-crush technique" was performed safely in all the
      five patients obtaining an excellent angiographic result at 8.0+/-1.0 months
      follow-up angiography. CONCLUSIONS: The "mini-crush technique" with DES can be
      safely performed giving complete coverage of the ostium of side branches and
      optimising side branch access.

PMID- 19110811
TI  - Comparison of primary angioplasty in rural and metropolitan areas within an
      integrated network.
AB  - AIMS: To compare reperfusion times and in-hospital outcome of patients with STEMI
      treated with primary percutaneous coronary intervention (PCI) in a teaching
      hospital (TH) with or without inter-hospital transfer and in community hospitals.
      METHODS AND RESULTS: We performed a retrospective analysis of 536 patients with
      STEMI treated between January 2005 and December 2006 with primary PCI. Three
      groups were identified. A: 207 patients presented to the TH. B: 121 patients
      transferred to TH from metropolitan area hospitals (MAH). C: 208 patients
      presented in two rural area hospitals (RAH) with primary PCI capability. Baseline
      characteristics were similar. Door-to-balloon (DtB) times were significantly
      (p<0.001) higher in group B (median 120, range 90-180 min) both compared to group
      A (median 60, range 45-90 min) and C (median 73, range 55-99 min). In group B
      79,5% of patients present a DtB > 90 min. In-hospital mortality was 4.9%, 3.3%
      and 4.3% respectively in group A, B and C without significant differences.
      CONCLUSIONS: The expansion of primary PCI to RAH achieves reperfusion delays
      similar to that of patients admitted to TH. Transferred patients present very
      higher DtB when compared to patients treated on-site. In-hospital outcome are
      similar but further studies are warranted.

PMID- 19110812
TI  - Relationship between coronary and renal artery disease and associated risk
      factors in hypertensive and diabetic patients undergoing coronary angiography.
AB  - AIMS: Performing simultaneous renal angiography in patients undergoing coronary
      angiography for suspected coronary artery disease (CAD) is suitable for those who
      have a high probability for renal artery stenosis (RAS), thus better recognition
      of all potential candidates could have paramount importance. METHODS AND RESULTS:
      In a cross sectional study, 260 consecutive hypertensive and/or diabetic patients
      (135 males, 125 females with average age of 57.1 and 57.2 years respectively)
      underwent simultaneous coronary and renal angiography. RAS was identified in 55
      patients (21.2%). Significant RAS (> 50%) was present in 37 patients (14.2%).
      Female sex (P=0.01), older age (62.1+/-10 vs 56.3+/-8.9 years, p=0.001), higher
      serum creatinine level (1.3+/-0.69 vs 0.98+/-0.35 mg/dl p=0.017), reduced
      estimated glomerular filtration rate (eGFR) (58.6+/-25.4 vs 81.8+/-28.1
      ml/min/1.73 m2, p< 0.001), increased levels of intra-arterial systolic blood
      pressure (169.8+/-31.1 vs 155.1+/-28.4 mmHg, p=0.004) and pulse pressure (90.9+/
      26.2 vs 77.5+/-21.9, p=<0.001) during catheterisation, history of hypertension
      alone (p=0.007) or accompanied with diabetes mellitus (DM) (p=0.014) and multi
      vessel CAD (> 2 vessels, p=0.002) were associated with significant RAS in
      univariate analysis and normal coronary arteries was a strong negative predictive
      factor (negative predictive value=95%). There was no significant relationship
      between involved location of coronary arteries, history of DM alone, history of
      dyslipidaemia and smoking with RAS. In multivariate model, female sex [odds ratio
      (OR) 0.3; 95% confidence interval (CI) 0.12-0.80, P=0.016], multivessel CAD (OR
      1.88; 95% CI 1.25-2.83, P=0.002) and reduced eGFR (OR 0.96; 95% CI 0.95-0.99,
      P=0.002) were independent predictors of RAS. CONCLUSIONS: Considering the
      limitations of non-invasive techniques, it seems worthwhile from both diagnostic
      and prognostic standpoints to perform simultaneous renal angiography following
      coronary angiography in patients with multivessel CAD, especially if other
      mentioned risk predictors are also present.

PMID- 19110813
TI  - A primer on the immune system in the pathogenesis and treatment of
      atherosclerosis.
AB  - Atherosclerosis is currently appreciated as a disease with a large inflammatory
      component. The underlying mechanisms, which are uncovered in a rapid pace, are
      greatly interconnected and as such very complex. Nevertheless, for clinicians it
      is important have some degree of insight in these immunologic mechanisms in order
      to interpret the current research advances. The aim of this review is to supply
      clinicians with this knowledge, avoiding too much detail. All the relevant
      immunologic basics will be discussed at first, followed by the immunity related
      theories of atherosclerosis. Finally, current and new immune-modulatory therapies
      will be discussed.

PMID- 19110814
TI  - Comparison of drug-eluting stent cell size using micro-CT: important data for
      bifurcation stent selection.
AB  - AIMS: The size of stent cells is an important design parameter influencing the
      resulting wall coverage and strut positioning of several bifurcation stenting
      techniques. Therefore, we report accurate geometrical information on stent cell
      size of five different stents with the key purpose to assist with stent selection
      for bifurcation lesions. METHODS AND RESULTS: We developed an innovative
      technique to assess cell size with high accuracy based on micro-CT images. In
      addition, the size of the ostium was calculated for several idealised
      bifurcations with a cylindrical main and side branch. The cell circumferences of
      the investigated stents vary substantially, with values between 9.5 and 19.8 mm
      (or an equivalent maximal cell diameter between 3.0 and 6.3 mm). Comparison of
      these cell circumferences with the calculated ostium circumferences shows which
      stents should preferably be used for which bifurcations, as these stents have
      cells that can be sufficiently enlarged by dilating through the side.
      CONCLUSIONS: The cell sizes of the investigated stents differ considerably. This
      should be taken into account when applying a particular bifurcation stenting
      technique. The risk on limited main or side branch patency due to obstructing
      stent struts can be minimised by using the reported data for stent selection.

PMID- 19110815
TI  - Stent migration as a late complication following carotid angioplasty and
      stenting.
AB  - BACKGROUND: A 69-year-old male patient with severe asymptomatic carotid artery
      stenosis was treated percutaneously with implant of two self-expandable stents in
      the right carotid overlapped to each other by 5 mm. The 15-month follow-up colour
      Doppler ultrasound (CDU) revealed a severe stenosis in the target vessel and an
      image suggesting migration of the distal stent. INVESTIGATIONS: Physical
      examination, laboratory test, CDU, carotid angiography, quantitative carotid
      angiography (QCA), brain computed tomography (CT). DIAGNOSIS: Migration of the
      distal stent associated with severe stenosis on the unsupported arterial segment.
      MANAGEMENT: Carotid artery angiography, QCA, antithrombotic therapy, carotid
      artery angioplasty and stenting (CAS).

PMID- 19110816
TI  - Intrepide; Trapidil eluting stent.

PMID- 19110817
TI  - Colorectal screening and molecular genetics.

PMID- 19110818
TI  - Management of Clostridium difficile infection--medical or surgical?

PMID- 19110819
TI  - The role of subintimal angioplasty in the management of arterial disease of the
      lower limb: the North-East of Scotland experience.
AB  - INTRODUCTION: The management of occlusive femoropopliteal disease continues to
      evolve and a definitive strategy remains to be defined. We examine the utility
      ofsubintimal angioplasty (SIA) in our institution. METHODS: A retrospective study
      with predefined end-points, including technical success and primary patency.
      RESULTS: 61 consecutive cases were identified (claudicants n=29 and critical
      ischaemia n=32). Sixty-four percent of occlusions were greater than 10 cm with
      poor run-off (60% with two vessels or less). Technical and physiological success
      was 95% and 79% respectively, with clinical improvement reported by 72%. At a
      mean follow-up of 20 months twelve-month primary patency (assessed clinically,
      with ABPI and selective duplex scanning) was 67% (subgroup analysis: claudicants
      83%, criticals 53%, p=0.02) and morbidity 8% with no limb loss or procedure
      related mortality. CONCLUSION: SIA is an effective procedure for chronic lower
      limb ischaemia with acceptable outcome. Our experience correlates well with
      evidence in the current literature.

PMID- 19110820
TI  - Transhiatal oesophagectomy: techniques, tips and outcomes.
AB  - AIM: To demonstrate our technique and valuable tips for transhiatal
      oesophagectomies. METHOD: 215 patients underwent transhiatal oesophagectomies in
      our unit between 2000 and 2006. RESULTS: In-hospital mortality was 0.9%.
      Anastomotic leak in 12 patients (5.6%). Chyle leak was seen in five patients and
      recurrent nerve neuropraxia in six patients. Iatrogenic splenectomy rate was 6%.
      The median operative time was 151 minutes (range 93-276 minutes). Overall median
      length of hospital stay was 15 days (range 8-95 days). The median survival for
      all patients undergoing transhiatal oesophagectomy for invasive malignancy was
      42.9 months and the one-year and five-year survival were 81% and 48%
      respectively. CONCLUSION: This is a safe and oncologically sound procedure. We
      feel that the tips can be helpful for anyone performing this procedure.

PMID- 19110821
TI  - Mashed-muscle and oxidised regenerated cellulose (Surgicel) hammock: a quick and
      effective way to repair frontal air sinus.
AB  - The authors describe a simple modification of the traditional muscle-packing
      technique to seal exposed frontal air sinus during neurosurgical, ENT and facio
      maxillary trauma and elective procedures. Oxidised cellulose hammock is used to
      effectively hold the muscle piece in place to seal the sinus.

PMID- 19110822
TI  - The impact of new imaging technologies in neurosurgery.
AB  - Neurosurgery has primarily been concerned with resective or ablative techniques
      for the accurate removal of pathological tissue with the minimal disruption of
      surrounding healthy neuronal matter. There have been numerous advances in
      neurosurgery which have aided the neurosurgeon to achieve this aim including the
      development of microsurgical, endoscopic and endovascular techniques. Functional
      neurosurgery has also seen a particular resurgence over the last 15 years with
      the identification of new anatomical targets and clinical indications.
      Technological advances in neuroimaging are providing many new adjuncts to the
      neurosurgeon's armamentarium. Neuronavigation systems and intra-operative imaging
      have improved success in surgical removal of tumours from the central nervous
      system. Accurate epilepsy surgery requires imaging of the epileptogenic zone and
      accurate identification of adjacent eloquent cortex. New imaging modalities such
      as PET, SPECT, and fMRI can now be used in order to reduce neurological deficits
      resulting from surgery. This review highlights some of the major advances in
      neurosurgery and discusses the impact of neuronavigation and functional imaging
      in tumour surgery and epilepsy surgery.

PMID- 19110823
TI  - Prognostic and therapeutic implications of Apc mutations in colorectal cancer.
AB  - The adenomatous polyposis coli gene (Apc) is mutated in most colorectal cancers.
      The multifunctional character of the Apc protein in the regulation of beta
      catenin-mediated gene transcription and cytoskeletal proteins has been well
      described. An important question is how this protein affects the behaviour of
      cells within a tumour and how its mutational status influences the prognosis for
      these tumours. Here we provide an overview of the functions of Apc and examine
      how this information can be used in the prognosis and development of directed
      therapy in colorectal cancer.

PMID- 19110824
TI  - Outcome of laparoscopic colorectal resection.
AB  - It has been nearly two decades since the first laparoscopic colectomy was
      reported. However, the wide application of the procedure in various colorectal
      diseases, particularly colorectal malignancy, has been slow. With the recent
      reports ofoncological outcomes from randomised controlled trials, the oncological
      safety of laparoscopic colectomy has been proven and the long-term outcome is at
      least not inferior to open resection. The application of laparoscopic resection
      should not be regarded as a contraindication against management of colon cancer,
      but instead it appears the preferred treatment when the short-term benefits are
      considered. Regarding rectal cancer, the CLASICC (Conventional versus
      Laparoscopic-Assisted Surgery in Colorectal Cancer) trial showed equal
      oncological outcome in patients who underwent laparoscopic and open resection for
      rectal cancer in a randomised trial. The application of laparoscopic resection
      for rectal cancer should be accepted, though cautions are still needed to
      scrutinise more data from high quality studies.

PMID- 19110825
TI  - Work related aspects of inguinal hernia: a literature review.
AB  - INTRODUCTION: There is a traditional belief that that an inguinal hernia can be
      the result of increased intra-abdominal pressure (IAP) and therefore the
      development of a hernia may be attributed to single strenuous or recurrent
      strenuous events. As a result of this, litigation in this area is frequent.
      METHODS: Medline was searched for English language publications using the
      keywords of 'hernia' or 'hernia AND recurrence' combined with 'work related',
      'physical activity' and 'intra abdominal pressure'. The reference lists of
      appropriate papers identified on the original search were also checked to
      identify all related publications. RESULTS: The search revealed 268 papers of
      which 59 were identified as appropriate to the subject of this review. Although
      publications in this area are scarce, from the literature available to date,
      there is no evidence to support the idea that single or recurrent strenuous
      events or early return to work related activity should result in the formation or
      recurrence of an inguinal hernia. CONCLUSION: Although immediate pain at the time
      of an intensive or recurrent activity followed by a new diagnosis of a hernia
      supports a link between the activity and the hernia occurrence, it is likely that
      a congenital or acquired weakness in the connective tissue or muscles of the
      patient meant that hernia occurrence was almost inevitable. This may have
      significant implications regarding 'work related' hernia and its associated
      litigation.

PMID- 19110826
TI  - Current concepts in female stress urinary incontinence.
AB  - Urinary incontinence is a social burden for up to one-third of the adult female
      population. Careful assessment, a methodical approach and appropriate treatment
      can lead to long-term success in the management of these patients. This article
      gives an outline of current concepts in the evaluation and treatment of stress
      urinary incontinence.

PMID- 19110827
TI  - The recurrent laryngeal nerve in thyroid surgery.
AB  - The recurrent laryngeal nerve (RLN) is an essential nerve for phonation and
      psychosocial interaction. Throughout the annals oflaryngological history, vocal
      cord paralysis has been a well recognised disorder. A rich heritage of scientific
      investigation and research has considered the complexity of vocal cord function,
      laryngoscopic presentation and surgical rehabilitation. Identification and
      preservation of the RLN is the major concern in thyroid surgery. Controversy
      exists regarding the correct pre- and postoperative management in vocal cord
      evaluation. We fully review this topic and challenge, in part, the recent Thyroid
      Clinical Guidelines as published by RCSI.

PMID- 19110828
TI  - Re: Rix TE, Sinha P. Inadvertent parathyroid excision during thyroid surgery.
      Surgeon 2006; 4(6): 339-42.

PMID- 19110829
TI  - Re: Orr D. Surgical training--post-Tooke. Surgeon 2008; 6(2): 67-8.

PMID- 19110830
TI  - Re: Beddy P, Neary P, Crotty P, FBV Keane. Non-seminomatous testicular metastasis
      mimicking acute appendicitis. Surgeon 2006; 4(3): 175-77.

PMID- 19110831
TI  - Cholecystopyloric fistula with gastric outflow obstruction.

PMID- 19110832
TI  - Implicit perceptions of risk and anxiety and pilot involvement in hazardous
      events.
AB  - OBJECTIVE: The aim of the studies was to examine the role of implicit processes
      in aeronautical risk perception and risk taking. BACKGROUND: Aeronautical
      decision making consists of both explicit processes (e.g., comparing options,
      seeking information) and implicit, or intuitive, processes (e.g., immediate
      affective reactions). The present studies utilized a novel methodology, adapted
      from studies in social cognition, to examine the relationship between general
      aviation pilots' implicit reactions toward risk and their involvement in
      hazardous events. METHOD: The Implicit Association Test was used to measure
      pilots' (Study 1: N= 23; Study 2: N= 32) implicit associations between good and
      bad weather conditions and perceptions of risk and anxiety. RESULTS: There was a
      relationship between the pilots' implicit perceptions and previous involvement in
      hazardous aeronautical events as measured by D. R. Hunter's (1995, 2002)
      Hazardous Events Scale. The more weather-related hazardous events the pilots had
      been involved in, the less they associated implicit risk with adverse weather
      (Study 1) and the less implicitly anxious they were toward adverse weather (Study
      2). CONCLUSION: The results show a relationship between implicit associations and
      risk-taking behavior. APPLICATION: Pilots may be involved in risk-taking behavior
      because they perceive less risk in, and are implicitly less afraid of, hazardous
      conditions.

PMID- 19110833
TI  - Investigation of grip force, normal force, contact area, hand size, and handle
      size for cylindrical handles.
AB  - OBJECTIVE: To investigate relationships among grip forces, normal forces, contact
      area for cylindrical handles, handle diameter, hand size, and volar hand area.
      BACKGROUND: Data describing those relationships are needed to predict thrust
      forces and torque capability. METHOD: Additional analyses were performed
      retrospectively on data collected in two previous studies in which participants
      performed maximum grip exertions on cylinders (diameter 38-83 mm) while grip
      force, normal force, and contact area were recorded. The length, width, and volar
      area of the hand were measured. RESULTS: Average total normal force on cylinders
      was 2.3 times greater than grip force measured using a split cylinder (R2 = 65%),
      regardless of the handle diameter examined. The ratio of handle diameter to hand
      length explained 62%, 57%, and 71% of the variances in grip force, normal force,
      and contact area, respectively. Estimated hand area (hand length x width) had a
      linear relationship with measured hand area (using photographs; R2 = 91%),
      although it was 8% less than the measured area. CONCLUSION: This work describes
      the relationship between normal force and grip force independent of handle size
      (for handle diameters from 38 to 83 mm). Normal force and contact area can be
      explained by the interaction between handle size and hand size. Hand area can be
      estimated by hand length times width. APPLICATION: The quantitative relationships
      described in this paper can be used in the design of objects and hand tools to
      determine optimal handle sizes for maximizing grip force, total normal force, or
      contact area.

PMID- 19110834
TI  - Human factors of the confirmation bias in intelligence analysis: decision support
      from graphical evidence landscapes.
AB  - OBJECTIVE: This study addresses the human factors challenge of designing and
      validating decision support to promote less biased intelligence analysis.
      BACKGROUND: The confirmation bias can compromise objectivity in ambiguous medical
      and military decision making through neglect of conflicting evidence and
      judgments not reflective of the entire evidence spectrum. Previous debiasing
      approaches have had mixed success and have tended to place additional demands on
      users' decision making. METHOD: Two new debiasing interventions that help
      analysts picture the full spectrum of evidence, the relation of evidence to a
      hypothesis, and other analysts' evidence assessments were manipulated in a
      repeated-measures design: (a) an integrated graphical evidence layout, compared
      with a text baseline; and (b) evidence tagged with other analysts' assessments,
      compared with participants' own assessments. Twenty-seven naval trainee analysts
      and reservists assessed, selected, and prioritized evidence in analysis vignettes
      carefully constructed to have balanced supporting and conflicting evidence sets.
      Bias was measured for all three evidence analysis steps. RESULTS: A bias to
      select a skewed distribution of confirming evidence occurred across conditions.
      However, graphical evidence layout, but not other analysts' assessments,
      significantly reduced this selection bias, resulting in more balanced evidence
      selection. Participants systematically prioritized the most supportive evidence
      as most important. CONCLUSION: Domain experts exhibited confirmation bias in a
      realistic intelligence analysis task and apparently conflated evidence
      supportiveness with importance. Graphical evidence layout promoted more balanced
      and less biased evidence selection. APPLICATION: Results have application to real
      world decision making, implications for basic decision theory, and lessons for
      how shrewd visualization can help reduce bias.

PMID- 19110835
TI  - Linking task analysis to information relevance.
AB  - OBJECTIVE: The main objective of this study is to present a methodology for
      computing information relevance. BACKGROUND: Relevance is a pervasive term used
      in several domains, such as pragmatics, information science, and psychology.
      Quantifying the relevance of information can be helpful in effective display
      design. Displays should be designed so that the more relevant information is more
      easily accessed. METHOD: This procedure focuses on computing the relevance of a
      piece of information by taking into account three aspects of tasks that use the
      information: the number of different tasks that make use of the information, the
      frequency of occurrence of those tasks, and the criticality of those tasks. The
      methodology can be used to compute the aggregate relevance of a piece of
      information for a particular component of a system or for the entire system. This
      methodology was illustrated using the domain of air traffic control (ATC).
      RESULTS: In support of the validity of the methodology, we were able to confirm
      the value of weather information and traffic information in ATC towers.
      CONCLUSION: The method can be used to derive information relevance, a
      characteristic of information that has implications for display design for any
      domain. APPLICATION: Designers can use information about aggregate relevance to
      design information displays that feature the most relevant information.

PMID- 19110836
TI  - Does content affect whether users remember that Web pages were hyperlinked?
AB  - OBJECTIVE: We determined whether memory for hyperlinks improved when they
      represented relations between the contents of the Web pages. BACKGROUND: J. S.
      Farris (2003) found that memory for hyperlinks improved when they represented
      relations between the contents of the Web pages. However, Farris's (2003)
      participants could have used their knowledge of site content to answer questions
      about relations that were instantiated via the site's content and its hyperlinks.
      METHOD: In Experiment 1, users navigated a Web site and then answered questions
      about relations that were instantiated only via content, only via hyperlinks, and
      via content and hyperlinks. Unlike Farris (2003), we split the latter into two
      sets. One asked whether certain content elements were related, and the other
      asked whether certain Web pages were hyperlinked. Experiment 2 replicated
      Experiment 1 with one modification: The questions that were asked about relations
      instantiated via content and hyperlinks were changed so that each question's
      wrong answer was also related to the question's target. RESULTS: Memory for
      hyperlinks improved when they represented relations instantiated within the
      content of the Web pages. This was true when (a) questions about content and
      hyperlinks were separated (Experiment 1) and (b) each question's wrong answer was
      also related to the question's target (Experiment 2). CONCLUSION: The accuracy of
      users' mental representations of local architecture depended on whether
      hyperlinks were related to the site's content. APPLICATION: Designers who want
      users to remember hyperlinks should associate those hyperlinks with content that
      reflects the relation between the contents on the Web pages.

PMID- 19110837
TI  - Assessing the effectiveness of interactive media in improving drowsy driver
      safety.
AB  - OBJECTIVE: This study investigated the possibility of using interactive media to
      help drowsy drivers wake up, thereby enabling them to drive more safely.
      BACKGROUND: Many studies have investigated the negative impacts of driver
      drowsiness and distraction in cars, separately. However, none has studied the
      potentially positive effects of slightly interactive media for rousing drowsy
      drivers to help them drive more safely. METHOD: In a 2 (drowsy vs. nondrowsy
      drivers) x 2 (passive vs. slightly interactive voice-based media) x 2 (monotonous
      vs. varied driving courses) study, participants (N = 79) used a driving simulator
      while interacting with a language-learning system that was either passive (i.e.,
      drivers merely listen to phrases in another language) or slightly interactive
      (i.e., drivers verbally repeat those phrases). RESULTS: (a) Drowsy drivers
      preferred and drove more safely with slightly interactive media, as compared with
      passive media. (b) Interactive media did not harm nondrowsy driver safety. (c)
      Drivers drove more safely on varied driving courses than on monotonous ones.
      CONCLUSION: Slightly interactive media hold the potential to improve the
      performance of drowsy drivers on the primary task of driving safely. APPLICATION:
      Applications include the design of interactive systems that increase user
      alertness, safety, and engagement on primary tasks, as opposed to systems that
      take attentional resources away from the primary task of driving.

PMID- 19110838
TI  - Blending speech output and visual text in the multimodal interface.
AB  - OBJECTIVE: Simultaneous reading and listening with a redundant display of visual
      text with speech output was investigated to determine how variations in verbal
      working memory capacity and content complexity affected comprehension.
      BACKGROUND: Previous work has found some evidence of a benefit for displays that
      blend speech and visual text; content complexity and verbal working memory
      capacity are likely to significantly determine this benefit. METHOD: In the
      experiment reported here, a multimodal display of e-mail messages was compared
      with speech output alone and with a purely visual display. Comprehension of the
      messages was examined in relation to verbal working memory capacity and the
      complexity of the messages. Thirty-two users participated in the study, which
      used a repeated measures design. RESULTS: The data show that the multimodal
      interface did not affect comprehension relative to a purely visual interface,
      even when the content was more complex, although it did improve the comprehension
      of complex information relative to a purely auditory interface. Lower-capacity
      participants were neither especially advantaged nor disadvantaged by the
      multimodal interface. Participants expressed a marked preference for the
      multimodal display of the more complex sentences. CONCLUSION: The experiment
      suggests that a redundant multimodal display will neither assist nor disrupt
      understanding when compared with a purely visual display, but it will assist
      understanding of complex content when compared with speech output alone.
      APPLICATION: Redundant displays of visual text and speech have potential
      application in multitask situations, in multimedia presentations, and for devices
      with small screens.

PMID- 19110839
TI  - Multisensory integration with a head-mounted display: sound delivery and self
      motion.
AB  - OBJECTIVE: We tested whether the method of sound delivery affects people's
      ability to integrate information from multiple modalities when they are walking
      and using a head-mounted display (HMD). BACKGROUND: HMDs increasingly support
      mobile work. Human operators may benefit from auditory support when using an HMD.
      However, it is unclear whether sound is better delivered publicly in free field
      or privately via earpiece and what the effect of walking is. METHOD: Participants
      identified mismatches between sounds and visual information on an HMD.
      Participants heard the sounds via either earpiece or free field while they either
      sat or walked about the test room. RESULTS: When using an earpiece, participants
      performed the mismatch task equally well whether sitting or walking, but when
      using free-field sound, participants performed the task significantly worse when
      walking than when sitting (p = .006). CONCLUSION: The worse performance for
      participants using free-field sound while walking may relate to spatial and
      motion inconsistencies between visual events on the head-referenced HMD and
      auditory events from world-referenced speakers. Researchers should more
      frequently examine the effect of self-motion on people's ability to perform
      various multisensory tasks. APPLICATION: When multisensory integration tasks are
      performed with an HMD and free-field delivery of sound, as may happen in
      medicine, transportation, or industry, performance may suffer when the relative
      location of sound changes as the user moves.

PMID- 19110840
TI  - Accessibility of radiology equipment for patients with mobility disabilities.
AB  - OBJECTIVE: The purpose was to evaluate accessibility of typical radiology
      platforms by participants with mobility disabilities. BACKGROUND: These patients
      have difficulty using radiology equipment and have an increased risk of falling.
      METHODS: This field study evaluated three common types of radiology platforms - X
      ray, computed tomography (CT) scan, and fluoroscopy - by 20 patients/participants
      with mobility impairments who used walking aids. The participants were required
      to get onto the equipment, simulate a typical radiological procedure, and get
      off. Each participant then watched a video of his or her own session and answered
      questions. Four researchers independently reviewed the videotapes and identified
      accessibility and safety barriers. RESULTS: Overall, the CT scan platform was the
      easiest to use and the fluoroscopy platform the most difficult, primarily because
      of platform height differences. Sitting up on the Xray table was rated as
      difficult by most participants, primarily because of a lack of hand-holds and the
      surface pad not being fixed in place. Maintaining a position on the fluoroscopy
      platform while it rotated from horizontal to vertical was difficult and
      frightening for most participants. CONCLUSION: Some radiology platforms are
      difficult to use and are perceived to be less safe for patients with mobility
      disabilities. The interaction of patient disability and equipment design can
      impose substantial physical demands on medical personnel. Recommendations for
      improved design are provided to enhance radiology platform accessibility and
      safety. APPLICATION: The findings may be applicable to the design of a wide range
      of medical patient platforms.

PMID- 19110841
TI  - Critical roles for distance, task, and motion in space perception: initial
      conceptual framework and practical implications.
AB  - OBJECTIVE: A conceptual framework of visual space perception is proposed.
      BACKGROUND: Prior studies suggest that the processes underlying space perception
      depend on viewing distance, the nature of a task, and the presence and nature of
      motion. METHOD: Evidence from neuropsychological, neuroimaging, and behavioral
      studies is reviewed. RESULTS: A preliminary conceptual framework of space
      perception is proposed in which three critical factors of distance, task, and
      motion represent different dimensions. Different locations within the framework
      represent the involvement of different underlying processes. At one extreme,
      indirect perception underlies a stationary observer's perceptual judgments of
      stationary objects in far space. At the other extreme, direct perception
      underlies a moving observer's actions involving moving objects in near space.
      Between these extremes, both processes are utilized and allow for flexibility in
      human performance. CONCLUSIONS: Prior studies of space perception should be
      reevaluated based on viewing distances employed, the nature of the tasks, and the
      presence and nature of motion. Future studies of space perception should
      manipulate these variables. APPLICATION: If, as proposed by the framework,
      observers use different underlying mechanisms to perceive near and far spaces and
      to perform different types of tasks, it becomes important to identify the limits
      of such mechanisms and to design technologies to accommodate those limits. For
      example, collision-avoidance warning systems may have to utilize different
      criteria for providing warnings at near versus far headways. Further study of the
      proposed framework will help improve the design of such technologies.

PMID- 19110842
TI  - On the portability of computer-generated presentations: the effect of text
      background color combinations on text legibility.
AB  - OBJECTIVE: The aim of our study was to investigate which text-background (TB)
      color combinations improve legibility and pleasantness of texts either presented
      on a computer screen or projected on a wider surface. BACKGROUND: Our work stems
      from the observation that multimedia presentations, even those by professionals
      in visual disciplines, are often spoiled by illegibility, which affects
      readability and the pleasantness of attending to such presentations. METHODS: We
      investigated this problem through three experiments. Experiment 1 assessed the
      best TB color combinations in slides presented on a laptop. Experiment 2 verified
      the correlation between legibility and pleasantness for TB presentations.
      Experiment 3 investigated the legibility of a slide projected on a wide screen in
      different room lighting conditions. In all experiments participants expressed a
      rating score for stimulus legibility or pleasantness. RESULTS: Experiments 1 and
      3 showed that it is best to have a dark text on a light background for both
      displayed and projected texts. Experiment 2 showed that pleasantness is tightly
      correlated with legibility, though legibility depends on contrast between text
      and background. CONCLUSIONS: Our findings are not in complete agreement with the
      literature concerning legibility of text displayed on a computer screen, and they
      are in contrast with the common belief that for projection purposes it is best to
      have a light text on a dark background. APPLICATIONS: Some practical rules on
      combining TB colors are given to enhance the legibility of presentations,
      especially important for the legibility of projected texts.

PMID- 19110843
TI  - Effects of memory rehearsal on driver performance: experiment and theoretical
      account.
AB  - OBJECTIVE: We report an experiment and a theoretical analysis concerning the
      effects of an exclusively cognitive task, specifically a memory rehearsal task,
      on driver performance. BACKGROUND: Although recent work on driver distraction has
      elucidated the sometimes significant effects of cognitive processing on driver
      performance, these studies have typically mixed cognitive with perceptual and
      motor processing, making it difficult to isolate the effects of cognitive
      processing alone. METHOD: We asked participants to drive in a driving simulator
      during only the rehearsal stage of a serial-recall memory task while we measured
      their ability to maintain a central lane position and respond to the illumination
      of a lead vehicle's brake lights. RESULTS: Memory rehearsal significantly
      affected drivers' steering performance as measured by lateral deviation from lane
      center, and it also significantly affected drivers' response time to the braking
      stimulus for the higher load memory task. CONCLUSION: These results lend support
      to a theoretical account of cognitive distraction provided by threaded cognition
      theory in terms of a cognitive bottleneck in procedural processing, and they also
      suggest that consideration of task urgency may be important in accounting for
      performance trade-offs among concurrent tasks. APPLICATION: The experiment
      augments the current understanding of cognitive driver distraction and suggests
      that even exclusively cognitive secondary tasks may sometimes affect driver
      performance.

PMID- 19110844
TI  - Warning reliability and driver performance in naturalistic driving.
AB  - OBJECTIVE: This study examines how naturalistic driving performance is influenced
      by the perceived reliability of an in-vehicle warning system using a unique
      measure of perceived reliability. BACKGROUND: Prior studies of warning
      reliability conducted in simulator and test-track experiments demonstrate that
      the objective reliability of a warning can influence a driver's responsiveness to
      that warning. METHODS: Driver responses to lateral drift warnings (LDWs) were
      examined to determine if the latency to initiate a corrective steering response
      was related to the subjective reliability of prior system performance. An
      operational definition of subjective reliability was developed based on measures
      of the proportion of LDWs responded to by a steering correction in the preceding
      24-hr period - the day proportion. Age, gender, weather condition, light level,
      road class, weekday status, and day proportion were used to model correction
      latency in a linear model. RESULTS: A main effect of day proportion was found,
      suggesting that reaction time to respond decreases by about 375 ms as the day
      proportion increases from 0 to 1. CONCLUSION: The study illustrates a method of
      quantifying subjective reliability and performance using naturalistic data. The
      results suggest that latency to make a steering correction is inversely related
      to the perceived reliability of the warning system in the 24 hr preceding the
      warning. APPLICATION: The results have direct application to the method of
      assessing the efficacy of in-vehicle collision warning systems, suggesting that
      use of a perceived reliability measure may better predict a driver's disposition
      to respond to a warning.

PMID- 19110845
TI  - Good care right to the end.

PMID- 19110846
TI  - On a mission to make nursing research more user-friendly.

PMID- 19110847
TI  - Terms of endearment.

PMID- 19110848
TI  - In a time of change.
AB  - A combination of restructuring and cutbacks threatens nursing posts in Northern
      Ireland.

PMID- 19110849
TI  - Sharing the caring.
AB  - Northern Ireland has led the way in integrated services since the 1970s, while
      elsewhere in the UK such services are still in their infancy.

PMID- 19110850
TI  - Take a breath.
AB  - New research suggests some inhaled agents can pose a risk to people with chronic
      obstructive pulmonary disease. But the alternatives may not be as effective in
      treating the disease.

PMID- 19110851
TI  - Power to the people.
AB  - Nurses are being encouraged to join their Local Involvement Network to hold NHS
      and social care services to account.

PMID- 19110852
TI  - A race for men too.

PMID- 19110853
TI  - Nursing students' views on learning opportunities in primary health care.
AB  - AIM: To evaluate a new supervision model for nursing students' placements in
      primary care in Sweden and to document students' opinions on their learning
      experiences in this setting. METHOD: Nursing students' (n=238) opinions were
      collected using a questionnaire administered before and after implementation of a
      new supervision model for student placements in primary care. RESULTS:
      Respondents were generally satisfied with their placements and rated factors that
      supported the new model: distinct structure for following students during the
      placement period; continuous caring experiences with some patients; having more
      than one district nurse as a mentor during the period; and seminars in primary
      care settings. However, just one third of respondents felt that they gained
      insight into how nursing research could be used in patient care. CONCLUSION: The
      evaluation of the new supervision model and learning opportunities in primary
      care were positively rated by respondents. Application of nursing research and
      planned time for reflection were ranked low, findings that are noteworthy and
      should be investigated further.

PMID- 19110854
TI  - Infection prevention and control in general practice.
AB  - Reducing healthcare-associated infections is a priority for the NHS. This article
      highlights infection prevention and control expectations for nurses working in
      general practice. Careful attention to detail and following recommended
      guidelines are good professional practice - protecting patients from infection
      and the practice from potential litigation.

PMID- 19110855
TI  - Management and prevention of norovirus outbreaks in hospitals.
AB  - Noroviruses are highly contagious and have become the most common cause of
      infectious gastrointestinal disease in industrialised countries. This article
      explores the epidemiology of norovirus and discusses strategies for prevention
      and control in hospitals. The need for new, updated evidence-based guidelines is
      highlighted.

PMID- 19110856
TI  - Patient dignity.

PMID- 19110857
TI  - In students' shoes.

PMID- 19110858
TI  - Seeing the ability.

PMID- 19110860
TI  - [Shock waves].

PMID- 19110859
TI  - Brain measurements.

PMID- 19110861
TI  - [Measures that favor the good treatment of dependent aged persons].

PMID- 19110862
TI  - [24th International Congress of the French Society of Psychogeriatrics: an
      interdisciplinary approach to work for and care of the aged ].

PMID- 19110863
TI  - [Applications and limits of the Bill of Rights and liberties of aged dependent
      people].

PMID- 19110865
TI  - [Care in geriatrics].

PMID- 19110864
TI  - [Geriatric evaluation].

PMID- 19110866
TI  - [Gerontologic technologies and life projects].

PMID- 19110867
TI  - [State of technical aids and gerontologic technologies].

PMID- 19110868
TI  - [Informing and evaluation the needs].

PMID- 19110869
TI  - [Ethics and gerontologic technologies].

PMID- 19110870
TI  - [Technology and Alzheimer disease].

PMID- 19110871
TI  - [New technologies and cognitive stimulation].

PMID- 19110872
TI  - [Formulating transmitting information to aged persons].

PMID- 19110873
TI  - [New gerontologic techniques in diagnosing falls].

PMID- 19110874
TI  - [What is the function of technologies concerning re-education and re
      adaptation?].

PMID- 19110875
TI  - [Gerontologic technologies in the service of home care].

PMID- 19110876
TI  - [6/12--The social service assistant].

PMID- 19110877
TI  - [Nurses, practice and families. 3/8--Access to records of aged persons].

PMID- 19110878
TI  - [6/6-Oral hygiene and deglutition disorders].

PMID- 19110879
TI  - Everywhere a conflict.

PMID- 19110880
TI  - Adolescent sleep, school start times, and teen motor vehicle crashes.
AB  - STUDY OBJECTIVES: To assess the effects of delayed high-school start times on
      sleep and motor vehicle crashes. METHODS: The sleep habits and motor vehicle
      crash rates of adolescents from a single, large, county-wide, school district
      were assessed by questionnaire before and after a 1-hour delay in school start
      times. RESULTS: Average hours of nightly sleep increased and catch-up sleep on
      weekends decreased. Average crash rates for teen drivers in the study county in
      the 2 years after the change in school start time dropped 16.5%, compared with
      the 2 years prior to the change, whereas teen crash rates for the rest of the
      state increased 7.8% over the same time period. CONCLUSIONS: Later school start
      times may both increase the sleep of adolescents and decrease their risk of motor
      vehicle crashes.

PMID- 19110881
TI  - Driving drowsy.

PMID- 19110882
TI  - CPAP therapy of obstructive sleep apnea in type 2 diabetics improves glycemic
      control during sleep.
AB  - BACKGROUND: Type 2 diabetes and obstructive sleep apnea (OSA) are frequently
      comorbid conditions. OSA is associated with increased insulin resistance, but
      studies of continuous positive airway pressure (CPAP) have shown inconsistent
      effects on glycemic control. However, endpoints such as hemoglobin A1c and
      insulin sensitivity might not reflect short-term changes in glycemic control
      during sleep. METHODS: We used a continuous glucose-monitoring system to measure
      interstitial glucose every 5 minutes during polysomnography in 20 patients with
      type 2 diabetes and newly diagnosed OSA. The measurements were repeated after an
      average of 41 days of CPAP (range 26-96 days). All patients were on a stable diet
      and medications. Each 30-second epoch of the polysomnogram was matched with a
      continuous glucose-monitoring system reading, and the sleeping glucose level was
      calculated as the average for all epochs scored as sleeping. RESULTS: The mean
      sleeping glucose decreased from untreated (122.0 +/- 61.7 mg/dL) to treated
      (102.9 +/- 39.4 mg/dL; p = 0.03 by Wilcoxon paired rank test). The sleeping
      glucose was more stable after treatment, with the median SD decreasing from 20.0
      to 13.0 mg/dL (p = 0.005) and the mean difference between maximum and minimum
      values decreasing from 88 to 57 mg/dL (p= 0.003). The change in the mean
      hemoglobin A1c from 7.1% to 7.2% was not significant. CONCLUSIONS: Our study is
      limited by the lack of a control group, but the results suggest that sleeping
      glucose levels decrease and are more stable after patients with type 2 diabetes
      and OSA are treated with CPAP.

PMID- 19110883
TI  - Clinical patterns of obstructive sleep apnea and its comorbid conditions: a data
      mining approach.
AB  - OBJECTIVES: Obstructive sleep apnea often results in a wide range of comorbid
      conditions. Although some conditions have been clearly identified as comorbid, a
      full clinical pattern of associated diseases has not been systematically
      documented. This research aimed to reveal the full pattern of comorbid conditions
      associated with OSA by employing a data mining technique. METHODS: A large data
      repository (the New South Wales inpatient Data Collection) collected between 1999
      and 2004 was mined, and all clinical diagnoses were coded with ICD-10-AM codes.
      RESULTS: A total of 60,197 cases (4% of total records) were identified as related
      to OSA (72.2% males, 27.8% females). OSA occurrence showed 2 peaks at 0-4 years
      and 55-59 years. A strikingly low occurrence was observed for the adolescent
      years. Conditions comorbid with OSA in adults by descending frequency were
      essential hypertension, obesity, hypercholesterolemia, type 2 diabetes, past or
      current tobacco use, and ischemic heart conditions. Obesity and OSA showed a
      similar time course of onset, with a latent period of 5 years for hypertension
      and type 2 diabetes and 15 years for chronic ischemic heart conditions. Comorbid
      conditions were predominantly of the cardiovascular, endocrine/metabolic and
      respiratory systems. The data also indicated OSA patients are high users of
      health services. CONCLUSIONS: The data mining technique confirms the prevalence
      of the disease, describes the age distribution patterns and time courses of
      disease development from obesity and OSAto comorbid conditions, and implicates
      possible interrelationships among these conditions and high cost of treating OSA
      patients.

PMID- 19110884
TI  - Relationship between snoring sound intensity and sleepiness in patients with
      obstructive sleep apnea.
AB  - STUDY OBJECTIVES: Subjectively assessed snoring and sleepiness are known to be
      related. However, no evidence supporting the usefulness of snoring measurements
      exists. We examined whether the objectively measured snoring intensity was
      correlated with sleepiness. METHODS: The records of 515 patients who underwent
      polysomnography for suspected obstructive sleep apnea were retrospectively
      reviewed. Subjective sleepiness was assessed using the Epworth sleepiness scale
      (ESS). Snoring intensity was assessed using the highest one percentile ambient
      sound pressure level (L1) attained while asleep during polysomnography. RESULTS:
      L1 was correlated with ESS in apneic patients with an apnea-hypopnea index (AHI)
      > or =15 (r = 0.38, p <0.0001), but not in other patients. The correlation in the
      apneic patients was preserved after adjustments for various confounding factors,
      including the AHI. A step-wise multiple regression in the apneic patients adopted
      desaturation time, L1, daily sleep time, subjective snoring, and nasal
      obstruction symptoms as determinants for the ESS. L1 was correlated with the mean
      pulse rate during polysomnography but not with sleep fragmentation variables
      after adjustment for the AHI. CONCLUSIONS: The measured snoring intensity was
      independently related to sleepiness in apneics. Snoring intensity may explain
      part of sleepiness that cannot be fully explained by ordinary polysomnographic
      variables.

PMID- 19110885
TI  - Subjective daytime sleepiness and daytime function in patients on stable
      methadone maintenance treatment: possible mechanisms.
AB  - INTRODUCTION: Subjects using opioids on a chronic basis have been reported to
      have a high prevalence of abnormal sleep architecture and central sleep apnea
      (CSA). The severity of CSA is, in part, related to blood opioid concentration.
      The aim of this study was to investigate subjective daytime sleepiness and
      daytime function in patients who are on stable methadone maintenance treatment
      (MMT) and to assess the possible mechanisms involving abnormal sleep
      architecture, CSA severity, and blood methadone concentration. METHODS: Fifty
      patients on MMT and 20 normal control subjects matched for age and body mass
      index were tested using polysomnography, blood toxicology, Epworth Sleepiness
      Scale (ESS), Functional Outcome of Sleep Questionnaire (FOSQ), and Beck
      Depression Inventory (BDI). RESULTS: The patients receiving MMT had significantly
      worse daytime function, were depressed, and had increased daytime sleepiness when
      compared with the control subjects (FOSQ 15.47 +/- 3.19 vs 19.4 +/- 0.47, BDI
      14.64 +/- 10.58 vs 2.05 +/- 2.46, ESS 7.1 +/- 5 vs 2.05 +/- 1.76; all p values <
      0.001). Nevertheless, daytime sleepiness in the patients receiving MMT was, on
      average, within the normal range (ESS < or = 10). Multiple regression analysis
      demonstrated that the severity of CSA, blood methadone concentration, and
      abnormalities in sleep architecture were not significant in predicting the
      variance of ESS or FOSQ (all p values > 0.05) in these patients receiving MMT.
      The BDI was the best predictive variable for FOSQ, explaining 16% of the variance
      (p = 0.004). CONCLUSIONS: Patients on stable MMT have, in general, normal
      subjective daytime sleepiness but impaired daytime function that partially
      relates to depression. The changes in sleep architecture, presence of CSA, and
      blood methadone concentrations do not significantly affect subjective daytime
      sleepiness and daytime function in these patients.

PMID- 19110886
TI  - Relationships between the Pittsburgh Sleep Quality Index (PSQI), Epworth
      Sleepiness Scale (ESS), and clinical/polysomnographic measures in a community
      sample.
AB  - STUDY OBJECTIVES: 1) To characterize PSQI and ESS scores, and their relationship
      to each other, in an adult community sample; 2) To determine whether PSQI and ESS
      scores, in combination with each other, were associated with distinct
      demographic, clinical, and sleep characteristics. METHODS: The PSQI, ESS,
      clinical rating scales, sleep diaries, actigraphy, and home polysomnography were
      collected from 187 community-dwelling adults (mean age 59.5 years, 47.1% women,
      41.2% African Americans) as part of a study investigating novel cardiovascular
      risk factors. Correlations, cluster analysis, principal components analysis,
      MANOVA, ANOVA, and regressions were used to characterize the relationships
      between the PSQI, ESS, and other study variables RESULTS: Mean PSQI score was 6.3
      (3.4), and mean ESS score was 8.2 (3.9). PSQI and ESS correlated weakly with each
      other (r = 0.16, p = 0.03), but segregated from each other on principal
      components analysis. Groups of participants categorized by either cluster
      analysis of PSQI and ESS scores, or by scores above or below traditional cut-off
      values, differed from each other on psychological/stress symptoms and
      quantitative and qualitative sleep diary measures, but not on actigraphic or
      polysomnographic measures. Specifically, higher PSQI scores were associated with
      female sex, greater psychological distress, and greater sleep disturbance on
      sleep diaries. CONCLUSIONS: The PSQI and ESS measure orthogonal dimensions of
      sleep-wake symptoms, but neither is related to objective sleep measures. The PSQI
      is more closely related to psychological symptom ratings and sleep diary measures
      than the ESS. These instruments are not likely to be useful as screening measures
      for polysomnographic sleep abnormalities.

PMID- 19110887
TI  - Health-related quality of life among drug-naive patients with narcolepsy with
      cataplexy, narcolepsy without cataplexy, and idiopathic hypersomnia without long
      sleep time.
AB  - OBJECTIVE: To evaluate the health-related quality life (HRQOL) of drug-naive
      patients with narcolepsy with cataplexy (NAwith CA), narcolepsy without cataplexy
      (NA without CA) and idiopathic hypersomnia without long sleep time (IHS without
      LST), and to explore the factors influencing the HRQOL. Factors associated with
      the occurrence of automobile accidents are also discussed. METHODS: A total of
      137 consecutive drug naive patients who met the criteria of the 2nd edition of
      the International Classification of Sleep Disorders (NA with CA, n = 28; NA
      without CA, n = 27; IHS without LST, n = 82) were enrolled. The patients were
      asked to fill out questionnaires, including the SF-36, Epworth Sleepiness Scale
      (ESS), sociodemographic variables, and items regarding driving habits and the
      experiences related to automobile accidents. RESULTS: All 3 diagnostic groups had
      significantly lower scores in most SF-36 domains compared with Japanese normative
      data. Significant differences among the 3 diagnostic groups were not observed.
      Specific factors in SF-36 domains were not found with multiple linear regression
      analyses, while disease duration was positively correlated with mental health
      among all subjects. Among the patients reporting driving habits, ESS score (> or
      =16) was positively associated with the experience of automobile accidents.
      CONCLUSIONS: Our results indicated that HRQOL decreases in drug-naive patients
      with hypersomnia, but neither disease category nor severity of the disorder
      appears as an associated factor. Increased severity of hypersomnia, however, was
      thought to play an important role in the occurrence of automobile accidents.

PMID- 19110889
TI  - A neurological cause of recurrent choking during sleep.
AB  - We describe a case of nocturnal choking episodes caused by insular seizures.
      Recurrent choking spells from sleep showed no response to treatment for sleep
      apnea or gastroesophageal reflux. Laryngoscopy revealed no abnormalities.
      Although continuous EEG monitoring during events was normal, ictal SPECT imaging
      showed increased radiotracer uptake in the left insular region, an area involved
      in sensation of the upper gastrointestinal tract. The episodes remitted after
      initiation of an antiepileptic drug. Obstructive sleep apnea is the most common
      cause for presentation to a sleep center, but seizures should remain in the
      differential diagnosis of nocturnal choking episodes.

PMID- 19110888
TI  - Prevalence of sleep related symptoms in four Latin American cities.
AB  - STUDY OBJECTIVES: to estimate the prevalence of the most common sleep related
      symptoms (SRS) in the metropolitan areas of Mexico City, Montevideo (Uruguay),
      Santiago (Chile), and Caracas (Venezuela). METHODS: The study consisted of a
      multistage cluster sampling of adults aged > or = 40 years living in metropolitan
      areas. All participants completed a questionnaire on sleep related symptoms.
      Simplified respiratory polygraphy during sleep was conducted on 188 subjects from
      Mexico City. Obstructive sleep apnea syndrome was defined as Epworth Sleepiness
      Scale score > or = 11 and respiratory disturbance index (RDI) > or = 15 events/h;
      a cut-off of 15 was chosen because of its high sensitivity and specificity in
      association with the portable monitor used in the study. RESULTS: The study
      included 4,533 subjects (1,062 in Mexico City, 941 in Montevideo, 1,173 in
      Santiago, and 1,357 in Caracas). Snoring was reported by 60.2% (95% CI 58.8% to
      61.6%), excessive daytime sleepiness by 16.4% (15.3% to 17.5%), observed apneas
      by 12.3% (11.4% to 13.3%), insomnia by 34.7% (33.3% to 36%), sedative use by
      15.1% (14.1% to 16.2%), daytime napping by 29.2% (27.7% to 30.6%), and a
      combination of snoring, sleepiness, and observed apneas by 3.4% (2.9% to 4%). Men
      had a higher frequency of snoring and daytime napping, whereas women reported
      more insomnia and sedative use. Prevalence of OSAS varied from 2.9% among
      subjects who denied snoring, excessive daytime sleepiness, and observed apneas,
      to 23.5% among those reporting these 3 symptoms. CONCLUSIONS: A high prevalence
      of sleep related symptoms and undiagnosed obstructive sleep apnea in Latin
      America was observed.

PMID- 19110890
TI  - Visual hallucinations and pontine demyelination in a child: possible REM
      dissociation?
AB  - An 11 year-old-boy acutely developed complex visual and acoustic hallucinations.
      Hallucinations, consisting of visions of a threatening, evil character of the
      Harry Potter saga, persisted for 3 days. Neurological and psychiatric
      examinations were normal. Ictal EEG was negative. MRI documented 3 small areas of
      hyperintense signal in the brainstem, along the paramedian and lateral portions
      of pontine tegmentum, one of which showed post-contrast enhancement. These
      lesions were likely of inflammatory origin, and treatment with immunoglobulins
      was started. Polysomnography was normal, multiple sleep latency test showed a
      mean sleep latency of 8 minutes, with one sleep-onset REM period. The pontine
      tegmentum is responsible for REM sleep regulation, and contains definite "REM-on"
      and "REM-off" regions. The anatomical distribution of the lesions permits us to
      hypothesize that hallucinations in this boy were consequent to a transient
      impairment of REM sleep inhibitory mechanisms, with the appearance of dream-like
      hallucinations during wake.

PMID- 19110891
TI  - Review of the possible relationship and hypothetical links between attention
      deficit hyperactivity disorder (ADHD) and the simple sleep related movement
      disorders, parasomnias, hypersomnias, and circadian rhythm disorders.
AB  - Recent evidence has been accumulating that the sleep of individuals with
      attention deficit hyperactivity disorder (ADHD) is not only disrupted in a
      nonspecific way but that ADHD has an increased association with simple sleep
      related movement disorders such as restless legs syndrome/periodic limb movements
      in sleep (RLS/PLMS), rhythmic movement disorder (body rocking and head banging),
      and parasomnias, such as disorders of partial arousal (sleep walking, sleep
      terrors, and confusional arousals). In addition increased associations have been
      reported between ADHD and hypersomnias such as narcolepsy and sleep apnea as well
      as circadian rhythm disorders, such as delayed sleep phase syndrome. These
      relationships are reviewed and the implications for such associations are
      explored. Patients with sleep disorders should be queried about the symptoms of
      ADHD and vice versa.

PMID- 19110892
TI  - Conception, pregnancy, delivery, and breastfeeding in a narcoleptic patient with
      cataplexy.

PMID- 19110893
TI  - Distressing nocturia.

PMID- 19110894
TI  - Concerns regarding the pediatric component of the AASM clinical guidelines for
      the manual titration of positive airway pressure in patients with obstructive
      sleep apnea.

PMID- 19110895
TI  - In reference to Positive Airway Pressure Titration Task Force of the American
      Academy of Sleep Medicine. Clinical guidelines for the manual titration of
      positive airway pressure in patients with obstructive sleep apnea. Journal of
      Clinical Sleep Medicine 2008;4:157-171.

PMID- 19110896
TI  - When to promote, and when to avoid, a population perspective.
AB  - Demography's population perspective, and the sampling methods that help produce
      it, are powerful but underutilized research tools. The first half of this article
      makes the case for more vigorous promotion of a population perspective throughout
      the sciences. It briefly reviews the basic elements of population sampling and
      then provides examples from both developed and developing countries of how
      population sampling can enrich random-assignment policy experiments, multisite
      studies, and qualitative research. At the same time, an ill-considered
      application of a population perspective to the problem of causal inference can
      hinder social and behavioral science. The second half of the article describes
      the "slippery slope" by which some demographic studies slide from providing a
      highly useful description about the population to using regressions to estimate
      causal models for that population. It then suggests that causal modeling is
      sometimes well served by a highly selective look at small subsets of a population
      with interesting variability in independent variables of interest. A robust
      understanding of causal effects, however, rests on convergence between selective
      and population-wide perspectives.

PMID- 19110897
TI  - A decomposition method based on a model of continuous change.
AB  - A demographic measure is often expressed as a deterministic or stochastic
      function of multiple variables (covariates), and a general problem (the
      decomposition problem) is to assess contributions of individual covariates to a
      difference in the demographic measure (dependent variable) between two
      populations. We propose a method of decomposition analysis based on an assumption
      that covariates change continuously along an actual or hypothetical dimension.
      This assumption leads to a general model that logically justifies the additivity
      of covariate effects and the elimination of interaction terms, even if the
      dependent variable itself is a nonadditive function. A comparison with earlier
      methods illustrates other practical advantages of the method: in addition to an
      absence of residuals or interaction terms, the method can easily handle a large
      number of covariates and does not require a logically meaningful ordering of
      covariates. Two empirical examples show that the method can be applied flexibly
      to a wide variety of decomposition problems. This study also suggests that when
      data are available at multiple time points over a long interval, it is more
      accurate to compute an aggregated decomposition based on multiple subintervals
      than to compute a single decomposition for the entire study period.

PMID- 19110898
TI  - Urbanization and fertility: an event-history analysis of coastal Ghana.
AB  - In this article, we undertake an event-history analysis of fertility in Ghana. We
      exploit detailed life history calendar data to conduct a more refined and
      definitive analysis of the relationship among personal traits, urban residence,
      and fertility. Although urbanization is generally associated with lower fertility
      in developing countries, inferences in most studies have been hampered by a lack
      of information about the timing of residence in relationship to childbearing. We
      find that the effect of urbanization itself is strong, evident, and complex, and
      persists after we control for the effects of age, cohort, union status, and
      education. Our discrete-time event-history analysis shows that urban women
      exhibit fertility rates that are, on average, 11% lower than those of rural
      women, but the effects vary by parity. Differences in urban population traits
      would augment the effects of urban adaptation itself Extensions of the analysis
      point to the operation of a selection effect in rural-to-urban mobility but
      provide limited evidence for disruption effects. The possibility of further
      selection of urbanward migrants on unmeasured traits remains. The analysis also
      demonstrates the utility of an annual life history calendar for collecting such
      data in the field.

PMID- 19110899
TI  - Fertility effects of abortion and birth control pill access for minors.
AB  - This article empirically assesses whether age-restricted access to abortion and
      the birth control pill influence minors' fertility in the United States. There is
      not a strong consensus in previous literature regarding the relationship between
      laws restricting minors' access to abortion and minors' birth rates. This is the
      first study to recognize that state laws in place prior to the 1973 Roe v. Wade
      decision enabled minors to legally consent to surgical treatment-including
      abortion-in some states but not in others, and to construct abortion access
      variables reflecting this. In this article, age-specific policy variables measure
      either a minor's legal ability to obtain an abortion or to obtain the birth
      control pill without parental involvement. I find fairly strong evidence that
      young women's birth rates dropped as a result of abortion access as well as
      evidence that birth control pill access led to a drop in birth rates among
      whites.

PMID- 19110900
TI  - Spousal mobility and earnings.
AB  - An important finding in the literature on migration has been that the earnings of
      married women typically decrease with a move, while the earnings of married men
      often increase with a move, suggesting that married women are more likely to act
      as the "trailing spouse." This article considers a related but largely unexplored
      question: what is the effect of having an occupation that is associated with
      frequent migration on the migration decisions of a household and on the earnings
      of the spouse? Further how do these effects differ between men and women? The
      Public Use Microdata Sample from the 2000 U.S. decennial census is used to
      calculate migration rates by occupation and education. The analysis estimates the
      effects of these occupational mobility measures on the migration of couples and
      the earnings of married individuals. I find that migration rates in both the
      husband's and wife's occupations affect the household migration decision, but
      mobility in the husband's occupation matters considerably more. For couples in
      which the husband has a college degree (regardless of the wife's educational
      level), a husband's mobility has a large, significant negative effect on his
      wife's earnings, whereas a wife's mobility has no effect on her husband's
      earnings. This negative effect does not exist for college-educated wives married
      to non-college-educated husbands.

PMID- 19110901
TI  - Wives and ex-wives: a new test for homogamy bias in the widowhood effect.
AB  - Increased mortality following the death of a spouse (the "widowhood effect") may
      be due to (1) causation, (2) bias from spousal similarity (homogamy), or (3) bias
      from shared environmental exposures. This article proposes new tests for bias in
      the widowhood effect by examining husbands, wives, and ex-wives in a longitudinal
      sample of over 1 million elderly Americans. If the death of an ex-wife has no
      causal effect on the mortality of her husband, then an observed association
      between the mortality of an ex-wife and her husband may indicate bias, while the
      absence of an effect of an ex-wife's death on her husband's mortality would
      discount the possibility of homogamy bias (and also of one type of shared
      exposure bias). Results from three empirical tests provide strong evidence for an
      effect of a current wife's death on her husband's mortality yet no statistically
      significant evidence for an effect of an ex-wife's death on her husband's
      mortality. These results strengthen the causal interpretation of the widowhood
      effect by suggesting that the widowhood effect is not due to homogamy bias to any
      substantial degree.

PMID- 19110902
TI  - No trend in the intergenerational transmission of divorce.
AB  - Previous studies on trends in the intergenerational transmission of divorce have
      produced mixed findings, with two studies (McLanahan and Bumpass 1988; Teachman
      2002) reporting no trend in divorce transmission and one study (Wolfinger 1999)
      finding that divorce transmission has weakened substantially. Using a stratified
      Cox proportional hazard model, we analyze data from the National Survey of
      Families and Households and find no evidence for any trend in divorce
      transmission. To reconcile apparent differences in results, we note that the
      General Social Survey data used by Wolfinger lack information on marital
      duration, permitting analysis only for whether respondents have divorced by
      interview. As a result, an apparent decline in divorce transmission could be due
      to inadequate adjustments for the longer exposures to risk by earlier marriage
      cohorts, yielding a higher probability of divorce by interview for earlier
      cohorts relative to more recent cohorts even if divorce risks are identical
      across all marriage cohorts. We confirm this possibility by using a series of
      discrete-time hazard logistic regressions to investigate the sensitivity of
      estimates of trends in divorce transmission to different adjustments for exposure
      to risk. We conclude that there has been no trend in the intergenerational
      transmission of divorce.

PMID- 19110903
TI  - Prenatal health investment decisions: does the child's sex matter?
AB  - Individuals invest in their own health, but children rely on parents to act on
      their behalf especially in the case of prenatal health. In this article, we ask,
      Do parents in the United States who choose to give birth allocate resources
      differently in the prenatal health of their sons and daughters when the sex of
      the child is known in advance? We pay special attention to prenatal health
      behaviors, which can be viewed as investment decisions, of first-generation
      immigrant parents from India and China, two countries with demonstrated son
      preference. Ultrasound receipt proxies for knowing fetal gender, enabling us to
      separate child sex-related biological differences from investment differences in
      sons' and daughters' health. There is evidence consistent with sex-selective
      abortions among Indian and Chinese populations, but among parents who choose to
      carry the pregnancy to term, our findings do not suggest that knowledge of child
      sex drives prenatal health investments in the United States, neither in the
      population as a whole nor among Indian and Chinese immigrants.

PMID- 19110904
TI  - Gender, resources across the life course, and cognitive functioning in Egypt.
AB  - In this article, I evaluate the life-course determinants of cognitive functioning
      among 1,003 women and men aged 50 and older in Ismailia, Egypt. Three questions
      motivate this analysis: (1) Do older women have poorer cognitive functioning than
      do older men?; (2) Do cognitive resources accrued in childhood and adulthood have
      net positive associations with later-life cognitive functioning for women and
      men?; and (3) To what extent do differences in the amounts and effects of women's
      and men's cognitive resources account for gaps in their cognitive functioning?
      Compared with men, women have lower Modified-Mini Mental Status Exam (M-MMSE)
      scores for overall cognitive functioning. Cognitive resources in childhood and
      adulthood are jointly associated with the M-MMSE score. About 83% of the gender
      gap in mean M-MMSE scores is attributable to gaps in men's and women's attributes
      across the life course. Gender gaps in childhood cognitive resources-and
      especially schooling attainment-account for the largest share (18%) of the
      residual gender gap in cognitive functioning.

PMID- 19110905
TI  - The impact of public hospital closure on medical and residency education:
      implications and recommendations.
AB  - BACKGROUND: Challenges around safety-net hospital closure have impacted medical
      student and resident exposure to urban public healthcare sites that may influence
      their future practice choices. OBJECTIVE: To assess the impact of the closure of
      a public safety-net teaching hospital for the clinical medical education of
      Charles Drew University medical students and residents. METHOD: Retrospective
      cohort study of medical students' and residents' and clinical placement into
      safety-net experiences after the closure of the primary teaching hospital.
      RESULTS: The hospital closure impacted both medical student and residency
      training experiences. Only 71% (17/24) of medical student rotations and 13%
      (23/180) of residents were maintained at public safety-net clinical sittings. The
      closure of the public safety-net hospital resulted in the loss of 36% of
      residency training spots sponsored by historically black medical schools in the
      United States and an even larger negative impact on the number of physicians
      training in underserved urban areas of Los Angeles County. CONCLUSION: While the
      medical educational program changes undertaken in the wake of hospital closure
      have negatively affected the immediate clinical educational experiences of
      medical students and residents, it remains to be seen whether the training site
      location changes will alter their long-term preferences in specialty choice and
      practice location.

PMID- 19110906
TI  - Predicting medication use in an elderly hypertensive sample: revisiting the
      Established Populations for Epidemiologic Studies of the Elderly Study.
AB  - Though some research has begun to examine specific factors related to race that
      should be targeted in the design of interventions to improve medication
      adherence, there remains an underreporting of factors that contribute to the use
      of hypertensive medications by race. METHODS: This study examined medication use
      reported by a sample of elderly, controlled and uncontrolled hypertensive
      patients from the North Carolina Established Populations for the Epidemiologic
      Studies of the Elderly (NC EPESE) study. RESULTS: In the adjusted final
      multivariable models of medication use over time in both Caucasian and African
      American women, those with higher BMI were more likely to report taking their
      medication over time; satisfaction with their medical care was predictive among
      Caucasian women and receiving treatment from a minority physician was predictive
      among African-American women. CONCLUSION: Focusing on individual-level
      characteristics and the different issues that may underlie specific ethnic
      groups, healthcare provider characteristics in particular may help to develop
      more precisely targeted interventions to improve a full range of healthcare
      services that are often needed by elderly hypertensive patients.

PMID- 19110907
TI  - Individuals' use of care while uninsured: effects of time since episode inception
      and episode length.
AB  - Few studies have addressed how an individual's use of care may vary over the
      course of an episode of their being uninsured or across uninsured episodes of
      varying duration. This research models the probability that an uninsured
      individual has: a) any medical expenditures or charges, and b) any office-based
      visit during each month of an uninsured episode. We find that the ultimate length
      of an individual's episode of being uninsured bears relatively little on
      individuals' use of healthcare in any particular month. We also find that the
      probability of healthcare utilization rises during the first year of the episode,
      with more use in the second 6 months of the year compared to the first 6 months.

PMID- 19110908
TI  - Disparities in the patterns and determinants of HIV risk behaviors among
      adolescents entering substance abuse treatment programs.
AB  - BACKGROUND: Black youth are disproportionately affected by the HIV/AIDS epidemic.
      This study examined disparities in patterns and determinants of sexual risk
      behaviors among black and white adolescents in substance abuse treatment
      programs. METHODS: We used pooled clinical data collected from 4,565 sexually
      active 12-17-year-old black (29.7%) and white (70.3%) adolescents entering
      outpatient and residential substance abuse treatment programs nationally.
      Multivariate logistic regression analyses were used to examine racial differences
      in patterns of sexual risk behaviors and the associations of these behaviors with
      demographic, socioenvironmental and psychosocial risk factors, including
      substance use and abuse, symptoms of mental disorders and criminal behaviors.
      RESULTS: Blacks were significantly more likely than whites to have had sex with
      multiple partners, purchased or traded sex and used substances to enhance their
      sexual experiences, even after adjusting for demographic, socioenvironmental and
      psychosocial risk factors. Substance use and abuse, internalizing symptoms and
      drug-related crimes were significantly associated with engaging in > or =2 sexual
      risk behaviors in both groups. Disparities in determinants of HIV risk were also
      found. For instance, male gender, single-parent custody and history of criminal
      justice involvement were associated with having had sex with multiple partners
      among blacks but not among whites. Demographic, socioenvironmental and
      psychosocial risk factors accounted for up to 30% of the variance in sexual risk
      in both groups. CONCLUSIONS: Black adolescents with substance use problems are at
      greater risk for HIV infection than their white peers because of their higher
      rates of sexual risk behaviors. Differences in co-occurring psychosocial problems
      did not fully explain racial disparities in sexual risk behaviors. HIV prevention
      programs for black adolescents in treatment should consider both individual and
      broader contextual factors that co-occur with sexual risk behaviors.

PMID- 19110909
TI  - Sociodemographic factors predict early discontinuation of HIV non-nucleoside
      reverse transcriptase inhibitors and protease inhibitors.
AB  - BACKGROUND/OBJECTIVE: HIV infection has a devastating impact on individual and
      public health, and affects populations disproportionately. Treatment with
      antiretroviral therapy (ART) saves lives, but long-term adherence to ART is
      critical to its success. We performed an observational cohort study to determine
      the influence of race, sex and other sociodemographic factors on early ART
      discontinuations among HIV-infected persons. METHODS: TennCare-enrolled adults of
      black or white non-Hispanic race beginning ART with either a non-nucleoside
      reverse transcriptase inhibitor (NNRTI) or protease inhibitor (PI) between 1996
      2003 (N=3654) were assessed for early discontinuation. A subgroup of
      discontinuations was validated using the primary medical record. RESULTS: Blacks
      were more likely than whites to discontinue NNRTIs (37 vs. 28%; P=0.003) and PIs
      (36 vs. 25%; P < or = 0.001). In multivariable models adjusting for race, sex,
      age, early HIV-related medical encounter, urban residence and TennCare enrollment
      category, black race, female sex and younger age were independent predictors of
      discontinuation among those starting PIs. Among persons starting NNRTIs, black
      race, younger age and a disability-based enrollment category predicted early drug
      discontinuation, but female sex did not. CONCLUSIONS: Our results suggest that
      sociodemographic factors were associated with early NNRTI and PI discontinuation
      in this population, and some factors were ART class specific.

PMID- 19110910
TI  - Peripheral blood gene expression profile associated with sustained virologic
      response after peginterferon plus ribavirin therapy for chronic hepatitis-C
      genotype 1.
AB  - We investigated the relationship between global gene expression in peripheral
      blood mononuclear cells (PBMCs) during the first 4 weeks of peginterferon alfa
      and ribavirin therapy and long-term eradication of hepatitis-C genotype 1
      infections in 23 patients. A sustained virologic response (SVR), defined as an
      undetected serum HCV ribonucleic acid (RNA) at week 72, was the virologic
      response endpoint. PBMC RNA was prepared at week 0 and week 4 from 23 patients
      (17 black and 6 white Americans), and hybridized to Affymetrix GeneChip HG-U133
      plus 2.0 arrays. Compared to week 0, 269 genes were differentially expressed at
      week 4 of treatment, including many genes regulated by alpha interferons and
      associated with host immunity (p<0.0001), cell signal transduction (p<0.001) and
      cellular protein metabolism (p<0.001). Expression of these 269 genes at week 0
      and week 4 did not differ significantly between patients with and without a SVR.
      In contrast, SVR was associated with differential expression of 98 genes at week
      4 (false discovery rate <0.01). Many of the genes have been implicated in control
      of HCV lifecycle and thus may play important roles in HCV clearance during
      peginterferon and ribavirin therapy.

PMID- 19110911
TI  - The importance of patient participation in second-line chemotherapy decisions:
      perspectives of African-American patients.
AB  - BACKGROUND: Minority populations have been considered to be less-active
      participants in their health and, consequently, more vulnerable to having
      decisions made for them. PROCEDURES: We interviewed African-American patients
      (N=26) with cancer who had recently consented to second-line chemotherapy,
      offered when their disease was no longer responding to standard first-line
      regimen. RESULTS: The majority (73%) reported involvement in the decision to
      start second-line chemotherapy. Forty-two percent reported making the decision
      together with their doctor. Support for autonomy was positively associated with
      education (p=0.01). Information seeking was considered more important than
      participating in decision-making. Patients who were less educated and had lower
      income reported stronger internal belief that their own actions and behaviors
      would determine their future health (p=0.04, p=0.007, respectively). Depression
      was identified in 35% of the study group and found not to be associated with any
      of the main outcomes. CONCLUSIONS: Although the majority of patients report
      participating in the decision to begin second-line chemotherapy, there are a
      diversity of views towards autonomy, the importance of information seeking and
      determinants of future health. Understanding patients' beliefs and attitudes
      around the time of disease recurrence may assist clinicians in supporting
      patients during this stressful time.

PMID- 19110912
TI  - Trends in the incidence of colorectal cancer in relation to county-level poverty
      among blacks and whites.
AB  - OBJECTIVE: The overall incidence of colorectal cancer has been decreasing rapidly
      in the United States since 1998. The extent to which the recent accelerated
      decline varies by socioeconomic status has not been examined. We analyzed trends
      in colorectal cancer incidence rates from 1992-2004 by area socioeconomic status,
      race, gender and stage at diagnosis. METHODS: Incidence data from 13
      Surveillance, Epidemiology and End Results reporting areas were used to examine
      temporal trends in age-standardized colorectal cancer incidence rates from 1992
      2004 by race, gender, stage at diagnosis and 3 levels of county poverty (counties
      with <10%, 10% to <20% and > or =20% of residents living below the poverty
      level). RESULTS: Among whites, colorectal cancer incidence rates decreased in
      both men and women residing in low- and moderate-poverty areas. The decrease
      involved both early- and late-stage disease in men and late-stage disease in
      women. In contrast, among those residing in high-poverty areas incidence rates
      increased for early-stage disease in men; rates were stable for late-stage
      disease in men and for both categories of stage in women. Among blacks, incidence
      rates decreased only in men residing in low-poverty areas. CONCLUSIONS: The
      recent decrease in colorectal cancer incidence has not yet benefited persons
      residing in high-poverty areas. Additional effort is needed to extend prevention
      and early detection measures to all segments of the population.

PMID- 19110913
TI  - Immunity to measles in pregnant mothers and in cord blood of their infants:
      impact of HIV status and mother's place of birth.
AB  - Antibody levels to measles were evaluated in 16 HIV-seropositive and 34
      seronegative pregnant women and in cord blood samples of their infants. Infants
      were followed prospectively, and a second blood sample was taken at 3-7 months of
      age. Antibody levels were significantly lower in HIV-seropositive pregnant women
      and HIV-exposed cord bloods at birth (p=0.01 and 0.04, respectively) compared to
      controls. The prevalence of protective immunity (> or =1.09 optical density
      ratio) was also significantly lower (p=0.02) in HIV-seropositive pregnant women.
      T-cell counts were lower in HIV-seropositive women who were nonimmune (268/mm3)
      to measles compared to those who were immune (618/mm3), but the difference did
      not reach significance (p=0.07). Immunity to measles declined significantly to
      nonprotective levels in all infant samples obtained at 3-7 months of age. A
      secondary analysis determined the impact of mother's place of birth. Antibody
      levels were significantly higher (p=0.03) in foreign-born HIV-seronegative
      pregnant women and cord blood samples (p=0.01) compared to U.S.-born HIV
      seronegative pregnant women seen in our inner-city clinic. Thus, HIV-seropositive
      and even some seronegative U.S.-born women may need a booster vaccine to ensure
      passage of adequate levels of passive immunity.

PMID- 19110914
TI  - Secular trends in excess fetal and infant mortality using perinatal periods of
      risk analysis.
AB  - Perinatal periods of risk (PPOR) provide an alternative analytical approach to
      studying infant mortality. Results can be used to focus community activities to
      improve infant and maternal health. This article demonstrates the use of PPOR to
      monitor trends in excess fetal and infant mortality related to disparities
      associated with race and ethnicity in Kansas City, MO (KC). Based on a comparison
      of PPOR analyses for 1996-2000 and 2001-2005, there was a 30% reduction in excess
      fetal and infant mortality in Kansas City and reductions for both non-Hispanic
      blacks (17%) and non-Hispanic whites (66.7%). However, the disparity ratio for
      excess mortality rates between non-Hispanic blacks and non-Hispanic whites nearly
      doubled. Prematurity, the most frequent cause of infant mortality in Kansas City
      during 2001-2005 accounted for 42.5% of the infant deaths. Being a teenage
      mother; having less than a high-school education; being unmarried; having an
      unintended pregnancy; being obese preconceptually; being diabetic; using
      substances such as tobacco or drugs during pregnancy; receiving late, inadequate
      or intermediate amounts of prenatal care; having a multifetal pregnancy; having a
      primary elective cesarean section; delivering a preterm infant or having a male
      infant; and being enrolled in Medicaid all increased the risk of infant death.

PMID- 19110915
TI  - An exploratory study of advance care planning in seriously ill African-American
      elders.
AB  - INTRODUCTION: The process of advance care planning (ACP) is often difficult to
      initiate and complete in minority populations, and African Americans are less
      likely to participate in ACP than non-Hispanic whites. We explored the
      perceptions of ACP among seriously ill African-American older adults. METHOD:
      Qualitative semistructured interviews and editing analysis of 10 community
      dwelling African-American elders in North Carolina. RESULTS: Three major themes
      were identified. First, participants had little to no familiarity with ACP; none
      reported that they participated in any substantive discussions regarding ACP.
      Inconsistent sources of healthcare information, in which there was little
      congruence in the information given and discordant of sources of information,
      were a second theme. Finally, participants denoted a deferred autonomy, in which
      they postponed involvement in future care decision-making but viewed themselves
      as active in their day-to-day living. CONCLUSION: Seriously ill African-American
      elders report both individual-level and health systems-level barriers to ACP.
      Efforts to improve ACP need to take into account the differences between the
      current, autonomy-based model of ACP within biomedicine and the values of
      minority older adults approaching the end of life.

PMID- 19110916
TI  - Depressive symptoms in a sample of women following perinatal loss.
AB  - OBJECTIVE: The aim of the study is to identify variables associated with
      depressive symptoms among women shortly after perinatal loss. METHOD: Respondents
      who agreed to participate in the study were interviewed, and sociodemographic
      data were obtained from them. The Hospital Anxiety and Depression Scale and the
      Edinburgh Postnatal Depression Scale (EDPS) were thereafter administered on each
      respondent. RESULTS: Respondents with perinatal loss had high rate of depressive
      symptoms (52% on EDPS), the rate was significantly higher, when compared with the
      control group (chi2 = 10.16, P=0.001). Factors significantly associated with
      depressive symptoms included previous perinatal losses, poor support from husband
      and occurrence of antenatal complications. CONCLUSION: Depressive reaction
      following perinatal loss is very common. Programs need to be designed to help
      these women cope with their loss and to reduce subsequent psychological
      morbidity.

PMID- 19110917
TI  - Challenges of utilizing immunostains to facilitate the diagnosis and management
      of metastatic adenocarcinoma.
AB  - Women presenting with metastases from an unknown primary site represent a growing
      diagnostic challenge. Treatment is based upon the results of several diagnostic
      radiographic modalities that may locate the occult primary and determine the
      extent of metastatic tumor burden. Immunostaining represents another modality
      that can be used to facilitate identification and management of occult primary
      carcinoma. In patients who present with advanced disease, combining standard
      techniques with immunostaining can usually aid in determining the most effective
      regimen for optimal palliation and, in some cases, prolonged survival. We
      describe metastatic adenocarcinoma of unknown primary presenting as a pericardial
      effusion and coincident supraclavicular adenopathy. The patient completed the
      chemotherapy and had stable metastatic tumor burden with an acceptable quality of
      life. Two years after initial diagnosis, the patient expired because of disease
      progression. Although immunohistochemical staining initially suggested metastatic
      breast carcinoma, her clinical course confirmed a lung primary.

PMID- 19110918
TI  - Early radiation-induced lung injury in a patient with prior diagnosis of
      bronchiolitis obliterans organizing pneumonitis.
AB  - This case study is to report the observation that clinically diagnosed radiation
      pneumonitis (geometrically conforming to the radiation treatment volume) occurred
      at a subthreshold radiation dose in a patient with a previous history of
      pathologically diagnosed bronchiolitis obliterans organizing pneumonitis.

PMID- 19110919
TI  - Comorbidities and challenges affecting African Americans with HIV infection.
AB  - The significant disparities in health outcomes that exist among racial minorities
      in the United States are clearly evident in the HIV epidemic. HIV
      disproportionately affects minorities, African Americans in particular. Current
      treatment of HIV/AIDS is complicated by medical problems such as hepatitis,
      diabetes and dyslipidemia, which also disproportionately affect African Americans
      and can significantly impact the complexity of clinical care. In addition,
      untreated psychological problems such as depression and societal barriers to
      adequate medical care may decrease treatment adherence and increase HIV-related
      morbidity and mortality among African Americans. Consideration of these issues by
      healthcare providers is necessary to optimize care and improve treatment outcomes
      for African Americans with HIV infection.

PMID- 19110920
TI  - Reduction of the infant mortality rate in the West Indies.

PMID- 19110921
TI  - Pulmonary edema associated with methylene blue dye administration during sentinel
      lymph node biopsy.
AB  - Sentinel lymph node biopsy (SLNB) is an established procedure for staging early
      breast cancer. Recently, methylene blue dye has been advocated as a safe,
      efficacious and cost-effective substitute for isosulfan blue in sentinel lymph
      node mapping. In this case report, we describe a 44-year-old woman who developed
      pulmonary edema associated with the use of methylene blue dye for SLNB.

PMID- 19110922
TI  - Diffuse alveolar hemorrhage as an initial presentation of systemic lupus
      erythematosus.
AB  - Diffuse alveolar hemorrhage is a rare but fatal complication in patients with
      systemic lupus erythematosus. It has rarely been reported to occur as the initial
      presentation in lupus patients. We report a 55-year-old female Jehovah's witness
      who presented with diffuse alveolar hemorrhage as the initial manifestation of
      systemic lupus erythematosus. She responded favorably to early intravenous pulse
      methylprednisolone and cyclophosphamide along with hemotherapy she accepted once
      over the course of her hospital stay. Initially, there was clinical improvement,
      but relapsing of her alveolar hemorrhage 15 days later. It is important to keep
      in mind that lupus patients can present initially with this lethal pulmonary
      complication. Early identification and initiation of therapy are crucial in order
      to affect survival of these patients.

PMID- 19110923
TI  - Coronary blood flow and flow reserve in aortic stenosis: effect of aortic valve
      therapy.

PMID- 19110924
TI  - Initial experience with the Impella Recover LP 2.5 micro-axial pump in patients
      undergoing high-risk coronary angioplasty.
AB  - INTRODUCTION: The Impella LP 2.5 device is a new percutaneous left ventricular
      assist device, an intravascular micro-axial blood pump designed for short term
      circulatory support in conditions characterized by profoundly reduced ventricular
      function. Percutaneous coronary intervention (PCI) is increasingly being used in
      patients who have severely compromised left ventricular contractility and complex
      coronary lesions, including multivessel disease. METHODS: Three patients (pts)
      underwent elective PCI with the use of the Impella system. All were very poor
      candidates for surgery because of severe comorbidities, with mean logistic
      EuroSCORE 39.3%. Echocardiography was used to rule out anatomical
      contraindications before implantation of the device. All pts had previous
      myocardial infarctions and impaired left ventricular (LV) function with LV
      ejection fraction <25-30%. We evaluated the effects of the pump on cardiac
      output, mean pulmonary wedge pressure and mean blood pressure, using right heart
      catheterization. We also assessed hemoglobin, cardiac enzymes (CK, CKMB and
      troponin), creatinine and NT-proBNP levels before and the day after the
      intervention. RESULTS: The procedure was uncomplicated, without any acute, device
      related adverse events during LV support. The Impella was used for a mean time of
      9.3 hours (range 2 to 24 hours) and was removed immediately after the
      intervention in all but one patient. The device did not induce or increase aortic
      valve regurgitation. Two pts needed pharmacologic inotropic support during the
      procedure. Mean blood pressure increased in all 3 pts without pulmonary wedge
      pressure reduction, presumably due to a combination of pump function and PCI
      induced ischemia. The mean drop in hemoglobin levels was 1.7 g/dl. The mean
      increase in creatinine levels due to contrast was 1 mg/dl. NT-proBNP showed a
      variable response. Two pts remained stable at follow up and one expired one month
      later due to worsening heart failure. CONCLUSIONS: The growing heart failure
      population and the benefit of revascularization in patients with severe LV
      dysfunction have led to an increase in the number of mechanically assisted
      percutaneous coronary interventions. Circulatory support with the Impella LP 2.5
      pump during high risk PCI is feasible, but larger studies are required to
      demonstrate its efficacy in these severely compromised and vulnerable patients.

PMID- 19110925
TI  - Cost-minimisation analysis of oral anticoagulant therapy monitoring methods: the
      case for prothrombin time self-monitoring.
AB  - INTRODUCTION: Anticoagulant therapy is usually chronic and is indicated for the
      treatment of several medical conditions. The most common of these include
      patients with mechanical heart valves and those suffering from atrial
      fibrillation. METHODS: This study compares two methods of oral anticoagulant
      therapy (OAT) monitoring: traditional prothrombin time measurement and self
      measuring or self-regulation by the patient. As numerous published studies
      indicate that the two methods are equally effective (while underlining
      significant deviations in the frequency of complications), a cost-minimisation
      analysis was applied. The methodology was based on the consensus of experts from
      different geographical regions and health service sets. All costs and benefits
      attributable to patient treatment were examined and analysed from the perspective
      of the Greek National Health System (NHS). RESULTS: From the analysis it was
      estimated that the savings from the use of self-monitoring could reach Euro
      6,132,750 at market prices for a five-year period. The potential economic benefit
      from the expansion of self-monitoring to all eligible patients was equal to
      approximately 10% of the total treatment cost of the entire patient population
      under OAT in Greece. In addition, the social benefits resulting from higher
      prevention rates of possible complications, as well as the improvement in
      patients' quality of life should not be underestimated. The total reduction in
      private expenditure deriving from the expansion of self-monitoring was estimated
      at Euro 3,096,000, while savings for the NHS were estimated at Euro 2,473,317
      over a five-year period. CONCLUSIONS: The benefit to the healthcare system from
      the use of self-monitoring is significant, and the further use of this technology
      could contribute to the rational allocation of healthcare resources.

PMID- 19110926
TI  - Transcatheter aortic valve implantation: first Greek experience.
AB  - INTRODUCTION: Percutaneous aortic valve replacement represents an alternative to
      conventional open-heart surgery for selected high-risk patients without the need
      for sternotomy, aortotomy, or cardiopulmonary bypass. We present the first Greek
      series of transcatheter prosthetic aortic valve implantation procedures,
      performed in our centre. METHODS: All 12 patients (age 81 +/- 5 years) had
      severe, symptomatic, calcific aortic stenosis and were judged not to have a
      reasonable surgical option by a medical team including experienced cardiac
      surgeons. The patients' mean logistic EuroSCORE was 34 +/- 15% (min 11%, max
      61%). Eight (8) of them underwent transfemoral (SAPIEN, Edwards 23 mm valve in 7
      and 26 mm in 1 patient) and 4 transapical (26 mm in 2 and 23 mm in 2 patients)
      prosthetic aortic valve implantation, all in the cardiac catheterisation
      laboratory under general anaesthesia. RESULTS: The procedural, in-hospital and 2
      month (mean follow up 50 days, min 17, max 122 days) mortality was 0%. The length
      of hospital stay was 8 +/- 2 days (min 5, max 12 days). The aortic valve area
      increased from 0.64 +/- 0.14 cm2 to 1.83 +/- 0.14 cm2 and the mean pressure
      gradient decreased from 57 +/- 23 mmHg to 10 +/- 3 mmHg post-implantation
      (p<0.001 for both). The patients' mean NYHA functional status improved from 2.8
      +/- 0.7 to 1.3 +/- 0.5 at follow-up (p<0.001). CONCLUSIONS: Our initial
      experience with transcatheter prosthetic aortic valve implantation demonstrates
      that it can be performed safely and with excellent short and mid-term clinical
      outcomes.

PMID- 19110927
TI  - Reduced pressure wave reflections in patients with active clinical status of
      Adamantiades-Behcet disease.
AB  - INTRODUCTION: Acute and chronic inflammation has a deleterious effect on arterial
      structure and function. Increased arterial stiffness and pressure wave
      reflections may provide a pathophysiological link between inflammation and
      increased cardiovascular risk. Adamantiades-Behcet disease (ABD), a relapsing
      inflammatory vasculitis, is associated with impaired arterial properties
      modulated by corticosteroids. The effect of inflammation on arterial properties
      during the active state of ABD is not well known. METHODS: In 47 subjects with
      ABD, under no corticosteroid treatment, we examined pressure wave reflections
      (augmentation index, AIx) and central pressures by pulse wave analysis, as well
      as local aortic stiffness and left ventricular function by high resolution
      ultrasound. Thirty subjects with similar cardiovascular risk factors served as a
      control group. RESULTS: Subjects with active ABD (n=11) had lower AIx and central
      systolic blood pressure (CSBP), but similar peripheral blood pressure, stroke
      volume, and slightly higher local aortic stiffness in comparison to patients with
      inactive ABD (n=36) (Alx: 12.6 +/- 11.4 vs. 23.2 +/- 19.1%, p=0.009; CSBP 104.2
      +/- 12.4 vs. 115.4 +/- 15.7 mmHg, p=0.028). The arrival of the reflected pressure
      wave within the cardiac cycle was significantly delayed in subjects with active
      ABD. Low values of AIx (<10.5%) predicted with 73% sensitivity the presence of
      active ABD. CONCLUSIONS: Patients with ABD, not treated with corticosteroids,
      have decreased pressure wave reflections and CSBP in the presence of active
      disease, possibly due to peripheral arterial vasodilation, but not due to altered
      left ventricular or aortic function. The underlying pathophysiological mechanisms
      and the role of low AIx in the presence of systemic inflammation need to be
      investigated further.

PMID- 19110928
TI  - Study of atheromatous plaque using intravascular ultrasound.

PMID- 19110929
TI  - Smoking cessation in cardiovascular patients.

PMID- 19110930
TI  - Percutaneous transluminal coronary angioplasty in a patient with three small
      vessel disease: the role of intravascular ultrasound.

PMID- 19110931
TI  - Edge-to-edge repair of tricuspid valve in a corrected transposition of the great
      vessels.
AB  - We describe the case of a 27-year-old Caucasian woman with corrected
      transposition of the great vessels, who presented with cardiac failure. She had
      severe regurgitation of the systemic tricuspid valve with a huge annulus that was
      not suitable for annuloplasty. She underwent a successful repair using the
      Alfieri edge-to-edge technique and was asymptomatic 15 months after surgery. Such
      a repair has not been reported in the past.

PMID- 19110932
TI  - Intracardiac echocardiography-facilitated ablation of a left-lateral bypass tract
      in a patient with atrial septal aneurysm.
AB  - Intracardiac echocardiography (ICE) has been used as an adjunctive tool during
      electrophysiological procedures, mainly to increase the safety of transseptal
      puncture. We present the case of a young patient with a left-lateral bypass tract
      and atrial septal aneurysm, in whom ICE delineated the underlying anatomy,
      excluded the presence of thrombus and facilitated access to the left atrium
      through a small atrial septal defect, avoiding the risk of needle puncture for
      interatrial septal crossing.

PMID- 19110934
TI  - Wide-QRS tachycardia inducible by both atrial and ventricular pacing.
AB  - We describe an interesting case of an atriofascicular re-entrant tachycardia due
      to a Mahaim pathway. The differential diagnosis is discussed and a review of the
      relevant literature is presented.

PMID- 19110933
TI  - Atrioventricular re-entrant and ventricular tachycardias of left origin: a rare
      combination.
AB  - The simultaneous occurrence of atrial and ventricular tachycardias, or junctional
      and ventricular tachycardias, has been reported previously. We report on a
      patient presenting with syncope and demonstrating, simultaneously,
      atrioventricular re-entrant tachycardia and ventricular tachycardia of left
      origin. A left lateral concealed pathway was responsible for the former
      arrhythmia, while the latter arrhythmia was located in the anterolateral wall of
      the left ventricle. This is a rare type of double tachycardia and stresses the
      need for a thorough investigation of patients who have concealed accessory
      pathways and a previous history of atrioventricular re-entrant tachycardia, when
      they present with syncope.

PMID- 19110935
TI  - Beta-thalassemia heart disease: is it time for its recognition as a distinct
      cardiomyopathy?

PMID- 19110936
TI  - Personalised health care: an emerging aim.

PMID- 19110937
TI  - Reviews of Environmental Contamination and Toxicology. Preface.

PMID- 19110938
TI  - Assessing the discharge of pharmaceuticals along the Dutch coast of the North
      Sea.
AB  - This chapter assessed the annual median discharge of over 100 pharmaceuticals to
      the DCZ. Calculations were based on pharmaceutical concentrations in surface-,
      sewage-, and industrial water in the Netherlands. In 2002, riverine discharge to
      the DCZ for individual pharmaceuticals varied from 0 (concentration below LOD) to
      27 t yr(-1). However, in 2002 the annual amount was less than 2 t for 75% of the
      studied pharmaceuticals. The highest loads were calculated for X-ray contrast
      media, that is, values of 18-27 t yr(-1) for iopromide. The top 20
      pharmaceuticals discharged by rivers to the DCZ are dominated by X-ray contrast
      media (n = 7), followed by antibiotics (n = 6), analgesics/antipyretics/anti
      inflammatory drugs (n = 2), beta blockers (n = 2), fibrates/lipid regulators (n =
      1), veterinary antibiotics (n = 1), and others (n = 1). The direct discharge
      (sewage water and industrial water) of pharmaceuticals to the DCZ, in 2002, for
      individual pharmaceuticals varied from < 0.0009 to 0.27 t yr(-1) for sewage
      water, and from < 0.0009 to 0.33 t yr(-1) for industrial wastewater. The highest
      loads were calculated for sotalol (beta blocker) and diatrizoic acid (X-ray
      contrast medium) in sewage water and industrial wastewater, respectively. The
      direct discharge of pharmaceuticals to the DCZ is < 5% of that from riverine
      discharge. The discharge of these pharmaceuticals to the DCZ in 2002 is in the
      same order of magnitude as the discharge rates of the mandatory OSPAR substances
      Cd (8.8-10 t yr(-1)) and Hg (3.3 t yr(-1)), and are higher than the discharge
      rates of the mandatory substance lindane (0.041-0.055 t yr(-1)) and the
      recommended substance PCBs (0.217 t yr(-1)). Although some pharmaceuticals are
      discharged in significant amounts to the DCZ, the human and ecotoxicological
      risks of these highly biologically active compounds are largely unknown. To
      determine the environmental hazard and risk of discharged pharmaceuticals to the
      marine environment, future research should focus on a baseline study and a risk
      assessment of the discharged pharmaceuticals in the DCZ.

PMID- 19110939
TI  - Methods for deriving pesticide aquatic life criteria.
AB  - Environmental regulators charged with protecting water quality must have
      scientifically defensible water quality goals. For protection of aquatic life,
      regulators need to know what levels of contaminants a water body can tolerate,
      without producing adverse effects. The USEPA has developed water quality criteria
      for many chemicals, but few are for current-use pesticides. Other countries also
      derive aquatic life criteria utilizing a variety of methodologies. As a prelude
      to developing a new criteria derivation methodology, this chapter explores the
      current state of aquatic life criteria derivation around the world. Rather than
      discussing each methodology independently, this review is organized according to
      critical elements that must be part of a scientifically defensible methodology.
      All of the reviewed methodologies rely on effects data to derive aquatic life
      criteria. Water quality criteria may be derived from single-species toxicity data
      by statistical extrapolation procedures (for adequate data sets), or by use of
      empirically based AFs (for data sets of any size). Assessment factor methods are
      conservative and have a low probability of underestimating risk, with a
      concomitant high probability of overestimating risk. Extrapolation methods may
      also under-, or overestimate risk, but uncertainty is quantifiable and is reduced
      when larger data sets are used. Although less common, methods are also available
      for criteria derivation using multispecies toxicity data. Environmental toxicity
      of chemicals is affected by several factors. Some of these factors can be
      addressed in criteria derivation, and some cannot. For example, factors such as
      magnitude, duration and frequency of exposure may be incorporated into criteria,
      either through use of time-to-event and population models or by derivation of
      both acute and chronic criteria that have duration and frequency components.
      Aquatic species may be exposed to hydrophobic organic chemicals by multiple
      routes. They may take up residues directly from water, or may be exposed
      dietarily, or combinations of both. Unfortunately, to properly address such
      multiple routes in criteria derivation, food web models are needed that work for
      chemicals that have specific modes of action. Similarly, both bioavailability and
      toxicity parameters may contribute to derivation of criteria, providing
      sufficient data are available. Ecotoxicological effects and physical-chemical
      data are needed for criteria derivation. The quality and quantity of required
      data are clearly stated in existing methodologies; some guidelines provide very
      specific data quality requirements. The level of detail provided by guidelines
      varies among methodologies. Most helpful are those that provide lists of
      acceptable data sources, descriptions of adequate data searches, schemes for
      rating ecotoxicity data, specifications of required data types (e.g., acute vs
      chronic), and instructions for data reduction. Many methodologies present
      procedures for deriving criteria from both large and small data sets. Very small
      data sets may be supplemented through the use of QSARs for selected pesticides,
      and through the use of models such as ICE (for prediction of toxicity to under
      tested species), and ACE (for estimation of chronic toxicity from acute data).
      The toxicity of mixtures is addressed by several existing methodologies. In some
      cases, additional AFs are applied to criteria to account for exposure to
      mixtures, whereas in others, concentration addition models are used to assess
      compliance. Multiple stressors and bioaccumulation are also addressed in some
      methodologies, by providing for application of additional safety factors. Methods
      are also available for translating dietary exposure limits for humans or other
      fish-eating animals into water concentrations. Options for addressing the safety
      of TES exist, and rely heavily on data from surrogate species to derive criteria.
      Utilizing partition coefficients, criteria may be harmonized across media to
      ensure that levels set to protect one compartment do not result in unacceptable
      levels in other compartments. Several methodologies derive criteria from entire
      data sets through the use of statistical extrapolations; other methods utilize
      only the lowest (most sensitive) data point or points. Utilization of entire data
      sets allows derivation of confidence limits for criteria, and encourages data
      generation. Criteria derivation methodologies have improved over the past two
      decades as they have incorporated more ecological risk assessment techniques. No
      single existing methodology is ideal, but elements of several may be combined,
      and when used with newer risk assessment tools, will produce more usable and
      flexible criteria derivation procedures that are protective.

PMID- 19110940
TI  - Platinum group elements in the environment: emissions and exposure.
AB  - PGEs (Pt, Pd, Ru, Ir, and Os) are a relatively new group of anthropogenic
      pollutants. Specific useful properties of these metals (high resistance to
      chemical corrosion over a wide range of temperatures, high melting point, high
      mechanical resistance, and high plasticity) have fomented rapid growth of new and
      existing applications in various economic and industrial sectors. These metals
      are not only used in the chemical, petrochemical, electrical, and electronics
      industries but also PGE use, in various industries, has dramatically increased
      emissions of these metals to the environment; emissions from vehicle catalytic
      converters and hospital wastewater discharges are particularly significant. The
      environmental benefits of using PGEs in vehicle catalytic converters are clear.
      These metals catalyze the conversion of toxic constituents of exhaust fumes (CO,
      HCs, NOxs) to water, CO2, and molecular nitrogen. As a result of adverse physico
      chemical and mechanical influences on the catalyst surface, PGEs are released
      from this layer and are emitted into the environment in exhaust fumes. Research
      results indicate that the levels of such emissions are rather low (ng km(-1)).
      However, recent data show that certain chemical forms of PGEs emitted from
      vehicles are, or may be, bioavailable. Hence, the potential for PGEs to
      bioaccumulate in different environmental compartments should be studied, and, if
      necessary, addressed. The use of Pt in anticancerous drug preparations also
      contributes to environmental burdens. Pt, when administered as a drug, is
      excreted in a patient's urine and, as a consequence, has been observed in
      hospital and communal wastewater discharges. Few studies have been published that
      address bioavailability, mode of penetration into live organisms, or
      environmental fate of PGEs. The toxic effect of these metals on living organisms,
      including humans, is still in dispute and incompletely elucidated. Contrary to
      some chlorine complexes of Pt, which most frequently cause allergic reactions,
      the metallic forms of PGEs are probably inert; however, they may undergo
      transformation to biologically available forms after release to the environment.
      Because exposure to PGEs may result in health hazards, it is necessary to
      evaluate the risks of human exposure to these metals. Available data show that
      the highest exposed groups (Leceniewska et al. 2001) are individuals who work in
      refineries, chemical plants, electronics plants, jewelry production, oncological
      wards (medical personnel), and road maintenance; also highly exposed are women
      who have silicone breast implants. The effects of PGE exposure in live organisms
      include the following: asthma, miscarriage, nausea, hair loss, skin diseases,
      and, in humans, other serious health problems. As production and use of PGEs
      grow, there is a commensurate need to generate additional experimental and
      modeling data on them; such data would be designed to provide a better
      understanding of the environmental disposition and influence on human health of
      the PGEs.

PMID- 19110941
TI  - [Carcinoma of the gallbladder--current surgical treatment options].
AB  - BACKGROUND: The effect of radical resection in gallbladder cancer is still area
      of debate. AIM OF STUDY: To determine the criteria of surgery in primary and
      incidental gallbladder cancer. method: Eighty-four patients with gallbladder
      cancer were evaluated between 1999 and 2008. Sixty patients (72.4%) were
      symptomatic. Explorative laparotomy was performed in 40 (66.7%), palliative
      procedure in 5 (8.3%) patients in stage pT3-4, N1, M0-1. Cholecystectomy only or
      completed with wedge resection of the gallbladder bed and lymfadenectomy as
      radical procedure was performed only in 7 (1.7%) patients in pT1-2, N0-1, M0.
      Twenty four (28.6%) patients had incidental gall bladder carcinoma. Radical
      cholecystectomy was performed in 4 (16.7%) - pT1a, N0, M0, palliative
      cholecystectomy in 3 patients (12.5%) - pT3, N1, M0. Radical reoperation was
      performed in 15 (62.5%) patients in stage pT1b-2, N0-1, M0. RESULTS: Patients
      survival after explorative laparotomy and palliative procedures was no longer
      than 7 months. Four from seven patients died after radical operation 12-18 months
      after operation. Six from 15 radically re-operated patients are alive in interval
      4 months and 8 years. Nine patients died in interval 9 months and 4 years after
      re-operation. CONCLUSION: Radical surgical procedure is the treatment of choice
      for patients with gall bladder carcinoma especially in stage pT1-2, N0, M0.

PMID- 19110942
TI  - [Multidisciplinary cooperation in the management of serious bleedings
      complicating necrotizing pancreatitis--a case review].
AB  - Acute necrotising pancreatitis is connected with a high complication rate. The
      most serious ones are hemorrhagic complications with bleeding from vascular
      structures erosions. Authors report a case of endovascular treatment of
      surgically untreatable lesion of portal vein. In this case stentgraft was
      successfully implanted to cover the erosion and stop the bleeding. Percutaneous
      transhepatic route was used.

PMID- 19110943
TI  - [Treatment strategy in non-parasitic benign cysts of the liver].
AB  - The authors present the problems of treatment of benign non-parasitic cystic
      liver diseases. Recent diagnostic and treatment strategy is demonstrated at the
      cohort of 25 patients (16 women and 9 men), who were operated on Department of
      Surgery, Medical School and Teaching Hospital Pilsen, Charles University Prague
      between years 2002-2007. The average age was 59.9 years (38-86 years). We
      performed 15 laparoscopic fenestrations, 5 opened fenestrations, three
      enucleations of cysts and one left lobectomy and one central liver resection. The
      resections were performed because of diagnostic uncertainty to verify
      histological character of leasions at patients after previous operation of
      gastrointestinal tract for malignancy. Histological diagnosis was proved in 16
      cases solitary liver cyst, in 7 cases of polycystic liver disease, one biliary
      cystadenoma and one retentive cyst. The reoperation of symptomatic solitary liver
      cyst was performed in one patient after 12 months from primary operation. The
      average follow-up of patients after surgical treatment was 41 months (5-96
      months). Solitary liver cysts are indication to laparoscopic fenestration with
      biopsy in case of evidence of symptoms. Polycystic liver diseases are treated
      conservative and surgical treatment is indicated at outstanding and apparent
      symptomatology of this disease, where is possible to demonstrate preoperatively
      one or more dominant cysts.

PMID- 19110944
TI  - [Acute scrotum is a condition requiring surgical intervention].
AB  - Acute scrotum (AS) is a clinical syndrome, in which authors indicate a surgical
      exploration of the scrotum. We retrospectively analyzed the group of 354 patients
      in 10 years (1997-2006) to compare the preoperative findings with the diagnosis
      of surgical exploration. The aim was to actualize diagnostics and therapeutic
      management. PATIENTS AND METHODS: We focused on the age of patients, incidence of
      nosological units of AS and preoperative and surgical diagnosis. RESULTS: 334
      boys were operated on from the whole group - 354 patients. Most frequent
      incidence of AS was in the age group 8-12 (55%). Torsion of testicular appendix
      or epididymis is the most frequent cause of AS in our group - 204, 59%. In this
      group of patients ultrasound confirmed the diagnosis only in 120 patients, 65%.
      Testicular torsion was managed in 74 boys (30 neonates), in 40 of them we
      decided, mostly at the second look operation after 48-72 hours, for testicle
      ablation caused by the organ avitality. In all patients with testicular torsion
      ultrasound confirmed the diagnosis, 100%. In 10 boys we found testicular tumor.
      In the group of 334 patients operated on, there were no serious complications.
      DISCUSSION: Testicular torsion and tumor are the units in which the surgical
      exploration is performed without discussion. Beside that, torsion of the
      testicular or epididymic appendix is the most frequent occurring diagnosis. There
      is a group of surgeons, who performed in this unit conservative management.
      CONCLUSIONS: after the analysis of the group of our patients we actualized the
      guidelines used in the management of AS in children. Urgent surgical exploration
      in boys with AS still seems to be the method of choice.

PMID- 19110945
TI  - [Outcomes of pancreatic resections in the elderly and geriatric patients].
AB  - As a result of the population aging, we are confronted with the problematics of
      geriatric patients more and more frequently. The aim of this retrospective study
      was to compare outcomes of pancreatic resections in patients of three different
      age groups. During 2000-2007, 150 pancreatic resections were performed in our
      clinic, including 34 (22.7%) patients aged 65 and over at the time of the
      procedure and 5 (3.3%) patients over 75 y.o.a. The procedures were heterogenous,
      including indications for oncologic diagnoses, as well as for chronic
      pancreatitis. Our assessment demonstrated no significant differences in the 30
      day postoperative mortality between the group of subjects over 65 y.o.a,
      geriatric group (i.e. over 75 y.o.a) and the group of subjects below 54 y.o.a.
      (8.8% vs. 0% vs. 5.2%). Furthermore, the postoperative morbidity showed no
      statistically significant differences between the all three groups (30.2% vs.
      29.4% vs. 20%). The commonest postoperative complications included secondary
      healing of the surgical wound (7.8%) and pancreatic fistules (6.9%) in the group
      of subjects below 65 y.o.a., and insufficiency of the pancreatic-jejunal
      anastomosis (5.8%) and hepatic- jejunal anastomosis (5.88%) in the group aged 65
      and over. Pancreatic-jejunal anastomosis insufficiency, complicated by
      consecutive bleeding, contributed to postoperative mortality most significantly.
      Significant increase in postoperative complication rates connected to proximal
      pancreatoduodenectomies and total pancreatoduodenectomies, was recorded in
      patients over 65, compared to those in the young patient group (p = 0.014). No
      statistically significant relation was found between a particular comorbidity and
      onset of postoperative complications or deaths in patients over 65 or geriatric
      patients. Based on the results, the authors do not consider the patient's age a
      contraindication for pancreatic resection procedures. Radical resections can be
      performed with acceptable mortality and morbidity rates in geriatric patients.

PMID- 19110946
TI  - [Use of allogenous material in the management of spina bifida aperta].
AB  - AIM: "Conditio sine qua non" in the management of open neural tube defects
      includes closure of all layers with as minimum as possible tension left within
      the suture region, in order to prevent early, as well as long-term postoperative
      complications. In extensive fascial defects, the authors used the Gore-Tex patch
      as an alternative to myofascial or fasciocutaneous flaps. PATIENTS AND METHODS:
      From January 2004 to January 2008, 23 patients suffering from open spina bifida
      underwent surgery in the Bratislava Pediatric Surgery Centre. In 17 subjects, the
      fascia was sutured following a myofascial release, in 2 subjects the suture was
      secured with tissue adhesive. In 4 subjects, the Gore-Tex patch was implanted to
      secure the "tension free" plasty; the Gore-Tex Dual Mesh was used in 2 subjects
      as well as the Gore-Tex Spinal. RESULTS: Two subjects, who had the Gore-Tex Dual
      Mesh implanted, developed sequestration of the implant during the late
      postopertive period. Upon reoperation, the authors removed the Gore-Tex Dual Mesh
      in the both subjects. However, they found a firm fibrous membrane, which was
      considered sufficient to protect the dural sac. On the contrary, the both
      subjects who had the Gore-Tex Spinal implanted, healed with no complications
      recorded. CONCLUSION: Based on the experience, the Gore-Tex Dual Mesh, although
      implanted lege artis, does not appear a suitable material for fascia replacements
      in open spina bifida plastic procedures. Further experience will give more
      evidence, whether Gore-Tex Spinal would be a suitable alternative, however, the
      courses in the 2 subjects have hitherto been encouraging.

PMID- 19110947
TI  - [Is the lower extremities amputation rate on decrease?].
AB  - In the past few years, rates of the lower extremity amputations for ischemia have
      been decreasing in some countries and many world regions. Surely, growing numbers
      of revascularization procedures contribute to the situation. In the Czech
      Republic, the amputation and large amputation rates are similar to those in the
      developed countries (45, resp. 24/100 000) (according to hospital data), as well
      as the numbers of surgical revascularizations. However, in our country, foot
      amputations are on increase, while numbers of major amputations do not decrease,
      probably as a result of the human age prolongation and fast increase of diabetes
      mellitus rates. The following prerequisites are required to improve the
      situation: primary prevention of atherosclerosis, building a network of vascular
      centres which are able to provide all modern revascularization methods. In
      cooperation with general practitioners, angiologists, diabetologists and other
      medical specialists, it is necessary to prevent most patients from developing
      critical extremity ischemia. If it develops, it should be diagnosed immediately
      and the revascularization procedure should be considered.

PMID- 19110948
TI  - [Appendicitis in pregnancy].
AB  - THE AIM OF THE STUDY was to highlight the problems related to acute appendicitis
      in pregnancy. We present our own experiences with the diagnostics and therapy of
      this surgical complication during gravidity. Nausea, vomiting and pain in lower
      right abdomen as symptoms of appendicitis are often confused with the I.
      trimester gravidity symptoms. The change of pain locality and the loss of somatic
      pain in the II. and the III. trimester cause diagnostic delay and increase the
      incidence of appendiceal perforation. In case of suspected appendicitis, when
      evaluating laboratory parameters, the common finding of leucocytosis during
      gravidity further complicates the differential diagnosis. In comparison to common
      population, ultrasonography in gravidity displays lower sensitivity and
      specificity. MATERIAL AND RESULTS: In the course of the last ten years, 9 gravid
      women in the age (25.6 +/- 3.9) underwent appendectomy in the 2nd surgical clinic
      FNLP in Kosice. This represents 0.6 percentage incidence of appendicitis of 1496
      patients operated because of this diagnosis. One of the patient turned out to be
      a case of negative appendectomy while the rest had histologically confirmed
      gangrenous (5x), phlegmonous (1x) and catarrhalis appendicitis (2x). Perforation
      was encountered in one patient. In the physical examination dominated pain in the
      right hypogastrium, nausea and subfebrility. The diagnostic success of USG
      examination reached 40%. In all gravid patients leucocytosis was found, including
      a negative appendectomy. The average duration from hospitalization to operation
      was 38 hours. No maternal or fetal loss was noted. CONCLUSIONS: Correct
      diagnostic and early surgical intervention prevents further fetal and maternal
      morbidity and mortality. Physical examination is important in differential
      diagnosis. Leucocytosis is not a predictive marker of appendicitis. Visualization
      of appendix through ultrasonography is rather difficult in the third trimester.

PMID- 19110949
TI  - [Thoracoscopic anatomical lung resection--lobectomy].
AB  - The authors bring their first experience with a purely endoscopic anatomical lung
      resection - lobectomy with mediastinal lymphadenectomy. At the department of
      surgery, Liberec Hospital, we have, so far, done 5 operations using this new
      technique. Once left superior lobectomy and 4 left inferior lobectomies were
      carried out. We describe the procedures and surgical tactics in thoracoscopic
      operations using modern staplers and haemoclips. The aim was to compare the
      results and benefits of purely endoscopic versus "classical" operations and to
      dismantle the myth of the extreme finacial intensiveness of this procedure.

PMID- 19110950
TI  - [Isolated intraperitoneal rupture of the urinary bladder following a blunt
      abdominal trauma--a case review].
AB  - Isolated urinary bladder rupture is a uncommon injury. Authors are presenting the
      case of isolated intraperitoneal bladder rupture caused by blunt trauma of
      abdomen. This report describes assessment of this type of trauma and compares it
      with references. Due to early obtaining of exact diagnosis and following
      operative treatment no complications were in this case.

PMID- 19110951
TI  - [News in the lower extremity veins morphology].
AB  - This comprehensive article notifies on the latest information concerning the
      morphology of the lower extremity veins, including their anatomical terminology.
      As a consequence of vehement development of the diagnostic and therapeutic
      techniques, the more detailed knowledge of anatomy, terminology, venous system
      variants and venous wall structure is necessary both for the phlebologists,
      sonographists and for the surgeons and cardiosurgeons. The histological part
      brings information about the content of collagen and elastin fibers in all layers
      of the superficial veins wall and about the arrangement of the vasa vasorum in
      both normal and varicose vena saphena magna. The anatomical-terminological part
      enlightens the variability of the superficial venous system of the lower
      extremity and the completion of the terminology of some superficial and deep
      veins, veins of the pelvis and perforating veins. The simple and clear anatomical
      terminology is the base for easy and non-problematic communication and discussion
      between inland and foreign specialists.

PMID- 19110952
TI  - [Later age diaphragmatic hernia].
AB  - INTRODUCTION: Congenital diaphragmatic hernia (CDH) is usually diagnosed
      antenatally or through the neonatal period at present. It is also used to treat
      and manage CDH in this date. However in rare cases CDH could be presented after
      finished neonatal period with non-specific and misleading symptoms. The aim of
      our presentation is to analyze the patients with late - presenting and diagnosed
      CDH. METHODS: During period 1996-2006 we operated on 54 children with CDH, 12 of
      them with late - presenting CDH, age variance was 9 months and 6 years. The
      spectrum of symptoms was from asymptomatic CDH (2 patients), mild respiratory (4
      patients) and gastrointestinal symptoms (4 patients), combination of respiratory
      and gastrointestinal symptoms (2 patients) and finally the symptomatology of
      bowel incarceration (2 patients). RESULTS: Seven children presented with another
      associated malformations (m. Down, congenital heart failure, hydrocephalus,
      anorectal atresia). All 12 patients were operated on with a good results. The
      operation was composed of reposition of the herniated part of gastrointestinal
      tract (without need of resection) and diaphragmatic plastic. Two patients were
      reoperated on - once because of diaphragmatic relaxation and the second one due
      to consecutive heart operation. CONCLUSION: Congenital diaphragmatic hernia could
      be presented with chronic and non-specific respiratory or gastrointestinal
      symptoms. Time to time, presentation of diaphragmatic hernia as "acute abdomen"
      could be seen. The operation is indicated, also in asymptomatic patients as a
      prevention of life-threating events.

PMID- 19110953
TI  - [The solution of stress urinary incontinence in women by the TVT-S surgical
      method--correlation between the curative effect of this method and changes in
      ultrasound findings].
AB  - OBJECTIVE: The aims of this study were to compare ultrasonographic findings of
      the urethra and the tape position and mobility following the tension-free vaginal
      tape secure system (TVT-S) procedure and to correlate these data with clinical
      signs of cure and failure of this procedure in the treatment of stress urinary
      incontinence (SUI) in women. Another aim of our study was to determine
      indications for particular position of the tape (the "hammock" or "U" position)
      based on ultrasonographic findings of the urethra and the tape position following
      TVT-S. DESIGN: Prospective, randomized study. SETTINGS: Department of Gynecology
      and Obstetrics, First faculty of Medicine, Charles University and General
      Teaching Hospital, Prague. MATERIALS AND METHODS: Analyses of the position of the
      urethra and the tape of 85 patients were performed using perineal
      ultrasonography. The efficacy of the TVT-S procedure was evaluated by cough test
      and by the International Consultation on Incontinence Questionnaire - Short Form
      (ICIQ-UI SF). RESULTS: Objective assessment by cough test showed that 53 (62%) of
      our patients were completely dry, and in 32 (38%) patients leakage of urine
      persisted after the operation. From the US examination and results we can
      conclude that 3 months after the operation the mobility of the urethra and
      bladder neck are restricted. A correlation between cure effect and the
      restriction of the movement of the urethra was found between the position at the
      middle of the urethra before and after the operation. Subjective assessment of
      the cure effect of this operation by the ICIQ-UI SF questionnaires (n=81) showed
      that 39 (48%) of our patients were completely dry and 24 (30%) of patients
      improved, which means that in 42 (52%) patients leakage of urine persists after
      the operation. There are differences in the restriction of urethral mobility
      between the cured patients and those where leakage persisted. The middle of the
      urethra and UVJ are more restricted in movement in cured patients. We found no
      statistically significant differences between the US measurements of the position
      of the urethra of patients with the tape in the "hammock" and the "U" position.
      The only statistically significant difference found is a slightly higher tension
      of the "U" tape three months after the operation during the Valsalva maneuver;
      the median width of the tape in the "hammock" position is 10.1 mm, while in the
      "U" position it is 8.1 (Wilcoxon test p = 0.0056). There were six patients
      diagnosed with urgency de novo, without urge incontinence in this series. In
      seven cases we found vaginal erosion. CONCLUSIONS: From the US examination and
      results we can conclude that after the TVT-S operation, mobility of the urethra
      and bladder neck is restricted. After comparing ultrasonographic findings of the
      urethra and the tape position following TVT- Secure we can determine that there
      is no certain indication for placement of the tape in the "hammock" or the "U"
      position. The cure effect for different positions of the tape is similar. In some
      respects the slightly higher tension of the tape in the "U" position suggests
      that this tape position may be preferred in patients with intrinsic sphincter
      defect (ISD) of the urethra. A comparison of the cure effect of the TVT-S
      procedure with other tape procedures suggests a lower cure effect of this
      operation.

PMID- 19110954
TI  - [Long-term low molecular weight heparin protection during pregnancy for the
      recurrent fetal loss].
AB  - Recurrent fetal loss affects 1 to 5% women of the fertile age all over the world.
      Pathogenesis of recurrent early or late fetal loss remains unclear and therefore
      the LMHW administration during pregnancy has not been sorted out so far. Our
      trial deals with a cohort of 51 pregnant women with recurrent fetal loss in their
      personal history treated by long-term administration of LMWHs which was compared
      with a cohort of healthy women LMWHs untreated. 91% effectiveness of a long-term
      LMWH protection means in fact 43 liveborn babies delivered without any
      complications during pregnancy and delivery to 47 women - 30 of these women were
      primiparas.

PMID- 19110955
TI  - [Ductus venosus Arantii in the fetal venosus circulation: anatomical and clinical
      aspects].
AB  - OBJECTIVE: The purpose of this study was to summarize the published data on the
      anatomical structure of the ductus venosus, the mechanism of regulation of the
      ductus venosus shunting and its role in the fetal survival and the possible use
      of the measurement of the ductus venosus shunting in the clinical practice.
      DESIGN: Review. SETTING: Department of Obstetrics and Gynecology Medical Faculty
      Charles University Hradec Kralove. METHODS: We summarized published data on the
      ductus venosus shunting in the fetal venosus circulation with the regulatory
      mechanisms, doppler ultrasound diagnostic methods and the medical importance.
      CONCLUSION: The present review summarizes the results of clinical and
      experimental research on the ductus venosus in the fetal circulation.

PMID- 19110956
TI  - [2200 g-weight-fibroid: abdominal mymectomy in the twentieth week of pregnancy].
AB  - OBJECTIVE: To present our clinical experience with a case of myomectomy of very
      big myoma during the second trimestr of pregnancy and to analyse current articles
      with this topics. Two myomectomies in one pregnancy (in the second trimestr and
      during the cesarian section) are presented. DESIGN: Review article, case report.
      RESULTS: A case report of 36-years-old nulliparous woman with 2 big fibroids in
      pregnancy is presented. The pregnancy was troubleless until 20th week, than she
      was hospitalized with suddenly appeared pain in epigastrium. A big necrotisis of
      fibroid was found during the examination. The clinical situation of the pacient
      rapidly deteriorated - in 24 hours the pain increased and ileus appeared. The
      operation due to vital indication was carried out with maximal effort to preserve
      the pregnancy. The 2200g-weigh-myoma was removed abdominally and the pregnancy
      continued without another complication. The cesarian section was done in 38-week
      old pregnancy and a healthy child was delivered. The second big fibroid on the
      back of the uterus was found during the cesarian section, myomectomy and large
      adhesiolysis was done. The pacient was hospitalized during the puerperium again
      with reapperance of ileus. The therapy of ileus was conservative. A case report
      presents a rare ocurence of big myomectomy during the second trimestr of
      pregnancy which was complicated by recidivans ileus due to large adhesive process
      in abdominal cavity. CONCLUSION: The prevalence of fibroids in pregnancy is
      between 2 and 4%, only 10 procents of this pregnancies are complicated, the
      necrosis of fibroid during the pregnancy is one of the most difficult cases.

PMID- 19110957
TI  - [Vaginal and postpregnancy inflamations, risks of their treatment for fetus].
AB  - OBJECTIVE: Paper describes risks of gynaecological inflamations and their
      treatment for the successful course of pregnancy. DESIGN: Review. SETTING: Czech
      Teratology Information Service, 3. LF UK, Praha. SUBJECT AND METHODS: The article
      refers the most common types of vaginal inflamation and gives recommendation for
      the appropriate treatment that is safe for embryo or fetus according to advice of
      Teratology Information Service. CONCLUSION: Vaginal inflamation during pregnancy
      represents risks of abortion, miscarriage or prematurity. For the treatment, we
      have to take in consideration the age of pregnancy and we should use the drugs,
      that are safe during this period. It is necessary always to compare risks
      resulting from disorder and from drugs used.

PMID- 19110958
TI  - [Inactivation of BRCA1, BRCA2 and p53 genes in sporadic ovarian cancer].
AB  - OBJECTIVE: To analyze loss of heterozygosity (LOH), loss of expression and
      somatic mutations of BRCA1, BRCA2 and p53 genes in sporadic epithelial ovarian
      cancer samples. DESIGN: Original paper. SETTING: Oncogynecologic center, Clinic
      of Obstetrics and gynecology, First Faculty of Medicine, Charles University in
      Prague and General Teaching Hospital, Prague. MATERIAL AND METHODS: We used
      genomic DNA and total RNA from peripheral blood and fresh frozen tumor as a
      template for LOH, loss-of-expression and mutation analyses. RESULTS: LOH in at
      least one region was found in 60% of tumors. Majority of these alterations
      occurred not solely, but in conjunction with other region deletions. CONCLUSION:
      Our study confirms high frequency of somatic alteration of BRCA1, BRCA2 and p53
      genes in sporadic epithelial ovarian cancer.

PMID- 19110959
TI  - [Caesarean section--indication or choice?].
AB  - Currently, caesarean section is the most commonly indicated procedure. The
      proportion of caesarean deliveries continues to rise. And the spectrum of
      surgical indications has dramatically broadened. This contemplation is focused on
      the general outcome of surgical indications. The procedure is indicated on the
      basis of scientific evidence only in a limited manner, more often it is indicated
      on the basis of empiric results and significant subjective motivation of the
      participants - the indicating physician and pregnant patient. There is
      insufficient proof to conclusively demonstrate an increased or decreased risk of
      elective caesarean section as compared to a trial of labor. Thus making it
      ethical and professionally acceptable to perform a caesarean section based on the
      wish of a competent and well-informed pregnant woman.

PMID- 19110960
TI  - [Myomas, fertility and pregnancy].
AB  - OBJECTIVE: The objective of this paper is give to guideline to the management of
      myoma, fertility and pregnancy. DESIGN: Review. SETTING: Czech Society
      Gynecological Endoscopy. MATERIAL AND METHOD: The bibliographic data from Medline
      were reviewed from literature using the key words: fibroid - fertility -
      pregnancy. CONCLUSION: The clinical guidline was preparared after the aalysed
      data were supplied using the material of CSGE.

PMID- 19110961
TI  - [Orbital tumors in adults--a 10-year study].
AB  - The authors refer about diagnostic procedures, treatment and follow-up of 87
      adult patients with orbital tumors during the period 1998 - 2007 in the
      Department of Ophthalmology, Faculty Hospital Kralovske Vinohrady, Charles
      University, Prague, Czech Republic, E.U. The group consists of 42 men and 45
      women, age range 18-89 years. In 49 patients, the tumors were of benign origin
      (age 18-80 years, median, 48 years), and 38 patients suffered from malign tumors
      (age 38-89 years, median, 61 years). Among basic examinations methods ranked the
      magnetic resonance imaging and the histological verification of the tumor. Sixty
      four tumors were treated by means of 70 surgical procedures. The anterior
      diagnostic or therapeutic orbitotomy was used in 72.5% of the cases, lateral
      osteoplastic orbitotomy (Kronlein) in 14.5%, and exenteration of the orbit in 13%
      of the cases. Altogether 23 patients were treated without surgery by means of
      corticosteroids, or are followed-up due to a benign tumor only. As the most
      common, the inflammatory pseudotumors of the orbit were diagnosed in 40%.
      Clinically they were of the anterior nodular, or posterior diffuse form,
      dacryoadenitis or orbital myositis. All patients were treated by means of
      prednisolon for at least three months; due to the relapse of the immunopathologic
      process, in 16 % of the cases the therapy was supplemented with azathioprime. The
      surgical procedure was the choice of treatment in 66% of inflammatory processes
      in the lacrimal gland region. In four cases the sarcoidosis was established.The
      second tumor in the final ranking was lymphoma in 19.5%; the MALT-lymphoma was
      diagnosed in 59% of these cases. The chemotherapy was chosen for the treatment in
      2/3 of the cases, and in all cases the remission was reached.The actinotherapy
      was chosen especially in other types of lymphoma; the follicular form and
      "molding" lymphoma were the causes of the death in two patients. Among malignant
      tumors, the most serious clinical courses were histological different primary
      carcinomas of the orbitopalpebral region in 14% of the cases, and secondary
      melanoma spreading from the conjunctiva in 5.5%. Both these tumors, counting the
      same number as lymphomas, were the only indications to the exenteration of the
      orbit, and causes of the death in four patients. CONCLUSION: Among orbital tumors
      in adults, the most common were inflammatory pseudotumor and lymphoma. The
      decisive procedure was always the histological verification, which directed the
      following therapy.

PMID- 19110962
TI  - [Optical coherence tomography in benign and malignant melanocytic tumors].
AB  - PURPOSE: To investigate the input of optical coherence tomography (OCT) in
      evaluation of tissue changes in small choroidal melanocytic lesions. METHODS: We
      reviewed charts of 20 patients with uveal melanocytic tumors (9 with benign
      lesions and 11 with malignant ones). The best-corrected visual acuity (BCVA) was
      of 1.0-0.1 in the benign lesions and of 1.0-0.07 in the malignant ones at the
      time of presentation. Both fundi were examined after pupil dilatation using an
      indirect ophthalmoscope and a Goldmann lens.The tumor and the macula were
      captured and the ultrasound (US) was performed in all patients. Height of the
      tumor was of 1.3-1.7 mm in the benign lesions and of 1.40-2.8 mm in the malignant
      ones at presentation. The OCT scans have been placed to document the apex, the
      slope and the base of the tumor and the macula. The retinal thickness at the
      fixation point (RTFP) and the macular volume were of 140-357 microm and 6.1-7.6
      mm3 respectively in benign lesions, and of 173-680 microm and 5.9-14.4 mm3
      respectively in malignant ones at the presentation. Fluorescein angiography was
      indicated in 9 patients and indocyanine green in 8 of them.The follow-up period
      varied between 6 and 24 months in benign lesions and from 6 to 48 months in
      malignant ones. The following methods were used when indicated: laser
      photocoagulation, photodynamic therapy with verteporfin, brachytherapy, Leksell
      Gamma Knife irradiation, enucleation or combination of them. RESULTS: The BCVA
      remained the same in the benign lesions but worsened to 0.8-0 in the malignant
      ones; the height of the tumor on US did not change in benign lesions and measured
      of 1.4-2.8 mm in malignant ones; RTFP and macular volume on OCT were of 156-412
      microm and 7.1-8.2 mm3 respectively in benign lesions and of 124-506 microm and
      3.8-8.8 mm3 respectively in malignant ones at the last visit. Qualitative
      analysis included the presence of subretinal and intraretinal fluid, convex
      deformity of the scan, increased reflectivity of the retinal pigment epithelium
      (RPE) or the choroid and disruption of the RPE. CONCLUSION: It seems that OCT is
      one of the most important examination methods to distinguish small choroidal
      melanocytic lesions to be benign or malignant. OCT findings play important role
      to detect the active lesion that requires treatment before it starts to grow. It
      is needed to enlarge our study group and to increase its follow-up period.

PMID- 19110963
TI  - [Intraoperative floppy iris syndrome versus lens-iris diaphragm retropulsion
      syndrome].
AB  - Intraoperative floppy iris syndrome (IFIS) as well as lens-iris diaphragm
      retropulsion syndrome (LIDRS) may negatively influence the course of the modern
      cataract procedure. In case of simultaneous presence of both syndromes, the LIDRS
      may paradoxically ease the surgery by means of partial or transient elimination
      of the IFIS. It causes the dilatation of the pupil, pushes the iris back, and
      deepens the anterior chamber and this way reduces the fluttering of the iris and
      makes possible to perform important phases of the surgery, during that we are
      working in the proximity of the pupil. In case of coincidence with the IFIS,
      after the spontaneous interruption of the LIDRS, we can repeatedly induce it by
      means of switching the irrigation off and after shallowing of the anterior
      chamber by turning the irrigation on again.

PMID- 19110964
TI  - [The treatment of the rubeosis of the iris and the neovascular glaucoma in
      proliferative diabetic retinopathy by means of anti-VEGF].
AB  - The rubeosis of the iris is a serious complication especially in diabetic
      retinopathy and retinal veins occlusion. Cytokines, especially the vascular
      growing factor (VEGF), are responsible for the forming of new vessels. The
      treatment that inhibits the effect of the VEGF presents new possibilities in the
      neovascular diseases treatment. Bevacizumab (Avastin) is an anti-VEGF antibody
      that blocks all forms of VEGF-A. In three eyes with proliferative diabetic
      retinopathy and neovascularization of the iris and the anterior chamber angle,
      the dose of 1.25 mg of Avastin was applied intravitrealy. Just one week after the
      application of the drug, the decrease of the leakage on the iris, and the total
      disappearance of the neovascularization in three weeks were visible on the
      fluorescein angiogram. The recurrence of the neovascularization was found in one
      eye after three months and the treatment had to be repeated. Nine months after
      the second application, the disease is stabilized without the neovascularization.
      The intraocular pressure was elevated in two eyes before the application of
      Avastin, and was refractive to the treatment. After the disappearance of the
      neovascularization, the intraocular pressure was normalized and it was possible
      to terminate the antiglaucomatous therapy. The bevacizumab intravitreal treatment
      of the neovascularization of the iris and the anterior chamber angle was proved
      to be efficient, the neovascularization disappeared and the intraocular pressure
      was normalized. There were no side effects after the bevacizumab applications in
      any of our patients.

PMID- 19110965
TI  - [The intravitreal application of the tissue plasminogen activator in the
      treatment of submacular hemorrhage--a case report].
AB  - The authors present the possibility to influence therapeutically the submacular
      hemorrhage caused by age-related macular degeneration in the presence of
      choroidal neovascular membrane by means of recombinant plasminogen tissue
      activator (rt-PA) and expansive gas intravitreal injection followed by pneumatic
      relocation of the hemorrhage out of the foveolar region. The therapy is presented
      in a case report. The submacular hemorrhage without treatment causes serious
      decrease of visual functions. The human recombinant plasminogen tissue activator
      that is a glycoprotein, activating the transformation of plasminogen directly to
      plasmin has a trombolytic effect. Rt-PA is activated by binding to fibrin with
      high affinity. This minimally invasive procedure gives the possibility to treat
      this prognostic unfavorable finding, so after the lysis and pneumorelocation of
      the hemorrhage from the macular region we can treat the choroidal neovascular
      membrane.

PMID- 19110966
TI  - [Subjective examination of the nerve fiber layer of the retina and its evaluation
      in a healthy eye and in glaucoma].
AB  - The authors describe the advantage of subjective examination of the nerve fiber
      layer in everyday outpatient praxis of the ophthalmologist. The objective
      examination of the nerve fiber layer is performed on specialized clinics by means
      of expensive instruments as are OCT, GDX or HRT. Every ophthalmologist may
      analyze the retinal nerve fiber layer subjectively with the basic equipment of
      the praxis. The aim of this paper is to present a recommendation how to expand
      the routine technique of the direct ophthalmoscope examination and biomicroscopy
      examination on the slit lamp, to make possible to observe subjectively the
      retinal nerve fiber layer and to distinguish its changes in glaucoma.

PMID- 19110967
TI  - [Thrombolysis in central retinal artery occlusion using alteplase].
AB  - AIM: The systemic acute thrombolysis (fibrinolysis) is one of methods how to
      treat occlusion of the central retinal artery. We present our first results of
      this rarely used treatment. MATERIAL AND METHODS: The patients were treated by
      means of i.v. infusion of the fibrinolytic alteplasis (plasminogen tissue
      activator, Actilyse) with the dose 0.9 mg/kg of body weight, first as a bolus of
      10% of the dose, the rest was slowly applied while monitoring vital functions and
      coagulations parameters. The contraindications of the thrombolysis are especially
      tumors, bleeding, any surgery in last three months, and the brain stroke in the
      medical history, and diseases of the liver and kidneys. From November 2006 to
      April 2007, we treated 5 patients by means of thrombolysis; two patients with the
      occlusion of the temporal branch retinal artery (BRAO) with characteristic
      quadrant scotoma of the visual field and decrease of the visual acuity, and three
      patients with central retinal artery occlusion or hemi-occlusion (CRAO). RESULTS:
      The central visual acuity improved in all patients the next day after the
      thrombolysis. Both patients with the branch retinal artery occlusion had visual
      acuity 1.0, the delay between the thrombosis and the treatment was more than 12
      hours. In two out of three patients with the central occlusion the visual acuity
      improved from practical blindness to 0.66. The third patient came with the
      latency of more than 30 hours; he registered partial improvement shortly after
      the thrombolysis, but later, the visual acuity decreased again. CONCLUSION: The
      thrombolytic treatment is definitely an advantage comparing to the conservative
      treatment. According to many contraindications and possible complications, it is
      necessary to select the eligible patient carefully. The treatment can be done on
      specialized in-patient department with the possibility to monitor vital functions
      and coagulations factors during the treatment as well as after it. In four out of
      five of our patients, the treatment finished with fast recovery of visual acuity
      almost to the normal.The effect of the treatment was good up to 18 hours after
      the occlusion; after 30 hours it was bad.

PMID- 19110968
TI  - [Modern treatment of wet-type macular degeneration].

PMID- 19110969
TI  - Incentives and remuneration systems in dental services.
AB  - The aim of this study was to examine the effects of an incentive-based
      remuneration system on number of individuals under supervision and on quality of
      public dental services in Norway. The basis for the study was a natural
      experiment in which all public dental officers in one county were given the
      opportunity to renegotiate their contract from a fixed salary contract to a
      combined per capita and fixed salary contract. Comprehensive data were collected
      before and after the change. A main finding is that the transition to an
      incentive-based remuneration system led to an increase in the number of
      individuals under supervision without either a fall in quality or a patient
      selection effect.

PMID- 19110973
TI  - Isolated acquired ACTH deficiency and primary hypothyroidism: a short series and
      review.
AB  - Idiopathic isolated ACTH deficiency, congenital or acquired, is rare. It may be
      found in association with primary hypothyroidism. Here we describe four cases of
      acquired idiopathic isolated ACTH deficiency illustrating its importance and
      variable presentation. All cases had a structurally normal pituitary gland and
      persistently normal residual pituitary function. Three cases had co-existing
      primary hypothyroidism. We discuss the protean presentation of this rare but
      important condition, its treatment, associations, and possible aetiologies.

PMID- 19110975
TI  - [Acute and chronic effects of electroconvulsive therapy on neuroactive steroids
      in patients with major depressive disorder].
AB  - OBJECTIVE: Baseline serum levels of neuroactive steroids such as
      dehydroepiandrosterone sulfate (DHEAS), 17-hydroxyprogesterone (17-OHP),
      testosterone, and cortisol were measured, and the acute and long-term effects of
      electroconvulsive therapy (ECT) on these hormones and the effect of gender on
      alterations in steroid hormones were investigated in patients with major
      depressive disorder (MDD). METHODS: The study included 25 inpatients (11 male, 14
      female) diagnosed with MDD that responded to ECT, and 37 healthy controls (17
      male, 20 female). Serum levels of cortisol, DHEAS, 17-OHP, and testosterone were
      measured 2 days before and 10 min after the first ECT, and 3 days after the last
      ECT in the patients. These measurements were obtained only once in the controls.
      RESULTS: Basal DHEAS increased, testosterone and 17-OHP decreased, and cortisol
      levels remained unchanged in MDD patients as compared to the controls. After
      completion of the therapeutic course of ECT, DHEAS levels in the patients were
      higher than they were before the treatment. After ECT treatment, cortisol and 17
      OHP levels in the patients were lower than those in the controls; however,
      testosterone levels did not differ between the groups. In the MDD patients,
      increases in DHEAS and decreases in testosterone were only observed in men, while
      decreases in 17-OHP were only seen in women. CONCLUSIONS: Alterations were
      observed in some neuroactive steroids in MDD patients and it appears that ECT
      affected these hormones. It is not clear whether the observed alterations in
      neuroactive steroids are associated with the pathophysiology of depression or
      whether they play a role in the therapeutic effects of ECT.

PMID- 19110970
TI  - Beta-adrenergic stimulation and myocardial function in the failing heart.
AB  - The sympathetic nervous system provides the most powerful stimulation of cardiac
      function, brought about via norepinephrine and epinephrine and their postsynaptic
      beta-adrenergic receptors. More than 30 years after the first use of practolol in
      patients with heart failure beta blockers are now the mainstay of the
      pharmacological treatment of chronic heart failure. Many aspects of their
      mechanism of action are well understood, but others remain unresolved. This
      review focuses on a number of questions that are key to further developments in
      the field. What accounts for and what is the role of beta-adrenergic
      desensitization, a hallmark of the failing heart? Is part of this adaptation
      predominantly beneficial and should therefore be reinforced, another part mainly
      maladaptive and therefore a target for antagonists? Which lessons can be drawn
      from studies in genetically engineered mice, which from (pharmaco) genetic
      studies? Finally, what are promising targets downstream of beta-adrenergic
      receptors that go beyond the current neurohumoral blockade?

PMID- 19110971
TI  - The role of thyroid hormone in the pathophysiology of heart failure: clinical
      evidence.
AB  - Thyroid hormone (TH) has a fundamental role in cardiovascular homeostasis in both
      physiological and pathological conditions, influencing cardiac contractility,
      heart rate (HR), diastolic function and systemic vascular resistance (SVR)
      through genomic and non-genomic mediated effects. In heart failure (HF) the main
      alteration of thyroid function is referred to as "low-triiodothyronine (T3)
      syndrome" (LT3S) characterized by decreased total serum T3 and free T3 (fT3) with
      normal levels of thyroxine (T4) and thyrotropin (TSH). Even if commonly
      interpreted as an adaptive factor, LT3S may have potential negative effects,
      contributing to the progressive deterioration of cardiac function and myocardial
      remodeling in HF and representing a powerful predictor of mortality in HF
      patients. All these observations, together with the early evidence of the
      benefits of T3 administration in HF patients indicate that placebo-controlled
      prospective studies are now needed to better define the safety and prognostic
      effects of chronic treatment with synthetic TH in HF.

PMID- 19110976
TI  - [Anticipation in bipolar disorder: A comparison between two generations].
AB  - OBJECTIVE: The genetic phenomenon of anticipation is a pattern of inheritance
      that includes earlier age at onset and increased severity of symptoms in
      succeeding generations, and is a feature of some neurodegenerative diseases. This
      phenomenon is suggested to occur in bipolar disorder (BP) as well. METHOD:
      Anticipation in children with BP type 1 (s2) (n = 31) and their parents (s1) (n =
      31) not-consecutive generations-was assessed by analyzing clinical
      characteristics and prognoses. RESULTS: Age at onset of BP type 1 in s2 (mean:
      19.3 +/- 4.2 years) occurred earlier than in s1 (mean: 29.5 +/- 10.2 years) (u =
      345, P < 0.001). There was a direct negative correlation between the s1 and s2
      cases (r = -0.554, P < 0.001). The total number of episodes in s1 (13.9 +/- 12.3)
      was greater than in s2 (8.7 +/- 7), which had a higher frequency of episodes (0.6
      +/- 0.3 and 1.5 +/- 1.2) (u = 357, P < 0.001). There was a direct correlation
      between total episodes and the frequency of manic episodes between s1 and s2 (r =
      0.312, P < 0.001 and r = 0.365, P < 0.001, respectively). We observed that 72.7%
      of BP type 1 parents that had episodes with psychotic features had offspring that
      had episodes with psychotic features. CONCLUSIONS: Results of this study show
      that age at onset was earlier and the frequency of episodes was greater in s2 BP
      type 1 cases. In addition, episodes with psychotic features might be a marker for
      genetic anticipation.

PMID- 19110977
TI  - [The effects of methylphenidate on various components of visual attention in
      children with attention-deficit hyperactivity disorder].
AB  - OBJECTIVE: Attention-deficit hyperactivity disorder (ADHD) is characterized by
      deficits and impairment in various components of visual attention.
      Methylphenidate (MPH) is the most commonly prescribed treatment for children with
      ADHD. The purpose of this study was to examine the effects of MPH on visual
      selective attention, sustained attention, and visual spatial attention in
      children with ADHD. METHOD: The study sample included 43 children (32 boys, 11
      girls: age range: 7-12 years) that met the DSM-IV criteria for ADHD and
      consecutively referred to the Child and Adolescent Mental Health and Psychiatry
      Department of Gulhane Military Medical School. ADHD was evaluated with the Child
      and Adolescent Behavior Disorders Screening and Rating Scale, and the Mini
      International Neuropsychiatric Intervention (MINI) was administered to exclude
      comorbid diagnoses. Visual selective attention and sustained attention were
      measured by verbal and non-verbal Cancellation Tests, while visual spatial
      attention was measured with the Line Orientation Test (LOT). RESULTS: MPH
      administration increased the number of correct target detections and decreased
      the number of omission and commission errors, and shortened the time required for
      completion on the verbal and non-verbal Cancellation Tests, and also produced a
      more systematic pattern on the organized letters and figures subtests. MPH
      administration also improved LOT performance. CONCLUSION: The findings show that
      MPH medication was associated with improved visual selective attention, sustained
      attention, and visual spatial attention in children with ADHD.

PMID- 19110978
TI  - [Hemodialysis patients' evaluation of their lives].
AB  - OBJECTIVE: The experience of end-stage renal failure (ESRF) should not be
      understood merely in terms of functional impairment and increases in emotional
      distress. It should be assessed in its own right. Qualitative research is
      necessary for describing patients' own experience of ESRF so that findings are
      not influenced by psychological theory. METHOD: The typical sampling method was
      used to select the sample, which consisted of 16 hemodialysis patients. Thematic
      analysis of patient interviews followed established conventions so as to ground
      the analysis in the data, rather than pre-existing ideas. RESULTS: Qualitative
      analysis identified different ways in which the patients evaluated their lives.
      The patients described the effects of ESRF on their lives primarily in terms of
      attitudes towards limitations, mixed feelings about caregivers, and changes in
      their own character. Caregivers were frequently described as supportive, but
      patients also perceived them as sources of distress and difficulty. ESRF and its
      treatment were reported to have worsened not only the patients' emotional states,
      but also aspects of their character; however, the effect of ESRF also involved
      the experience of positive changes in character. CONCLUSION: The present study
      provides a detailed systematic account of how hemodialysis patients evaluated
      their lives. Some of the findings provide details about how the psychological
      processes that have been previously reported operate in practice, which
      clinicians and researchers need to understand; however, some findings cannot
      readily be explained according to existing ideas. The findings, therefore,
      identify potential targets for educational intervention to improve patient
      adjustment.

PMID- 19110979
TI  - [The relationship between subjective sleep quality and aggression in male
      subjects with antisocial personality disorder].
AB  - OBJECTIVE: The aim of this study was to evaluate subjective sleep quality and to
      determine its relationship to aggression in male subjects diagnosed with
      antisocial personality disorder (APD). METHODS: The study included 125 male
      soldiers with APD that consecutively presented to the outpatient psychiatric unit
      of GATA Haydarpasa Training Hospital. A control group of 125 normal volunteers
      with no known medical or psychiatric disorders were selected from among male
      military personnel. The subjects were evaluated with an assessment battery, which
      included the Pittsburgh Sleep Quality Index and Aggression Questionnaire, during
      a semi-structured interview. RESULTS: The main finding was that more of the APD
      patients suffered from disturbed sleep quality than did the controls. Compared to
      the matched controls the APD patients had lower subjective sleep quality, longer
      sleep latency, shorter duration of sleep, less habitual sleep efficiency, more
      sleep disturbances, more use of sleeping medication, and a higher level of
      daytime dysfunction. In the APD group, elevated levels of aggression were also
      significantly correlated with impaired sleep quality. CONCLUSIONS: The present
      study provides support for a strong link between subjective sleep quality and
      aggression in APD. Recognition of sleep disturbances in APD patients is also
      relevant to the management of APD because effective strategies to improve sleep
      in this patient group might also lead to vast reductions in their aggressive
      behaviors.

PMID- 19110980
TI  - [Prevalence of and factors related to depression in high school students].
AB  - OBJECTIVE: The study aimed at investigating the prevalence of and factors related
      to depression in high school students. METHOD: A total of 805 (n = 367 girls; n =
      438 boys) first year students from three high schools in the city of Aydin filled
      in a self-report questionnaire that contained questions about socio-demographics,
      academic achievement and religious belief. It included also a depression rating
      scale, social support scale, problem solving inventory and an assertiveness
      scale. T-tests, chi-square tests, Pearson moment products correlation
      coefficients, and logistic regression analysis were used to analyze the data.
      RESULTS: 141 students (17.5%) scored on and above the cut-off point on the
      Children Depression Inventory (CDI). In the first regression analyses low self
      esteem, low grade point average (GPA) and low perceived social support from
      friends in boys, and low self-esteem, low paternal educational level and low
      social support from friends were the predictors of girls' depression. When self
      esteem scores were excluded, low GPA, low perceived social support from friends
      and family, and inefficient problem solving skills were predictors of depression
      in boys; low perceived social support from friends and family, low paternal
      educational level, and inefficient problem solving skills were the independent
      predictors of depression in girls. CONCLUSION: Depression is prevalent in high
      school students. Low self-esteem, low perceived social support from peers and
      family, and inefficient problem solving skills appears to be risk factors for
      adolescent depression. Low GPA for boys and low paternal education for girls were
      gender specific risk factors. Psychosocial interventions geared for increasing
      self-esteem, social support and problem solving skills may be effective in the
      prevention and treatment of adolescent depression.

PMID- 19110981
TI  - [Sexual behavior and sources of information about sex among male adolescents: An
      8-year follow-up].
AB  - OBJECTIVE: This study aimed to determine the changes over time in sexual attitude
      and behavior among adolescents, and to measure the effect of sources information
      about sex on these changes. METHOD: This study was conducted in 2 stages, the
      first in 1996 and the second in 2004. In all, 392 male tenth grade students (150
      in the first stage and 242 in the second stage) were evaluated. A personal
      information questionnaire developed by the authors was used to collect
      sociodemographic data, including sexual behavior, sexual attitude, and sources of
      information about sex. RESULTS: The findings show that there was a significant
      increase in intercourse and flirting behavior from 1996 to 2004, although no
      significant difference in masturbation was observed. Additionally, the number of
      male adolescents that reported family and pornographic films as their sources of
      information about sex increased 1.6-fold and 2.9-fold, respectively. A
      significant relationship between watching pornographic films and engaging in
      sexual intercourse was noted. CONCLUSION: The number of male adolescents age mean
      16, engaging in sexual intercourse increased between 1996 and 2004. Pornographic
      films were observed to be the most common source of information about sex and
      also predicted the probability of adolescents having sex. Findings that indicate
      the need for better and more accurate sources of information about sex. The
      availability of good quality information about sex is critical to the development
      of the sexual identity and mental health of male adolescents.

PMID- 19110982
TI  - [Assessment of the therapeutic alliance: reliability and validity of the Working
      Alliance Inventory].
AB  - OBJECTIVE: Recent trends in psychotherapy research indicate a growing interest on
      the conceptualization and assessment of the therapeutic alliance. Accordingly,
      this study aimed to examine the reliability and validity of the Turkish Working
      Alliance Inventory (WAI) (Horvath and Greenberg, 1989) Therapist and Client
      Forms. METHOD: In the first phase of the study, the scale was presented to 5
      judges, representing psychoanalytic, gestalt, and cognitive behavioral
      approaches, who then placed the subscale's items within the intended theoretical
      construct with a high degree of consensus. In the second phase, Therapists
      (N=21), from different theoretical traditions, filled out the WAI (Therapist
      Form) based on their sessions with their three patients (N=63). Patients also
      completed the WAI (Client Form). These evaluations by therapists and patients
      have been carried out for the third or following sessions. RESULTS: The internal
      validity of the scale was alpha = .96 for the Therapist Form and alpha = .90 for
      the Client Form. Factors analysis, conducted only for the Client Form, revealed
      that 3 factors were loaded in congruence with the original WAI. Considering the
      limited number of therapists participated in the study, factor analysis could not
      be conducted for the Therapist Form. CONCLUSION: As preliminary evidence, our
      findings suggest that the validity and reliability of the Turkish WAI were at
      acceptable levels for clinical and research settings.

PMID- 19110983
TI  - [The psychometric properties of the new Turkish generic health-related quality of
      life questionnaire for children (Kid-KINDL)].
AB  - OBJECTIVE: There are few health-related quality of life (HRQOL) instruments
      available that have been validated for use with Turkish children. The Kid-KINDL
      is a generic measure of children's (8-12 years) HRQOL, which contains 24
      categorical items that assess 6 dimensions (physical well-being, emotional well
      being, self-esteem, family, friends, and school). The Kid-KINDL is available in
      many languages. Following an elaborate translation procedure and cognitive focus
      group interviews, the Kid-KINDL was adopted into Turkish. This paper describes
      the psychometric properties of the new Turkish Kid-KINDL. METHODS: In total, 1918
      children aged 8-12 years at a school in Manisa completed the Kid-KINDL. A
      confirmatory approach was used for validity and reliability analysis. Using the
      Multi-trait/Multi-item analysis program (MAP) item-internal consistency and item
      discriminant validity were calculated to confirm the instrument's structure.
      Likert scaling assumptions were tested and confirmatory factor analysis (CFA) was
      applied as well. After modification of 2 unsatisfactory items the Kid-KINDL was
      administered to a different group of 84 randomly selected children and the
      analyses were repeated. RESULTS: Cronbach's alpha was 0.35-0.78 before and 0.54
      0.78 after the scales was modified. MAP-scaling success was 60%-100% before and
      90%-100% after the modification. CFA confirmed the Kid-KINDL structure for the
      original version (RMSEA = 0.077) was less than the modified version (RMSEA =
      0.059), although for the latter the sample was rather small. Floor effects were
      negligible, and ceiling effects reached 19%. CONCLUSION: The results indicate
      that the Turkish Kid-KINDL was a reliable and factorially valid assessment of the
      children's HRQOL. The modifications made to the 2 unsatisfactory items increased
      the psychometric quality of the scale.

PMID- 19110984
TI  - [Financial conflict of interest in clinical psychiatry studies: a review].
AB  - Pharmaceutical industry revenues from global pharmaceutical sales have increased
      7% to $602 billion in 2005. Approximately 15% of these revenues were spent on
      clinical research and drug development studies. Because of the huge budget
      allocated to research and development studies the number of studies being
      conducted by pharmaceutical companies has increased. The impact of the
      pharmaceutical industry on clinical trials has been affected by financial
      conflicts of interest between researchers and the industry. Conflict of interest
      refers to a situation in which it appears that a researcher's personal financial
      interest could significantly affect the design, conduct, and/or reporting of such
      research. Financial conflict of interest has been reported to be frequent in
      clinical trials in general medicine. It is estimated that 89%-98% of comparative
      drug treatment studies are funded by pharmaceutical companies. It was reported
      that favorable outcomes for the firms conducting these studies were significantly
      more common in industry-funded studies than in non-industry funded ones. These
      biased outcomes were due to conscious or unconscious decisions about the design,
      data analysis, and publishing of the studies. Biased outcomes of industry-funded
      studies have diminished the integrity of academic institutions, pharmaceutical
      companies, researchers, and scientific journals; therefore, various precautions
      have been taken in order to reduce the effect of conflict of interest on study
      outcomes. The aim of this review was to evaluate the effect of conflict of
      interest on outcomes in clinical psychiatry studies.

PMID- 19110985
TI  - IPLEX and the telephone game: the difficulty in separating myth from reality on
      the internet.

PMID- 19110986
TI  - Genetic studies of amyotrophic lateral sclerosis: controversies and perspectives.
AB  - The genetic causes of amyotrophic lateral sclerosis (ALS) are slowly being
      dissected out with the help of recent advances in genetic technology. Linkage
      studies and association studies examining candidate genes, candidate pathways,
      and genome-wide association have been used, based on direct sequencing and
      correlations between genetic variations. Copy number and microsatellite variants
      have also been examined, although the ideal methods for analysis are still being
      developed. In this review we examine the evidence for a genetic basis to ALS,
      discuss the challenges and difficulties faced and summarize the support for the
      reported genetic causes of ALS.

PMID- 19110987
TI  - High-flow priapism undergoing arterial embolization: review of literature
      following American Urological Association guideline on the management of
      priapism.
AB  - We report herein a case of a patient with high-flow priapism for whom a gelatin
      sponge was used as a temporary occlusive agent in arterial embolization,
      resulting in favorable outcome. The American Urological Association guideline on
      the management of priapism recommends using temporary occlusive agents. We
      reviewed all reports published after the introduction of this guideline to
      compare temporary and permanent occlusive agents in terms of symptom improvement
      and onset of erectile dysfunction. The rate of symptom improvement differed
      significantly between temporary and permanent embolizing materials, but no
      significant difference was apparent in the rate of erectile function improvement.

PMID- 19110988
TI  - Inflammatory bowel disease-related lesions in the duodenal and gastric mucosa.
AB  - OBJECTIVE: In 10-15% of patients with colorectal inflammatory bowel disease it is
      not possible to determine whether they have Crohn's disease or ulcerative colitis
      and they are therefore classified as having inflammatory bowel disease
      unclassified (IBDU) (formerly referred to as "indeterminate colitis"). The aim of
      this study was to determine whether upper endoscopy with biopsies could be a
      useful tool for diagnosing patients with colorectal inflammatory disease.
      MATERIAL AND METHODS: Fifty-two patients (14 colorectal Crohn's disease, 19
      ulcerative colitis, 6 IBDU, 8 microscopic colitis and 5 without IBD) were
      examined by upper endoscopy. Biopsies from gastric and duodenal mucosa were
      examined histologically and the frequency of focal cryptitides was estimated.
      Helicobacter pylori-positive patients were excluded. RESULTS: Focal cryptitides
      (sometimes called focally enhanced gastritis) were found in 8/14 of patients with
      Crohn's disease, 4/19 patients with ulcerative colitis, 2/6 patients with IBDU,
      2/8 of patients with microscopic colitis and in 2/5 patients without IBD.
      CONCLUSIONS: Focal cryptitides are more commonly found in gastric and/or duodenal
      mucosa in patients with colorectal Crohn's disease than in other patients. Upper
      endoscopy with mucosal biopsies contributes towards a diagnosis in patients with
      colitis.

PMID- 19110989
TI  - Examining the stability of Automated Neuropsychological Assessment Metric (ANAM)
      baseline test scores.
AB  - Computerized neuropsychological (NP) testing has evolved into an important tool
      for clinicians in the assessment of sport-related concussions. The importance of
      having a reliable baseline test score for comparison post concussion is critical;
      yet, the stability of these baseline measurements has not been well established.
      The purpose of this study was to examine the consistency of the measurements
      derived from the Automated Neuropsychological Assessment Metric (ANAM) test
      battery over a series of repeated trials, in an attempt to determine at what
      point the test scores stabilized. A cohort of 25 recreationally active collegiate
      students, free from mild head injury, volunteered for the study. Throughput score
      (measures of performance efficiency) stability was assessed for the computerized
      NP tests using intraclass correlation coefficients (ICCs). Average throughput
      scores for all five test trials were simple reaction time (SRT) = 235, matching
      to sample (MSP) = 41, continuous performance test (CPT) = 108, math processing
      (MTH) = 24, and Sternberg memory (STN) = 89, and these are within the range of
      those previously reported. Results show that all four of the ICCs were in the
      excellent range of agreement (i.e., > or = .75), and more importantly, the
      statistical comparisons of the ICCs show that there was no significant difference
      between the ICCs. Consequently, results serve to show that two time periods are
      sufficient to obtain stable NP results, and thus clinicians can feel comfortable
      relying on a two-score baseline test for follow-up comparison.

PMID- 19110993
TI  - Nobel Prizes 2008.

PMID- 19110995
TI  - A magnetoelectric effect in YMnO3 and HoMnO3.

PMID- 19110997
TI  - A selective cyclooxygenase-2 inhibitor prevents inflammation-related squamous
      cell carcinogenesis of the forestomach via duodenogastric reflux in rats.
AB  - BACKGROUND: Duodenal reflux causes inflammation-related squamous cell
      carcinogenesis in the forestomach of rats without any carcinogens. The aim of
      this study was to investigate the efficacy of a selective cyclooxygenase (COX)-2
      inhibitor, meloxicam, in preventing this carcinogenesis. METHODS: A series of 188
      rats underwent a surgical duodenogastric reflux procedure and were divided into 2
      groups. One group was given commercial chow (control group), and the other was
      given experimental chow containing meloxicam (0.3 mg/kg body weight/day)
      (meloxicam group). The animals were sequentially sacrificed at Weeks 20, 30, 40,
      50, and 60 after surgery. The forestomach was examined for the presence of
      carcinoma, the incidence of reflux-related morphological changes, COX-2
      expression, and its activity. RESULTS: At Week 60, squamous cell carcinoma
      developed in 8 of 21 animals (38%) in the control group, but none of 20 (0%) in
      the meloxicam group (P<.05). In addition, basal cell dysplasia developed in 19 of
      21 (90%) animals in the control group, but only 4 of 20 (20%) in the meloxicam
      group (P<.01). COX-2 immunoreactivity was predominantly detected in macrophages
      in the epithelial stroma. Compared with nonsurgical rats, RNA expression of COX-2
      in the epithelium was up-regulated, reaching peak at an early stage of Week 20 in
      both groups (P<.005). The expression of microsomal prostaglandin E synthase-1 was
      lower in the meloxicam group than in the control group. PGE2 production was
      significantly suppressed throughout the experiment in the meloxicam group
      compared with the control group (P<.005). CONCLUSIONS: Meloxicam was effective in
      preventing reflux-induced squamous cell carcinogenesis via an inflamed squamous
      epithelium.

PMID- 19110998
TI  - Diethyl maleate-induced oxidative stress leads to testicular germ cell apoptosis
      involving Bax and Bcl-2.
AB  - Testicular germ cell apoptosis is normally a continuous process throughout life.
      However, massive testicular germ cell loss is known to result from a wide variety
      of cellular stresses including toxicant exposure. Thus, the present study was
      aimed to investigate the mechanisms of germ cell loss under stress conditions
      following diethyl maleate (DEM) exposure. Stress conditions were generated in
      male Balb/c mice by depleting glutathione by DEM administration. The germ cell
      apoptosis was found to be increased as assessed by terminal deoxynucleotidyl
      transferase (TdT)-mediated deoxy-UTP biotin nick end labeling (TUNEL) staining,
      evaluation of histoarchitechture of testis, and germ cell numbers. It was found
      that the germ cell number was significantly reduced in DEM-treated sections. RT
      PCR was carried out to assess Bax/Bcl-2 mRNA expression levels.
      Immunohistochemistry of Bax and Bcl-2 revealed Bax activation. The prevalence and
      cellular localization of the above markers in testicular tissues of DEM-treated
      animals suggest the possible involvement of Bax/Bcl-2 in the male germ cell
      apoptosis.

PMID- 19110999
TI  - Piperine activates testicular apoptosis in adult rats.
AB  - Piperine, an alkaloid present in the fruits of commonly used spice pepper, is
      known to impair reproductive functions. In the present study, piperine was
      administered to adult male rats at the dose levels of 1, 10, and 100 mg/kg body
      weight for 30 days to evaluate its effects on the testis. A significant decrease
      in the activities of antioxidant enzymes superoxide dismutase, catalase,
      glutathione peroxidase, and glutathione reductase in the testis was observed at
      10 and 100 mg of piperine administration when compared with the controls. A dose
      dependent increase in lipid peroxidation and hydrogen peroxide generation was
      also observed. Sialic acid levels in the testis were also found to be decreased
      when piperine was administered at 10 and 100 mg dose levels. Immunofluorescence
      studies demonstrated a dose-dependent increase in caspase 3 and Fas protein in
      testicular germ cells after piperine treatment. These observations indicate that
      piperine induces oxidative stress and thereby triggers apoptosis in the testis,
      contributing to hampered reproductive functions.

PMID- 19111000
TI  - N-Nitrosodimethylamine changes the expression of glutathione S-transferase in the
      liver of male mice: The role of antioxidants.
AB  - The present study investigated the protective effect of gossypol, selenium, zinc,
      or glutathione (GSH) against dimethylnitrosamine (DMN)-induced hepatotoxicity in
      the livers of male mice. The expression and the activity of glutathione S
      transferase (GST), levels of GSH, and free radicals (malondialdehyde (MDA)), as
      well as the activity of glutathione reductase were determined after the treatment
      of mice for seven consecutive days with low or high doses of gossypol, selenium,
      zinc, or GSH. In experimental groups, DMN was administered as a single dose for 2
      h after the repeated dose treatments of mice for seven consecutive days with each
      antioxidant. DMN reduced the expression and inhibited the activity of GST.
      However, repeated treatments of mice with low-dose gossypol or high dose of
      either selenium or GSH followed by a single dose of DMN induced the expression
      and the activity of GST. In contrast, low-dose treatments of mice with zinc,
      selenium, or GSH followed by a single dose of DMN reduced the expression and the
      activity of GST compared to either control or DMN-treated groups. In addition,
      high-dose treatment with either gossypol or selenium markedly induced the levels
      of GSH compared to either control or DMN-treated groups. Interestingly,
      pretreatment of mice with high dose of either gossypol or selenium for seven
      consecutive days followed by a single dose of DMN decreased the levels of MDA,
      whereas DMN induced such levels. It is concluded that high dose of either
      gossypol or selenium is a stronger protector than zinc and GSH in ameliorating
      the toxic effects of DMN.

PMID- 19111001
TI  - Novel indoloquinoline derivative, IQDMA, inhibits STAT5 signaling associated with
      apoptosis in K562 cells.
AB  - N'-(11H-indolo[3,2-c]quinolin-6-yl)-N,N-dimethylethane-1,2-diamine (IQDMA), an
      indoloquinoline derivative, synthesized in our laboratory, has been demonstrated
      to be an effective antitumor agent in human leukemia cells. In the present study,
      treatment with IQDMA inhibited phosphorylation of epidermal growth factor
      receptor (EGFR), Src, Bcr-Abl, and Janus-activated kinase (JAK2) in a time
      dependent manner. IQDMA also degraded JAK2 protein. Moreover, signal transducer
      and activator of transcription 5 (STAT5) signaling were also blocked by IQDMA.
      However, IQDMA did not inhibit other oncogenic and tumor survival pathways such
      as those mediated by Akt and extracellular signal-regulated kinase 1/2.
      Furthermore, IQDMA upregulated the expression of p21 and p27 and downregulated
      the expression of cyclin D1, myeloid cell leukemia-1(Mcl-1), Bcl-X(L), and
      vascular endothelial growth factor (VEGF). Taken together, these results indicate
      that IQDMA causes significant induction of apoptosis in K562 cells via
      downregulation of EGFR, Src, Bcr-Abl, JAK2, and STAT5 signaling and modulation of
      p21, p27, cyclin D1, Mcl-1, Bcl-X(L), and VEGF proteins. Thus, IQDMA appears to
      be a potential therapeutic agent for treating leukemia K562 cells.

PMID- 19111002
TI  - Purification and characterization of a novel high molecular weight exotoxin
      produced by red tide phytoplankton, Alexandrium tamarense.
AB  - Our recent studies have demonstrated that the aqueous extract prepared from
      Alexandrium tamarense, a harmful red tide phytoplankton, showed cytotoxicity on
      Vero cells. In this study, the toxic substance was purified from the culture
      supernatant of A. tamarense. Based on the gel-filtration profile, the molecular
      mass of a purified toxin was estimated to be about 1,000 kDa. On sodium
      dodecylsulfate-polyacrylamide gel electrophoresis (SDS-PAGE) analysis, a main
      band with molecular mass of 1,000 kDa was detected with periodic acid-Schiff
      (PAS) staining, but no protein bands were detected by Coomassie brilliant blue
      (CBB) protein staining. Sugar composition analysis of the toxin suggested that
      the toxin contains galactose, fucose, mannose, N-acetylglucosamine, xylose, and
      other minor saccharides, whereas no significant levels of amino acids were
      detected by amino acid analysis. These results suggest that the toxin is a
      polysaccharide-based compound. The toxin showed cytotoxic effects on various cell
      lines in a concentration-dependent manner. Among the cell lines tested, U937
      cells were the most susceptible to the toxin. In U937 cells treated with the
      toxin, a typical apoptotic nuclear morphological change and DNA fragmentation
      were observed. This is the first report demonstrating that a polysaccharide-based
      toxin isolated from red tide phytoplankton can induce apoptotic cell death.

PMID- 19111003
TI  - The role of nuclear factor-kappaB in rats of radiocontrast-media-induced
      nephropathy.
AB  - This study was undertaken to examine the possible role of the DNA-binding
      activity of nuclear factor-kappa B (NF-kappaB) in rat of radiocontrast-media
      induced nephropathy (RCIN) and to explore the characteristic of RCIN in rats and
      the role of NF-kappaB in its occurrence. Forty-eight adult male Sprague-Dawley
      (SD) rats were randomly divided into Groups A-D. Rats of Groups A and B were
      intravenously injected with NG-nitro-L-arginine methyl ester (L-NAME) (10 mg/kg)
      and indomethacin (10 mg/kg), respectively. Rats of Groups C and D were
      intravenously injected with 1-M phosphate buffer (PH = 8.4 3 mL/kg) and normal
      saline (NS 2 mL/kg), respectively. After 30 min, Groups A and D were injected
      with NS (8 mL/kg) and Groups B and C were injected with diatrizoate (DTZ 8
      mL/kg). After injected contrast media (CM) for 6 h, the serum creatinine and
      blood urea nitrogen of rat in Group B increased sharply as compared with Groups
      A, C, and D. After 48 h, the data recovered to 49.28 +/- 8.81 mumol/L and 6.72 +/
      2.75 mmol/L, respectively. Vacuolization of the tubule epithelial cells of the
      kidney was observed in Group A. Especially, these pathological changes were most
      obvious in outer medulla. Contrast to group A, the DNA-binding activity of NF
      kappaB in rat kidney of Group B reached a peak at the 6th h and recovered to the
      normal level after the 48th h. CM mainly damages renal tubular-interstitial,
      which appears the earliest and most serious in the outer medulla. Activation of
      NF-kappaB of renal may be one of the mechanisms of RCIN occurrence.

PMID- 19111004
TI  - Segment-specific proximal tubule injury in tripterygium glycosides intoxicated
      rats.
AB  - Tripterygium glycosides (TG), extracted from the Chinese herb Tripterygium
      wilfordii Hook. f, is a widely used anti-inflammatory and immunosuppressive agent
      with definite nephrotoxicity. However, its toxic mechanism remained undiscovered.
      The aim of this study was to characterize the potential toxicity of TG on
      segments of proximal tubule in rats. Six hundred and 1200 mg/kg of TG was
      administered by daily intragastric instillation for 16 days. A significant
      reduction of p-aminohippurate accumulation by renal cortical slices indicated
      that TG damaged organic anion transporter (OAT) system that localized at the
      proximal tubule, especially S(2) segment. A dramatic loss of kidney glutamine
      synthetase (GS) activity induced by TG reflected S(3) segment damage. Because
      mRNA expression of OAT1, OAT3, and GS was decreased substantially, we ascribe the
      fall of p-aminohippurate accumulation and GS activity to alterations at the
      transcriptional level. A dose-related diminution of kidney glutathione S
      transferase activity was noted simultaneously, suggesting oxidative stress
      involvement. Histopathological lesions were observed in the TG intoxicated rat
      kidney even though there were no obvious changes of serum urea and creatinine at
      this dose level. In summary, we provided evidences supporting that TG caused
      segment-specific dysfunction in the kidney proximal tubule.

PMID- 19111005
TI  - Isocyanates induces DNA damage, apoptosis, oxidative stress, and inflammation in
      cultured human lymphocytes.
AB  - Isocyanates, a group of low molecular weight aromatic and aliphatic compounds
      containing the isocyanate group (-NCO), are important raw materials with diverse
      industrial applications; however, pathophysiological implications resulting from
      occupational and accidental exposures of these compounds are hitherto unknown.
      Although preliminary evidence available in the literature suggests that
      isocyanates and their derivatives may have deleterious health effects including
      immunotoxicity, but molecular mechanisms underlying such an effect have never
      been addressed. The present study was carried out to assess the immunotoxic
      response of methyl isocyanate (MIC) on cultured human lymphocytes isolated from
      healthy human volunteers. Studies were conducted to evaluate both dose-dependent
      and time-course response (n = 3), using N-succinimidyl N-methylcarbamate, a
      surrogate chemical substitute to MIC. Evaluation of DNA damage by ataxia
      telangiectasia mutated (ATM) and gamma H2AX protein phosphorylation states;
      measure of apoptotic index through annexin-V/PI assay, apoptotic DNA ladder
      assay, and mitochondrial depolarization; induction of oxidative stress by CM
      H2DCFDA and formation of 8-hydroxy-2' deoxy guanosine; levels of antioxidant
      defense system enzyme glutathione reductase; and multiplex cytometric bead array
      analysis to quantify the secreted levels of inflammatory cytokines, interleukin
      8, interleukin-1beta, interleukin-6, interleukin-10, tumor necrosis factor, and
      interleukin-12p70 parameters were carried out. The results of the study showed a
      dose- and time-dependent response, providing evidence to hitherto unknown
      molecular mechanisms of immunotoxic consequences of isocyanate exposure at a
      genomic level. We anticipate these data along with other studies reported in the
      literature would help to design better approaches in risk assessment of
      occupational and accidental exposure to isocyanates.

PMID- 19111006
TI  - c-Jun N-terminal kinase signaling in the pathogenesis of nonalcoholic fatty liver
      disease: Multiple roles in multiple steps.

PMID- 19111007
TI  - Back to the future with noninvasive biomarkers of liver fibrosis.

PMID- 19111008
TI  - A transgenic mouse that reveals cell shape and arrangement during ureteric bud
      branching.
AB  - Understanding the cellular events that underlie epithelial morphogenesis is a key
      problem in developmental biology. Here, we describe a new transgenic mouse line
      that makes it possible to visualize individual cells specifically in the Wolffian
      duct and ureteric bud, the epithelial structures that give rise to the collecting
      system of the kidney. myr-Venus, a membrane-associated form of the fluorescent
      protein Venus, was expressed in the ureteric bud lineage under the control of the
      Hoxb7 promoter. In Hoxb7/myr-Venus mice, the outlines of all Wolffian duct and
      ureteric bud epithelial cells are strongly labeled at all stages of urogenital
      development, allowing the shapes and arrangements of individual cells to be
      readily observed by confocal microscopy of freshly excised or cultured kidneys.
      This strain should be extremely useful for studies of cell behavior during
      ureteric bud branching morphogenesis in wild type and mutant mouse lines.

PMID- 19111010
TI  - Novel method for the isolation of adipose stem cells (ASCs).
AB  - Adipose stem cells (ASCs) represent a cell population with great potential for
      tissue engineering applications. Several articles have been published showing the
      proliferation and differentiation potential, the markers and the wide range of
      potential applications of these cells. In the majority of these studies the ASCs
      are isolated using a basic enzymatic procedure, which results in a quite
      heterogeneous cell population that compromises their proliferation and
      differentiation. This paper reports the development and optimization of a new
      isolation/purification method that allows populations of ASCs to be obtained,
      which significantly reduces (and eventually eliminates) the 'contamination' of
      other cell types. This method is based on the use of immunomagnetic beads coated
      with specific antibodies. The first part of the study described here analysed the
      expression of marker genes for stem cells and the colony-forming unit (CFU)
      capacity of the cells isolated, while the second part is dedicated to the
      osteogenic differentiation potential of the isolated cells. The results showed
      that, using the isolation method based on immunomagnetic beads, it was possible
      to obtain ASCs and also underline the existence of several subpopulations of stem
      cells in the adipose tissue.

PMID- 19111009
TI  - Mapping of brain metabolite distributions by volumetric proton MR spectroscopic
      imaging (MRSI).
AB  - Distributions of proton MR-detected metabolites have been mapped throughout the
      brain in a group of normal subjects using a volumetric MR spectroscopic imaging
      (MRSI) acquisition with an interleaved water reference. Data were processed with
      intensity and spatial normalization to enable voxel-based analysis methods to be
      applied across a group of subjects. Results demonstrate significant regional,
      tissue, and gender-dependent variations of brain metabolite concentrations, and
      variations of these distributions with normal aging. The greatest alteration of
      metabolites with age was observed for white-matter choline and creatine. An
      example of the utility of the normative metabolic reference information is then
      demonstrated for analysis of data acquired from a subject who suffered a
      traumatic brain injury. This study demonstrates the ability to obtain proton
      spectra from a wide region of the brain and to apply fully automated processing
      methods. The resultant data provide a normative reference for subsequent
      utilization for studies of brain injury and disease.

PMID- 19111011
TI  - Sonographic determination of the position of a levonorgestrel intrauterine
      device.

PMID- 19111012
TI  - Frequency of ill-founded off-label prescribing in Dutch general practice.
AB  - PURPOSE: The aim of this study is to quantify the extent of ill-founded off-label
      drug prescriptions in Dutch general practice. The study is based upon information
      on both the prescription itself and the patient's medical history. METHODS: In
      total, 48 combinations of drugs and off-label indications were selected from a
      list of 477 known off-label combinations. These 48 combinations were considered
      as ill-founded since pharmacotherapeutic handbooks or clinical practice
      guidelines did not provide evidence for their efficacy and safety. They were
      considered to be relevant for investigation in general practice. We used a
      nationally representative information network of 85 general practices in the
      Netherlands. By using information on the patients' diagnoses and medication in
      the period before and after the prescription, we were able to exclude non
      conclusively off-label prescriptions. RESULTS: Twenty-one of the selected 48 off
      label combinations did not occur in Dutch general practice. The drugs with the
      highest proportion of ill-founded off-label prescriptions were betahistine
      (26.7%), celecoxib (16.3%) and etoricoxib (12.5%). In total, 18.2% of the
      prescriptions, which were initially assessed as ill-founded off-label, were re
      evaluated as on-label, after considering the patient's medical history.
      CONCLUSIONS: Ill-founded off-label prescribing in Dutch general practice is
      limited for 48 relevant combinations of drugs and off-label indications. In order
      to overcome limitations in registration databases, it is useful to look at as
      much information as possible--for example, co-medication and co-morbidity--when
      determining off-label prescribing. Studying ill-founded off-label prescribing
      should be performed on a day-to-day basis, especially for recently introduced
      drugs.

PMID- 19111013
TI  - Medication adherence, first episode duration, overall duration and time without
      therapy: the example of bisphosphonates.
AB  - PURPOSE: We aimed to determine the duration of first episode of therapy and
      overall therapy as well as time without treatment for bisphosphonates. METHODS:
      Data were extracted from Department of Veterans' Affairs (DVA) dataset for those
      with at least one dispensing for a bisphosphonate between April 2001 and April
      2007. Episodes of use were determined as the number of treatment days between the
      first and last prescription plus 35 days once a dispensing gap of 105 days had
      been reached, or where no treatment gaps were recorded, the study end date.
      Kaplan-Meier analyses were undertaken for the first episode of use, overall
      duration and time without treatment. RESULTS: When considering only the duration
      of first episode, median bisphosphonate use was 1.19 years. The median duration
      extended to 3.27 years when all episodes of use were considered. Overall, 52.0%
      of subjects reached at least 3 years of treatment and 66.5% of existing users had
      a duration of at least 3 years. Median time without treatment was 1.65 years.
      Overall, 81% of the cohort had enough medicine dispensed to be considered
      adherent throughout their duration of use. CONCLUSION: Over 50% of subjects and
      66% of existing users had duration consistent with the minimum recommended.
      Adherence within an episode was high. The focus for improving duration of
      bisphosphonate use should be on reducing the time without treatment, rather than
      adherence at the time of use. Studies assessing only the first episode of use in
      new users of medicines may underestimate duration.

PMID- 19111014
TI  - The Australian rise of esomeprazole-was expenditure on samples a contributor?
AB  - BACKGROUND: Administrative data from the Australian Pharmaceutical Benefits
      Scheme (PBS) showed rapid growth of esomeprazole dispensing when it was launched.
      Australia has universal prescription medicine coverage (the PBS), which included
      esomeprazole from August 2002. Free samples of new medicines are commonly
      provided to doctors. OBJECTIVES: To determine if a relationship exists between
      marketing expenditure on samples and the dispensing rate for esomeprazole in
      Australia between June 2002 and September 2006. METHODS: Quarterly sample
      expenditures at product/brand level for proton pump inhibitors (PPIs) for
      Australian general practitioners were obtained for July 2002 to September 2006.
      Corresponding PBS dispensing data were obtained for all PPIs and converted to
      defined daily dose (DDD)/1000 population/day. Spending on samples was calculated
      as dollars per dispensed prescription and plotted against time on the Australian
      market. RESULTS: Total PPI usage increased from 34.2 to 50.8 DDD/1000
      population/day over the study period. Expenditure on samples per dispensed
      prescription was higher when a PPI was new on the market and diminished over 5-6
      years to a relatively constant level. The rapid decline in this ratio was
      demonstrated by a case study following esomeprazole from launch in Australia for
      almost 5 years clearly demonstrating the initial investment to drive sales.
      CONCLUSION: A relationship appears to exist between expenditure on esomeprazole
      samples and its usage in Australia. A high initial investment was followed by a
      rapid reduction in cost per prescription dispensed, predominantly due to growth
      in market share. This trend was consistent with other PPIs.

PMID- 19111015
TI  - Potentially inappropriate medication for emergency department visits by elderly
      patients in Taiwan.
AB  - PURPOSE: The potential for adverse drug events caused by potentially
      inappropriate medication (PIM) use in elderly patients at emergency department
      (ED) visits is a growing concern. The objects of this study were to determine the
      prevalence, characteristics and risk factors of PIM use among elderly ED visits
      in Taiwan. METHODS: The nationwide computerized claims database of elderly ED
      visits under the National Health Insurance (NHI) in Taiwan during 2001-2004 was
      accessed. PIM, independent of diseases diagnoses or conditions and should be
      generally be avoided in elderly people, was evaluated using the updated 2003
      Beers criteria. RESULTS: Between 2001 and 2004, 14.7% of total 1 429 463 elderly
      ED visits with prescriptions had PIM, and 19.3% of elderly people who visited ED
      received at least one PIM annually. Odds ratio for PIM prescriptions to ED
      elderly was higher for visits at which more drugs were prescribed, visits at
      local community hospital, female and older physicians, patients aged 65-69 years
      and female patients. Common PIM categories were short acting nifedipine, muscle
      relaxants and anti-spasmodics, antihistamines and ketorolac. When health care
      resource utilization was compared in 2004, subjects receiving PIM at ED visit had
      significantly more mean ambulatory care visits, ED visits and hospital admissions
      than subjects who did not receive PIM. CONCLUSIONS: About one fifth of elderly
      people who visited ED received PIM annually in Taiwan. The public and physicians
      should be educated, and a computerized drug surveillance system might be needed
      to avoid PIM prescriptions to the ED elderly patients.

PMID- 19111016
TI  - Estrogens and the risk of complex regional pain syndrome (CRPS).
AB  - OBJECTIVE: Since complex regional pain syndrome (CRPS) shows a clear female
      predominance, we investigated the association between the cumulative as well as
      current exposure to estrogens, and CRPS. METHODS: A population-based case-control
      study was conducted in the Integrated Primary Care Information (IPCI) project in
      the Netherlands. Cases were identified from electronic records (1996-2005) and
      included if they were confirmed during a visit (using International Association
      for the Study of Pain Criteria), or had been diagnosed by a specialist. Controls
      were matched to cases on gender, age, calendar time, and injury. Measures of
      cumulative endogenous estrogen exposure were obtained by questionnaire and
      included age of menarche and menopause, menstrual life, and cumulative months of
      pregnancy and breast-feeding. Current estrogen exposure at CRPS onset was
      retrieved from the electronic medical records and determined by current pregnancy
      or by the use of oral contraceptive (OC) drugs or hormonal replacement therapy
      (HRT). RESULTS: Hundred and forty-three female cases (1493 controls) were
      included in analyses on drug use and pregnancies, while cumulative endogenous
      estrogen exposure was studied in 53 cases (58 controls) for whom questionnaire
      data were available. There was no association between CRPS and either cumulative
      endogenous estrogen exposure, OC, or HRT use. CRPS onset was increased during the
      first 6 months after pregnancy (OR: 5.6, 95%CI: 1.0-32.4), although based on
      small numbers. DISCUSSION: We did not find an association between CRPS onset and
      cumulative endogenous estrogen exposure or current OC or HRT use, but more
      powered studies are needed to exclude potential minor associations.

PMID- 19111017
TI  - Effect of polyI:C cotreatment on halothane-induced liver injury in mice.
AB  - Drug-induced liver injury (DILI) is a challenging problem in drug development and
      clinical practice. Patient susceptibility to DILI is multifactorial, making these
      reactions difficult to predict and prevent. Clinical observations have suggested
      that concurrent bacterial and viral infections represent an important risk factor
      in determining patient susceptibility to developing adverse drug reactions,
      although the underlying mechanism is not clear. In the present study, we employed
      the viral RNA mimetic (polyinosinic-polycytidylic acid [polyI:C]) to emulate
      viral infection and examined its effect on halothane-induced liver injury.
      Although pretreatment of mice with polyI:C attenuated halothane hepatotoxicity
      due to its inhibitory effect on halothane metabolism, posttreatment significantly
      exacerbated liver injury with hepatocellular apoptosis being significantly higher
      than that in mice treated with polyI:C alone or halothane alone. The pan-caspase
      inhibitor z-VAD-fmk suppressed liver injury induced by polyI:C/posthalothane
      cotreatment, suggesting that the increased hepatocyte apoptosis contributes to
      the exacerbation of liver injury. Posttreatment with polyI:C also caused
      activation of hepatic Kupffer cells (KCs) and natural killer (NK) cells and
      upregulated multiple proapoptotic factors, including tumor necrosis factor-alpha
      (TNF-alpha), NK receptor group 2, member D (NKG2D), and Fas ligand (FasL). These
      factors may play important roles in mediating polyI:C-induced hepatocyte
      apoptosis. CONCLUSION: This is the first study to provide evidence that
      concurrent viral infection can inhibit cytochrome (CYP)450 activities and
      activate the hepatic innate immune system to proapoptotic factors. DILI may be
      attenuated or exacerbated by pathogens depending on the time of infection.

PMID- 19111018
TI  - Low retinol levels differentially modulate bile salt-induced expression of human
      and mouse hepatic bile salt transporters.
AB  - The farnesoid X receptor/retinoid X receptor-alpha (FXR/RXRalpha) complex
      regulates bile salt homeostasis, in part by modulating transcription of the bile
      salt export pump (BSEP/ABCB11) and small heterodimer partner (SHP/NR0B2). FXR is
      activated by bile salts, RXRalpha by the vitamin A derivative 9-cis retinoic acid
      (9cRA). Cholestasis is associated with vitamin A malabsorption. Therefore, we
      evaluated the role of vitamin A/9cRA in the expression of human and mouse bile
      salt export pump (hBSEP/mBsep), small heterodimer partner (hSHP/mShp), and mouse
      sodium-dependent taurocholate co-transporting polypeptide (mNtcp). HBSEP and hSHP
      transcription were analyzed in FXR/RXRalpha-transfected HepG2 cells exposed to
      chenodeoxycholic acid (CDCA) and/or 9cRA. BSEP promoter activity was determined
      by luciferase reporter assays, DNA-binding of FXR and RXRalpha by pull-down
      assays. Serum bile salt levels and hepatic expression of Bsep, Shp, and Ntcp were
      determined in vitamin A-deficient (VAD)/cholic acid (CA)-fed C57BL/6J mice.
      Results indicated that 9cRA strongly repressed the CDCA-induced BSEP
      transcription in HepG2 cells, whereas it super-induced SHP transcription; 9cRA
      reduced DNA-binding of FXR and RXRalpha. The 9cRA repressed the CDCA-induced BSEP
      promoter activity irrespective of the exact sequence of the FXR-binding site. In
      vivo, highest Bsep messenger RNA (mRNA), and protein expression was observed in
      CA-fed VAD mice. Shp transcription was highest in CA-fed vitamin A-sufficient
      mice. Ntcp protein expression was strongly reduced in CA-fed VAD mice, whereas
      mRNA levels were normal. CA-fed control and VAD mice had similarly increased
      serum bile salt levels. CONCLUSION: We showed that 9cRA has opposite effects on
      bile salt-activated transcription of FXR/RXRalpha target genes. Vitamin A
      deficiency in CA-fed mice leads to high BSEP expression. Clearance of serum bile
      salts may, however, be limited because of post-transcriptional reduction of Ntcp.
      The molecular effects of vitamin A supplementation during cholestasis need
      further analysis to predict a therapeutic effect.

PMID- 19111020
TI  - The pathogen receptor liver and lymph node sinusoidal endotelial cell C-type
      lectin is expressed in human Kupffer cells and regulated by PU.1.
AB  - Human LSECtin (liver and lymph node sinusoidal endothelial cell C-type lectin,
      CLEC4G) is a C-type lectin encoded within the L-SIGN/DC-SIGN/CD23 gene cluster.
      LSECtin acts as a pathogen attachment factor for Ebolavirus and the SARS
      coronavirus, and its expression can be induced by interleukin-4 on monocytes and
      macrophages. Although reported as a liver and lymph node sinusoidal endothelial
      cell-specific molecule, LSECtin could be detected in the MUTZ-3 dendritic-like
      cell line at the messenger RNA (mRNA) and protein level, and immunohistochemistry
      analysis on human liver revealed its presence in Kupffer cells coexpressing the
      myeloid marker CD68. The expression of LSECtin in myeloid cells was further
      corroborated through the analysis of the proximal regulatory region of the human
      LSECtin gene, whose activity was maximal in LSECtin+ myeloid cells, and which
      contains a highly conserved PU.1-binding site. PU.1 transactivated the LSECtin
      regulatory region in collaboration with hematopoietic-restricted transcription
      factors (Myb, RUNX3), and was found to bind constitutively to the LSECtin
      proximal promoter. Moreover, knockdown of PU.1 through the use of small
      interfering RNA led to a decrease in LSECtin mRNA levels in THP-1 and monocyte
      derived dendritic cells, thus confirming the involvement of PU.1 in the myeloid
      expression of the lectin. CONCLUSION: LSECtin is expressed by liver myeloid
      cells, and its expression is dependent on the PU.1 transcription factor.

PMID- 19111021
TI  - Lymphotoxin-beta receptor signaling regulates hepatic stellate cell function and
      wound healing in a murine model of chronic liver injury.
AB  - Lymphotoxin-beta (LTbeta) is a proinflammatory cytokine and a member of the tumor
      necrosis factor (TNF) superfamily known for its role in mediating lymph node
      development and homeostasis. Our recent studies suggest a role for LTbeta in
      mediating the pathogenesis of human chronic liver disease. We hypothesize that
      LTbeta co-ordinates the wound healing response in liver injury via direct effects
      on hepatic stellate cells. This study used the choline-deficient, ethionine
      supplemented (CDE) dietary model of chronic liver injury, which induces
      inflammation, liver progenitor cell proliferation, and portal fibrosis, to assess
      (1) the cellular expression of LTbeta, and (2) the role of LTbeta receptor
      (LTbetaR) in mediating wound healing, in LTbetaR(-/-) versus wild-type mice. In
      addition, primary isolates of hepatic stellate cells were treated with LTbetaR
      ligands LTbeta and LTbeta-related inducible ligand competing for glycoprotein D
      binding to herpesvirus entry mediator on T cells (LIGHT), and mediators of
      hepatic stellate cell function and fibrogenesis were assessed. LTbeta was
      localized to progenitor cells immediately adjacent to activated hepatic stellate
      cells in the periportal region of the liver in wild-type mice fed the CDE diet.
      LTbetaR(-/-) mice fed the CDE diet showed significantly reduced fibrosis and a
      dysregulated immune response. LTbetaR was demonstrated on isolated hepatic
      stellate cells, which when stimulated by LTbeta and LIGHT, activated the nuclear
      factor kappa B (NF-kappaB) signaling pathway. Neither LTbeta nor LIGHT had any
      effect on alpha-smooth muscle actin, tissue inhibitor of metalloproteinase 1,
      transforming growth factor beta, or procollagen alpha(1)(I) expression; however,
      leukocyte recruitment-associated factors intercellular adhesion molecule 1 and
      regulated upon activation T cells expressed and secreted (RANTES) were markedly
      up-regulated. RANTES caused the chemotaxis of a liver progenitor cell line
      expressing CCR5. CONCLUSION: This study suggests that LTbetaR on hepatic stellate
      cells may be involved in paracrine signaling with nearby LTbeta-expressing liver
      progenitor cells mediating recruitment of progenitor cells, hepatic stellate
      cells, and leukocytes required for wound healing and regeneration during chronic
      liver injury.

PMID- 19111019
TI  - Liver stem cells and hepatocellular carcinoma.
AB  - Although the existence of cancer stem cells (CSCs) was first proposed over 40
      years ago, only in the past decade have these cells been identified in
      hematological malignancies, and more recently in solid tumors that include liver,
      breast, prostate, brain, and colon. Constant proliferation of stem cells is a
      vital component in liver tissues. In these renewing tissues, mutations will most
      likely result in expansion of the altered stem cells, perpetuating and increasing
      the chances of additional mutations and tumor progression. However, many details
      about hepatocellular cancer stem cells that are important for early detection
      remain poorly understood, including the precise cell(s) of origin, molecular
      genetics, and the mechanisms responsible for the highly aggressive clinical
      picture of hepatocellular carcinoma (HCC). Exploration of the difference between
      CSCs from normal stem cells is crucial not only for the understanding of tumor
      biology but also for the development of specific therapies that effectively
      target these cells in patients. These ideas have drawn attention to control of
      stem cell proliferation by the transforming growth factor beta (TGF-beta), Notch,
      Wnt, and Hedgehog pathways. Recent evidence also suggests a key role for the TGF
      beta signaling pathway in both hepatocellular cancer suppression and endoderm
      formation, suggesting a dual role for this pathway in tumor suppression as well
      as progression of differentiation from a stem or progenitor stage. This review
      provides a rationale for detecting and analyzing tumor stem cells as one of the
      most effective ways to treat cancers such as HCC.

PMID- 19111022
TI  - Fraud and dishonesty in "scientific" publication.

PMID- 19111023
TI  - Sardasht-Iran cohort study of chemical warfare victims: design and methods.
AB  - BACKGROUND: Insights into long-term clinical consequences of sulfur mustard have
      emerged from some investigations but less is known about the basic and molecular
      mechanisms of these complications. Sardasht-Iran Cohort Study is a comprehensive
      historical cohort study on Sardasht chemical victims' population which was
      designed to find out the long-term complications of sulfur mustard exposure and
      the basic mechanisms underlying clinical manifestations. This paper describes the
      design and methodology of Sardasht-Iran Cohort Study. METHODS: In Sardasht-Iran
      Cohort Study, 500 individuals including 372 subjects from Sardasht, as the
      exposed group, and 128 subjects from Rabat, as the unexposed age-matched control
      group were evaluated. The exposed group was divided into two groups based on the
      severity of clinical complications at the time of exposure. Different samples
      including blood, sputum, saliva, tear, urine, and semen were collected for
      immunologic, hematologic, biochemical, and other laboratory analysis. Data were
      gathered from medical records, clinical examinations, laboratory tests, and
      questionnaires for psychological and lifestyle situations. CONCLUSION: The
      important distinctions setting this study apart from the previous ones are
      discussed. The Sardasht-Iran Cohort Study provides important information on
      various aspects of long-term consequences of sulfur mustard exposure. This
      database will provide a better position to suggest guidelines for the diagnosis,
      treatment, and prevention of delayed complications in the patients exposed to
      sulfur mustard.

PMID- 19111024
TI  - Cancer incidence in Tehran metropolis: the first report from the Tehran
      Population-based Cancer Registry, 1998-2001.
AB  - BACKGROUND: There are no population-based data available for cancer in Tehran, a
      city that includes almost 10% of the Iranian population. This is the first report
      of cancer incidence in Tehran from a population-based cancer registry for the
      period of 1998-2001. METHODS: The cancer registry collects data on all new cases
      of cancer diagnosed in the resident population of Tehran metropolitan area. Data
      collection is active and trained abstractors visit close to 120 data sources
      comprising cancer diagnostic laboratories, secondary- and tertiary-care
      hospitals, and imaging centers to abstract cancer cases. RESULTS: During the
      period of 1998-2001, a total of 34,318 eligible cases were abstracted of which
      24% were identified just by death certificates. The overall age-standardized
      rates (ASR) (adjusted to the world population structure) were 163.0 per 100,000
      males and 141.8 per 100,000 females. The most frequently reported malignancies in
      males were stomach cancer (ASR 19.8), followed by cancers of the prostate (ASR
      15.6), lung (ASR 14.9), bladder (ASR 13.3), non-Hodgkin's lymphoma (ASR 7.1), and
      esophagus (ASR 6.8). In females, the most frequently reported malignancies were
      breast cancer (ASR 31.4), followed by cancers of the stomach (ASR 10.0), lung
      (ASR 7.0), ovary (ASR 6.8), and esophagus (ASR 5.3). CONCLUSION: The data
      reported by the Tehran Cancer Registry provide information on the cancer profile
      in Tehran metropolitan area. It clearly shows the breast and stomach, prostate,
      and tobacco-related cancers as major cancer in this population. The observed
      cancer rates indicate that Helicobacter pylori eradication, tobacco control
      measures, and early detection of breast cancer are of importance for cancer
      control in this population.

PMID- 19111025
TI  - The outcome of Iranian children on continuous ambulatory peritoneal dialysis: the
      first report of Iranian National Registry.
AB  - BACKGROUND: Continuous ambulatory peritoneal dialysis is not a very common
      modality to treat Iranian children with end-stage renal disease; however, there
      is sometimes no choice but to offer this therapy to salvage the patient.
      Obviously, promotion in each program needs re-evaluation to find the pitfalls.
      Therefore, a nation-wide survey on pediatric continuous ambulatory peritoneal
      dialysis was conducted to find the cause of death or termination of dialysis.
      METHODS: All children, younger than 14 years old, treated by continuous
      ambulatory peritoneal dialysis in nine main pediatric nephrology wards in Iran
      between 1993 and 2006 were included in this historical cohort study. Patient and
      technique survival rates were determined. Kaplan-Mayer and Cox-regression
      analysis were used to compare the survival. 2 x 2 table was used to calculate the
      risk ratio. A P<0.05 was considered significant. RESULTS: One hundred twenty
      children with a mean age of 47.6 months were on continuous ambulatory peritoneal
      dialysis. The most frequent cause of renal failure was hereditary-metabolic
      cystic disease. One hundred eighty-two peritoneal dialysis catheters were
      inserted surgically. The median first catheter exchange was 0.74 year (95%CI: 0.5
      - 0.98). The most frequent cause of catheter replacement was catheter outflow
      failure due to displacement, adhesion, and infection (persistent peritonitis or
      tunnel infection). The mean patient survival was 1.22 years (95%CI: 0.91 - 1.53).
      The mortality rate was 55% before 1997, and 60% between 1998 and 2001, which
      declined to 23% after 2002 (P<0.05). Young age (<24 months) was the only
      independent factor that predicted mortality (P<0.05). The outcome of children was
      as follows: recovery of renal function (6.7%), renal transplantation (8.3%),
      switch to hemodialysis (16.7%), still on continuous ambulatory peritoneal
      dialysis (23.3%), death (43.3%), and lost to follow-up (1.7%). CONCLUSION: The
      mortality is still high among Iranian children on peritoneal dialysis. Young age
      is the most important factor influencing on survival and mortality.

PMID- 19111026
TI  - Doppler waveform indices of fetal middle cerebral artery in normal 20 to 40 weeks
      pregnancies.
AB  - BACKGROUND: One of the main methods for evaluation of fetal well-being is
      analysis of Doppler flow velocity waveform of fetal vessels. Evaluation of
      Doppler wave of the middle cerebral artery can predict most of the at-risk
      fetuses in high-risk pregnancies. In this study, we tried to determine the normal
      ranges and their trends during pregnancy of Doppler flow velocity indices
      (resistive index, pulsatility index, systolic-to-diastolic ratio, and peak
      systolic velocity) of middle cerebral artery in 20 - 40 weeks normal pregnancies
      in Iranians. METHODS: In this cross-sectional study, 1037 women with normal
      pregnancy and gestational age of 20 to 40 weeks were investigated for fetal
      middle cerebral artery Doppler examination. RESULTS: Resistive index, pulsatility
      index, and systolic-to-diastolic ratio values of middle cerebral artery decreased
      in a parabolic pattern while the peak systolic velocity value increased linearly
      with progression of the gestational age. These changes were statistically
      significant (P<0.001 for all four variables) and were more characteristic during
      late weeks of pregnancy. The mean fetal heart rate was also significantly
      (P<0.001) reduced in correlation with the gestational age. CONCLUSION: Doppler
      waveform indices of fetal middle cerebral artery are useful means for determining
      fetal well-being. Herewith, the normal ranges of Doppler waveform indices for an
      Iranian population are presented.

PMID- 19111027
TI  - The effects of amniotic fluid on the histopathologic changes of exposed spinal
      cord in fetal sheep.
AB  - BACKGROUND: Experimental studies have shown that in myelomeningocele, the primary
      malformation is neural tissue damage resulting from exposure of neural tissue to
      amniotic fluid. In this study, the effects of amniotic fluid on histopathologic
      changes of exposed spinal cord in fetal sheep were evaluated. METHODS: In an
      experimental trial, 10 fetal sheep in two groups containing five subjects (group
      A) and five shams (group B) were studied. In the sheep at 90 - 100 days of
      gestation (term: 145 - 150 days) the lumbar skin was incised, paraspinal soft
      tissues were excised, laminectomy was performed at L2 - L4, and dura matter was
      opened. In group A, the dura matter was not dorsally closed and thus the spinal
      cord was left exposed to amniotic fluid, and in group B the skin was immediately
      closed. The lambs were delivered near term by cesarean section and were assessed
      clinically and morphologically. RESULTS: In group A, all lambs (n=5) had a
      complete or incomplete flaccid sensorimotor paraplegia and suffered from urine
      incontinence. Four lambs in this group were stool incontinent. In group B (n=4),
      only one lamb had paraparesis (P=0.048) and all lambs were urine and stool
      continent. In group A, all lambs had hypoplastic longitudinal muscles of the
      rectum but well- developed circular muscles. The anal sphincter muscles did not
      develop normally. In group B, all lambs had well-developed longitudinal and
      circular muscles and anal sphincter muscles developed normally (P=0.048).
      Histopathologic examination of the spinal cords showed edema, focal
      calcification, fibrosis, and capillary cell proliferation in group A, but in
      group B such changes were not seen. The number of ganglion cells was
      significantly higher in group B compared with group A (P<0.0005). CONCLUSION:
      Exposure of spinal cord to amniotic fluid causes structural neural tissue damage
      that can be prevented by fetal surgery through repairs of myelomeningocele.

PMID- 19111028
TI  - The Persian Bipolar Spectrum Diagnostic Scale and mood disorder questionnaire in
      screening the patients with bipolar disorder.
AB  - BACKGROUND: Considering the difficulties in diagnosing bipolar disorder in
      clinical practice and lack of needed screening instruments in Persian language,
      the present study aimed at assessing sensitivity, specificity, and predictive
      values for the Persian Bipolar Spectrum Diagnostic Scale. METHODS: The study was
      conducted in a university-affiliated hospital in Tehran, Iran, in a sample of 181
      consecutive outpatients aged 18-65 years. The used instruments were the
      Structured Clinical Interview for DSM-IV axis I disorders, the Persian Bipolar
      Spectrum Diagnostic Scale, the Persian Mood Disorder Questionnaire, and the Scale
      to Assess Unawareness of Mental Disorder. RESULTS: Most patients were males (58%)
      and had bipolar I disorder (57%). Other bipolar disorders and major depressive
      disorder were diagnosed as 5.5% and 21%, respectively. Test-retest of the Persian
      Bipolar Spectrum Diagnostic Scale and Mood Disorder Questionnaire demonstrated a
      good reliability for both. The sensitivity, specificity, and positive and
      negative predictive values of the Persian Bipolar Spectrum Diagnostic Scale at
      the score of 14, were 0.52, 0.79, 0.81, and 0.49, respectively. The sensitivity
      and specificity of the parallel application of the Persian Bipolar Spectrum
      Diagnostic Scale and Mood Disorder Questionnaire were 0.76 and 0.67,
      respectively. CONCLUSION: The Persian Bipolar Spectrum Diagnostic Scale and Mood
      Disorder Questionnaire are useful in screening patients with bipolar disorder in
      clinical psychiatric settings. Parallel use of both tests seems more effective
      than either alone.

PMID- 19111029
TI  - Infection control practices among dental professionals in Shiraz Dentistry
      School, Iran.
AB  - BACKGROUND: To assess the level of knowledge, attitude, and practice among
      Iranian dental healthcare professionals towards standard isolation precautions in
      Shiraz, Iran. METHODS: This study was a cross-sectional survey which was
      conducted on 152 Iranian dental professionals (faculty and students) from School
      of Dentistry, Shiraz University of Medical Sciences, Shiraz, Iran. A self
      administered questionnaire containing three parts (knowledge, attitude, and
      practice) was distributed to the participants. After validation of the survey,
      data were collected and analyzed. RESULTS: The survey was completed by 152
      (51.5%) of 295 potential respondents. The mean+/-SD scores of knowledge,
      attitude, and practice towards standard isolation precautions were 6.71+/-0.99,
      34.99+/-4.47, and 4.97+/-2.17 from the maximum scores of 9, 45, and 9,
      respectively. In addition, a positive linear correlation was found between the
      two items of the survey including knowledge-attitude (r= 0.394, P<0.001), and
      attitude and practice (r= 0.317, P<0.001). CONCLUSION: Practice of standard
      isolation precautions is poor among dental professionals in Shiraz University of
      Medical Sciences. This study showed that knowledge of infection control measures
      and a positive attitude towards them alone does not have an impact on adherence
      to recommendations.

PMID- 19111030
TI  - Division of the first dorsal compartment of the hand into two separated canals:
      rule or exception?
AB  - BACKGROUND: Tendon entrapment of the first dorsal compartment of the wrist, the
      de Quervain disease, is a common cause of wrist and hand pain and disability. A
      group of 50 consecutive patients operated for the treatment of de Quervain
      disease from 2003 through 2006 were prospectively studied to determine the
      variation in the pattern of the first extensor compartment. METHODS: Eighty-six
      percent of the patients were females, and 14% were males. In 80% of the cases the
      nondominant and in 20% the dominant hand was involved. These interesting findings
      may rule out the occupation's relation to de Quervain disease. RESULTS: Our study
      revealed that the compartment is completely separated into two canals in 86% of
      the patients which was significantly higher than that reported in similar
      studies. CONCLUSION: The existence of two separated compartments for abductor
      pollicis longus and extensor pollicis brevis tendons should be considered as a
      common finding during operation to prevent incomplete treatment and recurrence of
      the symptoms.

PMID- 19111031
TI  - Topical mitomycin-C for treatment of partially-excised ocular surface squamous
      neoplasia.
AB  - BACKGROUND: This study was conducted to determine the treatment outcome of
      incompletely removed, histopathologically documented ocular surface squamous
      neoplasia with mitomycin-C. METHODS: Through an interventional case series, 17
      eyes of 17 patients presented with incompletely removed ocular surface squamous
      neoplasia were treated according to a protocol using two to three alternate seven
      day courses of 0.04% mitomycin-C. Clinical recurrence was re-treated with the
      same protocol. All patients had weekly follow-up visits to the end of the
      treatment course, then biweekly visits for three months, and monthly visits,
      thereafter. RESULTS: The mean+/-SD follow-up period was 30.76+/-4.4 (range: 24.5 
      41) months. Five patients (29.4%) experienced recurrence after the initial
      treatment; four of them responded to retreatment and were disease-free till the
      end of follow-up. Survival analysis with Kaplan-Meier method was performed.
      Taking into account four recurrences, the 41-month nonrecurrence rate was 70.6%.
      However, including four of five patients with recurrence who responded to
      retreatment, the final outcome in survival analysis was 94.1% nonrecurrence for
      41 months of follow-up. All patients reported mild to moderate redness and
      irritation which were controlled with lubricants and mild corticosteroid eye
      drops. No serious ocular or systemic side effects were observed. CONCLUSION:
      Point zero four percent (0.04%) mitomycin-C drop used as two to three alternate
      seven-day courses seems to be a safe and effective treatment for ocular surface
      squamous neoplasia.

PMID- 19111032
TI  - The effectiveness of group positive parenting program on parental stress of
      mothers of children with attention-deficit/hyperactivity disorder.
AB  - BACKGROUND: The present study examined the influence of group positive parenting
      program on parental stress of mothers of children with attention
      deficient/hyperactivity disorder. Mothers of 13 children aged four to ten years,
      who met attention-deficient/hyperactivity disorder diagnosis by assessment of a
      child psychiatrist and clinical psychologist were selected from two child and
      adolescent psychiatric clinics of Tehran. To control the drug effects,
      researchers chose children who took methylphenidate (Ritalin) since six months
      before. METHODS: The group programs consisted of a six-weekly session of two
      hours duration, plus two telephone educational sessions, each one lasting 15
      minutes. Group was run by an experienced clinician who followed a specific
      training manual to ensure a standard format. These sessions continued with eight
      participants, because five of 13 mothers did not attend the classes. RESULTS: The
      results indicated that group positive parenting program caused mothers to
      experience lower stress. A two-month follow-up showed the stable efficiency of
      the program. CONCLUSION: This study revealed that the competency feeling and
      couples' harmony--as intervening variables--about nurturing the child were
      improved.

PMID- 19111033
TI  - Stem cell transplantation; Iranian experience.
AB  - From March 1991 through 31st December 2007, 2042 patients underwent stem cell
      transplantation at the Hematology-Oncology and Stem Cell Transplantation Research
      Center, affiliated to Tehran University of Medical Sciences. These
      transplantations included 1405 allogeneic stem cell transplantation, 624
      autologous stem cell transplantation, and 13 syngeneic stem cell transplantation.
      Stem cell transplantation was performed for various diseases including acute
      myelogenous leukemia, acute lymphoblastic leukemia, chronic myelogenous leukemia,
      chronic lymphoblastic leukemia, thalassemia major, sickle cell thalassemia,
      sickle cell disease, multiple myeloma, myelodysplasia, mucopolysaccharidosis,
      paroxysmal nocturnal hemoglobinuria, non-Hodgkin's lymphoma, Hodgkin's disease,
      severe aplastic anemia, plasma cell leukemia, Niemann-Pick disease, Fanconi
      anemia, severe combine immunodeficiency, congenital neutropenia, leukocyte
      adhesion deficiencies, Chediak-Higashi syndrome, osteopetrosis, histiocytosis X,
      Hurler syndrome, amyloidosis, systemic sclerosis, breast cancer, Ewing's sarcoma,
      testicular cancer, germ cell tumors, neuroblastoma, medulloblastoma, renal cell
      carcinoma, nasopharyngeal carcinoma, ovarian cancer, Wilms' tumor,
      rhabdomyosarcoma, pancreatoblastoma, and multiple sclerosis. We had 105 cellular
      therapies for postmyocardial infarction, multiple sclerosis, cirrhosis, head of
      femur necrosis, and renal cell carcinoma. About 30 patients were retransplanted
      in this center. About 74.9% of the patients (1530 of 2042) remained alive between
      one to 168 months after stem cell transplantation. Nearly 25.1% (512 of 2042) of
      our patients died after stem cell transplantation. The causes of deaths were
      relapse, infections, hemorrhagic cystitis, graft versus host disease, and others.

PMID- 19111034
TI  - Comparison of visual analogue scale and faces rating scale in measuring acute
      postoperative pain.
AB  - Several pain assessment tools have been proposed for use in different settings,
      but neither have been validated for all patients, especially Iranians. We
      conducted this study to compare the accuracy of two most commonly used tools for
      evaluation of pain intensity in a group of postoperative Iranian patients. All
      postoperative patients admitted to the surgical wards of Masih Daneshvari and
      Rasoul Akram Hospitals, Tehran, Iran were studied. During a two-month period,
      patients were evaluated for pain intensity within 24 hours of operation. Visual
      analogue scale and faces rating scale were used for this purpose. Eighty-two
      patients were enrolled into the study. Forty-eight patients underwent obstetrics
      and 34 had general surgeries. Using Spearman analysis, we found a linear
      correlation between the results of the two methods (P=0.952). Using multivariate
      analysis, we found that none of the variables such as age, gender, and education
      level had significant effects on correlation between visual analogue scale and
      faces rating scale. Visual analogue scale and faces rating scale are two pain
      assessment tools that can be used interchangeably for evaluation of acute
      postoperative pain.

PMID- 19111035
TI  - Autoimmune cholangiopathy with dacryocystitis.
AB  - Autoimmune liver diseases are different entities that sometimes have overlapping
      features. They share many of the general characteristics of autoimmune diseases,
      with systemic involvements. Here, we report a 30-year-old woman with ophthalmic
      symptoms of conjunctivitis and dacryocystitis who was treated completely. After a
      few months, the patient presented with autoimmune cholangiopathy. Sequelae of
      autoimmunity have been considered in different organs in this case.

PMID- 19111036
TI  - Scimitar syndrome.
AB  - Scimitar syndrome or congenital pulmonary venolobar syndrome is a rare anomaly
      most commonly consisting of partial pulmonary venous drainage into the hepatic
      portion of the inferior vena cava, right lung hypoplasia, dextroposition of the
      heart, and anomalous systemic arterial supply from aorta or one of its branches
      to the right lung. We report a four-year-old girl with recurrent pneumonia and
      failure to thrive, who was diagnosed as having scimitar syndrome.

PMID- 19111037
TI  - Photoclinic. Primary adenocarcinoma of the appendix presenting as a buttock mass.

PMID- 19111038
TI  - Photoclinic. Traumatic rupture of the thoracic aorta.

PMID- 19111039
TI  - Shiraz University School of Medicine: its foundation and development.
AB  - The history of Shiraz University School of Medicine (the former Pahlavi
      University School of Medicine) is important if we are to understand the
      development of medical education in Iran during the 20th century. This medical
      school took a unique path to its development including full-time faculty members,
      use of English as its institutional language, and emphasis on self learning.
      However, the most important of all is that it applied scientific method and
      modern knowledge to the problems of Iran and that it emphasized the importance of
      relevance of medical education to the problems of the region. This article
      summarizes the foundation and process of development of this school, emphasizing
      its unique features. This is not the history of individuals who were critical to
      its development. Nor a history of structures and buildings. Rather, it is the
      story of its intellectual development, and its process of change as the
      University became relevant.

PMID- 19111041
TI  - Tehran University of Medical Sciences--statement on publication ethics.

PMID- 19111040
TI  - Dr. Sir Muhammad Iqbal, Vermicelli, Vienna, and Ortner syndrome. A case report in
      correspondence.

PMID- 19111042
TI  - The message for World Kidney Day 2009: Hypertension and kidney disease: a
      marriage that should be prevented.

PMID- 19111043
TI  - Chemical and biological evaluations of an (111)in-labeled RGD-peptide targeting
      integrin alpha(V) beta(3) in a preclinical tumor model.
AB  - Angiogenesis plays a central role in tumor growth and metastasis. Quantification
      or evaluation of angiogenesis is crucial for antiangiogenic therapeutic
      strategies. Since integrin alpha(v)beta(3) overexpression appears specific of
      angiogenesis at the adult stage, it became a target of choice over the past
      decade, and labeled RGD-based compounds, therefore, constitute promising agents
      for noninvasive tumor visualization and targeting. We evaluated the chemical and
      biologic properties of a new tetrameric RGD-based tracer named RAFT-RGD. RAFT-RGD
      was radiolabeled with indium-111, using the chelating agent [(1,4,7,10
      tetraazacyclododecane-N,N',N'',N'''-tetraacetic acid] (DOTA). Labeling reaction
      parameters, such as time, temperature, solvent, or molar ratio, were investigated
      in order to optimize the final properties of the labeled RGD peptide. A 97.7% +/-
      0.7% binding efficiency was achieved. (111)In-DOTA-RAFT-RGD was injected
      intravenously in a cohort of alpha(v)beta(3)-positive tumor-bearing nude mice. We
      noninvasively visualized the in vivo distribution of the tracer, using a small
      animal gamma camera. In vivo distribution and stability were also studied after
      organ removal. In vivo, the radiolabeled peptide showed rapid blood clearance and
      tumor uptake. Whole-body noninvasive planar imaging allowed tumor visualization
      from 1 hour postinjection. However, renal uptake must be reduced to increase the
      therapeutic potential of RAFT-RGD.

PMID- 19111044
TI  - Knockdown of survivin and upregulation of p53 gene expression by small
      interfering RNA induces apoptosis in human gastric carcinoma cell line SGC-823.
AB  - BACKGROUND: The survivin gene may be a good target for cancer gene therapy
      because it is overexpressed in a variety of human tumors, including gastric
      cancer, but not in differentiated adult tissues. To explore effects of the siRNA
      of the survivin gene inducing apoptosis in human gastric cancer cells, three
      siRNAs, cpusiRNA1, cpusiRNA2, and cpusiRNA3, were designed and transferred into
      human gastric carcinoma cell line SGC-823 (SGC-823). MATERIALS AND METHODS: The
      opposite livability on SGC-823 cells was assayed with an MTT test. The change of
      mRNA and protein of survivin and p53 gene were detected by reverse-transcriptase
      polymerase chain reaction and Western blot, respectively. Cell apoptosis was
      assayed by flow cytometry. RESULTS: The growth of SGC-823 cells decreased by
      62.6%, 61.4%, and 55.1% when they were transfected with 400 nM of siRNA
      cpusiRNA1, cpusiRNA2, and cpusiRNA3 after 48 hours, in comparison to the control
      group. Also, the expression mRNA and protein of the survivin gene were knocked
      down, while the mRNA and protein of p53 gene were upregulated. SGC-823 cells
      presented an increase in apoptosis index. CONCLUSIONS: Small interfering RNA can
      exert a knockdown of the survivin gene expression and upregulation the p53 gene
      in SGC-823 cells and effectively induce apoptosis and inhibit the growth of human
      gastric carcinoma cell line SGC-823.

PMID- 19111045
TI  - Comparative dosimetric evaluation of nanotargeted (188)Re-(DXR)-liposome for
      internal radiotherapy.
AB  - A dosimetric analysis was performed to evaluate nanoliposomes as carriers of
      radionuclides ((188)Re-liposomes) and radiochemotherapeutic drugs [(188)Re
      doxorubicin (DXR)-liposomes] in internal radiotherapy for colon carcinoma, as
      evaluated in mice. METHODS: Pharmacokinetic data for (188)Re-N, N-bis (2
      mercaptoethyl)-N',N'-diethylethylenediamine (BMEDA), (188)Re-liposome, and
      (188)Re-DXR-liposome were obtained for the estimation of absorbed doses in tumors
      and normal organs. Two colon carcinoma mouse models were employed: subcutaneous
      growing solid tumor and malignant ascites pervading tumor models. Radiation-dose
      estimates for normal tissues and tumors were calculated by using the OLINDA/EXM
      program. An evaluation of a recommended maximum administered activity (MAA) for
      the nanotargeted drugs was also made. RESULTS: Mean absorbed doses derived from
      (188)Re-liposome and (188)Re-DXR-liposome in normal tissues were generally
      similar to those from (188)Re-BMEDA in intraperitoneal and intravenous
      administration. Tissue-absorbed dose in the liver was 0.24-0.40 and 0.17-0.26
      (mGy/MBq) and in red marrow was 0.033-0.050 and 0.038-0.046 (mGy/MBq),
      respectively, for (188)Re-liposome and (188)Re-DXR-liposome. Tumor-absorbed doses
      for the nanotargeted (188)Re-liposome and (188)Re-DXR-liposome were higher than
      those of (188)Re-BMEDA for both routes of administration (4-26-fold). Dose to red
      marrow defined the recommended MAA. CONCLUSIONS: Our results suggest that
      radionuclide and chemoradiotherapeutic passive targeting delivery, using
      nanoliposomes as the carrier, is feasible and promising in systemic-targeted
      radionuclide therapy.

PMID- 19111046
TI  - Imaging of therapy-induced apoptosis using (99m)Tc-HYNIC-annexin V in thymoma
      tumor-bearing mice.
AB  - The primary focus of this study was to assess the potential of (99m)Tc-HYNIC
      Annexin V for in vivo imaging of apoptosis after systemic chemotherapy and "more
      localized" radiotherapy in nude mice bearing thymoma tumors and correlating it
      with TUNEL staining. (99m)Tc-HYNIC-Annexin V was administered intravenously to
      tumor-bearing mice (n = 25) before and after therapy. Mice were then imaged at 4
      hours postinjection, and the animals were subsequently sacrificed. Tumor uptake
      increased significantly in response to treatment [chemotherapy (n = 8): 1.80 +/-
      0.52 %ID/g, p < 0.009; radiotherapy (n = 7): 0.81 +/- 0.07 %ID/g, p < 0.02],
      compared to the control group (n = 10) (0.57 +/- 0.05 %ID/g). Tumor-to-muscle
      (T:M) and tumor-to-blood (T:B) ratios were significantly higher in both
      chemotherapy-treated (p < 0.02 and p < 0.01) and radiotherapy-treated cohorts (p
      < 0.05 and p < 0.03), compared to the control cohorts at 4 hours postinjection of
      (99m)Tc-Annxin V. In the post-therapy cohorts, the immunohistochemistry studies
      indicated a statistically significant correlation between tumor uptake of (99m)Tc
      HYNIC-Annexin V and the extent of apoptosis detected by TUNEL-positive staining
      (r(2) = 0.41). The physiologic localization of the agent was found mainly in the
      kidneys (34%), liver (11%), and urine (22%). The results suggest that (99m)Tc
      HYNIC-Annexin V may be an ideal agent for imaging apoptosis in response to
      treatment in a thymoma tumor bearing mouse model.

PMID- 19111047
TI  - Biodistribution and dosimetry of (131)I in thyroidectomy patients using
      semiquantitative gamma-camera imaging.
AB  - The aim of this study was to determine the biodistribution, effective retention
      half-time (T(eff)), and internal organ dosimetry of (131)I administered to
      patients with papillary thyroid cancer after a total or near total thyroidectomy,
      and whole-body and organ activity was measured by gamma-camera imaging at 16 time
      points over 5 days following the administration of 1.1 GBq of (131)I in 5
      patients. Whole-body scanning was performed by using a Siemens E-CAM() gamma
      camera at a fixed distance of 5 cm from the patient. (131)I activity in regions
      of interest (ROIs) corresponding to the bladder, heart wall, kidneys, liver,
      lower gastrointestinal tract, lung, stomach, and thyroid remnants were measured,
      with measurements in the thigh used as the background. Most activity was
      localized to the lower gastrointestinal tract and thyroid remnants on day 1. The
      longest T(eff) was in the lung and the shortest was in the bladder (34.0 and 16.8
      hours, respectively). The three organs with the highest absorbed doses per unit
      of administered activity were the lower gastrointestinal tract (2.03 mSv/MBq),
      the stomach (1.32 mSv/MBq), and the heart wall (1.24 mSv/MBq). T(eff) for thyroid
      remnants and the whole body were also estimated. We evaluated these organ doses
      to determine the normal tissues most likely at risk for stochastic and
      deterministic effects associated with (131)I therapy for thyroid cancer and
      benign disease. Our results represent preliminary findings, and the study will
      continue to accrue a greater number of study participants.

PMID- 19111048
TI  - Review: update on selection of optimal radiopharmaceuticals for clinical trials.
AB  - Multiple formulations of radiopharmaceuticals (RPs) are possible because of
      engineering at the nanometer scale. Yet, numbers of patients are limited, and the
      cost of each clinical trial is high. Thus, there is the need of preclinical
      evaluation of one agent versus another for the selection of an optimal choice. In
      the application of RPs to cancer, this selection involves both visualization and
      treatment aspects. In this paper, we propose the use of imaging and therapeutic
      figures of merit (IFOM and TFOM, respectively) to select the optimal structure
      and radiolabel for subsequent clinical trials given animal biodistribution
      results. Limiting cases and Monte Carlo simulation were used to demonstrate that
      these modern figures of merit are superior to traditional ratio functions that
      have been employed in these two contexts. Finally, there is the question of how
      animal and human results resemble each other kinetically. We considered allometry
      and compared mouse and human results for several of the cognate cT84.66
      antibodies (anti-CEA; carcinoembryonic antigen). While kinetics of intact and 120
      kDa engineered proteins are similar across the two species, the 80-kDa cognate
      shows a manifest difference in the RP first moment in the blood. In particular,
      human blood clearance is slower than that seen in the nude mouse. We suggest that
      such allometric comparisons become standard in the reporting of clinical trials.

PMID- 19111049
TI  - Preparation and in-vivo evaluation of (188)Re(CO)(3)-colchicine complex for use
      as tumor-targeting agent.
AB  - The Re(I)-tricarbonyl synthon, [(188)Re(H(2)O)(3)(CO)(3)](+), was prepared by
      using carbon monoxide gas and amine-borane as the reducing agent. Colchicine, a
      naturally occurring cytotoxic alkaloid, was derivatized to iminodiacetic acid,
      the required array for the tridentate ligand system for coordination to the Re(I)
      tricarbonyl core. (188)Re(CO)(3)-colchicine iminodiacetic acid (IDA) complex
      could be prepared in >95% radiochemical purity, as determined by high-performance
      liquid chromatography. The chemical characterization of (188)Re(CO)(3)-colchicine
      IDA complex has been carried out by preparing the corresponding cold Re(CO)(3)
      complex. The radiolabeled complex was stable at room temperature, even after 48
      hours postpreparation, as well as against histidine and cysteine ligand exchange
      studies. Biodistribution studies were carried out in the murine fibrosarcoma
      tumor model. Tumor uptake of 1.7 +/- 0.03 percent injected dose per g (%ID/g) was
      observed at 3 hours postinjection (h.p.i.), which increased to 4.1 +/- 1.3 %ID/g
      at 24 h.p.i. Tumor-blood and tumor-muscle ratios were 0.14 and 1 at 1 h.p.i. that
      increased to 0.95 and 4 at 24 h.p.i., respectively. Retention of the complex in
      tumor for more than one half-life of (188)Re(t(1/2) = 17 hours) indicates its
      potentiality for tumor therapy.

PMID- 19111050
TI  - Diversification of existing reference phantoms in nuclear medicine: Calculation
      of specific absorbed fractions for 21 mathematical phantoms and validation
      through dose estimates resulting from the administration of (18)F-FDG.
AB  - Current dose assessment in nuclear medicine patient studies relies on published S
      values, which are, in turn, based on calculated specific absorbed fractions
      (SAFs) available for a limited number of anthro-pomorphic computational phantoms.
      In order to take the individual physiognomy of patients more into account, this
      study aimed to broaden the supply of phantoms and their respective SAFs. An
      ensemble of 21 mathematical phantoms was submitted to the Monte Carlo Code
      MCNP4c2 for the purpose of calculation of SAFs for annihilation radiation. These
      values were incorporated into an internal dose assessment following the Medical
      Internal Radiation Dose (MIRD) schema and relying on published biokinetic data
      for intravenous administration of (18)F-FDG. The results were compared with data
      from the ICRP, MIRD reports and concurrent calculations with OLINDA/EXM. A very
      good agreement with sources relying on the SAFs of Cristy and Eckerman (i.e., the
      ICRP and OLINDA/EXM) was observed, with the absorbed dose in lung being the only
      exception. In the case of dose to red marrow, the King Spiers factors were
      omitted in the three-factor approximation, which led to a precise accordance with
      the Cristy/Eckerman values. Summarizing, one can say that the coincidence with
      published data justifies the method chosen and demonstrates successfully the
      expansion of available reference phantoms for dose assessment in nuclear
      medicine.

PMID- 19111051
TI  - Development of a spherical (125)i-brachytherapy seed for its application in the
      treatment of eye and prostate cancer.
AB  - Palladium-coated silver beads of 0.5 mm (phi) were used to adsorb (125)I,
      encapsulated inside a titanium capsule by an Nd:YAG laser, for use as a
      brachytherapy source. Experimental conditions, such as feed activity, carrier
      concentration, and reaction time, were optimized for the maximum adsorption of
      (125)I. Uniform distribution of radioactivity on the source core was ascertained
      by the autoradiography technique. Leachability of (125)I was found to be <0.01%.
      The dose-rate constant of the new source was estimated to be 1.045 cGyh(-1)U(-1).
      This newly developed source could be an alternative to other (125)I sources.

PMID- 19111052
TI  - Short Communication: (18)F-immuno-PET: Determination of anti-CD66 biodistribution
      in a patient with high-risk leukemia.
AB  - The monoclonal antibody anti-CD66 labeled with (99m)Tc is widely used as
      Scintimun granulocyte for bone marrow immunoscintigraphy. Further, recently
      performed clinical radioimmunotherapy studies with [(90)Y]Y-anti-CD66 proved to
      be suitable for the treatment of hematologic malignancies. Before
      radioimmunotherapy with [(90)Y]Y-anti-CD66, dosimetric estimations are required
      to minimize radiotoxicity and determine individual applicable activities. Planar
      imaging, using gamma-emitting radionuclides, is conventionally carried out to
      estimate the absorbed organ doses. In contrast, immuno-PET (positron emission
      tomography) enables the quantification of anti-CD66 accumulation and provides
      better spatial and temporal resolution. Therefore, in this study, a semiautomated
      radiosynthesis of [(18)F]F-anti-CD66 was developed, using the (18)F-acylation
      agent, N-succinimidyl-4-[(18)F]fluorobenzoate ([(18)F]SFB). As a proof of
      concept, an intraindividual comparison between PET and conventional scintigraphy,
      using (18)F- and (99m)Tc-labeled anti-CD66 in 1 patient with high-risk leukemia,
      is presented. Both labeled antibodies displayed a similar distribution pattern
      with high preferential uptake in bone marrow. Urinary excretion of [(18)F]F-anti
      CD66 was increased and bone marrow uptake reduced, in comparison to [(99m)Tc]Tc
      anti-CD66. Nevertheless, PET-based dosimetry with [(18)F]F-anti-CD66 could
      provide additional information to support conventional scintigraphy. Moreover,
      [(18)F]F-anti-CD66 is ideally suited for bone marrow imaging using PET.

PMID- 19111053
TI  - (18)F-FDG PET in Pediatric Lymphomas: A Comparison with Conventional Imaging.
AB  - This study reports on our experience with 18F-fluorodeoxyglucose (FDG) positron
      emission tomography (PET) in pediatric patients affected by Hodgkin's disease
      (HD) and non-Hodgkin's lymphoma (NHL). We studied 20 pediatric subjects (12
      males, 8 females; mean age, 10 years; range, 6 months to 14 years) with malignant
      lymphoma (9 HD, 11 NHL) for a 4-year period of time. Overall, 45 PET scans were
      performed: 7 at disease presentation and 38 for evaluation of response to therapy
      or follow-up study. All PET results were compared with conventional imaging (CI),
      mainly computed tomography (CT) and/or magnetic resonance imaging (MRI), and
      supported by clinical follow-up and/or histologic data. In 18 of 20 patients, PET
      findings correctly identified the status of disease. Two (2) subjects
      (respectively, 1 HD and 1 NHL, both at follow-up) resulted falsely positive: 1
      due to prominent thymic uptake, and the other due to nonspecific inflammation. Of
      45 scans, PET findings were consistent with clinical follow-up and other CI data
      in 43 cases (16 true-positive and 27 true-negative results) and resulted falsely
      positive in the remaining 2 scans. On a lesion-by-lesion basis (overall, 153
      lesions: 84 nodal and 69 extranodal), we found a concordance between CI and PET
      findings in 25 nodal (29.8%) and in 22 extranodal sites (32%). PET was more
      accurate than CI, as it identified active disease in 1 patient negative at CI and
      excluded relapse in 6 patients with inconclusive CI and in 2 patients with a
      falsely positive CI. Overall, PET sensitivity and specificity was 100% and 93%
      versus 94% sensitivity and 72.4% specificity for CI. This comparative study shows
      FDG PET to be more accurate than CI in evaluating children with lymphoma. Our
      data also confirms that (18)F-FDG PET may show false-positive findings.

PMID- 19111054
TI  - A series of halogenated heterodimeric inhibitors of prostate specific membrane
      antigen (PSMA) as radiolabeled probes for targeting prostate cancer.
AB  - Prostate specific membrane antigen (PSMA) is a validated molecular marker for
      prostate cancer. A series of glutamate-urea (Glu-urea-X) heterodimeric inhibitors
      of PSMA were designed and synthesized where X = epsilon-N-(o-I, m-I, p-I, p-Br, o
      Cl, m-Cl, p-Cl, p-F, H)-benzyl-Lys and epsilon-(p-I, p-Br, p-Cl, p-F, H)
      phenylureido-Lys. The affinities for PSMA were determined by screening in a
      competitive binding assay. PSMA binding of the benzyllysine series was
      significantly affected by the nature of the halogen substituent (IC(50) values,
      Cl < I = Br << F = H) and the ring position of the halogen atom (IC(50) values, p
      I < o-I << m-I). The halogen atom had little affect on the binding affinity in
      the para substituted phenylureido-Lys series. Two lead iodine compounds were
      radiolabeled with (123)I and (131)I and demonstrated specific PSMA binding on
      human prostate cancer cells, warranting evaluation as radioligands for the
      detection, staging, and monitoring of prostate cancer.

PMID- 19111056
TI  - Identification of temporal differentially expressed protein responses to
      microcystin in human amniotic epithelial cells.
AB  - The increased distribution of microcystins (MCs) has become a global issue.
      However, the MC response machinery has not been completely studied and elucidated
      until now. Our previous dose-related analysis has revealed that different
      concentrations of mirocystin-RR (MC-RR) can trigger comprehensive and various
      alterations in the protein expression profile using a proteomic approach. To
      further dissect the kinetics of cellular responses associated with MC-RR
      cytotoxic effects, the present study has set out to investigate the temporal
      protein expression pattern at three time points (3, 12, and 24 h after exposure).
      The relative intensity has changed significantly in MC-RR-treated FL cells, as
      compared with the control, in a total of 127 protein spots. One hundred and two
      proteins have been further identified with high confidence by peptide mass
      fingerprinting. These proteins can be categorized into diverse functional classes
      such as signal transduction, apoptosis, protein degradation, cell cycle, cell
      differentiation, transporter, and so forth. The wide range of different proteins
      involved suggests that MC-RR has profound effects on the biological response and
      toxic consequences of the affected cells. The identification of p53 and its
      potential targets confirms a known role for p53 in the MC-RR response. Moreover,
      it is noteworthy that MC-RR can up-regulate the expression of the PP2A A subunit
      and down-regulate the expression of a number of proteins implicated in the
      ubiquitin-proteasome pathway. Therefore, the present expression data provide a
      global view of dynamic changes in cell responses to MC-RR and, more importantly,
      generate novel hypotheses regarding MC-RR-responsive mechanisms.

PMID- 19111055
TI  - Innovative application of fluoro tagging to trace airborne particulate and gas
      phase polybrominated diphenyl ether exposures.
AB  - Polybrominated diphenyl ethers (PBDEs) are flame retardants applied as coatings
      to many consumer products, including household items. PBDEs are released and
      produce airborne vapors and dusts. Inhalation of particle-phase and/or gas-phase
      PBDEs is therefore a major route of exposure. In an attempt to mimic realistic
      airborne exposures, actual uptake, and deposition of particles and vapors, we
      prepared and characterized particles for future animal exposure studies. To trace
      the particles in environmental and biological systems, we employed fluoro
      tagging. We synthesized, characterized, and employed three PBDE congeners, 35,
      47, and 99, and five fluoro-substituted PBDEs (F-PBDEs), 17-F5' 25-F5', 28-F3',
      35-F5', 47-F3, and 99-F3', for this study. The PBDE congeners were selected
      because they are commonly found in house dust. For that reason, we coated
      spherical silica particles of 3 microm and C18 endcapped silica as representative
      and inert support materials, with 20, 30, and 40% PBDEs. We determined the
      particle size distributions by aerodynamic particle size spectrometry and the
      morphology by scanning electron microscopy. The suitability of the fluoro-tagged
      tracers to mimic their corresponding parent PBDEs was investigated by extraction
      studies from spiked blood serum. Our study is of fundamental importance to the
      development of xenobiotic tracers for monitoring routes of human exposure to
      PBDEs and understanding uptake of PBDEs from particles and vapors.

PMID- 19111057
TI  - Regioselective synthesis of tetrasubstituted pyrroles by 1,3-dipolar
      cycloaddition and spontaneous decarboxylation.
AB  - We developed a novel regioselective synthesis of tetrasubstituted pyrroles via
      the classic 1,3-dipolar cycloaddition of alpha,beta-unsaturated benzofuran-3(2H)
      one and azlactones (1) followed by spontaneous decarboxylation. The complete
      regiochemical control of tetrasubstituted pyrroles was confirmed by the
      orthogonal synthesis of complementary regioisomers (7a and 7b) simply by using
      different azlactones (1a and 1b, respectively).

PMID- 19111059
TI  - Convergent formal syntheses of (+/-)-brussonol and (+/-)-abrotanone via an
      intramolecular Marson-type cyclization.
AB  - The formal convergent syntheses of both (+/-)-brussonol and (+/-)-abrotanone are
      reported. The key step involved the diastereoselective capture of an in situ
      generated oxocarbenium cation via an intramolecular Friedel-Crafts/Marson-type
      cyclization.

PMID- 19111058
TI  - Nucleophilic addition of organozinc reagents to 2-sulfonyl cyclic ethers:
      stereoselective synthesis of manassantins A and B.
AB  - A convergent route to the synthesis of manassantins A and B, potent inhibitors of
      HIF-1, is described. Central to the synthesis is a stereoselective addition of an
      organozinc reagent to a 2-benzenesulfonyl cyclic ether to achieve the 2,3-cis-3,4
      trans-4,5-cis-tetrahydrofuran of the natural products. Preliminary structure
      activity relationships suggested that the (R)-configuration at C-7 and C-7''' is
      not critical for HIF-1 inhibition. In addition, the hydroxyl group at C-7 and C
      7''' can be replaced with a carbonyl group without loss of activity.

PMID- 19111060
TI  - Broadly applicable synthesis of 1,2,4,5-tetraoxanes.
AB  - Re(2)O(7) is a mild and efficient catalyst for the high-yielding condensation of
      1,1-dihydroperoxides with ketones or aldehydes to form 1,2,4,5-tetraoxanes,
      including targets not easily prepared via existing methodology. When applied in
      tandem with a recently reported Re(VII)-catalyzed synthesis of 1,1
      dihydroperoxides, the reaction provides a high-yielding one-pot conversion of
      ketones or aldehydes to tetraoxanes.

PMID- 19111063
TI  - Construction of a three-dimensional polynuclear zinc compound based on unique
      metallophthalocyanine-like subunits.
AB  - A polynuclear zinc compound, [Zn(7)(BTA)(7)(OABDC)(mu(3)-OH)(2)(mu(2)
      OH)(2).H(2)O] (1), has been prepared by using benzotriazole (HBTA) and 5
      oxyacetatoisophthalic acid (H(3)OABDC) as ligands under hydrothermal conditions.
      For compound 1, an unprecedented metallophthalocyanine-like "Zn(2)(mu(3)-OH)(2)
      subset [Zn(4)BTA(4)]" subunit is constructed from eta(3)-BTA ligands and Zn atoms
      and further linked via mu(2)-OH, outer four-connected Zn atoms, and 5
      oxyacetateisophthalic acid to form a novel three-dimensional framework.

PMID- 19111064
TI  - Strong coordination of tetraphenylborate anion to copper(I) bipyridine and
      phenanthroline-based complexes and its effect on catalytic activity in the
      cyclopropanation of styrene.
AB  - The synthesis, characterization, and cyclopropanation activity of tetrahedral
      copper(I) complexes with bipyridine- and phenanthroline-based ligands containing
      strongly coordinated tetraphenylborate anions are reported. Cu(I)(bpy)(BPh(4)),
      Cu(I)(phen)(BPh(4)), and Cu(I)(3,4,7,8-Me(4)phen)(BPh(4)) complexes are the first
      examples in which the BPh(4)(-) counterion chelates a transition metal center in
      bidentate fashion through eta(2) pi interactions with two of its phenyl rings.

PMID- 19111065
TI  - Stereoselective hydrogenation of aromatic alkynes using water, triethylsilane, or
      methanol, mediated and catalyzed by Ni(0) complexes.
AB  - The use of complexes of the type [(P-P)Ni(eta(2)-C,C-alkyne)] (P-P = 1,2-bis(di
      isopropyl-phosphinoethane or 1,2-bis(diterbutylphosphino-ethane) in the presence
      of water, triethylsilane/water, or methanol as hydrogen sources yields the
      selective production of E- or Z- aromatic alkenes from the corresponding alkynes.
      For instance, in the case of diphenylacetylene (dpa) and water, a metal-mediated
      process was found to yield trans-stilbene stoichiometrically, whereas in the case
      of triethylsilane/water and methanol, a catalytic system (1% mol) was found. The
      catalytic systems gave >95% conversion to cis- or trans-stilbene, respectively.
      The use of a variety of substituents on the aromatic ring was also assessed.
      Deuterium-labeling studies using D(2)O allowed the confirmation of water as the
      hydrogen source for the alkyne reduction.

PMID- 19111062
TI  - From solvolysis to self-assembly.
AB  - My sojourn from classical physical-organic chemistry and solvolysis to self
      assembly and supramolecular chemistry, over the last forty years, is described.
      My contributions to unsaturated reactive intermediates, namely vinyl cations and
      unsaturated carbenes, along with my decade-long involvement with polyvalent
      iodine chemistry, especially alkynyliodonium salts, as well as my more recent
      research with metal-ligand, coordination driven, and directed self-assembly of
      finite supramolecular ensembles are discussed.

PMID- 19111066
TI  - Lack of association between PKLR rs3020781 and NOS1AP rs7538490 and type 2
      diabetes, overweight, obesity and related metabolic phenotypes in a Danish large
      scale study: case-control studies and analyses of quantitative traits.
AB  - BACKGROUND: Several studies in multiple ethnicities have reported linkage to type
      2 diabetes on chromosome 1q21-25. Both PKLR encoding the liver pyruvate kinase
      and NOS1AP encoding the nitric oxide synthase 1 (neuronal) adaptor protein
      (CAPON) are positioned within this chromosomal region and are thus positional
      candidates for the observed linkage peak. The C-allele of PKLR rs3020781 and the
      T-allele of NOS1AP rs7538490 are reported to strongly associate with type 2
      diabetes in various European-descent populations comprising a total of 2,198
      individuals with a combined odds ratio (OR) of 1.33 [1.16-1.54] and 1.53 [1.28
      1.81], respectively. Our aim was to validate these findings by investigating the
      impact of the two variants on type 2 diabetes and related quantitative metabolic
      phenotypes in a large study sample of Danes. Further, we intended to expand the
      analyses by examining the effect of the variants in relation to overweight and
      obesity. METHODS: PKLR rs3020781 and NOS1AP rs7538490 were genotyped, using
      TaqMan allelic discrimination, in a combined study sample comprising a total of
      16,801 and 16,913 individuals, respectively. The participants were ascertained
      from four different study groups; the population-based Inter99 cohort (nPKLR =
      5,962, nNOS1AP = 6,008), a type 2 diabetic patient group (nPKLR = 1,873, nNOS1AP
      = 1,874) from Steno Diabetes Center, a population-based study sample (nPKLR =
      599, nNOS1AP = 596) from Steno Diabetes Center and the ADDITION Denmark screening
      study cohort (nPKLR = 8,367, nNOS1AP = 8,435). RESULTS: In case-control studies
      we evaluated the potential association between rs3020781 and rs7538490 and type 2
      diabetes and obesity. No significant associations were observed for type 2
      diabetes (rs3020781: pAF = 0.49, OR = 1.02 [0.96-1.10]; rs7538490: pAF = 0.84, OR
      = 0.99 [0.93-1.06]). Neither did we show association with overweight or obesity.
      Additionally, the PKLR and the NOS1AP genotypes were demonstrated not to have a
      major influence on diabetes-related quantitative metabolic phenotypes.
      CONCLUSION: We failed to provide evidence of an association between PKLR
      rs3020781 and NOS1AP rs7538490 and type 2 diabetes, overweight, obesity or
      related quantitative metabolic phenotypes in large-scale studies of Danes.

PMID- 19111067
TI  - Analysis on conservation of disulphide bonds and their structural features in
      homologous protein domain families.
AB  - BACKGROUND: Disulphide bridges are well known to play key roles in stability,
      folding and functions of proteins. Introduction or deletion of disulphides by
      site-directed mutagenesis have produced varying effects on stability and folding
      depending upon the protein and location of disulphide in the 3-D structure. Given
      the lack of complete understanding it is worthwhile to learn from an analysis of
      extent of conservation of disulphides in homologous proteins. We have also
      addressed the question of what structural interactions replaces a disulphide in a
      homologue in another homologue. RESULTS: Using a dataset involving 34,752
      pairwise comparisons of homologous protein domains corresponding to 300 protein
      domain families of known 3-D structures, we provide a comprehensive analysis of
      extent of conservation of disulphide bridges and their structural features. We
      report that only 54% of all the disulphide bonds compared between the homologous
      pairs are conserved, even if, a small fraction of the non-conserved disulphides
      do include cytoplasmic proteins. Also, only about one fourth of the distinct
      disulphides are conserved in all the members in protein families. We note that
      while conservation of disulphide is common in many families, disulphide bond
      mutations are quite prevalent. Interestingly, we note that there is no clear
      relationship between sequence identity between two homologous proteins and
      disulphide bond conservation. Our analysis on structural features at the sites
      where cysteines forming disulphide in one homologue are replaced by non-Cys
      residues show that the elimination of a disulphide in a homologue need not always
      result in stabilizing interactions between equivalent residues. CONCLUSION: We
      observe that in the homologous proteins, disulphide bonds are conserved only to a
      modest extent. Very interestingly, we note that extent of conservation of
      disulphide in homologous proteins is unrelated to the overall sequence identity
      between homologues. The non-conserved disulphides are often associated with
      variable structural features that were recruited to be associated with
      differentiation or specialisation of protein function.

PMID- 19111068
TI  - Ethnopharmacological survey of six medicinal plants from Mali, West-Africa.
AB  - An ethnopharmacological survey was carried out to collect information about the
      use of six medicinal plants in the regions around Siby and Dioila, Mali. The
      plants investigated were Biopyhtum petersianum, Cola cordifolia, Combretum molle,
      Opilia celtidifolia, Parkia biglobosa and Ximenia americana. More than 60 medical
      indications were reported for the use of these plants in traditional medicine.
      The most frequently reported ailments were malaria (25.6%), different types of
      pain (14.0%) and dermatitis (7.4%). The main forms for preparation were decoction
      (58.1%) and powdered plant material (28.4%). The most frequent used plant parts
      were leaves (37.7%) and stem bark (18.6%). The healers' consensus for the main
      indications is fairly high for the four plants B. petersianum, C. cordifolia, C.
      molle and O. celtidifolia, and this supports the traditional use of these plants.
      However for P. biglobosa and X. americana the healers' consensus is less
      consistent and it is more difficult to draw conclusions about the most important
      traditional use of these two plants.

PMID- 19111069
TI  - Transcriptional regulation of BRD7 expression by Sp1 and c-Myc.
AB  - BACKGROUND: Bromodomain is an evolutionally conserved domain that is found in
      proteins strongly implicated in signal-dependent transcriptional regulation.
      Genetic alterations of bromodomain genes contributed to the development of many
      human cancers and other disorders. BRD7 is a recently identified bromodomain
      gene. It plays a critical role in cellular growth, cell cycle progression, and
      signal-dependent gene expression. Previous studies showed that BRD7 gene
      exhibited much higher-level of mRNA expression in normal nasopharyngeal epithelia
      than in nasopharyngeal carcinoma (NPC) biopsies and cell lines. However, little
      is known about its transcriptional regulation. In this study, we explored the
      transcriptional regulation of BRD7 gene. METHOD: Potential binding sites of
      transcription factors within the promoter region of BRD7 gene were predicted with
      MatInspector Professional http://genomatix.de/cgi
      bin/matinspector_prof/mat_fam.pl. Mutation construct methods and luciferase
      assays were performed to define the minimal promoter of BRD7 gene. RT-PCR and
      western blot assays were used to detect the endogenous expression of
      transcription factor Sp1, c-Myc and E2F6 in all cell lines used in this study.
      Electrophoretic mobility shift assays (EMSA) and Chromatin immunoprecipitation
      (ChIP) were used to detect the direct transcription factors that are responsible
      for the promoter activity of BRD7 gene. DNA vector-based siRNA technology and
      cell transfection methods were employed to establish clone pools that stably
      expresses SiRNA against c-Myc expression in nasopharyngeal carcinoma 5-8F cells.
      Real-time PCR was used to detect mRNA expression of BRD7 gene in 5-8F/Si-c-Myc
      cells. RESULTS: We defined the minimal promoter of BRD7 gene in a 55-bp region
      (from -266 to -212bp), and identified that its promoter activity is inversely
      related to c-Myc expression. Sp1 binds to the Sp1/Myc-Max overlapping site of
      BRD7 minimal promoter, and slightly positively regulate its promoter activity. c
      Myc binds to this Sp1/Myc-Max overlapping site as well, and negatively regulates
      the promoter activity and endogenous mRNA expression of BRD7 gene. Knock-down of
      c-Myc increases the promoter activity and mRNA level of BRD7 gene. The luciferase
      activity of the mutated promoter constructs showed that Sp1/Myc-Max overlapping
      site is a positive regulation element of BRD7 promoter. CONCLUSION: These studies
      provide for the first time the evidence that c-Myc is indeed a negative regulator
      of BRD7 gene. These findings will help to further understand and uncover the bio
      functions of BRD7 gene involved in the pathogenesis of NPC.

PMID- 19111070
TI  - Differential selection on gene translation efficiency between the filamentous
      fungus Ashbya gossypii and yeasts.
AB  - BACKGROUND: The filamentous fungus Ashbya gossypii grows into a multicellular
      mycelium that is distinct from the unicellular morphology of its closely related
      yeast species. It has been proposed that genes important for cell cycle
      regulation play central roles for such phenotypic differences. Because A.
      gossypii shares an almost identical set of cell cycle genes with the typical
      yeast Saccharomyces cerevisiae, the differences might occur at the level of
      orthologous gene regulation. Codon usage patterns were compared to identify
      orthologous genes with different gene regulation between A. gossypii and nine
      closely related yeast species. RESULTS: Here we identified 3,151 orthologous
      genes between A. gossypii and nine yeast species. Two groups of genes with
      significant differences in codon usage (gene translation efficiency) were
      identified between A. gossypii and yeasts. 333 genes (Group I) and 552 genes
      (Group II) have significantly higher translation efficiency in A. gossypii and
      yeasts, respectively. Functional enrichment and pathway analysis show that Group
      I genes are significantly enriched with cell cycle functions whereas Group II
      genes are biased toward metabolic functions. CONCLUSION: Because translation
      efficiency of a gene is closely related to its functional importance, the
      observed functional distributions of orthologous genes with different translation
      efficiency might account for phenotypic differentiation between A. gossypii and
      yeast species. The results shed light on the mechanisms for pseudohyphal growth
      in pathogenic yeast species.

PMID- 19111072
TI  - Localized renal cell carcinoma management: an update.
AB  - OBJECTIVE: To review the current modalities of treatment for localized renal cell
      carcinoma. MATERIALS AND METHODS: A literature search for keywords: renal cell
      carcinoma, radical nephrectomy, nephron sparing surgery, minimally invasive
      surgery, and cryoablation was performed for the years 2000 through 2008. The most
      relevant publications were examined. RESULTS: New epidemiologic data and current
      treatment of renal cancer were covered. Concerning the treatment of clinically
      localized disease, the literature supports the standardization of partial
      nephrectomy and laparoscopic approaches as therapeutic options with better
      functional results and oncologic success comparable to standard radical
      resection. Promising initial results are now available for minimally invasive
      therapies, such as cryotherapy and radiofrequency ablation. Active surveillance
      has been reported with acceptable results, including for those who are poor
      surgical candidates. CONCLUSIONS: This review covers current advances in radical
      and conservative treatments of localized kidney cancer. The current status of
      nephron-sparing surgery, ablative therapies, and active surveillance based on
      natural history has resulted in great progress in the management of localized
      renal cell carcinoma.

PMID- 19111073
TI  - Presentation and outcome following radical cystectomy in Hispanics with bladder
      cancer.
AB  - OBJECTIVE: Significant racial and ethnic differences in the epidemiology of
      bladder cancer (BC) exist. Studies have shown African Americans to have lower
      incidence of bladder cancer than Caucasians, but higher incidence of invasive BC.
      Hispanics are the largest minority group in the United States. However, no
      reported studies on bladder cancer among Hispanics are available to date. As our
      center is in a unique position to study BC in Hispanic patients we were prompted
      to assess presentation and outcome of patients undergoing radical cystectomy (RC)
      for BC. MATERIALS AND METHODS: Between January 1992 and May 2006, 448 RC were
      performed. All relevant data were collected and entered into a database. Patients
      were categorized by ethnicity as Hispanic and non-Hispanic White. African
      American and other minority groups were excluded because of the small number.
      Comparative analysis of Hispanic and non-Hispanic White patients was performed.
      RESULTS: 67 (17%) patients were Hispanic. Mean follow-up period was 41 (SD +/-
      40) months. Clinical and pathological data between these two groups were
      compared. Pre-cystectomy T stage was not significantly different between both
      groups. However, after RC incidence of < or = T1 disease in Hispanics was lower
      (22%) than Caucasians (37%). This difference, statistically significant (P =
      0.024) indicates that Hispanics who undergo RC present with higher stage disease.
      Kaplan-Meier log rank test indicated a difference in disease free survival and
      disease specific survival between the two groups but however it did not reach
      statistical significance (Log Rank P = 0.082, P = 0.063). No significant
      difference in overall survival was observed (P = 0.465). CONCLUSIONS: Hispanic
      patients managed with RC for bladder carcinoma present with higher stage disease.

PMID- 19111074
TI  - Asymptomatic bacteriuria among pregnant women referred to outpatient clinics in
      Sanandaj, Iran.
AB  - OBJECTIVES: Determine the prevalence of asymptomatic urinary tract infection
      (AUTI) among pregnant women. We also determined the antibacterial susceptibility
      of the isolates to various antibiotics and associated risk factors in AUTI.
      MATERIALS AND METHODS: One thousand five hundred and five consecutive pregnant
      women were included in the study. Mid-stream urine specimen for complete
      examination of urine was obtained. RESULTS: Of 1505 pregnant women, 134 (8.9%)
      had bacteriuria. The mean age of the all the pregnant women included in the study
      was 28.40 years with a standard deviation of 6.16. Age ranged from 15 to 45 years
      of age. The urine culture of the asymptomatic pregnant women (1505 cases) showed
      growth in only 134 cases (8.9%). Escherichia coli was the commonest organism 79
      (58.96%) followed by CN Staphylococcus 22 (16.8%) and S aureus 18 (13.43%).
      Escherichia coli, which comprised 58.96% (79) of the isolates, were 88.62%,
      87.35%, and 83.55% sensitive to cefotaxime, ciprofloxacin and cefotizoxime
      respectively. Similarly, E. coli were 89%, 70%, and 20% resistant to ampicillin,
      cotrimoxazole, and nitrofurantoin respectively (OR 1.57 95% CI 1.01, 2.44). After
      analyzing, four variables, hemoglobin levels seem to be independently associated
      with asymptomatic bacteriuria (OR = 9.41 (1.65-50.38). CONCLUSION: Prevalence of
      asymptomatic bacteriuria among pregnant women was 8.9%. The predominant organisms
      were Escherichia coli 79 (58.96%), followed by CN Staphylococcus 22 (16.8%). Most
      strains of Escherichia coli showed that they were resistant to ampicillin,
      tetracycline and gentamicin.

PMID- 19111075
TI  - Transcutaneous electrical nerve stimulation (TENS) in the symptomatic management
      of chronic prostatitis/chronic pelvic pain syndrome: a placebo-control randomized
      trial.
AB  - OBJECTIVE: The aim of the study was to investigate the therapeutic efficacy of
      transcutaneous electrical nerve stimulation (TENS) in the symptomatic management
      of chronic prostatitis pain/chronic pelvic pain syndrome. DESIGN: A pretest,
      posttest randomized double blind design was used in data collection. PARTICIPANT:
      Twenty-four patients diagnosed with chronic prostatitis- category IIIA and IIIB
      of the National Institute of Health Chronic Pain (NIH-CP) were referred for
      physiotherapy from the Urology department. INTERVENTION: Pre treatment pain level
      was assessed using the NIH-CP (pain domain) index. The TENS group received TENS
      treatment, 5 times per week for a period of 4 weeks (mean treatment frequency,
      intensity, pulse width and duration of 60 Hz, 100 microS, 25 mA and 20 minutes
      respectively). The Analgesic group received no TENS treatment but continued
      analgesics; the Control group received no TENS and Analgesic but placebo. All
      subjects were placed on antibiotics throughout the treatment period. OUTCOME
      MEASURES: Post-treatment pain level was also assessed using NIH-CP pain index.
      RESULT: Findings of the study revealed significant effect of TENS on chronic
      prostatitis pain at p < 0.05. CONCLUSION: TENS is an effective means of non
      invasive symptomatic management of chronic prostatitis pain.

PMID- 19111076
TI  - Long-term clinical outcome in patients with stage-I nonseminomatous germ cell
      cancer. A critical review of own treatment modalities in a retrospective study.
AB  - PURPOSE: The optimal management of patients with clinical stage I non
      seminomatous germ cell testicular cancer (NSGCT I) was considered controversial
      until the European Germ Cell Cancer Consensus Group determined unambiguous
      treatment strategies. In order to assess the long-term outcome we evaluated the
      data of patients with NSGCT I. MATERIALS AND METHODS: In a retrospective
      evaluation, we included 52 patients with a mean age of 26 years (range 15-58) who
      were treated with different modalities at our department between 1989 and 2003.
      Mean follow-up was 5.9 years (range 2-14 years). After orchiectomy, 39 patients
      were treated with chemotherapy, 7 patients underwent retroperitoneal lymph node
      dissection and 6 men were managed using a surveillance strategy. Survival,
      recurrence rate and time of recurrence were evaluated. The histological staging
      and treatment modality was related to the relapse. RESULTS: Tumor specific
      overall mortality was 3.8%. The mortality and relapse rate of the surveillance
      strategy, retroperitoneal lymph node dissection and chemotherapy was 16.7% / 50%,
      14.3% / 14.3% and 0% / 2.5% respectively. All relapsed patients in the
      surveillance group as well as in the RPLND group had at least one risk factor for
      developing metastatic disease. CONCLUSIONS: Following the European consensus on
      diagnosis and treatment of germ cell cancer in patients with NSGCT Stage I any
      treatment decision must be individually related to the patient according to
      prognostic factors and care capacity of the treating centre. In case of doubt,
      adjuvant chemotherapy should be the treatment of choice, as it provides the
      lowest risk of relapse or tumor related death.

PMID- 19111077
TI  - Sentinel lymph node biopsy in penile cancer: a comparative study using modified
      inguinal dissection.
AB  - INTRODUCTION: In the case of clinically negative inguinal regions in penile
      cancer, the treatments proposed might vary from careful observation to radical
      dissection for all patients. We evaluated the effectiveness of the sentinel lymph
      node biopsy using lymphoscintigraphy in patients with penile cancer and at least
      one negative inguinal region. MATERIALS AND METHODS: In 18 patients, biopsy of
      the sentinel lymph node from the 32 negative inguinal regions and modified
      radical lymphadenectomy in these regions regardless of the biopsy results was
      performed. Clinical staging, pathological results of the sentinel and the other
      lymph nodes removed during lymphadenectomy, tumor behavior, local and inguinal
      recurrence and specific disease mortality were accessed. RESULTS: The mean age of
      the study sample was 57.7 years (44 - 81 years) and the sentinel lymph node
      presented 0% false negative 66% sensitivity, and 79.3% specificity when compared
      with the modified inguinal lymphadenectomy as the gold standard treatment.
      CONCLUSION: Sentinel lymph node biopsy is a feasible method of assessing the
      presence of regional metastasis in patients with penile cancer and clinically
      negative inguinal regions. However, the optimal lymphoscintigraphy technique is
      still in evolution and requires further optimization at high volume centers.

PMID- 19111078
TI  - Pure robotic retrocaval ureter repair.
AB  - PURPOSE: To demonstrate the feasibility of pure robotic retrocaval ureter repair.
      MATERIALS AND METHODS: A 33 year old female presented with right loin pain and
      obstruction on intravenous urography with the classical "fish-hook" appearance.
      She was counseled on the various methods of repair and elected to have a robot
      assisted repair. The following steps are performed during a pure robotic
      retrocaval ureter repair. The patient is placed in a modified flank position,
      pneumoperitoneum created and ports inserted. The colon is mobilized to expose the
      retroperitoneal structures: inferior vena cava, right gonadal vein, right ureter,
      and duodenum. The renal pelvis and ureter are mobilized and the renal pelvis
      transected. The ureter is transposed anterior to the inferior vena cava and a
      pyelopyelostomy is performed over a JJ stent. RESULTS: This patient was
      discharged on postoperative day 3. The catheter and drain tube were removed on
      day 1. Her JJ stent was removed at 6 weeks postoperatively. The postoperative
      intravenous urography at 3 months confirmed normal drainage of contrast medium.
      CONCLUSION: Pure robotic retrocaval ureter is a feasible procedure; however,
      there does not appear to be any great advantage over pure laparoscopy, apart from
      the ergonomic ease for the surgeon as well the simpler intracorporeal suturing.

PMID- 19111079
TI  - Laparoscopic renal surgery in infants and children: is it a feasible and safe
      procedure for all pediatric age groups?
AB  - PURPOSE: Although laparoscopy is considered the mainstay for most renal
      procedures in adults, its role in the pediatric population is still
      controversial, especially for smaller children. We reviewed our experience in
      pediatric renal laparoscopic surgery in three pediatric age groups in an attempt
      to identify if age has an impact on feasibility and surgical outcomes. MATERIALS
      AND METHODS: From November 1995 to May 2006, 144 pediatric laparoscopic renal
      procedures were performed at our institution. The charts of these patients were
      reviewed for demographic data, urologic pathology and surgical procedure, as well
      as perioperative complications and post-operative outcomes. The findings were
      stratified into 3 groups, according to patient age (A: < 1 year, B: 1 to 5 years
      and C: 6-18 years). RESULTS: Median age of the patients was 4.2 years (42 days -
      18 years). We performed 54 nephrectomies, 33 nephroureterectomies, 19 upper pole
      nephrectomies, 11 radical nephrectomies, 22 pyeloplasties and 4 miscellaneous
      procedures. The 3 age groups were comparable in terms of the procedures
      performed. Conversion rates were 0%, 1.4% and 1.9% for groups A, B and C,
      respectively (p = 0.72). Incidence of perioperative complications was 5%, 8.2%
      and 7.8% for age groups A to C, respectively (p = 0.88). CONCLUSIONS: Most renal
      procedures can be performed safely by laparoscopy in the pediatric population,
      with excellent aesthetic and functional outcomes. The morbidity related to the
      procedure was minimal irrespective of the age group.

PMID- 19111080
TI  - Changes in parents' and self-reports of behavioral problems in Brazilian
      adolescents after behavioral treatment with urine alarm for nocturnal enuresis.
AB  - PURPOSE: Compare parents' reports of youth problems (PRYP) with adolescent
      problems self-reports (APSR) pre/post behavioral treatment of nocturnal enuresis
      (NE) based on the use of a urine alarm. MATERIALS AND METHODS: Adolescents (N =
      19) with mono-symptomatic (primary or secondary) nocturnal enuresis group
      treatment for 40 weeks. Discharge criterion was established as 8 weeks with
      consecutive dry nights. PRYP and APSR were scored by the Child Behavior Checklist
      (CBCL) and Youth Self-Report (YSR). RESULTS: Pre-treatment data: 1) Higher number
      of clinical cases based on parent report than on self-report for Internalizing
      Problems (IP) (13/19 vs. 4/19), Externalizing Problems (EP) (7/19 vs. 5/19) and
      Total Problem (TP) (11/19 vs. 5/19); 2) Mean PRYP scores for IP (60.8) and TP
      (61) were within the deviant range (T score > or 60); while mean PRYP scores for
      EP (57.4) and mean APSR scores (IP = 52.4, EP = 49.5, TP = 52.4) were within the
      normal range. Difference between PRYP' and APSR' scores was significant. Post
      treatment data: 1) Discharge for majority of the participants (16/19); 2)
      Reduction in the number of clinical cases on parental evaluation: 9/19
      adolescents remained within clinical range for IP, 2/19 for EP, and 7/19 for TP.
      3) All post-treatment mean scores were within the normal range; the difference
      between pre and post evaluation scores was significant for PRYP. CONCLUSIONS: The
      behavioral treatment based on the use of urine alarm is effective for adolescents
      with mono-symptomatic (primary and secondary) nocturnal enuresis. The study
      favors the hypothesis that enuresis is a cause, not a consequence, of other
      behavioral problems.

PMID- 19111081
TI  - Electromotive drug administration for treatment of therapy-refractory overactive
      bladder.
AB  - PURPOSE: Evaluate the benefits of electromotive drug administration (EMDA) as an
      alternative technique in patients with chronic overactive bladder in terms of
      improvement of symptoms, quality of life, and sexuality. MATERIAL AND METHODS: A
      total of 72 patients with therapy-refractory overactive bladder according to the
      ICS (International Continence Society) definition, were treated by EMDA. The
      regimen consisted of three treatment cycles, each with 3 instillations at 2-week
      intervals. The solution instilled consisted of 100 mL 4% lidocaine, 100 mL
      distilled water, 40 mg dexamethasone, and 2 mL epinephrine. Peri
      interventionally, a urine test and close circulatory monitoring were performed.
      All women underwent urodynamic testing and cystoscopy and kept a voiding diary. A
      comprehensive history was obtained, a quality of life questionnaire administered,
      and a gynecologic examination performed before initiation of therapy. The women
      underwent follow-up at 12 months after the end of therapy. RESULTS: The patients
      had a mean age of 63 (+/- 11.2) years. Bladder capacity improved significantly by
      109 mL (+/- 55 mL) in 51 (71%) patients (p = 0.021). The number of
      micturitions/day decreased significantly to 7 (+/- 2) (p = 0.013). Quality of
      life was improved in 54 patients (75%); p = 0.024) and sexuality in 39 (54%); p =
      0.020). CONCLUSIONS: The results suggest that EMDA can improve both quality of
      life and sexuality in patients with therapy-refractory chronic overactive
      bladder.

PMID- 19111082
TI  - Mixed incontinence: does preoperative urodynamic detrusor overactivity affect
      postoperative quality of life after pubovaginal sling?
AB  - OBJECTIVE: Our purpose was to determine if women with mixed urinary incontinence
      (MUI) and urodynamic detrusor overactivity (DO) have less improvement in urinary
      symptoms after pubovaginal sling surgery (PVS), compared to MUI without DO.
      MATERIALS AND METHODS: Women with preoperative MUI symptoms prior to PVS were
      identified through retrospective review. DO was defined as a symptomatic 5 cm H20
      detrusor pressure or greater rise during urodynamics. MUI patients with and
      without DO before PVS were divided into Groups A and B, respectively. All
      patients had returned a completed Urogenital Distress Inventory 6 (UDI-6)
      questionnaire and a 3-day diary of pad usage before surgery and at each
      postoperative visit. Study endpoints included change in total UDI-6 score, and
      change in number of pad use/day after PVS. RESULTS: 73 patients were identified,
      31 in Group A and 42 in Group B. Mean follow-up after PVS was 15 and 16 months,
      respectively (p = 0.59). Preoperative total UDI-6 scores were 11.8 and 12.7 (p =
      0.30) for Group A and B. Mean changes in total UDI-6 after PVS were - 8.0 and -
      10.2 (p = 0.030), respectively. After PVS, both groups reported similar mean
      reduction in pad/day usage from preoperative baseline (-2.57 vs. --2.49, p =
      0.83). There were no differences between the groups when comparing demographic,
      urodynamic, or operative data. CONCLUSION: MUI patients had improved continence
      and quality of life after PVS. However, MUI patients with DO had less improvement
      in UDI-6 scores after PVS, despite a similar reduction to pad use/day.

PMID- 19111083
TI  - Childhood renal lymphangiectasia.

PMID- 19111104
TI  - Noninvasive ventilation in acute care: controversies and emerging concepts.
      Foreword.

PMID- 19111105
TI  - History and epidemiology of noninvasive ventilation in the acute-care setting.
AB  - Although noninvasive ventilation (NIV) was first used to treat patients with
      acute respiratory failure in the 1940s, the history of this mainstay of today's
      respiratory care armamentarium has mainly been written in the last 20 years.
      There is now a robust evidence base documenting the efficacy of NIV in
      exacerbations of chronic obstructive pulmonary disease, cardiogenic pulmonary
      edema, and acute respiratory failure in immunocompromised patients, and evidence
      in support of NIV in other settings, such as hypoxemic acute respiratory failure
      and the management of patients who decline endotracheal intubation, is
      accumulating rapidly. Efficacy as demonstrated in clinical trials does not
      necessarily translate to clinical effectiveness in practice, however, and
      important barriers need to be overcome if NIV is to realize for the average
      patient the potential it has shown in research studies. However, although the
      expansion of its use in everyday patient care has lagged behind the growth of its
      evidence base, an increasing number of studies document the steadily expanding
      use of NIV in the acute-care setting. This article reviews the history of NIV as
      applied in acutely ill patients and summarizes the studies of NIV outside the
      research setting during the last decade.

PMID- 19111106
TI  - What does it take to have a successful noninvasive ventilation program?
AB  - The use of noninvasive ventilation (NIV) has dramatically increased over the last
      decade. This increase is multifaceted with regard to the number of patients
      receiving NIV and in the increasingly varied disease conditions for which NIV is
      being used. Successful development of an NIV program depends on many variables,
      but perhaps most important is a multidisciplinary approach that incorporates
      experience and education. Many aspects of an NIV program must come together to
      make it successful for both patients and clinicians. Among these are needs
      assessment, institutional buy-in, use of proper equipment, staff and patient
      training, protocols/guidelines, and outcomes. We analyze these issues and
      identify characteristics that produce a successful NIV program.

PMID- 19111107
TI  - Where should noninvasive ventilation be delivered?
AB  - Noninvasive ventilation (NIV) has assumed an important role in the management of
      certain types of respiratory failure in acute-care hospitals. However, the
      optimal location for NIV has been a matter of debate. Some have argued that all
      patients begun on NIV in the acute-care setting should go to an intensive care
      unit (ICU), but this is impractical because ICU beds are often unavailable, and
      it may not be a sensible use of resources. Also, relatively few studies have
      examined the question of location for NIV. One problem is that various units'
      capabilities to deliver NIV differ substantially, even in the same hospital.
      Choosing the appropriate environment for NIV requires consideration of the
      patient's need for monitoring, the monitoring capabilities of the unit, including
      both technical and personnel resources (nursing and respiratory therapy), and the
      staff's skill and experience. In some hospitals NIV is begun most often in the
      emergency department, but is most often managed in an ICU. Step-down units are
      often good locations for NIV, but many institutions do not have step-down units.
      With ICU beds at a premium, many hospitals are forced to manage some NIV patients
      on general wards, which can be safely done with more stable patients if the ward
      is suitably monitored and experienced. When deciding where to locate the patient,
      clinicians must be familiar with the capabilities of the units in their facility
      and try to match the patient's need for monitoring and the unit's capabilities.

PMID- 19111108
TI  - Interfaces and humidification for noninvasive mechanical ventilation.
AB  - During noninvasive ventilation (NIV) for acute respiratory failure, the patient's
      comfort may be less important than the efficacy of the treatment. However, mask
      fit and care are needed to prevent skin damage and air leaks that can
      dramatically reduce patient tolerance and the efficacy of NIV. Choice of
      interface is a major determinant of NIV success or failure. The number and types
      of NIV interface has increased and new types are in development. Oronasal mask is
      the most commonly used interface in acute respiratory failure, followed by nasal
      mask, helmet, and mouthpiece. There is no perfect NIV interface, and interface
      choice requires careful evaluation of the patient's characteristics, ventilation
      modes, and type of acute respiratory failure. Every effort should be made to
      minimize air leaks, maximize patient comfort, and optimize patient-ventilator
      interaction. Technological issues to consider when choosing the NIV interface
      include dead space (dynamic, apparatus, and physiologic), the site and type of
      exhalation port, and the functioning of the ventilator algorithm with different
      masks. Heating and humidification may be needed to prevent adverse effects from
      cool dry gas. Heated humidifier provides better CO(2) clearance and lower work of
      breathing than does heat-and-moisture exchanger, because heated humidifier adds
      less dead space.

PMID- 19111109
TI  - Which ventilators and modes can be used to deliver noninvasive ventilation?
AB  - A wide variety of ventilators and modes can be used to deliver noninvasive
      ventilation (NIV). To navigate successfully through the many options, the
      clinician must first have a clear understanding of the goals of mechanical
      ventilation: namely, safety, comfort, and timely liberation. Examining the
      specific objectives associated with these goals, we can distinguish priorities
      for NIV. This paper reviews the methods of achieving those objectives by
      reviewing the characteristics of ventilation modes and how those characteristics
      are measured in performance-evaluation studies. This review provides the basis
      for a simple procedure for selecting the most appropriate NIV technology for the
      patient and the environment of care.

PMID- 19111110
TI  - The physiologic effects of noninvasive ventilation.
AB  - The physiologic effects of noninvasive ventilation (NIV) on work of breathing
      (WOB) and breathing pattern, respiratory-system mechanics, and hemodynamic
      function were examined via a literature review of clinical studies done between
      1990 and 2008. Forty-one relevant studies were found; the majority examined
      patients with chronic obstructive pulmonary disease, whereas some also included
      patients with restrictive chest-wall disease or acute hypoxic respiratory
      failure. NIV reduced WOB in direct proportion to the level of inspiratory
      pressure-assist, and also by the ability of applied positive end-expiratory
      pressure (PEEP) to counter intrinsic PEEP. In general an inspiratory pressure
      support level of 15 cm H(2)O and a PEEP of 5 cm H(2)O reduced most measures of
      WOB and inspiratory effort toward normal. When set to the same level of
      inspiratory pressure-assist, both pressure-support ventilation and proportional
      assist ventilation effected comparable reductions in WOB. At high levels of
      inspiratory pressure-assist, NIV consistently increased dynamic lung compliance
      and tidal volume, and improved arterial blood gases. The hemodynamic effects of
      NIV are dependent upon the interplay between the type of mask, the level of
      inspiratory pressure-assist and PEEP, and the disease state. In general, patients
      with chronic obstructive pulmonary disease have a higher tendency toward
      decreased cardiac output at high levels of inspiratory pressure-assist, compared
      to those with acute lung injury.

PMID- 19111111
TI  - Noninvasive ventilation for patients presenting with acute respiratory failure:
      the randomized controlled trials.
AB  - Noninvasive ventilation (NIV) in patients with acute respiratory failure (ARF),
      which was originally described decades ago, underwent a rebirth after reports of
      successful use in 1989. Over the following 18 years the literature on NIV has
      grown substantially. This paper summarizes the randomized controlled trials
      (RCTs) on NIV for acute respiratory failure. We conducted an extensive literature
      search and selected RCTs from that search. The results are presented primarily by
      etiology of respiratory failure, but we also include a short section on NIV for
      ARF in immunocompromised patients. The latter studies included patients with
      various etiologies of respiratory failure but with the common comorbidity of
      immunocompromise. Most of the RCTs have studied NIV for exacerbation of chronic
      obstructive pulmonary disease (COPD) or cardiogenic pulmonary edema. In general
      the RCTs have been small and used endotracheal intubation or NIV failure rate as
      primary outcomes. We conclude that NIV for ARF is supported by strong evidence
      from patients with COPD, but there is only weak support for NIV in other patient
      groups, such as immunocompromised patients. For other groups, such as patients
      with asthma, pneumonia, or acute lung injury, RCT-level evidence is lacking or
      does not suggest benefit. Clearly, major gaps remain in our evidence base.

PMID- 19111112
TI  - [The significance of space-time conversion in cardiopulmonary resuscitation].

PMID- 19111113
TI  - [Effects of epidurally administration of morphine at thoracic level on expression
      of tumor necrosis factor-alpha in the lungs in acute myocardial ischemia in
      rats].
AB  - OBJECTIVE: To investigate the expression of tumor necrosis factor-alpha (TNF
      alpha) in lungs following coronary artery occlusion (CAO) and the effect of
      morphine pretreatment via epidural administration on its expression in the rats.
      METHODS: Eighteen adult healthy male Sprague-Dawley (SD) rats were randomly
      divided into sham operation group (S group), CAO group and morphine pretreatment
      group (M group), with 6 in each group. In S group the left anterior descending
      branch of coronary artery was not occluded. In CAO group the left anterior
      descending branch of coronary artery was occluded. In M group the rats were pre
      treated with morphine 60 microg/kg by epidural injection 15 minutes before CAO.
      The right lung was harvested 3 hours after CAO. The expression of TNF-alpha in
      lungs was assessed with immuno- histochemistry and enzyme linked immunosorbent
      assay (ELISA). RESULTS: The immunohistochemistry results showed, compared with S
      group (8.68+/-0.29,1.609+/-0.050), the positive unit and average light density of
      TNF-alpha in CAO group (24.55+/-6.25, 1.844+/-0.027) and M group (11.60+/
      1.21,1.733+/-0.027) were higher significantly, while they were lower
      significantly in M group compared with CAO group (all P<0.01). ELISA results
      showed the level of TNF-alpha in the lung was significantly higher in CAO group
      [(221.58+/-5.23) ng/L] and M group [(103.45+/-4.56) ng/L] than that in S group
      [(47.14+/-1.36) ng/L], while it was significantly lower in M group compared with
      CAO group (all P<0.01). CONCLUSION: Acute myocardial ischemia could cause up
      regulation of TNF-alpha in lungs, which is likely to be mediated by neural
      mechanisms. Opioid and its receptors in spinal cord might be involved in
      modulation of inflammatory reaction in the lung after acute coronary ischemia.

PMID- 19111114
TI  - [Effect of substance P on expression of beta1-adrenergic receptor in cultured rat
      cardiomyocytes].
AB  - OBJECTIVE: To investigate the effect of substance P (SP) on expression of beta1
      adrenergic receptor (beta1-AR) in cultured neonatal rat cardiomyocytes. METHODS:
      Cardiomyocytes were obtained from 1-3 days old Sprague-Dawley (SD) rats and
      cultured for 72 hours. Six wells of the cultured cells were divided into two
      groups (n=3 in each group): control group and SP group (incubated with 10(-7)
      mol/L of SP). Immunocytochemistry was used to detect the expression of beta1-AR
      in cultured rat cardiomyocytes. Fifteen wells of the cultured cells were divided
      into five groups (n=3 in each group): control group and four SP groups (incubated
      with 10(-9), 10 (-8), 10(-7), 10(-6) mol/L of SP respectively). Quantitative
      analysis of the expression of beta1-AR in cultured neonatal rat cardiomyocytes of
      all the groups was performed using flow cytometry. RESULTS: The results of
      immunocytochemistry showed that the expression of beta1-AR in cardiomyocytes in
      SP group was lower than that in control group (positive unit: 179.16+/-48.18 vs.
      205.79+/-117.42, average light density: 128.26+/-22.72 vs. 157.35+/-33.11, both
      P<0.05). The results of flow cytometry showed that significantly lower levels of
      expression of beta1-AR were observed in the groups treated with SP in the
      concentrations ranging from 10 (-8) mol/L to 10 (-6) mol/L (151.85+/
      4.63,135.00+/-6.84,121.41+/-5.22 vs. 161.35+/-3.09,all P<0.05). CONCLUSION: SP
      could down-regulate the expression of beta1-AR in cultured rat cardiomyocytes in
      vitro.

PMID- 19111115
TI  - [A report of 463 in-hospital cardiopulmonary resuscitation based on the "Utstein
      Style"].
AB  - OBJECTIVE: Assessment of outcomes and outcome-related factors of in-hospital
      cardiopulmonary resuscitation (CPR) based on the "Utstein Style". METHODS: The
      study was designed as a prospective, single-institution, registry investigation
      of 463 patients (included adult and pediatric patients) for whom a CPR was
      attempted. RESULTS: The study population consisted of 320 (69.1%) male patients
      and 143 (30.9%) female patients. The age range of 45-54, 55-64, 65-74 were ranked
      the first, the second and third highest. In the past medical history,
      cardiovascular disease and cerebrovascular disorder were two main disorders,
      accounting for 36.3% (168/463) and 9.9% (46/463), respectively. Ventricular
      fibrillation (VF) was the initial electrocardiographic (ECG) change in 74
      patients (16.0%). Two hundred and seventy-three patients received the in-hospital
      CPR, and 190 patients received the pre-hospital CPR. Spontaneous circulation
      returned in 34.6% (160/273) of the in-hospital patients after CPR, and 16.6%
      (77/273) survived for 24 hours and 10.4% (48/273) survived up to the time of
      discharge. The rates of restoration of spontaneous circulation (ROSC) and
      survival of the in-hospital CPR were higher than those of the pre-hospital CPR
      [47.6% (130/273) vs. 15.8% (30/190), 13.9% (38/273) vs. 5.3% (10/190), both
      P<0.01]. CONCLUSION: Prospective "Utstein Style" data collection for CPR is
      proved to be a valuable tool for the evaluation of management and outcome
      following in-hospital cardiopulmonary arrest, but the rate of survival for in
      hospital resuscitation still seems to be too low. The further improvement of CPR
      outcome is necessary.

PMID- 19111116
TI  - [An experimental study on cardiopulmonary resuscitation by cardiac massage under
      diaphragmatic muscle for rabbit with cardiac arrest].
AB  - OBJECTIVE: To compare the hemodynamic effect of standard-cardiopulmonary
      resuscitation (S-CPR) and of CPR by cardiac massage under the diaphragmatic
      muscle (D-CPR), and to evaluate the feasibility of D-CPR. METHODS: Twenty healthy
      New Zealand rabbits were randomly divided into two groups: one group receiving S
      CPR (n=10) and the other group receiving D-CPR (n=10). Cardiac arrest was induced
      by asphyxiation at the end expiration for 8 minutes. After the hemodynamic
      situation was stable for 5 minutes before asphyxiation, the readings of ascending
      aorta systolic pressure (AOS) and diastolic pressure (AOD), transcutaneous oxygen
      saturation (SpO(2)), right atrial systolic pressure (RASP), right atrial
      diastolic pressure (RADP), and electrocardiogram were recorded consecutively to
      the end of the experiment . The mean arterial pressure (MAP) of ascending aorta
      and coronary perfusion pressure (CPP) were calculated. The rate of restoration of
      spontaneous circulation (ROSC) and the survival rate in a short duration of 6
      hours were observed. RESULTS: Five rabbits in S-CPR group and 8 in D-CPR group
      were successfully resuscitated and obtained ROSC (50%, 80%, P=20.05). Six hours
      survival rate was 40% in S-CRP group and 50% in D-CPR group. The comparisons
      between the two groups on AOS, AOD, MAP and CPP respectively showed that at 1
      minute and 5 minutes during resuscitation the respective variables were higher in
      the D-CPR group than that in the S-CPR group (all P<0.05). Compared to the
      hemodynamics before asphyxiation, the MAP and CPP in the D-CPR group increased
      54.1% and 33.4% of basic value at 1 minute, and they were 60.0% and 41.8% at 5
      minutes, while the AOS and AOD in the S-CPR group only increased by an average of
      37.3% and 16.5% at 1 minute, and they were 38.5% and 17.1% at 5 minutes,
      respectively. After ROSC, the hemodynamic variations of the D-CPR rabbits were
      more stable than those of S-CPR rabbits. CONCLUSION: D-CPR can provide higher
      arterial pressure, cardiac output, rate of ROSC and survival rate in a short
      period than S-CPR can induce, so that D-CPR is superior to S-CPR.

PMID- 19111117
TI  - [The influence of anisodamine on cardiopulmonary resuscitation in rat].
AB  - OBJECTIVE: To evaluate the influence of anisodamine (Ani) on restoration of
      spontaneous circulation (ROSC) and cardiopulmonary resuscitation (CPR) rate in a
      randomized, blinded experimental study so as to explore a new treatment for CPR.
      METHODS: Forty-five Sprague-Dawley (SD) rats were randomized to three groups:
      control group (0.9% normal saline), epinephrine (Epi) group and Epi plus Ani
      group (combined group), 15 rats in each group. Ventricular fibrillation (VF) or
      asystole was induced by transoesophageal alternating current stimulation. A
      blinded drug administration and mechanical chest compression were used in this
      study (Epi 200 microg/kg, Ani 10 mg/kg). ROSC rate and resuscitation rate were
      compared among these groups. RESULTS: Combined group had higher ROSC rate(93.3%
      vs. 46.7%), resuscitation rate (80.0% vs.33.3%) and survival rate within 3 hours
      (83.3% vs.20.0%) compared with Epi group (all P<0.05). ROSC occurred only in one
      rat of control group. Mean arterial pressure (MAP) at the beginning of ROSC in
      Epi group was higher compared with combined group (P<0.05). After ROSC, MAP
      decreased in both drug groups, especially after 5 minutes of ROSC, and MAP in Epi
      group was lower than that of combined group. There was difference between the two
      groups till 30 minutes after ROSC (all P<0.05) . CONCLUSION: Administration of
      Epi plus Ani at the beginning of treatment for cardiac arrest could improve ROSC
      rate and resuscitation rate.

PMID- 19111118
TI  - [Effect of intensive insulin treatment on cardiac myocytes of severely scalded
      rats].
AB  - OBJECTIVE: To study the protective effect of intensive insulin treatment on
      cardiac myocytes of severely scalded rats. METHODS: Eighteen model Sprague-Dawley
      (SD) rats were subjected to 30% total body surface area (TBSA) full thickness
      injury, and they were divided into three groups with 6 rats in each group. The
      right jugular vein was cannulated for fluid resuscitation and administration of
      drugs. The rats in burn group were injected with normal saline, the intensive
      insulin group with injection of insulin to maintain plasma glucose content in
      normal range, and the sham burn group received physiologic dose of saline without
      burn injury. Plasma glucose was monitored after burn injury. Rats were sacrificed
      at 6 hours postburn to examine plasma myocardial enzymes spectrum as well as
      histological and ultrastructure changes in cardiac tissue. The expression of p
      Akt was detected by western blotting. RESULTS: Plasma glucose level was
      significantly elevated in burn group within postburn 6 hours as compared with the
      sham burn group, and lowered in intensive insulin group (4.5 approximately 5.2
      mmol/L vs. 7.6 approximately 8.4 mmol/L, P<0.05 or P<0.01). And the intensive
      insulin therapy could effectively inhibit the release of cardiac enzymes [lactate
      dehydrogenase (LDH): (2 369.3+/- 178.9) U/L vs. (2 684.1+/-335.0) U/L, P<0.05;
      alpha-hydroxybutyrate dehydrogenase (alpha-HBD): (576.7+/-219.2) U/L vs. (1
      002.0+/-347.1) U/L, P<0.01; creatine kinase (CK): (1 041.9+/-623.2) U/L vs. (2
      447.1+/-1 183.7) U/L, P<0.01]. The expression of p-Akt was significantly
      strengthened in the intensive insulin group (1.18+/-0.43 vs. 0.24+/-0.11,
      P<0.01). Light microscopic and electron microscopic examinations showed that
      intensive insulin therapy could alleviate the injury to myocardial cells and
      structural changes. CONCLUSION: Intensive insulin treatment possesses protective
      effect on cardiomyocytes after a severe burn, and it is related to its up
      regulation of phosphorylation level of Akt in cardiomyocyte, thus inhibiting the
      damage to myocytes.

PMID- 19111119
TI  - [The influence of JNK inhibitor on hemodynamics after ischemia/reperfusion injury
      to the heart in rats].
AB  - OBJECTIVE: To investigate the effect and mechanism of JNK mitogen-activated
      protein kinases (JNK MAPKs) inhibitor SP 600125 on hemodynamics after
      ischemia/reperfusion (I/R) injury to heart in anesthetized rats. METHODS: Thirty
      six healthy adult Sprague-Dawley (SD) rats were randomly divided into six groups
      (each n=6): sham operation (SO) group, I/R group, three JNK inhibitor groups
      (model groups) and ligustrazine hydrochloride (LH) group. In the SO group, a silk
      suture was passed underneath a main branch of the left coronary artery without
      tying. In the rest groups, the left coronary artery was occluded lasting for 30
      minutes followed by reperfusion for 180 minutes. In the model groups, SP 600125
      was intravenously administered 5 minutes before the end of the ischemia period,
      and continued during reperfusion period with a total dose of 4.7, 14.4 and 47.9
      mg/kg respectively. Control animals received normal saline or LH 30 mg/kg in the
      same manner. The changes in hemodynamics, including heart rate (HR), mean blood
      pressure (MBP), maximal change rate of intraventricular pressure rise/down (+/
      dp/dt max),left ventricular systolic pressure (LVSP), LVDP' [LVDP'=LVSP-left
      ventricular diastolic pressure (LVDP)], left ventricular end-diastolic pressure
      (LVEDP), were determined during I/R. RESULTS: There was no statistical difference
      in hemodynamics among the groups before occluding. The values of HR, MAP, +/
      dp/dt max, LVSP, LVDP' in I/R group were significantly lower than those in SO
      group, and LVEDP was significantly higher. Compared with I/R group, +/-dp/dt max,
      LVSP, LVDP' in model groups and LH group were significantly higher (P<0.05 or
      P<0.01). There was no significant change in HR, MBP and LVEDP after the
      administration of JNK inhibitor or LH. CONCLUSION: Both JNK inhibitor and LH
      ameliorate cardiac systolic and diastolic dysfunction induced by I/R, without
      influence on MBP and HR in anesthetized rats.

PMID- 19111120
TI  - [Protective effect of ulinastatin on myocardium after cardiopulmonary
      resuscitation in rats].
AB  - OBJECTIVE: To investigate the changes in serum creatine kinase isoenzyme (CK-MB)
      and cardiac troponin I (cTnI) levels and the ultrastructure of myocardium, and
      the effect of ulinastatin after cardiopulmonary resuscitation (CPR) in rats.
      METHODS: One hundred and twenty Sprague-Dawley (SD) rats were randomly divided
      into sham operation group, CPR group and ulinastatin group. And each group was
      divided into five subgroups (n=8) according to time points of 0.5, 3, 6, 12, 24
      hours after tracheostomy in sham operation group or after restoration of
      spontaneous circulation (ROSC) in CPR group and ulinastatin group. Cardiac arrest
      (CA) and CPR models were reproduced by asphyxia in CPR group and ulinastatin
      group, with injection of ulinastatin 100 kU/kg via carotid 2 minutes after ROSC
      in ulinastatin group. Normal saline was given in the same dosage as ulinastatin
      in CPR group. Serum samples was taken at each time point of subgroups for
      measuring serum levels of CK-MB and cTnI. The ultrastructure changes in
      myocardium were observed under the electron microscope. RESULTS: The serum levels
      of CK-MB and cTnI were increased from 0.5 hours after ROSC in CPR group and
      ulinastatin group compared with sham operation group ( all P<0.01), and CK-MB
      peaked at 12 hours, then decreased. The serum CK-MB or cTnI levels started to
      decreased from 3 hours or 0.5 hours after ROSC in ulinastatin group compared with
      CPR group (P<0.05 or P<0.01). There were milder pathological changes of
      ultrastructure of myocardium in ulinastatin group than in CPR group. CONCLUSION:
      Ulinastatin could decrease serum levels of CK-MB and cTnI, and alleviate
      myocardial injury after CPR in rats.

PMID- 19111121
TI  - [Study of the effect of p53 and Bcl-2 protein expression in myocardial apoptosis
      in septic rats].
AB  - OBJECTIVE: To explore the significance of p53 and Bcl-2 gene in myocardial
      apoptosis in septic rats. METHODS: Adult male Sprague-Dawley (SD) rats were
      randomly divided into normal control group (n=6), sham operation group (n=6) and
      cecal ligation and puncture (CLP) group (n=24). The sepsis model was reproduced
      by CLP. Rats in CLP group were divided into four subgroups according to the time
      points of 3, 9, 12, and 24 hours after operation, with 6 rats in each subgroup,
      and their hearts were examined according to the experimental protocol. Myocardial
      apoptosis was detected with electron microscopy and terminal deoxynucleotidyl
      transferase-mediated dUTP nick end labeling (TUNEL) technique. Bcl-2 and p53
      protein expression was measured by immunohistochemistry method. RESULTS:
      Myocardial apoptosis index (AI) in septic rats were increased, higher than that
      in normal control group [(1.500+/- 0.141)%] and sham operation group [(1.567+/
      0.258)%, all P<0.05]. The myocardial AI peaked at 12 hours [(55.633+/-2.073)%],
      and lowered at 24 hours [(33.683+/-2.070)a]. The expression level of p53 protein
      in CLP group was lowest at 3 hours [(13.817+/-0.964)%], peaked at 12 hours
      [(80.567+/-5.055)%], and higher than that in normal control group [(0.617+/
      0.232)%] and sham operation group [(0.600+/-0.297)%, all P<0.05 ]. The trend was
      parallel with that of the results of TUNEL. However, the expression level of Bcl
      2 protein peaked at 3 hours [(31.650+/-1.799)%], and was lowest at 12 hours
      [(0.650+/-0.308)%], and lower than that in normal control group [(47.017+/
      0.691)%] and sham operation group [(46.817+/-0.567)%, all P<0.05]. The trend was
      opposite with that of the results of TUNEL. CONCLUSION: Myocardial apoptosis may
      be a mechanism of the pathogenesis of myocardial injury in sepsis. The change in
      the modulating genes p53 and Bcl-2 of apoptosis may serve as indicators of
      myocardial injury. p53 and Bcl-2 gene may be used as an interventional means in
      sepsis to change its outcome.

PMID- 19111123
TI  - [Effects of anisodamine on microcirculation of the asystole rats during the
      cardiopulmonary resuscitation].
AB  - OBJECTIVE: To study the effects of anisodamine (Ani) on microcirculation and
      reperfusion volume of intestine wall in Wistar rats during cardiopulmonary
      resuscitation (CPR) for cardiac arrest (CA). METHODS: Healthy Wistar rats
      subjected to CA and resuscitation were randomly divided into four groups, 15 rats
      in each group. After a 4-minute-non-intervention interval, CPR was started. After
      CPR for 4 minutes the animals in control group received normal saline, group
      epinephrine (Epi) received Epi (bolus dose of 200 microg/kg), Epi plus low dosage
      Ani (Ld Ani) group received Epi plus Ani (bolus dose of 200 microg/kg Epi
      followed by Ani of 5 mg/kg), and Epi plus high dosage Ani (Hd Ani) group received
      Epi plus Ani (bolus dose of 200 microg/kg Epi followed by Ani of 10 mg/kg). The
      recanalization rate of mesenteric arterioles and venules, caliber of the
      recanalized mesentery arteriole and venule, and the reperfusion volume of
      intestine wall were observed in vivo in rats with restoration of spontaneous
      circulation (ROSC). RESULTS: As the rate of recanalization of mesenteric
      arterioles and venules was compared, group Hd Ani (66.6%, 60.0%)>group Ld Ani
      (60.0%, 53.3%)>group control (40.0%, 40.0%)>group Epi (26.7%, 20.0%), and group
      Ld Ani and group Hd Ani was much better than group Epi(all P<0.05). When the
      caliber of arterioles and venules was compared, group Hd Ani>group Ld Ani>group
      control>group Epi 30 minutes and 60 minutes after ROSC. Thirty minutes after
      ROSC, the caliber of arterioles and venules was much larger in group Ld Ani and
      group Hd Ani than that in group Epi (all P<0.05). Sixty minutes after ROSC, there
      was no statistical difference in the caliber of venules between group Ld Ani and
      group Epi, so as between group Ld Ani and group Hd Ani. Reperfusion volume of
      intestine wall in group Ld Ani and group Hd Ani was higher than that in groups
      control and Epi 15 minutes after ROSC, and it kept on to be better up to 60
      minutes after ROSC. CONCLUSION: Administration of Ani at earlier period of
      resuscitation could improve microcirculation of the tissue and raise ROSC rate
      and successful rate of resuscitation.

PMID- 19111124
TI  - [An experimental study of endothelin receptor A expression in brain tissue after
      subarachnoid hemorrhage in rabbits].
AB  - OBJECTIVE: To discuss the relationship between the expression of endothelin
      receptor A (ETRA) in brain tissue and delayed neurological deficit (DND) after
      subarachnoid hemorrhage (SAH). METHODS: Thirty-one Japanese rabbits were divided
      into SAH group (n=15), saline group (n=10), puncture group (n=3), normal control
      group (n=3) randomly, and they subdivided into 1 hour, 3 days, 5 days, 7 days, 10
      days subgroups in both SAH group and saline group. The SAH model was successfully
      reproduced by intracisternal injection of autologous arterial blood twice. When
      the animals were sacrificed by perfusion, brain stems were harvested and prepared
      for immunohistochemical staining and hematoxylin and eosin (HE) staining. The
      pathological changes in the brain tissue were observed with light microscope.
      Then positive-cell counting was used to semi-quantitative analysis. RESULTS: The
      expression of ETRA was not detected nearly in neurons or gliocyte either in
      puncture group (10.6+/-3.9) or in normal group (10.0+/-2.8), while it was
      detected in some cells in saline group. But no significant difference was showed
      among the subgroups in saline group (12.3+/-2.1 lowest vs. 13.3+/-2.6 highest,
      P>0.05) by variance analysis. The expression of ETRA in SAH group was slightly
      stronger after 1 hour (20.1+/-3.5), peaked at 3 days (48.8+/-6.7), and became
      weak gradually after 5 days. The ETRA positive cells at 5 days, 7 days, and 10
      days were 23.1+/-2.9, 22.5+/-4.2 and 19.1+/-2.8 respectively. There were
      significant differences among the values at different time points (P<0.05) in SAH
      group, and the positive cells of ETRA were obviously increased in number in SAH
      group at all time points compared with saline group (all P<0.05). CONCLUSION:
      ETRA is expressed distinctly in the brain tissue, and it may play an important
      role in DND pathogenesis.

PMID- 19111126
TI  - [Decrease in CD4(+)CD25(+) regulatory T cells in patients with acute coronary
      syndrome].

PMID- 19111125
TI  - [A study of the relationship between remodeling of left ventricle and endothelial
      injury and pro-inflammatory mediators in different stages of essential
      hypertension].
AB  - OBJECTIVE: To explore the relationship between left ventricular remodeling and
      vascular endothelial injury and pro-inflammatory mediators in different stages of
      essential hypertension. METHODS: Patients were grouped in according to the
      duration of the disease. The control group consisted of patients with history of
      hypertension for 6 months to 1 year (35 cases), patients with a history of 3
      years were categorized as group A (38 cases), patients with 5-year history as
      group B (32 cases), 8-year history as group C (33 cases), 13-year history as
      group D (34 cases), 15-year history as group E (32 cases). Ultrasonic
      measurements included left atrial diameter (LAD), interventricular septal
      thickness (IVST), left ventricular posterior wall thickness (PWT). Nitric oxide
      (NO, nitrate reductase method), plasma endothelin-1 (ET-1, radioimmunoassay),
      tumor necrosis factor-alpha (TNF-alpha, radioimmunoassay), high-sensitivity C
      reactive protein (hs-CRP, turbidimetry method) and interleukin-6 (IL-6, enzyme
      linked immunosorbent assay) were determined. RESULTS: There was no significant
      difference in ultrasonic measurements, vascular endothelial function and pro
      inflammatory factors between control group and group A (all P>0.05). With
      prolongation of disease, there was obvious change in left ventricular remodeling,
      and the level of NO lowered, but the levels of ET-1, hs-CRP, TNF-alpha, IL-6 were
      elevated (F(LAD)=5.89, F(IVST)=6.58, F(PWT)=9.84, F(NO)=7.58, F(ET-1)=6.21, F( hs
      CRP)=9.80, lzF(TNF-alpha)=12.45, F(IL-6)=6.53, all P<0.01). Compared with the
      control group, LAD, IVST, PWT, and the levels of NO, ET-1, hs-CRP, TNF-alpha, IL
      6 showed statistically significant differences (P<0.05 or P<0.01). There were
      significant differences among groups B, C, D and E when compared one another (all
      P<0.01). CONCLUSION: The longer the duration of essential hypertension, the more
      obvious changes are found in left ventricular remodeling and endothelial injury.
      Pro-inflammatory factors promote endothelial injury and left ventricular
      remodeling. The vascular endothelial injury and pro-inflammatory mediators are
      the main promoters of atherosclerosis.

PMID- 19111127
TI  - [A comparison of influence of homocysteine on peroxidase metabolism between
      elderly patients with or without coronary artery disease].

PMID- 19111128
TI  - [Study on regulation of some important parameters of ventilator during
      cardiopulmonary resuscitation].

PMID- 19111129
TI  - [Protective effect of lidocaine on glutamic acid induced neuronal injury in rat].

PMID- 19111132
TI  - [Study on the pathological changes in striated muscle, cardiac and smooth muscles
      in heatstroke in mice].

PMID- 19111134
TI  - [Effects of Xuebijing injection on platelet membrane glycoprotein CD62P and CD63
      in septic rats].

PMID- 19111141
TI  - Epigenetic deregulation through DNA demethylation seems not to interfere with the
      differentiation of epithelia from pre-gastrulating rat embryos in vitro.
AB  - One of the epigenetic mechanisms controlling differentiation during mammalian
      development is the process of DNA methylation. The differentiation of tissues in
      pre-gastrulating rat embryos cultivated in vitro under the influence of the
      demethylating agent 5-azacytidine (5azaC) was investigated. Eight-day-old Fisher
      rat embryos consisting of epiblast and hypoblast (primitive ectoderm and
      primitive endoderm) were isolated and cultivated in serum-supplemented medium by
      air-lifting method in vitro. A single dose of 5azaC (30 microM) was added to the
      culture medium on day 5 of cultivation. After 14 days, teratoma-like structures
      developed and were processed by routine histology. When compared to controls, the
      explants treated with 5azaC showed a statistically significant higher incidence
      of neuroblasts, myotubes, cartilage, and blood islands. On the other hand, the
      incidence of stratified squamous, columnar and glandular epithelium was not
      statistically different from controls. It seems that differentiation of epithelia
      was not sensitive to DNA demethylation caused by 5azaC like differentiation of
      other tissues, especially mesodermal derivatives.

PMID- 19111143
TI  - Epidemiology of nonmelanoma and melanoma skin cancer in Zagreb, Croatia.
AB  - The purpose of this retrospective and hospital-based study was to evaluate the
      epidemiology of nonmelanoma and melanoma skin cancer at University Department of
      Dermatology and Venereology, Zagreb University Hospital Center and School of
      Medicine during the 2003-2006 period. The study yielded population based results
      on 2911 cases of skin tumors in 2402 patients out of 16938 biopsies performed at
      Laboratory of Dermatologic Histopathology, University Department of Dermatology
      and Venereology, Zagreb University Hospital Center nd School of Medicine during
      the study period. All newly diagnosed invasive and in situ skin cancers were
      recorded by use of the histopathology record forms. Basal cell carcinoma was most
      commonly identified in the histopathology material (n=2002), followed by squamous
      cell carcinoma (n=533), melanoma (n=46) and cutaneous lymphoma (n=35). Other,
      less common tumors were noted. The number of tumors, and differences in age, sex
      and localization were analyzed. During the study period, there was no increase in
      the total number of cases recorded: 4305, 4202, 4116 and 4315, respectively.
      Study results showed skin tumors to be mostly diagnosed in elderly population
      (median age, 71 years). There were no significant sex differences, with the
      exception of the adult age group in 2006. As expected, skin tumors were mostly
      found in sun-exposed areas with some specific localization of individual tumor
      types. Study results were consistent with recent literature data.

PMID- 19111144
TI  - Drug-resistant herpes simplex virus in HIV infected patients.
AB  - Herpes simplex virus type 2 (HSV2) infection is a major source of morbidity in
      human immunodeficiency virus (HIV)-infected patients, since reactivations -
      whether symptomatic or asymptomatic - are associated with increased HIV viral
      load and viral shedding. Acyclovir, valacyclovir and famcyclovir are indicated
      for the treatment of HSV2 in HIV patients. This class of drugs has been shown to
      enhance survival in HIV-infected individuals. However, with the emergence of drug
      resistant strains of HSV2, the rates of resistance among HIV patients are almost
      ten-fold those in immunocompetent individuals, comparing 0.6% to 6%. These HSV2
      infections tend to be more severe and to recur. More ominously, disease
      progression of HIV is promoted by concurrent infection with HSV2. Intravenous
      foscarnet and cidofovir may be used for acyclovir-resistant HSV; however,
      resistance to these drugs has been documented. Newer therapies such as the toll
      like receptor agonist imiquimod and immunomodulating dipeptides offer promise for
      the treatment of HSV2 in HIV-infected individuals.

PMID- 19111145
TI  - Effect of different epinephrine concentrations on local bleeding and hemodynamics
      during dermatologic surgery.
AB  - In local anesthesia, various epinephrine concentrations are applied for its
      vasoconstrictive effect. This study was conducted to observe the effect of
      epinephrine on intraoperative bleeding and also to evaluate hemodynamic changes
      during skin surgery. Ninety-six patients scheduled for skin surgery under local
      anesthesia were divided into three groups administered three different
      concentrations of epinephrine (1:50,000, 1:100,000 and 1:200,000) with 1%
      lidocaine (an average of 5.7 mL). The rate of bleeding and hemodynamic changes
      were assessed during surgical procedure. The surgeon's rating of intraoperative
      bleeding was significantly lower in the group administered epinephrine
      concentration of 1:50,000 as compared with the group on epinephrine concentration
      of 1:200,000. However, there was no significant difference between the groups
      administered epinephrine concentrations of 1:200,000 and 1:100,000. Except for
      diastolic blood pressure at 1 min after injection of local anesthetics, transient
      changes of hemodynamic parameters were observed, with no statistically
      significant difference among the three anesthetic solutions used. It is concluded
      that, for local anesthesia, the rate of intraoperative bleeding is influenced by
      epinephrine concentration, and that 1:50,000 epinephrine provides optimal
      clinical efficacy for the local bleeding control during dermatologic surgery.

PMID- 19111146
TI  - Drug induced linear IgA disease with unusual features: Koebner phenomenon, local
      insulin sensitivity and annular blister of the nipples.
AB  - Linear IgA disease is an autoimmune subepidermal bullous disease in which linear
      IgA deposits are found at the basement membrane zone. It is classically
      idiopathic but may be drug induced. We report on a patient with drug induced
      linear IgA disease who exhibited certain unusual and interesting clinical
      features including isomorphic Koebner response, annular blister of the nipples
      and local insulin sensitivity. To the best of our knowledge, these clinical
      features have not yet been reported in linear IgA disease.

PMID- 19111147
TI  - Endometriosis of umbilical cicatrix: case report and review of the literature.
AB  - Umbilical endometriosis has an estimated incidence of 0.5%-1% of all patients
      with endometrial ectopia. It is a very rare disease, but should be considered on
      the differential diagnosis of umbilical lesions. We report on a case of
      spontaneous umbilical endometriosis in a 38-year-old woman, with a dark brown
      nodule periodically bleeding, associated with severe abdominal pain. There was no
      history of endometriosis and she had not been pregnant before. Laparoscopic
      visualization of pelvic cavity showed bilateral ovarian endometrioma (it was
      removed while sparing the ovaries). Surgical treatment proved effective.
      Cutaneous endometriosis could be a sign of internal endometriosis. Presentations
      may be atypical and pose diagnostic difficulty, mimicking other acute diseases,
      e.g., skin neoplasm, folliculitis, etc., but it should be suspected in any female
      presenting with a painful or bleeding mass close to the umbilicus or abdominal
      surgical scar.

PMID- 19111148
TI  - Subcutaneous dirofilariasis caused by Dirofilaria repens diagnosed by
      histopathologic and polymerase chain reaction analysis.
AB  - A 31-year-old man with a history of intravenous drug abuse presented with an
      inflamed subcutaneous nodule in his left thigh. The nodule measured up to 1.2 cm
      in largest diameter. Under the clinical impression of an inflamed epidermal cyst
      or a subcutaneous abscess, surgical excision was performed. Histopathologic
      examination of the nodule and subsequent polymerase chain reaction (PCR) analysis
      revealed the presence of the helminth Dirofilaria (D.) repens, a member of the
      family Filarioidea. Dirofilariasis is a parasitosis caused by D. repens and D.
      immitis that most frequently affects canines. It can rarely be found in humans,
      usually in the form of a subcutaneous nodule. In Europe, most cases of human
      dirofilariasis have been detected in the Mediterranean countries, Ukraine and
      Russia, but sporadic cases have also been reported in central and north European
      countries. Dirofilariasis must be distinguished from other forms of filarial
      disease such as onchocercosis and Wuchereria bancrofti filariasis. Diagnosing
      dirofilariasis purely by histopathology has its pitfalls, especially when the
      morphology of the nematode is altered due to inflammatory response or surgical
      artifacts. PCR analysis offers an opportunity to confirm dirofilariasis and
      identify the dirofilarial species as well. Briefly, we conclude that a diagnosis
      of subcutaneous dirofilariasis should be considered in cases of subcutaneous mass
      in an endemic area of animal dirofilariasis.

PMID- 19111149
TI  - Seborrheic dermatitis - an early and common skin manifestation in HIV patients.
AB  - Seborrheic dermatitis is a common dermatosis occurring on the scalp, face and
      chest. In the general population, the prevalence of seborrheic dermatitis varies
      between 3% and 5%, while in HIV positive patients there is an increased
      prevalence of seborrheic dermatitis ranging between 30% and 83%. Seborrheic
      dermatitis occurs early in the course of HIV disease and may be an initial
      clinical marker of HIV infection.

PMID- 19111150
TI  - Obesity and allergic diseases.
AB  - In the last few decades, the prevalence of allergic diseases, asthma, allergic
      rhinoconjunctivitis and atopic dermatitis in particular, has been observed to
      increase in urban settings. In addition, epidemiological data show the proportion
      of overweight individuals to rise in the last two decades. Obesity and overweight
      are a major public health problem not only in industrialized countries but also
      in developing ones because the morbidity and mortality rates are greater in the
      obese. An increased body mass index is considered a risk factor for the
      occurrence of myocardial infarction, stroke, atherosclerosis, hypertension,
      insulin resistance, dyslipidemia and some types of carcinoma. An ever greater
      body of available data point to the possible association of allergic diseases
      with obesity and overweight. Impaired immune tolerance is considered to be a
      sequel of immune changes due to the activity of adipokines, bioactive molecules
      secreted in white adipose tissue. About 50 adipokines are currently known to be
      secreted in adipose tissue, some of them belonging to the group of cytokines such
      as tumor necrosis factor alpha and interleukin-6. The association between obesity
      and allergic diseases has not yet been fully clarified. While the observations
      recorded to date should not be neglected, additional studies are necessary to
      help understand the complex function of adipokines involved in allergic events.

PMID- 19111151
TI  - Subungual melanoma: a deceptive disorder.
AB  - Subungual melanoma is an uncommon form of acral melanoma that arises within the
      nail bed. The incidence for acral melanomas is similar worldwide, but the
      proportion is higher in dark-skinned individuals. The subungual form represents
      about 2% of cutaneous non-sun induced melanomas in the western world, and up to
      75% in Africans, 10% in Japanese, and 25% in the Chinese of Hong Kong. Up to 33%
      of subungual melanomas are amelanotic. Black pigmentation of the adjacent nail
      fold, termed Hutchinson's sign, may be a diagnostic clue. Non-specific features
      and symptoms along with a high incidence of amelanosis often lead to delayed
      diagnosis, disease progression, and a poor prognosis with challenging treatment
      options.

PMID- 19111158
TI  - 50th anniversary of the Journal of Molecular Biology.

PMID- 19111159
TI  - Journal of Molecular Biology: 50 years of success made possible by our editors,
      reviewers, authors and readers.

PMID- 19111161
TI  - Autoimmune diabetes mellitus--much progress, but many challenges.

PMID- 19111160
TI  - Diffusion abnormalities in adolescents and young adults with a history of heavy
      cannabis use.
AB  - BACKGROUND: There is growing evidence that adolescence is a key period for
      neuronal maturation. Despite the high prevalence of marijuana use among
      adolescents and young adults in the United States and internationally, very
      little is known about its impact on the developing brain. Based on neuroimaging
      literature on normal brain developmental during adolescence, we hypothesized that
      individuals with heavy cannabis use (HCU) would have brain structure
      abnormalities in similar brain regions that undergo development during late
      adolescence, particularly the fronto-temporal connection. METHOD: Fourteen young
      adult males in residential treatment for cannabis dependence and 14 age-matched
      healthy male control subjects were recruited. Patients had a history of HCU
      throughout adolescence; 5 had concurrent alcohol abuse. Subjects underwent
      structural and diffusion tensor magnetic resonance imaging. White matter
      integrity was compared between subject groups using voxelwise and fiber
      tractography analysis. RESULTS: Voxelwise and tractography analyses revealed that
      adolescents with HCU had reduced fractional anisotropy, increased radial
      diffusivity, and increased trace in the homologous areas known to be involved in
      ongoing development during late adolescence, particularly in the fronto-temporal
      connection via arcuate fasciculus. CONCLUSIONS: Our results support the
      hypothesis that heavy cannabis use during adolescence may affect the trajectory
      of normal brain maturation. Due to concurrent alcohol consumption in five HCU
      subjects, conclusions from this study should be considered preliminary, as the
      DTI findings reported here may be reflective of the combination of alcohol and
      marijuana use. Further research in larger samples, longitudinal in nature, and
      controlling for alcohol consumption is needed to better understand the
      pathophysiology of the effect of cannabis on the developing brain.

PMID- 19111162
TI  - CD3 antibodies as unique tools to restore self-tolerance in established
      autoimmunity their mode of action and clinical application in type 1 diabetes.

PMID- 19111163
TI  - GAD65 autoimmunity-clinical studies.
AB  - Type 1 diabetes (T1D) in children and particularly in teenagers and adults is
      strongly associated with autoreactivity to the Mr 65,000 isoform of glutamic acid
      decarboxylase (GAD65). Autoantibodies to GAD65 are common at the time of clinical
      diagnosis and may be present for years prior to the onset of hyperglycemia. GAD65
      autoantibodies predict conversion to insulin dependence when present in patients
      classified with type 2 diabetes nowadays more often referred to as patients with
      latent autoimmune diabetes in the adult (LADA) or type 1,5 diabetes. Analyses of
      T cells with HLA DRB1 0401-tetramers with GAD65-specific peptides as well as of
      anti-idiotypic GAD65 autoantibodies suggest that GAD65 autoreactivity is common.
      The immunological balance is disturbed and the appearance of GAD65 autoantibodies
      represents markers of autoreactive loss of pancreatic beta cells. Extensive
      experimental animal research, in particular of the Non-obese diabetic (NOD)
      mouse, showed that GAD65 therapies reduce insulitis and prevent spontaneous
      diabetes. Recombinant human GAD65 produced by current Good Manufacturing Practice
      (cGMP) and formulated with alum was found to be safe in Phase I and II placebo
      controlled, double-blind, randomized clinical trials. The approach to modulate
      GAD65 autoreactivity with subcutaneous immunotherapy (SCIT) showed promise as
      alum-formulated GAD65 induced a dose-dependent reduction in the disappearance
      rate of endogenous residual C-peptide production. Additional controlled clinical
      trials are needed to uncover the mechanisms by which subcutaneous injections of
      recombinant human GAD65 may alter GAD65 autoreactivity.

PMID- 19111164
TI  - CD8+ T cells in type 1 diabetes.
AB  - Type 1 diabetes (T1D), an autoimmune disease once thought to be mediated
      exclusively by beta cell-specific CD4+ T cells, is now recognized as one in which
      autoreactive CD8+ T cells play a fundamental role. In the nonobese diabetic (NOD)
      mouse model, CD8+ T effector cells take centre stage in the destruction of
      pancreatic beta cells and contribute to sustaining islet inflammation. Recent
      investigations have elucidated the mechanisms underlying the activation, homing,
      and beta cell destructive properties of this type of cells. Another important
      area is the development and testing of novel preemptive or therapeutic "vaccines"
      that, by targeting effector and/or regulatory autoreactive CD8+ T cell
      specificities may be able to induce immunological tolerance to beta cells. In
      humans, our understanding of the role of CD8+ T cells in T1D is also growing,
      through genetic linkage analyses, as well as epitope identification and
      characterization of disease-relevant CD8+ T cell responses in patient blood
      samples. The following review discusses these important advances and how they can
      converge towards the goal of developing an antigen-specific immunotherapy for
      T1D.

PMID- 19111165
TI  - Dysrulation of T cell peripheral tolerance in type 1 diabetes.
AB  - Type 1 diabetes (T1D) is a T cell-mediated autoimmune disease in which the
      insulin producing beta cells are destroyed. The breakdown of beta cell-specific
      self-tolerance by T cells involves a number of dysregulated events intrinsic and
      extrinsic to T cells. Herein, we review the key mechanisms that drive beta cell
      autoimmunity, with an emphasis on events that influence the expansion and
      differentiation of pathogenic T cells in the periphery.

PMID- 19111166
TI  - Gene-gene interactions in the NOD mouse model of type 1 diabetes.
AB  - Human genome wide association studies (GWAS) have recently identified at least
      four new, non-MHC-linked candidate genes or gene regions causing type one
      diabetes (T1D), highlighting the need for functional models to investigate how
      susceptibility alleles at multiple common genes interact to mediate disease.
      Progress in localizing genes in congenic strains of the nonobese diabetic (NOD)
      mouse has allowed the reproducible testing of gene functions and gene-gene
      interactions that can be reflected biologically as intrapathway interactions, for
      example, IL-2 and its receptor CD25, pathway-pathway interactions such as two
      signaling pathways within a cell, or cell-cell interactions. Recent studies have
      identified likely causal genes in two congenic intervals associated with T1D,
      Idd3, and Idd5, and have documented the occurrence of gene-gene interactions,
      including "genetic masking", involving the genes encoding the critical immune
      molecules IL-2 and CTLA-4. The demonstration of gene-gene interactions in
      congenic mouse models of T1D has major implications for the understanding of
      human T1D since such biological interactions are highly likely to exist for human
      T1D genes. Although it is difficult to detect most gene-gene interactions in a
      population in which susceptibility and protective alleles at many loci are
      randomly segregating, their existence as revealed in congenic mice reinforces the
      hypothesis that T1D alleles can have strong biological effects and that such
      genes highlight pathways to consider as targets for immune intervention.

PMID- 19111167
TI  - RNA turnover in eukaryotes: nucleases, pathways and analysis of mRNA decay.
      Preface.

PMID- 19111168
TI  - Analysis of mRNA decapping.
AB  - The modulation of mRNA decay is a critical determinant in the regulation of gene
      expression. mRNAs in eukaryotes are primarily degraded by two major
      exonucleolytic pathways: the 5' to 3'-and the 3' to 5'-pathways, both of which
      are initiated by removal of the polyadenylated (poly(A)) tail. Hydrolysis of the
      5'-cap structure, termed decapping, is a key step in the demise of mRNA. Two
      major decapping enzymes with distinct activities and substrate requirements have
      been identified. Dcp2 hydrolyzes the cap structure on an intact mRNA in the 5' to
      3'-decay pathway; Dcp2 scavenges the residual cap oligonucleotide resulting from
      the 3' to 5'-decay pathway, as well as hydrolyzes the decapping product generated
      by Dcp2. In this chapter, we describe the methods for monitoring Dcp2 and DcpS
      decapping activities of bacterially expressed and endogenous human decapping
      enzymes.

PMID- 19111169
TI  - A kinetic assay to monitor RNA decapping under single- turnover conditions.
AB  - The stability of all RNA polymerase II transcripts depends on the 5'-terminal cap
      structure. Removal of the cap is a prerequisite for 5' to 3'-decay and is
      catalyzed by distinct cellular and viral decapping activities. Over the past
      decade, several decapping enzymes have been characterized through functional and
      structural studies. An emerging theme is that function is regulated by protein
      interactions; however, in vitro assays to dissect the effects on enzyme activity
      are unavailable. Here we present a kinetic assay to monitor decapping by the
      heterodimeric yeast Dcp1/Dcp2 complex. Kinetic constants related to RNA binding
      and the rate of the catalytic step can be determined with recombinant enzyme and
      cap-radiolabeled RNA substrate, allowing substrate specificity and the role of
      activating factors to be firmly established.

PMID- 19111170
TI  - Purification and analysis of the decapping activator Lsm1p-7p-Pat1p complex from
      yeast.
AB  - Biochemical analysis of the components of the mRNA decay machinery is crucial to
      understand the mechanisms of mRNA decay. The Lsm1p-7p-Pat1p complex is a key
      activator of decapping in the 5' to 3'-mRNA decay pathway that is highly
      conserved in all eukaryotes. The first step in this pathway is poly(A) shortening
      that is followed by the selective decapping and subsequent 5' to 3'
      exonucleolytic degradation of the oligoadenylated mRNAs. Earlier studies
      suggested that the Lsm1p-7p-Pat1p complex preferentially associates with
      oligoadenylated mRNAs and facilitates their decapping in vivo (Tharun and Parker,
      2001a; Tharun et al., 2000). They also showed that the Lsm1p through Lsm7p and
      Pat1p are involved in protecting the 3'-ends of mRNAs in vivo from trimming (He
      and Parker, 2001). Therefore, to gain better insight into the biologic function
      of the Lsm1p-7p-Pat1p complex, it is important to determine its in vitro RNA
      binding properties. Here I describe the methods we use in my laboratory for the
      purification and in vitro RNA binding analysis of this complex from the budding
      yeast Saccharomyces cerevisiae. Purification was achieved with tandem affinity
      chromatography using a split-tag strategy. This involved use of a strain
      expressing FLAG-tagged Lsm1p and 6xHis-tagged Lsm5p and purification by a two
      step procedure with an anti-FLAG antibody matrix followed by a Ni-NTA matrix. The
      purified complex was analyzed for its RNA binding properties with gel mobility
      shift assays. Such analyses showed that this complex has the intrinsic ability to
      distinguish between oligoadenylated and polyadenylated RNAs and that it binds
      near the 3'-ends of RNAs (Chowdhury et al., 2007). These observations, therefore,
      highlighted the importance of the intrinsic RNA binding properties of this
      complex as key determinants of its in vivo functions.

PMID- 19111171
TI  - Reconstitution of recombinant human LSm complexes for biochemical, biophysical,
      and cell biological studies.
AB  - Sm and Sm-like (LSm) proteins are an ancient family of proteins present in all
      branches of life. Having originally arisen as RNA chaperones and stabilizers, the
      family has diversified greatly and fulfills a number of central tasks in various
      RNA processing events, ranging from pre-mRNA splicing to histone mRNA processing
      to mRNA degradation. Defects in Sm/LSm protein-containing ribonucleoprotein
      assembly and function lead to severe medical disorders like spinal muscular
      atrophy. Sm and LSm proteins always assemble into and function in the form of
      ringlike hexameric or heptameric complexes whose composition and architecture
      determine their intracellular location and RNA and effector protein binding
      specificity and function Sm/LSm complexes that have been assembled in vitro from
      recombinant components provide a flexible and invaluable tool for detailed cell
      biological, biochemical, and biophysical studies on these biologically and
      medically important proteins. We describe here protocols for the construction of
      bacterial LSm coexpression vectors, expression and purification of LSm proteins
      and subcomplexes, and the in vitro reconstitution of fully functional human LSm1
      7 and LSm2-8 heptameric complexes.

PMID- 19111172
TI  - Regulated deadenylation in vitro.
AB  - The 3'-poly(A) tail, found on virtually all mRNAs, is enzymatically shortened by
      a process referred to as "deadenylation." Deadenylation is a widespread means of
      controlling mRNA stability and translation. The enzymes involved-so-called
      deadenylases-are surprisingly diverse. They are controlled by RNA sequences
      commonly found in 3'-untranslated regions (UTRs), which bind regulatory factors.
      Both RNA-binding proteins and microRNAs accelerate deadenylation of specific
      mRNAs. In some cases, regulators enhance deadenylation by binding to and
      recruiting specific deadenylases to the target mRNA. The many hundreds of
      potential regulators encoded in mammalian genomes (both RNA-binding proteins and
      microRNAs) and the numerous deadenylases, coupled with the many potential
      regulatory sites represented in 3' UTRs of mRNAs, provide fertile ground for
      regulated deadenylation. Recent global studies of poly(A) regulation support this
      conclusion. Biochemical and genetic approaches will be essential for exploring
      regulated deadenylation. The methods we describe focus on the reconstruction in
      vitro of regulated deadenylation with purified components from yeast. We discuss
      broadly the strategies, problems, and history of in vitro deadenylation systems.
      We combine this with a more detailed discussion of the purification, activity,
      and regulation of the Saccharomyces cerevisiae Ccr4p-Pop2p deadenylase complex
      and its regulation by PUF (Pumilio and Fem-3 binding factor) RNA-binding
      proteins.

PMID- 19111173
TI  - Cell-free deadenylation assays with Drosophila embryo extracts.
AB  - Deadenylation initiates degradation of most mRNAs in eukaryotes. Regulated
      deadenylation of an mRNA plays an important role in translation control as well,
      especially during animal oogenesis and early embryonic development. To
      investigate the mechanism of sequence-dependent deadenylation, we established an
      in vitro system derived from 0- to 2-h-old Drosophila embryos. These extracts
      faithfully reproduce several aspects of the regulation of nanos mRNA: They
      display translation repression and deadenylation both mediated by the same
      sequences within the nanos 3' UTR. Here, we describe detailed protocols for
      preparing Drosophila embryo extracts, and their use in deadenylation assays
      exemplified with exogenous RNA substrates containing the nanos 3' UTR.

PMID- 19111174
TI  - Measuring CPEB-mediated cytoplasmic polyadenylation-deadenylation in Xenopus
      laevis oocytes and egg extracts.
AB  - The regulation of poly(A) tail length is one important mechanism for controlling
      gene expression during early animal development. In Xenopus oocytes, the
      polyadenylation-deadenylation of several essential dormant mRNAs, including
      cyclin B1 mRNA, are controlled by the cis-acting cytoplasmic polyadenylation
      element (CPE) and the hexanucleotide AAUAAA through their associations with
      protein factors CPEB and CPSF, respectively. CPE-containing, as well as CPE
      lacking, pre-mRNAs acquire long poly(A) tails in the nucleus; after their export
      to the cytoplasm, there is subsequent deadenylation of CPE-containing mRNAs that
      is controlled by the CPEB-associated factor PARN, a poly(A)-specific
      ribonuclease. In general, re-adenylation after meiotic maturation of CPE
      containing mRNAs is mediated by Gld2, a poly(A) polymerase. Moreover, embryonic
      poly(A)-binding protein, ePAB, is required for the subsequent elongation and
      stabilization of the poly(A) tail against PARN and other deadenylating enzymes.
      In this chapter, we present detailed information for measuring CPEB-mediated
      cytoplasmic polyadenylation-deadenylation in Xenopus laevis oocytes and egg
      extracts.

PMID- 19111175
TI  - The preparation and applications of cytoplasmic extracts from mammalian cells for
      studying aspects of mRNA decay.
AB  - HeLa S100 cytoplasmic extracts have been shown to effectively recapitulate many
      aspects of mRNA decay. Given their flexibility and the variety of applications
      readily amenable to extracts, the use of such systems to probe questions relating
      to the field of RNA turnover has steadily increased over time. Cytoplasmic
      extract systems have contributed greatly to the field of RNA decay by allowing
      valuable insight into RNA-protein interactions involving both the decay machinery
      and stability/instability factors. A significant advantage of these systems is
      the ability to assess the behaviors of several transcripts within an identical
      static environment, reducing errors within experimental replications. The impact
      of the cytoplasmic extract/in vitro RNA decay technology may be further advanced
      through manipulations of the extract conditions or the environment of the cells
      from which it is made. For instance, an extract may be produced from cells after
      depletion of a specific factor by RNAi, giving insight into the role of that
      factor in a particular process. The goals of this chapter are threefold. First,
      we will familiarize the reader with the process of producing high-quality,
      reliable HeLa-Cell cytoplasmic extracts. Second, a method for the standardization
      of independent extracts is described in detail to allow for dependable extract-to
      extract comparisons. Finally, the use and application of cytoplasmic extracts
      with regard to assaying several aspects of mRNA turnover are presented.
      Collectively these procedures represent an important tool for the mechanistic
      analysis of RNA decay in mammalian cells.

PMID- 19111176
TI  - In vitro assays of 5' to 3'-exoribonuclease activity.
AB  - The major cytoplasmic 5' to 3'-exoribonuclease activity is carried out by the
      Xrn1 protein in eukaryotic cells. A number of different approaches can be used to
      study multifunctional Xrn1 protein activity in vitro. In this chapter, we
      concentrate on methods used in our laboratory to analyze Xrn1 5' to 3'
      exoribonuclease activity. Some of these techniques may also be suitable for
      detecting 3' to 5'-exoribonuclease or endoribonuclease activity. For these
      reasons, these assays can be used to isolate new proteins with ribonuclease
      activity and, when performed in combination with in vivo experiments, will
      contribute to a new level of understanding of the function of these factors.

PMID- 19111178
TI  - Biochemical studies of the mammalian exosome with intact cells.
AB  - A key component responsible for 3'- to 5'-RNA turnover in eukaryotic cells is the
      exosome, a multisubunit complex present in both the nucleus and cytoplasm of the
      cell. Here we describe several methods that can be applied to study the structure
      and function of the exosome in mammalian cell lines. The mammalian two-hybrid
      system has been successfully used to identify protein-protein interactions
      between exosome core components. Cell and glycerol gradient fractionation
      procedures are described that allow the identification and characterization of
      different exosome subsets. Finally, a protocol to study the function of the
      exosome in RNA turnover with RNA interference is presented.

PMID- 19111177
TI  - Reconstitution of RNA exosomes from human and Saccharomyces cerevisiae cloning,
      expression, purification, and activity assays.
AB  - Eukaryotic RNA exosomes participate in 3' to 5'-processing and degradation of RNA
      in the nucleus and cytoplasm. RNA exosomes are multisubunit complexes composed of
      at least nine distinct proteins that form the exosome core. Although the
      eukaryotic exosome core shares structural and sequence similarity to
      phosphorolytic archaeal exosomes and bacterial PNPase, the eukaryotic exosome
      core has diverged from its archaeal and bacterial cousins and appears devoid of
      phosphorolytic activity. In yeast, the processive hydrolytic 3' to 5'
      exoribonuclease Rrp44 associates with exosomes in the nucleus and cytoplasm.
      Although human Rrp44 appears homologous to yeast Rrp44, it has not yet been shown
      to associate with human exosomes. In the nucleus, eukaryotic exosomes interact
      with Rrp6, a distributive hydrolytic 3' to 5'-exoribonuclease. To facilitate
      analysis of eukaryotic RNA exosomes, we will describe procedures used to clone,
      express, purify, and reconstitute the nine-subunit human exosome and nine-, ten-,
      and eleven-subunit yeast exosomes. We will also discuss procedures to assess
      exoribonuclease activity for reconstituted exosomes.

PMID- 19111179
TI  - Determining in vivo activity of the yeast cytoplasmic exosome.
AB  - A 3'-exoribonuclease complex, termed the exosome, has important functions in the
      cytoplasm, as well as in the nucleus, and is involved in 3'-processing and/or
      decay of many RNAs. This chapter will discuss methods to study cytoplasmic
      exosome function in yeast with in vivo approaches. The first section will
      describe mutants that are available to study the processing or decay of a
      specific RNA by the nuclear or cytoplasmic exosome. The second section will
      discuss methods to determine whether the cytoplasmic exosome is functional under
      a specific condition(s) with reporter mRNAs that are known substrates of this
      complex.

PMID- 19111180
TI  - Approaches for studying PMR1 endonuclease-mediated mRNA decay.
AB  - Although most eukaryotic mRNAs are degraded by exonucleases acting on either end
      of the molecule, a subset of mRNAs undergo endonuclease cleavage within the mRNA
      body. Endonuclease cleavage can be activated by cellular stress, extracellular
      signals, or by ribosome stalling, as might occur at a premature termination
      codon. Only a few eukaryotic mRNA endonucleases have been identified, and of
      these, polysomal ribonuclease 1 (PMR1) is the best characterized. A notable
      feature of PMR1-mediated mRNA decay is that it acts on specific mRNAs while they
      are engaged by translating ribosomes. This chapter begins with several procedures
      used to characterize in vivo endonuclease cleavage of any mRNA by any
      endonuclease. These include approaches for identifying the 5'-end(s) downstream
      of an endonuclease cleavage site (S1 nuclease protection and primer extension),
      and a ligation-mediated RT-PCR approach developed in our laboratory for
      identifying the 3'-ends upstream of a cleavage site. We then describe a number of
      approaches used to characterize PMR1-mediated mRNA decay in cultured cells. PMR1
      participates in a number of different complexes. We show several approaches for
      studying these complexes, and we describe techniques for isolating and
      characterizing PMR1-interacting proteins and its target mRNAs. Although the
      various techniques described here have proven their usefulness in studying PMR1,
      they can be generalized to studying decay by any other mRNA endonuclease.

PMID- 19111181
TI  - Methods to determine mRNA half-life in Saccharomyces cerevisiae.
AB  - Much of our understanding of eukaryotic mRNA decay has come from studies in
      budding yeast, Saccharomyces cerevisiae. The facile nature of genetic and
      biochemical manipulations in yeast has allowed detailed investigations into the
      mRNA decay pathway and the identification of critical factors required for each
      step. Discussed herein are standard protocols for measuring mRNA half-lives in
      yeast. It should be noted, however, that variations of these assays are possible.
      In addition, a few a priori considerations are addressed.

PMID- 19111182
TI  - mRNA Decay analysis in Drosophila melanogaster drug-induced changes in
      glutathione S-transferase D21 mRNA stability.
AB  - We have established an in vivo system to investigate mechanisms by which
      pentobarbital (PB), a psychoactive drug with a sedative effect, changes the rate
      of decay of gstD21 mRNA (encoding a Drosophila glutathione S-transferase). Here
      we describe methods for the use of hsp70 promoter-based transgenes and transgenic
      lines to determine mRNA half-lives by RNase protection assays in Drosophila. We
      are able to identify and map putative decay intermediates by cRT-PCR and DNA
      sequencing of the resulting clones. Our results indicate that the 3'-UTR of
      gstD21 mRNA is responsive to PB by regulating mRNA decay and that the cis-acting
      element(s) responsible for the PB-mediated stabilization resides in a 59
      nucleotide sequence in the 3'-UTR of the gstD21 mRNA (Akgul and Tu, 2007).

PMID- 19111183
TI  - Measuring mRNA stability during early Drosophila embryogenesis.
AB  - Maternal mRNAs play a major role in directing early Drosophila melanogaster
      development, and thus, precise posttranscriptional regulation of these messages
      is imperative for normal embryogenesis. Although initially abundant on egg
      deposition, a subset of these maternal mRNAs is targeted for destruction during
      the first 2 to 3 h of embryogenesis. In this chapter, we describe molecular
      methods to determine the kinetics and mechanisms of maternal mRNA decay in the
      early D. melanogaster embryo. We show how both unfertilized eggs and fertilized
      embryos can be used to identify maternal mRNAs destined for degradation, to
      explain changes in decay kinetics over time, and to uncover the molecular
      mechanisms of targeted maternal mRNA turnover. In the first section, we explore
      the methods and outcomes of measuring decay on a "gene-by-gene" basis, which
      involves examination of a small number of transcripts by Northern blotting, RNA
      dot blotting, and real-time RT-PCR. In the second section, we provide a
      comprehensive examination of the applications of microarray technology to study
      global changes in maternal mRNA decay during early development. Genome-wide
      surveys of maternal mRNA turnover provide a wealth of information regarding the
      magnitude, temporal regulation, and genetic control of maternal mRNA turnover.
      Methods that permit the collection and analysis of highly reproducible and
      statistically robust data in this developmental system are discussed.

PMID- 19111185
TI  - Trypanosomes as a model to investigate mRNA decay pathways.
AB  - In trypanosomes, individual mRNAs arise by the processing of primary
      polycistronic transcripts. Consequently, mRNA degradation rates are critical
      determinants of mRNA abundance. In this chapter, we summarize the various options
      for genetic manipulation in trypanosomes with the goal of analyzing mRNA
      stability, including RNA interference. We describe a method for measuring the
      half-lives of trypanosome mRNAs, including those that are very unstable, and also
      the isolation of tagged protein-RNA complexes by IgG affinity chromatography.
      Last, we detail our current methods for RNA analysis with microarrays.

PMID- 19111184
TI  - Messenger RNA half-life measurements in mammalian cells.
AB  - The recognition of the importance of mRNA turnover in regulating eukaryotic gene
      expression has mandated the development of reliable, rigorous, and "user
      friendly" methods to accurately measure changes in mRNA stability in mammalian
      cells. Frequently, mRNA stability is studied indirectly by analyzing the steady
      state level of mRNA in the cytoplasm; in this case, changes in mRNA abundance are
      assumed to reflect only mRNA degradation, an assumption that is not always
      correct. Although direct measurements of mRNA decay rate can be performed with
      kinetic labeling techniques and transcriptional inhibitors, these techniques
      often introduce significant changes in cell physiology. Furthermore, many
      critical mechanistic issues as to deadenylation kinetics, decay intermediates,
      and precursor-product relationships cannot be readily addressed by these methods.
      In light of these concerns, we have previously reported transcriptional pulsing
      methods based on the c-fos serum-inducible promoter and the tetracycline
      regulated (Tet-off) promoter systems to better explain mechanisms of mRNA
      turnover in mammalian cells. In this chapter, we describe and discuss in detail
      different protocols that use these two transcriptional pulsing methods. The
      information described here also provides guidelines to help develop optimal
      protocols for studying mammalian mRNA turnover in different cell types under a
      wide range of physiologic conditions.

PMID- 19111186
TI  - Cell type-specific analysis of mRNA synthesis and decay in vivo with uracil
      phosphoribosyltransferase and 4-thiouracil.
AB  - Microarray-based analysis of mRNA expression has provided a genome-wide
      understanding of the genes and pathways involved in many biological processes.
      However, two limitations are often associated with traditional microarray
      experiments. First, standard methods of microarray analysis measure mRNA
      abundance, not mRNA synthesis or mRNA decay, and, therefore, do not provide any
      information regarding the mechanisms regulating transcript levels. Second,
      microarrays are often performed with mRNA from a mixed population of cells, and
      data for a specific cell-type of interest can be difficult to obtain. This
      chapter describes a method, referred to here as "4TU-tagging," which can be used
      to overcome these limitations. 4TU-Tagging uses cell type-specific expression of
      the uracil phosphoribosyltransferase gene of Toxoplasma gondii and the uracil
      analog 4-thiouracil (4TU) to selectively tag and purify RNA. Pulse-labeling of
      newly synthesized RNA with 4TU followed by a "chase" with unmodified uracil
      allows in vivo measurements of mRNA synthesis and decay in specific cells.
      Experimental design considerations for applying 4TU-tagging to different systems
      and protocols for cell type-specific RNA tagging, purification, and microarray
      analysis are covered in this chapter.

PMID- 19111187
TI  - Analysis of cytoplasmic mRNA decay in Saccharomyces cerevisiae.
AB  - The yeast, Saccharomyces cerevisiae, is a model system for the study of
      eukaryotic mRNA degradation. In this organism, a variety of methods have been
      developed to measure mRNA decay rates, trap intermediates in the mRNA degradation
      process, and establish precursor-product relationships. In addition, the use of
      mutant strains lacking specific enzymes involved in mRNA destruction, or key
      regulatory proteins, allows one to determine the mechanisms by which individual
      mRNAs are degraded. In this chapter, we discuss methods for analyzing mRNA
      degradation in S. cerevisiae.

PMID- 19111188
TI  - Transcriptome targets of the exosome complex in plants.
AB  - The exosome complex is endowed with the capabilities to conduct 3'-end RNA
      processing, 3'-end degradation, and surveillance of various RNA substrates.
      Although the exosome is present in both eukaryotes and archaea, where it plays a
      central role in cellular RNA metabolism, a substantial degree of variability
      exists in its modus operandi in the different domains of life. This chapter
      discusses features of the exosome in plants that distinguish it from the exosome
      in archaea, fungi, and animals, as well as reviews the resources and tools that
      are needed to identify and catalog plant exosome targets on a transcriptome-wide
      scale.

PMID- 19111189
TI  - Sensitive detection of mRNA decay products by use of reverse-ligation-mediated
      PCR (RL-PCR).
AB  - Ligation-mediated PCR allows the detection and mapping of cleavage products of
      specific nucleic acid molecules out of complex nucleic acid mixtures. It can be
      applied to the detection of either degradation products of exogenously added
      nucleases in footprinting applications or natural decay products or reaction
      intermediates. We have developed various ligation-mediated PCR approaches to
      analyze mRNAs, all relying on RNA ligation, followed by reverse-transcription and
      PCR amplification. We have termed these approaches reverse-ligation-mediated PCR
      (RL-PCR). The ligation event involves either an RNA linker added to the 5'-end of
      cleaved RNA or RNA circularization, allowing, respectively, the mapping and
      quantification of the cleavage points or the simultaneous analysis of the
      presence or absence of the 5'-cap structure and the length of the poly(A) tail.
      These methods enabled us to develop a very efficient 5'-RACE procedure to map
      mRNA 5'-ends, to footprint in permeabilized cells the interaction of regulatory
      proteins with RNA, to detect the products of cellular ribozyme action and to
      analyze cellular decay pathways that involve deadenylation and/or decapping. I
      review herein the methodologic aspects and protocols of the various RL-PCR
      procedures we have developed.

PMID- 19111190
TI  - Tethering assays to investigate nonsense-mediated mRNA decay activating proteins.
AB  - Nonsense-mediated mRNA decay (NMD) is activated by exon-junction complexes (EJCs)
      that are located downstream of the termination codon of the substrate mRNAs. This
      situation can be imitated by tethering components of the EJC to the 3'
      untranslated region (3' UTR) of a reporter mRNA. Here we describe the detailed
      use of two analogous tethering systems that are based on the coat protein of
      bacteriophage MS2 or on the 22 amino acid RNA-binding domain of the bacteriophage
      lambda-antiterminator protein N (lambdaN-peptide). These polypeptides are fused
      as tags to proteins of interest. Their respective RNA binding sites are inserted
      into reporter mRNAs. This enables recruitment of the NMD activity of the fusion
      protein to an NMD-activating position, bypassing the requirement for splicing. In
      this chapter we explicate the cloning of appropriate reporter plasmids and the
      setup of a tethering experiment with the necessary control experiments.
      Advantages of the different systems and tags are discussed.

PMID- 19111191
TI  - Assays for determining poly(A) tail length and the polarity of mRNA decay in
      mammalian cells.
AB  - This chapter describes several methods for measuring the length of the mRNA
      poly(A) tail and a novel method for measuring mRNA decay. Three methods for
      measuring the length of a poly(A) tail are presented: the poly(A) length assay,
      the ligation-mediated poly(A) test (LM-PAT), and the RNase H assay. The first two
      methods are PCR-based assays involving cDNA synthesis from an oligo(dT) primer.
      The third method involves removing the poly(A) tail from the mRNA of interest. A
      major obstacle to studying the enzymatic step of mammalian mRNA decay has been
      the inability to capture mRNA decay intermediates with structural impediments
      such as the poly(G) tract used in yeast. To overcome this, we combined a standard
      kinetic analysis of mRNA decay with a tetracycline repressor-controlled reporter
      with an Invader RNA assay. The Invader RNA assay is a simple, elegant assay for
      the quantification of mRNA. It is based on signal amplification, not target
      amplification, so it is less prone to artifacts than other methods for nucleic
      acid quantification. It is also very sensitive, able to detect attomolar levels
      of target mRNA. Finally, it requires only a short sequence for target recognition
      and quantitation. Therefore, it can be applied to determining the decay polarity
      of a mRNA by measuring the decay rates of different portions of that mRNA.

PMID- 19111192
TI  - Analyzing P-bodies in Saccharomyces cerevisiae.
AB  - Cytoplasmic processing bodies, or P-bodies, are RNA-protein granules found in
      eukaryotic cells. P-bodies contain non-translating mRNAs and proteins involved in
      mRNA degradation and translational repression. P-bodies, and the mRNPs within
      them, have been implicated in mRNA storage, mRNA degradation, and translational
      repression. The analysis of mRNA turnover often involves the analysis of P
      bodies. In this chapter, we describe methods to analyze P-bodies in the budding
      yeast, Saccharomyces cerevisiae, including procedures to determine whether a
      protein or mRNA can accumulate in P-bodies, whether an environmental perturbation
      or mutation affects P-body size and number, and methods to quantify P-bodies.

PMID- 19111193
TI  - Real-time and quantitative imaging of mammalian stress granules and processing
      bodies.
AB  - Nuclear mRNA domains such as nucleoli, speckles, Cajal bodies, and gems
      demonstrate that RNA function and morphology are inextricably linked; granular
      mRNA structures are self-generated in tandem with metabolic activity. Similarly,
      cytoplasmic compartmentalization of mRNA into mRNP structures such as stress
      granules (SGs) and processing bodies (PBs) reiterate the link between function
      and structure; the assembly of SGs and PBs requires mRNA released from
      disassembling polysomes on translational arrest. SGs contain mRNA still
      associated with some of the translational machinery, specifically 40S subunits
      and a subset of translation initiation factors including eIF3, eIF4F, eIF4B, and
      PABP. PBs also contain mRNA and eIF4E but lack other preinitiation factors and
      contain instead a number of proteins associated with mRNA decay such as DCP1a,
      DCP2, hedls/GE-1, p54/RCK. Many other proteins (e.g., argonaute, FAST, RAP-55,
      TTP) and microRNAs are present in both SGs and PBs, sometimes shepherding
      specific mRNA transcripts between the translation and decay machineries.
      Recently, we described markers and methods to visualize SGs and PBs in fixed
      cells (Kedersha and Anderson, 2007), but understanding the dynamic nature of SGs
      and PBs requires live cell imaging. This presents unique challenges, because it
      requires the overexpression of fluorescently tagged SG/PB marker proteins, which
      can shift the mRNA equilibrium toward SGs or PBs, thus obscuring the result. We
      describe stably expressed, fluorescently tagged SG and PB markers that exhibit
      similar behavior to their endogenous counterparts, thus allowing real-time
      imaging of SGs and PBs.

PMID- 19111195
TI  - The National Report Card on the State of Emergency Medicine: evaluating the
      emergency care environment state by state 2009 edition.

PMID- 19111194
TI  - Cell biology of mRNA decay.
AB  - Studying single mRNA molecules has added new dimensions to our understanding of
      gene expression and the life cycle of mRNA in cells. Advances in microscopes and
      detection technology have opened access to single molecule research to most
      researchers interested in molecular biology. Here we provide an overview
      technique for single molecule studies of RNA in either fixed samples or in living
      cells. As part of a volume on mRNA turnover, it is increasingly relevant, because
      many of the recent advances in studies of mRNA turnover have suggested that there
      is non-homogeneous distribution of turnover factors in the cell. For this reason,
      understanding of spatial relationships between mRNA and mRNA turnover factors
      should enrich our understanding of this process.

PMID- 19111196
TI  - Annals of Emergency Medicine Journal Club. The National Report Card on the State
      of Emergency Medicine: evaluating the emergency care environment state by state
      2009 edition.

PMID- 19111198
TI  - "How's work?".

PMID- 19111199
TI  - Male with pain in left hand.

PMID- 19111200
TI  - Male with torso injury.

PMID- 19111201
TI  - Sensitivity of computed tomography for subarachnoid hemorrhage.

PMID- 19111202
TI  - The answer to imperfect computed tomography sensitivity for subarachnoid
      hemorrhage: use clinical judgment.

PMID- 19111204
TI  - Remifentanil for procedural sedation in the emergency department.

PMID- 19111205
TI  - Clinical judgment, clinical decision rules, and evidence-based medicine: thoughts
      on "an observation of failure to validate the San Francisco Syncope Rule".

PMID- 19111206
TI  - United States Renal Data System 2008 Annual Data Report.

PMID- 19111211
TI  - Two on the fast track: arthroscopic rotator cuff repair and subacromial
      decompression with coracoacromial ligament excision.

PMID- 19111212
TI  - Single-row versus double-row arthroscopic rotator cuff repair: a prospective
      randomized clinical study.
AB  - PURPOSE: The purpose of this study was to compare the clinical outcome of
      arthroscopic rotator cuff repair with single-row and double-row techniques.
      METHODS: Eighty patients with a full-thickness rotator cuff tear underwent
      arthroscopic repair with suture anchors. They were divided into 2 groups of 40
      patients according to repair technique: single row (group 1) or double row (group
      2). Results were evaluated by use of the Disabilities of the Arm, Shoulder and
      Hand (DASH) and Work-DASH self-administered questionnaires, normalized Constant
      score, and muscle strength measurement. On analyzing the results at a 2-year
      follow-up, we considered the following independent variables: baseline scores;
      age; gender; dominance; location, shape, and area of cuff tear; tendon
      retraction; fatty degeneration; treatment of biceps tendon; and rotator cuff
      repair technique (anchors or anchors and side to side). Univariate and
      multivariate statistical analyses were performed to determine which variables
      were independently associated with the outcome. Significance was set at P < .05.
      RESULTS: Of the patients, 8 (10%) were lost to follow-up. Comparison between
      groups did not show significant differences for each variable considered.
      Overall, according to the results, the mean DASH scores were 15.4 +/- 15.6 points
      in group 1 and 12.7 +/- 10.1 points in group 2; the mean Work-DASH scores were
      16.0 +/- 22.0 points and 9.6 +/- 13.3 points, respectively; and the mean Constant
      scores were 100.5 +/- 17.8 points and 104.9 +/- 21.8 points, respectively. Muscle
      strength was 12.7 +/- 5.7 lb in group 1 and 12.9 +/- 7.0 lb in group 2.
      Univariate and multivariate analysis showed that only age, gender, and baseline
      strength significantly and independently influenced the outcome. Differences
      between groups 1 and 2 were not significant. CONCLUSIONS: At short-term follow
      up, arthroscopic rotator cuff repair with the double-row technique showed no
      significant difference in clinical outcome compared with single-row repair. LEVEL
      OF EVIDENCE: Level I, high-quality randomized controlled trial with no
      statistically significant differences but narrow confidence intervals.

PMID- 19111213
TI  - The effect of coracoacromial ligament excision and acromioplasty on superior and
      anterosuperior glenohumeral stability.
AB  - PURPOSE: To determine the effect of coracoacromial ligament (CAL) resection and
      subacromial decompression (SAD)/acromioplasty on humeral head translation under
      anterosuperior and superior loading in a cadaveric model with an intact rotator
      cuff. METHODS: Six cadaveric shoulders were tested in the intact state, following
      CAL resection and following SAD. RESULTS: Excision of the CAL led to a
      significant increase in anterosuperior humeral translation of 2.1 mm (17%). SAD
      led to a significant increase in superior humeral translation of 2.5 mm (28%).
      CONCLUSIONS: The results of this cadaveric study showed that resection of the CAL
      led to a 2.1-mm increase in anterosuperior translation and that SAD led to a 2.5
      mm increase in superior translation. CLINICAL RELEVANCE: CAL resection and SAD
      are common surgical procedures, which may lead to increases in anterosuperior and
      superior glenohumeral instability.

PMID- 19111214
TI  - Posterior arthroscopic capsular release in frozen shoulder.
AB  - PURPOSE: The aims of our study were to assess the overall effectiveness of
      arthroscopic capsular release and to determine if the addition of a posterior
      capsular release had any benefit, particularly in relation to internal rotation.
      METHODS: Forty-eight consecutive patients with primary or secondary frozen
      shoulder in whom conservative physiotherapy had failed were included in the
      study. Arthroscopic capsular release was performed in all cases. Group 1 had an
      anterior and inferior release only; group 2 included a posterior release. All
      data were collected prospectively. Constant-Murley functional scores were used to
      assess outcome. Overall satisfaction and patient reported outcomes were also
      measured. RESULTS: The mean patient age was 51 years (range, 28 to 65 years),
      with no difference between the 2 groups. There were 27 patients in group 1 and 21
      patients in group 2. The mean follow-up was 5 months. Etiology of the frozen
      shoulder was primary (22), diabetic (7), post-traumatic (7), and postoperative
      (11). Overall across both groups, there was a highly significant improvement in
      Constant score (P < .001) postoperatively. A similar pattern was noted in the
      range of motion (P < .001). The mean satisfaction score was 7 of 10
      postoperatively. The patients reported overall outcome as much better (24),
      better (15), the same (1), and worse (4). There was no significant difference in
      Constant score between the 2 groups, and no significant difference in the
      improvement of the range of motion, in particular internal rotation. CONCLUSIONS:
      We have shown an overall rapid significant improvement following arthroscopic
      capsular release for primary and secondary frozen shoulder. There was no
      significant difference in the overall outcome with the addition of a posterior
      release. LEVEL OF EVIDENCE: Level III, therapeutic, retrospective comparative
      study.

PMID- 19111215
TI  - Comparative study of the influence of room-temperature and warmed fluid
      irrigation on body temperature in arthroscopic shoulder surgery.
AB  - PURPOSE: The purpose of this study was to evaluate the effect of irrigation fluid
      temperature on body temperature and other variables, and to determine their
      correlations. METHODS: A prospective randomized study was performed of 50
      patients undergoing arthroscopic shoulder surgery who received irrigation fluid
      either with room temperature or warmed to 37 degrees C to 39 degrees C. Core body
      temperature was checked at regular intervals, and additional variables, such as
      length of anesthesia and surgery, amount of irrigation fluid and intravenous
      fluid used, amount of bleeding, weight gain, and postoperative pain were
      collected during surgery and postoperatively. RESULTS: The final core body
      temperature was 35.5 +/- 0.3 degrees C in the room-temperature fluid group and
      36.2 +/- 0.3 degrees C in the warmed fluid group (P < .001). The temperature drop
      was 0.86 +/- 0.2 degrees C in the room-temperature fluid group and 0.28 +/- 0.2
      degrees C in the warmed fluid group (P < .001). Hypothermia occurred in 91.3% of
      patients in the room-temperature fluid group; the incidence of hypothermia was
      much lower in the warmed fluid group (17.4%; P < .001). Of the variables
      measured, the patient's age and amount of irrigation fluid used correlated with
      core body temperature in the room-temperature fluid group. No variables
      correlated with core body temperature in the warmed fluid group. CONCLUSIONS:
      Hypothermia occurred more often in shoulder arthroscopic surgery with room
      temperature fluid irrigation than with warmed fluid irrigation. The patient's age
      and amount of irrigation fluid used correlate with core body temperature when
      using room-temperature irrigation fluid. The use of warm irrigation fluid during
      arthroscopic shoulder surgery decreases perioperative hypothermia, especially in
      elderly patients. LEVEL OF EVIDENCE: Level I, therapeutic randomized controlled
      trial.

PMID- 19111216
TI  - Prognostic factors affecting anatomic outcome of rotator cuff repair and
      correlation with functional outcome.
AB  - PURPOSE: To analyze the relationship between functional outcomes and
      postoperative cuff integrity (anatomic outcome), and to reveal the factors
      affecting outcomes of rotator cuff repair. METHODS: Seventy-eight patients who
      had undergone repair of full-thickness rotator cuff tear received both computed
      tomographic arthrography (CTA) and functional evaluation a minimum of 1 year
      after surgery. The mean follow-up period was 19.6 months (range, 12 to 39
      months). Anatomic outcome was evaluated by CTA. Functional outcomes were
      evaluated by visual analogue scale (VAS) for pain and satisfaction with the
      operation, Constant score, simple shoulder test (SST), and American Shoulder and
      Elbow Surgeons (ASES) score. Various clinical and structural factors were
      included for statistical analysis. RESULTS: All patients displayed significant
      improvement in all functional evaluations at the final visit. Functional outcome
      did not correlate with anatomic outcome (P > .05). A few variables did relate to
      functional outcome: female or old age statistically correlated with the score of
      SST, and the size of the tear correlated with the ASES score (P < .05). The
      retear was influenced by age, fatty degeneration of the cuff muscles, and the
      size of tear. Fatty degeneration of the infraspinatus was the most independent
      predictor of anatomic outcome on multivariate regression analysis. CONCLUSIONS:
      Rotator cuff repair brought significant functional improvement. However, the
      functional outcome did not correlate with the anatomic outcome. The fatty
      degeneration of the infraspinatus muscle served as an independent predictor of
      the postoperative integrity of the rotator cuff. LEVEL OF EVIDENCE: Level IV,
      prognostic case series.

PMID- 19111218
TI  - Medial opening wedge high tibial osteotomy with early full weight bearing.
AB  - PURPOSE: We performed clinical and radiographic evaluation of patients with
      medial compartment osteoarthritis of the knee who had undergone treatment with
      opening wedge high tibial osteotomy (OWHTO) followed by early full weight
      bearing. OWHTO procedures were performed by use of TomoFix (Synthes, Bettlach,
      Switzerland) and bone substitute materials. METHODS: OWHTO was performed in 57
      knees in 52 patients with a mean age of 69 years (range, 54 to 82 years) at the
      time of operation. The diagnosis was primary osteoarthritis in 34 knees in 29
      patients and osteonecrosis in a further 23 knees in 23 patients. We established
      an early weight-bearing exercise program during which these patients were
      permitted partial weight-bearing exercise 1 week after their osteotomy procedure.
      All patients performed full weight-bearing exercises at 2 weeks after surgery.
      The mean follow-up period was 40 months (range, 24 to 62 months). RESULTS: The
      American Knee Society Score and Function Score showed significant improvement
      from 50.9 +/- 12.3 to 91.7 +/- 6.9 points and 59.3 +/- 13.1 to 94.1 +/- 8.8
      points, respectively. Before surgery, the mean femorotibial angle during standing
      was 181.3 degrees +/- 2.4 degrees (1.3 degrees anatomic varus), but it measured
      169.6 degrees +/- 2.3 degrees (10.4 degrees valgus) at the time of follow-up.
      There were no instances of nonunion or implant failure in any of our patients.
      CONCLUSIONS: We have shown that an early weight-bearing exercise program enables
      full weight bearing at 2 weeks after OWHTO with TomoFix and artificial bone
      wedges. Overall, this combination was a highly successful course of treatment for
      correcting knee malalignment in patients with medial compartment osteoarthritis.
      LEVEL OF EVIDENCE: Level IV, therapeutic case series.

PMID- 19111217
TI  - Scapular dyskinesis and SICK scapula syndrome in patients with chronic type III
      acromioclavicular dislocation.
AB  - PURPOSE: This study was aimed at evaluating whether scapular dyskinesis and,
      eventually, SICK (Scapular malposition, Inferior medial border prominence,
      Coracoid pain and malposition, and dysKinesis of scapular movement) scapula
      syndrome develop in patients with chronic type III acromioclavicular (AC)
      dislocation. METHODS: Scapulothoracic motion was studied in 34 patients with
      chronic AC dislocation by use of the protocol described by Kibler et al. and
      Burkhart et al. An anteroposterior radiograph of the scapulae with the arms
      abducted was also obtained. The SICK Scapula Rating Scale was applied to patients
      with SICK scapula syndrome. Shoulder function was assessed with the Constant
      score and Simple Shoulder Test (SST). RESULTS: Of the 34 patients, 24 (70.6%) had
      scapular dyskinesis with the arms at rest, and 14 of these (58.3%) had SICK
      scapula syndrome. The mean SICK Scapula Rating Scale score was 6.9 points (out of
      a possible 20 points). Clinical and radiographic evaluations with the arms
      abducted at 90 degrees confirmed scapular dyskinesis in 61.7% and 64.7% of
      patients, respectively (P > .05). The Constant score was 83 points for the
      pathologic side and 91 points for the contralateral side. The Constant score
      value was 75 and 88, respectively, in patients with dyskinesis and those without
      dyskinesis (P < .05); the mean value for the SST was 8 of 12 and 10 of 12,
      respectively. CONCLUSIONS: Chronic type III AC dislocation causes scapular
      dyskinesis in 70.6% of patients. Of the latter, 58.3% have SICK scapula syndrome
      develop. Dyskinesis might be due to loss of the stable fulcrum of the shoulder
      girdle represented by the AC joint and due to the superior shoulder pain caused
      by the dislocation. The values for the Constant score and SST were lower in
      patients with dyskinesis. LEVEL OF EVIDENCE: Level IV, prognostic case series.

PMID- 19111219
TI  - Improved divergence angles with femoral interference screw placement through the
      tibial tunnel as measured by multiplanar reconstruction computed tomography.
AB  - PURPOSE: A modified technique for anterior cruciate ligament (ACL) reconstruction
      without graft injury by femoral interference screw insertion directly through the
      tibial tunnel is reported. This study evaluated femur bioabsorbable interference
      screw divergence and obliquity of the graft and tunnel positions as measured by
      multiplanar reconstruction computed tomography (MPR-CT) after endoscopic ACL
      reconstruction. METHODS: Twenty-five patients who underwent single-incision
      arthroscopically assisted ACL reconstruction using hamstring tendon autografts
      were enrolled in this prospective study. All procedures were performed using the
      same technique: femoral bioabsorbable interference screw insertion directly
      through the tibial tunnel. Divergence angles of oblique sagittal and oblique
      axial views of the graft and tunnel positions using MPR-CT evaluation were
      obtained. CT images were evaluated in a blinded manner by 3 experienced
      radiologists. RESULTS: The average divergence angles in oblique sagittal and
      oblique axial views were 0.88 +/- 1.06 and 1.44 +/- 1.17, respectively. Sagittal,
      axial, and coronal obliquity of the graft in reconstructed patients averaged 64
      degrees (range, 46 degrees to 69 degrees ), 19 degrees (range, 17 degrees to 22.5
      degrees ), and 73.6 degrees (range, 70 degrees to 77.6 degrees ), respectively.
      Radiologic analysis of the femoral insertion according to the quadrant technique
      showed that the femoral center of the anteromedial (grafted) bundle was 18.6% and
      23.6% of the depth of Blumensaat's line and the height of the femoral condyle. At
      the tibia, the tibial ACL attachment at the center of the anteromedial bundle was
      at 41.1% of the maximal tibial diameter. CONCLUSIONS: Our study showed that MPR
      CT is a useful diagnostic tool for evaluation of the femoral interference screw
      divergence, obliquity of the graft, and the exact femoral and tibial insertion
      site of the graft. The screw will have little or no divergence using this novel
      technique as measured by the very accurate MPR-CT. LEVEL OF EVIDENCE: Level IV,
      therapeutic case series.

PMID- 19111220
TI  - Tibiofemoral joint contact area and pressure after single- and double-bundle
      anterior cruciate ligament reconstruction.
AB  - PURPOSE: The purpose of this study was to compare the tibiofemoral contact area
      and pressure after single-bundle (SB) and double-bundle (DB) anterior cruciate
      ligament (ACL) reconstruction by use of 2 femoral and 2 tibial tunnels in intact
      cadaveric knees. METHODS: Tibiofemoral contact area and mean and maximum
      pressures were measured by pressure-sensitive film (Fujifilm, Valhalla, NY)
      inserted between the tibia and femur. The knee was subjected to a 1,000-N axial
      load by use of a uniaxial testing machine at 0 degrees , 15 degrees , 30 degrees
      , and 45 degrees of flexion. Three conditions were evaluated: (1) intact ACL, (2)
      SB ACL reconstruction (n = 10 knees), and (3) DB ACL reconstruction (n = 9
      knees). RESULTS: When compared with the intact knee, DB ACL reconstruction showed
      no significant difference in tibiofemoral contact area and mean and maximum
      pressures. SB ACL reconstruction had a significantly smaller contact area on the
      lateral and medial tibiofemoral joints at 30 degrees and 15 degrees of flexion.
      SB ACL reconstruction also had significantly higher mean pressures at 15 degrees
      of flexion on the medial tibiofemoral joint and at 0 degrees and 15 degrees of
      flexion on the lateral tibiofemoral joint, as well as significantly higher
      maximum pressures at 15 degrees of flexion on the lateral tibiofemoral joint.
      CONCLUSIONS: SB ACL reconstruction resulted in a significantly smaller
      tibiofemoral contact area and higher pressures. DB ACL more closely restores the
      normal contact area and pressure mainly at low flexion angles. CLINICAL
      RELEVANCE: Our findings suggest that the changes in the contact area and
      pressures after SB ACL reconstruction may be one of the causes of osteoarthritis
      on long-term follow-up. DB ACL reconstruction may reduce the incidence of
      osteoarthritis by closely restoring contact area and pressure.

PMID- 19111221
TI  - Comparison of single- and double-bundle anterior cruciate ligament reconstruction
      using quadriceps tendon-bone autografts.
AB  - PURPOSE: The purpose of this study was to evaluate and compare postoperative knee
      stability and functional scores between single- and double- bundle anterior
      cruciate ligament (ACL) reconstruction with the use of quadriceps tendon-bone
      autografts at a 2-year follow-up. METHODS: The records of 59 patients who had ACL
      reconstruction between January 2005 and April 2006 were analyzed retrospectively.
      Twenty-eight patients had single-bundle reconstruction (group S) and 31 received
      double-bundle reconstruction (group D). Ligament stability was assessed with the
      Lachman and pivot-shift tests and a KT-2000 arthrometer. International Knee
      Documentation Committee (IKDC) and Lysholm scores were employed to evaluate the
      functional outcomes. RESULTS: The postoperative mean side-to-side difference for
      group S was 2.64 mm and 1.79 mm for group D, a difference that was found to be
      statistically significant (P = .020). Regarding the pivot-shift test, 3 patients
      had grade 1+ and 1 patient had grade 2+ pivot-shift in group S, while no patients
      had abnormal pivot-shift in group D (P = .093). The patients who reported grade A
      or B on IKDC scores were 24 and 28 in group S and D, respectively (P > .1). On
      the questionnaire of the twisting activity, although statistical difference was
      not found between the groups, there was a trend toward more restriction in
      twisting activity in group S (P = .096). We found significant correlation between
      the twisting activity and instability questionnaire of the Lysholm score
      (Spearman coefficient, 0.737; P < .001). CONCLUSIONS: Double-bundle ACL
      reconstruction using quadriceps tendon-bone autografts provide less laxity (1.79
      mm) than single-bundle ACL reconstruction (2.64 mm) as measured by the KT-2000.
      However, we could not find any significant differences in the functional
      measurements between the 2 groups. LEVEL OF EVIDENCE: Level III, retrospective
      comparative study.

PMID- 19111222
TI  - Single-tunnel suture fixation of posterior cruciate ligament avulsion fracture.
AB  - PURPOSE: The purpose of this study was to evaluate the clinical results of
      arthroscopic treatment of tibial avulsion fracture of the posterior cruciate
      ligament (PCL) by suture fixation technique through a single bone tunnel.
      METHODS: We arthroscopically treated 28 patients (mean age, 35.3 years) with PCL
      avulsion fractures using 2 posteromedial portals. The bony fragment was sutured
      by use of a suture hook and was then reduced into the top of the tibial bone
      tunnel created from the anterior tibial cortex to the bottom of the fracture bed.
      Slight depression of 1 to 3 mm of the osseous fragment was achieved. We followed
      up 24 cases for more than 2 years. RESULTS: The fracture usually healed at 6 to
      12 weeks (mean, 2.8 months) after surgery. At the last follow-up, all patients
      achieved normal range of motion of the knees, except for 2 patients who had 5
      degrees and 10 degrees terminal flexion limitations of the involved knees,
      respectively. KT-1000 examination (MEDmetric, San Diego, CA) showed that the side
      to-side difference was 0 to 2 mm in 23 patients and 3 mm in 1 patient, with a
      mean of 0.7 +/- 0.8 mm. The Lysholm score was 92 to 100, with a mean of 95.2 +/-
      2.3. On the basis of the International Knee Documentation Committee knee
      examination form, the results were graded as normal in 20 patients and as nearly
      normal in the other 4. The mean Tegner score was 6.8 +/- 0.4 preoperatively and
      6.6 +/- 0.5 at the last follow-up (P = .23). CONCLUSIONS: The single-tibial
      tunnel technique seemed not only to simplify the procedure but also to facilitate
      slight depression of the bony fragment, which might have been useful to restore
      normal tension of the PCL. Clinically, this technique was reproducible and
      effective. LEVEL OF EVIDENCE: Level IV, therapeutic case series.

PMID- 19111223
TI  - A review of evidence-based medicine for glucosamine and chondroitin sulfate use
      in knee osteoarthritis.
AB  - The investigation of disease-modifying treatment options for osteoarthritis (OA)
      has become an important aspect of orthopaedic care. The purpose of this review is
      to critically evaluate the evidence for the use of glucosamine and chondroitin
      sulfate for knee OA with the goal of elucidating their indications for clinical
      use. The published clinical studies of glucosamine and chondroitin sulfate on OA
      are reviewed within the context of evidence-based medicine. Almost every included
      trial has found the safety of these compounds to be equal to placebo. In the
      literature satisfying our inclusion criteria, glucosamine sulfate, glucosamine
      hydrochloride, and chondroitin sulfate have individually shown inconsistent
      efficacy in decreasing OA pain and improving joint function. Many studies
      confirmed OA pain relief with glucosamine and chondroitin sulfate use. The
      excellent safety profile of glucosamine and chondroitin sulfate therapy should be
      discussed with patients, and these supplements may serve a role as an initial
      treatment modality for many OA patients.

PMID- 19111224
TI  - Anteromedial portal technique for the anterior cruciate ligament femoral socket:
      pitfalls and solutions.
AB  - Creating the anterior cruciate ligament (ACL) femoral socket using the
      anteromedial (AM) portal technique has advantages. Furthermore, the technique is
      ideal for anatomic double-bundle (particularly posterolateral bundle) and all
      inside ACL techniques. However, although the AM portal technique has advantages,
      the learning curve is steep when making the transition from familiar, transtibial
      reaming to the AM portal technique for ACL femoral tunnel creation. Complications
      and challenges are many when learning the AM portal technique. The purpose of
      this technical note is to describe tips and pearls for surgeons contemplating the
      transition to the AM portal technique for the ACL femoral socket.

PMID- 19111225
TI  - The "bony Bankart bridge" procedure: a new arthroscopic technique for reduction
      and internal fixation of a bony Bankart lesion.
AB  - Arthroscopic treatment of bony Bankart lesions can be challenging. We present a
      new easy and reproducible technique for arthroscopic reduction and suture anchor
      fixation of bony Bankart fragments. A suture anchor is placed medially to the
      fracture on the glenoid neck, and its sutures are passed around the bony fragment
      through the soft tissue including the inferior glenohumeral ligament complex. The
      sutures of this anchor are loaded in a second anchor that is placed on the
      glenoid face. This creates a nontilting 2-point fixation that compresses the
      fragment into its bed. By use of the standard technique, additional suture
      anchors are used superiorly and inferiorly to the bony Bankart piece to repair
      the labrum and shift the joint capsule. We call this the "bony Bankart bridge"
      procedure.

PMID- 19111226
TI  - Monoarthritis of the knee with unusual lesions in adults associated with
      varicella-zoster virus infection.
AB  - Varicella-zoster virus-associated arthritis has not been well documented in
      adults. We present the case of a 27-year-old female patient with monoarthritis of
      the knee associated with clinical symptoms typical of varicella. Arthroscopic
      examination showed unusual oval and circular lesions in cartilage, some of which
      measured 5 +/- 3 mm in diameter in weight-supporting zones. Such lesions have not
      been described previously and were type III-A lesions on the Noyes scale or grade
      IV on the Outerbridge scale. On microscopic observation, synovial fluid cultures
      and hemocultures were negative for the presence of bacteria. A biopsy sample and
      synovial liquid from the affected knee produced a positive polymerase chain
      reaction for varicella-zoster virus, genotype E. These findings suggest a strong
      relation between clinical varicella infection and important lesion invasion in
      the knee articulation of such a young adult, probably related to the virus.
      However, it remains necessary to corroborate this relation between cartilage
      destruction and clinical symptoms of varicella associated with monoarthritis of
      an adult knee. Nevertheless, it is advisable to initiate the appropriate
      antiviral treatment in adults with varicella-related gonalgia because the lesions
      produce the most severe effects on exposure to the knee bone.

PMID- 19111227
TI  - The use of rotator interval closure in the arthroscopic treatment of posterior
      shoulder instability.

PMID- 19111229
TI  - Accidental intrathecal sufentanil overdose during combined spinal-epidural
      analgesia for labor.
AB  - A laboring woman was accidentally given 45 microg of sufentanil intrathecally in
      the course of combined spinal-epidural analgesia. She experienced intense
      pruritus and transient swallowing difficulty without respiratory depression, but
      still had incomplete pain relief, with delivery and episiotomy repair requiring
      additional analgesia. This case highlights the importance of adding local
      anesthetic to intrathecal opioids to facilitate effective analgesia during the
      second stage of labor. The contributory systems issues and multiple factors that
      allowed this error to occur are examined.

PMID- 19111230
TI  - Pulseless electrical activity during caesarean delivery under spinal anaesthesia:
      a case report of severe anaphylactic reaction to Syntocinon.
AB  - Anaphylactoid reaction to Syntocinon is rare, but has been described in the
      literature. The reactions described include patchy erythema, hypotension,
      bronchospasm and oxygen desaturation, but pulseless electrical activity following
      Syntocinon has not been reported. We present the case of a 34-year-old
      primigravida with essential hypertension, gestational diabetes and hypothyroidism
      with a twin pregnancy following in vitro fertilization. During elective caesarean
      delivery she developed a severe anaphylactic reaction to Syntocinon leading to
      pulseless electrical activity.

PMID- 19111232
TI  - Vaginal twin delivery: a survey and review of location, anesthesia coverage and
      interventions.

PMID- 19111234
TI  - Bilateral seminal vesicle abscesses.

PMID- 19111235
TI  - An unusual cause of pyonephrosis and intra-peritoneal abscess: ureteral
      urothelial carcinoma.

PMID- 19111236
TI  - UK pricing breakthrough lessens strangle-hold on health-care budgets.

PMID- 19111237
TI  - Opportunities for better cancer outcomes missed in UK primary care.

PMID- 19111238
TI  - Sorafenib for liver cancer: the horizon broadens.

PMID- 19111239
TI  - Liver-cell cancer and transplantation.

PMID- 19111240
TI  - Laparoscopic colectomy: lessons learned and future prospects.

PMID- 19111241
TI  - Radiotherapy in Russia: a redundant method.

PMID- 19111242
TI  - Removal of basal-cell carcinoma of the face.

PMID- 19111245
TI  - Concurrent hormone and radiation therapy in patients with breast cancer: what is
      the rationale?
AB  - Endocrine therapy is often given together with postoperative radiotherapy in
      patients with breast cancer and positive hormone-receptor status. However, few
      experimental or clinical studies address the combined effects of hormone and
      radiation therapy. Preclinical models have shown changes in tumour cell kinetics
      with the addition of tamoxifen, and some show reduced tumour cell death with
      concurrent anti-oestrogen treatment and radiotherapy. Although data from in-vitro
      studies support the notion of antagonistic effects of concurrent tamoxifen and
      radiotherapy on tumour cells, in-vivo research suggests a synergistic effect that
      could be attributable to micro-environmental changes in tumour responsiveness to
      ionising radiation and hormone therapy. Retrospective studies suggest that in
      practical application, concurrent administration of tamoxifen with radiotherapy
      does not compromise local control but might increase toxicity. Preliminary
      results from simultaneous treatment with aromatase inhibitors and radiation
      indicate that this combination of endocrine and radiation therapy could enhance
      cytotoxicity and improve tumour response. Further studies are needed to clarify
      the physiological mechanisms activated by oestrogens, which will allow a more
      thorough understanding of the complex interactions between 17beta-oestradiol and
      P53/P21(WAF1/CIP1)/Rb pathways and of the interaction between endocrine therapy
      and radiotherapy.

PMID- 19111246
TI  - Anti-HIV drugs for cancer therapeutics: back to the future?
AB  - The use of anti-HIV drugs as cancer treatments is not new. Azidothymidine was
      studied as an antineoplastic in the 1990s, but despite promising in vitro data,
      clinical trials showed little antitumour activity. HIV protease inhibitors were
      developed in the early 1990s, and their subsequent incorporation into highly
      active antiretroviral therapy (HAART) has profoundly changed the natural history
      of HIV infection. The potential antitumour properties of these drugs have been
      investigated because of their success in treating HIV-related Kaposi's sarcoma.
      HAART's effects on Kaposi's sarcoma did not always correlate with immune
      reconstitution, and activity against other solid and haematological malignancies
      has been established. Inhibition of tumour-cell invasion and angiogenesis were
      properties first ascribed to inhibition of HIV protease; however, they have
      pleiotropic antitumour effects, including inhibition of inflammatory cytokine
      production, proteasome activity, cell proliferation and survival, and induction
      of apoptosis. HIV protease inhibitors are thus a new class of anticancer drugs
      with multiple effects, and other anti-HIV drugs might hold similar promise.

PMID- 19111247
TI  - Peritoneal minimal residual disease in colorectal cancer: mechanisms, prevention,
      and treatment.
AB  - Roughly one in five patients with colorectal cancer develops peritoneal minimal
      residual disease after surgical resection, and about one in seven patients
      develops peritoneal carcinomatosis. By contrast with the vast body of research
      addressing haematogenous metastasis, little is known about the biology of
      peritoneal spread of colorectal cancer. The development of peritoneal
      carcinomatosis involves well-defined steps including cell shedding and transport,
      adhesion to the mesothelial layer, invasion of and proliferation into the
      submesothelial stroma, and potential access to the systemic circulation. In this
      Review, we summarise the molecular mechanisms and potential preventive measures
      associated with each step of the peritoneal metastatic cascade.

PMID- 19111248
TI  - Effects of comorbidity on screening and early diagnosis of cancer in elderly
      people.
AB  - There is currently little data showing that older adults can derive benefit from
      cancer screening. Advancing age is associated with an increasing prevalence of
      cancer and other chronic conditions, or comorbidity, and questions remain about
      the interactions between comorbidity and cancer screening in the elderly
      population. In this Review, we assess the available evidence on the effects of
      comorbidity on cancer screening in elderly individuals. In view of the high
      heterogeneity of existing data, consistent recommendations cannot be made.
      Decisions on cancer screening in older adults should be based on an appropriate
      assessment of each individual's health status and life expectancy, the benefits
      and harms of screening procedures, and patient preferences. We suggest that
      Comprehensive Geriatric Assessment might be a necessary step to identify
      candidates for cancer screening in the elderly population. Specific clinical
      trials should be done to improve the evidence and show the effectiveness and cost
      effectiveness of cancer screening in older adults.

PMID- 19111250
TI  - A humble chicken virus that changed biology and medicine.

PMID- 19111249
TI  - New-onset diabetes: a potential clue to the early diagnosis of pancreatic cancer.
AB  - Pancreatic cancer has a dismal prognosis because cancer-specific symptoms occur
      only at an advanced stage. If the cancer is to be discovered early, screening
      will need to be done in asymptomatic individuals. Because the incidence of
      pancreatic cancer is low, screening for asymptomatic cancer in the general
      population is not feasible; therefore, screening will need to be restricted to
      people at high risk of this disease. The proportion of patients with pancreatic
      cancer who also have hyperglycaemia or diabetes has previously been under
      appreciated. New data show that up to 80% of patients are either hyperglycaemic
      or diabetic, both of which can be detected in the presymptomatic phase. Diabetes
      has been shown to improve after pancreatic-cancer resection, suggesting that
      diabetes is caused by the cancer. Conversely, older patients with new-onset
      diabetes have about an eight-times higher risk of having pancreatic cancer than
      the general population. Recognition of new-onset diabetes as an early
      manifestation of pancreatic cancer could lead to the diagnosis of asymptomatic,
      early-stage pancreatic cancer. However, primary type-2 diabetes is common in the
      general population and pancreatic cancer is relatively uncommon, and the two
      forms of diabetes are clinically indistinguishable. The success of a strategy
      using new-onset hyperglycaemia and diabetes as a screening tool to identify
      people with a high likelihood of having asymptomatic pancreatic cancer will
      depend largely on our ability to differentiate pancreatic-cancer-associated
      diabetes from the more common type-2 diabetes by use of a (serological)
      biomarker.

PMID- 19111252
TI  - Study modules for the paraoptometric.

PMID- 19111253
TI  - Visually impaired caregivers: perspectives from patient focus groups.
AB  - BACKGROUND: With the aging of the population, more persons who are severely
      visually impaired are now caring for a spouse or significant other. The purpose
      of this qualitative study is to learn more about this previously unreported, yet
      vulnerable, population of visually impaired caregivers. METHODS: Focus groups and
      1-on-1 interviews were conducted with legally blind U.S. English-speaking adults
      who served as informal caregivers of adults. Visually impaired caregivers
      discussed the challenges of caregiving and how their visual impairment affected
      their caregiving responsibilities. Interview transcripts were analyzed using
      grounded theory. Standardized questionnaires captured demographic and social
      characteristics. RESULTS: Fourteen adults participated. Seven major themes
      emerged from the interviews: (1) impact of lack of transportation, (2) concern
      over care recipient's quality of life, (3) utilization of support, (4) all
      encompassing demand, (5) cyclical adaptations, (6) anxieties of the caregivers,
      and (7) positive aspects of caregiving. CONCLUSIONS: Although visually impaired
      caregivers experience challenges similar to other caregivers, they differ in
      their report of added burden because of visual impairment, with extraordinary
      difficulty in transportation issues and the necessity of cyclical adaptations as
      their vision worsens. This is, to our knowledge, the first qualitative study of
      visually impaired caregivers and brings to light the unique problems faced by
      this special cohort of caregivers.

PMID- 19111254
TI  - A presentation of longstanding toxoplasmosis chorioretinitis.
AB  - BACKGROUND: Toxoplasmosis gondii is the most common cause of focal necrotizing
      retinitis in healthy individuals. This case report describes a presentation of
      toxoplasmosis chorioretintis and reviews the current management options. CASE
      REPORT: A 10-year-old Hispanic girl presented with complaints of decreased vision
      in her right eye for 3 weeks. The patient had presumed ocular toxoplasmosis
      chorioretinitis with secondary granulomatous panuveitis. She was treated
      successfully with Bactrim (Roche Laboratories, Nutley, New Jersey) and topical
      steroids and cylcoplegics. CONCLUSION: Ocular toxoplasmosis is a self-limiting
      disease in immunocompetent individuals; however, proper diagnosis and early
      intervention improves visual outcome.

PMID- 19111255
TI  - Comprehensive vision care in urban communities: the pediatric outreach program.
AB  - BACKGROUND: The Illinois College of Optometry's (ICO) Pediatric Outreach Program
      (POP) provides comprehensive vision care for high-risk children from birth to
      approximately 5 years of age in partnership with early intervention programs
      throughout the city of Chicago. Grant funds assisted in the ability to deliver
      vision services and spectacles to uninsured children. This report describes the
      structure and organization of the POP and presents the visual data. METHODS:
      Comprehensive eye examinations were performed on 4,298 children ages birth to
      approximately 5 years at 76 early intervention program sites. All of the children
      evaluated were enrolled from early intervention/Head Start programs. Visual
      acuity determination (by Lea method), assessment of binocular status, stereopsis
      evaluation, cycloplegic retinoscopy, and ocular health evaluations were
      performed. As necessary, eyeglasses were prescribed. Amblyogenic risk factors,
      strabismus, and ocular pathology were identified. RESULTS: Of the 4,298 children
      examined, 49% were boys and 51% were girls. Two percent were younger than 12
      months old, 6% were 1.1 to 2 years old, 12% were 2.1 to 3 years, 30% were 3.1 to
      4 years, 35% were 4.1 to 5 years, 14% were 5.1 to 6 years, and 1% were older than
      6 years. Hyperopia and emmetropia were the most common refractive classifications
      among the children examined. Approximately 6.5% had risk factors for isometropic
      amblyopia, and 2.3% had risk factors for anisometropic amblyopia. Approximately
      1% of the children had strabismus. Less than 1% of the children examined were
      identified with ocular pathology. Spectacles were dispensed to 16.6% of the
      children examined. CONCLUSIONS: The Pediatric Outreach Program provides early
      identification and treatment of abnormal visual conditions, ensuring that
      children have maximal visual acuity and visual function. The educational aspects
      of the program have also contributed to its successes. Education for parents and
      early intervention agency staff promote the importance of comprehensive vision
      examinations for children 5 years of age and younger.

PMID- 19111256
TI  - Congenital rubella syndrome--major review.
AB  - Congenital rubella syndrome is a rare disorder with devastating ocular and
      systemic consequences. Although efforts to eradicate the disease have been in
      place for some time, some areas of the world continue to be affected by this
      disease. The burden of the disease weighs heavily on patients and society;
      therefore, vaccination and other preventative strategies should continue to be
      strongly encouraged.

PMID- 19111257
TI  - Fostering quality spine care for patients.

PMID- 19111258
TI  - Is the self-reported history accurate in patients with persistent axial pain
      after a motor vehicle accident?
AB  - BACKGROUND CONTEXT: A patient's self-reported history has, in general, assumed to
      be accurate. Clinical management of individuals with persistent axial pain after
      a motor vehicle accident (MVA) and measures to prevent future MVA, spinal cord
      injury, and traffic deaths often depend on a presumed accurate report of
      preexisting axial pain, drug, alcohol, and psychological problems to initiate
      intervention. In addition, research efforts to determine the effects of MVA on
      subsequent health are often predicated on a presumed accurate history from the
      patient of past medical and psychosocial problems. Despite so many clinical,
      public health, and research efforts being dependent on an accurate assessment of
      pre-injury health, the validity of the self-reported history after MVA has not
      been systematically investigated. PURPOSE: To determine the validity of self
      reported history in subjects with axial neck or back pain attributed to a recent
      MVA. STUDY DESIGN: A prospective, multiclinic validation study examining the
      critical elements of a patient's self-reported history after an MVA judged
      against an audit of his or her medical records. PATIENT SAMPLE: A cohort of
      consecutive patients with persistent axial pain after an MVA was prospectively
      identified from five spine-specialist's outpatient clinics. Of 702 patients, 335
      subjects were randomly selected for auditing of their medical records. OUTCOME
      MEASURES: Self-reported demographic and clinical features were recorded by
      standardized questionnaires and clinical interviews. Audits compared these
      responses to an extensive medical record search. METHODS: The self-reported
      prevalence of preexisting axial pain, at-risk comorbidities (psychological
      distress, alcohol, and drug abuse), and control conditions (hypertension and
      diabetes) was recorded. The medical records of a random sample of 50% of the
      enrolled cohort underwent auditing of their medical records in a wide search of
      network paper and electronic and archived records, and compared with the self
      reported history of pre-accident health. RESULTS: Overall, approximately 50% of
      the subjects were found to have previous axial pain problems at audit when none
      was reported to the spine-specialist after an MVA. Similarly, approximately 75%
      of the subjects were found to have one or more preexisting comorbid conditions at
      audit that were not reported during the evaluation after the MVA (alcohol abuse,
      illicit drug use, and psychological diagnosis). For those who perceived that the
      accident was the fault of another, as opposed to their own or no one's fault, the
      documented previous back and neck pain troubles in the medical records was more
      than twice the self-reported rate of these problems (p<.01). The rate of
      previously documented psychological problems was more than seven times that of
      the self-reported rate (p = 0.001). In those subjects who perceived that the
      accident was their own or no one's fault, a lesser degree of under-reporting of
      axial pain and comorbid conditions was found. CONCLUSION: The validity of the
      patient's self-reported history when presenting with persistent axial pain after
      an MVA appears poor in this large multiclinic random sample.The self-reported
      rates of alcohol abuse, illicit drug use, and psychological diagnosis, as well as
      prior axial pain were significantly lower than that seen in the medical records,
      especially in thosewho perceive that the MVA was another's fault. The failure to
      recognize this under-reporting may seriously compromise clinical care, public
      health efforts at injury prevention, and research protocols dependent on accurate
      pre-accident morbidity assessments.

PMID- 19111259
TI  - The Twin Spine Study: contributions to a changing view of disc degeneration.
AB  - BACKGROUND CONTEXT: Disc degeneration was commonly viewed over much of the last
      century as a result of aging and "wear and tear" from mechanical insults and
      injuries. Thus, prevention strategies and research in lumbar degenerative changes
      and associated clinical conditions focused largely on mechanical factors as
      primary causes using an "injury model." The Twin Spine Study, a research program
      on the etiology and pathogenesis of disc degeneration, has contributed to a
      substantial revision of this view of determinants of lumbar disc degeneration.
      PURPOSE: To provide a review of the methods and findings of the Twin Spine Study
      project. STUDY DESIGN/SETTING: Narrative review of the Twin Spine Study. METHODS:
      The Twin Spine Study, which started in 1991, is a multidisciplinary,
      multinational research project with collaborators primarily in Canada, Finland,
      and the United States. The most significant investigations related to
      determinants of disc degeneration included occupational exposures, driving and
      whole-body vibration exposure, smoking exposure, anthropomorphic factors,
      heritability, and the identification of genotypes associated with disc
      degeneration. RESULTS: Among the most significant findings were a substantial
      influence of heredity on lumbar disc degeneration and the identification of the
      first gene forms associated with disc degeneration. Conversely, despite
      extraordinary discordance between twin siblings in occupational and leisure-time
      physical loading conditions throughout adulthood, surprisingly little effect on
      disc degeneration was observed. Studies on the effects of smoking on twins with
      large discordance in smoking exposure demonstrated an increase in disc
      degeneration associated with smoking, but this effect was small. No evidence was
      found to suggest that exposure to whole-body vibration through motorized vehicles
      leads to accelerated disc degeneration in these well-controlled studies. More
      recent results indicate that the effect of anthropometric factors, such as body
      weight and muscle strength on disc degeneration, although modest, appear in this
      work to be greater than those of occupational physical demands. In fact, some
      indications were found that routine loading may actually have some benefits to
      the disc. CONCLUSIONS: The once commonly held view that disc degeneration is
      primarily a result of aging and "wear and tear" from mechanical insults and
      injuries was not supported by this series of studies. Instead, disc degeneration
      appears to be determined in great part by genetic influences. Although
      environmental factors also play a role, it is not primarily through routine
      physical loading exposures (eg, heavy vs. light physical demands) as once
      suspected.

PMID- 19111260
TI  - Health reform and imaging.

PMID- 19111261
TI  - CME for reading JACR.

PMID- 19111262
TI  - Radiology group (un)governance.

PMID- 19111263
TI  - Do you really want that package?

PMID- 19111264
TI  - Faculty development: meeting the challenge.

PMID- 19111265
TI  - Making the grade: levels of leadership, part 1.

PMID- 19111266
TI  - Incidental extracolonic findings on CT colonography: the impending deluge and its
      implications.
AB  - The probable future widespread adoption of computed tomographic colonography
      (CTC) will lead to the detection of numerous incidental extracolonic findings
      (ECFs). Defining, characterizing, and making diagnostic and management
      recommendations for such ECFs are likely to be inconsistent and, averaged over
      the patient population, may be more costly than CTC itself. Several reports that
      suggested a modest cost for evaluating ECFs did not include all of the downstream
      costs of diagnosis and treatment, while studies that more closely tracked costs
      arrived at figures up to 5 times as high. The ECF aspect of CTC is analogous to
      total-body screening, which has been widely criticized, and the cost
      effectiveness of evaluating and managing ECFs is unproven and controversial,
      which also has implications for managing incidental findings from other
      applications for abdominal and pelvic computed tomography. The author reviews
      studies that have assessed the frequency, costs, and effects of ECFs.
      Establishing national or local criteria for detecting ECFs and providing
      recommendations for referring clinicians may be an important step toward
      achieving the most effective patient care for ECFs, which are the inevitable
      consequence of performing CTC.

PMID- 19111267
TI  - RADPEER scoring white paper.
AB  - The ACR's RADPEER program began in 2002; the electronic version, e-RADPEER, was
      offered in 2005. To date, more than 10,000 radiologists and more than 800 groups
      are participating in the program. Since the inception of RADPEER, there have been
      continuing discussions regarding a number of issues, including the scoring
      system, the subspecialty-specific subcategorization of data collected for each
      imaging modality, and the validation of interfacility scoring consistency. This
      white paper reviews the task force discussions, the literature review, and the
      new recommended scoring process and lexicon for RADPEER.

PMID- 19111268
TI  - The power of pink: cause-related marketing and the impact on breast cancer.
AB  - The pink ribbon is one of the most widely recognized symbols in the United
      States. It can symbolize strength, hope, responsibility, empathy, and permission
      to discuss breast cancer, though not all associations are uniformly positive.
      Cause-related marketing is an agreement between nonprofit and for-profit
      organizations to promote a product that provides benefit for the cause through
      increasing awareness and financial contributions from sales. For-profit
      organizations benefit through the association of the positive ideology of the
      pink ribbon. The relationship between the organizations should be mutually
      beneficial; the percentage of funds donated should be reasonable, and the
      organizations that benefit should be respected institutions. Many breast cancer
      organizations have obtained significant benefit from corporate partnerships in
      cause-related marketing. Certainly, breast cancer awareness is much stronger now
      than 15 years ago. However, not all products are appropriate for promotion,
      particularly products that may increase the risk for breast cancer, such as
      alcohol. No corporation is licensed to have exclusive use of the pink ribbon
      symbol, leaving it open to potential abuse. Backlash by consumers has raised
      awareness of the misuse of the pink ribbon and cause-related marketing. As
      marketing becomes more global, the impact of the pink ribbon in the third world
      may spur open dialogue and reduce the taboo associated with breast cancer
      observed in some cultures.

PMID- 19111269
TI  - Randomized prospective trials of innovative radiotherapy technology are
      necessary.
AB  - The most important clinical problem facing radiation oncology is whether
      randomized prospective trials are necessary to assess innovative technologies.
      Some radiation oncologists feel strongly that randomized trials are unnecessary,
      because highly conformal beams are self-evidently worthy, and the only
      interesting question is the magnitude of the gain, not whether a gain is
      achievable. Supporters of randomized trials invoke a long list of historical
      examples wherein such trials demonstrated the uselessness of technologies that
      were thought to be "self-evidently" better. Physicians with financial or academic
      career interest in the promotion of innovative technologies are not objective
      parties in this debate. There are also considerable opportunity costs of
      investments in expensive innovative technologies. It is possible to identify
      innovations that should be required to meet the standard of proof of a benefit in
      a randomized prospective clinical trial before being introduced into widespread
      clinical practice.

PMID- 19111270
TI  - Patient-physician communication: informed consent for imaging-guided spinal
      injections.
AB  - PURPOSE: Historically, informed-consent forms have been developed for the purpose
      of educating patients. However, informed-consent forms can be very difficult to
      understand. The hypothesis of this study was that a method using diagrams would
      improve patient-physician communication without increasing the time required to
      obtain informed consent over the teach-the-teacher method, as well as over
      current standard informed-consent protocol. METHODS: Ninety-nine of 109 patients
      undergoing spinal injections agreed to participate and completed this
      prospective, randomized, controlled study. The patients were randomly assigned to
      the control group (informed consent obtained in the customary manner at the
      investigators' institution, with 12 key points of consent and home care discussed
      conversationally), the teach-the-teacher group (patients had to repeat the 12 key
      points to the physicians before informed consent was complete), and the diagram
      group (patients viewed a set of diagrams illustrating the 12 key points before
      signing the informed-consent form). After the procedure, the patients completed a
      survey to test knowledge recall, anxiety, and pain during the procedure. RESULTS:
      Statistically significant results included a lower survey score for the control
      group, longer time required for the teach-the-teacher group than the control
      group, and a negative correlation between age and survey score in the teach-the
      teacher group. CONCLUSIONS: The diagram method required less time than the teach
      the-teacher method, had no negative correlation in survey score results with age,
      and had improved patient-physician communication over the control group.

PMID- 19111271
TI  - Developing a radiation error scoring system to monitor quality control events in
      a radiation oncology department.
AB  - PURPOSE: The aims of this study were to evaluate the factors contributing to
      errors in the treatment of cancer patients undergoing radiation therapy and to
      develop a grading system that allows for the comparison of errors. METHODS:
      Deviations in the prescribed treatment of patients undergoing radiation therapy
      were collected during 2003 in the Department of Radiation Oncology at Fox Chase
      Cancer Center. The deviations were classified according to responsibility as
      follows: therapist, physician, dosimetrist, physicist, machine, or all. The
      deviations in treatment were graded on an increasing scale ranging from 1 to 4,
      according to severity. Error analysis was made corresponding to treatment
      machine, therapist, dosimetrist, type of treatment, palliative or definitive
      treatment, type of cancer, time of occurrence, and machine census at the time of
      occurrence. RESULTS: A total of 33,757 patient treatments were delivered on 4
      linear accelerators with 3,646 dose calculations performed by the physics staff
      during 2003. All treatments, both intensity-modulated radiation therapy and
      conventional therapy, were considered in this analysis. A total of 25 quality
      control (QC) events occurred during the study period. The crude error rate for
      therapists was 0.041%, and the crude error rate for dosimetrists and physicists
      was 0.22%. There were 17 level I errors (2 machine, 1 block mismounting, 4
      dosimetrist, 1 all, and 9 therapist), 5 level II errors (3 dosimetrist, 1
      therapist and dosimetrist, and 1 therapist), and 3 level III errors (3
      therapist). Fifteen of the 25 QC events and 8 of 13 therapist events occurred
      after 12 pm. A correlation did not exist between the time of occurrence and
      machine census at the time of the QC events. However, more level I events
      occurred after 12 pm than before 12 pm. CONCLUSIONS: A review of QC events
      occurring during the course of radiation treatments allowed a change in the
      process of care to prevent the occurrence of some QC events. The QC event rate
      experienced by the department compares favorably with published results from
      similar academic centers. The periodic review of QC events allows for the
      opportunity to identify processes that can be adapted to reduce the occurrence of
      QC events in the future.

PMID- 19111272
TI  - Observational research in trauma radiology: should patients be informed?
AB  - The need for prospective studies in trauma radiology emerges as knowledge on the
      appropriate use of imaging becomes increasingly important in this field.
      Prospective observational studies enroll patients after research questions are
      articulated but only observe medical practice and should not compromise or change
      patient treatment. However, controversy exists regarding the requirement of
      informed consent from trauma patients in this type of study. This is reflected
      not only in differences in reporting informed consent in recent scientific
      publications on trauma radiology but also by the fact that policies regarding
      this topic vary in different parts of the world. The authors consider whether
      requesting informed consent is appropriate in prospective observational studies
      in trauma radiology from practical and different ethical perspectives.

PMID- 19111273
TI  - Significantly expanded anti-markup rule goes into effect January 1, 2009.

PMID- 19111274
TI  - Reviewing images from portable media: an ongoing challenge.

PMID- 19111275
TI  - Dual-source CT for cardiac imaging.

PMID- 19111277
TI  - Measures of acidosis with repetitive umbilical cord occlusions leading to fetal
      asphyxia in the near-term ovine fetus.
AB  - OBJECTIVE: Increasing frequency of severe variable decelerations is associated
      with acidemia. However, there is little understanding of its development or
      normalization rate. STUDY DESIGN: To quantify the time course of acidemia, 10
      near-term fetal sheep underwent a series of mild (1 minute every 5 minutes),
      moderate (1 minute every 3 minutes), and severe (1 minute every 2 minutes)
      umbilical cord occlusions (UCO), lasting 1 hour each or until fetal arterial pH
      decreased to less than 7.00. RESULTS: Each minute of UCO resulted in base deficit
      (BD) and lactate increases at rates of 0.56 and 0.35 mmol/L per minute,
      respectively. During a 2 h recovery, BD and lactate normalized at rates of 0.09
      and 0.04 mmol/L per minute. BD correlated highly with lactate (r = 0.95; P <
      .001). CONCLUSION: Our findings in the near-term ovine fetus suggest that the
      knowledge of fetal BD deterioration and recovery rates can aid assessing fetal
      acidemia during labor.

PMID- 19111278
TI  - Amphetamine-induced place preference in humans.
AB  - BACKGROUND: The conditioned place preference procedure is a widely used animal
      model of rewarding drug effects that, to date, has not been tested in humans. In
      this study, we sought to demonstrate that humans, like nonhumans, would exhibit a
      preference for a place previously associated with amphetamine. Further, we
      investigated the relationship between conditioned place preference and the mood
      altering effects of the drug. METHODS: Thirty-one healthy individuals
      participated in a five-session procedure during which they experienced the
      effects of d-amphetamine (20 mg) or placebo on two occasions in two distinctive
      environments (sessions 1-4). One group of subjects (paired group, n = 19)
      received amphetamine consistently in one room and placebo in another room,
      whereas a second group (unpaired group, n = 12) received amphetamine and placebo
      without regard to room. During the sessions, participants completed
      questionnaires to rate their mood. On the fifth session, they rated their
      preference for the two rooms. RESULTS: Individuals in the paired group rated
      their liking of the amphetamine-paired room significantly higher than the placebo
      associated room, whereas there was no difference between ratings of the two rooms
      for individuals in the unpaired group. In the paired group, drug-liking ratings
      during the conditioning sessions positively predicted preference for the drug
      associated room, whereas reports of amphetamine-induced anxiety and dysphoria
      negatively predicted room-liking scores. CONCLUSIONS: This study demonstrates
      that humans, like nonhumans, prefer a place associated with amphetamine
      administration. These findings support the idea that subjective responses to a
      drug contribute to its ability to establish place conditioning.

PMID- 19111279
TI  - Interleukin-1 receptor antagonist and incident depressive symptoms over 6 years
      in older persons: the InCHIANTI study.
AB  - BACKGROUND: We test the hypothesis that in older persons higher plasma levels of
      inflammatory markers predict the development of depressive symptoms during a 6
      year follow-up. METHOD: This study is part of the InCHIANTI (Invecchiare in
      Chianti, aging in the Chianti area) study, a prospective population-based study
      of older persons. The sample consisted of 991 participants, ages 65 years and
      older. Serum levels of C-reactive protein, interleukin (IL)-1beta, IL-1 receptor
      antagonist (ra), tumor necrosis factor-alpha, IL-6, IL-6 receptor, and IL-18 were
      measured. Depressive symptoms were assessed at baseline and at the 3- and 6-year
      follow-ups with the Center for Epidemiological Studies-Depression Scale (CES-D).
      Depressed mood was defined as CES-D > 20. Potential confounders were baseline
      variables related to sociodemographic, somatic health, and functional status.
      RESULTS: At baseline, IL-1ra levels were significantly higher (p = .004) in
      depressed compared with nondepressed participants. After adjustment for
      confounders, among subjects free of depression at baseline, those in the third
      and fourth IL-1ra quartiles compared with those in the lowest quartile had,
      respectively, a 2.32-fold (95% confidence interval: 1.21-4.42, p = .01) and 2.78
      fold (95% confidence interval: 1.47-5.26, p = .002) higher risk of developing
      depressed mood during a 6-year follow-up. CONCLUSIONS: In old age, persons with
      high plasma levels of IL1-ra had a higher risk of developing depressive symptoms
      over time. These findings suggest a potential causal role for inflammation in the
      development of depressive symptoms in older persons.

PMID- 19111280
TI  - Is persistent ketamine use a valid model of the cognitive and oculomotor deficits
      in schizophrenia?
AB  - BACKGROUND: Acute ketamine has been shown to model features of schizophrenia such
      as psychotic symptoms, cognitive deficits and smooth pursuit eye movement
      dysfunction. There have been suggestions that chronic ketamine may also produce
      an analogue of the disorder. In this study, we investigated the effect of
      persistent recreational ketamine use on tests of episodic and working memory and
      on oculomotor tasks of smooth pursuit and pro- and antisaccades. METHODS: Twenty
      ketamine users were compared with 1) 20 first-episode schizophrenia patients, 2)
      17 polydrug control subjects who did not use ketamine but were matched to the
      ketamine users for other drug use, and 3) 20 non-drug-using control subjects. All
      groups were matched for estimated premorbid IQ. RESULTS: Ketamine users made more
      antisaccade errors than both control groups but did not differ from patients.
      Ketamine users performed better than schizophrenia patients on smooth pursuit,
      antisaccade metrics, and both memory tasks but did not differ from control
      groups. CONCLUSIONS: Problems inhibiting reflexive eye movements may be a
      consequence of repeated ketamine self-administration. The absence of any other
      oculomotor or cognitive deficit present in schizophrenia suggests that chronic
      self-administration of ketamine may not be a good model of these aspects of the
      disorder.

PMID- 19111281
TI  - Brain areas coactivating with motor cortex during chronic motor tics and
      intentional movements.
AB  - BACKGROUND: Chronic tic disorders are characterized by motor tics that are often
      preceded by premonitory urges to tic. Functional neuroimaging studies have
      documented brain activity patterns prior to and during tics, but these studies
      have not examined whether the activation patterns differ from those seen in
      normal control subjects performing similar acts. METHODS: A novel method was used
      to compare brain patterns during tics and intentional movements. First, the part
      of motor cortex specific to each patient's tic movement was identified. The brain
      areas activating prior to, during, and after that part of motor cortex during
      tics were then identified by temporally cross-correlating the time course of the
      localized motor region with activity in other brain areas. Given that motor
      cortex was active during tic execution, this yielded information regarding the
      brain areas active prior to, during, and after the movements. The spatiotemporal
      pattern of coactivation with motor cortex during tics was contrasted with that
      seen in healthy control subjects during intentional tic-like movements. RESULTS:
      Data from 16 adult subjects with tic disorders and 16 matched control subjects,
      who performed intentional movements similar to the patients' tics, revealed
      nearly identical patterns of cross-correlation to motor cortex throughout the
      brain in the two groups. However, the supplementary motor area showed a
      significantly broader profile of cross-correlation to motor cortex during tics
      than during intentional movements. CONCLUSIONS: These findings highlight the
      importance of the supplementary motor area in tic generation and may point toward
      novel intervention strategies for individuals suffering with severe tics.

PMID- 19111282
TI  - Ion-trap mass spectrometry unveils the presence of isomeric oligosaccharides in
      an analyte: stage-discriminated correlation of energy-resolved mass spectrometry.
AB  - Mass spectrometry, especially tandem mass spectrometry, has been widely used in
      the field of analytical sciences for handling biological and chemical samples.
      The technique resolves molecular and fragment ions based on the mass to charge
      ratio. Energy-resolved mass spectrometry (ERMS) further provides an activation
      energy-related factor in the dissociation reaction. Therefore, it is a very
      powerful technique that can discriminate isomeric compounds. Despite the power of
      ERMS, useful information cannot be obtained when an analyte contains structural
      isomers. Carbohydrates carry multiple chiral centers, thus oligomers of
      monosaccharides can form a vast number of structural isomers. We decided to use
      such species in our endeavors to establish a method of identifying the 'purity'
      of an analyte solely based on mass spectrometry. In the present paper, we
      describe a stage-discriminated spectral correlation of ERMS, which not only
      enables identification of the presence of contaminants in an analyte, but also
      provides information regarding the 'purity' of fragment ions.

PMID- 19111283
TI  - The structure of high-methoxyl sugar acid gels of citrus pectin as determined by
      AFM.
AB  - Images of native high-methoxyl sugar acid gels (HMSAGs) were obtained by atomic
      force microscopy (AFM) in the Tapping Mode. Electronic thinning of the pectin
      strands to one-pixel wide allowed the pectin network to be viewed in the absence
      of variable strand widths related to preferentially solvated sugar. Thinned
      images revealed that HMSAGs of pectin comprise a partially cross-linked network,
      in that many of the cross-linking moieties are attached at only one end. Based on
      their structural similarities, aggregated pectin in water appears to be a fluid
      precursor of a HMSAG of pectin. Furthermore, examination of AFM images revealed
      that gels with 'uniform' distribution of strands and pores between strands had
      higher gel strengths than gels in which strands were non-uniformly distributed
      and were separated by large and small spaces.

PMID- 19111284
TI  - Microwave technique for efficient deacetylation of chitin nanowhiskers to a
      chitosan nanoscaffold.
AB  - A chitosan nanoscaffold in the form of a colloidal solution was obtained from the
      deacetylation of chitin whiskers under alkaline conditions by using a microwave
      technique in only 1/7 of the treatment time of the conventional method. Fourier
      transform infrared spectroscopy (FTIR) and nuclear magnetic resonance ((1)H NMR)
      techniques confirm the degree of deacetylation to be above 90% within 3 h. The
      wide-angle X-ray diffraction (WAXD) pattern clearly shows that the highly
      crystalline chitin whiskers are changed to amorphous chitosan. SEM micrographs
      show the aggregation of branched nanofibers, whereas the TEM micrographs reveal
      the scaffold morphology.

PMID- 19111286
TI  - Great apes' capacities to recognize relational similarity.
AB  - Recognizing relational similarity relies on the ability to understand that
      defining object properties might not lie in the objects individually, but in the
      relations of the properties of various object to each other. This aptitude is
      highly relevant for many important human skills such as language, reasoning,
      categorization and understanding analogy and metaphor. In the current study, we
      investigated the ability to recognize relational similarities by testing five
      species of great apes, including human children in a spatial task. We found that
      all species performed better if related elements are connected by logico-causal
      as opposed to non-causal relations. Further, we find that only children above 4
      years of age, bonobos and chimpanzees, unlike younger children, gorillas and
      orangutans display some mastery of reasoning by non-causal relational similarity.
      We conclude that recognizing relational similarity is not in its entirety unique
      to the human species. The lack of a capability for language does not prohibit
      recognition of simple relational similarities. The data are discussed in the
      light of the phylogenetic tree of relatedness of the great apes.

PMID- 19111285
TI  - Reference production in young speakers with and without autism: effects of
      discourse status and processing constraints.
AB  - We examine the referential choices (pronouns/zeros vs. names/descriptions) made
      during a narrative by high-functioning children and adolescents with autism and a
      well-matched typically developing control group. The process of choosing
      appropriate referring expressions has been proposed to depend on two areas of
      cognitive functioning: (a) judging the attention and knowledge of one's
      interlocutor, and (b) the use of memory and attention mechanisms to represent the
      discourse situation. We predicted possible group differences, since autism is
      often associated with deficits in (a) mentalizing and (b) memory and attention,
      as well as a more general tendency to have difficulty with the pragmatic aspects
      of language use. Results revealed that some of the participants with autism were
      significantly less likely to produce pronouns or zeros in some discourse
      contexts. However, the difference was only one of degree. Overall, all
      participants in our analysis exhibited fine-grained sensitivity to the discourse
      context. Furthermore, referential choices for all participants were modulated by
      factors related to the cognitive effort of language production.

PMID- 19111287
TI  - Categorical perception of affective and linguistic facial expressions.
AB  - Two experiments investigated categorical perception (CP) effects for affective
      facial expressions and linguistic facial expressions from American Sign Language
      (ASL) for Deaf native signers and hearing non-signers. Facial expressions were
      presented in isolation (Experiment 1) or in an ASL verb context (Experiment 2).
      Participants performed ABX discrimination and identification tasks on morphed
      affective and linguistic facial expression continua. The continua were created by
      morphing end-point photo exemplars into 11 images, changing linearly from one
      expression to another in equal steps. For both affective and linguistic
      expressions, hearing non-signers exhibited better discrimination across category
      boundaries than within categories for both experiments, thus replicating previous
      results with affective expressions and demonstrating CP effects for non-canonical
      facial expressions. Deaf signers, however, showed significant CP effects only for
      linguistic facial expressions. Subsequent analyses indicated that order of
      presentation influenced signers' response time performance for affective facial
      expressions: viewing linguistic facial expressions first slowed response time for
      affective facial expressions. We conclude that CP effects for affective facial
      expressions can be influenced by language experience.

PMID- 19111288
TI  - Collective representations elicit widespread individual false memories.

PMID- 19111289
TI  - The temporal characteristics of functional activation in Broca's area during
      overt picture naming.
AB  - The opercular and triangular sections of the inferior frontal gyrus, also known
      as Broca's area, have been shown to be involved in various language tasks. In the
      current study we investigated both the functional role, as well as the precise
      temporal involvement of Broca's area during picture naming. We applied online
      event-related transcranial magnetic stimulation (TMS) to Broca's area at five
      different time points after picture presentation, aiming to cover the complete
      language production process. Applying real TMS at 300 msec after picture
      presentation led to an increase in picture naming latency, whereas sham
      stimulation and real stimulation at earlier and later time windows did not result
      in any changes in reaction time (RT). Our methodological approach enabled us to
      get insight into the temporal characteristics of the involvement of this brain
      area during picture naming. Making use of this information and directly relating
      it to psycholinguistic models, we conclude that Broca's area may be involved in
      the process of syllabification during overt speech production.

PMID- 19111290
TI  - Syntax without language: neurobiological evidence for cross-domain syntactic
      computations.
AB  - Not all conceivable grammars are realized within human languages. Rules based on
      rigid distances, in which a certain word must occur at a fixed distance from
      another word, are never found in grammars of human languages. Distances between
      words are specified in terms of relative, non-rigid positions. The left inferior
      frontal gyrus (IFG) (Broca's area) has been found to be involved in the
      computation of non-rigid but not of rigid syntax in the language domain. A
      fundamental question is therefore whether the neural activity underlying this non
      rigid architecture is language-specific, given that analogous structural
      properties can be found in other cognitive domains. Using event-related
      functional magnetic resonance imaging (fMRI) in sixteen healthy native speakers
      of Italian, we measured brain activity for the acquisition of rigid and non-rigid
      syntax in the visuo-spatial domain. The data of the present experiment were
      formally compared with those of a previous experiment, in which there was a
      symmetrical distinction between rigid and non-rigid syntax in the language
      domain. Both in the visuo-spatial and in the language domain, the acquisition of
      non-rigid syntax, but not the acquisition of rigid syntax, activated Brodmann
      Area 44 of the left IFG. This domain-independent effect was specifically
      modulated by performance improvement. Thus, in the human brain, one single
      "grammar without words" serves different higher cognitive functions.

PMID- 19111291
TI  - The neural basis for simulated drawing and the semantic implications.
AB  - This functional magnetic resonance imaging (fMRI) study of the mental simulation
      of drawing (1) investigated the neural substrates of drawing and (2) delineated
      the semantic aspects of drawing. The goal was to advance our understanding of how
      drawing a familiar object is linked to lexical semantics and therefore a viable
      method to use to rehabilitate aphasia. We hypothesized that the semantic aspects
      of drawing familiar objects compared to drawing non-objects would yield greater
      activation in the inferior temporal cortex and the inferior frontal cortex of the
      left hemisphere. To test this hypothesis, eight right-handed subjects performed
      an fMRI experiment that directly contrasted drawing familiar objects to non
      objects using mental imagery. Simulated drawing recruited a large, distributed
      network of frontal, parietal, and temporal structures. In the contrast comparing
      drawing familiar objects to non-objects there was stronger activation in the left
      hemisphere within the inferior temporal, anterior inferior frontal, inferior
      parietal and superior frontal cortices. The activation within the inferior
      temporal cortex was associated with visual semantic processing and semantic
      mediated naming. We suggest that the anterior inferior frontal activation is
      linked to the inferior temporal cortex and is involved in the selection of
      specific semantic features of the object as well as retrieval of information
      regarding the perceptual aspects of the object.

PMID- 19111292
TI  - Leftward motion restores number space in neglect.
AB  - In the present study, a group of patients with left-sided neglect performed a
      number comparison task that co-occurred either with coherent motion in different
      directions or with random motion. Their performance was compared to that of a
      healthy control group and to a group of patients with right hemisphere damage
      (RHD) but no signs of neglect. The presence of leftward motion alleviated the
      difficulties that neglect patients typically show for a number smaller than the
      reference number 5 (i.e., number 4). Moreover, the standard distance effect was
      only present when the task co-occurred with leftward motion. These effects were
      not present in a group of participants with RHD without neglect or in a control
      group. The present data extend the effects of optokinetic stimulation (OKS) to
      representational neglect, suggesting that an external redirection of attention by
      the perception of motion may restore the altered access to the representation of
      the mental number line in neglect.

PMID- 19111293
TI  - Absence of chlamydial deoxyribonucleic acid from testicular and epididymal
      samples from men with obstructive azoospermia.
AB  - OBJECTIVE: To identify Chlamydia trachomatis DNA by polymerase chain reaction in
      the upper genital tract of men with obstructive azoospermia compared with men
      seeking vasectomy reversal. DESIGN: Case-control study. SETTING: Tertiary
      referral center, Aberdeen Royal Infirmary, Aberdeen, United Kingdom. PATIENT(S):
      Cases were men with idiopathic obstructive azoospermia, and controls were men
      with azoospermia secondary to vasectomy. INTERVENTION(S): Chlamydia trachomatis
      specific DNA test by polymerase chain reaction on testicular and epididymal
      biopsy samples, as well as epididymal aspirate. MAIN OUTCOME MEASURE(S): Presence
      of Chlamydia trachomatis DNA. RESULT(S): We did not detect the presence of
      Chlamydia trachomatis-specific DNA by polymerase chain reaction in the epididymis
      or testis of 36 asymptomatic men with obstructive azoospermia (14 cases, 22
      controls). CONCLUSION(S): Our hypothesis that unrecognized, asymptomatic
      chlamydial infection will lead to complete bilateral obstruction of the male
      genital tract remains unproven.

PMID- 19111294
TI  - Rod outer segment membrane guanylate cyclase type 1 (ROS-GC1) calcium-modulated
      transduction system in the sperm.
AB  - OBJECTIVE: Evaluation of the presence of a Ca(2+)-regulated membrane guanylate
      cyclase signal transudation system in the spermatozoa. DESIGN: Experimental
      study. SETTING: Research university laboratory. PATIENT(S): Human sperm obtained
      from healthy donors who met the criteria of the World Health Organization for
      normozoospermia and bovine semen collected from bulls of proven fertility.
      INTERVENTION(S): Radioimmunoassay and immunohistochemistry of human and bovine
      spermatozoa. MAIN OUTCOME MEASURE(S): The membrane guanylate cyclase activity and
      the presence of membrane guanylate cyclase transduction machinery components in
      the spermatozoa. RESULT(S): The identity of a Ca(2+)-modulated membrane guanylate
      cyclase transduction machinery in human and bovine spermatozoa has been
      documented. The machinery is both inhibited and stimulated within nanomolar to
      semimicromolar range of free Ca(2+). The transduction component of this machinery
      is the rod outer segment membrane guanylate cyclase type 1 (ROS-GC1). The enzyme
      coexists with three Ca(2+)-dependent modulators: guanylate cyclase activating
      protein type 1 (GCAP1), S100B and neurocalcin delta. ROS-GC1 and its modulators
      are present in the heads and tails of both species' spermatozoa. CONCLUSION(S):
      The coexpression of ROS-GC1 and its activators in spermatozoa suggests that the
      Ca(2+)-modulated ROS-GC1 transduction system may be a part of the fertilization
      machinery.

PMID- 19111295
TI  - Insulinoma and pregnancy.

PMID- 19111296
TI  - Granulosa-lutein cell growth differentiation factor-9 (GDF-9) messenger RNA and
      protein expression in in vitro fertilization (IVF) cycles: relation to
      characteristics of ovulation induction and IVF.
AB  - Granulosa-lutein cell growth differentiation factor-9 (GDF-9), a member of the
      transforming growth factor beta (TGF-beta) superfamily, is an oocyte-derived
      factor expressed throughout the development of the maturing follicle and is
      essential in early follicular development and fertility. Both GDF-9 messenger RNA
      and protein are detected in granulosa-lutein cells. A statistically significant
      correlation between GDF-9 expression and the number of dominant follicles on the
      day human chorionic gonadotropin is administered also is demonstrated. Human
      granulosa-lutein cell GDF-9 expression may play a role in folliculogenesis
      dependent on follicle-stimulating hormone in the in vitro fertilization cycle.

PMID- 19111297
TI  - Impact of age and gender interaction on circulating endothelial progenitor cells
      in healthy subjects.
AB  - OBJECTIVE: To assess the level of circulating endothelial progenitor cells (CEPC)
      in cycling women compared with men and menopausal women. DESIGN: Controlled
      clinical study. SETTING: Healthy, nonsmoking volunteers. PATIENT(S): Twelve
      women, aged 18-40 years, with regular menstrual cycles, 12 menopausal women, and
      two groups of 12 age-matched men were recruited. Women did not receive any
      hormone therapy. INTERVENTION(S): Collection of 20 mL of peripheral blood. MAIN
      OUTCOME MEASURE(S): The number of CEPC, defined as (Lin-/7AAD-/CD34+/CD133+/KDR+)
      cells per 10(6) mononuclear cells (MNC), was measured by flow cytometry.
      RESULT(S): The number of CEPC was significantly higher in cycling women than in
      age-matched men and menopausal women (26.5 per 10(6) MNC vs. 10.5 per 10(6) MNC
      vs. 10 per 10(6) MNC, respectively). The number of CEPC was similar in menopausal
      women, age-matched, and young men. CONCLUSION(S): The number of CEPC is
      influenced by an age-gender interaction. This phenomenon may explain in part the
      better vascular repair and relative cardiovascular protection in younger women as
      compared with age-matched men.

PMID- 19111298
TI  - Effect of metformin on serum visfatin levels in patients with polycystic ovary
      syndrome.
AB  - OBJECTIVE: To evaluate serum visfatin levels and to determine the effects of
      metformin treatment on visfatin levels in patients with polycystic ovary syndrome
      (PCOS). DESIGN: Cross-sectional study. SETTING: University hospital. PATIENT(S):
      Nineteen patients with PCOS and 21 controls. INTERVENTION(S): Metformin was given
      to patients with PCOS, and serum visfatin levels were measured before and after
      treatment. MAIN OUTCOME MEASURE(S): Glucose, triglycerides, high-density
      lipoprotein cholesterol, low-density lipoprotein cholesterol, DHEAS, total T,
      insulin, homeostatic model assessment for insulin resistance (HOMA-IR), and
      visfatin levels were measured. RESULT(S): Serum visfatin levels were
      significantly higher in women with PCOS than in controls. Visfatin could
      differentiate between women with and without increased diabetogenic risk at a cut
      off value of 19.24 ng/mL, with a sensitivity of 93.3% and a specificity of 84%.
      In bivariate analysis of subjects, T, insulin, and waist circumference were
      significantly and positively correlated with visfatin. Treatment resulted in a
      significant decrease in body mass index and a decrease in visfatin concentration.
      After therapy, statistically significant decreases in HOMA-IR, fasting insulin,
      free T, and DHEAS concentrations were observed for the PCOS group. CONCLUSION(S):
      Circulating visfatin levels were higher in patients with PCOS than healthy
      controls, and metformin treatment significantly reduced circulating visfatin
      concentrations after 3 months of therapy.

PMID- 19111299
TI  - Post-biopsy bovine embryo viability and whole genome amplification in
      preimplantation genetic diagnosis.
AB  - OBJECTIVE: To evaluate the effect of the biopsy of 8-cell to 16-cell bovine
      embryos on their subsequent development and the effect of whole genome
      amplification (WGA) on removed blastomeres. DESIGN: Randomized study. SETTING:
      Molecular genetics and animal reproduction laboratories. PATIENT(S): Cow ovaries
      obtained from slaughterhouses. INTERVENTION(S): The ovaries were punctured, and
      the oocytes were matured and fertilized in vitro. On the fourth day after
      fertilization, 8-cell to 16-cell bovine embryos were biopsied, one quarter of
      each embryo being removed. The blastomeres were submitted to WGA followed by
      polymerase chain reaction (PCR). The embryos were returned to culture for
      evaluation of their development. MAIN OUTCOME MEASURE(S): Subsequent rate of
      blastocyst development, embryo cell number, WGA efficiency, and sex
      determination. RESULT(S): A total of 92 embryos were submitted to biopsy. The
      blastocyst production was 53.3%, with 44.9% of hatching rate. These results were
      similar to those of the control group (66.0% and 42.6%) of 103 embryos. Overall,
      no impact was detected on embryo quality in blastocyst cell number between the
      two groups. Removed blastomeres were submitted to WGA, resulting in 98.2% of
      efficiency. However, only 59% of the samples were sexed by PCR. CONCLUSION(S):
      Biopsy of 8-cell to 16-cell bovine embryos did not affect their subsequent
      development. WGA was successful in removed blastomeres.

PMID- 19111300
TI  - Local complications following pancreatic trauma.
AB  - BACKGROUND: Major trauma to the pancreas is uncommon, but associated with
      significant overall morbidity and mortality. A vast majority of these adverse
      outcomes can be attributed to the presences of associated injuries. Among those
      patients who survive the initial injury, however, the subsequent development of
      pancreas-related complications represents a significant source of adverse
      outcomes. METHODS AND RESULTS: A total of 257 patients admitted from January 1996
      to April 2007 were identified from the trauma registry database at our
      institution. One hundred and eighty-three patients surviving more than 48 h after
      admission were selected for analysis. These patients were grouped according to
      the surgical management utilised to address their pancreatic injuries: either
      resection or operative drainage. After exclusion of patients with associated
      vascular injuries, those undergoing drainage had lower rate of associated hollow
      viscus injuries (51.9% vs. 69.9%; p = 0.016) and lower rates of associated solid
      organ injuries (44.2% vs. 70.9%; p < or = 0.001). Patients undergoing drainage
      were noted to have a higher incidence of pseudocyst formation (19.5% vs. 9.0%;
      OR: 2.47, 95% CI, 0.92-6.67; p = 0.068), but lower hospital lengths of stay
      (18.7+/-18.5 vs. 33.8+/-63.5; p = 0.001). No difference in mortality was noted
      between the two populations (5.7% vs. 3.0%; p = 0.700). After multivariate
      analysis pseudocyst formation was the only complication that proved different
      between the two management groups, with patients undergoing operative drainage
      more commonly developing this adverse sequela (OR: 2.93, 95% CI, 1.02-8.36; p =
      0.041). CONCLUSIONS: In the absence of vascular injury, the choice of surgical
      management did not affect adjusted mortality or the overall occurrence of
      pancreas-related complications. Individuals treated with operative drainage
      alone, however, were significantly more likely to develop a post-operative
      pseudocyst than their resectional counterparts.

PMID- 19111301
TI  - Repeat LEEP conization in patients with cervical intraepithelial neoplasia grade
      3 and positive ectocervical margins.
AB  - OBJECTIVE: To evaluate the effectiveness of repeat loop electrosurgical excision
      procedure (LEEP) conization in patients with cervical intraepithelial neoplasia
      (CIN) grade 3 and positive ectocervical margins. METHOD: A retrospective study of
      56 women who underwent repeat LEEP conization for CIN 3 and positive ectocervical
      margins. RESULTS: Final diagnosis after repeat LEEP conization revealed 6 women
      (10.7%) with microinvasive squamous cell carcinoma (Stage IA1); 1 (1.8%) with CIN
      1; 1 (1.8%) with CIN 2; 21 (37.5%) with CIN 3; and 27 (48.2%) with chronic
      cervicitis. Ectocervical or endocervical margins were negative after repeat LEEP
      conization in the majority of women, except for 2 patients (3.6%) with CIN 3 and
      positive ectocervical margins. Recurrence rate for the median follow-up time of 2
      years was 6.1% (3 patients). CONCLUSION: Repeat LEEP conization can reveal
      undiagnosed microinvasive cervical carcinoma in women with positive ectocervical
      margins.

PMID- 19111302
TI  - Depression among Nigerian women following pregnancy loss.
AB  - OBJECTIVE: To determine the level of depression in Nigerian women following
      spontaneous pregnancy loss and the coping strategies used. METHODS: A
      questionnaire survey of 202 Nigerian women who had involuntary pregnancy loss
      over a 1-year period. The Zung Self-Rating Depression Scale was used to assess
      the women. RESULTS: Two-thirds of the pregnancy losses occurred before 20 weeks
      of gestation and one-third occurred after 20 weeks. The majority of respondents
      (74.3%) had minimal depressive symptoms (scoring 50-59 on the depression scale),
      3% had moderate symptoms (scoring 60-69), and 13.9% had severe symptoms (scoring
      70-80). Risk factors for moderate to severe depression included being married,
      previous pregnancy loss, loss of a male fetus, childlessness, and losses after 20
      weeks (P<0.05). Presence of a woman's husband, children, parents and relatives,
      friends, and religious observance were identified as positive coping strategies.
      CONCLUSION: Most Nigerian women suffer some level of depression following
      pregnancy loss, with no living children and losses after 20 weeks being the most
      significant risk factors.

PMID- 19111303
TI  - Reproductive outcome following resectoscope metroplasty in women having a
      complete uterine septum with double cervix and vagina.
AB  - OBJECTIVE: To evaluate reproductive outcomes in women with complete uterine
      septum with double cervix and vagina following resectoscope metroplasty. METHODS:
      The pregnancy outcomes of 21 women who underwent vaginal and uterine septum
      resection were compared with those of 15 untreated women with similar clinical
      characteristics. The Fisher exact test and the Mann-Whitney test were used for
      statistical analysis. RESULTS: Cycle fecundity was better (33.4%+/-28.5% vs
      12.2%+/-4.7%; P=0.046), the rate of term delivery significantly increased
      (P<0.05), and the rate of spontaneous abortion decreased (P<0.05) in the
      treatment group. CONCLUSION: Resectoscope metroplasty was found to improve the
      pregnancy outcomes of women having primary infertility or a history of pregnancy
      loss associated with a complete uterine septum with double cervix and vagina.

PMID- 19111304
TI  - Inflammatory markers in pre-eclampsia and related conditions.

PMID- 19111305
TI  - The ethics and politics of home care.
AB  - BACKGROUND: In the dominant health-care policy, commonly referred to as New
      Public Management, primary emphasis is placed on the reduction of costs in health
      care. This development threatens to increase inequality in society based on
      levels of health or impairment and on gender. AIM: The aim of this paper is
      therefore to raise awareness among nurses about the impact of New Public
      Management and explore how they might develop services that meet the diverse
      needs and wishes of those being served. THEORETICAL APPROACH AND METHOD: Although
      this policy has been criticised by nurses, it has also been observed that they
      are key players in its realisation. This discussion paper explores the impact of
      different discourses upon the practice of home-nursing care. It was developed
      within the post-structural tradition, where discourses are considered of key
      importance in shaping practice. Discourses represent different viewpoints and
      interests, and determine what can be considered meaningful and possible. The
      empirical studies which form the base for many of the main arguments presented
      were identified through an extensive review of published ethnographic research of
      home care in the years 2000-2008. RESULTS: A review of studies conducted in a
      number of countries both in North America and Europe showed that home-care
      services have in many ways been diminished. Clients and their caregivers
      experience insecurity and wish for more assistance. With New Public Management
      the focus has shifted from an ethical discourse to an economic one, although this
      shift has not been clearly articulated and critiqued. By understanding the impact
      of New Public Management, nurses can better focus their practice to meet the
      diverse needs of patients and their caregivers. CONCLUSION: In order to be able
      to respond to retrenchment in health services, nurses need to understand the
      complex ethical and political issues of New Public Management. A number of
      practices can be developed for working with patients and their families in such a
      way that their needs and wishes are respected.

PMID- 19111306
TI  - Identifying thresholds for relationships between impacts of rationing of nursing
      care and nurse- and patient-reported outcomes in Swiss hospitals: a correlational
      study.
AB  - BACKGROUND: In the Rationing of Nursing Care in Switzerland Study, implicit
      rationing of care was the only factor consistently significantly associated with
      all six studied patient outcomes. These results highlight the importance of
      rationing as a new system factor regarding patient safety and quality of care.
      Since at least some rationing of care appears inevitable, it is important to
      identify the thresholds of its influences in order to minimize its negative
      effects on patient outcomes. OBJECTIVES: To describe the levels of implicit
      rationing of nursing care in a sample of Swiss acute care hospitals and to
      identify clinically meaningful thresholds of rationing. DESIGN: Descriptive cross
      sectional multi-center study. SETTINGS: Five Swiss-German and three Swiss-French
      acute care hospitals. PARTICIPANTS: 1338 nurses and 779 patients. METHODS:
      Implicit rationing of nursing care was measured using the newly developed Basel
      Extent of Rationing of Nursing Care (BERNCA) instrument. Other variables were
      measured using survey items from the International Hospital Outcomes Study
      battery. Data were summarized using appropriate descriptive measures, and
      logistic regression models were used to define a clinically meaningful rationing
      threshold level. RESULTS: For the studied patient outcomes, identified rationing
      threshold levels varied from 0.5 (i.e., between 0 ('never') and 1 ('rarely') to 2
      ('sometimes')). Three of the identified patient outcomes (nosocomial infections,
      pressure ulcers, and patient satisfaction) were particularly sensitive to
      rationing, showing negative consequences anywhere it was consistently reported
      (i.e., average BERNCA scores of 0.5 or above). In other cases, increases in
      negative outcomes were first observed from the level of 1 (average ratings of
      rarely). CONCLUSIONS: Rationing scores generated using the BERNCA instrument
      provide a clinically meaningful method for tracking the correlates of low
      resources or difficulties in resource allocation on patient outcomes. Thresholds
      identified here provide parameters for administrators to respond to whenever
      rationing reports exceed the determined level of '0.5' or '1'. Since even very
      low levels of rationing had negative consequences on three of the six studied
      outcomes, it is advisable to treat consistent evidence of any rationing as a
      significant threat to patient safety and quality of care.

PMID- 19111307
TI  - Influence of surface modification on protein retention in ion-exchange
      chromatography. Evaluation using different retention models.
AB  - A large number of different stationary phases for ion-exchange chromatography
      (IEC) from different manufacturers are available, which vary significantly in a
      number of chemical and physical properties. As a consequence, binding mechanisms
      may be different as well. In the work reported here, the retention data of model
      proteins (alpha-lactalbumin, beta-lactoglobulin A, bovine serum albumin and
      alcohol dehydrogenase) were determined for three anion-exchange adsorbents based
      on synthetic copolymer beads with differences in the functional group chemistry.
      Fractogel EMD DEAE and Fractoprep DEAE consist of functional groups bound to the
      surface via "tentacles", ToyopearlDEAE by a short linker. Three models which
      describe chromatographic retention were used to analyse the characteristic
      parameters of the protein/stationary-phase interactions. The number of
      electrostatic interaction between the stationary phase and the model proteins,
      the protein specific surface charge densities and the interacting surface of the
      proteins with the adsorptive layer of the chromatographic media depend on the
      surface modification as well as on the molecular mass of the model proteins. In
      general, protein retention of the model proteins on the weak anion exchangers was
      found to be greater if the stationary phase carries tentacles and protein mass is
      above 60 kDa.

PMID- 19111308
TI  - On-tap passive enrichment, a new way to investigate off-flavor episodes in
      drinking water.
AB  - Because taste and odor events in drinking water are often fleeting and
      unpredictable phenomena, an innovative enrichment sampler has been developed to
      trap off-flavor compounds directly at the consumer's tap. The ARISTOT (Advanced
      Relevant Investigation Sampler for Taste & Odor at Tap) consists of a tap adapter
      in which seven polydimethylsiloxane (PDMS) coated stir bars are placed, allowing
      the stir bar sorptive extraction (SBSE) of organic compounds during each tap
      opening. In order to study the efficiency of ARISTOT, a private network pilot
      unit has been constructed in our laboratory, equipped with four faucets in
      parallel, solenoid valves for an automation of the system and a mixing chamber to
      spike drinking water with odorous compounds in order to have homogenously
      smelling water at each tap. After enrichment, the stir bars are taken out, in
      line thermo-desorbed and analyzed by gas chromatography coupled with a mass
      spectrometer. The results showed the high sensitivity of ARISTOT, which was able
      to quickly monitor odorous compounds at the sub ng/L level. A "multishot" method
      was developed to analyze chemicals concentrated on the seven stir bars in only
      one chromatographic run, thereby increasing the sensitivity of the system. Higher
      enrichment factors were obtained under low water flow rates or by using longer
      stir bars and/or stir bars with a higher PDMS film thickness. No significant loss
      of extracted compounds was reported for flow rates between 2 and 4L/min. This
      allowed us to spike the stir bars with an internal standard prior to sampling in
      order to monitor the analytical variations. It was also observed that hot water
      increases the loss of enriched solutes but the quantification can be corrected by
      internal standard addition.

PMID- 19111309
TI  - Combinatorial peptide ligand libraries and plant proteomics: a winning strategy
      at a price.
AB  - The mechanism of action and properties of a solid-phase ligand library made of
      hexapeptides (combinatorial peptide ligand libraries or CPLL), for capturing the
      "hidden proteome", i.e. the low- and very low-abundance proteins constituting the
      vast majority of species in any proteome, as applied to plant tissues, are
      reviewed here. Plant tissues are notoriously recalcitrant to protein extraction
      and to proteome analysis. Firstly, rigid plant cell walls need to be mechanically
      disrupted to release the cell content and, in addition to their poor protein
      yield, plant tissues are rich in proteases and oxidative enzymes, contain
      phenolic compounds, starches, oils, pigments and secondary metabolites that
      massively contaminate protein extracts. In addition, complex matrices of
      polysaccharides, including large amount of anionic pectins, are present. All
      these species compete with the binding of proteins to the CPLL beads, impeding
      proper capture and identification / detection of low-abundance species. When
      properly pre-treated, plant tissue extracts are amenable to capture by the CPLL
      beads revealing thus many new species among them low-abundance proteins. Examples
      are given on the treatment of leaf proteins, of corn seed extracts and of exudate
      proteins (latex from Hevea brasiliensis). In all cases, the detection of unique
      gene products via CPLL capture is at least twice that of control, untreated
      sample.

PMID- 19111310
TI  - Peptide pore accessibility in reversed-phase chromatography.
AB  - The effect of salt or peptide concentration on peptide porosity (i.e. the
      porosity accessible to a given peptide) is investigated on six different reversed
      phase stationary phases. The peptide porosity is found to increase with the local
      concentration of negative charges following a saturation-type function within the
      same porosity boundaries for both cases. This can induce the formation of anti
      Langmuirian peaks in non-adsorbing conditions since the local increase of the
      ionic strength due to the peptide concentration increases the porosity accessible
      to the peptide. This behavior can be well reproduced by the ideal model of
      chromatography assuming non-constant porosity. The acetonitrile adsorption
      isotherm was also measured on all the considered reversed-phase stationary
      phases. A comparison between the stationary phases shows a correlation between
      the amount of acetonitrile accumulated in the pores and the reduced pore
      accessibility for the peptide.

PMID- 19111311
TI  - Solid-phase/supercritical-fluid extraction for liquid chromatography of phenolic
      compounds in freshwater microalgae and selected cyanobacterial species.
AB  - In the present paper a new extraction technique based on the combination of solid
      phase/supercritical-fluid extraction (SPE/SFE) with subsequent reversed-phase
      HPLC is described. The SPE/SFE extractor was originally constructed from SPE
      cartridge incorporated into the SFE extraction cell. Selected groups of benzoic
      acid derivatives (p-hydroxybenzoic, protocatechuic, gallic, vanillic and syringic
      acid), hydroxybenzaldehydes (4-hydroxybenzaldehyde and 3,4-dihydroxybenzaldehyde)
      and cinnamic acid derivatives (o-coumaric, p-coumaric, caffeic, ferulic, sinapic
      and chlorogenic acid) were extracted. Cyclic addition of binary extraction
      solvent system based on methanol:water (1:1, v/v) and methanol/ammonia aqueous
      solution was used for extraction at 40MPa and 80 degrees C. The p-hydroxybenzoic,
      protocatechuic, vanillic, syringic, caffeic and chlorogenic acid; 4
      hydroxybenzaldehyde and 3,4-dihydroxybenzaldehyde were identified by HPLC
      electrospray mass spectrometry in SPE/SFE extracts of acid hydrolyzates of
      microalga (Spongiochloris spongiosa) and cyanobacterial strains (Spirulina
      platensis, Anabaena doliolum, Nostoc sp., and Cylindrospermum sp.). For the
      identification and quantification of the compounds the quasi-molecular ions [M
      H](-) and specific fragments were analysed by quadrupole mass spectrometry
      analyzer. Our analysis showed that the microalgae and cyanobacteria usually
      contained phenolic acids or aldehydes at microg levels per gram of lyophilized
      sample. The proposed SPE/SFE extraction method would be useful for the analysis
      of different plant species containing trace amount of polar fraction of phenols.

PMID- 19111312
TI  - Hyphenation of atmospheric pressure chemical ionisation mass spectrometry to
      supercritical fluid chromatography for polar car lubricant additives analysis.
AB  - Car lubricant additives are added to mineral or synthetic base stocks to improve
      viscosity and resistance to oxidation of the lubricant and to limit wear of
      engines. As they belong to various chemical classes and are added to a very
      complex medium, the base stock, their detailed chromatographic analysis is very
      difficult and time consuming. In a previous paper, it was demonstrated that
      supercritical fluid chromatography (SFC) allows the elution of common low
      molecular-weight additives. Since their total resolution could not be achieved
      owing to the limited peak capacity of packed columns, the hyphenation of
      selective and informative detection methods such as atomic emission detection
      (AED) was required. Further to results obtained in SFC-AED, this work describes
      the hyphenation of SFC to atmospheric pressure chemical ionisation ion trap mass
      spectrometry (MS). SFC-MS hyphenation is detailed: temperature, flow rates of gas
      and mobile phase introduced in the source, position of the restrictor, ionisation
      additives and conditions of autotune are studied. Car lubricant monitoring
      requires negative and positive ionisation modes with or without the addition of
      ionisation auxiliary solvent according to the nature of additives. Moreover, when
      sensitivity is of major concern for a selected additive, the autotuning routine
      of the MS has to be performed in conditions as close as possible to analytical
      conditions, i.e. under subcritical conditions. Unambiguous identification and
      structure elucidation of several additives in formulated car lubricants are also
      presented.

PMID- 19111313
TI  - Surface-modified polystyrene beads as photografting imprinted polymer matrix for
      chromatographic separation of proteins.
AB  - A new and facile fabricating method for lysozyme molecularly imprinted polymer
      beads (lysozyme-MIP beads) in aqueous media was presented. Mesoporous
      chloromethylated polystyrene beads (MCP beads) containing dithiocarbamate
      iniferter (initiator transfer agent terminator) were used as supports for the
      grafting of lysozyme imprinted copolymers with acrylamide and N,N'
      methylenebisacrylamide through surface initiated living-radical polymerization
      (SIP). After the polymerization, a layer of lysozyme-MIP was formed on the MCP
      beads. The SIP allowed an efficient control of the grafting process and
      suppressed solution propagation. Therefore, the obtained lysozyme-MIP beads had a
      large quantity of well-distributed pores on the surface without any visible gel
      formation in solution and were more advantageous comparing with traditional MIPs
      which were prepared by traditionally initiated radical polymerization. The
      obtained composites were characterized by Fourier transform infrared
      spectroscopy, elemental analysis, nitrogen sorption analysis and scanning
      electron microscopy. Chromatographic behaviors of the column packed with lysozyme
      MIP beads exhibited ability in separating lysozyme from competitive protein
      (bovine hemoglobin, bovine serum albumin, ovalbumin or cytochrome c) in aqueous
      mobile phase.

PMID- 19111314
TI  - Vaccines for Mycoplasma diseases in animals and man.
AB  - Vaccines for important mycoplasma diseases, including contagious bovine and
      caprine pleuropneumonia, have been used for centuries, consisting mainly of
      infected tissue or fluids which are inoculated into sites at which the risk of
      severe infection is slight, such as the tail and bridge of the nose.
      Surprisingly, little progress has been made in developing safe, defined and
      protective alternatives, the vaccines today still consisting of mildly attenuated
      strains serially passaged in eggs or in culture. Ill-defined temperature
      sensitive mutants are widely used for mycoplasmoses in poultry despite
      uncertainty about their mode of protection. Inactivated vaccines for enzootic
      pneumonia appear to have improved pig health worldwide, but disease reduction has
      been generally modest. Ironically, attempts to develop subunit preparations have
      often led to exacerbation of disease, particularly in human atypical pneumonia.
      Promising results have been seen in DNA vaccine technology, which has been
      applied to the development of mycoplasma vaccines for porcine enzootic pneumonia,
      but field trials still seem a long way off. No commercial vaccines exist for
      Mycoplasma bovis, despite evidence that this is a major cause of calf pneumonia,
      mastitis and arthritis.

PMID- 19111315
TI  - Pathological findings in dogs with fatal heatstroke.
AB  - Eleven dogs with fatal heatstroke were examined grossly and histopathologically
      post mortem. All showed multi-organ haemorrhagic diathesis with coagulative
      necrosis. Hypaeremia and diffuse oedema were observed in the skin (eight dogs),
      lungs (11), brain (11) and bone marrow (one). Congestion of the splenic pulp (10
      dogs) and hepatic sinusoids (nine) was also noted. Necrosis was observed in the
      mucosa of the small intestine (seven dogs), large intestine (eight), renal
      tubular epithelium (nine), hepatic parenchyma (eight) and brain neural tissue
      (four). The results showed that naturally occurring, fatal canine heatstroke
      induces acute multiple organ lesions affecting most body systems, and suggest
      that the more prevalent lesions include haemorrhagic diathesis, microthrombosis
      and coagulative necrosis. These are probable sequels of hyperthermia-induced
      disseminated intravascular coagulation and systemic inflammatory response
      syndrome, which lead to multi-organ dysfunction and death.

PMID- 19111316
TI  - The effect of inversion on 3- to 5-year-olds' recognition of face and nonface
      visual objects.
AB  - This study compared the effect of stimulus inversion on 3- to 5-year-olds'
      recognition of faces and two nonface object categories matched with faces for a
      number of attributes: shoes (Experiment 1) and frontal images of cars
      (Experiments 2 and 3). The inversion effect was present for faces but not shoes
      at 3 years of age (Experiment 1). Analogous results were found for boys when
      faces were compared with frontal images of cars. For girls, stimulus inversion
      impaired recognition of both faces and cars at 3 to 4 years of age, becoming
      specific to faces only at 5 years of age (Experiments 2 and 3). Evidence
      demonstrates that the ability to extract the critical cues that lead to adults'
      efficient face recognition is selectively tuned to faces during preschool years.

PMID- 19111318
TI  - Iron supplementation of low-income infants: a randomized clinical trial of
      adherence with ferrous fumarate sprinkles versus ferrous sulfate drops.
AB  - OBJECTIVE: To determine whether low-income infants' adherence to nutritional
      supplementation with ferrous fumarate sprinkles was better than that with ferrous
      sulfate drops. STUDY DESIGN: The study was a randomized clinical trial of healthy
      6-month-old infants. Each infant received either a daily packet of sprinkles or a
      dropperful of liquid. Follow-up included alternating telephone and home visits
      biweekly for 3 months. Adherence was defined as high if the infant's caregiver
      reported supplement use on 5 to 7 days during the week before assessment. Side
      effects and caregiver attitude about supplements were secondary outcomes.
      Analyses were conducted using generalized estimating equations and chi(2) and
      Wilcoxon rank-sum tests. RESULTS: A total of 150 of 225 eligible infants were
      enrolled. Adherence to supplementation was generally poor. High adherence ranged
      from 32% to 63% at any assessment in the subjects receiving drops, compared with
      30% to 46% in those receiving sprinkles. The drops group was more likely to have
      at least four assessments with high adherence (22% vs 9.5%; P = .03). Caregivers
      of the drops infants were more likely to report greater than usual fussiness (P <
      .01); however, fussiness had no consistent impact on adherence. CONCLUSIONS: The
      use of ferrous fumarate sprinkles rather than traditional ferrous sulfate drops
      did not improve adherence with daily iron supplementation in low-income infants.

PMID- 19111317
TI  - Epidemiology of necrotizing enterocolitis temporal clustering in two neonatology
      practices.
AB  - OBJECTIVE: To develop a statistical method for defining clusters of necrotizing
      enterocolitis (NEC) cases in the neonatal intensive care unit (NICU). STUDY
      DESIGN: The study group included 2782 infants weighing 401 to 1500 g at birth
      born between 1996 and 2004. NEC was defined as Bell stage II or III. Two
      statistical methods were used to define "disease clusters": a modified scan test
      and a comparison of observed and expected incidence density rates (IDRs) of NEC
      at each NICU. RESULTS: The proportion of infants with NEC was similar in the 2
      NICUs (7.1% vs 7.7%; P = .6), as was the expected IDR of NEC (1.39/1000 patient
      days vs 1.32/1000 patient-days; P = .72). Twelve temporal clusters of NEC were
      identified in the 2 NICUs, representing 18% of 203 total NEC cases during the
      study period. No seasonal/secular trends were noted for NEC rates or identified
      clusters. Potential NEC clusters of > or =3 cases at either NICU had a >75%
      likelihood of being a true NEC cluster. CONCLUSIONS: No operational definition of
      NEC cluster exists. This study introduces methods to use in prospective
      surveillance and to guide studies investigating etiologic relevance. Using the
      proposed methods, statistically significant clusters (ie, potential outbreaks) of
      NEC within NICUs can be identified early, providing an opportunity for early
      implementation of cluster investigation protocols.

PMID- 19111319
TI  - Pediatric stroke: do clinical factors predict delays in presentation?
AB  - OBJECTIVE: To explore associations between age, clinical presentation, or
      predisposing conditions and delayed diagnosis of arterial ischemic stroke. STUDY
      DESIGN: This was a retrospective chart review of children admitted to tertiary
      care medical centers in San Diego County between 1995 and 2000. Inpatient charts
      were screened by ICD-9 codes for stroke, cerebrovascular anomalies, hemiplegia,
      and migraine. RESULTS: Time of presentation for medical evaluation did not differ
      by age group, clinical presentation, or risk factors. There was no relationship
      between time of presentation and Glasgow Outcome Score. Only 24% (9/37) of the
      patients with ischemic stroke presented for clinical evaluation within 6 hours
      after onset of symptoms, and an additional 41% (13/37) presented within the first
      24 hours. Children who initially presented with altered mental status were more
      likely to die than those with other initial presentations (odds ratio = 9.94; 95%
      confidence interval = 2.05 to 47.9), but none of the 16 children who presented
      with hemiparesis died (P = .01). CONCLUSION: Time of presentation was not related
      to the clinical factors studied. Early recognition of stroke in children is an
      important goal for families and health care providers.

PMID- 19111320
TI  - Prevalence and long-term course of macro-aspartate aminotransferase in children.
AB  - OBJECTIVES: To investigate the prevalence, association with clinical conditions,
      and long-term course of macro-aspartate aminotransferase (macro-AST). STUDY
      DESIGN: Forty-four children with an isolated elevation of serum AST were screened
      for macro-AST with electrophoresis and % polyethylene glycol (PEG) precipitable
      activity (PPA). RESULTS: All children were healthy, except they had elevated AST
      values. Seventeen children (38.6%) were macro-AST-positive. They had higher AST
      values than the 27 children who were macro-AST-negative (P = .001). Values <67.1%
      PPA and >82.2% PPA were associated with a very low probability of being macro-AST
      positive and macro-AST-negative, respectively. Thirty-eight children underwent
      clinical and laboratory follow-up (mean, 4.7 +/- 3.8; range, 1-16 years). All
      remained symptom-free. AST levels decreased significantly only in children who
      were macro-AST-negative (P = .006). Macroenzyme persisted in 6 of the 9 children
      who were macro-AST-positive after 6.0 +/- 4.1 years. CONCLUSIONS: Macro-AST was
      present in more than one-third of children with an isolated increase of AST
      levels. The lack of pathological correlates in a long period argues for the
      benign nature of this phenomenon in childhood. We suggest that our %PPA
      thresholds can be used as a screening test and that electrophoresis be reserved
      for confirming positive screen test results and cases in which %PPA levels are of
      intermediate discriminant accuracy.

PMID- 19111321
TI  - Adipose tissue infiltration of skeletal muscle in children with cerebral palsy.
AB  - OBJECTIVE: To determine whether children with quadriplegic cerebral palsy (QCP)
      have a greater adipose tissue (AT) infiltration of skeletal muscle than typically
      developing children (12/group and 5-14 years). STUDY DESIGN: Cross-sectional area
      (CSA) of AT and muscle in the midthigh were assessed with magnetic resonance
      imaging. Physical activity was assessed with an activity monitor. RESULTS:
      Children with QCP had 2.3-fold higher intermuscular AT CSA and 51% lower muscle
      CSA in the midthigh than control subjects. Midthigh intermuscular, subfascial,
      and subcutaneous AT CSA adjusted for midthigh muscle CSA were higher in children
      with QCP (all P < .05). Moreover, the proportion of intermuscular AT CSA and
      subfascial AT CSA relative to subcutaneous AT CSA in the midthigh were 2.5-fold
      and 1.8-fold higher in children with QCP than control subjects (all P < .05).
      Children with QCP also had 70% fewer physical activity counts, which was
      inversely related to intermuscular AT CSA (r = -0.76) and subfascial AT CSA (r = 
      0.63) adjusted for muscle CSA in the midthigh of children with QCP (both P <
      0.05), but not in control subjects. CONCLUSION: Children with QCP have a greater
      AT infiltration of skeletal muscle than typically developing children, which is
      related to their low level of physical activity.

PMID- 19111323
TI  - LCSGJ-T classification, 6th or 5th edition TNM staging did not independently
      predict the long-term prognosis of HBV-related hepatocellular carcinoma after
      radical hepatectomy.
AB  - BACKGROUND: The 6th edition tumor-node-metastasis (TNM) staging (TNM-6) for
      hepatocellular carcinoma (HCC) was recommended. Besides, Liver Cancer Study Group
      of Japan (LCSGJ)-T classification has been recently proposed. However, these
      newly established staging systems should be further verified in different
      subgroups of HCC patients. The current study mainly aimed to validate the
      predictive power of these novel criteria in a cohort of patients with hepatitis B
      virus-related HCC after radical hepatectomy. As a control, the 5th edition TNM
      staging (TNM-5) was also evaluated. METHODS AND MATERIALS: Clinicopathological
      and follow-up data of consecutive 142 patients with HBV-related HCC undergoing
      radical hepatectomy were reviewed. The impact of variables on prognosis was
      determined by uni- and multivariate analyses. RESULTS: By univariate analysis,
      LCSGJ-T classification, TNM-6, and TNM-5 were almost significantly prognostic,
      except for TNM-5 for disease-free survival. Meanwhile, tumor size>or=5 cm, alpha
      fetoprotein>400 ng/mL, high Edmondson-Steiner grade, presence of microvascular
      invasion, portal vein tumor thrombosis, satellite nodule, and resection
      margin<or=1 cm were also associated with decreased overall or disease-free
      survival. Multivariate analysis, including aforementioned factors, suggested that
      Edmondson-Steiner grade was the sole independent prognosticator for both overall
      and disease-free survival, when LCSGJ-T classification, TNM-6, and TNM-5 were
      entered, respectively. However, all 3 staging systems lost their predictive
      potentials in multivariate analysis. CONCLUSIONS: LCSGJ-T classification, TNM-6,
      and TNM-5 were not revealed to be independently prognostic in patients with HBV
      related HCC after radical hepatectomy. Therefore, these staging criteria,
      especially the newly developed ones, call for more support in many subsets of HCC
      patients.

PMID- 19111324
TI  - Implication of protein kinase A for a hepato-protective mechanism of milrinone
      pretreatment.
AB  - BACKGROUND: We have previously reported that an increase of adenosine 3',5'
      cyclic monophosphate (cAMP) in liver tissue after an administration of milrinone,
      a phosphodiesterase-3 inhibitor attenuates hepatic warm ischemia-reperfusion
      injury. The aim of this study was to determine whether cAMP-dependent protein
      kinase (protein kinase A) activation was involved in the milrinone-induced
      hepatoprotective effect on an ischemia-reperfusion injury in an in vivo model.
      MATERIALS AND METHODS: Male Lewis rats were allocated into 3 groups. In Group M,
      milrinone was administrated before ischemia; in Group I, a protein kinase A
      inhibitor, adenosine 3',5'-cyclic monophosphorothioate, 8-bromo-, Rp-isomer,
      sodium salt (Rp-8-Br-cAMPS), was injected prior to the administration of
      milrinone; and in Group C, the control group, there was no pretreatment. After
      pretreatment, all rats were exposed to a 45-min total hepatic inflow occlusion.
      RESULTS: After milrinone administration, liver cAMP concentrations and protein
      kinase A activity ratios were elevated. They protected the liver from ischemia
      reperfusion injury. Rp-8-Br-cAMPS suppressed protein kinase A activation without
      affecting cAMP elevating responses to milrinone. Compared with Group C,
      hepatocellular necrosis, neutrophil infiltration, and congestion were
      ameliorated, and serum tumor necrosis factor-alpha, aspartate aminotransferase,
      alanine aminotransferase, and lactate dehydrogenase levels were significantly
      suppressed in Group M. Rp-8-Br-cAMPS canceled this effect, showing histological
      damages in Group I as severe as in Group C. The levels of tumor necrosis factor
      alpha, aspartate aminotransferase, alanine aminotransferase, and lactate
      dehydrogenase were the same in Groups C and I. CONCLUSIONS: Activation of protein
      kinase A might play an important role in the mechanism of milrinone-induced
      ischemic tolerance in the liver.

PMID- 19111325
TI  - Effects of thyroid hormone on the adaptation in short bowel syndrome.
AB  - BACKGROUND: Thyroid hormone acts on structural and functional maturation of the
      mammalian small intestine, mitochondrial pathways, and several protein-gene
      interactions. Therefore, it is one of the most important regulators of intestinal
      epithelial differentiation. The aim of the study was to evaluate the effects of
      thyroid hormone on the adaptation in an experimental model of short bowel
      syndrome. METHODS: Rats were divided into three groups: sham (bowel transection
      and anastomosis), short bowel syndrome-saline (75% bowel resection and
      anastomosis), and short bowel syndrome-thyroid hormone (75% bowel resection and
      anastomosis, and was administered triiodothyronine). The evaluation of adaptation
      parameters, histopathological and biochemical analysis were performed in all
      groups. RESULTS: Triiodothyronine treatment resulted in a significant increase in
      adaptation parameters, villus height-crypt depth, and enterocyte proliferation,
      whereas significant decrease was seen in apoptotic index in jejunum. Enterocyte
      proliferation and most of the adaptation parameters changed significantly in
      ileum following the treatment with triiodothyronine as in jejunum. The changes in
      ileal villus height-crypt depth and apoptotic index were not statistically
      significant. Serum levels of free triiodothyronine were lower in the short bowel
      syndrome-saline group. CONCLUSIONS: Our results suggest that thyroid hormone
      treatment in the hypothyroid phase of SBS enhances intestinal adaptive response.

PMID- 19111326
TI  - The utilization of a biopsy needle to obtain small muscle tissue specimens to
      analyze the gene and protein expression.
AB  - Recent analytical methods such as real-time polymerase chain reaction (PCR) and
      Western blotting have now enabled us to analyze the gene and protein expression
      from small amounts of tissue. A fine needle muscle biopsy is thus expected to
      obtain a minimally sufficient amount of skeletal muscle to make a successful
      analysis. As a result, we used this fine needle muscle biopsy technique to obtain
      muscle tissue specimens from the vastus lateral muscle in 40 participants. The
      amount of tissue obtained by the fine needle was 5.2 +/- 3.2 mg (mean +/-
      standard deviation). The total RNA extracted was 3.0 +/- 1.4 microg and the total
      protein extracted was 2203 +/- 1541 microg. Furthermore, the skeletal muscle
      tissue specimens obtained by the regular needle technique and blood sample were
      used as the control. Those specimens were used to measure the gene expression of
      beta-myosin heavy chain slow (beta-MHC slow) by real-time PCR and the protein
      expression of monocalboxylate transporter 1 (MCT-1) by Western blotting. Beta-MHC
      slow gene expression was detected in both samples obtained by a fine and a
      regular needle biopsy, but not in a blood sample. Furthermore, the MCT-1 protein
      was detected in samples obtained by a fine needle muscle biopsy. These results
      indicated that the fine needle muscle biopsy is therefore a useful technique to
      obtain skeletal muscle specimens at least to analyze the gene and protein
      expression.

PMID- 19111322
TI  - Maternal age, multiple birth, and extremely low birth weight infants.
AB  - OBJECTIVES: To compare the rates of adverse neurodevelopmental outcome or death
      at 18 to 22 months among extremely low birth weight (ELBW) infants born to
      mothers >or=4 0 years to the corresponding rates among infants of younger
      mothers. STUDY DESIGN: Prospective evaluation of ELBW infants to quantify the
      relative risks of maternal age and multiple birth for death or adverse
      neurodevelopmental outcome. RESULTS: The sample consisted of 14 671 live ELBW
      births divided into maternal age groups: <20, 20 to 29, 30 to 39, and >or= 40
      years. Of infants born to mothers >or= 40 years, 20% were multiples. Mothers >or=
      40 years had high rates of obstetric interventions and medical morbidities
      compared with mothers <40 years. ELBW live births of mothers >or= 40 years were
      22% more likely to survive and had a 13% decreased risk of neurodevelopmental
      impairment or death compared with mothers <20. Multiple birth, however, was
      associated with a 10% greater risk of neurodevelopmental impairment or death.
      CONCLUSION: Although mothers >or= 40 years had high pregnancy-related
      morbidities, we found no overall increased risk of the composite outcome of death
      or NDI. Multiple birth, however, was a predictor of all adverse outcomes
      examined, regardless of maternal age.

PMID- 19111327
TI  - Differential regulation of aortic growth in male and female rodents is associated
      with AAA development.
AB  - BACKGROUND: The objective was to examine effects of gonadal hormone manipulation
      on aortic diameter and macrophage infiltration in rodents during abdominal aortic
      aneurysm (AAA) formation. METHODS: Experiment 1: 17-beta estradiol and
      testosterone pellets were implanted in male (ME) and female (FT) rats. No pellet
      was implanted in shams (MES, FTS). Experiment 2: Testes and ovaries were removed
      from males (MO) and females (FO), respectively. No organs were removed from shams
      (MOS, FOS). Experiment 3: Male and female rats were orchiectomized and
      oophorectomized, respectively. Four weeks post-castration, testosterone (MOT) and
      17-beta estradiol (FOE) pellets were implanted. Shams underwent castration, but
      no pellet was implanted (MOTS, FOES). All rats underwent infrarenal aortic
      infusion with elastase postimplantation/postcastration. Diameters were measured
      on postoperative d 14. Tissue was stained for macrophages by
      immunohistochemistry. RESULTS: Diameter (P = 0.046) and macrophage counts (P =
      0.014) decreased in ME compared with shams, but not in females treated with
      testosterone (FT). Diameter (P = 0.019) and macrophage infiltration (P = 0.024)
      decreased in MO compared with shams, but not in FO. Diameter increased in MOT
      compared with MOTS (P = 0.033), but decreased in FOE compared with FOES (P =
      0.002). Macrophages decreased in FOE compared with FOES (P = 0.002). CONCLUSION:
      This study documents a decrease in AAA diameter in males treated with estrogen or
      undergoing orchiectomy, but no changes in females treated with testosterone or
      undergoing oophorectomy; and an increase in diameter in MOT and a decrease in
      FOE. These data suggest that gonadal hormones differentially regulate AAA growth
      in association with changes in macrophages.

PMID- 19111328
TI  - Polychlorinated biphenyls in sediments of selected coastal environments in
      northern Morocco.

PMID- 19111329
TI  - Fate of beta blockers and psycho-active drugs in conventional wastewater
      treatment.
AB  - The removal of beta blockers and psycho-active drugs was investigated in a
      representative conventional German WWTP by long-term measurement campaigns along
      different biological treatment processes. The activated sludge treatment with an
      elevated SRT of 18 d was the only process which led to a significant removal of
      certain beta blockers and psycho-active drugs. The removal efficiency was below
      60% for all compounds except for the natural opium alkaloids codeine and morphine
      being removed by more than 80%. Primary biological transformation and sorption
      onto sludge as the main removal mechanisms were examined in lab-scale batch
      experiments. Sorption onto activated sludge was found to be negligible (<3%). The
      biological transformation could be described by pseudo-first order kinetics and
      the transformation constants k(biol) were used to predict the removal of beta
      blockers and psycho-active drugs in an activated sludge unit with a model. For
      most compounds the removal efficiencies measured on the full-scale WWTP were
      within the 95% confidence intervals predicted by the model. The results from full
      scale measurements and modeling indicate that biological transformation in the
      nitrification tank together with parameters such as the sludge retention time and
      the temperature is crucial regarding the biological transformation of beta
      blockers and psycho-active drugs in conventional WWTPs.

PMID- 19111330
TI  - Bacterial reduction in genotoxicity of Direct Red 28 dye.
AB  - Direct Red 28 (DR28) is a benzidine-based azo dye widely used in several
      countries. It has also been a subject of intense research for its anti-prion
      activity. Like other benzidine-based azo dyes, it is also carcinogenic and toxic.
      However, there are very few studies addressing its detoxification. In the present
      study, a Bacillus velezensis strain was used for detoxification of DR28. Toxicity
      was checked by a battery of highly sensitive genotoxicity assays like comet
      assay, DNA ladder formation, terminal deoxynucleotidyl transferase-mediated dUTP
      nick-end labeling assay and flow cytometric Annexin V binding assay. HL-60 cell
      line was used as the test system. All the assays showed an initial increase in
      toxicity upon biodegradation due to release of mutagenic products, like benzidine
      and 4-aminobiphenyl, from the dye. These intermediates caused significant DNA
      damage and induced apoptosis in HL-60 cells. Then the culture degraded these
      mutagenic intermediates, due to which the toxicity was reduced gradually, finally
      resulting in nearly complete detoxification.

PMID- 19111331
TI  - The early Upper Paleolithic occupations at Ucagizli Cave (Hatay, Turkey).
AB  - This paper summarizes results from excavations at Ucagizli Cave (Hatay, Turkey)
      between 1999 and 2002 and 2005. This collapsed karstic chamber contains a
      sequence of early Upper Paleolithic deposits that span an interval between
      roughly 29,000 and 41,000 (uncalibrated) radiocarbon years BP. Lithic assemblages
      can be assigned to two major chronostratigraphic units. The earliest assemblages
      correspond with the Initial Upper Paleolithic, whereas the most recent ones fit
      within the definition of the Ahmarian. Substantial assemblages of stone tools,
      vertebrate faunal remains, ornaments, osseous artifacts, and other cultural
      materials provide an unusually varied picture of human behavior during the
      earliest phases of the Upper Paleolithic in the northern Levant. The sequence at
      Ucagizli Cave documents the technological transition between Initial Upper
      Paleolithic and Ahmarian, with a high degree of continuity in foraging and
      technological activities. The sequence also documents major shifts in
      occupational intensity and mobility.

PMID- 19111332
TI  - Increased asthma and respiratory symptoms in children exposed to petrochemical
      pollution.
AB  - BACKGROUND: Epidemiologic studies show statistical associations between levels of
      air pollutants and respiratory outcomes. OBJECTIVE: We sought to determine the
      effects of exposure to petrochemical pollution on the respiratory health of
      children. METHODS: Children aged 6 to 12 years living close to the petrochemical
      plants in La Plata, Argentina (n = 282), were compared with those living in a
      region with exposure to heavy traffic (n = 270) or in 2 relatively nonpolluted
      areas (n = 639). Parents answered a validated questionnaire providing health and
      demographic data. A random sample (n = 181) had lung function measured.
      Particulate matter and outdoor and indoor volatile organic compound levels were
      measured during 4-week study periods and reported as overall means for each study
      area. RESULTS: Children living near the petrochemical plant had more asthma
      (24.8% vs 10.1% to 11.5%), more asthma exacerbations (6.7 vs 2.9-3.6 per year),
      more respiratory symptoms (current wheeze, dyspnea, nocturnal cough, and
      rhinitis), and lower lung function (>13% decrease in FEV(1) percent predicted)
      than those living in other regions. Length of residence in the area was a
      significant risk factor, but age, sex, body mass index, proximity to busy roads
      and other nonpetrochemical industries, length of breast-feeding, and
      socioeconomic and demographic characteristics of children or their families were
      not. CONCLUSION: Exposure to particulate matter and volatile organic compounds
      arising from petrochemical plants but not from high traffic density was
      associated ith worse respiratory health in children.

PMID- 19111333
TI  - AluI polymorphism of the bovine growth hormone (GH) gene, resumption of ovarian
      cyclicity, milk production and loss of body condition at the onset of lactation
      in dairy cows.
AB  - Relationships among GH genotype (AluI polymorphism), parity, metritis and
      interval from calving to first ovulation, milk production and body condition
      score (BCS) loss were determined in dairy cows (n=307) on four large-scale farms
      in Hungary. Cows with systemic signs of puerperal metritis or mastitis were
      excluded. Time of the first postpartum (PP) ovulation was obtained from milk
      progesterone profiles. Based on GH genotype determination, groups of leucine
      homozygous cows (n=246) and valine allele carriers (n=61) were formed. All
      animals became cyclic during the study period. The average interval to first
      ovulation was 27.6+/-0.69-d PP (mean+/-S.D.). Genotype had no effect on the
      commencement of ovarian cyclicity. First ovulation occurred sooner after calving
      in pluriparous than in primiparous cows. The greater BCS loss cows had during the
      first 30-d PP, the longer they took to resume cyclic ovarian function. The
      interval from calving to first ovulation was substantially affected by farm, but
      not by mild cases of puerperal metritis. Genotype was not related to cumulative
      30-d milk yield or BCS loss after calving. Primiparous cows had lower milk yield
      than pluriparous ones. Cows with metritis lost more body condition than healthy
      individuals in the first month postpartum. We concluded that, under field
      conditions, AluI polymorphism of the bovine GH gene had no effect on the interval
      from calving to first ovulation and could not be directly related to differences
      in milk yield and to the extent of BCS loss during the first month after calving
      in Holstein-Friesian cows.

PMID- 19111334
TI  - Alternative photoinitiator system reduces the rate of stress development without
      compromising the final properties of the dental composite.
AB  - OBJECTIVES: Stress development during the polymerization process continues to be
      a major factor that limits predictability and longevity of resin composite
      restorations. This study evaluated the effect of the photoinitiator type on the
      maximum rate of polymerization (R(p)(max)), stress development (final stress and
      maximum rate, R(stress)(max)), degree of conversion (DC) and cross-link density
      (CLD) of materials containing camphorquinone (CQ), phenylpropanedione (PPD) or
      CQ/PPD. MATERIALS AND METHODS: R(p)(max) was evaluated via differential scanning
      calorimetry (DSC). Contraction force measurement was assessed with a single
      cantilever device for 5min. The samples were subsequently tested by infrared
      spectroscopy (FTIR) to evaluate the DC. After, samples were soaked in ethanol to
      evaluate the swelling coefficient (alpha) as a way to estimate the CLD. The
      results were analyzed by one-way ANOVA and Tukey's test (p=0.05). RESULTS: CQ
      showed the highest R(p)(max) and R(stress)(max). PPD produced the lowest DC and
      the highest alpha. The mixture CQ/PPD produced statistically lower R(p)(max) and
      R(stress)(max) than CQ alone, but similar DC and CLD. CONCLUSION: CQ/PPD reduced
      the R(p)(max) and R(stress)(max) without a reduction in DC and CLD. Therefore,
      the use of alternative photoinitiator systems could be a promising way to reduce
      the stress developed during the composite's polymerization without affecting the
      final properties.

PMID- 19111335
TI  - Effects of residual ethanol on the rate and degree of conversion of five
      experimental resins.
AB  - OBJECTIVES: This study examined the extent of ethanol retention in five comonomer
      blends of experimental methacrylate-based dental adhesives, containing (10, 20,
      or 30 wt.%) ethanol, after solvent evaporation, as well as observing the effect
      of residual ethanol and exposure duration on degree of conversion (DC). The null
      hypothesis that was tested was that residual, unevaporated ethanol has no effect
      on the rate or extent of DC of polymerized adhesive resins. METHODS: A known mass
      of each mixture was placed in glass wells and evaporated for 60s. The mass of the
      mixtures before and after evaporation was measured, allowing calculation of the
      gravimetric ethanol loss/retention. RESULTS: The concentration of retained
      ethanol increased significantly with ethanol concentration (p<0.01): 1.1-1.9
      mole/L for 10% ethanol/90% comonomers, 2.2-3.5 mole/L for 20% ethanol, and 2.6
      3.7 mole/L for 30% ethanol/70% comonomers. As ethanol is evaporated from solvated
      comonomer mixtures, the molar concentration of comonomers increases, reducing the
      vapor pressure of the remaining ethanol. Thus, the fractional loss of ethanol
      solvent decreases as the comonomer concentration increases. The DC of 10, 20, and
      30 wt.% ethanol blends increased with ethanol concentration in four of the five
      experimental resins (p<0.05), increasing by 30-45% when 10 or 20 wt.% ethanol was
      added to neat resins, regardless of exposure duration. Depending on the resin
      system, inclusion of 30% ethanol lowered DC at 20s but increased DC after 40-60s
      of light exposure. SIGNIFICANCE: Since 10 and 20 wt.% ethanol-resin blends
      increased the DC of solvated resins by 30-45% over neat resins, the test null
      hypothesis is rejected. Even with prolonged evaporation, 4-9% residual ethanol
      concentration can remain in 90/10 (wt./wt.) comonomer-ethanol mixtures. This is
      thought to be because comonomers lower the vapor pressure of ethanol. This amount
      of residual ethanol facilitates DC but lowers the rate of polymerization.

PMID- 19111336
TI  - Tidal height influences the levels of enzymatic antioxidant defences in Mytilus
      edulis.
AB  - We investigated the potential variability of enzymatic antioxidant activities in
      blue mussels Mytilus edulis from a single intertidal population but living at
      different tidal heights. Activity levels of antioxidant enzymes (Cu/Zn superoxide
      dismutase, catalase, glutathione peroxidase, glutathione reductase, glutathione
      transferase) were measured in the gills and digestive gland of mussels sampled at
      high shore (HS, air-exposure>6h/12h) and low shore (LS, air-exposure<2h/12h) of
      an intertidal zone (Yport, Normandie, France) for two consecutive autumns. In
      both tissues, levels of each enzymatic activity (except GST) were clearly higher
      in HS mussels than in LS for the two years. These results suggest an ability to
      acclimate the enzymatic antioxidant defences to the degree of undergone stress,
      confirming the importance of environmental conditions in the antioxidant
      responses. Therefore, the location of organisms on the shore should be taken into
      account in sampling for ecotoxicological studies.

PMID- 19111337
TI  - delta(15)N and delta(13)C in the Mondego estuary food web: seasonal variation in
      producers and consumers.
AB  - Assessments of temporal variation in stable carbon and nitrogen ratios were used
      to examine seasonal trends of the water column and benthic food webs in the
      Mondego estuary (Portugal). There was a marked seasonality in weather and water
      column conditions, including nutrient supply and chlorophyll concentrations. In
      spite of the pronounced environmental changes, we found little evidence of
      seasonal variation in delta(13)C and delta(15)N of producers and consumers in the
      Mondego estuary, with a few notable exceptions. Nitrogen isotope ratios in
      macrophytes (Zostera noltii, Ulva sp., Enteromorpha sp., and Gracilaria sp.), and
      in two grazers (Idotea chelipes and Lekanesphaera levii) increased during late
      summer, with the highest delta(15)N values being measured in July, during a
      period of elevated temperatures and drought, which may have favored high rates of
      denitrification and heavier delta(15)N values. The results suggest that stable
      isotope values from macrophytes and selected grazers are useful as tracers of
      seasonal changes in nitrogen inputs into estuaries, and that those of consumers
      reflect other factors beyond seasonal variations in N and C sources.

PMID- 19111338
TI  - Mechanical properties of completely autologous human tissue engineered blood
      vessels compared to human saphenous vein and mammary artery.
AB  - We have previously reported the initial clinical feasibility with our small
      diameter tissue engineered blood vessel (TEBV). Here we present in vitro results
      of the mechanical properties of the TEBVs of the first 25 patients enrolled in an
      arterio-venous (A-V) shunt safety trial, and compare these properties with those
      of risk-matched human vein and artery. TEBV average burst pressures (3490+/-892
      mmHg, n=230) were higher than native saphenous vein (SV) (1599+/-877 mmHg, n=7),
      and not significantly different from native internal mammary artery (IMA) (3196+/
      1264 mmHg, n=16). Suture retention strength for the TEBVs (152+/-50 gmf) was also
      not significantly different than IMA (138+/-50 gmf). Compliance for the TEBVs
      prior to implantation (3.4+/-1.6%/100 mmHg) was lower than IMA (11.5+/-3.9%/100
      mmHg). By 6 months post-implant, the TEBV compliance (8.8+/-4.2%/100 mmHg, n=5)
      had increased to values comparable to IMA, and showed no evidence of dilation or
      aneurysm formation. With clinical time points beyond 21 months as an A-V shunt
      without intervention, the mechanical tests and subsequent lot release criteria
      reported here would seem appropriate minimum standards for clinical use of tissue
      engineered vessels.

PMID- 19111340
TI  - The two distinctive metal ion binding domains of the wheat metallothionein Ec-1.
AB  - Metallothioneins are small cysteine-rich proteins believed to play a role, among
      others, in the homeostasis of essential metal ions such as Zn(II) and Cu(I).
      Recently, we could show that wheat E(c)-1 is coordinating its six Zn(II) ions in
      form of metal-thiolate clusters analogously to the vertebrate metallothioneins.
      Specifically, two Zn(II) ions are bound in the N-terminal and four in the C
      terminal domain. In the following, we will present evidence for the relative
      independence of the two domains from each other with respect to their metal ion
      binding abilities, and uncover three intriguing peculiarities of the protein.
      Firstly, one Zn(II) ion of the N-terminal domain is relative resistant to
      complete replacement with Cd(II) indicating the presence of a Zn(II)-binding site
      with increased stability. Secondly, the C-terminal domain is able to coordinate
      an additional fifth metal ion, though with reduced affinity, which went
      undetected so far. Finally, reconstitution of apoE(c)-1 with an excess of Zn(II)
      shows a certain amount of sub-stoichiometrically metal-loaded species. The
      possible relevance of these finding for the proposed biological functions of
      wheat E(c)-1 will be discussed. In addition, extended X-ray absorption fine
      structure (EXAFS) measurements on both, the full-length and the truncated
      protein, provide final evidence for His participation in metal ion binding.

PMID- 19111339
TI  - PLGA-lecithin-PEG core-shell nanoparticles for controlled drug delivery.
AB  - Current approaches to encapsulate and deliver therapeutic compounds have focused
      on developing liposomal and biodegradable polymeric nanoparticles (NPs),
      resulting in clinically approved therapeutics such as Doxil/Caelyx and Genexol
      PM, respectively. Our group recently reported the development of biodegradable
      core-shell NP systems that combined the beneficial properties of liposomal and
      polymeric NPs for controlled drug delivery. Herein we report the parameters that
      alter the biological and physicochemical characteristics, stability, drug release
      properties and cytotoxicity of these core-shell NPs. We further define scalable
      processes for the formulation of these NPs in a reproducible manner. These core
      shell NPs consist of (i) a poly(D,L-lactide-co-glycolide) hydrophobic core, (ii)
      a soybean lecithin monolayer, and (iii) a poly(ethylene glycol) shell, and were
      synthesized by a modified nanoprecipitation method combined with self-assembly.
      Preparation of the NPs showed that various formulation parameters such as the
      lipid/polymer mass ratio and lipid/lipid-PEG molar ratio controlled NP physical
      stability and size. We encapsulated a model chemotherapy drug, docetaxel, in the
      NPs and showed that the amount of lipid coverage affected its drug release
      kinetics. Next, we demonstrated a potentially scalable process for the
      formulation, purification, and storage of NPs. Finally, we tested the
      cytotoxicity using MTT assays on two model human cell lines, HeLa and HepG2, and
      demonstrated the biocompatibility of these particles in vitro. Our data suggest
      that the PLGA-lecithin-PEG core-shell NPs may be a useful new controlled release
      drug delivery system.

PMID- 19111354
TI  - Thromboxane and isoprostanes as inflammatory and vasoactive mediators in black
      walnut heartwood extract induced equine laminitis.
AB  - Inflammation and vascular dysfunction occur concurrently during the prodromal
      stages of equine laminitis. The aim of this study was to provide insights into
      the role that thromboxane and isoprostanes may play in the development of black
      walnut heartwood extract (BWHE)-induced laminitis. Horses were divided into two
      groups, either control or BWHE-administered horses. Plasma concentrations of
      thromboxane increased transiently after administration of BWHE and coincided with
      the nadir in white blood cell counts, whereas plasma concentrations of iso
      prostaglandin PGF(2alpha) (iso-PGF(2alpha)) did not change in either group. At
      12h (for the control group) or Obel grade 1 laminitis (for the BWHE group) the
      horses were euthanized and laminar tissue collected. Laminar arteries and veins
      were used in functional studies with vasoconstrictor substances and tissue
      samples were used for the determination of laminar iso-PGF(2alpha)
      concentrations. Laminar tissue concentrations of iso-PGF(2alpha) were
      significantly greater in BWHE horses when compared to control horses. In parallel
      studies concentrations of iso-PGF(2alpha) in laminar tissue samples obtained 1.5
      and 3h after administration of BWHE were indistinguishable from those for control
      horses at 3 or 12h after administration of an equal volume of water. Laminar
      vessel constrictor responses to either a thromboxane mimetic (U46619), iso
      prostaglandin PGE(2) (iso-PGE(2)) or iso-PGF(2alpha) were determined using small
      vessel myographs. In some vessels, the effects of putative prostanoid and
      thromboxane receptor antagonists, SQ 29,548, SC-19220 and AH 6809, upon
      contractile responses were determined. In control horses, U46619, iso-PGF(2alpha)
      and iso-PGE(2) more potently and efficaciously constricted laminar veins when
      compared to laminar arteries. Responses of laminar veins from BWHE horses to iso
      PGE(2) were similar to those of laminar veins from control horses, whereas iso
      PGF(2alpha) elicited significantly greater responses in laminar veins from BWHE
      horses when compared to controls. In contrast, responses to U46619 were smaller
      in laminar veins isolated from BWHE horses when compared to those in laminar
      veins from control horses. In the presence of SQ 29,548, iso-PGF(2alpha) elicited
      a small dilation in laminar veins from control horses, which was not apparent in
      laminar veins from BWHE horses. These results are consistent with both systemic
      and local inflammatory events occurring during the prodromal stages of BWHE
      induced laminitis. Because laminar veins are sensitive to thromboxane and
      isoprostanes, these substances may act as conduits between the inflammatory and
      vascular events occurring in laminitis and may be therapeutic targets for this
      crippling condition.

PMID- 19111355
TI  - Differential microglial activation between acute stress and lipopolysaccharide
      treatment.
AB  - Acute stress was demonstrated to induce morphological microglial activation in
      several brain regions including the midbrain periaqueductal gray (PAG), an area
      that plays important roles in behavioral responses to uncontrollable stress,
      threat, anxiety, and pain. To determine whether neuronal activation may be
      involved in the stress-induced microglial activation, the present study
      investigated the correlation between neuronal activity measured as c-Fos
      expression and morphological microglial activation in the PAG. Acute stress was
      followed by morphological activation of microglia and increased c-Fos expression
      in the PAG but not in the surrounding midbrain. Double immunohistochemistry and
      topological analysis demonstrated that microglial activation occurred adjacent to
      responsive neurons. By contrast, lipopolysaccharide (LPS) treatment induced
      microglial activation even in the absence of neuronal responses in the PGA as
      well as in the rest of the midbrain. These findings suggest that the mechanism of
      microglial activation during stress may differ from those of infection or
      inflammation. It also indicates that the neuronal cells expressing c-Fos protein
      may play some roles to trigger microglial activation.

PMID- 19111356
TI  - Amphibian toxicology. Editorial.

PMID- 19111357
TI  - The effect of water chemistry on the acute toxicity of nickel to the cladoceran
      Daphnia pulex and the development of a biotic ligand model.
AB  - The goal of this study was to evaluate the influence of water chemistry
      parameters on the acute toxicity of waterborne Ni to Daphnia pulex in soft waters
      and using this information to develop a biotic ligand model. The effects of Ca,
      Mg, Na, K, Cl, pH (two differently buffered sets) and natural organic matter
      (NOM) from two sources were evaluated in standardized 48h acute toxicity tests.
      Increases in Ca2+ had a protective effect on Ni toxicity, suggesting that this
      ion competes with Ni at the site of biological uptake. Increased waterborne Mg2+
      also reduced Ni toxicity, but to a lesser degree compared with Ca2+. EC50 values
      increased at higher pH when the organic buffer 3-morpholinepropanesulfonic acid
      was used to adjust test pH, however in tests series where pH was varied using
      HCO(3)(-) the results were equivocal. Other testing showed that Na, K and Cl did
      not influence the toxicity response of D. pulex to Ni. Complexation of Ni by NOM
      reduced toxicity but Nordic Reservoir NOM was much more protective compared to
      Suwannee River NOM. Geochemical modeling of organic matter complexation of Ni was
      done using the HydroQual Biotic Ligand Model (BLM ver. 2.3.3; research mode) and
      the Windermere Humic Aqueous Model (WHAM ver 6.0). Results showed dramatic
      differences between the two models in dissolved organic matter complexation.
      Modelling of Ni geochemistry for test solutions other than those containing NOM
      showed consistent and minor differences between the WHAM and the BLM. The latter
      model was used to develop a comprehensive prediction model of Ni toxicity. logK
      values developed for competitive cationic effects showed that Ca and Mg have a
      much higher protective effect in soft water compared to models developed for
      Daphnia magna in hard water. The BLM developed for this species in soft water
      provided good predictions of toxicity across a wide range of Ni concentrations
      but also highlighted the need for an improved understanding of the effects of NOM
      and pH on Ni toxicity in soft waters.

PMID- 19111358
TI  - Creatinine and eGFR are similarly predictive of outcome of acute coronary
      syndrome.
AB  - INTRODUCTION: This study aimed to compare the ability of creatinine and estimated
      glomerular filtration rate (eGFR) to predict outcome in unselected patients with
      acute coronary syndrome (ACS). METHODS: Data on renal function at admission and
      in-hospital outcome were available for 781 of 1165 consecutive admissions with
      definite or suspected ACS to two Scottish district general hospitals. The c
      statistic was used to compare the ability of serum creatinine and eGFR to predict
      in-hospital death or major acute coronary event (MACE) defined as recurrent
      myocardial infarction, recurrent ischaemia requiring percutaneous intervention or
      death. RESULTS: There were no significant differences between the c-statistic for
      prediction of death (creatinine 0.76 (95% CI 0.68-0.84), eGFR 0.80 (95% CI 0.73
      0.87)) or MACE (creatinine 0.63 (95% CI 0.57-0.69), eGFR 0.61 (95% CI 0.55
      0.67)). CONCLUSION: Creatinine and eGFR are similarly predictive in stratifying
      risk of mortality and MACE in 'real world' patients with acute coronary syndrome.

PMID- 19111359
TI  - Magnetic resonance in isolated noncompaction of the ventricular myocardium.
AB  - Non-compaction of the ventricular myocardium (LCVM) is a rare disorder of
      myocardial morphogenesis usually diagnosed in paediatric age. The diagnosis was
      echocardiographically made on the basis of a reported spongeous/compacted ratio
      >2 in one or more segments of the left ventricle during the diastolic period. We
      aimed to test the diagnostic accuracy of cardiovascular magnetic resonance (CMR)
      imaging in distinguishing pathological left ventricular non-compaction. METHODS:
      We collected a consecutive series of 8 patients, 5 males and 3 females, with a
      mean age of 14.9 years with non-compaction of left ventricular myocardium. All
      patients were admitted in our divisions of cardiology. In all cases the diagnosis
      was performed by echocardiography. The diagnosis was obtained when the
      spongeous/compacted ratio was >2 in one or more segments of left ventricle,
      evaluated in systolic and diastolic period. In the end we completed the diagnosis
      by scanning with a Signa HD 1.5 T (GE, Milwaukee, USA) the same 8 patients
      affected by non compaction of ventricular myocardium. In all patients cardiac
      gated T1 and T2 black-blood FSE images in short axis and in four-chamber
      horizontal long axis were obtained. Breath hold cine MR sequences (FIESTA) were
      performed, covering the whole left ventricle in short-axis plane and in four
      chamber view. A segmented inversion-recovery fast gradient echo sequence (IR-FGE)
      was performed in the short-axis plane of the LV and in four-chamber-view after
      Gadolinium injection in 8 patients affected by non compaction of left ventricle.
      At the end of examination the spongeous/compacted ratio >2 was calculated in all
      involved segments of the left ventricle in diastole. RESULTS: In all cases we
      demonstrated by echocardiography an involvement of the ventricular apex. In 3
      cases the structural alterations involved also lateral wall of left ventricle.
      Magnetic resonance evaluation showed that involvement demonstrated by the
      echocardiogram was the same: ventricular apex involved in every patient, lateral
      wall in 3 and all segments in 2. However the spongeous/compacted ratio was >>2 in
      all patients, with a mean value of 3,1. CONCLUSIONS: Although our data refer to a
      small population of patients and need further confirmation, they suggest that it
      seems reasonable increase the cut-off for spongeous/compacted ratio from a value
      of 2 to 2.5 for non-compaction diagnosis when high-resolution magnetic resonance
      is used.

PMID- 19111360
TI  - Direct versus indirect standardization in risk adjustment.
AB  - Direct and indirect standardization procedures aim at comparing differences in
      health or in health care expenditures between subgroups of the population after
      controlling for observable morbidity differences. There is a close analogy
      between this problem and the issue of risk adjustment in health insurance.
      Traditional methods of risk adjustment are analogous to indirect standardization.
      They are equivalent to the so-called conditional egalitarian mechanism in social
      choice. In general, they do not remove incentives for risk selection, even if the
      effect of non-morbidity variables is correctly taken into account. A method of
      risk adjustment based on direct standardization does remove the incentives for
      risk selection, but at the cost of violating a neutrality condition, stating that
      insurers should receive the same premium subsidy for all members of the same risk
      group. Direct standardization is equivalent to the egalitarian-equivalent (or
      proportional) mechanism in social choice. The conflict between removing
      incentives for risk selection and neutrality is unavoidable if the health
      expenditure function is not additively separable in the morbidity and efficiency
      variables.

PMID- 19111361
TI  - Biogenic metals in advanced water treatment.
AB  - Microorganisms can change the oxidation state of metals and concomitantly deposit
      metal oxides and zerovalent metals on or into their cells. The microbial
      mechanisms involved in these processes have been extensively studied in natural
      environments, and researchers have recently gained interest in the applications
      of microbe-metal interactions in biotechnology. Because of their specific
      characteristics, such as high specific surface areas and high catalytic
      reactivity, biogenic metals offer promising perspectives for the sorption and
      (bio)degradation of contaminants. In this review, the precipitation of biogenic
      manganese and iron species and the microbial reduction of precious metals, such
      as palladium, platinum, silver and gold, are discussed with specific attention to
      the application of these biogenic metals in innovative remediation technologies
      in advanced water treatment.

PMID- 19111362
TI  - Dosimetric comparison of stereotactic body radiotherapy using 4D CT and
      multiphase CT images for treatment planning of lung cancer: evaluation of the
      impact on daily dose coverage.
AB  - PURPOSE: To investigate the dosimetric impact of using 4D CT and multiphase
      (helical) CT images for treatment planning target definition and the daily target
      coverage in hypofractionated stereotactic body radiotherapy (SBRT) of lung
      cancer. MATERIALS AND METHODS: For 10 consecutive patients treated with SBRT, a
      set of 4D CT images and three sets of multiphase helical CT scans, taken during
      free-breathing, end-inspiration and end-expiration breath-hold, were obtained.
      Three separate planning target volumes (PTVs) were created from these image sets.
      A PTV(4D) was created from the maximum intensity projection (MIP) reconstructed
      4D images by adding a 3mm margin to the internal target volume (ITV). A PTV(3CT)
      was created by generating ITV from gross target volumes (GTVs) contoured from the
      three multiphase images. Finally, a third conventional PTV (denoted PTV(conv))
      was created by adding 5mm in the axial direction and 10mm in the longitudinal
      direction to the GTV (in this work, GTV=CTV=clinical target volume) generated
      from free-breathing helical CT scans. Treatment planning was performed based on
      PTV(4D) (denoted as Plan-1), and the plan was adopted for PTV(3CT) and PTV(conv)
      to form Plan-2 and Plan-3, respectively, by superimposing "Plan-1" onto the
      helical free-breathing CT data set using modified beam apertures that conformed
      to either PTV(3CT) or PTV(conv). We first studied the impact of PTV design on
      treatment planning by evaluating the dosimetry of the three PTVs under the three
      plans, respectively. Then we examined the effect of the PTV designs on the daily
      target coverage by utilizing pre-treatment localization CT (CT-on-rails) images
      for daily GTV contouring and dose recalculation. The changes in the dose
      parameters of D(95) and D(99) (the dose received by 95% and 99% of the target
      volume, respectively), and the V(p) (the volume receiving the prescription dose)
      of the daily GTVs were compared under the three plans before and after setup
      error correction. RESULTS: For all 10 patients, we found that the PTV(4D)
      consistently resulted in the smallest volumes compared with the other PTV's
      (p=0.005). In general, the plans generated based PTV(3CT) could provide
      reasonably good coverage for PTV(4D), while the reverse can only achieve 90% of
      the planned values for PTV(3CT). The coverage of both PTV(4D) and PTV(3CT) in
      Plan-3 generally reserves the original planned values in terms of D(95), D(99),
      and V(p,) with the average ratios of 0.996, 0.977, and 0.977, respectively, for
      PTV(3CT), and 1.025, 1.025, and 1.0, respectively, for PTV(4D). However, it
      increased the dose significantly to normal lung tissue. Additionally, the plans
      generated using the PTV(4D) presented an equivalent daily target coverage
      compared to the plans generated using the PTV(3CT) (p=0.953) and PTV(conv)
      (p=0.773) after setup error correction. Consequently, this minimized the dose to
      the surrounding normal lung. CONCLUSION: Compared to the conventional approach
      using helical images for target definition, 4D CT and multiphase 3D CT have the
      advantage to provide patient-specific tumor motion information, based on which
      such designed PTVs could ensure daily target coverage. 4D CT-based treatment
      planning further reduces the amount of normal lung being irradiated while still
      providing a good target coverage when image guidance is used.

PMID- 19111363
TI  - Effects of NADPH oxidase inhibitor on diabetic nephropathy in OLETF rats: the
      role of reducing oxidative stress in its protective property.
AB  - Diabetic nephropathy is the most serious complication in diabetes mellitus.
      Oxidative stress via nicotinamide adenine dinucleotide phosphate (NADPH) oxidase
      and vascular endothelial growth factor (VEGF) pathway play critical roles in the
      development of diabetic nephropathy. We evaluated the effects of apocynin, NADPH
      oxidase inhibitor on diabetic nephropathy in a type 2 diabetic rat model. Sixteen
      Otsuka Long Evans Tokushima Fatty (OLETF) rats and 9 Long Evans Tokushima Otsuka
      (LETO) were divided into the following three groups: LETO rats (n=9), control
      OLETF rats (n=7) and apocynin-treated OLETF rats (n=9). We examined body weights,
      plasma glucose levels, urinary albumin-creatinine ratio (ACR) and protein
      creatinine ratio (PCR). At 50 weeks, experimental rats were sacrificed and their
      kidneys were extracted for hematoxylin eosin stain, immunohistochemical VEGF
      stain and VEGF mRNA real-time RT-PCR. To examine oxidative stress, we checked 24h
      urinary 8-OHdG (8-hydroxy-2'-deoxyguanosine) and MDA (malondialdehyde). Urinary
      protein and albumin excretions were reduced after apocynin treatment, though
      apocynin could not significantly decrease serum glucose levels. There were
      improvements of glomerular and mesangial expansion in the apocynin-treated OLETF
      rats. Apocynin significantly decreased optical density of glomerular VEGF
      expression in immunohistochemical stain and reduced the concentration of 24h
      urinary 8-OHdG and MDA. From these results, it was suggested that apocynin may
      have the potential to protect against diabetic nephropathy via amelioration of
      oxidative stress.

PMID- 19111364
TI  - Prevalence and correlates of undiagnosed depression among U.S. adults with
      diabetes: the Behavioral Risk Factor Surveillance System, 2006.
AB  - AIMS: Many people with depression may be undiagnosed and thus untreated. We
      sought to assess the prevalence and correlates of undiagnosed depression among
      adults with diabetes. METHODS: Data of U.S. adults from the Behavioral Risk
      Factor Surveillance System in 2006 were analyzed. Cox proportional hazard
      regression analysis was used to estimate prevalence ratios (PRs) and 95%
      confidence intervals (CIs) of correlates for undiagnosed depression. RESULTS: The
      unadjusted and age-adjusted prevalences of undiagnosed depression were 8.7% and
      9.2%. About 45% of diabetes patients with depression were undiagnosed. After
      adjustments for all correlates, female gender (PR, 1.4; 95% CI: 1.1-1.8), poor or
      fair health (PR, 2.8; 95% CI: 2.1-3.6), lack of social and emotional support (PR,
      2.5; 95% CI: 1.8-3.3), life dissatisfaction (PR, 3.5; 95% CI: 2.2-5.5), use of
      special equipment (PR, 1.4; 95% CI: 1.1-1.8), no leisure-time physical activity
      (PR, 1.5; 95% CI: 1.2-1.9), and comorbid cardiovascular disease (PR, 1.5; 95% CI:
      1.2-1.9) were associated with undiagnosed depression. CONCLUSIONS: Undiagnosed
      depression among people with diabetes was common. Because depression is
      associated with increased risk of diabetes-related complications, early detection
      of depression is needed in clinical settings.

PMID- 19111365
TI  - Growth inhibition in antimycin A treated-lung cancer Calu-6 cells via inducing a
      G1 phase arrest and apoptosis.
AB  - Antimycin A (AMA) inhibits mitochondrial electron transport between cytochrome b
      and c. We evaluated the effects of AMA on the growth of human lung cancer cell
      line, Calu-6. AMA inhibited the growth of Calu-6 cells. AMA induced a G1 phase
      arrest of the cell cycle in these cells at 72h. AMA increased a cyclin-dependent
      kinase inhibitor (CDKI), p27 and decreased CDK2, CDK4, and CDK6, as well as
      cyclin D1 and cyclin E in Calu-6 cells. AMA also induced apoptosis in Calu-6
      cells. The apoptotic process in AMA-treated Calu-6 cells was accompanied by the
      up-regulation of Bax, the loss of mitochondrial membrane potential (DeltaPsi(m)),
      and the activation of caspase-3 and -8. All of the tested caspase inhibitors,
      especially pan-caspase inhibitor (Z-VAD), markedly rescued Calu-6 cells from AMA
      induced Calu-6 cell death. Inhibitors of pan-caspase and caspase-8 also prevented
      the loss of mitochondrial membrane potential (DeltaPsi(m)). AMA decreased the
      intracellular ROS levels but increased the O(2)(*-) levels in Calu-6 cells. In
      conclusion, AMA as a mitochondrial electron transport inhibitor decreased the
      growth of lung cancer Calu-6 cell via inducing a G1 arrest of the cell cycle and
      apoptosis.

PMID- 19111366
TI  - Cost of hospital-associated infections in Massachusetts.
AB  - The Massachusetts Department of Public Health appointed an Expert Panel to assess
      the problem of health care-associated infections (HAI) in the state and make
      recommendations regarding mandatory reporting. At the Expert Panel's request, a
      cost-of-illness study was conducted using available data sources. In
      Massachusetts, the excess hospital costs attributed to HAIs were estimated at
      approximately $233 to $275 million in 2006.

PMID- 19111368
TI  - [Oral anticoagulants and atrial fibrillation].
AB  - INTRODUCTION: Oral anticoagulants (OA) are effective in the prevention of
      cerebrovascular events among patients with atrial fibrillation (AF). However,
      several studies showed OA to be widely underused in these patients. The purpose
      of this study was to assess the use of OA and associated factors with non-use of
      this treatment. METHODS: We conducted a retrospective study of 233patients
      affected by non valvular AF hospitalized in our institution between 2005 and
      2007. Patients were stratified in three groups for stroke's risk (high, moderate
      and low) according to the international antithrombotic therapy recommendations.
      RESULTS: The average age of our patients was 64+/-14 years, with 35% of subjects
      being older than 75years. Hypertension was the more frequently reported risk
      factor for stroke (61%), followed by diabetes mellitus (19%) and congestive heart
      failure (12%). Five percent of the patients reported a stroke or a systemic
      embolic event history. Of the 233patients studied, 48% were stratified to the
      high risk group, among them 75% were being treated with OA, 20% with Aspirin and
      5% were taking no medications. To explore possible reasons for not prescribing
      anticoagulation, we analysed 27patients at high risk who did not receive OA. We
      found a low benefit/risk ratio (37%), neuropsychological impairment in 5%, a past
      bleeding episode in 6% but almost 50% of those patients reported no risk factors
      for haemorrhage. CONCLUSION: In our retrospective study, among 25% high-risk
      patients with non valvular AF were not treated with OA and one half of the
      patients report none of the factors associated with perceived or actual risk
      factors for bleeding. These data confirmed OA underuse, despite guidelines that
      delineate higher-risk patient populations for whom anticoagulation is
      recommended.

PMID- 19111367
TI  - Estimating the annual burden of health care-associated infections in Finnish
      adult acute care hospitals.
AB  - BACKGROUND: We estimated the burden of health care-associated infections (HAIs)
      occurring in Finnish adult acute care hospitals using national hospitalization
      data and estimates of HAI based on a recent national prevalence survey. METHODS:
      A total of 7531 non-HAI patients and 703 HAI patients (8.5%) identified in the
      prevalence survey were included in the study. Using the patients' national
      identity numbers and the prevalence survey date, we obtained data on
      hospitalizations, including discharge diagnoses from the National Hospital
      Discharge Registry (NHDR), and the dates and causes of death from the National
      Population Information System. We converted the prevalence of HAI into incidence
      using the Rhame-Sudderth formula, assessed the 28-day case fatality of the HAI
      patients, and then extrapolated the annual estimates of HAI burden from the total
      number of hospitalizations in adult acute care hospitals in 2005 (n = 804,456).
      We also assessed the sensitivity of the NHDR diagnoses in identifying HAIs.
      RESULTS: The estimated incidence of HAIs was 5.7% (95% confidence interval = 5.0%
      to 6.5%), and the 28-day case fatality was 9.8%. Thus, >8500 hospitalizations per
      million population annually would result in at least 1 HAI and approximately 270
      HAI-associated deaths within 28 days. The sensitivity of the NHDR diagnoses was
      34% (range by infection type, 0% to 67%). CONCLUSION: Our disease burden
      estimates can be used in health care planning and resource allocation. The NHDR
      was not a reliable source for case finding of HAIs.

PMID- 19111369
TI  - Preparation and participation of undergraduate students to inform culturally
      sensitive research.
AB  - Most student work as research assistants occurs at the graduate level of nursing
      education, and little is known about the role of undergraduate students as
      research assistants (RAs) in major research projects. Based on our desire to
      study Mexican American (MA) cancer caregivers, we needed bilingual and bicultural
      RAs to serve as data collectors with women who spoke Spanish and possessed
      cultural beliefs that influenced their caregiving. Following successful
      recruitment, orientation, and mentoring based on Bandura's social learning theory
      [Bandura, A., 2001. Social learning theory: an agentic perspective. Annual Review
      of Psychology 52, 1-26] and accepted teaching-learning principles, RAs engaged in
      various behaviors that facilitated study outcomes. Faculty researchers, RAs, and
      study participants benefitted greatly from the undergraduate student involvement
      in this project. This article describes successful student inclusion approaches,
      ongoing faculty-RA interactions, and lessons learned from the research team
      experience. Guidelines discussed support the potential for making the
      undergraduate RA role a useful and unique learning experience.

PMID- 19111370
TI  - Supporting academic publication: evaluation of a writing course combined with
      writers' support group.
AB  - Publication rates are a vital measure of individual and institutional
      performance, yet many nurse academics publish rarely or not at all. Despite
      widespread acceptance of the need to increase academic publication rates and the
      pressure university faculty may experience to fulfil this obligation, little is
      known about the effectiveness of practical strategies to support academic
      writing. In this small cohort study (n=8) comprising nurses and other
      professionals involved in university education, a questionnaire survey was used
      to evaluate the effectiveness of a one-week "Writing for Publication" course
      combined with a monthly writers support group to increase publication rates. Two
      year pre and post submissions increased from 9 to 33 articles in peer-reviewed
      journals. Publications (in print) per person increased from a baseline of 0.5-1.2
      per year. Participants reported increased writing confidence and greater
      satisfaction with the publishing process. Peer support and receiving recognition
      and encouragement from line managers were also cited as incentives to publish.
      Writing for publication is a skill that can be learned. The evaluated model of a
      formal writing course, followed by informal monthly group support meetings, can
      effectively increase publication rates.

PMID- 19111372
TI  - Job satisfaction of nurse teachers: a literature review. Part I: Measurement,
      levels and components.
AB  - Job satisfaction among nurses is of concern throughout the world but the
      satisfaction of nurse teachers has received less attention and no review of
      global research on the topic has been published. A comprehensive literature
      review (1976-2007) was undertaken from an international perspective (n=26 papers
      and 4 doctoral abstracts) to examine the state of knowledge about nurse teachers'
      job satisfaction over time. Coverage over the last 30 years was selected to
      examine if the level and contributing factors to nurse teachers' job satisfaction
      have changed during a time which has seen considerable developments and
      reorganization of nurse education as well as the role of nurse teachers. The
      purpose of this Part I paper is to: (i) review the different measurements of job
      satisfaction, (ii) report the job satisfaction levels of nurse teachers and,
      (iii) identify the components of job satisfaction of nurse teachers. This paper
      provides the foundation for the Part II paper which reviews the literature
      regarding the effects and related factors of nurse teachers' job satisfaction.

PMID- 19111371
TI  - Students' expectations, concerns and comprehensions when writing theses as part
      of their nursing education.
AB  - This study investigates students' expectations and apprehensions before starting
      writing their Bachelor thesis and their experiences after completion. The
      questionnaire, which consisted of open questions, was given to 171 students at
      the beginning of the thesis course; of these, 107 replied; at the end of the
      course a total of 150 students answered and returned the questionnaire. The
      answers were analysed according to content analysis. Seven themes describing
      expectations and apprehensions; and four themes describing experience after
      completion of the thesis emerged. The results show that students' experiences can
      be divided into two different groups. One group saw the thesis project as being
      an important preparation for future professional activities, and one group,
      consisting of only a few students, described the production of a thesis as being
      a nightmare. Nevertheless, all the students considered that their experience of
      learning and the insights gained, together with the learning skills acquired
      through writing would be of great value in their coming professional life, and
      that they had become aware of alternative ways of thinking. All the students were
      proud of the work they had completed, and some saw it as a form of recognition or
      a "craftsman's diploma".

PMID- 19111373
TI  - New best estimates for radionuclide solid-liquid distribution coefficients in
      soils. Part 3: miscellany of radionuclides (Cd, Co, Ni, Zn, I, Se, Sb, Pu, Am,
      and others).
AB  - New best estimates for the solid-liquid distribution coefficient (K(d)) for a set
      of radionuclides are proposed, based on a selective data search and subsequent
      calculation of geometric means. The K(d) best estimates are calculated for soils
      grouped according to the texture and organic matter content. For a limited number
      of radionuclides this is extended to consider soil cofactors affecting soil
      radionuclide interaction, such as pH, organic matter content, and radionuclide
      chemical speciation. Correlations between main soil properties and radionuclide
      K(d) are examined to complete the information derived from the best estimates
      with a rough prediction of K(d) based on soil parameters. Although there are
      still gaps for many radionuclides, new data from recent studies improve the
      calculation of K(d) best estimates for a number of radionuclides, such as
      selenium, antimony, and iodine.

PMID- 19111374
TI  - Cu and Zn mobilization in soil columns percolated by different irrigation
      solutions.
AB  - We investigated the effects of different concentrations of nitrate and ammonium
      in irrigation water on the mobilization of Zn and Cu in repacked soil columns
      with a metal-polluted topsoil and unpolluted subsoils over two and a half years.
      Soil solution samples were collected by suction cups installed at vertical
      distances of a few centimeters and analyzed for dissolved organic carbon (DOC),
      Cu, and Zn (total and labile). During high N treatments the pH decreased and the
      presence of exchangeable cations resulted in Zn mobilization from the surface
      soil. The nitrogen input stimulated the biological activity, which affected both
      concentration and characteristics of DOC and consequently Cu speciation. Metal
      leaching through the boundary between the polluted topsoil and the unpolluted
      subsoils increased soil-bound and dissolved metals within the uppermost 2cm in
      the subsoils. Our study shows that agricultural activities involving nitrogen
      fertilization can have a strong influence on metal leaching and speciation.

PMID- 19111375
TI  - Modeling the exposure of children and adults via diet to chemicals in the
      environment with crop-specific models.
AB  - Exposure to chemicals via diet is a major uptake pathway for many compounds but
      is often estimated in a rather generic way. We use a new model framework (NMF)
      with crop-specific models to predict the dietary intake by 4-5-year-old children
      and 14-75-year-old women of three environmental compounds from their background
      concentrations in soil and air. Calculated daily intakes of benzo(a)pyrene and
      2,3,7,8-TCDD are in good agreement with measured results from diet studies. The
      major source of both compounds in human diet is deposition from air. Inhalation
      of air and ingestion of soil play a minor role. Children take up more than twice
      the amount than adults per kg bodyweight, due to higher consumption per kg
      bodyweight. Contrary, the methods for indirect human exposure suggested in the
      Technical Guidance Document (TGD) for chemical risk assessment in the EU lead to
      overprediction, due to unrealistic consumption data and a false root model.

PMID- 19111376
TI  - Increasing CPR duration prior to first defibrillation does not improve return of
      spontaneous circulation or survival in a swine model of prolonged ventricular
      fibrillation.

PMID- 19111377
TI  - Ischaemia modified albumin in the diagnosis of acute coronary syndromes.
AB  - The early diagnosis of acute coronary syndrome remains problematic, despite
      recent improvements. Traditionally, the diagnosis of acute cardiac ischaemia
      relies on the combination of chest pain, electrocardiographic changes and
      elevation of serum markers. Troponins are currently the "gold standard" test for
      the detection of myocardial necrosis, but they are unsuitable for early
      diagnosis, as nearly 50% of patients may present to the emergency department with
      non-diagnostic concentrations. Ischaemia modified albumin increases within
      minutes after the onset of ischaemia, remains elevated for 6 to 12h, and returns
      to normal within 24h. Thus, it may be a valuable aid for the clinician enabling
      early detection of ischaemia before the development of myocardial necrosis. Its
      high sensitivity comes at the expense of a lower specificity because its increase
      may be due to ischaemia of other tissues such as gastrointestinal tissues or
      skeletal muscles tissues. This paper has focuses on the cardiology aspect of this
      biomarker, underlying its potential value in the emergency department.

PMID- 19111378
TI  - The impact of therapeutic hypothermia on neurological function and quality of
      life after cardiac arrest.
AB  - AIMS: To assess the impact of therapeutic hypothermia on cognitive function and
      quality of life in comatose survivors of out of Hospital Cardiac arrest (OHCA).
      METHODS: We prospectively studied comatose survivors of OHCA consecutively
      admitted in a 4-year period. Therapeutic hypothermia was implemented in the last
      2-year period, intervention period (n=79), and this group was compared to
      patients admitted the 2 previous years, control period (n=77). We assessed
      Cerebral Performance Category (CPC), survival, Mini Mental State Examination
      (MMSE) and self-rated quality of life (SF-36) 6 months after OHCA in the subgroup
      with VF/VT as initial rhythm. RESULTS: CPC in patients alive at hospital
      discharge was significantly better in the intervention period with a CPC of 1-2
      in 97% vs. 71% in the control period, p=0.003, corresponding to an adjusted odds
      ratio of a favourable cerebral outcome of 17, p=0.01. No significant differences
      were found in long-term survival (57% vs. 56% alive at 30 months), MMSE, or SF
      36. Therapeutic hypothermia (hazard ratio: 0.15, p=0.007) and bystander CPR
      (hazard ratio 0.19, p=0.002) were significantly related to survival in the
      intervention period. CONCLUSION: CPC at discharge from hospital was significantly
      improved following implementation of therapeutic hypothermia in comatose patients
      resuscitated from OCHA with VF/VT. However, significant improvement in survival,
      cognitive status or quality of life could not be detected at long-term follow-up.

PMID- 19111379
TI  - Comments on the article "Teenage pregnancies: obstetric characteristics and
      outcome" by Gupta et al. [Eur. J. Obstet. Gynecol. Reprod. Biol. 2008; 137(2):165
      71].

PMID- 19111380
TI  - Isolation of a novel yeast strain Candida digboiensis TERI ASN6 capable of
      degrading petroleum hydrocarbons in acidic conditions.
AB  - A novel yeast species Candida digboiensis TERI ASN6 was isolated from soil
      samples contaminated with acidic oily sludge (pH 1-3) from the Digboi refinery
      (Northeast India). The strain TERI ASN6 could degrade 73% of the total petroleum
      hydrocarbons present in the medium at pH 3 in a week. This strain presents a
      dimorphic behaviour and showed mycelia morphology when grown under stressed
      conditions such as low pH and in a medium containing petroleum hydrocarbons. The
      C. digboiensis strain could efficiently degrade the aliphatic and aromatic
      fractions of the acidic oily sludge at pH 3 as confirmed by gas chromatography.
      During the growth of TERI ASN6 in dibenzothiophene (DBT), DBT-sulfone and
      biphenyl-2-ol were detected. An active cytochrome P450 system, implicated in
      hydrocarbon oxidation, was also detected in this yeast using degenerated primers
      based on its conserved regions. This yeast is a potential candidate for petroleum
      bioremediation treatment of hydrocarbon contaminated acidic soils. Its
      physiological behaviour allows the strain to work efficiently where other
      hydrocarbon-degrading bacteria may not survive.

PMID- 19111381
TI  - Editorial comment on: Medium-term anatomic and function results of laparoscopic
      sacrocolpopexy beyond the learning curve.

PMID- 19111382
TI  - Medium-term anatomic and functional results of laparoscopic sacrocolpopexy beyond
      the learning curve.
AB  - BACKGROUND: Limited prospective data on the anatomic and functional outcome after
      laparoscopic sacrocolpopexy (LSC) are available in the literature. OBJECTIVE: To
      describe the medium-term anatomic and functional outcome of LSC. DESIGN, SETTING,
      AND PARTICIPANTS: Prospective consecutive series of 132 women with vaginal vault
      prolapse undergoing LSC between 2001 and 2006, which was after our learning
      curve. Patients with urodynamically proven stress incontinence (SI) underwent a
      concomitant tension-free vaginal tape (TVT) procedure. INTERVENTION: Patients
      underwent LSC with a polypropylene implant. MEASUREMENTS: Principal outcome
      measures were anatomic cure (stage 1 or lower) assessed by the Pelvic Organ
      Prolapse Quantification (POPQ) system and subjective cure and impact on quality
      of life measured by a standardised interview and, since its introduction in 2004,
      by a prolapse-specific quality-of-life questionnaire (P-QOL). RESULTS AND
      LIMITATIONS: At a mean follow-up of 12.5 mo, the anatomic cure rate for the apex
      was 98%. Anatomic failures elsewhere were mainly at the posterior compartment
      (18%). Subjective prolapse cure rate was 91.7%, and no patients required
      reoperation for recurrent prolapse. Symptoms of preoperative SI, urge
      incontinence, or constipation were cured in 43%, 46%, and 42% of patients,
      respectively. The rate of de novo SI was 7.3%. De novo constipation developed in
      5% and de novo dyspareunia developed in 19%. Patients' quality of life improved
      significantly. Erosions occurred in 4.5%, all within 1 yr. A limitation of the
      study is that the quality-of-life assessment score became available halfway
      through the study, limiting the number of preoperative observations (n=36).
      CONCLUSIONS: We demonstrated that LSC results in good anatomic outcome and
      subjective cure of prolapse symptoms at medium term. The posterior compartment
      was most vulnerable for recurrence.

PMID- 19111384
TI  - Editorial comment on: Medium-term anatomic and functional results of laparoscopic
      sacrocolpopexy beyond the learning curve.

PMID- 19111385
TI  - Precursor isoform of prostate-specific antigen and human kallikrein 2: two new
      promising biomarkers for the unsolved challenge of early prostate cancer
      detection.

PMID- 19111386
TI  - Breast cancer metastasis suppressor 1 (BRMS1) suppresses metastasis and
      correlates with improved patient survival in non-small cell lung cancer.
AB  - Breast cancer metastasis suppressor 1 (BRMS1) is a metastasis suppressor gene in
      several solid tumors. The role of BRMS1 in non-small cell lung cancer (NSCLC) is
      not well established. To assess in vitro and in vivo metastatic behavior H1299
      NSCLC cells stably expressing BRMS1 or a vector control were created. BRMS1
      expression significantly decreases both migration and invasion of NSCLC cells in
      vitro. Importantly, in flank xenografts, BRMS1 suppresses the formation of
      pulmonary and hepatic metastases but does not significantly affect primary tumor
      growth. To evaluate whether BRMS1 is related to the progression of NSCLC, we
      examined BRMS1 expression in human NSCLC. Both BRMS1 mRNA and protein levels are
      diminished in NSCLC compared to adjacent non-cancerous lung. BRMS1 expression is
      also lower in squamous cell carcinoma compared to adenocarcinoma. Moreover,
      preservation of tumor BRMS1 expression is associated with improved patient
      survival. Thus, BRMS1 functions as a metastasis suppressor and may be a
      prognostic indicator for human NSCLC.

PMID- 19111387
TI  - Caspase-8 in cancer biology and therapy.
AB  - Caspase-8 belongs to the caspase family of proteases and plays a key role in the
      regulation of programmed cell death (apoptosis) during normal development as well
      as in adult life. Since signaling via the death receptor (extrinsic) pathway
      critically depends on caspase-8, the disturbance of caspase-8 expression or
      function may contribute to human diseases. For example, caspase-8 is inactivated
      in a variety of human cancers, which may promote tumor progression as well as
      resistance to current treatment approaches. Therefore, caspase-8 presents a
      promising target to restore defective apoptosis programs in cancers in order to
      overcome resistance.

PMID- 19111388
TI  - Increased topoisomerase IIalpha expression in colorectal cancer is associated
      with advanced disease and chemotherapeutic resistance via inhibition of
      apoptosis.
AB  - Topoisomerase IIalpha is a nuclear enzyme that regulates the tertiary structure
      of DNA. The influence of topoisomerase IIalpha gene (TOP2A) or protein
      alterations on disease progression and treatment response in colorectal cancer
      (CRC) is unknown. The study investigated the clinical relevance of topoisomerase
      IIalpha in CRC using in vivo and in vitro models. Differentially expressed genes
      in early and late-stage CRC were identified by array comparative genomic
      hybridization (CGH). Cellular location of gene amplifications was determined by
      fluorescence in situ hybridization (FISH). Topoisomerase IIalpha levels,
      proliferation index, and HER2 expression were examined in 228 colorectal tumors
      by immunohistochemistry. Overexpression of topoisomerase IIalpha in vitro was
      achieved by liposome-based transfection. Cell growth inhibition and apoptosis
      were quantified using the crystal violet assay and flow cytometry, respectively,
      in response to drug treatment. Amplification of TOP2A was identified in 3 (7.7%)
      tumors using array CGH and confirmed using FISH. At the protein level,
      topoisomerase IIalpha staining was observed in 157 (69%) tumors, and both
      staining and intensity levels were associated with an aggressive tumor phenotype
      (p values 0.04 and 0.005, respectively). Using logistic regression analysis,
      topoisomerase IIalpha remained significantly associated with advanced tumor stage
      when corrected for tumor proliferation (p=0.007) and differentiation (p=0.001).
      No association was identified between topoisomerase IIalpha and HER2. In vitro,
      overexpression of topoisomerase IIalpha was associated with resistance to
      irinotecan (p=0.001) and etoposide chemotherapy (p=0.03), an effect mediated by
      inhibition of apoptosis. Topoisomerase IIalpha overexpression is significantly
      associated with alterations in tumor behavior and response to drug treatment in
      CRC. Our results suggest that gene amplification may represent an important
      mechanism underlying these changes.

PMID- 19111389
TI  - The disease relevance of human hepatocellular xenograft models: molecular
      characterization and review of the literature.
AB  - In recent years a number of new therapeutics has been developed that were not
      general toxins and inhibitors of cell division like classical chemotherapeutics,
      but were designed to target a specific pathway. A prerequisite for this
      development was the comprehensive characterization of molecular alterations
      occurring in human hepatocellular carcinoma (HCC). However, while much knowledge
      of the molecular pathogenesis of human HCC has been gained, the model systems
      used to test the functional relevance of these alterations and applied for
      preclinical evaluation of drug candidates are still poorly characterized. In this
      paper, we reviewed the literature about several commonly used HCC cell lines and
      xenotransplantation models and present our own data on the molecular
      characterization of these. Results obtained demonstrate that it is important to
      have a sound knowledge of the specific molecular constitution of the experimental
      model and to carefully evaluate the functional status of the pathway of interest.
      For this reason, we make the gene expression profiles publicly available to help
      researchers making an informed decision about which model to use.

PMID- 19111391
TI  - Targeting tumor angiogenesis with histone deacetylase inhibitors.
AB  - Solid tumor malignancies including breast, lung and prostate carcinomas are
      considered to be angiogenesis dependent. Tumor angiogenesis is often mediated by
      hypoxia secondary to tumor growth or by increased oncogenic signaling. Both
      mechanisms result in increased hypoxia-inducible factor-1 alpha (HIF-1alpha)
      signaling and its transcriptional target vascular endothelial growth factor
      (VEGF). Critical to HIF-1alpha signaling are post translational modifications
      including acetylation mediated by histone acetyltransferases (HATS) and
      deacetylation by histone deacetylases (HDACs). More recently, HDACs were shown to
      be up-regulated in response to hypoxia mediating increased HIF-1alpha signaling.
      HDAC inhibitors represent a new class of anti-cancer therapeutics which show
      great promise at inhibiting angiogenesis in pre-clinical animal models and early
      phase clinical trials. This review will discuss the role of HIF-1alpha and VEGF
      influence on tumor angiogenesis and how HDACs play a critical role in HIF-1alpha
      transcriptional activity. Furthermore it will also be discussed how targeting
      HDACs via their inhibition create new avenues in treating solid malignancies by
      increasing the activity of established and novel therapeutic applications.

PMID- 19111390
TI  - Helicobacter pylori virulence factors in gastric carcinogenesis.
AB  - Helicobacter pylori infection is the most important risk factor in the
      development of non-cardia gastric adenocarcinoma; host genetic variability and
      dietary co-factors also modulate risk. Because most H. pylori infections do not
      cause cancer, H. pylori heterogeneity has been investigated to identify possible
      virulence factors. The strongest candidates are genes within the cag (cytotoxin
      associated antigen) pathogenicity island, including the gene encoding the CagA
      protein, as well as polymorphic variation in the VacA vacuolating exotoxin and
      the blood group antigen binding adhesin BabA. Improved understanding of the
      pathogenesis of H. pylori-associated gastric cancer may improve risk
      stratification for prevention and therapy.

PMID- 19111392
TI  - The spatial-temporal distribution of the atmospheric polluting agents during the
      period 2000-2005 in the Urban Area of Guadalajara, Jalisco, Mexico.
AB  - In the large cities, the disordered urban development, the industrial activities,
      and the transport, have caused elevated concentrations of polluting agents and
      possible risks to the health of the population. The metropolises located in
      valleys with little ventilation (such as the Urban Area of Guadalajara: UAG)
      present low dispersion of polluting agents can cause high risk of respiratory and
      cardiovascular diseases. The objective of this work was to describe the spatial
      temporal distribution of the atmospheric polluting agents: carbon monoxide (CO),
      nitrogen dioxide (NO(2)), sulfur dioxide (SO(2)), particles smaller than 10
      microns (microm) (PM(10)) and ozone (O(3)) in the UAG during the period 2000
      2005. A spatial-temporal distribution analysis was made by means of graphic
      interpolation (Kriging method) of the statistical parameters of CO, NO(2), SO(2),
      PM(10) and O(3) with the collected data from eight stations of atmospheric
      monitoring in the UAG. The results show that the distributions of the atmospheric
      polluting agents are variable during the analyzed years. The polluting agent with
      highest concentration is PM(10) (265.42 microg/m(3)), followed by O(3) (0.11
      ppm), NO(2) (0.11 ppm), CO (9.17 ppm) and SO(2) (0.05 ppm). The most affected
      zone is the southeast of the UAG. The results showed that an important percentage
      of days exceed the Mexican norms of air quality (93-199 days/year).

PMID- 19111393
TI  - Ceramsite obtained from water and wastewater sludge and its characteristics
      affected by Fe2O3, CaO, and MgO.
AB  - To solve the disposal problems of residual sludges, wastewater treatment sludge
      (WWTS) and drinking-water treatment sludge (DWTS) were tested as components for
      producing ceramsite. Fe(2)O(3), CaO, and MgO were the major basic oxides in WWTS
      and DWTS, so their effect on characteristics of ceramsite was also investigated
      to optimize the process. Results show that WWTS and DWTS can be utilized for
      producing ceramsite with optimal contents of Fe(2)O(3), CaO, and MgO ranging 5
      8%, 2.75-7%, and 1.6-4%, respectively. Ceramsite within the optimal Fe(2)O(3),
      CaO, and MgO contents ranges was characterized using thermal analysis, X-ray
      diffraction (XRD), morphological structures analyses, and compressive strength
      measurements. Higher strength ceramsite with more complex crystalline phases and
      fewer pores can be obtained at 6%<or=Fe(2)O(3)<or=8%. Lower strength ceramsite
      with more pores and amorphous phases can be obtained at 5%<or=CaO<or=7%, which
      implies that excessive Ca(2+) exceeds the needed ions for producing electrical
      neutrality of silicate networks. Ceramsite characteristics are not dramatically
      influenced by MgO because Mg(2+) cannot destroy the unity of crystalline
      structures. This revolutionary technology of utilization of WWTS and DWTS can
      produce high performance ceramsite thus reducing costs of sludge disposal, in
      accordance with the concept of sustainable development.

PMID- 19111394
TI  - Evaluation of a TiO2 photocatalysis treatment on nitrophenols and nitramines
      contaminated plant wastewaters by solid-phase extraction coupled with ESI HPLC
      MS.
AB  - Nitration reactions of aromatic compounds are commonly involved in different
      industrial processes for pharmaceutical, pesticide or military uses. For many
      years, most of the manufacturing sites used lagooning systems to treat their
      process effluents. In view of a photocatalytic degradation assay, the wastewater
      of a lagoon was investigated by using HPLC coupled with mass spectrometry. The
      wastewater was highly concentrated in RDX (hexahydro-1,3,5-trinitro-1,3,5
      triazine), HMX (octahydro-1,3,5,7-tetranitro-1,3,5,7-tetrazocine) and two
      herbicides Dinoterb (2-tert-butyl-4,6-dinitrophenol) and Dinoseb (2-sec-butyl-4,6
      dinitrophenol). First of all, an analytical method using solid-phase extraction
      (SPE) combined with HPLC ESI MS/MS was put in work for identification and
      titration of RDX, HMX and the two dinitrophenols in a complex natural matrix.
      Then, the UV/TiO2 treatment was investigated for pollutants removal.
      Dinitrophenolic compounds were significantly degraded after a 8-h-exposition of
      the wastewater/TiO2 suspension, whereas RDX and HMX were poorly affected.

PMID- 19111395
TI  - Application of fly ash on the growth performance and translocation of toxic heavy
      metals within Cajanus cajan L.: implication for safe utilization of fly ash for
      agricultural production.
AB  - The present study was undertaken to examine the influence of the application of
      fly ash (FA) into garden soil for Cajanus cajan L. cultivation and on
      accumulation and translocation of hazardous metals from FA to edible part.
      Numerous studies have been reported on the growth and yield of agricultural crops
      under FA stress; however, there is a dearth of studies recommending the safe
      utilization of fly ash for crop production. Pot experiments were conducted on C.
      cajan L., a widely cultivating legume in India for its highly nutritious seeds.
      C. cajan L. were grown in garden soil and amended with varying concentrations of
      FA in a weight/weight ratio (0%, 25%, 50% and 100%; w/w). Incorporation of fly
      ash from 25% to 100% in garden soil increases the levels of pH, particle density,
      porosity and water holding capacity from 3.47% to 26.39%, 3.98% to 26.14%, 37.50%
      to 147.92% and 163.16% to 318.42%, respectively, than the control while bulk
      density decrease respectively from 8.94% to 48.89%. Pot experiment found that
      accumulation and translocation of heavy metals in tested plant depends on the
      concentration of FA. Addition of FA at lower concentration (25%) had shown
      positive results in most of the studied parameters of growth and yield (14.23%
      than control). The experimental results confirmed that lower concentration of FA
      (25%) is safe for C. cajan cultivation, which not only enhanced the yield of C.
      cajan L. significantly but also ensured the translocation of heavy metals to
      edible parts within the critical limits.

PMID- 19111396
TI  - Emissions investigation for a novel medical waste incinerator.
AB  - Medical waste constitutes one of the waste streams that should be dealt with
      special priority due to its potential negative impact on public health and on the
      environment. Incineration is a process that is widely used for the treatment of
      medical waste. However, self-supporting combustion of medical waste cannot avoid
      releasing many hazardous pollutants into our environment. The most favored
      solutions are firing additional fuels of high calorific value and direct
      purification by air pollution control devices (APCD). This process entails not
      only large first time investment but also an increase in the operation cost. A
      novel incinerator is proposed for better utilization of energy of the
      incineration process. Its originality is essentially due to combining a feeder, a
      rotary grate, a cylindrical gasifier and a "coaxial" secondary combustion chamber
      into a unique unit. The structure of the incinerator as well as the principle of
      the incineration process is presented in this paper. A full-scale trial of the
      novel incinerator with APCD was carried out from March to May 2008 to investigate
      how the distinct configuration influenced the incineration process. Data on PM,
      CO, NO(X), O(2) were recorded by a continuous emission monitoring system during
      the study period. Heavy metals and PCCD/Fs were also sampled and measured.
      Measuring results were compared with the China and U.S. EPA guidelines. The
      concentrations of contaminants were below their respective limits in emission
      control standards. Results from testing the novel medical waste incinerator
      confirmed that this technology has a good suitability for neutralization of
      medical wastes and purification of flue gases.

PMID- 19111397
TI  - Ammonia removal from air stream and biogas by a H2SO4 impregnated adsorbent
      originating from waste wood-shavings and biosolids.
AB  - A new and cost-effective adsorbent N-TRAP, made from waste wood-shavings and
      anaerobically digestion biosolids and impregnated with H(2)SO(4), was applied for
      the ammonia removal from air stream and biogas with high efficiency and
      effectiveness. Bearing a 75-80 and 65 wt.% sulfuric acid, the N-TRAPs mediated
      with wood shavings and biosolids showed the maximum ammonia adsorption capacity
      of 260-280 and 230 mg g(-1), respectively. Gas temperatures (20 and 60 degrees C)
      and moisture content (100% relative humidity) had no significantly negative
      effect on ammonia capture performance when temperature in the fixed-bed column
      was kept equalled to or slightly above the feed gas temperature. The pressure
      drop increased significantly when NH(3) began to break through the N-TRAP
      stripper due to the formation of ammonium sulfate blocking the vacuum space of
      packed adsorbent. At last, an alternative N-TRAP filter bed design was proposed
      to resolve the problem of pressure drop evolution.

PMID- 19111398
TI  - High- and low-frequency noise in Cs and in liquid metal ion sources.
AB  - Fundamental Physics space missions set rigid thrust noise limits for liquid metal
      ion thrusters used as actuators on drag-free platforms aboard the spacecraft. We
      have measured current-, voltage- and thrust noise of Cs and In LMIS, foreseen as
      prime candidates in these missions. In the high-frequency range, quasiperiodic
      oscillations around approximately 10(5)Hz can be observed for both types of
      emitters with frequency depending on emission current. In the low-frequency range
      (1-10(-3)Hz), which is particularly important for drag-free control, different
      types of noise events are observed, which in some instances show definite signs
      of deterministic chaos (period doubling, self-similarity). High-frequency current
      oscillations are generally ascribed to electro-hydrodynamic oscillations of the
      TAYLOR cone and the jet at its apex, with concomitant emission of charged
      nanodroplets. Comparison of theory and experiment shows unsatisfactory agreement
      in predicted vs. measured current oscillation frequencies and large disagreement
      in droplet emission frequencies. No theory is presently available for describing
      low-frequency noise events. In terms of a linearized Mair theory it is, however,
      shown that these noise events can be efficiently described by spontaneous
      variations in electrical emitter impedance. In spite of this impedance noise, the
      mission requirements for thrust noise (<0.1microN/Hz(1/2)) can be met by a thrust
      stabilized In emitter.

PMID- 19111399
TI  - Core outcomes for adult burn survivors: a clinical overview.
AB  - Burn trauma ranges from the minor burn to the devastating injury, which can
      impact on all aspects of a person's life including aesthetic appearance,
      relationships with others and psychological, social and physical functioning.
      Measurement of outcome in burns patients is therefore complex and multi-faceted.
      The increasing numbers of major burn survivors implies that understanding health
      outcomes in these patients has assumed high priority. This paper sets out a
      conceptual framework for unifying outcome measurement, which may be useful to all
      members of the multidisciplinary team who are contemplating outcome assessment in
      their burn patients. It outlines seven core domains of assessment which are (i)
      skin; (ii) neuromuscular function; (iii) sensory and pain; (iv) psychological
      function; (v) physical role function; (vi) community participation; and (vii)
      perceived quality of life. Within each domain, we present a brief clinical review
      of the most commonly administered measurement tools that have been, or
      potentially could be, used to assess aspects of these core domains. Where
      possible, the psychometric properties and clinical utility of these tools are
      presented. A concise discussion of key methodological issues which should be
      addressed in this assessment process is then provided, together with suggestions
      for future research.

PMID- 19111400
TI  - Intensity-modulated radiotherapy reduces radiation-induced morbidity and improves
      health-related quality of life: results of a nonrandomized prospective study
      using a standardized follow-up program.
AB  - PURPOSE: The purpose of this study was to compare intensity-modulated radiation
      therapy (IMRT) and three-dimensional conventional radiotherapy (3D-CRT) with
      regard to patient-rated xerostomia, Radiation Therapy Oncology Group (RTOG) acute
      and late xerostomia and health-related quality of life (HRQoL) among patients
      with head and neck squamous cell carcinoma (HNSCC). METHODS AND MATERIALS:
      Included were 241 patients with HNSCC treated with bilateral irradiation +/-
      chemotherapy. Since 2000, all patients treated with HNSCC were included in a
      program, which prospectively assessed acute and late morbidity according to the
      RTOG and HRQoL on a routine basis at regular intervals. Before October 2004, all
      patients were treated with 3D-CRT (N = 150). After clinical implementation in
      October 2004, 91 patients received IMRT. In this study, the differences regarding
      RTOG toxicity, xerostomia, and other items of HRQoL were analyzed. RESULTS: The
      use of IMRT resulted in a significant reduction of the mean dose of the parotid
      glands (27 Gy vs. 43 Gy (p < 0.001). During radiation, Grade 2 RTOG xerostomia
      was significantly less with IMRT than with 3D-CRT. At 6 months, the prevalence of
      patient-rated moderate to severe xerostomia and Grade 2 or higher RTOG xerostomia
      was significantly lower after IMRT versus 3D-CRT. Treatment with IMRT also had a
      positive effect on several general and head and neck cancer-specific HRQoL
      dimensions. CONCLUSIONS: IMRT results in a significant reduction of patient- and
      observer-rated xerostomia, as well as other head and neck symptoms, compared with
      standard 3D-CRT. These differences translate into a significant improvement of
      the more general dimensions of HRQoL.

PMID- 19111401
TI  - The role of seminal vesicle motion in target margin assessment for online image
      guided radiotherapy for prostate cancer.
AB  - PURPOSE: For patients with intermediate- and high-risk prostate cancer, the
      seminal vesicles (SVs) are included in the clinical target volume (CTV). The
      purposes of this study are to investigate interfraction motion characteristics of
      the SVs and determine proper margins for online computed tomography image
      guidance. METHODS AND MATERIALS: Twenty-four patients, each with 16 daily helical
      computed tomography scans, were included in this study. A binary image mask was
      used for image registration to determine daily organ motion. Two online image
      guided radiotherapy strategies (prostate only and prostate + SVs) were simulated
      in a hypofractionated scheme. Three margin designs were studied for both three
      dimensional conformal radiotherapy and intensity-modulated radiotherapy (IMRT).
      In prostate-only guidance, Margin A was uniformly applied to the whole CTV, and
      Margin B was applied to the SVs with a fixed 3-mm prostate margin. In prostate
      plus SV guidance, Margin C was uniformly applied to the CTV. The minimum margins
      were sought to satisfy the criterion that minimum cumulative CTV dose be more
      than those of the planning target volume in the plan for greater than 95% of
      patients. RESULTS: The prostate and SVs move significantly more in the anterior
      posterior and superior-inferior than right-left directions. The anterior
      posterior motion of the prostate and SVs correlated (R(2) = 0.7). The SVs move
      significantly more than the prostate. The minimum margins found were 2.5 mm for
      three-dimensional conformal radiotherapy and 4.5, 4.5, and 3.0 mm for Margins A,
      B, and C for IMRT, respectively. Margins for IMRT were larger, but the irradiated
      volume and doses to critical structures were smaller. Minimum margins of 4.5 mm
      to the SVs and 3 mm to the prostate are recommended for IMRT with prostate-only
      guidance. CONCLUSIONS: The SVs move independently from the prostate gland, and
      additional margins are necessary for image-guided radiotherapy.

PMID- 19111402
TI  - Predictive factors for acute and late urinary toxicity after permanent prostate
      brachytherapy: long-term outcome in 712 consecutive patients.
AB  - PURPOSE: To describe the frequency of acute and late Radiation Therapy Oncology
      Group (RTOG) urinary toxicity, associated predictive factors, and resolution of
      International Prostate Symptom Score (IPSS) in 712 consecutive prostate
      brachytherapy patients. METHODS AND MATERIALS: Patients underwent implantation
      between 1998 and 2003 (median follow-up, 57 months). The IPSS and RTOG toxicity
      data were prospectively collected. The patient, treatment, and implant factors
      were examined for an association with urinary toxicity. The time to IPSS
      resolution was examined using Kaplan-Meier curves, and multivariate modeling of
      IPSS resolution was done using Cox proportional hazards regression analysis.
      Logistic regression analysis was used to examine the factors associated with
      urinary toxicity. RESULTS: The IPSS returned to baseline at a median of 12.6
      months. On multivariate analysis, patients with a high baseline IPSS had a
      quicker resolution of their IPSS. Higher prostate D90 (dose covering 90% of the
      prostate), maximal postimplant IPSS, and urinary retention slowed the IPSS
      resolution time. The rate of the actuarial 5-year late urinary (>12 months) RTOG
      Grade 0, 1, 2, 3, and 4 was 32%, 36%, 24%, 6.2%, and 0.1%, respectively. At 7
      years, the prevalence of RTOG Grade 0-1 was 92.5%. Patients with a larger
      prostate volume, greater number of needles, greater baseline IPSS, and use of
      hormonal therapy had more acute toxicity. On multivariate analysis, the
      significant predictors for late greater than or equal to RTOG toxicity 2 were a
      greater baseline IPSS, maximal postimplant IPSS, presence of acute toxicity, and
      higher prostate V150 (volume of the prostate covered by 150% of the dose). More
      recently implanted patients had less acute urinary toxicity and patients given
      hormonal therapy had less late urinary toxicity (all p < 0.02). CONCLUSION: Most
      urinary symptoms resolved within 12 months after prostate brachytherapy, and
      significant long-term urinary toxicity was very low. Refined patient selection
      and greater technical experience in prostate brachytherapy were associated with
      less urinary toxicity.

PMID- 19111403
TI  - The serotonin 2A receptor gene in alcohol dependence and tobacco smoking.
AB  - Alcohol and nicotine abuse and dependence are multifactorial traits that
      frequently co-occur, where 80-90% of alcohol-dependent individuals who seek
      treatment smoke. Nicotine is the main compound of tobacco and one of its effects
      is to increase the release of serotonin. Variations in the serotonergic system
      may influence some aspects of smoking. The serotonin receptor gene HTR2A has been
      a candidate gene with some evidence for association with alcohol and nicotine
      dependencies. The polymorphism HTR2A A-1438G is a functional SNP, and the
      presence of the A allele increases the transcriptional activity of the gene. The
      aim of the present study was to test for possible associations between the A
      1438G polymorphism in the serotonin receptor gene (HTR2A) with tobacco smoking
      combined or not with alcohol dependence. The polymorphic site was genotyped in
      three groups of European-derived Brazilians: individuals with co-occurrence of
      alcohol dependence and tobacco smoking (n=113), non-alcoholic smokers (n=120) and
      non-smoking controls (n=115). A higher frequency of the A allele was observed in
      the two groups of smokers than in the non-smoking controls (chi(2)=6.53, p=0.04).
      Combining these groups in comparison with the control group, the difference is
      more significant (chi(2)=6.45, p=0.01). These results support previous evidence
      for association between HTR2A polymorphisms and substance use disorders.

PMID- 19111405
TI  - Different replication characteristics of historical pseudorabies virus strains in
      porcine respiratory nasal mucosa explants.
AB  - Different alphaherpesviruses, including pseudorabies virus (PRV), are able to
      cross the basement membrane barrier in nasal respiratory epithelium. As a first
      step in investigating this invasion process, a detailed quantitative analysis
      system was set up to determine the kinetics of horizontal and vertical virus
      spread in nasal explants, using the virulent PRV strain 89V87. Plaque latitudes,
      total depths, depths measured from the basement membrane and volumes were
      determined at 0, 12, 24 and 36h post inoculation (pi). PRV 89V87 was found to
      spread in a plaquewise manner and to cross the basement membrane between 12 and
      24hpi. During the 1960s-1970s, an increase in PRV virulence has been reported. To
      analyse potential differences in efficiency of infection and spread for different
      historical PRV strains, single infected cells and plaques of infected cells were
      quantified at 12 and 36hpi in nasal mucosa explants for seven European PRV
      strains, isolated in the 1960s (Becker, NIA1), the 1970s (NS374, NIA3, 75V19) and
      later (89V87, 00V72). All viruses were used at second passage in cell culture,
      except for the Becker strain, which had an unknown passage history. Older
      strains, Becker, NIA1 and/or NS374, showed lower numbers of primary infectious
      centers, lower capacity to form plaques and/or lower capacity to cross the
      basement membrane. The observed differences in virus-mucosa interactions may aid
      in understanding the virulence increase of PRV. The quantitative assay
      established here will be of use in unravelling the mechanism of alphaherpesvirus
      mediated invasion through the basement membrane.

PMID- 19111404
TI  - Associations of glutamate decarboxylase genes with initial sensitivity and age-at
      onset of alcohol dependence in the Irish Affected Sib Pair Study of Alcohol
      Dependence.
AB  - BACKGROUND: The relation of gamma-aminobutyric acid (GABA) to alcohol dependence
      (AD) has been widely studied. Several previous studies suggest that GABA may be
      involved in alcohol withdrawal, tolerance, and the symptoms that form an AD
      diagnosis. The genes coding for glutamate decarboxylase (GAD), the rate-limiting
      enzyme in GABA synthesis, are of potential interest for their association to
      ethanol consumption and AD. There are two isoforms of GAD, GAD1 and GAD2, which
      were reported to be associated with AD in males of Han Taiwanese (GAD1) and
      Russian (GAD2) ancestry. The present study examined the association of the two
      GAD isoforms with AD and relevant alcohol-related traits in the Irish Affected
      Sib Pair Study of Alcohol Dependence [Prescott, C.A., Sullivan, P.F., Myers,
      J.M., Patterson, D.G., Devitt, M., Halberstadt, L.J., Walsh, D., Kendler, K.S.,
      2005. The Irish Affected Sib Pair Study of Alcohol Dependence: study methodology
      and validation of diagnosis by interview and family history. Alcohol.-Clin. Exp.
      Res. 29 (3) 417-429]. METHODS: Participants were recruited in Ireland, including
      575 independent cases who met DSM-IV AD criteria and 530 controls, screened for
      heavy drinking. We first conducted case-control analyses of the GAD genes with AD
      and, within the cases, examined associations with age at onset of AD, withdrawal
      symptoms, and two quantitative measures: initial sensitivity and tolerance (based
      on scales from the Self-Rating of the Effects of Ethanol) [Schuckit, M.A., Smith,
      T.L., Tipp, J.E., 1997. The self-rating of the effects of alcohol (SRE) form as a
      retrospective measure of the risk for alcoholism. Addiction 92, 979-988]. A total
      of 29 SNPs were genotyped for GAD1 and GAD2 using the Illumina GoldenGate
      protocols. Statistical procedures were implemented to control for false discovery
      rates (FDR). RESULTS: Nine of 29 markers with minor allele frequencies less than
      0.01 were removed from standard analysis; the remaining 20 markers were all in
      Hardy-Weinberg equilibrium. Three markers in the intronic regions of GAD1 were
      associated with initial sensitivity to alcohol (P=0.002); the associations
      remained significant after a FDR based correction for multiple testing. In
      addition, one marker located 3kb upstream of GAD1 exhibited association with age
      at onset of AD (P=0.0001). Gender specific effects were observed in results of
      both single marker and haplotype analyses. CONCLUSION: We found no evidence for
      the association of GAD genes with AD but significant association of GAD1 with
      initial sensitivity and age at onset of AD. Our findings suggest that the
      underlying pathophysiology regulated by genes like GAD1 may be more directly
      related to the component processes that form AD than to the clinical disorder.

PMID- 19111406
TI  - Isolation of Streptococcus suis from a cat with meningoencephalitis.

PMID- 19111407
TI  - Successful cryopreservation of Asian elephant (Elephas maximus) spermatozoa.
AB  - Reproduction in captive elephants is low and infant mortality is high,
      collectively leading to possible population extinction. Artificial insemination
      was developed a decade ago; however, it relies on fresh-chilled semen from just a
      handful of bulls with inconsistent sperm quality. Artificial insemination with
      frozen-thawed sperm has never been described, probably, in part, due to low semen
      quality after cryopreservation. The present study was designed with the aim of
      finding a reliable semen freezing protocol. Screening tests included freezing
      semen with varying concentrations of ethylene glycol, propylene glycol,
      trehalose, dimethyl sulfoxide and glycerol as cryoprotectants and assessing
      cushioned centrifugation, rapid chilling to suprazero temperatures, freezing
      extender osmolarity, egg yolk concentration, post-thaw dilution with
      cryoprotectant-free BC solution and the addition of 10% (v/v) of autologous
      seminal plasma. The resulting optimal freezing protocol uses cushioned
      centrifugation, two-step dilution with isothermal 285 m Osm/kg Berliner
      Cryomedium (BC) with final glycerol concentration of 7% and 16% egg yolk, and
      freezing in large volume by the directional freezing technique. After thawing,
      samples are diluted 1:1 with BC solution. Using this protocol, post-thaw
      evaluations results were: motility upon thawing: 57.2+/-5.4%, motility following
      30 min incubation at 37 degrees C: 58.5+/-6.0% and following 3h incubation:
      21.7+/-7.6%, intact acrosome: 57.1+/-5.2%, normal morphology: 52.0+/-5.8% and
      viability: 67.3+/-6.1%. With this protocol, good quality semen can be accumulated
      for future use in artificial inseminations when and where needed.

PMID- 19111410
TI  - The fatal injuries of car drivers.
AB  - We often refer to road fatalities without knowing exactly what injuries are
      responsible for them. Based on the Rhone Road Trauma Registry this paper sets out
      to describe the topography, nature and frequency of the fatal injuries sustained
      by car drivers. Mean annual mortality at the wheel of a car, computed by dividing
      the total number of drivers killed (n=383) by the population of the Rhone
      Departement (1.6 million) during the period 1996-2004 was 5.41 males per 100,000
      and 1.41 females per 100,000, with 78% of the casualties residing in the
      Departement. A reduction has been observed since 2003. Three-quarters of the
      casualties died at the scene of the crash. The results confirm the effectiveness
      of seat belts. The observed lethality was 0.43% for unbelted drivers and 2.7% for
      belted drivers (RR=0.16 [0.12; 0.21]). The injuries were analyzed for the 287
      killed drivers whose deaths could be explained by the described injuries (at
      least one AIS 4+ injury). Of these, 41% had an ISS of 75 (at least one AIS 6
      injury), 21% had an ISS of between 40 and 74, 33% an ISS of between 25 and 40,
      and 6% an ISS of between 16 and 24. In the case of all the AIS 4+ injuries, the
      three most frequent locations for injuries were the thorax only (30% of
      casualties), the head only (23%) and a combination of the two (18%). Abdominal
      injuries occurred in only 10% of casualties and spinal injuries in 9% of
      casualties. In the thorax, the most common injury was flail chest with
      haemothorax or pneumothorax. In the case of the head, the most frequent injuries
      were to the brain (haemorrhage, haematoma and axonal injuries). Complex fractures
      of the base of the skull were the second most common craniocephalic injuries. In
      spite of the use of restraint devices, the thorax and head are still the priority
      vital areas for protection in the case of car drivers. For one in four of the
      fatalities, death cannot be explained by any of the injuries we know about. As
      road traffic accidents are considered to be a cause of death in their own right,
      autopsies are rarely performed in France on such fatalities. This means we do not
      know about any injuries that cannot be detected by an external examination of the
      cadaver.

PMID- 19111409
TI  - Estrogen effects on pilocarpine-induced temporal lobe epilepsy in rats.
AB  - OBJECTIVE: To evaluate the effects of conjugated equine estrogens (CEE) on the
      pilocarpine-induced epilepsy in rats. STUDY DESIGN: 40 female rats were divided
      into: GPC (positive control) presented "status epilepticus" (SE) induced by
      pilocarpine; GOC (ovariectomized control) only castrated; GNC (negative control)
      received only saline solution; GPE received pilocarpine, presented SE, castrated
      and received 50microg/kg CEE treatment; GPV received pilocarpine, castrated and
      received propylene glycol (vehicle). The animals were monitored by a video
      system. At the end of observation, the brains removed for later histologic
      analysis using Neo-Timm and Nissl methods. RESULTS: The GPE presented a reduction
      in number of seizures compared to GPV. The Neo-Timm analysis showed that GPV had
      greater sprouting of mossy fibers, with a denser band in the area of the dentate
      gyrus hilum compared to GPE. On Nissl staining, GPE showed evident neuronal loss
      in the CA3 area. GPV presented loss in CA1 and dentate gyrus. CONCLUSION:
      Estrogen may have a protecting effect on the central nervous system.

PMID- 19111411
TI  - Complex suicide versus complicated suicide.
AB  - In complex suicides, two or more methods are applied either simultaneously or one
      after the other. The purpose of the present study was to distinguish such complex
      suicides in the proper sense from "complicated suicides", which are characterized
      by an unintentional secondary traumatization following the original suicide
      method. The study material comprises 1217 suicides investigated at the Budapest
      Institute of Forensic Medicine in the period from 2004 to 2006. Among these,
      4.43% (n=54) accounted for planned or unplanned complex suicides, whereas 0.49%
      (n=6) were categorized as "complicated suicides". The latter group included four
      fatalities due to unintended falls from a height (for instance after breaking of
      the hanging noose), one death from electrocution and one case of drowning. The
      succession of a failed suicidal act and a secondary ("unforeseen" and therefore
      "accidental") trauma with fatal outcome may cause problems in determining the
      manner and cause of death.

PMID- 19111412
TI  - Risk factors of postoperative infection in head and neck surgery.
AB  - OBJECTIVES: Patients undergoing head and neck oncological surgery are at great
      risk of developing complications following surgery. It is important to clarify
      risk factors contributing to operative wound infections. METHODS: Two hundred and
      nine cases with head and neck tumor (87 female, and 122 male, averaged 58.6 years
      old) were studied at Mie University Hospital within a 24-month interval, during
      2002 and 2003. RESULTS: Twenty-one (10.0%) surgical site infections (SSIs) were
      recorded. Univariate analysis revealed that the following factors were
      significantly related to SSI: blood loss, previous chemotherapy, clean
      contaminated surgery, tracheotomy, malignant tumor, advanced T-stage, flap
      reconstruction, and long operative time. Multivariate analysis showed that blood
      loss, previous chemotherapy, and the type of surgery contributed to SSI.
      Otherwise, the following factors did not show any significant correlations: age,
      body mass index, smoking, alcohol intake, diabetes, sex, previous radiotherapy, N
      stage or ASA score. CONCLUSIONS: In order to minimize postoperative wound
      infection, clinicians managing the head and neck tumor patients should have a
      thorough understanding of the risk factors leading to postoperative infections
      such as blood loss, previous chemotherapy, and clean-contaminated surgery.

PMID- 19111408
TI  - Association of estrogen receptor 2 gene polymorphisms with obesity in women
      (obesity and estrogen receptor 2 gene).
AB  - OBJECTIVE: Few studies have examined the association between genetic variants of
      the estrogen receptor beta (ESR2) and obesity in postmenopausal women. METHODS:
      The relationship of three polymorphisms (rs1271572, rs1256049 and rs4986938) and
      their associated haplotypes in the ESR2 gene with obesity and overweight were
      evaluated in 561 apparently healthy women (median age 63 years) from the Women's
      Health Study. Most of the women were postmenopausal (99.1%). The associations
      between genotypes and haplotypes with obesity (BMI> or =30kg/m(2)) and overweight
      (BMI> or =25kg/m(2)) were evaluated by logistic regression, assuming an additive
      model. RESULTS: No association was observed for any of the three polymorphisms
      with BMI, overweight or obesity. In haplotype analyses, one haplotype (major
      allele for all polymorphisms) was associated with a borderline inverse
      association with overweight but not obesity (OR=0.62, 95% CI=0.39-0.98).
      CONCLUSIONS: An inverse and borderline significant association was found between
      the ESR2 G-G-G haplotype and overweight in postmenopausal women. Further
      investigation regarding the association between ESR2 and adiposity should be
      performed to confirm these findings.

PMID- 19111413
TI  - Ultrasonography for preoperative localization of enlarged parathyroid glands in
      secondary hyperparathyroidism.
AB  - OBJECTIVE: Parathyroidectomy (PTx) is sometimes performed to treat secondary
      hyperparathyroidism (2HPT) related to long-term dialysis. In this procedure, all
      four parathyroid glands should be resected. However, in patients with 2HPT, the
      four glands are not uniformly enlarged; therefore, preoperative diagnosis is
      difficult in comparison with primary hyperparathyroidism. We compared glands
      detected on preoperative ultrasonography (US) with those resected during PTx to
      examine the usefulness and limitations of US. METHODS: The subjects were 44
      patients with 2HPT who underwent PTx between December 2003 and November 2007.
      Surgery was indicated for patients meeting the following three conditions: a
      serum intact PTH (iPTH) level of 500 pg/ml or more; a maximum glandular volume of
      500 mm3 or more; and increased bone metabolism. Before surgery, we detected the
      parathyroid glands using US, and three-dimensionally measured their sizes. PTx
      was performed based on US diagnosis, and resected glands were weighed. RESULTS:
      Assuming that four parathyroid glands are present in each patient, the total
      number of glands in the 44 patients was 176. Of the 176 glands, 139 were detected
      on preoperative US. However, 27 could not be resected. Therefore, the detection
      rate on US was 63.6% (112/176). Of 37 glands that could not be detected on
      preoperative US, 30 were detected during surgery, and resected. There was a
      positive correlation between the glandular volume measured on US and isolated
      gland weight. However, there was no correlation between the preoperative serum
      iPTH level and the sum of the four isolated gland weights. CONCLUSION: On
      preoperative US, approximately 80% of the glands were detected. However, the
      misdiagnosis rate was approximately 20%. The rate of accurate diagnosis was
      63.6%. Even when glands were misdiagnosed or could not be confirmed on
      preoperative US, approximately 80% of them could be detected and resected during
      surgery. It may be impossible to estimate the glandular volume based on the
      preoperative serum iPTH level.

PMID- 19111414
TI  - Changes in caloric responses after temporal bone surgery with posterior
      tympanotomy.
AB  - OBJECTIVE: To elucidate the role of facial recess bony plate in the thermal
      transmission route from external auditory canal to lateral semicircular canal
      during caloric stimulation test, we performed the test on patients before and
      after removal of the plate, i.e. posterior tympanotomy. In the present study, we
      adopted facial nerve decompression (FND) as posterior tympanotomy without surgery
      induced inner ear damages and cochlear implantation (CI) as posterior tympanotomy
      with surgery-induced inner ear damages. METHODS: Between 1999 and 2003, we
      performed FND on 19 patients with unilateral facial nerve paresis due to Bell's
      palsy (n=7), Ramsay-Hunt syndrome (n=7) or facial nerve trauma (n=5) at Osaka
      Rosai Hospital. We also performed CI on 34 patients with bilateral deafness at
      Osaka University Hospital. To examine effects of FND or CI on caloric responses
      in vestibular periphery, caloric stimulation (30 degrees C cold water and 44
      degrees C hot water) with ENG was performed twice, just before and 6 months after
      surgery in each subject. The caloric-induced nystagmus was recorded by using ENG
      under dark and open-eyes situation to calculate the maximum slow phase eye
      velocity. RESULTS: In cases of FND (n=19), there were significant decreases
      between pre- and post-operative 30 degrees C responses (t-test: p=0.049<0.05).
      There were no significant differences between pre- and post-operative 44 degrees
      C responses (t-test: p=0.467>0.05). In cases of CI (n=34), there were significant
      changes between pre and post-operative responses in both temperatures (t-test:
      p<0.0001 in 30 degrees C; p=0.011<0.05 in 44 degrees C). CONCLUSION: The
      insertion of electrodes during CI did some damages to vestibular peripheral
      function and reduced both hot and cold caloric responses according to the results
      of CI. However, the procedure during posterior tympanotomy could also decrease
      caloric responses especially in cold stimulation according to the results of FND.
      Therefore, we should consider the effect of structural change in temporal bone on
      the thermal transmission in case of evaluation of vestibular peripheral function
      by using caloric stimulation test.

PMID- 19111415
TI  - Investigation of oxidative stress in patients with chronic tonsillitis.
AB  - OBJECTIVES: Oxidative stress has been implicated in numerous pathological
      conditions including chronic tonsillitis. The aim of this study was to assess
      levels of lipid peroxidation, evidenced by formation of thiobarbituric acid
      reactive substance (TBARS), level of total sulfhydryl groups (TSH), and carbonyl
      content in patients with tonsillar hypertrophy (TH) and recurrent tonsillitis
      (RT), before and after tonsillectomy. METHODS: In this study the serum and
      tonsillar tissue levels of TBARS, TSH and carbonyl content were investigated in
      35 patients with TH and RT, before and 1 month after the operation, compared to
      30 age-matched controls. RESULTS: In both TH and RT groups, a significantly
      higher serum TBARS levels were observed before and 4 weeks after tonsillectomy in
      comparison with healthy subjects. The serum level in TH patients after operation
      was even higher compared to the levels before. There was statistically
      significant difference in serum TSH levels between patients with RT before
      operation compared to the control group. After tonsillectomy the serum levels of
      TSH were higher compared to control groups and TH and RT patients before
      operation. Carbonyl content was attenuated only in TH patients after
      tonsillectomy. In tonsillar tissue, significantly lower level of glutathione
      content (GSH) has been observed in RT related to TH patients. CONCLUSIONS:
      Oxidative stress, in patients with tonsillar hypertrophy and recurrent
      tonsillitis, is still present 1 month after the removal of tonsillar tissue.
      Antioxidant therapy, during the recovery period after tonsillectomy, could be
      optional treatment.

PMID- 19111416
TI  - [Vaccinations for the traveling adult solid organ transplant recipient (excluding
      hematopoietic stem cell transplant recipients)].
AB  - Progress in transplantation technique has offered a growing number of solid organ
      transplant recipients the opportunity to travel to tropical and low-income
      countries. The issue of vaccine-preventable diseases is a challenging question in
      immunocompromised patients including those with solid organ transplant. Since the
      response to vaccines is weakened in case of chronic organ failure, candidates
      should be vaccinated early in the course of the disease. Clinicians should
      implement a vaccinal strategy until the patient is scheduled for transplantation
      and monitor its efficacy by serological assays. Live attenuated vaccines (such as
      yellow fever, measles-mumps-rubella, or chicken pox) are contra-indicated in
      solid organ transplant recipients and, when indicated, should be administered
      prior to transplantation, particularly in foreign-born patients highly likely to
      visit friends and relatives in endemic areas. Vaccinations for transplant
      recipients considering international travel should be realized according to the
      risk of acquiring vaccine-preventable diseases but also on both tolerance and
      immune response which are affected by degree and duration of immunosuppression,
      comorbidities, and type of organ transplanted. Routine and specific vaccinations
      for solid organ transplant recipients, as well as travel-related vaccination
      (such as hepatitis A, typhoid, meningococcal meningitis, rabies, tick-born
      encephalitis, Japanese encephalitis, and cholera) should be considered during a
      specific pretravel medical consultation. However, vaccination should be avoided
      in the 6 months following transplantation when patients are usually receiving the
      highest doses of immunosuppressive drugs. In this comprehensive review, we
      provide vaccination schedules based on published studies and guidelines for
      vaccination of solid organ transplant recipients.

PMID- 19111417
TI  - [Metallo-beta-lactamases producing Pseudomonas aeruginosa in Algeria].

PMID- 19111418
TI  - [Diffuse biliary papillomatosis: a rare indication for liver transplantation].

PMID- 19111419
TI  - Hemobilia due to pseudoaneurysm of the cystic artery.

PMID- 19111420
TI  - [Indications and results of liver transplantation (excluding hepatocellular
      carcinoma and fulminant hepatitis)].

PMID- 19111421
TI  - [Liver transplantation for fulminant hepatitis].

PMID- 19111422
TI  - A new moderately thermophilic and high sulfide tolerant biotype of Marichromatium
      gracile, isolated from tidal sediments of the German Wadden Sea: Marichromatium
      gracile biotype thermosulfidiphilum.
AB  - A purple sulfur bacterium, strain SW26, was isolated in pure culture from
      intertidal sediments from the Sylt-Romo Basin, German Wadden Sea, sharing many
      properties with validated Marichromatium species, but differing significantly by
      possessing a plasmid, by tolerating up to 16mM sulfide, and up to 44 degrees C
      for growth. Strain SW26 has a DNA base composition of 68.3mol% G+C, a 16S rRNA
      gene sequence similarity of >99% to those of Marichromatium species, and shows
      the highest level of genomic relationship with Marichromatium gracile, despite
      its remarkably different phenotypic characters. Based upon high genomic
      similarity but different physiological properties of strain SW26 with respect to
      the type strain of M. gracile, a novel biotype, designated as M. gracile biotype
      thermosulfidiphilum is described.

PMID- 19111424
TI  - The prevalence of methicillin-resistant Staphylococcus aureus on inanimate
      objects in an Urban Emergency Department.
AB  - BACKGROUND: There is a rising prevalence of both hospital-acquired and community
      associated strains of methicillin-resistant Staphylococcus aureus (MRSA)
      infections. Both strains are found in patients presenting to emergency
      departments (EDs). OBJECTIVE: The purpose of this study was to identify objects
      in the ED that might contribute to the spread of MRSA. METHODS: This was a cross
      sectional prevalence study in which culture swabs were taken from 20 different
      objects in a large urban ED between May and August 2006. The objects were
      identified a priori, and included common items found in an ED. Items ranging from
      computers to telephones, desktop surfaces, security door keypads, and ultrasound
      probes were included in the study. Each item was cultured twice, on separate
      days, for a total of 40 samples. The samples were screened for the presence of
      MRSA, and positive samples underwent additional susceptibility analysis. RESULTS:
      Only one sample of 40, from the ambulance bay security door keypad, was positive
      for MRSA. Thus, the prevalence of MRSA was 2.5%. The single strain isolated was
      resistant to clindamycin, erythromycin, oxacillin, and penicillin. CONCLUSION:
      MRSA does not seem to thrive on inanimate objects found in the ED. Routine
      cleaning measures in an urban ED must include all areas of medical personnel use,
      including areas outside of the department utilized by non-ED workers.

PMID- 19111423
TI  - Development and validation of an anion-exchange LC-UV method for the
      quantification and purity determination of the DNA plasmid pDERMATT.
AB  - The pDERMATT (plasmid DNA encoding recombinant MART-1 and tetanus toxin fragment
      c) plasmid is a novel in-house developed anti-cancer vaccine which encodes a
      melanoma associated epitope (Mart-1) and an immuno stimulatory sequence (tetanus
      toxin fragment-c). The pharmaceutical development of pDERMATT necessitated the
      availability of an assay for the quantification and purity determination of
      pDERMATT active pharmaceutical ingredient (API), the produced bulk drug and its
      pharmaceutical dosage form. An anion-exchange liquid chromatographic method (AEX
      LC) with ultraviolet (UV) detection was developed, which is based on separation
      on a non porous anion-exchange (NPR AEX) column with a mobile phase gradient of
      0.45-0.53M NaCl in 20mM Tris-HCl 10% isopropanol (IPA) pH 9 and UV detection at
      260 and 280nm. The method was found to be precise, accurate and linear over a
      concentration range of 5-150microg/ml. The supercoiled topoisoform of pDERMATT
      was well separated from the linear and open-circular form, the main degradation
      products formed during stress testing, confirming its stability-indicating
      capability. The use of photo diode array (PDA) detection enabled us to confirm
      all visible peaks to contain DNA. Additionally capillary gel electrophoresis
      (CGE) showed the same peak profile as the developed HPLC method. The developed LC
      UV method will be used for the pharmaceutical quality control of pDERMATT API,
      bulk drug and its pharmaceutical dosage form.

PMID- 19111425
TI  - Catastrophic gastrointestinal injury due to battery acid ingestion.
AB  - BACKGROUND: Acids account for 20% of all chemical exposures through various
      routes. Caustic acids such as hydrochloric and sulfuric acid are common
      ingredients in many household and industrial products. Due to the corrosive
      properties of these substances, tissue injury caused by oral exposure can lead to
      severe esophageal and gastrointestinal burns. CASE REPORT: We report a case of a
      patient presenting with severe acidosis, who required multiple laparoscopic
      evaluations to assess various gastrointestinal tract injuries and who ultimately
      underwent total gastrectomy. The diagnosis was made primarily based on the
      arterial blood gas and esophagogastroduodenoscopy findings, as well as the
      pathological examinations of various biopsied and resected tissues showing
      hemorrhagic necrosis of the esophagus, stomach, and small bowel. This patient
      eventually admitted to having ingested an unspecified amount of battery acid.
      CONCLUSIONS: Collaborative efforts by Emergency Medicine, Pathology, and General
      Surgery services are required for timely diagnosis, treatment, and management of
      patients after caustic acid exposures.

PMID- 19111426
TI  - Use of emergency department transcranial Doppler assessment of reperfusion after
      intravenous tPA for ischemic stroke.
AB  - BACKGROUND: Thrombolysis with intravenous recombinant tissue plasminogen
      activator (IV-tPA) has been associated with significant improvements in clinical
      outcomes when initiated within 3 h of symptom onset. Although adjunctive
      therapies for acute stroke have been developed, challenges remain in identifying
      appropriate patients and therapeutic end-point measurements. OBJECTIVE: To
      describe the use of transcranial Doppler (TCD) monitoring in the Emergency
      Department (ED) to guide the decision for advanced reperfusion strategies after
      failure of IV-tPA. CASE REPORT: A 75-year-old man presented to the ED within 50
      min after the acute onset of right-sided hemiparesis and aphasia. After
      administration of IV-tPA, there was no immediate improvement in neurological
      symptoms. TCD performed in the ED demonstrated persistent left middle cerebral
      artery (MCA) occlusion. Based on this information, the patient received intra
      arterial tPA followed by mechanical thrombectomy of the MCA occlusion, resulting
      in clinical improvement of the patient's right hemiparesis and aphasia.
      CONCLUSION: TCD is a feasible assessment tool for use in the ED to aid in
      diagnosis and to guide treatment decisions in patients with acute ischemic
      stroke, including those not responding to IV-tPA therapy.

PMID- 19111427
TI  - Emergency department presentation of superior mesenteric artery syndrome: two
      cases in Marine Corps recruits.
AB  - BACKGROUND: Superior mesenteric artery (SMA) syndrome is a relatively rare
      etiology of proximal intestinal obstruction. Obstruction results from marked
      narrowing of the angle between the SMA and aorta, causing compression of the
      third portion of the duodenum, most commonly as a result of precipitous weight
      loss. Intermittent non-specific symptoms at presentation often result in a
      delayed diagnosis, thus the importance of being aware of this condition.
      OBJECTIVE: To familiarize emergency physicians with the presentation of SMA
      syndrome and discuss its diagnosis and management in the emergency department
      (ED). CASE REPORT: We present two cases of SMA syndrome identified in Marine
      Corps recruits presenting to our ED. CONCLUSION: Emergency physicians should
      include SMA syndrome in the differential diagnosis of abdominal pain and vomiting
      in individuals with predisposing factors.

PMID- 19111428
TI  - External monitoring-induced pacemaker-driven tachycardia: a case report.
AB  - A 55-year-old African-American woman with a history of end-stage renal disease
      secondary to systemic lupus erythematosus, dual-chamber pacemaker placement
      secondary to sick sinus syndrome, and a previous subarachnoid hemorrhage
      presented via ambulance to our Emergency Department (ED) from an outside hospital
      with the report of altered mental status, hyperkalemia, and hypoglycemia. In the
      ED, the patient's initial physical examination revealed a stable, normal heart
      rate. Reassessment after placement of external monitoring devices found the
      patient to be tachycardic at approximately 132-135 beats/min, with minimal
      variation in rate. The patient was also tachypneic during this episode, up to a
      respiratory rate of 38 breaths/min. When misplaced external monitoring device
      leads were removed during pacemaker interrogation, the patient's heart rate
      dropped to the 70s. Reapplication of the external monitoring leads replicated the
      tachycardia. With permanent repositioning of the leads in the ED, the tachycardia
      did not return. The placement of the leads was determined to have caused a
      plethysmography-induced pacemaker-driven tachycardia.

PMID- 19111429
TI  - Psychoeducation with patients at-risk for schizophrenia--an exploratory pilot
      study.
AB  - OBJECTIVE: To introduce a psychoeducational program for patients of at-risk
      mental state and its preliminary evaluation. METHODS: The psychoeducational
      program was designed as a purely informative intervention and consisted of seven
      1-h sessions. Sixteen at-risk mental state patients (mean age 26+/-4.9 years, 12
      males/4 females, mean score on prodromal psychopathology (Bonn Scale for
      Assessment of predictive Basis Symptoms [BSABS-P] 18.6+/-13.3) were investigated.
      RESULTS: Comparisons of means before and after psychoeducation showed a
      significant reduction in psychopathology and fatalistic LoC as well as an
      improvement in knowledge, global functioning and various areas of QoL. A
      qualitative evaluation of the psychoeducational program also showed advantages
      from patients' perspectives. CONCLUSIONS: This study provides empirical evidence
      for benefits of psychoeducation with patients of at-risk mental state for
      schizophrenia but is exploratory and has some limitations, e.g. the small sample
      size. Therefore the results have to be replicated in a randomized controlled
      trial in order to be able to demonstrate conclusively the effectiveness of
      psychoeducation in the pre-psychotic phase. PRACTICE IMPLICATIONS: Results from
      this preliminary study suggest that psychoeducation is a promising intervention
      for patients of at-risk mental state for schizophrenia, and therefore worthy of
      more investigations.

PMID- 19111430
TI  - Outcome in relation to numbers of nodes harvested in lymph node-positive gastric
      cancer.
AB  - AIMS: We conducted a retrospective case-control study to compare the prognostic
      differences of lymph node-positive gastric cancer patients between dissected
      lymph nodes (DLNs) <15 group and DLNs > or =15 group. METHODS: A retrospective
      study of 323 lymph node-positive gastric patients who underwent potentially
      curative resection for gastric cancer was analyzed to identify the prognostic
      differences between DLNs <15 group and DLNs > or =15 group. Of these patients, 49
      patients with <15 DLNs were matched with 147 patients with > or =15 DLNs
      according to gender, age, location of primary tumor, and type of gastrectomy.
      RESULTS: Patients with n1 lymph node metastasis (according to JCGC), serosal
      involvement, ratio of positive lymph nodes less than 25%, or without adjuvant
      chemotherapy in > or =15 DLN group had comparatively longer median survival than
      patients with homologous clinicopathologic variables in <15 DLN group,
      respectively. Patients with n1 stage lymph node metastasis, serosal involvement,
      non-intestinal Lauren classification, or without adjuvant chemotherapy in <15 DLN
      group had higher recurrence rate than patients with homologous clinicopathologic
      variables in > or =15 DLN group, respectively. In addition, we demonstrated that
      patients with more than n1 stage lymph node metastasis in <15 DLN group had
      higher rate of peritoneal dissemination than those with more than n1 lymph node
      metastasis in > or =15 DLN group. CONCLUSIONS: DNL > or =15 was an important
      factor to improve the prognosis of lymph node-positive gastric cancer patients
      after potential curative resection.

PMID- 19111431
TI  - [Extracorporeal membranous oxygenation in severe infant pertussis: a case
      report].
AB  - Pertussis is a leading cause of death from community infections in infant. Life
      threatening clinical presentations of pertussis can associate multiple organ
      system failure with respiratory distress. The question of the optimal management
      of these severe forms of pertussis, in order to reduce the high mortality rate,
      is raised by the clinicians caring for such patients. We report the case of a 1
      month infant who was admitted to the pediatric intensive care unit (PICU) for a
      severe pertussis. He presented with an acute respiratory distress syndrome, a
      severe pulmonary hypertension was treated initially with mechanical ventilation
      and nitric oxide. At day 4 (D4), a cardiogenic shock occurred and, despite
      epinephrine and norepinephrine infusion, fluid expansion, the hemodynamic
      condition worsened with two episodes of cardiac arrest. The child was then
      successfully resuscitated, and, facing the extreme hemodynamic instability,
      extracorporeal membrane oxygenation (ECMO) was considered. ECMO allowed
      epinephrine and norepinephrine to be progressively discontinued, and protective
      mechanical ventilation. ECMO withdrawal was possible at D9, with milrinone as the
      sole inotropic agent. Weaning from mechanical ventilation was possible on D15 and
      the total length of stay in PICU was 20days. While the analysis of the
      literature, through limited experiences on the use of ECMO in children with
      severe pertussis does not allow concluding definitively on the utility of ECMO in
      this situation, the contribution of ECMO in the favourable outcome for our
      patient was considerable. This is an argument, to our opinion, for considering
      ECMO in the management of those very instable patients.

PMID- 19111432
TI  - [Peripartum cardiomyopathy: incidence, pathogenesis, diagnosis, treatment and
      prognosis].
AB  - INTRODUCTION: Peripartum cardiomyopathy (PPCM) is a rare and life-threatening
      disease of unknown aetiology. The primary objective of this review was to
      analysed aetiopathogeneses, clinical presentation and diagnosis, as well as
      pharmacological, perioperative and intensive care management and prognosis of
      this pathology. METHODS: We undertook a systematic review of the literature using
      Medline, Google Scholar and PubMed searches. RESULTS: Unlike other parts of the
      world in which cardiomyopathy are rare, dilated cardiomyopathy is a major cause
      of heart failure throughout Africa. Its aetiopathogenesis is still poorly
      understood, but recent evidence supports inflammation, viral infection and
      autoimmunity as the leading causative hypotheses. This diagnosis should be
      limited to previously healthy women who present with congestive heart failure
      (CHF) and decreased left ventricular systolic function in the last month of
      pregnancy or within 5 months after delivery. Recently, introduction of
      echocardiography has made diagnosis of PPCM easier and more accurate.
      Conventional treatment consists of diuretics, vasodilators, and sometimes digoxin
      and anticoagulants, usually in combination. Patients who fail to recover may
      require inotropic therapy. In resistant cases, newer therapeutic modalities such
      as immunomodulation, immunoglobulin and immunosuppression may be considered.
      Prognosis is highly related to reversal of ventricular dysfunction. Compared to
      historically higher mortality rates, recent reports describe better outcome,
      probably because of advances in medical care. Based on current information,
      future pregnancy is usually not recommended in patients who fail to recover
      normal heart function. CONCLUSION: PPCM is a rare but serious form of cardiac
      failure affecting women in the last months of pregnancy or early puerperium. Its
      aetiopathogenesis is still poorly understood. Introduction of echocardiography
      has made diagnosis of PPCM easier and more accurate. Prognosis is highly related
      to reversal of ventricular dysfunction.

PMID- 19111433
TI  - [Risk of fungal disease during systemic diseases].
AB  - Invasive fungal diseases are sparse but responsible for a high mortality. During
      systemic diseases, they are less common than bacterial infection but are probably
      underdiagnosed. Diagnosis of invasive fungal disease might be difficult: clinical
      signs may mimic systemic diseases, uninvasive diagnostic tools have not been
      evaluated in this situation and invasive exploration (histology) is rarely done.
      Guidelines for invasive fungal disease curative treatment are available but
      preventive strategies need to be evaluated in the population of patients with
      systemic diseases.

PMID- 19111434
TI  - [Early complications after insertion of pacemaker].

PMID- 19111435
TI  - [Statins: hepatotoxicity and monitoring].
AB  - Statins are among the most widely prescribed drugs throughout the industrialized
      world. Their benefits in primary and secondary prevention of cardiovascular
      events are undeniable. An asymptomatic increase in aminotransferase levels,
      generally less than 3 times the upper limit of normal range, is often observed in
      patients receiving statins. It is dose-dependent and often regresses even though
      treatment continues. A significant increase in aminotransferase levels is very
      rare in patients receiving statins Cases of hepatocellular, cholestatic, and
      mixed pattern liver injuries have been described, but severe hepatitis is rare.
      Cases mimicking autoimmune hepatitis have been described. There is usually no
      cross hepatotoxicity between the different statins. When indicated, statins may
      be used in patients with nonalcoholic fatty liver, chronic viral hepatitis or
      compensated cirrhosis. Statins should not be used in patients with decompensated
      cirrhosis.

PMID- 19111436
TI  - Variations of jitter and shimmer among women in menacme and postmenopausal women.
AB  - The objective of the study was to analyze comparatively the jitter and shimmer
      values of spoken voice among women in menacme and menopausal women using or not
      hormonal replacement therapy (HRT). Forty-five women were studied, divided into
      the following groups: Control Group (CG), 15 women aged 20-40 years with regular
      menstrual cycles who did not take hormonal contraceptives; Treated Group (TG), 15
      women aged 45-60 years with at least 2 years of menopause, under continuous HRT
      with 1 mg estradiol valerate + 90 microg norgestimate per day for at least 6
      months; Untreated Group (UG), 15 women aged 45-60 years with at least 2 years of
      menopause who did not use HRT. Mean age was 30.3, 54.5, and 56.5 years for CG,
      TG, and UG, respectively. All subjects were submitted to acoustic analysis of
      jitter and shimmer for the sustained vowels /e/ and /i/. Mean jitter values were
      0.56%, 0.64%, and 0.56% for the vowel /e/ and 0.88%, 0.79%, and 0.68% for the
      vowel /i/ for CG, TG, and UG, respectively. Mean shimmer values were 4.17%,
      4.38%, and 4.77% for the vowel /e/ and 5.19%, 4.59%, and 5.37% for the vowel /i/
      for CG, TG, and UG, respectively. There were no significant differences between
      the groups studied. The results obtained here by the methodology used suggest
      that there were no significant differences in jitter and shimmer when we assessed
      the sustained vowels /i/ and /e/ between menopausal women using or not HRT or
      between young and menopausal women treated or not.

PMID- 19111437
TI  - Maximum phonation time: variability and reliability.
AB  - The objective of the study was to determine maximum phonation time reliability as
      a function of the number of trials, days, and raters in dysphonic and control
      subjects. Two groups of adult subjects participated in this reliability study: a
      group of outpatients with functional or organic dysphonia versus a group of
      healthy control subjects matched by age and gender. Over a period of maximally 6
      weeks, three video recordings were made of five subjects' maximum phonation time
      trials. A panel of five experts were responsible for all measurements, including
      a repeated measurement of the subjects' first recordings. Patients showed
      significantly shorter maximum phonation times compared with healthy controls (on
      average, 6.6 seconds shorter). The averaged interclass correlation coefficient
      (ICC) over all raters per trial for the first day was 0.998. The averaged
      reliability coefficient per rater and per trial for repeated measurements of the
      first day's data was 0.997, indicating high intrarater reliability. The mean
      reliability coefficient per day for one trial was 0.939. When using five trials,
      the reliability increased to 0.987. The reliability over five trials for a single
      day was 0.836; for 2 days, 0.911; and for 3 days, 0.935. To conclude, the maximum
      phonation time has proven to be a highly reliable measure in voice assessment. A
      single rater is sufficient to provide highly reliable measurements.

PMID- 19111438
TI  - Perception of emotional valences and activity levels from vowel segments of
      continuous speech.
AB  - This study aimed to investigate the role of voice source and formant frequencies
      in the perception of emotional valence and psychophysiological activity level
      from short vowel samples (approximately 150 milliseconds). Nine professional
      actors (five males and four females) read a prose passage simulating joy,
      tenderness, sadness, anger, and a neutral emotional state. The stress carrying
      vowel [a:] was extracted from continuous speech during the Finnish word
      [ta:k:ahan] and analyzed for duration, fundamental frequency (F0), equivalent
      sound level (L(eq)), alpha ratio, and formant frequencies F1-F4. Alpha ratio was
      calculated by subtracting the L(eq) (dB) in the range 50 Hz-1 kHz from the L(eq)
      in the range 1-5 kHz. The samples were inverse filtered by Iterative Adaptive
      Inverse Filtering and the estimates of the glottal flow obtained were
      parameterized with the normalized amplitude quotient (NAQ = f(AC)/(d(peak)T)).
      Fifty listeners (mean age 28.5 years) identified the emotional valences from the
      randomized samples. Multinomial Logistic Regression Analysis was used to study
      the interrelations of the parameters for perception. It appeared to be possible
      to identify valences from vowel samples of short duration ( approximately 150
      milliseconds). NAQ tended to differentiate between the valences and activity
      levels perceived in both genders. Voice source may not only reflect variations of
      F0 and L(eq), but may also have an independent role in expression, reflecting
      phonation types. To some extent, formant frequencies appeared to be related to
      valence perception but no clear patterns could be identified. Coding of valence
      tends to be a complicated multiparameter phenomenon with wide individual
      variation.

PMID- 19111439
TI  - Laryngeal electromyography: clinical application.
AB  - Laryngeal electromyography (LEMG) is a valuable adjunct in clinical management of
      patients with voice disorders. LEMG is valuable in differentiating vocal fold
      paresis/paralysis from cricoarytenoid joint fixation. Our data indicate that
      visual assessment alone is inadequate to diagnose neuromuscular dysfunction in
      the larynx and that diagnoses based on vocal dynamics assessment and
      strobovideolaryngoscopy are wrong in nearly one-third of cases, based on LEMG
      results. LEMG has also proven valuable in diagnosing neuromuscular dysfunction in
      some dysphonic patients with no obvious vocal fold movement abnormalities
      observed during strobovideolaryngoscopy. Review of 751 patients suggests that
      there is a correlation between the severity of paresis and treatment required to
      achieve satisfactory outcomes; that is, LEMG allows us to predict whether
      patients will probably require therapy alone or therapy combined with surgery.
      Additional evidence-based research should be encouraged to evaluate efficacy
      further.

PMID- 19111440
TI  - Vocal fold surface hydration: a review.
AB  - Vocal fold surface liquid homeostasis contributes to optimal vocal physiology. In
      this paper we review emerging evidence that vocal fold surface liquid is
      maintained in part by salt and water fluxes across the epithelium. Based on
      recent immunolocalization and electrophysiological findings, we describe a
      transcellular pathway as one mechanism for regulating superficial vocal fold
      hydration. We propose that the pathway includes the sodium-potassium pump, sodium
      potassium-chloride cotransporter, epithelial sodium channels, cystic fibrosis
      transmembrane regulator chloride channels, and aquaporin water channels. By
      integrating knowledge of the regulating mechanisms underlying ion and fluid
      transport with observations from hydration challenges and treatments using in
      vitro and in vivo studies, we provide a theoretical basis for understanding how
      environmental and behavioral challenges and clinical interventions may modify
      vocal fold surface liquid composition. We present converging evidence that
      clinical protocols directed at facilitating vocal fold epithelial ion and fluid
      transport may benefit healthy speakers, those with voice disorders, and those at
      risk for voice disorders.

PMID- 19111441
TI  - Laryngeal amyloidosis causing hoarseness and airway obstruction.
AB  - Amyloidosis constitutes a fraction of 1% of benign localized laryngeal tumors and
      may occasionally be associated with systemic disease. A chronic, insidious,
      progressive, recurrent disease characterized by hoarseness, dyspnea, and stridor,
      it is caused by extracellular deposition of insoluble, abnormal tissue injurious
      fibrils. Submucosal lesions occur frequently in the vestibular folds and
      ventricles, less commonly in the subglottis and aryepiglottic folds and least on
      the vocal folds. Apple green birefrigence under polarized light after Congo red
      staining, electron microscopic fibrillar structure, and a beta-pleated sheet
      structure observed by x-ray diffraction are confirmatory. Two presented cases add
      to the small literature review of similar patients. Case 1 was a 70-year-old man
      with severe hoarseness, incomplete glottic closure, ovoid concentric stenosis of
      the inferior glottis and subglottis, who initially was not diagnosed by several
      laryngologists and speech therapists. He required multiple microlaryngoscopic
      excisions and dilations. Because low dose radiation induces plasma cell apoptosis
      in other diseases, external beam radiation therapy (EBRT) was hypothesized to
      eliminate amyloidogenic plasma cells. Case 2 was a 46-year-old welder with
      progressive dyspnea for 2-3 years and hoarseness, voice loss, and stridor over 6
      7 months. Masses caused airway obstruction of the anterior commissure,
      vestibular, and vocal folds, with extension to the subglottis. Two
      phonomicrosurgical CO(2) laser-assisted resections relieved upper airway
      obstruction and restored voice. Conservative surgical intervention and long-term
      followup are essential. Further studies are needed to determine if a radiation
      dose response relationship exists to control laryngeal amyloidosis.

PMID- 19111442
TI  - Morphological and wavelet features towards sonographic thyroid nodules
      evaluation.
AB  - This paper presents a computer-based classification scheme that utilized various
      morphological and novel wavelet-based features towards malignancy risk evaluation
      of thyroid nodules in ultrasonography. The study comprised 85 ultrasound images
      patients that were cytological confirmed (54 low-risk and 31 high-risk). A set of
      20 features (12 based on nodules boundary shape and 8 based on wavelet local
      maxima located within each nodule) has been generated. Two powerful pattern
      recognition algorithms (support vector machines and probabilistic neural
      networks) have been designed and developed in order to quantify the power of
      differentiation of the introduced features. A comparative study has also been
      held, in order to estimate the impact speckle had onto the classification
      procedure. The diagnostic sensitivity and specificity of both classifiers was
      made by means of receiver operating characteristics (ROC) analysis. In the
      speckle-free feature set, the area under the ROC curve was 0.96 for the support
      vector machines classifier whereas for the probabilistic neural networks was
      0.91. In the feature set with speckle, the corresponding areas under the ROC
      curves were 0.88 and 0.86 respectively for the two classifiers. The proposed
      features can increase the classification accuracy and decrease the rate of
      missing and misdiagnosis in thyroid cancer control.

PMID- 19111443
TI  - Review of methods for functional brain connectivity detection using fMRI.
AB  - Since the mid of 1990s, functional connectivity study using fMRI (fcMRI) has
      drawn increasing attention of neuroscientists and computer scientists, since it
      opens a new window to explore functional network of human brain with relatively
      high resolution. A variety of methods for fcMRI study have been proposed. This
      paper intends to provide a technical review on computational methodologies
      developed for fcMRI analysis. From our perspective, these computational methods
      are classified into two general categories: model-driven methods and data-driven
      methods. Data-driven methods are a large family, and thus are further sub
      classified into decomposition-based methods and clustering analysis methods. For
      each type of methods, principles, main contributors, and their advantages and
      drawbacks are discussed. Finally, potential applications of fcMRI are overviewed.

PMID- 19111444
TI  - Transoral endoscopic-assisted management of subcondylar fractures in 17 patients:
      an alternative to open reduction with rigid internal fixation and closed
      reduction with maxillomandibular fixation.
AB  - The authors evaluate the results of transoral endoscopic-assisted open reduction
      and miniplate fixation of subcondylar fractures. Seventeen patients were treated
      from August 2005 to April 2007. Inclusion criteria were: adult patients,
      inability to achieve adequate occlusion with closed reduction, dislocation of the
      condylar fragment between 10 and 45 degrees , and 2-mm inter-fragment
      overlapping. Regular panoramic radiographs were taken postoperatively.
      Transbuccal incisions were used to place the screws for fixation in 15 patients.
      Pure intraoral access and angulated drills and screwdrivers were used in 2
      patients. The condyle was placed into the condylar fossa in all cases. No damage
      to the facial nerve was observed. No visible scars were present. Mean surgical
      time was 80.36 minutes. Transitory hyposthesia was observed in 3 cases. Adequate
      reduction and consolidation of the fracture was achieved in 16 patients. No
      condylar reabsortion was present at the end of the follow-up period. The authors
      consider that transoral endoscopic-assisted open reduction constitutes a valid
      alternative to a transcutaneous approach for the reduction and fixation of
      subcondylar fractures in selected cases. It provides the benefits of open
      reduction and internal fixation without the potential complications. Advice is
      given on how to achieve adequate reduction and stability of the proximal
      fragment.

PMID- 19111445
TI  - No involvement of non-synonymous TLR2 polymorphisms in Japanese leprosy patients.

PMID- 19111446
TI  - An in vitro analysis of mechanical wounding-induced ligand-independent KGFR
      activation.
AB  - BACKGROUND: KGFR (keratinocyte growth factor receptor), exclusively expressed in
      epithelial cells, plays an important role in wound healing. However, mechanisms
      of KGFR activation and signaling in wound healing are not clearly understood.
      OBJECTIVES: We utilized an in vitro mechanical wounding model to examine ligand
      independent KGFR activation, its regulation by reactive oxygen species (ROS) and
      the functional significance of this activation mechanism. METHODS: Confluent
      HaCaT cell line cultures were mechanically wounded and KGFR internalization and
      phosphorylation were examined using immunostaining with confocal microscopy and
      immunoprecipitation with Western blotting. Wounding-induced generation of
      reactive oxygen species and ligand-independent activation of KGFR were examined.
      In addition, phosphorylation of its associated molecules FRS2 and c-Src were
      examined in the presence and absence of the ROS and pathway specific inhibitors.
      The importance of this activation process on cell migration was also examined in
      the presence and absence of these inhibitors. RESULTS: Mechanical wounding
      induced ligand-independent KGFR activation and internalization. KGFR
      internalization and phosphorylation was associated with ROS generation along the
      wound edge and scavenging of ROS with NAC inhibited KGFR phosphorylation.
      Intracellularly, c-Src was phosphorylated by wounding but its inhibitor, PP1,
      significantly inhibited KGFR activation and associated FRS2 phosphorylation.
      Mechanical wounding induced wound edge migration, which was significantly reduced
      by the selective receptor and pathway inhibitors PP1 (82.7%), KGFR inhibitor
      SU5402 (70%) and MAPK inhibitor PD98059 (57%). CONCLUSION: Mechanical wounding
      induces significant ROS generation at the wound edge which, in turn, induced
      ligand-independent KGFR and FRS2 activation via c-Src kinase signaling.
      Functionally, downstream MAPK signaling induced wound edge cell migration.

PMID- 19111447
TI  - Polyelectrolyte polymer properties in relation to male contraceptive RISUG
      action.
AB  - RISUG a polyelectrolytic hydrogel (styrene maleic anhydride and dimethyl
      sulfoxide) has proven to be efficacious as a contraceptive for a long term when
      injected into the lumen of vas deferens. Currently it is in advanced phase III
      clinical trials in India. Present investigation analyzes the swelling
      characteristics of RISUG hydrogel in different pH buffers and various biological
      fluids to understand its retention in the vas deferens as reported in previous
      studies. Significant variation in degree of swelling and equilibrium swelling
      ratio with transformation of Fickian to non-Fickian mode of diffusion was
      observed with increased pH. This might be due to ionization of carboxylic groups
      at high pH resulting in increased electrostatic repulsive force and high osmotic
      pressure inside the hydrogel network affecting its physical cross-linking and
      increases the free volume. Conversely, at low pH the dissociation of carboxylic
      group is limited making the hydrogel more stable. Interaction with various
      biomolecules present in various biological fluids was also studied. SEM, AFM and
      FTIR were used to analyze the topological and structural parameters of the
      polymer in different mediums. Loosening of structure and increasing porosity with
      significant adsorption of various biomolecules was observed. AFM revealed a
      significant change in overall roughness of polymer surface on interaction with
      different biological fluids. These observations suggest that the swelling and
      increased roughness will lead to increased resistance to sperm movement in the
      vas deferens.

PMID- 19111448
TI  - Modelling treatment effects in a clinical Bayesian network using Boolean
      threshold functions.
AB  - OBJECTIVE: Appropriate antimicrobial treatment of infections in critically ill
      patients should be started as soon as possible, as delay in treatment may reduce
      a patient's prognostic outlook considerably. Ventilator-associated pneumonia
      (VAP) occurs in patients in intensive care units who are mechanically ventilated
      and is almost always preceded by colonisation of the respiratory tract by the
      causative microorganisms. It is very difficult to clinically diagnose VAP and,
      therefore, some form of computer-based decision support might be helpful for the
      clinician. MATERIALS AND METHODS: As diagnosing and treating VAP involves
      reasoning with uncertainty, we have used a Bayesian network as the primary tool
      for building a decision-support system. The effects of usage of antibiotics on
      the colonisation of the respiratory tract by various pathogens and the subsequent
      antibiotic choices in case of VAP were modelled using the notion of causal
      independence. In particular, the conditional probability distribution of the
      random variable that represents the overall coverage of pathogens by antibiotics
      was modelled in terms of the conjunctive effect of the seven different pathogens,
      usually referred to as the noisy-AND model. In this paper, we investigate
      different coverage models, as well as generalisations of the noisy-AND, called
      noisy-threshold models, and test them on clinical data of intensive care unit
      (ICU) patients who are mechanically ventilated. RESULTS: Some of the constructed
      noisy-threshold models offered further improvement of the performance of the
      Bayesian network in covering present causative pathogens by advising appropriate
      antimicrobial treatment. CONCLUSIONS: By reconsidering the modelling of
      interactions between the random variables in a Bayesian network using the theory
      of causal independence, it is possible to refine its performance. This was
      clearly shown for our Bayesian network concerning VAP, indicating that only
      specific noisy-threshold models might be appropriate for the modelling of the
      interaction between pathogens and antimicrobial treatment with respect to
      susceptibility. The results obtained also provide evidence that the noisy-OR and
      noisy-AND might not always be the best functions to model interactions among
      random variables.

PMID- 19111449
TI  - Matching incomplete time series with dynamic time warping: an algorithm and an
      application to post-stroke rehabilitation.
AB  - OBJECTIVE: The purpose of this study was to assess the performance of a real-time
      ("open-end") version of the dynamic time warping (DTW) algorithm for the
      recognition of motor exercises. Given a possibly incomplete input stream of data
      and a reference time series, the open-end DTW algorithm computes both the size of
      the prefix of reference which is best matched by the input, and the dissimilarity
      between the matched portions. The algorithm was used to provide real-time
      feedback to neurological patients undergoing motor rehabilitation. METHODS AND
      MATERIALS: We acquired a dataset of multivariate time series from a sensorized
      long-sleeve shirt which contains 29 strain sensors distributed on the upper limb.
      Seven typical rehabilitation exercises were recorded in several variations, both
      correctly and incorrectly executed, and at various speeds, totaling a data set of
      840 time series. Nearest-neighbour classifiers were built according to the
      outputs of open-end DTW alignments and their global counterparts on exercise
      pairs. The classifiers were also tested on well-known public datasets from
      heterogeneous domains. RESULTS: Nonparametric tests show that (1) on full time
      series the two algorithms achieve the same classification accuracy (p-value
      =0.32); (2) on partial time series, classifiers based on open-end DTW have a far
      higher accuracy (kappa=0.898 versus kappa=0.447;p<10(-5)); and (3) the prediction
      of the matched fraction follows closely the ground truth (root mean square <10%).
      The results hold for the motor rehabilitation and the other datasets tested, as
      well. CONCLUSIONS: The open-end variant of the DTW algorithm is suitable for the
      classification of truncated quantitative time series, even in the presence of
      noise. Early recognition and accurate class prediction can be achieved, provided
      that enough variance is available over the time span of the reference. Therefore,
      the proposed technique expands the use of DTW to a wider range of applications,
      such as real-time biofeedback systems.

PMID- 19111450
TI  - Optimising care of elderly breast cancer patients: a challenging priority.
AB  - Elderly breast cancer patients comprise almost 50% of the breast cancer
      population. The unique needs of this population are discussed. Therapeutic
      challenges facing clinicians include the absence of the ideal method to assess
      these patients' fitness to receive therapy, to anticipate probable side-effects
      and to predict survival. In addition, there are few guidelines to assist decision
      making, as historically clinical trials have excluded such individuals. Evidence
      for the use of chemotherapy, endocrine therapy and newer targeted therapies in
      the elderly is summarised. Special safety considerations in the elderly are
      highlighted and current practice and ongoing research are reviewed.

PMID- 19111451
TI  - Metabolic syndrome and prostate cancer: a review.
AB  - Androgen deprivation therapy is widely used in a number of different settings in
      the treatment of prostate cancer. This overview will look at the current evidence
      for the potential development of metabolic syndrome and cardiovascular disease as
      a consequence of this therapy, and highlight strategies aimed at their
      prevention. The relationship between metabolic syndrome and prostate cancer
      development will also be examined.

PMID- 19111452
TI  - Accelerated radical radiotherapy for non-small cell lung cancer using two common
      regimens: a single-centre retrospective study of outcome.
AB  - AIMS: A variety of radical radiotherapy regimens are in use for non-small cell
      lung cancer. Continuous hyperfractionated accelerated radiotherapy (CHART: 54 Gy
      in 36 fractions over 12 days) and accelerated hypofractionated radiotherapy using
      55 Gy in 20 fractions over 4 weeks are standard fractionations in our centre. The
      primary aim of this retrospective study was to evaluate survival outcome seen in
      routine clinical practice. MATERIALS AND METHODS: All case notes and radiotherapy
      records of radically treated patients between 1999 and 2004 were retrospectively
      reviewed. Basic patient demographics, tumours, characteristics, radiotherapy and
      survival data were collected. RESULTS: In total, 277 patients received radical
      radiotherapy: 137 and 140 patients received CHART and hypofractionated
      radiotherapy, respectively. There were differences noted in the demographics
      between the two treatment schedules: median age 65 years (range 41-83) vs 73
      years (range 33-87); histological confirmation rates 90% vs 76%; prior
      chemotherapy 34% vs 19% for CHART and hypofractionated treatment, respectively.
      For CHART patients, stages I, II, III and unclassified were 12, 8, 68 and 12% and
      the staging for the hypofractionated regimen was 54, 11, 34 and 2%, respectively.
      The median overall survival from the time of diagnosis was 20.4 months with a 40%
      2-year survival rate. For the two fractionations the median survival was 16.6
      months vs 21.4 months and 34% vs 45% of patients were alive at 2 years in the
      CHART and hypofractionated groups, respectively. On multivariate analysis, stage
      was the only factor affecting overall survival - no difference was seen according
      to radiotherapy regimen. CONCLUSION: This single-centre study reflects the
      outcome of unselected consecutively treated non-small cell lung cancer patients.
      Adjusting for stage, there was no significant difference in survival seen
      according to regimen. Encouragingly, CHART outcome shows reproducibility with the
      original CHART paper. Our hypofractionated outcome is similar to that previously
      reported, but despite this being the UK's most common regimen, 55 Gy in 20 daily
      fractions remains unvalidated by phase III trial data.

PMID- 19111453
TI  - Biomass smoke induced bronchial anthracofibrosis: presenting features and
      clinical course.
AB  - BACKGROUND: The presenting features and clinical course of biomass smoke induced
      bronchial anthracofibrosis (BAF) are not well known. PATIENTS AND METHODS: 333
      patients who had a history of long-term exposure to biomass smoke, having BAF
      confirmed by a bronchoscopy from January 1998 to December 2004, were included in
      this study. The clinical features, associated diseases, and clinical outcomes
      were investigated through the analysis of medical records. RESULTS: There were 51
      males (15.3%) and 282 females (84.7%), having a mean age of 72.3 years, ranging
      from 47 to 90. 33% of patients had a past history of pulmonary tuberculosis.
      Dyspnea (38.4%) and cough (29.8%) were most common presenting symptoms, followed
      by hemoptysis (8.9%). Baseline pulmonary function showed mild airflow
      obstruction. Among patients with forced expiratory volume in 1s (FEV(1))/forced
      vital capacity (FVC)<0.7, Global Initiative for Chronic Obstructive Lung Disease
      (GOLD) stages I and II were most common. Associated diseases were active
      tuberculosis in 33.9% of patients, pneumonia in 29.5%, acute exacerbation of
      chronic airways disease in 22.5%, and malignancy in 4.8%. Among the 18 patients
      who died at a hospital during the follow-up period, acute infection and
      malignancy were common causes of death. CONCLUSIONS: These findings suggest that
      biomass smoke induced BAF usually appears clinically as a form of obstructive
      airways disease. Since various pulmonary diseases, including tuberculosis,
      pneumonia, and malignancy, can be associated with BAF, thorough clinical
      evaluation and close follow-up of these patients are required.

PMID- 19111455
TI  - Making residential cannabis growing operations actionable: a critical policy
      analysis.
AB  - BACKGROUND: In 2006, the British Columbia (BC) government passed amendments to
      its Safety Standards Act. These amendments permit the routine disclosure of
      electrical usage information from electrical producers to BC's municipalities,
      ostensibly to identify and eradicate residential cannabis growing operations
      (grow ops). These amendments originated in a pilot project in Surrey, BC, known
      as the electrical and fire safety inspection initiative (EFSI), which drew
      together police, firefighters and others, to identify grow ops through the
      process of municipal electrical inspections. METHODS: This paper draws on
      narrative analysis to critically explore how the report of the EFSI Surrey pilot
      project uses a series of linked claims to generate interpretative change in the
      definition of the problem of grow ops. This analysis also shows how claims about
      grow ops are constructed and gain their potency through links with other social
      problems, persons, and practices. RESULTS: Though the report of the EFSI project
      is a prohibitionist text replete with stock characters and themes from the
      history of Canadian drug policy, the problem of residential cannabis cultivation
      is made actionable by establishing grow operators as "superdeviants" constructed
      both as dangerous outsiders and as risks to a host of public safety concerns.
      These claims are then linked to the notion of an overwhelmed criminal justice
      system that establishes a "crisis" that justifies extraordinary methods of social
      control outside the due process of the criminal justice system. CONCLUSIONS:
      Construction of all cannabis cultivators as "dangerous" disavows other
      possibilities and shores up neo-liberal practices of government that draw on
      multi-partner initiatives to implement extraordinary methods of social control
      not necessarily subject to public accountability.

PMID- 19111456
TI  - Electrochemical biosensing of methyl parathion pesticide based on
      acetylcholinesterase immobilized onto Au-polypyrrole interlaced network-like
      nanocomposite.
AB  - We developed a simple strategy for designing a highly sensitive electrochemical
      biosensor for organophosphate pesticides (OPs) based on acetylcholinesterase
      (AChE) immobilized onto Au nanoparticles-polypyrrole nanowires composite film
      modifid glassy carbon electrode (labeled as AChE-Au-PPy/GCE). Where, the
      generated Au nanoparticles (AuNPs) were homogenously distributed onto the
      interlaced PPy nanowires (PPy NWs) matrix, constructing a three-dimensional
      porous network. This network-like nanocomposite not only provided a biocompatible
      microenvironment to keep the bioactivity of AChE, but also exhibited a strong
      synergetic effect on improving the sensing properties of OPs. The combination of
      AuNPs and PPyNWs greatly catalyzed the oxidation of the enzymatically generated
      thiocholine product, thus increasing the detection sensitivity. On the basis of
      the inhibition of OPs on the enzymatic activity of AChE, the conditions for OPs
      detection were optimized by using methyl parathion as a model OP compound. The
      inhibition of methyl parathion was proportional to its concentration ranging from
      0.005 to 0.12 and 0.5 to 4.5 microgmL(-1). The detection limit was 2 ngmL(-1).
      The developed biosensor exhibited good reproducibility and acceptable stability.
      This study provides a new promise tool for analysis of organophosphate
      pesticides.

PMID- 19111454
TI  - Genetic association analysis of COPD candidate genes with bronchodilator
      responsiveness.
AB  - Airflow limitation in COPD patients is not fully reversible. However, there may
      be large variability in bronchodilator responsiveness (BDR) among COPD patients,
      and familial aggregation of BDR suggests a genetic component. Therefore, we
      investigated the association between six candidate genes and BDR in subjects with
      severe COPD. A total of 389 subjects from the National Emphysema Treatment Trial
      (NETT) were analyzed. Bronchodilator responsiveness to albuterol was expressed in
      three ways: absolute change in FEV(1), change in FEV(1) as a percent of baseline
      FEV(1), and change in FEV(1) as a percent of predicted FEV(1). Genotyping was
      completed for 122 single nucleotide polymorphisms (SNPs) in six candidate genes
      (EPHX1, SFTPB, TGFB1, SERPINE2, GSTP1, ADRB2). Associations between BDR
      phenotypes and SNP genotypes were tested using linear regression, adjusting for
      age, sex, pack-years of smoking, and height. Genes associated with BDR phenotypes
      in the NETT subjects were assessed for replication in 127 pedigrees from the
      Boston Early-Onset COPD (EOCOPD) Study. Three SNPs in EPHX1 (p=0.009-0.04), three
      SNPs in SERPINE2 (p=0.004-0.05) and two SNPs in ADRB2 (0.04-0.05) were
      significantly associated with BDR phenotypes in NETT subjects. One SNP in EPHX1
      (rs1009668, p=0.04) was significantly replicated in EOCOPD subjects. SNPs in
      SFTPB, TGFB1, and GSTP1 genes were not associated with BDR. In conclusion, a
      polymorphism of EPHX1 was associated with bronchodilator responsiveness
      phenotypes in subjects with severe COPD.

PMID- 19111457
TI  - Optimal duration of first-line chemotherapy for advanced non-small cell lung
      cancer: a systematic review with meta-analysis.
AB  - BACKGROUND: The optimal duration of first-line chemotherapy for advanced non
      small cell lung cancer (NSCLC) has been a matter for debate for nearly 20 years.
      In order to elucidate this issue, a meta-analysis comparing the different
      durations of same treatments was performed. METHODS: We searched for all
      published randomised controlled trials (RCTs) comparing different durations of
      first-line treatment of advanced NSCLC. The MEDLINE, EMBASE, LILACS and CENTRAL
      databases were searched for RCTs comparing a defined number of cycles of
      chemotherapy versus continuing treatment until disease progression, or a defined
      number of cycles versus a higher number of cycles of the same chemotherapy.
      Trials including biological agents were excluded. RESULTS: Seven trials that
      included 1559 patients were analysed. Treatment for more than 4 cycles was
      associated with a non-statistically significant decrease in the hazard of
      mortality relative to shorter treatment (hazard ratio (HR)=0.97; 95% confidence
      interval (CI)=0.84-1.11; P=.65). In those treated with third-generation
      chemotherapy through the whole study time, treatment for more than 4 cycles was
      associated with a non-statistically significant increase in mortality (HR=1.08;
      95% CI=0.90-1.28; P=.28). Patients receiving more chemotherapy had significant
      longer progression-free survival (HR=.75; 95% CI=0.60-0.85; P<0.0001) than the
      group with shorter duration of treatment. In an intent-to-treat analysis, there
      was no difference in the overall response rate between the groups (odds ratio
      (OR)=0.78; 95% CI=0.60-1.01; P=.96). Longer treatment was associated with more
      severe leucopaenia but with no significant increase in non-haematological
      toxicities. CONCLUSIONS: In patients with advanced NSCLC the use of more than 4
      cycles of first-line chemotherapy with third-generation regimens significantly
      increases progression-free survival but not overall survival and is associated
      with higher incidence of adverse events. There is no evidence to support
      continuous chemotherapy until progression in patients with lung cancer.

PMID- 19111458
TI  - Comparison between a moving bed membrane bioreactor and a conventional membrane
      bioreactor on organic carbon and nitrogen removal.
AB  - A membrane bioreactor filled with carriers instead of activated sludge named a
      moving bed membrane bioreactor (MBMBR) was investigated for simultaneously
      removing organic carbon and nitrogen in wastewater. Its performance was compared
      with a conventional membrane bioreactor (CMBR) at various influent COD/TN ratios
      of 8.9-22.1. The operational parameters were optimized to increase the treatment
      efficiency. COD removal efficiency averaged at 95.6% and 96.2%, respectively, for
      MBMBR and CMBR during the 4 months experimental period. The MBMBR system
      demonstrated good performance on nitrogen removal at different COD/TN ratios.
      When COD/TN was 8.9 and the total nitrogen (TN) load was 7.58 mg/l h, the TN and
      ammonium nitrogen removal efficiencies of the MBMBR were maintained over 70.0%
      and 80.0%, respectively, and the removed total nitrogen (TN) load reached to 5.31
      mg/l h. Multifunctional microbial reactions in the carrier, such as simultaneous
      nitrification and denitrification (SND), play important roles in nitrogen
      removal. In comparison, the CMBR did not perform so well. Its TN removal was not
      stable, and the removed total nitrogen (TN) load was only 1.02 mg/l h at COD/TN
      ratio 8.9. The specific oxygen utilization rate (SOUR) showed that the biofilm
      has a better microbial activity than an activated sludge. Nevertheless, the
      membrane fouling behavior was more severe in the MBMBR than in the CMBR due to a
      thick and dense cake layer formed on the membrane surface, which was speculated
      to be caused by the filamentous bacteria in the MBMBR.

PMID- 19111459
TI  - Continuous Cr(VI) removal by Scenedesmus incrassatulus in an airlift
      photobioreactor.
AB  - Cr(VI) removal by Scenedesmus incrassatulus was characterized in a continuous
      culture system using a split-cylinder internal-loop airlift photobioreactor fed
      continuously with a synthetic effluent containing 1.0mg Cr(VI) l(-1) at dilution
      rate (D) of 0.3d (-1). At steady state, there was a small increase (6%) on the
      dry biomass (DB) concentration of Cr(VI)-treated cultures compared with the
      control culture. 1.0mg Cr(VI) l(-1) reduced the photosynthetic pigments content
      and altered the cellular morphology, the gain in dry weight was not affected. At
      steady state, Cr(VI) removal efficiency was 43.5+/-1.0% and Cr(VI) uptake was
      1.7+/-0.1 mg Cr(VI) g(-1) DB. The system reached a specific metal removal rate of
      458 microg Cr(VI) g(-1) DB d(-1), and a volumetric removal rate of 132 microg
      Cr(VI) l(-1) d(-1).

PMID- 19111460
TI  - Discovery of potent inhibitors of interleukin-2 inducible T-cell kinase (ITK)
      through structure-based drug design.
AB  - Interleukin-2 inducible T-cell kinase (ITK) is a member of the Tec kinase family
      and is involved with T-cell activation and proliferation. Due to its critical
      role in acting as a modulator of T-cells, ITK inhibitors could provide a novel
      route to anti-inflammatory therapy. This work describes the discovery of ITK
      inhibitors through structure-based design where high-resolution crystal
      structural information was used to optimize interactions within the kinase
      specificity pocket of the enzyme to improve both potency and selectivity.

PMID- 19111461
TI  - Thienopyrimidine-based dual EGFR/ErbB-2 inhibitors.
AB  - Two new series of potent and selective dual EGFR/ErbB-2 kinase inhibitors derived
      from novel thienopyrimidine cores have been identified. Isomeric thienopyrimidine
      cores were evaluated as isosteres for a 4-anilinoquinazoline core and several
      analogs containing the thieno[3,2-d]pyrimidine core showed anti-proliferative
      activity with IC(50) values less than 1 microM against human tumor cells in
      vitro.

PMID- 19111462
TI  - Synthesis and CHK1 inhibitory potency of Hymenialdisine analogues.
AB  - A series of thieno[3,2-b]pyrroloazepinones derivatives related to Hymenialdisine
      were prepared and tested for CHK1 inhibitory activity. Nanomolar inhibitions were
      achieved when electron-withdrawing substituents were introduced at position 3 of
      the thiophene ring.

PMID- 19111463
TI  - Second generation 4-(4-methyl-1H-indol-5-ylamino)-2-phenylthieno[2,3-b]pyridine-5
      carbonitrile PKCtheta inhibitors.
AB  - Thieno[2,3-b]pyridine-5-carbonitrile 16 with a 4-methyl-5-indolylamine at C-4 and
      a 5-methoxy-2-(dimethylamino)-methylphenyl group at C-2 had an IC(50) value of 16
      nM for the inhibition of PKCtheta. While moderate inhibition of PKCdelta was also
      observed (IC(50)=130 nM), 16 had IC(50) values of greater than 5 microM against
      Lyn and other members of the Src kinase family.

PMID- 19111464
TI  - Synthesis and biological activity of novel shikonin analogues.
AB  - A series of shikonin analogues with side chain variants have been synthesized and
      evaluated for antitumor activity. These novel analogues show a broad spectrum of
      in vitro cytotoxicity against various cancer cell lines. Additionally, some
      analogues were also found to have the ability to decrease the expression level of
      HIF-1alpha in breast cancer cells MDA-MB-231 under hypoxia. The features of these
      analogues suggest their potential in cancer therapy.

PMID- 19111465
TI  - Synthesis and activity evaluation of benzoylurea derivatives as potential
      antiproliferative agents.
AB  - 3-Haloacylamino benzoylureas (3-HBUs) consist of a new family of tubulin ligands
      that kill cancer cells through mitotic arrest. In exploring the structure
      activity relationship (SAR), 17 analogues defined through variations of
      formylurea at the 1-position of the aromatic ring were synthesized. SAR analysis
      revealed that (i) the p-pi conjugation between the aromatic ring and formylurea
      was essential; (ii) suitable aryl substitutions at the N'-end increased
      anticancer activity with a mechanism different from that of parent compounds; and
      (iii) introduction of pyridyl at the N'-end provided an opportunity of making
      soluble salts to improve bioavailability. Among the analogues, 16c bearing 3,4,5
      trimethoxyphenyl and 16g bearing 2-pyridyl at the N'-end showed an enhanced
      activity and were active in hepatoma cells that were resistant to tubulin ligands
      including the parent compounds. Furthermore, 16c and 16g killed cancer cells with
      a mechanism independent of mitotic arrest, indicating a change of action mode.

PMID- 19111466
TI  - Novel HDAC6 isoform selective chiral small molecule histone deacetylase
      inhibitors.
AB  - In an effort to identify HDAC isoform selective inhibitors, we designed and
      synthesized novel, chiral 3,4-dihydroquinoxalin-2(1H)-one and piperazine-2,5
      dione aryl hydroxamates showing selectivity (up to 40-fold) for human HDAC6 over
      other class I/IIa HDACs. The observed selectivity and potency (IC(50) values 10
      200 nM against HDAC6) is markedly dependent on the absolute configuration of the
      chiral moiety, and suggests new possibilities for use of chiral compounds in
      selective HDAC isoform inhibition.

PMID- 19111467
TI  - A portable system for in-situ re-calibration of force platforms: experimental
      validation.
AB  - A system for the in-situ re-calibration of six-component force platforms is
      presented. The system consists of a device, a data-acquisition procedure and an
      algorithm. The device, simple and lightweight, is composed of a high-precision, 3
      D load cell, loaded through a triangular stage, and precisely positioned on the
      force platform under re-calibration by means of a template. The data-acquisition
      procedure lasts about 1h and requires up to 13 measurements consisting of manual
      positioning the load cell on the force platform, and then having the operator
      exerting loads on both load cell and force platform by his/her body movement. As
      a result, the procedure makes use of loads in the same range of posture and gait
      tests. The algorithm estimates the local or global six-by-six re-calibration
      matrix of the force platform through a least-squares optimization, and is
      presented in detail in a separate paper [Cedraro A, Cappello A, Chiari L. A
      portable system for in-situ re-calibration of force platforms: Theoretical
      validation. Gait Posture 2008;28:488-94]. The system was validated on four
      commercial force platforms (Amti OR6, Bertec 4060-08, Bertec 4080-10, and Kistler
      9286A). The average accuracy in the measurement of the center of pressure were
      2.3+/-1.4mm, 2.6+/-1.5mm, 11.8+/-4.3mm, 14.0+/-2.5mm before re-calibration, 1.1+/
      0.6mm, 1.8+/-1.1mm, 1.0+/-0.6mm, 3.2+/-1.1mm after global re-calibration, and
      0.7+/-0.4mm, 0.8+/-0.5mm, 0.5+/-0.3mm, 2.0+/-1.2mm after local re-calibration
      (results presented in random order). The force platform re-calibration influenced
      the value, sign, and timing of net joint moments, estimated during a gait task
      through an inverse dynamics approach.

PMID- 19111468
TI  - The dynamic balance of the children with cerebral palsy and typical developing
      during gait Part II: Instantaneous velocity and acceleration of COM and COP and
      their relationship.
AB  - As a companion research subsequent to analyzing displacement of center of mass
      (COM) and center of pressure (COP) in Part I, the purposes of this study were to
      quantify dynamic stability using magnitudes and patterns of instantaneous
      velocity and acceleration of COM and COP of the children with cerebral palsy (CP)
      during walking, and compare the data with those of the typically developing (TD)
      children. The instantaneous velocity and acceleration of COM and COP were
      acquired by calculating the first and second derivatives of displacement data
      presented in Part I. Velocity and acceleration of COM and COP were normalized by
      each participant's leg length to eliminate the influence of individual's stature.
      The results indicate that the preferred walking speed is significantly higher in
      TD groups than hemiplegic group (Hemi) and diplegic group (Di). The peak values
      of instantaneous velocity and acceleration of COM in vertical, medio-lateral (ML)
      and antero-posterior (AP) directions and velocity and acceleration of COP in ML
      direction were significantly higher in Di group than TD group. Both CP groups
      showed great variability in COM and COP parameters. Therefore, although Di group
      demonstrated higher peak values than Hemi group, the only significant difference
      between two groups was instantaneous COP velocity in ML direction. The findings
      of this study suggest that this assessment may be of value for research or
      clinical evaluation of dynamic balance dysfunction during walking and provide
      comparisons and insights for specific treatments or surgical interventions for
      the children with CP.

PMID- 19111469
TI  - The dynamic balance of the children with cerebral palsy and typical developing
      during gait. Part I: Spatial relationship between COM and COP trajectories.
AB  - Analysis of the COM or COP movement has been a simplified method to illustrate
      the balance disorders in static stance and gait, but has its limitation when
      examined alone. Dynamic stability of 32 children with cerebral palsy (CP) was
      examined and compared with 10 typically developing (TD) children by measuring the
      displacement of center of mass (COM) and center of pressure (COP) and their
      spatial relationship. The children with CP were further divided into two groups
      based on topographical involvement, hemiplegia (Hemi) and diplegia (Di). The
      participants walked with their preferred speed at least 5 successful trials on a
      walkway with two force plates mounted in the middle. An eight-camera motion
      analysis was used to capture 26 reflective markers secured at the bony landmarks
      of the participant. The data obtained from motion analysis and force plates was
      used to calculate COM and COP. The results showed either of two CP groups
      demonstrated significantly greater peak-to-peak COM and COP displacement in medio
      lateral (ML) and lower peak-to-peak COM and COP displacement in anterio-posterior
      (AP) direction than TD group. The root mean square (RMS) of COM-COP divergence of
      Hemi and Di groups were higher than that of TD group in AP and ML direction, but
      only the difference in ML direction was significant. Present study demonstrates
      that COM-COP divergence can characterize the dynamic balance of the CP children
      in walking, and thus assist in comparing and differentiating balance patterns.

PMID- 19111470
TI  - Clinical measurement of mobility and balance impairments in Huntington's disease:
      validity and responsiveness.
AB  - BACKGROUND: Mobility and balance in Huntington's disease (HD) are currently
      assessed in the clinic with three items from the unified Huntington's disease
      rating scale (UHDRS): walk, tandem and pull tests. These tests may not be optimal
      because they are scored on an ordinal scale and do not test anticipatory balance.
      We tested the validity and responsiveness of three clinical tests of mobility and
      balance. METHODS: Three clinical tests (FRT, timed up and go (TUG), Berg balance
      scale (BBS)) were validated with seven quantitative gait measures and two
      indicators of functional limitation (HD-ADL and total functional capacity) in 30
      subjects with HD. These tests were also assessed for responsiveness to disease
      severity. RESULTS: FRT and BBS were correlated with five quantitative gait
      measures, and TUG with eight (all p<0.05). All tests were correlated with
      indicators of functional limitation (p<0.05) and were responsive to disease
      severity. CONCLUSIONS: FRT, TUG and BBS are valid, responsive and easy to
      administer clinical tests that should be routinely included with the UHDRS in
      therapeutic trials for subjects with HD.

PMID- 19111471
TI  - Inhibition of the PCAF histone acetyl transferase and cell proliferation by
      isothiazolones.
AB  - Small molecule HAT inhibitors are useful tools to unravel the role of histone
      acetyl transferases (HATs) in the cell and have relevance for oncology. We
      present a systematic investigation of the inhibition of the HAT p300/CBP
      Associated Factor (PCAF) by isothiazolones with different substitutions. 5
      chloroisothiazolones proved to be the most potent inhibitors of PCAF. The growth
      inhibition of 4 different cell lines was studied and the growth of two cell lines
      (A2780 and HEK 293) was inhibited at micromolar concentrations by 5
      chloroisothiazolones. Furthermore, the 5-chloroisothiazolone preservative Kathon
      CG that is used in cosmetics inhibited PCAF and the growth of cell lines A2780
      and HEK 293, which indicates that this preservative should be applied with care.

PMID- 19111472
TI  - Radionuclide impurities in proton-irradiated [18O]H2O for the production of 18F-:
      activities and distribution in the [18F]FDG synthesis process.
AB  - Proton- and neutron-induced activation products in the components of a high
      pressure [(18)O]H(2)O target vessel used for the production of (18)F(-) in a
      medical cyclotron have been identified using high resolution gamma spectrometry.
      The activities leached from the target vessel into the [(18)O]H(2)O during
      irradiation, and the distribution of the identified radionuclide impurities in
      the various cartridges and solutions used in the [(18)F]FDG synthesis process
      have been measured and are discussed from the perspective of waste disposal. The
      results indicate that, at the energies and beam currents employed, only a few,
      relatively short-lived radionuclides are present in the irradiated [(18)O]H(2)O,
      and that the activities involved (<10 kBq in each case) are well below typical
      exemption limits. Activities of beta-emitting (3)H in irradiated [(18)O]H(2)O,
      produced via the (18)O(p,(3)H)(16)O reaction, have also been determined using
      liquid scintillation spectrometry. Measured activity concentrations, in the range
      150-180 kBq g(-1), are consistent with those reported by other workers. Analyses
      of the synthesised [(18)F]FDG confirm the radiochemical purity of the product,
      both for (3)H and for gamma-emitting radionuclides in the energy range 25-1650
      keV.

PMID- 19111473
TI  - Elderly patients with advanced colorectal cancer derive similar benefit without
      excessive toxicity after first-line chemotherapy with oxaliplatin-based
      combinations: comparative outcomes from the 03-TTD-01 phase III study.
AB  - PURPOSE: Healthy elderly patients with metastatic colorectal cancer may benefit
      from chemotherapy as much as the younger population. This analysis compares the
      outcomes of first-line oxaliplatin plus fluoropyrimidines in elderly versus young
      patients. PATIENTS AND METHODS: 348 patients were randomized to capecitabine 1000
      mg/(m2 12 h), days 1-14 plus oxaliplatin 130 mg/m2 day 1, every 3 weeks or weekly
      infusional 5-FU 2250 mg/m2 over 48 h plus bimonthly oxaliplatin 85 mg/m2. We
      evaluated response rate, time to progression, overall survival and toxicity
      according to age. RESULTS: ORR for elderly and young patients were 34.9% and
      44.7%, respectively (p=0.081). Median TTP did not differ between the two groups:
      8.3 months for patients > or =70 years and 9.6 months for those <70 years
      (p=0.114). Median OS was 16.8 months and 20.5 months for the > or =70 and <70
      years groups, respectively (p=0.74). With XELOX, mild paresthesia and an increase
      in transaminase levels were more frequent for young patients, whereas grade 3/4
      diarrhea was higher in those > or =70 years (25% vs. 8%, p=0.005). For FUOX, only
      paresthesia was significantly lower in patients > or =70 years (53% vs. 71%,
      p=0.032). CONCLUSION: Elderly patients with MCRC benefit from first-line
      oxaliplatin-fluoropyrimidine combinations as much as younger patients, without
      increased toxicity.

PMID- 19111474
TI  - Pharmacologic rationale for early G-CSF prophylaxis in cancer patients and role
      of pharmacogenetics in treatment optimization.
AB  - The use of recombinant human granulocyte colony stimulating factors (G-CSF) has
      become an integral part of supportive care during cytotoxic chemotherapy. Current
      guidelines recommend the use of G-CSF in patients with substantial risk of
      febrile neutropenia. However, little consensus exists about optimal timing and
      tailoring of this therapy. Based on the known effects of chemotherapy and G-CSF
      on bone marrow compartments, we propose a model that supports the prophylactic
      rather than therapeutic use of G-CSF therapy. In addition, several genetic
      alterations in G-CSF signalling pathway have been described. These genetic
      variants may predict the risk of febrile neutropenia and response to G-CSF. Thus,
      future pharmacogenetic/omics studies in this field are warranted. Through the
      identification of patients at risk and the knowledge of biological basis for
      optimal timing, hopefully we should soon be able to improve the application of
      the existing guidelines for G-CSF therapy and patient's prognosis.

PMID- 19111475
TI  - Relative contribution of acromioclavicular joint capsule and coracoclavicular
      ligaments to acromioclavicular stability.
AB  - HYPOTHESIS: We hypothesized that both the AC joint capsule and CC ligaments are
      biomechanically robust structures in the anterior-posterior (AP) and superior
      inferior (SI) planes with low loads, and that these ligaments provide essential
      function in AC joint stability. MATERIALS AND METHODS: Anterior-posterior (AP)
      and superior-inferior (SI) AC joint translations were quantified in 6 cadaver
      matched pairs with AC joint compressions of 10N, 20N and 30N, and with
      translational loads of 10N and 15N. Either the AC joint capsule or CC ligaments
      were transected, and measurements were then repeated. Biomechanical
      characteristics of the remaining AC joint capsule or CC ligaments were compared.
      RESULTS: There were significant increases in AP translation with the cut AC joint
      capsule, and significant increases in SI translation with the cut CC ligaments (P
      < 0.0001). Compression significantly decreased translation (P < 0.0001).
      DISCUSSION: Our study is supported by, and further develops, recent studies and
      anatomical knowledge. It offers two interpreted pieces of information for the
      sports medicine physician to consider for reconstruction of the AC joint. First,
      resection of the distal clavicle may have a detrimental effect. Second, repair of
      the AC joint capsule, in addition to the customarily repaired CC ligaments,
      appears to have a beneficial effect. CONCLUSION: The AC joint capsule is a robust
      anatomical structure that contributes significantly to the AC joint stability,
      especially in the AP plane. Compression increases stability. LEVEL OF EVIDENCE:
      Basic science study.

PMID- 19111476
TI  - Reconstruction plates for stabilization of mid-shaft clavicle fractures:
      differences between nonlocked and locked plates in two different positions.
AB  - Reconstruction plates permit contouring to the irregular anatomic shape of the
      clavicle. This study evaluated the biomechanical stability of locking and
      nonlocking clavicle reconstruction plates for treating midshaft, transverse
      fractures, comparing anterior-inferior to superior plate position. Twenty-four
      synthetic clavicles with mid-shaft fractures were repaired with either a locking
      or nonlocking clavicle reconstruction plate in either the anterior-inferior or
      superior plate position (n = 6/group). Repaired constructs were tested in axial
      compression, axial torsion, and cantilever bending failure. In compression,
      anterior-inferior plates were significantly stiffer than superior plates and
      locked plates stiffer than nonlocked. In torsion, anterior-inferior plates were
      stiffer, with a significant interaction term that favored anterior-inferior
      locked and superior nonlocked plates. In cantilever bending, superior plates had
      a significantly higher bending failure load and stiffness. Anterior-inferior
      plates failed at a significantly lower load ( approximately 40 N or approximately
      4 kg), which could potentially occur in the postoperative period.

PMID- 19111477
TI  - Shoulder evaluation with isokinetic strength testing after arthroscopic rotator
      cuff repairs.
AB  - HYPOTHESIS: The purpose of this study was to evaluate, with isokinetic testing,
      the recovery of strength in patients with rotator cuff tears treated with two
      different arthroscopic repair techniques. MATERIALS AND METHODS: From September
      2004 to September 2006, patients with a full-thickness supraspinatus tear were
      randomized to two different groups. Patients in group 1 underwent side-to-side
      repair with permanent sutures, whereas those in group 2 underwent tendon-to-bone
      fixation with 1 metal suture anchor loaded with double sutures. The same
      independent examiner evaluated the outcomes using the Constant score and
      isokinetic strength testing preoperatively and at 3, 6, and 12 months
      postoperatively. Data analysis was also performed in three subgroups: small,
      medium, and large tears. RESULTS: Constant scores improved from preoperatively to
      12 months postoperatively. In group 1, the mean Constant score was 32 points
      before surgery and 78 points at 12 months postoperatively. In group 2, the mean
      Constant score was 30 points before surgery and 88 points at 12 months after
      surgery. Strength increased gradually during the first postoperative year. In
      group 1, preoperative mean peak torque was 34% and 39% in internal rotation and
      external rotation, respectively. After repair, it decreased to 17% and 21%,
      respectively, at 12 months. In group 2, preoperative mean peak torque was 32% and
      37% in internal rotation and external rotation, respectively; after surgery, it
      decreased to 9% and 12%, respectively, at 12 months. Data analysis showed that
      the difference in improvement in Constant scores and in strength recovery from
      preoperatively to postoperatively in groups 1 and 2 was statistically significant
      (p < .05). CONCLUSION: We showed a strength difference between patients with side
      to-side repairs and those with tendon-to-bone repairs. LEVEL OF EVIDENCE: Level
      1; Prospective randomized study.

PMID- 19111478
TI  - Myocardial infarction following convulsive and nonconvulsive seizures.
AB  - Myocardial infarction (MI) has been rarely reported in association with seizures,
      and only of convulsive type. METHODS: We describe a series of five patients
      observed over a 4-year period, who presented MI immediately following seizures,
      either convulsive or nonconvulsive. RESULTS: Patient 1 had pre-existent coronary
      disease (CD) and presented multiple focal nonconvulsive seizures. Patient 2 had
      no CD, normal coronary angiography and presented secondary generalized convulsive
      seizures. Patient 3 had no history of CD, normal angiography and had a first
      single convulsive seizure. Patient 4 had severe CD and suffered from a single
      convulsive event. Patient 5 had a partial and a generalized seizure and had no
      known CD. CONCLUSIONS: MI following seizures is not an exceptional event and can
      occur in a spectrum of conditions including single or repeated, convulsive or
      nonconvulsive seizures, in patients with or without pre-existing coronary
      disease. We suggest that the occurrence of MI should be considered in epileptic
      patients during and shortly after seizures.

PMID- 19111479
TI  - Prosthetic carotid bypass grafts for atherosclerotic lesions: a prospective study
      of 198 consecutive cases.
AB  - OBJECTIVES: Carotid endarterectomy (CEA) is the standard treatment for
      atherosclerotic lesions involving the carotid bifurcation. However, CEA can be
      challenging under some conditions. The goal of this study was to determine the
      outcome and durability of prosthetic carotid bypass grafting (PCB) with
      polytetrafluoroethylene (PTFE) grafts as an alternative to CEA. METHODS: This is
      a prospective series of 198 consecutive patients with PCB, representing 12.4% of
      1595 patients with a carotid reconstruction procedure performed in our department
      between September 1986 and December 2006. Qualifying event was stroke in 67
      patients (34%) and transient ischaemic attack (TIA) in 45 (23%), and 86 patients
      (43%) were asymptomatic. Primary indications for PCB were extensive
      atherosclerotic lesions (n=71; 36%), carotid stenosis associated with kinking
      (n=49; 25%), recurrent stenosis (n=47; 23%), stenosis after radiation therapy
      (n=18; 9%) and technical failure of CEA (n=13; 7%), with excessive arterial wall
      thinning and perforation after endarterectomy (n=10) or intimal flap on
      completion digital angiography (n=3). RESULTS: The combined stroke and death rate
      at 30 days were 0.5% (one stroke). Median follow-up was 9.5 years (interquartile
      range (IQR): 6.2-18.3 years). At 10 years, primary patency was 97.9+/-3.4%. Six
      PCBs (3.0%) became occluded during follow-up; one patient had a restenosis
      greater than 50% and 18 patients (9.1%) had a restenosis of less than 50%. Five
      patients had an ipsilateral stroke (one postoperative stroke, one at 103 days
      with a patent PCB and three related to occlusion of the PCB at 4, 13 and 15 years
      after the procedure). At 10 years, cumulative stroke-free survival was 98.4+/
      3.2%, and cumulative survival was 78.8+/-7.0%. CONCLUSIONS: PCB is a safe
      surgical alternative and is durable, with a low incidence of graft restenosis,
      when CEA seems hazardous.

PMID- 19111480
TI  - Perioperative red blood cell transfusion and outcome in stable patients after
      elective major vascular surgery.
AB  - OBJECTIVES: Definitive evidence that red blood cell transfusion improves outcome
      after vascular surgery is lacking. The aims of the study were to determine, among
      stable consecutive patients who underwent elective major vascular surgery, (1)
      the association between postoperative transfusion and 30-day death, myocardial
      infarction, and both, and (2) and if this association differs according to the
      presence of postoperative anaemia (haemoglobin value less than 9.0 g/dL within 7
      days after surgery). METHODS: A retrospective observational study was conducted
      on 359 patients prospectively screened according to the ACC/AHA guidelines for
      preoperative risk in non-cardiac surgery. Main outcome was 30-day death;
      secondary outcomes 30-day myocardial infarction, and composite of 30-day
      myocardial infarction or death. RESULTS: Of the patients included, 95 (26.5%)
      received at least one unit of red blood cells. Patients who received transfusion
      had a significantly increased hazard of 30-day death (hazard ratio [HR] 11.72,
      95% confidence interval [CI] 3.92-35.10; p<0.0001), myocardial infarction (HR
      3.3, 95% CI 1.7-6.1; p=0.0003), and both (HR 4.0 95% CI 2.2-7.3; p<0.0001). Such
      associations held even after adjusting for baseline characteristics, surgical
      risk, bleeding, and propensity to receive transfusion. There was a significant
      interaction between transfusion and postoperative anaemia (p=0.012). In patients
      without anaemia, transfusion was associated with higher risk of 30-day death (HR
      19.20, 95% CI 3.99-92.45; p=0.007), myocardial infarction (HR 5.05, 95% CI 2.23
      11.44; p=0.0001), and both. Conversely, in patients with anaemia this association
      was not significant. CONCLUSIONS: In patients who underwent elective major
      vascular surgery, perioperative transfusion was associated with a significantly
      increased risk of 30-day events which was more attributable to patients with
      lesser degree of anaemia. Our data caution against the use of liberal transfusion
      in stable vascular surgery patients.

PMID- 19111481
TI  - Whole genome-expression profiling reveals a role for immune and inflammatory
      response in abdominal aortic aneurysm rupture.
AB  - OBJECTIVES: This study used the whole transcriptome approach to investigate the
      role of genes involved in immune and inflammatory response at the site of
      aneurysm rupture. MATERIALS AND METHODS: Rupture site and paired anterior sac
      biopsies (internal control) of ruptured abdominal aortic aneurysms (AAAs) (n=10)
      were analysed with Affymetrix Human Genome U133A plus 2.0 microarray. Twenty-one
      differentially expressed genes were selected for validation using quantitative
      reverse transcriptase polymerase chain reaction (QRT-PCR). RESULTS: A total of
      139 genes (123 upregulated, 16 downregulated) at the aneurysm rupture site were
      differentially expressed (>2.5-fold, P<0.005). Immune and inflammatory responses
      (Gene Ontology Classification) were frequently associated with the differentially
      expressed genes. Genes with immune and inflammatory functions that were
      confirmed, by QRT-PCR, to be overexpressed at the aneurysm rupture site were
      interleukins-6 and -8 (IL-6 and -8), Selectin E (SELE), prostaglandin
      endoperoxidase synthase 2 (COX2) and prokineticin 2 (PROK2). IL-6 (pro-immune)
      and IL-8 (pro-immune and pro-inflammatory) have previously been linked to
      aneurysm rupture; and SELE and COX2 (pro-inflammatory) have previous associations
      with aneurysm development but not rupture. CONCLUSIONS: The differential
      expression of genes involved in immune and inflammatory responses was confirmed
      at AAA rupture site. These genes may represent novel targets for treatment of
      aneurysms.

PMID- 19111482
TI  - Search for serum biomarkers associated with abdominal aortic aneurysm growth--a
      pilot study.
AB  - INTRODUCTION: Serological biomarkers could reflect asymptomatic infrarenal aortic
      aneurysm (AAA) activity and guide patient management. REPORT: Serum
      concentrations of C-reactive protein (CRP), alpha 1-antitrypsin and
      lipoprotein(a) were measured in blood samples from 35 AAA patients and 35
      controls and correlated with the aortic diameter and AAA growth in the previous
      12 months. We found a positive correlation between CRP and AAA diameter (r=0.46;
      p=0.007) and alpha 1-antitrypsin and AAA growth (r=0.55; p=0.004). CONCLUSIONS:
      Alpha 1-antitrypsin may be a promising biomarker of AAA growth.

PMID- 19111483
TI  - Comment on "Clinical endpoints in peripheral endovascular revascularisation
      trials: a case for standardised definitions Eur J Vasc Endovasc Surg 2008;36:409
      9".

PMID- 19111484
TI  - Popliteal vein compression under general anaesthesia.
AB  - OBJECTIVES: To determine the incidence of popliteal vein compression in supine
      patients, who are under general anaesthesia and using heel elevators. DESIGN: A
      prospective cohort study. METHODS: The popliteal veins of 50 patients, lying
      supine under general anaesthesia, were insonated using duplex ultrasonography to
      determine the incidence of popliteal vein compression when the knees were flexed
      and extended. RESULT: There was a statistically significant reduction in
      popliteal vein diameter in extension compared with the diameter in flexion
      (median diameter: flexed 7.6mm, extended 2.1mm, p<0.001, Wilcoxon test). In
      extension, 43% of veins occluded, and a further 21% was compressed by >or=50%.
      There was a significant relationship to body mass index (BMI) but not to height,
      gender or age; all patients with BMI >or=30 displayed narrowing at least one vein
      by >or=50%. The relative risk of vein narrowing >or=50% or occlusion was 1.55 for
      BMI >or=25 versus <25, and 1.67 for BMI >or=30 versus <25. CONCLUSION: Knee
      hyperextension in supine patients during general anaesthesia leads to popliteal
      vein compression or occlusion. The likelihood of compression increases with
      higher BMIs.

PMID- 19111485
TI  - Randomised comparison of costs and cost-effectiveness of cryostripping and
      endovenous laser ablation for varicose veins: 2-year results.
AB  - BACKGROUND: Although endovenous laser ablation for varicose veins is replacing
      surgical stripping, proper economic evaluation with adequate follow-up in a
      randomised clinical trial is important for considered policy decisions regarding
      the implementation of new techniques. METHODS: Data from a randomised controlled
      trial comparing cryostripping and endovenous laser ablation in 120 patients were
      combined to study Short Form (SF) 6D outcome, costs and cost-effectiveness 2
      years after treatment. Incremental cost per quality-adjusted life year (QALY)
      gained 2 years after treatment was calculated using different strategies, and
      uncertainty was assessed with bootstrapping. RESULTS: Over the total study
      period, mean SF-6D scores improved slightly from 0.78 at baseline to 0.80 at 2
      years for patients who underwent cryostripping and from 0.77 to 0.79 for patients
      who underwent endovenous laser. QALY (SF-6D) was 1.59 in patients who underwent
      cryostripping and 1.60 in patients who underwent endovenous laser 2 years after
      treatment. The costs of cryostripping and endovenous laser per patient were euro
      2651 and euro 2783, respectively. Bootstrapping indicated that cryostripping was
      associated with an incremental cost-effectiveness ratio of euro 32 per QALY
      gained. With regard to different strategies, outpatient cryostripping was less
      costly and more effective 2 years after treatment. CONCLUSION: In this study, in
      terms of costs per QALY gained, outpatient cryostripping appeared to be the
      dominant strategy, but endovenous laser yielded comparable outcomes for a
      relatively little additional cost.

PMID- 19111486
TI  - A case of facial myofascial pain syndrome presenting as trigeminal neuralgia.
AB  - Facial pain has many causes, including idiopathic factors, trigeminal neuralgia,
      dental problems, temporomandibular joint disorders, cranial abnormalities, and
      infections. However, the clinical diagnosis of facial pain is sometimes difficult
      to establish because clinical manifestations commonly overlap. The diagnosis of
      trigeminal neuralgia is based solely on clinical findings. Therefore, a careful
      evaluation of the patient history and a thorough physical examination are
      essential. This case describes a patient with facial myofascial pain syndrome
      involving the right zygomaticus, orbicularis oculi, and levator labii muscles,
      which presented as trigeminal neuralgia.

PMID- 19111487
TI  - Contribution of individual, workplace, psychosocial and physiological factors to
      neck pain in female office workers.
AB  - This study investigated the relative contribution of individual, workplace,
      psychosocial and physiological features associated with neck pain in female
      office workers towards developing appropriate intervention programs. Workers
      without disability (Neck Disability Index (NDI) score < or = 8, n=33); workers
      with neck pain and disability (NDI > or = 9/100, n=52) and 22 controls (women who
      did not work and without neck pain) participated in this study. Two logistic
      regression models were constructed to test the association between various
      measures in (1) workers with and without disability, and (2) workers without
      disability and controls. Measures included those found to be significantly
      associated with higher NDI in our previous studies: psychosocial domains;
      individual factors; task demands; quantitative sensory measures and measures of
      motor function. In the final model, higher score on negative affectivity scale
      (OR=4.47), greater activity in the neck flexors during cranio-cervical flexion
      (OR=1.44), cold hyperalgesia (OR=1.27) and longer duration of symptoms (OR=1.19)
      remained significantly associated with neck pain in workers. Workers without
      disability and controls could only be differentiated by greater muscle activity
      in the cervical flexors and extensors during a typing task. No psychosocial
      domains remained in either regression model. These results suggest that
      impairments in the sensory and motor system should be considered in any
      assessment of the office worker with neck pain and may have stronger influences
      on the presenting symptoms than workplace and psychosocial features.

PMID- 19111488
TI  - Homology modeling of human transketolase: description of critical sites useful
      for drug design and study of the cofactor binding mode.
AB  - Transketolase, the most critical enzyme of the non-oxidative branch of the
      pentose phosphate pathway, has been reported as a new target protein for cancer
      research. However, since the crystal structure of human Transketolase is unknown,
      no structure-based methods can be used to identify new inhibitors. We performed
      homology modeling of human Transketolase using the crystal structure of yeast as
      a template, and then refined the model through molecular dynamics simulations.
      Based on the resulting structure we propose five critical sites containing
      arginines (Arg 101, Arg 318, Arg 395, Arg 401 and Arg 474) that contribute to
      dimer stability or catalytic activity. In addition, an interaction analysis of
      its cofactor (thiamine pyrophosphate) and a binding site description were carried
      out, suggesting the substrate channel already identified in yeast Transketolase.
      A binding free energy calculation of its cofactor was performed to establish the
      main driving forces of binding. In summary, we describe a reliable model of human
      Transketolase that can be used in structure-based drug design and in the search
      for new Transketolase inhibitors that disrupt dimer stability and cover the
      critical sites found.

PMID- 19111489
TI  - Dual-energy X-ray absorptiometry assessment of tibial mid-third bone mineral
      density in young athletes.
AB  - We suggested a new reproducible method to measure densitometric values at mid
      third part of the tibia by dual-energy X-ray absorptiometry (DXA; Delphi,
      Hologic, Waltham, MA) in a population of young adults. Our population was
      composed of 170 subjects aged 22.7+/-4.0 yr: athlete men (n=67) and women (n=40);
      control men (n=33) and women (n=30). Athletes practiced collective sports, judo
      or weightlifting for 10.0+/-3.6 h/wk. We measured bone area (cm2), bone mineral
      content (BMC, g), and bone mineral density (BMD, g/cm2) at the left total hip and
      the mid-third part of the tibia with DXA. For the tibia scan, we used the whole
      body mode. To ensure the reproducibility of the method, both legs were extended
      and the feet were maintained on a support in an internal rotation of 35 degrees.
      The region of interest of the lumbar spine from the whole body scan was
      positioned around the mid-third part of the tibia. Area, BMC, and BMD values were
      significantly higher in athletes compared with those of controls. The intra- and
      interobserver variability of the image analysis were 0.38% and 1.01%,
      respectively. For BMD measurements, the short-term (4 scans/d) and mid-term (4
      scans/mo) reproducibility were 1.33% and 1.94%, respectively. DXA is a suitable
      tool to evaluate densitometric measurements at the mid-third part of the tibia
      and the influence of physical activity on that bone site.

PMID- 19111490
TI  - Growth hormone/insulin-like growth factor axis in patients with subclinical
      thyroid dysfunction.
AB  - OBJECTIVE: Our aim was to evaluate serum concentrations of GH, IGF-I, and insulin
      like growth factor-binding protein-3 (IGFBP-3) in patients with subclinical
      thyroid dysfunction before and after normalization of thyroid function. DESIGN
      AND METHODS: The study included 51 patients (mean age 42.2+/-1.8 years) with
      subclinical hypothyroidism and 30 patients (mean age 44.3+/-2.4 years) with
      subclinical hyperthyroidism. A group of 37 euthyroid healthy subjects were
      studied as controls. Serum concentrations of TSH, FT4, FT3, GH, insulin, IGF-I,
      and IGFBP-3 were measured in all patients before starting therapy and after
      normalization of thyroid function. The dosage of levothyroxine (LT4) and
      antithyroid drugs was adjusted in attempt to keep the serum-free thyroxine (FT4)
      and thyrotropin (TSH) concentrations within the normal range. MAIN OUTCOME:
      Baseline growth hormone levels were similar with hypothyroid group and
      hyperthyroid group in relation to euthyroid control subjects. Fasting serum IGF-I
      levels were significantly lower in the subclinical hypothyroid group compared
      with the control group. On the other hand, IGF-I levels of subclinical
      hyperthyroid patients and control group were similar. After normalization of
      thyroid function tests, IGF-I concentrations were increased in subclinical
      hypothyroid subjects, but unchanged in subclinical hyperthyroid subjects.
      Patients with subclinical hyperthyroidism showed slightly lower mean serum IGFBP
      3 concentrations than those found in control group, but the difference was not
      statistically significant. Serum GH and IGFBP-3 levels were unaltered by
      treatment. CONCLUSIONS: In this study, it was shown that GH-IGF axis was not
      affected in patients with subclinical hyperthyroidism, while it was affected in
      patients with subclinical hypothyroidism. That is, investigation of the axis in
      subclinical hyperthyroidism would not bring any extra advantages, but LT4
      replacement therapy could prevent abnormalities related to GH-IGF axis in
      patients with subclinical hypothyroidism.

PMID- 19111491
TI  - Condition-based use of antimicrobials in cats in Finland: results from two
      surveys.
AB  - Two surveys were carried out to investigate how antimicrobials are used in cats
      in Finland. Information was retrieved from 419 prescriptions and 311
      questionnaire sheets concerning antimicrobial treatment for feline patients.
      Infected wounds, skin disorders and urinary tract infections were the most common
      reasons for antimicrobial treatment in cats. Compliance with prudent use
      guidelines was good. beta-Lactams such as amoxycillin and amoxycillin with
      clavulanic acid were frequently used. Fluoroquinolones were used judiciously. The
      median length of treatment was 10 days for most conditions. Diagnosis was mainly
      based on clinical signs, and bacteriological culture and sensitivity testing was
      rarely performed. This study provides basic descriptive information on how
      antimicrobials are used in cats and that could help when revising guidelines for
      the condition-based use of antimicrobials in animals.

PMID- 19111492
TI  - Modified temporal approach for a rostro-temporal basal meningioma in a cat.
AB  - An 11-year-old neutered female domestic shorthair indoor cat was presented to our
      hospital for treatment of a left-sided rostro-temporal basal meningioma. Focal
      seizures in the facial muscles had been observed sporadically for 1 year. Two
      weeks prior to presentation the cat had developed generalised seizures and was
      treated with symptomatic anticonvulsive treatment. Focal facial seizures,
      especially on the right side, persisted after medical therapy. From the computed
      tomography scan, a basal meningioma was suspected by the treating veterinarian. A
      left-sided suprazygomatical temporobasal approach to the zygomatic arch was
      chosen because it causes less soft tissue damage. After craniotomy, durotomy and
      gentle dorsal retraction of the left piriform lobe, the meningioma was removed.
      Postoperative magnetic resonance imaging confirmed complete excision of the
      tumour. One day after surgery the cat was alert and a left-sided facial nerve
      palsy was noticed. Otherwise the neurological examination was normal.
      Anticonvulsive and eye moistening therapy was continued for 3 months. Six months
      after surgery the cat was clinically normal without any recurrence of seizures.

PMID- 19111493
TI  - Primary drug resistance in antiretroviral-naive injection drug users.
AB  - OBJECTIVES: We evaluated the prevalence of primary HIV drug resistance in a
      population of 128 injection drug users (48 female) prior to initiating
      antiretroviral therapy. METHODS: Genotypic and phenotypic profiles were obtained
      retrospectively for the period June 1996 to February 2007. Genotypic drug
      resistance was defined as the presence of a major mutation (IAS-USA table, 2007
      revision), adding revertants at reverse transcriptase (RT) codon 215. Phenotypic
      drug resistance was defined as the fold change associated with >or=80% loss of
      the wild type virologic response due to viral resistance based on virtual
      phenotype analysis. RESULTS: Genotypic drug resistance was uncommon, and was only
      identified in six (4.7%) cases, all in the RT gene (L100I, K103N, Y181C, M184V,
      Y188L, and T215D). There were no cases of multi-class or protease inhibitor (PI)
      resistance. However, polymorphisms in the protease and RT genes were extremely
      common. Phenotypic drug resistance was also identified in six (4.7%) patients,
      four in the RT gene (in patients with mutations K103N, Y181C, M184V and Y188L)
      and two the protease gene (in two patients with minor PI mutations). In addition,
      25 (19.5%) of the patients had reduced susceptibility to PIs, defined as
      resistance>20% but <80% of the wild type virologic response, with no primary PI
      mutations detected in all these patients. CONCLUSION: The prevalence of primary
      HIV drug resistance was low in this population of injection drug users.

PMID- 19111494
TI  - Influenza-associated morbidity in subtropical Taiwan.
AB  - OBJECTIVES: The purpose of this study was to assess the characteristics of
      influenza-associated morbidity in subtropical Taiwan, corresponding to the
      seasonal patterns, weather, and co-circulation of influenza (sub)types, and other
      respiratory viruses, where the burden of influenza is poorly quantified. METHODS:
      This study applied the virus variation-guided Poisson seasonal regression models
      to evaluate the impact of epidemic influenza on morbidity in Taiwan for 1999
      2006. The models allow for the adjusting of influenza-associated morbidity for
      factors such as annual trend, seasonality, temperature, relative humidity,
      influenza A (H1N1), A (H3N2), B, and respiratory syncytial virus. RESULTS:
      Influenza-associated morbidity was associated more strongly with temperature than
      relative humidity. Influenza A (H3N2) was more coordinated with other virus
      (sub)types than A (H1N1). Type B dominated simultaneously with A (H3N2) at times,
      whereas A (H3N2) and A (H1N1) rarely dominated simultaneously with each other.
      Epidemiologically, A (H3N2) appeared to be the dominant subtype (51%), followed
      by type B (39%) and then A (H1N1) (10%) for influenza-associated morbidity.
      CONCLUSIONS: This study suggests that seasonality and influenza (sub)types
      contribute significantly to influenza morbidity in subtropical Taiwan. This is
      important for influenza control managers who are involved actively in using
      epidemic and climate information to achieve influenza-reduction targets in
      subtropical regions.

PMID- 19111496
TI  - [OG resident training in France: first stop: CHU of Tours].

PMID- 19111495
TI  - Gender differences in the clinical diagnosis of tuberculous lymphadenitis--a
      hospital-based study from Central India.
AB  - OBJECTIVE: Tuberculous lymphadenitis can be difficult to diagnose clinically, and
      as it is thought to be more common in females, we describe here the clinical
      characteristics of cervical tuberculous lymphadenitis in men and women and
      compare this with cytology to assess their diagnostic value. METHODS: Two hundred
      and nineteen patients with tuberculous lymphadenitis, aged 14 years or more, who
      presented with a neck mass to the Department of Pathology, Ujjain Hospital,
      Ujjain, India were included in the study. The presenting clinical symptoms and
      signs were compared between men and women and with the cytology of fine needle
      aspirates from the lymph nodes. RESULTS: Seventy-five percent of the patients
      were aged between 14 and 35 years, with a male to female ratio of 1:2.1. One or
      more constitutional symptoms were present in 56.6% of patients on presentation.
      There were more men with clinical symptoms than women. Fever was the most common
      manifestation in both gender groups. Fever for more than 30 days, cough, weight
      loss, and night sweats were significantly more common in men. On cytology,
      necrotic granulomas were found to be associated with constitutional symptoms.
      CONCLUSIONS: Constitutional symptoms were more frequently reported by men than by
      women and showed a correlation with necrotic granulomas on cytology.

PMID- 19111497
TI  - [Chi2 test for two by two percentage comparison table].

PMID- 19111498
TI  - Synthesis and characterization of a new metal-organic NLO material: dibromo
      bis(triphenylphosphine oxide) mercury(II).
AB  - A new metal-organic nonlinear optical dibromo bis(triphenylphosphine oxide)
      mercury(II) (HgBr(2)(TPPO)(2), TPPO=triphenylphosphine oxide) crystal has been
      synthesized. Single-crystal X-ray diffraction reveals that HgBr(2)(TPPO)(2)
      crystallizes in the orthorhombic system, space group Pna2(1), a=21.174A,
      b=9.1979A, c=17.468A, and Z=4. The crystal was also characterized by FTIR
      spectroscopy, differential scanning calorimetry (DSC), thermal gravity analysis
      (TGA), and UV-vis-IR spectroscopy. Thermal analyses confirmed that the crystal is
      stable up to 151 degrees C. The transmission spectrum of the crystal shows that
      the lower cut off wavelength lies at 340nm. The nonlinear optical (NLO) property
      of HgBr(2)(TPPO)(2) has been estimated by Kurtz-powder second harmonic generation
      (SHG) test.

PMID- 19111499
TI  - Raman spectroscopy as an effective tool for high-resolution heavy-mineral
      analysis: examples from major Himalayan and Alpine fluvio-deltaic systems.
AB  - Raman spectroscopy represents a new way to obtain detailed comprehensive
      information on heavy-mineral assemblages. In this work are presented several
      examples from major Alpine (Po River) and Himalayan (Ganga and Brahmaputra
      Rivers) fluvio-deltaic sands. Our attention was focused on the chemical
      properties of garnet, which is a widespread mineral in orogenic sediments, easy
      to be identified, and relatively stable during both equatorial weathering and
      intrastratal dissolution. Garnet grains were studied in different samples
      representative of various depositional environments (fluvial bar, fluvial levee,
      shoreface, beach berm, eolian dune), in order to investigate specifically the
      hydraulic behaviour of grains with different density in different hydrodynamic
      conditions. Raman spectra and semi-quantitative analysis of Raman shifts allowed
      us to rapidly determine the distribution of garnet types in each sample in order
      to obtain chemical composition, to calculate the density of each garnet, and
      finally to infer their respective provenance. This manuscript presents one
      possible application of the "MIRAGEM" method described by Bersani et al. in this
      volume. References, data sets and details on the analytical routine are widely
      explained in the above mentioned work.

PMID- 19111501
TI  - Microdetermination of proteins by resonance light scattering technique based on
      aggregation of ferric nanoparticles.
AB  - A new method for protein determination is presented that allows measurement of
      proteins at nanogram levels with simple procedure. The method applies a resonance
      light scattering (RLS) technique, but based on aggregation of ferric
      nanoparticles on protein template instead of the usual interaction of organic
      days with proteins. By mixing ferric colloid with sodium cacodylate buffer
      solution, ferric nanoparticles can be obtained in the size of about 5nm and kept
      their positive charges in a wide range of pH 1.8-7.6. The ferric nanoparticles
      can interact with proteins to form particular aggregates and thus result in
      strong and stable RLS. Under optimal conditions (wavelength of 451nm and pH 7.4),
      few substances interfere with this assay. The detection limitation of bovine
      serum albumin (BSA) is 6.6ng/mL and the linear range is 20-700ng/mL. This method
      gives almost identical responses for BSA, human serum albumin (HSA) and gamma
      globulin (gamma-G), and can be used for the determination of total proteins in
      human serum with satisfactory results.

PMID- 19111500
TI  - Spectroscopic properties and energy transfer of Tm(3+)/Ho(3+)-codoped TeO(2)
      WO(3)-ZnO glasses for 1.47mum amplifier.
AB  - We report on spectroscopic properties and energy transfer of Tm(3+)/Ho(3+)
      codoped tungsten tellurite glasses for 1.47microm amplifier. Fluorescence spectra
      and the analysis of energy transfer indicate that Ho(3+) is an excellent codopant
      for 1.47microm emission. Comparing with other tellurite glasses, the radiative
      lifetime of the (3)H(4) level of Tm(3+) in tungsten tellurite glass is slightly
      lower, but the spontaneous emission probability, stimulated emission cross
      section and the figure of merit for bandwidth are obviously larger. Although the
      pump efficiency of tungsten tellurite amplifier is approximately 50% less than
      that of fluoride glass, the figure of merit for bandwidth is approximately three
      times larger in tungsten tellurite glass than in fluoride glass. The results
      indicate that Tm(3+)/Ho(3+)-codoped tungsten tellurite glass is attractive for
      broadband amplifier.

PMID- 19111502
TI  - Q branch features in the hot parallel bands of (13)C(2)H(2) in the three micron
      region.
AB  - A systematic study of the high-resolution spectrum of (13)C(2)H(2) in the 3microm
      spectral region shows Q branch features in five hot parallel bands. These bands
      are due to the nu(3)+nu(4) (Pi(u))<--nu(4) (Pi(g)), nu(3)+nu(5) (Pi(g))<-
      nu(5)(Pi(u)), nu(3)+2nu(4) (Delta(u))<--2nu(4)(Delta(g)), nu(3)+2nu(5)
      (Delta(u))<--2nu(5)(Delta(g)) and nu(3)+nu(4)+nu(5)(Delta(g))<-
      nu(4)+nu(5)(Delta(u)) transitions. Sub-Q-branches (Q(e<--f) and Q(f<--e))are
      found to be resolved in the first three hot bands. More than 70 Q branch lines
      have been assigned, spread over the five hot bands. We have applied separate
      linear least squares fit to the transition wavenumbers of each Q branch/sub-Q
      branches, which have yielded values of band origins and rotational constants, in
      agreement with those derived from the analysis of the P and R branches in earlier
      work. The analysis of the sub-Q-branches have also provided values of the l
      doubling constants. This is the first report on the observation of Q branch lines
      in Delta-Delta hot bands, in the FTIR spectrum of (13)C(2)H(2).

PMID- 19111503
TI  - Green pigments of the Pompeian artists' palette.
AB  - Green colored samples on wall paintings and green powder from a pigment pot found
      in Pompeii area are investigated by micro-Raman, FT-IR and, for one sample, SEM
      EDX. To obtain the green color, green earths and malachite were used, together
      with mixture of Egyptian blue and yellow ochre. The mineralogical identification
      of the green earths has been attempted through the comparison of the vibrational
      features, discriminating between celadonite and glauconite spectra. Traces of a
      modern synthetic pigment containing copper phthalocyanine were found in a fresco
      fragment.

PMID- 19111504
TI  - Solvent influence on the infrared spectra of beta-alkoxyvinyl methyl ketones II.
      Stretching vibrations and integrated intensities of carbonyl and vinyl bands of
      (3Z,E)-4-ethoxy-1,1,1-trifluoro-5,5-dimethylhex-3-en-2-one.
AB  - Infrared spectroscopy studies of beta-alkoxyvinyl trifluoromethyl ketone, with
      structure C(2)H(5)O-C(C(CH(3))(3))CH-COCF(3) (1), in twenty three different pure
      organic solvents were undertaken to investigate the solvent-solute interactions
      and to correlate solvent properties such as Reichard's parameter and
      solvatochromic parameters of Kamlet, Abbot, and Taft with carbonyl and vinyl
      stretching vibrations and their integrated intensities of existing spatial forms.
      It was shown that conjugation in CC-CO system of the (E-s-Z-o-Z) stereoisomer is
      higher than that in this system of the (Z-s-Z-o-Z) stereoisomer. From derived
      correlations of the v (CO) and v (CC) wavenumbers with solvatochromic parameters
      of Kamlet, Abbot, and Taft it is followed that the solvent polarity influences on
      the v (CO) and v (CC) wavenumbers more intense than the solvent HBD acidity, and,
      at the same time, the influence of these solvent properties is greater for the (E
      s-Z-o-Z) stereoisomer. Analysis of derived KAT multiple regressions showed that
      the increase of the solvent polarity/polarizability (pi*) increased the
      conjugation in both stereoisomers, whereas the increase of the solvent HBD
      acidity (alpha) had opposite effect on conjugation in the (Z-s-Z-o-Z) and (E-s-Z
      o-Z) stereoisomer. In the former case conjugation was weakened, whereas in the
      latter it was enhanced. These discrepancies were the consequence of different
      structure of H-bonded complexes between enone 1 and HBD solvents. The influence
      of the solvent HBA basicity (beta) also had peculiarity. The increase of the
      solvent HBA basicity disturbs the CC-CO conjugation in the (Z-s-Z-o-Z)
      stereoisomer due to carbonyl rotation, whereas in the (E-s-Z-o-Z) stereoisomer
      such increase enhanced this conjugation and, hence, increased the v (CO) and v
      (C==C) coupling.

PMID- 19111505
TI  - FTIR spectral studies of methyltestorone in single and binary solvent systems.
AB  - The studies on the solvent effects of methyltestorone (MT) in 19 different
      organic solvents and n-C(6)H(14)/CHCl(3) binary solvents were undertaken by FTIR
      spectroscopy. The wavenumbers of carbonyl stretching vibration for MT (nu(CO)) in
      individual solvents were correlated with the empirical solvent parameters such as
      Schleyer's linear free energy equation (G-value), the solvent acceptor number
      (AN) and the linear solvation energy relationships (LSER), respectively. The
      solvent-induced carbonyl stretching vibration wavenumber shifts of MT exhibited a
      better correlation with the LSER than the other solvent parameters. With the
      increase of the volume fraction of chloroform (X(CHCl3)) in the n
      C(6)H(14)/CHCl(3) binary solvents, two kinds of nu(CO) of MT were observed and
      assigned. The formation constant (K(0)) of the interaction between MT and CHCl(3)
      and the free energy change (DeltaG(0)) of the system were calculated in the
      binary solvents by Nash's method.

PMID- 19111506
TI  - Standardisation of nucleic acid amplification assays used in clinical
      diagnostics: a report of the first meeting of the SoGAT Clinical Diagnostics
      Working Group.

PMID- 19111507
TI  - Median somatosensory evoked potential intraoperative monitoring: recommendations
      based on signal-to-noise ratio analysis.
AB  - OBJECTIVE: To form median somatosensory evoked potential (SEP) monitoring
      recommendations based on signal-to-noise ratio (SNR). METHODS: Two 1024-sweep
      right median SEP trials were recorded in 35 patients undergoing spine surgery.
      The SNR (signal power/noise power) and sweeps to reproducibility (<30% and <20%
      signal variation) were compared between the following derivations: cubital fossa
      (CF), Erb's point (EPi-EPc, EPi-M, EPi-Fz), cervical (C5S-EPc, C5S-AC, C5S-M, C5S
      Fz), subcortical (CPi-EPc, CPi-M), and cortical (CPc-EPc, CPc-M, CPc-FPz, CPc-Fz,
      CPc-CPi, CPc-CPz), where M was the mastoid. RESULTS: Higher SNR produced markedly
      faster reproducibility. The CF derivation had very high SNR and single-sweep
      reproducibility. Of cortical derivations, CPc-CPz had highest mean SNR and
      fastest overall reproducibility (median 50 and 120 sweeps to <30% and <20% signal
      variation); occasionally CPc-Fz or CPc-CPi was better. Of Erb's point and
      cervical derivations, EPi-M and C5S-M had highest mean SNR and fastest
      reproducibility. Subcortical derivations had very low mean SNR and slow or non
      reproducibility. High voltage EEG degraded cortical and subcortical derivation
      SNR and reproducibility in young children. CONCLUSIONS: The highest SNR
      derivations should be used to speed surgical feedback; slower low-SNR derivations
      should be omitted. Consequently, the CF is the best technical control and CPc-CPz
      should be the standard cortical derivation, with CPc-Fz and CPc-CPi as
      alternates. EPi-M and C5S-M are the best Erb's point and cervical derivations,
      but are optional. Subcortical derivations should be omitted. A presence/absence
      criterion or SEP omission may be indicated for some young children. SIGNIFICANCE:
      The results should influence future guidelines.

PMID- 19111508
TI  - The application of toxins and venoms to cardiovascular drug discovery.
AB  - Animal venoms contain a variety of highly selective and potent toxins, which have
      evolved over thousands/millions of years, which target vital physiological
      processes. As such, they have proven to be an excellent source of lead compounds
      for the development of therapeutic agents. In particular, a number of these venom
      components (e.g. bradykinin-potentiating peptides, sarafotoxins, natriuretic
      peptides) have profound effects on the cardiovascular system. This review article
      examines recent progress in the search for lead compounds or novel scaffolds for
      cardiovascular drug development from animal venoms.

PMID- 19111509
TI  - Degenerative spondylolisthesis of the cervical spine: analysis of 58 patients
      treated with anterior cervical decompression and fusion.
AB  - BACKGROUND CONTEXT: Degenerative spondylolisthesis has been well described as a
      disorder of the lumbar spine. Few authors have suggested that a similar disorder
      occurs in the cervical spine. To our knowledge, the present study represents the
      largest series of patients with long-term follow-up who were managed surgically
      for the treatment of degenerative spondylolisthesis of the cervical spine.
      PURPOSE: To describe the clinical presentation and radiographic findings
      associated with degenerative cervical spondylolisthesis, and to report the long
      term results of surgically managed patients. STUDY DESIGN: Analysis of 58
      patients treated with anterior cervical decompression and fusion for degenerative
      spondylolisthesis of the cervical spine. PATIENT SAMPLE: From 1974 to 2003, 58
      patients were identified as having degenerative spondylolisthesis of the cervical
      spine occurring in the absence of trauma, systemic inflammatory arthropathy, or
      congenital abnormality. These patients were identified from a database of
      approximately 500 patients with degenerative cervical spine disorders treated by
      the senior one of us. OUTCOME MEASURES: Patient outcomes were evaluated with
      regard to neurologic improvement (Nurick grade myelopathy) and osseous fusion.
      METHODS: The records of 58 patients were reviewed. The average follow-up period
      was 6.9 years (range, 2-24 years). Seventy-two cervical levels demonstrated
      spondylolisthesis. In all cases, there was radiographic evidence of facet
      degeneration and subluxation. All patients were treated with anterior cervical
      decompression and arthrodesis with iliac crest structural graft. This most
      commonly involved corpectomy of the caudal vertebrae. Three patients required
      additional posterior facet fusion. RESULTS: Fifty-eight patients demonstrated 72
      levels of involvement. The C4-C5 level was most frequently involved (43%). Two
      radiographically distinct types of listhesis were observed based on the amount of
      disc degeneration and the degree of spondylosis at adjacent levels. The average
      neurologic improvement was 1.5 Nurick grades. The overall fusion rate was 92%.
      Three patients were treated with combined anterior-posterior arthrodesis. The
      prevalence of myelopathy and instability pattern was greater in the listheses
      occurring adjacent to spondylotic levels. CONCLUSIONS: Degenerative
      spondylolisthesis is relatively common in the cervical spine. Common to all cases
      is facet arthropathy and neurologic compression. Anterior cervical decompression
      and arthrodesis appears to yield excellent union rates and neurological
      improvement in those patients having cervical degenerative spondylolisthesis and
      significant neurological sequelae who have failed nonoperative treatments.

PMID- 19111510
TI  - Clinical and radiographic assessment of transforaminal lumbar interbody fusion
      using HEALOS collagen-hydroxyapatite sponge with autologous bone marrow aspirate.
AB  - BACKGROUND CONTEXT: Studies have suggested that the use of bone marrow aspirate
      (BMA) with HEALOS (DePuy Spine, Raynham, MA), a collagen-hydroxyapatite sponge
      (CHS), is an effective substitute for autologous iliac crest bone graft when used
      in fusion procedures of the lumbar spine. PURPOSE: To assess clinical and
      radiographic outcomes after implantation of BMA/CHS in patients undergoing
      transforaminal lumbar interbody fusion (TLIF) with posterolateral fusion (PLF).
      STUDY DESIGN/SETTING: Case series radiographic outcome study. PATIENT SAMPLE:
      Twenty patients. OUTCOME MEASURES: Radiographs/computed tomography (CT) scans.
      METHODS: From September 2003 to October 2004, 20 patients (22 interbody levels)
      were implanted with BMA/CHS via TLIF/PLF with interbody cages and posterior
      pedicle screws. All patients were retrospectively identified and invited for a 2
      year prospective follow-up. Plain radiographs with dynamic films and CT scans
      were taken, and fusion was assessed in a blinded manner. RESULTS: Follow-up
      averaged 27 months (range: 24-29). Primary diagnosis included spondylolisthesis
      (17 patients), scoliosis with asymmetric collapse (2 patients), and
      postdiscectomy foraminal stenosis (1 patient). The overall fusion rate was 95%
      (21/22 levels, 19/20 patients). Anteriorly bridging bone was observed in 91% of
      the anteriorly fused levels (20/22), of which 65% (13/20) occurred through and
      around the cage and 35% (7/20) around the cage only. Unilateral or bilateral
      bridging of the posterior fusion masses was observed in 91% (20/22), with 55%
      occurring bilaterally (12/22). In 4 (18%) cases, bridging only occurred either
      posteriorly (2 cases) or anteriorly (2 cases). Complications included one deep
      wound infection. CONCLUSIONS: At the 2-year follow-up, BMA/CHS showed acceptable
      fusion rates in patients undergoing TLIF/PLF, and can be considered as an
      alternative source of graft material.

PMID- 19111511
TI  - Pharmacokinetics of kadsurenone and its interaction with cyclosporin A in rats
      using a combined HPLC and microdialysis system.
AB  - Kadsurenone is a neolignan with specific antagonistic activity of platelet
      activating factor, and is derived from the stems of Piper kadsura. To investigate
      the mechanism of hepatobiliary excretion of kadsurenone and its association with
      P-glycoprotein (P-gp), and to explore whether the hepatobiliary excretion of
      kadsurenone was associated with P-gp, a microdialysis system coupled with HPLC
      was developed to measure free-form kadsurenone in rat blood and bile. This study
      design was parallel in the following groups: six rats received kadsurenone alone
      (20 and 30 mg/kg, i.v.) as control group and the treated-group rats were co
      administered with kadsurenone and CsA; P-gp inhibitor. The microdialysis probes
      were respectively inserted into the jugular vein toward right atrium and bile
      duct of male Sprague-Dawley rats for blood and bile sampling. CsA (20mg/kg) was
      administered 10 min prior to kadsurenone administration through the femoral vein
      and the collected samples were analyzed by a HPLC system. The analytes were
      separated by a C18 column (150 x 4.6 mm I.D., 5 microm) with a mobile phase of
      acetonitrile-water (50:50, v/v) at a flow-rate of 1 mL/min. The UV detection
      wavelength was set 235 nm. The calibration curve was linear over the
      concentration range of 0.05-10 microg/mL with the coefficient of determination of
      0.997. The inter- and intra-assay accuracy and precision of the method ranged
      from -9.53% to 6.75%. The limit of detection and the limit of quantification were
      0.01 and 0.05 microg/mL, respectively. The hepatobiliary excretion ratio of
      kadsurenone was defined by dividing the values of the area under the drug
      concentration curve (AUC) for bile and blood (AUC(bile)/AUC(blood)). The results
      indicated that the hepatobiliary excretion ratio of kadsurenone on the CsA
      treated-group was 1.2+/-0.1, which was not significantly different from the group
      of kadsurenone alone (1.3+/-0.2). This fact indicates that kadsurenone went
      through hepatobiliary excretion but might not be regulated by P-gp.

PMID- 19111513
TI  - The evolution of cardiovascular stent materials and surfaces in response to
      clinical drivers: a review.
AB  - This review examines cardiovascular stent materials from the perspective of a
      range of clinical drivers and the materials that have been developed in response
      to these drivers. The review is generally chronological and outlines how stent
      materials have evolved from initial basic stainless steel devices all the way
      through to the novel biodegradable devices currently being explored. Where
      appropriate, pre-clinical or clinical data that influenced decisions and
      selections along the way is referenced. Opinions are given as to the merit and
      direction of various ongoing and future developments.

PMID- 19111512
TI  - Simultaneous determination of azaperone and azaperol in animal tissues by HPLC
      with confirmation by electrospray ionization mass spectrometry.
AB  - A simple method is described for the determination of azaperone and its
      metabolite, azaperol, in animal tissues by high-performance liquid chromatography
      with ultraviolet detection (HPLC/UV). Chromatography was performed using an ODS
      column, an acetonitrile-0.025% aqueous diethylamine mixture (2:3, v/v) as a
      mobile phase and UV detection at 250 nm. Peak heights were found linearly related
      to the concentrations injected from 0.05 to 2 microg/mL (r>0.999). Azaperone and
      azaperol spiked into several animal tissues were solubilized in 1 mol/L NaOH,
      extracted with hexane, transferred to 0.1 mol/L H(2)SO(4) and re-extracted with
      hexane in a mild basic condition. Recoveries of both compounds from 12 types of
      samples (swine muscle, swine adipose tissue, swine liver, bovine muscle, bovine
      adipose tissue, bovine liver, poultry muscle, poultry adipose tissue, poultry
      liver, bovine milk, poultry egg, and salmon muscle) were more than 72%. The lower
      limit of quantification of was 0.025 microg/g. Azaperone and azaperol at 0.1
      microg/g were confirmed by LC/MS. In conclusion, we found this method is both
      simple and useful for the determination of azaperone and azaperol in a variety of
      animal tissues for food safety and veterinary applications.

PMID- 19111514
TI  - An observation chamber for studying temperature-dependent and drug-induced events
      in live neurons using fluorescence microscopy.
AB  - Live-cell imaging chambers are used in a wide range of cell biology research.
      Recently, chambers capable of taking high-resolution and time-lapse images of
      live cells have been developed and become commercially available. However,
      because most of these chambers are designed to maintain a thermally stable
      environment for the cells under study, it is usually very difficult to use them
      to study temperature-dependent cellular events. Here we report the development of
      a chamber that is able to be used for the continuous monitoring of live neurons
      under most commercially available upright epifluorescence and confocal
      microscopes and in which the temperature and composition of the medium
      surrounding the neurons can be changed rapidly and reversibly. This live-cell
      observation chamber has been used successfully with cultured rat hippocampal
      neurons to study temperature-dependent changes in the dynamics of the microtubule
      cytoskeleton using fluorescence recovery after photobleaching (FRAP) together
      with the localization of alpha-tubulin in the dendritic spines. The success of
      these observations demonstrates the usefulness and applicability of the live-cell
      observation chamber described here to a wide range of cell biology experiments.

PMID- 19111515
TI  - A dual-acceptor time-resolved Foster resonance energy transfer assay for
      simultaneous determination of thyroid hormone regulation of corepressor and
      coactivator binding to the thyroid hormone receptor: Mimicking the cellular
      context of thyroid hormone action.
AB  - Previously, we reported the development of two in vitro time-resolved Foster
      resonance energy transfer (tr-FRET)-based assays for evaluating the potency and
      efficacy of different ligands of thyroid hormone receptor (TR) for regulating the
      recruitment of coregulators. We could measure independently, in separate assays,
      both the recruitment of SRC3 (steroid receptor coactivator 3, a transcriptional
      coactivator) and the dissociation of NCoR (nuclear receptor corepressor, a
      transcriptional corepressor) from a TR*retinoid X receptor (RXR) heterodimer
      bound to a DR+4 thyroid hormone response element (TRE). Here, by using the
      distinct emission peaks of Tb(3+), the donor fluorophore used to label the TRE
      bound TR*RXR heterodimers, and selecting two distinct acceptor fluorophores,
      fluorescein and cyanine 5, to label of NCoR and SRC3, respectively, we have
      integrated our previous two assay formats into a single assay. Thus, we can
      measure the potency of TR ligands simultaneously for NCoR dissociation and SRC3
      recruitment activities in a system that mimics many features of the cellular
      context of TR action. The performance of this dual assay was tested with a known,
      highly potent physiological TR ligand, triiodothyronine (T(3)), and with a
      synthetic TR antagonist, NH-3. Measured potencies and efficacies of these two TR
      ligands from this dual assay are highly comparable to those obtained from the two
      independent assays. Thus, this dual-acceptor tr-FRET assay further simplifies the
      measurement of ligand-modulated TR-coregulator interactions and should improve
      the overall efficiency of the screening process of TR drug discovery programs.

PMID- 19111516
TI  - Determination of nanomolar uric and ascorbic acids using enlarged gold
      nanoparticles modified electrode.
AB  - Individual and simultaneous determination of 50nM uric acid (UA) and ascorbic
      acid (AA) using enlarged, citrate-stabilized gold nanoparticles (AuNPs) self
      assembled to 2,5-dimercapto-1,3,4-thiadiazole (DMT) monolayer modified Au
      (Au/DMT) electrode by an amperometric method is described for the first time.
      Self-assembly of AuNPs on the electrode surface was confirmed by atomic force
      microscopy (AFM), attenuated total reflectance FT-IR and diffuse reflectance
      spectral measurements. The electron transfer reaction (ETR) of [Fe(CN)(6)](3-/4-)
      was blocked at Au/DMT electrode, whereas it was restored with a peak separation
      of 200mV after the attachment of AuNPs on the Au/DMT (Au/DMT/AuNPs) electrode,
      which was confirmed from the ETR of the [Fe(CN)(6)](3-/4-) redox couple. When the
      self-assembled AuNPs were enlarged by hydroxylamine seeding, the ETR of
      [Fe(CN)(6)](3-/4-) was improved significantly with a peak separation of 100mV.
      Tapping mode AFM showed that the average size of the enlarged-AuNPs (E-AuNPs) was
      50-70nm. The E-AuNPs modified electrode catalyzes the oxidation of AA and UA,
      separates their voltammetric signals by 200mV, and has excellent sensitivity
      towards AA and UA with a detection limit of 50nM. The practical application of
      the modified electrode was demonstrated by measuring the concentration of UA in
      blood serum and urine.

PMID- 19111517
TI  - A tetracycline repressor-based mammalian two-hybrid system to detect protein
      protein interactions in vivo.
AB  - A mammalian two-hybrid system (termed as trM2H) was developed to detect protein
      protein interactions in vivo, based on the reconstitution of the functions the of
      tetracycline repressor (TetR). The system is sensitive enough to detect protein
      protein interactions with K(d) up to 55microM in mammalian cells, and the system
      can be regulated by small molecules. This system can be used as an efficient
      genetic selection system to map protein-protein interactions in mammalian cells.

PMID- 19111518
TI  - Direct and continuous assay for prolyl 4-hydroxylase.
AB  - Prolyl 4-hydroxylase (P4H) is a nonheme iron dioxygenase that catalyzes the
      posttranslational hydroxylation of (2S)-proline (Pro) residues in protocollagen
      strands. The resulting (2S,4R)-4-hydroxyproline (Hyp) residues are essential for
      the folding, secretion, and stability of the collagen triple helix. P4H uses
      alpha-ketoglutarate and O2 as cosubstrates, and forms succinate and CO2 as well
      as Hyp. Described herein is the first assay for P4H that continuously and
      directly detects turnover of the proline-containing substrate. This assay is
      based on (2S,4S)-4-fluoroproline (flp), a proline analogue that is transformed
      into (2S)-4-ketoproline (Kep) and inorganic fluoride by P4H. The fluoride ion,
      and thus turnover by P4H, is detected by a fluoride ion-selective electrode.
      Using this assay, steady-state kinetic parameters for the human P4H-catalyzed
      turnover of a flp-containing peptide were determined and found to be comparable
      to those obtained with a discontinuous HPLC-based assay. In addition, this assay
      can be used to characterize P4H variants, as demonstrated by a comparison of
      catalysis by D414A P4H and the wild-type enzyme. Finally, the use of the assay to
      identify small-molecule inhibitors of P4H was verified by an analysis of
      catalysis in the presence of 2,4-pyridine dicarboxylate, an analogue of alpha
      ketoglutarate. Thus, the assay described herein could facilitate biochemical
      analyses of this essential enzyme.

PMID- 19111519
TI  - Genotyping of celiac disease-related-risk haplotypes using a closed-tube
      polymerase chain reaction analysis of dried blood and saliva disk samples.
AB  - Expansion of molecular diagnostics more widely into clinical routines requires
      simplified methods allowing automation. We developed a homogeneous, multilabel
      polymerase chain reaction (PCR) method based on time-resolved fluorometry, and
      studied the use of dried disk samples in PCR. Celiac disease-related HLA-DQA1*05,
      HLA-DQB1*02, and HLA-DQB1*0302 genotyping was used to verify the method with
      blood and saliva samples dried on S&S 903 and IsoCode sample collection papers.
      Three sample preparation procedures, including manufacturer's manual elution, an
      automated elution, and direct use of disk samples, were compared using dried disk
      samples. The three procedures gave successful amplification and correct
      genotyping results. Owing to the simplicity of the direct use of disk samples in
      PCR, this method was chosen for the subsequent homogeneous analysis of blood
      (n=194) and saliva (n=30) disk samples on S&S 903 paper. The results revealed
      that, in addition to DNA samples (n=29), both blood and saliva disk samples were
      successfully amplified and genotyped using the homogeneous PCR assays for HLA
      DQA1 and HLA-DQB1. The homogeneous PCR assays developed provide a useful tool to
      genotype celiac disease-related HLA-DQA1*05, HLA-DQB1*02, and HLA-DQB1*0302
      alleles. Furthermore, the method provides a direct way to perform a closed-tube
      PCR analysis of dried blood and saliva disk samples enabling simple automation.

PMID- 19111520
TI  - Exploring blocking assays using Octet, ProteOn, and Biacore biosensors.
AB  - We demonstrate the use of label-free real-time optical biosensors in competitive
      binding assays by epitope binning a panel of antibodies. We describe three assay
      orientations that we term in tandem, premix, and classical sandwich blocking, and
      we perform each of them on three platforms: ForteBio's Octet QK, Bio-Rad's
      ProteOn XPR36, and GE Healthcare's Biacore 3000. By testing whether antibodies
      block one another's binding to their antigen in a pairwise fashion, we establish
      a blocking profile for each antibody relative to the others in the panel. The
      blocking information is then used to create "bins" of antibodies with similar
      epitopes. The advantages and disadvantages of each biosensor, factors to consider
      when deciding on the most appropriate blocking assay orientation for a particular
      interaction system, and tips for dealing with ambiguous data are discussed. The
      data from our different assay orientations and biosensors agree very well,
      establishing these machines as valuable tools for characterizing antibody
      epitopes and multiprotein complexes of biological significance.

PMID- 19111521
TI  - Antibiotics LL-Z1272 identified as novel inhibitors discriminating bacterial and
      mitochondrial quinol oxidases.
AB  - To counter antibiotic-resistant bacteria, we screened the Kitasato Institute for
      Life Sciences Chemical Library with bacterial quinol oxidase, which does not
      exist in the mitochondrial respiratory chain. We identified five prenylphenols,
      LL-Z1272beta, gamma, delta, epsilon and zeta, as new inhibitors for the
      Escherichia coli cytochrome bd. We found that these compounds also inhibited the
      E. coli bo-type ubiquinol oxidase and trypanosome alternative oxidase, although
      these three oxidases are structurally unrelated. LL-Z1272beta and epsilon
      (dechlorinated derivatives) were more active against cytochrome bd while LL
      Z1272gamma, delta, and zeta (chlorinated derivatives) were potent inhibitors of
      cytochrome bo and trypanosome alternative oxidase. Thus prenylphenols are useful
      for the selective inhibition of quinol oxidases and for understanding the
      molecular mechanisms of respiratory quinol oxidases as a probe for the quinol
      oxidation site. Since quinol oxidases are absent from mammalian mitochondria, LL
      Z1272beta and delta, which are less toxic to human cells, could be used as lead
      compounds for development of novel chemotherapeutic agents against pathogenic
      bacteria and African trypanosomiasis.

PMID- 19111522
TI  - Neurological phenotype and reduced lifespan in heterozygous Tim23 knockout mice,
      the first mouse model of defective mitochondrial import.
AB  - The Tim23 protein is the key component of the mitochondrial import machinery. It
      locates to the inner mitochondrial membrane and its own import is dependent on
      the DDP1/TIM13 complex. Mutations in human DDP1 cause the Mohr-Tranebjaerg
      syndrome (MTS/DFN-1; OMIM #304700), which is one of the two known human diseases
      of the mitochondrial protein import machinery. We created a Tim23 knockout mouse
      from a gene trap embryonic stem cell clone. Homozygous Tim23 mice were not
      viable. Heterozygous F1 mutants showed a 50% reduction of Tim23 protein in
      Western blot, a neurological phenotype and a markedly reduced life span.
      Haploinsufficiency of the Tim23 mutation underlines the critical role of the
      mitochondrial import machinery for maintaining mitochondrial function.

PMID- 19111523
TI  - Are specific nonannular cholesterol binding sites present in G-protein coupled
      receptors?
AB  - The G-protein coupled receptors (GPCRs) are the largest class of molecules
      involved in signal transduction across membranes, and represent major drug
      targets in all clinical areas. Membrane cholesterol has been reported to have a
      modulatory role in the function of a number of GPCRs. Interestingly, recently
      reported crystal structures of GPCRs have shown structural evidence of
      cholesterol binding sites. Two possible mechanisms have been previously suggested
      by which membrane cholesterol could influence the structure and function of GPCRs
      (i) through a direct/specific interaction with GPCRs, which could induce a
      conformational change in the receptor, or (ii) through an indirect way by
      altering the membrane physical properties in which the receptor is embedded or
      due to a combination of both. We discuss here a novel mechanism by which membrane
      cholesterol could affect structure and function of GPCRs and propose that
      cholesterol binding sites in GPCRs could represent 'nonannular' binding sites.
      Interestingly, previous work from our laboratory has demonstrated that membrane
      cholesterol is required for the function of the serotonin1A receptor, which could
      be due to specific interaction of the receptor with cholesterol. Based on these
      results, we envisage that there could be specific/nonannular cholesterol binding
      site(s) in the serotonin1A receptor. We have analyzed putative cholesterol
      binding sites from protein databases in the serotonin1A receptor, a
      representative GPCR, for which we have previously demonstrated specific
      requirement of membrane cholesterol for receptor function. Our analysis shows
      that cholesterol binding sites are inherent characteristic features of
      serotonin1A receptors and are conserved over evolution. Progress in deciphering
      molecular details of the nature of GPCR-cholesterol interaction in the membrane
      would lead to better insight into our overall understanding of GPCR function in
      health and disease, thereby enhancing our ability to design better therapeutic
      strategies to combat diseases related to malfunctioning of GPCRs.

PMID- 19111524
TI  - A peptide derived from the putative transmembrane domain in the tail region of E.
      coli toxin hemolysin E assembles in phospholipid membrane and exhibits lytic
      activity to human red blood cells: plausible implications in the toxic activity
      of the protein.
AB  - Hemolysin E (HlyE), a pore-forming protein-toxin and a potential virulence factor
      of Escherichia coli, exhibits cytotoxic activity to mammalian cells. However,
      very little is known about how the different individual segments contribute in
      the toxic activity of the protein. Toward this end, the role of a 33-residue
      segment comprising the amino acid region 88 to 120, which contains the putative
      transmembrane domain in the tail region of HlyE has been addressed in the toxic
      activity of the protein-toxin by characterizing the related wild type and mutant
      peptides and the whole protein. Along with the 33-residue wild type peptide, H
      88, two mutants of the same size were synthesized; in one mutant a conserved
      valine at 89th position was replaced by aspartic acid and in the other both
      glycine and valine at the 88th and 89th positions were substituted by aspartic
      acid residues. These mutations were also incorporated in the whole toxin HlyE.
      Results showed that only H-88 but not its mutants permeabilized both lipid
      vesicles and human red blood cells (hRBCs). Interestingly, while H-88 exhibited a
      moderate lytic activity to human red blood cells, the mutants were not active.
      Drastic reduction in the depolarization of hRBCs and hemolytic activity of the
      whole toxin HlyE was also observed as a result of the same double and single
      amino acid substitution in it. The results indicate an important role of the
      amino acid segment 88-120, containing the putative transmembrane domain of the
      tail region of the toxin in the toxic activity of hemolysin E.

PMID- 19111525
TI  - Combined treatment of neurotrophin-3 gene and neural stem cells is ameliorative
      to behavior recovery of Parkinson's disease rat model.
AB  - Neural stem cell transplantation therapy was developed for replacing lost or
      damaged neural cells for the neurodegenerative disease, including Parkinson's
      disease (PD), in which dopaminergic neuron cells are lost. The growth factor,
      neurotrophin-3(NT-3), has been shown to promote neuroregeneration,
      differentiation and migration during brain development. In this report, we
      construct rat neural stem cells that express neurotrophin-3 endogenously (rNSC
      NT3) and transplant them into 6-hydroxydopamine (6-OHDA)-treated Parkinsonian
      rats. Molecular approaches including quantitative real time PCR, Western blot and
      immunocytochemistry were used to identify the expression of NT-3 and the
      differentiation of planted cells. Behavioral recover was also tested. The result
      indicated that combined treatment of neurotrophin-3 gene and neural stem cells
      had a functional impact on reversing the main symptoms of the Parkinson's disease
      that significantly reduced apomorphine-induced rotational asymmetry and improved
      spatial learning ability. The rNSCs-NT3 is able to differentiate into
      dompaminergic neuron in the ventral tegmental area (VTA) and the medial forebrain
      bundle (MFB), and migrated around the lesion site. Endogenous expressed NT-3
      exerts induction and trophic effects on neural stem cells. The rNSCs-NT3 showed
      higher activity than the rNSCs in regenerating tyrosine hydroxylase positive cell
      numbers and migrating distance, behavior improving in this dopa-deficit rat
      model. These findings suggest that the neural stem cells expressed NT-3
      endogenously would be a better graft candidate for the treatment of Parkinson's
      disease.

PMID- 19111526
TI  - Mapping interference resolution across task domains: a shared control process in
      left inferior frontal gyrus.
AB  - Work in functional neuroimaging has mapped interference resolution processing
      onto left inferior frontal regions for both verbal working memory and a variety
      of semantic processing tasks. The proximity of the identified regions from these
      different tasks suggests the existence of a common, domain-general interference
      resolution mechanism. The current research specifically tests this idea in a
      within-subject design using fMRI to assess the activation associated with
      variable selection requirements in a semantic retrieval task (verb generation)
      and a verbal working memory task with a trial-specific proactive interference
      manipulation (recent-probes). High interference trials on both tasks were
      associated with activity in the midventrolateral region of the left inferior
      frontal gyrus, and the regions activated in each task strongly overlapped. The
      results indicate that an elemental component of executive control associated with
      interference resolution during retrieval from working memory and from semantic
      memory can be mapped to a common portion of the left inferior frontal gyrus.

PMID- 19111527
TI  - Intraventricular orexin-A improves arousal and early EEG entropy in rats after
      cardiac arrest.
AB  - The recovery of arousal after cardiac arrest (CA) is associated with evolution
      from electroencephalographic (EEG) burst-suppression to continuous activity.
      Orexin-A elicits arousal EEG during anesthetic burst-suppression. We hypothesized
      that orexin-A would improve arousal and EEG entropy after CA. Eighteen Wistar
      rats were subjected to 7-minute asphyxial CA and resuscitation. Rats were divided
      into treatment (n=9) and control (n=9) groups. Twenty minutes after
      resuscitation, the treatment group received 0.1 mL of 1 nM orexin-A
      intraventricularly, while controls received saline. EEG was quantified using
      Information Quantity (IQ), a measure of entropy validated for detection of burst
      suppression and arousal patterns. IQ values range from 0 to 1.0. Arousal was
      quantified using the neurological deficit scale (NDS). The ischemic neuronal
      fraction of hippocampus CA1 and cortex was histologically determined. Baseline
      and post-resuscitation characteristics were similar between the groups. The NDS
      score (mean+/-SD) at 4 h was higher in the orexin-A group compared to controls
      (57.3+/-5.8 vs. 40.7+/-5.9, p<0.02), but scores were similar at 72 h. Burst
      frequency was similar in both groups but the orexin-A group demonstrated higher
      IQ values compared to controls beginning within 10 min. IQ values remained
      significantly higher in the orexin-A group for the first 120 min (p=0.008) and
      subsequently converged. The ischemic neuronal fraction was similar between groups
      in cortex (p=0.54) and hippocampus CA1 (p=0.14). In rats resuscitated from CA,
      orexin-A transiently increased arousal and EEG entropy without worsening ischemic
      neuronal injury. The role of orexin-A in recovery of arousal after CA deserves
      further investigation.

PMID- 19111528
TI  - An investigation of the C77G and C772T variations within the human protein
      tyrosine phosphatase receptor type C gene for association with multiple sclerosis
      in an Australian population.
AB  - Multiple sclerosis (MS) is a common cause of neurological disability in young
      adults. The disease generally manifests in early to middle adulthood and causes
      various neurological deficits. Autoreactive T lymphocytes and their associated
      antigens have long been presumed important features of MS pathogenesis. The
      Protein tyrosine phosphatase receptor type C gene (PTPRC) encodes the T-cell
      receptor CD45. Variations within PTPRC have been previously associated with
      diseases of autoimmune origin such as type 1 diabetes mellitus and Graves'
      disease. We set out to investigate two variants within the PTPRC gene, C77G and
      C772T in subjects with MS and matched healthy controls to determine whether
      significant differences exist in these markers in an Australian population. We
      employed high resolution melt analysis (HRM) and restriction length polymorphism
      (RFLP) techniques to determine genotypic and allelic frequencies. Our study found
      no significant difference between frequencies for PTPRC C77G by either genotype
      (Chi(2)=0.65, P=0.72) or allele (Chi(2)=0.48, P=0.49). Similarly, we did not find
      evidence to suggest an association between PTPRC C772T by genotype (Chi(2)=1.06,
      P=0.59) or allele (Chi(2)=0.20, P=0.66). Linkage disequilibrium (LD) analysis
      showed strong linkage disequilibrium between the two tested markers (D'=0.9970,
      SD=0.0385). This study reveals no evidence to suggest that these markers are
      associated with MS in the tested Australian Caucasian population. Although the
      PTPRC gene has a significant role in regulating CD4+ and CD8+ autoreactive T
      cells, interferon-beta responsiveness, and potentially other important processes,
      our study does not support a role for the two tested variants of this gene in MS
      susceptibility in the Australian population.

PMID- 19111530
TI  - Association of parental hyperhomocysteinemia and C677T Methylene tetrahydrofolate
      reductase (MTHFR) polymorphism with recurrent pregnancy loss.
AB  - OBJECTIVES: To investigate the association of parental hyperhomocysteinemia,
      C677T Methylene tetrahydrofolate reductase (MTHFR) polymorphism and DNA damage
      with recurrent pregnancy loss (RPL). DESIGN AND METHODS: A case-control study.
      Reverse phase HPLC, PCR-RFLP and Cytokinesis blocked micronuclei assay were used
      to assess total plasma homocysteine, C677T MTHFR polymorphism and DNA damage
      respectively. Student t-test, ANOVA and Fisher exact test were used for
      statistical analysis. RESULTS: Maternal [mean: 11.6+/-5.0 versus 8.6+/-4.2
      micromol/L, odds ratio (OR): 4.48] and paternal [mean: 19.6+/-9.5 versus 14.2+/
      7.4 micromol/L, OR: 6.92] hyperhomocysteinemia, paternal age [OR: 1.16], paternal
      MTHFR 677T allele [OR: 2.30] and DNA damage were found to increase the risk for
      RPL. DNA damage showed positive correlation with plasma homocysteine and MTHFR
      677T allele. CONCLUSIONS: Parental hyperhomocysteinemia, paternal age, paternal
      C677T MTHFR polymorphism and DNA damage are risk factors for RPL. DNA damage
      showed positive correlation with plasma homocysteine and MTHFR 677T allele.

PMID- 19111529
TI  - Normal feeding and body weight in Fischer 344 rats lacking the cholecystokinin-1
      receptor gene.
AB  - A large body of evidence has demonstrated that one mechanism by which
      cholecystokinin (CCK) inhibits food intake through activation of CCK1 receptors
      (CCK1R) on vagal afferent neurons that innervate the gastrointestinal tract and
      project to the hindbrain. OLETF rats, which carry a spontaneous null mutation of
      the CCK1R, are hyperphagic, obese, and predisposed to type 2 diabetes. Recently,
      by introgressing the OLETF-derived, CCK1R-null gene onto a Fischer 344 genetic
      background, we have been able to generate a CCK1R-deficient, congenic rat strain,
      F344.Cck1r(-/-), that in contrast to OLETF rats, possesses a lean and
      normoglycemic phenotype. In the present study, the behavioral and neurobiological
      phenotype of this rat strain was characterized more fully. As expected,
      intraperitoneal injections of CCK-8 inhibited intake of chow and Ensure Plus and
      induced Fos responses in the area postrema and the gelatinosus, commissural and
      medial subdivisions of the nucleus tractus solitarius of wild-type
      F344.Cck1r(+/+) rats, whereas CCK-8 was without effect on food intake or Fos
      induction in the F344.Cck1r(-/-) rats. F344.Cck1r(-/-) and F344.Cck1r(+/+) rats
      did not differ in body weight and showed comparable weight gain when maintained
      on Ensure Plus for 2 weeks. Also, no difference was found in 24-h food intake,
      and dark-phase meal frequency or meal size between F344.Cck1r(+/+) and
      F344.Cck1r(-/-) rats. As expected, blockade of endogenous CCK action at CCK1R
      increased food intake and blocked the effects of peripheral CCK-8 in wild-type
      F344.Cck1r(+/+) rats. These results confirm that in rats with a F344 background,
      CCK-1R mediates CCK-8-induced inhibition of food intake and Fos activation in the
      hindbrain and demonstrate that selective genetic ablation of CCK1R is not
      associated with altered meal patterns, hyperphagia, or excessive weight gain on a
      palatable diet.

PMID- 19111531
TI  - Association of a 27-bp repeat polymorphism in intron 4 of endothelial
      constitutive nitric oxide synthase gene with hypertension in a Tunisian
      population.
AB  - OBJECTIVES: Nitric oxide (NO) produced by endothelial nitric oxide synthase
      (eNOS) mediates endothelium-dependent vasodilatation and antithrombotic action.
      Controversial results regarding the association of eNOS gene (NOS3) polymorphisms
      with hypertension have been reported. In the present study, we examined a
      possible association between the 27-base pair (bp) repeat polymorphism in intron
      4 of the NOS3 gene and hypertension in a sample of the Tunisian population.
      DESIGN AND METHODS: A total of 295 Tunisian patients with hypertension and 395
      healthy controls were included in the study. The NOS3 gene intron 4a4b variable
      number of tandem repeats polymorphism was analyzed by PCR. RESULTS: A significant
      differences in genotype distribution and allele frequency was observed between
      patients and controls. Patients with hypertension had a frequency of 6.4% for the
      4a4a genotype, 32.7% for the 4a4b genotype and 60.9% for the 4b4b genotype. The
      controls had a frequency of only 2.3% for the 4a4a genotype, 28.4% for the 4a4b
      genotype and 69.4% for the 4b4b genotype (chi(2)=11.81, p=0.003). The
      hypertension patient group showed a significant higher frequency of the 4a allele
      compared to the controls (0.23 vs. 0.16; chi(2)=8.61, p=0.003). The odds ratio of
      hypertension for 4a vs 4b allele frequencies was statistically significant 1.66
      [1.09-2.53] at 95% CI, p=0.01 in males, whereas it was non-significant in females
      (1.23 [0.84-1.81], p=0.26). CONCLUSION: The present study showed a significant
      and independent association between the NOS34a4b gene polymorphism (presence of
      4a allele) and hypertension in the Tunisian population.

PMID- 19111534
TI  - Paracrine regulation of the resumption of oocyte meiosis by endothelin-1.
AB  - Mammalian oocytes remain dormant in the diplotene stage of prophase I until the
      resumption of meiosis characterized by germinal vesicle breakdown (GVBD)
      following the preovulatory gonadotropin stimulation. Based on genome-wide
      analysis of peri-ovulatory DNA microarray to identify paracrine hormone-receptor
      pairs, we found increases in ovarian transcripts for endothelin-1 and endothelin
      receptor type A (EDNRA) in response to the preovulatory luteinizing hormone
      (LH)/human chorionic gonadotropin (hCG) stimulation. Immunohistochemical analyses
      demonstrated localization of EDNRA in granulosa and cumulus cells. In cultured
      preovulatory follicles, treatment with endothelin-1 promoted oocyte GVBD. The
      stimulatory effect of endothelin-1 was blocked by cotreatment with antagonists
      for the type A, but not related type B, receptor. The stimulatory effect of hCG
      on GVBD was partially blocked by the same antagonist. The endothelin-1 promotion
      of GVBD was found to be mediated by the MAPK/ERK pathway but not by the
      inhibitory G protein. Studies using cumulus-oocyte complexes and denuded oocytes
      demonstrated that the endothelin-1 actions are mediated by cumulus cells.
      Furthermore, intrabursal administration with endothelin-1 induced oocyte GVBD in
      preovulatory follicles. Our findings demonstrate a paracrine role of endothelin-1
      in the induction of the resumption of meiosis and provide further understanding
      on the molecular mechanisms underlying the nuclear maturation of oocytes induced
      by the preovulatory LH surge.

PMID- 19111533
TI  - Transcription factor Lmo4 defines the shape of functional areas in developing
      cortices and regulates sensorimotor control.
AB  - Proper formation of the shape and size of cortical functional areas is essential
      for complex brain function, including sensory perception and motor control. Our
      previous work identified the transcription factor Lim domain only 4 (Lmo4), a
      regulator in calcium-dependent gene transcription, that has unique, region
      specific expression in postnatal mouse cortices with high expression anteriorly
      and posteriorly but very low expression in between. Here we report that Lmo4
      expression coincides with the timing of the development of the somatosensory
      barrel field. Lmo4 cortical deletion causes changes in expression patterns of
      cortical regional markers and results in rostro-medial shrinkage but not rostral
      or caudal shift of the somatosensory barrel subfield. Fine regulation of accurate
      shape of the barrel subfield by Lmo4, as well as Lmo4-mediated calcium-dependent
      gene expression, is critical for normal brain functions, as Lmo4-deficient mice
      display impaired sensorimotor performance. Moreover, even though Lmo4 has broad
      expression in the central nervous system, it plays a subtle role in the
      development of non-cortical regions. Our results reveal a new mechanism of
      cortical area formation and normal sensorimotor control that is regulated by
      genes with region-specific expression in the developing cortex.

PMID- 19111532
TI  - ELT-2 is the predominant transcription factor controlling differentiation and
      function of the C. elegans intestine, from embryo to adult.
AB  - Starting with SAGE-libraries prepared from C. elegans FAC-sorted embryonic
      intestine cells (8E-16E cell stage), from total embryos and from purified
      oocytes, and taking advantage of the NextDB in situ hybridization data base, we
      define sets of genes highly expressed from the zygotic genome, and expressed
      either exclusively or preferentially in the embryonic intestine or in the
      intestine of newly hatched larvae; we had previously defined a similarly
      expressed set of genes from the adult intestine. We show that an extended TGATAA
      like sequence is essentially the only candidate for a cis-acting regulatory motif
      common to intestine genes expressed at all stages. This sequence is a strong ELT
      2 binding site and matches the sequence of GATA-like sites found to be important
      for the expression of every intestinal gene so far analyzed experimentally. We
      show that the majority of these three sets of highly expressed intestinal
      specific/intestinal-enriched genes respond strongly to ectopic expression of ELT
      2 within the embryo. By flow-sorting elt-2(null) larvae from elt-2(+) larvae and
      then preparing Solexa/Illumina-SAGE libraries, we show that the majority of these
      genes also respond strongly to loss-of-function of ELT-2. To test the
      consequences of loss of other transcription factors identified in the embryonic
      intestine, we develop a strain of worms that is RNAi-sensitive only in the
      intestine; however, we are unable (with one possible exception) to identify any
      other transcription factor whose intestinal loss-of-function causes a phenotype
      of comparable severity to the phenotype caused by loss of ELT-2. Overall, our
      results support a model in which ELT-2 is the predominant transcription factor in
      the post-specification C. elegans intestine and participates directly in the
      transcriptional regulation of the majority (>80%) of intestinal genes. We present
      evidence that ELT-2 plays a central role in most aspects of C. elegans intestinal
      physiology: establishing the structure of the enterocyte, regulating enzymes and
      transporters involved in digestion and nutrition, responding to environmental
      toxins and pathogenic infections, and regulating the downstream intestinal
      components of the daf-2/daf-16 pathway influencing aging and longevity.

PMID- 19111535
TI  - ZFPIP/Zfp462 is maternally required for proper early Xenopus laevis development.
AB  - ZFPIP (Zinc Finger Pbx1 Interacting Protein) has been recently identified in our
      laboratory in a yeast two hybrid screen using an embryonic mouse cDNA library and
      PBX1 as a bait. This gene encodes a large protein (250 kDa) that contains a
      bipartite NLS, numerous C2H2 zinc fingers and is highly conserved amongst
      vertebrates. In order to address the role of ZFPIP during embryonic development,
      we analysed the expression pattern of the gene and performed morpholinos
      injections into Xenopus laevis embryos. We first showed that the ZFPIP protein
      was maternally present in oocytes. Then, ZFPIP was detected from morula to
      neurula stages in the nucleus of the cells, with a gradient from animal to
      vegetal pole. By injection of ZFPIP morpholinos, we showed that morphant embryos
      were unable to undergo proper gastrulation and subsequently exhibited a
      persistent opened blastopore. Analysis of molecular and cellular events that were
      altered in morphant embryos highlighted an impairment of cell division processes
      as illustrated by atypical mitosis with aberrant metaphase, anaphase or
      telophase, incomplete chromosome segregation or conjointed nuclei. The overall
      data presented here demonstrated that ZFPIP was a major developing gene that acts
      in the very first steps of embryonic development of Xenopus laevis.

PMID- 19111536
TI  - Effects of (-) epigallocatechin-3-gallate on Na(+) currents in rat dorsal root
      ganglion neurons.
AB  - The natural product (-) epigallocatechin-3-gallate (EGCG) is the major
      polyphenolic constituent found in green tea. Dorsal root ganglion neurons are
      primary sensory neurons, and express tetrodotoxin-sensitive and tetrodotoxin
      resistant Na(+) currents, which are both actively involved in the generation and
      propagation of nociceptive signals. Effects of EGCG on tetrodotoxin-sensitive and
      tetrodotoxin-resistant Na(+) currents in rat dorsal root ganglion neurons were
      investigated using the whole-cell variation of the patch-clamp techniques. EGCG
      inhibited both types of Na(+) currents potently and in a concentration-dependent
      manner. The apparent dissociation constant, K(d), was estimated to be 0.74 and
      0.80 microM for tetrodotoxin-sensitive and tetrodotoxin-resistant Na(+) currents,
      respectively. (-) Epigallocatechin (EGC) was far less potent to inhibit Na(+)
      currents than EGCG, suggesting that gallate moiety of EGCG is an important
      functional group to modulate Na(+) currents. EGCG had little or no effect on the
      activation or steady-state inactivation voltage of either type of Na(+) current.
      EGCG simply reduced the availability of Na(+) channels for activation. Thus, EGCG
      appears to bind to resting Na(+) channels to inhibit them. EGCG slowed the
      recovery of tetrodotoxin-sensitive Na(+) current from inactivation. The property
      of EGCG to inhibit sensory Na(+) currents can be utilized to develop an analgesic
      agent.

PMID- 19111537
TI  - Phenotypic characterization of the infiltrating immune cells in normal prostate,
      benign nodular prostatic hyperplasia and prostatic adenocarcinoma.
AB  - BACKGROUND: Immune cell infiltrate is a constant feature in normal prostate,
      benign nodular prostatic hyperplasia and prostatic adenocarcinoma. This study
      elaborates on the cells of the immune system present in normal prostate, benign
      nodular prostatic hyperplasia and prostatic adenocarcinoma. HYPOTHESIS: Here, we
      hypothesized that "the development of benign nodular prostatic hyperplasia and
      prostatic adenocarcinoma is associated with numeric alterations of the immune
      cell infiltrate". MATERIALS AND METHODS: A total of 50 transurethral prostatic
      resection specimens, each entailing normal prostate, benign nodular prostatic
      hyperplasia and high grade prostatic adenocarcinoma were evaluated for the
      density and phenotype of the immune cells using immunohistological methods and
      mouse monoclonal antibodies decorating T cells (CD3), histiocytes (CD68) and B
      lymphocytes (CD20). RESULTS: Immune cell infiltrate was composed of T cells,
      histiocytes and B-lymphocytes. CD(+)3 T lymphocytes and CD68(+) cells were the
      predominant cell populations. We observed variations in the density of the immune
      cells among the normal prostate, benign nodular prostatic hyperplasia and high
      grade prostatic adenocarcinoma. Compared with normal prostate, benign nodular
      prostatic hyperplasia had a statistically significant high density of immune
      cells (3.4+/-0.4versus 13.5+/-1.0, P<0.00). In contrast, a significant decrease
      in the counts of these cells was observed in high-grade prostatic adenocarcinoma
      compared to benign nodular prostatic hyperplasia (13.5+/-1.0 versus 5.2+/-0.3,
      P<0.01). CONCLUSIONS: The increased density of immune cells (predominantly CD(+)3
      T cells) in benign nodular prostatic hyperplasia suggests that the initial
      response to cellular damage is mediated by cell-mediated immunity. The decreased
      density of immune cells in high-grade prostatic adenocarcinoma may reflect
      immunosuppression. The underlying mechanisms of these numeric variations are open
      for further investigations.

PMID- 19111538
TI  - Serial monitoring of humoral antibody-mediated rejection of cardiac allografts by
      C4d staining of interstitial capillaries.
AB  - C4d "staining" of interstitial capillaries of endomyocardial biopsies serves as
      an indicator of a humoral component of cardiac allograft rejection. In the
      present study, two cardiac allograft recipients were monitored serially for both
      cellular and humoral rejection. Cellular rejection, evaluated by light
      microscopy, and humoral rejection, judged by C4d immunofluorescent "staining",
      were treated with appropriate immunosuppressants. Weekly serial biopsies of the
      first patient revealed maximal humoral rejection (3+) after 1 week but diminished
      to 2+ thereafter. Cellular rejection was graded as 3A after 3 weeks but declined
      steadily to negligible cellular rejection through week 15. Whereas, cellular
      rejection peaked at 14-21 days, humoral rejection was greatest in the early post
      transplant period. Biopsies of the second patient for 12 weeks revealed grade 1A
      to 1B moderate cellular rejection. Humoral rejection peaked at 3+ "staining" for
      C4d after 1 week transplant, and then wavered between 2+ (moderate "staining")
      and 1+ (weak "staining"). Results revealed the significance not only of
      traditional light microscopy in evaluating the severity of cellular rejection in
      endomyocardial biopsies of cardiac allotransplants, but also the value of C4d
      immunofluorescent "staining" of interstitial capillaries as an indicator of
      humoral rejection episodes, which may require modified therapy.

PMID- 19111539
TI  - TIMP-3 and MMP-3 contribute to delayed inflammation and hippocampal neuronal
      death following global ischemia.
AB  - Hippocampal neuronal death following transient global ischemia in the mouse takes
      days to occur, providing a potential timeframe for therapeutic intervention.
      Since matrix metalloproteinase-3 (MMP-3) enhances inflammation and tissue
      inhibitor of metalloproteinases-3 (TIMP-3) promotes apoptosis in ischemia, we
      hypothesized that they are involved in neuronal death secondary to transient
      global ischemia. Timp-3 knockout (T3KO) and wild type (T3WT) mice underwent 30
      min bilateral carotid artery occlusion (BCAO), which causes hippocampal neuronal
      death 7 days after reperfusion. Mice lacking the Timp-3 gene have significantly
      less astrocytosis, microglial reactivity, MMP-3 activity and neuronal cell death.
      In addition, T3KO mice had decreased tumor necrosis factor (TNF) receptor-1
      (TNFR1) expression and increased TNF-alpha converting enzyme (TACE) activity. Mmp
      3 KO mice with a similar BCAO showed significantly fewer microglial cells,
      reduced TNF-alpha expression, and less neuronal death than the Mmp-3 WT. To see
      if TIMP-3 and MMP-3 cell death pathways were independent, we blocked MMPs with
      the broad-spectrum MMP inhibitor, BB-94, on days 3 through 6 of reperfusion in
      T3WT and T3KO mice. BB-94 rescued hippocampal neurons at 7 days in both T3WT and
      T3KO mice, but significantly fewer neurons died in T3KO mice treated with BB-94.
      Our results indicate a novel additive role for TIMP-3 and MMP-3 in delayed
      neuronal death, and show that delayed treatment with MMP inhibitors can be used
      to reduce hippocampal death.

PMID- 19111540
TI  - Alterations in voluntary movement execution in Huntington's disease are related
      to the dominant motor system: evidence from event-related potentials.
AB  - Huntington's disease is an autosomal dominant neurogenetic disorder leading to
      striatal atrophy, characterized by involuntary movements. Voluntary movements
      also deteriorate, but the neurophysiological mechanisms are less understood. We
      investigated voluntary movement execution and its neural correlates by means of
      movement-related potentials (MRPs) in symptomatic HD (HD), presymptomatic HD
      (pHD) and controls. Reaction times (RTs) revealed hand differences in controls
      and HD, but not in pHDs. Response-locked MRPs above the contralateral primary
      motor area (M1) were similar across all groups. Yet, the HD-group showed,
      selectively for the right hand, a second contralateral (left) activation after
      the response, followed by similar activation over the ipsilateral (right) motor
      area, which is normally inhibited. Similarly parietal processes were reversed for
      right hand movements. In strong contrast, pHDs showed an increased inhibition of
      the ipsilateral hemisphere. The results suggest modulations of inhibitory
      processes in HD dependent on disease stage. Importantly, these modulations occur
      after the response and are restricted to right-hand responses, or the dominant
      motor system (left hemisphere). Since also cognitive processes preceding the MRPs
      changed, the results suggest a cognitive contribution to the emergence of
      voluntary movement dysfunction. The pattern in the pHD-group, namely an increased
      inhibition of the ipsilateral hemisphere and similar RTs between the hands
      suggest compensatory mechanisms in presymptomatic stages of the disease. Despite
      neurophysiological alterations originating in the dominant left hemisphere in
      HDs, they also affect the right hemisphere, probably due to a dysfunction in
      interhemispheric inhibition in HD.

PMID- 19111541
TI  - Treadmill training enhances the recovery of normal stepping patterns in spinal
      cord contused rats.
AB  - Treadmill training is known to improve stepping in complete spinal cord injured
      animals. Few studies have examined whether treadmill training also enhances
      locomotor recovery in animals following incomplete spinal cord injuries. In the
      present study, we compared locomotor recovery in trained and untrained rats that
      received a severe mid-thoracic contusion of the spinal cord. A robotic device was
      used to train and to test bipedal hindlimb stepping on a treadmill. Training was
      imposed for 8 weeks. The robotic device supported the weight of the rats and
      recorded ankle movements in the hindlimbs for movement analyses. Both the trained
      and untrained rats generated partial weight bearing hindlimb steps after the
      spinal cord contusion. Dragging during swing was more prevalent in the untrained
      rats than the trained rats. In addition, only the trained rats performed step
      cycle trajectories that were similar to normal step cycle trajectories in terms
      of the trajectory shape and movement velocity characteristics. In contrast,
      untrained rats executed step cycles that consisted of fast, kick-like movements
      during forward swing. These findings indicate that spinal cord contused rats can
      generate partial weight bearing stepping in the absence of treadmill training.
      The findings also suggest that the effect of treadmill training is to restore
      normal patterns of hindlimb movements following severe incomplete spinal cord
      injury in rats.

PMID- 19111543
TI  - Amblyomma americanum (L): tick macrophage migration inhibitory factor peptide
      immunization lengthens lone star tick feeding intervals in vivo.
AB  - Immunizations of New Zealand White rabbits with specific macrophage migration
      inhibitory factor (MIF) tick peptide (PEP) produced circulating anti-tick PEP
      antibodies in the hosts. Antibody titers of greater than 1:5000 to tick MIF
      peptide were observed for crude sera from PEP-immunized rabbits. PEP- and BSA
      vaccinated rabbits were infested with Amblyomma americanum adults. Feeding
      intervals, female weights, egg masses and percent egg hatch were measured for
      ticks feeding on control and immunized hosts. Feeding intervals were
      significantly lengthened to 13.3 days for PEP-vaccinated hosts compared to BSA
      vaccinated controls at 12.4 days, while female engorgement weights and egg masses
      were unchanged. By immunizing hosts using specific tick PEP, we were able to
      alter the length of time the ticks fed on their hosts.

PMID- 19111542
TI  - Neuritic dystrophy and neuronopathy in Akita (Ins2(Akita)) diabetic mouse
      sympathetic ganglia.
AB  - Diabetic autonomic neuropathy is a debilitating, poorly studied complication of
      diabetes. Our previous studies of non-obese diabetic (NOD) and related mouse
      models identified rapidly developing, dramatic pathology in prevertebral
      sympathetic ganglia; however, once diabetic, the mice did not survive for
      extended periods needed to examine the ability of therapeutic agents to correct
      established neuropathy. In the current manuscript we show that the Akita
      (Ins2(Akita)) mouse is a robust model of diabetic sympathetic autonomic
      neuropathy with unambiguous, spontaneous, rapidly-developing neuropathology which
      corresponds closely to the characteristic pathology of other rodent models and
      man. Akita mice diabetic for 2, 4 or 8 months of diabetes progressively developed
      markedly swollen axons and dendrites ("neuritic dystrophy") in the prevertebral
      superior mesenteric (SMG) and celiac ganglia (CG). Comparable changes failed to
      develop in the superior cervical ganglia (SCG) of the Akita mouse or in any
      ganglia of non-diabetic mice. Morphometric studies demonstrate an overall
      increase in presynaptic axon terminal cross sectional area, including those
      without any ultrastructural features of dystrophy. Neurons in Akita mouse
      prevertebral sympathetic ganglia show an unusual perikaryal alteration
      characterized by the accumulation of membranous aggregates and minute
      mitochondria and loss of rough endoplasmic reticulum. These changes result in the
      loss of a third of neurons in the CG over the course of 8 months of diabetes. The
      extended survival of diabetic mice and robust pathologic findings provide a
      clinically relevant paradigm that will facilitate the analysis of novel
      therapeutic agents on the reversal of autonomic neuropathy.

PMID- 19111544
TI  - BAG3 gene silencing sensitizes leukemic cells to Bortezomib-induced apoptosis.
AB  - Proteasome inhibition has emerged as a powerful option for the treatment of a
      number of malignancies including leukemias. However, Bortezomib showed limited
      single-agent activity for patients with leukemia. Here, we report for the first
      time that Bortezomib up-regulated a novel antiapoptotic protein, BAG3, in human
      leukemic cells. BAG3 gene knockdown with shRNA greatly potentiated the generation
      of apoptosis by Bortezomib in leukemia cells. Furthermore, BAG3 silencing
      enhanced the antitumor activity of Bortezomib dramatically in a nude mouse model.
      Our results indicate that knocking down BAG3 gene is a promising new approach to
      enhance the therapeutic potency of Bortezomib in leukemia.

PMID- 19111545
TI  - Down-regulation of adenine nucleotide translocase 3 and its role in camptothecin
      induced apoptosis in human hepatoma QGY7703 cells.
AB  - Adenine nucleotide translocase (ANT) is known as a core component of the
      mitochondrial permeability transition pore (MPTP) and a key player in cell death.
      However, its role in camptothecin (CPT)-induced apoptosis has not been examined.
      We showed that CPT-induced apoptosis in QGY7703 cells and down-regulated the
      expression of ANT3. Using ANT3 knock-out and overexpression experiments, we
      provide further evidence that ANT3 plays a contributive role in CPT-induced
      apoptosis through induction of MPTP. We speculate that the down-regulation of
      ANT3 upon stimulation with CPT may be part of the molecular basis underlying the
      mechanism of acquired resistance to CPT.

PMID- 19111546
TI  - Identification of a novel ubiquitin binding site of STAM1 VHS domain by NMR
      spectroscopy.
AB  - Interaction between the signal-transducing adapter molecule 1 (STAM1)
      Vps27/Hrs/Stam (VHS) domain and ubiquitin was investigated by nuclear magnetic
      resonance (NMR) spectroscopy. NMR evidence showed that the structure of STAM1 VHS
      domain resembles that of other VHS domains, especially the homologous domain of
      STAM2. We found that the VHS domain binds to ubiquitin via its hydrophobic patch
      consisting of N-terminus of helix 2 and C-terminus of helix 4 in which Trp26 on
      helix 2 plays a pivotal role in the binding. The binding between VHS and
      ubiquitin seems to be very similar to that between ubiquitin associated domain
      (UBA) and ubiquitin, however, the direction of alpha-helices involved in the
      ubiquitin binding is opposite. Here, we propose a novel ubiquitin binding site
      and the manner of ubiquitin recognition of the STAM1 VHS domain.

PMID- 19111547
TI  - The resetting of the circadian rhythm by Prostaglandin J2 is distinctly phase
      dependent.
AB  - The circadian rhythm can be reset by a variety of substances. Prostaglandin J(2)
      (PGJ(2)) is one such substance and resets the circadian rhythm in fibroblasts. In
      our current study, we examined the phase-dependent phase shift following PGJ(2)
      treatment using a real-time luciferase luminescence monitoring system. In the
      phase response curves, we observed 12h differences in the times of peaks in
      comparison with the same analysis for forskolin. Quantification of clock gene
      mRNAs following PGJ(2) administration additionally revealed a rapid decrease in
      the Per1, Rev-erbAalpha and Dbp levels. Our current findings thus suggest that
      PGJ(2) resets the peripheral circadian clock via a mechanism that is distinct
      from that used by forskolin (FK).

PMID- 19111548
TI  - Rapid and improved reconstitution of bacterial mechanosensitive ion channel
      proteins MscS and MscL into liposomes using a modified sucrose method.
AB  - The bacterial mechanosensitive (MS) channels of small (MscS) and large (MscL)
      conductance have functionally been reconstituted into giant unilamellar liposomes
      (GUVs) using an improved reconstitution method in the presence of sucrose. This
      method gives significant time savings (preparation times as little as 6h)
      compared to the classical method of protein reconstitution which uses a
      dehydration/rehydration (D/R) procedure (minimum 2 days preparation time).
      Moreover, it represents the first highly reproducible method for functional
      reconstitution of MscS as well as MscS/MscL co-reconstitution. This novel
      procedure has the potential to be used for studies of other ion channels by
      liposome reconstitution.

PMID- 19111549
TI  - IL-1 family in breast cancer: potential interplay with leptin and other
      adipocytokines.
AB  - Obesity is associated with an increased risk of breast cancer. interleukin-1 (IL
      1), a pro-inflammatory cytokine secreted by adipose tissue, is involved in breast
      cancer development. There is also convincing evidence that other adipocytokines
      including leptin not only have a role in haematopoiesis, reproduction and
      immunity but are also growth factors in cancer. Therefore, IL-1 family and leptin
      family are adipocytokines which could represent a major link between obesity and
      breast cancer progression. This minireview provides insight into recent findings
      on the prognostic significance of IL-1 and leptin in mammary tumours, and
      discusses the potential interplay between IL-1 family members and adipocyte
      derived hormones in breast cancer.

PMID- 19111550
TI  - Phosphorylated and ubiquitinated TDP-43 pathological inclusions in ALS and FTLD-U
      are recapitulated in SH-SY5Y cells.
AB  - We report phosphorylated and ubiquitinated aggregates of TAR DNA binding protein
      of 43 kDa (TDP-43) in SH-SY5Y cells similar to those in brains of amyotrophic
      lateral sclerosis (ALS) and frontotemporal lobar degeneration with ubiquitinated
      inclusions (FTLD-U). Two candidate sequences for the nuclear localization signal
      were examined. Deletion of residues 78-84 resulted in cytoplasmic localization of
      TDP-43, whereas the mutant lacking residues 187-192 localized in nuclei, forming
      unique dot-like structures. Proteasome inhibition caused these to assemble into
      phosphorylated and ubiquitinated TDP-43 aggregates. The deletion mutants lacked
      the exon skipping activity of cystic fibrosis transmembrane conductance regulator
      (CFTR) exon 9. Our results suggest that intracellular localization of TDP-43 and
      proteasomal function may be involved in inclusion formation and neurodegeneration
      in TDP-43 proteinopathies.

PMID- 19111551
TI  - Diagnosing mild enteropathy celiac disease: a randomized, controlled clinical
      study.
AB  - BACKGROUND & AIMS: The diagnostic criteria for celiac disease require small-bowel
      mucosal villous atrophy with crypt hyperplasia (Marsh III). However, mucosal
      damage develops gradually and patients may evince clinical symptoms before
      histologic changes appear. Endomysial antibodies are specific in predicting
      forthcoming villous atrophy. We hypothesized that patients with mild enteropathy
      but positive endomysial antibodies benefit from a gluten-free diet (GFD)
      similarly to patients with more severe enteropathy. METHODS: Small-bowel
      endoscopy together with clinical evaluations was performed in all together 70
      consecutive adults with positive endomysial antibodies. Of these, 23 had only
      mild enteropathy (Marsh I-II) and they were randomized either to continue on a
      gluten-containing diet or start a GFD. After 1 year, clinical, serologic, and
      histologic evaluations were repeated. A total of 47 participants had small-bowel
      mucosal lesions compatible with celiac disease (Marsh III), and these served as
      disease controls. RESULTS: In the gluten-containing diet group (Marsh I-II) the
      small-bowel mucosal villous architecture deteriorated in all participants, and
      the symptoms and abnormal antibody titers persisted. In contrast, in the GFD
      group (Marsh I-II) the symptoms were alleviated, antibody titers decreased, and
      mucosal inflammation diminished equally to celiac controls (Marsh III). When the
      trial was completed, all participants chose to continue on a life-long GFD.
      CONCLUSIONS: Patients with endomysial antibodies benefit from a GFD regardless of
      the degree of enteropathy. The diagnostic criteria for celiac disease need re
      evaluation: endomysial antibody positivity without atrophy belongs to the
      spectrum of genetic gluten intolerance, and warrants dietary treatment.

PMID- 19111552
TI  - Transgenesis approaches for functional analysis of peptidergic cells in the
      silkworm Bombyx mori.
AB  - The domestic silkworm, Bombyx mori represents an insect model of great scientific
      and economic importance. Besides the establishment of a stable germline
      transformation using the PiggyBac vector, technically feasible methods for in
      vivo gene delivery and transient gene expression were developed using viral based
      vectors, especially Sindbis viruses and baculoviruses. The recombinant
      baculovirus, Autographa californica multiple nucleopolyhedrovirus (AcMNPV),
      commonly used for large-scale protein production in permissive cell lines or
      insects, has been used for foreign gene transfer into specific peptidergic cells
      of B. mori in vivo. Since targeted gene expression is essential for functional
      analysis of neuropeptide genes and their receptors, the baculovirus-mediated gene
      transfer can serve as a reliable approach in reverse genetic studies in the
      silkworm. We review various strategies employing the baculovirus vector system
      for transient expression of molecular markers and transcription factors in
      specific peptidergic cells to investigate their roles in B. mori. We also use
      this system for functional analysis of neuropeptide signaling in the ecdysis
      behavioral sequence. Our data indicate that the AcMNPV vector is suitable for
      efficient delivery of foreign genes and their expression directed into specific
      peptidergic neurons and endocrine cells of B. mori larvae and pupae. However,
      some modifications of the vector and steps for optimization are necessary to
      minimize negative effects of viral infection on the host development. The
      transient gene expression using the AcMNPV and other virus vectors are promising
      tools for analysis of molecular mechanisms underlying various neuroendocrine
      processes during development of B. mori.

PMID- 19111553
TI  - Endothelin-1 induces connective tissue growth factor expression in
      cardiomyocytes.
AB  - Endothelin (ET)-1 is a vasoconstrictor involved in cardiovascular diseases.
      Connective tissue growth factor/CCN2 (CTGF) is a fibrotic mediator overexpressed
      in human atherosclerotic lesions, myocardial infarction, and hypertension. In
      different cell types CTGF regulates cell proliferation/apoptosis, migration, and
      extracellular matrix (ECM) accumulation and plays important roles in
      angiogenesis, chondrogenesis, osteogenesis, tissue repair, cancer and fibrosis.
      In the present study, we investigated the ET-1 signaling which triggers CTGF
      expression in cultured adult mouse atrial-muscle HL-1 cells used as a model
      system. ET-1 activated the CTGF promoter and induced CTGF expression at both mRNA
      and protein levels. Real-time PCR analysis revealed CTGF induction also in
      isolated rat heart preparations perfused with ET-1. Several intracellular signals
      elicited by ET-1 via ET receptors and even Epidermal Growth Factor Receptor
      (EGFR) contributed to the up-regulation of CTGF, including ERK activation and
      induction of the AP-1 components c-fos and c-jun, as also evaluated by ChIP
      analysis. Moreover, in cells treated with ET-1 the expression of ECM component
      decorin was abolished by CTGF silencing, indicating that CTGF is involved in ET-1
      induced ECM accumulation not only in a direct manner but also through downstream
      effectors. Collectively, our data indicate that CTGF could be a mediator of the
      profibrotic effects of ET-1 in cardiomyocytes. CTGF inhibitors should be
      considered in setting a comprehensive pharmacological approach towards ET-1
      induced cardiovascular diseases.

PMID- 19111554
TI  - Estrogen exerts concentration-dependent pro-and anti-hypertrophic effects on
      adult cultured ventricular myocytes. Role of NHE-1 in estrogen-induced
      hypertrophy.
AB  - Estrogen has been shown to protect the heart and attenuate myocardial hypertrophy
      and left ventricular remodelling through as yet to be defined mechanisms. In the
      present study we examined concentration-dependent effects of estrogen on
      hypertrophy of adult rat cardiomyocytes, potential underlying mechanisms related
      to intracellular pH (pHi) and possible sex-dependent responses. Cardiomyocytes
      were isolated from adult male and female Sprague-Dawley rats and used immediately
      for pHi determinations or cultured and subsequently treated for 24 h with 17beta
      estradiol to assess hypertrophic responses. Fluorometric measurements with the
      pHi-sensitive dye BCECF demonstrated that at 1 pM 17beta-estradiol increased pHi
      (+0.05 pH units in females and +0.12 pH units in males, P<0.05) by a rapid non
      genomic mechanism that was blocked by the sodium-hydrogen exchange isoform 1 (NHE
      1) specific inhibitor AVE-4890 (AVE, 5 microM). Treatment with 1 pM 17beta
      estradiol for 24 h increased cell size (females: 20%, P<0.05; males: 29%, P<0.05)
      and ANP expression (females: 414%, P<0.05; males: 497%, P<0.05) in a NHE-1-, and
      ERK1/2 MAPK-dependent manner. At 1 nM, 17beta-estradiol decreased pHi (females: 
      0.24 pH units, P<0.05; males: -0.07 pH units, P<0.05) which was also prevented by
      AVE, although at this concentration the hormone had no direct hypertrophic effect
      but instead prevented hypertrophy induced by phenylephrine. Our results show that
      low levels of estrogen produce cardiomyocyte hypertrophy through ERK/NHE-1
      activation and intracellular alkalinization whereas an antihypertrophic effect is
      seen at high concentrations. These effects may further our understanding of the
      role of estrogen in heart disease particularly associated with hypertrophy.

PMID- 19111555
TI  - Alternate binding modes for a ubiquitin-SH3 domain interaction studied by NMR
      spectroscopy.
AB  - Surfaces of many binding domains are plastic, enabling them to interact with
      multiple targets. An understanding of how they bind and recognize their partners
      is therefore predicated on characterizing such dynamic interfaces. Yet, these
      interfaces are difficult to study by standard biophysical techniques that often
      'freeze' out conformations or that produce data averaged over an ensemble of
      conformers. In this study, we used NMR spectroscopy to study the interaction
      between the C-terminal SH3 domain of CIN85 and ubiquitin that involves the
      'classical' binding sites of these proteins. Notably, chemical shift titration
      data of one target with another and relaxation dispersion data that report on
      millisecond time scale exchange processes are both well fit to a simple binding
      model in which free protein is in equilibrium with a single bound conformation.
      However, dissociation constants and chemical shift differences between free and
      bound states measured from both classes of experiment are in disagreement. It is
      shown that the data can be reconciled by considering three-state binding models
      involving two distinct bound conformations. By combining titration and dispersion
      data, kinetic and thermodynamic parameters of the three-state binding reaction
      are obtained along with chemical shifts for each state. A picture emerges in
      which one bound conformer has increased entropy and enthalpy relative to the
      second and chemical shifts similar to that of the free state, suggesting a less
      packed interface. This study provides an example of the interplay between entropy
      and enthalpy to fine-tune molecular interactions involving the same binding
      surfaces.

PMID- 19111556
TI  - Respiratory complexes III and IV are not essential for the assembly/stability of
      complex I in fungi.
AB  - The functional relevance of respiratory supercomplexes in various eukaryotes
      including mammals, plants, and fungi is hitherto poorly elucidated. However,
      substantial evidence indicates as a major role the assembly and/or stabilization
      of mammalian complex I by supercomplex formation with complexes III and IV. Here,
      we demonstrate by using native electrophoresis that the long-lived Podospora
      anserina mutant Cyc1-1, respiring exclusively via the alternative oxidase (AOX),
      lacks an assembled complex III and possesses complex I partially assembled with
      complex IV into a supercomplex. This resembles the situation in complex-IV
      deficient mutants displaying a corresponding phenotype but possessing I-III
      supercomplexes instead, suggesting that either complex III or complex IV is in a
      redundant manner necessary for assembly/stabilization of complex I as previously
      shown in mammals. To corroborate this notion, we constructed the double mutant
      Cyc1-1,Cox5::ble. Surprisingly, this mutant lacking both complexes III and IV is
      viable and essentially a phenocopy of mutant Cyc1-1 including the reversal of the
      phenotype towards wild-type-like characteristics by the several-fold
      overexpression of the AOX in mutant Cyc1-1,Cox5::ble(Gpd-Aox). Fungal specific
      features (not found in mammals) that must be responsible for
      assembly/stabilization of fungal complex I when complexes III and IV are absent,
      such as the presence of the AOX and complex I dimerization, are addressed and
      discussed. These intriguing results unequivocally prove that complexes III and IV
      are dispensable for assembly/stability of complex I in fungi contrary to the
      situation in mammals, thus highlighting the imperative to unravel the biogenesis
      of complex I as well as the true supramolecular organization of the respiratory
      chain and its functional significance in a variety of model eukaryotes. In
      summary, we present the first obligatorily aerobic eukaryote with an artificial,
      simultaneous lack of the respiratory complexes III and IV.

PMID- 19111557
TI  - Amyloid-beta membrane binding and permeabilization are distinct processes
      influenced separately by membrane charge and fluidity.
AB  - The 40 and 42 residue amyloid-beta (Abeta) peptides are major components of the
      proteinaceous plaques prevalent in the Alzheimer's disease-afflicted brain and
      have been shown to have an important role in instigating neuronal degeneration.
      Whereas it was previously thought that Abeta becomes cytotoxic upon forming large
      fibrillar aggregates, recent studies suggest that soluble intermediate-sized
      oligomeric species cause cell death through membrane permeabilization. The
      present study examines the interactions between Abeta40 and lipid membranes using
      liposomes as a model system to determine how changes in membrane composition
      influence the conversion of Abeta into these toxic species. Abeta40 membrane
      binding was monitored using fluorescence-based assays with a tryptophan
      substituted peptide (Abeta40 [Y10W]). We extend previous observations that
      Abeta40 interacts preferentially with negatively charged membranes, and show that
      binding of nonfibrillar, low molecular mass oligomers of Abeta40 to anionic, but
      not neutral, membranes involves insertion of the peptide into the bilayer, as
      well as sequential conformational changes corresponding to the degree of
      oligomerization induced. Significantly, while anionic membranes in the gel,
      liquid crystalline, and liquid ordered phases induce these conformational changes
      equally, membrane permeabilization is reduced dramatically as the fluidity of the
      membrane is decreased. These findings demonstrate that binding alone is not
      sufficient for membrane permeabilization, and that the latter is also highly
      dependent on the fluidity and phase of the membrane. We conclude that binding and
      pore formation are two distinct steps. The differences in Abeta behavior induced
      by membrane composition may have significant implications on the development and
      progression of AD as neuronal membrane composition is altered with age.

PMID- 19111558
TI  - Strategy abundance in 2x2 games for arbitrary mutation rates.
AB  - We study evolutionary game dynamics in a well-mixed populations of finite size,
      N. A well-mixed population means that any two individuals are equally likely to
      interact. In particular we consider the average abundances of two strategies, A
      and B, under mutation and selection. The game dynamical interaction between the
      two strategies is given by the 2x2 payoff matrix (acbd). It has previously been
      shown that A is more abundant than B, if a(N-2)+bN>cN+d(N-2). This result has
      been derived for particular stochastic processes that operate either in the limit
      of asymptotically small mutation rates or in the limit of weak selection. Here we
      show that this result holds in fact for a wide class of stochastic birth-death
      processes for arbitrary mutation rate and for any intensity of selection.

PMID- 19111559
TI  - Multi-target QPDR classification model for human breast and colon cancer-related
      proteins using star graph topological indices.
AB  - The cancer diagnostic is a complex process and, sometimes, the specific markers
      can interfere or produce negative results. Thus, new simple and fast theoretical
      models are required. One option is the complex network graphs theory that permits
      us to describe any real system, from the small molecules to the complex genetic,
      neural or social networks by transforming real properties in topological indices.
      This work converts the protein primary structure data in specific Randic's star
      networks topological indices using the new sequence to star networks (S2SNet)
      application. A set of 1054 proteins were selected from previous works and
      contains proteins related or not with two types of cancer, human breast cancer
      (HBC) and human colon cancer (HCC). The general discriminant analysis method
      generates an input-coded multi-target classification model with the
      training/predicting set accuracies of 90.0% for the forward stepwise model type.
      In addition, a protein subset was modified by single amino acid mutations with
      higher log-odds PAM250 values and tested with the new classification if can be
      related with HBC or HCC. In conclusion, we shown that, using simple input data
      such is the primary protein sequence and the simples linear analysis, it is
      possible to obtain accurate classification models that can predict if a new
      protein related with two types of cancer. These results promote the use of the
      S2SNet in clinical proteomics.

PMID- 19111560
TI  - Long run coexistence in the chemostat with multiple species.
AB  - In this work we analyze the transient behavior of the dynamics of multiple
      species competing in a chemostat for a single resource, presenting slow/fast
      characteristics. We prove that coexistence among a subset of species, with growth
      functions close to each other, can last for a substantially long time. For these
      cases, we also show that the proportion of non-dominant species can be increasing
      before decreasing, under certain conditions on the initial distribution.

PMID- 19111561
TI  - Inactivation of cholinesterase induced by non-steroidal anti-inflammatory drugs
      with horseradish peroxidase: implication for Alzheimer's disease.
AB  - AIMS: To clarify the mechanism of the protective effect of non-steroidal anti
      inflammatory drugs (NSAIDs) on Alzheimer's disease, inactivation of
      cholinesterase (ChE) induced by NSAIDs was examined. MAIN METHODS: Equine ChE and
      rat brain homogenate were incubated with NSAIDs and horseradish peroxidase (HRP)
      and H(2)O(2) (HRP-H(2)O(2)). ChE activity was measured by using 5,5'
      dithiobis(nitrobenzoic acid). By using electron spin resonance, NSAID radicals
      induced by reaction with HRP-H(2)O(2) were detected in the presence of spin trap
      agents. KEY FINDINGS: Equine ChE was inactivated by mefenamic acid with HRP
      H(2)O(2). ChE activity in rat brain homogenate decreased dependent on the
      concentration of mefenamic acid in the presence of HRP-H(2)O(2). NSAIDs
      diclofenac, indomethacin, phenylbutazone, piroxicam and salicylic acid
      inactivated ChE. Oxygen radical scavengers did not prevent inactivation of ChE
      induced by mefenamic acid with HRP-H(2)O(2). However, spin trap agents 5,5
      dimethyl-1-pyrroline-l-oxide and N-methyl-nitrosopropane, reduced glutathione and
      ascorbic acid strongly inhibited inactivation of ChE, indicating participation of
      mefenamic acid radicals. Fluorescent emission of ChE peaked at 400 nm, and the
      Vmax value of ChE changed during interaction of mefenamic acid with HRP-H(2)O(2),
      indicating that ChE may be inactivated through modification of tyrosine residues
      by mefenamic radicals. SIGNIFICANCE: The protective effect of NSAIDs on
      Alzheimer's disease seems to occur through inactivation of ChE induced by NSAIDs
      radicals.

PMID- 19111562
TI  - A missense mutation in the APC tumor suppressor gene disrupts an ASF/SF2 splicing
      enhancer motif and causes pathogenic skipping of exon 14.
AB  - A missense mutation at codon 640 in the APC gene was identified in a familial
      adenomatous polyposis (FAP) patient, however, its pathological consequence
      remained unclear. Here we found that this missense mutation interferes at the
      nucleotide level with an exonic splicing regulatory element and leads to aberrant
      splicing of the mutant APC transcript rather than exerting its effect through the
      observed amino acid change. Analysis of the patient RNA revealed complete
      skipping of exon 14 in transcripts from the mutant APC allele, leading to a
      frameshift and a premature stop codon. When cloned into a splicing reporter
      minigene and transfected into colorectal cell lines, the exon 14 point mutation
      c.1918C>G (pR640G) was found sufficient to cause the observed exon skipping.
      Bioinformatic analysis predicted the mutation to change SRp55, hnRNP A1 or
      ASF/SF2 splicing factor binding sites. Using RNA interference methodology these
      predictions were experimentally validated and revealed that only ASF/SF2 was
      required for exon 14 inclusion. These research data identify APC mutation
      c.1918C>G (pR640G) as pathogenic and indicate a mechanism involving disruption of
      an ASF/SF2 exonic splicing enhancer element. The results allow genetic diagnosis
      of a hereditary tumour predisposition but also illustrate the need to complement
      in silico prediction by splicing reporter assays.

PMID- 19111563
TI  - Mechanisms of fenthion activation in rainbow trout (Oncorhynchus mykiss)
      acclimated to hypersaline environments.
AB  - Previous studies in rainbow trout have shown that acclimation to hypersaline
      environments enhances the toxicity to thioether organophosphate and carbamate
      pesticides. In order to determine the role of biotransformation in this process,
      the metabolism of the thioether organophosphate biocide, fenthion was evaluated
      in microsomes from gills, liver and olfactory tissues in rainbow trout
      (Oncorhynchus mykiss) acclimated to freshwater and 17 per thousand salinity.
      Hypersalinity acclimation increased the formation of fenoxon and fenoxon
      sulfoxide from fenthion in liver microsomes from rainbow trout, but not in gills
      or in olfactory tissues. NADPH-dependent and independent hydrolysis was observed
      in all tissues, but only NADPH-dependent fenthion cleavage was differentially
      modulated by hypersalinity in liver (inhibited) and gills (induced). Enantiomers
      of fenthion sulfoxide (65% and 35% R- and S-fenthion sulfoxide, respectively)
      were formed in liver and gills. The predominant pathway of fenthion activation in
      freshwater appears to be initiated through initial formation of fenoxon which may
      be subsequently converted to the most toxic metabolite fenoxon R-sulfoxide.
      However, in hypersaline conditions both fenoxon and fenthion sulfoxide formation
      may precede fenoxon sulfoxide formation. Stereochemical evaluation of sulfoxide
      formation, cytochrome P450 inhibition studies with ketoconazole and immunoblots
      indicated that CYP3A27 was primarily involved in the enhancement of fenthion
      activation in hypersaline-acclimated fish with limited contribution of FMO to
      initial sulfoxidation.

PMID- 19111564
TI  - Contribution of liver mitochondrial membrane-bound glutathione transferase to
      mitochondrial permeability transition pores.
AB  - We recently reported that the glutathione transferase in rat liver mitochondrial
      membranes (mtMGST1) is activated by S-glutathionylation and the activated mtMGST1
      contributes to the mitochondrial permeability transition (MPT) pore and
      cytochrome c release from mitochondria [Lee, K.K., Shimoji, M., Quazi, S.H.,
      Sunakawa, H., Aniya, Y., 2008. Novel function of glutathione transferase in rat
      liver mitochondrial membrane: role for cytochrome c release from mitochondria.
      Toxcol. Appl. Pharmacol. 232, 109-118]. In the present study we investigated the
      effect of reactive oxygen species (ROS), generator gallic acid (GA) and GST
      inhibitors on mtMGST1 and the MPT. When rat liver mitochondria were incubated
      with GA, mtMGST1 activity was increased to about 3 fold and the increase was
      inhibited with antioxidant enzymes and singlet oxygen quenchers including 1,4
      diazabicyclo [2,2,2] octane (DABCO). GA-mediated mtMGST1 activation was prevented
      by GST inhibitors such as tannic acid, hematin, and cibacron blue and also by
      cyclosporin A (CsA). In addition, GA induced the mitochondrial swelling which was
      also inhibited by GST inhibitors, but not by MPT inhibitors CsA, ADP, and
      bongkrekic acid. GA also released cytochrome c from the mitochondria which was
      inhibited completely by DABCO, moderately by GST inhibitors, and somewhat by CsA.
      Ca(2+)-mediated mitochondrial swelling and cytochrome c release were inhibited by
      MPT inhibitors but not by GST inhibitors. When the outer mitochondrial membrane
      was isolated after treatment of mitochondria with GA, mtMGST1 activity was
      markedly increased and oligomer/aggregate of mtMGST1 was observed. These results
      indicate that mtMGST1 in the outer mitochondrial membrane is activated by GA
      through thiol oxidation leading to protein oligomerization/aggregation, which may
      contribute to the formation of ROS-mediated, CsA-insensitive MPT pore, suggesting
      a novel mechanism for regulation of the MPT by mtMGST1.

PMID- 19111565
TI  - Translocation of botulinum neurotoxin light chain protease by the heavy chain
      protein-conducting channel.
AB  - Clostridial botulinum neurotoxins (BoNTs) inhibit synaptic exocytosis;
      intoxication requires the di-chain protein to undergo conformational changes in
      response to pH and redox gradients across the endosomal membrane with consequent
      formation of a protein-conducting channel by the heavy chain (HC) that
      translocates the light chain (LC) protease into the cytosol, colocalizing it with
      the substrate SNARE proteins. We investigate the dynamics of protein
      translocation across membranes using a sensitive single-molecule assay to track
      translocation events with millisecond resolution on lipid bilayers and on
      membrane patches of Neuro 2A cells. Translocation of BoNT/A LC by the HC is
      observed in real time as changes of channel conductance: the channel is occluded
      by the light chain during transit, and open after completion of translocation and
      release of cargo, acting intriguingly similar to the protein
      conducting/translocating channels of the endoplasmic reticulum, mitochondria, and
      chloroplasts. Our findings support the notion of an interdependent, tight
      interplay between the HC transmembrane chaperone and the LC cargo that prevents
      LC aggregation and dictates the productive passage of cargo through the channel
      and completion of translocation. The protein-conducting channel of BoNT, a key
      element in the process of neurotoxicity, emerges therefore as a target for
      antidote discovery - a novel paradigm of paramount significance to health science
      and biodefense.

PMID- 19111566
TI  - Different mechanisms of inhibition of nerve terminals by botulinum and snake
      presynaptic neurotoxins.
AB  - The different mode of action on peripheral nerve terminals of the botulinum
      neurotoxins and of the snake presynaptic phospholipase A2 neurotoxins is reviewed
      here. These two groups of toxins are highly toxic because they are neurospecific
      and at the same time are enzymes that can modify many substrate molecules before
      being inactivated. The similarity of symptoms they cause in humans derives from
      the fact that both botulinum neurotoxins (seven serotypes named A-G) and snake
      presynaptic PLA2 neurotoxins block the nerve terminals and that peripheral
      cholinergic terminals are major targets. Given this general similarity of targets
      and clinical symptoms, the specific molecular and cellular mechanisms at the
      basis of their action are very different. This difference appears evident from
      the beginning of intoxication, i.e. neurotoxins binding to peripheral nerve
      terminals and proceeds with the different site of actions and molecular targets.

PMID- 19111567
TI  - Purification and characterization of a novel lectin from the toxic wild mushroom
      Inocybe umbrinella.
AB  - From the dried fruiting bodies of the toxic mushroom Inocybe umbrinella, a novel
      lectin with a molecular mass of 17 kDa has been isolated with about 160-fold
      purification. The purification protocol comprised ion exchange chromatography on
      DEAE-cellulose, and CM-cellulose, and gel filtration on Superdex 75. Among the
      carbohydrates tested, raffinose, d-melibiose, alpha-lactose and d(+)-galactose
      could inhibit the hemagglutinating activity of the lectin. The hemagglutinating
      activity was stable between 10 and 60 degrees C, in 12.5-100mM HCl, and in 50mM
      NaOH. The hemagglutinating activity was inhibited by Ca(2+), Mn(2+)and Mg(2+)
      ions, but was unaffected by Fe(3+), Zn(2+) and Al(3+) ions. The lectin inhibited
      HIV-1 reverse transcriptase with an IC(50) of 4.7+/-0.2 microM. Proliferation of
      tumor cells including hepatoma HepG2 cells and breast cancer MCF7 cells was
      inhibited by the lectin with an IC(50) of 3.5+/-0.2 microM and 7.4+/-0.3 micoM,
      respectively. The lectin has a unique N-terminal amino acid sequence, DGVLATNAVA.
      It did not exhibit antifungal activity. The present report is the first on an
      Inocybe lectin and represents one of the very few reports on lectins from toxic
      mushrooms.

PMID- 19111568
TI  - A comparison of 1-benzylpiperazine and methamphetamine in their acute effects on
      anxiety-related behavior of hooded rats.
AB  - Following i.p. treatment with saline, 10 or 20 mg/kg 1-benzylpiperazine, or 1 or
      2 mg/kg methamphetamine, hooded rats were observed in an open field, a light-dark
      box and (24 h after exposure to the drugs) a Y maze with one novel and one
      familiar arm. Both drugs increased open-field rearing and ambulation, but only
      methamphetamine increased and decreased respectively occupancy of center squares
      and corners, while stereotyped head movements were increased by 20 mg/kg
      benzylpiperazine. Time spent in and entries of the light compartment of the light
      dark box were decreased by benzylpiperazine but not methamphetamine, and entries
      of the novel Y-maze arm were decreased by methamphetamine for male rats only.
      Although most behavior emitted in the open field and light-dark box following
      treatment with methamphetamine could be ascribed to the drug's locomotor
      stimulant effect, increased stereotypy with the high dose probably interfered
      with this action for benzylpiperazine. However, both drugs may have led to some
      anxiety-related novelty avoidance in the Y maze. Overall, the patterns of results
      for the two drugs revealed more similarities than differences (with
      methamphetamine possibly being more effective than benzylpiperazine) and thus
      supported the view that, because of commonalities in their neurochemical effects,
      benzylpiperazine may have similar abuse and dependence risks to methamphetamine.

PMID- 19111569
TI  - Cardiovascular benefits of smoking regulations: The effect of decreased exposure
      to passive smoking.
AB  - OBJECTIVES: Decreases in population rates of acute myocardial infarction (AMI)
      have been repeatedly seen in the first months after the introduction of
      regulations banning smoking in public places. By decreasing the exposure to
      passive smoking and its acute cardiovascular effects, smoking regulations may
      cause an immediate drop in AMI incidence, beginning from the initial days after
      their introduction. Using simulations, we quantified this expected decrease.
      METHODS: Expected AMI decreases were estimated using several parameters,
      including prevalence of exposure to passive and active smoking, relative risks of
      AMI associated with active and passive smoking, decrease in exposure to passive
      smoking after the introduction of the regulation, and level of susceptibility of
      active smokers to exposure to passive smoking. RESULTS: After evaluating several
      possible combinations of these parameters, we found that AMI reductions of 5-15%
      seem likely. For example, a scenario with a population average of 5 hours per
      week of overall exposure to passive smoking, a 50% reduction in this exposure
      after the introduction of the regulation, an acute relative risk (RR) of AMI of
      4.5 in the first hour after passive smoking exposure, and similar susceptibility
      to passive smoking among both active and passive smokers translates into a 8.6%
      decrease in AMI. CONCLUSIONS: Smoking regulations can cause immediate and
      relevant decreases in AMI through the prevention of exposure to passive smoking.

PMID- 19111571
TI  - Allergen-related approaches to immunotherapy.
AB  - Allergic diseases, including asthma, rhinitis and eczema, represent a major
      health burden worldwide. Mainstay treatments are allergen avoidance where
      feasible and pharmacotherapy for symptom relief. For selected patients, allergen
      specific immunotherapy (SIT) offers the prospect of long lasting clinical
      efficacy. SIT involves the administration of allergen extract using a
      standardized regimen, usually subcutaneously or increasingly sublingually.
      However, application of this potentially curative treatment is restricted,
      largely due to the risk of serious adverse events, especially in asthmatics and
      for potent allergens such as peanut, seafood and latex. New insights into
      immunological mechanisms underlying effective SIT and molecular characterization
      of allergens and their recognition by the immune system suggest strategies for
      refinement of SIT. Selective targeting of allergen-specific T cells, especially
      regulatory T cells, is likely to be pivotal for efficacy. Recombinant allergens
      lacking IgE reactivity and small T cell epitope-based peptides are being trialled
      clinically with evidence of efficacy without serious IgE-mediated adverse
      reactions. Adjuvants, either co-administered or incorporated into a recombinant
      allergen vaccine to target tolerogenic dendritic cells may also increase
      efficacy. The safer sublingual route of allergen administration is attracting
      interest and different allergen forms may be optimal for inducing tolerance by
      this route. Defined allergen-derived molecules or peptides offer ease of
      standardization and, coupled with appropriate targeting of immunoregulatory
      mechanisms, will result in more widespread clinical use of SIT. Adjunct therapies
      such as anti-IgE antibody and corticosteroids may minimize the likelihood of
      adverse reactions in those with severe allergic disease who would most benefit
      from this treatment.

PMID- 19111572
TI  - Cajal's second great battle for the neuron doctrine: the nature and function of
      neurofibrils.
AB  - One hundred years ago, a novel kind of reticularism threatened to displace the
      neuron doctrine as the established model of functional organization of the
      nervous system. The challenging paradigm, championed by Stephan von Apathy and
      Albrecht Bethe, held that nerve impulses propagate along neurofibrils connected
      in a continuous network throughout all nerve cells. Santiago Ramon y Cajal, a
      leading figure in the conception of the neuron doctrine, headed again the battle
      against this return of reticularism. Dissatisfied with the available staining
      techniques, he devised the "reduced silver nitrate method" that even Camillo
      Golgi recognized as the best at the time for revealing the neurofibrils. In 1904
      Cajal already published over a dozen papers in three languages describing
      neurofibril distributions in the nervous systems of diverse vertebrates and
      invertebrates, under both normal and experimental conditions. Next he
      investigated the involvement of neurofibrils in the process of nerve
      regeneration. This unprecedented survey led him to the conclusion that the
      neurofibrils are linear "colonies" of particles constituting a semi-solid,
      dynamic internal skeleton of the nerve cell. Apathy reacted with a long invective
      paper that Cajal had no choice but acknowledging. His comprehensive reply,
      published in 1908, meant the effective end of the renewed reticularist campaign
      against the neuron doctrine. Along the way, a visionary and today almost
      forgotten chapter in the history of the cytoskeleton had also been written.

PMID- 19111570
TI  - Stress-induced prefrontal reorganization and executive dysfunction in rodents.
AB  - The prefrontal cortex (PFC) mediates a range of higher order 'executive
      functions' that subserve the selection and processing of information in such a
      way that behavior can be planned, controlled and directed according to shifting
      environmental demands. Impairment of executive functions typifies many forms of
      psychopathology, including schizophrenia, mood and anxiety disorders and
      addiction, that are often associated with a history of trauma and stress. Recent
      research in animal models demonstrates that exposure to even brief periods of
      intense stress is sufficient to cause significant structural remodeling of the
      principle projection neurons within the rodent PFC. In parallel, there is growing
      evidence that stress-induced alterations in PFC neuronal morphology are
      associated with deficits in rodent executive functions such as working memory,
      attentional set-shifting and cognitive flexibility, as well as emotional
      dysregulation in the form of impaired fear extinction. Although the molecular
      basis of stress-induced changes in PFC morphology and function are only now being
      elucidated, an understanding of these mechanisms could provide important insight
      into the pathophysiology of executive dysfunction in neuropsychiatric disease and
      foster improved strategies for treatment.

PMID- 19111574
TI  - The role of FoxP3+CD4+CD25hi Tregs in the pathogenesis of myasthenia gravis.
AB  - CD4(+)CD25(+) regulatory T cells (CD4(+)CD25(+) Tregs) play a critical role in
      the maintenance of peripheral self-tolerance and the regulation of immune
      responses. Genetic defects that primarily affect the development and/or function
      of CD4(+)CD25(+) Tregs result in severe autoimmune diseases and inflammatory
      disorders. In this study, we investigated whether the peripheral pool and the
      function of CD4(+)CD25(+) Tregs are altered in patients of myasthenia gravis
      (MG), a chronic autoimmune disorder that results in progressive skeletal muscle
      weakness. Here we showed that both mRNA and protein expression level of FoxP3 in
      CD4(+)CD25(+) Tregs are dramatically down-regulated, accompanied by an severe
      functional defect in CD4(+)CD25(+) Tregs regulatory activity when cocultured with
      autologous CD4(+)CD25(-) T cells, although the reservoir of CD4(+)CD25(+) Tregs
      is not changed in peripheral blood from MG patients. Since FoxP3 is a pivotal
      transcription factor that indispensable for the generation and the regulatory
      function of CD4(+)CD25(+) Tregs, our data suggested that the functional activity
      of CD4(+)CD25(+) Tregs is inhibited in MG patients and that MG might originate
      from the dysfunction of CD4(+)CD25(+) Tregs. Although the underlying molecular
      basis for the reduced expression of FoxP3 in CD4(+)CD25(+) Tregs from MG patients
      remains unknown, this study provided a potential target for MG therapy.

PMID- 19111573
TI  - A mimotope gene encoding the major IgE epitope of allergen Phl p 5 for epitope
      specific immunization.
AB  - A gene vaccine based on a mammalian expression vector containing the sequence of
      a peptide mimotope of Phl p 5 was constructed. To test whether mimotope gene
      vaccines can induce allergen-specific antibody responses via molecular mimicry,
      BALB/c mice were immunized using the mimotope construct with or without a tetanus
      toxin T-helper epitope. Moreover, intradermal injection was compared to epidermal
      application via gene gun immunization. Immunization with both mimotope gene
      constructs elicited allergen-specific antibody responses. As expected, gene gun
      bombardment induced a Th2-biased immune response, typically associated with IgG1
      and IgE antibody production. In contrast, intradermal injection of the vaccine
      triggered IgG2a antibody expression without any detectable IgE levels, thus
      biasing the immune response towards Th1. In an RBL assay, mimotope-specific IgG
      antibodies were able to prevent cross-linking of allergen-specific IgE by Phl p
      5. A construct coding for the complete Phl p 5 induced T-cell activation, IFN
      gamma and IL-4 production. In contrast, the mimotope-DNA construct being devoid
      of allergen-specific T-cell epitopes had no capacity to activate allergen
      specific T cells. Taken together, our data show that it is feasible to induce
      blocking IgG antibodies with a mimotope-DNA construct when applied intradermally.
      Thus the mimotope-DNA strategy has two advantages: (1) the avoidance of IgE
      induction and (2) the avoidance of triggering allergen-specific T-lymphocytes. We
      therefore suggest that mimotope gene vaccines are potential candidates for
      epitope-specific immunotherapy of type I allergy.

PMID- 19111575
TI  - Enhancement of ovalbumin-induced pulmonary eosinophilia by intranasal
      administration of alpha1-proteinase inhibitor type 2 antisense oligonucleotides.
AB  - To identify asthma-susceptibility genes, we did proteome analyses of the lung
      from control and ovalbumin-sensitized BALB/c mice. Among the 6 up-regulated
      proteins is alpha(1)-protease inhibitor (alpha(1)-PI) type 2, which is a member
      of the serine protease inhibitor superfamily of protease inhibitors that
      participate in a variety of physiological functions, including extracellular
      matrix remodeling and inflammation. The up-regulated expression of alpha(1)-PI
      type 2 was confirmed by real-time PCR. Then we examined mRNA expression of five
      members of the alpha(1)-PI family genes (alpha(1)-PI types 1-5) in several organs
      of BALB/c mice and found that in addition to the liver, all the organs tested
      also expressed different isoforms of alpha(1)-PI in a tissue-specific manner,
      albeit to a lesser extent compared with the liver. When a similar study was
      performed with C57BL/6 mice, which have been shown to be more susceptible to
      ovalbumin-induced asthma than BALB/c mice, a pair of remarkable differences
      between the mouse strains were revealed: (1) the magnitude of alpha(1)-PI type 2
      mRNA in all the organs was much higher in BALB/c than in C57BL/6 mice and (2)
      alpha(1)-PI type 2 is the only isoform expressed in the lung of BALB/c, but not
      of C57BL/c mice. Using the antisense oligonucleotide technology to specifically
      down-regulate expression of alpha(1)-PI type 2, we demonstrated that pulmonary
      infiltration of eosinophils was significantly increased by intranasal
      administration of alpha(1)-PI type 2 antisense oligonucleotides in OVA-sensitized
      mice, suggesting that alpha(1)-PI type 2 may suppress the progress of asthma,
      probably by acting on neutrophil elastase, which can produce many of the
      pathological features of asthma.

PMID- 19111577
TI  - Induction of mitotic S-phase of host and neighboring cells by Toxoplasma gondii
      enhances parasite invasion.
AB  - The intracellular parasite Toxoplasma gondii extensively modifies its host cell
      so as to efficiently grow and divide. Among these cellular changes, T. gondii
      alters the cell cycle of host cells it has invaded. We found that T. gondii
      affects the cell cycle of not only the cells it directly invades, but neighboring
      cells as well. Both direct invasion by T. gondii and exposure to filtered medium
      from cultures of T. gondii-infected cells (conditioned medium) caused normally
      quiescent fibroblasts to enter S-phase. T. gondii has been shown to attach to and
      invade S-phase host cells more readily, and we found that conditioned medium
      increased the rate of invasion of T. gondii into new host cells. Thus it appears
      that T. gondii directly releases, or induces parasitized host cells to release, a
      factor that induces neighboring cells to enter S-phase, allowing more rapid
      invasion by extracellular T. gondii and providing a possible selective advantage
      for the parasite.

PMID- 19111576
TI  - The cathepsin L of Toxoplasma gondii (TgCPL) and its endogenous macromolecular
      inhibitor, toxostatin.
AB  - Toxoplasma gondii is an obligate intracellular parasite of all vertebrates,
      including man. Successful invasion and replication requires the synchronized
      release of parasite proteins, many of which require proteolytic processing.
      Unlike most parasites, T. gondii has a limited number of Clan CA, family C1
      cysteine proteinases with one cathepsin B (TgCPB), one cathepsin L (TgCPL) and
      three cathepsin Cs (TgCPC1, 2, 3). Previously, we characterized toxopain, the
      only cathepsin B enzyme, which localizes to the rhoptry organelle. Two cathepsin
      Cs are trafficked through dense granules to the parasitophorous vacuole where
      they degrade peptides. We now report the cloning, expression, and modeling of the
      sole cathepsin L gene and the identification of two new endogenous inhibitors.
      TgCPL differs from human cathepsin L with a pH optimum of 6.5 and its substrate
      preference for leucine (vs. phenylalanine) in the P2 position. This distinct
      preference is explained by homology modeling, which reveals a non-canonical
      aspartic acid (Asp 216) at the base of the predicted active site S2 pocket, which
      limits substrate access. To further our understanding of the regulation of
      cathepsins in T. gondii, we identified two genes encoding endogenous cysteine
      proteinase inhibitors (ICPs or toxostatins), which are active against both TgCPB
      and TgCPL in the nanomolar range. Over expression of toxostatin-1 significantly
      decreased overall cysteine proteinase activity in parasite lysates, but had no
      detectable effect on invasion or intracellular multiplication. These findings
      provide important insights into the proteolytic cascades of T. gondii and their
      endogenous control.

PMID- 19111578
TI  - Presenilin-dependent expression of STIM proteins and dysregulation of
      capacitative Ca2+ entry in familial Alzheimer's disease.
AB  - Mutations in presenilin 1 (PS1), which are the major cause of familial
      Alzheimer's disease (FAD), are involved in perturbations of cellular Ca2+
      homeostasis. Attenuation of capacitative Ca2+ entry (CCE) is the most often
      observed alteration of Ca2+ homeostasis in cells bearing FAD PS1 mutations.
      However, molecular mechanisms underlying this CCE impairment remains elusive. We
      demonstrate that cellular levels of STIM1 and STIM2 proteins, which are key
      players in CCE, depend on presenilins. We found increased level of STIM1 and
      decreased level of STIM2 proteins in mouse embryonic fibroblasts lacking
      presenilins. Fura-2 ratiometric assays revealed that CCE is enhanced in these
      cells after Ca2+ stores depletion by thapsigargin treatment. In turn,
      overexpression of PS1 with FAD mutations in HEK293 cells led to an attenuation of
      CCE. Although, no changes in STIM protein levels were observed in these HEK293
      cells, FAD mutations in endogenous PS1 in human B lymphocytes resulted in a
      decreased expression of STIM2 in parallel to an attenuation of CCE. Our
      experiments showing that knock-out of presenilins in MEF cells and FAD mutations
      in endogenous PS1 in lymphocytes affect both CCE and the cellular level of STIM
      proteins open new perspectives for studies on CCE in FAD.

PMID- 19111579
TI  - Bimodal modulation of tau protein phosphorylation and conformation by
      extracellular Zn2+ in human-tau transfected cells.
AB  - Abnormal homeostasis of heavy metals is a well-documented physiopathological
      mechanism in Alzheimer's disease. An exacerbation of these abnormalities is best
      illustrated in the amyloid plaques in Alzheimer's disease brain tissue, in which
      zinc reaches the enormous concentration of 1000 microM. Zinc in the plaques is
      thought to originate from impaired glutamatergic neurons distributed in the
      associative cortex and limbic structures of normal brain. Although the
      characteristics of zinc binding to Abeta and its role in promotion of Abeta
      aggregation have been intensively studied, the contribution of zinc to the
      development of tau pathology remains elusive. To further document the effect of
      zinc we have investigated the modifications of tau phosphorylation, conformation
      and association to microtubules induced by zinc in clonal cell lines expressing a
      human tau isoform. A bimodal dose dependent effect of zinc was observed. At 100
      microM zinc induced a tau dephosphorylation on the PHF-1 epitope, and at higher
      zinc concentrations induced the appearance of the abnormal tau conformational
      epitope MC1 and reduced the electrophoretic mobility of tau, known to be
      associated to increased tau phosphorylation. High zinc concentrations also
      increased glycogen synthase kinase-3beta (GSK-3beta) phosphorylation on tyrosine
      216, a phosphorylation associated with increased activity of this tau kinase.
      Live imaging of tau-EGFP expressing cells demonstrated that high zinc
      concentrations induced a release of tau from microtubules. These results suggest
      that zinc plays a significant role in the development of tau pathology associated
      to Alzheimer's disease.

PMID- 19111581
TI  - Lysosomal disorders: from storage to cellular damage.
AB  - Lysosomal storage diseases represent a group of about 50 genetic disorders caused
      by deficiencies of lysosomal and non-lysosomal proteins. Patients accumulate
      compounds which are normally degraded in the lysosome. In many diseases this
      accumulation affects various organs leading to severe symptoms and premature
      death. The revelation of the mechanism by which stored compounds affect cellular
      function is the basis for understanding pathophysiology underlying lysosomal
      storage diseases. In the past years it has become clear that storage compounds
      interfere with various processes on the cellular level. The spectrum covers e.g.
      receptor activation by non-physiologic ligands, modulation of receptor response
      and intracellular effectors of signal transduction cascades, impairment of
      autophagy, and others. Importantly, many of these processes are associated with
      accumulation of storage material in non-lysosomal compartments. Here we summarize
      current knowledge on the effects that storage material can elicit on the cellular
      level.

PMID- 19111580
TI  - Secondary lipid accumulation in lysosomal disease.
AB  - Lysosomal diseases are inherited metabolic disorders caused by defects in a wide
      spectrum of lysosomal and a few non-lysosomal proteins. In most cases a single
      type of primary storage material is identified, which has been used to name and
      classify the disorders: hence the terms sphingolipidoses, gangliosidoses,
      mucopolysaccharidoses, glycoproteinoses, and so forth. In addition to this
      primary storage, however, a host of secondary storage products can also be
      identified, more often than not having no direct link to the primary protein
      defect. Lipids - glycosphingolipids and phospholipids, as well as cholesterol -
      are the most ubiquitous and best studied of these secondary storage materials.
      While in the past typically considered nonspecific and nonconsequential features
      of these diseases, newer studies suggest direct links between secondary storage
      and disease pathogenesis and support the view that understanding all aspects of
      this sequestration process will provide important insights into the cell biology
      and treatment of lysosomal disease.

PMID- 19111582
TI  - Generation and characterization of a novel, permanently active S100P mutant.
AB  - S100 proteins function as Ca2+ signal transducers by regulating cellular targets
      in their Ca2+ bound conformation. S100P is a member of the S100 protein family
      that can activate the membrane and F-actin binding protein ezrin in a Ca2+
      dependent manner at least in vitro. Here we generated a novel tool to elucidate
      directly the S100P-ezrin interaction in vivo. This was achieved by constructing a
      S100P derivative that contained mutations in the two EF hand loops predicted to
      lock the protein in a permanently active state. The resulting S100P mutant,
      termed here S100P pa, could be purified as a soluble protein and showed
      biochemical properties displayed by wild-type S100P only in the presence of Ca2+.
      Importantly, S100P pa bound to the N-terminal domain of ezrin in the absence of
      Ca2+ showing an affinity only slightly reduced as compared to that of Ca2+-bound
      WT S100P. In line with this permanent complex formation, S100P pa colocalized
      with ezrin to plasma membrane protrusions of epithelial cells even in the absence
      of intracellular Ca2+ transients. Thus, S100P pa is a novel type of S100 protein
      mutant locked in a permanently active state that shows an unregulated complex
      formation with its cellular target ezrin.

PMID- 19111583
TI  - Comparison of rose bengal-chloramphenicol and modified aureomycin-rose bengal
      glucose-peptone agar as media for the enumeration of molds and yeasts in water by
      membrane filtration techniques.
AB  - The present study compares the suitability of rose bengalchloramphenicol (RBCh)
      and modified aureomycin-rose bengal glucose-peptone agar for enumerating fungi
      recovered from diverse water sources using the membrane filtration method. Both
      mold and yeast colonies were established more rapidly, with more intensified
      colony colors and higher RBCh counts.

PMID- 19111584
TI  - Modulation of CD163 receptor expression and replication of porcine reproductive
      and respiratory syndrome virus in porcine macrophages.
AB  - Porcine reproductive and respiratory syndrome virus (PRRSV) has a specific cell
      tropism for differentiated macrophages, such as porcine alveolar macrophages
      (PAMs). We analyzed the expression of CD163 on PAMs and macrophages derived from
      CD14 positive blood monocytes (MDMs), in correlation with PRRSV replication. By
      flow cytometry analysis, we showed that the levels of CD163 expression correlated
      well with the overall level of PRRSV replication. We further examined the effects
      of modulators of macrophage function, including 12-O-tetradecanoylphorbol-13
      acetate (TPA), lipopolysaccharide (LPS), and interleukin (IL)-10 on the
      expression of CD163 and PRRSV replication. Pre-treatment of PAMs or MDMs with TPA
      or LPS resulted in decreased expression of CD163 and reduction in PRRSV
      replication. On the contrary, the incubation of CD14 positive monocytes with IL
      10 during differentiation into MDMs resulted in up-regulated expression of CD163
      with a corresponding increase in PRRSV infection. These data indicate that the
      expression of CD163 on macrophages in different microenvironments, in vivo, may
      determine the replication efficiency and subsequent pathogenecity of PRRSV.

PMID- 19111586
TI  - Structure-activity relationships of novel peptide agonists of the human
      bradykinin B2 receptor.
AB  - The nonapeptide bradykinin (BK) is involved in the genesis of inflammation, edema
      and in pain mediation. As such, much effort has gone into the development of
      peptide/non-peptide antagonists to counteract these processes. However, there is
      an increasing awareness of the potential value of chemically stable BK agonists
      in the treatment of diabetes and cardiovascular diseases. In this study, a
      structure-activity relationship study of BK was performed to develop potent and
      stable peptide mimetics active at the human B2 receptors (hB2R). Twenty-three
      analogues were produced with substitutions at positions 1, 3, 5, 7, 8 and/or 9 of
      BK. In vitro binding (on transiently transfected HEK-293T cells) and biological
      activities (vasomotricity tests on human umbilical veins, MAPK assays on HEK-293T
      cells) of novel BK peptide derivatives at hB2R were determined alongside with
      previously reported synthetic agonists (e.g. RMP-7, JMV1609, FR190997). Some
      peptides were also tested in vivo in rats and rabbits using blood pressure
      assays. Two compounds, [Hyp(3), Thi(5), Cha(8)]-BK and [Hyp(3), Thi(5),
      (N)Chg(7), Thi(8)]-BK, exhibited equivalent (or even greater) in vitro affinities
      and potencies to BK at the naturally expressed and recombinant hB2R. Their
      potency and duration of action in vivo were highly superior to BK, thus inferring
      that they can withstand intravascular proteolysis. These novel compounds show
      promise as candidates for investigating the pharmacology of BK receptors and
      developing potential therapeutical applications.

PMID- 19111585
TI  - Vertical transmission of tick-borne encephalitis virus between generations of
      adapted reservoir small rodents.
AB  - Vertical transmission of tick-borne encephalitis virus (TBEV) between generations
      of the small rodents-red voles Myodes rutilus Pallas (previously known as
      Clethrionomys rutilus Pallas) was shown for naturally infected reservoir hosts
      and after experimental infection with different sublethal doses of the viral
      strains. For wild red voles and for their progeny born in 240-280 days after
      experimental infection of their parents the TBEV was detected in up to 90% of
      samples by RT-PCR, ELISA and bioassays. Small amounts of the TBEV RNA found in
      embryos, placenta and blood cells could serve as evidence of prenatal
      transmission. Postnatal transfer of the virus might occur through the rodent
      milk. Analysis of the TBEV E gene nucleotide sequences of RT-PCR products
      revealed missense mutations resulting in amino acid substitution K280Q in newborn
      red vole in comparison with its parent female. Taken together, the data confirmed
      the TBEV vertical transmission among generations of its adapted mammal reservoir
      hosts. The virus transfer might occur before, during and/or after birth of the
      small rodents with high frequencies. In the wild it could provide the TBEV long
      term persistence in mammal hosts without an (any) involvement of arthropod
      vectors thus selecting dangerous mammal-adapted variants.

PMID- 19111587
TI  - Identification and structural insights of three novel antimicrobial peptides
      isolated from green coconut water.
AB  - Infections caused by pathogenic bacteria could cause an expressive negative
      impact on human health. A significant enhance in resistance to commercial
      antibiotics has been observed in all kinds of pathogenic bacteria. In order to
      find novel approaches to control such common infections, a wide number of defense
      peptides with bactericidal properties have been characterized. In this report,
      three peptides lower than 3kDa were purified and identified from green coconut
      (Cocos nucifera L.) water by using reversed phase-high performance liquid
      chromatography (HPLC), showing molecular masses of 858Da, 1249Da and 950Da. First
      one, named Cn-AMP1, was extremely efficient against both Gram-positive and Gram
      negative bacteria, being MICs calculated for three peptides. All complete
      sequences were determined by MALDI-ToF analysis showing no identity in databanks.
      Moreover, peptide net charge and hydrophobicity of each peptide was in silico
      evaluated. Finally molecular modeling and dynamics were also applied generating
      peptides three-dimensional structures, indicating a better explanation to
      probable mechanisms of action. Cn-AMPs here reported show remarkable potential to
      contribute in the development of novel antibiotics from natural sources.

PMID- 19111588
TI  - Nicotinic receptor agonists and antagonists increase sAPPalpha secretion and
      decrease Abeta levels in vitro.
AB  - We have earlier reported that Abeta were significantly reduced in brains of
      smoking Alzheimer patients and control subjects compared with non-smokers, as
      well as in nicotine treated APPsw transgenic mice. To examine the mechanisms by
      which nicotine modulates APP processing we here measured levels of secreted
      amyloid precursor protein (sAPPalpha), total sAPP, Abeta40 and Abeta42 in
      different cell lines expressing different nicotinic receptor (nAChR) subtypes or
      no nAChRs. Treatment with nicotine increased release of sAPPalpha and at the same
      time lowered Abeta levels in both SH-SY5Y and SH-SY5Y/APPsw cells expressing
      alpha3 and alpha7 nAChR subtypes. These effects could also be evoked by co
      treatment with the competitive alpha7 nAChR antagonists alpha-bungarotoxin and
      methyllycaconitine (MLA), and by these antagonists alone, suggesting that binding
      to the agonist binding site, rather than activation of the receptor, may be
      sufficient to trigger changes in APP processing. The nicotine-induced increase in
      sAPPalpha could only be blocked by co-treatment with the open channel blocker
      mecamylamine. In addition to nicotine, the agonists epibatidine and cytisine both
      significantly increased the release of sAPP in M10 cells expressing the
      alpha4/beta2 nAChR subtype, and this effect was blocked by co-treatment with
      mecamylamine but not by the alpha4/beta2 competitive antagonist dihydro-beta
      erythroidine. The lack of effect of nicotine on sAPPalpha and Abeta levels in HEK
      293/APPsw cells, which do not express any nAChRs, demonstrates that the nicotine
      induced attenuation of beta-amyloidosis is mediated by nAChRs and not by a direct
      effect of nicotine. Our data show that nicotinic compounds stimulate the non
      amyloidogenic pathway and that alpha4 and alpha7 nAChRs play a major role in
      modulating this process. Nicotinic drugs directed towards specific nAChR subtypes
      might therefore be beneficial for the treatment of AD not only by lowering Abeta
      production but also by enhance release of neuroprotective sAPPalpha.

PMID- 19111589
TI  - Profiling of BoNT/C3-reversible gene expression induced by lysophosphatidic acid:
      ephrinB1 gene up-regulation underlying neuropathic hyperalgesia and allodynia.
AB  - Lysophosphatidic acid (LPA) signaling, through LPA(1) receptor and its downstream
      RhoA, has been reported to initiate nerve injury-induced neuropathic pain. In the
      present study, we performed gene expression profiling of the dorsal root ganglion
      (DRG) to identify genes induced by intrathecal injection of LPA in a botulinum
      toxin C3 (BoNT/C3)-reversible manner. We selected and functionally characterized
      ephrinB1 from 82 identified genes as a potential gene involved in pain
      transmission, since ephrinB1 is implicated to modulate N-methyl-d-aspartate
      (NMDA) receptor functions in spinal pain transmission. The LPA-induced and
      BoNT/C3-reversible ephrinB1 gene expression was confirmed by quantitative real
      time PCR. Furthermore, treatments with an antisense oligodeoxynucleotide for
      ephrinB1 largely abolished the LPA-induced thermal hyperalgesia and allodynia in
      response to mechanical or Abeta-fiber-mediated electrical stimuli on day 1 after
      the injection. In addition, intrathecal treatment with a soluble ligand, ephrinB1
      Fc, caused similar neuropathic pain-like behaviors in a manner that was
      reversible by the NMDA receptor antagonist MK-801. These results suggest that
      ephrinB1 plays a crucial role in LPA-induced neuropathic pain. In addition, the
      present study may provide a new strategy to identify unique neuropathic pain
      related genes.

PMID- 19111590
TI  - Recombinant Mycobacterium smegmatis mc(2)155 vaccine expressing outer membrane
      protein 26 kDa antigen affords therapeutic protection against Helicobacter pylori
      infection.
AB  - Orally administered recombinant Mycobacterium smegmatis (rM. smegmatis) vaccines
      represent an attractive option for mass vaccination programmes against various
      infectious diseases. Therefore, in the present study, we evaluated the capacity
      of the outer membrane protein 26kDa antigen (Omp26) of Helicobacter pylori (H.
      pylori) to induce therapeutic protection against H. pylori infection in mice.
      Omp26 was cloned and expressed in M. smegmatis mc(2)155 as a fusion with the
      Mycobacterium fortuitum beta-lactamase protein under the control of the up
      regulated M. fortuitum beta-lactamase promoter, pBlaF. The rM. smegmatis strain
      was shown to be relatively stable in vitro in terms of plasmid stability and
      bacterial persistence. We found that oral immunization of H. pylori-infected mice
      with rM. smegmatis-Omp26 induced protection, i.e., significant reduction in
      bacterial colonization in the stomach. The protection was strongly related to
      serum specific antibodies with a Th(1) and Th(2) profile as well as to local
      cytokines in the stomach and spleen. These findings suggest that Omp26 is a
      promising vaccine candidate antigen for use in a therapeutic vaccine against H.
      pylori. The rM. smegmatis expressing Omp26 antigen could constitute an effective,
      low-cost combined vaccine against H. pylori.

PMID- 19111591
TI  - Effective protection by high efficiency bicistronic DNA vaccine against
      infectious bursal disease virus expressing VP2 protein and chicken IL-2.
AB  - Infectious bursal disease (IBD) is an acute and contagious viral infection of
      young chickens caused by IBD virus (IBDV). IBDV belongs to genus Avibirnavirus of
      family Birnaviridae. It is a non-enveloped virus with icosahedral symmetry that
      contains two segments of double-stranded RNA. The virus affects the lymphoid
      tissues of chickens, mainly the B cells of bursa of Fabricius, leading to severe
      and prolonged immunosuppression. VP2, a major structural protein of IBDV,
      contains antigenic epitopes responsible for induction of neutralizing/protective
      antibody. In the present study, VP2 gene of IBDV was cloned in a bicistronic
      vector along with chicken interleukin-2 (chiIL-2) as an adjuvant. An in vivo
      challenge study of bicistronic DNA vaccine expressing IBDV-VP2 and chicken IL-2
      showed effective protection against a lethal IBD infection in chickens. In
      addition, mortality, gross picture of bursa and histopathological findings
      demonstrated the efficacy of the vaccine in reducing virulence of the disease.

PMID- 19111592
TI  - Functional correlates for 5-HT(1A) receptors in maternally deprived rats
      displaying anxiety and depression-like behaviors.
AB  - Maternal separation is known to induce long-term changes in neuroendocrine and
      emotional responsiveness to stress in a large variety of models. We examined an
      animal model of early deprivation in Sprague-Dawley rats consisting of separating
      litters from their mothers and littermates 3 h daily during postnatal days 2 to
      15. In adulthood, maternally deprived rats in comparison with non-deprived
      controls exhibited an increase in anxiety and depression-related behaviors in the
      open-field and forced swim tests. Because serotonin (5-HT) 5-HT(1A) receptors
      seem to play an important role in the pathophysiology of major depression and in
      the mechanism of action of antidepressants, we investigated if 5-HT(1A) receptor
      function is altered in deprived rats. Although the hypothermic response to the 5
      HT(1A) receptor agonist 8-OH-DPAT was increased in adult deprived rats compared
      to non-deprived control group, no differences between groups were found in the
      effect of the systemic 8-OH-DPAT administration on serotoninergic cell firing in
      dorsal raphe nucleus and in the 5-HT release at the ventral hippocampus levels.
      These results suggest that 5-HT(1A) receptors are not substantially affected in
      adult Sprague-Dawley rats that were subjected to a maternal deprivation 3 h daily
      during the neonatal period.

PMID- 19111593
TI  - Ecklonia cava ethanolic extracts inhibit lipopolysaccharide-induced
      cyclooxygenase-2 and inducible nitric oxide synthase expression in BV2 microglia
      via the MAP kinase and NF-kappaB pathways.
AB  - Ecklonia cava (EC) is a brown alga that has demonstrated radical scavenging,
      bactericidal, tyrosinase inhibitory, and protease inhibitory activities. However,
      the molecular mechanisms underlying its anti-inflammatory action remain unclear.
      In the current study, we attempted to determine whether pretreatment with EC
      induces a significant inhibition of anti-inflammatory activity in
      lipopolysaccharide (LPS)-stimulated murine BV2 microglia. Our results indicate
      that EC inhibits LPS-induced nitric oxide (NO) and prostaglandin E(2) (PGE(2))
      production in a concentration-dependent manner and inhibits inducible nitric
      oxide (iNOS) and cyclooxygenase (COX)-2 in BV2 microglia without significant
      cytotoxicity. EC treatment significantly reduced nuclear factor-kappaB (NF
      kappaB) translocation and DNA-binding in LPS-stimulated BV2 microglia. This
      effect was mediated through the inhibition of the degradation of the inhibitor
      kappaB and by inhibition of the mitogen-activated protein kinase (MAPK)
      phosphorylation, at least in part by inhibiting the generation of reactive oxygen
      species. Our data also indicate that EC extracts exert anti-inflammatory effects
      by suppressing proinflammatory cytokines. Collectively, these results suggest
      that EC suppresses the induction of cytokines by LPS, as well as iNOS and COX-2
      expression, by blocking NF-kappaB and MAPK activation. These findings provide
      mechanistic insights into the anti-inflammatory and neuroprotective actions of EC
      in BV2 microglia.

PMID- 19111594
TI  - DNA damage, signalling and repair after exposure of cells to the sulphur mustard
      analogue 2-chloroethyl ethyl sulphide.
AB  - Sulphur mustard (SM) is a blistering agent that is directly toxic to the skin and
      mucosal surfaces of the eye and respiratory system. Symptoms take several hours
      to develop and the mechanism of action is poorly understood although SM is able
      to alkylate nucleic acids and proteins. The ability of SM to form adducts with
      DNA has been documented, although there are limited data demonstrating how cells
      respond to this insult to repair the damage. This study used the sulphur mustard
      surrogate 2-chloroethyl ethyl sulphide (CEES) to identify DNA damage repair
      pathways and signalling events that are activated after exposure to the agent. A
      dose-dependent increase in DNA damage was observed in TK6 lymphoblastoid cells,
      which was associated with a loss of cell viability. Using both model human
      lymphoblastoid cell lines and pharmacological inhibitors, it was found that DNA
      damage induced by CEES was repaired by base excision repair (BER) and nucleotide
      excision repair (NER) pathways. Finally, CEES was found to induce the
      phosphorylation of p53 and Chk2 and these events were mediated by both the ATM
      ataxia telangiectasia mutated and ATR (ATM and Rad-3 related) protein kinases.

PMID- 19111595
TI  - The differential regulation of steroidogenic acute regulatory protein-mediated
      steroidogenesis by type I and type II PKA in MA-10 cells.
AB  - Following tropic hormone challenge, steroidogenic tissues utilize PKA to
      phosphorylate unique subsets of proteins necessary to facilitate steroidogenesis.
      This includes the PKA-dependent expression and activation of the steroidogenic
      acute regulatory protein (STAR), which mediates the rate-limiting step of
      steroidogenesis by inducing the transfer of cholesterol from the outer to the
      inner mitochondrial membrane. Since both type I and type II PKA are present in
      steroidogenic tissues, we have utilized cAMP analog pairs that preferentially
      activate each PKA subtype in order to examine their impact on STAR synthesis and
      activity. In MA-10 mouse Leydig tumor cells Star gene expression is more
      dependent upon type I PKA, while the post-transcriptional regulation of STAR
      appears subject to type II PKA. These experiments delineate the discrete effects
      that type I and type II PKA exert on STAR-mediated steroidogenesis, and suggest
      complimentary roles for each subtype in coordinating steroidogenesis.

PMID- 19111597
TI  - Regional changes in the cholinergic system in mice lacking monoamine oxidase A.
AB  - Elevated brain monoamine concentrations resulting from monoamine oxidase A
      genetic ablation (MAOA knock-out mice) lead to changes in other neurotransmitter
      systems. To investigate the consequences of MAOA deficiency on the cholinergic
      system, we measured ligand binding to the high-affinity choline transporter
      (CHT1) and to muscarinic and nicotinic receptors in brain sections of MAOA knock
      out (KO) and wild-type mice. A twofold increase in [(3)H]-hemicholinium-3 ([(3)H]
      HC-3) binding to CHT1 was observed in the caudate putamen, nucleus accumbens, and
      motor cortex in MAOA KO mice as compared with wild-type (WT) mice. There was no
      difference in [(3)H]-HC-3 labeling in the hippocampus (dentate gyrus) between the
      two genotypes. Binding of [(125)I]-epibatidine ([(125)I]-Epi), [(125)I]-alpha
      bungarotoxin ([(125)I]-BGT), [(3)H]-pirenzepine ([(3)H]-PZR), and [(3)H]-AFDX-384
      ([(3)H]-AFX), which respectively label high- and low-affinity nicotinic
      receptors, M1 and M2 muscarinic cholinergic receptors, was not modified in the
      caudate putamen, nucleus accumbens, and motor cortex. A small but significant
      decrease of 19% in M1 binding densities was observed in the hippocampus (CA1
      field) of KO mice. Next, we tested acetylcholinesterase activity and found that
      it was decreased by 25% in the striatum of KO mice as compared with WT mice. Our
      data suggest that genetic deficiency in MAOA enzyme is associated with changes in
      cholinergic activity, which may account for some of the behavioral alterations
      observed in mice and humans lacking MAOA.

PMID- 19111596
TI  - Circadian controls outweigh acute illumination effects on the activity of
      extracellular signal-regulated kinase (ERK) in the retina.
AB  - Extracellular signal-regulated kinase (ERK) participates in numerous cellular
      functions including circadian-related activities. In the retina, the activity of
      ERK is under circadian control. However, it is not clear whether acute
      illumination changes or the circadian clocks in the retina have a larger impact
      on ERK activity, and the cellular distribution of activated ERK (pERK) as a
      function of circadian time in cone photoreceptors is not known. Chick embryos
      were exposed to the light or dark for various lengths of time after 12:12h light
      dark (LD) cycles, or on the second day of constant darkness after LD entrainment.
      Retinas were excised after various exposure times and relative ERK activity was
      determined by western immunoblotting. We also performed immunohistochemical and
      immunocytochemical stainings on circadian entrained retina sections and
      dissociated retina cells. There is about a fourfold difference in ERK activity
      between retinas harvested at circadian time (CT) 4 and CT 16, and the internal
      circadian control of ERK activity in the retina overcomes external light
      exposure. Also, during the subjective night, pERK was more apparent in the outer
      segment of cones, while pERK distribution was more uniform throughout the
      photoreceptors during the subjective day. Our results imply that the activity of
      retinal ERK is influenced more by circadian oscillators than acute illumination
      changes. Hence, the circadian oscillators in retina photoreceptors play a major
      role in the regulation of photoreceptor physiology, which leads to the circadian
      control of light sensitivity in photoreceptors.

PMID- 19111598
TI  - Alternative splicing and promoter use in TFII-I genes.
AB  - TFII-I proteins are ubiquitously expressed transcriptional factors involved in
      both basal transcription and signal transduction activation or repression. TFII-I
      proteins are detected as early as at two-cell stage and exhibit distinct and
      dynamic expression patterns in developing embryos as well as mark regional
      variation in the adult mouse brain. Analysis of atypical small and rare
      chromosomal deletions at 7q11.23 points to TFII-I genes (GTF2I and GTF2IRD1) as
      the prime candidates responsible for craniofacial and cognitive abnormalities in
      the Williams-Beuren syndrome. TFII-I genes are often subjected to alternative
      splicing, which generates isoforms that show different activities and play
      distinct biological roles. The coding regions of TFII-I genes are composed of
      more than 30 exons and are well conserved among vertebrates. However, their 5'
      untranslated regions are not as well conserved and all poorly characterized. In
      the present work, we analyzed promoter regions of TFII-I genes and described
      their additional exons, as well as tested tissue specificity of both previously
      reported and novel alternatively spliced isoforms. Our comprehensive analysis
      leads to further elucidation of the functional heterogeneity of TFII-I proteins,
      provides hints on search for regulatory pathways governing their expression, and
      opens up possibilities for examining the effect of different haplotypes on their
      promoter functions.

PMID- 19111600
TI  - Measurement of the binaural temporal window using a lateralisation task.
AB  - Binaural temporal resolution was measured using the discrimination of brief
      interaural time delays (ITDs). In experiment 1, three listeners performed a 2I
      2AFC, ITD-discrimination procedure. ITD changes of 8 to 1024micros were applied
      to brief probe noises. These probes, with durations of 16 to 362ms, were placed
      symmetrically in time within a 500-ms burst of otherwise interaurally
      uncorrelated noise. Psychometric functions were measured to obtain thresholds and
      temporal windows fitted to those thresholds. The best-fitting window was a
      symmetric roex shape (equivalent rectangular duration=197ms), an order of
      magnitude longer than monaural temporal windows and differed substantially from
      windows reported by Bernstein et al. [Bernstein, L.R., Trahiotis, C., Akeroyd,
      M.A., Hartung, K., 2001. Sensitivity to brief changes of interaural time and
      interaural intensity. J. Acoust. Soc. Am. 109, 1604-1615]. Experiment 2,
      replicated their main experiment, comparing their ITD-detection task with a
      similar discrimination procedure. Thresholds in the detection conditions were
      significantly better than those in the discrimination condition, particularly for
      short probe durations, indicating the use of an additional cue at these durations
      for the detection task and thus undermining the assumptions made in their window
      fit.

PMID- 19111599
TI  - Measurements of stapes velocity in live human ears.
AB  - Sound-induced stapes velocity (Vs) was measured intraoperatively in 14 patients
      undergoing cochlear implantation. All 14 patients had no history of middle-ear
      pathology, and their ossicular chains appeared normal on intraoperative
      inspection and palpation. The magnitude of the mean Vs (normalized by
      simultaneously-measured ear-canal sound pressure) was stiffness-dominated at
      frequencies below 1 kHz, increased up to approximately 4 kHz, and then decreased
      at higher frequencies. The phase of the mean velocity was +0.2 periods at 0.3
      kHz, and gradually became a phase lag at higher frequencies. The mean Vs measured
      in this study was similar to that of seven ears reported in the only other
      published study of live human measurements (Huber et al., 2001). We also made
      measurements of Vs in fresh cadaveric temporal bones using a technique identical
      to that used in live ears, including similar measurement angles and location. The
      mean Vs measured in the cadaveric ears under these conditions was similar to the
      mean Vs measurements in the 14 live ears. This indicates that middle-ear
      mechanics are similar in live and cadaveric ears. In addition, interspecies
      comparisons were made between our live human Vs and the Vs reported in different
      animal studies. There were some clear similarities in Vs across species, as well
      as differences. The primary interspecies differences were in the magnitude of the
      Vs as well as in the frequency of transitions in the magnitudes' frequency
      dependence from rising to flat or falling.

PMID- 19111601
TI  - Aging outer hair cells (OHCs) in the Fischer 344 rat cochlea: function and
      morphology.
AB  - As previously reported [Popelar, J., Groh, D., Pelanova, J., Canlon, B., Syka,
      J., 2006. Age-related changes in cochlear and brainstem auditory functions in
      Fischer 344 rats. Neurobiol. Aging 27, 490-500; Buckiova, D., Popelar, J., Syka,
      J., 2007. Aging cochleas in the F344 rat: morphological and functional changes.
      Exp. Gerontol. 42, 629-638; Bielefeld, E.C., Coling, D., Chen, G.D., Li, M.N.,
      Tanaka, C., Hu, B.H., Henderson, D., 2008. Age-related hearing loss in the
      Fischer 344/NHsd rat substrain. Hear. Res. 241, 26-33], aged Fischer 344 (F344)
      rats with severe hearing loss retain many outer hair cells (OHCs) especially in
      the middle turn of the cochlea. The current study confirmed the previous findings
      showing that aged OHCs were present, but dysfunctional. Distortion product
      otoacoustic emissions (DPOAE), which are believed to reflect in vivo OHC
      motility, were absent in the aged rats while the majority of OHCs (>80%) were
      present and morphologically intact. There was no detectable injury of OHC
      stereocilia as assessed by actin-staining and examination under the light
      microscope. Cochlear microphonics (CM) at 12kHz, recorded from the middle turn,
      only showed a slight age-related reduction, indicating a normal mechanoelectrical
      transduction apparatus in the remaining OHCs in the cochlear regions with 10-20%
      OHC loss. Activities of succinate dehydrogenase (SDH), an enzyme shared by the
      citric acid cycle and the mitochondrial electron transport chain (METC), were
      also at normal levels in aged OHCs. Importantly, aged OHCs showed reduced levels
      of prestin immunolabeling compared to young controls. Together with our previous
      finding showing that the stria vascularis and endocochlear potential were
      essentially normal in aged F344 rats [Bielefeld, E.C., Coling, D., Chen, G.D.,
      Li, M.N., Tanaka, C., Hu, B.H., Henderson, D., 2008. Age-related hearing loss in
      the Fischer 344/NHsd rat substrain. Hear. Res. 241, 26-33], the results suggest
      that disruption of prestin is the major cause of DPOAE loss and loss of cochlear
      sensitivity.

PMID- 19111602
TI  - Memory improvement in ibotenic acid induced model rats by extracts of Scutellaria
      baicalensis.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: Scutellaria baicalensis Georgi (Labiatae)
      extracts have been used as traditional Korean medicine, to treat cerebral
      ischemia in addition to bacterial infection and inflammatory diseases. AIM OF THE
      STUDY: The improvement effect on learning and memory by the administration of
      Scutellaria baicalensis extracts was evaluated and the underlying mechanisms were
      investigated. MATERIALS AND METHODS: Memory behavior was tested by the passive
      avoidance test and Y-maze test. We also investigated the cells expressing
      neuronal markers related to memory processes by immunofluorescence staining
      analysis in memory deficient animal model (Ibo model) rats and in hippocampal
      progenitor cells. RESULTS: We found neuronal cells immunoreactive to choline
      acetyltransferase (ChAT), a marker for cholinergic neurons were increased in the
      hippocampus, while cells producing GABA and glutamate were not after 30 mg/kg
      Scutellaria baicalensis administration. Futhermore, Scutellaria baicalensis
      extracts enhanced the survival of a hippocampal progenitor cell line, HiB5 and
      its differentiation to ChAT immunoreactive cells. The increased expression of
      memory related neurotransmitter, NMDA receptor and a reduction of activated
      microglia in the hippocampus were also observed in the Ibo model when
      administrated Scutellaria baicalensis extracts. CONCLUSIONS: These results imply
      that Scutellaria baicalensis has significant neuroprotective effects in the Ibo
      model.

PMID- 19111604
TI  - Extracellular guanosine and GTP promote expression of differentiation markers and
      induce S-phase cell-cycle arrest in human SH-SY5Y neuroblastoma cells.
AB  - SH-SY5Y neuroblastoma cells, a model for studying neuronal differentiation, are
      able to differentiate into either cholinergic or dopaminergic/adrenergic
      phenotypes depending on media conditions. Using this system, we asked whether
      guanosine (Guo) or guanosine-5'-triphosphate (GTP) are able to drive
      differentiation towards one particular phenotype. Differentiation was determined
      by evaluating the frequency of cells bearing neurites and assessing neurite
      length after exposure to different concentrations of Guo or GTP for different
      durations. After 6 days, 0.3 mM Guo or GTP induced a significant increase in the
      number of cells bearing neurites and increased neurite length. Western blot
      analyses confirmed that purines induced differentiation; cells exposed to purines
      showed increases in the levels of GAP43, MAP2, and tyrosine hydroxylase.
      Proliferation assays and cytofluorimetric analyses indicated a significant anti
      proliferative effect of purines, and a concentration-dependent accumulation of
      cells in S-phase, starting after 24 h of purine exposure and extending for up to
      6 days. A transcriptional profile analysis using gene arrays showed that an up
      regulation of cyclin E2/cdk2 evident after 24 h was responsible for S-phase
      entry, and a concurrent down-regulation of cell-cycle progression-promoting
      cyclin B1/B2 prevented S-phase exit. In addition, patch-clamp recordings revealed
      that 0.3 mM Guo or GTP, after 6 day incubation, significantly decreased Na(+)
      currents. In conclusion, we showed Guo- and GTP-induced cell-cycle arrest in
      neuroblastoma cells and suggest that this makes these cells more responsive to
      differentiation processes that favor the dopaminergic/adrenergic phenotype.

PMID- 19111603
TI  - Echinacea increases arginase activity and has anti-inflammatory properties in RAW
      264.7 macrophage cells, indicative of alternative macrophage activation.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: The genus Echinacea is a popular herbal
      immunomodulator. Recent reports indicate that Echinacea products inhibit nitric
      oxide (NO) production in activated macrophages. AIM OF THE STUDY: In the present
      study we determined the inhibitory effects of alcohol extracts and individual
      fractions of alcohol extracts of Echinacea on NO production, and explored the
      mechanism underlying the pharmacological anti-inflammatory activity. MATERIALS
      AND METHODS: Alcohol extracts of three medicinal Echinacea species, Echinacea
      angustifolia, Echinacea pallida and Echinacea purpurea, were prepared using
      Soxhlet apparatus and fractionated using HPLC. NO production by LPS activated RAW
      264.7 macrophage cells was measured using a Griess reagent and iNOS detected
      using immunoblotting. In addition, effects on arginase activity were measured in
      RAW 264.7 cells stimulated with 8-bromo-cAMP +/- LPS. RESULTS: Alcohol extracts
      of all three Echinacea species significantly inhibited NO production by
      lipopolysaccharide (LPS)-activated the RAW 264.7 macrophage cell line; among them
      Echinacea pallida was the most active. The Echinacea-mediated decrease in NO
      production was unlikely due to a direct scavenging of NO because the extracts did
      not directly inhibit NO released from an NO donor, sodium nitroprusside. An
      immunoblotting assay demonstrated that the extract of Echinacea pallida inhibited
      inducible nitric oxide synthase (iNOS) protein expression in LPS-treated
      macrophages. The enzymes iNOS and arginase metabolize a common substrate, l
      arginine, but produce distinct biological effects. While iNOS is involved in
      inflammatory response and host defense, arginase participates actively in anti
      inflammatory activation. Arginase activity of RAW 264.7 cells stimulated with 8
      bromo-cAMP was significantly increased by alcohol extracts of all three Echinacea
      species. The polar fraction containing caffeic acid derivatives enhanced arginase
      activity, while the lipophilic fraction containing alkamides exhibited a
      potential of inhibiting NO production and iNOS expression. CONCLUSIONS: These
      results suggest that the anti-inflammatory activity of Echinacea might be due to
      multiple active metabolites, which work together to switch macrophage activation
      from classical activation towards alternative activation.

PMID- 19111605
TI  - Response to "The microEST in vitro test for embryotoxicity - a case of mistaken
      identity?" by Robert Combes.

PMID- 19111606
TI  - Polymerase chain reaction-single strand conformation polymorphism applied to sex
      identification of Accipiter cooperii.
AB  - Determination of sex in birds is valuable for studying population dynamics and
      structure, habitat use, behavior and mating systems. The purpose of the present
      study was to optimize a DNA-based methodology to allow the sex identification in
      Accipiter cooperii nestlings. Chromo-helicase-DNA-binding (CHD1) gene was used in
      this work as a marker for sex identification. CHD-W and CHD-Z sequences should
      present length and/or sequence differences providing a way to identify gender. We
      used a non-invasive method for DNA extraction from feathers and performed
      polymerase chain reaction-single strand conformation polymorphism (PCR-SSCP)
      method. The length difference between CHD-W and CHD-Z amplified fragments
      observed by electrophoresis in conventional agarose gel was not enough to provide
      a clear differentiation between males and females. However, patterns obtained by
      PCR-SSCP differentiated undoubtedly males and females in A. cooperii. This tool
      provides a precise gender identification assay and will be applied to confirm and
      refine morphometrically based sexing techniques used in the field.

PMID- 19111607
TI  - Reactive oxygen species are involved in FasL-induced caspase-independent cell
      death and inflammatory responses.
AB  - Fas-mediated caspase-dependent cell apoptosis has been well investigated.
      However, recent studies have shown that Fas can induce nonapoptotic caspase
      independent cell death (CICD) when caspase activity is inhibited. Currently, the
      molecular mechanism of this alternative cell death mediated by Fas remains
      unclear. In this study, we investigated the signaling pathway of Fas-induced CICD
      in mouse embryonic fibroblasts (MEFs) whose caspase function was disrupted by the
      pan-caspase inhibitor Z-VAD-FMK and its coupling to inflammatory responses. Our
      results revealed that receptor-interacting protein 1 and tumor necrosis factor
      receptor-associated factor 2 play important roles in FasL-induced CICD. This
      death is associated with intracellular reactive oxygen species (ROS) production
      from mitochondria, as a ROS scavenger (BHA), antioxidants (trolox, NAC), and a
      mitochondrial respiratory chain uncoupler (rotenone) could prevent this event.
      Furthermore, delayed and sustained JNK activation, mitochondrial membrane
      potential breakdown, and loss of intracellular GSH were observed. In addition to
      CICD, FasL also induces cyclooxygenase-2 and MIP-2 gene upregulation, and both
      responses are attributed to ROS-dependent JNK activation. Taken together, these
      results demonstrate alternative signaling pathways of Fas upon caspase inhibition
      in MEFs that are unrelated to the classical apoptotic pathway, but steer cells
      toward necrosis and an inflammatory response through ROS production.

PMID- 19111608
TI  - The wanderings of a free radical.
AB  - In my career I have moved from chemistry to biochemistry to plant science to
      clinical chemistry and back again (in a partial way) to plants. This review
      presents a brief history of my research achievements (ascorbate-glutathione
      cycle, role of iron in oxidative damage and human disease, biomarkers of free
      radical damage, and studies on atherosclerosis and neurodegeneration) and how
      they relate to my research activities today. The field of free radicals/other
      reactive species/antioxidants underpins all of modern Biology. These agents
      helped to drive human evolution and the basic principles of the field are
      repeatedly found to be relevant in other research areas. It was an exciting field
      when I started some 40 years ago, and it still is today, but some major
      challenges must be faced.

PMID- 19111609
TI  - A unique thioredoxin of the parasitic nematode Haemonchus contortus with
      glutaredoxin activity.
AB  - The dependency of parasites on the cellular redox systems has led to their
      investigation as novel drug targets. Defence against oxidative damage is through
      the thioredoxin and glutathione systems. The classic thioredoxin is identified by
      the active site Cys-Gly-Pro-Cys (CGPC). Here we describe the identification of a
      unique thioredoxin in the parasitic nematode, Haemonchus contortus. This
      thioredoxin-related protein, termed HcTrx5, has an arginine in its active site
      (Cys-Arg-Ser-Cys; CRSC) that is not found in any other organism. Recombinant
      HcTrx5 was able to reduce the disulfide bond in insulin, and be regenerated by
      mammalian thioredoxin reductase with a K(m) 2.19+/-1.5 microM, similar to the
      classic thioredoxins. However, it was also able to reduce insulin when
      glutathione and glutathione reductase replaced the thioredoxin reductase. When
      coupled with H. contortus peroxiredoxin, HcTrx5 was active using either the
      thioredoxin reductase or the glutathione and glutathione reductase. HcTrx5 is
      expressed through the life cycle, with highest expression in the adult stage. The
      unique activity of this thioredoxin makes it a potential drug target for the
      control of this parasite.

PMID- 19111610
TI  - Modulation of inflammation by vitamin E and C supplementation prior to anterior
      cruciate ligament surgery.
AB  - Muscle atrophy commonly follows anterior cruciate ligament (ACL) injury and
      surgery. Proinflammatory cytokines can induce and exacerbate oxidative stress,
      potentiating muscle atrophy. The purpose of this study was to evaluate the
      influence of prior antioxidant (AO) supplementation on circulating cytokines
      following ACL surgery. A randomized, double-blind, placebo-controlled trial was
      conducted in men undergoing ACL surgery, who were randomly assigned to either:
      (1) AO (200 IU of vitamin E (50% d-alpha-tocopheryl acetate and 50% d-alpha
      tocopherol) and 500 mg ascorbic acid), or (2) matching placebos (PL). Subjects
      took supplements twice daily for 2 weeks prior to and up to 12 weeks after
      surgery. Each subject provided five blood samples: (1) baseline (Bsl, prior to
      supplementation and approximately 2 weeks prior to surgery), (2) presurgery
      (Pre), (3) 90 min, (4) 72 h, and (5) 7 days postsurgery. Following surgery,
      inflammation and muscle damage increased in both groups, as assessed by increased
      circulating IL-6, C-reactive protein, and creatine kinase. During AO
      supplementation, plasma alpha-T and AA increased while gamma-T concentrations
      decreased significantly (P< 0.05). At 90 min the AO group displayed a significant
      decrease in AA, an inverse correlation between AA and (interleukin) IL-8 (r(2)=
      0.50, P< 0.05), and a significantly lower IL-10 response than that of the PL
      group. IL-10 was significantly elevated at 90 min and 72 h in the PL group. In
      summary, our findings show that circulating inflammatory cytokines increase and
      AO supplementation attenuated the increase in IL-10 in patients post-ACL surgery.

PMID- 19111612
TI  - Effect of soil sample preservation, compared to the effect of other environmental
      variables, on bacterial and eukaryotic diversity.
AB  - Archived soil samples are a valuable source for retrospective ecological studies,
      and their recent analysis using molecular ecological approaches has drawn
      significant attention within the scientific community. However, the possibility
      of addressing ecological questions regarding detectable microbiota in dried and
      extensively stored soils has not yet been fully evaluated. To achieve this, soil
      samples collected from two long-term grassland experiments in the United Kingdom
      and The Netherlands were subjected to air-drying at 40-42 degrees C and stored at
      room temperature. Total bacterial, Bacillus benzoevorans-related and eukaryotic
      communities associated with these samples were analyzed by DGGE-fingerprinting of
      PCR-amplified ribosomal RNA gene fragments. Changes in microbial community
      structure due to drying and storage were evaluated by multivariate analysis in
      relation to changes caused by other environmental conditions, such as soil pH,
      type of fertilizer and vegetation. Soil drying and storage affected the
      detectable community structure, but did not materially impair our capacity to
      identify the effect of soil parameters studied in long-term grassland
      experiments. Although, in some cases, the amplitude of the influence of a given
      parameter changed due to sample preservation, analyses revealed that pH,
      fertilization and soil type significantly influenced microbial community
      structure in the analyzed samples.

PMID- 19111613
TI  - The role of redox status on chemokine expression in acute pancreatitis.
AB  - This study focused on the involvement of oxidative stress in the mechanisms
      mediating chemokine production in different cell sources during mild and severe
      acute pancreatitis (AP) induced by bile-pancreatic duct obstruction (BPDO) and
      3.5% NaTc, respectively. N-Acetylcysteine (NAC) was used as antioxidant
      treatment. Pancreatic glutathione depletion, acinar overexpression of monocyte
      chemoattractant protein-1 (MCP-1) and cytokine-induced neutrophil chemoattractant
      (CINC), and activation of p38MAPK, NF-kappaB and STAT3 were found in both AP
      models. NAC reduced the depletion of glutathione in BPDO- but not in NaTc-induced
      AP, in which oxidative stress overwhelmed the antioxidant capability of NAC. As a
      result, inhibition of the acinar chemokine expression and signalling pathways
      occurs in mild, but not in severe AP. However, MCP-1 and CINC expressions in
      whole pancreas and plasma chemokine levels were not reduced by NAC, even in BPDO
      induced AP, suggesting that in addition to acini, other pancreatic cells produced
      chemokines by antioxidant resistant mechanisms. The high Il-6 plasma levels found
      during AP, both in NAC-treated and non-treated rats, pointed out cytokines as
      activating factors of chemokine expression in non-acinar cells. In conclusion,
      from early AP oxidant-mediated MAPK, NF-kappaB and STAT3 activation triggers the
      chemokine expression in acini but not in non-acinar cells.

PMID- 19111611
TI  - Physical properties of lipid bilayers from EPR spin labeling and their influence
      on chemical reactions in a membrane environment.
AB  - The influence of a variety of microenvironmental factors on the inherent
      reactivity of membrane-located reagents is poorly understood. A goal of this
      review is to provide detailed profiles of membrane properties, including
      hydrophobicity, oxygen and nitric oxide solubility and diffusion rates, bilayer
      penetration of metal ions and metal-ion complexes, and membrane order and
      fluidity, that can be obtained with EPR spin-labeling methods. These properties
      can drastically vary with membrane composition, membrane depth, and membrane
      domain formation, influencing the fate of chemical reactions that occur in a
      lipid bilayer environment.

PMID- 19111614
TI  - Nanoscale mechanical measurement determination of the glass transition
      temperature of poly(lactic acid)/everolimus coated stents in air and dissolution
      media.
AB  - Localized atomic force microscopy (AFM) force analysis on poly(lactic acid) (PLA)
      and poly(lactic acid)/everolimus coated stents has been performed under ambient
      conditions. Similar Young's modulus were derived from both PLA and PLA/everolimus
      stent surface, namely 2.25+/-0.46 and 2.04+/-0.39GPa, respectively, indicating
      that the drug, everolimus does not significantly effect the mechanical properties
      of PLA up to a 1:1 (w/w) drug loading. Temperature controlled force measurements
      on PLA only coated stents in air and in a 1% Triton surfactant solution allowed
      the glass transition temperature (T(g)) of the polymer to be determined. A
      significant drop of the Young's modulus in solution was observed at 36 degrees C,
      suggests that in vivo the T(g) of the polymer is below body temperature. The
      possible consequences on drug release and the mechanisms by which this may occur
      are considered.

PMID- 19111615
TI  - Proton-pyrophosphatase and polyphosphate in acidocalcisome-like vesicles from
      oocytes and eggs of Periplaneta americana.
AB  - Acidocalcisomes are acidic organelles containing large amounts of polyphosphate
      (poly P), a number of cations, and a variety of cation pumps in their limiting
      membrane. The vacuolar proton-pyrophosphatase (V-H(+)-PPase), a unique
      electrogenic proton-pump that couples pyrophosphate (PPi) hydrolysis to the
      active transport of protons across membranes, is commonly present in membranes of
      acidocalcisomes. In the course of insect oogenesis, a large amount of yolk
      protein is incorporated by the oocytes and stored in organelles called yolk
      granules (YGs). During embryogenesis, the content of these granules is degraded
      by acid hydrolases. These enzymes are activated by the acidification of the YG by
      a mechanism that is mediated by proton-pumps present in their membranes. In this
      work, we describe an H(+)-PPase activity in membrane fractions of oocytes and
      eggs of the domestic cockroach Periplaneta americana. The enzyme activity was
      optimum at pH around 7.0, and was dependent on Mg(2+) and inhibited by NaF, as
      well as by IDP and Ca(2+). Immunolocalization of the yolk preparation using
      antibodies against a conserved sequence of V-H(+)-PPases showed labeling of small
      vesicles, which also showed the presence of high concentrations of phosphorus,
      calcium and other elements, as revealed by electron probe X-ray microanalysis. In
      addition, poly P content was detected in ovaries and eggs and localized inside
      the yolk granules and the small vesicles. Altogether, our results provide
      evidence that numerous small vesicles of the eggs of P. americana present
      acidocalcisome-like characteristics. In addition, the possible role of these
      organelles during embryogenesis of this insect is discussed.

PMID- 19111616
TI  - The alpha-chemokine CXCL14 is up-regulated in the sciatic nerve of a mouse model
      of Charcot-Marie-Tooth disease type 1A and alters myelin gene expression in
      cultured Schwann cells.
AB  - At present the pathogenesis of CMT1A neuropathy, caused by the overexpression of
      PMP22, has not yet been entirely understood. The PMP22-overexpressing C61 mutant
      mouse is a suitable animal model, which mimics the human CMT1A disorder. We
      observed that myelin gene expression in the sciatic nerve of the C61 mouse was up
      regulated at postnatal day 4 to 7 (P4-P7). When investigating the morphology of
      peripheral nerves in C61 and wildtype mice at early stages of postnatal
      development, hypermyelination could be detected in the femoral quadriceps and
      sciatic nerve of transgenic animals at postnatal day 7 (P7). In order to identify
      genes, other than Pmp22, that are modulated in sciatic nerve of P7 transgenic
      mice, we applied microarray technology. Amongst the regulated genes, the gene
      encoding the alpha-chemokine CXCL14 was most prominently up-regulated. We report
      that Cxcl14 was expressed exclusively by Schwann cells of the sciatic nerve, as
      well as by cultured Schwann cells triggered to differentiate. Furthermore, in
      cultured Schwann cells CXCL14 modulated the expression of myelin genes and
      altered cell proliferation. Our findings demonstrate that early overexpression of
      PMP22, in a mouse model of CMT1A, results in a strong up-regulation of CXCL14,
      which seems to play a novel regulatory role in Schwann cell differentiation.

PMID- 19111617
TI  - Formation of posterior cranial placode derivatives requires the Iroquois
      transcription factor irx4a.
AB  - Members of the Iroquois (Irx) homeodomain transcription factor gene family have
      been implicated in a variety of early developmental processes, including neural
      pre-patterning, tissue differentiation, neural crest development and cranial
      placode formation. Here, we report that, in zebrafish, the irx4a gene
      participates in specification of a number of placode derivatives that arise from
      the posterior placodal field. Specifically, differentiation of the trigeminal,
      epibranchial and lateral line placodes are affected when irx4a function is
      interrupted using antisense morpholino oligonucleotides. We show that both in the
      trigeminal ganglion and in the lateral line, irx4a is involved in controlling the
      number of sensory cells that develop. Other phenotypes observed in morphant
      embryos include misspecification of the heart chambers and failure of retinal
      ganglion and photoreceptor cell differentiation, functions described previously
      for Irx4 in other species. We also provide evidence that irx4a regulates the
      expression of the sox2 gene, both in the neural plate and in progenitor cells of
      the lateral line system. Our results point to irx4a as a critical gene for
      numerous developmental processes and highlight its role in the formation of
      placodal derivatives in vertebrates.

PMID- 19111619
TI  - Solubility survey of fragments of the neurofibromatosis type 1 protein
      neurofibromin.
AB  - The protein giant neurofibromin (320kDa) is the protein product of the NF1 tumor
      suppressor gene, alterations of which are responsible for the pathogenesis of
      neurofibromatosis type 1 (NF1). Neurofibromin is a Ras-specific GTPase activating
      protein (RasGAP) that, 15 years after the cloning of the gene, remains the only
      clearly defined function of the protein. In a structural proteomics approach, we
      aimed at defining functions beyond RasGAP activity based on the discovery of
      structural modules. Given the poor outcome of domain prediction tools, we have
      undertaken a fragment solubility survey covering the full protein sequence, with
      the aim of defining new domain boundaries or fragments that could be investigated
      by biochemical methods including structural analysis. More than 200 constructs
      have been expressed and tested for solubility in small scale assays. Boundaries
      were chosen based upon secondary structure predictions, sequence conservation
      among neurofibromin orthologues and chemical properties of amino acids. Using
      this strategy we recently discovered a novel bipartite module in neurofibromin.
      We have expanded our study to include ESPRIT, a library-based construct screen,
      to perform fragment testing at a finer level with respect to the choice of
      terminal residues. Our study confirms earlier notions about the challenges
      neurofibromin presents to the biochemist and points to strategies whereby the
      success rate may be enhanced in the future.

PMID- 19111620
TI  - Enhancement of immunity and disease resistance in the white shrimp, Litopenaeus
      vannamei, by the probiotic, Bacillus subtilis E20.
AB  - Effects of Bacillus subtilis E20 isolated from fermented soybean on immune
      parameters and the disease resistance of the white shrimp (Litopenaeus vannamei)
      after 98 days of B. subtilis E20 feeding were evaluated in this study. Shrimp fed
      B. subtilis E20-containing diets at concentrations of 10(6) (E206), 10(7) (E207),
      and 10(8) (E208)cfu kg(-1), respectively, had significantly increased survival
      rates of 13.3%, 16.7%, and 20%, compared to the control (fed no probiotic) after
      being challenged with Vibrio alginolyticus. There were no significant differences
      in the total hemocyte count, respiratory burst, or superoxide dismutase
      glutathione peroxidase among all treatments. Shrimp fed a higher concentration of
      the probiotic (E208) exhibited significant increases in phenoloxidase activity,
      phagocytic activity, and clearance efficiency compared to control shrimp. In
      addition, B. subtilis E20 showed a weaker inhibitory effect against the growth of
      Aeromona hydrophila with around a 0.3-cm inhibitory zone, but showed no
      inhibitory effects against other selected pathogens, such as white shrimp
      pathogens: V. alginolyticus and Vibrio vulnificus. These results suggest that the
      increased resistance of shrimp after B. subtilis E20 consumption occurs through
      immune modifications, such as increases in phenoloxidase activity, phagocytic
      activity, and clearance efficiency against V. alginolyticus.

PMID- 19111618
TI  - In vivo assembly and single-molecule characterization of the transcription
      machinery from Shewanella oneidensis MR-1.
AB  - Harnessing the new bioremediation and biotechnology applications offered by the
      dissimilatory metal-reducing bacteria, Shewanella oneidensis MR-1, requires a
      clear understanding of its transcription machinery, a pivotal component in
      maintaining vitality and in responding to various conditions, including
      starvation and environmental stress. Here, we have reconstituted the S.
      oneidensis RNA polymerase (RNAP) core in vivo by generating a co-overexpression
      construct that produces a long polycistronic mRNA encoding all of the core
      subunits (alpha, beta, beta', and omega) and verified that this reconstituted
      core is capable of forming fully functional holoenzymes with the S. oneidensis
      sigma factors sigma(70), sigma(38), sigma(32), and sigma(24). Further, to
      demonstrate the applications for this reconstituted core, we report the
      application of single-molecule fluorescence resonance energy transfer (smFRET)
      assays to monitor the mechanisms of transcription by the S. oneidensis sigma(70)
      RNAP holoenyzme. These results show that the reconstituted transcription
      machinery from S. oneidensis, like its Escherichia coli counterpart, "scrunches"
      the DNA into its active center during initial transcription, and that as the
      holoenzyme transitions into elongation, the release of sigma(70) is non
      obligatory.

PMID- 19111621
TI  - Use of fractional anisotropy for determination of the cut-off value in 11C
      methionine positron emission tomography for glioma.
AB  - Multimodal imaging is one of the necessary steps in the treatment of malignant
      brain tumors, and use of magnetic resonance imaging (MRI) and positron emission
      tomography (PET) are the current gold standard technique for the morphological
      and biological assessment of malignant brain tumors. In addition, fractional
      anisotropy (FA) obtained from diffusion tensor imaging (DTI) and 11C-methionine
      PET are useful to determine the tumor border at the tumor and white matter
      interface. Although there is no question of their value, a universally accepted
      cut-off value to discriminate normal and abnormal tissue has not been
      established. In this study we attempted to calculate and determine the cut-off
      values in FA and 11C-methionine PET that will allow delineation of the tumor
      border at the tumor and white matter interface by combining these two modalities.
      We were able to determine individual cut-off values for 11 patients, and then
      found an average cut-off value in the T/N ratio of 11C-methionine PET of 1.27 and
      in FA of 0.26, values similar to those previously confirmed by histological
      study. Moreover, reconstructing images delineating the tumor border was possible
      combining these two imaging modalities. We propose that the combined analysis of
      DTI and 11C-methionine PET has the potential to improve tumor border imaging in
      glioma patients, providing important information for establishing neurosurgical
      strategies.

PMID- 19111623
TI  - Judgment of actions in experts: a high-resolution EEG study in elite athletes.
AB  - The present study tested the two following hypotheses: (i) compared to non
      athletes, elite athletes are characterized by a reduced cortical activation
      during the judgment of sporting observed actions; (ii) in elite athletes, a good
      judgment of observed sporting actions is related to a low cortical activation. To
      address these issues, electroencephalographic (EEG) data were recorded in 15
      elite rhythmic gymnasts and 13 non-gymnasts. They observed a series of 120
      rhythmic gymnastic videos. At the end of each video, the subjects had to judge
      the artistic/athletic level of the exercise by a scale from 0 to 10. The mismatch
      between their judgment and that of the coach indexed the degree of action
      judgment. The EEG cortical sources were estimated by sLORETA. With reference to a
      pre-stimulus period, the power decrease of alpha (8-12 Hz) rhythms during the
      videos indexed the cortical activation (event related desynchronization, ERD).
      Regarding the hypothesis (i), low- and high-frequency alpha ERD was lower in
      amplitude in the elite rhythmic gymnasts compared to the non-gymnasts in
      occipital and temporal areas (ventral pathway) and in dorsal pathway. Regarding
      the hypothesis (ii), in the elite rhythmic gymnasts high-frequency alpha ERD was
      higher in amplitude with the videos characterized by a high judgment error than
      those characterized by a low judgment error; this was true in inferior posterior
      parietal and ventral premotor areas ("mirror" pathway). These results globally
      suggest that the judgment of observed sporting actions is related to low
      amplitude of alpha ERD, as a possible index of spatially selective cortical
      activation ("neural efficiency").

PMID- 19111622
TI  - Inter-subject variability in hypercapnic normalization of the BOLD fMRI response.
AB  - In the application of hypercapnic normalization to functional magnetic resonance
      imaging (fMRI) studies, the blood oxygenation level dependent (BOLD) response to
      a functional stimulus is typically divided by the BOLD response to a hypercapnic
      challenge. While some prior studies have shown that hypercapnic normalization can
      reduce inter-subject BOLD variability, other studies have found an increase in
      inter-subject variability. In this study we used measures of baseline cerebral
      blood flow (CBF) and the functional BOLD and CBF responses to both visual stimuli
      and hypercapnia to assess the effect of hypercapnic normalization on inter
      subject variability. We found that the functional and hypercapnic BOLD and CBF
      responses all exhibited a significant inverse dependence on baseline CBF. In
      contrast, the maximum BOLD response was independent of baseline CBF and was not a
      major source of inter-subject BOLD variability. Division of the functional BOLD
      response by the hypercapnic BOLD response increased inter-subject variability in
      the normalized responses as compared to the original responses, reflecting the
      presence of a systematic bias term that was inversely dependent on the
      hypercapnic BOLD response. This systematic bias resulted from a positive
      intercept term in the linear relationship between the functional and hypercapnic
      BOLD responses. This positive intercept term reflected a steeper inverse
      dependence of the hypercapnic CBF response on baseline CBF, as compared to the
      functional CBF response. In contrast to the results obtained with normalization
      based on division, normalized responses obtained by using the hypercapnic BOLD
      response as a covariate were unaffected by the systematic bias and exhibited
      reduced inter-subject variability. The findings of this study indicate that the
      positive intercept in the linear relationship between functional and hypercapnic
      BOLD responses should be carefully considered in the hypercapnic normalization of
      BOLD fMRI data.

PMID- 19111624
TI  - Decoding sequential stages of task preparation in the human brain.
AB  - The flow of information from sensory stimuli to motor responses in the human
      brain can be flexibly re-routed depending on task demands. However, it has
      remained unclear which sequence of processes is involved in preparing the brain
      for an upcoming task. Here, we used a combination of fMRI and multivariate
      pattern classification to decompose the information flow in a task-switching
      experiment. Specifically, we present a time-resolved decoding approach that
      allowed us to track the temporal buildup of task-related information. This
      approach also allowed us to distinguish encoding of the task from encoding of
      target stimuli and motor responses, thus separating between different components
      of information processing. We were able to decode from parietal and lateral
      prefrontal cortex which specific task-set a subject was currently holding.
      Importantly, this revealed that the intraparietal sulcus encoded task-set
      information before prefrontal cortex, and it was the only region to encode the
      specific task-set before the relevant target stimulus was presented. This
      suggests that task-related information in parietal cortex does not rely on input
      from prefrontal cortex as previously suggested. In contrast, our findings suggest
      that parietal cortex might play a role in establishing task-sets in prefrontal
      cortex.

PMID- 19111625
TI  - Towards brain repair: Insights from teleost fish.
AB  - In the adult mammalian brain, the ability to minimize secondary cell death after
      injury, and to repair nervous tissue through generation of new neurons, is
      severely compromised. By contrast, certain taxa of non-mammalian vertebrates
      possess an enormous potential for regeneration. Examination of one of these taxa,
      teleost fish, has revealed a close link between this phenomenon and constitutive
      adult neurogenesis. Key factors mediating successful regeneration appear to be:
      elimination of damaged cells by apoptosis, instead of necrosis; activation of
      mechanisms that prevent the occurrence of secondary cell death; increased
      production of new neurons that replace neurons lost to injury; and activation of
      developmental mechanisms that mediate directed migration of the new cells to the
      site of injury, the differentiation of the young cells, and their integration
      into the existing neural network. Comparative analysis has suggested that
      constitutive adult neurogenesis is a primitive vertebrate trait, the main
      function of which has been to ensure a numerical matching between muscle
      fibers/sensory receptor cells and central elements involved in motor
      control/processing of sensory information associated with these peripheral
      elements. It is hypothesized that, when in the course of the evolution of mammals
      a major shift in the growth pattern from hyperplasia to hypertrophy took place,
      the number of neurogenic brain regions and new neurons markedly decreased. As a
      consequence, the potential for neuronal regeneration was greatly reduced, but
      remnants of neurogenic areas have persisted in the adult mammalian brain in form
      of quiescent stem cells. It is likely that the study of regeneration-competent
      taxa will provide important information on how to activate intrinsic mechanisms
      for successful brain regeneration in humans.

PMID- 19111626
TI  - Mechanisms of the cough associated with rhinosinusitis.
AB  - The diseases of the nose and paranasal sinuses (rhinosinusitis) often in
      combination with asthma and gastroesophageal reflux are common causes of chronic
      cough in patients with normal chest radiograph. The relationships between
      rhinosinusitis and cough are incompletely understood. We investigated modulation
      of the cough reflex by the inputs from the nose. We demonstrate that the cough
      reflex is sensitized by the intranasal administration of sensory nerve activators
      in animal models and in humans. Cough reflex is also sensitized in the guinea pig
      model of allergic nasal inflammation and in patients with allergic rhinitis. In
      patients with allergic rhinitis the cough sensitization is augmented during the
      allergen season. We conclude that the cough reflex can be sensitized from the
      nose. Our data indicate that this sensitization is mediated by nasal sensory
      nerves. We speculate that by inducing the cough reflex sensitization
      rhinosinusitis contributes to chronic cough. If combined with environmental or
      endogenous cough triggers, the cough reflex sensitization is predicted to cause
      excessive coughing. The potential endogenous cough triggers may be associated
      with rhinosinusitis (postnasal drip, aspiration of nasal secrets) or secondary to
      a coexistent disease such as asthma or gastroesophageal reflux.

PMID- 19111627
TI  - Toll-like receptor 4-dependent activation of myeloid dendritic cells by
      leukocidin of Staphylococcus aureus.
AB  - Leukocidin (Luk), an exotoxin of Staphylococcus aureus consisting of LukF and
      LukS, is a hetero-oligomeric pore-forming cytolytic toxin toward human and rabbit
      polymorphonuclear leukocytes. However, it is uncertain how Luk affects the host
      immune response. In the present study, we investigated whether Luk has the
      ability to stimulate mouse bone marrow-derived myeloid dendritic cells (BM-DCs).
      LukF activated BM-DCs to generate IL-12p40 mRNA, induce intracellular expression
      and extracellular secretion of this cytokine and express CD40 on their surface,
      whereas LukS showed a much lower or marginal ability in the activation of BM-DCs
      than its counterpart component. Similarly, TNF-alpha was secreted by BM-DCs upon
      stimulation with these components. Combined addition of these components did not
      lead to a further increase in IL-12p40 secretion. IL-12p40 production caused by
      LukF was completely abrogated in BM-DCs from TLR4-deficient mice similarly to the
      response to lipopolysaccharide (LPS). Polymixin B did not affect the LukF-induced
      IL-12p40 production, although the same treatment completely inhibited the LPS
      induced response. Boiling significantly inhibited the response caused by LukF,
      but not by LPS. Finally, in a luciferase reporter assay, LukF induced the
      activation of NF-kappaB in HEK293T cells transfected with TLR4, MD2 and CD14,
      whereas LukS did not show such activity. These results demonstrate that LukF
      caused the activation of BM-DCs by triggering a TLR4-dependent signaling pathway
      and suggests that Luk may affect the host inflammatory response as well as show a
      cytolytic effect on leukocytes.

PMID- 19111628
TI  - Mobilization of steryl esters from lipid particles of the yeast Saccharomyces
      cerevisiae.
AB  - In the yeast as in other eukaryotes, formation and hydrolysis of steryl esters
      (SE) are processes linked to lipid storage. In Saccharomyces cerevisiae, the
      three SE hydrolases Tgl1p, Yeh1p and Yeh2p contribute to SE mobilization from
      their site of storage, the lipid particles/droplets. Here, we provide evidence
      for enzymatic and cellular properties of these three hydrolytic enzymes. Using
      the respective single, double and triple deletion mutants and strains
      overexpressing the three enzymes, we demonstrate that each SE hydrolase exhibits
      certain substrate specificity. Interestingly, disturbance in SE mobilization also
      affects sterol biosynthesis in a type of feedback regulation. Sterol
      intermediates stored in SE and set free by SE hydrolases are recycled to the
      sterol biosynthetic pathway and converted to the final product, ergosterol. This
      recycling implies that the vast majority of sterol precursors are transported
      from lipid particles to the endoplasmic reticulum, where sterol biosynthesis is
      completed. Ergosterol formed through this route is then supplied to its
      subcellular destinations, especially the plasma membrane. Only a minor amount of
      sterol precursors are randomly distributed within the cell after cleavage from
      SE. Conclusively, SE storage and mobilization although being dispensable for
      yeast viability contribute markedly to sterol homeostasis and distribution.

PMID- 19111629
TI  - The cognitive and psychomotor effects of remacemide and carbamazepine in newly
      diagnosed epilepsy.
AB  - An international trial comparing remacemide hydrochloride with carbamazepine was
      undertaken in individuals with newly diagnosed epilepsy using a novel double
      blind, parallel-group, double triangular sequential design. Patients with two or
      more partial or generalized tonic-clonic seizures in the previous year were
      randomized to remacemide or carbamazepine and titrated to a target dose of 600
      mg/day. Subsequent dosage adjustments were allowed while maintaining the blind.
      Repeated assessments of neuropsychological function and mood were carried out
      using computerized and conventional measures. The trial was completed 20 months
      after initiation, following the second interim analysis. Efficacy as measured by
      seizure recurrence showed remacemide to be inferior to carbamazepine. Baseline
      cognitive and neuropsychological measures showed impairment across the whole
      patient population. Cognitive/neuropsychological performance at 8, 24, and 48
      weeks was compared with that at baseline. Significant deterioration was seen on
      measures of information processing speed and attention after treatment with
      carbamazepine. The study data provide evidence for the utility and sensitivity of
      a number of cognitive assessments, which may be employed in future trials of
      antiepileptic drugs.

PMID- 19111630
TI  - Large differences in the genome organization of different plant Trypanosomatid
      parasites (Phytomonas spp.) reveal wide evolutionary divergences between taxa.
AB  - All currently known plant trypanosomes have been grouped in the genus Phytomonas
      spp., although they can differ greatly in terms of both their biological
      properties and effects upon the host. Those parasitizing the phloem sap are
      specifically associated with lethal syndromes in Latin America, such as, phloem
      necrosis of coffee, 'Hartrot' of coconut and 'Marchitez sorpresiva' of oil palm,
      that inflict considerable economic losses in endemic countries. The genomic
      organization of one group of Phytomonas (D) considered as representative of the
      genus has been published previously. The present work presents the genomic
      structure of two representative isolates from the pathogenic phloem-restricted
      group (H) of Phytomonas, analyzed by pulsed field gel electrophoresis followed by
      hybridization with chromosome-specific DNA markers. It came as a surprise to
      observe an extremely different genomic organization in this group as compared
      with that of group D. Most notably, the chromosome number is 7 in this group
      (with a genome size of 10 Mb) versus 21 in the group D (totalling 25 Mb). These
      data unravel an unsuspected genomic diversity within plant trypanosomatids, that
      may justify a further debate about their division into different genera.

PMID- 19111631
TI  - Urinary CD20 mRNA as a surrogate of CD20-positive cells infiltration during
      allograft dysfunction in renal transplant patients.
AB  - B lymphocyte infiltration in renal acute allograft rejection has been associated
      with steroid resistance and poor outcomes. We aimed to measure CD20 mRNA in urine
      of renal transplant patients with graft dysfunction and correlate with the
      histological diagnosis and immunohistochemical (IH) staining for CD20. A total of
      48 urine samples were analyzed (21 with acute rejection, 10 with chronic
      allograft nephropathy, 11 with unspecific tubular lesions, 3 with acute
      pyelonephritis and 3 with polyomavirus nephropathy). Higher urinary CD20 levels
      associated with a positive IH staining for CD20 (>50 positive cells/HPF) in renal
      tissue (p=0.04), with a sensitivity of 83.3% and a specificity of 51.6%. Within
      the acute rejection group, a positive staining for CD20 was not associated with
      graft loss, steroid resistance or lack of return to basal creatinine after
      treatment, but was associated with higher serum creatinine at 3 and 6 months, 1
      and 2 years after the acute episode (p<0.05). In conclusion, we showed that
      urinary levels of CD20 detected by RT-PCR had a high sensitivity for CD20+
      staining in the corresponding renal tissue, but with a low specificity. Patients
      with clusters of CD20+ cells >50/HPF had higher serum creatinine after 2 years of
      follow up.

PMID- 19111632
TI  - Flavonol-rich RVHxR from Rhus verniciflua Stokes and its major compound fisetin
      inhibits inflammation-related cytokines and angiogenic factor in rheumatoid
      arthritic fibroblast-like synovial cells and in vivo models.
AB  - Rheumatoid arthritis (RA) is an aggressive inflammatory disease in which
      cytokines/chemokines are thought to recruit leukocytes and induce angiogenesis.
      The aim of this study is to investigate the effect of flavonol-rich residual
      layer of hexane fraction from Rhus verniciflua Stokes (RVHxR) and its major
      compound fisetin on inflammatory cytokine/chemokine production and angiogenic
      factor in IL-1beta-stimulated RA fibroblast-like synovial cells (FLS) and
      inflammatory in vivo models. Flavonol-rich RVHxR and its major compound fisetin
      significantly inhibited IL-1beta-induced FLS proliferation in a dose-dependent
      manner. Flavonol-rich RVHxR and fisetin significantly decreased IL-1beta-induced
      inflammatory cytokines (TNF-alpha, interleukin (IL)-6)/chemokines (IL-8, monocyte
      chemoattractant protein (MCP)-1), and vascular endothelial growth factor (VEGF)
      of RA FLS. Flavonol-rich RVHxR dose dependently diminished the phophorylation of
      extracellular signal regulated kinase (ERK) and phospho-Jun NH((2))-terminal
      kinase (JNK), and its down regulation induced by RVHxR at nontoxic
      concentrations, while activated the phosphorylation of p38 MAPK in IL-1beta
      stimulated RA FLS. The p38 specific inhibitor SB203580 cotreatment with RVHxR
      effectively increased the expression of VEGF and blocked the phosphorylation of
      p38 MAPK in IL-1beta-stimulated RA FLS, confirming a critical role of p38 MAPK
      pathway in angiogenesis inhibition. In experimental inflammation-related models,
      flavonol-rich RVHxR and fisetin have shown significant anti-inflammatory
      activities on vascular permeability, leukocyte migration and cellular immunity.
      Also, flavonol-rich RVHxR and fisetin treatments significantly reduced the
      incidence and severity of collagen-induced arthritis model. These results suggest
      that RVHxR and its major compound fisetin have shown potent suppressive effects
      on some inflammatory cytokines/chemokines and angiogenic factor in IL-1beta
      stimulated RA FLS and inflammatory in vivo models. We believe that flavonol-rich
      RVHxR is a potential therapeutic agent in the treatment of inflammatory and
      angiogenesis related diseases.

PMID- 19111633
TI  - Idiopathic diaphragmatic paralysis--satisfactory improvement of inspiratory
      muscle function by inspiratory muscle training.
AB  - Daily inspiratory muscle strength and endurance training (IMT) was performed in a
      44-year-old patient with idiopathic bilateral diaphragmatic paralysis (BDP) in
      addition to nocturnal non-invasive ventilation (NIV). After 4 months of training
      inspiratory muscle function improved satisfactorily whereas phrenic nerve latency
      remained pathological. Due to the improvement of inspiratory muscle capacity
      nocturnal NIV could be stopped without inducing nocturnal respiratory
      insufficiency.

PMID- 19111634
TI  - Elucidation of the substrate specificity, kinetic and catalytic mechanism of
      adenylosuccinate lyase from Plasmodium falciparum.
AB  - Adenylosuccinate lyase (ASL) catalyzes two distinct but chemically similar
      reactions in purine biosynthesis. The first, exclusive to the de novo pathway
      involves the cleavage of 5-aminoimidazole-4-(N-succinylcarboxamide)
      ribonucleotide (SAICAR) to 5-aminoimidazole-4-carboxamide ribonucleotide (AICAR)
      and fumarate and the second common to both de novo and the salvage pathways
      involves the cleavage of succinyl-adenosine monophosphate (SAMP) to AMP and
      fumarate. A detailed kinetic and catalytic mechanism of the recombinant His
      tagged ASL from Plasmodium falciparum (PfASL) is presented here. Initial velocity
      kinetics, product inhibition studies and transient kinetics indicate a Uni-Bi
      rapid equilibrium ordered mechanism. Substrate and solvent isotope effect studies
      implicate the process of C(gamma)-N bond cleavage to be rate limiting.
      Interestingly, the effect of pH on k(cat) and k(cat)/K(m) highlight ionization of
      the base only in the enzyme substrate complex and not in the enzyme alone,
      thereby implicating the pivotal role of the substrate in the activation of the
      catalytic base. Site-directed mutagenesis implicates a key role for the conserved
      serine (S298) in catalysis. Despite the absence of a de novo pathway for purine
      synthesis and most importantly, the absence of other enzymes that can metabolise
      AICAR in P. falciparum, PfASL catalyzes the SAICAR cleavage reaction with kinetic
      parameters similar to those of SAMP reaction and binds AICAR with affinity
      similar to that of AMP. The presence of this catalytic feature allows the use of
      AICAR or its analogues as inhibitors of PfASL and hence, as novel putative anti
      parasitic agents. In support of this, we do see a dose dependent inhibition of
      parasite growth in the presence of 5-aminoimidazole-4-carboxamide ribonucleoside
      (AICAriboside) with half-maximal inhibition at 167+/-5 microM.

PMID- 19111635
TI  - Serum 25-hydroxyvitamin D as an independent determinant of 1-84 PTH and bone
      mineral density in non-diabetic predialysis CKD patients.
AB  - The role of 25-hydroxyvitamin D [25(OH)D] and fibroblast growth factor-23 (FGF
      23) in chronic kidney disease-mineral and bone disorder (CKD-MBD) remains elusive
      in predialysis CKD patients. From the fact that FGF-23 suppresses bone
      mineralization in vitro and that 1alpha-hydroxylase is present in parathyroid
      cells and osteoblasts, they may be associated with bone mass or serum parathyroid
      hormone (PTH) level. In this cross-sectional observational study, we investigated
      the potential associations of 25(OH)D or FGF-23 with 1-84 PTH and bone mineral
      density (BMD) in the femoral neck (FN) and lumbar spine (LS) of 325 non-diabetic
      patients. All patients had stages 3-5 CKD and had never been treated with
      bisphosphonate, estrogen, or vitamin D. We measured bone-specific alkaline
      phosphatase (bone ALP), intact FGF-23 and 1-84 PTH in a third generation assay,
      and performed a multiple regression analysis for 1-84 PTH and BMD Z-score. In our
      cohort, 80.1% had 25(OH)D levels less than 30 ng/mL, and 4.1% had levels less
      than 15 ng/mL. A univariate analysis indicated a negative association for 25(OH)D
      with 1-84 PTH and bone ALP. A multivariate analysis showed that the significant
      determinants for 1-84 PTH were 25(OH)D, estimated glomerular filtration rate
      (eGFR), corrected calcium, serum calcitriol and phosphate. Intriguingly, the
      three former parameters had negative associations with 1-84 PTH while calcitriol
      had a positive association. While further adjustment of FGF-23 extinguished the
      positive association of phosphate and 1-84 PTH, there was absolutely no increase
      in the R2. With regard to the BMD Z-score, 25(OH)D and the body mass index were
      the significant common independent positive determinants for both FN and LS,
      whereas bone ALP was the negative determinant even though there was no
      correlation noted for 1-84 PTH, calcitriol, or FGF-23 with BMD. In addition, eGFR
      positively contributed to the Z-score only in FN. Therefore, despite a positive
      correlation between 25(OH)D and calcitriol, their contribution to the CKD-MBD
      appears to be different. Since the significant associations for 25(OH)D with 1-84
      PTH and BMD were independent of serum calcitriol and bone ALP, this might imply
      that 25(OH)D has a direct effect on the parathyroid gland and bone.

PMID- 19111636
TI  - Potential of Psidium guajava supplemented fish diets in controlling Aeromonas
      hydrophila infection in tilapia (Oreochromis niloticus).
AB  - Fourteen herbs were extracted in water, 95% ethanol, and ether, and tested in
      vitro for antimicrobial activities against Aeromonas hydrophila, a fish pathogen
      causing motile Aeromonas septicemia. Using swab paper disc assays and minimal
      inhibitory concentration (MIC) determinations, we noted that the ethanol extract
      of Psidium guajava leaf exhibited the strongest antimicrobial activity. The
      extract allowed growth-inhibited A. hydrophila cells to regrow in fresh BHI broth
      indicating a bacteriostatic mode of action. In a pathogenicity test, the median
      lethal dose (LD(50)) of A. hydrophila for tilapia (Oreochromis niloticus) by
      intraperitoneal injection was 3.44 x 10(6) CFU/ml. In vivo experiments showed
      that fish diets containing either dry leaf powder of P. guajava or dried ethanol
      extract of P. guajava leaf reduced mortality of A. hydrophila infected tilapia
      with no detected adverse effect on the fish. This study suggests that P. guajava
      leaf has the potential to control fish diseases caused by A. hydrophila.

PMID- 19111637
TI  - Effect of aeration on stabilization of organic solid waste and microbial
      population dynamics in lab-scale landfill bioreactors.
AB  - This study investigated microbial population dynamics and performance in lab
      scale conventional, anaerobic, and aerobic landfill bioreactors specialized for
      high-organic wastes. Each reactor (2.35 l) was loaded with 1.5 kg of organic
      solid waste made of sludge cake, dry dog food, and wood chips. The conventional
      reactor was operated without leachate recirculation and aeration, but the other
      reactors used leachate recirculation at 200 ml/d and without aeration (anaerobic
      bioreactor) or with aeration at 2 l/min (aerobic bioreactor). The respective
      final waste volumes on day 138 of the conventional, anaerobic, and aerobic
      reactors were approximately 75%, 65%, and 60% of the initial volumes. Leachate
      recirculation in the anaerobic bioreactor accelerated biochemical reactions and
      promoted methane production. However, leachate from the anaerobic bioreactor
      showed TOC and NH(4)(+)-N concentrations that were as high as those of the
      conventional reactor. Aeration lowered leachate production and methane
      concentration and decreased organic matter in solid waste and leachate.
      Furthermore, the MPN value of amoA gene reached 10(5) MPN-copies/g-dry in the
      aerobic bioreactor, where nitrogen was removed from organic solid waste and
      leachate. During the first 72 d, the aerobic bioreactor's MPN value of fungal 18S
      rDNA was the highest among reactors, but it decreased gradually. All reactors
      showed similar MPN values of eubacterial 16S rDNA, nirS, and nirK.

PMID- 19111638
TI  - Partial nitritation of raw anaerobic sludge digester liquor by swim-bed and swim
      bed activated sludge processes and comparison of their sludge characteristics.
AB  - This study evaluated performance of swim-bed (SB) reactors packed with a novel
      acrylic fiber carrier (BF) and swim-bed activated sludge (SBAS) reactor for
      partial nitritation of anaerobic sludge digester liquor from a municipal
      wastewater treatment plant. Comparison of characteristics of sludge obtained from
      both the reactors was also made. The average conversion rates of ammonium to
      nitrite were 52.3% and 40.0% under relatively high nitrogen loading rates over
      3.0 kg-N/m(3)/d, respectively in two reactors. The average BOD(5) removal
      efficiencies were 74.3% and 64.4%, respectively in the two reactors. The size of
      the sludge pellets taken from SB and SBAS reactors was found to be approximately
      three times (229 mum versus 88 mum) of that of the seed sludge. This sludge also
      had relatively high extracellular proteins levels indicating better sludge
      settling capability as compared to the sludge taken from SBAS reactor. Although
      the effluent nitrite/ammonium ratios had fluctuated in both reactor in some
      extent, the low dissolved oxygen concentration (average of 2.5 versus 0.35 mg/l),
      low suspended solids (average of 33.3 versus 33.5 mg/l), and about 50% ammonium
      conversion to nitrite demonstrated the application potential of anammox process
      for nitrogen removal.

PMID- 19111639
TI  - Cancer DNA microarray analysis considering multi-subclass with graph-based
      clustering method.
AB  - It is well known that various genes related to cell cycle, cell-cell adhesion,
      and transcriptional regulation cause the onset of cancer. Moreover, environmental
      factors including age, sex, and lifestyle can also contribute to the onset of
      cancer. Therefore, it is difficult to ascertain which factors influence the
      onset. Thus, patients suffering from same disease can be divided into several
      distinct groups. In the present study, we applied graph-based clustering to
      several DNA microarray datasets before the classification analysis. Several
      clusters formed by the graph-based clustering were used for the construction of
      multi-class classification model with the k-nearest neighbor and for finding
      genes, which are specific to a certain cluster, by One vs. Others classification.
      Using this approach, the classification model was constructed for four microarray
      datasets, leukemia, breast cancer, prostate cancer, and colon cancer, and the
      accuracies of classification with k-nearest neighbor were all more than 80%. And
      in the breast cancer dataset, we succeeded in finding genes that are specific in
      a cluster consisting of 38 control group samples. These results indicate the
      importance of sample clustering before classification model construction.

PMID- 19111640
TI  - Characterization of gene encoding amylopullulanase from plant-originated lactic
      acid bacterium, Lactobacillus plantarum L137.
AB  - A starch-hydrolyzing lactic acid bacterium, Lactobacillus plantarum L137, was
      isolated from traditional fermented food made from fish and rice in the
      Philippines. A gene (apuA) encoding an amylolytic enzyme from Lactobacillus
      plantarum L137 was cloned, and its nucleotide sequence was determined. The apuA
      gene consisted of an open reading frame of 6171 bp encoding a protein of 2056
      amino acids, the molecular mass of which was calculated to be 215,625 Da. The
      catalytic domains of amylase and pullulanase were located in the same region
      within the middle of the N-terminal region. The deduced amino acid sequence
      revealed four highly conserved regions that are common among amylolytic enzymes.
      In the N-terminal region, a six-amino-acid sequence (Asp-Ala/Thr-Ala-Asn-Ser-Thr)
      is repeated 39 times, and a three-amino-acid sequence (Gln-Pro-Thr) is repeated
      50 times in the C-terminal region. The apuA gene was subcloned in L. plantarum
      NCL21, which is a plasmid-cured derivative of the wild-type L137 strain and has
      no amylopullulanase activity, and the gene was overexpressed under the control of
      its own promoter. The ApuA enzyme from this recombinant L. plantarum NCL21
      harboring apuA gene was purified. The enzyme has both alpha-amylase and
      pullulanase activities. The N-terminal sequence of the purified enzyme showed
      that the signal peptide was cleaved at Ala(36) and the molecular mass of the
      mature extracellular enzyme is 211,537 Da. The major reaction products from
      soluble starch were maltotriose (G3) and maltotetraose (G4). Only maltotriose
      (G3) was produced from pullulan. From these results, we concluded that ApuA is an
      amylolytic enzyme belonging to the amylopullulanase family.

PMID- 19111641
TI  - Synthesis of 4-pyridoxolactone from pyridoxine using a combination of transformed
      Escherichia coli cells.
AB  - We developed a simple and efficient synthesis for 4-pyridoxolactone starting with
      pyridoxine and using a whole-cell biotransformation by two transformed
      Escherichia coli cell types. One set of transformed cells expressed pyridoxine 4
      oxidase, catalase, and chaperonin, while the second set expressed pyridoxal 4
      dehydrogenase. With this combination of cells, pyridoxine was first oxidized to
      pyridoxal, which was then dehydrogenated to 4-pyridoxolactone by pyridoxine 4
      oxidase and pyridoxal 4-dehydrogenase, respectively. In a reaction mixture
      containing the two transformed cell types, 10 mM of pyridoxine was completely
      converted into 4-pyridoxolactone at 30 degrees C in 24 h. When starting with 80
      mM of pyridoxine, it was necessary to add 0.5 mM or more of NAD(+) to complete
      the reaction.

PMID- 19111642
TI  - Construction of a citrinin gene cluster expression system in heterologous
      Aspergillus oryzae.
AB  - Filamentous fungi are considered an attractive resource for the discovery and
      production of bioactive compounds. To facilitate molecular breeding, biosynthetic
      genes must be rapidly identified. But, even after the chemical structure of a
      compound is identified, finding the corresponding biosynthetic genes in the
      fungal genome still remains a challenge. In an attempt to overcome this
      difficulty and to easily characterize each gene in a cluster, we constructed a
      heterologous expression system using Aspergillus oryzae. The approximate region
      covering the citrinin biosynthetic gene cluster from Monascus purpureus was
      introduced into A. oryzae via an Aspergillus-Escherichia coli shuttle cosmid
      vector without manipulating the gene structure. The transformants showed slight
      but reproducible citrinin production and definite transcription of the
      biosynthetic genes. Introducing additional copies of an activator gene (ctnA),
      controlled by the Aspergillus nidulans trpC promoter, into the citrinin-cluster
      containing transformants enhanced the transcription of all the genes in the
      cluster and resulted in an almost 400-fold higher citrinin production compared to
      that of the parental transformant. This result suggested that CtnA controlled
      citrinin production in this system in the same way as in the native strain. This
      is the first report documenting the heterologous production of functional fungal
      secondary metabolites in A. oryzae following the introduction of an entire gene
      cluster.

PMID- 19111644
TI  - Efficient dye decolorization and production of dye decolorizing enzymes by the
      basidiomycete Thanatephorus cucumeris Dec 1 in a liquid and solid hybrid culture.
AB  - Thanatephorus cucumeris Dec 1, a basidiomycete, is a promising decomposer of
      several xenobiotics. Air-membrane surface bioreactor culture (AMS culture), a
      hybrid between solid-state and submerged culture, was used for Dec 1 growth. The
      optimum temperature for AMS culture (25 degrees C) was lower than that for
      submerged culture (30 degrees C). Fungal growth was almost the same in AMS
      culture as in submerged culture at optimum temperatures. However, protein
      secretion, dye decolorizing peroxidase (DyP) activity, and aryl alcohol oxidase
      activity, were 18-, 233-, and 36.5-fold higher in AMS culture than in submerged
      culture, respectively, indicating that AMS culture of Dec 1 was superior to
      submerged culture. In in vivo dye decolorization tests, 13 of 16 dyes were
      decolorized by more than 90% within 10 days. Interestingly, under AMS culture, a
      biofilm was formed; biofilm formation was not, however, essential for DyP and
      manganese dependent peroxidase (MnP) activities. Although the correlation between
      DyP activity and water activity was unclear, MnP activity seemed to increase in
      activity with decreasing water activity, even when no biofilm formation was
      observed.

PMID- 19111643
TI  - Direct production of L-tagatose from L-psicose by Enterobacter aerogenes 230S.
AB  - L-tagatose was produced directly from L-psicose by subjecting the same biomass
      suspension to microbial reduction followed by oxidation using a newly isolated
      bacteria Enterobacter aerogenes 230S. After various optimizations, it was
      observed that cells grown on xylitol have the best conversion potential.
      Moreover, E. aerogenes 230S converted L-psicose to L-tagatose at a faster rate in
      the presence of polyols such as glycerol, D-sorbitol, ribitol, L-arabitol, D
      mannitol and xylitol. At 5% substrate concentration, the conversion ratio of L
      psicose to L-tagatose was above 60% in the presence of glycerol. Identity of
      crystalline L-tagatose was confirmed by HPLC analysis, (13)C-NMR spectra, and
      optical rotation.

PMID- 19111645
TI  - Isolation of industrial strains of Aspergillus oryzae lacking ferrichrysin by
      disruption of the dffA gene.
AB  - Based on studies using laboratory strains, the efficiency of gene disruption in
      Aspergillus oryzae, commonly known as koji mold, is low; thus, gene disruption
      has rarely been applied to the breeding of koji mold. To evaluate the efficiency
      of gene disruption in industrial strains of A. oryzae, we produced ferrichrysin
      biosynthesis gene (dffA) disruptants using three different industrial strains as
      hosts. PCR analysis of 438 pyrithiamine-resistant transformants showed dffA gene
      disruption efficiency of 42.9%-64.1%, which is much higher than previously
      reported. Analysis of the physiological characteristics of the disruptants
      indicated that dffA gene disruption results in hypersensitivity to hydrogen
      peroxide. To investigate the industrial characteristics of dffA gene disruptants,
      two strains were used to make rice koji and their properties were compared to
      those of the host strains. No differences were found between the dffA gene
      disruptants and the host strains, except that the disruptants did not produce
      ferrichrysin. Thus, this gene disruption technique is much more effective than
      conventional mutagenesis for A. oryzae breeding.

PMID- 19111646
TI  - Expression of the bacterial hemoglobin gene from Vitreoscilla stercoraria
      increases rifamycin B production in Amycolatopsis mediterranei.
AB  - It is well known that the culture for rifamycin B production by Amycolatopsis
      mediterranei requires high levels of dissolved oxygen, particularly in industrial
      processes. In this study, we report the construction of a vector for the
      expression of the bacterial hemoglobin gene (vhb) from Vitreoscilla stercoraria
      in a rifamycin B-overproducing strain of A. mediterranei. The effect was
      evaluated in the presence and absence of barbital. The vhb gene was cloned under
      the control of the PermE promoter, the Amycolatopsis lactamdurans plasmid pULVK2
      origin of replication, the kanamycin-resistant gene (Km), the erythromycin
      resistant gene (ermE) for selection, and ColE1. Industrial fermentation
      conditions were simulated in shake-flask cultures. Under low aeration, the
      transformed A. mediterranei strain with the vhb gene showed a 13.9% higher
      production of rifamycin B in a culture with barbital compared with the parental
      strain, and 29.5% higher production under the same conditions without barbital.

PMID- 19111647
TI  - Aerobic denitrification of Pseudomonas putida AD-21 at different C/N ratios.
AB  - An aerobic denitrifier was newly isolated from soil and its denitrification
      activity under different C/N (carbon/nitrogen) ratios was investigated. The
      isolate was identified as Pseudomonas putida AD-21 by biochemical studies and 16s
      rDNA sequencing analysis. P. putida AD-21 tolerated oxygen levels of 5.0-6.0
      mg/l. An (15)NH(4)/(14)NO(3) analysis indicated that the nitrogen of NH(4) was
      preferentially assimilated into the cell mass and that the nitrate removed could
      be considered an indication of bacterial denitrification efficiency. Increasing
      the C/N ratio increased the nitrate removal rates, whereas nitrogen assimilation
      into the cell mass was not affected. The optimal C/N ratio was 8 with a maximum
      nitrate removal rate of 254.6 mg/l/h and a nitrate removal efficiency of 95.9%.
      The results suggest that P. putida AD-21 may be a good candidate for aerobic
      wastewater treatment.

PMID- 19111648
TI  - Renaturation of lysozyme with a protein disulfide isomerase chaperone results in
      enzyme super activity.
AB  - When the oxidative refolding of lysozyme (Lyzm) was carried out in the presence
      of protein disulfide isomerase (PDI) an increased refolding rate and a recovered
      activity exceeding 100% were reproducibly observed. The origin of this excess
      activity was investigated by HPLC, SDS-PAGE, and mass spectrometry and assessed
      using an assay for Lyzm activity. The refolding of Lyzm was achieved through the
      formation of PDI-Lyzm intermediates and the excess activity was derived from the
      nascent lysozyme released from these complexes. The released lysozyme exhibited a
      higher molecular activity than observed for the native protein.

PMID- 19111649
TI  - Genome-wide analysis of the effects of location and number of stress response
      elements on gene expression in Saccharomyces cerevisiae.
AB  - We analyzed the effects of the location and number of stress response elements
      (STREs) on gene expression in Saccharomyces cerevisiae. Genes containing STRE
      between 51 and 300 bp upstream from translational start codon tended to be up
      regulated and genes with multiple STREs exhibited higher up-regulation under
      stress conditions.

PMID- 19111650
TI  - A novel enzymatic method for measuring mizoribine 5'-monophosphate levels in
      serum.
AB  - Inosine 5'-monophosphate dehydrogenases (IMPDH) from Oceanobacillus iheyensis and
      Bacillus subtilis were biochemically characterized with the aim of establishing a
      mizoribine 5'-monophosphate (MZR-P) assay. MZR-P is the active metabolite of
      mizoribine, which has been successfully used as an immunosuppressive agent. A
      sensitive method for measuring the MZR-P concentration in serum, based on its
      ability to inhibit IMPDH, was developed. The method was applied to an automatic
      clinical analyzer, enabling measurement of MZR-P levels in a set of serum
      samples. MZR-P at concentrations of 0.1-13.6 (microg/ml (0.3-40 microM) in the
      samples could be measured with 0.7% within-run coefficients of variation.

PMID- 19111651
TI  - Transcription by moonlight: structural basis of an extraribosomal activity of
      ribosomal protein S10.
AB  - In this issue of Molecular Cell, Luo et al. (2008) show that S10 protein can
      function in the ribosome or the transcript elongation complex with minimal
      structural change, providing new insights into the roles of S10 and NusB in
      transcript elongation.

PMID- 19111652
TI  - YAP and p73: a complex affair.
AB  - In this issue of Molecular Cell, Lapi et al. (2008) demonstrate that YAP binds
      p73 to activate PML transcription, which in turn mediates YAP sumoylation and
      stabilization, increases p73 activity, and thereby generates a DNA-damage-induced
      feedback loop.

PMID- 19111653
TI  - A new window onto translational repression by bacterial sRNAs.
AB  - In this issue of Molecular Cell, Bouvier et al. (2008) show that bacterial sRNAs
      can repress mRNA translation not only by binding to the Shine-Dalgarno element
      but also by base pairing anywhere within the first few codons of the protein
      coding region.

PMID- 19111654
TI  - Nucleolar dominance and DNA methylation directed by small interfering RNA.
AB  - In the December 5th issue of Molecular Cell, Preuss et al. (2008) demonstrated a
      link between small interfering RNA (siRNA)-directed de novo DNA methylation and
      rDNA silencing in nucleolar dominance.

PMID- 19111655
TI  - Found in translation: another RNA helicase function.
AB  - In a recent issue of Cell, Pisareva et al. (2008) reveal that DHX29, a previously
      uncharacterized mammalian DExH-box protein, facilitates translation initiation on
      mRNAs with structured 5' untranslated regions.

PMID- 19111656
TI  - Regulated proteolysis of DNA polymerase eta during the DNA-damage response in C.
      elegans.
AB  - Both the POLH-1 (pol eta) translesion synthesis (TLS) DNA polymerase and the GEI
      17 SUMO E3 ligase are essential for the efficient replication of damaged
      chromosomes in Caenorhabditis elegans embryos. Here we study how POLH-1 is
      regulated during a DNA-damage response in these embryos. We report that DNA
      damage triggers the degradation of POLH-1 and that degradation is mediated by the
      Cul4-Ddb1-Cdt2 (CRL4-Cdt2) pathway that has previously been shown to degrade the
      replication factor Cdt1 during S phase. We also show that GEI-17 protects POLH-1
      from CRL4-Cdt2-mediated destruction until after it has performed its function in
      TLS, and this is likely via SUMOylation of POLH-1. These studies reveal that POLH
      1 undergoes DNA-damage-induced proteolysis and that GEI-17 regulates the timing
      of this proteolysis. Implications for how this system may control the removal of
      POLH-1 from replication forks after TLS are discussed.

PMID- 19111657
TI  - Mechanistic insight into site-restricted monoubiquitination of FANCD2 by Ube2t,
      FANCL, and FANCI.
AB  - A key step in the Fanconi anemia (FA) tumor suppressor pathway is the site
      specific monoubiquitination of the FANCD2 protein. Genetic studies indicate that
      this crucial modification requires eight known FA gene products and the E2
      conjugating enzyme Ube2t. Here, we minimally reconstitute this monoubiquitination
      reaction with Ube2t and the FANCL protein, revealing that monoubiquitination is
      stimulated by a conserved RWD-like domain in FANCL. Furthermore, addition of the
      FANCI protein enhances monoubiquitination and also restricts it to the in vivo
      substrate lysine residue on FANCD2. This work therefore establishes a system that
      provides mechanistic insight into the functions of FANCL and FANCI in the
      catalysis of FANCD2 monoubiquitination.

PMID- 19111658
TI  - HP1 proteins form distinct complexes and mediate heterochromatic gene silencing
      by nonoverlapping mechanisms.
AB  - HP1 proteins are a highly conserved family of eukaryotic proteins that bind to
      methylated histone H3 lysine 9 (H3K9) and are required for heterochromatic gene
      silencing. In fission yeast, two HP1 homologs, Swi6 and Chp2, function in
      heterochromatic gene silencing, but their relative contribution to silencing
      remains unknown. Here we show that Swi6 and Chp2 exist in nonoverlapping
      complexes and make distinct contributions to silencing. Chp2 associates with the
      SHREC histone deacetylase complex (SHREC2), is required for histone H3 lysine 14
      (H3K14) deacetylation, and mediates transcriptional repression by limiting RNA
      polymerase II access to heterochromatin. In contrast, Swi6 associates with a
      different set of nuclear proteins and with noncoding centromeric transcripts and
      is required for efficient RNAi-dependent processing of these transcripts. Our
      findings reveal an unexpected role for Swi6 in RNAi-mediated gene silencing and
      suggest that different HP1 proteins ensure full heterochromatic gene silencing
      through largely nonoverlapping inhibitory mechanisms.

PMID- 19111659
TI  - Structural and functional analysis of the E. coli NusB-S10 transcription
      antitermination complex.
AB  - Protein S10 is a component of the 30S ribosomal subunit and participates together
      with NusB protein in processive transcription antitermination. The molecular
      mechanisms by which S10 can act as a translation or a transcription factor are
      not understood. We used complementation assays and recombineering to delineate
      regions of S10 dispensable for antitermination, and determined the crystal
      structure of a transcriptionally active NusB-S10 complex. In this complex, S10
      adopts the same fold as in the 30S subunit and is blocked from simultaneous
      association with the ribosome. Mass spectrometric mapping of UV-induced
      crosslinks revealed that the NusB-S10 complex presents an intermolecular,
      composite, and contiguous binding surface for RNAs containing BoxA
      antitermination signals. Furthermore, S10 overproduction complemented a nusB null
      phenotype. These data demonstrate that S10 and NusB together form a BoxA-binding
      module, that NusB facilitates entry of S10 into the transcription machinery, and
      that S10 represents a central hub in processive antitermination.

PMID- 19111660
TI  - PML, YAP, and p73 are components of a proapoptotic autoregulatory feedback loop.
AB  - p73 has been identified as a structural and functional homolog of the tumor
      suppressor p53. The transcriptional coactivator Yes-associated protein (YAP) has
      been demonstrated to interact with and to enhance p73-dependent apoptosis in
      response to DNA damage. Here, we show the existence of a proapoptotic
      autoregulatory feedback loop between p73, YAP, and the promyelocytic leukemia
      (PML) tumor suppressor gene. We demonstrate that PML is a direct transcriptional
      target of p73/YAP, and we show that PML transcriptional activation by p73/YAP is
      under the negative control of the proto-oncogenic Akt/PKB kinase. Importantly, we
      find that PML and YAP physically interact through their PVPVY and WW domains,
      respectively, causing PML-mediated sumoylation and stabilization of YAP. Hence,
      we determine a mechanistic pathway in response to DNA damage that could have
      relevant implications for the treatment of human cancer.

PMID- 19111661
TI  - A fence-like coat for the nuclear pore membrane.
AB  - We recently proposed a cylindrical coat for the nuclear pore membrane in the
      nuclear pore complex (NPC). This scaffold is generated by multiple copies of
      seven nucleoporins. Here, we report three crystal structures of the nucleoporin
      pair Seh1*Nup85, which is part of the coat cylinder. The Seh1*Nup85 assembly
      bears resemblance in its shape and dimensions to that of another nucleoporin
      pair, Sec13*Nup145C. Furthermore, the Seh1*Nup85 structures reveal a hinge motion
      that may facilitate conformational changes in the NPC during import of integral
      membrane proteins and/or during nucleocytoplasmic transport. We propose that
      Seh1*Nup85 and Sec13*Nup145C form 16 alternating, vertical rods that are
      horizontally linked by the three remaining nucleoporins of the coat cylinder.
      Shared architectural and mechanistic principles with the COPII coat indicate a
      common evolutionary origin and support the notion that the NPC coat represents
      another class of membrane coats.

PMID- 19111662
TI  - Small RNA binding to 5' mRNA coding region inhibits translational initiation.
AB  - Small noncoding RNAs (sRNAs) have predominantly been shown to repress bacterial
      mRNAs by masking the Shine-Dalgarno (SD) or AUG start codon sequence, thereby
      preventing 30S ribosome entry and, consequently, translation initiation. However,
      many recently identified sRNAs lack obvious SD and AUG complementarity,
      indicating that sRNA-mediated translational control could also take place at
      other mRNA sites. We report that Salmonella RybB sRNA represses ompN mRNA
      translation by pairing with the 5' coding region. Results of systematic antisense
      interference with 30S binding to ompN and unrelated mRNAs suggest that sRNAs can
      act as translational repressors by sequestering sequences within the mRNA down to
      the fifth codon, even without SD and AUG start codon pairing. This "five codon
      window" for translational control in the 5' coding region of mRNA not only has
      implications for sRNA target predictions but might also apply to cis-regulatory
      systems such as RNA thermosensors and riboswitches.

PMID- 19111664
TI  - Structure of a complete integrin ectodomain in a physiologic resting state and
      activation and deactivation by applied forces.
AB  - The complete ectodomain of integrin alpha(IIb)beta(3) reveals a bent, closed, low
      affinity conformation, the beta knee, and a mechanism for linking cytoskeleton
      attachment to high affinity for ligand. Ca and Mg ions in the recognition site,
      including the synergistic metal ion binding site (SyMBS), are loaded prior to
      ligand binding. Electrophilicity of the ligand-binding Mg ion is increased in the
      open conformation. The beta(3) knee passes between the beta(3)-PSI and alpha(IIb)
      knob to bury the lower beta leg in a cleft, from which it is released for
      extension. Different integrin molecules in crystals and EM reveal breathing that
      appears on pathway to extension. Tensile force applied to the extended ligand
      receptor complex stabilizes the closed, low-affinity conformation. By contrast,
      an additional lateral force applied to the beta subunit to mimic attachment to
      moving actin filaments stabilizes the open, high-affinity conformation. This
      mechanism propagates allostery over long distances and couples cytoskeleton
      attachment of integrins to their high-affinity state.

PMID- 19111663
TI  - Small-molecule inhibitors of HIF-2a translation link its 5'UTR iron-responsive
      element to oxygen sensing.
AB  - Cells transiently adapt to hypoxia by globally decreasing protein translation.
      However, specific proteins needed to respond to hypoxia evade this translational
      repression. The mechanisms of this phenomenon remain unclear. We screened for and
      identified small molecules that selectively decrease HIF-2a translation in an
      mTOR-independent manner, by enhancing the binding of Iron-Regulatory Protein 1
      (IRP1) to a recently reported iron-responsive element (IRE) within the 5'
      untranslated region (UTR) of the HIF-2a message. Knocking down the expression of
      IRP1 by shRNA abolished the effect of the compounds. Hypoxia derepresses HIF-2a
      translation by disrupting the IRP1-HIF-2a IRE interaction. Thus, this chemical
      genetic analysis describes a molecular mechanism by which translation of the HIF
      2a message is maintained during conditions of cellular hypoxia through inhibition
      of IRP-1-dependent repression. It also provides the chemical tools for studying
      this phenomenon.

PMID- 19111665
TI  - The role of Dbf4/Drf1-dependent kinase Cdc7 in DNA-damage checkpoint control.
AB  - The Dbf4/Drf1-dependent S-phase-promoting kinase Cdc7 (Ddk) is thought to be an
      essential target inactivated by the S-phase checkpoint machinery that inhibits
      DNA replication. However, we show here that the complex formation, chromatin
      association, and kinase activity of Ddk are not inhibited during the DNA-damage
      induced S-phase checkpoint response in Xenopus egg extracts and mammalian cells.
      Instead, we find that Ddk plays an active role in regulating S-phase checkpoint
      signaling. Addition of purified Ddk to Xenopus egg extracts or overexpression of
      Dbf4 in HeLa cells downregulates ATR-Chk1 checkpoint signaling and overrides the
      inhibition of DNA replication and cell-cycle progression induced by DNA-damaging
      agents. These results indicate that Ddk functions as an upstream regulator to
      monitor S-phase checkpoint signaling. We propose that Ddk modulates the S-phase
      checkpoint control by attenuating checkpoint signaling and triggering DNA
      replication reinitiation during the S-phase checkpoint recovery.

PMID- 19111666
TI  - Defining the glycan destruction signal for endoplasmic reticulum-associated
      degradation.
AB  - The endoplasmic reticulum (ER) must target potentially toxic misfolded proteins
      for retrotranslocation and proteasomal degradation while avoiding destruction of
      productive folding intermediates. For luminal proteins, this discrimination
      typically depends not only on the folding status of a polypeptide, but also on
      its glycosylation state. Two putative sugar binding proteins, Htm1p and Yos9p,
      are required for degradation of misfolded glycoproteins, but the nature of the
      glycan degradation signal and how such signals are generated and decoded remains
      unclear. Here we characterize Yos9p's oligosaccharide-binding specificity and
      find that it recognizes glycans containing terminal alpha1,6-linked mannose
      residues. We also provide evidence in vivo that a terminal alpha1,6-linked
      mannose-containing oligosaccharide is required for degradation and that Htm1p
      acts upstream of Yos9p to mediate the generation of such sugars. This strategy of
      marking potential substrates by Htm1p and decoding the signal by Yos9p is well
      suited to provide a proofreading mechanism that enhances substrate specificity.

PMID- 19111668
TI  - An approach based on liquid chromatography/electrospray ionization-mass
      spectrometry to detect diol metabolites as biomarkers of exposure to styrene and
      1,3-butadiene.
AB  - Styrene and 1,3-butadiene are important intermediates used extensively in the
      plastics industry. They are metabolized mainly through cytochrome P450-mediated
      oxidation to the corresponding epoxides, which are subsequently converted to
      diols by epoxide hydrolase or through spontaneous hydration. The resulting
      styrene glycol and 3-butene-1,2-diol have been suggested as biomarkers of
      exposure to styrene and 1,3-butadiene, respectively. Unfortunately, poor
      ionization of the diols within electrospray mass spectrometers becomes an
      obstacle to the detection of the two diols by liquid chromatography/electrospray
      ionization-mass spectrometry (LC/ESI-MS). We developed an LC/ESI-MS approach to
      analyze styrene glycol and 3-butene-1,2-diol by means of derivatization with 2
      bromopyridine-5-boronic acid (BPBA), which not only dramatically increases the
      sensitivity of diol detection but also facilitates the identification of the
      diols. The analytical approach developed was simple, quick, and convincing
      without the need for complicated chemical derivatization. To evaluate the
      feasibility of BPBA as a derivatizing reagent of diols, we investigated the
      impact of diol configuration on the affinity of a selection of diols to BPBA
      using the established LC/ESI-MS approach. We found that both cis and trans diols
      can be derivatized by BPBA. In conclusion, BPBA may be used as a general
      derivatizing reagent for the detection of vicinal diols by LC/MS.

PMID- 19111667
TI  - A library of yeast transcription factor motifs reveals a widespread function for
      Rsc3 in targeting nucleosome exclusion at promoters.
AB  - The sequence specificity of DNA-binding proteins is the primary mechanism by
      which the cell recognizes genomic features. Here, we describe systematic
      determination of yeast transcription factor DNA-binding specificities. We
      obtained binding specificities for 112 DNA-binding proteins representing 19
      distinct structural classes. One-third of the binding specificities have not been
      previously reported. Several binding sequences have striking genomic
      distributions relative to transcription start sites, supporting their biological
      relevance and suggesting a role in promoter architecture. Among these are Rsc3
      binding sequences, containing the core CGCG, which are found preferentially
      approximately 100 bp upstream of transcription start sites. Mutation of RSC3
      results in a dramatic increase in nucleosome occupancy in hundreds of proximal
      promoters containing a Rsc3 binding element, but has little impact on promoters
      lacking Rsc3 binding sequences, indicating that Rsc3 plays a broad role in
      targeting nucleosome exclusion at yeast promoters.

PMID- 19111669
TI  - Application of electrochemical properties of ordered mesoporous carbon to the
      determination of glutathione and cysteine.
AB  - In this study, the electrochemical activity of ordered mesoporous carbon (OMC)
      was investigated and applied to the determination of glutathione (GSH) and
      cysteine (CySH). It has been demonstrated that the ordered mesostructure of OMC
      has an important role in the electrocatalytic activity towards thiols, and the
      destruction of this structure results in the decrease of such properties. The
      electrochemical behavior of GSH at an OMC electrode was also investigated. The
      results showed that the process of oxidation of GSH at the OMC electrode is
      differs from that of CySH at the same electrode by the peak at 0.47V associated
      with CySH. This difference helped to reduce the interference of GSH during the
      determination of CySH in the presence of GSH. A sensor for the two thiols was
      developed with acceptable sensitivity and detection limits in a large
      determination range. These results obtained in the physiological medium and in
      the physiological levels of GSH and CySH, suggest that OMC is a promising
      material in the detection of thiols in biologically relevant experimental
      conditions (in terms of pH).

PMID- 19111670
TI  - Antiproliferative activity and apoptosis-inducing mechanism of Concanavalin A on
      human melanoma A375 cells.
AB  - The objective of this study was to investigate the antiproliferative activity and
      apoptosis-inducing mechanism of Concanavalin A (ConA) on human melanoma A375
      cells. We firstly simulated the three-dimensional structure of ConA.
      Subsequently, we found that ConA possessed remarkable antiproliferative effect on
      A375 cells. Further experimental data indicated that there was a link between its
      hemagglutinating activity, mannose-binding activity and antiproliferative
      activity. In addition, we showed that ConA induced A375 cell apoptosis in a
      caspase-dependent manner. Then, we demonstrated that the treatment of ConA caused
      mitochondrial transmembrane potential (MMP) collapse, cytochrome c release and
      caspase activation. In conclusion, we report for the first time that there may be
      a close correlation between carbohydrate-binding activity of ConA and its
      antiproliferative activity. Also, we demonstrate firstly that ConA induces A375
      cell death in a caspase-dependent manner as well as through a mitochondrial
      apoptotic pathway.

PMID- 19111671
TI  - Cartilage stress-relaxation proceeds slower at higher compressive strains.
AB  - Articular cartilage is the connective tissue which covers bone surfaces and
      deforms during in vivo activity. Previous research has investigated flow
      dependent cartilage viscoelasticity, but relatively few studies have investigated
      flow-independent mechanisms. This study investigated polymer dynamics as an
      explanation for the molecular basis of flow-independent cartilage
      viscoelasticity. Polymer dynamics predicts that stress-relaxation will proceed
      more slowly at higher volumetric concentrations of polymer. Stress-relaxation
      tests were performed on cartilage samples after precompression to different
      strain levels. Precompression increases the volumetric concentration of cartilage
      biopolymers, and polymer dynamics predicts an increase in relaxation time
      constant. Stress-relaxation was slower for greater precompression. There was a
      significant correlation between the stress-relaxation time constant and cartilage
      volumetric concentration. Estimates of the flow-dependent timescale suggest that
      flow-dependent relaxation occurs on a longer timescale than presently observed.
      These results are consistent with polymer dynamics as a mechanism of cartilage
      viscoelasticity.

PMID- 19111672
TI  - Novel channels of the inner mitochondrial membrane.
AB  - Along with a large number of carriers, exchangers and "pumps", the inner
      mitochondrial membrane contains ion-conducting channels which endow it with
      controlled permeability to small ions. Some have been shown to be the
      mitochondrial counterpart of channels present also in other cellular membranes.
      The manuscript summarizes the current state of knowledge on the major inner
      mitochondrial membrane channels, properties, identity and proposed functions.
      Considerable attention is currently being devoted to two K(+)-selective channels,
      mtK(ATP) and mtBK(Ca). Their activation in "preconditioning" is considered by
      many to underlie the protection of myocytes and other cells against subsequent
      ischemic damage. We have recently shown that in apoptotic lymphocytes inner
      membrane mtK(V)1.3 interacts with the pro-apoptotic protein Bax after the latter
      has inserted into the outer mitochondrial membrane. Whether the just-discovered
      mtIK(Ca) has similar cellular role(s) remains to be seen. The Ca(2+) "uniporter"
      has been characterized electrophysiologically, but still awaits a molecular
      identity. Chloride-selective channels are represented by the 107 pS channel, the
      first mitochondrial channel to be observed by patch-clamp, and by a approximately
      400 pS pore we have recently been able to fully characterize in the inner
      membrane of mitochondria isolated from a colon tumour cell line. This we propose
      to represent a component of the Permeability Transition Pore. The available data
      exclude the previous tentative identification with porin, and indicate that it
      coincides instead with the still molecularly unidentified "maxi" chloride
      channel.

PMID- 19111673
TI  - Characterization of the kinetics and mechanisms of inhibition of drugs
      interacting with the S. cerevisiae multidrug resistance pumps Pdr5p and Snq2p.
AB  - We have developed a novel screening method that measures the kinetics and
      potencies of inhibitors of the yeast multidrug resistance pumps Pdr5p and Snq2p.
      The assay uses the potentiometric fluorescent probe diS-C(3)(3) (as a benchmark
      substrate of both pumps) to distinguish drugs with minimal effects on plasma
      membrane potential as a marker of side-effects on membrane function and
      integrity. Using FK506, its structural analog rapamycin and enniatin B, we showed
      that our assay can also be used to determine the minimum drug concentration
      causing an immediate inhibitory effect and to compare the inhibitory potencies of
      the drug on the two pumps. We found that the protonophore CCCP effectively
      inhibits the transport of diS-C(3)(3) by both pumps and confirmed the activation
      of membrane H(+)-ATPase by CCCP.

PMID- 19111674
TI  - Non-anti-mitotic concentrations of taxol reduce breast cancer cell invasiveness.
AB  - Taxol is widely used in breast cancer chemotherapy. Its effects are primarily
      attributed to its anti-mitotic activity. Microtubule perturbators also exert
      antimetastatic activities which cannot be explained solely by the inhibition of
      proliferation. Voltage-dependent sodium channels (Na(V)) are abnormally expressed
      in the highly metastatic breast cancer cell line MDA-MB-231 and not in MDA-MB-468
      cell line. Inhibiting Na(V) activity with tetrodotoxin is responsible for an
      approximately 0.4-fold reduction of MDA-MB-231 cell invasiveness. In this study,
      we focused on the effect of a single, 2-h application of 10 nM taxol on the two
      cell lines MDA-MB-231 and MDA-MB-468. At this concentration, taxol had no effect
      on proliferation after 7 days and on migration in any cell line. However it led
      to a 40% reduction of transwell invasion of MDA-MB-231 cells. There was no
      additive effect when taxol and tetrodotoxin were simultaneously applied. Na(V)
      activity, as assessed by patch-clamp, indicates that it was changed by taxol pre
      treatment. We conclude that taxol can exert anti-tumoral activities, in cells
      expressing Na(V), at low doses that have no effect on cell proliferation. This
      effect might be due to a modulation of signalling pathways involving sodium
      channels.

PMID- 19111675
TI  - Targeted disruption of the mouse Lipoma Preferred Partner gene.
AB  - LPP (Lipoma Preferred Partner) is a zyxin-related cell adhesion protein that is
      involved in the regulation of cell migration. We generated mice with a targeted
      disruption of the Lpp gene and analysed the importance of Lpp for embryonic
      development and adult functions. Aberrant Mendelian inheritance in heterozygous
      crosses suggested partial embryonic lethality of Lpp(-/-) females. Fertility of
      Lpp(-/-) males was proven to be normal, however, females from Lpp(-/-) x Lpp(-/-)
      crosses produced a strongly reduced number of offspring, probably due to a
      combination of female embryonic lethality and aberrant pregnancies. Apart from
      these developmental and reproductive abnormalities, Lpp(-/-) mice that were born
      reached adulthood without displaying any additional macroscopic defects. On the
      other hand, Lpp(-/-) mouse embryonic fibroblasts exhibited reduced migration
      capacity, reduced viability, and reduced expression of some Lpp interaction
      partners. Finally, we discovered a short nuclear form of Lpp, expressed mainly in
      testis via an alternative promoter.

PMID- 19111677
TI  - Foreword. This issue of Current Problems in Surgery with Drs. Duvvuri and Myers.

PMID- 19111676
TI  - Functions of epidermal growth factor receptor in cisplatin response of thyroid
      cells.
AB  - Epidermal growth factor receptor (EGFR) signal transduction pathway has been
      reported to play a vital role in the biologic progression of several tumours and
      as targets for therapeutic intervention. We have investigated the role of EGFR in
      the thyroid PC Cl3 cells response to the chemo-therapeutic agent cisplatin. It
      was found that cisplatin provoked (1) the activation (phosphorylation) and
      internalization of EGFR, (2) the phosphorylation of mitogen-activated protein
      kinase (MAPK)/p38, (3) the activation of PKC-epsilon, (4) the enhancement of
      matrix metalloproteinase-2 (MMP-2) expression and activity, (5) the generation of
      reactive oxygen species (ROS) and (6) the activation of the apoptotic intrinsic
      pathway. Inhibition or down regulation of EGFR reduced (1) the phosphorylation of
      MAPK/p38, (2) the cisplatin-provoked activation of PKC-epsilon, and (3) the
      activation of caspase-7 and PARP cleavage and the overall cells sensitivity to
      cisplatin. PKC-epsilon inhibition achieved by siRNA blocked MAPK/p38 activation
      and significantly increased the cell resistance to cisplatin. Finally, when the
      cisplatin-induced ROS generation was blocked by using NAD(P)H oxidase inhibitors,
      a decrease in cisplatin-induced MMP-2 enhancement, MAPK/p38 and EGFR activation,
      and caspase-7 proteolysis occurred. In conclusion, these findings supported a
      model in which cisplatin provokes an oxidant-induced MMP-2-dependent EGFR
      transactivation responsible for the induction of cell apoptosis, a process
      ascribable to the intracellular signalling of PKC-epsilon and MAPK/p38.

PMID- 19111678
TI  - Cancer of the head and neck is the sixth most common cancer worldwide.

PMID- 19111679
TI  - Contemporary management of oropharyngeal cancer: anatomy and physiology of the
      oropharynx.

PMID- 19111680
TI  - Electrophysiological evidence of the adaptive task-set inhibition in task
      switching.
AB  - The present study aimed to employ an electrophysiological approach to evaluate
      the adaptive task-set inhibition hypothesis. According to the adaptive task-set
      inhibition hypothesis, task switching should depend on whether the previous trial
      is univalent or bivalent. This study employed a pairwise task-switching paradigm.
      We focused on the second stimulus of a task pair and examined whether its event
      related potential (ERP) can be modulated as a function of the preceding stimulus
      type (i.e., whether the first stimulus of a task pair is univalent or bivalent).
      Although the reaction time (RT) data in this study indicated that the previous
      stimulus type did not affect the subsequent stimulus' performance, we found that
      the Stimulus 2-locked ERP data could be modulated as a function of the Stimulus 1
      type--univalent or bivalent. More importantly, the effect of Task 2 transition
      occurred only when the Stimulus 1 type was bivalent, as seen in the P3b time
      range ERP modulation. Therefore, the current ERP results provide evidence of the
      adaptive task-set inhibition.

PMID- 19111681
TI  - Identification of a novel mutation for phytosterolemia. Genetic analyses of 2
      cases.
AB  - BACKGROUND: Phytosterolemia is one of the genetic disorders causing
      hypercholesterolemia and atherosclerosis together with the accumulation of plant
      sterol in plasma and tissues. The mutations in ABCG5 and ABCG8 genes, encoding
      sterolin-1 and -2, respectively, are responsible for phytosterolemia. METHODS: We
      performed genetic analyses on 2 Japanese phytosterolemia patients. RESULTS: We
      identified 2 mutations in the ABCG5 gene in these patients. The first patient was
      homozygous for a novel mutation, which was a 19-base pair tandem repeat insertion
      in exon 7, leading to a premature termination at codon 288. The second patient
      was a compound heterozygote; one of the mutations was the same as that found in
      the first patient, while the other mutation was a C to T substitution in exon 10,
      resulting in a premature termination at codon 446 (R446X). No other mutation was
      found in the ABCG5 and ABCG8 genes. CONCLUSIONS: This result was concordant with
      previous observations that found most Asian phytosterolemia patients possessed
      mutations in the ABCG5 gene, and the site of the novel mutation was completely
      different from these previous reports, necessitating the extensive analyses for
      phytosterolemia.

PMID- 19111684
TI  - Endoscopic submucosal dissection: established, or still needs improving?

PMID- 19111682
TI  - Rapid diagnostic testing procedures for lysosomal storage disorders: alpha
      glucosidase and beta-galactosidase assays on dried blood spots.
AB  - BACKGROUND: Lysosomal storage disorders (LSDs) are pathologies caused by the
      deficit of lysosomal enzymes; late diagnosis may render therapeutic programs less
      effective. As early, pre-symptomatic detection could change the natural history
      of the disease, we are setting up rapid microassays using dried blood spots (DBS)
      on filter paper. Here we report alpha-glucosidase and beta-galactosidase assays.
      METHODS: Enzymatic activities were evaluated on DBS from five different groups of
      subjects including healthy controls and patients affected with an LSD. A 260-day
      monitoring of DBS preservation at five different temperatures and a comparison of
      the enzymatic activities measured in DBS obtained from a single (sDBS) or a
      double (dDBS) blood drop were performed as well. RESULTS: Both assays could
      clearly distinguish the affected patients from the other subjects analyzed.
      Storage of DBS at 4 degrees C and below allowed a longer preservation of the
      enzymatic activities. No significant differences were detected between sDBS and
      dDBS. CONCLUSIONS: DBS can be used for non-invasive, easy, inexpensive lysosomal
      enzyme assays. Reliability of assays on DBS needs to be checked using a control
      enzyme such as beta-galactosidase. DBS can be still reliably analyzed even if
      generated incidentally by two overlapped drops.

PMID- 19111685
TI  - Diagnosis of elevated-type early gastric cancers by the optimal band imaging
      system.
AB  - BACKGROUND: The endoscopic diagnosis of an elevated-type early gastric cancer is
      often difficult. The optimal band imaging (OBI) system can reconstruct the best
      spectral images decomposed from ordinary endoscopic images with free selection of
      3 wavelengths and provide unmagnified images with high light intensity as well as
      magnified images. OBJECTIVE: To evaluate whether the OBI system facilitates
      detection of the demarcation lines between an elevated-type early gastric cancer
      and surrounding tissue and thus is more helpful for performing endoscopic
      therapy. DESIGN: A prospective study. SETTING: Jichi Medical University, Japan.
      PATIENTS: Seventy-five patients, 81 lesions with an elevated-type early gastric
      cancer. MAIN OUTCOME MEASUREMENTS: A comparison between OBI images and
      conventional endoscopic images in the identification of the demarcation lines of
      an elevated-type early gastric cancer without magnification and the rate of
      success in identifying the abnormal surface structure of cancer by using low
      magnified OBI images. RESULTS: Demarcation lines were easily identified in OBI
      images, even without magnification, because such cancers could be clearly
      distinguished from the surrounding whitish atrophic mucosa. Inexperienced
      endoscopists could determine demarcation lines with significantly greater
      accuracy with unmagnified OBI images than with conventional images. With 40-fold
      magnification, irregular microstructural or nonstructural patterns were also
      found within cancer lesions in all cases studied but in none of the cases in the
      surrounding noncancerous mucosa. CONCLUSIONS: The new contrast images obtained
      with the OBI system enable better determination of the demarcation lines of
      elevated-type early gastric cancers, and this system may be useful for performing
      endoscopic therapy of this type of cancer as a new endoscopic modality.

PMID- 19111687
TI  - Klatskin tumor--palliative therapy: the jury is still out or may be not yet in...
      .

PMID- 19111686
TI  - A new technique for gastric endoscopic submucosal dissection: peroral traction
      assisted endoscopic submucosal dissection.
AB  - BACKGROUND: Compared with conventional EMR, endoscopic submucosal dissection
      (ESD) has a higher en bloc resection rate and complete resection rate, regardless
      of tumor size, in treating gastric neoplasms. However, ESD leads to more
      complications, such as bleeding or perforation, and, in particular, needs more
      procedure time than a conventional EMR. OBJECTIVE: To report a new technique for
      ESD, peroral traction-assisted ESD with suture material, to perform easier and
      more rapid procedures in treating gastric neoplasms and to report the technique's
      early results. DESIGN: A case series. SETTING: A tertiary medical center.
      PATIENTS AND METHODS: A total of 15 patients with gastric adenomas or early
      gastric cancers larger than 10 mm in diameter were consecutively enrolled. After
      marking around the periphery of the lesion, submucosal injection, followed by
      circumferential mucosal incision with a Flex-knife and an insulation-tipped
      knife, was conducted. After that, one hemostatic clip, tied by using a white silk
      suture, was applied at a site of the lesion suitable for oral traction. During
      submucosal dissection, the applied suture material was pulled to the oral side.
      Additional tractions were applied as needed. MAIN OUTCOME MEASUREMENTS: En bloc
      resection rate, procedure time, complications. RESULTS: All lesions were resected
      en bloc with free lateral and vertical margins by using this technique. The mean
      longest lesion size and specimen size were 18.1 mm (range 11-28 mm) and 43.7 mm
      in diameter (range 25-64 mm), respectively. The mean procedure time was 49.6
      minutes (range 28-90 minutes). There was no significant bleeding that required
      blood transfusion or perforation related to the procedures. LIMITATIONS: Single
      endoscopist, small patient number. CONCLUSION: Peroral traction-assisted ESD with
      suture material is useful in treating gastric neoplasms located in various
      regions of the stomach. It may make ESD procedures easier, faster, and safer
      under better direct vision of the submucosal layer.

PMID- 19111688
TI  - Achieving total enteroscopy with capsule endoscopy in all patients: are we
      stretching the limits of technology?

PMID- 19111689
TI  - Small-bowel obstruction: diagnostic comparison between double-balloon endoscopy
      and fluoroscopic enteroclysis, and the outcome of enteroscopic treatment.
AB  - BACKGROUND: Small-bowel obstruction (SBO) sometimes remains undiagnosed and
      untreatable without surgery. OBJECTIVE: To evaluate the diagnostic yields of SBO
      between double-balloon endoscopy (DBE) and fluoroscopic enteroclysis (FE), and
      the outcome of enteroscopic treatment. DESIGN: Single-center, retrospective, and
      prospective study. SETTING: Tertiary-referral hospital. PATIENTS: Between June
      2003 and July 2007, 66 consecutive patients with SBO were enrolled, investigated,
      and treated. MAIN OUTCOME MEASUREMENTS: A comparison of diagnostic yields between
      DBE and FE, and the prognosis after enteroscopic balloon dilation. RESULTS: The
      diagnostic yield of DBE for SBO (95%) was higher than that of FE (71%) in 59
      patients who underwent both examinations (P= .004). The first treatment included
      27 surgical, 25 enteroscopic, and 14 conservative therapies. Of 47 enteroscopic
      balloon dilation procedures in 22 patients, 45 (96%) were successful. Of 16
      patients with Crohn's disease, 11 (69%) remained asymptomatic over the
      postdilation follow-up period but 5 relapsed: 2 recovered by repeated dilations,
      but 3 required surgery. Of 6 patients who had diseases other than Crohn's
      disease, 4 (67%) remained asymptomatic but 2 relapsed: one with remission of
      metastasis recovered by repeated dilations, and one with ischemic enteritis
      required surgery. Anastomotic stricture was an independent marker of the symptom
      free outcome (hazard ratio 0.037-0.084, P= .037). Two acute pancreatitis, one
      perforation, and one exacerbation of SBO complications occurred. LIMITATIONS:
      Small sample size and participation bias. CONCLUSIONS: DBE was useful for the
      diagnosis of SBO. Balloon dilation is considered an alternative to surgery in
      patients with fibrotic strictures both related and unrelated to Crohn's disease.

PMID- 19111691
TI  - Natural orifice transluminal endoscopic surgery: breaching the boundaries safely.

PMID- 19111690
TI  - Transgastric ventral hernia repair: a controlled study in a live porcine model
      (with videos).
AB  - BACKGROUND: Ventral hernia repair is currently performed via open surgery or
      laparoscopic approach. OBJECTIVE: To develop an alternative ventral hernia repair
      technique. SETTING: Acute and survival experiments on twelve 50-kg pigs. DESIGN
      AND INTERVENTIONS: An endoscope was introduced transgastrically into the
      peritoneal cavity. An abdominal wall hernia was created through a 5-mm skin
      incision followed by a 5-cm-long incision of the abdominal wall muscles and
      aponeurosis. A hernia repair technique was developed in 3 acute experiments. Then
      animals were randomized into 2 groups. In the experimental group (5 animals) Gore
      Tex mesh was transgastrically attached to the abdominal wall, repairing the
      previously created abdominal wall hernia. In the control group (4 animals), the
      hernia was not repaired. In both groups, the endoscope was then withdrawn into
      the stomach, and the gastric wall incision was closed with T-bars. The animals
      survived for 2 weeks and were then euthanized. MAIN OUTCOME MEASUREMENT: The
      presence of ventral hernia on necropsy. RESULTS: In the control group, the
      ventral hernia was present on necropsy in all animals. In the experimental group,
      the ventral hernia was easily repaired, with no evidence of hernia on necropsy.
      In the first animal in the experimental group, necropsy revealed infected mesh.
      After this discovery, we used sterilized cover for mesh delivery and did not find
      any signs of infection in 4 subsequent study animals. LIMITATION: The study was
      performed in a porcine model. CONCLUSIONS: Transgastric ventral hernia repair is
      feasible, technically easy, and effective. It can become a less invasive
      alternative to the currently used laparoscopic and surgical ventral hernia
      repair.

PMID- 19111692
TI  - The pregnant fellow--scoping for two.

PMID- 19111693
TI  - Systematic review of narrow-band imaging for the detection and differentiation of
      neoplastic and nonneoplastic lesions in the colon (with videos).

PMID- 19111694
TI  - Pinch force and forearm-muscle load during routine colonoscopy: a pilot study.
AB  - BACKGROUND AND OBJECTIVE: Overuse injuries of the hand, wrist, forearm, and
      shoulder are common among endoscopists and may be from repetitive pinching and
      gripping forces or awkward posturing. In this pilot study, we evaluated distal
      upper-extremity musculoskeletal load during colonoscopy (1) to confirm the
      feasibility of performing ergonomic measurements in endoscopists and (2) to
      identify tasks that may contribute to overuse injuries. DESIGN AND SUBJECTS:
      Three experienced gastroenterologists were evaluated during 3 colonoscopies each.
      SETTING: Veterans Affairs Medical Center, San Francisco, California. MAIN OUTCOME
      MEASUREMENT: Right-thumb pinch force using a thumb-force sensor and bilateral
      forearm-muscle activity using electromyography. RESULTS: The mean duration of the
      9 colonoscopies was 19.5 minutes. The highest mean (SD) right-thumb peak pinch
      forces occurred during left (10.4 [4.1] N) and right (10.1 [4.5] N) colon
      insertion, which exceeded the injury threshold of 10 N. Mean peak forearm-muscle
      activity was also greatest during left and right colon insertion. Activity of the
      left abductor pollicis longus, left extensor carpi radialis, and right extensor
      carpi radialis exceeded the American Conference of Industrial Hygienists (ACGIH)
      hand activity level (HAL) action limit. The left extensor carpi radialis was at
      the ACGIH HAL threshold limit. LIMITATIONS: The small sample size, no force
      measurement for the left thumb, and all the gastroenterologists were men.
      CONCLUSION: The pinch forces and forearm-muscle loads applied during routine
      colonoscopy may pose a risk for overuse injuries at the elbow and wrist.

PMID- 19111695
TI  - En bloc esophageal mucosectomy for concentric circumferential mucosal resection
      (with video).
AB  - BACKGROUND: With conventional EMR, specimens are fragmented, metaplasia may be
      left behind, and invasive lesions could be missed because of incomplete sampling.
      Concentric subtotal esophageal mucosectomy would address these limitations.
      OBJECTIVE: To examine en bloc esophageal mucosectomy (EEM). DESIGN: A prospective
      case series. SETTING: An academic hospital. SUBJECTS: Nine swine. INTERVENTIONS:
      Conventional EMR was performed in the proximal esophagus. The submucosal space
      was entered, and the distal two thirds of the esophageal mucosa was freed with
      blunt dissection. A snare was threaded over the column of mucosa to the
      gastroesophageal junction. The column was resected, and the mucosa was retrieved.
      MAIN OUTCOME AND MEASUREMENTS: Clinical examination, follow-up endoscopy,
      necropsy, and gross and histopathologic examination. RESULTS: EEM permitted
      subtotal esophageal mucosectomy in 9 of 9 swine (tissue specimens removed ranged
      9-15 cm in length). The mean procedure duration was 110 minutes. In the survival
      series, 4 of 4 swine thrived after surgery, for 9 to 13 days. At 9 days, there
      was no evidence of a perforation, stricture, or leak. At 13 days, 2 swine had a
      mild proximal stricture, which was easily traversed with a 9.8-mm gastroscope. On
      necropsy, the mediastinal and thoracic cavities were unremarkable in 3 of 4
      swine. One swine was found to have a contained abscess containing cellulose,
      presumably secondary to ingestion of wood-chip bedding material postoperatively.
      Reepithelialization was present on histologic examination. LIMITATIONS: An animal
      study. CONCLUSIONS: EEM is feasible and enabled concentric subtotal esophageal
      mucosal resection. The technique could completely and circumferentially excise
      intramucosal lesions. Longer follow-up and larger studies are needed to evaluate
      infection, stricture, and safety.

PMID- 19111696
TI  - Gastric arteriovenous malformation: a rare cause of upper GI bleed.

PMID- 19111697
TI  - Magnifying endoscopic observation of primary follicular lymphoma of the duodenum
      by using the narrow-band imaging system.

PMID- 19111698
TI  - Repair of an endoscopic submucosal dissection-induced rectal perforation with
      band ligation.

PMID- 19111699
TI  - Osteoclastic and pleomorphic giant cell tumors of the pancreas diagnosed via EUS
      guided FNA: unique clinical, endoscopic, and pathologic findings in a series of 5
      patients.
AB  - INTRODUCTION: Osteoclastic and pleomorphic giant cell tumors of the pancreas are
      rare entities that have been typically described only in single case reports. We
      report on our experience with a series of 5 patients with pancreatic giant cell
      tumors seen at our institution. METHODS: This was a retrospective study involving
      a search of the study institution's medical records from 2001 to 2007 for
      patients diagnosed with giant cell-containing neoplasms of the pancreas. RESULTS:
      Five patients (2 women, 3 men) were identified. Age range was 59 to 81 years,
      with a mean of 70.2 years. None were current or former smokers. None had a
      history of alcohol abuse or preexisting pancreatitis of any kind. On EUS, tumors
      tended to be large, with a mean diameter of 47 mm (range 20-70 mm). All tumors
      had a heterogeneous echotexture and a distinct appearance when compared with the
      typical appearance of adenocarcinoma when viewed via EUS. The diagnosis of giant
      cell tumor of the pancreas, as well as the subtype, was made via EUS-guided FNA
      of the pancreatic lesion. Patients with pleomorphic giant cell tumors of the
      pancreas had a poor clinical course with a rapid decline, whereas those with
      mixed or osteoclastic giant cell tumors tended to have a better outcome, with a
      greater long-term survival. One patient is still alive more than 18 months after
      diagnosis. LIMITATION: Retrospective study. CONCLUSIONS: Giant cell tumors of the
      pancreas have unique clinical, endoscopic, and cytologic features. The risk
      factors for these lesions may be different from those associated with pancreatic
      adenocarcinoma. Some giant cell tumor subtypes may carry a more favorable
      prognosis than pancreatic adenocarcinoma, and awareness and recognition of these
      differences can affect patient care.

PMID- 19111700
TI  - Endoscopic fenestration of duodenal stents using argon plasma to facilitate ERCP.
AB  - BACKGROUND: The presence of a duodenal stent may hinder attempts at ERCP for
      treatment of malignant biliary obstruction. OBJECTIVE: We describe 2 patients in
      whom endoscopic fenestration of indwelling duodenal stents with an argon plasma
      coagulator facilitated successful ERCP. DESIGN: Single-center retrospective case
      series. SETTING: Tertiary-referral center. PATIENTS: Both patients had
      unresectable biliary malignancy with both duodenal and biliary obstruction.
      INTERVENTION AND RESULTS: Windows were cut into indwelling duodenal stents with
      argon plasma, which exposed the underlying papilla and allowed successful ERCP
      and stent placement. LIMITATIONS: Retrospective study and the small sample size.
      CONCLUSIONS: Fenestration of duodenal stents using argon plasma is a simple
      technique that can facilitate ERCP.

PMID- 19111701
TI  - Management of antiplatelets in elective GI endoscopies: a collaboration between
      the endoscopist and the cardiologist.

PMID- 19111703
TI  - Infection control during endoscopy: a constant threat with large pools of
      patients with unknown status.

PMID- 19111705
TI  - Endoscopic and EUS features of gastric inflammatory fibroid polyps.

PMID- 19111707
TI  - Narrow-band imaging in addition to a transparent hood for much more polyp
      detection.

PMID- 19111708
TI  - Malfunctioning covered biliary metallic stents: ineffective trimming or effective
      removal?

PMID- 19111710
TI  - Polypectomy leading to the resolution of a liver abscess.

PMID- 19111711
TI  - The left pinkie maneuver of the colonoscopy.

PMID- 19111713
TI  - On colonoscopy without sedation.

PMID- 19111714
TI  - Computerized planning of prostate cryosurgery using variable cryoprobe insertion
      depth.
AB  - The current study presents a computerized planning scheme for prostate
      cryosurgery using a variable insertion depth strategy. This study is a part of an
      ongoing effort to develop computerized tools for cryosurgery. Based on typical
      clinical practices, previous automated planning schemes have required that all
      cryoprobes be aligned at a single insertion depth. The current study investigates
      the benefit of removing this constraint, in comparison with results based on
      uniform insertion depth planning as well as the so-called "pullback procedure".
      Planning is based on the so-called "bubble-packing method", and its quality is
      evaluated with bioheat transfer simulations. This study is based on five 3D
      prostate models, reconstructed from ultrasound imaging, and cryoprobe active
      length in the range of 15-35 mm. The variable insertion depth technique is found
      to consistently provide superior results when compared to the other placement
      methods. Furthermore, it is shown that both the optimal active length and the
      optimal number of cryoprobes vary among prostate models, based on the size and
      shape of the target region. Due to its low computational cost, the new scheme can
      be used to determine the optimal cryoprobe layout for a given prostate model in
      real time.

PMID- 19111715
TI  - Storage stability of freeze-dried Lactobacillus acidophilus (La-5) in relation to
      water activity and presence of oxygen and ascorbate.
AB  - Storage stability of freeze-dried Lactobacillus acidophilus was found to depend
      on water activity (0.11-0.43), oxygen level (atmospheric oxygen level and <4%
      oxygen compared) and presence of sodium ascorbate (0% and 10% (w/w)). Increasing
      water activities decreased bacterial survival, and a reduced oxygen level (<4%
      oxygen) improved the storage stability, which strongly indicates a connection
      between oxidative reactions and bacterial instability. The detrimental effect of
      atmospheric oxygen was reduced by including ascorbate in the freeze drying
      medium. However, when ascorbate was present a pink/red colour was observed on the
      surface of the dried samples increasing with the water activity and oxygen level.
      Increased water activity lead to increased browning also for samples without
      ascorbate. Free radicals were detected in the dried bacteria by ESR spectroscopy
      (broad single-peak ESR spectra), where the shape and the g-value was found to
      depend on the presence of ascorbate and the extent of browning. For increasing
      water activities the content of radicals increased to a certain level, after
      which it levelled off and/or decreased. The highest concentrations of radicals
      were detected in the dried bacteria with highest survival for a given water
      activity, i.e. low oxygen level and presence of ascorbate, pointing towards a
      role of semi-stable ascorbyl radicals as a "dead end" for otherwise detrimental
      free radical reactions.

PMID- 19111717
TI  - Obstetric fistulae in West Africa: patient perspectives.
AB  - OBJECTIVE: The objective of this study is to gain insight into the nature of
      obstetric fistulae in Africa through patient perspectives. STUDY DESIGN: At
      l'Hopital Saint Jean de Dieu in Tanguieta, Benin, 37 fistula patients underwent
      structured interviews about fistula cause, obstacles to medical care, prevention,
      and reintegration by 2 physicians via interpreters. RESULTS: The majority of
      participants (43%) thought their fistulae were a result of trauma from the
      operative delivery. Lack of financial resources (49%) was the most commonly
      reported obstacle to care, and prenatal care (38%) was most frequently reported
      as an intervention that may prevent obstetric fistulae. The majority (49%) of the
      participants requested no further reintegration assistance aside from surgery.
      CONCLUSION: Accessible emergency obstetric care is necessary to decrease the
      burden of obstetric fistulae in Africa. This may be accomplished through
      increased and improved health care facilities and education of providers and
      patients.

PMID- 19111716
TI  - Attenuation of amphetamine-induced activity by the non-selective muscarinic
      receptor agonist, xanomeline, is absent in muscarinic M4 receptor knockout mice
      and attenuated in muscarinic M1 receptor knockout mice.
AB  - The muscarinic acetylcholine receptor (mAChR) agonist, xanomeline, attenuates
      amphetamine-induced activity in WT mice. This effect is abolished in mice lacking
      the M(4) muscarinic acetylcholine receptor (M(4) mAChR KO) and partially
      attenuated in mice lacking M(1) muscarinic acetylcholine receptor (M(1) mAChR
      KO). Collectively, these data suggest that the efficacy exhibited by xanomeline
      in the mouse amphetamine-induced hyperactivity model, is mediated predominantly
      by M(4) muscarinic acetylcholine receptors, and that M(1) muscarinic
      acetylcholine receptors may play a more minor role. This supports the hypothesis
      that activation of M(4), and to a lesser extent M(1) muscarinic acetylcholine
      receptors, may represent a potential target for the treatment of psychosis seen
      in schizophrenia.

PMID- 19111718
TI  - An evaluation of knot integrity when tied robotically and conventionally.
AB  - OBJECTIVE: The purpose of this study was to evaluate the knot integrity of 3
      commonly used sutures in sacrocolpopexy that were tied conventionally (by hand)
      and robotically. STUDY DESIGN: Knots were tied with polyglactin 910,
      polypropylene, and polyester, with 5-6 knots tied, depending on the suture used.
      We compared the knots that were subjected to tensile force until the suture broke
      or untied. RESULTS: The mean force that was required for the suture to untie was
      47.7 +/- 18.8 (SD) Newtons and was seen only among the robotically tied
      polyglactin 910 knots. Robotically tied polyglactin 910 knots were significantly
      weaker than all other robotic and conventional knots that were tested (P < .05).
      The tying modality and material interaction was significant (P < .001), which
      suggests that the effect of suture material varied, depending on the tying
      modality. CONCLUSION: Knot failure rates for conventional or robotically tied
      suture varied based on the suture material that was used.

PMID- 19111719
TI  - Investigating the risk of hypertension shortly after pregnancies complicated by
      preeclampsia.
AB  - OBJECTIVE: Women with a history of preeclampsia are at increased risk for long
      term cardiovascular morbidity and mortality. This study assessed whether a
      pregnancy complicated by preeclampsia is associated with an increased prevalence
      of maternal hypertension and other cardiovascular risk factors shortly after
      delivery. STUDY DESIGN: Seventy-nine cases and 140 controls that had been
      enrolled in a prospective case-control study were evaluated in this planned
      follow-up analysis. The presence of hypertension, diabetes and dyslipidemia were
      assessed by standardized questionnaire 6-13 months after delivery. RESULTS: Women
      with preeclampsia were significantly more likely than controls to have
      hypertension (adjusted odds ratio, 13.92; 95% CI, 5.17-37.4; P < .001) after
      adjusting for confounders. Women with preterm preeclampsia also had an increased
      odds of hypertension (adjusted odds ratio, 18.31; 95% CI, 5.04-66.46; P < .001)
      compared with controls. CONCLUSION: Pregnancy complications, such as
      preeclampsia, may provide opportunities to identify women at risk for
      cardiovascular morbidity years before the onset of disease, allowing a window for
      prevention and intervention.

PMID- 19111720
TI  - Focal adhesion kinase signaling pathway participates in the formation of
      choroidal neovascularization and regulates the proliferation and migration of
      choroidal microvascular endothelial cells by acting through HIF-1 and VEGF
      expression in RPE cells.
AB  - Choroidal neovascularization (CNV) is one of the most frequent causes of severe
      and progressive vision loss, while its pathogenesis is still poorly understood.
      Focal adhesion kinase (FAK), a non-receptor tyrosine kinase, plays a crucial role
      in linking signals initiated by both the extracellular matrix (ECM) and soluble
      signaling factors and controls essential cellular processes. Extensive evidence
      has shown that FAK is activated in angiogenic response. This study aims to
      investigate the effect of FAK on CNV formation. The Brown-Norway (BN) rats
      underwent laser rupture of Bruch's membrane to induce CNV and were then killed at
      1, 3, 7, and 14 days following laser injury. Immunofluorescence and Western blot
      were processed to detect FAK protein. Retinal pigment epithelial (RPE) cells were
      cultured under hypoxia and RNA interference (RNAi) technique was used to knock
      down the FAK gene in RPE cells. Expression of hypoxia inducible factor-1 (HIF
      1alpha) and vascular endothelial growth factor (VEGF) in RPE cells were
      investigated by RT-PCR and Western blot. Two kinds of coculture models were used
      to observe the effects of specific blockade of FAK in RPE cells on the
      proliferation and migration of choroidal microvascular endothelial cells (CECs),
      respectively. FAK was highly expressed in the rat RPE-choroid tissue after
      photocoagulation. In vitro experiment showed that FAK was involved in hypoxia
      signaling in cultured RPE cells. The absence of FAK effectively reduced the
      expression of hypoxia-induced HIF-1alpha and VEGF in RPE cells, resulting in the
      inhibition of proliferation and migration of CECs. Our results suggest that FAK
      pathway activation plays a role in the development of CNV, and regulates the
      proliferation and migration of CECs by acting through HIF-1 and then up
      regulating the expression of the angiogenic factor VEGF in RPE cells. It is
      reasonable to propose that FAK siRNA will potentially provides a means to
      attenuate the strong stimuli for neovascularization in CNV-dependent disorders,
      which could present a therapeutically relevant strategy for the inhibition of
      CNV.

PMID- 19111722
TI  - Echinococcus granulosus: protoscolicidal effect of high intensity focused
      ultrasound.
AB  - High intensity focused ultrasound (HIFU) is a new non-invasive technique which
      can cause cell death and tissue necrosis by focusing high-energy ultrasonic waves
      on a single location. The aim of our work is to investigate the damaging effect
      of HIFU on Echinococcus granulosus protoscolices, as well as its inhibitory
      effect on growth of hydatid cysts derived from protoscolices. The damaging effect
      of HIFU on protoscolices was investigated by following parasite mortality after
      irradiation, while the inhibitory effect was investigated by infection
      experiments in vivo. The results demonstrated that HIFU was able to damage
      protoscolices and the protoscolicidal effect was dose-dependent and showed late
      onset. The growth of protoscolices that survived the exposure to HIFU was
      obviously suppressed in vitro, and the mean weight of hydatid cysts resulting
      from such protoscolices in the experimental group was less than that in controls.
      Evidences including the protoscolicidal effect, fragmentized protoscolices and
      low post exposure temperatures, suggest that cavitation may contribute to the
      protoscolicidal effect of HIFU. In addition, the structure of the germinal
      membrane in cysts developing from the irradiated protoscolices was not as normal
      or intact as that from non-irradiated ones, and morphological changes related to
      degeneration were observed, suggesting that HIFU could prevent protoscolices from
      developing normal germinal membrane and consequently stop the proliferation of
      secondary hydatid cysts. HIFU demonstrated damaging effect on protoscolices,
      inhibited the growth of protoscolices in vitro and in vivo, and could be a
      possible therapeutic option for cystic echinococcosis.

PMID- 19111721
TI  - Pharmacological evidence for a role of peroxynitrite in the pathophysiology of
      spinal cord injury.
AB  - Evidence suggests that the reactive oxygen species peroxynitrite (PN) is an
      important player in the pathophysiology of acute spinal cord injury (SCI). In the
      present study, we examined the ability of tempol, a catalytic scavenger of PN
      derived free radicals, to alleviate oxidative damage, mitochondrial dysfunction
      and cytoskeletal degradation following a severe contusion (200 kdyn force) SCI in
      female Sprague-Dawley rats. PN-mediated oxidative damage in spinal cord tissue,
      including protein nitration, protein oxidation and lipid peroxidation was
      significantly reduced by acute tempol treatment (300 mg/kg, i.p. within 5 min
      post-injury). Injury-induced mitochondrial respiratory dysfunction, measured
      after 24 h in isolated mitochondria, was partially reversed by tempol along with
      an attenuation of oxidative damage to mitochondrial proteins. Mitochondrial
      dysfunction disrupts intracellular Ca(2+) homeostasis contributing to calpain
      mediated axonal cytoskeletal protein (alpha-spectrin, 280 kD) degradation.
      Increased levels of alpha-spectrin breakdown proteins (SBDP 145 kD and 150 kD)
      were significantly decreased at 24 h in tempol-treated rats indicative of spinal
      axonal protection. However, a therapeutic window analysis showed that the axonal
      cytoskeletal protective effects require tempol dosing within the first hour after
      injury. Nevertheless, these findings are the first to support the concept that PN
      is an important neuroprotective target in early secondary SCI, and that there is
      a mechanistic link between PN-mediated oxidative compromise of spinal cord
      mitochondrial function, loss of intracellular Ca(2+) homeostasis and calpain
      mediated proteolytic axonal damage.

PMID- 19111723
TI  - Electronic clinical challenges and images in GI. Image 3.

PMID- 19111724
TI  - Clinical challenges and images in GI. Image 2: schistosomiasis.

PMID- 19111725
TI  - Zinc replenishment reverses overexpression of the proinflammatory mediator S100A8
      and esophageal preneoplasia in the rat.
AB  - BACKGROUND & AIMS: Zinc deficiency is implicated in the pathogenesis of human
      esophageal cancer. In the rat esophagus, it induces cell proliferation, modulates
      genetic expression, and enhances carcinogenesis. Zinc-replenishment reverses
      proliferation and inhibits carcinogenesis. The zinc-deficient rat model allows
      the identification of biological differences affected by zinc during early
      esophageal carcinogenesis. METHODS: We evaluated gene expression profiles of
      esophageal epithelia from zinc-deficient and replenished rats vs zinc-sufficient
      rats using microarray analysis. We characterized the role of the top-up-regulated
      gene S100A8 in esophageal hyperplasia/reversal and in chemically induced
      esophageal carcinogenesis in zinc-modulated animals by immunohistochemistry and
      real-time quantitative polymerase chain reaction. RESULTS: The hyperplastic
      deficient esophagus has a distinct expression signature with the proinflammation
      genes S100 calcium binding protein A8 (S100A8) and A9 (S100A9) up-regulated 57
      fold and 5-fold, respectively. Zinc replenishment rapidly restored to control
      levels the expression of S100A8/A9 and 27 other genes and reversed the
      hyperplastic phenotype. With its receptor for advanced glycation end products
      (RAGE), colocalization and overexpression of S100A8 protein occurred in the
      deficient esophagus that overexpressed nuclear factor kappaBeta p65 and
      cyclooxygenase-2 (COX-2) protein. Zinc replenishment, but not a COX-2 inhibitor,
      reduced the overexpression of these 4 proteins. Additionally, esophageal
      S100A8/A9 messenger RNA levels were associated directly with the diverse
      tumorigenic outcome in zinc-deficient and zinc-replenished rats. CONCLUSIONS: In
      vivo zinc regulates S100A8 expression and modulates the link between S100A8-RAGE
      interaction and downstream nuclear factor kappaBeta/COX-2 signaling. The finding
      that zinc regulates an inflammatory pathway in esophageal carcinogenesis may lead
      to prevention and therapy for this cancer.

PMID- 19111726
TI  - Alcohol types and sociodemographic characteristics as risk factors for Barrett's
      esophagus.
AB  - BACKGROUND & AIMS: Little is known about the effects of alcohol use and
      sociodemographics on the risk of Barrett's esophagus, a precursor to esophageal
      adenocarcinoma. We evaluated the association between alcohol use, alcohol type,
      sociodemographic profiles, other lifestyle factors, and the risk of Barrett's
      esophagus. METHODS: With the use of a case-control study within the Kaiser
      Permanente Northern California membership, patients with a new diagnosis of
      Barrett's esophagus (n = 320) diagnosed between 2002 and 2005 were matched to
      persons with gastroesophageal reflux disease (GERD; n = 316) and to population
      controls (n = 317). We collected information using validated questionnaires
      during direct in-person interviews. Analyses used multivariate unconditional
      logistic regression. RESULTS: Total alcohol use was not significantly associated
      with the risk of Barrett's esophagus, although stratification by beverage type
      showed an inverse association for wine drinkers compared with nondrinkers (>/=7
      drinks of wine per week vs none: odds ratio, 0.44; 95% confidence interval, 0.20
      0.99; multivariate analysis). Among population controls, those who preferred wine
      were more likely to have college degrees and regularly take vitamin supplements
      than those who preferred beer or liquor, although adjustment for these factors or
      GERD symptoms did not eliminate the inverse association between wine consumption
      and Barrett's esophagus. Education status was significantly inversely associated
      with the risk of Barrett's esophagus. CONCLUSIONS: There are associations between
      alcohol types, socioeconomic status, and the risk of Barrett's esophagus.
      Although choice of alcoholic beverages was associated with several factors,
      multiple adjustments (including for GERD) did not eliminate the association
      between alcohol and Barrett's esophagus. Further research to evaluate the
      associations among socioeconomic status, GERD, and Barrett's esophagus is
      warranted.

PMID- 19111728
TI  - Is inflammatory bowel disease a vascular disease? Targeting angiogenesis improves
      chronic inflammation in inflammatory bowel disease.

PMID- 19111727
TI  - Endothelial caveolin-1 regulates pathologic angiogenesis in a mouse model of
      colitis.
AB  - BACKGROUND & AIMS: Increased vascular density has been associated with
      progression of human inflammatory bowel diseases (IBDs) and animal models of
      colitis. Pathologic angiogenesis in chronically inflamed tissues is mediated by
      several factors that are regulated at specialized lipid rafts known as caveolae.
      Caveolin-1 (Cav-1), the major structural protein of caveolae in endothelial
      cells, is involved in the regulation of angiogenesis, so we investigated its role
      in experimental colitis. METHODS: Colitis was induced by administration of
      dextran sodium sulfate to wild-type and Cav-1(-/-) mice, as well as Cav-1(-/-)
      mice that overexpress Cav-1 only in the endothelium. Colon tissues were analyzed
      by histologic analyses. Leukocyte recruitment was analyzed by intravital
      microscopy; angiogenesis was evaluated by immunohistochemistry and in vivo disk
      assays. RESULTS: Cav-1 protein levels increased after the induction of colitis in
      wild-type mice. In Cav-1(-/-) mice or mice given a Cav-1 inhibitory peptide, the
      colitis histopathology scores, vascular densities, and levels of inflammatory
      infiltrates decreased significantly compared with controls. Lower levels of
      leukocyte and platelet rolling and adhesion colitis also were observed in Cav-1(
      /-) mice and mice given a Cav-1 inhibitory peptide, compared with controls. Cav
      1(-/-) mice that received transplants of wild-type bone marrow had a lower
      colitis score than wild-type mice. Data from mice that overexpress Cav-1 only in
      the endothelium indicated that endothelial Cav-1 is the critical regulator of
      colitis. Genetic deletion or pharmacologic inhibition of endothelial Cav-1 also
      significantly decreased vascular densities and angiogenesis scores, compared with
      controls. CONCLUSIONS: Endothelial Cav-1 mediates angiogenesis in experimental
      colitis. Modulation of Cav-1 could provide a novel therapeutic target for IBD.

PMID- 19111737
TI  - Treatment outcomes in interstitial cystitis.

PMID- 19111738
TI  - Re: Takmaz SA, et al. Analgesic effect of 8- and 16-mg lornoxicam administered
      before shock wave lithotripsy: a randomized, double-blind, controlled study
      (Urology 2008;72:282-285).

PMID- 19111739
TI  - Re: Cho KS, et al. Grade of hydronephrosis and tumor diameter as preoperative
      prognostic factors in ureteral transitional cell carcinoma (Urology 2007;70:662
      666).

PMID- 19111741
TI  - Re: John H, Blick N: Mid-term outcome after bulbourethral composite suspension
      for postprostatectomy incontinence. (Urology 2008;71:1191-1195).

PMID- 19111743
TI  - Role of polymorphisms of interleukin-1 receptor antagonist gene in systemic
      oncogenesis: significant etiopathologic connections besides in benign prostatic
      hyperplasia.

PMID- 19111744
TI  - Re: Keqin z, et al. Clinical significance of intravesical prostatic protrusion in
      patients with benign prostatic enlargement (Urology 2007;70:1096-1099).

PMID- 19111745
TI  - Membrane remodeling and glucose in Drosophila melanogaster: a test of rapid cold
      hardening and chilling tolerance hypotheses.
AB  - Insect cold tolerance varies at both the population and species levels.
      Carbohydrate cryoprotectants and membrane remodeling are two main mechanisms
      hypothesised to increase chilling tolerance in Drosophila melanogaster, as part
      of both long-term (i.e., evolutionary) change and rapid cold-hardening (RCH). We
      used cold-selected lines of D. melanogaster with and without a pre-exposure that
      induces RCH to test three hypotheses: (1) that increased cold tolerance would be
      associated with increased free glucose; (2) that increased cold tolerance would
      be associated with desaturation of membrane phospholipid fatty acids; and (3)
      that increased cold tolerance would be associated with a change in phospholipid
      head group composition. We used colourimetric assays to measure free glucose and
      a combination of thin layer chromatography-flame ionization detection and gas
      chromatography to measure membrane composition. We observed a consistent decrease
      in free glucose with RCH, and no relationship between free glucose and basal cold
      tolerance. Also, phospholipid head group ratios and fatty acid composition showed
      no change following an RCH treatment. Thus, we conclude that changes in free
      glucose and membrane composition are unlikely to be significant determinants of
      variation in cold tolerance of D. melanogaster.

PMID- 19111746
TI  - Hydrolyzable tannins as "quantitative defenses": limited impact against Lymantria
      dispar caterpillars on hybrid poplar.
AB  - The high levels of tannins in many tree leaves are believed to cause decreased
      insect performance, but few controlled studies have been done. This study tested
      the hypothesis that higher foliar tannin levels produce higher concentrations of
      semiquinone radicals (from tannin oxidation) in caterpillar midguts, and that
      elevated levels of radicals are associated with increased oxidative stress in
      midgut tissues and decreased larval performance. The tannin-free leaves of hybrid
      poplar (Populus tremulaxP. alba) were treated with hydrolyzable tannins,
      producing concentrations of 0%, 7.5% or 15% dry weight, and fed to Lymantria
      dispar caterpillars. As expected, larvae that ingested control leaves contained
      no measurable semiquinone radicals in the midgut, those that ingested 7.5%
      hydrolyzable tannin contained low levels of semiquinone radicals, and those that
      ingested 15% tannin contained greatly increased levels of semiquinone radicals.
      Ingested hydrolyzable tannins were also partially hydrolyzed in the midgut.
      However, increased levels of semiquinone radicals in the midgut were not
      associated with oxidative stress in midgut tissues. Instead, it appears that
      tannin consumption was associated with increased metabolic costs, as measured by
      the decreased efficiency of conversion of digested matter to body mass (ECD).
      Decreased ECD, in turn, decreased the overall efficiency of conversion of
      ingested matter to body mass (ECI). Contrary to our hypothesis, L. dispar larvae
      were able to maintain similar growth rates across all tannin treatment levels, in
      part, because of compensatory feeding. We conclude that hydrolyzable tannins act
      as "quantitative defenses" in the sense that high levels appear to be necessary
      to increase levels of semiquinone radicals in the midguts of caterpillars.
      However, these putative resistance factors are not sufficient to decrease the
      performance of tannin-tolerant caterpillars such as L. dispar.

PMID- 19111747
TI  - DFT conformation and energies of amylose fragments at atomic resolution. Part 1:
      Syn forms of alpha-maltotetraose.
AB  - DFT optimization studies of 90 syn alpha-maltotetraose (DP-4) amylose fragments
      have been carried out at the B3LYP/6-311++G** level of theory. The DP-4 fragments
      studied include V-helix, tightly bent conformations, a boat, and a (1)C(4)
      conformer. The standard hydroxymethyl rotamers (gg, gt, tg) were examined at
      different locations in the residue sequence, and their influence on the bridge
      conformations phi/psi values and conformer energy is described. Hydroxyl groups
      were considered to be homodromic, that is, they are either in the all clockwise,
      'c', or all counterclockwise, 'r'. Energy differences between conformations are
      examined in order to assess the stability of the different conformations and to
      identify the sources of energy that dictate amylose polymer formation. A small
      nearly cyclic compact structure is of low energy as one would expect when these
      flexible molecules are studied in vacuo. Many conformations in which the only
      differences are a single hydroxymethyl variation in the residue sequence show
      similar energies and bridge conformations, with trends being a result of the
      hydroxymethyl as well as hydroxyl orientation. In general the 'c' structures are
      of lower energy than the 'r' structures, although this is only true for the in
      vacuo state. The solvent dependence on conformational preference of several low
      energy DP-4 structures was investigated via the continuum solvation method COSMO.
      These results suggest that the 'r' structures may be favored for fully solvated
      molecules.

PMID- 19111748
TI  - DFT conformation and energies of amylose fragments at atomic resolution. Part 2:
      'Band-flip' and 'kink' forms of alpha-maltotetraose.
AB  - In Part 2 of this series of DFT optimization studies of alpha-maltotetraose, we
      present results at the B3LYP/6-311++G** level of theory for conformations denoted
      'band-flips' and 'kinks'. Recent experimental X-ray studies have found examples
      of amylose fragments with conformations distorted from the usual syn forms, and
      it was of interest to examine these novel structural motifs by the same high
      level DFT methods used in Part 1. As in Part 1, we have examined numerous
      hydroxymethyl rotamers (gg, gt, and tg) at different locations in the residue
      sequence, and include the two hydroxyl rotamers, the clockwise 'c' and
      counterclockwise 'r' forms. A total of fifty conformations were calculated and
      energy differences were found to attempt to identify those sources of electronic
      energy that dictate stressed amylose conformations. Most stressed conformations
      were found to have relative energies considerably greater (i.e., approximately 4
      to 12 kcal/mol) than the lowest energy syn forms. Relative energy differences
      between 'c' and 'r' forms are somewhat mixed with some stressed conformations
      being 'c' favored and some 'r' favored, with the lowest energy 'kink' form being
      an all-gg-r conformation with the 'kink' in the bc glycosidic dihedral angles.
      Comparison of our calculated structures with experimental results shows very
      close correspondence in dihedral angles.

PMID- 19111749
TI  - Crystal structure of rhizavidin: insights into the enigmatic high-affinity
      interaction of an innate biotin-binding protein dimer.
AB  - Rhizavidin, from the proteobacterium Rhizobium etli, exhibits high affinity
      towards biotin but maintains an inherent dimeric quaternary structure and thus,
      differs from all other known tetrameric avidins. Rhizavidin also differs from the
      other avidins, since it lacks the characteristic tryptophan residue positioned in
      the L7,8 loop that plays a crucial role in high-affinity binding and oligomeric
      stability of the tetrameric avidins. The question is, therefore, how does the
      dimer exist and how is the high biotin-binding affinity retained? For this
      purpose, the crystal structures of apo- and biotin-complexed rhizavidin were
      determined. The structures reveal that the rhizavidin monomer exhibits a topology
      similar to those of other members of the avidin family, that is, eight
      antiparallel beta-strands that form the conventional avidin beta-barrel. The
      quaternary structure comprises the sandwich-like dimer, in which the extensive 1
      4 intermonomer interface is intact, but the 1-2 and 1-3 interfaces are
      nonexistent. Consequently, the biotin-binding site is partially accessible, due
      to the lack of the tryptophan "lid" that distinguishes the tetrameric structures.
      In rhizavidin, a disulfide bridge connecting the L3,4 and L5,6 loops restrains
      the L3,4 loop conformation, leaving the binding-site residues essentially
      unchanged upon biotin binding. Our study suggests that in addition to the
      characteristic hydrogen bonding and hydrophobic interactions, the preformed
      architecture of the binding site and consequent shape complementarity play a
      decisive role in the high-affinity biotin binding of rhizavidin. The structural
      description of a novel dimeric avidin-like molecule will greatly contribute to
      the design of improved and unique avidin derivatives for diversifying the
      capabilities of avidin-biotin technology.

PMID- 19111750
TI  - BolA inhibits cell elongation and regulates MreB expression levels.
AB  - The morphogene bolA is a general stress response gene in Escherichia coli that
      induces a round morphology when overexpressed. Results presented in this report
      show that increased BolA levels can inhibit cell elongation mechanisms. MreB
      polymerization is crucial for the bacterial cell cytoskeleton, and this protein
      is essential for the maintenance of a cellular rod shape. In this report, we
      demonstrate that bolA overexpression affects the architecture of MreB filaments.
      An increase in BolA leads to a significant reduction in MreB protein levels and
      mreB transcripts. BolA affects the mreBCD operon in vivo at the level of
      transcription. Furthermore, our results show that BolA is a new transcriptional
      repressor of MreB. The alterations in cell morphology induced by bolA seem to be
      mediated by a complex pathway that integrates PBP5, PBP6, MreB, and probably
      other regulators of cell morphology/elongation.

PMID- 19111751
TI  - Intracellularly expressed granulysin induced apoptosis in hepatoma cells and role
      of mitochondrial apoptotic pathway.
AB  - Extracellularly added recombinant granulysin was reported to kill mammalian
      target cells. The sites of actions and molecular mechanisms of granulysin in
      target cell killing, however, are presently unclear. In order to provide new
      insights into its potential mechanism of target cell damage, we here constructed
      recombinant plasmids carrying 9 kDa granulysin cDNA and examined effects of
      intracellularly expressed granulysin on the target hepatoma SMMC-7721 cells. The
      localization of intracellularly expressed granulysin was examined by fluorescence
      microscopy and confocal microscopy. Effects of granulysin on cell proliferation
      and apoptosis were measured by MTT (3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyl
      tetrazolium bromid) assay, flow cytometry and fluorescence microscopy,
      respectively. Changes of mitochondrial membrane potential were monitored by
      fluorescence microscopy. On the other hand, mitochondrial release of cytochrome c
      and apoptosis-inducing factor (AIF) was evaluated by Western blot and confocal
      microscopy. Intracellularly expressed granulysin was preferentially localized in
      cytoplasm, noticeably inhibited cell proliferation and induced cell death
      accompanied by reduced mitochondrial membrane potential, release of AIF and
      cytochrome c from mitochondria. Taken together, our findings demonstrate for the
      first time that localization and effect of intracellularly expressed granulysin
      on non-native cancer cells and indicate its potential utility in gene therapy for
      cancer.

PMID- 19111752
TI  - Multidrug-resistance-associated protein plays a protective role in menadione
      induced oxidative stress in endothelial cells.
AB  - AIMS: Menadione, a redox-cycling quinone known to cause oxidative stress, binds
      to reduced glutathione (GSH) to form glutathione S-conjugate. Glutathione S
      conjugates efflux is often mediated by multidrug-resistance-associated protein
      (MRP). We investigated the effect of a transporter inhibitor, MK571 (3-[[3-[2-(7
      chloroquinolin-2-yl)vinyl]phenyl]-(2
      dimethylcarbamoylethylsulfanyl)methylsulfanyl] propionic acid), on menadione
      induced oxidative stress in bovine aortic endothelial cells (BAECs). MAIN
      METHODS: BAECs were treated with menadione and MK571, and cell viability was
      measured. Modulation of intracellular GSH levels was performed with buthionine
      sulfoximine and GSH ethyl ester treatments. Intracellular superoxide was
      estimated by dihydroethidium oxidation using fluorescence microscopy or flow
      cytometry. Expression of MRP was determined by flow cytometry using phycoerythrin
      conjugated anti-MRP monoclonal antibody. KEY FINDINGS: Intracellular GSH
      depletion by buthionine sulfoximine promoted the loss of viability of BAECs
      exposed to menadione. Exogenous GSH, which does not permeate the cell membrane,
      or GSH ethyl ester protected BAECs against the loss of viability induced by
      menadione. The results suggest that GSH binds to menadione outside the cells as
      well as inside. Pretreatment of BAECs with MK571 dramatically increased
      intracellular levels of superoxide generated from menadione, indicating that
      menadione may accumulate in the intracellular milieu. Finally, we found that
      MK571 aggravated menadione-induced toxicity in BAECs and that MRP levels were
      increased in menadione-treated cells. SIGNIFICANCE: We conclude that MRP plays a
      vital role in protecting BAECs against menadione-induced oxidative stress,
      presumably due to its ability to transport glutathione S-conjugate.

PMID- 19111753
TI  - Pharmacological assessments of nitric oxide synthase isoforms and downstream
      diversity of NO signaling in the maintenance of thermal and mechanical
      hypersensitivity after peripheral nerve injury in mice.
AB  - Nitric oxide synthase (NOS) isoforms and NO downstream signal pathways involved
      spinally in the maintenance of thermal and mechanical hypersensitivity were
      assessed in a mouse model of neuropathic pain developing after partial ligation
      of the sciatic nerve. Intrathecal injection of the NOS inhibitor N(G)-nitro-l
      arginine methyl ester (l-NAME), the highly selective neuronal NOS (nNOS)
      inhibitor N(omega)-propyl-l-arginine and the potent selective inducible NOS
      (iNOS) inhibitor 2-amino-5,6-dihydro-6-methyl-4H-1,3-thiazine hydrochloride (AMT)
      exerted dose-dependent analgesic effects on thermal and mechanical
      hypersensitivity, which were assessed by the plantar and von Frey tests,
      respectively, suggesting that both nNOS and iNOS participate in producing NO to
      maintain neuropathic pain. Since the selective inhibitor of NO-sensitive guanylyl
      cyclase 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one (ODQ) and the guanosine 3',5'
      cyclic monophosphate (cGMP)-dependent protein kinase (PKG) inhibitor Rp-8-pCPT
      cGMPS intrathecally exerted dose-dependent analgesic effects on thermal and
      mechanical hypersensitivity, spinally released NO most likely stimulates the NO
      cGMP-PKG pathway. Moreover, the superoxide dismutase mimetic 4-hydroxy-2,2,6,6
      tetramethylpiperidine-1-oxyl (TEMPOL), a potent superoxide scavenger, reduced
      thermal and mechanical hypersensitivity when administered intrathecally,
      suggesting that spinal release of superoxide, which can then react with NO to
      produce peroxynitrite, also appears to mediate neuropathic pain. Finally,
      intrathecal injection of phenyl-N-tert-butylnitrone (PBN), a reactive oxygen
      species (ROS) scavenger, ameliorated thermal and mechanical hypersensitivity,
      thus further confirming the importance of ROS including NO and superoxide in the
      maintenance of neuropathic pain. Together, the present results demonstrate that
      NO, produced presumably via nNOS and iNOS in the spinal cord, mediates the
      maintenance of neuropathic pain following peripheral nerve injury through both
      the NO-cGMP-PKG and the NO-peroxynitrite pathways.

PMID- 19111754
TI  - Introduction: the end of sex as we once knew it.
AB  - This special issue of Physiology and Behavior is devoted to papers summarizing
      sex differences that are now recognized to include not only reproductive
      behaviors, but also non-reproductive processes and phenomena such as feeding,
      thirst, pain, sensory processes, mood, cognitive function, the effects of stress,
      and the propensity for drug abuse. The purpose of this brief introduction is to
      trace some of the main themes and historical highlights in the discovery that the
      entire nervous system appears to be a target of reproductive hormones, as well as
      being subject to developmentally programmed sex differences.

PMID- 19111755
TI  - Biochemistry and toxicology of toxins purified from the venom of the snake
      Bothrops asper.
AB  - The isolation and study of individual snake venom components paves the way for a
      deeper understanding of the pathophysiology of envenomings--thus potentially
      contributing to improved therapeutic modalities in the clinical setting--and also
      opens possibilities for the discovery of novel toxins that might be useful as
      tools for dissecting cellular and molecular processes of biomedical importance.
      This review provides a summary of the different toxins that have been isolated
      and characterized from the venom of Bothrops asper, the snake species causing the
      majority of human envenomings in Central America. This venom contains proteins
      belonging to at least eight families: metalloproteinase, serine proteinase, C
      type lectin-like, L-amino acid oxidase, disintegrin, DC-fragment, cystein-rich
      secretory protein, and phospholipase A(2). Some 25 venom proteins within these
      families have been isolated and characterized. Their main biochemical properties
      and toxic actions are described, including, in some cases, their possible
      relationships to the pathologic effects induced by B. asper venom.

PMID- 19111756
TI  - Atrial Fibrillation. Foreword.

PMID- 19111757
TI  - Atrial Fibrillation. Preface.

PMID- 19111759
TI  - Atrial fibrillation: a historical perspective.
AB  - Atrial fibrillation (AF) has undoubtedly become one of the most well-studied
      arrhythmias today in terms of pathophysiology and diagnostic and therapeutic
      (interventional) electrophysiology. Although it lends itself to an apparently
      easy diagnosis on the surface electrocardiography, myriad electromechanical
      mechanisms underlie its origin. We have now reached an era of technology that
      makes AF not only "treatable" but potentially "curable." This article aims at
      walking through the historical "corridors" and "mazes" that led to the present
      day understanding of this common yet complex arrhythmia.

PMID- 19111760
TI  - Current perceptions of the epidemiology of atrial fibrillation.
AB  - Atrial fibrillation (AF), an escalating dysrhythmia, is accountable for extensive
      population morbidity and mortality. In the United States, approximately 2.3
      million people are presently diagnosed with AF and it is estimated that this
      prevalence may increase to 5.6 million by 2050. Foremost predisposing risk
      factors for this dysrhythmia include advanced age and cardiovascular disease and
      its risk factors. The chief hazard of AF is embolic stroke, which is increased
      four- to fivefold, and in advanced age, it becomes a dominant stroke risk factor.
      AF also carries a doubled mortality rate.

PMID- 19111761
TI  - Genetics of atrial fibrillation.
AB  - Recent studies of AF have identified mutations in a series of ion channels;
      however, these mutations appear to be relatively rare causes of AF. A genome-wide
      association study has identified novel variants on chromosome 4 associated with
      AF, although the mechanism of action for these variants remains unknown.
      Ultimately, a greater understanding of the genetics of AF should yield insights
      into novel pathways, therapeutic targets, and diagnostic testing for this common
      arrhythmia.

PMID- 19111762
TI  - New concepts in atrial fibrillation: neural mechanisms and calcium dynamics.
AB  - Atrial fibrillation (AF) is a complex arrhythmia with multiple possible
      mechanisms. It requires a trigger for initiation and a favorable substrate for
      maintenance. Pulmonary vein myocardial sleeves have the potential to generate
      spontaneous activity, and this arrhythmogenic activity is surfaced by modulation
      of intracellular calcium dynamics. Direct autonomic nerve recordings in canine
      models show that simultaneous sympathovagal discharges are the most common
      triggers of paroxysmal atrial tachycardia and paroxysmal AF. Autonomic modulation
      as a potential therapeutic strategy has been targeted clinically and
      experimentally, but its effectiveness as an adjunctive therapeutic modality to
      catheter ablation of AF has been inconsistent. Further studies are warranted
      before application can be widely implied for therapies of clinical AF.

PMID- 19111764
TI  - Diagnosis and management of typical atrial flutter.
AB  - Typical atrial flutter (AFL) is a common atrial arrhythmia that may cause
      significant symptoms and serious adverse effects including embolic stroke,
      myocardial ischemia and infarction, and rarely a tachycardia-induced
      cardiomyopathy as a result of rapid atrioventricular conduction. As a result of
      the well-defined anatomic and electrophysiological substrate, and the relative
      pharmacologic resistance of typical AFL, radiofrequency catheter ablation has
      emerged in the past decade as a safe and effective first-line treatment. This
      article reviews the electrophysiology of typical AFL and the techniques currently
      used for its diagnosis and management.

PMID- 19111763
TI  - Information learned from animal models of atrial fibrillation.
AB  - Animal models of atrial fibrillation have taught us about mechanisms of this
      common disease. A variety of animal models exist, including models of lone atrial
      fibrillation and models of atrial fibrillation in the setting of heart failure,
      aging, or pericardial inflammation. This article reviews these various models.

PMID- 19111765
TI  - Postoperative atrial fibrillation.
AB  - Atrial fibrillation is a common arrhythmia that occurs after cardiac surgery. It
      is associated with an increase in morbidity, length of hospital stay and
      mortality. Patients who are at higher risk of postoperative atrial fibrillation
      should receive prophylactic treatment. Atrial fibrillation usually resolves
      spontaneously after heart rate is controlled; however, if patients are highly
      symptomatic or hemodynamically unstable, sinus rhythm should be restored by
      electrical or pharmacologic cardioversion.

PMID- 19111766
TI  - Atrial fibrillation in congestive heart failure: current management.
AB  - Atrial fibrillation (AF) and congestive heart failure are common conditions and
      each predisposes to the development of the other. Basic research using animal
      models of the two conditions continues to yield insights that may improve
      therapies. The role of medical therapies aimed at the underlying structural
      changes in AF continues to be a subject of ongoing studies. Cardiac
      resynchronization therapy is effective in appropriately selected patients with
      both sinus rhythm and AF. Catheter ablation is emerging as a potential
      alternative to antiarrhythmic drug therapy, but large randomized trials will be
      needed to assess its role.

PMID- 19111767
TI  - Electrical and pharmacologic cardioversion for atrial fibrillation.
AB  - This article describes electrical and pharmacologic cardioversion for atrial
      fibrillation and discusses indications for cardioversion and management of
      pericardioversion anticoagulation. Finally, management strategies are offered for
      immediate recurrence of atrial fibrillation and cardioversion failure.

PMID- 19111768
TI  - Drug therapy for atrial fibrillation.
AB  - Atrial fibrillation is the most frequently diagnosed arrhythmia. Prevalence
      increases with age, and the overall incidence is expected to increase as the
      population continues to age. Choice of pharmacologic therapy for atrial
      fibrillation depends on whether or not the goal of treatment is maintaining sinus
      rhythm or tolerating atrial fibrillation with adequate control of ventricular
      rates. Many new antiarrhythmic drugs are currently being tested in clinical
      trials. Drugs that target remodeling and inflammation have shown potential in
      prevention of atrial fibrillation, or as adjunctive therapy.

PMID- 19111770
TI  - The role of pacemakers in the management of patients with atrial fibrillation.
AB  - This article reviews the wide range of implantable device-based therapies (mainly
      pacemakers) that are being used in the management of atrial fibrillation (AF),
      atrial flutter, and atrial tachycardia. The role of pacemakers in the management
      of patients with AF and in the prevention of AF has been extensively studied.
      Based on well-designed prospective clinical trials, only a few of these
      strategies can be recommended for routine clinical use in related subpopulations.

PMID- 19111769
TI  - Anticoagulation: stroke prevention in patients with atrial fibrillation.
AB  - It is well recognized that during atrial fibrillation (AF), clots may form in the
      left atrium, which may embolize and cause ischemic stroke or systemic embolism.
      The presence of AF confers a fivefold increased risk for stroke. AF is the most
      common and important cause of stroke. This article considers the risks for and
      anticoagulation prophylaxis against embolic stroke in patients who have AF.

PMID- 19111771
TI  - Atrial fibrillation in patients with implantable defibrillators.
AB  - Atrial fibrillation (AF) is common in patients who have implantable
      defibrillators and presents some unique challenges and opportunities. AF burden
      can be assessed more accurately, allowing for evaluation of therapy efficacy
      (drugs or ablation). It remains to be shown whether home monitoring of
      defibrillators to detect and treat AF more quickly can reduce cardiovascular and
      stroke end points. One major goal will be to reduce inappropriate shocks from
      atrial fibrillation. Otherwise, the goals of therapy remain the same-reduction of
      symptoms (including heart failure exacerbation and inappropriate implantable
      cardioverter defibrillator therapies) by controlling rate or rhythm and
      anticoagulation for stroke prophylaxis.

PMID- 19111772
TI  - Catheter ablation of atrial fibrillation.
AB  - Atrial fibrillation is a common arrhythmia associated with significant morbidity,
      including angina, heart failure, and stroke. Medical therapy remains suboptimal,
      with significant side effects and toxicities, and a high recurrence rate.
      Catheter ablation or modification of the atrioventricular node with pacemaker
      implantation provides rate-control but exposes patients to the hazards associated
      with implantable devices and does nothing to reduce the risk for stroke.
      Pulmonary vein antrum isolation offers a nonpharmacologic means of restoring
      sinus rhythm, thereby eliminating the morbidity of atrial fibrillation and the
      need for antiarrhythmic drugs.

PMID- 19111773
TI  - Surgical approaches for atrial fibrillation.
AB  - For cardiac surgery patients presenting with atrial fibrillation (AF), surgeons
      offer an operation that corrects the structural heart disease and the AF. With
      this approach, it is estimated that surgeons will perform more than 10,000
      ablation procedures in 2008. Surgeons are developing minimally invasive
      techniques for stand-alone, epicardial ablation of AF. This article reviews the
      rationale for surgical ablation of AF, describes the classic maze procedure and
      its results, details new approaches to surgical ablation of AF, emphasizes the
      importance of management of the left atrial appendage, and considers challenges
      and future directions in the ablation of AF.

PMID- 19111775
TI  - Atrial fibrillation: unanswered questions and future directions.
AB  - The seminal demonstration of the role of pulmonary vein triggers in the
      pathogenesis of atrial fibrillation (AF) and the potential therapeutic role of
      catheter ablation to treat patients who have paroxysmal AF was provided just over
      a decade ago. This initial observation ushered in the modern era of catheter
      ablation to treat patients who have AF, and tremendous progress has been made in
      understanding its pathogenesis and the catheter approaches to treating this
      rhythm. This article reflects on some of the major unanswered questions about AF
      management, and the future technologic and investigational directions being
      explored in the nonpharmacologic management of AF.

PMID- 19111774
TI  - Atrial fibrillation: goals of therapy and management strategies to achieve the
      goals.
AB  - The primary goals in the management of patients who have atrial fibrillation are
      prevention of stroke and tachycardia-induced cardiomyopathy and amelioration of
      symptoms. Each patient presents to a physician with a specific constellation of
      symptoms and signs, but, fortunately, most patients can be assigned to broad
      categories for therapy. For some, anticoagulation and rate control suffice,
      whereas others require attempts to restore and maintain sinus rhythm. Physicians
      and patients should be willing to alter therapeutic plans if an initial strategy
      of rate or rhythm control is unsuccessful.

PMID- 19111776
TI  - The upper spatial limit for perception of displacement is affected by preceding
      motion.
AB  - The upper spatial limit D(max) for perception of apparent motion of a random dot
      pattern may be strongly affected by another, collinear, motion that precedes it
      [Mateeff, S., Stefanova, M., &. Hohnsbein, J. (2007). Perceived global direction
      of a compound of real and apparent motion. Vision Research, 47, 1455-1463]. In
      the present study this phenomenon was studied with two-dimensional motion
      stimuli. A random dot pattern moved alternately in the vertical and oblique
      direction (zig-zag motion). The vertical motion was of 1.04 degrees length; it
      was produced by three discrete spatial steps of the dots. Thereafter the dots
      were displaced by a single spatial step in oblique direction. Each motion lasted
      for 57ms. The upper spatial limit for perception of the oblique motion was
      measured under two conditions: the vertical component of the oblique motion and
      the vertical motion were either in the same or in opposite directions. It was
      found that the perception of the oblique motion was strongly influenced by the
      relative direction of the vertical motion that preceded it; in the "same"
      condition the upper spatial limit was much shorter than in the "opposite"
      condition. Decreasing the speed of the vertical motion reversed this effect.
      Interpretations based on networks of motion detectors and on Gestalt theory are
      discussed.

PMID- 19111777
TI  - JPSM affiliates with the AAHPM.

PMID- 19111778
TI  - Craniomandibular pain, bite force, and oral health-related quality of life in
      patients with jaw resection.
AB  - The present study evaluated the connection between temporomandibular disorders
      (TMD), maximum voluntary bite force and oral health-related quality of life
      (OHRQoL) in patients with oral cancer. Twenty-six prosthetically rehabilitated
      patients with partial resection of the upper and/or lower jaw with segmental
      mandibulectomy, with and without reconstruction, were examined. The examination
      comprised the Research Diagnostic Criteria for TMD (RDC/TMD), determination of
      the individual pain threshold, evaluation of the maximum voluntary bite force,
      and OHRQoL according to the Oral Health Impact Profile (OHIP) questionnaire. Male
      pain thresholds were significantly higher than female pain thresholds (P=0.003).
      Patients with maxillary resection showed higher pain threshold values than
      patients with (segmental) mandibulectomy. Bite force was significantly
      (P=0.000014) lower in resected jaw areas than in healthy ones. Patients with
      resections of the maxilla showed higher voluntary bite forces than patients with
      resections of the mandible; males showed higher bite forces than females. The
      prevalence of negative responses ("often"-2 and "very often"-1) on the OHIP items
      was 10.39%, whereas the prevalence of positive responses ("from time to time"-3,
      "seldom"-4, and "never"-5) was 89.60%. The prevalence for negative responses was
      2.46% in male patients and 8.07% in female patients. Patients with resections in
      the maxilla suffered from negative responses of 3.92%, patients with resection of
      the mandible of 6.64%. According to the OHIP, the psychological disposition of
      these patients clearly referred to coping mechanisms.

PMID- 19111779
TI  - The measurement of fatigue in chronic illness: a systematic review of
      unidimensional and multidimensional fatigue measures.
AB  - Fatigue is a common symptom associated with a wide range of chronic diseases. A
      large number of instruments have been developed to measure fatigue. An assessment
      regarding the reliability, validity, and utility of fatigue measures is time
      consuming for the clinician and researcher, and few reviews exist on which to
      draw such information. The aim of this article is to present a critical review of
      fatigue measures, the populations in which the scales have been used, and the
      extent to which the psychometric properties of each instrument have been
      evaluated to provide clinicians and researchers with information on which to base
      decisions. Seven databases were searched for all articles that measured fatigue
      and offered an insight into the psychometric properties of the scales used over
      the period 1980-2007. Criteria for judging the "ideal" measure were developed to
      encompass scale usability, clinical/research utility, and the robustness of
      psychometric properties. Twenty-two fatigue measures met the inclusion criteria
      and were evaluated. A further 17 measures met some of the criteria, but have not
      been tested beyond initial development, and are reviewed briefly at the end of
      the article. The review did not identify any instrument that met all the criteria
      of an ideal instrument. However, a small number of short instruments demonstrated
      good psychometric properties (Fatigue Severity Scale [FSS], Fatigue Impact Scale
      [FIS], and Brief Fatigue Inventory [BFI]), and three comprehensive instruments
      demonstrated the same (Fatigue Symptom Inventory [FSI], Multidimensional
      Assessment of Fatigue [MAF], and Multidimensional Fatigue Symptom Inventory
      [MFSI]). Only four measures (BFI, FSS, FSI, and MAF) demonstrated the ability to
      detect change over time. The clinician and researcher also should consider the
      populations in which the scale has been used previously to assess its validity
      with their own patient group, and assess the content of a scale to ensure that
      the key qualitative aspects of fatigue of the population of interest are covered.

PMID- 19111780
TI  - Review of physical activity measurement using accelerometers in older adults:
      considerations for research design and conduct.
AB  - OBJECTIVE: Accelerometers are being increasingly used in studies of physical
      activity (PA) among older adults, however the use of these monitors requires some
      specialized knowledge and up-to-date information on technological innovations.
      The purpose of this review article is to provide researchers with a guide to some
      commonly-used accelerometers in order to better design and conduct PA research
      with older adults. METHODS: A literature search was conducted to obtain all
      available literature on commonly-used accelerometers in older adult samples with
      specific attention to articles discussing research design. RESULTS: The use of
      accelerometers in older adults requires a basic understanding of the type being
      used, rationale for their placement, and attention to calibration when needed.
      The updated technology in some monitors should make study conduct less difficult,
      however comparison studies of the newer versus the older generation models will
      be needed. CONCLUSIONS: Careful considerations for design and conduct of
      accelerometer research as outlined in this review should help to enhance the
      quality and comparability of future research studies.

PMID- 19111781
TI  - Women's health: moving forward with the Jacobs Institute.

PMID- 19111782
TI  - Collaborating for change: creating a Women's Health Network.

PMID- 19111783
TI  - Facility-based maternal death review in three districts in the central region of
      Malawi: an analysis of causes and characteristics of maternal deaths.
AB  - PURPOSE: We sought to determine the causes and characteristics maternal deaths
      that occur in health facilities in Malawi. METHODS: Forty-three maternal deaths
      were reviewed in 9 hospitals in 3 districts in Central Malawi over a 1-year
      period. Causes and avoidable factors of maternal deaths were identified during
      the review, and recommendations made and implemented. MAIN FINDINGS: There were
      28 (65.1%) direct obstetric deaths and 15 (34.9%) indirect obstetric deaths. The
      major causes of maternal deaths were postpartum hemorrhage (25.6%), postpartum
      sepsis (16.3%), HIV/AIDS (16.3%), ruptured uterus (7.0%), complications of
      abortion (7.0%), anemia (7.0%), antepartum hemorrhage (4.7), and eclampsia (4.7).
      Two thirds of the women were referred either from another health facility (51.2%)
      or by a traditional birth attendant (TBA; 11.6%), and up to 79.1% were critically
      ill on admission. Four groups of factors that contributed to maternal deaths were
      identified: 1) health worker factors, 2) administrative factors, 3)
      patient/family factors, and 4) TBA factors. The major health worker factors were
      inadequate resuscitation (69.8%), lack of obstetric life-saving skills (60.5%),
      inadequate monitoring (55.8%), initial assessment incomplete (46.5%), and delay
      in starting treatment (46.5%). The most common administrative factor was lack of
      blood for transfusion (20.9%). The major problems encountered include shortage of
      staff and other resources, difficulty in maintaining anonymity, poor quality of
      data, and difficulty in implementing recommendations. CONCLUSION: Adequate
      training on obstetric life-saving skills, addressing HIV/AIDS, and raising
      community awareness could be important factors for reducing maternal mortality in
      Malawi and countries with similar socioeconomic profiles.

PMID- 19111784
TI  - Pregnancy losses in young Australian women: findings from the Australian
      Longitudinal Study on Women's Health.
AB  - INTRODUCTION: Little research has examined recognized pregnancy losses in a
      general population. Data from an Australian cohort study provide an opportunity
      to quantify this aspect of fecundity at a population level. METHOD: Participants
      in the Australian Longitudinal Study on Women's Health who were aged 28-33 years
      in 2006 (n = 9,145) completed up to 4 mailed surveys over 10 years. Participants
      were categorized according to the recognized outcome of their pregnancies,
      including live birth, miscarriage/stillbirth, termination/ectopic, or no
      pregnancy. RESULTS: At age 18-23, more women reported terminations (7%) than
      miscarriages (4%). By 28-33 years, the cumulative frequency of miscarriage (15%)
      was as common as termination (16%). For women aged 28-33 years who had ever been
      pregnant (n = 5,343), pregnancy outcomes were as follows: birth only (50%); loss
      only (18%); and birth and loss (32%), of which half (16%) were birth and
      miscarriage. A comparison between first miscarriage and first birth (no
      miscarriage) showed that most first miscarriages occurred in women aged 18-23
      years who also reported a first birth at the same survey (15%). Half (51%) of all
      first births and first miscarriages in women aged 18-19 ended in miscarriage.
      Early childbearers (<28 years) often had miscarriages around the same time period
      as their first live birth, suggesting proactive family formation. Delayed
      childbearers (32-33 years) had more first births than first miscarriages.
      CONCLUSION: Recognized pregnancy losses are an important measure of fecundity in
      the general population because they indicate successful conception and
      maintenance of pregnancy to varying reproductive endpoints.

PMID- 19111785
TI  - Maternity leave in the ninth month of pregnancy and birth outcomes among working
      women.
AB  - PURPOSE: The health effects of antenatal maternity leave have been scarcely
      evaluated. In California, women are eligible for paid benefits up to 4 weeks
      before delivery. We explored whether leave at > or =36 weeks gestation increases
      gestation and birthweight, and reduces primary cesarean deliveries among full
      time working women. METHODS: Drawing from a 2002--2003 nested case-control study
      of preterm birth and low birthweight among working women in Southern California,
      we compared a cohort of women who took leave (n = 62) or worked until delivery (n
      = 385). Models weighted for probability of sampling were used to calculate
      hazards ratios for gestational age, odds ratios (OR) for primary cesarean
      delivery, and multilinear regression coefficients for birthweight. MAIN FINDINGS:
      Leave-takers were similar to non-leave-takers on demographic and health
      characteristics, except that more clerical workers took leave (p = .02). Compared
      with non-leave-takers, leave-takers had almost 4 times lower odds of cesarean
      delivery after adjusting for covariates (OR, 0.27; 95% confidence interval [CI],
      0.08-0.94). Overall, there were no marked differences in length of gestation or
      mean birthweight. However, in a subgroup of women whose efforts outstripped their
      occupational rewards, gestation was prolonged (hazard ratio for delivery each day
      between 36 and 41 weeks, 0.56; 95% CI, 0.34-0.93). CONCLUSION: Maternity leave in
      late pregnancy shows promise for reducing cesarean deliveries and prolonging
      gestation in occupationally strained women.

PMID- 19111786
TI  - The relationship between sleep characteristics and fatigue in healthy postpartum
      women.
AB  - BACKGROUND: Postpartum sleep is a difficult and complicated concept to measure
      owing to the intrusive nature of research at a sensitive and private time for new
      families. Nurses often find themselves advising mothers on ways to improve sleep
      and reduce fatigue based on teachings that are not evidence based. The purpose of
      this secondary analysis of a larger study of postpartum fatigue patterns was to
      examine the relationship between sleep characteristics and postpartum fatigue
      during the first 6 weeks after delivery. METHODS: A prospective, longitudinal,
      descriptive study was conducted of 109 postpartum women. Sleep and fatigue were
      measured using a 16-item subjective sleep characteristics scale and a 30
      statement subjective fatigue instrument. Three measurement points were used: 1) 1
      2 days after delivery (before hospital discharge); 2) 2 weeks postpartum; and 3)
      6 weeks postpartum. RESULTS: Fatigue had a positive correlation with sleep
      disturbance at all three measurement points, indicating that higher levels of
      fatigue are associated with more disturbed sleep. No association was found
      between levels of fatigue and sleep supplementation. Levels of fatigue had a
      negative correlation with sleep effectiveness at all measurement points,
      indicating that the women were more fatigued if they perceived their sleep
      quality and adequacy to be poor or if they perceived the time spent sleeping to
      be short. CONCLUSIONS: To reduce fatigue, nurses should focus on exploring ways
      to reduce maternal sleep disturbance and improve maternal sleep effectiveness. It
      is unclear whether the age-old advice to "nap when your baby naps" is effective
      in reducing postpartum fatigue.

PMID- 19111787
TI  - Assessing sleep during pregnancy: a study across two time points examining the
      Pittsburgh Sleep Quality Index and associations with depressive symptoms.
AB  - BACKGROUND AND PURPOSE: Sleep quality seems to be an antecedent to depressive
      symptoms during pregnancy. We sought to 1) examine the psychometrics of the
      Pittsburgh Sleep Quality Index (PSQI) in pregnancy; 2) examine whether sleep
      quality predicted increases in depressive symptoms; and 3) compare PSQI scores
      across 3 or 2 levels of depressive symptoms. METHODS: Each of the 252
      participants completed the Beck Depression Inventory (short form) and a sleep
      quality measure at mid and late pregnancy. RESULTS: PSQI total scores showed good
      internal consistency and construct validity. An improved model of the internal
      structure of the PSQI in pregnancy was found with 1 factor labeled Sleep
      Efficiency, a second labeled Night and Daytime Disturbances, and an Overall Sleep
      Quality component associated with, but separate from, both of these 2 factors.
      Although PSQI scores showed moderate stability over time, sleep disturbance
      scores increased in late pregnancy. Importantly, PSQI prospectively predicted
      increases in depressive symptoms. CONCLUSIONS: Findings suggest that the PSQI is
      useful in pregnancy research. Findings also support the idea that sleep problems
      are prospective risk factors for increases in depressive symptoms during
      pregnancy. Practitioners are advised to screen for sleep quality during early
      pregnancy.

PMID- 19111788
TI  - Social, behavioral, and health care factors associated with recent HIV testing
      among sexually active non-Hispanic Black Women in the United States.
AB  - PURPOSE: We examined the prevalence of recent HIV testing among sexually active
      adult Black women in the United States and the social, behavioral, and health
      care factors associated with their receipt of these services. METHODS: Data from
      the 2002 National Survey of Family Growth were obtained. Our analyses focused on
      1,122 sexually active non-Hispanic Black women aged 18-44 years. Descriptive and
      multivariate logistic regression analyses were conducted on the total sample of
      women and on 3 subsamples of women, stratified by age group. MAIN FINDINGS: Only
      29% of the total sample of women reported recent HIV testing. Younger age and
      recent Pap testing were positively associated with recent HIV testing, whereas
      uninsurance and no recent pregnancy were negatively associated with recent HIV
      testing. Unique factors of recent HIV testing also were revealed for each age
      group. CONCLUSIONS: A low prevalence of Black women received HIV testing in 2001
      and 2002. Efforts to facilitate access to and utilization of health care are
      needed because these factors were associated with HIV testing. Public health
      messages to increase HIV testing among this vulnerable population of women also
      need to consider the factors unique to each age group.

PMID- 19111789
TI  - Financial and quality-of-life burden of dysfunctional uterine bleeding among
      women agreeing to obtain surgical treatment.
AB  - PURPOSE: In this study, we sought to 1) describe elements of the financial and
      quality-of-life burden of dysfunctional uterine bleeding (DUB) from the
      perspective of women who agreed to obtain surgical treatment; 2) explore
      associations between DUB symptom characteristics and the financial and quality-of
      life burden; 3) estimate the annual dollar value of the financial burden; and 4)
      estimate the most that could be spent on surgery to eliminate DUB symptoms for
      which medical treatment has been unsuccessful that would result in a
      $50,000/quality-adjusted life-year incremental cost-effectiveness ratio. METHODS:
      We collected baseline data on DUB symptoms and aspects of the financial and
      quality-of-life burden for 237 women agreeing to surgery for DUB in a randomized
      trial comparing hysterectomy with endometrial ablation. Measures included out-of
      pocket pharmaceutical expenditures, excess expenditures on pads or tampons, the
      value of time missed from paid work and home management activities, and health
      utility. We used chi2 and t tests to assess the statistical significance of
      associations between DUB characteristics and the financial and quality-of-life
      burden. The annual financial burden was estimated. RESULTS: Pelvic pain and
      cramps were associated with activity limitations and tiredness was associated
      with a lower health utility. Excess pharmaceutical and pad and tampon costs were
      $333 per patient per year (95% confidence interval [CI], $263-$403). Excess paid
      work and home management loss costs were $2,291 per patient per year (95% CI,
      $1847-$2752). Effective surgical treatment costing $40,000 would be cost
      effective compared with unsuccessful medical treatment. CONCLUSION: The financial
      and quality-of-life effects of DUB represent a substantial burden.

PMID- 19111790
TI  - Are women with functional limitations at high risk of underutilization of
      mammography screening?
AB  - OBJECTIVES: Women with functional limitations face obstacles in adhering to
      established mammography guidelines owing to personal factors and barriers within
      the health care system. Whereas some studies have focused on either physical or
      cognitive limitations that correlate with lower rates of cancer screening, this
      study examined multiple functional limitations (physical, psychological, and
      sociability) and mammography screening. METHODS: Data from the 2000 National
      Health Interview Survey were analyzed for 9,505 women aged > or =40 years. We
      hypothesized that women with functional limitations (physical, psychological,
      and/or sociability) are less likely to receive screening mammography. Access
      variables (insurance coverage and usual source of health care) and utilization
      variables (physician contact and receipt of clinical breast examination) were
      included. Using multiple logistic regression (MLR), we estimated the relative
      contribution of functional limitations on mammography use after accounting for
      sociodemographic characteristics and confounding variables. RESULTS: An estimated
      34.6% of women had physical limitations, 16.1% sociability limitations, and 8.1%
      psychological limitations. After controlling for all other variables, MLR
      analysis indicated that women with moderate or severe sociability limitations
      were less likely than their unimpaired counterparts to utilize mammography (odds
      ratio [OR], 0.62; 95% confidence interval [CI], 0.48-0.81). Interestingly, women
      with severe physical limitations were more likely than physically able women to
      utilize mammography screening (OR, 1.28; 95% CI, 1.07-1.53). Women with no
      insurance, no usual care, and no doctor's visit within the past year were
      substantially less likely to use mammography screening. CONCLUSIONS: Sociability
      limitations, lack of access to health care, and limited regular checkups played
      significant roles in underutilization of screening mammography.

PMID- 19111791
TI  - Some highlights of research on the effects of caudate nucleus lesions over the
      past 200 years.
AB  - This review describes experiments on the effects of caudate nucleus lesions on
      behavior in monkeys, cats and rats. Early work on monkeys and cats focused on the
      relationship of the caudate to the cortex in motor control, leading to the idea
      that the caudate serves to inhibit behaviors initiated by the cortex. However,
      investigation of this hypothesis with systematic behavioral testing in all three
      species did not support this idea; rather, these studies provided evidence that
      caudate lesions affect memory functions. Two main types of memory tasks were
      affected. One type involved reinforced stimulus-response (S-R) associations, the
      other involved spatial information, response-reinforcer contingencies, or working
      memory. Recent evidence, mainly from rats, suggests that the dorsolateral part of
      the caudoputamen is central to the processing and consolidation of memory for
      reinforced S-R associations, and that the more medial and anterior parts of the
      same structure are part of a neural circuit that (in some cases) also includes
      the hippocampus, and mediates relational information and certain forms of working
      memory. The possibility that the spatial distribution of the patch and matrix
      compartments within the caudoputamen underlies these regional differences is
      discussed.

PMID- 19111792
TI  - Role of dopamine receptors in the ventral tegmental area in conditioned fear.
AB  - The increased startle reflex in the presence of a stimulus that has been
      previously paired with footshock has been termed fear-potentiated startle (FPS)
      and is considered a reliable index of anxiety. Some studies have suggested an
      association between stressful situations and alterations in dopaminergic (DA)
      transmission. Many studies converge on the hypothesis that the mesocorticolimbic
      pathway, originating from DA neurons in the ventral tegmental area (VTA), is
      particularly sensitive to fear-arousing stimuli. The present study explored the
      involvement of VTA DA receptors in the acquisition and expression of conditioned
      fear to a light conditioned stimulus (CS). We evaluated the effects of intra-VTA
      administration of SKF 38393 (D(1) agonist), SCH 23390 (D(1) antagonist),
      quinpirole (D(2) agonist), and sulpiride (D(2) antagonist) on FPS. All drugs were
      administered bilaterally into the VTA (1.0 microg/0.2 microl/site). Locomotor
      activity/exploration and motor coordination were evaluated in the open-field and
      rotarod tests. None of the drugs produced significant effects on FPS when
      injected before conditioning, indicating that VTA DA receptors are not involved
      in the acquisition of conditioned fear to a light-CS. In contrast, when injected
      before the test session, quinpirole significantly reduced FPS, whereas the other
      drugs had no effect. Quinpirole's ability to decrease FPS may be the result of an
      action on VTA D(2) presynaptic autoreceptors that decrease dopamine levels in
      terminal fields of the mesocorticolimbic pathway. Altogether, the present results
      suggest the importance of VTA DA neurons in the fear-activating effects of
      Pavlovian conditioning. In addition to demonstrating the importance of
      dopaminergic mechanisms in the motivational consequences of footshock, the
      present findings also indicate that these neural circuits are mainly involved in
      the expression, rather than acquisition, of conditioned fear.

PMID- 19111793
TI  - In memoriam: a curious and careful gentleman--John P. Donohue, M.D.

PMID- 19111794
TI  - SUO/SBUR 2007 annual meeting proceedings: overview.

PMID- 19111795
TI  - 2007 Annual Meeting of the Society of Urologic Oncology and the Society of Basic
      Urologic Research: Introduction.

PMID- 19111797
TI  - The Ral GTPase pathway in metastatic bladder cancer: key mediator and therapeutic
      target.
AB  - Bladder cancer is a relatively common and strikingly costly malignancy. Here, we
      will focus on recent advances in our understanding of the molecular pathogenesis
      of metastatic bladder cancer, a stage of this disease curable in only a minority
      of patients. Our group has recently investigated the role of a class of small G
      proteins known as the Ras-like or Ral GTPases and their role in this disease.
      These signaling proteins, regulated by the Ras pathway and other mechanisms, have
      been shown to be necessary for key cellular phenotypes associated with
      transformation or cancer progression in diverse cancer systems. In bladder cancer
      we have observed that these GTPases are overexpressed, are necessary for key
      phenotypes in models of bladder cancer progression, and finally, are essential
      for the regulation of expression of key molecules, including the prognostic
      marker and cell surface GPI-linked glycoprotein, CD24. These findings are
      reviewed here and suggest that Ral GTPases and their downstream pathways
      constitute key mediators of bladder cancer progression and may include targets
      for future therapeutic strategies.

PMID- 19111796
TI  - Mechanisms mediating androgen receptor reactivation after castration.
AB  - Androgen deprivation is still the standard systemic therapy for metastatic
      prostate cancer (PCa), but patients invariably relapse with a more aggressive
      form of PCa termed hormone refractory, androgen independent, or castration
      resistant PCa (CRPC). Significantly, the androgen receptor (AR) is expressed at
      high levels in most cases of CRPC, and these tumors resume their expression of
      multiple AR-regulated genes, indicating that AR transcriptional activity becomes
      reactivated at this stage of the disease. The molecular basis for this AR
      reactivation remains unclear, but possible mechanisms include increased AR
      expression, AR mutations that enhance activation by weak androgens and AR
      antagonists, increased expression of transcriptional coactivator proteins, and
      activation of signal transduction pathways that can enhance AR responses to low
      levels of androgens. Recent data indicate that CRPC cells may also carry out
      intracellular synthesis of testosterone and DHT from weak adrenal androgens and
      may be able to synthesize androgens from cholesterol. These mechanisms that
      appear to contribute to AR reactivation after castration are further outlined in
      this review.

PMID- 19111798
TI  - Oncogenic activation of androgen receptor.
AB  - BACKGROUND: There is considerable evidence implicating the aberrant activation or
      "reactivation" of androgen receptor in the course of androgen-ablation therapy as
      a potential cause for the development of castration-resistant prostate cancer.
      Several non-mutually exclusive mechanisms including the inappropriate activation
      of androgen receptor (AR) by non-steroids have been postulated. The present work
      is aimed to understand the role of neuropeptides released by neuroendocrine
      transdifferentiated prostate cancer cells in the aberrant activation of AR.
      OBJECTIVES: The study was designed to study how neuropeptides such as gastrin
      releasing peptide activate AR and to define the crucial signal pathways involved,
      in the hope to identify therapeutic targets. METHODS AND MATERIALS: Androgen
      dependent LNCaP cell line was used to study the effects of bombesin/gastrin
      releasing peptide on the growth of the cell line and the transactivation of AR.
      The neuropeptide was either added to the media or introduced as a transgene in
      LNCaP cells to study its paracrine or autocrine effect on LNCaP growth under
      androgen-deprived conditions. The activation of AR was monitored by reporter
      assay, chromatin immunoprecipitation (ChIP) of AR, translocation into the nucleus
      and cDNA microarray of the AR response genes. RESULTS: Bombesin/gastrin releasing
      peptides induce androgen-independent growth of LNCaP in vitro and in vivo. It
      does so by activating AR, which is accompanied by the activation of Src tyrosine
      kinase and its target c-myc oncogene. The bombesin or Src-activated AR induces an
      overlapping set of AR response genes as androgen, but they also a unique set of
      genes. Intriguingly, the Src-activated and androgen-bound ARs differ in their
      binding specificity toward AR response elements, indicating the receptors
      activated by these 2 mechanisms are not conformationally identical. Finally, Src
      inhibitor was shown to effectively block the activation of AR and the growth
      effects induced by bombesin. CONCLUSION: The results showed that AR can be
      activated by neuropeptide, a ligand for G-protein coupled receptor, in the
      absence of androgen. The activation goes through Src-tyrosine kinase pathway, and
      tyrosine kinase inhibitor is a potentially useful adjunctive therapy during
      androgen ablation.

PMID- 19111800
TI  - Exclusion of inflammation in the differential diagnosis of an elevated prostate
      specific antigen (PSA).
AB  - Prostate inflammation can lead to an elevation in the serum PSA concentration and
      confound the use of PSA kinetics. This can have considerable clinical
      consequences, since these measurements form the basis for important clinical
      decisions. Thus, there has been investigation into ways to decrease the
      confounding from inflammation, including repeat PSA measurements after a period
      of observation or a course of empiric antibiotics. This article reviews the
      evidence about elevations in PSA due to prostatitis and describes the controversy
      over the optimal approach to reduce its confounding impact on prostate cancer
      screening.

PMID- 19111799
TI  - The Coffey Lecture: steroidogenic enzyme inhibitors and hormone dependent cancer.
AB  - OBJECTIVES: To improve treatment for patients with breast and prostate cancer.
      METHODS: A number of novel inhibitors of steroidogenic enzymes have been
      developed. Their biological effects have been evaluated in a variety of
      preclinical models. Aromatase (estrogen synthetase) inhibitors have now been
      extensively tested in clinical trials in breast cancer patients. Inhibitors of
      17alpha-hydroxylase/lyase have also been studied in preclinical models and are
      beginning trials in prostate cancer patients. RESULTS: The enzyme aromatase
      (CYP19) has proven to be an important therapeutic target. Inhibitors of aromatase
      (AIs) are showing greater benefit than antiestrogens in the treatment of breast
      cancer. Although effective in other conditions in both women and men, AIs have
      not been useful in benign prostatic hypertrophy or prostate cancer. However
      inhibitors of 17alphahydroxylase/lyase (CYP17) to block synthesis of androgens
      may be effective for prostate cancer. Recent clinical trials with abiraterone and
      preclinical studies with other novel CYP17 inhibitors, which also interact with
      the androgen receptor and cause its down-regulation, could provide a new approach
      for treating this disease. In further studies, we optimized treatment with
      aromatase inhibitors and antiestrogens utilizing an intratumoral aromatase
      xenograft model. AIs were more effective and sustained growth inhibition was
      longer than antiestrogens. However, inevitably tumors eventually began to grow
      despite continued treatment. Analysis of breast tumors from mice treated with
      letrozole revealed up-regulation of HER-2 and MAP Kinase signaling proteins and
      down-regulation of the estrogen receptor. Our studies showed that tumors adapt to
      AI treatment by activating alternate signaling pathways, thus enabling them to
      proliferate in the absence of estrogen. When mice bearing resistant tumors were
      treated with trastuzumab, the anti-HER-2 antibody (herceptin), HER-2 was
      decreased in the tumor but the estrogen receptor and aromatase were restored.
      Tumor growth was significantly inhibited by treatment with trastuzumab in
      addition to letrozole. CONCLUSIONS: Aromatase inhibitors are proving to be an
      effective new class of agents for the treatment of breast cancer. Compounds
      inhibiting 17alphahydroxylase/lyase have potential for the treatment of prostate
      cancer. Our results suggest that strategies to overcome resistance to these types
      of agents can restore sensitivity of the tumors to hormone therapy.

PMID- 19111801
TI  - Outcomes for intermediate risk prostate cancer: are there advantages for surgery,
      external radiation, or brachytherapy?
AB  - The treatment of localized prostate cancer remains controversial because of the
      lack of conclusive well-controlled or randomized studies comparing outcome of
      various forms of radiotherapy (RT) to radical prostatectomy (RP). We review
      recent results from an institutional database and prospective quality of life
      study comparing cancer-related and quality of live (QOL) outcomes among different
      treatment modalities for intermediate risk prostate cancer. The results suggest
      similar short-term survival but domain-specific effects on QOL after treatment
      with radical prostatectomy, brachytherapy, or external beam radiotherapy.

PMID- 19111802
TI  - Optimizing outcomes at every stage of bladder cancer: do we practice it?
AB  - Defining the best practices in treating any disease can lead to optimal
      treatment. Establishing these best practices is difficult, and relies on clinical
      trials, expert opinion, and consensus decisions. Bladder cancer is a
      heterogeneous disease that can be either relatively benign or highly malignant
      depending on the grade and stage of the tumor. Determining the best practices for
      bladder cancer is based on the stage, grade, and presentation of the cancer.
      Herein we identify four clinical scenarios involving bladder cancer and discuss
      whether best practice guidelines are available for these clinical scenarios, and
      if so, how often do we follow these guidelines.

PMID- 19111803
TI  - Are we underutilizing minimally invasive approaches for upper tract urothelial
      carcinoma?
AB  - Endoscopy should be considered a first-line treatment for technically resectable
      low grade/stage upper tract urothelial carcinoma, even in the presence of a
      normal contralateral kidney. Endoscopy also should be considered an alternative
      to nephroureterectomy and end stage renal disease in patients with a solitary
      kidney or other imperative indications for nephron sparing, even in the presence
      of high-risk upper tract urothelial carcinoma. In both cases, however, endoscopic
      management is acceptable only if the patient and the urologist accept the
      rigorous surveillance regimens and the frequent need for repeated treatments.

PMID- 19111804
TI  - The continued debate: intermittent vs. continuous hormonal ablation for
      metastatic prostate cancer.
AB  - OBJECTIVES: To summarize the debate regarding use of intermittent androgen
      suppression therapy in the treatment of prostate cancer originally presented at
      the 2007 Spring Meeting of the Society of Urologic Oncology. METHODS: The debate
      was framed within the context of known toxicities of therapy and impact on
      quality of life. Arguments for and against IAS were summarized. RESULTS: IAS
      appears to be a reasonable treatment approach for men with advanced prostate
      cancer except those with high risk features including PSA > 20, or bone
      metastatic disease. Men with TxN1-3M0 who are sexually active, compliant to close
      follow-up, or who do not tolerate the side effects of androgen ablation can be
      considered for IAS as long as they realize it is investigational. There is not a
      clear consensus upon duration of treatment, interval between treatment cycles, or
      appropriate PSA nadir, but it does appear that PSA nadir > 4 ng/ml may predict a
      poor outcome. Based on time to PSA nadir and changes in expression of
      proliferation markers staining, treatment duration of 6 to 9 months is
      recommended prior to stopping therapy. Trigger points for restarting therapy are
      individualized, and factors that are considered include pretreatment PSA levels,
      stage, PSA velocity, presence of symptoms, and tolerance of androgen ablation
      therapy. CONCLUSIONS: IAS should be considered in the management of men with
      advanced prostate cancer and no evidence of bone metastases. While intermittent
      therapy is feasible and offers potential improvement in quality of life, it is
      not yet shown that it reverses the long-term side effects of androgen
      suppression.

PMID- 19111805
TI  - Post-radical prostatectomy management options for the positive surgical margin:
      argument for adjuvant radiotherapy.
AB  - The debate on the optimal management for patients with positive surgical margins
      following radical prostatectomy is on-going. From published evidence, we
      established that adjuvant XRT has acceptable, well-tolerated transient toxicity
      that dissipates with time. We examined the best conditions for optimal results
      from adjuvant radiotherapy (XRT), when the prostate-specific antigen (PSA) level
      is very low or undetectable, i.e., in the true adjuvant setting. We also examined
      the substantial amount of evidence from nonrandomized series, almost unanimously
      being in favor of early XRT. Most importantly, there is robust Level I evidence
      from well-executed randomized clinical trials reporting superior biochemical
      relapse-free and progression-free survival with early adjuvant XRT for patients
      with positive margins.

PMID- 19111806
TI  - Positive surgical margins: the argument for androgen deprivation and
      chemotherapy.
AB  - Management of patients with positive surgical margins after radical prostatectomy
      is a complex and debatable issue. It is clear, however, that many of these
      patients have high-risk disease characteristics. Because of a significant risk of
      relapse, patients with positive surgical margins and high-risk disease
      characteristics should be offered the option of participating in clinical trials
      evaluating the role of adjuvant therapy. A distinction between the concepts of
      adjuvant versus salvage therapy is made and the rationale for the use of androgen
      deprivation therapy, chemotherapy, or a combination in the adjuvant setting is
      discussed in the context of the on-going phase III trials in the United States.

PMID- 19111807
TI  - Post-radical prostatectomy management options for positive surgical margins:
      argument for observation.
AB  - The screening zeal for prostate cancer in the PSA era resulted in and continues
      to produce an unprecedented number of men who have clinically localized prostate
      cancer seeking radical prostatectomy. Even before the advent of robotic
      laparoscopic-assisted radical prostatectomy (RALP), the topic of positive margins
      was hot. However, now it is even more contested in the era of the "RALP learning
      curve", the era of "The role of the experienced surgeon," and the era of the
      "well-informed Internet-savvy patient." The typical modern-era man with localized
      prostate cancer has very high expectations. He may be a younger Baby-Boomer who
      has been used to getting things his way and has been raised in a consumer-driven
      society. He is diagnosed with prostate cancer and his knowledge-seeking behavior
      then may be analogous to "finding religion." He, and/or his family, seeks "the
      best" surgeon and "the best" method of surgery, and he is expecting the trifecta
      outcome of cure, continence, and potency. The first episode to potentially
      deflate his sails is when the surgical pathology report returns and shows a
      positive margin.

PMID- 19111808
TI  - Optimal timing of chemotherapy in androgen independent prostate cancer.
AB  - PURPOSE: To interpret available docetaxel clinical trial data in order to define
      optimal timing of the initiation of chemotherapy in androgen independent prostate
      cancer (AIPC). MATERIALS AND METHODS: Published literature on the natural history
      of nonmetastatic AIPC was reviewed. Phase III clinical trials using docetaxel
      based therapy were analyzed as well as their associated quality of life (QOL)
      findings. Trials using docetaxel in earlier stage of the disease, as well those
      using novel agents were examined. RESULTS: Based on one report, non-metastatic
      AIPC is relatively indolent, and there is currently no evidence that supports the
      use of chemotherapy in this disease subset. The results of TAX 327 and SWOG 9916
      demonstrate that chemotherapy is indicated for metastatic AIPC. However, based on
      available data, more than one hormonal maneuver can be offered to patients before
      chemotherapy is initiated. Timing of docetaxel therapy can further be
      individualized based on risk, clinical status, and patients' values and
      preferences. Building on the success of docetaxel, several novel agents that
      target different pathways are being tested in combination with, or as an
      alternative to, docetaxel-based therapy in Phase III clinical trials.
      CONCLUSIONS: Currently, docetaxel therapy should be reserved for patients with
      metastatic AIPC who have progressed despite one or more hormonal therapies. In
      most patients, more than one hormonal treatment can be offered before
      chemotherapy is initiated. Studies that test the efficacy of chemotherapy early
      in the natural history of prostate cancer are under way or are planned.

PMID- 19111829
TI  - Acute hypertriglyceridaemia in humans increases the triglyceride content and
      decreases the anti-inflammatory capacity of high density lipoproteins.
AB  - INTRODUCTION: Post-prandial hypertriglyceridaemia is a risk factor for
      cardiovascular disease, although the underlying mechanisms remain unclear. High
      density lipoproteins (HDL) have been shown to be atheroprotective, in part
      through attenuation of vascular inflammation. In this study, the influence of
      acute hypertriglyceridaemia on the composition and anti-inflammatory properties
      of HDL was investigated. METHODS: Eight fasting healthy male subjects (34+/-2
      years) received 20% Intralipid (15 mg/kg/h) or saline, on separate occasions in
      random order. At baseline and 60 min post-infusion, the total HDL fraction was
      isolated and its chemical composition determined. HDL were added to TNF-alpha
      stimulated human coronary artery endothelial cells and VCAM-1 and ICAM-1
      expression was determined by flow cytometry. RESULTS: Serum triglyceride (97.4+/
      8.5mg/dL baseline, 283.2+/-35.4 mg/dL post-infusion, p<0.001) and HDL
      triglyceride content (3.8+/-0.5% HDL mass baseline, 5.3+/-0.9% HDL mass post
      infusion, p<0.05) increased significantly after Intralipid infusion. HDL post
      Intralipid were significantly less anti-inflammatory compared with control (e.g.
      at 8 microM apoA-I, %VCAM-1 expression 54+/-5 post-saline, 73+/-4 post
      Intralipid, p=0.01; %ICAM-1 expression 94+/-1 post-saline, 99.4+/-0.6 post
      Intralipid, p<0.01). There was also a significant correlation between HDL
      triglyceride content and VCAM-1 expression (R=0.70, p=0.005); as well as between
      plasma triglyceride levels and both VCAM-1 (R=0.71, p<0.005) and ICAM-1
      expression (R=0.80, p<0.005). CONCLUSION: Acute hypertriglyceridaemia, simulating
      the post-prandial state, results in triglyceride-rich HDL with impaired anti
      inflammatory capacity.

PMID- 19111830
TI  - Inhibited atherosclerotic plaque formation by local administration of
      magnetically labeled endothelial progenitor cells (EPCs) in a rabbit model.
AB  - PURPOSE: To investigate whether atherosclerosis can be prevented by magnetically
      labeled endothelial progenitor cells (EPCs) in rabbits. MATERIALS AND METHODS:
      EPCs derived from rabbit periphery blood were labeled with a superparamagnetic
      iron oxide (SPIO) agent Fe(2)O(3)-poly-L-lysine (Fe(2)O(3)-PLL). Rabbit
      atherosclerosis was induced by high-cholesterol-diet following balloon injury via
      catheterization of right common carotid artery (RCCA). Fe(2)O(3)-PLL labeled EPCs
      (2 x 10(6)) and media were allowed to interact with the RCCA for 25 min in EPC
      treated rabbits (n=14) and control rabbits (n=7) animals respectively. MRI was
      performed with a 1.5T-magnet to measure RCCA signal intensity (SI) and caliber at
      week 1, 2, 3, 6, 12, and 15 with animals euthanized in groups for histopathology.
      RESULTS: In EPC-treated rabbits, T(2)(*)-weighted MRI showed SI loss in RCCA at
      week 1 and 2 followed by normalization after week 3. MRI outcomes corresponded
      well to findings of Prussian blue staining. MRI at week 6, 12 and 15 showed
      little stenosis of RCCA in EPC-treated rabbits, but moderate to severe stenoses
      in control rabbits. Histology at week 15 revealed significantly thinner RCCA wall
      (277.62 microm vs. 382.95 microm, P=0.026), greater internal diameter (913.33
      microm vs. 789.64 microm, P=0.037) and smaller plaque (398.60mm(2) vs. 597.70
      mm(2), P=0.047) in EPC-treated rabbits relative to control rabbits. CONCLUSION:
      Atherosclerosis at RCCA was inhibited by SPIO-labeled EPCs, which was depicted
      with a clinical MRI scanner over 2 weeks after cell administration, suggesting
      that EPCs may play a role in restoration of endothelial injury and prevention of
      atherosclerosis.

PMID- 19111831
TI  - Targeted overexpression of the human urotensin receptor transgene in smooth
      muscle cells: effect of UT antagonism in ApoE knockout mice fed with Western
      diet.
AB  - Urotensin II (UII) and its receptor UT are upregulated in the pathological
      setting of various cardiovascular diseases including atherosclerosis. However,
      their exact role in atherosclerosis remains to be determined. In the present
      study we used four strains of mice; wild-type (WT), UT(+) (a transgenic strain
      expressing human UT driven by the alpha-smooth muscle-specific, SM22, promoter),
      ApoE knockout (ko), and UT(+)/ApoE ko. All animals were fed high fat diet for 12
      weeks. Western blot analysis revealed a significant increase in aortic UT
      expression in UT(+) relative to WT mice (P<0.05). Aortas of ApoE ko mice
      expressed comparable UT protein level to that of UT(+). Immunohistochemistry
      revealed the presence of strong expression of UT and UII proteins in the atheroma
      of UT(+), ApoE ko and UT(+)/ApoE ko mice, particularly in foam cells. Serum
      cholesterol and triglyceride levels were significantly increased in ApoE ko and
      in UT(+)/ApoE ko but not in UT(+) mice when compared to WT mice (P<0.0001).
      Analysis of aortas showed a significant increase in atherosclerotic lesion in the
      UT(+), ApoE ko and UT(+)/ApoE ko compared to WT mice (P<0.05). Oral
      administration of the UT receptor antagonist SB-657510A (30 microg/Kg/day gavage)
      for 10 weeks in a group of ApoE ko mice fed on high fat diet resulted in a
      significant reduction of lesion (P<0.001). SB-657510A also significantly reduced
      ACAT-1 protein expression in the atherosclerotic lesion of ApoE ko mice (P<0.05).
      The present findings demonstrate an important role for UT in the pathogenesis of
      atherosclerosis. The use of UT receptor antagonists may provide a beneficial tool
      in the management of this debilitating disease process.

PMID- 19111832
TI  - Rosuvastatin reduces atherosclerotic lesions and promotes progenitor cell
      mobilisation and recruitment in apolipoprotein E knockout mice.
AB  - Statins enhance incorporation of bone marrow-derived cells into experimental
      neointimal lesions. However, the contribution of progenitor cells to progression
      of spontaneous atherosclerotic plaques, and the possible modulatory role of
      statins in this process, remain poorly understood. We compared the effects of
      rosuvastatin (1 and 10mg/kg BW) and pravastatin (10mg/kg) on progenitor cell
      mobilisation, recruitment into atherosclerotic plaques, and lesion growth.
      Statins were administered over 8 weeks to apolipoprotein E knockout mice on
      atherogenic diet. In addition, mice were lethally irradiated, followed by
      transplantation of bone marrow from LacZ transgenic mice. Rosuvastatin reduced
      lesion area and intima-to-media ratio at the brachiocephalic artery compared to
      vehicle, while both parameters were not significantly altered by pravastatin.
      Rosuvastatin also augmented endothelialisation (P<0.05) and reduced the smooth
      muscle cells (SMC) content (P=0.042) of lesions. Numbers of c-kit, sca-1 and flk
      1, sca-1 double-positive progenitor cells were significantly increased in
      rosuvastatin compared to control-treated mice, both in the bone marrow and the
      peripheral blood. Similarly, the number of spleen-derived acLDL, lectin double
      positive progenitor cells (P=0.001) and colony-forming units (P=0.0104) was
      significantly increased in mice treated with rosuvastatin compared to vehicle
      alone. In the bone marrow, increased Akt and p42/44 MAP kinase phosphorylation
      and upregulated SDF1alpha mRNA expression were observed. Importantly,
      rosuvastatin treatment also increased the plasma levels of c-kit ligand
      (P=0.003), and the number of c-kit-positive cells within atherosclerotic lesions
      (P=0.041). Our findings suggest that rosuvastatin reduces the size of
      atherosclerotic plaques, and this effect appears to involve progenitor cell
      mobilisation and recruitment into vascular lesions.

PMID- 19111833
TI  - Adiponectin and inducible ischemia in patients with stable coronary heart
      disease: data from the Heart and Soul study.
AB  - OBJECTIVE: Elevated concentrations of adiponectin are associated with a favorable
      metabolic profile but also with adverse cardiovascular outcomes. This apparent
      discrepancy has raised questions about whether adiponectin is associated with an
      increased or decreased risk of coronary heart disease (CHD). We sought to
      determine whether higher adiponectin levels are associated with exercise-induced
      ischemia in patients with stable CHD. METHODS AND RESULTS: We measured total
      serum adiponectin concentrations and evaluated exercise-induced ischemia by
      stress echocardiography in a cross-sectional study of 899 outpatients with
      documented stable CHD. Of these, 217 (24%) had inducible ischemia. Although
      adiponectin levels correlated negatively with diabetes prevalence, body mass
      index, serum insulin, fasting glucose, low-density lipoprotein cholesterol, and
      triglycerides and positively with high-density lipoprotein cholesterol (all
      P<0.005), elevated adiponectin concentrations were also associated with a greater
      risk of inducible ischemia. Each standard deviation (0.08 microg/mL) increase in
      log adiponectin was associated with a 35% greater odds of inducible ischemia
      (unadjusted odds ratio 1.35; 95% confidence interval 1.15-1.57; P=0.0002).
      Although attenuated, this association remained present after multivariable
      adjustment for traditional cardiovascular risk factors and other measures of
      cardiac function (adjusted odds ratio 1.21; 95% confidence interval 1.02-1.43;
      P=0.03). CONCLUSIONS: Elevated concentrations of adiponectin are independently
      associated with inducible ischemia in patients with stable CHD. These findings
      raise the possibility that the presence of chronic inducible ischemia may alter
      the cardio-protective effects afforded by adiponectin secretion in the healthy
      population.

PMID- 19111834
TI  - Abnormalities of endothelium-dependent responses in mesenteric arteries from
      Otsuka Long-Evans Tokushima Fatty (OLETF) rats are improved by chronic treatment
      with thromboxane A2 synthase inhibitor.
AB  - Thromboxane A(2) (TXA(2)) is thought to contribute to the development of diabetic
      complications. We tested the hypothesis that the impaired endothelial function
      seen in Otsuka Long-Evans Tokushima Fatty (OLETF) rats (a type 2 diabetic model)
      might be improved by chronic treatment with ozagrel, a TXA(2) synthase inhibitor.
      In mesenteric arteries from OLETF rats (40-46 weeks old) [vs. those from age
      matched Long-Evans Tokushima Otsuka (LETO) rats]: (1) ACh-induced endothelium
      dependent relaxation, NO-mediated relaxation, and endothelium-derived
      hyperpolarizing factor (EDHF)-type relaxation were all reduced; (2) ACh-induced
      cyclooxygenase-dependent contraction was enhanced; (3) endothelium-derived
      contracting factor (EDCF)-mediated contraction was enhanced; (4) ACh-stimulated
      nitrite production was reduced but the nitrate/nitrite ratio was increased; and
      (5) ACh-stimulated production of TXA(2) was increased. Chronic treatment with
      ozagrel (100mg/kg/day for 4 weeks, starting when they were 36-42 weeks of age)
      partly corrected the above abnormalities. These results suggest that ozagrel has
      normalizing effects on endothelial functions in OLETF mesenteric arteries, at
      least partly by increasing endothelium-derived relaxing factors (i.e., NO and
      EDHF) signaling and reducing EDCF signaling.

PMID- 19111835
TI  - Sterilization of Bacillus pumilus spores using supercritical fluid carbon dioxide
      containing various modifier solutions.
AB  - Supercritical fluid carbon dioxide (SF-CO(2)) with small amounts of chemical
      modifier(s) provides a very effective sterilization technique that should be
      useful for destroying microorganism on heat-sensitive devices such as instruments
      flown on planetary-bound spacecraft. Under a moderate temperature (50 degrees C)
      and pressure (100 atm), spores of Bacillus pumilus strains ATCC 7061 and SAFR 032
      can be effectively inactivated/eliminated from metal surfaces and small
      electronic devices in only 45 min using optimized modifier concentrations.
      Modifiers explored in this study included hydrogen peroxide (H(2)O(2)), tert
      butyl hydroperoxide, formic acid, and Triton X-100. During sterilization
      procedure the modifiers were continuously added to SF-CO(2) in either methanol or
      water at controlled concentrations. The lowest effective concentrations were
      established for each modifier. Complete elimination of both types of B. pumilus
      endospores occurred with an optimal modifier addition of either or 10% methanol
      containing 12% H(2)O(2) or 12% tert-butyl hydroperoxide in SF-CO(2), or a mixture
      of 6% H(2)O(2) and 6% tert-butyl hydroperoxide. Using water as the carrier of SF
      CO(2) modifier, the complete elimination of spores viability of both B. pumilus
      strains occurred with an addition of either 3.3% water containing 3% H(2)O(2), or
      3.3% water containing 10% methanol and 0.5% formic acid, or 3.3% water containing
      10% methanol, 1% formic acid and 2% H(2)O(2).

PMID- 19111836
TI  - Editorial on "Sense and nonsense of high-temperature liquid chromatography" by S.
      Heinisch and J.-L. Rocca.

PMID- 19111837
TI  - Activity of the AtMRP3 promoter in transgenic Arabidopsis thaliana and Nicotiana
      tabacum plants is increased by cadmium, nickel, arsenic, cobalt and lead but not
      by zinc and iron.
AB  - Characterization of the function, regulation and metal-specificity of metal
      transporters is one of the basic steps needed for the understanding of transport
      and accumulation of toxic metals and metalloids by plants. In this work GUS was
      used as a reporter for monitoring the activity of the promoter of the AtMRP3 gene
      from Arabidopsis thaliana, a gene encoding an ABC-transporter, expression of
      which is induced by heavy metals. The AtMRP3 promoter-GUS fusion expression
      cassette was introduced into the genome of two model plants, A. thaliana and
      Nicotiana tabacum. The promoter induces GUS activity in the roots as well as in
      the shoots upon metal exposure. Similar responses of the AtMRP3 promoter to the
      presence of the selected metals was observed in both plant species. Cadmium,
      nickel, arsenic, cobalt and lead strongly activated the transcription of the
      reporter gene, while zinc and iron had no impact. The AtMRP3 promoter thus seems
      to be a useful new tool in designing plants that can be used for biomonitoring of
      environmental contaminations.

PMID- 19111838
TI  - Establishment of a high content assay for the identification and characterisation
      of bioactivities in crude bacterial extracts that interfere with the eukaryotic
      cell cycle.
AB  - High content microscopy as a screening tool to identify bioactive agents has
      provided researchers with the ability to characterise biological activities at
      the level of single cells. Here, we describe the development and the application
      of a high content screening assay for the identification and characterisation of
      cytostatic bioactivities from Myxobacteria extracts. In an automated microscopy
      assay Sf9 insect cells were visualised utilising the stains bisbenzimide Hoechst
      33342, calcein AM, and propidium iodide. Imaging data were processed by the ScanR
      Analysis-software to determine the ploidy and vitality of each cell and to
      quantify cell populations. More than 98% of the Sf9 cells were viable and the
      culture consisted of diploid ( approximately 30%), tetraploid ( approximately
      60%), polyploidic (<10%) and apoptotic (<5%) cells. Treatment with the reference
      substances blasticidin, colchicine, paclitaxel, and cytochalasin D induced
      changes in ploidy and vitality, which were characteristic for the respective
      bioactive substance. Furthermore, crude extracts from the chivosazole producing
      Myxobacterium Sorangium cellulosum So ce56 induced an increase of polyploid cells
      and a decrease in total cell count, while a mutant producing nearly no
      chivosazole triggered none of these effects. Purified chivosazole induced the
      same effects as the wild type extract. Similar effects have been observed for the
      reference compound cytochalasin D. On the basis of this assay, crude extracts of
      ten different Myxobacteria cultures were screened. Three extracts exhibited
      strong cytotoxic activities, further five extracts induced weak changes in the
      ploidy distribution, and two extracts showed no detectable effect within the
      assay. Therefore, this robust assay provides the ability to discover and
      characterise cytotoxic and cytostatic bioactivities in crude bacterial extracts.

PMID- 19111839
TI  - Pathological, immunohistochemical and bacteriological study of tissues and milk
      of cows and fetuses experimentally infected with Brucella abortus.
AB  - This report describes a pathological, immunohistochemical and bacteriological
      study of 42 cows and their progeny (aborted fetuses, weak premature calves, and
      healthy full-term calves) infected at 6-7 months of gestation by conjunctival
      inoculation with Brucella abortus. Samples were collected at necropsy within 48 h
      of abortion or parturition. The most significant lesions were necrotizing and
      suppurative placentitis and lymphohistiocytic mastitis in cows, and fibrinous
      pleuritis, fibrinous pericarditis and bronchopneumonia in aborted fetuses. B.
      abortus was isolated more frequently from milk samples than from mammary tissues,
      and milk samples from cows with mastitis were often infected. Organisms were
      often demonstrated immunohistochemically and by culture in tissues showing
      moderate to severe histological changes.

PMID- 19111840
TI  - Comparative pathological study of the murine brain after experimental infection
      with classical rabies virus and European bat lyssaviruses.
AB  - European bat lyssaviruses (EBLVs) types 1 (EBLV-1) and 2 (EBLV-2) cause rabies in
      terrestrial species, but the pathological changes associated with neuroinvasion
      have yet to be fully elucidated. Swiss OF-1 mice were inoculated peripherally
      with strain RV61 (classical rabies virus), RV1423 (EBLV-1) or RV1332 (EBLV-2) to
      compare the nature and extent of histopathological changes produced. Inoculated
      animals developed varying degrees of non-suppurative encephalitis, and lyssavirus
      infection was confirmed by the detection of viral antigen. The lesions produced,
      which included perivascular cuffs and gliosis, were more severe after RV1423 or
      RV1332 infection than after RV61 infection. Perivascular cuffs were mainly
      localized to caudal brain regions, irrespective of the infecting strain; after
      RV1332 infection, however, they were particularly abundant, being composed of
      large numbers of inflammatory cells. T cells were the predominant lymphocytic
      component of the inflammatory infiltrate in both the Virchow-Robin space and the
      brain parenchyma. Viral antigen, which was widespread throughout the brain, was
      apparently unrelated to the degree of cuffing. The study suggested that there was
      increased immune activation after inoculation with strain RV1423 or RV1332,
      particularly the latter, but that this did not affect the final outcome.

PMID- 19111841
TI  - Functions of the breast cancer resistance protein (BCRP/ABCG2) in chemotherapy.
AB  - The breast cancer resistance protein, BCRP/ABCG2, is a half-molecule ATP-binding
      cassette transporter that facilitates the efflux of various anticancer agents
      from the cell, including 7-ethyl-10-hydroxycamptothecin, topotecan and
      mitoxantrone. The expression of BCRP can thus confer a multidrug resistance
      phenotype in cancer cells, and its transporter activity is involved in the in
      vivo efficacy of chemotherapeutic agents. Thus, the elucidation of the substrate
      preferences and structural relationships of BCRP is essential to understanding
      its in vivo functions during chemotherapeutic treatments. Single nucleotide
      polymorphisms (SNPs) have also been found to be key factors in determining the
      efficacy of chemotherapeutics, and those therapeutics that inhibit BCRP activity,
      such as the SNP that results in a C421A mutant, may result in unexpected side
      effects of the BCRP- anticancer drugs interaction even at normal dosages. In
      order to modulate the BCRP activity during chemotherapy, various compounds have
      been tested as inhibitors of this protein. Estrogenic compounds including
      estrone, several tamoxifen derivatives in addition to phytoestrogens and
      flavonoids have been shown to reverse BCRP-mediated drug resistance.
      Intriguingly, recently developed molecular targeted cancer drugs, such as the
      tyrosine kinase inhibitors imatinib mesylate, gefitinib and others, can also
      interact with BCRP. Since both functional SNPs and inhibitory agents of BCRP
      modulate the in vivo pharmacokinetics and pharmacodynamics of its substrate
      drugs, BCRP activity is an important consideration in the development of
      molecular targeted chemotherapeutics.

PMID- 19111842
TI  - Quality control of human ABCG2 protein in the endoplasmic reticulum:
      ubiquitination and proteasomal degradation.
AB  - Human ATP-binding cassette (ABC) transporter ABCG2 (BCRP/MXR/ABCP) is a plasma
      membrane protein carrying intra- and inter-molecular disulfide bonds and an N
      linked glycan. Both disulfide bond formation and N-glycosylation are critical
      check points determining the stability and degradation fate of ABCG2 protein in
      the endoplasmic reticulum (ER). Misfolded ABCG2 protein without those post
      translational modifications is removed from the ER by retrotranslocation to the
      cytosol compartment, ubiquitination by ubiquitin ligase, and finally degradation
      by proteasomes. Certain non-synonymous SNP variants of ABCG2 undergo such ER
      associated degradation (ERAD).

PMID- 19111843
TI  - Floating nuclear power plants: potential implications for radioactive pollution
      of the northern marine environment.
AB  - Recent media reports as to the development, construction and possible deployment
      of floating nuclear power plants in the northern regions has generated
      significant interest in the matter. This paper presents background to the concept
      of floating nuclear power plants, information as to possible designs and
      iterations and some aspects of potential concern with respect to safety and the
      potential for environmental or other impacts as a result of the development and
      use of such systems in the northern regions.

PMID- 19111844
TI  - Occurrence and distribution of hydrocarbons in surface sediments from Marseille
      Bay (France).

PMID- 19111845
TI  - A peptide fragment derived from the T-cell antigen receptor protein alpha-chain
      adopts beta-sheet structure and shows potent antimicrobial activity.
AB  - A 9-residue peptide, CP-1 (GLRILLLKV-NH(2)), is synthesized by solid-phase
      synthesis method. CP-1 is a C-terminal amidated derivative of a hydrophobic
      transmembrane segment (CP) of the T-cell antigen receptor (TCR) alpha-chain. CP-1
      shows broad-spectrum antimicrobial activities against Gram-positive and Gram
      negative bacteria with the minimal inhibitory concentration (MIC) values between
      3 and 77microM. Circular dichroism (CD) spectral data shows that CP-1 adopts a
      well-defined beta-sheet structure in membrane-mimicking environments. CP-1 kills
      E. coli without lysing the cell membrane or forming transmembrane pores. However,
      CP-1 can penetrate the bacterial cell membranes and accumulate in the cytoplasm
      in both Gram-positive S. aureus and Gram-negative E. coli. Moreover CP-1 shows
      binding affinity for plasmid DNA. These results indicate that the killing
      mechanism of CP-1 likely involves the penetration into the cytoplasm and binding
      to intracellular components such as DNA.

PMID- 19111847
TI  - Staff assignment practices in nursing homes: review of the literature.
AB  - Consistent assignment, whereby nursing home staff members, particularly certified
      nurse aides, are assigned to the same residents on most shifts, is increasingly
      viewed as a cornerstone of culture change in nursing homes. It has been advocated
      as a best-care model that increases residents' quality of life while contributing
      to a more stable frontline staff. Given these potential benefits, consistent
      assignment is now widely viewed as superior to rotating assignment, an
      alternative staffing model that aims to distribute care burden more fairly among
      staff and ensure that workers are familiar with most residents. Despite favorable
      anecdotal reports about the benefits of consistent assignment, the research
      literature reports mixed and sometimes contradictory findings for this staffing
      practice. This article reviews the research pertaining to staff assignment
      practices in nursing homes. Reviewed here are 13 reports on experimental trials
      (6 reports), evaluation research (4 reports), and nursing home surveys (3
      reports). The review reveals broad diversity in staffing practices and raises
      questions that challenge popular assumptions about consistent assignment. The
      article closes with a discussion of the research, policy, and practice
      implications of the research findings.

PMID- 19111846
TI  - Cardiovascular disease care in the nursing home: the need for better evidence for
      outcomes of care and better quality for processes of care.

PMID- 19111848
TI  - Certified nursing assistants' perceptions of nursing home patient safety culture:
      is there a relationship to clinical outcomes?
AB  - OBJECTIVES: The main objective of this study was to examine whether certified
      nursing assistants' (CNAs') perceptions of patient safety culture (PSC) were
      correlated with clinical outcomes (rates of falls, pressure ulcers, and daily
      restraint use) in a random sample of nursing homes. An additional objective was
      to describe facility-level and CNA-level characteristics that were associated
      with CNA PSC scores. DESIGN: We conducted a secondary data analysis using data
      that adapted the Hospital Survey of Patient Safety Culture (HSOPSC) for nursing
      homes. The HSOPSC data were merged with data from the Minimum Data Set (MDS),
      Online Survey Certification and Reporting (OSCAR) system, and Area Resource File
      (ARF). PARTICIPANTS AND SETTING: CNAs from a random sample of 72 nursing homes in
      5 randomly selected states during the first 2 quarters of 2005. MEASUREMENTS: The
      relationships between clinical outcomes and CNA PSC scores were evaluated. The
      relationships between CNA PSC and facility characteristics, such as profit status
      and bed occupancy, and CNA characteristics such as education and tenure were also
      assessed. Data were analyzed using Poisson, multinomial logistic, and linear
      regression, and generalized estimating equations (GEE); descriptive statistics
      were compiled for demographic data. RESULTS: Of 2872 CNAs, 1579 completed the
      survey, for a 55% response rate. Results of regression analyses suggest that
      higher (more developed and more desirable) CNA PSC scores were associated with
      increased reporting of falls (B = 0.015; P = .000). Facilities with higher total
      CNA PSC scores were more likely to report moderate restraint use, whereas
      facilities with lower CNA PSC scores were more likely to report high restraint
      use (B = 0.172; P = .017). CNA PSC scores were not associated with differences in
      pressure ulcer rates. CONCLUSIONS: This study represents an important step in the
      evaluation of CNA PSC in nursing homes and shows that a relationship exists
      between PSC and selected clinical outcomes. Future work on nursing home PSC and
      additional clinical as well as workforce outcomes is indicated.

PMID- 19111850
TI  - Assessing the quality of evidence from randomized, controlled drug and
      nutritional supplement trials conducted among nursing home residents between 1968
      and 2004: what can we learn?
AB  - BACKGROUND: An estimated 1.5 million residents of nursing homes (NH) in the
      United States were prescribed an average of 7 to 8 medications each month.
      However, it is unknown which of these prescribed drugs and nutritional
      supplements have been tested for use among NH residents who often have distinct
      and complex needs compared with other geriatric patients. This pilot study
      addresses the quantity and quality of randomized, controlled drug and nutritional
      supplement trials that have been conducted among NH residents. METHOD: Using
      multiple search strategies and review protocol, I assessed the quality of
      evidence from randomized, controlled drug and nutritional supplement trials that
      had a parallel-group design, were conducted among NH residents, and were
      published in English between 1968 and October 2004. Internal validity of the
      trials was examined by assessing adequately reporting power calculation, drop
      outs (completion fraction), randomization and allocation concealment, blind
      status, and intention-to-treat analysis. External validity of the trials was
      examined by assessing adequately reporting the sample description, the inclusion
      and exclusion criteria, the recruitment process, and comorbidities and harm.
      RESULT: Relatively few drug and nutritional supplements have been tested among NH
      residents by well-designed and executed randomized controlled trials (N = 42).
      The total number of participants (N = 7941) is small. The quality of many trials
      is poor. CONCLUSIONS: Given the limited number and poor quality of existing
      trials conducted among NH residents in this pilot study, I conclude that there is
      a limited body of evidence that could be used to establish quality of care
      standards or pay for performance criteria for drug therapy and nutritional
      supplements in NH. Long-term care providers face a great challenge in practicing
      evidence-based medicine in prescribing drugs and nutritional supplements.

PMID- 19111849
TI  - A randomized, double-blind, placebo-controlled tolerability study of
      intramuscular aripiprazole in acutely agitated patients with Alzheimer's,
      vascular, or mixed dementia.
AB  - OBJECTIVES: To evaluate the tolerability of intramuscular (IM) aripiprazole in
      patients with agitation associated with dementia. DESIGN: A 24-hour, double
      blind, placebo-controlled, randomized study. SETTING: Sixteen healthcare
      facilities in the United States. PARTICIPANTS: A total of 129 patients with acute
      agitation associated with Alzheimer's, vascular or mixed dementia in healthcare
      facilities. INTERVENTION: Patients were randomized to IM aripiprazole (5 mg, 10
      mg, or 15 mg) or IM placebo administered in divided doses 2 hours apart.
      MEASUREMENTS: Safety assessments included adverse event (AE) reporting, vital
      signs, and electrocardiograms. Preliminary efficacy analyses used the Positive
      and Negative Syndrome Scale-Excited Component (PEC) scores and Agitation-Calmness
      Evaluation Scale (ACES). RESULTS: There was greater incidence of AEs with IM
      aripiprazole (50% to 60%) than IM placebo (32.0%), but over 90% were mild or
      moderate in severity. The incidence of oversedation was low. PEC scores showed
      greater improvements in agitation with IM aripiprazole 10 mg and 15 mg compared
      with IM placebo. CONCLUSION: A total of 10 mg or 15 mg of IM aripiprazole
      administered in divided doses was safe and well tolerated for treatment of
      agitation associated with Alzheimer's, vascular, or mixed dementia in long-term
      care. Preliminary analysis showed greater efficacy compared with IM placebo.

PMID- 19111851
TI  - Characteristics of nursing home social services directors: how common is a degree
      in social work?
AB  - PURPOSE: To report the percentage of nursing homes whose social services director
      has a degree in social work, to report the characteristics of social service
      directors, and to describe the characteristics of nursing homes most likely to
      employ a degreed social worker. These questions are important because social
      workers are core members of the interdisciplinary team in nursing homes and have
      responsibilities for the psychosocial well-being of residents. DESIGN AND
      METHODS: Cross-sectional nationally representative survey of 1071 social service
      directors employed in US nursing homes certified to receive Medicare and/or
      Medicaid. RESULTS: Most nursing homes do employ at least one (and typically only
      one) social service staff person. Most are employed full-time and half have a
      degree in social work. About 20% do not have a college degree. The vast majority
      of social service directors are white and are women. Close to 40% are licensed
      social workers. Full-time salaries varies enormously from less than $15,000 to
      over $60,000 per year. Most do not belong to an organization that helps them keep
      apprised of developments in nursing home social services. Using logistic
      regression and controlling for the effects of other independent variables, for
      profit nursing homes with fewer than 121 beds, in sparsely populated counties in
      the West are the least likely to hire a degreed social worker as social service
      director. IMPLICATIONS: The wide range in educational preparedness and salary
      indicates 2 roles: a social work role and a social services role. The different
      roles have implications for initial role preparation and continuing education.
      Clear communication about the role expectations associated with social services
      and social work would benefit residents, family, staff, and physicians, who would
      then be better prepared to draw on their skills in helping to meet the
      psychosocial needs of residents.

PMID- 19111852
TI  - Assessment of visual function in institutionalized elderly patients.
AB  - OBJECTIVE: To describe the visual function and ocular health of frail elderly
      patients institutionalized in a tertiary care university-affiliated geriatric
      hospital. DESIGN: Retrospective file review. SETTING: A university-affiliated
      geriatric hospital. PARTICIPANTS: 440 patient files. MEASUREMENTS: The archived
      clinical files of patients from the long-term care beds of the Institut
      universitaire de geriatrie de Montreal, who had died between April 2000 and 2004
      were reviewed. Pertinent medical and visual characteristics were extracted and
      entered into a database for analysis. RESULTS: The age of the patients ranged
      from 65 to 104 years. The major ocular conditions observed were cataract,
      pseudophakia, conjunctivitis-blepharitis, age-related macular degeneration, and
      glaucoma. Of the 231 patients referred for a partial or full eye examination,
      visual acuity was available in 178. Visual impairment was considered absent in 87
      patients; mild in 52; moderate in 17; and 22 patients were legally blind. Of the
      105 patients referred for a full eye examination, an evaluation of the
      refraction, visual acuity, and ocular health was possible in 89, irrespective of
      their cognitive status. CONCLUSION: These data demonstrate that the vast majority
      of severely disabled elderly patients examined retained good visual acuity into
      advanced age. The most prevalent ocular conditions observed are treatable,
      thereby emphasizing the importance of regular eye care for the institutionalized
      frail elderly. The results clearly demonstrate that it is possible to perform a
      complete evaluation of visual function and ocular health in the elderly
      institutionalized patient, independent of age, cognitive status, or communication
      disorders.

PMID- 19111853
TI  - Educating nursing home staff about the progression of dementia and the comfort
      care option: impact on family satisfaction with end-of-life care.
AB  - OBJECTIVE: There is a growing consensus on the relevance of a palliative care
      approach in end-stage dementia. The objective of this study was to assess the
      impact, in terms of family satisfaction with end-of-life care, of a nursing home
      (NH) pilot educational program for nursing staff and physicians on comfort care
      and advanced dementia. METHODS: The intervention, implemented in one voluntary
      NH, consisted of an educational program that included providing an information
      booklet to all NH staff, and optionally to families. Satisfaction with care was
      compared using a validated instrument, the "After death bereaved family member
      interview" pre- and post-intervention. Pre and post groups were composed of close
      relatives of residents who died in the context of advanced dementia. RESULTS:
      Twenty-seven contact persons were interviewed pre-intervention and 21 post
      intervention (participation rate of 60% for both groups). Descriptive statistics
      showed better scores on satisfaction with pain control, emotional support,
      treating patient with respect, and information on what to expect while patient
      was dying, in the post-intervention group. Comparison of overall scale scores
      revealed no statistical differences between the 2 groups, although the post
      intervention group expressed greater satisfaction in the area of communication
      with the health care team (8.0 versus 6.6, P = .109) and greater global
      satisfaction with care (8.3 versus 7.3, P = .087). DISCUSSION: Although not
      significant, results as to the effectiveness of such an intervention to improve
      family satisfaction with end-of-life care are encouraging. CONCLUSION: The
      booklet, as support tool, and the educational program may have facilitated
      communication within the team, and between the team and family members.
      Replication of this intervention in a multicenter NH population is needed to
      adequately assess its effectiveness.

PMID- 19111854
TI  - Acute myocardial infarction in nursing home residents: adherence to treatment
      guidelines reduces mortality, but why is adherence so low?
AB  - OBJECTIVES: To investigate the applicability of clinical practice guidelines
      (CPGs) to the care of nursing home (NH) residents who experience acute myocardial
      infarction (AMI). DESIGN: Secondary examination of data from the national
      Cooperative Cardiovascular Project. SETTING: 6684 US hospitals. PARTICIPANTS: A
      NH-dwelling (N = 8151) cohort and a community-dwelling cohort (N = 119,012).
      MEASUREMENTS: Adherence to AMI guidelines and associated mortality rates.
      RESULTS: Mortality at 30 days and 1 year respectively was 39.5% and 65.4% in the
      NH cohort versus 17.5% and 31.1% in the community-dwelling cohort (P < .001).
      Among patients who were ideally eligible to receive aspirin, 58.8% of the NH
      cohort and 78.9% of the community-dwelling cohort actually received aspirin (P <
      .001). Among patients who were ideally eligible for beta-blockers, 43.8% of the
      NH cohort and 61.4% of the community-dwelling cohort received beta-blockers (P <
      .001). The 30-day mortality for NH patients who were ideally eligible for aspirin
      but did not receive aspirin was significantly higher compared with NH patients
      who were ideally eligible but did receive aspirin (49.2% versus 26.0%, P < .001).
      Similarly, mortality was significantly higher for NH patients who were ideally
      eligible for beta-blockers but did not receive a beta-blocker (35.3% versus
      18.6%, P < .001). CONCLUSION: Only half of NH patients who are ideally eligible
      for aspirin and beta-blockers received these medications, yet mortality was
      significantly lower in patients who were treated with these medications. These
      results demonstrate the effect of applying AMI guidelines to NH patients while
      also raising the question of what factors guided decisions not to provide these
      medications.

PMID- 19111855
TI  - Oropharyngeal dysphagia assessment and treatment efficacy: setting the record
      straight (response to Campbell-Taylor).
AB  - In September 2008, an article was published in the Journal of the American
      Medical Directors Association criticizing current dysphagia assessment and
      management practices performed by speech-language pathologists in Long-Term Care
      (LTC) settings. In the same issue, an editorial invited dialogue on the points
      raised by Campbell-Taylor. We are responding to this call for dialogue. We find
      Campbell-Taylor's interpretation of the literature to be incomplete and one
      sided, leading to misleading and pessimistic conclusions. We offer a
      complementary perspective to balance this discussion on the 4 specific questions
      raised: (1) Is the use of videofluoroscopy warranted for evaluating dysphagia in
      the LTC population? (2) How effective are thickened liquids and other
      interventions for preventing aspiration and do they contribute to reduction of
      morbidity? (3) Can aspiration be prevented and is its prevention important? and
      (4) Is there sufficient evidence to justify dysphagia intervention by speech
      language pathologists?

PMID- 19111856
TI  - Implementing a pain management program in a long-term care facility using a
      quality improvement approach.
AB  - BACKGROUND: Pain constitutes a constant challenge facing staff and residents of
      skilled nursing facilities (SNF) and nursing homes (NH). Many SNF and NH have not
      adopted a uniform plan to assess and treat pain for their residents despite
      published literature that demonstrates that the implementation of scales improves
      detection and treatment of pain. The objective of this study was to analyze the
      baseline pain level in the institutionalized elderly, and then implement a
      standard pain scale for its assessment and evaluation, while simultaneously
      identifying challenges in adopting this standardized method. METHODS: As part of
      a Quality Improvement Project (QI), a total of 40 patients were chosen at random
      in 2 of the major skilled care and dementia units at a Columbia area nursing
      home, 20 patients from each. A chart review was conducted to document the
      presence or absence of pain syndromes, pain medications used, and use of
      standardized tools for the evaluation of pain. Documentation regarding diagnosis
      of depression and behavioral problems were also noted as potential markers for
      the manifestation of pain. Verbal and nonverbal pain scales were introduced and
      approved by the medical and nursing staff. Training sessions for the
      administration of such tools were implemented. A baseline evaluation of pain
      level was obtained applying these newly adopted tools. One cycle using the PDSA
      (Plan-Do-Study and Act) model for QI was followed. RESULTS: Our evaluation showed
      that 84.2% (32/38) of our study population were females, and the mean age was
      91.4 years. Fifty percent (19/38) of patients had mild to moderate pain. Because
      of nonstandardized approaches to analgesia, some regimens rendered clear
      potential for toxicity: ie, receiving more than 3 grams per day of acetaminophen.
      Most patients with cognitive deficits had lower levels of moderate pain (9.5%
      [2/21]) but higher levels of mild pain (33.3% [7/21]) when compared with patients
      with normal cognition or mild cognitive deficits (35.3% [6/17] and 17.6% [3/17],
      respectively). Nursing staff adopted successfully the chosen pain tools and gave
      positive feedback after the trial period, indicating that they were helpful tools
      to identify pain and treat it promptly. Active participation of nursing staff
      through the process of decision making, tailoring of the pain assessment scales,
      and feedback during the period of implementation of pain assessment tools was
      perceived to facilitate better results. New cycles of pain evaluation and
      improvement were scheduled. CONCLUSIONS: Pain evaluation and management is of
      paramount importance because of its high prevalence and demonstrated deleterious
      effects on both quality of life and long-term survival. Tools for verbal and
      nonverbal evaluation of pain are necessary in both NH and SCF. Also, regular
      cognitive and behavioral assessment may help evaluate pain by providing
      additional information to physicians, nurses, and other caregivers when treatment
      becomes more challenging and complex. The use of standard standing orders can
      easily help decrease the potential of toxicity related to the use of analgesics.

PMID- 19111857
TI  - A part-time geriatrician's experience: a balancing act.

PMID- 19111858
TI  - The use of hypodermoclysis without hyaluronidase.

PMID- 19111860
TI  - Lessons learned from Hurricane Gustav--the second time around.

PMID- 19111861
TI  - Nightmares and memantine: a case report and review of literature.

PMID- 19111863
TI  - Oropharyngeal dysphagia in long-term care: response from ASHA.

PMID- 19111866
TI  - Hospitalization in veterans residing in Veterans Health Administration nursing
      homes.

PMID- 19111869
TI  - A new blood-brain barrier model using primary rat brain endothelial cells,
      pericytes and astrocytes.
AB  - Blood-brain barrier (BBB) characteristics are induced and maintained by cross
      talk between brain microvessel endothelial cells and neighbouring elements of the
      neurovascular unit. While pericytes are the cells situated closest to brain
      endothelial cells morphologically and share a common basement membrane, they have
      not been used in co-culture BBB models for testing drug permeability. We have
      developed and characterized a new syngeneic BBB model using primary cultures of
      the three main cell types of cerebral microvessels. The co-culture of endothelial
      cells, pericytes and astrocytes mimick the anatomical situation in vivo. In the
      presence of both pericytes and astrocytes rat brain endothelial cells expressed
      enhanced levels of tight junction (TJ) proteins occludin, claudin-5 and ZO-1 with
      a typical localization at the cell borders. Further morphological evidence of the
      presence of interendothelial TJs was provided by electron microscopy. The
      transendothelial electrical resistance (TEER) of brain endothelial monolayers in
      triple co-culture, indicating the tightness of TJs reached 400Omegacm(2) on
      average, while the endothelial permeability coefficients (P(e)) for fluorescein
      was in the range of 3x10(-6)cm/s. Brain endothelial cells in the new model
      expressed glucose transporter-1, efflux transporters P-glycoprotein and multidrug
      resistance protein-1, and showed a polarized transport of rhodamine 123, a ligand
      for P-glycoprotein. To further characterize the model, drug permeability assays
      were performed using a set of 19 compounds with known in vivo BBB permeability.
      Good correlation (R(2)=0.89) was found between in vitroP(e) values obtained from
      measurements on the BBB model and in vivo BBB permeability data. The new BBB
      model, which is the first model to incorporate pericytes in a triple co-culture
      setting, can be a useful tool for research on BBB physiology and pathology and to
      test candidate compounds for centrally acting drugs.

PMID- 19111870
TI  - Catalpol attenuates nitric oxide increase via ERK signaling pathways induced by
      rotenone in mesencephalic neurons.
AB  - Catalpol has been shown to rescue neurons from kinds of damage in vitro and in
      vivo in previous reports. However, the effect of catalpol on the nitric oxide
      (NO) system via MAPKs signaling pathway of mesencephalic neurons largely remains
      to be verified. The current study examined that whether catalpol modulated NO and
      iNOS increase by rotenone in primary mesencephalic neurons and investigated its
      underlying signaling pathways. Present results indicated that catalpol inhibited
      primary mesencephalic neurons from apoptosis by morphological assay,
      immunocytochemistry and flow cytometric evaluation. Moreover, the ERK signaling
      pathway plays an important role in NO-mediated degeneration of neuron. The
      current results suggest that catalpol is a potential agent for the prevention of
      neurons apoptosis by regulating NO and iNOS increase in ERK-mediated
      neurodegenerative disorders.

PMID- 19111871
TI  - Early clinical features of dengue infection in Puerto Rico.
AB  - Early diagnosis of dengue is challenging because the initial symptoms are often
      non-specific, viraemia may be below detectable levels and serological tests
      confirm dengue late in the course of illness. Identifying dengue early in the
      clinical course could be useful in reducing dengue virus transmission in a
      community. This study analyzed data from 145 laboratory-positive and 293
      laboratory-negative dengue cases in Puerto Rico to define the early clinical
      features of dengue infection in children and adults and to identify the clinical
      features that predict a laboratory-positive dengue infection. Among children,
      rash and age were independently associated with laboratory-positive dengue
      infection. Rash in the absence of cough had a positive predictive value of 100%
      and a negative predictive value of 82.4% as a paediatric dengue screen. Among
      adults, eye pain, diarrhoea and absence of upper respiratory symptoms were
      independently associated with laboratory-positive dengue infection. No useful
      early predictors of dengue infection among adults were found. Using clinical
      features may promote earlier identification of a subset of paediatric dengue
      patients in Puerto Rico. Laboratory confirmation is still necessary for the
      accurate diagnosis of dengue infection.

PMID- 19111872
TI  - Proceedings of a joint meeting between the Norwegian Society of Infectious
      Diseases and the Royal Society of Tropical Medicine and Hygiene, Oslo, 20 June
      2008.
AB  - This paper presents the proceedings of a scientific meeting that was held between
      the Royal Society of Tropical Medicine and Hygiene and the Norwegian Infectious
      Diseases Society at Ulleval University Hospital, Oslo on 20 June 2008. Seven
      speakers updated the audience on recent advances in relevant issues, including
      international maternal and child health, podoconiosis, schistosomiasis and HIV,
      leprosy in the UK, rapid diagnostic tests for malaria, delayed diagnosis of
      tuberculosis and the Global Filariasis Programme. The meeting ended with a series
      of case presentations.

PMID- 19111868
TI  - Endothelin receptors and pain.
AB  - The endogenous endothelin (ET) peptides participate in a remarkable variety of
      pain-relatedprocesses. Pain that is elevated by inflammation, by skin incision,
      by cancer, during a Sickle Cell Disease crisis and by treatments that mimic
      neuropathic and inflammatory pain and are all reduced by local administration of
      antagonists of endothelin receptors. Many effects of endogenously released
      endothelin are simulated by acute, local subcutaneous administration of
      endothelin, which at very high concentrations causes pain and at lower
      concentrations sensitizes the nocifensive reactions to mechanical, thermal and
      chemical stimuli. PERSPECTIVE: In this paper we review the biochemistry, second
      messenger pathways and hetero-receptor coupling that are activated by ET
      receptors, the cellular physiological responses to ET receptor activation, and
      the contribution to pain of such mechanisms occurring in the periphery and the
      CNS. Our goal is to frame the subject of endothelin and pain for a broad
      readership, and to present the generally accepted as well as the disputed
      concepts, including important unanswered questions.

PMID- 19111873
TI  - The metastasis problem gets stickier.
AB  - The enormity and complexity of cancer genome data present significant challenges
      in downstream validation of novel oncogenes and tumor suppressors. In this issue
      of Cancer Cell, Hu et al. evaluate candidate oncogenes in a recurrent
      amplification in poor-prognosis breast cancers. They identify and validate the
      prometastatic gene metadherin (MTDH) as a key modulator of endothelial adhesion
      and chemoresistance.

PMID- 19111874
TI  - Tumor-associated fibroblasts as "Trojan Horse" mediators of resistance to anti
      VEGF therapy.
AB  - While targeting VEGF has shown success against a number of human cancers, drug
      resistance has resulted in compromised clinical benefits. In this issue of Cancer
      Cell, Crawford et al. (2009) report that tumors resistant to anti-VEGF therapy
      stimulate tumor-associated fibroblasts to express proangiogenic PDGF-C,
      implicating it as a potential therapeutic target.

PMID- 19111875
TI  - Unholy matrimony: Aurora A and N-Myc as malignant partners in neuroblastoma.
AB  - Aurora A is a mitotic kinase that is essential for regulation of the G2/M
      checkpoint. In this issue of Cancer Cell, Otto et al. report that Aurora A
      interacts with MYCN, a potent oncogene in human neuroblastoma, and sequesters it
      from proteolytic degradation. This surprising finding further enhances Aurora A's
      potential as a therapeutic target.

PMID- 19111876
TI  - Curing APL: differentiation or destruction?
AB  - In a recent issue of Nature Medicine, Nasr et al. show that the effectiveness of
      all-trans retinoic acid and arsenic trioxide in acute promyelocytic leukemia is
      independent of their ability to cause differentiation. Targeted destruction of
      the PML-RARalpha oncoprotein appears key to eliminating the cells from which
      relapse can arise.

PMID- 19111877
TI  - MTDH activation by 8q22 genomic gain promotes chemoresistance and metastasis of
      poor-prognosis breast cancer.
AB  - Targeted therapy for metastatic diseases relies on the identification of
      functionally important metastasis genes from a large number of random genetic
      alterations. Here we use a computational algorithm to map minimal recurrent
      genomic alterations associated with poor-prognosis breast cancer. 8q22 genomic
      gain was identified by this approach and validated in an extensive collection of
      breast tumor samples. Regional gain of 8q22 elevates expression of the metastasis
      gene metadherin (MTDH), which is overexpressed in more than 40% of breast cancers
      and is associated with poor clinical outcomes. Functional characterization of
      MTDH revealed its dual role in promoting metastatic seeding and enhancing
      chemoresistance. These findings establish MTDH as an important therapeutic target
      for simultaneously enhancing chemotherapy efficacy and reducing metastasis risk.

PMID- 19111878
TI  - PDGF-C mediates the angiogenic and tumorigenic properties of fibroblasts
      associated with tumors refractory to anti-VEGF treatment.
AB  - Tumor- or cancer-associated fibroblasts (TAFs or CAFs) from different tumors
      exhibit distinct angiogenic and tumorigenic properties. Unlike normal skin
      fibroblasts or TAFs from TIB6 tumors that are sensitive to anti-VEGF treatment
      (TAF-TIB6), TAFs from resistant EL4 tumors (TAF-EL4) can stimulate TIB6 tumor
      growth even when VEGF is inhibited. We show that platelet-derived growth factor C
      (PDGF-C) is upregulated in TAFs from resistant tumors. PDGF-C-neutralizing
      antibodies blocked the angiogenesis induced by such TAFs in vivo, slowed the
      growth of EL4 and admixture (TAF-EL4 + TIB6) tumors, and exhibited additive
      effects with anti-VEGF-A antibodies. Hence, our data reveal an additional
      mechanism for TAF-mediated tumorigenesis and suggest that some tumors may
      overcome inhibition of VEGF-mediated angiogenesis through upregulation of PDGF-C.

PMID- 19111879
TI  - Hypoxia-induced lysyl oxidase is a critical mediator of bone marrow cell
      recruitment to form the premetastatic niche.
AB  - Tumor cell metastasis is facilitated by "premetastatic niches" formed in
      destination organs by invading bone marrow-derived cells (BMDCs). Lysyl oxidase
      (LOX) is critical for premetastatic niche formation. LOX secreted by hypoxic
      breast tumor cells accumulates at premetastatic sites, crosslinks collagen IV in
      the basement membrane, and is essential for CD11b+ myeloid cell recruitment.
      CD11b+ cells adhere to crosslinked collagen IV and produce matrix
      metalloproteinase-2, which cleaves collagen, enhancing the invasion and
      recruitment of BMDCs and metastasizing tumor cells. LOX inhibition prevents
      CD11b+ cell recruitment and metastatic growth. CD11b+ cells and LOX also
      colocalize in biopsies of human metastases. Our findings demonstrate a critical
      role for LOX in premetastatic niche formation and support targeting LOX for the
      treatment and prevention of metastatic disease.

PMID- 19111880
TI  - Malignant astrocytomas originate from neural stem/progenitor cells in a somatic
      tumor suppressor mouse model.
AB  - Malignant astrocytomas are infiltrative and incurable brain tumors. Despite
      profound therapeutic implications, the identity of the cell (or cells) of origin
      has not been rigorously determined. We previously reported mouse models based on
      conditional inactivation of the human astrocytoma-relevant tumor suppressors p53,
      Nf1, and Pten, wherein through somatic loss of heterozygosity, mutant mice
      develop tumors with 100% penetrance. In the present study, we show that tumor
      suppressor inactivation in neural stem/progenitor cells is both necessary and
      sufficient to induce astrocytoma formation. We demonstrate in vivo that
      transformed cells and their progeny undergo infiltration and multilineage
      differentiation during tumorigenesis. Tumor suppressor heterozygous neural
      stem/progenitor cultures from presymptomatic mice show aberrant growth advantage
      and altered differentiation, thus identifying a pretumorigenic cell population.

PMID- 19111881
TI  - Genome-wide loss-of-function screen reveals an important role for the proteasome
      in HDAC inhibitor-induced apoptosis.
AB  - Aberrant acetylation has been strongly linked to tumorigenesis, and the
      modulation of acetylation through targeting histone deacetylases (HDACs) is
      gathering increasing pace as a viable therapeutic strategy. A genome-wide loss-of
      function screen identified HR23B, which shuttles ubiquitinated cargo proteins to
      the proteasome, as a sensitivity determinant for HDAC inhibitor-induced
      apoptosis. HR23B also governs tumor cell sensitivity to drugs that act directly
      on the proteasome. The level of HR23B influences the response of tumor cells to
      HDAC inhibitors, and HR23B is found at high levels in cutaneous T cell lymphoma
      in situ, a malignancy that responds favorably to HDAC inhibitor-based therapy.
      These results suggest that deregulated proteasome activity contributes to the
      anticancer activity of HDAC inhibitors.

PMID- 19111882
TI  - Stabilization of N-Myc is a critical function of Aurora A in human neuroblastoma.
AB  - In human neuroblastoma, amplification of the MYCN gene predicts poor prognosis
      and resistance to therapy. In a shRNA screen of genes that are highly expressed
      in MYCN-amplified tumors, we have identified AURKA as a gene that is required for
      the growth of MYCN-amplified neuroblastoma cells but largely dispensable for
      cells lacking amplified MYCN. Aurora A has a critical function in regulating
      turnover of the N-Myc protein. Degradation of N-Myc requires sequential
      phosphorylation by cyclin B/Cdk1 and Gsk3. N-Myc is therefore degraded during
      mitosis in response to low levels of PI3-kinase activity. Aurora A interacts with
      both N-Myc and the SCF(Fbxw7) ubiquitin ligase that ubiquitinates N-Myc and
      counteracts degradation of N-Myc, thereby uncoupling N-Myc stability from growth
      factor-dependent signals.

PMID- 19111883
TI  - Intranasal administration of the synthetic polypeptide from the C-terminus of the
      circumsporozoite protein of Plasmodium berghei with the modified heat-labile
      toxin of Escherichia coli (LTK63) induces a complete protection against malaria
      challenge.
AB  - Needle-free procedures are very attractive ways to deliver vaccines because they
      diminish the risk of contamination and may reduce local reactions, pain or pain
      fear especially in young children with a consequence of increasing the
      vaccination coverage for the whole population. For this purpose, the possible
      development of a mucosal malaria vaccine was investigated. Intranasal
      immunization was performed in BALB/c mice using a well-studied Plasmodium berghei
      model antigen derived from the circumsporozoite protein with the modified heat
      labile toxin of Escherichia coli (LTK63), which is devoid of any enzymatic
      activity compared to the wild type form. Here, we show that intranasal
      administration of the two compounds activates the T and B cell immune response
      locally and systemically. In addition, a total protection of mice is obtained
      upon a challenge with live sporozoites.

PMID- 19111884
TI  - Effects of leaves extract of Ocimum sanctum L. on arsenic-induced toxicity in
      Wistar albino rats.
AB  - Therapeutic efficacy of oral administration of Ocimum sanctum (200mg/kg, once
      daily) post arsenic exposure (100 ppm in drinking water for 4 months) was
      investigated in rats. Animals exposed to arsenic (III) showed a significant
      inhibition of delta-aminolevulinic acid dehydratase (ALAD) activity, decrease in
      reduced glutathione (GSH) level and an increase in reactive oxygen species (ROS)
      in blood. On the other hand, a significant decrease in hepatic ALAD, and increase
      in delta-aminolevulinic acid synthetase activity were noted after arsenic
      exposure. These changes were accompanied by an increase TBARS level in liver and
      kidney. Activities of liver, kidney and brain superoxide dismutase and catalase
      also showed a decrease on arsenic exposure. Administration of O. sanctum post
      arsenic exposure, exhibited significant recovery in blood ALAD activity while, it
      restored blood GSH and ROS levels. Other blood biochemical variables remained
      unchanged on O. sanctum supplementation. Interestingly, there was a marginal, but
      significant depletion of arsenic from blood, liver and kidneys. The results
      conclude that post arsenic administration of O. sanctum has significant role in
      protecting animals from arsenic-induced oxidative stress and in the depletion of
      arsenic concentration. Further studies thus can be recommended for determining
      the effect of co-administrating of O. sanctum during chelating therapy with a
      thiol chelator.

PMID- 19111885
TI  - Gonad plasticity and gametogenesis in the endangered Spanish toothcarp Aphanius
      iberus (Teleostei: Cyprinodontidae).
AB  - The Spanish toothcarp Aphanius iberus is an endangered species which inhabits
      small rivers, creeks, salt marshes and marine salt pans in the Mediterranean
      coast of Spain. No differences in weights were observed among females or males
      taken from different environments. Analyses of the morphology of the gonads and
      the gametogenesis were performed in fish taken from different environments by
      comparing gamete development in females and in males and gonadal cell
      proliferation in the testis. A high degree of plasticity was observed in the
      gonad morphology of A. iberus. Females possess two ovaries which show non
      restricted oogenesis with all germ cell stages within the same ovigerous
      lamellae, while males possess gonads without any clear division with the typical
      restricted pattern observed in cyprinodontid fish. Some females and males showed
      asymetrically developed gonads. Proliferation of germ cells in testis is located
      only in the periphery of the gonads corresponding with primary and secondary
      spermatogonia. Salinity did not influence gonad plasticity or the appearance of
      mature germ cells in either females or males. This is the first study to provide
      a microscopic description of oogenesis and spermatogenesis in A. iberus at
      extreme different environmental conditions.

PMID- 19111886
TI  - Imidazenil, a non-sedating anticonvulsant benzodiazepine, is more potent than
      diazepam in protecting against DFP-induced seizures and neuronal damage.
AB  - Organophosphate (OP)-nerve agent poisoning may lead to prolonged epileptiform
      seizure activity, which can result in irreversible neuronal brain damage. A
      timely and effective control of seizures with pharmacological agents can minimize
      the secondary and long-term neuropathology that may result from this damage.
      Diazepam, the current anticonvulsant of choice in the management of OP poisoning,
      is associated with unwanted effects such as sedation, amnesia, cardio-respiratory
      depression, anticonvulsant tolerance, and dependence liabilities. In search for
      an efficacious and safer anticonvulsant benzodiazepine, we studied imidazenil, a
      potent anticonvulsant that is devoid of sedative action and has a low intrinsic
      efficacy at alpha1- but is a high efficacy positive allosteric modulator at
      alpha5-containing GABA(A) receptors. We compared the potency of a combination of
      2 mg/kg, i.p. atropine with: (a) imidazenil 0.05-0.5 mg/kg i.p. or (b) equipotent
      anti-bicuculline doses of diazepam (0.5-5 mg/kg, i.p.), against diisopropyl
      fluorophosphate (DFP; 1.5 mg/kg, s.c.)-induced status epilepticus and its
      associated neuronal damage. The severity and frequency of seizure activities were
      determined by continuous radio telemetry recordings while the extent of neuronal
      damage and neuronal degeneration were assessed using the TUNEL-based cleaved DNA
      end-labeling technique or neuron-specific nuclear protein (NeuN)-immunolabeling
      and Fluoro-Jade B (FJB) staining, respectively. We report here that the
      combination of atropine and imidazenil is at least 10-fold more potent and longer
      lasting than the combination with diazepam at protecting rats from DFP-induced
      seizures and the associated neuronal damage or ongoing degeneration in the
      anterior cingulate cortex, CA1 hippocampus, and dentate gyrus. While 0.5 mg/kg
      imidazenil effectively attenuated DFP-induced neuronal damage and the ongoing
      neuronal degeneration in the anterior cingulate cortex, dentate gyrus, and CA1
      hippocampus, 5 mg/kg or a higher dose of diazepam is required to produce similar
      protective effects. These finding suggests that imidazenil, a non-sedating
      anticonvulsant BZ ligand, is a more potent, effective, and safer drug than
      diazepam in protecting rats from DFP-induced seizures and the associated neuronal
      damage and/or ongoing neuronal degeneration.

PMID- 19111887
TI  - Photodegradation product of sulcotrione and the physiological response of maize
      (Zea mays) and white mustard (Sinapis alba).
AB  - One of the strategies for decreasing the consumption of herbicides consists in
      improving their uptake and efficiency. It was suggested that the photodegradation
      of herbicides due to sunlight results in a greater demand of herbicides to be
      introduced into the environment in order to ensure the plant protection activity.
      Moreover, an ecotoxicological effect of the photoproducts needs to be clarified.
      The physiological response of Zea mays and Sinapis alba (weed) to sulcotrione and
      its main photoproduct, called chromone (xanthene-1,9-dione-3,4-dihydro-6
      methylsulfonyl), was evaluated under controlled conditions in a growth chamber.
      The dose-response effects were determined on Z. mays and S. alba. Using the
      sulcotrione (doses ranging from 1 to 9mg per plant), the physiological parameters
      indicated a decrease of photosynthesis for the S. alba species while the Z. mays
      species were only slightly affected. On the contrary, the chromone had no
      herbicide activity on both species. The sulcotrione is known to block 4
      hydroxyphenyl pyruvate dioxygenase (HPPD) enzyme. The differences between the
      parent herbicide and the photoproduct could be ascribed to drastic structural
      modifications. We have shown that the chromone probably do not block the HPPD
      active site.

PMID- 19111888
TI  - Kinetic and isotope analyses of tetrachloroethylene and trichloroethylene
      degradation by model Fe(II)-bearing minerals.
AB  - The kinetics and in some cases stable carbon isotope fractionation associated
      with abiotic reductive dechlorination of tetrachloroethylene (PCE) and
      trichloroethylene (TCE) by model Fe(II)-bearing minerals present in anaerobic
      soils were measured. The minerals studied were chloride green rust (GR-Cl),
      sulfate green rust (GR-SO(4)), pyrite, magnetite, and adsorbed Fe(II) or FeS
      formed at the surface of goethite by treatment with dissolved Fe(II) or S(-II).
      We observed some abiotic transformation of PCE and TCE in every system studied,
      as evidenced by the presence of abiotic reaction products. Bulk enrichment
      factors (epsilon(bulk) values) for TCE transformation by GR-Cl and pyrite were 
      23.0+/-1.8 per thousand and -21.7+/-1.0 per thousand, respectively, which are
      more negative than reported values for microbial TCE dechlorination and could
      provide one means for distinguishing microbial from abiotic dechlorination of TCE
      in the environment. Considering the time scale of subsurface remediation
      technologies, including natural attenuation, minerals such as green rusts,
      pyrite, and magnetite have the potential to contribute to the transformation of
      PCE and TCE at contaminated sites.

PMID- 19111889
TI  - Spatial character of polychlorinated biphenyls from soil and respirable
      particulate matter in Taiyuan, China.
AB  - As one of China's great metropolises, Taiyuan is affected by heavy chemical
      industry and manufacture of chemical products, and faces pollution from
      polychlorinated biphenyls (PCBs). Therefore, this study was conducted to
      determine the PCB concentrations in various environmental media in Taiyuan. We
      collected 15 soil samples, 34 respirable particulate matter (PM) samples (17 of
      PM(2.5) and 17 of PM(10)) from urban areas of Taiyuan, and measured a total of
      144 PCB congeners (including some coeluting PCB congeners). The total PCB
      concentrations were 51-4.7 x 10(3) pg g(-1) in soil, 27-1.4 x 10(2) pg m(-3) in
      PM(2.5) and 16-1.9 x 10(2) pg m(-3) in PM(10). Of the PCB homologues, the
      dominant PCBs detected in the various media were all tri-CBs. Soil was relatively
      the most polluted media. Furthermore, principal-component analysis revealed that
      the major PCB source in Taiyuan may be associated with the main commercial PCB
      through long-range transmission. Toxic equivalency (TEQ) concentrations (based on
      ten dioxin-like PCBs) ranged from N.D. to 5.9 x 10(-3) pg-WHO TEQ g(-1) in soil,
      2.0 x 10(-4)-3.4 x 10(-3)pg-WHO TEQ m(-3) and 1.0 x 10(-4)-1.2 x 10(-3) pg-WHO
      TEQ m(-3) in PM(2.5) and PM(10), respectively. In previous studies, PCBs were not
      a severe component of contaminant in Taiyuan; however, this study suggested there
      is a potential threat of human exposure to PCBs for residents of Taiyuan.

PMID- 19111890
TI  - A theoretical and experimental physicochemical study of sulfur species in the
      anoxic lagoon of Aitoliko-Greece.
AB  - The spatiotemporal changes of metals, inorganic ions and physiochemical
      parameters of Aitoliko lagoon, an anoxic wetland in Western Greece, were studied
      with special emphasis in sulfur species. Theoretical physicochemical modeling was
      performed for the sulfur speciation, based on experimental pH and redox potential
      data. Accordingly, the speciation of sulfur in the lagoon can be operationally
      divided in two domains: (a) for depths d = 0-10 m below the surface, the sulfur
      speciation can be described by equilibrium reactions between the aqueous species.
      (b) At depths d > 10 m a progressive decline for SO4(2-) concentration is
      observed between theory and experiment. At the lagoon-bottom an elevated
      concentration of 19+/-2 mM SO4(2-) was measured, which cannot be described by
      physicochemical equilibrium based on the pH, E(h), O2 concentrations measured in
      situ. Accordingly, we suggest that additional biogeochemical processes, such as
      sulfur bacteria activity, have to be invoked. Of particular importance is that
      the experimental pH-pe values cross the critical region where the interplay of
      SO4(2-)/S2(-)/H2S occurs. This explains why a relatively small fluctuation of pH,
      pe values may result in a shift of the equilibrium over one sulfur species. This
      explains the, otherwise accidental, previously reported releases of H2S in the
      air over the lagoon.

PMID- 19111891
TI  - Unnoticed regularity violation elicits change-related brain activity.
AB  - Event-related brain electric activity (ERP) was investigated to unnoticed visual
      changes. The orientation of grid elements (vertical or horizontal) changed after
      the presentation of 10-15 identical stimuli. The grid patterns were task
      irrelevant, and were presented in the background of a shape discrimination task.
      During the first half of the session, participants were unaware of the stimulus
      change. However, in comparison to the ERPs to the fifth identical stimuli,
      stimulus change elicited posterior negativities in the 270-375 ms range (visual
      mismatch negativity, vMMN). With participants instructed on the stimulus change,
      negativities emerged with earlier onset and with wider distribution. When
      stimulus change was preceded by only two identical stimuli, there were no such
      ERP effects. As the results show, a longer sequence of identical unattended
      stimuli may establish the memory representation of stimulus regularity, and
      violation of regularity is indicated by posterior negative ERP components (vMMN).

PMID- 19111892
TI  - Effect of time interval between prostaglandin F(2alpha) and GnRH treatments on
      occurrence of short estrous cycles in cyclic dairy heifers and cows.
AB  - Prostaglandin F(2alpha) (PGF(2alpha)) and GnRH treatments, when administered 24h
      apart during early diestrus, cause short estrous cycles in some dairy cows and
      heifers [J. Taponen, M. Kulcsar, T. Katila, L. Katai, G. Huszenicza, H. Rodriguez
      Martinez, Short estrous cycles and estrous signs after premature ovulations
      induced with cloprostenol and gonadotropin-releasing hormone in cyclic dairy
      cows, Theriogenology 2002; 58, 1291-1302]. We investigated the effect of a time
      interval between PGF(2alpha) and GnRH administration on the appearance of short
      cycles. Estrus was induced in heifers with dexcloprostenol. A second luteolysis
      was induced similarly on day 7 after ovulation, and either 0 (T0) or 24h (T24)
      later an injection of GnRH (0.1mg of gonadorelin) was administered. We monitored
      ovarian activity with progesterone analyses from blood plasma samples and with
      ultrasonography. Fourteen cases (12 in T0 and 2 in T24) were excluded due to
      either incomplete luteolysis (2 cases) or unresponsiveness to GnRH (10 in T0 and
      2 in T24). Short estrous cycles (7 to 8 d) were detected in 11/11 and 8/17
      heifers in groups T0 and T24, respectively, with a significant difference in the
      incidence of short cycles (P<0.01). In Experiment 2, estrus was induced in cows
      on day 8 (D8, n=18), 9 (D9, n=5), or 10 (D10, n=3) with cloprostenol and
      gonadorelin administered simultaneously. Daily milk samples were collected for
      progesterone analysis until subsequent estrus was detected and ovarian ultrasound
      examinations were performed. Eight cases had to be excluded due to
      unresponsiveness to GnRH, leaving 18 cases eligible for the study. Short estrous
      cycles (7-12d) were detected in 14/18 cows. In conclusion, shortening the time
      interval between PGF(2alpha) and GnRH treatments increased the incidence of short
      estrous cycles and appeared to increase the proportion of females unresponsive to
      GnRH treatment.

PMID- 19111893
TI  - Dynamics of prostate cancer stem cells with diffusion and organism response.
AB  - We develop a systems based model for prostate cancer, as a sub-system of the
      organism. We accomplish this in two stages. We first start with a general ODE
      that includes organism response terms. Then, to account for normally observed
      spatial diffusion of cell populations, the ODE is extended to a PDE that includes
      spatial terms. Numerical solutions of the full PDE are provided, and are
      indicative of traveling wave fronts. This motivates the use of a well known
      transformation to derive a canonically related (non-linear) system of ODEs for
      traveling wave solutions. For biological feasibility, we show that the non
      negative cone for the traveling wave system is time invariant. We also prove that
      the traveling waves have a unique global attractor. Biologically, the global
      attractor would be the limit for the avascular tumor growth. We conclude with
      comments on clinical implications of the model.

PMID- 19111894
TI  - The effect of 3-hydroxybutyrate methyl ester on learning and memory in mice.
AB  - Learning and memory requires energy-demanding cellular processes and can be
      enhanced when the brain is supplemented with metabolic substrates. In this study,
      we found that neuroglial cell metabolic activity was significantly elevated when
      cultured in the presence of polyhydroxybutyrate (PHB) degradation product 3
      hydroxybutyrate (3-HB) and derivatives. We demonstrated that the receptor for 3
      HB, namely, protein upregulated in macrophages by IFN-gamma (PUMA-G), was
      expressed in brain and upregulated in mice treated with 3-hydroxybutyrate methyl
      ester (3-HBME). We also affirmed increased expression of connexin 36 protein and
      phosphorylated ERK2 (extracellular signal-regulated kinase 2) in brain tissues
      following 3-HBME treatment, although these differences were not statistically
      significant. Mice treated with 3-HBME performed significantly (p<0.05) better in
      the Morris water maze than either the negative controls (no treatment) or
      positive controls (acetyl-l-carnitine treatment). Moreover, we found that 3-HBME
      enhanced gap junctional intercellular communication between neurons. Thus, 3-HB
      and derivatives enhance learning and memory, possibly through a signaling pathway
      requiring PUMA-G that increases protein synthesis and gap junctional
      intercellular communication.

PMID- 19111895
TI  - Infrared spectra of carbonate apatites: v2-Region bands.
AB  - The proportions of A and B carbonate ions in a selection of AB carbonate
      apatites, including hydroxyapatite (CHAP), chlorapatite (CCLAP) and fluorapatite
      (CFAP), have been obtained using the out-of-plane bend (nu(2)) bands of Fourier
      transform infrared (FTIR) spectra. Band area ratios (B/A) are in very good
      agreement with site occupancies from single-crystal X-ray structure refinement;
      the correlation is linear (1:1) for B/A values ranging up to three. Most
      compositions have nu(2) spectra with one band for A carbonate (at 878-880 cm(-1))
      and one for B (at 870-872 cm(-1)). Na-free AB CHAP has a third prominent band at
      862 cm(-1), which is assigned to the stuffed channel species (A2), and Na-bearing
      CFAP has a third band at 864 cm(-1), which is assigned to a second B carbonate
      environment (B2). The A2 and B2 assignments are based largely on spectral changes
      in annealed samples.

PMID- 19111896
TI  - In vitro and in vivo evaluation of the surface bioactivity of a calcium phosphate
      coated magnesium alloy.
AB  - Magnesium has shown potential application as a bio-absorbable biomaterial, such
      as for bone screws and plates. In order to improve the surface bioactivity, a
      calcium phosphate was coated on a magnesium alloy by a phosphating process (Ca-P
      coating). The surface characterization showed that a porous and netlike
      CaHPO(4).2H(2)O layer with small amounts of Mg(2+) and Zn(2+) was formed on the
      surface of the Mg alloy. Cells L929 showed significantly good adherence and
      significantly high growth rate and proliferation characteristics on the Ca-P
      coated magnesium alloy (p<0.05) in in-vitro cell experiments, demonstrating that
      the surface cytocompatibility of magnesium was significantly improved by the Ca-P
      coating. In vivo implantations of the Ca-P coated and the naked alloy rods were
      carried out to investigate the bone response at the early stage. Both routine
      pathological examination and immunohistochemical analysis demonstrated that the
      Ca-P coating provided magnesium with a significantly good surface bioactivity
      (p<0.05) and promoted early bone growth at the implant/bone interface. It was
      suggested that the Ca-P coating might be an effective method to improve the
      surface bioactivity of magnesium alloy.

PMID- 19111897
TI  - Characterization of type I collagen gels modified by glycation.
AB  - Chronic exposure to reducing sugars due to diabetes, aging, and diet can
      permanently modify extracellular matrix (ECM) proteins. This non-enzymatic
      glycosylation, or glycation, can lead to the formation of advanced glycation end
      products (AGE) and crosslinking of the ECM. This study investigates the effects
      of glycation on the properties of type I collagen gels. Incubation with glucose-6
      phopshate (G6P), a reducing sugar that exhibits similar but more rapid glycation
      than glucose, modified the biological and mechanical properties of collagen gels.
      Measures of AGE formation that correlate with increased complications in people
      with diabetes, including collagen autofluorescence, crosslinking, and resistance
      to proteolytic degradation, increased with G6P concentration. Rheology studies
      showed that AGE crosslinking increased the shear storage and loss moduli of type
      I collagen gels. Fibroblasts cultured on glycated collagen gels proliferated more
      rapidly than on unmodified gels, but glycated collagen decreased fibroblast
      invasion. These results show that incubation of type I collagen gels with G6P
      increases clinically relevant measures of AGE formation and that these changes
      altered cellular interactions. These gels could be used as in vitro models to
      study ECM changes that occur in diabetes and aging.

PMID- 19111898
TI  - The covalent attachment of adhesion molecules to silicone membranes for cell
      stretching applications.
AB  - Strain devices with expandable polydimethylsiloxane (PDMS) culture membranes are
      frequently used to stretch cells in vitro, mimicking mechanically dynamic tissue
      environments. To immobilize cell-adhesive molecules to the otherwise non-adhesive
      PDMS substrate, hydrophobic, electrostatic and covalent surface coating
      procedures have been developed. The efficacy of different coating strategies to
      transmit stretches to cells however is poorly documented and has not been
      compared. We describe a novel and simple procedure to covalently bind
      extracellular matrix proteins to the surface of stretchable PDMS membranes. The
      method comprises PDMS oxygenation, silanization, and covalent protein cross
      linking to the silane. We demonstrate improved attachment ( approximately 2
      fold), spreading ( approximately 2.5-fold) and proliferation ( approximately 1.2
      fold) of fibroblasts to our new coating over established coating procedures.
      Further, we compared the efficiency of different PDMS coating techniques to
      transmit stretches. After 15% stretch, the number of maximally (15 +/- 5%)
      stretched cells on our PDMS surface coating was approximately 7-fold higher
      compared with alternative coating protocols. Hence, covalent linkage of adhesive
      molecules is superior to non-covalent methods in providing a coating that resists
      large deformations and that fully transmit this stretch to cultured cells.

PMID- 19111899
TI  - Zebrafish 17beta-hydroxysteroid dehydrogenases: an evolutionary perspective.
AB  - The term 17beta-hydroxysteroid dehydrogenase (17beta-HSD) describes an enzyme
      that stereospecifically reduces or oxidizes a keto- or hydroxy group at C17 of
      the steroid scaffold, respectively. Fourteen mammalian 17beta-HSDs have been
      identified so far and nine sequence homologs are found in zebrafish. 17beta-HSDs
      additionally active in fatty acid metabolism display high sequence conservation
      and widespread tissue expression. Homologs of these multifunctional 17beta-HSDs
      have been identified in flies, worms and yeast, and steroid-converting activity
      was demonstrated in some cases. The "classical" 17beta-HSDs, types 1, 2 and 3,
      are steroid-specific enzymes expressed in few tissues. They may have arisen at
      the beginning of vertebrate evolution allowing new, differently controlled modes
      of steroid hormone action. These findings reflect on two aspects: (1) the
      evolutionary origin of steroid-specific enzymes and (2) a possible conservation
      of steroid hormone function in invertebrates through currently unknown
      mechanisms.

PMID- 19111900
TI  - Amyloid beta concentrations in older people with Down syndrome and dementia.
AB  - People with Down syndrome develop Alzheimer's disease with an early age of onset.
      Plasma amyloid beta (Abeta) levels were measured in individuals with Down
      syndrome who were over the age of 40. No associations between age and Abeta1-40
      and Abeta1-42 concentrations were found and nor were Abeta1-40 and Abeta1-42
      levels found to vary between those with Alzheimer's-type dementia and those
      without dementia. The APOE genotype was not found to have an impact upon Abeta1
      40 or Abeta1-42 concentrations. These data suggest that other factors play
      important roles in determining the onset and progression of dementia in the Down
      syndrome population.

PMID- 19111901
TI  - Blockade of NMDA receptor channels by 9-aminoacridine and its derivatives.
AB  - 9-Aminoacridine is known as "foot-in-the-door" NMDA receptor channel blocker
      because its binding prevents channel closure. Structural determinants of this
      mechanism of block were studied using a series of 9-aminoacridine derivatives.
      Experiments were performed on native NMDA receptors of hippocampal pyramidal
      neurons, isolated from rat brain slices. The use-dependence of block and kinetics
      of recovery from block were used to characterize mechanism of block produced by
      the compounds. Modifications, which preserve the flat structure of the tricyclic
      9-aminoacridine moiety, affect blocking activity and kinetics but not the foot-in
      the-door mechanism. On the contrary, disruption of the flat structure changes the
      mechanism of block to trapping. It is concluded that flat aromatic structure is
      one of the critical determinants of the action mechanism of 9-aminoacridine.

PMID- 19111902
TI  - Diffusion tensor tractography can predict hemiparesis in infants with high risk
      factors.
AB  - Diffusion tensor tractography (DTT) is known to be useful in detecting white
      matter lesions. In the current study, we report on two hemiparetic patients with
      risk factors who showed abnormalities of the corticospinal tract (CST) on
      diffusion tensor tractography (DTT) prior to the manifestation of hemiparesis.
      Two hemiparetic patients with risk factors (preterm, low birth weight) and six
      age-matched normal control subjects were enrolled to this study. Diffusion tensor
      imaging (DTI) was performed at the age of 43 weeks (patient 1) and 33 weeks
      (patient 2) using 1.5-T with a Synergy-L Sensitivity Encoding (SENSE) head coil.
      We measured fractional anisotropy (FA), apparent diffusion coefficients (ADCs),
      and fiber counts of the CST. There were no definite asymmetric findings on
      physical examination and conventional brain MRI. By contrast, DTT showed a
      unilateral CST disruption at the periventricular white matter, low FA values, and
      low CST fiber counts compared with those of the unaffected CST and controls.
      These patients were diagnosed with hemiparetic cerebral palsy when we re
      evaluated these patients at the age of 6 years (patient 1) and 3 years of age
      (patient 2), respectively. In these two patients, DTT revealed abnormalities of
      the CST prior to the manifestation of hemiparesis. Therefore, it seems that DTT
      would be a useful modality in detecting CST abnormalities in advance of clinical
      manifestation in infants with high risk factors.

PMID- 19111903
TI  - Endothelin-1 exposure on postnatal day 7 alters expression of the endothelin B
      receptor and behavioral sensitivity to endothelin-1 on postnatal day 11.
AB  - Endothelin (ET)-1 is a chemical mediator released by the body at sites of injury
      and disease and is involved in various painful states. This study examined
      whether ET-1 exposure in the neonatal period alters subsequent ET-1 induced
      nociception and expression of the ET(B) receptor. ET-1 or saline was administered
      to postnatal day 7 rats. On postnatal day 11, ET-1 or saline was administered; a
      first exposure to ET-1 for one group, and a second exposure to ET-1 for another
      group. A statistically significant increase in ET-1 induced paw flinching was
      observed in postnatal day 11 male rats exposed to ET-1 for the second time as
      compared to male rats exposed to ET-1 for the first time. In contrast, a
      statistically significant decrease in ET-1 induced paw flinching was observed in
      postnatal day 11 female rats exposed to ET-1 for the second time as compared to
      female rats exposed to ET-1 for the first time. Furthermore, in males a positive
      correlation was found between ET-1 induced paw flinching on postnatal day 7
      versus 11. In contrast, in females a negative correlation was found between ET-1
      induced paw flinching on postnatal day 7 versus 11. Changes in behavioral
      sensitivity to ET-1 were accompanied by sex-specific ET-1 induced changes in
      expression of the ET(B) receptor on postnatal day 11 in the plantar hind paw with
      a statistically significant decrease and increase in ET(B) receptor expression in
      males and females, respectively. These findings suggest that ET-1 exposure in the
      neonatal period sex-specifically alters expression of the ET(B) receptor and
      behavioral sensitivity to ET-1 whereby males show sensitization and females show
      de-sensitization.

PMID- 19111904
TI  - Activation of muscarinic M-3 receptor may decrease glucose uptake and lipolysis
      in adipose tissue of rats.
AB  - Role of muscarinic receptor in the regulation of glucose uptake or lipolysis in
      adipose tissue remained unclear. In epididymal white adipose tissue (WAT)
      isolated from Wistar rats, we observed that acetylcholine (ACh) attenuated the
      insulin-stimulated glucose uptake and the release of glycerol from WAT in a
      concentration-dependent manner. Using the blockade of specific antagonists, both
      actions of ACh were characterized mainly due to an activation of M3 receptors. In
      the presence of various inhibitors for PLC-PKC pathway, ACh-decreased glucose
      uptake was also reversed. Taken together, these results suggest that muscarinic
      M3 receptor is involved in the regulation of glucose uptake and/or lipolysis in
      adipose tissue.

PMID- 19111905
TI  - Rod-cone dystrophy with maculopathy in genetic glutathione synthetase deficiency:
      a morphologic and electrophysiologic study.
AB  - PURPOSE: To describe the retinal findings in 2 young adults with glutathione
      synthetase (GS) deficiency, an autosomal-recessive inborn error of glutathione
      (GSH) metabolism. DESIGN: Report of 2 cases. PARTICIPANTS: Binocular study in 2
      affected siblings. METHODS: Two sisters with severe GS deficiency underwent a
      first ophthalmologic examination including full-field electroretinogram (ERGs).
      The single flash and flicker ERGs and the oscillatory potentials were measured.
      The clinical examination was repeated after 1 year with the addition of
      fluorescein angiography, optical coherence tomography (OCT), and
      electrooculography (EOG). MAIN OUTCOME MEASURES: Angiograms and the retinal OCTs
      were analyzed, the morphologic findings compared, and the Arden ratio measured.
      RESULTS: Myopia decreased in both sisters, and visual acuity remained unchanged.
      Ophthalmoscopy showed bilateral retinal degenerative changes. Binocular cystic
      macular edema was present in the fovea and perifoveal areas. Cystic changes were
      located in the inner nuclear layer and outer plexiform layer. The ERGs showed low
      or no recordable rod-isolated b-waves, mixed rod-cone a- and b-waves, and cone
      responses. The oscillatory potentials were subnormal or nonrecordable. The EOG
      values were subnormal except in 1 eye of the older sister that had a normal Arden
      ratio. CONCLUSIONS: Severe GS deficiency is associated with progressive retinal
      dystrophy of the rod-cone type, affecting the central retina with advanced
      macular edema in adulthood. The retinal degenerative changes in GS deficiency may
      be the result of the increased oxidative stress accumulated generally in the
      retina and also apparent in the macular area, and an insufficient level of the
      free radical scavenger GSH. The patients with GS deficiency may represent a model
      of the retinal response to oxidative stress in humans. FINANCIAL DISCLOSURE(S):
      The authors have no proprietary or commercial interest in any materials discussed
      in this paper.

PMID- 19111906
TI  - Perception of prosodic hierarchical boundaries in Mandarin Chinese sentences.
AB  - The current study aimed at investigating the processing of prosodic hierarchical
      boundaries in Mandarin Chinese sentences using electroencephalography, mainly
      focused on the following questions: (1) whether prosodic boundaries at different
      levels could evoke the closure positive shift reflecting prosodic boundary
      perception; (2) what were the differences between them at latency, amplitude and
      topography; (3) whether this positive component was modified by the variations of
      acoustic cues (e.g. pause). Main results were: (1) As the previous studies
      indicated, intonational phrases elicited the closure positive shift as a marker
      of online speech structuring; (2) phonological phrases evoked the same positive
      effect with shorter onset latency and somewhat lower amplitude; (3) when the
      pauses in the vicinity of prosodic boundaries were entirely removed, the original
      latency difference between the two conditions disappeared, which clearly
      demonstrated the influence of pause on prosodic boundary processing; (4) prosodic
      word boundaries only induced amplitude variation waving around the baseline,
      which was more positive compared with the one elicited by syllable boundaries.
      The present results indicated that listeners were very sensitive to both
      intonational phrase boundaries and phonological phrase boundaries.

PMID- 19111907
TI  - Elevated 5-HT 2A receptors in postmortem prefrontal cortex in major depression is
      associated with reduced activity of protein kinase A.
AB  - Previous human postmortem brain tissue research has implicated abnormalities of 5
      HT receptor availability in depression and suicide. Although altered abundance of
      5-HT 1A, 5-HT 2A, and 5-HT 2C receptors (5-HT(1A), 5-HT(2A), and 5-HT(2C)) has
      been reported, the causes remain obscure. This study evaluated the availability
      of these three receptor subtypes in postmortem brain tissue specimens from
      persons with a history of major depression (MDD) and normal controls and tested
      the relationships to protein kinases A and C (PKA, PKC). Samples were obtained
      from postmortem brain tissue (Brodmann area 10) from 20 persons with a history of
      MDD and 20 matched controls as determined by a retrospective diagnostic
      evaluation obtained from family members. Levels of 5-HT(1A), 5-HT(2A), and 5
      HT(2C) receptor were quantitated via Western blot analyses. Basal and stimulated
      PKA and PKC activity were also determined. The depressed samples showed
      significantly increased 5-HT(2A) receptor abundance relative to controls, but no
      differences in 5-HT(1A) or 5-HT(2C) receptors. Basal and cyclic AMP-stimulated
      PKA activity was also reduced in the depressed sample; PKC activity was not
      different between groups. 5-HT(2A) receptor availability was significantly
      inversely correlated with PKC activity in controls, but with PKA activity in the
      depressed sample. Increased 5-HT(2A) receptor abundance and decreased PKA
      activity in the depressed sample are consistent with prior reports. The
      correlation of 5-HT(2A) receptor levels with PKA activity in the depressed group
      suggests that abnormalities of 5-HT(2A) receptor abundance may depend on receptor
      uncoupling and heterologous regulation by PKA.

PMID- 19111908
TI  - New experimental model of acute aqueductal blockage in cats: effects on
      cerebrospinal fluid pressure and the size of brain ventricles.
AB  - It is generally assumed that cerebrospinal fluid (CSF) is secreted in the brain
      ventricles, and so after an acute blockage of the aqueduct of Sylvius an increase
      in the ventricular CSF pressure and dilation of isolated ventricles may be
      expected. We have tested this hypothesis in cats. After blocking the aqueduct, we
      measured the CSF pressure in both isolated ventricles and the cisterna magna, and
      performed radiographic monitoring of the cross-sectional area of the lateral
      ventricle. The complete aqueductal blockage was achieved by implanting a plastic
      cannula into the aqueduct of Sylvius through a small tunnel in the vermis of the
      cerebellum in the chloralose-anesthetized cats. After the reconstitution of the
      occipital bone, the CSF pressure was measured in the isolated ventricles via a
      plastic cannula implanted in the aqueduct of Sylvius and in the cisterna magna
      via a stainless steel cannula. During the following 2 h, the CSF pressures in the
      isolated ventricles and cisterna magna were identical to those in control
      conditions. We also monitored the ventricular cross-sectional area by means of
      radiography for 2 h after the aqueductal blockage and failed to observe any
      significant changes. When mock CSF was infused into isolated ventricles to
      imitate the CSF secretion, the gradient of pressure between the ventricle and
      cisterna magna developed, and disappeared as soon as the infusion was terminated.
      However, when mock CSF was infused into the cisterna magna at various rates, the
      resulting increased subarachnoid CSF pressure was accurately transmitted across
      the brain parenchyma into the CSF of isolated ventricles. The lack of the
      increase in the CSF pressure and ventricular dilation during 2 h of aqueductal
      blockage suggests that aqueductal obstruction by itself does not lead to
      development of hypertensive acute hydrocephalus in cats.

PMID- 19111909
TI  - Anticonvulsant properties of saponins from Ficus platyphylla stem bark.
AB  - Preparations of Ficus platyphylla have been used in Nigerian traditional medicine
      for the management of epilepsy for many years and their efficacy is widely
      acclaimed among the Hausa communities of northern Nigeria. The anticonvulsant
      properties of the saponin rich fraction (SFG) obtained from the methanol extract
      of F. platyphylla stem bark were studied on pentylenetetrazole-, strychnine- and
      maximal electroshock seizures in mice. Effects of SFG were also examined in
      murine models for neurological disease and on relevant in vitro targets for
      anticonvulsant drugs. SFG protected mice against pentylenetetrazole- and
      strychnine-induced seizures; and significantly delayed the onset of myoclonic
      jerks and tonic seizures. SFG failed to protect mice against maximal electroshock
      seizures at doses tested. SFG neither abolished the spontaneous discharges
      induced by 4-aminopyridine in a neonatal rat brain slice model of tonic-clonic
      epilepsy nor could it modulate chloride currents through GABA(A) receptor channel
      complex in cultured cortical cells. However, it was able to non-selectively
      suppress excitatory and inhibitory synaptic traffic, blocked sustained repetitive
      firing (SRF) and spontaneous action potential firing in these cultured cells. Our
      results provide scientific evidence that F. platyphylla stem bark may contain
      psychoactive principles with potential anticonvulsant properties. SFG impaired
      membrane excitability; a property shared by most anticonvulsants particularly the
      voltage-gated sodium channel (VGSC) blocking drugs, thus supporting the isolation
      and development of the saponin components of this plant as anticonvulsant agents.

PMID- 19111910
TI  - Brain-derived neurotrophic factor, stress and depression: a minireview.
AB  - Brain-derived neurotrophic factor (BDNF) is a member of the nerve growth factor
      family, and is widely expressed in the adult mammalian brain. Besides its well
      known neuroprotective activity after traumatic brain injury the evidences
      regarding its activity dependent release by the pathophysiology of major
      depression are rapidly replicating. Considering the data that stress plays an
      important role by the development of depression which is characterized with
      prominent hippocampal cell death, as well as the well known neuroprotective
      effects of BDNF, we aimed to investigate the link between the BDNF, stress and
      depression. Thus we prepared a minireview in order to evaluate the
      neuroprotective role of BDNF by psychiatric disorders which are characterized
      with prominent neuronal cell death.

PMID- 19111911
TI  - The distribution of kisspeptin and its receptor GPR54 in rat dorsal root ganglion
      and up-regulation of its expression after CFA injection.
AB  - Kisspeptin/GPR54 system plays a crucial role in the control of puberty onset and
      reproductive function. In the present study, we gave the first report that
      kisspeptin and GPR54 were expressed in the small- to large-sized neurons, and co
      localized with Bandeiraea simplicifolia isolectin B4 (IB4), calcitonin-gene
      related peptide (CGRP) and neurofilament 200 (NF200) in the L4/5 dorsal root
      ganglion (DRG) of naive rats, detected by the double immunofluorescent staining.
      Interestingly, a marked elevation in the levels of KiSS-1 and GPR54 mRNA as well
      as protein was observed in the spinal dorsal horn and DRG 4 and 14 days following
      intra-articular injection of complete Freund's adjuvant (CFA), indicating a
      possible involvement of the kisspeptin/GPR54 system in chronic inflammatory pain.

PMID- 19111912
TI  - Expression of the LIM-homeodomain gene Lmx1a in the postnatal mouse central
      nervous system.
AB  - The LIM-homeodomain transcription factor Lmx1a plays critical roles in roof plate
      formation as well as in the cell fate determination of midbrain dopaminergic
      neurons during embryonic development, but its function in the adult brain remains
      unknown. In the present study, as the first step in exploring its function in
      adult brain, we examined the expression of Lmx1a in the mouse central nervous
      system (CNS) from birth to adulthood by in situ hybridization. Lmx1a was
      expressed at high levels in the posterior hypothalamic area, supremammillary
      nucleus, ventral premammillary nucleus, subthalamic nucleus, ventral tegmental
      area, compact part of the substantia nigra and parabrachial nucleus from birth to
      adulthood, and co-localized with its paralogue Lmx1b in these regions. On the
      other hand, Lmx1a expression in the cochlear nuclei, medial cerebellar nucleus
      and superior vestibular nucleus was only observed until postnatal day (P) 30 and
      showed no colocalization with Lmx1b. Lmx1a-expressing neurons in the ventral
      midbrain were dopaminergic as evidenced by co-expression with tyrosine
      hydroxylase in these regions. Furthermore, Lmx1a expression was also found in the
      choroid plexuses and ependymal cells, although its expression was only detected
      during the first two postnatal weeks. These results suggest that Lmx1a may be
      involved in postnatal development as well as in maintenance of some aspects of
      normal brain function.

PMID- 19111913
TI  - Maternal and contextual influences and the effect of temperament development
      during infancy on parenting in toddlerhood.
AB  - In the current study, latent growth modeling (LGM) was used to: (1) identify the
      developmental trajectories of infant negative emotions (NE) and regulatory
      capacity (RC) from 4 to 12 months of age, (2) examine maternal and family factors
      that may affect NE and RC trajectories, (3) examine transactional associations
      between developing NE and RC, and (4) examine the effect of infant temperament
      trajectories on negative parenting when toddlers reached 18 months of age.
      Mothers from 156 families completed a measure of infant temperament when infants
      were 4, 6, 8, 10, and 12 months of age and completed maternal relationship
      stress, depression, and family demographics measures when infants were 4 months
      of age. Information regarding negative parenting was collected when toddlers
      reached 18 months of age. LGM results suggest that maternal relationship stress
      and depression influence infant NE development, that high NE early in infancy may
      compromise the development of infant regulation, and that steeper decreases of
      infant RC contribute the greatest amount of variance to negative parenting in
      toddlerhood. The implications for models of early emotion regulation and
      incorporating changes in temperament over time into developmentally sensitive
      models (e.g., emerging parenting practices and developmental psychopathology) are
      discussed.

PMID- 19111914
TI  - Reinforcer satiation and resistance to change of responding maintained by
      qualitatively different reinforcers.
AB  - In previous research on resistance to change, differential disruption of operant
      behavior by satiation has been used to assess the relative strength of responding
      maintained by different rates or magnitudes of the same reinforcer in different
      stimulus contexts. The present experiment examined resistance to disruption by
      satiation of one reinforcer type when qualitatively different reinforcers were
      arranged in different contexts. Rats earned either food pellets or a 15% sucrose
      solution on variable-interval 60-s schedules of reinforcement in the two
      components of a multiple schedule. Resistance to satiation was assessed by
      providing free access either to food pellets or the sucrose solution prior to or
      during sessions. Responding systematically decreased more relative to baseline in
      the component associated with the satiated reinforcer. These findings suggest
      that when qualitatively different reinforcers maintain responding, relative
      resistance to change depends upon the relations between reinforcers and disrupter
      types.

PMID- 19111915
TI  - Effects of the brominated flame retardant hexabromocyclododecane (HBCD) on
      dopamine-dependent behavior and brainstem auditory evoked potentials in a one
      generation reproduction study in Wistar rats.
AB  - Hexabromocyclododecane (HBCD) is a widely used brominated flame retardant which
      has been recently detected in many environmental matrices. Data from a subacute
      toxicity study indicated dose-related effects particularly on the pituitary
      thyroid-axis and retinoids in female rats. Brominated and chlorinated aromatic
      hydrocarbons are also reported to exert effects on the nervous system. Several
      investigations revealed a pronounced sensitivity of the dopaminergic system and
      auditory functions to polychlorinated biphenyls. Therefore, the present
      experiment should examine, whether or not HBCD affects these targets. Rats were
      exposed to 0, 0.1, 0.3, 1, 3, 10, 30 or 100 mg HBCD/kg body weight via the diet.
      Exposure started before mating and was continued during mating, gestation,
      lactation, and after weaning in offspring. Haloperidol-induced catalepsy and
      brainstem auditory evoked potentials (BAEPs) were used to assess dopamine
      dependent behavior and hearing function in adult male and female offspring. On
      the catalepsy test, reduced latencies to movement onset were observed mainly in
      female offspring, indicating influences on dopamine-dependent behavior. The
      overall pattern of BAEP alterations, with increased thresholds and prolonged
      latencies of early waves, suggested a predominant cochlear effect. Effects were
      dose-dependent with lower bounds of benchmark doses (BMDL) between < or =1 and 10
      mg/kg body weight for both catalepsy and BAEP thresholds. Tissue concentrations
      at the BMDL values obtained in this study were 3-4 orders of magnitude higher
      than current exposure levels in humans.

PMID- 19111916
TI  - Oculoauriculovertebral complex with an atypical cause of obstructive sleep apnea.
AB  - Oculoauriculovertebral spectrum (OAVS) is a birth defect of unknown etiology,
      often causing obstructive sleep apnea, due to unilateral retrognathia. We
      describe an adolescent sleep apnea patient, with usual and unusual signs of OAVS.
      Apart from mandibular hypoplasia, microtia, external auditory canal atresia and
      cervical vertebrae anomalies, skull base asymmetry was also noted, resulting in
      aberrant anatomy of the tympanic cavity, and nasopharyngeal obstruction, which
      was the main source of the patient's apneas. The extended craniofacial
      abnormalities manifested here, suggest a broader developmental impairment,
      exceeding the 1st and 2nd branchial arch malformation theory, which is the
      principal hypothesis for OAVS etiology.

PMID- 19111917
TI  - Effect of aqueous suspension of dried latex of Calotropis procera on hepatorenal
      functions in rat.
AB  - AIM OF THE STUDY: The present study was carried out to evaluate the effect of dry
      latex (DL) of Calotropis procera, a plant of the family Asclepiadaceae, on the
      functions of liver and kidney in normal rats. MATERIALS AND METHODS: Aqueous
      suspension of DL was orally administered to rats at doses of 10, 100 and 400
      mg/kg for a period of 45 days and the effect on various parameters reflecting
      liver and kidney functions was compared with that of normal controls. RESULTS:
      Treatment with DL did not alter the serum levels of aspartate transaminase (AST),
      alanine transaminase (ALT), alkaline phosphatase (ALP), creatinine, urea and
      urinary levels of glucose and protein as compared to the normal rats. It
      exhibited a modulatory role in maintaining the levels of blood glucose and serum
      insulin. The liver and kidney of DL treated and normal rats were also comparable
      with regard to the tissue levels of oxidative stress markers and histology.
      Further, no signs of toxicity were observed in the DL treated rats over the study
      period. CONCLUSION: Our study reveals that aqueous suspension of Calotropis
      procera latex does not produce any toxicity and could be safely used for
      therapeutic purpose at the doses studied.

PMID- 19111918
TI  - Studies on the analgesic, anti-inflammatory and antipyretic effects of Parquetina
      nigrescens leaf extract.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: Parquetina nigrescens is a shrub that is commonly
      used in different parts of West Africa for the treatment of several ailments
      which includes pain, fever and inflammatory conditions. AIM OF THE STUDY: The
      present study was designed to investigate the analgesic, anti-inflammatory and
      antipyretic effects of the aqueous extract of Parquetina nigrescens leaves in
      rats. MATERIALS AND METHODS: Five groups were used for each study, groups 1 and 5
      served as control (saline) and reference (indomethacine) respectively, while
      groups 2-4 received the extract (50-200 mg/kg) orally. Formalin paw licking and
      hot plate latency tests were used for analgesic studies. Carrageenan oedema,
      cotton pellet granuloma and formaldehyde arthritis models were used to quantify
      the anti-inflammatory activities while the brewer's yeast was used for inducing
      pyrexia. RESULTS: The results of the analgesic study show that the extract
      produced significant (p<0.05) analgesia in the hot plate and in the formalin
      tests. In the anti-inflammatory study, Parquetina nigrescens produced significant
      (p<0.05) inhibition of the various types of inflammation. The extract also
      inhibited the pyrexia induced by brewer's yeast. CONCLUSION: The result justifies
      the traditional uses of Parquetina nigrescens for the treatment of fever,
      inflammatory and painful conditions.

PMID- 19111920
TI  - The free-living flatworm Macrostomum lignano: a new model organism for ageing
      research.
AB  - To study the several elements and causes of ageing, diverse model organisms and
      methodologies are required. The most frequently used models are Saccharomyces
      cerevisiae, Caenorhabditis elegans, Drosophila melanogaster and rodents. All have
      their advantages and disadvantages and allow studying particular aspects of the
      ageing process. During the last few years, several ageing studies focussed on
      stem cells and their role in tissue homeostasis. Here we present a new model
      organism which can study this relation where other model systems fail. The
      flatworm Macrostomum lignano possesses a dynamic population of likely totipotent
      somatic stem cells known as neoblasts. Several characteristics qualify M. lignano
      as a suitable model system for ageing studies in general and more specifically
      for gaining more insight in the causal relation between stem cells, ageing and
      rejuvenation. In this review, we will briefly describe the species and its life
      history, and discuss the role of its stem cells in ageing and rejuvenation. We
      also give an overview of the available experimental tools that allow a
      multidisciplinary approach for studying ageing in M. lignano.

PMID- 19111919
TI  - The production of nitric oxide and prostaglandin E2 in peritoneal macrophages is
      inhibited by Andrographis paniculata, Angelica sinensis and Morus alba ethyl
      acetate fractions.
AB  - AIM OF THE STUDY: Traditional Chinese medicine herbs (TCMHs) are used in
      medicines as well as in daily dietary supplements in Asia. In this study, we
      employed pNF-kappaB-Luc or pIFN-gamma-Luc and BALB/c mice peritoneal macrophages
      or splenocytes to investigate both the immune and inflammatory effects of six
      selected plant species. MATERIALS AND METHODS: Specifically, we used ethyl
      acetate fractions of Astragalus membranaceus (Fisch.) Bunge var. mongholicus
      (Bunge) Hsiao (Fabaceae) (AM), Andrographis paniculata (Burm. f.) Nees
      (Acanthaceae) (AP), Angelica sinensis (Oliv.) Diels (Apiaceae) (AS), Eucommia
      ulmodes Oliv. (Eucommiaceae) leaves (EU leaves), Isatis indigotica Fort.
      (Brassicaceae) (II) and Morus alba L. (Moraceae) (MA). RESULTS: We found that
      ethyl acetate fractions of AP, AS and MA significantly decreased NF-kappaB
      luciferase activity and also the secretion of NO and PGE(2) in LPS/IFN-gamma
      stimulated mouse peritoneal macrophages (p<0.05). In contrast, they did not
      affect IFN-gamma luciferase activity or IFN-gamma production in concanavalin A
      (Con A)-activated mouse splenocytes. Our results indicated that the anti
      inflammatory properties of these plant extracts might be resulted from the
      inhibition of pro-inflammatory mediators (e.g., NO and PGE(2)), at least in part
      via suppression of a signaling pathway such as NF-kappaB. CONCLUSIONS:
      Collectively, we have found that three potent bioactive TCMH species exerted
      significant NF-kappaB inhibitory activity and acted in a cell type dependent
      fashion.

PMID- 19111921
TI  - Effects of two oils and 16 pure polycyclic aromatic hydrocarbons on plasmatic
      immune parameters in the European sea bass, Dicentrarchus labrax (Linne).
AB  - The in vitro effects of polycyclic aromatic hydrocarbons (PAHs) on two plasmatic
      immune parameters, lysozyme concentration and haemolytic alternative complement
      activity, of the European sea bass, Dicentrarchus labrax, were tested using field
      (10(-7) and 10(-9) mg mL(-1)) and high concentrations (10(-3) and 10(-5) mg mL(
      1)) observed during oil spills. Peripheral blood from 105 fish was collected,
      centrifuged at 1200 g, for 10 min, at 4 degrees C and three plasma pools, each of
      35 fish, were constituted. Two oils (heavy fuel oil and light cycle oil) and 16
      pure PAHs, selected on the basis of the American Environmental Protection Agency
      list (US EPA), were tested in vitro on the two humoral immune parameters. Only
      three pure PAHs (anthracene, chrysene and dibenz[a,h]anthracene) modulated
      lysozyme concentration. Acenaphthene, acenaphthylene, anthracene,
      benzo[a]anthracene, benzo[a]pyrene, benzo[b]fluoranthene, benzo[k]fluoranthene,
      pyrene and light cycle oil modified the haemolytic alternative complement
      activity after 4h of incubation. This study investigates the direct effects of
      several PAHs on fish humoral immune functions and describes the haemolytic
      complement activity of fish as suitable biomarkers of oil pollution.

PMID- 19111923
TI  - Association of peripheral inflammatory markers with chronic fatigue in a
      population-based sample.
AB  - Alterations in the innate immune response may contribute to the pathogenesis of
      chronic fatigue syndrome (CFS). However, studies have been limited by small
      sample sizes, use of patients from tertiary care settings, inappropriate
      selection of controls, and failure to control for confounding demographic,
      medical and behavioral factors independently associated with immune activity. It
      is also not known whether specific symptoms account for observed associations
      between CFS and the innate immune response. To address these limitations, the
      current study examined plasma concentrations of high-sensitivity c-reactive
      protein (hs-CRP), white blood cell count (WBC) and a combined inflammation factor
      in a large population-based sample. Log-transformed mean plasma concentrations of
      hs-CRP were increased in subjects with CFS (n=102) and in subjects with
      unwellness symptoms that did not meet diagnostic criteria for CFS (defined as
      "insufficient fatigue" [ISF]) (n=240) when compared to subjects who were well
      (n=115). Log transformed WBC was increased in ISF and was increased at a trend
      level in CFS. The combined inflammation factor was increased in both CFS and ISF.
      Subjects with CFS and ISF did not differ on any of the inflammation measures. In
      the entire subject population, the physical component summary score (PCS), but
      not the mental component summary score (MCS), from the Medical Outcomes Study
      Short Form-36 (SF-36) was negatively associated with each of the inflammation
      measures. Depressive symptoms were also associated with increased log hs-CRP.
      After adjustment for age, sex, race, location of residence, BMI, depressive
      status and immune-modulating medications, subjects classified as ISF continued to
      demonstrate increased log hs-CRP, WBC and elevations on the inflammation factor
      when compared to well controls; however, associations between CFS and log hs-CRP
      and the inflammation factor were no longer statistically significant. After
      adjustment, PCS score also remained independently associated with each of the
      inflammation measures. These findings support a role for innate immune activation
      in unexplained fatigue and unwellness, but do not suggest that immune activation
      is specific to CFS.

PMID- 19111922
TI  - Pessimism correlates with leukocyte telomere shortness and elevated interleukin-6
      in post-menopausal women.
AB  - The combination of less positive and more negative expectations for the future
      (i.e., lower optimism and higher pessimism) increases risk for disease and early
      mortality. We tested the possibility that expectancies might influence health
      outcomes by altering the rate of biological aging, specifically of the immune
      system (immunosenescence). However, no studies to date have examined associations
      between optimism or pessimism and indicators of immunosenescence such as
      leukocyte telomere length (TL) and interleukin-6 (IL-6) levels. We investigated
      whether dispositional tendencies towards optimism and pessimism were associated
      with TL and IL-6 in a sample of 36 healthy post-menopausal women. Multiple
      regression analyses where optimism and pessimism were entered simultaneously, and
      chronological age and caregiver status were controlled, indicated that pessimism
      was independently associated with shorter TL (beta=-.68, p=.001) and higher IL-6
      concentrations (beta=.50, p=.02). In contrast, optimism was not independently
      associated with either measure of immunosenescence. These findings suggest that
      dispositional pessimism may increase IL-6 and accelerate rate of telomere
      shortening. Mechanistic causal relationships between these parameters need to be
      investigated.

PMID- 19111924
TI  - Retrograde and anterograde transport of HIV protein gp120 in the nervous system.
AB  - Neurodegeneration and gliosis are prominent pathological features of subjects
      with human immunodeficiency virus (HIV) dementia complex (HAD). In these
      patients, neurodegeneration occurs in uninfected neurons. In addition, these
      patients develop sensory neuropathy despite the antiretroviral therapy. The HIV
      protein gp120, which mimics some of the pathological alterations seen in HAD, is
      retrogradely transported in rodent neurons. However, it is still unclear whether
      gp120 can also be transported anterogradely and whether axonal transport can
      occur in the peripheral nervous system (PNS). To determine whether gp120 is
      transported retrogradely and/or anterogradely, we injected gp120IIIB together
      with the retrograde tracer fluoro-ruby (FR) or the anterograde tracer 1,1'
      dioctadecyl-3,3,3',3'-tetramethylindocarbocyamine perchlorate (DiI) into the rat
      superior colliculi. We discovered that gp120 is retrogradely transported with FR
      along a direct pathway from the superior colliculus to the retina and
      anterogradely transported with DiI to several areas of the occipital cortex. To
      determine whether gp120 is also axonally transported in the peripheral nerves,
      gp120 and FR were injected into the sciatic nerve. No gp120 immunoreactivity was
      found in the sciatic nerve or dorsal root ganglia, suggesting that gp120 axonal
      transport does not occur in the PNS. Gp120 axonal transport may play a role in
      neuronal injury. Therefore, we examined apoptosis at various time points after
      gp120 injection. Activated caspase-3 was evident within neurons transporting
      gp120. These results indicate that axonal transport of gp120 might exacerbate the
      pathogenesis of HIV-1.

PMID- 19111926
TI  - Gene synthesis demystified.
AB  - DNA fabrication of genetic cassettes at base-level precision is transforming
      genetic engineering from a laborious art to an information-driven discipline.
      Although substantial advances have been made in the development of DNA
      fabrication, the methods employed vary widely based on the length of the DNA. All
      of these methods are available commercially, but can also be performed at the
      molecular biology bench using typical reagents and procedures. Because the
      technology is not mature and is still evolving rapidly, it is helpful to gain
      some understanding of the different steps in this process and the associated
      technical challenges to successfully take advantage of DNA fabrication in a
      research project.

PMID- 19111925
TI  - Sex hormones and mucosal wound healing.
AB  - Wound healing studies, which have chiefly examined dermal tissues, have reported
      a female advantage in healing rates. In contrast, our laboratory recently
      demonstrated women heal mucosal wounds more slowly than men. We hypothesized sex
      hormones influence wound healing rates, possibly through their modulating effects
      on inflammation. This study involved 329 younger subjects aged 18-43 (165 women,
      164 men) and 93 older subjects aged 50-88 (60 women, 33 men). A 3.5mm diameter
      wound was created on the hard oral palate and videographed daily to assess wound
      closure. Blood collected at the time of wounding was used to assess circulating
      testosterone, progesterone and estradiol levels, and in vitro cytokine production
      in response to LPS. No strong associations were observed between healing times
      and estradiol or progesterone levels. However, in younger subjects, lower
      testosterone levels related to faster wound closure. Conversely, in older women
      higher testosterone levels related to (1) lower inflammatory responses; and (2)
      faster healing times. No such relationships were seen in older men, or in women
      taking oral contraceptives or hormone replacement therapy [HRT]. Older women (50
      54 years) not yet experiencing menopause healed similarly to younger women and
      dissimilarly from age-matched post-menopausal women. This suggests that the
      deleterious effects of aging on wound healing occur secondary to the effects of
      menopause. Supporting this, there was evidence in post-menopausal women that HRT
      augmented wound closure. Overall, this study suggests that human mucosal healing
      rates are modulated by testosterone levels. Based upon when between-group
      differences were observed, testosterone may impact upon the proliferative phase
      of healing which involves immune processes such as re-epithelialization and
      angiogenesis.

PMID- 19111927
TI  - Methanol-based industrial biotechnology: current status and future perspectives
      of methylotrophic bacteria.
AB  - Methanol is one of the building blocks in the chemical industry and can be
      synthesized either from petrochemical or renewable resources, such as biogas.
      Bioprocess technology with methylotrophic bacteria is well established, as
      illustrated by large-scale single-cell protein production in the past. During
      recent years, the first genomes of methylotrophs have been sequenced and
      significant progress in elucidating their metabolism has been made. In addition,
      the tool set for genetic engineering of methylotrophic bacteria has expanded
      greatly and strategies to produce fine and bulk chemicals with methylotrophs have
      been described. This review highlights the potential of these bacteria for the
      development of economically competitive bioprocesses based on methanol as an
      alternative carbon source, bringing together biological, technical and economic
      considerations.

PMID- 19111928
TI  - Lipid induced overexpression of NF-kappaB in skeletal muscle cells is linked to
      insulin resistance.
AB  - Lipid induced NF-kappaB activation is known to be associated with insulin
      resistance and type2 diabetes. Here we show that incubation of L6 skeletal muscle
      cells with palmitate significantly increased NF-kappaB p65 and NF-kappaB p50
      expression along with their phosphorylation. NF-kappaB p65 siRNA inhibited
      palmitate induced overexpression of NF-kappaB p65 indicating palmitate effect on
      transcriptional activation. RT-PCR and real time PCR experiments also showed a
      significant increase in NF-kappaB p65 gene expression due to palmitate.
      Overexpression of NF-kappaB p65 by palmitate was linked to impairment of insulin
      activity. Palmitate effect on NF-kappaB gene and protein expression was found to
      be mediated by phospho-PKCepsilon as calphostin C (an inhibitor of PKC) and
      epsilonV1 (PKCepsilon translocation inhibitor) significantly reduced NF-kappaB
      expression. To understand the underlying mechanism, we purified NF-kappaB and
      pPKCepsilon from palmitate incubated skeletal muscle cells and their interaction
      in cell free system demonstrated the transfer of phosphate from PKCepsilon to NF
      kappaB. This prompted us to transduct pPKCepsilon to the skeletal muscle cells.
      These cells showed increased amount of pNF-kappaB and NF-kappaB. Excess of NF
      kappaB p65 pool thus created in the cells made them insulin resistant. Addition
      of NF-kappaB p65 siRNA and SN50 inhibited palmitate induced NF-kappaB p65
      expression indicating NF-kappaB regulation of its gene expression. Increase of NF
      kappaB did not affect the activation of IKK/IkappaB indicating NF-kappaB p65
      expression to be a distinct effect of palmitate. Since NF-kappaB p65 is linked to
      several diseases, including type2 diabetes, this report may be important in
      understanding the pathogenicity of these diseases.

PMID- 19111929
TI  - Development of new lipid-based paclitaxel nanoparticles using sequential simplex
      optimization.
AB  - The objective of these studies was to develop Cremophor-free lipid-based
      paclitaxel (PX) nanoparticle formulations prepared from warm microemulsion
      precursors. To identify and optimize new nanoparticles, experimental design was
      performed combining Taguchi array and sequential simplex optimization. The
      combination of Taguchi array and sequential simplex optimization efficiently
      directed the design of paclitaxel nanoparticles. Two optimized paclitaxel
      nanoparticles (NPs) were obtained: G78 NPs composed of glyceryl tridodecanoate
      (GT) and polyoxyethylene 20-stearyl ether (Brij 78), and BTM NPs composed of
      Miglyol 812, Brij 78, and d-alpha-tocopheryl polyethylene glycol 1000 succinate
      (TPGS). Both nanoparticles successfully entrapped paclitaxel at a final
      concentration of 150 microg/ml (over 6% drug loading) with particle sizes less
      than 200 nm and over 85% of entrapment efficiency. These novel paclitaxel
      nanoparticles were stable at 4 degrees C over five months and in PBS at 37
      degrees C over 102 h as measured by physical stability. Release of paclitaxel was
      slow and sustained without initial burst release. Cytotoxicity studies in MDA-MB
      231 cancer cells showed that both nanoparticles have similar anticancer
      activities compared to Taxol. Interestingly, PX BTM nanocapsules could be
      lyophilized without cryoprotectants. The lyophilized powder comprised only of PX
      BTM NPs in water could be rapidly rehydrated with a complete retention of
      original physicochemical properties, in vitro release properties, and
      cytotoxicity profile. Sequential Simplex Optimization has been utilized to
      identify promising new lipid-based paclitaxel nanoparticles having useful
      attributes.

PMID- 19111930
TI  - Altered levels of adipocytokines in type 2 diabetic cigarette smokers.
AB  - Hyperleptinemia, hypoadiponectinemia, and hyperresistinemia were found to be
      significantly higher with odds ratios (CI 95%) of 2.15, 2.05 and 3.05,
      respectively, among cigarette smokers with type 2 diabetes in Saudi Arabian
      population. Smoking cessation restored the adiponectin and leptin levels while
      having a modest effect on resistin levels.

PMID- 19111931
TI  - Non-lethal Candida albicans cph1/cph1 efg1/efg1 mutant partially protects mice
      from systemic infections by lethal wild-type cells.
AB  - Although Candida albicans cph1/cph1 efg1/efg1 mutant cells are not lethal to
      mice, they proliferated in infected mice instead of simply being cleared by the
      host immune system. Here, we have shown that the cph1/cph1 efg1/efg1 mutant
      partially protects mice from systemic infections by the lethal wild-type Candida
      albicans cells. Our results further indicate that a second dose of the cph1/cph1
      efg1/efg1 mutant did not boost the degree of protection.

PMID- 19111932
TI  - Mucinous versus nonmucinous solitary pulmonary nodular bronchioloalveolar
      carcinoma: CT and FDG PET findings and pathologic comparisons.
AB  - We aimed to evaluate the CT, PET, and pathologic findings of solitary pulmonary
      nodular mucinous and nonmucinous bronchioloalveolar carcinomas (BACs). From
      August 2003 to March 2008, we saw 24 patients with solitary pulmonary nodular
      mucinous (n=6) or nonmucinous (n=18) BACs that were resected. CT and PET findings
      of the lesions were assessed in terms of size, solidity, morphologic
      characteristics, attenuation and maximum standardized uptake value (mSUV). All
      nonmucinous BACs appeared as a pure ground-glass opacity (GGO) nodule, whereas
      mucinous BACs appeared as solid (n=4) or part-solid (n=2) nodules. CT attenuation
      values were significantly higher for mucinous BACs (-21.0 HU+/-4.9) than for
      nonmucinous BACs (-491.8 HU+/-172.5) (P<.001). Mean mSUVs were 2.3+/-1.9 for
      mucinous BACs and 0.5+/-0.8 for nonmucinous BACs (P=.007), but mSUVs were not
      statistically different after size adjustment (r=0.371, P=.081). Mucinous BACs
      appear as solid or part-solid nodules at CT, whereas nonmucinous BACs present as
      pure GGO nodules. Both subtypes of tumors show scant FDG uptake at PET.

PMID- 19111933
TI  - Uterine carcinosarcoma metastatic to the lung as large-cell neuroendocrine
      carcinoma with synchronous sarcoid granulomatosis.
AB  - A 58-year-old woman underwent a curative total abdominal hysterectomy with
      bilateral salpingo-oophorectomy for a uterine carcinosarcoma. Fifteen months
      later, PET and CT scan revealed three pulmonary nodules and multiple
      lymphadenopathy. An atypical lung segmentectomy with dissection of the regional
      lymph nodes was performed. Two of the three nodules showed morphological and
      immunohistochemical profiles consistent with the diagnosis of large-cell
      neuroendocrine carcinoma (LCNEC). The third nodule, the surrounding pulmonary
      parenchyma and lymph nodes showed diffuse sarcoid granulomatosis. Re-review of
      the histology of the uterine carcinosarcoma revealed LCNEC morphology with
      immunohistochemical and genetic profiles identical to the lung cancers, finally
      deemed as metastatic deposits. Systemic sarcoidosis was ruled out. To our
      knowledge this is the first case of uterine carcinosarcoma with LCNEC features
      metastatic to the lung and occurring in association with sarcoid reaction.

PMID- 19111934
TI  - Crystal structures of the apo and holo form of rat catechol-O-methyltransferase.
AB  - Catechol-O-methyltransferase (COMT, EC 2.1.1.6) is a monomeric enzyme that
      catalyzes the transfer of a methyl group from S-adenosyl-l-methionine (AdoMet) to
      the phenolic oxygen of substituted catechols. Although the inhibitor recognition
      pattern and AdoMet site have already been studied crystallographically,
      structural information on the catalytic cycle of COMT has not yet been obtained.
      In this study, comparison of the co-factor and inhibitor-bound structures
      revealed that the Apo form of COMT shows a conformational change and there was no
      cleft corresponding to the AdoMet-binding site; the overall structure was
      partially open form and the substrate recognition site was not clearly defined.
      The Holo form of COMT was similar to the quaternary structure except for the
      beta6-beta7 and alpha2-alpha3 ligand recognition loops. These conformational
      changes provide a deeper insight into the structural events occurring in
      reactions catalyzed by AdoMet.

PMID- 19111935
TI  - Phylogenetic uncertainty and molecular clock calibrations: a case study of
      legless lizards (Pygopodidae, Gekkota).

PMID- 19111936
TI  - Phylogeography of Tibetan snowcock (Tetraogallus tibetanus) in Qinghai-Tibetan
      Plateau.
AB  - Data from eight microsatellite loci were used to infer the evolutionary and past
      demographic processes in 97 Tibetan snowcocks sampled from eight different
      geographical locations on the Qinghai-Tibetan Plateau. Analysis of the
      microsatellite DNA markers indicated that Tibetan snowcock on the plateau were
      geographically structured, and that phylogenetic analyses identified three
      phylogroups, namely those from Xunhua, the Qilian Mountains and all others. The
      use of Bayesian Clustering and Population Assignment analyses of the
      microsatellite genotypes revealed clear differentiation among the eight sampled
      groups of Tibetan snowcock, indicating strong isolation of these sub-populations.
      Therefore, we suggested that the distribution pattern of Tibetan snowcock
      observed today resulted from adaptation to the climatic conditions and glacial
      cycles on the Qinghai-Tibetan Plateau. In addition, BOTTLENECK analysis indicated
      that Tibetan snowcock had recently passed through evolutionary bottlenecks. These
      results suggested that effective conservation measures should be undertaken to
      protect Tibetan snowcock from an increased probability of extinction.

PMID- 19111937
TI  - Effects of cardiorespiratory fitness and cerebral blood flow on cognitive
      outcomes in older women.
AB  - The mechanisms by which aerobic fitness confers beneficial effects on cognition
      with aging are unclear but may involve cerebrovascular adaptations. In a cross
      sectional study of women from the community (n=42; age range=50-90 years), we
      sought to determine whether physical fitness is associated with higher
      cerebrovascular function, and its relationship to cognition. Main outcome
      measures included resting cerebral blood flow, cerebrovascular reserve, physical
      fitness (i.e., VO2max) and cognition. Physically fit women had lower resting mean
      arterial pressure (MAP) and higher cerebrovascular conductance (CVC) than
      sedentary women. Overall cognition was negatively correlated with age and
      positively correlated with VO2max. VO2max was a predictor of resting CVC and MAP,
      and CVC and MAP when end-tidal gases were held constant at near-resting values.
      MAP and CVC were predictors of cognition. This study identified strong
      associations between physical fitness, vascular function and cognition, and
      provides new understanding regarding the mechanisms by which fitness positively
      impacts cognition with aging. The implications of this research are considerable
      and warrant future investigation.

PMID- 19111938
TI  - Spontaneous cardiac arrhythmias recorded in three experimentally- and drug-naive
      laboratory species (canine, primate, swine) during standard pre-study screening.
AB  - INTRODUCTION: The purpose of this study was to collect and estimate the general
      prevalence of spontaneous irregularities in cardiac rhythms in three standard
      laboratory animal species: Beagle dog (N=2450), cynomolgus monkey (N=1563), and
      domestic swine (N=704) during standard preclinical screening. METHODS: Standard
      prestudy Lead II hardwire ECG tracings were collected in purpose-bred, drug-, and
      experimentally-naive animals following receipt from an institutionally-approved
      vendor and prior to placement onto general toxicology or safety pharmacology
      studies over the course of 18 months. The ECGs were independently reviewed by two
      veterinary cardiologists/internists for the presence or absence of arrhythmias
      (dysrhythmia), conduction disturbances, or other normal variants or clinically
      significant waveform changes. RESULTS: Greater than 98% of all ECGs recorded in
      animals bred for laboratory use demonstrated sinus rhythms without morphologic
      abnormalities or arrhythmias.

PMID- 19111939
TI  - A professional practice-based doctorate: Developing advanced nursing practice.

PMID- 19111940
TI  - An evaluation of a collaborative approach to the assessment of competence among
      nursing students of three universities in Ireland.
AB  - This paper describes a collaborative project conducted by the three principal
      universities in Dublin to implement and evaluate a competence assessment tool for
      use by nursing students and their assessors while on clinical placements. In the
      greater Dublin area, students from three universities are required to share
      clinical placement sites in specialist practice areas. Accordingly, a liaison
      group was established among the three universities, in order to develop a common
      competence-based assessment tool and related protocols for its use. The newly
      developed competence assessment tool was implemented in 2004, and in 2006, an
      evaluation of its use was conducted by means of a survey among a non-probability
      sample of students and their preceptors. Results from the survey data indicate
      generally positive attitudes to the structure of the tool and positive
      experiences of its operation in practice. However, respondents indicated
      dissatisfaction with the amount of time spent completing the assessment tool and
      the amount of preparation needed to carry out the assessment process.
      Recommendations for practice include the need to consider placement length in the
      design process and the need to focus on user preparation. This study also points
      to the benefits of inter-institutional collaboration in competence assessment and
      the possible implications for future work in this area.

PMID- 19111941
TI  - Review of continuing professional education in case management for nurses.
AB  - Nineteen studies evaluating the effectiveness of continuing professional
      education programs in case management for nurses were reviewed. The studies were
      examined in terms of their educational focus and strategies, evaluative methods,
      and effectiveness. The programs assessed either focused on the provision of new
      knowledge or skills, or aimed to teach specific case management delivery models.
      The most appropriate program length appears to be at least 16 h. A combination of
      learning strategies, incorporating interactive lectures and small group
      discussions, are often used in case management educational programs and are
      associated with positive learning outcomes. The majority of these studies did not
      have a control group. Future evaluative studies need to incorporate larger sample
      sizes, a variety of evaluation methods and a control group in order to provide a
      valid measure of the effectiveness of continuing professional education in case
      management for nurses.

PMID- 19111942
TI  - New nursing education structure in Spain.
AB  - Nursing education in Spain is developing rapidly in accordance with the European
      Union growth and within an international globalization movement. The purpose of
      this article is to present the new nursing education framework in Spain: A brief
      history together with its recent reform and developments. Since nursing education
      was integrated into the university level in 1977, the only academic recognition
      for such an education in Spain was the three year diploma degree. Nurses had to
      move into other disciplines in order to achieve academic growth or advance their
      nursing studies abroad. Currently and in compliance with the Bologna declaration
      for the Higher European Education Area, nursing education in Spain is being
      transformed into a program which recognizes bachelor, master and doctoral degrees
      in this field. In January 2005, the Spanish Government published the guidelines
      for the undergraduate, master's and doctoral levels, and finally, last October
      2007, it established the regulations for the official university education. The
      current nursing specialties in Spain include family and community health nursing,
      midwifery, mental health nursing, geriatric nursing, health work nursing, medical
      care nursing and pediatric nursing. This new nursing education structure is
      expected to improve health care as well as nursing reliability and autonomy.

PMID- 19111943
TI  - MoCRZ1, a gene encoding a calcineurin-responsive transcription factor, regulates
      fungal growth and pathogenicity of Magnaporthe oryzae.
AB  - Ca(2+)-dependent signaling plays important roles in cellular development and
      metabolism in fungi. Pharmacological and molecular evidence clearly indicates
      that Ca(2+)-dependent signaling is required for infection-related development and
      pathogenicity in the rice blast fungus Magnaporthe oryzae. However, little
      information is available on downstream regulators in the Ca(2+)-dependent
      signaling pathway. To understand the role of a calcineurin-dependent
      transcription factor in the rice blast fungus, an ortholog of Saccharomyces
      cerevisiae CRZ1 in M. oryzae, MoCRZ1, was identified and functionally
      characterized. The Deltamocrz1 mutant exhibited impaired growth in the presence
      of Ca(2+) ions or cell wall perturbing agents. The Deltamocrz1 mutant also showed
      reduced conidiation and reduced pathogenicity, which is mainly due to a defect in
      host penetration. MoCRZ1 fused to EGFP was trans-localized into the nucleus in a
      Ca(2+)/calcineurin-dependent manner. The MoCRZ1 gene is also required for the
      calcineurin-dependent transcriptional induction of FKS1, a gene encoding a beta
      1,3 glucan synthase, CHS2 and CHS4, genes encoding two chitin synthases, and PMC
      and PMR gene families encoding P-type ATPases in response to Ca(2+). These
      results suggest that MoCRZ1 is a downstream regulator in Ca(2+)-dependent
      signaling for pathogenicity in M. oryzae, and its biochemical mechanisms are well
      conserved among fungal species.

PMID- 19111944
TI  - Efficient layered density-based clustering of categorical data.
AB  - A challenge involved in applying density-based clustering to categorical
      biomedical data is that the "cube" of attribute values has no ordering defined,
      making the search for dense subspaces slow. We propose the HIERDENC algorithm for
      hierarchical density-based clustering of categorical data, and a complementary
      index for searching for dense subspaces efficiently. The HIERDENC index is
      updated when new objects are introduced, such that clustering does not need to be
      repeated on all objects. The updating and cluster retrieval are efficient.
      Comparisons with several other clustering algorithms showed that on large
      datasets HIERDENC achieved better runtime scalability on the number of objects,
      as well as cluster quality. By fast collapsing the bicliques in large networks we
      achieved an edge reduction of as much as 86.5%. HIERDENC is suitable for large
      and quickly growing datasets, since it is independent of object ordering, does
      not require re-clustering when new data emerges, and requires no user-specified
      input parameters.

PMID- 19111946
TI  - Introduction of the displaced and crossover type of mattress suture for hard
      palate closure.

PMID- 19111945
TI  - Orofacial tumours and tumour-like lesions in Ghana: a 6-year prospective study.
AB  - A total of 182 patients with orofacial tumours and tumour-like lesions who
      attended the oral and maxillofacial surgical department of the Korle-Bu Teaching
      Hospital, Accra, were studied from 1 January 1998 to 31 December 2003. Both
      malignant and benign tumours were recorded and were more common among men
      (99/182, 54%) in whom they were seen most often between the ages of 41 and 70
      years. Among female patients they were more common in the 11-20 year age group.
      The mandible, maxilla, and palate were most often affected. A total of 108
      tumours were diagnosed as malignant (59%), 27 (15%) as benign odontogenic
      tumours, and 47 (26%) as benign non-odontogenic and tumour-like lesions.
      Malignant tumours were usually detected in men between the ages of 41 and 70
      years (43% of all men); whilst benign tumours were evenly distributed between the
      sexes with more among girls in the 11-20 year age group. The most common
      malignant tumours were squamous cell carcinoma (SCC), (69/108, 64%) and lymphomas
      (18/108, 17%). The predominant benign odontogenic and non-odontogenic tumours
      were ameloblastoma and fibro-osseous lesions, respectively. The usual method of
      treatment was resection (58/182, 32%).

PMID- 19111947
TI  - Utility of positron emission tomography/computed tomography in the detection of
      malignancy within a choledochal cyst.

PMID- 19111948
TI  - Gastrointestinal stromal tumor causing obscure-occult gastrointestinal bleeding.

PMID- 19111949
TI  - A systematic review of the definitions, prevalence, and response to treatment of
      nocturnal gastroesophageal reflux disease.
AB  - BACKGROUND & AIMS: More than half of patients with chronic gastroesophageal
      reflux (GERD) report nocturnal symptoms. We performed systematic literature
      review to define nocturnal heartburn and to determine potential causality between
      nocturnal reflux and extraesophageal manifestations. METHODS: We performed a
      search of literature published from 1974-2007. Each study was examined by 2
      reviewers and rated on the basis of study type and outcome. RESULTS: Screening of
      445 trials identified 59 (13%) studies relevant for analysis. Twenty-two (5%) of
      the trials described potential changes in sleep parameters resulting from
      treatment of heartburn. In most studies, nocturnal reflux was defined as
      heartburn symptoms that impacted sleep quality and duration. On the basis of 5
      large population studies, the mean +/- standard deviation prevalence of nocturnal
      heartburn was 54% +/- 22%. Consequences of nocturnal reflux included poor sleep
      quality, daytime fatigue, difficulty initiating sleep or arousals from sleep, and
      impaired work productivity. The strength of the association between the
      occurrence of nocturnal reflux and late evening meals was flawed as a result of
      the confounding effect of the evening meal content. There was no evidence
      supporting causality between nocturnal heartburn and asthma or obstructive sleep
      apnea. Subjective, but not objective, measures of sleep improved with antireflux
      therapy. Head of bed elevation, proton pump inhibitor therapy, H(2)-receptor
      antagonists, and Nissen fundoplication alleviated nocturnal heartburn and
      associated sleep disturbances. CONCLUSIONS: Nocturnal GERD is common and is
      associated with adverse sleep parameters. It can be effectively managed with
      medical and surgical therapy.

PMID- 19111950
TI  - Loading along the lumbar spine as influence by speed, control, load magnitude,
      and handle height during pushing.
AB  - BACKGROUND: Low back loading and risk associated with pushing activities have
      been poorly understood. Previous studies have demonstrated that increases in
      anterior/posterior shear forces are primarily initiated by antagonistic
      coactivity within the torso. Yet, few studies have considered the range of
      activities that might contribute to the antagonistic coactivation and subsequent
      spine loading. METHODS: Twenty subjects were tested to examine how various
      physical factors might influence spine loads during pushing tasks that workers
      might experience in industrial settings. Load magnitude, speed of push, required
      control, and handle height were varied while pushing both carts and overhead
      suspended loads. A biologically-assisted biomechanical model was used to assess
      compression, anterior/posterior shear, and lateral shear over the various levels
      of the lumbar spine. FINDINGS: Anterior/posterior shear loads were greatest at
      the upper levels of the lumbar spine and of a magnitude that would be of concern.
      Anterior/posterior shear was influenced by all experimental factors to varying
      degrees except for the nature of the load (cart vs. suspended). INTERPRETATION:
      This study confirms the notion that pushing and pulling is not as simple a task
      as once believed since it entails a complex biomechanical activity. Spine shear
      forces result from a complex coactivation of trunk muscle activities and spine
      orientations that are influenced by several occupational factors. This study may
      help explain why low back pain rates in some work environments associated with
      lifting may not be reduced even when lifting interventions (that change the task
      from lifting to pushing) are employed.

PMID- 19111951
TI  - Embryonic expression of Drosophila IMP in the developing CNS and PNS.
AB  - Drosophila IMP (dIMP) is related to the vertebrate RNA-binding proteins IMP1-3,
      ZBP1, Vg1RBP and CRD-BP, which are involved in RNA regulatory processes such as
      translational repression, localization and stabilization. The proteins are
      expressed in many fetal tissues, including the developing nervous system, and IMP
      up-regulation in solid tumors correlates with a high metastatic potential and
      poor prognosis. In this study, we used immunohistochemistry and live-imaging of
      an endogenous promoter-driven GFP-dIMP fusion protein to reveal the expression
      pattern of dIMP protein throughout embryogenesis. In the cellular blastoderm,
      immunoreactivity was seen in the entire cell-layer, where it was localized
      apically to the nucleus, and in the pole cells. Later, the GFP-dIMP fusion
      protein appeared in the developing central nervous system, both in the brain and
      in the ventral nerve cord. In the peripheral nervous system, immunoreactivity was
      detected in both neurons and accessory cells of chordotonal and external sensory
      organs.

PMID- 19111952
TI  - "HIV is irrelevant to our company": everyday practices and the logic of
      relationships in HIV/AIDS management by Japanese multinational corporations in
      northern Thailand.
AB  - Multinational corporations (MNCs) are important participants in workplace
      initiatives on HIV/AIDS as they collaborate with international organizations to
      globally promote various policies and guidelines. To date, MNCs have enacted the
      majority of such initiatives in North America, Europe and South Africa, but we
      have little information on how MNCs elsewhere, especially in Japan, have
      responded to the issue of HIV/AIDS in the workplace. This study examines the
      actual on the ground situation of HIV/AIDS management in Japanese MNCs,
      specifically investigating everyday corporate practices in the context of
      internal interactions and relationships and the resulting practices and outlook
      concerning HIV/AIDS. It is based on a secondary analysis of ethnographic case
      studies conducted in 10 Japanese-affiliated companies in northern Thailand.
      Japanese managers, Thai managers and ordinary Thai workers all considered
      HIV/AIDS to be "irrelevant" to their company and/or themselves. HIV/AIDS measures
      in the companies were limited to provision of information. This perception and
      management of HIV/AIDS developed from their everyday interactions governed by the
      logic of relationships in the companies. In these interactions, they categorized
      others based on their ascriptive status, primarily based on class, ethnicity and
      nationality. They sought scapegoat groups that were lower than them in the class-
      and ethnicity/nationality-based hierarchical system, and cast the risk of HIV
      infection upon the scapegoat groups, thus reducing their own sense of risk. The
      paper shows that the relational logic, not ideals or principles, influences their
      views of and actions concerning HIV/AIDS management in the companies. This is why
      Japanese companies are unable to deal with HIV/AIDS in terms of international
      policies and guidelines that are based on the logic of human rights and the logic
      of business principles. The results suggest a need for international policymakers
      to pay more attention to everyday practices in the actual field of policy
      dissemination.

PMID- 19111953
TI  - Mass spectrometric demonstration of the presence of liver carnitine
      palmitoyltransferase-I (CPT-I) in heart mitochondria of adult rats.
AB  - The carnitine palmitoyltransferase-I (CPT-I) enzymes catalyze the regulated step
      in overall mitochondrial fatty acid oxidation. The liver and muscle isoforms are
      expressed in liver and skeletal muscle respectively with the isoforms exhibiting
      different kinetic properties and apparent molecular weight masses. In contrast,
      the heart expresses both isoforms at the mRNA level. However, for the expression
      of the liver isoform at the protein level only indirect evidence is available,
      such as tagging with radiolabeled CPT-I inhibitors followed by SDS-PAGE
      separation and kinetic analysis using inhibitors. The importance of fatty acid
      oxidation in the heart and the potential regulation via the liver isoform of CPT
      I demands proof of the liver isoform in the heart. Using a proteomic approach in
      the present study we demonstrate that rat heart mitochondria (a) contain both the
      muscle and liver isoforms; (b) both proteins retain their C- and N-termini; (c)
      the N-terminal alanine residues are acetylated; (d) and in rat heart mitochondria
      the liver isoform is phosphorylated on tyrosine 281. By providing amino acid
      sequence information this is the first unequivocal demonstration that the liver
      isoform of CPT-I is expressed at the protein level in adult rat heart
      mitochondria and that the apparent smaller molecular size of the muscle isoform
      is not due to proteolytic truncation.

PMID- 19111954
TI  - Solubilization methods and reference 2-DE map of cow milk fat globules.
AB  - Milk fat globules (MFGs) are secretory vesicles assembled and secreted by mammary
      epithelial cells during lactation. They consist of fat globules surrounded by a
      lipid bilayer membrane which is derived from the apical membrane of the lactating
      cells. MFGs contain, besides lipids, proteins from the apical plasma membrane and
      from the cytoplasmatic material. Their peculiar vesicle nature makes them a
      suitable and easily available source of biological material in monitoring the
      physiopathological state of the mammary gland. Unfortunately, the conspicuous
      lipidic component of MFGs consistently limits protein extraction and purification
      for MFG proteomic investigations. This work deals with the development of a
      suitable procedure for protein extraction from the cow MFGs in order to
      qualitatively and quantitatively improve 2-D electropherograms of the MFG. MFGs
      were purified from raw milk by centrifugation and then delipidated/precipitated.
      The resulting protein pellets were solubilised using four different 2-D SDS PAGE
      compatible lysis buffers. Applied methodological procedures for protein
      extraction and evaluation of the resulting 2-D protein-pattern are presented and
      discussed. Using these procedures a reference 2-D map of cow milk fat globules is
      also reported. The majority of the obtained identifications was represented by
      proteins involved in lipid synthesis or in fat globule secretion.

PMID- 19111955
TI  - Standardized peptidome profiling of human cerebrospinal fluid by magnetic bead
      separation and matrix-assisted laser desorption/ionization time-of-flight mass
      spectrometry.
AB  - Peptidome profiling of human cerebrospinal fluid (CSF) is a promising tool to
      identify novel disease-associated biomarkers. Our aim was to develop a
      standardized protocol for reproducible peptidome profiling of CSF using magnetic
      bead (MB) separation followed by MALDI-TOF MS. Peptidome fractionation and
      profiling of CSF were performed using MBs with different surface functionalities.
      We investigated exogenous variables (storage conditions, freeze-thaw-cycles) and
      endogenous interferences (albumin, immunoglobulin, blood, leukocytes) in pooled
      CSF samples. We detected approximately 500 signals with an S/N ratio >10 and an
      overlap frequency of about 40% in non-pathological CSF. Within- and between-day
      imprecisions in relative signal intensities ranged from 3 to 28% and 7 to 47%,
      respectively. CSF storage at room temperature for up to 6 h and at 4 degrees C
      for up to 3 days did not significantly influence the mass spectra. Consecutive
      freeze-thaw-cycles significantly affected the mass spectra. High albumin and
      immunoglobulin content altered the CSF preparation using MB-HIC C8 beads. Blood
      contamination showed no effect on mass spectra up to a hemoglobin concentration
      of 0.075 micromol/L. The presence of leukocytes up to a cell number of 30 Mpt/L
      did not affect mass spectra. Our reliable pretreatment protocol allows
      standardization of preanalytical modalities and thereby enables reproducible
      peptidome profiling of human CSF using MB separation followed by MALDI-TOF MS.

PMID- 19111957
TI  - Sudden cardiac arrest in a patient taking chloroquine.

PMID- 19111958
TI  - Accidental shock to rescuer from an implantable cardioverter defibrillator.

PMID- 19111959
TI  - Is there any room for shortening hands-off time further when using an AED?
AB  - BACKGROUND: Automated external defibrillators (AEDs) play a very important role
      in out-of-hospital cardiopulmonary resuscitation (CPR). The mandatory hands-off
      time imposed by current AEDs is not short enough to bring about the full benefits
      of rapid defibrillation with an AED into light. The aim of this study is to
      examine whether a change in the process of charging the capacity and removing
      explanations from the prompts of the AEDs shortens hands-off time. METHODS: The
      operating steps and the voice prompts of the current AEDs were reviewed and the
      time intervals between the steps and the voice prompts were measured. We modified
      an AED to fully precharge the capacitor and to contain more concise voice
      prompts. RESULTS: We had 42 expert rescuers and 50 lay-person rescuers perform 2
      rescuer CPR with the modified AED and the old AED, respectively. Using the
      modified AED significantly reduced hands-off times by 9.95 s (95% CI: 9.67-10.23)
      in 2-rescuer CPR and by 10.68 s (95% CI: 9.75-11.61) in 1-rescuer CPR (p<0.001).
      CONCLUSION: Full precharging of the capacitor and exclusion of explanations from
      the voice prompts of AEDs can shorten the hands-off time in both 1 and 2-rescuer
      CPR.

PMID- 19111960
TI  - Lateral tilt position for obese patients.

PMID- 19111961
TI  - Computer tomography showing left coronary artery occlusion in a patient having
      manual chest compressions.

PMID- 19111962
TI  - Flexible interval mixed-integer bi-infinite programming for environmental systems
      management under uncertainty.
AB  - A number of inexact programming methods have been developed for municipal solid
      waste management under uncertainty. However, most of them do not allow the
      parameters in the objective and constraints of a programming problem to be
      functional intervals (i.e., the lower and upper bounds of the intervals are
      functions of impact factors). In this study, a flexible interval mixed-integer bi
      infinite programming (FIMIBIP) method is developed in response to the above
      concern. A case study is also conducted; the solutions are then compared with
      those obtained from interval mixed-integer bi-infinite programming (IMIBIP) and
      fuzzy interval mixed-integer programming (FIMIP) methods. It is indicated that
      the solutions through FIMIBIP can provide decision support for cost-effectively
      diverting municipal solid waste, and for sizing, timing and siting the
      facilities' expansion during the entire planning horizon. These schemes are more
      flexible than those identified through IMIBIP since the tolerance intervals are
      introduced to measure the level of constraints satisfaction. The FIMIBIP schemes
      may also be robust since the solutions are "globally-optimal" under all scenarios
      caused by the fluctuation of gas/energy prices, while the conventional ones are
      merely "locally-optimal" under a certain scenario.

PMID- 19111963
TI  - Potential utilization of riverbed sediments by hydrothermal solidification and
      its hardening mechanism.
AB  - Hydrothermal solidification of riverbed sediments (silt) has been carried out in
      a Teflon (PTFE) lined stainless steel hydrothermal apparatus, under saturated
      steam pressure at 343-473 K for 2-24 h by calcium hydrate introduction.
      Tobermorite was shown to be the most important strength-producing constituent of
      the solidified silt. A longer curing time or a higher curing temperature was
      shown to be favorable to the tobermorite formation, thus promoting strength
      development; however, overlong curing time (24 h) seemed to affect the strength
      development negatively. The hardening mechanism consisted of the crystal
      growth/morphology evolution during the hydrothermal process. The species
      dissolved from the silt were precipitated first as fine particles, and then some
      of the particles seemed to build up the rudimental morphology of calcium silicate
      hydrate (CSH) gel. The CSH gel, with precipitated particles, appeared to cause
      some reorganization within the matrix, which made the matrix denser and thus gave
      an initial strength development. Tobermorite, transformed inevitably from the CSH
      gel, reinforced the matrix with its interlocked structure, and thus further
      promoted the strength development.

PMID- 19111964
TI  - Spatial and temporal variations in NO(2) distributions over Beijing, China
      measured by imaging differential optical absorption spectroscopy.
AB  - During the CAREBEIJING campaign in 2006, imaging differential optical absorption
      spectroscopy (I-DOAS) measurements were made from 08:00 to 16:00 on September 9
      and 10 over Beijing, China. Detailed images of the near-surface NO(2)
      differential slant column density (DSCD) distribution over Beijing were obtained.
      Images with less than a 30-min temporal resolution showed both horizontal and
      vertical variations in NO(2) distributions. For DSCD to mixing ratio conversion,
      path length along the lines of I-DOAS lines of sight was estimated using the
      light-extinction coefficient and Angstrom exponent data obtained by a
      transmissometer and a sunphotometer, respectively. Mixing ratios measured by an
      in-situ NO(2) analyzer were compared with those estimated by the I-DOAS
      instrument. The obtained temporal and spatial variations in NO(2) distributions
      measured by I-DOAS for the two days are interpreted with consideration of the
      locations of the major NO(x) sources and local wind conditions. I-DOAS
      measurements have been applied in this study for estimating NO(2) distribution
      over an urban area with multiple and distributed emission sources. Results are
      obtained for estimated temporal and spatial NO(2) distributions over the urban
      atmosphere; demonstrating the capability of the I-DOAS technique. We discuss in
      this paper the use of I-DOAS measurements to estimate the NO(2) distribution over
      an urban area with multiple distributed emission sources.

PMID- 19111965
TI  - Mountain substitutability and peak load pricing of high alpine peaks as a
      management tool to reduce environmental damage: a contingent valuation study.
AB  - High alpine peaks throughout the world are under increasing environmental
      pressure from hikers, trekkers, and climbers. Colorado's "Fourteeners", peaks
      with summits above 14,000 feet are no exception. Most of these peaks have no
      entrance fees, and reach ecological and social carrying capacity on weekends.
      This paper illustrates how a series of dichotomous choice contingent valuation
      questions can be used to evaluate substitutability between different alpine peaks
      and quantify the price responsiveness to an entrance fee. Using this approach, we
      find that peak load pricing would decrease use of popular Fourteeners in Colorado
      by 22%. This reduction is due almost entirely to substitution, rather than income
      effects. There is also price inelastic demand, as 60% of the hikers find no
      substitution for their specific Fourteener at the varying cost increases posed in
      the survey. The no substitute group has a mean net benefit of $294 per hiker, per
      trip, considerably higher than visitor net benefits in most recreational use
      studies.

PMID- 19111966
TI  - Linking birds, fields and farmers.
AB  - The dramatic decline in the presence of farmland birds during recent decades has
      provoked much attention in agri-environmental policy and ecological research.
      However, the still limited understanding of the socio-economical mechanisms that
      govern the decline in bird presence hampers the formulation of effective
      adjustments in land-use and farming practices that could support the return of
      birds to farmland, i.e. the required fine-tuning of management practices. As a
      consequence, the existing agri-environmental schemes that offer financial
      compensation to farmers for implementing generally simple and rather crude
      measures to stimulate the presence of birds have been limited in their
      effectiveness and subject to much debate. The objective of this paper is to
      provide a sociological appraisal of farmers' experiences with meadow bird
      protection in a mainly dairy farming area in the Netherlands. The methodology
      combined visual map analysis, surveys, interviews with farmers and experts, and
      monitoring farmers' discussions. The results allowed an assessment of (i)
      farmers' views on historical changes in bird numbers in the area and the current
      distribution of bird nests, (ii) locally adjusted, fine-tuned management
      practices that were considered to be promising for protecting bird nests, (iii)
      the importance of farm management with 'an eye for birds', i.e. farmers and/or
      birdwatchers paying additional attention to the presence of nests and chicks
      before carrying out farming activities, and (iv) the views of key experts in the
      socio-institutional network in the case study area. The paper concludes that
      there are various promising options for fine-tuning farm management so it offers
      better bird protection, but it is expected that such measures will predominantly
      be adopted on less intensively managed farms.

PMID- 19111967
TI  - Sorption of dissolved lead from shooting range soils using hydroxyapatite
      amendments synthesized from industrial byproducts as affected by varying pH
      conditions.
AB  - For immobilization technologies to be successful, the use of readily available
      and cost advantageous amendment is important when the remediation targets vast
      amounts of contaminated soils. The objectives of this study were to investigate
      whether the byproduct-synthesized hydroxyapatite can be used as an immobilizing
      amendment for dissolved Pb from a shooting range soil, and to model the kinetic
      data collected from dissolution experiments. A soil-solution kinetic experiment
      was conducted under fixed pH conditions as a function of time. A Pb-contaminated
      soil was reacted with various hydroxyapatite amendments to determine the
      dissolution rate and mineral products of soil Pb. Three types of amendments used
      were pure hydroxyapatite (HA), and poorly crystalline hydroxyapatites synthesized
      from gypsum waste (CHA), and synthesized from incinerated poultry litter (PHA).
      The dissolved Pb concentration decreased with the addition of amendments at pH 3
      7. Both CHA and PHA were more effective than HA for attenuating Pb dissolution at
      pH 6 and above. According to the thermodynamic calculation at pH 6, the dissolved
      Pb concentration for CHA and PHA treatments was predicted to be 66% and 50% lower
      than that of HA treatment, respectively. A better Pb immobilization effect
      demonstrated by CHA and PHA resulted in their greater solubility at higher pH,
      which may promote the formation of chloropyromorphite precipitates. Dissolution
      kinetics of soil Pb was adequately explained by pseudo-first order and pseudo
      second order equations in acid pH ranges. According to the ion exchange model, an
      adequate agreement between the experimental data and regression curves was shown
      in the initial 40 min of the reaction process, but the accuracy of model
      predictability decreased thereafter. According to kinetic models and dissolution
      phenomena, CHA and PHA amendments had better Pb sorption capacity with rapid
      kinetics than pure hydroxyapatite at weak acid to neutral pH.

PMID- 19111968
TI  - Echocardiographic and histological assessment of age-related valvular changes in
      normal rats.
AB  - Aging is associated with morphologic and functional alterations of the rat's left
      ventricle. However, the time-course of valvular function and morphology in normal
      aging rats has not yet been studied. For this purpose, 30 male Wistar rats (318
      +/- 5g, 10 weeks old) underwent serial echocardiograms for 58 weeks under sodium
      pentobarbital 50 mg/kg IP anesthetization followed by necropsy. Histopathology
      was also performed in two additional groups of 10 rats at 10 and 30 weeks of age.
      Regurgitations were considered as any retrograde flow on 2-D or M-mode color
      Doppler echocardiography. Tricuspid regurgitation was already found at 10 weeks
      of age and became more frequent with age. Pulmonary, mitral and aortic
      regurgitation was seldom observed at 10 weeks but became more frequent after 30
      weeks. For the mitral and aortic valve, this was also associated with an increase
      in valvular thickness because of nodular or segmental myxoid leaflet changes. The
      severity of valvular regurgitations did not increase with age. In conclusion,
      aging leads to morphologic and functional valvular changes in normal rats. This
      is important when investigating models of valvular heart disease in small
      animals.

PMID- 19111969
TI  - Quantification of left to right shunt in patent ductus arteriosus by color
      Doppler.
AB  - Ultrasound is a reliable tool to diagnose patent ductus arteriosus in premature
      infants but no reliable noninvasive method exists to quantify ductal flow. The
      aim of this study was to quantify the size of the shunt via persistent ductus
      arteriosus from pixel counts in color Doppler flow images. A cotton band was
      placed around the ductus arteriosus of newborn lambs to adjust the magnitude of
      flow. For flow measurements, ultrasonic transit time flow probes were applied
      around the ascending aorta and ductus arteriosus. Twenty-four different flow
      states were attained in four newborn lambs. An Acuson Sequoia scanner equipped
      with a 7 MHz transducer was used to register Doppler data and images with maximal
      color distribution during diastole in the pulmonary artery longitudinal sections
      (PALS). Each image-pixel was matched with the color velocity bar and the pixels
      were assigned to the corresponding flow velocity. The total area showing color
      relative to the area of the PALS correlated well with the amount of ductal flow
      (r = 0.87, r(2) = 0.75, p < 0.001). When Qp/Qs was >1.4:1, more than 40% of the
      area in PALS in diastole exhibited color information. Similarly, the color pixel
      velocities squared correlated with the size of the shunt. Quantification of the
      percentage of pixels in a color Doppler registration via a computer-based
      analysis shows a high correlation with the size of ductal shunting.

PMID- 19111970
TI  - Changes in B-mode ultrasound echo intensity following injection of bupivacaine
      hydrochloride to rat hind limb muscles in relation to histologic changes.
AB  - This study tested the hypothesis that infiltration of inflammatory cells in
      muscle fibers would increase echo intensity (image brightness) of B-mode
      ultrasound images. Bupivacaine hydrochloride (BPVC) or saline solution (SAL) was
      injected to the tibialis anterior (TA) muscles of 14- to 23-wk-old male Wistar
      rats. Ultrasound images were taken from the muscles before and at 0, 2, 4, 6, 9,
      12, 24, 48, 72, 120, 168 and 336 h after the injection and analyzed for the echo
      intensity (echogenicity) expressed as the mean value of image pixel value of a
      region-of-interest. Changes in the echo intensity were compared between BPVC
      injected and control or SAL-injected muscles. In the subsequent study, rats (n =
      2 per time point) were sacrificed after taking ultrasound image at 0, 2, 6, 12,
      24, 48 and 168 h after BPVC injection to the right TA and SAL injection to the
      left TA to observe histologic changes under a light microscope and the
      relationship between echo intensity and inflammatory cells was assessed. No
      significant changes in echo intensity were observed for the control, but BPVC
      induced significant (p < 0.05) increases in the echo intensity peaking 0 to 24 h
      postinjection. SAL also increased echo intensity immediately after injection but
      returned to the baseline by 24 h postinjection. The time course of changes in the
      echo intensity did not match with the time course of increases in inflammatory
      cells in the muscle. It is concluded that infiltration of inflammatory cells is
      not a direct cause of the increased echo intensity.

PMID- 19111971
TI  - Imaging of gaps in digital joints by measurement of ultrasound transmission using
      a linear array.
AB  - In orthodontic dentistry for young subjects, it is important to assess the degree
      of growth of the jaw bones to determine the optimum time for treatment. The
      structure of the digital joint changes with age, with such changes correlating to
      the degree of bone growth (including jaw bones). There are two gaps in the
      digital joint of a young subject, one of which disappears with aging. In the
      present study, a method for noninvasive assessment of such change in the
      structure of a digital joint was examined, in which continuous-wave ultrasound is
      radiated to a digital joint by a single-element ultrasonic transducer. This
      continuous ultrasound, which passes through the digital joint, is received by a
      linear array ultrasonic probe situated opposite the transducer. The probe
      simultaneously realizes pulse-echo imaging and imaging of transmission
      ultrasound, which passes through the joint. Using this experimental apparatus,
      the existence and position of a gap can be detected clearly by imaging the
      transmission ultrasound on a pulse-echo image. In basic experiments, continuous
      wave ultrasound generated by a planar or focused transducer was radiated to a gap
      between two acrylic bars, which simulated that in a digital joint; transmission
      ultrasound, which passed through the gap, was measured with a linear array probe.
      The basic experimental results showed that a gap with a width >0.4 mm is
      detectable and that the width at half maximum of the amplitude profile of the
      received transmission ultrasound that passed through the gap correlated with the
      width of the gap. Furthermore, in the preliminary in vivo experiments,
      transmission ultrasound that passed through two gaps in the case of a child was
      clearly imaged by the proposed method, and that which passed through only one gap
      in the case of an adult was also imaged. These results show the possibility for
      the use of the proposed method to noninvasively assess the change in the
      structure of a joint as a result of aging.

PMID- 19111972
TI  - Transthoracic ultrasound in the evaluation of pulmonary fibrosis: our experience.
AB  - The purpose of this study was to identify the ultrasonographic features of mild,
      moderate and severe pulmonary fibrosis. Between December 2005 and November 2007,
      transthoracic ultrasonography (US) was performed by a single operator with
      specific training in lung sonography on 84 consecutive patients (51 males and 33
      females, aged 46 to 73 y) with pulmonary fibrosis. The obtained data were
      compared with those from a sample of 162 healthy subjects (78 men and 84 women,
      aged 18 to 76 y). The disease was idiopathic (biopsy confirmed) in 53/84 cases
      (63%). In the remaining (all histologically confirmed) cases, it was associated
      with systemic sclerosis (n = 18), rheumatoid arthritis (n = 4), mixed connective
      tissue disease (n = 4), Sjogren syndrome (n = 4), polymyositis (n = 2) or primary
      biliary cirrhosis (n = 1). Disease severity was classified as mild, moderate or
      severe based on clinical findings and the results of standard chest radiography,
      high-resolution computed tomography and pulmonary function tests. Pulmonary
      fibrosis was associated with the following US findings: (1) fragmented, irregular
      thickening (micro3 mm) of the "pleural line" distributed over the whole surface
      of the lung, especially in the lower posterior lobe (observed in all 84
      patients); (2) subpleural cysts (seen in 57/84 (68%) cases of moderate-severe
      disease); (3) reduction or absence of the physiological "gliding sign" related to
      disease severity (observed in 33/84 to 39% cases); and (4) increased number of
      horizontal (and to a lesser extent vertical) reverberation artifacts (seen in 41
      patients with advanced fibrosis, 34% of the total series). All abnormalities were
      detected in both lungs. Although lung biopsy is still the gold standard for
      diagnosis of interstitial lung disease, transthoracic ultrasound can document
      early and late-stage changes associated with this disease.

PMID- 19111973
TI  - Evolution of 3-D power Doppler indices of fetal brain in normal pregnancy.
AB  - We assessed the vascular indices of the anterior territory of the middle cerebral
      artery (MCA) in normal pregnancies using 3-D power Doppler (3DPD). A cross
      sectional study was carried out on 90 normal pregnancies between 24 and 35 weeks.
      All examinations were performed by a single operator using a volumetric
      transducer. The anterior territory of the MCA was scanned and the volumes were
      captured using 3DPD. The sphere mode of the VOCAL program was used to calculate
      the following vascular indices: vascularization index (VI), flow index (FI) and
      vascularization and flow index (VFI). Models of polynomial regression and
      Pearson's correlation coefficient were used to evaluate the correlation between
      gestational age (GA) and the vascular indices. The 3DPD vascular indices had a
      low correlation with gestational age (VI - r = 0.324, p = 0.002; FI - r = 0.375,
      p < 0.001; VFI - r = 0.374, p < 0.001). There was a low correlation between GA
      and the 3DPD vascular indices of the anterior territory of the MCA.

PMID- 19111974
TI  - Fabrication and photocatalytic property of Pt-intercalated layered perovskite
      niobates H(1-x)LaNb(2-x)Mo(x)O(7) (x=0-0.15).
AB  - H(1-x)LaNb(2-x)Mo(x)O(7) was prepared by solid-state reaction followed by an ion
      exchange reaction. Pt was incorporated in the interlayer of H(1-x)LaNb(2
      x)Mo(x)O(7) by the stepwise intercalation reaction. The H(1-x)LaNb(2-x)Mo(x)O(7)
      showed hydrogen production activity and the activities were greatly enhanced by
      Pt co-incorporating. The x value in H(1-x)LaNb(2-x)Mo(x)O(7) had an important
      effect on the photocatalytic activity of the catalyst. When the x=0.05, the H(1
      x)LaNb(2-x)Mo(x)O(7)/Pt showed a photocatalytic activity of 80 cm(3)h(-1)g(-1)
      hydrogen evolution rate in 10 vol.% methanol solution under irradiation from a
      100 W mercury lamp at 333K.

PMID- 19111975
TI  - Nitrate removal from aqueous solutions by cross-linked chitosan beads conditioned
      with sodium bisulfate.
AB  - The investigation of adsorption of nitrate onto chitosan beads modified by cross
      linking with epichlorohydrin (ECH) and surface conditioning with sodium bisulfate
      was performed. The results indicated that both cross-linking and conditioning
      increased adsorption capacity compared to normal chitosan beads. The maximum
      adsorption capacity was found at a cross-linking ratio of 0.4 and conditioning
      concentration of 0.1mM NaHSO(4). The maximum adsorption capacity was 104.0 mg g(
      1) for the conditioned cross-linked chitosan beads at pH 5, while it was 90.7 mg
      g(-1) for normal chitosan beads. The Langmuir isotherm model fit the equilibrium
      data better than the Freundlich model. The mean adsorption energies obtained from
      the Dubinin-Radushkevich isotherm model for all adsorption systems were in the
      range of 9.55-9.71 kJ mol(-1), indicating that physical electrostatic force was
      potentially involved in the adsorption process.

PMID- 19111976
TI  - An investigation on mechanism of acid drain in heap leaching structures.
AB  - Gravelly drainage layer and semi-slotted polyethylene pipes are two main
      components of drainage system of heap leaching structures. Fluid is locally
      drained and directed to semi-slotted polyethylene pipes by gravelly drainage
      layer. Then, it is sent to a pregnant leach solution (PLS) pond by the semi
      slotted polyethylene pipes gravitationally. In this paper, initially the existing
      relations, suggested for the design of drainage system of heap leaching
      structures, are analyzed. Then, the main differences between fluid drain in
      landfills and heap leaching structures are presented, and consequently, two new
      correction factors, named "replacement" and "delay" factors are suggested. The
      replacement factor illustrates the ratio of mean value of heap layers area to the
      acid-washed area and the delay factor represents the reduction of heap layers
      area. The new correction factors are added to Giroud equation and the modified
      format of the equation is suggested for computing gravelly drainage layer
      thickness of heap leaching structures. Also, these two correction factors are
      added to Majdi et al. equation and two new relations are suggested for
      determination of main and auxiliary drainage semi-slotted polyethylene pipes
      diameters in these structures. Finally, based on the new relations, adequate
      drainage systems are designed for two case studies ("Tarom" and "Sarcheshmeh 2"
      heap leaching structures) and the results are compared with those calculated by
      the exiting equations.

PMID- 19111977
TI  - Interactions of NO2 with activated carbons modified with cerium, lanthanum and
      sodium chlorides.
AB  - Highly porous wood-based activated carbon was impregnated with cerium, lanthanum
      and sodium chlorides using incipient impregnation method. On the samples prepared
      adsorption of NO(2) was carried out from moist (70% humidity) air either with or
      without the prehumidification. The materials were characterized using adsorption
      of nitrogen, thermal analysis, FTIR, and potentiometric titration. The results
      indicated that for all materials a significant amount of NO(2) was reduced to NO
      and released from the system. In the case of virgin carbons, the NO(2)
      interacting with the surface along with nitric and nitrous acids formed there in
      the presence of water significantly increased the acidity of the carbons by the
      formation of oxygen-containing groups and organic nitrates. On the other hand,
      when chlorides were present the capacity to interact with nitrogen dioxide
      increased since the inorganic phase, depending on the nature of metal, bound
      NO(2) in the forms of nitrates (Ce, La, Na), got oxidized/oxidized carbon surface
      (for Ce) or contributed to the formation of nitrosyl chloride (for Na).

PMID- 19111978
TI  - Investigation of a basic dye removal from aqueous solution onto chemically
      modified Unye bentonite.
AB  - The adsorption behavior of crystal violet (CV(+)) from aqueous solution onto
      magnesium-oxide coated bentonite (MCB) sample was investigated as a function of
      parameters such as initial CV(+) concentration, contact time and temperature. The
      Langmuir, and Freundlich adsorption models were applied to describe the
      equilibrium isotherms. The Langmuir monolayer adsorption capacity of MCB were
      estimated as 496 mg/g. The pseudo-first-order, pseudo-second-order kinetic and
      the intra-particle diffusion models were used to describe the kinetic data and
      rate constants were evaluated. The values of the energy (E(a)), enthalpy (Delta
      H(not equal)) and entropy of activation (DeltaS(not equal)) were 56.45 kJ/mol,
      53.90 kJ/mol and -117.26 J/mol K, respectively, at pH 6.5.

PMID- 19111979
TI  - Solubility-enhanced electrokinetic movement of hexachlorobenzene in sediments: a
      comparison of cosolvent and cyclodextrin.
AB  - Though solubility-enhanced electrokinetics (EK) has been investigated in
      remediation of soils contaminated with hydrophobic organic chemicals (HOCs), few
      comparative studies were performed regarding the effect of varied solubilizing
      agents on both EK parameters and contaminant removal. In this study, performances
      of two solubilizing agents, ethanol and methyl-beta-cyclodextrin (MCD), were
      compared in terms of either EK parameters or enhancement of hexachlorobenzene
      (HCB) movement in real contaminated sediments. Six bench-scale EK tests were
      conducted under a voltage gradient of 2V cm(-1) for 14 or 21 d. Results reveal
      that ethanol had a more negative effect on cumulative electroosmotic flow (EOF)
      than MCD. Furthermore, the distribution of ethanol in the sediment upon the
      completion of EK tests was lower than that of MCD. The movement of HCB in
      sediments was observed to increase with increasing concentrations of ethanol or
      MCD. Test with 50% ethanol exhibited the highest performance, followed by test
      with 50 g L(-1) MCD. The different performance of HCB removal for tests with
      varied solubilizing agents was found to be a combined effect of the distribution
      of solubilizing agents in sediments, the dissolution of HCB by pore liquid and
      the quantity of cumulative EOF. Finally, an integrated consideration of both EK
      parameters and contaminant removal suggests that MCD can perform better than
      ethanol for a long-term field application.

PMID- 19111980
TI  - Determination of Orange II in food samples after cloud point extraction using
      mixed micelles.
AB  - In this paper, a cloud point extraction method for the determination of trace
      amounts of Orange II by spectrophotometry is described. The method is based on
      the extraction of Orange II from aqueous solution using mixed micelles of non
      ionic surfactant, Triton X-100 and cationic surfactant cetyltrimethyl ammonium
      bromide (CTAB) in acidic media. The extracted surfactant rich phase is diluted
      with water and its absorbance is measured at 484 nm by a spectrophotometer. The
      effects of surfactant, acid and salt concentration, incubation time and
      temperature were investigated. The calibration graph was linear in the range of
      2.1-420 ng mL(-1) of Orange II in the initial solution with r=0.9991 (n=12).
      Detection limit based on three times the standard deviation of the blank (3S(b))
      was 0.67 ng mL(-1) and the relative standard deviation (RSD) for 35 and 105 ng
      mL(-1) of Orange II was 1.20% and 1.49% (n=10), respectively. The method was
      applied to the determination of Orange II in different food samples.

PMID- 19111981
TI  - Revealing interactive toxicity of aromatic amines to azo dye decolorizer
      Aeromonas hydrophila.
AB  - This study attempted to combine chemostat pulse technique (CPT) and dose
      mortality assessment in pursuit of quantitative rankings of toxicity of model
      aromatic amines (MAAs) in the presence of diazo dye reactive red 141 (or Evercion
      Red H-E7B; RR141) upon Aeromonas hydrophila. As known, bacterial decolorization
      performance of azo dyes is directly dependent upon both the characteristics of
      biochemical reactivity and biotoxicity of dyes and related aromatic amines
      towards color removal. Thus, the findings herein indicated that the relative
      toxicity series of MAAs were (1) ortho>para>MAA-free control>meta position (for
      isomeric aminophenols); (2) -OH>-SO(3)H>MAA-free control (-NH(2) at ortho
      position); (3) -COOH>MAA-free control>-OH (-NH(2) at meta position) through the
      CPT at 200mg/L MAAs. Comparison on results in higher levels of MAAs at 1000 mg/L
      almost showed parallel relative toxicity rankings at 200mg/L. Quantification
      using traditional plate count method also confirmed nearly similar trends for
      corresponding MAAs except 3-aminophenol, revealing the promising feasibility of
      CPT for the toxicity assessment in practical applications. In addition, dose
      mortality analysis regularly used in toxicology was used to quantitatively
      determine toxicity rankings of MAAs. In conclusion, this study directly provided
      a kinetic model to quantify the relative toxicity ranking of MAAs in the presence
      of RR141. It could provide a feasible guideline for assessment on the toxicity or
      treatability of azo dyes and MAAs to A. hydrophila in wastewater treatment.

PMID- 19111982
TI  - Conventional hydrothermal synthesis of Na-A zeolite from cupola slag and aluminum
      sludge.
AB  - Na-A type zeolites were prepared from two industrial wastes: the solid by-product
      of cupola slag and aluminum sludge from an aluminum plating plant. Two
      preparation methods using the same starting material compositions were carried
      out. In the first method, alkaline fusion was introduced, followed by the
      hydrothermal treatment to obtain sodium aluminosilicate which was then
      crystallized in NaOH solution under the condition of 90+/-3 degrees C for 1-9h
      with different H(2)O/SiO2 ratios. The result shows that higher H(2)O/SiO2 ratio
      increases the rate of crystallization. The largest amount of crystallinity for Na
      A was found at 3h. In the second method, alkaline hydrothermal treatment without
      fusion was carried out in the same condition as the first method. No Na-A zeolite
      was obtained by this method. The changes of the dissolved amounts of Si(4+) and
      Al(3+) in 3M NaOH were investigated during the hydrothermal reaction.

PMID- 19111983
TI  - Nitrate removal in a closed marine system through the ion exchange membrane
      bioreactor.
AB  - The accumulation of nitrate in closed marine systems presents a problem for both
      the marine life and the environment. The present study, proposes the application
      of the ion exchange membrane bioreactor (IEMB) concept for removing nitrate from
      marine systems, such as aquaculture tanks or marine aquariums. The results
      obtained demonstrate that the IEMB was able to remove naturally accumulated
      nitrate from water taken from a public marine aquarium (Oceanario de Lisboa) and
      bioconvert it, in an isolated compartment (biocompartment), to molecular
      nitrogen, thus preventing secondary contamination of the treated water by
      microbial cells, metabolic by-products and excess of carbon source (ethanol).
      This system allowed for the removal of nitrate at concentrations of 251 and 380
      mg/l down to below 27 mg/l exchanging it for chloride. Under the studied
      operating conditions, the IEMB proves to be a selective nitrate removing
      technology preserving the initial water composition with respect to cations, due
      to the Donnan exclusion effect from the membrane, and minimizing the counter
      diffusion of anions other than nitrate and chloride, due to the use of water with
      the same ionic composition in the biocompartment. This is an advantage of the
      IEMB concept, since the quality of the water produced would allow for the
      reutilisation of the treated water in the aquarium, thereby reducing both the
      wastewater volume and the use of fresh water.

PMID- 19111984
TI  - An algorithm for the kinetics of tire pyrolysis under different heating rates.
AB  - Tires exhibit different kinetic behaviors when pyrolyzed under different heating
      rates. A new algorithm has been developed to investigate pyrolysis behavior of
      scrap tires. The algorithm includes heat and mass transfer equations to account
      for the different extents of thermal lag as the tire is heated at different
      heating rates. The algorithm uses an iterative approach to fit model equations to
      experimental data to obtain quantitative values of kinetic parameters. These
      parameters describe the pyrolysis process well, with good agreement (r(2)>0.96)
      between the model and experimental data when the model is applied to three
      different brands of automobile tires heated under five different heating rates in
      a pure nitrogen atmosphere. The model agrees with other researchers' results that
      frequencies factors increased and time constants decreased with increasing
      heating rates. The model also shows the change in the behavior of individual tire
      components when the heating rates are increased above 30 K min(-1). This result
      indicates that heating rates, rather than temperature, can significantly affect
      pyrolysis reactions. This algorithm is simple in structure and yet accurate in
      describing tire pyrolysis under a wide range of heating rates (10-50 K min(-1)).
      It improves our understanding of the tire pyrolysis process by showing the
      relationship between the heating rate and the many components in a tire that
      depolymerize as parallel reactions.

PMID- 19111985
TI  - Equilibrium, kinetic and thermodynamic studies on the adsorption of 2
      nitroaniline onto activated carbon prepared from cotton stalk fibre.
AB  - Activated carbon prepared from cotton stalk fibre has been utilized as an
      adsorbent for the removal of 2-nitroaniline from aqueous solutions. The influence
      of adsorbent mass, contact time and temperature on the adsorption was
      investigated by conducting a series of batch adsorption experiments. The
      equilibrium data at different temperatures were fitted with the Langmuir,
      Freundlich, Tempkin, Redlich-Peterson and Langmuir-Freundlich models. The
      Langmuir-Freundlich isotherm was found to best describe the experimental data.
      The adsorption amount increased with increasing temperature. The maximum
      adsorption capacity of 2-nitroaniline was found to be 383 mg/g for initial 2
      nitroaniline concentration of 200mg/L at 45 degrees C. The kinetic rates were
      modeled by using the Lagergren-first-order, pseudo-second-order and Elovich
      models. The pseudo-second-order model was found to explain the adsorption
      kinetics most effectively. It was also found that the pore diffusion played an
      important role in the adsorption, and intraparticle diffusion was the rate
      limiting step at the first 30 min for the temperatures of 25, 35 and 45 degrees
      C. FTIR and (13)C NMR study revealed that the amino and isocyanate groups present
      on the surface of the adsorbent were involved in chemical interaction with 2
      nitroaniline. The negative change in free energy (Delta G degrees) and positive
      change in enthalpy (Delta H degrees) indicated that the adsorption was a
      spontaneous and endothermic process.

PMID- 19111986
TI  - Acetate-fed aerobic granular sludge for the degradation of 4-chlorophenol.
AB  - Chlorinated phenols are considered a critical environmental problem, due to their
      extreme toxicity and their widespread use both in industrial and agricultural
      activities. In this study, aerobic granular sludge was initially developed into
      an acetate-fed Granulated Sequencing Batch Reactor (GSBR) and then used for the
      degradation of low chlorinated 4-mono-chlorophenol (4CP), with readily
      biodegradable sodium acetate (NaAc) as co-substrate. Influent 4CP concentration
      ranged between 0 and 50mg/l, with a maximum volumetric organic loading rate of
      0.20 kg(4CP)/m(3)d (0.32 kg(COD-4CP)/m(3)d). Differences in granules shape and
      size were observed with 4CP dosed in the influent at different concentrations,
      and the effects of such toxic compound on acetate removal were evaluated, with
      both unacclimated and acclimated biomass. Aerobic granules grown on acetate as
      carbon source proved to be an interesting solution for the degradation of 4CP,
      showing good resistance to high 4CP concentrations in the influent even if
      unacclimated (short term effects). Moreover, the monitoring of intermediate
      products and the evaluation of chloride release due to 4CP degradation proved
      that acclimated granular sludge could completely remove 4CP (long term effects),
      with high specific removal rates.

PMID- 19111987
TI  - Grass waste: a novel sorbent for the removal of basic dye from aqueous solution.
AB  - The aim of the present work was to investigate the feasibility of grass waste
      (GW) for methylene blue (MB) adsorption. The adsorption of MB on GW material was
      studied as a function of GW dose (0.05-1.20 g), solution pH 3-10, contact time
      and initial concentration (70-380 mg/L). The influence of these parameters on the
      adsorption capacity was studied using the batch process. The experimental data
      were analyzed by the Langmuir and Freundlich isotherms. The adsorption isotherm
      was found to follow the Langmuir model. The monolayer adsorption capacity was
      found to be 457.640 mg/g. The kinetic data were fitted to the pseudo-first-order
      and pseudo-second-order models, and were found to follow closely the pseudo
      second-order kinetic model. The results revealed that GW adsorbent is potentially
      low-cost adsorbent for adsorption of MB.

PMID- 19111988
TI  - Use of maize wastewater for the cultivation of the Pleurotus spp. mushroom and
      optimization of its biological efficiency.
AB  - This study evaluated the Pleurotus spp. mushroom production process using an
      effluent from the maize agroindustrial process as a carbon and nitrogen source
      and as a wetting agent. A complete experimental design based on factorial
      planning was used to optimize the biological efficiency and evaluate the effect
      of the concentration of effluent, pH and species of Pleurotus. The results
      indicated that the effluent affects the biological efficiency for the production
      of both species of mushrooms at all pH values studied. The maximum biological
      efficiency predicted by the model (81.36%) corresponded to the point defined by
      the effluent contents (X(1)=1), pH (X(2)=-1) and fungus species (X(3)=1),
      specifically 50%, 5.0 and P. floridae, respectively. The results demonstrated
      that the effluent is a good alternative for the production of Pleurotus
      mushrooms.

PMID- 19111989
TI  - Pain research from 1975 to 2007: a categorical and bibliometric meta-trend
      analysis of every Research Paper published in the journal, Pain.
AB  - In an attempt to characterize the nature of pain research, every one of the 4525
      Research Papers published in the journal, Pain, from its inception until the end
      of 2007, was examined by a single individual using a consistent set of criteria,
      and was coded for its essential features in four domains: the purpose of the
      study (e.g., characterization of a pain syndrome, evaluation of the role of a
      molecule), the subjects of the study (patients, human "normals", animals), the
      pain states characterized or induced (clinical pain and experimental stimuli),
      and the dependent measures examined (e.g., behaviors, questionnaires, neural
      firing). For papers involving pain patients, the clinical conditions under study
      were coded as well. These categorical data were combined with bibliometric data
      obtained from citation databases. Together, the data allow an examination of 32
      year trends in pain research, and comprise a data compendium fully searchable or
      sortable by any interested individual.

PMID- 19111990
TI  - Echinococcosis in pigs and intestinal infection with Echinococcus spp. in dogs in
      southwestern Lithuania.
AB  - Cystic echinococcosis is a major emerging zoonosis in many Eastern European and
      Asian countries. Post slaughter examinations of 684 pig livers in Lithuania
      revealed significantly higher numbers of Echinococcus granulosus infections in
      animals from family farms (13.2%; 95% CI 10.7-16.2) as compared with those from
      industrial farms (4.1%; 95% CI 0.8-11.5). The prevalence was also significantly
      higher in pigs older than 1 year than in younger ones. In addition, in 0.5% of
      the pigs from the family farms, infertile and calcified E. multilocularis lesions
      were identified by PCR. Faecal samples from rural dogs (n=240) originating from
      177 family farms in 12 villages were investigated for taeniid eggs with two
      methods. Significantly more dogs excreting taeniid eggs were diagnosed with the
      flotation/sieving method (n=34) as compared to the modified McMaster method
      (n=12). Multiplex PCR performed with DNA from taeniid eggs isolated from faeces
      of 34 dogs revealed 26 infections with Taenia spp., 9 with E. granulosus and 2
      with E. multilocularis (4 cases with concurrent Taenia spp. and E. granulosus or
      E. multilocularis infections). Genotyping of E. granulosus cyst tissues from 7
      pigs, 1 head of cattle and from E. granulosus eggs from 8 dog faeces revealed the
      genotype G6/7 ('pig/camel strain') in all cases. The high infection pressure with
      Echinococcus spp. in family farms necessitates initiating control programs.

PMID- 19111991
TI  - Leishmania infantum in a Central Italy dog shelter: retrospective study of
      serologic reactivity during a 4-year period in a confined dog population
      subjected to preventive and therapeutic treatment.
AB  - Leishmaniasis from Leishmania infantum is a parasitary zoonotic disease and a
      serious problem to public health. Guidelines from Italian Health Authority
      (Istituto Superiore di Sanita) suggest to control the zoonotic visceral
      leishmaniasis canine reservoir in endemic areas using an association of
      preventive and therapeutic tools. Moreover, in literature there are no studies
      about the long term effects on the disease seroprevalence and incidence in
      relation to this "holistic" approach. Past research has considered the effects of
      the alternative employment of preventive or therapeutic treatment, usually for
      limited periods. In this retrospective study the patterns of seroprevalence and
      incidence of leishmaniasis in a dog shelter sited in an endemic area of Central
      Italy are described throughout a 4-year period. Both preventive spot-on tools
      (imidacloprid/permetrin) and therapeutic protocols based on antimonials and
      allopurinol were administered. The results showed a progressive reduction of
      prevalence and incidence of serological reactivity to L. infantum, corroborating
      the effectiveness of the treatment administered to the animals. Significant
      improvements from the beginning to the end of the 4-year period were reported,
      considering both prevalence and incidence. A very low rate of relapses (8% in a
      pool of 67 subjects positive since 2004; 10.2% among all subjects enrolled in the
      study) was achieved.

PMID- 19111992
TI  - Newly emerged nulliparous Culicoides imicola Kieffer (Diptera: Ceratopogonidae)
      with pigmented abdomen.
AB  - The method of segregating nulliparous and parous females of Culicoides spp. based
      on the presence of burgundy-red pigment inside the abdominal wall of parous
      Culicoides midges, is used worldwide. Out of 320 females of Culicoides imicola
      trapped by emergence traps, set over an artificial breeding site for 10 and 24
      days, 73 (22.8%) showed a red-pigmentation despite the fact that they were
      nulliparous. This finding indicated that 23% of the "parous" females that are
      examined for the presence of arboviruses and other pathogens or for age-grading
      purposes, are actually old nulliparous females, which had no chance of acquiring
      pathogens. This bias in parous rate distorts upward the calculation of vectorial
      capacity.

PMID- 19111993
TI  - Protection against Toxoplasma gondii brain cyst formation in mice immunized with
      Toxoplasma gondii cytoskeleton proteins and Lactobacillus casei as adjuvant.
AB  - The aim of the study was to evaluate the protection generated in mice against
      Toxoplasma gondii brain cyst burden by vaccination with T. gondii cytoskeleton
      proteins using Lactobacillus casei as adjuvant. One hundred and sixty-eight NIH
      mice were randomly allocated into eight groups of 21 mice each. Animals were
      immunized as follows: in group 1 with Toxoplasma lysate antigen (TLA) in Freund's
      modified adjuvant, containing L. casei (FMA), in group 2 with Toxoplasma
      cytoskeleton proteins (TCPs) in FMA, in group 3 with FMA, in group 4 with
      phosphate buffered saline (PBS), in group 5 with L. casei dead by heath (Lc), in
      group 6 with Freund's complete adjuvant (FCA), in group 7 with TLA in FCA, and in
      group 8 with TCP in FCA. Mean brain cyst burden (+/-S.E.M.) was assessed in mice
      8 weeks after challenge with T. gondii Me49 strain (20 cysts per mouse). The
      percentages of reduction in cyst burden per brain (P<0.01) as compared with the
      group 4 (control: mean 3181+/-97.5) were 77.25% (724+/-98) in group 1, 88.02%
      (381+/-97.5) in group 2, 38.92% (1943+/-130.3) in group 3, 44.31% (1771.4+/-102)
      in group 5, 59.28% (1295.2+/-99.1) in group 7 and 55.69% (1409.5+/-89.9) in group
      8. In order of importance, the best protection was obtained in groups 2, 1, 7, 8,
      5 and 3. Noticeably the mice inoculated with L. casei alone showed a significant
      reduction in T. gondii brain cysts (P<0.01), while those animals treated with FCA
      alone did not. Additionally, IgM anti-T. gondii antibody levels, as determined by
      ELISA 2 weeks after challenge, were highest in group 2 (P<0.01) than in the other
      seven groups. Results suggest that T. gondii cytoskeleton proteins with L. casei
      as adjuvant constitute a good anti-toxoplasmosis vaccine candidate.

PMID- 19111994
TI  - Diagnostic value of rectal temperature of African cattle of variable coat colour
      infected with trypanosomes and tick-borne infections.
AB  - Diagnosis of major endemic bovine parasitic diseases in sub-Saharan Africa such
      as trypanosomosis, theileriosis, anaplasmosis, babesiosis and cowdriosis is
      increasingly relying on clinical diagnosis due to deterioration of veterinary
      services and laboratory facilities. Pyrexia is a common clinical feature of
      aforementioned diseases whose detection relies on measurement of rectal
      temperature. The research undertaken in this study was aimed at assessing the
      effects of diurnal changes and variable coat colour of indigenous Nkedi Zebu
      cattle on the diagnostic value of rectal temperature under tropical conditions.
      The results revealed that variation in rectal temperature was significantly
      influenced by time of day it was taken and by the coat colour of the Nkedi Zebu
      cattle (P<0.001). Rectal temperature experienced diurnal changes: steadily rising
      to reach a peak at 17.00h before declining. The mean rectal temperature of
      unhealthy cattle was significantly higher (P<0.05) than that of the healthy ones
      only between 13.00 and 17.00h of the day. During which period the proportion of
      unhealthy cattle having a rectal temperature of 39.4 degrees C or higher was
      significantly higher than that of healthy ones (P<0.001). Regarding the variable
      coat colour of indigenous breeds, rectal temperature among cattle of different
      coat colours was significantly different (P<0.05). In conclusion it is important
      to consider diurnal changes in rectal temperature and differences due to variable
      coat colour of indigenous African breeds when measuring rectal temperature for
      assessing pyrexia, during clinical diagnosis of bovine trypanosomosis and tick
      borne diseases that are endemic in many countries in sub-Saharan Africa.

PMID- 19111995
TI  - Predicting the effectiveness of virtual reality relaxation on pain and anxiety
      when added to PCA morphine in patients having burns dressings changes.
AB  - BACKGROUND: Pain arising in burns sufferers is often severe and protracted. The
      prospect of a dressing change can heighten existing pain by impacting both
      physically and psychologically. In this trial we examined whether pre-procedural
      virtual reality guided relaxation added to patient controlled analgesia with
      morphine reduced pain severity during awake dressings changes in burns patients.
      METHODS: We conducted a prospective randomized clinical trial in all patients
      with burns necessitating admission to a tertiary burns referral centre. Eligible
      patients requiring awake dressings changes were randomly allocated to single use
      virtual reality relaxation plus intravenous morphine patient controlled analgesia
      (PCA) infusion or to intravenous morphine patient controlled analgesia infusion
      alone. Patients rated their worst pain intensity during the dressing change using
      a visual analogue scale. The primary outcome measure was presence of 30% or
      greater difference in pain intensity ratings between the groups in estimation of
      worst pain during the dressing change. FINDINGS: Of 88 eligible and consenting
      patients having awake dressings changes, 43 were assigned to virtual reality
      relaxation plus intravenous morphine PCA infusion and 43 to morphine PCA infusion
      alone. The group receiving virtual reality relaxation plus morphine PCA infusion
      reported significantly higher pain intensities during the dressing change
      (mean=7.3) compared with patients receiving morphine PCA alone (mean=5.3)
      (p=0.003) (95% CI 0.6-2.8). INTERPRETATION: The addition of virtual reality
      guided relaxation to morphine PCA infusion in burns patients resulted in a
      significant increase in pain experienced during awake dressings changes. In the
      absence of a validated predictor for responsiveness to virtual reality relaxation
      such a therapy cannot be recommended for general use in burns patients having
      awake dressings changes.

PMID- 19111996
TI  - The vital role of transcendental truth in science.
AB  - I have come to believe that science depends for its long-term success on an
      explicit and pervasive pursuit of the ideal of transcendental truth.
      'Transcendental' implies that a value is ideal and ultimate - it is aimed-at but
      can only imperfectly be known, achieved or measured. So, transcendental truth is
      located outside of science; beyond scientific methods, processes and peer
      consensus. Although the ultimate scientific authority of a transcendental value
      of truth was a view held almost universally by the greatest scientists throughout
      recorded history, modern science has all-but banished references to truth from
      professional scientific discourse - these being regarded as wishful, mystical and
      embarrassing at best, and hypocritical or manipulative at worst. With truth
      excluded, the highest remaining evaluation mechanism is 'professional consensus'
      or peer review - beyond which there is no higher court of appeal. Yet in Human
      accomplishment, Murray argues that cultures which foster great achievement need
      transcendental values (truth, beauty and virtue) to be a live presence in the
      culture; such that great artists and thinkers compete to come closer to the
      ideal. So a scientific system including truth as a live presence apparently
      performs better than a system which excludes truth. Transcendental truth
      therefore seems to be real in the pragmatic sense that it makes a difference. To
      restore the primacy of truth to science a necessary step would be to ensure that
      only truth-seekers were recruited to the key scientific positions, and to exclude
      from leadership those who are untruthful or exhibit insufficient devotion to the
      pursuit of truth. In sum, to remain anchored in its proper role, science should
      through 'truth talk' frequently be referencing normal professional practice to
      transcendental truth values. Ultimately, science should be conducted at every
      level, from top to bottom, on the basis of what Bronowski termed the 'habit of
      truth'. Such a situation currently seems remote and fanciful. But within living
      memory, routine truthfulness and truth-seeking were simply facts of scientific
      life - taken for granted among real scientists.

PMID- 19111997
TI  - [Pure rhabdomyosarcoma of the uterine corpus: an exceptional tumor in
      postmenopausal women. Report on two cases].
AB  - Rhabdomyosarcoma (RMS) of the uterine corpus is rare in adult females. This tumor
      can be encountered in two distinct histopathological contexts: usually as a
      component of a malignant mixed mullerian tumor and exceptionally as a pure
      heterologous sarcoma. We report two cases of pure RMS of the uterine corpus
      occurring in postmenopausal women. The two patients suffered from vaginal
      bleeding and preoperative diagnosis was achieved in both cases. Both patients
      benefited from exploratory laparotomy, total hysterectomy and bilateral salpingo
      oophorectomy. Both of them were free from the disease 15 months and 1 year
      respectively, after initial surgery. These two observations are worthy of
      publication because pure RMS of the uterine corpus is exceptional in
      postmenopausal women.

PMID- 19111998
TI  - Paraneoplastic syndromes in patients with nasopharyngeal cancer.
AB  - Paraneoplastic syndromes (PNS) represent the clinical manifestation of the remote
      and indirect effects produced by tumor metabolites or other products.
      Paraneoplastic effects are not directly mediated by tumor invasion of normal
      tissue, or by the disruption of normal function of the involved organ, or by
      distant metastases. More than 260 cases of nasopharyngeal carcinoma (NPC)
      associated with PNS have been reported in the literature. These syndromes can be
      divided into six main groups: cutaneous or dermatologic, endocrine, hematologic,
      osteoarticular or rheumatologic, neurologic, and ocular. The most common
      dermatologic manifestation is dermatomyositis, while the syndrome of
      inappropriate secretion of antidiuretic hormone and occasionally Cushing's
      syndrome due to ectopic ACTH production are the endocrinologic manifestations.
      Tumor fever and leukemoid reaction, osteoarticular or rheumatic syndromes,
      including clubbing of the fingers and toes, sensory neuropathy and demyelinating
      motor polyneuropathy, and rarely optic neuritis represent the most prominent
      examples of the other groups of syndromes. PNS may occur before the NPC is
      manifest, or while it is in an occult stage, and thus the possibility of NPC
      should be considered in patients with these various disorders. While some PNS
      will respond to direct treatment, most often the PNS subsides in parallel to
      response of the NPC, and thus may be useful for monitoring tumor response or
      recurrence.

PMID- 19111999
TI  - Facial paralysis after superselective intra-arterial chemotherapy via the middle
      meningeal artery in maxillary cancer.
AB  - Previous studies have suggested that the severity of facial paralysis after
      superselective intra-arterial chemotherapy (SSIAC) is usually mild. Here we
      present two cases of facial paralysis after SSIAC via the middle meningeal artery
      (MMA). In case 1, the patient completely recovered from his facial paralysis (to
      H-B grade I) in 6 months after the onset of paralysis. However, in case 2, his
      facial movement remained at House-Brackmann (H-B) grade IV with severe
      synkinesis. We must be careful that SSIAC via the MMA may potentially increase
      the risk of facial paralysis.

PMID- 19112000
TI  - WITHDRAWN: Methicillin-resistant Staphylococcus aureus among a network of French
      private-sector community-based-medical laboratories.
AB  - Cet article a du etre retire conformement a la ligne de conduite d'Elsevier
      concernant le retrait d'articles. Vous pouvez consulter le site
      (http://www.elsevier.com/locate/withdrawalpolicy) pour de plus amples
      renseignements. L'editeur vous prie d'accepter ses excuses pour ce desagrement.

PMID- 19112001
TI  - Differential expression of aquaporin-4 in human gastric normal and cancer
      tissues.
AB  - BACKGROUND AND OBJECTIVE: Aquaporin-4 (AQP4) is a member of the water channel
      protein family, which is thought to be associated with tumor development. A
      recent work suggests that AQP play key roles in tumor biology. METHODS: In this
      study, we measured the expression and localization of AQP4 in 60 gastric
      epithelial tumor cases and 10 normal tissue cases by immunohistochemistry,
      Western blotting and RT-PCR analysis. RESULTS: AQP4 protein and mRNA expression
      level in gastric cancer tissue were significantly lower than those in normal
      gastric tissue. No significant variations were found according to TNM stage,
      histological type, grade and distant metastasis. CONCLUSION: Our results suggest
      that the expression of AQP4 is a marker of normal proliferating gastric
      epithelial cells. More cases and further research may be necessary to elucidate
      their exact role in normal or pathologic proliferation and/or differentiation.

PMID- 19112002
TI  - Ex vivo MRI of axillary lymph nodes in breast cancer.
AB  - PURPOSE: To provide a strategy for precise co-localization of lymph nodes on
      axillary lymph-node dissection (ALND) specimens both on pathology and MR. To
      identify nodal features suggestive of metastatic involvement on a node-to-node
      basis. MATERIALS AND METHODS: National Institutional review-board approved this
      prospective study of 18 patients with breast cancer referred for ALND. Ex vivo T1
      and inversion recovery (IR) T2 WI of ALND specimens tightly positioned within
      scaled plastic cranes was performed immediately after surgery. The correspondence
      of MR-based or pathologically based nodes location was assessed. The MR size and
      morphological presentation of metastatic and normal nodes were compared
      (Student's t-test or Mann-Whitney test). Quantitative variables were compared
      using Pearson coefficient. RESULTS: 207 nodes were retrieved on pathology and 165
      on MR. MR-pathological correlation of nodes location was high regarding MR
      identified nodes (r=0.755). An MR short axis threshold of 4mm yielded the best
      predictive value for metastatic nodal involvement (Se=78.6%; Sp=62.3%). Irregular
      contours (Se=35.7%; Sp=96.7%), central nodal hyper-intensity on IR T2 WI
      (Se=57.1%; Sp=91.4%), and a cortical thickness above 3mm (Se=63.6%; Sp=83.2%)
      were significantly associated with metastatic involvement. CONCLUSION: Ex vivo MR
      allows node-to-node correlation with pathology. Morphological MR criteria can
      suggest metastatic involvement.

PMID- 19112003
TI  - Determination of hydrate transition temperature using transformation kinetics
      obtained by Raman spectroscopy.
AB  - The thermodynamic transition temperature is a key parameter to ascertain when
      assessing the properties of a crystalline hydrate. The transition temperature is
      sometimes difficult to determine experimentally due to rapid transformation
      between the two crystal forms in solution. In this study, a new approach for
      determining the transition temperature is presented, utilizing the temperature
      dependence of the transformation kinetics in aqueous slurries, as determined
      using in-line Raman spectroscopy. The transition temperatures of several hydrate
      forming compounds, namely theophylline, carbamazepine and caffeine, are
      presented. In general, good correlations with literature values were found. This
      method was found to be a simple, fast and reliable approach for the determination
      of crystal hydrate transition temperatures in aqueous environments.

PMID- 19112004
TI  - Live conjoined twins: a rare first trimester diagnosis during emergency
      department sonography.
AB  - BACKGROUND: The evaluation of vaginal bleeding and pelvic pain in the first
      trimester of pregnancy is an important component of emergency physician training.
      The increased use of bedside sonography by emergency physicians in the evaluation
      of these patients requires knowledge about the normal anatomy, variants, abnormal
      findings and their appearance on sonography. OBJECTIVES: To highlight the
      importance of a thorough pelvic and abdominal sonographic examination during a
      routine evaluation in the emergency department (ED). CASE REPORT: We present the
      case of a patient found to have conjoined twins diagnosed by ED sonography.
      CONCLUSION: A discussion of the diagnosis, the findings on bedside sonogram and
      management options are presented.

PMID- 19112005
TI  - Treatment and outcome of radiation-induced soft-tissue sarcomas at a specialist
      institution.
AB  - BACKGROUND: Radiation-induced sarcoma (RIS) is a rare late complication of
      therapeutic irradiation with a reputation for aggressive pathology and poor
      outcome. METHODS: We retrospectively reviewed histopathological features, surgery
      and outcome in 67 patients with RIS treated between 1990 and 2005 at a single
      tertiary referral center. RESULTS: Previous breast cancer was the most common
      indication for radiotherapy. The median interval from irradiation to development
      of RIS of was 11 years (3-36 years). Median tumour size was 7 cm with 56%
      classified as high grade, 31% intermediate grade and 13% low grade. The commonest
      histology was leiomyosarcoma. The only relationship for histology with site was
      for angiosarcoma (n=9), all of which developed on the chest wall/breast after
      irradiation for breast cancer. Of 67 patients, 34 underwent potentially curative
      surgery, and microscopically clear margins were achieved in 75% of cases.
      Pedicled or free tissue transfer was required in 12 patients and abdominal or
      chest wall mesh reconstructions were required in 8 patients. No patient received
      adjuvant radiotherapy but 7 received adjuvant/neoadjuvant chemotherapy. Median
      follow up is 53 months. Median sarcoma specific survival was 54 months (2- & 5
      year survival: 75% & 45%). The local relapse rate was 65%. Negative
      histopathological margins were a significant predictor of sarcoma specific
      survival (HR 3.0 95% CI 1.1-8.6 p=0.04). Grade and size of tumour approached, but
      did not attain significance. CONCLUSION: RIS is a biologically aggressive tumour
      with high rates of local relapse despite aggressive attempts at curative surgery.

PMID- 19112006
TI  - Does hyperbaric oxygen therapy improve quality of life?

PMID- 19112007
TI  - Comment on Letter to the Editor: Does hyperbaric oxygen therapy improve quality
      of life?

PMID- 19112008
TI  - Role of embCAB gene mutations in ethambutol resistance in Mycobacterium
      tuberculosis isolates from India.
AB  - In the present study, ethambutol (EMB) resistance-associated mutations were
      characterised in the embCAB genes of clinical isolates of Mycobacterium
      tuberculosis (MTB) collected in India. Thirty MTB isolates were tested for their
      susceptibility to first-line antitubercular drugs using the Lowenstein-Jensen
      proportion method, and EMB minimum inhibitory concentrations of MTB isolates were
      determined by the resazurin microtitre assay. Sequencing of various regions of
      the embCAB genes was performed to identify EMB resistance-associated mutations.
      Mutations of embB306 were detected in 15 of 23 EMB-resistant MTB isolates. Three
      EMB-resistant isolates had mutations at codon 270 of the embC gene, two of which
      also harboured embB306 mutations. No mutation was identified in the embA gene.
      All seven EMB-sensitive MTB isolates had the wild-type embCAB sequence. In
      summary, embB306 mutations were associated with EMB resistance, and mutation at
      codon 270 of the embC gene may contribute to high-level EMB resistance in some
      MTB isolates.

PMID- 19112009
TI  - A novel bactericidal fabric coating with potent in vitro activity against
      meticillin-resistant Staphylococcus aureus (MRSA).
AB  - We evaluated the antistaphylococcal activity of Cliniweave (CW), a commercially
      available textile treatment designed for use in healthcare environments. In tests
      on genetically diverse isolates of Staphylococcus aureus, including 49 meticillin
      resistant S. aureus (MRSA), the median minimum inhibitory concentration of the
      liquid compound was found to be 1 microg/L (range 0.5-2 microg/L). Comparison of
      the antimicrobial activity of CW-treated polyester with three other commercially
      available silver-based antimicrobial fabrics showed that after exposure of
      cultures of ca. 10(6) colony-forming units/mL of S. aureus, only CW-treated
      fabric showed any significant antibacterial activity, severely reducing bacterial
      numbers within 1h. Time-kill analysis of liquid CW in culture showed 2 log and 3
      log reductions of S. aureus numbers within 30 min and 240 min, respectively, and
      2 log reductions were observed within 60 min using treated fabric. CW-treated
      fabrics are strongly biocidal and may be useful in helping reduce the burden of
      nosocomial bacterial infection.

PMID- 19112010
TI  - [Febrile torticollis: an atypical presentation of Kawasaki disease].
AB  - Kawasaki disease is a form of idiopathic systemic vasculitis. Diagnosis is based
      upon specific clinical parameters. Cardiac manifestations explain the mortality
      rate. They can be reduced by early treatment using intravenous immunoglobulin.
      Atypical Kawasaki disease is difficult to diagnose and can delay diagnosis. We
      report a case of Kawasaki disease with arthritis in a 4-year-old girl whose
      initial presentation was a febrile torticollis. A literature review details the
      atypical early signs of Kawasaki disease revealed by torticollis.

PMID- 19112011
TI  - A hybrid hierarchical decision support system for cardiac surgical intensive care
      patients. Part II. Clinical implementation and evaluation.
AB  - OBJECTIVE: Patients emerging from cardiac surgery can display varying degrees of
      cardiovascular instability arising from potentially complex, multi-factorial and
      interlinked causes. Stabilization and control of the cardiovascular system are
      currently managed by healthcare experts using experiential knowledge, and, in
      some centers, manually inputted decision pathway algorithms. This paper describes
      a clinical trial undertaken to determine the basic functioning of a clinical
      decision support system (CDSS) designed and constructed by the authors to
      facilitate the control of the major cardiovascular components in the early post
      operative phase. Part II follows Part I's description of the software and
      simulation testing of the CDSS, and describes the hardware setup of a patient
      monitoring and CDSS. The system is evaluated on three post-cardiac surgery
      intensive care patients whom had all undergone cardio-pulmonary bypass. METHODS:
      The study was approved by the Sheffield Teaching Hospitals National Health
      Service (NHS) Foundation Trust Research Ethics Committee and conducted at the
      North Trent cardio-thoracic surgical unit and cardiac intensive care unit (CICU),
      Northern General Hospital, Sheffield (UK). Patients considered as 'very likely'
      to require active intervention to support the cardiovascular function following
      routine cardiac surgery were recruited during pre-operative surgical and
      anesthetic assessment, giving written informed consent when admitted for their
      operation. These patients underwent routine induction and maintenance of
      anesthesia by a non-study consultant anesthetist and the operation performed.
      There were no restrictions placed on the types of invasive monitoring used, on
      the use of trans-oesophageal echocardiography, drug selection, or the anesthetic
      agents selected by the clinicians performing the operations. All patients had
      full, routine invasive and non-invasive monitoring applied, including
      electrocardiography, central venous and peripheral arterial catheterisation,
      urine outputs and central temperature. After chest closure the patients were
      transferred to the CICU, sedated and ventilated, and the study commenced by the
      study anesthetist (1st author). The patients were in a clinically stable
      condition when admitted to the unit, and were attended by the treating clinicians
      until the handover to the study anesthetist occurred. The LiDCOplus (lithium
      dilution cardiac output) monitor (LiDCO Limited, Flowers Building, Granta Park,
      Cambridge CB1 6GU, United Kingdom) was calibrated after attachment to the
      patient's arterial line, and the patient's beat-to-beat hemodynamic data
      transferred to the host laptop computer. The CDSS graphical interface displays
      the patient's clinical details and specific cardiovascular data and prompts the
      anesthetist to input the target ranges for each parameter, and select a suitable
      advisor frequency. This is the frequency with which the therapeutic advice is
      displayed on screen with an audible prompt for a control inputs from the
      anesthetist. In each case this was selected to be 30s. When the study anesthetist
      agreed with the CDSS advice (administration of fluid, commencing a drug, altering
      the drug infusion rate) the syringe motif on the "Advisor Infusion Rates" panel
      of the graphical interface was 'clicked' on and the infusion rate immediately and
      manually inputted to Graseby 3400 pumps. If any disagreement between the
      anesthetist and the computer's advice arose, the syringe motif on the "Expert
      Infusion Rates" panel of the preferred drug was 'clicked' on and the expert's
      therapeutic decision (e.g. infusion rate) was entered in the corresponding data
      field and then applied to the pump. During all trials, data was stored for off
      line analysis. RESULTS: The CDSS successfully selected suitable drug therapies
      for each case and advised reasonable and appropriate infusion rates such that the
      study anesthetist did not have to override the suggested CDSS instructions and
      infusion rates. Under differing clinical conditions the system was able to
      maintain clinically appropriate and stable control of the cardiovascular system
      (CVS), with good profiles under noisy physiological measurements, and was readily
      able to regain control following transient deterioration of the patient
      hemodynamic parameters (coughing, or during blood sampling).

PMID- 19112012
TI  - A hybrid hierarchical decision support system for cardiac surgical intensive care
      patients. Part I: Physiological modelling and decision support system design.
AB  - OBJECTIVE: To develop a clinical decision support system (CDSS) that models the
      different levels of the clinician's decision-making strategies when controlling
      post cardiac surgery patients weaned from cardio pulmonary bypass. METHODS: A
      clinical trial was conducted to define and elucidate an expert anesthetists'
      decision pathway utilised in controlling this patient population. This data and
      derived knowledge were used to elicit a decision-making model. The structural
      framework of the decision-making model is hierarchical, clearly defined, and
      dynamic. The decision levels are linked to five important components of the
      cardiovascular physiology in turn, i.e. the systolic blood pressure (SBP),
      central venous pressure (CVP), systemic vascular resistance (SVR), cardiac output
      (CO), and heart rate (HR). Progress down the hierarchy is dependent upon the
      normalisation of each physiological parameter to a value pre-selected by the
      clinician via fluid, chronotropes or inotropes. Since interventions at each and
      every level cause changes and disturbances in the other components, the proposed
      decision support model continuously refers back decision outcomes back to the SBP
      which is considered to be the overriding supervisory safety component in this
      hierarchical decision structure. The decision model was then translated into a
      computerised decision support system prototype and comprehensively tested on a
      physiological model of the human cardiovascular system. This model was able to
      reproduce conditions experienced by post-operative cardiac surgery patients
      including hypertension, hypovolemia, vasodilation and the systemic inflammatory
      response syndrome (SIRS). RESULTS: In all the simulated patients scenarios
      considered the CDSS was able to initiate similar therapeutic interventions to
      that of the expert, and as a result, was also able to control the hemodynamic
      parameters to the prescribed target values.

PMID- 19112013
TI  - Nanoporous cerium oxide thin film for glucose biosensor.
AB  - Nanoporous cerium oxide (CeO(2)) thin film deposited onto platinum (Pt) coated
      glass plate using pulsed laser deposition (PLD) has been utilized for
      immobilization of glucose oxidase (GOx). Atomic force microscopy studies reveal
      the formation of nanoporous surface morphology of CeO(2) thin film. Response
      studies carried out using differential pulsed voltammetry (DPV) and optical
      measurements show that the GOx/CeO(2)/Pt bio-electrode shows linearity in the
      range of 25-300 mg/dl of glucose concentration. The low value of Michaelis-Menten
      constant (1.01 mM) indicates enhanced enzyme affinity of GOx to glucose. The
      observed results show promising application of the nanoporous CeO(2) thin film
      for glucose sensing application without any surface functionalization or
      mediator.

PMID- 19112014
TI  - Design and validation of a low cost surface plasmon resonance bioanalyzer using
      microprocessors and a touch-screen monitor.
AB  - An economical and high-performance bioanalyzer, with no use of laptop computer,
      based on the use of TSPR1k23 biosensors was systematically designed, and
      validated experimentally for its high performance. The analyzer is composed of a
      micro-flow cell, a thermoelectric cooler (TEC), a clamp, a touch-screen monitor,
      and an electronic control unit (ECU) incorporated with photoelectric conversion
      device. The micro-flow cell is made of stainless steel with high thermal
      conductivity, and the micro-flow system is based on PID temperature-controlled
      algorithm to keep the constant temperature (25 degrees C) of the liquid sample
      via thermal exchange with the clamp. With a peristaltic pump implemented by an
      injection loop flow system, the bioanalyzer allows the core sensor to be
      completely exposed to samples. The touch-screen monitor displays the normalized
      response signal values updated every 0.25s, with a typical noise level less than
      5RU (response unit) within 2h. The bioanalyzer was validated using hepatitis B
      surface antigen (HBsAg) as an example. Anti-HBsAg monoclonal antibody is adhered
      to the surface of the sensor chip by a bifunctional cross-linker with the
      technology of self-assembly. The duration of the HBsAg measurement only lasts
      5min with a dilution factor ranging from 200 to 1200, optimized with a R-squared
      value 0.998. The results suggested that the bioanalyzer has higher selectivity,
      lower cost, expanded detection limit, and shorter measuring time as compared with
      the HBsAg ELISA kit, especially for low concentrations of analyte.

PMID- 19112015
TI  - Endo180 expression with cofunctional partners MT1-MMP and uPAR-uPA is correlated
      with prostate cancer progression.
AB  - Endo180 (CD280; MRC2; uPARAP) regulates collagen remodelling and chemotactic cell
      migration through cooperation with membrane type-1 matrix metalloproteinase (MT1
      MMP), urokinase-type plasminogen activator receptor (uPAR) and urokinase-type
      plasminogen activator (uPA). One hundred and sixty nine prostate tissue sections
      clinically graded as benign prostatic hyperplasia (BPH) (n=29) or prostate cancer
      (PCA) with Gleason scores indicating low (< or =7(3+4); n=26), intermediate
      (7(4+3)-8; n=96) or high (9-10; n=19) clinical risk were immunofluorescently
      stained for Endo180, pan-cytokeratin (pCk), vimentin, MT1-MMP and uPAR-uPA.
      Quantification of % Endo180(+)/pCk(-) and Endo180(+)/pCk(+) cells in entire
      tissue cores revealed stromal (p=0.0001) and epithelial (p=0.0001) upregulation
      of Endo180 in PCA compared to BPH. Epithelial Endo180 expression was
      significantly different between the three clinical risk groups of PCA (p<0.05).
      Correlations with MT1-MMP and uPAR-uPA confirmed the functionality of Endo180
      during PCA progression. This molecular evaluation is the first step in the
      exploration of Endo180 in PCA diagnosis and therapy.

PMID- 19112016
TI  - Xanthine oxidoreductase - clinical significance in colorectal cancer and in vitro
      expression of the protein in human colon cancer cells.
AB  - Xanthine oxidoreductase (XOR) is a key enzyme in degradation of DNA and RNA, and
      has previously been shown to be decreased in aggressive breast and gastric
      cancer. In this study, XOR expression was assessed in tissue microarray specimens
      of 478 patients with colorectal cancer and related to clinical parameters. In
      addition, we performed in vitro studies of XOR activity, protein and mRNA in
      colon cancer cells (Caco-2). Results from the tissue expression analyses show
      that XOR was decreased in 62% and undetectable in 22% of the tumours as compared
      to normal tissue. Loss of XOR was associated with poor grade of differentiation
      (p=0.006) and advanced Dukes stage (p=0.03). In multivariate survival analysis,
      XOR was a prognostic factor (p=0.008), independent of Dukes stage, histological
      grade, age and tumour location. The in vitro analyses show that XOR is not
      measurable in undifferentiated Caco-2 cells, but appears and increases with
      differentiation. We conclude that XOR expression is associated with histological
      grade of differentiation and extent of disease in colorectal cancer, and it
      provides significant prognostic information independently of established factors.

PMID- 19112017
TI  - Selection and characterization of a human monoclonal neutralizing antibody for
      Clostridium Botulinum neurotoxin serotype B.
AB  - Botulinum neurotoxins (BoNTs) are causative agents for botulism and are
      identified as a category A bioterror agents by the Centers for Disease Control
      and Prevention (CDC). Current antitoxins against BoNTs intoxication have some
      limitations including side effects or limited supply. As an alternative,
      neutralizing monoclonal antibodies will play an increasing role as BoNTs
      therapeutics. To date, no human anti-BoNT/B neutralizing monoclonal antibodies
      have yet to be reported. Herein, we describe an improved selection approach and
      characterization of a human monoclonal antibody, F2, which is capable of binding
      BoNT/B with high specificity and displays neutralizing activity in an in vitro
      cell-based assay. Through surface plasmon resonance studies, we have determined
      its association and dissociation rate constants. In sum, our data demonstrate
      that monoclonal antibody F2 is a promising BoNT/B therapeutic lead for further
      development.

PMID- 19112018
TI  - Identification of 3-amido-4-anilinoquinolines as potent and selective inhibitors
      of CSF-1R kinase.
AB  - 3-amido-4-anilinoquinolines are potent and highly selective inhibitors of CSF-1R.
      Their synthesis and SAR is reported, along with initial efforts to optimize the
      physical properties and PK through modifications at the quinoline 6- and 7
      positions.

PMID- 19112019
TI  - Curcumin is a potent DNA hypomethylation agent.
AB  - Molecular docking of the interaction of curcumin and DNMT1 suggested that
      curcumin covalently blocks the catalytic thiolate of C1226 of DNMT1 to exert its
      inhibitory effect. This was validated by showing that curcumin inhibits the
      activity of M. SssI with an IC(50) of 30 nM, but no inhibitory activity of
      hexahydrocurcumin up to 100 microM. In addition, curcumin can induce global DNA
      hypomethylation in a leukemia cell line.

PMID- 19112020
TI  - New potential inhibitors of DNA topoisomerase. Part II: Design and synthesis of
      alpha-lapachone derivatives under microwave irradiation.
AB  - A new series of potential inhibitors of DNA topoisomerase II were synthesized
      from facile materials (aromatic aldehydes, Meldrum's acid and 2
      hydroxynaphthalene-1,4-dione) under microwave irradiation. The method provides a
      valuable tool in designing new and more potent cytotoxic analogues. This
      procedure is advantageous both economically and environmentally.

PMID- 19112022
TI  - Close relatives' experiences of caring and of the physical environment when a
      loved one dies in an ICU.
AB  - AIM: The aim of this study was to explore close relatives' experiences of caring
      and the physical environment when a loved one dies in an intensive care unit
      (ICU). METHOD: Interviews were conducted with 17 close relatives of 15 patients
      who had died in three adult ICUs. The interviews were analysed using a
      phenomenological-hermeneutic method. FINDINGS: The analysis resulted in seven
      themes; Being confronted with the threat of loss, Maintaining a vigil, Trusting
      the care, Adapting and trying to understand, Facing death, The need for privacy
      and togetherness and Experiencing reconciliation. The experience of a caring
      relationship was central, which meant that the carers piloted the close relatives
      past the hidden reefs and through the dark waters of the strange environment,
      unfamiliar technology, distressing information and waiting characterised by
      uncertainty. Not being piloted meant not being invited to enter into a caring
      relationship, not being allowed access to the dying loved one and not being
      assisted in interpreting information. CONCLUSION: The participants showed
      forbearance with the ICU-environment. Their dying loved one's serious condition
      and his or her dependence on the medical-technical equipment were experienced as
      more frightening than the equipment as such. Returning for a follow-up-visit
      provided an opportunity for reconciliation and relief from guilt.

PMID- 19112021
TI  - Integrating the stress response: lessons for neurodegenerative diseases from C.
      elegans.
AB  - All cells possess surveillance and homeostatic mechanisms to adjust protein
      biogenesis to the demands of growth, differentiation, ageing and environmental
      stress. However, under certain circumstances, these mechanisms fail to adequately
      respond to proteotoxic imbalances and result in the accumulation of misfolded
      proteins. In humans, this can lead to neurodegeneration and other protein
      conformational diseases. To protect itself, the cell employs highly conserved
      stress responses and chaperone networks to maintain protein-folding homeostasis
      (proteostasis). Although the regulation of stress responses, such as the heat
      shock response, and of proteostasis have been widely considered to be cell
      autonomous, recent studies using Caenorhabditis elegans have shown that these
      processes are regulated by neuronal signaling and endocrine pathways and
      integrated into other functions of the organism. The hierarchical control of the
      cellular proteostasis machinery affords insight into the organization of stress
      regulatory networks in multicellular organisms and offers novel targets for the
      treatment of human protein conformational diseases.

PMID- 19112023
TI  - Nonlinear spatial warping for between-subjects pedobarographic image
      registration.
AB  - Foot size and shape vary between individuals and the foot adopts arbitrary stance
      phase postures, so traditional pedobarographic analyses regionalize foot pressure
      images to afford homologous data comparison. An alternative approach that does
      not require explicit anatomical labelling and that is used widely in other
      functional imaging domains is to register images such that homologous structures
      optimally overlap and then to compare images directly at the pixel level. Image
      registration represents the preprocessing cornerstone of such pixel-level
      techniques, so its performance warrants independent attention. The purpose of
      this study was to evaluate the performance of four between-subjects warping
      registration algorithms including: Principal Axes (PA), four-parameter Optimal
      Scaling (OS4), eight-parameter Optimal Projective (OP8), and locally affine
      Nonlinear (NL). Fifteen subjects performed 10 trials of self-paced walking, and
      their peak pressure images were registered within-subjects using an optimal rigid
      body transformation. The resulting mean images were then registered between
      subjects using all four methods in all 210 (15x14) subject combinations. All
      registration methods improved alignment, and each method performed qualitatively
      well for certain image pairs. However, only the NL consistently performed
      satisfactorily because of disproportionate anatomical variation in toe lengths
      and rearfoot/forefoot width, for example. Using three independent image
      (dis)similarity metrics, MANOVA confirmed that the NL method yielded superior
      registration performance (p<0.001). These data demonstrate that nonlinear spatial
      warping is necessary for robust between-subject pedobarographic image
      registration and, by extension, robust homologous data comparison at the pixel
      level.

PMID- 19112024
TI  - Unified QSAR approach to antimicrobials. 4. Multi-target QSAR modeling and
      comparative multi-distance study of the giant components of antiviral drug-drug
      complex networks.
AB  - One limitation of almost all antiviral Quantitative Structure-Activity
      Relationships (QSAR) models is that they predict the biological activity of drugs
      against only one species of virus. Consequently, the development of multi-tasking
      QSAR models (mt-QSAR) to predict drugs activity against different species of
      virus is of the major vitally important. These mt-QSARs offer also a good
      opportunity to construct drug-drug Complex Networks (CNs) that can be used to
      explore large and complex drug-viral species databases. It is known that in very
      large CNs we can use the Giant Component (GC) as a representative sub-set of
      nodes (drugs) and but the drug-drug similarity function selected may strongly
      determines the final network obtained. In the three previous works of the present
      series we reported mt-QSAR models to predict the antimicrobial activity against
      different fungi [Gonzalez-Diaz, H.; Prado-Prado, F. J.; Santana, L.; Uriarte, E.
      Bioorg.Med.Chem.2006, 14, 5973], bacteria [Prado-Prado, F. J.; Gonzalez-Diaz, H.;
      Santana, L.; Uriarte E. Bioorg.Med.Chem.2007, 15, 897] or parasite species [Prado
      Prado, F.J.; Gonzalez-Diaz, H.; Martinez de la Vega, O.; Ubeira, F.M.; Chou K.C.
      Bioorg.Med.Chem.2008, 16, 5871]. However, including these works, we do not found
      any report of mt-QSAR models for antivirals drug, or a comparative study of the
      different GC extracted from drug-drug CNs based on different similarity
      functions. In this work, we used Linear Discriminant Analysis (LDA) to fit a mt
      QSAR model that classify 600 drugs as active or non-active against the 41
      different tested species of virus. The model correctly classifies 143 of 169
      active compounds (specificity=84.62%) and 119 of 139 non-active compounds
      (sensitivity=85.61%) and presents overall training accuracy of 85.1% (262 of 308
      cases). Validation of the model was carried out by means of external predicting
      series, classifying the model 466 of 514, 90.7% of compounds. In order to
      illustrate the performance of the model in practice, we develop a virtual
      screening recognizing the model as active 92.7%, 102 of 110 antivirus compounds.
      These compounds were never use in training or predicting series. Next, we
      obtained and compared the topology of the CNs and their respective GCs based on
      Euclidean, Manhattan, Chebychey, Pearson and other similarity measures. The GC of
      the Manhattan network showed the more interesting features for drug-drug
      similarity search. We also give the procedure for the construction of Back
      Projection Maps for the contribution of each drug sub-structure to the antiviral
      activity against different species.

PMID- 19112025
TI  - Isolation, structure and biological activity of phomafungin, a cyclic
      lipodepsipeptide from a widespread tropical Phoma sp.
AB  - We isolated a cyclic lipodepsipeptide, phomafungin, from a Phoma sp. The distinct
      antifungal activity of phomafungin in the crude extract was initially discovered
      by mechanistic profiling in the Candida albicans fitness test. The purified
      compound contains a 28 member ring consisting of eight amino acids and a beta
      hydroxy-gamma-methyl-hexadecanoic acid, and displays a broad spectrum of
      antifungal activity against Candida spp., Aspergillus fumigatus and Trichophyton
      mentagrophytes with MIC of 2-8 microg/ml, and toxicity to mice at 25 mg/kg. The
      linear peptide derived from opening of the lactone ring was devoid of antifungal
      activity as well as toxicity. Phomafungin has been identified in a number of
      Phoma spp. collected from Africa and the Indian and Pacific Ocean islands.

PMID- 19112026
TI  - Azadirachtin, a scientific gold mine.
AB  - Azadirachtin is a highly interesting compound both for its chemical structure,
      which required 18 years to solve, and its synthesis, which required another 22
      years, and for its biological properties as a feeding deterrent for many insects
      and a growth disruptant for most insects and many other arthropods. Its mode of
      action, structure-activity relationships, and its biosynthesis still require much
      research. A valuable natural pesticide, it has very low toxicity for vertebrates,
      and yet it has still not achieved a prominent place among pesticides and in many
      countries it is not yet licensed for use. An attempt is made to understand its
      failure to capture a larger market, 40 years after its discovery.

PMID- 19112027
TI  - The influence of material and mesh characteristics on transmission mode
      desorption electrospray ionization.
AB  - Adaptation of desorption electrospray ionization to a transmission mode (TM-DESI)
      entails passing an electrospray plume through a sample that has been deposited
      onto a mesh substrate. A combination of mass spectrometry and fluorescence
      microscopy studies is used to illustrate the critical role material composition,
      mesh open space, and mesh fiber diameter play on the transmission, desorption,
      and ionization process. Substrates with open spaces less than 150 microm and
      accompanying minimal strand diameters produce less scattering of the plume and
      therefore favor transmission. Larger strand diameters typically encompass larger
      open spaces, but the increase in the surface area of the strand increases plume
      scattering as well as solvent and analyte spreading on the mesh. Polypropylene
      (PP), ethylene tetrafluoroethylene (ETFE), and polyetheretherketone (PEEK)
      materials afford much better desorption than similarly sized polyethylene
      terephthalate (PETE) or nylon-6,6 (PA66) substrates. Ultimately, the manner in
      which the electrospray plume interacts with the mesh as it is transmitted through
      the substrate is shown to be critical to performing and optimizing TM-DESI
      analyses. In addition, evidence is presented for analyte dependent variations in
      the desorption mechanisms of dry and solvated samples.

PMID- 19112028
TI  - Electron capture and transfer dissociation: Peptide structure analysis at
      different ion internal energy levels.
AB  - We decoupled electron-transfer dissociation (ETD) and collision-induced
      dissociation of charge-reduced species (CRCID) events to probe the lifetimes of
      intermediate radical species in ETD-based ion trap tandem mass spectrometry of
      peptides. Short-lived intermediates formed upon electron transfer require less
      energy for product ion formation and appear in regular ETD mass spectra, whereas
      long-lived intermediates require additional vibrational energy and yield product
      ions as a function of CRCID amplitude. The observed dependencies complement the
      results obtained by double-resonance electron-capture dissociation (ECD) Fourier
      transform ion cyclotron resonance mass spectrometry (FT-ICR MS) and ECD in a
      cryogenic ICR trap. Compared with ECD FT-ICR MS, ion trap MS offers lower
      precursor ion internal energy conditions, leading to more abundant charge-reduced
      radical intermediates and larger variation of product ion abundance as a function
      of vibrational post-activation amplitude. In many cases decoupled CRCID after ETD
      exhibits abundant radical c-type and even-electron z-type ions, in striking
      contrast to predominantly even-electron c-type and radical z-type ions in ECD FT
      ICR MS and especially activated ion-ECD, thus providing a new insight into the
      fundamentals of ECD/ETD.

PMID- 19112029
TI  - Generation of multiply charged peptides and proteins by radio frequency acoustic
      desorption and ionization for mass spectrometric detection.
AB  - The design and implementation of a radio frequency acoustic desorption ionization
      (RADIO) source has been demonstrated for the analysis of multiply charged
      peptides and proteins. One muL aliquots of melittin, BNP-32, and ubiquitin (
      approximately 1 mug of analyte) were deposited onto a quartz crystal microbalance
      (QCM) electrode before radio frequency actuation for desorption. Continuous
      electrospray parallel to/above the sampling surface enabled the ionization of
      desorbed species. Detection by a hybrid linear ion trap Fourier transform ion
      cyclotron resonance mass spectrometer confirmed the intact and dissociated
      species observed during MS and MS/MS experiments, respectively.

PMID- 19112030
TI  - Radiology afloat: The impact of diagnostic and interventional radiology during
      the 2005 tsunami relief effort aboard the USNS Mercy.

PMID- 19112031
TI  - Treatment of metastatic carcinoma to the hip with CT-guided percutaneous
      acetabuloplasty: report of four cases.
AB  - Percutaneous acetabuloplasty (PA) is a promising treatment for painful metastatic
      lesions of the acetabulum. Four patients were treated with injection of the bone
      cement polymethylmethacrylate directly into the lesion. After the procedure, all
      four patients had improvement or relief of their pain and were able to resume
      weight-bearing activities. The procedure was well tolerated by each patient
      without morbidity. PA appears to be a reasonable palliative procedure for painful
      and fragile hips associated with metastatic bone disease.

PMID- 19112032
TI  - The effects of cilostazol on exercise-induced ischaemia-reperfusion injury in
      patients with peripheral arterial disease.
AB  - OBJECTIVES: Cilostazol improves walking distance in peripheral arterial disease
      (PAD) patients. The study objectives were to assess the effects of cilostazol on
      walking distance, followed by the additional assessment of cilostazol on exercise
      induced ischaemia-reperfusion injury in such patients. METHODS: PAD patients were
      prospectively recruited to a double-blinded, placebo-controlled trial. Patients
      were randomised to receive either cilostazol 100mg or placebo twice a day. The
      primary end-point was an improvement in walking distance. Secondary end-points
      included the assessment of oxygen-derived free-radical generation, antioxidant
      consumption and other markers of the inflammatory cascade. Initial and absolute
      claudication distances (ICDs and ACDs, respectively) were measured on a
      treadmill. Inflammatory response was assessed before and 30 min post-exercise by
      measuring lipid hydroperoxide, ascorbate, alpha-tocopherol, beta-carotene, P
      selectin, intracellular and vascular cell-adhesion molecules (I-CAM and V-CAM),
      thromboxane B(2) (TXB(2)), interleukin-6, interleukin-10, high-sensitive C
      reactive protein (hsCRP), albumin-creatinine ratio (ACR) and urinary levels of
      p75TNF receptor. All tests were performed at baseline and 6 and 24 weeks.
      RESULTS: One hundred and six PAD patients (of whom 73 were males) were recruited
      and successfully randomised from December 2004 to January 2006. Patients who
      received cilostazol demonstrated a more significant improvement in the mean
      percentage change from baseline in ACD (77.2% vs. 26.6% at 6 weeks, p=0.026 and
      161.7% vs. 79.0% at 24 weeks, p=0.048) as compared to the placebo. Cilostazol
      reduced lipid hydroperoxide levels compared to a placebo-related increase before
      and after exercise (6 weeks: pre-exercise: -11.8% vs. +5.8%, p=0.003 and post
      exercise: -12.3% vs. +13.9%, p=0.007 and 24 weeks: pre-exercise -15.5% vs.
      +12.0%, p=0.025 and post-exercise: -9.2% vs. +1.9%, p=0.028). beta-Carotene
      levels were significantly increased in the cilostazol group, compared to placebo,
      before exercise at 6 and 24 weeks (6 weeks: 34.5% vs. -7.4%, p=0.028; 24 weeks:
      34.3% vs. 17.7%, p=0.048). Cilostazol also significantly reduced P-selectin, I
      CAM and V-CAM levels at 24 weeks as compared to baseline (p<0.05). There was no
      difference between treatment groups for ascorbate, alpha-tocopherol, interleukin
      6 and -10, hsCRP and p75TNF receptor levels. CONCLUSIONS: Cilostazol
      significantly improves ACD, in addition to attenuating exercise-induced ischaemia
      reperfusion injury, in PAD patients.

PMID- 19112033
TI  - Long-term outcomes after angioplasty of isolated, below-the-knee arteries in
      diabetic patients with critical limb ischaemia.
AB  - BACKGROUND: It has been shown that concomitant percutaneous transluminal
      angioplasty (PTA) of above-the-knee (ATK) and below-the-knee (BTK) arteries is
      highly beneficial for limb salvage in patients with critical limb ischaemia
      (CLI), but few published studies have specifically investigated outcomes in
      diabetic patients with CLI associated with isolated small BTK-vessel disease.
      This study aimed to evaluate the long-term results of successful PTA for limb
      salvage in such patients. MATERIALS AND METHODS: From among the 634 patients with
      CLI in our database, we retrospectively selected a consecutive series of 101
      diabetics (16%) with 107 critically ischaemic limbs (33 Rutherford 5 and 74
      Rutherford 6) and no critical ATK lesion, who underwent PTA on isolated BTK
      lesions. RESULTS: The limb salvage rate was 93% after a mean follow-up of 1048+/
      525 days (2.9+/-1.4 years). Transcutaneous oxygen tension significantly increased
      after 1 month (18.1+/-11.2 vs. 39.6+/-15.1; p<0.05). After 1 year, target-vessel
      re-stenosis had occurred in 42% of the non-amputated limbs, nine patients (9%)
      had died because of medical conditions unrelated to PTA and three patients had
      undergone repeat PTA for recurrent CLI. CONCLUSIONS: In our selected patient
      population with ischaemic diabetic foot and isolated BTK lesions, a successful
      endovascular procedure led to a high percentage of limb salvage at long-term
      follow-up.

PMID- 19112034
TI  - Molecular pathology in vulnerable carotid plaques: correlation with [18]
      fluorodeoxyglucose positron emission tomography (FDG-PET).
AB  - OBJECTIVES: Atherosclerosis is recognised as an inflammatory disease, and new
      diagnostic tools are warranted to evaluate plaque inflammatory activity and risk
      of cardiovascular events. We investigated [18]-fluorodeoxyglucose (FDG) uptake in
      vulnerable carotid plaques visualised by positron emission tomography (PET).
      Uptake was correlated to quantitative gene expression of known markers of
      inflammation and plaque vulnerability. METHODS: Ten patients with recent
      transient ischaemic attack and carotid artery stenosis (>50%) underwent combined
      FDG-PET and computed tomography angiography (CTA) the day before carotid
      endarterectomy. Plaque mRNA expression of the inflammatory cytokine interleukin
      18 (IL-18), the macrophage-specific marker CD68 and the two proteinases,
      Cathepsin K and matrix metalloproteinase 9 (MMP-9), were quantified using real
      time quantitative polymerase chain reaction. RESULTS: Consistent up-regulation of
      CD68 (3.8-fold+/-0.9; mean+/-standard error), Cathepsin K (2.1-fold+/-0.5), MMP-9
      (122-fold+/-65) and IL-18 (3.4-fold+/-0.7) were found in the plaques, compared to
      reference-artery specimens. The FDG uptake by plaques was strongly correlated
      with CD68 gene expression (r=0.71, P=0.02). Any correlations with Cathepsin K,
      MMP-9 or IL-18 gene expression were weaker. CONCLUSIONS: FDG-PET uptake in
      carotid plaques is correlated to gene expression of CD68 and other molecular
      markers of inflammation and vulnerability.

PMID- 19112035
TI  - In vivo hyperpolarized 13C MR spectroscopic imaging with 1H decoupling.
AB  - Application of (13)C MRS in vivo on whole body MR system has been limited due to
      the low static field (and consequent low signal to noise ratio-SNR) of these
      scanners; thus there have been few reports of (1)H decoupled (13)C MRS in vivo
      using a clinical MR platform. The recent development of techniques to retain
      highly polarized spins in solution following DNP in a solid matrix has provided a
      mechanism to use endogenous pre-polarized (13)C labeled substrates to study real
      time cellular metabolism in vivo with high SNR. In a recent in vivo
      hyperpolarized metabolic imaging study using (13)C pyruvate, it has been
      demonstrated that the line shape (signal decay) of the resonances observed are
      greatly affected by J(CH) coupling in addition to inhomogeneous broadening. This
      study demonstrates the feasibility of improving hyperpolarized (13)C metabolic
      imaging in vivo by incorporating (1)H decoupling on a clinical whole body 3T MR
      scanner. No reduction of T1 of a pre-polarized (13)C substrate ([1-(13)C]
      lactate) in solution was observed when (1)H decoupling was applied with WALTZ16
      sequence. Narrower linewidth for the [1-(13)C] lactate resonance was observed in
      hyperpolarized (13)C MRSI data in vivo with (1)H decoupling.

PMID- 19112036
TI  - Analysis of lymphocyte subgroups in Crimean-Congo hemorrhagic fever.
AB  - OBJECTIVES: This study examined the association between lymphocyte subgroups and
      mortality in patients with Crimean-Congo hemorrhagic fever (CCHF) in Turkey.
      METHODS: During the spring and summer of 2007, peripheral blood was collected
      from hospitalized patients with suspected CCHF. Lymphocyte subgroups were
      characterized by fluorescence-activated cell sorting. CCHF cases were confirmed
      by detecting viral RNA by PCR and/or IgM antibodies by ELISA. Lymphocyte
      subgroups were compared between fatal and non-fatal cases. The correlation
      between lymphocyte subgroups and viral loads was also investigated. RESULTS:
      Seventy-seven confirmed cases of CCHF were included in this study (five cases
      were fatal (6.5 %)). No differences in lymphocyte subgroups were found between
      fatal and non-fatal cases, except for significantly higher CD3+CD8+ T cells in
      the fatal cases (p=0.017). A positive correlation between viral load and CD3+CD8+
      T cells was also detected (p=0.044). There was no correlation between other
      lymphocyte subgroups and viral load. CONCLUSIONS: Higher levels of CD3+CD8+ T
      lymphocytes were detected in fatal compared to non-fatal CCHF cases. Despite this
      cytotoxic immune activation, a fatal outcome could not be prevented. We
      hypothesize that high viral load and other factors may influence this outcome,
      although more studies are required to explain the pathogenesis of CCHF.

PMID- 19112037
TI  - Studies with arylhydrazonopyridinones: Synthesis of new arylhydrazono thieno[3,4
      c]pyridinones as novel D2T2 dye class; classical verse green methodologies.
AB  - A variety of arylhydrazonopyridinones were prepared via heating cyanoacetamides
      with ethyl acetoacetate in absence of solvent under reflux conventionally or
      ultrasound irradiation or in a microwave oven. The formed products 5 and 6 could
      be readily converted to thienopyridones. Attempted addition of the latter to
      electron poor olefins afforded only arylhydrazonopyridinones.

PMID- 19112038
TI  - One-pot synthesis of benzylacetamide from oxime under ultrasound irradiation.
AB  - One-pot synthesis of benzylacetamide from oxime can be carried out in 80-95%
      yield at 35-40 degrees C under ultrasound irradiation. This method provided
      several advantages such as simple work-up procedure, shorter reaction time and
      higher yield.

PMID- 19112039
TI  - Effect of dissolved gas on efficacy of sonochemical reactors for microbial cell
      disruption: Experimental and numerical analysis.
AB  - In the present work the effect of dissolved gases on the extent of ultrasonically
      induced microbial cell disruption has been explored using a mathematical model
      and it has been validated by experimental data from literature. Degassing
      experiments are carried out and a degassing kinetics model for horn type
      ultrasonic device is presented. An overall model combining hydrodynamic and
      kinetics of cell disruption for horn type reactor is then proposed. The model
      includes several important operational parameters such as stress generated by the
      cavity, cell wall strength, dissolved gas concentration, degassing due to
      sonication, acoustic streaming generated due to sonication and attenuation of
      ultrasound in water. Model basically realizes in categorizing the volume of
      sonochemical reactor as active cavitation zone (ACZ) and inactive cavitation zone
      (ICZ). All the transformations are seen to occur only in ACZ. The two regions,
      i.e. ACZ and ICZ are assumed to behave as two mixed flow reactor arranged in
      closed loop. Suggestions have been also made for efficient design and scale up of
      ultrasonic devices for microbial cell disruption. The same model can be extended
      for other applications like particle size reduction, nano particle synthesis,
      leaching, emulsification with the knowledge of critical rate controlling
      parameter.

PMID- 19112040
TI  - Sonochemical synthesis of monodispersed magnetite nanoparticles by using an
      ethanol-water mixed solvent.
AB  - The magnetite nanoparticles were synthesized in an ethanol-water solution under
      ultrasonic irradiation from a Fe(OH)(2) precipitate. XRD, TEM, TG, IR, VSM and
      UV/vis absorption spectrum were used to characterize the magnetite nanoparticles.
      It was found that the formation of magnetite was accelerated in ethanol-water
      solution in the presence of ultrasonic irradiation, whereas, it was limited in
      ethanol-water solution under mechanical stirring. The monodispersibility of
      magnetite particles was improved significantly through the sonochemical synthesis
      in ethanol-water solution. The magnetic properties were improved for the samples
      synthesized under ultrasonic irradiation. This would be attributed to high Fe(2+)
      concentration in the magnetite cubic structure.

PMID- 19112041
TI  - Successful use of botulinum toxin for post-irradiation unilateral jaw
      neuromyotonia.

PMID- 19112042
TI  - Body building on land: morphological evolution of land plants.
AB  - Land plants are derived from green algal ancestors and made their first
      appearance on land 460 million years ago. The life cycle of the land plant body
      comprises two multicellular stages -- one haploid (gametophyte) and the other
      diploid (sporophyte). Recent discoveries suggest that the genes controlling
      diploid development in ancestral green algal zygotes diversified in the land
      plant lineage where they control the development of the diploid body plan. There
      are also numerous examples of the independent recruitment of sets of genes to
      control the development of structures that are morphologically and functionally
      similar. These discoveries are giving insights into the mechanism by which land
      plant morphologies changed over the past 460 million years.

PMID- 19112043
TI  - Growth and development: a broad view of fine detail.

PMID- 19112044
TI  - Synthesis, spectroscopic characterization, electrochemical behaviour and
      antibacterial activity of Ru(III) complexes of 2-[(4-N,N'
      dimethylaminophenylimino)-methyl]-4-halophenol.
AB  - The reaction of the chelating Schiff base ligands 2-[(4-N,N'
      dimethylaminophenylimino)-methyl]-4-X-phenol with [Ru(Cl)(3)(EPh(3))(3)]; (E=P or
      As); (X=Cl, Br or I) in the benzene afforded new stable ruthenium complexes of
      the general formula [Ru(Cl)(2)(EPh(3))(2)(L)] (L=anion of bidentate Schiff
      bases). The newly synthesized complexes were characterized using molar
      conductivity, spectral (UV-vis, FT-IR and EPR) and electrochemical studies. The
      molar conductance measurements proved that all these complexes are non
      electrolytes. All complexes show strong d-d transition in the visible region. The
      coordination of imine nitrogen and phenolic oxygen of ligands to ruthenium metal
      was confirmed with the change in the IR stretching frequency values. The EPR
      spectral data showed that the complexes are paramagnetic with one unpaired
      electrons. The redox behaviour of the complexes have been investigated by the
      cyclic voltammetric technique. All the complexes display an irreversible
      reduction (Ru(III)/Ru(II)) in the range of -0.826 to -0.971V. In view of the
      biological activity, the ligands and the complexes were observed that all the
      complexes showed moderate activity. Also the antibacterial activity of the ligand
      increased on chelation with metal ion.

PMID- 19112045
TI  - Vibrational spectroscopic investigations, ab initio and DFT studies on 7-bromo-5
      chloro-8-hydroxyquinoline.
AB  - The Fourier transform infrared (FTIR) and FT-Raman spectra of 7-bromo-5-chloro-8
      hydroxyquinoline (BCHQ) have been measured in the range 4000-400 and 4000-100cm(
      1), respectively. Complete vibrational assignment and analysis of the fundamental
      modes of the compound were carried out using the observed FTIR and FT-Raman data.
      The geometry was optimised without any symmetry constrains using the DFT/B3LYP
      and HF methods with 6-31G** basis set. The vibrational frequencies which were
      determined experimentally are compared with those obtained theoretically from ab
      initio HF and density functional theory (DFT) gradient calculations employing the
      HF/6-31G** and B3LYP/6-31G** methods for the optimised geometry of the compound.
      The structural parameters and normal modes of vibration obtained from HF and DFT
      methods are in good agreement with the experimental data. Normal coordinate
      analysis was also carried out with ab initio force fields utilising Wilson's FG
      matrix method.

PMID- 19112046
TI  - Influence of hydroxylation and glycosylation in ring A of soybean isoflavones on
      interaction with BSA.
AB  - In this paper, the influence of hydroxylation and glycosylation of soybean
      isoflavones in ring A on the interaction with BSA was investigated. Two soybean
      isoflavone aglycones (daidzein and genistein) and their glycosides (daidzin and
      genistin) were used to study their ability to bind BSA by quenching the BSA
      intrinsic fluorescence in solution. The hydroxylation and glycosylation of
      soybean isoflavones in ring A significantly affected the binding/quenching
      process; in general, the hydroxylation increases the binding affinity and the
      glycosylation decreased the binding affinity. For daidzein and daidzin, the
      binding constants for BSA were 5.2 x 10(4) and 5.58 x 10(3) L mol(-1),
      respectively. For genistein and genistin, the binding constants were 8.40 x 10(5)
      and 1.44 x 10(5) L mol(-1), respectively.

PMID- 19112047
TI  - Intensity changes in a continuous tone: auditory cortical potentials comparison
      with frequency changes.
AB  - OBJECTIVES: To examine auditory cortical potentials in normal-hearing subjects to
      intensity increments in a continuous pure tone at low, mid, and high frequency.
      METHODS: Electrical scalp potentials were recorded in response to randomly
      occurring 100 ms intensity increments of continuous 250, 1000, and 4000 Hz tones
      every 1.4 s. The magnitude of intensity change varied between 0, 2, 4, 6, and 8
      dB above the 80 dB SPL continuous tone. RESULTS: Potentials included N100, P200,
      and a slow negative (SN) wave. N100 latencies were delayed whereas amplitudes
      were not affected for 250 Hz compared to 1000 and 4000 Hz. Functions relating the
      magnitude of the intensity change and N100 latency/amplitude did not differ in
      their slope among the three frequencies. No consistent relationship between
      intensity increment and SN was observed. Cortical dipole sources for N100 did not
      differ in location or orientation between the three frequencies. CONCLUSIONS: The
      relationship between intensity increments and N100 latency/amplitude did not
      differ between tonal frequencies. A cortical tonotopic arrangement was not
      observed for intensity increments. Our results are in contrast to prior studies
      of brain activities to brief frequency changes showing cortical tonotopic
      organization. SIGNIFICANCE: These results suggest that intensity and frequency
      discrimination employ distinct central processes.

PMID- 19112048
TI  - Is the mode of occurrence of vesicoureteral reflux correlated to bladder function
      and spontaneous resolution?
AB  - PURPOSE: To investigate whether mode of occurrence of vesicoureteral reflux
      (VUR), during micturition (M), during filling without increase in pressure
      (passive, P) or in response to an overactive contraction (OA), can be explained
      by differences in bladder function. Also, to study if the mode of occurrence of
      VUR can predict spontaneous resolution. MATERIALS AND METHODS: There were 93
      infants (68 boys and 25 girls) with VUR (grade III-V) included. Videocystometry
      was performed at median ages 5, 22 and 32 months registering grade and mode of
      reflux and bladder function characteristics. RESULTS: Mode of occurrence of
      reflux changed with age. During infancy P, OA and M reflux comprised almost equal
      parts. At follow up, P reflux had increased and both OA and M reflux had
      decreased. This was partly due to a significantly higher probability of
      spontaneous resolution for M than P reflux, at 40 months (42 vs 18%). P and M
      reflux were significantly correlated to bladder function characteristics. P
      reflux was seen in children with high bladder capacity and occurred early in
      filling. Other predictors were higher age within the respective group and female
      sex. M reflux was correlated to lack of residual urine, low bladder capacity and
      absence of overactivity. Other indicators were male sex and low-grade reflux.
      CONCLUSIONS: P and M reflux correlate to different bladder patterns: P with high
      bladder capacity and M with low bladder capacity and without signs of bladder
      dysfunction. M seems to be benign with a higher resolution rate.

PMID- 19112049
TI  - Daptomycin for methicillin-resistant Staphylococcus aureus infections of the
      spine.
AB  - BACKGROUND: Methicillin-resistant Staphylococcus aureus (MRSA) infection is
      increasingly common. Treatment with vancomycin-based therapy is often
      unsuccessful. Daptomycin is a relatively new lipopeptide antibiotic with potent
      activity against MRSA. PURPOSE: To describe the successful management of MRSA
      infection involving the spine. STUDY DESIGN: Two case reports of MRSA infection,
      one involving epidural and lumbar subdural abscesses, the other with
      osteomyelitis and discitis. METHODS: Two cases are described, one with lumbar
      epidural and subdural abscesses and the other with osteomyelitis and discitis of
      the spine. Switching from vancomycin to daptomycin plus rifampin-based therapy
      resulted in patient improvement that allowed discharge from the hospital.
      RESULTS: Both patients recovered fully from their infection. CONCLUSIONS:
      Daptomycin is a safe and effective option for the treatment of MRSA infection
      involving the spine.

PMID- 19112050
TI  - A sensitive estimation of residual ethylene glycol in ethylene oxide sterilized
      medical devices by HPLC with electrospray ionization mass spectrometric
      detection.
AB  - A novel analytical methodology for the estimation of residual ethylene glycol
      (EG) in ethylene oxide sterilized polymer is reported. The method involves the
      monitoring of ammonium adduct of EG ions in the presence of 10 mM ammonium
      acetate buffer and methanol using electrospray ionization liquid chromatography
      and mass spectrometry (LC-ESI-MS). The method enables the detection and
      quantification of EG without prior derivatization up to a level of 0.06
      microg/ml. The potentiality of the method is demonstrated by estimating EG in
      ethylene oxide (EtO) sterilized polyethylene terephthalate fabric used in heart
      valve sewing ring. The method is simple, rapid and can routinely be used for the
      quantification of residual EG in EtO sterilized medical devices.

PMID- 19112051
TI  - Development and validation of a hydrophilic interaction liquid chromatography
      tandem mass spectrometry method for determination of isoniazid in human plasma.
AB  - An LC-MS/MS method for the determination of isoniazid in human plasma was
      developed and validated. Human plasma aliquots of 100 microL were used for
      analysis. The assay used nialamide as the internal standard. The calibration
      curve concentration range was 50-10,000 ng/mL. Sample preparation utilized
      protein precipitation, and the supernatant was directly injected onto silica
      column without reconstitution. The recovery was over 90% and matrix effect was
      negligible. The method is simple and fast, which is advantageous in respect to
      instability of isoniazid in human plasma and loss on reconstitution due to its
      low molecular weight.

PMID- 19112052
TI  - Peptide mapping of therapeutic monoclonal antibodies: improvements for increased
      speed and fewer artifacts.
AB  - Peptide mapping is a widely utilized technique to characterize monoclonal
      antibodies for the purpose of product identity and is becoming increasing
      important as a stability indicating assay. Many conventional peptide-mapping
      methods are extremely time consuming and yield a map that is wrought with
      processing artifact peaks such as deamidation, carbamylation, and missed
      cleavages. Therefore, this work examines the many common individual sample
      preparation steps of the peptide-mapping procedure for monoclonal antibodies
      including the steps of denaturing, reduction, sample cleanup, digestion, and HPLC
      solvent selection. Improvements in each of these steps are demonstrated that
      greatly help to reduce artifacts and also allow for reduction of overall sample
      preparation time. After evaluating the many different parameters for increased
      speed and fewer artifacts, the sample preparation was reduced from days to hours
      and the resulting peptide map is nearly free of sample or background artifacts.
      Therefore, this peptide map procedure and optimization scheme is an excellent
      tool to further examine real sample changes in a shorter amount of time.

PMID- 19112053
TI  - H. pylori should be eradicated in chronic liver disease patients with peptic
      ulcer.

PMID- 19112054
TI  - Cholangiocarcinoma: estrogen-induced autocrine effects of VEGF on cell
      proliferation.

PMID- 19112055
TI  - Fabrication of HA/TCP scaffolds with a graded and porous structure using a
      camphene-based freeze-casting method.
AB  - A room temperature camphene-based freeze-casting method was used to fabricate
      hydroxyapatite/tricalcium phosphate (HA/TCP) ceramic scaffolds. By varying the
      solid loading of the mixture and the freezing temperature, a range of structures
      with different pore sizes and strength characteristics were achieved. The
      macropore size of the HA/TCP bioceramics was in the range of 100-200 microm, 40
      80 microm and less than 40 microm at solid loadings of 10, 20 and 30 vol.%,
      respectively. The initial level of solid loading played a primary role in the
      resulting porosity of the scaffolds. The porosity decreased from 72.5 to 31.4
      vol.% when the solid loading was increased from 10 to 30 vol.%. This resulted in
      an increase in the compressive strength from 2.3 to 36.4 MPa. The temperature
      gradient, rather than the percentage porosity, influenced the pore size
      distribution. The compressive strength increased from 1.95 to 2.98 MPa when
      samples were prepared at 4 degrees C as opposed to 30 degrees C. The results
      indicated that it was possible to manufacture porous HA/TCP bioceramics, with
      compressive strengths comparable to cancellous bone, using the freeze-casting
      manufacturing technique, which could be of significant clinical interest.

PMID- 19112056
TI  - Communicating the benefits, harms and risks of medical interventions: in
      journals; to patients and public.

PMID- 19112057
TI  - Current indications for laparoscopy in day-case surgery.
AB  - Day-surgery setting allows to combine patients' satisfaction to cost-saving
      policies that seems to be more and more important for a modern hospital
      management. Minimally invasive surgery seems to be the ideal surgical approach
      for day-case procedures since, reducing trauma to a minimal level, allows
      patients to return quick to a normal life with minimal nursing assistance.
      Extensive review of the most recent article has been performed in this article in
      order to define the current evidences that support the use of laparoscopic
      surgery in a day-case setting. Laparoscopic cholecystectomy, anti-reflux
      procedure and hernia repair seems to be justified according to the results of the
      published data. Patients' selection and hospital organization seem to be
      mandatory in order to obtain successful results.

PMID- 19112058
TI  - Compartment syndrome following prolonged surgery for breast reconstruction with
      epidural analgesia.

PMID- 19112060
TI  - Rapid pressure compensation by automated cuff pressure controllers worsens
      sealing in tracheal tubes.
AB  - BACKGROUND: Cyclic redistribution of air within the cuff during respiratory
      pressure changes creates a self-sealing mechanism which allows tracheal sealing,
      despite tracheal airway pressure being above baseline cuff inflation pressure.
      The aim of the present study was to investigate the effect of continuous
      automated cuff pressure regulation on tracheal sealing during cyclic respiratory
      pressure changes. METHODS: In vitro tracheal sealing was studied in four
      different high volume-low pressure (HVLP) tracheal tube cuffs size internal
      diameter 8.0 and 5.0 mm in combination with a conventional pressure manometer and
      two different automated pressure controllers (VBM Cuff Controller; Cuff Pressure
      Control Tracoe). Experiments were performed at 10, 15, 20, and 25 cm H(2)O cuff
      pressure during intermittent positive pressure ventilation with peak inspiratory
      pressures of 20 and 25 cm H(2)O. Air leakage was assessed spirometrically.
      Experiments were performed four times with each tube brand and size with two
      exemplars of each of the three cuff pressure controllers. RESULTS: Owing to
      immediate cuff pressure correction, tracheal sealing at cuff pressure below
      inspiratory pressure was reduced in most of the tracheal tube cuffs, except in
      those with reduced sealing characteristics when using the Pressure Control Tracoe
      compared with the conventional pressure manometer and the VBM Cuff Controller.
      Tracheal sealing with the Pressure Control Tracoe comparable with the other two
      devices was only achieved at cuff pressures of 20 and 25 cm H(2)O. CONCLUSIONS:
      Automated cuff pressure controllers with rapid pressure correction interfere with
      the self-sealing mechanism of high sealing HVLP tube cuffs and reduce their
      improved sealing characteristics.

PMID- 19112059
TI  - Facial muscle activity, Response Entropy, and State Entropy indices during
      noxious stimuli in propofol-nitrous oxide or propofol-nitrous oxide-remifentanil
      anaesthesia without neuromuscular block.
AB  - BACKGROUND: Entropy is an anaesthetic EEG monitoring method, calculating two
      numerical parameters: State Entropy (SE, range 0-91) and Response Entropy (RE,
      range 0-100). Low Entropy numbers indicate unconsciousness. SE uses the frequency
      range 0.8-32 Hz, representing predominantly the EEG activity. RE is calculated at
      0.8-47 Hz, consisting of both EEG and facial EMG. RE-SE difference (RE-SE) can
      indicate EMG, reflecting nociception. We studied RE-SE and EMG in patients
      anaesthetized without neuromuscular blockers. METHODS: Thirty-one women were
      studied in propofol-nitrous oxide (P) or propofol-nitrous oxide-remifentanil (PR)
      anaesthesia. Target SE value was 40-60. RE-SE was measured before and after
      endotracheal intubation, and before and after the commencement of surgery. The
      spectral content of the signal was analysed off-line. Appearance of EMG on EEG
      was verified visually. RESULTS: RE, SE, and RE-SE increased during intubation in
      both groups. Elevated RE was followed by increased SE values in most cases. In
      these patients, spectral analysis of the signal revealed increased activity
      starting from low (<20 Hz) frequency area up to the highest measured frequencies.
      This was associated with appearance of EMG in raw signal. No spectral alterations
      or EMG were seen in patients with stable Entropy values. CONCLUSIONS: Increased
      RE is followed by increased SE at nociceptive stimuli in patients not receiving
      neuromuscular blockers. Owing to their overlapping power spectra, the
      contribution of EMG and EEG cannot be accurately separated with frequency
      analysis in the range of 10-40 Hz.

PMID- 19112061
TI  - Plain articaine or prilocaine for spinal anaesthesia in day-case knee
      arthroscopy: a double-blind randomized trial.
AB  - BACKGROUND: Both prilocaine and articaine are short-acting local anaesthetics
      suited for spinal anaesthesia for day-case knee arthroscopy. Articaine is thought
      to have a faster onset and shorter duration of action than prilocaine, although
      no comparative study has been published in the anaesthetic literature. METHODS:
      In this prospective randomized double-blind study, spinal anaesthesia was
      performed in 72 ASA I-II patients undergoing knee arthroscopy with 50 mg of
      either plain prilocaine or plain articaine. The primary outcome variable was
      duration of motor block. Secondary outcomes were onset of sensory and motor
      blocks, maximum spread of the sensory block, time to spontaneous voiding, and
      side-effects. RESULTS: Time to full motor function recovery was shorter after
      articaine than prilocaine [mean (SD) 140 (33) vs 184 (46) min, respectively,
      P<0.001]. Time to spontaneous voiding was shorter after articaine than prilocaine
      [mean (SD) 184 (39) vs 227 (45) min, respectively, P<0.001]. One patient in the
      articaine group reported mild transient neurological symptoms (TNS) limited to
      the first postoperative day, but there were no significant differences in adverse
      effects between the groups. CONCLUSIONS: Spinal anaesthesia with plain articaine
      50 mg resulted in a faster recovery of motor function and earlier spontaneous
      voiding compared with plain prilocaine 50 mg. Surgical anaesthesia was not
      different. The incidence of TNS was low.

PMID- 19112062
TI  - Preoperative embolization of cerebral arteriovenous malformations with onyx.
AB  - BACKGROUND AND PURPOSE: Preoperative embolization facilitates the surgical
      management of complex cerebral arteriovenous malformations (cAVMs). This analysis
      aims to investigate the risks for preoperative cAVM embolization with Onyx.
      MATERIALS AND METHODS: We retrospectively analyzed clinical data of all patients
      who underwent embolization with Onyx as a preoperative treatment of cAVMs at our
      institution since 2005 (US Food and Drug Administration [FDA] approval). Patients
      with arteriovenous fistulas were excluded. A total of 107 patients were treated
      for cAVMs during the study period. Of those patients, 41 underwent cAVM
      embolizations with Onyx in 82 procedures. RESULTS: After the embolization, the
      cAVM diameter was reduced from 3.71 +/- 1.55 cm to 3.06 +/- 1.89 cm (P < .05).
      Median volume reduction was 75%. Complete occlusion with embolization alone was
      achieved in 4 (10%) cAVMs. The recurrence rate for completely occluded cAVMs was
      50% (2 patients). A total of 71% of the 41 patients treated with Onyx underwent
      surgery, and 15% underwent radiosurgery. There were 9% who have not yet received
      definitive treatment of their residual cAVMs. A new permanent neurologic deficit
      occurred in 5 patients (6.1% per procedure or 12.2% per patient). CONCLUSIONS: A
      considerable risk for a permanent neurologic deficit remains for cAVM
      embolization with Onyx. The risk has to be carefully weighted against the benefit
      of volume reduction in the treatment of cAVMs.

PMID- 19112063
TI  - Abnormal basiocciput development in CHARGE syndrome.
AB  - BACKGROUND AND PURPOSE: The causative gene of the common congenital malformation
      referred to as CHARGE syndrome is CHD7. Affected individuals often undergo head
      and neck imaging to assess abnormalities of the olfactory structures,
      hypothalamus-pituitary axis, and inner ear. We encountered a few children with
      severe hypoplasia of the basiocciput during a radiologic assessment of patients
      with CHARGE syndrome. To our knowledge, this anomaly has not been reported. Our
      purpose was to evaluate the incidence and severity of this anomaly in this
      syndrome. MATERIALS AND METHODS: Sagittal MR images of 8 patients with CHARGE
      syndrome were retrospectively reviewed by 2 radiologists who consensually
      evaluated the status of the basiocciput of the patients with CHARGE syndrome, as
      either normal or hypoplastic; and associated anomalies, which include basilar
      invagination, Chiari type I malformation, and syringomyelia, as either present or
      absent. The length between the basion (Ba) and the endo-sphenobasion (Es) and
      between the basion and the exo-sphenobasion (Xs) was measured on midsagittal MR
      images of the 8 patients and 70 age-matched controls. We searched for trends
      related to age in the length of Ba-Es and Ba-Xs of the control children by using
      a matched t test. RESULTS: Basioccipital hypoplasia was identified in 7 of the 8
      patients with CHARGE syndrome and was severe in 6. Of those, 5 had associated
      basilar invagination and 1 had Chiari type I malformation with syringomyelia.
      CONCLUSIONS: Basioccipital hypoplasia and basilar invagination are prevalent in
      patients with CHARGE syndrome.

PMID- 19112064
TI  - Characterizing the mesencephalon using susceptibility-weighted imaging.
AB  - BACKGROUND AND PURPOSE: The mesencephalon is involved in a number of human
      neurodegenerative disorders and has been typically imaged with T1-, T2- and T2*
      weighted methods. Our aim was to collect high-contrast susceptibility-weighted
      imaging (SWI) data to differentiate among and within the basic mesencephalic
      structures: namely, the red nucleus, substantia nigra, and crus cerebri.
      MATERIALS AND METHODS: High-resolution SWI, 3D T1-weighted, and T2-weighted data
      were collected to study contrast in the mesencephalon at 1.5T and 4T. Contrast
      between structures was calculated for SWI high-pass (HP)-filtered-phase, T1
      gradient-echo, and spin-echo T2-weighted data. RESULTS: SWI HP-filtered-phase
      data revealed similar contrast for the red nucleus and substantia nigra when
      compared with T2-weighted imaging. However, SWI was able to show structures
      within the red nucleus, substantia nigra, and medial geniculate body that were
      invisible on T2-weighted imaging. T1-weighted imaging, on the other hand, did not
      reveal measurable contrast for any of the structures of interest. SWI HP-filtered
      phase data at 4T agreed well with india ink-stained cadaver brain studies, which
      appear to correlate with capillary density. CONCLUSIONS: With SWI, it is possible
      to create better anatomic images of the mesencephalon, with improved contrast
      compared with conventional T1- or T2-weighted sequences.

PMID- 19112065
TI  - Fully-automated quantification of regional brain volumes for improved detection
      of focal atrophy in Alzheimer disease.
AB  - Volumetric analysis of structural MR images of the brain may provide quantitative
      evidence of neurodegeneration and help identify patients at risk for rapid
      clinical deterioration. This note describes tests of a fully automated MR imaging
      postprocessing system for volumetric analysis of structures (such as the
      hippocampus) known to be affected in early Alzheimer disease (AD). The system
      yielded results that correlated highly with independent computer-aided manual
      segmentation and were sensitive to the anatomic atrophy characteristic of mild
      AD.

PMID- 19112066
TI  - Attenuation of brain white matter hyperintensities after cerebral infarction.

PMID- 19112068
TI  - Optimal preoperative imaging of spinal cord blood supply.

PMID- 19112067
TI  - Temporoparietal MR imaging measures of atrophy in subjects with mild cognitive
      impairment that predict subsequent diagnosis of Alzheimer disease.
AB  - BACKGROUND AND PURPOSE: Mild cognitive impairment (MCI) represents a transitional
      state between normal aging and Alzheimer disease (AD). Our goal was to determine
      if specific temporoparietal regions can predict the time to progress from MCI to
      AD. MATERIALS AND METHODS: MR images from 129 individuals with MCI were analyzed
      to identify the volume of 14 neocortical and 2 non-neocortical brain regions,
      comprising the temporal and parietal lobes. In addition, 3 neuropsychological
      test scores were included to determine whether they would provide independent
      information. After a mean follow-up time of 5 years, 44 of these individuals had
      progressed to a diagnosis of AD. RESULTS: Cox proportional hazards models
      demonstrated significant effects for 6 MR imaging regions with the greatest
      differences being the following: the entorhinal cortex (hazard ratio [HR] = 0.54,
      P < .001), inferior parietal lobule (hazard ratio [HR] = 0.64, P < .005), and
      middle temporal gyrus (HR = 0.64, P < .004), indicating decreased risk with
      larger volumes. A multivariable model showed that a combination of the entorhinal
      cortex (HR = 0.60, P < .001) and the inferior parietal lobule (HR = 0.62, P <
      .01) was the best predictor of time to progress to AD. A multivariable model
      reiterated the importance of including both MR imaging and neuropsychological
      variables in the final model. CONCLUSIONS: These findings reaffirm the importance
      of the entorhinal cortex and present evidence for the importance of the inferior
      parietal lobule as a predictor of time to progress from MCI to AD. The inclusion
      of neuropsychological performance in the final model continues to highlight the
      importance of using these measures in a complementary fashion.

PMID- 19112069
TI  - Salivary gland anlage tumor in a neonate presenting with respiratory distress:
      radiographic and pathologic correlation.
AB  - We present a case of congenital salivary gland anlage tumor (SGAT) of the nasal
      septum in a 2-week-old infant who had difficulty breathing through her nose since
      birth. CT and MR imaging demonstrated a circumscribed mass within the nasal
      cavity that did not communicate with the intracranial compartment. Differential
      diagnosis and clinical significance of recognizing this rare lesion are reviewed.

PMID- 19112070
TI  - Reviewing manuscripts for the American Journal of Neuroradiology:
      responsibilities, challenges, and rewards.

PMID- 19112071
TI  - How to do (or not to do) ... Designing a discrete choice experiment for
      application in a low-income country.
AB  - Understanding the preferences of patients and health professionals is useful for
      health policy and planning. Discrete choice experiments (DCEs) are a quantitative
      technique for eliciting preferences that can be used in the absence of revealed
      preference data. The method involves asking individuals to state their preference
      over hypothetical alternative scenarios, goods or services. Each alternative is
      described by several attributes and the responses are used to determine whether
      preferences are significantly influenced by the attributes and also their
      relative importance. DCEs are widely used in high-income contexts and are
      increasingly being applied in low- and middle-income countries to consider a
      range of policy concerns. This paper aims to provide an introduction to DCEs for
      policy-makers and researchers with little knowledge of the technique. We outline
      the stages involved in undertaking a DCE, with an emphasis on the design
      considerations applicable in a low-income setting.

PMID- 19112072
TI  - Hybrid right-left cardiac resynchronization therapy defibrillator implantation in
      persistent left superior vena cava.
AB  - Persistence of the left superior vena cava (PLSVC), observed in 0.3% of the
      general population as established by autopsy, is an anatomic variation
      particularly relevant when occurring in patients in need of a transvenous pacing.
      In this report, we describe a hybrid right-left cardiac resynchronization therapy
      defibrillator implantation approach in a patient with PLSVC. In our experience,
      the described approach proved feasible and safe, and may be considered an option
      in case of complex vein anatomy before referring for cardiac surgical
      implantation of a left ventricular lead.

PMID- 19112074
TI  - Capture-recapture estimates of the local prevalence of problem drug use in six
      French cities.
AB  - BACKGROUND: General population surveys do not provide reliable estimates of
      problem drug users, which are essential for drug use prevention and treatment
      policies. Indirect estimation methods, especially capture-recapture method, are
      preferred. Problem drug use receives now a growing interest on a European level.
      Very few studies using this method have been carried out in France especially on
      a multicentric level. METHOD: Six three-sample capture-recapture analyses were
      carried out in urban areas of Lille, Lyon, Marseille, Metz, Rennes, Toulouse.
      Data were collected in 2006 from different sources including treatment data, harm
      reduction and social data and law enforcement data. Users of opiates,
      cocaine/crack, stimulants and/or hallucinogens aged 15-64 were identified. Log
      linear models were fitted to the data in order to test different interactions
      between the data sources representing potential dependencies. The simplest model
      was selected on the basis of its Akaike Information Criterion (AIC) and log
      likelihood ratio tests. Confidence intervals were estimated using the likelihood
      interval method. RESULTS: The total number of problem drug users was estimated to
      be 7900 (95% CI 6300-10 200) in Lille, 8400 (6300-11 800) in Lyon, 5600 (4200
      7700) in Marseille, 2300 (1700-3200) in Metz, 1500 (1100-2300) in Rennes and 5400
      (4300-6900) in Toulouse (estimates are rounded to nearest 100). These figures
      correspond to the following prevalence rates of the population aged 15-64 years:
      10.8 per thousand (8.6-14.0) in Lille, 10.6 (8.0-15.0) in Lyon, 10.3 (7.7-14.2)
      in Marseille, 10.8 (8.0-15.0) in Metz, 7.6 (5.6-11.7) in Rennes, 10.1 (8.0-12.9)
      in Toulouse. CONCLUSIONS: Although the confidence intervals are wide, the method
      provides valuable information on the extent of problem drug use.

PMID- 19112073
TI  - Integration of alcohol use disorders identification and management in the
      tuberculosis programme in Tomsk Oblast, Russia.
AB  - Alcohol use disorders (AUDs) among tuberculosis (TB) patients are associated with
      nonadherence and poor treatment outcomes. We developed a multidisciplinary model
      to manage AUDs among TB patients in Tomsk, Russia. First, we assessed current
      standards of care through stakeholder meetings and ethnographic work. The Alcohol
      Use Disorders Identification Test (AUDIT) was incorporated into routine
      assessment of all patients starting TB treatment. We established treatment
      algorithms based on AUDIT scores. We then hired specialists and addressed
      licensing requirements to provide on-site addictions care. Our experience offers
      a successful model in the management of co-occurring AUDs among patients with
      chronic medical problems.

PMID- 19112075
TI  - Epidemiology and cost of treatment of genital warts in Spain.
AB  - BACKGROUND: Genital warts (GW) are common and increasing in young people. Ninety
      percent of GW are due to Human Papillomavirus (HPV) types 6 and 11. The objective
      of this study was to assess the epidemiology and management costs associated with
      GW in Spain. METHODS: A 1-year (2005) retrospective observational study was
      performed among a sample of gynaecologists, dermatologists and urologists in six
      autonomous regions in Spain. Men and women with newly diagnosed, recurrent or
      resistant GW were included. We estimated the incidence (new and recurrent cases)
      and prevalence (also including resistant cases) of GW. Healthcare resource use
      were collected and combined with unit costs to assess the mean cost of GW
      management per patient. These figures were extrapolated to the 14- to 64-year-old
      Spanish population to estimate the total cost of GW management from the Third
      Party Payer (TPP) and societal perspectives. RESULTS: The overall annual
      incidence of GW was estimated at 160.4 cases per 100,000. Overall prevalence was
      calculated as 182.1 cases per 100,000, corresponding to 56 446 GW cases annually
      (14- to 64-year-old population). The mean management cost was 833 euros and 1056
      euro per patient from the TPP and societal perspective, respectively. The overall
      annual cost was estimated at 47 million euros and 59.6 million euros, from the
      TPP and societal perspective, respectively. CONCLUSION: This study provides a
      first overview of the burden of GW in Spain. A quadrivalent HPV vaccine that
      prevents HPV 6, 11, 16, 18 related diseases will have the potential to
      significantly decrease the socio-economic burden associated with GW in Spain.

PMID- 19112076
TI  - Opinion about reproductive decision making among individuals undergoing BRCA1/2
      genetic testing in a multicentre Spanish cohort.
AB  - BACKGROUND: Mutations in breast cancer BRCA1/2 genes increase breast and ovarian
      cancer risk and are transmitted with an autosomal dominant pattern. Opinion about
      reproductive decisions among individuals undergoing BRCA1/2 testing in our
      institutions is unknown. MATERIALS AND METHODS: Individuals (n = 77) undergoing
      BRCA1/2 testing were included in a prospective multicentre study to assess the
      clinical impact of genetic testing. Demographic and clinical information,
      psychological status and opinion about reproductive decisions were collected in
      two questionnaires administered prior to testing. Opinion regarding the use of
      assisted reproduction techniques for hereditary cancer susceptibility among
      health care professionals was also collected. RESULTS: Twenty-eight individuals
      (36%) reported that they would decide to have children, regardless of their
      result. In case of a mutation, 9 (12%) believed that they would decide not to
      have children, 42 (55%) would consider prenatal diagnosis (PND), 37 (48%) would
      consider preimplantation genetic diagnosis (PGD) and 23 (30%) would consider
      adoption. Fifty-seven (74%) and 47 (61%) reported that they considered it ethical
      to offer PND or PGD, respectively, to BRCA+ patients. Individuals older than 40
      years were more likely to consider PND or PGD than younger subjects (P = 0.02 and
      0.05, respectively). Individuals with cancer compared with those without a
      diagnosis of malignancy were more likely to consider PGD (61 versus 30%, P =
      0.02) and to consider that it was ethical to offer it (74 versus 44%, P = 0.02).
      Most health care professionals were in favour of PND and PGD for individuals with
      hereditary cancer susceptibility (58 and 61%, respectively). CONCLUSIONS: BRCA1/2
      genetic results could influence an individual's decisions regarding reproduction.
      Health care professionals who serve individuals undergoing BRCA testing should
      incorporate patient education regarding the potential impact of such testing on
      family planning.

PMID- 19112077
TI  - Collaborative involvement of primary and secondary caregivers: associations with
      youths' diabetes outcomes.
AB  - OBJECTIVE: Collaboration between youths with type 1 diabetes (T1D) and their
      adult caregivers may be central to effective management of T1D. This article
      includes analysis of cross-sectional associations between T1D outcomes
      (adherence, glycemic control, quality of life, family conflict, depression, and
      self-efficacy) and scores on the Collaborative Parent Involvement (CPI) Scale
      obtained from 309 youths with T1D about their primary and secondary caregivers.
      METHODS: MANCOVA, controlling for age, evaluated associations of diabetes
      outcomes with youths' CPI scores for each caregiver. RESULTS: Diabetes outcomes
      were poor when both caregivers obtained CPI scores below the median. Diabetes
      outcomes were more strongly associated with CPI scores of primary, rather than
      secondary, caregivers. CPI scores at or above the median among primary caregivers
      were associated with more favorable status on multiple youth outcomes. When both
      caregivers obtained CPI scores at or above the median, children had significantly
      lower HbA1C and parents retained more responsibility for diabetes care.
      CONCLUSIONS: Higher collaborative involvement, particularly among primary
      caregivers, was associated with favorable status along a variety of diabetes
      outcomes. Longitudinal studies could confirm if youth-parent collaboration is a
      justifiable intervention target.

PMID- 19112079
TI  - Antisense inhibition of the PsbX protein affects PSII integrity in the higher
      plant Arabidopsis thaliana.
AB  - PSII, the oxygen-evolving complex of photosynthetic organisms, contains an
      intriguingly large number of low molecular weight proteins. PsbX, one of these
      proteins, is ubiquitous in PSII complexes of cyanobacteria and plants. In
      previous studies, deletion of the PsbX protein in cyanobacteria has not resulted
      in clear phenotypic changes. Here we report the construction of an antisense (AS
      PsbX) line in Arabidopsis thaliana with <10% of wild-type PsbX levels. AS-PsbX
      plants are capable of photoautotrophic growth, but biochemical, biophysical and
      immunological evidence demonstrates that reduction of PsbX contents leads to
      reduced levels of functional assembled PSII core complexes, while the light
      harvesting antennae are not affected. In addition, levels of phosphorylation of
      the core proteins D1, D2 and CP43 are severely reduced in the antisense plants
      relative to their wild-type counterparts. We conclude that PsbX is important for
      accumulation of functional PSII.

PMID- 19112078
TI  - Single-molecule detection of folding and unfolding of the G-quadruplex aptamer in
      a nanopore nanocavity.
AB  - Guanine-rich nucleic acids can form G-quadruplexes that are important in gene
      regulation, biosensor design and nano-structure construction. In this article, we
      report on the development of a nanopore encapsulating single-molecule method for
      exploring how cations regulate the folding and unfolding of the G-quadruplex
      formed by the thrombin-binding aptamer (TBA, GGTTGGTGTGGTTGG). The signature
      blocks in the nanopore revealed that the G-quadruplex formation is cation
      selective. The selectivity sequence is K(+) > NH(4)(+) approximately Ba(2+) >
      Cs(+) approximately Na(+) > Li(+), and G-quadruplex was not detected in Mg(2+)
      and Ca(2+). Ba(2+) can form a long-lived G-quadruplex with TBA. However, the
      capability is affected by the cation-DNA interaction. The cation-selective
      formation of the G-quadruplex is correlated with the G-quadruplex volume, which
      varies with cation species. The high formation capability of the K(+)-induced G
      quadruplex is contributed largely by the slow unfolding reaction. Although the
      Na(+)- and Li(+)-quadruplexes feature similar equilibrium properties, they
      undergo radically different pathways. The Na(+)-quadruplex folds and unfolds most
      rapidly, while the Li(+)-quadruplex performs both reactions at the slowest rates.
      Understanding these ion-regulated properties of oligonucleotides is beneficial
      for constructing fine-tuned biosensors and nano-structures. The methodology in
      this work can be used for studying other quadruplexes and protein-aptamer
      interactions.

PMID- 19112080
TI  - Involvement of reactive nitrogen and oxygen species (RNS and ROS) in sunflower
      mildew interaction.
AB  - Nitric oxide (.NO) has been shown to participate in plant response against
      pathogen infection; however, less is known of the participation of other NO
      derived molecules designated as reactive nitrogen species (RNS). Using two
      sunflower (Helianthus annuus L.) cultivars with different sensitivity to
      infection by the pathogen Plasmopara halstedii, we studied key components
      involved in RNS and ROS metabolism. We analyzed the superoxide radical
      production, hydrogen peroxide content, l-arginine-dependent nitric oxide synthase
      (NOS) and S-nitrosoglutathione reductase (GSNOR) activities. Furthermore, we
      examined the location and contents of .NO, S-nitrosothiols (RSNOs), S
      nitrosoglutathione (GSNO) and protein 3-nitrotyrosine (NO(2)-Tyr) by confocal
      laser scanning microscopy (CLSM) and biochemical analyses. In the susceptible
      cultivar, the pathogen induces an increase in proteins that undergo tyrosine
      nitration accompanied by an augmentation in RSNOs. This rise of RSNOs seems to be
      independent of the enzymatic generation of .NO because the l-arginine-dependent
      NOS activity is reduced after infection. These results suggest that pathogens
      induce nitrosative stress in susceptible cultivars. In contrast, in the resistant
      cultivar, no increase of RSNOs or tyrosine nitration of proteins was observed,
      implying an absence of nitrosative stress. Therefore, it is proposed that the
      increase of tyrosine nitration of proteins can be considered a general biological
      marker of nitrosative stress in plants under biotic conditions.

PMID- 19112081
TI  - Differential dependency network analysis to identify condition-specific
      topological changes in biological networks.
AB  - MOTIVATION: Significant efforts have been made to acquire data under different
      conditions and to construct static networks that can explain various gene
      regulation mechanisms. However, gene regulatory networks are dynamic and
      condition-specific; under different conditions, networks exhibit different
      regulation patterns accompanied by different transcriptional network topologies.
      Thus, an investigation on the topological changes in transcriptional networks can
      facilitate the understanding of cell development or provide novel insights into
      the pathophysiology of certain diseases, and help identify the key genetic
      players that could serve as biomarkers or drug targets. RESULTS: Here, we report
      a differential dependency network (DDN) analysis to detect statistically
      significant topological changes in the transcriptional networks between two
      biological conditions. We propose a local dependency model to represent the local
      structures of a network by a set of conditional probabilities. We develop an
      efficient learning algorithm to learn the local dependency model using the Lasso
      technique. A permutation test is subsequently performed to estimate the
      statistical significance of each learned local structure. In testing on a
      simulation dataset, the proposed algorithm accurately detected all the genes with
      network topological changes. The method was then applied to the estrogen
      dependent T-47D estrogen receptor-positive (ER+) breast cancer cell line datasets
      and human and mouse embryonic stem cell datasets. In both experiments using real
      microarray datasets, the proposed method produced biologically meaningful
      results. We expect DDN to emerge as an important bioinformatics tool in
      transcriptional network analyses. While we focus specifically on transcriptional
      networks, the DDN method we introduce here is generally applicable to other
      biological networks with similar characteristics. AVAILABILITY: The DDN MATLAB
      toolbox and experiment data are available at
      http://www.cbil.ece.vt.edu/software.htm.

PMID- 19112082
TI  - Solutions for data integration in functional genomics: a critical assessment and
      case study.
AB  - The torrent of data emerging from the application of new technologies to
      functional genomics and systems biology can no longer be contained within the
      traditional modes of data sharing and publication with the consequence that data
      is being deposited in, distributed across and disseminated through an increasing
      number of databases. The resulting fragmentation poses serious problems for the
      model organism community which increasingly rely on data mining and computational
      approaches that require gathering of data from a range of sources. In the light
      of these problems, the European Commission has funded a coordination action,
      CASIMIR (coordination and sustainability of international mouse informatics
      resources), with a remit to assess the technical and social aspects of database
      interoperability that currently prevent the full realization of the potential of
      data integration in mouse functional genomics. In this article, we assess the
      current problems with interoperability, with particular reference to mouse
      functional genomics, and critically review the technologies that can be deployed
      to overcome them. We describe a typical use-case where an investigator wishes to
      gather data on variation, genomic context and metabolic pathway involvement for
      genes discovered in a genome-wide screen. We go on to develop an automated
      approach involving an in silico experimental workflow tool, Taverna, using web
      services, BioMart and MOLGENIS technologies for data retrieval. Finally, we focus
      on the current impediments to adopting such an approach in a wider context, and
      strategies to overcome them.

PMID- 19112083
TI  - Activity of vancomycin against epidemic Clostridium difficile strains in a human
      gut model.
AB  - OBJECTIVES: Vancomycin and metronidazole remain the only primary options for the
      treatment of Clostridium difficile infection (CDI). Recent reports have suggested
      a superior clinical response to vancomycin therapy compared with metronidazole,
      but this has been difficult to prove or explain. There are few robust in vitro
      data of the effects of antibiotic treatment of CDI in a gut reflective setting.
      METHODS: We used clindamycin to induce high-level toxin production by two
      epidemic C. difficile PCR ribotypes in a human gut model of CDI. Vancomycin was
      instilled into the models to achieve in vivo faecal concentrations. C. difficile
      populations and toxin titres, and gut bacterial populations and vancomycin levels
      were monitored before, during and after vancomycin instillation. RESULTS:
      Clindamycin treatment elicited C. difficile germination and high-level cytotoxin
      production. Vancomycin reduced total viable counts and cytotoxin titres of both
      C. difficile PCR ribotypes, with no evidence of recurrence before the model runs
      were ended. C. difficile PCR ribotype 027 populations exhibited greater
      germination capacity than did PCR ribotype 106. Vancomycin was more rapidly
      effective against the greater numbers of PCR ribotype 027 vegetative forms.
      Vancomycin showed no activity against C. difficile spores. CONCLUSIONS:
      Bacteriological response to vancomycin varies between strains causing CDI,
      possibly correlating with the extent of germination capacity. Vancomycin
      effectively reduced vegetative forms and cytotoxin titres of both of the epidemic
      C. difficile PCR ribotypes evaluated, but showed no anti-spore activity.
      Comparison with the results of a previous gut model study showed that vancomycin
      was more effective than metronidazole in reducing C. difficile PCR ribotype 027
      numbers and cytotoxin titres.

PMID- 19112085
TI  - Longitudinal changes in GPs' task perceptions, self-efficacy, barriers and
      practices of nutrition education and treatment of overweight.
AB  - BACKGROUND: GPs play a role in prevention by giving nutrition education and
      advice on overweight. Over the years, GP's tasks and working environment changed.
      OBJECTIVE: To know how task perceptions, perceptions of own ability and perceived
      barriers regarding nutrition education and treatment of overweight of Dutch GPs
      have developed from 1992 to 2007. METHODS: In all, 488 GPs, first included in
      study in 1992, were asked in 2007 to return the Wageningen PCPs Nutritional
      Practices Questionnaire. Crohnbach's alphas and sum scores were calculated and
      differences between 1992 and 2007 were investigated using a paired t-test.
      RESULTS: In all, 247 GPs responded (51%). 'Noticing patients overweight and
      guidance of treatment' did not change in GPs from 1992 to 2007. The task
      perception about health education and prevention did not change and the
      perception of daily activities shifted from the curative to the preventive side.
      Interest in the influence of nutrition on health increased in 2007. GPs less
      often managed to counsel on nutrition in daily practice. Their perceived capacity
      to counsel and their self-efficacy regarding overweight management declined over
      the years. In 2007, more GPs perceived the barriers 'lack of time' to treat
      overweight and to give nutrition education. The most important barrier in 2007
      was lack of patient motivation. CONCLUSIONS: The GPs perceived overweight and
      nutrition education as important and were still favourable towards prevention.
      However, their potential to give nutrition education or guide in treatment of
      overweight was not fully utilized because of decreased self-efficacy factors and
      perceived barriers.

PMID- 19112086
TI  - Nutrition care for adult cardiac patients: Australian general practitioners'
      perceptions of their roles.
AB  - BACKGROUND: Australia has implemented systematic managed care for patients with
      chronic disease. Little is known about how GPs perceive their nutrition care role
      in this system. OBJECTIVE: To examine GPs' perceptions of their roles in the
      nutrition care of cardiac patients and to identify factors that influence their
      role. METHODS: Multi-methods research design. Semi-structured interviews were
      conducted with a sample (n = 30) GPs Victoria, Australia. The resulting
      narratives were used to develop a quantitative questionnaire to survey a random
      sample of GPs. Principal components analysis was conducted to reduce the role
      items to a small number of underlying dimensions. The association between roles
      and demographic variables were examined using stepwise multiple regressions.
      RESULTS: In all, 248 GPs (30% response) participated. Three main roles were
      established: Influencing, Coordinating and Nutrition Educator role. Together, the
      roles explained 54% of the total variance. Demographic variables were not
      associated with these roles. The majority (mean = 88%) endorsed the items which
      loaded on to the Influencing and Coordinating (mean = 49%) roles. Short
      consultation time, use of prescribed medications and perception of patient
      attendance at cardiac rehabilitation reduced the priority for nutrition
      education. CONCLUSIONS: This study highlights the importance of developing more
      effective team care arrangements for patients with chronic disease and working
      with the medical education colleges to develop education resources for doctors
      that include an explanation of the non-pharmaceutical as well as the
      pharmaceutical treatment for each chronic disease condition.

PMID- 19112087
TI  - The public health view on closing the gap between public health and primary care.
AB  - This paper outlines the public health issues relating to the north-west region of
      England. The role of Primary Care Trusts in addressing the health and well-being
      issues is described and the development of Teaching Public Health Networks to
      support capacity and capability building in the public health workforce is
      outlined. Healthy weight management is used as a case study of how public health
      and primary care can be brought closer together by describing the role of the
      Food and Health Action Plan in addressing healthy weight management and its
      relationship with primary care.

PMID- 19112090
TI  - Creating supportive environments for nutrition guidance: towards a synergy
      between Primary Care and Public Health.

PMID- 19112091
TI  - Retinoic acid regulates Fas-induced apoptosis in Jurkat T cells: reversal of
      mitogen-mediated repression of Fas DISC assembly.
AB  - The effect of the immune regulator vitamin A on T cell death has been poorly
      characterized. In the present study, we demonstrate that an active metabolite of
      vitamin A, retinoic acid (RA), promotes cell death in Jurkat leukemic T cells by
      counteracting mitogen-mediated repression of Fas-induced apoptosis. The effect of
      RA was dose-dependent, and at the optimal concentration of 1 muM, repression of
      Fas-induced cell death by the mitogens 12-O-tetradecanoylphorbol 13-acetate (TPA)
      or Con A was reversed by approximately 50% and 30%, respectively. RA promoted
      apoptosis rather than necrosis, as judged by analysis of cell morphology,
      mitochondrial membrane depolarization, and DNA fragmentation. TPA-mediated
      protection from Fas-induced apoptosis is dependent on ERK and NF-kappaB. However,
      analyses of ERK and NF-kappaB activities and expression of target genes indicated
      that RA-mediated counteraction of the protective effect of TPA did not involve
      negative crosstalk with ERK or NF-kappaB survival pathways. RA-induced cell death
      was accompanied by enhanced cleavage of procaspase-3, -6, and -8, as well as
      enhanced cleavage of DNA fragmentation factor 45. Interestingly, RA-mediated
      cleavage of procaspase-8 occurred very early and before any effect of RA could be
      detected on procaspase-3 cleavage, suggesting that RA might act at the level of
      the Fas death-inducing signaling complex (DISC). Indeed, DISC immunoprecipitation
      studies revealed that RA treatment reversed the inhibitory effect of TPA on CH11
      induced recruitment and processing of procaspase-8 at the DISC. In conclusion, we
      have identified a role of RA in abrogating mitogen-mediated repression of Fas
      DISC assembly, thus enhancing Fas-induced apoptosis in leukemic T cells.

PMID- 19112092
TI  - Allo-restricted CTLs generated by coculturing of PBLs and autologous monocytes
      loaded with allogeneic peptide/HLA/IgG1-Fc fusion protein.
AB  - The graft-versus-leukemia effect of allogeneic marrow transplantation suggests
      the dramatic effect of the allogeneic T cell to eradicate malignant disease.
      Preparation and adoptive transfusion of tumor-specific T cells from HLA
      mismatched donors might be expected to circumvent CTL tolerance to the tumor. In
      this study, a soluble, divalent HLA-A2 molecule was constructed with the Fc part
      of human IgG1 and was pulsed with a peptide related to melanoma tyrosinase 368
      376 [Tyr(368-376) (Tyr)] to form the Tyr/HLA-A2 dimer, which allowed loading onto
      monocytes via interaction of the Fc and FcR. The HLA-A2-negative (HLA-A2-ve)
      monocytes loaded with the Tyr/HLA-A2 dimer acted as allo-APC with copies of a
      single allogeneic epitope. After coculture of the HLA-A2-ve PBLs and autologous
      monocytes loaded with the dimer, CD8+ cells in the coculture show an obvious
      proliferation and increased frequency of Tyr/HLA-A2 tetramer-stained cells. The
      sorted Tyr/HLA-A2 tetramer-positive CD8+ cells display an elevated cytotoxic
      activity against HLA-A2-positive melanoma cells expressing tyrosinase
      endogenously (i.e., SK-Mel-5) but little against tyrosinase-negative melanoma
      cells (i.e., A375). The coculture of PBLs and autologous monocytes loaded with
      allogeneic peptide/HLA complexes offers a novel approach to expand allo
      restricted, peptide-specific CTLs, which might be a potential arsenal for
      treatment of patients with malignant disease, if the tumor-related epitope were
      defined.

PMID- 19112093
TI  - Pivotal Advance: Toll-like receptor regulation of scavenger receptor-A-mediated
      phagocytosis.
AB  - Class-A scavenger receptors (SR-A) and TLR mediate early immune responses against
      pathogenic bacteria. SR-A and TLR molecules are expressed on phagocytes and
      interact with common ligands from Gram-negative and Gram-positive bacteria;
      however, the contribution of TLR activity to SR-A-mediated phagocytosis has not
      been assessed directly. Herein, we provide genetic and functional evidence that
      ligand- and TLR-specific stimuli synergize with SR-A to mediate bacterial
      phagocytosis. Although complete loss of SR-A (SR-A(-/-)) is known to impair
      bacterial clearance, here we identify the first deficiency attributable to SR-A
      heterozygosity: SR-A(+/-)TLR4(+/-) cells and mice are impaired significantly in
      the clearance of Gram-negative Escherichia coli. This phenotype is specific to
      the TLR signaling event, as SR-A(+/-)TLR4(+/-) cells are not deficient for the
      clearance of Gram-positive Staphylococcus aureus bacteria, which contain cell
      surface TLR2 ligands but lack TLR4 ligands. We demonstrate that this is a global,
      phagocytic mechanism, regulated independently by multiple TLRs, as analogous to
      the SR-A(+/-)TLR4(+/-) deficit, SR-A(+/-)TLR2(+/-) cells are impaired for S.
      aureus uptake. In support of this, we show that SR-A(+/-)MyD88(+/-) cells
      recapitulate the phagocytosis defect observed in SR-A(+/-)TLR4(+/-) cells. These
      data identify for the first time that TLR-driven innate immune responses, via a
      MyD88 signaling mechanism, regulate SR-A-dependent phagocytosis of bacteria.
      These findings provide novel insights into how innate immune cells control SR-A
      mediated trafficking and are the first demonstration that subtle changes in the
      expression of SR-A and TLRs can substantially affect host bacterial clearance.

PMID- 19112094
TI  - Gene profiling of left ventricle eccentric hypertrophy in aortic regurgitation in
      rats: rationale for targeting the beta-adrenergic and renin-angiotensin systems.
AB  - Aortic valve regurgitation (AR) imposes a severe volume overload to the left
      ventricle (LV), which results in dilation, eccentric hypertrophy, and eventually
      loss of function. Little is known about the impact of AR on LV gene expression.
      We, therefore, conducted a gene expression profiling study in the LV of rats with
      acute and severe AR. We identified 64 genes that were specifically upregulated
      and 29 that were downregulated out of 21,910 genes after 2 wk. Of the upregulated
      genes, a good proportion was related to the extracellular matrix. We subsequently
      studied a subset of 19 genes by quantitative RT-PCR (qRT-PCR) to see if the
      modulation seen in the LV after 2 wk persisted in the chronic phase (after 6 and
      12 mo) and found that it did persist. Knowing that the adrenergic and renin
      angiotensin systems are overactivated in our animal model, we were interested to
      see if blocking those systems using metoprolol (25 mg.kg(-1).day(-1)) and
      captopril (100 mg.kg(-1).day(-1)) would alter the expression of some upregulated
      LV genes in AR rats after 6 mo. By qRT-PCR, we observed that upregulations of LV
      mRNA levels encoding for procollagens type I and III, fibronectin, atrial
      natriuretic peptide, transforming growth factor-beta(2), and connective tissue
      growth factor were totally or partially reversed by this treatment. These
      observations provide a molecular rationale for a medical strategy aiming these
      systems in the medical treatment of AR and expand the paradigm in the study of
      this form of LV volume overload.

PMID- 19112095
TI  - CD40/CD40L contributes to hypercholesterolemia-induced microvascular
      inflammation.
AB  - Hypercholesterolemia is associated with phenotypic changes in endothelial cell
      function that lead to a proinflammatory and prothrombogenic state in different
      segments of the microvasculature. CD40 ligand (CD40L) and its receptor CD40 are
      ubiquitously expressed and mediate inflammatory responses and platelet
      activation. The objective of this study was to determine whether CD40/CD40L, in
      particular T-cell CD40L, contributes to microvascular dysfunction induced by
      hypercholesterolemia. Intravital microscopy was used to quantify blood cell
      adhesion in cremasteric postcapillary venules, endothelium-dependent vasodilation
      responses in arterioles, and microvascular oxidative stress in wild-type (WT)
      C57BL/6, CD40-deficient ((-/-)), CD40L(-/-), or severe combined immune deficient
      (SCID) mice placed on a normal (ND) or high-cholesterol (HC) diet for 2 wk. WT-HC
      mice exhibited an exaggerated leukocyte and platelet recruitment in venules and
      impaired vasodilation responses in arterioles compared with ND counterparts. A
      deficiency of CD40, CD40L, or lymphocytes attenuated these responses to HC. The
      HC phenotype was rescued in CD40L(-/-) and SCID mice by a transfer of WT T cells.
      Bone marrow chimeras revealed roles for both vascular- and blood cell-derived
      CD40 and CD40L in the HC-induced vascular responses. Hypercholesterolemia induced
      an oxidative stress in both arterioles and venules of WT mice, which was
      abrogated by either CD40 or CD40L deficiency. The transfer of WT T cells into
      CD40L(-/-) mice restored the oxidative stress. These results implicate CD40/CD40L
      interactions between circulating cells and the vascular wall in both the
      arteriolar and venular dysfunction elicited by hypercholesterolemia and identify
      T-cell-associated CD40L as a key mediator of these responses.

PMID- 19112096
TI  - Chronic hypoxia enhances 15-lipoxygenase-mediated vasorelaxation in rabbit
      arteries.
AB  - 15-Lipoxygenase (15-LO-1) metabolizes arachidonic acid (AA) to 11,12,15
      trihydroxyeicosatrienoic acids (THETAs) and 15-hydroxy-11,12-epoxyeicosatrienoic
      acids (HEETA) that dilate rabbit arteries. Increased endothelial 15-LO-1
      expression enhances arterial relaxations to agonists. We tested the effect of
      hypoxia on 15-LO-1 expression, THETA and HEETA synthesis, and relaxations in
      rabbit arteries. The incubation of rabbit aortic endothelial cells and isolated
      aortas in 0.7% O(2) increased 15-LO-1 expression. Rabbits were housed in a
      hypoxic atmosphere of 12% O(2) for 5 days. 15-LO-1 expression increased in the
      endothelium of the arteries of rabbits in 12% O(2) compared with room air. THETA
      and HEETA synthesis was also enhanced in aortas and mesenteric arteries. AA
      hyperpolarized the smooth muscle cells in indomethacin- and phenylephrine-treated
      mesenteric arteries of hypoxic rabbits from -29.4 +/- 1 to -50.1 +/- 3 mV. The
      hyperpolarization to AA was less in arteries of normoxic rabbits (from -26.0 +/-
      2 to -37 +/- 2 mV). This AA-induced hyperpolarization was inhibited by the 15-LO
      inhibitor BW-755C. Nitric oxide and prostaglandin-independent maximum relaxations
      to acetylcholine (79.7 +/- 2%) and AA (38.3 +/- 4%) were enhanced in mesenteric
      arteries from hypoxic rabbits compared with the normoxic rabbits (49.7 +/- 6% and
      19.9 +/- 2%, respectively). These relaxations were inhibited by BW-755C and
      nordihydroguaiaretic acid. Therefore, hypoxia increased the relaxations to
      agonists in the rabbit mesenteric arteries by enhancing endothelial 15-LO-1
      expression and synthesis of the hyperpolarizing factors THETA and HEETA.

PMID- 19112097
TI  - Electrical remodeling in a transgenic mouse model of alpha1B-adrenergic receptor
      overexpression.
AB  - Cardiac-specific overexpression of wild-type alpha(1B)-adrenergic receptors
      (alpha(1B)-AR) in mice predisposes to dilated cardiomyopathy and sudden death.
      Although alpha-adrenergic stimulation is thought to contribute to induction of
      arrhythmias in heart failure, the electrophysiological consequences of chronic
      alpha(1)-adrenergic activation have not been clearly defined. Thus we
      characterized ventricular repolarization and monitored incidence of spontaneous
      arrhythmias in end-stage heart failure alpha(1B)-AR mice (9-12 mo) and younger
      alpha(1B)-AR mice (2-3 mo) that do not present signs of heart failure. Compared
      with aged-matched controls, the corrected QT interval was 34% longer in the 9- to
      12-mo alpha(1B)-AR mice, and the action potential durations were also
      significantly prolonged in these mice. These changes were associated with a
      decrease in the density of the outward K(+) currents, Ca(2+)-independent
      transient, ultrarapid delayed rectifier, and steady state (at +30 mV, reduction
      of 68, 64, and 41%, respectively), and underlying K(+) channel expression.
      Electrocardiogram (ECG) recordings revealed that older alpha(1B)-AR mice
      exhibited spontaneous ventricular arrhythmias. The alterations in repolarization
      can contribute to these rhythm abnormalities and are likely caused by chronic
      alpha(1B)-AR activity. Additional data obtained in 2- to 3-mo alpha(1B)-AR mice
      clearly showed that electrical remodeling was already observed in younger
      transgenic animals. However, it appeared to be slightly less pronounced than in
      older mice. These results suggest that there are two waves of remodeling: one due
      to chronic alpha(1B)-AR activity, and a second due to heart failure. Taken
      together, these data provide strong evidence for a pathological role of chronic
      alpha(1B)-AR activity in the development of repolarization defects and
      ventricular arrhythmias.

PMID- 19112098
TI  - Phospholamban overexpression in rabbit ventricular myocytes does not alter
      sarcoplasmic reticulum Ca transport.
AB  - Phospholamban has been suggested to be a key regulator of cardiac sarcoplasmic
      reticulum (SR) Ca cycling and contractility and a potential therapeutic target in
      restoring the depressed Ca cycling in failing hearts. Our understanding of the
      function of phospholamban stems primarily from studies in genetically altered
      mouse models. To evaluate the significance of this protein in larger mammalian
      species, which exhibit Ca cycling properties similar to humans, we overexpressed
      phospholamban in adult rabbit cardiomyocytes. Adenoviral-mediated gene transfer,
      at high multiplicities of infection, resulted in an insignificant 1.22-fold
      overexpression of phospholamban. There were no effects on twitch Ca-transient
      amplitude or decay under basal or isoproterenol-stimulated conditions.
      Furthermore, the SR Ca load and Na/Ca exchanger function were not altered. These
      apparent differences between phospholamban overexpression in rabbit compared with
      previous findings in the mouse may be due to a significantly higher (1.5-fold)
      endogenous phospholamban-to-sarco(endo)plasmic reticulum Ca-ATPase (SERCA) 2a
      ratio and potential functional saturation of SERCA2a by phospholamban in rabbit
      cardiomyocytes. The findings suggest that important species-dependent differences
      in phospholamban regulation of SERCA2a occur. In larger mammals, a higher
      fraction of SERCA2a pumps are regulated by phospholamban, and this may influence
      therapeutic strategies to enhance cardiac contractility and functional cardiac
      reserve.

PMID- 19112099
TI  - Repeated ethanol exposure during late gestation alters the maturation and innate
      immune status of the ovine fetal lung.
AB  - Little is known about the effects of fetal ethanol exposure on lung development.
      Our aim was to determine the effects of repeated ethanol exposure during late
      gestation on fetal lung growth, maturation, and inflammatory status. Pregnant
      ewes were chronically catheterized at 91 days of gestational age (DGA; term
      approximately 147 days). From 95-133 DGA, ewes were given a 1-h daily infusion of
      either 0.75 g ethanol/kg (n = 9) or saline (n = 8), with tissue collection at 134
      DGA. Fetal lungs were examined for changes in tissue growth, structure,
      maturation, inflammation, and oxidative stress. Between treatment groups, there
      were no differences in lung weight, DNA and protein contents, percent
      proliferating and apoptotic cells, tissue and air-space fractions, alveolar
      number and mean linear intercept, septal thickness, type-II cell number and
      elastin content. Ethanol exposure caused a 75% increase in pulmonary collagen I
      alpha1 mRNA levels (P < 0.05) and a significant increase in collagen deposition.
      Surfactant protein (SP)-A and SP-B mRNA levels were approximately one third of
      control levels following ethanol exposure (P < 0.05). The mRNA levels of the
      proinflammatory cytokines interleukin (IL)-1beta and IL-8 were also lower (P <
      0.05) in ethanol-exposed fetuses compared with controls. Pulmonary
      malondialdehyde levels tended to be increased (P = 0.07) in ethanol-exposed
      fetuses. Daily exposure of the fetus to ethanol during the last third of
      gestation alters extracellular matrix deposition and surfactant protein gene
      expression, which could increase the risk of respiratory distress syndrome after
      birth. Changes to the innate immune status of the fetus could increase the
      susceptibility of the neonatal lungs to infection.

PMID- 19112100
TI  - SARS-CoV proteins decrease levels and activity of human ENaC via activation of
      distinct PKC isoforms.
AB  - Among the multiple organ disorders caused by the severe acute respiratory
      syndrome coronavirus (SARS-CoV), acute lung failure following atypical pneumonia
      is the most serious and often fatal event. We hypothesized that two of the
      hydrophilic structural coronoviral proteins (S and E) would regulate alveolar
      fluid clearance by decreasing the cell surface expression and activity of
      amiloride-sensitive epithelial sodium (Na(+)) channels (ENaC), the rate-limiting
      protein in transepithelial Na(+) vectorial transport across distal lung
      epithelial cells. Coexpression of either S or E protein with human alpha-, beta-,
      and gamma-ENaC in Xenopus oocytes led to significant decreases of both amiloride
      sensitive Na(+) currents and gamma-ENaC protein levels at their plasma membranes.
      S and E proteins decreased the rate of ENaC exocytosis and either had no effect
      (S) or decreased (E) rates of endocytosis. No direct interactions among SARS-CoV
      E protein with either alpha- or gamma-ENaC were indentified. Instead, the
      downregulation of ENaC activity by SARS proteins was partially or completely
      restored by administration of inhibitors of PKCalpha/beta1 and PKCzeta.
      Consistent with the whole cell data, expression of S and E proteins decreased
      ENaC single-channel activity in oocytes, and these effects were partially
      abrogated by PKCalpha/beta1 inhibitors. Finally, transfection of human airway
      epithelial (H441) cells with SARS E protein decreased whole cell amiloride
      sensitive currents. These findings indicate that lung edema in SARS infection may
      be due at least in part to activation of PKC by SARS proteins, leading to
      decreasing levels and activity of ENaC at the apical surfaces of lung epithelial
      cells.

PMID- 19112101
TI  - Role of acylglycerol kinase in LPA-induced IL-8 secretion and transactivation of
      epidermal growth factor-receptor in human bronchial epithelial cells.
AB  - LPA (lysophosphatidic acid) is a potent bioactive phospholipid, which regulates a
      number of diverse cellular responses through G protein-coupled LPA receptors.
      Intracellular LPA is generated by the phosphorylation of monoacylglycerol by
      acylglycerol kinase (AGK); however, the role of intracellular LPA in signaling
      and cellular responses remains to be elucidated. Here, we investigated signaling
      pathways of IL-8 secretion mediated by AGK and intracellular LPA in human
      bronchial epithelial cells (HBEpCs). Expression of AGK in HBEpCs was detected by
      real-time PCR, and overexpressed AGK was mainly localized in mitochondria as
      determined by immunofluorescence and confocal microscopy. Overexpression of
      lentiviral AGK wild type increased intracellular LPA production ( approximately
      1.8-fold), enhanced LPA-mediated IL-8 secretion, and stimulated tyrosine
      phosphorylation epidermal growth factor-receptor (EGF-R). Furthermore,
      downregulation of native AGK by AGK small interfering RNA decreased intracellular
      LPA levels ( approximately 2-fold) and attenuated LPA-induced p38 MAPK, JNK, and
      NF-kappaB activation, tyrosine phosphorylation of EGF-R, and IL-8 secretion.
      These results suggest that native AGK regulates LPA-mediated IL-8 secretion
      involving MAPKs, NF-kappaB, and transactivation of EGF-R. Thus AGK may play an
      important role in innate immunity and airway remodeling during inflammation.

PMID- 19112102
TI  - Adenovirus E1A regulates lung epithelial ICAM-1 expression by interacting with
      transcriptional regulators at its promoter.
AB  - We focused on the regulation of inflammatory mediator expression by adenovirus
      E1A in lung epithelial cells and the role of this viral protein in the
      pathogenesis of chronic obstructive pulmonary disease (COPD). We previously
      reported that E1A, a well-known regulator of host genes, increased ICAM-1
      expression in human bronchial epithelial (HBE) and A549 cells in response to LPS
      stimulation. In this report, we clarified the mechanism of this regulation. We
      found NF-kappaB translocation to the nucleus after LPS stimulation in both E1A
      positive and -negative HBE cells. ICAM-1 promoter reporter constructs revealed
      that a mutation in the proximal NF-kappaB binding site completely inhibited
      increased transcription, whereas the mutation in a distal site did not. We
      analyzed the participation of E1A in transcriptional complex formation at this
      promoter using chromatin immunoprecipitation. In E1A-positive HBE and A549 cells,
      LPS stimulation increased ICAM-1 promoter immunoprecipitation by NF-kappaB p65
      and p300 but not activator protein-1 antibodies with a concomitant increase by
      the E1A antibody. No increase was found in E1A-negative cells except in HBE cells
      with p65 antibody. The association of E1A with the increased promoter
      immunoprecipitation with p300 was also observed after TNF-alpha stimulation of
      A549 cells. These results suggest that adenovirus E1A regulates the ICAM-1
      promoter through its proximal NF-kappaB binding site, most likely by interacting
      with the transcriptional complex that forms at this site. E1A regulation of the
      LPS response may play a role in acute exacerbations as a consequence of bacterial
      infections in COPD.

PMID- 19112103
TI  - Effect of covalent antithrombin-heparin complex on developmental mechanisms in
      the lung.
AB  - We have developed a potent antithrombin (AT)-heparin conjugate (ATH) that is
      retained in the lung to prevent pulmonary thrombosis associated with respiratory
      distress in premature newborns. During continuing maturation, pulmonary
      angiogenesis in premature infants would be a crucial process in lung development.
      A naturally occurring latent form of antithrombin (L-AT) has antiangiogenic
      effects on lung vascularization. However, impact of latent ATH (L-ATH) on
      developing lung vascularization is unknown. Thus, effects of L-AT and L-ATH on
      fetal murine lung development were compared. Lung buds from embryonic day 11.5
      (E11.5) Tie2-LacZ mouse embryos were incubated in DMEM plus FBS supplemented with
      PBS, AT, L-AT, heparin, ATH, or L-ATH. Vasculature of cultured explants was
      quantified by X-galactosidase staining. RNA was analyzed with murine gene probes
      for angiopoietin (Ang)-1, Ang-2, fibroblast growth factor 2 (FGF2), platelet
      endothelial cell adhesion molecule (PECAM), and vascular endothelial growth
      factor (VEGF). FGF2-supplemented medium was used to test contribution to effects
      of L-AT and L-ATH on angiogenesis. Epithelial branching morphogenesis was
      inhibited by L-AT (P = 0.003) and heparin (P < 0.001). L-AT and heparin decreased
      relative vascular area compared with PBS, ATH, and L-ATH. Expressions of all
      genes studied were downregulated by L-AT. However, L-AT and L-ATH inhibited
      branching morphogenesis and vasculature with added FGF2. These findings indicate
      that covalent linkage of AT to heparin negates disruptive effects of these
      moieties on lung morphology, vascularization, and growth factor gene expression.
      ATH may have enhanced safety as an anticoagulant during vascular development.

PMID- 19112104
TI  - Secreted cyclophilin A, a peptidylprolyl cis-trans isomerase, mediates matrix
      assembly of hensin, a protein implicated in epithelial differentiation.
AB  - Hensin is a rabbit ortholog of DMBT1, a multifunctional, multidomain protein
      implicated in the regulation of epithelial differentiation, innate immunity, and
      tumorigenesis. Hensin in the extracellular matrix (ECM) induced morphological
      changes characteristic of terminal differentiation in a clonal cell line (clone
      C) of rabbit kidney intercalated cells. Although hensin is secreted in monomeric
      and various oligomeric forms, only the polymerized ECM form is able to induce
      these phenotypic changes. Here we report that hensin secretion and matrix
      assembly were inhibited by the peptidylprolyl cis-trans isomerase (PPIase)
      inhibitors cyclosporin A (CsA) and a derivative of cyclosporin A with
      modifications in the d-Ser side chain (Cs9) but not by the calcineurin pathway
      inhibitor FK506. PPIase inhibition led to failure of hensin polymerization in the
      medium and ECM, plus the loss of apical cytoskeleton, apical microvilli, and the
      columnar epithelial shape of clone C cells. Cyclophilin A was produced and
      secreted into the media to a much greater extent than cyclophilins B and C. Our
      results also identified the direct CsA-sensitive interaction of cyclophilin A
      with hensin, suggesting that cyclophilin A is the PPIase that mediates the
      polymerization and matrix assembly of hensin. These results are significant
      because this is the first time a direct role of peptidylprolyl cis-trans
      isomerase activity has been implicated in the process of epithelial
      differentiation.

PMID- 19112105
TI  - Caspase-8 mediates mitochondrial release of pro-apoptotic proteins in a manner
      independent of its proteolytic activity in apoptosis induced by the protein
      synthesis inhibitor acetoxycycloheximide in human leukemia Jurkat cells.
AB  - The cysteine protease caspase-8 plays an essential role in apoptosis induced by
      death receptors. The protein synthesis inhibitor acetoxycycloheximide (Ac-CHX)
      has been previously shown to induce rapid apoptosis mediated by the release of
      cytochrome c in human leukemia Jurkat cells. In this study, the novel molecular
      mechanism that links caspase-8 to the mitochondrial release of pro-apoptotic
      proteins has been identified. Jurkat cells deficient in caspase-8 were more
      resistant to Ac-CHX than wild-type Jurkat cells and manifested decreased
      apoptosis induction and caspase activation as well as inefficient release of
      cytochrome c, Smac/DIABLO, and AIF into the cytosol. In contrast to Fas ligand
      stimulation, the general caspase inhibitor barely prevented the mitochondrial
      release of these pro-apoptotic proteins in Ac-CHX-treated cells, suggesting that
      caspase-8 activity is dispensable for triggering the mitochondrial pathway in Ac
      CHX-induced apoptosis. Consistent with this notion, caspase-8-deficient Jurkat
      cells reconstituted with catalytically inactive caspase-8 became sensitive to Ac
      CHX and exhibited apoptosis, caspase activation, the liberation of pro-apoptotic
      proteins into the cytosol, and Bak conformational change as efficiently as wild
      type Jurkat cells. Unlike caspase-3, -6, -7, and -9, a small but significant
      portion of caspase-8 was found to localize in mitochondria before and after
      exposure to Ac-CHX. These results clearly demonstrate that caspase-8 is able to
      mediate the mitochondrial release of pro-apoptotic proteins in a manner
      independent of its proteolytic activity in Ac-CHX-induced apoptosis.

PMID- 19112106
TI  - Functional characterization of the Bombyx mori fatty acid transport protein
      (BmFATP) within the silkmoth pheromone gland.
AB  - Fatty acid transport protein (FATP) is an evolutionarily conserved membrane-bound
      protein that facilitates the uptake of extracellular long chain fatty acids. In
      humans and mice, six FATP isoforms have been identified and their tissue-specific
      distributions suggest that each plays a discrete role in lipid metabolism in
      association with fatty acid uptake. While the presence of FATP homologs in
      insects has been demonstrated, their functional role remains to be characterized.
      Pheromonogenesis is defined as the dynamic period in which all machinery required
      for sex pheromone biosynthesis is generated and organized within the pheromone
      gland (PG) cells. By exploiting this unique system in the PG of the silkmoth,
      Bombyx mori, we found that BmFATP is predominantly expressed in the PG and
      undergoes up-regulation 1 day prior to eclosion. Before eclosion, B. mori PG
      cells accumulate cytoplasmic lipid droplets (LDs), which play a role in storing
      the pheromone (bombykol) precursor fatty acid in the form of triacylglycerol.
      RNAi-mediated gene silencing of BmFATP in vivo significantly suppressed LD
      accumulation by preventing the synthesis of triacylglycerols and resulted in a
      significant reduction in bombykol production. These results, in conjunction with
      the findings that BmFATP stimulates the uptake of extracellular long-chain fatty
      acids and BmFATP knockdown reduces cellular long-chain acyl-CoA synthetase
      activity, suggest that BmFATP plays an essential role in bombykol biosynthesis by
      stimulating both LD accumulation and triacylglycerol synthesis via a process
      called vectorial acylation that couples the uptake of extracellular fatty acids
      with activation to CoA thioesters during pheromonogenesis.

PMID- 19112107
TI  - CXCL8/IL8 stimulates vascular endothelial growth factor (VEGF) expression and the
      autocrine activation of VEGFR2 in endothelial cells by activating NFkappaB
      through the CBM (Carma3/Bcl10/Malt1) complex.
AB  - Vascular endothelial growth factor (VEGF) is a potent mitogen and permeability
      factor for endothelial cells that plays a central role in angiogenesis, vascular
      maintenance, inflammation, and cancer. VEGF also mediates the homeostatic
      adaptation to hypoxic conditions by promoting an increase in vascular density to
      compensate for decreased oxygenation. This process is triggered by an oxygen
      sensitive transcription factor, hypoxia-inducible factor-1 (HIF1alpha), which
      becomes active in hypoxic tissues, leading to the synthesis and secretion of
      VEGF. The role of HIF1alpha in other processes that involve angiogenesis such as
      in inflammation is less clear. Of interest, endothelial cells not only respond to
      but also store and secrete VEGF, which is required for the maintenance of the
      integrity of the vascular system. How this intracellular pool of VEGF is
      regulated is still not understood. Here, we found that CXCL8/IL8, a potent
      proangiogenic and inflammatory chemokine, up-regulates VEGF mRNA and protein
      levels in endothelial cells by acting on its cognate receptor, CXCR2, and that
      this results in the autocrine activation of VEGFR2. Surprisingly, this process
      does not involve HIF1alpha but instead requires the activation of the
      transcription factor NFkappaB. Furthermore, we identified the components of the
      CBM complex, Carma3, Bcl10, and Malt1, as key mediators of the CXCL8/IL8-induced
      NFkappaB activation and VEGF up-regulation. Together, these findings support the
      existence of an NFkappaB-mediated pathway by which the proinflammatory chemokine
      CXCL8/IL8 controls the expression of VEGF in endothelial cells, thereby promoting
      the activation of VEGF receptors in an autocrine fashion.

PMID- 19112109
TI  - Review paper: Human tissues for discovery biomarker pharmaceutical research: the
      experience of the Indiana University Simon Cancer Center-Lilly Research Labs
      Tissue/Fluid BioBank.

PMID- 19112110
TI  - Review paper: Current strategies in the development of anti-obesity drugs and
      their safety concerns.
AB  - Obesity is a well-established risk factor for hypertension, hyperlipidemia, type
      II diabetes, coronary heart disease, stroke, obstructive sleep apnea, asthma,
      orthopedic disorders, and certain cancers. Despite this risk, the prevalence of
      obesity continues to increase worldwide, and there is a growing demand for safe
      and effective antiobesity drugs. Previous antiobesity drugs or anorexigens,
      particularly centrally acting agents, have poor safety records. Life-threatening
      safety issues led to the withdrawal of aminorex in 1968, fenfluramine and
      dexfenfluramine in 1997, and phenylpropanolamine in 2000. Many of the safety
      issues, such as valvulopathy with fenfluramine and pulmonary arterial
      hypertension with aminorex, were initially not predicted by routine preclinical
      toxicology studies. To date, there are no validated animal models or preclinical
      and/or toxicologic screens to accurately predict anorexigen-induced valvulopathy
      and pulmonary arterial hypertension in humans. This review covers the current
      state of antiobesity drugs and their safety concerns, and highlights new
      therapeutic targets and scientific advances toward the development of appropriate
      animal models by using novel techniques that will aid in understanding
      pathogenesis and pathophysiology of anorexigen-related safety issues.

PMID- 19112111
TI  - Clinical, histologic, and immunohistochemical analyses of feline squamous cell
      carcinoma in situ.
AB  - Actinic keratosis (AK) and Bowenoid in situ carcinoma (BISC) are two distinct
      forms of in situ squamous cell carcinoma in felines. They usually occur on
      different locations and present with specific clinical and histologic features.
      However, in some cases, these diseases cannot be distinguished either clinically
      or histopathologically. The aim of the present study was to determine the
      accuracy of diagnosis based on clinical or histologic criteria alone, and whether
      immunohistochemistry for papillomavirus or p53 can improve the accuracy of
      diagnosis. A series of in situ squamous cell carcinoma cases (n = 45) were
      selected according to their location and initial histologic classification and
      subsequently classified as AK (n = 22) or BISC (n = 23) according to the clinical
      criteria and were reevaluated histologically by 2 dermatopathologists. All BISC
      cases and most of the AK cases (n = 15) were confirmed histologically. In 7 cases
      clinically classified as AK, this diagnosis was not unanimously confirmed
      histologically because of the presence of overlapping features. P53
      immunoreactivity was observed in 11/14 (79%) confirmed AK cases and in 4/22 (18%)
      BISC cases, while papillomavirus antigen was not detected in any confirmed AK
      case but was detected in 11/23 (48%) BISC cases. It was concluded that BISC can
      usually be reliably diagnosed histologically. The histologic diagnosis of lesions
      clinically suggestive of AK might sometimes be difficult. Results of
      immunohistochemistry for p53 and papillomavirus antigen were supportive for a
      role of sun exposure and papillomavirus in the pathogenesis of AK and BISC,
      respectively.

PMID- 19112112
TI  - Detection of canine oral papillomavirus DNA in conjunctival epithelial
      hyperplastic lesions of three dogs.
AB  - Papillomavirus infections are responsible for plaques and papillomas in various
      locations on the skin and in mucous membranes. The aim of this report was to
      describe morphologic features of a viral pigmented conjunctival plaque and 2
      conjunctival squamous papillomas in 3 dogs, and to investigate these lesions for
      the presence of papillomavirus DNA by polymerase chain reaction (PCR), DNA
      sequence analysis, and in situ hydridization (ISH). Histopathology revealed in
      all neoplasms various degrees of epithelial hyperplasia, acanthosis, and
      hyperkeratosis with koilocytosis. In all lesions E6, E7, and L1 gene fragments of
      canine oral papillomavirus (COPV) DNA were detected by PCR and sequencing
      analysis. ISH revealed COPV DNA in a highly specific pattern within nuclei of the
      hyperplastic epithelium. The presence of canine papillomavirus in ocular
      conjunctival plaques and papillomas suggests these benign lesions may have the
      potential for malignant transformation. This is the first time that the
      lambdapapillomavirus COPV has been detected in ocular epithelial hyperplastic
      lesions.

PMID- 19112113
TI  - Serial passage of sheep scrapie inoculum in Suffolk sheep.
AB  - Scrapie is a naturally occurring fatal neurodegenerative disease of sheep and
      goats. Susceptibility to the disease is partly dependent upon the genetic makeup
      of the host. In a recent study, it was shown that sheep intracerebrally
      inoculated with a US scrapie agent (No. 13-7) developed scrapie and survived for
      an average of 19 months post inoculation. In the present study, when this scrapie
      inoculum was further passaged for 3 successive generations, the survival time was
      reduced by approximately 8 months in scrapie-susceptible (QQ on prion protein
      gene [PRNP] at codon 171) Suffolk sheep. It is concluded that inoculum No. 13-7
      appears to have been stabilized in susceptible (171 QQ) Suffolk sheep and may be
      considered a specific isolate of sheep scrapie agent in the USA and therefore
      that it can be used to evaluate other isolates of sheep scrapie in this country.

PMID- 19112114
TI  - Bovine viral diarrhea virus abortion in goats housed with persistently infected
      cattle.
AB  - Twenty-four border disease virus-seronegative, pregnant, mixed breed goats were
      experimentally comingled with 3 heifers persistently infected with bovine viral
      diarrhea virus type 2a (BVDV-2a). Twelve of the 24 exposed does aborted. Twenty
      nine fetuses and 16 placentas from affected does were submitted to the Oklahoma
      Animal Disease Diagnostic Laboratory for a necropsy examination. Infection with
      BVDV was confirmed with a combination of immunohistochemistry, BVDV-2 polymerase
      chain reaction, and virus isolation in 19 of the 29 fetuses. On gross examination
      of the 19 fetuses and placentas in which BVDV-2a infection was confirmed, a mild
      placentitis (3/19), fetal mummification (1/19), and facial deformities (4/19)
      were noted. Histologically, placentitis (2/19), myocarditis (4/19), thymic
      depletion (5/19), choroid plexitis (3/19), encephalitis (2/19), and cerebral
      gliosis (1/19) were noted. Other causes of abortion in goats, including common
      bacterial and viral infections, were ruled out with histology, virus isolation,
      polymerase chain reaction, and aerobic bacteriologic cultures. As supported by
      the findings in this case, BVDV-2a should be included as a differential for
      abortion in goats. This is the first report of abortion in goats after exposure
      to persistently infected cattle.

PMID- 19112115
TI  - Distribution of bovine viral diarrhea virus antigen in aborted fetal and neonatal
      goats by immunohistochemistry.
AB  - Bovine viral diarrhea virus (BVDV) infection in goats can result in severe
      reproductive losses, with abortion rates reaching 80%. Infection with BVDV in
      aborted goat fetuses and stillborn kids can result in placentitis, encephalitis,
      myocarditis, and thymic depletion. This study investigates the distribution of
      viral antigen within the organ systems of aborted goat fetuses, stillborn kids,
      and nonviable kids infected with BVDV at various stages of gestation using
      immunohistochemistry (IHC). Virus antigen was detected within the placenta
      (8/13), thymus (4/9), heart (4/11), and brain (4/15) of affected goats.
      Uncommonly, BVDV antigen was detected within the skin (1/14), liver (1/13),
      kidney (1/12), lung (1/11), and trachea (1/3). BVDV antigen was not detected
      within the spleen (0/9), nasal turbinate (0/2), or thyroid (0/3). The results of
      this study indicate that placenta, heart, thymus, and brain are the most reliable
      tissues for BVDV antigen detection using IHC in aborted goat fetuses.

PMID- 19112116
TI  - Detection of pathologic prion protein in the olfactory bulb of natural and
      experimental bovine spongiform encephalopathy affected cattle in Great Britain.
AB  - To investigate the relative involvement of the olfactory region in classical
      bovine spongiform encephalopathy (BSE), immunohistochemical labeling of prion
      protein scrapie (PrP(Sc)) was scored in the brainstem, frontal cerebral cortex,
      and olfactory bulb of cattle with natural and experimental clinical cases of BSE
      in Great Britain. The intensity of immunolabeling was greatest in the brainstem,
      but PrP(Sc) was also detected in the olfactory bulb and the cerebral cortex. A
      diffuse, nonparticulate labeling, possibly due to abundance of cellular PrP, was
      consistently observed in the olfactory glomeruli of the cases and negative
      controls. Involvement of the olfactory bulb in BSE and other naturally occurring
      TSEs of animals raises speculation as to an olfactory portal of infection or a
      route of excretion of the prion agent.

PMID- 19112117
TI  - Feline gastrointestinal eosinophilic sclerosing fibroplasia.
AB  - A retrospective study of cases of a unique intramural inflammatory mass within
      the feline gastrointestinal tract was performed in order to describe and
      characterize the lesion. Twenty-five cases were identified from archival surgical
      and postmortem tissues. The lesion most often occurred as an ulcerated intramural
      mass at the pyloric sphincter (n = 12) or the ileocecocolic junction or colon (n
      = 9); the remaining cases were in the small intestine. Seven cases also had lymph
      node involvement. The lesions were characterized by eosinophilic inflammation,
      large reactive fibroblasts, and trabeculae of dense collagen. Intralesional
      bacteria were identified in 56% of the cases overall and all of the ileocecocolic
      junction and colon lesions. Fifty-eight percent of cats tested had peripheral
      eosinophilia. Cats treated with prednisone had a significantly longer survival
      time than those receiving other treatments. We propose that this is a unique
      fibroblastic response of the feline gastrointestinal tract to eosinophilic
      inflammation that in some cases is associated with bacteria. The lesion is often
      grossly and sometimes histologically mistaken for neoplasia.

PMID- 19112118
TI  - Septicemia in a neonatal calf associated with Chromobacterium violaceum.
AB  - Chromobacterium violaceum infections are highly fatal and rarely reported in
      domestic animals. This report describes a fatal case of C. violaceum septicemia
      in a 7-day-old female beef calf. The calf had necrosuppurative omphalophlebitis,
      necrotizing interstitial pneumonia, necrosuppurative hepatitis and splenitis,
      anterior uveitis with hypopyon, suppurative polyarthritis, and disseminated
      hemorrhagic meningitis with multifocal necrotizing encephalitis. Histologically,
      clusters of gram-negative bacilli were found in many of the lesions. C. violaceum
      was isolated in high numbers from the lungs, liver, spleen, carpus, and in pure
      culture from the cerebrospinal fluid. To our knowledge, this is the first case
      report of chromobacteriosis in a calf.

PMID- 19112119
TI  - Hypoxic/ischemic encephalopathy associated with placental insufficiency in a
      cloned foal.
AB  - Hypoxic/ischemic encephalopathy in a cloned American Quarter horse foal was
      initially associated with placental insufficiency and exacerbated by protracted
      hypotension during anesthesia for a surgical procedure. The foal, born at the
      Texas A&M Veterinary Medical Center, was diagnosed at birth with neonatal
      maladjustment syndrome that was accompanied by dysmaturity, muscle contracture of
      the front limbs, and a blood clot within the lumen of the urinary bladder.
      Seizures that developed after anesthesia were attributed to hypoxia/ischemia
      during anesthesia and culminated in death. Macroscopically, the cerebrum had
      flattened cerebral gyri with shallow sulci, yellowish cortical discoloration, and
      apple-green autofluorescence (under 365-nm ultraviolet light) at the
      cortical/white matter junction. Microscopically, there was laminar cortical
      necrosis with prominent diffuse ischemic change of neuronal cell bodies. The
      white matter had prominent rarefaction with focal axonal and myelin degeneration
      and focal macrophage (gitter cell) accumulation. Additionally, there was
      astrocytic hypertrophy with gemistocyte formation. The chorioallantois was
      diffusely thickened in the area corresponding to the uterine horns.
      Histologically, microcotyledons were markedly attenuated with absence of
      chorionic villi.

PMID- 19112120
TI  - Disseminated melanoma in a dog with involvement of leptomeninges and bone marrow.
AB  - An 11-year-old, Black and Tan Coonhound dog was presented with a history of
      lameness of the right hind leg for 2 months, osteolysis in the right distal
      femur, a pulmonary mass, and a presumptive diagnosis of osteosarcoma. By
      cytologic examination, neoplastic melanocytes were noted from fine needle
      aspirates of the femoral and pulmonary masses. Postmortem examination revealed a
      disseminated melanoma involving the right femoral bone marrow, lung, multiple
      lymph nodes, and adrenal gland, with diffuse infiltration of the leptomeninges of
      the brain and spinal cord. This case report describes a unique presentation of
      canine melanoma, which in some ways resembles leptomeningeal melanomatosis, a
      rare human melanoma variant.

PMID- 19112121
TI  - Ductal plate malformation in a nonhuman primate.
AB  - During necropsy of a 6-year-old, male African Green monkey (Cercopithecus
      aethiops), multifocal pale, white to tan areas, 1-2 cm in diameter, were noted in
      the right lateral lobe, medial lobe, and capsular surface of the liver. Light
      microscopic examination of the liver revealed numerous spindle cells dispersed
      within interconnecting, broad bands of collagen, up to 200 microm in width, which
      often spanned and connected portal areas. A diagnosis of hepatic ductal plate
      malformation, most closely resembling congenital hepatic fibrosis with von
      Meyenburg complexes, was made. Few cases of ductal plate malformations in
      domestic animals are reported in the literature. To our knowledge, this is the
      first case reported in a nonhuman primate.

PMID- 19112122
TI  - Selective vulnerability of peripheral nerves in avian riboflavin deficiency
      demyelinating polyneuropathy.
AB  - Riboflavin (vitamin B2) deficiency in young chickens produces a demyelinating
      peripheral neuropathy. In this study, day-old broiler meat chickens were fed a
      riboflavin-deficient diet (1.8 mg/kg) and killed on posthatch days 6, 11, 16, 21,
      and 31, while control chickens were given a conventional diet containing 5.0
      mg/kg riboflavin. Pathologic changes were found in sciatic, cervical, and lumbar
      spinal nerves of riboflavin-deficient chickens from day 11 onwards, characterized
      by endoneurial oedema, hypertrophic Schwann cells, tomacula (redundant myelin
      swellings), demyelination/remyelination, lipid deposition, and fibroblastic onion
      bulb formation. Similar changes were also found in large and medium intramuscular
      nerves, although they were less severe in the latter. However, by contrast,
      ventral and dorsal spinal nerve roots, distal intramuscular nerves, and
      subcutaneous nerves were normal at all time points examined. These findings
      demonstrate, for the first time, that riboflavin deficiency in young, rapidly
      growing chickens produces selective injury to peripheral nerve trunks, with
      relative sparing of spinal nerve roots and distal nerve branches to muscle and
      skin. These novel findings suggest that the response of Schwann cells in
      peripheral nerves with riboflavin deficiency differs because either there are
      subsets of these cells in, or there is variability in access of nutrients to,
      different sites within the nerves.

PMID- 19112123
TI  - Clinico-pathologic features of fatal disease attributed to new variants of
      endotheliotropic herpesviruses in two Asian elephants (Elephas maximus).
AB  - The first herpesviruses described in association with serious elephant disease
      were referred to as endotheliotropic herpesviruses (EEHV) because of their
      ability to infect capillary endothelial cells and cause potentially fatal
      disease. Two related viruses, EEHV1 and EEHV2, have been described based on
      genetic composition. This report describes the similarities and differences in
      clinicopathologic features of 2 cases of fatal endotheliotropic herpesvirus
      infections in Asian elephants caused by a previously unrecognized virus within
      the betaherpesvirus subfamily. EEHV3 is markedly divergent from the 2 previously
      studied fatal probosciviruses, based on polymerase chain reaction sequence
      analysis of 2 segments of the viral genome. In addition to ascites, widespread
      visceral edema, petechiae, and capillary damage previously reported, important
      findings with EEHV3 infection were the presence of grossly visible renal
      medullary hemorrhage, a tropism for larger veins and arteries in various tissues,
      relatively high density of renal herpetic inclusions, and involvement of the
      retinal vessels. These findings indicate a less selective organ tropism, and this
      may confer a higher degree of virulence for EEHV3.

PMID- 19112124
TI  - Characterization of a degenerative cardiomyopathy associated with domoic acid
      toxicity in California sea lions (Zalophus californianus).
AB  - Domoic acid, produced by marine algae, can cause acute and chronic neurologic
      sequela in California sea lions (Zalophus californianus) from acute toxicity or
      sublethal exposure. Eight sea lions, representing acute and chronic cases, both
      sexes, and all age classes, were selected to demonstrate a concurrent
      degenerative cardiomyopathy. Critical aspects of characterizing the
      cardiomyopathy by lesion distribution and morphology were the development of a
      heart dissection and tissue-trimming protocol and the delineation of the cardiac
      conducting system by histomorphology and immunohistochemistry for neuron-specific
      protein gene product 9.5. Histopathologic features and progression of the
      cardiomyopathy are described, varying from acute to chronic active and mild to
      severe. The cardiomyopathy is distinguished from other heart lesions in
      pinnipeds. Based on histopathologic features, immunopositive staining for cleaved
      caspase-3, and comparison with known, similar-appearing cardiomyopathies, the
      proposed pathogenesis for the degenerative cardiomyopathy is the primary or at
      least initial direct interaction of domoic acid with receptors that are suspected
      to exist in the heart. l-Carnitine, measured in the heart and skeletal muscle,
      and troponin-I, measured in serum collected at the time of death from additional
      animals (n = 58), were not predictive of the domoic acid-associated
      cardiomyopathy. This degenerative cardiomyopathy in California sea lions
      represents another syndrome beyond central neurologic disease associated with
      exposure to domoic acid and may contribute to morbidity and mortality.

PMID- 19112125
TI  - Bilateral nocardial endophthalmitis in a prothonotary warbler (Protonotaria
      citrea).
AB  - A 7-year-old captive female prothonotary warbler (Protonotaria citrea) died
      following chronic feather and weight loss. At necropsy, the right eye had a 2 x 2
      x 1 mm corneal plaque of inspissated yellow-tan material and edema of the lower
      eyelid. Microscopically, both eyes exhibited diffuse, severe pyogranulomatous
      endophthalmitis with retinal necrosis and detachment. Numerous intralesional
      branching, gram-positive, beaded, filamentous bacteria formed a thick mat
      attached to the retinal pigmented epithelium and extending into the pecten.
      Bacteria were strongly acid-fast positive by Fite's stain but only occasionally
      acid-fast positive by Ziehl-Neelsen staining, a characteristic consistent with a
      Nocardia spp. Infected regions demonstrated positive in situ hybridization
      reactivity with a probe complementary to the 16S rRNA gene of Nocardia spp. There
      was no evidence of primary bacterial infection in the other organs examined.

PMID- 19112126
TI  - Mice overexpressing murine oncostatin M (OSM) exhibit changes in hematopoietic
      and other organs that are distinct from those of mice overexpressing human OSM or
      bovine OSM.
AB  - Oncostatin M (OSM) and leukemia inhibitory factor (LIF) belong to the interleukin
      6 family of cytokines. The authors' previous in vitro work demonstrated that in
      mouse cells mouse OSM (mOSM) signals through a heterodimeric receptor complex
      incorporating the mOSM-specific receptor mOSMRbeta while human OSM (hOSM) and
      bovine OSM (bOSM) use the mouse LIF receptor mLIFRbeta rather than mOSMRbeta.
      These in vitro data suggest that prior studies in mouse systems with hOSM or bOSM
      (the usual molecules used in early studies) reflect LIF rather than OSM biology.
      The current work assessed whether or not this divergence in actions among these
      three OSMs also occurs in vivo in mouse models. Adult female (C57BL/6J x DBA/2J)
      F(1) mice were engineered to stably overexpress mOSM, hOSM, or bOSM by retrovirus
      mediated gene transfer (n = 10 or more per group). After 4 weeks, molecular and
      hematologic profiles and anatomic phenotypes in multiple organs were assessed by
      standard techniques. Animals overexpressing either hOSM or bOSM had an identical
      phenotype resembling that associated with LIF activation, including significant
      hematologic abnormalities (anemia, neutrophilia, lymphopenia, eosinopenia, and
      thrombocytosis); weight loss; profound enlargement (lymph node, spleen) and/or
      structural reorganization (lymph node, spleen, thymus) of lymphoid organs; and
      severe osteosclerosis. In contrast, mice overexpressing mOSM did not develop
      hematologic changes, weight loss, or osteosclerosis and exhibited more modest and
      anatomically distinct restructuring of lymphoid organs. These data indicate that
      activities imputed to OSM and the mOSMRbeta signaling pathway using in vitro and
      in vivo mouse experimental systems are unique to mOSM.

PMID- 19112127
TI  - Bronchointerstitial pneumonia in guinea pigs following inoculation with H5N1 high
      pathogenicity avian influenza virus.
AB  - The H5N1 high-pathogenicity avian influenza (HPAI) viruses have caused widespread
      disease of poultry in Asia, Africa and the Middle East, and sporadic human
      infections. The guinea pig model has been used to study human H3N2 and H1N1
      influenza viruses, but knowledge is lacking on H5N1 HPAI virus infections. Guinea
      pigs were inoculated intranasally or intragastrically with A/Vietnam/1203/04
      (VN/04) or A/Muscovy duck/Vietnam/209/05 (MDk/VN/05) viruses. Mild listlessness
      was seen at 2 and 3 days postinoculation (DPI) in guinea pigs inoculated
      intranasally with VN/04 virus. At 5 DPI, the guinea pigs had bronchointerstitial
      pneumonia and virus was identified in bronchiolar epithelium and alveolar
      macrophages. Virus was isolated from the lungs but was lacking from other organs.
      Minimal lung lesions were seen in intranasal MDk/VN/06 group and virus was not
      detected, but serologic evidence of infection was observed. Intragastric exposure
      failed to produce infection or lesions with either virus. The localized
      respiratory disease in guinea pigs with H5N1 viruses was very similar to that of
      H3N2 and H1N1 influenza in humans and was less severe than reported for H5N1
      human cases.

PMID- 19112128
TI  - Effects of neonatally administered high-dose diethylstilbestrol on the induction
      of mammary tumors induced by 7,12-dimethylbenz[a]anthracene in female rats.
AB  - The aim of this study was to investigate the effects of neonatal administration
      of a relatively high dose of diethylstilbestrol (DES) on the induction of mammary
      carcinomas (MCs) and benign proliferative lesions (PLs) induced by 7,12
      dimethylbenz[a]anthracene (DMBA) in female rats. Three different terms of daily
      administration of DES (10 microg) were used: 0-14, 0-5, and 6-14 days after
      birth. Control animals were administered solvent (oil) alone once daily from 0 to
      14 days after birth. Rats were given DMBA (10 mg) at 50 days after birth. All
      rats administered DES showed persistent estrus and anovulatory ovaries. In rats
      administered DES from 0 to 14 and 0 to 5 days after birth there was protection
      from development of MCs and PLs, and serum levels of both estrogen and
      progesterone were significantly lower than in the control animals at 100 days
      after birth. In rats administered DES from 6 to 14 days after birth, the
      incidence of MCs was equal to that of the control animals (100%), and the number
      of PLs was significantly higher than in the control animals. The critical period
      for exposure to endocrine disruptors, such as DES, affecting the induction of MCs
      and PLs may be from 0 to 5 days after birth.

PMID- 19112129
TI  - Diagnostic exercise: Tyzzer's disease, distemper, and coccidiosis in a pup.
AB  - A 2-month-old mongrel dog had multifocal necrotizing hepatitis, interstitial
      pneumonia, and hemorrhagic enteritis. Immunohistochemistry detected antigens of
      Clostridium piliforme in the intestine and liver, and antigens of canine
      distemper virus within the lung, urinary bladder, brain, spleen, and liver.
      Furthermore, uncharacterized intralesional coccidian protozoa were observed
      within the intestine.

PMID- 19112131
TI  - Xanthogranulomatous inflammation.

PMID- 19112133
TI  - Ultrastructure and physical properties of an adhesive surface, the toe pad
      epithelium of the tree frog, Litoria caerulea White.
AB  - Knowledge of both surface structure and physical properties such as stiffness and
      elasticity are essential to understanding any adhesive system. In this study of
      an adhesion surface in the tree frog, Litoria caerulea White, a variety of
      techniques including atomic force microscopy were used to investigate the
      microstructure and properties of an epithelium that adheres through wet adhesion.
      Litoria toe pads consist of a hexagonal array of flat-topped epithelial cells,
      separated by mucus-filled channels. Under an atomic force microscope, this ;flat'
      surface is highly structured at the nanoscale, consisting of a tightly packed
      array of columnar nanopillars (described as hemidesmosomes by previous authors),
      326+/-84 nm in diameter, each of which possesses a central dimple 8+/-4 nm in
      depth. In fixed tissue (transmission electron microscopy), the nanopillars are
      approximately as tall as they are broad. At the gross anatomical level, larger
      toe pads may be subdivided into medial and lateral parts by two large grooves.
      Although the whole toe pad is soft and easily deformable, the epithelium itself
      has an effective elastic modulus equivalent to silicon rubber (mean E(eff)=14.4+/
      20.9 MPa; median E(eff)=5.7 MPa), as measured by the atomic force microscope in
      nanoindentation mode. The functions of these structures are discussed in terms of
      maximising adhesive and frictional forces by conforming closely to surface
      irregularities at different length scales and maintaining an extremely thin fluid
      layer between pad and substrate. The biomimetic implications of these findings
      are reviewed.

PMID- 19112134
TI  - Effects of cocaine on honey bee dance behaviour.
AB  - The role of cocaine as an addictive drug of abuse in human society is hard to
      reconcile with its ecological role as a natural insecticide and plant-protective
      compound, preventing herbivory of coca plants (Erythroxylum spp.). This paradox
      is often explained by proposing a fundamental difference in mammalian and
      invertebrate responses to cocaine, but here we show effects of cocaine on honey
      bees (Apis mellifera L.) that parallel human responses. Forager honey bees
      perform symbolic dances to advertise the location and value of floral resources
      to their nest mates. Treatment with a low dose of cocaine increased the
      likelihood and rate of bees dancing after foraging but did not otherwise increase
      locomotor activity. This is consistent with cocaine causing forager bees to
      overestimate the value of the floral resources they collected. Further, cessation
      of chronic cocaine treatment caused a withdrawal-like response. These
      similarities likely occur because in both insects and mammals the biogenic amine
      neuromodulator systems disrupted by cocaine perform similar roles as modulators
      of reward and motor systems. Given these analogous responses to cocaine in
      insects and mammals, we propose an alternative solution to the paradox of cocaine
      reinforcement. Ecologically, cocaine is an effective plant defence compound via
      disruption of herbivore motor control but, because the neurochemical systems
      targeted by cocaine also modulate reward processing, the reinforcing properties
      of cocaine occur as a ;side effect'.

PMID- 19112135
TI  - Temperature adaptation of cytosolic malate dehydrogenases of limpets (genus
      Lottia): differences in stability and function due to minor changes in sequence
      correlate with biogeographic and vertical distributions.
AB  - We characterized functional and structural properties of cytoplasmic malate
      dehydrogenases (cMDHs) from six limpets of the genus Lottia that have different
      vertical and latitudinal distributions. Particular attention was given to the
      cryptic species pair Lottia digitalis (northern occurring) and L. austrodigitalis
      (southern occurring) because of recent contraction in the southern range of L.
      digitalis and a northward range extension of L. austrodigitalis. As an index of
      adaptation of function, we measured the effects of temperature on the apparent
      Michaelis-Menten constant (K(m)) of the cofactor NADH (K(m)(NADH)). K(m)(NADH)
      values of cMDHs from the mid- to high-intertidal, low-latitude species L. scabra
      and L. gigantea were less sensitive to high temperature than those of cMDHs from
      the low- and mid-intertidal, high-latitude species L. scutum and L. pelta. cMDH
      of L. digitalis was more sensitive to high temperatures than the cMDH ortholog of
      L. austrodigitalis. Thermal stability (rate of loss of activity at 42.5 degrees
      C) showed a similar pattern of interspecific variation. Comparison of the deduced
      amino acid sequences showed that interspecific differences ranged from one to as
      many as 17 residues. Differences in K(m)(NADH) and thermal stability between
      orthologs of L. digitalis and L. austrodigitalis result from a single amino acid
      substitution. At position 291, the glycine residue in cMDH of L. digitalis is
      replaced by a serine in cMDH of L. austrodigitalis, a change that favors
      additional hydrogen bonding and reduced conformational entropy. This difference
      between closely related congeners demonstrates the role of minor alterations in
      protein sequence in temperature adaptation and suggests that such variation is
      important in governing shifts in biogeographic range in response to climate
      change.

PMID- 19112136
TI  - The influence of experience in orientation: GPS tracking of homing pigeons
      released over the sea after directional training.
AB  - Flight experience is one of the factors that influences initial orientation of
      displaced homing pigeons (Columba livia). Prior studies showed a systematic
      dependence of initial orientation on previously flown direction. Using GPS data
      loggers, this study sought to examine the effect of previous directional training
      of 40 homing pigeons when they were released over the sea, in the absence of
      proximal landmarks, in a direction almost perpendicular to that of previous
      training flights. Our results demonstrated that previous directional training
      evoked a systematic and predicted deviation from the beeline over the sea that
      appeared as a compromise between the direction of training and the direction to
      the loft. Pigeons were able to efficiently correct their flight direction only
      once over land, where they flew significantly slower and less directly than over
      the sea.

PMID- 19112137
TI  - Regional variation in parvalbumin isoform expression correlates with muscle
      performance in common carp (Cyprinus carpio).
AB  - The mechanical properties of the axial muscles vary along the length of a fish's
      body. This variation in performance correlates with the expression of certain
      muscle proteins. Parvalbumin (PARV) is an important calcium binding protein that
      helps modulate intracellular calcium levels which set the size and shape of the
      muscle calcium transient. It therefore has a central role in determining the
      functional properties of the muscle. Transcript data revealed eight specific
      isoforms of PARV in common carp (Cyprinus carpio) skeletal muscle which we
      classified as alpha1 and beta1-7. This study is the first to show expression of
      all eight skeletal muscle PARV isoforms in carp at the protein level and relate
      regional differences in expression to performance. All of the PARV isoforms were
      characterised at the protein level using 2D-PAGE and tandem mass spectrometry.
      Comparison of carp muscle from different regions of the fish revealed a higher
      level of expression of PARV isoforms beta4 and beta5 in the anterior region,
      which was accompanied by an increase in the rate of relaxation. We postulate that
      changes in specific PARV isoform expression are an important part of the adaptive
      change in muscle mechanical properties in response to varying functional demands
      and environmental change.

PMID- 19112138
TI  - Straight walking and turning on a slippery surface.
AB  - In stick insects, walking is the result of the co-action of different pattern
      generators for the single legs and coordinating inter-leg influences. We have
      used a slippery surface setup to understand the role the local neuronal
      processing in the thoracic ganglia plays in the ability of the animal to show
      turning movements. To achieve this, we removed the influence of mechanical
      coupling through the ground by using the slippery surface and removed sensory
      input by the successive amputation of neighboring legs. We analyzed the walking
      pattern of the front, middle and hind legs of tethered animals mounted above the
      surface and compared the kinematics of the straight walking legs with those of
      the curve walking inside and outside legs. The walking pattern was monitored both
      electrically through tarsal contact measurement and optically by using
      synchronized high-speed video. The vectors of leg movement are presented for the
      intact and a reduced preparation. Animals showed the ability to walk in a
      coordinated fashion on the slippery surface. Upon change from straight to curve
      walking, the stride length for the inside legs shortens and the vector of
      movement of the inner legs changes to pull the animal into the curve, while the
      outer legs act to pull and push it into the turn. In the reduced two-leg and in
      the single-leg preparation the behavior of the legs remained largely unchanged in
      the behavioral contexts of straight walking or turning with only small changes in
      the extreme positions. This suggests that the single stepping legs perform given
      motor programs on the slippery surface in a fashion that is highly independent
      not only of mechanical coupling between but also of the presence of the other
      legs.

PMID- 19112139
TI  - Orientation in a crowded environment: can King Penguin (Aptenodytes patagonicus)
      chicks find their creches after a displacement?
AB  - For seabird species, the presence of conspecifics in a crowded breeding colony
      can obstruct locally available orientation cues. Thus, navigation to specific
      locations can present a challenging problem. We investigated short-range
      orientation in King Penguin (Aptenodytes patagonicus) chicks that live in a large
      and densely populated colony. The two main objectives were to determine whether
      chicks displaced to a novel location away from the colony (i) can orient towards
      the colony and return to their creche and (ii) rely on visual or non-visual cues
      for orientation. To address these questions, a circular arena was constructed 100
      m away from the colony. Chicks were released in the arena during the day and at
      night. After the orientation experiment in the arena, chicks were allowed to
      return to their home creche, if they could. Our results showed that, during day
      trials, chicks preferred the half of the arena closer to the colony, but not at
      night. However, at night, birds spent more time on ;the colony half' of the arena
      if the wind blew from the colony direction. When animals were allowed to leave
      the arena, 98% of chicks homed during the day but only 62% of chicks homed at
      night. Chicks that homed at night also took longer to find their creche. The
      experiments suggest that King Penguin chicks can find their creche from a novel
      location. Visual cues are important for homing but, when visual cues are not
      present, animals are able to make use of other information carried by the wind.

PMID- 19112141
TI  - Food deprivation during photosensitive and photorefractory life-history stages
      affects the reproductive cycle in the migratory Red-headed Bunting (Emberiza
      bruniceps).
AB  - In a seasonally breeding bird species, food deprivation affects reproduction. A
      key question is whether food shortage at any time in the year will affect
      reproduction even though the food supply subsequently becomes adequate. A
      prediction would be that a food supply that is of shorter duration than that
      optimally required during a life-history stage will have consequential effects on
      the succeeding life-history stages. Two experiments investigated this in
      gonadally regressed migratory Red-headed Bunting (Emberiza bruniceps) at two life
      history stages: photosensitive and photorefractory. Experiment 1 employed two
      groups of photosensitive birds, and experiment 2 employed two groups of
      photorefractory birds. In both the experiments, birds were exposed for 8 weeks to
      a neutral day length at dim light intensity (12 h light: 12 h darkness, 12L:12D;
      L= approximately 5 lux, D=0 lux) with restricted feeding regimes (6 h food
      present: 18 h food absent, P:A 6:18 or P:A 12:12) and subsequently maintained for
      another 13 weeks at a highly stimulatory day length (16L:8D; L=400 lux; D=0 lux)
      with food ad libitum. We report that the pretreatment with restricted food cycles
      influenced the subsequent photoperiodic induction of reproductive (testis growth
      and molt) but not of metabolic (body fattening and mass gain) functions. The
      testicular response cycle under 16L:8D had a significantly lower amplitude in
      birds pretreated with P:A 6:18 than with P:A 12:12. Similarly, the recovery of
      photosensitivity was slower in photorefractory birds pretreated with P:A 6:18
      than with P:A 12:12 food cycles. Overall, our findings show for the first time in
      a seasonally breeding vertebrate species that food deprivation during non
      breeding periods of the annual cycle can affect reproductive functions later in
      the year.

PMID- 19112140
TI  - O2 store management in diving emperor penguins.
AB  - In order to further define O(2) store utilization during dives and understand the
      physiological basis of the aerobic dive limit (ADL, dive duration associated with
      the onset of post-dive blood lactate accumulation), emperor penguins (Aptenodytes
      forsteri) were equipped with either a blood partial pressure of oxygen (P(O(2)))
      recorder or a blood sampler while they were diving at an isolated dive hole in
      the sea ice of McMurdo Sound, Antarctica. Arterial P(O(2)) profiles (57 dives)
      revealed that (a) pre-dive P(O(2)) was greater than that at rest, (b) P(O(2))
      transiently increased during descent and (c) post-dive P(O(2)) reached that at
      rest in 1.92+/-1.89 min (N=53). Venous P(O(2)) profiles (130 dives) revealed that
      (a) pre-dive venous P(O(2)) was greater than that at rest prior to 61% of dives,
      (b) in 90% of dives venous P(O(2)) transiently increased with a mean maximum
      P(O(2)) of 53+/-18 mmHg and a mean increase in P(O(2)) of 11+/-12 mmHg, (c) in
      78% of dives, this peak venous P(O(2)) occurred within the first 3 min, and (d)
      post-dive venous P(O(2)) reached that at rest within 2.23+/-2.64 min (N=84).
      Arterial and venous P(O(2)) values in blood samples collected 1-3 min into dives
      were greater than or near to the respective values at rest. Blood lactate
      concentration was less than 2 mmol l(-1) as far as 10.5 min into dives, well
      beyond the known ADL of 5.6 min. Mean arterial and venous P(N(2)) of samples
      collected at 20-37 m depth were 2.5 times those at the surface, both being 2.1+/
      0.7 atmospheres absolute (ATA; N=3 each), and were not significantly different.
      These findings are consistent with the maintenance of gas exchange during dives
      (elevated arterial and venous P(O(2)) and P(N(2)) during dives), muscle ischemia
      during dives (elevated venous P(O(2)), lack of lactate washout into blood during
      dives), and arterio-venous shunting of blood both during the surface period
      (venous P(O(2)) greater than that at rest) and during dives (arterialized venous
      P(O(2)) values during descent, equivalent arterial and venous P(N(2)) values
      during dives). These three physiological processes contribute to the transfer of
      the large respiratory O(2) store to the blood during the dive, isolation of
      muscle metabolism from the circulation during the dive, a decreased rate of blood
      O(2) depletion during dives, and optimized loading of O(2) stores both before and
      after dives. The lack of blood O(2) depletion and blood lactate elevation during
      dives beyond the ADL suggests that active locomotory muscle is the site of tissue
      lactate accumulation that results in post-dive blood lactate elevation in dives
      beyond the ADL.

PMID- 19112142
TI  - Peak energy turnover in lactating European hares: the role of fat reserves.
AB  - European hares (Lepus europaeus) in central Europe have high energetic costs of
      reproduction, mainly due to precocial, rapidly growing young that rely largely on
      energy-rich milk. Thus, hares in this climate build up large fat stores during
      winter that are then gradually depleted during the spring-to-autumn breeding
      season. We hypothesized that the diminishing fat stores of females over the
      breeding season might affect resource allocation, peak energy assimilation during
      lactation or the total investment in offspring. Therefore, we measured energy
      intake, milk quality and milk production throughout lactation in spring, summer
      and autumn in females raising (size-manipulated) litters with three young each,
      under a natural photoperiod but at buffered ambient temperatures inside our
      facility. Over the course of the breeding season, the amount of milk production
      remained constant, but the fat content of the milk decreased. Hence, total energy
      transfer to young decreased significantly in autumn. By using undecanoic acid as
      a tracer of body fat mobilization, we were able to show that milk fat partially
      originated from maternal fat stores, particularly in spring. The peak sustained
      energy assimilation rates of lactating females were significantly higher in
      autumn, due to increased rates of food intake. We conclude that fat stores allow
      female hares to downregulate energy intake and expenditure early in the breeding
      season, whereas late breeding forces them to reach peak energy intake levels.
      Accordingly, we suggest that in hares, peak energy turnover during lactation
      varies with the availability of fat reserves. Limits to the sustained metabolic
      rate serve as variable constraints on reproductive investment. Thus, there might
      be a trade-off in energetic costs to mothers rearing early versus late litters in
      the year.

PMID- 19112144
TI  - Localization and regulation of a facilitative urea transporter in the kidney of
      the red-eared slider turtle (Trachemys scripta elegans).
AB  - Urea is the major excretory end product of nitrogen metabolism in most chelonian
      reptiles. In the present study, we report the isolation of a 1632 base pair cDNA
      from turtle kidney with one open reading frame putatively encoding a 403-residue
      protein, the turtle urea transporter (turtle UT). The first cloned reptilian UT
      has high homology with UTs (facilitated urea transporters) cloned from
      vertebrates, and most closely resembles the UT-A subfamily. Injection of turtle
      UT cRNA into Xenopus oocytes induced a 6-fold increase in [(14)C]urea uptake that
      was inhibited by phloretin. The turtle UT mRNA expression and tissue distribution
      were examined by RT-PCR with total RNA from various tissues. Expression of turtle
      UT mRNA was restricted to the kidney, and no signal was detected in the other
      tissues, such as brain, heart, alimentary tract and urinary bladder. An
      approximately 58 kDa protein band was detected in membrane fractions of the
      kidney by western blot using an affinity-purified antibody that recognized turtle
      UT expressed in Xenopus oocytes. In an immunohistochemical study using the anti
      turtle UT antibody, UT-immunopositive cells were observed along the distal tubule
      but not in the collecting duct. In turtles under dry conditions, plasma
      osmolality and urea concentration increased, and using semi-quantitative RT-PCR
      the UT mRNA expression level in the kidney was found to increase 2-fold compared
      with control. The present results, taken together, suggest that the turtle UT
      probably contributes to urea transport in the distal tubule segments of the
      kidney in response to hyperosmotic stress under dry conditions.

PMID- 19112143
TI  - Glycogen storage and muscle glucose transporters (GLUT-4) of mice selectively
      bred for high voluntary wheel running.
AB  - To examine the evolution of endurance-exercise behaviour, we have selectively
      bred four replicate lines of laboratory mice (Mus domesticus) for high voluntary
      wheel running (;high runner' or HR lines), while also maintaining four non
      selected control (C) lines. By generation 16, HR mice ran approximately 2.7-fold
      more than C mice, mainly by running faster (especially in females), a
      differential maintained through subsequent generations, suggesting an
      evolutionary limit of unknown origin. We hypothesized that HR mice would have
      higher glycogen levels before nightly running, show greater depletion of those
      depots during their more intense wheel running, and have increased glycogen
      synthase activity and GLUT-4 protein in skeletal muscle. We sampled females from
      generation 35 at three times (photophase 07:00 h-19:00 h) during days 5-6 of
      wheel access, as in the routine selection protocol: Group 1, day 5, 16:00 h-17:30
      h, wheels blocked from 13:00 h; Group 2, day 6, 02:00 h-03:30 h (immediately
      after peak running); and Group 3, day 6, 07:00 h-08:30 h. An additional Group 4,
      sampled 16:00 h-17:30 h, never had wheels. HR individuals with the mini-muscle
      phenotype (50% reduced hindlimb muscle mass) were distinguished for statistical
      analyses comparing C, HR normal, and HR mini. HR mini ran more than HR normal,
      and at higher speeds, which might explain why they have been favored by the
      selective-breeding protocol. Plasma glucose was higher in Group 1 than in Group
      4, indicating a training effect (phenotypic plasticity). Without wheels, no
      differences in gastrocnemius GLUT-4 were observed. After 5 days with wheels, all
      mice showed elevated GLUT-4, but HR normal and mini were 2.5-fold higher than C.
      At all times and irrespective of wheel access, HR mini showed approximately three
      fold higher [glycogen] in gastrocnemius and altered glycogen synthase activity.
      HR mini also showed elevated glycogen in soleus when sampled during peak running.
      All mice showed some glycogen depletion during nightly wheel running, in muscles
      and/or liver, but the magnitude of this depletion was not large and hence does
      not seem to be limiting to the evolution of even-higher wheel running.

PMID- 19112145
TI  - Mechanical phase shifters for coherent acoustic radiation in the stridulating
      wings of crickets: the plectrum mechanism.
AB  - Male crickets produce stridulatory songs using engaged tegmina (forewings): a
      plectrum on the left sweeps along a tooth row on the right. During stridulation,
      the plectrum moves across the teeth and vibrations are amplified by the
      surrounding cells and veins, resonating at the frequency of tooth impacts. The
      advance of the plectrum on the file is controlled by an escapement mechanism so
      that passing each single tooth generates one wave of a highly tonal signal. Both
      tegmina must oscillate in phase to avoid destructive interference. But as each
      plectrum-tooth contact begins, the right and left tegmina react in opposite
      oscillatory directions. A mechanical phase shifter is part of the left tegmen and
      compensates to achieve wing oscillation synchrony. We use a new technique to
      simulate plectrum-on-file interactions: in combination with laser vibrometry,
      this technique assessed plectrum mechanics in the cricket Gryllus bimaculatus.
      Using an excised teneral file, shaped like a partial gear and moved by a motor,
      and a microscan Doppler laser vibrometer, plectrum and left-tegmen mechanics were
      explored. The results show that plectrum and harp oscillate with a phase
      difference of ca. 156 deg., a shift rather than a complete phase inversion (180
      deg.). This phase shift occurs at the site of a large wing vein (possibly A3).
      Plectrum and harp vibrate with similar fundamental frequency, therefore, plectrum
      torsion resonant frequency is important for maintaining vibration coherence. The
      mechanical aspects involved in this partial phase inversion are discussed with
      respect to the escapement mechanism. The plectrum mechanics and its implications
      in katydid stridulation are also considered.

PMID- 19112146
TI  - Spontaneous fluctuation of the resting membrane potential in Paramecium:
      amplification caused by intracellular Ca2+.
AB  - The ciliated protozoan Paramecium spontaneously changes its swimming direction in
      the absence of external stimuli. Such behavior is based on resting potential
      fluctuations, the amplitudes of which reach a few mV. When the resting potential
      fluctuation is positive and large, a spike-like depolarization is frequently
      elicited that reverses the beating of the cilia associated with directional
      changes during swimming. We aimed to study how the resting potential fluctuation
      is amplified. Simultaneous measurements of the resting potential and
      intracellular Ca(2+) ([Ca(2+)](i)) from a deciliated cell showed that positive
      potential fluctuations were frequently accompanied by a small increase in
      [Ca(2+)](i). This result suggests that Ca(2+) influx through the somatic membrane
      occurs during the resting state. The mean amplitude of the resting potential
      fluctuation was largely decreased by either an intracellular injection of a
      calcium chelater (BAPTA) or by an extracellular addition of Ba(2+). Hence, a
      small increase in [Ca(2+)](i) amplifies the resting potential fluctuation.
      Simulation analysis of the potential fluctuation was made by assuming that Ca(2+)
      and K(+) channels of surface membrane are fluctuating between open and closed
      states. The simulated fluctuation increased to exhibit almost the same amplitude
      as the measured fluctuation using the assumption that a small Ca(2+) influx
      activates Ca(2+) channels in a positive feedback manner.

PMID- 19112147
TI  - Caudal fin shape modulation and control during acceleration, braking and backing
      maneuvers in bluegill sunfish, Lepomis macrochirus.
AB  - Evolutionary patterns of intrinsic caudal musculature in ray-finned fishes show
      that fine control of the dorsal lobe of the tail evolved first, followed by the
      ability to control the ventral lobe. This progression of increasing
      differentiation of musculature suggests specialization of caudal muscle roles.
      Fine control of fin elements is probably responsible for the range of fin
      conformations observed during different maneuvering behaviors. Here, we examine
      the kinematics of the caudal fin and the motor activity of the intrinsic caudal
      musculature during kick-and-glide, braking and backing maneuvers, and compare
      these data with our previous work on the function of the caudal fin during steady
      swimming. Kick-and-glide maneuvers consisted of large-amplitude, rapid lateral
      excursion of the tail fin, followed by forward movement of the fish with the
      caudal fin rays adducted to reduce surface area and with the tail held in line
      with the body. Just before the kick, the flexors dorsalis and ventralis,
      hypochordal longitudinalis, infracarinalis and supracarinalis showed strong
      activity. During braking, the dorsal and ventral lobes of the tail moved in
      opposite directions, forming an ;S'-shape, accompanied by strong activity in the
      interradialis muscles. During backing up, the ventral lobe initiated a dorsally
      directed wave along the distal edge of the caudal fin. The relative timing of the
      intrinsic caudal muscles varied between maneuvers, and their activation was
      independent of the activity of the red muscle of the axial myomeres in the caudal
      region. There was no coupling of muscle activity duration and electromyographic
      burst intensity in the intrinsic caudal muscles during maneuvers, as was observed
      in previous work on steady swimming. Principal-component analysis produced four
      components that cumulatively explained 73.6% of the variance and segregated kick
      and-glide, braking and backing maneuvers from each other and from steady
      swimming. The activity patterns of the intrinsic caudal muscles during
      maneuvering suggest motor control independent from myotomal musculature, and
      specialization of individual muscles for specific kinematic roles.

PMID- 19112148
TI  - Occludin and hydromineral balance in Xenopus laevis.
AB  - To investigate the response of the tight junction (TJ) protein occludin to
      environmental change in an anuran amphibian, we examined occludin tissue
      distribution, immunolocalization and alterations in mRNA expression in African
      clawed frogs (Xenopus laevis) acclimated to brackish water (BW) conditions (from
      freshwater to 2 per thousand, 5 per thousand or 10 per thousand salt water).
      Occludin mRNA is widely expressed in Xenopus and is abundant in tissues involved
      in regulating salt and water balance, such as the gastrointestinal (GI) tract,
      kidney and urinary bladder. Immunohistochemical analyses revealed strong occludin
      immunolabelling in the apicolateral region of epithelia lining the GI tract and
      mRNA expression increased along the longitudinal axis of the gut. In kidney
      tissue, occludin was differentially expressed on the luminal side of the nephron
      tubule, appearing in the distal tubules and collecting ducts only. In response to
      BW acclimation, Xenopus exhibited a significant loss of tissue water as well as
      salinity-dependent elevations in serum osmolality as a result of increased urea
      levels followed by elevated serum Na(+) and Cl(-) levels. Tissue-specific
      alterations in the ionomotive enzyme Na(+),K(+)-ATPase were also observed in
      Xenopus in response to BW acclimation. Most notably, Na(+),K(+)-ATPase activity
      in the rectum increased in response to elevated environmental salt concentrations
      while renal activity decreased. Furthermore, acclimation to BW caused tissue
      specific and salinity-dependent alterations in occludin mRNA expression within
      select Xenopus osmoregulatory organs. Taken together, these studies suggest that
      alterations in occludin, in conjunction with active transport processes, may
      contribute to amphibian hydromineral homeostasis during environmental change.

PMID- 19112149
TI  - Bioenergetics and inter-individual variation in physiological capacities in a
      relict mammal - the Monito del Monte (Dromiciops gliroides).
AB  - In evolutionary physiology, studies of inter-individual variation (i.e.
      repeatability) in functional capacities are valuable as they indicate - within
      populations - what attributes could respond to natural selection. Although
      repeatability and quantitative genetics of physiological traits in energy
      metabolism of eutherian mammals have been well characterized, few or no studies
      have been performed on marsupials. We studied the repeatability (i.e. intraclass
      correlation coefficient, tau) of bioenergetics for Monito del Monte (Dromiciops
      gliroides), the sole living representative of an otherwise extinct marsupial
      order (Microbiotheria). We measured resting metabolic rate as CO(2) production
      (V(CO(2))) and O(2) consumption (V(O(2))) simultaneously, together with minimum
      thermal conductance (C), evaporative water loss (EWL) and respiratory quotient
      (RQ), in a sample of ca. 20 individuals. Our results suggest that D. gliroides
      exhibits poor control of body temperature (T(b)), with a thermal amplitude of ca.
      10 degrees C in normothermia. As a consequence, repeatability of T(b) and
      metabolic rate (either as V(CO(2)) or V(O(2))) were relatively low
      (tau(T)(b)=0.25+/-0.04, tau(VCO2)=0.14+/-0.03, tau(V)(O2)=0.24+/-0.02, jackknife
      estimations of standard errors). Thermal conductance exhibited near-zero or
      negative repeatability and was lower than expected for marsupials. However, we
      found significant repeatability for RQ and EWL (tau=0.32+/-0.03 and 0.49+/-0.09,
      respectively). In general, these results suggest that Monito del Monte exhibits
      some ;reptilian' physiological characteristics. The relatively low repeatability
      of physiological variables, which otherwise exhibit large inter-individual and
      genetic variance in eutherian mammals, suggests that these capacities do not
      exhibit evolutionary potential in the ancient order Microbiotheria.

PMID- 19112150
TI  - Freeze tolerance in an arctic Alaska stonefly.
AB  - Most aquatic insects do not survive subzero temperatures and, for those that do,
      the physiology has not been well characterized. Nemoura arctica is a species of
      stonefly widely distributed throughout arctic and subarctic Alaska. We collected
      nymphs from the headwaters of the Chandalar River, where we recorded streambed
      temperatures as low as -12.7 degrees C in midwinter. When in contact with ice,
      autumn-collected N. arctica cool to -1.5+/-0.4 degrees C before freezing, but
      individuals survived temperatures as low as -15 degrees C, making this the first
      described species of freeze-tolerant stonefly. N. arctica clearly survive
      freezing in nature, as winter-collected nymphs encased in ice demonstrated high
      survivorship when thawed. In the laboratory, 87% of N. arctica nymphs frozen to 
      15 degrees C for 2.5 weeks survived and, within one month of thawing, 95% of the
      last-instar nymphs emerged. N. arctica produce both glycerol and ice-binding
      factors (e.g. antifreeze protein) in response to low temperature. Hemolymph
      glycerol concentrations increased from 3 mmol l(-1) to 930+/-114 mmol l(-1) when
      temperatures were decreased from 4 degrees C to -8 degrees C, and N. arctica
      continued to produce glycerol even while frozen. Although the hemolymph of
      individual cold-acclimated nymphs occasionally exhibited more than a degree of
      thermal hysteresis, typically the hemolymph exhibited only hexagonal crystal
      growth, indicating a low concentration of ice-binding factor. Hemolymph of nymphs
      acclimated to subzero temperatures had recrystallization inhibition. These
      results demonstrate that, in the face of freezing conditions, N. arctica exhibit
      overwintering adaptations similar to those of terrestrial insects.

PMID- 19112151
TI  - The cardiac response of the crab Chasmagnathus granulatus as an index of sensory
      perception.
AB  - When an animal's observable behavior remains unaltered, one can be misled in
      determining whether it is able to sense an environmental cue. By measuring an
      index of the internal state, additional information about perception may be
      obtained. We studied the cardiac response of the crab Chasmagnathus to different
      stimulus modalities: a light pulse, an air puff, virtual looming stimuli and a
      real visual danger stimulus. The first two did not trigger observable behavior,
      but the last two elicited a clear escape response. We examined the changes in
      heart rate upon sensory stimulation. Cardiac response and escape response
      latencies were also measured and compared during looming stimuli presentation.
      The cardiac parameters analyzed revealed significant changes (cardio-inhibitory
      responses) to all the stimuli investigated. We found a clear correlation between
      escape and cardiac response latencies to different looming stimuli. This study
      proved useful to examine the perceptual capacity independently of behavior. In
      addition, the correlation found between escape and cardiac responses support
      previous results which showed that in the face of impending danger the crab
      triggers several coordinated defensive reactions. The ability to escape predation
      or to be alerted to subtle changes in the environment in relation to autonomic
      control is associated with the complex ability to integrate sensory information
      as well as motor output to target tissues. This ;fear, fight or flight' response
      gives support to the idea of an autonomic-like reflexive control in crustaceans.

PMID- 19112153
TI  - Metabotropic glutamate 1 receptor: current concepts and perspectives.
AB  - Almost 25 years after the first report that glutamate can activate receptors
      coupled to heterotrimeric G-proteins, tremendous progress has been made in the
      field of metabotropic glutamate receptors. Now, eight members of this family of
      glutamate receptors, encoded by eight different genes that share distinctive
      structural features have been identified. The first cloned receptor, the
      metabotropic glutamate (mGlu) receptor mGlu1 has probably been the most
      extensively studied mGlu receptor, and in many respects it represents a
      prototypical subtype for this family of receptors. Its biochemical, anatomical,
      physiological, and pharmacological characteristics have been intensely
      investigated. Together with subtype 5, mGlu1 receptors constitute a subgroup of
      receptors that couple to phospholipase C and mobilize Ca(2+) from intracellular
      stores. Several alternatively spliced variants of mGlu1 receptors, which differ
      primarily in the length of their C-terminal domain and anatomical localization,
      have been reported. Use of a number of genetic approaches and the recent
      development of selective antagonists have provided a means for clarifying the
      role played by this receptor in a number of neuronal systems. In this article we
      discuss recent advancements in the pharmacology and concepts about the
      intracellular transduction and pathophysiological role of mGlu1 receptors and
      review earlier data in view of these novel findings. The impact that this new and
      better understanding of the specific role of these receptors may have on novel
      treatment strategies for a variety of neurological and psychiatric disorders is
      considered.

PMID- 19112155
TI  - LBNP exercise protects aerobic capacity and sprint speed of female twins during
      30 days of bed rest.
AB  - We have shown previously that treadmill exercise within lower body negative
      pressure (LBNPex) maintains upright exercise capacity (peak oxygen consumption,
      Vo(2peak)) in men after 5, 15, and 30 days of bed rest (BR). We hypothesized that
      LBNPex protects treadmill Vo(2peak) and sprint speed in women during a 30-day BR.
      Seven sets of female monozygous twins volunteered to participate. Within each
      twin set, one was randomly assigned to a control group (Con) and performed no
      countermeasures, and the other was assigned to an exercise group (Ex) and
      performed a 40-min interval (40-80% pre-BR Vo(2peak)) LBNPex (51 +/- 5 mmHg)
      protocol, plus 5 min of static LBNP, 6 days per week. Before and immediately
      after BR, subjects completed a 30.5-m sprint test and an upright graded treadmill
      test to volitional fatigue. These results in women were compared with previously
      reported reductions in Vo(2peak) and sprint speed in male twins after BR. In
      women, sprint speed (-8 +/- 2%) and Vo(2peak) (-6 +/- 2%) were not different
      after BR in the Ex group. In contrast, both sprint speed (-24 +/- 5%) and
      Vo(2peak) (-16 +/- 3%) were significantly less after BR in the Con group. The
      effect of BR on sprint speed and Vo(2peak) after BR was not different between
      women and men. We conclude that treadmill exercise within LBNP protects against
      BR-induced reductions in Vo(2peak) and sprint speed in women and should prove
      effective during long-duration spaceflight.

PMID- 19112156
TI  - Effects of static and dynamic training on the stiffness and blood volume of
      tendon in vivo.
AB  - The purpose of this study was to investigate the effects of static and dynamic
      training on the stiffness and blood volume of the human tendon in vivo. Ten
      subjects completed 12 wk (4 days/wk) of a unilateral training program for knee
      extensors. They performed static training on one side [ST; 70% of maximum
      voluntary contraction (MVC)] and dynamic training on the other side (DT; 80% of
      one repetition maximum). Before and after training, MVC, neural activation level
      (by interpolated twitch), muscle volume (by magnetic resonance imaging),
      stiffness of tendon-aponeurosis complex and patella tendon (by ultrasonography),
      and blood volume of patella tendon (by red laser lights) were measured. Both
      protocols significantly increased MVC (49% for ST, 32% for DT; both P < 0.001),
      neural activation level (9.5% for ST, 7.6% for DT; both P < 0.01), and muscle
      volume (4.5% for ST, 5.6% for DT; both P < 0.01). The stiffness of tendon
      aponeurosis complex increased significantly after ST (55%; P = 0.003) and DT
      (30%; P = 0.033), while the stiffness of patella tendon increased significantly
      after ST (83%; P < 0.001), but not for DT (P = 0.110). The blood volume of
      patella tendon increased significantly after DT (47%; P = 0.016), but not for ST
      (P = 0.205). These results implied that the changes in the blood volume of tendon
      would be related to differences in the effects of resistance training on the
      tendon properties.

PMID- 19112157
TI  - Influence of acute exercise with and without carbohydrate replacement on
      postprandial lipid metabolism.
AB  - Acute exercise, undertaken on the day before an oral fat tolerance test (OFTT),
      typically reduces postprandial triglycerides (TG) and increases high-density
      lipoprotein-cholesterol (HDL-C). However, the benefits of acute exercise may be
      overstated when studies do not account for compensatory changes in dietary
      intake. The objective of this study was to determine the influence of acute
      exercise, with and without carbohydrate (CHO) replacement, on postprandial lipid
      metabolism. Eight recreationally active young men underwent an OFTT on the
      morning after three experimental conditions: no exercise [control (Con)],
      prolonged exercise without CHO replacement (Ex-Def) and prolonged exercise with
      CHO replacement to restore CHO and energy balance (Ex-Bal). The exercise session
      in Ex-Def and Ex-Bal consisted of 90 min cycle ergometry at 70% peak oxygen
      uptake (Vo(2peak)) followed by 10 maximal 1-min sprints. CHO replacement was
      achieved using glucose solutions consumed at 0, 2, and 4 h postexercise. Muscle
      glycogen was 40 +/- 4% (P < 0.05) and 94 +/- 3% (P = 0.24) of Con values on the
      morning of the Ex-Def and Ex-Bal OFTT, respectively. Postprandial TG were 40 +/-
      14% lower and postprandial HDL-C, free fatty acids, and 3-hydroxybutyrate were
      higher in Ex-Def compared with Con (P < 0.05). Most importantly, these exercise
      effects were not evident in Ex-Bal. Postprandial insulin and glucose and the
      homeostatic model assessment of insulin resistance (HOMA(IR)) were not
      significantly different across trials. There was no relation between the changes
      in postprandial TG and muscle glycogen across trials. In conclusion, the
      influence of acute exhaustive exercise on postprandial lipid metabolism is
      largely dependent on the associated CHO and energy deficit.

PMID- 19112158
TI  - Maximal lengthening contractions induce different signaling responses in the type
      I and type II fibers of human skeletal muscle.
AB  - The molecular mechanisms by which resistance exercise enlarges muscle mass,
      particularly the mass of fast-twitch type II fibers, are likely to involve
      enhanced phosphorylation/activation of key enzymes regulating protein synthesis.
      The hypothesis is that resistance exercise influences the phosphorylation of such
      key signaling proteins to a greater extent in type II than in type I fibers. Six
      recreationally active male subjects performed four sets of six maximal
      lengthening contractions with one leg. Muscle biopsies were taken from the vastus
      lateralis before and immediately after exercise and following 1 and 2 h of
      recovery. Samples were freeze-dried, and individual muscle fibers were dissected
      out and identified as type I or type II after staining for myosin ATPase.
      Phosphorylation of p70(S6k) on Thr(389) and S6 in type II fibers was increased
      three-to fourfold and six- to ninefold (P < 0.05), respectively, 1 and 2 h after
      exercise, whereas phosphorylation in type I fibers remained unchanged.
      Phosphorylation of Akt, mammalian target of rapamycin (mTOR) and AMP-activated
      protein kinase (AMPK) was unaltered in both fiber types, whereas that of
      eukaryotic elongation factor 2 (eEF2) was attenuated 20-45% (P < 0.05) in type II
      fibers during recovery. Phosphorylation of ERK1/2 was elevated six- to sevenfold
      (P < 0.05) immediately after exercise, and p38 MAPK phosphorylation was increased
      three- to fourfold (P < 0.05) for as long as 1 h after exercise in both types of
      fibers, although the level was markedly higher in type II fibers (P < 0.05). In
      conclusion, the elevation of p70(S6k) and the reduction of eEF2 phosphorylation
      in the type II fibers following resistance exercise suggest stimulation of
      protein synthesis, which may contribute to a more pronounced enlargement of these
      fibers. Our findings also suggest that p70(S6k) is activated, at least in part,
      via pathways not involving Akt-mTOR and MAPK.

PMID- 19112159
TI  - Mass loading of the upper airway extraluminal tissue space in rabbits: effects on
      tissue pressure and pharyngeal airway lumen geometry.
AB  - Lateral pharyngeal fat pad compression of the upper airway (UA) wall is thought
      to influence UA size in patients with obstructive sleep apnea. We examined
      interactions between acute mass/volume loading of the UA extra-luminal tissue
      space and UA patency. We studied 12 supine, anesthetized, spontaneously
      breathing, head position-controlled (50 degrees ), New Zealand White rabbits.
      Submucosal extraluminal tissue pressures (ETP) in the anterolateral (ETPlat) and
      anterior (ETPant) pharyngeal wall were monitored with surgically inserted
      pressure transducer-tipped catheters (Millar). Tracheal pressure (Ptr) and
      airflow (V) were measured via a pneumotachograph and pressure transducer inserted
      in series into the intact trachea, with hypopharyngeal cross-sectional area (CSA)
      measured via computed tomography, while graded saline inflation (0-1.5ml) of a
      compliant tissue expander balloon in the anterolateral subcutaneous tissue was
      performed. Inspiratory UA resistance (Rua) at 20 ml/s was calculated from a power
      function fitted to Ptr vs. V data. Graded expansion of the anterolateral balloon
      increased ETPlat from 2.3 +/- 0.5 cmH(2)O (n = 11, mean +/- SEM) to 5.0 +/- 1.1
      cmH(2)O at 1.5-ml inflation (P < 0.05; ANOVA). However, ETPant was unchanged from
      0.5 +/- 0.5 cmH(2)O (n = 9; P = 0.17). Concurrently, Rua increased to 119 +/-
      4.2% of baseline value (n = 12; P < 0.001) associated with a significant
      reduction in CSA between 10 and 70% of airway length to a minimum of 82.2 +/-
      4.4% of baseline CSA at 40% of airway length (P < 0.05). We conclude that
      anterolateral loading of the upper airway extraluminal tissue space decreases
      upper airway patency via an increase in ETPlat, but not ETPant. Lateral
      pharyngeal fat pad size may influence UA patency via increased tissue volume and
      pressure causing UA wall compression.

PMID- 19112160
TI  - Muscle metabolism and acid-base status during exercise in forearm work-related
      myalgia measured with 31P-MRS.
AB  - In this study, we examined muscle metabolic and acid-base status during
      incremental wrist extension exercise in the forearm of individuals with work
      related myalgia (WRM). Eighteen women employed in full-time occupations involving
      repetitive forearm labor were recruited in this cross-sectional study. Nine of
      these women were diagnosed with WRM, while the other nine had no previous WRM
      history and were used as age-matched controls (Con). Phosphorus-31 magnetic
      resonance spectroscopy ((31)P-MRS) was used to noninvasively monitor the
      intracellular concentrations of phosphocreatine ([PCr]) and inorganic phosphate
      ([P(i)]) as well as intracellular pH (pH(i)) status during exercise in WRM and
      Con. We observed a 38% decreased work capacity in WRM compared with Con [0.18 W
      (SD 0.03) vs. 0.28 W (SD 0.10); P = 0.007]. Piecewise linear regression of the
      incremental exercise data revealed that the onset of a faster decrease in pH(i)
      (i.e., the pH threshold, pHT) and the onset of a faster increase in
      log([P(i)]/[PCr]) (i.e., the phosphorylation threshold, PT) occurred at a 14%
      relatively lower power output in WRM [pHT: 45.2% (SD 5.3) vs. 59.0% (SD 4.6), P <
      0.001; PT: 44.8% (SD 4.3) vs. 57.8% (SD 3.1), P < 0.001; % of peak power output,
      Con vs. WRM, respectively]. Monoexponential modeling of the kinetics of [PCr] and
      pH(i) recovery following exercise demonstrated a slower (P = 0.005) time constant
      (tau) for [PCr] in WRM [113 s (SD 25)] vs. Con [77 s (SD 23)] and a slower (P =
      0.007) tau for pH(i) in WRM [370 s (SD 178)] vs. Con [179 s (SD 52)]. In
      conclusion, our results suggest that WRM is associated with an increased reliance
      on nonoxidative metabolism. Possible mechanisms include a reduction in local
      muscle blood flow and perfusion, an increased ATP cost of force production, or
      both.

PMID- 19112161
TI  - Brief intense interval exercise activates AMPK and p38 MAPK signaling and
      increases the expression of PGC-1alpha in human skeletal muscle.
AB  - From a cell signaling perspective, short-duration intense muscular work is
      typically associated with resistance training and linked to pathways that
      stimulate growth. However, brief repeated sessions of sprint or high-intensity
      interval exercise induce rapid phenotypic changes that resemble traditional
      endurance training. We tested the hypothesis that an acute session of intense
      intermittent cycle exercise would activate signaling cascades linked to
      mitochondrial biogenesis in human skeletal muscle. Biopsies (vastus lateralis)
      were obtained from six young men who performed four 30-s "all out" exercise bouts
      interspersed with 4 min of rest (<80 kJ total work). Phosphorylation of AMP
      activated protein kinase (AMPK; subunits alpha1 and alpha2) and the p38 mitogen
      activated protein kinase (MAPK) was higher (P <or= 0.05) immediately after bout 4
      vs. preexercise. Peroxisome proliferator-activated receptor-gamma coactivator
      1alpha (PGC-1alpha) mRNA was increased approximately twofold above rest after 3 h
      of recovery (P <or= 0.05); however, PGC-1alpha protein content was unchanged. In
      contrast, phosphorylation of protein kinase B/Akt (Thr(308) and Ser(473)) tended
      to decrease, and downstream targets linked to hypertrophy (p70 ribosomal S6
      kinase and 4E binding protein 1) were unchanged after exercise and recovery. We
      conclude that signaling through AMPK and p38 MAPK to PGC-1alpha may explain in
      part the metabolic remodeling induced by low-volume intense interval exercise,
      including mitochondrial biogenesis and an increased capacity for glucose and
      fatty acid oxidation.

PMID- 19112162
TI  - Lung mechanical and vascular changes during positive- and negative-pressure lung
      inflations: importance of reference pressures in the pulmonary vasculature.
AB  - The continuous changes in lung mechanics were related to those in pulmonary
      vascular resistance (Rv) during lung inflations to clarify the mechanical changes
      in the bronchoalveolar system and the pulmonary vasculature. Rv and low-frequency
      lung impedance data (Zl) were measured continuously in isolated, perfused rat
      lungs during 2-min inflation-deflation maneuvers between transpulmonary pressures
      of 2.5 and 22 cmH(2)O, both by applying positive pressure at the trachea and by
      generating negative pressure around the lungs in a closed box. ZL was averaged
      and evaluated for 2-s time windows; airway resistance (Raw), parenchymal damping
      and elastance (H) were determined in each window. Lung inflation with positive
      and negative pressures led to very similar changes in lung mechanics, with
      maximum decreases in Raw [-68 +/- 4 (SE) vs. -64 +/- 18%] and maximum increases
      in H (379 +/- 36 vs. 348 +/- 37%). Rv, however, increased with positive inflation
      pressure (15 +/- 1%), whereas it exhibited mild decreases during negative
      pressure expansions (-3 +/- 0.3%). These results demonstrate that pulmonary
      mechanical changes are not affected by the opposing modes of lung inflations and
      confirm the importance of relating the pulmonary vascular pressures in
      interpreting changes in Rv.

PMID- 19112163
TI  - Angiopoietin-2 exocytosis is stimulated by sphingosine-1-phosphate in human blood
      and lymphatic endothelial cells.
AB  - OBJECTIVE: Although diverse functions of angiopoietin-2 (Ang2) have been
      revealed, little is known about upstream signaling molecules regulating Ang2
      exocytosis. We therefore investigated the mechanism of Ang2 exocytosis in human
      blood and lymphatic endothelial cells (BECs and LECs) by stimulation with
      sphingosine-1-phosphate (S1P). METHODS AND RESULTS: By immunostaining and ELISA
      analyses using our newly developed human Ang2-specific antibodies, Ang2
      exocytosis from human endothelial cells was examined. Both exogenous and
      endogenous S1P trigger rapid Ang2 exocytosis in time- and dose-dependent manners.
      Intriguingly, S1P-induced Ang2 exocytosis is higher in LECs than BECs. These
      effects of S1P are mainly mediated by the endothelial differentiation gene
      receptor 1, which subsequently activates its downstream phospholipase C and
      intracellular calcium mobilization to trigger Ang2 exocytosis. Consistently, S1P
      also dramatically stimulates Ang2 exocytosis from the ECs of ex vivo-incubated
      blood vessels. CONCLUSION: These results imply that the rapid secretion of Ang2
      by exocytosis from endothelial cells is another possible mechanism underlying S1P
      induced angiogenesis and inflammation.

PMID- 19112164
TI  - Early growth response-1 regulates angiopoietin-1-induced endothelial cell
      proliferation, migration, and differentiation.
AB  - OBJECTIVE: Angiopoietin-1 (Ang-1) is an important regulator of angiogenesis in
      endothelial cells. It promotes migration, proliferation, and differentiation of
      cells, although the regulating factors involved in these processes remain
      unclear. In this study, we evaluated the contribution of the transcription factor
      early growth response-1 (Egr-1) to Ang-1-induced angiogenesis in human umbilical
      vein endothelial cells (HUVECs). METHODS AND RESULTS: Expression of Egr-1 was
      evaluated with real-time PCR and immunoblotting, whereas Egr-1 DNA binding
      activity was monitored with electrophoretic mobility shift assays. Cell migration
      was measured with wound healing and Boyden chamber assays, whereas cell
      proliferation and differentiation of cells into capillary-like tube structures
      were monitored with cell counting, BrdU incorporation and Matrigels. To
      selectively inhibit Egr-1 expression, we used both siRNA oligonucleotides and
      specific DNAzymes. Egr-1 mRNA expression rose approximately 9-fold within 2 hours
      of Ang-1 exposure and declined thereafter. Upregulation of Egr-1 expression was
      accompanied by an increase in nuclear mobilization and augmented DNA binding.
      These processes were mediated through the Erk1/2, PI-3 kinase/AKT, and mTOR
      pathways. Knockdown of Egr-1 expression completely abrogated Ang-1-induced
      endothelial migration and significantly reduced proliferation and capillary-like
      tube formation of HUVECs that overexpress Ang-1. CONCLUSIONS: Ang-1 triggers
      significant and transient induction of Egr-1, and Egr-1 contributes to Ang-1
      induced endothelial cell migration and proliferation.

PMID- 19112152
TI  - Chemistry and antihypertensive effects of tempol and other nitroxides.
AB  - Nitroxides can undergo one- or two-electron reduction reactions to hydroxylamines
      or oxammonium cations, respectively, which themselves are interconvertible,
      thereby providing redox metabolic actions. 4-Hydroxy-2,2,6,6
      tetramethylpiperidine-N-oxyl (tempol) is the most extensively studied nitroxide.
      It is a cell membrane-permeable amphilite that dismutates superoxide
      catalytically, facilitates hydrogen peroxide metabolism by catalase-like actions,
      and limits formation of toxic hydroxyl radicals produced by Fenton reactions. It
      is broadly effective in detoxifying these reactive oxygen species in cell and
      animal studies. When administered intravenously to hypertensive rodent models,
      tempol caused rapid and reversible dose-dependent reductions in blood pressure in
      22 of 26 studies. This was accompanied by vasodilation, increased nitric oxide
      activity, reduced sympathetic nervous system activity at central and peripheral
      sites, and enhanced potassium channel conductance in blood vessels and neurons.
      When administered orally or by infusion over days or weeks to hypertensive rodent
      models, it reduced blood pressure in 59 of 68 studies. This was accompanied by
      correction of salt sensitivity and endothelial dysfunction and reduced agonist
      evoked oxidative stress and contractility of blood vessels, reduced renal
      vascular resistance, and increased renal tissue oxygen tension. Thus, tempol is
      broadly effective in reducing blood pressure, whether given by acute intravenous
      injection or by prolonged administration, in a wide range of rodent models of
      hypertension.

PMID- 19112165
TI  - Platelet activation by low concentrations of intact oxidized LDL particles
      involves the PAF receptor.
AB  - OBJECTIVE: Mitochondrial depolarization aids platelet activation. Oxidized LDL
      (oxLDL) contains the medium length oxidatively truncated phospholipid hexadecyl
      azelaoyl-lysoPAF (HAz-LPAF) that disrupts mitochondrial function in nucleated
      cells, so oxLDL may augment platelet activation. METHODS AND RESULTS: Flow
      cytometry showed intact oxLDL particles synergized with subthreshold amounts of
      soluble agonists to increase intracellular Ca2+, and initiate platelet
      aggregation and surface expression of activated gpIIb/IIIa and P-selectin. oxLDL
      also induced aggregation and increased intracellular Ca2+ in FURA2-labeled cells
      by itself at low, although not higher, concentrations. HAz-LPAF, alone and in
      combination with substimulatory amounts of thrombin, rapidly increased
      cytoplasmic Ca2+ and initiated aggregation. HAz-LPAF depolarized mitochondria in
      intact platelets, but this required concentrations beyond those that directly
      activated platelets. An unexpectedly large series of chemically pure truncated
      phospholipids generated by oxidative fragmentation of arachidonoyl-,
      docosahexaneoyl-, or linoleoyl alkyl phospholipids were platelet agonists. The
      PAF receptor, thought to effectively recognize only phospholipids with very short
      sn-2 residues, was essential for platelet activation because PAF receptor
      agonists blocked signaling by all these medium length phospholipids and oxLDL.
      CONCLUSIONS: Intact oxLDL particles activate platelets through the PAF receptor,
      and the PAF receptor responds to a far wider range of oxidized phospholipids in
      oxLDL than anticipated.

PMID- 19112166
TI  - Effect of rimonabant on the high-triglyceride/ low-HDL-cholesterol dyslipidemia,
      intraabdominal adiposity, and liver fat: the ADAGIO-Lipids trial.
AB  - BACKGROUND: Rimonabant, the first selective cannabinoid type 1 (CB1) receptor
      antagonist, improves cardiometabolic risk factors in overweight/obese patients.
      ADAGIO-Lipids assessed the effect of rimonabant on cardiometabolic risk factors
      and intraabdominal and liver fat. METHODS AND RESULTS: 803 abdominally obese
      patients with atherogenic dyslipidemia (increased triglycerides [TG] or reduced
      high-density lipoprotein-cholesterol [HDL-C]) were randomized to placebo or
      rimonabant 20 mg/d for 1 year. HDL-C and TG were coprimary end points.
      Intraabdominal (visceral) and liver fat were measured by computed tomography in a
      subgroup of 231 patients. In total, 73% of rimonabant- and 70% of placebo-treated
      patients completed the study treatment. Rimonabant 20 mg produced significantly
      greater changes from baseline versus placebo in HDL-C (+7.4%) and TG levels (
      18%; P<0.0001), as well as low-density lipoprotein (LDL) and HDL particle sizes,
      apolipoprotein A1 and B, HDL2, HDL3, C-reactive protein, and adiponectin levels
      (all P<0.05). Rimonabant decreased abdominal subcutaneous adipose tissue (AT)
      cross-sectional area by 5.1% compared to placebo (P<0.005), with a greater
      reduction in visceral AT (-10.1% compared to placebo; P<0.0005), thereby reducing
      the ratio of visceral/subcutaneous AT (P<0.05). Rimonabant significantly reduced
      liver fat content (liver/spleen attenuation ratio; P<0.005). Systolic (-3.3 mm
      Hg) and diastolic (-2.4 mm Hg) blood pressure were significantly reduced with
      rimonabant versus placebo (P<0.0001). The safety profile of rimonabant was
      consistent with previous studies; gastrointestinal, nervous system, psychiatric,
      and general adverse events were more common with rimonabant 20 mg. CONCLUSIONS:
      In abdominally obese patients with atherogenic dyslipidemia, rimonabant 20 mg
      significantly improved multiple cardiometabolic risk markers and induced
      significant reductions in both intraabdominal and liver fat.

PMID- 19112167
TI  - Multi-hit inhibition of circulating and cell-associated components of the toll
      like receptor 4 pathway by oxidized phospholipids.
AB  - OBJECTIVE: Oxidized phospholipids (OxPLs) that are abundant in atherosclerotic
      lesions are increasingly recognized as context-dependent lipid mediators
      demonstrating both pro- and antiinflammatory activities. Molecular mechanisms of
      their effects are largely unknown. Here we present novel information on the
      mechanisms whereby OxPLs modulate activation of TLR4 by lipopolysaccharide (LPS).
      METHODS AND RESULTS: We show, using several cell types and various inflammatory
      genes as readouts, that different classes and molecular species of OxPLs do not
      stimulate TLR4 but exert prominent inhibitory effects on LPS-induced reactions.
      Our data demonstrate that binding of OxPLs to the LPS-binding protein (LBP) and
      CD14 prevents recognition of LPS by these proteins, thus impairing activation of
      TLR4. In addition, OxPLs inhibited LBP- and CD14-independent activation of TLR4
      by the synthetic TLR4 agonist E6020 indicating that in parallel with LBP and
      CD14, OxPLs target cell-associated steps in TLR4 cascade. CONCLUSIONS: Our data
      suggest that OxPLs inhibit action of LPS via a multi-hit mechanism. These results
      support the notion that OxPLs are endogenous inhibitors of TLR4 produced in
      response to oxidative stress.

PMID- 19112168
TI  - PeroxiBase: a powerful tool to collect and analyse peroxidase sequences from
      Viridiplantae.
AB  - Peroxidases are enzymes that are implicated in several biological processes and
      are detected in all living organisms. The increasing number of sequencing
      projects and the poor quality of annotation justified the creation of an
      efficient tool that was suitable for collecting and annotating the huge quantity
      of data. Started in 2004 to collect only class III peroxidases, PeroxiBase has
      undergone important updates since then and, currently, the majority of peroxidase
      sequences from all kingdoms of life is stored in the database. In addition, the
      web site (http://peroxibase.isb-sib.ch) provides a series of bioinformatics tools
      and facilities suitable for analysing these stored sequences. In particular, the
      high number of isoforms in each organism makes phylogenetic studies extremely
      useful to elucidate the complex evolution of these enzymes, not only within the
      plant kingdom but also between the different kingdoms. This paper provides a
      general overview of PeroxiBase, focusing on its tools and the stored data. The
      main goal is to give researchers some guidelines to extract classified and
      annotated sequences from the data base in a quick and easy way in order to
      perform alignments and phylogenetic analysis. The description of the database is
      accompanied by the updates we have recently carried out in order to improve its
      completeness and make it more user-friendly.

PMID- 19112169
TI  - Organelle motility in the pollen tube: a tale of 20 years.
AB  - Organelle movement is an evident feature of pollen tubes and is essential for the
      process of tube growth because it enables the proper distribution of organelles
      and the accumulation of secretory vesicles in the tube apex. Organelles move
      along the actin filaments through dynamic interactions with myosin but other
      proteins are probably responsible for control of this activity. The role of
      microtubules and microtubule-based motors is less clear and somewhat enigmatic.
      Nevertheless, the pollen tube is an excellent cell model in which to study and
      analyse the molecular mechanisms that drive and control organelle motility in
      relation to plant cell expansion. Current knowledge and the main scientific
      discoveries in this field of research over the last 20 years are summarized here.
      Future prospects in the study of the molecular mechanisms that mediate organelle
      transport and vesicle accumulation during pollen tube elongation are also
      discussed.

PMID- 19112170
TI  - Silencing of StKCS6 in potato periderm leads to reduced chain lengths of suberin
      and wax compounds and increased peridermal transpiration.
AB  - Very long chain aliphatic compounds occur in the suberin polymer and associated
      wax. Up to now only few genes involved in suberin biosynthesis have been
      identified. This is a report on the isolation of a potato (Solanum tuberosum) 3
      ketoacyl-CoA synthase (KCS) gene and the study of its molecular and physiological
      relevance by means of a reverse genetic approach. This gene, called StKCS6, was
      stably silenced by RNA interference (RNAi) in potato. Analysis of the chemical
      composition of silenced potato tuber periderms indicated that StKCS6 down
      regulation has a significant and fairly specific effect on the chain length
      distribution of very long-chain fatty acids (VLCFAs) and derivatives, occurring
      in the suberin polymer and peridermal wax. All compounds with chain lengths of
      C(28) and higher were significantly reduced in silenced periderms, whereas
      compounds with chain lengths of C(26) and lower accumulated. Thus, StKCS6 is
      preferentially involved in the formation of suberin and wax lipidic monomers with
      chain lengths of C(28) and higher. As a result, peridermal transpiration of the
      silenced lines was about 1.5-times higher than that of the wild type. Our results
      convincingly show that StKCS6 is involved in both suberin and wax biosynthesis
      and that a reduction of the monomeric carbon chain lengths leads to increased
      rates of peridermal transpiration.

PMID- 19112171
TI  - Efficient mitochondrial targeting relies on co-operation of multiple protein
      signals in plants.
AB  - To date, the most prevalent model for transport of pre-proteins to plant
      mitochondria is based on the activity of an N-terminal extension serving as a
      targeting peptide. Whether the efficient delivery of proteins to mitochondria is
      based exclusively on the action of the N-terminal extension or also on that of
      other protein determinants has yet to be defined. A novel mechanism is reported
      here for the targeting of a plant protein, named MITS1, to mitochondria. It was
      found that MITS1 contains an N-terminal extension that is responsible for
      mitochondrial targeting. Functional dissection of this extension shows the
      existence of a cryptic signal for protein targeting to the secretory pathway. The
      first 11 amino acids of the N-terminal extension are necessary to overcome the
      activity of this signal sequence and target the protein to the mitochondria.
      These data suggest that co-operation of multiple determinants within the N
      terminal extension of mitochondrial proteins may be necessary for efficient
      mitochondrial targeting. It was also established that the presence of a
      tryptophan residue toward the C-terminus of the protein is crucial for
      mitochondrial targeting, as mutation of this residue results in a redistribution
      of MITS1 to the endoplasmic reticulum and Golgi apparatus. These data suggest a
      novel targeting model whereby protein traffic to plant mitochondria is influenced
      by domains in the full-length protein as well as the N-terminal extension.

PMID- 19112172
TI  - Effects of top excision on the potassium accumulation and expression of potassium
      channel genes in tobacco.
AB  - The effects of the removal of the shoot apex of tobacco on the relative
      transcript levels of potassium channel genes, determined by real-time PCR, and on
      the relationship between the expression of genes encoding potassium channels and
      potassium concentration, were studied. The results from the study indicated that
      comparatively more assimilates of photosynthesis were allocated to the apex in
      control plants than in both decapitated and IAA-treated decapitated plants. By
      contrast, dry matter in the upper leaves, roots, and stems in both decapitated
      and IAA-treated plants was significantly increased relative to control plants.
      The potassium level in whole plants decreased post-decapitation compared with
      control plants, and so did the potassium concentration in middle and upper
      leaves, stem, and roots. Expression of NKT1, NtKC1, NTORK1, and NKT2 was
      inhibited by decapitation in tobacco leaves with a gradual reduction after
      decapitation, but was induced in roots. The relative expression of NKT1, NTORK1,
      and NKT2 in tobacco leaves was higher than that in roots, whereas the expression
      of NtKC1 was higher in roots. The levels of inhibition and induction of NKT1,
      NtKC1, NTORK1, and NKT2 in leaves and roots, respectively, associated with
      decapitation were reduced by the application of IAA on the cut surface of the
      decapitated stem. Further results showed that the level of endogenous auxin IAA
      in decapitated plants, which dropped in leaves and increased in roots by 140.7%
      at 14 d compared with the control plant, might be attributed to the change in the
      expression of potassium channel genes. The results suggest that there is a
      reciprocal relationship among endogenous auxin IAA, expression of potassium
      channel genes and potassium accumulation. They further imply that the endogenous
      IAA probably plays a role in regulating the expression of potassium channel
      genes, and that variations in expression of these genes affected the accumulation
      and distribution of potassium in tobacco.

PMID- 19112174
TI  - S6 kinase 1 regulates estrogen receptor alpha in control of breast cancer cell
      proliferation.
AB  - The 40 S ribosomal S6 kinase 1 (S6K1) acts downstream of mTOR (mammalian target
      of rapamycin) and is sensitive to inhibition by rapamycin. The chromosomal region
      17q23 containing the RPS6KB1 gene is frequently amplified in breast cancer cells,
      leading to S6K1 overexpression. The role of S6K1 in disease development and
      progression is supported by the observation that S6K1 overexpression is
      associated with poor prognosis in breast cancer patients. However, the identity
      of mammary cell-specific S6K1 targets is not well understood. In this study, we
      report that overexpression of S6K1 endows breast cancer cells with a
      proliferative advantage in low serum conditions and enhanced sensitivity to
      rapamycin. We investigate the molecular mechanism behind this observation to show
      that S6K1 regulates estrogen receptor alpha (ERalpha) by phosphorylating it on
      serine 167, leading to transcriptional activation of ERalpha. By contributing to
      the activation of ERalpha, S6K1 promotes ERalpha-mediated cell proliferation and
      may be a target of therapeutic intervention in breast cancer.

PMID- 19112173
TI  - Imaging incorporation of circulating docosahexaenoic acid into the human brain
      using positron emission tomography.
AB  - Docosahexaenoic acid (DHA; 22:6n-3) is a critical constituent of the brain, but
      its metabolism has not been measured in the human brain in vivo. In monkeys,
      using positron emission tomography (PET), we first showed that intravenously
      injected [1-(11)C]DHA mostly entered nonbrain organs, with approximately 0.5%
      entering the brain. Then, using PET and intravenous [1-(11)C]DHA in 14 healthy
      adult humans, we quantitatively imaged regional rates of incorporation (K*) of
      DHA. We also imaged regional cerebral blood flow (rCBF) using PET and intravenous
      [(15)O]water. Values of K* for DHA were higher in gray than white matter regions
      and correlated significantly with values of rCBF in 12 of 14 subjects despite
      evidence that rCBF does not directly influence K*. For the entire human brain,
      the net DHA incorporation rate J(in), the product of K*, and the unesterified
      plasma DHA concentration equaled 3.8 +/- 1.7 mg/day. This net rate is equivalent
      to the net rate of DHA consumption by brain and, considering the reported amount
      of DHA in brain, indicates that the half-life of DHA in the human brain
      approximates 2.5 years. Thus, PET with [1-(11)C]DHA can be used to quantify
      regional and global human brain DHA metabolism in relation to health and disease.

PMID- 19112175
TI  - Molecular determinants for interfacial binding and conformational change in a
      soluble diacylglycerol kinase.
AB  - DgkB is a soluble diacylglycerol (DAG) kinase that is essential for membrane
      lipid homeostasis in many Gram-positive pathogens. Anionic phospholipids, like
      phosphatidylglycerol (PtdGro), were required for DgkB to recognize diacylglycerol
      embedded in a phospholipid bilayer. An activity-independent vesicle binding assay
      was used to determine the role of specific residues in DgkB-PtdGro interactions.
      Lys15 and Lys165 were required for DgkB to dock with PtdGro vesicles and flank
      the entrance to the DgkB active site. Mg2+ was required for vesicle binding. The
      compromised vesicle binding by mutants in the key asparate residues forming the
      structural Mg2+-aspartate-water network within the substrate binding domain
      revealed that interfacial binding of DgkB required a Mg2+-dependent
      conformational change. DgkB interaction with phospholipid vesicles was not
      influenced by the presence of ATP, but anionic vesicles decreased the Km of the
      enzyme for ATP. Arg100 and Lys15 are two surface residues in the ATP binding
      domain that were necessary for high affinity ATP binding. The key residues
      responsible for the structural Mg2+ binding site, the conformational changes that
      increase ATP affinity, and interfacial recognition of anionic phospholipids were
      identical in DgkB and the mammalian diacylglycerol kinase catalytic cores. This
      sequence conservation suggests that the mammalian enzymes also require a
      structural divalent cation and surface positively charged residues to bind
      phospholipid bilayers and trigger conformational changes that accelerate
      catalysis.

PMID- 19112176
TI  - Potentiation of amyotrophic lateral sclerosis (ALS)-associated TDP-43 aggregation
      by the proteasome-targeting factor, ubiquilin 1.
AB  - TDP-43 (43-kDa TAR DNA-binding domain protein) is a major constituent of
      ubiquitin-positive cytoplasmic aggregates present in neurons of patients with
      fronto-temporal lobular dementia and amyotrophic lateral sclerosis (ALS). The
      pathologic significance of TDP-43 aggregation is not known; however, dominant
      mutations in TDP-43 cause a subset of ALS cases, suggesting that misfolding
      and/or altered trafficking of TDP-43 is relevant to the disease process. Here, we
      show that the presenilin-binding protein ubiquilin 1 (UBQLN) plays a role in TDP
      43 aggregation. TDP-43 interacted with UBQLN both in yeast and in vitro, and the
      carboxyl-terminal ubiquitin-associated domain of UBQLN was both necessary and
      sufficient for binding to polyubiquitylated forms of TDP-43. Overexpression of
      UBQLN recruited TDP-43 to detergent-resistant cytoplasmic aggregates that
      colocalized with the autophagosomal marker, LC3. UBQLN-dependent aggregation
      required the UBQLN UBA domain, was mediated by non-overlapping regions of TDP-43,
      and was abrogated by a mutation in UBQLN previously linked to Alzheimer disease.
      Four ALS-associated alleles of TDP-43 also coaggregated with UBQLN, and the
      extent of aggregation correlated with in vitro UBQLN binding affinity. Our
      findings suggest that UBQLN is a polyubiquitin-TDP-43 cochaperone that mediates
      the autophagosomal delivery and/or proteasome targeting of TDP-43 aggregates.

PMID- 19112177
TI  - Histidine triad nucleotide-binding protein 1 up-regulates cellular levels of
      p27KIP1 by targeting ScfSKP2 ubiquitin ligase and Src.
AB  - The one or more underlying mechanisms of the tumor suppressing activity of the
      histidine triad nucleotide-binding protein 1 (HINT1) are not well defined. In
      this study we found that HINT1 regulates cellular levels of the cyclin-dependent
      kinase inhibitor p27(KIP1) through multiple mechanisms. Increased expression of
      HINT1 increases cellular levels of p27(KIP1), and HINT1 knockdown with small
      hairpin RNA leads to decreased cellular levels of p27(KIP1). HINT1 does not
      affect the transcription of p27(KIP1), but it does inhibit proteasomal
      degradation of the p27(KIP1) protein. HINT1 directly interacts with the SCF(SKP2)
      ubiquitin ligase complex and inhibits the ubiquitylation of p27(KIP1). Src has
      been shown to phosphorylate p27(KIP1) and thus decrease its stability. We found
      that HINT1 is a negative regulator of Src transcription apparently by forming a
      complex with the transcription factor Sp1 on the promoter of Src. Taken together,
      our findings indicate that HINT1 up-regulates cellular levels of p27(KIP1) by two
      mechanisms: 1) it inhibits its ubiquitylation by targeting the SCF(SKP2)
      ubiquitin ligase complex, and 2) it inhibits the phosphorylation of p27(KIP1) by
      Src via inhibiting Src expression.

PMID- 19112178
TI  - A chicken ovalbumin upstream promoter transcription factor I (COUP-TFI) complex
      represses expression of the gene encoding tumor necrosis factor alpha-induced
      protein 8 (TNFAIP8).
AB  - The orphan nuclear receptor chicken ovalbumin upstream promoter transcription
      factor I (COUP-TFI) plays key roles in development and homeostasis. A tandem
      affinity purification procedure revealed that COUP-TFI associated with a number
      of transcriptional regulatory proteins in HeLa S3 cells, including the nuclear
      receptor corepressor (NCoR), TIF1beta/KAP-1, HDAC1, and the SWI/SNF family member
      Brahma. The proapoptotic protein DBC1 was also identified in COUP-TFI complexes.
      In vitro experiments revealed that COUP-TFI interacted directly with NCoR but in
      a manner different from that of other nuclear receptors. DBC1 stabilized the
      interaction between COUP-TFI and NCoR by interacting directly with both proteins.
      The gene encoding the anti-apoptotic protein TNFAIP8 (tumor necrosis factor alpha
      (TNFalpha)-induced protein 8) was identified as being repressed by COUP-TFI in a
      manner that required several of the component proteins of the COUP-TFI complex.
      Finally, our studies highlight a central role for COUP-TFI in the induction of
      the TNFAIP8 promoter by TNFalpha. Together, these studies identify a novel COUP
      TFI complex that functions as a repressor of transcription and may play a role in
      the TNFalpha signaling pathways.

PMID- 19112179
TI  - Defining developmental potency and cell lineage trajectories by expression
      profiling of differentiating mouse embryonic stem cells.
AB  - Biologists rely on morphology, function and specific markers to define the
      differentiation status of cells. Transcript profiling has expanded the repertoire
      of these markers by providing the snapshot of cellular status that reflects the
      activity of all genes. However, such data have been used only to assess relative
      similarities and differences of these cells. Here we show that principal
      component analysis of global gene expression profiles map cells in
      multidimensional transcript profile space and the positions of differentiating
      cells progress in a stepwise manner along trajectories starting from
      undifferentiated embryonic stem (ES) cells located in the apex. We present three
      'cell lineage trajectories', which represent the differentiation of ES cells into
      the first three lineages in mammalian development: primitive endoderm,
      trophoblast and primitive ectoderm/neural ectoderm. The positions of the cells
      along these trajectories seem to reflect the developmental potency of cells and
      can be used as a scale for the potential of cells. Indeed, we show that embryonic
      germ cells and induced pluripotent cells are mapped near the origin of the
      trajectories, whereas mouse embryo fibroblast and fibroblast cell lines are
      mapped near the far end of the trajectories. We suggest that this method can be
      used as the non-operational semi-quantitative definition of cell differentiation
      status and developmental potency. Furthermore, the global expression profiles of
      cell lineages provide a framework for the future study of in vitro and in vivo
      cell differentiation.

PMID- 19112180
TI  - Importance of the ionic nature of ionic liquids in affecting enzyme performance.
AB  - The activity and stability of mushroom tyrosinase were studied in ionic liquid
      (IL)-containing aqueous systems. The effect of three ILs ([BMIm][PF(6)],
      [BMIm][BF(4)]), and [BMIm][MeSO(4)], where [BMIm] = 1-butyl-3-methylimidazolium)
      and their inorganic salts (KMeSO(4), KPF(6), and NaBF(4)) on the enzyme
      performance was investigated by comparing the kinetic (such as K(m), V(max),
      optimal pH and temperature, and activation energy) and thermostability parameters
      (including half-lives, deactivation constants, activation energies for enzyme
      deactivation, DeltaG*, DeltaH*, and DeltaS*) of the enzyme in the absence and
      presence of the ILs and their anions. Both the three ILs and their inorganic
      salts were able to trigger enzyme activation. The enzyme could be stabilized by
      addition of KMeSO(4) and NaBF(4) but destabilized by the presence of all the
      three ILs. The substrate selectivity of the enzyme was unchanged. The effect of
      ILs on enzyme performance can be largely attributed to their ionic nature via
      interaction with the enzyme structure, the substrate, and the water molecules
      associated with the enzyme, depending on their kosmotropocity, nucleophilicity,
      and H-bond basicity. The different influences brought from the ILs and their
      associated ions indicate the cooperative functioning of both cation and anion of
      the IL in affecting the enzyme performance.

PMID- 19112181
TI  - Extensive antibody cross-reactivity among infectious gram-negative bacteria
      revealed by proteome microarray analysis.
AB  - Antibodies provide a sensitive indicator of proteins displayed by bacteria during
      sepsis. Because signals produced by infection are naturally amplified during the
      antibody response, host immunity can be used to identify biomarkers for proteins
      that are present at levels currently below detectable limits. We developed a
      microarray comprising approximately 70% of the 4066 proteins contained within the
      Yersinia pestis proteome to identify antibody biomarkers distinguishing plague
      from infections caused by other bacterial pathogens that may initially present
      similar clinical symptoms. We first examined rabbit antibodies produced against
      proteomes extracted from Y. pestis, Burkholderia mallei, Burkholderia cepecia,
      Burkholderia pseudomallei, Pseudomonas aeruginosa, Salmonella typhimurium,
      Shigella flexneri, and Escherichia coli, all pathogenic Gram-negative bacteria.
      These antibodies enabled detection of shared cross-reactive proteins, fingerprint
      proteins common for two or more bacteria, and signature proteins specific to each
      pathogen. Recognition by rabbit and non-human primate antibodies involved less
      than 100 of the thousands of proteins present within the Y. pestis proteome.
      Further antigen binding patterns were revealed that could distinguish plague from
      anthrax, caused by the Gram-positive bacterium Bacillus anthracis, using sera
      from acutely infected or convalescent primates. Thus, our results demonstrate
      potential biomarkers that are either specific to one strain or common to several
      species of pathogenic bacteria.

PMID- 19112185
TI  - Fifty years of world gastroenterology: the World Gastroenterology Organisation
      1958-2008.

PMID- 19112186
TI  - Do endoscopic markers still play a role in the diagnosis of celiac disease?
AB  - BACKGROUND: A number of changes in the duodenum are associated with celiac
      disease (CD), and can be identified endoscopically. Their accuracy becomes
      crucial as CD markers. This study aimed to determine the diagnostic value of
      endoscopic markers and to find ways of applying them in the diagnosis of CD.
      METHODS: Seven hundred and sixty-five consecutive patients referred for upper
      gastrointestinal endoscopy during 18 months were enrolled in the study. The
      second part of the duodenum was inspected carefully, and biopsies were taken in
      all patients to detect histologic changes suggestive of CD. RESULTS: Endoscopic
      features suggestive of CD were observed in 69 (10.6%) patients; of these, 7
      (10.1%) patients were finally diagnosed to have CD. Of the remaining 578 patients
      in whom the endoscopic markers were not seen, 2 (0.3%) patients were found to
      have CD. The overall sensitivity, specificity, PPV and NPV of the markers for the
      diagnosis of CD were 77%, 91%, 10% and 99%, respectively. Of the 9 patients who
      had CD, 5 had typical symptoms of CD and 4 had atypical features of CD.
      CONCLUSIONS: Owing to high NPV of endoscopic markers, a careful observation of
      the second part of duodenum plays an important role in the diagnosis of CD. In
      patients in whom endoscopic markers are observed, biopsies are indicated; routine
      duodenal biopsy in all patients cannot be advocated.

PMID- 19112184
TI  - Timeless Maintains Genomic Stability and Suppresses Sister Chromatid Exchange
      during Unperturbed DNA Replication.
AB  - Genome integrity is maintained during DNA replication by coordination of various
      replisome-regulated processes. Although it is known that Timeless (Tim) is a
      replisome component that participates in replication checkpoint responses to
      genotoxic stress, its importance for genome maintenance during normal DNA
      synthesis has not been reported. Here we demonstrate that Tim reduction leads to
      genomic instability during unperturbed DNA replication, culminating in increased
      chromatid breaks and translocations (triradials, quadriradials, and fusions). Tim
      deficiency led to increased H2AX phosphorylation and Rad51 and Rad52 foci
      formation selectively during DNA synthesis and caused a 3-4-fold increase in
      sister chromatid exchange. The sister chromatid exchange events stimulated by Tim
      reduction were largely mediated via a Brca2/Rad51-dependent mechanism and were
      additively increased by deletion of the Blm helicase. Therefore, Tim deficiency
      leads to an increased reliance on homologous recombination for proper
      continuation of DNA synthesis. Together, these results indicate a pivotal role
      for Tim in maintaining genome stability throughout normal DNA replication.

PMID- 19112187
TI  - The effect of dietary oils on cecal microflora in experimental colitis in mice.
AB  - OBJECTIVES: In spite of growing evidence indicating the benefits of probiotics,
      the effects of different dietary oils on intestinal microflora and probiotics
      have not been elucidated. This study aimed to examine the effects of different
      dietary oils on intestinal microflora in an experimental model of colitis.
      METHODS: Eight-week mice were fed isocaloric diets varying only in fat
      composition for 4 weeks. The oils used were fish oil, canola oil, safflower oil,
      and chow diet containing beef tallow. Colitis was induced by intracolonic
      administration of acetic acid on day 21. The inflammation and fecal microflora
      and serum lipid profiles were evaluated 1 week after induction. RESULTS:
      Inflammation was highest in the chow diet group followed by safflower, canola,
      and fish oil fed groups, respectively. The number of fecal bacteroideceae was
      greater, whereas the number of fecal bifidobacteria was lower in mice fed beef
      tallow than the other ones. In addition, fish oil reduced the plasma level of
      triacylglycerole significantly. CONCLUSION: Polyunsaturated fatty acids (PUFAs)
      can affect intestinal microflora increasing the number of probiotics. PUFAs might
      be recommended in addition to probiotics for the prevention and/or maintenance
      treatment of colitis.

PMID- 19112189
TI  - Phrygian cap in magnetic resonance cholangiogram.

PMID- 19112188
TI  - Role of IgG anti-beta-lactoglobulin antibody in the diagnosis of cow's milk
      protein intolerance in India.
AB  - OBJECTIVE: Little is known about cow's milk protein intolerance (CMPI) in India.
      This study was aimed at finding CMPI cases and determining the role of IgG anti
      beta-lactoglobulin antibody in the diagnosis of this condition in India. METHODS:
      From June 2004 to December 2005, 30 children with presumptive diagnosis of CMPI,
      based on endoscopic rectal or duodenal biopsy showing excess eosinophils and
      response to milk withdrawal, were enrolled and studied prospectively. Definite
      diagnosis was made in 20 children on the basis of positive milk challenge. IgG
      anti-beta-lactoglobulin antibodies were tested in children with CMPI before and
      after stopping milk and after milk challenge. Antibody levels were also studied
      in 27 age-matched disease controls and 50 healthy adults. RESULTS: The median age
      of 20 children (16 boys) with CMPI was 16.5 (6-36) months. Of them, 18 presented
      with diarrhea (12 bloody) and 2 had rectal bleeding. The presumptive diagnosis
      was most often (85%) based on colonic or rectal biopsy findings. Rectal biopsy
      was diagnostic in all 20 cases irrespective of the mode of presentation compared
      with duodenal biopsy which was diagnostic in 3 cases (p< 0.0001). There was no
      difference in antibody levels between cases and controls; the antibody level
      decreased significantly after milk withdrawal (p< 0.005), but did not rise
      significantly after milk re-challenge. CONCLUSIONS: CMPI is a common cause of
      chronic diarrhea in children in northern India. Sigmoidoscopy and rectal biopsy
      help in establishing the diagnosis in most cases. IgG anti-lactoglobulin antibody
      test is not useful in diagnosing CMPI in the Indian setting.

PMID- 19112190
TI  - Nutritional status of patients with Crohn's disease.
AB  - BACKGROUND AND AIM: Malnutrition is a common feature in patients with Crohn's
      disease (CD), which leads to frequent infections and poor prognosis. In view of
      the rising incidence of CD in India we planned this study to assess the
      nutritional status of patients with CD. METHODS: Nutritional status of 112
      patients (mean age 35.9 [SD 11.7] years; 61 men) with CD was assessed by
      anthropometric, dietary and biochemical parameters. Patients were considered
      malnourished if 3 or more anthropometric parameters (% ideal body weight [IBW], %
      tricep skin fold [TSF], %mid upper arm circumference [MUAC], and % mid arm muscle
      circumference [MAMC], body mass index [BMI]) were abnormal. Dietary intake was
      assessed by a 24-hour dietary recall along with a semi-quantitative food
      frequency method. Eighty volunteers were taken as healthy controls (HC). RESULTS:
      At the time of assessment, 77 patients were in remission and 35 had active
      disease. The values of BMI, MUAC, TSF and mid arm fat area (MAFA) in patients
      were significantly lower than those in healthy controls. MAMC and mid arm muscle
      area (MAMA) of patients and controls were comparable. TSF (Rem vs HC = 10.4 [2.8
      71] vs 16 [3-41]) and MAFA (Rem vs HC = 1236 [240-7757] vs 1858 [322-5650]) of
      the patients in the remission phase were significantly lower than those of
      healthy controls; the remaining parameters were comparable. There was no
      difference in the dietary intake of patients in the remission and active phases,
      and healthy controls. The percentage energy fulfillment of the patients was lower
      than that of healthy controls. Twenty-nine of 35 (82.8%) patients in the active
      and 30 of 77 (38.9%) patients in the remission phase were malnourished (OR 7.5,
      95% CI 2.8-20.4). The overall prevalence of malnutrition was 52.6% among
      patients. CONCLUSION: The percentage of malnourished patients in the active and
      remission phases of the disease was 82.8% and 38.9%, respectively, possibly due
      to low percentage energy fulfillment.

PMID- 19112191
TI  - Common NOD2 mutations are absent in patients with Crohn's disease in India.
AB  - BACKGROUND: Crohn's disease is being increasingly diagnosed in the Indian
      subcontinent. Three apparently common mutations in the NOD2 gene are found in up
      to 30% of sporadic patients with Crohn's disease in western countries. We
      examined whether such mutations are also found in Indian patients with Crohn's
      disease. METHODS: Venous blood was collected from 82 patients (age range: 7-65
      years, 53 men) with Crohn's disease and 149 control subjects; DNA was extracted
      and subjected to polymerase chain reaction using specific primers. The amplified
      fragments of size 185, 163 and 151 bp for R702W, G908R and 1007fs, respectively,
      were digested with MspI, HhaI and ApaI, and the restriction pattern noted after
      electrophoresis. RESULTS: Twenty-eight patients had ileocolonic disease, 26 ileal
      disease, 20 colonic disease and 8 had disease limited to proximal small bowel or
      stomach. None of the 82 patients showed any of the three NOD2 mutations. The
      control subjects (93 men) had a variety of chronic gastrointestinal disorders
      (ulcerative colitis 52, irritable bowel syndrome 30, intestinal tuberculosis 20,
      colon cancer 7, miscellaneous 37). None of the control subjects showed a mutation
      in any of the three NOD2 mutation analyses. CONCLUSION: The three NOD2 gene
      mutations described above are uncommon in Indian patients with Crohn's disease.
      This study complements information provided by recent studies on NOD2 mutations
      in Indians.

PMID- 19112192
TI  - Application of high-resolution narrow band imaging and endocytoscopy for early
      diagnosis of esophageal neoplasia.
AB  - The worldwide incidence of esophageal carcinoma has been rising rapidly over the
      past few decades. However, in only 31% of patients the carcinoma is detected
      early in situ. It is essential to detect the malignancy early and to determine
      the extent of the disease to ensure the best option for a cure. Recent advances
      in endoscopic technology, including high-resolution magnification endoscopy,
      narrow-band imaging and endocytoscopy, have increased detection rates of
      oesophageal microcarcinomas. We report three cases of esophageal malignancy where
      the use of newer diagnostic techniques ensured an early diagnosis which led to a
      modified course of management.

PMID- 19112194
TI  - Amyand hernia.

PMID- 19112193
TI  - Successful resolution of bronchobiliary and biliocutaneous fistula by prolonged
      endoscopic transpapillary biliary drainage.
AB  - Bronchobiliary fistula is a rare condition that has been usually treated
      surgically. We report successful resolution of a rare case of combined
      bronchobiliary and biliocutaneous fistula by prolonged endoscopic transpapillary
      biliary drainage. The patient developed these fistulae following right
      hepatectomy for blunt trauma to the abdomen. Although endoscopic biliary drainage
      has been reported to be effective in healing of post-traumatic and post-surgical
      bile leaks, there are limited reports describing the efficacy of endoscopic
      drainage in complex biliary fistulas. This case report describes the successful
      closure of complex biliary fistula by prolonged endoscopic drainage.

PMID- 19112195
TI  - Perceptions about jaundice in Assam: a preliminary study.

PMID- 19112196
TI  - Role of Gastrografin in the treatment of postoperative delayed intestinal transit
      in patients with jejunal atresia.

PMID- 19112197
TI  - Prevalence of Helicobacter pylori-associated peptic lesions among patients with
      sickle cell disease with recurrent abdominal pain.

PMID- 19112198
TI  - Hepatitis C virus co-infection among HIV-infected patients in northern India.

PMID- 19112199
TI  - Desquamative enterocolitis: an intestinal variant of Carmi syndrome presenting as
      protein-losing enteropathy.

PMID- 19112200
TI  - Integrated positron emission tomography/computed tomography fusion imaging: an
      emerging gold standard in lung cancer.
AB  - Positron emission tomography (PET) has emerged as an important diagnostic tool in
      the management of lung cancers. Although PET is sensitive in detection of lung
      cancer, but FDG (2-deoxy-2- 18 fluro-D-glucose) is not tumor specific and may
      accumulate in a variety of nonmalignant conditions occasionally giving false
      positive result. Addition of CT to PET improves specificity foremost, but also
      sensitivity in tumor imaging. Thus, PET/CT fusion images are a more accurate test
      than either of its individual components and are probably also better than side
      by-side viewing of images from both modalities. PET/CT fusion images are useful
      in differentiating between malignant and benign disease, fibrosis and recurrence,
      staging and in changing patient management to more appropriate therapy. With
      analysis and discussion it appears that PET/ CT fusion images have the potential
      to dramatically improve our ability to manage the patients with lung cancer and
      is contributing to our understanding of cancer cell biology and in development of
      new therapies.

PMID- 19112201
TI  - Newer therapeutic molecules for multiple myeloma.
AB  - Therapeutic management of multiple myeloma (MM) for the last several decades has
      mainly involved regimens based on use of glucocorticoids and cytotoxic
      chemotherapeutics. Despite progress in delineating the activity of such regimens,
      at either conventional or high doses, MM has remained an incurable disease. This
      has sparked major interest in the development of novel therapies that in part
      capitalize on recent advances in our understanding of the biology of MM,
      including the molecular mechanisms by which MM cell-host bone marrow (BM)
      interactions regulate tumor-cell growth, survival, and drug resistance in the BM
      milieu. Herein, we review the latest progress in the development of these novel
      anti-MM therapies, with major focus on therapies which have translated from
      preclinical evaluation to clinical application, including thalidomide and its
      more potent immunomodulatory derivatives (IMiD), the first-in-class proteasome
      inhibitor bortezomib (formerly known as PS-341). Search strategy included Medline
      using the terms 'Myeloma and Newer Drugs' citations relevant to treatment
      guidelines issued in 1999 and 2008 were screened.

PMID- 19112202
TI  - Awareness of breast cancer in women of an urban resettlement colony.
AB  - BACKGROUND: Breast cancer accounts for 19-34% of all cancer cases among women in
      India. There is a high mortality due to late stage diagnosis as patients usually
      present at an advanced stage because of lack of awareness and non-existent breast
      cancer screening programs. Aim : To determine the awareness about breast cancer
      among women in an urban resettlement colony in Delhi. SETTINGS AND DESIGN: A
      community based, cross-sectional study carried out in a resettlement colony in
      South Delhi. MATERIALS AND METHODS: Semi-structured interview schedule was used
      to collect information regarding breast cancer. Modified Kuppuswamy scale was
      used for assessing the socio-economic status. RESULTS AND CONCLUSIONS: A total of
      333 women were included. The mean age was 36 years+/-15.1 and 46% were
      illiterate. Only 185 (56%) women were aware of breast cancer; among them, 51%
      knew about at least one of the signs /symptoms, 53% were aware that breast cancer
      can be detected early, and only 35% mentioned about risk factors. Thus, awareness
      about breast cancer is low amongst women in this community. There is a need for
      awareness generation programs to educate women about breast cancer, propagation
      of correct messages and promote early detection of breast cancer.

PMID- 19112203
TI  - Renal function in late survivors of Iranian children with cancer: single centre
      experience.
AB  - CONTEXT: One of the side-effects of chemotherapy is nephrotoxicity, whose
      incidence rate has reportedly been higher in pediatrics. Early diagnosis of renal
      dysfunction may decrease the morbidity in those with partial or complete
      remission by avoiding nephrotoxic agents and promoting regular follow-up. AIMS:
      We studied the frequency of renal dysfunction in pediatric patients whose therapy
      was completed regardless of the type of chemotherapy. SETTINGS AND DESIGN:
      Prospective cross sectional study in Hematoncology department of children's
      hospital. MATERIALS AND METHODS: 0 One hundred and eight pediatric cancer
      patients (44 females, 64 males), who were at least one year off therapy, enrolled
      in the study from 2003 to 2005. Demographic data, mean dosages of anticancer
      drugs, history of other nephrotoxic agents, nephrectomy, radiotherapy and acute
      renal failure were recorded. Fasting blood and urine samples were collected to
      calculate fractional excretion of magnesium, calcium, phosphate, urine protein to
      urine creatinine ratio, creatinine clearance (using Schwartz formula), urine
      analysis, urine osmolality and blood gas analysis. STATISTICAL ANALYSIS USED: T
      test, Chi square and binary logistic regression were used to compare means,
      frequency and correlation respectively. P values RESULTS: Renal dysfunction was
      seen in 25.2% of cases. These abnormalities included hypercalciuria (7.2%),
      phosphaturia (13.5%), magnesuria (3.6%), glomerular filtration rate less than 90
      ml/min (7.5%), metabolic acidosis (3%), metabolic alkalosis (10%), urinary
      concentration defect (19%), proteinuria (7.2%), glycosuria (2%), microscopic
      hematuria (4%), sterile pyuria (6%), and hypertension (8%). We found only
      Procarbazin as an independent variable of nephrotoxicity (P< 0.05). CONCLUSIONS:
      Mild to moderate tubular dysfunction has been observed in the survivors of cancer
      disease.

PMID- 19112204
TI  - Is there a positive effect of participation on a clinical trial for patients with
      advanced non-small cell lung cancer?
AB  - BACKGROUND: There is general belief that patients who enrolled on a clinical
      trial have better outcomes compared to those who are treated outside of a trial.
      We analyzed if there was a 'trial effect' for patients with advanced non-small
      cell lung cancer (NSCLC) treated with chemotherapy. MATERIALS AND METHODS: A
      retrospective analysis of cohorts of patients with advanced NSCLC who received
      chemotherapy inside and outside of a clinical trial were analyzed for response
      rates (RR), progression free survival (PFS), overall survival (OS), 1 and 2 year
      survival. RESULTS: There were 194 patients who received chemotherapy of which, 54
      were on a clinical trial and 140 outside of it. For the whole group, the RR,
      median PFS, OS, one and two-year survivals were 35.4%, six months (range, 2-70),
      seven months (range, 2-72), 29.8% and 9.7% respectively. The differences in RR
      and PFS of patients who were treated inside and outside of a clinical trial were
      not significant (P=0.6164, 0.0881). The differences in median OS and one-year
      survivals between the groups were significant (P=0.0052, 0.022). For the whole
      group, patients who received II line chemotherapy had better OS (P< or = 0.0001).
      More patients in the trial group received II line chemotherapy (P=0.0004).The
      difference in the median OS between the groups continued to be significant even
      after patients who received II line chemotherapy were censored (P=0.0437).
      CONCLUSION: Patients with advanced NSCLC who were treated inside of a clinical
      trial had better OS compared to those who were treated outside of it.

PMID- 19112205
TI  - Application of computed aided detection in breast masses diagnosis.
AB  - Breast cancer is the most widespread cancer in women. The life-time risk of a
      woman developing this disease has been established as one in eight. Currently
      mammography is a standard method and could decrease breast cancer mortality.
      Unfortunately, negative mammograms don't exclude cancer. The sensitivity of
      mammography ranges from approximately 70% to 90% and it should be higher.
      MATERIALS AND METHODS: The sample contained 255 cases taken from Imaging Center
      of Imam Khomaini Hospital. Bilateral mammograms in both craniocaudal and
      mediolateral oblique projections were used. Two experienced Radiologists reviewed
      images before and after using CAD system. Tumors (including malignant and benign)
      and normal breast tissues were confirmed by histological correlation. RESULTS: Of
      255 cases 92 were not recommended for further work-up. Of 163 cases 90 were
      normal mass, 23 malignant tumors, 16 benign tumors and 22 cysts were detected by
      CAD system. The remaining cases were finalized only by biopsy. CONCLUSION: CAD
      could be utilized for breast mass detection. This is a practical technique with
      low cost.

PMID- 19112206
TI  - Evaluation of serum squamous cell carcinoma antigen as a novel biomarker for
      diagnosis of hepatocellular carcinoma in Egyptian patients.
AB  - BACKGROUND: Hepatocellular carcinoma (HCC) is the fifth most common malignancy in
      the world. In Egypt, HCC was reported to account for about 4.7% of chronic liver
      disease (CLD) patients. Squamous cell carcinoma antigen (SCCA) has been reported
      to be strongly expressed in HCC tissue hampering its extensive use in clinical
      practice. AIM: To evaluate the clinical usefulness of serum SCCA levels as a
      serological marker for early detection of HCC among high-risk patients compared
      to AFP. MATERIALS AND METHODS: The study comprised of three groups. Group A
      included 30 patients with CLD diagnosed based on clinical, laboratory, and
      ultrasonographical investigations; group B included 49 patients with HCC
      diagnostically confirmed by spiral CT, elevated alfafetoprotein (AFP), and/or
      liver biopsy; and group C, the control group, included 15 healthy subjects
      matched for age and sex. All groups were subjected to thorough history taking,
      full clinical examination, and laboratory investigations including liver
      functions, viral markers, and AFP and SCCA estimation using ELISA technique.
      RESULTS: This study revealed a highly significant difference between patients
      with HCC, CLD, and controls regarding serum SCCA levels (5.138 +/- 7.689, 1.133
      +/- 0.516, and 0.787 +/- 0.432 ng/ml, respectively). SCCA level was persistently
      elevated in patients with HCC with normal AFP levels representing its useful role
      in early detection and follow-up of patients treated for HCC. The area under the
      curve (AUC) of SCCA was 0.869 (95% CI 0.783-0.929), the cut-off value was
      established at 1.5 ng/ml with sensitivity of 77.6% and specificity of 84.4%). The
      difference between AUC of SCCA and that of AFP was 0.09 which mounted statistical
      significance. CONCLUSIONS: SCCA could represent a useful tool as a marker for
      detection of HCC.

PMID- 19112207
TI  - Leiomyoma of the nasal septum.
AB  - Leiomyoma of nasal cavity is an extremely rare and unusual benign mass that
      uncommonly arises from the nasal septum. These are vascular or nonvascular masses
      of myogenic origin. We present a rare case of leiomyoma arising from the nasal
      septum and discuss its management using KTP 532 laser.

PMID- 19112208
TI  - Ductal adenocarcinoma of ventral surface of the tongue: an unusual presentation.
AB  - There are very few cases reported of adenocarcinoma of the tongue. We report an
      unusual case of a 60-year-old female having a large, pedunculated ductal
      adenocarcinoma that had arisen from ventral surface of the tongue. The lesion was
      managed by surgery.

PMID- 19112209
TI  - Adenocarcinoma at angle of treitz: a report of two cases with review of
      literature.
AB  - We report two patients with adenocarcinoma at angle of treitz who presented with
      upper GI(gastrointestinal) obstruction and underwent segmental resection of
      duodeno-jejunal junction. Preoperative investigations failed to reveal the nature
      of the lesion suggesting the elusive nature of these lesions, importance of
      clinical suspicion and decision-making.

PMID- 19112210
TI  - Ipsilateral axillary tubercular lymphadenopathy, contralateral osseous
      tuberculosis in a case of ductal carcinoma of breast.

PMID- 19112211
TI  - Defining age cut off age for "Young patients" with breast cancer.

PMID- 19112212
TI  - Transitional cell cancer of ureter misdiagnosed as pelviureteric junction
      obstruction: pitfalls of standard diagnostic tools.

PMID- 19112213
TI  - Short daily and nocturnal hemodialysis: new therapies for a new century?
AB  - The National Institutes of Health (NIH) sponsored HEMO Study did not demonstrate
      that an increase in dialysis dose was associated with an improvement in patient
      mortality rates. Despite this negative result, there is ongoing interest in
      determining if still higher doses of dialysis may be of benefit to patients
      receiving chronic hemodialysis therapy. Testing this hypothesis requires the use
      of more fre-quent hemodialysis and/or a much longer duration for each dialysis
      session. "Short daily hemodialysis", actually six times per week hemodialysis for
      1.5 to 3 hours per session, provides a significant increase in small molecule
      clearance as measured by urea kinetics. "Long nocturnal daily hemodialysis",
      actually six times per week hemodialysis for 6-8 hours per session, provides a
      significant increase in both small and large molecular weight clearance and often
      alleviates the need to take phosphate binders. Both forms of more frequent
      dialysis have been shown to improve control of blood pressure. One small
      randomized trial of nocturnal versus conventional home dialysis showed a decrease
      in left ventricular (LV) mass at 6 months in the nocturnal arm only. Most
      clinical trials conducted in these dialysis modalities have been observational
      trials and have enrolled small numbers of patients. The National Institutes of
      Health is sponsoring two clinical trials via the Frequent Hemodialysis Network to
      determine the effect of these two more frequent dialysis modalities on
      intermediate outcomes. In the short daily study, 250 patients will be randomized
      to receive either six times per week HD, with a session length of 1.5 to 2.75
      hours, or conventional in-center hemodialysis. In the nocturnal study, 150
      patients will be randomized to receive either six times per week overnight
      dialysis, with a session length of at least 6 hours, or conventional home
      hemodialysis.

PMID- 19112214
TI  - Role of bone biopsy in renal osteodystrophy.
AB  - Renal osteodystrophy (ROD), the abnormal bone histology that occurs in the
      context of kidney disease, is a disease spectrum and not a uniform progressive
      bone disease. It is an important component of the broad disturbances of bone and
      mineral metabolism associated with chronic kidney disease (CKD). There are
      multiple pathogenetic factors which contribute to the histological abnormalities
      seen on bone biopsy. The patients with ROD are rarely symp-tomatic in the early
      stages of CKD. It is also noteworthy that the clinical manifestations are usually
      preceded by biochemical changes that are insidious and subtle. This makes it
      difficult for the clinician to suspect the presence of bone and mineral
      metabolism abnormalities without direct testing. The serum calcium, phosphorus,
      and alkaline phosphatase levels are usually normal until late in the course of
      CKD. The main screening test for abnormal bone and mineral metabolism is the
      measurement of parathyroid hormone which is also somewhat delayed. The clinical
      signs and symptoms are also challenging to interpret because of their slow and
      non-specific nature which may include vague, ill-defined, bone aches and pains,
      and muscle weakness. The gold standard for diagnosis of ROD is bone biopsy with
      mineralized bone histology after double tetracycline labeling, iron staining and
      aluminum staining. The currently used histomorphometric descriptions of bone
      histology are not well integrated clinically and a new nomenclature that is
      clinically more relevant and useful has been proposed. Additional studies are
      required to define the spectrum of ROD in the current therapeutic era, and to
      find clinically useful non-invasive biomarkers to improve the treatment and
      monitoring of the abnormal bone in the setting of CKD.

PMID- 19112215
TI  - Oral lesions in Saudi renal transplant patients.
AB  - Renal transplantation has evolved as the best treatment option for patients with
      end-stage renal disease. Different oral problems arise in these patients, either
      as a direct consequence of drug-induced immunosuppression or pharmacokinetics. To
      determine the prevalence of intra-oral lesions in a group of medically stable
      Saudi renal transplant patients (RTP) and to identify possible risk factors, in
      comparison with age and sex-matched healthy control subjects (HCS), we studied 58
      RTP and 52 HCS. All subjects had a thorough oral examination and oral lesions
      were diagnosed according to the clinically accepted criteria. Gingival overgrowth
      (GO), erythematous candidiasis (EC) and hairy leukoplakia (HL) were diagnosed in
      RTP with prevalence of 74.1%, 15.5%, and 8.6%, respectively. The severity of the
      gingival overgrowth significantly correlated with the use of cyclosporine and
      nifedipine combination therapy, serum cyclosporine, and serum creatinine level.
      In conclusions, the finding of our study strongly propose that RTP should undergo
      routine and regular comprehensive oral examination, and any suspicious lesion
      must be investigate and treated.

PMID- 19112216
TI  - Burden among care-givers of kidney transplant recipients and its associated
      factors.
AB  - Burden among care-givers of chronically ill patients has been widely
      investigated. However, there is no study evaluating perceived pressure on care
      givers of kidney transplant recipients. This study aimed to evaluate the effect
      of care-giving to renal transplant recipients in Iranian Muslim population and to
      analyze factors associated with it. A cross-sectional study was carried out
      involving 41 care-givers of renal recipients. The Care-giver Burden Scale (CB
      Scale) was used to evaluate the care-giver's perceived burden and its correlates.
      Statistical analysis was performed using software SPSS v.13.0. P (p 0.05), and
      being a parent or spouse to the patient (p 0.05). We also found significant
      adverse effects of patients' second transplantation and gender (male) on care
      givers' burden. There was no significant relationship between care-giver burden
      score and patients' marital status, education level, operation time, age, donor
      type (cadaveric or living), and dialysis history before and after
      transplantation. In conclusion, care-givers experience strain, which has
      implications for research and service provision. Service providers need to
      identify those care-givers at risk of greater strain and help them in situations
      that cannot be altered. Future research should be conducted to identify the
      effects of interventions, on care-givers' burden perception.

PMID- 19112217
TI  - Value of color Doppler sonography in the assessment of hemodialysis access
      dysfunction.
AB  - Arteriovenous fistula (AVF) is the most widely used means of vascular access for
      long-term hemodialysis (HD) and the complication rate related to AVF remains
      high. This study was conducted to determine the efficiency of Color Doppler
      sonography (CDS) in the assessment of AVF dysfunction. Over a period of 29
      months, from January 2005 to May 2007, a total of 55 patients with AVF access
      dysfunction were included in the study. CDS were performed in the King Fahd
      Hospital of the University, Al-Khobar, Saudi Arabia. CDS allowed identification
      of 23 patients with stenotic segments and 16 others with venous thromboses. Six
      patients with venous aneurysm were encountered. Doppler flow rate assessment
      allowed differentiation of venous hypertension in two patients and steal syndrome
      in two other patients. Thus, the CDS findings carried a sensitivity rate of
      96.4%. Two subclavian vein stenoses, causing reduced blood flow rate, were missed
      by CDS and later confirmed by angiography. Thirty-four patients underwent
      operative intervention. Our study suggests that CDS is an ideal noninvasive
      technique that allows the assessment of both anatomy and hemodynamics of an AVF.

PMID- 19112218
TI  - Non-cuffed dual lumen catheters in the external jugular veins versus other
      central veins for hemodialysis patients.
AB  - To compare prospective between insertion of non-cuffed dual lumen catheter in the
      external jugular vein and other central veins for hemodialysis (HD), we studied
      68 chronic dialysis patients randomly allocated into two groups: one with
      external jugular vein catheterization as access for HD and another with other
      central venous catheterization, internal jugular or subclavian vein. Our results
      showed there were no significant differences regarding successful cannulation,
      com-plications, total numbers of dialysis, development of pain and infection at
      the site of cannulation, patency rate of the catheters, and efficacy of
      hemodialysis between both groups. In addition, the patency of the catheter in the
      external jugular vein was not affected by previous cannulation of other central
      veins. In contrast, there was a significant correlation between numbers of
      attempts for cannulation in both groups and development of hematoma and
      infection, (p< 0.05). In conclusion, our results showed that the external jugular
      vein may be an alternative for other central veins for insertion of temporary non
      cuffed hemodialysis catheter.

PMID- 19112219
TI  - The influence of maintenance quality of hemodialysis machines on hemodialysis
      efficiency.
AB  - Several studies suggest that there is a correlation between dose of dialysis and
      machine maintenance. However, in spite of the current practice, there are
      conflicting reports regarding the relationship between dose of dialysis or
      patient outcome, and machine maintenance. In order to evaluate the impact of
      hemodialysis machine maintenance on dialysis adequacy Kt/V and session
      performance, data were processed on 134 patients on 3-times-per-week dialysis
      regimens by dividing the patients into four groups and also dividing the
      hemodialysis machines into four groups according to their year of installation.
      The equilibrated dialysis dose eq Kt/V, urea reduction ratio (URR) and the
      overall equipment effectiveness (OEE) were calculated in each group to show the
      effect hemodialysis machine efficiency on the overall session performance. The
      average working time per machine per month was 270 hours. The cumulative number
      of hours according to the year of installation was: 26,122 hours for machines
      installed in 1998; 21,596 hours for machines installed in 1999, 8362 hours for
      those installed in 2003 and 2486 hours for those installed in 2005. The mean time
      between failures (MTBF) was 1.8, 2.1, 4.2 and 6 months between failures for
      machines installed in 1999, 1998, 2003 and 2005, respectively. Statistical
      analysis demonstrated that the dialysis dose eq Kt/V and URR were increased as
      the overall equipment effectiveness (OEE) increases with regular maintenance
      procedures. Maintenance has become one of the most expedient approaches to
      guarantee high machine dependability. The efficiency of dialysis machine is
      relevant in assuring a proper dialysis adequacy.

PMID- 19112220
TI  - Evaluating kidney damage from vesico-ureteral reflux in children.
AB  - To review the most relevant clinical studies that evaluate kidney damage in
      children with primary vesico-ureteral reflux (VUR), we reviewed and compared
      randomized controlled trials and clinical trials from scientific literature. In
      these studies, vesico-ureteral reflux was diagnosed by voiding cystourethrogram
      and kidney damage was assessed by either DMSA scan or urography. Relative risk
      with 95% confidence intervals was calculated using Review Manager Software (The
      Cochrane Collaboration, 2000). The overall relative risk of kidney damage shown
      by DMSA scan and urography was statistically higher in children with vesico
      ureteral reflux of various degrees than in controls (3.7 times and 2.8 times,
      respectively). However, in high-grade VUR, the relative risk of congenital kidney
      damage was 5.6 times that of controls. We conclude that severe VUR is frequently
      associated with early kidney damage, perhaps with prenatal onset. Progression of
      kidney damage may depend on the severity of VUR and untreated urinary tract
      infections. Prevention of congenital kidney damage from severe VUR is possible
      when there is early intervention, even during fetal growth.

PMID- 19112221
TI  - Acute renal failure in pediatric patients: etiology and predictors of outcome.
AB  - Acute renal failure (ARF) is the acute loss of kidney function over hours or
      days, the etiology of which varies in different countries. The data on the
      etiology and outcome of ARF in Arab children is limited. Our objective was to
      define the causes and predictors of outcome of ARF in Kuwaiti children, and the
      variables determining their fitness for dialysis. A total of 32 children with ARF
      were evaluated regarding their demographic and clinical data, the cause of ARF
      and the co-morbidities. Data were analyzed to find the independent variables
      determining fitness for dia-lysis and outcome. Males comprised 62.5% of the study
      children; 46.9% of ARF cases were due to sepsis and 56.2% underwent renal
      replacement therapy (RRT). Univariate analysis showed that age, hemodynamic
      instability, use of vasopressors, multi-organ failure (MOF), and mechanical venti
      lation contributed to fitness for dialysis. However, MOF was the only independent
      variable affecting fitness for dialysis. The overall mortality was 43.8%.
      Univariate analysis showed that age below 24-months, hemodynamic instability, use
      of vasopressors, fluid overload, need for mecha-nical ventilation, MOF and late
      referral to the nephrologist were associated with poor outcome. However,
      multivariate analysis documented MOF, and the time of nephrologists' intervention
      as independent prognostic indicators. Our study suggests that sepsis was the
      major cause of pediatric ARF. RRT is the optimal treatment, and the only factor
      determining child's fitness for dialysis is MOF.

PMID- 19112222
TI  - Microvascular and macrovascular complications in diabetic nephropathy patients
      referred to nephrology clinic.
AB  - To evaluate the diabetic complications and fate of diabetic nephropathy in Saudi
      population, we studied 184 diabetic nephropathy (DN) patients who were referred
      to nephrology clinic of King Khalid University Hospital, Riyadh, Saudi Arabia
      from January 2003-June 2006. The patients had mean age of 61.9 +/- 13.1 years,
      included 128 (69.6%) males, and were followed up for a mean period of 10.2 +/-
      1.5 years. The mean duration of diabetes mellitus (DM) was 19.5 +/- 5.8 years,
      and duration of nephropathy was 7.7 +/- 3.3 years. Family history of DN was
      documented in 52 (28.2%) patients. At initial visit, the mean systolic blood
      pressure was 164 +/- 14.5 mmHg, the mean diastolic blood pressure was 97.9 +/-
      10.4 mmHg. Thirty-seven (20%) patients had normal BMI, 88 (48%) were overweight,
      while 55 (30%) were obese. Mean creatinine clearance was 51.7 +/- 26.3 mL/min, 24
      hrs urinary proteins 1.99 +/- 2.48 gm/day, HbA1C 9.2 +/- 1.8 %, triglyceride 2.1
      +/- 1.3 mmol/L, and cholesterol 5.17 +/- 1.54 mmol/L. Diabetic complications
      included angiography proven coronary artery disease in 106 (57.6 %) patients,
      stroke in 21 (11.4%), myocardial infarction (MI) in 27(14.6%), angina in 87 (47.2
      %), retinopathy in 82 (44.5%), Blindness in 3 (1.6%), peripheral vascular disease
      in 121 (65.7%), Neuropathy in 123 (66.8%), hypertension in178 (96.7%), diabetic
      foot in 25 (13.5%), Amputation in 10 (5.4%), and end-stage renal disease in 70
      (38%). Total of 13 (7.05%) patients died in the hospital. Thirty-seven percent of
      patients developed > 6 concomitant complications. 28% developed 5, 17% developed
      4, and the rest developed < 3. DN was relatively refractory to therapy and
      progressive; 123 (66.8%) patients doubled their serum creatinine in 3.59 +/- 2.88
      years, 32 (17.3%) maintained stable renal function, 136 (73.6 %) deteriorated,
      and 12 (6.52%) improved. we conclude that the prevalence of diabetic
      complications is high among Saudi patients, and many had multiple complications.
      Baseline creatinine clearance and proteinuria, high systolic blood pressure,
      advanced age, and longer duration of diabetes were the most significant risk
      factors for developing complications.

PMID- 19112223
TI  - Utility of predicted creatinine clearance using MDRD formula compared with other
      predictive formulas in Nigerian patients.
AB  - The new predictive formula generated during the study of Modification of Diet in
      Renal Disease (MDRD) to estimate the glomerular filtration rate in chronic kidney
      disease (CKD) patients was found to be superior to existing predictive formulas
      in all races including black Americans. We had previously published a study
      evaluating and comparing 5 predictive formulas and their applicability in
      Nigerian CKD patients and normal subjects. The existing data from this study were
      re-analyzed and the 5 previous formulas compared with the MDRD formula. All the
      predictive formulas including the MDRD formula correlated significantly with
      measured creatinine clearance in CKD subjects and controls. Correlation
      Coefficient, (r) ranged between 0.908-0.968 and Coefficient of Determination, (r
      2 ), ranged between 0.826-0.936. There was also good correlation between the
      measured and predicted CrCl in healthy state, though the r and r 2 values were
      weaker (0.718-0.957) and (0.516-0.916). Specifically, MDRD formula was only
      superior to Jelliffe and Gates and not so to Cockcroft and Gault, Hull, and Mawer
      equations in CRF. MDRD formula yielded r= 0.93 and r 2 = 0.86 and the values for
      Cockcroft and Gault, Hull and Mawer ranged between 0.96-0.97 and 0.93-0.94
      respectively. In conclusion, MDRD formula, though useful and applicable was not
      superior to existing formulas. Cockcroft and Gault equation can still be used due
      to the ease of recall and its high correlation coefficient in health and disease
      states.

PMID- 19112224
TI  - Assessment of the effect of radio contrast media on resistive index of renal
      artery by color doppler sonography.
AB  - Renal ischemia and direct toxic effect of contrast media are the main confounding
      causes of contrast-induced nephropathy (CIN). The effect of different contrast
      mediums on the resistance of renal artery is quite unclear. The aim of the
      present study was to assess the resistive index (RI) changes of renal segmental
      artery in color Doppler duplex sonography after injection of two different
      contrast mediums: iodixanol and iohexol. The RI of the renal segmental artery of
      62 randomly chosen patients, with a normal baseline renal function, was
      calculated using color-coded Doppler sonography before and five minutes after
      bolus injection of two different contrast mediums. Thirty-one patients were
      administered 50 mL of iodixanol (Visipaque) and 31 patients were administered 50
      mL of iohexol (Omnipaque) during intravenous urogram procedures. The RI results
      were analyzed and compared in two groups using two-tailed t-test. The mean RI of
      renal segmental artery increased significantly after administration of contrast
      media (mean +/- SD 0.61 +/- 0.046 vs 0.58 +/- 0.042; p< 0.001). The mean change
      of RI was 0.0387 +/- .00552 (mean +/- SE) in the setting of iohexol injection and
      0.0216 +/- .00423 (mean +/- SE) five minutes after administration of iodixanol
      (p= 0.017). Both non-ionic iso-osmolar dimeric iodixanol and low-osmolar iohexol
      increase the renal artery resistance, but the changes are more dramatic with
      iohexol, suggesting better tolerance with iodixanol.

PMID- 19112225
TI  - HLA class I and II antigens expression in patients with renal cell carcinoma.
AB  - An optimal antitumoral immune response requires the activation of both CD8(+) and
      CD4(+) T lymphocytes by the peptide antigen presentation via the human leukocyte
      antigen (HLA) class I and class II molecules, respectively. The frequency of A1,
      A26, DR11 alleles are significantly elevated and seem to be the predisposing
      alleles in RCC, while HLA A29 and DQ1 are the protective alleles and are found
      more frequently in the healthy group. To investigate the association between
      renal cell carcinoma (RCC) and the host's immune system, we immunohistochemically
      examined RCCs in 44 Turkish patients for the expression of class I and class II
      antigens. We found a significantly higher frequency of the alleles HLA-A1 (p=
      0.001), HLA-A26 (p=0.047) and HLA-DR11 (p= 0.03) in RCC patients compared to the
      control group. The most frequent alleles in the control population were A29, DQ1
      (p= 0.004 and 0.002 respectively). We observed no significant difference between
      patients and controls in HLA-B and HLA-C allele frequency. We conclude that our
      study found an association between HLA antigens and RCC in Turkish patients. We
      found a significantly higher frequency of the alleles HLA-A1, HLA-A26 and HLA
      DR11in RCC patients compared to the control group. Larger studies are required to
      confirm these results.

PMID- 19112226
TI  - Renal involvement in children with spina bifida.
AB  - Renal scarring and renal failure remain life-threatening for children born with
      spinal dysraphism. An early start of therapy helps to safeguard renal function
      for such children and avoid end-stage renal disease. However, optimal care is not
      always available in developing countries. We reviewed our data on all newborns
      with spina bifida who were born at King Abdulaziz University Hospital between
      1997 and 2006. Thirty-three children with myelomeningocele (MMC) were evaluated;
      MMC site was thoracolumbar in 26 patients (77.1%) and in the lumbosacral area in
      7 patients (22.9%). The mean age at the time of evaluation was 5.4 +/- 2.3 years.
      Thirty (90%) patients presented with neurogenic bladder, and 26(78%) with vesico
      uretral reflux (VUR). Only 8 patients (group A) received clean intermittent
      catheterization (CIC), while the rest (group B) were either non-complaint or not
      on any therapy. Urinary tract infections overall were 4.5 +/- 3.8 per year.
      Patient undergoing CIC had a lower number of UTI (mean per year) 3.3 +/- 1.2 vs
      6.6 +/- 2.3. Sixty two percent of group A had VUR compared with 93% in group B.
      The mean creatinine was 46 +/- 39 micromol/L for the whole group. However, group
      A had a lower mean creatinine 38 +/- 11 compared to 50 +/- 34 in group B. In
      conclusion, early intervention to relieve urinary retention in children born with
      spina bifida resulted in preserving renal function and less incidence of VUR and
      UTI. There is a need of more awareness about the importance of starting proactive
      treatment of risks of upper urinary tract disease and development of renal
      failure in babies with spina bifida.

PMID- 19112228
TI  - Early post transplantation renal allograft perfusion failure due to intimal
      dissection of the renal artery.
AB  - Transplant renal artery stenosis (TRAS) is a recognized and potentially curable
      cause of post transplant arterial hypertension, allograft dysfunction, and graft
      loss. It usually occurs 3 months to 2 years after transplantation, but early or
      later presentations are not uncommon. We present a case of renal artery narrowing
      due to intimal dissection that was managed medically.

PMID- 19112227
TI  - Selenium intoxication with selenite broth resulting in acute renal failure and
      severe gastritis.
AB  - Selenium (Se) is an essential trace element in human and animal nutrition. It is
      also widely utilized in industrial processes. Reports of acute selenium toxicity
      in humans are rare. We report a case of a 23-year-old female who consumed about
      100 mL of liquid selenite broth and presented with severe nausea, vomiting,
      abdominal pain, hematemesis and acute renal failure (ARF). The serum selenium
      level was significantly increased. Gastro-duodenoscopy revealed severe corrosive
      gastritis. Renal biopsy showed features of acute tubular necrosis (ATN),
      affecting primarily the proximal tubules. The patient was managed with gastric
      lavage, blood transfusions, infusion of fresh frozen plasma (FFP) and platelet
      concentrates and hemo-dialysis. The patient was discharged five weeks after
      admission and her renal functions recovered completely by eight weeks after
      admission. She continues to be on regular follow-up for any possible sequelae of
      mucosal corrosive damage. This case highlights a case of selenium intoxication
      from selenite broth resulting in ARF and corrosive gastritis. The recovery was
      complete.

PMID- 19112229
TI  - Minimal change disease versus IgA nephropathy.
AB  - IgA nephropathy is the most common type of the glomerulonephritis all over the
      world. However, its clinical presentation is variable, as is the underlying
      histopathological lesion. We report herein a case of an adult with steroid
      responsive minimal change disease and IgA mesangial deposits. During the first
      two weeks of therapy with prednisolone, the patient reported dramatic improvement
      in his clinical condition and remitted his disease. Unfortunately, at the end of
      the second month of prednisolone therapy, an acute flare of viral hepatitis was
      diagnosed. Interes-tingly, the acute viral flare was without a concomitant
      relapse of proteinuria.

PMID- 19112230
TI  - Reflex anuria affecting both kidneys following hysterectomy.
AB  - In situations when there is unilateral ureteral obstruction, the contralateral
      kidney retains its normal function. In rare instances however, it has been
      reported that unilateral ureteral obstruction can lead to reflex anuria (RA) and
      acute renal failure (ARF). Even more unusually, RA with ARF can occur without
      organic obstruction due to ureteric manipulation during pelvic surgery. We report
      a 78- year-old woman, who underwent hysterectomy because of endometrial
      carcinoma. She developed ARF evidenced by anuria of 120-hours duration, and
      gradual rise of serum creatinine levels to 11.8 mg/dL on the fifth day after
      hysterectomy. Ultrasound study of the urinary tract revealed bilateral moderate
      hydronephrosis. Detailed evaluation did not reveal any organic obstruction. She
      was managed with hemodialysis, control of hypertension and correction of fluid
      and electrolyte imbalances. By the sixth day, diuresis was established, and the
      blood urea and serum creatinine levels decreased to normal by the sixteenth day.
      The patient was finally discharged on the eighteenth day. Our case suggests that
      urologists and nephrologists should consider RA as one of the causes of anuria
      and ARF.

PMID- 19112231
TI  - Renal cell carcinoma in a child.
AB  - Renal cell carcinoma is a rare disease in children and adolescent. Less than 2%
      of cases occur in childhood and no treatment protocols exist among urologists and
      oncologists for management. We present a case of renal cell carcinoma in a child
      with uncommon presentation.

PMID- 19112232
TI  - Severe rhabdomyolysis and acute renal failure secondary to use of simvastatin in
      undiagnosed hypothyroidism.
AB  - A 52-year-old Indian woman with underlying diabetes mellitus and hyperlipidemia,
      presented with generalized musculoskeletal pain and oliguria for three days. The
      patient was taking 80 mg of simvastatin initiated 20 days earlier after cardiac
      catheterization for an inferior myocardial infarction. Laboratory investigations
      revealed the following serum levels: creatine kinase 81,620 U/L, aspartate
      aminotransferase 2497 U/L, alanine aminotransferase 1304 U/L, blood urea nitrogen
      21.7 mmol/L, creatinine 447 micromol/L, Free T4 12.6 pmol/L, and thyroid
      stimulating hormone (TSH) 22.7 microIU/L. Simvastatin was discontinued and the
      patient received forced alkaline diuresis. Her hypothyroidism was treated with
      thyroxin, which was continued upon discharge, and her renal function recovered
      within two months. This case report discusses the incidence of rhabdomyolysis in
      a patient with primary hypothyroidism receiving large doses of simvastatin.

PMID- 19112233
TI  - Continuous ambulatory peritoneal dialysis in a patient with scleroderma.

PMID- 19112234
TI  - Granulomatous interstitial nephritis after prolonged use of phenytoin.

PMID- 19112235
TI  - Pulmonary aspergilloma in a patient on hemodialysis.

PMID- 19112236
TI  - Empirical treatment for pediatric urinary tract infection and resistance patterns
      of uropathogens, in Queen Alia hospital and prince A'Isha military center-
      Jordan.
AB  - We conducted this retrospective study to identify the most appropriate oral
      antibiotic as empiric treatment of urinary tract infection according to
      resistance patterns of uropathogens among children treated at Queen Alia Military
      Hospital and Prince Aisha Bent Al-Hussein Military Center from January 2006 to
      April 2007. Urine cultures for isolated microorganism and their anti-biotic
      susceptibility in patients below the age of 14 years treated as outpatient were
      reviewed. Out of 3820 cultures, 529 isolates were found, E coli was the most
      frequent organism. Resistance to Ampicillin, sulfamethoxazole, and trimethoprim
      (TMP-SMZ) was common, and multidrug-resistant (MDR) among E. coli isolates was
      59.9%. Knowledge of patterns of resistance at each institution helps in deciding
      empiric therapy for UTI. Pretreatment urine culture should be performed and
      followed up for the continuation of the treatment.

PMID- 19112237
TI  - Epidemiology of hemodialysis patients in Aleppo city.
AB  - To determine the characteristics of the hemodialysis (HD) patients in Aleppo
      city, we surveyed the hospitals representing the main dialysis centers in the
      city including private and community facilities during 2006. Personal patients'
      interviews and hospitals records were the source of data. The total number of
      patients in 2006 undergoing HD was 550 patients; 280 (50.9%) were males, and the
      age ranged from 5-82 years with mean and median age 44.7 and 45 years,
      respectively. The incidence (IR) and prevalence rate (PR) for hemodialysis were
      60 pmp and 226 pmp, respectively. The major primary renal diseases in the end
      stage renal disease (ESRD) patients included hypertension (HTN),
      glomerulonephritis (GN), and diabetes mellitus (DM), 21.1%, 20.5 %, and 19.45,
      respectively. The percent of Anti-HCV, HBV hepatitis and HBV vaccine were 54.4%,
      7.8%, and 52.9%, respectively. This study suggests that the IR of hemodialysis
      was relatively low due to the high cost of treatment, and the PR for hemodialysis
      was also relatively low may be due to high mortality rate and low kidney
      transplantation rate in this country. There was an equal percentage of both
      genders in the hemodialysis population.

PMID- 19112238
TI  - Hepatitis C virus infection among patients on hemodialysis: a report from a
      single center in Iran.
AB  - The aim of this study is to evaluate the incidence of hepatitis C virus (HCV)
      infec-tion among the hemodialysis (HD) patients at the Nephrology and Urology
      Research Center, Tehran, Iran, and identify the potential risk factors. A total
      of 112 patients on HD in our two dia-lysis units were studied. The mean duration
      of follow-up was 27 +/- 27 months (range, 6-132). All study subjects were HCV
      negative at entry to the study and were tested for anti-HCV antibody by ELISA II
      every six months thereafter. Positive samples were re-examined by RT/PCR for
      confir-mation. Factors that might be implicated in HCV transmission were
      evaluated. Six patients (5.3%) were labeled as HCV infected, at the end of the
      follow-up period. Thus, the incidence of HCV infection in our dialysis units was
      1.8 per 100 person years. A total of 64.5% of the study popu-lation had previous
      history of blood transfusion(s) and 8% had undergone prior transplantation.
      Univariate analysis showed a significant relationship between number of blood
      transfusions and duration on dialysis and HCV infection. Multivariate analysis
      revealed that only duration on HD was significantly associated with HCV
      positivity (OR: 1.03, p=0.008). Our study further suggests that nosocomial
      transmission plays a major role in HCV transmission among patients on HD.
      Meticulous practice of preventive measures is essential to eradicate the spread
      of HCV in HD units.

PMID- 19112239
TI  - The Islamic perspective of organ donation in Pakistan.

PMID- 19112240
TI  - Blinded by degrees.

PMID- 19112241
TI  - What were they thinking?

PMID- 19112242
TI  - Acknowledging APRNs.

PMID- 19112243
TI  - Still holding the thread.

PMID- 19112244
TI  - Still holding the thread.

PMID- 19112245
TI  - Environmental health.

PMID- 19112248
TI  - The top health care news story of 2008: the ailing economy.

PMID- 19112249
TI  - The top nursing story of 2008: Why can't nurses just get along?

PMID- 19112257
TI  - The initiative to create a national nurse: stalled.

PMID- 19112258
TI  - Australia gets chief nursing and midwifery officer.

PMID- 19112259
TI  - Staging pressure ulcers: what's the buzz in wound care?

PMID- 19112263
TI  - Nurses and the pharmaceutical industry: part 1.

PMID- 19112266
TI  - Contrasts in long-term care.

PMID- 19112264
TI  - Case study: dying with a stage IV pressure ulcer.

PMID- 19112267
TI  - Bullying among nurses.

PMID- 19112271
TI  - One-hour, off-unit meal breaks.
AB  - This is the fifth in a series of articles from Massachusetts General Hospital in
      Boston describing one general medical unit's experiences with Transforming Care
      at the Bedside (TCAB). An initiative begun by the Robert Wood Johnson Foundation
      (RWJF) and the Institute for Healthcare Improvement, TCAB was developed as a way
      to improve care on medical-surgical units, patients' and family members'
      experience of care, and teamwork among care team members, and to increase
      satisfaction and retention of nurses. The TCAB philosophy engages all care
      leaders but empowers bedside nurses to generate ideas and solutions for change.
      Mass General is one of 68 hospitals participating in a two-year TCAB initiative
      led by the American Organization of Nurse Executives and funded by a grant from
      the RWJF. For more information on TCAB, go to
      www.rwjf.org/pr/product.jsp?id=31512.

PMID- 19112274
TI  - Monitoring medication use in older adults.
AB  - The Beers Criteria for Potentially Inappropriate Medication Use in Older Adults
      assessment instrument highlights specific medications whose risks to older adults
      may outweigh their benefits. Nurses can use the criteria to evaluate medications
      for risks that warrant follow-up with older adults in various settings, including
      hospitals, nursing homes, and private homes. Watch a video demonstrating the use
      of the Beers criteria at http://links.lww.com/A266.

PMID- 19112269
TI  - Solving the puzzle of prematurity.

PMID- 19112276
TI  - The new administration and health care reform.

PMID- 19112277
TI  - Sibling advocacy.
AB  - That course in nursing ethics may be more useful than you think.

PMID- 19112278
TI  - Sodium bicarbonate to prevent increases in serum creatinine after cardiac
      surgery: a pilot double-blind, randomized controlled trial.
AB  - OBJECTIVE: To test whether perioperative sodium bicarbonate infusion can
      attenuate postoperative increases in serum creatinine in cardiac surgical
      patients. DESIGN: Double-blind, randomized controlled trial. SETTING: Operating
      rooms and intensive care unit at a tertiary hospital. PATIENTS: Cohort of 100
      cardiac surgical patients at increased risk of postoperative acute renal
      dysfunction. INTERVENTION: Patients were randomized to either 24 hrs of
      intravenous infusion of sodium bicarbonate (4 mmol/kg) or sodium chloride (4
      mmol/kg). MEASUREMENTS AND MAIN RESULTS: The primary outcome measure was the
      proportion of patients developing acute renal dysfunction defined as a
      postoperative increase in plasma creatinine concentration >25% of baseline within
      the first five postoperative days. Secondary outcomes included changes in plasma
      creatinine, plasma urea, urinary neutrophil gelatinase-associated lipocalin, and
      urinary neutrophil gelatinase-associated lipocalin/urinary creatinine ratio.
      Patients were well balanced for baseline characteristics. Sodium bicarbonate
      infusion increased plasma bicarbonate concentration (p < 0.001), base excess (p <
      0.001), plasma pH (p < 0.001), and urine pH (p < 0.001). Fewer patients in the
      sodium bicarbonate group (16 of 50) developed a postoperative increase in serum
      creatinine compared with control (26 of 50) (odds ratio 0.43 [95% confidence
      interval 0.19-0.98]), (p = 0.043). The increase in plasma creatinine, plasma
      urea, urinary neutrophil gelatinase-associated lipocalin, and urinary neutrophil
      gelatinase-associated lipocalin/urinary creatinine ratio was less in patients
      receiving sodium bicarbonate, (p = 0.014; p = 0.047; p = 0.009; p = 0.004). There
      were no significant side effects. CONCLUSIONS: Sodium bicarbonate loading and
      continuous infusion was associated with a lower incidence of acute renal
      dysfunction in cardiac surgical patients undergoing cardiopulmonary bypass. The
      findings of this pilot study justify further investigation. (ClinicalTrials.gov,
      NCT00334191).

PMID- 19112281
TI  - "Living with dying": the evolution of family members' experience of mechanical
      ventilation.
AB  - BACKGROUND: Communication with families about mechanical ventilation may be more
      effective once we gain a better understanding of what families experience and
      understand about this life support technology when their loved ones are admitted
      to the intensive care unit (ICU). METHODS: We conducted in-depth interviews with
      family members of 27 critically ill patients who required mechanical ventilation
      for > or = 7 days and had an estimated ICU mortality of > or = 50%. Team members
      reviewed transcripts independently and used grounded theory analysis. RESULTS:
      The central theme of family members' experience with mechanical ventilation was
      "living with dying." Initial reactions to the ventilator were of shock and
      surprise. Family members perceived no option except mechanical ventilation.
      Although the ventilator kept the patient alive, it also symbolized proximity to
      death. In time, families became accustomed to images of the ICU as ventilation
      became more familiar and routine. Their shock and horror were replaced by hope
      that the ventilator would allow the body to rest, heal, and recover. However,
      ongoing exposure to their loved one's critical illness and the new role as family
      spokesperson were traumatizing. CONCLUSIONS: Family members' experiences and
      their understanding of mechanical ventilation change over time, influenced by
      their habituation to the ICU environment and its routines. They face uncertainty
      about death, but maintain hope. Understanding these experiences may engender more
      respectful, meaningful communication about life support with families.

PMID- 19112280
TI  - The cardiac output from blood pressure algorithms trial.
AB  - OBJECTIVE: The value of different algorithms that estimate cardiac output (CO) by
      analysis of a peripheral arterial blood pressure (ABP) waveform has not been
      definitively identified. In this investigation, we developed a testing data set
      containing a large number of radial ABP waveform segments and contemporaneous
      reference CO by thermodilution measurements, collected in an intensive care unit
      (ICU) patient population during routine clinical operations. We employed this
      data set to evaluate a set of investigational algorithms, and to establish a
      public resource for the meaningful comparison of alternative CO-from-ABP
      algorithms. DESIGN: A retrospective comparative analysis of eight investigational
      CO-from-ABP algorithms using the Multiparameter Intelligent Monitoring in
      Intensive Care II database. SETTING: Mixed medical/surgical ICU of a university
      hospital. PATIENTS: A total of 120 cases. INTERVENTIONS: None. MEASUREMENTS: CO
      estimated by eight investigational CO-from-ABP algorithms, and CO(TD) as a
      reference. MAIN RESULTS: All investigational methods were significantly better
      than mean arterial pressure (MAP) at estimating direction changes in CO(TD). Only
      the formula proposed by Liljestrand and Zander in 1928 was a significantly better
      quantitative estimator of CO(TD) compared with MAP (95% limits-of-agreement with
      CO(TD): -1.76/+1.41 L/min versus -2.20/+1.82 L/min, respectively; p < 0.001, per
      the Kolmogorov-Smirnov test). The Liljestrand method was even more accurate when
      applied to the cleanest ABP waveforms. Other investigational algorithms were not
      significantly superior to MAP as quantitative estimators of CO. CONCLUSIONS:
      Based on ABP data recorded during routine intensive care unit (ICU) operations,
      the Liljestrand and Zander method is a better estimator of CO(TD) than MAP alone.
      Our attempts to fully replicate commercially-available methods were unsuccessful,
      and these methods could not be evaluated. However, the data set is publicly and
      freely available, and developers and vendors of CO-from-ABP algorithms are
      invited to test their methods using these data.

PMID- 19112282
TI  - Activated protein C improves lipopolysaccharide-induced cardiovascular
      dysfunction by decreasing tissular inflammation and oxidative stress.
AB  - BACKGROUND: Recombinant human activated Protein C (APC) is used as an adjunctive
      therapeutic treatment in septic shock. APC seemingly acts on coagulation
      inflammation interaction but also by decreasing proinflammatory gene activity,
      thus inhibiting subsequent production of proinflammatory cytokines, NO and NO
      induced mediators, reactive oxygen species production and leukocyte-endothelium
      interaction. The hemodynamic effects of APC on arterial pressure and cardiac
      function are now well established in animal models. However, the specific effects
      of APC on heart and vessels have never been studied. OBJECTIVES: To investigate
      the potential protective properties of therapeutic ranges of APC on a rat
      endotoxic shock model in terms of anti-inflammatory and cytoprotective pathways.
      DESIGN: Laboratory investigation. SETTING: University medical center research
      laboratory. INTERVENTIONS: Rats were exposed to lipopolysaccharide (LPS) (10
      mg/Kg intravenous). Endotoxic shock was treated with infusion of saline with or
      without APC (33 microg/kg/h) during 4 hrs. Hemodynamic parameters were
      continuously assessed and measurements of muscle oxygen partial pressures, NO and
      superoxide anion (O2(-)) by spin trapping, of NF-kappaB, metalloproteinase-9 (MMP
      9) and inducible NO synthase (iNOS) by Western blotting, as well as leukocyte
      infiltration and MMP-9 activity were performed at both the heart and aorta level
      (tissue). MAIN RESULTS: APC partially prevented the reduction of blood pressure
      induced by LPS and improved both vascular hyporeactivity and myocardial
      performance. This was associated with a decreased up-regulation of NF-kappaB,
      iNOS and MMP-9. LPS-induced tissue increases in NO and O2(-) production were
      decreased by APC. Furthermore, APC decreased tissue leukocyte
      infiltration/activation as assessed by a decrease in myeloperoxidase and matrix
      metalloproteinase 9 activity. CONCLUSIONS: These data suggest that APC improves
      cardiovascular function: 1) by modulating the endotoxin induced
      proinflammatory/prooxidant state, 2) by decreasing endothelial/leukocyte
      interaction and 3) by favoring stabilization of the extracellular matrix.

PMID- 19112283
TI  - Why is it always about race with you Americans?

PMID- 19112284
TI  - Intra-aortic balloon counterpulsation in septic shock--really?

PMID- 19112285
TI  - Recombinant human activated protein C, package labeling, and hemorrhage risks.

PMID- 19112286
TI  - Do beta-blockers and ACE inhibitors decrease the duration of ventricular
      fibrillation, or cause spontaneous conversion of ventricular fibrillation?

PMID- 19112287
TI  - Prevention measures of ventilator-associated pneumonia.

PMID- 19112288
TI  - Sodium bicarbonate for renal protection after heart surgery: let's wait and see.

PMID- 19112289
TI  - Is the number of reported critical incidents relevant?

PMID- 19112290
TI  - Persistent preoxygenation efforts before tracheal intubation in the intensive
      care unit are of no use: who would have guessed?

PMID- 19112291
TI  - Pressure to perform: is cardiac output estimation from arterial waveforms good
      enough for routine use?

PMID- 19112292
TI  - Going global with sepsis: the need for national registries.

PMID- 19112293
TI  - Lost in translation: family conferences for families that do not speak English.

PMID- 19112294
TI  - "Drug dosing in the intensive care unit: the critically ill are a special
      population too".

PMID- 19112295
TI  - Is transpulmonary thermodilution cardiac output measurement an advance, or just
      another technique in search of an application?

PMID- 19112296
TI  - A face that matters in distress: interface selection for acute noninvasive
      ventilation.

PMID- 19112297
TI  - Toll-like receptor pathway signaling is differently regulated in neutrophils and
      peripheral mononuclear cells of patients with sepsis, severe sepsis, and septic
      shock.

PMID- 19112298
TI  - Etiologies of troponin elevation in critically ill patients with gastrointestinal
      bleeding.

PMID- 19112299
TI  - A fresh look at the MERIT trial: do rapid response systems improve outcome?

PMID- 19112300
TI  - Standardized care for nosocomial pneumonia is a valuable tool to improve patient
      outcomes: how do we get intensivists to listen?

PMID- 19112301
TI  - "We only see what we know"--Johann Wolfgang von Goethe [1749-1832].

PMID- 19112302
TI  - May nutrition be hazardous in sepsis?

PMID- 19112303
TI  - Haloperidol and delirium: management or treatment?

PMID- 19112304
TI  - Can reading a diary improve psychological outcomes in the intensive care unit?

PMID- 19112305
TI  - Genetic variability and outcome in the critically ill: avoiding SNP judgments.

PMID- 19112306
TI  - A Gradus ad Parnassum for adult respiratory distress syndrome--time for a few
      more steps.

PMID- 19112307
TI  - City traffic, acute lung injury, and free enterprise.

PMID- 19112308
TI  - Who is the bad guy in acute respiratory distress syndrome? Neuronal nitric oxide
      synthase, inducible nitric oxide synthase, or both?

PMID- 19112309
TI  - It's all in the gut: introducing the concept of acute bowel injury and acute
      intestinal distress syndrome ....

PMID- 19112310
TI  - Can troponin identify those critically ill septic patients who would benefit most
      from activated protein C treatment?

PMID- 19112311
TI  - Postarrest nitric oxide effect depends on the source.

PMID- 19112312
TI  - Attenuating the effects of cardiac arrest on hepatic drug metabolism: just chill
      out!

PMID- 19112313
TI  - Brain tissue oxygen monitoring in traumatic brain injury: cornerstone of care or
      another brick in the wall?

PMID- 19112314
TI  - Respecting patients' rights at the end of life: problems with the 2006 Uniform
      Anatomical Gift Act.

PMID- 19112315
TI  - No "canary in the coalmine" for intra-abdominal hypertension.

PMID- 19112316
TI  - Prevention of bloodstream infections: basics and beyond.

PMID- 19112318
TI  - Acute kidney injury in critically ill patients.

PMID- 19112319
TI  - Brain tissue oxygen tension is more indicative of oxygen diffusion than oxygen
      delivery and metabolism in patients with traumatic brain injury.

PMID- 19112322
TI  - PEEP is protective against pulmonary microaspiration.

PMID- 19112326
TI  - Blood glucose control in critically ill patients: the impact of diabetes.

PMID- 19112328
TI  - Misguided guidelines on noninvasive thermometry.

PMID- 19112330
TI  - Is the cortrosyn test necessary in high basal corticoid patients with septic
      shock?

PMID- 19112334
TI  - Transplantation of human mesenchymal stems cells into intervertebral discs in a
      xenogeneic porcine model.
AB  - STUDY DESIGN: Experimental and descriptive study of a xenotransplantation model
      in minipigs. OBJECTIVE: To study survival and function of human mesenchymal stem
      cells (hMSCs) after transplantation into injured porcine spinal discs, as a model
      for cell therapy. SUMMARY OF BACKGROUND DATA: Biologic treatment options of the
      intervertebral disc are suggested for patients with chronic low back pain caused
      by disc degeneration. METHODS: Three lumbar discs in each of 9 minipigs were
      injured by aspiration of the nucleus pulposus (NP), 2 weeks later hMSCs were
      injected in F12 media suspension (cell/med) or with a hydrogel carrier
      (Puramatrix) (cell/gel). The animals were sacrificed after 1, 3, or 6 months.
      Disc appearance was visualized by magnetic resonance imaging.
      Immunohistochemistry methods were used to detect hMSCs by antihuman nuclear
      antibody staining, and further performed for Collagen II, Aggrecan, and Collagen
      I. SOX 9, Aggrecan, Versican, Collagen IA, and Collagen IIA and Collagen IIB
      human mRNA expression was analyzed by real-time PCR. RESULTS: At magnetic
      resonance imaging all injured discs demonstrated degenerative signs. Cell/gel
      discs showed fewer changes compared with cell/med discs and only injured discs at
      later time points. hMSCs were detected in 9 of 10 of the cell/gel discs and in 8
      of 9 of the cell/med discs. Immunostaining for Aggrecan and Collagen type II
      expression were observed in NP after 3 and 6 months in gel/cell discs and
      colocalized with the antihuman nuclear antibody. mRNA expression of Collagen IIA,
      Collagen IIB, Versican, Collagen 1A, Aggrecan, and SOX9 were detected in both
      cell/med and cell/gel discs at the time points 3 and 6 months by real-time PCR.
      CONCLUSION: hMSCs survive in the porcine disc for at least 6 months and express
      typical chondrocyte markers suggesting differentiation toward disc-like cells. As
      in autologous animal models the combination with a three-dimensional-hydrogel
      carrier seems to facilitate differentiation and survival of MSCs in the disc.
      Xenotransplantation seems to be valuable in evaluating the possibility for human
      cell therapy treatment for intervertebral discs.

PMID- 19112335
TI  - Parathyroid hormone (1-34) augments spinal fusion, fusion mass volume, and fusion
      mass quality in a rabbit spinal fusion model.
AB  - STUDY DESIGN: The posterolateral rabbit spinal fusion model was used to assess
      the effect of intermittent parathyroid hormone on spinal fusion outcomes.
      OBJECTIVE: To test the hypothesis that intermittent parathyroid hormone (PTH)
      improves spinal fusion outcomes in the rabbit posterolateral spinal fusion model.
      SUMMARY OF BACKGROUND DATA: Spinal fusion is the definitive management for spinal
      deformity or instability, yet despite current technology, 5% to 40% of lumbar
      fusions result in pseudarthrosis. Animal studies have demonstrated enhanced
      fracture healing with the use of PTH, but the effect of PTH on spinal fusion is
      poorly described. METHODS: Forty-four male New Zealand white rabbits underwent
      bilateral posterolateral spine fusion (L5-L6 level). Twenty-two rabbits received
      daily subcutaneous injections of PTH (1-34) (10 microg/kg) and 22 received an
      injection of saline fluid. All were killed 6 weeks after surgery. L5-L6 vertebral
      segments were removed and analyzed with manual bending, faxitron radiography,
      microCT, and histomorphometry. RESULTS: Manual bending identified fusion in 30%
      (control) versus 81% (PTH) animals (P < 0.001). A radiographic scoring system
      ("0" = no bone formation, "5" = full fusion) resulted in an average score of 3.36
      (control) versus 4.51 (PTH) (P < 0.001). MicroCT analysis demonstrated a median
      mass of 3.5 cc (control) (range, 2.25-5.40 cc) versus 6.03 cc (PTH) (range, 4.34
      10.58 cc) (P < 0.001). Histology showed a median percentage bone area of 14.3%
      (control) (n = 12) versus 29.9% (PTH) (n = 15) (P < 0.001). The median percentage
      cartilage was 2.7% (control) (n = 5) versus 26.6% (PTH) (n = 5) (P < 0.01).
      Osteoclast quantification revealed median values of 140.5 (control) (n = 6) and
      345.0 (PTH) (n = 8) (P < 0.001) respectively, and the percentage of osteoblasts
      revealed a median value of 31.4% (control) (n = 6) versus 64.4% (PTH) (n = 8) (P
      < 0.001). CONCLUSION: Intermittent PTH administration increased posterolateral
      fusion success in rabbits. Fusion bone mass and histologic determinants were also
      improved with PTH treatment. PTH has promise for use as an adjunctive agent to
      improve spinal fusion in clinical medicine.

PMID- 19112336
TI  - The efficacy of prostaglandin E1 derivative in patients with lumbar spinal
      stenosis.
AB  - STUDY DESIGN: Randomized controlled trial. OBJECTIVE: To examine the effect of
      limaprost, an oral prostaglandin (PG) E1 derivative, on health-related quality of
      life (HRQOL) in patients with symptomatic lumbar spinal stenosis (LSS), compared
      to etodolac, a NSAID. SUMMARY OF BACKGROUND DATA: Limaprost, an oral PGE1
      derivative, was developed in Japan to treat numerous ischemic symptoms of
      thromboangiitis obliterans (TAO) and LSS. Previous studies have demonstrated the
      effectiveness of limaprost in the symptoms in patients with LSS. However, the
      evidence for effect on patient-reported outcomes, such as patient's HRQOL or
      satisfaction, is limited. METHODS: This study was conducted at 4 study sites in
      Japan. Briefly, inclusion criteria were: age between 50 and 85 years; presence of
      both neurogenic intermittent claudication (NIC) and cauda equina symptoms (at
      least presence of bilateral numbness in the lower limbs); and MRI-confirmed
      central stenosis with acquired degenerative LSS. Limaprost (15 microg/d) or
      etodolac (400 mg/d) was administered for 8 weeks. The primary outcome was Short
      Form (SF)-36, and the secondary outcomes were the verbal rating scale of low back
      pain and leg numbness, walking distance, subjective improvement, and
      satisfaction. RESULTS: A total of 79 participants were randomized
      (limaprost:etodolac = 39:40). Thirteen participants withdrew from the study
      (limaprost:etodolac = 5:8) and 66 completed the study (limaprost:etodolac =
      34:32). Comparisons showed that limaprost resulted in significantly greater
      improvements in the SF-36 subscales of physical functioning, role physical,
      bodily pain, vitality, and mental health. Limaprost was also significantly better
      than etodolac for leg numbness, NIC distance, and subjective improvement and
      satisfaction. In the subgroup analysis stratified by symptom severity, limaprost
      seemed more effective for milder symptoms. No serious adverse effects were
      reported in either treatment group. CONCLUSION: In this study, limaprost was
      found to be efficacious on most outcome measures, such as HRQOL, symptoms and
      subjective satisfaction, in LSS patents with cauda equina symptoms.

PMID- 19112337
TI  - Comparison of BRYAN cervical disc arthroplasty with anterior cervical
      decompression and fusion: clinical and radiographic results of a randomized,
      controlled, clinical trial.
AB  - STUDY DESIGN: A prospective, randomized, multicenter study of surgical treatment
      of cervical disc disease. OBJECTIVE: To assess the safety and efficacy of
      cervical disc arthroplasty using a new arthroplasty device at 24-months follow
      up. SUMMARY OF BACKGROUND DATA: Cervical disc arthroplasty preserves motion in
      the cervical spine. It is an alternative to fusion after neurologic
      decompression, whereas anterior decompression and fusion provides a rigorous
      comparative benchmark of success. METHODS: We conducted a randomized controlled
      multicenter clinical trial enrolling patients with cervical disc disease.
      Ultimately 242 received the investigational device (Bryan Cervical Disc), and 221
      patients underwent a single-level anterior cervical discectomy and decompression
      and fusion as a control group. Patients completed clinical and radiographic
      follow-up examinations at regular intervals for 2 years after surgery. RESULTS:
      Analysis of 12- and 24-month postoperative data showed improvement in all
      clinical outcome measures for both groups; however, 24 months after surgery, the
      investigational group patients treated with the artificial disc had a
      statistically greater improvement in the primary outcome variables: Neck
      disability index score (P = 0.025) and overall success (P = 0.010). With regard
      to implant- or implant/surgical-procedure-associated serious adverse events, the
      investigational group had a rate of 1.7% and the control group, 3.2%. There was
      no statistical difference between the 2 groups with regard to the rate of
      secondary surgical procedures performed subsequent to the index procedure.
      Patients who received the artificial cervical disc returned to work nearly 2
      weeks earlier than the fusion patients (P = 0.015). CONCLUSION: Two-year follow
      up results indicate that cervical disc arthroplasty is a viable alternative to
      anterior cervical discectomy and fusion in patients with persistently
      symptomatic, single-level cervical disc disease.

PMID- 19112338
TI  - Diabetes and cardiovascular disease. The link between blood sugar, heart attacks
      and stroke.

PMID- 19112339
TI  - Arthroscopic surgery may not be best treatment for knee osteoarthritis.

PMID- 19112340
TI  - Discontinuing statin drugs after heart attack may increase risk of death.

PMID- 19112341
TI  - Gastric bypass surgery could provide cure for metabolic syndrome.

PMID- 19112342
TI  - Diabetes care. 10 ways to avoid complications.

PMID- 19112343
TI  - Mayo Clinic office visit. Tinnitus. An interview with Charles Beatty, M.D.

PMID- 19112344
TI  - Going vegetarian? Know your nutritional needs.

PMID- 19112346
TI  - Can finger joints be replaced? Arthritis has left my hands not nearly as
      functional as they used to be.

PMID- 19112345
TI  - I'm certainly not a teenager anymore, so what could be causing the pimples that
      have cropped up on my chin?

PMID- 19112347
TI  - Editorial: TREATING THE WHOLE PATIENT: SELECTIVE SEROTONIN REUPTAKE INHIBITORS
      AND METABOLIC SYNDROME.

PMID- 19112348
TI  - New europe and mental health.

PMID- 19112349
TI  - ['Trauma und entwicklung' folgen von traumatisierung in kindheit und jugend.].
AB  - Cumulative and complex traumatization during development are often the result of
      chronic abuse such as neglect, violence and/or sexual abuse. Chronic abuse leads
      to manifold disorders which may be accompanied by a chronic posttraumatic stress
      reaction as well as developmental disorders. Destructive behavior is one of the
      results. These disorders are seen in the development of emotional disturbances,
      of stress regulation, of memory and the activation or down regulation of certain
      areas of the brain and their neuronal connections.

PMID- 19112350
TI  - [Berufliche rehabilitation in der jugendpsychiatrie.].
AB  - Vocational integration is an important developmental task that must be mastered
      if an adolescent is to function successfully in adult society. Moreover
      adolescence is a period of transition and rapid change, influenced by biological,
      psychological and social interactions. Not only adolescents with manifest
      psychiatric disorders, but also those with a combination of different symptoms
      which don't meet the requirements of a stable diagnosis, need context-sensitive
      support. In 1996 the youth-specific activities of pro mente Karnten (an
      association offering different support to people with mental disorders) became a
      stand-alone association, dedicated to the special-needs of children's and
      adolescent's mental and social health. In the field of vocational rehabilitation,
      pro mente Jugend started with a 6-month (since 2001 12-month) prevocational
      training (Works) for 18 participants, financed by the Bundessozialamt and
      targeting a vocational integration after the course. This program proved helpful
      for adolescents with moderate handicaps and learning disabilities, whereas
      clients with severe mental disorders (e.g. psychosis and affective disorders)
      couldn't be supported adequately within 6 nor within 12 months. These people have
      shown the poorest vocational outcome. Therefore, rapid vocational integration is
      not a realistic aim for all clients. According to our experience, pro mente
      jugend makes efforts to develop and provide different out-patient services,
      bridging the broad transition from hospital based programs to the first labour
      market - corresponding to the special needs of the clients. At each level,
      different outcomes are targeted: there are day-care, work therapy and social
      participation, as well as prevocational training, apprenticeship, integration or
      transition employment. One of this modules already exists and offers
      apprenticeship to disadvantaged adolescents. A day-care center for clients with
      psychotic and affective disorders is being planned currently. For implementing
      this concept, pro mente Jugend will consider some principles: near to the clients
      needs and shared-decision making with them - based on ongoing assessment,
      diagnostic and planning; consumer-driven Case Management to provide the
      sufficient support in time; respecting people's right to work and addressing
      their strengths and preferences; empowerment and full participation. Because of
      the governments budgetary limits, we intend to cooperate with responsible parts
      of the civic society and companies, which are ready to engage in social
      activities.

PMID- 19112351
TI  - [Konzepte der fruhpravention von suchterkrankungen.].

PMID- 19112352
TI  - Update of suicide trends in croatia 1966-2002.
AB  - OBJECTIVE: To analyze trend the suicide rates in Croatia during the pre-war
      period of socialistic Yugoslavia (1966-1990), war period in the former Yugoslavia
      (1991-1995) and the post-war period of Croatian independence and democratization
      (1996-2002). METHOD: Using official suicide statistics, this study examined
      suicide rates in Croatia over a 36-year span (1966 to 2002) as a function of
      gender, age, marital status, time, war and social changes. Suicide rates were
      displayed graphically and compared with some neighbouring countries (Slovenia,
      SCG, Hungary and Italy). RESULTS: During the period of socialistic Yugoslavia,
      suicide rate in Croatia was constantly increasing with small variations. During
      the war time suicides with firearms were significantly increased. Since 1993 (the
      period of independence and democratization) there has been a trend of evident
      decrease in total suicide rate. CONCLUSION: This study demonstrated that Croatia
      has still had high suicide rates with declining trend since 1993, probably
      related to democratization, more national, religious and cultural rights, better
      availability of SSRIs and systemic campaign for education of general
      practitioners for early recognition and treatment of depressive disorders.

PMID- 19112353
TI  - Psychiatric and somatic complications and pharmacological treatment in patients
      with dementia.
AB  - One hundred and one patients with dementia, treated at Psychiatric department of
      GH Bjelovar were studied regarding the sort and frequency of complications, the
      evidence of other psychiatric or physical illnesses and psychopharmacological
      therapy. Of all the patients diagnosed with dementia, 21.78% were diagnosed with
      primary dementia, 70.3% with secondary dementia and 7.92% with combined (both
      primary and secondary) dementia. The number of patients diagnosed with vascular
      and primary dementia and the number of the registered complications vs. the so
      called other psychiatric diagnoses accompanying dementia reflects the
      difficulties in diagnosing Alzheimer's disease and the complications of dementia.
      The results of therapy are thoroughly discussed.

PMID- 19112354
TI  - Usage of diagnostic questionnaire for depressive patients versus center for
      epidemiologic studies of depression scale in breast cancer patients.
AB  - OBJECTIVE: The aim of the study was to examine the agreement and differences
      between Diagnostic Questionnaire for Depressive Patients according to 10th
      revision of International Statistical Classification of Diseases and Related
      Health Problems (ICD-10) and Center for Epidemiologic Studies Depression Scale
      (CES-D). METHODS: Participants were 115 breast cancer female patients recruited
      in specialised cancer hospital radiotherapy unit. Depression was measured with
      CES-D, 20-item self-report scale designed to measure depressive symptoms in
      community. Score of >/= 16 indicated clinically relevant depression. Depression
      was also measured with Diagnostic Questionnaire for Depressive Patients based on
      the criteria of 10th revision of International Statistical Classification of
      Diseases and Related Health Problems. RESULTS: By using Diagnostic Questionnaire
      for Depressive Patients we established that of 115 patients 47 (40.9%) fulfils
      the criteria for depressive episode and that in the division by type of
      depressive episode 5 (10.6%) has mild, 22 (46.8%) has moderate and 20 (42.5%) has
      severe depressive episode. By CES-D 42 (36.5%) patients were considered
      clinically depressive. Kappa coefficient shows good agreement between two
      measures (kappa=0.799; p=0.000). CONCLUSION: CES-D and Diagnostic Questionnaire
      for Depressive Patients show good agreement in assessment of depression but in
      clinical setting assessment should be made with diagnostical instruments as
      Diagnostic Questionnaire for Depressive Patients.

PMID- 19112355
TI  - SUICIDE, INDUCED ABORTION AND STANDARDIZED DEATH RATE IN CROATIA In relation to
      neighbouring countries: Hungary, Slovenia and Italy.
AB  - OBJECTIVE: Suicides and induced abortions are primarily both premature deaths.
      Standardized death rates often show the certain level of medical standards in the
      different countries. The aim of this paper was to determine suicide rates in
      Croatia and its neighbouring countries (Hungary, Slovenia and Italy) associated
      with induced abortions and standardized death rates Method: It was a register
      linkage study. Information on suicides of women in Croatia, Hungary, Slovenia and
      Italy were linked with induced abortions and standardized death rates in these
      countries. Nationwide data in Croatia, Hungary, Slovenia and Italy in the period
      1996-2002 i.e. the latest available data for each county was used. RESULTS: There
      were suicide rates in women: Croatia (2000)-10.3, Hungary (1999)-15.4, Slovenia
      (1999)-13.4 and Italy (1998)-3.6. There were induced abortions (% of live born
      children): Croatia (2002)-17.8, Hungary (2002)-69.7, Slovenia (2002)-49.6 and
      Italy (2002)-24.0. There were standardized death rates (1/10.000 population):
      Croatia (1998)-113.8, Hungary (1996)-109.3, Slovenia (1996)-109.3 and Italy
      (1996)-70.7. CONCLUSIONS: The Croatian suicide rate and induced abortions have
      been lower than in Hungary and Slovenia. Croatia has been at the last place
      according to induced abortions but Croatia has been at the first place due to
      standardized death rates.

PMID- 19112356
TI  - Plasma level of valproic Acid in treatment of severe cases of schizoaffective
      psychoses and rapid cycling bipolar disorders.

PMID- 19112357
TI  - Editorial: MODERN PSYCHOPHARMACOTHERAPY BETWEEN GENETIC DETERMINISM AND FREEDOM
      OF CHOICE.

PMID- 19112358
TI  - Risperidon vs. Other antipsychotics in schizophrenia: the assessment of patients'
      attitudes.
AB  - OBJECTIVE: The multicentric prospective study was conducted to examine patients'
      attitudes toward risperidone in comparison to any previous antipsychotic
      treatment. SUBJECTS AND METHOD: Ninety three subjects with a schizophrenia or
      schizoaffective psychotic disorder (ICD-10), previously treated with any
      antipsychotics, were included in the study and treated with risperidone during 8
      weeks. At the baseline, symptoms were assessed by PANSS and history of previous
      medication was recorded. At the end of the study, patients' attitudes were
      examined by eight-items questionnaire and PANSS was scored. RESULTS: Ninety five
      percent of patients previously treated with FGA (80%), SGA(5%) or combination
      (10%) completed the study, with improvement expressed in 62% change of the total
      PANSS score. Eight items questionnaire yielded risperidone to be superior to
      other regarding all questions. For continuation of the treatment, 83% of patients
      had chosen risperidone. CONCLUSION: Patients' attitudes and satisfaction with
      treatment should be monitored carefully because it appears to be related strongly
      to their readiness to take medication as prescribed, and thereby to outcome.

PMID- 19112359
TI  - Features in families of autistic children and healthy controls in comparison.
AB  - Objectives. Standardized assessment of family features is not used routinely
      although these factors may play an important role in the course of psychological
      disorders in children. Thus the aim of the present study was to investigate
      families of autistic children with regard to differences within the features in
      their families using standardized instruments. Methods. The families of 115
      autistic children (55 boys, 60 girls) diagnosed (aged 6-12y) by means of the
      Mannheim Parents Interview (Esser et al., 1989) were included for evaluation and
      compared with a matched, healthy control group. Parents were asked to complete a
      questionnaire assessing the family features ("Familienklima-Testsystem",
      Schneewind et al., 1985). Results. The results show that there are significantly
      more conflicts in families whose children are autistic than in control families.
      Compared to the matched healthy control group, there is a significant lack of
      organization and coherence in the dissocial group. Conclusions. Our results
      strongly suggest, that there seems to be a significant influence of psychosis on
      the family's coherence and organization which should make therapists focus their
      efforts not only on the "index" children as such but also on their families.

PMID- 19112360
TI  - Characteristics of posttraumatic stress disorder in ex prisoners of war.
AB  - Post Traumatic Stress Disorder is a frequent consequence of surviving the stress
      of the war. The majority of research studies confirm that the severity, duration
      and the proximity to the traumatic events have significant influence on the
      outcome of surviving psychological trauma. There is also evidence that the
      prisoners of war who have survived severe, repetitive traumatization will develop
      PTSD more frequently, and that the characteristics and the severity of symptoms
      is more serious compared with the veterans of war who did not survive
      imprisonment. This paper analyzes the presence of the symptoms of PTSD according
      to frequency in a group of former prisoners of war and a group of war veterans
      who did not experience imprisonment. The research sample is comprised of subjects
      who were selected by the method of randomized stratified sample and divided an
      experimental and control group. Experimental subgroup E1 consist of 50 former
      prisoners of war who have sought psychiatric help after being released from the
      prisons, and subgroup E2 consist of 50 former prisoners of war who never sought
      psychiatric assistance. Control group is divided in subgroup K1 that consist of
      30 veterans of war who did not survive imprisonment, and who have occasionally
      sought psychiatric assistance after the war, and subgroup K2 that consist of 30
      veterans of war who did not survive imprisonment and who never sought psychiatric
      assistance. All subjects were male, none of them had any prior psychiatric
      history. The instruments used in the study were the following: general and
      sociobiographic questionnaire designed by the authors, traumatic events
      questionnaire which is a modified version of the Harvard Trauma Questionnaire,
      PTSD questionnaire designed according to DSM IV diagnostic criteria. Results in
      relation to degree of traumatic experience demonstrate that there is a
      significant statistical difference (P<0.005) between the experimental and control
      group. PTSP is statistically significantly more represented among the former
      prisoners of war than among the war veterans who were not detained in camps
      (P<0.05). Average scores for all symptom clusters (fear and helplessness, re
      experiencing symptoms, avoidance symptoms, and hyper-arousal symptoms) were
      higher in the experimental group than in a control group.

PMID- 19112361
TI  - [Die entwicklung der psychiatrie in oberosterreich 1960 - 2000.].
AB  - Psychiatric reforms in Upper Austria have considerably improved the quality of
      life of psychiatric patients. Modernizing the status of acute psychiatric
      departments based on a bio- psycho-, social concept implemented multidimensional
      approach in diagnostics and therapeutic methods applied by multiprofessional
      teams. Prophylactic procedures and rehabilitation programs have minimized
      chronification of psychiatric diseases. By "late rehabilitation programs"
      increased autonomy, more individualized planning of life processes could be
      achieved even with "chronic" patients. We do not see any need to confine
      "chronic" psychiatric patients in psychiatric hospitals. These patients are cared
      for, socially integrated by special rehabilitation measures and professional
      rehabilitation in community - based services and units of Pro Mente Upper Austria
      - a non-profit organization. Problems are decreased duration of stay in
      psychiatric hospitals, increased admission rates when the number of beds in
      psychiatric departments was considerably decreased in the course of psychiatric
      reforms in Austria. In our province - Upper Austria - these problems are of
      lesser importance because private non-profit organizations like Pro Mente Upper
      Austria have provided a variety of community-based services (mental health
      centres, day clinics, housing facilities and special services for drug addicts
      and geriatric patients ) in ever increasing numbers. Still there is need of
      further development of community-based services provided by specially trained
      professionals. These services are financed mainly by the state, the provincial
      government, the labour market services and to a small degree by funds of the
      European Union. In these days of reduced social budgets of the state and social
      departments of provincial governments it is not easy to keep our standards and
      meet the increased needs of our clients.

PMID- 19112362
TI  - Anticipation of total solar eclipse and suicide incidence.
AB  - Around the total solar eclipse of August 11 1999, suicide incidence decreased in
      Timis county, Romania, a region crossed by the path of totality and subject to
      eclipse-trekking, whereas no such decrease was observed in Latvia, where only a
      partial eclipse was observed. Collective anticipation of a positive event could
      have a preventive effect on suicide incidence.

PMID- 19112363
TI  - Cholesterol serum levels in violent and non-violent young male schizophrenic
      suicide attempters.
AB  - Our prospective study used a case-control design to compare serum total
      cholesterol concentration, in young males with schizophrenia (DSM-IV) after non
      violent (n - 13) suicide attempts and violent suicide attempts (n - 13), also
      included non-suicidal controls, also with diagnosis of schizophrenia (n - 13).
      Patients with a diagnosis of alcohol abuse and with cholesterol-lowering therapy
      were excluded. The aim of this study was to evaluate whether men after a violent
      suicide attempts have different serum cholesterol concentrations than those who
      attempted suicide by non-violent methods. Using the Scheffe test, a significant
      difference in serum cholesterol (p=0.01) was revealed between the group of
      violent and non-violent suicide attempters and between the violent suicide
      attempters and the control group (p<0.01). Our findings suggest that low levels
      of cholesterol are associated with increased tendency for impulsive behavior and
      aggression and contribute to a more violent pattern of suicidal behavior.

PMID- 19112364
TI  - Transgenerational damnation of divorce.
AB  - In this work transgenerational transmission is defined with emphasis on
      transgenerational transmission of divorce. Sometimes, divorces are like family
      damnation repeating in the family tree of one family. Decisive factors for that,
      according to professionals, are adoption of a model of parenthood behaviour or
      unconscious transmission of the representation of the family self that children
      manifest in their mature age. This work presents a case of a seven years old girl
      Maria in the system of transgenerational transmission divorce of the marriage of
      her parents. Maria suffered from symptoms of school phobia and in this symptoms
      lies the "hidden" wish of her mother for divorce as transgenerational
      representation of family self of her primary family, which conditioned
      generational compulsion of repetition through the female line. Application of
      psychodynamic oriented psychotherapy in this case gave very good results.

PMID- 19112365
TI  - COLLEGIUM INTERNATIONALE NEURO-PSYCHOPHARMACOLOGICUM (C.I.N.P.) 24th CONGRESS
      (Paris, France, 20-24 June 2004).
AB  - The 24th C.I.N.P. meeting was held in Paris, France, from June 20-24, 2004. The
      opening ceremony and welcome reception was chaired by Professor Herbert Y
      Meltzer, Vanderbilt University, Nashville, TN, USA, President of C.I.N.P., and a
      new president was elected (Professor Brian E. Leonard, Ireland). Congress
      included the rich social program, combined with lectures of invited speakers,
      speeches and awards. There were 6650 registered participants all over the world.
      The meeting consisted of 4 plenary lectures (held by Professor FE Bloom,
      Department of Neuropharmacology, The Scripps Research Institute, La Jolla USA,
      Professor HY Meltzer, Vanderbilt University, Nashville, TN, USA, Professor CL
      Masters, The University of Melbourne, and the Mental Health Research Institute of
      Victoria, Melbourne, Australia, and Professor JP Changeux, CNRS URA 2182
      Recepteurs and Cognition, Paris, France), 69 symposia, 5 synthesia, 25 satellite
      symposia, 2 electronic interactive sessions, 6 meet the expert sessions, 11
      sessions that were held under the name breaking scientific news, 6 workshops, 5
      joint meetings, and 2 poster sessions with 657 posters. Posters were displayed
      for 2 days between 12.00 to 18.00 h, and presenters were available between 16.30
      and 18.00 h to answer the questions. Abstracts from the congress were published
      in International Journal of Neuropsychopharmacology, vol 7, Supplement 1, June
      2004. The 24th Collegium Internationale Neuro-Psychopharmacologicum (C.I.N.P.)
      Congress introduced some new exciting data, summarized some new knowledge, and
      its goal was to connect the preclinical and clinical data and to introduce some
      news into clinical practice. The smaller part of the congress that I was able to
      follow was well organized, and very good attended, with diverse topics, covering
      all aspects of neuropsychopharmacological research. The sponsorship by the
      pharmaceutical industries was visible only in the selected sponsored symposia.

PMID- 19112366
TI  - Selegiline and methylphenidate in treatment of ADHD.
AB  - A lack of perseverance, poor attention and poorly modulated behaviour are
      important criteria of Attention deficit hyperactive disorder. Instructions often
      have to be repeated, sometimes even by different family members before a child
      with ADHD attends and complies. The hyperkinetic child might cause less
      disagreement in families with high coherence. Methylphenidate is quite effective
      in psychopharmacological treatment of ADHD. Selegiline has a longer half-life
      time and seems to be as effective as Methylphenidate. Families of 15 boys (age 6
      to 12 years), diagnosed with ADHD using the Mannheim;s Parents Interview and
      teacher;s form of the Conners Scale, who were treated with Methylphenidate, were
      compared with a matched group of 15 boys treated with Selegiline. Methylphenidate
      was administered four times/day, Selegiline was administered twice a day only.
      The Mann-Whitney-U-Test suggested, that there was no significant difference of
      improvement between Selegiline and Methylphenidate.

PMID- 19112367
TI  - About the association between attachment and temperament at the age of 6 months.
AB  - OBJECTIVES: This study investigates the association between the mother-child
      attachment (0.6 years) and the child;s temperament at that age. A significant
      correlation of secure attachment and easy children as well as of insecure
      ambivalent/avoidant attachment and difficult children was expected. METHODS: 105
      healthy children, aged 0.5-0.8 months, were assessed by a semi-structured
      interview, based on Axis II (Zero to Three, 1994), and the guidelines of Thomas
      et al. (1968). Data were compared by correlation analysis and Mann-Whitney U
      Test. RESULTS: Ambivalent attachment is highly associated with "difficult" and
      "slow to warm up" temperament. There is almost no association between secure
      attachment and easy children. Avoidance does not seem to be associated with
      temperament factors. CONCLUSIONS: Insecure attached children seem to show
      temperament disorders and vice versa. This circular process can be stopped by
      attachment improving programs: improving the attachment may make children "easy".
      Secure attachment may not stand for easy children. Altogether, attachment and
      temperament are two separate behavior conducts, that are only poorly associated.

PMID- 19112368
TI  - Secondary victimization of war veterans with post-traumatic stress disorder: the
      croatian experience.
AB  - This paper discusses the phenomenon of secondary victimization or revictimization
      of Croatian war veterans with post-traumatic stress disorder (PTSD). This
      revictimization is mainly characterized by a disappointing institutional response
      from the helping professions, together with a lack of social recognition and
      support after the war. Also, we describe the "blaming the victim" process in
      which the veterans with PTSD were accused for bringing their maladies on
      themselves due to their premorbid psychological characteristics. This paper
      traces the origins of these phenomena in Croatia and compares them to other
      traumatized populations throughout the world, adding to the established body of
      knowledge which confirms that denial of PTSD in war veterans is a widespread
      social occurrence which spans over history, crossing national and cultural
      boundaries.

PMID- 19112369
TI  - Torture victims and mechanisms of coping with stress.
AB  - The research has been performed over the torture victims during the aggression
      against Bosnia and Herzegovina. All patients-torture victims were of a different
      nationality as compared to the aggressors. The goal of the study was to register
      strategies of coping with stress in patients-torture victims before and after a
      three- month long treatment. All tested patients were psychologically tortured
      and physically abused. Strategies of coping with stress registered in tortured
      victims before the beginning of treatment and after a three-month combined
      psychotherapeutic and pharmacoterapeutic treatment. After completion of
      treatment, there was a significant increase in frequency of seeking social
      support, whereas accepting of responsibility was significantly decreased.
      Positive coping strategies like self-control, positive reinterpretation and
      planned problem-solving show a slight increase after the treatment, but the
      resu1ts are not significant.

PMID- 19112371
TI  - HISTORY OF PSYCHIATRY, Introduction.

PMID- 19112370
TI  - Pain mask in masked depression in the form of selective toothache - own
      experience - case report.
AB  - My patient visited many stomatologists due to various toothaches. The author in
      detailed psychiatric examination made the diagnosis of masked endogenous
      depression.

PMID- 19112372
TI  - Selected aspects of a century of psychiatry in europe.

PMID- 19112374
TI  - [Psychosomatische behandlung chronischer schmerzpatientinnen.].

PMID- 19112373
TI  - Psychiatry in the danube regions - a historic perspective: austria.

PMID- 19112376
TI  - History and development of slovak psychiatry.

PMID- 19112375
TI  - Key moments in the history of czech psychiatry.
AB  - 1783 - The Austrian Emperor Joseph II. established a department for mentally ill
      priests in the hospital of the Merciful Brothers in Prague. 1790 - Based on the
      Emperors decision, a new hospital was opened in Prague. A new two-storey building
      was used exclusively for treatment of the mentally ill patients. 1821 - Lectures
      about insanity were opened at Prague University. 1844 - A New house (nowadays a
      psychiatric University department) was established. Building of psychiatric
      hospitals: 1863 Brno-Cernovice, 1870 Kosmonosy, 1880 Dobrany, 1887 Oparany, 1889
      Opava, 1890 Horni Berkovice, 1892 Sternberk, 1906 Kromeriz, 1902 Jihlava, 1908
      Praha-Bohnice. 1904 - A Journal, later called Czechoslovak Psychiatry was
      founded. 1919 - The Czech, later the Czechoslovak and latest the Czech
      Psychiatric Society were established. 1955 - Specialization for psychiatry. 1956 
      Separation psychiatry and neurology. Progress in the out-patient care from 1, 0
      psychiatrist per 100.000 inhabitants (1963) to 4, 5 (1995). Form 1989 accent on
      human and patient's rights and ethical principles, end of abuse of psychiatry.
      1993 - First community based-services.

PMID- 19112377
TI  - History of bulgarian psychiatry.

PMID- 19112378
TI  - History of psychiatry in ukraine.
AB  - Important directions of the development of psychiatry in Ukraine are given. The
      historical review of the period of the formation of psychiatry as a science and
      assistance to patients in Ukraine gives the opportunity to evaluate the existing
      level of mental health care as well as its historical background.

PMID- 19112379
TI  - Past and present of psychiatric care in Russia.

PMID- 19112380
TI  - Polish psychiatry in the wake of social changes.
AB  - The aim of this paper is to present some characteristic facts concerning the
      history of psychiatry in Poland. Those facts have been selected as to illustrate
      the two obvious but not often expressed theses: 1. the history of psychiatry in
      Poland has been closely linked with the mainstream of Western thought, social and
      philosophical ideas of the time; 2. development of psychiatry and psychiatric
      care depend on the political history of the country. The background factor that
      greatly influenced that development was the partition of Poland between Russia,
      Prussia and Austria, which lasted well over one hundred years.

PMID- 19112381
TI  - The past and present of croatian psychiatry.

PMID- 19112382
TI  - History of danube symposia of psychiatry, 1964 - 2002.

PMID- 19112383
TI  - Tryptophan administration in rats enhances phagocytic function and reduces
      oxidative metabolism.
AB  - OBJECTIVES: Since the tryptophan-derived metabolites serotonin and melatonin have
      been shown to possess reinforcing and/or antioxidant properties in the immune
      system, this investigation was aimed at determining the possible effect of a 7
      day administration of tryptophan (125 mg/kg b.w.), the precursor of both the
      neurotransmitter and the indole, on the phagocytosis and free radical scavenging
      of peritoneal macrophages from adult male Wistar rats. METHODS: Phagocytosis was
      measured by the latex-bead phagocytosis index (PI), i.e., the number of latex
      beads ingested by 100 macrophages, the phagocytosis percentage (PP), i.e., the
      percentage of cells that had phagocytosed at least one latex bead, and the
      phagocytosis efficiency (PE), i.e., the ratio PI:PP which indicates how
      effectively the phagocytes ingested the particles. Oxidative metabolism was
      measured by the nitroblue tetrazolium (NBT) reduction test. RESULTS: In control
      conditions, PI, PP, and PE significantly increased during the dark period, while
      the superoxide anion levels underwent a significant reduction. Tryptophan
      treatment significantly raised the phagocytosis parameters in a general fashion,
      as well as decreasing the oxidative metabolism with respect to the control
      values. Also, there was a significant rise in the MESORs of the PI and PE (of
      around 16% and 12%, respectively), the MESOR of the percentage of NBT reduction
      was significantly reduced (19%). CONCLUSION: Orally administered tryptophan
      enhanced the phagocytic response and detoxification of superoxide anion radicals
      derived from this immune function in the peritoneal macrophages of rats, very
      probably through its conversion to the immunoregulatory molecules, serotonin and
      melatonin.

PMID- 19112384
TI  - Trazodone improves the results of cognitive behaviour therapy of primary insomnia
      in non-depressed patients.
AB  - OBJECTIVES: Cognitive behaviour therapy (CBT) of primary insomnia is frequently
      combined with various pharmacological treatments, including sedative
      antidepressants. The present study was undertaken to evaluate the clinical
      efficacy of CBT, singly and combined with trazodone pharmacotherapy, for primary
      insomnia. DESIGN AND SETTING: Randomised, comparative clinical trial, at a single
      academic medical centre. METHODS: Twenty outpatients (15 women, 5 men) with
      chronic primary insomnia were randomly assigned to CBT or CBT +100mg trazodone
      and treated for 8 weeks. The treatment outcome was estimated by mean changes from
      baseline in self-reported clinical scales, sleep continuity data and sleep
      architecture parameters. RESULTS: All patients perceived significant subjective
      sleep improvements. Sleep latency significantly shortened (p=0.03), sleep
      efficiency increased (p=0.004) and the total sleep time was significantly
      prolonged (p=0.006) after the CBT treatment in both groups. Sleep architecture
      showed that the combined approach (CBT + trazodone) resulted in a significant
      increase in slow wave sleep duration compared to treatment by CBT only (p=0.04).
      CONCLUSIONS: CBT, singly and combined with the sedative antidepressant trazodone,
      is effective for the short-term management of chronic primary insomnia. Trazodone
      combined with CBT significantly increases slow wave sleep duration and this
      influence seems to be unrelated to its antidepressant effect.

PMID- 19112385
TI  - The phylogenesis and ontogenesis of the human pharyngeal region focused on the
      thymus, parathyroid, and thyroid glands.
AB  - The pharyngeal (branchial) region represents a classic example where the
      relationship between ontogenesis and phylogenesis has been demonstrated. It is a
      region where the development of gills during ontogenesis of all chordates has
      been recapitulated. In the process of evolution the pharyngeal region has
      undergone marked changes. While it functioned to ensure blood oxygenation and
      regulation of a constant internal environment in aquatic animals, it had to adapt
      to new and more complex functions in terrestrial vertebrates. The lungs have
      taken on the main role of blood oxygenation and the salivary glands now regulate
      ionic balance. The immune organs in mammals such as the thymus and the palatine
      tonsil, endocrine organs such as the parathyroid glands and the parafollicular
      cells of the thyroid gland, which produces calcitonin (originally as independent
      ultimobranchial bodies), as well as a part of the ear developed from the
      pharyngeal region. This article briefly summarizes the current knowledge
      regarding the phylogenesis and development of the human thymus, parathyroids, and
      the thyroid gland with a focus on the influence of neural crest cells during
      development.

PMID- 19112386
TI  - The GPR54-Kisspeptin complex in reproductive biology: neuroendocrine significance
      and implications for ovulation induction and contraception.
AB  - KISS1 encodes the kisspeptin (KP) family of peptides which were originally
      characterised as potent antimetastatic agents in breast cancer and malignant
      melanoma cells. One member of this family of arginine-phenylalanine amide
      peptides, KP-54, was subsequently identified as the natural ligand for the G
      protein coupled receptor-54 (GPR54). In addition to its importance as a
      metastatic suppressor, KP has been found to play a major neuroregulatory role in
      governing endogenous gonadotropin release by its modulation of the hypothalamic
      pituitary-gonadal (HPG) axis. In humans, KISS1 mRNA has been localised to the
      hypothalamic anteroventral periventricular nucleus and arcuate nucleus. Although
      GPR54 is expressed in human pituitary cells, it is not presently known if
      gonadotrope cells themselves are targets for significant KP activity. It was
      recently shown that full disruption of the KP/GPR54 complex resulted in
      hypogonadotropic hypogonadism. Indeed, evidence now suggests that KP/GPR54
      signalling during gestation is necessary for sexual differentiation and
      implicates activation of the KP/GPR54 complex as the single most important
      upstream event regulating GnRH release. Several compelling studies have placed KP
      as the leading candidate molecule responsible for initiating puberty, making this
      receptor-ligand complex of fundamental importance to the neuroendocrinology of
      reproduction. Here, we discuss key KP/GPR54 discovery events and present an
      evolution of KP biology in the context of recent animal and human experimental
      work. With evidence pointing to proper KP/GPR54 signalling as the principal
      trigger for activation of GnRH neurons and subsequent ovulation, elucidation of
      how this pathway is modulated is likely to bring novel pharmacologic strategies
      for fertility treatment (and contraception) within reach. Because the
      physiological significance KP is now acknowledged to extend well beyond cancer
      biology (and may also contribute to the pathophysiology of pre-eclampsia), KP
      represents an exciting research theme in human reproductive biology and
      neuroendocrinology.

PMID- 19112387
TI  - The expression of ghrelin in somatotroph and other types of pituitary adenomas.
AB  - OBJECTIVES: It has been suggested that ghrelin synthesized locally in pituitary
      regulates the function and growth of pituitary cells in autocrine/paracrine way
      and might be an important factor of pituitary tumorogenesis. The expression of
      ghrelin receptor in neoplastic cells of pituitary adenomas has also been
      demonstrated. In vitro studies confirmed that ghrelin stimulates the
      proliferation of somatotroph cells in GH3 cell line. The presence of both ghrelin
      mRNA and protein was detected in a number of benign and malignant neoplasms as
      well as in neoplastic cells of the tissues which do not express ghrelin in
      physiological conditions. This study showed the presence of ghrelin mRNA and its
      protein in different types of pituitary adenomas. DESIGN: The samples of 37
      pituitary adenomas were obtained during standard neurosurgical tumor removal. The
      study tissues included 20 somatotroph tumors (15 patients treated and 5 patients
      untreated with octreotide LAR before the surgery), 12 nonfunctioning adenomas, 4
      prolactinomas and 1 ACTH-secreting tumor. The control included samples of normal
      mucous membrane of the stomach and normal pituitaries. Expression of ghrelin mRNA
      was studied in 28 pituitary adenomas by RT-PCR. Immunohistochemical evaluation of
      ghrelin presence was performed in 34 tumors. RESULTS: The presence of ghrelin
      gene transcripts was demonstrated in 10 out of 15 examined somatotroph tumors
      (obtained from patients treated with octreotide LAR before the surgery) and also
      in 2 out of 4 samples of prolactinomas, 7 out of 8 of nonfunctioning tumors and
      in 2 samples of normal pituitary. Immunohistochemical analyses revealed the
      presence of the protein in all 5 examined somatotroph tumors obtained from
      patients not treated prior to the surgery and in 10 out of 15 tumors obtained
      from patients treated with octreotide LAR. The peptide was detected also in 10
      out of 12 examined nonfunctioning tumors and in 2 examined PRL-secreting tumors.
      The immunostaining for ghrelin was not shown in normal pituitaries. CONCLUSIONS:
      The study demonstrated that ghrelin gene is expressed in somatotroph adenomas,
      both treated and untreated with octreotide LAR before the surgery, and also in
      other types of pituitary adenomas (prolactinomas and nonfunctioning adenomas).

PMID- 19112388
TI  - The evaluation of nociceptive intensity by using free radicals direct measurement
      by EPR method in the tail of anaesthetized rats.
AB  - OBJECTIVES: The aim of the study was to demonstrate the ability to measure free
      radicals and singlet oxygen, using EPR methods, in the tail of anaesthetized
      rats. The advantage of this method lies in the potential for continuous
      evaluation of free radicals and singlet oxygen during nociceptive processes.
      METHODS: Electron paramagnetic (spin) resonance (EPR/ESR) was used. DMPO and PBN
      as spin traps and thermal mechanical pulp (TMP) as a spin detector of singlet
      oxygen were used. Thirty-one adult male (Wistar) rats were used for the
      experiments. They were housed according to principles of good laboratory
      practice. The animals were stimulated for 10 minutes on 5 consecutive days by
      using clamps on the hind limbs. During the EPR measurement they were
      anaesthetized with a mixture of ketamine and xylazine. Hydroxyl and nitroxide
      free radicals, as well as singlet oxygen were measured. RESULTS: After
      nociceptive stimulation, free hydroxyl radicals were increased as well as free
      nitroxide radicals. Singlet oxygen was also increased after nociceptive
      stimulation. Antioxidants significantly decreased the increase in hydroxyl
      radicals after nociceptive stimulation. CONCLUSIONS: Our results confirmed an
      increase in free radicals and singlet oxygen after nociceptive stimulation and a
      reduced increase after application of antioxidants. Direct EPR methods were first
      used in the tail of anaesthetized rats and represent an extremely useful tool for
      the evaluation of pain intensity in living animals.

PMID- 19112389
TI  - The effect of leptin on the tonic secretion of gonadotropins in the female rats.
AB  - OBJECTIVES: This study is an attempt to determine, the in vivo action of leptin
      on this hypophysiotropic hypothalamic area, by evaluating the concentrations of
      luteinizing hormone (LH) and follicular stimulating hormone (FSH) in the serum.
      METHODS: The experiments were done by stereotaxic injection of recombinant rat
      leptin (rrleptin) into the third cerebral ventricle (V3) of adult female Wistar
      rats. Subjects were divided into five groups. Group A included normal intact
      animals. In Group B, the rats were stereotaxically administered with rrleptin in
      the V3. The rats, in Groups C, D and E, were subjected to electrolytic lesion of
      the arcuate nucleus (ARC), of the ventromedial nucleus (VMH) and of both of these
      hypothalamic nuclei, respectively. Immediately after the electric lesion, they
      were intracranially injected with rrleptin. Blood samplings for serum LH and FSH
      levels estimation were performed three times: 1) just before any stereotaxic
      procedure, 2) six hours, and 3) twenty-four hours after leptin administration.
      RESULTS: The results showed that serum LH levels increased dramatically in group
      B, six hours after leptin administration. The LH levels in Groups C, D and E
      presented the same pattern with a lower peak. The FSH levels were doubled six
      hours after leptin administration in all groups without any exception. Both LH
      and FSH serum levels reverted to the initial basic levels after 24 hours.
      DISCUSSION: The significant conclusion derived from this study is that ARC and
      VMH, which are responsible for controlling the tonic secretion of gonadotropins,
      respond in a different way for the FSH and LH secretion. This also suggests that
      some other mechanism(s) or factor(s) may additionally participate in the control
      of the tonic component of FSH secretion.

PMID- 19112390
TI  - The choice of therapy in acromegaly: results of treatment at a tertiary care
      hospital.
AB  - OBJECTIVE: The aim of our study was to investigate the characteristics of
      acromegalic patients diagnosed at a tertiary University Hospital and to evaluate
      the results of the recommended treatment protocols. PATIENTS AND METHODS: All our
      acromegalic patients were included (n=48; 27 women). Demographic, hormonal,
      visual and imaging data at diagnosis and during follow-up were recorded, as well
      as the treatments applied. RESULTS: In 73.0% of the patients, acromegaly was due
      to a pituitary macroadenoma. From those under periodic surveillance, 68.2%
      underwent surgery and 36.4% had radiotherapy. At the time of the study 88.6% of
      the patients were receiving medical therapy, 28.2% of them as first-line
      treatment. Applying current criteria, only one patient was cured by surgery.
      Considering normal age and sex-matched concentrations of IGF-I as a control
      criteria, surgery resulted in disease control in 10% of the patients who had
      surgery, while medical treatment controlled the disease in 76.9% (P <0.05). Of
      those who receive medical therapy as first-line treatment, tumour size decreased
      in 45.5%, while in the rest no significant changes were observed during follow
      up. CONCLUSIONS: Not all centres obtain the results reported in the literature in
      terms of disease control and morbidity after surgical treatment of growth hormone
      secreting tumours. It is possible that in some hospitals first-line medical
      treatment should be chosen, unless the patient has visual disturbances, as long
      as it is not clear that partial surgical removal of the tumour significantly
      improves response to medical therapy or reduces its costs.

PMID- 19112391
TI  - Tau protein, phosphorylated tau protein and beta-amyloid42 in the cerebrospinal
      fluid of multiple sclerosis patients.
AB  - OBJECTIVES: The presented study focuses on the importance of measurement of beta
      amyloid42 (Abeta-42) levels, total tau protein, and phosphorylated tau (p-tau)
      protein in the cerebrospinal fluid (CSF) of cerebrospinal multiple sclerosis (MS)
      and clinically isolated syndrome (CIS) which represents an early phase of
      multiple sclerosis. METHODS: A total of 23 patients with clinically isolated
      syndrome and suspected MS were enrolled into the study. Of this number, 14
      patients met the criteria for definitive MS according to McDonald. The control
      group consisted of 40 patients examined for the possibility of organic damage to
      the brain, which was not confirmed. We used method of enzyme immunoanalysis to
      examine concentrations of tau protein, p- tau protein, and beta amyloid42.
      Differences between the respective groups were examined by test statistics. In
      addition, dependence of the total tau protein, p-tau protein, and beta-amyloid42
      levels on demographic variables, diagnosis and duration of disease was examined
      by correlation analysis. Correlation of the concentrations obtained in the
      measurements was evaluated based on the calculated correlation coefficient (r)
      and level of significance (p). RESULTS: Compared to the control group, no
      statistically significant difference was found in the levels of tau protein and p
      tau protein between the CIS group and definitive MS group. A significant increase
      was found only for beta-amyloid42 levels in patients with diagnosed MS vs.
      control group. We demonstrated no correlation between the beta-amyloid42 and tau
      protein levels, p-tau protein and age of patients and duration of disease in
      patients with MS, CIS and the control group. CONCLUSION: Results of our study
      show that use of tau protein, p-tau protein and beta-amyloid42 in the diagnosis
      of multiple sclerosis seems to be non-beneficial. We confirmed no importance for
      the differential diagnosis of an early stage MS.

PMID- 19112392
TI  - Tardive dyskinesia: determinants of temporal dynamics of its emergence.
AB  - BACKGROUND: The second generation antipsychotics (SGA) is considered to have
      contributed to the decrease of the risk of TD in comparison with the first
      generation antipsychotics (FGA). Using the multiple regression analysis, we
      compared the predictive strength of the FGA/SGA distinction with the predictive
      strength of the duration of treatment, patients' age and sex. The difference
      between sedative (sed) and incisive (inc) antipsychotics was added as the fifth
      predictor. METHOD: A cohort of patients treated with antipsychotic drugs for less
      than 5 years and who were free from TD was followed for one year and examined
      regularly by the abnormal involuntary motor scale (AIMS). RESULTS: From a sample
      of 98 patients, 6 patients developed TD after six months. The duration of
      treatment, age and sex of the patients were the main determinants of its
      emergence. The drugs used did not play a statistically significant role. After
      one year, 15 patients developed TD. Age and sex lost their statistically provable
      influence on its emergence. The difference between the treatment with sedative or
      incisive antipsychotics became the variable with the highest statistical
      significance. The relationship of the risk of TD to the FGA/SGA distinction was
      not statistically significant. 14.4% of the variability in the increase of the
      risk of TD during the second half of the one year observational period could be
      explained by the predictors. The stepwise regression showed that both, SG/FG and
      sed/inc distinction remained statistically significant.

PMID- 19112393
TI  - Survivin products in pituitary tumors.
AB  - OBJECTIVES: Survivin is a member of the inhibitor of apoptosis protein family,
      which was recently showed to be expressed by different benign and malignant human
      tumors. Still very little is known about survivin expression in pituitary tumors.
      In spite of the fact that pituitary tumors in histological examination are
      usually benign, in the clinical process a certain number of pituitary adenomas is
      capable of aggressive growth, recurrence and invasion of the surrounding
      structures. The aim of the present study was to assess the presence of survivin
      transcripts and protein in different types of pituitary tumors and to evaluate
      survivin expression levels in invasive and non-invasive pituitary tumors. DESIGN
      AND METHODS: The analyzed material consisted of tumor tissue samples obtained
      during standard neurosurgical removal of the tumor from 23 patients in whom
      acromegaly (n=14), non-functioning pituitary tumor (n=6), prolactinoma (n=2) and
      corticotropinoma (n=1) were diagnosed. As a control of the study normal pituitary
      tissue obtained at autopsy was used. Amplification of survivin gene using
      sequence specific primers and qRT-PCR method and immunohistochemical staining
      with primary polyclonal antibodies against human survivin were performed.
      RESULTS: Our study demonstrated the presence of survivin mRNA in all 23 analyzed
      pituitary tumors. Survivin expression was also observed in normal pituitary, but
      the level of its expression was 6-fold lower than in tumors tissue when studied
      by real time RT-PCR. The difference between the levels of survivin expression in
      invasive and non-invasive tumors was not statistically significant.
      Immunohistochemical analyses revealed the presence of the protein in both normal
      and tumor tissue of pituitary. Immunostaining of tumor tissue was not uniform.
      Survivin was observed mainly in the nuclei of cells collected in clusters. The
      presence of the protein in normal pituitary was restricted to small population of
      cells. CONCLUSIONS: The present study showed that overexpression of survivin is
      characteristic for pituitary tumors. Further analysis of this protein expression
      profile should demonstrate whether survivin might be use as a prognostic marker
      in diagnosis and therapy of pituitary adenomas.

PMID- 19112394
TI  - Should tactile sensation impairment be considered in pharmacotherapy of pervasive
      developmental disorders? A case report.
AB  - It is a case report of improvement of tactile defensiveness after taking
      sertraline in a woman with major depressive disorder and Asperger's syndrome.

PMID- 19112395
TI  - Relation of trophic changes in the central nervous system, measured by the width
      of cordical sulci, to the clinical course of anorexia nervosa (II).
AB  - OBJECTIVES: In patients with anorexia nervosa (AN), computer tomography (CT)
      scanning and/or magnetic resonance imaging (MR) are usually applied to visualise
      trophic changes of the brain, resulting from considerable malnutrition or general
      cachexia of the organism. The goal of the study was an evaluation attempt of the
      degree of trophic changes in the central nervous system (CNS) of girls with AN,
      following CT scanning of the brain, together with an analysis of selected
      clinical and diagnostic parameters, related to the trophic changes in question.
      PATIENTS & METHODS: The study involved fifty-five (55) female patients with AN.
      Following CT of the brain - scanning of the cortical sulci - four (4) groups of
      the patients were identified. The following classification of lesions was
      applied: Group I - width of cortical sulci < 1.5 mm - standard; Group II - the
      presence of cortical sulci of width < 1.5 mm and 1.5-3 mm; Group III - width of
      cortical sulci 1.5-3 mm; Group IV - the presence of cortical sulci of width at
      1.5-3 mm and > 3 mm. We did not observe any patient with AN in whom the width of
      all the cortical sulci was bigger than 3 mm (Group V). In all the groups,
      clinical parameters, as well as routine laboratory tests and selected hormonal
      tests, were analysed. RESULTS: In the performed CT scanning of the head in
      patients with AN, trophic changes in the CNS (as evaluated by the width of
      cortical sulci) were revealed in 67.3% of the patients. Among the studied groups,
      statistically significant differences were found for: body weight loss (BWL), the
      percent of BWL (BWL%), the BWL to disease duration ratio (BWL/time) and
      BWL%/time, serum concentrations of potassium, calcium, glucose, total protein and
      urea, as well as serum concentrations of LH, E2, cortisol, FT3 and FT4. The most
      pronounced disturbances were observed in Group IV, while the least ones - in
      Group I. CONCLUSIONS: In CT scanning of the head, trophic changes in the CNS were
      observed in girls with AN, measured by the width of cortical sulci. The higher
      severity of trophic changes in the CNS was associated with higher BWL/time ratio,
      higher hypercortisolemia, more enhanced hypogonadotrophic hypogonadism, disorders
      in the peripheral metabolism of the thyroid hormones and with the obtained values
      of routine laboratory tests, indicating some tendency towards hypovolemia.

PMID- 19112396
TI  - Schizophrenia in childhood and adolescence.
AB  - Schizophrenia is a disorder characterized by delay in neurodevelopment and by a
      central disorder of recognition (i.e. with generalized cognitive deficit).
      Connectivity impairments in the areas of the social brain and cerebellum are the
      "messenger" of abnormal CNS development in schizophrenia. Processes of neuronal
      reorganization in cortical and subcortical structures, aberrant forms of pruning,
      sprouting, and myelinization may play a major role in the pathogenesis of a
      schizophrenic breakdown. Models of neuroplasticity during adolescence can be
      connected with models of neurodevelopmental vulnerability and models of
      neurotoxicity to form an integrated approach in order to better understand
      premorbid adjustment, onset, and course of schizophrenia. The loss of plasticity
      and aberrant myelinization lead to a deterioration in cognitive functions, social
      dysfunction and, in individuals with specific genetic vulnerability, to
      expression of schizophrenia. This article discusses brain development in relation
      to the diagnosis of schizophrenia and the basic symptoms of childhood
      schizophrenia (with early and very early onset) and of adolescent schizophrenia.

PMID- 19112397
TI  - Pregnancy coexisting with a uterine abscess in a double uterus: a case report and
      review of literature.
AB  - A 20 year old primigravida with a double uterus was admitted with a viable fetus
      in the right uterus and pus oozing from the left one. Management consisted of a
      regimen of intravenous antibiotics and intravaginal antibiotic tablets. Tocolysis
      was used to arrest imminent preterm labor. In the course of pregnancy IUGR was
      diagnosed. At 38 weeks of pregnancy a SGA baby boy of 2,440 g was delivered by
      cesarean section. The mother and the baby were discharged from the hospital in
      good general condition.

PMID- 19112398
TI  - Gynecological issues after organ transplantation.
AB  - Organ transplantation has become universally accepted treatment of end-stage
      organ failure. The main problem focuses on preventing the graft from rejection
      with the use of immunosuppressive agents. High incidence of infection is the most
      frequent adverse effect of immunosuppressive therapy. Symptoms of inflammation
      are often reduced in immunosuppressed patients. All invasive diagnostic and
      therapeutic procedures should be associated with the increase in dose of steroids
      and prophylactic antibiotics. Ovarian and menstrual function is usually restored
      in transplanted women. Function of the hypothalamus-pituitary-ovary axis in
      transplanted women is believed to be normal. Most common abnormal uterine
      bleeding in graft recipient are: prolonged and profuse menstruation and inter
      menstrual bleeding or spotting. Among the underlying diseases are lesions of the
      uterus (fibroids, endometrial or cervical polyps), infections of sex organs or
      hormonal disturbances. Higher rate of endometrial hyperplasia (without atypia) is
      reported in renal graft recipients. Organ transplantation results in the restored
      fertility thus effective family planning method is necessary in women of
      reproductive age who do not want to conceive. Vaginal diaphragms are not advised
      and intrauterine device are contradicted. Observational studies indicate for
      safety and high rate of acceptance of oral and transdermal hormonal contraception
      in transplanted women. Over ten-year experiences of HRT administration in graft
      recipient have proved the benefits of the therapy. Patients after organ
      transplantation have three to four-fold increased incidence of malignancy
      compared with general population. All transplant women must undergo regular
      gynecological screening for premalignant and malignant lesions of sex organs and
      breast.

PMID- 19112399
TI  - Preemptive levetiracetam decreases postoperative pain in rats.
AB  - OBJECTIVES: Preemptive versus therapeutic effects of levetiracetam were
      investigated in a model of postoperative incisional pain in rats. METHODS:
      Levetiracetam (250, 500, and 1000 mg/kg intraperitoneal (i.p.) or morphine (5
      mg/kg i.p.) was administered either 1 h before (preemptive administration) or 1 h
      after (therapeutic administration) incisional surgery to the hind paw of rats.
      The effects of levetiracetam were evaluated based on thermal hyperalgesia
      measured by the plantar test. RESULTS: All preoperatively treated levetiracetam
      groups showed a significant, dose dependent, increase in paw withdrawal latency.
      However, post-incisional administration of levetiracetam produced no
      antihyperalgesic effect at any dose or at any time. In contrast, post-incisional
      administration of morphine reduced thermal hyperalgesia, while preemptive
      administration of morphine did not produce any significant antihyperalgesic
      effects. CONCLUSION: The present results suggest that levetiracetam might possess
      preemptive analgesic activity.

PMID- 19112400
TI  - Polymorphism in genes of growth hormone receptor (GHR) and insulin-like growth
      factor-1 (IGF1) and its association with both the IGF1 expression in liver and
      its level in blood in Polish Holstein-Friesian cattle.
AB  - BACKGROUND: Polymorphisms in the bovine ghr and igf1 genes. Ghr and igf1 genes
      have been associated with milk and meat production of cattle. However, the
      molecular and physiological mechanisms underlying such associations are unknown.
      The objective of this study was to examine the effects of polymorphisms in 5'
      regions of the bovine ghr and igf1 genes on the igf1 gene expression in the liver
      and on the level of IGF1 in blood of Polish Holstein-Friesian cattle. METHODS:
      Individual and combined effects of single nucleotide polymorphisms (SNPs) in the
      5'noncoding regions of the bovine igf1 and ghr genes on the IGF1 level in blood
      and igf1 gene expression in liver were examined. One SNP in the igf1 gene and
      four SNPs in the ghr gene were analyzed. IGF1 level in blood was measured by
      radioimmunoassay (RIA) in 211 heifers and bulls of Polish Holstein-Friesian
      cattle (of Black-and-White type). The igf1 gene expression was measured in livers
      of bulls carrying different igf1 and ghr genotypes (from three to nine animals
      per genotype) using real-time reverse transcription-PCR methods with the gapdh
      gene as a reference. RESULTS: We showed that C/T transition in the promoter
      region of the igf1 gene influences the gene expression; relative igf1 expression
      was higher for animals with the CC genotype than for those with the TT and CT
      genotypes. TESS analysis showed that C/T transition in the igf1 gene co-localizes
      with the NF1 transcription factor binding site. Also, the ghr genotype appeared
      to significantly influence the igf1 gene expression in the liver, and we found
      the highest expression for the genotypes: RFLP-AluI (AT), RFLP-Fnu4HI(CC), and
      RFLP-NsiI(GA), and for the combined ghr genotype: AluI(AT)/ Fnu4HI(CC)/NsiI(GA).
      We discovered a significant association between the igf1 genotype and the IGF1
      blood level. The highest IGF1 content in blood serum was found in CC genotype
      animals (1024 ng/ml) vs 698 ng/m and 859 ng/min in the TT and CT igf1 genotypes,
      respectively. Moreover, we noticed significant differences between ghr genotypes.
      The highest blood levels of IGF1 were for the animals carrying the ghr genotypes:
      RFLP-AluI(AA), RFLP-Fnu4HI(CC), and RFLP-NsiI(AG). Ghr haplotypes also
      significantly affected the IGF1 blood level. Animals of the combined ghr
      genotypes AluI(AA)/AccI(CC)/Fnu4HI(CC)/NsiI(AG) and AluI(AA)/AccI(CT)/Fnu4HI
      (CC)/ NsiI(AG) had a higher IGF1 concentration in blood than other genotype
      carriers. CONCLUSIONS: The present results indicate that the effects of
      polymorphism in the igf1 and ghr genes on cattle milk or meat production traits
      could be at least partially mediated through their effects on the igf1 gene
      expression in the liver and the IGF1 level in blood.

PMID- 19112401
TI  - Normalization of leaky gut in chronic fatigue syndrome (CFS) is accompanied by a
      clinical improvement: effects of age, duration of illness and the translocation
      of LPS from gram-negative bacteria.
AB  - BACKGROUND: There is now evidence that an increased translocation of LPS from
      gram negative bacteria with subsequent gut-derived inflammation, i.e. induction
      of systemic inflammation and oxidative & nitrosative stress (IO&NS), is a new
      pathway in chronic fatigue syndrome (CFS). METHODS: The present study examines
      the serum concentrations of IgA and IgM to LPS of gram-negative enterobacteria,
      i.e. Hafnia Alvei; Pseudomonas Aeruginosa, Morganella Morganii, Pseudomonas
      Putida, Citrobacter Koseri, and Klebsielle Pneumoniae in CFS patients both before
      and after intake of natural anti-inflammatory and anti-oxidative substances
      (NAIOSs), such as glutamine, N-acetyl cysteine and zinc, in conjunction with a
      leaky gut diet during 10-14 months. We measured the above immune variables as
      well as the Fibromyalgia and Chronic Fatigue Syndrome Rating Scale in 41 patients
      with CFS before and 10-14 months after intake of NAIOSs. RESULTS: Subchronic
      intake of those NAIOSs significantly attenuates the initially increased IgA and
      IgM responses to LPS of gram negative bacteria. Up to 24 patients showed a
      significant clinical improvement or remission 10-14 months after intake of
      NAIOSs. A good clinical response is significantly predicted by attenuated IgA and
      IgM responses to LPS, the younger age of the patients, and a shorter duration of
      illness (< 5 years). DISCUSSION: The results show that normalization of the IgA
      and IgM responses to translocated LPS may predict clinical outcome in CFS. The
      results support the view that a weakened tight junction barrier with subsequent
      gut-derived inflammation is a novel pathway in CFS and that it is a new target
      for drug development in CFS. Meanwhile, CFS patients with leaky gut can be
      treated with specific NAIOSs and a leaky gut diet.

PMID- 19112402
TI  - Necrotizing enterocolitis in children with low birth-weight induced with
      mucormycose strains.
AB  - BACKGROUND: The nosocomial occurrence of mycotic infections negatively affects
      results of the neonatal care in newborns in the sense of their increased
      mortality and morbidity. AIM: The communication presented here is focused on an
      analysis of predisposing factors and clinical patterns of infections induced with
      mucormycosis strains. The authors provided an analysis of six case reports
      concerning newborns that died in association with nosocomial infections, where
      mucormycosis strains were microbiologically and microscopically detected in
      autopsy. RESULTS: The newborns in the group considered died due to general
      metabolic breakdown induced by peritonitis based on the large intestine
      perforation - enterocolitis. The predisposing factors include low birth-weight,
      asphyxia after the delivery, catheterization of umbilical veins and v. cava
      inferior and introduction of the endotracheal ventilation. Nosocomial nature of
      the infection propagation is suggested by a delayed onset of manifestations after
      the delivery. CONCLUSION: The authors point out the possibility of the
      origination of nosocomial infection induced with mucormycotic strains. Thus, they
      recommend adhering to a strict anti-epidemic regimen at neonatal departments with
      a particular emphasis put on consequent prohibiting of the storage and use of
      food at the departments. They emphasize the fact that the most frequent clinical
      pattern induced with mucormycotic strains in newborns with low birth-weight is
      necrotizing enterocolitis. They also stress the fact that the final diagnosis of
      the infection is most typically established based on the histological examination
      only.

PMID- 19112403
TI  - Impact of antiovarian antibodies (AOA) on ovarian responsiveness in vitro
      fertilization and embryo transfer.
AB  - OBJECTIVE: This study was to investigate the effects of antiovarian antibodies
      (AOA) on ovarian responsiveness in vitro fertilization and embryo transfer
      (IVF/ET). METHODS: 233 infertility women younger than 36 years undergone IVF/ET
      because of single salpingemphraxis were attended in the study, whose fast blood
      was taken to detect serum AOA by ELISA. Among them there were 35 women with serum
      AOA positive composed the study group and the other with serum AOA negative
      composed the control. Ovarian volume, antral follicle number, basal FSH,
      gonadotropin dosage and recollected oocytes were compared between the 2 groups.
      RESULT(S): There's no difference in ovarian volume between serum AOA positive
      group with negative group, P>0.05. The number of antral follicles was less and
      basal FSH was higher in AOA positive group than in control, P<0.05; what's more,
      the ampoules of gonadotrophin consumed in AOA positive group exceed significantly
      in control, and less recollected oocytes in AOA positive group than in control,
      P<0.01. Of the 233 infertility women, the serum AOA positive rate was 73.08% in
      the women who got less than 5 recollected oocytes, significantly higher than the
      other women in the study, P<0.01. CONCLUSION(S): The existing of anti-ovarian
      antibodies had suppressive effects on the ovarian responsiveness in ovarian
      stimulation in IVF/ET cycle and on ovarian function. AOA should be detected
      before IVF/ET to evaluate ovarian responsiveness and further treatment seems
      necessary.

PMID- 19112404
TI  - Health related quality of life of children and adolescents with type 1 diabetes.
AB  - Type 1 diabetes mellitus is a chronic health condition which affects
      approximately 750 thousand diabetics in the Czech Republic out of whom 3300 are
      children at the age of 8-18 years. The effects of illness and treatment go beyond
      medical control therefore evaluation of quality of life (QOL) is vital for
      children and adolescents with diabetes in order to examine how diabetes and its
      complicated and demanding treatment regimen affects their various life domains -
      family relationships, school, social activities, etc. Health related quality of
      life has been recognized as an important pediatric outcome measure in the past
      years and therefore health related quality of life of these children and
      adolescents was evaluated. The Pediatric Quality of Life Inventory 4.0 (PedsQL)
      and PedsQL 3.0 Module Diabetes were translated into the Czech language and
      administered to 79 children with diabetes and 79 parents. The objective of this
      study was to examine general and health related quality of life of children with
      diabetes at the age of 8-18. Results showed, that children endorse greater QOL in
      both general and diabetes related scales compared to their parents. Also, the
      concordance in reports of parents and children of QOL in children was variable.
      With regard to the aim of the research to determine whether QOL outcomes are
      predicted by duration of diabetes, results show that the duration of diabetes is
      a significant predictor of QOL in children. These results of QOL in children in
      the Czech Republic are then compared with the outcomes available from abroad.

PMID- 19112405
TI  - Fluorescence and inmunohistological detection of estrogen receptors in dog testis
      and epidydimis after oral coumestrol administration.
AB  - INTRODUCTION: Estrogens are well recognized as important hormones in male
      reproduction and act as ligands to alpha and beta estrogen receptors. Both
      estrogen receptors could interact with estrogen-mimicking compounds such as the
      fluorescent phytoestrogen coumestrol, which acts both in an agonist or antagonist
      fashion. OBJECTIVE: To investigate the presence of Coumestrol-Estrogen Receptor
      complexes by fluorescence in testis and epididymis, its effect in the ER
      expression by immunostain in the same tissues and the effect of this binding in
      the testis histological characteristics. DESIGN: Adult healthy and sexually
      active dogs were assigned to either the experimental or control group .Coumestrol
      impregnated dog biscuits were given to each animal from the experimental group
      once a week for a 4 week period. The control group received a biscuit with no
      Coumestrol, also once a week and for the same period. Testis morphology, ER
      immunodetection, and coumestrol-receptor binding were evaluated. SETTING: The
      experiment was done in the facilities of the Mexico City canine shelter. Animals
      were caged individually with food and water ad libitum and having at least two
      daily hours for exercise. RESULTS: Morphological alterations in testis after oral
      administration of coumestrol were detected. The main alterations include
      decreased germinal epithelium in tubule, and the loss of a continuous
      proliferation and differentiation gamete layer. Fluorescence signals in testis
      interstitial Leydig cells and epididymus indicating ER-coumestrol complexes were
      detected at the same points to those Immunohystochemically detected ER.
      CONCLUSIONS: Coumestrol administration induces testis alterations and coumestrol
      ER complexes can be co-localized by binding-enhanced fluorescence and
      immunoprecipitation.

PMID- 19112406
TI  - Fetal pain.
AB  - The fetus reacts to nociceptive stimulations through different motor, autonomic,
      vegetative, hormonal, and metabolic changes relatively early in the gestation
      period. With respect to the fact that the modulatory system does not yet exist,
      the first reactions are purely reflexive and without connection to the type of
      stimulus. While the fetal nervous system is able to react through protective
      reflexes to potentially harmful stimuli, there is no accurate evidence concerning
      pain sensations in this early period. Cortical processes occur only after
      thalamocortical connections and pathways have been completed at the 26th
      gestational week. Harmful (painful) stimuli, especially in fetuses have an
      adverse effect on the development of humans regardless of the processes in brain.
      Moreover, pain activates a number of subcortical mechanisms and a wide spectrum
      of stress responses influence the maturation of thalamocortical pathways and
      other cortical activation which are very important in pain processing.

PMID- 19112407
TI  - Exogenous galanin regulates capsaicin-evoked substance P release from primary
      cultured dorsal root ganglion neurons.
AB  - OBJECTIVES: To determine the effect of exogenous galanin on capsaicin-evoked
      substance P (SP) release from primary cultured embryonic rat dorsal root ganglion
      (DRG) neurons. METHODS: DRG was dissected out from embryonic 15-day-old Wistar
      rat and cultured as dissociated cells for 2 days then exposed to galanin (1
      nmol/L, 10 nmol/L, 100 nmol/L). After 4 days incubation with exogenous galanin,
      the levels of mRNAs for SP and vanilloid receptor 1 (VR1) and protein for VR1
      were estimated by RT-PCR and Western blot, respectively. Basal SP release and
      capsaicin-evoked SP release levels were measured by radioimmunoassay (RIA).
      RESULTS: The amount of VR1 mRNA and VR1 protein expression and capsaicin-evoked
      SP release in cultured DRG neurons increased significantly after incubation with
      exogenous galanin compared with control DRG neurons at the same time point,
      whereas the amount of SP mRNA and basal SP release were not affected after
      incubation with exogenous galanin. DISCUSSION: Exogenous galanin may promote
      capsaicin-evoked SP release from primary cultured DRG neurons. The elevation of
      the levels of VR1 mRNA and VR1 protein induced by exogenous galanin implicated
      that VR1 may be involved in the mechanisms of SP release evoked by capsaicin.

PMID- 19112408
TI  - Enhancement of neutral endopeptidase activity in SK-N-SH cells by ginsenoside
      Rb1.
AB  - OBJECTIVES: To investigate the effect of ginsenosides Rb1 and Rg1 on Neprilysin
      (NEP) activity in SK-N-SH cells, and probe the underlying mechanism. METHODS: The
      effects of ginsenosides Rb1 and Rg1 on NEP activity were analyzed by NEP
      peptidase assay. Western blot was used to determine NEP gene expression at
      translational level, and RT-PCR was also performed to detect NEP gene expression
      at transcriptional level. RESULTS: NEP peptidase assay indicated that ginsenoside
      Rb1 can improve the activity of NEP, and RT-PCR and western blot results showed
      that the enhancement of NEP activity by ginsenoside Rb1 was due to enhancing NEP
      gene expression, while Rg1 did not have this effect. CONCLUSION: Our studies
      showed that ginsenoside Rb1 can enhance NEP activity by upregulating NEP gene
      expression. Our findings might offer a pharmacological explanation for the use of
      ginseng in traditional medicine.

PMID- 19112409
TI  - Effectiveness of speech analysis by self-organizing maps in children with
      developmental language disorders.
AB  - At present, more and more researchers are applying tested mathematical
      engineering methods into different domains of life. One of these areas is helping
      people with different forms of disabilities. Research in this area is focused on
      searching for the relation between clinical and electrophysiological symptoms of
      children with developmental dysphasia. Sleep EEG and speech analyses are the
      primary areas under discussion, while the finding of methods acceptable for
      improvement of the diagnosis and determination of therapeutic procedures is the
      research topic. It is possible to reduce fundamentally, or to cure optimally
      these disorders in advanced diagnosis. Therefore it is important to search for
      new methods and to combine what has been used separately till now.

PMID- 19112410
TI  - Effect of Nogo-A gene inhibition on dopamine release in PC12 cells.
AB  - OBJECTIVES: Reticulon proteins, which are localized in the endoplasmic reticulum,
      have recently been shown to be involved in hormone secretion, in particular RTN1
      and RTN3. The aim of the present study was to examine the effects of Nogo-A gene
      expression knockdown by RNA interference (RNAi) on dopamine release in PC12
      cells. METHODS: A small hairpin RNA (shRNA) eukaryotic expression vector,
      targeting the Nogo-A gene, was constructed and transfected into cultured PC12
      cells by lipofecamine2000. Inhibition of Nogo-A gene expression was detected by
      semi-quantitative reverse transcription PCR and Western blot analysis. Following
      transfection, dopamine release was detected by high performance liquid
      chromatography. RESULTS: The pGenesil-1-Nogo-A-2 plasmid was identified by gene
      sequencing. After transfection of the recombinant vector in PC12 cells, Nogo-A
      gene expression was significantly inhibited (p<0.01). Compared with the empty
      vector control group, dopamine release significantly decreased within 48 hours
      after transfection. CONCLUSION: Results from this study suggest that Nogo-A might
      be involved in the mechanism of DA release in PC12 cells.

PMID- 19112411
TI  - Duration of untreated psychosis and it's effect on the symptomatic recovery in
      schizophrenia - preliminary results.
AB  - OBJECTIVES: A long duration of untreated psychosis (DUP) is known to be
      associated with a poorer prognosis and with worse symptomatic and functional
      outcome. The aim of the study was to test the hypothesis that early detection and
      treatment with antipsychotics in the prodromal phase of the illness improves the
      outcome; to compare short and long-term outcome in patients with DUP longer than
      1 year (group 1) with patients that were treated already in the prodromal phase
      of the disease (group 0). DESIGN AND SETTING: Eighty-seven patients with
      schizophrenia were included to the retrospective study, 37 patients to group 0
      and 50 patients to group 1. The course and outcome of the disease was studied in
      the two groups. The severity of schizophrenia was evaluated by measuring several
      outcome parameters. The symptom severity was evaluated using a check list
      developed from CAARMS inventory; the average daily dose of antipsychotics was
      calculated as well as the number and duration of hospital admissions. Groups were
      compared during the acute psychosis of first episode (t1) and at the conclusion
      of the study (t2). RESULTS: More symptoms of greater intensity were present
      during the first and second evaluations in group 1 as compared to group 0
      patients. The patients in group 0 needed lower dosages of antipsychotics even
      several years after treatment had been initiated. This effect persisted until the
      final evaluation; 11% were without antipsychotics at the conclusion of the study.
      Patients in group 1 were hospitalized more frequently; they needed more
      hospitalizations and these were of longer duration. Only 38% of patients in group
      0 were treated in the hospital, 27% were hospitalized only once. CONCLUSIONS:
      Better outcome can be achieved with early antipsychotic treatment. Patients with
      long DUP differ from patients who were treated already in the prodromal phase in
      several outcome measures.

PMID- 19112412
TI  - Dipeptide "alaptide" prevented impairments in spontaneous behavior produced with
      trimethyltin in male rats.
AB  - OBJECTIVES: On the animal model of trimethyltin (TMT) induced behavioral deficits
      the effect of chronic treatment with spirocyclic dipeptide cyclo/alanyl-l-amino-l
      cyclopentane-carbonyl (alaptide, AL) was evaluated in adult male rats. METHODS:
      Changes in the spontaneous behavioral repertoire were investigated in the open
      field test on Day 21 (Session 1) and Day 28 (Session 2) after a single oral TMT
      administration. RESULTS: In Experiment 1, rats given the highest TMT dose (7.5
      mg/kg) exhibited significantly increased total number of behavioral patterns, the
      floor sniffing being the most frequent pattern. While the medium TMT dose (5
      mg/kg) had a similar effect only in Session 1, the lowest TMT dose (2.5 mg/kg)
      was entirely ineffective. In Experiment 2, an explicit beneficial influence of
      both AL doses (5 and 10 mg/kg) given for 10 days before and 10 days after TMT
      (7.5 mg/kg) on the spontaneous behavior repertoire was observed in both Session 1
      and Session 2. The total number of patterns and the time spent in individual
      patterns of AL+TMT treated animals did not differ from the controls and those
      given AL alone. CONCLUSION: We conclude that sufficiently long AL treatment
      interfered with deleterious effects of TMT and forestalled changes in the
      structure and timing of spontaneous behavioral patterns. Thus, AL can be
      designated as a substance having "neuroprotective" effects.

PMID- 19112413
TI  - Development of real-time PCR assays in the study of gonadotropin subunits,
      follistatin and prolactin genes expression in the porcine anterior pituitary
      during the preovulatory period.
AB  - OBJECTIVES: Neural control of the anterior pituitary function consists of the
      interplay of neuropeptides action, gonadal steroid hormones and many other
      factors. The physiological effect of this regulatory action is the release and
      synthesis of protein hormones in the precise time and quantity. The main factor
      responsible for the gonadotropins release and synthesis is the gonadotropin
      releasing hormone (GnRH). We must still study the modulation of the synthesis of
      the gonadotropins subunits - LHbeta, FSHbeta and alpha subunit by different forms
      of GnRH and by its analogs, in order to better understand the regulation of
      gonadotropin release and synthesis. THE AIM of this study was to develop real
      time PCR assays of five candidate reference genes for normalization purposes in
      order to quantify target transcripts in anterior pituitary cells during the
      preovulatory period. Moreover, we focused on the influence of GnRH receptor
      antagonist (antide) treatment on mRNA expression levels of GPalpha, LHbeta,
      FSHbeta, FST(follistatin) and PRL(prolactin) genes in these cells. MATERIAL AND
      METHODS: Anterior pituitary cells were obtained from pituitary glands of four
      mature pigs at the preovulatory phase. Cells were incubated with or without
      antide and relative mRNA level of target genes was measured using the Applied
      Biosystems 7500 Real Time System. For an exact comparison of mRNA quantity, the
      stability of five reference genes, ACTB, B2M, GAPDH, RPL1, and TOP2B was
      evaluated to choose the most appropriate reference gene for qRT-PCR normalization
      in the pituitary cells. Expression stability of reference genes was calculated
      using the geNorm application. The developed method of PCR assay was applied to
      study gene expression in pig pituitary cells in short culture. RESULTS: The most
      stably expressed genes in the pituitary cells were GAPDH and TOP2B. The
      expression of ACTB, B2M and RPL1 appeared to be highly unstable. After
      normalization to the GAPDH/TOP2B, results showed that the mRNA expression of the
      FSHbeta gene was highest in comparison with LHbeta, GPalpha, FST and PRL genes
      (p<0.005). Pre-treatment of cells by the antide resulted in lower mRNA expression
      of these genes, while FSHbeta mRNA had a significantly lower expression (p<0.05)
      in comparison with control. CONCLUSIONS: Real-time PCR analysis of the expression
      of LHbeta, FSHbeta, alpha subunit, follistatin and prolactin genes in porcine
      anterior pituitary cells during the preovulatory period is suitable for the study
      of modulatory action of metal complexes with GnRH on the expression of these
      genes.

PMID- 19112414
TI  - Consciousness and general anaesthesia: a recent view.
AB  - An explanation of consciousness is one of the major unsolved problems of modern
      science. The modern view of consciousness arose in the nineteenth century; the
      view presumed that mental activity correlates with distinct physical states. Is
      the problem of consciousness real? Crick and Koch made a tentative assumption
      that all different aspects of consciousness (pain, seeing, thinking, emotion,
      self-consciousness) are connected by a basic common mechanism. The next step
      towards understanding involved the neuronal theories of consciousness (correlates
      of consciousness), often referred as the NNC (neural correlates of
      consciousness). Many neuroscientists presume that consciousness must have a
      neuronal correlate. The neuroscience of anaesthesia can be defined as studying
      the effect of anaesthetic agents on consciousness and the preconsciousness brain
      mechanisms of cognitive function. Some of these mechanisms, such as recognition
      of the novel stimuli, are still present in deep anaesthesia, during continuous
      suppression. Anaesthesia is not "an all or nothing" phenomenon and consciousness
      awareness with explicit memory represents only one part of the spectrum of
      cognitive functions. The introduction of safe general anaesthesia represents one
      of the most important, although under-appreciated, advances in modern surgery.
      There is some difficulty in defining the term "consciousness" in relation to the
      anaesthetic state. The difference in brain activity between those under
      anaesthesia and those not under any such influence.

PMID- 19112415
TI  - Concurrent occurrence of multiple sclerosis and primary CNS lymphoma: a case
      report.
AB  - We present the patient with the diagnosis of multiple sclerosis (MS), relapsing
      remitting form with long lasting remission. Unexpectedly, this patient presented
      dramatical clinical deterioration and revealed clinical symptoms such as
      bradypsychia, cognitive symptoms, central vestibulare syndrome, spastic
      quadruparesis. Clinical findings suggested secondary progressive MS, but MRI
      called in question this diagnosis. The MRI appearance suggested, that MS had been
      complicated by a different brain pathological lesion, and the brain biopsy was
      indicated. A histological examination confirmed primary CNS lymphoma (PCNSL).
      This case exemplifies important aspects of clinical neurology. A re-evaluation of
      the diagnosis of MS should always be performed in a patient when new symptoms are
      presented that are unusual or could be due to other pathological processes. MRI
      offers the highly sensitive way to detect the coexistence of MS and other brain
      disease. Primary goal of imaging modalities is differential diagnosis between
      demyelinating diseases, such as MS and other brain lesions. Advanced focus demand
      contrast- enhancing and mass- effect lesions. It is important to realize, that
      contrast-enhancement and brain edema may be mitigated by treatment with
      corticosteroids. In some cases a brain biopsy is needed.

PMID- 19112416
TI  - Complete objective response to biological therapy of plurifocal breast carcinoma.
AB  - In this case presentation, a woman with breast carcinoma who chose to try Prof.
      L. DiBella's biological therapy (MDB), was found, after seven months, to have a
      50% reduction in objective measures of her carcinoma and was totally cured after
      14 months. The patient's recovery extended to bilateral axillary adenopathies,
      and took place without the toxicity normally associated with cancer treatment.
      MDB entails the use of anti-proliferative molecules such as somatostatine,
      prolactin, and estrogen inhibitors, along with differentiating and apoptotic
      molecules such as melatonin, retinoids, vitamins C, D3, and E, calcium, and amino
      sugars, combined with minimal doses of chemotherapy. The hemato-chemical exams
      showed no damage, with a progressive reduction of prolactin, estradiol, IGF1, and
      maintenance of low levels of GH. The achievement of objective results, without
      toxicity, in this case, proves the effectiveness of this therapy and confirms the
      positive results already published on the use of MDB for Low-Grade NHL, and
      pulmonary carcinomas in the 3rd and 4th stages. MDB, without the need for either
      hospitalization or day hospitalization, without toxicity, and without even
      minimally reducing the patient's daily work routine, allowed the patient to avoid
      surgical trauma and the significant collateral effects of chemo- and
      radiotherapy. Timely use of MDB as the first line therapy, in a patient which had
      not been debilitated by the mutagenic, toxic, and immuno-depressive effects of
      chemo- and radiotherapy, contributed greatly to the final outcome. We feel it is
      useful to highlight this case in an effort to stimulate interest and further
      study into the oncological potential of MDB biological and receptor therapy.

PMID- 19112417
TI  - Clinical characteristics of 226 college-going female migraineurs in Lahore,
      Pakistan - putting ICHD-2 to the road test.
AB  - The International Headache Society (IHS) criteria-based questionnaires were given
      to 647 college-going females (faculty and students) of selected universities in
      Lahore, Pakistan. Forty five (7%) were diagnosed with Migraine with Aura (MWA),
      181 (28%) with Migraine without Aura (MWOA) and 421 (65%) as NMH (non-migrainous
      headache). We found 'Photophobia and Phonophobia' as the most common headache
      associated symptoms, and 'Stress' and lack of sleep' as the most commonly
      reported triggers of MWA (44%) and MWOA (38%). Most common headache management
      practice amongst migraineurs was 'sleep' [MWA (35%) and MWOA (39%)]. This is the
      first paper which elucidates the symptomatology, risk factors and treatment
      modalities of migraineurs in Pakistan.

PMID- 19112418
TI  - Chronic isolation of adult rats decreases gene expression of catecholamine
      biosynthetic enzymes in adrenal medulla.
AB  - OBJECTIVE: Isolation of adult animals represents a form of psychsocial stress
      that produces sympatho-adrenomedullar activation. The aim of this work was to
      investigate the changes in gene expression and protein levels of catecholamine
      biosynthetic enzymes: tyrosine hydroxylase (TH), dopamine-beta-hydroxylase (DBH)
      and phenylethanolamine N-methyltransferase (PNMT) in the adrenal medulla of naive
      control and chronically (12 weeks) socially isolated adult Wistar rat males and
      the response of these animals to additional immobilization stress (2 h). METHODS:
      TH, DBH and PNMT mRNA levels were quantified by quantitative real-time RT-PCR
      (qRT-PCR). TH, DBH and PNMT immunoproteins were assayed by Western Blot. RESULTS:
      In chronically isolated rats, gene expression levels of catecholamine
      biosynthetic enzymes in the adrenal medulla were decreased, but only TH mRNA was
      significantly decreased. However, protein levels of TH, DBH and PNMT of these
      animals were elevated by 55%, 20% and 18%, respectively, in relation to the
      corresponding control. Naive control and chronically socially isolated rats
      exposed to additional 2-h-immobilization showed increased gene expression of the
      examined enzymes, the increase being greater in socially isolated rats as
      compared to the controls. Additional immobilization of naive controls did not
      affect TH, DBH and PNMT protein levels. In contrast, this stress produced
      increased TH, DBH and PNMT protein levels in long-term socially isolated rats.
      CONCLUSION: We can conclude that psychosocial stress expressed a differential
      influence on gene expression and protein levels of catecholamine biosynthetic
      enzymes in the adrenal medulla of adult rats. The results indicate a possible
      adaptation of catecholamine-synthesizing system at the level of TH gene
      expression in adrenal medulla of chronically isolated animals.

PMID- 19112419
TI  - A generalized theory of carcinogenesis due to chronodisruption.
AB  - For two decades, research has been suggested and conducted into the causation and
      development of cancers in seemingly diverse and unrelated populations such as
      blind individuals, shift-workers, flight personnel, Arctic residents and subsets
      of sleepers. One common denominator of these investigations is "melatonin".
      Another common denominator is that all these studies implicitly pursued the
      validity of the so-called "melatonin hypothesis", of a corollary and of
      associated predictions which can be united in our proposed theory of
      "carcinogenesis due to chronodisruption". The new theory suggests that the
      various predictions investigated between 1987 and 2008 represent different
      aspects of the same problem. Indeed, abundant experimental evidence supports the
      notion that the final common cause of many cases of cancer may be what has been
      termed chronodisruption (CD), a relevant disturbance of the temporal organization
      or order of physiology, endocrinology, metabolism and behaviour. While melatonin
      as a key time messenger and time keeper can be a marker of CD, it is probably
      only partially related to the differential cancer occurrence apparent in
      individuals who chronically or frequently experience an excess or deficit of
      chronodisruption.

PMID- 19112420
TI  - A case of relapsed autoimmune hypothalamitis successfully treated with
      methylprednisolone and azathioprine.
AB  - Autoimmune hypothalamitis is a rare autoimmune neuroendocirne disease. A case of
      a 70-year-old female with autoimmune hypothalamitis was reported. The chief
      clinical characteristics were diabetes insipidus and adenopituitary function
      deficiency. Cranial magnetic resonance imaging (MRI) scan indicated a mass in the
      hypothalamus. The diagnosis of autoimmune hypothalamitis was presumed. After
      treatment with prednisone, there was a marked reduction in the mass and the
      hypothalamus-adenopituitary function partially improved. However, after
      glucocorticoid therapy was withdrawn, the hypothalamic lesion relapsed
      progressively. High dose methylprednisolone pulse therapy (HDMPT) in combination
      with azathioprine was initiated thereafter. During follow-up, MRI scan indicated
      the lesion shrank strikingly, and the patient's clinical condition improved as
      well. In view of the good response of the hypothalamic lesion to glucocorticoid
      and immunodepressant, the putative diagnosis of autoimmune hypothalamitis was
      confirmed. This case report suggested that HDMPT in combination with azathioprine
      therapy might be an effective trial for autoimmune hypothalamitis treatment.

PMID- 19112421
TI  - Oral cancer: risk factors, prevention and diagnostic.
AB  - Although oral cancer is rare and attracts little attention, it ranks 12th among
      all cancers and constitutes the most life threatening of all dental conditions.
      The aetiology of oral cancer is multi-factorial and like other types of cancer,
      the key to decreasing the suffering of patients and increasing their survival
      rate is early detection. The global increase in frequency and mortality of oral
      cancer has intensified current research efforts in the field of prevention and
      early detection of this disease. Therefore, scientists have been searching for
      alternative approaches to biopsy. A number of molecular-based diagnostic markers
      have been used to detect the presence of oral cancer with varying degrees of
      sensitivity and specificity. In this paper, incidence, mortality, risk factors,
      prevention, and diagnostic of oral cancer have been reviewed.

PMID- 19112423
TI  - Analysis of growth kinetics and proliferative heterogeneity of Lewis lung
      carcinoma cells growing as unfed culture.
AB  - AIM: To analyze the growth kinetics and proliferative heterogeneity of Lewis lung
      carcinoma (LLC) cells during their growth in monolayer for 5 days without
      replacement of culture medium (unfed culture). METHODS: Cell biology methods,
      sandwich enzyme-linked immunosorbent assay for vascular endothelial growth factor
      (VEGF) detection (ELISA), enzymatic glucose-oxidase method for glucose
      measurements, mathematical modeling. RESULTS: Created mathematical model showed
      good fit to experimental data; that allowed to determine kinetic (model)
      parameters of LLC cells and predict the changes in number of proliferating and
      quiescent cells (proliferative heterogeneity) during their growth. It was shown
      that growth kinetics of viable LLC cells possesses non-monotonous character -
      during first three days of growth the number of cells raised exponentially, with
      following decrease after the maximal level was achieved. At the same time the
      decrease of number of viable cells/increase of number of dead cells has been
      observed upon complete depletion of culture medium by glucose content. Glucose
      dependence of cell transition rate from proliferation to resting state predicted
      by mathematical model possessed a pronounced two-phase character. At a wide range
      of relatively high glucose concentrations (> 1.0 mg/ml) the transition rate was
      close to zero. At concentrations lower than 0.7 mg/ml, the rate of transition
      swiftly increased resulting in sharp change in cellular composition. At an
      interval from 70 to 90 h, practically all proliferating cells transited to a
      resting state. The rate of quiescent cell death was relatively low, and this was
      in part caused by too low level of glucose consumption compared to proliferating
      cells. It was shown that during LLC cells growth VEGF production rate decreased
      monotonously in spite of the fact that the level of VEGF in incubation medium
      increased monotonously. Observed monotonous decrease of VEGF production rate
      could not be explained by VEGF degradation in incubation medium (our results
      displayed the stability of VEGF molecule during investigations). CONCLUSIONS:
      Weak dependence of cell transition rate from proliferating to resting state from
      glucose level (> 0.7 mg/ml) and low rate of cell death provided slow decrease of
      the pool of quiescent cells in the population, thus significantly increasing
      their chance to survive upon nutritional deficiency.

PMID- 19112422
TI  - Effect of trichostatin a on viability and microRNA expression in human pancreatic
      cancer cell line BxPC-3.
AB  - AIM: To investigate the influence of trichostatin A (TSA) on inhibition of cell
      proliferation and induction of apoptosis in human pancreatic cancer cells.
      METHODS: MTT-based cytotoxicity assay was used to evaluate the cell viability
      after treatment with TSA. Cell cycle distribution and apoptosis were examined by
      means of flow cytometry. Expression of microRNA was determined with microRNA
      array. Expression of miR-200c and miR-21 was detected by Northern blotting.
      RESULTS: TSA significantly inhibited the proliferation of BxPC-3 human pancreatic
      cancer cells in a time- and dose-dependent manner. BxPC-3 cells treated with TSA
      were arrested in G0/G1 phase and were characterized by increased apoptotic rate,
      accompanied by differential expression of microRNAs. CONCLUSIONS: The results
      suggest that TSA may activate expression of microRNAs that may act as tumor
      suppressor in human pancreatic cancer cell line BxPC-3.

PMID- 19112424
TI  - Effect of interleukins response to ECM-induced acquisition of drug resistance in
      MCF-7 cells.
AB  - AIM: To examine the effect of various components of extracellular matrix (ECM) on
      acquisition of drug resistance to taxol and camptothecin by breast carcinoma cell
      line MCF-7. METHODS: Cancer cells were cultured on bovine serum albumin (BSA),
      vitronectin (VN), fibronectin (FN), collagen type I (COL-I), or Matrigel-coated
      plates with or without taxol (paclitaxel) or camptothecin treatment. The effect
      of anticancer drugs on cell growth was accessed by XTT assay, and the alterations
      of cellular morphology were examined by phase contrast microscopy.
      Immunofluorescence study was performed using monoclonal anti-beta-tubulin
      antibody. RESULTS: All cell lines showed a significant decrease in cell survival
      when treated with anticancer drugs without components of ECM, whereas survival
      rates of Caco-2, MCF-7 and NCI-H292 were significantly increased when cells were
      cultured on COL-I- and Matrigel-coated dishes after treatment with paclitaxel or
      camptothecin. MCF-7 cells showed and maintained a colony formation when cultured
      on the COL-I- and Matrigel-coated dish. Moreover, cytotoxicity (IC50) was
      decreased by taxol (paclitaxel) or camptothecin treatment during colony formation
      in MCF-7 cells, suggesting that morphological changes could increase survival of
      cells treated with anticancer drugs. Thick circumferential bundles of
      microtubules around the periphery of the cells and chromatin condensation was not
      observed for MCF-7 cells on COL-I- and Matrigel-coated dishes treated with
      paclitaxel. To confirm this, spheroid cells were prepared, and we found that
      cytotoxicity was decreased for these cells, and significantly increased when
      cells were co-cultured on Matrigel- or COL-I-coated upper wells. The effect of
      anticancer drugs on cell survival was efficiently inhibited by interleukin-6 (IL
      6) and interleukin-8 (IL-8). CONCLUSIONS: Present results suggested that not only
      integrin-ECM interactions but also other factors such as IL-6and IL-8secreted by
      cancer cells, cultured on COL-I and Matrigel dishes, are involved in the
      acquisition of drug resistance by MCF-7.

PMID- 19112425
TI  - Modifying influence of prolonged action of interferon on phenotypic
      characteristics of human lung cancer cells in vitro.
AB  - AIM: To study modifying influence of interferon (IFN) on some phenotypic
      properties of human non-small-cell lung cancer cells (NSCLC) upon prolonged
      exposition of the cells with IFN. MATERIALS AND METHODS: A-549 cells were
      cultivated with IFN at increasing concentrations for a long period of time (up to
      1 year). Cell morphology and ultrastructure were studied by light and electron
      microscopy. Expression of adhesion protein E-cadherin, and vimentin, cytosceleton
      protein associated with tumor cell migration and invasion, antigen of
      proliferating cells Ki-67, angiogenesis-stimulating protein VEGF were studied
      using the method of immunocytochemistry. Autonomity of the cell growth was
      studied with the use of colony formation in soft agar, platting efficiency assay,
      and growth in serum-free medium. RESULTS: It has been shown that prolonged action
      of IFN results in significant and irreversible inhibition of manifestation of
      malignant phenotype: decreased of proliferative potential and inhibited autonomy
      of the cells; in complicated cell ultrastructure; in decreased expression
      vimentin and in increased expression of E-cadherin. Also, an inhibiting influence
      of IFN on expression of EGF receptors and VEGF in tumor cells have been shown.
      CONCLUSIONS: The data are showing that prolonged exposition of NSCLC cells to IFN
      is accompanied by stable phenotypic alterations of the cells directed on
      significant loss of malignancy and their shift to more differentiated phenotype.

PMID- 19112426
TI  - Aspisol inhibits tumor growth and induces apoptosis in breast cancer.
AB  - Nonsteroidal anti-inflammatory drugs inhibit cell proliferation and induce
      apoptosis in various cancer cell lines, which is considered to be an important
      mechanism for their anti-tumor activity and cancer prevention. However, the
      molecular mechanisms through which these compounds induce apoptosis are not well
      understood. AIM: to determine the effects of nonselective cyclooxygenase-2 (COX
      2) inhibitor, aspisol on breast cancer cells in vitro and in vivo. METHODS: The
      cytotoxic activity of aspisol was evaluated by MTT assay. The apoptosis index of
      cells was measured by flow cytometry. Immunohistochemical staining was used to
      detect expressions of COX-2 and caspase-3 in MDA-MB-231 cells. The expression of
      bcl-2 and bax was analyzed by Western blot analysis. The content of prostaglandin
      E2 (PGE2) in MDA-MB-231 cells was estimated by ELISA. In vivo apoptosis of the
      tumor cells was detected by the terminal deoxynucleotidyl transferase-mediated
      dUTP nick-end labeling (TUNEL). RESULTS: Our results showed that aspisol reduced
      viability of MDA-MB-231 cells in time- and dose- dependent fashions and induced
      apoptosis by increase of caspase-3 and bax expressions while decrease of COX-2
      and bcl-2 expression in vitro. In addition, exposure to aspisol decreased the
      basal release of PGE2. In vivo, aspisol also inhibited the proliferation of
      breast cancer cells and induced their apoptosis. CONCLUSIONS: Our in vitro and in
      vivo data indicated that the antitumor effects of aspisol on breast cancer cells
      was probably mediated by the induction of apoptosis, and it could be linked to
      the downregulation of the COX-2 or bcl-2 expression and up-regulation of caspase
      3 or bax expression.

PMID- 19112427
TI  - Expression of CD40 by the cells of benign and malignant breast tumors and
      antitumor action of autologous lymphocytes against chemoresistant and
      chemosensitive tumors.
AB  - AIM: To study the expression of CD40 by cells of benign and malignant tumors of
      mammary gland, and to compare the efficacy of lymphocytes antitumor activity
      against drug resistant and sensitive breast tumors in relevance to CD40
      expression. METHODS: Breast tumor explants were cultured with autologous
      lymphocytes in double diffusion chambers. The results were evaluated by
      morphological criteria of explants growth. Expression level of molecules on tumor
      cells was analyzed using immunohistochemical method (paraffin embedded slides),
      and on lymphocytes - by the method of indirect immunofluorescence. RESULTS: The
      highest level of CD40 expression was detected on cells of chemoresistant
      malignant breast tumors, and the lowest one - on cells of benign breast tumors.
      The decreased CD40 expression on lymphocytes from patients with drug resistant
      breast cancer was compared with that on lymphocytes of the patients with drug
      sensitive breast cancer. The study of antitumor activity of autologous lymphokine
      activated killer cells (LAK) has shown their pronounced antitumor activity
      against drug resistant malignant breast tumors. CONCLUSION: Marked antitumor
      activity of LAK from the patients with drug resistant breast cancer is associated
      with high expression level of CD40 on tumor cells and with its decreased
      expression on lymphocytes.

PMID- 19112428
TI  - Anti-tumor activity of murine peritoneal macrophages induced by porcine skin
      gelatin.
AB  - AIM: To study the induction of anti-tumor activity of murine peritoneal
      macrophages in vitro by porcine skin gelatin. METHODS: Anti-tumor activity of the
      macrophages was evaluated with tritium thymidine uptake by target tumor cells.
      ELISA was used to measure amounts of cytokines secreted in culture medium.
      RESULTS: The ability of the gelatin to induce anti-tumor activity of the
      macrophages was stronger than that of lipopolysaccharide of E. coli. Combination
      of the lipopolysaccharide and interferon-gamma synergistically stimulated the
      macrophages but that of the gelatin and interferon-gamma additionally did. The
      culture supernatant of the macrophages incubated with the gelatin also showed
      higher anti-tumor activity than that with the lipopolysaccharide though the
      lipopolysaccharide was more excellent than the gelatin in stimulating secretion
      of anti-tumor cytokines (IL-1, IL-6, TNF-alpha, IFN-gamma) by the macrophages.
      Anti-TNF-alpha antibody partially suppressed the anti-tumor activity of the
      culture supernatant of the macrophages incubated with the lipopolysaccharide but
      not with the gelatin. The gelatin induced anti-tumor activity of the macrophages
      of C3H/HeJ as well as C3H/HeN mice whereas the lipopolysaccharide did only in
      C3H/HeN mice. The macrophages stimulated in vitro by the gelatin exerted anti
      tumor activity in vivo. Moreover, the gelatin stimulated peritoneal exudates
      cells in vivo when subcutaneously administered with them. CONCLUSIONS: Porcine
      skin gelatin induces anti-tumor activity of macrophages in mice and its magnitude
      is greater than that of lipopolysaccharide of E. coli. Its mechanism is different
      from that of the lipopolysaccharide but not fully clarified.

PMID- 19112429
TI  - Effects of green and black tea biocomposites on endogenous synthesis, metabolism
      and genotoxic effect of carcinogenic N-nitrosodimethylamine.
AB  - AIM: To study the modifying effect of green and black tea biocomposites on
      endogenous synthesis and genotoxic action of the carcinogenic N
      nitrosodimethylamine. METHODS: Green and black tea biocomposites were
      administered to the white inbred rats in vivo. Amidopyrine and sodium nitrite
      were used as N-nitrosodimethylamine precursors and 4-methylpyrazol as an
      inhibitor of its metabolism. N-nitrosodimethylamine (blood, daily urine and
      reaction mixture), nitrites and nitrates (daily urine) levels were measured.
      Genotoxic action was tested by formation of DNA single-strand breaks in
      hepatocytes. RESULTS: In in vitro system, biocomposites increased N
      nitrosodimethylamine synthesis in neutral medium and decreased in acid
      conditions. In vivo, black tea biocomposite consumption resulted in enhanced
      background level of DNA single-strand breaks in rats hepatocytes and higher
      genotoxic effect upon administration of N-nitrosodimethylamine precursors. The
      levels of N-nitrosodimethylamine in blood and urine of experimental animals were
      increased after precursors' administration. In contrast, green tea biocomposite
      significantly decreased background level of DNA single-strand breaks. However,
      there was no protective action of this food supplement at the N
      nitrosodimethylamine, precursors' administration. 4-methylpyrazol administration
      did not increase N-nitrosodimethylamine excretion in urine, while this effect was
      observed in control and black tea biocomposite groups. CONCLUSIONS: The effects
      of green tea and black tea biocomposites on N-nitrosodimethylamine synthesis in
      in vitro system are unidirectional and depend on biocomposites' concentration and
      acidity of the medium. Long-term consumption of black tea biocomposite resulted
      in intensification of endogenous N-nitrosodimethylamine synthesis and increased
      damage of the hepatocytes' DNA. As to the green tea biocomposite, the obtained
      results allow us to suggest that this biocomposite enhanced N
      nitrosodimethylamine metabolism.

PMID- 19112430
TI  - Study of photodynamic efficiency of the hematoporphyrin conjugated with antibody
      to VEGF in mouse Lewis carcinoma.
AB  - AIM: To examine photodynamic antitumor and anti-metastatic effect of
      hematoporphyrin, conjugated with antibodies to VEGF in comparison with native
      hematoporphyrin in experiments with high metastatic, angiogenesis-independent
      Lewis carcinoma (LLC) and its low metastatic angiogenesis-dependent variant -
      LLC/R9. METHODS: Mice with LLC or with LLC/R9 were treated by photodynamic
      therapy (PDT) using new photosensitizer - hematoporphyrin conjugated with
      antibodies to VEGF, in comparison with hematoporphyrin or aminolevulinic acid.
      Tumor growth indices and metastasis incidence were calculated. RESULTS: Strong
      antitumor effect of PDT with new conjugate was demonstrated - delay of tumor
      development by 70% whereas native hematoporphyrin with the same treatment regime
      did not show any significant effect. Most pronounced effect of conjugate was
      demonstrated on the growth and metastasing of LLC/R9, which was characterized by
      the resistance to chemotherapeutic drugs. Slowdown of the tumor growth - up to
      complete regression - was detected already at the third day after PDT and, on the
      average was about 70% of control values. Non-conjugated hematoporphyrin under
      parameters chosen did not cause antitumor effect. Metastases calculation
      demonstrated that total metastatic volume reduced by seven times in conjugate
      group and by 3.5 times in hematoporphyrin group. CONCLUSION: Hematoporhyrin
      conjugate studied had high photodynamic antitumor activity. Taking into
      consideration substantial prevalence in clinical practice of drug-resistant
      tumors and angiogenesis-dependent character of metastasis process, further study
      and application of photosensitizers, conjugated with antibodies to VEGF, may help
      to improve the clinical outcomes.

PMID- 19112431
TI  - Elevation of efficacy of cancer vaccine combined with interferon and inducer of
      endogeneous interferon synthesis amixin.
AB  - AIM: To study in vivo efficacy of combined administration of cancer vaccine (CV),
      interferon (IFN) and inducer of endogenous IFN - amixin. MATERIALS AND METHODS:
      Sarcoma-37 cells were transplanted to female Balb/c mice. For the treatment, CV
      prepared from sarcoma-37 cells with the use of cytotoxic lectines from B.
      subtilis B-7025, murine IFN and amixin or their combinations were used. IFN
      production, content of circulating immune complexes and level of specific IgG
      antibodies in blood serum were determined by standard immunologic methods.
      RESULTS: Using solid form of sarcoma-37 it has been shown that introduction of
      IFN and amixin significantly elevated efficacy of vaccine therapy, in particular
      index of tumor growth inhibition reach 89.2% and 81.7%. Upon combined use of CV
      and IFN or CV and amixin (25 mg/kg) respectively. Significant prolongation of
      average life span of the animals treated with CV and IFN or CV and amixin (25
      mg/kg) has been registered (up to 92.7 -/+ 10.4 and 95.0 -/+ 6.2 days
      respectively, vs 46.8 -/+ 1.5 days for control animals). CONCLUSION: Obtained
      results have shown expediency of the development of schemes for combined
      introduction of CV with exogenous IFN, and with inducer of endogenous IFN
      (amixin) for elevation of efficacy of vaccine therapy.

PMID- 19112432
TI  - Breast cancer with diabetes insipidus.
AB  - Diabetes insipidus (DI) is a rare clinical condition, which is usually caused by
      neurohypophyseal or pituitary stalk infiltration in cancer patients. CASE REPORT:
      we present a 62-year old metastatic breast cancer woman with DI. She admitted to
      the hospital because of nausea, vomiting, polyuria and polydipsia, while she was
      on no cytotoxic medication. She had no electrolyte imbalance except mild
      hypernatremia. The CT scan of the brain yielded a suspicious area in pituitary
      gland. A pituitary stalk metastasis was found on magnetic resonance imaging (MRI)
      of pituitary. Water deprivation test was compatible with DI. A clinical response
      to nasal vasopressin was achieved. CONCLUSIONS: Cancer patients who have symptoms
      such as nausea, vomiting, polyuria and polydipsia while they are not on
      chemotherapy should be evaluated for not only metabolic complications like
      hypercalcemia but also posterior pituitary or stalk metastasis MRI could be the
      choice of imaging for pituitary metastasis.

PMID- 19112439
TI  - Response to protocol review scenario: the bow and the lyre.

PMID- 19112433
TI  - Immunofluorescence staining of paraffin sections: creating DAB staining like
      virtual digital images using CMYK color conversion.
AB  - Crystal violet treatment of formalin fixed paraffin embedded tissue slides
      greatly reduces the endogenous autofluorescence, and allows immunofluorescence
      (IF) staining with FITC or Alexa488 conjugated antibodies. Using cold CCD camera
      to capture the fluorescence images makes this staining method very sensitive.
      Here we show that combination of IF with the simultaneous recording of crystal
      violet induced red and Hoechst 33258 induced blue fluorescence permits the
      localization of the IF signal over a cytoplasmic: nuclear red:blue stain that
      visualizes the microscopic anatomy of the underlying tissue. To make the visual
      interpretation of the IF staining easier for microscopists, who are used to DAB
      staining over weak hematoxilin-eosin background, we created a simple color
      conversion procedure that turns the captured three-color fluorescence RGB (red,
      green, blue) images over a black background into four color CMYK (cyan, magenta,
      yellow, key color (black)) images.

PMID- 19112440
TI  - Clinical care or protocol violation?

PMID- 19112441
TI  - Response to protocol review scenario: report unexpected pain.

PMID- 19112442
TI  - Response to protocol review scenario: clinical scoring system and pilot study.

PMID- 19112443
TI  - Pelvic limb lameness in a ferret.

PMID- 19112444
TI  - Diagnosis: rupture of the caudal cruciate ligament.

PMID- 19112445
TI  - Management of freshwater turtle shell injuries.
AB  - Repair of injured turtle shells can be difficult and time-consuming. This article
      describes how to manage the freshwater turtle in this phase of healing and how to
      keep fracture sites 'water-free'.

PMID- 19112446
TI  - Ammonia and carbon dioxide concentrations in disposable and reusable static mouse
      cages.
AB  - The value of a static mouse cage is partially determined by the cage's ability to
      dissipate carbon dioxide and ammonia. The authors compared the concentrations of
      ammonia and carbon dioxide produced by mice housed in two types of static
      isolator cages: a newly introduced disposable cage and a conventional reusable
      cage. Female mice were housed in three disposable and three reusable cages (n = 5
      per cage). After 7 d, groups that were housed in disposable cages were rehoused
      in fresh reusable cages and vice versa. Intracage carbon dioxide, ammonia,
      temperature and relative humidity were measured daily. Overall, there were no
      significant differences in carbon dioxide or ammonia concentrations between the
      cage types. Within 30 min of placing mice in cages, carbon dioxide concentrations
      rose to more than 10,000 ppm in both cage types and rarely dropped below 8,000
      ppm during both phases of the study. Ammonia concentrations rose slowly until day
      4 and then began to rise rapidly. The maximum average ammonia concentration was
      710 ppm. There was a highly significant relationship between increasing levels of
      humidity and ammonia production in the disposable cages (r = 0.88). For the
      reusable cages, the correlation was not as strong (r = 0.68). Both cage types
      were similar in their ability to dissipate carbon dioxide and ammonia. The
      suggested frequency of cage changing can only be estimated; on the basis of
      existing literature, it seems prudent to change cages when the ammonia
      concentration reaches 50 ppm.

PMID- 19112447
TI  - Effects of cage size and enrichment on reproductive performance and behavior in
      C57BL/6Tac mice.
AB  - The authors examined the effects of cage size and enrichment on mouse breeding
      performance and behavior. Breeding trios of C57BL/6Tac mice were housed in cages
      of two different sizes ('standard' and 'large' cages with 82 in(2) and 124 in(2)
      floor space, respectively). Half of the cages of each size contained four
      enrichment items (Nestlet, plastic tunnel, nylon rings and running wheel),
      whereas the remaining cages had no enrichment. The authors measured the following
      reproductive parameters: litter size, number of pups that survived to weaning
      age, average pup weights at 21 d after birth and number of days between births of
      litters. A subset of weaned male and female pups from each cage size and
      enrichment condition completed a suite of behavioral tests. Pups raised in large
      cages weighed less than those raised in standard cages. Enrichment and cage size
      had certain behavioral effects, which were dependent on gender and behavioral
      measure. Male pups born in enriched cages showed more anxiety-like behavior and
      less exploration than did males born in non-enriched cages. Though being raised
      in enriched or large cages did not clearly improve pups' performance in
      behavioral tests, enrichment (regardless of cage size) did significantly benefit
      reproductive performance; pups from non-enriched cages weighed less than pups
      from enriched cages, and fewer survived to weaning age.

PMID- 19112448
TI  - A method for gender determination in newborn dark pigmented mice.
AB  - In many studies using mice, investigators must determine pups' gender at a very
      early postnatal stage. The gender of mouse pups is typically assessed by
      measuring the anogenital distance, which is greater in males than in females.
      This method, however, has proven to be difficult and not completely reliable. The
      authors describe a quick, easy and reliable method to establish the gender of
      pigmented mice. In male mice, a pigment spot on the scrotum is visible to the
      naked eye from the first day of life onwards, whereas female pups lack visible
      pigmentation in the anogenital region. In lightly pigmented or albino mice, the
      pigmentation is not obvious or not at all visible. The authors show that
      identifying this pigment spot is a more accurate and efficient method of
      determining pup gender compared with measurement of the anogenital distance. This
      'spot on' method would therefore be a useful adjunct to conventional methods for
      determining the gender of pigmented neonatal mice.

PMID- 19112451
TI  - Who's on first?

PMID- 19112449
TI  - Lentivectors encoding immunosuppressive proteins genetically engineer pancreatic
      beta-cells to correct diabetes in allogeneic mice.
AB  - The effectiveness of genetic engineering with lentivectors to protect
      transplanted cells from allogeneic rejection was examined using, as a model, type
      1 diabetes treatment with beta-cell transplantation, whose widespread use has
      been limited by the requirement for sustained immunosuppressive treatment to
      prevent graft rejection. We examined whether lentivectors expressing select
      immunosuppressive proteins encoded by the adenoviral genome early region 3 (AdE3)
      would protect transplanted beta-cells from an alloimmune attack. The insulin
      producing beta-cell line beta TC-tet (C3HeB/FeJ-derived) was transduced with
      lentiviruses encoding the AdE3 proteins gp19K and RID alpha/beta. The efficiency
      of lentiviral transduction of beta TC-tet cells exceeded 85%. Lentivector
      expression of gp19K decreased surface class I major histocompatibility complex
      expression by over 90%, whereas RID alpha/beta expression inhibited cytokine
      induced Fas upregulation by over 75%. beta TC-tet cells transduced with gp19K and
      RID alpha/beta lentivectors, but not with a control lentivector, provided
      prolonged correction of hyperglycemia after transplantation into diabetic BALB/c
      severe combined immunodeficient mice reconstituted with allogeneic immune
      effector cells or into diabetic allogeneic BALB/c mice. Thus, genetic engineering
      of beta-cells using gp19K- and RID alpha/beta-expressing lentiviral vectors may
      provide an alternative that has the potential to eliminate or reduce treatment
      with the potent immunosuppressive agents necessary at present for prolonged
      engraftment with transplanted islets.

PMID- 19112453
TI  - Teamwork.

PMID- 19112455
TI  - Cohort studies and the genetics of complex disease.

PMID- 19112456
TI  - Searching for targets of viral microRNAs.

PMID- 19112457
TI  - Evaluating signatures of sex-specific processes in the human genome.

PMID- 19112458
TI  - Protein demethylation required for DNA methylation.

PMID- 19112460
TI  - Metastatic non-small-cell lung cancer and the use of gemcitabine during
      pregnancy.
AB  - We present a case of metastatic non-small-cell lung malignancy diagnosed in the
      mother in her 24th week of pregnancy and illustrate the obstetric, oncology,
      neonatal and ethical issues involved. This is the second reported case on the use
      of gemcitabine for lung cancer in human pregnancy.

PMID- 19112461
TI  - Persistent vancomycin and high-level gentamicin-resistant Enterococcus faecium
      bacteremia and intra-aortic thrombus in an extremely low birth-weight infant.
AB  - Vancomycin-resistant Enterococcus (VRE) sepsis is emerging as a significant
      problem in the intensive care setting. The treatment at any age is challenging,
      but there is a dearth of information on this infection and its treatment in the
      very premature infant. We describe successful treatment of persistent bacteremia
      caused by Enterococcus faecium with vancomycin and high-level gentamicin
      resistance in a 10-day-old former 23-week premature male infant.

PMID- 19112462
TI  - Prune belly syndrome.

PMID- 19112463
TI  - Corrections regarding lucinactant and clinical trials involving lucinactant.

PMID- 19112465
TI  - Reducing neonatal mortality in developing countries: low-cost interventions are
      the key determinants.

PMID- 19112467
TI  - Sphingosylphosphorylcholine induces mitochondria-mediated apoptosis in neuro 2a
      cells: involvement of protein kinase C.
AB  - We demonstrate that sphingosylphosphorylcholine-mediated cell death involves the
      activation of different protein kinase C isozymes in different manners. Treating
      cells with sphingosylphosphorylcholine resulted in activation of protein kinase C
      delta, which is necessary, together with elevation of Ca2+ for
      sphingosylphosphorylcholine-induced apoptosis. A rapid translocation from cytosol
      to membrane, and a proteolytic protein kinase C delta cleavage was found,
      probably due to activation of caspase-3, to give a catalytically active fragment
      involved in cellular apoptosis. Moreover, sphingosylphosphorylcholine also
      induced translocation of protein kinase C zeta, resulting in an anti-apoptotic
      effect. To explore whether a mitochondrial pathway is involved in
      sphingosylphosphorylcholine-induced apoptosis, we analyzed the effect of
      sphingosylphosphorylcholine on cytochrome c release and caspase-3 activity. We
      must point out that the sphingolipid caused an increase of cytochrome c release
      from mitochondria to cytosol concomitantly with an increase of caspase-3
      activity. Furthermore, a translocation of Bax was found, after
      sphingosylphosphorylcholine treatment.

PMID- 19112468
TI  - Effects of lead on cholinergic SN56 neuroblastoma cells.
AB  - Age-dependent accumulation of lead in brain has been implicated in the
      pathomechanisms of Alzheimer's disease. The aim of this work was to investigate
      whether cholinotoxic effects of lead may result from alterations in acetyl-CoA
      metabolism. One day exposure of differentiated SN56 cholinergic neuroblastoma
      cells to 0.5 micromol/L lead or 0.01 mmol/L amyloid-beta1-42, increased fraction
      of nonviable cells to about 2%. Suppression of choline acetyltransferase activity
      occurred only in the presence of fresh amyloid-beta1-42, whereas lead was
      ineffective. All agents in combination caused suppression of acetyl-CoA in
      cytoplasm and mitochondria down to 19% and 34% of controls, respectively. Inverse
      correlation was observed between whole cell acetyl-CoA level and fraction of
      nonviable cells at different combinations of lead and other neurotoxic compounds.
      It indicates that lead had no primary suppressive effect on cholinergic phenotype
      but, at least in part, exerted cytotoxic influence on cholinergic neurons through
      the decrease of their acetyl-CoA.

PMID- 19112469
TI  - Different sensitivity of neurons and neuroblastoma cells to quercetin treatment.
AB  - Quercetin is a natural flavonoid with pro-apoptotic and antiproliferative
      properties. In this study, we determined the sensitivity of neurons and
      neuroblastoma cells on apoptosis and necrosis induction upon quercetin treatment.
      No expression of Hsp72 was observed in neurons, which were more sensitive to cell
      death upon quercetin treatment than neuroblastoma cells, where Hsp72 expression
      was observed. Reduction of Hsp72 gene expression in neuroblastoma cells by
      antisense oligonucleotides made them more sensitive to pro-apoptotic action of
      quercetin. Moreover, the flavonoid decreased Hsp27, procaspase-3, MRP and PKB
      expression in neuroblastoma cells and in neurons. Nuclear localization of mainly
      cytoplasmic Hsp27 was observed in neuroblastoma cells after treatment with high
      quercetin concentrations, while in neurons, the protein was present in nuclei
      both in control and quercetin treated cells. Our results suggest that quercetin
      induce apoptosis more effectively in cells with low level of Hsp 72 expression.
      Higher sensitivity of neurons for cell death after treatment with high quercetin
      concentrations in comparison to neuroblastoma cell line should also be taken into
      consideration in further studies on using studied flavonoid as therapeutic agent.

PMID- 19112470
TI  - Effect of FK506 administration after obturator nerve injury: a functional and
      ultrastructural study.
AB  - The frequency of obturator nerve damage due to pelvic diseases, fractures or
      gynecologic procedures is uncertain. In the present study, we investigated the
      effect of FK506, a potent macrolide antibiotic and immunosuppresant, on obturator
      nerve recovery at morphological and functional levels. Forty female Wistar rats
      were randomly divided into four groups (control, sham, FK506-treated, vehicle
      treated). In half of animals (FK506-treated and vehicle-treated) an obturator
      nerve crush (30 seconds clamp) was created. In FK506-treated group FK506
      administration (1 mg/kg/day, subcutaneously) was performed on each postoperative
      day. All the rats were functionally evaluated by pinch and adduction tests
      preoperatively and postoperatively at one, two, three and four weeks after nerve
      injury. On the 28th postoperative day obturator nerve samples were collected and
      analyzed qualitatively by light and electron microscopy. FK506 treatment resulted
      in dramatic improvement in nerve function and in the ultrastructure of nerve
      fibers suggesting its therapeutic potential in traumatic obturator nerve injury.

PMID- 19112471
TI  - Early postnatal ethanol exposure induces fluctuation in the expression of BDNF
      mRNA in the developing rat hippocampus.
AB  - Effects of early postnatal ethanol exposure on brain-derived neurotrophic factor
      (BDNF) mRNA expression in the rat hippocampus were investigated. Wistar rats were
      assigned to either ethanol treatment (ET) separation control (SC) or mother
      reared control (MRC) groups. Ethanol exposure was achieved by a vapor inhalation
      method for 3 hours a day between postnatal days (PND) 1015. On PND 16, 20, 30,
      and 60, the expression of BDNF mRNA in the hippocampus was determined using real
      time RT-PCR analysis. There was a significant age-related increase in the BDNF
      mRNA expression between PND 3060 in MRC animals. The BDNF mRNA expression in ET
      rats was increased at both PND 16 and 20 and thereafter decreased at PND 60
      compared to SC animals. Such age-related fluctuation in the expression of BDNF
      mRNA differed from that of MRC animals. The exact functional implications, if
      any, of these ethanol-induced changes in BDNF mRNA expression remain unknown
      although it can be speculated that they may have an effect on the behaviors known
      to be influenced by the hippocampal formation.

PMID- 19112472
TI  - Effects of intra-hippocampal D-AP5 injections on one trial passive avoidance
      learning in adult laying hens (Gallus gallus domesticus).
AB  - Domestic chickens are an established model organism for studies on learning and
      memory. Commonly, the chicks are used as subjects in several different learning
      tests, including one trial learning tests. However, for adult laying hens no such
      one trial learning tests have been established. In particular, there is no test
      established which focuses on the role of the hippocampus, a brain region, which
      is often critically involved in learning and memory consolidation. In this study
      we investigated the inhibitory effects of intra-hippocampal D-AP5 injections on a
      specific one trial passive avoidance learning test in adult laying hens (Gallus
      gallus domesticus). We used a step down avoidance learning paradigm (SDA) which
      is frequently used in rodents. Intra-hippocampal injections of D-AP5 impaired the
      learning abilities of adult laying hens compared to sham-injected control
      subjects. Thus, the experiments revealed that the hippocampus is critically
      involved in learning the inhibitory SDA task. Our results further indicate that
      the step down avoidance paradigm is suitable to examine learning and memory
      processes in adult laying hens.

PMID- 19112473
TI  - Maternal behavior in a genetic animal model of absence epilepsy.
AB  - In this study we quantified maternal behavior in genetic epileptic rats with
      deficiencies in the DA system known to be involved in maternal behavior in order
      to assess whether these rats have disturbances in maternal care. Wistar Albino
      Glaxo/Rijswijk (WAG/Rij) rats, a genetic model for generalized absence epilepsy
      and Wistar rats were compared. Maternal behavior parameters and activity scores
      were quantified from post-natal day (PND) 4-6 in an open field in the presence of
      pups. WAG/Rij rats had less approaches to the pups and higher latencies of
      approaching them compared to Wistar, while locomotion showed a different pattern
      over days. This confirms the hypothesis that animals with absence epilepsy show
      more poor maternal behavior and that these effects cannot be solely attributed to
      differences in locomotor activity. It is proposed that the reduction in maternal
      care is attributed to low activity in the mesolimbic DA system.

PMID- 19112474
TI  - Alpha-synuclein is localized in a subpopulation of rat brain synaptic vesicles.
AB  - Alpha-synuclein is a neuronal protein implicated both in synaptic transmission
      and in neurodegenerative diseases. Although it is evident that this protein is
      enriched in the presynaptic terminals of neurons, localization in synaptic
      vesicles has not been conclusively determined. Here, we show that alpha-synuclein
      is present, but not enriched, in synaptic vesicles using highly purified synaptic
      vesicle preparations from rat brain homogenate. Immunoisolation of vesicles using
      antibodies against synaptophysin or synaptobrevin confirmed the presence of alpha
      synuclein in synaptic vesicles. Additional separation of synaptic vesicles by
      sucrose velocity centrifugation showed that there are different subpopulations of
      synaptic vesicles and that alpha-synuclein is present only in a specific
      subpopulation, whereas synaptophysin and synaptobrevin were found in all the
      synaptic vesicles. Presence of alpha-synuclein only in a subset of synaptic
      vesicles suggests that this protein may have a specific function in synaptic
      vesicle cycling, hence in synaptic transmission.

PMID- 19112475
TI  - The modified Color Density Spectral Array--an alternative method for sleep
      presentation.
AB  - The modified Color Density Spectral Array (CDSA) method used for graphical
      representation of sleep patterns is described in this article. CDSA was presented
      for the first time in 1987 by M. Salinsky and coauthors. This method was adapted
      to display frequency course and voltage of EEG signal during sleep. The overnight
      sleep records of 35 healthy volunteers of both sexes (23 women, 12 men; aged 19
      26) were analyzed in order to verify the modification of CDSA method. We propose
      to use combining the hypnogram and CDSA method significantly increases the
      informative value of data and results in enhanced quality of sleep analysis.

PMID- 19112476
TI  - Telencephalon ablation impairs goldfish allocentric spatial learning in a "hole
      board" task.
AB  - The present work analyzes the involvement of telencephalon of goldfish in spatial
      strategies, using a procedure analogue to the hole-board task. With this aim,
      goldfish with sham operation or telencephalon ablation were trained to find a
      baited feeder within a twenty-five feeder matrix, which maintained stable spatial
      relationships relative to five peripheral landmarks. After training, different
      types of probe tests were conducted. Although both groups learned the task, probe
      trials showed that whereas the sham animals used the whole configuration of cues
      to implement map-like strategies the telencephalic animals used a guidance
      strategy based on cues located in the vicinity of the baited feeder. These
      results confirm the role of teleost fish telencephalon in the use of allocentric
      strategies obtained with other spatial procedures, and indicate that the hole
      board task described here for goldfish is a useful tool to assess the neural
      bases of spatial cognition in teleost fish.

PMID- 19112477
TI  - Pro-inflammatory cytokine TNF-alpha as a neuroprotective agent in the brain.
AB  - Despite the numerous reports on the role of tumor necrosis factor-alpha (TNF
      alpha) in the brain neuropathology, very little is known about the mechanisms by
      which TNF-alpha may mediate neuroprotection. Different hypotheses pertain to the
      molecular and cellular effectors triggered by the activation of TNF receptors
      (TNFRI and TNFR2). They are focused on diminishing the production of nitric oxide
      and free radicals, alteration of excitatory amino acids neurotransmission,
      maintenance of neuronal calcium homeostasis and induction of neurotrophic factors
      synthesis. In this review all these data are summarized. Moreover, possible
      explanations for the inconsistent data concerning the TNF-alpha effect on neuron
      are discussed.

PMID- 19112478
TI  - Synthesis and characterization of aryl thioacetyl styrene monomers: Towards a new
      generation of SERS-active polymers.
AB  - A new family of thioacetyl styrene derivatives was synthesized in good isolated
      yields for the preparation of spectroscopically-encoded SERS-active polymers.

PMID- 19112479
TI  - Synthesis of Substituted 2-phenylhistamines via a Microwave Promoted Suzuki
      Coupling.
AB  - Substitutions on the 2-position of the imidizole ring of histamine have proven
      useful in a number of biochemical settings. Current art for the synthesis of
      these constructs relies upon a cumbersome and low-yielding condensation reaction.
      Here-in we report a new procedure for the synthesis of a series of substituted 2
      phenylhistamines utilizing a microwave-promoted Suzuki coupling.

PMID- 19112480
TI  - I am not a scientist, I am a number.

PMID- 19112481
TI  - The morphological identity of insect dendrites.
AB  - Dendrite morphology, a neuron's anatomical fingerprint, is a neuroscientist's
      asset in unveiling organizational principles in the brain. However, the genetic
      program encoding the morphological identity of a single dendrite remains a
      mystery. In order to obtain a formal understanding of dendritic branching, we
      studied distributions of morphological parameters in a group of four individually
      identifiable neurons of the fly visual system. We found that parameters relating
      to the branching topology were similar throughout all cells. Only parameters
      relating to the area covered by the dendrite were cell type specific. With these
      areas, artificial dendrites were grown based on optimization principles
      minimizing the amount of wiring and maximizing synaptic democracy. Although the
      same branching rule was used for all cells, this yielded dendritic structures
      virtually indistinguishable from their real counterparts. From these principles
      we derived a fully-automated model-based neuron reconstruction procedure
      validating the artificial branching rule. In conclusion, we suggest that the
      genetic program implementing neuronal branching could be constant in all cells
      whereas the one responsible for the dendrite spanning field should be cell
      specific.

PMID- 19112482
TI  - A mathematical framework for the selection of an optimal set of peptides for
      epitope-based vaccines.
AB  - Epitope-based vaccines (EVs) have a wide range of applications: from therapeutic
      to prophylactic approaches, from infectious diseases to cancer. The development
      of an EV is based on the knowledge of target-specific antigens from which
      immunogenic peptides, so-called epitopes, are derived. Such epitopes form the key
      components of the EV. Due to regulatory, economic, and practical concerns the
      number of epitopes that can be included in an EV is limited. Furthermore, as the
      major histocompatibility complex (MHC) binding these epitopes is highly
      polymorphic, every patient possesses a set of MHC class I and class II molecules
      of differing specificities. A peptide combination effective for one person can
      thus be completely ineffective for another. This renders the optimal selection of
      these epitopes an important and interesting optimization problem. In this work we
      present a mathematical framework based on integer linear programming (ILP) that
      allows the formulation of various flavors of the vaccine design problem and the
      efficient identification of optimal sets of epitopes. Out of a user-defined set
      of predicted or experimentally determined epitopes, the framework selects the set
      with the maximum likelihood of eliciting a broad and potent immune response. Our
      ILP approach allows an elegant and flexible formulation of numerous variants of
      the EV design problem. In order to demonstrate this, we show how common
      immunological requirements for a good EV (e.g., coverage of epitopes from each
      antigen, coverage of all MHC alleles in a set, or avoidance of epitopes with high
      mutation rates) can be translated into constraints or modifications of the
      objective function within the ILP framework. An implementation of the algorithm
      outperforms a simple greedy strategy as well as a previously suggested
      evolutionary algorithm and has runtimes on the order of seconds for typical
      problem sizes.

PMID- 19112483
TI  - Search algorithms as a framework for the optimization of drug combinations.
AB  - Combination therapies are often needed for effective clinical outcomes in the
      management of complex diseases, but presently they are generally based on
      empirical clinical experience. Here we suggest a novel application of search
      algorithms -- originally developed for digital communication -- modified to
      optimize combinations of therapeutic interventions. In biological experiments
      measuring the restoration of the decline with age in heart function and exercise
      capacity in Drosophila melanogaster, we found that search algorithms correctly
      identified optimal combinations of four drugs using only one-third of the tests
      performed in a fully factorial search. In experiments identifying combinations of
      three doses of up to six drugs for selective killing of human cancer cells,
      search algorithms resulted in a highly significant enrichment of selective
      combinations compared with random searches. In simulations using a network model
      of cell death, we found that the search algorithms identified the optimal
      combinations of 6-9 interventions in 80-90% of tests, compared with 15-30% for an
      equivalent random search. These findings suggest that modified search algorithms
      from information theory have the potential to enhance the discovery of novel
      therapeutic drug combinations. This report also helps to frame a biomedical
      problem that will benefit from an interdisciplinary effort and suggests a general
      strategy for its solution.

PMID- 19112484
TI  - Mechanics and dynamics of X-chromosome pairing at X inactivation.
AB  - At the onset of X-chromosome inactivation, the vital process whereby female
      mammalian cells equalize X products with respect to males, the X chromosomes are
      colocalized along their Xic (X-inactivation center) regions. The mechanism
      inducing recognition and pairing of the X's remains, though, elusive. Starting
      from recent discoveries on the molecular factors and on the DNA sequences (the so
      called "pairing sites") involved, we dissect the mechanical basis of Xic
      colocalization by using a statistical physics model. We show that soluble DNA
      specific binding molecules, such as those experimentally identified, can be
      indeed sufficient to induce the spontaneous colocalization of the homologous
      chromosomes but only when their concentration, or chemical affinity, rises above
      a threshold value as a consequence of a thermodynamic phase transition. We derive
      the likelihood of pairing and its probability distribution. Chromosome dynamics
      has two stages: an initial independent Brownian diffusion followed, after a
      characteristic time scale, by recognition and pairing. Finally, we investigate
      the effects of DNA deletion/insertions in the region of pairing sites and compare
      model predictions to available experimental data.

PMID- 19112485
TI  - Identification of mechanosensitive genes during embryonic bone formation.
AB  - Although it is known that mechanical forces are needed for normal bone
      development, the current understanding of how biophysical stimuli are interpreted
      by and integrated with genetic regulatory mechanisms is limited. Mechanical
      forces are thought to be mediated in cells by "mechanosensitive" genes, but it is
      a challenge to demonstrate that the genetic regulation of the biological system
      is dependant on particular mechanical forces in vivo. We propose a new means of
      selecting candidate mechanosensitive genes by comparing in vivo gene expression
      patterns with patterns of biophysical stimuli, computed using finite element
      analysis. In this study, finite element analyses of the avian embryonic limb were
      performed using anatomically realistic rudiment and muscle morphologies, and
      patterns of biophysical stimuli were compared with the expression patterns of
      four candidate mechanosensitive genes integral to bone development. The
      expression patterns of two genes, Collagen X (ColX) and Indian hedgehog (Ihh),
      were shown to colocalise with biophysical stimuli induced by embryonic muscle
      contractions, identifying them as potentially being involved in the
      mechanoregulation of bone formation. An altered mechanical environment was
      induced in the embryonic chick, where a neuromuscular blocking agent was
      administered in ovo to modify skeletal muscle contractions. Finite element
      analyses predicted dramatic changes in levels and patterns of biophysical
      stimuli, and a number of immobilised specimens exhibited differences in ColX and
      Ihh expression. The results obtained indicate that computationally derived
      patterns of biophysical stimuli can be used to inform a directed search for genes
      that may play a mechanoregulatory role in particular in vivo events or processes.
      Furthermore, the experimental data demonstrate that ColX and Ihh are involved in
      mechanoregulatory pathways and may be key mediators in translating information
      from the mechanical environment to the molecular regulation of bone formation in
      the embryo.

PMID- 19112486
TI  - Tag-trigger-consolidation: a model of early and late long-term-potentiation and
      depression.
AB  - Changes in synaptic efficacies need to be long-lasting in order to serve as a
      substrate for memory. Experimentally, synaptic plasticity exhibits phases
      covering the induction of long-term potentiation and depression (LTP/LTD) during
      the early phase of synaptic plasticity, the setting of synaptic tags, a trigger
      process for protein synthesis, and a slow transition leading to synaptic
      consolidation during the late phase of synaptic plasticity. We present a
      mathematical model that describes these different phases of synaptic plasticity.
      The model explains a large body of experimental data on synaptic tagging and
      capture, cross-tagging, and the late phases of LTP and LTD. Moreover, the model
      accounts for the dependence of LTP and LTD induction on voltage and presynaptic
      stimulation frequency. The stabilization of potentiated synapses during the
      transition from early to late LTP occurs by protein synthesis dynamics that are
      shared by groups of synapses. The functional consequence of this shared process
      is that previously stabilized patterns of strong or weak synapses onto the same
      postsynaptic neuron are well protected against later changes induced by LTP/LTD
      protocols at individual synapses.

PMID- 19112487
TI  - A common cortical circuit mechanism for perceptual categorical discrimination and
      veridical judgment.
AB  - Perception involves two types of decisions about the sensory world:
      identification of stimulus features as analog quantities, or discrimination of
      the same stimulus features among a set of discrete alternatives. Veridical
      judgment and categorical discrimination have traditionally been conceptualized as
      two distinct computational problems. Here, we found that these two types of
      decision making can be subserved by a shared cortical circuit mechanism. We used
      a continuous recurrent network model to simulate two monkey experiments in which
      subjects were required to make either a two-alternative forced choice or a
      veridical judgment about the direction of random-dot motion. The model network is
      endowed with a continuum of bell-shaped population activity patterns, each
      representing a possible motion direction. Slow recurrent excitation underlies
      accumulation of sensory evidence, and its interplay with strong recurrent
      inhibition leads to decision behaviors. The model reproduced the monkey's
      performance as well as single-neuron activity in the categorical discrimination
      task. Furthermore, we examined how direction identification is determined by a
      combination of sensory stimulation and microstimulation. Using a population
      vector measure, we found that direction judgments instantiate winner-take-all
      (with the population vector coinciding with either the coherent motion direction
      or the electrically elicited motion direction) when two stimuli are far apart, or
      vector averaging (with the population vector falling between the two directions)
      when two stimuli are close to each other. Interestingly, for a broad range of
      intermediate angular distances between the two stimuli, the network displays a
      mixed strategy in the sense that direction estimates are stochastically produced
      by winner-take-all on some trials and by vector averaging on the other trials, a
      model prediction that is experimentally testable. This work thus lends support to
      a common neurodynamic framework for both veridical judgment and categorical
      discrimination in perceptual decision making.

PMID- 19112488
TI  - Game theory of mind.
AB  - This paper introduces a model of 'theory of mind', namely, how we represent the
      intentions and goals of others to optimise our mutual interactions. We draw on
      ideas from optimum control and game theory to provide a 'game theory of mind'.
      First, we consider the representations of goals in terms of value functions that
      are prescribed by utility or rewards. Critically, the joint value functions and
      ensuing behaviour are optimised recursively, under the assumption that I
      represent your value function, your representation of mine, your representation
      of my representation of yours, and so on ad infinitum. However, if we assume that
      the degree of recursion is bounded, then players need to estimate the opponent's
      degree of recursion (i.e., sophistication) to respond optimally. This induces a
      problem of inferring the opponent's sophistication, given behavioural exchanges.
      We show it is possible to deduce whether players make inferences about each other
      and quantify their sophistication on the basis of choices in sequential games.
      This rests on comparing generative models of choices with, and without,
      inference. Model comparison is demonstrated using simulated and real data from a
      'stag-hunt'. Finally, we note that exactly the same sophisticated behaviour can
      be achieved by optimising the utility function itself (through prosocial
      utility), producing unsophisticated but apparently altruistic agents. This may be
      relevant ethologically in hierarchal game theory and coevolution.

PMID- 19112489
TI  - Gata3 acts downstream of beta-catenin signaling to prevent ectopic metanephric
      kidney induction.
AB  - Metanephric kidney induction critically depends on mesenchymal-epithelial
      interactions in the caudal region of the nephric (or Wolffian) duct. Central to
      this process, GDNF secreted from the metanephric mesenchyme induces ureter
      budding by activating the Ret receptor expressed in the nephric duct epithelium.
      A failure to regulate this pathway is believed to be responsible for a large
      proportion of the developmental anomalies affecting the urogenital system. Here,
      we show that the nephric duct-specific inactivation of the transcription factor
      gene Gata3 leads to massive ectopic ureter budding. This results in a spectrum of
      urogenital malformations including kidney adysplasia, duplex systems, and
      hydroureter, as well as vas deferens hyperplasia and uterine agenesis. The
      variability of developmental defects is reminiscent of the congenital anomalies
      of the kidney and urinary tract (CAKUT) observed in human. We show that Gata3
      inactivation causes premature nephric duct cell differentiation and loss of Ret
      receptor gene expression. These changes ultimately affect nephric duct epithelium
      homeostasis, leading to ectopic budding of interspersed cells still expressing
      the Ret receptor. Importantly, the formation of these ectopic buds requires both
      GDNF/Ret and Fgf signaling activities. We further identify Gata3 as a central
      mediator of beta-catenin function in the nephric duct and demonstrate that the
      beta-catenin/Gata3 pathway prevents premature cell differentiation independently
      of its role in regulating Ret expression. Together, these results establish a
      genetic cascade in which Gata3 acts downstream of beta-catenin, but upstream of
      Ret, to prevent ectopic ureter budding and premature cell differentiation in the
      nephric duct.

PMID- 19112490
TI  - Surviving mousepox infection requires the complement system.
AB  - Poxviruses subvert the host immune response by producing immunomodulatory
      proteins, including a complement regulatory protein. Ectromelia virus provides a
      mouse model for smallpox where the virus and the host's immune response have co
      evolved. Using this model, our study investigated the role of the complement
      system during a poxvirus infection. By multiple inoculation routes, ectromelia
      virus caused increased mortality by 7 to 10 days post-infection in C57BL/6 mice
      that lack C3, the central component of the complement cascade. In C3(-/-) mice,
      ectromelia virus disseminated earlier to target organs and generated higher peak
      titers compared to the congenic controls. Also, increased hepatic inflammation
      and necrosis correlated with these higher tissue titers and likely contributed to
      the morbidity in the C3(-/-) mice. In vitro, the complement system in naive
      C57BL/6 mouse sera neutralized ectromelia virus, primarily through the
      recognition of the virion by natural antibody and activation of the classical and
      alternative pathways. Sera deficient in classical or alternative pathway
      components or antibody had reduced ability to neutralize viral particles, which
      likely contributed to increased viral dissemination and disease severity in vivo.
      The increased mortality of C4(-/-) or Factor B(-/-) mice also indicates that
      these two pathways of complement activation are required for survival. In
      summary, the complement system acts in the first few minutes, hours, and days to
      control this poxviral infection until the adaptive immune response can react, and
      loss of this system results in lethal infection.

PMID- 19112491
TI  - Ion channel clustering at the axon initial segment and node of Ranvier evolved
      sequentially in early chordates.
AB  - In many mammalian neurons, dense clusters of ion channels at the axonal initial
      segment and nodes of Ranvier underlie action potential generation and rapid
      conduction. Axonal clustering of mammalian voltage-gated sodium and KCNQ (Kv7)
      potassium channels is based on linkage to the actin-spectrin cytoskeleton, which
      is mediated by the adaptor protein ankyrin-G. We identified key steps in the
      evolution of this axonal channel clustering. The anchor motif for sodium channel
      clustering evolved early in the chordate lineage before the divergence of the
      wormlike cephalochordate, amphioxus. Axons of the lamprey, a very primitive
      vertebrate, exhibited some invertebrate features (lack of myelin, use of giant
      diameter to hasten conduction), but possessed narrow initial segments bearing
      sodium channel clusters like in more recently evolved vertebrates. The KCNQ
      potassium channel anchor motif evolved after the divergence of lampreys from
      other vertebrates, in a common ancestor of shark and humans. Thus, clustering of
      voltage-gated sodium channels was a pivotal early innovation of the chordates.
      Sodium channel clusters at the axon initial segment serving the generation of
      action potentials evolved long before the node of Ranvier. KCNQ channels acquired
      anchors allowing their integration into pre-existing sodium channel complexes at
      about the same time that ancient vertebrates acquired myelin, saltatory
      conduction, and hinged jaws. The early chordate refinements in action potential
      mechanisms we have elucidated appear essential to the complex neural signaling,
      active behavior, and evolutionary success of vertebrates.

PMID- 19112492
TI  - Regulated nuclear trafficking of rpL10A mediated by NIK1 represents a defense
      strategy of plant cells against virus.
AB  - The NSP-interacting kinase (NIK) receptor-mediated defense pathway has been
      identified recently as a virulence target of the geminivirus nuclear shuttle
      protein (NSP). However, the NIK1-NSP interaction does not fit into the elicitor
      receptor model of resistance, and hence the molecular mechanism that links this
      antiviral response to receptor activation remains obscure. Here, we identified a
      ribosomal protein, rpL10A, as a specific partner and substrate of NIK1 that
      functions as an immediate downstream effector of NIK1-mediated response.
      Phosphorylation of cytosolic rpL10A by NIK1 redirects the protein to the nucleus
      where it may act to modulate viral infection. While ectopic expression of normal
      NIK1 or a hyperactive NIK1 mutant promotes the accumulation of phosphorylated
      rpL10A within the nuclei, an inactive NIK1 mutant fails to redirect the protein
      to the nuclei of co-transfected cells. Likewise, a mutant rpL10A defective for
      NIK1 phosphorylation is not redirected to the nucleus. Furthermore, loss of
      rpL10A function enhances susceptibility to geminivirus infection, resembling the
      phenotype of nik1 null alleles. We also provide evidence that geminivirus
      infection directly interferes with NIK1-mediated nuclear relocalization of rpL10A
      as a counterdefensive measure. However, the NIK1-mediated defense signaling
      neither activates RNA silencing nor promotes a hypersensitive response but
      inhibits plant growth and development. Although the virulence function of the
      particular geminivirus NSP studied here overcomes this layer of defense in
      Arabidopsis, the NIK1-mediated signaling response may be involved in restricting
      the host range of other viruses.

PMID- 19112493
TI  - Independent regulation of reovirus membrane penetration and apoptosis by the mu1
      phi domain.
AB  - Apoptosis plays an important role in the pathogenesis of reovirus encephalitis.
      Reovirus outer-capsid protein mu1, which functions to penetrate host cell
      membranes during viral entry, is the primary regulator of apoptosis following
      reovirus infection. Ectopic expression of full-length and truncated forms of mu1
      indicates that the mu1 phi domain is sufficient to elicit a cell death response.
      To evaluate the contribution of the mu1 phi domain to the induction of apoptosis
      following reovirus infection, phi mutant viruses were generated by reverse
      genetics and analyzed for the capacity to penetrate cell membranes and elicit
      apoptosis. We found that mutations in phi diminish reovirus membrane penetration
      efficiency by preventing conformational changes that lead to generation of key
      reovirus entry intermediates. Independent of effects on membrane penetration,
      amino acid substitutions in phi affect the apoptotic potential of reovirus,
      suggesting that phi initiates apoptosis subsequent to cytosolic delivery. In
      comparison to wild-type virus, apoptosis-defective phi mutant viruses display
      diminished neurovirulence following intracranial inoculation of newborn mice.
      These results indicate that the phi domain of mu1 plays an important regulatory
      role in reovirus-induced apoptosis and disease.

PMID- 19112495
TI  - The Staphylococcus aureus protein Sbi acts as a complement inhibitor and forms a
      tripartite complex with host complement Factor H and C3b.
AB  - The Gram-positive bacterium Staphylococcus aureus, similar to other pathogens,
      binds human complement regulators Factor H and Factor H related protein 1 (FHR-1)
      from human serum. Here we identify the secreted protein Sbi (Staphylococcus
      aureus binder of IgG) as a ligand that interacts with Factor H by a-to our
      knowledge-new type of interaction. Factor H binds to Sbi in combination with C3b
      or C3d, and forms tripartite SbiratioC3ratioFactor H complexes. Apparently, the
      type of C3 influences the stability of the complex; surface plasmon resonance
      studies revealed a higher stability of C3d complexed to Sbi, as compared to C3b
      or C3. As part of this tripartite complex, Factor H is functionally active and
      displays complement regulatory activity. Sbi, by recruiting Factor H and C3b,
      acts as a potent complement inhibitor, and inhibits alternative pathway-mediated
      lyses of rabbit erythrocytes by human serum and sera of other species. Thus, Sbi
      is a multifunctional bacterial protein, which binds host complement components
      Factor H and C3 as well as IgG and beta(2)-glycoprotein I and interferes with
      innate immune recognition.

PMID- 19112494
TI  - The Golgin GMAP210/TRIP11 anchors IFT20 to the Golgi complex.
AB  - Eukaryotic cells often use proteins localized to the ciliary membrane to monitor
      the extracellular environment. The mechanism by which proteins are sorted,
      specifically to this subdomain of the plasma membrane, is almost completely
      unknown. Previously, we showed that the IFT20 subunit of the intraflagellar
      transport particle is localized to the Golgi complex, in addition to the cilium
      and centrosome, and hypothesized that the Golgi pool of IFT20 plays a role in
      sorting proteins to the ciliary membrane. Here, we show that IFT20 is anchored to
      the Golgi complex by the golgin protein GMAP210/Trip11. Mice lacking GMAP210 die
      at birth with a pleiotropic phenotype that includes growth restriction,
      ventricular septal defects of the heart, omphalocele, and lung hypoplasia. Cells
      lacking GMAP210 have normal Golgi structure, but IFT20 is no longer localized to
      this organelle. GMAP210 is not absolutely required for ciliary assembly, but
      cilia on GMAP210 mutant cells are shorter than normal and have reduced amounts of
      the membrane protein polycystin-2 localized to them. This work suggests that
      GMAP210 and IFT20 function together at the Golgi in the sorting or transport of
      proteins destined for the ciliary membrane.

PMID- 19112496
TI  - High risk of severe anaemia after chlorproguanil-dapsone+artesunate antimalarial
      treatment in patients with G6PD (A-) deficiency.
AB  - BACKGROUND: Glucose-6-phosphate dehydrogenase (G6PD) deficiency is the most
      common inherited human enzyme defect. This deficiency provides some protection
      from clinical malaria, but it can also cause haemolysis after administration of
      drugs with oxidant properties. METHODS: The safety of chlorproguanil
      dapsone+artesunate (CD+A) and amodiaquine+sulphadoxine-pyrimethamine (AQ+SP) for
      the treatment of uncomplicated P. falciparum malaria was evaluated according to
      G6PD deficiency in a secondary analysis of an open-label, randomized clinical
      trial. 702 children, treated with CD+A or AQ+SP and followed for 28 days after
      treatment were genotyped for G6PD A- deficiency. FINDINGS: In the first 4 days
      following CD+A treatment, mean haematocrit declined on average 1.94% (95% CI 1.54
      to 2.33) and 1.05% per day (95% CI 0.95 to 1.15) respectively in patients with
      G6PD deficiency and normal patients; a mean reduction of 1.3% per day was
      observed among patients who received AQ+SP regardless of G6PD status (95% CI 1.25
      to 1.45). Patients with G6PD deficiency recipients of CD+A had significantly
      lower haematocrit than the other groups until day 7 (p = 0.04). In total, 10
      patients had severe post-treatment haemolysis requiring blood transfusion.
      Patients with G6PD deficiency showed a higher risk of severe anaemia following
      treatment with CD+A (RR = 10.2; 95% CI 1.8 to 59.3) or AQ+SP (RR = 5.6; 95% CI
      1.0 to 32.7). CONCLUSIONS: CD+A showed a poor safety profile in individuals with
      G6PD deficiency most likely as a result of dapsone induced haemolysis. Screening
      for G6PD deficiency before drug administration of potentially pro-oxidants drugs,
      like dapsone-containing combinations, although seldom available, is necessary.

PMID- 19112497
TI  - TRAF6 autoubiquitination-independent activation of the NFkappaB and MAPK pathways
      in response to IL-1 and RANKL.
AB  - The adapter protein TRAF6 is critical for mediating signal transduction from
      members of the IL-1R/TLR and TNFR superfamilies. The TRAF6 RING finger domain
      functions as an ubiquitin E3 ligase capable of generating non-degradative K63
      linked ubiquitin chains. It is believed that these chains serve as docking sites
      for formation of signaling complexes, and that K63-linked autoubiquitination of
      TRAF6 is essential for formation and activation of a complex involving the kinase
      TAK1 and its adapters, TAB1 and TAB2. In order to assess independently the E3
      ligase and ubiquitin substrate functions of TRAF6, we generated, respectively,
      RING domain and complete lysine-deficient TRAF6 mutants. We found that while the
      TRAF6 RING domain is required for activation of TAK1, it is dispensable for
      interaction between TRAF6 and the TAK1-TAB1-TAB2 complex. Likewise, lysine
      deficient TRAF6 was found to interact with the TAK1-TAB1-TAB2 complex, but
      surprisingly was also found to be fully competent to activate TAK1, as well as
      NFkappaB and AP-1 reporters. Furthermore, lysine-deficient TRAF6 rescued IL-1
      mediated NFkappaB and MAPK activation, as well as IL-6 elaboration in
      retrovirally-rescued TRAF6-deficient fibroblasts. Lysine-deficient TRAF6 also
      rescued RANKL-mediated NFkappaB and MAPK activation, and osteoclastogenesis in
      retrovirally-rescued TRAF6-deficient bone marrow macrophages. While incapable of
      being ubiquitinated itself, we demonstrate that lysine-deficient TRAF6 remains
      competent to induce ubiquitination of IKKgamma/NEMO. Further, this NEMO
      modification contributes to TRAF6-mediated activation of NFkappaB. Collectively,
      our results suggest that while TRAF6 autoubiquitination may serve as a marker of
      activation, it is unlikely to underpin RING finger-dependent TRAF6 function.

PMID- 19112498
TI  - Myocardial hypertrophy overrides the angiogenic response to hypoxia.
AB  - BACKGROUND: Cyanosis and myocardial hypertrophy frequently occur in combination.
      Hypoxia or cyanosis can be potent inducers of angiogenesis, regulating the
      expression of hypoxia-inducible factors (HIF), vascular endothelial growth
      factors (VEGF), and VEGF receptors (VEGFR-1 and 2); in contrast, pressure
      overload hypertrophy is often associated with impaired pro-angiogenic signaling
      and decreased myocardial capillary density. We hypothesized that the
      physiological pro-angiogenic response to cyanosis in the hypertrophied myocardium
      is blunted through differential HIF and VEGF-associated signaling. METHODS AND
      RESULTS: Newborn rabbits underwent aortic banding and, together with sham
      operated littermates, were transferred into a hypoxic chamber (FiO(2) = 0.12) at
      3 weeks of age. Control banded or sham-operated rabbits were housed in normoxia.
      Systemic cyanosis was confirmed (hematocrit, arterial oxygen saturation, and
      serum erythropoietin). Myocardial tissue was assayed for low oxygen
      concentrations using a pimonidazole adduct. At 4 weeks of age, HIF-1alpha and HIF
      2alpha protein levels, HIF-1alpha DNA-binding activity, and expression of VEGFR
      1, VEGFR-2, and VEGF were determined in hypoxic and normoxic rabbits. At 6 weeks
      of age, left-ventricular capillary density was assessed by immunohistochemistry.
      Under normoxia, capillary density was decreased in the banded rabbits compared to
      non-banded littermates. As expected, non-hypertrophied hearts responded to
      hypoxia with increased capillary density; however, banded hypoxic rabbits
      demonstrated no increase in angiogenesis. This blunted pro-angiogenic response to
      hypoxia in the hypertrophied myocardium was associated with lower HIF-2alpha and
      VEGFR-2 levels and increased HIF-1alpha activity and VEGFR-1 expression. In
      contrast, non-hypertrophied hearts responded to hypoxia with increased HIF-2alpha
      and VEGFR-2 expression with lower VEGFR-1 expression. CONCLUSION: The
      participation of HIF-2alpha and VEGFR-2 appear to be required for hypoxia
      stimulated myocardial angiogenesis. In infant rabbit hearts with pressure
      overload hypertrophy, this pro-angiogenic response to hypoxia is effectively
      uncoupled, apparently in part due to altered HIF-mediated signaling and VEGFR
      subtype expression.

PMID- 19112499
TI  - Compositional genome contexts affect gene expression control in sea urchin
      embryo.
AB  - Gene expression is widely perceived as exclusively controlled by the information
      contained in cis-regulatory regions. These are built in a modular way, each
      module being a cluster of binding sites for the transcription factors that
      control the level, the location and the time at which gene transcription takes
      place. On the other hand, results from our laboratory have shown that gene
      expression is affected by the compositional properties (GC levels) of the
      isochores in which genes are embedded, i.e. the genome context. To clarify how
      compositional genomic properties affect the way cis-regulatory information is
      utilized, we have changed the genome context of a GFP-reporter gene containing
      the complete cis-regulatory region of the gene spdeadringer (spdri), expressed
      during sea urchin embryogenesis. We have observed that GC levels higher or lower
      than those found in the natural genome context can alter the reporter expression
      pattern. We explain this as the result of an interference with the functionality
      of specific modules in the gene's cis-regulatory region. From these observations
      we derive the notion that the compositional properties of the genome context can
      affect cis-regulatory control of gene expression. Therefore although the way a
      gene works depends on the information contained in its cis-regulatory region,
      availability of such information depends on the compositional properties of the
      genomic context.

PMID- 19112500
TI  - Chromosomal inversions between human and chimpanzee lineages caused by
      retrotransposons.
AB  - The long interspersed element-1 (LINE-1 or L1) and Alu elements are the most
      abundant mobile elements comprising 21% and 11% of the human genome,
      respectively. Since the divergence of human and chimpanzee lineages, these
      elements have vigorously created chromosomal rearrangements causing genomic
      difference between humans and chimpanzees by either increasing or decreasing the
      size of genome. Here, we report an exotic mechanism, retrotransposon
      recombination-mediated inversion (RRMI), that usually does not alter the amount
      of genomic material present. Through the comparison of the human and chimpanzee
      draft genome sequences, we identified 252 inversions whose respective inversion
      junctions can clearly be characterized. Our results suggest that L1 and Alu
      elements cause chromosomal inversions by either forming a secondary structure or
      providing a fragile site for double-strand breaks. The detailed analysis of the
      inversion breakpoints showed that L1 and Alu elements are responsible for at
      least 44% of the 252 inversion loci between human and chimpanzee lineages,
      including 49 RRMI loci. Among them, three RRMI loci inverted exonic regions in
      known genes, which implicates this mechanism in generating the genomic and
      phenotypic differences between human and chimpanzee lineages. This study is the
      first comprehensive analysis of mobile element bases inversion breakpoints
      between human and chimpanzee lineages, and highlights their role in primate
      genome evolution.

PMID- 19112501
TI  - The impact of different antibiotic regimens on the emergence of antimicrobial
      resistant bacteria.
AB  - BACKGROUND: The emergence and ongoing spread of antimicrobial-resistant bacteria
      is a major public health threat. Infections caused by antimicrobial-resistant
      bacteria are associated with substantially higher rates of morbidity and
      mortality compared to infections caused by antimicrobial-susceptible bacteria.
      The emergence and spread of these bacteria is complex and requires incorporating
      numerous interrelated factors which clinical studies cannot adequately address.
      METHODS/PRINCIPAL FINDINGS: A model is created which incorporates several key
      factors contributing to the emergence and spread of resistant bacteria including
      the effects of the immune system, acquisition of resistance genes and
      antimicrobial exposure. The model identifies key strategies which would limit the
      emergence of antimicrobial-resistant bacterial strains. Specifically, the
      simulations show that early initiation of antimicrobial therapy and combination
      therapy with two antibiotics prevents the emergence of resistant bacteria,
      whereas shorter courses of therapy and sequential administration of antibiotics
      promote the emergence of resistant strains. CONCLUSIONS/SIGNIFICANCE: The
      principal findings suggest that (i) shorter lengths of antibiotic therapy and
      early interruption of antibiotic therapy provide an advantage for the resistant
      strains, (ii) combination therapy with two antibiotics prevents the emergence of
      resistance strains in contrast to sequential antibiotic therapy, and (iii) early
      initiation of antibiotics is among the most important factors preventing the
      emergence of resistant strains. These findings provide new insights into
      strategies aimed at optimizing the administration of antimicrobials for the
      treatment of infections and the prevention of the emergence of antimicrobial
      resistance.

PMID- 19112502
TI  - The effects of aging on researchers' publication and citation patterns.
AB  - The average age at which U.S. researchers receive their first grant from NIH has
      increased from 34.3 in 1970, to 41.7 in 2004. These data raise the crucial
      question of the effects of aging on the scientific productivity and impact of
      researchers. Drawing on a sizeable sample of 6,388 university professors in
      Quebec who have published at least one paper between 2000 and 2007, our results
      identify two turning points in the professors' careers. A first turning point is
      visible at age 40 years, where researchers start to rely on older literature and
      where their productivity increases at a slower pace--after having increased
      sharply since the beginning of their career. A second turning point can be seen
      around age 50, when researchers are the most productive whereas their average
      scientific impact is at its lowest. Our results also show that older professors
      publish fewer first-authored papers and move closer to the end of the list of co
      authors. Although average scientific impact per paper decreases linearly until
      about age 50, the average number of papers in highly cited journals and among
      highly cited papers rises continuously until retirement. Our results show clearly
      that productivity and impact are not a simple and declining function of age and
      that we must take into account the collaborative aspects of scientific research.
      Science is a collective endeavor and, as our data shows, researchers of all ages
      play a significant role in its dynamic.

PMID- 19112503
TI  - In C. elegans, high levels of dsRNA allow RNAi in the absence of RDE-4.
AB  - C. elegans Dicer requires an accessory double-stranded RNA binding protein, RDE
      4, to enact the first step of RNA interference, the cleavage of dsRNA to produce
      siRNA. While RDE-4 is typically essential for RNAi, we report that in the
      presence of high concentrations of trigger dsRNA, rde-4 deficient animals are
      capable of silencing a transgene. By multiple criteria the silencing occurs by
      the canonical RNAi pathway. For example, silencing is RDE-1 dependent and
      exhibits a decrease in the targeted mRNA in response to an increase in siRNA. We
      also find that high concentrations of dsRNA trigger lead to increased
      accumulation of primary siRNAs, consistent with the existence of a rate-limiting
      step during the conversion of primary to secondary siRNAs. Our studies also
      revealed that transgene silencing occurs at low levels in the soma, even in the
      presence of ADARs, and that at least some siRNAs accumulate in a temperature
      dependent manner. We conclude that an RNAi response varies with different
      conditions, and this may allow an organism to tailor a response to specific
      environmental signals.

PMID- 19112505
TI  - Reduction of Orc6 expression sensitizes human colon cancer cells to 5
      fluorouracil and cisplatin.
AB  - Previous studies from our group have shown that the expression levels of Orc6
      were highly elevated in colorectal cancer patient specimens and the induction of
      Orc6 was associated with 5-fluorouracil (5-FU) treatment. The goal of this study
      was to investigate the molecular and cellular impact of Orc6 in colon cancer. In
      this study, we use HCT116 (wt-p53) and HCT116 (null-p53) colon cancer cell lines
      as a model system to investigate the impact of Orc6 on cell proliferation,
      chemosensitivity and pathways involved with Orc6. We demonstrated that the down
      regulation of Orc6 sensitizes colon cancer cells to both 5-FU and cisplatin (cis
      pt) treatment. Decreased Orc6 expression in HCT-116 (wt-p53) cells by RNA
      interference triggered cell cycle arrest at G1 phase. Prolonged inhibition of
      Orc6 expression resulted in multinucleated cells in HCT-116 (wt-p53) cell line.
      Western immunoblot analysis showed that down regulation of Orc6 induced p21
      expression in HCT-116 (wt-p53) cells. The induction of p21 was mediated by
      increased level of phosphorylated p53 at ser-15. By contrast, there is no
      elevated expression of p21 in HCT-116 (null-p53) cells. Orc6 down regulation also
      increased the expression of DNA damaging repair protein GADD45beta and reduced
      the expression level of JNK1. Orc6 may be a potential novel target for future
      anti cancer therapeutic development in colon cancer.

PMID- 19112504
TI  - HIV-1 infection of bone marrow hematopoietic progenitor cells and their role in
      trafficking and viral dissemination.
AB  - Patients with HIV-1 often present with a wide range of hematopoietic
      abnormalities, some of which may be due to the presence of opportunistic
      infections and to therapeutic drug treatments. However, many of these
      abnormalities are directly related to HIV-1 replication in the bone marrow (BM).
      Although the most primitive hematopoietic progenitor cells (HPCs) are resistant
      to HIV-1 infection, once these cells begin to differentiate and become committed
      HPCs they become increasingly susceptible to HIV-1 infection and permissive to
      viral gene expression and infectious virus production. Trafficking of BM-derived
      HIV-1-infected monocytes has been shown to be involved in the dissemination of
      HIV-1 into the central nervous system (CNS), and it is possible that HIV-1
      replication in the BM and infection of BM HPCs may be involved in the early steps
      leading to the development of HIV-1-associated dementia (HAD) as an end result of
      this cellular trafficking process. In addition, the growth and development of
      HPCs in the BM of patients with HIV-1 has also been shown to be impaired due to
      the presence of HIV-1 proteins and changes in the cytokine milieu, potentially
      leading to an altered maturation process and to increased cell death within one
      or more BM cell lineages. Changes in the growth and differentiation process of
      HPCs may be involved in the generation of monocyte populations that are more
      susceptible and/or permissive to HIV-1, and have potentially altered trafficking
      profiles to several organs, including the CNS. A monocyte subpopulation with
      these features has been shown to expand during the course of HIV-1 disease,
      particularly in HAD patients, and is characterized by low CD14 expression and the
      presence of cell surface CD16.

PMID- 19112506
TI  - Genome-wide co-expression analysis in multiple tissues.
AB  - Expression quantitative trait loci (eQTLs) represent genetic control points of
      gene expression, and can be categorized as cis- and trans-acting, reflecting
      local and distant regulation of gene expression respectively. Although there is
      evidence of co-regulation within clusters of trans-eQTLs, the extent of co
      expression patterns and their relationship with the genotypes at eQTLs are not
      fully understood. We have mapped thousands of cis- and trans-eQTLs in four
      tissues (fat, kidney, adrenal and left ventricle) in a large panel of rat
      recombinant inbred (RI) strains. Here we investigate the genome-wide correlation
      structure in expression levels of eQTL transcripts and underlying genotypes to
      elucidate the nature of co-regulation within cis- and trans-eQTL datasets. Across
      the four tissues, we consistently found statistically significant correlations of
      cis-regulated gene expression to be rare (<0.9% of all pairs tested). Most (>80%)
      of the observed significant correlations of cis-regulated gene expression are
      explained by correlation of the underlying genotypes. In comparison, co
      expression of trans-regulated gene expression is more common, with significant
      correlation ranging from 2.9%-14.9% of all pairs of trans-eQTL transcripts. We
      observed a total of 81 trans-eQTL clusters (hot-spots), defined as consisting of
      > or =10 eQTLs linked to a common region, with very high levels of correlation
      between trans-regulated transcripts (77.2-90.2%). Moreover, functional analysis
      of large trans-eQTL clusters (> or =30 eQTLs) revealed significant functional
      enrichment among genes comprising 80% of the large clusters. The results of this
      genome-wide co-expression study show the effects of the eQTL genotypes on the
      observed patterns of correlation, and suggest that functional relatedness between
      genes underlying trans-eQTLs is reflected in the degree of co-expression observed
      in trans-eQTL clusters. Our results demonstrate the power of an integrative,
      systematic approach to the analysis of a large gene expression dataset to uncover
      underlying structure, and inform future eQTL studies.

PMID- 19112507
TI  - Optic flow stimuli in and near the visual field centre: a group FMRI study of
      motion sensitive regions.
AB  - Motion stimuli in one visual hemifield activate human primary visual areas of the
      contralateral side, but suppress activity of the corresponding ipsilateral
      regions. While hemifield motion is rare in everyday life, motion in both
      hemifields occurs regularly whenever we move. Consequently, during motion primary
      visual regions should simultaneously receive excitatory and inhibitory inputs. A
      comparison of primary and higher visual cortex activations induced by bilateral
      and unilateral motion stimuli is missing up to now. Many motion studies focused
      on the MT+ complex in the parieto-occipito-temporal cortex. In single human
      subjects MT+ has been subdivided in area MT, which was activated by motion
      stimuli in the contralateral visual field, and area MST, which responded to
      motion in both the contra- and ipsilateral field. In this study we investigated
      the cortical activation when excitatory and inhibitory inputs interfere with each
      other in primary visual regions and we present for the first time group results
      of the MT+ subregions, allowing for comparisons with the group results of other
      motion processing studies. Using functional magnetic resonance imaging (fMRI), we
      investigated whole brain activations in a large group of healthy humans by
      applying optic flow stimuli in and near the visual field centre and performed a
      second level analysis. Primary visual areas were activated exclusively by motion
      in the contralateral field but to our surprise not by central flow fields.
      Inhibitory inputs to primary visual regions appear to cancel simultaneously
      occurring excitatory inputs during central flow field stimulation. Within MT+ we
      identified two subregions. Putative area MST (pMST) was activated by ipsi- and
      contralateral stimulation and located in the anterior part of MT+. The second
      subregion was located in the more posterior part of MT+ (putative area MT, pMT).

PMID- 19112508
TI  - Asthma is inversely associated with Helicobacter pylori status in an urban
      population.
AB  - BACKGROUND: Microbial exposures have been suggested to confer protection from
      allergic disorders and reduced exposures to gastrointestinal microbiota have been
      proposed as an explanation for the increase in asthma prevalence. Since the
      general prevalence of Helicobacter pylori has been decreasing, we hypothesized
      that H. pylori serostatus would be inversely related to the presence of asthma.
      METHODS: Adults were recruited to participate in the New York University
      (NYU)/Bellevue Asthma Registry in New York City. Adult asthma cases (N = 318) and
      controls (N = 208) were identified and serum IgG antibodies to H. pylori whole
      cell antigens or the immunodominant CagA antigen were measured. RESULTS: As
      expected, the asthma cases and controls differed with respect to atopy and lung
      function. Seropositivity to H. pylori or CagA antigen was present in 47.1% of the
      total case and control study population. Asthma was inversely associated with
      CagA seropositivity (OR = 0.57, 95% CI = 0.36-0.89). Median age of onset of
      asthma (doctor's diagnosis) was older (21 years) among individuals with CagA+
      strains than among H. pylori- individuals (11 years) (p = 0.006). CONCLUSION:
      These data are consistent with the hypothesis that colonization with CagA+ H.
      pylori strains is inversely associated with asthma and is associated with an
      older age of asthma onset in an urban population. The data suggest H. pylori as a
      marker for protection.

PMID- 19112509
TI  - BMP-7 does not protect against bleomycin-induced lung or skin fibrosis.
AB  - Bone morphogenic protein (BMP)-7 is a member of the BMP family which are
      structurally and functionally related, and part of the TGFbeta super family of
      growth factors. BMP-7 has been reported to inhibit renal fibrosis and TGFbeta1
      induced epithelial-mesenchymal transition (EMT), in part through negative
      interactions with TGFbeta1 induced Smad 2/3 activation. We utilized in vivo
      bleomycin-induced fibrosis models in the skin and lung to determine the potential
      therapeutic effect of BMP-7. We then determined the effect of BMP-7 on TGFbeta1
      induced EMT in lung epithelial cells and collagen production by human lung
      fibroblasts. We show that BMP-7 did not affect bleomycin-induced fibrosis in
      either the lung or skin in vivo; had no effect on expression of pro-fibrotic
      genes by human lung fibroblasts, either at rest or following exposure to
      TGFbeta1; and did not modulate TGFbeta1-induced EMT in human lung epithelial
      cells. Taken together our data indicates that BMP-7 has no anti-fibrotic effect
      in lung or skin fibrosis either in vivo or in vitro. This suggests that the
      therapeutic options for BMP-7 may be confined to the renal compartment.

PMID- 19112510
TI  - Rhabdovirus matrix protein structures reveal a novel mode of self-association.
AB  - The matrix (M) proteins of rhabdoviruses are multifunctional proteins essential
      for virus maturation and budding that also regulate the expression of viral and
      host proteins. We have solved the structures of M from the vesicular stomatitis
      virus serotype New Jersey (genus: Vesiculovirus) and from Lagos bat virus (genus:
      Lyssavirus), revealing that both share a common fold despite sharing no
      identifiable sequence homology. Strikingly, in both structures a stretch of
      residues from the otherwise-disordered N terminus of a crystallographically
      adjacent molecule is observed binding to a hydrophobic cavity on the surface of
      the protein, thereby forming non-covalent linear polymers of M in the crystals.
      While the overall topology of the interaction is conserved between the two
      structures, the molecular details of the interactions are completely different.
      The observed interactions provide a compelling model for the flexible self
      assembly of the matrix protein during virion morphogenesis and may also modulate
      interactions with host proteins.

PMID- 19112511
TI  - Sex-differential effect on infant mortality of oral polio vaccine administered
      with BCG at birth in Guinea-Bissau. A natural experiment.
AB  - BACKGROUND: The policy to provide oral polio vaccine (OPV) at birth was
      introduced in low-income countries to increase coverage. The effect of OPV at
      birth on overall child mortality was never studied. During a trial of vitamin A
      supplementation (VAS) at birth in Guinea-Bissau, OPV was not available during
      several periods. We took advantage of this "natural experiment" to test the
      effect on mortality of receiving OPV at birth. METHODOLOGY: Between 2002 and
      2004, the VAS trial randomised normal-birth-weight infants to 50,000 IU VAS or
      placebo administered with BCG. Provision of OPV at birth was not part of the
      trial, but we noted whether the infants received OPV or not. OPV was missing
      during several periods in 2004. We used Cox proportional hazards models to
      compute mortality rate ratios (MRR) of children who had received or not received
      OPV at birth. PRINCIPAL FINDINGS: A total of 962 (22.1%) of the 4345 enrolled
      children did not receive OPV at birth; 179 children died within the first year of
      life. Missing OPV at birth was associated with a tendency for decreased mortality
      (adjusted MRR = 0.69 (95% CI = 0.46-1.03)), the effect being similar among
      recipients of VAS and placebo. There was a highly significant interaction between
      OPV at birth and sex (p = 0.006). Not receiving OPV at birth was associated with
      a weak tendency for increased mortality in girls (1.14 (0.70-1.89)) but
      significantly decreased mortality in boys (0.35 (0.18-0.71)). CONCLUSIONS: In our
      study OPV at birth had a sex-differential effect on mortality. Poliovirus is
      almost eradicated and OPV at birth contributes little to herd immunity. A
      randomised study of the effect of OPV at birth on overall mortality in both sexes
      is warranted.

PMID- 19112512
TI  - Is replication the gold standard for validating genome-wide association findings?
AB  - With the advent of genome-wide association (GWA) studies, researchers are hoping
      that reliable genetic association of common human complex diseases/traits can be
      detected. Currently, there is an increasing enthusiasm about GWA and a number of
      GWA studies have been published. In the field a common practice is that
      replication should be used as the gold standard to validate an association
      finding. In this article, based on empirical and theoretical data, we emphasize
      that replication of GWA findings can be quite difficult, and should not always be
      expected, even when true variants are identified. The probability of replication
      becomes smaller with the increasing number of independent GWA studies if the
      power of individual replication studies is less than 100% (which is usually the
      case), and even a finding that is replicated may not necessarily be true. We
      argue that the field may have unreasonably high expectations on success of
      replication. We also wish to raise the question whether it is sufficient or
      necessary to treat replication as the ultimate and gold standard for defining
      true variants. We finally discuss the usefulness of integrating evidence from
      multiple levels/sources such as genetic epidemiological studies (at the DNA
      level), gene expression studies (at the RNA level), proteomics (at the protein
      level), and follow-up molecular and cellular studies for eventual validation and
      illumination of the functional relevance of the genes uncovered.

PMID- 19112513
TI  - Safety, humoral and cell mediated immune responses to two formulations of an
      inactivated, split-virion influenza A/H5N1 vaccine in children.
AB  - BACKGROUND: Highly pathogenic influenza A/H5N1 has caused outbreaks in wild birds
      and poultry in Asia, Africa and Europe. It has also infected people, especially
      children, causing severe illness and death. Although the virus shows limited
      ability to transmit between humans, A/H5N1 represents a potential source of the
      next influenza pandemic. This study assesses the safety and immunogenicity of
      aluminium hydroxide adjuvanted (Al) and non adjuvanted influenza
      A/Vietnam/1194/2004 NIBRG-14 (H5N1) vaccine in children. METHODS AND FINDINGS: In
      a Phase II, open, randomised, multicentre trial 180 children aged 6 months to 17
      years received two injections, 21 days apart, of vaccine containing either: 30
      microg haemagglutinin (HA) with adjuvant (30 microg+Al) or 7.5 microg HA without
      adjuvant. An additional 60 children aged 6-35 months received two "half dose"
      injections (ie 15 microg+Al or 3.8 microg). Safety was followed for 21 days after
      vaccination. Antibody responses were assessed 21 days after each injection and
      cellular immune responses were explored. Vaccination appeared well tolerated in
      all age groups. The 30 microg+Al formulation was more immunogenic than 7.5 microg
      in all age groups: in these two groups 79% and 46% had haemagglutinination
      inhibition antibody titres > or =32 (1/dil). Among 6-35 month-olds, the full
      doses were more immunogenic than their half dose equivalents. Vaccination induced
      a predominantly Th2 response against H5 HA. CONCLUSIONS: This influenza A(H5N1)
      vaccine was well tolerated and immunogenic in children and infants, with Al
      adjuvant providing a clear immunogenic advantage. These results demonstrate that
      an H5N1 Al-adjuvanted vaccine, previously shown to be immunogenic and safe in
      adults, can also be used in children, the group most at risk for pandemic
      influenza.

PMID- 19112514
TI  - Angiogenesis-related gene expression profile with independent prognostic value in
      advanced ovarian carcinoma.
AB  - BACKGROUND: Ovarian carcinoma is the most important cause of gynecological cancer
      related mortality in Western societies. Despite the improved median overall
      survival in patients receiving chemotherapy regimens such as paclitaxel and
      carboplatin combination, relapse still occurs in most advanced diseased patients.
      Increased angiogenesis is associated with rapid recurrence and decreased survival
      in ovarian cancer. This study was planned to identify an angiogenesis-related
      gene expression profile with prognostic value in advanced ovarian carcinoma
      patients. METHODOLOGY/PRINCIPAL FINDINGS: RNAs were collected from formalin-fixed
      paraffin-embedded samples of 61 patients with III/IV FIGO stage ovarian cancer
      who underwent surgical cytoreduction and received a carboplatin plus paclitaxel
      regimen. Expression levels of 82 angiogenesis related genes were measured by
      quantitative real-time polymerase chain reaction using TaqMan low-density arrays.
      A 34-gene-profile which was able to predict the overall survival of ovarian
      carcinoma patients was identified. After a leave-one-out cross validation, the
      profile distinguished two groups of patients with different outcomes. Median
      overall survival and progression-free survival for the high risk group was 28.3
      and 15.0 months, respectively, and was not reached by patients in the low risk
      group at the end of follow-up. Moreover, the profile maintained an independent
      prognostic value in the multivariate analysis. The hazard ratio for death was 2.3
      (95% CI, 1.5 to 3.2; p<0.001). CONCLUSIONS/SIGNIFICANCE: It is possible to
      generate a prognostic model for advanced ovarian carcinoma based on angiogenesis
      related genes using formalin-fixed paraffin-embedded samples. The present results
      are consistent with the increasing weight of angiogenesis genes in the prognosis
      of ovarian carcinoma.

PMID- 19112515
TI  - Antidepressants of the serotonin-antagonist type increase body fat and decrease
      lifespan of adult Caenorhabditis elegans.
AB  - It was recently suggested that specific antidepressants of the serotonin
      antagonist type, namely mianserin and methiothepin, may exert anti-aging
      properties and specifically extend lifespan of the nematode C.elegans by causing
      a state of perceived calorie restriction (Petrascheck M, Ye X, Buck LB: An
      antidepressant that extends lifespan in adult Caenorhabditis elegans; Nature, Nov
      22, 2007;450(7169):553-6, PMID 18033297). Using the same model organism, we
      instead observe a reduction of life expectancy when employing the commonly used,
      standardized agar-based solid-phase assay while applying the same or lower
      concentrations of the same antidepressants. Consistent with a well-known side
      effect of these compounds in humans, antidepressants not only reduced lifespan
      but also increased body fat accumulation in C. elegans reflecting the mammalian
      phenotype. Taken together and in conflict with previously published findings, we
      find that antidepressants of the serotonin-antagonist type not only promote
      obesity, but also decrease nematode lifespan.

PMID- 19112516
TI  - Task-specific codes for face recognition: how they shape the neural
      representation of features for detection and individuation.
AB  - BACKGROUND: The variety of ways in which faces are categorized makes face
      recognition challenging for both synthetic and biological vision systems. Here we
      focus on two face processing tasks, detection and individuation, and explore
      whether differences in task demands lead to differences both in the features most
      effective for automatic recognition and in the featural codes recruited by neural
      processing. METHODOLOGY/PRINCIPAL FINDINGS: Our study appeals to a computational
      framework characterizing the features representing object categories as sets of
      overlapping image fragments. Within this framework, we assess the extent to which
      task-relevant information differs across image fragments. Based on objective
      differences we find among task-specific representations, we test the sensitivity
      of the human visual system to these different face descriptions independently of
      one another. Both behavior and functional magnetic resonance imaging reveal
      effects elicited by objective task-specific levels of information. Behaviorally,
      recognition performance with image fragments improves with increasing task
      specific information carried by different face fragments. Neurally, this
      sensitivity to the two tasks manifests as differential localization of neural
      responses across the ventral visual pathway. Fragments diagnostic for detection
      evoke larger neural responses than non-diagnostic ones in the right posterior
      fusiform gyrus and bilaterally in the inferior occipital gyrus. In contrast,
      fragments diagnostic for individuation evoke larger responses than non-diagnostic
      ones in the anterior inferior temporal gyrus. Finally, for individuation only,
      pattern analysis reveals sensitivity to task-specific information within the
      right "fusiform face area". CONCLUSIONS/SIGNIFICANCE: OUR RESULTS DEMONSTRATE: 1)
      information diagnostic for face detection and individuation is roughly separable;
      2) the human visual system is independently sensitive to both types of
      information; 3) neural responses differ according to the type of task-relevant
      information considered. More generally, these findings provide evidence for the
      computational utility and the neural validity of fragment-based visual
      representation and recognition.

PMID- 19112517
TI  - Focused Attention in Toddlers: Measurement, Stability, and Relations to Negative
      Emotion and Parenting.
AB  - This longitudinal study examined individual differences and correlates of focused
      attention when toddlers were approximately 18 months old (T1; n = 256) and a year
      later (T2; n = 230). Toddlers' attention and negative emotionality were reported
      by mothers and non-parental caregivers and rated globally by observers. Toddlers'
      focused attention also was observed during two mother-child interactions and an
      independent play task. Measures of maternal emotional support and control were
      obtained via self-report and observation. Some contemporaneous relations among
      indices of toddlers' attention were obtained, particularly for observed measures.
      Moreover, all measures of attention demonstrated stability across time. Negative
      emotionality was negatively related to toddlers' observed attention at both ages,
      whereas maternal praise had positive concurrent associations. Maternal control
      was negatively related to observed observed attention at T2 and also predicted
      longitudinally, but only for children who initially had low or moderate
      attention. The findings suggest that individual differences in focused attention
      evidence stability early in life but can be influenced by adult socialization.

PMID- 19112518
TI  - Preparation of PbS Nanoparticles by Phase-Transfer Method and Application to Pb
      Selective Electrode Based on PVC Membrane.
AB  - A novel approach to prepare homogeneous PbS nanoparticles by phase-transfer
      method was developed. The preparatory conditions were studied in detail, and the
      nanoparticles were characterized by transmission electron microscopy (TEM) and UV
      vis spectroscopy. Then a novel lead ion-selective electrode of polyvinyl chloride
      (PVC) membrane based on these lead sulfide nanoparticles was prepared, and the
      optimum ratio of components in the membrane was determined. The results indicated
      that the sensor exhibited a wide concentration range of 1.0x10(-5) to 1.0x10(-2)
      mol.L(-1). The response time of the electrode was about 10 s, and the optimal pH
      in which the electrode could be used was from 3.0 to 7.0. Selectivity
      coefficients indicated that the electrode was selective to the primary ion over
      the interfering ion. The electrode can be used for at least 3 months without any
      divergence in potential. It was successfully applied to directly determine lead
      ions in solution and used as an indicator electrode in potentiometric titration
      of lead ions with EDTA.

PMID- 19112519
TI  - Synthesis and Mechanical Wear Studies of Ultra Smooth Nanostructured Diamond
      (USND) Coatings Deposited by Microwave Plasma Chemical Vapor Deposition with
      He/H(2)/CH(4)/N(2) Mixtures.
AB  - Ultra smooth nanostructured diamond (USND) coatings were deposited by microwave
      plasma chemical vapor deposition (MPCVD) technique using He/H(2)/CH(4)/N(2) gas
      mixture. The RMS surface roughness as low as 4 nm (2 micron square area) and
      grain size of 5-6 nm diamond coatings were achieved on medical grade titanium
      alloy. Previously it was demonstrated that the C(2) species in the plasma is
      responsible for the production of nanocrystalline diamond coatings in the
      Ar/H(2)/CH(4) gas mixture. In this work we have found that CN species is
      responsible for the production of USND coatings in He/H(2)/CH(4)/N(2) plasma. It
      was found that diamond coatings deposited with higher CN species concentration
      (normalized by Balmer H(alpha) line) in the plasma produced smoother and highly
      nanostructured diamond coatings. The correlation between CN/H(alpha) ratios with
      the coating roughness and grain size were also confirmed with different set of
      gas flows/plasma parameters. It is suggested that the presence of CN species
      could be responsible for producing nanocrystallinity in the growth of USND
      coatings using He/H(2)/CH(4)/N(2) gas mixture. The RMS roughness of 4 nm and
      grain size of 5-6 nm were calculated from the deposited diamond coatings using
      the gas mixture which produced the highest CN/H(alpha) species in the plasma.
      Wear tests were performed on the OrthoPOD((r)), a six station pin-on-disk
      apparatus with ultra-high molecular weight polyethylene (UHMWPE) pins
      articulating on USND disks and CoCrMo alloy disk. Wear of the UHMWPE was found to
      be lower for the polyethylene on USND than that of polyethylene on CoCrMo alloy.

PMID- 19112520
TI  - 1,2,3,4-Tetrahydro-1,5-naphthyridines and related heterocyclic scaffolds:
      Exploration of suitable chemistry for library development.
AB  - The chemistry of 1,2,3,4-tetrahydro-1,5-naphthyridines and 2,3,4,5-tetrahydro-1H
      pyrido[3,2-b]azepines has been explored with the goal of discovering reactions at
      N1 suitable for library development. Epoxide openings, palladium-catalyzed N
      arylations, DEPBT-promoted acylations, and urea formation through the reaction
      with isocyanates were all successful. The epoxide opening chemistry using
      homochiral epichlorohydrin, with epoxide reclosure and a second nucleophilic
      opening led to the preparation of a small 24-membered library.

PMID- 19112521
TI  - H, C and N resonance assignments of the C-terminal domain of the 43 kDa subunit
      of the chloroplast signal recognition particle.
AB  - We report the assignment of a 109 amino acid C-terminal chromo domain of the
      chloroplast signal recognition particle cpSRP43 subunit. cpSRP43 plays a crucial
      role in the targeting of light harvesting chlorophyll proteins to the thylakoids.

PMID- 19112522
TI  - Occipital-temporal Reduction and Sustained Visual Attention Deficit in Prenatal
      Alcohol Exposed Adults.
AB  - Visual attention problems have been reported in association with prenatal alcohol
      exposure (PAE). With related behavioral data documented in literature, further
      investigation of this PAE effect would benefit from integrating functional and
      anatomical imaging data to ascertain its neurobiological basis. The current study
      investigated the possible functional and anatomical bases for the PAE-related
      visual sustained attention deficit. Functional magnetic resonance imaging (fMRI)
      data were collected while the subjects performed a sustained visual attention
      task. High resolution, three dimensional anatomical images were also collected
      for morphometric evaluation. In the alcohol-affected subjects, we observed a
      significant white and gray matter volume reduction in the occipital-temporal
      area. Meanwhile, their fMRI activations in the same region resided more
      superiorly than that of the controls resulting in reduced activation in the
      ventral occipital-temporal area. The location of this PAE functional abnormality
      approximately matches that of the significant structural reduction. In addition
      to the well documented corpus callosum abnormalities observed in PAE subjects,
      the present results reveal a teratogenic effect on the occipital-temporal area.
      Furthermore, as the occipital-temporal area plays an important role in visual
      attention, the current observation suggests a neurobiological underpinning for
      the PAE related deficit in sustained visual attention.

PMID- 19112523
TI  - Negative Affect and HIV Risk in Alcohol and Other Drug (AOD) Abusing Adolescent
      Offenders.
AB  - Various depressive symptoms have been linked to elevated levels of HIV risk
      across diverse adult populations in multiple studies. However, this link has been
      examined in a much more limited manner among adolescents, despite an exceedingly
      heightened risk of both HIV and negative affect in this age group. To address the
      current lack of clinically pertinent knowledge in this area, we analyzed baseline
      data from 256 male and 107 female inner city, culturally diverse adolescent
      offenders. Relatively "high" and "low" negative affect subgroups were formed by
      conducting a median split on scores from the well-validated depressive affect
      scale of the Millon Adolescent Clinical Inventory (MACI). Compared to the low
      negative affect subgroup, the high negative affect participants reported
      significantly more sexual partners, unprotected sex, and increased susceptibility
      to HIV, as well as more marijuana, cocaine, and alcohol use (all p's < .05).
      Although demonstrating better condom skills, negative affect participants
      reported less favorable attitudes towards using condoms, less knowledge about HIV
      transmission, and lower sexual self-efficacy than non-depressive participants.
      Symptoms of negative affect are therefore of particular concern for adolescents,
      who are at risk not only for generally acknowledged difficulties such as suicide,
      but also for multiple HIV risk factors. The theoretical and applied implications
      of these findings will be discussed.

PMID- 19112524
TI  - Excitability of cortical neurons depends upon a powerful tonic conductance in
      inhibitory networks.
AB  - Layer 4 of the mouse somatosensory (barrel) cortex has a diversity of interneuron
      cell types. Tonic inhibition in other regions is cell type-specific and mediated,
      in part, by delta-subunit containing, extrasynaptic, GABA(A) receptors. We have
      investigated tonic inhibition in LTS cells, a major type of inhibitory neuron,
      and excitatory cells in layer 4 of the mouse barrel cortex using 4,5,6,7
      tetrahydroisothiazolo-[5,4-c]pyridine-3-ol (THIP), a superagonist of these
      receptors. Bath application of 20 uM THIP produced baseline shifts, which
      indicates activation of tonic inhibition of both excitatory and LTS cells. The
      baseline shift was significantly larger in LTS cells. This finding of greater
      induced current in LTS cells was paralleled by a significantly greater increase
      in conductance with THIP application in LTS cells. The increase in conductance
      resulted in LTS cells requiring more current to reach threshold. Because of the
      differential effects of tonic inhibition on LTS cells and excitatory cells, bath
      application of THIP increased the network excitability, measured by multi-unit
      recordings. Thus, the network effect of tonic inhibition in horizontal layer 4
      circuits is a paradoxical increase in excitation.

PMID- 19112525
TI  - Small-Signal Amplification of Period-Doubling Bifurcations in Smooth Iterated
      Maps.
AB  - Various authors have shown that, near the onset of a period-doubling bifurcation,
      small perturbations in the control parameter may result in much larger
      disturbances in the response of the dynamical system. Such amplification of small
      signals can be measured by a gain defined as the magnitude of the disturbance in
      the response divided by the perturbation amplitude. In this paper, the perturbed
      response is studied using normal forms based on the most general assumptions of
      iterated maps. Such an analysis provides a theoretical footing for previous
      experimental and numerical observations, such as the failure of linear analysis
      and the saturation of the gain. Qualitative as well as quantitative features of
      the gain are exhibited using selected models of cardiac dynamics.

PMID- 19112526
TI  - Ultrasound Contrast Agents in the Study of Kidney Function in Health and Disease.
AB  - Ultrasound contrast agents are gas filled microbubbles that enhance the
      ultrasound image. They behave similarly to red blood cells and cross all
      capillary beds; making contrast enhanced ultrasonography (CEU) a suitable
      technique to study vasculature and tissue blood flow. Ultrasound contrast agents
      have been found to be safe after intravenous injection. CEU has been used
      extensively in the field of cardiology. Currently, study of renal vasculature and
      renal blood flow requires complicated, time consuming and expensive techniques,
      which are not commonly used in clinical settings. CEU potentially may serve as a
      relatively noninvasive and safe technique for studying renal hemodynamics in
      health and disease. In this article we have reviewed the literature on the use of
      CEU in the study of kidney disease.

PMID- 19112527
TI  - Censored Median Regression and Profile Empirical Likelihood.
AB  - We implement profile empirical likelihood based inference for censored median
      regression models. Inference for any specified sub-vector is carried out by
      profiling out the nuisance parameters from the "plug-in" empirical likelihood
      ratio function proposed by Qin and Tsao. To obtain the critical value of the
      profile empirical likelihood ratio statistic, we first investigate its asymptotic
      distribution. The limiting distribution is a sum of weighted chi square
      distributions. Unlike for the full empirical likelihood, however, the derived
      asymptotic distribution has intractable covariance structure. Therefore, we
      employ the bootstrap to obtain the critical value, and compare the resulting
      confidence intervals with the ones obtained through Basawa and Koul's minimum
      dispersion statistic. Furthermore, we obtain confidence intervals for the age and
      treatment effects in a lung cancer data set.

PMID- 19112528
TI  - Light-induced translocation of cyclic-GMP phosphodiesterase on rod disc membranes
      in rat retina.
AB  - PURPOSE: Cyclic GMP phosphodiesterase (PDE) is the light-regulated effector
      enzyme of vertebrate rods. Upon photo-activation of rhodopsin followed by
      activation of transducin/GTP, PDE rapidly hydrolyzes 3', 5'-cyclic GMP (cGMP) to
      5'-GMP, which results in closure of cGMP-dependent ion channels and generation of
      a nerve signal. In the rod photoreceptors, PDE is entirely localized within the
      rod outer segment (ROS), a specialized compartment consisting of thousands of
      disc stacks. This study investigated the effects of light on the subcellular
      localization of PDE in ROS. METHODS: Adult rats were either dark- or light
      adapted for various durations before eyes were isolated and processed for
      transmission electron microscopy. Immunogold electron microscopy was performed
      with antibodies against PDE. Lateral displacement of PDE on ROS disc membrane was
      analyzed from electron micrographs. PDE enzymatic activities were measured with
      thin layer chromatography. RESULTS: Light exposure induced translocation of PDE
      away from the edges of the dark-adapted disc membranes adjacent to the ROS plasma
      membrane. In dark-adapted ROS, a substantial portion (19+/-2%) of total PDE was
      localized near the edges of the disc membranes. Within 1 min of light exposure in
      the presence of GTP, over half of such PDE molecules (10+/-1% of total PDE) had
      moved away from the edges of the discs toward disc center. This light induced
      translocation of PDE was GTP dependent, as the effect was abolished when
      hydrolysis-resistant GTPgammaS was used in place of GTP. The percentage of PDE
      found near the disc edge corresponds to the fraction of PDE activity relative to
      maximal PDE activity revealed by limited trypsin proteolysis. CONCLUSIONS: These
      results suggest that light and GTP modulates lateral displacement of PDE, which
      might contribute to light-induced reduction of rod photoreceptor sensitivity.

PMID- 19112529
TI  - Topographical characterization of cone photoreceptors and the area centralis of
      the canine retina.
AB  - PURPOSE: The canine is an important large animal model of human retinal genetic
      disorders. Studies of ganglion cell distribution in the canine retina have
      identified a visual streak of high density superior to the optic disc with a
      temporal area of peak density known as the area centralis. The topography of cone
      photoreceptors in the canine retina has not been characterized in detail, and in
      contrast to the macula in humans, the position of the area centralis in dogs is
      not apparent on clinical funduscopic examination. The purpose of this study was
      to define the location of the area centralis in the dog and to characterize in
      detail the topography of rod and cone photoreceptors within the area centralis.
      This will facilitate the investigation and treatment of retinal disease in the
      canine. METHODS: We used peanut agglutinin, which labels cone matrix sheaths and
      antibodies against long/medium wavelength (L/M)- and short wavelength (S)-cone
      opsins, to stain retinal cryosections and flatmounts from beagle dogs. Retinas
      were imaged using differential interference contrast imaging, fluorescence, and
      confocal microscopy. Within the area centralis, rod and cone size and density
      were quantified, and the proportion of cones expressing each cone opsin subtype
      was calculated. Using a grid pattern of sampling in 9 retinal flatmounts, we
      investigated the distribution of cones throughout the retina to predict the
      location of the area centralis. RESULTS: We identified the area centralis as the
      site of maximal density of rod and cone photoreceptor cells, which have a smaller
      inner segment cross-sectional area in this region. L/M opsin was expressed by the
      majority of cones in the retina, both within the area centralis and in the
      peripheral retina. Using the mean of cone density distribution from 9 retinas, we
      calculated that the area centralis is likely to be centered at a point 1.5 mm
      temporal and 0.6 mm superior to the optic disc. For clinical funduscopic
      examination, this represents 1.2 disc diameters temporal and 0.4 disc diameters
      superior to the optic disc. CONCLUSIONS: We have described the distribution of
      rods and cone subtypes within the canine retina and calculated a predictable
      location for the area centralis. These findings will facilitate the
      characterization and treatment of cone photoreceptor dystrophies in the dog.

PMID- 19112530
TI  - Identification of two novel OPA1 mutations in Chinese families with autosomal
      dominant optic atrophy.
AB  - PURPOSE: To report the clinical features and identification of two novel
      mutations in two Chinese pedigrees with autosomal dominant optic atrophy (ADOA).
      METHODS: Two families (F1 and F2) including ten affected members and nine
      unaffected family individuals were examined clinically. After informed consent
      was obtained, peripheral blood samples of all the participants were obtained, and
      genomic DNA was extracted. Linkage analysis was performed with two microsatellite
      markers around the OPA1 gene (D3S2305 and D3S3562) in family F1. The coding
      region (exon 1-28), including intron-exon boundary of the OPA1 gene, were
      screened in the 2 families by polymerase chain reaction (PCR) and direct DNA
      sequencing. Whenever substitutions were identified in a patient, single strand
      conformation polymorphism (SSCP) analysis was performed on all available family
      members and 100 normal controls. To characterize a splicing site mutation, RT-PCR
      of total RNA of leukocytes obtained from three patients and seven unaffected
      individuals of family F1 was performed with the specific primers. RESULTS: The
      affected individuals all presented with bilateral visual failure and temporal or
      total pallor of the optic discs. Genotyping of family F1 revealed the linkage to
      the OPA1 gene on 3q28-29. After sequencing of OPA1 gene, a novel heterozygous
      splicing site mutation c.985 -2A>G in intron 9 was found in family F1. RT-PCR
      result showed the skipping of the exon 10 in the mutant transcript, which results
      in loss of 27 amino acids in the OPA1 protein. A novel heterozygous nonsense
      mutation c.2197C>T(p.R733X)was detected in family F2. CONCLUSIONS: Our findings
      expand the spectrum of OPA1 mutations and further established the role of OPA1
      gene in Chinese patients with ADOA.

PMID- 19112531
TI  - Identification of STRA6 and SKI sequence variants in patients with
      anophthalmia/microphthalmia.
AB  - PURPOSE: Anophthalmia and microphthalmia (A/M) are rare congenital ocular
      malformations presenting with the absence of eye components or small eyes with or
      without structural abnormalities. A/M can be isolated or syndromic. The
      stimulated by retinoic acid gene 6 (STRA6) and Sloan-Kettering viral oncogene
      homolog (SKI) genes are involved in vitamin A metabolism, and are implicated with
      A/M developmental abnormalities in human and animal studies. Vitamin A metabolism
      is vital to normal eye development and growth. This study explores the
      association of these genes in a cohort of subjects with A/M. METHODS: STRA6 and
      SKI were screened for sequence variants by direct sequencing of genomic DNA
      samples from 18 affected subjects with A/M. The DNA samples of 4 external,
      unrelated controls were initially screened. Eighty-nine additional unrelated
      controls were screened to confirm that any sequence variants found in the
      affected subject DNA samples were related to the phenotype. Coding regions,
      intron-exon boundaries, and untranslated regions were sequenced by standard
      techniques. Derived DNA sequences were compared to known reference sequences from
      public genomic databases. RESULTS: For STRA6, a novel coding non-synonymous
      sequence variant was found in one subject, resulting in an amino acid change from
      glycine to glutamic acid in residue 217. One novel nonsense sequence variant
      found in the same subject changed the STRA6 amino acid residue 592 from cytosine
      to thymine resulting in a premature stop codon. For SKI, a known coding non
      synonymous sequence variant (rs28384811) was found in 3 subject DNA samples and
      11/89 control DNA samples. Four novel coding-synonymous sequence variants were
      observed in SKI. CONCLUSIONS: The STRA6 sequence variants reported in this study
      could play a role in the pathogenesis of A/M by structural changes to the STRA6
      protein. We can attribute 4% A/M incidence in this cohort to these sequence
      variants. Although no SKI sequence variants were found in this cohort, SKI should
      not be ruled out as a candidate gene for A/M due to the small cohort size.

PMID- 19112532
TI  - The neurovascular relation in oxygen-induced retinopathy.
AB  - PURPOSE: Longitudinal studies in rat models of retinopathy of prematurity (ROP)
      have demonstrated that abnormalities of retinal vasculature and function change
      hand-in-hand. In the developing retina, vascular and neural structures are under
      cooperative molecular control. In this study of rats with oxygen-induced
      retinopathy (OIR) models of ROP, mRNA expression of vascular endothelial growth
      factor (VEGF), semaphorin (Sema), and their neuropilin receptor (NRP) were
      examined during the course of retinopathy to evaluate their roles in the observed
      neurovascular congruency. METHODS: Oxygen exposures designed to induce
      retinopathy were delivered to Sprague-Dawley rat pups (n=36) from postnatal day
      (P) 0 to P14 or from P7 to P14. Room-air-reared controls (n=18) were also
      studied. Sensitivities of the rod photoreceptors (S(rod)) and the postreceptor
      cells (Sm) were derived from electroretinographic (ERG) records. Arteriolar
      tortuosity, T(A), was derived from digital fundus images using Retinal Image
      multi-Scale Analysis (RISA) image analysis software. mRNA expression of
      VEGF(164), semaphorin IIIA (Sema3A), and neuropilin-1 (NRP-1) was evaluated by RT
      PCR of retinal extracts. Tests were performed at P15-P16, P18-P19, and P25-P26.
      Relations among ERG, RISA, and PCR parameters were evaluated using linear
      regression on log transformed data. RESULTS: Sm was low and T(A) was high at
      young ages, then both resolved by P25-P26. VEGF(164) and Sema3A mRNA expression
      were also elevated early and decreased with age. Low Sm was significantly
      associated with high VEGF(164) and Sema3A expression. Low S(rod) was also
      significantly associated with high VEGF(164). S(rod) and Sm were both correlated
      with T(A). NRP-1 expression was little affected by OIR. CONCLUSIONS: The
      postreceptor retina appears to mediate the vascular abnormalities that
      characterize OIR. Because of the relationships revealed by these data, early
      treatment that targets the neural retina may mitigate the effects of ROP.

PMID- 19112533
TI  - Targeting retinal dopaminergic neurons in tyrosine hydroxylase-driven green
      fluorescent protein transgenic zebrafish.
AB  - PURPOSE: Dopamine plays key roles in a variety of basic functions in the central
      nervous system. To study developmental and functional roles of dopaminergic cells
      in zebrafish, we have generated a transgenic line of zebrafish expressing green
      fluorescent protein (GFP) under the control of the tyrosine hydroxylase (th1)
      promoter. METHODS: A 12 kb gene fragment that contains the th1 promoter was
      isolated and ligated to the MmGFP coding sequence, linearized, microinjected into
      1-2 cell stage embryos and the founders crossed with wild-type fish to screen for
      transgenic lines. Tg(-12th:MmGFP) embryos were visualized under fluorescence
      microscopy for GFP expression during development. Confocal microscopy was used to
      visualize GFP-labeled cells in the living whole mount retina and immunostained
      vertical sections of adult zebrafish retina. Single-cell reverse transcription
      polymerase chain reaction (RT-PCR) was performed on individual GFP+ cells
      collected from dispersed retinal cell cultures for th1 and dopamine transporter
      (dat). Loose-patch recordings of spike activity of GFP+ neurons were made in
      isolated whole mount retinas. RESULTS: th1 promoter-driven GFP exhibited robust
      expression in the brain and retina during zebrafish development. In juvenile and
      adult fish retinas, GFP was expressed in cells located in the inner nuclear
      layer. Immunocytochemistry with antibodies for GFP and TH showed that 29+/-2% of
      GFP-labeled cells also expressed TH. Two subpopulations of GFP-labeled cells were
      identified by fluorescent microscopy: bright GFP-expressing cells and dim GFP
      expressing cells. Seminested single-cell RT-PCR showed that 71% of dim GFP
      expressing cells expressed both th and dat mRNA. Loose-patch voltage-clamp
      recording from dim GFP-labeled cells in retinal whole mounts revealed that many
      of these dopaminergic neurons are spontaneously active in darkness. CONCLUSIONS:
      Although this Tg(-12th:MmGFP) line is not a completely specific reporter for
      dopaminergic neurons, using relative GFP intensity we are able to enrich for the
      selection of retinal dopaminergic cells in vitro and in situ in molecular and
      electrophysiological experiments. This transgenic line provides a useful tool for
      studying retinal dopaminergic cells in the zebrafish.

PMID- 19112534
TI  - Lack of association of polymorphisms in homocysteine metabolism genes with
      pseudoexfoliation syndrome and glaucoma.
AB  - PURPOSE: To evaluate genes involved in homocysteine metabolism as secondary risk
      factors for pseudoexfoliation syndrome (PXFS) and the associated glaucoma (PXFG).
      METHODS: One hundred eighty-six unrelated patients with PXFS, including 140
      patients with PXFG and 127 unrelated control subjects were recruited from the
      Massachusetts Eye and Ear Infirmary. All the patients and controls were Caucasian
      of European ancestry. Seventeen tag SNPs from 5 genes (methylenetetrahydrofolate
      reductase [MTHFR], methionine synthase [MTR], methionine synthase reductase
      [MTRR], methylenetetrahydrofolate dehydrogenase [MTHFD1], and cystathionine beta
      synthase [CBS]) were genotyped. Single-SNP association was analyzed using
      Fisher's exact test (unconditional) or logistic regression after conditioning on
      the effects of age and three LOXL1 SNPs (rs1048661, rs3825942, and rs2165241).
      Interaction analysis was performed between the homocysteine and LOXL1 SNPs using
      logistic regression. Haplotype analysis and the set-based test were used to test
      for association of individual genes. Multiple comparisons were corrected using
      the Bonferroni method. RESULTS: One SNP (rs8006686) in MTHFD1 showed a nominally
      significant association with PXFG (p=0.015, OR=2.23). None of the seventeen SNPs
      tested were significantly associated with PXFS or PXFG after correcting for
      multiple comparisons (Bonferroni corrected p>0.25). After controlling for the
      effects of age and three associated LOXL1 SNPs, none of the seventeen tested SNPs
      were associated with PXFS (p>0.12). No significant interaction effects on PXFS
      were identified between the homocysteine and LOXL1 SNPs (p>0.06). Haplotype
      analysis and the set-based test did not find significant association of
      individual genes with PXFS (p>0.23 and 0.20, respectively). CONCLUSIONS: Five
      genes that are critical components of the homocysteine metabolism pathway were
      evaluated as secondary factors for PXFS and PXFG. Our results suggest that these
      genes are not significant risk factors for the development of these conditions.

PMID- 19112536
TI  - An unusual presentation: renal tuberculosis.
AB  - Genitourinary tuberculosis (TB) is the second most common form of extrapulmonary
      TB after peripheral lymphadenopathy. We report the case of a 44-year-old woman
      referred for hydronephrosis discovered on ultrasound performed due to flank pain.
      Contrast computed tomography (CT) scan demonstrated a well-circumscribed cystic
      mass with enhancing septations at the inferior pole of the right kidney,
      concerning for malignancy. Following extirpative surgery, she was diagnosed with
      renal TB.

PMID- 19112535
TI  - Human anterior chamber angle development without cell death or macrophage
      involvement.
AB  - PURPOSE: The iridocorneal angle in the mammalian eye including the trabecular
      meshwork (TM) develops from undifferentiated mesenchyme/neural crest between the
      iris root and cornea. The precise mechanisms underlying anterior angle
      development are unclear, and the contribution of cell death and phagocytic
      resorption by macrophages in angle development is controversial. In this study,
      we examined the human anterior chamber angle during various stages of development
      for evidence of cell death and phagocytic resorption. METHODS: Eyes from the
      human fetus (F) of 7, 8, 9, 10, 11, 13, 15, 18, 19, 21, 22, 23, and 27 weeks as
      well as eyes from 5- and 11-month-old children and donors 24, 48, and 67 years of
      age were obtained. Formalin-fixed and paraffin-embedded sections were examined by
      hematoxylin and eosin (H&E) staining. Immunohistochemistry was performed using
      polyclonal antibodies against CD68. Terminal deoxynucleotidyl transferase dUTP
      nick end labeling (TUNEL) labeling was also performed to evaluate cell death.
      RESULTS: By light microscopy, the development of human angle structures appeared
      to progress as previously described. Histological evidence of cellular death or
      resorption by macrophages was not observed. Furthermore, the chamber angle
      tissues did not stain with CD68 at any stage of development. Few CD68 positive
      cells were observed in the iris stroma and the anterior ciliary body between
      fetal weeks 10 and 18 (F10w and F18w). TUNEL labeled nuclei were not detected in
      the anterior chamber angle in any fetal or infant eyes. By contrast, TUNEL
      positive nuclei in TM cells were observed in the examined adult donor specimens.
      CONCLUSIONS: The results suggest that at the time points examined, neither cell
      death nor phagocytic resorption with macrophages appear to play a role in the
      development of the human anterior chamber angle.

PMID- 19112537
TI  - Paraganglioma of the spermatic cord: case report and review of the literature.
AB  - Paragangliomas rarely involve the genitourinary tract. We present a case of a
      paraganglioma arising from the spermatic cord and review the literature on the
      topic.

PMID- 19112538
TI  - Clarifying the role of urodynamics in the preoperative evaluation of stress
      urinary incontinence.
AB  - It has not yet been definitively demonstrated that preoperative evaluation of
      women with stress urinary incontinence (SUI) with urodynamic testing (UDS)
      enhances surgical outcomes. Nonetheless, UDS is frequently utilized in the
      assessment of women with SUI in the hopes that results will shed light on
      preoperative risk factors for failure or postoperative voiding dysfunction.
      Poorer outcomes for stress incontinence surgery are primarily attributed to
      intrinsic sphincter deficiency (ISD), detrusor overactivity (DO), and voiding
      dysfunction. The ability of UDS to identify and characterize those parameters
      reliably remains under investigation. Furthermore, debate continues regarding the
      association of each of those factors with postoperative success for various SUI
      procedures. Since UDS is invasive, costly, and not always available, it is
      imperative that its benefit be carefully explored. In this review, we discuss the
      value of UDS in identifying risk factors for poor outcome and how those risk
      factors are associated with surgical failure.

PMID- 19112539
TI  - Influence of poly(L-lactic acid) nanofibers and BMP-2-containing poly(L-lactic
      acid) nanofibers on growth and osteogenic differentiation of human mesenchymal
      stem cells.
AB  - The aim of this study was to characterize synthetic poly-(L-lactic acid) (PLLA)
      nanofibers concerning their ability to promote growth and osteogenic
      differentiation of stem cells in vitro, as well as to test their suitability as a
      carrier system for growth factors. Fiber matrices composed of PLLA or BMP-2
      incorporated PLLA were seeded with human mesenchymal stem cells and cultivated
      over a period of 22 days under growth and osteoinductive conditions, and analyzed
      during the course of culture, with respect to gene expression of alkaline
      phosphatase (ALP), osteocalcin (OC), and collagen I (COL-I). Furthermore, COL-I
      and OC deposition, as well as cell densities and proliferation, were analyzed
      using fluorescence microscopy. Although the presence of nanofibers diminished the
      dexamethasone-induced proliferation, there were no differences in cell densities
      or deposition of either COL-I or OC after 22 days of culture. The gene expression
      of ALP, OC, and COL-I decreased in the initial phase of cell cultivation on PLLA
      nanofibers as compared to cover slip control, but normalized during the course of
      cultivation. The initial down-regulation was not observed when BMP-2 was directly
      incorporated into PLLA nanofibers by electrospinning, indicating that growth
      factors like BMP-2 might survive the spinning process in a bioactive form.

PMID- 19112540
TI  - Electric fields and inflammation: may the force be with you.
AB  - Integrins are a family of ubiquitous cell surface receptors comprising
      heterodimers of alpha and beta chains that are required for cell adhesion and
      motility. Integrin-dependent adhesion and signaling is associated with major
      conformational changes in the ectodomain as it shifts from a low-affinity "bent"
      to a high-affinity "extended" structure. The ability of a cell to regulate
      dynamically the affinity or activation state of an integrin, and hence its
      binding to extracellular matrix or cell adhesion molecules, is assumed to be
      driven by intracellular signaling events transmitted by protein binding to the
      cytoplasmic tail. The binding of an integrin to its ligand can then transmit
      signals back into the cell to regulate the formation of a macromolecular focal
      adhesion complex that effectively anchors the cytoskeleton to the adhesion site.
      Many proteins have been reported to associate physically and functionally with
      integrins, leading to altered signaling events. A particularly intriguing
      molecular association exists between integrins and transmembrane proteins that
      gate the movement of charge, especially voltage-gated potassium channels,
      although the significance of this interaction is not understood. Although ample
      evidence indicates that the engagement of integrins can promote potassium efflux
      by both excitable and nonexcitable cells, we speculate the converse, that the
      activation state of integrins is dynamically regulated by changes in a
      transmembrane potential. In this way, direct-current electric fields generated at
      a site of tissue injury can promote the galvanotaxis or directed migration of
      cells involved in tissue repair and inflammation.

PMID- 19112541
TI  - Sickle cell anemia, the first molecular disease: overview of molecular etiology,
      pathophysiology, and therapeutic approaches.
AB  - The root cause of sickle cell disease is a single beta-globin gene mutation
      coding for the sickle beta-hemoglobin chain. Sickle hemoglobin tetramers
      polymerize when deoxygenated, damaging the sickle erythrocyte. A multifaceted
      pathophysiology, triggered by erythrocyte injury induced by the sickle hemoglobin
      polymer, and encompassing more general cellular and tissue damage caused by
      hypoxia, oxidant damage, inflammation, abnormal intracellular interactions, and
      reduced nitric oxide bioavailability, sets off the events recognized clinically
      as sickle cell disease. This disease is a group of related disorders where sickle
      hemoglobin is the principal hemoglobin species. All have varying degrees of
      chronic hemolytic anemia, vasculopathy, vasoocclusive disease, acute and chronic
      organ damage, and shortened life span. Its complex pathophysiology, of which we
      have a reasonable understanding, provides multiple loci for potential therapeutic
      intervention.

PMID- 19112542
TI  - Inhibition of steroid sulfatase activity in endometriotic implants by STX64
      (667Coumate): a potential new therapy.
AB  - Endometriosis is a common and debilitating condition of women in their
      reproductive age that is associated with pain and infertility. Current medical
      treatments are only partially effective and associated with wide-ranging side
      effects. New understanding of local estrogen production by endometriotic tissue
      and the availability of powerful suppressing drugs may herald a new era in the
      treatment of this condition.

PMID- 19112543
TI  - [Endoscopy-assisted surgery of the sellar region].
AB  - OBJECTIVE: To evaluate the usefulness of endoscopic assisted surgery of pituitary
      adenomas in transesphenoidal surgery, and in surgery of craneopharyngiomas using
      either minimally invasive approaches to the cranial base or transventricular
      approaches. MATERIAL AND METHODS: We present our preliminary experience in eleven
      patients operated of sellar region tumor by endoscopic assisted resection: 6
      pituitary adenoma via transesphenoidal approach, 4 craneopharyngiomas 3 through
      supraciliar approach and 1 by transcortical transventricular approach, and 1
      suprasellar cyst. RESULTS: By using the 30 degrees optic the use of endoscope
      allowed complete resection, confirmed by postoperative MRI, of all six pituitary
      macroadenomas providing control of resection of supraselar remnants. Complete
      resection was achieved in three out of four craneopharyngiomas, 2 of them being
      recurrences. Three were operated by using a supraciliar approach to the cranial
      base and in one case transcortical transventricular resection of a recurrent
      intraventricular craneopharyngioma was performed. In the case with partial
      resection remnant were let in place due to the close adherence to peritumoral
      structures. In the three craneopharyngiomas operated via supraciliar approach
      endoscope allowed better control of inferior aspect of ipsilateral optic nerve
      and internal carotid artery. In the case of intraventricular craneopharyngioma,
      the use of 30 degrees endoscope provide control of resection of the anterior part
      of third ventricle through the foramen of Monro with no additional opening. The
      suprasellar cyst was fenestrated. CONCLUSIONS: No matter which approach is going
      to be used in the resection of sellar tumors, endoscopy can play a crucial role
      in achieve complete resection with minimal morbidity by using minimally invasive
      procedures.

PMID- 19112544
TI  - Comments to Esparza et al's article "Surgical treatment of isolated and syndromic
      craniosynostosis. Results and complications in 283 consecutive cases".

PMID- 19112545
TI  - Surgical treatment of isolated and syndromic craniosynostosis. Results and
      complications in 283 consecutive cases.
AB  - OBJECTIVE: To review the results and complications of the surgical treatment of
      craniosynostosis in 283 consecutive patients treated between 1999 and 2007.
      PATIENTS AND METHODS: Our series consisted of 330 procedures performed in 283
      patients diagnosed with scaphocephaly (n=155), trigonocephaly (n=50), anterior
      plagiocephaly (n=28), occipital plagiocephaly (n=1), non-syndromic multi-suture
      synostosis (n=20), and with diverse craniofacial syndromes (n=32; 11 Crouzon, 11
      Apert, 7 Pfeiffer, 2 Saethre-Chotzen, and 2 clover-leaf skull). We used the
      classification of Whitaker et al. to evaluate the surgical results. Complications
      of each technique and time of patients' hospitalization were also recorded. The
      surgeries were classified in 12 different types according to the techniques used.
      Type I comprised endoscopic assisted osteotomies for sagittal synostosis (42
      cases). Type II included sagittal suturectomy and expanding osteotomies (46
      cases). Type III encompassed procedures similar to type II but that included
      frontal dismantling or frontal osteotomies in scaphocephaly (59 cases). Type IV
      referred to complete cranial vault remodelling (holocranial dismantling) in
      scaphocephaly (13 cases). Type V belonged to fronto-orbital remodelling without
      fronto-orbital bandeau in trigonocephaly (50 cases). Type VI included fronto
      orbital remodelling without fronto-orbital bandeau in plagiocephaly (14 cases).
      In Type VII cases of plagiocephaly with frontoorbital remodelling and fronto
      orbital bandeau were comprised (14 cases). Type VIII consisted of occipital
      advancement in posterior plagiocephaly (1 case). Type IX included standard
      bilateral fronto-orbital advancement with expanding osteotomies (30 cases). Type
      X was used in multi-suture craniosynostosis (15 cases) and consisted of
      holocranial dismantling (complete cranial vault remodelling). Type XI included
      occipital and suboccipital craniectomies in multiple suture craniosynostosis (10
      cases) and Type XII instances of fronto-orbital distraction (26 cases). RESULTS:
      The mortality rate of the series was 2 out of 283 cases (0.7%). These 2 patients
      died one year after surgery. All complications were resolved without permanent
      deficit. Mean age at surgery was 6.75 months. According to Whitaker et al's
      classification, 191 patients were classified into Category I (67.49%), 51 into
      Category II (18.02%), 30 into Category III (10.6%) and 14 into Category IV
      (4.90%). Regarding to craniofacial conformation, 85.5 % of patients were
      considered as a good result and 15.5% of patients as a poor result. Of the
      patients with poor results, 6.36% were craniofacial syndromes, 2.12% had anterior
      plagiocephaly and 1.76% belonged to non-syndromic craniosynostosis. The most
      frequent complication was postoperative hyperthermia of undetermined origin
      (13.43% of the cases), followed by infection (7.5%), subcutaneous haematoma
      (5.3%), dural tears (5%), and CSF leakage (2.5%). The number of complications was
      higher in the group of re-operated patients (12.8% of all). In this subset of
      reoperations, infection accounted for 62.5%, dural tears for 93% and CSF leaks
      for 75% of the total. In regard to the surgical procedures, endoscopic assisted
      osteotomies presented the lowest rate of complications, followed by standard
      fronto-orbital advancement in multiple synostosis, trigonocephaly and
      plagiocephaly. The highest number of complications occurred in complete cranial
      vault remodelling (holocranial dismantling) in scaphocephaly and multiple
      synostoses and after the use of internal osteogenic distractors. Of note, are two
      cases of iatrogenic basal encephalocele that occurred after combined fronto
      facial distraction. CONCLUSIONS: The best results were obtained in patients with
      isolated craniosynostosis and the worst in cases with syndromic and multi-suture
      craniosynostosis. The rate and severity of complications were related to the type
      of surgical procedure and was higher among patients undergoing re-operations. The
      mean time of hospitalization was also modified by these factors. Finally, we
      report our considerations for the management of craniosynostosis taking into
      account each specific technique and the age at surgery, complication rates and
      the results of the whole series.

PMID- 19112546
TI  - [Bidimensional-ultrasound guided-craniotomy in the excision of supratentorial
      brain tumours].
AB  - OBJECTIVES: With this 1-year retrospective study we aimed to analyze our
      experience on the utilization of real-time bidimensional (2-D) ultrasonography as
      an aid for the localization of deep-seated supratentorial brain tumours. MATERIAL
      AND METHODS: During the year 2006 we performed 2-D ultrasonographic localization
      studies in patients undergoing excision of subcortical supratentorial brain
      tumours whose nature was pathologically proven. The ultrasound machines utilized
      were 2410 A ultrasounds HP and Phillips HDI 3500 ATL. To check gross anatomical
      structures we used a 3 MHz probe and then a 5 MHz sound to define the brain
      tumour characteristics. Coronal and sagittal cuts were obtained during parietal
      or temporal craniotomies, and axial and sagittal slices in the case of frontal
      masses. After brain tumour removal and after a thorough irrigation with saline,
      new image acquisitions were performed to confirm the completeness of tumour
      excision. The amount of removed tumour was also verified by a post-contrast
      computerized tomography (CT) scan performed after the surgery. RESULTS: The study
      group was composed by 30 patients with ages comprised between 28 and 82 years.
      The time required for tumour localization was 17.5 (+/- 1.9) min. The lesions
      were approached though 8 temporal, 7 parieto-occipital, 8 parietal, 2 fronto
      parietal and 5 temporo-parietal craniotomies. Mean depth of the lesions was 5.3
      (+/- 1.6) cm. The histopathologic diagnosis was 17 high-grade gliomas, 3 low
      grade astrocytomas, 8 metastatic lesions and 2 oligo-astrocytomas. High-grade
      gliomas were more echogenic than low-grade tumours and than oedema. No residual
      tumour was detected at the end of the surgery except in two cases in which a
      tumoral rest was left due to the proximity of the lesion to eloquent cerebral
      areas. Postoperative CT scans confirmed the completeness of tumour removal in the
      patients of the study as assessed by intraoperative ultrasounds. CONCLUSIONS:
      Real-time 2-D ultrasonography affords an adequate image quality for performing
      guided-craniotomy in supratentorial brain tumours, as it allows for a safe and
      accurate localization of the lesions. Its use is mainly indicated in the removal
      of tumours located in, or close to, important anatomical and functional brain
      areas and to depict the presence of tumour rests after surgical removal of
      cerebral neoplasms.

PMID- 19112547
TI  - [Vertebral reinforcement by means of kyphoplasty in the treatment of non
      osteoporotic thoraco-lumbar fractures. Study of 40 cases and review of the
      literature].
AB  - OBJECT: We present a series of patients with acute thoraco-lumbar fractures in
      whom we performed balloon vertebroplasty (kyphoplasty), either alone
      (percutaneous) or combined to posterior transpedicular fusion (open kyphoplasty).
      We emphasize the possibility of extending the use of kyphoplasty to non
      osteoporotic vertebral fractures, and combining this method with traditional
      posterior fusion procedures. METHODS: Between 2003 and 2005, 138 patients
      suffering from thoraco-lumbar acute fractures, were treated in our Department. 87
      corresponded to one vertebral level fractures; 34 to two levels, and the
      remaining 17 patients had more than two vertebrae affected. 65 patients (47%)
      received conservative therapy (rest in bed, physiotherapy, and subsequent
      progressive mobilization with cast). The remaining ones (73 cases; 43%) were
      treated invasively, performing balloon vertebroplasty alone (n=25), or
      kyphoplasty associated to posterior fusion in 15 cases (11%). Different kinds of
      screw posterior fusions were performed in the remaining patients (n=33; 24%). The
      latter group was not included in the present study. In the conservatively treated
      group (CTG), seven patients (11%) had a bad outcome, showing a persistency of
      hyperintensity in MRI-T2 sequences of the vertebral body, suggesting local edema.
      Mean hospitalization rate was 29 days in CTG. None of the 40 patients treated
      with kyphoplasty alone or combined with fusion showed abnormalities in
      neurological examination. They were classified in two groups: "Group a":
      Kyphoplasty alone (n=25). Mean of sagittal index in this group was 11 degrees
      (range: 6 degrees -15 degrees). In 9 patients, vertebral body collapse exceeded
      25%. Mean hospitalization rate was 14 days. "Group b": Kyphoplasty and posterior
      fusion techniques (n=15): Mean sagittal index was 23 degrees (range: 13 degrees -
      40 degrees). All the patients presented with a vertebral body collapse superior
      to 25%. All of them had posterior body wall involvement. This group was treated
      by surgery (decompression and fusion) and open vertebral body kyphoplasty. Mean
      hospitalization rate was 35 days. Clinical results of these 40 patients were
      measured by means of work status, restriction of physical activities and
      analgesic drug intake. Except for four patients of "Group b", 36 returned to
      their work. In 11 cases a slight reduction of physical activity was registered.
      Average "Group a" follow-up was 47 months (range: 10-72 months). A mean kyphosis
      correction of 5,3 degrees (sagittal index) was reached in this group. Average
      "Group b" follow-up was 26 months (range: 9-54). Mean kyphosis correction was
      10,3 degrees . As for complications, we registered three balloon disruptions and
      five leakages into the disc. CONCLUSIONS: Kyphoplasty could constitute an
      alternative and/or complementary treatment of traditional spinal stabilization
      fusion procedures in non osteoporotic vertebral fractures. Therefore, it should
      be offered, when indicated, as a substantial possible part of the treatment, to
      the patients suffering from vertebral fractures. Additional advantages of
      combining kyphoplasty and posterior fusion are the possibility of reducing the
      number of fused levels (shorter instrumentations), and to perform a 360 degree
      stabilization-remodeling through a single posterior approach.

PMID- 19112548
TI  - [Brain-stem tumors in children].
AB  - We report a large series of brain-stem tumors seen during 18 years of at our
      hospital. We diagnosed and treated a total of 42 patients between 1988 and 2006;
      36 of them were operated with partial resection in most cases. Brain-stem tumors
      constitute a rare condition with very bad prognosis. A surgical complete
      resection of the mass is not possible in most cases, so the principal surgical
      objective is reduction and decompression. The best prognosis is seen in patients
      with low grade tumors with minimal neurologic deficit. Most of these tumors cause
      death in a short period, usually one year or less.

PMID- 19112549
TI  - ["Idiopathic" syringomyelia: report of a case].
AB  - Syringomyelia is the condition in which cavities fulfilled with CSF are found
      within spinal cord. Syringes are caused by obstructions of CSF pathways of
      different causes. If we can not find a cause responsible for the blockage, we
      call it "idiopathic" syringomyelia. Drainage procedures have been widely used but
      results, especially long-term results, are not favourable and complication rate
      is high. Some authors prefer to restore CSF circulation instead to drain the
      syrinx. Results of this treatment modality are better in literature than drainage
      procedures. Adequate radiological studies help to identify problem location and
      to plan the approach. A case of "idiopathic" syringomyelia is presented.
      Treatment consisted on arachnoid webs dissection and dural plastia. Clinical and
      radiological response was good. Literature concerned about this kind of
      syringomyelia and treatment modalities are reviewed.

PMID- 19112550
TI  - Extremely delayed renal cell carcinoma metastasis mimicking convexity meningioma.
AB  - Cerebral extra-axial metastasis mimicking meningioma which satisfy several
      criteria for a diagnosis of meningioma, but which have proved instead to be
      metastatic carcinoma and extremely delayed cerebral metastasis from renal cell
      carcinoma, form the focus of the presentation. 68-year-old-woman who had been
      operated for renal cell carcinoma 20 years previously is presented with new
      symptoms of intracranial mass. A large extra-axial mass of the convexity which
      destroyed calvarium and dura was excised with Simpson Grade I removal, revealed
      metastatic carcinoma. Imaging characteristics can not always discern between
      meningioma and metastatic tumours. A meticulous clinical evaluation and
      histopathological diagnosis is essential in patients with intracranial mass even
      when they resemble both primary and metastatic tumours.

PMID- 19112552
TI  - Identification and characterization of a new coleviroid (CbVd-5).
AB  - A viroid-like RNA was detected from coleus (Coleus blumei) in China. It consisted
      of 274 nucleotides and had 66% sequence identity with a member of the closest
      known viroid species. The predicted secondary structure is rod-shaped with
      extensive base pairing, and it has the conserved region characteristic of the
      genus Coleviroid. Two terminal sequences that are highly conserved among some
      members of the genus were also identified. The viroid-like RNA was successfully
      transmitted to coleus by slash-inoculation. This viroid was identified as a new
      member of the genus Coleviroid, and we tentatively propose the name Coleus blumei
      viroid 5 (CbVd-5).

PMID- 19112551
TI  - Attenuation of skeletal muscle atrophy in cancer cachexia by D-myo-inositol 1,2,6
      triphosphate.
AB  - PURPOSE: To determine the effectiveness of the polyanionic, metal binding agent D
      myo-inositol-1,2,6-triphosphate (alpha trinositol, AT), and its hexanoyl ester
      (HAT), in tissue wasting in cancer cachexia. METHODS: The anti-cachexic effect
      was evaluated in the MAC16 tumour model. RESULTS: Both AT and HAT attenuated the
      loss of body weight through an increase in the nonfat carcass mass due to an
      increase in protein synthesis and a decrease in protein degradation in skeletal
      muscle. The decrease in protein degradation was associated with a decrease in
      activity of the ubiquitin-proteasome proteolytic pathway and caspase-3 and -8.
      Protein synthesis was increased due to attenuation of the elevated
      autophosphorylation of double-stranded RNA-dependent protein kinase, and of
      eukaryotic initiation factor 2alpha together with hyperphosphorylation of eIF4E
      binding protein 1 and decreased phosphorylation of eukaryotic elongation factor
      2. In vitro, AT completely attenuated the protein degradation in murine myotubes
      induced by both proteolysis-inducing factor and angiotensin II. CONCLUSION: These
      results show that AT is a novel therapeutic agent with the potential to alleviate
      muscle wasting in cancer patients.

PMID- 19112553
TI  - Different strategies for color change.

PMID- 19112555
TI  - Expressional profiling study revealed unique expressional patterns and dramatic
      expressional divergence of maize alpha-zein super gene family.
AB  - The alpha-zein super gene family encodes the most predominant storage protein in
      maize (Zea mays) endosperm. In maize inbred line B73, it consists of four gene
      families with 41 member genes. In this study, we combined quantitative real-time
      PCR and random clone sequencing to successfully profile the expression of alpha
      zein super gene family during endosperm development. We found that only 18 of the
      41 member genes were expressed, and their expression levels diverge greatly. At
      the gene family level, all families had characteristic "up-and-down" oscillating
      expressional patterns that diverged into two major groups. At the individual gene
      level, member genes showed dramatic divergence of expression patterns, indicating
      fast differentiation of their expression regulation. A comparison study among
      different inbred lines revealed significantly different expressed gene sets,
      indicating the existence of highly diverged haplotypes. Large gene families
      containing long gene clusters, e.g. z1A or z1C, mainly contributed the highly
      divergent haplotypes. In addition, allelic genes also showed significant
      divergence in their expressional levels. These results indicated a highly dynamic
      and fast evolving nature to the maize alpha-zein super gene family, which might
      be a common feature for other large gene families.

PMID- 19112554
TI  - Targeted transgene integration in plant cells using designed zinc finger
      nucleases.
AB  - Targeted transgene integration in plants remains a significant technical
      challenge for both basic and applied research. Here it is reported that designed
      zinc finger nucleases (ZFNs) can drive site-directed DNA integration into
      transgenic and native gene loci. A dimer of designed 4-finger ZFNs enabled intra
      chromosomal reconstitution of a disabled gfp reporter gene and site-specific
      transgene integration into chromosomal reporter loci following co-transformation
      of tobacco cell cultures with a donor construct comprised of sequences necessary
      to complement a non-functional pat herbicide resistance gene. In addition, a
      yeast-based assay was used to identify ZFNs capable of cleaving a native
      endochitinase gene. Agrobacterium delivery of a Ti plasmid harboring both the
      ZFNs and a donor DNA construct comprising a pat herbicide resistance gene
      cassette flanked by short stretches of homology to the endochitinase locus
      yielded up to 10% targeted, homology-directed transgene integration precisely
      into the ZFN cleavage site. Given that ZFNs can be designed to recognize a wide
      range of target sequences, these data point toward a novel approach for targeted
      gene addition, replacement and trait stacking in plants.

PMID- 19112556
TI  - Genomic organization of repetitive DNAs in the cichlid fish Astronotus ocellatus.
AB  - To contribute to the knowledge of fish genomes, we identified and characterized
      by means of nucleotide sequencing and physical chromosome mapping, three classes
      of repetitive DNAs in the genome of the South American cichlid fish Astronotus
      ocellatus. The first class corresponds to a satellite DNA family (AoSat) that
      shares similarity with a centromeric satellite DNA of the pufferfish Tetraodon
      nigroviridis. The second repetitive DNA class (AoRex3) is related to the
      retrotransposon Rex3, which is widely distributed among teleost fishes. The last
      repetitive element (AoLINE) shows a high similarity to the CR1-like LINE element
      of other teleosts. The three isolated repetitive elements are clustered in the
      centromeric heterochromatin of all chromosomes of the complement. The repetitive
      sequences are not randomly distributed in the genome, suggesting a pattern of
      compartmentalization on chromosomes.

PMID- 19112557
TI  - High Ag-NOR-site variation associated to a secondary contact in brown trout from
      the Iberian Peninsula.
AB  - The analysis of nucleolar organizer regions (NORs) using silver (Ag-) staining
      and in situ hybridization (ISH) in brown trout (Salmo trutta) from various river
      basins in the Iberian Peninsula revealed high variation in the number and
      location of NORs. A total of 17 different Ag-NOR sites were revealed in 10
      different chromosome pairs. Three different Ag-NOR patterns clustered by river
      basins and strongly associated to the internal transcribed spacer 1 (ITS1)
      variation were detected. The main variability in NOR-sites was found in a
      secondary contact between two divergent lineages of brown trouts at Duero basin.
      Our results confirmed the abrupt break in the spatial distribution of genetic
      variation of brown trout populations previously reported at Duero basin. We
      hypothesize that NOR-site variation might be a consequence of hybridization
      between divergent lineages of brown trouts and that NORs could play a major role
      in the maintenance of a hybrid zone in Duero basin via post-zygotic isolation
      mechanisms.

PMID- 19112559
TI  - Environmental contaminants in white-winged doves (Zenaida asiatica asiatica) from
      the Lower Rio Grande Valley of Texas, USA.
AB  - Our study determined if white-winged doves (WWDs; Zenaida asiatica asiatica)
      breeding in locations where environmentally persistent contaminants occur in the
      Lower Rio Grande Valley of Texas have levels of contaminants that can hinder
      reproduction. During summer 2003, 70 (32 males, 38 females) adult WWDs were
      collected from 8 at-risk sites. Liver tissues were analyzed for ten major and
      trace elements and muscle tissues were analyzed for 20 organochlorine compounds,
      21 polychlorinated biphenyl congeners, and toxaphene. Samples were compared to
      ten (five male, five female) captive-raised control WWDs. Arsenic, chromium, and
      lead were not detected or were below the detection limit, whereas copper, zinc,
      selenium, mercury, nickel, cadmium, and silver were detected in 70 (100%), 70
      (100%), 52 (74%), 21 (30%), 4 (6%), 1 (1%), and 1 (1%) WWDs, respectively. None
      of the detected elements had significant sampling site, bird gender, or Site x
      Gender interactions, and each occurred at background levels. Toxaphene and
      polychlorinated biphenyls were not detected, whereas DDE, dieldrin, gamma-BHC,
      and chlordane were detected in 13 (19%), 5 (7%), 2 (3%), and 1 (1%) field
      collected WWDs, respectively, but all concentrations occurred at background
      levels. Concentrations of elements and compounds in field-collected WWDs did not
      significantly differ from those of the controls. Correlations between leukocyte
      counts and detectable contaminants generally indicated no correlation between
      each percentage of leukocyte type present and levels of selenium, copper, zinc,
      mercury, or DDE detected. One sample that had 0.072 mug/g dieldrin exhibited a
      low lymphocyte percentage (66%) out of only five samples. Comparisons could not
      be made with gamma-BHC, chlordane, or the other elements that had a low number of
      samples with detectable levels. Overall, concentrations of elements and
      organochlorines found in WWDs were below levels known to impair reproduction and
      survival in birds.

PMID- 19112558
TI  - Differential activation of mitogen-activated protein kinases following high and
      low LET radiation in murine macrophage cell line.
AB  - Mitogen-activated protein kinases have been shown to respond to various stimuli
      including cytokines, mitogens and gamma irradiation, leading to cell
      proliferation, differentiation, or death. The duration of their activation
      determines the specificity of response to each stimulus in various cells. In this
      study, the crucial intracellular kinases, ERK, JNK, and p38 kinase involved in
      cell survival, death, or damage and repair were examined for their activity in
      RAW 264.7 cells at various time points after irradiation with 2 Gy doses of
      proton ions or X-rays. This is the first report that shows that the MAPK
      signaling induced after heavy ion or X-ray exposure is not the same. Unlike gamma
      irradiation, there was prolonged but marginal activation of prosurvival ERK
      pathway and significant activation of proapoptotic p38 pathway in response to
      high LET radiation.

PMID- 19112560
TI  - Characterization of cadmium uptake and translocation in a cadmium-sensitive
      mutant of rice (Oryza sativa L. ssp. japonica).
AB  - To understand the physiological mechanism that confers Cd sensitivity/tolerance,
      Cd uptake and translocation by Cd-sensitive mutant and wild-type rice seedlings
      were characterized using radioactive tracer. Time-dependent Cd accumulation
      during 210 min was 1.8-fold higher in roots of the mutant than of wild-type rice.
      The kinetics of Cd uptake showed that two processes were involved: a first, fast,
      probably passive process and a second, slower, possibly physiological process.
      After 96 h, more Cd was translocated to the shoot of mutant compared with wild
      type rice. Low temperature (2 degrees C), carbonyl cyanide m
      chlorophenylhydrazone, and dicyclohexylcarbodiimide inhibited Cd accumulation to
      a greater extent in mutant than wild-type rice, suggesting that metabolism plays
      a more important role in Cd uptake for the rice mutant. Cd uptake into the
      symplasm is linked to Ca2+ transport, as revealed by the inhibition of Cd
      accumulation by La and high Ca by equal percentages in both mutant and wild-type
      rice. Cd uptake and root-to-shoot translocation in the mutant were inhibited more
      markedly by Zn and Mn than in wild-type rice. This indicates that transport sites
      other than entry into the root symplasm are also stimulated in the mutant. The
      results suggest that enhanced absorption into the root and further accumulation
      in the shoot is one of the mechanisms involved in Cd accumulation and
      sensitivity, and the difference in Cd uptake and root-to-shoot translocation
      between mutant and wild-type rice may be mediated partly by energy supply and
      transporters for Zn and Mn.

PMID- 19112561
TI  - Carryover of perfluorooctanoic acid (PFOA) and perfluorooctane sulfonate (PFOS)
      from soil to plants.
AB  - Within the scope of a joint project to study soil-to-plant carryover of
      polyfluorinated compounds (PFCs), five cultivated plants (spring wheat, oats,
      potatoes, maize, and perennial ryegrass) were sown or planted in Mitscherlich
      pots. Six variants per species were used, each with a different concentration
      level of PFOA and PFOS (from 0.25 to 50 mg/kg as aqueous solution) to detect
      possible concentration dependence in the transfer of these two PFCs from soil to
      plant. PFOA and PFOS were detected by liquid chromatography-tandem mass
      spectrometry after appropriate sample preparation (partial drying, mincing,
      homogenizing, extraction). Since PFOA and PFOS presently represent the most
      widely studied PFCs, they are classified as "leading compounds." The results show
      that concentrations of PFOA/PFOS in the plants vary greatly, depending on the
      concentrations applied to the soil. PFOA values were higher than PFOS values in
      all plants except potatoes, in which these differences could be quite
      substantial. From the results presented here it can be seen that uptake and
      storage are much more intensive in the vegetative portion of the plant than
      relocation in the storage organs. This is particularly evident from the the
      comparison of concentrations found in the grain and ear and those in the straw or
      rest of the plant in spring wheat, oats, and maize. Transfer from "soil to crops"
      provides a possible explanation for the presence of PFCs in foodstuffs and in
      human body fluids such as blood, plasma, serum, or breast milk. The aim of the
      present study was to determine whether a statistically significant, concentration
      dependent carryover of PFOA and PFOS in crop plants can take place, which would
      provide a potential entrance point for these substances into the food chain.

PMID- 19112562
TI  - Occupational exposure to pesticides: blood cholinesterase activity in a farming
      community in Ghana.
AB  - A survey was undertaken to establish the extent of pesticide exposure in a
      farming community. Cholinesterase (ChE) activity in whole blood was used as a
      marker for assessing exposure to pesticides. Complete data were gathered for 63
      farmers at Akumadan (exposed) and 58 control subjects at Tono, both prominent
      vegetable-farming communities in Ghana, by means of a questionnaire and blood
      cholinesterase analyses (acetylcholine assay). Although whole-blood ChE was
      significantly lower in the exposed than the control participants, it was not
      significantly correlated with either confounders of age, sex, body weight, and
      height or high-risks practices. The high-risks practices revealed during the
      survey included lack of use of personal protective clothing, short reentry
      intervals, and wrong direction of spraying of pesticides by hand or knapsack
      sprayer. About 97% of exposed participants had experienced symptoms attributable
      to pesticide exposure. The frequent symptoms were reported as weakness and
      headache. There is the need to review safety precautions in the use and
      application of pesticides in Ghana.

PMID- 19112563
TI  - The horsetail Equisetum arvense mitochondria share two group I introns with the
      liverwort Marchantia, acquired a novel group II intron but lost intron-encoded
      ORFs.
AB  - We studied the genomic structure and RNA editing of mitochondrial cox1, cox2, cob
      and atp9 from the horsetail Equisetum arvense, a representative of an old fern
      lineage. Editing of cox1, cob and atp9 mRNAs occur only by C-to-U transitions. No
      changes were found in cox2 transcripts constituting one of the rare examples of
      unedited mitochondrial mRNA in land plants. From three intervening sequences in
      cox1, cox1i395 and cox1i624 are group IB introns homologous to the Marchantia
      polymorpha cox1 introns, and cox1i747 is a group IIA intron different to other
      introns found in plant mtDNA. The group II intron cox2i373 is very similar to
      other introns found in cox2 from vascular plants. While cob and atp9 have no
      introns and display the gene structure found in seed plants, various nucleotide
      substitutions abolish the only potential ORF, a LAGLIDADG endonuclease present in
      cox1i395. Thus, E. arvense mitochondria conserve two group I introns from non
      vascular plants, probably inherited from a common ancestor with liverworts.
      Analogous to seed plants, E. arvense has no potential mitochondrial splicing
      factors encoded in these introns. This is the first report concerning the
      presence of vertically inherited group I introns in vascular plant mitochondria.

PMID- 19112564
TI  - Depression and its correlation with in patients pain in the rheumatology service
      of a Mexican teaching hospital.
AB  - The depressive symptoms are associated with chronic pain in this study. A cross
      sectional study was performed. A visual analog scale was used to register pain
      intensity. Depressive symptoms were measured using the Center of Epidemiological
      Studies (CES-Dr) scale as modified by Eaton and reviewed for use in the Mexican
      population. The study included 245 patients, with a mean age of 46 years, 86.1%
      of whom were female. The prevalence of some degree of depression was 55.1%.
      Patients with fibromyalgia had the highest prevalence of symptoms of depression
      (78.38%) and major depression (29.73%). Stepwise multiple regressions indicated
      that the best model (r2 = 0.26) to predict the CES-Dr score included the global
      pain score (P < 0.0001) and education level (P < 0.004). The Cronbach's alpha of
      the CES-Dr was high (alpha = 0.888). There was moderate correlation (r = 0.442),
      P < 0.0001 of the CES-Dr numeric score with the intensity of global pain.

PMID- 19112565
TI  - Regional diastolic function by tissue Doppler echocardiography in systemic
      sclerosis: correlation with clinical variables.
AB  - The incidence of left ventricular (LV) diastolic dysfunction is increased in
      systemic sclerosis (SSc), while systolic dysfunction is present in a small
      percentage of patients. The aim of this study was to asses the LV "regional"
      diastolic abnormalities in SSc patients by the mean of Doppler tissue imaging
      (DTI). Echocardiographic echo-Doppler (DE) and DTI parameters were analyzed for
      67 SSc patients: abnormal E/A ratio at DE was detected in 24, while abnormal e/a
      at DTI was observed in 41. A significant prevalence of DTI diastolic
      abnormalities in the segments reflecting longitudinal versus those reflecting
      radial LV motion was found. The segments of the basal regions of LV myocardium
      were significantly more involved than those of the middle portion. Linear
      correlation was observed between the extent of the diastolic abnormalities and
      the duration of disease. Longitudinal myocardial systolic velocities were
      significantly reduced in patients with abnormal e/a DTI.

PMID- 19112566
TI  - HvPG1 and ECA1: two genes activated transcriptionally in the transition of barley
      microspores from the gametophytic to the embryogenic pathway.
AB  - Microspores genetically programmed to produce male gametes can be switched to the
      embryogenic pathway to give rise to haploid embryos. Microspore embryogenesis is
      usually induced in barley by stress pre-treatment applied to vacuolated
      microspores. We studied the expression of two genes during the early stages of
      microspore embryogenesis to gain further insight into the microspore transition
      from the gametophytic to the embryogenic pathway. RT-PCR together with in situ
      hybridization on sections (ISH) and whole-mount in situ hybridization (WISH) were
      used to analyse the expression of the early-culture abundant gene (ECA1), which
      is expressed in barley during microspore embryogenesis, and a polygalacturonase
      gene (HvPG1), a late pollen gene expressed during gametogenesis only after
      microspore division. Both ECA1 and HvPG1 genes were transcriptionally active
      after stress pre-treatment in the same populations of microspore-derived
      structures, representing the sporophytically induced ones. ECA1 transcripts were
      also detected after 3 days' culture. Our results point to the possibility of
      using ECA1 gene expression as a marker for the induction of microspore
      embryogenesis and the earliest stages of this process. Finally, we demonstrate
      that WISH is a suitable technique for studying gene expression in embryogenic
      microspore populations and, because different structures can be examined
      individually, is an appropriate complement to transcriptomic profile analyses in
      the study of early microspore embryogenesis.

PMID- 19112567
TI  - Comparative sequence analysis for Brassica oleracea with similar sequences in B.
      rapa and Arabidopsis thaliana.
AB  - We sequenced five BAC clones of Brassica oleracea doubled haploid 'Early Big'
      broccoli containing major genes in the aliphatic glucosinolate pathway, and
      comparatively analyzed them with similar sequences in A. thaliana and B. rapa.
      Additionally, we included in the analysis published sequences from three other B.
      oleracea BAC clones and a contig of this species corresponding to segments in A.
      thaliana chromosomes IV and V. A total of 2,946 kb of B. oleracea, 1,069 kb of B.
      rapa sequence and 2,607 kb of A. thaliana sequence were compared and analyzed. We
      found conserved collinearity for gene order and content restricted to specific
      chromosomal segments, but breaks in collinearity were frequent resulting in gene
      absence likely not due to gene loss but rearrangements. B. oleracea has the
      lowest gene density of the three species, followed by B. rapa. The genome
      expansion of the Brassica species, B. oleracea in particular, is due to larger
      introns and gene spacers resulting from frequent insertion of DNA transposons and
      retrotransposons. These findings are discussed in relation to the possible origin
      and evolution of the Brassica genomes.

PMID- 19112568
TI  - Hibernation by a free-ranging subtropical bat (Nyctophilus bifax).
AB  - Knowledge about torpor in free-ranging subtropical bats is scarce and it is
      widely believed that low and stable ambient temperatures are necessary for
      prolonged torpor. We present temperature-telemetry data from free-ranging male (n
      = 4) and female (n = 4) subtropical vespertilionid bats, Nyctophilus bifax
      (approximately 10 g), exposed to pronounced daily fluctuations of ambient
      temperature. All bats used torpor on every day in winter and both males and
      females exhibited multi-day torpor bouts of up to 5.4 days. Although females were
      larger than males, patterns of torpor were similar in both sexes. Torpor use was
      correlated with prevailing weather conditions and, on days when bats remained
      torpid, maximum ambient temperature was significantly lower than on days when
      bats aroused. Moreover, the duration of interbout normothermic periods at night
      increased with increasing average nightly ambient temperature. Skin temperature
      of torpid bats varied by 10.2 +/- 3.6 degrees C day(-1) (n = 8, N = 47) and daily
      minimum skin temperature was positively correlated with the daily minimum ambient
      temperature. Our study shows that prolonged torpor is an important component of
      the winter ecology of a subtropical bat and that torpor and activity patterns of
      N. bifax predominantly reflect prevailing weather conditions.

PMID- 19112569
TI  - Claudin-8 and -27 tight junction proteins in puffer fish Tetraodon nigroviridis
      acclimated to freshwater and seawater.
AB  - Genes encoding for claudin-8 and -27 tight junction proteins in the euryhaline
      puffer fish (Tetraodon nigroviridis) were identified using its recently sequenced
      genome. Phylogenetic analysis indicated that multiple genes encoding for claudin
      8 proteins (designated Tncldn8a, Tncldn8b, Tncldn8c and Tncldn8d) arose by tandem
      gene duplication. In contrast, both tandem and whole genome duplication events
      appear to have generated genes encoding for claudin-27 proteins (designated
      Tncldn27a, Tncldn27b, Tncldn27c and Tncldn27d). Tncldn8 and Tncldn27 mRNA were
      widely distributed in Tetraodon, suggesting involvement in various physiological
      processes. All Tncldn8 and Tncldn27 genes were expressed in gill and skin tissue
      (i.e., epithelia exposed directly to the external environment). A potential role
      for claudin-8 and -27 proteins in the regulation of hydromineral balance in
      Tetraodon was investigated by examining alterations in mRNA abundance in select
      ionoregulatory tissue of fish acclimated to freshwater (FW) and seawater (SW). In
      FW or SW, Tetraodon exhibited alterations in Na(+)-K(+)-ATPase activity (a
      correlate of transcellular transport) typical of a euryhaline teleost fish.
      Simultaneously, tissue and gene specific alterations in Tncldn8 and Tncldn27
      transcript abundance occurred. These data provide some insight into the
      duplication history of cldn8 and cldn27 genes in fishes and suggest a possible
      role for claudin-8 and -27 proteins in the osmoregulatory strategies of
      euryhaline teleosts.

PMID- 19112570
TI  - Effects of phorbol 12-myristate 13-acetate on potassium transport in the red
      blood cells of frog Rana temporaria.
AB  - Phorbol 12-myristate 13-acetate (PMA), a stimulator of PKC, was examined for its
      influence on K(+) ((86)Rb) influx in the frog erythrocyte. PMA, 0.1 microM, was
      found to accelerate ouabain-sensitive K(+) influx, which was suppressed by 73%
      with 1 mM amiloride, indicating secondary activation of the Na(+)-K(+)-pump due
      to stimulation of Na(+ )/H(+) exchange. PMA-induced stimulation of the sodium
      pump was completely inhibited with 1 microM staurosporine and by approximately
      50% with 20 microM chelerythrine. In contrast to Na(+)-K(+)-pump, an activity of
      Cl(-)-dependent K(+) transport (K-Cl cotransport, KCC), calculated as the
      difference between K(+) influxes in Cl(-) and NO(3) (-)-media, was substantially
      decreased under the influence of PMA. Staurosporine fully restored the PMA
      induced inhibition of KCC, whereas chelerythrine did not exert any influence.
      Osmotic swelling of the frog erythrocytes was accompanied by approximately
      twofold stimulation of KCC. Swelling-activated KCC was inhibited by approximately
      50 and approximately 83% in the presence of PMA and genistein, respectively, but
      not chelerythrine. Exposure of the frog erythrocytes to 5 mM fluoride (F(-)) also
      reduced the KCC activity in isotonic and hypotonic media, with maximal
      suppression of K(+) influx in both media being observed upon simultaneous
      addition of PMA and F(-). Furosemide and [(dihydronindenyl)oxy] alkanoic acid
      inhibited the K(+) influx in both the media by approximately 50-60%. The results
      obtained show both the direct and indirect effects of PMA on the K(+) transport
      in frog erythrocytes and a complicated picture of KCC regulation in frog
      erythrocytes with involvement of PKC, tyrosine kinase and protein phosphatase.

PMID- 19112571
TI  - A functional single-nucleotide polymorphism in the catechol-O-methyltransferase
      gene alter vitiligo risk in a Chinese population.
AB  - Vitiligo is an acquired hypomelanotic skin disorder resulting from the loss of
      functional melanocytes. The COMT-158 polymorphism can reduce COMT enzyme activity
      and may thus lead to the overproduction of toxic radicals in the melanocyte
      microenvironment. To determine whether this polymorphism in the COMT gene is
      associated with an increased risk of vitiligo in Chinese populations, we used a
      polymerase chain reaction sequence-specific primer (PCR-SSP) technique to
      determine the frequency of the polymorphism COMT-158 G > A in 749 vitiligo
      patients and 763 healthy controls. We found that compared to the COMT-158 GG
      genotype, the COMT-158 GA genotype (adjusted odds ratio [OR], 1.39; 95%
      confidence interval [CI], 1.13-1.72) and the combined GA + AA genotype (adjusted
      OR, 1.41; 95% CI, 1.15-1.74) were associated with an increased risk of
      generalized vitiligo. The association was more pronounced in patients with early
      onset vitiligo (adjusted OR, 1.95; 95% CI, 1.45-2.60), those with a family
      history of vitiligo (adjusted OR, 3.84; 95% CI, 2.47-5.96), and female patients
      (adjusted OR, 1.74; 95% CI, 1.29-2.36). When we further clinically stratified the
      vitiligo patients according to their disease types, we found that the combined GA
      + AA genotype was associated with vitiligo vulgaris (adjusted OR, 1.31; 95% CI,
      1.02-1.68), focal vitiligo (adjusted OR, 1.62; 95% CI, 1.17-2.25), and universal
      vitiligo (adjusted OR, 1.50; 95% CI, 0.98-2.30), but not with acrofacial vitiligo
      (adjusted OR, 1.53; 95% CI, 0.86-2.73) or segmental vitiligo (adjusted OR, 1.35;
      95% CI, 0.72-2.51). In conclusion, this COMT gene polymorphism may have
      contributed to the etiology of vitiligo in our Chinese population. Larger
      population-based studies are required to verify our findings.

PMID- 19112572
TI  - Apoptosis patterns in eutopic and ectopic endometrium, adhesions and normal
      looking peritoneum from women with or without endometriosis.
AB  - OBJECTIVE: To assess the apoptosis rate in eutopic and ectopic endometrial
      stromal and glandular cells, normal peritoneum and adhesions in women with
      endometriosis. METHODS: A total number of 97 women with (n:60) and without (n:37)
      histopathologically confirmed endometriosis who underwent laparoscopy or
      laparotomy in the early follicular phase of the menstrual cycles for pain and
      infertility were included in this study. Stage I/II and stage III/IV were
      categorized as early staged and late-staged endometriosis. The endometrial
      samples were obtained with a Novack cannula from the corpus of the uterus. Normal
      looking peritoneum, peritoneal implants and adhesions were sampled and fixed in
      formaldehyde for immunohistochemical staining with Bcl-2 and Bax. Tissue samples
      were fixed in formaldehyde for the assessment of apoptosis via terminal
      deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick end labeling
      (TUNEL) and M30 cytoDEATH antibody. RESULTS: The intensity of Bax staining of
      normal-looking peritoneum in early staged endometriosis was higher, compared to
      women with late-staged and women without endometriosis (P = 0.03). However,
      degree of Bcl-2 staining did not differ among early and late-staged endometriosis
      and women without endometriosis (P = 0.1). In terms of Bcl-2 and Bax staining in
      the stromal and glandular parts of the eutopic endometria, no significant
      differences were detected among three groups. In cases with early- and late
      staged endometriosis the intensity of Bax and Bcl-2 stainings did not differ in
      both stromal and glandular parts of ectopic endometria. Number of cells with
      positive apoptotic signals assessed via TUNEL (P = 1.0) and M30 cytoDEATH
      antibody (P = 0.59) in normal-looking peritoneum did not differ between three
      groups. In addition, no difference in term of numbers of apoptotic cells obtained
      from adhesions was observed between three groups (for TUNEL, P = 0.29, for M30, P
      = 0.19). CONCLUSIONS: Apoptosis patterns did not differ in the eutopic and
      ectopic endometria as well as adhesions of women with or without endometriosis.

PMID- 19112573
TI  - Amniocentesis in twin pregnancies.
AB  - OBJECTIVE: To describe the experiences in diagnostic amniocentesis in twin
      pregnancies. METHODS: The computerized database and medical records of pregnant
      women attending Maternal Fetal Medicine Unit of the hospital for diagnostic
      amniocentesis at 16-20 weeks gestation between January 1992 and December 2006
      were retrospectively reviewed. RESULTS: During 15 years of experience, 7,890
      amniocenteses at 16-20 weeks gestation were performed for prenatal diagnosis,
      including 174 procedures in 87 twin pregnancies. The mean gestational age at the
      time of amniocentesis was 17.13 +/- 3.35 weeks. Preterm birth rate defined as the
      delivery before 36 gestational weeks was 36.24%. The total fetal loss rate was
      5.17%, however, the procedure related fetal loss within 2 weeks after the
      procedure was 1.15%. CONCLUSION: Based on our limited data and previous studies,
      we can counsel patients undergoing twin amniocentesis at mid-trimester that the
      fetal loss rate may be slightly higher than that of singleton amniocentesis.

PMID- 19112574
TI  - Do routine preoperative imaging techniques facilitate the operation in
      endometrial cancer?
AB  - OBJECTIVE: To assess the role of routine intravenous pyelography (IVP),
      rectoscopy and additional imaging techniques like computed tomography (CT) and
      abdominal ultrasonography (USG) for the evaluation of patients with endometrial
      cancer. MATERIALS AND METHODS: A total of 97 women with endometrial cancer (82
      endometrioid and 15 non-endometrioid type) of all stages (Stage I = 65, II = 14,
      III = 13, IV = 5) were included in the study. Of these, 50 women were admitted
      because of postmenopausal bleeding, 24 with irregular vaginal bleeding and 7 with
      pain and leucorrhea, whereas the others had no complaints. Only one patient had
      symptoms related to the gastrointestinal system, but none for the urinary system.
      Preoperative CT (n = 45), IVP (n = 78), rectoscopy (n = 46), and USG or
      colonoscopy (n = 37) were performed on our patients. All the women had total
      abdominal hysterectomy and bilateral salpingo-oophorectomy, with/without pelvic
      (n = 81) and paraaortic (n = 34) lymphonodectomy, and omentectomy (n = 35).
      RESULTS: In 39 of 45 women who had CT, it had no effect on the operation and did
      not facilitate the operation. In two women there were pathological findings on CT
      and some interventions (resection and anastomosis) were performed on the
      gastrointestinal tract in these patients. However, CT had overcome pathological
      findings related with the gastrointestinal or urinary systems in four women, who
      needed interventions to these systems during the operation. CT was not performed
      on six women who needed interventions to the gastrointestinal system during the
      operations. Three patients had pathological findings (fissure, external
      compression) in rectoscopy, but only one patient had ileo-transverstomy, in which
      rectoscopic finding had not predicted the necessity of that procedure. Out of 78
      IVP, the only finding was external compression to the bladder in 38 patients, and
      this finding had no contribution to the operation. Among women who had USG or
      colonoscopy (n = 37) performed, five had pathological findings that contributed
      to the extensiveness or the mode of the operations (liver nodules, polyps in the
      colon). CONCLUSIONS: Routine preoperative computed tomography, intravenous
      pyelography, rectoscopy or abdominal USG and colonoscopy have little impact on
      the decision and the prediction of the extensiveness of the operation.

PMID- 19112575
TI  - Vulvar and breast Paget's disease with synchronous underlying cancer: a unique
      association.
AB  - BACKGROUND: We report a unique case of Paget's disease of vulva and breast.
      Sequentially the patient had invasive ductal carcinoma of the breast, 5 years
      later was diagnosed with vulvar Paget's with underlying adenocarcinoma and after
      another 2 years was diagnosed with Paget's disease of the breast. CASE: A 58-year
      old woman with invasive ductal cancer of the left breast was treated with
      lumpectomy, lymph node dissection, radiation therapy and tamoxifen. Five years
      later and after complaints of longstanding vulvar pruritus, the patient was
      diagnosed with vulvar Paget's disease and treated with simple vulvectomy, which
      revealed a concurrent underlying adenocarcinoma. Subsequently there was
      recurrence of vulvar malignancy and wide local excision was performed. Seven
      years after the initial diagnosis of the breast cancer, a biopsy of a left
      areolar red, ulcerated lesion revealed Paget's disease of the breast. CONCLUSION:
      Physicians need to be cognizant of the rare occurrence of mammary and
      extramammary Paget's disease with underlying malignancies in both locations. A
      thorough physical examination including biopsy is essential for early detection
      and appropriate management.

PMID- 19112576
TI  - Severe acute obstetric morbidity (near-miss): a review of the relative use of its
      diagnostic indicators.
AB  - OBJECTIVE: To assess the most commonly employed diagnostic indicators of severe
      maternal morbidity (obstetric near-miss). METHODS: Review of the literature from
      January 1989 to August 2008. RESULTS: Fifty-one manuscripts met the eligibility
      criteria, and 96 indicators were utilized at least once. Admission to intensive
      care unit (n = 28 studies) was the indicator most frequently utilized, followed
      by eclampsia and hemorrhage (n = 27), blood transfusion (n = 26) and emergent
      hysterectomy (n = 24). CONCLUSION: Considering these findings, a trial version of
      a 13-item instrument for diagnosing obstetric near-miss is proposed. It includes
      the indicators eclampsia, severe hypertension, pulmonary edema, cardiac arrest,
      obstetrical hemorrhage, uterine rupture, admission to intensive care unit,
      emergent hysterectomy, blood transfusion, anesthetic accidents, urea >15 mmol/l
      or creatinine >400 mmol/l, oliguria (<400 ml/24 h) and coma. Further studies
      should focus on consensual definitions for these indicators and evaluate the
      psychometric proprieties of this trial version.

PMID- 19112577
TI  - Isthmic uterine fibroids: the dynamics of growth.
AB  - The isthmus of uterus is different from the rest of uterus and cervix in anatomic
      as well as functional aspects. The tumors arising from it may be subjected to a
      different set of forces which may predispose to growth in a tangential or
      horizontal direction. A young woman who underwent myomectomy for a large isthmic
      myoma is presented and the growth dynamics are discussed.

PMID- 19112578
TI  - Endometrial and follicular development following letrozole intervention in
      unexplained infertile patients failed to get pregnant with clomiphene citrate.
AB  - PURPOSE: This study is designed to evaluate and compare follicular phase
      parameters during ovarian stimulation with the clomiphene citrate (CC) and
      letrozole (LET) in unexplained infertile patients who failed to get pregnant
      following frequent CC-treated cycles. METHODS: A total of 64 unexplained
      infertile women who failed to get pregnant following frequent CC-treated cycles
      were studied for one CC-treated cycle (100 mg/day), 2 washout cycles, and then 1
      LET-treated cycle (5 mg/day). Number of follicles over 14 mm in diameter,
      diameter of the largest follicles, endometrial thickness, serum estradiol (E2)
      and LH levels were measured when one mature follicle over 18 mm in diameter
      detected during transvaginal ultrasonography. RESULTS: The mean value of the
      largest follicle diameter, number of developed follicles >14 mm, endometrial
      thickness and LH in LET-treated cycle was significantly higher than CC-treated
      cycle (P values were 0.007, <0.001, <0.001, and 0.004, respectively), whereas
      mean level of E2 showed a significantly lower level during LET-treated cycle (P <
      0.001). CONCLUSIONS: About 5 mg/day of LET is associated with better follicular
      phase parameters, endometrial development, serum E2 and LH levels in women with
      unexplained infertility who failed to get pregnant following frequent CC-treated
      cycles.

PMID- 19112579
TI  - Gibberellin precursor is involved in spore germination in the moss Physcomitrella
      patens.
AB  - Gibberellins are ent-kaurene derived phytohormones that are involved in seed
      germination, stem elongation, and flower induction in seed plants, as well as in
      antheridia formation and spore germination in ferns. Although ubiquitous in
      vascular plants, the occurrence and potential function(s) of gibberellins in
      bryophytes have not yet been resolved. To determine the potential role of
      gibberellin and/or gibberellin-like compounds in mosses, the effect of AMO-1618
      on spores of Physcomitrella patens (Hedw.) B.S.G. was tested. AMO-1618, which
      inhibited ent-kaurene and gibberellin biosynthesis in angiosperms, also inhibited
      the bifunctional copalyl diphosphate synthase (E.C. 5.5.1.13)/ent-kaurene
      synthase (E.C. 4.2.3.19) of P. patens. AMO-1618 also caused a decrease in spore
      germination rates of P. patens, and this inhibitory effect was less pronounced in
      the presence of ent-kaurene. These results suggest that ent-kaurene biosynthesis
      is required by P. patens spores to germinate, implying the presence of
      gibberellin-like phytohormones in mosses.

PMID- 19112580
TI  - Photosynthetic parameters of sexually different parts of Porphyra katadai var.
      hemiphylla (Bangiales, Rhodophyta) during dehydration and re-hydration.
AB  - Physiological data from extreme habitat organisms during stresses are vital
      information for comprehending their survival. The intertidal seaweeds are exposed
      to a combination of environmental stresses, the most influential one being
      regular dehydration and re-hydration. Porphyra katadai var. hemiphylla is a
      unique intertidal macroalga species with two longitudinally separated, color
      distinct, sexually different parts. In this study, the photosynthetic performance
      of both PSI and PSII of the two sexually different parts of P. katadai thalli
      during dehydration and re-hydration was investigated. Under low-grade dehydration
      the variation of photosystems of male and female parts of P. katadai were
      similar. However, after the absolute water content reached 42%, the PSI of the
      female parts was nearly shut down while that of the male parts still coordinated
      well and worked properly with PSII. Furthermore, after re-hydration with a better
      conditioned PSI, the dehydrated male parts were able to restore photosynthesis
      within 1 h, while the female parts did not. It is concluded that in P. katadai
      the susceptibility of photosynthesis to dehydration depends on the accommodative
      ability of PSI. The relatively lower content of phycobiliprotein in male parts
      may be the cause for a stronger PSI after severe dehydration.

PMID- 19112581
TI  - The bacterial Tn9 chloramphenicol resistance gene: an attractive DNA segment for
      Mos1 mariner insertions.
AB  - The eukaryotic mariner transposons are currently thought to have no sequence
      specificity for integration other than to insert within a TA contained in a
      degenerated [TA](1-4) tract, either in vitro or in vivo. We have investigated the
      properties of a suspected hotspot for the integration of the mariner Mos1
      element, namely the Tn9 cat gene that encodes a chloramphenicol acetyl
      transferase. Using in vitro and bacterial transposition assays, we confirmed that
      the cat gene is a preferential target for MOS1 integration, whatever its sequence
      environment, copy number or chromosomal locus. We also observed that its presence
      increases transposition rates both in vitro and in bacterial assays. The
      structural and sequence features that constitute the attractiveness of cat were
      also investigated. We first demonstrated that supercoiling is essential for the
      cat gene to be a hot spot. In contrast to the situation for Tc1-like elements,
      DNA curvature and bendability were not found to affect integration target
      preferences. We found that Mos1 integrations do not occur randomly along the cat
      gene. All TA dinucleotides that are preferred for integration were found within
      either TATA or TA x TA motifs. However, these motifs are not sufficient to
      constitute an attractive dinucleotide, since four TATA and TA x TA sites are cold
      spots.

PMID- 19112582
TI  - Air pollution and mutations in the germline: are humans at risk?
AB  - Genotoxic air pollution is ubiquitous in urban and industrial areas. A variety of
      studies has linked human exposure to air pollution with a number of different
      somatic cell endpoints including cancer. However, the potential for inducing
      mutations in the human germline remains unclear. Sentinel animal studies of
      germline mutations at tandem-repeat loci (specifically minisatellites and
      expanded simple tandem repeats) have recently provided proof of principle that
      germline mutations can be induced in vertebrates (birds and mice) by air
      pollution under ambient conditions. Although humans may also be susceptible to
      induced germline mutations in polluted areas, uncertainties regarding causative
      agents, doses, and mutational mechanisms at repetitive DNA loci currently
      preclude extrapolation from animal data to the evaluation of human risk.
      Nevertheless, several recent studies have linked air pollution exposure to DNA
      damage in human sperm, indicating that our germ cells are not impervious to the
      genotoxic effects of air pollution. Thus, both sentinel animal and human studies
      have raised the possibility that ambient air pollution may increase human
      germline mutation rates, especially at repetitive DNA loci. Given that some human
      genetic conditions appear to be modulated by length mutations at tandem-repeat
      loci (e.g. HRAS1 cancers, type 1 diabetes, etc.), there is an urgent need for
      extensive study in this area. Research should be primarily focused upon: (1) the
      direct measurement of mutation frequencies at repetitive DNA loci in human male
      germ cells as a function of air pollution exposure, (2) large-scale epidemiology
      studies of inherited disorders and tandem-repeat associated genetic conditions
      and air pollution, and (3) the characterization of mutational mechanisms at
      hypervariable tandem-repeat loci.

PMID- 19112583
TI  - Wild chimpanzees (Pan troglodytes schweinfurthii) distinguish between different
      scream types: evidence from a playback study.
AB  - When experiencing aggression from group members, chimpanzees commonly produce
      screams. These agonistic screams are graded signals and vary acoustically as a
      function of the severity of aggression the caller is facing. We conducted a
      series of field playback experiments with a community of wild chimpanzees in the
      Budongo Forest, Uganda, to determine whether individuals could meaningfully
      distinguish between screams given in different agonistic contexts. We compared
      six subjects' responses to screams given in response to severe and mild
      aggression. Subjects consistently discriminated between the two scream types. To
      address the possibility that the response differences were driven directly by the
      screams' peripheral acoustic features, rather than any attached social meaning,
      we also tested the subjects' responses to tantrum screams. These screams are
      given by individuals that experienced social frustration, but no physical threat,
      yet acoustically they are very similar to screams of victims of severe
      aggression. We found chimpanzees looked longer at severe victim screams than
      either mild victim screams or tantrum screams. Our results indicate that
      chimpanzees attend to the informational content of screams and are able to
      distinguish between different scream variants, which form part of a graded
      continuum.

PMID- 19112584
TI  - Simultaneous determination of mechanical properties and physiologic parameters in
      living rat brain.
AB  - Mechanical properties were determined in living adult rat brain. Reconstructed
      magnetic resonance images of the rat brain before and after 2 mm compression with
      a 4.06 mm diameter vinyl screw showed the total volumetric strain was maximal at
      the site of indentation. The pressure response to stepwise brain compression
      showed a linear relationship to the point of respiratory compromise. Instrumented
      indentation was performed on live brain with intact dura using a 4-mm-diameter
      flat punch indenter to a maximum depth 1.2 mm at loading-unloading rates not
      exceeding 0.34 N/min and 1.2 mm/min. The calculated elastic modulus showed no
      consistent change after death. Creep deformation over 15 s was 7.86+/-1.6% in
      live brain and 27.0+/-0.24% after death. In constant multicycle indentation,
      displacement from 1st to 10th cycle increased 8.0+/-1.7% in life and 12.9+/-2.8%
      after death. The results suggest that elastic properties of rat intracranial
      contents do not change immediately after death, while changes in the viscous
      properties are substantial. The process of measuring these properties can alter
      physiological parameters.

PMID- 19112585
TI  - Influence of metal addition on ethanol production with Pichia stipitis ATCC
      58784.
AB  - Trace metals always act as cofactors or coenzymes in many cellular processes.
      Deficiency or excess of some metals will affect the fermentation of
      lignocellulosic hydrolysate. In order to make sure the deficient or excessive
      states of metals in culture medium, metal contents analysis was conducted in
      Pichia stipitis ATCC 58784 cells, synthetic medium, and diluted acid hydrolysate
      of rice straw. The results showed that Cu, Ni, and Co were deficient, and Al was
      a little excessive. So the influences of Cu(2+), Al(3+), Ni(2+), and Co(2+)
      additions on the growth and ethanol production of ATCC 58784 were further
      researched. Low concentration additions of Cu(2+) and Al(3+) (<0.24 mM and <0.23
      mM, respectively) improved biomass growth of ATCC 58784 by 34 and 13%,
      respectively; however, higher concentrations decreased biomass growth. On the
      other hand, addition of Cu(2+) (0.39 mM) did not affect volumetric ethanol
      production significantly (P = 0.05) and addition of Al(3+) (0.38 mM) showed no
      influence on volumetric ethanol production (P = 0.68). Addition of 0.074 mM
      Co(2+) inhibited biomass growth of ATCC 58784 by 13% and volumetric ethanol
      production by 10%. The biomass growth and volumetric ethanol production of ATCC
      58784 was arrested by the addition of 0.33 mM of Ni(2+) by 53 and 65%,
      respectively.

PMID- 19112587
TI  - Evaluation of some pharmacological activities of ethanol extracts of seeds,
      pericarp and leaves of Eugenia Jamolana in rats.
AB  - The present study investigated the effect of ethanol extracts of seeds, pericarp
      and leaves of Eugenia Jamolana (E. Jamolana) on inflammation, gastric ulcer, anti
      oxidants and hepatoprotective in rats. The acute inflammation was induced by
      intra-plantar injection of carrageenan (100 microl of 1 %) in the rat hind paw.
      Gastric ulcer was evoked by indomethacin (25 mg/kg) oral administration. Liver
      damage was induced by given CCL4 (2.5 ml/kg) orally. The median lethal (LD(50))
      of the ethanol extract of both seeds and pericarp were determined and revealed
      that the investigated extracts of seeds and pericarp were non toxic up to 5 g/kg.
      The anti-inflammatory results showed that the oral administration of ethanol
      extract of E. Jamolana seeds (250, 500 mg/kg) showed significant inhibition of
      oedema formation in dose-dependent manner by -27.86, -41.23, -44.73, -51.78 % and
      by -63.16, -37.77, -47.04, -55.36 % at 1, 2, 3 and 4 h at 1, 2, 3 and 4 h,
      respectively. While the pericarp given at dose (500 mg/kg) exhibited significant
      inhibition of the oedema formation by -34.64, -21,8, 19.23 and -33.47 % at 1, 2,
      3 and 4 h, respectively post carrageenan injection as compared with saline
      control group. E. Jamolana leaves fraction 1 given orally at dose of 25 mg/kg,
      induced non significant change on oedema, while the oedema response was
      significantly inhibited by -25.14, -33.4, -20.57 and -26.46 % at 1, 2, 3 and 4 h,
      respectively in group of rats that received leaves fraction 2 at the same dose.
      Rats were given leaves fraction 3 extract showed inhibition of oedema formation
      by -4.48 % at 1(st) h post- carrageenan injection, while at 2(nd), 3(rd) and
      4(th) h showed non significant change on oedema formation. The acute gastric
      mucosal lesions was significantly reduced by given ethanol extract of E. Jamolana
      seeds, pericarp (250, 500 mg/kg) and leaves fractions 1, 2 and 3 (25 mg/kg)
      respectively in dose dependent manner, as compared with indomethacin treated
      group (control group). All tested extracts showed significant reduction in
      elevated serum ALT, AST and ALP levels as compared with CCl4 treated group. The
      ethanol extract of E. Jamolana seeds, pericarp and leaves fractions 1, 2, 3
      showed significant elevation of blood GSH level and significant reduction in
      elevated plasma lipid peroxides (MDA) as compared with CCl4 treated group. In
      conclusion we can see that the ethanol extracts of E. Jamolana of seeds, pericarp
      and leaves fractions showed anti-inflammatory, anti-ulcer, hepatoprotective and
      anti-oxidants activity.

PMID- 19112586
TI  - Anti-inflammatory activity of parthenolide-depleted Feverfew (Tanacetum
      parthenium).
AB  - Extracts of Tanacetum parthenium (L.) Sch. Bip., a plant known under the common
      name "Feverfew", contains the sesquiterpene lactone parthenolide, a potent skin
      sensitizer. To eliminate the risk of skin sensitization from Feverfew, we
      developed a parthenolide-depleted extract of Feverfew (PD-Feverfew) and
      determined its effectiveness as an anti-inflammatory agent. We confirmed that PD
      Feverfew was sufficiently depleted of parthenolide since PD-Feverfew did not
      inhibit TNF-alpha induced-NF-kappaB activity unlike parthenolide containing whole
      Feverfew. PD-Feverfew directly inhibited the activity of pro-inflammatory enzymes
      5-lipoxygenase, phosphodiesterase-3 and phosphodiesterase-4. PD-Feverfew
      inhibited the release of pro-inflammatory mediators nitric oxide, PGE(2) and TNF
      alpha from macrophages and TNF-alpha, IL-2, IFN-gamma and IL-4 from human
      peripheral blood mononuclear cells. Additionally, PD-Feverfew inhibited TPA
      induced release of PGE(2) from human skin equivalents. In vivo, PD-Feverfew
      inhibited oxazolone-induced dermatitis, and was more potent than whole Feverfew
      in reducing TPA-induced dermatitis. Finally the efficacy of PD-Feverfew was
      confirmed clinically by a reduction in erythema in a methyl nicotinate-induced
      vasodilation model. In conclusion, our results indicate that PD-Feverfew extracts
      have potent anti-inflammatory activity suggesting that this botanical would be
      efficacious in relieving inflammation without inducing immune sensitization.

PMID- 19112588
TI  - Social determinants of health - a cross-cultural perspective.

PMID- 19112589
TI  - Closing the global health gaps in a generation - how is it possible?

PMID- 19112590
TI  - Educational differences in functional limitations: comparisons of 55-65-year-olds
      in the Netherlands in 1992 and 2002.
AB  - OBJECTIVES: This study compares educational differences in the functional
      limitations of 55-65-year-olds in the Netherlands in 1992 and 2002 and examines
      whether changes are explained by cohort lifestyle and psychosocial changes.
      METHODS: Data from two cohorts of 55-65-year-olds (n = 948 in 1992 and n = 980 in
      2002) in the Longitudinal Aging Study Amsterdam are analysed. RESULTS: Men's
      disability ratios are similar in both cohorts. The women's disability ratio is
      higher in 2002 than in 1992. In 2002 the male and female cohorts both report
      unhealthier behavior than in 1992. Multivariate logistic regression analyses show
      that adjusted for age, cohort, lifestyle and psychosocial resources, poorly
      educated men have higher odds of functional limitations than well-educated men
      (OR = 2.62, 95% CI = 1.57-4.37). Analyses among women show a significant
      interaction effect between education and cohort. Poorly educated women have
      higher odds of functional limitations in 2002 than in 1992 (OR = 3.33, 95% CI =
      1.02-10.87). CONCLUSIONS: The results underscore the need for policies focused on
      improving the health and lifestyle of the poorly educated.

PMID- 19112591
TI  - The relationship of absolute poverty and bone mineral density in postmenopausal
      Iranian women.
AB  - OBJECTIVE: It is increasingly recognized that socioeconomic inequalities play an
      important role in bone health, with significantly higher fracture rates being
      reported in lower income groups. But the relationship between absolute poverty
      and bone mineral density (BMD) and/or osteoporosis has not been investigated.
      METHODS: A total of 1135 postmenopausal women under absolute poverty lines who
      received financial support from the Imam Khomeini Relief Foundation (IKRF) and
      406 randomly selected healthy postmenopausal women were screened for osteoporosis
      using BMD testing. RESULTS: At all BMD sites, women under the absolute poverty
      lines had the lowest mean BMD values (p < 0.0001). According to the WHO criteria,
      252 subjects under absolute poverty lines (22.4%) and 35 healthy postmenopausal
      women from the general population (8.7%) were considered osteoporotic (p <
      0.0001). After adjustment for lifestyle factors for osteoporosis in logistic
      regression models, absolute poverty was associated with the age-adjusted
      prevalence of femoral neck osteoporosis and lumbar osteoporosis [OR = 2.50 (CI,
      1.38-4.51; p = 0.002); OR = 2.40 (CI, 1.56-3.70; p < 0.0001), respectively].
      CONCLUSION: Postmenopausal women under the absolute poverty lines had lower BMDs
      at all skeletal sites, independent of established osteoporosis risk factors.

PMID- 19112592
TI  - Comparison of a short food-frequency questionnaire and derived indices with a
      seven-day diet record in Belgian and Italian children.
AB  - OBJECTIVES: To compare food group intakes and dietary indices estimated from a 14
      item food frequency questionnaire (FFQ) with a seven day diet record. METHODS:
      112 Belgian and 114 Italian children (11-12 years) completed the FFQ followed by
      a seven-day diary (FD) and a retest one week later. Dietary indices were
      calculated from the FFQ and the FD. RESULTS: Spearman's correlations between the
      FFQ items and the diary varied between -0.13 and 0.67. When comparing the FFQ
      with the FD an overestimation was found for most items. The Excess Index was
      significantly correlated with energy intake (respectively 0.35 and 0.25 for
      Belgian and Italian children); the Variety Index with fiber intake (0.26 for
      both) and Calcium intake (respectively 0.32 and 0.41); the Fiber Index with fiber
      intake (respectively 0.30 and 0.37) and the Calcium Index with Calcium intake
      (respectively 0.47 and 0.50). CONCLUSION: When the FFQ is used for estimating
      consumption frequencies, overestimation must be considered. The ability to rank
      individuals varies considerably between food items. The Calcium index can be
      useful in situations requiring brief dietary instruments. The value of the other
      indices is lower although still associations in the expected directions were
      found.

PMID- 19112593
TI  - Sociodemographic and socioeconomic variations in leisure time physical activity
      in a sample of Hungarian youth.
AB  - OBJECTIVES: The main goal of the present study is to detect the relationship
      between youth's leisure time physical activity and a set of sociodemographic
      (age, gender, family stucture) and socioeconomic variables (SES and parental
      schooling). METHODS: Data were collected among Hungarian youth (middle and high
      school students, N = 1662) aged between 10-20 years using a self-administered
      questionnaire. RESULTS: Our findings did not indicate gender differences during
      the years of middle school, whereas gender differences became significant during
      the years of high school. In multivariate analyses, parental schooling played a
      decisive role in youth's physical activity, wheres SES self-assessment did not
      remain significant. CONCLUSION: These findings provide some useful information on
      characteristics of the target groups for health education programs.

PMID- 19112594
TI  - Counteracting obesity: developing a policy framework to guide action.
AB  - OBJECTIVES: The purpose of this paper is to stimulate further debate regarding
      possible courses of policy action aimed at preventing obesity. Gostin's framework
      for classifying antiobesity legal interventions is tested and extended to
      incorporate non-legislative policy initiatives to include a comprehensive array
      of policy actions available to deal with obesity. METHODS: A web search of the
      literature has been conducted. Initiatives from USA, Canada and the European
      Union were discussed in terms of their objectives and fit with the framework.
      RESULTS: Gostin's framework was found to be a useful tool in organizing all the
      initiatives (legislative and non-legislative). However, sometimes a broader
      definition of the category was needed. As well, in some categories, few
      initiatives were implemented to date and several new categories have to be added
      to the framework to classify all the existing initiatives. CONCLUSIONS: The
      theoretical developed framework will assist new initiatives assess possible
      courses of action as well as countries or organizations that have already
      implemented some measures identify what else can be done to effectively fight
      overweight and obesity.

PMID- 19112595
TI  - Conceptualising policy options for obesity prevention - response to
      "Counteracting obesity: developing a policy framework to guide action".

PMID- 19112596
TI  - Curbing the obesity epidemic: the need for policy action in a risk-balanced,
      orchestrated, comprehensive strategy.

PMID- 19112597
TI  - Classifying of strategies and measures against overweight and obesity: a
      controversial issue.

PMID- 19112598
TI  - Biodegradation and removal of pharmaceuticals and personal care products in
      treatment systems: a review.
AB  - Pharmaceuticals and personal care products (PPCPs) have been the focus of much
      recent research as concerns rise about their occurrence in bodies of water
      worldwide. In an effort to characterize the risk and determine the prevalence of
      these micropollutants in lakes and rivers, many researchers are examining PPCP
      removal from impaired water during wastewater treatment and water recycling (soil
      passage) processes. Biodegradation studies and projects considering combinations
      of biodegradation and other removal processes have been conducted over a wide
      range of compound categories and therapeutic classes, as well as across different
      systems and scales of study. This review summarizes the extent of PPCP removal
      observed in these various systems.

PMID- 19112599
TI  - A gene expression signature that defines breast cancer metastases.
AB  - The most important predictor of prognosis in breast cancer is lymph node status,
      yet little is known about molecular changes associated with lymph node
      metastasis. Here, gene expression analysis was performed on primary breast (PBT)
      and corresponding metastatic lymph node (MLN) tumors to identify molecular
      signatures associated with nodal metastasis. RNA was isolated after laser
      microdissection from frozen PBT and MLN from 20 patients with positive lymph
      nodes and hybridized to the microarray chips. Differential expression was
      determined using Mann-Whitney testing; Bonferroni corrected P values of 0.05 and
      0.001 were calculated. Results were validated using TaqMan assays. Fifty-one
      genes were differentially expressed (P < 1 x 10(-5), less than twofold
      differences) between the PBT and paired MLN; 13 with significantly higher
      expression in the MLN and 38 in the PBT. qRT-PCR validated the differential
      expression of 40/51 genes. Of the 40 validated genes, NTS and PAX5 were found to
      have >100-fold higher expression in MLT while COL11A1, KRT14, MMP13, TAC1 and
      WNT2 had >100-fold higher expression in PBT. Gene expression differences between
      PBT and MLN suggests that expression of a unique set of genes is required for
      successful lymph node colonization. Genes expressed at higher levels in PBT are
      involved in degradation of the extracellular matrix, enabling cells with
      metastatic potential to disseminate, while genes expressed at higher levels in
      metastases are involved in transcription, signal transduction and immune
      response, providing cells with proliferation and survival advantages. These data
      improve our understanding of the biological processes involved in successful
      metastatis and provide new targets to arrest tumor cell dissemination and
      metastatic colonization.

PMID- 19112600
TI  - Leptin utilizes Jun N-terminal kinases to stimulate the invasion of MCF-7 breast
      cancer cells.
AB  - In breast tumors, high levels of leptin have been associated with increased
      incidence of breast cancer metastasis. Breast cancer metastasis is directly
      associated with breast cancer cell invasion. However, whether leptin could
      augment breast cancer cell invasion is not known. Here we showed that leptin
      increased the invasiveness and the matrix metallo-proteinase-2 (MMP-2) activity
      of the MCF-7 breast cancer cell line. Leptin stimulated the phosphorylation of
      extracellular signals regulated kinases, signal transducers and activators of
      transcription 3 and Jun N-terminal kinases (JNK); however, only inhibition of JNK
      decreased leptin-mediated activation of MMP-2. Furthermore, inhibition of JNK
      suppressed leptin-mediated breast cancer cell invasion. Here we report the novel
      findings that leptin increased invasion of breast cancer cells by activating JNK,
      resulting in increased MMP-2 activity.

PMID- 19112601
TI  - Role of PKCbeta in hepatocellular carcinoma cells migration and invasion in
      vitro: a potential therapeutic target.
AB  - Considerable interests have recently been focused on mechanism of human
      hepatocellular carcinoma (HCC) metastasis-the most fundamental characteristics of
      HCC and the ultimate cause of most HCC mortality, so screening more potential
      early prognostic marker and therapeutic target is urgent. In this study, we
      screened genome of three HCC cell lines with consistently increased metastatic
      potentials and sharing same genetic background, through DNA microarray and found
      consecutively up-regulated expression of PKCbeta in these cell lines compared to
      others PKCs, which was reconfirmed by real time RT-PCR and western blot analysis.
      Moreover, it was found, after efficient silence of PKCbeta by RNAi assay or
      inhibition of PKCbeta activity by a specific inhibitor LY317615, migration and
      invasion of HCC cells significantly decreased. In addition, depletion of PKCbeta
      protein significantly reversed the enhancement of PMA-stimulated HCC migration
      and invasion ability in vitro. All the data suggest a key role of PKCbeta in HCC
      motility and PKCbeta may be a potential therapeutic target.

PMID- 19112602
TI  - Transcranial doppler sonography is useful for the decision-making at the point of
      care in patients with acute hepatic failure: a single centre's experience.
AB  - Acute hepatic failure (ALF) is an uncommon disease characterized by a rapid
      deterioration of the hepatic function with severe derangements of the mental
      status in previously healthy subjects due to massive hepatocytes necrosis.
      Neurological impairment, due to intracranial hypertension and cerebral ischemia,
      is a key factor because it is a main criterion to decide when to proceed to liver
      transplantation, which is only treatment for these patients. Therefore,
      neurological monitoring holds an essential role in the clinical management of ALF
      patients but it needs to be performed at the point-of-care in the majority of the
      cases as such critically ill patients cannot be moved away from the ICU because
      they frequently need continuous hemodynamic, ventilatory and renal support. We
      herein report and discuss our experience relating to the use of transcranial
      sonography as a neuro-monitoring tool in ALF patients. In our series this
      technique allowed a repeatable and reliable non-invasive assessment of cerebral
      blood flow changes at the bedside thus avoiding the complications associated with
      the use of an intracranial probe to measure intra-cranial pressure and making it
      possible to correctly evaluate the timing and feasibility of liver
      transplantation.

PMID- 19112603
TI  - Cancer registration data and quality indicators in low and middle income
      countries: their interpretation and potential use for the improvement of cancer
      care.
AB  - Cancer registration data plays a major role in the design and monitoring of
      cancer control activities and policies, and population-based cancer registries
      (PBCR) are the main source of information. In developed countries, the healthcare
      infrastructure enables the registration of quality cancer data. In low and middle
      Income countries (LMIC), where health care facilities are limited or scarce,
      cancer registration data may be of low quality. The aim of this article is to
      demonstrate the value of cancer incidence data for LMIC, even when quality is
      questionable, as well as to attempt to interpret the messages that the quality
      indicators convey both for cancer registration and the healthcare system. The
      study of data submitted to the Cancer incidence in five continents, volume nine
      (CI5-IX) leads to the conclusion that when PBCR from LMIC cannot provide good
      quality data it may indicate a deficiency that goes above and beyond the
      registrar ability. The quality control indicators evaluated provide insight on
      local conditions for cancer diagnosis and care. Low data quality not only signals
      lack of collaboration among reporting sources and the inability of the registrar
      to perform quality abstracting, but also points to specific weaknesses of the
      cancer care system and can guide improvement goals and efforts.

PMID- 19112604
TI  - The beta-tubulin gene as a molecular phylogenetic marker for classification and
      discrimination of the Saccharomyces sensu stricto complex.
AB  - The Saccharomyces sensu stricto complex comprises seven very closely related
      species. In this study, we compared the use of two different phylogenetic
      markers, the 26S rDNA and beta-tubulin genes, for discriminating phylogenetic
      relationships among Saccharomyces sensu stricto strains using sequencing as well
      as RFLP methods. The average sequence similarity for the beta-tubulin gene
      (90.0%) among seven strains was significantly less than that for 26S rDNA
      (98.6%). This result demonstrates that beta-tubulin gene sequences provided
      higher resolution than 26S rDNA sequences. Species-specific restriction profiles
      of the Saccharomyces strains were obtained by cutting them with the Tsp509I
      enzyme. Our data indicate that phylogenetic relationships between these strains
      are best resolved using sequencing or RFLP analysis of the beta-tubulin gene.

PMID- 19112607
TI  - Subcritical crack growth in porcelains, glass-ceramics, and glass-infiltrated
      alumina composite for dental restorations.
AB  - The objective was to compare fracture toughness (K(Ic)), stress corrosion
      susceptibility coefficient (n), and stress intensity factor threshold for crack
      propagation (K(I0)) of two porcelains [VM7/Vita (V) and d.Sign/Ivoclar (D)], two
      glass-ceramics [Empress/Ivolcar (E1) and Empress2/Ivlocar (E2)] and a glass
      infiltrated alumina composite [In-Ceram Alumina/Vita (IC)]. Disks were
      constructed according to each manufacturer's processing method, and polished
      before induction of cracks by a Vickers indenter. Crack lengths were measured
      under optical microscopy at times between 0.1 and 100 h. Specimens were stored in
      artificial saliva at 37 degrees C during the whole experiment. K(Ic) and n were
      determined using indentation fracture method. K(I0) was determined by plotting
      log crack velocity versus log K(I). Microstructure characterization was carried
      out under SEM, EDS, X-ray diffraction and X-ray fluorescence. IC and E2 presented
      higher K(Ic) and K(I0) compared to E1, V, and D. IC presented the highest n
      value, followed by E2, D, E1, and V in a decreasing order. V and D presented
      similar K(Ic), but porcelain V showed higher K(I0) and lower n compared to D.
      Microstructure features (volume fraction, size, aspect ratio of crystalline
      phases and chemical composition of glassy matrix) determined K(Ic). The increase
      of K(Ic) value favored the increases of n and K(I0).

PMID- 19112605
TI  - Two specific strains of Histoplasma capsulatum causing mucocutaneous
      manifestations of histoplasmosis: preliminary analysis of a frequent
      manifestation of histoplasmosis in southern Brazil.
AB  - OBJECTIVES: Skin lesions, uncommon in US cases (<10%), occur in 38-85% of cases
      reported from Latin America. Although these differences may reflect reporting
      bias, delayed diagnosis, or differences in host immune response among different
      ethnic groups, they also could result from genetic differences changing the
      pathobiology of the organism. It is possible that genetic differences among
      strains of H. capsulatum may influence the pathogenesis and clinical
      manifestations of histoplasmosis. METHODS: We examined the clinical features of
      patients with mucocutaneous manifestations of histoplasmosis and performed
      genetic analysis based on nucleotide sequence variations in the internal
      transcribed spacer regions of rRNA genes of H. capsulatum isolates of patients.
      Two pairs of PCR primers were designed to develop and amplify the ITS regions of
      H. capsulatum, 5'-TACCCGGCCACCCTTGTCTA-3' and 5'-AGCGGGTGGCAAAGCCC-3'. These
      primers were based on the ITS sequence of Ajellomyces capsulatus, the
      ascomycetous teleomorph form of H. capsulatum, deposited in the GenBank
      (accession number U18363). Eight patients attending a tertiary-care hospital in
      southern Brazil were enrolled into the study. All case patients had skin cultures
      growing H. capsulatum at the mycology laboratory. RESULTS: Six of eight (75%)
      patients were HIV-positive and presented involvement of multiples organs by H.
      capsulatum. Two HIV-negative patients did not present evidence of involvement of
      other organs besides mucosa and skin. ITS sequencing of a DNA H. capsulatum
      fragment of 485-bp from isolates of 8 patients revealed two distinct strains. The
      2 distinct fragments (Hc1, Hc2) differed from each other at 7 positions in the
      ITS regions. They were identical to strains of H. capsulatum isolated in patients
      from Colombia and Argentina, but different from strains isolated in US. Hc1 and
      Hc2 were isolated in 5 patients and 3 patients, respectively, with mucocutaneous
      manifestations of histoplasmosis. Both Hc1 and Hc2 strains were isolated in HIV
      infected and non-HIV-infected patients. CONCLUSIONS: Mucocutaneous manifestations
      of histoplasmosis, which are frequently seen in Brazilian patients were caused by
      2 specific strains in our institution. Those strains have been isolated in
      patients with these particular clinical features of histoplasmosis in Latin
      America. Our study suggests that unique pathogenic characteristics among the
      Latin American species of H. capsulatum might explain its increased
      dermatotropism.

PMID- 19112610
TI  - The unmet educational agenda in integrated care.
AB  - One of the reasons integrated care has not become a dominant service delivery
      model is the unmet training agenda. This article argues that the typical mental
      health professional is not trained to adequately address the challenges of
      integrated care. To insure competency both a macro and clinical training agenda
      are needed. At the macro-level, mental health professionals need to understand
      healthcare economics and basic business principles as any integrated care service
      delivery system is embedded and driven by economic forces. Integrated care
      practitioners also need some basic business skills to understand these forces and
      to create and manage a financially viable system, given the future flux of the
      system. Traditional mental health professionals also do not have the clinical
      skills to implement integrated care. Integrated care is not simply placing a
      traditionally trained mental health professional and letting them practice
      specialty mental health in a medical setting. Thus, the special skills needed in
      integrated care are enumerated and discussed. Finally, a new degree program is
      described as it is time given the huge need and advantages of integrated care to
      develop specialty training in integrated care.

PMID- 19112608
TI  - Quantification of bone mass gain in response to the application of biphasic
      bioceramics and platelet concentrate in critical-size bone defects.
AB  - Biphasic bioceramics have been widely indicated for bone reconstruction; however,
      the real gain in bone mass due to the presence of such biomaterials has not been
      established yet nor the advantages of its association with platelet concentrate.
      This study aims at quantifying the volume of bone matrix, osteoblasts,
      osteocytes, blood vessels and adipose tissue after the application of a biphasic
      bioceramics composed of 65% hydroxyapatite and 35% beta-tricalcium phosphate.
      Critical-size bone defects were produced in rabbit femora and reconstructed with
      bioceramics only, with bioceramics combined with platelet concentrate, with
      platelet concentrate alone, and with no treatment (blood clot). The quantitative
      evaluation was performed on histological sections using histomorphometry. Our
      data provide original evidence that consolidates the indication of bioceramics
      for clinical bone loss reconstruction. The application of biphasic bioceramics
      alone led to major bone mass gain and was followed by its association with
      platelet concentrate. On the other hand, platelet concentrate can contribute to
      the augmentation and maintenance of the adipose tissue, representing a new field
      for future applications in plastic surgery.

PMID- 19112609
TI  - Trimethyl chitosan and its applications in drug delivery.
AB  - Chitosan, a polymer obtained by deacetylation of chitin is widely studied for its
      pharmaceutical and nonpharmaceutical applications. Recommendations about uses of
      this polymer although could not be always realized due to limited solubility.
      Chitosan, for example, has been extensively evaluated for its mucoadhesive and
      absorption enhancement properties. The positive charge on the chitosan molecule
      gained by acidic environment in which it is soluble seems to be important for
      absorption enhancement. However chitosan is not soluble in medium except below pH
      5.6. This limits its use as permeation enhancer in body compartments where pH is
      high. In this regard there is a need for chitosan derivatives with increased
      solubility, especially at neutral and basic pH values. Trimethylation of chitosan
      is an effort in this direction. Despite the abundance of the research related to
      trimethyl chitosan (TMC), the overview of the topic is not available. Hence an
      attempt is made in this review to cover the recent findings pertaining to
      synthesis, characterization and applications of TMC especially in pharmaceutical
      field. TMC has been synthesized by different ways and characterized by FTIR, NMR,
      DSC etc. This quaternized derivative of chitosan possesses a positive charge and
      is soluble over a wide range of pH. TMC, being a derivative of cationic polymer
      enriched with positive charge shows better mucoadhesive, permeation enhancement,
      drug delivery and DNA delivery properties. TMC can be further derivitized or
      grafted for modulating properties as solubility, cytotoxicity or cell recognition
      ability. Apart from these applications, TMC itself and its derivatives exhibit
      antimicrobial properties also. Quaternization of chitosan not only with methyl
      group but higher group as ethyl or along with spacer or quaternization of
      modified chitosan can be of interest too.

PMID- 19112611
TI  - Molecular characterization of canine parvovirus-2 variants circulating in
      Tunisia.
AB  - Canine parvovirus type 2 (CPV2) emerged in 1978 as a highly contagious and very
      serious disease in dogs. The characterization of CPV2 antigenic types is
      exclusively based on the identification of the amino acid residue at position 426
      of the capsid protein VP2. Currently, three antigenic types CPV-2a (asparagine
      N(426)), CPV-2b (aspartic acid D(426)) and CPV-2c (glutamic acid E(426)) are
      circulating worldwide. In Tunisia, despite the fact that many clinical and few
      serological investigations clearly indicate that CPV is widespread and of major
      concerns in the local dog population, no molecular and antigenic type
      characterization of circulating variants has been carried out. This investigation
      showed that most of clinically presumed CPV infections were confirmed by
      classical or real-time PCR. When no real-time PCR facilities were affordable,
      classical PCR as reported here in association with restriction fragment length
      polymorphism (RFLP) with MboI and MboII can be very useful for screening and
      diagnosing CPV infections. A total of 50 variants were characterized by
      sequencing and an almost even representation of the different antigenic types,
      including CPV-2c and slightly more type 2b, were evidenced. Characterization of
      the Tunisian variants by MGB probe assays as reported was inefficient for most of
      CPV-2a variants because of their typical nucleotide mutation C(1269).
      Phylogenetic analysis showed that the Tunisian variants underwent evolution for a
      relatively long period of time inside the country. The analysis also showed some
      crossings of the different antigenic types, leaving both genotypic and phenotypic
      characteristic mutations.

PMID- 19112612
TI  - Genetic diversity and distribution of tomato-infecting begomoviruses in Iran.
AB  - The incidence and severity of tomato leaf curl disease (TLCD) is increasing
      worldwide. Here we assess the diversity and distribution within tomato producing
      areas of Iran of begomoviruses that cause this disease. Tomato with typical TLCD
      symptoms and asymptomatic weeds were collected in 2005 and 2006 and tested for
      the presence of begomovirus DNA using polymerase chain reaction (PCR). Analysis
      of cloned and sequenced PCR products revealed that both mono- and bipartite
      begomoviruses are associated with TLCD in Iran. Furthermore, our results
      confirmed the symptomless infection with mono- and bipartite begomoviruses of two
      weed species, Chrozophora hierosolymitana Spreng (Euphobiaceae) and Herniaria sp.
      (Caryophyllaceae). Eighteen Iranian begomovirus isolates were classified into two
      major groups and two or three subgroups according to the 5'-proximal 200
      nucleotides of the coat protein (CP) gene or the N-terminal 600 nucleotides of
      the Rep gene. Whereas most of the monopartite isolates showed closest similarity
      to tomato yellow leaf curl virus-Gezira (TYLCV-Ge), the three bipartite isolates
      were most similar to Tomato leaf curl New Delhi virus (ToLCNDV). Mixed mono- and
      a bipartite begomovirus infections were detected in both tomato and C.
      hierosolymitana. Our results indicate that the tomato producing areas in central,
      southern, and southeastern Iran are threatened by begomoviruses originating from
      both the Mediterranean basin and the Indian subcontinent.

PMID- 19112614
TI  - Similarities in drinking behavior of twin's friends: moderation of heritability
      of alcohol use.
AB  - Previous research has indicated that friends' drinking may influence alcohol use
      in adolescents and young adults. We explored whether similarities in the drinking
      behavior of friends of twins influence the genetic architecture of alcohol use in
      adolescence and young adulthood. Survey data from The Netherlands Twin Register
      were available for 1,526 twin pairs aged 16-25 years. We categorized the twin
      pairs as concordant (both report similar alcohol use in their friends) or
      discordant for the alcohol use of their friends. Genetic moderator models were
      tested by carrying out multi-group analyzes in Mplus. Findings showed a
      significant moderation effect. Genetic factors were more and common environment
      less important in the explanation of variation in alcohol use in twins discordant
      for alcohol use of friends than in twins concordant for alcohol use of friends.

PMID- 19112613
TI  - The effect of assumptions about parental assortative mating and genotype-income
      correlation on estimates of genotype-environment interaction in the National
      Merit Twin Study.
AB  - In a previous paper (Harden et al. in Behav Gen 37:273-283, 2007) models of
      genotype-environment interaction were fitted to data from the National Merit Twin
      Study, resulting in evidence for an interaction: the heritability of National
      Merit Qualifying Test scores increased at higher levels of family income. The
      present paper investigates two assumptions made in the previous modeling. These
      were a lack of resemblance between parents for cognitive skill, and possible
      correlations between family income and a child's genes because of the
      contribution of parental genes to both. The assumptions were found not to
      seriously affect estimates of the interaction effect-heritability still increased
      with income-but they did make a difference for other parameter estimates from the
      modeling. One possible explanation of the observed interaction, decreasing levels
      of assortative mating at higher income levels, was examined and found not to be
      consistent with other evidence from the study. Another possible explanation, a
      greater freedom of members of DZ pairs at higher income levels to follow
      independent interests, remained plausible.

PMID- 19112615
TI  - Patterns and predictors of early recurrence in postmenopausal women with estrogen
      receptor-positive early breast cancer.
AB  - Previous studies suggest that disease recurrence peaks at around 2 years in
      patients with early stage breast cancer (EBC), but provide no data regarding
      recurrence type. This retrospective analysis aimed to identify early recurrence
      types and risk factors in estrogen receptor-positive (ER+) EBC patients treated
      with adjuvant tamoxifen following breast cancer surgery. Postmenopausal women
      diagnosed with ER+ EBC from 1995 to 2004 were evaluated. Annual hazard ratios
      (HR) for recurrence at different sites were calculated. Time-dependent Cox
      regression analysis was used to identify predictors of recurrence within 2.5
      years of diagnosis, including factors that were more strongly predictive of early
      than later recurrence. Of 3,614 patients evaluated, 476 developed recurrence
      during the 5-year median follow-up. Cumulative recurrence rates at 2.5 years (95%
      confidence interval) were: overall 6.3% (5.5-7.1), locoregional 1.1% (0.7-1.5),
      contralateral 0.5% (0.3-0.7), and distant 4.8% (4.0-5.6). The annual HR of
      overall recurrence peaked at 2 years (4.3% per annum). The majority of this peak
      represented distant recurrence (3.4% per annum). In Cox regression analysis,
      tumor size and grade, lymph node involvement, lymphovascular invasion, and
      symptomatic presentation were significant independent predictors of early
      recurrence. Age at diagnosis was independently predictive of recurrence within
      2.5 years of diagnosis but not later recurrence. This study identified an early
      recurrence peak at 2 years, most of which were distant recurrences. Implementing
      an aromatase inhibitor after an initial 2-3 years of tamoxifen fails to address
      this early peak of distant recurrence and the potential breast cancer-associated
      mortality.

PMID- 19112616
TI  - Kwan's arm problem scale: psychometric examination in a sample of stage II breast
      cancer survivors.
AB  - Arm/shoulder problems and lymphedema are common in patients treated for breast
      cancer. The Kwan's arm problem scale (KAPS) is a 13 items self-rating form
      developed for examination of such problems. Since no such testing has been done,
      we wanted to examine the psychometric properties of the KAPS. At a median of 47
      months (range 32-87 months) post-surgery, 256 stage II breast cancer survivors
      filled in the KAPS. Findings from physical examination of arm/shoulder function,
      assessment of lymphedema, and established measures of quality of life (QOL),
      mental distress and fatigue were used to study convergent and discriminant
      validity. Factor structure and internal consistency were tested in split-half
      samples. The total KAPS as well as its two subscales showed high internal
      consistency (alpha > or = 0.92). A two factor solution explained 70% of the
      variance in the total KAPS score. Convergent validity was shown as the total KAPS
      score explained 32.5% of the variance in abduction of the ipsilateral shoulder.
      Discriminant validity was shown as the total KAPS score explained only 6.7% of
      the variance in abduction of the contralateral shoulder. Concurrent validity was
      confirmed since the total KAPS explained 54.8% of the variance in arm symptom
      subscale of breast cancer-specific QOL. Area under the curve was 0.80 for
      problems of using the arm at a cut-off of the total KAPS score of 21.5. The
      results show that the KAPS has good psychometric properties supported by high
      reliability and considerable convergent and discriminant validity.

PMID- 19112617
TI  - Sea of dreams.

PMID- 19112618
TI  - Proceedings of the 8th European Conference on Applications of Meteorology,
      September 2007, Madrid, Spain.

PMID- 19112620
TI  - [Surgery of paranasal sinuses -- endonasal surgery of paranasal sinuses. I].

PMID- 19112619
TI  - Current awareness in phytochemical analysis.

PMID- 19112623
TI  - 400 m pounds spending limit forced on NHS.

PMID- 19112624
TI  - Statistics lay bare inequalities in care.

PMID- 19112626
TI  - On seismic rumblings.

PMID- 19112625
TI  - How are top-ups going to affect your services?

PMID- 19112628
TI  - Data briefing. Same-day care sees admissions level off.

PMID- 19112627
TI  - A release from inadequate care.

PMID- 19112629
TI  - A bit of give and take.
AB  - The U.K. is short of organs for transplant. Presumed consent raises issues about
      mental capacity and language skills, and religious questions. There are concerns
      presumed consent could make doctors too quick to pronounce a patient dead.

PMID- 19112630
TI  - The 70 bn pound question.

PMID- 19112632
TI  - Ways to weed out inequality.

PMID- 19112631
TI  - A taste of each other's medicine.

PMID- 19112633
TI  - [Organizational, clinical and hygienic problems in additional medical examination
      of workers].
AB  - Presented materials deal with importance of additional medical examination,
      thorough medical examinations of workers exposed to occupational hazards and with
      suggestions on improvement in this sphere.

PMID- 19112634
TI  - [Diagnosis, expert examination and prevention of occupational neurosensory
      deafness in workers of oil producing and petrochemical industries].
AB  - The authors designed a complex of informative criteria for diagnosis and medical
      examination of occupational neurosensory deafness, in order to objectively form
      risk groups of ear diseases. The article deals with justified adequate
      therapeutic and prophylactic recommendations on primary and secondary prevention,
      that enable better quality of preliminary and periodic medical examinations of
      workers exposed to occupational noise.

PMID- 19112635
TI  - [Spermicidal properties of major environmental pollutants assigned to
      polychlorbiphenyls class].
AB  - The authors considered accumulation of environmental pollutants assigned to
      polychlorbiphenyls class in fat tissue and reproductive organs of male rats,
      discovered major accumulation of the pollutants in epididymis, demonstrated
      significant changes in cellular contents and functional properties of sperm.

PMID- 19112636
TI  - A boy, a bug, and a bite: a toddler with an inflamed lesion.

PMID- 19112637
TI  - Bad vaccine reactions deter some.

PMID- 19112638
TI  - E-documentation impacts patient care?

PMID- 19112639
TI  - NHS braced for the worst of darling's 5 bn pound spending cull.

PMID- 19112640
TI  - Pressure on to pick a winning combination.

PMID- 19112641
TI  - On customer confidence.

PMID- 19112642
TI  - In the best and worst of times.

PMID- 19112643
TI  - Data briefing. What is causing GP referrals to rise?

PMID- 19112644
TI  - Priority setting. The big C. Head above the noise.
AB  - Cancer has been a government health priority since the early 1990s. Spending on
      cancer could be at the expense of other needs, such as palliative care. The
      public lacks clear information about primary care trust spending decisions.

PMID- 19112645
TI  - Give lifesaving care at a stroke.

PMID- 19112646
TI  - Arm yourself with the right image.

PMID- 19112647
TI  - Constituents and antimicrobial properties of blue honeysuckle: a novel source for
      phenolic antioxidants.
AB  - The fruit of Lonicera caerulea L. (blue honeysuckle; Caprifoliaceae) and its
      phenolic fraction were analyzed for nutrients and micronutrients. The phenolic
      fraction was prepared from berries percolated with 0.1% H3PO4 and SPE using
      Sepabeads SP207. The sugar and lipid content was analyzed by HPLC and GC-MS. The
      total content of anthocyanins was determined using the pH differential absorbance
      method and aliphatic acids by capillary electrophoresis. MicroLC-MS/MS was used
      for determination of cyanidin-3-glucoside (the predominant anthocyanin), 3,5
      diglucoside, and 3-rutinoside, paeonidin-3-glucoside, 3,5-diglucoside, and 3
      rutinoside, delphinidin-3-glucoside and 3-rutinoside, pelargonidin-3-glucoside,
      3,5-diglucoside, and 3-rutinoside, quercetin, its 3-glucoside, and 3-rutinoside,
      epicatechin, protocatechuic, gentisic, ellagic, ferulic, caffeic, chlorogenic,
      and coumaric acids. The phenolic fraction displayed Folin-Ciocalteu reagent
      reducing (335 +/- 15 microg of gallic acid equivalent/mg) and DPPH and superoxide
      scavenging activity (IC50 12.1 +/- 0.1 and 115.5 +/- 6.4 microg/mL) and inhibited
      rat liver microsome peroxidation (IC50 160 +/- 20 microg/mL). The freeze-dried
      fruit and its phenolic fraction reduced the biofilm formation and adhesion to the
      artificial surface of Candida parapsilosis, Staphylococcus epidermidis,
      Escherichia coli, Enterococcus faecalis, and Streptococcus mutans.

PMID- 19112648
TI  - A plastic surgeon retires--due to illness.

PMID- 19112649
TI  - FDA notifications. Darunavir label has these changes.

PMID- 19112650
TI  - What next for UNAIDS?

PMID- 19112651
TI  - Celebrating 10 years of hESC lines: an interview with Alan Trounson.

PMID- 19112652
TI  - Celebrating 10 years of hESC lines: an interview with Rudolf Jaenisch.

PMID- 19112653
TI  - Is preoperative anxiety and depression associated with onset of delirium after
      cardiac surgery in older patients? A prospective cohort study.
AB  - OBJECTIVES: To investigate the prevalence of preoperative anxiety and depressive
      symptoms and their relationship with the occurrence of postcardiac delirium and
      to describe the evolution of these symptoms from preoperative admission until
      discharge. DESIGN: Descriptive, prospective, longitudinal study. SETTING: The
      intensive care unit and two cardiac surgery units in a university hospital
      setting. PARTICIPANTS: One hundred four patients (median age 71; 78.8% men)
      admitted for elective cardiac surgery. MEASUREMENTS: Anxiety measured
      preoperatively using the State-Trait Anxiety Inventory (STAI) and the Hospital
      Anxiety and Depression Scale (HADS); depression using the HADS; cognitive
      functioning using the Mini-Mental State Examination (MMSE); delirium using the
      Confusion Assessment Method (CAM), the CAM for the Intensive Care Unit (CAMICU),
      and the Delirium Index (DI); and activities of daily living using the Katz index
      of activities of daily living (Katz ADL scale). MMSE, CAM/CAM-ICU, and DI were
      obtained on postoperative Days 1, 3, and 7. On Day 7 and at discharge, the STAI,
      HADS, and Katz ADL scale were repeated. RESULTS: Postoperative delirium occurred
      in 26%; 55.8% reported preoperative state anxiety, 25.2% generalized anxiety, and
      15.5% depressive symptoms, but no association was found with delirium occurrence.
      Based on multivariable analysis, prolonged intubation time (odds ratio (OR)51.10,
      CI: 1.05-1.15, P5.001) and a low intraoperative lowest body temperature (OR50.86,
      CI: 0.74-0.99, P5.03) were independent predictors of delirium onset. At
      discharge, 35.7% and 12.2% of patients reported state anxiety and generalized,
      and 15.3% reported depressive symptoms. CONCLUSION: Despite the high prevalence
      of preoperative anxiety and depressive symptoms in older patients with cardiac
      surgery, no association was found with postoperative delirium.

PMID- 19112654
TI  - Successful dissemination of a community-based strength training program for older
      adults by peer and professional leaders: the people exercising program.
AB  - The objective of this longitudinal study was to determine the feasibility of a
      model for disseminating community-based strength training programs for older
      adults through leadership training of laypersons or "peers" and health and
      fitness professionals. The intervention consisted of a progressive strength
      training, balance, and flexibility exercise program and a leader training and
      certification workshop. Feasibility was defined as 75% or more of individuals who
      completed leader training establishing or teaching at least two 12-week strength
      training classes within 1 year. Program dissemination was quantified as the
      number of classes established between January 2005 and December 2006. Demographic
      characteristics and health status of leaders and program participants were
      evaluated. Two hundred forty-four leaders (peers, n=149; professionals, n=95)
      were trained and certified. Seventy-nine percent of all leaders (n=193) met the
      feasibility criteria of establishing or teaching strength training classes. There
      was no difference in the percentage of peer leaders (80%, n=119) and professional
      leaders (78%, n=74) who established or taught classes (P5.71) despite significant
      differences in their demographic and health profiles. Ninety-seven self
      sustaining strength training classes were established in senior and community
      centers, and 2,217 older adults (women, n=1,942; men, n=275) aged 50 to 97 with
      multiple chronic medical conditions enrolled. In conclusion, training peer and
      professional leaders is a feasible and successful model for disseminating a
      community strength training program for older adults. Widespread dissemination of
      this program has significant public health implications for increasing physical
      activity participation by older adults.

PMID- 19112655
TI  - A response to Rhode: natural laws, vacant niches and superorganisms.

PMID- 19112656
TI  - Light regulation of Ca2+ in the cone photoreceptor synaptic  terminal.
AB  - Retinal cones are depolarized in darkness, keeping voltage-gated Ca2+ channels
      open and sustaining exocytosis of synaptic vesicles. Light hyperpolarizes the
      membrane potential, closing Ca2+ channels and suppressing exocytosis. Here, we
      quantify the Ca2+ concentration in cone terminals, with Ca2+ indicator dyes. Two
      photon ratiometric imaging of fura-2 shows that global Ca2+ averages
      approximately 360 nM in darkness and falls to approximately 190 nM in bright
      light. Depolarizing cones from their light to their dark membrane potential
      reveals hot spots of Ca2+ that co-label with a fluorescent probe for the synaptic
      ribbon protein ribeye, consistent with tight localization of Ca2+ channels near
      ribbons. Measurements with a low-affinity Ca2+ indicator show that the local Ca2+
      concentration near the ribbon exceeds 4 M in darkness. The high level of Ca2+
      near the ribbon combined with previous estimates of the Ca2+ sensitivity of
      release leads to a predicted dark release rate that is much faster than observed,
      suggesting that the cone synapse operates in a maintained state of synaptic
      depression in darkness.

PMID- 19112657
TI  - Expression of calcium-binding proteins in pathways from   the nucleus of the
      basal optic root to the cerebellum in pigeons.
AB  - Calcium-binding protein expression has proven useful in delineating neural
      pathways. For example, in birds, calbindin is strongly expressed in the
      tectofugal pathway, whereas parvalbumin (PV) is strongly expressed in the
      thalamofugal pathway. Whether neurons within other visual regions also
      differentially express calcium-binding proteins, however, has not been
      extensively studied. The nucleus of the basal optic root (nBOR) is a retinal
      recipient nucleus that is critical for the generation of the optokinetic
      response. The nBOR projects to the cerebellum both directly and indirectly via
      the inferior olive (IO). The cerebellar and IO projections originate from
      different neurons within the nBOR, but whether they can also be differentiated
      based on calcium-binding protein expression is unknown. In this study, we
      combined retrograde neuronal tracing from the cerebellum and IO with fluorescent
      immunohistochemistry for PV and calretinin (CR) in the nBOR of pigeons. We found
      that about half (52.3%) of the cerebellar-projecting neurons were CR+ve, and
      about one-third (33.6%) were PV+ve. Most (90%) of these PV+ve cells were also
      labeled for CR. In contrast, very few of the IO-projecting neurons expressed CR
      or PV (<or=2%). Thus, the direct nBOR-cerebellar and indirect nBOR
      olivocerebellar pathways to the cerebellum can be distinguished based on the
      differential expression of CR and PV.

PMID- 19112658
TI  - Environmental credit crunch.

PMID- 19112659
TI  - Nobel questions.

PMID- 19112660
TI  - Fish falls.

PMID- 19112661
TI  - Sex and the drought.

PMID- 19112662
TI  - Off peak.

PMID- 19112663
TI  - Joan E. Strassmann.

PMID- 19112666
TI  - [Pulmonary hemorrhages. Part 1. Etiology. Pathogenesis. Medical treatment.
      Collapse therapy. Endoscopic studies].

PMID- 19112667
TI  - [Interpretation of complex cohort assessment of the results of tuberculin
      diagnosis].
AB  - Tuberculin tests were assessed from the results of a planned Mantoux test with 2
      TE, which were presented in the annual reports over the past years (2000-2006 and
      2001-2006). Cohorts of children born in 1999 and 2000 who were in 2006, 7 and 6
      years, respectively, were formed. This made it possible to monitor the time
      course of changes in tuberculin tests, postvaccinal allergy (PVA), primary
      Mycobacterium tuberculosis infection (PMBTI) and MBT infection. A cohort study of
      the results of tuberculin diagnosis has indicated that annual underestimation of
      children with PVA results in an increase in the rates of PMBTI. The authors prove
      that the rates of PMBTI and MBT infections in children incur a large proportion
      of errors therefore they should be used in the assessment of the tuberculosis
      epidemic situation with great caution.

PMID- 19112665
TI  - Design and Applications of Bifunctional Small Molecules: Why Two Heads Are Better
      Than One.
AB  - Induction of protein--protein interactions is a daunting challenge, but recent
      studies show promise for small molecules that specifically bring two or more
      protein molecules together for enhanced or novel biological effect. The first
      such bifunctional molecules were the rapamycin- and FK506-based "chemical
      inducers of dimerization", but the field has since expanded with new molecules
      and new applications in chemical genetics and cell biology. Examples include
      coumermycin-mediated gyrase B dimerization, proteolysis targeting chimeric
      molecules (PROTACs), drug hybrids, and strategies for exploiting multivalency in
      toxin binding and antibody recruitment. This Review discusses these and other
      advances in the design and use of bifunctional small molecules and potential
      strategies for future systems.

PMID- 19112668
TI  - Re: Rix TE, Sinha P. Inadvertent parathyroid excision during thyroid surgery.
      Surgeon 2006; 4(6): 339-42.

PMID- 19112669
TI  - Re: Vishwanathan H et al. Superglue in otology. Surgeon 2007: 5: 10-12.

PMID- 19112670
TI  - Treating prostate cancer, Part IV: surgery.

PMID- 19112671
TI  - Heat wave.

PMID- 19112672
TI  - Rating America's hospitals.

PMID- 19112673
TI  - On call.  My wife doesn't want our son to go out for the wrestling team because
      she's worried he might catch herpes.  I thought herpes was contracted from a very
      different contact sport.  Please enlighten us.

PMID- 19112674
TI  - [It happened...].

PMID- 19112675
TI  - [Treatises on the art of clothing in modern Spain].

PMID- 19112676
TI  - Developmentalism and its environmental legacy: the western Australia wheatbelt,
      1900-1990s.

PMID- 19112677
TI  - Selective bibliography of Belgian historical demography, 1981-2001 (19th and
      early 20th centuries).

PMID- 19112679
TI  - Introduction.
AB  - The traditional approach to the diagnosis and management of chronic obstructive
      pulmonary disease (COPD), cardiovascular disease, and lung cancer has been to
      address each separately. Guidelines have documented the scientific basis for
      diagnosis and management, but have done little to explore the interconnections
      between them or to address comorbidity. The past few years have seen greater
      attention to the problem of chronic diseases and increased awareness of the
      impending crisis in health care as a result of the changing demographics of the
      world's population with a steady increase in life expectancy and a higher
      proportion living into the chronic disease age range. COPD presents a particular
      problem, as its mortality rate continues to climb steadily in most countries,
      particularly in women. The same is true for lung cancer. Cardiovascular disease
      mortality shows a different pattern, with deaths continuing to increase in
      developing countries but stabilizing or decreasing in resource-rich countries as
      aggressive strategies to diagnose and treat cardiovascular disease have been put
      into place. Predictions for 2020 from the Global Burden of Disease Study are that
      ischemic heart disease will stay the number one cause of death worldwide, COPD
      will go from sixth to third place, and lung cancer will go from tenth to fifth
      place. The purpose of this introduction is to set the stage for a review and
      discussion of the major comorbidities of COPD, heart disease, and lung cancer, to
      expand our understanding of the interrelationships among the "Big Three"
      diseases, causes of morbidity and mortality worldwide.

PMID- 19112678
TI  - Working-class girls: the life-courses of 33 women cotton workers in Ghent around
      1900.

PMID- 19112680
TI  - The decline of infant mortality in the Belgian districts at the turn of the 20th
      century.

PMID- 19112681
TI  - The church and the family in Belgium, 1850-1914.

PMID- 19112682
TI  - Toll-free number for reporting adverse events on labeling for human drug
      products. Final rule.
AB  - The Food and Drug Administration (FDA) is issuing a final rule that confirms the
      interim final rule entitled "Toll-Free Number for Reporting Adverse Events on
      Labeling for Human Drug Products" (73 FR 402, January 3, 2008) (interim final
      rule) and responds to comments submitted in response to the request for comments
      in the proposed rule of the same title (69 FR 21778, April 22, 2004) (proposed
      rule). This final rule affirms the interim final rule's requirement for the
      addition of a statement to the labeling for certain human drug products for which
      an application is approved under section 505 of the Federal Food, Drug, and
      Cosmetic Act (the act). The statement includes a toll-free number and advises
      that the number is to be used only for reporting side effects and is not intended
      for medical advice (the side effects statement). This final rule also affirms the
      interim final rule's addition of new part 209 to the regulations requiring
      distribution of the side effects statement. This final rule implements provisions
      of the Best Pharmaceuticals for Children Act (the BPCA) and the Food and Drug
      Administration Amendments Act of 2007 (FDAAA).

PMID- 19112687
TI  - Oculofacial plastic and reconstructive surgery.

PMID- 19112683
TI  - The fertility decline in the industrial area of Charleroi during the second half
      of the 19th century: did sedentaries and migrants have a different behaviour?

PMID- 19112690
TI  - Economic analysis of HIV prevention interventions  in Andhra Pradesh state of
      India to inform  resource allocation.
AB  - OBJECTIVE: To conduct composite economic analysis of HIV prevention interventions
      to inform efficient utilization of resources in India. METHODS: We obtained
      output and economic cost data for the 2005-2006 fiscal year from a representative
      sample of 128 public-funded HIV prevention programmes of 14 types in Andhra
      Pradesh state of India. Using data from various sources, we developed a model to
      estimate the number of HIV infections averted. We estimated the additional HIV
      infections that could be averted if each intervention reached optimal coverage
      and the associated cost. RESULTS: In a year, 9688 HIV infections were averted by
      public-funded HIV prevention interventions in Andhra Pradesh. Scaling-up
      interventions to the optimal level would require US$38.8 million annually, 2.8
      times the US$13.8 million economic cost in 2005-2006. This could increase the
      number of HIV infections averted by 2.4-fold, if with higher resources there were
      many-fold increases in the proportional allocation for programmes for migrant
      labourers, men who have sex with men and voluntary counselling and testing, and
      reduction of the high proportion for mass media campaigns to one-third of the
      2005-2006 proportion of resource utilization. If the proportions of resource
      allocation for interventions remained similar to 2005-2006, the higher resources
      would avert 54% of the additional avertable HIV infections. CONCLUSION: The
      recent four-fold increase in public funding for HIV/AIDS control in India should
      be adequate to scale-up HIV prevention interventions to an optimal level in
      Andhra Pradesh, but the prevention would be suboptimal if additional investments
      were not preferentially directed to some particular interventions.

PMID- 19112691
TI  - Evaluation of the anti-HIV activity of natalizumab,  an antibody against integrin
      alpha4.
AB  - The alpha4beta7 integrin has been shown to serve as a coreceptor for HIV. One
      anti-alpha4 integrin agent (natalizumab) has been approved for the treatment of
      multiple sclerosis and Crohn's disease. We found that activation of CD4+ T cells
      with retinoic acid induced the upregulation of alpha4 and beta7 integrins.
      However, natalizumab failed to block the replication of HIV-1 strains in lymphoid
      MT-4 cells or CD4+ T cells at concentrations up to 125microg/ml. Our results
      suggest that alpha4 integrins are not essential cofactors for HIV replication.

PMID- 19112692
TI  - Alan Lyell MD (Cantab), FRCP (Ed), FRCP (Glas) 4th November 1917-2nd November
      2007.

PMID- 19112693
TI  - [Public relief for the elderly in 19th-century Antwerp].

PMID- 19112694
TI  - [Marriage during Lent and Advent in 19th-century Flanders].

PMID- 19112695
TI  - Yale Journal of Biology and Medicine. Introduction.

PMID- 19112696
TI  - Malthusian sinners: illegitimate fertility and economic crisis: a case study in
      Leuven, 1846-1856.

PMID- 19112697
TI  - [Youth, movement, and regeneration: an introduction].

PMID- 19112698
TI  - [Measure and reconciliation: Louis Vervaeck and Belgian criminal anthropology,
      ca. 1900-40].

PMID- 19112700
TI  - Medicaid program; clarification of outpatient hospital facility (including
      outpatient hospital clinic) services definition. Final rule.
AB  - Outpatient hospital services are a mandatory part of the standard Medicaid
      benefit package. This final rule aligns the Medicaid definition of outpatient
      hospital services more closely to the Medicare definition in order to: Improve
      the functionality of the applicable upper payment limits (which are based on a
      comparison to Medicare payments for the same services), provide more transparency
      in determining available hospital coverage in any State, and generally clarify
      the scope of services for which Federal financial participation (FFP) is
      available under the outpatient hospital services benefit category.

PMID- 19112699
TI  - [Indecent behavior of young women and generational conflicts: parental complaints
      about unruly daughters to the juvenile court of Antwerp, 1912-13 and 1924-25].

PMID- 19112701
TI  - Prior notice of imported food under the Public Health Security and Bioterrorism
      Preparedness and Response Act of 2002. Final rule.
AB  - The Food and Drug Administration (FDA) is issuing a final regulation that
      requires the submission to FDA of prior notice of food, including animal feed,
      that is imported or offered for import into the United States. The final rule
      implements the Public Health Security and Bioterrorism Preparedness and Response
      Act of 2002 (the Bioterrorism Act), which required prior notification of imported
      food to begin on December 12, 2003. The final rule requires that the prior notice
      be submitted to FDA electronically via either the U.S. Customs and Border
      Protection (CBP or Customs) Automated Broker Interface (ABI) of the Automated
      Commercial System (ACS) or the FDA Prior Notice System Interface (FDA PNSI). The
      information must be submitted and confirmed electronically as facially complete
      by FDA for review no less than 8 hours (for food arriving by water), 4 hours (for
      food arriving by air or land/rail), and 2 hours (for food arriving by land/road)
      before the food arrives at the port of arrival. Food imported or offered for
      import without adequate prior notice is subject to refusal and, if refused, must
      be held. Elsewhere in this issue of the Federal Register, FDA is announcing the
      availability of a draft compliance policy guide (CPG) entitled "Sec. 110.310
      Prior Notice of Imported Food Under the Public Health Security and Bioterrorism
      Preparedness and Response Act of 2002."

PMID- 19112702
TI  - Representative payment under titles II, VIII and XVI of the Social Security Act.
      Final rule.
AB  - We are amending our rules governing how we investigate representative payee
      applicants. Under these rules, any payee who previously satisfied the payee
      investigation criteria, including a face-to-face interview, and currently serves
      as a payee generally need not appear for another face-to-face interview when
      subsequently applying to become a payee unless we determine within our
      discretion, that a new face-to-face interview is necessary. The payee applicant
      would still be required to satisfy the rest of the investigation process as set
      forth in the regulations. Reducing the number of subsequent face-to-face
      interviews of payee applicants will streamline our representative payee
      application process, allowing payee applicants to become qualified more quickly
      when they already serve as a payee. This rule also will expedite payment of
      benefits in certain representative payee situations and reduce the burden on our
      field office employees by eliminating the necessity of interviewing such payee
      applicants.

PMID- 19112703
TI  - Obstetrical and gynecological devices; designation of special controls for male
      condoms made of natural rubber latex.
AB  - The Food and Drug Administration (FDA) is amending the classification regulation
      for condoms to designate a special control for male condoms made of natural
      rubber latex (latex). The special control for the device is the guidance document
      entitled "Class II Special Controls Guidance Document: Labeling for Natural
      Rubber Latex Condoms Classified Under 21 CFR 884.5300." The FDA will publish a
      notice in the Federal Register announcing the availability of the special control
      guidance document no later than the effective date of this final rule.

PMID- 19112704
TI  - Schedule for rating disabilities; eye. Final rule.
AB  - This document amends the Department of Veterans Affairs (VA) Schedule for Rating
      Disabilities (Rating Schedule) by updating the portion of the schedule that
      addresses disabilities of the eye. These amendments ensure that the schedule uses
      current medical terminology, provides unambiguous criteria for evaluating
      disabilities, and incorporates pertinent medical advances.

PMID- 19112705
TI  - African jubilee: Mau Mau resurgence and the fight for fertility in Kenya, 1986
      2002.

PMID- 19112706
TI  - Fifteen years of the Chernobyl catastrophe.

PMID- 19112707
TI  - Lives of the saints: international hardship duty in Chad.

PMID- 19112708
TI  - Doing it: a new edition of The joy of sex.

PMID- 19112709
TI  - Mammalian isovalthine metabolism.
AB  - Isovalthine is a branched-chain sulphur amino acid, which has been found in the
      urine of normal cats. The concentrations of isovalthine in the urine of healthy
      adult cats are approximately 24-66 micromol/l and are not affected by the gender
      of the cat. Isovalthinuria can be induced in other species (rats, rabbits, guinea
      pigs, humans, dogs) following the administration of certain inducing agents such
      as some hypocholesterolaemic agents, bile acids, hormones or cholesterol
      precursors. The method of induction of isovalthinuria was studied extensively
      during the 1960s, and efforts were made to understand its biosynthesis. However,
      although the origin of the sulphur atom in isovalthine was shown to be from
      cysteine or methionine, the origin of the carbon skeleton remains unknown.
      Interest in isovalthine metabolism was generated in part because it was
      reportedly found in the urine of patients with hypercholesterolaemia. The
      validity of this finding however, was brought into question following reports
      that administration of the drug Bromural (alpha-bromoisovalerylurea), to humans
      results in the generation of compounds which break down to yield isovalthine
      following acid hydrolysis. This article presents a review and discussion of the
      experimental data on isovalthine metabolism.

PMID- 19112710
TI  - Influence of crop residue ration supplementation on the attainment of puberty and
      postpartum reproductive activities of Red Sokoto goats.
AB  - The general objective of this study was to come up with an appropriate,
      affordable and locally available crop residue supplementation package that would
      enhance reproductive performance in small ruminants. Specifically, 28 Red Sokoto
      weaner does between 3 and 4 months of age weighing between 2 and 3 kg were used
      in the first experiment to determine the influence of crop residue
      supplementation on age and weight at puberty as determined by blood progesterone
      levels. In the second experiment, another 28 adult does (> or = 2 years old) of
      the same breed in the same flock with lactation numbers between 1 and 3 were used
      to determine the length of postpartum acyclic period. In both experiments, a 3 x
      2 factorial experimental design comprising three dietary supplements (A, B, C) at
      two feeding levels (1% and 2% of body weight) fed in addition to a basal diet of
      Digitaria smutsii hay and natural pasture ad libitum with an unsupplemented
      negative control group (D) and four goats per treatment was utilized. In ration
      A, a conventional concentrate supplement consisting of maize, wheat offal,
      cottonseed cake and bonemeal was utilized; in rations B and C, the supplement
      consisted of guinea-corn bran, cowpea husk and groundnut haulms; and maize offal,
      groundnut shells and groundnut haulms respectively. Unsupplemented (ration D)
      weaner does reached puberty at a later age and had lighter body weights than all
      the others. Weaner does on ration 2A (concentrate fed at 2% of body weight)
      attained puberty at the earliest age and heaviest body weight, although the age
      at puberty was not significantly different from those on rations 1A (concentrate
      fed at 1% body weight), 1C and 2C. Blood progesterone profiles before and after
      puberty ranged from 0.05 to 9.0 ng/ml, respectively, and was highest in does fed
      rations A and C and least in the unsupplemented does. The mean interval between
      kidding and initiation of ovarian activity was 54.28 +/- 17.61 days and the mean
      interval between kidding and conception was 63.04 +/- 25.34 days. Only 25% of the
      unsupplemented does conceived again during the period under study compared with
      100% in rations 1A, 2A, 1C and 2C; 75% in ration 2B and 50% in ration 1B. It was
      concluded that implementation of supplementary feeding in the dry season improves
      reproductive performance in the Red Sokoto doe. Furthermore, ration C, a crop
      residue-based ration, was a suitable dry season supplementation alternative to
      the expensive conventional concentrate ration for the smallholder goat farmer in
      the subhumid tropics of Nigeria.

PMID- 19112711
TI  - Effect of dietary vitamin E and partial replacement of poly- with monounsaturated
      fat on fatty acid patterns of backfat and intramuscular fat in heavy pigs
      (Iberian x Duroc).
AB  - The effects of partial replacement of dietary polyunsaturated fatty acid (PUFA)
      with monounsaturated fatty acid (MUFA) on fatty acid profiles of subcutaneous and
      intramuscular fat and rheological properties of fat were studied in heavy pigs.
      No effect of dietary fat was observed on total saturated fatty acids proportion
      in outer and inner backfat layers or intramuscular neutral and polar lipids. The
      partial substitution of dietary PUFA by MUFA produced a rise in MUFA of
      intramuscular polar lipids (p < 0.01) but neutral lipids were not affected.
      Moreover, it also decreased (p < 0.01) the n-6 proportion of outer and inner
      backfat layers and intramuscular polar lipids, but no effect was observed for the
      n-6 in the intramuscular neutral lipids. No significant effect of dietary fat
      treatment was observed on n-3 fatty acids in outer and inner backfat layers, but
      the partial substitution of PUFA by MUFA increased (p < 0.01) the n-3 proportion
      of intramuscular lipid fractions and the consequent decreased in the n-6/n-3
      ratio in all lipid location. Significant effects of dietary vitamin E were
      observed on springiness, cohesiveness and adhesiveness of backfat inner layer.
      However, consistency was not affected by dietary fat. Further research is needed
      to establish the effects of different ranges of dietary oil combination in the
      feeding of heavy pigs.

PMID- 19112712
TI  - Growth performance and body composition of goat kids fed milk replacers with
      increasing levels of linoleic acid.
AB  - Twenty, 1-2-day-old goat kids were used in a feeding trial to investigate the
      effect of linoleic acid (LA) (C18:2n-6) intake on weight gain and carcass
      composition. Eight animals were selected randomly and killed at the start of the
      trial to determine initial body composition. The other animals were assigned to
      the three dietary treatments and were fed milk replacers with varying LA
      concentrations (low: 5.5%; medium: 11.2% and high: 17.1% LA of total fatty acids)
      for 5 weeks. There was no systematic effect of LA intake on body composition. The
      average retentions of fat, protein, ash and energy were 46.3%, 61.2%, 42.2% and
      37.4% respectively. Increased intakes of LA caused a significant increase in LA
      content of the carcass and of the weight gain, whereas there was a simultaneous
      decrease in fatty acids with 16 carbon atoms or less. The incorporation of LA
      into carcass was directly related to intake, but the percentage retention of LA
      remained constant. The data indicate that in goat kids the intake of extra LA
      raises the amount of LA in carcass but does not affect the total fat content.

PMID- 19112713
TI  - Ascorbic acid concentrations in milk from Sudanese camels.
AB  - The present study in Sudanese camels was done to describe the associations
      between vitamin C concentrations in milk, and either breed, stage of lactation,
      parity or the presence of mastitis. A total of 2586 camels were sampled. Arabi
      camels had higher ascorbic acid levels in milk than did either Anafi or Bishari
      camels. Milk ascorbic acid levels were higher for camels more than 180 days in
      lactation than for those earlier in lactation. Multiparous vs. primiparous camels
      had higher ascorbic acid concentrations in their milk. The ascorbic acid content
      of colostrum was higher than that of milk. Mastitis was associated with a
      decrease in the ascorbic acid content of both milk and blood plasma.

PMID- 19112714
TI  - Nitric oxide influences the meiotic maturation of porcine oocytes cultured in
      hypoxanthine-supplemented medium.
AB  - Nitric oxide (NO) plays an important role in many pathological processes. The
      present investigation was undertaken to ascertain the effects of NO at high level
      on porcine oocyte meiotic development. Cumulus-enclosed oocytes (CEOs) and
      denuded oocytes (DOs) were obtained from the follicles (2-6 mm diameter).
      Exogenous NO was provided with sodium nitroprusside (SNP). Control (0 mM), 0.1
      mM, 1 mM or 10 mM SNP was introduced to the medium. Meanwhile, 0.1 mM, 1 mM and
      10 mM preincubated SNP was also added to the medium respectively. The cumulus
      expansion, cumulus cells DNA fragmentation, oocyte meiotic maturation and
      degeneration were determined 44 h after incubation. SNP inhibited cumulus
      expansion and cumulus cells DNA fragmentation in a dose-dependent manner.
      Significantly fewer CEOs treated by any level of SNP resumed meiosis than control
      (p < 0.05) and more CEOs exposed to 0.1 mM or 1 mM SNP were arrested at GV stage.
      Moreover, SNP increased the percentage of CEOs at metaphase I (MI) stage but
      decreased the percentage of CEOs at metaphase II (MII) stage. 0.1 mM or 1 mM SNP
      showed no influence on the proportion of germinal vesicle breakdown of DOs and
      only 10 mM SNP reduced the proportion. SNP accelerated degeneration of both CEOs
      and DOs, especially at higher concentrations. DOs were more sensitive to SNP
      toxicity. Preincubated SNP showed no effect on cumulus expansion, cumulus cells
      DNA fragmentation, oocyte meiotic maturation or degeneration at lower
      concentration, but higher concentrations had effect, especially on the viability
      of porcine oocytes. Taken together, high level of NO inhibits porcine oocyte
      meiotic maturation, especially the transition from MI to MII, by mediating the
      functions of cumulus cells.

PMID- 19112715
TI  - Effect of linseed oil supplementation on concentrations of (n-3) polyunsaturated
      fatty acids in liver phospholipids of rats fed diets containing either an oil
      rich in conjugated linoleic acids, sunflower oil or high-oleic acid sunflower
      oil.
AB  - This study investigated the metabolism of alpha-linolenic acid and the formation
      of eicosanoids in rats fed diets with three different dietary fats (30 g/kg
      diet): either a conjugated linoleic acid (CLA) preparation with a high
      concentration of cis-9, trans-11 CLA (32.2 g/100 g) and trans-10, cis-12 CLA
      (33.3 g/100 g) and a low concentration of linoleic acid (0.5 g/100 g), sunflower
      oil (SFO) with a high concentration of linoleic acid or high-oleic acid sunflower
      oil (HO-SFO) with a high concentration of oleic acid. Basal diets with those oils
      were fed for 4 weeks. In the fifth week, the same diets supplemented with 50 g of
      linseed oil/kg as a source of alpha-linolenic acid were fed. To study the effect
      of the oils on the metabolism of alpha-linolenic acid, the amounts of individual
      (n-3) polyunsaturated fatty acids (PUFA) in liver phospholipids (phosphatidyl
      choline and phosphatidyl ethanolamine) were determined; to study the effect on
      eicosanoid formation, the concentrations of various two-series eicosanoids in
      liver and plasma, the activity of the secretory phospholipase A2 and the relative
      mRNA concentrations of cyclooxygenases-1 and 2 in the liver were measured. Rats
      fed the CLA diets had the highest concentrations of long chain (n-3) PUFA
      deriving from delta6, delta5 and 14-desaturation of alpha-linolenic acid in liver
      phospholipids; rats fed the SFO diet had the lowest concentrations of those fatty
      acids. The concentration of arachidonic acid in liver phospholipids and the
      concentrations of eicosanoids in liver and plasma were lowest in rats fed the CLA
      diet and highest in the rats fed the SFO diet. Moreover, rats fed the CLA diet
      had a higher gene expression of delta6-desaturase in the liver than the other two
      groups of rats. The results show that feeding the CLA oil reduced the formation
      of arachidonic acid and eicosanoids but enhanced the formation of long chain (n
      3) PUFA and their incorporation into tissue lipids when compared with feeding SFO
      or HO-SFO.

PMID- 19112716
TI  - Variation of plasma parameters and nitrogen metabolism in finishing Belgian blue
      double-muscled cull females.
AB  - The changes over time in plasma parameters and nitrogen metabolism were studied
      in finishing Belgian Blue double-muscled females offered a maize silage based
      diet. When compared with literature data, plasma glucose along with triglycerides
      concentrations was low while non-esterifled fatty acids were high and rich in
      polyunsaturated forms. The concentrations in thyroid hormones, insulin-like
      growth factor 1 and insulin were also low and plasma insulin decreased with time.
      Growth hormone concentration, by contrast, increased with time. On average, the
      females retained 44 g nitrogen per day from an intake of 210 g but the efficiency
      of retention decreased with time. The fractional rates of accretion and synthesis
      of muscle protein were also affected by time. The dry matter content in muscle
      biopsies was close to 22% and increased with the finishing, as did the diameter
      of the tailhead adipocytes.

PMID- 19112717
TI  - [The teaching of pharmacology in medical schools: current status and future
      perspectives].
AB  - Pharmacology is a core course in all medical school curricula. In most medical
      schools, pharmacology is taught during the second year and teaching covers both
      basic aspects and useful drugs for the treatment of human diseases. It is assumed
      that relevant pharmacologic knowledge is revisited during the clinical clerkships
      and that students are adequately trained to prescribe drugs upon graduation.
      However, for many years it has been noted that pharmacological training is
      sometimes insufficient and that inadequate and irrational prescription of drugs
      is a very common problem in clinical settings. Information overload and
      proliferation of new drugs have been recognized as two of the major contributing
      factors. To address this issue, many authors have recommended the development of
      a core curricula in pharmacology which all students would have to complete
      coupled with a restricted list of drugs. Based on our own teaching experience we
      have identified what should constitute the core content of pharmacology courses
      in medical schools and have written a study guide for this discipline. Both
      documents provide an organizational framework to help second year medical
      students ascertain what part of the vast knowledge in pharmacology they need to
      learn. The number of drugs that students have to manage is limited to 168. Our
      program constitutes the first effort to medicalize the teaching of pharmacology
      in medical schools. We expect that most medical schools will follow our
      guidelines as our program is applicable to all curricula modalities.

PMID- 19112718
TI  - [Transciptome among Mexicans: a large scale methodology to analyze the genetics
      expression profile of simultaneous samples in muscle, adipose tissue and
      lymphocytes obtained from the same individual].
AB  - OBJECTIVE: We describe the methodology used to analyze multiple transcripts using
      microarray techniques in simultaneous biopsies of muscle, adipose tissue and
      lymphocytes obtained from the same individual as part of the standard protocol of
      the Genetics of Metabolic Diseases in Mexico: GEMM Family Study. METHODS: We
      recruited 4 healthy male subjects with BM1 20-41, who signed an informed consent
      letter. Subjects participated in a clinical examination that included
      anthropometric and body composition measurements, muscle biopsies (vastus
      lateralis) subcutaneous fat biopsies anda blood draw. All samples provided
      sufficient amplified RNA for microarray analysis. Total RNA was extracted from
      the biopsy samples and amplified for analysis. RESULTS: Of the 48,687 transcript
      targets queried, 39.4% were detectable in a least one of the studied tissues.
      Leptin was not detectable in lymphocytes, weakly expressed in muscle, but
      overexpressed and highly correlated with BMI in subcutaneous fat. Another example
      was GLUT4, which was detectable only in muscle and not correlated with BMI.
      Expression level concordance was 0.7 (p< 0.001) for the three tissues studied.
      CONCLUSIONS: We demonstrated the feasibility of carrying out simultaneous
      analysis of gene expression in multiple tissues, concordance of genetic
      expression in different tissues, and obtained confidence that this method
      corroborates the expected biological relationships among LEPand GLUT4. TheGEMM
      study will provide a broad and valuable overview on metabolic diseases, including
      obesity and type 2 diabetes.

PMID- 19112719
TI  - [Seroreactivity to hepatitis B virus surface antigen among different population
      groups in the City of Durango, Mexico].
AB  - OBJECTIVE: To determine the seroprevalence of hepatitis B surface antigen (HBsAg)
      in several groups of populations in Durango City, Mexico. METHODS: An
      observational and comparative study was conducted in 6 groups of population in a
      total of 775 persons in Durango City, Mexico. The groups studied were 141
      registered female sex workers, 100 medical students, 150 blood donors, 104
      persons applying for medical certificates, 100 pregnant women, and 180 drug
      addicts. Serum samples of participants were analyzed for HBsAg by an immunoassay.
      HBsAg confirmation was performed by neutralization assay. RESULTS: Out of the 775
      participants, 13 (1.7%) were positive by the immunoassay, and only 1 (0.1%)
      resulted positive by the confirmatory assay. This positive case was a drug addict
      and had a history of surgery and national and international trips. CONCLUSIONS:
      The seroprevalence of HBsAg in several groups of population in Durango City is
      low; the seroprevalence is comparable to or lower than those informed in other
      Mexican cities. It is strongly recommended to perform the HBsAg confirmation test
      due to low specificity of the immunoassay.

PMID- 19112720
TI  - [Adolescents with de novo acute lymphoblastic leukemia: efficacy and safety of a
      pediatric vs adult treatment protocol].
AB  - OBJECTIVE: To ascertain the efficacy and safety of two chemotherapy regimens, one
      designed for adults and the other for children, in adolescent patients with acute
      lymphoblastic leukemia (ALL). METHODS: Between 2001-2006, we included patients
      aged 15-25, with de novo, Phi(-) ALL, without initial central nervous system
      (CNS) infiltration. Twenty patients received a chemotherapy regimen designed for
      children with high-risk ALL (LALIN) and twenty a regimen for adults (LALA). Both
      were intensive and included dexamethasone, daunorubicin, cyclophosphamide,
      vincristine, cytarabine, methotrexate and mercaptopurine as well as CNS
      prophylaxis. Elective suspension of chemotherapy occurred at two and three years
      respectively, in patients with continued complete remission. RESULTS: Patients in
      both groups were comparable in age, sex, presence and size of hepatosplenomegaly,
      initial leukocytes and platelet counts. Predominant in both groups was L2
      morphology and B-cell CD10(+) immunophenotype. Results for the LALIN/ LALA groups
      were: failures 2/0 (p=0.49); relapses 0/4 (p= 0.05); therapy associated deaths
      4/7 (p= 0.48); and event free survival at 70 months follow-up was 70% and 40%
      (p=0.12). CONCLUSIONS: In patients aged 15-25, with de novo ALL, a chemotherapy
      regimen designed for children had significantly less relapses than a regimen for
      adults. We saw no increase in toxicity in the LALIN versus the LALA group.

PMID- 19112721
TI  - [Reliability and factorial analysis of the Spanish version of the Pittsburg Sleep
      Quality Index among psychiatric patients].
AB  - INTRODUCTION: The Pittsburgh Sleep Quality Index (PSQI) has become a standard
      instrument to measure sleep quality. However, its factor structure has not been
      fully explored and the available Spanish versions have revealed the need to make
      adaptations. Our objective was to assess the factor structure and reliability of
      the PSQI. METHODS: Eighty seven psychiatric patients without treatment and 48
      control subjects underwent psychiatric structured assessment and completed the
      PSQI. Internal consistency and factor structure of PSQI was measured and the
      scale scores were compared between groups and by gender. Association with age was
      also calculated. RESULTS: There were no significant differences between
      psychiatric patients and control subjects on age and gender. Subjects had no
      problem understanding and answering the questions in the instrument. The PSQI
      displayed a satisfactory reliability coefficient (0.78) and component-total score
      correlations were all significant (0.53-0.77). The PSQI showed two main factors:
      sleep duration and sleep quality. Patients obtained significantly higher scores
      than controls, in both the global and the component scores, with the exception of
      sleep duration. The PSQI scores were not significantly different between males
      and females and were not associated with age. CONCLUSIONS: The PSQI is a reliable
      instrument to measure sleep quality in Mexican subjects.

PMID- 19112722
TI  - [The effect of ibuprofen and acetylsalicylic acid on cognitive impairment, total
      antioxidant power and isoprostane serum].
AB  - INTRODUCTION: There are controversial studies on the prevention of Alzheimer's
      disease with nonsteroidal antiinflammatory drugs (NSAIDs). The objective of this
      study was to evaluate the effect of ibuprofen and acetylsalicylic acid on
      cognitive impairment, serum total antioxidant power (TAP) and isoprostane (8-iso
      PGF2alpha). METHODS: From April 2004 to February 2006, a Folstein mini-mental
      state (MMSE), Syndrome Kurtz Test (SKT) and a geriatric depression scale
      (Yasevage) were applied to eighteen, 55-56 years old eligible women. All women
      (n= 18) with normal cognitive state were randomized to ibuprofen 400 mg per day
      (n= 9) and acetylsalicylic acid 500 mg per day (n= 9) for one year. Serum TAP and
      8-iso-PGF2alpha were performed at baseline, after six months and one year of
      treatment. RESULTS: After one year of treatment with acetylsalicylic acid five
      women (55.6%) raised their score 4 points in MMSE compared with 3 points
      increased (33.3%) showed by the ibuprofen group. TAP increased (p=0.01) and 8-iso
      PGF2alpha reduced (p=0.01) in both groups compared with baseline. CONCLUSIONS:
      Both drugs improved the cognitive state andoxidative status of our population.

PMID- 19112724
TI  - [Therapeutic advances in nephrology].

PMID- 19112723
TI  - [Comparison of metoprolol vs clonazepam as a first treatment choice among
      patients with neurocardiogenic syncope].
AB  - OBJECTIVE: We compared the effects of a metoprolol and clonazepam in patients
      with neurocardiogenic syncope. METHODS: We compared the effects of a metoprolol
      and clonazepam in a prospective, randomised trial in 54 patients. Patients were
      randomly assigned to metoprolol (starting dose 50 mg bid) or clonazepam (starting
      dose 0.5 mg qd). We assessed a primary combined endpoint of syncope and pre
      syncope on a follow-up of 12 months. RESULTS: The primary combined endpoint of
      syncope and presyncope occurred in the metoprolol group in 3, 4, and 10% of
      patients at 3, 6, and 12 months respectively. In the clonazepam group it was no
      recurrence in the first 6 months, and 5% recurrence at 12 months follow-up
      (nonsignificant differences between groups). Clinical symptoms commonly
      associated with neurally mediated syncope were decreased similarly in both
      treatment groups, in the metoprolol group from 5.2+/-2.5 to 1.9+/-2.1 (p < 0.001)
      and in the clonazepam group from 5.5+/-2.5 to 1.5+/-2.2 (p<0.001). CONCLUSIONS:
      Pharmacological treatment of neurocardiogenic syncope with metoprolol or
      clonazepam resulted in similar prevention of syncope and presyncope. Both
      treatments decreased clinical symptoms but complete symptomatic resolution was
      rarely observed.

PMID- 19112725
TI  - [Is it possible to improve the death registries in Mexico?].
AB  - Regarding death registries, Mexico has more than one hundred years of experience.
      However, to date we have been unable to solve the problem of filling out
      correctly infant and maternal death certificates. The need to have a
      comprehensive death registry system as described in the Millennium Development
      Goals (MDGs) led the Health Information Office at the Ministry of Health, in
      2002, to initiate an "intentional search of maternal and infant deaths" at the
      national level in order to decrease the problems associated with
      misclassification of deaths. According to the estimates put forth by
      international agencies that do follow-up on the MDGs, after four years of work,
      this study reports a 20% improvement in the number of infant deaths registered
      and 36% of maternal deaths. The advances achieved through the intentional search
      allowed us to conclude than at least a significant aspect related to the
      improvement of death registries was completed. But we still have an important
      task before us. Fortunately, as a consequence of this study, next steps have been
      clearly defined and improvements will be achieved in the short term.

PMID- 19112727
TI  - [A fifty nine year old female presenting with nausea, vomiting and gait
      disorder].

PMID- 19112726
TI  - [Leptin and its association with obesity and type 2 diabetes].
AB  - The number of patients with metabolic disorders, obesity, type 2 diabetes and
      hypertension is increasing worldwide. The increase in body weight as a
      consequence of genetic, environmental, and nutritional factors contributes to
      these disorders, playing a significant role in their disease course. In 1994 the
      obesity gene (ob) which encodes a protein named leptin, considered an important
      molecule in regulation of body weight, was described Body weight gain has been
      generally correlated with high plasma levels of leptin, generating a state of
      leptin-resistance. Because of its association with obesity, leptin has also been
      connected with type 2 diabetes and insulin-resistance, an essential
      characteristic of this disease. Leptin has also been linked with other disorders
      such as dyslipidaemia, and cardiovascular disease (conditions that together are
      known as metabolic syndrome), as well as cancer, psychological deficits, sexual
      dysfunction, etc. We describe some important biochemical and molecular aspects
      associated with the physiology of leptin, emphasizing the pathological
      consequences associated with obesity and diabetes.

PMID- 19112728
TI  - [Genomics and schizophrenia].

PMID- 19112729
TI  - [A country doctor: a proposal of an ethical approach in the 125th anniversary of
      Frank Kafka's birth].
AB  - Within the framework of the 125 anniversary of the birth of Franz Kafka we
      discuss his work as a patient affected by tuberculosis. This essay outlines a
      review of Kafka as a writer and explains the meaning of the term "Kafkaesque". We
      put forward a commentary on the ethics expressed in a short story entitled A
      country doctor. An interpretation of Kafka must involve the notion of
      responsibility, a theological concept that is then followed by the legal context.
      Finally, Kafka embraces an ethical approach expressed in his work.

PMID- 19112730
TI  - Progress in the treatment of myelodysplastic syndromes.

PMID- 19112731
TI  - A rewarding fresh look at routine blood group data.

PMID- 19112732
TI  - Regulatory requirements and standards on clinical appropriateness of blood
      component transfusion.

PMID- 19112733
TI  - Clinical appropriateness of blood component transfusion: regulatory requirements
      and standards set by the Scientific Society in Italy.

PMID- 19112734
TI  - New drugs in the treatment of myelodysplastic syndromes: are they changing the
      role of transfusion support?

PMID- 19112736
TI  - Audit of the clinical use of fresh-frozen plasma in Umbria: study design and
      results of the pilot phase.
AB  - BACKGROUND: Fresh-frozen plasma (FFP) is unanimously recognised by international
      guidelines as the blood component of choice for the management of acute
      haemorrhage when accompanied by disorders of haemostasis, for disseminated
      intravascular coagulation in the presence of haemorrhage, for rare bleeding
      disorders when specific clotting factor concentrates are not available and for
      thrombotic thrombocytopenic purpura. The literature, however, reports a high
      percentage of inappropriate requests for FFP. This article presents the results
      of a pilot study of clinical auditing of the use of FFP in the Region of Umbria
      (Italy). METHODS: This study was based on the examination of the requests for FFP
      made in April 2006 to four Immunotransfusion Services (ITS) in Umbria and of the
      clinical records of the patients receiving transfusions. The following indicators
      were identified and evaluated: completeness of the request, appropriateness of
      the indication and the dose, completeness of the records in the clinical charts,
      adverse events, in-hospital morbidity and mortality, efficacy of the treatment
      (evaluated by analysing the changes between pre- and post-transfusion coagulation
      test results) and, as an indicator of the process, the correspondence between
      data in the paper request form and in the computerised database. The data were
      extracted from the ITS databases, from the paper request forms and from the
      patients' clinical records. RESULTS: Two hundred and twenty-one requests (615
      units of FFP) for 109 patients and 92.8% of the related clinical records were
      examined. The patients were admitted in medical (22.9%), surgical (51.4%) and
      critical care units (25.7%). In 50.7% of the cases, the completeness of the data
      in the individual requests was good (65-80% of the fields filled in). The
      indication was appropriate in 31.5% of the requests evaluated (56.1% of the
      total), with no difference related to different requesters. The dosage was
      appropriate in 62.7% of the requests evaluated (62% of the total). A comparison
      of pre- and posttransfusion laboratory data showed a significant correction of
      pathological values (p=0.02) only for the International Normalised Ratio (INR).
      CONCLUSIONS: Critical areas that should be targeted by interventions to improve
      plasma usage are those related to the appropriateness of the indication, the
      completeness of the data entered in the request forms and the data recorded in
      the clinical charts.

PMID- 19112735
TI  - The Chikungunya epidemic in Italy and its repercussion on the blood system.
AB  - BACKGROUND: The Chikungunya virus (CHIKV) is transmitted by Aedes mosquitoes and
      recently caused a massive epidemic on La Reunion Island, in the Indian Ocean.
      Between July and September 2007 it caused the first autochthonous epidemic
      outbreak in Europe, in the Region of Emilia-Romagna in the north-east of Italy.
      MATERIALS AND METHODS: After the first reports of an unusually high number of
      patients with a febrile illness of unknown origin in two contiguous villages, an
      outbreak investigation was carried out to identify the primary source of
      infection, the modes of transmission and the dynamics of the epidemic. An active
      surveillance system was also implemented. Laboratory diagnosis was performed
      through serology and polymerase chain reaction (PCR) analysis. Blood donation was
      discontinued in the areas involved from September to October 2007 and specific
      precautionary blood safety and self-sufficiency measures were adopted by the
      regional health and blood authorities and the National Blood Centre. An estimate
      method to early assess the risk of viraemic blood donations by asymptomatic
      donors was developed, as a tool for "pragmatic" risk assessment and management,
      aiming at providing a reliable order of magnitude of the mean risk of CHIKV
      transmission through blood transfusion. RESULTS: Two hundred and seventeen cases
      of CHIKV infection were identified between 4th July and 28th September. The
      disease was fairly mild in most of the cases. The precautionary measures adopted
      in the blood system caused a considerable reduction of the collection of blood
      components and of the delivery of plasma to the pharmaceutical industry for
      contract manufacturing. The estimated risk of CHIKV transmission through blood
      transfusion peaked in the third week of August. CONCLUSION: ACHIKV epidemic poses
      considerable problems for public health authorities, who not only need good
      routine programmes of vector control and epidemiological surveillance but also
      local and national emergency plans to sustain the blood supply, so as to promptly
      deal with the potentially severe effects of an epidemic outbreak, especially when
      affected areas locally require a significant blood inventory and at the same time
      represent a critical resource for other areas depending on external supplies of
      blood components.

PMID- 19112737
TI  - Peripheral blood CD5-positive B lymphocytes (B-1a cells) after allogeneic stem
      cell transplantation for acute myeloid leukaemia in humans.
AB  - BACKGROUND: Only few data are available in literature regarding the
      reconstitution of B- 1a cells after allogeneic bone marrow transplantation
      performed for haematological malignancies. METHODS: In this study we used flow
      cytometry to assess the reconstitution of the peripheral blood B-1a cell
      compartment after allogeneic peripheral blood stem cell transplantation.
      Cytometric analyses were performed over time on 11 consecutive patients
      undergoing allogeneic peripheral blood stem cell transplantation for acute
      myeloid leukaemia in our Haematology Unit and the results were compared with
      available data regarding B- 1a cell reconstitution after allogeneic bone marrow
      stem cell transplantation. RESULTS: In spite of an earlier recovery of B-1a cells
      in the peripheral blood after allogeneic bone marrow transplantation, the
      reconstitution of this B-cell subset was similar, regardless of the source of
      stem cells employed. CONCLUSIONS: Further studies are necessary in order to
      clarify the origin of B-1a cells in humans in health and illness.

PMID- 19112738
TI  - The persistence of red cell alloantibodies.
AB  - BACKGROUND: Red cell alloantibodies may disappear over time and cause a delayed
      haemolytic reaction if their past existence is not known before a transfusion.
      Only few quantitative data have already been presented on this topic. STUDY
      DESIGN AND METHODS: We retrieved the records of alloantibodies detected between
      1989 and 2008 in our institution. All warm-reacting alloantibodies were included,
      with the exception of ABO antibodies, anti-D in women of childbearing age (it was
      impossible to rule out Rh prophylaxis) and antibodies produced by transfusion
      dependent beta-thalassaemia patients (their transfusion history was too unusual).
      RESULTS: We found 673 antibodies, produced by 525 patients, which had been tested
      again after the initial detection. The median follow-up was 319 days. The overall
      rate of non-persistence was 37%, corresponding to 251 antibodies, produced by 216
      patients. Non-persistent antibodies were associated with a longer follow-up (409
      vs. 236 days; p=0.012), more tests after detection (2 vs. 1; p<0.001), and a
      lower maximum score (2+ vs. 3+; p<0.001). Antibody specificity, too, influenced
      the duration of persistence. Among common antibodies, anti-D was the most long
      lived (14% non-persistence); anti-Jka the most short-lived (43% non-persistence).
      Antibodies detected in the second decade of the study were less persistent
      (p<0.001). They were also weaker (maximum score: 2+ vs. 3+; p<0.001). This
      probably reflects the increased sensitivity of the screening tests over the
      course of time. Age, sex and whether the patient had produced multiple
      alloantibodies were not significant covariates. A minority of non-persistent
      antibodies (33/251, 13%) were detected again after a negative result
      (intermittently-detected antibodies). They had a longer follow-up (885 vs. 341
      days; p=0.002), more tests after detection (5 vs. 2; p<0.001), and a higher
      maximum score (3+ vs. 2+; p=0.001). CONCLUSIONS: Red cell antibodies commonly
      disappear. To avoid delayed haemolytic reactions, it is necessary to rely on
      previous records, which should be readily available.

PMID- 19112739
TI  - West Nile virus in Italy: a further threat to blood safety, a further challenge
      to the blood system.

PMID- 19112740
TI  - A comment on blood transfusion practice resulting from the data on the prevalence
      of SEN virus DNA in donated blood samples.

PMID- 19112741
TI  - The do's and don'ts of helping the impaired nurse.

PMID- 19112742
TI  - A culture of learning.

PMID- 19112743
TI  - The importance of awareness of nursing students' denotative images of nursing.
AB  - The aim of this article is to describe the images that recent nursing students in
      Eurocentric culture have of nursing and discuss how these images can be used to
      highlight nurses' authority and autonomy in comparison with the medical
      profession. The empirical material consists of short narratives from 168 nursing
      students. Three themes emerged from the categories of answers: The Nurse as an
      Idealistic Helper, The Nurse as a Realistic Developer, and The Nurse as a Young
      Seeker. The essence of nursing could be traced in these themes even if a solid
      ground of nursing shows itself in changing forms. According to this study and
      previous research, nursing can be considered as a mummified occupation in its
      essence, given that the old values and stereotypes largely remain. The main
      motives for becoming a nurse are altruism, a desire for autonomy, and
      flexibility. To strengthen the profession, both teachers and clinical supervisors
      should use the students' images of nursing as a starting point in nursing
      education and develop them in different contexts.

PMID- 19112744
TI  - Transitioning foreign-educated physicians to nurses: the New Americans in Nursing
      accelerated program.
AB  - The innovative New Americans in Nursing accelerated program targets foreign
      educated physicians (FEPs) residing in the United States who are either
      unemployed or underemployed and desire to become nurses. With a five-semester
      baccalaureate nursing curriculum, students are awarded credit for general
      education and science prerequisite courses completed in medical school and
      matriculate for 63 credits of nursing courses. Measurement of program outcomes
      provides evidence that FEPs socialize to nursing at the same level, exhibit
      significantly greater critical thinking skills, and have higher NCLEX-RN pass
      rates than generic baccalaureate nursing students. The program is a valuable
      option not only in addressing the critical and continuing nursing shortage, but
      also in diversifying the nursing workforce in response to health disparities and
      the increasing diversity of the U.S. population.

PMID- 19112745
TI  - Changing nursing culture to welcome second-degree students: herding and
      corralling sacred cows.
AB  - Accelerated nursing programs necessitate new learning approaches that challenge
      stubborn sacred cows because bright second-degree students have high
      expectations. Myths about nursing education may hinder innovation in accelerated
      programs. Mezirow's theoretical model of transformational learning provides a
      framework for streamlining nursing education for second-degree students.

PMID- 19112746
TI  - Patient simulator sessions and critical thinking.
AB  - The project purpose was to determine whether measures of critical thinking show
      differences between three groups (simulator, non-simulator, control) of
      baccalaureate nursing students. The second purpose was to determine the
      moderating effect of students' preferred learning style. All groups experienced a
      moderate to large effect size in critical thinking scores. The corrected model
      for the total scale gain score was statistically significant but not significant
      for learning style or group.

PMID- 19112747
TI  - Opinions of adult learners about negotiating syllabi rules in a baccalaureate
      nursing program.
AB  - A baccalaureate nursing (BSN) program is using the philosophy of adult learning
      as a tenet of curriculum development. This philosophical approach is to support
      the uniqueness of the adult learner. Are nursing faculty composing course syllabi
      in a way that allows accommodations for adult learners' complex lives? Which
      syllabi items, if any, would adult learners negotiate? This descriptive study was
      part of a larger study conducted by the same researchers that compared nursing
      faculty and student expectations of syllabi. One hundred ninety-nine BSN students
      reported they would ask for syllabi accommodations and identified the rationale
      for doing so. The most frequently selected accommodation to be negotiated was
      assignment deadlines (46%), followed by attendance requirements (35%) and testing
      deadlines (28%). Personal or family issues was identified by more than 80% of
      students as the reason they would request a change.

PMID- 19112748
TI  - Is nursing ready for WebQuests?
AB  - Based on an inquiry-oriented framework, WebQuests facilitate the construction of
      effective learning activities. Developed by Bernie Dodge and Tom March in 1995 at
      the San Diego State University, WebQuests have gained worldwide popularity among
      educators in the kindergarten through grade 12 educational sector. However, their
      application at the college and university levels is not well documented.
      WebQuests enhance and promote higher order-thinking skills, are consistent with
      Bloom's Taxonomy, and reflect a learner-centered instructional methodology
      (constructivism). They are based on solid theoretical foundations and promote
      critical thinking, inquiry, and problem solving. There is a role for WebQuests in
      nursing education. A WebQuest example is described in this article.

PMID- 19112749
TI  - The Schumacher model: fostering scholarship and excellence in nursing and for
      recruiting and grooming new faculty.
AB  - In 2004, U.S. nursing schools turned away 32,797 qualified nursing applicants.
      One contributing factor was an insufficient number of nursing faculty. Projected
      retirements will require nursing faculty units to work in smaller numbers and
      actively recruit new faculty. The Schumacher model provides a framework for
      fostering scholarship and excellence in nursing and for recruiting and grooming
      new faculty. It articulates methods for nurse educators to capitalize on each
      other's strengths to work together to address the current shortage. This article
      describes the Schumacher model, its application to mentorship among nursing
      faculty, and the current nursing faculty climate.

PMID- 19112750
TI  - Syllabus selection: innovative learning activity.

PMID- 19112751
TI  - Happiness at work.

PMID- 19112752
TI  - Hopeless.

PMID- 19112753
TI  - Advance directives: following the patient's wishes.

PMID- 19112754
TI  - Regional diversity in Florida's nurse supply, demand, and education.

PMID- 19112755
TI  - Our bodies and the legacy of "better living through chemistry".

PMID- 19112756
TI  - Efficacy of adalimumab in plaque psoriasis: experience on 28 patients.
AB  - Psoriasis is a common, chronic inflammatory skin disease with arthritis that may
      occur in a percentage of patients that varies between 5% and 42%. Many systemic
      agents as cyclosporine, methotrexate, acitretin, and photochemotherapy have been
      used for the treatment of patients affected by moderate-to-severe plaque
      psoriasis although they present side effects (ie, cumulative organ toxicity and
      lack of efficacy over time) that limit long-term use. Significant therapeutical
      improvement has been obtained introducing biological therapies, designed to
      modify and regulate immunological processes by targeting specific molecules
      involved in the immunopathogenesis of psoriasis. Adalimumab is a fully human
      recombinant antibody against tumor necrosis factor-alpha (TNF-alpha). To date,
      there is not much data available on the efficacy and safety of adalimumab in
      patients affected by moderate-to-severe plaque psoriasis. The authors report our
      first experience on the efficacy and safety of adalimumab in monotherapy at a
      dose of 40 mg every-other-week for the treatment of plaque psoriasis in patients
      with or without arthritis. Twenty-eight patients were treated for a period of 48
      months. It was observed an improvement of the psoriasis condition as well as of
      patients' quality of life and mood state.

PMID- 19112758
TI  - Treatment of moderate to severe plaque psoriasis with concomitant efalizumab and
      narrow-band ultraviolet B phototherapy.
AB  - BACKGROUND: Efalizumab therapy and narrow-band ultraviolet B (NB-UVB)
      phototherapy have different mechanisms of action; combined therapy may be more
      effective than either treatment alone in treating moderate to severe plaque
      psoriasis. METHODS: This study investigated the efficacy and safety of efalizumab
      (1 mg/kg/wk) combined with NB-UVB 3 times a week for 12 weeks, followed by
      efalizumab monotherapy for 12 additional weeks. RESULTS: Twenty patients were
      enrolled with mean Psoriasis Area and Severity Index (PASI) of 12.8 +/- 7.4, mean
      physician's global assessment (PGA) of 5 +/- 1, and mean body surface area (BSA)
      affected of 18.2% +/- 15.3% at baseline. At week 12, 65% of patients (n = 13)
      achieved PASI 75; mean PGA was 2 +/- 1, corresponding to a 60% reduction; and
      mean BSA was 4.7% +/- 4.1%, corresponding to a 74% reduction. The improvements
      seen at week 12 were maintained during the ensuing efalizumab monotherapy.
      CONCLUSION: Combination of efalizumab and NB-UVB followed by efalizumab
      monotherapy was effective and well tolerated, this warranting further
      investigation.

PMID- 19112757
TI  - Etanercept in the treatment of palmoplantar pustulosis.
AB  - INTRODUCTION: Palmoplantar pustulosis (PPP) is a chronic, recurrent and difficult
      to treat skin condition characterized by the presence of pustules, erythema, and
      hyperkeratosis on palms and soles. METHODS: Fifteen subjects with PPP were
      randomized (2:1) to receive subcutaneous injections of either etanercept 50 mg or
      a placebo twice a week for 3 months. All subjects then received the etanercept 50
      mg injections twice a week for an additional 3 months. RESULTS: Etanercept was
      well tolerated by subjects with PPP. The decrease in median Palmoplantar
      Pustulosis Area and Severity Index (PPPASI) score from baseline to 24 weeks was
      statistically significant for subjects treated with etanercept for 24 weeks (P =
      0.038, n = 10) but not for subjects in the placebo/etanercept cross-over group (P
      = 0.125, n = 5). Comparison of changes in PPPASI from baseline to week 12 was not
      statistically significant for subjects assigned to etanercept or to placebo. Some
      subjects treated with etanercept presented good clinical improvements in PPP
      severity whereas others showed an increase in PPP severity. CONCLUSION: This
      study showed that etanercept was well tolerated in subjects with PPP and suggests
      that some PPP subjects might benefit from etanercept therapy. Larger studies are
      needed to assess PPP response to etanercept including the influence of smoking
      and the presence or absence of psoriasis outside palms and soles.

PMID- 19112759
TI  - Topical tetracycline in the treatment of acne vulgaris.
AB  - BACKGROUND: Topical tetracycline was the first topical antibiotic approved for
      the treatment of acne, its use has been limited because of the skin penetration
      problems of the active ingredient. OBJECTIVES: The objective of this study was to
      evaluate the effectiveness of a new formulation of topical tetracycline [Imex,
      tetracycline hydrochloride 3%, 20g] monotherapy in the treatment of mild to
      moderate acne vulgaris. METHODS: The sample group consisted of 87 volunteer
      students of both sexes with grade 1 to grade 2 acne as assessed by Investigator's
      Global Assessment (IGA) severity grading system. Subjects were instructed to
      apply topical tetracycline twice daily for 8 weeks. Subject were evaluated at
      baseline and at weeks 2, 4, and 8. RESULTS: Of 87 subjects, 68 completed the 8
      week treatment period. The mean reduction rates of opened comedones were 55.4%,
      closed comedones were 27.1%, papules were 24.8%, pustules were 27.3%. After 8
      weeks of treatment, a statistically significant reduction was only observed in
      the mean counts of the papules and pustules (P < 0.001). CONCLUSION: Tetracycline
      is a well-tolerated topical agent and is particularly effective in the treatment
      of inflammatory lesions in acne.

PMID- 19112760
TI  - Expression of CD70 and the TH17 transcription factor RORgammaT in human contact
      dermatitis.
AB  - Contact sensitizers are a major cause of inflammatory skin disease and as topical
      immunomodulators also have the potential for treating cancer, viral diseases and
      certain autoimmune disorders. In the present study, the authors identify the
      upregulation of the TH17 lymphocyte subset transcription factor retinoid orphan
      receptor gamma T (RORgammaT) and the CD70 costimulatory pathway in human contact
      sensitivity (CS) using molecular techniques. Identification of this important new
      subset of T lymphocytes and a recognized costimulatory pathway offers potential
      for ameliorating CS and insight into antitumor and antiviral mechanism of haptens
      as topical immunomodulators.

PMID- 19112762
TI  - Verrucous linear (segmental) psoriasis of the right leg responding to radiation
      therapy.
AB  - Verrucous linear segmental psoriasis (VLSP) is invariably recalcitrant to
      treatment. It is a distinct variant of psoriasis that frequently is considered a
      form of a verrucous linear, epidermal nevus. The hypertrophic nature of the
      plaques makes treatment particularly challenging. The authors present a case of
      verrucous linear psoriasis of the right leg that responded to radiation therapy.

PMID- 19112761
TI  - Relapse of acne following isotretinoin treatment: a retrospective study of 405
      patients.
AB  - BACKGROUND: Isotretinoin is the most effective systemic treatment option for
      patients with nodulocystic acne or acne vulgaris who have failed a treatment with
      systemic antibiotics. METHODS: We conducted a retrospective study of 405 acne
      patients treated with isotretinoin to evaluate the incidence of recurrence after
      a course of at least 150 mg/kg of isotretinoin. RESULTS: Of the 405 patients
      evaluated, 94 (23.2%) experienced relapses severe enough for the patient to
      request further medical management. Of the 94 patients, 76 (80.9%) relapsed
      within the first 2 years following completion of a course of isotretinoin.
      LIMITATIONS: This was a retrospective study at a single practice site.
      CONCLUSION: Almost one-fifth of patients have a recurrence of acne within the
      first 2 years. Patients should be made aware of this information, as it will
      contribute to the development of accurate and appropriate expectations of
      therapy.

PMID- 19112763
TI  - Psoriasis and psoriatic arthritis in a patient with HIV: response to
      mycophenolate mofetil treatment.
AB  - A case of psoriasis and psoriatic arthritis in a 38-year-old white male patient
      infected with human immunodeficiency virus (HIV) treated safely and effectively
      with mycophenolate mofetil (MMF) is reported. Treatments for psoriasis and
      psoriatic arthritis are manifold, including topical, oral, intramuscular,
      intravenous, and subcutaneous therapies. These indicated treatments for psoriasis
      and psoriatic arthritis result in suppression of the immune system.

PMID- 19112764
TI  - Pustular psoriasis following treatment of rheumatoid arthritis with TNF-alpha
      inhibitors.

PMID- 19112765
TI  - Pityriasis rubra pilaris with epidermolytic hyperkeratosis.

PMID- 19112766
TI  - Refractory dissecting cellulitis of the scalp treated with adalimumab.
AB  - Dissecting cellulitis of the scalp (DCS) is a suppurative, neutrophillic
      dermatosis. Therapies typically provide short-term improvement and include
      antibiotics, prednisone, and isotretinoin, as well as radiation, surgical
      excision, and laser ablation. The authors report the use of the tumor necrosis
      factor (TNF) blocker, adalimumab, to successfully treat a 39-year-old male with a
      long-standing history of DCS.

PMID- 19112767
TI  - Severe erythroderma in a patient under intermittent therapy with efalizumab.
AB  - The author presents the case of a 27-year-old man who suffered 2 episodes of
      erythroderma while on therapy with efalizumab for psoriasis. The first episode,
      occurred 2 weeks after the first dose, was well controlled without discontinuing
      the drug. A second erythrodermic flare was observed after 4 weeks following
      efalizumab reintroduction. In this case, oral methotrexate was administered as
      monotherapy during 4 months, and then was tapered off and efalizumab again
      reintroduced for continuous treatment for a period 14 months with excellent
      results. This second episode of erythroderma was clinically accompanied by a
      marked hyperkeratosis, blepharitis, and nasal infection due to Staphylococcus
      aureus. Lymphocytosis and leukocyturia with negative urine culture were also
      reported in both episodes. As a result, it was concluded that the erythroderma
      was an adverse reaction to efalizumab that could be solved without treatment
      discontinuation. The author considered this patient as a good responder to
      continuous treatment with efalizumab.

PMID- 19112768
TI  - Etanercept in therapy multiresistant overlapping pityriasis lichenoides.
AB  - INTRODUCTION: Pityriasis lichenoides (PL) exhibits a protean clinical
      presentation, particularly in its overlapping form (OPL) combining aspects of the
      acute and chronic types. Some patients are drug multiresistant and pose a
      therapeutic dilemma. The anti-tumor necrosis factor (TNF)-alpha agent etanercept,
      was recently introduced as an alternative treatment for psoriasis, rheumatoid
      arthritis, and psoriatic arthritis. CASE REPORT: A 65-year-old woman suffered
      from an overlapping form of pityriasis lichenoides (OPL) for 5 years. Several
      initial acute episodes were controlled by successive courses of oral antibiotics,
      topical corticosteroids, and/or psoralen ultraviolet light-A (PUVA) therapy. The
      disease progressively evolved to a more chronic form. Topical immune response
      modifiers and corticosteroids, as well as PUVA, ultraviolet light-B (UVB),
      methotrexate, dapsone, and cyclosporine were introduced, but all proved
      ineffective. Due to the therapy multiresistance, 2 weekly injections of
      etanercept were administered. After 2 months, a marked improvement was observed
      in regards to the patient's pruritus and inflammation. No treatment-related
      adverse effects were observed. Therapy was continued for 4 months without any new
      lesion development. However, 1 month after stopping treatment new OPL lesions
      recurred. CONCLUSION: At the time of publication, this is the first report of the
      effectiveness of etanercept in OPL. This drug might be considered as a
      therapeutic alternative for treatment multiresistant OPL.

PMID- 19112769
TI  - When wound healing goes awry. A review of normal and abnormal wound healing, scar
      pathophysiology, and therapeutics.

PMID- 19112770
TI  - Retrograde transport and transcytosis of botulinum toxin serotypes to the brain:
      analysis of potential neurotoxicity.

PMID- 19112771
TI  - Percutaneous cardiovascular intervention. The time has come for a big change...

PMID- 19112772
TI  - Chronic total coronary occlusions and the occluded artery trial. A critical
      appraisal.

PMID- 19112773
TI  - Last nail in the coffin of late lumen loss?

PMID- 19112774
TI  - Together we achieve more...

PMID- 19112775
TI  - Why don't we return to bare metal stents?

PMID- 19112776
TI  - Why we should never return to bare metal stents?

PMID- 19112777
TI  - Cardiovascular repair and regeneration 2008: the fourth International Conference
      on Cell Therapy for Cardiovascular Disease (IC3D).
AB  - The principal lessons and take-home points from IC3D are: 1) clinical trials are
      in an expansion stage, being constructed upon the substantial foundation of the
      international experience of the last 6-7 years, and now looking at hard clinical
      endpoints, 2) catheter-based cell-delivery is likely to be the mainstay of
      clinical trials and, in time, clinical practice, 3) the coming year will bring
      light to techniques for enhancing cell function (autologous or allogeneic),
      improving tissue receptivity to cell delivery and facilitating the performance
      catheter-based procedures. While the role of cell-therapy in clinical practice is
      yet to be established, signals from existing data indicate that engagement of the
      interventional cardiology community in this field should be expanded.

PMID- 19112778
TI  - Highlights from ICI--Innovations in Cardiovascular Interventions. December 3-5,
      2007, Tel Aviv, Israel.

PMID- 19112779
TI  - EXCELLA First-in-Man (FIM) study: safety and efficacy of novolimus-eluting stent
      in de novo coronary lesions.
AB  - AIMS: First generation DES have markedly reduced restenosis. However, there is a
      major interest in developing new DES with greater flexibility, radiopacity and
      safety profile. The Elixir Medical drug eluting stent is a novel DES that
      combines a chromium-cobalt platform with novolimus (an antiproliferative
      sirolimus-analogue drug) and a polymer from the methacrylate family. As potential
      advantages, it provides a lower drug dose as compared to Cypher (85 microg of
      novolimus vs. 140 microg of sirolimus) and therefore has a lower polymer load. We
      sought to evaluate the safety and efficacy of this novel device in reducing
      neointimal hyperplasia as assessed by QCA and IVUS. METHODS AND RESULTS: In April
      2007 a consecutive cohort of patients with de novo lesions < or = 14 mm in
      length, located in native coronaries of diameter from 3.0 to 3.5 mm were
      consecutively enrolled in this First-in-Man study (FIM). By protocol, angiography
      and IVUS would be done at baseline and repeated at four and eight months. Dual
      anti-platelet therapy was maintained for a minimum of 12 months. The primary
      endpoint was QCA lumen loss at 4-month follow-up. Secondary endpoints included
      MACE, in-stent neointimal obstruction by IVUS and device success. A total of 15
      patients were included with 67% female patients and diabetes was detected in 47%
      of the cohort. Angiographic and procedural success was achieved in all patients.
      At 4-month angiographic follow-up there was in-stent late lumen loss (0.15 +/-
      0.29 mm) by QCA and % volume obstruction (2.6 +/- 2.6) by IVUS. The angiographic
      in-stent late lumen loss results at eight months were 0.31 +/- 0.25 mm and %
      volume obstruction by IVUS was 6.0 +/- 4.4%. Late incomplete stent apposition
      (ISA) were not observed among these patients and no MACE was evidenced through
      nine month clinical follow-up. CONCLUSIONS: In this FIM study, implantation of
      the novolimus-eluting stent was proven to be feasible, safe and elicited minimum
      neointimal proliferation. Additional large clinical trials should be considered
      to confirm these promising results.

PMID- 19112780
TI  - Biodegradable-polymer-based, sirolimus-eluting Supralimus stent: 6-month
      angiographic and 30-month clinical follow-up results from the series I
      prospective study.
AB  - AIMS: There have been recent concerns regarding the long-term safety of the first
      generation of drug-eluting stents, which utilised a permanent polymer coating for
      drug delivery. SERIES I is a prospective, non-randomised, first-in-man open label
      study with the biodegradable polymer-based Supralimus sirolimus eluting stent
      (Sahajanand Medical Technologies Pvt. Ltd, India) for the treatment of patients
      with coronary artery lesions. METHODS AND RESULTS: One hundred patients were
      treated with 126 Supralimus stents (mean lesion length 10.5 +/- 4.3 mm, mean
      reference vessel diameter 2.66 +/- 0.62 mm). The pre-specified primary endpoint
      was angiographic binary in-stent restenosis at six months. Secondary endpoints
      were device-orientated major adverse clinical events (MACE; defined as a
      composite of cardiac death, nonfatal myocardial infarction [Q-wave and Non-Q
      wave], or clinically-justified target vessel revascularisation) at 30 days, nine
      months and 30 months. Angiographic follow-up in a pre-specified subgroup of 60
      patients at six months showed binary angiographic restenosis rates of 0% (in
      stent) and 1.7% (in-segment). The in-stent late loss was 0.09 +/- 0.37 mm. MACE
      rates were 0% after one month, 6% at 9-month follow-up and 7% after 30 months
      follow-up. CONCLUSIONS: The biodegradable-polymer-based sirolimus-eluting stent
      (Supralimus) is effective in inhibiting neointimal hyperplasia.

PMID- 19112781
TI  - Two year follow-up after primary PCI with a paclitaxel-eluting stent versus a
      bare-metal stent for acute ST-elevation myocardial infarction (the PASSION
      trial): a follow-up study.
AB  - AIMS: This follow-up study was performed to assess the long-term effects of
      paclitaxel-eluting stents (PES) compared with bare-metal stents (BMS) in patients
      who had undergone a percutaneous coronary intervention (PCI) for ST-elevation
      myocardial infarction (STEMI). METHODS AND RESULTS: The PASSION trial randomly
      assigned 619 patients with STEMI to receive either a PES or BMS. The composite
      endpoint for the follow-up study was the occurrence of the combination of cardiac
      death, recurrent myocardial infarction, target lesion revascularisation (TLR) or
      stent thrombosis at two years. A trend towards a lower rate of the composite
      endpoint was observed in the PES compared to the BMS group (hazard ratio [HR]
      0.70; 95% C.I. 0.45-1.09). This was driven by a reduced TLR in favour of PES (HR
      0.60; 95% C.I. 0.34-1.09). Angiographically proven stent thrombosis at two years
      did not differ significantly between groups (2.1% in the PES group versus 1.4%;
      HR 1.48; 95% C.I. 0.42-5.23). CONCLUSIONS: PES implantation for STEMI did not
      significantly improve clinical outcome at two years after the index event,
      although there was a trend towards a lower rate of target-lesion
      revascularisation. The rate of stent thrombosis did not differ significantly
      between groups.

PMID- 19112782
TI  - Novel drug eluting stent system for customised treatment of coronary lesions:
      CUSTOM I feasibility trial 24 month results.
AB  - AIMS: The Custom NX 36 Drug Eluting Stent (DES) System is designed to treat
      coronary lesions via in situ stent length customisation. The stent evaluated in
      this study consists of nine interdigitated stent segments, each 4 mm in length,
      coated with a biodegradable formulation of Biolimus A9 and Poly-Lactic-Acid, a
      biodegradable drug carrier, and loaded into a unique sheath protected, integrated
      balloon delivery system. METHODS AND RESULTS: The objective of this non
      randomised prospective multicentre CUSTOM I Trial was to demonstrate the safety
      of in situ stent length customisation in 30 consecutive patients. Angiographic
      (QCA) and intravascular ultrasound (IVUS) follow-up was performed at two cohort
      time intervals: four (n=10) or eight (n=20) months. Mean lesion length and
      reference vessel diameters were 17.7 +/- 9.6 mm and 2.6 +/- 0.3 mm, respectively.
      Procedural success was 93%. There were three MACEs in the study population from
      enrollment through to twenty-four month follow-up. The in-hospital MACE rate was
      2/30, with non-Q-wave myocardial infarctions events in two patients who recovered
      without further sequelae. At five months, one patient who had crossed over
      initially to PTCA required CABG surgery. Results from QCA and IVUS assessments at
      four and eight months showed no binary restenosis, mean in-stent late luminal
      loss of 0.25 +/- 0.23 mm and 0.26 +/- 0.23 mm. CONCLUSIONS: This first evaluation
      of the new customisable Biolimus A9-eluting Custom NX stent suggests safety and
      efficacy through twenty-four month follow-up. Further evaluations are warranted
      to confirm the overall favourable outcomes.

PMID- 19112783
TI  - Diabetic patients treated for unprotected left main coronary artery disease with
      drug eluting stents: a 3-year clinical outcome study. The diabetes and drug
      eluting stent for LeFT main registry (D-DELFT).
AB  - AIMS: Diabetes mellitus (DM) plays an important role in the development of
      coronary artery disease. Although previous studies have associated drug-eluting
      stent (DES) implantation in diabetic patients with favourable clinical and
      angiographic outcomes, the very long-term efficacy of these devices in diabetic
      patients undergoing PCI for significant unprotected left main coronary artery
      (ULMCA) disease has not been established yet. METHODS AND RESULTS: Consecutive
      diabetic patients (n=100), who underwent elective PCI with DES for de novo
      lesions in an ULMCA between April 2002 and April 2004 in seven tertiary health
      care centres, were identified retrospectively and analysed. Consecutive non
      diabetic patients (n=193), who underwent elective DES implantation for
      unprotected ULMCA disease, were selected as a control group. All patients were
      followed for at least 36 months. At 3-years follow-up, freedom from cardiac death
      & myocardial infarction (CDMI), target lesion revascularisation (TLR) and target
      vessel revascularisation (TVR) did not differ significantly between groups. The
      adjusted freedom from major adverse cardiac events (MACE, defined as the
      occurrence of CD, MI or TVR) was 63.4% in the DM group and 77.6% in the controls
      (p<0.001). When divided into IDDM and NIDDM sub-groups, insulin-dependent DM
      (IDDM) but not non IDDM (NIDDM) patients had significantly lower freedom from
      CDMI, TLR, TVR and MACE compared to controls. CONCLUSIONS: These results suggest
      that major improvements in DES technology and pharmacotherapy are still required
      to improve clinical outcome and that the decision to perform percutaneous
      revascularisation in this subset of patients should be taken cautiously and on a
      case by case basis.

PMID- 19112784
TI  - European experience with the retrograde approach for the recanalisation of
      coronary artery chronic total occlusions. A report on behalf of the euroCTO club.
AB  - AIMS: Recanalisation rates of coronary chronic total occlusions (CTO) remain sub
      optimal. The retrograde technique was recently introduced to improve success
      rates. METHODS AND RESULTS: From February 2005 until December 2007, 175 patients
      were treated with this technique in seven European centres by highly experienced
      operators: in 84 (48%) as primary strategy, in 41 (23.5%) immediately after
      antegrade failure and in 50 (28.5%) as a repeat procedure after previous
      antegrade failure. Baseline characteristics revealed a mean age 61.4 +/- 10.8
      years with 29.5% and 39% of patients having diabetes and a prior history of MI,
      respectively. The mean occlusion duration was 50.8 months (determined in 32% of
      patients). The target vessel was: LAD 21%, LCX 6.3%, RCA 71.4%. Epicardial
      collaterals were accessed in 20.6% and septal in 79.4% of the patients. Overall
      success rate was 83.4%. In 80.6% a wire crossed the collaterals and successfully
      delivered distal to the occlusion; success rate in this group was 91.5%. The
      technique implemented in the retrograde facilitated successful recanalisation
      was: retrograde wire/balloon crossing in 28%, CART in 34% and marker
      wire/"knuckle" technique in 48%. There was a great diversity between centres
      referring to the retrograde technique used. According to the initial strategy
      success rates were: primary 89.3%, immediately after antegrade failure 65.9% and
      repeat procedure after antegrade failure in 88%. In patients with failure to
      cross the collaterals success rate was 50%. Septal rupture/haematoma occurred in
      6.9% of the patients, periprocedural myocardial infarction (CK-MB rise) in 4% and
      TIA in 0.6% and wire entrapment in 0.6%. Mean fluoroscopy time was 59.3 mn and
      the mean contrast used was 420.9 ml. Drug eluting stents were implanted in all
      successfully recanalised vessels. CONCLUSIONS: There is great diversity amongst
      European centres with respect to how the retrograde strategy has been adopted and
      adapted. The retrograde approach was used with high degree of success and safety
      and can thus be regarded as a valid contributor to the armamentarium of the
      modern day interventional cardiologist.

PMID- 19112785
TI  - Impact of bifurcation lesions on clinical outcome and prognosis of primary
      angioplasty in acute myocardial infarction.
AB  - AIMS: The aim of this study was to determine the impact of bifurcation lesions on
      outcomes after primary percutaneous intervention (PCI) for acute myocardial
      infarction. METHODS AND RESULTS: We retrospectively reviewed a single-centre
      database of 646 patients admitted for primary angioplasty within 12 hours after
      AMI. We compared baseline characteristics and outcomes between bifurcation and
      non-bifurcation lesions. Bifurcation lesions were found in 23% of patients. They
      predominantly involved the left anterior descending artery. Provisional T
      stenting was used in 89.3% of patients (with stenting of the main branch in 82%
      and of both branches in 7.3%), side-branch protection in 54.6%, and final kissing
      balloon inflation in 33%. The procedural success rate was 92% for the main branch
      of bifurcation lesions compared with 93% for non-bifurcation lesions (P=0.65).
      Major adverse cardiac event (MACE) rates were comparable in the two groups: in
      hospital MACE was 13.3% in the bifurcation group versus 11.4% in the non
      bifurcation group (P=0.72), and the 1-year total MACE rate was 22.6% in the
      bifurcation group versus 19.5% in the non-bifurcation group (P=0.56).
      CONCLUSIONS: Bifurcation lesions are common in patients with AMI. In a population
      with AMI, immediate and mid-term outcomes of primary PCI were similar in patients
      with and without bifurcation lesions.

PMID- 19112786
TI  - Proof-of-concept trial to evaluate haemoglobin based oxygen therapeutics in
      elective percutaneous coronary revascularisation. Rationale, protocol design and
      haemodynamic results.
AB  - AIMS: To test the hypothesis that intracoronary infusion of pre-oxygenated HBOC
      201 during brief, total coronary artery occlusion would preserve left ventricular
      function. METHODS: Immediately following a successful PCI, the target coronary
      artery was occluded without ("dry occlusion")--or with--infusion of pre
      oxygenated HBOC-201 distal to the stent via the guidewire shaft of an over-the
      wire balloon for up to three minutes at an infusion rate of 48 ml/min. A cross
      over design was applied. Early signs of myocardial ischaemia were evaluated by
      left ventricular pressure-volume loops and intracoronary ECG. A 12-lead Holter
      ECG was activated before the PCI and deactivated four hours after the study
      period. Primary endpoints were change in left ventricular relaxation indices and
      in the sum of ST segment deviations. RESULTS: None of the measured parameters
      differed significantly from their respective baseline values during HBOC-201
      infusion. By contrast, ejection fraction (EF), cardiac output (CO) and minimal
      rate of LV pressure change (dP/dTMIN) decreased significantly and the end
      diastolic pressure (EDP) and time constant of relaxation increased significantly
      during dry occlusions (P<0.05). The end diastolic pressure-volume relationship
      (EDPVR) at the fixed pressure level of 30 mmHg (V30), an index of myocardial
      compliance, reflected greater myocardial stiffness during dry occlusions compared
      to occlusions with HBOC-201 infusion. CONCLUSIONS: Intracoronary infusion of
      oxygenated HBOC-201 is capable of preserving left ventricular function, likely
      through maintenance of myocardial oxygenation. It is hypothesised, that in an
      acute setting, HBOC-201 could serve as an oxygen bridge to reperfusion by PCI
      extending the "golden" time period during which permanent myocardial damage is
      unlikely.

PMID- 19112788
TI  - The role of thrombectomy and distal protection devices during percutaneous
      coronary interventions.
AB  - AIMS: Achievement of the angiographic gold standard TIMI 3 flow (Thrombolysis in
      Myocardial Infarction) flow grade during PCI (percutaneous coronary intervention)
      in the setting of AMI (acute myocardial infarction) is insufficient for
      attainment of optimal prognostic benefit, as there is a poor prognosis for
      patients with evidence of inadequate flow at the tissue level despite patent
      coronary arteries. PCI in lesions containing thrombus are associated with an
      increased risk of complications occurring through dislodgement of thrombotic
      material resulting and distal embolisation leading to slow flow or even no
      reflow. Devices which remove thrombus from coronary arteries (thrombectomy
      devices) or protect from distal embolisation of thrombus (distal protection
      devices) are increasingly used in PCI. METHODS AND RESULTS: We have performed a
      systematic review of the literature to investigate the role of these devices in
      PCI in the setting of AMI. Use of thrombectomy devices in randomised and
      multicentre trials in patients undergoing PCI during STEMI is associated with a
      significant benefit in a number of markers of myocardial perfusion including MBG
      (myocardial blush grade), ST segment resolution and improvement of distal
      embolisation, although no significant benefits in mortality have been observed.
      CONCLUSIONS: There does not appear to be strong evidence for the use of embolic
      protection devices and distal filter devices in the setting of primary PCI in
      native coronary arteries, although evidence from trials such as the SAFER trial
      would make a strong case for their use in SVG interventions.

PMID- 19112787
TI  - Beneficial 2-years results of drug-eluting stents in saphenous vein graft
      lesions.
AB  - AIMS: There are limited data regarding clinical outcomes of drug-eluting stents
      (DES) in saphenous vein grafts (SVGs) compared to bare metal stents (BMS). Here
      we compared outcomes of DES in de novo SVG lesions versus BMS in contemporary
      percutaneous coronary intervention (PCI). METHODS AND RESULTS: We compared in
      hospital, 6-month, 1-year and two years outcomes in 68 patients (72 grafts) who
      underwent PCI of SVG lesions using DES and a control BMS group composed of 43
      patients (46 grafts) who underwent angioplasty in de novo SVG lesions. Major
      adverse cardiac events (MACE) included death, myocardial infarction (MI), target
      lesion revascularisation (TLR), and target vessel revascularisation (TVR). The
      rates of TLR and TVR at the 1-year evaluation were lower in the DES group than
      the BMS group (TLR per patient, 7.4% vs. 21%, P=0.04; TVR per patient, 10.3% vs.
      23.3%, P=0.1). MACE-free survival was 88.2% in the DES group and 69.8% in the BMS
      group (P=0.02). At two years clinical follow-up: death 2.9% vs. 4.7% (P=0.6); MI:
      8.8% vs. 7% (P=0.6). The rates of TLR and TVR were significantly lower in the DES
      group compared to the BMS group (TLR per patient, 14.7% vs. 32.6%, P=0.03; TVR
      per patient, 10.3% vs. 27.9%, P=0.02). The rate of MACE-free survival was 79.4%
      in the DES group and 58.1% in the BMS group (P=0.02). Between one to two years
      after PCI, no cases of angiographic stent thrombosis were recorded in either
      group. CONCLUSIONS: DES implantation in SVG lesions was safe and had favourable
      outcomes after two years without excess cardiac mortality.

PMID- 19112789
TI  - Lower levels of in-stent late loss are not associated with the risk of stent
      thrombosis in patients receiving drug-eluting stents.
AB  - AIMS: The aim of this study was to evaluate whether there is any relationship
      between in-stent late loss (ISLL) and the risk of stent thrombosis (ST) in
      patients treated with drug eluting stents (DES). The benefit of DES in reducing
      binary angiographic restenosis and the need for new revascularisation procedures
      is due to a reduction on ISLL. It has been hypothesised, however, that neointimal
      hyperplasia could preclude ST, and thus a very low ISLL could increase the risk
      of ST. METHODS AND RESULTS: We selected 26 randomised clinical trials comparing
      bare metal stents and DES or different DES types, and including clinical and
      angiographic follow-up. In order to evaluate the association between risk of ST
      and ISLL, meta-regression analyses were conducted, weighting for the number of
      patients of each study. Twenty-six studies were included, retrieving 36 subgroups
      for analysis and 8,971 patients treated with DES. The incidence for ST and LST
      was 0.81% and 0.17%. Using meta-regression techniques, neither the risk of ST nor
      the risk of LST were found to be significantly associated with ISLL, accounting
      for -0.82 and -0.002 meta-regression estimates respectively (IC 95%: -1.92 to
      0.28 for ST and -0.008 to 0.003 for LST). CONCLUSIONS: The risk of ST and LST
      after DES implantation is not related with ISLL values. A very low mean value of
      ISLL is nor associated with a higher risk of ST.

PMID- 19112790
TI  - Recovery and functional activity of mononuclear bone marrow and peripheral blood
      cells after different cell isolation protocols used in clinical trials for cell
      therapy after acute myocardial infarction.
AB  - AIMS: Clinical trials showed contradictory results in functional recovery after
      intracoronary infusion of autologous mononuclear (bone marrow) cells in patients
      with acute myocardial infarction. A recent study suggests that this might be
      related to the isolation protocol used. In The Netherlands, a comparable
      randomised multicentre trial (HEBE) was designed. To validate the isolation
      method of bone marrow and peripheral blood-derived mononuclear cells, we compared
      our processing protocol with methods comparable to the ASTAMI (no beneficial
      effect) and the REPAIR-AMI study (beneficial effect). METHODS AND RESULTS: The
      effect of several factors (density gradient, washing buffer and centrifugation
      speed) has been studied on recovery and function (migration and clonogenic
      capacity) of mononuclear cells. Significantly lower cell recoveries were found at
      a centrifugation speed of 250 g, compared to 600 or 800 g, respectively.
      Furthermore, washing buffer without supplemented human serum albumin and heparin
      resulted in significantly lower cell recovery and functional impairment as
      measured by clonogenic capacity. CONCLUSIONS: The results of our study justify
      the cell-processing protocol as applied in the HEBE trial (600 g, human serum
      albumin supplemented washing buffer). This protocol results in viable and
      functional cells of which the quantity and quality is at least comparable to a
      successful study like the REPAIR-AMI.

PMID- 19112791
TI  - The neointimal response to stents eluting tacrolimus from a degradable coating
      depends on the balance between polymer degradation and drug release.
AB  - AIMS: To study how the balance between tacrolimus elution and polymer degradation
      from drug-eluting stents (DES) affects neointimal thickening (NIT) in swine
      coronary arteries. METHODS AND RESULTS: We assessed a fast-degrading high dose (2
      microg/mm2), a slow degrading low dose (1 microg/mm2) or polymer-only coated DES
      (Pol) versus bare metal stent (BMS). Coronary segments were pre-injured with a
      balloon/artery ratio of 1.1 to 1.3. Then stents were implanted at that site with
      a stent/artery ratio of 1.1, with a follow-up period of 5 to 180 days. Histology
      showed a well endothelialised neointima (82 +/- 1% in high dose DES vs. 93 +/- 8%
      in BMS) already at five days, without differences in eNOS expression. Morphometry
      indicated that neointimal thickness in DES was significantly reduced as compared
      to BMS and Pol at 28 and 90 days. Polymer degradation products induced a distinct
      inflammatory response which was effectively suppressed in DES. Between 90 and 180
      days, however, the slow degrading low-dose stent showed catch-up of NIT.
      CONCLUSIONS: Tacrolimus eluted from a biodegradable stent coating can suppress
      the inflammatory effect of the coating degradation products if the balance
      between the drug levels and the degradation products is favorable.

PMID- 19112792
TI  - Percutaneous aortic valve implantation utilising a novel tissue valve:
      preclinical experience.

PMID- 19112793
TI  - Development of IMRISCardio, an integrated, interventional angio-MR imaging suite.

PMID- 19112794
TI  - Medical positioning system: a technical report.

PMID- 19112796
TI  - Natural look in volume restoration.
AB  - Filling and volumizing injection procedures are currently widely used for facial
      augmentation and re-establishing a youthful appearance. Aesthetic physicians have
      advanced from the practice of treating single lines and wrinkles towards filling
      large facial areas to globally restore natural facial contours and meet patient
      demand for nonsurgical rejuvenation. This review describes the different
      categories of fillers and volumizers based on their duration of action and
      ability to create a natural looking effect; they can be broadly classified as
      temporary or long-lasting biodegradable agents, or permanent nonbiodegradable
      agents. Temporary fillers are effective to correct lines and wrinkles, but may
      not adequately meet the need for global facial rejuvenation and volume
      replacement in a long-term, cost-efficient manner. Permanent fillers for global
      restoration pose the issue of long-term safety, and may not be compatible with
      changes in facial architecture with continued aging. Longer lasting volumizers
      provide patients with a durable, effective option for the restoration of facial
      volume and the re-establishment of youthful facial contours. Temporary fillers
      and volumizers may also be used in combination to provide a wide source of
      options for the global restoration and rejuvenation of the face.

PMID- 19112795
TI  - HBOC-201: the multi-purpose oxygen therapeutic.
AB  - Clinical and preclinical studies have revealed a diverse array of indications in
      which the effectiveness of HBOC-201 has been demonstrated or appears likely.
      Included among these are indications involving cardiac and peripheral ischaemia
      in which this oxygen therapeutic may prove to be an important tool in the
      armamentarium of the cardiologist and surgeon. Preclinical studies and clinical
      trials are under way to further delineate and optimise the role of HBOC-201 as an
      oxygen therapeutic in cardiovascular medicine.

PMID- 19112797
TI  - Complications of soft tissue augmentation.
AB  - The wide variety of dermal fillers presently available has revolutionized
      treatment options for patients seeking a refreshed appearance. Soft tissue
      fillers include both bovine and human collagens, the hyaluronans, calcium
      hydroxyapatite, poly-L-lactic acid, and synthetic polymers. However, soft tissue
      augmentation is never risk-free, and as these procedures have increased in
      prevalence, complications have been more frequently reported. This article
      describes a range of complications resulting from dermal filler injections,
      reviews key case studies, and discusses possible treatment options for adverse
      effects. While biodegradable fillers offer the least risk for the patient,
      location, allergic reactions, granulomas, necrosis, and infection are all serious
      complications that must be considered before performing soft tissue augmentation
      with any approved dermal filler.

PMID- 19112798
TI  - Use of intradermal botulinum toxin to reduce sebum production and facial pore
      size.
AB  - OBJECTIVE: Review the safety profile and subjective efficacy of intradermal
      botulinum toxin type A in facial pore size and sebum production. DESIGN:
      Retrospective analysis of 20 patients. RESULTS: Twenty consecutive patients with
      a single application of intradermal botulinum toxin type A were examined:
      Patients (17/20) noted an improvement in sebum production and a decrease in pores
      size at 1 month after injection. No complications were observed, and 17/20
      patients were satisfied with the procedure. CONCLUSION: Preliminary data suggests
      that intradermal botulinum toxin may play a role in decreasing sebum production.
      Further quantitive study may be necessary to determine effects of intradermal
      botulinum toxin on pore size.

PMID- 19112799
TI  - Modified Welsh regimen: a promising therapy for actinomycetoma.
AB  - BACKGROUND: Mycetoma has a worldwide geographical distribution which is extremely
      uneven; however, it is a common disease in India and responsible for causing
      significant morbidity. Treatment of this condition is often a challenge for the
      treating dermatologist. The authors report a promising therapy for patients of
      actinomycotic mycetoma. METHODS: This assessment series included 18 patients with
      a confirmed diagnosis of actinomycetoma, and who had shown a poor response to
      previous treatments. Patient received a combination therapy of the Welsh regimen
      (amikacin along with cotrimoxazole) to which rifampicin was added as a third
      drug. Clinical evaluation included radiology and laboratory investigations.
      RESULTS: Sixteen patients out of 18 completed the combination therapy, which lead
      to remission. Two patients were lost to follow-up. Of the 16 patients in
      remission, no recurrence was observed during a follow-up period of up to 18
      months.

PMID- 19112800
TI  - The safety and efficacy of fractional photothermolysis for the correction of
      striae distensae.
AB  - BACKGROUND: Improving the appearance of striae distensae, particularly striae
      alba, has remained a challenge due to the limited availability of effective and
      low-risk treatment options. Fractional photothermolysis, a novel concept in skin
      rejuvenation, has been reported to be effective in the treatment of facial
      rhytides, acne scars, and surgical scars, but its use in the treatment of striae
      has not been well studied. OBJECTIVE: To determine the safety and efficacy of
      fractional photothermolysis treatment on striae alba and striae rubra. METHODS:
      Twenty female patients with striae rubra or striae alba on their abdomen, thighs,
      or buttocks were enrolled in the study. Lesions were randomized to receive
      treatment, with site-matched normal control areas. Patients received a total of 6
      treatments using a 1550-nm, erbium-doped fiber laser with 2 to 3 weeks of elapsed
      time between treatments. Clinical response to treatment was assessed at each
      visit, and at 1-month, 2-month, and 3-month follow-up intervals by the patient
      and investigator. A comparison evaluation of 8 patients examining photographs of
      striae at baseline and at the 3-month follow-up evaluation which was assessed by
      4 independent dermatologists using the quartile grading scale. RESULTS: The
      independent evaluators' assessments of improvement from photographs of 8 randomly
      selected patients showed an overall improvement of 26% to 50% in 63% (5/8) of
      patients. A less than 25% improvement in dyschromia was noted in 50% (4/8) of
      patients. An improvement in texture of 26% to 50% was observed in 50% (4/8) of
      patients. The clinical responses were independent of age, gender, and skin
      phototype. The treatments were tolerated well by all patients with a majority of
      patients experiencing transient posttreatment erythema and edema. CONCLUSION:
      Fractional photothermolysis can be effectively and safely used in the treatment
      of striae rubra and striae alba.

PMID- 19112801
TI  - Reduction in facial photodamage by a topical growth factor product.
AB  - A topical gel containing a proprietary mixture of over 110 growth factors,
      cytokines, and soluble matrix proteins secreted by human dermal fibroblasts was
      evaluated for safety and efficacy in the treatment of mild to severe facial
      photodamage. In a double-blind study, 60 subjects were randomly assigned to
      receive either active gel or the vehicle and applied twice daily for 6 months
      along with a moisturizing cleanser and sunscreen. Efficacy (profilometry,
      photography, and clinical assessment) and safety (adverse event reporting)
      measures were evaluated at 0, 3, and 6 months. Treatment with the active gel for
      3 months produced greater reduction in fine lines and wrinkles than the vehicle
      treatment as measured by objective and subjective assessment techniques. The
      results were either statistically significant (P < or = .05) or trending towards
      statistical significance (P < or = .1). This study demonstrates that addition of
      a topical formulation of growth factors and cytokines to a basic skin care
      regimen reduces the signs of photoaging.

PMID- 19112803
TI  - Recurrent basal cell carcinoma discovered using positron emission tomography
      (PET) scanning.
AB  - A lesion detected on a positron emission tomography/computerized tomography
      (PET/CT) scan localized to the skin and was determined to be a large, recurrent
      basal cell carcinoma. This case demonstrates the ability of PET scans to detect
      recurrent, nonmelanoma skin cancers. It also serves as one example to
      dermatologists of how to manage incidental findings localizing to the skin.
      Finally, a discussion of expanding the use of PET scans in dermatology is
      considered.

PMID- 19112802
TI  - Analytic quantification of the bleaching effect of a 4-hydroxyanisole-tretinoin
      combination on actinic lentigines.
AB  - BACKGROUND: Solar lentigines represent a common feature of photoaging,
      particularly on the back of the hands. Bleaching agents are usually proposed to
      lighten the shade of the lesions. METHODS: The study was randomized and designed
      to assess the effect of a bleaching solution containing 2% mequinol (4
      hydroxyanisole, 4HA) and 0.01% tretinoin (Solage). The formulation was applied
      twice daily for 3 months on solar lentigines present on the back of one hand. The
      lesions on the other hand were treated with the ethyl alcohol vehicle which
      served as a control. Clinical diagnosis was confirmed using dermoscopy. In
      addition, objective measurements of the hypermelanosis were performed at 1-month
      intervals during and after treatment. Clinical assessments were used as well as
      narrow-band reflectance spectrophotometry, image analysis of video-recorded
      ultraviolet light-enhanced visualization (ULEV method) and photodensitometry of
      the corneomelametry test. RESULTS: The multipronged assessment of the lesional
      color demonstrated a significant lightening effect of the 4HA/tretinoin solution.
      This was demonstrated after 2 months of treatment and was maintained at least 2
      months after stopping treatment. CONCLUSION: Both the visual ratings and the
      objective bioinstrumental methods indicate the rapid lightening effect of the
      4HA/tretinoin formulation. After stopping treatment, the rate of repigmentation
      appeared to have slowed compared to the depigmentation phase.

PMID- 19112804
TI  - Association of angiokeratoma of the vulva with angioma serpiginosum.
AB  - Angioma serpiginosum is a rare benign vascular disorder usually beginning in
      childhood. It is characterized clinically by multiple minute, bright red to
      purple, grouped macules and histopathologically by an ectatic dilatation of
      capillaries. Angiokeratoma of the vulva is an uncommon lesion occurring in older
      women. It consists of purple papular lesions measuring less than 1 cm in diameter
      and characterizing histopathologically by hyperkeratosis, papillomatosis,
      acanthosis, and dilated vasculature in the papillary dermis.

PMID- 19112805
TI  - Porcine filler for facial lipoatrophy associated with human immunodeficiency
      virus treatment.
AB  - BACKGROUND: Facial lipoatrophy is a common problem for patients with human
      immunodeficiency virus (HIV) treated with highly active antiretroviral therapy
      (HAART). The loss of subcutaneous facial tissue occurs in the cheeks, temples,
      and periocular region. Facial lipoatrophy is a stigmatizing feature of HIV. The
      effective treatment can provide psychosocial stress for the patient. OBJECTIVE:
      To report on the experience using a novel porcine collagen filler in the
      treatment of a patient with HIV-associated facial lipoatrophy. Physician
      observations and photographs for documentation were collected up to 14 months
      posttreatment. METHODS: A patient with HIV with facial lipoatrophy was treated
      with a novel collagen injectable filler derived from porcine collagen. RESULTS:
      After 4 treatment sessions over 7 months using the novel porcine collagen
      injectable filler, significant improvement was found and dermal thickening was
      retained in the area of the cheeks for an additional 7 months. CONCLUSION: As
      facial lipoatrophy is a very stigmatizing manifestation of HIV, volume
      augmentation is highly beneficial. Using a novel porcine collagen, a natural
      outcome was obtained that lasted for over 4 months. Additional studies should be
      conducted to further investigate the use of a novel porcine collagen in the
      treatment of HIV-associated facial lipoatrophy.

PMID- 19112806
TI  - Effective use of topical amitriptyline hydrochloride 2.5% and ketamine
      hydrochloride 0.5% for analgesia in refractory proctodynia.
AB  - Idiopathic proctodynia, an enigmatic pain syndrome affecting the perianal region,
      can be persistent, relatively refractory to treatment, and associated with
      considerable psychological distress. The authors present the case of a patient
      with a long history of severe proctodynia that had been resistant to a range of
      topical and systemic treatments. With the use of topical amitriptyline
      hydrochloride 2.5% and ketamine hydrochloride 0.5% cream, the patient's pain
      resolved rapidly, leading to a substantially improved quality of life.

PMID- 19112807
TI  - Cutaneous drug eruptions induced by sorafenib: a case series.
AB  - Sorafenib, an epidermal growth factor receptor inhibitor, is a novel treatment
      used for malignancies resistant to traditional chemotherapy. Epidermal growth
      factor receptors (EGFR) are a family of 4 transmembrane tyrosine kinase receptors
      that, via signal transduction pathways, mediate cell growth, differentiation, and
      survival. Sorafenib is a targeted drug specifically engineered to inhibit Raf
      serine/threonine kinases, which are part of the reticular activating system (RAS)
      oncogene pathway. In addition, in vitro studies have shown sorafenib to be a
      potent multikinase inhibitor, targeting receptor tyrosine kinases associated with
      tumor angiogenesis (VEGFR-2, VEGFR-3, and PDGFR-beta) and progression. Initially,
      approved for use in advanced renal cell carcinoma, sorafenib is being studied for
      the treatment of other solid tumors at our institution. During the clinical
      trial, 4 patients were referred to the dermatology clinic for evaluation and
      treatment of diffuse erythematous eruptions all occurring 8 to 10 days after
      initiating sorafenib at a dose of 400 mg twice daily. These eruptions occurred in
      demographically similar patients and displayed similar clinical characteristics
      and histopathological findings. Clinically, 3 of 4 patients had facial erythema,
      3 of 4 had generalized macular erythema, 3 of 4 had widespread follicular-based
      papular eruption, and 4 of 4 had palmoplantar erythrodysesthesia. Half of the
      patients had cutaneous eruptions without systemic effects, while the other half
      had hypersensitivity reactions requiring withdrawal from clinical trial. This is
      the first case series illustrating drug eruptions induced by sorafenib.

PMID- 19112808
TI  - Interstitial granulomatous dermatitis associated with darifenacin.
AB  - Interstitial granulomatous dermatitis is most commonly associated with rheumatoid
      arthritis (RA) but may be induced by medications as well. Darifenacin is a
      muscarinic antagonist which was FDA approved for the treatment of overactive
      bladder in December 2004. The authors describe a case of interstitial
      granulomatous dermatitis associated with darifenacin.

PMID- 19112809
TI  - Azithromycin as an alternative rosacea therapy when tetracyclines prove
      problematic.

PMID- 19112810
TI  - Rethinking squamous cell carcinoma: which are high risk, which could benefit from
      lymph node dissection, what's coming up in the future?
AB  - Cutaneous squamous cell carcinomas (SCCs) are common skin cancers capable of
      metastasis. Determining which invasive SCCs are likely to recur or metastasize
      will help shape recommendations for clinical management. New prospective studies
      help predict which patients are at the highest risk for occult metastases and may
      benefit from lymph node dissection. In particular, the role of tumor depth,
      desmoplasia, and degree of immunosuppression could be accounted for in a more
      specific classification system. Evidence from studies of mucosal SCCs suggests a
      role for sentinel lymph node biopsies for carcinomas of the head and neck in
      place of selective neck dissection, a finding that may be relevant to cutaneous
      head and neck cancers as well. In the field of SCC pathogenesis, the role of
      human papillomavirus (HPV) in cutaneous, as well as mucous membrane, SCCs is
      being further characterized. For high-risk patients with iatrogenic
      immunosuppression, intense surveillance and early intervention is needed.

PMID- 19112811
TI  - Venous thromboembolism in hospitalized patients--are we doing enough to prevent
      it? Commentary to the ENDORSE trial.

PMID- 19112812
TI  - European guidance for the diagnosis and management of osteoporosis in
      postmenopausal women--what is the current message for clinical practice?

PMID- 19112813
TI  - Should all patients with chronic kidney disease take a statin? A commentary to a
      meta-analysis of randomized control trials.

PMID- 19112814
TI  - Hand hygiene in the intensive care unit: prospective observations of clinical
      practice.
AB  - INTRODUCTION: Adherence to hand hygiene recommendations in the intensive care
      unit (ICU) is variable and moderate, at best. OBJECTIVES: To measure adherence to
      hand hygiene recommendations among ICU clinicians in a prospective observational
      study in 6 multidisciplinary ICUs among 4 hospitals. PATIENTS AND METHODS: We
      observed 115 clinicians (64 nurses, 21 respiratory therapists, 18 residents and
      12 physicians) during 1 patient encounter, each. Clinicians were unaware that
      they were under observation. We documented use of gloves, soap, and alcohol
      solution before and after patient encounters for purposes of physical examination
      or patient care. RESULTS: The rate of adherence to current recommendations was
      20% (95% CI 13.7-28.2). All 23 clinicians adhering to recommendations used gloves
      followed by washing with soap or alcohol solution. 57.4% (95% CI 48.3-66.0) of
      clinicians used some form of hand hygiene without fully adhering to
      recommendations, whereas 42.6% did not appear to attend to hand hygiene at all
      during observation. By univariate analysis, with nurses as the reference group,
      we found trends suggesting lowest adherence rates among residents (odds ratio
      [OR] 0.32, 95% CI 0.11-0.96) and intensivists (OR 0.46, 95% CI, 0.13-1.60), and
      highest adherence among respiratory therapists (OR 2.05, 95% CI 0.67-6.30). We
      also observed a center effect (p = 0.04). However, multivariate analysis showed
      no relationship of hand hygiene to clinician group (p = 0.06) nor ICU (p = 0.05).
      CONCLUSIONS: Multidisciplinary, multimethod approaches to improving hand hygiene
      are likely necessary to improve the modest adherence to hand hygiene that we
      observed.

PMID- 19112815
TI  - Mortality and causes of death in HIV-positive patients receiving antiretroviral
      therapy at Tshepang Clinic in Doctor George Mukhari Hospital.
AB  - INTRODUCTION: Since the initiation of regular antiretroviral therapy and highly
      active antiretroviral therapy (HAART) in South Africa in 2004, data on effects of
      HAART on mortality are not available in our hospital. OBJECTIVES: We sought to
      describe mortality trends and causes of deaths among HIV-infected patients in the
      HAART era. PATIENTS AND METHODS: Consecutive HIV-infected adults who were
      prescribed HAART in our hospital were prospectively followed-up from July 2004 to
      December 2006 or until death, loss to follow-up, discontinuation of HAART or
      referral to another center. RESULTS: Out of 2605 HIV-infected patients analyzed
      at the end of 2006, 7.8% (n = 205) died. The causes of these 205 deaths were
      dominated by AIDS related disorders such as opportunistic infection (47.6%) and
      advanced AIDS status (37.3%). Non-AIDS infectious diseases, liver diseases,
      cardiovascular diseases, and cancers were rare. Mortality rate was higher in
      males (28%, p < 0.0001) than females (8%) as well as in subgroup with CD4 cell
      counts < 200/microl (8%, p < 0.0001) than in subgroup with CD4 cell counts >
      200/microl (4.9%). There was a negative significant dose - response relationship
      (p for linear trend < 0.0001) between mortality and baseline CD4 cell counts
      among patients with CD4 cell counts < 200/microl, 13% in the CD4 < 50/microl
      group, 6% in the CD4 51-100/microl group, 5.5% in the CD4101-150/microl group,
      and 3% in the CD4 > 151/microl group. Mortality was not associated with age and
      HAART regimens. CONCLUSIONS: Prevention of AIDS-defining conditions and expansion
      of earlier access to HAART could substantially reduce mortality in resource-poor
      settings.

PMID- 19112816
TI  - Venous thromboembolism risk and prophylaxis in the acute hospital care setting-
      results of the ENDORSE study in Poland.
AB  - INTRODUCTION: Venous thromboembolism (VTE) is the most common preventable cause
      of in-hospital death. However, the risk of VTE and prophylaxis practices in
      Polish hospitals are not known. OBJECTIVES: The ENDORSE study in Poland was part
      of the global cross-sectional Epidemiologic International Day for the Evaluation
      of Patients at Risk for Venous Thromboembolism in the Acute Hospital Care Setting
      survey with the objective to assess the prevalence of VTE risk in acutely ill
      medical and surgical patients and to determine the proportion of at-risk patients
      who receive recommended prophylaxis. PATIENTS AND METHODS: In 10 non-academic
      Polish hospitals, a chart review was performed in all inpatients aged 40 or older
      admitted to medical wards, and in patients at the age of > or = 18 admitted to
      surgical wards. The VTE risk and recommended prophylaxis were assessed according
      to the 2004 American College of Chest Physicians (ACCP) guidelines. RESULTS: The
      study enrolled 2673 patients (1092 in surgical wards, 1581 in medical wards). Out
      of these, 1111 were judged to be at risk for VTE (597 surgical patients, 514
      medical patients). Only 51.8% of all at-risk patients received ACCP-recommended
      VTE prophylaxis (54.7% of surgical patients, 32.5% of medical patients).
      CONCLUSIONS: In Polish hospitals more than 40% of patients hospitalized for acute
      illness are at risk of VTE, but only a small proportion of them receives
      appropriate prophylaxis. These results call for decisive actions to ensure that
      at-risk patients receive recommended VTE prophylaxis.

PMID- 19112817
TI  - Diagnosis and the current trends in multiple myeloma therapy.
AB  - Multiple myeloma is still an incurable disease. In recent years the introduction
      of 3 novel drugs oriented on basic mechanisms of multiple myeloma cells
      proliferation and survival has improved patients' outcome. These drugs are:
      thalidomide, its new analog, lenalidomide, and proteasome inhibitor, bortezomib.
      All three are highly effective both in newly diagnosed and relapsed/resistant
      patients.

PMID- 19112818
TI  - Primary idiopathic glomerulonephritis: modern algorithm for diagnosis and
      treatment.
AB  - In most countries glomerulonephritis is the second most common cause of the end
      stage renal disease, after diabetic nephropathy in renal replacement therapy
      programs. Occurence of primary glomerular diseases in young and middle aged
      patients, in whom they restrain their lives and professional careers, results in
      their particular position among causes of replacement therapy. A highly important
      component of the therapeutic approach to nephrotic patients is appropriate
      symptomatic treatment. Proteinuria reduction is crucial in the prevention of
      progressive kidney function decline in the course of glomerulonephritis. A long
      term therapy of glomerulonephritis should be conducted both by the general
      internal medicine specialist and the nephrologist. The treatment with angiotensin
      converting enzyme inhibitors and angiotensin receptor blockers can be performed
      by the internist, but the immunosuppressive programs should be initiated and
      supervised by the nephrologist.

PMID- 19112819
TI  - Chronic heart failure in the elderly: a current medical problem.
AB  - As a result of population ageing and improved medical care that contribute to
      better life expectancy, heart failure occurs more and more commonly in the
      elderly. In the USA approximately 80% of patients discharged from hospital with
      newly diagnosed heart failure are over 65 years of age, whereas 50% are over 75.
      The average 5-year mortality rate is about 50% in subjects with systolic
      dysfunction and similar in those with preserved left ventricular systolic
      function. Disorders of the cardiovascular system occurring in the elderly (e.g.
      increased left ventricular mass, myocardial rigidity, atrial fibrillation,
      decreased maximum oxygen uptake in cardiopulmonary exercise tests) result from
      the physiological ageing; they may also be caused by a concomitant cardiac
      failure syndrome. In the elderly, heart failure is often accompanied by
      concomitant conditions that often make diagnosis and treatment of chronic heart
      disease difficult. Non-specific clinical symptoms in the elderly as well as those
      associated with age (e.g. easy fatigability, exertional dyspnea) make a correct
      diagnosis difficult. The recognized biochemical marker of heart failure--brain
      natriuretic peptide, N-terminal pro-brain natriuretic peptide--has a limited
      diagnostic value in the elderly. Echocardiography plays a key role in the
      diagnosis. Owing to altered metabolism, impairment of hepatic processes to
      various degrees and decreased renal excretion of drugs, treatment requires
      attention, individual choice of drugs and doses, as well as periodic modification
      of both the doses and the intervals between them. Correct treatment improves
      quality of life and prolongs it. The aim of the present work is to present the
      differences in the pathophysiology, diagnostic evaluation and management of
      chronic heart failure in the elderly, in light of the current views and
      standards.

PMID- 19112820
TI  - Actinomycosis mimicing advanced cancer.
AB  - Actinomycosis is a rare infectious inflammatory disease caused by the bacteria of
      the Actinomyces species. Infection occurs following damage to the skin or mucous
      membrane. This report presents a case of a 50-year-old female patient with
      subfebrile temperature, weight loss and pain, who used to have an intrauterine
      device. Masses suggestive of an advanced cancer were detected in her pelvis and
      abdominal cavity. A diagnosis of actinomycosis was made after histopathological
      examination of the tissue sample.

PMID- 19112821
TI  - A 21-year-old female patient with Peutz-Jeghers syndrome.
AB  - The paper describes a case of a 21-year-old woman admitted to the Department of
      Internal Medicine with signs and symptoms of microcytic anemia. The presence of
      characteristic skin lesions, results of laboratory tests and positive family
      history led to the diagnosis of a rare colonic polyposis, Peutz-Jeghers syndrome.
      The article presents also history, symptomatology, recommended tests and
      treatment of Peutz-Jeghers syndrome. Particular attention has been paid to
      necessity of periodic endoscopic investigations of the gastrointestinal tract
      with concurrent polyp resection.

PMID- 19112822
TI  - [Role of SUMO modification in the maintenance of genome stability].
AB  - SUMO modification (SUMOylation) is a postranslational modification playing an
      important role in chromatin structure, DNA metabolism, transcriptional regulation
      and genomic stability. Molecular mechanisms underlying such effects of SUMO
      modified proteins are largely obscure, but the influence of SUMOylation on
      genomic stability seems to be of particular importance since its disturbances may
      lead to serious pathological states, including cancer. Cell cycle control and DNA
      repair proteins essential for preserving genomic stability and SUMO modification
      may change their localization and function. We have relatively much information
      on some subnuclear components, like nucleous, while little is known on some
      others, like PML bodies, but the results of some recent research suggest, that
      this is SUMOylation, which plays a key role in their architecture and
      functioning. The influence of SUMO modifications on genomic stability and
      chromatin structure may be fundamental for cell's viability, therefore the
      mechanisms of SUMOylation are worth studying.

PMID- 19112823
TI  - [Regulation of gene expression by long-chain fatty acids].
AB  - Besides of their role as important energy source and membrane component, long
      chain fatty acids also act as bioactive lipids involved in the regulation of such
      processes like cell proliferation and differentiation, protein acylation and
      sorting, inflammation, activation of enzymes and membrane receptors, and
      regulation of intracellular metabolism. One of the mechanisms by which fatty
      acids affect so many various biological processes is regulation of the gene
      transcription. Depending on the number of double bonds and carbon chain length,
      fatty acids may inhibit or activate expression of defined genes through either
      direct regulation of activity of nuclear receptors including PPAR, LXR and HNF-4
      alpha or transcription factors mainly SREBP, ChREBP and NF kappa B; or
      indirectly, through physicochemical changes in membrane properties and activation
      of signal transduction pathways. In this paper we review the current
      understanding of the mechanisms by which fatty acids regulate gene expression and
      discuss their role in the pathogenesis of metabolic disorders.

PMID- 19112824
TI  - [Structure and function of the eukaryotic ribosome].
AB  - The protein biosynthesis is a complicated process and not fully understood yet.
      According to smaller size and less complicated structure, understanding of
      prokaryotic 70S ribosomes is much more advanced. Eucaryotic 80S ribosomes are
      more complex and generate more difficulties in research. The morphology of 80S
      ribosome has been pretty well resolved and we know a lot about mechanism of
      functioning. Determination of the interactions between the ribosomes and the
      factors taking part in protein biosynthesis is still a great challenge. Dynamic
      changes of these interactions during particular steps of elongation cycle are
      quite difficult to understand. Conformational changes of the ribosome are of
      great functional and regulatory importance during protein biosynthesis. They are
      essential for the whole gene expression process. Only further research of the
      structure and function of the ribosome will lead us to knowledge about
      specificity of the mechanism of their action. In this article we present current
      opinions concerning structure and function of the eukaryotic ribosomes.

PMID- 19112825
TI  - [TGF beta signalling accessory receptors].
AB  - TGF beta signalling pathways apart from receptors, their ligands and
      intracellular effectors consist of proteins capable to bind ligands which are not
      classical receptors. They do not transmit the signal directly into the cell but
      by their interaction with TGF beta family factors and TGF beta type I and II
      receptors can influence TGF beta cascade activity. There are three proteins
      characterised by such features i.e., betaglycan (TGF beta RIII), endoglin (CD105)
      and antigen CD109 which are commonly called as TGF beta accessory/auxiliary
      receptors or TGF beta type III receptors. Their key function is to modulate
      accessibility of ligands to TGF beta type I and II receptors. The role of TGF
      beta accessory receptors has been well documented for signal transduction via TGF
      beta isoforms--TGF beta 1, TGF beta 2 and TGF beta 3. Each TGF beta accessory
      receptor has different TGF beta isoforms binding specificity and cellular
      response character. TGF beta cascade is the only known cellular signalling
      pathway for which accessory receptors are identified until now.

PMID- 19112826
TI  - [Creatine kinase isoenzymes--characterization and functions in cell].
AB  - Creatine kinase (CK, EC 2.7.3.2) is a key enzyme of cellular bioenergetics. The
      tissue-specific distribution, subcellular localization and function of CK
      isoenzymes in tissues and cells with high energy requirements, as well as the
      molecular structure of mitochondrial CK, point to an important physiological role
      of CK system for cellular energetics. The extensive studies about properties of
      mitochondrial creatine kinase isoforms gave a new perspective to create a
      functional model of CK isoforms action called "phosphocreatine shuttle". In this
      model the CK isoforms together with easily diffusible compounds like creatine and
      phosphocreatine, maintain a cellular energy buffer and intracellular energy
      transport system, where the "high-energy" phosphate is transferred between site
      of ATP synthesis and site of ATP utilization. Mt-CK octamer is able to bridge two
      mitochondrial membranes and interacts functionally with porin VDAC and ANT in
      cardiolipin vicinity. Mt-CK with its substrates also activates oxidative
      phosphorylation and effectively inhibits formation of mitochondrial permeability
      transition pore. Any destabilization of octamer structure would induce an
      apoptosis process.

PMID- 19112827
TI  - [The role of ABC transporters in the renal elimination of organic anions and
      drugs].
AB  - The ATP-binding cassette (ABC) transporters are a large superfamily of integral
      membrane proteins that actively transport organic ions across biological
      membranes. These transporters play important role in the reabsorptive and
      excretory capacity of the kidney. Nine structurally and functionally related
      members (MRP1-7, P-gp, BCRP) have been identified, which differ from each other
      by their localization, expression levels, and substrate specificity. This review
      discusses current knowledge on the renal characteristics of ABC transporters,
      with specific focus on their regulation.

PMID- 19112828
TI  - [The involvement of the renin-angiotensin system (RAS) in cancerogenesis].
AB  - The family of angiotensin peptides was connected mainly with cardiovascular
      system and water-electrolic balance. During the last decade it has been
      established that, apart from its classical actions, Ang II is involved in the
      regulation of cell growth, proliferation, cell migration, apoptosis,
      inflammation, differentiation, angiogenesis and gene expression, which suggests
      that this peptide might also play role in a cancer. This review focuses on the
      role of the RAS in tumors and present clinical potential of manipulating the
      angiotensin system as a novel and promising strategy for cancer treatment.

PMID- 19112829
TI  - [Reverse cholesterol transport processes and their role in artherosclerosis
      regression].
AB  - Atherosclerosis represents dynamic process with periodic tendency to reverse.
      Although animal experiments and human studies have provided considerable evidence
      of atherosclerosis regression, our understanding of this phenomenon remains still
      incomplete. Atherosclerosis regression depends on removal of cholesterol deposits
      from atherosclerotic plague in the process of reverse cholesterol transport and
      possibly other mechanisms including migration of macrophages and foam cells,
      inhibition of inflammation and endothelial regeneration. Our paper reviews
      available data on the process of atherosclerosis regression with special
      attention to the reverse cholesterol transport.

PMID- 19112830
TI  - [Plant micro RNA biogenesis].
AB  - Micro RNAs are 21-24 nt long RNA molecules involved in the regulation of gene
      expression on mRNA level. Mature miRNA molecules associated with the RNA-induced
      silencing complex (RISC) guide specifically mRNA cleavage or inhibit the
      translation. In plants selective mRNA degradation in miRNA-dependent pathway is a
      widespread mechanism that occurs more frequently than translation inhibition.
      miRNA precursors, known as pri-miRNA, are processed in several steps to produce
      mature miRNA molecules. There are several plant proteins involved in miRNA
      processing: DCL1, HYL1, SE, HEN1 and HASTY. The role of these proteins is
      discussed.

PMID- 19112831
TI  - [The extracytoplasmic protein quality control in bacterium Escherichia coli; the
      role of proteases and the folding factors].
AB  - The proper functioning of extracytoplasmic proteins requires their correct
      folding after translocation and reaching a proper destination within the cellular
      envelope. This process is supervised by the folding factors and proteases, which
      comprise the protein quality control system. The coordinated action of its
      components maintains the proper functioning of the cell under physiological
      conditions and enables the survival of bacteria under stress conditions. In the
      present work we provide the concise characteristics of the protein quality
      control system within the cellular envelope with the particular emphasize on the
      role of proteolysis in maintaining the cellular homeostasis.

PMID- 19112832
TI  - [Oxidative stress in cerebral stroke].
AB  - Free radicals are molecules or ions containing non-paired electrons on the
      external orbit, which ensures their high chemical activity. In systemic
      homeostasis, free radicals are inactivated by endo- and exogenous antioxidants
      and do not have destructive effects. The human organism possesses protective
      mechanisms, i.e. enzymatic systems (peroxide dismutase, glutathione peroxidase,
      catalase) and non-enzymatic systems (vitamin C and E selenium, coenzyme Q, lipoid
      acid, bilirubin). Imbalance between continuous production of reactive oxygen
      forms and their elimination due to enzymatic and non-enzymatic neutralization
      reactions as well as effects of exogenous antioxidants is defined as oxidative
      stress. Recent studies demonstrated a significant role of inflammatory processes
      and oxidative stress in the pathomechanism of cerebral stroke. Increased
      production of free radicals was observed in both the ischaemic and haemorrhagic
      strokes and oxidative stress was shown to be one of the causative mechanisms of
      tissue damage in these diseases. This was confirmed by numerous studies assessing
      the concentration of oxidative stress biomarkers and levels of plasma
      antioxidants (enzymatic and non-enzymatic). At present, studies are being carried
      out about the use of antioxidative substances for the therapy of cerebral stroke.
      The present study reports current findings concerning oxidative stress issues in
      patients with stroke.

PMID- 19112833
TI  - [Genetic predisposition to systemic complications of arterial hypertension in
      maintenance haemodialysis patients].
AB  - Cardiovascular disease is the most common cause of a high morbidity and mortality
      in patients on renal replacement therapy and is responsible for about 50% of
      deaths. Hypertension is the main risk factor for cardiovascular events in the
      general population as well as in haemodialysed (HD) patients. The hypertension in
      HD patients is caused by excess extracellular fluid volume (ECV) on the other
      hand hypertension resistant to normalization of ECV may result from the
      accelerated activity of the systemic and local--vascular renin-angiotensin
      aldosteron system (RAAS). RAAS genes are potential etiological candidates for
      cardiovascular damage. The aim of the study was to evaluate the prevalence of
      hypertension, left ventricular hypertrophy, hypertensive retinopathy in patients
      treated with haemodialysis and to evaluate the association between the
      polymorphism of RAAS genes: ACE I/D, AGT M235T AT1R A1166C, CYP112 (-344) and the
      systemic complications of arterial hypertension such as hypertensive retinopathy,
      left ventricular hypertrophy and also mortality in haemodialysis patients.
      MATERIAL AND METHODS: The studied population consisted of 302 HD patients (175
      men, 127 women) age 21-87, mean 56, at four dialysis units. Patients with cardiac
      defect, advanced coronary artery disease and atrial fibrillation were excluded
      from the study. 62 patients died during 3,5 years of observation. Methods
      consisted of tree times repeated blood pressure measurements before and post
      dialysis, echocardiography, direct opthalmoscopy (Keith-Wegener-Barker
      classification of hypertensive retinopathy) and DNA analysis--genotypes ACE I/D,
      AGT M235T AT1R A1166C, CYP11B2 T(-344)C were determined through PCR or PCR-RFLP
      method. RESULTS: Hypertension was present in 72%, LVH in 84% haemodialysed
      patients. Arterial pressure correlated with LVMI values and hypertension was
      connected with LVH. Insufficient control of blood pressure and LVH were connected
      with worse survival in HD patients. CONCLUSIONS: It seems that I/D polymorphism
      ACE gene and AC AT1 gene influence the development of hypertension and LVH in HD
      patients. The most dangerous in the development of hypertension and LVH was DD
      genotype ACE gene and CC AT1 gene. ACE I/D, AGT M/T, AT1 A/C, CYP11B2 T/C
      polymorphism appears to have no relation to the short-term prognosis in HD
      patients. The mortality did not differ among groups with different genotypes of
      ACE I/D, AGT M/T AT1 A/C, CYP11B2 T/C polymorphisms. Direct ophtalmoscopy seems
      to be an insufficient method in the estimation of the systemic complications of
      hypertension in haemodialysed patients.

PMID- 19112834
TI  - [The clinical manifestation of duodeno-gastroesophageal reflux (DGER) in the
      children and adolescents].
AB  - The development of the new techniques and methods enabled to investigate the role
      of duodenal reflux in the pathogenesis of gastroesophageal reflux disease (GERD)
      therefore there is a need to establish the most common symptoms occurring in
      patients with duodenal reflux. THE AIM OF THE STUDY: To determinate the type of
      manifestation and the prevalence of duodeno-gastroesophageal reflux in children
      and adolescents confirmed in Bilitec 2000 method. MATERIALS AND METHODS: 59
      patients (37 girls, 22 boys) aged 7-17 years (mean 14.7) with the symptoms of GER
      there were divided into 2 groups: subgroups: A--18 children with confirmed
      duodeno-gastroesophageal reflux in Bilitec 2000TM method and B--control consisted
      of 15 children with short stature referred to endoscopy due to celiac disease
      exclusion. In accordance to the endoscopic finding there were selected 3
      subgroups: 20 patients with duodenal reflux, 19 patients with esophagitis and 20
      children presenting those both disorders simultaneously. In all patients from
      group B the endoscopy, Bilitec 2000 and esophagitis pH metric findings haven't
      showed any abnormality. RESULTS: The most common complain--in 16 (88.89%)
      patients was recurrent and/or chronic abdominal pain, next- heartburn in 12
      (66.67%), vomits and/or regurgitations in 10 (55.56%) children. CONCLUSIONS: The
      clinical manifestation of duodenal reflux was very much alike as in acid
      gastroeophageal reflux in the examined group. Therefore the functional
      gastrointestinal tract examinations have to be included in the diagnostic
      procedure.

PMID- 19112835
TI  - [Gastric complaints or postcholecystectomy syndrome?].
AB  - Postcholecystectomy syndrome (PCS) is a complex of symptoms from gastrointestinal
      tract that could develop and maintain after cholecystectomy. PCS usually consists
      of: abdominal pain or colic, dyspepsia, constipation or diarrhoea, nausea,
      bloating, fatty food intolerance. Regarding PSC as disease entity is still a
      point of many controversies. THE AIM OF THE STUDY: To estimate the prevalence of
      PCS in patients after cholecystectomy performed in Department of General and
      Colorectal Surgery of Medical University in Lodz. Material and methods. From the
      cohort of 243 patients (pts) operated on due to symptomatic cholecystitis the
      group of 150 pts was surveyed. We included 86 pts who answered the questionnaire.
      The prevalence of PCS and intensity of symptoms were measured with the use of
      modified Gastrointestinal Symptoms Rating Scale (GSRS)--only 6 complaints
      commonly connected with pathology of biliary system were chosen (abdominal pain,
      rebounding, constipation, urgent diarrhea, nausea, bloating). RESULTS: After
      cholecystectomy gastric complains were revealed in 32 pts (37.2%). In a group of
      12 pts (13.9%) symptoms were noted at the same level of intense. However in 20
      pts (23.25%) either more intense or appeared as brand new manifestation.
      Excessive amount of intestinal gases (93.75%) and bloating (87.5%) were the most
      common symptoms unlike abdominal pain, heartburn and diarrhea. CONCLUSIONS:
      Gastric symptoms of PCS occur in one third of pts after elective
      cholecystectomies. Complete PCS develops after 3 months postoperatively what is
      likely connected with the change of diet. Excessive amount of intestinal gases,
      bloating, abdominal pain and diarrhea were the most common symptoms. The most
      intense complaint is persistent abdominal pain likely indicating comorbidities.

PMID- 19112836
TI  - [Attention abnormalities in patients with chronic hepatitis C after pegylated
      interferon alpha and ribavirin treatment].
AB  - THE AIM OF THE STUDY: To (a) describe the influence of peg-IFNalpha 2a and 2b on
      attention processes and (b) to assess whether attention abnormalities induced by
      peg-IFNalpha/RBW resolve 8 weeks after treatment discontinuation in chronic
      hepatitis C patients. MATERIAL AND METHODS: 26 chronic hepatitis C patients
      treated with peg-IFNalpha2a (n=18) or 2b (n=8) and RBV were enrolled in the
      study. Attention processes were tested three times: before the beginning (t=0),
      after 12 weeks of medication (t=1) and 8 weeks after treatment discontinuation
      (t=2). Attention was assessed with Brickenkamp d2 test and the results were
      compared in groups of patients treated with different kinds of peg-IFNalpha.
      RESULTS: The two kinds of peg-IFNalpha did not differ significantly regarding the
      influence on attention processes. 8 weeks after treatment discontinuation (t=2)
      there was observed a significant decrease all aspects of attention measured by d2
      test, i.e. work accuracy, speed of processing and ability to focus attention
      comparing with t=0 and t=1. CONCLUSIONS: Peg-IFNalpha/RBW therapy is connected
      with a decrease in attention processes performance and the two kinds of peg
      interferon alpha (2a and 2b) may exert a similar influence. Attention dysfunction
      did not resolve 8 weeks after treatment discontinuation and may be the
      irreversible effect of the dorso-lateral prefrontal cortex or anterior cingulate
      cortex damage.

PMID- 19112837
TI  - [The voice and speech quality in laryngectomy patients rehabilitated with second
      generation voice prosthesis].
AB  - Voice rehabilitation with the application of voice prostheses is a method of
      choice in surgical rehabilitation of patients following total laryngectomy. THE
      AIM OF THE STUDY: To compare voice quality and fistula speech with use of second
      generation voice prostheses to voice and esophageal speech in patients
      rehabilitated with vocal method. MATERIAL AND METHODS: The following study
      comprised 37 patients with fistula speech (group I). The assessment of voice
      quality included subjective and objective examination and acoustic analysis of
      fistula speech and aesophageal. Examination results were compared with data
      obtained in 15 patients with oesophageal voice of similar age and gender
      composition (group II). The acoustic analysis was performed using IRIS Medicom
      software. Fo values and Jitter, Shimmer, HNR parameters were analysed. RESULTS:
      All examined patients with fistula speech demonstrated a permanent capacity of
      speaking, which enabled efficient verbal communication. Average values obtained
      during 'perception test' located this type of phonation between good and very
      good speech. Formant recordings in narrow-band spectrographs indicated relatively
      normal supraglottal articulation which is a factor conditioning good speech
      comprehension. During subjective assessment, fistula voice and speech were
      moderately loud, dull, hoarse, uttered in unrestrained, breathed way rather than
      being forced. Persistence of the pathologic phonation was confirmed by acoustic
      voice evaluation parameters (Jitter, Shimmer, HNR and Fo). CONCLUSION:
      Examination findings confirm better voice quality obtained in rehabilitation with
      second generation voice prostheses as compared to oesophageal voice and speech
      resulting from natural rehabilitation process.

PMID- 19112838
TI  - [Analysis of voice disorders among university teachers at Medical University of
      Bialystok].
AB  - Voice disorders constitute a serious health problem for teachers. More than 80%
      of them experience voice disorders and still among those 40% suffer from
      pathological phoniatric changes confirmed by phoniatric examination. Chronic
      disorders resulting from vocal abuse and misuse are the most frequent among
      occupational diseases diagnosed in Poland. THE AIM OF THE STUDY: To investigate
      the chronic voice disorders among the teaching community of Medical University of
      Bialystok and to examine its awareness of voice hygiene and proper vocal
      techniques. MATERIAL AND METHOD: The research was based on a survey of 434
      university teachers from Medical University of Bialystok. Results. Increased
      voice fatigue and voice loss were most often the consequence of prolonged voice
      use (over 20 years). Occupational voice disorders were more frequent in females,
      even though they did not ignore initial symptoms and consulted specialists.
      Disregard for prevention, reluctance to undergo treatment, and negligence of the
      first symptoms of disease are the most common cause of occupational voice
      disorders. CONCLUSION: Working in a voice-friendly environment, organizing
      trainings devoted to voice hygiene and vocal techniques are in favor of enhancing
      the voice function of university teachers.

PMID- 19112839
TI  - [Islet isolation outcome is influenced by pancreas preparation method].
AB  - Pancreatic islet transplantation is a treatment method for type I diabetes. Its
      outcome is influenced by numerous factors, islet quantity and function being
      important ones of them. THE AIM OF THIS STUDY: was to estimate the influence of
      pancreas preparation method on the outcome of islet isolation in rat. MATERIAL
      AND METHODS: 6 pancreata harvested from Lewis rats were used in this research.
      Pancreatic duct was cannulated and pancreas was injected with 1 mg/ml collagenase
      P solution (Sigma) and then excised. After cutting into smaller fragments, it was
      digested in collagenase P solution for 15-20 min. Enzyme activity was then
      stopped by adding dilution medium. Heterogenous cell suspension was centrifuged
      in density gradient (Gradisol) to isolate islets. Pancreatic islets were
      collected and islet equivalent was calculated. Islet purity degree was estimated
      as islet cells to all cells, including exocrine, ratio. Islet viability was
      estimated using propidium iodide and fluorescein diacetate staining. Photographic
      documentation was made. RESULTS: Proper islet morphology, highest number and
      viability was obtained when pancreas was excised properly (isolation 3 and 4).
      CONCLUSION: Pancreas preparation method is one of which influences on islet
      isolation outcome.

PMID- 19112840
TI  - [Abandoning of breast cancer radical treatment--own observations].
AB  - Breast cancer is currently one of the most frequent cancers women in Poland
      suffer from. Incidence increases after 35 years of age and this rate remains high
      until the old age. Since the 1980s breast cancer has been the most frequent
      reason for deaths of women between 40 and 59 years of age. Breast cancer
      treatment is based on combination of surgical methods, the hormone therapy,
      chemiotherapy and radiotherapy. However treating the cause and palliative
      treatment may result in complications. Some patients do not give their consent to
      suggested medical treatment. The aim of this work is an attempt to stress
      complexity of breast cancer radical treatment, with patients suffering from
      breast cancer as an example.

PMID- 19112841
TI  - [Hyponatremia in syndrome of inappropiate antidiuretic hormone secretion--cases
      report].
AB  - Syndrome of Inappropriate Antidiuretic Hormone Secretion (SIADH) is a rare
      disease characterized by hyponatremia and hyperosmolality of urine. There are
      well known causes of this syndrome, such as neoplasmatic processes, different
      disorder of central nervous system, lung diseases and side effects various drugs.
      In differential diagnosis of this syndrome we ought to consider renal failure,
      adrenocortical deficiency (Addison's disease), hypothyroidism, different forms of
      hyponatremia as well as pseudohyponatremia.

PMID- 19112842
TI  - [Rehabilitation of voice at paralytic dysphonia--case report].
AB  - Paralytic dysphonia is a voice disorder created as a result of neurogenic injury
      of the neuromuscular larynx organ, owing to the laryngeal nerves paralysis or
      paresis. It is of the most serious voice producing larynx organ lesions. The
      paper presents the case of 53-year-old patient with a total neurogenic traumatic
      left vocal cord paralysis. The usefulness of an early phoniatric and logopedic
      rehabilitation by means of breathing and kinetic exercises, mechanotherapy and a
      vocalistic and phonetic method in order to obtain the improvement of the quality
      of voice in paralytic dysphonia was analysed. The complex subjective and
      objective foniatric assessment of the voice quality before and after the
      rehabilitation indicated the usefulness of applied methods and the improvement of
      all parameters of the voice quality in the analyzed case.

PMID- 19112843
TI  - [Re-infection with Borrelia burgdorferi s.l in a patient with a history of
      neuroborreliosis--case report].
AB  - Reinfection with Borrelia burgdorferi s.l., which is likely in highly exposed
      persons, has not been described in Poland so far. Symptoms of Lyme arthritis,
      preceded by typical skin lesion (erythema migrans) appeared in 46 years old women
      5 years after successful treatment of borrelial meningitis. Re-appearance of
      symptoms of Lyme borreliosis following localized skin lesion, after a long
      asymptomatic period, as well as accompanying increase in specific antibodies,
      point to reinfection with Borrelia burgdorferi sensu lato. Different localization
      of systemic symptoms during two episodes of Lyme disease suggests infection with
      distinct genospecies of B. burgdorferi s.l. This case confirms risk of recurrent
      infections with different B. burgdorferi s.l. genospecies in inhabitants of
      highly endemic areas in the north-east of Poland, which may pose necessity of
      repeated antibiotic treatment.

PMID- 19112844
TI  - [Reinfection in Lyme borreliosis].
AB  - Persons exposed to tick bites in endemic areas of Lyme borreliosis are at high
      risk of repeated infections with Borrelia burgdorferi s.l. Typically, recurrent
      episodes of Lyme borreliosis present as erythema migrans, but systemic
      manifestations, like borrelial arthritis and meningitis, have been described.
      Differentiating reinfection from relapse or chronic sequelae of primary infection
      should be possible on the basis of epidemiological data, clinical course and
      careful interpretation of serologic tests results. In case of reinfection,
      antibiotic treatment should be administered.

PMID- 19112845
TI  - [Role of endotoxin in pathomechanism of sepsis].
AB  - The nosocomial infections caused by Gram-negative bacteria, in this number
      Acinetobacter baumannii and Pseudomonas aeruginosa, have severe course and
      relatively high prevalence of sepsis cases. Pathomechanism of sepsis is related
      to activation and release of bacterial endotoxin, which is a macromolecule
      engaged in initiation of cytokine cascade. These mediators are responsible for
      heavy tissues and organs devastation. Factors that bind and neutralize endotoxin
      in organism are promising candidates for experimental therapy of sepsis.

PMID- 19112846
TI  - [Antioxidative enzymes--structure, properties, functions].
AB  - In physiological condition mammalian cells produce a small amount of reactive
      oxygen species (ROS) which influence biological processes. At high concentration
      ROS are the mediator of damage to lipids, protein and nucleic acids. Exposure to
      free radicals has led organisms to develop series of defense mechanism that can
      protect against oxidative stress. The defense mechanism is represented by non
      enzymatic antioxidants and enzymatic antioxidants that are mainly represented by:
      superoxide dismutases (SOD), catalase (CAT) and, glutathione peroxidases (GPx),
      glutathione reductase (GR). This article presents short review about structure,
      properties and functions of the above enzymes in living cells.

PMID- 19112847
TI  - [Chosen non-enzymatic substances that participate in a protection against
      overproduction of free radicals].
AB  - Free radicals are substantial elements that take part in proper function of
      metabolic pathways of human cells and tissues in hydrophobic as well as in
      hydrophilic environment. Nevertheless overproduction of above molecules causes
      oxidative stress, a process which is very harmful for lipids, proteins, and
      others molecules what reduces their normal function. To protect against adverse
      effects of free radicals and theirs derivatives to human body there is a group of
      antioxidants divided into enzymatic and non-enzymatic substances. Enzymatic
      antioxidants are represented mainly by enzymes such as: copper-zinc superoxide
      dismutase (CuZnSOD), catalase (CAT), glutathione peroxidase (GPx) and glutathione
      reductase (GR). Glutathione (GSH), thioredoxin (Trx), vitamins, melatonin,
      polyphenols, trace elements, albumin, and others function as non-enzymatic free
      radicals scavengers. This work in a brief way describes properties of chosen
      representants of non-enzymatic antioxidant system.

PMID- 19112848
TI  - [The effect of alcohol on the regulation of iron metabolism].
AB  - Chronic alcohol consumption increases body iron stores. Patients with alcoholic
      liver disease frequently exhibit iron overload, but mechanisms of its
      accumulation remain unclear. Many novel iron-regulatory proteins have been
      identified for several last years, which have improved understanding the
      underlying some mechanisms of iron overload in alcoholic liver disease. In this
      paper, the effect of alcohol on hepcidin expression which is a key hormone in the
      regulation of iron metabolism has been given. Hepcidin regulates of iron
      metabolism by inhibiting intestinal iron absorption and the release of iron from
      macrophages. Alcohol was found to down-regulate hepcidin expression in the liver
      leading to elevated expression of the iron transporter proteins, DMT1 and
      ferroportin in the duodenum. Ethanol-mediated oxidative stress inhibits C/EBPaz
      DNA-binding activity and down-regulates hepcidin transcription in the liver.
      Deregulation of the hormone synthesis may be one of the causes of iron overload
      during chronic alcohol consumption.

PMID- 19112849
TI  - [The participation of dehydrogenases in retinol metabolism].
AB  - Retinoids are essential in cell growth and development as well as for maintenance
      of normal function of epithelia and vision. The metabolism of retinol is
      regulated by a few group of enzymes that control conversion of retinol to active
      retinoid aldehydes and retinoic acid. The enzymes involved in the first step of
      retinol metabolism belong to the alcohol dehydrogenase (ADH) and short-chain
      dehydrogenase (reductase) (SDR), which catalyze oxidation of retinol to
      retinaldehyde. The main izoenzymes of ADH that have been proposed to participate
      in this reaction are ADH I and IV. The next step in metabolism of retinol is
      conversion of retinaldehyde to retinoic acid by acting of aldehyde dehydrogenase
      (ALDH).

PMID- 19112850
TI  - [Chemoprevention of esophageal squamous cell carcinoma--clinical trials].
AB  - Esophageal squamous cell carcinoma is one of the most lethal malignances of
      digestive tract. Epidemiological data confirmed influence of the diet especially
      Mediterranean one that decreases the risk of cancer. High consumption of fresh
      vegetables and fruits, mainly citrus and tea drinking, also has a beneficial
      effect on decreasing incidence of the cancer. High intake of various antioxidants
      and natural fibers found in the plant diet as well as prolonged administration of
      cyclooxygenase-inhibitors, especially aspirin, plays also a protective role.
      Results of sparse, prospective, randomized trials on chemoprevention of
      esophageal squamous cell carcinoma are not so unequivocal. Supplementation of six
      traditional Chinese herbs, retinamide and riboflavin provided the most promising
      effects, but intake of multiple vitamins and minerals, including calcium and
      decaffeinated green tea, was ineffective. However, the studies were performed on
      small populations inhabiting select Chinese provinces known for their high
      esophageal cancer incidence. Due to a number of limitations, the collected data
      cannot be compared directly to other populations who are exposed to different
      environmental factors and with different genetic predispositions.

PMID- 19112851
TI  - [Are there any clinical evaluations confirming higher incidence of skin cancers
      as a result of pimecrolimus therapy?].
AB  - Pimecrolimus (SDZ ASM 981), nonsteroid anty-inflammatory ackomycin-derived drug
      has more and more indications in dermatology. It has been recommended in therapy
      of atopic and contact dermatitis at the beginning. Nowadays pimecrolimus is used
      in the treatment of seborrhoic dermatitis, post-steroidal rosacea, bullous
      diseases etc. News reporting higher incidence of skin cancers after pimecrolimus
      application has not been proved clinically. The common use of mentioned
      medication forced us to detailed analysis of references concerning that problem.

PMID- 19112852
TI  - [N-acetyl-beta-hexosaminidase--marker of damage to renal proximal tubules].
AB  - Cells of the renal epithelium synthesize and excrete to urine many enzymes. Among
      more than 50 enzymes produced by epithelial cells of proximal tubules, only few
      have a diagnostic value. Determination of the enzymatic activities in urine is
      sensitive and not invasive method for evaluation the function of renal tubules.
      Urinary N-acetyl-beta-hexosaminidase (HEX) activity is approved and practically
      utilized marker of the renal function. HEX is a lysosomal exoglycosidase taking
      part in catabolism of the sugar chains of glycoconjugates (glycoproteins,
      glycolipids and proteoglycans). HEX catalyses release of N-acetylglucosamine and
      N-acetylgalactosamine from a non reducing ends of glycoconjugates. In urine of
      healthy persons activity of HEX is negligible, but significantly increases after
      damage to the proximal tubules. The cells of renal proximal tubules are very
      sensitive to hypoxia. Therefore all renal processes with hypoxia lead to
      dysfunction of proximal renal tubules and release HEX to urine. Increased
      activity of HEX in urine was found after intoxication by heavy metals,
      nephrotoxic drugs, contrast media, fewer, bacterial as well as immunological
      nephritis and hypertension, diabetes, neoplasms and during renal graft rejection.
      In the paper we presented review of literature concerning HEX, and its presence
      in renal tissue and urine, as well as application in diagnostics.

PMID- 19112853
TI  - [Suicide attempts--possibility of psychoprofilactic].
AB  - Not all suicides can be prevented, however considering the risk of committing the
      suicide on its merits allows physician to undertake treatment of depression and
      at the same way decrease morbidity and mortality rate in population at suicidal
      risk. Every physician should pay special attention to patients with intense
      anxiety and psychomotor agitation or psychotic symptoms like imperative
      hallucinations or persecutory delusions. The important risk factors of committing
      suicide are hopelessness, social isolation, adaptation difficulties after loss,
      divorce, braking up, spouse death. The high suicidal risk group is made up of
      adolescents and advanced in years. In case of any doubts in estimating the
      suicidal risk the psychiatric consultation ought to be taken.

PMID- 19112854
TI  - [Land and marine fauna constituting a threat for recreational divers in the
      tropics].
AB  - Due to intensively growing international tourism, increasing numbers of people
      leave for countries with hot climates, where various threats for human health and
      life exist. Besides climatic and sanitary conditions, a rich fauna, represented
      by predators and venomous animals, can be included. Based on available world
      literature and their own observations, the authors present the threats that a
      tourist can possibly encounter whilst relaxing on the beach or during
      recreational diving in tropical waters. When staying in water, a large threat is
      posed by marine fish of prey (sharks, barracuda, muraena), Cnidaria (jellyfish,
      corals, anemones) and venomous animals (fish, sea snakes). On land, on the other
      hand, a threat can be posed by venomous arthropods (scorpions, spiders) and
      Hymenoptera insects. The study presents the most important representatives of
      fauna present in coastal areas frequently visited by diving enthusiasts. Also,
      clinical image and conduct in the case of body injures are discussed.

PMID- 19112855
TI  - [Value of mfVEP test in pituitary tumors diagnosis].
AB  - PURPOSE: To evaluate the mfVEP test in detection of the optic nerve neuropathy in
      pituitary tumors. MATERIAL AND METHODS: We examined 30 eyes of 15 patients with
      confirmed by MRI pituitary tumors (7 patients with macroadenomas and 8 patients
      with microadenomas). In all patients the routine ophthalmologic examination,
      multifocal visual evoked potentials (mfVEP) and standard static perimetry
      (central 24-2 threshold), were performed. The control group consisted of 30 eyes
      of 15 healthy persons. RESULTS: In 53% (16/30) of eyes manifested changes in
      static perimetry and/or in mfVEP test. In 13% (4/30) of eyes abnormal static
      perimetry and mfVEP were simultaneously observed. The only mfVEP abnormalities
      were the most frequent feature and were observed in 30% (9/30) of eyes. Only
      abnormal static perimetry results were observed in 10% (3/10) of eyes. In those
      eyes in related areas of mfVEP recordings the mean peak-to-peak amplitude was
      significantly reduced compare to the control group. In mfVEP test statistically
      significant peak-to-peak amplitude reduction was observed in superotemporal
      quadrants in comparison to the control group (p < 0.009). CONCLUSIONS: MfVEP can
      be useful test in the optic nerve dysfunction/ neuropathy diagnosis in patients
      with pituitary tumors.

PMID- 19112856
TI  - [Posterior polymorphous dystrophy--changes in corneal morphology in confocal
      microscopy].
AB  - PURPOSE: To describe the in vivo conocal microscopic findings in posterior
      polymorphous dystrophy (PPD). MATERIAL AND METHODS: Eleven patients (22 eyes)
      with PPD suspected or clinically diagnosed were examined using scanning slit
      white light confocal microscopy (ConfoScan 3, Nidek Technologies). RESULTS:
      Endothelial cell densities ranged from 716 to 2380 cells/mm2 and endothelial
      polymegathism was noted in all cases. In 5 cases PPD changes was reported
      unilateral. Confocal microscopy demonstrated a variety of vesicular and linear
      abnormalities. In 13 eyes exhibited bright, nucleus-like structures within
      endothelial cells. Stromal edema was noted in 4 cases. CONCLUSIONS: To our
      knowledge, we present the largest case series of PPD imaged by in vivo confocal
      microscopy. Confocal microscopy images of PPD are very characteristic. This
      method allows to confirm presumptive or to identify final diagnosis. Our study
      enhances the value of confocal microscopy in detection and monitoring corneal
      abnormalities.

PMID- 19112857
TI  - [Central corneal thickness measurement by optical coherence tomography after Nd:
      YAG capsulotomy in patients with posterior capsule opacity].
AB  - PURPOSE: Opacification of the posterior capsule remains the most frequent
      complication of cataract-intraocular lens surgery. Nd: YAG laser capsulotomy is
      actually the most common procedure performed to remove the posterior capsule
      opacification. YAG laser secondary posterior capsulotomy can be associated with
      significant complications. Possible problems include among others, corneal
      oedema. Our study has to determine whether the neodymium:yttrium-aluminium-garnet
      (Nd: YAG) capsulotomy performed in postoperative posterior capsule opacification,
      has an impact on corneal thickness measured by means of the optical coherence
      tomography. MATERIAL AND METHODS: 55 patients (43 females and 12 males), who
      underwent Nd: YAG capsulotomy in posterior capsule opacification, were enrolled
      to the study. Mean age was 65.1 years (range 23-87). Patients were examined
      before and one day, week, month, three months and six months after Nd: YAG
      capsulotomy. Central corneal thickness was measured with use of OCT, anterior
      chamber depth with OCT, endothelial cell density was estimated with specular
      microscopy. Besides, slit lamp examination, including fundus examination, and
      intraocular pressure measurement were performed. Visual function was assessed in
      terms of best corrected distance visual acuity by means of EDTRS type charts.
      Median of the total laser power and single impact laser power and count of
      impacts were determined. In all cases medical history was taken and analyzed.
      RESULTS: Statistically, significant changes of central corneal thickness at one
      day, week, month and three months after capsulotomy were observed. Highest
      relative percentage change at first day (1.9) was noted. Statistically
      significant correlation between central corneal thickness change and total laser
      power and single impact laser power was found in patients 1 month and 3 months
      after treatment. CONCLUSIONS: (1) Only temporary central corneal thickness
      increase was observed as assessed by means of OCT. (2) Nd: YAG capsulotomy should
      be performed with the minimal possible energy delivered to the eye.

PMID- 19112858
TI  - [Ocular changes in course of Mycohacterium tuberculosis infection--own
      observations].
AB  - Ocular tuberculosis occurs rarely and causes many diagnostic difficulties. The
      aim of this paper is to provide an analysis of diagnostic problems of ocular
      changes as a consequence of Mycobacterium tuberculosis infection in children.
      Between 2006 and 2007 there were 7 children at the age 8 to 16 years old, treated
      in Ophthalmic Department. The infection or contact with Mycobacterium
      tuberculosis was diagnosed through the range of examination. Diagnosis of
      tuberculosis included chest radiography, computed tomography of lungs, tuberculin
      skin test and bronchoscopy. Gastric and bronchial aspirates were used for
      bacterial and genetic investigations. In eyes with ocular tuberculosis there were
      various intraocular changes. The most common clinical presentation occurred by
      intermediate uveitis, posterior uveitis and optic neuritis. 5 children were
      treated with antituberculous drugs, 2 children were observed without treatment.
      Examination and treatment of ocular tuberculosis required cooperation with
      specialists of pulmonary diseases.

PMID- 19112859
TI  - [Profile of selected cytokines in various forms of uveitis].
AB  - PURPOSE: The estimation of the level of selected inflammatory mediators in serum
      of patients with various types of uveitis. MATERIAL AND METHODS: The level of IL
      1, IL-6 and TNF was assessed by means of microbiological tests and ELISA test in
      the group of 60 patients with uveitis, divided as regards to the character of
      uveitis and the type of the treatment and in control group. RESULTS: The levels
      of IL-1, IL-6 and TNF were higher in serum of patients with uveitis then in the
      control group. Patients with known etiology of uveitis had higher level of IL-6
      and TNE Patients with autoimmunological etiology of uveitis had higher level of
      IL-1 and IL-6 than volunteers in control group. CONCLUSIONS: Higher levels of
      cytokines in serum of patients with uveitis than in control group indicate the
      activation of immunological response in various types of uveitis.

PMID- 19112860
TI  - [Is Helicohacter pylori infection associated with CRS occurrence?].
AB  - Upper gastrointestinal tract endoscopy was performed in 14 patients with
      clinically determined central serous chorioretinopathy to detect eventual
      Helicobacter pylori infection. In 11 patients Helicobacter pylori infection was
      detected using urease test and histopathological examination. Obtained results
      confirm suggestions that Helicobacter pylori infection may be a factor associated
      with CRS etiopathogenesis. To understand those correlations large studies and
      large patients population are to be performed.

PMID- 19112861
TI  - [The role of chemokines CCL3/ MIP-1 alfa and CCL4/ MIP-1 beta in pathogenesis of
      dry eye syndrome].
AB  - PURPOSE: To evaluate the concentration of chemokines CCL3/ MIP-1 alfa and CCL4/
      MIP-1 beta in film tears in patients with dry eye syndrome. MATERIAL AND METHODS:
      Tears samples were collected from 62 patients with dry eye syndrome and 18
      patients from control group. The concentration of chemokines in film tears were
      determined by immunoenzymatic assay ELISA. RESULTS: We found statistically
      increased levels of chemokines CCL3/ MIP-1 alfa and CCL4/ MIP-1 beta in film
      tears of patients with dry eye syndrom compared with control group. CONCLUSION:
      Inflammation may play role in pathogenesis of dry eye syndrome.

PMID- 19112862
TI  - [Safety and efficacy of using bevacizumab in the treatment of exudative age
      related macular degeneration].
AB  - PURPOSE: To evaluate the efficacy and safety of intravitreal bevacizumab
      administered on "as required" basis in patients with exudative age-related
      macular degeneration (AMD). MATERIAL AND METHODS: A prospective uncontrolled
      cohort study of patients with exudative AMD treated with intravitreal bevacizumab
      administered "as required" based on PRONTO reinjection criteria. Main outcome
      measures include standardized best-corrected visual acuity (BCVA) and central
      macular thickness (CMT) measured with optical coherence tomography (Stratus OCT).
      RESULTS: 153 eyes of 153 consecutive patients with AMD were treated with
      intravitreal bevacizumab injection, followed monthly and reinjected "as
      required". Mean follow-up time was 14.2 weeks (4-52 weeks). Distance BCVA
      improved from 0.79 log MAR at baseline to 0.69 at 4 weeks, 0.7 at 8 weeks, 0.64
      at 12 weeks, 0.71 at 16 weeks and 0.63 at 20 weeks (p<.05). Near BCVA improved
      from 0.13 at baseline to 0.22 at 4 and 8 weeks, 0.25 at 12 weeks, 0.22 at 16
      weeks and 0.28 at 20 weeks (p<.05). Mean CMT decreased from 395 microm at
      baseline to 265 at 4 weeks, 260 at 8 weeks, 268 at 12 weeks, 255 at 16 weeks and
      257 at 20 weeks (p<.05). Mean time between first and second injection was 91.9
      days, and between second and third injection 99.7 days. No adverse events were
      observed. CONCLUSIONS: Short-term results suggest that intravitreal bevaciuzmab
      administered "as required" is safe and effective in patients with exudative AMD.
      "As required" schedule may decrease the risk of adverse events and lower the cost
      of treatment.

PMID- 19112863
TI  - [Efficacy of pneumatic traheculoplasty (PNT) in patients with open angle glaucoma
      and ocular hypertension--a preliminary report].
AB  - PURPOSE: To evaluate the efficacy of PNT in lowering intraocular pressure (IOP)
      in patients treated for open angle glaucoma (OAG) and ocular hypertension (OH).
      MATERIAL AND METHODS: The study group consisted of 24 eyes of 14 patients (10 F
      and 4 M), aged from 35 to 72 (mean 53.7 +/- 8.7) who were treated for OAG or OH.
      Twelve patients were treated with prostaglandin analogues (PA) in monotherapy,
      one patient with PG and nonselective beta-bloker (BB) and one patient with PG, BB
      and topical carbonic anhydrase inhibitor (CAI). The baseline mean IOP measured
      with Goldmann tonometry one hour before first PNT procedure was 20.7 +/- 3.3 mmHg
      (range 16-27). The PNT was performed routinely at 0 and 7-10 day using PNT Unit
      1000-Coronado (Ophthalmic International, Inc., Fountain Hills, Arizona, U.S.A.).
      Then the IOP was measured monthly and if increased to the preoperative values the
      procedure was repeated. The mean observation time was 6 months, with the shortest
      and longest follow-up being 4 and 12 months, respectively. The IOP changes were
      estimated one hour after the first PNT on day 0, then on day 7-10, after 1, 2, 3,
      4, 5 and 6 months. A paired Student's t test was used for statistical analysis.
      RESULTS: The mean IOP measured one hour after PNT was 19.26 +/- 4.0 mmHg (p =
      0.17). After 7 days mean IOP was 17.35 +/- 2.64 mmHg (p<0.01), after one month
      16.52 +/- 2.81 mmHg (p<0.01) and after next months 16.37 +/- 2.61 mmHg (p<0.01),
      17.63 +/- 2.28 mmHg (p<0.01), 15.64 +/- 2.06 mmHg (p<0.01), 16.14 +/- 3.42 mmHg
      (p< 0.01) i 16.64 +/- 3.14 mmHg (p<0.01), respectively. The mean IOP reduction
      was 1.48 mmHg (7.14%) one hour after PNT procedure, 3.39 mmHg (16.35%) after 7-10
      days, 4,22 mmHg (20.35%) after one month, then respectively 4.37 mmHg (21.07%),
      3.11 mmHg (15.02%), 5.10 mmHg (24.59%), 4.60 mmHg (22.18%) and 4.10 mmHg (19.77%)
      after 2, 3, 4, 5 and 6 months of observation. In 8 eyes the procedure was
      repeated again after 3 months, in 4 eyes after 6 months and in 2 eyes after 12
      months. After the procedures transient moderate conjunctival hyperemia was
      observed in 24 eyes (100%) and mild subconjunctival hemorrhagies in 4 eyes (16%).
      Lasting a few hours after the PNT procedure foreign body sensations occured in
      3/14 patients (21%). CONCLUSIONS: PNT is an effective method of lowering IOP in
      patients treated for OAG and OH.

PMID- 19112864
TI  - Transitory hypotonia as a prognostic factor in combined procedures of
      phacoemulsification and deep sclerectomy.
AB  - PURPOSE: To determinate the influence of hypotonia on the effectiveness of
      phacoemulsification and deep sclerectomy performed simultanously with the SK-gel
      implant in 15 months follow up. MATERIAL AND METHODS: The retrospective analysis
      comprised group I (IOP < or =6 mm Hg)--50 eyes and group II (IOP > 6 mm Hg)--75
      eyes. Uncontrolled primary open-angle glaucoma and coexisting cataract were the
      indication. DBCVA, IOP anterior segment and eye fundus were assessed as well as
      the number of antiglaucoma medications. The patients were examined on the first
      and the seventh day as well as at 1, 3, 6, 12 and 15 months. IOP < or = 12.15 and
      18 mm Hg was accepted as surgical success criterion. T - Student test was used in
      statistical analysis and variance was analysed. The survival analysis was worked
      out with Kaplan-Meier method. RESULTS: After 15 months the decrease of mean IOP
      was obtained in group I by 35.9% (p < 0.05) and in group II by 33.5% (p < 0.05).
      There were no statistical differences between the number of the applied
      antiglaucoma medications in the investigated groups. Finally, a qualified
      surgical success was obtained for the criterion < or = 18 mmHg in 97.7% of cases
      in group I and in 87.9% in group II (p= 0.013). For the criterion < or =15 mm Hg-
      in group I 84.3% and in group II 66.4% (p < 0.001), whereas for the criterion <
      or = 12 mm Hg respectively in group 141.2% and in group II 39.3% (p = 0.015).
      DCBVA 15 months after the surgery was 0.84 +/- 0.24 in group I and 0.71 +/- 0.25
      in group II. At the end of the follow up no significant differences of DBCVA were
      found between the investigated groups (p > 0.05). CONCLUSIONS: Hypotonia is an
      important positive prognostic factor in the first 24 h after surgery in the case
      of phacoemulsification, performed at the same time with deep sclerectomy.

PMID- 19112865
TI  - Pupillary block glaucoma in child with persistent hyperplastic primary vitreus-
      case report.
AB  - PURPOSE: The purpose of this paper is to present the case of a patient with PHPV,
      in whom the complication in a form of pupillary block glaucoma was observed as a
      result of idiopathic and complete lens dislocation into the anterior chamber.
      MATERIAL AND METHODS: Examination was performed on 3 months old boy with grey
      pupilla reflex, noted from the birth, in the right eye. Microphthalmia,
      subcapsular cataract and anterior-posterior form of PHPV was found in that eye.
      The patient was qualified to surgical treatment. Before the appointed time of
      operation the increased intraocular pressure and significant globe enlargement
      were noted. The reason of that was pupillary block caused by lens dislocation
      into the anterior chamber. One-step surgical procedure: trabeculectomy,
      lensectomy and cutting out the retrolenticular fibrous membrane, was performed in
      urgent course. RESULTS: Performed complicated and difficult surgical treatment
      resulted in normalizing IOP and created good conditions for vision rehabilitation
      for the child. Postoperatively the detachment of the choroid was noted as a
      transient complication. CONCLUSIONS: In this case luxated lens and pupillary
      block was caused by constriction of retrolenticular fibrous membrane. Early
      surgical intervention is necessary to prevent progressive pathologic changes in
      eyes with this developmental disorder and to obtain the best possible visual
      results.

PMID- 19112866
TI  - Recurrent benign pleomorphic adenoma of the lacrimal gland--a case report.
AB  - Benign pleomorphic adenoma (mixed tumor) is the most frequently occurring tumor
      of epithelial origin. It occurs in serous glands, most frequently in parotid
      glands and rarely in small palatine glands, cheek glands, palatine tonsils and
      the lacrimal gland. This study is a description of the therapeutic management of
      a patient with recurrent pleomorphic adenoma of the lacrimal gland. In 1996, a 35
      year old male patient underwent surgery to remove a tumor of the left orbit.
      Histopathological examination revealed pleomorphic adenoma. From 1998, the
      patient had observed increasing exophthalmus of the left eyeball. In 1999, vision
      distortion and headaches had begun. In 2005, from a cut along the upper-outer
      edge of the left orbit, an elastic and soft tumor 1 cm in diameter was removed
      from soft tissues of the upper eyelid. Then, with the use of the side orbitotomy
      technique, the orbit was opened through incision of the temporal muscle and
      removal of the orbital side wall. An eyelid nodule of 0.8 mm in diameter was
      removed together with an elastic and hard tumor of size 2.5 x 1 cm. The result of
      the histopathological examination of the palpebral tumor was pseudocystic tumor
      and of the orbital tumor was pleomorphic adenoma. CONCLUSION: patients resected
      for pleomorphic adenoma of the lacrimal gland require a long period of
      postoperative observation and periodic ophthalmologic examination.

PMID- 19112867
TI  - [Optical coherence tomography (OCT) in central retinal occlusion with sparing
      cilioretinal artery--a case report].
AB  - The authors present a case of central retinal artery occlusion with sparing
      cilioretinal artery in 62 year old woman with sudden decrease of visual field in
      the right eye. The diagnosis of central retinal artery occlusion
      (ophthalmological examination, fluorescein angiography, field of vision and
      optical coherent tomography) was performed at the begining and after 1 month. In
      acute phase, optical coherence tomography reveals increased thickness and
      reflectivity of the inner retinal layer and decreased reflectivity of the outer
      retinal layer. After one, three and six months OCT demonstrates a decrease of
      reflectivity and thickness of the inner retina and increase of reflectivity of
      the outer layer. Spectral OCT performed after six months from the beginnig of the
      disease shows atrophy of the retinal neurosensory layer.

PMID- 19112868
TI  - [Small choroidal melanoma--a diagnostic problem].
AB  - The aim of this paper is to present the most common diagnostic problem associated
      with a small choroidal melanoma. In some cases other lesions such as a choroidal
      naevus, an exudative type of age related macular degeneration (AMD) with the
      presence of subretinal haemmorrhage, retinal pigment hypertrophy, choroidal
      haemangioma and choroidal metastatic tumours may mimic small choroidal melanomas.
      Based on the literature and on our own experience we present the basic clinical
      features of these lesions, their characteristic fluorescein angiography,
      indocyanine green angiography and ultrasonography pictures that can be helpful in
      differential diagnosis.

PMID- 19112869
TI  - [Possibilities of applying cannabinoids' in the treatment of glaucoma].
AB  - Over a period of several decades numerous scientific research has proven that,
      regardless of the route of administration, cannabinoids are able to decrease
      intraocular pressure. What is more, these compounds are characterized by
      neuroprotection and vasodilatation properties, that additionally substantiate
      it's therapeutic utility in conservative treatment of glaucoma. So far, it has
      not been described in details what mechanism is used to lower the intraocular
      pressure by cannabinoids. Nevertheless, the presence of endocannabinoid receptors
      in structures of the eye responsible for formation and outflow of aqueous humor
      is an explanation for effectiveness of these compounds, when administered in
      topical form. These days, with the aid of modern pharmacological technology are
      available significantly bigger possibilities of improving bioavailability of
      cannabinoids administered to the eye than in the past, as well as limitation of
      it's undesired side effects.

PMID- 19112870
TI  - [Role of the retinal pigment epithelium (RPE) in the pathogenesis and treatment
      of diabetic macular edema (DME)].
AB  - Pigment epithelium-derived factor (PEDF) has recently been shown to be the most
      potent inhibitor of angiogenesis in the mammalian eye, suggesting that loss of
      PEDF is involved in the pathogenesis of proliferative diabetic retinopathy.
      However, a protective role for PEDF in pericyte loss requires elucidation.
      Present studies suggest that PEDF proteins could protect against advanced
      glycation end product (AGE), which induce injury in retinal pericytes.
      Substitution of PEDF proteins may be a promising strategy in the treatment of
      patients with early diabetic retinopathy. Therefore, injury of RPE is the basic
      condition, not only of the progress of neovascularization, but initiation of
      early diabetic microangiopathy and macular edema as well. Recently new
      intravitreal drugs being used in the treatment of eye diseases with increased
      level of VEGE. Intravitreally administered a human, monoclonal anti-VEGF agent
      acts only as symptomatic treatment. It does not eliminate hypoxia and requires
      repeated administration. It is worth emphasizing, that VEGF functions are not
      limited to active angiogenesis, but also seems to require the maintenance and
      differentiation of mature blood vessels, such as the choriocapillaris. Therefore,
      delivery of these anti-VEGF treatments needs to be specific to sites of
      neovascularization or limited to a short duration, to prevent disruption of the
      normal vasculature. The effective method, which preserves RPE, improves
      oxygenation and release traction on the macula, leading to decreased permeability
      with subsequent resolution in DME, is pars plana vitrectomy with ILM peeling.
      There are several investigations that support the theoretical value of vitrectomy
      for the treatment of DME. Intraoperative administration of anti-VEGF agent and
      corticosteroids may additionally improve results of operative treatment.

PMID- 19112871
TI  - [Mutations in mitochondrial DNA in ocular diseases--Leher's hereditary optic
      neuropathy and Kearns' syndrome].
AB  - Mitochondrial diseases are caused by mitochondrial structure aberrations and
      function deficiency. The clinical heterogeneity of mitochondrial diseases is
      associated with the type of causing mutations (de novo or maternally transmitted
      mutations), and several aspects of mitochondrial genetics and inheritance,
      including heteroplasmy. In this paper, we explain the basics of mitochondrial
      genetics and inheritance as well as genetic background of mitochondrial related
      disorders: Leber's hereditary optic neuropathy and Kearns' syndrome.

PMID- 19112872
TI  - Who enrolls in college death education courses? A longitudinal study.
AB  - A major concern for the pioneers in death education at the college level was the
      need to recognize those students who enrolled in the course in order to get help
      with death related issues, primarily suicidal thoughts and unresolved grief.
      Despite anecdotal evidence of these at-risk students, this concern has yet to be
      addressed adequately. This may be due in part to the paucity of empirical
      evidence. The authors bring over 30 combined years of experience in teaching
      death education at the university level. They have their own anecdotal stories.
      They also have empirical evidence. This article addresses the question of why
      students take death education courses in college by examining data collected from
      death education classes over a span of 20 years and 3 decades (1985-2004). The
      results document the magnitude and consistency of the at-risk student. The
      authors discuss the precautionary steps they take and call for a renewed
      discourse on ethical considerations in death education.

PMID- 19112873
TI  - Exploring the beliefs underlying attitudes to active voluntary euthanasia in a
      sample of Australian medical practitioners and nurses: a qualitative analysis.
AB  - A qualitative study explored beliefs about active voluntary euthanasia (AVE) in a
      sample (N = 18) of medical practitioners and nurses from Australia, where AVE is
      not currently legal. Four behaviors relating to AVE emerged during the
      interviews: requesting euthanasia for oneself, legalizing AVE, administering AVE
      to patients if it were legalized, and discussing AVE with patients if they
      request it. Using thematic analysis, interviews were analyzed for beliefs related
      to advantages and disadvantages of performing these AVE behaviors. Medical
      practitioners and nurses identified a number of similar benefits for performing
      the AVE-related behaviors, both for themselves personally and as health
      professionals. Benefits also included a consideration of the positive impact for
      patients, their families, and the health care system. Disadvantages across
      behaviors focused on the potential conflict between those parties involved in the
      decision making process, as well as conflict between one's own personal and
      professional values.

PMID- 19112874
TI  - How religion comforts the dying: a qualitative inquiry.
AB  - Although considerable social science research has explored religiosity and death
      anxiety, and many have theorized that religion comforts the dying, with
      speculations on the mechanisms by which religion comforts, very little research
      has asked people who were actually dying to discuss religion. This article
      reports on answers given by 38 hospice patients to the questions: Is religion a
      comfort to you? How does religion comfort you? This study found that religion,
      when it comforted these dying people, did so by offering a relationship to the
      dying, by giving the hope of life after death, through identifications, and
      through the assurance of cosmic order. The authors suggest theoretical
      perspectives accounting for these functions.

PMID- 19112875
TI  - Death anxiety in institutionalized and non-institutionalized elderly people in
      Spain.
AB  - To know the level of death anxiety using the Templer Death Anxiety Scale (DAS)
      (1970) (Ramos's Spanish adaptation, 1982)) we chose subjects older than 65 years
      (N = 227) to study, on one hand, the existing relation between cognitive
      affective reactions toward death and the perception of the passing of time and,
      on the other, a group of variables which include the place of residence, age,
      gender, life reflection, health disorders, psychological problems, religious
      aspects, and socio-demographics features. To undertake this, a questionnaire was
      administered in which the participants answered according to their degree of
      agreement to several alternatives. The data indicates, by means of an analysis of
      variance, significant differences between these variables and death anxiety, with
      the exception of the religious aspects and civil state.

PMID- 19112876
TI  - Islam and suicide: a short personal communication.
AB  - Islamic countries display lower suicide rates compared to the other countries of
      the world. Since most studies dealing with the relationships between Islam and
      suicide have focused on the extent of the problem and not the underlying
      mechanisms, the focus of this brief communication is to provide a rather more in
      depth discussion regarding the mechanism of this relation. It also covers issues
      which may have an adverse effect on suicide within Islamic countries and
      consequently tries to sketch a path ahead in the area of suicide research within
      the Islamic countries.

PMID- 19112877
TI  - Stem cells: a primer.
AB  - Having great therapeutic and biotechnological potential, stem cells are extending
      the frontier in medicine. Not only replace dysfunctional or damaged cells, the so
      called regenerative medicine, stem cells may also offer us new perspectives
      regarding the nature of aging and cancer. This review will cover some basics of
      stem cells, their current development, and possible applications in medicine.
      Meanwhile, important remaining challenges of stem cell research are discussed as
      well.

PMID- 19112878
TI  - Human somatic cell nuclear transfer.
AB  - Human Somatic Cell Nuclear Transfer (hSCNT) is a required procedure before
      derivation of autologous embryonic stem cells (ESC) for clinical treatment. The
      debate between ethical concerns and the potential for clinical application is
      still ongoing. Currently, the milestone of deriving hSCNT blastocysts has been
      achieved. The developmental mechanism for SCNT is similar to the developmental
      mechanism for fertilized embryos without sperm fertilization. The hSCNT procedure
      consists of enucleating an oocyte and replacing with a donor somatic cell
      nucleus; this procedure is more difficult than a parthenogenetic procedure. The
      difficulties of SCNT involve the cell cycle synchronization between the donor
      nucleus and arrested ooplasm, suboptimal activation of reconstructed "zygotes",
      suboptimal culture condition, and incomplete genetic remodeling/epigenetic
      modification. There are protocols intended to overcome the difficulties, but no
      center has derived hSCNT ESC yet.

PMID- 19112879
TI  - Human pluripotent stem cells: current status and future perspectives.
AB  - Since human embryonic stem cells (hESCs) were first derived from preimplantation
      blastocysts, the advent of hESC-based therapy for a wide range of cellular
      degenerative diseases has been greatly anticipated. However, standard methods for
      hESC derivation result in embryo destruction and have been under intense ethical
      debate. Various alternative approaches have been devised since then generate
      pluripotent stem cells (PSCs) without embryo destruction. These new advances in
      stem cell derivation include the derivation of human-induced PSCs by introducing
      genetically-defined factors into adult somatic cells, the generation of hESCs
      from single blastomeres, and the generation of non-human primate ESCs through
      somatic cell nuclear transfer (SCNT). They have overcome the major problems
      inherent in conventional hESCs. With these advances in the derivation of new PSC
      types, it is essential to carefully examine the nature of the pluripotency
      expressed by these cells and the mechanism regulating the reprogramming process
      through large scale genetic and epigenetic screening. We reviewed these new
      methods of hPSC derivation and addressed some of the problems associated with
      these advances. A brief summary of new advances in genome-wide chromatin
      immunoprecipitation-sequencing (ChIP-seq) technology and their implications for
      stem cell research were provided and discussed.

PMID- 19112880
TI  - Human ES cell derived cardiomyocytes for cell replacement therapy: a current
      update.
AB  - Cardiovascular diseases are the leading cause of death globally. The pluripotency
      and indefinite proliferative capacity of embryonic stem (ES) cells make them a
      promising candidate for the cell replacement therapy where the damaged cells are
      replaced by the functional cells derived from stem cells in vitro. Emerging
      results with human ES cells for the myocardial repair are encouraging, but this
      approach is still in its infancy and is under extensive investigation. The daily
      upcoming experimental observations are reinforcing the solid hope that ES cells
      will be the potential source for use in cell replacement therapy. Although this
      demands serious considerations ethically and on practical applicability, the
      newly upcoming discoveries show that the adult human fibroblasts can be
      reprogrammed to embryonic stem cell like cells (called induced pluripotent stem
      cells) which can be used for cell replacement therapies. Remarkably, this
      obviates the need for the embryo destruction and overcomes related immunological
      problems which are the long time hurdles for the ES cell based cell replacement
      therapy. This review weighs the actual stand off in the human ES cells based cell
      replacement therapy for the treatment of cardiovascular degenerative diseases
      with a special emphasis on the hurdles and challenges to be resolved before the
      onset of clinical trials and the potential of the recently reported "induced
      pluripotent stem cells" for their use in cell replacement therapy.

PMID- 19112881
TI  - Identification of genetic networks during mesenchymal stem cell transformation
      into neurons.
AB  - The aim of this experiment is to identify related genes for human umbilical
      mesenchymal stem cells transformation into nervous cells. After the human
      umbilical mesenchymal stem cells were treated with neuronal conditioned medium
      (NCM) for 9 days, the gene expression groups are compared to those only treated
      with DMEM. The related genes for cell cycles, the human umbilical mesenchymal
      stem cells treated with DMEM increases the amount of cells that remain in the
      G2/M phase and S phase, including CAV1, EBF, NRG1, CDH13, MLH1. After treatment,
      the human umbilical cord mesenchymal stem cells with NCM for 9 days, gene
      expression related to the G0/G1 phase are also increased, including MYC, CSF3,
      PETN. Gene expressions related to neural regeneration and neural stem cells also
      increase significantly, such as CXCL1, BMP2, NRCAM, FGF2, SPG7. This study
      thereby provides a foundation for a more detailed understanding of HUMSCs
      neuronal differentiation.

PMID- 19112882
TI  - Survival and differentiation of neuroepithelial stem cells following
      transplantation into the lateral ventricle of rats.
AB  - Neuroepithelial stem cells (NEPs) demonstrate a high potential for self-renewal
      and differentiation during embryonic development. To explore the survival and
      differentiation of NEPs in vivo, we isolated NEPs from green fluorescence protein
      (GFP) transgenic embryos and transplanted into the lateral ventricle of rats. In
      vitro culture, NEPs proliferated into neurospheres and differentiated into both
      neurons and glia. When transplanted into the lateral ventricle of rats, these GFP
      positive NEPs (GFP+ NEPs) survived and attached to the wall of ventricle.
      Moreover, grafted cells differentiated into neuron-specific enolase (NSE)
      positive neurons and glial fibrillary acidic protein (GFAP) positive astrocytes
      and migrated into the host brain. Thus, our results indicate that NEPs can
      survive and differentiate into neurons and astrocytes in the lateral ventricle
      following transplantation.

PMID- 19112883
TI  - Chondrogenic differentiation of human mesenchymal stem cells from umbilical cord
      blood in chemically synthesized thermoreversible polymer.
AB  - Scaffolds provide a template for cell distribution, growth, differentiation and
      extracellular matrix accumulation in a three-dimensional environment. Recent
      studies have demonstrated the potential of scaffolds for enhancing articular
      cartilage repair both in vitro and in vivo investigations. Mesenchymal stem cells
      derived from human umbilical cord blood (CBMSCs) have been characterized by their
      multipotency to differentiate into mesenchyme-lineage cell types, including
      chondrocytes, osteoblasts, and adipocytes. In this study, chondrogenesis of
      CBMSCs was performed in a chemically synthesized thermoreversible gelation
      polymer (TGP). CBMSCs were embedded in the TGP and supplemented with ascorbic
      acid and transforming growth factor-beta 3. After a 4-week induction, the results
      showed that CBMSCs formed into spheroid pellets and increased in size. The
      induced cells in the TGP expressed specific mRNA of collagen type II, aggrecan,
      and Sox9 for chondrocytes. Furthermore, CBMSCs embedded in TGP had higher ratio
      of glycosaminoglycan secretion to DNA content than the traditional induction
      method by aggregating pellet culture. These results demonstrated that chemically
      synthesized TGP provided a competent 3-dimentional culture environment for CBMSCs
      to differentiate into chondrocytes and may be applied clinically to induce
      chondrogenic differentiation of CBMSCs for cartilage repair in the future.

PMID- 19112884
TI  - Impact factor of the Chinese Journal of Physiology in 2007: building a strong
      foundation.

PMID- 19112885
TI  - [Determination and fingerprint analysis of tetramethylpyrazine and ferulic acid
      in Ligusticum chuanxiong].
AB  - OBJECTIVE: To determine the contents of tetramethylpyrazine (TMP) and ferulic
      acid in Ligusticum chuanxiong from different producing areas and seasons.
      METHODS: The contents of TMP and ferulic acid were determined by HPLC, and then
      analyzed by Chromatographic Fingerprints. RESULTS: The contents of TMP and
      ferulic acid from different seasons were obviously different from each other. It
      was much higher in "laoxiong" than that in "naixiong". The similarity of
      fingerprints was high if the samples were collected from the same season, or the
      same areas, but not different seasons. CONCLUSIONS: The contents of TMP and
      ferulic acid were different from different producing areas. The evident variety
      of Ligusticum chuanxiong's fingerprints from different collecting seasons,
      Laoxiong and Naixiong, was not relevant for clinical use as the same medicine.

PMID- 19112886
TI  - [A study on technology of harvest and process for stem and fruit of Akebia
      trifoliate].
AB  - The harvest and process experiment were carried out on the stem and fruit of
      Akebia trifoliate. The results showed that the medicinal materials were more
      excellent as the collecting period postponed, the quality of main stem from three
      year old was better than those of youngers or first and second branch, such as
      the index of aridity,the color,the mineral content,the maceration extract content
      and airflow trait. Stems collected in the Mid-November were observably better
      than those in the March, May, July and Mid-September. Fruits collected on the
      first day of September were more excellent than those in July, August and
      October. The processing technology of the stem and fruit was consisted of harvest
      and drying. The quality and character presented no difference after arid or
      drying at 60 degrees C temperature.

PMID- 19112887
TI  - [Pharmacognostic identification of radix actinidiae chinensis].
AB  - OBJECTIVE: To provide the scientific basis for gruffs identification and
      utilization of Radix Actinidiae chinensis. METHODS: Radix Actinidiae chinensis
      was studied through the morphological, microscopical and UV spectrum
      identifications. RESULTS: There were 1-3 stone cell girdle bands in cork layer of
      root cross section. Sclerotic nests and mucilage cavities which contained calcium
      oxalate raphides existed in phloem. Endodermis cells separated by radial paries,
      were fusiform. In powder, port-hole was deep, striation was manifest, and starch
      grain calcium oxalate acicular crystal was plenty. CONCLUSION: These
      characteristics can provide the scientific basis for gruffs identification of
      Radix Actinidiae chinensis.

PMID- 19112888
TI  - Fingerprint analysis of anti-tumor active polypeptides from Arca subcrenata by
      HPLC.
AB  - RP-HPLC was applied to analyze active polypeptides in Arca subcrenata, and the
      optimal condition for separation was also set up: temperature: 30 degrees C;
      wavelength: 280 nm; flow rate: 1.0 ml/min; Solvent A consisted of 80%
      acetonitrile and 0.1% trifluoroacetic acid (TFA) and solvent B contained 0.1%
      TFA. In this condition, ten samples' fingerprints were gained, in one of which
      the genuine fraction exhibited fourteen "common peaks" representing the
      characteristics of the constituents.

PMID- 19112889
TI  - [Study on fingerprint spectrum of Lonicera macranthoides by HPLC].
AB  - OBJECT: To establish the fingerprint spectrum of Lonicera macranthoides by HPLC.
      METHODS: The column of Hypersil gold C18 (4. 6 mm x 250 mm, 5 microm) was used.
      The mobile phase consisted of Acetonitril-0.05% phosphoric acid with gradient
      elution. The column temperature was 30 degrees C, the detective wavelength was
      240 nm, and the flow rate was 0.5 ml/min. RESULTS: Fingerprint spectrum of
      Lonicera macranthoides was established, and 11 samples of different origin
      Lonicera macranthoides were detected. Ten peaks in the chromatogram were common
      by Similarity Evaluation System for Chromatographic Fingerprints of Traditional
      Chinese Medicine (Version 2004 A). There was a high similarity and each
      chromatographic peak was obtained with good separation and correlation according
      to the technical requirements of fingerprint of Chinese traditional medicine.
      CONCLUSION: This method is accurate, reliable and provides a scientific basis for
      controlling the quality of Lonicera macranthoides.

PMID- 19112890
TI  - [Study on HPLC fingerprint characteristic analysis of Cordyceps sinensis and its
      similar products].
AB  - OBJECTIVE: To study on HPLC fingerprint characteristic analysis of Cordyceps
      sinensis and its similar products. METHODS: To determinate 13 samples of
      Cordyceps sinensis and its similar products by HPLC, and analyze the HPLC results
      with similar appraisal method and graphical methods of multivariate sample in two
      dimensional plane such as the methods of profile, radar chart and constellation
      graph. RESULTS: The similar appraisal method might synthesize the similar degree
      in quantification, while the graphical methods such as profile graph, radar chart
      and constellation graph could show more details about the classification and the
      characteristic of varieties directly. CONCLUSIONS: We recommend the combined
      application of similar appraisal method and the graphical methods due to its
      advantages on the judgment and characteristic analysis of fingerprint.

PMID- 19112891
TI  - [Study on RP-HPLC fingerprints of Panax quinquefolium from Liuba County in Shanxi
      Province].
AB  - OBJECTIVE: To establish a fingerprint analysis method for quality control of
      Panax quinquefolium from Liuba County in Shanxi Province by RP-HPLC. METHODS: A
      gradient mobile system was applied in the experiment. The fingerprints of
      different samples were compared by similarity evaluation software. RESULTS: The
      similarities among different samlpes were high. 14 peaks were identified as the
      characteristic fingerprints of Panax quinquefolium. All samples contained the
      same characteristic peaks, but the content difference of each peak among the
      samples resulted in the difference of their chromatograms. CONCLUSIONS: This
      method is precise with good repeatability and good baseline separation of all the
      chromatographic peaks, so it can be effectively used to assess the quality of
      Panax quinquefolium.

PMID- 19112892
TI  - [Research on chemical constituents from stem of Gymnema sylvestre].
AB  - OBJECTIVE: To study on the chemical constituents from the stem of Gymnema
      sylvestre. METHODS: The constituents were extracted by percolation with ethanol.
      Then the extract was separated by systemic solvent separation methods. The part
      of n-butanol extract was isolated and purified by macroporous adsorptive resins,
      silica gel column chromatography, sephadex gel column chromatography and
      recrystallization. The isolated compounds were identified by spectrum methods.
      RESULTS: Eight compounds were isolated and identified as fallows: Conduritol
      A(I), 1-Heptadecanol(II), Stigmasterol glucoside(III), 1-Quercitol(IV), 1
      Octadecanol(V), Potassium nitrate(VI), Lupeol cinnamate(VII), Stigmasterol(VIII).
      CONCLUSION: Chemical compounds II, III, V, VII are firstly obtained from this
      plant.

PMID- 19112893
TI  - [Studies on chemical constituents of Peucedanum delavayi].
AB  - OBJECTIVE: To study the chemical constituents of the radix and rhizome of
      Peucedanum delavayi. METHODS: The chemical constituents had been separated by
      manifold chromato-graphy methods, and their structures were determined by
      spectral analysis. RESULTS: Fifteen compounds were isolated and identified as
      Umbelliferone(I), Coumurayin(II), Mexoticin(III), Marmesin (IV), Ammijin(V),
      Delton (VI), Selinidin(VII), Anomalin(VII), Isopteryxin(IX), Ferulic acid(X),
      Falcarindiol(XI), Stearic acid(XII), beta-sitosterol(X III), Daucosterol(XIV) and
      d-Mannitol(XV). CONCLUSION: All these compounds are isolated from Peucedanum
      delavayi for the first time.

PMID- 19112894
TI  - [Chemical constituents of antibacterial activity fraction of Angelica
      polymorpha].
AB  - OBJECTIVE: To study chemical constituents of antibacterial activity fraction of
      Angelica polymorpha. METHODS: Compounds were isolated by repeatedly silica gel
      column chromatography and recrystallization. Their structures were identified by
      physical and chemical evidences and spectral methods. RESULTS: Seven compounds
      were obtained from the antibacterial activity fraction, their structures were
      elucidated as: bisabolangelone(I), isoimperatorin (II), oxypeucedanine(III),
      isooxypeucedanine(IV), oxypeucedanin hydrate(V), bergapten(VI), pabulenol(VII).
      CONCLUSION: Bisabolangelone(I) is obtained from this plant for the first time.
      Compound (II)-(VII) belong to linear furanocourmarins.

PMID- 19112895
TI  - [Studies on chemical constituents from rattan of Polygonum multiflorum].
AB  - OBJECTIVE: To study on the chemical constituents from rattan of Polygonum
      multiflorum. METHODS: The chemical constituents were extracted with alcohol and
      were separated with manifold chromatography technique. Their structures were
      determined by spectral analysis. RESULTS: Thirteen compounds were isolated and
      identified as Chrysophanol(I), Physcion(II), Emodin(III), Aloeemodin(IV),
      Rhein(V), Physcion-8-O-beta-D-glucoside(VI), Emodin-8-O-beta-D-glucoside
      (VII),2,3,5,4'-Tetrahydroxy-stibene-2-O-beta-D-glucoside(VIII), Noreugenin(IX),
      Apigenin(X), Daucosterol(XI), beta-Sitosterol(XII), Stearic acid(XIII).
      CONCLUSION: Among these, compounds I, IV-VI, VIII-XI, XIII are isolated from
      rattan of Polygonum multiflorum for the first time.

PMID- 19112896
TI  - [Studies on chemical constituents from Pteris multifida].
AB  - OBJECTIVE: To investigate the chemical constituents of Pteris multifida. METHODS:
      All compounds were isolated and purified by normal column chromatography, paper
      thin layer chromatography and sephadex chromatography. The chemical structures
      were mainly elucidated by ESI mass and NMR spectra. RESULTS: Seven compounds were
      isolated from the methanol extracts of Pteris multifida. In addition to a
      glycoside of sesquiterpene pterosin C-3-O-beta-D-glucoside(1), six flavonoids
      were isolated from S. barbata as fouows: apigenin(2), luteolin(3), apigenin-7-O
      beta-D-glucoside(4), apigenin-7-O-beta-D-glucosyl-4'-O-alpha-L-rhanrnoside(5),
      apigenin-4'-O-alpha-L-rhanrnoside(6) and luteolin-7-O-beta-D-glucoside(7).
      CONCLUSION: Compound(2), (3) and (5), (6) are isolated from Pteris multifida for
      the first time.

PMID- 19112897
TI  - [Effect of total saponins from Panax notoginseng on expession of melatonin
      receptor mRNA in gastric mucosa of stress rats].
AB  - OBJECTIVE: To observe the effect of total saponins from Panax notoginseng (PNS)
      on melatonin receptor (MR) expression and its content in gastric mucosa of stress
      rats. METHODS: Water-immersion restraint stress (WRS) was used to induce stress
      rat models. RevertAid First Strand cDNA Synthesis Kit was used for the reverse
      transcription of the total RNA from gastric mucosa of stress rats. The PCR
      product was analyzed by agarose gel electrophoresis firstly and then by KODAK 1 D
      Image system. The expression level of melatonin 1 (MT1) receptor mRNA was
      calculated with the optimal density of ratio of MT, receptor and GAPDH. RESULTS:
      Six hours after WRS, there were 360 bp positive bands in RT-PCR product of MT1.
      The relative content of MR was lower in the model group than that in the normal
      group. MR content in PNS group and ranitidine group were both higher than that in
      the normal group and the model group (P < 0.05 or P < 0.01). CONCLUSION: There is
      mRNA expression of MT1 receptor in gastric mucosa of stress rats indeed. PNS has
      protective effect on gastric mucosa of stress rats by up-regulating MR
      expression, and its protective mechanism may be related to promoting melatonin
      secretion or increasing the binding capacity of melatonin to its receptor.

PMID- 19112898
TI  - [Effect of Astragalus mongholicus on expression of connective tissue growth
      factor in kidney of SD rats with unilateral ureteral obstruction].
AB  - OBJECTIVE: To study the effect of Astrangalus mongholicus (AM) on the expression
      of Connective Tissue Growth Factor (CTGF) in SD rats with Unilateral Ureteral
      Obstruction (UUO) and elucidate the mechanism underlying the renorotective
      effects of AM. METHODS: 36 Sprague-Dawley rats were randomly divided into 3
      groups: sham-operation group (Sham), UUO group (UUO) and UUO + AM group (AM).
      After administration of AM (10 g/kg x d) for 7 and 14 days, the dynamic
      histological changes of renal interstitial tissues were observed and renal damage
      including tubular impairment and interstitial fibrosis were quantified on HE and
      Masson stained tissue sections. The expressions of CTGF and alpha-smooth muscle
      actin (alpha-SMA) were measured by immunohistochemistry staining sections. The
      mRNA of CTGF and alpha-SMA were reversely transcribed and quantified to real-time
      PCR. The expression of CTGF protein was assessed by Western blot. RESULTS: Renal
      damage was exacerbated and the expressions of alpha-SMA and CTGF significantly
      increased in UUO group compared with those of Sham group (P < 0.05) at each time
      point. Tubular impairment and interstitial fibrosis were alleviated, and up
      regulations of expressions of CTGF and alpha-SMA were significantly depressed by
      AM treatment (P < 0.05). CONCLUSIONS: AM can ameliorate renal interstitial
      fibrosis induced by UUO in rats. The mechanism of its antifibrotic effects may be
      related to the down-regulation of CTGF expression, following suppression of
      tubulo-epithelial mesenchymal transdifferentation in renal intersitial progress.

PMID- 19112899
TI  - [Effect of shenshuaining dispersible tablets on the levels of NO, NOS, SOD and
      MDA in kidney of chronic renal failure rats].
AB  - OBJECTIVE: To observe the effect of Shenshuaining dispersible tablets on the
      levels of NO, NOS, SOD and MDA in kidney of chronic renal failure (CRF) rats
      induced by adenine. METHODS: Seventy-two Sprague-Dawley rats were randomly
      divided into 6 groups: normal control group, model control group, Niaoduqing
      group, Shenshuaining dispersible tablets group(high, middle and low dose). From
      the second to the sixth group, the rats were prepared for model of CRF by being
      fed 0.5% adenine. After giving corresponding drugs for 7 weeks, we detected the
      levels of nitric oxide (NO), total nitric oxide synthase (T-NOS), inducing nitric
      oxide synthase (iNOS), configuration nitric oxide synthase (cNOS), total
      superoxide dismutase (SOD), Cu/Zn-SOD and malonaldehyde (MDA) in every rat's
      kidney tissue. RESULTS: Compared with normal rats, CRF rats' renal tissue's
      levels of NO, T-NOS, cNOS, T-SOD and Cu/Zn-SOD markedly decreased. Both the iNOS
      and MDA contents significantly increased. Shenshuaining dispersible tablets could
      markedly ameliorate above indexes. CONCLUSION: Shenshuaining dispersible tablets
      can effectively improve CRF rats' antioxidation effect and reduce damnification
      of free radical and protect the kidney.

PMID- 19112900
TI  - [Effect of pomegranate peel extracts on oxidative stress in restrained mice].
AB  - OBJECTIVE: To observe the protective effects of pomegranate peel extracts on
      oxidative stress in restrained mice. METHODS: The liver injury model was
      established under 18 h restraint stress in mice. The protective effects were
      evaluated by assessing alanine aminotransferase (ALT) GSH and Malondialdehyde
      (MDA) levels in plasma and antioxidant capacities of liver were measured by using
      oxygen radical absorbance capacity (ORAC) assay. RESULTS: Activities of ALT and
      levels of MDA were observed to decrease on pomegranate peel extracts treated mice
      as compared with restraint stress control group and antioxidant capacity in liver
      homogenization and the levels of GSH in plasma significantly increased as
      compared with restraint stress. CONCLUSION: The results indicate that pomegranate
      peel extracts exert protective effects on oxidative stress in mice loaded with
      restraint stress, which may be related to its free radical scavenging activity
      and lipid peroxidation inhibitory effect.

PMID- 19112901
TI  - [Apoptosis and activity changes of telomerase induced by essential oil from pine
      needles in HepG2 cell line].
AB  - OBJECTIVE: To study the effects of essential oil extracted from pine needles on
      HepG2 cell line. METHODS: HepG2 cells were treated with essential oil extracted
      from pine needles. Cell growth rate was determined with MTF assay, cell
      morphologic changes were examined under transmission electromicroscope and HE
      straining. Flow cytometry was used to exmine apoptotic cells. Bcl-2 gene
      expression was determined by flow cytometry and telomerase activity by TRAP
      assay. RESULTS: Essential oils from pine needles could not only repress the
      growth of HepG2 cells significantly, but also induce apoptosis to them. Both dose
      effect and time-effect relationship could be confirmed. Typical morphology
      changes of apoptosis such as nuclear enrichment and karyorrhexis were observed
      through transmission electromicroscope and HE straining. Telomerase activity was
      down regulated in the essential oil extracted from pine needles induced apoptotic
      cells. The expression of bcl-2 gene was suppressed after the essential oil from
      pine needles treatement. CONCLUSION: The essential oil extracted from pine
      needles can inhibit cell growth of HepG2 cell line and induce apoptosis, which
      may associate with inhibition of telomerase activity and bcl-2 may be involved in
      the regulation of telomerase activity.

PMID- 19112902
TI  - [Effect of total flavones from Cuscuta chinensis on expression of Th type-1/Th
      type-2 cytokines, serum P and PR in abortion rats model].
AB  - OBJECTIVE: To study the effect of TFCC on expression of Th type-1/Th type-2
      cytokines and PR in rats abortion model, and observe the changes of serum P and
      PRL. METHODS: Early abortion rat model was established by Bromocriptine at 6-8
      gestation day, the model rats were treated with high and low dosage of TFCC and
      the progesterone as the positive control. Progesterone and prolactin levels in
      the serum were measured by radioimmunoassay, the protein expression of PR was
      inspected by immunohistochemical, RT-PCR was applied to determine the expression
      of Thl/Th2 mRNA on deciduas. RESULTS: In the deciduas of model group, IL-4 and IL
      10 cytokine contens were clearly lower than that of normal pregnancy group. The
      difference was notable(P < 0.05), In the deciduas of model group, IFN-gamma and
      TNF-alpha cytokine contents were clearly higher than that of normal pregnancy
      group. The difference was notable (P < 0.05), TFCC could up-regulate the level of
      IL-4 and IL-10, and down-regulate the level of TNF-alpha and IFN-gamma, which
      could promote P secretion and up regulate PR mRNA expression on deciduas.
      CONCLUSION: TFCC can regulate endocrinologycal and immunological network
      equilibration on maternal-fetal face, finally achieve prevention abortion.

PMID- 19112903
TI  - [Study on apoptosis of BEL-7402 cells induced by galangin].
AB  - OBJECTIVE: To investigate apoptosis of BEL-7402 cells induced by Galangin.
      METHODS: Cytotoxicity and cell viability were assayed by MT methods. Morphologic
      assessment of apoptosis was performed by fluorescence microscope, cell cycle and
      mitochondrial membrane potential were analyzed by flow cytometry, Caspases
      Activities were detected by chromogenic substrate assay. RESULTS: BEL-7402 cells
      treated with Galangin showed apparently cytotoxicity, IC50 of Galangin was 30.15
      mg/L The growth curve showed that the ratio of growth decreased with the
      increasing of concentration of Galangin. The apoptosis appeared 24 hours after
      treated with 20-80 mg/L Galangin, morphologic changes included nuclear chromatin
      condensation and fluorescence strength was observed with fluorescence microscope.
      The activity of Caspase-9 attained to peak value at 6 h, while Caspase-6 activity
      was up to peak value at 12h and Caspase-3 activity attained to peak value at 18
      h. CONCLUSION: Galangin may induce BEL-7402 cells apoptosis by mitochondrial
      pathway.

PMID- 19112904
TI  - [Curcumin inhibiting the expression of indoleamine 2,3-dioxygenase induced by IFN
      gamma in cancer cells].
AB  - OBJECTIVE: To investigate the effect of curcumin on indoleamine 2, 3 -dioxygenase
      (IDO) expression induced by IFN-gamma in cancer cells. METHODS: A431, HeLa,
      HepG2, CNE2 cells were treated with curcumin for 24 hours, then the cell
      proliferation was detected by methyl thiazolyl tetrazolium (MTF) assay. The
      effects of curcumin on IDO expression induced by IFN-gamma in these cancer cells
      were demonstrated by Western blot. The transcription of interferon responsive
      factor-1 (IRF-1), which was a key transcription factor regulating IDO expression,
      was analyzed by reverse transcription polymerase chain reaction (RT-PCR) under
      the treatment of curcumin. RESULTS: Curcumin inhibited the expression of IDO in
      these cancer cells. However, curcumin did not inhibit the transcription of IRF-1
      in cancer cells. CONCLUSION: Curcumin could inhibit the expression of IDO in
      cancer cells.

PMID- 19112905
TI  - [The effects of extracts from Arenaria kansuensis on the levels of HBsAG and
      HBeAg in HepG2.2.15 cells].
AB  - OBJECTIVE: To investigate the anti-HBV effects of the extracts with alcohol and
      water from Arenaria kansuensis in vitro. METHODS: HepG2.2.15 cells were used to
      estimate the effects of the extracts with alcohol and water from Arenaria
      kansuensis on the levels of HBsAg and HBeAg in medium by ELISA. RESULTS:
      Incubation of HepG2.2.15 cells with both the extracts with alcohol and water from
      Arenaria kansuensis (50-400 mg/L) for 72 and 96h significantly inhibited the
      levels of HBsAg and HBeAg. The maximum inhibiting rate of HBeAg from the Arenaria
      kansuensis extracts with alcohol was 63.2% and 90. 8% at 72h and 96h,
      respectively. Meanwhile, the Arenaria kansuensis extracts with water had obvious
      inhibitory effects on the levels of HBsAg and HBeAg in HepG2.2.15 cells at 96 h,
      compared with that of the control group (P < 0.01). The maximum inhibiting rates
      were 52.5% and 72.8%, respectively. CONCLUSION: The extracts with water from
      Arenaria kansuensis has obvious anti-HBV effects in vitro.

PMID- 19112906
TI  - [Research on active part of Sambucus chinensis against hepatitis mice induced by
      CCl4].
AB  - OBJECTIVE: To investigate the best extraction process of Sambucus chinensis
      against hepatitis and research on its active part. METHODS: We studied the
      protective effects of different extracts of Sambucus chinensis distilled by
      different extraction process on mice acute hepatic injury induced by CCl4, and
      searched for the active part of Sambucus chinensis against hepatitis from the
      best extract by extraction with different solvent and purification with
      macroporous adsorption resin, then studied their protective effects on mice acute
      hepatic injury induced by CCl4. RESULTS: The extraction of Sambucus chinensis by
      75% alcohol showed very significantly protective effects on mice acute hepatic
      injury induced by CCl4 and the effects were better than that of other extraction
      process. The extraction eluted by 30% alcohol after purification with macroporous
      adsorption resin and extracted by EtOAc in the extraction of Sambucus chinensis
      by 75% alcohol all showed significantly protective effects on mice acute hepatic
      injury induced by CCl4, and the effects of the extraction eluted by 30% alcohol
      after purification with macroporous adsoption resin were better than extraction
      with EtOAc. CONCLUSIONS: The best extraction solvent is 75% alcohol. The active
      part of Sambucus chinensis against hepatitis is the extraction eluted by 30%
      alcohol after purification with macroporous adsorption resin and extraction with
      EtOAc.

PMID- 19112907
TI  - [Separation and purification of proanthocyanidins from rose by macroporous
      resins].
AB  - OBJECTIVE: To study the separation and purification technology for
      proanthocyanidins from rose and establish the best operating conditions. METHODS:
      Evaluated by static adsorption capacity and elution ratio, five types of
      macroporous resins including D101, D1300, NKA, AB-8, NKA-II were tested to
      separate and purify proanthocyanidins. And evaluated by product purity, the
      concentration of extract sample, pH of extract sample, concentration of eluant
      and flow rate of elution had been investigated. RESULTS: D101 type macroporous
      resin showed the best property and was suitable for purifying proanthocyanidins
      from rose. The best operating conditions were as follows: 1.25 mg/ml as the
      concentration of extract sample, 2 as the pH value of extract sample, 70% ethanol
      equeous solution as the eluant and 2 ml/min as the flow rate of elution.
      CONCLUSION: This study can supply a method to separate and purify
      proanthocyanidins from rose.

PMID- 19112908
TI  - [Comparison study of different methods for extracting volatile oil from
      bergamot].
AB  - OBJECTIVE: To test different methods for extracting volatile oil from bergamot.
      METHODS: The determination of bergapten was carried out by RP-HPLC. Four
      different ways of organic solvent extraction, steam-input distillation,
      distillation of the material mixed with water and press extraction were compared.
      RESULTS: Bergapten wasnt extracted by ways of steam-input distillation and
      distillation of the material mixed with water. CONCLUSION: The steam distillation
      extraction can be taken to extract volatile oil from bergamot for protecting
      humans' skins.

PMID- 19112909
TI  - [Preparation and characterization of herba pogostemonis, rhizoma atractylodis and
      radix aucklandiae compound essential oil-beta-cyclodextrin complex].
AB  - OBJECTIVE: To prepare and characterize Herba pogostemonis, Rhizoma atractylodis
      and Radix aucklandiae compound essential oil-beta-cyclodextrin complex. METHODS:
      The essential oil-p3-cyclodextrin complex was prepared by colloidal mill method.
      TLC, XRD, DSC and TGA analysis were applied to characterize it. RESULTS: The
      complex inclusion rate of essential oil-beta-CD complex was 82.4%, and the
      complex recovery was 80.7%. The formation of essential oil-beta-CD complex was
      proved by the results of TLC, XRD, DSC, TGA analysis. CONCLUSION: The stability
      of compound essential oil is improved by the preparation of oil beta-cyclodextrin
      complex.

PMID- 19112910
TI  - [Pay attention to diagnosis and treatment of complications after hematopoietic
      stem cell transplantation].

PMID- 19112911
TI  - [Clinical contrasting study on hematopoietic stem cell transplantation from HLA
      identical sibling and partially HLA-mismatched related donors].
AB  - OBJECTIVE: To explore the therapeutic feasibility of allogeneic hematopoietic
      stem cell transplantation (allo-HSCT) from partially HLA-mismatched related
      donors for hematologic diseases. METHODS: Thirty patients with hematologic
      diseases received allo-HSCT from 1 - 3 loci mismatched related donors
      conditioning regimen consisting of ATG (thymoglobulin, total dose of 10 mg/kg,
      intravenously on - 4 d to - 1 d), and only 5 (18%) of 28 recipients from HLA
      identical sibling donors were treated with regimen containing ATG. Donors were
      given G-CSF prior to hematopoietic stem cell harvest and CsA, short-term MTX and
      mycophenolate mofetil (MMF) were used for GVHD prophylaxis in both group.
      RESULTS: All patients were successfully engrafted. There was no significant
      difference in the incidence of grade II to IV acute graft-versus-host disease
      (aGVHD) and grade III to IV aGVHD between the mismatched and matched groups (34%
      vs 32%, and 13% vs 11%, respectively). 3-year overall survival (OS) and disease
      free survival (DFS) in mismatched and matched groups were 57% vs 77% (P = 0.14)
      and 57% vs 69% (P = 0.28), respectively. Multivariate analysis showed that
      advanced disease pre-transplant (P = 0.006) and CMV infection (P = 0.04) were
      risk factors for OS. OS for patients with stable disease in mismatched and
      matched groups were 87% vs 81% (P = 0.65) respectively, and for those with
      advanced disease were 21% vs 71% (P = 0.02). CONCLUSIONS: It is feasible to
      perform allo-HSCT from 1 -3 loci HLA-mismatched related donors for patients with
      stable disease who lack HLA-identical sibling donors. Nevertheless, for patients
      with advanced disease optimized conditioning regimen and intensive supporting
      therapy should be administered to obtain better clinical outcomes.

PMID- 19112912
TI  - [CD34 cells and T cell subsets in recombinant human granulocyte colony
      stimulating factor primed bone marrow grafts from donors with different
      characteristics].
AB  - OBJECTIVE: To investigate the cell composition in granulocyte colony-stimulating
      factor One (rhG-CSF) primed bone marrow grafts (G-BM) from donors with different
      characteristics. METHODS: hundred and fifty healthy donors were injected
      subcutaneously rhG-CSF (5 microg x kg(-1) x d(-1)) in five consecutive days. Bone
      marrow and peripheral blood stem cells were harvested at day 4 and day 5. The
      number of CD3, CD3+ CD4+, CD3+ CD8+, CD14+ , CD34+ and CD3+ CD4- CD8- cells were
      determined by multicolor flow cytometry. Cell composition of G-BM from donors
      with different characteristics, including sex, age, weight, pregnancy were
      analysed. RESULTS: The absolute number of nuclear cells (NCs), lymphocytes, CD3+,
      CD3+ CD4+, CD3+ CD8+, CD14+, CD34+ and CD3+ CD4- CD8- cells in G-BM were 31 050
      (12 200 -58 100), 2122 (506 - 6618), 1344 (307 - 4791), 692 (145 - 3038), 616
      (112 - 2575), 986 (265 -2958), 63 (11 -505) and 83 (9 -390) per microliter,
      respectively. The number of NCs [33 800 (18 600 - 57 100)], CD34+ cells [76 (22 
      505)], and CD3+ CD4+ CD8- regulatory T cells [97 (11 - 380)] harvested from
      younger donors (aged < or = 38 years) were significantly higher than those from
      older ones (aged > 38) [28000 (12200-58100), 49 (11-220), and 65 (9 - 389) per
      microliter (P = 0.027, < 0.001 and = 0.001, respectively)]. Compared with that in
      donors with peripheral blood monocytes (PBMs) < or = 0.37 x 10(9)/L, higher
      number of NCs in G-BM [27 150 (13 800 - 58 100) vs 33 550 (12 200 - 57 100), P =
      0.005] were collected in donors with PBMs > 0.37 x 10(9)/L. Multivariate analysis
      showed that donors age (< or = 38 vs > 38 years; P = 0.01) and monocyte number in
      peripheral blood (< or = 0.37 x 10(9)/L vs > 0.37 x 10(9)/L; P = 0. 003) were
      factors predicting for NC yields, and donors age ( < or = 38 vs > 38 years; P <
      0.001) was factor predicting for yields of CD34+ cells (P < 0.001) and CD3+ CD4-
      CD8- regulatory T cells (P = 0.001) collection. CONCLUSION: Donor age is a factor
      for the yields of NCs, CD34+ cells, and CD3+ CD4- CD8- regulatory T cells
      collection in G-BM, and donor's PBMs more than 0.37 x 10(9)/L, is another factor
      affecting NCs harvests.

PMID- 19112913
TI  - [Allogeneic hematopoietic stem cell transplantation following reduced intensity
      conditioning regimen for treatment of refractory leukemia].
AB  - OBJECTIVE: To evaluate the efficacy of allogeneic hematopoietic stem cell
      transplantation (allo-HSCT) following reduced intensity conditioning (RIC)
      regimen for treatment of refractory leukemia. METHODS: Twenty patients with
      refractory leukemia received allo-HSCT following RIC regimen consisting of
      fludarabine plus small or moderate dose total body irradiation (TBI). Graft
      versus host disease (GVHD) prophylaxis was CsA plus mycophenolate mofetil (MMF)
      or short-term MTX, or these three drugs combination; CD25 monoclone
      antibody(McAb) and ATG were also used in some of the patients. RESULTS: Seventeen
      patients engrafted successfully, the median time for ANC > 0.5 x 10(9)/L was 13
      (11 - 17) days, and for BPC > 50 x 10(9)/L 19 (12 -42) days. Detected by short
      tandem repeat (STR)-PCR, complete donor chimerism was confirmed in 16 patients
      with a median of 14 (7 -35) days. The incidence of acute and chronic GVHD was
      47.1% (8/17) and 38.5% (5/13) respectively. The transplant related mortality
      (TRM) was 25.0% (5/20), mainly from graft failure, intracranial hemorrhage and
      severe infection. Up to now, 7 patients relapsed and 9 were alive with leukemia
      free. The overall survival (OS) at 2 year was (35. 3 +/- 14.2)% for all patients
      and (52.5 +/- 18.6)% for acute non-lymphocytic leukemia (ANLL) patients.
      CONCLUSION: Allo-HSCT following fludarabine and TBI based RIC regimen can be used
      for treatment of refractory leukemia with well tolerance and low TRM and there is
      a better prognosis for ANLL patients than that for acute lymphocytic leukemia
      patients.

PMID- 19112914
TI  - [The significance of serial monitoring of bcr-abl transcripts levels after
      allogeneic hematopoietic stem cell transplantation in screening chronic myeloid
      leukemia patients with low relapse].
AB  - OBJECTIVE: To explore dynamic status of bcr-abl transcript levels in chronic
      myeloid leukemia (CML) patients after allogeneic HSCT and to define low relapse
      patients who may not require further therapeutic intervention. METHODS: One
      hundred and forty-nine CML cases received allo-HSCT at our Institute between Nov.
      2004 and Nov. 2006. Bcr-abl transcripts levels were monitored from bone marrow
      samples by Q-RT-PCR in all cases pre-HSCT and at 1, 2, 3, 4, 5, 6 months post
      HSCT. The median value of bcr-abl at these time points were calculated and
      compared by Mann-Whitney U test. The relapse rate, overall survival (OS) and
      incidence of graft versus host disease (GVHD) were calculated by Kaplan-Meier
      curve. RESULTS: All cases engrafted. 2-year OS rate was 86.0% (CI: 82.9% -89.1%),
      2-year accumulated hematological relapse rate (RI) was 3.5% (CI: 1.7% -5.3%). 102
      cases were not received any further intervention and none of them relapsed. The
      median value of bcr-abl transcripts was 25.800% (CI: 0.067% - 96.100%) pre-HSCT
      and 0.025% (CI: 0 - 3.583%) at +30 d, 0.011% (CI: 0-0.425%) at +60 d, 0.002% (CI:
      0 - 0.610%) at +90 d, 0 (CI: 0 - 0.056%) at +120 d post HSCT. The bcr-abl mRNA
      levels decreased to undetectable level at +3 m, +4 m, and +5 m in recipients from
      HLA-mismatched related donor, identical sibling donor and unrelated donor
      respectively. CONCLUSIONS: Serial monitoring of bcr-abl transcript levels by real
      time quantitative PCR after allo-HSCT is helpful for screening CML patients with
      low risk of relapse.

PMID- 19112916
TI  - [Experimental study on the effect of sensitized sera on engraftment of
      hematopoietic stem cells].
AB  - OBJECTIVE: To evaluate the effect of sensitized sera on engraftment of
      hematopoietic stem cells (HSCs) and its mechanism. METHODS: Bone marrow cells
      (BMCs) from C57BL/6 mice were incubated with sensitized sera (group I) or normal
      sera (group II), and then washed and transplanted into irradiated BALB/c mice.
      The survival analysis and engraftment evaluation of the recipients were observed.
      The incubated BMCs were bound with goat anti mouse IgG for and labeled with
      Annexin V for apoptosis detection. RESULTS: Seven out of ten recipient mice in
      group I died of bone marrow failure at day 10 after transplantation, while all of
      those in group II were long-term survived. Engraftment assay showed recipients
      blood count and BMCs progressively decreased along with time passing in group I;
      in addition, the chimeric percentage of donor cells progressively decreased as
      well. The percentage of BMCs binding with goat anti mouse IgG in group I or group
      II were (90.3 +/- 5.1)% and (5.2 +/- 2.4)%, respectively, and the difference was
      statistically significant (P < 0.01). However, no significant difference was
      found in the apoptosis detection between the two groups (P > 0.05). CONCLUSION:
      The engraftment capacity of HSCs is significantly impaired by sensitized sera,
      the antibodies in sensitized sera may bind to antigens expressed on HSCs but do
      not induce apoptosis.

PMID- 19112915
TI  - [Experimental study on IL-2- and IL-15 application in allogeneic hematopoietic
      stem cell transplantation].
AB  - OBJECTIVE: To explore the impact of IL-2- and IL-15-activated donor natural
      killer (NK) cell infusion on graft-versus-host-disease (GVHD) and graft-versus
      leukemia (GVL) effect post allogeneic hematopoietic stem cell transplantation
      (allo-HSCT). METHODS: The C57BL/6 mice splenic NK cells were selected by
      microbeads, and then expanded in the media containing IL-2 and IL-15. The killing
      activity of NK cells was detected. In the leukemia mouse model, recipients
      (BALB/c) were intravenously inoculated with EL9611 leukemia cells 8 days before
      transplantation. Lethally irradiated BALB/c recipient mice were transplanted with
      5 x 10(6) bone marrow cells (BMCs), or 5 x 10(6) BMCs plus 1 x 10(7) splenocytes
      with or without 1 x 10(7) activated NK cells. Additionally, NK cell infusion
      group mice were intraperitoneally injected with a mixture of IL-2 and IL-15 post
      transplant. Survival time, GVHD occurrence, lineage chimerism, TRBV spectra
      typing were observed post transplant. RESULTS: The purity of isolated splenic NK
      cells was 95.7% - 97.1%. The killing activity of NK cells after activation was
      increased by 3 times. GVHD did not occurred in allogeneic BMCs infusion group,
      whereas did from 1 week after transplant in allogeneic BMCs + splenocytes
      infusion group. The severity of GVHD in total body irradiation (TBI) experimental
      group was significantly lower than in splenocytes infusion group (P < 0.05). The
      survival time was 9.5 - 14.0 d in TBI alone conditioning group. In leukemia mouse
      model, 100 day survival rate was 10% the rest of them were died of leukemia while
      in experimental group, the more than 100 days survival rate was 80% (P < 0.01).
      PB NK cells at 2 week post-transplant were 4.8% in experimental group and 2.8% in
      control group. NK cells recovery in experimental group was earlier than that in
      control group (P < 0.05). TRBV reconstitution was faster in experimental group
      than in control group, moreover, the number of TRBV family expression was more in
      experimental group than in control group which mainly expressed monoclone or
      oligo-clone. CONCLUSIONS: Donor alloreactive NK cells can be efficiently expanded
      and activated with IL-2 and IL-15. Donor activated NK cell infusion and IL-2, IL
      15 treatment can promote immune reconstitution, mitigate GVHD and reduce leukemia
      relapse.

PMID- 19112917
TI  - [The expression of basic fibroblast growth factor 1 during human embryonic yolk
      sac hematopoiesis].
AB  - OBJECTIVE: To explore the effect of basic fibroblast growth factor 1 (bFGF1)
      during embryonic development on hematopoiesis, to study the expression of FGF1,
      vascular endothelial growth factor receptor (KDR), CD133, CD34 and transcription
      factors Ihh, SCL, GATA-1, GATA-2 and PU. 1 in the yolk sac, and to learn about
      the role and relationships of FGF1, hematopoietic cells and transcription factors
      during embryonic hematopoiesis. METHODS: 10 microm sections and total RNA were
      prepared from 107 human embryos aged 3-12 weeks. Immunohischemical SP staining
      and RT-PCR were performed. RESULTS: The yolk sac blood islands of human 3
      approximately 12 weeks embryos consisted of peripheral vascular endothelial cells
      and central hematopoietic cells. The expression of FGF1 was firstly found in
      visceral mesoderm around periphery of yolk sac blood island at day 16, while was
      little inside it. KDR was not or lowly expressed and CD34 and CD133 were not
      expressed then. The expression increased, gray value decreased and staining
      enhanced at day 21. Strong staining of CD34+, CD133+ and KDR+ cells were found in
      blood island and mesoderm at day 30, their gray values changed from 156 +/- 16,
      173 +/- 18 and 160 +/- 14 to 53 +/- 7, 52 +/- 6 and 69 +/- 8 respectively. FGF1
      expression was strong positive, the gray value declined dramatically from 161 +/-
      13 to 40 +/- 5. Some positive cells formed vessel-like structure along the
      periphery of blood island. Moderate expression of CD34+, CD133+, KDR+ cells
      increased at day 45, the cells aggregated into mass in blood island and FGF1+
      cells did the same in blood island, while little in mesoderm. Its gray valve was
      increased. After 7 weeks, CD133+, KDR+, CD34+ cells significantly decreased their
      gray values increased, the staining became week. FGF1 was weakly expressed in
      yolk sac and its gray value increased to 179 +/- 22. RT-PCR showed Ihh, SCL, GATA
      1 and GATA-2 were expressed at different time in yolk sac. PU. 1 were not
      expressed at day 16, and then expressed. CONCLUSIONS: The hematopoietic
      properties of yolk sac may be dependent on signaling through FGF receptors and
      FGF1 plays an important role in hematopoietic stem cell homeostasis. The FGF
      pathway regulates primitive hematopoiesis by modulating transcription factors
      such as Gata1 expression level and activity.

PMID- 19112918
TI  - [Experimental study on influence of bone marrow mesenchymal stem cells on
      activation and function of mouse peritoneal macrophages].
AB  - OBJECTIVE: To explore the influence of bone marrow (BM) mesenchymal stem cells
      (MSCs) on macrophage activation after lipopolysaccharide (LPS) stimulation.
      METHODS: Mouse BM MSCs were isolated and purified by adherence screening, and
      mouse peritoneal macrophages (MPM) were collected by sodium thioglycollate
      peritoneal injection, and the co-culture system was established by planting
      macrophages on the MSCs monolayer. The grouping of experiments: group A: MPM;
      group B: MPM + LPS; group C: MPM + LPS + MSC; group D: MPM + LPS + MSC
      supernatant. Cell culture supernatants were collected to detect the changes of
      TNF-alpha/TGF-beta and nitrogen monoxide (NO) after stimulating macrophages with
      LPS for 18 hours. At the same time Escherichia coli standard strain (ATCC25922)
      was added into the culture system and incubated for another 24 hours, macrophages
      were stained and phagocytosis were examined. RESULTS: The concentrations of TNF
      alpha and NO in culture supernatants were increased significantly to (147.4 +/-
      37.1) pg/ml and (59.9 +/- 8.7) micromol/L respectively after macrophage
      activation, however, at the present of MSC, the concentration of TNF-alpha was
      dramatically decreased [(97.6 +/- 30.3) pg/ml, P = 0.032], and the concentration
      of NO was decreased to (50.9 +/- 29.5) micromol/L (P > 0.05). The concentrations
      of TNF-alpha and NO were further decreased after addition of MSC supernatants
      [(58.3 +/- 31.5) pg/ml and (-3.4 +/- 2.3) micromol/L respectively, P < 0.01].
      There was no change in the phagocytic rate and phagoindex of macrophages after
      activation. CONCLUSIONS: MSCs can inhibit the activation of mouse peritoneal
      macrophages after stimulating with LPS but has no influence on the phagocytosis.

PMID- 19112919
TI  - [The expression of midkine in acute leukemia and its significance].
AB  - OBJECTIVE: To analyze the expression of midkine (MK) gene in acute leukemia
      patients, and explore the relationship between the gene and leukemia. METHODS:
      The MK gene expression levels were detected by real-time quantitative RT-PCR (RQ
      RT-PCR) in bone marrow (BM) of 181 acute leukemia (AL) patients and 31 normal
      controls. RESULTS: MK gene was expressed in all AL patients, normal controls and
      AL patients in complete remission (CR). Compared with that in control group and
      CR group, MK gene expression was significantly increased in AL patients (P < 0.01
      and P < 0.05, respectively). No statistical difference was found between CR group
      and control group. The expression of MK showed a notable increase in all B-ALL
      subtypes (including pro-B-ALL, common-B-ALL and pre-B-ALL) as well as in adult
      and childhood B-ALL patients (P < 0.01). Moreover, the gene expression in B-ALL
      was also significantly higher than that in TALL, HAL and FAB subtypes of AML (P <
      0.01). In addition, M2 patients showed significantly increased in MK expression
      compared with that in normal controls (P < 0.01) and in other FAB subtypes of AML
      (P < 0.05). Median MK expression level in M3 patients was also significantly
      higher than that in normal controls (P < 0.05), but there was no statistical
      difference between M3 and other AL subtypes excepting for M2 and B-ALL. MK
      expression in CD34 positive patients was significantly higher than that in CD34
      negative ones (P < 0.01) and within M2 patients, MK expression was higher in
      patients with t (8 ;21) than in those without the translocation (P < 0.05).
      CONCLUSION: MK gene expression is increased with different levels in B-ALL, M2
      and M3 patients, which provides novel insights into the leukemogenesis of acute
      leukemia.

PMID- 19112920
TI  - [Enhancive effect of HMGB1 gene silence on adriamycin-induced apoptosis in
      K562/A02 drug resistance leukemia cells].
AB  - OBJECTIVE: To investigate the effect of high mobility group boxl (HMGBI) gene
      silence on adriamycin (ADM)-induced apoptosis in K562/A02 drug resistance
      leukemia cells. METHODS: K562/ A02 cells were transient transfected with HMGB1-
      small interference RNA(siRNA) vector, and the levels of HMGB1 gene differential
      expression pre-and post-transfection were measured by RT-PCR and Western
      blotting. 50% inhibition concentration (IC50) of ADM on K562/A02 was determined
      by WST-8 assay. Cell apoptosis was assessed by flow cytometry. The release of
      Smac/DIABLO from the mitochondria to the cytoplasm was assayed by Western
      blotting. Activity of Caspase-3 was assayed with a Caspase Colorimetric Assay
      Kit. RESULTS: (1) The HMGB1 expression at mRNA and protein levels in HMGB1 siRNA
      transfected K562/A02 cells were decreased by 86% and 71% respectively compared
      with control. (2) Suppression of HMGB1 by siRNA in K562/A02 cells resulted in a
      reversal of the resistance to ADM, and decreased IC50 from (4.83 +/- 0.08)
      microg/ml to (1.33 +/- 0.10) microg/ml. 1 microg/ml and 5 microg/ml of ADM
      treatment increased cell apoptotic rate by 27% and 32% respectively. (3) HMGB1
      suppression in K562/A02 cells significantly promoted ADM- induced Smac/DIABLO
      release from the mitochondria to the cytoplasm, and increased the activities of
      Caspase-3. CONCLUSION: HMGB1 gene silence can enhance sensitivity of K562/A02
      cells to ADM and reverse cell resistant to ADM.

PMID- 19112921
TI  - Reflections on the Australia 2020 summit long-term national health strategy.

PMID- 19112922
TI  - Insights on end-of-life ceremonial practices of Australian Aboriginal peoples.
AB  - The ceremonies surrounding death are extremely important to Aboriginal peoples
      and take precedence over all other activities. This article presents research
      findings on Aboriginal mortuary ceremonies in the hope that it will be useful for
      non-indigenous nurses working with Aboriginal peoples. A qualitative research
      methodology was used, whereby data were collected by conducting 72 open-ended
      interviews with patients, carers, Aboriginal health care workers, health care
      workers and interpreters in four geographical areas in the Northern Territory. A
      descriptive phenomenological approach was taken to the recording and analysis of
      the data. The findings reveal that traditional practices including the smoking
      ceremony (a spiritual ritual conducted in the deceased's living space with the
      rationale of driving the deceased's spirit away), painting ochre on all living
      spaces inhabited by the deceased, or alternatively of putting up "flags" (which
      is considered to drive away the deceased's spirit and also to notify to the
      community that this is the house of a deceased) and the death ceremony (which
      includes practices such as keeping the deceased's body in the home, painting the
      bodies of the mourners and bringing kinship communities together to share food,
      song and dance) are of great significance in many Aboriginal cultures. It is the
      authors' hope and expectation that an understanding of these rituals, and their
      significance for different cultural groups, will assist nurses by increasing
      their knowledge of Aboriginal cultural and ceremonial practices associated with
      caring for the deceased and so aid their important work in this area.

PMID- 19112923
TI  - Nurses in the clinical area: relevance of a PhD.
AB  - This project aimed to explore the application and relevance of a PhD to nurses
      working in the clinical area. The complexity of nursing practice requires
      clinical nurses to be competent as investigators and professional leaders who
      could help structure nursing practice in more efficient ways. Research proposes
      that a PhD offers Limited employment opportunities, is mainly research oriented
      and tends to direct a nurse away from the clinical field. A mixed method study
      design utilising surveys and interviews was chosen to collect data for this
      study. Participants were nurses with a doctoral degree working/having worked in a
      clinical area after obtaining their PhD Nurses were recruited through student
      databases from Australian universities that offer doctoral degrees in nursing and
      also by using a snowball sampling technique. The majority of the 19 nurses who
      participated in the study had: varied expectation of doing a PhD; maintained
      their clinical positions after obtaining their doctoral degree, considered that
      the degree helped them to obtain better jobs/promotions and acknowledged the
      value of the PhD in patient care, in improving research and informing health
      policy. This study has exposed the positive aspects of completing a PhD and
      identifies its constructive application in the clinical area. It is essential to
      provide support and opportunities for nurses working in the clinical area to
      pursue doctoral degrees in order to enable them to enhance knowledge and build
      confidence and leadership skills and contribute to the improvement of nursing
      practice and the continued development of the profession.

PMID- 19112924
TI  - Beyond barriers. The challenge of cultural diversity for nurse academics in the
      Australian context.
AB  - In spite of the increasing significance of cultural diversity for nursing, some
      Australian nurse teachers are not well prepared for the challenges they face, nor
      have nursing curricula been re-conceptualized to meet the changing needs of
      society and more specifically nursing students. Although numerous teaching and
      Learning programmes for inclusion of diversity are reported in the literature,
      both within Australia and overseas, there appears to be little commitment to the
      adoption of a more fundamental change in curricula and teaching and learning
      practices. In particular there appears to be little attention to how teachers
      negotiate meaningful social dynamics within multicultural learning contexts. This
      article reports on the findings of a study carried out across two Schools of
      Nursing in Australia. The purpose of the study was to explore why schools have
      been reluctant to move to more culturally diverse models of teaching and
      learning. This paper reports on the findings of focus groups with teachers about
      their experiences of teaching in the context of cultural diversity. Study
      findings explore teachers' perceptions of cultural diversity and its impact on
      teaching and learning nursing. Teachers reported a range of tensions arising from
      lack of a shared philosophical view about curricula generally, lack of
      consideration of diversity as a significant issue for both teachers and students,
      limited perceptions of community as a key driver of curricula and a reluctance to
      address the difficult and contentious issues arising from diversity in the
      classroom.

PMID- 19112925
TI  - The palliative care clinical nurse consultant: an essential link.
AB  - This study describes the role of acute hospital palliative care nurse consultants
      and makes recommendations about future directions for the role development of
      this role. While the palliative care nurse consultant role is accepted in the
      acute setting there is little evidence or literature about what contributes to
      the success of this role. A three-phase study was undertaken to describe the role
      of palliative care nurse consultants in acute hospitals in Melbourne, Australia.
      The first phase of the three-phase study, involving in-depth qualitative
      interviews with the palliative care nurse consultants, is reported in this
      article. Using open-ended semi-structured questions, 10 palliative care nurse
      consultants were interviewed using open-ended questions about aspects of their
      role and the interviews were thematically analysed. Four main themes were
      identified that clarified the role; being the internal link; being the lynch pin;
      being responsive and being challenged. The palliative care nurse consultants were
      the first point of introduction to palliative care and thus they saw a
      significant role in introducing the concept of palliative care to those requiring
      palliative care, their families and others. They are an important link between
      the settings of care required by people accessing palliative care-acute, in
      patient palliative care and community care. The palliative care nurse consultants
      saw themselves in leadership positions that in some ways defy boundaries, because
      of the inherent complexity and diversity of the role. The palliative care nurse
      consultants' role appears to be pivotal in providing expert advice to staff and
      people requiring palliative care, and connecting palliative care services both
      within the hospital and to external services.

PMID- 19112926
TI  - Effect of a residential respite admission for older people on regional Queensland
      family carers.
AB  - OBJECTIVE: This study undertaken in regional Queensland aimed to determine the
      effect of a residential respite care (RRC) admission for older people on family
      carers. METHOD: The study used a repeated measures, prospective design. The
      participants were 100 family carers and their older dependants who were studied
      before and after the RRC admission. RESULTS: Family carer psychological distress
      increased after a period of RRC [F(1, 57) = 250.9, p < .001] as did the level of
      caregiver burden [F(1, 57) = 189.8, p < .001]. The presence of dementia and
      hearing problems in the RRC recipients, the psychological distress of the family
      carer, being younger and a spouse of the RRC recipient all predicted carer
      burden. CONCLUSIONS: It is not surprising that RRC, once over, does not
      necessarily reduce psychological distress and carer burden if this is associated
      with ongoing caring responsibilities that are resumed after RRC. Nurses need to
      discuss these issues with family carers and inform them of the likely outcomes of
      RRC and how they may better utilise the 'break' provided by RRC to counteract
      some of this response.

PMID- 19112927
TI  - The evolution of palliative care and the relevance to residential aged care:
      understanding the past to inform the future.
AB  - Improving the experience of dying in residential aged care units became a
      significant project of the Australian Government's National Palliative Care
      Program in 2004. This initiative resulted in an expectation that residential aged
      care facilities would adopt the recommended palliative approach to underpin
      service delivery. Recognising palliative care as a specialist area of health care
      practice is a recent development which has influenced the expectations of
      community and government. This paper traces the global history of palliative care
      and how historical factors influenced its development in Australia. This
      discussion presents an overview of the positioning of dying and death within
      society, explaining how with the shifting emphasis on care of the dying
      accordingly has been the focus on palliative care specialists. Care of the dying
      in residential aged care units has largely been overlooked in the context of
      specialist involvement. This paper acknowledges dying and death as occurring in
      residential aged care facilities, illuminating the advantages of adopting a
      palliative approach and offers recommendations.

PMID- 19112928
TI  - A quantitative expression of resiliency in the workplace: an odds ratio analysis.
AB  - This paper reviews four empirical investigations into the effectiveness of
      workplace-based crisis intervention programs designed to enhance psychological
      resiliency. As an extension of a previously published review of effect sizes of
      workplace-based crisis interventions (Everly et al., 2006), this paper extends
      the expression of intervention effectiveness by proposing, then utilizing, the
      odds ratio statistic. It is proposed that the odds ratio is a more useful tool by
      which to express the practical utility of workplace-based psychosocial
      interventions. Thus, the use of odds ratios may be a tool that serves to ease the
      translation of research into practice. That is, odds ratios may aid in expressing
      the potential usefulness of workplace-based crisis intervention programs in terms
      that can be easily understood by program managers and policy makers without
      extensive training in inferential statistics, thereby potentiating increased
      utilization of such programs as indicated.

PMID- 19112929
TI  - Characteristics of four types of patient assaults: fifteen-year analysis of the
      Assaulted Staff Action Program (ASAP) with EMS implications.
AB  - Thirty years of empirical research have documented the recurring risk of assault
      by psychiatric patients on emergency services and health care providers. Most
      studies have reported all patient assaults in the aggregate. However six studies
      that have reported physical assault, sexual assault, nonverbal intimidation, and
      verbal threats as separate categories have reported significant patient/staff
      victim differences in characteristics by category. This 15-year retrospective
      study examined patient assaults and their impact by four standard assault
      categories. Similarities and differences across assault categories are presented
      Methodological issues and the safety implications for emergency services are
      discussed.

PMID- 19112930
TI  - Cognitive-affective resilience indicia as predictors of burnout and job-related
      outcome.
AB  - Resiliency has emerged as a critical construct in areas as far ranging as child
      development to disaster mental health. Resiliency may be thought of as the
      ability to rebound, or bounce back, from adversity (Kaminsky, McCabe, Langlieb, &
      Everly, 2007). Numerous interventions have been postulated and/or shown to
      enhance resiliency, e.g., journaling, social support, psychological first aid,
      and formal crisis intervention systems, such as Critical Incident Stress
      Management. As the search to develop more efficient and effective resiliency
      enhancement interventions continues, it becomes important to search for the
      mechanisms of action that actually serve to account for the ability to rebound
      after adversity. One such postulated mechanism is that of positive emotionality.
      Positive emotionality may be thought of as the presence of ambient positive
      emotions, as well as the ability to express positive emotions in the wake of
      adversity. Constructs such as confidence, optimism, and the ability to find
      meaning may underlie such expressions. This investigation attempted to assess the
      relationship between the expression of ambient emotions (within the last few
      weeks) upon measures of burnout, job satisfaction, perceived performance, and
      intention to leave one's job. This study represents a randomized sample of 2,500
      out of approximately 91,333 potential subjects. Four hundred eighty-nine and four
      hundred ninety-one usable responses were received for inclusion in the analyses.
      Correlational analyses revealed that expressed positive emotions, as well as
      expressed negative emotions, were related to the outcome variables in a
      significant but complementary manner.

PMID- 19112931
TI  - Characteristics of patients in restraint: fifteen-year analysis of the Assaulted
      Staff Action Program (ASAP) with EMS implications.
AB  - Research on the demographic and precipitant characteristics of restrained
      patients has documented that younger male/female patients diagnosed with
      schizophrenia, affective disorder, or personality disorder are at risk of being
      restrained when acutely psychotic or confronted with excess sensory stimulation
      or denial of services. However many patients with these same characteristics are
      not restrained Thus, these variables have yielded little predictive power. This
      study compared restrained/nonrestrained subjects on the demographic, precipitant
      variables and added three clinical variables (past violence to others, personal
      victimization, and substance use disorder) to assess the possible predictive
      power of clinical variables. Demographic and precipitant variables were similar
      to previous research findings. Violence toward others in combination with
      personal victimization was associated with higher restraint usage. The
      implications of the findings for emergency services are outlined.

PMID- 19112932
TI  - A short guide to giving bad news.
AB  - Approaching an individual or a family with bad news, but without an appropriate
      plan to present the information in a structured manner, is almost a guarantee of
      greater emotional pain and disruption for the recipients of the news. Crisis
      interveners must develop a strategic plan for the announcement of bad news. That
      plan should entail a lead-up phase, a transmission phase, and a followup phase.
      The lead-up phase encompasses the gathering of accurate, verifiable information
      and the clear identification of the targets of the information. The transmission
      phase includes immediate preparation for the presentation of the information, the
      actual announcement, and the presentation of additional details as questions
      arise. The follow-up phase includes a range of supportive interventions to assist
      people in the immediate crisis reaction. It also includes a system of referrals
      for people who might benefit from additional professional care. This article
      provides practical guidelines for providing bad news to the loved ones of
      injured, ill, or deceased people.

PMID- 19112933
TI  - Juror stress: symptoms, syndromes, and solutions.
AB  - As civic duties go, jury service can be among the most stressful experiences that
      a citizen can undergo. This article describes the common sources of juror stress,
      including jury summons, jury selection, understanding and coping with complex or
      disturbing evidence and testimony, jury deliberation, and the pressure to arrive
      at a just verdict. The article then goes on to delineate a number of intervention
      models for helping jurors manage stress reactions and prevent the development of
      more serious traumatic stress syndromes. Finally, some recommendations are
      offered for professionalizing jury service that would act in the interests of
      civil and criminal justice.

PMID- 19112934
TI  - A systematic, integrated behavioral health response to disaster.
AB  - The behavioral health aspects of disaster have not historically been addressed as
      a priority in emergency preparedness planning. The overwhelming evidence of
      significant to severe psychological consequences of disaster has remained in the
      shadows compared to the more widely televised dramatic physical destruction and
      trauma. However, the aftermath of September 11, as well as 2005's Hurricane
      Katrina and 2008's Hurricane Ike disasters reminded the country that the
      psychological footprint of disaster easily dwarfs the more visual physical
      footprint. Disaster behavioral health is now recognized as a major public health
      concern and a national issue that deserves a logical, systematic, proactive
      approach within the structure of the National Incident Management System (NIMS)
      and Incident Command Structure (ICS; Fojt, Cohen, Wagner 2008). With increased
      commitment, collaboration, and organization we can better utilize our qualified
      yet limited behavioral health resources, meeting the predictable needs of future
      disasters' survivors, communities, and responders.

PMID- 19112935
TI  - Cholesterol and cholesterol-rich membranes in prostate cancer: an update.
AB  - Cells maintain normal structure and function by responding appropriately to cues
      from the surrounding milieu. Extracellular stimuli are transduced from the
      surface through the plasma membrane by a complex series of interactions between
      ligands, their receptors and intracellular signaling partners (e.g., kinases, G
      proteins). Cholesterol-enriched membrane microdomains, generally referred to as
      "lipid rafts", exist within the lipid bilayer of all mammalian cells and play an
      important role in signaling from the cell surface to various subcellular
      compartments. Lipid rafts have also been implicated in tumor growth and
      aggressiveness. Epidemiological evidence suggests that the modern Western diet,
      which contains substantial levels of cholesterol and other fatty substances,
      promotes prostate cancer progression. Consistent with this idea, prolonged
      inhibition of the cholesterol synthesis pathway by pharmacologic intervention in
      men has recently been associated with reduction in risk of advanced prostate
      cancer. In this review, we discuss the possibility that membrane cholesterol
      promotes prostate cancer progression by a mechanism that involves dysregulation
      of lipid raft-resident signaling complexes. This hypothesis provides new avenues
      for mechanistic studies as well as therapeutic intervention.

PMID- 19112936
TI  - Cancer mortality in Italy, 1970-2002.
AB  - AIMS AND BACKGROUND: To update previous work on Italian cancer mortality.
      METHODS: WHO data were used to calculate death rates for 30 cancer sites for
      2002. Trends were analyzed with joinpoint regression over the 1970-2002 period.
      RESULTS: Total cancer deaths for 2002 in Italy were 163,070 (93,398 men, 69,672
      women). Male cancer mortality rose until 1988 and since then has had a 1.4%
      yearly fall. The first cause of cancer death in males was lung cancer, accounting
      for 28% of deaths. The decrease in mortality from male lung cancer came about the
      end of the 1980's (estimated annual percentage change, EAPC, -1.26 from 1989 to
      1993 and -2.32 thereafter) and was the main reason for the favorable trends in
      total male cancer mortality, reflecting the change in smoking prevalence in
      Italian males. Female total cancer mortality trends have also been favorable,
      with an overall yearly drop of 1.1% since 1992. The most frequent causes of
      cancer deaths in females were breast and colorectal cancers, accounting for 16%
      and 14% of cancer deaths, and both showed declining trends (EAPC, -1.80 since
      1992 and -1.51 from 1993 for breast and colorectal cancers, respectively). Female
      lung cancer has been on the rise (EAPC, 0.82 since 1987) for the last decades due
      to the rise in cigarette smoking since the 1970's in Italian females. DISCUSSION:
      Mortality from the most common cancers in Italy showed a favorable trend over
      recent years, the maintenance and potential improvement of which would require a
      strategy focusing on the control of tobacco and alcohol consumption, nutrition
      and diet. Early diagnosis for selected neoplasms can also have a relevant impact,
      together with advancements in treatments.

PMID- 19112939
TI  - Carboplatin and oral cyclophosphamide combination after temozolomide failure in
      malignant gliomas.
AB  - BACKGROUND: Temozolomide is a novel cytotoxic agent for malignant gliomas.
      However, treatment failure occurs approximately in half of patients, and the
      optimal regimen in this setting has yet to be defined. In the present study, we
      assessed retrospectively the efficacy and toxicity of the combination of
      carboplatin and oral cyclophosphamide in temozolomide-resistant patients.
      METHODS: We evaluated the medical records of 30 patients with malignant gliomas.
      After failure of temozolomide therapy, patients were treated with a combination
      of carboplatin and oral cyclophosphamide. Treatment consisted of intravenous
      carboplatin AUC 6 (based on the Calvert Formula) on day 1 and oral
      cyclophosphamide 75 mg/m2 daily on days 1 to 14, followed by 14 days of rest,
      with the treatment repeated every 4 weeks. RESULTS: All patients were evaluated
      for response and toxicity. The objective response rate was 30%, including 9
      partial responses. Median time to disease progression and median overall survival
      was 7 months and 8 months, respectively. Clinically responsive patients had
      statistically significant longer progression-free survival and overall survival
      than unresponsive patients. Hematological side effects were commonly observed
      toxicities, with neutropenia the most frequent. CONCLUSIONS: Our data suggest
      that carboplatin and oral cyclophosphamide therapy is a convenient regimen after
      failure of temozolomide therapy in patients with malignant gliomas because of its
      activity, feasibility and tolerability. Further prospective studies are needed in
      this setting.

PMID- 19112938
TI  - Diet and melanoma risk: effects of choice of hospital versus population controls.
AB  - AIMS AND BACKGROUND: Hospital-referred subjects are widely used as controls in
      studies on the relation between diet and cancer risk. However, concern has been
      raised about the potential for bias of such type of referents, and few studies
      seem to have examined their reliability in estimating dietary habits of the
      underlying general population. METHODS: In a northern Italian setting, the
      differences in dietary patterns between 41 individuals referred for non
      neoplastic lesions to hospital surgical outpatient units and age- and sex-matched
      subjects drawn from the general population were examined. The effects of such
      differences when carrying out a case-control study on a neoplastic disease,
      cutaneous melanoma, were also analyzed. Dietary intake was assessed using the
      EPIC food frequency questionnaire. RESULTS: Population controls showed higher
      intakes of energy, animal proteins and animal fats compared with sex- and age
      matched hospital controls, whereas intake of carbohydrates and fiber was
      comparable. An excess melanoma risk associated with intake of animal proteins and
      fats emerged when hospital controls were used as the referent group, whereas no
      such relation was detected when cases were compared to population controls.
      CONCLUSIONS: The results suggest that hospital-referred subjects may not reflect
      dietary habits of the underlying general population and may be unsuitable for
      case-control studies concerning the relation between diet and cancer risk.

PMID- 19112940
TI  - A retrospective analysis of the diameter of metastatic lymph nodes in apparently
      early stage endometrial cancer.
AB  - AIMS AND BACKGROUND: The objective of this retrospective study was to assess the
      diameter of metastatic lymph nodes in a population of women with apparently early
      stage endometrial cancer at laparotomy. METHODS AND STUDY DESIGN: Among 700 cases
      with endometrial cancer, 27 cases with disease clinically limited to the uterus
      in the laparotomy and found to have retroperitoneal node metastasis after
      pathologic examination were included in this study. Pathologic characteristics of
      the tumors, pelvic and para-aortic node counts and the largest diameter of each
      metastatic node were evaluated. RESULTS: The median number of nodes removed was
      38; median number of pelvic and para-aortic nodes was 29 and 8, respectively. A
      total of 85 metastatic nodes were identified. Mean diameter of the metastatic
      para-aortic and pelvic nodes was 6.8 mm and 9 mm, respectively. Nine patients had
      single metastatic nodes, and the diameters of the single metastatic para-aortic
      lymph node was 1 mm in one case, 2 mm in one case, 3 mm in one case and 4 mm in
      one, and 5 mm in two patients. Two cases had isolated para-aortic lymph node
      metastasis without pelvic lymph node metastasis. Diameters of the metastatic para
      aortic lymph nodes were 4 and 5 mm in one case and 4 mm in the other case.
      CONCLUSIONS: The diameters of metastatic nodes may be as small as 1 mm. By
      sampling or selective para-aortic and/or pelvic lymphadenectomy, some of the
      nodes might go undiagnosed, and such understaged cases cannot take adjuvant
      therapy (chemotherapy-radiotherapy). For correct staging of cases with
      endometrial cancer, complete systematic para-aortic and/or pelvic lymphadenectomy
      might be appropriate.

PMID- 19112937
TI  - Life tables for world-wide comparison of relative survival for cancer (CONCORD
      study).
AB  - BACKGROUND: The CONCORD study compares population-based relative survival from
      cancer using data from cancer registries in five continents. To estimate relative
      survival, general mortality life tables are required. Available statistics are
      incomplete, so various approaches are used to construct complete life tables.
      This article outlines how the life tables were constructed for CONCORD; it
      compares life expectancy at birth between 101 populations covered by cancer
      registries in 31 countries and compares the impact of two approaches to the
      deployment of life tables in relative survival analysis. METHODS: The CONCORD
      approach, using specific mathematical methods, produced complete (single-year-of
      age) life tables by sex, cancer registry area, calendar year (1990-1999) and race
      (only in the USA). In order to study the impact of different approaches, we
      compared relative survival in the USA using the US national life table, centered
      on the relevant census years, and the CONCORD approach. We estimated relative
      survival in each American participating cancer registry for patients diagnosed
      with breast (women), colorectal or prostate cancer during 1990-1994 and followed
      up to 1999. RESULTS: Average life expectancy at birth during 1990-1999 varied in
      CONCORD cancer registry areas from 64 to 78 years in males and from 71 to 84
      years in females. It increased during the 1990s more in men than in women. In the
      USA, it was lower in blacks than in whites. Relative survival in American
      populations was lower with the CONCORD approach, which incorporates trends and
      geographic variation in background mortality, than with the USA census life
      tables. CONCLUSIONS: International variation in background mortality by
      geographic area, calendar time, race, age and sex is wide. We suggest that in
      international comparisons of cancer relative survival, complete life tables that
      are specific for cancer registry area, calendar year and race should be used.

PMID- 19112941
TI  - Liposomal-encapsulated doxorubicin (Myocet; D-99) and vinorelbine in previously
      treated metastatic breast cancer patients: a feasibility study.
AB  - AIMS AND BACKGROUND: We conducted a feasibility study to determine the safety and
      efficacy of liposome-encapsulated doxorubicin (Myocet) and vinorelbine in
      previously treated metastatic breast cancer patients. PATIENTS AND METHODS:
      Liposome-encapsulated doxorubicin (30 mg/m2) plus vinorelbine (25 mg/m2) on days
      1 and 8, every 3 weeks were given until disease progression, sever toxicity or up
      to 9 cycles. All patients underwent tumor assessment before enrollment. Patients
      with a life expectancy longer than 3 months and measurable or assessable disease
      were eligible. RESULTS: Twenty-one patients were included. Median number of
      treatment cycles was 5 (range, 3-9). No complete response was obtained. Stable
      disease and/or partial response was obtained in 9 patients. Fifteen patients
      experienced grade 3-4 leukopenia. There was no significant decline in cardiac
      function. Non-hematological toxicity was tolerable (grade 1-2). CONCLUSIONS: The
      association of doxorubicin and vinorelbine has been shown to be feasible in
      previously treated advanced breast cancer patients. Its efficacy should be tested
      as first-line therapy in metastatic patients with cardiac co-morbidities.

PMID- 19112942
TI  - Disease presentation and outcome in very young patients with brain metastases
      from breast cancer.
AB  - AIMS AND BACKGROUND: Little information is available on disease presentation and
      treatment outcome in very young patients with brain metastases from breast
      cancer. Therefore, we evaluated our results in this group. METHODS: In our
      database, 7/74 breast cancer patients treated for brain metastases were < 40
      years old. All received whole-brain radiation therapy plus individual local or
      systemic measures. RESULTS: In patients with information available, tumors were
      poorly differentiated and metastatic to the axillary lymph nodes at primary
      diagnosis. All patients had extracranial metastases. Two died from their brain
      disease within 5 months. Five patients died from extracranial progression after 3
      84 months (2 long-term survivors beyond 2 years, characterized by single brain
      lesions and high performance status). CONCLUSIONS: Very young patients did not
      achieve a better outcome than intermediate age groups. Whole-brain radiation
      therapy plus surgery or radiosurgery provided durable CNS control in most of the
      patients. Improved systemic therapy appears to represent the key to a better
      outcome.

PMID- 19112943
TI  - The porta hepatis as a site of recurrence of mucinous appendiceal neoplasms
      treated by cytoreductive surgery and perioperative intraperitoneal chemotherapy.
AB  - BACKGROUND: A successful new treatment for a particular disease may change the
      natural history of that disease as patients go on to longer survival. The goal of
      this study was to investigate the porta hepatis as a site of recurrence of
      appendiceal mucinous neoplasms. METHODS: A prospective database on patients with
      peritoneal dissemination of mucinous appendiceal neoplasms has been maintained
      for 21 years. In patients with complete cytoreduction, disease
      progression/recurrence in and around the porta hepatis has been noted as a new
      manifestation of this disease. RESULTS: In 710 patients treated for mucinous
      appendiceal cancer with a complete cytoreduction, 140 developed recurrent
      disease. Seven patients (5%) had disease recurrence in and around the porta
      hepatis. Four of the seven had biliary obstruction and three had masses within
      the liver hilum not causing bile duct obstruction. Four of the seven patients
      were successfully palliated by surgical procedures within the liver and biliary
      tree. Two patients were successfully palliated using a biliary stent and one
      patient was not treated. CONCLUSIONS: Progression of mucinous neoplasms within
      the porta hepatis may be related to imperfect cytoreduction technique.
      Reoperative surgical treatment and biliary stents were beneficial in some of
      these patients.

PMID- 19112944
TI  - Insight into long-term histological, proliferative and apoptotic modifications in
      ileal orthotopic neobladder and conduit mucosa.
AB  - AIMS AND BACKGROUND: To assess the long-term histological, apoptotic and
      proliferating alterations of the intestinal mucosa of ileal conduits and
      orthotopic neobladders. METHODS: Fifty patients (46 males, 4 females), aged 52-78
      years, who underwent urinary diversion with either ileal orthotopic neobladder
      (group ON, 20 patients) or conduit (group IC, 30 patients) from 2001 to 2005,
      were included in this prospective study. Ileal samples were collected during
      surgery (controls) and by random mucosal biopsies 6, 12, 24, 36 and 48 months
      later. Histological (villi height, crypt depth, eosinophil cell count),
      proliferation (Ki67 immunochemistry), and apoptotic (Bcl-2 immunochemistry,
      TUNEL) parameters were assessed. RESULTS: During the 4-year follow-up, we
      recorded progressive villi area, height and crypt depth reduction, mucosa
      flattening, and inflammatory and eosinophilic infiltration. Villi height: crypt
      depth ratio showed a statistically significant difference (P < 0.05) between the
      two groups from the 6th month. Dysplasia, metaplasia, and neoplasia were not
      observed. Bcl-2 values showed a progressive increase until 24 months in group ON
      and 12 months in group IC, followed by a decline thereafter. Ki-67 values showed
      a progressive increase after 6 months in group ON and an increase until 24 months
      followed by a decline thereafter in group IC. TUNEL showed two peaks, at 24 and
      48 months. CONCLUSIONS: Histological adaptation was revealed in both groups, with
      statistically significant differences in favor of orthotopic substitution.
      Proliferative and apoptotic pathways are implicated as demonstrated by relevant
      modifications of Bcl-2, Ki-67 and TUNEL, in accord with the histological
      adaptation.

PMID- 19112945
TI  - Weekly concomitant boost in adjuvant radiotherapy for patients with early breast
      cancer: preliminary results on feasibility.
AB  - AIMS AND BACKGROUND: Recent advances in the management of patients with breast
      cancer are focused toward the reduction of overall treatment time of radiotherapy
      by delivering a dose biologically equivalent to a standard schedule. The aim of
      the present study was to evaluate the feasibility and preliminary toxicity of a
      moderately hypofractionated whole breast irradiation schedule with the addition
      of a concomitant boost delivered to the tumor bed once-a-week in patients with
      early breast cancer submitted to conservative surgery. MATERIALS: We selected
      patients with pT1c and pT2 N0/N+ M0 carcinoma of the breast with negative
      surgical margins. The basic course consisted of 4600 cGy prescribed to the ICRU
      50 reference point dose and delivered in 20 fractions, 4 times a week for 5
      weeks. Once a week, immediately after whole breast irradiation, a concomitant
      photon boost of 120 cGy was delivered to the lumpectomy area. Overall, according
      to the linear-quadratic model, the schedule provides a biologically equivalent
      dose of 87 Gy for breast tumor (assuming alpha/beta = 4 Gy), of 66 Gy for acute
      responding normal tissues (assuming alpha/beta = 10 Gy), and 99 Gy for late
      responding normal tissues (assuming alpha/beta = 3 Gy). Biologically, the
      schedule compares favorably with the 6-week conventional regimen consisting of 50
      Gy, 2 Gy/fraction, followed by a 10 Gy boost (BED(tumor), 90 Gy; BED(acute
      effects), 72 Gy, and BED(late effects), 100 Gy). RESULTS: From November 2004 to
      April 2007, we tested this radiotherapy schedule in 176 patients. All enrolled
      patients had achieved a minimum follow-up of 6 months and were considered in
      detail for the evaluation of feasibility. Three clinical examinations were
      performed by a group of independent physicians at treatment end, after 1 month
      and after 6 months. According to the RTOG/EORTC Toxicity Criteria, of the 176
      assessable patients at the end of radiotherapy, 58% showed grade 0-1 skin
      toxicity, 30% grade 2 and 12% grade 3. At one month of follow-up, grade 0
      toxicity was observed in 47% of cases, grade 1 in 46% and grade 2 in 7%. At 6
      months, late (skin and subcutaneous tissue) toxicity was assessed with the
      following scores: grade 0 in 68%, grade 1 in 26% and grade 2 in 6% of the
      patients. At 6 months, cosmesis was excellent, good and fair in 71%, 24% and 5%
      of patients, respectively. CONCLUSIONS: The explored adjuvant schedule planned to
      intensify the radiotherapy course for patients with early breast cancer by adding
      a weekly concomitant boost appears to be feasible and provides low local toxicity
      and excellent to good short-term cosmetic results.

PMID- 19112946
TI  - Effect of treatment on mononuclear cell migration in cervical cancer patients.
AB  - AIMS AND BACKGROUND: Our aim was to evaluate the effect of treatment on the in
      vitro migration of circulating mononuclear cells in cervical cancer patients at
      different stages. METHODS: We prospectively investigated 24 patients with
      cervical neoplasia, without prior treatment, submitted to surgery or chemotherapy
      as therapeutic conduct. Controls were healthy volunteer women (n = 23).
      Mononuclear cells were isolated from peripheral venous blood before and after
      treatment, and their migration capacity was evaluated in a microchemotaxis
      chamber assay towards the chemotactic stimuli fMLP, MCP-1 and RANTES, compared to
      basal migration. Serum levels of nitric oxide metabolites were assayed by the
      Griess reaction. RESULTS: Increased mononuclear cell migration in response to the
      chemotactic stimuli, compared to basal migration, was observed in controls and
      patients, without differences between them. After treatment (n = 14), mononuclear
      cell migration in response to MCP-1 and RANTES was increased compared to pre
      treatment. Serum levels of nitric oxide metabolites were more elevated in
      patients (n = 19) than in controls (n = 17), but decreased after treatment (n =
      15). CONCLUSIONS: The results suggest that the production of soluble circulating
      factors by tumor cells could interfere with the functional activity of blood
      mononuclear cells.

PMID- 19112947
TI  - P16 expression in odontogenic tumors.
AB  - AIMS AND BACKGROUND: The aim of the study was to examine the immunohistochemical
      expression of a cell-cycle-related factor (p16) in order to elucidate its role in
      the growth and diffusion of odontogenic tumors. STUDY DESIGN: Thirty-six
      odontogenic tumors were divided into two groups according to their clinical
      behavior: group A and group B composed of tumors at low and high risk of
      recurrences, respectively. The ANOVA test was used to detect differences between
      the two groups. RESULTS: p16 was expressed in both groups, but with different
      localization. A statistically significant difference was found in p16 expression
      of peripheral cells, with an increase in the expression in group B compared to
      group A (P < 0.05). In addition, there was no significant difference in p16
      positive expression of the central cells of odontogenic tumors, which was high in
      both groups. CONCLUSIONS: The present data show a correlation between p16
      expression and the biological behavior of odontogenic tumors.

PMID- 19112948
TI  - A guide of the questionnaires used in the measurement of health-related quality
      of life in head and neck oncology.
AB  - AIMS AND BACKGROUND: There is a plethora of instruments which measure health
      related quality of life (HRQOL), although only a fraction of these have been used
      in surgical studies and palliative care. Clinicians involved in the management of
      head and neck pathology face the difficult task of selecting the instrument most
      suited to the aspect of the patients' perspective that they want to measure. The
      aim of this article is to guide head and neck trainees in deciding on the use of
      the appropriate instrument for evaluation of the patient's perspective. METHODS
      AND STUDY DESIGN: The two authors independently searched and scrutinized the
      literature. The ISI search engine with cross-reference using PubMed and Ovid was
      searched with the terms "quality of life", "questionnaire" and specific specialty
      terms. Studies written in the English language were selected and the abstracts
      searched for evidence of patient self-completed questionnaires and HRQOL outcome.
      RESULTS: There are five broad category headings into which quality of life
      studies in head and neck oncology can be divided. These include: patient
      performance questionnaires, generic quality of life questionnaires, generic
      cancer questionnaires, head and neck cancer questionnaires, and head and neck
      functional questionnaires. CONCLUSIONS: Patient perspective can be assessed using
      a number of instruments, including open interview, semi-structured interview, and
      the simple questionnaire. The choice of instrument depends somewhat on personal
      preference, the outcomes being measured, and available resources.

PMID- 19112949
TI  - Management of mucinous urachal neoplasm presenting as pseudomyxoma peritonei.
AB  - BACKGROUND: Mucinous neoplasms of the urachus are rare malignancies so that the
      physicians' index of suspicion for a timely and accurate diagnosis is low. Also,
      this disease may present with a wide variety of symptoms and signs. METHODS: Two
      patients with pseudomyxoma peritonei as the initial presentation of urachal
      mucinous adenocarcinoma were treated successfully. The medical literature
      regarding treatment options for this manifestation of the disease was searched.
      RESULTS: Two patients with large volume of pseudomyxoma peritonei originating in
      a mucinous urachal neoplasm were treated with cytoreductive surgery and
      perioperative intraperitoneal chemotherapy. Our first patient required two
      reoperations to palliate the accumulation of gross mucinous ascites. She died 11
      years after diagnosis with progression of mucinous adenocarcinoma resulting in
      starvation. The second patient had ostomy closure with second look surgery at one
      year after definitive treatment; four small tumor nodules were seen and easily
      resected. The patient is currently without evidence of disease and has a normal
      quality of life. Seven prior manuscripts that report a single case of
      pseudomyxoma peritonei were reviewed to explore the full range of treatment
      options and survival for this rare condition. CONCLUSION: Cytoreductive surgery
      combined with perioperative intraperitoneal chemotherapy may be a new treatment
      option for mucinous urachal neoplasms presenting with pseudomyxoma peritonei.
      Other management strategies such as systemic chemotherapy seemed to hold little
      promise for this group of patients.

PMID- 19112950
TI  - A case of interstitial pneumonitis associated with Guillain-Barre syndrome during
      administration of adjuvant trastuzumab.
AB  - Optimal treatment for HER2/neu-positive, node-positive early breast cancer should
      include the monoclonal antibody trastuzumab. This relatively new agent has shown
      very limited pulmonary toxicity. Our report describes a case of life-threatening
      interstitial pneumonitis associated with Guillain-Barre syndrome that occurred
      during the administration of adjuvant trastuzumab. The severity of the clinical
      presentation and the limited number of reports in the literature of acute
      trastuzumab-related lung injury make the description of this case of crucial
      interest.

PMID- 19112951
TI  - Paralytic ileus associated with capecitabine.
AB  - Paralytic ileus is a temporary arrest of intestinal peristalsis. We report on two
      patients with breast cancer who developed paralytic ileus following treatment
      with capecitabine. The pathophysiology of this disorder and its possible
      connection to capecitabine are described with the aim of promoting the early
      recognition of the clinical picture so that unnecessary surgery can be avoided.

PMID- 19112952
TI  - Disseminated intravascular coagulation during treatment with thalidomide. A case
      report.
AB  - The treatment with thalidomide is associated with an increased risk of
      thromboembolic events, in particular when it is combined with chemotherapy or
      dexamethasone. However, despite this well-documented prothrombotic effect, to our
      knowledge disseminated intravascular coagulation has never been reported in
      hematological or oncological patients treated with thalidomide. We report a case
      of disseminated intravascular coagulation in a patient treated with thalidomide
      and dexamethasone for advanced, heavily pretreated hormone-resistant prostate
      cancer in which a relationship with the treatment appears highly likely.

PMID- 19112953
TI  - Fatal HBV-related liver failure during lamivudine therapy in a patient with non
      Hodgkin's lymphoma.

PMID- 19112954
TI  - Radiotherapy for perianal Paget's disease: a case report.
AB  - BACKGROUND: Perianal Paget's disease was first described in 1893. Since then,
      fewer than 300 cases have been reported in the literature. It might be associated
      with an underlying malignancy. Most of the patients are treated with surgical
      excision, which is often mutilating and of variable efficacy. In the present
      report, we describe the case of an 80-year-old woman with perianal Paget's
      disease. She was treated at our institution with radiotherapy with curative
      intent. The pertinent literature is reviewed, and the controversies in diagnosis
      and management are discussed. CONCLUSIONS: Our single-case experience supports
      the opinion that radiotherapy is a viable treatment option with curative
      potential for patients with perianal Paget's disease. For the treatment of in
      situ disease, hypofractionated regimens to a total dose of 40-44 Gy and
      orthovoltage X-ray beams are recommended.

PMID- 19112955
TI  - Woringer-Kolopp disease coexpressing CD4 and CD8 treated with radiation therapy:
      a case report.
AB  - We present an extremely rare case of Woringer-Kolopp disease with CD4+/CD8+
      immunohistochemical features in a 27-year-old male patient, which involved the
      right gluteal region continuing down to the lower thigh. Although the lesions had
      been present for 15 years, the disease abruptly changed its indolent clinical
      behavior in the last 3 months and gained local aggressiveness without features of
      dissemination. The patient was successfully treated with 6 MeV electron-beam
      radiotherapy and the radiation portal was determined to be the gross lesion plus
      1-cm margins around the lesion. Radiation therapy was administered with a
      hypofractionated dose schedule of 2.8 Gy per fraction in 13 fractions, 5 days a
      week, to a total of 36.4 Gy. No radiation-induced toxicity was reported during
      therapy. The patient's follow-up was ordinary with no recurrence after a follow
      up period of 38 months and the cosmetic result was excellent.

PMID- 19112956
TI  - Lymph node metastases of Merkel cell carcinoma from unknown primary site: report
      of three cases.
AB  - Merkel cell carcinoma (MCC) is an uncommon aggressive neuroendocrine skin
      carcinoma. It usually affects sun-exposed skin of white elderly people. MCC is
      characterized by a high incidence of early locoregional relapse and distant
      metastases. Because of its rarity and the resulting lack of prospective
      randomized trials, data regarding the optimal treatment of MCC are limited.
      Despite aggressive multimodality treatment, the prognosis of patients bearing MCC
      is often poor. We report three cases of lymph node metastases of MCC with unknown
      primary sites. Two patients died 17 and 28 months after diagnosis due to brain
      and pancreatic metastases, respectively, without evidence of cutaneous disease.
      The third patient is alive and free of tumor at 16 months from the diagnosis.
      After an accurate diagnosis of lymph node metastases from MCC, the absence of a
      primary tumor at complete initial evaluation and during adequate follow-up can
      confirm this particular clinical scenario. The prognosis seems to be analogous to
      that of cases with similar disease stage (lymph node involvement) but a known
      primary site.

PMID- 19112957
TI  - A rare cause of mastalgia: Dercum's disease (adiposis dolorosa).
AB  - Among the symptoms reported by patients undergoing breast imaging, pain is one of
      the most common. Mastalgia is generally classified as cyclic, noncyclic, or
      extramammary. A rare cause of breast pain is Dercum's disease, or adiposis
      dolorosa, a condition characterized by multiple, often painful subcutaneous
      lipomas. Painful breast lipomas have not been described in the literature so far.
      The diagnosis is made by clinical means supported by diagnostic imaging. We
      report the case of a 58-year-old postmenopausal woman affected by Dercum's
      disease in the breast. Ultrasound examination showed multiple oval, well-defined,
      hyperechoic lesions suggestive of breast lipomas. No significant features were
      detected by mammography.

PMID- 19112958
TI  - Diabetes insipidus caused by pituitary gland metastasis accompanied by iris
      metastasis of small cell lung cancer: case presentation and review of the
      literature.
AB  - Metastasis to the pituitary gland and iris is rarely seen in cancer patients.
      Breast cancer and lung cancer are the most common tumors that metastasize to
      these sites. Most lung cancer patients have non-small cell lung cancer and
      metastasis of small cell lung cancer to the pituitary gland and iris have been
      very rarely reported in the literature. Here we present a case of iris metastasis
      and pituitary gland metastasis which caused diabetes insipidus in a patient with
      small cell lung cancer.

PMID- 19112959
TI  - Prostate adenocarcinoma presenting with supraclavicular node enlargement: report
      of a case.
AB  - This report describes a case of prostate adenocarcinoma presenting with
      supraclavicular adenopathy and deep venous thrombosis in the ipsilateral arm.
      Biopsy revealed the enlarged node to be an undifferentiated adenocarcinoma of
      unknown origin, while CT scan evidenced widespread adenopathies. Because of the
      increase in serum PSA, the immunohistochemical staining of the biopsy specimen
      was reviewed and strong positivity for PSA suggested a prostatic origin. We
      emphasize the importance of PSA immunohistochemistry and serum PSA level
      monitoring in men presenting with carcinoma of undetermined origin and
      generalized lymphadenopathies.

PMID- 19112961
TI  - Irreversible cardiotoxicity after adjuvant treatment with trastuzumab in a case
      of breast cancer.

PMID- 19112960
TI  - Long-term survival after salvage surgery for invasive thymoma with intracardiac
      extension.
AB  - We report a case of successful salvage surgery for invasive thymoma initially
      judged to be unresectable that did not respond to sequential chemoradiotherapy.
      The patient underwent en bloc resection of the tumor, superior vena cava, upper
      portion of the right atrium (RA) and intracardiac neoplastic thrombus with the
      aid of a cardiopulmonary bypass without cardiac arrest. The patient is disease
      free 8.5 years after radical thymectomy and subsequent resection of 2 second
      primary lung adenocarcinomas.

PMID- 19112962
TI  - [Cilengitide: a new weapon against glioblastoma?].

PMID- 19112963
TI  - [Role of pemetrexed in the treatment of advanced non-small-cell lung cancer: news
      from ASCO, 2008].

PMID- 19112964
TI  - [ASCO 2008. Bevacizumab in advanced renal carcinoma].

PMID- 19112965
TI  - [Fatigue and its causes--who governs the connection?].

PMID- 19112966
TI  - [Resource centers for better diabetic care?].

PMID- 19112967
TI  - [No big reforms to be expected in American health care].

PMID- 19112968
TI  - [No scientific support for hypothermia therapy in severe craniocerebral injury.
      The treatment can even be dangerous].

PMID- 19112969
TI  - [Hospitals in Stockholm should concentrate more on health promotion. A
      questionnaire shows a lot of activities but goals and guidelines are missing].

PMID- 19112970
TI  - [If you are young you get it, but if you are old you are left out. The
      significance of age for choice of treatment and priorities in cancer care].

PMID- 19112971
TI  - [Now we can "read" the brain].

PMID- 19112972
TI  - [New methods for safe diagnosis and treatment in stroke].

PMID- 19112973
TI  - [Movement of water molecules and blood flow show the details of brain].

PMID- 19112974
TI  - [Images of the working brain].

PMID- 19112975
TI  - [MRS yields in vivo images of brain tissues].

PMID- 19112976
TI  - [Home care shortages threaten patient safety].

PMID- 19112977
TI  - [Can quality registry evaluate the quality of care?].

PMID- 19112978
TI  - [Bell palsy: Exclude neuroborreliosis prior to cortisone administration].

PMID- 19112979
TI  - [Continuous analysis of the proposal for revised priority guidelines is
      necessary].

PMID- 19112981
TI  - [No respect for different opinions].

PMID- 19112980
TI  - [Carbohydrate-restricted diet in diabetes and obesity is a physiological and
      evidence-based method].

PMID- 19112982
TI  - [Probiotics: keep research results and marketing arguments apart].

PMID- 19112983
TI  - [The Medical Products Agency's view on treatment of increased serum lipids].

PMID- 19112984
TI  - [The first Swedish female police officer was a nurse].

PMID- 19112985
TI  - [Testimony in a dark room--in Sweden as well ].

PMID- 19112986
TI  - [Image of the month. Autosomal dominant polycystic kidney].

PMID- 19112987
TI  - [Prophylaxis of infective endocarditis: improved dental care and oral health
      rather than systematic antibiotic prophylaxis?].
AB  - Prophylaxis for infective endocarditis has been recommended on the basis of the
      supposed pathophysiology of the disease, although no randomised clinical trial
      has confirmed its efficacy. Bacteraemia resulting from daily activities is much
      more likely to cause infective endocarditis than bacteraemia associated with
      invasive medical procedures. As a result, recommendations for antibiotic
      prophylaxis tend now to be severely restricted.

PMID- 19112988
TI  - [How I treat...recurrent labial herpes].
AB  - Recurrent oro-labial herpes is predominantly caused by the herpes simplex virus
      type 1. Following the primary infection, the virus remains in a latent stage in
      the trigeminal ganglion. After episodic reactivations, it is transported via the
      V1 or V2 axons to the lower or upper lip. Although no causal treatment exists, a
      series of therapeutic options are currently available. It now appears that
      recurrent oro-labial herpes can be treated with shorter treatment schedules with
      the currently available antiviral drugs. In these instances, similar clinical
      efficacy was obtained with increased compliance of the patient, and reduction in
      both the economical impact and the amount of drug intake. Newer treatment
      strategies are emerging including non medicated hydrocolloid dressings and
      combinations of a systemic antiviral drug with a topical corticosteroid.

PMID- 19112989
TI  - [Pleural effusion revealing Horton's disease].
AB  - Pulmonary involvement is rare in Horton's disease. Only few cases have been
      reported presenting as interstitial infiltration, pulmonary artery vasculitis,
      pulmonary nodules and granulome formation. Pleural effusion was rarely reported.
      A 65-year-old male patient presented with a right pleural effusion. Horton's
      disease was evoked in the presence of cephalgias, an ocular involvement and
      general signs. Temporal artery biopsy showed giant cell arteritis. After negative
      etiologic work up, pleural effusion was attributed to Horton's disease. Outcome
      was favourable with systemic corticosteroid therapy. Pleural involvment in
      Horton's disease is rare and characterized the absence of specific biological and
      histological findings. However, pleural effusion may be a presenting
      manifestation of Horton's disease.

PMID- 19112990
TI  - [Benefit-risk ratio of coronary drug-eluting stents: 2nd part: evaluation in the
      diabetic population].
AB  - The diabetic patient is at high risk of coronary heart disease. He/she can
      benefit of revascularisation procedures, even if he/she is exposed to a higher
      incidence of complications after a coronary artery bypass graft or a percutaneous
      transluminal coronary angioplasty. The use of drug-eluting stents--paclitaxel
      (PES) or sirolimus (SES)--dramatically reduces the risk of restenosis as compared
      to bare-metal stents; nevertheless, the rate of restenosis remains almost double
      in diabetic patients compared to that observed in non-diabetic subjects. However,
      the risk of (very) late thrombosis is higher with drug-eluting stents than with
      bare-metal stents, in the diabetic population as in the non-diabetic population.
      Altogether, among diabetic patients, the incidence of major cardiovascular events
      is significantly reduced with drug-eluting stents. This global clinical benefit
      essentially results from a diminution of revascularisation procedures rather than
      from a reduction of myocardial infarcts or cardiovascular deaths. Comparison
      between SES and PES gives discordant results. Indeed, while the loss of intra
      stent lumen is more important with PES than with SES, PES are associated with a
      lower rate of major cardiovascular events than SES. Efficacious antiplatelet
      therapy in the long run is mandatory in all diabetic patients treated with drug
      eluting stents.

PMID- 19112991
TI  - [Secondary amenorrhea and cerebral ventriculomegaly].
AB  - Cerebral ventriculomegaly and hydrocephalus are not frequently associated with
      endocrine disorders of the gonadotropic axis. The mechanism of this association
      is not clarified. The most probable cause is however a partial hypothalamic
      dysfunction. The examination of the few reported cases is in favour of this
      explanation. We present the case of a young woman with a cerebral
      ventriculomegaly and suffering from secondary amenorrhea. Shunt was not necessary
      from the neurological point of view, the problem of secondary amenorrhea and
      anovulatory infertility was solved by clomiphen citrate therapy.

PMID- 19112992
TI  - [Aortic pseudo-aneurysm after coarctation repair].
AB  - Aortic pseudo-aneurysm is a well-known late complication after surgical repair of
      aortic coarctation. We report two cases of pseudo-aneurysm of the aortic isthmus
      evidenced after previous surgical repair of congenital aortic coarctation. These
      clinical observations give us the opportunity to underline the importance of a
      specific lifelong medical follow-up for patients who have undergone such surgery.

PMID- 19112993
TI  - [Transdermal buprenorphine: a current overview of pharmacological and clinical
      data].
AB  - Our understanding of the pathophysiologic mechanisms of chronic pain progresses;
      the complexity of the problem justifies our need for new molecules and new ways
      of administration that will help to further optimise and better individualize our
      pharmacologic therapies. Whereas acute pain can be considered an alarm signal,
      chronic pain constitutes, per se, a syndrome that requires a meticulous selection
      of the analgesic drug(s). Since pain is permanent, the continuous administration
      of the analgesic is recommended rather than an on demand administration.
      Transdermic modes of administration are of value for the treatment of chronic
      pain because they allow a progressive delivery of the active compound together
      with the maintenance of stable plasma levels of the drug. Buprenorphine is a semi
      synthetic opioid that is available in the sublingual, injectable, or transdermic
      forms. The matrix patch of buprenorphine represents a major asset for the
      treatment of chronic pain, whether it be cancerous in origin, or not. Its
      efficacy and safety have been clearly demonstrated in randomised double blind
      trials as well as in post-marketing surveillance observations. Buprenorphine,
      administered as a transdermal therapeutic system, induces a dose-related pain
      relief, whatever the nature of the pain and the age of the patient. Buprenorphine
      also exerts an analgesic action on neuropathic pain. It differs from other
      opioids by its affinity as a partial agonist on mu and kappa receptors, and as a
      complete agonist of ORL-1 receptors. Therefore, transdermal buprenorphine will be
      useful to all physicians having to control severe pain by powerful opioids.

PMID- 19112994
TI  - [Pulmonary rehabilitation in chronic obstructive pulmonary disease].
AB  - The current treatment of chronic obstructive pulmonary disease (COPD) patients
      must comprise, in addition to an optimal pharmacological treatment, a pulmonary
      rehabilitation, if possible multidisciplinary, and a program of post
      rehabilitation in order to maintain the outcomes. Today pulmonary rehabilitation
      has proved to be effective in improving dyspnoea, exercise capacity and quality
      of life in COPD patients, and reducing the use of health services and thus the
      cost. In this article we want to present pulmonary rehabilitation, its
      indications and results, and the way by which it is held in the CHU of Liege.

PMID- 19112995
TI  - [The agony of rubbish to clinicians].
AB  - The clinician is at the crossroad between scientific information and some rubbish
      presentations of low level communication. In this background, searching for
      objectivity is mandatory in clinical trials. We summarize the main aspects of
      assessment on nominal scale, ordinal scale, interval scale as well as on
      structured and non structured scales.

PMID- 19112996
TI  - [Biphasic insulin aspart (NovoMix 50)].
AB  - Biphasic insulin aspart NovoMix 50 is a new premixed insulin preparation that
      contents 50% of ultra-short acting insulin analogue aspart and 50% of
      protaminated insulin aspart. As compared to NovoMix 30, NovoMix 50 results in a
      better control of postprandial hyperglycaemia thanks to a greater proportion of
      the ultra-short acting insulin analogue. Another preparation called NovoMix 70
      extends the panel of NovoNordisk, and will be soon commercialised in Belgium.
      These premixed insulin preparations can be used in one (rather rarely), two (most
      classically) or three (more and more frequently, i.e. before each of the three
      main meals) subcutaneous injections per day. They are used in the management of
      type 2 diabetes, eventually in association with metformin. These insulin
      preparations are available in Penfill cartridges for NovoPen. The launch of
      premixed insulin preparations, containing different proportions of short-acting
      and intermediate insulin formulations, offers a greater flexibility to medical
      doctors and facilitates the selection, according to the moment of the day, of the
      insulin mixtures that allow the best control of prandial and basal glycaemia,
      while limiting the risk of hypoglycaemia.

PMID- 19112997
TI  - [Drug selection guided by known and newly diagnosed comorbidities in a multi-risk
      patient].
AB  - The obese patient with osteoarthritis, arterial hypertension, type 2 diabetes,
      hyperuricaemia, mixed dyslipidaemia and moderate renal insufficiency is commonly
      seen in clinical practice. Besides life-style changes, the optimal management of
      such patient requires the use of a polymedication therapy whose choice should
      take into account not only possible pharmacological synergistic effects to
      warrant the best protection, but also contra-indications due to the presence of
      comorbidities or the risk of drug interferences.

PMID- 19112998
TI  - "Normal" adult development and aging can also be stressful. Considering the case
      of retirement.

PMID- 19112999
TI  - Prevalence and treatment of neuropsychiatric symptoms in advanced dementia.
AB  - Neuropsychiatric symptoms (NPS) are common in dementia, although little is known
      about their prevalence and treatment near the end of life. This study used a
      retrospective review of the medical records of 123 hospice-eligible nursing home
      residents with advanced dementia to investigate the prevalence of NPS and NPS
      targeted pharmacological and non-pharmacological treatments. The most prevalent
      NPS were agitation or aggression (50.4%), depression (45.5%), and
      withdrawal/lethargy (43.1%). Of the 105 (85.4%) residents who exhibited one or
      more NPS, 90.5% were receiving at least one NPS-targeted treatment, yet 41.9%
      received no documented nonpharmacological NPS-targeted care. The majority of
      documented nonpharmacological care focused on safety and explanations or
      instructions given to residents. Given the high prevalence of comorbidities,
      associated risks for medication interactions or serious side effects, and
      potential low-risk benefits of psychobehavioral care, these findings raise
      concerns about how to best increase the provision and documentation of
      nonpharmacological care in advanced dementia.

PMID- 19113001
TI  - Physical and psychosocial correlates of fear of falling: among older adults in
      assisted living facilities.
AB  - Fear of falling is the most common reported fear among older adults.
      Nevertheless, little is known about whom among this population develops fear of
      falling and why. This study aims to identify physical and psychosocial correlates
      of fear of falling among older adults in assisted living facilities. Data were
      collected from interviews with 208 residents using measures of fear of falling,
      physical and social functioning, depression, and state and trait anxiety. Results
      revealed that 48.6% of the participants had moderate to severe concern about
      falling. Stepwise multiple linear regression analysis revealed that use of a
      walking device, depression, balance impairment, trait anxiety, female gender, and
      a previous history of a fall or falls were independent factors associated with
      fear of falling. It is suggested that improving physical fitness and balance
      control and increasing one's self-efficacy and sense of control over the
      environment can decrease these sources of fear among older adults.

PMID- 19113000
TI  - Evaluation of comfort in bedridden older adults using an air-cell mattress with
      an automated turning function: measurement of parasympathetic activity during
      night sleep.
AB  - This study objectively evaluated the degree of comfort in bedridden older adults
      using an air-cell mattress with an automated turning mechanism. The sample
      included 10 bedridden women with verbal communication difficulties. The high
      frequency (HF) components of heart rate variability, which reflect
      parasympathetic nervous activity, were compared for the manual and automated
      turning periods. No significant differences in the HF component were observed in
      5 of the participants. Significant increases in the HF component associated with
      automated turning were observed in 3 participants; however, the two participants
      with the lowest body mass index values exhibited a significant reduction in the
      HF component during the automated turning period. The results revealed that
      comfort might not be disturbed during the automated turning period.

PMID- 19113002
TI  - Family satisfaction with care of a dying loved one in nursing homes: what makes
      the difference?
AB  - As part of a larger study examining end-of-life care in nursing homes,
      qualitative focus groups were conducted with bereaved family members to explicate
      those factors contributing to satisfaction and dissatisfaction with end-of-life
      care in the nursing home setting. Content analysis of focus group data revealed
      two overarching themes that influenced family members' satisfaction with care.
      These included: (a) ability of staff to recognize signs of imminent dying, and
      (b) communication and information sharing about the resident's status and plan of
      care. Family members dissatisfied with their relative's end-of-life care
      expressed feelings of guilt, anger, and frustration, both while the resident was
      alive and in the bereavement period. The findings of this study have implications
      for clinicians committed to delivering quality end-of-life care to residents and
      their families and provides the basis for educational interventions and quality
      care improvement initiatives in the long-term care setting.

PMID- 19113003
TI  - Promoting positive student clinical experiences with older adults through use of
      group reminiscence therapy.
AB  - Interest in psychiatric nursing as a practice area is associated with positive
      undergraduate clinical experiences that include staff acceptance, diverse
      learning opportunities, direct involvement with patients, and community
      placements. Essential student preparedness includes attitudes affirmative of
      patient recovery; assessment, communication, teaching, and medication
      administration and monitoring skills; and a toolkit of nursing interventions such
      as group facilitation and reminiscence therapy. In an innovative intervention,
      students in a geriatric psychiatric community setting developed and facilitated a
      support group with reminiscence-based activities to reduce social isolation.
      Patients increased social interactions, and students gained awareness of older
      adults' interests and self-identities, as well as confidence in providing care.

PMID- 19113004
TI  - Patients first, profession a close second.

PMID- 19113005
TI  - Global mission.

PMID- 19113006
TI  - A visual essay. Achieving aesthetic diastema closure and tooth length: a direct
      approach.

PMID- 19113007
TI  - A biometric approach to aesthetic crown lengthening: part II--interdental
      considerations.
AB  - Optimizing the aesthetic outcome for patients requiring periodontal aesthetic
      restorative treatment has become a primary objective in contemporary dentistry.
      Techniques that simplify and enhance quality of treatment provide substantial
      benefits to patients and clinicians. This article describes new concepts
      associated with interdental changes due to alterations in tooth and contact area
      position, and addresses the need for treatment of the interdental papillae. An
      innovative approach to aesthetic interdental periodontal crown lengthening will
      be discussed.

PMID- 19113008
TI  - Improving denture aesthetics with clear, resin-based baseplates.

PMID- 19113009
TI  - Postoperative patient considerations following soft tissue laser treatment.

PMID- 19113010
TI  - Aesthetic porcelain laminate veneer restoration following orthodontic treatment:
      sequential technique.

PMID- 19113011
TI  - Guided bone regeneration using an allograft material: review and case
      presentations.
AB  - Post extraction sites may have residual ridge deformities with insufficient bone
      present for future implant placement. This presents a challenge to the clinician
      attempting to obtain optimum results. To predictably augment these areas and
      obtain aesthetically pleasing results, bone grafting may be required. Guided bone
      regeneration with an allograft material is a predictable means by which to solve
      this challenge. This article describes three case presentations utilizing on
      allograft material for bone regeneration prior to implant placement.

PMID- 19113012
TI  - Aesthetic rehabilitation of the maxillary central incisors: predictable
      laboratory sequence.

PMID- 19113013
TI  - The evolving e-practice: effective treatment planning using dental charting
      software.

PMID- 19113014
TI  - Full-mouth rehabilitation using a multidisciplinary approach: material and
      periodontal considerations.
AB  - The complete aesthetic rehabilitation of dentition can be a complicated task. A
      multidisciplinary approach is often necessary to achieve ideal results. Clinical
      crown lengthening surgery can develop an aesthetic soft tissue profile and
      sufficient tooth structure for preparation and restoration. In addition, the
      development of novel all-ceramic zirconia materials has resulted in the delivery
      of improved aesthetics, function, and longevity. This article discusses the use
      of zirconia crowns in multidisciplinary full-mouth rehabilitation and provides
      recommendations to enhance the performance of these restorations.

PMID- 19113015
TI  - Through the glass ceiling.

PMID- 19113016
TI  - New chair of NMC questions the point of revalidation.

PMID- 19113017
TI  - Dignity in action.
AB  - Innovative nurses are finding new ways--and reinvigorating established methods-
      to ensure dignity is fundamental to their practice. Meanwhile, the RCN continues
      to campaign to put dignity at the centre of patient care.

PMID- 19113018
TI  - Post-it pitfalls.

PMID- 19113019
TI  - Provision of sex and relationships education for young people.
AB  - This literature review explores the provision of sex and relationships education
      (SRE) for young people, identifies emergent themes and outlines a school health
      nurse-led, evidence-based practice intervention. This intervention is intended to
      enable nurses to provide a programme of SRE for parents to educate their
      children.

PMID- 19113020
TI  - An introduction to causes, detection and management of hypertension.
AB  - This article examines the incidence of hypertension, the importance of early
      detection and the nurse's role. Lifestyle modification measures and medication
      are discussed, incorporating national guidelines.

PMID- 19113021
TI  - Resuscitating patients who have a cardiac arrest in hospital.
AB  - This article examines current guidance, recommendations atnd research on optimal
      management of patients who experience a cardiac arrest in hospital. The role of
      nurses is also explored.

PMID- 19113022
TI  - Female catheterisation.

PMID- 19113023
TI  - A question of preparation.

PMID- 19113024
TI  - Learning the skills to save lives.

PMID- 19113025
TI  - Monitoring staff progression.

PMID- 19113027
TI  - [Porcine circovirus 2 (PCV2)--associations between sequence, function and
      virulence].
AB  - Presently, potential associations between PCV2 virulence and -sequence are
      discussed controversially. Practitioners are rattled, whether and to which extent
      spatio-temporal variations in PCV2 associated diseases (PCVD) on farms might be
      attributed to distinct PCV2 strains, differing in virulence, and if this factor
      should be taken into account regarding diagnosis and prophylaxis. The present
      paper provides a review on known and discussed functional elements of the PCV2
      genome and their significance in pathogenesis is discussed. Furthermore,
      variability between and within PCV2 strains and discrepancy between the common
      phylogenetic considerations of the total genome or the open reading frame 2 (ORF
      2) and single nucleotide variations are presented. Only incoherent associations
      between phylogeny and virulence determining sequences serve as an explanation for
      inconsistent results of different authors regarding sequence and virulence. The
      conclusion is that there are presently no molecular markers for PCV2 virulence.
      Thus, quantitative considerations still remain the major factor in diagnosis,
      prognosis, prophylaxis and control of PCVD.

PMID- 19113026
TI  - Concentrations of beta-carotene (Carofertin) and vitamin A in plasma of pigs
      after intramuscular injection of beta-carotene.
AB  - Limited information is available about the absorption and distribution of
      parenterally administered beta-carotene in pigs.Therefore plasma concentrations
      and pharmacokinetic parameters of beta-carotene, its influence on plasma vitamin
      A concentration as well as the safety and tolerability of an intramuscularly
      administered beta-carotene preparation (Carofertin) were analysed. Five gilts
      were injected with a single dose of 70 mg beta-carotene in an injectable aqueous
      solution. The mean pre-treatment plasma beta-carotene concentration was below 10
      microg/ml. After injection, plasma beta-carotene values increased rapidly and
      reached a peak of 13.8 +/- 5.4 microg/ml after 24 hours. For a duration of 72
      hours, plasma beta-carotene concentrations were significantly increased compared
      to baseline values (p < 0.05).The mean half-life of beta-carotene in plasma was
      7.2 +/- 1.4 hours.The single dose of 70 mg beta-carotene did not significantly
      affect plasma vitamin A concentrations. Tolerability and safety of the
      administered preparation were good. No side effects related to the medication
      were observed.

PMID- 19113028
TI  - Blockade of p-selectin reduces neutrophil infiltration into the murine testis
      after ischemia-reperfusion-injury.
AB  - Germ cell specific apoptosis after ischemia-reperfusion (I/R) induced testicular
      injury is dependent on neutrophil recruitment to the testis. Intravascular
      adhesion molecules like the P- and E- selectins play an important role in this
      recruitment.The purpose of this study was to inhibit neutrophil recruitment in
      I/R induced testicular injury by using a function-blocking monoclonal anti-mouse
      P-selectin antibody. Adult mice were subjected to a 2 h period of testicular
      torsion (ischemia) followed by detorsion (reperfusion).Ten minutes after the
      onset of reperfusion, mice received either 100 microg of a function-blocking
      monoclonal P-selectin antibody (FBMAB group) or isotype-matched control antibody
      (IMCA group). Separate groups of mice underwent sham-operation (SO group) or
      received 500 ng of TNFalpha (IF group) to induce inflammation. Mice were
      sacrificed 24 h after reperfusion and testiscular interstitial cells were
      isolated and analyzed for the presence of neutrophils by means of flow cytometry.
      The function-blocking monoclonal P-selectin antibody reduced neutrophil
      recruitment in I/R induced testicular injury significantly (FBMAB group as
      compared to the IMCA group 26 +/- 4 vs. 52 +/- 10% Gr-1 +CD11 b+ of total
      leucocytes; P < 0.001). Therefore, blocking P-selectin may be therapeutically
      beneficial to protect postischemic testis.

PMID- 19113029
TI  - [Detection of psittacid herpesvirus 1 in Amazon parrots with cloacal papilloma
      (internal papillomatosis of parrots, IPP) in an aviary of different psittacine
      species].
AB  - Amazon parrots (Amazona aestiva aestiva;Amazona ochrocephala, n=6) from an aviary
      with different psittacine species (n=100) were submitted to the Clinic for Pet
      Animals, Reptiles, Pet- and Wild birds with the clinical picture ofa cloacal
      prolaps. The cloacal mucosa showed papillomas, and internal papillomatosis of
      parrots (IPP) was suspected. Hepatomegaly was detected in the radiographs of the
      clinically diseased amazon parrots, indicating the involvement of the liver in
      the disease process. The cloacal area was enlarged and showed higher densities in
      the radiographic picture. One of the amazons had an increased level of bile acids
      in the plasma supporting the suspicion of the involvement of the liver.
      Macroscopical and histological investigation of amazons with cloacal prolaps
      revealed a papillomic adenoma of the cloacal mucosa accompanied by varying
      degrees of bile duct carcinomas in the liver and adenocarcinomas of the pancreas.
      Herpesvirus genome was detected by nested PCR in cloacal swabs, liver, and
      cloacal tissue samples. Sequencing of part of the herpesvirus DNA-polymerase gene
      indicated 95% homology of the detected herpesviruses with the Psittacid
      Herpesvirus (PsHV) 1. No cytopathic herpesvirus was recovered from cloacal swabs
      and liver samples after up to four passages in chicken embryofibroblast cultures.
      Cloacal and choanal swabs, which were taken from the remaining 47 healthy amazon
      parrots and 5 Green-winged Macaws (Ara chloroptera) of the aviary, were negative
      for herpesvirus in the nested PCR. Only birds with cloacal papillomas and the
      Green-winged Macaws were tested positive for herpesvirus DNA in the nested PCR.
      We may speculate that there is correlation between the infection with PsHV-1 and
      the development of cloacal adenomas, adenocarcinomas in the pancreas and
      carcinomas of the bile ducts. Our results indicate that there may be a higher
      susceptibility in certain amazon species, while other species may not get
      infected even if housed in close contact to infected birds. A therapy approach
      with the immunomodulator Imiquimod did not improve the clinical disease of the
      birds, although circulating interferon levels were detected in serum samples of
      treated birds. We may speculate that in the case of already developed tumors an
      Imiquimod therapy may not lead to tumor regression.

PMID- 19113030
TI  - Frequency of BLAD and CVM alleles in sires and elite heifers of Czech Holstein
      cattle.
AB  - In this paper, we analyse the occurrence of BLAD and CVM heterozygous animals in
      Holstein cattle in the Czech Republic in 1993-2005. The occurrence of BLAD
      heterozygous sires and heifers (BL) during the period 1993-1998 in Czech
      Holsteins was 13.9% and 10.7%. Radical measures have been taken to restore the
      population. Evidently, the measures have been efficient, in 2005 one BLAD
      heterozygous sire of 101 was found. Continuous testing is necessary, because in
      commercial herds, the eradication process is not short-term. The found occurrence
      ofCVM heterozygous sires (CV) decreased from 20% in 2001 to 8% (7 positive of 85)
      in 2005.This is still quite a high frequency. The occurrence in CV females of 20%
      remains higher. Therefore, the use of CV sires should be restricted thoroughly.
      Identification of the molecular basis for inherited diseases, should lead to
      control measures which would enable the quick recovery of the population.

PMID- 19113031
TI  - The Health in Pregnancy Grant is good news.

PMID- 19113032
TI  - The new Health in Pregnancy Grant.
AB  - From April 2009, pregnant women throughout the UK will be eligible for the Health
      in Pregnancy Grant. This is a one-off, non-means-tested payment of pounds 190 to
      support the general health and well-being of women in the later stages of
      pregnancy, for example through a healthy lifestyle and diet, and help with some
      of the costs before the birth. The grant is part of a Government strategy to
      reduce health inequalities and improve pregnancy outcomes. A midwife or doctor
      will be required to sign the claim form, and health professionals will therefore
      have an essential role in ensuring women receive the grant.

PMID- 19113033
TI  - Approaches for the unimmunised--one size does not fit all.
AB  - The majority of children receive a full course of childhood vaccinations, a
      proportion do not complete the course and some children receive no vaccinations
      at all. The reasons for this are diverse; various strategies are needed to
      maximise uptake. Recent research provides insights into how best to target our
      efforts.

PMID- 19113034
TI  - Exercise and children's bone health.
AB  - Physical activity in childhood has potential benefits for bone health and many
      other health outcomes. A number of studies have demonstrated that exercise can
      enhance bone gains in children and adolescents. Activities that impose high loads
      on bone seem most effective, and relatively brief bouts of such exercise are
      adequate. Exercise seems to be most effective during early puberty, and some
      benefit of childhood exercise seems to be retained longer term, whilst in adults
      exercise effects on bone seem to be reversed on cessation. Activity that produces
      sustained increases in heart rate and energy expenditure can help with weight
      control and cardiovascular fitness, which may reduce risk of future
      cardiovascular disease and type 2 diabetes. Unfortunately, many children and
      adolescents (particularly adolescent girls) do not meet the recommended 60
      minutes per day of exercise and it is unclear how many do adequate "bone-loading"
      exercise to optimise bone accrual. Increasing the amount of exercise, and
      incorporating "bone loading exercise" may thus be beneficial in children and
      adolescents.

PMID- 19113035
TI  - Setting the pace on health equality: the Pacesetters programme in Leicester.
AB  - A founding principle of the 60-year-old National Health Service in the United
      Kingdom (UK) was a commitment to equal access and treatment for all, regardless
      of social class, income or status. In keeping with this principle, the Department
      of Health has launched the Pacesetters programme to reduce inequalities and
      discrimination experienced by people in some of the UK's increasingly diverse
      communities when accessing health care. A key theme is to stimulate innovative
      local schemes involving patients and service users, health professionals and the
      local community in the design and delivery of services. The programme is being
      piloted by selected health Trusts in England. Two schemes are described in one
      Trust in Leicester. The first involves members of the Traveller and Gypsy
      communities in becoming health ambassadors, learning about the health services
      and sharing their knowledge with their communities. Health professionals learn
      alongside them about Traveller and Gypsy culture and approaches to health. In the
      second scheme, health professionals are working with the city's Lesbian, Gay and
      Bisexual Centre to understand how to make the health services more welcoming and
      appropriate for the lesbian, gay and bisexual community. The three-year pilot
      schemes will be externally evaluated and may be incorporated in mainstream
      services if successful.

PMID- 19113036
TI  - Managing depression in the postnatal period.
AB  - Mental health disorders following childbirth are common. The nature and treatment
      of mental disorders occurring in the perinatal period may differ from those
      occurring at other times but there are also false beliefs that postnatal
      depression differs in important ways from other depressions. Vulnerable women can
      be identified in the antenatal period, and intervention before delivery can
      prevent or lessen the severity of postnatal psychiatric problems. Various
      treatment options are available for professionals to discuss with mothers.

PMID- 19113037
TI  - Amalgamated School Nurses' Association: an independent modern voice for school
      nursing.

PMID- 19113038
TI  - 'Health for All' Alma-Ata Declaration--an elusive Holy Grail.

PMID- 19113039
TI  - Doctors' dress code.

PMID- 19113040
TI  - Gay community to test HIV prevention pill.

PMID- 19113041
TI  - Slow progress in doctor placement kickback probe.

PMID- 19113042
TI  - Runaway TB epidemic--can we catch up?

PMID- 19113043
TI  - ALP-Health Dept TB skirmish to bear fruit?

PMID- 19113044
TI  - Community health workers in South Africa: where in this maze do we find
      ourselves?

PMID- 19113045
TI  - Interpersonal violence prevention: prioritising interventions.

PMID- 19113046
TI  - Road traffic injury: prioritising interventions.

PMID- 19113047
TI  - The eye in antiquity.

PMID- 19113048
TI  - Alma-Ata Declaration on Primary Health Care: 30th anniversary.

PMID- 19113049
TI  - Reducing the burden of injury: an intersectoral preventive approach is needed.

PMID- 19113050
TI  - Rheumatoid arthritis functional disability in a public health care clinic.

PMID- 19113051
TI  - Reliability of HIV rapid tests is user dependent.

PMID- 19113052
TI  - Intestinal parasitic infections in adult patients in KwaZulu-Natal.

PMID- 19113053
TI  - Closed suction drainage versus closed simple drainage in the management of
      modified radical mastectomy wounds.
AB  - OBJECTIVE: To compare the outcomes of modified radical mastectomy wounds managed
      by closed wound drainage with suction and without suction. METHOD: A prospective
      randomised trial was conducted at the University College Hospital in Ibadan, and
      the University of Nigeria Teaching Hospital in Enugu. Fifty women who required
      modified radical mastectomy for breast cancer were randomised to have closed
      wound drainage with suction (26 patients) and closed wound drainage without
      suction (24 patients). RESULTS: There was no significant difference in the
      intraoperative and postoperative variables. Suction drainage drained less volume
      of fluid and stayed for a shorter time in the wound, but the differences were not
      significant. There was no difference in the length of hospital stay, time to
      stitch removal, and number of dressing changes. More haematomas and wound
      infections occurred in the simple drain group while more seromas occurred in the
      suction drain group, but these were not significant. The suction drain was more
      difficult to manage and the cost was 15 times higher than the simple drainage
      system. CONCLUSION: Closed simple drains are not inferior to suction drains in
      mastectomy wounds and, considering the cost saving and simplicity of
      postoperative care, they are preferable to suction drains.

PMID- 19113054
TI  - Fatal road traffic accidents in the Mthatha area of South Africa, 1993-2004.
AB  - BACKGROUND: Trauma is one of the leading causes of death in the Mthatha area,
      which is one of the least developed regions of South Africa. Road traffic
      accidents (RTAs) contribute substantially to the number of such deaths.
      OBJECTIVE: To estimate the number of fatal RTAs in the Mthatha area, and analyse
      age and sex of the deceased. METHODS: A review of autopsies performed in the
      Mthatha General Hospital mortuary was conducted. Data were analysed using the
      GENSTAT 9 package with a Poisson regression model. RESULTS: There were 2736
      deaths from RTAs over the 12-year period 1993-2004 in the Mthatha area. These
      casualties constituted an average annual rate of 57 deaths per 100 000
      population. The highest (69.4/100 000) was in 1998, and the lowest (40.2/100 000)
      in 2001. Males outnumbered females by 2.6:1 (95% confidence interval (CI) 2.13
      3.22), and the rate showed a decline of 0.97/100 000/year (95% CI 0.95-0.99) for
      the 1998-2001 period. The rate of decline was the same for males and females. The
      highest annual rate was 14.2 per 100 000 population in the age group 21-30 years,
      and the lowest, of 2.6 per 100 000 population, in the group above 70 years of
      age. The death rates were related to sex (p<0.001) and calendar year (p<0.049).
      There was no significant connection between year and sex, implying that the
      effect of year (time) was the same for men and women. These results are
      statistically significant despite the very high variability in the data
      (S2=5.53). CONCLUSION: RTA-related deaths in the Mthatha area are 3 times higher
      than the global average.

PMID- 19113055
TI  - Otosclerosis and TGF-beta 1 gene in black South Africans.
AB  - Limited literature is available on the epidemiology and genetics of otosclerosis
      in South African blacks, among whom it is extremely rare. We undertook this study
      because we had documented and surgically confirmed cases of clinical oval window
      otosclerosis in this population.

PMID- 19113056
TI  - Cryptococcus and lymphocytic meningitis in Botswana.
AB  - We retrospectively reviewed microbiological data from a tertiary care hospital in
      Botswana, and found that Cryptococcus neoformans was cultured from 15% (193/1307)
      of all cerebrospinal fluid (CSF) specimens submitted for analysis, making it the
      most common diagnosed cause of meningitis in this population. Moreover, almost
      70% of CSF samples with significant lymphocytosis did not yield a pathogen,
      suggesting that many causes of lymphocytic meningitis go undiagnosed.

PMID- 19113057
TI  - The quality of operative notes at a general surgery unit.
AB  - AIM: With the increasingly litigious nature of medical practice, accurate
      documentation is critical. This is particularly true for operative procedures,
      and medical councils have identified this and published guidelines to aid
      surgeons. However, these remain a frequently cited weakness in their defence in
      medico-legal cases. This study assessed the accuracy of operative notes in a
      general surgery unit in order to improve our practice. METHOD: An audit of 100
      consecutive operative notes was performed, and notes were assessed using the
      Royal College of Surgeons guidelines. The quality of note-taking of trainees was
      compared with that of consultant surgeons. A series of operation note pro formas
      was designed in response to the findings. RESULTS: Of the notes, 66% were
      completed by trainees. The vast majority of notes had no diagram to demonstrate
      the surgical findings or illustrate the actions. Specialist surgeons were more
      likely to describe the actions accurately, but less likely to describe wound
      closure methods or dressings used. They were also less likely to complete
      adequate postoperative orders. CONCLUSIONS: This study identifies key areas of
      weakness in our operative note-keeping. Pro formas should be introduced and made
      available for commonly performed procedures, and diagrams should be used wherever
      possible.

PMID- 19113058
TI  - Medicaid rate hike an enormous opportunity.

PMID- 19113059
TI  - Victory!

PMID- 19113060
TI  - Tort reform protected.

PMID- 19113061
TI  - A "clear" win.

PMID- 19113062
TI  - TMA takes on cancer.

PMID- 19113063
TI  - Keeping them home.

PMID- 19113064
TI  - Subnormal prealbumin levels and wound healing.

PMID- 19113065
TI  - Elective induction of labor: part 1.

PMID- 19113066
TI  - Descriptive epidemiology of non-Hodgkin's lymphoma in Oklahoma: 1997-2003.
AB  - OBJECTIVE: To describe the incidence of Non-Hodgkin's lymphoma in Oklahoma
      residents. METHODOLOGY: Case data were obtained from the Oklahoma Central Cancer
      Registry for Oklahomans diagnosed between 1997 and 2003. Age-adjusted incidence
      rates (AAIR) and standardized incidence ratios (SIR) were calculated for four
      racial and ethnic groups as well as four histological subtypes. RESULTS: 3,687
      cases were diagnosed between 1997 and 2003, which was an average age-adjusted
      incidence rate of 14.9 cases per 100,000 Oklahomans. A 23% increase occurred in
      the AAIR between 1997 and 2003. A non-significantly elevated SIR was found among
      American Indians (AI) when compared to Whites: 1.12 (0.78-1.18). African
      Americans had a significantly lower SIR when compared to Whites: 0.72 (0.44
      0.79). AI males were found to have increasing incidence throughout their
      lifetime, with the highest rate occurring in the oldest age group. This differs
      from the other racial/ethnic groups analyzed whose rates decreased in this age
      group. CONCLUSIONS: Further research is warranted to identify factors that may
      increase risk of development of NHL for American Indians in Oklahoma.

PMID- 19113067
TI  - Suicide among persons 65 years and older, Oklahoma, 2004.

PMID- 19113068
TI  - Broadcast yourself--the YouTube phenomenon.

PMID- 19113069
TI  - Kansas public health system improvements: structural implications for
      sustainability.

PMID- 19113070
TI  - Kansas Health Institute issue brief: employer-sponsored insurance in Kansas.

PMID- 19113072
TI  - Are ratings of dentofacial attractiveness influenced by dentofacial midline
      discrepancies?
AB  - AIMS: To assess the attractiveness of dentofacial midline discrepancies during
      smiling, and to determine if the ratings were influenced by the gender of the
      judges. METHODS: Twenty non-dental undergraduate students (10 males, mean age:
      33.5 years; 10 females, mean age: 31.2 years) and 20 orthodontists (10 males,
      mean age: 36.6 years; 10 females, mean age: 34.3 years) assessed frontal
      photographs of the same smiling adult female with coincident midlines, and images
      of the same person with the upper dental midline shifted 2 mm and 4 mm to the
      right and left of the facial midline. The judges scored the attractiveness of the
      smile using 5-point scale. RESULTS: Both the students and the orthodontists
      considered that the images were less attractive as the dentofacial midline
      discrepancy increased. More orthodontists than undergraduate students, and more
      female orthodontists than male orthodontists, considered a 4 mm discrepancy
      between the dental and facial midlines as unattractive. CONCLUSION: Dental to
      facial midline discrepancies reduce dentofacial attractiveness. Discrepancies of
      2 mm or more are likely to be noticed by both orthodontists and non-dental
      university students. Orthodontic treatment objectives should include correction
      of the dental midline discrepancies to within 2 mm of the facial midline.

PMID- 19113071
TI  - Accuracy and validity of space analysis and irregularity index measurements using
      digital models.
AB  - BACKGROUND: Digital copies of study models may avoid the storage and retrieval
      issues of plaster study models, but measurements made on digital models may not
      be as accurate as measurements made on traditional study models. AIM: To
      determine the reliability and validity of tooth size-arch length discrepancies
      (TALD), irregularity indices and arch lengths (four- and six-segment analyses)
      measured directly on study models with digital calipers with the same
      measurements measured on digital copies of the study models with proprietary
      software. METHODS: The irregularity indices and TALDs (four- and six-segments)
      were measured on 50 sets of pretreatment plaster models. The plaster models were
      measured using manual calipers with a digital readout. The models were then
      couriered to OrthoCAD and digital copies emailed to the authors. The digital
      models were measured with the proprietary software provided with the digital
      models. Repeat measurements of the TALDs and the irregularity indices were
      subjected to intraclass correlations (ICC) to assess the reliability. The least
      squares means of variation was used to assess validity and the impact of
      measuring arch length (four- and six-segments) on the digital models, and the
      implications on the TALDs. RESULTS: There were high correlations (ICC) ranging
      from 98.6-99.9 per cent for both the irregularity indices and the TALDs. The
      choice of manual over computer and four-segment over six-segment analysis had a
      significant effect when measuring lower arch lengths (p < 0.05), but they had no
      effect on the upper arch findings. CONCLUSIONS: Reliable measurements of the
      irregularity index and the TALD can be made on digital models. Computer
      measurements of TALDs on digital models were more consistent than manual
      measurements of TALDs on plaster models. Six-segment analyses of lower arch
      lengths on digital and plaster models gave more consistent findings than the four
      segment analyses.

PMID- 19113073
TI  - Comparison of methods used to correct a lingually tilted mandibular molar: 3-D
      analysis using the finite element method (FEM).
AB  - BACKGROUND: Methods used to upright lingually tilted mandibular molars frequently
      result in extrusion and unwanted rotations. AIM: To use the finite element method
      (FEM) to compare three springs designed to upright a lingually tilted mandibular
      first molar. METHODS: A 3-D computer model of a lingually tilted mandibular first
      molar was designed. The FEM was used to compare movement of the molar during
      uprighting with either a single horizontal helix, an open vertical loop, or a new
      spring with two vertical helices wound around and perpendicular to the long axis
      of the archwire. Each spring was assumed to be part of a continuous 0.016 x 0.022
      inch stainless steel archwire, and each spring was placed mesial to the buccal
      tube on the first molar. RESULTS: From the mesial perspective, all designs moved
      the crown of the lingually tilted molar buccally and the root apex lingually.
      From the occlusal perspective: the horizontal helix uprighted the molar with a
      disto-buccal rotation; the open vertical loop uprighted the molar with a mesio
      buccal rotation; and the new design uprighted the lingually tilted molar around a
      mesio-distal axis. CONCLUSION: Using FEM, the most suitable design was a double
      helix formed around and perpendicular to the long axis of the archwire and sited
      mesial to the tilted molar. It was the only spring to upright the lingually
      tilted molar without an unwanted rotation.

PMID- 19113074
TI  - Comparison of active self-ligating brackets and conventional pre-adjusted
      brackets.
AB  - BACKGROUND: Active self-ligating brackets may be more efficient than conventional
      pre-adjusted brackets. AIMS: To determine if self-ligating brackets are more
      efficient than conventional pre-adjusted brackets when used in a specialist
      practice setting. METHODS: Seven hundred and sixty two patients, consecutively
      treated with fixed appliances, were evaluated retrospectively. All patients were
      treated by one orthodontist in a private orthodontic practice. Three hundred and
      eighty three patients were treated using a conventional pre-adjusted bracket
      system and 379 patients were treated with active self-ligating brackets. The
      total treatment time, number of appointments, appointment intervals, number of
      bracket breakages and number of unscheduled emergency appointments were recorded.
      Pretreatment characteristics identified by the ICON were related to these
      variables. RESULTS: The average treatment duration was 15.7 months (Range: 4.1
      40.5 months; SD: 5.6 months). Comparable amounts of time were spent in
      rectangular and round archwires by both appliances. Overall, there was no
      statistically significant difference between the durations of treatment with
      active self-ligating brackets and conventional pre-adjusted brackets. The number
      of debonded brackets and other emergency visits was significantly higher in
      patients treated with active self-ligating brackets. The treatment
      characteristics associated with prolonged treatment were: extraction of teeth, a
      Class II molar relationship and the degree of maxillary crowding or spacing.
      CONCLUSIONS: Active self-ligating brackets appear to offer no measurable
      advantages in orthodontic treatment time, number of treatment visits and time
      spent in initial alignment over conventional pre-adjusted orthodontic brackets.

PMID- 19113075
TI  - The effects of bracket removal on enamel.
AB  - BACKGROUND: Enamel cracks, which may develop during debonding orthodontic
      brackets, may jeopardise the integrity of the enamel and detract from the
      appearance of the teeth. AIM: To compare the adhesive remnant scores (ARI), the
      number, lengths and directions of enamel cracks before bonding and after
      debonding metal orthodontic brackets with three different methods. METHODS: Metal
      brackets were bonded with a self-curing orthodontic adhesive to the buccal
      surfaces of 75 recently extracted upper and lower premolars. The teeth were
      randomly divided into three groups, and the brackets removed either with a side
      cutter, a single-blade bracket remover or a two-blade bracket remover. The
      number, directions and lengths of the enamel cracks before bonding and after
      debonding were compared. The number of 'pronounced' cracks (i.e. cracks that
      could be identified with the naked eye) and the ARI scores in each group were
      also compared. RESULTS: After debonding, the number of enamel cracks and
      pronounced cracks, and the lengths of the enamel cracks increased in all groups
      (p < 0.001). There were no statistically significant differences between the
      groups. The ARI scores and the direction of propagation of the enamel cracks were
      not influenced by the debonding method used (p = 0.73). CONCLUSIONS: Concerns
      about the enamel damage caused by the three methods of debonding justify caution.
      Despite widespread use of these methods, it would be sensible to search for
      methods that result in less enamel damage.

PMID- 19113076
TI  - Mechanomyogram and electromyogram analyses during isometric contraction in human
      masseter muscle.
AB  - AIMS: To investigate the relationship between mechanomyogram (MMG),
      electromyogram (EMG) and bite force during isometric contraction of the human
      masseter muscle. METHODS: Data were obtained from 16 healthy Japanese males (Mean
      age: 25.6 +/- 2.3 years). The measuring device for MMG consisted of an amorphous
      sensor and a small magnet. The bite force, MMG and EMG signals were recorded
      simultaneously during isometric contraction of the masseter muscle. The subjects
      were instructed to perform 0, 5, 10, 20, 30, 40, 50, and 60% maximal voluntary
      contractions (MVC) for 20 seconds. The average rectified value (ARV) for MMG and
      EMG were calculated from 1 to 5 second samples. The median frequency of the power
      spectrum (MFPS) for MMG and EMG were determined with the use of a fast Fourier
      transformation algorithm. RESULTS: The mean ARV for MMG increased up to 20% MVC
      and then gradually decreased at the higher force levels. The mean ARV for EMG
      increased with bite force in a monotonic fashion. The mean MFPS for MMG clearly
      increased up to 10% MVC and then gradually increased. On the other hand, the mean
      MFPS for EMG clearly increased up to 10% MVC, but then gradually decreased with
      bite force. CONCLUSION: These findings suggest that the MMG analysis combined
      with the EMG may be a more useful method for evaluating the status of the
      masseter muscle.

PMID- 19113077
TI  - The effects of systemic stress on orthodontic tooth movement.
AB  - OBJECTIVES: To determine if systemic stress affects the biological reactions
      occurring during orthodontic tooth movement. METHODS: Four groups of male 10 week
      old Wistar rats were used. Group A animals (N=10) were restrained for one hour
      per day for 40 days; Group B animals (N=10) were restrained for one hour per day
      for three days; Group C (N=10) and Group D (N=8) animals were unrestrained. The
      upper left first molars in the rats in Groups A (long-term stress), B (short-term
      stress) and C (control) were moved mesially during the last 14 days of the
      experiment. The animals in Group D (N=8) were used for body weight and hormonal
      dosage comparisons only. They were not subjected to any stress and did not have
      appliances fitted. All animals were killed at 18 weeks of age and blood collected
      for measurement of plasma corticosterone. Tooth movement was measured with an
      electronic caliper. The right and left hemi-maxillae of five rats from each group
      were removed and the number of tartrate-resistant acid phosphatase (TRAP)
      positive cells, defined as osteoclasts, adjacent to the mesial roots of the upper
      first molars counted. The contralateral side in each animal served as the control
      (split-mouth design). RESULTS: Corticosterone levels were significantly higher in
      the stressed groups (Groups A and B) than in the control group (Group C). Tooth
      movement was significantly greater in Group A (long-term stress) compared with
      Group B (short-term stress) and Group C (control), which did not differ from each
      other. There were significantly more osteoclasts in the long-term stress group
      than in the short-term stress and control groups. CONCLUSION: Persistent systemic
      stress increases bone resorption during orthodontic tooth movement. Systemic
      stress may affect the rate of tooth movement during orthodontic treatment.

PMID- 19113078
TI  - Tooth size discrepancies in female patients with palatally impacted canines.
AB  - BACKGROUND: Small upper lateral incisors in patients with palatally impacted
      canines may contribute to inter-arch tooth size discrepancies. AIM: To compare
      the Bolton ratios in female patients with and without unilateral palatally
      impacted canines. METHODS: The pretreatment dental casts of 30 female patients
      with unilateral palatally impacted canines (Impaction group) and 30 female
      patients without palatally impacted canines (Control group) were used. The latter
      were matched for age and incisor malocclusion with the Impaction group. The
      anterior and overall Bolton ratios were calculated for each group. RESULTS:
      Although the total width of the upper anterior teeth in the impaction group was
      significantly smaller than the total width of the upper anterior teeth in the
      Control group (p = 0.029), there was no significant difference between the mesio
      distal widths of the lower anterior teeth in the two groups. Furthermore, there
      were no significant group differences in either the mean anterior Bolton ratio (p
      = 0.156) or the overall Bolton ratio (p = 0.652). CONCLUSION: Females patients
      with palatally impacted canines may not have more inter-arch tooth size
      discrepancies than female patients without palatally impacted canines.

PMID- 19113079
TI  - Clinical effects associated with miniscrews used as orthodontic anchorage.
AB  - AIMS: To measure the clinical effects associated with miniscrew anchorage used to
      retract the upper anterior teeth, specifically the positional changes associated
      with the miniscrews, the upper anterior teeth and the first upper molars.
      METHODS: This clinical trial included 13 patients. After orthodontic alignment,
      miniscrews were inserted in the maxillary zygomatic buttresses as anchorage for
      en masse retraction of the upper anterior teeth. Following premolar extractions,
      nickel-titanium closed coil springs, stretched between the miniscrews and upper
      archwire, were used for retraction. Three-dimensional changes in the upper
      anterior teeth, the upper first molars and the heads of the miniscrews were
      measured on study models taken before a 300 g force was applied and seven months
      later, or when retraction was completed if less than seven months. RESULTS: The
      mean duration of retraction was 5.23 months (SD: 1.74 months) with a range of
      three to seven months. The mean amount of anterior retraction was 3.82 +/- 1.64
      mm (Range: 0.77-7.07 mm). Average movements of the miniscrew heads on the right
      side were 0.44 mm buccally, 0.38 mm forward and 0.54 mm downward, and on the left
      side 0.06 mm buccally, 0.41 mm forward and 0.50 mm downward. During the study
      period the right and left upper first molars moved mesially 0.70 +/- 0.46 mm
      (Range: 0.01-2.3 mm) and 0.76 +/- 0.47 mm (Range: 0.1-2.61 mm) respectively,
      although no force was applied to them. CONCLUSION: Miniscrews provide
      satisfactory anchorage for retraction of the upper anterior segment, but do not
      remain absolutely stationary under orthodontic loads. Because of coincidental
      mesial movement of the upper molars, there must be sufficient clearance mesial to
      the molars to avoid the molar roots contacting the miniscrews.

PMID- 19113080
TI  - Risk factors and indications of orthodontic temporary anchorage devices: a
      literature review.
AB  - AIMS: The aims of this review are twofold, firstly, to give an overview of the
      general and local risk factors when using temporary anchorage devices (TADs) and
      the prerequisites for placement and, secondly, to illustrate the orthodontic
      indications of various TADs. METHODS: The PubMed database was searched for
      original articles on: 'orthodontics and miniscrews/mini-implants/
      miniplates/temporary anchorage devices/titanium screws/skeletal anchorage',
      'miniscrews/mini-implants/miniplates and risk factors/biomechanics/placement
      procedure'. Only articles published between 2001 and December 2007 were used. In
      addition, each article was hand searched for references that may have been missed
      by the PubMed search. RESULTS: General risk factors are factors concerning
      general health. Bone quality and oral hygiene are local risk factors. Aspects of
      the placement procedure discussed were: primary stability, loading protocols, pre
      drilling diameter and whether or not to make an intra-oral incision. A selection
      of published case reports is given to illustrate some orthodontic indications of
      TADs. CONCLUSIONS: Temporary anchorage devices have a place in modern
      orthodontics. Careful treatment planning involving radiographic examination is
      essential. Consultation with an oral surgeon is advisable if a soft tissue flap
      is required. Excellent patient compliance, particularly avoidance of inflammation
      around the implant, is an important consideration for successful use of TADs.

PMID- 19113081
TI  - Assisted eruption of impacted teeth into an alveolar bone graft in a patient with
      cleft lip and palate.
AB  - AIMS: To assist the eruption of impacted upper teeth into an alveolar bone graft
      in a patient with a unilateral cleft lip and palate. METHODS: An 8-year-old Thai
      boy with left unilateral complete cleft lip and palate had the chief complaint of
      anterior crossbite. He presented with a mild skeletal 3, dental Class III
      subdivision malocclusion, anterior crossbite, left unilateral posterior
      crossbite, moderate crowding in the upper arch with impaction of upper the left
      lateral incisor (tooth 22) and canine (tooth 23). In the first phase of treatment
      the posterior crossbite was corrected with a removable appliance with a 3-way
      screw. In the second phase the impacted teeth were surgically exposed, moved into
      the alveolar bone graft and the teeth aligned with fixed appliances. The upper
      left lateral incisor was extracted because of its questionable longevity.
      RESULTS: The orthodontic treatment resulted in normal overjet, overbite and an
      acceptable facial profile. A prosthesis replaced tooth 22. CONCLUSIONS: Forced
      eruption of impacted teeth can be carried out successfully in the cleft patients
      after an appropriate treatment plan has been formulated and following preparation
      of alveolar bone graft in the cleft site.

PMID- 19113082
TI  - Treatment of severe bimaxillary protrusion with miniscrew anchorage: treatment
      and complications.
AB  - BACKGROUND: Problems involving excessive face height and severe bimaxillary
      protrusion are usually treated with orthognathic surgery. When this form of
      treatment is rejected, retraction and intrusion of the anterior teeth using
      skeletal anchorage afforded by miniscrews may be employed. AIMS: To describe the
      treatment of severe bimaxillary protrusion with the aid of miniscrews and to
      discuss the complications encountered during treatment. METHODS: Following
      extraction of the four first premolars, miniscrews were placed bilaterally in
      both jaws to permit maximum retraction of the anterior teeth, and intrusion of
      the posterior and upper anterior teeth. RESULTS: The upper incisors were
      retracted 12 mm and intruded 5 mm over 20 months. The mandible rotated forward
      and upward, the face height reduced and the facial aesthetics improved. During
      treatment an irregular ridge of bone developed labial to the upper incisors, bone
      was deposited in the incisive fossae and the apices of the upper incisors were
      resorbed. An alveoloplasty was carried out to recontour the labial bone and the
      incisive fossae. CONCLUSIONS: Absolute anchorage provided by miniscrews may
      become an effective alternative to orthognathic surgery for treatment of severe
      bimaxillary protrusion. During extensive retraction, the teeth may contact
      structures not normally encountered during conventional orthodontic treatment.

PMID- 19113083
TI  - Risks and complications.

PMID- 19113084
TI  - Kerr constant and third-order nonlinear optic susceptibility measurements in a
      liquid crystal composed of bent-shaped molecules.
AB  - We report the determination of the Kerr constant (B) and the real part of the
      third-order nonlinear optic susceptibility (chi(3)) above the nematic-isotropic
      phase transition temperature (TNI) of a liquid crystal composed of bent-shaped
      molecules. The values of B and chi(3) just above (approximately 0.3 degrees C)
      TNI are approximately 8x10(-12) m/V2 and 5x10(-20) m2/V2, respectively. The
      estimated critical temperature TC* is about 1.5 degrees C below TNI indicating
      that the nematic-isotropic (NI) transition is weakly first order as in the case
      of calamitic liquid crystals. The temperature-dependent Kerr constant is found to
      be in good agreement with the predictions of the Landau-de Gennes theory. The
      experimental results are compared with those in a calamitic liquid crystal
      material with negative dielectric anisotropy in the nematic phase.

PMID- 19113085
TI  - Microvoid formation and strain hardening in highly cross-linked polymer networks.
AB  - Using molecular dynamics simulations of a generic model, we observe strain
      hardening in highly cross-linked polymer glasses under tensile deformation. We
      show that formation of microvoids, without bond breaking, constitutes the
      microscopic origins of strain hardening. A well-defined functional form is
      observed for the void size distribution that is consistent with voids in dense
      equilibrium Lennard-Jones particle packings, independent of strain. Microvoid
      based strain hardening is not observed in a separate model with tetrahedral bond
      angle constraints, indicating that flexible cross-linkers are the key factor in
      the development of strain hardening behavior.

PMID- 19113086
TI  - Dynamical scaling exponents for polymer translocation through a nanopore.
AB  - We determine the scaling exponents of polymer translocation (PT) through a
      nanopore by extensive computer simulations of various microscopic models for
      chain lengths extending up to N=800 in some cases. We focus on the scaling of the
      average PT time tau approximately Nalpha and the mean-square change of the PT
      coordinate, <s2(t)> approximately tbeta. We find alpha=1+2nu and beta=2/alpha for
      unbiased PT in two dimensions (2D) and three dimensions (3D). The relation
      alphabeta=2 holds for driven PT in 2D, with a crossover from alpha approximately
      2nu for short chains to alpha approximately 1+nu for long chains. This crossover
      is, however, absent in 3D where alpha=1.42+/-0.01 and alphabeta approximately 2.2
      for N approximately 40-800.

PMID- 19113087
TI  - Spatially correlated fluctuations and coherence dynamics in photosynthesis.
AB  - Recent multicolor photon-echo experiments revealed a long-lasting quantum
      coherence between excitations on the donor and acceptor in photosynthetic
      systems. Identifying the origin of the quantum coherence is essential to fully
      understand photosynthesis. Here we present a generic model in which a strong
      intermolecular steric restoring force in densely packed pigment-protein complexes
      results in a spatial correlation in conformational (static) variations of
      chromophores, which in turn induces an effective coupling between high-frequency
      (dynamic) fluctuations in donor and acceptor. The spatially correlated static and
      dynamic fluctuations provide a favorable environment to maintain quantum
      coherence, which can consistently explain the photon-echo measurements.

PMID- 19113088
TI  - Oscillations and patterns in interacting populations of two species.
AB  - Interacting populations often create complicated spatiotemporal behavior, and
      understanding it is a basic problem in the dynamics of spatial systems. We study
      the two-species case by simulations of a host-parasitoid model. In the case of
      coexistence, there are spatial patterns leading to noise-sustained oscillations.
      We introduce a measure for the patterns, and explain the oscillations as a
      consequence of a time-scale separation and noise. They are linked together with
      the patterns by letting the spreading rates depend on instantaneous population
      densities. Applications are discussed.

PMID- 19113089
TI  - Superstatistical distributions from a maximum entropy principle.
AB  - We deal with a generalized statistical description of nonequilibrium complex
      systems based on least biased distributions given some prior information. A
      maximum entropy principle is introduced that allows for the determination of the
      distribution of the fluctuating intensive parameter beta of a superstatistical
      system, given certain constraints on the complex system under consideration. We
      apply the theory to three examples: the superstatistical quantum-mechanical
      harmonic oscillator, the superstatistical classical ideal gas, and velocity time
      series as measured in a turbulent Taylor-Couette flow.

PMID- 19113090
TI  - Maximum distributions of bridges of noncolliding Brownian paths.
AB  - One-dimensional Brownian motion starting from the origin at time t=0 ,
      conditioned to return to the origin at time t=1 and to stay positive during time
      interval 0<t<1, is called the Bessel bridge with duration 1. We consider an N
      particle system of such Bessel bridges conditioned never to collide with each
      other in 0<t<1, which is the continuum limit of the vicious walk model in
      watermelon configuration with a wall. Distributions of maximum values of paths
      attained in the time interval t epsilon (0,1) are studied to characterize the
      statistics of random patterns of the repulsive paths on the spatiotemporal plane.
      For the outermost path, the distribution function of maximum value is exactly
      determined for general N. We show that the present N-path system of noncolliding
      Bessel bridges is realized as the positive-eigenvalue process of the 2Nx2N matrix
      valued Brownian bridge in the symmetry class C. Using this fact, computer
      simulations are performed and numerical results on the N dependence of the
      maximum-value distributions of the inner paths are reported. The present work
      demonstrates that the extreme-value problems of noncolliding paths are related to
      random matrix theory, the representation theory of symmetry, and number theory.

PMID- 19113091
TI  - Kinetics of self-induced aggregation of Brownian particles: non-Markovian and non
      Gaussian features.
AB  - In this paper we have explored a model for self-induced aggregation of Brownian
      particles incorporating non-Markovian and non-Gaussian character of the
      associated random noise processes. The time evolution of each individual is
      guided by an overdamped Langevin equation of motion with a nonlocal drift arising
      out of the imbalance in the local distribution of the other individuals. Our
      simulation results show that colored noise enhances the tendency of cluster
      formation. Another observation is that the critical noise variance decreases at
      first with increase in noise correlation time followed by an increase after
      exhibiting a minimum. Furthermore, in the long time limit the cluster number in
      the aggregation process exhibits depletion with time following a power law with
      an exponent which increases remarkably with non-Markovian character of the noise
      processes.

PMID- 19113092
TI  - Joint probability distributions and multipoint correlations of the continuous
      time random walk.
AB  - We present an efficient method to determine the Fourier-Laplace transform of the
      joint n-point probability distribution of a continuous-time random walk for
      arbitrary finite n. Additionally, we devise a recursive procedure with which it
      is possible to calculate the Laplace transforms of the multipoint correlation
      functions without having to determine the joint probability distributions first.
      The methods are used on several examples with both independent and dependent
      distributions for the waiting time and the spatial step size.

PMID- 19113093
TI  - Percolation on correlated networks.
AB  - We reconsider the problem of percolation on an equilibrium random network with
      degree-degree correlations between nearest-neighboring vertices focusing on
      critical singularities at a percolation threshold. We obtain criteria for degree
      degree correlations to be irrelevant for critical singularities. We present
      examples of networks in which assortative and disassortative mixing leads to
      unusual percolation properties and new critical exponents.

PMID- 19113094
TI  - Diffusion and relaxation controlled by tempered alpha-stable processes.
AB  - We derive general properties of anomalous diffusion and nonexponential relaxation
      from the theory of tempered alpha-stable processes. The tempering results in the
      existence of all moments of operational time. The subordination by the inverse
      tempered alpha-stable process provides diffusion (relaxation) that occupies an
      intermediate place between subdiffusion (Cole-Cole law) and normal diffusion
      (exponential law). Here we obtain explicitly the Fokker-Planck equation and the
      Cole-Davidson relaxation function. This model includes subdiffusion as a
      particular case.

PMID- 19113095
TI  - Transport coefficients of non-Newtonian fluid and causal dissipative
      hydrodynamics.
AB  - A formula to calculate the transport coefficients of the causal dissipative
      hydrodynamics is derived by using the projection operator method (Mori-Zwanzig
      formalism) [T. Koide, Phys. Rev. E 75, 060103(R) (2007)]. This is an extension of
      the Green-Kubo-Nakano (GKN) formula to the case of non-Newtonian fluids, which is
      the essential factor to preserve the relativistic causality in relativistic
      dissipative hydrodynamics. This formula is the generalization of the GKN formula
      in the sense that it can reproduce the GKN formula in a certain limit. In this
      work, we extend the previous work so as to apply to more general situations.

PMID- 19113096
TI  - Dynamic phase transition in the two-dimensional kinetic Ising model in an
      oscillating field: universality with respect to the stochastic dynamics.
AB  - We study the dynamical response of a two-dimensional Ising model subject to a
      square-wave oscillating external field. In contrast to earlier studies, the
      system evolves under a so-called soft Glauber dynamic [Rikvold and Kolesik, J.
      Phys. A 35, L117 (2002)], for which both nucleation and interface propagation are
      slower and the interfaces smoother than for the standard Glauber dynamic. We
      choose the temperature and magnitude of the external field such that the
      metastable decay of the system following field reversal occurs through nucleation
      and growth of many droplets of the stable phase, i.e., the multidroplet regime.
      Using kinetic Monte Carlo simulations, we find that the system undergoes a
      nonequilibrium phase transition, in which the symmetry-broken dynamic phase
      corresponds to an asymmetric stationary limit cycle for the time-dependent
      magnetization. The critical point is located where the half period of the
      external field is approximately equal to the metastable lifetime of the system.
      We employ finite-size scaling analysis to investigate the characteristics of this
      dynamical phase transition. The critical exponents and the fixed-point value of
      the fourth-order cumulant are found to be consistent with the universality class
      of the two-dimensional equilibrium Ising model. This universality class has
      previously been established for the same nonequilibrium model evolving under the
      standard Glauber dynamic, as well as in a different nonequilibrium model of CO
      oxidation. The results reported in the present paper support the hypothesis that
      this far-from-equilibrium phase transition is universal with respect to the
      choice of the stochastic dynamics.

PMID- 19113097
TI  - Switching-path distribution in multidimensional systems.
AB  - We explore the distribution of paths followed in fluctuation-induced switching
      between coexisting stable states. We introduce a quantitative characteristic of
      the path distribution in phase space that does not require a priori knowledge of
      system dynamics. The theory of the distribution is developed and its direct
      measurement is performed in a micromechanical oscillator driven into parametric
      resonance. The experimental and theoretical results on the shape and position of
      the distribution are in excellent agreement, with no adjustable parameters. In
      addition, the experiment provides the first demonstration of the lack of time
      reversal symmetry in switching of systems far from thermal equilibrium. The
      results open the possibility of efficient control of the switching probability
      based on the measured narrow path distribution.

PMID- 19113098
TI  - Anisotropic rotational diffusion and dielectric relaxation of rigid dipolar
      particles in a strong external dc field.
AB  - Dielectric response functions of polar particles (macromolecules) diluted in a
      nonpolar solvent subjected to a strong external dc electric field are evaluated
      using the anisotropic noninertial rotational diffusion model. Simple analytic
      formulas for the longitudinal and transverse components of the dielectric
      susceptibility and relaxation times are given using the effective relaxation time
      method. These formulas are tested against numerical solutions of the underlying
      infinite hierarchy of differential-recurrence equations for statistical moments
      (ensemble averages of the Wigner D functions) which are obtained by averaging the
      governing Langevin equation for noninertial rotational Brownian motion over its
      realizations. The calculations, involving matrix continued fractions, ultimately
      yield the exact solution of the infinite hierarchy of differential-recurrence
      relations for the dielectric response functions. In the isotropic rotational
      diffusion limit, the solution reduces to the known results.

PMID- 19113099
TI  - Narrow escape and leakage of Brownian particles.
AB  - Questions of flux regulation in biological cells raise a renewed interest in the
      narrow escape problem. The determination of a higher order asymptotic expansion
      of the narrow escape time depends on determining the singularity behavior of the
      Neumann Green's function for the Laplacian in a three-dimensional (3D) domain
      with a Dirac mass on the boundary. In addition to the usual 3D Coulomb
      singularity, this Green's function also has an additional weaker logarithmic
      singularity. By calculating the coefficient of this logarithmic singularity, we
      calculate the second term in the asymptotic expansion of the narrow escape time
      and in the expansion of the principal eigenvalue of the Laplace equation with
      mixed Dirichlet-Neumann boundary conditions, with small Dirichlet and large
      Neumann parts. We also determine the leakage flux of Brownian particles that
      diffuse from a source to an absorbing target on a reflecting boundary of a
      domain, if a small perforation is made in the reflecting boundary.

PMID- 19113100
TI  - Role of pinning potentials in heat transport through disordered harmonic chains.
AB  - The role of quadratic on-site pinning potentials on determining the size (N)
      dependence of the disorder averaged steady state heat current J in an
      isotopically disordered harmonic chain connected to stochastic heat baths is
      investigated. For two models of heat baths, namely white noise baths and Rubin's
      model of baths, we find that the N dependence of J is the same and depends on the
      number of pinning centers present in the chain. In the absence of pinning, <J>Fr
      approximately 1/N1/2 while in the presence of one or two pins <J>Fi approximately
      1/N3/2. For a finite (n) number of pinning centers with 2<or=n<<N we provide
      heuristic arguments and numerical evidence to show that <J>n approximately 1/N(n
      1/2). We discuss the relevance of our results in the context of recent
      experiments.

PMID- 19113101
TI  - Return interval distribution of extreme events and long-term memory.
AB  - The distribution of recurrence times or return intervals between extreme events
      is important to characterize and understand the behavior of physical systems and
      phenomena in many disciplines. It is well known that many physical processes in
      nature and society display long-range correlations. Hence, in the last few years,
      considerable research effort has been directed towards studying the distribution
      of return intervals for long-range correlated time series. Based on numerical
      simulations, it was shown that the return interval distributions are of stretched
      exponential type. In this paper, we obtain an analytical expression for the
      distribution of return intervals in long-range correlated time series which holds
      good when the average return intervals are large. We show that the distribution
      is actually a product of power law and a stretched exponential form. We also
      discuss the regimes of validity and perform detailed studies on how the return
      interval distribution depends on the threshold used to define extreme events.

PMID- 19113102
TI  - Injected power fluctuations in one-dimensional dissipative systems: role of
      ballistic transport.
AB  - This paper is a generalization of the models considered in J. Stat. Phys. 128,
      1365 (2007). Using an analogy with free fermions, we compute exactly the large
      deviation function (LDF) of the energy injected up to time t in a one-dimensional
      dissipative system of classical spins, where a drift is allowed. The dynamics are
      T=0 asymmetric Glauber dynamics driven out of rest by an injection mechanism,
      namely, a Poissonian flipping of one spin. The drift induces anisotropy in the
      system, making the model more comparable to experimental systems with dissipative
      structures. We discuss the physical content of the results, specifically the
      influence of the rate of the Poisson injection process and the magnitude of the
      drift on the properties of the LDF. We also compare the results of this spin
      model to simple phenomenological models of energy injection (Poisson or Bernoulli
      processes of domain wall injection). We show that many qualitative results of the
      spin model can be understood within this simplified framework.

PMID- 19113103
TI  - Anomalous diffusion in heterogeneous glass-forming liquids: temperature-dependent
      behavior.
AB  - In a preceding paper, Langer and Mukhopadhyay [Phys. Rev. E 77, 061505 (2008)]
      studied the diffusive motion of a tagged molecule in an heterogeneous glass
      forming liquid at temperatures just above a glass transition. Among other
      features of this system, we postulated a relation between heterogeneity and
      stretched-exponential decay of correlations, and we also confirmed that systems
      of this kind generally exhibit non-Gaussian diffusion on intermediate length and
      time scales. Here I extend this analysis to higher temperatures approaching the
      point where the heterogeneities disappear and thermal activation barriers become
      small. I start by modifying the continuous-time random-walk theory proposed in
      Langer and Mukhopadhyay and supplement this analysis with an extension of the
      excitation-chain theory of glass dynamics. I also use a key result from the shear
      transformation-zone theory of viscous deformation of amorphous materials.
      Elements of each of these theories are then used to interpret experimental data
      for orthoterphenyl, specifially, the diffusion and viscosity coefficients and
      neutron-scattering measurements of the self-intermediate scattering function.
      Reconciling the theory with these data sets provides insights into the crossover
      between super-Arrhenius and Arrhenius dynamics, length scales of spatial
      heterogeneities, violation of the Stokes-Einstein relation in glass-forming
      liquids, and the origin of stretched-exponential decay of correlations.

PMID- 19113104
TI  - Langevin formulation for single-file diffusion.
AB  - We introduce a stochastic equation for the microscopic motion of a tagged
      particle in the single-file model. This equation provides a compact
      representation of several of the system's properties such as fluctuation
      dissipation and linear-response relations, achieved by means of a diffusion noise
      approach. Most importantly, the proposed Langevin equation reproduces
      quantitatively the three temporal regimes and the corresponding time scales:
      ballistic, diffusive, and subdiffusive.

PMID- 19113105
TI  - Scaling properties of a rice-pile model: inertia and friction effects.
AB  - We present a rice-pile cellular automaton model that includes inertial and
      friction effects. This model is studied in one dimension, where the updating of
      metastable sites is done according to a stochastic dynamics governed by a
      probabilistic toppling parameter p that depends on the accumulated energy of
      moving grains. We investigate the scaling properties of the model using finite
      size scaling analysis. The avalanche size, the lifetime, and the residence time
      distributions exhibit a power-law behavior. Their corresponding critical
      exponents, respectively, tau, y, and yr, are not universal. They present
      continuous variation versus the parameters of the system. The maximal value of
      the critical exponent tau that our model gives is very close to the experimental
      one, tau=2.02 [Frette, Nature (London) 379, 49 (1996)], and the probability
      distribution of the residence time is in good agreement with the experimental
      results. We note that the critical behavior is observed only in a certain range
      of parameter values of the system which correspond to low inertia and high
      friction.

PMID- 19113106
TI  - Scaling exponents and transition behavior of the generalized conserved lattice
      gas model at zero temperature.
AB  - We study a generalized conserved lattice gas model in two dimensions by
      introducing an effective temperature to the conserved lattice gas model, where
      the number of particles is conserved during the dynamical process. We apply Monte
      Carlo simulation with the Metropolis transition rate. At zero temperature we find
      two transition behaviors; one between the localized active states and absorbing
      states and the other between the localized active states and active states. With
      a different definition of the order parameter for the second transition behavior,
      we obtain the critical exponents at the transition point.

PMID- 19113107
TI  - Equilibrium long-ranged charge correlations at the surface of a conductor coupled
      to electromagnetic radiation.
AB  - This study is related to the fluctuation theory of electromagnetic fields,
      charges, and currents. The three-dimensional system under consideration is a semi
      infinite conductor, modeled by the jellium, in vacuum. In previous theoretical
      studies it was found that the correlation functions of the surface charge density
      on the conductor decay as the inverse cube of the distance at asymptotically
      large distances. The prefactor to this asymptotic decay was obtained in the
      classical limit and in the quantum case without retardation effects. To describe
      the retarded regime, we study a more general problem of the semi-infinite jellium
      in thermal equilibrium with the radiated electromagnetic field. By using Rytov's
      fluctuational electrodynamics we show that, for both static and time-dependent
      surface charge correlation functions, the inclusion of retardation effects causes
      the quantum prefactor to take its universal static classical form, for any
      temperature.

PMID- 19113108
TI  - Interaction stochasticity supports cooperation in spatial Prisoner's dilemma.
AB  - Previous studies mostly assume deterministic interactions among neighboring
      individuals for games on graphs. In this paper, we relax this assumption by
      introducing stochastic interactions into the spatial Prisoner's dilemma game, and
      study the effects of interaction stochasticity on the evolution of cooperation.
      Interestingly, simulation results show that there exists an optimal region of the
      intensity of interaction resulting in a maximum cooperation level. Moreover, we
      find good agreement between simulation results and theoretical predictions
      obtained from an extended pair-approximation method. We also show some typical
      snapshots of the system and investigate the mean payoffs for cooperators and
      defectors. Our results may provide some insight into understanding the emergence
      of cooperation in the real world where the interactions between individuals take
      place in an intermittent manner.

PMID- 19113109
TI  - Effect of a time-dependent field on subdiffusing particles.
AB  - We analyze the effect of a time-dependent external field on non-Markovian
      migration described by the continuous time random walk (CTRW) approach. The
      rigorous method of treating the problem is proposed which is based on the
      Markovian representations of the CTRW approach and field modulation. With the use
      of this method we derive the non-Markovian stochastic Liouville equation (SLE),
      that describes the effect of this field, and thoroughly analyze the relation of
      the derived SLE with equations proposed earlier. This SLE is applied to the case
      of subdiffusive migration in which the exact formulas for the first and second
      moments of spatial distribution are obtained. In the case of oscillating external
      field they predict unusual dependence of the first moment on oscillation phase
      and anomalous time behavior of field dependent contribution to the dispersion
      which agree with results of earlier works. Anomalous time dependence is also
      found in the case of a fluctuating field. The specific features of this time
      dependence are analyzed in detail.

PMID- 19113110
TI  - Thermally activated switching in the presence of non-Gaussian noise.
AB  - We study the effect of a non-Gaussian noise on interstate switching activated
      primarily by Gaussian noise. Even weak non-Gaussian noise can strongly change the
      switching rate. The effect is determined by all moments of the noise
      distribution. It is expressed in a closed form in terms of the noise
      characteristic functional. The analytical results are compared with the results
      of simulations for an overdamped system driven by white Gaussian noise and a
      Poisson noise. Switching induced by a purely Poisson noise is also discussed.

PMID- 19113111
TI  - Increase of Boltzmann entropy in a quantum forced harmonic oscillator.
AB  - Recently, a quantum-mechanical proof of the increase of Boltzmann entropy in
      quantum systems that are coupled to an external classical source of work has been
      given. Here we illustrate this result by applying it to a forced quantum harmonic
      oscillator. We show plots of the actual temporal evolution of work and entropy
      for various forcing protocols. We note that entropy and work can be partially or
      even fully returned to the source, although both work and entropy balances are
      non-negative at all times in accordance with the minimal work principle and the
      Clausius principle, respectively. A necessary condition for the increase of
      entropy is that the initial distribution is decreasing (e.g., canonical). We show
      evidence that for a nondecreasing distribution (e.g., microcanonical), the
      quantum expectation of entropy may decrease slightly. Interestingly, the
      classical expectation of entropy cannot decrease, irrespective of the initial
      distribution, in the forced harmonic oscillator.

PMID- 19113112
TI  - Effect of asymmetry in a binary state on the collective behavior of a system with
      spatially modulated interaction and quenched randomness.
AB  - The properties of solid states, biophysical materials, neuronal circuits, and
      equilibrium states of a many-body system can be studied by using techniques in
      statistical physics. It has been common practice to represent a system composed
      of binary state units by using an Ising spin network where each unit has
      symmetric {-1,1} states. However, the asymmetry or symmetry of the binary states
      of the units can affect the property and ergodicity of the system, but better
      understanding of the quantitative difference is still needed. We compare systems
      of binary units with symmetric or asymmetric states. The network has spatially
      modulated interaction with quenched randomness. We can bridge the Ising spin
      network and McCulloch-Pitts neuron network and analyze the stability of the
      system via replica method by introducing an interpolating parameter. The effects
      of the asymmetry states affect the multistability of the system and the stability
      of replica-symmetry solutions.

PMID- 19113113
TI  - Resonant transport in pulsated devices: mobility oscillations and diffusion
      peaks.
AB  - Diffusion of an overdamped Brownian particle on a symmetric periodic substrate is
      investigated in the presence of pulsated perturbations of two kinds: (i) Stepwise
      lateral displacements (flashing substrate) and (ii) instantaneous tilts (shot
      noise). Pulses are applied, as it is often observed, in either periodic or random
      sequences with assigned mean (bias) and average waiting time (time constant). For
      a given bias, both the diffusion coefficient and the mobility of the particle can
      be greatly enhanced by tuning the time constant. Moreover, also depending on the
      time constant, the mobility can grow negative in (i) or exceed unity in (ii). We
      term this phenomenon resonant transport.

PMID- 19113114
TI  - Reduced fidelity susceptibility and its finite-size scaling behaviors in the
      Lipkin-Meshkov-Glick model.
AB  - We derive a general formula for the reduced fidelity susceptibility when the
      reduced density matrix is 2x2 block diagonal. By using this result and a
      continuous unitary transformation, we study finite-size scaling of the reduced
      fidelity susceptibility in the Lipkin-Meshkov-Glick model. It is found that it
      can well characterize quantum phase transitions, that is, we can extract
      information about quantum phase transitions from only the fidelity of a
      subsystem, which is of practical use in experiments.

PMID- 19113115
TI  - Modeling temporal fluctuations in avalanching systems.
AB  - We demonstrate how to model the toppling activity in avalanching systems by
      stochastic differential equations (SDEs). The theory is developed as a
      generalization of the classical mean-field approach to sandpile dynamics by
      formulating it as a generalization of Ito's SDE. This equation contains a
      fractional Gaussian noise term representing the branching of an avalanche into
      small active clusters and a drift term reflecting the tendency for small
      avalanches to grow and large avalanches to be constricted by the finite system
      size. If one defines avalanching to take place when the toppling activity exceeds
      a certain threshold, the stochastic model allows us to compute the avalanche
      exponents in the continuum limit as functions of the Hurst exponent of the noise.
      The results are found to agree well with numerical simulations in the Bak-Tang
      Wiesenfeld and Zhang sandpile models. The stochastic model also provides a method
      for computing the probability density functions of the fluctuations in the
      toppling activity itself. We show that the sandpiles do not belong to the class
      of phenomena giving rise to universal non-Gaussian probability density functions
      for the global activity. Moreover, we demonstrate essential differences between
      the fluctuations of total kinetic energy in a two-dimensional turbulence
      simulation and the toppling activity in sandpiles.

PMID- 19113116
TI  - Optimizing the encounter rate in biological interactions: Ballistic versus Levy
      versus Brownian strategies.
AB  - Bartumeus et al. [Phys. Rev. Lett. 88, 097901 (2002)] compared the efficiency of
      a Levy random walk predator strategy with a Brownian random walk strategy in a
      periodic one-dimensional domain with nonrevisitable moving targets. Their
      findings from numerical simulations conclude that "a Levy search strategy is the
      best option in some, but not all, cases for a random search process." Using the
      same methodology, we show that the simplest random search strategy of all,
      ballistic motion in a random direction, outperforms a Levy strategy in almost
      every case. We further show that, in the small set of cases where the ballistic
      strategy is not optimal, the periodic model does not capture the more realistic
      nonperiodic case. In the nonperiodic case, the ballistic strategy again
      outperforms the Levy strategy.

PMID- 19113117
TI  - Relation of water anomalies to the excess entropy.
AB  - Using the five-site transferable intermolecular potential (TIP5P) we perform
      molecular dynamics simulations to investigate the relationship between the excess
      entropy and anomalies of water. We find that the two-body excess entropy is an
      ideal quantity to predict the regions of structural, dynamic, and thermodynamic
      anomalies of water in its pressure-temperature and density-temperature phase
      diagrams. From the excess entropy we can also predict the location of the Widom
      line, associated with the hypothesized liquid-liquid critical point in
      supercooled water.

PMID- 19113118
TI  - Nonlocal viscous transport and the effect on fluid stress.
AB  - We demonstrate that, in general, only for fluid flows in which the gradient of
      the strain rate is constant or zero can the classical Navier-Stokes equations
      with constant transport coefficients be considered exact. This is typical of two
      of the most common types of flow: Couette and Poiseuille. For more complicated
      flow fields in which the streaming velocity involves higher order nonlinear
      terms, the use of nonlocal constitutive equations gives an exact description of
      the flow. These constitutive equations involve nonlocal transport kernels. For
      momentum transport we demonstrate that nonlocality will be significant for any
      particular flow field if the even moments of the nonlocal viscosity kernel are
      non-negligible. This corresponds to the condition that the strain rate varies
      appreciably over the width of the kernel in real space. Such conditions are
      likely to be dominant for nanofluidic flows.

PMID- 19113119
TI  - Effect of inelasticity on the phase transitions of a thin vibrated granular
      layer.
AB  - We describe an experimental and computational investigation of the ordered and
      disordered phases of a vibrating thin, dense granular layer composed of identical
      metal spheres. We compare the results from spheres with different amounts of
      inelasticity and show that inelasticity has a strong effect on the phase diagram.
      We also report the melting of an ordered phase to a homogeneous disordered liquid
      phase at high vibration amplitude or at large inelasticities. Our results show
      that dissipation has a strong effect on ordering and that in this system ordered
      phases are absent entirely in highly inelastic materials.

PMID- 19113120
TI  - Decompaction and fluidization of a saturated and confined granular medium by
      injection of a viscous liquid or gas.
AB  - We compare quantitatively two experimental situations concerning injection of a
      miscible fluid into an initially jammed granular medium saturated with the same
      fluid, confined in a Hele-Shaw cell. The two experiments are identical, apart
      from the interstitial and injected fluid, which is in one case air injected into
      a dry granular packing, and in the other case silicone oil injected into a dense
      suspension. In spite of the strong differences regarding the nature of the two
      fluids, strikingly similar dynamical and geometrical features are identified as
      functions of the control parameters: cell thickness and applied fluid injection
      pressure. In both cases an initial hydrodynamically driven decompaction process
      controls the unjamming and prepares the final displacement process characterized
      by fingerlike patterns empty of grains. The pattern shapes are comparable. In
      addition, the mobilities of the coupled fluid-grain flow, rescaled by the
      interstitial fluid viscosity and grain diameter squared, are of the same range
      and behave comparably. The mobility proves to depend on the initial solid
      fraction of the medium. Subtle differences are observed in geometrical aspects
      like the finger width with respect to the control parameters.

PMID- 19113121
TI  - Short-pulse dynamics in strongly nonlinear dissipative granular chains.
AB  - We study the energy decay properties of a pulse propagating in a strongly
      nonlinear granular chain with damping proportional to the relative velocity of
      the grains. We observe a wave disturbance that at low viscosities consists of two
      parts exhibiting two entirely different time scales of dissipation. One part is
      an attenuating solitary wave, dominated by discreteness and nonlinearity effects
      as in a dissipationless chain, and has the shorter lifetime. The other is a
      purely dissipative shocklike structure with a much longer lifetime and exists
      only in the presence of dissipation. The range of viscosities and initial
      configurations that lead to this complex wave disturbance are explored.

PMID- 19113122
TI  - Coefficient of restitution for viscoelastic spheres: the effect of delayed
      recovery.
AB  - The coefficient of normal restitution of colliding viscoelastic spheres is
      computed as a function of the material properties and the impact velocity. From
      simple arguments it becomes clear that, in a collision of purely repulsively
      interacting particles, the particles lose contact slightly before the distance of
      the centers of the spheres reaches the sum of the radii, that is, the particles
      recover their shape only after they lose contact with their collision partner.
      This effect was neglected in earlier calculations, which leads erroneously to
      attractive forces and thus to an underestimation of the coefficient of
      restitution. As a result we find a different dependence of the coefficient of
      restitution on the impact rate.

PMID- 19113123
TI  - Nonmonotonic reversible branch in four model granular beds subjected to vertical
      vibration.
AB  - We present results from four independent models of a granular assembly subjected
      to tapping. We find that the steady-state packing fraction as a function of the
      tapping intensity is nonmonotonic. In particular, for high tapping intensities,
      we observe an increase of the packing fraction with tapping strength. This
      finding challenges the current understanding of compaction of granular media
      since the steady-state packing fraction is believed to decrease monotonically
      with increasing tapping intensity. We propose an explanation of our results based
      on the properties of the arches formed by the particles.

PMID- 19113124
TI  - Elastic properties of hollow colloidal particles.
AB  - The elastic properties of micrometer-sized hollow colloidal particles obtained by
      emulsion templating are probed by nanoindentation measurements in which point
      forces are applied to solvent-filled particles supported on a flat substrate. We
      show that the shells respond linearly up to forces of 7-21 nN, where the
      indentation becomes of the order of the shell thickness (20-40 nm). In the linear
      region, the particle deformation is reversible. The measured Young's modulus
      (approximately 200 MPa) is comparable to values for stiff rubbers or soft
      polymers. At larger applied force, we observe a crossover into a nonlinear
      regime, where the shells assume a buckled shape. Here, the force increases
      approximately as the square root of the indentation, in agreement with the theory
      of elasticity of thin shells. We also observe permanent deformation of the shells
      after probing them repetitively beyond the linear regime. Finally, the measured
      elastic properties of the shells nicely explain their spontaneous buckling in
      solution and due to drying.

PMID- 19113125
TI  - Exhaustion of nucleation in a closed system.
AB  - We determine the distribution of cluster sizes that emerges from an initial phase
      of homogeneous aggregation with conserved total particle density. The physical
      ingredients behind the predictions are essentially classical: Supercritical
      nuclei are created at the Zeldovich rate, and before the depletion of monomers is
      significant, the characteristic cluster size is so large that the clusters
      undergo diffusion-limited growth. Mathematically, the distribution of cluster
      sizes satisfies an advection partial differential equation (PDE) in "size space."
      During this creation phase, clusters are nucleated and then grow much larger than
      the critical size, so nucleation of supercritical clusters at the Zeldovich rate
      is represented by an effective boundary condition at zero size. The advection PDE
      subject to the effective boundary condition constitutes a "creation signaling
      problem" for the evolving distribution of cluster sizes during the creation era.
      Dominant balance arguments applied to the advection signaling problem show that
      the characteristic time and cluster size of the creation era are exponentially
      large in the initial free-energy barrier against nucleation, G*. Specifically,
      the characteristic time is proportional to e(2/5)G*/kBT} and the characteristic
      number of monomers in a cluster is proportional to e(3/5)G*/kBT. The
      exponentially large characteristic time and cluster size give a posteriori
      validation of the mathematical signaling problem. In a short note, Marchenko
      [JETP Lett. 64, 66 (1996)] obtained these exponentials and the numerical
      prefactors 2/5 and 3/5. Our work adds the actual solution of the kinetic model
      implied by these scalings, and the basis for connection to subsequent stages of
      the aggregation process after the creation era.

PMID- 19113126
TI  - Mesoscopic model for colloidal particles, powders, and granular solids.
AB  - A simulation model is presented, comprising elastic spheres with a short-range
      attraction. Besides conservative forces, radial and shear friction, and radial
      noise are added. The model can be used to simulate colloids, granular solids, and
      powders, and the parameters may be related to experimental systems via the range
      of attraction and the adhesion energy. The model shares the simplicity and speed
      of dissipative particle dynamics, yet the predictions are rather nontrivial. We
      demonstrate that the model predicts the correct scaling relations for fracture of
      granular solids, and we present a schematic phase diagram. This shows liquid
      vapor coexistence for a sufficiently large interaction range, with a surface
      tension that follows Ising criticality. For smaller interaction range only solid
      vapor coexistence is found, but for a very small attractive interaction range
      stable liquid-vapor coexistence reappears due to pathological stability of the
      solid phase. At very low temperature the model forms a glassy state.

PMID- 19113127
TI  - Cooperative activated dynamics in dense mixtures of hard and sticky spheres.
AB  - The coupled activated dynamics in dense mixtures of repulsive and sticky hard
      spheres is studied using stochastic nonlinear Langevin equation theory. The
      effective free energy surface, barriers, saddle point trajectories, and mean
      first passage times depend in a rich manner on mixture composition, (high) total
      volume fraction, and attractive interaction strength. In general, there are three
      types of saddle point trajectories or relaxation pathways: a pure sticky or pure
      repulsive particle displacement keeping the other species localized, and a
      cooperative motion involving repulsive and attractive particle displacements. The
      barrier for activated hopping usually increases with the ratio of sticky to
      repulsive particle displacement. However, at intermediate values of the
      displacement ratio it can attain a broad plateau value, and can even exhibit a
      local maximum, and hence nonmonotonic behavior, at high sticky particle mixture
      compositions if the attraction strength is modest. The mean first passage, or
      hopping, times are computed using multidimensional Kramers theory. In most cases
      the hopping time trends reflect the behavior of the barrier height, especially as
      the sticky particle attraction strengths become large. However, there are
      dramatic exceptions associated with cooperative repulsive and attractive particle
      trajectories where the barriers are high but a greatly enhanced number of such
      trajectories exist near the saddle point.

PMID- 19113128
TI  - Breakup of bubbles and drops in steadily sheared foams and concentrated
      emulsions.
AB  - This experimental study is focused on the process of bubble breakup in steadily
      sheared foams, at constant shear rate or constant shear stress. Two different
      types of surfactants were used and glycerol was added to the aqueous phase, to
      check how the bubble breakup depends on the surface modulus and on bulk viscosity
      of the foaming solutions. The experiments show that bubble breakup in foams
      occurs above a well defined critical dimensionless stress, tau[over]CR identical
      with(tauCRR/sigma) approximately 0.40, which is independent of surfactant used,
      solution viscosity, and bubble volume fraction (varied between 92 and 98%). Here
      tauCR is the dimensional shear stress, above which a bubble with radius R and
      surface tension sigma would break in sheared foam. The value of the critical
      stress experimentally found by us tau[over]CR approximately 0.40, is about two
      orders of magnitude lower than the critical stress for breakup of single bubbles
      in sheared Newtonian liquids, tau[over]CR approximately 25. This large difference
      in the critical stress is explained by the strong interaction between neighboring
      bubbles in densely populated foams, which facilitates bubble subdivision into
      smaller bubbles. A strong effect of bubble polydispersity on the kinetics of
      bubble breakup (at similar mean bubble size) was observed and explained.
      Experiments were also performed with hexadecane-in-water emulsions of drop volume
      fraction 83%<or=Phi<or=95% to study drop breakup in concentrated emulsions.
      Qualitatively similar behavior was observed to that of foams, with the critical
      dimensionless stress for drop breakup being lower, tau[over]CR approximately
      0.15, and practically independent of the drop volume fraction and viscosity ratio
      (varied between 0.01 and 1). This critical stress is by several times lower than
      the critical stress for breakage of single drops in sheared Newtonian fluids at
      comparable viscosity ratio, which evidences for facilitated drop subdivision in
      concentrated emulsions. To explain the measured low values of the critical
      stress, a different type of capillary instability of the breaking bubbles and
      drops in concentrated foams and emulsions is proposed and discussed.

PMID- 19113129
TI  - Thermodynamics of vesicle growth and instability.
AB  - We describe the growth of vesicles, due to the accretion of lipid molecules to
      their surface, in terms of linear irreversible thermodynamics. Our treatment
      differs from those previously put forward by consistently including the energy of
      the membrane in the thermodynamic description. We calculate the critical radius
      at which the spherical vesicle becomes unstable to a change of shape in terms of
      the parameters of the model. The analysis is carried out for the case both when
      the increase in volume is due to the absorption of water and when a solute is
      also absorbed through the walls of the vesicle.

PMID- 19113130
TI  - Suppression of the rate of growth of dynamic heterogeneities and its relation to
      the local structure in a supercooled polydisperse liquid.
AB  - The relationship between the microscopic arrangement of molecules in a
      supercooled liquid and its slow dynamics at low temperature near glass transition
      is studied by molecular dynamics simulations. A Lennard-Jones liquid with
      polydispersity in size and mass of constituent particles is chosen as the model
      system. Our studies reveal that the local structure (that varies with
      polydispersity) plays a crucial role both in the slowing down of dynamics and in
      the growth of the dynamic heterogeneities, besides determining the glass forming
      ability of the system. Increasing polydispersity at fixed volume fraction is
      found to suppress the rate of growth of dynamic correlations, as detected by the
      growth in the peak of the nonlinear density response function, chi4(t). The
      growth in dynamical correlation is manifested in a stronger than usual breakdown
      of Stokes-Einstein relation at lower polydispersity at low temperatures and also
      leads to a decrease in the fragility of the system with polydispersity. We show
      that the suppression of the rate of growth of the dynamic heterogeneity can be
      attributed to the loss of structural correlations (as measured by the structure
      factor and the local bond orientational order) with polydispersity. While a
      critical polydispersity is required to avoid crystallization, we find that a
      further increase in polydispersity lowers the glass forming ability.

PMID- 19113131
TI  - Magnetic-field-induced optical anisotropy in ferrofluids: a time-dependent light
      scattering investigation.
AB  - We report an experimental investigation of time dependent anisotropic light
      scattering by an aqueous suspension of tetramethyl ammonium hydroxide coated
      Fe3O4 nanoparticles (approximately 6 nm) under the ON-OFF transient of an
      external dc magnetic field. The study employs the synchronized recording and
      measurement of the two magnetic-field-induced light-scattering patterns produced
      by two identical orthogonal He-Ne laser beams passing through the ferrofluid
      sample and propagating parallel and perpendicular to the applied field,
      respectively. From these patterns, we extract the time dependence of the induced
      optical anisotropy, which provides a measure of the characteristic time scale and
      kinematic response for field-induced structure formation in the sample. We
      propose that the time evolution of the scattering patterns, which is very fast at
      short times and significantly slower at long times, can be explained using a
      model based on a two-stage chain formation and coarsening processes.

PMID- 19113132
TI  - Structural difference between liquidlike and gaslike phases in supercritical
      fluid.
AB  - Density fluctuation structures of supercritical carbon dioxide along the
      isothermal and isochoric lines were observed with small-angle neutron scattering
      (SANS). All the scattering intensities in the low-Q range were well described
      with the Ornstein-Zernike (OZ) equation. It was confirmed that there exists a
      locus where the OZ correlation length and scattering intensity at Q=0 exhibit
      extrema on the isothermal lines: this locus, named the ridge, was interpreted as
      the boundary by which the supercritical state is divided into liquidlike and
      gaslike phases. In order to clarify the difference of the fluctuation structure
      between the liquidlike and the gaslike phases, a real-space molecular
      distribution was obtained with a reverse Monte Carlo (RMC) method. Number density
      distributions of CO2 molecules at all measured states were calculated with the
      real-space molecular distributions obtained. In addition, the statistical
      parameters of the number density distributions, the standard deviations, and the
      skewnesses, were examined. The standard deviations of the number density
      distributions almost coincide with the results of the OZ analysis. On the other
      hand, the skewnesses, which describe the asymmetric nature of the number density
      distribution, clearly showed a difference between the two phases: the skewness
      became negative in the liquidlike phase, positive in the gaslike phase, and
      almost zero at the nearest state to the ridge in all isotherms. It was proved
      with simple equations of statistical mechanics that the skewness is described as
      the first differential of the magnitude of the density fluctuation with respect
      to the pressure. We conclude that the skewness, obtained with a RMC analysis for
      SANS data, is an important structural parameter distinguishing between the
      liquidlike and gaslike phases.

PMID- 19113133
TI  - Viscous shear banding in foam.
AB  - Shear banding is an important feature of flow in complex fluids. Essentially,
      shear bands refer to the coexistence of flowing and nonflowing regions in driven
      material. Understanding the possible sources of shear banding has important
      implications for a wide range of flow applications. In this regard, quasi-two
      dimensional flow offers a unique opportunity to study competing factors that
      result in shear bands. One proposal for interpretation and analysis is the
      competition between intrinsic dissipation and an external source of dissipation.
      In this paper, we report on the experimental observation of the transition
      between different classes of shear bands that have been predicted to exist in
      cylindrical geometry as the result of this competition [R. J. Clancy, E. Janiaud,
      D. Weaire, and S. Hutzlet, Eur. J. Phys. E 21, 123 (2006)].

PMID- 19113134
TI  - Temperature dependence of the free volume from positron lifetime experiments and
      its relation to structural dynamics: phenylphthalein-dimethylether.
AB  - Positron annihilation lifetime spectroscopy (PALS) was used to study the
      microstructure of the free volume in the temperature range between 103 K and 393
      K in phenylphthalein-dimethylether (PDE), a low-molecular-weight glass former.
      Using the routine LIFETIME9.0, the ortho-positronium (o-Ps) lifetime distribution
      was analyzed, and from this, the volume distribution gn(vh) of subnanometer-size
      holes was calculated. From a comparison of PALS and specific volume data, the
      number density and the volume fraction of holes were estimated. These free-volume
      data, as a function of temperature, were used to test the validity of the Cohen
      Turnbull (CT) free-volume theory. It was found that the structural relaxation
      from dielectric spectroscopy can be described by the CT theory after introducing
      a corrected free volume (Vf-DeltaV), where DeltaV=0.014 cm3/g. The extended free
      volume theory of Cohen and Grest can be fitted to the dielectric-relaxation and
      free-volume data, but the parameters of both fits are not consistent. PDE shows
      some peculiar features. The "knee" in the o -Ps lifetime expansion and crossover
      in temperature dependence of the frequency of the primary dielectric relaxation
      process occur at different temperatures. In addition, the change in the Vogel
      Fulcher-Tammann parameters at TB/Tg=1.1 has no observable effect on the mean free
      volume vh (or Vf). The size of the smallest representative freely fluctuating
      subsystem, VSV estimated from the standard deviation sigmah of gn(vh), decreases
      from 4.1 nm3 to 2.6 nm3 when the temperature increases from T/Tg=1.0 to 1.15.
      Correspondingly, the length of dynamic heterogeneity, xi=VVS1/3, decreases from
      1.6 nm to 1.4 nm. It is concluded that at T/Tg approximately 1.10=TB/Tg the
      system transforms from a heterogeneous to a homogeneous (true) liquid.

PMID- 19113135
TI  - Liquid surface model for carbon nanotube energetics.
AB  - In the present paper we developed a model for calculating the energy of single
      wall carbon nanotubes of arbitrary chirality. This model, which we call as the
      liquid surface model, predicts the energy of a nanotube with relative error less
      than 1% once its chirality and the total number of atoms are known. The
      parameters of the liquid surface model and its potential applications are
      discussed. The model has been suggested for open end and capped nanotubes. The
      influence of the catalytic nanoparticle, atop which nanotubes grow, on the
      nanotube stability is also discussed. The suggested model gives an important
      insight in the energetics and stability of nanotubes of different chirality and
      might be important for the understanding of nanotube growth process. For the
      computations we use empirical Brenner and Tersoff potentials and discuss their
      applicability to the study of carbon nanotubes. From the calculated energies we
      determine the elastic properties of the single-wall carbon nanotubes (Young
      modulus, curvature constant) and perform a comparison with available experimental
      measurements and earlier theoretical predictions.

PMID- 19113136
TI  - Interplay between coarsening and nucleation in an Ising model with dipolar
      interactions.
AB  - We study the dynamical behavior of a square lattice Ising model with exchange and
      dipolar interactions by means of Monte Carlo simulations. After a sudden quench
      to low temperatures, we find that the system may undergo a coarsening process
      where stripe phases with different orientations compete, or alternatively it can
      relax initially to a metastable nematic phase and then decay to the equilibrium
      stripe phase through nucleation. We measure the distribution of equilibration
      times for both processes and compute their relative probability of occurrence as
      a function of temperature and system size. This peculiar relaxation mechanism is
      due to the strong metastability of the nematic phase, which goes deep into the
      low-temperature stripe phase. We also measure quasiequilibrium autocorrelations
      in a wide range of temperatures. They show a distinct decay to a plateau that we
      identify as due to a finite fraction of frozen spins in the nematic phase. We
      find indications that the plateau is a finite-size effect. Relaxation times as a
      function of temperature in the metastable region show super-Arrhenius behavior,
      suggesting a possible glassy behavior of the system at low temperatures.

PMID- 19113137
TI  - Phase behavior and molecular mobility of n-octylcyanobiphenyl confined to
      molecular sieves: dependence on the pore size.
AB  - The molecular dynamics of 4-n-octyl-4'-cyanobiphenyl (8CB) confined inside the
      pores of a series of AlMCM-41 samples with the same structure, constant
      composition (SiAl=14.7) but different pore sizes (diameter between 2.3 and 4.6
      nm) was investigated by broadband dielectric spectroscopy (10(-2)-10(9) Hz) in a
      large temperature interval. Two relaxation processes are observed: one has a
      bulklike behavior and is assigned to the 8CB in the pore center. The relaxation
      time of the second relaxation process is essentially slower than that of the
      former one and this process is related to the dynamics of molecules in a surface
      layer with a paranematic order. Both relaxation processes are specifically
      influenced by the interaction of the molecules with the surface and by the
      confinement. Above the clearing temperature the temperature dependence of the
      relaxation rate of the bulklike process obeys the Vogel-Fulcher-Tammann (VFT)
      law. The Vogel temperature increases with decreasing pore size. This is explained
      by increasing influence of paranematic potential of the surface layer with
      decreasing pore size. The temperature dependence of the relaxation rate of the
      surface layer follows also the VFT formula and the Vogel temperature decreases
      with decreasing pore size. This temperature dependence is controlled by both the
      interaction of the 8CB molecules with the surface via hydrogen bonding and by
      spatial confinement effects. To discriminate between both effects the data for
      the surface layer of 8CB confined to the molecular sieves are compared with
      results concerning 8CB adsorbed as a quasimonolayer on the surface of silica
      spheres of aerosil. On this basis a confinement parameter is defined and
      discussed.

PMID- 19113138
TI  - Biaxial nematic order and phase behavior studies in an organosiloxane tetrapode
      using complementary deuterium NMR experiments.
AB  - The biaxial nematic phase was recently observed in different thermotropic liquid
      crystals, namely bent-core compounds, side-chain polymers, bent-core dimers, and
      organosiloxane tetrapodes. In this work, a series of experiments with a nematic
      organosiloxane tetrapode where nuclear magnetic resonance (NMR) spectra are
      collected while the sample is continuously rotating around an axis perpendicular
      to the magnetic field, are discussed in conjunction with the analysis of a
      deuterium NMR experiment on the same system reported earlier. The sample used is
      a mixture of a deuterated probe with the tetrapode. The mixture exhibits a
      nematic range between -40 degrees C and 37 degrees C. The results of the two
      independent, but complementary deuterium NMR experiments confirm the existence of
      a biaxial nematic phase for temperatures below 0 degrees C with high values of
      the asymmetry parameter at low temperatures. The presence of slow movements of
      the tetrapode mesogenic units in the low-temperature regime could also be
      detected through the analysis of the NMR spectra. Simulations indicate that these
      movements are mainly slow molecular reorientations of the mesogenic units
      associated with the presence of collective modes in the nematic phases of this
      compound. In the case of tetrapodes, recent investigations attribute the origin
      of biaxiality to the hindering of reorientations of the laterally attached
      mesogenic units which constitute the tetrapode. This study relates the molecular
      movements with the nematic biaxial ordering of the system.

PMID- 19113139
TI  - Landau model for polymer-stabilized ferroelectric liquid crystals: experiment and
      theory.
AB  - The interaction between a phase separated polymer network and a liquid crystal
      was studied across the smectic-A* (Sm-A*) to smectic-C* (Sm-C*) phase transition
      of a polymer-stabilized ferroelectric liquid crystal polymerized in the Sm-A*
      phase. Using precise measurements of the tilt angle and the spontaneous
      polarization as functions of the external electric field and polymer
      concentration, the effective coefficients of the Landau expansion of the free
      energy of the Sm-C* phase have been determined experimentally. The observed
      polymer concentration dependence of the Landau expansion coefficients is
      explained using a more general theoretical model which incorporates the effect of
      polymer networks on the local liquid crystal director configuration. In
      particular, using experimental estimates of the penetration depth of the polymer
      network into the liquid crystal, it is shown that the b coefficient calculated
      from the Landau model increases with polymer concentration, evidencing the
      relationship determined experimentally.

PMID- 19113140
TI  - Shear-induced domain deformation in a tilted lipid monolayer: from circle to
      ellipse and kinked stripe.
AB  - The shear-induced domain deformation in a lipid monolayer comprised of tilted
      molecules is studied as a mechanical balance between surface pressure, line
      tension, electrostatic energy due to the dipole-dipole interaction, hexatic
      elastic stress, and viscous stress. It is found that a simple shear can deform a
      circular domain into an elliptic shape with the long axis inclined 45 degrees
      from the shear direction. The "ellipse" is elongated in the long axis as shear
      rate increases, and evolves to a straight or kinked stripe, which was observed as
      a "shear band" by Fuller's group [Science 274, 233 (1996)] and "avalanche-like
      fronts" by Schwaltz's group [Langmuir 17, 3017 (2001)], at a threshold shear
      rate. The propagation of stripe-shaped domains is discussed in the context of
      electrostatic energy. The dependence of the threshold shear rate on surface
      pressure is predicted in good agreement with observation and can be used to
      estimate surface viscosity. The shear-induced domain deformation is maintained by
      the effect of the lattice elastic stress when shear ceases.

PMID- 19113141
TI  - Elastic constants of hard thin platelets by Monte Carlo simulation and virial
      expansion.
AB  - In this paper we present an investigation into the calculation of the Frank
      elastic constants of hard platelets via molecular simulation and virial expansion
      beyond second order. Monte Carlo simulations were carried out and director
      fluctuations measured as a function of wave vector k, giving the elastic
      constants through a fit in the low-k limit. Additionally, the virial expansion
      coefficients of the elastic constants up to sixth order were calculated, and the
      validity of the theory determined by comparison with the simulation results. The
      simulation results are also compared with experimental measurements on colloidal
      suspensions of platelike particles.

PMID- 19113142
TI  - No quasi-long-range order in a two-dimensional liquid crystal.
AB  - Systems with global symmetry group O(2) experience topological transition in the
      two-dimensional space. But there is controversy about such a transition for
      systems with global symmetry group O(3). As an example of the latter case, we
      study the Lebwohl-Lasher model for the two-dimensional liquid crystal, using
      three different methods independent of the proper values of possible critical
      exponents. Namely, we analyze the at-equilibrium order parameter distribution
      function with (1) the hyperscaling relation; (2) the first-scaling collapse for
      the probability distribution function; and (3) the Binder's cumulant. We give
      strong evidence for definite lack of a line of critical points at low
      temperatures in the Lebwohl-Lasher model, contrary to conclusions of a number of
      previous numerical studies.

PMID- 19113143
TI  - Monte Carlo study of multiply crosslinked semiflexible polymer networks.
AB  - We present a method to generate realistic, three-dimensional networks of
      crosslinked semiflexible polymers. The free energy of these networks is obtained
      from the force-extension characteristics of the individual polymers and their
      persistent directionality through the crosslinks. A Monte Carlo scheme is
      employed to obtain isotropic, homogeneous networks that minimize the free energy
      and for which all of the relevant parameters can be varied: the persistence
      length and the contour length as well as the crosslinking length may be chosen at
      will. We also provide an initial survey of the mechanical properties of our
      networks subjected to shear strains, showing them to display the expected
      nonlinear stiffening behavior. Also, a key role for nonaffinity and its relation
      to order in the network is uncovered.

PMID- 19113144
TI  - Mechanical properties of an adsorbed elastic polymer in contact with a rigid
      membrane.
AB  - A static and a dynamical model are introduced to study the physical properties of
      an elastic polymer adsorbed on a rigid membrane. We analyze the detailed
      microscopic model for the adhesion problem and show that in the force ensemble a
      critical force is expected. Forces smaller than the critical value are not able
      to peel off the filament, while larger forces will cause the filament to
      completely desorb from the membrane. To demonstrate the nonequilibrium properties
      of the moving states for forces larger than the critical value, we present the
      linear response of the system in the form of a force-velocity relation. In
      addition, we use a very simple short-range static model and obtain the
      equilibrium phases of the system in different cases where either a fixed force or
      a fixed height can be applied at the end. For the fixed force the equilibrium
      phases arising from the static model are in agreement with dynamical model.
      Forces smaller than the critical value are not able to peel off the filament
      while the larger forces will cause the filament to completely desorb as in the
      dynamical model.

PMID- 19113145
TI  - Effect of excluded volume on segmental orientation correlations in polymer
      chains.
AB  - We study the impact of excluded volume interactions on the orientation statistics
      of chain segments in polymer gels, and show that nuclear magnetic resonance (NMR)
      experiments provide a direct and unique measure of excluded-volume effects on the
      chain statistics. In particular we consider the tensor order parameter, which can
      be expressed as the second Legendre polynomial of the segment orientation with
      respect to a fixed end-to-end distance vector and which is directly related to
      the residual coupling constant obtained in NMR experiments. We provide analytical
      results for the case of single chains in a good solvent and for semidilute
      solutions. Computer simulations using the bond fluctuation model are applied to
      compare with the analytical predictions. Considering polymer gels at the
      equilibrium state of swelling we predict a unique relation between the tensor
      order parameter and the correlation length (blob size) of the gel. Experiments
      applying multiple-quantum NMR methods to both end-linked and randomly cross
      linked polymer networks are in excellent agreement with this prediction. The
      initial decay of the tensor order parameter as observed in experiments at low and
      intermediate degrees of swelling can be explained as a solvent effect without
      making additional assumptions about constraint release processes during swelling.

PMID- 19113146
TI  - Equilibrium characteristics of semiflexible polymer solutions near probe
      particles.
AB  - We present a numerical analysis of the mean-field theory for the structure of
      semiflexible polymer solutions near spherical surfaces, and use the framework to
      study the depletion characteristics of semiflexible polymers near colloids and
      nanoparticles. Our results suggest that the depletion characteristics depend
      sensitively on the polymer concentrations, the persistence lengths, and the
      radius of the particles. Broadly, two categories of features are identified based
      on the relative ratios of the persistence lengths to the correlation length of
      the polymer solution. For the limit where the correlation length is larger than
      the persistence length, the correlation length proves to be the critical length
      scale governing both the depletion thickness and the curvature effects. In
      contrast, for the opposite limit, the depletion thickness and the curvature
      effects are dependent on a length scale determined by an interplay between the
      persistence length and the correlation length. This leads to nontrivial
      (numerical) scaling laws governing the concentration and radii dependence of the
      depletion thicknesses. Our study also highlights the manner by which the
      preceding features rationalize the parametric dependencies of insertion free
      energies of small probes in semiflexible polymer solutions.

PMID- 19113147
TI  - Dynamics of a single polymer chain: ergodicity and conformation of a rotating
      chain.
AB  - The dynamics of an isolated polymer chain has irreversible aspects that lead to
      the decorrelation of configurational properties over time. For simple mechanical
      models with time reversible equations of motion, the irreversibility is a
      consequence of the chaotic nature of the dynamics which, for a many body system,
      is expected to result in ergodic mixing. Here we study a fixed bond length N-mer
      interaction-site chain with fixed total energy and angular momentum. For N>or=4
      the equations of motion for such a chain are nonintegrable and chaotic dynamics
      is expected. We directly assess the ergodicity of short repulsive Lennard-Jones
      chains by comparing phase space and time averages for structural and energetic
      properties. The phase space averages are determined from the exact microcanonical
      partition function while the time averages are obtained from molecular dynamics
      (MD) simulations. For N=4 and 5 we find that our exact phase space averages agree
      with the MD time averages, as expected for an ergodic system. The N=3 system is
      integrable and thus displays regular dynamics for which time averages are found
      to depend on initial conditions. In all cases, the total angular momentum is
      found to have a large effect on both the average chain conformation and the
      partitioning of the total energy between potential, vibrational, and rotational
      contributions. Compared to a nonrotating chain, a small to moderate angular
      momentum slightly speeds up the internal chain dynamics, while a large angular
      momentum dramatically slows the internal dynamics.

PMID- 19113148
TI  - Polymer deformation in Brownian ratchets: theory and molecular dynamics
      simulations.
AB  - We examine polymers in the presence of an applied asymmetric sawtooth (ratchet)
      potential which is periodically switched on and off, using molecular dynamics
      (MD) simulations with an explicit Lennard-Jones solvent. We show that the
      distribution of the center of mass for a polymer in a ratchet is relatively wide
      for potential well depths U0 on the order of several kBT. The application of the
      ratchet potential also deforms the polymer chains. With increasing U0 the Flory
      exponent varies from that for a free three-dimensional (3D) chain, nu=35 (U0=0),
      to that corresponding to a 2D compressed (pancake-shaped) polymer with a value of
      nu=34 for moderate U0. This has the added effect of decreasing a polymer's
      diffusion coefficient from its 3D value D3D to that of a pancaked-shaped polymer
      moving parallel to its minor axis D2D. The result is that a polymer then has a
      time-dependent diffusion coefficient D(t) during the ratchet off time. We further
      show that this suggests a different method to operate a ratchet, where the off
      time of the ratchet, toff, is defined in terms of the relaxation time of the
      polymer, tauR. We also derive a modified version of the Bader ratchet model
      [Bader, Proc. Natl. Acad. Sci. U.S.A. 96, 13165 (1999)] which accounts for this
      deformation and we present a simple expression to describe the time dependent
      diffusion coefficient D(t). Using this model we then illustrate that polymer
      deformation can be used to modulate polymer migration in a ratchet potential.

PMID- 19113149
TI  - Modeling distributed axonal delays in mean-field brain dynamics.
AB  - The range of conduction delays between connected neuronal populations is often
      modeled as a single discrete delay, assumed to be an effective value averaging
      over all fiber velocities. This paper shows the effects of distributed delays on
      signal propagation. A distribution acts as a linear filter, imposing an upper
      frequency cutoff that is inversely proportional to the delay width. Distributed
      thalamocortical and corticothalamic delays are incorporated into a
      physiologically based mean-field model of the cortex and thalamus to illustrate
      their effects on the electroencephalogram (EEG). The power spectrum is acutely
      sensitive to the width of the thalamocortical delay distribution, and more so
      than the corticothalamic distribution, because all input signals must travel
      along the thalamocortical pathway. This imposes a cutoff frequency above which
      the spectrum is overly damped. The positions of spectral peaks in the resting EEG
      depend primarily on the distribution mean, with only weak dependences on
      distribution width. Increasing distribution width increases the stability of
      fixed point solutions. A single discrete delay successfully approximates a
      distribution for frequencies below a cutoff that is inversely proportional to the
      delay width, provided that other model parameters are moderately adjusted. A pair
      of discrete delays together having the same mean, variance, and skewness as the
      distribution approximates the distribution over the same frequency range without
      needing parameter adjustment. Delay distributions with large fractional widths
      are well approximated by low-order differential equations.

PMID- 19113150
TI  - Nanomorphology of the blue iridescent wings of a giant tropical wasp Megascolia
      procer javanensis (Hymenoptera).
AB  - The wings of the giant wasp Megascolia procer javanensis are opaque and
      iridescent. The origin of the blue-green iridescence is studied in detail, using
      reflection spectroscopy, scanning electron microscopy, and physical modeling. It
      is shown that the structure responsible for the iridescence is a single
      homogeneous transparent chitin layer covering the whole surface of each wing. The
      opacity is essentially due to the presence of melanin in the stratified medium
      which forms the mechanical core of the wing.

PMID- 19113151
TI  - Model of human immunodeficiency virus budding and self-assembly: role of the cell
      membrane.
AB  - Budding from the plasma membrane of the host cell is an indispensable step in the
      life cycle of the human immunodeficiency virus (HIV), which belongs to a large
      family of enveloped RNA viruses, retroviruses. Unlike regular enveloped viruses,
      retrovirus budding happens concurrently with the self-assembly of the main
      retrovirus protein subunits (called Gag protein after the name of the genetic
      material that codes for this protein: Group-specific AntiGen) into spherical
      virus capsids on the cell membrane. Led by this unique budding and assembly
      mechanism, we study the free energy profile of retrovirus budding, taking into
      account the Gag-Gag attraction energy and the membrane elastic energy. We find
      that if the Gag-Gag attraction is strong, budding always proceeds to completion.
      During early stage of budding, the zenith angle of partial budded capsids, alpha
      , increases with time as alpha proportional t1/2. However, if the Gag-Gag
      attraction is weak, a metastable state of partial budding appears. The zenith
      angle of these partially spherical capsids is given by alpha0 approximately
      (tau2/kappasigma)1/4 in a linear approximation, where kappa and sigma are the
      bending modulus and the surface tension of the membrane, and tau is a line
      tension of the capsid proportional to the strength of Gag-Gag attraction.
      Numerically, we find alpha0<0.3pi without any approximations. Using experimental
      parameters, we show that HIV budding and assembly always proceed to completion in
      normal biological conditions. On the other hand, by changing Gag-Gag interaction
      strength or membrane rigidity, it is relatively easy to tune it back and forth
      between complete budding and partial budding. Our model agrees reasonably well
      with experiments observing partial budding of retroviruses including HIV.

PMID- 19113152
TI  - Statistical mechanical model for helix-sheet-coil transitions in
      homopolypeptides.
AB  - In this paper, we propose a simple statistical mechanical model to study the
      conformation transition between the alpha helix, beta sheet, and random coil in
      homopolypeptides. In our model, five parameters are introduced to obtain the
      partition function. There are two factors for helical propagation and initiation,
      which are the same as those used in the Zimm-Bragg model, and three newly
      introduced parameters for beta structures: the strand propagation factor for
      residues in beta strands and two correction factors for the initiation effect of
      the beta strand and beta sheet. Our model shows that the variation of these
      parameters may induce conformation transition from alpha helix or random coil to
      beta sheet. The sharpness of the transition depends on the initiation factors.

PMID- 19113153
TI  - Polarizability of shelled particles of arbitrary shape in lossy media with an
      application to hematic cells.
AB  - We show that within the dipole approximation the complex polarizability of
      shelled particles of arbitrary shape can be written as the volume of the particle
      times a weighted average of the electric field in the particle, with weights
      determined by the differences in permittivities between the shells and the
      external, possibly lossy media. To calculate the electric field we use an
      adaptive-mesh finite-element method which is very effective in handling the
      irregular domains, material inhomogeneities, and complex boundary conditions
      usually found in biophysical applications. After extensive tests with exactly
      solvable models, we apply the method to four types of hematic cells: platelets, T
      lymphocytes, erythrocytes, and stomatocytes. Realistic shapes of erythrocytes and
      stomatocytes are generated by a parametrization in terms of Jacobi elliptic
      functions. Our results show, for example, that if the average polarizability is
      the main concern, a confocal ellipsoid may be used as a model for a normal
      erythrocyte, but not for a stomatocyte. A comparison with experimental
      electrorotation data shows quantitatively the effect of an accurate geometry in
      the derivation of electrical cell parameters from fittings of theoretical models
      to the experimental data.

PMID- 19113154
TI  - Adsorption-induced vesicle fission.
AB  - A theoretical model for vesicle fission induced by particle adsorption and
      aggregation on a membrane surface is presented. The bulk fluid contains particles
      that are adsorbed reversibly to the membrane. Adsorbed particles aggregate on the
      membrane, forming particle-rich domains. Domains at a critical size which
      contains nv particles become vesicles and leave the membrane. We find that for
      parameters that correspond to typical experimental situations, vesicle formation
      is energetically favored except for a possible energy barrier for domain
      nucleation at small n, where n is the number of particles in a domain. We also
      find that in typical experimental situations a particle-rich domain grows without
      being affected strongly by neighboring domains, and the vesicle formation rate is
      proportional to adsorption rate jon when jon is large; when jon is small the
      vesicle formation rate scales like jon2. Because the diffusion flux is small for
      domains with small in-plane radius Rn, in the time-independent state the
      densities of domains with n/nv<<1 and 1-n/nv<<1 are large.

PMID- 19113155
TI  - Estimating the phase of synchronized oscillators.
AB  - The state of a collection of phase-locked oscillators is determined by a single
      phase variable or cyclic coordinate. This paper presents a computational method,
      Phaser, for estimating the phase of phase-locked oscillators from limited amounts
      of multivariate data in the presence of noise and measurement errors.
      Measurements are assumed to be a collection of multidimensional time series. Each
      series consists of several cycles of the same or similar systems. The oscillators
      within each system are not assumed to be identical. Using measurements of the
      noise covariance for the multivariate input, data from the individual oscillators
      in the system are combined to reduce the variance of phase estimates for the
      whole system. The efficacy of the algorithm is demonstrated on experimental and
      model data from biomechanics of cockroach running and on simulated oscillators
      with varying levels of noise.

PMID- 19113156
TI  - Conformational transformations induced by the charge-curvature interaction at
      finite temperature.
AB  - The role of thermal fluctuations in the conformational dynamics of a single
      closed filament is studied. It is shown that, due to the interaction between
      charges and bending degrees of freedom, initially circular aggregates may undergo
      transformation to a polygonal shape. The transition occurs in the cases of
      hardening and softening charge-bending interaction. In the former case the charge
      and curvature are smoothly distributed along the chain, while in the latter
      spontaneous kink formation is initiated. The transition to a noncircular
      conformation is analogous to a phase transition of the second kind.

PMID- 19113158
TI  - Melting of persistent double-stranded polymers.
AB  - Motivated by recent DNA-pulling experiments, we revisit the Poland-Scheraga model
      of melting a double-stranded polymer. We include distinct bending rigidities for
      both the double-stranded segments and the single-stranded segments forming a
      bubble. There is also bending stiffness at the branch points between the two
      segment types. The transfer matrix technique for single persistent chains is
      generalized to describe the branching bubbles. Properties of spherical harmonics
      are then exploited in truncating and numerically solving the resulting transfer
      matrix. This allows efficient computation of phase diagrams and force-extension
      curves (isotherms). While the main focus is on exposition of the transfer matrix
      technique, we provide general arguments for a reentrant melting transition in
      stiff double strands. Our theoretical approach can also be extended to study
      polymers with bubbles of any number of strands, with potential applications to
      molecules such as collagen.

PMID- 19113157
TI  - Detection of subthreshold pulses in neurons with channel noise.
AB  - Neurons are subject to various kinds of noise. In addition to synaptic noise, the
      stochastic opening and closing of ion channels represents an intrinsic source of
      noise that affects the signal-processing properties of the neuron. We study the
      response of a stochastic Hodgkin-Huxley neuron to transient input subthreshold
      pulses. It is found that the average response time decreases but variance
      increases as the amplitude of channel noise increases. In the case of single
      pulse detection, we show that channel noise enables one neuron to detect the
      subthreshold signals and an optimal membrane area (or channel noise intensity)
      exists for a single neuron to achieve optimal performance. However, the detection
      ability of a single neuron is limited by large errors. Here, we test a simple
      neuronal network that can enhance the pulse-detecting abilities of neurons and
      find that dozens of neurons can perfectly detect subthreshold pulses. The
      phenomenon of intrinsic stochastic resonance is also found at both the level of
      single neurons and the level of networks. At the network level, the detection
      ability of networks can be optimized for the number of neurons comprising the
      network.

PMID- 19113159
TI  - Quasicycles in a spatial predator-prey model.
AB  - We use spatial models of simple predator-prey interactions to predict that
      predator and prey numbers oscillate in time and space. These oscillations are not
      seen in the deterministic versions of the models, but are due to stochastic
      fluctuations about the time-independent solutions of the deterministic equations
      which are amplified due to the existence of a resonance. We calculate the power
      spectra of the fluctuations analytically and show that they agree well with
      results obtained from stochastic simulations. This work extends the analysis of
      these quasicycles from that previously developed for well-mixed systems to
      spatial systems, and shows that the ideas and methods used for nonspatial models
      naturally generalize to the spatial case.

PMID- 19113160
TI  - Active transport on disordered microtubule networks: the generalized random
      velocity model.
AB  - The motion of small cargo particles on microtubules by means of motor proteins in
      disordered microtubule networks is investigated theoretically using both
      analytical tools and computer simulations. Different network topologies in two
      and three dimensions are considered, one of which has been recently studied
      experimentally by Salman [Biophys. J. 89, 2134 (2005)]. A generalization of the
      random velocity model is used to derive the mean-square displacement of the cargo
      particle. We find that all cases belong to the class of anomalous superdiffusion,
      which is sensitive mainly to the dimensionality of the network and only
      marginally to its topology. Yet in three dimensions the motion is very close to
      simple diffusion, with sublogarithmic corrections that depend on the network
      topology. When details of the thermal diffusion in the bulk solution are
      included, no significant change to the asymptotic time behavior is found.
      However, a small asymmetry in the mean microtubule polarity affects the
      corresponding long-time behavior. We also study a three-dimensional model of the
      microtubule network in living animal cells. Three first-passage-time problems of
      intracellular transport are simulated and analyzed for different motor
      processivities: (i) cargo that originates near the nucleus and has to reach the
      membrane, (ii) cargo that originates from the membrane and has to reach the
      nucleus, and (iii) cargo that leaves the nucleus and has to reach a specific
      target in the cytoplasm. We conclude that while a higher motor processivity
      increases the transport efficiency in cases (i) and (ii), in case (iii) it has
      the opposite effect. We conjecture that the balance between the different network
      tasks, as manifested in cases (i) and (ii) versus case (iii), may be the reason
      for the evolutionary choice of a finite motor processivity.

PMID- 19113161
TI  - Calculating free-energy profiles in biomolecular systems from fast nonequilibrium
      processes.
AB  - Often gaining insight into the functioning of biomolecular systems requires to
      follow their dynamics along a microscopic reaction coordinate (RC) on a
      macroscopic time scale, which is beyond the reach of current all atom molecular
      dynamics (MD) simulations. A practical approach to this inherently multiscale
      problem is to model the system as a fictitious overdamped Brownian particle that
      diffuses along the RC in the presence of an effective potential of mean force
      (PMF) due to the rest of the system. By employing the recently proposed FR method
      [I. Kosztin, J. Chem. Phys. 124, 064106 (2006)], which requires only a small
      number of fast nonequilibrium MD simulations of the system in both forward and
      time reversed directions along the RC, we reconstruct the PMF: (1) of deca
      alanine as a function of its end-to-end distance, and (2) that guides the motion
      of potassium ions through the gramicidin A channel. In both cases the computed
      PMFs are found to be in good agreement with previous results obtained by
      different methods. Our approach appears to be about one order of magnitude faster
      than the other PMF calculation methods and, in addition, it also provides the
      position-dependent diffusion coefficient along the RC. Thus, the obtained PMF and
      diffusion coefficient can be used in an overdamped Brownian model to estimate
      important characteristics of the studied systems, e.g., the mean folding time of
      the stretched deca-alanine and the mean diffusion time of the potassium ion
      through gramicidin A.

PMID- 19113162
TI  - Intrinsic inhomogeneities and the coexistence of spirals with different periods
      of rotation.
AB  - We propose a mechanism by which wave fronts emanating from a spiral may break far
      from the spiral core due to intrinsic spatial inhomogeneities. A series of
      computer simulations are presented to demonstrate how coupling domains, which on
      their own would not cause breakup, may cause a single spiral to break into many
      spirals.

PMID- 19113163
TI  - Nonspecific interactions in spontaneous assembly of empty versus functional
      single-stranded RNA viruses.
AB  - We investigate the influence of salt concentration, charge on viral proteins and
      the length of single-stranded RNA (ssRNA) molecule on the spontaneous assembly of
      viruses. Only the nonspecific interactions are assumed to guide the assembly,
      i.e., we exclude any chemical specificity that may lock the viral proteins and
      ssRNA in preferred configurations. We demonstrate that the electrostatic
      interactions screened by the salt in the solution impose strong limits on viral
      composition that can be achieved by spontaneous assembly. In particular, we show
      that viruses whose ssRNA carries more than twice the amount of charge that is
      located on the viral proteins, cannot be assembled spontaneously. We find that
      the spatial distribution of protein charge is important for the energetics of the
      assembly. We also show that the pressures that act on the viruses as a result of
      attractive protein-ssRNA electrostatic interactions are at least an order of
      magnitude smaller than is the case with bacteriophage viruses that contain double
      stranded DNA molecule.

PMID- 19113164
TI  - Photodissociation pathways of gas-phase photoactive yellow protein chromophores.
AB  - The absorption dynamics of two model chromophores of the photoactive yellow
      protein were studied in gas-phase experiments. Using different time-resolving
      techniques with an overall sensitivity ranging from seconds down to a few
      nanoseconds, complex dynamics were revealed for the p -coumaric acid anion,
      involving both fragmentation and electron detachment as possible photoresponse
      channels. For the trans-thiophenyl-p-coumarate model, despite its more complex
      molecular structure, simpler decay dynamics showing only fragmentation were
      observed.

PMID- 19113165
TI  - Active paradigms of seizure anticipation: computer model evidence for necessity
      of stimulation.
AB  - It has been shown that the analysis of electroencephalographic (EEG) signals
      submitted to an appropriate external stimulation (active paradigm) is efficient
      with respect to anticipating epileptic seizures [S. Kalitzin, Clin. Neurophysiol.
      116, 718 (2005)]. To better understand how an active paradigm is able to detect
      properties of EEG signals by means of which proictal states can be identified, we
      performed a simulation study using a computational model of seizure generation of
      a hippocampal network. Applying the active stimulation methodology, we
      investigated (i) how changes in model parameters that lead to a transition from
      the normal ongoing EEG to an ictal pattern are reflected in the properties of the
      simulated EEG output signals and (ii) how the evolution of neuronal excitability
      towards seizures can be reconstructed from EEG data using an active paradigm,
      rather than passively, using only ongoing EEG signals. The simulations indicate
      that a stimulation paradigm combined with appropriate analytical tools, as
      proposed here, may yield information about the change in excitability that
      precedes the transition to a seizure. Such information is apparently not fully
      reflected in the ongoing EEG activity. These findings give strong support to the
      development and application of active paradigms with the aim of predicting the
      occurrence of a transition to an epileptic seizure.

PMID- 19113166
TI  - Strong short-range correlations and dichotomic codon classes in coding DNA
      sequences.
AB  - The study of correlation structures in DNA sequences is of great interest because
      it allows us to obtain structural and functional information about underlying
      genetic mechanisms. In this paper we present a study of the correlation structure
      of protein coding sequences of DNA based on a recently developed mathematical
      representation of the genetic code. A fundamental consequence of such
      representation is that codons can be assigned a parity class (odd-even). Such
      parity can be obtained by means of a nonlinear algorithm acting on the chemical
      character of the codon bases. In the same setting the Rumer's class can be
      naturally described and a new dichotomic class, the hidden class, can be defined.
      Moreover, we show that the set of DNA's base transformations associated to the
      three dichotomic classes can be put in a compact group-theoretic framework. We
      use the dichotomic classes as a coding scheme for DNA sequences and study the
      mutual dependence between such classes. The same analysis is carried out also on
      the chemical dichotomies of DNA bases. In both cases, the statistical analysis is
      performed by using an entropy-based dependence metric possessing many desirable
      properties. We obtain meaningful tests for mutual dependence by using suitable
      resampling techniques. We find strong short-range correlations between certain
      combinations of dichotomic codon classes. These results support our previous
      hypothesis that codon classes might play an active role in the organization of
      genetic information.

PMID- 19113167
TI  - Membrane fluctuations near a plane rigid surface.
AB  - We use analytical calculations and Monte Carlo simulations to determine the
      thermal fluctuation spectrum of a membrane patch of a few tens of nanometer in
      size, whose corners are located at a fixed distance d above a plane rigid
      surface. Our analysis shows that the surface influence on the bilayer
      fluctuations can be effectively described in terms of a uniform confining
      potential that grows quadratically with the height of the membrane h relative to
      the surface: V=(1/2)gammah2. The strength gamma of the harmonic confining
      potential vanishes when the corners of the membrane patch are placed directly on
      the surface (d=0), and achieves its maximum value when d is of the order of a few
      nanometers. However, even at maximum strength, the confinement effect is quite
      small and has a noticeable impact only on the amplitude of the largest bending
      mode.

PMID- 19113168
TI  - Modeling the impact of impulsive stimuli on sleep-wake dynamics.
AB  - A neuronal population model of the sleep-wake switch is extended to incorporate
      impulsive external stimuli. The model includes the mutual inhibition of the sleep
      active neurons in the hypothalamic ventrolateral preoptic area (VLPO) and the
      wake-active monoaminergic brainstem populations (MA), as well as circadian and
      homeostatic drives. Arbitrary stimuli are described in terms of their relative
      effects on the VLPO and MA nuclei and represent perturbations on the normal sleep
      wake dynamics. By separating the model's intrinsic time scales, an analytic
      characterization of the dynamics in a reduced model space is developed. Using
      this representation, the model's response to stimuli is studied, including the
      latency to return to wake or sleep, or to elicit a transition between the two
      states. Since sensory stimuli are known to excite the MA, we correspondingly
      investigate the model's response to auditory tones during sleep, as in clinical
      sleep fragmentation studies. The arousal threshold is found to vary approximately
      linearly with the model's total sleep drive, which includes circadian and
      homeostatic components. This relationship is used to reproduce the clinically
      observed variation of the arousal threshold across the night, which rises to a
      maximum near the middle of the night and decreases thereafter. In a further
      application of the model, time-of-night arousal threshold and body temperature
      variations in an experimental sleep fragmentation study are replicated. It is
      proposed that the shift of the extrema of these curves to a greater magnitude
      later in the night is due to the homeostatic impact of the frequent nocturnal
      disturbances. By modeling the underlying neuronal interactions, the methods
      presented here allow the prediction of arousal state responses to external
      stimuli. This methodology is fundamentally different to previous approaches that
      model the clinical data within a phenomenological framework. As a result, a
      broader understanding of how impulsive external stimuli modulate arousal is
      gained.

PMID- 19113169
TI  - Three-state kinetic mechanism for scaffold-mediated signal transduction.
AB  - Signaling events in eukaryotic cells are often guided by a scaffolding protein.
      Scaffold proteins assemble multiple proteins into a spatially localized signaling
      complex and exert numerous physical effects on signaling pathways. To study these
      effects, we consider a minimal, three-state kinetic model of scaffold-mediated
      kinase activation. We first introduce and apply a path summation technique to
      obtain approximate solutions to a single molecule master equation that governs
      protein kinase activation. We then consider exact numerical solutions. We comment
      on when this approximation is appropriate and then use this analysis to
      illustrate the competition of processes occurring at many time scales that are
      involved in signal transduction in the presence of a scaffold protein. We find
      that our minimal model captures how scaffold concentration can influence the
      times over which signaling is distributed in kinase cascades. For a range of
      scaffold concentrations, scaffolds allow for signaling to be distributed over
      multiple decades. The findings are consistent with recent experiments and
      simulation data. These results provide a framework and offer a mechanism for
      understanding how scaffold proteins can influence the shape of the waiting time
      distribution of kinase activation and effectively broaden the times over which
      protein kinases are activated in the course of cell signaling.

PMID- 19113170
TI  - Spontaneous firing statistics and information transfer in electroreceptors of
      paddlefish.
AB  - We study information processing in a peripheral sensory receptor system which
      possesses spontaneous dynamics with two distinct rhythms. Such organization was
      found in the electrosensory system of paddlefish and is represented by two
      distinct and unidirectionally coupled oscillators, resulting in biperiodic
      spontaneous firing patterns of sensory neurons. We use computational modeling to
      elucidate the functional role of spontaneous oscillations in conveying
      information from sensory periphery to the brain. We show that biperiodic
      organization resulting in nonrenewal statistics of background neuronal activity
      leads to significant improvement in information transfer through the system as
      compared to an equivalent renewal model.

PMID- 19113171
TI  - Consensus of population systems with community structures.
AB  - Multicommunity population systems may reach a consensus state where the fractions
      of each species in different communities agree on a common value. In this paper,
      by analyzing the evolutionary dynamics based on an extended replicator equation
      incorporating community effects, the consensus problem of population systems with
      n communities is studied. In particular, the simple case of two communities is
      investigated in detail. In general, for n communities, a sufficient and necessary
      condition for population systems to reach a consensus of coexistent state is
      provided. Regarding the population dynamics for the four different types of
      games, whether the population systems can achieve consensus is determined. The
      dynamics of community-structured populations shows richer features than
      nonstructured populations, and some nontrivial phenomena arising from different
      community-structured population systems are illustrated with concrete numerical
      examples.

PMID- 19113172
TI  - Elastic properties and mechanical stability of chiral and filled viral capsids.
AB  - The elasticity and mechanical stability of empty and filled viral capsids under
      external force loading are studied in a combined analytical and numerical
      approach. We analyze the influence of capsid structure and chirality on the
      mechanical properties. We find that generally skew shells have lower stretching
      energy. For large Foppl-von Karman numbers gamma (gamma approximately 10(5)),
      skew structures are stiffer in their elastic response than nonchiral ones. The
      discrete structure of the capsules not only leads to buckling for large gamma but
      also influences the breakage behavior of capsules below the buckling threshold:
      the rupture force shows a gamma1/4 scaling rather than a gamma1/2 scaling as
      expected from our analytical results for continuous shells. Filled viral capsids
      are exposed to internal anisotropic pressure distributions arising from regularly
      packaged DNA coils. We analyze their influence on the elastic properties and
      rupture behavior and we discuss possible experimental consequences. Finally, we
      numerically investigate specific sets of parameters corresponding to specific
      phages such as phi29 and cowpea chlorotic mottle virus (CCMV). From the
      experimentally measured spring constants we make predictions about specific
      material parameters (such as bending rigidity and Young's modulus) for both empty
      and filled capsids.

PMID- 19113173
TI  - Mean first-passage time for superdiffusion in a slit pore with sticky boundaries.
AB  - This Brief Report examines Levy motion in a slit pore with sticky boundaries,
      i.e., boundaries that absorb particles for a random amount of time. A set of
      equations is developed that can explicitly be solved for mean travel distance to
      a plane for a particle released from the origin and can iteratively be used to
      compute mean first-passage time (MFPT). Results from the theory compare favorably
      with Monte Carlo simulations.

PMID- 19113174
TI  - Langevin dynamics in crossed magnetic and electric fields: Hall and diamagnetic
      fluctuations.
AB  - Based on the classical Langevin equation, we have revisited the problem of
      orbital motion of a charged particle in two dimensions for a normal magnetic
      field crossed with or without an in-plane electric bias. We are led to two
      interesting fluctuation effects: First, we obtain not only a longitudinal "work
      fluctuation" relation as expected for a barotropic type system, but also a
      transverse work-fluctuation relation perpendicular to the electric bias. This
      "Hall fluctuation" involves the product of the electric and the magnetic fields.
      Second, for the case of harmonic confinement without bias, the calculated
      probability density for the orbital magnetic moment gives nonzero even moments,
      not derivable as field derivatives of the classical free energy.

PMID- 19113175
TI  - Coherent transport on Apollonian networks and continuous-time quantum walks.
AB  - We study the coherent exciton transport on Apollonian networks generated by
      simple iterative rules. The coherent exciton dynamics is modeled by continuous
      time quantum walks and we calculate the transition probabilities between two
      nodes of the networks. We find that the transport depends on the initial nodes of
      the excitation. For networks up to the second generation the coherent transport
      shows perfect recurrences when the initial excitation starts at the central node.
      For networks of higher generation, the transport only shows partial revivals.
      Moreover, we find that the excitation is most likely to be found at the initial
      nodes while the coherent transport to other nodes has a very low probability. In
      the long time limit, the transition probabilities show characteristic patterns
      with identical values of limiting probabilities. Finally, the dynamics of quantum
      transport are compared with the classical transport modeled by continuous-time
      random walks.

PMID- 19113176
TI  - Missing levels in acoustic resonators.
AB  - It is shown that the deviations of the experimental statistics of six chaotic
      acoustic resonators from Wigner-Dyson random matrix theory predictions are
      explained by a recent model of random missing levels. In these resonatorsa made
      of aluminum plates a the larger deviations occur in the spectral rigidity (SRs)
      while the nearest-neighbor distributions (NNDs) are still close to the Wigner
      surmise. Good fits to the experimental NNDs and SRs are obtained by adjusting
      only one parameter, which is the fraction of remaining levels of the complete
      spectra. For two Sinai stadiums, one Sinai stadium without planar symmetry, two
      triangles, and a sixth of the three-leaf clover shapes, was found that 7%, 4%,
      7%, and 2%, respectively, of eigenfrequencies were not detected.

PMID- 19113177
TI  - Scale-free patterns at a saddle-node bifurcation in a stochastic system.
AB  - We demonstrate that scale-free patterns are observed in a spatially extended
      stochastic system whose deterministic part undergoes a saddle-node bifurcation.
      Remarkably, the scale-free patterns appear only at a particular time in
      relaxation processes from a spatially homogeneous initial condition. We
      characterize the scale-free nature in terms of the spatial configuration of the
      exiting time from a marginal saddle where the pair annihilation of a saddle and a
      node occurs at the bifurcation point. Critical exponents associated with the
      scale-free patterns are determined by numerical experiments.

PMID- 19113178
TI  - Mass transport of alkali metal with pulses in a surface reaction.
AB  - It is shown that the pulses which develop in the NO+H2 reaction on an alkali
      promoted Rh(110) surface reaction can transport alkali metal. This leads to the
      accumulation of a substantial alkali-metal concentration in the collision area of
      pulse trains. Realistic simulations revealed that the effect is due to the strong
      energetic interactions of the alkali metal with coadsorbates, i.e., the
      attractive interaction with coadsorbed oxygen and the effectively repulsive
      interaction with coadsorbed nitrogen.

PMID- 19113179
TI  - Chaotic scattering in the regime of weakly overlapping resonances.
AB  - We measure the transmission and reflection amplitudes of microwaves in a
      resonator coupled to two antennas at room temperature in the regime of weakly
      overlapping resonances and in a frequency range of 3-16GHz . Below 10.1GHz the
      resonator simulates a chaotic quantum system. The distribution of the elements of
      the scattering matrix S is not Gaussian. The Fourier coefficients of S are used
      for a best fit of the autocorrelation function of S to a theoretical expression
      based on random-matrix theory. We find very good agreement below but not above
      10.1GHz .

PMID- 19113180
TI  - Brownian demixing and wall effects in sedimenting suspensions of orientable
      particles.
AB  - We describe the Brownian demixing of sedimenting suspensions, a recently
      discovered phenomenon in which increases in the thermal energy can destabilize a
      system of orientable particles subjected to a torque to fluctuations in
      concentration. Through use of Brownian dynamics simulation and a mean-field
      analysis, we demonstrate that demixing occurs in a model system composed of
      slender rigid rods sedimenting between no-slip walls. Additionally, we describe
      the effects of wall separation distance on suspension stability.

PMID- 19113181
TI  - Spatiotemporal moving focus of long femtosecond-laser filaments in air.
AB  - The characteristics of filaments formed by femtosecond-laser pulses freely
      propagating in air are different from those of filaments generated with a focal
      lens. A scheme combining (2D+1) modeling of the nonlinear Schrodinger equation
      and ray-tracing method is proposed to provide a fast estimate of the long-range
      filamentation process in a single-filament regime. A filament with a length of
      more than 100m is formed by a 10-mJ , negative chirped 350-fs laser pulse freely
      propagating in air. A ray-tracing calculation based on the refractive index field
      obtained from the nonlinear Schrodinger simulation shows that, in the 100-m
      propagation range, the main mechanism of filamentation is the spatiotemporal
      moving focus induced by the initial distribution of the laser intensity. The
      analysis of ray trajectories suggests that the energy exchange between background
      and filament core due to refocusing of light rays can be induced by Kerr self
      focusing without the help of the ionization effect. The plasma defocusing can be
      observed only at a very short distance on the propagation track, and it prevents
      the collapse of the laser field.

PMID- 19113182
TI  - Reverse rotations in the circularly driven motion of a rigid body.
AB  - We study the dynamical response of a circularly driven rigid body, focusing on
      the description of intrinsic rotational behavior (reverse rotations). The model
      system we address is integrable but nontrivial, allowing for qualitative and
      quantitative analysis. A scale-free expression defining the separation between
      possible spinning regimes is obtained.

PMID- 19113183
TI  - Improving Wang-Landau sampling with adaptive windows.
AB  - Wang-Landau sampling (WLS) of large systems requires dividing the energy range
      into "windows" and joining the results of simulations in each window. The
      resulting density of states (and associated thermodynamic functions) is shown to
      suffer from boundary effects in simulations of lattice polymers and the five
      state Potts model. Here, we implement WLS using adaptive windows. Instead of
      defining fixed energy windows (or windows in the energy-magnetization plane for
      the Potts model), the boundary positions depend on the set of energy values on
      which the histogram is flat at a given stage of the simulation. Shifting the
      windows each time the modification factor f is reduced, we eliminate border
      effects that arise in simulations using fixed windows. Adaptive windows extend
      significantly the range of system sizes that may be studied reliably using WLS.

PMID- 19113184
TI  - Microcanonical analyses of homopolymer aggregation processes.
AB  - Using replica-exchange multicanonical Monte Carlo simulation, the aggregates of
      two homopolymers were numerically investigated through the microcanonical
      analysis method. The microcanonical entropy showed one convex function in the
      transition region, leading to a negative microcanonical specific heat. The origin
      of temperature backbending was the rearrangement of the segments during the
      process of aggregation; this aggregation process proceeded via a nucleation and
      growth mechanism. It was observed that the segments with a sequence number from
      10 to 13 in the polymer chain have leading effects on the aggregation.

PMID- 19113185
TI  - Dynamics of condensation in growing complex networks.
AB  - A condensation transition was predicted for growing technological networks
      evolving by preferential attachment and competing quality of their nodes, as
      described by the fitness model. When this condensation occurs, a node acquires a
      finite fraction of all the links of the network. Earlier studies based on steady
      state degree distribution and on the mapping to Bose-Einstein condensation were
      able to identify the critical point. Here we characterize the dynamics of
      condensation and we present evidence that below the condensation temperature
      there is a slow down of the dynamics and that a single node (not necessarily the
      best node in the network) emerges as the winner for very long times. The
      characteristic time t;{*} at which this phenomenon occurs diverges both at the
      critical point and at T-->0 when new links are attached deterministically to the
      highest quality node of the network.

PMID- 19113186
TI  - Kinetic equations modelling wealth redistribution: a comparison of approaches.
AB  - Kinetic equations modelling the redistribution of wealth in simple market
      economies is one of the major topics in the field of econophysics. We present a
      unifying approach to the qualitative study for a large variety of such models,
      which is based on a moment analysis in the related homogeneous Boltzmann
      equation, and on the use of suitable metrics for probability measures. In
      consequence, we are able to classify the most important feature of the steady
      wealth distribution, namely the fatness of the Pareto tail, and the dynamical
      stability of the latter in terms of the model parameters. Our results apply,
      e.g., to the market model with risky investments [S. Cordier, L. Pareschi, and G.
      Toscani, J. Stat. Phys. 120, 253 (2005)], and to the model with quenched saving
      propensities [A. Chatterjee, B. K. Chakrabarti, and S. S. Manna, Physica A 335,
      155 (2004)]. Also, we present results from numerical experiments that confirm the
      theoretical predictions.

PMID- 19113187
TI  - Escape problem under stochastic volatility: the Heston model.
AB  - We solve the escape problem for the Heston random diffusion model from a finite
      interval of span L . We obtain exact expressions for the survival probability
      (which amounts to solving the complete escape problem) as well as for the mean
      exit time. We also average the volatility in order to work out the problem for
      the return alone regardless of volatility. We consider these results in terms of
      the dimensionless normal level of volatility-a ratio of the three parameters that
      appear in the Heston model-and analyze their form in several asymptotic limits.
      Thus, for instance, we show that the mean exit time grows quadratically with
      large spans while for small spans the growth is systematically slower, depending
      on the value of the normal level. We compare our results with those of the Wiener
      process and show that the assumption of stochastic volatility, in an apparently
      paradoxical way, increases survival and prolongs the escape time. We finally
      observe that the model is able to describe the main exit-time statistics of the
      Dow-Jones daily index.

PMID- 19113188
TI  - Elastic nonlinearities in a one-dimensional model of fracture.
AB  - The dynamics of rapid brittle cracks is commonly studied in the framework of
      linear elastic fracture mechanics where nonlinearities are neglected. However,
      recent experimental and theoretical work demonstrated explicitly the importance
      of elastic nonlinearities in fracture dynamics. We study two simple one
      dimensional models of fracture in order to gain insights about the role of
      elastic nonlinearities and the implications of their exclusion in the common
      linear elastic approximation. In one model we consider the decohesion of a
      nonlinear elastic membrane from a substrate. In a second model we follow the
      philosophy of linear elastic fracture mechanics and study a linearized version of
      the nonlinear model. By analyzing the steady state solutions, the velocity-load
      relations and the response to perturbations of the two models we show that the
      linear approximation fails at finite crack tip velocities. We highlight certain
      features of the breakdown of the linear theory and discuss possible implications
      of our results to higher dimensional systems.

PMID- 19113189
TI  - Organization of modular networks.
AB  - We examine the global organization of heterogeneous equilibrium networks
      consisting of a number of well-distinguished interconnected parts-"communities"
      or modules. We develop an analytical approach allowing us to obtain the
      statistics of connected components and the intervertex distance distribution in
      these modular networks, and to describe their global organization and structure.
      In particular, we study the evolution of the intervertex distance distribution
      with an increasing number of interlinks connecting two infinitely large
      uncorrelated networks. We demonstrate that even a relatively small number of
      shortcuts unite the networks into one. In more precise terms, if the number of
      interlinks is any finite fraction of the total number of connections, then the
      intervertex distance distribution approaches a delta -function peaked form, and
      so the network is united.

PMID- 19113190
TI  - Pattern recognition with weighted complex networks.
AB  - In this paper we introduce a weighted complex networks model to investigate and
      recognize structures of patterns. The regular treating in pattern recognition
      models is to describe each pattern as a high-dimensional vector which however is
      insufficient to express the structural information. Thus, a number of methods are
      developed to extract the structural information, such as different feature
      extraction algorithms used in pre-processing steps, or the local receptive fields
      in convolutional networks. In our model, each pattern is attributed to a weighted
      complex network, whose topology represents the structure of that pattern. Based
      upon the training samples, we get several prototypal complex networks which could
      stand for the general structural characteristics of patterns in different
      categories. We use these prototypal networks to recognize the unknown patterns.
      It is an attempt to use complex networks in pattern recognition, and our result
      shows the potential for real-world pattern recognition. A spatial parameter is
      introduced to get the optimal recognition accuracy, and it remains constant
      insensitive to the amount of training samples. We have discussed the interesting
      properties of the prototypal networks. An approximate linear relation is found
      between the strength and color of vertexes, in which we could compare the
      structural difference between each category. We have visualized these prototypal
      networks to show that their topology indeed represents the common characteristics
      of patterns. We have also shown that the asymmetric strength distribution in
      these prototypal networks brings high robustness for recognition. Our study may
      cast a light on understanding the mechanism of the biologic neuronal systems in
      object recognition as well.

PMID- 19113191
TI  - Quantifying local structure effects in network dynamics.
AB  - Mutual information between the time series of two dynamical elements measures how
      well their activities are coordinated. In a network of interacting elements, the
      average mutual information over all pairs of elements I is a global measure of
      the correlation between the elements' dynamics. Local topological features in the
      network have been shown to affect I . Here we define a generalized clustering
      coefficient C_{p} and show that this quantity captures the effects of local
      structures on the global dynamics of networks. Using random Boolean networks
      (RBNs) as models of networks of interacting elements, we show that the variation
      of I ( I averaged over an ensemble of RBNs with the number of nodes N and average
      connectivity k ) with N and k is caused by the variation of C_{p} . Also, the
      variability of I between RBNs with equal N and k is due to their distinct values
      of C_{p} . Consequently, we propose a rewiring method to generate ensembles of
      BNs, from ordinary RBNs, with fixed values of C_{p} up to order 5, while
      maintaining in- and out-degree distributions. Using this methodology, the
      dependency of C_{p} on N and k and the variability of I for RBNs with equal N and
      k are shown to disappear in RBNs with C_{p} set to zero. The I of ensembles of
      RBNs with fixed, nonzero C_{p} values, also becomes almost independent of N and k
      . In addition, it is shown that C_{p} exhibits a power-law dependence on N in
      ordinary RBNs, suggesting that the C_{p} affects even relatively large networks.
      The method of generating networks with fixed C_{p} values is useful to generate
      networks with small N whose dynamics have the same properties as those of large
      scale networks, or to generate ensembles of networks with the same C_{p} as some
      specific network, and thus comparable dynamics. These results show how a system's
      dynamics is constrained by its local structure, suggesting that the local
      topology of biological networks might be shaped by selection, for example,
      towards optimizing the coordination between its components.

PMID- 19113192
TI  - Aging in the shear-transformation-zone theory of plastic deformation.
AB  - Aging phenomena in the plastic response of amorphous solids are studied within
      the theory of shear transformation zones (STZs), which describes the kinetic
      rearrangement of localized defects in response to external stress. To account for
      the slow, nonequilibrium dynamics after a quench below the glass transition
      temperature, two possible models are considered. In the first model, transition
      rates between the internal states of STZs decrease with time, while in the second
      model aging occurs due to the relaxation of an effective temperature that
      determines the number density of STZs and other out-of-equilibium degrees of
      freedom. It is shown that for reasonable choices of parameters, both models
      capture qualitatively typical aging features seen in computer simulations and
      experiments: (i) compliance curves measured for different waiting times t_{w}
      after the quench can be superimposed, when the observation times are rescaled
      with relaxation times proportional, variantt_{w};{mu} , 0<micro< or =1 , and (ii)
      stress-strain curves show a stationary plateau stress independent of t_{w} and a
      peak stress that increases logarithmically with both t_{w} and the strain rate.
      Trends of the aging behavior with the quench temperature are also discussed.

PMID- 19113193
TI  - Multifractality of random walks in the theory of vehicular traffic.
AB  - We investigate the origin of the experimentally observed multifractal scaling of
      vehicular traffic flows by studying a hydrodynamic model of traffic. We first
      extend and apply the formalism of generalized Hurst exponents H(q) to the case of
      random walkers that not only diffuse but rather also undergo nonlinear convection
      due to interactions with other walkers. We recover analytically, as expected,
      that H(q) equals 12 for a single random walker starting at the origin whose
      probability density function satisfies Burger's equation. Despite this result for
      a single walker, we find that for a collection of nonlinearly convecting
      diffusive particles, transient effects can give rise to multiscaling at given
      time scales for many initial conditions. In the Lighthill-Whitham-Richards
      hydrodynamic model of traffic, this multiscaling effect becomes more prominent
      for smaller diffusion constants and larger speed limits. We discuss the relevance
      of these findings for the realistic scenario of traffic that flows from small
      roads to large highways and vice versa, where transient effects can be expected
      to play a significant role.

PMID- 19113194
TI  - Synchronization of stochastic oscillations due to long-range diffusion.
AB  - We investigate the effect of long-range diffusive mixing on stochastic processes
      taking place on low-dimensional catalytic supports. As a working example, the
      cyclic lattice Lotka-Volterra (LLV) model is used which is conservative at the
      mean-field level and demonstrates fractal patterns and local oscillations when
      realized on low-dimensional lattice supports. We show that the local oscillations
      are synchronized when a weak, long-range, diffusive process is added to LLV and
      global oscillations of limit cycle type emerge. This phenomenon is demonstrated
      as a nonequilibrium phase transition and takes place when the mixing-to-reaction
      rate p (order parameter) is above a critical point p_{c} . The value of the
      critical point is shown to depend on the kinetic parameters. The global
      oscillations in this case emerge as a result of phase synchronization between
      local oscillations on sublattices.

PMID- 19113195
TI  - Trace formula for dielectric cavities: general properties.
AB  - The construction of the trace formula for open dielectric cavities is examined in
      detail. Using the Krein formula it is shown that the sum over cavity resonances
      can be written as a sum over classical periodic orbits for the motion inside the
      cavity. The contribution of each periodic orbit is the product of the two
      factors. The first is the same as in the standard trace formula and the second is
      connected with the product of reflection coefficients for all points of
      reflection with the cavity boundary. Two asymptotic terms of the smooth resonance
      counting function related with the area and the perimeter of a convex cavity are
      derived. The coefficient of the perimeter term differs from the one for closed
      cavities due to unusual high-energy asymptotics of the S matrix for the
      scattering on the cavity. Corrections to the leading semi-classical formula are
      briefly discussed. Obtained formulas agree well with numerical calculations for
      circular dielectric cavities.

PMID- 19113196
TI  - When Lyapunov exponents fail to exist.
AB  - We describe a simple continuous-time flow such that Lyapunov exponents fail to
      exist at nearly every point in the phase space R2 , despite the fact that the
      flow admits a unique natural measure. This example illustrates that the existence
      of Lyapunov exponents is a subtle question for systems that are not conservative.

PMID- 19113197
TI  - Dynamical trapping and chaotic scattering of the harmonically driven barrier.
AB  - A detailed analysis of the classical nonlinear dynamics of a single driven square
      potential barrier with harmonically oscillating position is performed. The system
      exhibits dynamical trapping which is associated with the existence of a stable
      island in phase space. Due to the unstable periodic orbits of the KAM structure,
      the driven barrier is a chaotic scatterer and shows stickiness of scattering
      trajectories in the vicinity of the stable island. The transmission function of a
      suitably prepared ensemble yields results which are very similar to tunneling
      resonances in the quantum mechanical regime. However, the origin of these
      resonances is different in the classical regime.

PMID- 19113198
TI  - Scaling investigation of Fermi acceleration on a dissipative bouncer model.
AB  - The phenomenon of Fermi acceleration is addressed for the problem of a classical
      and dissipative bouncer model, using a scaling description. The dynamics of the
      model, in both the complete and simplified versions, is obtained by use of a two
      dimensional nonlinear mapping. The dissipation is introduced using a restitution
      coefficient on the periodically moving wall. Using scaling arguments, we describe
      the behavior of the average chaotic velocities on the model both as a function of
      the number of collisions with the moving wall and as a function of the time. We
      consider variations of the two control parameters; therefore critical exponents
      are obtained. We show that the formalism can be used to describe the occurrence
      of a transition from limited to unlimited energy growth as the restitution
      coefficient approaches unity. The formalism can be used to characterize the same
      transition in two-dimensional time-varying billiard problems.

PMID- 19113199
TI  - Finite-size particles, advection, and chaos: a collective phenomenon of
      intermittent bursting.
AB  - We consider finite-size particles colliding elastically, advected by a chaotic
      flow. The collisionless dynamics has a quasiperiodic attractor and particles are
      advected towards this attractor. We show in this work that the collisions have
      dramatic effects in the system's dynamics, giving rise to collective phenomena
      not found in the one-particle dynamics. In particular, the collisions induce a
      kind of instability, in which particles abruptly spread out from the vicinity of
      the attractor, reaching the neighborhood of a coexisting chaotic saddle, in an
      autoexcitable regime. This saddle, not present in the dynamics of a single
      particle, emerges due to the collective particle interaction. We argue that this
      phenomenon is general for advected, interacting particles in chaotic flows.

PMID- 19113200
TI  - Scattering off an oscillating target: Basic mechanisms and their impact on cross
      sections.
AB  - We investigate classical scattering off a harmonically oscillating target in two
      spatial dimensions. The shape of the scatterer is assumed to have a boundary
      which is locally convex at any point and does not support the presence of any
      periodic orbits in the corresponding dynamics. As a simple example we consider
      the scattering of a beam of noninteracting particles off a circular hard
      scatterer. The performed analysis is focused on experimentally accessible
      quantities, characterizing the system, like the differential cross sections in
      the outgoing angle and velocity. Despite the absence of periodic orbits and their
      manifolds in the dynamics, we show that the cross sections acquire rich and
      multiple structure when the velocity of the particles in the beam becomes of the
      same order of magnitude as the maximum velocity of the oscillating target. The
      underlying dynamical pattern is uniquely determined by the phase of the first
      collision between the beam particles and the scatterer and possesses a universal
      profile, dictated by the manifolds of the parabolic orbits, which can be
      understood both qualitatively as well as quantitatively in terms of scattering
      off a hard wall. We discuss also the inverse problem concerning the possibility
      to extract properties of the oscillating target from the differential cross
      sections.

PMID- 19113201
TI  - Bifurcation analysis of solitary and synchronized pulses and formation of
      reentrant waves in laterally coupled excitable fibers.
AB  - We study the dynamics of a reaction-diffusion system comprising two mutually
      coupled excitable fibers. We consider a case in which the dynamical properties of
      the two fibers are nonidentical due to the parameter mismatch between them. By
      using the spatially one-dimensional FitzHugh-Nagumo equations as a model of a
      single excitable fiber, synchronized pulses are found to be stable in some
      parameter regime. Furthermore, there exists a critical coupling strength beyond
      which the synchronized pulses are stable for any amount of parameter mismatch. We
      show the bifurcation structures of the synchronized and solitary pulses and
      identify a codimension-2 cusp singularity as the source of the destabilization of
      synchronized pulses. When stable solitary pulses in both fibers disappear via a
      saddle-node bifurcation on increasing the coupling strength, a reentrant wave is
      formed. The parameter region, where a stable reentrant wave is observed in direct
      numerical simulation, is consistent with that obtained by bifurcation analysis.

PMID- 19113202
TI  - Fractional dynamics in the Levy quantum kicked rotor.
AB  - We investigate the quantum kicked rotor in resonance subjected to momentum
      measurements with a Levy waiting-time distribution. We find that the system has a
      sub-ballistic behavior. We obtain an analytical expression for the exponent of
      the power law of the variance as a function of the characteristic parameter of
      the Levy distribution. We also connect the anomalous diffusion found with a
      fractional dynamics.

PMID- 19113203
TI  - Method to control the coupling function using multilinear feedback.
AB  - Methods to control the dynamics of coupled oscillators have been developed owing
      to various medical and technological demands. In this study, we develop a method
      to control coupled oscillators in which the coupling function expressed in a
      phase model is regulated by the multilinear feedback. The present method has wide
      applicability because we do not need to measure an individual output from each
      oscillator, but only measure the sum of the outputs from all the oscillators.
      Moreover, it allows us to easily control the coupling function up to higher
      harmonics. The validity of the present method is confirmed through a simulation.

PMID- 19113204
TI  - Adaptive scheme for synchronization-based multiparameter estimation from a single
      chaotic time series and its applications.
AB  - Chaos-synchronization-based multiparameter estimation of a multiply delayed
      feedback system is investigated. We propose an adaptive method that can estimate
      all the parameters of the response system using the driving signal only. In the
      past few years, various methods have been developed for estimation of
      multiparameters of a chaotic system but most of them require more than one time
      series to estimate all the parameters of a chaotic or hyperchaotic system. The
      proposed method requires only a single chaotic time series to estimate all the
      parameters. A sufficient condition for synchronization is derived and it is shown
      that the numerical results well support the analytic calculations. The
      synchronized system has applications in cryptographic encoding for digital and
      analog signals, which is shown with an example.

PMID- 19113205
TI  - Moving boundary approximation for curved streamer ionization fronts: solvability
      analysis.
AB  - The minimal density model for negative streamer ionization fronts is
      investigated. An earlier moving boundary approximation for this model consisted
      of a "kinetic undercooling" type boundary condition in a Laplacian growth problem
      of Hele-Shaw type. Here we derive a curvature correction to the moving boundary
      approximation that resembles surface tension. The calculation is based on
      solvability analysis with unconventional features, namely, there are three
      relevant zero modes of the adjoint operator, one of them diverging; furthermore,
      the inner-outer matching ahead of the front must be performed on a line rather
      than on an extended region; and the whole calculation can be performed
      analytically. The analysis reveals a relation between the fields ahead and behind
      a slowly evolving curved front, the curvature and the generated conductivity.
      This relation forces us to give up the ideal conductivity approximation, and we
      suggest to replace it by a charge neutrality approximation. This implies that the
      electric potential in the streamer interior is no longer constant but solves a
      Laplace equation; this leads to a Muskat-type problem.

PMID- 19113206
TI  - Stabilizing continuous-wave output in semiconductor lasers by time-delayed
      feedback.
AB  - The stabilization of steady states is studied in a modified Lang-Kobayashi model
      of a semiconductor laser. We show that multiple time-delayed feedback, realized
      by a Fabry-Perot resonator coupled to the laser, provides a valuable tool for the
      suppression of unwanted intensity pulsations, and leads to stable continuous-wave
      operation. The domains of control are calculated in dependence on the feedback
      strength, delay time (cavity round trip time), memory parameter (mirror
      reflectivity), latency time, feedback phase, and bandpass filtering. Due to the
      optical feedback, multistable behavior can also occur in the form of delay
      induced intensity pulsations or other modes for certain choices of the control
      parameters. Control may then still be achieved by slowly ramping the injection
      current during turn-on.

PMID- 19113207
TI  - Periodic-orbit analysis and scaling laws of intermingled basins of attraction in
      an ecological dynamical system.
AB  - Chaotic dynamical systems with two or more attractors lying on invariant
      subspaces may, provided certain mathematical conditions are fulfilled, exhibit
      intermingled basins of attraction: Each basin is riddled with holes belonging to
      basins of the other attractors. In order to investigate the occurrence of such
      phenomenon in dynamical systems of ecological interest (two-species competition
      with extinction) we have characterized quantitatively the intermingled basins
      using periodic-orbit theory and scaling laws. The latter results agree with a
      theoretical prediction from a stochastic model, and also with an exact result for
      the scaling exponent we derived for the specific class of models investigated. We
      discuss the consequences of the scaling laws in terms of the predictability of a
      final state (extinction of either species) in an ecological experiment.

PMID- 19113208
TI  - Quantum mechanical potentials related to the prime numbers and Riemann zeros.
AB  - Prime numbers are the building blocks of our arithmetic; however, their
      distribution still poses fundamental questions. Riemann showed that the
      distribution of primes could be given explicitly if one knew the distribution of
      the nontrivial zeros of the Riemann zeta(s) function. According to the Hilbert
      Polya conjecture, there exists a Hermitian operator of which the eigenvalues
      coincide with the real parts of the nontrivial zeros of zeta(s) . This idea has
      encouraged physicists to examine the properties of such possible operators, and
      they have found interesting connections between the distribution of zeros and the
      distribution of energy eigenvalues of quantum systems. We apply the Marchenko
      approach to construct potentials with energy eigenvalues equal to the prime
      numbers and to the zeros of the zeta(s) function. We demonstrate the multifractal
      nature of these potentials by measuring the Renyi dimension of their graphs. Our
      results offer hope for further analytical progress.

PMID- 19113209
TI  - Amplitude death in time-delay nonlinear oscillators coupled by diffusive
      connections.
AB  - This paper analyzes the stability of the amplitude death phenomenon that occurs
      in a pair of scalar time-delay nonlinear oscillators coupled by static, dynamic,
      and delayed connections. Stability analysis shows that static connections never
      induce death in time-delay oscillators. Further, for the case of dynamic and
      delayed connections, a simple instability condition under which death never
      occurs is derived. A systematic procedure for estimating the boundary curves of
      death regions is also provided. These analytical results are then verified by
      electronic circuit experiments.

PMID- 19113210
TI  - Noise influence on pole solutions of the Sivashinsky equation for planar and
      outward propagating flames.
AB  - The dynamics of planar and outward propagating cylindrical flames has been
      studied in terms of exact solutions of the Sivashinsky equation with a random
      force term. The force term models the computational roundoff errors or a variety
      of perturbations of physical origins. In contrast to noiseless conditions, the
      number of poles in the system does not conserve and new poles appear due to the
      external forcing. It was found that modification of the pole solutions taking
      into account the appearance of new poles captures the features typical for the
      hydrodynamically unstable flames, which cannot be detected by the pole solutions
      with a fixed number of poles. Investigations based on the pole solutions make it
      possible to exclude the uncontrolled numerical noise that is always present in
      direct computations of the Sivashinsky equation, and to examine the interplay
      between noises and hydrodynamic instability. The study clearly demonstrates that
      the presence of noises is a necessary condition for flame acceleration.

PMID- 19113211
TI  - Flow properties of immiscible blends: Doi-Ohta model with active advection.
AB  - The interface between two immiscible fluids both is influenced (advected) by the
      imposed flow and influences (perturbs) it. The perturbation then changes the
      advection. This phenomenon is taken into account in an extended Doi-Ohta model of
      rheological behavior of immiscible blends. The agreement of the rheological
      predictions with experimental data is improved.

PMID- 19113212
TI  - Linear and nonlinear instabilities in rotating cylindrical Rayleigh-Benard
      convection.
AB  - Linear and nonlinear convection in a rotating annular cylinder, under
      experimental boundary conditions, heated from below and rotating about a vertical
      axis are investigated. In addition to the usual physical parameters such as the
      Rayleigh and Taylor number, an important geometric parameter, the ratio of the
      inner to outer radius, enters into the problem. For intermediate ratios, linear
      stability analysis reveals that there exist two countertraveling convective waves
      which are nonlinearly significant: a retrograde wave located near the outer
      sidewall and a prograde wave adjacent to the inner sidewall. Several interesting
      phenomena of nonlinear convection are found: (i) tempospatially modulated
      countertraveling waves caused by an instability of the Eckhaus-Benjamin-Feir
      type, (ii) destructive countertraveling waves in which the existence or
      disappearance of the prograde wave is determined by its relative phase to the
      retrograde wave, and (iii) a saddle-node-type bifurcation in which the prograde
      wave takes an infinite amount of time to pass over the retrograde wave.

PMID- 19113213
TI  - Solvability condition for the moving contact line.
AB  - We consider the motion of a contact line between a fluid, gas, and solid, as it
      occurs when a drop advances over a solid surface. This motion is controlled by a
      microscopic length scale near the contact line, such as a slip length or the
      precursor thickness. The capillary profile inside the drop is linked to the
      contact line through an intermediate region which is characterized by an
      interface slope which varies logarithmically. The intermediate solution contains
      a single adjustable constant, which can be computed either by matching to the
      capillary region or to the contact line. We describe a simple method to perform
      the matching and to compute the required constant. This extends and/or simplifies
      results known previously. We apply our results to the case of a spreading drop in
      the presence of an interface potential and derive the equation of motion by
      combining the inner and outer expansions.

PMID- 19113214
TI  - Non-Newtonian flow of dilute ferrofluids in a uniform magnetic field.
AB  - Nonequilibrium magnetization states predict non-Newtonian ferrofluid properties.
      It is desirable to understand the corresponding flow fields and characteristics.
      In this study, we derive a magnetoviscosity expression coming from the effective
      field method and describing the shear-thinning non-Newtonian behavior of dilute
      ferrofluids with finite magnetic anisotropy. A mathematical model is developed of
      non-Newtonian plane flow with respect to shear and pressure driving mechanisms in
      the presence of an applied stationary uniform magnetic field oriented in the
      direction perpendicular to vorticity. The results reveal that the non-Newtonian
      effect tends to increase the velocity and angular velocity but to reduce the
      magnetization strength. Moreover, an enhanced flow rate and reduced flow drag may
      be obtained. The maximum non-Newtonian effect is found at a ratio of the Neel
      relaxation time to the Brownian relaxation time of the order of 0.1.

PMID- 19113215
TI  - Impact of conditions at start-up on thermovibrational convective flow.
AB  - The development of thermovibrational convection in a cubic cell filled with high
      Prandtl number liquid (isopropanol) is studied. Direct nonlinear simulations are
      performed by solving three-dimensional Navier-Stokes equations in the Boussinesq
      approximation. The cell is subjected to high frequency periodic oscillations
      perpendicular to the applied temperature gradient under zero gravity. Two types
      of vibrations are imposed: either as a sine or cosine function of time. It is
      shown that the initial vibrational phase plays a significant role in the
      transient behavior of thermovibrational convective flow. Such knowledge is
      important to interpret correctly short-duration experimental results performed in
      microgravity, among which the most accessible are drop towers ( approximately 5s)
      and parabolic flights ( approximately 20s) . It is obtained that under sine
      vibrations, the flow reaches steady state within less than one thermal time.
      Under cosine acceleration, this time is 2 times longer. For cosine excitations,
      the Nusselt number is approximately 10 times smaller in comparison with the sine
      case. Besides, in the case of cosine, the Nusselt number oscillates with double
      frequency. However, at the steady state, time-averaged and oscillatory
      characteristics of the flow are independent of the vibrational start-up. The only
      feature that always differs the two cases is the phase difference between the
      velocity, temperature, and accelerations. We have found that due to nonlinear
      response of the system to the imposed vibrations, the phase shift between
      velocity and temperature is never equal exactly to pi2 , at least in
      weightlessness. Thus, heat transport always exists from the beginning of
      vibrations, although it might be weak.

PMID- 19113216
TI  - Fronts in randomly advected and heterogeneous media and nonuniversality of
      Burgers turbulence: theory and numerics.
AB  - A recently established mathematical equivalence-between weakly perturbed Huygens
      fronts (e.g., flames in weak turbulence or geometrical-optics wave fronts in
      slightly nonuniform media) and the inviscid limit of white-noise-driven Burgers
      turbulence-motivates theoretical and numerical estimates of Burgers-turbulence
      properties for specific types of white-in-time forcing. Existing mathematical
      relations between Burgers turbulence and the statistical mechanics of directed
      polymers, allowing use of the replica method, are exploited to obtain systematic
      upper bounds on the Burgers energy density, corresponding to the ground-state
      binding energy of the directed polymer and the speedup of the Huygens front. The
      results are complementary to previous studies of both Burgers turbulence and
      directed polymers, which have focused on universal scaling properties instead of
      forcing-dependent parameters. The upper-bound formula can be heuristically
      understood in terms of renormalization of a different kind from that previously
      used in combustion models, and also shows that the burning velocity of an
      idealized turbulent flame does not diverge with increasing Reynolds number at
      fixed turbulence intensity, a conclusion that applies even to strong turbulence.
      Numerical simulations of the one-dimensional inviscid Burgers equation using a
      Lagrangian finite-element method confirm that the theoretical upper bounds are
      sharp within about 15% for various forcing spectra (corresponding to various two
      dimensional random media). These computations provide a quantitative test of the
      replica method. The inferred nonuniversality (spectrum dependence) of the front
      speedup is of direct importance for combustion modeling.

PMID- 19113217
TI  - Formation of miscible fluid microstructures by hydrodynamic focusing in plane
      geometries.
AB  - We experimentally investigate the flow structures formed when two miscible fluids
      that have large viscosity contrasts are injected and hydrodynamically focused in
      plane microchannels. Parallel viscous flows composed of a central stream
      surrounded by symmetric sheath streams are examined as a function of the flow
      rates, fluid viscosities, and rates of molecular diffusion. We study miscible
      interfacial morphologies and show a route for manipulating viscous flow
      segregation processes in plane microsystems. The diffusion layer at the boundary
      of an ensheathed fluid grows as function of the distance downstream and depends
      on the Peclet number. In particular, we observe diffusion-enhanced viscous
      ensheathing processes. In the presence of a constriction, we investigate the
      formation of a lubricated viscous thread in the converging flow and also the
      buckling morphologies of the thread in the diverging flow. This study, relevant
      to multifluid flow between a "thick" material and a "thin" solvent, demonstrates
      the possibility to further control steady and oscillatory miscible fluid
      microstructures.

PMID- 19113218
TI  - Discreteness and resolution effects in rapidly rotating turbulence.
AB  - Rotating turbulence is characterized by the nondimensional Rossby number Ro,
      which is a measure of the strength of the Coriolis term relative to that of the
      nonlinear term. For rapid rotation (Ro-->0) , nonlinear interactions between
      inertial waves are weak, and the theoretical approaches used for other weak
      (wave) turbulence problems can be applied. The important interactions in rotating
      turbulence at small Ro become those between modes satisfying the resonant and
      near-resonant conditions. Often, discussions comparing theoretical results and
      numerical simulations are questioned because of a speculated problem regarding
      the discreteness of the modes in finite numerical domains versus continuous modes
      in unbounded continuous theoretical domains. This argument finds its origin in a
      previous study of capillary waves, for which resonant interactions have a very
      particular property that is not shared by inertial waves. This possible
      restriction on numerical simulations of rotating turbulence to moderate Ro has
      never been quantified. In this paper, we inquire whether the discreteness effects
      observed in capillary wave turbulence are also present in inertial wave
      turbulence at small Ro. We investigate how the discreteness effects can affect
      the setup and interpretation of studies of rapidly rotating turbulence in finite
      domains. In addition, we investigate how the resolution of finite numerical
      domains can affect the different types of nonlinear interactions relevant for
      rotating inertial wave turbulence theories. We focus on Rossby numbers ranging
      from 0 to 1 and on periodic domains due to their relevance to direct numerical
      simulations of turbulence. We find that discreteness effects are present for the
      system of inertial waves for Rossby numbers comfortably smaller than those used
      in the most recent numerical simulations of rotating turbulence. We use a
      kinematic model of the cascade of energy via selected types of resonant and near
      resonant interactions to determine the threshold of Ro below which discreteness
      effects become important enough to render an energy cascade impossible.

PMID- 19113219
TI  - Three-dimensional elastohydrodynamics of a thin plate oscillating above a wall.
AB  - We consider deflections of a thin rectangular elastic plate that is submerged
      within a Newtonian fluid. The plate is clamped along one edge and supported
      horizontally over a plane horizontal wall. We consider both external driving,
      where the clamped edge is vibrated vertically at high frequencies, and thermal
      driving, where the plate fluctuates under Brownian motion. In both cases, the
      amplitude of oscillation is assumed sufficiently small that the resulting flow
      has little convective inertia, although the oscillation frequency is sufficiently
      high to generate substantial unsteady inertia in the flow, a common scenario in
      many nano- and microdevices. We exploit the plate's thinness to develop an
      integral-equation representation for the three-dimensional flow (a so-called thin
      plate theory) which offers considerable computational savings over a full
      boundary-integral formulation. Limiting cases of high oscillation frequencies and
      small wall-plate separation distances are studied separately, leading to further
      simplified descriptions for the hydrodynamics. We validate these reduced integral
      representations against full boundary-integral computations, and identify the
      parameter ranges over which these simplified formulations are valid. Addressing
      the full flow-structure interaction, we also examine the limits of simpler two
      dimensional hydrodynamic models. We compare the responses of a narrow plate under
      two- and three-dimensional hydrodynamic loading, and report differences in the
      frequency response curves that occur when the plate operates in water, in
      contrast to the excellent agreement observed in air.

PMID- 19113220
TI  - Richtmyer-Meshkov instability in elastic-plastic media.
AB  - An analytical model for the linear Richtmyer-Meshkov instability in solids under
      conditions of high-energy density is presented, in order to describe the
      evolution of small perturbations at the solid-vacuum interface. The model shows
      that plasticity determines the maximum perturbation amplitude and provides simple
      scaling laws for it as well as for the time when it is reached. After the maximum
      amplitude is reached, the interface remains oscillating with a period that is
      determined by the elastic shear modulus. Extensive two-dimensional simulations
      are presented that show excellent agreement with the analytical model. The
      results suggest the possibility to experimentally evaluate the yield strength of
      solids under dynamic conditions by using a Richtmyer-Meshkov-instability-based
      technique.

PMID- 19113221
TI  - Interaction of electromagnetic waves with caustics in plasma flows.
AB  - An electromagnetic wave (EMW) interacting with the moving singularity of the
      charged particle flux undergoes the reflection and absorption as well as
      frequency change due to Doppler effect and nonlinearity. The singularity
      corresponding to a caustic in plasma flow with inhomogeneous velocity can arise
      during the breaking of the finite amplitude Langmuir waves due to nonlinear
      effects. A systematic analysis of the wave-breaking regimes and caustics
      formation is presented and the EMW reflection coefficients are calculated.

PMID- 19113222
TI  - Generation of intense proton beams from plastic targets irradiated by an
      ultraintense laser pulse.
AB  - Proton beams generated from thin aluminum and Mylar foil targets that are
      irradiated by a 30fs Ti:sapphire laser pulse with an intensity of
      2.2x10;{18}Wcm;{2} were investigated. Protons from the Mylar targets were
      observed to have an energy higher by a factor of 2 and were higher in number by
      an order of magnitude as compared with those generated from the aluminum targets.
      The maximum proton energy of 1.3+/-0.12MeV obtained from the Mylar target was
      found to be similar with previous observations that used laser pulses with
      different intensities. To address the anomalous behavior of the maximum proton
      energy for plastic targets, an acceleration model is proposed. In this model, the
      protons are accelerated by a resistively induced electric field in the front of
      the target, which can account for the experimental observations.

PMID- 19113223
TI  - Feasibility of a nitrogen-recombination soft-x-ray laser using capillary
      discharge Z pinch.
AB  - Capillary discharge Z pinches have been shown to be efficient drivers for x-ray
      lasers (XRLs). In this work we examine the possibility of realizing a H_{alpha}
      nitrogen recombination laser ( 3-->2 transition) at lambda=13.4nm , using a
      capillary discharge Z pinch. A pulsed power generator with 60kA peak current and
      70ns quarter period have been used to generate Z -pinch plasma in a 90-mm -long
      and 5-mm -diameter capillary. The plasma conditions were evaluated
      experimentally, using a filtered x-ray diode detector and time-integrated
      spectroscopy. The conditions required for the XRL were analytically estimated
      based on simple steady-state rate equations and then compared to experimental
      results. We demonstrated above 10% N7+ abundance at pinch time, while at least
      50% is required. Then, in the expansion phase, the plasma is cooled in a time
      less than 5ns to temperatures below 60eV , as needed for the recombination laser.
      These results suggest that the required conditions for nitrogen-recombination
      lasing could be achieved in a capillary discharge Z pinch, but a higher-power
      driver might be needed.

PMID- 19113224
TI  - Low ion-velocity slowing down in a strongly magnetized plasma target.
AB  - An ion projectile stopping at a velocity smaller than the target electron thermal
      velocity in a strong magnetic field is investigated within a different diffusion
      formulation, based on Green-Kubo integrands evaluated in magnetized one component
      plasma models, respectively framed on target ions and electrons. Analytic
      expressions are reported for slowing down orthogonal and parallel to an arbitrary
      large magnetic field, which are free from the usual uncertainties plaguing the
      standard perturbative derivations. Magnetic and target temperature dependences of
      the low velocity slowing down are thoroughly detailed for dense plasmas of fast
      ignition concern and ultracold plasmas envisioned for ion beam cooling, as well.

PMID- 19113225
TI  - Homogeneous nucleation in thermal dust-electron plasmas.
AB  - The homogeneous nucleation in the dust-electron plasma, which is formed in the
      zone of metal powder combustion products in the premixed laminar two-phase flame,
      has been studied. The classical nucleation theory has been used to determine the
      free energy and the critical radius of the nucleus. The influence of nucleus
      charging as a result of interaction between the nucleus and the electronic
      component of the plasma on the free energy has been determined. The dependence of
      the nucleus' critical radius on the plasma temperature and number density of the
      plasma's dust component has been determined. The proposed theoretical model shows
      that nucleation in the thermal dust-electron plasma is a self-consistent process,
      which is opposed to changing of the plasma's disperse structure.

PMID- 19113226
TI  - Phase-space structures in quantum-plasma wave turbulence.
AB  - The quasilinear theory of the Wigner-Poisson system in one spatial dimension is
      examined. Conservation laws and properties of the stationary solutions are
      determined. Quantum effects are shown to manifest themselves in transient
      periodic oscillations of the averaged Wigner function in velocity space. The
      quantum quasilinear theory is checked against numerical simulations of the bump
      on-tail and two-stream instabilities. The predicted wavelength of the
      oscillations in velocity space agrees well with the numerical results.

PMID- 19113227
TI  - Collisions between counter-rotating solitary vortices in the three-dimensional
      Ginzburg-Landau equation.
AB  - We report results of collisions between coaxial vortex solitons with topological
      charges +/-S in the complex cubic-quintic Ginzburg-Landau equation. With the
      increase of the collision momentum, merger of the vortices into one or two dipole
      or quadrupole clusters of fundamental solitons (for S=1 and 2, respectively) is
      followed by the appearance of pairs of counter-rotating "unfinished vortices," in
      combination with a soliton cluster or without it. Finally, the collisions become
      elastic. The clusters generated by the collisions are very robust, while the
      "unfinished vortices," eventually split into soliton pairs.

PMID- 19113228
TI  - Spatiotemporal dissipative solitons in two-dimensional photonic lattices.
AB  - We analyze spatiotemporal dissipative solitons in two-dimensional photonic
      lattices in the presence of gain and loss. In the framework of the continuous
      discrete cubic-quintic Ginzburg-Landau model, we demonstrate the existence of
      novel classes of two-dimensional spatiotemporal dissipative lattice solitons,
      which also include surface solitons located in the corners or at the edges of the
      truncated two-dimensional photonic lattice. We find the domains of existence and
      stability of such spatiotemporal dissipative solitons in the relevant parameter
      space, for both on-site and intersite lattice solitons. We show that the on-site
      solitons are stable in the whole domain of their existence, whereas most of the
      intersite solitons are unstable. We describe the scenarios of the instability
      induced dynamics of dissipative solitons in two-dimensional lattices.

PMID- 19113229
TI  - Bistability of a two-dimensional Klein-Gordon system as a reliable means to
      transmit monochromatic waves: a numerical approach.
AB  - Departing from a reliable computational method to approximate solutions of
      dissipative, nonlinear wave equations, we study the bistability of a (2+1) 
      dimensional sine-Gordon system, spatially defined on a bounded square of the
      first quadrant of the Cartesian plane, and subject to Dirichlet boundary data in
      the form of harmonic driving on the coordinate axes, oscillating at a frequency
      in the forbidden band gap of the medium. It is shown numerically that, as its
      spatially discrete counterpart, the continuous (2+1) -dimensional sine-Gordon
      equation presents the process of nonlinear supratransmission, and that this
      phenomenon is independent of the discretization procedure. Moreover, our
      simulations show that a bistable region, where a conducting state and an
      insulating state may coexist, is present in this system, even in the presence of
      external damping. As an application, it is shown that the bistable regime may be
      properly employed in order to transmit certain monochromatic waves through these
      media.

PMID- 19113230
TI  - Physical consequences of action conservation laws and their applications.
AB  - A class of conservation laws containing Hamilton's action integral is introduced
      for Lagrangian dynamical systems with a single degree of freedom and for the case
      when the Lagrangian function depends on the second time derivative of the
      coordinate. The action conservation laws are derived from the invariant
      properties of the Lagrange-D'Alembert differential variational principle with
      respect to infinitesimal transformations of the generalized coordinate and time
      by supposing that the generators of infinitesimal transformations depend on time,
      a generalized coordinate, and its first and second derivatives with respect to
      time. These action integral conservation laws are applied to the stability of
      columns, heat transfer, Thomas-Fermi problems, and other physical phenomena. A
      direct method for the approximate solution of these problems is combined with the
      Ritz variational method in order to obtain results of high accuracy.

PMID- 19113231
TI  - Acceleration of steady-state lattice Boltzmann simulations for exterior flows.
AB  - The simulation of a stationary fluid flow past an obstacle by the lattice
      Boltzmann method (LBM) in two dimensions is discussed. The combination of second
      order expressions for far-field boundary conditions and a suitable treatment of
      the no-slip boundary condition at the obstacle surface with the nested grid
      refinement technique can be applied to the LBM, resulting in a highly efficient
      method for the treatment of exterior flows. Furthermore, via replacing the nested
      time stepping by local time stepping, the resolution process can be substantially
      accelerated. A highly accurate drag coefficient was used to make an error
      assessment for various no-slip boundary conditions imposed on the obstacle
      surface. The analysis showed that the equilibrium method for treating the no-slip
      conditions is superior to halfway bounce-back and full-way bounce-back no-slip
      conditions when the relaxation time tau=1 . Also a tau -dependence test was made
      to evaluate the performance of different methods in the treatment of the no-slip
      boundary conditions.

PMID- 19113232
TI  - Accuracy of the lattice-Boltzmann method using the Cell processor.
AB  - Accelerator processors like the new Cell processor are extending the traditional
      platforms for scientific computation, allowing orders of magnitude more floating
      point operations per second (flops) compared to standard central processing
      units. However, they currently lack double-precision support and support for some
      IEEE 754 capabilities. In this work, we develop a lattice-Boltzmann (LB) code to
      run on the Cell processor and test the accuracy of this lattice method on this
      platform. We run tests for different flow topologies, boundary conditions, and
      Reynolds numbers in the range Re=6-350 . In one case, simulation results show a
      reduced mass and momentum conservation compared to an equivalent double-precision
      LB implementation. All other cases demonstrate the utility of the Cell processor
      for fluid dynamics simulations. Benchmarks on two Cell-based platforms are
      performed, the Sony Playstation3 and the QS20/QS21 IBM blade, obtaining a speed
      up factor of 7 and 21, respectively, compared to the original PC version of the
      code, and a conservative sustained performance of 28 gigaflops per single Cell
      processor. Our results suggest that choice of IEEE 754 rounding mode is possibly
      as important as double-precision support for this specific scientific
      application.

PMID- 19113233
TI  - Separation of variables in molecular-dynamics simulations: a criterion to
      estimate the quality of the approximation.
AB  - We propose a simple method to evaluate the approximation of separation of
      variables in molecular dynamics (MD) and related fields. It is based on a point
      by-point evaluation of the difference between the true potential and the
      corresponding potential where the separation of variables is applied. The major
      advantage of such an approach is the fact that it requires only the analytical
      form of the potential as provided in most of the MD codes. We provide two
      examples of application, namely, a diatomic molecule adsorbing on a flat surface
      and an alkane (aliphatic) chain.

PMID- 19113234
TI  - Computer simulations of isolated conductors in electrostatic equilibrium.
AB  - A computer simulation model is introduced to study the characteristics of
      isolated conductors in electrostatic equilibrium. Drawing an analogy between
      electrons and how they move to the surface of isolated conductors, we randomly
      initialize a large number of particles inside a small region at the center of
      simulated conductors and advance them according to their forces of repulsion. By
      use of optimized numerical techniques of the finite-size particle method
      associated with Poisson's equation, the particles are quickly advanced using a
      fast Fourier transform and their charge is efficiently shared using the clouds-in
      cells method. The particle populations in the simulations range from 50x10;{3} to
      1x10;{6} that move in various computation domains equal to 128x128 , 256x256 ,
      and 512x512 grids. When the particles come to an electrostatic equilibrium, they
      lie on the boundaries of the simulated conductors, from which the equilibrium
      properties are obtained. Consistent with the theory of electrostatics and charged
      conductors, we found that the particles move in response to the conductor
      geometry in such a way that the electrostatic energy is minimized. Good
      approximation results for the equilibrium properties were obtained using the
      proposed computer simulation model.

PMID- 19113235
TI  - Exact ground states of large two-dimensional planar Ising spin glasses.
AB  - Studying spin-glass physics through analyzing their ground-state properties has a
      long history. Although there exist polynomial-time algorithms for the two
      dimensional planar case, where the problem of finding ground states is
      transformed to a minimum-weight perfect matching problem, the reachable system
      sizes have been limited both by the needed CPU time and by memory requirements.
      In this work, we present an algorithm for the calculation of exact ground states
      for two-dimensional Ising spin glasses with free boundary conditions in at least
      one direction. The algorithmic foundations of the method date back to the work of
      Kasteleyn from the 1960s for computing the complete partition function of the
      Ising model. Using Kasteleyn cities, we calculate exact ground states for huge
      two-dimensional planar Ising spin-glass lattices (up to 3000;{2} spins) within
      reasonable time. According to our knowledge, these are the largest sizes
      currently available. Kasteleyn cities were recently also used by Thomas and
      Middleton in the context of extended ground states on the torus. Moreover, they
      show that the method can also be used for computing ground states of planar
      graphs. Furthermore, we point out that the correctness of heuristically computed
      ground states can easily be verified. Finally, we evaluate the solution quality
      of heuristic variants of the L. Bieche approach.

PMID- 19113236
TI  - Revised moment propagation method for scalar transport.
AB  - The moment propagation (MP) method was used to study the transport of a passive
      scalar by a turbulent fluid. Numerical results show that the MP method does not
      accurately capture the evolution of a scalar field at moderate Reynolds numbers.
      A theoretical analysis proves that the diffusivity derived from the MP model
      depends on fluid velocity, which limits the range of Peclet number. We describe
      an improved MP model (MP2) which eliminates the velocity-dependent diffusion,
      leading to more accurate predictions of scalar transport in high-velocity flows;
      at low velocities both methods give similar results. We test the model for a
      variety of simple flows and find that accurate results can be obtained at grid
      Peclet numbers in excess of 10.

PMID- 19113237
TI  - Directed update for the stochastic Green function algorithm.
AB  - In a recent paper we presented a stochastic Green function (SGF) algorithm, which
      has the properties of being general and easy to apply to any lattice Hamiltonian
      of the form H[over ]=V[over ]-T[over ] , where V[over ] is diagonal in the chosen
      occupation number basis and T[over ] has only positive matrix elements. We
      propose here a modified version of the update scheme that keeps the simplicity
      and generality of the original SGF algorithm, and significantly enhances its
      efficiency.

PMID- 19113238
TI  - Monte Carlo simulation and linear stability analysis of Turing pattern formation
      in reaction-subdiffusion systems.
AB  - Subdiffusion is an important physical phenomenon observed in many systems.
      However, numerical techniques to study it, especially when coupled to reactions,
      are lacking. In this paper, we develop an efficient Monte Carlo algorithm based
      on the Gillespie algorithm and the continuous-time random walk to simulate
      reaction-subdiffusion systems. Using this algorithm, we investigate Turing
      pattern formation in the Schnakenberg model with subdiffusion. First, we show
      that, as the system becomes more subdiffusive, the homogeneous state becomes more
      difficult to destablize and Turing patterns form less easily. Second, we show
      that, as the number of particles in the system decreases, the magnitude of
      fluctuations increases and again the Turing patterns form less easily. Third, we
      show that, as the system becomes more subdiffusive, the ratio between the two
      diffusive constants must be higher in order to observe Turing patterns. Finally,
      we also carry out linear stability analysis to validate the results obtained from
      our algorithm.

PMID- 19113239
TI  - Contact line dynamics in binary lattice Boltzmann simulations.
AB  - We show that, when a single relaxation time lattice Boltzmann algorithm is used
      to solve the hydrodynamic equations of a binary fluid for which the two
      components have different viscosities, strong spurious velocities in the steady
      state lead to incorrect results for the equilibrium contact angle. We identify
      the origins of these spurious currents and demonstrate how the results can be
      greatly improved by using a lattice Boltzmann method based on a multiple
      relaxation-time algorithm. By considering capillary filling we describe the
      dependence of the advancing contact angle on the interface velocity.

PMID- 19113240
TI  - Normal-form approach to spatiotemporal pattern formation in globally coupled
      electrochemical systems.
AB  - We show that the experimental global coupling (GC) of spatially extended
      electrochemical oscillators is weak close to a supercritical Hopf bifurcation. A
      center manifold reduction allows then the normal form which comprises the GC and
      the naturally existing nonlocal (migration) coupling (NLC) to be derived. We show
      that the interaction between NLC and GC widens the spectrum of coherent
      structures found in globally coupled oscillatory media and allows for wavelength
      selection of standing waves, stabilization of phase clusters without breaking
      phase invariance, and creation of heteroclinic networks connecting families of
      oscillatory states characterized by different spatial symmetries.

PMID- 19113241
TI  - Tristability in the pendula chain.
AB  - Experiments on a chain of coupled pendula driven periodically at one end
      demonstrate the existence of a regime which produces an output frequency at an
      odd fraction of the driving frequency. The stationary state is then obtained with
      numerical simulations and modeled with an analytical solution of the continuous
      sine-Gordon equation that resembles a kinklike motion back and forth in the
      restricted geometry of the chain. This solution differs from the expressions used
      to understand nonlinear bistability where the synchronization constraint was the
      basic assumption. As a result the short pendula chain is shown to possess
      tristable stationary states and to act as a frequency divider.

PMID- 19113242
TI  - Suppression of reverse flows in pumping by induced-charge electro-osmosis using
      asymmetrically stacked elliptical metal posts.
AB  - Several researchers have analyzed pumps that employ induced-charge electro
      osmosis (ICEO) using mainly coplanar electrode array structures in a lateral
      electric field. We propose ICEO pumps that remove reverse flows using
      asymmetrically stacked elliptical metal posts and numerically examine the pumping
      performance. By the boundary element method along with double layer
      approximation, we find that the asymmetrical stacking configuration efficiently
      suppresses the unwanted reverse flow and yields velocities of the order of a few
      millimeters per second, and this configuration is compatible with that of an
      optimized half-coating pump. Further, we propose a simple model for the stacking
      pump and predict that the velocity of such a stacking pump with a thin limit is
      larger than 67% of that of a circular cylindrical half-coating pump of the same
      length. Using this stacking pump, we can expect to significantly improve the
      pumping performance.

PMID- 19113243
TI  - All-optical suppression of relativistic self-focusing of laser beams in plasmas.
AB  - It is demonstrated that a catastrophic relativistic self-focusing (RSF) of a high
      power laser pulse can be prevented all-optically by a second, much weaker,
      copropagating pulse. RSF suppression occurs when the difference frequency of the
      pulses slightly exceeds the electron plasma frequency. The mutual defocusing is
      caused by the three-dimensional electron density perturbation driven by the laser
      beat wave slightly above the plasma resonance. A bienvelope model describing the
      early stage of the mutual defocusing is derived and analyzed. Later stages,
      characterized by the presence of a strong electromagnetic cascade, are
      investigated numerically. Stable propagation of the laser pulse with weakly
      varying spot size and peak amplitude over several Rayleigh lengths is predicted.

PMID- 19113244
TI  - States of the Dirac equation in confining potentials.
AB  - We study the Dirac equation in confining potentials with pure vector coupling,
      proving the existence of metastable states with longer and longer lifetimes as
      the nonrelativistic limit is approached and eventually merging with continuity
      into the Schrodinger bound states. The existence of these states could concern
      high energy models and possible resonant scattering effects in systems like
      graphene. We present numerical results for the linear and the harmonic cases and
      we show that the density of the states of the continuous spectrum is well
      described by a sum of Breit-Wigner lines. The width of the line with lowest
      positive energy well reproduces the Schwinger pair production rate for a linear
      potential: this gives an explanation of the Klein paradox for bound states and a
      new concrete way to get information on pair production in unbounded, nonuniform
      electric fields, where very little is known.

PMID- 19113245
TI  - Efficient hidden-variable simulation of measurements in quantum experiments.
AB  - We prove that the results of a finite set of general quantum measurements on an
      arbitrary dimensional quantum system can be simulated using a polynomial (in
      measurements) number of hidden-variable states. In the limit of infinitely many
      measurements, our method gives models with the minimal number of hidden-variable
      states, which scales linearly with the number of measurements. These results can
      find applications in foundations of quantum theory, complexity studies, and
      classical simulations of quantum systems.

PMID- 19113246
TI  - Foundation of statistical mechanics under experimentally realistic conditions.
AB  - We demonstrate the equilibration of isolated macroscopic quantum systems,
      prepared in nonequilibrium mixed states with a significant population of many
      energy levels, and observed by instruments with a reasonably bound working range
      compared to the resolution limit. Both properties are satisfied under many, if
      not all, experimentally realistic conditions. At equilibrium, the predictions and
      limitations of statistical mechanics are recovered.

PMID- 19113247
TI  - Stable suspension and dispersion-induced transitions from repulsive Casimir
      forces between fluid-separated eccentric cylinders.
AB  - We numerically demonstrate a stable mechanical suspension of a silica cylinder
      within a metallic cylinder separated by ethanol, via a repulsive Casimir force
      between the silica and the metal. We investigate cylinders with both circular and
      square cross sections, and show that the latter exhibit a stable orientation as
      well as a stable position, via a method to compute Casimir torques for finite
      objects. Furthermore, the stable orientation of the square cylinder undergoes a
      45 degrees transition as the separation length scale is varied, which is
      explained as a consequence of material dispersion.

PMID- 19113248
TI  - Magnetic dipolar interaction in a Bose-Einstein condensate atomic interferometer.
AB  - We study the role played by the magnetic dipole interaction in the decoherence of
      a lattice-based interferometer that employs an alkali Bose-Einstein condensate
      with a tunable scattering length. The different behavior we observe for two
      different orientations of the dipoles gives us evidence of the anisotropic
      character of the interaction. The experiment is correctly reproduced by a model
      we develop only if the long-range interaction between different lattice sites is
      taken into account. Our model indicates that dipolar interaction can be
      compensated by a proper choice of the scattering length and that the magnetic
      dipole interaction should not represent an obstacle for atom interferometry with
      Bose-Einstein condensates with a tunable interaction.

PMID- 19113249
TI  - Long-range correlations of density in a Bose-Einstein condensate expanding in a
      random potential.
AB  - We study correlations of atomic density in a weakly interacting Bose-Einstein
      condensate, expanding diffusively in a random potential. We show that these
      correlations are long range and that they are strongly enhanced at long times.
      The density at distant points exhibits negative correlations.

PMID- 19113250
TI  - Generation of narrow-band polarization-entangled photon pairs for atomic quantum
      memories.
AB  - We report an experimental realization of a narrow band polarization-entangled
      photon source with a linewidth of 9.6 MHz through cavity-enhanced spontaneous
      parametric down-conversion. This linewidth is comparable to the typical linewidth
      of atomic ensemble-based quantum memories. Single-mode output is realized by
      setting a reasonable cavity length difference between different polarizations,
      using of temperature controlled etalons and actively stabilizing the cavity. The
      entangled property is characterized with quantum state tomography, giving a
      fidelity of 94% between our state and a maximally entangled state. The coherence
      length is directly measured to be 32 m through two-photon interference.

PMID- 19113251
TI  - Quantum phase tomography of a strongly driven qubit.
AB  - The interference between repeated Landau-Zener transitions in a qubit swept
      through an avoided level crossing results in Stuckelberg oscillations in qubit
      magnetization, a hallmark of the coherent strongly driven regime in two-level
      systems. The two-dimensional Fourier transforms of the resulting oscillatory
      patterns are found to exhibit a family of one-dimensional curves in Fourier
      space, in agreement with recent observations in a superconducting qubit. We
      interpret these images in terms of time evolution of the quantum phase of the
      qubit state and show that they can be used to probe dephasing mechanisms.

PMID- 19113252
TI  - Novel schemes for directly measuring entanglement of general states.
AB  - An intrinsic relation between maximally entangled states and entanglement
      measures is revealed, which plays a role in establishing connections for
      different entanglement quantifiers. We exploit the basic idea and propose a
      framework to construct schemes for directly measuring entanglement of general
      states. In particular, we demonstrate that rank-1 local factorizable projective
      measurements, which are achievable with only one copy of an entangled state
      involved at a time in a sequential way, are sufficient to directly determine the
      concurrence of an arbitrary two-qubit entangled state.

PMID- 19113253
TI  - Single-photon excitation of surface plasmon polaritons.
AB  - We provide the quantum-mechanical description of the excitation of surface
      plasmon polaritons on metal surfaces by single photons. An attenuated-reflection
      setup is described for the quantum excitation process in which we find remarkably
      efficient photon-to-surface plasmon wave-packet transfer. Using a fully quantized
      treatment of the fields, we introduce the Hamiltonian for their interaction and
      study the quantum statistics during transfer with and without losses in the
      metal.

PMID- 19113254
TI  - Tracking heterogeneous dynamics during the alpha relaxation of a simple glass
      former.
AB  - We study the relaxation process in a simple glass former--the Kob-Andersen
      lattice gas model. We show that, for this model, structural relaxation is due to
      slow percolation of regions of cooperatively moving particles, which leads to
      heterogeneous dynamics of the system. We find that the size distribution of these
      regions is given by a power law and that their formation is encoded in the
      initial structure of the particles, with the memory of initial configuration
      increasingly retained with increasing density.

PMID- 19113255
TI  - Interplay between Anderson and Stark localization in 2D lattices.
AB  - This Letter studies the dynamics of a quantum particle in 2D lattices with on
      site disorder in the presence of a static field. It is shown that the particle is
      localized along the field direction, while in the orthogonal direction to the
      field it shows diffusive dynamics for algebraically large times. For weak
      disorder an analytical expression for the diffusion coefficient is obtained by
      mapping the problem to a band random matrix. This expression is confirmed by
      numerical simulations of the particle's dynamics, which also indicate the
      existence of a universal equation for the diffusion coefficient, valid for an
      arbitrary disorder strength.

PMID- 19113256
TI  - Critical asymmetry for giant diffusion of active Brownian particles.
AB  - We study the effect of an asymmetry on the transport properties of an active
      Brownian particle. We demonstrate the existence of a critical force or, more
      generally, of a critical asymmetry that separates parameter regimes of giant
      diffusion from those with reliable directed transport. We derive a condition for
      the critical asymmetry by means of an exact expression for the diffusion
      coefficient and by a simplified discrete picture. A critical asymmetry, as
      predicted by the simple model, is also found in a detailed model of coupled
      molecular motors displaying bidirectional motion.

PMID- 19113257
TI  - Coulomb suppression of the stellar enhancement factor.
AB  - It is commonly assumed that reaction measurements for astrophysics should be
      preferably performed in the direction of a positive Q value to minimize the
      impact of the stellar enhancement factor, i.e., the difference between the
      laboratory rate and the actual stellar rate. We show that the stellar effects can
      be minimized in the charged particle channel, even when the reaction Q value is
      negative. As a demonstration, the cross section of the astrophysically relevant
      85Rb(p,n)85Sr reaction has been measured by activation between 2.16 < or = Ec.m.
      < or = 3.96 MeV and the astrophysical reaction rate for (p, n) as well as (n, p)
      is directly inferred from the data. The presented arguments are also relevant for
      other alpha- and proton-induced reactions in the p and rp processes.
      Additionally, our results confirm a previously derived modification of a global
      optical proton potential.

PMID- 19113258
TI  - Colorful horizons with charge in anti-de Sitter space.
AB  - An Abelian gauge symmetry can be spontaneously broken near a black hole horizon
      in anti-de Sitter space using a condensate of non-Abelian gauge fields. A second
      order phase transition is shown to separate Reissner-Nordstrom-anti-de Sitter
      solutions from a family of symmetry-breaking solutions which preserve a diagonal
      combination of gauge invariance and spatial rotational invariance.

PMID- 19113260
TI  - New measurement of the K+-->pi+ nunu branching ratio.
AB  - Three events for the decay K+-->pi+ nunu have been observed in the pion momentum
      region below the K+-->pi+pi0 peak, 140 < Ppi < 199 MeV/c, with an estimated
      background of 0.93+/-0.17(stat.) -0.24+0.32(syst.) events. Combining this
      observation with previously reported results yields a branching ratio of B(K+-
      >pi+ nunu) = (1.73(-1.05)+1.15) x 10(-10) consistent with the standard model
      prediction.

PMID- 19113261
TI  - Observation of Upsilon(2S)-->etaUpsilon(1S) and search for related transitions.
AB  - We report the first observation of Upsilon(2S)-->etaUpsilon(1S), with a branching
      fraction B=(2.1(-0.6)+0.7(stat)+/-0.3(syst)) x 10(-4) and a statistical
      significance 5.3sigma. Data were acquired with the CLEO III detector at the CESR
      e+e(-) symmetric collider. This is the first process observed involving a b-quark
      spin flip. For related transitions, 90% confidence limits in units of 10(-4) are
      B(Upsilon(2S)-->pi0Upsilon(1S)) < 1.8, B(Upsilon(3S)-->etaUpsilon(1S)) < 1.8,
      B(Upsilon(3S)-->pi0Upsilon(1S)) < 0.7, and B(Upsilon(3S)-->pi0Upsilon(2S)) < 5.1.

PMID- 19113263
TI  - Locating multiple self-consistent field solutions: an approach inspired by
      metadynamics.
AB  - We propose a method to locate the solutions to the self-consistent field (SCF)
      equations, using an approach based upon metadynamics. We define a distance
      function between density matrices. Within an SCF calculation, when a solution is
      found, a biasing potential based on distance from the solution is added to the
      energy to avoid reconvergence to the same solution. Multiple solutions can
      therefore be relatively easily found. Using this method we locate all known
      solutions and one unknown solution of the H4 model. The set of restricted Hartree
      Fock (RHF) solutions for the nitrogen molecule is located, and a broken-symmetry
      solution lower in energy than the symmetric RHF solution is found corresponding
      to dissociation into doublet fragments.

PMID- 19113264
TI  - Polarization control in two-color above-threshold ionization of atomic helium.
AB  - Two-color multiphoton ionization of atomic helium was investigated by combining
      extreme ultraviolet (XUV) radiation from the Free Electron Laser in Hamburg with
      an intense synchronized optical laser. In the photoelectron spectrum, lines
      associated with direct ionization and above-threshold ionization show strong
      variations of their amplitudes as a function of both the intensity of the optical
      dressing field and the relative orientation of the linear polarization vectors of
      the two fields. The polarization dependence provides direct insight into the
      symmetry of the outgoing electrons in above-threshold ionization. In the high
      field regime, the monochromaticity of the XUV radiation enables the unperturbed
      observation of nonlinear processes in the optical field.

PMID- 19113265
TI  - Strong field ionization rate for arbitrary laser frequencies.
AB  - A simple, analytical, nonrelativistic ionization rate formula for atoms and
      positive ions in intense ultraviolet and x-ray electromagnetic fields is derived.
      The rate is valid at arbitrary values of the Keldysh parameter and confirmed by
      results from ab initio numerical solutions of the single active electron, time
      dependent Schrodinger equation. The proposed rate is particularly relevant for
      experiments employing the new free electron laser sources.

PMID- 19113266
TI  - Orthopositronium lifetime: analytic results in O(alpha) and O(alpha3lnalpha).
AB  - We present the O(alpha) and O(alpha3lnalpha) corrections to the total decay width
      of orthopositronium in closed analytic form, in terms of basic irrational
      numbers, which can be evaluated numerically to arbitrary precision.

PMID- 19113267
TI  - Frequency shifts in an optical lattice clock due to magnetic-dipole and electric
      quadrupole transitions.
AB  - We report a hitherto undiscovered frequency shift for forbidden J = 0-->J = 0
      clock transitions excited in atoms confined to an optical lattice. These shifts
      result from magnetic-dipole and electric-quadrupole transitions, which have a
      spatial dependence in an optical lattice that differs from that of the stronger
      electric-dipole transitions. In combination with the residual translational
      motion of atoms in an optical lattice, this spatial mismatch leads to a frequency
      shift via differential energy level spacing in the lattice wells for ground state
      and excited state atoms. We estimate that this effect could lead to fractional
      frequency shifts as large as 10(-16), which might prevent lattice-based optical
      clocks from reaching their predicted performance levels. Moreover, these effects
      could shift the magic wavelength in lattice clocks in three dimensions by as much
      as 100 MHz, depending on the lattice configuration.

PMID- 19113268
TI  - Effect of nonlinearity on adiabatic evolution of light.
AB  - We investigate the effect of nonlinearity in a system described by an
      adiabatically evolving Hamiltonian. Experiments are conducted in a three-core
      waveguide structure that is adiabatically varying with distance, in analogy to
      the stimulated Raman adiabatic passage process in atomic physics. In the linear
      regime, the system exhibits an adiabatic power transfer between two waveguides
      which are not directly coupled, with negligible power recorded in the
      intermediate coupling waveguide. In the presence of nonlinearity the adiabatic
      light passage is found to critically depend on the excitation power. We show how
      this effect is related to the destruction of the dark state formed in this
      configuration.

PMID- 19113269
TI  - Optical BLOCH oscillations and Zener tunneling with nonclassical light.
AB  - A quantum theory of optical Bloch oscillations and Zener tunneling (ZT) in arrays
      of coupled waveguides is theoretically presented, and the particlelike behavior
      of photons undergoing ZT is highlighted. In singly-periodic arrays excited by a
      photon-number-state input beam, each photon behaves as a classical particle which
      independently undergoes a coin-toss ZT event with a probability described by
      classical Zener theory. In binary arrays, excitation with two tilted beams
      enables us to observe the Hong-Ou-Mandel interference for two photons undergoing
      Bloch-Zener oscillations.

PMID- 19113270
TI  - Antisymmetric polar modes of thermal convection in rotating spherical fluid
      shells at high taylor numbers.
AB  - The onset of thermal convection in a rotating spherical shell of intermediate
      radius ratio eta=0.4 is studied numerically for Taylor numbers Ta > or = 10(11)
      and the Prandtl number of the liquid sodium (sigma=0.01). For the first time, it
      is shown that at very high Taylor numbers the first unstable mode can be
      antisymmetric with respect to the equator and confined inside a cylinder tangent
      to the inner sphere at the equator (polar mode). The exponent of the power law
      determined from the asymptotic dependence of the critical Rayleigh number for
      very high Ta is 0.57, lower than 2/3, given theoretically for the spiraling
      columnar modes, and than 0.63, found numerically for the outer equatorially
      attached modes.

PMID- 19113271
TI  - Anomalous hydrodynamic drafting of interacting flapping flags.
AB  - In aggregates of objects moving through a fluid, bodies downstream of a leader
      generally experience reduced drag force. This conventional drafting holds for
      objects of fixed shape, but interactions of deformable bodies in a flow are
      poorly understood, as in schools of fish. In our experiments on "schooling"
      flapping flags, we find that it is the leader of a group who enjoys a significant
      drag reduction (of up to 50%), while the downstream flag suffers a drag increase.
      This counterintuitive inverted drag relationship is rationalized by dissecting
      the mutual influence of shape and flow in determining drag. Inverted drafting has
      never been observed with rigid bodies, apparently due to the inability to deform
      in response to the altered flow field of neighbors.

PMID- 19113259
TI  - Measurement of the forward-backward charge asymmetry and extraction of
      sin2thetaWeff in pp-->Z/gamma* + X-->e+e- +X events produced at sqrt[s] = 1.96
      TeV.
AB  - We present a measurement of the forward-backward charge asymmetry (A FB) in pp-
      >Z/gamma* + X-->e+e(-) + X events at a center-of-mass energy of 1.96 TeV using
      1.1 fb(-1) of data collected with the D0 detector at the Fermilab Tevatron
      collider. A FB is measured as a function of the invariant mass of the electron
      positron pair, and found to be consistent with the standard model prediction. We
      use the A FB measurement to extract the effective weak mixing angle sin2thetaWeff
      = 0.2326+/-0.0018(stat)+/-0.0006(syst).

PMID- 19113272
TI  - Electrorheological fluid dynamics.
AB  - We use the Onsager principle to derive a two-phase continuum formulation for the
      hydrodynamics of the electrorheological (ER) fluid, consisting of dielectric
      microspheres dispersed in an insulating liquid. Predictions of the theory are in
      excellent agreement with the experiments. In particular, it is shown that whereas
      the usual configuration of applied electric field being perpendicular to the
      shearing direction can lead to shear thinning at high shear rates and thus the
      loss of ER effect, the interdigitated, alternating electrodes configuration can
      eliminate the shear-thinning effect.

PMID- 19113273
TI  - Turbulence-condensate interaction in two dimensions.
AB  - We present experimental results on turbulence generated in thin fluid layers in
      the presence of a large-scale coherent flow, or a spectral condensate. It is
      shown that the condensate modifies the third-order velocity moment in a much
      wider interval of scales than the second one. The modification may include the
      change of sign of the third moment in the inverse cascade. This observation may
      help resolve a controversy on the energy flux in mesoscale atmospheric turbulence
      (10-500 km): to recover a correct energy flux from the third velocity moment one
      needs first to subtract the coherent flow. We find that the condensate also
      increases the velocity flatness.

PMID- 19113274
TI  - Is the scaling of supersonic turbulence universal?
AB  - The statistical properties of turbulence are considered to be universal at
      sufficiently small length scales, i.e., independent of boundary conditions and
      large-scale forces acting on the fluid. Analyzing data from numerical simulations
      of supersonic turbulent flow driven by external forcing, we demonstrate that this
      is not generally true for the two-point velocity statistics of compressible
      turbulence. However, a reformulation of the refined similarity hypothesis in
      terms of the mass-weighted velocity rho1/3v yields scaling laws that are almost
      insensitive to the forcing. The results imply that the most intermittent
      dissipative structures are shocks closely following the scaling of Burgers
      turbulence.

PMID- 19113275
TI  - Probing the hydrogen melting line at high pressures by dynamic compression.
AB  - We investigate the capabilities of dynamic compression by intense heavy ion beams
      to yield information about the high pressure phases of hydrogen. Employing ab
      initio simulations and experimental data, a new wide range equation of state for
      hydrogen is constructed. The results show that the melting line up to its maximum
      as well as the transition from molecular fluids to fully ionized plasmas can be
      tested with the beam parameters soon to be available. We demonstrate that x-ray
      scattering can distinguish between phases and dissociation states.

PMID- 19113276
TI  - Evidence from numerical simulations of transport-barrier relaxations in tokamak
      edge plasmas in the presence of electromagnetic fluctuations.
AB  - The dynamics of transport barriers in fusion plasmas is studied in the presence
      of electromagnetic fluctuations. The work is based on numerical simulations using
      a new three-dimensional electromagnetic fluid turbulence code (EMEDGE3D). In
      these simulations, the transport-barrier exhibits intermittent relaxation cycles.
      It is found that magnetic fluctuations have a negligible influence on the
      relaxation process while the magnetic activity is enhanced during these
      relaxations, in agreement with experimental observations.

PMID- 19113277
TI  - Observation of an ultracold plasma instability.
AB  - We present the first observation of an instability in an expanding ultracold
      plasma. We observe periodic emission of electrons from an ultracold plasma in
      weak, crossed magnetic and electric fields, and a strongly perturbed electron
      density distribution in electron time-of-flight projection images. We identify
      this instability as a high-frequency electron drift instability due to the
      coupling between the electron drift wave and electron cyclotron harmonic, which
      has large wave numbers corresponding to wavelengths close to the electron
      gyroradius.

PMID- 19113278
TI  - Dusty-plasma liquid in the statistical theory of the liquid state.
AB  - Measurements in dusty plasmas were carried out to find the region of validity of
      approximate relation in statistical theory of liquid states. The integral
      equations with the Percus-Yewick and the hypernetted-chain closures as well as
      the superposition approximation were chosen as the objects for investigation. The
      range of validity of these approaches was obtained by the use of experimental
      methods for analysis of spatial correlation of dust particles in plasma.

PMID- 19113279
TI  - Resonance cone interaction with a self-consistent radio-frequency sheath.
AB  - We study the propagation of lower-hybrid-type resonance cones in a tenuous
      magnetized plasma, and, in particular, their interaction with, and reflection
      from, the plasma sheath near a conducting wall. The sheath is modeled as a vacuum
      gap whose width is given by the Child-Langmuir law. The application of interest
      is when the resonance cones are launched (parasitically) by an ion-cyclotron
      radio-frequency antenna in a typical rf-heated tokamak fusion experiment. We
      calculate the fraction of launched voltage in the resonance cones that is
      transmitted to the sheath, and show that it has a sensitive thresholdlike turn on
      when a critical parameter reaches order unity. Above threshold, the fractional
      voltage transmitted to the sheath is order unity, leading to strong and
      potentially deleterious rf-wall interactions in tokamak rf heating experiments.
      Below threshold, these interactions can be avoided.

PMID- 19113280
TI  - Observation of plasma rotation driven by static nonaxisymmetric magnetic fields
      in a tokamak.
AB  - We present the first evidence for the existence of a neoclassical toroidal
      rotation driven in a direction counter to the plasma current by nonaxisymmetric,
      nonresonant magnetic fields. At high beta and with large injected neutral beam
      momentum, the nonresonant field torque slows down the plasma toward the
      neoclassical "offset" rotation rate. With small injected neutral beam momentum,
      the toroidal rotation is accelerated toward the offset rotation, with resulting
      improvement in the global energy confinement time. The observed magnitude,
      direction, and radial profile of the offset rotation are consistent with
      neoclassical theory predictions.

PMID- 19113262
TI  - Search for the flavor-changing neutral-current decay t-->Zq in pp collisions at
      sqrt[s] = 1.96 TeV.
AB  - We report a search for the flavor-changing neutral-current decay of the top quark
      t-->Zq (q=u, c) in pp collisions at sqrt[s]=1.96 TeV using a data sample
      corresponding to an integrated luminosity of 1.9 fb(-1) collected by the CDF II
      detector. This decay is strongly suppressed in the standard model and an
      observation of a signal at the Fermilab Tevatron would be an indication of
      physics beyond the standard model. Using Z+ > or = 4 jet final state candidate
      events, with and without an identified bottom quark jet, we obtain an upper limit
      of B(t-->Zq) < 3.7% at 95% C.L.

PMID- 19113281
TI  - Torsional stick-slip behavior in WS2 nanotubes.
AB  - We experimentally observed atomic-scale torsional stick-slip behavior in
      individual nanotubes of tungsten disulfide (WS2). When an external torque is
      applied to a WS2 nanotube, all its walls initially stick and twist together,
      until a critical torsion angle, at which the outer wall slips and twists around
      the inner walls, further undergoing a series of stick-slip torque oscillations.
      We present a theoretical model based on density-functional-based tight-binding
      calculations, which explains the torsional stick-slip behavior in terms of a
      competition between the effects of the in-plane shear stiffness of the WS2 walls
      and the interwall friction arising from the atomic corrugation of the interaction
      between adjacent WS2 walls.

PMID- 19113283
TI  - Mixed mobile ion effect and cooperative motions in silver-sodium phosphate
      glasses.
AB  - The conduction pathways and the extraordinary weak mixed mobile ion effect (MMIE)
      in AgxNa1-xPO3 glasses have been investigated by bond-valence analysis of reverse
      Monte Carlo produced structural models. We find that the MMIE is suppressed in
      this system due to a common cooperative hopping process, where both Ag and Na
      participate. This finding is in strong contrast to glass systems exhibiting a
      pronounced MMIE, where the two types of mobile ions have distinctly different
      conduction pathways and the M ions tend to block the pathways for the N ions and
      vice versa.

PMID- 19113282
TI  - Spectroscopic signatures of novel oxygen-defect complexes in stoichiometrically
      controlled CdSe.
AB  - Growth of single crystals of CdSe with oxygen, introduced by stoichiometric
      control to suppress the formation of native Se and Cd vacancies, generates oxygen
      centers replacing Cd (O Cd) rather than Se (O Se) as expected. This antisite
      substitution is unambiguously singled out by the host isotope fine structure of
      the nearest neighbor (NN) Se atoms in the localized vibrational modes (LVMs) of O
      Cd. When the stoichiometry control favors the formation of Cd vacancies, three
      infrared signatures gamma1, gamma2 and gamma3 appear ascribable to the LVMs of O
      Se in association with a Cd vacancy in the NN position as (O Se-V Cd) centers.
      Polarization measurements establish the monoclinic Cs symmetry for these centers.
      As a function of temperature, they display a remarkable two-step symmetry
      transformation, Cs-->C3v-->Td, due to the dynamic switching of the O Se-V Cd
      dangling bond.

PMID- 19113284
TI  - Electron damage to supported ice investigated by scanning tunneling microscopy
      and spectroscopy.
AB  - We study the interaction of low-energy electrons with crystalline ice (D2O) on
      Cu(111) by low-temperature scanning tunneling microscopy and spectroscopy.
      Electrons induce dissociation of the molecules with a threshold of approximately
      3 eV. The large dissociation yield of the order of 10(-8)/electron and the
      extended area of dissociation are attributed to a shift in conduction band during
      the dissociation. Voltage dependent differences in imaging of ice and dissociated
      ice are reflected in the spectroscopic signature.

PMID- 19113285
TI  - Geometric principles of surface growth.
AB  - I introduce a new equation describing epitaxial growth processes. This equation
      is derived from a simple variational geometric principle and it has a
      straightforward interpretation in terms of continuum and microscopic physics. It
      is also able to reproduce the critical behavior already observed, mound formation
      and mass conservation, but however does not fit a divergence form as the most
      commonly spread models of conserved surface growth. This formulation allows me to
      connect the results of the dynamic renormalization group analysis with intuitive
      geometric principles, whose generic character may well allow them to describe
      surface growth and other phenomena in different areas of physics.

PMID- 19113286
TI  - Dual-surfactant effect to enhance p-type doping in III-V semiconductor thin
      films.
AB  - Surfactant effects are usually achieved by the addition of a single surface
      element. We demonstrate by first-principles calculations a dual-surfactant effect
      of Sb and H on enhancing Zn doping in organometallic vapor phase epitaxially
      grown GaP thin films. The combined effects of Sb and H lower significantly the
      doping energy of Zn in GaP, while neither Sb nor H can function alone as an
      effective surfactant. Our finding suggests a general strategy for enhancing p
      type doping of III-V semiconductors by using a metallic-element with H as dual
      surfactants.

PMID- 19113287
TI  - Steady-state nonequilibrium density of States of driven strongly correlated
      lattice models in infinite dimensions.
AB  - An exact formalism for calculating the retarded and advanced Green's functions of
      strongly correlated lattice models in a uniform electric field is derived within
      dynamical mean-field theory. To illustrate the method, we solve for the
      nonequilibrium density of states of the Hubbard model in both the metallic and
      Mott-insulating phases at half-filling (with an arbitrary strength electric
      field) by employing the approximate numerical renormalization group as the
      impurity solver. This general approach can be applied to any strongly correlated
      lattice model in the limit of large dimensions.

PMID- 19113288
TI  - Field-induced spin-ice-like orders in spin liquid Tb2Ti2O7.
AB  - We have studied the field-induced magnetic structures in Tb2Ti2O7, in a wide
      temperature (0.3 < T < 270 K) and field (0 < H < 7 T) range, by single crystal
      polarized and unpolarized neutron diffraction, with H parallel[110] axis. A
      ferromagneticlike structure with k = 0 propagation vector is induced, whose local
      order at low field and low temperature is akin to spin ice. The four Tb ions
      separate in alpha and beta chains having different values of the magnetic
      moments, which is quantitatively explained by taking the crystal field anisotropy
      into account. Above 2 T and below 2 K, an antiferromagneticlike structure with k
      = (0,0,1) is induced besides the k = 0 structure. It shows a reentrant behavior
      and extends over a finite length scale. It occurs together with a broadening of
      the nuclear peaks, which suggests a field-induced distortion and magnetostriction
      effect.

PMID- 19113289
TI  - Coulomb barrier for charge separation at an organic semiconductor interface.
AB  - Charge transfer (CT) excitons across donor-acceptor interfaces are believed to be
      barriers to charge separation in organic solar cells, but little is known about
      their physical characteristics. Here, we probe CT excitons on a crystalline
      pentacene surface using time-resolved two-photon photoemission spectroscopy. CT
      excitons of 1s, 2s, and 3s characters are bound by Coulomb energies of 0.43,
      0.21, 0.12 eV, respectively, in agreement with quantum mechanical modeling. The
      large binding energy of the 1s CT exciton excludes its participation in
      photovoltaics. Efficient charge separation in organic heterojunction solar cells
      must involve a series of hot CT excitons.

PMID- 19113290
TI  - Coherent particle transfer in an on-demand single-electron source.
AB  - Electron transfer from a localized state in a quantum dot into a ballistic
      conductor generally results in particle-hole excitations. We study this effect,
      considering a resonance level with time-dependent energy coupled to particle
      states in the Fermi sea. We find that, as the resonance level is driven through
      the Fermi-level, particle-hole excitations can be suppressed for certain driving
      protocols. In particular, such noiseless transfer occurs if the level moves with
      constant rapidity, its energy changing linearly with time. A scheme to study the
      coherence of particle transfer is proposed.

PMID- 19113291
TI  - Measurement of the optical conductivity of graphene.
AB  - Optical reflectivity and transmission measurements over photon energies between
      0.2 and 1.2 eV were performed on single-crystal graphene samples on a SiO2
      substrate. For photon energies above 0.5 eV, graphene yielded a spectrally flat
      optical absorbance of (2.3+/-0.2)%. This result is in agreement with a constant
      absorbance of pialpha, or a sheet conductivity of pie2/2h, predicted within a
      model of noninteracting massless Dirac fermions. This simple result breaks down
      at lower photon energies, where both spectral and sample-to-sample variations
      were observed. This "nonuniversal" behavior is explained by including the effects
      of doping and finite temperature, as well as contributions from intraband
      transitions.

PMID- 19113292
TI  - STM images of subsurface Mn atoms in GaAs: evidence of hybridization of surface
      and impurity states.
AB  - We show that scanning tunneling microscopy (STM) images of subsurface Mn atoms in
      GaAs are formed by hybridization of the impurity state with intrinsic surface
      states. They cannot be interpreted in terms of bulk-impurity wave-function
      imaging. Atomic-resolution images obtained using a low-temperature apparatus are
      compared with advanced, parameter-free tight-binding simulations accounting for
      both the buckled (110) surface and vacuum electronic properties. Splitting of the
      acceptor state due to buckling is shown to play a prominent role.

PMID- 19113293
TI  - Pfaffian statistics through adiabatic transport in the 1D coherent state
      representation.
AB  - Recent work has shown that the low energy sector of certain quantum Hall states
      is adiabatically connected to simple charge-density-wave patterns that appear,
      e.g., when the system is deformed into a thin torus. Here it is shown that the
      patterns emerging in this limit already determine the non-Abelian statistics of
      the nu=1 Moore-Read state. Aside from the knowledge of these patterns, the method
      only relies on the principle of adiabatic continuity, the effectively
      noncommutative geometry in a strong magnetic field, and topological as well as
      locality arguments.

PMID- 19113294
TI  - Adsorbate-limited conductivity of graphene.
AB  - We present a theory of electronic transport in graphene in the presence of
      randomly placed adsorbates. Our analysis predicts a marked asymmetry of the
      conductivity about the Dirac point, as well as a negative weak-localization
      magnetoresistivity. In the region of strong scattering, renormalization group
      corrections drive the system further towards insulating behavior. These results
      explain key features of recent experiments, and are validated by numerical
      transport computations.

PMID- 19113295
TI  - Unscreened Coulomb interactions and the quantum spin Hall phase in neutral zigzag
      graphene ribbons.
AB  - A study of the effect of unscreened Coulomb interactions on the quantum spin Hall
      phase of finite-width neutral zigzag graphene ribbons is presented. By solving a
      tight-binding Hamiltonian that includes the intrinsic spin-orbit (ISO)
      interaction, exact expressions for band structures and edge-state wave functions
      are obtained. These analytic results, supported by tight-binding calculations,
      show that chiral spin-filtered edge states are composed of localized and damped
      oscillatory wave functions, reminiscent of the ones obtained in armchair ribbons.
      The addition of long-range Coulomb interactions opens a gap in the charge sector
      with a gapless spin sector. In contrast to armchair terminations, the charge gap
      vanishes exponentially with the ribbon width and its amplitude and decay length
      are strongly dependent on the ISO coupling. Comparison with reported ab initio
      calculations are presented.

PMID- 19113296
TI  - Tunable spin gaps in a quantum-confined geometry.
AB  - We have studied the interplay of a giant spin-orbit splitting and of quantum
      confinement in artificial Bi-Ag-Si trilayer structures. Angle-resolved
      photoelectron spectroscopy reveals the formation of a complex spin-dependent gap
      structure, which can be tuned by varying the thickness of the Ag buffer layer.
      This provides a means to tailor the electronic structure at the Fermi energy,
      with potential applications for silicon-compatible spintronic devices.

PMID- 19113297
TI  - Magnetic dispersion of the diagonal incommensurate phase in lightly doped La2
      xSrxCuO4.
AB  - We present inelastic neutron scattering experiments on a single-domain crystal of
      lightly doped La1.96Sr0.04CuO4. We find that the magnetic excitation spectrum in
      this insulating phase with a diagonal incommensurate spin modulation is
      remarkably similar to that in the superconducting regime, where the spin
      modulation is bond parallel. In particular, we find that the dispersion slope at
      low energy is essentially independent of doping and temperature over a
      significant range. The energy at which the excitations cross the commensurate
      antiferromagnetic wave vector increases roughly linearly with doping through the
      underdoped regime.

PMID- 19113298
TI  - Current induced decomposition of Abrikosov vortices in p-n layered
      superconductors and heterostructures.
AB  - We describe the decomposition of Abrikosov vortices into decoupled pancake
      vortices in superconductors having both electron and hole charge carriers. We
      estimate the critical current of such a decomposition, at which a superconducting
      normal state transition occurs, and find that it is very sensitive to the
      magnetic field and temperature. The effect can be observed in recently
      synthesized self-doped high-Tc layered superconductors with electrons and holes
      coexisting in different Cu-O planes and in artificial p-n superconductor
      heterostructures. The sensitivity of the critical current to a magnetic field may
      be used for sensors and detectors of a magnetic field, which can be built up from
      the superconductor heterostructures.

PMID- 19113299
TI  - Na4Ir3O8 as a 3D spin liquid with fermionic spinons.
AB  - Spin liquid states for the spin-1/2 antiferromagnetic Heisenberg model on a
      hyperkagome lattice are studied. We classify and study flux states according to
      symmetries. Applying this model to Na4Ir3O8, we propose that the high temperature
      state may be described by a spinon Fermi surface, which forms a paired state with
      line nodes below 20 K. The possible mixed spin singlet and spin triplet pairing
      states are discussed according to the lattice symmetry which breaks inversion.

PMID- 19113300
TI  - Gapless spin liquids on the three-dimensional hyperkagome lattice of Na4Ir3O8.
AB  - Recent experiments indicate that Na4Ir3O8, a material in which s=1/2 Ir local
      moments live on a three-dimensional "hyperkagome" lattice of corner-sharing
      triangles, may have a quantum spin liquid ground state with gapless spin
      excitations. Using a combination of exact diagonalization, symmetry analysis of
      fermionic mean field ground states and Gutzwiller projected variational wave
      functions studies, we propose a quantum spin liquid with spinon Fermi surfaces as
      a favorable candidate for the ground state of the Heisenberg model on this
      lattice. We point out implications of this proposal for thermodynamic properties
      and discuss possible weak instabilities of the spinon Fermi surfaces.

PMID- 19113301
TI  - Dynamical backaction of microwave fields on a nanomechanical oscillator.
AB  - We measure the response and thermal motion of a high-Q nanomechanical oscillator
      coupled to a superconducting microwave cavity in the resolved-sideband regime
      where the oscillator's resonance frequency exceeds the cavity's linewidth. The
      coupling between the microwave field and mechanical motion is strong enough for
      radiation pressure to overwhelm the intrinsic mechanical damping. This radiation
      pressure damping cools the fundamental mechanical mode by a factor of 5 below the
      thermal equilibrium temperature in a dilution refrigerator to a phonon occupancy
      of 140 quanta.

PMID- 19113302
TI  - Polarization selective magnetic vortex dynamics and core reversal in rotating
      magnetic fields.
AB  - We report on the observation of magnetic vortex dynamics in response to rotating
      magnetic fields in submicron platelets. Unlike linear fields or spin polarized
      currents, which excite both vortex core polarization states, an in-plane rotating
      field can selectively excite one of the polarization states. We demonstrate by
      direct imaging with time-resolved scanning x-ray microscopy that the rotating
      field only excites the gyrotropic mode if the rotation sense of the field
      coincides with the vortex gyration sense and that such a field can selectively
      reverse the vortex polarization.

PMID- 19113303
TI  - Evidence for universal scaling in the spin-glass phase.
AB  - We perform Monte Carlo simulations of Ising spin-glass models in three and four
      dimensions, as well as of Migdal-Kadanoff spin glasses on a hierarchical lattice.
      Our results show strong evidence for universal scaling in the spin-glass phase in
      all three models. Not only does this allow for a clean way to compare results
      obtained from different coupling distributions, it also suggests that a so far
      elusive renormalization group approach within the spin-glass phase may actually
      be feasible.

PMID- 19113304
TI  - Magnetic bistability and nucleation of magnetic bubbles in a layered 2D organic
      based magnet [Fe(TCNE)(NCMe)2][FeCl4].
AB  - The 2D layered organic-based magnet [Fe(TCNE)(NCMe)2][FeCl4]
      (TCNE=tetracyanoethylene) exhibits a unique macroscopic magnetic bistability
      between the field-cooled and zero-field-cooled states, which cannot be explained
      by either superparamagnetic behavior or spin freezing due to spin glass order.
      This magnetic bistability is described through consideration of the ensemble of
      uncoupled 2D Ising layers and their magnetization reversal initiated by a field
      induced nucleation of magnetic bubbles in individual layers. The bubble
      nucleation rate strongly depends on the external field and temperature resulting
      in anomalous magnetic relaxation.

PMID- 19113305
TI  - Rotation of an electric polarization vector by rotating magnetic field in
      cycloidal magnet Eu0.55Y0.45MnO3.
AB  - To clarify the microscopic origin of the gigantic magnetoelectric effect in
      multiferroics, we have investigated the variation of an electric polarization (P)
      vector under a rotating magnetic field (H) for a cycloidal helimagnet
      Eu0.55Y0.45MnO3 as a canonical example. P rotates smoothly by rotating H around
      the magnetic propagation wave vector k, which can be well understood by the
      rotation of the conical spin structure around k. We also show that the rotation
      process of the conical spin structure under H is crucial for the retention or
      reversal of the spin helicity or equivalently of the direction of P.

PMID- 19113306
TI  - Probing superexchange interaction in molecular magnets by spin-flip spectroscopy
      and microscopy.
AB  - The superexchange mechanism in cobalt phthalocyanine (CoPc) thin films was
      studied by a low temperature scanning tunneling microscope. The CoPc molecules
      were found to form one-dimensional antiferromagnetic chains in the film.
      Collective spin excitations in individual molecular chains were measured with
      spin-flip associated inelastic electron tunneling spectroscopy. By spatially
      mapping the spin-flipping channels with submolecular precision, we are able to
      explicitly identify the specific molecular orbitals that mediate the
      superexchange interaction between molecules.

PMID- 19113307
TI  - Constructing an array of anchored single-molecule rotors on gold surfaces.
AB  - Molecular rotors with a fixed off-center rotation axis have been observed for
      single tetra-tert-butyl zinc phthalocyanine molecules on an Au(111) surface by a
      scanning tunneling microscope at LN2 temperature. Experiments and first
      principles calculations reveal that we introduce gold adatoms at the surface as
      the stable contact of the molecule to the surface. An off-center rotation axis is
      formed by a chemical bonding between a nitrogen atom of the molecule and a gold
      adatom at the surface, which gives them a well-defined contact while the
      molecules can have rotation-favorable configurations. Furthermore, these single
      molecule rotors self-assemble into large scale ordered arrays on Au(111)
      surfaces. A fixed rotation axis off center is an important step towards the
      eventual fabrication of molecular motors or generators.

PMID- 19113308
TI  - Fano profiles induced by near-field coupling in heterogeneous dimers of gold and
      silver nanoparticles.
AB  - The near-field coupling between a gold and a silver spherical nanoparticle is
      investigated theoretically. Fano profiles are observed in the absorption cross
      section of the gold nanoparticle due to the coupling between the spectrally
      localized surface plasmon resonance of the silver nanoparticle and the continuum
      of interband transitions of the gold one. The effect of dimer internal
      characteristics (particle sizes and distance), surrounding medium (through the
      refractive index), and external excitation (polarization and propagation
      directions) are addressed. In particular, it is shown that the near-field
      coupling can be tuned from the weak to the strong regime by rotating the
      polarization direction, and that the Fano profiles are sensitive to the shadowing
      effect even for small particle sizes.

PMID- 19113309
TI  - Ferroelectricity-induced coupling between light and terahertz-frequency acoustic
      phonons in BaTiO3/SrTiO3 superlattices.
AB  - We report a UV-Raman study of folded acoustic vibrations in epitaxial
      ferroelectric BaTiO3/SrTiO3 superlattices. The folded acoustic doublets show an
      anomalous temperature dependence disappearing above the ferroelectric transition,
      which is tuned by varying the thickness of the BaTiO3 and SrTiO3 layers. A
      mechanism involving the acoustic phonon modulation of the spatially periodic
      ferroelectric polarization explains the observed temperature dependence. These
      results demonstrate the strong coupling between sound, charge, and light in these
      multifunctional nanoscale ferroelectrics.

PMID- 19113310
TI  - Electronic and mechanical coupling of carbon nanotubes: a tunable resonant Raman
      study of systems with known structures.
AB  - We report on the first tunable resonant Raman scattering study performed on
      suspended isolated and coupled single-wall carbon nanotubes, unambiguously
      identified by electron diffraction. Besides the confirmation of the relation
      between the structural properties, the radial breathing frequency and the optical
      resonances for isolated metallic nanotubes, we evidence that interacting
      nanotubes experience drastic modifications of their resonance fingerprints. We
      first demonstrate a degeneracy lifting of an electronic level in a bundle of
      identical zigzag nanotubes. We then show the existence of a strong energy
      transfer mediated by a mechanical coupling between two nonidentical bundled
      nanotubes.

PMID- 19113311
TI  - Ultrafast electronic phase transition in La1/2Sr3/2MnO4 by coherent vibrational
      excitation: evidence for nonthermal melting of orbital order.
AB  - An ultrafast electronic phase transition, associated with melting of orbital
      order, is driven in La1/2Sr3/2MnO4 by selectively exciting the Mn-O stretching
      mode with femtosecond pulses at 16 microm wavelength. The energy coupled into
      this vibration is less than 1% of that necessary to induce the transition
      thermally. Nonthermal melting of this electronic phase originates from coherent
      lattice displacements comparable to the static Jahn-Teller distortion.

PMID- 19113312
TI  - Cooperative response of Pb(ZrTi)O3 nanoparticles to curled electric fields.
AB  - We investigate cooperative responses, as well as a microscopic mechanism for
      vortex switching, in Pb(Zr0.5Ti0.5)O3 nanoparticles under curled electric fields.
      We find that the domain coexistence mechanism is not valid for toroid switching.
      Instead dipoles display unusual collective behavior by forming a new vortex with
      a perpendicular (not opposite) toroid moment. The correlation between the new and
      original vortices is revealed to be critical for reversing the toroid moment. We
      further describe a technological approach that is able to drastically reduce the
      curled electric field needed for vortex switching.

PMID- 19113313
TI  - Nature of dynamical coupling between polarization and strain in nanoscale
      ferroelectrics from first principles.
AB  - A first-principle-based technique is used to investigate dynamical coupling
      between polarization and picosecond time-scale strain pulses in ferroelectric
      nanolayers. Two different dynamical mechanisms are found. The first mechanism
      concerns homogeneous dipole patterns, is governed by the ultrafast soft-mode
      dynamics, mostly consists in the modification of the dipoles' magnitude, and
      leads to a polarization only weakly changing and following the strain pulse via
      an "usual" coupling law. On the other hand, the second mechanism occurs in highly
      inhomogeneous dipole patterns, is characterized by a large change in polarization
      and by a time delay between polarization and strain, and is governed by the
      "slower breathing" of dipolar inhomogeneities. This second mechanism provides a
      successful explanation of puzzling experimental data.

PMID- 19113314
TI  - Experimental test of curvature-driven dynamics in the phase ordering of a two
      dimensional liquid crystal.
AB  - We study electric field driven deracemization in an achiral liquid crystal
      through the formation and coarsening of chiral domains. It is proposed that
      deracemization in this system is a curvature-driven process. We test this
      prediction using the recently obtained exact result for the distribution of hull
      enclosed areas in two-dimensional coarsening with nonconserved scalar order
      parameter dynamics [J. J. Arenzon et al., Phys. Rev. Lett. 98, 145701 (2007)].
      The experimental data are in very good agreement with the theory. We thus
      demonstrate that deracemization in such bent-core liquid crystals belongs to the
      Allen-Cahn universality class, and that the exact formula, which gives us the
      statistics of domain sizes during coarsening, can also be used as a strict test
      for this dynamic universality class.

PMID- 19113315
TI  - Complex spontaneous flows and concentration banding in active polar films.
AB  - We study the dynamical properties of active polar liquid crystalline films. Like
      active nematic films, active polar films undergo a dynamical transition to
      spontaneously flowing steady states. Spontaneous flow in polar fluids is,
      however, always accompanied by strong concentration inhomogeneities or "banding"
      not seen in nematics. In addition, a spectacular property unique to polar active
      films is their ability to generate spontaneously oscillating and banded flows
      even at low activity. The oscillatory flows become increasingly complicated for
      strong polarity.

PMID- 19113316
TI  - Dynamics of semiflexible polymer solutions in the highly entangled regime.
AB  - We present experimental evidence that the effective medium approximation (EMA),
      [D. C. Morse, Phys. Rev. E 63, 031502 (2001)], provides the correct scaling law
      of the plateau modulus G0 proportional variantrho4/3Lp(-1/3) (with rho the
      contour length per unit volume and Lp the persistence length) of semiflexible
      polymer solutions, in the highly entangled regime. Competing theories, including
      a binary collision approximation (BCA), instead predict G0 proportional,
      variantrho7/5Lp(-1/5). We have tested both predictions using F-actin solutions
      which permit experimental control of Lp independently of other parameters. A
      combination of video particle tracking microrheology and dynamic light scattering
      yields independent measurements of G0 and Lp, respectively. Thus we can
      distinguish between the two proposed laws, in contrast to previous experimental
      studies focused on the (less discriminating) concentration dependence.

PMID- 19113317
TI  - Reversal of the weak measurement of a quantum state in a superconducting phase
      qubit.
AB  - We demonstrate in a superconducting qubit the conditional recovery (uncollapsing)
      of a quantum state after a partial-collapse measurement. A weak measurement
      extracts information and results in a nonunitary transformation of the qubit
      state. However, by adding a rotation and a second partial measurement with the
      same strength, we erase the extracted information, canceling the effect of both
      measurements. The fidelity of the state recovery is measured using quantum
      process tomography and found to be above 70% for partial-collapse strength less
      than 0.6.

PMID- 19113318
TI  - Dissipation induced coherence of a two-mode Bose-Einstein condensate.
AB  - We discuss the dynamics of a Bose-Einstein condensate in a double-well trap
      subject to phase noise and particle loss. The phase coherence of a weakly
      interacting condensate as well as the response to an external driving show a
      pronounced stochastic resonance effect: Both quantities become maximal for a
      finite value of the dissipation rate matching the intrinsic time scales of the
      system. Even stronger effects are observed when dissipation acts in concurrence
      with strong interparticle interactions, restoring the purity of the condensate
      almost completely and increasing the phase coherence significantly.

PMID- 19113319
TI  - Possibility of prolific pair production with high-power lasers.
AB  - Prolific electron-positron pair production is possible at laser intensities
      approaching 10;{24} W cm;{-2} at a wavelength of 1 mum. An analysis of electron
      trajectories and interactions at the nodes (B=0) of two counterpropagating,
      circularly polarized laser beams shows that a cascade of gamma rays and pairs
      develops. The geometry is generalized qualitatively to linear polarization and
      laser beams incident on a solid target.

PMID- 19113320
TI  - Quantum Zeno and anti-Zeno effects: without the rotating-wave approximation.
AB  - We show that the counterrotating, neglected in the previous studies of the
      quantum Zeno effect (QZE) in atomic decay, can have a large impact on the short
      time evolution. We calculate the electron self-energy, the Lamb shift, and the
      QZE without making the rotating-wave approximation (RWA) and show that, for
      hydrogen in free space, the Zeno time is longer by 2 orders of magnitude than
      that obtained from the RWA. We also show that there is no anti-Zeno effect as the
      counterrotating terms and rotating terms represent the opposite processes in the
      higher frequency region. Consequently, the experimental measurement of the QZE
      may be much easier than what was determined with the RWA results.

PMID- 19113321
TI  - Experimental quantum computing without entanglement.
AB  - Deterministic quantum computation with one pure qubit (DQC1) is an efficient
      model of computation that uses highly mixed states. Unlike pure-state models, its
      power is not derived from the generation of a large amount of entanglement.
      Instead it has been proposed that other nonclassical correlations are responsible
      for the computational speedup, and that these can be captured by the quantum
      discord. In this Letter we implement DQC1 in an all-optical architecture, and
      experimentally observe the generated correlations. We find no entanglement, but
      large amounts of quantum discord-except in three cases where an efficient
      classical simulation is always possible. Our results show that even fully
      separable, highly mixed, states can contain intrinsically quantum mechanical
      correlations and that these could offer a valuable resource for quantum
      information technologies.

PMID- 19113322
TI  - Directional coupling for quantum computing and communication.
AB  - We introduce the concept of directional coupling, i.e., the selective transfer of
      a state between adjacent quantum wires, in the context of quantum computing and
      communication. Our analysis rests upon a mathematical analogy between a dual
      channel directional coupler and a composite spin system.

PMID- 19113323
TI  - Steady state entanglement in the mechanical vibrations of two dielectric
      membranes.
AB  - We consider two dielectric membranes suspended inside a Fabry-Perot cavity, which
      are cooled to a steady state via a drive by suitable classical lasers. We show
      that the vibrations of the membranes can be entangled in this steady state. They
      thus form two mechanical, macroscopic degrees of freedom that share steady state
      entanglement.

PMID- 19113324
TI  - Characterization of collective Gaussian attacks and security of coherent-state
      quantum cryptography.
AB  - We provide a simple description of the most general collective Gaussian attack in
      continuous-variable quantum cryptography. In the scenario of such general
      attacks, we analyze the asymptotic secret-key rates which are achievable with
      coherent states, joint measurements of the quadratures and one-way classical
      communication.

PMID- 19113325
TI  - Heat conductivity from molecular chaos hypothesis in locally confined billiard
      systems.
AB  - We study the transport properties of a large class of locally confined
      Hamiltonian systems, in which neighboring particles interact through hard-core
      elastic collisions. When these collisions become rare and the systems large, we
      derive a Boltzmann-like equation for the evolution of the probability densities.
      We solve this equation in the linear regime and compute the heat conductivity
      from a Green-Kubo formula. The validity of our approach is demonstrated by
      comparing our predictions with the results of numerical simulations performed on
      a new class of high-dimensional defocusing chaotic billiards.

PMID- 19113326
TI  - Quantification of the information limit of transmission electron microscopes.
AB  - The resolving power of high-resolution transmission electron microscopes is
      characterized by the information limit, which reflects the size of the smallest
      object detail observable with a particular instrument. We introduce a highly
      accurate measurement method for the information limit, which is suitable for
      modern aberration-corrected electron microscopes. An experimental comparison with
      the traditionally applied Young's fringe method yields severe discrepancies and
      confirms theoretical considerations according to which the Young's fringe method
      does not reveal the information limit.

PMID- 19113327
TI  - Search for lepton flavor violation in upsilon decays.
AB  - In this Letter, we describe a search for lepton flavor violation (LFV) in the
      bottomonium system. We search for leptonic decays Upsilon(nS)-->mutau (n=1, 2,
      and 3) using the data collected with the CLEO III detector. We identify the tau
      lepton using its leptonic decay nu_{tau}nu[over ]_{e}e and utilize
      multidimensional likelihood fitting with probability density function shapes
      measured from independent data samples. We report our estimates of 95% C.L. upper
      limits on LFV branching fractions of Upsilon mesons. We interpret our results in
      terms of the exclusion plot for the energy scale of a hypothetical new
      interaction versus its effective LFV coupling in the framework of effective field
      theory.

PMID- 19113331
TI  - Color fluctuations in the nucleon in high-energy scattering.
AB  - We study quantum fluctuations of the nucleon's parton densities by combining QCD
      factorization for hard processes with the notion of cross section fluctuations in
      soft diffraction. The fluctuations of the small-x gluon density are related to
      the ratio of inelastic and elastic vector meson production in ep scattering. A
      simple dynamical model explains the HERA data and predicts the x and Q2
      dependence of the ratio. In pp/p[over ]p scattering, fluctuations enhance
      multiple hard processes (but cannot explain the Tevatron CDF data), and reduce
      gap survival in central exclusive diffraction.

PMID- 19113330
TI  - Evidence for a parity doublet Delta(1920)P33 and Delta(1940)D33 from gammap-
      >ppi;{0}eta.
AB  - Evidence is reported for the existence of a parity doublet of Delta resonances
      with total angular momentum J=3/2 from photoproduction of the ppi;{0}eta final
      state. The two parity partners Delta(1920)P33 and Delta(1940)D33 make significant
      contributions to the reaction. Cascades of resonances into Delta(1232)eta,
      N(1535)pi, and Na0(980) are clearly observed.

PMID- 19113332
TI  - Convergence of the chiral expansion in two-flavor lattice QCD.
AB  - We test the convergence property of the chiral perturbation theory using a
      lattice QCD calculation of pion mass and decay constant with two dynamical quark
      flavors. The lattice calculation is performed using the overlap fermion
      formulation, which realizes exact chiral symmetry at finite lattice spacing. By
      comparing various expansion prescriptions, we find that the chiral expansion is
      well saturated at the next-to-leading order for pions lighter than approximately
      450 MeV. Better convergence behavior is found, in particular, for a resummed
      expansion parameter xi, with which the lattice data in the pion mass region 290
      750 MeV can be fitted well with the next-to-next-to-leading order formulas. We
      obtain the results in two-flavor QCD for the low energy constants l[over ]_{3}
      and l[over ]_{4} as well as the pion decay constant, the chiral condensate, and
      the average up and down quark mass.

PMID- 19113333
TI  - First Penning-trap mass measurement of the exotic halo nucleus 11Li.
AB  - In this Letter, we report a new mass for 11Li using the trapping experiment TITAN
      at TRIUMF's ISAC facility. This is by far the shortest-lived nuclide, t_{1/2}=8.8
      ms, for which a mass measurement has ever been performed with a Penning trap.
      Combined with our mass measurements of ;{8,9}Li we derive a new two-neutron
      separation energy of 369.15(65) keV: a factor of 7 more precise than the best
      previous value. This new value is a critical ingredient for the determination of
      the halo charge radius from isotope-shift measurements. We also report results
      from state-of-the-art atomic-physics calculations using the new mass and extract
      a new charge radius for 11Li. This result is a remarkable confluence of nuclear
      and atomic physics.

PMID- 19113334
TI  - Laser channeling of Bethe-Heitler pairs.
AB  - Electron-positron pair creation is analyzed for an arrangement involving three
      external fields: a high-frequency gamma photon, the Coulomb field of a nucleus,
      and a strong laser wave. The frequency of the incoming gamma photon is assumed to
      be larger than the threshold for pair production in the absence of a laser, and
      the peak electric field of the laser is assumed to be much weaker than
      Schwinger's critical field. The total number of pairs produced is found to be
      essentially unchanged by the laser field, while the differential cross section is
      drastically modified. We show that the laser can channel the angular distribution
      of electron-positron pairs into a narrow angular region, which also facilitates
      experimental observation.

PMID- 19113335
TI  - Optical feshbach resonance using the intercombination transition.
AB  - We report control of the scattering wave function by an optical Feshbach
      resonance effect using ytterbium atoms. The narrow intercombination line (1S0
      3P1) is used for efficient control as proposed by Ciurylo et al. [Phys. Rev. A
      71, 030701(R) (2005)10.1103/PhysRevA.71.030701]. The manipulation of the
      scattering wave function is monitored with the change of a photoassociation rate
      caused by another laser. The optical Feshbach resonance is especially efficient
      for isotopes with large negative scattering lengths such as 172Yb, and we have
      confirmed that the scattering phase shift divided by the wave number, which gives
      the scattering length in the zero energy limit, is changed by about 30 nm.

PMID- 19113337
TI  - Molecular beam collisions with a magnetically trapped target.
AB  - Cold, neutral hydroxyl radicals are Stark decelerated and efficiently loaded into
      a permanent magnetic trap. The OH molecules are trapped in the rovibrational
      ground state at a density of approximately 10;{6} cm;{-3} and temperature of 70
      mK. Collision studies between the trapped OH sample and supersonic beams of
      atomic He and molecular D2 determine absolute collision cross sections. The He-OH
      and D2-OH center-of-mass collision energies are tuned from 60 cm;{-1} to 230 cm;{
      1} and 145 cm;{-1} to 510 cm;{-1}, respectively, yielding evidence of quantum
      threshold scattering and resonant energy transfer between colliding particles.

PMID- 19113336
TI  - Collisional stability of a three-component degenerate fermi gas.
AB  - We report on the creation of a degenerate Fermi gas consisting of a balanced
      mixture of atoms in three different hyperfine states of 6Li. This new system
      consists of three distinguishable fermions with different and tunable
      interparticle scattering lengths a_{12}, a_{13}, and a_{23}. We are able to
      prepare samples containing 5x10;{4} atoms in each state at a temperature of about
      215 nK, which corresponds to T/T_{F} approximately 0.37. We investigated the
      collisional stability of the gas for magnetic fields between 0 and 600 G and
      found a prominent loss feature at 130 G. From lifetime measurements, we
      determined three-body loss coefficients, which vary over nearly 3 orders of
      magnitude.

PMID- 19113338
TI  - Explosion of xenon clusters driven by intense femtosecond pulses of extreme
      ultraviolet light.
AB  - The explosions of large xenon clusters irradiated by intense, femtosecond extreme
      ultraviolet pulses at a wavelength of 38 nm have been studied. Using high
      harmonic generation from a 35 fs laser, clusters have been irradiated by extreme
      ultraviolet pulses at intensity approaching 10;{11} W/cm;{2}. Charge states up to
      Xe8+ are observed, states well above those produced by single atom illumination,
      indicating that plasma continuum lowering is important. Furthermore, the kinetic
      energy distribution of the exploding ions is consistent with a quasineutral
      hydrodynamic expansion, rather than a Coulomb explosion.

PMID- 19113339
TI  - Multimodal properties and dynamics of gradient echo quantum memory.
AB  - We investigate the properties of a recently proposed gradient echo memory (GEM)
      scheme for information mapping between optical and atomic systems. We show that
      GEM can be described by the dynamic formation of polaritons in k space. This
      picture highlights the flexibility and robustness with regards to the external
      control of the storage process. Our results also show that, as GEM is a frequency
      encoding memory, it can accurately preserve the shape of signals that have large
      time-bandwidth products, even at moderate optical depths. At higher optical
      depths, we show that GEM is a high fidelity multimode quantum memory.

PMID- 19113340
TI  - Two-photon gateway in one-atom cavity quantum electrodynamics.
AB  - Single atoms absorb and emit light from a resonant laser beam photon by photon.
      We show that a single atom strongly coupled to an optical cavity can absorb and
      emit resonant photons in pairs. The effect is observed in a photon correlation
      experiment on the light transmitted through the cavity. We find that the atom
      cavity system transforms a random stream of input photons into a correlated
      stream of output photons, thereby acting as a two-photon gateway. The phenomenon
      has its origin in the quantum anharmonicity of the energy structure of the atom
      cavity system. Future applications could include the controlled interaction of
      two photons by means of one atom.

PMID- 19113328
TI  - Searches for B meson decays to phiphi, phirho, phif_{0}(980), and
      f_{0}(980)f_{0}(980) final states.
AB  - We present the results of searches for B decays to charmless final states
      involving varphi, f_{0}(980), and charged or neutral rho mesons. The data sample
      corresponds to 384x10;{6} BB[over ] pairs collected with the BABAR detector
      operating at the PEP-II asymmetric-energy e;{+}e;{-} collider at SLAC. We find no
      significant signals and determine the following 90% confidence level upper limits
      on the branching fractions, including systematic uncertainties: B(B;{0}-
      >varphivarphi)<2.0x10;{-7}, B(B;{+}-->varphirho;{+})<30x10;{-7}, B(B;{0}-
      >varphirho;{0})<3.3x10;{-7}, B[B;{0}-->varphif_{0}(980)]xB[f_{0}(980)-
      >pi;{+}pi;{-}]<3.8x10;{-7}, and B[B;{0}-->f_{0}(980)f_{0}(980)]xB[f_{0}(980)-
      >pi;{+}pi;{-}]xB[f_{0}(980)-->K;{+}K;{-}]<2.3x10;{-7}.

PMID- 19113341
TI  - Hiding under the carpet: a new strategy for cloaking.
AB  - A new type of cloak is discussed: one that gives all cloaked objects the
      appearance of a flat conducting sheet. It has the advantage that none of the
      parameters of the cloak is singular and can in fact be made isotropic. It makes
      broadband cloaking in the optical frequencies one step closer.

PMID- 19113342
TI  - Observation of defect-free surface modes in optical waveguide arrays.
AB  - We report on the experimental observation of novel defect-free surface modes
      predicted theoretically for modulated photonic lattices [I. L. Garanovich et al.,
      Phys. Rev. Lett. 100, 203904 (2008)10.1103/PhysRevLett.100.203904]. We generate
      the linear surface modes in truncated arrays of periodically curved optical
      waveguides created in fused silica by a laser direct-writing technique. Our
      results demonstrate that the degree of surface wave localization can be
      controlled by selecting the waveguide bending amplitude.

PMID- 19113343
TI  - Membrane-type acoustic metamaterial with negative dynamic mass.
AB  - We present the experimental realization and theoretical understanding of a
      membrane-type acoustic metamaterial with very simple construct, capable of
      breaking the mass density law of sound attenuation in the 100-1000 Hz regime by a
      significant margin ( approximately 200 times). Owing to the membrane's weak
      elastic moduli, there can be low-frequency oscillation patterns even in a small
      elastic film with fixed boundaries defined by a rigid grid. The vibrational
      eigenfrequencies can be tuned by placing a small mass at the center of the
      membrane sample. Near-total reflection is achieved at a frequency between two
      eigenmodes where the in-plane average of normal displacement is zero. By using
      finite element simulations, negative dynamic mass is explicitly demonstrated at
      frequencies around the total reflection frequency. Excellent agreement between
      theory and experiment is obtained.

PMID- 19113345
TI  - Trapping and destruction of long-range high-intensity optical filaments by
      molecular quantum wakes in air.
AB  - We report the first observation of the strong effect of quantum rotational wave
      packets in atmospheric air on the long-range filamentary propagation of intense
      femtosecond laser pulses. In a pump-probe experiment, we find that the probe
      filament can be sucked into the pump filament's molecular quantum wake and
      trapped or be destroyed by it.

PMID- 19113344
TI  - Universal cone angle of ac electrosprays due to net charge entrainment.
AB  - The half-angle of an ac cone is shown to exhibit a universal (length-scale
      independent) asymptotic value of 12.6 degrees at high-permittivity ratio, which
      is quite distinct from the 49.3 degrees of dc Taylor cones. Our theory and
      experiments suggest that ac entrainment of low-mobility anions, generated by
      field-assisted ion dissociation, sustains a net charge at the ac cone. Mutual
      Coulombic repulsion between these free charges compensates the singular azimuthal
      capillary force and elongates the cone with an axial force that does not exist in
      dc cones.

PMID- 19113346
TI  - Nature of transport across sheared zonal flows in electrostatic ion-temperature
      gradient gyrokinetic plasma turbulence.
AB  - It is shown that the usual picture for the suppression of turbulent transport
      across a stable sheared flow based on a reduction of diffusive transport
      coefficients is, by itself, incomplete. By means of toroidal gyrokinetic
      simulations of electrostatic, collisionless ion-temperature-gradient turbulence,
      it is found that the nature of the transport is altered fundamentally, changing
      from diffusive to anticorrelated and subdiffusive. Additionally, whenever the
      flows are self-consistently driven by turbulence, the transport gains an
      additional non-Gaussian character. These results suggest that a description of
      transport across sheared flows using effective diffusivities is oversimplified.

PMID- 19113347
TI  - Alpha channeling in a rotating plasma.
AB  - The wave-particle alpha-channeling effect is generalized to include rotating
      plasma. Specifically, radio frequency waves can resonate with alpha particles in
      a mirror machine with ExB rotation to diffuse the alpha particles along
      constrained paths in phase space. Of major interest is that the alpha-particle
      energy, in addition to amplifying the rf waves, can directly enhance the rotation
      energy which in turn provides additional plasma confinement in centrifugal fusion
      reactors. An ancillary benefit is the rapid removal of alpha particles, which
      increases the fusion reactivity.

PMID- 19113348
TI  - Magnetic reconnection by a self-retreating X line.
AB  - Particle-in-cell simulations of collisionless magnetic reconnection are performed
      to study asymmetric reconnection in which an outflow is blocked by a hard wall
      while leaving sufficiently large room for the outflow of the opposite direction.
      This condition leads to a slow, roughly constant motion of the diffusion region
      away from the wall, the so-called "X-line retreat." The typical retreat speed is
      approximately 0.1 times the Alfven speed. At the diffusion region, ion flow
      pattern shows strong asymmetry and the ion stagnation point and the X line are
      not collocated. A surprise, however, is that the reconnection rate remains the
      same unaffected by the retreat motion.

PMID- 19113349
TI  - Evolution from a molecular Rydberg gas to an ultracold plasma in a seeded
      supersonic expansion of NO.
AB  - We report the spontaneous formation of a plasma from a gas of cold Rydberg
      molecules. Double-resonant laser excitation promotes nitric oxide, cooled to 1 K
      in a seeded supersonic molecular beam, to single Rydberg states extending as deep
      as 80 cm;{-1} below the lowest ionization threshold. The density of excited
      molecules in the illuminated volume approaches 1x10;{13} cm;{-3}. This population
      evolves to produce free electrons and a durable cold plasma of electrons and
      intact NO+ ions.

PMID- 19113350
TI  - Hydrogen clusters that remain fluid at low temperature.
AB  - Superfluidity of hydrogen, predicted three decades ago, continues to elude
      experimental observation, due to the high freezing temperature of H2 at T=13.8 K.
      Here, large para-H2 clusters are obtained in a cryogenic pulsed free jet
      expansion and are studied via nonlinear Raman spectroscopy. Clusters formed from
      neat pH_{2} are solid as evidenced by the characteristic splitting of the
      rotational S0(0) line. However, clusters formed of highly diluted pH_{2} (< or =
      1%) in He have a single S0(0) line and remain liquid at the estimated superfluid
      transition temperature of T=1-2 K.

PMID- 19113351
TI  - Crack growth by surface diffusion in viscoelastic media.
AB  - We discuss steady state crack growth in the spirit of a free boundary problem. It
      turns out that mode I and mode III situations are very different from each other:
      In particular, mode III exhibits a pronounced transition towards unstable crack
      growth at higher driving forces, and the behavior close to the Griffith point is
      determined entirely through crack surface dissipation, whereas in mode I the
      fracture energy is renormalized due to a remaining finite viscous dissipation.
      Intermediate mixed-mode scenarios allow steady state crack growth with higher
      velocities than for pure mode I.

PMID- 19113329
TI  - Forward-backward asymmetry in top-quark production in pp[over] collisions at
      sqrt[s]=1.96 TeV.
AB  - We present measurements of the forward-backward charge asymmetry in top pair
      production using 1.9 fb;{-1} of pp[over ] collisions at sqrt[s]=1.96 TeV recorded
      with the Collider Detector at Fermilab II. Correcting for acceptance and
      measurement dilutions we obtain parton-level asymmetries of A_{FB};{pp[over
      ]}=0.17+/-0.08 in the pp[over ] frame and A_{FB};{tt[over ]}=0.24+/-0.14 in the
      tt[over ] frame. The values are consistent with the standard model expectation
      and disfavor exotic production mechanisms with significant negative values.

PMID- 19113352
TI  - Local structural origins of the distinct electronic properties of Nb-substituted
      SrTiO3 and BaTiO3.
AB  - The perovskite SrTiO3 becomes metallic with 0.03% to 0.1% Nb substitution on the
      Ti site, while BaTiO3 remains insulating above 10% Nb substitution. Given the
      nearly identical structure and electron counts of the two materials, the distinct
      ground states for low substitution have been a long-standing puzzle. Here we find
      from neutron studies of average and local structure the subtle yet critical
      difference that we believe underpins the distinct electronic properties in these
      fascinating materials. While SrTi0.875Nb0.125O3 possesses a distorted noncubic
      structure at 15 K, (Nb/Ti)O6 octahedra in the structure are regular.
      BaTi0.875Nb0.125O3, on the other hand, shows evidence for local cation off
      centering while retaining a cubic structure.

PMID- 19113353
TI  - Role of macroscopic deformations in energetics of vacancies in aluminum.
AB  - Electronic structure calculations on million-atom samples are employed to
      investigate the effect of macroscopic deformations on energetics of vacancies in
      aluminum. We find that volumetric strain associated with a deformation largely
      governs the formation energies of monovacancies and divacancies. The calculations
      suggest that nucleation of these defects is increasingly favorable under
      volumetric expansion, so much to the point that they become thermodynamically
      favorable under large positive volumetric strains. On the contrary, on an
      average, existing vacancies are found to bind preferentially under compressive
      volumetric strains. Shear deformations did not affect the formation energies of
      vacancies, but strongly influenced the 110 divacancy binding energies, causing
      them to orient under energetically preferential directions.

PMID- 19113354
TI  - Divergent four-point dynamic density correlation function of a glassy suspension.
AB  - We use a recently derived diagrammatic formulation of the dynamics of interacting
      Brownian particles [G. Szamel, J. Chem. Phys. 127, 084515
      (2007)10.1063/1.2759487] to study a four-point dynamic density correlation
      function. We resum a class of diagrams which separate into two disconnected
      components upon cutting a single propagator. The resulting formula for the four
      point correlation function can be expressed in terms of three-point functions
      closely related to the three-point susceptibility introduced by Biroli et al.
      [Phys. Rev. Lett. 97, 195701 (2006)10.1103/PhysRevLett.97.195701] and the
      standard two-point correlation function. The four-point function has a structure
      very similar to that proposed by Berthier and collaborators [Science 310, 1797
      (2005)10.1126/science.1120714; J. Chem. Phys. 126, 184503
      (2007)10.1063/1.2721554]. It exhibits a small wave vector divergence at the mode
      coupling transition.

PMID- 19113355
TI  - Universal distributions generated in a nucleation pulse.
AB  - Asymptotic analysis of the nucleation-growth equations describing a nucleation
      pulse of arbitrary duration is performed. It is discovered that after extended
      growth an asymptotic distribution is established, which is not of any standard
      form (Gauss, log-normal, etc.). Regardless of the mass exchange mechanism between
      the nucleus and the metastable phase, in the extremes of long and short pulses
      the shapes of the distribution become universal, with additional insensitivity of
      either the maximum or, respectively, the width to the duration of the pulse.

PMID- 19113356
TI  - Local lattice distortion in the giant negative thermal expansion material Mn3Cu1
      xGexN.
AB  - Giant negative thermal expansion is achieved in antiperovskite manganese nitrides
      when the sharp volume change associated with magnetic ordering is broadened by
      substitution. In this Letter, we address the unique role of the ''magic" element,
      Ge, for such broadening in Mn3Cu1-xGexN. We present evidence for a local lattice
      distortion well described by the low-temperature tetragonal (T4) structure of
      Mn3GeN for a range of x, where the overall structure remains cubic. This
      structural instability shows a strong correlation with the broadness of the
      growth of the ordered magnetic moment and, hence, is considered to trigger the
      broadening of the volume change.

PMID- 19113357
TI  - Monodisperse microisland formation on Ni/Ru(0001) monolayers.
AB  - The creation of identical microislands consisting of Ni trimers and multiples
      thereof on Ru(0001) induced by oxygen adsorption has been observed using scanning
      tunnelling microscopy. The island formation is caused by an oxygen induced
      expulsion of Ni atoms or trimers out of the moire-distorted (densified) Ni
      monolayer. The exceptional stability of the Ni trimers is attributed to oxygen
      attachment, forming Ni-oxygen composites, as verified by detailed density
      functional theory calculations. The high density, identical structure, and
      notable thermal stability of these islands open up new perspectives for the study
      of the properties of nanostructured surfaces.

PMID- 19113358
TI  - Large surface charge density oscillations induced by subsurface phonon
      resonances.
AB  - A density functional perturbation theory study of Cu(111) surface dynamics and
      phonon-induced surface charge density (SCD) oscillations shows that the
      subsurface phonon resonances such as S3, first predicted by embedded-atom
      methods, trigger large SCD charge-density oscillations, thus explaining the large
      helium atom scattering intensity from the anomalous longitudinal resonance found
      in most metal surfaces. The strong coupling between certain phonons and SCD
      oscillations is shown to have implications in inelastic electron tunneling
      spectroscopy and other manifestations of electron-phonon interactions at metal
      surfaces.

PMID- 19113359
TI  - Local density of states for individual energy levels in finite quantum wires.
AB  - The local density of states in finite quantum wires is calculated as a function
      of discrete energies and position along the wire. By using a combination of
      numerical density matrix renormalization group calculations and analytical
      bosonization techniques, it is possible to obtain a good understanding of the
      local spectral weights along the wire in terms of the underlying many-body
      excitations.

PMID- 19113360
TI  - Time-dependent current-density-functional theory of spin-charge separation and
      spin drag in one-dimensional ultracold Fermi gases.
AB  - Motivated by the large interest in the nonequilibrium dynamics of low-dimensional
      quantum many-body systems, we present a fully microscopic theoretical and
      numerical study of the charge and spin dynamics in a one-dimensional ultracold
      Fermi gas following a quench. Our approach, which is based on time-dependent
      current-density-functional theory, is applicable well beyond the linear-response
      regime and produces both spin-charge separation and spin-drag-induced broadening
      of the spin packets.

PMID- 19113361
TI  - Optical probe of carrier doping by X-ray irradiation in the organic dimer Mott
      insulator kappa-(BEDT-TTF)_{2}Cu[N(CN)_{2}]Cl.
AB  - We investigated the infrared optical spectra of an organic dimer Mott insulator
      kappa-(BEDT-TTF)_{2}Cu[N(CN)_{2}]Cl, which was irradiated with x rays. We
      observed that the irradiation caused a large spectral weight transfer from the
      midinfrared region, where interband transitions in the dimer and Mott-Hubbard
      bands take place, to a Drude part in a low-energy region; this caused the Mott
      gap to collapse. The increase of the Drude part indicates a carrier doping into
      the Mott insulator due to irradiation defects. The strong redistribution of the
      spectral weight demonstrates that the organic Mott insulator is very close to the
      phase border of the bandwidth-controlled Mott-insulator-metal transition.

PMID- 19113362
TI  - Pairing symmetry in a two-orbital exchange coupling model of oxypnictides.
AB  - We study the pairing symmetry of a two-orbital J1-J2 model for FeAs layers in
      oxypnictides. We show that the mixture of an intraorbital unconventional
      s_{x;{2}y;{2}} approximately cos(k_{x})cos(k_{y}) pairing symmetry, which changes
      sign between the electron and hole Fermi surfaces, and a very small d_{x;{2}
      y;{2}} approximately cos(k_{x})-cos(k_{y}) component is favored in a large part
      of the J1-J2 phase diagram. A pure s_{x;{2}y;{2}} pairing state is favored for
      J2>J1. The signs of the d_{x;{2}-y;{2}} order parameters in the two different
      orbitals are opposite. While a small d_{xy} approximately sin(k_{x})sin(k_{y})
      interorbital pairing coexists in the above phases, the intraorbital d_{xy}
      pairing is not favored even for large J2.

PMID- 19113363
TI  - Possible anisotropic s--f hybridization in a cubic heavy-fermion compound:
      CeIn1Sn2.
AB  - Polarized neutron scattering measurements on a single crystal of composition
      CeIn1Sn2 show a broad, single-ion, spectral response centered on a characteristic
      energy of approximately 9+/-1 meV at the zone boundary point (0 0 1.5). The zone
      center spectral response is closely similar in form but has a slightly reduced
      amplitude, smaller by some 20%. Constant-omega scans show that these intensity
      modulations, of amplitude approximately 10%, resembling intersite
      antiferromagnetic correlations, are superimposed on a mean variation that follows
      the Ce3+, 4f;{1}, single-ion form factor, and are tentatively attributed to q
      dependent hybridization of the localized 4f state with the conduction electrons.

PMID- 19113364
TI  - Spin noise spectroscopy in GaAs (110) quantum wells: access to intrinsic spin
      lifetimes and equilibrium electron dynamics.
AB  - In this Letter, the first spin noise spectroscopy measurements in semiconductor
      systems of reduced effective dimensionality are reported. The nondemolition
      measurement technique gives access to the otherwise concealed intrinsic, low
      temperature electron spin relaxation time of n-doped GaAs (110) quantum wells and
      to the corresponding low temperature anisotropic spin relaxation. The Brownian
      motion of the electrons within the spin noise probe laser spot becomes manifest
      in a modification of the spin noise line width. Thereby, the spatially resolved
      observation of the stochastic spin polarization uniquely allows to study electron
      dynamics at equilibrium conditions with a vanishing total momentum of the
      electron system.

PMID- 19113365
TI  - Primary tunnel junction thermometry.
AB  - We describe the concept and experimental demonstration of primary thermometry
      based on a four-probe measurement of a single tunnel junction embedded within
      four arrays of junctions. We show that in this configuration random sample
      specific and environment-related errors can be avoided. This method relates
      temperature directly to Boltzmann constant, which will form the basis of the
      definition of temperature and realization of official temperature scales in the
      future.

PMID- 19113366
TI  - Quasiparticle chirality in epitaxial graphene probed at the nanometer scale.
AB  - Graphene exhibits unconventional two-dimensional electronic properties resulting
      from the symmetry of its quasiparticles, which leads to the concepts of
      pseudospin and electronic chirality. Here, we report that scanning tunneling
      microscopy can be used to probe these unique symmetry properties at the nanometer
      scale. They are reflected in the quantum interference pattern resulting from
      elastic scattering off impurities, and they can be directly read from its fast
      Fourier transform. Our data, complemented by theoretical calculations,
      demonstrate that the pseudospin and the electronic chirality in epitaxial
      graphene on SiC(0001) correspond to the ones predicted for ideal graphene.

PMID- 19113367
TI  - Formulation of time-resolved counting statistics based on a positive-operator
      valued measure.
AB  - We propose a derivation of the full counting statistics of electronic current
      based on a positive-operator-valued measure. Our approach justifies the Levitov
      Lesovik formula in the long-time limit, but can be generalized to the detection
      of finite-frequency noise correlations. The combined action of the projection
      postulate and the quantum formula for current noise at high frequencies imply an
      additional white noise. Estimates for this additional noise are in accordance
      with known experiments. We propose an experimental test of our conjecture by a
      simultaneous measurement of high- and low-frequency noise.

PMID- 19113368
TI  - Inherent stochasticity of superconductor-resistor switching behavior in
      nanowires.
AB  - We study the stochastic dynamics of superconductive-resistive switching in
      hysteretic current-biased superconducting nanowires undergoing phase-slip
      fluctuations. We evaluate the mean switching time using the master-equation
      formalism, and hence obtain the distribution of switching currents. We find that
      as the temperature is reduced this distribution initially broadens; only at lower
      temperatures does it show the narrowing with cooling naively expected for phase
      slips that are thermally activated. We also find that although several phase-slip
      events are generally necessary to induce switching, there is an experimentally
      accessible regime of temperatures and currents for which just one single phase
      slip event is sufficient to induce switching, via the local heating it causes.

PMID- 19113369
TI  - Coexistence of competing orders with two energy gaps in real and momentum space
      in the high temperature superconductor Bi_{2}Sr_{2-x}La_{x}CuO_{6+delta}.
AB  - Through a combined scanning tunneling microscopy and angle-resolved photoemission
      spectroscopy study, we report the observation of two distinct gaps (a small and a
      large gap) that coexist both in real space and in the antinodal region of
      momentum space, below the superconducting transition temperature (T_{c}) of
      Bi_{2}Sr_{2-x}La_{x}CuO_{6+delta}. We show that the small gap is associated with
      superconductivity. The large-gap persists above T_{c}, and seems linked to
      observed charge ordering. We find a strong correlation between the large and
      small gaps suggesting that they are affected by similar physical processes.

PMID- 19113370
TI  - Mesoscopic competition of superconductivity and ferromagnetism: conductance peak
      statistics for metallic grains.
AB  - We investigate the competition between superconductivity and ferromagnetism in
      chaotic ultrasmall metallic grains in a regime where both phases can coexist. We
      use an effective Hamiltonian that combines a BCS-like pairing term and a
      ferromagnetic Stoner-like spin exchange term. We study the transport properties
      of the grain in the Coulomb-blockade regime and identify signatures of the
      coexistence of pairing and exchange correlations in the mesoscopic fluctuations
      of the conductance peak spacings and peak heights.

PMID- 19113371
TI  - Superconducting state in SrFe2-xCoxAs2 by internal doping of the iron arsenide
      layers.
AB  - In the strontium iron-cobalt arsenides SrFe2-xCoxAs2 (0.2 < or = x < or = 0.4)
      superconductivity with T_{c} up to 20 K is observed in magnetic susceptibility,
      electrical resistivity, and specific heat data. This first observation of bulk
      superconductivity induced by electron doping in this family of compounds-despite
      strong disorder in the Fe-As layer-favors an itinerant electronic theory in
      contrast to the strongly correlated cuprates and renders a p- or d-wave pairing
      unlikely. The magnetic ordering present in SrFe2As2 is rapidly suppressed by
      substitution of Fe by Co. Density functional theory calculations show that this
      is due to a rigid downshift of the Fe-3d_{x;{2}-y;{2}}-related band edge in the
      density of states.

PMID- 19113372
TI  - Longitudinal spin density wave order in a quasi-1D Ising-like quantum
      antiferromagnet.
AB  - From neutron diffraction measurements on a quasi-1D Ising-like Co2+ spin compound
      BaCo2V2O8, we observed an appearance of a novel type of incommensurate ordering
      in magnetic fields. This ordering is essentially different from the Neel-type
      ordering, which is expected for the classical system, and the peculiar spin
      structure is caused by quantum fluctuation inherent in the quantum spin chain. A
      Tomonaga-Luttinger liquid nature characteristic of the gapless quantum 1D system
      is responsible for the realization of the incommensurate ordering.

PMID- 19113373
TI  - Piezomagnetic quantum dots.
AB  - We study the influence of deformations on magnetic ordering in quantum dots doped
      with magnetic impurities. The reduction of symmetry and the associated
      deformation from circular to elliptical quantum confinement lead to the formation
      of piezomagnetic quantum dots. The strength of elliptical deformation can be
      controlled by the gate voltage to change the magnitude of magnetization, at a
      fixed number of carriers and in the absence of an applied magnetic field. We
      reveal a reentrant magnetic ordering with the increase of elliptical deformation
      and suggest that the piezomagnetic quantum dots can be used as nanoscale magnetic
      switches.

PMID- 19113374
TI  - Dynamical pinning of a domain wall in a magnetic nanowire induced by Walker
      breakdown.
AB  - Transmission probability of a domain wall through a magnetic nanowire is
      investigated as a function of the external magnetic field. A very intriguing
      phenomenon is found that the transmission probability shows a significant drop
      after exceeding the threshold driving field, which contradicts our intuition that
      a domain wall is more mobile in the higher magnetic field. The micromagnetics
      simulation reveals that the domain wall motion in the wire with finite roughness
      causes the dynamical pinning due to the Walker breakdown, which
      semiquantitatively explains our experimental results.

PMID- 19113375
TI  - Spin dependent impurity effects on the 2D frustrated magnetism of NiGa2S4.
AB  - Impurity effects on the triangular antiferromagnets Ni1-xMxGa2S4 (M=Mn, Fe, Co
      and Zn) are studied. The 2D frozen spin-disordered state of NiGa2S4 is stable
      against the substitution of Zn2+ (S=0) and Heisenberg Fe2+ (S=2) spins, and
      exhibits a T2-dependent magnetic specific heat, scaled by the Weiss temperature.
      In contrast, the substitutions with Co2+ (S=3/2) spin with Ising-like anisotropy
      and Heisenberg Mn2+ (S=5/2) spin induce a conventional spin glass phase below 1
      K. From these comparisons, it is suggested that the integer size of the
      Heisenberg spins is important to stabilize the 2D coherent behavior observed in
      the frozen spin-disordered state.

PMID- 19113376
TI  - Control of the magnetoelectric domain-wall stability by a magnetic field in a
      multiferroic MnWO4.
AB  - The relation between the orientation of the magnetic field and the flopped
      ferroelectric polarization has been investigated for multiferroic MnWO4. The
      ferroelectric single-domain state is retained across the polarization flop
      process when the direction of the applied magnetic field slightly deviates from
      the b axis within the ab plane. Furthermore, the electric polarization in the
      high-field P parallela phase is reversed when the P parallelb-to-P parallela
      transition takes place while decreasing and increasing the magnetic fields
      oppositely canted from the b axis. These results indicate that the symmetry
      breaking induced by a canted magnetic field determines the direction of the
      polarization flop, which corresponds to the direction of the vector spin
      chirality. The stability of the magnetoelectric domain walls in a canted magnetic
      field play a key role in the directional control of the electric polarization
      flop phenomenon.

PMID- 19113377
TI  - Microscopic understanding of negative magnetization in Cu, Mn, and Fe based
      Prussian blue analogues.
AB  - A crossover of the field-cooled magnetization from positive to negative has been
      observed below the magnetic ordering temperature (17.9 K) in a multimetal
      Prussian Blue analogue (PBA), Cu_{0.73}Mn_{0.77}[Fe(CN)_{6}].zH_{2}O. The reverse
      Monte Carlo (RMC) modeling (using the program RMCPOW) has been used to derive the
      various scattering contributions (e.g., nuclear diffuse, nuclear Bragg, magnetic
      diffuse, and magnetic Bragg) from the observed neutron diffraction patterns. The
      RMC analysis combined with the Rietveld refinement technique show an
      antiferromagnetic ordering of Mn moments with respect to the Cu as well as the Fe
      moments. Our study gives the first neutron magnetic structure evidence towards
      the microscopic understanding of the negative magnetization in the PBAs. This
      information can be effectively utilized to design suitable PBAs for making
      multifunctional devices.

PMID- 19113378
TI  - Evidence of a transition from nonlinear to linear screening of a two-dimensional
      electron system detected by photoluminescence spectroscopy.
AB  - We clearly identify single-electron-localization (SEL), nonlinear screening
      (NLS), and linear screening (LS) regimes of gate induced electrons in a GaAs
      quantum well from photoluminescence spectra and intergate capacitance. Neutral
      and charged excitons observed in the SEL regime rapidly lose their oscillator
      strength when electron puddles are formed, which mark the onset of NLS. A further
      increase in the density of the electrons induces the transition from the NLS to
      LS, where the emission of a charged exciton changes to the recombination of two
      dimensional electron gas and a hole.

PMID- 19113379
TI  - Multipulse operation and optical detection of nuclear spin coherence in a
      GaAs/AlGaAs quantum well.
AB  - We demonstrate manipulation of nuclear spin coherence in a GaAs/AlGaAs quantum
      well by optically detected nuclear magnetic resonance (NMR). A phase shift of the
      Larmor precession of photoexcited electron spins is detected to read out the
      hyperfine-coupled nuclear spin polarization. Multipulse NMR sequences are
      generated to control the population and examine the phase coherence in
      quadrupolar-split spin-3/2 75As nuclei. The phase coherence among the multilevel
      nuclear spin states is addressed by application of pulse sequences that are used
      in quantum gate operations.

PMID- 19113380
TI  - Long-lived spin coherence in silicon with an electrical spin trap readout.
AB  - Pulsed electrically detected magnetic resonance of phosphorous (31P) in bulk
      crystalline silicon at very high magnetic fields (B0>8.5 T) and low temperatures
      (T=2.8 K) is presented. We find that the spin-dependent capture and reemission of
      highly polarized (>95%) conduction electrons by equally highly polarized 31P
      donor electrons introduces less decoherence than other mechanisms for spin-to
      charge conversion. This allows the electrical detection of spin coherence times
      in excess of 100 mus, 50 times longer than the previous maximum for electrically
      detected spin readout experiments.

PMID- 19113381
TI  - Advillin folding takes place on a hypersurface of small dimensionality.
AB  - All-atom explicit-solvent molecular dynamics simulations have been used to
      investigate the topological structure of the space explored during folding by the
      c-terminal fragment of the Advillin headpiece, a 36 amino-acid protein. A fractal
      dimension analysis shows that the hypersurface explored during the folding
      process has an approximate dimensionality of only three. It is shown that this
      low dimensionality persists well above the unfolding temperature and is not
      present in simple coarse-grained models.

PMID- 19113382
TI  - Spindles, cusps, and bifurcation for capsules in Stokes flow.
AB  - Interfacial dynamics of membrane-enclosed fluid volumes in viscous flows is
      complicated due to the coupling of the fluid dynamics with the membrane
      properties. Based on computational investigation via our interfacial spectral
      boundary element algorithm, our study shows that a (strain-hardening) Skalak-type
      capsule in a planar extensional Stokes flow develops steady-state shapes whose
      edges from spindled become cusped with increasing flow rate owing to a transition
      of the edge tensions from tensile to compressive. A bifurcation in the steady
      state shapes is also found (i.e., existence of both spindled and cusped edges for
      a range of high flow rates) by implementing different transient processes, owing
      to the different evolution of the membrane tensions.

PMID- 19113384
TI  - Critical Casimir forces in colloidal suspensions on chemically patterned
      surfaces.
AB  - We investigate the behavior of colloidal particles immersed in a binary liquid
      mixture of water and 2,6-lutidine in the presence of a chemically patterned
      substrate. Close to the critical point of the mixture, the particles are
      subjected to critical Casimir interactions with force components normal and
      parallel to the surface. Because the strength and sign of these interactions can
      be tuned by variations in the surface properties and the mixtures temperature,
      critical Casimir forces allow the formation of highly ordered monolayers but also
      extend the use of colloids as model systems.

PMID- 19113385
TI  - Filament-induced surface spiral turbulence in three-dimensional excitable media.
AB  - Filament-induced surface defect-mediated turbulence in bounded three-dimensional
      (3D) excitable media is investigated in the regime of negative line tension. In
      this regime turbulence arises due to unstable filaments associated with scroll
      waves and is purely a 3D phenomenon. It is shown that the statistical properties
      of the turbulent defect dynamics can be used to distinguish surface defect
      mediated turbulence from its 2D analog. Mechanisms for the creation and
      annihilation of surface defects are discussed and Markov rate equations are
      employed to model the results.

PMID- 19113383
TI  - Dynamics of specific vesicle-substrate adhesion: from local events to global
      dynamics.
AB  - We present a synergistic combination of simulations and experimental data on the
      dynamics of membrane adhesion. We show that a change in either the density or the
      strength of the bonds results in very different dynamics. Such behavior is
      explained by introducing an effective binding affinity that emerges as a result
      of the competition between the strength of the chemical bonds and the environment
      defined by the fluctuating membrane.

PMID- 19113386
TI  - Laser field alignment of organic molecules on semiconductor surfaces: toward
      ultrafast molecular switches.
AB  - An ultrafast, nanoscale molecular switch is proposed, based on extension of the
      concept of nonadiabatic alignment to surface-adsorbed molecules. The switch
      consists of a conjugated organic molecule adsorbed onto a semiconducting surface
      and placed near a scanning tunneling microscope tip. A low-frequency, polarized
      laser field is used to switch the system by orienting the molecule with the field
      polarization axis, enabling conductance through the junction. Enhancement and
      spatial localization of the incident field by the metallic tip allow operation at
      low intensities. The principles of nonadiabatic alignment lead to switch on and
      off time scales far below rotational time scales.

PMID- 19113387
TI  - Dewetting of a stratified two-component liquid film on a solid substrate.
AB  - Dissipative particle dynamics simulations for the dewetting of a stratified thin
      film, composed of two immiscible fluids of different viscosity, reveal a
      nontrivial dewetting kinetics depending on the location of the more viscous
      liquid with respect to the solid substrate. Our simulations show that when the
      layer of higher viscosity is in contact with the substrate, the energy loss
      through viscous dissipation is concentrated near the contact line. The kinetics
      of dewetting is then inversely proportional to the viscosity of the lower layer
      eta_{A} (with respect to eta_{B} for the upper layer). However, when the liquid
      of higher viscosity is on the upper layer, a new dynamics appears with a
      dewetting velocity V approximately eta_{B};{-0.44}eta_{A};{-0.56}. The difference
      between these two scenarios lies in the different routes through which the
      interfacial energy is converted into heat by viscous dissipation in the rim.

PMID- 19113388
TI  - Attractions between like-charged surfaces with dumbbell-shaped counterions.
AB  - We study the effect of dumbbell-like counterions on the interactions between
      similarly charged surfaces. Via a systematic study using Monte Carlo simulations
      and field theory, we fully consider electrostatic correlations and ion structure
      and find that their intricate coupling determines the equilibrium phase
      behaviors. In particular, an energetic bridging mechanism is revealed to cause
      surface attractions for a finite range of surface separations, even in the
      Poisson-Boltzmann limit.

PMID- 19113389
TI  - Comment on "experimental demonstration of a quantum protocol for Byzantine
      agreement and liar detection".

PMID- 19113391
TI  - Comment on "quantum bounce and cosmic recall".

PMID- 19113393
TI  - Essay: the origin of physical review letters.
AB  - When Sam Goudsmit, then Editor of Physical Review, decided to publish the Letters
      separately, he asked me to become Assistant Editor of the new journal. I wound up
      staying at PRL for a quarter of a century. I describe some of the new techniques
      we developed to speed up review and production so that Letters could be quickly
      published.

PMID- 19113394
TI  - Experimentally testable state-independent quantum contextuality.
AB  - We show that there are Bell-type inequalities for noncontextual theories that are
      violated by any quantum state. One of these inequalities between the correlations
      of compatible measurements is particularly suitable for testing this state
      independent violation in an experiment.

PMID- 19113395
TI  - Stability of dark solitons in three dimensional dipolar Bose-Einstein
      condensates.
AB  - The dynamical stability of dark solitons in dipolar Bose-Einstein condensates is
      studied. For standard short-range interacting condensates, dark solitons are
      unstable against transverse excitations in two and three dimensions. On the
      contrary, due to its nonlocal character, the dipolar interaction allows for
      stable 3D stationary dark solitons, opening a qualitatively novel scenario in
      nonlinear atom optics. We discuss in detail the conditions to achieve this
      stability, which demand the use of an additional optical lattice, and the
      stability regimes.

PMID- 19113396
TI  - Trapping and cooling fermionic atoms into Mott and Neel states.
AB  - We perform a theoretical study of a fermionic gas with two hyperfine states
      confined to an optical lattice. We derive a generic state diagram as a function
      of interaction strength, particle number, and confining potential. We discuss the
      central density, the double occupancy, and their derivatives as probes for the
      Mott state, connecting our findings to the recent experiment of Jordens et al.
      [Nature (London) 455, 204 (2008)10.1038/nature07244]. Using entropic arguments we
      compare two different strategies to reach the antiferromagnetic state in the
      presence of a trapping potential.

PMID- 19113397
TI  - Demonstration of near-optimal discrimination of optical coherent states.
AB  - The optimal discrimination of nonorthogonal quantum states with minimum error
      probability is a fundamental task in quantum measurement theory as well as an
      important primitive in optical communication. In this work, we propose and
      experimentally realize a new and simple quantum measurement strategy capable of
      discriminating two coherent states with smaller error probabilities than can be
      obtained using the standard measurement devices: the Kennedy receiver and the
      homodyne receiver.

PMID- 19113398
TI  - Equivalence of the fractional Fokker-Planck and subordinated Langevin equations:
      the case of a time-dependent force.
AB  - A century after the celebrated Langevin paper [C.R. Seances Acad. Sci. 146, 530
      (1908)] we study a Langevin-type approach to subdiffusion in the presence of time
      dependent force fields. Using a subordination technique, we construct rigorously
      a stochastic Langevin process, whose probability density function is equal to the
      solution of the fractional Fokker-Planck equation with a time-dependent force.
      Our model provides physical insight into the nature of the corresponding process
      through the simulated trajectories. Moreover, the subordinated Langevin equation
      allows us to study subdiffusive dynamics both analytically and numerically via
      Monte Carlo methods.

PMID- 19113399
TI  - Efficient Monte Carlo algorithm in quasi-one-dimensional Ising spin systems.
AB  - We develop an efficient Monte Carlo algorithm, which accelerates slow Monte Carlo
      dynamics in quasi-one-dimensional Ising spin systems. The loop algorithm of the
      quantum Monte Carlo method is applied to the classical spin models with highly
      anisotropic exchange interactions. Both correlation time and real CPU time are
      reduced drastically. The algorithm is demonstrated in the layered triangular
      lattice antiferromagnetic Ising model. We have obtained the relation between the
      transition temperature and the exchange interaction parameters, which modifies
      the result of the chain-mean-field theory.

PMID- 19113400
TI  - The Poisson bracket on free null initial data for gravity.
AB  - Free initial data for general relativity on a pair of intersecting null
      hypersurfaces are well known, but the lack of Poisson brackets and concerns about
      caustics have stymied the development of a constraint free canonical theory. Here
      it is pointed out how caustics and generator crossings can be neatly avoided and
      Poisson brackets on free data are given. On sufficiently regular functions of the
      solution spacetime geometry these brackets match the Poisson brackets defined on
      such functions by the Hilbert action via Peierls' prescription. The symplectic 2
      form is also given in terms of free data.

PMID- 19113402
TI  - Gravitational waves from fragmentation of a primordial scalar condensate into Q
      balls.
AB  - A generic consequence of supersymmetry is the formation of a scalar condensate
      along the flat directions of the potential at the end of cosmological inflation.
      This condensate is usually unstable, and it can fragment into nontopological
      solitons, Q balls. The gravitational waves produced by the fragmentation can be
      detected by the Laser Interferometer Space Antenna, Advanced Laser Interferometer
      Gravitational-Wave Observatory, and Big Bang Observer, which can open an
      important window to the early Universe and the physics at some very high energy
      scales.

PMID- 19113404
TI  - Beta-delayed deuteron emission from (11)Li: decay of the halo.
AB  - The deuteron-emission channel in the beta decay of the halo nucleus (11)Li was
      measured at the Isotope Separator and Accelerator facility at TRIUMF by
      implanting postaccelerated (11)Li ions into a segmented silicon detector. The
      events of interest were identified by correlating the decays of (11)Li with those
      of the daughter nuclei. This method allowed the energy spectrum of the emitted
      deuterons to be extracted, free from contributions from other channels, and a
      precise value for the branching ratio B(d)=1.30(13)x10(-4) to be deduced for
      E(c.m.)>200 keV. The results provide the first unambiguous experimental evidence
      that the decay takes place essentially in the halo of (11)Li and that it proceeds
      mainly to the (9)Li+d continuum, opening up a new means to study the halo wave
      function of (11)Li.

PMID- 19113405
TI  - Precision measurement of the hyperfine structure of laser-cooled radioactive 7Be+
      ions produced by projectile fragmentation.
AB  - The ground state hyperfine splitting of (7)Be+ has been measured by laser
      microwave double-resonance spectroscopy in the online rf trap of RIKEN's slow RI
      beam facility. Be ions produced by projectile fragmentation of 13C at
      approximately 1 GeV were thermalized in a rf ion guide gas cell and subsequently
      laser cooled in the ion trap to approximately 1 microeV. This 10(15)-fold
      reduction of the kinetic energy allows precision spectroscopy of these ions. A
      magnetic hfs constant of A=-742.772 28(43) MHz was measured for 7Be+, from which
      a nuclear magnetic moment of mu(I)=-1.399 28(2)mu(N) was deduced.

PMID- 19113406
TI  - Decay pattern of pygmy states observed in neutron-rich 26Ne.
AB  - Coulomb excitation of the exotic neutron-rich nucleus (26)Ne on a (208)Pb target
      was measured at 58 MeV/u in order to search for low-lying E1 strength above the
      neutron emission threshold. This radioactive beam experiment was carried out at
      the RIKEN Accelerator Research Facility. Using the invariant mass method in the
      25Ne+n channel, we observe a sizable amount of E1 strength between 6 and 10 MeV
      excitation energy. By performing a multipole decomposition of the differential
      cross section, a reduced dipole transition probability of B(E1)=0.49+/-0.16e(2)
      fm(2) is deduced, corresponding to 4.9+/-1.6% of the Thomas-Reiche-Kuhn sum rule.
      For the first time, the decay pattern of low-lying strength in a neutron-rich
      nucleus is measured. The extracted decay pattern is not consistent with several
      mean-field theory descriptions of the pygmy states.

PMID- 19113407
TI  - Paul trapping of radioactive 6He+ ions and direct observation of their beta
      decay.
AB  - We demonstrate that abundant quantities of short-lived beta unstable ions can be
      trapped in a novel transparent Paul trap and that their decay products can
      directly be detected in coincidence. Low energy 6He+ (807 ms half-life) ions were
      extracted from the SPIRAL source at GANIL, then decelerated, cooled, and bunched
      by means of the buffer gas cooling technique. More than 10(8) ions have been
      stored over a measuring period of six days, and about 10(5) decay coincidences
      between the beta particles and the 6Li++ recoiling ions have been recorded. The
      technique can be extended to other short-lived species, opening new possibilities
      for trap assisted decay experiments.

PMID- 19113408
TI  - Absorption enhancement and conformational control of peptides by small silver
      clusters.
AB  - We explored experimentally and theoretically the optical properties of isolated
      silver trimer-dipeptide bioconjugates. The metallic moiety induces a strong
      enhancement of the optical absorption of the peptide. We also show that its
      binding to a peptide can reduce the conformational flexibility and induce
      transitions between secondary structures.

PMID- 19113409
TI  - Strong-field modulated diffraction effects in the correlated electron-nuclear
      motion in dissociating H(2+).
AB  - We show that the electronic dynamics in a molecule driven by a strong field is
      complex and potentially even counterintuitive. As a prototype example, we
      simulate the interaction of a dissociating H2+ molecule with an intense infrared
      laser pulse. Depending on the laser intensity, the direction of the electron's
      motion between the two nuclei is found to follow or oppose the classical laser
      electric force. We explain the sensitive dependence of the correlated electronic
      nuclear motion in terms of the diffracting electronic momentum distribution of
      the dissociating two-center system. The distribution is dynamically modulated by
      the nuclear motion and periodically shifted in the oscillating infrared electric
      field.

PMID- 19113410
TI  - Coherent control of the effective susceptibility through wave mixing in a
      duplicated two-level system.
AB  - We theoretically demonstrate the coherent control of the effective susceptibility
      of a duplicated two-level system. The control is obtained for a linearly
      polarized weak field in the presence of a much stronger orthogonally polarized
      field. For small optical depths, the effective susceptibility chi(eff) behaves as
      chilin(e 2iphi) (chilin) is the linear susceptibility, phi the phase shift)
      allowing coherent control of the optical response. For large optical depths,
      chi(eff) approximately chi(lin), turning an absorber into an amplifier without
      affecting the dispersion.

PMID- 19113411
TI  - Temporal self-restoration of compressed optical filaments.
AB  - We numerically investigate the propagation of a self-compressed optical filament
      through a gas-glass-gas interface. Few-cycle light pulses survive a sudden and
      short order-of-magnitude increase of nonlinearity and dispersion, even when all
      conservative estimates predict temporal spreading or spatial breakup.
      Spatiotemporal distortions are shown to self-heal upon further propagation when
      the pulse refocuses in the second gas. This self-healing mechanism has important
      implications for pulse compression techniques handled by filamentation and
      explains the robustness of such sources.

PMID- 19113412
TI  - Repeller or attractor? Selecting the dynamical model for the onset of turbulence
      in pipe flow.
AB  - The collapse of turbulence, observable in shear flows at low Reynolds numbers,
      raises the question if turbulence is generically of a transient nature or becomes
      sustained at some critical point. Recent data have led to conflicting views with
      the majority of studies supporting the model of turbulence turning into an
      attracting state. Here we present lifetime measurements of turbulence in pipe
      flow spanning 8 orders of magnitude in time, drastically extending all previous
      investigations. We show that no critical point exists in this regime and that in
      contrast to the prevailing view the turbulent state remains transient. To our
      knowledge this is the first observation of superexponential transients in
      turbulence, confirming a conjecture derived from low-dimensional systems.

PMID- 19113401
TI  - Search for gravitational-wave bursts from soft gamma repeaters.
AB  - We present a LIGO search for short-duration gravitational waves (GWs) associated
      with soft gamma ray repeater (SGR) bursts. This is the first search sensitive to
      neutron star f modes, usually considered the most efficient GW emitting modes. We
      find no evidence of GWs associated with any SGR burst in a sample consisting of
      the 27 Dec. 2004 giant flare from SGR 1806-20 and 190 lesser events from SGR 1806
      20 and SGR 1900+14. The unprecedented sensitivity of the detectors allows us to
      set the most stringent limits on transient GW amplitudes published to date. We
      find upper limit estimates on the model-dependent isotropic GW emission energies
      (at a nominal distance of 10 kpc) between 3x10;{45} and 9x10;{52} erg depending
      on waveform type, detector antenna factors and noise characteristics at the time
      of the burst. These upper limits are within the theoretically predicted range of
      some SGR models.

PMID- 19113413
TI  - Bifurcation from bubble to droplet behavior in inviscid pinch-off.
AB  - High-speed video is used to analyze the pinch-off of xenon in water. By varying
      the pressure in the xenon from 0.05 to 68 atm, the mass density ratio
      D=rho(int)/rho(ext) of the interior gaseous xenon rho(int} to the exterior liquid
      water rho(ext) can be varied by over 3 orders of magnitude. Both the shape of the
      pinch region and the power law that governs the collapse of the minimum neck
      radius are distinctly different for the low D (bubblelike) and high D
      (dropletlike) cases. We show that there is a rather abrupt transition between
      these types of behavior near D approximately 0.25.

PMID- 19113414
TI  - Pattern forming system in the presence of different symmetry-breaking mechanisms.
AB  - We report experiments on spatially forced inclined layer convection, where the
      combined effect of the intrinsic symmetry breaking due to a gravity-induced shear
      flow and spatially periodic 1D forcing is studied. We observed pattern selection
      processes resulting in stabilization of spatiotemporal chaos and the emergence of
      novel two-dimensional states. Phase diagrams depicting the different observed
      states for typical forcing scenarios are presented. Convection in the weakly
      nonlinear regime is compared with theory, and a good agreement is found.

PMID- 19113415
TI  - Dissipation in a sheared foam: from bubble adhesion to foam rheology.
AB  - The link between the rheology of 3D aqueous foam and the adhesion of neighboring
      bubbles is tested by confronting experiments at two different length scales. On
      the one hand, the dynamics of adhesion are probed by measuring how the shape of
      two bubbles in contact changes as their center-to-center distance is modulated.
      On the other hand, the linear viscoelastic behavior of 3D foam prepared with the
      same soapy solution is characterized by its complex shear modulus. To connect the
      two sets of data, we present a model of foam viscoelasticity taking into account
      bubble adhesion.

PMID- 19113416
TI  - Dynamic equilibrium mechanism for surface nanobubble stabilization.
AB  - Recent experiments have convincingly demonstrated the existence of surface
      nanobubbles on submerged hydrophobic surfaces. However, classical theory dictates
      that small gaseous bubbles quickly dissolve because their large Laplace pressure
      causes a diffusive outflux of gas. Here we suggest that the bubbles are
      stabilized by a continuous influx of gas near the contact line, due to the gas
      attraction towards hydrophobic walls [Dammer and Lohse, Phys. Rev. Lett. 96,
      206101 (2006); 10.1103/PhysRevLett.96.206101Zhang, Phys. Rev.
      Lett.10.1103/PhysRevLett.98.136101 98, 136101 (2007);
      10.1103/PhysRevLett.98.136101Mezger, J. Chem. Phys. 128, 244705
      (2008)10.1063/1.2931574]. This influx balances the outflux and allows for a
      metastable equilibrium, which, however, vanishes in thermodynamic equilibrium.
      Our theory predicts the equilibrium radius of the surface nanobubbles, as well as
      the threshold for surface nanobubble formation as a function of hydrophobicity
      and gas concentration.

PMID- 19113403
TI  - Measurement of the electron charge asymmetry in pp[over ]-->W+X-->enu+X events at
      sqrt[s]=1.96 TeV.
AB  - We present a measurement of the electron charge asymmetry in pp[over ]-->W+X-
      >enu+X events at a center of mass energy of 1.96 TeV using 0.75 fb(-1) of data
      collected with the D0 detector at the Fermilab Tevatron Collider. The asymmetry
      is measured as a function of the electron transverse momentum and pseudorapidity
      in the interval (-3.2, 3.2) and is compared with expectations from next-to
      leading order calculations in perturbative quantum chromodynamics. These
      measurements will allow more accurate determinations of the proton parton
      distribution functions.

PMID- 19113417
TI  - Electron force balance in steady collisionless-driven reconnection.
AB  - Steady collisionless-driven reconnection in an open system is investigated by
      means of full-particle simulations. A long thin electron current sheet extends
      towards the outflow direction when the system relaxes to a steady state. Although
      the pressure tensor term along the reconnection electric field contributes to the
      violation of the electron frozen-in condition, a new force balance in the inflow
      direction is realized between the Lorentz and electrostatic forces, which is
      quite different from that in Harris equilibrium. The strong electrostatic field
      is generated through the combined effect of the Hall term and a driving inflow.
      This new force balance is more evident in the three-dimensional case due to the
      growth of an instability along the reconnection electric field. It is also found
      that the normalized charge density is in proportion to the square of the electron
      Alfven velocity averaged over the electron dissipation region.

PMID- 19113418
TI  - Effect of quasihelical symmetry on trapped-electron mode transport in the HSX
      stellarator.
AB  - This Letter presents theory-based predictions of anomalous electron thermal
      transport in the Helically Symmetric eXperiment stellarator, using an
      axisymmetric trapped-electron mode drift wave model. The model relies on
      modifications to a tokamak geometry that approximate the quasihelical symmetry in
      the Helically Symmetric eXperiment (particle trapping and local curvature) and is
      supported by linear 3D gyrokinetic calculations. Transport simulations predict
      temperature profiles that agree with experimental profiles outside a normalized
      minor radius of rho>0.3 and energy confinement times that agree within 10% of
      measurements. The simulations can reproduce the large measured electron
      temperatures inside rho<0.3 if an approximation for turbulent transport
      suppression due to shear in the radial electric field is included.

PMID- 19113419
TI  - Cyclotron maser radiation from an inhomogeneous plasma.
AB  - Cyclotron maser radiation is important in both laboratory devices such as
      gyrotrons and in space physics applications to phenomena such as auroral
      kilometric radiation. To understand the behavior, especially in the latter case
      where there is generally a localized region of instability, requires an
      understanding of how such instabilities behave in an inhomogeneous plasma. Here
      we consider, for simplicity, a simple ring distribution of electrons in either a
      step function variation of magnetic field or a continuous gradient. In each case
      we show that there can exist localized regions of instability from which waves,
      growing in time, can be radiated outwards.

PMID- 19113420
TI  - Unitary Fermi supersolid: the Larkin-Ovchinnikov phase.
AB  - We present strong theoretical evidence that a Larkin-Ovchinnikov (LOFF/FFLO)
      pairing phase is favored over the homogeneous superfluid and normal phases in
      three-dimensional unitary Fermi systems. Using a density functional theory (DFT)
      based on the latest quantum Monte Carlo calculations and experimental results, we
      show that this phase is competitive over a large region of the phase diagram. The
      oscillations in the number densities and pairing field have a substantial
      amplitude, and a period some 3 to 10 times the average interparticle separation.
      Within the DFT, the transition to a normal polarized Fermi liquid at large
      polarizations is smooth, while the transition to a fully paired superfluid is
      abrupt.

PMID- 19113421
TI  - Reconnection of superfluid vortex bundles.
AB  - Using the vortex filament model and the Gross-Pitaevskii nonlinear Schroedinger
      equation, we show that bundles of quantized vortex lines in He II are
      structurally robust and can reconnect with each other maintaining their identity.
      We discuss vortex stretching in superfluid turbulence and show that, during the
      bundle reconnection process, kelvin waves of large amplitude are generated, in
      agreement with the finding that helicity is produced by nearly singular vortex
      interactions in classical Euler flows.

PMID- 19113422
TI  - Elasticity of floppy and stiff random networks.
AB  - We study the linear and nonlinear elastic behavior of amorphous systems using a
      two-dimensional random network of harmonic springs as a model system. A natural
      characterization of these systems arises in terms of the network coordination
      (average number of springs per node) relative to that of a marginally rigid
      network deltaz: a floppy network has deltaz<0, while a stiff network has
      deltaz>0. Under the influence of an externally applied load, we observe that the
      response of both floppy and stiff networks is controlled by the critical point
      corresponding to the onset of rigidity. We use numerical simulations to compute
      the exponents which characterize the shear modulus, the heterogeneity of the
      response, and the network stiffening as a function of deltaz and derive these
      theoretically, thus allowing us to predict aspects of the mechanical response of
      glasses and fibrous networks.

PMID- 19113423
TI  - Utilizing mechanical strain to mitigate the intrinsic loss mechanisms in
      oscillating metal nanowires.
AB  - We utilize classical molecular dynamics to study energy dissipation (the Q
      factors) of doubly clamped copper nanowire nanoresonators undergoing flexural
      oscillations. We find that the application of tensile strain effectively
      mitigates both the intrinsic surface and thermal losses, with improvements in Q
      by a factor of 3-10 across a range of operating temperatures. We also find that
      the nanowire Q factors are not dependent on the surface area to volume ratio, but
      instead their aspect ratio, and that the Q factors exhibit a 1/T(0.70) dependence
      on the temperature T that is independent of strain.

PMID- 19113424
TI  - Self-diffusion of particles in complex fluids: temporary cages and permanent
      barriers.
AB  - We study self-diffusion in complex fluids within dynamic density functional
      theory and explicitly account for the coupling to the fluctuating background.
      Applying the formalism to nematic and smectic liquid crystals, we find the
      temporary cages formed by neighboring particles to compete with permanent
      barriers in nonuniform systems, resulting in non-Gaussian diffusive motion that
      in different directions becomes correlated. Qualitative agreement with recent
      experiments demonstrates the importance of explicitly dealing with time-dependent
      self-consistent molecular fields.

PMID- 19113425
TI  - Path integral treatment of proton transport processes in BaZrO3.
AB  - Nuclear quantum effects on proton transfer and reorientation in BaZrO3 is
      investigated theoretically using the ab initio path-integral molecular-dynamics
      simulation technique. The result demonstrates that adding quantum fluctuations
      has a large effect on, in particular, the transfer barrier. The corresponding
      rates and diffusion coefficient are evaluated using the path-centroid transition
      state theory. In contrast with what is found assuming classical mechanics for the
      nuclear motion, the reorientation step becomes rate limiting below 600 K.

PMID- 19113426
TI  - Electronic nature of step-edge barriers against adatom descent on transition
      metal surfaces.
AB  - By studying a series of adatoms on representative transition-metal surfaces
      through first-principles calculations, we establish a clear correlation between
      the preferred mechanism and activation energy for adatom descent at a step and
      the relative degree of electronic shell filling of the adatom and the substrate.
      We also find an approximate linear relation between the adatom step-edge hopping
      barriers and the adatom-surface bonding strength with slope roughly proportional
      to the number of the adatom's nearest neighbors initially. These results may
      serve as simple guiding rules for predicting precise atomic surface morphologies
      in heteroepitaxial growth, as in formation of nanowires.

PMID- 19113427
TI  - Theory of directed nucleation of strained islands on patterned substrates.
AB  - We develop a theoretical model to elucidate the nucleation of strained islands on
      patterned substrates. We show that island nucleation is directed to the preferred
      sites by a much lower energy barrier and smaller critical size. Strain relaxation
      directs island nucleation to the bottom of a pit rather than the top of a ridge
      as commonly perceived, while large surface energy anisotropy favors nucleation at
      both places. The theory explains some puzzling experimental results and provides
      useful guidelines for future experiments.

PMID- 19113428
TI  - Cleaving-temperature dependence of layered-oxide surfaces.
AB  - The surfaces generated by cleaving nonpolar, two-dimensional oxides are often
      considered to be perfect or ideal. However, single particle spectroscopies on
      Sr2RuO4, an archetypal nonpolar two-dimensional oxide, show significant cleavage
      temperature dependence. We demonstrate that this is not a consequence of the
      intrinsic characteristics of the surface: lattice parameters and symmetries, step
      heights, atom positions, or density of states. Instead, we find a marked increase
      in the density of defects at the mesoscopic scale with increased cleave
      temperature. The potential generality of these defects to oxide surfaces may have
      broad consequences to interfacial control and the interpretation of surface
      sensitive measurements.

PMID- 19113429
TI  - Kinetically suppressed ostwald ripening of Ge/Si(100) hut clusters.
AB  - Low area density Ge/Si(100) hut cluster ensembles are stable during days-long
      growth temperature anneals. Real-time scanning tunneling microscopy shows that
      all islands grow slowly at a decreasing rate throughout the anneal. Island growth
      depletes the Ge supersaturation that, in turn, reduces the island growth rate. A
      mean-field facet nucleation and growth model quantitatively predicts the observed
      growth rate. It shows that Ostwald ripening is kinetically suppressed for Ge
      supersaturations high enough to support a critical nucleus size less than the
      smallest facet.

PMID- 19113430
TI  - Strongly reshaped organic-metal interfaces: tetracyanoethylene on Cu(100).
AB  - The interaction of the strong electron-acceptor tetracyanoethylene with the
      Cu(100) surface is studied with scanning tunneling microscopy experiments and
      first-principles density functional theory calculations. We compare two different
      adsorption models with the experimental results and show that the molecular self
      assembly is caused by a strong structural modification of the Cu(100) surface
      rather than the formation of a coordination network by diffusing Cu adatoms.
      Surface atoms become highly buckled, and the chemisorption of tetracyanoethylene
      is accompanied by a partial charge transfer.

PMID- 19113431
TI  - Kohn-Sham-like approach toward a classical density-functional theory of
      inhomogeneous polar molecular liquids: an application to liquid hydrogen
      chloride.
AB  - The Gordian knot of density-functional theories for classical molecular liquids
      remains finding an accurate free-energy functional in terms of the densities of
      the atomic sites of the molecules. Following Kohn and Sham, we show how to solve
      this problem by considering noninteracting molecules in a set of effective
      potentials. This shift in perspective leads to an accurate and computationally
      tractable description in terms of simple three-dimensional functions. We also
      treat both the linear- and saturation- dielectric responses of polar systems,
      presenting liquid hydrogen chloride as a case study.

PMID- 19113432
TI  - Fermi surface of superconducting LaFePO determined from quantum oscillations.
AB  - We report extensive measurements of quantum oscillations in the normal state of
      the Fe-based superconductor LaFePO, (T(c) approximately 6 K) using low
      temperature torque magnetometry and transport in high static magnetic fields (45
      T). We find that the Fermi surface is in broad agreement with the band-structure
      calculations with the quasiparticle mass enhanced by a factor approximately 2.
      The quasi-two-dimensional Fermi surface consists of nearly nested electron and
      hole pockets, suggesting proximity to a spin or charge density wave instability.

PMID- 19113433
TI  - Evidence for lattice effects at the charge-ordering transition in (TMTTF)2X.
AB  - High-resolution thermal expansion measurements have been performed for exploring
      the mysterious "structureless transition" in (TMTTF)2X (X=PF(6) and AsF6), where
      charge ordering at T(CO) coincides with the onset of ferroelectric order.
      Particularly distinct lattice effects are found at T(CO) in the uniaxial
      expansivity along the interstack c direction. We propose a scheme involving a
      charge modulation along the TMTTF stacks and its coupling to displacements of the
      counteranions X-. These anion shifts, which lift the inversion symmetry enabling
      ferroelectric order to develop, determine the 3D charge pattern without
      ambiguity. Evidence is found for another anomaly for both materials at T(int)
      approximately 0.6T(CO) indicative of a phase transition related to the charge
      ordering.

PMID- 19113434
TI  - Nonadiabatic spin transfer torque in high anisotropy magnetic nanowires with
      narrow domain walls.
AB  - Current induced domain wall (DW) depinning of a narrow DW in out-of-plane
      magnetized (Pt/Co)_{3}/Pt multilayer elements is studied by magnetotransport. We
      find that for conventional measurements Joule heating effects conceal the real
      spin torque efficiency and so we use a measurement scheme at a constant sample
      temperature to unambiguously extract the spin torque contribution. From the
      variation of the depinning magnetic field with the current pulse amplitude we
      directly deduce the large nonadiabaticity factor in this material and we find
      that its amplitude is consistent with a momentum transfer mechanism.

PMID- 19113435
TI  - Tunable plasmonic crystals for edge magnetoplasmons of a two-dimensional electron
      system.
AB  - Plasmonic crystal effects analogous to photonic crystal phenomena such as zone
      folding and gap opening were observed for edge magnetoplasmons in a two
      dimensional electron system with a periodically corrugated boundary at microwave
      frequencies. Magnetic field dependent photovoltage data provide unequivocal
      evidence for Bragg reflection. Band gaps up to fifth order were observed. These
      gaps were investigated as a function of the electron density, the magnetic field,
      and the periodicity to demonstrate the tunability of the dispersive properties of
      these plasmonic crystals.

PMID- 19113436
TI  - Kondo effect in single atom contacts: the importance of the atomic geometry.
AB  - Co single atom junctions on copper surfaces are studied by scanning tunneling
      microscopy and ab initio calculations. The Kondo temperature of single cobalt
      atoms on the Cu(111) surface has been measured at various tip-sample distances
      ranging from tunneling to the point contact regime. The experiments show a
      constant Kondo temperature for a whole range of tip-substrate distances
      consistently with the predicted energy position of the spin-polarized d levels of
      Co. This is in striking difference to experiments on Co/Cu(100) junctions, where
      a substantial increase of the Kondo temperature has been found. Our calculations
      reveal that the different behavior of the Co adatoms on the two Cu surfaces
      originates from the interplay between the structural relaxations and the
      electronic properties in the near-contact regime.

PMID- 19113437
TI  - Phonon-mediated tunneling into graphene.
AB  - Recent scanning tunneling spectroscopy experiments on graphene reported an
      unexpected gap of about +/-60 meV around the Fermi level [V. W. Brar, Appl. Phys.
      Lett. 91, 122102 (2007); 10.1063/1.2771084Y. Zhang, Nature Phys. 4, 627
      (2008)10.1038/nphys1022]. Here we give a theoretical investigation explaining the
      experimentally observed spectra and confirming the phonon-mediated tunneling as
      the reason for the gap: We study the real space properties of the wave functions
      involved in the tunneling process by means of ab initio theory and present a
      model for the electron-phonon interaction, which couples the graphene's Dirac
      electrons with quasifree-electron states at the Brillouin zone center. The self
      energy associated with this electron-phonon interaction is calculated, and its
      effects on tunneling into graphene are discussed. Good agreement of the tunneling
      density of states within our model and the experimental dI/dU spectra is found.

PMID- 19113438
TI  - Spin, orbital, and charge order at the interface between correlated oxides.
AB  - The collective behavior of correlated electrons in the VO2 interface layer of the
      LaVO(3)/SrTiO(3) heterostructure is studied within a quarter-filled t(2g)-orbital
      Hubbard model on a square lattice. We argue that the ground state is
      ferromagnetic, driven by the double-exchange mechanism, and is orbitally and
      charge ordered due to a confined geometry and electron correlations. The orbital
      and charge density waves open gaps on the entire Fermi surfaces of all orbitals.
      The theory explains the observed insulating behavior of the p-type interface
      between LaVO3 and SrTiO3.

PMID- 19113439
TI  - Spin rotations induced by an electron running in closed trajectories in gated
      semiconductor nanodevices.
AB  - A design for a quantum gate performing transformations of a single electron spin
      is presented. The spin rotations are performed by the electron going around the
      closed loops in a gated semiconductor device. We demonstrate the operation of
      NOT, phase-flip, and Hadamard quantum gates, i.e., the single-qubit gates which
      are most commonly used in the algorithms. The proposed devices employ the self
      focusing effect for the electron wave packet interacting with the electron gas on
      the electrodes and the Rashba spin-orbit coupling. Because of the self-focusing
      effect, the electron moves in a compact wave packet. The spin-orbit coupling
      translates the spatial motion of the electron into the rotations of the spin. The
      device does not require microwave radiation and operates using low constant
      voltages. It is therefore suitable for selective single-spin rotations in larger
      registers.

PMID- 19113440
TI  - Coulomb drag in quantum circuits.
AB  - We study the drag effect in a system of two electrically isolated quantum point
      contacts, coupled by Coulomb interactions. Drag current exhibits maxima as a
      function of quantum point contacts gate voltages when the latter are tuned to the
      transitions between quantized conductance plateaus. In the linear regime this
      behavior is due to enhanced electron-hole asymmetry near an opening of a new
      conductance channel. In the nonlinear regime the drag current is proportional to
      the shot noise of the driving circuit, suggesting that the Coulomb drag
      experiments may be a convenient way to measure the quantum shot noise.
      Remarkably, the transition to the nonlinear regime may occur at driving voltages
      substantially smaller than the temperature.

PMID- 19113441
TI  - Effects of electron-electron scattering in wide ballistic microcontacts.
AB  - We calculate the corrections to the Sharvin conductance of ballistic multimode
      microcontacts that result from electron-electron scattering in the leads. Using a
      semiclassical Boltzmann equation, we obtain that these corrections are positive
      and scale with temperature as T(2)ln(EF/T) for three-dimensional contacts and as
      T for two-dimensional ones. These results are relevant to recent experiments on
      two-dimensional electron gas contacts.

PMID- 19113442
TI  - Magnetization and spin excitations of non-Abelian quantum Hall states.
AB  - Significant insights into non-Abelian quantum Hall states are obtained from
      studying special multiparticle interaction Hamiltonians, whose unique ground
      states are the Moore-Read and Read-Rezayi states for the case of spinless
      electrons. We generalize this approach to include the electronic spin-1/2 degree
      of freedom. We demonstrate that in the absence of Zeeman splitting, the ground
      states of such Hamiltonians have large degeneracies and very rich spin
      structures. The spin structure of the ground states and low-energy excitations
      can be understood based on an emergent SU(3) symmetry for the case corresponding
      to the Moore-Read state. These states with different spin quantum numbers
      represent non-Abelian quantum Hall states with different magnetizations, whose
      quasihole properties are likely to be similar to those of their spin-polarized
      counterparts.

PMID- 19113443
TI  - Distributions of conductance and shot noise and associated phase transitions.
AB  - For a chaotic cavity with two identical leads each supporting N channels, we
      compute analytically, for large N, the full distribution of the conductance and
      the shot noise power and show that in both cases there is a central Gaussian
      region flanked on both sides by non-Gaussian tails. The distribution is weakly
      singular at the junction of Gaussian and non-Gaussian regimes, a direct
      consequence of two phase transitions in an associated Coulomb gas problem.

PMID- 19113444
TI  - Pairing symmetry and Josephson current in doped 2-leg t-J ladders.
AB  - We perform the numerical equivalent of a phase sensitive experiment on doped 2
      leg t-J ladders. We apply proximity effect fields with different complex phases
      at both ends of an open system and we study the transport of Cooper pairs.
      Measuring the response of the system and the induced Josephson current, density
      matrix renormalization group calculations show how, depending on the doping
      fraction, the rung-leg parity of the pair field changes from minus to plus as the
      density of holes is increased. The Josephson current exhibits a phase transition
      as a function of J/t.

PMID- 19113445
TI  - Crystalline electric field as a probe for long-range antiferromagnetic order and
      superconducting state of CeFeAsO(1-x)F(x).
AB  - We use inelastic neutron scattering to study the crystalline electric field (CEF)
      excitations of Ce3+ in CeFeAsO(1-x)F(x) (x=0, 0.16). For nonsuperconducting
      CeFeAsO, the Ce CEF levels have three magnetic doublets in the paramagnetic
      state, but these doublets split into six singlets when the Fe ions order
      antiferromagnetically. For superconducting CeFeAsO0.84F0.16 T(c)=41 K), where the
      static antiferromagnetic order is suppressed, the Ce CEF levels have three
      magnetic doublets at [formula: see text], 18.7, 58.4 meV at all temperatures.
      Careful measurements of the intrinsic linewidth Gamma and the peak position of
      the 18.7 meV mode reveal a clear anomaly at T(c), consistent with a strong
      enhancement of local magnetic susceptibility chi'' [formula: see text] below
      T(c). These results suggest that CEF excitations in the rare-earth oxypnictides
      can be used as a probe of spin dynamics in the nearby FeAs planes.

PMID- 19113446
TI  - Spin-electric coupling in molecular magnets.
AB  - We study the triangular antiferromagnet Cu3 in external electric fields, using
      symmetry group arguments and a Hubbard model approach. We identify a spin
      electric coupling caused by an interplay between spin exchange, spin-orbit
      interaction, and the chirality of the underlying spin texture of the molecular
      magnet. This coupling allows for the electric control of the spin (qubit) states,
      e.g., by using an STM tip or a microwave cavity. We propose an experimental test
      for identifying molecular magnets exhibiting spin-electric effects.

PMID- 19113447
TI  - Tailoring of the perpendicular magnetization component in ferromagnetic films on
      a vicinal substrate.
AB  - We have engineered the magnetic properties of 1-8 nm Co films epitaxially grown
      on an Au-buffered bifacial W(110)/W(540) single crystal. The surface of Au/W(110)
      was atomically flat, whereas the Au/W(540) followed the morphology of the vicinal
      W surface, showing a regular array of monoatomic steps. For Co grown on
      Au/W(540), the existence of the out-of-plane magnetization component extended
      strongly to a thickness d of about 8 nm, which was accompanied by an anomalous
      increase of the out-of-plane switching field with increasing d. In addition, the
      process of up-down magnetization switching could be realized with both a
      perpendicular and in-plane external magnetic field.

PMID- 19113448
TI  - Vibrational Kondo effect in pure organic charge-transfer assemblies.
AB  - A Kondo resonance has been observed using a scanning tunneling microscope on a
      single molecular layer of a purely organic charge-transfer salt grown on a metal
      surface. Analysis of the Kondo anomaly reveals that the electron acceptor of the
      film possesses a spin-1/2 ground state due to the localization of an unpaired
      electron in the conjugated lowest unoccupied molecular orbital. Because of the pi
      character of this molecular state the unpaired electron is strongly coupled to
      molecular vibrations, leading to the split of the Kondo resonance in vibrational
      sidebands.

PMID- 19113449
TI  - Evidence for barrierless auger recombination in PbSe nanocrystals: a pressure
      dependent study of transient optical absorption.
AB  - We report rates of Auger recombination (AR) in zero-dimensional (0D) PbSe
      nanocrystals as a function of energy gap (Eg) by using applied hydrostatic
      pressure to controllably shift E(g) according to the bulk deformation potential.
      Our studies reveal that the rate of AR in nanocrystals is insensitive to energy
      gap, which is in contrast with bulk semiconductors where this rate shows
      exponential dependence on E(g). These measurements represent the first direct
      experimental evidence that AR in 0D nanomaterials is barrierless, in distinction
      from bulk semiconductors.

PMID- 19113450
TI  - Ultrafast exciton dephasing in semiconducting single-walled carbon nanotubes.
AB  - Femtosecond two-pulse degenerate four-wave mixing spectroscopy was applied to
      study the exciton dephasing in a broad range of excitation intensities and
      lattice temperatures. We find that both exciton-exciton and exciton-phonon
      scattering have profound effects on the dephasing process. The dominant phonon
      mode involved in the dephasing is identified as the out-of-plane, transverse
      optical mode with a frequency of 847 cm(-1). The extracted homogeneous linewidths
      at all measured temperatures are in excellent agreement with the results of a
      single-tube photoluminescence experiment.

PMID- 19113451
TI  - Quantum control of a trapped electron spin in a quantum dot using photon
      polarization.
AB  - We present an original scheme to rotate at will one electron spin trapped in a
      quantum dot by just acting on pump-laser polarization: The quantum control is
      based on the virtual excitation of electron light-hole pairs with pi symmetry, as
      possibly done by using a single laser beam with a propagation axis slightly
      tilted with respect to a weak magnetic field. This allows us to fully control the
      effective axis of the electron spin rotation through the pump polarization. Our
      analysis shows that quantum dots with inverted valence states are ideal
      candidates for ultrafast, high-fidelity, all optical control.

PMID- 19113452
TI  - Relevance of Abelian symmetry and stochasticity in directed sandpiles.
AB  - We provide a comprehensive view of the role of Abelian symmetry and stochasticity
      in the universality class of directed sandpile models, in the context of the
      underlying spatial correlations of metastable patterns and scars. It is argued
      that the relevance of Abelian symmetry may depend on whether the dynamic rule is
      stochastic or deterministic, by means of the interaction of metastable patterns
      and avalanche flow. Based on the new scaling relations, we conjecture critical
      exponents for an avalanche, which is confirmed reasonably well in large-scale
      numerical simulations.

PMID- 19113453
TI  - Self-organized periodicity of protein clusters in growing bacteria.
AB  - Chemotaxis receptors in E. coli form clusters at the cell poles and also
      laterally along the cell body, and this clustering plays an important role in
      signal transduction. Recently, experiments using fluorescence imaging have shown
      that, during cell growth, lateral clusters form at positions approximately
      periodically spaced along the cell body. In this Letter, we demonstrate within a
      lattice model that such spatial organization could arise spontaneously from a
      stochastic nucleation mechanism. The same mechanism may explain the recent
      observation of periodic aggregates of misfolded proteins in E. coli.

PMID- 19113454
TI  - Non-Markovian model for transport and reactions of particles in spiny dendrites.
AB  - Motivated by the experiments [Santamaria, Neuron 52, 635
      (2006)10.1016/j.neuron.2006.10.025] that indicated the possibility of
      subdiffusive transport of molecules along dendrites of cerebellar Purkinje cells,
      we develop a mesoscopic model for transport and chemical reactions of particles
      in spiny dendrites. The communication between spines and a parent dendrite is
      described by a non-Markovian random process and, as a result, the overall
      movement of particles can be subdiffusive. A system of integrodifferential
      equations is derived for the particles densities in dendrites and spines. This
      system involves the spine-dendrite interaction term which describes the memory
      effects and nonlocality in space. We consider the impact of power-law waiting
      time distributions on the transport of biochemical signals and mechanism of the
      accumulation of plasticity-inducing signals inside spines.

PMID- 19113455
TI  - High resolution shear profile measurements in entangled polymers.
AB  - We use confocal microscopy and particle image velocimetry to visualize motion of
      250-300 nm. fluorescent tracer particles in entangled polymers subject to a
      rectilinear shear flow. Our results show linear velocity profiles in polymer
      solutions spanning a wide range of molecular weights and number of entanglements
      (8< or =Z< or =56), but reveal large differences between the imposed and measured
      shear rates. These findings disagree with recent reports that shear banding is a
      characteristic flow response of entangled polymers, and instead point to
      interfacial slip as an important source of strain loss.

PMID- 19113456
TI  - Colloidal ordering on a 2D quasicrystalline substrate.
AB  - By using Monte Carlo simulations, we study the complex phase behavior of charged
      stabilized colloidal particles in a two-dimensional substrate potential with
      quasicrystalline decagonal symmetry. In the regime where the strengths of the
      substrate and colloidal pair potential are comparable, we identify a novel and
      unexpected quasicrystalline phase with pure 20-fold bond order and a disordered
      structure without any apparent rotational symmetry. Furthermore, we demonstrate
      how phasonic displacements in the substrate potential induce phasonic flips in
      the colloidal monolayer.

PMID- 19113457
TI  - Self-organized gels in DNA/F-actin mixtures without crosslinkers: networks of
      induced nematic domains with tunable density.
AB  - We examine mixtures of DNA and filamentous actin (F-actin) as a model system of
      like-charged rigid rods and flexible chains. Confocal microscopy reveals the
      formation of elongated nematic F-actin domains reticulated via defect-free
      vertices into a network embedded in a mesh of random DNA. Synchrotron x-ray
      scattering results indicate that the DNA mesh squeezes the F-actin domains into a
      nematic state with an interactin spacing that decreases with increasing DNA
      concentration as d(actin) proportional, variantrho(DNA)(-1/2). Interestingly, the
      system changes from a counterion-controlled regime to a depletion-controlled
      regime with added salt, with drastic consequences for the osmotic pressure
      induced phase behavior.

PMID- 19113458
TI  - Controlled swimming in confined fluids of magnetically actuated colloidal rotors.
AB  - We show that DNA-linked anisotropic doublets composed of paramagnetic colloidal
      particles can be endowed with controlled propulsion when floating above a flat
      plate and subjected to a magnetic field precessing around an axis parallel to the
      plate. The propulsion mechanism for this artificial swimmer does not involve
      deformations, and it makes use of the minimal two degrees of freedom needed to
      propel it at low Reynolds numbers. We combine experimental observations with a
      theoretical analysis that fully characterizes the propulsion velocity in terms of
      the strength and frequency of the actuating magnetic field.

PMID- 19113459
TI  - Empirical tests of Zipf's law mechanism in open source Linux distribution.
AB  - Zipf's power law is a ubiquitous empirical regularity found in many systems,
      thought to result from proportional growth. Here, we establish empirically the
      usually assumed ingredients of stochastic growth models that have been previously
      conjectured to be at the origin of Zipf's law. We use exceptionally detailed data
      on the evolution of open source software projects in Linux distributions, which
      offer a remarkable example of a growing complex self-organizing adaptive system,
      exhibiting Zipf's law over four full decades.

PMID- 19113460
TI  - Maximum power efficiency and criticality in random Boolean networks.
AB  - Random Boolean networks are models of disordered causal systems that can occur in
      cells and the biosphere. These are open thermodynamic systems exhibiting a flow
      of energy that is dissipated at a finite rate. Life does work to acquire more
      energy, then uses the available energy it has gained to perform more work. It is
      plausible that natural selection has optimized many biological systems for power
      efficiency: useful power generated per unit fuel. In this Letter, we begin to
      investigate these questions for random Boolean networks using Landauer's erasure
      principle, which defines a minimum entropy cost for bit erasure. We show that
      critical Boolean networks maximize available power efficiency, which requires
      that the system have a finite displacement from equilibrium. Our initial results
      may extend to more realistic models for cells and ecosystems.

PMID- 19113461
TI  - Comment on "Using compound kinoform hard-X-ray lenses to exceed the critical
      angle limit".

PMID- 19113463
TI  - Spin echo in spinor dipolar Bose-Einstein condensates.
AB  - We theoretically propose and numerically realize spin echo in a spinor Bose
      Einstein condensate (BEC). We investigate the influence on the spin echo of phase
      separation of the condensate. The equation of motion of the spin density exhibits
      two relaxation times. We use two methods to separate the relaxation times and
      hence demonstrate a technique to reveal magnetic dipole-dipole interactions in
      spinor BECs.

PMID- 19113464
TI  - Microscopic expression for heat in the adiabatic basis.
AB  - We derive a microscopic expression for the instantaneous diagonal elements of the
      density matrix rho(nn)(t) in the adiabatic basis for an arbitrary time-dependent
      process in a closed Hamiltonian system. If the initial density matrix is
      stationary (diagonal) then this expression contains only squares of absolute
      values of matrix elements of the evolution operator, which can be interpreted as
      transition probabilities. We then derive the microscopic expression for the heat
      defined as the energy generated due to transitions between instantaneous energy
      levels. If the initial density matrix is passive [diagonal with rho(nn)(0)
      monotonically decreasing with energy] then the heat is non-negative in agreement
      with basic expectations of thermodynamics. Our findings also can be used for
      systematic expansion of various observables around the adiabatic limit.

PMID- 19113465
TI  - Entanglement of formation for an arbitrary two-mode Gaussian state.
AB  - We write the optimal pure-state decomposition of any two-mode Gaussian state and
      show that its entanglement of formation coincides with the Gaussian one. This
      enables us to develop an insightful approach of evaluating the exact entanglement
      of formation. Its additivity is finally proven.

PMID- 19113466
TI  - Approximate quantum cloaking and almost-trapped states.
AB  - We describe potentials which act as approximate cloaks for matter waves. These
      potentials are derived from ideal cloaks for the conductivity and Helmholtz
      equations. At most energies E, if a potential is surrounded by an approximate
      cloak, then it becomes almost undetectable and unaltered by matter waves
      originating externally to the cloak. For certain E, however, the approximate
      cloaks are resonant, supporting wave functions almost trapped inside the cloaked
      region and negligible outside. Applications include dc or magnetically tunable
      ion traps and beam switches.

PMID- 19113467
TI  - Quantum adiabatic algorithm for factorization and its experimental
      implementation.
AB  - We propose an adiabatic quantum algorithm capable of factorizing numbers, using
      fewer qubits than Shor's algorithm. We implement the algorithm in a NMR quantum
      information processor and experimentally factorize the number 21. In the range
      that our classical computer could simulate, the quantum adiabatic algorithm works
      well, providing evidence that the running time of this algorithm scales
      polynomially with the problem size.

PMID- 19113468
TI  - Quantum simulator for the Ising model with electrons floating on a helium film.
AB  - We propose a physical setup that can be used to simulate the quantum dynamics of
      the Ising model in a transverse field. Building on currently available
      technology, our scheme consists of electrons which float on a superfluid helium
      film covering a suitable substrate and interact via Coulomb forces. At low
      temperatures, the system will stay near its ground state where its Hamiltonian is
      equivalent to the Ising model and thus shows phenomena such as quantum
      criticality.

PMID- 19113469
TI  - Realization of a feedback controlled flashing ratchet.
AB  - A flashing ratchet transports diffusive particles using a time-dependent,
      asymmetric potential. The particle speed is predicted to increase when a feedback
      algorithm based on the particle position is used. We have experimentally realized
      such a feedback ratchet using an optical line trap, and observed that use of
      feedback increases velocity by up to an order of magnitude. We compare two
      different feedback algorithms for small particle numbers, and find good agreement
      with simulations. We also find that existing algorithms can be improved to be
      more tolerant to feedback delay times.

PMID- 19113470
TI  - Magic frequencies for cesium primary-frequency standard.
AB  - We consider microwave hyperfine transitions in the ground state of cesium and
      rubidium atoms which are presently used as the primary and the secondary
      frequency standards. The atoms are confined in an optical lattice generated by a
      circularly polarized laser field. We demonstrate that applying an external
      magnetic field with appropriately chosen direction may cancel dynamic Stark
      frequency shift making the frequency of the clock transition insensitive to the
      strengths of both the laser and the magnetic fields. This can be attained for
      practically any laser frequency which is sufficiently distant from a resonance.

PMID- 19113472
TI  - Universality of quantum gravity corrections.
AB  - We show that the existence of a minimum measurable length and the related
      generalized uncertainty principle (GUP), predicted by theories of quantum
      gravity, influence all quantum Hamiltonians. Thus, they predict quantum gravity
      corrections to various quantum phenomena. We compute such corrections to the Lamb
      shift, the Landau levels, and the tunneling current in a scanning tunneling
      microscope. We show that these corrections can be interpreted in two ways: (a)
      either that they are exceedingly small, beyond the reach of current experiments,
      or (b) that they predict upper bounds on the quantum gravity parameter in the
      GUP, compatible with experiments at the electroweak scale. Thus, more accurate
      measurements in the future should either be able to test these predictions, or
      further tighten the above bounds and predict an intermediate length scale between
      the electroweak and the Planck scale.

PMID- 19113471
TI  - Discovery of localized regions of excess 10-TeV cosmic rays.
AB  - The 7 year data set of the Milagro TeV observatory contains 2.2 x 10(11) events
      of which most are due to hadronic cosmic rays. These data are searched for
      evidence of intermediate scale structure. Excess emission on angular scales of
      approximately 10 degrees has been found in two localized regions of unknown
      origin with greater than 12sigma significance. Both regions are inconsistent with
      pure gamma-ray emission with high confidence. One of the regions has a different
      energy spectrum than the isotropic cosmic-ray flux at a level of 4.6sigma, and it
      is consistent with hard spectrum protons with an exponential cutoff, with the
      most significant excess at approximately 10 TeV. Potential causes of these
      excesses are explored, but no compelling explanations are found.

PMID- 19113473
TI  - Boom and bust inflation: a graceful exit via compact extra dimensions.
AB  - A model of inflation is proposed in which compact extra dimensions allow a
      graceful exit without recourse to flat potentials or super-Planckian field
      values. Though bubbles of true vacuum are too sparse to uniformly reheat the
      Universe by colliding with each other, a compact dimension enables a single
      bubble to uniformly reheat by colliding with itself. This mechanism, which
      generates an approximately scale invariant perturbation spectrum, requires that
      inflation be driven by a bulk field, that vacuum decay be slow, and that the
      extra dimension be at least a hundred times larger than the false vacuum Hubble
      length.

PMID- 19113476
TI  - Dijet searches for supersymmetry at the large hadron collider.
AB  - We present several strategies for searching for supersymmetry in dijet channels,
      using the two leading jets' momenta alone rather than the full missing transverse
      energy. Preliminary investigations suggest that signal-to-background ratios of at
      least 4-5 should be achievable at the LHC, with discovery possible for squarks as
      heavy as approximately 1.7 TeV.

PMID- 19113479
TI  - Leading SU(3)-breaking corrections to the baryon magnetic moments in chiral
      perturbation theory.
AB  - We calculate the baryon magnetic moments using covariant chiral perturbation
      theory (chiPT) within the extended-on-mass-shell renormalization scheme. By
      fitting the two available low-energy constants, we improve the Coleman-Glashow
      description of the data when we include the leading SU(3)-breaking effects coming
      from the lowest-order loops. This success is in dramatic contrast with previous
      attempts at the same order using heavy-baryon chiPT and covariant infrared chiPT.
      We also analyze the source of this improvement with particular attention to the
      comparison between the covariant results.

PMID- 19113480
TI  - Improved laboratory values of the H2 Lyman and Werner lines for constraining time
      variation of the proton-to-electron mass ratio.
AB  - Two distinct high-accuracy laboratory spectroscopic investigations of the H2
      molecule are reported. Anchor lines in the EF1Sigmag+-X1Sigmag+ system are
      calibrated by two-photon deep-UV Doppler-free spectroscopy, while independent
      Fourier-transform spectroscopic measurements are performed that yield accurate
      spacings in the B1Sigmau+-EF1Sigmag+ and I1Pig-C1Piu systems. From combination
      differences accurate transition wavelengths for the B-X Lyman and the C-X Werner
      lines can be determined with accuracies better than approximately 5 x 10(-9),
      representing a major improvement over existing values. This metrology provides a
      practically exact database to extract a possible variation of the proton-to
      electron mass ratio based on H2 lines in high-redshift objects. Moreover, it
      forms a rationale for equipping a future class of telescopes, carrying 30-40 m
      dishes, with novel spectrometers of higher resolving powers.

PMID- 19113481
TI  - Mechanism for electron transfer in fast ion-atomic collisions.
AB  - We discuss a mechanism for electron capture in fast ion-atom collisions which has
      not been considered so far. Similarly as in the radiative capture, where the
      electron transfer occurs due to photon emission, within the mechanism under
      consideration the electron capture takes place due to the emission of an
      additional electron. This first-order capture mechanism leads to the so-called
      transfer ionization and has a number of interesting features; in particular, in
      the target frame it results in electron emission mainly into the backward
      semisphere.

PMID- 19113477
TI  - Search for active neutrino disappearance using neutral-current interactions in
      the MINOS long-baseline experiment.
AB  - We report the first detailed comparisons of the rates and spectra of neutral
      current neutrino interactions at two widely separated locations. A depletion in
      the rate at the far site would indicate mixing between nu(mu) and a sterile
      particle. No anomalous depletion in the reconstructed energy spectrum is
      observed. Assuming oscillations occur at a single mass-squared splitting, a fit
      to the neutral- and charged-current energy spectra limits the fraction of nu(mu)
      oscillating to a sterile neutrino to be below 0.68 at 90% confidence level. A
      less stringent limit due to a possible contribution to the measured neutral
      current event rate at the far site from nu(e) appearance at the current
      experimental limit is also presented.

PMID- 19113482
TI  - Evidence of sequentially formed charge patches guiding ions through
      nanocapillaries.
AB  - We investigated the time evolution of the dynamically shifting distribution of 7
      keV Ne7+ ions guided through nanocapillaries in SiO2. We present evidence for a
      small number of charge patches, formed sequentially in the charging-up process,
      guiding the ions. We show that the charge patches are distributed along the whole
      length of the capillaries and that they are maintained in the equilibrium state
      of transmission. The interpretations are supported by model calculations.

PMID- 19113483
TI  - Fast excitation and photon emission of a single-atom-cavity system.
AB  - We report on the fast excitation of a single atom coupled to an optical cavity
      using laser pulses that are much shorter than all other relevant processes. The
      cavity frequency constitutes a control parameter that allows the creation of
      single photons in a superposition of two tunable frequencies. Each photon emitted
      from the cavity thus exhibits a pronounced amplitude modulation determined by the
      oscillatory energy exchange between the atom and the cavity. Our technique
      constitutes a versatile tool for future quantum networking experiments.

PMID- 19113484
TI  - Interaction of spiral waves in the complex Ginzburg-Landau equation.
AB  - Solutions of the general cubic complex Ginzburg-Landau equation comprising
      multiple spiral waves are considered, and laws of motion for the centers are
      derived. The direction of the motion changes from along the line of centers to
      perpendicular to the line of centers as the separation increases, with the
      strength of the interaction algebraic at small separations and exponentially
      small at large separations. The corresponding asymptotic wave number and
      frequency are also determined, which evolve slowly as the spirals move.

PMID- 19113485
TI  - Dynamic characterization of permeabilities and flows in microchannels.
AB  - We make an analytical study of the nonsteady flow of Newtonian fluids in
      microchannels. We consider the slip boundary condition at the solid walls with
      Navier hypothesis and calculate the dynamic permeability, which gives the
      system's response to dynamic pressure gradients. We find a scaling relation in
      the absence of slip that is broken in its presence. We discuss how this might be
      useful to experimentally determine--by means of microparticle image velocimetry
      technology--whether slip exists or not in a system, the value of the slip length,
      and the validity of Navier hypothesis in dynamic situations.

PMID- 19113475
TI  - Search for neutral Higgs bosons in multi-b-jet events in pp[over] collisions at
      sqrt[s]=1.96 TeV.
AB  - Data recorded by the D0 experiment at the Fermilab Tevatron Collider are analyzed
      to search for neutral Higgs bosons produced in association with b quarks. This
      production mode can be enhanced in the minimal supersymmetric standard model
      (MSSM). The search is performed in the three b quark channel using multijet
      triggered events corresponding to an integrated luminosity of 1 fb(-1). No
      statistically significant excess of events with respect to the predicted
      background is observed and limits are set in the MSSM parameter space.

PMID- 19113486
TI  - Model of Hall reconnection.
AB  - The rate of quasistationary, two-dimensional magnetic reconnection is calculated
      in the framework of incompressible Hall magnetohydrodynamics, which includes the
      Hall and electron pressure terms in Ohm's law. The Hall-magnetohydrodynamics
      equations are solved in a local region across the reconnection electron layer,
      including only the upstream region and the layer center. In the case when the ion
      inertial length di is larger than the Sweet-Parker reconnection layer thickness,
      the dimensionless reconnection rate is found to be independent of the electrical
      resistivity and equal to di/L, where L is the scale length of the external
      magnetic field in the upstream region outside the electron layer and the ion
      layer thickness is found to be di.

PMID- 19113487
TI  - Collisionless laser-energy conversion by anharmonic resonance.
AB  - After two decades of experiments with intense fs laser pulses the physical
      mechanism of collisionless absorption in overdense matter is still not
      understood. We show that anharmonic resonance in the self-generated plasma
      potential at a steep ion density profile may represent the leading physical
      absorption mechanism. Resonance provides for the phase shift of the free electron
      current which is compulsory for laser beam energy transfer to any medium and is
      capable of explaining the prompt generation of fast electrons with maximum
      energies exceeding many times their quiver energy, and the polarization
      dependence.

PMID- 19113478
TI  - Forward neutral-pion transverse single-spin asymmetries in p + p collisions at
      sqrt[s] = 200 GeV.
AB  - We report precision measurements of the Feynman x (xF) dependence, and first
      measurements of the transverse momentum (pT) dependence, of transverse single
      spin asymmetries for the production of pi0 mesons from polarized proton
      collisions at sqrt[s] = 200 GeV. The xF dependence of the results is in fair
      agreement with perturbative QCD model calculations that identify orbital motion
      of quarks and gluons within the proton as the origin of the spin effects. Results
      for the pT dependence at fixed xF are not consistent with these same perturbative
      QCD-based calculations.

PMID- 19113488
TI  - Kondo polarons in a one-dimensional Fermi gas.
AB  - We consider the motion of a spin-1/2 impurity in a one-dimensional gas of spin
      1/2 fermions. For antiferromagnetic interaction between the impurity and the
      fermions, the low temperature behavior of the system is governed by the two
      channel Kondo effect, leading to the impurity becoming completely opaque to the
      spin excitations of the gas. As well as the known spectral signatures of the two
      channel Kondo effect, we find that the low temperature mobility of the resulting
      "Kondo polaron" takes the universal form mu-->3variant Planck's over
      vF2/2pikB2T2, in sharp contrast to the spinless case where mu proportional
      variant T(-4).

PMID- 19113474
TI  - Search for anomalous Wtb couplings in single top quark production.
AB  - In 0.9 fb(-1) of pp[over] collisions, the D0 Collaboration presented evidence for
      single top quark production in events with an isolated lepton, missing transverse
      momentum, and two to four jets. We examine these data to study the Lorentz
      structure of the Wtb coupling. The standard model predicts a left-handed vector
      coupling at the Wtb vertex. The most general lowest dimension, CP-conserving
      Lagrangian admits right-handed vector and left- or right-handed tensor couplings
      as well. We find that the data prefer the left-handed vector coupling and set
      upper limits on the anomalous couplings. These are the first direct constraints
      on a general Wtb interaction and the first direct limits on left- and right
      handed tensor couplings.

PMID- 19113489
TI  - Origins of apparent fragile-to-strong transitions of protein hydration waters.
AB  - 2H NMR is used to study the mechanisms for the reorientation of protein hydration
      water. In the past, crossovers in temperature-dependent correlation times were
      reported at Tx1 approximately 225 K (X1) and Tx2 approximately 200 K (X2). We
      show that neither X1 nor X2 are related to a fragile-to-strong transition. Our
      results rule out an existence of X1. Also, they indicate that water performs
      thermally activated and distorted tetrahedral jumps at T < Tx2, implying that X2
      originates in an onset of this motion, which may be related to a universal defect
      diffusion in materials with defined hydrogen-bond networks.

PMID- 19113490
TI  - Water slippage versus contact angle: a quasiuniversal relationship.
AB  - Using molecular dynamics simulations of an atomistic water model, we study the
      interfacial hydrodynamic slippage of water at various hydrophobic surfaces, both
      organic (silane monolayers) and inorganic (diamondlike and Lennard-Jones models).
      The measured slip lengths range from nanometers to tens of nanometers. Slip
      lengths on different surfaces are found to collapse nearly onto a single curve as
      a function of the static contact angle characterizing the surface wettability,
      thereby suggesting a quasiuniversal relationship. This dependence is rationalized
      on the basis of a simple scaling description of the fluid-solid friction at the
      microscopic level. The link between slippage and water depletion at hydrophobic
      surfaces is clarified. These results shed light on the controversy over
      experimental measurements of the slip length at smooth hydrophobic surfaces.

PMID- 19113491
TI  - Anomalous mass transport in the Pb wetting layer on the Si(111) surface.
AB  - The temporal evolution of nonequilibrium coverage profiles in the Pb wetting
      layer on the Si(111) surface is studied using low energy electron microscopy. The
      initial coverage step profile propagates rapidly at a constant velocity with an
      unperturbed shape. A model is proposed that attributes this nonclassical
      equilibration behavior to the diffusion of thermally generated adatoms on top of
      the wetting layer. This model can account for the observed convectionlike mass
      transport, as well as its dramatic dependence on Pb coverage. Such anomalous mass
      transport is believed to facilitate the remarkably efficient self-organization of
      uniform Pb quantum island height on the Si(111) surface that was observed
      previously.

PMID- 19113492
TI  - Charge and orbital correlations at and above the Verwey phase transition in
      magnetite.
AB  - The subtle interplay among electronic degrees of freedom (charge and orbital
      orderings), spin and lattice distortion that conspire at the Verwey transition in
      magnetite (Fe3O4) is still a matter of controversy. Here, we provide compelling
      evidence that these electronic orderings are manifested as a continuous phase
      transition at the temperature where a spin reorientation takes place at around
      130 K, i.e., well above TV approximately 121 K. The Verwey transition seems to
      leave the orbital ordering unaffected whereas the charge ordering development
      appears to be quenched at this temperature and the temperature dependence below
      TV is controlled by the lattice distortions. Finally, we show that the orbital
      ordering does not reach true long range (disorder), and the correlation length
      along the c-direction is limited to 100 angstroms.

PMID- 19113493
TI  - Dimensionality-controlled insulator-metal transition and correlated metallic
      state in 5d transition metal oxides Sr n+1Ir nO3n+1 (n=1, 2, and infinity).
AB  - We investigated the electronic structures of the 5d Ruddlesden-Popper series Sr
      n+1Ir nO3n+1 (n=1, 2, and infinity) using optical spectroscopy and first
      principles calculations. As 5d orbitals are spatially more extended than 3d or 4d
      orbitals, it has been widely accepted that correlation effects are minimal in 5d
      compounds. However, we observed a Mott insulator-metal transition with a change
      of bandwidth as we increased n. In addition, the artificially synthesized
      perovskite SrIrO3 showed a very large mass enhancement of about 6, indicating
      that it was in a correlated metallic state.

PMID- 19113494
TI  - Ab initio electronic and optical properties of the N - v- center in diamond.
AB  - Despite tremendous activity in employing the N- V- center in a host of quantum
      technology applications, the electronic and optical properties of the system are
      still not theoretically well understood. We have conducted density functional
      theory calculations of the N- V- system which show convergence at the 3 x 3 x 3
      supercell level and for the first time produce a quantitatively accurate picture
      of the optical transition energy, excited-state lifetime, and optical
      polarization anisotropy taking into account all possible transitions within all
      contributing energy bands. These calculations were augmented by a group
      theoretical analysis, in sum providing a new ab initio understanding of this
      important solid-state quantum system.

PMID- 19113495
TI  - Using high energy angle resolved photoelectron spectroscopy to reveal the charge
      density in solids.
AB  - The charge density in solids is a fundamental parameter. Here we demonstrate that
      the charge density can be determined by the use of angle resolved photoelectron
      spectroscopy. The method, which involves a Fourier-like transform from momentum
      space to real space, is demonstrated by utilizing soft x-ray angle resolved
      photoelectron spectroscopy to sample the complete three-dimensional Brillouin
      zone of copper. It is also shown that this can be done in an energy resolved way
      as to extract the charge density contribution from states of a particular energy.

PMID- 19113496
TI  - Ab initio GW many-body effects in graphene.
AB  - We present an ab initio numerical many-body GW calculation of the band plot in
      freestanding graphene. We consider the full ionic and electronic structure
      introducing e-e interaction and correlation effects via a self-energy containing
      non-Hermitian and dynamical terms. With respect to the density-functional theory
      local-density approximation, the Fermi velocity is renormalized with an increase
      of 17%, in better agreement with the experiment. Close to the Dirac point the
      linear dispersion is modified by the presence of a kink, as observed by angle
      resolved photoemission spectroscopy. We demonstrate that the kink is due to low
      energy pi-->pi* single-particle excitations and to the pi plasmon. The GW self
      energy does not open the band gap.

PMID- 19113497
TI  - Primary role of the barely occupied states in the charge density wave formation
      of NbSe2.
AB  - NbSe2 is a prototypical charge-density-wave (CDW) material, whose mechanism
      remains mysterious so far. With angle resolved photoemission spectroscopy, we
      recovered the long-lost nesting condition over a large broken-honeycomb region in
      the Brillouin zone, which consists of six saddle band point regions with high
      density of states (DOS), and large regions away from Fermi surfaces with
      negligible DOS at the Fermi energy. We show that the major contributions to the
      CDW formation come from these barely occupied states rather than the saddle band
      points. Our findings not only resolve a long-standing puzzle, but also overthrow
      the conventional wisdom that CDW is dominated by regions with high DOS.

PMID- 19113498
TI  - Second critical point in first order metal-insulator transitions.
AB  - For first order metal-insulator transitions we show that, together with the dc
      conductance zero, there is a second critical point where the dielectric constant
      becomes zero and further turns negative. At this point the metallic reflectivity
      sharply increases. The two points can be separated by a phase separation state in
      a 3D disordered system but may tend to merge in 2D. For illustration we evaluate
      the dielectric function in a simple effective medium approximation and show that
      at the second point it turns negative. We reproduce the experimental data on a
      typical Mott insulator such as MnO, demonstrating the presence of the two points
      clearly. We discuss other experiments for studies of the phase separation state
      and a similar phase separation in superconductors with insulating inclusions.

PMID- 19113499
TI  - Direct evidence for the effect of quantum confinement of surface-state electrons
      on atomic diffusion.
AB  - We report on the direct observations of the effect of quantum confinement of
      surface-state electrons on atomic diffusion. Confined electronic states induced
      by open nanoscale resonators [consisting of two parallel monatomic Cu chains on
      Cu(111)] are studied by means of scanning tunneling microscope measurements and
      first-principles calculations. Strongly anisotropic diffusion of adatoms around
      and inside resonators is revealed at low temperatures. The formation of diffusion
      channels and empty zones is demonstrated. We show that it is possible to engineer
      atomic diffusion by varying the distance between the resonator walls.

PMID- 19113500
TI  - Mesoscopic fluctuations in the spin-electric susceptibility due to Rashba spin
      orbit interaction.
AB  - We investigate mesoscopic fluctuations in the spin polarization generated by a
      static electric field and by Rashba spin-orbit interaction in a disordered 2D
      electron gas. In a diagrammatic approach we find that the out-of-plane
      polarization--while being zero for self-averaging systems--exhibits large sample
      to-sample fluctuations which are shown to be well within experimental reach. We
      evaluate the disorder-averaged variance of the susceptibility and find its
      dependence on magnetic field, spin-orbit interaction, dephasing, and chemical
      potential difference.

PMID- 19113501
TI  - Insitu reduction of charge noise in GaAs/AlxGa1-xAs Schottky-gated devices.
AB  - We show that an insulated electrostatic gate can be used to strongly suppress
      ubiquitous background charge noise in Schottky-gated GaAs/AlGaAs devices. Via a
      2D self-consistent simulation of the conduction band profile we show that this
      observation can be explained by reduced leakage of electrons from the Schottky
      gates into the semiconductor through the Schottky barrier, consistent with the
      effect of "bias cooling." Upon noise reduction, the noise power spectrum
      generally changes from Lorentzian to 1/f type. By comparing wafers with different
      Al content, we exclude that DX centers play a dominant role in the charge noise.

PMID- 19113502
TI  - Quantum Hall to insulator transition in the bilayer quantum Hall ferromagnet.
AB  - We describe a phase transition of the bilayer quantum Hall ferromagnet at nu=1.
      In the presence of static disorder (modeled by a periodic potential), bosonic
      S=1/2 spinons undergo a superfluid-insulator transition while preserving
      ferromagnetism. The Mott insulating phase has an emergent U(1) photon, and the
      transition is between Higgs and Coulomb phases of this photon. Consequences for
      charge and counterflow conductivity and for interlayer tunneling conductance are
      discussed.

PMID- 19113503
TI  - Tomography of many-body weak values: Mach-Zehnder interferometry.
AB  - We propose and study a weak value (WV) protocol in the context of a solid state
      setup, specifically, an electronic Mach-Zehnder interferometer. This is the first
      specific proposal to measure both the real and imaginary part (i.e., complete
      tomography) of a WV. We also analyze the manifestation of many-body physics in
      the WV to be measured, including finite temperature and shot-noise-like
      contributions.

PMID- 19113504
TI  - Many-body localization study in low-density electron gases: do metals exist in
      two dimensions?
AB  - Using a combination of ground state quantum Monte Carlo and finite size scaling
      techniques, we perform a systematic study of the effect of Coulomb interaction on
      the localization length of a disordered two-dimensional electron gas. We find
      that correlations delocalize the 2D system. In the absence of valley degeneracy
      (as in GaAs heterostructures), this delocalization effect corresponds to a finite
      increase of the localization length. The delocalization is much more dramatic in
      the presence of valley degeneracy [as in Si metal-oxide-semiconductor field
      effect transistors], where the localization length increases drastically. We find
      that a simple mechanism accounts for the main features of the metallic behavior
      observed in two-dimensional gases. Our findings support the claim that this
      behavior is a genuine effect of the presence of interactions, yet that the system
      is not a "true" metal in the thermodynamic sense.

PMID- 19113505
TI  - Pseudomagnetic fields and ballistic transport in a suspended graphene sheet.
AB  - We study a suspended graphene sheet subject to the electric field of a gate
      underneath. We compute the elastic deformation of the sheet and the corresponding
      effective gauge field, which modifies the electronic transport. In a clean system
      the two-terminal conductance of the sample is reduced below the ballistic limit
      and is almost totally suppressed at low carrier concentrations in samples under
      tension. Residual disorder restores a small finite conductivity.

PMID- 19113506
TI  - Spin relaxation in quantum dots due to electron exchange with leads.
AB  - We calculate spin relaxation rates in lateral quantum dot systems due to electron
      exchange between dots and leads. Using rate equations, we develop a theoretical
      description of the experimentally observed electric current in the spin blockade
      regime of double quantum dots. A single expression fits the entire current
      profile and describes the structure of both the conduction peaks and the
      suppressed ("valley") region. Extrinsic rates calculated here have to be taken
      into account for accurate extraction of intrinsic relaxation rates due to the
      spin-orbit and hyperfine spin scattering mechanisms from spin blockade
      measurements.

PMID- 19113507
TI  - Stimulated emission of surface plasmon polaritons.
AB  - We have observed laserlike emission of surface plasmon polaritons (SPPs)
      decoupled to the glass prism in an attenuated total reflection setup. SPPs were
      excited by optically pumped molecules in a polymeric film deposited on the top of
      a silver film. Stimulated emission was characterized by a distinct threshold in
      the input-output dependence and narrowing of the emission spectrum. The observed
      stimulated emission and corresponding compensation of the metallic absorption
      loss by gain enables many applications of metamaterials and nanoplasmonic
      devices.

PMID- 19113508
TI  - Fock-Darwin-like quantum dot states formed by charged Mn interstitial ions.
AB  - We report a method of creating electrostatically induced quantum dots by thermal
      diffusion of interstitial Mn ions out of a p-type (GaMn)As layer into the
      vicinity of a GaAs quantum well. This approach creates deep, approximately
      circular, and strongly confined dotlike potential minima in a large (200 microm)
      mesa diode structure without need for advanced lithography or electrostatic
      gating. Magnetotunneling spectroscopy of an individual dot reveals the symmetry
      of its electronic eigenfunctions and a rich energy level spectrum of Fock-Darwin
      like states with an orbital angular momentum component |lz| from 0 to 11.

PMID- 19113509
TI  - Quantum dot spectroscopy using cavity quantum electrodynamics.
AB  - We show how cavity quantum electrodynamics using a tunable photonic crystal
      nanocavity in the strong-coupling regime can be used for single quantum dot
      spectroscopy. From the distinctive avoided crossings observed in the strongly
      coupled system we can identify the neutral and single positively charged exciton
      as well as the biexciton transitions. Moreover we are able to investigate the
      fine structure of those transitions and to identify a novel cavity mediated
      mixing of bright and dark exciton states, where the hyperfine interactions with
      lattice nuclei presumably play a key role. These results are enabled by a
      deterministic coupling scheme which allowed us to achieve unprecedented coupling
      strengths in excess of 150 microeV.

PMID- 19113510
TI  - Nonequilibrium effective vector potential due to pseudospin exchange in graphene.
AB  - We show that exchange interactions in two-dimensional electron gases out of
      equilibrium can generate a fictitious vector potential with intriguing signatures
      in interference and Hall measurements. Detailed predictions are made for
      graphene, where the effect is enhanced by pseudospin exchange.

PMID- 19113511
TI  - Spin-selective Aharonov-Bohm oscillations in a lateral triple quantum dot.
AB  - We present a theory of spin-selective Aharonov-Bohm oscillations in a lateral
      triple quantum dot. We show that to understand the Aharonov-Bohm (AB) effect in
      an interacting electron system within a triple quantum dot molecule (TQD) where
      the dots lie in a ring configuration requires one to not only consider electron
      charge but also spin. Using a Hubbard model supported by microscopic calculations
      we show that, by localizing a single electron spin in one of the dots, the
      current through the TQD molecule depends not only on the flux but also on the
      relative orientation of the spin of the incoming and localized electrons. AB
      oscillations are predicted only for the spin singlet electron complex resulting
      in a magnetic field tunable "spin valve."

PMID- 19113512
TI  - Controlled vaporization of the superconducting condensate in cuprate
      superconductors by femtosecond photoexcitation.
AB  - We use ultrashort intense laser pulses to study superconducting state
      vaporization dynamics in La2-xSrxCuO4 (x=0.1 and 0.15) on the femtosecond time
      scale. We find that the energy density required to vaporize the superconducting
      state is 2.0+/-0.8 and 2.6+/-1.0 K/Cu for x=0.1 and 0.15, respectively. This is
      significantly greater than the condensation energy density, indicating that the
      quasiparticles share a large amount of energy with the boson glue bath on this
      time scale. Considering in detail both spin and lattice energy relaxation
      pathways which take place on the relevant time scale of approximately 10(-12) s,
      the experiments appear to favor phonon-mediated pair-breaking mechanisms over
      spin-mediated pair breaking.

PMID- 19113513
TI  - Evidence for a competition between the superconducting state and the pseudogap
      state of (BiPb)2(SrLa)2CuO6+delta from muon spin rotation experiments.
AB  - The in-plane magnetic penetration depth lambda ab in optimally doped
      (BiPb)2(SrLa)2CuO6+delta (OP Bi2201) was studied by means of muon-spin rotation.
      The measurements of lambda ab(-2)(T) are inconsistent with a simple model of a d
      wave order parameter and a uniform quasiparticle weight around the Fermi surface.
      The data are well described assuming the angular gap symmetry obtained in ARPES
      experiments [Phys. Rev. Lett. 98, 267004 (2007)], which suggest that the
      superconducting gap in OP Bi2201 exists only in segments of the Fermi surface
      near the nodes. The remaining parts of the Fermi surface, which are strongly
      affected by the pseudogap state, do not contribute significantly to the
      superconducting condensate.

PMID- 19113514
TI  - Determination of the superconductor-insulator phase diagram for one-dimensional
      wires.
AB  - We establish the superconductor-insulator phase diagram for quasi-one-dimensional
      wires by measuring a large set of MoGe nanowires. This diagram is roughly
      consistent with the Chakravarty-Schmid-Bulgadaev phase boundary, namely, with the
      critical resistance being equal to RQ=h/4e2. Deviations from this boundary for a
      small fraction of the samples prompt us to suggest an alternative phase diagram,
      which matches the data exactly. Transport properties of wires in the
      superconducting phase are dominated by phase slips, whereas insulating nanowires
      exhibit a weak Coulomb blockade behavior.

PMID- 19113515
TI  - Screening of point charge impurities in highly anisotropic metals: application to
      mu+-spin relaxation in underdoped cuprate superconductors.
AB  - We calculate the screening charge density distribution due to a point charge,
      such as that of a positive muon (mu+), placed between the planes of a highly
      anisotropic layered metal. In underdoped hole cuprates the screening charge
      converts the charge density in the metallic-plane unit cells in the vicinity of
      the mu+ to nearly its value in the insulating state. The current-loop-ordered
      state observed by polarized neutron diffraction then vanishes in such cells, and
      also in nearby cells over a distance of order the intrinsic correlation length of
      the loop-ordered state. This strongly suppresses the magnetic field at the mu+
      site. We estimate this suppressed field in underdoped YBa2Cu3O6+x and La2
      xSrxCuO4, and find consistency with the observed approximately 0.2 G field in the
      former case and the observed upper bound of approximately 0.2 G in the latter
      case. This resolves the controversy between the neutron diffraction and mu-spin
      relaxation experiments.

PMID- 19113516
TI  - Effective theory of magnetization plateaux in the Shastry-Sutherland lattice.
AB  - We use the nonperturbative Contractor-Renormalization method (CORE) in order to
      derive an effective model for triplet excitations on the Shastry-Sutherland
      lattice. For strong enough magnetic fields, various magnetization plateaux are
      observed, e.g., at 1/8, 1/4, 1/3 of the saturation, as found experimentally in a
      related compound. Moreover, other stable plateaux are found at 1/9, 1/6, or 2/9.
      We give a critical review of previous works and try to resolve some apparent
      inconsistencies between various theoretical approaches.

PMID- 19113517
TI  - Evidence for a spin emulsion.
AB  - Magnetic small-angle neutron scattering from the itinerant electron magnet, Y(Mn1
      xFex)2, in which ferromagnetic and antiferromagnetic spin correlations compete,
      is found to follow an anomalous Q(-6) dependence (Q = 4pisintheta/lambda). It is
      suggested that this scattering is the magnetic analogue of that predicted for a
      structural microemulsion by Teubner's extension of conventional Kirste-Porod
      scattering to well-defined interfaces with extreme differences between mean and
      Gaussian curvatures. The "spin-emulsion-like" morphology of magnetic interfaces
      in Y(Mn1-xFex)2 is confirmed both qualitatively and quantitatively by a simple
      model based upon reported near neighbor Mn and Fe spin correlations.

PMID- 19113518
TI  - Intershell exchange and sequential electrically injected spin populations of InAs
      quantum-dot shell states.
AB  - We report sequential spin population of individual shell states of self-assembled
      InAs quantum dots controlled by a spin-polarized current from an Fe contact, and
      determine the s-p and p-d intershell exchange energies. We resolve excitonic
      features in the electroluminescence (EL) spectra associated with individual
      quantum levels. In contrast with simple models of shell occupation, the EL
      circular polarization exhibits maxima shifted with respect to the intensity
      peaks. Calculations show that this is due to intershell exchange. Exchange
      energies for the s-p and p-d shells are 7+/-2 and 13.5+/-1 meV, respectively.

PMID- 19113519
TI  - Dynamic spin ice: Pr2Sn2O7.
AB  - In this Letter, we report a new spin ice--Pr2Sn2O7--which appears to have
      enhanced residual entropy due to the dynamic nature of the spins. Neutron
      scattering experiments show that at 200 mK, there is a significant amount of
      magnetic diffuse scattering which can be fit to the dipolar spin-ice model.
      However, these short-ranged ordered spins have a quasielastic response that is
      atypical of the canonical spin ices, and suggests that the ground state is
      dynamic (i.e., composed of locally ordered two-in-two-out spin configurations
      that can tunnel between energetically equivalent orientations). We report this as
      an example of a dynamic spin ice down to 200 mK.

PMID- 19113520
TI  - Anisotropic three-dimensional magnetism in CaFe2As2.
AB  - Inelastic neutron scattering measurements of the magnetic excitations in CaFe2As2
      indicate that the spin wave velocity in the Fe layers is exceptionally large and
      similar in magnitude to the cuprates. However, the spin wave velocity
      perpendicular to the layers is at least half as large that in the layer, so that
      the magnetism is more appropriately categorized as anisotropic three-dimensional,
      in contrast to the two-dimensional cuprates. Exchange constants derived from band
      structure calculations predict spin wave velocities that are consistent with the
      experimental data.

PMID- 19113521
TI  - Single charged quantum dot in a strong optical field: absorption, gain, and the
      ac-Stark effect.
AB  - We investigate a singly charged quantum dot under a strong optical driving field
      by probing the system with a weak optical field. We observe all critical features
      predicted by Mollow for a strongly driven two-level atomic system in this solid
      state nanostructure, such as absorption, the ac-Stark effect, and optical gain.
      Our results demonstrate that even at high optical field strengths the electron in
      a single quantum dot with its dressed ground state and trion state behaves as a
      well-isolated two-level quantum system.

PMID- 19113522
TI  - Charge order in LuFe2O4: antiferroelectric ground state and coupling to
      magnetism.
AB  - X-ray scattering by multiferroic LuFe2O4 is reported. Below 320 K, superstructure
      reflections indicate an incommensurate charge order with propagation close to
      (1/3 1/3 3/2). The corresponding charge configuration, also found by electronic
      structure calculations as most stable, contains polar Fe/O double layers with
      antiferroelectric stacking. Diffuse scattering at 360 K, with (1/3 1/3 0)
      propagation, indicates ferroelectric short-range correlations between neighboring
      double layers. The temperature dependence of the incommensuration indicates that
      charge order and magnetism are coupled.

PMID- 19113523
TI  - Charge order, dynamics, and magnetostructural transition in multiferroic LuFe2O4.
AB  - We investigated the series of temperature and field-driven transitions in LuFe2O4
      by optical and Mossbauer spectroscopies, magnetization, and x-ray scattering in
      order to understand the interplay between charge, structure, and magnetism in
      this multiferroic material. We demonstrate that charge fluctuation has an onset
      well below the charge ordering transition, supporting the "order by fluctuation"
      mechanism for the development of charge order superstructure. Bragg splitting and
      large magneto-optical contrast suggest a low-temperature monoclinic distortion
      that can be driven by both temperature and magnetic field.

PMID- 19113524
TI  - Abrupt transition from a free, repulsive to a condensed, attractive DNA phase,
      induced by multivalent polyamine cations.
AB  - We have investigated the energetics of DNA condensation by multivalent polyamine
      cations. Solution small angle x-ray scattering was used to monitor interactions
      between short 25 base pair dsDNA strands in the free supernatant DNA phase that
      coexists with the condensed DNA phase. Interestingly, when tetravalent spermine
      is used, significant inter-DNA repulsion is observed in the free phase, in
      contrast with the presumed inter-DNA attraction in the coexisting condensed
      phase. DNA condensation thus appears to be a discrete, first-order-like,
      transition from a repulsive gaseous to an attractive condensed solid phase, in
      accord with the reported all-or-none condensation of giant DNA. We further
      quantify the electrostatic repulsive potentials in the free DNA phase and
      estimate the number of additional spermine cations that bind to DNA upon
      condensation.

PMID- 19113525
TI  - Comment on "Possible observation of phase separation near a quantum phase
      transition in doubly connected ultrathin superconducting cylinders of aluminum".

PMID- 19113527
TI  - Local interactions and non-abelian quantum loop gases.
AB  - Two-dimensional quantum loop gases are elementary examples of topological ground
      states with Abelian or non-Abelian anyonic excitations. While Abelian loop gases
      appear as ground states of local, gapped Hamiltonians such as the toric code, we
      show that gapped non-Abelian loop gases require nonlocal interactions (or
      nontrivial inner products). Perturbing a local, gapless Hamiltonian with an
      anticipated "non-Abelian" ground-state wave function immediately drives the
      system into the Abelian phase, as can be seen by measuring the Hausdorff
      dimension of loops. Local quantum critical behavior is found in a loop gas in
      which all equal-time correlations of local operators decay exponentially.

PMID- 19113528
TI  - Adiabatic nonlinear probes of one-dimensional bose gases.
AB  - We discuss two complimentary problems: adiabatic loading of one-dimensional
      bosons into an optical lattice and merging two one-dimensional Bose systems. Both
      problems can be mapped to the sine-Gordon model. This mapping allows us to find
      power-law scalings for the number of excitations with the ramping rate in the
      regime where the conventional linear response approach fails. We show that the
      exponent of this power law is sensitive to the interaction strength. In
      particular, the response is larger, or less adiabatic, for strongly (weakly)
      interacting bosons for the loading (merging) problem. Our results illustrate that
      in general the nonlinear response to slow relevant perturbations can be a
      powerful tool for characterizing properties of interacting systems.

PMID- 19113529
TI  - Locally optimal control of quantum systems with strong feedback.
AB  - For quantum systems with high purity, we find all observables that, when
      continuously monitored, maximize the instantaneous reduction in the average
      linear entropy. This allows us to obtain all locally optimal feedback protocols
      with strong feedback, and explicit expressions for the best such protocols for
      systems of size N < or =4. We also show that for a qutrit the locally optimal
      protocol is the optimal protocol for observables with equispaced eigenvalues,
      providing the first fully optimal feedback protocol for a 3-state system.

PMID- 19113530
TI  - Naimark-dilated PT-symmetric brachistochrone.
AB  - The quantum mechanical brachistochrone system with a PT-symmetric Hamiltonian is
      Naimark-dilated and reinterpreted as a subsystem of a Hermitian system in a
      higher-dimensional Hilbert space. This opens a way to a direct experimental
      implementation of the recently hypothesized PT-symmetric ultrafast
      brachistochrone regime of Bender et al. [Phys. Rev. Lett. 98, 040403 (2007)] in
      an entangled two-spin system.

PMID- 19113531
TI  - Coulomb breakup problem.
AB  - We formulate scattering theory in the framework of a surface-integral approach
      utilizing analytically known asymptotic forms of the three-body wave functions.
      This formulation is valid for both short-range and Coulombic potentials. The post
      and prior forms of the breakup amplitude are derived without any reference to
      renormalization procedures.

PMID- 19113532
TI  - Generation of quantum-dot cluster States with a superconducting transmission line
      resonator.
AB  - We propose an efficient method to generate cluster states in spatially separated
      double quantum dots with a superconducting transmission line resonator. When the
      detuning between the double-dot qubit transition frequency and the frequency of
      the full wave mode in the transmission line resonator satisfies some conditions,
      an Ising-like operator between an arbitrary two separated qubits can be achieved.
      Even including the main noise sources, it is shown that the high fidelity cluster
      states could be generated in this solid system in just one step.

PMID- 19113533
TI  - Perfect state transfer on a spin chain without state initialization.
AB  - We demonstrate that perfect state transfer can be achieved using an engineered
      spin chain and clean local end-chain operations, without requiring the
      initialization of the state of the medium nor fine-tuning of control pulses. This
      considerably relaxes the prerequisites for obtaining reliable transfer of quantum
      information across interacting-spin systems. Moreover, it allows us to shed light
      on the interplay among purity, entanglement, and operations on a class of many
      body systems potentially useful for quantum information processing tasks.

PMID- 19113534
TI  - Driving-induced crossover: from classical criticality to self-organized
      criticality.
AB  - We propose a spin model with quenched disorder which exhibits in slow driving two
      drastically different types of critical nonequilibrium steady states. One of them
      corresponds to classical criticality requiring fine-tuning of the disorder. The
      other is a self-organized criticality which is insensitive to disorder. The
      crossover between the two types of criticality is determined by the mode of
      driving. As one moves from "soft" to "hard" driving the universality class of the
      critical point changes from a classical order-disorder to a quenched Edwards
      Wilkinson universality class. The model is viewed as prototypical for a broad
      class of physical phenomena ranging from magnetism to earthquakes.

PMID- 19113535
TI  - Khinchin theorem and anomalous diffusion.
AB  - A recent Letter [M. H. Lee, Phys. Rev. Lett. 98, 190601 (2007)] has called
      attention to the fact that irreversibility is a broader concept than ergodicity,
      and that therefore the Khinchin theorem [A. I. Khinchin, (Dover, New York, 1949)]
      may fail in some systems. In this Letter we show that for all ranges of normal
      and anomalous diffusion described by a generalized Langevin equation the Khinchin
      theorem holds.

PMID- 19113536
TI  - Combination of BLOCH oscillations with a Ramsey-Borde interferometer: new
      determination of the fine structure constant.
AB  - We report a new experimental scheme which combines atom interferometry with Bloch
      oscillations to provide a new measurement of the ratio h/mRb. By using Bloch
      oscillations, we impart to the atoms up to 1600 recoil momenta and thus we
      improve the accuracy on the recoil velocity measurement. The deduced value of
      h/mRb leads to a new determination of the fine structure constant alpha(-1)
      =137.03599945 (62) with a relative uncertainty of 4.6 x 10(-9). The comparison of
      this result with the value deduced from the measurement of the electron anomaly
      provides the most stringent test of QED.

PMID- 19113537
TI  - Neutron reactions in accreting neutron stars: a new pathway to efficient crust
      heating.
AB  - In our calculation of neutron star crust heating we include several key new model
      features. In earlier work electron capture (EC) only allowed neutron emission
      from the daughter ground state; here we calculate, in a deformed quasi-random
      phase approximation (QRPA) model, EC decay rates to all states in the daughter
      that are allowed by Gamow-Teller selection rules and energetics. The subsequent
      branching ratios between the 1n,...,xn channels and the competing gamma decay are
      calculated in a Hauser-Feshbach model. In our multicomponent plasma model a
      single (EC, xn) reaction step can produce several neutron-deficient nuclei, each
      of which can further decay by (EC, xn). Hence, the neutron emission occurs more
      continuously with increasing depth as compared to that in a one-component plasma
      model.

PMID- 19113538
TI  - Dark-matter particles without weak-scale masses or weak interactions.
AB  - We propose that dark matter is composed of particles that naturally have the
      correct thermal relic density, but have neither weak-scale masses nor weak
      interactions. These models emerge naturally from gauge-mediated supersymmetry
      breaking, where they elegantly solve the dark-matter problem. The framework
      accommodates single or multiple component dark matter, dark-matter masses from 10
      MeV to 10 TeV, and interaction strengths from gravitational to strong. These
      candidates enhance many direct and indirect signals relative to weakly
      interacting massive particles and have qualitatively new implications for dark
      matter searches and cosmological implications for colliders.

PMID- 19113540
TI  - Is the spectrum of highly excited mesons purely coulombian?
AB  - We show that a static central potential may provide a precise description of
      highly excited light unflavored mesons. Because of string breaking, this
      potential becomes of chromoelectric type at sufficiently large quark-antiquark
      distances giving rise to a Coulombian spectrum. The same conclusion can be
      inferred for any other meson sector through a straightforward extension of our
      analysis.

PMID- 19113539
TI  - Evidence for neutral B meson decays to omegaK*0.
AB  - We present the results of a study of the charmless vector-vector decay B0-
      >omegaK*0 with 657 x 10(6) BB pairs collected with the Belle detector at the KEKB
      e+e- collider. We measure the branching fraction to be B(B0-->omegaK*0) = [1.8+/
      0.7(stat)+/-0.3(syst)]x 10(-6) with 3.0sigma significance. We also perform a
      helicity analysis of the omega and K*0 vector mesons, and obtain the longitudinal
      polarization fraction fL(B0-->omegaK*0) = 0.56+/-0.29(stat) -0.08(+0.18)(syst).
      Finally, we measure a large nonresonant branching fraction B[B0-->omegaK+pi(-);M
      Kpi in(0.755,1.250) GeV/c2] = [5.1+/-0.7(stat)+/-0.7(syst)]x 10(-6) with a
      significance of 9.5sigma.

PMID- 19113543
TI  - Strong-field tunneling without ionization.
AB  - In the tunneling regime of strong laser field ionization we measure a substantial
      fraction of neutral atoms surviving the laser pulse in excited states. The
      measured excited neutral atom yield extends over several orders of magnitude as a
      function of laser intensity. Our findings are compatible with the strong-field
      tunneling-plus-rescattering model, confirming the existence of a widely
      unexplored neutral exit channel (frustrated tunneling ionization). Strong
      experimental support for this mechanism as origin of excited neutral atoms stems
      from the dependence of the excited neutral yield on the laser ellipticity, which
      is as expected for a rescattering process. Theoretical support for the proposed
      mechanism comes from the agreement of the neutral excited state distribution
      centered at n = 6-10 obtained from both, a full quantum mechanical and a
      semiclassical calculation, in agreement with the experimental results.

PMID- 19113544
TI  - Inelastic collisions in optically trapped ultracold metastable ytterbium.
AB  - We report measurement of inelastic loss in dense and cold metastable ytterbium
      (Yb[3P2]). Use of an optical far-off-resonance trap enables us to trap atoms in
      all magnetic sublevels, removing m-changing collisional trap loss from the
      system. Trapped samples of Yb[3P2] are produced at a density of 2 x 10(13) cm(-3)
      and temperature of 2 microK. We observe rapid two-body trap loss of Yb[3P2] and
      measure the inelastic collision rate constant 1.0(3) x 10(-11) cm3 s(-1). The
      existence of the fine-structure changing collisions between atoms in the 3P2
      state is strongly suggested.

PMID- 19113545
TI  - Classical trajectory diagnosis of a fingerlike pattern in the correlated electron
      momentum distribution in strong field double ionization of helium.
AB  - With a semiclassical quasistatic model, we identify the distinct roles of nuclear
      Coulomb attraction, final-state electron repulsion, and the electron-field
      interaction in forming the fingerlike (or V-shaped) pattern in the correlated
      electron momentum distribution for helium double ionization in intense laser
      field [Phys. Rev. Lett. 99, 263002;Phys.Rev.Lett.99, 263003 (2007)]. The
      underlying microscopic trajectory configurations responsible for asymmetric
      electron energy sharing after electron-electron collision have been uncovered,
      and the corresponding subcycle dynamics is analyzed. The correlation pattern is
      found to be sensitive to the transverse momentum of correlated electrons.

PMID- 19113546
TI  - Laser-intensity dependent vibrational excitation and alignment of molecular ions
      in the ultrafast multiphoton regime.
AB  - H2 molecules were ionized in the ultrafast (approximately 150 fs) multiphoton
      regime (263 nm, approximately 10(13) W cm(-2)). Earlier experiments investigated
      the kinetic energies of electrons or ions only. Using a unique experiment, we
      show that the vibrational excitation of molecular ions contains essential
      information about the dynamics of the process. In addition, we prove some earlier
      interpretations wrong. A realistic model based on vibronically excited
      intermediates, Stark shifting into resonance, reproduces the measurements,
      demonstrating that resonances continue to be important in the femtosecond regime.
      This eventually enables ultrafast control of the vibrational excitation of
      molecular ions, which is relevant to the whole field of molecular physics and
      physical chemistry.

PMID- 19113547
TI  - Differential cross sections for the ionization of oriented H2 molecules by
      electron impact.
AB  - A nonperturbative close-coupling technique is used to calculate differential
      cross sections for the electron-impact ionization of H2 at an energy of 35.4 eV.
      Our approach allows cross sections for any orientation of the molecule with
      respect to the incident electron beam to be analyzed. New features in the
      resulting cross sections are found compared with the case where the molecular
      orientation is averaged, and also with cross sections for He at equivalent
      electron kinematics. When averaged over all possible molecular orientations, good
      agreement is found with recent experimental results.

PMID- 19113548
TI  - Is CO carbon KVV Auger electron emission affected by the photoelectron?
AB  - Angular distributions (ADs) of O+ fragments from C 1s photoexcited CO detected in
      coincidence with carbon KVV Auger electrons emitted in the horizontal direction
      were measured at photon energies of 298, 305, 320, and 450 eV. At 450 eV, the ADs
      are polarization-independent and coincide with the molecular-frame Auger electron
      angular distribution. All measured ADs can be rationalized as a product of the
      same molecular-frame Auger electron angular distribution and the axial
      selectivity in the photoionization process. Thus the interaction between the
      photoelectron and the Auger electron for the normal Auger decay of CO can be
      neglected, and the two-step model is a good approximation.

PMID- 19113549
TI  - Rotational study of carbon monoxide solvated with helium atoms.
AB  - High resolution microwave and millimeter-wave spectra of HeN-CO clusters with N
      up to 10, produced in a molecular expansion, were observed. Two series of J = 1-0
      transitions were detected, which correspond to the a-type and b-type J = 1-0
      transitions of He1-CO. The B rotational constant initially decreases with N and
      reaches a minimum at N = 3. Its subsequent rise indicates the transition from a
      molecular complex to a quantum solvated system already for N = 4. For N > or =6,
      the B value becomes larger than that of He1-CO, indicating an almost free
      rotation of CO within the helium environment.

PMID- 19113550
TI  - Transforming spatial entanglement using a domain-engineering technique.
AB  - We study the spatial correlation of a two-photon entangled state produced in a
      multistripe periodically poled LiTaO3 crystal by spontaneous parametric down
      conversion. The far-field diffraction-interference experiments reveal that the
      transverse modulation of domain patterns transforms the spatial mode function of
      the two-photon state. This result offers an approach to prepare a novel type of
      two-photon state with a unique spatial entanglement by using a domain-engineering
      technique.

PMID- 19113551
TI  - Phase-sensitive manipulations of a squeezed vacuum field in an optical parametric
      amplifier inside an optical cavity.
AB  - A squeezed vacuum field can be amplified or deamplified when it is injected, as
      the signal beam, into a phase-sensitive optical parametric amplifier (OPA) inside
      an optical cavity. The spectral features of the reflected quantized signal field
      are controlled by the relative phase between the injected squeezed vacuum field
      and the pump field for the OPA. The experimental results demonstrate coherent
      phenomena of OPA in the quantum regime and show phase-sensitive manipulations of
      quantum fluctuations for quantum information processing.

PMID- 19113552
TI  - Even-order aberration cancellation in quantum interferometry.
AB  - We report the first experimental demonstration of even-order aberration
      cancellation in quantum interferometry. The effect is a spatial counterpart of
      the spectral group velocity dispersion cancellation, which is associated with
      spectral entanglement. It is manifested in temporal interferometry by virtue of
      the multiparameter spatial-spectral entanglement. Spatially entangled photons,
      generated by spontaneous parametric down-conversion, were subjected to spatial
      aberrations introduced by a deformable mirror that modulates the wave front. We
      show that only odd-order spatial aberrations affect the quality of quantum
      interference.

PMID- 19113542
TI  - Suppression pattern of neutral pions at high transverse momentum in Au + Au
      collisions at sqrt[sNN]=200 GeV and constraints on medium transport coefficients.
AB  - For Au + Au collisions at 200 GeV, we measure neutral pion production with good
      statistics for transverse momentum, pT, up to 20 GeV/c. A fivefold suppression is
      found, which is essentially constant for 5 < pT < 20 GeV/c. Experimental
      uncertainties are small enough to constrain any model-dependent parametrization
      for the transport coefficient of the medium, e.g., q in the parton quenching
      model. The spectral shape is similar for all collision classes, and the
      suppression does not saturate in Au + Au collisions.

PMID- 19113553
TI  - Measurement of sub-shot-noise correlations of spatial fluctuations in the photon
      counting regime.
AB  - We have measured sub-shot-noise quantum correlations of spatial fluctuations in
      the far-field image of the parametric fluorescence created in a type I beta
      barium-borate nonlinear crystal. Imaging is performed at very low light level
      (0.15 photons per pixel) with an electron multiplying charge coupled device
      camera. Experimental results overcome the standard quantum limit shot-noise level
      without subtraction of the variance of the detection noise.

PMID- 19113554
TI  - Generation of large-amplitude coherent-state superposition via ancilla-assisted
      photon subtraction.
AB  - We propose and demonstrate a novel method to generate a large-amplitude coherent
      state superposition (CSS) via ancilla-assisted photon subtraction. The ancillary
      mode induces quantum interference of indistinguishable processes in an extended
      space, widening the controllability of quantum superposition at the conditional
      output. We demonstrate this by a simple time-separated two-photon subtraction
      from continuous wave squeezed light. We observe the largest CSS of traveling
      light ever reported without correcting any imperfections, which will enable
      various quantum information applications with CSS states.

PMID- 19113541
TI  - Observation of the doubly strange b baryon Omegab-.
AB  - We report the observation of the doubly strange b baryon Omegab- in the decay
      channel Omegab(-)-->J/psiOmega-, with J/psi-->mu+mu(-) and Omega(-)-->LambdaK(-)-
      >(ppi-)K-, in pp collisions at sqrt[s]=1.96 TeV. Using approximately 1.3 fb(-1)
      of data collected with the D0 detector at the Fermilab Tevatron Collider, we
      observe 17.8+/-4.9(stat)+/-0.8(syst) Omegab- signal events at a mass of 6.165+/
      0.010(stat)+/-0.013(syst) GeV. The significance of the observed signal is
      5.4sigma, corresponding to a probability of 6.7 x 10(-8) of it arising from a
      background fluctuation.

PMID- 19113555
TI  - Three-dimensional coherent optical waves localized on trochoidal parametric
      surfaces.
AB  - We theoretically demonstrate that the three-dimensional (3D) coherent laser waves
      formed by the degenerate Laguerre-Gaussian modes with different longitudinal
      indices are well localized on rotating trochoidal parametric surfaces. We further
      use a large-Fresnel-number laser system to realize the existence of the laser
      modes related to trochoidal coherent states. Experimental results reveal that the
      exotic laser modes generally originate from a superposition of two degenerate
      standing-wave trochoidal coherent states.

PMID- 19113556
TI  - Active control of rogue waves for stimulated supercontinuum generation.
AB  - We demonstrate that rogue waves provide a powerful tool to actively control a
      nonlinear system with minimal effort. Specifically, optical rogue waves--rare,
      bright flashes of broadband light arising in subthreshold supercontinuum
      generation--are initiated by an exceedingly weak stimulus. Using this effect, we
      produce an optically switchable, ultrastable, and bright supercontinuum with
      greatly enhanced coherence.

PMID- 19113557
TI  - Molecular dynamics of extreme mass segregation in a rapidly collapsing bubble.
AB  - A molecular dynamic simulation of a mixture of light and heavy gases in a rapidly
      imploding sphere exhibits virtually complete segregation. The lighter gas
      collects at the focus of the sphere and reaches a temperature that is several
      orders of magnitude higher than when its concentration is 100%. Implosion
      parameters are chosen via a theoretical fit to an observed sonoluminescing bubble
      with an extreme expansion ratio (25:1) of maximum to ambient radii.

PMID- 19113558
TI  - Nonaxisymmetric shapes of a magnetically levitated and spinning water droplet.
AB  - The shape of a weightless spinning liquid droplet is governed by the balance
      between the surface tension and centrifugal forces. The axisymmetric shape for
      slow rotation becomes unstable to a nonaxisymmetric distortion above a critical
      angular velocity, beyond which the droplet progresses through a series of 2-lobed
      shapes. Theory predicts the existence of a family of 3- and 4-lobed equilibrium
      shapes at higher angular velocity. We investigate the formation of a triangular
      shaped magnetically levitated water droplet, driven to rotate by the Lorentz
      force on an ionic current within the droplet. We also study equatorial traveling
      waves which give the droplet threefold, fourfold, and fivefold symmetry.

PMID- 19113560
TI  - Convective dust clouds driven by thermal creep in a complex plasma.
AB  - Steady-state clouds of microparticles were observed, levitating in a low
      frequency glow discharge generated in an elongated vertical glass tube. A heated
      ring was attached to the tube wall outside, so that the particles, exhibiting a
      global convective motion, were confined vertically in the region above the
      location of the heater. It is shown that the particle vortices were induced by
      the convection of neutral gas, and the mechanism responsible for the gas
      convection was the thermal creep along the inhomogeneously heated tube walls. The
      phenomenon of thermal creep, which commonly occurs in rarefied gases under the
      presence of thermal gradients, should generally play a substantial role in
      experiments with complex plasmas.

PMID- 19113559
TI  - Volume reflection dependence of 400 GeV/c protons on the bent crystal curvature.
AB  - The trend of volume reflection parameters (deflection angle and efficiency) in a
      bent (110) silicon crystal has been investigated as a function of the crystal
      curvature with 400 GeV/c protons on the H8 beam line at the CERN Super Proton
      Synchrotron. This Letter describes the analysis performed at six different
      curvatures showing that the optimal radius for volume reflection is approximately
      10 times greater than the critical radius for channeling. A strong scattering of
      the beam by the planar potential is also observed for a bend radius close to the
      critical one.

PMID- 19113561
TI  - Observation of ion-cyclotron-frequency mode-conversion flow drive in tokamak
      plasmas.
AB  - Strong toroidal flow (Vphi) and poloidal flow (Vtheta) have been observed in D
      3He plasmas with ion cyclotron range of frequencies (ICRF) mode-conversion (MC)
      heating on the Alcator C-Mod tokamak. The toroidal flow scales with the rf power
      Prf (up to 30 km/s per MW), and is significantly larger than that in ICRF
      minority heated plasmas at the same rf power or stored energy. The central Vphi
      responds to Prf faster than the outer regions, and the Vphi(r) profile is broadly
      peaked for r/a < or =0.5. Localized (0.3 < or = r/a < or =0.5) Vtheta appears
      when Prf > or =1.5 MW and increases with power (up to 0.7 km/s per MW). The
      experimental evidence together with numerical wave modeling suggests a local flow
      drive source due to the interaction between the MC ion cyclotron wave and 3He
      ions.

PMID- 19113563
TI  - Weakly turbulent magnetohydrodynamic waves in compressible low-beta plasmas.
AB  - In this Letter, weak-turbulence theory is used to investigate interactions among
      Alfven waves and fast and slow magnetosonic waves in collisionless low-beta
      plasmas. The wave kinetic equations are derived from the equations of
      magnetohydrodynamics, and extra terms are then added to model collisionless
      damping. These equations are used to provide a quantitative description of a
      variety of nonlinear processes, including parallel and perpendicular energy
      cascade, energy transfer between wave types, "phase mixing," and the generation
      of backscattered Alfven waves.

PMID- 19113562
TI  - Rapid generation of angular momentum in bounded magnetized plasma.
AB  - Direct numerical simulations of two-dimensional decaying MHD turbulence in
      bounded domains show the rapid generation of angular momentum in nonaxisymmetric
      geometries. It is found that magnetic fluctuations enhance this mechanism. On a
      larger time scale, the generation of a magnetic angular momentum, or angular
      field, is observed. For axisymmetric geometries, the generation of angular
      momentum is absent; nevertheless, a weak magnetic field can be observed. The
      derived evolution equations for both the angular momentum and angular field yield
      possible explanations for the observed behavior.

PMID- 19113564
TI  - Observation of resistive and ferritic wall modes in a line-tied pinch.
AB  - The resistive wall mode is experimentally identified and characterized in a line
      tied, cylindrical screw pinch when the edge safety factor is less than a critical
      value. Different wall materials have been used to change the wall time and show
      that the growth rates for the RWM scale with wall time and safety factor as
      expected by theory. The addition of a ferritic wall material outside the
      conducting shell leads to growth rates larger than the observed RWM and larger
      than theoretical predictions for the ferritic wall mode.

PMID- 19113565
TI  - Coherent optical control of the ultrafast dephasing of phonon-plasmon coupling in
      a polar semiconductor using a pulse train of below-band-gap excitation.
AB  - In the investigation of the nonequilibrium ultrafast dynamics of the coherent
      phonon-plasmon coupled modes in a polar semiconductor, we predict theoretically
      that their coherent oscillations can be efficiently controlled by using the pulse
      train of below-band-gap excitation. The dynamics of the coherent modes are driven
      by the virtual electron-hole pairs, which would avoid dephasing sources such as
      accumulation of photoexcited charges and spontaneous emission. This implies that
      carrier mobility can also be efficiently controlled and dramatically enhanced by
      synchronizing the pulse train with the coherent oscillation of the carrier
      relevant coupled mode.

PMID- 19113566
TI  - High thermal conductivity of single polyethylene chains using molecular dynamics
      simulations.
AB  - We use molecular dynamics simulations to calculate the thermal conductivity of
      single polyethylene chains employing both the Green-Kubo approach and a modal
      decomposition method. Although bulk polyethylene is a thermal insulator, our
      results suggest that the thermal conductivity of an individual polymer chain can
      be very high, even divergent in some cases. Our results suggest that polymers can
      be engineered with high thermal conductivity for a wide variety of applications.

PMID- 19113567
TI  - Direct observation of a nonequilibrium electro-osmotic instability.
AB  - We present a visualization of the predicted instability in ionic conduction from
      a binary electrolyte into a charge selective solid. This instability develops
      when a voltage greater than critical is applied to a thin layer of copper sulfate
      flanked by a copper anode and a cation selective membrane. The current-voltage
      dependence exhibits a saturation at the limiting current. With a further increase
      of voltage, the current increases, marking the transition to the overlimiting
      conductance. This transition is mediated by the appearing vortical flow that
      increases with the applied voltage.

PMID- 19113568
TI  - Contrast reversal in atomic-resolution chemical mapping.
AB  - We report an unexpected result obtained using chemical mapping on the new,
      aberration corrected Nion UltraSTEM at Daresbury. Using different energy windows
      above the L2,3 edge in 011 silicon to map the position of the atomic columns we
      find a contrast reversal which produces an apparent and misleading translation of
      the silicon columns. Using simulations of the imaging process, we explain the
      intricate physical mechanisms leading to this effect.

PMID- 19113569
TI  - Alignment-induced epitaxial transition in organic-organic heteroepitaxy.
AB  - We report the epitaxial growth of thin films of a small organic molecule
      (pentacene) on polymer substrates with controllable photoalignment over a wide
      range. The pentacene molecular plane exhibited a distinct orientational change
      from parallel to perpendicular relative to the polymer chain with increasing
      substrate polymer alignment. Each orientation consists of twinlike domains. Such
      characteristics reveal a unique alignment-induced epitaxial transition controlled
      by the subtle balance of weak interactions, showing a promising approach for
      tuning the characteristics of organic semiconductor based electronic devices.

PMID- 19113570
TI  - Ionization energies of shallow donor states in ZnO created by reversible
      formation and depletion of H interstitials.
AB  - The electronic effects of H atoms at interstitial sites in ZnO have been
      investigated by high resolution electron energy loss spectroscopy (HREELS). A
      reversible doping is achieved by exposing single crystalline (0001)-oriented ZnO
      substrates to atomic hydrogen. At low temperatures, interstitial H atoms form
      shallow donor states. At sufficiently high temperatures, the electrons are
      excited into the conduction band. We use EELS to demonstrate the presence of
      plasmons resulting from this finite density of charge carriers in the conduction
      band. Above temperatures of 100 K, a strong, plasmon-induced broadening of the
      quasielastic peak in the HREELS data is observed. The analysis of the temperature
      dependence yields a donor level ionization energy of 25+/-5 meV.

PMID- 19113571
TI  - Orbital mixing and nesting in the bilayer manganites La2-2xSr1+2xMn2O7.
AB  - A first principles study of La2-2xSr1+2xMn2O7 compounds for doping levels 0.3 <
      or = x < or = 0.5 shows that the low energy electronic structure of the majority
      spin carriers is determined by strong momentum-dependent interactions between the
      Mn eg dx2-y2 and d3z2-r2 orbitals, which, in addition to an x-dependent Jahn
      Teller distortion, differ in the ferromagnetic and antiferromagnetic phases. The
      Fermi surface exhibits nesting behavior that is reflected by peaks in the static
      susceptibility, whose positions as a function of momentum have a nontrivial
      dependence on x.

PMID- 19113572
TI  - Reversible phase transformation and doubly charged anions at the surface of
      simple cubic RbC60.
AB  - The simple cubic phase of a RbC60 thin film has been studied using photoelectron
      spectroscopy. The simple cubic-to-dimer transition is found to be reversible at
      the film surface. A sharp Fermi edge is observed and a lower limit of 0.5 eV is
      found for the surface Hubbard U, pointing to a strongly correlated metallic
      character of thin-film simple cubic RbC60. A molecular charge state is identified
      in the valence band and core-level photoemission spectra which arises from C60(2
      ) anions and contributes to the spectral intensity at the Fermi level.

PMID- 19113573
TI  - Spin-orbit coupling in ferromagnetic nickel.
AB  - We use the Gutzwiller variational theory to investigate the electronic and
      magnetic properties of fcc nickel. Our particular focus is on the effects of the
      spin-orbit coupling. Unlike standard relativistic band-structure theories, we
      reproduce the experimental magnetic-moment direction and we explain the change of
      the Fermi-surface topology that occurs when the magnetic-moment direction is
      rotated by an external magnetic field. The Fermi surface in our calculation
      deviates from early de Haas-van Alphen results. We attribute these discrepancies
      to an incorrect interpretation of the raw de Haas-van Alphen data.

PMID- 19113574
TI  - Polarized superfluidity in the attractive hubbard model with population
      imbalance.
AB  - We study a two-component Fermi system with attractive interactions and different
      populations of the two species in a cubic lattice. For an intermediate coupling,
      we find a uniformly polarized superfluid which is stable down to very low
      temperatures. The momentum distribution of this phase closely resembles that of
      the Sarma phase, characterized by two Fermi surfaces. This phase is shown to be
      stabilized by a potential energy gain, as in a BCS superfluid, in contrast with
      the unpolarized Bose-Einstein condensate which is stabilized by kinetic energy.
      We present general arguments suggesting that preformed pairs in the unpolarized
      superfluid favor the stabilization of a polarized superfluid phase.

PMID- 19113575
TI  - Nonequilibrium transport through a point contact in the nu = 5/2 non-Abelian
      quantum Hall state.
AB  - We analyze charge-e/4 quasiparticle tunneling between the edges of a point
      contact in a non-Abelian model of the nu = 5/2 quantum Hall state in the presence
      of a finite voltage difference using the time-dependent density-matrix
      renormalization group method. We confirm that, as the voltage decreases, the
      system is broken into two pieces. In the limits of small and large voltage, we
      recover the results expected from perturbation theory about the infrared and
      ultraviolet fixed points. We test our methods by finding the analogous
      nonequilibrium current through a point contact at nu = 1/3.

PMID- 19113576
TI  - New model system for a one-dimensional electron liquid: self-organized atomic
      gold chains on Ge(001).
AB  - Unique electronic properties of self-organized Au atom chains on Ge(001) in novel
      c(8 x 2) long-range order are revealed by scanning tunneling microscopy. Along
      the nanowires an exceptionally narrow conduction path exists which is virtually
      decoupled from the substrate. It is laterally confined to the ultimate limit of
      single atom dimension, and is strictly separated from its neighbors, as not
      previously reported. The resulting tunneling conductivity shows a dramatic
      inhomogeneity of 2 orders of magnitude. The atom chains thus represent an
      outstandingly close approach to a one-dimensional electron liquid.

PMID- 19113577
TI  - Measurement of temporal correlations of the overhauser field in a double quantum
      dot.
AB  - In quantum dots made from materials with nonzero nuclear spins, hyperfine
      coupling creates a fluctuating effective Zeeman field (Overhauser field) felt by
      electrons, which can be a dominant source of spin qubit decoherence. We
      characterize the spectral properties of the fluctuating Overhauser field in a
      GaAs double quantum dot by measuring correlation functions and power spectra of
      the rate of singlet-triplet mixing of two separated electrons. Away from zero
      field, spectral weight is concentrated below 10 Hz, with approximately 1/f2
      dependence on frequency f. This is consistent with a model of nuclear spin
      diffusion, and indicates that decoherence can be largely suppressed by echo
      techniques.

PMID- 19113578
TI  - Optical spin initialization and nondestructive measurement in a quantum dot
      molecule.
AB  - The spin of an electron in a self-assembled InAs/GaAs quantum dot molecule is
      optically prepared and measured through the trion triplet states. A longitudinal
      magnetic field is used to tune two of the trion states into resonance, forming a
      superposition state through asymmetric spin exchange. As a result, spin-flip
      Raman transitions can be used for optical spin initialization, while separate
      trion states enable cycling transitions for nondestructive measurement. With two
      laser transmission spectroscopy we demonstrate both operations simultaneously,
      something not previously accomplished in a single quantum dot.

PMID- 19113579
TI  - Magnetic field effects in pi-conjugated polymer-fullerene blends: evidence for
      multiple components.
AB  - We studied magnetoconductance (MC) and magnetoelectroluminescence (MEL) in
      organic diodes from blends of pi-conjugated polymers and fullerenes at various
      concentrations, c. The MC response is composed of several components that depend
      on the applied bias voltage and c. A dominant positive low-field (LF) component,
      which also governs the MEL response, dramatically decreases and broadens in the
      blends, thus unraveling a positive high-field and negative LF components. The
      positive MC components are caused by electrostatically bound e-h polaron pairs in
      unblended devices, and charge transfer pairs in the blends, which are dominated
      by two different field-induced spin sublevel mixing mechanisms. In contrast, the
      negative LF response is due to e-e and h-h pairs; this is confirmed by studying
      MC in electron- and hole-unipolar devices, which lack positive MC response.

PMID- 19113580
TI  - Conductance of sidewall-functionalized carbon nanotubes: universal dependence on
      adsorption sites.
AB  - We use density functional theory to study the effect of molecular adsorbates on
      the conductance of metallic carbon nanotubes (CNT). The five molecules considered
      (NO2, NH2, H, COOH, OH) lead to very similar scattering of the electrons. The
      adsorption of a single molecule suppresses one of the two available transport
      channels at the Fermi level while the other is left undisturbed. If more
      molecules are adsorbed on the same sublattice, the remaining open channel may or
      may not be blocked, depending on the relative position of the adsorbates. If the
      relative positions satisfy a simple geometric condition, this channel remains
      fully open independently of the number of adsorbed molecules.

PMID- 19113581
TI  - Lack of evidence for orbital-current effects in the high-temperature Y2Ba4Cu7O15
      delta superconductor using 89Y nuclear magnetic resonance.
AB  - We have performed NMR measurements at the Y site on a c-axis-oriented powder
      sample of the cuprate superconductor Y2Ba4Cu7O15-delta to search for the possible
      orbital-current phase. The temperature dependence of the Y linewidth and
      relaxation behavior in the normal-conducting phase were studied down to 100 K.
      These measurements give upper limits for a static magnetic field and the
      amplitude of a fluctuating magnetic field at the Y site of < or approximately
      0.15 and < or approximately 0.7 mT, respectively. These values provide
      significant constraints on possible static or quasistatic orbital currents.

PMID- 19113582
TI  - Direct observation of the superconducting gap in phonon spectra.
AB  - We show that the superconducting energy gap 2Delta can be directly observed in
      phonon spectra, as predicted by recent theories. In addition, since each phonon
      probes the gap on only a small part of the Fermi surface, the gap anisotropy can
      be studied in detail. Our neutron scattering investigation of the anisotropic
      conventional superconductor YNi2B2C demonstrates this new application of phonon
      spectroscopy.

PMID- 19113583
TI  - High-field pauli-limiting behavior and strongly enhanced upper critical magnetic
      fields near the transition temperature of an arsenic-deficient LaO0.9F0.1FeAs1
      delta superconductor.
AB  - We report upper critical field Bc2(T) data for disordered (arsenic-deficient)
      LaO0.9F0.1FeAs1-delta in a wide temperature and magnetic field range up to 47 T.
      Because of the large linear slope of Bc2 approximately -5.4 to -6.6 T/K near Tc
      approximately 28.5 K, the T dependence of the in-plane Bc2(T) shows a flattening
      near 23 K above 30 T which points to Pauli-limited behavior with Bc2(0)
      approximately 63-68 T. Our results are discussed in terms of disorder effects
      within [corrected] unconventional superconducting pairings.

PMID- 19113584
TI  - Model for the magnetic order and pairing channels in Fe pnictide superconductors.
AB  - A two-orbital model for Fe-pnictide superconductors is investigated using
      computational techniques on two-dimensional square clusters. The hopping
      amplitudes are derived from orbital overlap integrals, or by band structure fits,
      and the spin frustrating effect of the plaquette-diagonal Fe-Fe hopping is
      remarked. A spin striped state is stable in a broad range of couplings in the
      undoped regime, in agreement with neutron scattering. Adding two electrons to the
      undoped ground state of a small cluster, the dominant pairing operators are
      found. Depending on the parameters, two pairing operators were identified: they
      involve inter-xz-yz orbital combinations forming spin singlets or triplets,
      transforming according to the B2g and A2g representations of the D4h group,
      respectively.

PMID- 19113585
TI  - Multiband order parameters for the PrOs4Sb12 and PrRu4Sb12 skutterudite
      superconductors from thermal conductivity measurements.
AB  - Thermal conductivity measurements were performed on single crystal samples of the
      superconducting filled-skutterudite compounds PrOs4Sb12 and PrRu4Sb12 both as a
      function of temperature and transverse magnetic field. In a zero magnetic field,
      the low temperature electronic thermal conductivity of PrRu4Sb12 is consistent
      with a fully gapped Fermi surface. For PrOs4Sb12, residual electronic conduction
      in the zero-temperature limit is consistent with the presence of nodes in the
      superconducting energy gap. The electronic thermal conductivity for both
      compounds shows a rapid rise at low magnetic fields. In PrRu4Sb12, this is
      interpreted in terms of multiband effects. In PrOs4Sb12, we consider the Doppler
      shift of nodal quasiparticles and multiband effects.

PMID- 19113586
TI  - Static magnetic order in Tb2Sn2O7 revealed by muon spin relaxation with exterior
      muon implantation.
AB  - Tb2Sn2O7 has been proposed as an ordered spin ice, but the precise nature of the
      low temperature magnetic state remains uncertain. Recent independent muon spin
      relaxation (microSR) investigations suggest the possibility of exotic ground
      states with static order precluded on time scales longer than 10(-6) s. Here the
      more conventional hypothesis of canted ferromagnetism is tested by means of
      microSR with the muons stopped outside the sample, as well as ultralow field bulk
      magnetization measurements. The field cooled state shows conventional static
      order, while the zero field cooled state may be interpreted in terms of
      conventional closed domains. These results rule out purely dynamical ground
      states and illustrate the value of exterior muon implantation as a complement to
      the conventional technique.

PMID- 19113587
TI  - Carrier-mediated antiferromagnetic interlayer exchange coupling in diluted
      magnetic semiconductor multilayers Ga1-xMnxAs/GaAs:Be.
AB  - We report the antiferromagnetic (AFM) interlayer exchange coupling between
      Ga0.97Mn0.03As ferromagnetic semiconductor layers separated by Be-doped GaAs
      spacers. Polarized neutron reflectivity reveals a characteristic splitting at the
      wave vector corresponding to twice the multilayer period, indicating that the
      coupling between the ferromagnetic layers is AFM. When the applied field is
      increased to above the saturation field, this AFM coupling is suppressed. This
      behavior is not observed when the spacers are undoped, suggesting that the
      observed AFM coupling is mediated by doped charge carriers.

PMID- 19113588
TI  - Probing the spin polarization of current by soft x-ray imaging of current-induced
      magnetic vortex dynamics.
AB  - Time-resolved soft x-ray transmission microscopy is applied to image the current
      induced resonant dynamics of the magnetic vortex core realized in a micron sized
      Permalloy disk. The high spatial resolution better than 25 nm enables us to
      observe the resonant motion of the vortex core. The result also provides the spin
      polarization of the current to be 0.67+/-0.16 for Permalloy by fitting the
      experimental results with an analytical model in the framework of the spin
      transfer torque.

PMID- 19113589
TI  - Influence of the Dzyaloshinskii-Moriya exchange interaction on quantum phase
      interference of spins.
AB  - Magnetization measurements of a Mn12mda wheel single-molecule magnet with a spin
      ground state of S = 7 show resonant tunneling and quantum phase interference,
      which are established by studying the tunnel rates as a function of a transverse
      field applied along the hard magnetization axis. A Dzyaloshinskii-Moriya (DM)
      exchange interaction allows the tunneling between different spin multiplets. It
      is shown that the quantum phase interference of these transitions is strongly
      dependent on the direction of the DM vector.

PMID- 19113590
TI  - Magnetic-field dependence of the YbRh2Si2 Fermi surface.
AB  - Magnetic-field-induced changes of the Fermi surface play a central role in
      theories of the exotic quantum criticality of YbRh2Si2. We have carried out de
      Haas-van Alphen measurements in the magnetic-field range 8 T < or = H < or = 16
      T, and directly observe field dependence of the extremal Fermi surface areas. Our
      data support the theory that a low-field "large" Fermi surface, including the Yb
      4f quasihole, is increasingly spin split until a majority-spin branch undergoes a
      Lifshitz transition and disappears at H0 approximately 10 T, without requiring 4f
      localization at H0.

PMID- 19113591
TI  - Energy equilibration processes of electrons, magnons, and phonons at the
      femtosecond time scale.
AB  - We relate the energy dissipation processes at the femtosecond (electron-spin
      relaxation time tau el-sp) and nanosecond time scale (Gilbert relaxation
      taualpha) to the microscopic model proposed by Koopmans [Phys. Rev. Lett. 95,
      267207 (2005)]. At both time scales, Elliot-Yafet scattering is proposed as the
      dominant contribution. We controllably manipulate the energy dissipation by
      transition metal doping (Pd) and rare earth doping (Dy) of a Permalloy film.
      While a change in taualpha of more than a factor of 2 is observed, tau el-sp
      remains constant. We explain the discrepancies as due to relaxation channels not
      considered in the model.

PMID- 19113592
TI  - High-pressure effect on PbTiO3: an investigation by Raman and x-ray scattering up
      to 63 GPa.
AB  - We report a room-temperature high-pressure x-ray and Raman scattering
      investigation of lead titanate (PbTiO3) up to 63 GPa. Three continuous phase
      transitions at 13, 20, and 45 GPa between tetragonal-like phases occur. As a
      result, no evidence is found for a pressure-induced morphotropic phase boundary.
      Our study provides experimental evidence that PbTiO3 presents a complex sequence
      of phases accommodating pressure through mechanisms involving oxygen octahedra
      tilting and reentrance of ferroelectricity.

PMID- 19113593
TI  - 1T-TiSe2: semimetal or semiconductor?
AB  - Even though the semimetallic behavior of 1T-TiSe2 seemed to be well established
      by band structure calculations and photoemission results, this conclusion has
      been challenged recently. Two high-resolution photoemission investigations
      deduced semiconducting behavior, however with a very small band gap. Such
      conclusion from photoemission is afflicted, in principle, by the problem of
      determining an unoccupied conduction band by photoemission. This problem is
      solved here by the idea of H2O adsorption onto the van der Waals-like surface,
      causing a distinct bending of the bands and resulting in a filled lowest
      conduction band. The detailed analysis yields undoubtedly semiconducting behavior
      for 1T-TiSe2 and interesting properties of a semiconductor with extremely small
      band gap.

PMID- 19113596
TI  - Coordinated chemomechanical cycles: a mechanism for autonomous molecular motion.
AB  - The second law of thermodynamics requires that directed motion be accompanied by
      dissipation of energy. Here we demonstrate the working principles of a bipedal
      molecular motor. The motor is constructed from DNA and is driven by the
      hybridization of a DNA fuel. We show how the catalytic activities of the feet can
      be coordinated to create a Brownian ratchet that is in principle capable of
      directional and processive movement along a track. This system can be driven away
      from equilibrium, demonstrating the potential of the motor to do work.

PMID- 19113595
TI  - Thermotropic biaxial liquid crystalline phases in a mixture of attractive
      uniaxial rod and disk particles.
AB  - We present the first examples of thermotropic biaxial mesophases in mixtures of
      model attractive uniaxial molecules. Nematic and smectic biaxial phases are
      identified. The nematic biaxial phase has remained a key challenge in the science
      of liquid crystals since it was first proposed almost 40 years ago. Very recently
      the first experimental evidence of stable biaxial nematic phases has been
      obtained in thermotropic liquid crystals of single component biaxial mesogens.
      Still elusive is the possibility of stabilizing biaxial nematic phases in
      mixtures of uniaxial particles. We use Monte Carlo molecular simulations to study
      model mixtures of rodlike and disklike molecules interacting through two
      intermolecular potential models: one incorporating spherically symmetric
      (isotropic) attractive interactions; another with anisotropic attractive
      interactions. These models exhibit nematic and smectic biaxial phases.

PMID- 19113594
TI  - Confinement effect on interparticle potential in nematic colloids.
AB  - We studied the confinement effect on the interaction force in nematic liquid
      crystal colloids with spherical particles inducing planar anchoring. Using
      magneto-optical tweezers, we measured the spatial dependence of the quadrupolar
      structural interparticle force over 4 orders of magnitude. For small separations,
      the interparticle potential follows the power law, whereas for separations larger
      than the sample thickness, it decreases exponentially with the decay length
      proportional to the sample thickness. Experimental results are reproduced by
      using the Landau-de Gennes free-energy minimization approach.

PMID- 19113597
TI  - Fourier transform light scattering of inhomogeneous and dynamic structures.
AB  - Fourier transform light scattering (FTLS) is a novel experimental approach that
      combines optical microscopy, holography, and light scattering for studying
      inhomogeneous and dynamic media. In FTLS the optical phase and amplitude of a
      coherent image field are quantified and propagated numerically to the scattering
      plane. Because it detects all the scattered angles (spatial frequencies)
      simultaneously in each point of the image, FTLS can be regarded as the spatial
      equivalent of Fourier transform infrared spectroscopy, where all the temporal
      frequencies are detected at each moment in time.

PMID- 19113598
TI  - Chiral control of electron transmission through molecules.
AB  - Electron transmission through chiral molecules induced by circularly polarized
      light can be very different for mirror-image structures, a peculiar fact given
      that the electronic energy spectra of the systems are identical. We propose that
      this asymmetry--as large as 10% for resonant transport--arises from different
      dynamical responses of the mirrored structures to coherent excitation. This
      behavior is described in the context of a general novel phenomenon of current
      transfer (transfer of charge with its momentum information) and accounts for the
      observed asymmetry and its dependence on structure.

PMID- 19113599
TI  - Glass transition and aging in dense suspensions of thermosensitive microgel
      particles.
AB  - We report a thermosensitive microgel suspension that can be tuned reversibly
      between the glass state at low temperature and the liquid state at high
      temperature. Unlike hard spheres, we find that the glass transition for these
      suspensions is governed by both the volume fraction and the softness of the
      particles, where softer suspensions form a glass at higher effective volume
      fractions. In the glass state, these suspensions show aging where the relaxation
      times increase linearly with age, irrespective of the degree of particle
      softness. This relaxation scaling is in contrast with hard sphere behavior but
      consistent with the soft glassy rheology model.

PMID- 19113600
TI  - Comment on "restoring the density-gradient expansion for exchange in solids and
      surfaces".

PMID- 19113602
TI  - Measurement of the decay of Fock states in a superconducting quantum circuit.
AB  - We demonstrate the controlled generation of Fock states with up to 15 photons in
      a microwave coplanar waveguide resonator coupled to a superconducting phase
      qubit. The subsequent decay of the Fock states, due to dissipation, is then
      monitored by varying the time delay between preparing the state and performing a
      number-state analysis. We find that the decay dynamics can be described by a
      master equation where the lifetime of the n-photon Fock state scales as 1/n, in
      agreement with theory. We have also generated a coherent state in the microwave
      resonator, and monitored its decay process. We demonstrate that the coherent
      state maintains a Poisson distribution as it decays, with an average photon
      number that decreases with the same characteristic decay time as the one-photon
      Fock state.

PMID- 19113603
TI  - Process tomography of field damping and measurement of Fock state lifetimes by
      quantum nondemolition photon counting in a cavity.
AB  - The relaxation of a quantum field stored in a high-Q superconducting cavity is
      monitored by nonresonant Rydberg atoms. The field, subjected to repetitive
      quantum nondemolition photon counting, undergoes jumps between photon number
      states. We select ensembles of field realizations evolving from a given Fock
      state and reconstruct the subsequent evolution of their photon number
      distributions. We realize in this way a tomography of the photon number
      relaxation process yielding all the jump rates between Fock states. The damping
      rates of the n photon states (0 < or = n < or = 7) are found to increase linearly
      with n. The results are in excellent agreement with theory including a small
      thermal contribution.

PMID- 19113604
TI  - Semiclassical theory of time-reversal focusing.
AB  - Time-reversal mirrors have been successfully implemented for various kinds of
      waves propagating in complex media. In particular, acoustic waves in chaotic
      cavities exhibit a refocalization that is extremely robust against external
      perturbations or the partial use of the available information. We develop a
      semiclassical approach in order to quantitatively describe the refocusing signal
      resulting from an initially localized wave packet. The time-dependent
      reconstructed signal grows linearly with the temporal window of injection, in
      agreement with the acoustic experiments, and reaches the same spatial extension
      of the original wave packet. We explain the crucial role played by the chaotic
      dynamics for the reconstruction of the signal and its stability against external
      perturbations.

PMID- 19113605
TI  - Topological degeneracy and vortex manipulation in Kitaev's honeycomb model.
AB  - The classification of loop symmetries in Kitaev's honeycomb lattice model
      provides a natural framework to study the Abelian topological degeneracy. We
      derive a perturbative low-energy effective Hamiltonian that is valid to all
      orders of the expansion and for all possible toroidal configurations. Using this
      form we demonstrate at what order the system's topological degeneracy is lifted
      by finite size effects and note that in the thermodynamic limit it is robust to
      all orders. Further, we demonstrate that the loop symmetries themselves
      correspond to the creation, propagation, and annihilation of fermions. We note
      that these fermions, made from pairs of vortices, can be moved with no additional
      energy cost.

PMID- 19113606
TI  - Quantum Darwinism in quantum Brownian motion.
AB  - Quantum Darwinism--the redundant encoding of information about a decohering
      system in its environment--was proposed to reconcile the quantum nature of our
      Universe with apparent classicality. We report the first study of the dynamics of
      quantum Darwinism in a realistic model of decoherence, quantum Brownian motion.
      Prepared in a highly squeezed state--a macroscopic superposition--the system
      leaves records whose redundancy increases rapidly with initial delocalization.
      Redundancy appears rapidly (on the decoherence time scale) and persists for a
      long time.

PMID- 19113607
TI  - How accurately does the free complement wave function of a helium atom satisfy
      the Schrodinger equation?
AB  - The local energy defined by Hpsi/psi must be equal to the exact energy E at any
      coordinate of an atom or molecule, as long as the psi under consideration is
      exact. The discrepancy from E of this quantity is a stringent test of the
      accuracy of the calculated wave function. The H-square error for a normalized
      psi, defined by sigma2 identical with psi|(H-E)2|psi, is also a severe test of
      the accuracy. Using these quantities, we have examined the accuracy of our wave
      function of a helium atom calculated using the free complement method that was
      developed to solve the Schrodinger equation. Together with the variational upper
      bound, the lower bound of the exact energy calculated using a modified Temple's
      formula ensured the definitely correct value of the helium fixed-nucleus ground
      state energy to be -2.903,724,377,034,119,598,311,159,245, 194,4 a.u., which is
      correct to 32 digits.

PMID- 19113608
TI  - Asymptotic teleportation scheme as a universal programmable quantum processor.
AB  - We consider a scheme of quantum teleportation where a receiver has multiple (N)
      output ports and obtains the teleported state by merely selecting one of the N
      ports according to the outcome of the sender's measurement. We demonstrate that
      such teleportation is possible by showing an explicit protocol where N pairs of
      maximally entangled qubits are employed. The optimal measurement performed by a
      sender is the square-root measurement, and a perfect teleportation fidelity is
      asymptotically achieved for a large N limit. Such asymptotic teleportation can be
      utilized as a universal programmable processor.

PMID- 19113609
TI  - Invariant quantities in shear flow.
AB  - The dynamics of systems out of thermal equilibrium is usually treated on a case
      by-case basis without knowledge of fundamental and universal principles. We
      address this problem for a class of driven steady states, namely, those
      mechanically driven at the boundaries such as complex fluids under shear. From a
      nonequilibrium counterpart to detailed balance (NCDB) we derive a remarkably
      simple set of invariant quantities which remain unchanged when the system is
      driven. These new nonequilibrium relations are both exact and valid arbitrarily
      far from equilibrium. Furthermore, they enable the systematic calculation of
      transition rates in driven systems with state spaces of arbitrary connectivity.

PMID- 19113610
TI  - Mutual friction in a cold color-flavor-locked superfluid and r-mode instabilities
      in compact stars.
AB  - Dissipative processes acting in rotating neutron stars are essential in
      preventing the growth of the r-mode instability. We estimate the damping time of
      r modes of a hypothetical compact quark star made up by color-flavor-locked quark
      matter at a temperature T < or approximately 0.01 MeV. The dissipation that we
      consider is due to the mutual friction force between the normal and the
      superfluid component arising from the elastic scattering of phonons with
      quantized vortices. This process is the dominant one for temperatures T < or
      approximately 0.01 MeV, where the mean free path of phonons due to their self
      interactions is larger than the radius of the star. We find that r-mode
      oscillations are efficiently damped by this mechanism for pulsars rotating at
      frequencies of the order of 1 Hz at most. Our analysis rules out the possibility
      that cold pulsars rotating at higher frequencies are entirely made up by color
      flavor-locked quark matter.

PMID- 19113611
TI  - Lattice analysis for the energy scale of QCD phenomena.
AB  - We formulate a new framework in lattice QCD to study the relevant energy scale of
      QCD phenomena. By considering the Fourier transformation of link variable, we can
      investigate the intrinsic energy scale of a physical quantity nonperturbatively.
      This framework is broadly available for all lattice QCD calculations. We apply
      this framework for the quark-antiquark potential and meson masses in quenched
      lattice QCD. The gluonic energy scale relevant for the confinement is found to be
      less than 1 GeV in the Landau or Coulomb gauge.

PMID- 19113614
TI  - Dijet signals for low mass strings at the Large Hadron Collider.
AB  - Assuming that the fundamental string mass scale is in the TeV range and the
      theory is weakly coupled, we discuss possible signals of string physics at the
      Large Hadron Collider (LHC). In D-brane constructions, the dominant contributions
      to full-fledged string amplitudes for all the common QCD parton subprocesses
      leading to dijets are completely independent of the details of compactification,
      and can be evaluated in a parameter-free manner. We make use of these amplitudes
      evaluated near the first resonant pole to determine the discovery potential of
      LHC for the first Regge excitations of the quark and gluon. Remarkably, the reach
      of LHC after a few years of running can be as high as 6.8 TeV. Even after the
      first 100 pb(-1) of integrated luminosity, string scales as high as 4.0 TeV can
      be discovered. Data on pp-->directgamma + jet can provide corroboration for
      string physics at scales as high as 5 TeV.

PMID- 19113616
TI  - Coupled-channel evaluations of cross sections for scattering involving particle
      unstable resonances.
AB  - How does the scattering cross section change when the colliding bound-state
      fragments are allowed particle-emitting resonances? This question is explored in
      the framework of a multichannel algebraic scattering method of determining
      nucleon-nucleus cross sections at low energies. Two cases are examined, the first
      being a gedanken investigation in which n + 12C scattering is studied with the
      target states assigned artificial widths. The second is a study of neutron
      scattering from 8Be, a nucleus that is particle unstable. Resonance character of
      the target states markedly varies evaluated cross sections from those obtained
      assuming stability in the target spectrum.

PMID- 19113615
TI  - S parameter and pseudo Nambu-Goldstone boson mass from lattice QCD.
AB  - We present a lattice calculation of L10, one of the low-energy constants in
      chiral perturbation theory, and the charged-neutral pion squared-mass splitting,
      using dynamical overlap fermion. The exact chiral symmetry of the overlap fermion
      allows us to reliably extract these quantities from the difference of the vacuum
      polarization functions for vector and axial-vector currents. In the context of
      the technicolor models, these two quantities are read as the S parameter and the
      pseudo Nambu-Goldstone boson mass, respectively, and play an important role in
      discriminating the models from others. This calculation can serve as a
      feasibility study of the lattice techniques for more general technicolor gauge
      theories.

PMID- 19113617
TI  - Orientation-dependent multiphoton ionization in wide band gap crystals.
AB  - Using different crystalline dielectrics and intense femtosecond laser pulses, we
      show that nonlinear absorption depends on sample orientation. This arises
      primarily because of the direction dependence of the effective mass of the
      electron. The multiphoton nature of the interaction creates a local probe that
      can be used anywhere in the material. We show that the structure of crystal
      quartz is not changed by repeated illumination of the focal region with 45 fs
      pulses.

PMID- 19113618
TI  - Magneto-optical trap for polar molecules.
AB  - We propose a method for laser cooling and trapping a substantial class of polar
      molecules and, in particular, titanium (II) oxide (TiO). This method uses pulsed
      electric fields to nonadiabatically remix the ground-state magnetic sublevels of
      the molecule, allowing one to build a magneto-optical trap based on a
      quasicycling J' = J'' -1 transition. Monte Carlo simulations of this
      electrostatically remixed magneto-optical trap demonstrate the feasibility of
      cooling TiO to a temperature of 10 micrpK and trapping it with a radiation
      pumping-limited lifetime on the order of 80 ms.

PMID- 19113619
TI  - Observation of a push force on the end face of a nanometer silica filament
      exerted by outgoing light.
AB  - There are two different proposals for the momentum of light in a transparent
      dielectric of refractive index n: Minkowski's version nE/c and Abraham's version
      E/(nc), where E and c are the energy and vacuum speed of light, respectively.
      Despite many tests and debates over nearly a century, momentum of light in a
      transparent dielectric remains controversial. In this Letter, we report a direct
      observation of the inward push force on the free end face of a nanometer silica
      filament exerted by the outgoing light. Our results suggest that Abraham's
      momentum is correct.

PMID- 19113620
TI  - Octave-spanning Raman comb with carrier envelope offset control.
AB  - We report that adiabatic manipulation of a Raman process allows us to produce an
      optical-frequency comb from single-frequency lasers. We realize an octave
      spanning Raman comb with carrier-envelope-offset frequency control, by using dual
      frequency laser radiation locked on a single laser cavity and simultaneously its
      second harmonic. It is shown that in both the temporal and spectral domains,
      locking the dual frequencies on a single laser cavity provides control of the
      carrier-envelope-offset frequency at integer multiples of the free spectral range
      of the laser cavity.

PMID- 19113622
TI  - Chaotic communication via temporal transfer entropy.
AB  - We propose a new perspective on communication using chaos. A binary message is
      encoded into the temporally causal relations on a coupled maps ring of N chaotic
      nodes. From the analysis of temporal transfer entropy, the masked information can
      be recovered from transmitted signals at the receiver. The communication scheme
      has been demonstrated to be robust against external noise and some traditional
      attacks.

PMID- 19113621
TI  - Analytical approach to initiation of propagating fronts.
AB  - We consider the problem of initiation of a propagating wave in a one-dimensional
      bistable or excitable fiber. In the Zeldovich-Frank-Kamenetskii equation, also
      known as the Nagumo equation and Schlogl model, the key role is played by the
      "critical nucleus" solution whose stable manifold is the threshold surface
      separating initial conditions leading to the initiation of propagation and decay.
      An approximation of this manifold by its tangent linear space yields an
      analytical criterion of initiation which is in good agreement with direct
      numerical simulations.

PMID- 19113623
TI  - Large-scale intermittency of liquid-metal channel flow in a magnetic field.
AB  - We predict a novel flow regime in liquid metals under the influence of a magnetic
      field. It is characterized by long periods of nearly steady, two-dimensional flow
      interrupted by violent three-dimensional bursts. Our prediction has been obtained
      from direct numerical simulations in a channel geometry at low magnetic Reynolds
      number and translates into physical parameters which are amenable to experimental
      verification under laboratory conditions. The new regime occurs in a wide range
      of parameters and may have implications for metallurgical applications.

PMID- 19113624
TI  - Wave turbulence on the surface of a ferrofluid in a magnetic field.
AB  - We report the observation of wave turbulence on the surface of a ferrofluid
      mechanically forced and submitted to a static normal magnetic field. We show that
      magnetic surface waves arise only above a critical field. The power spectrum of
      their amplitudes displays a frequency-power law leading to the observation of a
      magnetic wave turbulence regime which is experimentally shown to involve a 4-wave
      interaction process. The existence of the regimes of gravity, magnetic and
      capillary wave turbulence is reported in the phase space parameters as well as a
      triple point of coexistence of these three regimes. Most of these features are
      understood using dimensional analysis or the dispersion relation of the
      ferrohydrodynamic surface waves.

PMID- 19113625
TI  - Transverse instability of bubbles in viscoelastic channel flows.
AB  - The trajectory of a stream of bubbles is measured in a microfluidic pressure
      driven flow. For Newtonian fluids with or without surfactants, or viscoelastic
      fluids without surfactants, the bubbles maintain stable positions equally spaced
      along the channel center line. However, for viscoelastic fluids with surfactant,
      a transverse instability is observed, which has the characteristics of a linear
      instability, whose growth rate increases with the speed of the flow. The results
      are shown to be consistent with the action of shear-induced normal stresses in
      the fluid, where the magnitude increases with shear rate and so is augmented by
      surfactants that make the interface rigid.

PMID- 19113612
TI  - Measurement of Bs0 mixing parameters from the flavor-tagged decay Bs0-->J/psiphi.
AB  - From an analysis of the flavor-tagged decay Bs0-->J/psiphi we obtain the width
      difference between the Bs0 light and heavy mass eigenstates, DeltaGammas = 0.19+/
      0.07(stat)(-0.01)+0.02(syst) ps(-1), and the CP-violating phase, phi s= -0.57(
      0.30)+0.24(stat)(-0.02)+0.08(syst). The allowed 90% CL intervals of DeltaGammas
      and phi s are 0.06 < DeltaGammas < 0.30 ps(-1) and -1.20 < phi s < 0.06,
      respectively. The data sample corresponds to an integrated luminosity of 2.8 fb(
      1) accumulated with the D0 detector at the Fermilab Tevatron collider.

PMID- 19113626
TI  - Nonlocal interface dynamics and pattern formation in gravity-driven unsaturated
      flow through porous media.
AB  - Existing continuum models of multiphase flow in porous media are unable to
      explain why preferential flow (fingering) occurs during infiltration into
      homogeneous, dry soil. Following a phase-field methodology, we propose a
      continuum model that accounts for an apparent surface tension at the wetting
      front and does not introduce new independent parameters. The model reproduces the
      observed features of fingered flows, in particular, the higher saturation of
      water at the tip of the fingers, which is believed to be essential for the
      formation of fingers. From a linear stability analysis, we predict that finger
      velocity and finger width both increase with infiltration rate, and the
      predictions are in quantitative agreement with experiments.

PMID- 19113627
TI  - Alfven instability in a compressible flow.
AB  - A new ideal magnetohydrodynamic instability is presented. It is shown that linear
      incompressible Alfvenic disturbances can get over-reflected and exponentially
      amplified in compressible plasma flows. A simple and transparent stability
      criterion for a two-layer model is derived. The instability does not require a
      shear in the flow and may arise for rather moderate sub-Alfvenic flow speeds. It
      is therefore important to be aware of the Alfven instability when dealing with
      laboratory or astrophysical plasma flows.

PMID- 19113629
TI  - Quantum phases of a two-dimensional dipolar fermi gas.
AB  - We examine the superfluid and collapse instabilities of a quasi-two-dimensional
      gas of dipolar fermions aligned by an orientable external field. It is shown that
      the interplay between the anisotropy of the dipole-dipole interaction, the
      geometry of the system, and the p-wave symmetry of the superfluid order parameter
      means that the effective interaction for pairing can be made very large without
      the system collapsing. This leads to a broad region in the phase diagram where
      the system forms a stable superfluid. Analyzing the superfluid transition at
      finite temperatures, we calculate the Berezinskii-Kosterlitz-Thouless temperature
      as a function of the dipole angle.

PMID- 19113628
TI  - Effects of the g factor in semiclassical kinetic plasma theory.
AB  - A kinetic theory for spin plasmas is put forward, generalizing those of previous
      authors. In the model, the ordinary phase space is extended to include the spin
      degrees of freedom. Together with Maxwell's equations, the system is shown to be
      energy conserving. Analyzing the linear properties, it is found that new types of
      wave-particle resonances are possible that depend directly on the anomalous
      magnetic moment of the electron. As a result, new wave modes, not present in the
      absence of spin, appear. The implications of our results are discussed.

PMID- 19113613
TI  - Search for third generation scalar leptoquarks decaying into taub.
AB  - We have searched for third generation leptoquarks (LQ3) using 1.05 fb(-1) of data
      collected with the D0 detector at the Fermilab Tevatron Collider operating at
      sqrt[s]=1.96 TeV. We set a 95% C.L. lower limit of 210 GeV on the mass of a
      scalar LQ3 state decaying solely to a b quark and a tau lepton.

PMID- 19113630
TI  - Avoided-level-crossing spectroscopy with dressed matter waves.
AB  - We devise a method for probing resonances of macroscopic matter waves in shaken
      optical lattices by monitoring their response to slow parameter changes, and show
      that such resonances can be disabled by particular choices of the driving
      amplitude. The theoretical analysis of this scheme reveals far-reaching analogies
      between dressed atoms and time periodically forced matter waves.

PMID- 19113631
TI  - Edge-stress-induced warping of graphene sheets and nanoribbons.
AB  - We show that edge stresses introduce intrinsic ripples in freestanding graphene
      sheets even in the absence of any thermal effects. Compressive edge stresses
      along zigzag and armchair edges of the sheet cause out-of-plane warping to attain
      several degenerate mode shapes. Based on elastic plate theory, we identify
      scaling laws for the amplitude and penetration depth of edge ripples as a
      function of wavelength. We also demonstrate that edge stresses can lead to
      twisting and scrolling of nanoribbons as seen in experiments. Our results
      underscore the importance of accounting for edge stresses in thermal theories and
      electronic structure calculations for freestanding graphene sheets.

PMID- 19113632
TI  - Effective temperatures and activated dynamics for a two-dimensional air-driven
      granular system on two approaches to jamming.
AB  - We present experiments on several distinct effective temperatures in a granular
      system at a sequence of increasing packing densities and at a sequence of
      decreasing driving rates. This includes single-grain measurements based on the
      mechanical energies of both the grains and an embedded oscillator, as well as a
      collective measurement based on the Einstein relation between diffusivity and
      mobility, which all probe different time scales. Remarkably, all effective
      temperatures agree. Furthermore, mobility data along the two trajectories
      collapse when plotted vs effective temperature and exhibit an Arrhenius form with
      the same energy barrier as the microscopic relaxation time.

PMID- 19113633
TI  - Dynamics of spin and orbital phase transitions in YVO3.
AB  - YVO3 exhibits a well separated sequence of orbital and spin order transitions at
      200 and 116 K, followed by a combined spin-orbital reorientation at 77 K. It is
      shown that the spin order can be destroyed by a sufficiently strong optical pulse
      within less than 4 ps. In contrast, the orbital reordering transition from C-type
      to G-type orbital order is slower than 100 ps and goes via an intermediate
      nonthermal phase. We propose that the dynamics of phase transitions is subjected
      to symmetry relations between the associated phases.

PMID- 19113634
TI  - Critical behavior of symmetrical fluid mixtures in random pores.
AB  - We study the liquid-liquid demixing of a binary mixture with a symmetrical
      coupling to the quenched disorder by means of computer simulation. The critical
      point in the thermodynamic limit is estimated both by assuming the knowledge of
      the critical exponents and independently of them. The finite-size scaling
      analysis of the susceptibilities and the values of the critical amplitudes show
      that the universality class of the fluid mixture is compatible with the diluted
      quenched-Ising model. Our findings extend the class of systems exhibiting the
      same critical behavior of diluted antiferromagnets.

PMID- 19113635
TI  - Multiple bifurcation types and the linear dynamics of ion sputtered surfaces.
AB  - We study the patterns formed on ion sputtered Si surfaces as a function of ion
      energy and incidence angle, and identify a region in parameter space where the
      flat surface is stable. The boundaries between the stable and pattern-forming
      regions represent mathematical bifurcations. Our data set exhibits at least two
      different bifurcation types. We discuss the constraints imposed by these
      observations on the correct model of long wavelength dynamics of ion sputtered
      surfaces.

PMID- 19113636
TI  - Weighing supported nanoparticles: size-selected clusters as mass standards in
      nanometrology.
AB  - We present a new approach to quantify the mass and 3D shape of nanoparticles on
      supports, using size-selected nanoclusters as mass standards in scanning
      transmission electron microscope. Through quantitative image intensity analysis,
      we show that the integrated high angle annular dark field intensities of size
      selected gold clusters soft-landed on graphite display a monotonic dependence on
      the cluster size as far as approximately 6500 atoms. We applied this mass
      standard to study gold nanoparticles prepared by thermal vapor deposition and by
      colloidal wet chemistry, and from which we deduced the shapes of these two types
      of nanoparticles as expected.

PMID- 19113637
TI  - Entanglement effects in capillary waves on liquid polymer films.
AB  - Overdamped surface capillary wave relaxations on molten polymer films were
      measured using x-ray photon correlation spectroscopy. We found a transition from
      a single through a stretched to another single exponential regime as the
      temperature is decreased from well above to near the bulk glass transition
      temperature. A universal scaling of the dynamics was discovered over a wide range
      of film thicknesses, temperatures, and molecular weights (except in the multiple
      relaxation regime). These observations are justified by hydrodynamic theory and
      the time-temperature superposition principle by considering an effective
      viscosity instead of the bulk zero shear viscosity.

PMID- 19113638
TI  - Friction at atomic-scale surface steps: experiment and theory.
AB  - Experiments performed by friction force microscopy at atomic-scale surface steps
      on graphite, MoS2, and NaCl in ambient conditions are presented. Both step-down
      and step-up scans exhibit higher frictional forces at the edge, but distinguish
      in their load dependence: While the additional frictional force due to the step
      edge increases linearly with load if the tip has to jump a step up, it remains
      constant for downward jumps. This phenomenon represents a universal effect that
      can be explained in terms of a modified Prandtl-Tomlinson model featuring a
      Schwoebel-Ehrlich barrier at steps.

PMID- 19113639
TI  - Terahertz coherent control of optically dark paraexcitons in Cu2O.
AB  - Intense multiterahertz fields of order megavolts per centimeter are used to
      coherently promote optically dark and dense paraexcitons in Cu2O from the 1s into
      the 2p state. The nonlinear field response of the intraexcitonic degrees of
      freedom is directly monitored in the time domain via ultrabroadband electro-optic
      sampling. The experimental results are analyzed with a microscopic many-body
      theory, identifying up to two internal Rabi cycles. The effects of population
      inversion and ponderomotive contributions are disentangled.

PMID- 19113640
TI  - Single-particle and collective mode couplings associated with 1- and 2
      directional electronic ordering in metallic RTe3 (R=Ho,Dy,Tb).
AB  - The coupling of phonons with collective modes and single-particle gap excitations
      associated with one- (1d) and two-directional (2d) electronically driven charge
      density wave (CDW) ordering in metallic RTe3 is investigated as a function of
      rare-earth ion chemical pressure (R=Tb,Dy,Ho) using femtosecond pump-probe
      spectroscopy. From the T dependence of the CDW gap DeltaCDW and the amplitude
      mode, we find that while the transition to a 1d-CDW ordered state at Tc1
      initially proceeds in an exemplary mean-field-like fashion, below Tc1, DeltaCDW
      is depressed and departs from the mean-field behavior. The effect is apparently
      triggered by resonant mode mixing of the amplitude mode with a totally symmetric
      phonon at 1.75 THz. At low temperatures, when the state evolves into a 2d-CDW
      ordered state at Tc2 in the DyTe3 and HoTe3, additional much weaker mode mixing
      is evident but no soft mode is observed.

PMID- 19113641
TI  - Gruneisen ratio at the kondo-breakdown quantum critical point.
AB  - We show that the scenario of a multiscale Kondo-breakdown quantum critical point
      gives rise to a divergent Gruneisen ratio with an anomalous exponent 0.7. In
      particular, we fit the experimental data of YbRh2(Si0.95Ge0.05)2 for a specific
      heat, thermal expansion, and Gruneisen ratio based on our simple analytic
      expressions. A reasonable agreement between the experiment and theory is found
      for the temperature range between 0.4 and 10 K. We discuss how the Gruneisen
      ratio is a key measurement to discriminate between the Kondo-breakdown and spin
      density wave theories.

PMID- 19113642
TI  - Vortices, zero modes, and fractionalization in the bilayer-graphene exciton
      condensate.
AB  - A real-space formulation is given for the recently discussed exciton condensate
      in a symmetrically biased graphene bilayer. We show that in the continuum limit
      an oddly quantized vortex in this condensate binds exactly one zero-mode per
      valley index of the bilayer. In the full lattice model, the zero modes are split
      slightly due to intervalley mixing. We support these results by an exact
      numerical diagonalization of the lattice Hamiltonian. We also discuss the effect
      of the zero modes on the charge content of these vortices and deduce some of
      their interesting properties.

PMID- 19113643
TI  - Anomalous coulomb drag in electron-hole bilayers.
AB  - We report Coulomb drag measurements on GaAs-AlGaAs electron-hole bilayers. The
      two layers are separated by a 10 or 25 nm barrier. Below T approximately 1 K we
      find two features that a Fermi-liquid picture cannot explain. First, the drag on
      the hole layer shows an upturn, which may be followed by a downturn. Second, the
      effect is either absent or much weaker in the electron layer, even though the
      measurements are within the linear response regime. Correlated phases have been
      anticipated in these, but surprisingly, the experimental results appear to
      contradict Onsager's reciprocity theorem.

PMID- 19113644
TI  - Twist instability in strongly correlated carbon nanotubes.
AB  - We show that strong Luttinger correlations of the electron liquid in armchair
      carbon nanotubes significantly enhance the onset temperature of the putative
      twist Peierls instability and lead to its 1/R3 dependence on the tube radius.
      Depending on the values of the coupling constants the umklapp processes can
      either assist or compete with the twist instability. In the case of a competition
      the umklapp processes win in wide tubes. In narrow tubes the outcome of the
      competition depends on the relative strength of the e-e and e-ph backscattering.
      Our estimates show that the twist instability may be realized in freestanding
      (5,5) tubes.

PMID- 19113645
TI  - Edge states and optical transition energies in carbon nanoribbons.
AB  - The edge states and optical transition energies in carbon nanoribbons are
      investigated with density-functional calculations. While the ground state of
      zigzag ribbons is spin polarized, defects at the edges destroy spin polarization
      and lead to a nonmagnetic ground state. Scanning tunneling spectroscopy will thus
      show different features depending on edge quality. Optical transition energies in
      nanoribbons Eii are strongly affected by the edges and confinement, which
      introduce a term inversely proportional to their width. After removing that term,
      the scaling of Eii is quantitatively similar to that in carbon nanotubes.

PMID- 19113646
TI  - Charge transport and tunneling in single-walled carbon nanotube bundles.
AB  - We investigate experimentally the transport properties of single-walled carbon
      nanotube bundles as a function of temperature and applied current over broad
      intervals of these variables. The analysis is performed on arrays of nanotube
      bundles whose axes are aligned along the direction of the externally supplied
      bias current. The data are found consistent with a charge transport model
      governed by the tunneling between metallic regions occurring through potential
      barriers generated by a nanotube's contact areas or bundle surfaces. Based on
      this model and on experimental data, we describe quantitatively the dependencies
      of the height of these barriers upon bias current and temperature.

PMID- 19113647
TI  - Kondo effect in carbon nanotube quantum dots with spin-orbit coupling.
AB  - Motivated by recent experimental observation of spin-orbit coupling in carbon
      nanotube quantum dots [F. Kuemmeth, Nature (London) 452, 448 (2008)], we
      investigate in detail its influence on the Kondo effect. The spin-orbit coupling
      intrinsically lifts out the fourfold degeneracy of a single electron in the dot,
      thereby breaking the SU(4) symmetry and splitting the Kondo resonance even at
      zero magnetic field. When the field is applied, the Kondo resonance further
      splits and exhibits fine multipeak structures resulting from the interplay of
      spin-orbit coupling and the Zeeman effect. A microscopic cotunneling process for
      each peak can be uniquely identified. Finally, a purely orbital Kondo effect in
      the two-electron regime is also predicted.

PMID- 19113648
TI  - Properties of non-Abelian fractional quantum Hall states at filling nu = k/r.
AB  - We compute the physical properties of non-Abelian fractional quantum Hall (FQH)
      states described by Jack polynomials at general filling nu = k/r. For r = 2,
      these states are the Zk Read-Rezayi parafermions, whereas for r > 2 they
      represent new FQH states. The r = k+1 states, multiplied by a Vandermonde
      determinant, are a non-Abelian alternative construction of states at fermionic
      filling 2/5,3/7,4/9,.... We obtain the thermal Hall coefficient, the quantum
      dimensions, the electron scaling exponent, and the non-Abelian quasihole
      propagator. The properties of the r > 2 Jack polynomials indicate they are
      correlators of fields of nonunitary conformal field theories (CFT), but the CFT
      FQH connection fails when invoked to compute physical properties such as the
      quasihole propagator. The quasihole wave function, written as a coherent state
      representation of Jack polynomials, has an identical structure for all non
      Abelian states.

PMID- 19113649
TI  - Finite size effects on helical edge states in a quantum spin-Hall system.
AB  - The hallmark of the spin-Hall insulator is the presence of gapless edge states of
      different spins moving in opposite directions. Through analytical solutions in a
      model calculation for a strip of finite width, we find that edge states on the
      two sides can couple together to produce a gap in the spectrum, destroying the
      quantum spin-Hall effect. The application of a magnetic field can however modify
      and even remove the gap by shifting the momenta of the edge states relative to
      each other.

PMID- 19113650
TI  - Electronic structure of the NaxCoO2 surface.
AB  - The idea that surface effects may play an important role in suppressing eg' Fermi
      surface pockets on NaxCoO2 (0.333 < or = x < or = 0.75) has been frequently
      proposed to explain the discrepancy between local-density approximation
      calculations which find eg' hole pockets present and Angle resolved photoemission
      spectra (ARPES) experiments, which do not observe the hole pockets. Since ARPES
      is a surface sensitive technique, it is important to investigate the effects that
      surface formation will have on the electronic structure. We show that a
      combination of surface formation and contamination effects could resolve the
      ongoing controversy between ARPES experiments and theory.

PMID- 19113651
TI  - Fractional quantum Hall state in coupled cavities.
AB  - We propose a scheme to realize the fractional quantum Hall system with atoms
      confined in a two-dimensional array of coupled cavities. Our scheme is based on
      simple optical manipulation of atomic internal states and intercavity hopping of
      virtually excited photons. It is shown that, as well as the fractional quantum
      Hall system, any system of hard-core bosons on a lattice in the presence of an
      arbitrary Abelian vector potential can be simulated solely by controlling the
      phases of constantly applied lasers. The scheme, for the first time, exploits the
      core advantage of coupled cavity simulations, namely, the individual
      addressability of the components, and also brings the gauge potential into such
      simulations as well as the simple optical creation of particles.

PMID- 19113652
TI  - Realizing and detecting the quantum Hall effect without landau levels by using
      ultracold atoms.
AB  - We design an ingenious scheme to realize Haldane's quantum Hall model without
      Landau levels by using ultracold atoms trapped in an optical lattice. Three
      standing-wave laser beams are used to construct a wanted honeycomb lattice, where
      different on site energies in two sublattices required in the model can be
      implemented through tuning the phase of one laser beam. The staggered magnetic
      field is generated from the light-induced Berry phase. Moreover, we establish a
      relation between the Hall conductivity and the atomic density, enabling us to
      detect the Chern number with the typical density-profile-measurement technique.

PMID- 19113653
TI  - Microwave photoresistance in dc-driven 2D systems at cyclotron resonance
      subharmonics.
AB  - We study microwave photoresistivity oscillations in a high-mobility two
      dimensional electron system subject to strong dc electric fields. We find that
      near the second subharmonic of the cyclotron resonance the frequency of the
      resistivity oscillations with a dc electric field is twice the frequency of the
      oscillations at the cyclotron resonance, its harmonics, or in the absence of
      microwave radiation. This observation is discussed in terms of the microwave
      induced sidebands in the density of states and the interplay between different
      scattering processes in the separated Landau level regime.

PMID- 19113654
TI  - Semifluxon molecule under control.
AB  - Josephson junctions with a phase drop of pi in the ground state allow us to
      create vortices of supercurrent carrying only half of the magnetic flux quantum
      Phi0 approximately 2.07 x 10(-15) Wb. Such semifluxons have twofold degenerate
      ground states denoted upward arrow (with flux +Phi0/2 and supercurrent
      circulating clockwise) and downward arrow (with flux -Phi0/2 and supercurrent
      circulating counterclockwise). We investigate a molecule consisting of two
      coupled semifluxons in a 0-pi-0 long Josephson junction. The fluxes (polarities)
      of semifluxons are measured by two on-chip SQUIDs. By varying the dc bias current
      applied to the 0-pi-0 junction, we demonstrate controllable manipulation and
      switching between two states, upward arrow downward arrow and downward arrow
      upward arrow, of a semifluxon molecule. These results provide a major step
      towards employing semifluxons as bits or qubits for classical and quantum digital
      electronics.

PMID- 19113655
TI  - Quasiparticle poisoning and Josephson current fluctuations induced by Kondo
      impurities.
AB  - We introduce a toy model that allows us to study the physical properties of a
      spin impurity coupled to the electrons in the superconducting island. We show
      that, when the coupling of the spin is of the order of the superconducting gap
      Delta, two almost degenerate subgap states are formed. By computing the Berry
      phase that is associated with the superconducting phase rotations in this model,
      we prove that these subgap states are characterized by a different charge and
      demonstrate that the switching between these states has the same effect as
      quasiparticle poisoning (unpoisoning) of the island. We also show that an
      impurity coupled to both the island and the lead generates Josepshon current
      fluctuations.

PMID- 19113656
TI  - Origin of the spatial variation of the pairing gap in bi-based high temperature
      cuprate superconductors.
AB  - Recently, scanning tunneling microscopy on the Bi-2212 cuprate superconductor has
      revealed a spatial variation of the energy gap that is directly correlated with a
      modulation of the apical oxygen position. We identify two mechanisms by which out
      of-plane oxygens can modulate the pairing interaction within the CuO2 layer: a
      covalency between the x2-y2 band and apical p orbital, and a screening of
      correlation U by apical oxygen polarization. Both effects strongly depend on the
      apical oxygen position, and their cooperative action explains the experiment.

PMID- 19113657
TI  - Electron-phonon interactions in superconducting La1.84Sr0.16CuO4 films.
AB  - We have measured quasiparticle tunneling across a junction perpendicular to the
      superconducting copper oxide planes. The tunneling spectra show peaks in the
      density of states. There are 11 minima in the second derivative d2I/dV2, where I
      is the current and V the voltage, suggesting multiple boson-quasiparticle
      interactions. These minima match precisely with the published Raman scattering
      data, leading us to conclude that the relevant bosons in superconducting
      La1.84Sr0.16CuO4 films are phonons.

PMID- 19113658
TI  - Single domain magnetic helicity and triangular chirality in structurally
      enantiopure Ba3NbFe3Si2O14.
AB  - A novel doubly chiral magnetic order is found in the structurally chiral
      langasite compound Ba3NbFe3Si2O14. The magnetic moments are distributed over
      planar frustrated triangular lattices of triangle units. On each of these they
      form the same triangular configuration. This ferrochiral arrangement is helically
      modulated from plane to plane. Unpolarized neutron scattering on a single crystal
      associated with spherical neutron polarimetry proved that a single triangular
      chirality together with a single helicity is stabilized in an enantiopure
      crystal. A mean-field analysis allows us to discern the relevance on this
      selection of a twist in the plane to plane super-superexchange paths.

PMID- 19113659
TI  - Thermodynamics of the spin Luttinger liquid in a model ladder material.
AB  - The phase diagram in temperature and magnetic field of the metal-organic, two
      leg, spin-ladder compound (C5H12N)2CuBr4 is studied by measurements of the
      specific heat and the magnetocaloric effect. We demonstrate the presence of an
      extended spin Luttinger-liquid phase between two field-induced quantum critical
      points and over a broad range of temperature. Based on an ideal spin-ladder
      Hamiltonian, comprehensive numerical modeling of the ladder specific heat yields
      excellent quantitative agreement with the experimental data across the entire
      phase diagram.

PMID- 19113660
TI  - Dynamic origin of azimuthal modes splitting in vortex-state magnetic dots.
AB  - A spin-wave theory explaining experimentally observed frequency splitting of
      dynamical spin excitations with azimuthal symmetry of a magnetic dot in a vortex
      ground state is developed. It is shown that this splitting is a result of the
      dipolar hybridization of three spin-wave modes of a dot having azimuthal indices
      |m|=1: two high-frequency azimuthal dipolar modes of the in-plane part of the
      vortex with indices m = +/-1 and a low-frequency (Goldstone-like) gyrotropic
      mode, describing translational motion of the vortex core and having index m = +1.
      The analytically calculated magnitude of the frequency splitting is proportional
      to the ratio of the dot thickness to its radius and quantitatively agrees with
      the results of time-resolved Kerr experiments.

PMID- 19113661
TI  - Magnetic "dead" layer at a complex oxide interface.
AB  - Recent magnetic measurements at La0.67Ca0.33MnO3/YBa2Cu3O7 interfaces led to
      conflicting interpretations: a magnetic "dead" layer on the LCMO side or
      antiparallel Cu and Mn magnetic moments. Here we report results of first
      principles density-functional calculations of position-dependent magnetic
      couplings between interlayer and intralayer Mn atoms. The couplings in the first
      few layers near the interface are found to be weak ferromagnetic or even
      antiferromagnetic. The results suggest that a "dead" magnetic layer 2-3 atoms
      thick is present, as needed to account for the observations.

PMID- 19113662
TI  - Coresonant enhancement of spin-torque critical currents in spin valves with a
      synthetic-ferrimagnet free layer.
AB  - It is experimentally shown that the critical current for onset of spin torque
      instability in current-perpendicular-to-plane spin valves can be strongly
      increased using "synthetic-ferrimagnet" free layers of form FM1/Ru/FM2
      (FM=ferrromagnet). However, this increase occurs for only one polarity of bias
      current. A two-macrospin model is shown to reproduce the observations. The model
      suggests that this phenomenon is related to a polarity-dependent, spin torque
      induced coresonance between the two natural dynamic modes of the FM1/FM2 couple.
      The coresonance condition facilitates energy transfer out of the spin-torque
      destabilized mode into the other stable mode whose effective damping (or line
      width) is strongly enhanced by spin torques.

PMID- 19113663
TI  - Magnetic exchange interaction between rare-earth and Mn ions in multiferroic
      hexagonal manganites.
AB  - We report a study of magnetic dynamics in multiferroic hexagonal manganite HoMnO3
      by far-infrared spectroscopy. The low-temperature magnetic excitation spectrum of
      HoMnO3 consists of magnetic-dipole transitions of Ho ions within the crystal
      field split J = 8 manifold and of the triangular antiferromagnetic resonance of
      Mn ions. We determine the effective spin Hamiltonian for the Ho ion ground state.
      The magnetic-field splitting of the Mn antiferromagnetic resonance allows us to
      measure the magnetic exchange coupling between the rare-earth and Mn ions.

PMID- 19113664
TI  - Direct evidence for multiferroic magnetoelectric coupling in 0.9BiFeO3-0.1BaTiO3.
AB  - Magnetic, dielectric and calorimetric studies on 0.9BiFeO3-0.1BaTiO3 indicate
      strong magnetoelectric coupling. XRD studies reveal a very remarkable change in
      the rhombohedral distortion angle and a significant shift in the atomic positions
      at the magnetic Tc due to an isostructural phase transition. The calculated
      polarization using Rietveld refined atomic positions scales linearly with
      magnetization. Our results provide the first unambiguous, atomic level evidence
      for magnetoelectric coupling of intrinsic multiferroic origin in a BiFeO3-based
      system.

PMID- 19113665
TI  - Spin-state polarons in lightly-hole-doped LaCoO3.
AB  - Inelastic neutron scattering (INS), electron spin resonance (ESR), and nuclear
      magnetic resonance (NMR) measurements were employed to establish the origin of
      the strong magnetic signal in lightly-hole-doped La1-xSrxCoO3, x approximately
      0.002. Both INS and ESR low temperature spectra show intense excitations with
      large effective g factors approximately 10-18. NMR data indicate the creation of
      extended magnetic clusters. From the Q dependence of the INS magnetic intensity,
      we conclude that the observed anomalies are caused by the formation of
      octahedrally shaped spin-state polarons comprising seven Co ions. The present
      INS, ESR, and NMR data give evidence for two regimes in the lightly-hole-doped
      samples: (i) T<35 K dominated by spin polarons; (ii) T>35 K dominated by
      thermally activated magnetic Co3+ ions.

PMID- 19113666
TI  - Measurement of Cu(II) copper defect dipoles in ferroelectric PbTiO3 using
      electron-nuclear double resonance.
AB  - Point defects associated with Cu(II) in ferroelectric PbTiO3 were determined
      using pulsed electron-nuclear double resonance (ENDOR). Three centers were
      observed, and neighbor 207Pb superhyperfine tensors to the third shell of
      equivalent Pb ions measured. The ENDOR angular dependence showed that Cu(II) is
      incorporated as an acceptor at the Ti site. One center also showed ENDOR from an
      axial fluorine ion. The three defects were determined to be the Cu(II)-oxygen
      vacancy defect dipole, Cu(II) with a complete oxygen octahedron, and a Cu(II)-F-
      defect dipole center.

PMID- 19113667
TI  - Classical Mobius-ring resonators exhibit fermion-boson rotational symmetry.
AB  - The behavior of coupled harmonic oscillators in systems with specified boundary
      conditions is typically characterized by resonances whose frequency spectra
      represent harmonics according to properties of the individual oscillators, the
      interactions between them, and the overall symmetry of the system. Here it is
      demonstrated that classical one- and two-dimensional radio frequency resonators
      constrained to a Mobius topology are the formal partners of cylindrical ring
      resonators, and specifically give rise to half-integral harmonic excitations that
      are orthogonal to the integral excitations of a ring. In particular, the half
      integral harmonics are formally invariant under rotations at a minimum of 4pi
      rather than 2pi rad, in analogy to the rotational symmetry of fermions in quantum
      mechanics. The results offer a pathway for discovery in other physical systems as
      well as the design of novel materials and electronic instrumentation.

PMID- 19113668
TI  - Magnetic-field induced isotropic to nematic liquid crystal phase transition.
AB  - We report on measurements of magnetic-field induced nematic order in the bent
      core liquid crystal 4-chlororesorcinol bis[4-(4-n-dodecyloxybenzoyloxy)
      benzoate]. Using the 31 T solenoid at the National High Magnetic Field
      Laboratory, we have observed, at temperatures less than 1 degrees above the
      clearing point, a first-order transition to the nematic phase. The critical
      magnetic field at which this occurs increases with temperature. We discuss these
      results within the context of both Maier-Saupe and Landau-de Gennes mean-field
      models for the nematic-isotropic transition. The implications of possible
      tetrahedratic order are also discussed. To our knowledge, this is the first
      observation of such a magnetic-field induced transition in a thermotropic liquid
      crystal; the reasons for which this behavior is now attainable are discussed.

PMID- 19113669
TI  - Electrically induced tilt in achiral bent-core liquid crystals.
AB  - We report an electric-field-induced SmA-SmC transition in a liquid crystal formed
      by achiral bent molecules. The steric moment of such molecules is too small to
      spontaneously induce the phases characteristic to the bent-core mesogens. On the
      other hand, its contribution to the thermodynamical properties of the mesophases
      make it possible to induce tilt and polar order by the action of the external
      electric field. This effect is unique for bent mesogens and its physical nature
      differs from an electroclinic effect observed in the SmA* phase of chiral liquid
      crystals.

PMID- 19113670
TI  - Transition from rolling to jamming in thin granular layers.
AB  - We study the granular jamming transition for sheared layers of spherical beads
      ranging in thickness from 1 to 3 times the grain diameter d. As the layer
      thickness increases slightly above d, the measured friction jumps discontinuously
      from 0.02 to >0.1, marking the transition from rolling to jamming. Above a
      critical layer thickness for jamming, the effective granular pressure displays a
      power law increase with thickness. For thin layers, friction and P increases as
      the packing fraction decreases near the jamming transition, in contrast to
      expectations for bulk granular matter.

PMID- 19113671
TI  - Rheology of confined granular flows: scale invariance, glass transition, and
      friction weakening.
AB  - We study fully developed, steady granular flows confined between parallel flat
      frictional sidewalls using numerical simulations and experiments. Above a
      critical rate, sidewall friction stabilizes the underlying heap at an inclination
      larger than the angle of repose. The shear rate is constant and independent of
      inclination over much of the flowing layer. In the direction normal to the free
      surface, the solid volume fraction increases on a scale equal to half the flowing
      layer depth. Beneath a critical depth at which internal friction is invariant,
      grains exhibit creeping and intermittent cage motion similar to that in glasses,
      causing gradual weakening of friction at the walls.

PMID- 19113672
TI  - Elasticity of cisplatin-bound DNA reveals the degree of cisplatin binding.
AB  - Cisplatin was incidentally discovered to suppress cell division and became one of
      the most successful antitumor drugs. It is therapeutically active upon binding to
      DNA and locally kinking it. We demonstrate that after a bimodal modeling, the
      degree of platination of a single DNA molecule can be consistently and reliably
      estimated from elasticity measurements performed with magnetic tweezers. We
      predicted and measured for the first time two separate persistence lengths of
      kinked DNA at high and low tensions. We also directly observed that the degree of
      platination of DNA strongly depends on the concentration of sodium chloride as
      required for cisplatin's intracellular activity. Our study shows that
      micromanipulation techniques accurately reveal the degree of chemical
      modification of DNA which can be used for a new type of structure-sensitive
      biosensors.

PMID- 19113673
TI  - Molecular dynamics characterization of protein crystal contacts in aqueous
      solutions.
AB  - We employ nonequilibrium molecular dynamics simulation to characterize the
      effective interactions between lysozyme molecules involved in the formation of
      two hydrophobic crystal contacts. We show that the effective interactions between
      crystal contacts do not exceed a few kT, the range of the attractive part of the
      potential is less than 4 angstroms, and, within this range, there is a
      significant depletion of water density between two protein contacts. Our findings
      highlight the different natures of protein crystallization and protein
      recognition processes.

PMID- 19113674
TI  - Temporal analysis of active and passive transport in living cells.
AB  - The cellular cytoskeleton is a fascinating active network, in which Brownian
      motion is intercepted by distinct phases of active transport. We present a time
      resolved statistical analysis dissecting phases of directed motion out of
      otherwise diffusive motion of tracer particles in living cells. The distribution
      of active lifetimes is found to decay exponentially with a characteristic time
      tauA = 0.65 s. The velocity distribution of active events exhibits several peaks,
      in agreement with a discrete number of motor proteins acting collectively.

PMID- 19113675
TI  - New dynamical window onto the landscape for forced protein unfolding.
AB  - The unfolding of a protein by the application of an external force pulling two
      atoms of the protein can be detected by atomic force and optical tweezers
      technologies as have been broadly demonstrated in the past decade. Variation of
      the applied force results in a modulation of the free-energy barrier to unfolding
      and thus, the rate of the process, which is often assumed to have single
      exponential kinetics. It has been recently shown that it is experimentally
      feasible, through the use of force clamps, to estimate the distribution of
      unfolding times for a population of proteins initially in the native state. In
      this Letter we show how the analysis of such distributions under a range of
      forces can provide unique information about the underlying free-energy surface
      such as the height of the free-energy barrier, the preexponential factor and the
      force dependence of the unfolding kinetics without resorting to ad hoc kinetic
      models.

PMID- 19113676
TI  - Temporal precision of spike response to fluctuating input in pulse-coupled
      networks of oscillating neurons.
AB  - A single neuron is known to generate almost identical spike trains when the same
      fluctuating input is repeatedly applied. Here, we study the reliability of spike
      firing in a pulse-coupled network of oscillator neurons receiving fluctuating
      inputs. We can study the precise responses of the network as synchronization
      between uncoupled copies of the network by a common noisy input. To study the
      noise-induced synchronization between networks, we derive a self-consistent
      equation for the distribution of spike-time differences between the networks.
      Solving this equation, we elucidate how the spike precision changes as a function
      of the coupling strength.

PMID- 19113677
TI  - Motional coherence in fluid phospholipid membranes.
AB  - We report a high energy-resolution neutron backscattering study, combined with in
      situ diffraction, to investigate slow molecular motions on nanosecond time scales
      in the fluid phase of phospholipid bilayers of 1,2-dimyristoyl-sn-glycero-3
      phoshatidylcholine. A cooperative structural relaxation process was observed.
      From the in-plane scattering vector dependence of the relaxation rates in
      hydrogenated and deuterated samples, combined with results from a 0.1 micros long
      all-atom molecular dynamics simulation, it is concluded that correlated dynamics
      in lipid membranes occurs over several lipid distances, spanning a time interval
      from pico- to nanoseconds.

PMID- 19113678
TI  - Model for stretching and unfolding the giant multidomain muscle protein using
      single-molecule force spectroscopy.
AB  - Single-molecule manipulation has allowed the forced unfolding of multidomain
      proteins. Here we outline a theory that not only explains these experiments but
      also points out a number of difficulties in their interpretation and makes
      suggestions for further experiments. For titin we reproduce force-extension
      curves, the dependence of break force on pulling speed, and break-force
      distributions and also validate two common experimental views: Unfolding titin Ig
      domains can be explained as stepwise increases in contour length, and increasing
      force peaks in native Ig sequences represent a hierarchy of bond strengths. Our
      theory is valid for essentially any molecule that can be unfolded in atomic force
      microscopy; as a further example, we present force-extension curves for the
      unfolding of RNA hairpins.

PMID- 19113679
TI  - Comment on "regional versus global entanglement in resonating-valence-bond
      states".

PMID- 19113681
TI  - Essay: fifty years of condensed matter physics.
AB  - Since the birth of Physical Review Letters fifty years ago, condensed matter
      physics has seen considerable growth, and both the journal and the field have
      flourished during this period. In this essay, I begin with some general comments
      about condensed matter physics and then give some personal views on the
      conceptual development of the field and list some highlights. The focus is mostly
      on theoretical developments.

PMID- 19113682
TI  - Matter-wave self-imaging by atomic center-of-mass motion induced interference.
AB  - We demonstrate matter-wave self-imaging resulting from atomic center-of-mass
      motion-based interference. We show that non-negligible atomic center-of-mass
      motion and an instantaneous Doppler shift can drastically change the condensate
      momentum distribution, resulting in a periodic collapse and the recurrence of
      condensate diffraction probability as a function of the stationary light-field
      pulsing time. The observed matter-wave self-imaging is characterized by an atomic
      center-of-mass motion induced population amplitude interference in the presence
      of the light field that simultaneously minimizes all high (n>or=1) diffraction
      orders and maximizes the zeroth diffraction component.

PMID- 19113683
TI  - Theory of magnetization plateaux in the Shastry-Sutherland model.
AB  - Motivated by the remarkable properties of SrCu2(BO3) 2 in a magnetic field, we
      use perturbative continuous unitary transformations to determine the
      magnetization plateaux of the Shastry-Sutherland model, unveiling an unexpected
      sequence of plateaux progressively appearing at 2/9, 1/6, 1/9, and 2/15 upon
      increasing the interdimer coupling. We predict that a 1/6 plateau should be
      present in SrCu2(BO3)2, even if residual interactions beyond the Shastry
      Sutherland are strong enough to modify the other plateaux below 1/3. The method
      is extended to calculate the magnetization profile within the plateaux, leading
      to a local structure around triplons that agrees with NMR results on SrCu2(BO3)
      2.

PMID- 19113684
TI  - Bragg spectroscopy of a strongly interacting Fermi gas.
AB  - We present a comprehensive study of the Bose-Einstein condensate to Bardeen
      Cooper-Schrieffer (BEC-BCS) crossover in fermionic 6Li using Bragg spectroscopy.
      A smooth transition from molecular to atomic spectra is observed with a clear
      signature of pairing at and above unitarity. These spectra probe the dynamic and
      static structure factors of the gas and provide a direct link to two-body
      correlations. We have characterized these correlations and measured their density
      dependence across the broad Feshbach resonance at 834 G.

PMID- 19113685
TI  - Demonstration of a quantum nondemolition sum gate.
AB  - The sum gate is the canonical two-mode gate for universal quantum computation
      based on continuous quantum variables. It represents the natural analogue to a
      qubit C-NOT gate. In addition, the continuous-variable gate describes a quantum
      nondemolition (QND) interaction between the quadrature components of two light
      modes. We experimentally demonstrate a QND sum gate, employing the scheme by R.
      Filip, P. Marek, and U. L. Andersen [Phys. Rev. A 71, 042308
      (2005)10.1103/PhysRevA.71.042308], solely based on off-line squeezed states,
      homodyne measurements, and feedforward. The results are verified by
      simultaneously satisfying the criteria for QND measurements in both conjugate
      quadratures.

PMID- 19113686
TI  - Quantum critical behavior in strongly interacting Rydberg gases.
AB  - We study the appearance of correlated many-body phenomena in an ensemble of atoms
      driven resonantly into a strongly interacting Rydberg state. The ground state of
      the Hamiltonian describing the driven system exhibits a second order quantum
      phase transition. We derive the critical theory for the quantum phase transition
      and show that it describes the properties of the driven Rydberg system in the
      saturated regime. We find that the suppression of Rydberg excitations known as
      blockade phenomena exhibits an algebraic scaling law with a universal exponent.

PMID- 19113687
TI  - Classical simulation of infinite-size quantum lattice systems in two spatial
      dimensions.
AB  - We present an algorithm to simulate two-dimensional quantum lattice systems in
      the thermodynamic limit. Our approach builds on the projected entangled-pair
      state algorithm for finite lattice systems [F. Verstraete and J. I. Cirac,
      arxiv:cond-mat/0407066] and the infinite time-evolving block decimation algorithm
      for infinite one-dimensional lattice systems [G. Vidal, Phys. Rev. Lett. 98,
      070201 (2007)10.1103/PhysRevLett.98.070201]. The present algorithm allows for the
      computation of the ground state and the simulation of time evolution in infinite
      two-dimensional systems that are invariant under translations. We demonstrate its
      performance by obtaining the ground state of the quantum Ising model and
      analyzing its second order quantum phase transition.

PMID- 19113688
TI  - Size and energy scaling of nonstatistical vibrational quantum states.
AB  - Polyatomic molecules are generally believed to behave more statistically as the
      number of vibrational modes increases. We show that even at the dissociation
      energy, low mode populations result in many nonstatistical quantum states. We
      derive a scaling relation for the number of nonstatistical states as a function
      of molecular size. In molecules with more than 6 atoms this model predicts that
      the majority of states are nonstatistical at dissociation.

PMID- 19113689
TI  - Experimental constraints on a dark matter origin for the DAMA annual modulation
      effect.
AB  - A claim for evidence of dark matter interactions in the DAMA experiment has been
      recently reinforced. We employ a new type of germanium detector to conclusively
      rule out a standard isothermal galactic halo of weakly interacting massive
      particles as the explanation for the annual modulation effect leading to the
      claim. Bounds are similarly imposed on a suggestion that dark pseudoscalars might
      lead to the effect. We describe the sensitivity to light dark matter particles
      achievable with our device, in particular, to next-to-minimal supersymmetric
      model candidates.

PMID- 19113690
TI  - Singularities in loop quantum cosmology.
AB  - We show that simple scalar field models can give rise to curvature singularities
      in the effective Friedmann dynamics of loop quantum cosmology (LQC). We find
      singular solutions for spatially flat Friedmann-Robertson-Walker cosmologies with
      a canonical scalar field and a negative exponential potential, or with a phantom
      scalar field and a positive potential. While LQC avoids big bang or big rip type
      singularities, we find sudden singularities where the Hubble rate is bounded, but
      the Ricci curvature scalar diverges. We conclude that the effective equations of
      LQC are not in themselves sufficient to avoid the occurrence of curvature
      singularities.

PMID- 19113691
TI  - Can we avoid dark energy?
AB  - The idea that we live near the center of a large, nonlinear void has attracted
      attention recently as an alternative to dark energy or modified gravity. We show
      that an appropriate void profile can fit both the latest cosmic microwave
      background and supernova data. However, this requires either a fine-tuned
      primordial spectrum or a Hubble rate so low as to rule these models out. We also
      show that measurements of the radial baryon acoustic scale can provide very
      strong constraints. Our results present a serious challenge to void models of
      acceleration.

PMID- 19113692
TI  - Stringent null constraint on cosmological evolution of the proton-to-electron
      mass ratio.
AB  - We present a strong constraint on variation of the proton-to-electron mass ratio
      mu over cosmological time scales using molecular hydrogen transitions in optical
      quasar spectra. Using high quality spectra of quasars Q0405-443, Q0347-383, and
      Q0528-250, variation in micro relative to the present day value is limited to
      Deltamicro/micro=(2.6+/-3.0)x10;{-6}. We reduce systematic errors compared to
      previous works by substantially improving the spectral wavelength calibration
      method and by fitting absorption profiles to the forest of hydrogen Lyman alpha
      transitions surrounding each H2 transition. Our results are consistent with no
      variation, and inconsistent with a previous approximately 4sigma detection of mu
      variation involving Q0405-443 and Q0347-383. If the results of this work and
      those suggesting that alpha may be varying are both correct, then this would tend
      to disfavor certain grand unification models.

PMID- 19113693
TI  - Measurement of the time-dependent CP asymmetries in B0-->K(S)(0)rho(0)gamma
      decays.
AB  - We report the first measurement of time-dependent CP asymmetry in B(0)-
      >K(S)(0)rho(0)gamma decays based on 657 x 10(6) BB pairs collected with the Belle
      detector at the KEKB asymmetric-energy collider. We measure the CP-violating
      parameter S_{K_{S};{0}rho;{0}gamma}=0.11+/-0.33(stat)-0.09+0.05(syst) from a
      signal of 212+/-17 events. We also obtain the effective direct CP-violating
      parameter A{eff}=0.05+/-0.18(stat)+/-0.06(syst) for mK(S)0pi+pi- <1.8 GeV/c(2)
      and 0.6 GeV/c(2)<m pi+pi- <0.9 GeV/c2.

PMID- 19113698
TI  - Identification of a scalar glueball.
AB  - We perform a coupled channel study of the meson-meson S waves with isospin (I) 0
      and 1/2 up to 2 GeV. A new approach is derived that allows one to include the
      many channels pipi, KK[over ], etaeta, sigmasigma, etaeta; eta; eta; , rhorho,
      omegaomega, omegavarphi, varphivarphi, a(1)pi, and pipi with still few free
      parameters. It follows that coupled channel dynamics is strong and cannot be
      neglected in order to study resonance properties in the region 1.4-1.6 GeV. All
      the resonances with masses below 2 GeV and I=0 and 1/2 are generated. We identify
      the f(0)(1710) and an important contribution to the f (0)(1500) as an unmixed
      glueball. This is based on an accurate agreement of our results with predictions
      of lattice QCD and the chiral suppression of the coupling of a scalar glueball to
      q[over ]q. Another pole, mainly corresponding to the f_{0}(1370), is a pure octet
      state.

PMID- 19113700
TI  - Production and beta decay of rp-process nuclei 96Cd, 98In, and 100Sn.
AB  - The beta-decay properties of the N=Z nuclei 96Cd, 98In, and 100Sn have been
      studied. These nuclei were produced at the National Superconducting Cyclotron
      Laboratory by fragmenting a 120 MeV/nucleon 112Sn primary beam on a Be target.
      The resulting radioactive beam was filtered in the A1900 and the newly
      commissioned Radio Frequency Fragment Separator to achieve a purity level
      suitable for decay studies. The observed production cross sections of these
      nuclei are lower than predicted by factors of 10-30. The half-life of 96Cd, which
      was the last experimentally unknown waiting point half-life of the astrophysical
      rp process, is 1.03_{-0.21};{+0.24} s. The implications of the experimental
      T_{1/2} value of 96Cd on the abundances predicted by rp process calculations and
      the origin of A=96 isobars such as 96Ru are explored.

PMID- 19113701
TI  - Masses and charge radii of 17-22Ne and the two-proton-halo candidate 17Ne.
AB  - High-precision mass and charge radius measurements on ;{17-22}Ne, including the
      proton-halo candidate 17Ne, have been performed with Penning trap mass
      spectrometry and collinear laser spectroscopy. The 17Ne mass uncertainty is
      improved by factor 50, and the charge radii of ;{17-19}Ne are determined for the
      first time. The fermionic molecular dynamics model explains the pronounced
      changes in the ground-state structure. It attributes the large charge radius of
      17Ne to an extended proton configuration with an s;{2} component of about 40%. In
      18Ne the smaller radius is due to a significantly smaller s;{2} component. The
      radii increase again for ;{19-22}Ne due to cluster admixtures.

PMID- 19113702
TI  - Ultrafast laser-driven excitation dynamics in ne: an ab initio time-dependent R
      matrix approach.
AB  - An attosecond pump-probe scheme that combines the use of a free-electron laser
      pulse with an ultrashort pulse is applied in order to explore the ultrafast
      excitation dynamics in Ne. We describe the multielectron dynamics using a new
      nonperturbative time-dependent R-matrix theory. This theory enables the
      interaction of ultrashort light fields with multielectron atoms and atomic ions
      to be determined from first principles. By probing the emission of an inner 2s
      electron from Ne we are also able to study the bound state population dynamics
      during the free-electron laser pulse.

PMID- 19113703
TI  - Parametrization of the two-electron reduced density matrix for its direct
      calculation without the many-electron wave function.
AB  - Parametrization of a molecular two-electron reduced density matrix (2-RDM)
      enables energies and properties to be directly computed at a highly efficient
      computational cost. In this Letter an improved 2-RDM parametrization yields
      energies and properties that are markedly better than those calculated with a
      similar computational scaling by traditional ab initio methods. Computed 2-RDMs
      very nearly satisfy well-known N-representability conditions. Applications are
      made to ground-state energies of several molecules and equilibrium bond distances
      and harmonic frequencies of HF, F2, and CO. The method for single-bond breaking
      in HF and CH4 yields similar accuracy at equilibrium and nonequilibrium
      geometries.

PMID- 19113704
TI  - Most typical 1 ratio 2 resonant perturbation of the hydrogen atom by weak
      electric and magnetic fields.
AB  - We study a perturbation of the hydrogen atom by small homogeneous static electric
      and magnetic fields in a specific mutual alignment with angle approximately pi/3
      which results in the 1 ratio 2 resonance of the linearized Keplerian n-shell
      approximation. The bifurcation diagram of the classical integrable approximation
      has for most such field configurations the same typical structure that we
      describe. The structure of the corresponding quantum energy spectrum, which we
      describe in detail, is in certain ways an analogue of the well-known degeneracy
      found by Herrick [Phys. Rev. A 26, 323 (1982)] for the quadratic Zeeman effect.

PMID- 19113695
TI  - Search for the standard model Higgs boson in the missing energy and acoplanar b
      jet topology at sqrt[s]=1.96 TeV.
AB  - We report a search for the standard model Higgs boson in the missing energy and
      acoplanar b-jet topology, using an integrated luminosity of 0.93 fb;{-1} recorded
      by the D0 detector at the Fermilab Tevatron pp[over ] Collider. The analysis
      includes signal contributions from pp[over ]-->ZH-->nunu[over ]bb[over ], as well
      as from WH production in which the charged lepton from the W boson decay is
      undetected. Neural networks are used to separate signal from background. In the
      absence of a signal, we set limits on sigma(pp[over ]-->VH)xB(H-->bb[over ]) at
      the 95% C.L. of 2.6-2.3 pb, for Higgs boson masses in the range 105-135 GeV,
      where V=W, Z. The corresponding expected limits range from 2.8 to 2.0 pb.

PMID- 19113705
TI  - Suppression of decoherence in fast-atom diffraction at surfaces.
AB  - Scattering of fast neutral atoms with keV kinetic energies at alkali-halide
      surfaces under grazing angles displays intriguing diffraction patterns. The
      surprisingly strong persistence of quantum coherence despite the impulsive
      interaction with an environment at solid state density and elevated temperatures
      raises fundamental questions such as to the suppression of decoherence and of the
      quantum-to-classical crossover. We present an ab initio simulation of the quantum
      diffraction of fast helium beams at a LiF (100) surface in the 110 direction and
      compare with recent experimental diffraction data. From the quantitative
      reconstruction of diffraction images the vertical LiF-surface reconstruction, or
      buckling, can be determined.

PMID- 19113706
TI  - Quantum illumination with Gaussian states.
AB  - An optical transmitter irradiates a target region containing a bright thermal
      noise bath in which a low-reflectivity object might be embedded. The light
      received from this region is used to decide whether the object is present or
      absent. The performance achieved using a coherent-state transmitter is compared
      with that of a quantum-illumination transmitter, i.e., one that employs the
      signal beam obtained from spontaneous parametric down-conversion. By making the
      optimum joint measurement on the light received from the target region together
      with the retained spontaneous parametric down-conversion idler beam, the quantum
      illumination system realizes a 6 dB advantage in the error-probability exponent
      over the optimum reception coherent-state system. This advantage accrues despite
      there being no entanglement between the light collected from the target region
      and the retained idler beam.

PMID- 19113707
TI  - Controlled generation of squeezed states of microwave radiation in a
      superconducting resonant circuit.
AB  - Superconducting oscillators have been successfully used for quantum control and
      readout devices in conjunction with superconducting qubits. Also, squeezed states
      can improve the accuracy of measurements to subquantum, or at least subthermal,
      levels. Here, we show theoretically how to produce squeezed states of microwave
      radiation in a superconducting oscillator with tunable parameters. Its resonance
      frequency can be changed by controlling an rf SQUID inductively coupled to the
      oscillator. By repeatedly shifting the resonance frequency between any two
      values, it is possible to produce squeezed and subthermal states of the
      electromagnetic field in the (0.1-10) GHz range, even when the relative frequency
      change is small. We propose experimental protocols for the verification of
      squeezed state generation, and for their use to improve the readout fidelity when
      such oscillators serve as quantum transducers.

PMID- 19113708
TI  - Coherent water window x ray by phase-matched high-order harmonic generation in
      neutral media.
AB  - We demonstrate the generation of a coherent water window x ray by extending the
      plateau region of high-order harmonics under a neutral-medium condition. The
      maximum harmonic photon energies attained are 300 and 450 eV in Ne and He,
      respectively. Our proposed generation scheme, combining a 1.6 microm laser driver
      and a neutral Ne gas medium, is efficient and scalable in output yields of the
      water window x ray. Thus, the precept of the design parameter for a single-shot
      live-cell imaging by contact microscopy is presented.

PMID- 19113709
TI  - Homoclinic snaking in a semiconductor-based optical system.
AB  - We report on experimental observations of homoclinic snaking in a vertical-cavity
      semiconductor optical amplifier. Our observations in a quasi-one-dimensional and
      two-dimensional configurations agree qualitatively well with what is expected
      from recent theoretical and numerical studies. In particular, we show the
      bifurcation sequence leading to a snaking bifurcation diagram linking single
      localized states to "localized patterns" or clusters of localized states and
      demonstrate a parameter region where cluster states are inhibited.

PMID- 19113699
TI  - System-size independence of directed flow measured at the BNL relativistic heavy
      ion collider.
AB  - We measure directed flow (v_{1}) for charged particles in Au+Au and Cu+Cu
      collisions at sqrt[s_{NN}]=200 and 62.4 GeV, as a function of pseudorapidity
      (eta), transverse momentum (p_{t}), and collision centrality, based on data from
      the STAR experiment. We find that the directed flow depends on the incident
      energy but, contrary to all available model implementations, not on the size of
      the colliding system at a given centrality. We extend the validity of the
      limiting fragmentation concept to v_{1} in different collision systems, and
      investigate possible explanations for the observed sign change in v_{1}(p_{t}).

PMID- 19113710
TI  - Metamaterial analog of electromagnetically induced transparency.
AB  - We demonstrate a classical analog of electromagnetically induced transparency in
      a planar metamaterial. We show that pulses propagating through such metamaterials
      experience considerable delay. The thickness of the structure along the direction
      of wave propagation is much smaller than the wavelength, which allows successive
      stacking of multiple metamaterial slabs leading to increased transmission and
      bandwidth.

PMID- 19113696
TI  - Search for the Higgs boson produced in association with Z-->l+l in pp collisions
      at sqrt[s]=1.96 TeV.
AB  - We present a search for the Higgs boson in the process qq-->ZH-->l;{+}l;{
      }bb[over ]. The analysis uses an integrated luminosity of 1 fb;{-1} of pp[over ]
      collisions produced at sqrt[s]=1.96 TeV and accumulated by the upgraded Collider
      Detector at Fermilab (CDF II). We employ artificial neural networks both to
      correct jets mismeasured in the calorimeter and to distinguish the signal
      kinematic distributions from those of the background. We see no evidence for
      Higgs boson production, and set 95% C.L. upper limits on sigma{ZH}B(H-->bb[over
      ]), ranging from 1.5 to 1.2 pb for a Higgs boson mass (m{H}) of 110 to 150
      GeV/c(2).

PMID- 19113711
TI  - Experimental demonstration of hyperbolic patterns.
AB  - We give experimental evidence of hyperbolic patterns in a nonlinear optical
      resonator. Such transverse patterns are a new kind of 2D dissipative structures,
      characterized by a distribution of the active modes along hyperbolas in the
      transverse wave-vector domain, in contrast with the usual (elliptic) patterns
      where the active modes distribute along rings. The hyperbolic character is
      realized by manipulating diffraction inside the optical resonator with
      cylindrical lenses. We also investigate theoretically hyperbolic patterns in
      corresponding Swift-Hohenberg models.

PMID- 19113694
TI  - Search for supersymmetry in pp collisions at sqrt[s]=1.96 TeV Using the trilepton
      signature for chargino-neutralino production.
AB  - We use the three lepton and missing energy trilepton signature to search for
      chargino-neutralino production with 2.0 fb;{-1} of integrated luminosity
      collected by the CDF II experiment at the Tevatron pp[over ] collider. We expect
      an excess of approximately 11 supersymmetric events for a choice of parameters of
      the mSUGRA model, but our observation of 7 events is consistent with the standard
      model expectation of 6.4 events. We constrain the mSUGRA model of supersymmetry
      and rule out chargino masses up to 145 GeV/c;{2} for a specific choice of
      parameters.

PMID- 19113712
TI  - Self-organization of topological defects due to applied constraints.
AB  - While topological defects are essential to our understanding of self-organizing
      periodic systems, little is known about how these systems respond when their
      defects are subjected to geometrical constraints. In an experiment on spatially
      modulated thermal convection patterns, we observe that applied geometrical
      constraints bind topological defects into robust self-localized structures that
      evolve through aggregation, annihilation, and self-replication. We demonstrate
      that this unexpected cooperative response to the modulation is a natural
      consequence of three generic elements: phase locking, symmetry breaking, and
      spatial resonance. Our work provides new insights into the interplay between
      order, chaos, and control in self-organizing systems.

PMID- 19113713
TI  - Selection of nonequilibrium overlimiting currents: universal depletion layer
      formation dynamics and vortex instability.
AB  - The ion flux dynamics across a straight nanoslot is imaged to understand the
      nonequilibrium phenomenon of overlimiting current density across a nanoporous
      membrane. With a slow ac field, an ion-depletion front is generated
      intermittently from one end of the nanochannel, and a vortex instability first
      predicted by Rubinstein, Staude, and Kedem [Desalination 69, 101
      (1988).10.1016/0011-9164(88)80013-4] is found to arrest the self-similar
      diffusive front growth. This electrokinetic instability evolves into a stationary
      interfacial vortex array that specifies the overlimiting current, independent of
      external stirring or convective flow.

PMID- 19113714
TI  - Shear-induced diffusion of platelike particles in microchannels.
AB  - We exploit the recent developments of microfluidic technologies to investigate
      the collective shear-induced diffusion in suspensions of micron-sized particles.
      Whereas spherical particles do not diffuse on the time scale of our experiments,
      the results with platelike clay particles show a strong cross-stream shear
      induced diffusivity at low volume fraction (phi{0}<or=0.01). Moreover, we find a
      linear dependence of the collective diffusion coefficient with the average shear
      rate (in the range 10;{2}-10;{4} s;{-1}) and the particle concentration. These
      data are in good agreement with previous experimental and theoretical results for
      spheres when rescaled with the particle number density.

PMID- 19113715
TI  - Shock front width and structure in supersonic granular flows.
AB  - The full structure of a shock front around a blunt body in a quasi-two
      dimensional granular flow is studied. Two features, a large density gradient and
      a very small thickness of the front, characterize this shock and make it
      different from shocks in molecular gases. Both of these features can be
      understood using a modified version of the granular kinetic theory. Our model
      separates the particles into two subpopulations: fast particles having
      experienced no collisions and randomly moving particles. This separation is
      motivated by direct measurements of the particle velocities which show a bimodal
      distribution. Our results not only shed new light on the use of the granular
      kinetic theory under extreme conditions (shock formation) but bring new insight
      into the physics of shocks in general.

PMID- 19113716
TI  - Transverse-coherence properties of the free-electron-laser FLASH at DESY.
AB  - A general theoretical approach based on the decomposition of statistical fields
      into a sum of independently propagating transverse modes was used for the
      analysis of the coherence properties of the new free-electron laser source FLASH
      operated at 13.7 nm wavelength. The analysis shows that several transverse modes
      are contributing to the total radiation field of FLASH. The results of
      theoretical calculations are compared with measurements using Young's double-slit
      experiment. The coherence lengths in the horizontal and in the vertical
      directions 20 m downstream from the source are estimated at 300 and 250 microm,
      respectively.

PMID- 19113717
TI  - Collision-driven negative-energy waves and the weibel instability of a
      relativistic electron beam in a quasineutral plasma.
AB  - A new model describing the Weibel instability of a relativistic electron beam
      propagating through a resistive plasma is developed. For finite-temperature
      beams, a new class of negative-energy magnetosound waves is identified, whose
      growth due to collisional dissipation destabilizes the beam-plasma system even
      for high beam temperatures. We perform 2D and 3D particle-in-cell simulations and
      show that in 3D geometry the Weibel instability persists even for collisionless
      background plasma. The anomalous plasma resistivity in 3D is caused by the two
      stream instability.

PMID- 19113697
TI  - Measurement of the single-top-quark production cross section at CDF.
AB  - We report a measurement of the single-top-quark production cross section in 2.2
      fb;{-1} of pp collision data collected by the Collider Detector at Fermilab at
      sqrt[s]=1.96 TeV. Candidate events are classified as signal-like by three
      parallel analyses which use likelihood, matrix element, and neural network
      discriminants. These results are combined in order to improve the sensitivity. We
      observe a signal consistent with the standard model prediction, but inconsistent
      with the background-only model by 3.7 standard deviations with a median expected
      sensitivity of 4.9 standard deviations. We measure a cross section of 2.2(
      0.6)(+0.7)(stat+syst) pb, extract the Cabibbo-Kobayashi-Maskawa matrix-element
      value |V(tb)|=0.88(-0.12)(+0.13)(stat+syst)+/-0.07(theory), and set the limit
      |V(tb)|>0.66 at the 95% C.L.

PMID- 19113718
TI  - Compressibility effects in the dynamics of the reversed-field pinch.
AB  - We study the reversed-field pinch through the numerical solution of the
      compressible magnetohydrodynamic equations. Two cases are investigated: In the
      first case the pressure is derived from an adiabatic condition, and in the second
      case the pressure equation includes heating terms due to resistivity and
      viscosity. In the adiabatic case a single helicity state is observed, and the
      reversed-field pinch configuration is formed for short time intervals and is
      finally lost. In the nonadiabatic case the system reaches a multiple helicity
      state, and the reversal parameter remains negative for a longer time. The results
      show the importance of compressibility in determining the large scale dynamics of
      the system.

PMID- 19113720
TI  - Unusual states of vortex matter in mixtures of Bose-Einstein condensates on
      rotating optical lattices.
AB  - In a single-component superfluid under rotation a broken symmetry in the order
      parameter space results in a broken translational symmetry in real space: a
      vortex lattice. If translational symmetry is restored, the phase of the order
      parameter disorders and thus the broken symmetry in the order parameter space is
      also restored. We show that for Bose-Einstein condensate mixtures in optical
      lattices with negative dissipationless drag, a new situation arises. This state
      is a modulated vortex liquid which breaks translational symmetry in the direction
      transverse to the rotation vector.

PMID- 19113719
TI  - Laboratory observation of electron phase-space holes during magnetic
      reconnection.
AB  - We report the observation of large-amplitude, nonlinear electrostatic structures,
      identified as electron phase-space holes, during magnetic reconnection
      experiments on the Versatile Toroidal Facility at MIT. The holes are positive
      electric potential spikes, observed on high-bandwidth ( approximately 2 GHz)
      Langmuir probes. Investigations with multiple probes establish that the holes
      travel at or above the electron thermal speed and have a three-dimensional,
      approximately spherical shape, with a scale size approximately 2 mm. This
      corresponds to a few electron gyroradii, or many tens of Debye lengths, which is
      large compared to holes considered in simulations and observed by satellites,
      whose length scale is typically only a few Debye lengths. Finally, a statistical
      study over many discharges confirms that the holes appear in conjunction with the
      large inductive electric fields and the creation of energetic electrons
      associated with the magnetic energy release.

PMID- 19113721
TI  - Devil's staircase of facets on the surface of 4He crystals.
AB  - According to Landau, at T=0 the equilibrium crystal surface consists of an
      infinite number of facets lying in all directions with rational Miller indices
      the so-called devil's staircase phenomenon. We have discovered 11 new types of
      facets on the surface of 4He crystals, in addition to the three observed before.
      Some of the new facets are of very high order, lying at angles as small as 4
      degrees to the basal c facet, thus forming the predicted devil's staircase. The
      estimated step energies depend rather weakly on interplanar distance which we
      explain by the strong anisotropy of the steps.

PMID- 19113722
TI  - Crack propagation through phase-separated glasses: effect of the characteristic
      size of disorder.
AB  - We perform fracture experiments on nanoscale phase-separated glasses and measure
      crack surface roughness by atomic force microscopy. The ability of tuning the
      phase domain size by thermal treatment allows us to test thoroughly the
      predictions of crack front depinning models about the scaling properties of crack
      surface roughness. It appears that, in the range of validity of these depinning
      models developed for the fracture of brittle materials, our experimental results
      show a quantitative agreement with theoretical predictions: Beyond the
      characteristic size of disorder, the roughness of crack surfaces obeys the
      logarithmic scaling early predicted by Ramanathan, Ertas, and Fisher [Phys. Rev.
      Lett. 79, 873 (1997)].

PMID- 19113723
TI  - Sixfold-coordinated amorphous polymorph of SiO2 under high pressure.
AB  - We have developed synchrotron x-ray absorption and diffraction techniques for
      measuring the density and structure of noncrystalline materials at high pressures
      and have applied them to studying the behavior of SiO2 glass. The density,
      coordination number, and Si-O bond length at a pressure of 50 GPa were measured
      to be 4.63 g/cm;{3}, 6.3, and 1.71 A, respectively. Based on the density data
      measured in this study and the sound velocity data available in the literature,
      the bulk modulus at 50 GPa was estimated to be 390 GPa, which is consistent with
      the pressure dependence of the density in the vicinity of 50 GPa. These results,
      together with the knowledge from our exploratory study, suggest that SiO2 glass
      behaves as a single amorphous polymorph having a sixfold-coordinated structure at
      pressures above 40-45 GPa up to at least 100 GPa.

PMID- 19113724
TI  - Dynamic arrest in polymer melts: competition between packing and intramolecular
      barriers.
AB  - We present molecular dynamics simulations of a simple model for polymer melts
      with intramolecular barriers. We investigate structural relaxation as a function
      of the barrier strength. Dynamic correlators can be consistently analyzed within
      the framework of the mode coupling theory of the glass transition. Control
      parameters are tuned in order to induce a competition between general packing
      effects and polymer-specific intramolecular barriers as mechanisms for dynamic
      arrest. This competition yields unusually large values of the so-called mode
      coupling theory exponent parameter and rationalizes qualitatively different
      observations for simple bead-spring and realistic polymers. The systematic study
      of the effect of intramolecular barriers presented here also establishes a
      fundamental difference between the nature of the glass transition in polymers and
      in simple glass formers.

PMID- 19113725
TI  - Experimental observation of the Anderson metal-insulator transition with atomic
      matter waves.
AB  - We realize experimentally an atom-optics quantum-chaotic system, the
      quasiperiodic kicked rotor, which is equivalent to a 3D disordered system that
      allows us to demonstrate the Anderson metal-insulator transition. Sensitive
      measurements of the atomic wave function and the use of finite-size scaling
      techniques make it possible to extract both the critical parameters and the
      critical exponent of the transition, the latter being in good agreement with the
      value obtained in numerical simulations of the 3D Anderson model.

PMID- 19113726
TI  - Self-organized formation of GaSb/GaAs quantum rings.
AB  - Ring-shaped GaSb/GaAs quantum dots, grown by molecular beam epitaxy, were studied
      using cross-sectional scanning tunneling microscopy. These quantum rings have an
      outer shape of a truncated pyramid with baselengths around 15 nm and heights of
      about 2 nm but are characterized by a clear central opening extending over about
      40% of the outer baselength. They form spontaneously during the growth and
      subsequent continuous capping of GaSb/GaAs quantum dots due to the large strain
      and substantial As-for-Sb exchange reactions leading to strong Sb segregation.

PMID- 19113727
TI  - Phase transformation near the classical limit of stability.
AB  - Successful theories of phase transformation processes include classical
      nucleation theory, which envisions a local equilibrium between coexisting phases,
      and nonequilibrium kinetic cluster theories. Using computer simulations of the
      magnetization reversal of the Ising model in three different ensembles we make
      quantitative connections between these physical pictures. We show that the
      critical nucleus size of classical nucleation theory is strongly correlated with
      a dynamical measure of metastability, and that the metastable phase persists to
      thermodynamic conditions previously thought of as unstable.

PMID- 19113728
TI  - Scattering of plasmons at the intersection of two metallic nanotubes:
      implications for tunneling.
AB  - We study theoretically the plasmon scattering at the intersection of two metallic
      carbon nanotubes. We demonstrate that, for a small angle of crossing theta<<1,
      the transmission coefficient is an oscillatory function of lambda/theta, where
      lambda is the interaction parameter of the Luttinger liquid in an individual
      nanotube. We calculate the tunnel density of states nu(omega,x) as a function of
      energy omega and distance x from the intersection. In contrast with a single
      nanotube, we find that, in the geometry of crossed nanotubes, conventional
      "rapid" oscillations in nu(omega,x) due to the plasmon scattering acquire an
      aperiodic "slow-breathing" envelope which has lambda/theta nodes.

PMID- 19113729
TI  - Novel quantum criticality in CeRu2Si2 near absolute zero observed by thermal
      expansion and magnetostriction.
AB  - We report linear thermal expansion and magnetostriction measurements for CeRu2Si2
      in magnetic fields up to 52.6 mT and at temperatures down to 1 mK. At high
      temperatures, this compound showed Landau-Fermi-liquid behavior: The linear
      thermal expansion coefficient and the magnetostriction coefficient were
      proportional to the temperature and magnetic field, respectively. In contrast, a
      pronounced non-Fermi-liquid effect was found below 50 mK. The negative
      contribution of thermal expansion and magnetostriction suggests the existence of
      an additional quantum critical point.

PMID- 19113730
TI  - Homopolar bond formation in ZnV2O4 close to a metal-insulator transition.
AB  - Electronic structure calculations for spinel vanadate ZnV2O4 show that partial
      electronic delocalization in this system leads to a structural instability, with
      the formation of V-V dimers along the [011] and [101] directions, and readily
      accounts for the intriguing magnetic structure of this material. The formation of
      V-V bonds is a consequence of the proximity to the itinerant-electron boundary
      and is not related to orbital ordering. We discuss how this mechanism naturally
      couples charge and lattice degrees of freedom in magnetic insulators close to
      such a crossover.

PMID- 19113731
TI  - T=0 heavy-fermion quantum critical point as an orbital-selective Mott transition.
AB  - We describe the T=0 quantum phase transition in heavy-fermion systems as an
      orbital-selective Mott transition (OSMT) using a cluster extension of dynamical
      mean-field theory. This transition is characterized by the emergence of a new
      intermediate energy scale corresponding to the opening of a pseudogap and the
      vanishing of the low-energy hybridization between light and heavy electrons. We
      identify the fingerprint of Mott physics in heavy electron systems with the
      appearance of surfaces in momentum space where the self-energy diverges and we
      derive experimental consequences of this scenario for photoemission,
      compressibility, optical conductivity, susceptibility, and specific heat.

PMID- 19113732
TI  - Breakdown of Landau theory in overdoped cuprates near the onset of
      superconductivity.
AB  - We use the functional renormalization group to analyze the temperature dependence
      of the quasiparticle scattering rates in the two-dimensional Hubbard model below
      half-filling. Using a band structure appropriate to overdoped Tl2Ba2CuO6+x we
      find a strongly angle-dependent term linearly dependent on temperature which
      derives from an increasing scattering vertex as the energy scale is lowered. This
      behavior agrees with recent experiments and confirms earlier conclusions on the
      origin of the breakdown of the Landau-Fermi liquid near the onset of
      superconductivity.

PMID- 19113733
TI  - Influence of disorder on electron-hole pair condensation in graphene bilayers.
AB  - Graphene bilayers can condense into a state with spontaneous interlayer phase
      coherence that supports dissipationless counterflow supercurrents. Here, we
      address the influence of disorder on the graphene bilayer mean field and
      Kosterlitz-Thouless critical temperatures and report on a simple criteria for the
      survival of pair condensation.

PMID- 19113734
TI  - Quantum cavity for spin due to spin-orbit interaction at a metal boundary.
AB  - A quantum cavity for spin is created using a tungsten crystal as substrate of
      high nuclear charge and breaking the structural inversion symmetry through
      deposition of a gold quantum film. Spin- and angle-resolved photoelectron
      spectroscopy shows directly that quantum-well states and the "matrioshka" or
      Russian nested doll Fermi surface of the gold film are spin polarized and spin
      orbit split up to a thickness of at least nine atomic layers. Ferromagnetic
      materials or external magnetic fields are not required, and the quantum film does
      not need to possess a high atomic number as analogous results with silver show.

PMID- 19113735
TI  - Quantitative determination of the nonlinear pinning potential for a magnetic
      domain wall.
AB  - Using microwave currents, we excite resonances of geometrically confined pinned
      domain walls, detecting the resonance by the rectification of the microwave
      current. By applying magnetic fields, the resonance frequency of the domain wall
      oscillator can be tuned over a wide range. Increasing the power leads to a
      redshift due to the nonlinearity of the system. From this frequency shift, we
      directly deduce the quantitative shape of the potential, so that a complete
      characterization of the pinning potential is obtained.

PMID- 19113736
TI  - Origin of the two-dimensional electron gas carrier density at the LaAlO3 on
      SrTiO3 interface.
AB  - Transport measurements of the two-dimensional electron gas at the LaAlO3-SrTiO3
      interface have found a density of carriers much lower than expected from the
      "polar catastrophe" arguments. From a detail density-functional study, we suggest
      how this discrepancy may be reconciled. We find that electrons occupy multiple
      subbands at the interface leading to a rich array of transport properties. Some
      electrons are confined to a single interfacial layer and susceptible to
      localization, while others with small masses and extended over several layers are
      expected to contribute to transport.

PMID- 19113737
TI  - Quantum Hall transition in real space: from localized to extended states.
AB  - Using scanning tunneling spectroscopy in an ultrahigh vacuum at low temperature
      (T=0.3 K) and high magnetic fields (B<or=12 T), we directly probe electronic wave
      functions across an integer quantum Hall transition. In accordance with
      theoretical predictions, we observe the evolution from localized drift states in
      the insulating phases to branched extended drift states at the quantum critical
      point. The observed microscopic behavior close to the extended state indicates
      points of localized quantum tunneling, which are considered to be decisive for a
      quantitative description of the transition.

PMID- 19113738
TI  - Impact of Coulomb scattering on the ultrafast gain recovery in InGaAs quantum
      dots.
AB  - The application of quantum dot (QD) semiconductor optical amplifiers (SOAs) in
      above 100-Gbit Ethernet networks demands an ultrafast gain recovery on time
      scales similar to that of the input pulse approximately 100 GHz repetition
      frequency. Microscopic scattering processes have to act at shortest possible time
      scales and mechanisms speeding up the Coulomb scattering have to be explored,
      controlled, and exploited. We present a microscopic description of the gain
      recovery by coupled polarization- and population dynamics in a thermal
      nonequilibrium situation going beyond rate-equation models and discuss the
      limitations of Coulomb scattering between 0D and 2D-confined quantum states. An
      experiment is designed which demonstrates the control of gain recovery for THz
      pulse trains in InGaAs QD-based SOAs under powerful electrical injection.

PMID- 19113739
TI  - Avalanche-induced current enhancement in semiconducting carbon nanotubes.
AB  - Semiconducting single-wall carbon nanotubes under high electric field stress (
      approximately 10 V/mum) display a remarkable current increase due to avalanche
      generation of free electrons and holes. Unlike other materials, the avalanche
      process in such 1D quantum wires involves access to the third subband and is
      insensitive to temperature but strongly dependent on diameter approximately exp(
      1/d;{2}). Comparison with a theoretical model yields a novel approach to obtain
      the inelastic optical phonon emission length lambda{OP,ems} approximately 15d nm.
      The new results underscore the importance of multiband transport in 1D molecular
      wires.

PMID- 19113740
TI  - Restricted Wiedemann-Franz law and vanishing thermoelectric power in one
      dimensional conductors.
AB  - In one-dimensional conductors with linear E-k dispersion (Dirac systems), intra
      branch thermalization is favored by elastic electron-electron interaction in
      contrast with electron systems with a nonlinear (parabolic) dispersion. We show
      that under external electric fields or thermal gradients, the carrier populations
      of different branches, treated as Fermi gases, have different temperatures as a
      consequence of self-consistent carrier-heat transport. Specifically, in the
      presence of elastic phonon scattering, the Wiedemann-Franz law is restricted to
      each branch with its specific temperature. In addition, thermoelectric power
      vanishes due to electron-hole symmetry, which is validated by experiment.

PMID- 19113741
TI  - Vibronic spectroscopy of an artificial molecule.
AB  - We have performed microwave reflection experiments on a charge-phase qubit
      coupled to an LC oscillator. We find that the system behaves like an artificial
      molecule showing vibronic sideband transitions. The reflected signal is
      determined by a combination of the Franck-Condon principle and resolved-sideband
      cooling or heating of the oscillator.

PMID- 19113742
TI  - Finite frequency noise of a superconductor-ferromagnet quantum point contact.
AB  - We calculate the finite-frequency current noise of a superconductor-ferromagnet
      quantum point contact (SF QPC). This signal is qualitatively affected by the spin
      dependence of interfacial phase shifts acquired by electrons upon reflection on
      the QPC. For a weakly transparent QPC, noise steps appear at frequencies or
      voltages determined directly by the spin dependence of interfacial phase shifts.
      These steps can occur at experimentally accessible temperatures and frequencies.
      Finite-frequency noise is thus a promising tool to characterize the scattering
      properties of a SF QPC.

PMID- 19113743
TI  - Crystal structure and antiferromagnetic order in NdFeAsO1-xFx (x=0.0 and 0.2)
      superconducting compounds from neutron diffraction measurements.
AB  - The transition temperature T{C} approximately 26 K of the recently discovered
      superconductor LaFeAsO1-xFx is extremely sensitive to the lanthanide ion,
      reaching 55 K for the Sm containing oxypnictides. Therefore, it is important to
      determine how the moment on the lanthanide affects the overall magnetism in these
      systems. Here we report a neutron diffraction study of the Nd oxypnictides. Long
      ranged antiferromagnetic order is apparent in NdFeAsO below 1.96 K. Rietveld
      refinement shows that both Fe and Nd magnetic ordering are required to describe
      the observed data with the staggered moment 1.55(4)micro{B}/Nd and
      0.9(1)micro{B}/Fe at 0.3 K. The other structural properties such as the
      tetragonal-orthorhombic distortion are found to be very similar to those in
      LaFeAsO. Neither the magnetic ordering nor the structural distortion occur in the
      superconducting sample NdFeAsO0.80F0.20 at any temperatures down to 1.5 K.

PMID- 19113744
TI  - Neutron-diffraction measurements of magnetic order and a structural transition in
      the parent BaFe2As2 compound of FeAs-based high-temperature superconductors.
AB  - The recent discovery of superconductivity in (Ba,K)Fe2As2, which crystallizes in
      the ThCr2Si2 (122) structure as compared with the LnFeAsO (Ln is lanthanide)
      systems that possess the ZrCuSiAs (1111) structure, demonstrates the exciting
      potential of the FeAs-based materials for high-T{C} superconductivity. Here we
      report neutron diffraction studies that show a tetragonal-to-orthorhombic
      distortion associated with the onset of q=(101) antiferromagnetic order in
      BaFe2As2, with a saturation moment 0.87(3)micro {B} per Fe that is orientated
      along the longer a axis of the ab planes. The simultaneous first-order structural
      and magnetic transition is in contrast with the separated transitions previously
      reported in the 1111-type materials. The orientational relation between magnetic
      alignment and lattice distortion supports a multiorbital nature for the magnetic
      order.

PMID- 19113745
TI  - Optical study of LaO0.9F0.1FeAs: evidence for a weakly coupled superconducting
      state.
AB  - We have studied the reflectance of the recently discovered superconductor
      LaO0.9F0.1FeAs in a wide energy range from the far infrared to the visible
      regime. We report on the observation of infrared active phonons, the plasma edge,
      and possible interband transitions. On the basis of this data and the reported in
      plane penetration depth lambda{L}(0)=254 nm [H. Luetkens, Phys. Rev. Lett. 101,
      097009 (2008)] a disorder sensitive relatively small value of the total electron
      boson coupling constant lambda{tot}=lambda{e-ph}+lambda{e-sp} approximately 0.6+/
      0.35 can be estimated adopting an effective single-band picture.

PMID- 19113746
TI  - Origin of the spin density wave instability in AFe2As2 (A=Ba,Sr) as revealed by
      optical spectroscopy.
AB  - We performed optical spectroscopy measurement on single crystals of BaFe2As2 and
      SrFe2As2, the parent compounds of FeAs-based superconductors. Both are found to
      be quite metallic with fairly large plasma frequencies at high temperature. Upon
      entering the spin-density-wave state, the formation of partial energy gaps was
      clearly observed with the surprising presence of two different energy scales. A
      large part of the Drude component was removed by the gapping of Fermi surfaces.
      Meanwhile, the carrier scattering rate was even more dramatically reduced. We
      elaborate that the spin-density-wave instability is more likely to be driven by
      the Fermi surface nesting of itinerant electrons than a local-exchange mechanism.

PMID- 19113747
TI  - Evidence for two energy gaps in superconducting Ba0.6K0.4Fe2As2 single crystals
      and the breakdown of the Uemura plot.
AB  - We report a detailed investigation on the lower critical field H{c1} of the
      superconducting Ba0.6K0.4Fe2As2 (122) single crystals. A pronounced kink is
      observed on the H{c1}(T) curve, which is attributed to the existence of two
      superconducting gaps. By fitting the data H{c1}(T) to the two-gap BCS model in
      the full temperature region, a small gap of Delta{a}(0)=2.0+/-0.3 meV and a large
      gap of Delta{b}(0)=8.9+/-0.4 meV are obtained. The in-plane penetration depth
      lambda{ab}(0) is estimated to be 105 nm corresponding to a rather large
      superfluid density, which points to the breakdown of the Uemura plot in 122
      superconductors.

PMID- 19113748
TI  - Magnon kinetics and Bose-Einstein condensation studied in phase space.
AB  - Using a novel technique providing simultaneous resolution with respect to the
      wave vector and frequency of magnons, we observed the formation of a Bose
      Einstein condensate documented by the narrowing of the magnon distribution in
      phase space. Based on the measured width of the distribution we determined the
      effective correlation length of the condensate, which appears to be anisotropic,
      reflecting the anisotropy of the magnon dispersion spectrum.

PMID- 19113749
TI  - Giant electrothermal conductivity and spin-phonon coupling in an
      antiferromagnetic oxide.
AB  - The application of weak electric fields ( less, similar 100 V/cm) is found to
      dramatically enhance the lattice thermal conductivity of the antiferromagnetic
      insulator CaMnO3 over a broad range of temperature about the Neel ordering point
      (125 K). The effect is coincident with field-induced detrapping of bound
      electrons, suggesting that phonon scattering associated with short- and long
      ranged antiferromagnetic order is suppressed in the presence of the mobilized
      charge. This interplay between bound charge and spin-phonon coupling might allow
      for the reversible control of spin fluctuations using weak external fields.

PMID- 19113750
TI  - Observation of distinct electron-phonon couplings in gated bilayer graphene.
AB  - A Raman study of a back gated bilayer graphene sample is presented. The changes
      in the Fermi level induced by charge transfer splits the Raman G band, hardening
      its higher component and softening the lower one. These two components are
      associated with the symmetric (S) and antisymmetric vibration (AS) of the atoms
      in the two layers, the later one becoming Raman active due to inversion symmetry
      breaking. The phonon hardening and softening are explained by considering the
      selective coupling of the S and AS phonons with interband and intraband electron
      hole pairs.

PMID- 19113751
TI  - Photoluminescence ring formation in coupled quantum wells: excitonic versus
      ambipolar diffusion.
AB  - In this Letter, we study the diffusion properties of photoexcited carriers in
      coupled quantum wells around the Mott transition. We find that the diffusion of
      unbound electrons and holes is ambipolar and is characterized by a large
      diffusion coefficient, similar to that found in p-i-n junctions. Correlation
      effects in the excitonic phase are found to significantly suppress the carriers'
      diffusion. We show that this difference in diffusion properties gives rise to the
      appearance of a photoluminescence ring pattern around the excitation spot at the
      Mott transition.

PMID- 19113752
TI  - Enhancement of water permeation across a nanochannel by the structure outside the
      channel.
AB  - We used molecular dynamics simulation to study the effect of the external
      structure on water permeation across a single-walled nanochannel. In contrast
      with the macroscopic scenario, the outside structure greatly affects the water
      transport across the nanochannel. Remarkably, the ratio of maximal to minimal
      flux reached a value of about two for different outside structures. These
      findings are expected to be helpful in design of high-flux nanochannels and
      provide an insight into the contribution of the lipid membrane to water
      permeation across biological water channels.

PMID- 19113753
TI  - Correlation between particle motion and Voronoi-cell-shape fluctuations during
      the compaction of granular matter.
AB  - We track particle motions in a granular material subjected to compaction using a
      laser scattering-based imaging method where compaction is achieved through
      thermal cycling. Particle displacements in this jammed fluid correlate strongly
      with rearrangements of the Voronoi cells defining the local environment about the
      particles, similar to previous observations of Rahman on cooled liquids. Our
      observations provide further evidence of commonalities between particle dynamics
      in granular matter close to jamming and supercooled liquids.

PMID- 19113754
TI  - Self-templated nucleation in peptide and protein aggregation.
AB  - Peptides and proteins exhibit a common tendency to assemble into highly ordered
      fibrillar aggregates, whose formation proceeds in a nucleation-dependent manner
      that is often preceded by the formation of oligomeric assemblies. This process
      has received much attention because disordered oligomeric aggregates have been
      associated with neurodegenerative disorders such as Alzheimer's and Parkinson's
      disease. Here we describe a self-templated nucleation mechanism that determines
      the transition between the initial condensation of polypeptide chains into
      disordered assemblies and their reordering into fibrillar structures. The results
      that we present show that at the molecular level this transition is due to the
      ability of polypeptide chains to reorder within oligomers into fibrillar
      assemblies whose surfaces act as templates that stabilize the disordered
      assemblies.

PMID- 19113755
TI  - Spatial variability enhances species fitness in stochastic predator-prey
      interactions.
AB  - We study the influence of spatially varying reaction rates on a spatial
      stochastic two-species Lotka-Volterra lattice model for predator-prey
      interactions using two-dimensional Monte Carlo simulations. The effects of this
      quenched randomness on population densities, transient oscillations, spatial
      correlations, and invasion fronts are investigated. We find that spatial
      variability in the predation rate results in more localized activity patches,
      which in turn causes a remarkable increase in the asymptotic population densities
      of both predators and prey and accelerated front propagation.

PMID- 19113756
TI  - Slip and flow of hard-sphere colloidal glasses.
AB  - We study the flow of concentrated hard-sphere colloidal suspensions along smooth,
      nonstick walls using cone-plate rheometry and simultaneous confocal microscopy.
      In the glass regime, the global flow shows a transition from Herschel-Bulkley
      behavior at large shear rate to a characteristic Bingham slip response at small
      rates, absent for ergodic colloidal fluids. Imaging reveals both the "solid"
      microstructure during full slip and the local nature of the "slip to shear"
      transition. Both the local and global flow are described by a phenomenological
      model, and the associated Bingham slip parameters exhibit characteristic scaling
      with size and concentration of the hard spheres.

PMID- 19113757
TI  - Influence of boundary conditions on yielding in a soft glassy material.
AB  - The yielding behavior of a sheared Laponite suspension is investigated within a 1
      mm gap under two different boundary conditions. No-slip conditions, ensured by
      using rough walls, lead to shear localization as already reported in various soft
      glassy materials. When apparent wall slip is allowed using a smooth geometry, the
      sample breaks up into macroscopic solid pieces that get slowly eroded by the
      surrounding fluidized material up to the point where the whole sample is fluid.
      Such a drastic effect of boundary conditions on yielding suggests the existence
      of some macroscopic characteristic length that could be connected to
      cooperativity effects in jammed materials under shear.

PMID- 19113758
TI  - Bundle formation in polyelectrolyte brushes.
AB  - Bundle formation of the vertically oriented polyelectrolytes within
      polyelectrolyte brushes is studied with x-ray reflectivity and grazing-incidence
      diffraction as a function of grafting density and ion concentration. At 0.8 Molar
      monomer concentration and without added salt, a bundle consists of two chains and
      is 50 A long. On the addition of up to 1M CsCl, the aggregation number increases
      up to 15 whereas the bundle length approaches a limiting value, 20 A. We suggest
      that the bundle formation is determined by a balance between long-ranged
      electrostatic repulsion, whose range and amplitude is decreased on salt addition,
      and short-ranged attraction.

PMID- 19113759
TI  - Fixation and consensus times on a network: a unified approach.
AB  - We investigate a set of stochastic models of biodiversity, population genetics,
      language evolution, and opinion dynamics on a network within a common framework.
      Each node has a state 0<x(i)<1 with interactions specified by strengths m(ij).
      For any set of m(ij), we derive an approximate expression for the mean time to
      reach fixation or consensus (all x(i)=0 or 1). Remarkably, in a case relevant to
      language change, this time is independent of the network structure.

PMID- 19113760
TI  - Creation, manipulation, and detection of Abelian and non-Abelian anyons in
      optical lattices.
AB  - Anyons are particlelike excitations of strongly correlated phases of matter with
      fractional statistics, characterized by nontrivial changes in the wave function,
      generalizing Bose and Fermi statistics, when two of them are interchanged. This
      can be used to perform quantum computations [A. Yu. Kitaev, Ann. Phys. (N.Y.)
      303, 2 (2003)]. We show how to simulate the creation and manipulation of Abelian
      and non-Abelian anyons in topological lattice models using trapped atoms in
      optical lattices. Our proposal, feasible with present technology, requires an
      ancilla particle which can undergo single-particle gates, be moved close to each
      constituent of the lattice and undergo a simple quantum gate, and be detected.

PMID- 19113761
TI  - Multimode memories in atomic ensembles.
AB  - The ability to store multiple optical modes in a quantum memory allows for
      increased efficiency of quantum communication and computation. Here we compute
      the multimode capacity of a variety of quantum memory protocols based on light
      storage in ensembles of atoms. We find that adding a controlled inhomogeneous
      broadening improves this capacity significantly.

PMID- 19113762
TI  - Bell test for the free motion of material particles.
AB  - We present a scheme to establish nonclassical correlations in the motion of two
      macroscopically separated massive particles without resorting to entanglement in
      their internal degrees of freedom. It is based on the dissociation of a diatomic
      molecule with two temporally separated Feshbach pulses generating a motional
      state of two counterpropagating atoms that is capable of violating a Bell
      inequality by means of correlated single-particle interferometry. We evaluate the
      influence of dispersion on the Bell correlation, showing it to be important but
      manageable in a proposed experimental setup. The latter employs Bose-Einstein
      condensation of fermionic lithium atoms, uses laser-guided atom interferometry,
      and seems to be within the reach of present-day technology.

PMID- 19113763
TI  - Stochastic pumping of heat: approaching the Carnot efficiency.
AB  - Random noise can generate a unidirectional heat current across asymmetric nano
      objects in the absence (or against) a temperature gradient. We present a minimal
      model for a molecular-level stochastic heat pump that may operate arbitrarily
      close to the Carnot efficiency. The model consists a fluctuating molecular unit
      coupled to two solids characterized by distinct phonon spectral properties. Heat
      pumping persists for a broad range of system and bath parameters. Furthermore, by
      filtering the reservoirs' phonons the pump efficiency can approach the Carnot
      limit.

PMID- 19113764
TI  - Constraints on massive-graviton dark matter from pulsar timing and precision
      astrometry.
AB  - The effect of a narrow-band isotropic stochastic gravitational wave background on
      pulsar timing and astrometric measurements is studied. Such a background appears
      in some theories of gravity. We show that the existing millisecond pulsar timing
      accuracy (approximately 0.2 micros) strongly constrains possible observational
      consequences of theory of massive gravity with spontaneous Lorentz braking,
      essentially ruling out significant contribution of massive gravitons to the local
      dark halo density. The present-day accuracy of astrometrical measurements
      (approximately 100 microarc sec) sets less stringent constraints on this theory.

PMID- 19113765
TI  - Constraining Lorentz violation with cosmology.
AB  - The Einstein-aether theory provides a simple, dynamical mechanism for breaking
      Lorentz invariance. It does so within a generally covariant context and may
      emerge from quantum effects in more fundamental theories. The theory leads to a
      preferred frame and can have distinct experimental signatures. In this Letter, we
      perform a comprehensive study of the cosmological effects of the Einstein-aether
      theory and use observational data to constrain it. Allied to previously
      determined consistency and experimental constraints, we find that an Einstein
      aether universe can fit experimental data over a wide range of its parameter
      space, but requires a specific rescaling of the other cosmological densities.

PMID- 19113766
TI  - Hot solar-wind helium: direct evidence for local heating by Alfven-cyclotron
      dissipation.
AB  - A study of solar-wind hydrogen and helium temperature observations collected by
      the Wind spacecraft offers compelling evidence of heating by an Alfven-cyclotron
      dissipation mechanism. Observations are sorted by the rate of Coulomb
      interactions, or collisional age, in the plasma and the differential flow between
      the two species. We show that helium is preferentially heated perpendicular to
      the magnetic field direction by more than a factor of 6 when the flow between the
      species is small relative to the Alfven wave speed and collisions are infrequent.
      These signatures are consistent with predictions of dissipation in the presence
      of multiple ion species. We also report an unexpected result: observations of
      efficient heating of helium parallel to the magnetic field for large differential
      flow relative to the sound speed.

PMID- 19113767
TI  - Realization of Cohen-Glashow very special relativity on noncommutative space
      time.
AB  - We show that the Cohen-Glashow very special relativity (VSR) theory [A. G. Cohen
      and S. L. Glashow, Phys. Rev. Lett. 97, 021601 (2006)] can be realized as the
      part of the Poincare symmetry preserved on a noncommutative Moyal plane with
      lightlike noncommutativity. Moreover, we show that the three subgroups relevant
      to VSR can also be realized in the noncommutative space-time setting. For all of
      these three cases, the noncommutativity parameter theta(mu upsilon) should be
      lightlike (theta(mu upsilon) theta mu upsilon = 0). We discuss some physical
      implications of this realization of the Cohen-Glashow VSR.

PMID- 19113768
TI  - Limits on anomalous spin-spin couplings between neutrons.
AB  - We report experimental limits on new spin-dependent macroscopic forces between
      neutrons. We measured the nuclear Zeeman frequencies of a 3He/129Xe maser while
      modulating the nuclear spin polarization of a nearby 3He ensemble in a separate
      glass cell. We place limits on the coupling strength of neutron spin-spin
      interactions mediated by light pseudoscalar particles like the axion
      [g(p)g(p)/(4pihc)] at the 3 x 10(-7) level for interaction ranges longer than
      about 40 cm. This limit is about 10(-5) the size of the magnetic dipole-dipole
      interaction between neutrons.

PMID- 19113770
TI  - Coherent control of low loss surface polaritons.
AB  - We propose fast all-optical control of surface polaritons by placing an
      electromagnetically induced transparency (EIT) medium at an interface between two
      materials. EIT provides longitudinal compression and a slow group velocity, while
      matching properties of the two materials at the interface provides strong
      transverse confinement. In particular, we show that an EIT medium near the
      interface between a dielectric and a negative-index metamaterial can establish
      tight longitudinal and transverse confinement plus extreme slowing of surface
      polaritons, in both transverse electric and transverse magnetic polarizations,
      while simultaneously avoiding losses.

PMID- 19113771
TI  - Parametric normal-mode splitting in cavity optomechanics.
AB  - Recent experimental progress in cavity optomechanics has allowed cooling of
      mesoscopic mechanical oscillators via dynamic backaction provided by the
      parametric coupling to either an optical or an electrical resonator. Here we
      analyze the occurrence of normal-mode splitting in backaction cooling at high
      input power. We find that a hybridization of the oscillator's motion with the
      fluctuations of the driving field occurs and leads to a splitting of the
      mechanical and optical fluctuation spectra. Moreover, we find that cooling
      experiences a classical limitation through the cavity lifetime.

PMID- 19113772
TI  - Coupling nanomechanical cantilevers to dipolar molecules.
AB  - We investigate the coupling of a nanomechanical oscillator in the quantum regime
      with molecular (electric) dipoles. We find theoretically that the cantilever can
      produce single-mode squeezing of the center-of-mass motion of an isolated trapped
      molecule and two-mode squeezing of the phonons of an array of molecules. This
      work opens up the possibility of manipulating dipolar crystals, which have been
      recently proposed as quantum memory, and more generally, is indicative of the
      promise of nanoscale cantilevers for the quantum detection and control of atomic
      and molecular systems.

PMID- 19113773
TI  - Compactification of nonlinear patterns and waves.
AB  - We present a nonlinear mechanism(s) which may be an alternative to a missing wave
      speed: it induces patterns with a compact support and sharp fronts which
      propagate with a finite speed. Though such mechanism may emerge in a variety of
      physical contexts, its mathematical characterization is universal, very simple,
      and given via a sublinear substrate (site) force. Its utility is shown studying a
      Klein-Gordon -u(tt) + [phi/(u(x)]x = P'(u) equation, where phi'(sigma) = sigma +
      beta sigma3 and endowed with a subquadratic site potential P(u) approximately /1
      u2/(alpha+1), 0 < or = alpha < 1, and the Schrodinger iZt + inverted delta2 Z =
      G(/Z/)Z equation in a plane with G(A) = gammaA(-delta) - sigmaA2, 0 < delta < or
      = 1.

PMID- 19113774
TI  - Nonuniversality of the specific heat in glass forming systems.
AB  - We present new simulation results for the specific heat in a classical model of a
      binary mixture glass former in two dimensions. We show that in addition to the
      formerly observed specific heat peak, there is a second peak at lower
      temperatures which was not observable in earlier simulations. This is a surprise,
      as most texts on the glass transition expect a single specific heat peak. We
      explain the physics of the two specific heat peaks by the micromelting of two
      types of clusters. While this physics is easily accessible, the consequences are
      that one should not expect any universality in the temperature dependence of the
      specific heat in glass formers.

PMID- 19113775
TI  - Signature of low-dimensional diffusion in complex systems.
AB  - We present a clear signature of the dimensionality of water diffusion in a powder
      sample of a synthetic hectorite (a model clay), by analyzing the corresponding
      neutron scattering functions. The data follow the theoretical predictions for a
      powder-averaged two-dimensional diffusion, with a two-dimensional diffusion
      coefficient of 0.75 x 10(-9) m2 s(-1). Neutron scattering data of bulk water are
      used as a reference, representing motion in three dimensions. The approach is
      based on analyzing the scattered intensity at zero energy transfers, along with
      the broadening of the scattering functions, collected at a wide range of energy
      resolutions. The mathematical relationship between these two quantities follows,
      for a given shape of the resolution function, a universal master curve,
      independent of the diffusion coefficient, but strongly dependent on the
      dimensionality of the motion, which can thus be determined with clarity.

PMID- 19113776
TI  - One-dimensional defect-mediated diffusion of Si adatoms on the Si(111)-(5 x 2)-Au
      surface.
AB  - Using scanning tunneling microscopy, we determine that the one-dimensional
      diffusion of Si adatoms along the Si(111)-(5 x 2)-Au surface reconstruction
      occurs by a defect-mediated mechanism. Distinctive diffusion statistics,
      especially correlations between sequential adatom displacements, imply that the
      displacements are triggered by an interaction with a defect that is localized to
      the adatom. The defect is intrinsic and thermally activated. The measured
      diffusion statistics are modeled accurately by a Monte Carlo simulation. The
      measured adatom diffusion activation barrier is 1.24 +/- 0.08 eV.

PMID- 19113777
TI  - Characteristic length scale of nanorod diameter during growth.
AB  - This Letter proposes a characteristic length scale on surfaces and demonstrates
      its impact on nanorod growth. The proposed length scale is the dimension of a
      surface segment bounded by multiple-layer steps. Lattice kinetic Monte Carlo
      simulations, taking Cu as the prototype of nanorods, show that the proposed
      length scale (i) exists as the result of a diffusion barrier of adatoms down
      multiple-layer steps, (ii) dictates that the diameter of metallic nanorods is on
      the order of several hundred nanometers, and (iii) sets the upper limit of the
      facet dimension.

PMID- 19113778
TI  - Tuning the stoichiometry of surface oxide phases by step morphology: Ag(511)
      versus Ag(210).
AB  - We show by vibrational and photoemission spectroscopy and by ab initio
      calculations that in ultrahigh vacuum oxygen adsorption at stepped Ag surfaces
      causes the formation of surface oxide phases with different stoichiometry,
      depending on the morphology of the steps involved in the nucleation process. On
      Ag(511), characterized by close-packed steps and (100) terraces, subsurface O
      occupies tetrahedral interstitials and an Ag2O-like phase forms; on Ag(210),
      showing open step edges, subsurface oxygen ends up off center in octahedral sites
      and an AgO-like structure nucleates.

PMID- 19113779
TI  - All-electrical detection of the relative strength of Rashba and Dresselhaus spin
      orbit interaction in quantum wires.
AB  - We propose a method to determine the relative strength of Rashba and Dresselhaus
      spin-orbit interaction from transport measurements without the need of fitting
      parameters. To this end, we make use of the conductance anisotropy in narrow
      quantum wires with respect to the directions of an in-plane magnetic field, the
      quantum wire, and the crystal orientation. We support our proposal by numerical
      calculations of the conductance of quantum wires based on the Landauer formalism
      which show the applicability of the method to a wide range of parameters.

PMID- 19113780
TI  - Optical bistability in a GaAs-based polariton diode.
AB  - We report on a new type of optical nonlinearity in a polariton p-i-n microcavity.
      Abrupt switching between the strong and weak coupling regime is induced by
      controlling the electric field within the cavity. As a consequence, bistable
      cycles are observed for low optical powers (2-3 orders of magnitude less than for
      Kerr induced bistability). Signatures of switching fronts propagating through the
      whole 300 x 300 microm2 mesa surface are evidenced.

PMID- 19113769
TI  - Measurement of the branching fractions of B-->D**(l) nu(l) decays in events
      tagged by a fully reconstructed B meson.
AB  - We report a measurement of the branching fractions of B-->D**(l) nu(l), decays
      based on 417 fb(-1) of data collected at the Y(4S) resonance with the BABAR
      detector at the PEP-II e+e- storage rings. Events are selected by full
      reconstructing one of the B mesons in a hadronic decay mode. A fit to the
      invariant mass differences m(D(*) pi)- m(D(*)) is performed to extract the signal
      yields of the different D** states. We observe the B-->D**l(-1)nu(l) decay modes
      corresponding to the four D states predicted by heavy quark symmetry with a
      significance greater than 5 standard deviations including systematic
      uncertainties.

PMID- 19113781
TI  - Pi resonance of chemisorbed alkali atoms on noble metals.
AB  - We have performed a joint experimental and theoretical study of the unoccupied
      electronic structure of alkali adsorbates on the (111) surfaces of Cu and Ag.
      Combining angle- and time-resolved two-photon photoemission spectroscopy with
      wave packet propagation calculations we show that, along with the well known
      sigma resonance oriented along the surface normal, there exist long-lived alkali
      localized resonances oriented parallel to the surface (pi symmetry). These new
      resonances are stabilized by the projected band gap of the substrate and emerge
      primarily from the mixing of the p and d Rydberg orbitals of the free alkali atom
      modified by the interaction with the surface.

PMID- 19113782
TI  - Rashba-type spin-orbit splitting of quantum well states in ultrathin Pb films.
AB  - A Rashba-type spin-orbit splitting is found for quantum well states formed in
      ultrathin Pb films on Si (111). The resulting momentum splitting is comparable to
      what is found for semiconductor heterostructures. The splitting shows no coverage
      dependency and the sign of the spin polarization is reversed compared to Rashba
      splitting in the Au(111) surface state. We explain our results by competing
      effects at the two boundaries of the Pb layer.

PMID- 19113783
TI  - Evidence for strong itinerant spin fluctuations in the normal state of
      CeFeAsO0.89F0.11 iron-oxypnictide superconductors.
AB  - The electronic structure in the normal state of CeFeAsO0.89F0.11 oxypnictide
      superconductors has been investigated with x-ray absorption and photoemission
      spectroscopy. All of the data exhibit signatures of Fe d-electron itinerancy.
      Exchange multiplets appearing in the Fe 3s core level indicate the presence of
      itinerant spin fluctuations. These findings suggest that the underlying physics
      and the origin of superconductivity in these materials are likely to be quite
      different from those of the cuprate high-temperature superconductors. These
      materials provide opportunities for elucidating the role of magnetic fluctuations
      in high-temperature superconductivity.

PMID- 19113784
TI  - Evidence for a magnetic proximity effect up to room temperature at Fe/(Ga, Mn)As
      interfaces.
AB  - We report x-ray magnetic circular dichroism and superconducting quantum
      interference device magnetometry experiments to study magnetic order and coupling
      in thin Fe/(Ga, Mn)As(100) films. We observe induced magnetic order in the (Ga,
      Mn)As layer that extends over more than 2 nm, even at room temperature. We find
      spectroscopic evidences of a hybridized d configuration of Mn atoms in Fe/(Ga,
      Mn)As, with negligible Mn diffusion and/or MnFe intermixing. We show by
      experiment as well as by theory that the magnetic moment of the Mn ions couples
      antiparallel to the moment of the Fe overlayer.

PMID- 19113785
TI  - Antiferromagnetic order with atomic layer resolution in EuTe(111) films.
AB  - The temperature dependences of the magnetizations of individual atomic layers
      across an epitaxial antiferromagnetic EuTe film were derived from virtually
      background-free magnetic Bragg peaks with pronounced Laue oscillations recorded
      with soft x rays at the Eu-M5 resonance. The magnetizations of the outermost
      layers decrease significantly differently from those of bulk layers, in agreement
      with Heisenberg-Monte Carlo calculations. The results demonstrate the
      applicability of the method to complex ordering phenomena at surfaces and
      interfaces of thin films.

PMID- 19113786
TI  - From scattering parameters to Snell's law: a subwavelength near-infrared negative
      index metamaterial.
AB  - A general relation is derived between the band structure of an arbitrary low-loss
      unit cell and its effective index of refraction. In addition, we determine the
      maximum unit cell size that defines the "metamaterial regime" [D. R. Smith et
      al., Phys. Rev. E 71, 036617 (2005)]. Furthermore, these general rules allow for
      the design of a subwavelength near-infrared negative-index material, where the
      negative refractive index is verified by band calculations to be a bulk property.
      Full-wavelength simulations of prisms consisting of these unit cells suggest
      behavior consistent with Snell's law in the negative-index regime.

PMID- 19113787
TI  - Diamagnetic response of exciton complexes in semiconductor quantum dots.
AB  - We report measurements of diamagnetic shifts for different exciton complexes
      confined in small InAs quantum dots. The measured diamagnetic responses are
      sensitive to the number of carriers in the exciton complexes, with systematic
      differences between neutral excitons, biexcitons, and trions. Theoretical
      calculations suggest that such systematic differences arise from very different
      extents of electron and hole wave functions confined in small quantum dots. The
      measured magnetic response of Coulomb energies is found to vary with the cube of
      the wave function extent, and can be a sensitive probe to the electron-hole wave
      function asymmetry.

PMID- 19113788
TI  - Alternative view of dynamic arrest in colloid-polymer mixtures.
AB  - Colloid-polymer mixtures are frequently viewed as an effective one-component
      fluid (the colloid) with polymer-mediated depletion interactions. This view,
      together with conventional mode coupling theory, constitutes the current
      description of the reentrant glass transition experimentally observed in these
      systems. A more fundamental view is to consider these systems as what they
      actually are, namely, genuine highly size-asymmetric binary colloidal mixtures.
      In this Letter we demonstrate that the recently developed multicomponent self
      consistent generalized Langevin equation theory of dynamic arrest correctly
      predicts the observed reentrance in excellent quantitative agreement with the
      experimental glass transition line of a colloid-polymer mixture. In this scenario
      the polymer plays a much more active dynamic role than in the conventional one
      component description.

PMID- 19113789
TI  - Enhanced diffusion and ordering of self-propelled rods.
AB  - Starting from a minimal physical model of self-propelled hard rods on a substrate
      in two dimensions, we derive a modified Smoluchowski equation for the system.
      Self-propulsion enhances longitudinal diffusion and modifies the mean-field
      excluded volume interaction. From the Smoluchowski equation we obtain
      hydrodynamic equations for rod concentration, polarization and nematic order
      parameter. New results at large scales are a lowering of the density of the
      isotropic-nematic transition and a strong enhancement of boundary effects in
      confined self-propelled systems.

PMID- 19113791
TI  - Where does high-quality research in economic evaluation come from?

PMID- 19113792
TI  - Nighttime blood pressure is the blood pressure.

PMID- 19113793
TI  - Pharmacokinetics of mycophenolic acid in patients with lupus nephritis.
AB  - STUDY OBJECTIVES: To evaluate and describe the pharmacokinetics of mycophenolic
      acid and its metabolite, mycophenolic acid glucuronide (MPAG), in patients with
      lupus nephritis, and to determine the effects of clinical parameters (urinary
      protein excretion as measured by the urinary protein:creatinine ratio, serum
      albumin level, and creatinine clearance) and demographic variables (age, race,
      sex) on the pharmacokinetics of total and unbound mycophenolic acid and MPAG.
      DESIGN: Pharmacokinetic analysis. SETTING: University-affiliated general clinical
      research center. PATIENTS: Eighteen patients with biopsy-confirmed lupus
      nephritis who were receiving maintenance therapy with mycophenolic acid for at
      least 2 weeks. INTERVENTION: Plasma and urine samples were collected for 24 hours
      and were assayed by high-performance liquid chromatography with ultraviolet
      detection. MEASUREMENTS AND MAIN RESULTS: Time to maximum concentration was
      variable (0.5-8 hrs). Mean +/- SD fraction of unbound mycophenolic acid was 2.6
      +/- 1.9%, and oral clearance (Cl/F) was about 2-fold higher (343 +/- 200 ml/min)
      than previously reported. Multiple regression analysis showed that Cl/F of
      mycophenolic acid was predicted by creatinine clearance and serum albumin level:
      ln Cl/F = 5.358 + 0.0092 (creatinine clearance) - 0.078 (ranked albumin),
      R(2)=51.1%, p=0.0195. Patients with urinary protein excretion of 1 g/day or
      higher had lower minimum (trough) concentrations and area under the concentration
      time curve (AUC(0-12)) profiles and higher Cl/F values compared with patients
      with urinary protein excretion of less than 1 g/day. Patients with serum albumin
      levels less than 4 g/dl had higher mycophenolic acid unbound clearance and MPAG
      renal clearance from 0-12 hours versus those with serum albumin levels of 4 g/dl
      or greater. Recycling AUC (AUC(6-12)), as well as sex and age (both equally),
      predicted renal clearance of MPAG. CONCLUSION: Both creatinine clearance and
      serum albumin level were identified as primary contributors to mycophenolic acid
      exposure and should be considered when evaluating dosages. The results of future
      studies should clarify the interactions of other variables on drug exposure and
      treatment responses. Clinicians need to be mindful of clinical changes that occur
      throughout the course of lupus nephritis in order to maintain efficacy and reduce
      toxicity from mycophenolic acid therapy.

PMID- 19113794
TI  - Pharmacology and antifungal properties of anidulafungin, a new echinocandin.
AB  - Anidulafungin is the third echinocandin antifungal agent to receive approval from
      the United States Food and Drug Administration. It is indicated for the treatment
      of esophageal candidiasis, candidemia, and other candidal infections.
      Anidulafungin is fungicidal against Candida species, including Candida glabrata
      and isolates resistant to azoles and polyenes. The drug's efficacy is comparable
      to that of fluconazole for the treatment of esophageal candidiasis, and it is
      effective in patients with invasive candidiasis and candidemia. Anidulafungin is
      distinct among the echinocandins in that it undergoes slow, nonenzymatic chemical
      degradation. As a consequence, impairments in renal or hepatic function do not
      substantially alter its pharmacokinetics. In addition, anidulafungin has not
      demonstrated any drug-drug interactions because it is not a substrate, inhibitor,
      or inducer of the cytochrome P450 enzyme system. Anidulafungin is well tolerated
      in adults and pediatric patients, with few reported adverse drug events. The
      safety, tolerability, and potent fungicidal activity of anidulafungin against
      Candida species make it a reasonable alternative in the treatment of patients
      with serious candidal infections.

PMID- 19113795
TI  - Role of angiotensin-converting enzyme inhibitors, angiotensin II receptor
      blockers, and aldosterone antagonists in the prevention of atrial and ventricular
      arrhythmias.
AB  - Atrial arrhythmias, ventricular arrhythmias, and sudden cardiac death (SCD) are
      significant health problems and an economic burden to society. The renin
      angiotensin-aldosterone system (RAAS) may play a key role in the occurrence of
      structural and electrical remodeling, potentially explaining the development of
      atrial and ventricular arrhythmias. Angiotensin II has been shown to regulate
      cardiac cell proliferation and to modulate cardiac myocyte ion channels. Results
      of post hoc analyses from prospective clinical trials appear to show that
      angiotensin-converting enzyme (ACE) inhibitors and angiotensin II receptor
      blockers (ARBs) are most effective in the prevention of new-onset atrial
      fibrillation in patients with heart failure. It is difficult to determine if
      these agents are useful in the prevention of new-onset atrial fibrillation after
      myocardial infarction, and available evidence suggests that the benefit of ACE
      inhibitors and ARBs for prevention of new-onset atrial fibrillation in patients
      with hypertension appears limited to those with left ventricular hypertrophy.
      Patients with structural changes in cardiac muscle, such as those with heart
      failure and left ventricular hypertrophy, appear to benefit the most from RAAS
      blockade, possibly due to the theory of reversal of cardiac remodeling. There is
      no evidence, to our knowledge, that either ACE inhibitors or ARBs facilitate
      direct electrical current cardioversion in patients with atrial fibrillation;
      however, it appears that RAAS blockade may be useful in the prevention of
      recurrent atrial fibrillation after direct electrical current cardioversion.
      Whether ACE inhibitors may prevent life-threatening ventricular arrhythmias or
      SCD is unclear. Aldosterone antagonists appear to be useful for the prevention of
      SCD in patients with left ventricular systolic dysfunction. Results from ongoing
      clinical trials are anticipated to provide further insight on the potential roles
      of RAAS inhibitors for the prevention of cardiac arrhythmias.

PMID- 19113796
TI  - Depression in patients with heart failure: clinical implications and management.
AB  - Mortality and morbidity rates remain high in patients with heart failure despite
      advances in medical therapy. Heart failure can also significantly worsen quality
      of life. Attention has been paid to evaluating the effects of psychological
      disease in patients with heart failure. Depression rates are higher in patients
      with heart failure than in the general population. Depression has been associated
      with worse outcomes in patients with heart failure. Those at highest risk for
      depression include patients with implantable cardioverter-defibrillators, alcohol
      abuse, history of depression, and multiple comorbidities. Depression may be
      underdiagnosed in the heart failure population, as symptoms can often be similar
      in the two disease states. Evidence is limited on the effects of pharmacologic
      and nonpharmacologic therapy for depression, specifically in patients with heart
      failure. Based on the available literature, patients with heart failure should be
      screened routinely for depression. Treatment is known to improve quality of life,
      but its effect on outcomes such as mortality and hospital admissions for heart
      failure remains unknown. If treatment includes pharmacologic strategies,
      selective serotonin reuptake inhibitors (especially paroxetine and sertraline),
      mirtazapine, and nefazodone have the strongest efficacy evidence in this
      population. Based on safety data of these agents and after consideration of
      comorbid conditions and the potential for drug interactions, a selective
      serotonin reuptake inhibitor should be used as first-line therapy. Finally,
      clinicians should not avoid beta-blockers in those with a diagnosis of
      depression, as recent evidence demonstrates that these agents are not associated
      with inducing or worsening depressive symptoms.

PMID- 19113797
TI  - Antipsychotic-induced hyperprolactinemia.
AB  - Use of antipsychotic agents has been associated with hyperprolactinemia, or
      elevated prolactin levels; this hormonal abnormality can interfere with the
      functioning of reproductive, endocrine, and metabolic systems. As antipsychotic
      agents are increasingly used for both United States Food and Drug Administration
      approved and nonapproved indications, many individuals are at risk for developing
      antipsychotic-induced hyperprolactinemia. First-generation antipsychotics pose
      the greatest risk of causing this adverse effect; however, second-generation
      antipsychotics, particularly risperidone and paliperidone, also often increase
      prolactin secretion. Hyperprolactinemia has short- and long-term consequences
      that can seriously affect quality of life: menstrual disturbances, galactorrhea,
      sexual dysfunction, gynecomastia, infertility, decreased bone mineral density,
      and breast cancer. Although many of these are definitively connected to elevated
      prolactin levels, some, such as breast cancer, require further study. Both
      clinicians and patients should be aware of hyperprolactinemia-associated effects.
      To prevent or alleviate the condition, tailoring an antipsychotic drug regimen to
      each individual patient is essential. In addition, the risk of hyperprolactinemia
      can be minimized by using the lowest effective dose of the antipsychotic agent.
      If the effects of prolactin are evident, the drug can be changed to another agent
      that is less likely to affect prolactin levels; alternatively, a dopamine agonist
      may be added, although this may compromise antipsychotic efficacy. Additional
      research is needed to clarify the appropriate level of monitoring, the long-term
      effects, and the optimal treatment of antipsychotic-induced hyperprolactinemia.

PMID- 19113798
TI  - Use of gabapentin in patients experiencing hot flashes.
AB  - Hot flashes occur frequently in menopausal women and in women with breast cancer,
      diminishing their quality of life. A report from the Women's Health Initiative
      published in 2002 raised concerns about the long-term safety of estrogen therapy.
      As a result, nonhormonal alternatives have emerged as preferred treatments.
      Gabapentin is an anticonvulsant that the United States Food and Drug
      Administration approved as an adjunct therapy for partial seizures and
      postherpetic neuralgia. Somnolence, dizziness, ataxia, fatigue, nystagmus, and
      peripheral edema are adverse effects commonly associated with gabapentin in the
      treatment of epilepsy and postherpetic neuralgia. The North American Menopause
      Society and the American College of Obstetricians and Gynecologists recommend the
      use of gabapentin as an option for managing hot flashes in women who are
      unwilling to take estrogen-containing supplements. To evaluate the efficacy and
      safety of gabapentin for the treatment of hot flashes in women with menopause
      and/or breast cancer, we performed a search of the MEDLINE database (1966-March
      2008) and International Pharmaceutical Abstracts, as well as manually searching
      reference articles for relevant articles and abstracts; 10 clinical studies were
      identified. Although the studies were few, all showed gabapentin to be safe and
      effective in the treatment of hot flashes. At doses used to control hot flashes,
      gabapentin was well tolerated, with drowsiness as its most reported adverse
      effect. Gabapentin can be considered effective in the treatment of hot flashes
      and should be considered a reasonable alternative when estrogen therapy is not
      desired.

PMID- 19113799
TI  - High-impact articles related to the management of heart failure: 2008 update.
AB  - This compilation is part of a series of articles identifying important literature
      in cardiovascular pharmacotherapy. This bibliography focuses on
      pharmacotherapeutic management of acute decompensated and chronic heart failure
      and provides an update of the heart failure bibliography published in
      Pharmacotherapy in 2004. Most of the cited works present the results of landmark
      clinical studies that have shaped the management of patients with heart failure.
      Limited primary literature is available for some topics, thus pertinent review
      articles are also listed. In addition, consensus documents formed by expert
      panels are reviewed. This compilation may serve as a teaching tool, reference
      resource, or update of the literature for pharmacy clinicians, physicians, and
      students.

PMID- 19113800
TI  - Falsely low hemoglobin A1c levels in a patient receiving ribavirin and
      peginterferon alfa-2b for hepatitis C.
AB  - The effect of treatment for hepatitis C viral infection on hemoglobin A(1c) (A1C)
      levels is not well described in the literature. We describe a 59-year-old man
      with type 2 diabetes mellitus whose A1C level became falsely low when ribavirin
      and peginterferon alfa-2b therapy were started for treatment of hepatitis C.
      After treatment was discontinued, the patient's A1C returned to its previous
      baseline value. Use of the Naranjo adverse drug reaction probability scale
      indicated a probable relationship (score of 7) between the patient's low AIC
      level and his ribavirin-peginterferon alfa-2b therapy. Clinicians should be aware
      that combination therapy for hepatitis C may affect A1C values. To maintain
      accurate glucose control in patients with diabetes who are receiving treatment
      for hepatitis C, it is important that they self-monitor their blood glucose
      levels in conjunction with A1C data, especially when A1C values become falsely
      low.

PMID- 19113801
TI  - ACCP position statement: Clinical faculty development.

PMID- 19113802
TI  - ACCP white paper: Essential components of a faculty development program for
      pharmacy practice faculty.
AB  - Prospective, ongoing faculty development programs are important in the initial
      orientation and short- and long-term development of faculty in higher education.
      Pharmacy practice faculty are likely to benefit from a comprehensive faculty
      development program due to the complex nature of their positions, incomplete
      training in select areas, and multiple demands on their time. The need for
      faculty development programs is supported by the increased need for pharmacy
      practice faculty due to the increased number of colleges and schools of pharmacy,
      expanding enrollment in existing colleges and schools, and loss of existing
      senior faculty to retirement or other opportunities within or outside the
      academy. This White Paper describes a comprehensive faculty development program
      that is designed to enhance the satisfaction, retention, and productivity of new
      and existing pharmacy practice faculty. A comprehensive faculty development
      program will facilitate growth throughout a faculty member's career in pertinent
      areas. The structure of such a program includes an orientation program to provide
      an overview of responsibilities and abilities, a mentoring program to provide one
      on-one guidance from a mentor, and a sustained faculty development program to
      provide targeted development based on individual and career needs. The content
      areas to be covered in each component include the institution (e.g., culture,
      structure, roles, responsibilities), student-related activities, teaching
      abilities, scholarship and research abilities, practice abilities and the
      practice site, and professional abilities (e.g., leadership, career planning,
      balancing responsibilities). A general framework for a comprehensive pharmacy
      practice faculty development program is provided to guide each college, school,
      department, and division in the design and delivery of a program that meets the
      needs and desires of the institution and its faculty.

PMID- 19113803
TI  - ACCP: economic evaluations of clinical pharmacy services: 2001-2005.
AB  - The objectives of this review were to summarize and evaluate studies that
      measured the economic impact of clinical pharmacy services published between 2001
      and 2005 (inclusive) and to provide guidance on methodologic considerations to
      individuals performing such research in the future. A systematic literature
      search using the MEDLINE and International Pharmaceutical Abstracts databases was
      conducted to identify published economic evaluations of clinical pharmacy
      services. Studies were screened and then randomly assigned to reviewers, who
      reassessed inclusion and exclusion criteria and abstracted prespecified data from
      each study. Among the many characteristics examined in each study were study
      design and type of economic evaluation, setting and type of clinical pharmacy
      service, study quality, and results. Ninety-three articles were included in the
      final analysis. These studies were published in 43 different journals, most of
      which (68 [73.1%]) were pharmacy-based. Most studies were performed in hospitals
      (40 [43.0%]), ambulatory care clinics or physician's offices (20 [21.5%]), or
      community pharmacies (16 [17.2%]). The most common types of clinical pharmacy
      services evaluated were general pharmacotherapeutic monitoring services (32
      [34.4%]), target drug programs (27 [29%]), and disease state-management services
      (21 [22.6%]). Full economic evaluations were performed in just less than half (45
      [48.4%]) of the studies, and a positive economic benefit associated with clinical
      pharmacy services was noted in 31 (69%) of the 45 studies. Among 15 studies
      reporting data necessary to determine a benefit:cost ratio, the pooled median
      value was 4.81:1-meaning that for every $1 invested in clinical pharmacy
      services, $4.81 was achieved in reduced costs or other economic benefits. The
      quality of studies varied widely, with less than one half considered to be good
      to fair (40 [43.0%]); however, the proportion of studies using appropriate study
      designs increased compared with previous reviews. Based on the evidence examined
      in this review, clinical pharmacy services continue to provide a significant
      return on investment, but improvements are still needed in the methods used to
      evaluate the economic impact of these services.

PMID- 19113805
TI  - Photoregulation of ion permeation through a polyelectrolyte multilayer membrane
      by manipulating the chromophore orientation.
AB  - Toward the realization of nanoscale device control, we report a novel method for
      photoregulation of ion flux through a polyelectrolyte multilayer membrane by
      chromophore orientation that is adjusted either by illumination at normal
      incidence or by slantwise irradiation at an angle of 10 degrees with respect to
      the surface. Our results indicate that the chromophore reorientation caused by
      the slantwise irradiation controls the effective pore size and, consequently, the
      transport behavior on the nanoscale. The slantwise illumination, which includes
      six EZE photoisomerization cycles generated by alternately irradiating with
      ultraviolet (lambda = 360 nm) and visible (lambda = 450 nm) light, reversibly
      switches the orientation of E-azobenzene in the membrane between 53 +/- 2 degrees
      (high tilt) and 17 +/- 5 degrees (low tilt) with respect to the surface. The
      novel feature of this light-gated valve system is its extremely long-lived open
      switch state; this behavior stands in contrast to that of other systems based on
      labile photoisomers, which tend to instantly return to the thermodynamically
      stable state.

PMID- 19113806
TI  - In situ and ex situ SAXS investigation of colloidal sedimentation onto laterally
      patterned support.
AB  - We report on in situ investigations of colloidal ordering during gravity
      sedimentation from a colloidal suspension onto a prepatterned support using a
      polymeric surface relief grating (SRG) as the support. The ordering of colloids
      with a diameter of 420 nm was investigated by means of grazing-incidence small
      angle X-ray scattering (GISAXS) and transmission SAXS using a preparation cell
      guaranteeing stable temperature and humidity. GISAXS was used for in situ
      monitoring of the time evolution of colloidal ordering within the whole
      illuminated sample area. The onset of ordering was indicated by the increase of
      integrated intensity within a small time frame shortly before complete
      evaporation of the dispersant. Single domains of coated samples were investigated
      ex situ by SAXS in transmission geometry where the irradiated sample area was 200
      x 200 microm(2) only. Domains with the typical size of a few millimeters were
      observed varying in orientation and crystallographic structure for various
      positions at the sample. They were mainly oriented along the grooves of the
      grating, confirming the influence of the underlying grating on colloidal
      ordering.

PMID- 19113808
TI  - Phototocatalytic lithography of poly(propylene sulfide) block copolymers: toward
      high-throughput nanolithography for biomolecular arraying applications.
AB  - Photocatalytic lithography (PCL) is an inexpensive, fast, and robust method of
      oxidizing surface chemical moieties to produce patterned substrates. This
      technique has utility in basic biological research as well as various biochip
      applications. We report on porphyrin-based PCL for patterning poly(propylene
      sulfide) block copolymer films on gold substrates on the micrometer and
      submicrometer scales. We confirm chemical patterning with imaging ToF-SIMS and
      low-voltage SEM. Biomolecular patterning on micrometer and submicrometer scales
      is demonstrated with proteins, protein-linked beads. and fluorescently labeled
      proteins.

PMID- 19113809
TI  - AFM studies of the effect of temperature and electric field on the structure of a
      DMPC-cholesterol bilayer supported on a Au(111) electrode surface.
AB  - Atomic force microscopy (AFM) was used to characterize a phospholipid bilayer
      composed of 70 mol % 1,2-dimyristoyl-sn-glycero-3-phosphocholine (DMPC) and 30
      mol % cholesterol, at a Au(111) electrode surface. Results indicate that addition
      of cholesterol relaxes membrane elastic stress, increases membrane thickness, and
      reduces defect density. The thickness and thermotropic properties of the mixed
      DMPC-cholesterol bilayer supported at the gold electrode surface are quite
      similar to the properties of the mixed membrane in unilamellar vesicles. The
      stability of the supported membrane at potentials negative to the potential of
      zero charge E(pzc) was investigated. This study demonstrates that the bilayer
      supported at the gold electrode surface is stable provided the applied potential
      (E - E(pzc)) is less than -0.3 V. At larger polarizations, swelling of the
      membrane is observed. Polarizations larger than -1 V cause electrodewetting of
      the bilayer from the gold surface. At these negative potentials, the bilayer
      remains in close proximity to the metal surface, separated from it by a
      approximately 2 nm thick layer of electrolyte.

PMID- 19113810
TI  - Biocatalysis in water-in-ionic liquid microemulsions: a case study with
      horseradish peroxidase.
AB  - In this article we report the first results on the enzymatic activity of
      horseradish peroxidase (HRP) microencapsulated in water-in-ionic liquid (w/IL)
      microemulsions using pyrogallol as the substrate. Toward this goal, the system
      used in this study was composed of anionic surfactant AOT (sodium bis(2-ethyl-1
      hexyl)sulfosuccinate)/hydrophobic IL [C(8)mim][Tf(2)N] (1-octyl-3-methyl
      imidazolium bis(trifluoromethylsulfonyl)amide)/water/1-hexanol. In this system,
      the catalytic activity of HRP was measured as a function of substrate
      concentrations, W(0) (molar ratio of water to surfactant), pH, and 1-hexanol
      content. The curve of the activity-W(0) profile was found to be hyperbolic for
      the new microemulsion. The apparent Michaelis-Menten kinetic parameters (k(cat)
      and K(m)) were estimated and compared to those obtained from a conventional
      microemulsion. Apparently, it was found that HRP-catalyzed oxidation of
      pyrogallol by hydrogen peroxide in IL microemulsuions is much more effective than
      in a conventional AOT/water/isooctane microemulsion. The stability of HRP
      solubilized in the newly developed w/IL microemulsions was examined, and it was
      found that HRP retained almost 70% of its initial activity after incubation at 28
      degrees C for 30 h.

PMID- 19113811
TI  - Grand canonical Monte Carlo simulations of acetonitrile filling of silica pores
      of varying hydrophilicity/hydrophobicity.
AB  - Grand canonical Monte Carlo simulations have been used to determine the
      equilibrium density of acetonitrile in model amorphous silica pores with varying
      radius and surface chemistry. Pores of diameter approximately 2-4 nm were
      considered with different ratios of surface -OH moieties to -OC(CH(3))(3) groups.
      The calculations found that the acetonitrile density in the interior of all the
      pores is essentially identical with that of the bulk liquid. On the other hand, a
      slightly elevated liquid density is observed near the pore surface for pores with
      only -OH surface moieties. Replacement of surface -OH groups with -OC(CH(3))(3)
      units lengthens the liquid/pore interfacial region as acetonitrile molecules can
      insert themselves between the -OC(CH(3))(3) units. The results indicate that the
      major effect of changing the surface functionality comes from the differences in
      excluded volume rather than hydrogen-bonding effects. Finally, the choice of the
      acetonitrile potential can qualitatively change the results.

PMID- 19113812
TI  - Control of arrangement for s-triazine group in comb copolymers by the Langmuir
      Blodgett method and its structural estimation by NEXAFS spectroscopy.
AB  - We investigated the molecular orientation of organized molecular films with
      regard to solid-state structures for newly synthesized comb copolymers with 2
      vinyl-4,6-diamino-1,3,5-triazine (VDAT) by surface pressure-area (pi-A)
      isotherms, in-plane and out-of-plane X-ray diffraction (XRD), atomic force
      microscopy (AFM), and polarized near-edge X-ray absorption fine structure
      (NEXAFS) spectroscopy. Since VDAT has adsorption ability to an adenine-thymine
      base pair of a DNA molecule, control of orientation for VDAT units in monolayers
      is possible to form surface patterning of biomolecules and construct candidates
      of new biochip materials. In the bulk state, hydrogenated and fluorinated comb
      copolymers containing VDAT form side-chain crystals for a two-dimensional lattice
      spacing of 4.2 and 5.0 A, respectively. From the results of the differential
      scanning calorimetric (DSC) measurements, sharp-shaped melting peaks appear on
      the relatively lower temperature side of the thermograms. This result supports
      the formation of side-chain crystals in the synthesized comb copolymers. These
      monolayers of copolymers on the water surface were extremely condensed, except
      for the VDAT:OA = 5:1 copolymer. From the in-plane XRD measurement of multilayers
      on solids, changes in the two-dimensional lattice structure of fluorinated comb
      copolymer films containing VDAT units, as opposed to their bulk state, were
      confirmed. It seems that these structural changes are caused by the stronger pi
      pi interaction between the s-triazine rings rather than the van der Waals
      interaction between fluorocarbons. Polarized NEXAFS spectroscopy showed highly
      ordered orientation of s-triazine groups in the films based on the incident angle
      dependency of C and N1s-pi*(CN) transitions with synchrotron radiation. These
      experimental findings relate to well-ordered arrangement of functional groups
      supporting the side-chain rearrangement caused by the pi-pi interaction between
      the s-triazine rings.

PMID- 19113814
TI  - Covalent attachment of bent-core mesogens to silicon surfaces.
AB  - Two vinyl-terminated bent core-shaped liquid crystalline molecules that exhibit
      thermotropic antiferroelectric SmCPA phases have been covalently attached onto a
      hydrogen-terminated silicon(111) surface. The surface attachment was achieved via
      a mild procedure from a mesitylene solution, using visible light at room
      temperature. AFM measurements indicate that a smooth monolayer has been formed.
      The thickness of the monolayer was evaluated with ellipsometry and X-ray
      reflectivity. Although the molecules differ in length by four carbon atoms, the
      thickness of the resulting monolayers was the same. The measured thicknesses
      correspond quite well with the smectic layer thickness in the bulk liquid
      crystalline material, suggesting a similar self-organization within the
      monolayer. From attenuated total reflectance infrared (ATR-IR), which clearly
      shows the C-H and C-O vibrations, a tilt angle of the mesogens is deduced that
      also corresponds well with the tilt angle in the liquid crystalline state. X-ray
      photoelectron spectroscopy (XPS) measurements confirm the high quality of the
      monolayers, with only marginal silicon oxide formation. The elemental composition
      and amounts of different O and C atoms deduced from the high-resolution XPS
      correspond very well with the calculated compositions.

PMID- 19113815
TI  - Direct dehydrative N-pyridinylation of amides.
AB  - Electrophilic activation of secondary amides with trifluoromethanesulfonic
      anhydride in the presence of 2-fluoropyridine followed by introduction of a
      pyridine N-oxide derivative and warming affords the corresponding N-pyridinyl
      tertiary amide derivatives. A mechanism supported by in situ monitoring and
      deuterium labeling experiments is discussed.

PMID- 19113816
TI  - Benzofurans as efficient dienophiles in normal electron demand [4 + 2]
      cycloadditions.
AB  - Dearomatization of electron-poor benzofurans is possible through involvement of
      the aromatic 2,3-carbon-carbon double bond as dienophile in normal electron
      demand [4 + 2] cycloadditions. The tricyclic heterocycles thereby produced bear a
      quaternary center at the cis ring junction, a feature of many alkaloids such as
      morphine, galanthamine, or lunaridine. The products arising from the reaction
      have been shown to depend on different factors among which the type of the
      electron-withdrawing substituent of the benzofuran, the nature of the reacting
      diene, and the method of activation. In the presence of all-carbon dienes, the
      reaction yields the expected Diels-Alder adducts. When thermal activation is
      insufficient, a biactivation associating zinc chloride catalysis and high
      pressure is required to generate the cycloadducts in good yields and high
      stereoselectivities, for instance, when cyclohexadiene is involved in the
      process. The use of more functionalized dienes, such as those bearing alkoxy or
      silyloxy substituents, also shows the limits of the thermal activation, and
      hyperbaric conditions are, in this case, well-suited. The involvement of
      Danishefsky's diene induces a competition in the site of reactivity. The aromatic
      2,3-carbon-carbon double bond is unambiguously the most reactive dienophile, and
      the 3-carbonyl unit becomes a competitive site of reactivity with benzofurans
      bearing substituents prone to heterocyloaddition, in particular under Lewis acid
      activation. The sequential involvement of both the aromatic double bond and the
      carbonyl moiety as dienophiles is then possible by using an excess of diene under
      high-pressure activation. In line with the experimental results, DFT computations
      suggest that the Diels-Alder process involving the aromatic double bond is
      preferred over the hetero-Diels-Alder route through an asynchronous concerted
      transition state. However, Lewis acid catalysis appears to favor the
      heterocycloaddition pathway through a stepwise mechanism in some cases.

PMID- 19113818
TI  - In situ scanning tunneling microscopy on the dynamic process of the replacement
      of coronene on au (111) by 6-mercapto-1-hexanol.
AB  - The replacement of coronene monolayer on Au (111) by 6-mercapto-1-hexanol (MHO)
      was studied by in situ scanning tunneling microscopy (STM) in solutions. It was
      found that the rate of replacement depends strongly on the concentration of MHO.
      The replacement finished within a second at a higher concentration of MHO. At a
      lower concentration, the slow replacement could be followed by in situ STM. The
      replacement occurred initially near the elbow position of reconstructed Au (111)
      with the formation of pits in a single or several missing molecules. With the
      proceeding of replacement, these small pits expanded, and the surrounding
      coronene molecules were gradually substituted by MHO, which developed into
      ordered domains within a spatial confined environment. Meanwhile, the
      reconstruction of Au (111) was lifted. The replacement expanded fast along the
      reconstruction lines in the domain. For the fast replacement, a ( radical3 x
      radical3) R30 degrees adlattice was observed, while a c(4 x 2) superlattice was
      observed for the slow replacement. The close-packed phase of MHO self-assembled
      monolayers (SAMs) appeared directly instead of a flat-lying phase, which implied
      that the coronene molecules resist the direct contact of hydrocarbon chain of MHO
      with Au (111) surface. The replacing rate of the overall process exhibited a
      signoidal shape with time.

PMID- 19113817
TI  - Endosomal Nox2 facilitates redox-dependent induction of NF-kappaB by TNF-alpha.
AB  - Growing evidence suggests that NADPH oxidase (Nox)-derived reactive oxygen
      species (ROS) play important roles in regulating cytokine signaling. We have
      explored how TNF-alpha induction of Nox-dependent ROS influences NF-kappaB
      activation. Cellular stimulation by TNF-alpha induced NADPH-dependent superoxide
      production in the endosomal compartment, and this ROS was required for IKK
      mediated activation of NF-kappaB. Inhibiting endocytosis reduced the ability of
      TNF-alpha to induce both NADPH-dependent endosomal superoxide and NF-kappaB,
      supporting the notion that redox-dependent signaling of the receptor occurs in
      the endosome. Molecular analyses demonstrated that endosomal H(2)O(2) was
      critical for the recruitment of TRAF2 to the TNFR1/TRADD complex after
      endocytosis. Studies using both Nox2 siRNA and Nox2-knockout primary fibroblasts
      indicated that Nox2 was critical for TNF-alpha-mediated induction of endosomal
      superoxide. Redox-active endosomes that form after TNF-alpha or IL-1 beta
      induction recruit several common proteins (Rac1, Nox2, p67(phox), SOD1), while
      also retaining specificity for ligand-activated receptor effectors. Our studies
      suggest that TNF-alpha and IL-1 beta signaling pathways both can use Nox2 to
      facilitate redox activation of their respective receptors at the endosomal level
      by promoting the redox-dependent recruitment of TRAFs. These studies help to
      explain how cellular compartmentalization of redox signals can be used to direct
      receptor activation from the plasma membrane.

PMID- 19113819
TI  - Viscoelastic behavior of polyacrylonitrile/dimethyl sulfoxide concentrated
      solution during thermal-induced gelation.
AB  - Thermal-induced gelation of polyacrylonitrile (PAN)/dimethyl sulfoxide (DMSO)
      concentrated solution has been rheologically investigated in relation to
      temperature and aging. Phase behavior of PAN/DMSO solution was studied through
      examining the intrinsic viscosities [eta]. The gelation temperature T(g), gel
      time t(g), and the critical values of relaxation exponent n were obtained by
      measuring the viscoelastic functions (G', G'', tan delta, and eta*) based on the
      Winter and Chambon theory. The solution with higher PAN concentration was found
      to be more sensitive to the temperature, which makes it gel at a higher
      temperature. The n value, however, changes little with varied concentration. The
      gel strength S was found to depend on the concentration of the solution. Gelation
      of the 23 wt % PAN/DMSO solution occurs after being aged at 25 degrees C for a
      period of time, i.e., gel time t(g). The critical n value (S value) at t(g) was
      larger (smaller) than that at T(g) in the cooling process, attributed to the
      different critical feature of the PAN gels formed in different conditions. The
      power law relations eta(0) proportional, variant epsilon(-gamma) and G(e)
      proportional, variant epsilon(z) were found to be valid for PAN/DMSO solution
      before and beyond the gel time t(g), respectively.

PMID- 19113820
TI  - Probing persistent intramolecular C-H...X (X = O, S, Br, Cl, and F) bonding in
      solution using benzyl Meldrum's acid derivatives.
AB  - Persistent intramolecular interactions between acidic C-H hydrogens and a variety
      of acceptors (X) (X = O, S, Br, Cl, and F) in solution were probed by (1)H NMR
      experiments, using 5-benzyl Meldrum's acid derivatives. To bring about formation
      of intramolecular C-H...X bonding, ortho-substituted benzyl Meldrum's acids were
      designed, for which hydrogen bonding occurred through a six-membered ring.
      Introduction of substituents on the aromatic moiety and in the tether allowed
      variation of electronic and steric factors. The superior acidity of Meldrum's
      acids impacted the ability of the C-H hydrogen to engage in nonclassical C-H...X
      bonds and drove the conformational properties of benzyl Meldrum's acid, in
      combination with steric factors, namely A(1,3)-allylic strain. Further
      understanding of intramolecular C-H...X bonds was gained by characterization of
      benzyl Meldrum's acids in the solid state, by X-ray analysis, and by the
      conformation correlated to the observations made in solution.

PMID- 19113821
TI  - Sestrin 2 is not a reductase for cysteine sulfinic acid of peroxiredoxins.
AB  - The active-site cysteine of 2-Cys peroxiredoxins (Prxs), a subgroup of the Prx
      family, is reversibly hyperoxidized to cysteine sulfinic acid during catalysis
      with concomitant loss of peroxidase activity. The reduction of sulfinic 2-Cys Prx
      enzymes, the first known biologic of such a reaction, has been reported to be
      catalyzed by either sulfiredoxin (Srx) or sestrin (Sesn) 2. The 13-kDa Srx and 60
      kDa Sesn 2 show no sequence similarity, however. Whereas the reductase function
      of Srx has been confirmed by several studies, such is not the case for Sesn 2. We
      have now shown that (a) recombinant Sesn 2 did not catalyze the reduction of
      sulfinic Prx I in vitro, whereas Srx did; (b) overexpression of Sesn 2 in HeLa or
      A549 cells did not affect the reduction of 2-Cys Prxs, whereas overexpression of
      Srx markedly increased the reduction rate; and (c) the rate of sulfinic 2-Cys Prx
      reduction in embryonic fibroblasts derived from Sesn 2-knockout mice did not
      differ from that in those derived from wild-type mice. These results suggest
      that, unlike Srx, Sesn 2 is not a sulfinic Prx reductase.

PMID- 19113822
TI  - Room temperature instability of E'gamma centers induced by gamma irradiation in
      amorphous SiO2.
AB  - We study by optical absorption measurements the stability of E'(gamma) centers
      induced in amorphous silica at room temperature by gamma irradiation up to 79
      kGy. A significant portion of the defects spontaneously decay after the end of
      irradiation, thus allowing the partial recovery of the transparency loss
      initially induced by irradiation. The decay kinetics observed after gamma
      irradiation with a 0.6 kGy dose closely resembles that measured after exposure to
      2000 pulses of pulsed ultraviolet (4.7 eV) laser light of 40 mJ/cm(2) energy
      density per pulse. In this regime, annealing is ascribed to the reaction of the
      induced E'(gamma) centers with diffusing H(2) of radiolytic origin. At higher
      gamma doses, the decay kinetics becomes unexpectedly slower notwithstanding the
      progressive growth of the concentration of induced defects. In particular, the
      annealing kinetics of E'(gamma) centers after 79 kGy irradiation is inconsistent
      with the reaction parameters between the defect and H(2). To explain this result,
      on the basis of the quantitative analysis of the kinetics, we propose water
      related species to be responsible for the slow room temperature annealing of
      E'(gamma) after irradiation with such a dose. This model is qualitatively
      supported by results obtained by IR absorption measurements, which show an
      increase of the absorption in the spectral region of Si-OH groups.

PMID- 19113824
TI  - Molecular dynamics simulations on binding models of Dervan-type polyamide +
      Cu(II) nuclease ligands to DNA.
AB  - Molecular dynamics simulations for the ligand [Cu(BPA)](2+) (BPA = bis(2
      pyridylmethyl)amine) nuclease bound to either the single-chain polyamide,
      ImPyImImPybetaDp, or the antiparallel double-polyamide, (ImImImbetaDp)(2), and
      associated with DNA were performed to predict the improvement of selective DNA
      cleavage ability of copper-based chemical nucleases. The results from the
      simulations indicate that either polyamide-bound [Cu(BPA)](2+) + OOH(-) (which is
      a necessary substrate in the redox mechanism of DNA cleavage) can locate in the
      minor groove of DNA in the parallel orientation similar to the X-ray structure.
      As a consequence of the polyamide + [Cu(BPA)](2+) + OOH(-) ligand binding to DNA,
      the active end oxygen atom of the OOH(-) substrate is held in close proximity to
      the known target C1'H or C4'H protons of the DNA. Upon examinations of six
      different ligands binding to DNA, the binding interaction of the entire ligand
      with DNA for each polyamide increases with the presence of [Cu(BPA)](2+) + OOH(-)
      ligand. The N-H groups of the linking regions from polyamide play an important
      role for the interaction by functioning as H-bond donors to N or O atoms of the
      nucleobase located on the floor of the minor groove of DNA. The investigation
      provides the feasible protocol to improve the selective DNA cleavage activity of
      chemical nucleases assisted by DNA recognition agents.

PMID- 19113823
TI  - Vesicle formation and endocytosis: function, machinery, mechanisms, and modeling.
AB  - Vesicle formation provides a means of cellular entry for extracellular substances
      and for recycling of membrane constituents. Mechanisms governing the two primary
      endocytic pathways (i.e., caveolae- and clathrin-mediated endocytosis, as well as
      newly emerging vesicular pathways) have become the focus of intense investigation
      to improve our understanding of nutrient, hormone, and drug delivery, as well as
      opportunistic invasion of pathogens. In this review of endocytosis, we broadly
      discuss the structural and signaling proteins that compose the molecular
      machinery governing endocytic vesicle formation (budding, invagination, and
      fission from the membrane), with some regard for the specificity observed in
      certain cell types and species. Important biochemical functions of endocytosis
      and diseases caused by their disruption also are discussed, along with the
      structures of key components of endocytic pathways and their known mechanistic
      contributions. The mechanisms by which principal components of the endocytic
      machinery are recruited to the plasma membrane, where they interact to induce
      vesicle formation, are discussed, together with computational approaches used to
      simulate simplified versions of endocytosis with the hope of clarifying aspects
      of vesicle formation that may be difficult to determine experimentally. Finally,
      we pose several unanswered questions intended to stimulate further research
      interest in the cell biology and modeling of endocytosis.

PMID- 19113826
TI  - Rigid duplex alpha-cyclodextrin reversibly connected with disulfide bonds.
      Synthesis and inclusion complexes.
AB  - The rigid duplex cyclodextrin 6 composed of two alpha-cyclodextrin macrocycles
      connected with two disulfide bonds in "transannular" (C6(I), C6(IV)) positions
      was prepared from partially debenzylated alpha-cyclodextrin 1 in four steps in
      73% overall yield. In the last key step involving oxidative coupling of the thiol
      5, predominance of the target duplex 6 can be attained under conditions of
      thermodynamic control. The structure of duplex cyclodextrin was established by MS
      as well as 2-D NMR methods and confirmed by a single-crystal X-ray analysis. The
      ability of the duplex cyclodextrin 6 to bind alpha,omega-alkanediols (C9-C14) and
      1-alkanols (C9 and C10) was studied by isothermal titration calorimetry in
      aqueous solutions. The stability constants of the complexes gradually increase
      with the alkyl chain length and reach an unprecedently high value of K = 8.6 x
      10(9) M(-1) for 1,14-tetradecanediol. It was found that the doubly bridged dimer
      6 exhibits higher binding affinity toward the series of alpha,omega-alkanediols
      than the singly bridged analogue 10 by about 2 orders of magnitude in K (M(-1))
      or 3.1-3.3 kcal/mol in deltaG(o), the enhancement being due to enthalpic factors.
      Theoretical calculations using DFT-D methods suggest that the enthalpic
      contribution stems from dispersion interactions.

PMID- 19113827
TI  - Water-assisted atom transfer radical polymerization of N-isopropylacrylamide:
      nature of solvent and temperature.
AB  - We demonstrate here via the atom transfer radical polymerization (ATRP) of N
      isopropylacrylamide (NIPAM) at low temperature that the negative function of
      water in aqueous ATRP is significantly suppressed. By the addition of a small
      amount of water in a water-miscible organic solvent and maintaining low
      polymerization temperature, the ATRP of NIPAM is relatively fast and well
      controlled. We observed that the rate of the polymerization in pure organic
      solvent at a monomer concentration of 20 wt % is slow, and relatively low
      conversions were obtained. The low conversion of PNIPAM in pure alcoholic media
      (such as methanol, ethanol, and n-propanol) is attributed to the poor solubility
      of the resulting low molecular weight polymer in such solvents. The consequence
      is that the PNIPAM chains are aggregated, resulting in the inaccessibility of the
      embedded halide atom of the polymer chain ends by the copper catalyst. As
      expected, the ATRP of NIPAM in pure water was found to be fast and uncontrolled.
      These results have therefore prompted us to study the ATRP of NIPAM in aqueous
      organic mixtures. Room temperature polymerization of NIPAM in mixed aqueous
      organic solvent mixtures (organic:water = 4:1 or 3:1) revealed to be fast and
      uncontrolled. However, when the NIPAM polymerization was conducted at low
      temperature (0 degrees C) in such solvent systems, the polymerization turned out
      to be well-controlled as the molar masses progress linearly with conversion, and
      pseudo-first-order kinetic plots were obtained. Furthermore, monomodal GPC traces
      and narrow molecular weight distributions were obtained in all aqueous-organic
      solvent systems. Chain extension for aqueous ATRP of NIPAM revealed to proceed
      well at low temperature as compared to room temperature. Furthermore, we observe
      that the rates of the polymerization of NIPAM in different aqueous-organic
      mixtures follow the trend of polarity in the case of the polar aprotic solvents.
      However, in the case of polar protic solvent (such as methanol, ethanol, 1
      propanol, and 2-propanol), the rate of the polymerization was found to increase
      with increasing solubility of the PNIPAM from methanol to 2-propanol.

PMID- 19113829
TI  - Thermodynamics and folding pathways of trpzip2: an accelerated molecular dynamics
      simulation study.
AB  - In this paper, we apply an enhanced sampling method introduced earlier to study
      the folding mechanism of a beta-hairpin, trpzip2, using an all-atom potential for
      the protein and an implicit model for the solvent. The enhanced sampling method
      allows us to obtain multiple protein folding and unfolding trajectories in
      relatively short simulations. The sufficient sampling of folding and unfolding
      events of trpzip2 makes possible a more detailed investigation of its folding
      landscape and thermodynamics, leading to the identification of folding pathways.
      The analysis of the thermodynamics involved in the folding of trpzip2 showed that
      this polypeptide folds by two stages: a downhill hydrophobic collapse followed by
      formation of native hydrogen bonds. During the hydrogen bond formation, a
      transition state can be identified with only one native hydrogen bond being
      formed, which is more consistent with a 'zip-out' mechanism. To address the
      dynamics in a more reliable way, explicit solvent was used for the estimation of
      the diffusion constant, which was used in the Kramer's theory, together with the
      free energy profile calculated using the enhanced sampling and the implicit
      solvent, to calculate the folding rate. The calculated folding time agrees well
      with the experimental value of 2.5 micros.

PMID- 19113831
TI  - Development of a nanoLC LTQ orbitrap mass spectrometric method for profiling
      glycans derived from plasma from healthy, benign tumor control, and epithelial
      ovarian cancer patients.
AB  - We report the development of split-less nano-flow liquid chromatography mass
      spectrometric analysis of glycans chemically cleaved from glycoproteins in
      plasma. Porous graphitized carbon operating under reverse-phase conditions and an
      amide-based stationary phase operating under hydrophilic interaction conditions
      are quantitatively compared for glycan separation. Both stationary phases
      demonstrated similar column efficiencies and excellent retention time
      reproducibility without an internal standard to correct for retention time shift.
      The 95% confidence intervals of the mean retention times were +/-4 s across 5
      days of analysis for both stationary phases; however, the amide stationary phase
      was observed to be more robust. The high mass measurement accuracy of less than 2
      ppm and fragmentation spectra provided highly confident identifications along
      with structural information. In addition, data are compared among samples derived
      from 10 healthy controls, 10 controls with a differential diagnosis of benign
      gynecologic tumors, and 10 diseased epithelial ovarian cancer patients (EOC). Two
      fucosylated glycans were found to be up-regulated in healthy controls and
      provided an accurate diagnostic value with an area under the receiver operator
      characteristic curve of 0.87. However, these same glycans provided a
      significantly less diagnostic value when used to differentiate EOC from benign
      tumor control samples with an area under the curve of 0.73.

PMID- 19113832
TI  - Fluorescent avidin-bound silver particle: a strategy for single target molecule
      detection on a cell membrane.
AB  - Cy5-avidin conjugate-bound silver nanoparticles were prepared as a fluorescence
      molecular reagent for the cell imaging. Compared with the metal-free avidin
      conjugate, the avidin-metal complex was observed to display a stronger emission
      intensity, shorter lifetime, and better photostability. The avidin-metal
      complexes were conjugated with the biotin-sites on the surfaces of PM1 cell
      lines, and the cell images were recorded using scanning confocal microscopy. It
      was noticed that the avidin-metal complexes bound on the cell surfaces could be
      identified as the isolated emission spots distinct from the cellular
      autofluorescence. The emission intensity over the cell image was increased with
      an increase of the number of avidin-metal complexes on the cell surface but the
      lifetime was decreased. A quantitative regression curve was achieved between the
      amount of avidin-metal complex on the cell surface and the emission intensity or
      lifetime over the entire cell image. On the basis of this curve, we expect to
      develop an approach that can be used to quantify the amount of target molecules
      on the cell surfaces using the cell intensity and lifetime images at the single
      cell level.

PMID- 19113833
TI  - Label-free assay for thermodynamic analysis of protein-ligand interactions: a
      multivariate strategy for allosteric ligand screening.
AB  - The binding of allosteric ligands to protein can induce changes to the
      holoprotein conformation, stability, and activity that have an impact on
      unfolding dynamics. Herein we report a label-free strategy for determining the
      dissociation constant of protein-ligand interactions over a wide dynamic range
      (>10(4), Kd from nano- to millimolar) using capillary electrophoresis that
      overcomes the constraints of an ideal two-state protein unfolding model.
      Multivariate analysis of thermodynamic parameters associated with holoprotein
      unfolding and ligand binding is demonstrated for the classification of cyclic
      nucleotide analogues that function as allosteric modulators of regulatory
      proteins, such as the exchange protein directly activated by cAMP (EPAC).

PMID- 19113834
TI  - Protein nuclear magnetic resonance under physiological conditions.
AB  - Almost everything we know about protein biophysics comes from studies on purified
      proteins in dilute solution. Most proteins, however, operate inside cells where
      the concentration of macromolecules can be >300 mg/mL. Although reductionism
      based approaches have served protein science well for more than a century,
      biochemists now have the tools to study proteins under these more physiologically
      relevant conditions. We review a part of this burgeoning postreductionist
      landscape by focusing on high-resolution protein nuclear magnetic resonance (NMR)
      spectroscopy, the only method that provides atomic-level information over an
      entire protein under the crowded conditions found in cells.

PMID- 19113836
TI  - Bivalent ligands with long nanometer-scale flexible linkers.
AB  - High-affinity ligands recognizing biomolecules with high specificity are crucial
      for drug discovery and biomolecule detection. We describe here a simple approach
      to preparing aptamer-based ligands with enhanced binding affinity. In this
      approach, two aptamer ligands with suboptimal binding properties are covalently
      linked with a long flexible linker to create a bivalent ligand with significantly
      improved binding affinity. We first used a simple oligonucleotide-based model,
      which mimicked the interaction between bivalent ligands and their target
      molecules, to investigate the principles governing the affinity enhancement.
      These experiments showed that as long as the individual ligands had at least
      submicromolar binding affinities, they could be linked with a nanometer-scale
      flexible linker to produce bivalent ligands with improved binding affinity and
      specificity. Furthermore, comparison of the experimental data with the bivalent
      ligand properties predicted by a wormlike chain model showed that this model
      provided a good approximation of the binding properties of nanometer-scale
      flexible bivalent ligands. To verify the practicality of bivalent ligands with
      nanometer-scale flexible linkers, we constructed aptamer-based bivalent ligands
      for human alpha-thrombin. In agreement with the predictions derived from the
      model system, the binding affinities and the anticlotting activities of thrombin
      bivalent ligands were significantly improved compared to those of the individual
      ligands.

PMID- 19113835
TI  - Exploring the molecular design of protein interaction sites with molecular
      dynamics simulations and free energy calculations.
AB  - The significant work that has been invested toward understanding protein-protein
      interaction has not translated into significant advances in structure-based
      predictions. In particular redesigning protein surfaces to bind to unrelated
      receptors remains a challenge, partly due to receptor flexibility, which is often
      neglected in these efforts. In this work, we computationally graft the binding
      epitope of various small proteins obtained from the RCSB database to bind to
      barnase, lysozyme, and trypsin using a previously derived and validated
      algorithm. In an effort to probe the protein complexes in a realistic
      environment, all native and designer complexes were subjected to a total of
      nearly 400 ns of explicit-solvent molecular dynamics (MD) simulation. The MD data
      led to an unexpected observation: some of the designer complexes were highly
      unstable and decomposed during the trajectories. In contrast, the native and a
      number of designer complexes remained consistently stable. The unstable
      conformers provided us with a unique opportunity to define the structural and
      energetic factors that lead to unproductive protein-protein complexes. To that
      end we used free energy calculations following the MM-PBSA approach to determine
      the role of nonpolar effects, electrostatics and entropy in binding. Remarkably,
      we found that a majority of unstable complexes exhibited more favorable
      electrostatics than native or stable designer complexes, suggesting that
      favorable electrostatic interactions are not prerequisite for complex formation
      between proteins. However, nonpolar effects remained consistently more favorable
      in native and stable designer complexes reinforcing the importance of hydrophobic
      effects in protein-protein binding. While entropy systematically opposed binding
      in all cases, there was no observed trend in the entropy difference between
      native and designer complexes. A series of alanine scanning mutations of hot-spot
      residues at the interface of native and designer complexes showed less than
      optimal contacts of hot-spot residues with their surroundings in the unstable
      conformers, resulting in more favorable entropy for these complexes. Finally,
      disorder predictions revealed that secondary structures at the interface of
      unstable complexes exhibited greater disorder than the stable complexes.

PMID- 19113837
TI  - (-)-Epigallocatechin-3-gallate is a novel Hsp90 inhibitor.
AB  - (-)-Epigallocatechin-3-gallate (EGCG), a major component of green tea, protects
      against certain types of cancers, although the mechanism has not yet been
      determined. It was previously demonstrated that EGCG blocks aryl hydrocarbon
      receptor (AhR)-mediated transcription induced by the potent carcinogen 2,3,7,8
      tetrachlorodibenzo-p-dioxin (TCDD). Unlike other AhR antagonists that directly
      bind to the AhR, EGCG inhibits AhR-mediated transcription by binding to hsp90. We
      hypothesize that EGCG exerts anti-AhR and anticancer effects by acting as an
      hsp90 inhibitor. Using proteolytic footprinting, immunoprecipitation, and an ATP
      agarose pull-down assay, EGCG was found to directly modulate the conformation of
      hsp90 and bind at or near to a C-terminal ATP binding site. Hsp90 chaperone
      function, as assessed by its ability to mediate refolding of denatured
      luciferase, was inhibited by EGCG treatment. Hsp90 dimerization, which occurs at
      the C-terminal end, was also inhibited by EGCG treatment. Coimmunoprecipitation
      studies showed that EGCG stabilizes an AhR complex that includes hsp90 and XAP2
      (hepatitis B virus X-associated protein 2), and decreases the association of aryl
      hydrocarbon nuclear translocator (Arnt) with ligand-activated AhR. Thus, EGCG,
      through its ability to bind to hsp90, blocks AhR response element (AhRE)
      recognition. These studies indicate a novel mechanism whereby EGCG inhibits
      ligand-induced AhRE binding and AhR-mediated transcriptional activity. In EGCG
      treated human ovarian carcinoma SKOV3 cells, decreased levels of several cancer
      related hsp90 client proteins, such as ErbB2, Raf-1 and phospho-AKT, were
      observed. EGCG also modified the association of hsp90 with several cochaperones.
      Overall, these data indicate that EGCG is a novel hsp90 inhibitor. Further
      studies are needed to determine if this has a role in the antitumor actions of
      EGCG.

PMID- 19113838
TI  - Intrinsically unstructured phosphoprotein TSP9 regulates light harvesting in
      Arabidopsis thaliana.
AB  - Thylakoid-soluble phosphoprotein of 9 kDa, TSP9, is an intrinsically unstructured
      plant-specific protein [Song, J., et al. (2006) Biochemistry 45, 15633-15643]
      with unknown function but established associations with light-harvesting proteins
      and peripheries of both photosystems [Hansson, M., et al. (2007) J. Biol. Chem.
      282, 16214-16222]. To investigate the function of this protein, we used a
      combination of reverse genetics and biochemical and fluorescence measurement
      methods in Arabidopsis thaliana. Differential gene expression analysis of plants
      with a T-DNA insertion in the TSP9 gene using an array of 24000 Arabidopsis genes
      revealed disappearance of high light-dependent induction of a specific set of
      mostly signaling and unknown proteins. TSP9-deficient plants had reduced levels
      of in vivo phosphorylation of light-harvesting complex II polypeptides.
      Recombinant TSP9 was phosphorylated in light by thylakoid membranes isolated from
      the wild-type and mutant plants lacking STN8 protein kinase but not by the
      thylakoids deficient in STN7 kinase, essential for photosynthetic state
      transitions. TSP9-lacking mutant and RNAi plants with downregulation of TSP9
      showed reduced ability to perform state transitions. The nonphotochemical
      quenching of chlorophyll fluorescence at high light intensities was also less
      efficient in the mutant compared to wild-type plants. Blue native electrophoresis
      of thylakoid membrane protein complexes revealed that TSP9 deficiency increased
      relative stability of photosystem II dimers and supercomplexes. It is concluded
      that TSP9 regulates plant light harvesting acting as a membrane-binding protein
      facilitating dissociation of light-harvesting proteins from photosystem II.

PMID- 19113839
TI  - Reaction of AdoMet with ThiC generates a backbone free radical.
AB  - ThiC is an [4Fe-4S] cluster protein that catalyzes the formation of 4-amino-5
      hydroxymethyl-2-methylpyrimidine. EPR spectroscopic studies demonstrate that,
      upon interaction with AdoMet, active ThiC from Salmonella enterica generates a
      persistent free radical on the alpha-carbon of an amino acid residue. The EPR
      properties of the radical are consistent with any residue other than a Gly or
      Ala. Exposure to oxygen was accompanied by a fission of the radical-carrying
      polypeptide chain between the Gly436 and His437 residues in ThiC. Regardless of
      whether the backbone radical is part of the catalytic machinery, its presence
      provides evidence that ThiC employs free radical chemistry as expected for
      radical SAM enzymes.

PMID- 19113843
TI  - Switchable electrode controlled by enzyme logic network system: approaching
      physiologically regulated bioelectronics.
AB  - The logic network composed of three enzymes (alcohol dehydrogenase, glucose
      dehydrogenase, and glucose oxidase) operating in concert as four concatenated
      logic gates (AND/OR), was designed to process four different chemical input
      signals (NADH, acetaldehyde, glucose, and oxygen). The cascade of biochemical
      reactions culminated in pH changes controlled by the pattern of the applied
      biochemical input signals. The "successful" set of inputs produced gluconic acid
      as the final product and yielded an acidic medium, lowering the pH of a solution
      from its initial value of pH 6-7 to the final value of ca. 4. The whole set of
      the input signal combinations included 16 variants resulting in different output
      signals. Those that corresponded to the logic output 1, according to the Boolean
      logic encoded in the logic circuitry, resulted in the acidic medium. The pH
      changes produced in situ were coupled with a pH-sensitive polymer-brush
      functionalized electrode, resulting in the interface switching from the OFF
      state, when the electrochemical reactions are inhibited, to the ON state, when
      the interface is electrochemically active. Soluble [Fe(CN)(6)](3-/4-) was used as
      an external redox probe to analyze the state of the interface and to follow the
      changes produced in situ by the enzyme logic network, depending on the pattern of
      the applied biochemical signals. The chemical signals processed by the enzyme
      logic system and transduced by the sensing interface were read out by
      electrochemical means (cyclic voltammetry and Faradaic impedance spectroscopy).
      This readout step features a "sigmoid" processing of the signals that provides
      "filtering" and significantly suppresses errors. Coupling between signal
      processing enzyme logic networks and electronic transducers will allow future
      "smart" bioelectronic devices to respond to immediate physiological changes and
      provide autonomous signaling/actuation depending on the concentration patterns of
      the physiological markers.

PMID- 19113841
TI  - Effects of binding factors on structural elements in F-actin.
AB  - Understanding the dynamics of the actin filament is essential to a detailed
      description of their interactions and role in the cell. Previous studies have
      linked the dynamic properties of actin filaments (F-actin) to three structural
      elements contributing to a hydrophobic pocket, namely, the hydrophobic loop, the
      DNase I binding loop, and the C-terminus. Here, we examine how these structural
      elements are influenced by factors that stabilize or destabilize F-actin, using
      site-directed spin-labeled (SDSL) electron paramagnetic resonance (EPR),
      fluorescence, and cross-linking techniques. Specifically, we employ cofilin, an
      actin destabilizing protein that binds and severs filaments, and phalloidin, a
      fungal toxin that binds and stabilizes F-actin. We find that cofilin shifts both
      the DNase I binding loop and the hydrophobic loop away from the C-terminus in F
      actin, as demonstrated by weakened spin-spin interactions, and alters the
      environment of spin probes on residues of these two loops. In contrast, although
      phalloidin strongly stabilizes F-actin, it causes little or no local change in
      the environment of the loop residues. This indicates that the stabilizing effect
      of phalloidin is achieved mainly through constraining structural fluctuations in
      F-actin and suggests that factors and interactions that control these
      fluctuations have an important role in the cytoskeleton dynamics.

PMID- 19113844
TI  - Mechanism of antibacterial action of dermaseptin B2: interplay between helix
      hinge-helix structure and membrane curvature strain.
AB  - Dermaseptin B2 (Drs B2) is a 33-residue-long cationic, alpha-helical
      antimicrobial peptide endowed with membrane-damaging activity against a broad
      spectrum of microorganisms, including bacteria, yeasts, fungi, and protozoa, but
      its precise mechanism of action remained ill-defined. A detailed characterization
      of peptide-membrane interactions of Drs B2 was undertaken in comparison with a C
      terminal truncated analogue, [1-23]-Drs B2, that was virtually inactive on
      bacteria despite retaining the cationic charge of the full-length peptide. Both
      peptides were tested on living cells using membrane permeabilization assays and
      on large unilamellar and multilamellar phospholipid vesicles composed of binary
      lipid mixtures by dye leakage assay, fluorescence spectroscopy, circular
      dichroism, and differential scanning calorimetry and also on SDS micelles using
      NMR spectroscopy. The results indicate that Drs B2 induces a strong perturbation
      of anionic lipid bilayers, resides at the hydrocarbon core-water interface,
      parallel to the plane of the membrane, and interacts preferentially with the
      polar head groups and glycerol backbone region of the anionic phospholipids, as
      well as the region of the lipid acyl chain near the bilayer surface. The
      interfacial location of Drs B2 induces a positive curvature of the bilayer and
      clustering of anionic lipids, consistent with a carpet mechanism, that may lead
      to the formation of mixed peptide-phospholipid toroidal, transient pores and
      membrane permeation/disruption once a threshold peptide accumulation is reached.
      In constrast, the truncated [1-23]-Drs B2 analogue interacts at the head group
      level without penetrating and perturbing the hydrophobic core of the bilayer. NMR
      study in SDS micelles showed that [1-23]-Drs B2 adopts a well-defined helix
      encompassing residues 2-20, whereas Drs B2 was previously found to adopt helical
      structures interrupted around the Val(9)-Gly(10) segment. Thus the antibacterial
      activity of Drs B2 depends markedly on a threshold number of hydrophobic residues
      to be present on both extremities of the helix. In a membrane environment with a
      strong positive curvature strain, Drs B2 can adopt a flexible helix-hinge-helix
      structure that facilitates the concomitant insertion of the strongly hydrophobic
      N- and C-termini of the peptide into the acyl core of the membrane.

PMID- 19113845
TI  - Anion-controlled pore size of titanium silicate molecular sieves.
AB  - Titanium silicate molecular sieves contain structural units that are
      fundamentally different from classical aluminosilicates. In addition to ordered
      octahedral titanium chains, members of the zorite family contain pentagonal
      titanium units which project into the main adsorption channels of the framework.
      We report that the effective pore size of these materials can be controlled by
      substituting halogens at the O7 sites that cap the pentagonal pyramids projecting
      into the channel. The quantity and type of halogen used determines the adsorptive
      properties of the molecular sieve. Barium exchange stabilizes these materials
      over a wide temperature range (nominally 200-400 degrees C). The barium-exchanged
      materials do not contract appreciably with calcination, as is observed in related
      Molecular Gate materials, and thus halogen content can control the pore size of
      the materials. This new approach to pore size control may have important
      implications for the purification of multiple classes of compounds, including
      light hydrocarbons and permanent gases.

PMID- 19113846
TI  - Transition states and nonlinear excitations in chloroform observed with a sub-5
      fs pulse laser.
AB  - Sub-5 fs pulse dynamics observed in neat chloroform (CHCl(3)) and the
      CHCl(3)...O(2) charge-transfer complex in oxygen-saturated chloroform (O(2)
      CHCl(3)) were found to be dominated by wave packet motions in the excited state
      and the ground state, respectively. The time-resolved signal of CHCl(3) exhibits
      dynamics in the electronic excited state generated by a three-photon absorption
      process, and that of O(2)-CHCl(3) is explained in terms of the dynamics of the
      electronic ground state excited by the stimulated Raman process. In addition, we
      found that the oxidation reaction of chloroform in the charge-transfer complex of
      chloroform and oxygen easily proceeds via a C-H insertion process triggered by
      the stimulated Raman process under the irradiation of a visible laser pulse. The
      spectrogram analysis enabled direct observation of the real-time dynamics of the
      Raman-triggered oxidation process. These results demonstrate that observation of
      transition states by sub-5 fs time-resolved spectroscopy is applicable to "ground
      state reactions" as well as "excited-state reactions" via stimulated Raman
      excitation in a wide variety of chemical reactions.

PMID- 19113847
TI  - Mounting freestanding molecular functions onto surfaces: the platform approach.
AB  - A modular system has been developed to mount molecules upright onto metal
      surfaces in a well controlled geometry. The approach is based on a reactive
      platform (triazatriangulenium salt) with an electrophilic center. Functional
      molecules are attached via C-C bond formation. The distance from the surface can
      be varied by a spacer, and the distance of the functional units from each other
      by the size of the platform. Self-assembly of the parent triazaangulenium salt as
      well as the functionalized platforms on Au(111) surfaces results in stable,
      hexagonally ordered adlayers.

PMID- 19113848
TI  - Synthesis, photophysical behavior, and electronic structure of push-pull purines.
AB  - "Push-pull" purines have been synthesized by the introduction of electron
      accepting functional groups (A = CN, CO(2)Me, and CONHR) to the heterocyclic C(8)
      position to complement typical electron-donating substituents at C(2) (D(1)) and
      C(6) (D(2)). The donor-acceptor purines show significantly altered, and overall
      improved photophysical properties relative to their acceptor-free precursors (A =
      H); these include red-shifted (20-50 nm) absorption maxima, highly solvatochromic
      emission profiles (em lambda(max) from 355-466 nm depending on substitution
      pattern and solvent) with excellent linear correlations between emission energy
      and solvent polarity (E(T)(N)), improved photochemical stability upon continuous
      irradiation, and enhanced (up to 2500%) fluorescence quantum yields.
      Comprehensive structure-property studies show how the absorption/emission maxima
      and quantum yields depend on donor and acceptor structure, relative donor
      position (C(2) or C(6)), and solvent (1,4-dioxane, dichloromethane, acetonitrile,
      methanol, and in some cases water). Further insight regarding electronic
      structure comes from a quantitative treatment of the solvent-dependent emission
      data (that provides Delta mu(ge) values ranging from 1.9 to 3.4 D) and DFT
      (B3LYP/6-311++G**) electronic structure calculations. X-ray crystal structures of
      several derivatives showcase the molecular recognition capabilities of the donor
      acceptor chromophores that overall have photophysical and structural properties
      suitable for applications in biosensing and materials.

PMID- 19113849
TI  - Cucurbit[n]uril-polyoxoanion hybrids.
AB  - The first organic-inorganic hybrid complexes between CB[n] and polyoxometalates
      not only display a surprisingly high structural complementarity, the right
      pairing also allows their chemical and physical properties to be coupled, as
      illustrated by two examples.

PMID- 19113850
TI  - Catalytic asymmetric conjugate addition of simple alkyl thiols to alpha,beta
      unsaturated N-acylated oxazolidin-2-ones with bifunctional catalysts.
AB  - In this communication, we describe an unprecedented highly enantioselective
      catalytic conjugate addition of simple alkyl thiols to alpha,beta-unsaturated N
      acylated oxazolidin-2-ones catalyzed by acid-base bifunctional catalysis. This
      reaction provides a useful catalytic method for the synthesis of optically active
      chiral sulfur compounds that are otherwise difficult to prepare by asymmetric
      catalysis. The successful development of this reaction resulted from a discovery
      that, upon proper modification, a cinchona alkaloid bearing a thiourea
      functionality at 6' position can afford highly efficient catalysis for asymmetric
      conjugate additions.

PMID- 19113851
TI  - Bending a bond within an individual adsorbed molecule.
AB  - Inelastic electron tunneling manipulation of a bond within chloronitrobenzene
      molecules on Cu(111) shows that the energy costs for bond bending within a
      molecule might be partially gained through better adsorption sites of the
      involved atoms. The chlorine either keeps its gas phase angle and is adsorbed
      near an on-top site or gets distorted to be adsorbed near a hollow site. Noise
      analysis reveals that the excitation of several vibrational modes may initiate
      this bond bending.

PMID- 19113852
TI  - Charge recombination in DNA hairpins controlled by counterions.
AB  - The slow charge recombination in DNA hairpins of various lengths is investigated.
      The distance dependence for the charge recombination rate between stilbene donor
      (Sd(+)) and stilbene acceptor (Sa(-)) linkers separated by AT bridges of various
      lengths has the double exponential form. We suggest that this puzzling dependence
      is associated with two tunneling channels distinguished by the presence or
      absence of a Cl(-) counterion bound to an Sd(+) linker. When Cl(-) is associated
      with Sd(+) the energy of positive charge is lower compared to Sd(+) without a
      counterion. Therefore the potential barrier for charge recombination is higher in
      the presence of Cl(-) bound to Sd(+), and the recombination is characterized by
      the larger tunneling exponent than the tunneling exponent in the absence of
      counterions. Experiment-based estimates of binding parameters agree within
      reasonable expectations. The control experiment replacing the Cl(-) ion with
      other ions is suggested. This replacement enables the control of the charge
      recombination rate modifying it in either direction by orders of magnitude.

PMID- 19113853
TI  - Insights into templated supramolecular polymerization: binding of naphthalene
      derivatives to ssDNA templates of different lengths.
AB  - We report on two diaminotriazine-equipped naphthalene derivatives that bind
      reversibly to a single-stranded DNA template or "tape-measure molecule" via
      hydrogen bonding, yielding monodisperse double-stranded DNA hybrids with one
      strand consisting of a supramolecular naphthalene backbone. These assemblies have
      been investigated extensively, both experimentally and theoretically. The
      structure and the templated self-assembly process of the complex have been
      characterized with UV-vis spectroscopy, circular dichroism spectroscopy,
      molecular dynamics simulations, cryo-transmission electron microscopy, liquid
      atomic force microscopy, electrospray ionization mass spectrometry, light
      scattering, and 1H NMR and infrared spectroscopy. We have found that the DNA
      hybrid complexes have a right-handed helical arrangement stabilized by pi-pi
      interactions and hydrogen bonds. The hydrophilic hydroxyl group at the end of the
      ethylene glycol of the guest molecule suppressed both the nontemplated self
      assembly of the naphthalene guest molecules and the further aggregation of the
      entire DNA hybrid complex. Through the use of a theoretical mass-action model for
      the templated self-assembly, the host-guest and guest-guest interaction energies
      were estimated by fitting to the spectroscopic data. The differently estimated
      values of the interaction energies and thermodynamic parameters vary within
      experimental error, showing the self-consistency of the model. From the obtained
      correlation between the positions of the guest molecules bound on the template,
      we have obtained a qualitative theoretical picture of the way in which the guests
      are physically distributed on the templates. For short templates, the templates
      are filled one-by-one, even at moderate fractions of bound sites. For larger
      templates, the templates first have alternating sequences of filled and empty
      sections, after which, at large fractions of bound sites, virtually all of the
      binding sites for all template lengths are filled.

PMID- 19113854
TI  - ZnO-templated synthesis of wurtzite-type ZnS and ZnSe nanoparticles.
AB  - The controllable synthesis of semiconductor nanocrystals is important for
      exploiting their size-dependent properties in a variety of applications. The
      important wide-bandgap semiconductors ZnS and ZnSe crystallize in both the
      zincblende (ZB) and wurtzite (WZ) structures. While the ZB polymorphs are most
      stable, methods exist for synthesizing the WZ-type nanocrystals. However, because
      of the subtle structural differences between the ZB and WZ structures, subtle
      synthetic differences can favor one polymorph over the other. It is therefore
      challenging to predictably generate the WZ polymorphs and understand the factors
      that play a key role in their formation. Through careful mechanistic studies, we
      show that ZnO nanoparticles, which adopt the WZ structure, form as intermediates
      in typical reactions that generate WZ-ZnS. This implies that ZnO nanoparticles
      can serve as structural templates for the preferential formation of WZ-ZnS
      nanoparticles, and this is confirmed experimentally. Similar chemistry can be
      used to preferentially form WZ-ZnSe and ZB-ZnSe.

PMID- 19113855
TI  - Consequences of a linear two-coordinate geometry for the orbital magnetism and
      Jahn-Teller distortion behavior of the high spin iron(II) complex Fe[N(t-Bu)2]2.
AB  - Mossbauer, EPR, magnetic susceptibility, and DFT studies of the unusual two
      coordinate iron(II) amide Fe[N(t-Bu)(2)](2) show that it retains a linear N-Fe-N
      framework due to the nonbonding delta nature of the (xy, x(2)-y(2)) orbitals. The
      resulting near-degenerate ground state gives rise to a large magnetic moment and
      a remarkably large internal hyperfine field. The results confirm that
      extraordinary orbital magnetic effects can arise in linear transition metal
      complexes in which orbital degeneracies are not broken by Jahn-Teller or Renner
      Teller distortions.

PMID- 19113856
TI  - Giant dendritic molecular electrochrome batteries with ferrocenyl and
      pentamethylferrocenyl termini.
AB  - Giant redox dendrimers were synthesized with ferrocenyl and pentamethylferrocenyl
      termini up to a theoretical number of 3(9) tethers (seventh generation).
      Lengthening of the tethers proved to be a reliable strategy to overcome the bulk
      constraint at the dendrimers periphery. These redox metallodendrimers were
      characterized by (1)H, (13)C, and (29)Si NMR; MALDI-TOF mass spectrometry (for
      the low generations); elemental analysis; UV-vis spectroscopy; dynamic light
      scattering (DLS); atomic force microscopy (AFM); electron-force microscopy (EFM)
      for half- or fully oxidized dendrimers; cyclic voltammetry; and coulometry. UV
      vis spectroscopy, coulometry, and analytical data are consistent with an
      increasing amount of defects as the generation number increases, with this amount
      remaining relatively weak up to G(5). AFM shows that the dendrimers form
      aggregates of discrete size on the mica surface, recalling the agglomeration of
      metal atoms in monodisperse nanoparticles. Cyclic voltammetry reveals full
      chemical and electrochemical reversibility up to G(7), showing that electron
      transfer is fast among the flexible peripheral redox sites. Indeed, the redox
      stability of these new electrochromic dendrimers, i.e., a battery behavior, was
      established by complete chemical oxido-reduction cycles, and the blue 17-electron
      ferrocenium and deep-green mixed-valence Fe(III)/Fe(II) dendritic complexes were
      isolated and characterized. AFM studies also show the reversible dendrimer size
      changes from upon redox switching between Fe(II) and Fe(III), suggesting a
      breathing mechanism controlled by the redox potential. Considerable adsorption of
      high-generation dendrimers on Pt electrodes such as G(7)-Fc allows the easy
      formation of modified electrodes that sense the ATP anion only involving the
      electrostatic factor even in the absence of any other type of interaction with
      the redox tethers.

PMID- 19113857
TI  - Weakly bound molecules in the atmosphere: a case study of HOOO.
AB  - Weakly bound molecules--particularly hydrated complexes of abundant atmospheric
      species--have long been postulated to play an important role in atmospherically
      relevant reactions. For example, such complexes could seed cloud formation and
      alter the global radiation budget. In this Account, we initially describe the
      current data on weakly bound species produced in association reactions of the
      hydroxyl radical (OH) with molecular partners, particularly oxygen (O(2)), nitric
      acid (HONO(2)), and nitrogen dioxide (NO(2)). Researchers have identified weakly
      bound association products of these reactions as the hydrogen trioxy (HOOO)
      radical, the doubly hydrogen-bonded OH-HONO(2) complex, and peroxynitrous acid
      (HOONO), respectively. In each case, previous kinetic studies of the reaction or
      OH vibrational relaxation processes have indicated unusual, non-Arrhenius
      behavior. Under the temperature-pressure conditions of the Earth's lower
      atmosphere, these processes exhibit a negative temperature dependence, indicative
      of an attractive interaction, or a pressure dependence. Researchers have
      subsequently carried out extensive theoretical studies of the properties of these
      weakly bound molecules, but the theoretical studies have lacked experimental
      validation. Next, we describe experimental studies to determine the vibrational
      frequencies and stability of HOOO as a prototypical example of these weakly bound
      molecules. We then use these data to assess its importance in the atmosphere. We
      discuss the efficient production of the HOOO radical from OH and O(2) under
      laboratory conditions and its subsequent detection using infrared action
      spectroscopy, a highly sensitive and selective double resonance technique. Using
      excitation of OH stretch and combination bands comprising OH stretch with lower
      frequency modes, we obtain detailed spectroscopic information on the vibrational
      modes of the two conformers of HOOO. In addition, we infer fundamental
      information about the dissociation dynamics from the OH product state
      distribution, which provides insight into the chemical bonding in HOOO. Perhaps
      most importantly, we utilize a simple conservation of energy relationship based
      on the highest energetically open OH product state to derive a rigorous upper
      limit for the stability of HOOO relative to the OH + O(2) asymptote of 5.3 kcal
      mol(-1). When combined with previous experimental rotational constants that
      reflect the structure of the HOOO radical, our laboratory characterization of its
      stability and vibrational frequencies provides critical information to assess its
      thermochemical properties. Using standard statistical mechanics approaches, we
      can calculate the likely atmospheric abundance of HOOO. We estimate that up to
      25% of the OH radicals in the vicinity of the tropopause may be associated with
      O(2) as a weakly bound molecule.

PMID- 19113858
TI  - Competition between reversible aggregation and loop formation in denatured iso-1
      cytochrome c.
AB  - The competition between intramolecular histidine-heme loop formation and ligand
      mediated oligomer formation in the denatured state is investigated for two yeast
      iso-1-cytochrome c variants, AcH26I52 and AcA25H26I52. Besides the native His 18
      heme ligand, both variants contain a single His at position 26. The AcA25H26I52
      variant has Pro 25 mutated to Ala. The concentration dependence of the apparent
      pK(a) for His 26-heme binding in 3 M guanidine hydrochloride indicates that the
      P25A mutation disfavors oligomerization mediated by intermolecular heme ligation
      by 10-fold. Single- and double-pH-jump stopped-flow experiments with the AcH26I52
      variant show that fast phases for His-heme bond formation and breakage are due to
      intramolecular loop formation and slow phases for His-heme bond formation and
      breakage are due to intermolecular aggregation. The presence of two closely
      spaced slow phases in the kinetics of loop formation for both variants suggests
      that intermolecular His 26-heme ligation results in both dimers and higher-order
      aggregates. The P25A mutation slows formation and speeds breakdown of an initial
      dimer, demonstrating a strong effect of local sequence on aggregation. Analysis
      of the kinetic data yields equilibrium constants for intramolecular loop
      formation and intermolecular dimerization at pH 7.1 and indicates that the rate
      constant for intermolecular aggregation is very fast at this pH (10(7)-10(8) M(
      1) s(-1)). In light of the very fast rates of aggregation in the denatured state,
      comparison of models involving reversible or irreversible oligomerization steps
      suggests that equilibrium control of the partitioning between folding and
      aggregation is advantageous for productive protein folding in vivo.

PMID- 19113859
TI  - A highly selective luminescent sensor for the time-gated detection of potassium.
AB  - A terbium complex with long luminescence lifetime for the selective time-gated
      detection of potassium is presented. The complex demonstrates high sensitivity
      with a 25-fold increase in time-gated luminescence intensity between 0 and 15 mM
      potassium. The high selectivity of the complex for potassium over other
      physiological cations, and especially sodium (93 fold), is likely due to a
      favorable cation-pi interaction between a phenol moiety and the potassium ion.

PMID- 19113861
TI  - Synthesis and biological activity of human neuropeptide S analogues modified in
      position 5: identification of potent and pure neuropeptide S receptor
      antagonists.
AB  - Neuropeptide S (NPS), the endogenous ligand of a previously orphan receptor now
      named NPSR, regulates various biological functions in the brain, including
      arousal, locomotion, anxiety, and food intake. Here we report on a focused
      structure-activity study of Gly5, which has been replaced with L and D amino
      acids. Fifteen NPS related peptides were synthesized and pharmacologically tested
      for intracellular calcium mobilization using HEK293 cells stably expressing the
      mouse NPSR. The results of this study demonstrated that peptide potency is
      inversely related to the side chain size, while peptide efficacy strongly depends
      on the relative L and D configuration, with the L amino acids favoring agonist
      while D amino acids display antagonist pharmacological activity. [D-Val5]NPS
      behaved as NPSR pure antagonist in HEK293(mNPSR) cells showing the highest
      potency (pK(B) 7.56) among this series of peptides. The antagonist action of [D
      Val5]NPS was confirmed in vivo in mice, where the peptide at a dose of 10 nmol
      completely blocked the stimulatory effect of 0.1 nmol NPS on locomotor activity.

PMID- 19113860
TI  - Chemical tools for K(+) channel biology.
AB  - K(+) channels are revered for their universal action of suppressing electrical
      activity in nerve and muscle, as well as regulating salt and water transport in
      epithelial tissues involved in metabolism and digestion. These multisubunit
      membrane-embedded proteins carry out their physiological chore, selectively
      allowing the passage of potassium across the membrane, in response to changes in
      membrane voltage and ligand concentration. Elucidating the diverse gating
      properties of K(+) channels is of great biological interest since their molecular
      motions provide insight into how these structurally similar proteins function in
      a wide variety of tissues. Armed with patch clamps, chart recorders, and now high
      resolution structures, electrophysiologists have been dipping into the top tray
      of the chemist's tool box: synthesizing cysteine-modifying agents and organic
      cations and grinding up insects, spiders, and other vermin to isolate natural
      products to poke, probe, and prod K(+) channels. Recently, there has been further
      cross-fertilization between chemists and K(+) channelologists, resulting in
      greater accessibility to more elaborate synthetic methodologies and screening
      approaches. In this review, we catalogue the evolution of chemical tools and
      approaches that have been utilized to elucidate the mechanistic underpinnings of
      K(+) channel biology.

PMID- 19113862
TI  - Dimethylzinc-initiated radical reactions.
AB  - Developments in modern organic synthesis owe much to the field of radical
      chemistry. Mild reaction conditions, high selectivity, good functional group
      tolerance and high product yield are features that have made reactions involving
      radical species indispensable tools for synthetic chemists. In part, the
      discovery of new radical initiators has led to the efficiency that now
      characterizes most radical reactions. This Account describes our investigations
      of radical reactions initiated by dimethylzinc. In 2001, we unexpectedly observed
      this reaction while investigating the amidophosphane-copper-catalyzed asymmetric
      addition of dimethylzinc to N-sulfonyl imines with tetrahydrofuran (THF) as
      reaction solvent. However, instead of adding the desired methyl group to the N
      sulfonyl imine, we produced the THF adduct in excellent yield. This result laid
      the foundation for our discovery of novel modes of reactivity. Further
      investigations of the unexpected addition reaction revealed that a trace amount
      of air was needed for reaction progress, indicating that radical intermediates
      were involved. Indeed, controlled injection of air into the reaction flask by a
      syringe pump through a sodium hydroxide tube afforded the products in good to
      excellent yield. In addition, the reaction proved to be chemoselective for a C=N
      bond over a C=O bond, as well as for 1,4-addition over 1,2-addition. We developed
      asymmetric variants of the radical addition reaction of ethers to imines using
      chiral N-sulfinyl imines to produce the adducts in reasonably high
      stereoselectivity (up to 11:1). A 93:7 diastereomeric ratio of the adduct was
      obtained when bis(8-phenylmenthyl) benzylidenemalonate was used in the radical
      addition of ethers to C=C bonds. Interestingly, in the presence of dimethylzinc
      and air, arylamines, alkoxyamines, and dialkylhydrazines react with THF to give
      amino alcohols, oximes, and hydrazones, respectively, in moderate to high yields.
      We performed a tin-free intermolecular addition of functionalized primary alkyl
      groups, generated from their corresponding iodides, to N-sulfonyl imines using
      dimethylzinc, air, boron trifluoride diethyl etherate, and a catalytic amount of
      copper(II) triflate. Direct C-H bond cleavage from cycloalkanes was also feasible
      in the presence of dimethylzinc, air, and boron trifluoride diethyl etherate to
      give the corresponding cycloalkyl radicals, which were suitable nucleophiles for
      N-sulfonyl imines. In all of the above reactions, dimethylzinc was a superior
      radical initiator than other conventional initiators such as dibenzoyl peroxide,
      diethylzinc, and triethylborane. We hope the coming decades will witness the
      report of other novel radical initiators that would complement the reactivity
      modes of existing ones.

PMID- 19113863
TI  - High-potential C112D/M121X (X = M, E, H, L) Pseudomonas aeruginosa azurins.
AB  - Site-directed mutagenesis of Pseudomonas aeruginosa azurin C112D at the M121
      position has afforded a series of proteins with elevated Cu(II/I) reduction
      potentials relative to the Cu(II) aquo ion. The high potential and low axial
      hyperfine splitting (Cu(II) electron paramagnetic resonance A( parallel)) of the
      C112D/M121L protein are remarkably similar to features normally associated with
      type 1 copper centers.

PMID- 19113864
TI  - Induced association of mu opioid (MOP) and type 2 cholecystokinin (CCK2)
      receptors by novel bivalent ligands.
AB  - Both mu-opioid (MOP) and type 2 cholecystokinin (CCK2) receptors are present in
      areas of the central nervous system that are involved in modulation of pain
      processing. We conducted bioluminescence resonance energy transfer (BRET) studies
      on COS cells coexpressing MOP and CCK2 receptors to determine whether receptor
      heterodimerization is involved in such modulation. These studies revealed the
      absence of constitutive or monovalent ligand-induced heterodimerization.
      Heterodimerization of MOP and CCK2 receptors therefore is unlikely to be
      responsible for the opposing effects between morphine and CCK in the CNS.
      However, association was induced, as indicated by a positive BRET signal, on
      exposure of the cells to bivalent ligands containing mu-opioid agonist and CCK2
      receptor antagonist pharmacophores linked through spacers containing 16-22 atoms
      but not with a shorter (9-atom) spacer. These studies demonstrate for the first
      time that an appropriately designed bivalent ligand is capable of inducing
      association of G-protein-coupled receptors. The finding that opioid tolerance
      studies with these ligands in mice showed no correlation with the BRET data is
      consistent with the absence of association of MOP and CCK2 receptors in vivo.

PMID- 19113865
TI  - Dual integrin and gastrin-releasing peptide receptor targeted tumor imaging using
      18F-labeled PEGylated RGD-bombesin heterodimer 18F-FB-PEG3-Glu-RGD-BBN.
AB  - Radiolabeled RGD and bombesin peptides have been extensively investigated for
      tumor integrin alpha(v)beta(3) and GRPR imaging, respectively. Due to the fact
      that many tumors are both integrin and GRPR positive, we designed and synthesized
      a heterodimeric peptide Glu-RGD-BBN, which is expected to be advantageous over
      the monomeric peptides for dual-receptor targeting. A PEG(3) spacer was attached
      to the glutamate alpha-amino group of Glu-RGD-BBN to enhance the (18)F labeling
      yield and to improve the in vivo kinetics. PEG(3)-Glu-RGD-BBN possesses the
      comparable GRPR and integrin alpha(v)beta(3) receptor-binding affinities as the
      corresponding monomers, respectively. The dual-receptor targeting properties of
      (18)F-FB-PEG(3)-Glu-RGD-BBN were observed in PC-3 tumor model. (18)F-FB-PEG(3)
      Glu-RGD-BBN with high tumor contrast and favorable pharmacokinetics is a
      promising PET tracer for dual integrin and GRPR positive tumor imaging. This
      heterodimer strategy may also be an applicable method to develop other molecules
      with improved in vitro and in vivo characterizations for tumor diagnosis and
      therapy.

PMID- 19113866
TI  - Design, structure-activity relationships and in vivo characterization of 4-amino
      3-benzimidazol-2-ylhydroquinolin-2-ones: a novel class of receptor tyrosine
      kinase inhibitors.
AB  - The inhibition of key receptor tyrosine kinases (RTKs) that are implicated in
      tumor vasculature formation and maintenance, as well as tumor progression and
      metastasis, has been a major focus in oncology research over the last several
      years. Many potent small molecule inhibitors of vascular endothelial growth
      factor receptor (VEGFR) and platelet-derived growth factor receptor (PDGFR)
      kinases have been evaluated. More recently, compounds that act through the
      complex inhibition of multiple kinase targets have been reported and may exhibit
      improved clinical efficacy. We report herein a series of potent, orally
      efficacious 4-amino-3-benzimidazol-2-ylhydroquinolin-2-one analogues as
      inhibitors of VEGF, PDGF, and fibroblast growth factor (FGF) receptor tyrosine
      kinases. Compounds in this class, such as 5 (TKI258), are reversible ATP
      competitive inhibitors of VEGFR-2, FGFR-1, and PDGFRbeta with IC(50) values <0.1
      microM. On the basis of its favorable in vitro and in vivo properties, compound 5
      was selected for clinical evaluation and is currently in phase I clinical trials.

PMID- 19113870
TI  - Application of a hybrid variable selection method for determination of
      carbohydrate content in soy milk powder using visible and near infrared
      spectroscopy.
AB  - Visible and near-infrared (Vis-NIR) spectroscopy was investigated to fast
      determine the carbohydrate content in soy milk powder. A hybrid variable
      selection method was proposed. In this method, a simulate annealing (SA)
      algorithm was first operated to search the optimal band (OB) in the wavelet
      packet transform (WPT) tree. The OB with 47 variables was further selected by SA
      (WTP-OB-SA). Finally, the number of variables was reduced from 47 to 20. The best
      partial least-squares prediction with a high residual predictive deviation (RPD)
      value of 12.2242 was obtained using these 20 variables with the correlation
      coefficient (r) and root-mean-square error of prediction (RMSEP) being 0.9967 and
      0.1669, respectively. The results indicated that Vis-NIR spectroscopy could
      efficiently determine the carbohydrate content in soy milk powder. The WPT-OB-SA
      selection method eliminated redundant variables and improved the prediction
      ability.

PMID- 19113867
TI  - Design and stereoselective preparation of a new class of chiral olefin metathesis
      catalysts and application to enantioselective synthesis of quebrachamine:
      catalyst development inspired by natural product synthesis.
AB  - A total synthesis of the Aspidosperma alkaloid quebrachamine in racemic form is
      first described. A key catalytic ring-closing metathesis of an achiral triene is
      used to establish the all-carbon quaternary stereogenic center and the
      tetracyclic structure of the natural product; the catalytic transformation
      proceeds with reasonable efficiency through the use of existing achiral Ru or Mo
      catalysts. Ru- or Mo-based chiral olefin metathesis catalysts have proven to be
      inefficient and entirely nonselective in cases where the desired product is
      observed. In the present study, the synthesis route thus serves as a platform for
      the discovery of new olefin metathesis catalysts that allow for efficient
      completion of an enantioselective synthesis of quebrachamine. Accordingly, on the
      basis of mechanistic principles, stereogenic-at-Mo complexes bearing only
      monodentate ligands have been designed. The new catalysts provide significantly
      higher levels of activity than observed with the previously reported Ru- or Mo
      based complexes. Enantiomerically enriched chiral alkylidenes are generated
      through diastereoselective reactions involving achiral Mo-based bispyrrolides and
      enantiomerically pure silyl-protected binaphthols. Such chiral catalysts initiate
      the key enantioselective ring-closing metathesis step in the total synthesis of
      quebrachamine efficiently (1 mol % loading, 22 degrees C, 1 h, >98% conversion,
      84% yield) and with high selectivity (98:2 er, 96% ee).

PMID- 19113871
TI  - Bioactivity-guided fractionation and GC/MS fingerprinting of Angelica sinensis
      and Angelica archangelica root components for antifungal and mosquito deterrent
      activity.
AB  - Bioassay-guided fractionation of the chloroform extract from the roots of
      Angelica sinensis led to isolation and characterization of (Z)-ligustilide using
      direct-bioautography with Colletotrichum species. The structure of (Z)
      ligustilide was confirmed by (1)H and (13)C NMR spectroscopy and GC/MS. (Z)
      Ligustilide deterred the biting of two mosquito species more effectively than
      DEET. Three different A. sinensis accessions and one Angelica archangelica root
      oil were evauated by GC and GC/MS, and the dominant component in A. sinensis was
      61-69% (Z)-ligustilide. Two other prominent compounds in A. sinensis oils were
      5.7-9.8% (E)-3-butylidene phthalide and 1.5-2.3% (Z)-3-butylidene phthalide. The
      main constituents that comprised A. archangelica oil were monoterpene
      hydrocarbons such as 24.5% alpha-pinene, 13.8% delta-3-carene, 10.1% beta
      phellandrene, 8.8% p-cymene, 8.4% limonene, and 6.3% sabinene. Phthalides and
      monoterpene hydrocarbons were determined to be good systematic markers or
      chemical fingerprints for A. sinensis and A. archangelica root oils. Chemical
      fingerprinting by GC/MS of A. sinensis also confirmed the misidentification of
      one A. archangelica sample sold in the Chinese market.

PMID- 19113872
TI  - Enzymatic re-esterification of lower glycerides from soybean oil with conjugated
      linoleic acid (CLA).
AB  - New structured lipids essentially free of saturated fatty acids and rich in
      essential fatty acids and CLA were prepared from soybean oil using a selective
      enzymatic procedure of synthesis. Saturated fatty acids originally present in the
      oil were selectively removed in a selective alcoholysis step. Enzymatic re
      esterification with conjugated linoleic acid (CLA) of lower glycerides (di- and
      monoglycerides) obtained from soybean oil was studied using several commercially
      available lipases. Higher maximum reaction conversions were obtained with the
      free acid form of CLA than with the corresponding ethyl ester. Reactions with
      Novozym 435 were fastest, producing 84% diacylglycerols (DAG) in 0.5 h of
      reaction at 60 degrees C. For Lipozyme RM IM the maximum yields of
      triacylglycerols (TAG) were achieved at 60 degrees C (43% in 4.5 h) and 25
      degrees C (43% TAG in 7 h). The dominant species in DAG-rich products were LnL
      and LL. TAG-rich products obtained with Lipozyme RM IM had LLL and LLO/OLO as
      their predominant TAG. Quantitative conversions to DAG were obtained in 3-4.5 h
      with 10% (w/w) Lipase G 50 at 60 degrees C and a molar ratio of free CLA to
      hydroxyl groups of 5:1.

PMID- 19113873
TI  - Determination of extractability of pine bark using supercritical CO(2) extraction
      and different solvents: optimization and prediction.
AB  - Bark from Pinus brutia was extracted with supercritical fluid extraction (SFE),
      using CO(2), at various extraction conditions both at laboratory and at pilot
      scale. Optimized parameters were 200 bar, 60 degrees C, and 3% ethanol at a
      solvent/feed ratio of 30. Additionally, the pine bark was sonicated (1 h at 50
      degrees C) by different solvents (n-hexane, dichloromethane, ethyl acetate, and
      ethanol) to investigate the correlation between the different extraction setups
      and to obtain information on SFE up-scaling possibilities. Analyzed by HPLC, 7.2%
      of (-)-catechin was extractable at laboratory scale, and 58.4% (800 bar) and
      47.8% (200 bar), both with modifiers, at pilot scale. By sonication with ethanol,
      46.8% of (-)-catechin and almost 100% of (-)-epicatechin and (-)-catechin gallate
      were extracted. Ethyl acetate extract revealed high correlations with the
      laboratory scale SFE (r = 0.98) and also pilot scale SFE runs at 200 (r = 0.99)
      and 800 bar (r = 0.98) without modifiers.

PMID- 19113874
TI  - Interfacial properties of mixed beta-lactoglobulin-SDS layers at the water/air
      and water/oil interface.
AB  - The adsorption behavior of the beta-lactoglobuline has been studied in the
      presence of the anionic surfactant sodium dodecylsulfate (SDS) and compared for
      two different interfaces, water/air and water/hexane. The fitting of experimental
      data (adsorption isotherms) by a mixed adsorption model and the determination of
      structural parameters such as the molecular area occupied by the protein
      surfactant complex and the surfactant molecules at the interface allowed to have
      a better understanding of the composition and as a consequence the behavior of
      the mixed interfacial layer. The parameters obtained for the mixtures are similar
      to those obtained separately for the single components, but the comparison of the
      both interfaces has shown significant differences. Much higher concentration of
      complex is found at the water/hexane interface, which is the result of a better
      affinity of the protein for this interface. A higher penetration of the protein
      into the oil phase and the presence of interactions between protein-surfactant
      complexes and free surfactant molecules stabilize the interface preventing its
      replacement by the SDS molecules. Rheological experiments show a decrease of the
      visco-elastic modulus at both interfaces with increasing SDS concentration. But
      at the water/oil interface, contrary to the water/air interface at which the
      replacement of the protein has been clearly observed, this decrease is attributed
      to changes of complex properties. At high SDS concentrations, an increase of the
      hydrophilic character due to hydrophobic interactions with the surfactant
      molecules leads to an increase in the mobility of the complex, which favors its
      desorption upon increased competition by the surfactant.

PMID- 19113876
TI  - Pluronic L64 micelles near cloud point: investigating the role of micellar growth
      and interaction in critical concentration fluctuation and percolation.
AB  - The structure and the properties of the (Ethylene Oxide)(13)(Propylene
      Oxide)(30)(Ethylene Oxide)(13) (Pluronic L64, MW approximately 2900) micelles
      have been studied in the aqueous medium by small angle neutron scattering (SANS),
      dynamic light scattering (DLS) and viscometry measurements. The aqueous solutions
      of this triblock copolymer are unique among the pluronic solutions in showing
      critical concentration fluctuations and a concomitant enhancement in viscosity on
      approaching their cloud point. So far these results have been attributed solely
      to the presence of attractive interaction between the spherical L64 micelles.
      Recent theoretical studies, on the other hand, suggest that L64 micelles prefer a
      prolate ellipsoidal structure to sphere (Bedrov et al. Langmuir 2007, 23, 12032)
      and have a predominantly repulsive intermicellar interaction. A comparative
      analysis of our SANS data based on the spherical and prolate ellipsoidal
      structure shows that the L64 micelles can be best described by a prolate
      ellipsoidal structure, the aspect ratios of which increase progressively with
      increase in temperature. This, together with our viscosity and DLS studies,
      suggests that the enhanced viscosity of the copolymer solution near the cloud
      point arises largely due to the anisotropic growth of the micelles to the worm
      like structures. The role of the intermicellar attractive interaction has thus
      been limited to the observed critical concentration fluctuation, and its effect
      decreases progressively with increase in copolymer concentration. It has also
      been shown that the water structure making salts like NaCl reduces the micellar
      growth temperature and helps in forming worm-like micelles at the room
      temperature. These studies thus identify the effect of micellar growth and
      interaction in determining the properties of the copolymer solution near the
      cloud point, which are the first of its kind in the case of the pluronics.

PMID- 19113877
TI  - Enzymatic hemisynthesis of metabolites and conjugates of anthocyanins.
AB  - This work aims to study the phase II metabolization of anthocyanins that is
      likely to occur in vivo. Anthocyanins (delphinidin, cyanidin, and malvidin-3
      glucosides) were incubated with phase II enzymes in the presence of activated
      cofactors in order to obtain glutathionyl conjugates, methylated and
      glucuronydated compounds. Overall, the three anthocyanins tested were metabolized
      in vitro. Two compounds were detected by HPLC after incubation of human liver
      cytosolic fraction with cyanidin-3-glucoside and one compound with delphinidin-3
      glucoside. These compounds were identified as monomethylated products. LC-MS
      analysis yielded mass data that fit with the anthocyanin structures bearing an
      additional methyl group in ring B. Several compounds were detected by HPLC after
      incubation of human liver microsomes with malvidin, cyanidin, and delphinidin-3
      glucosides. These compounds were identified as monoglucuronides products after
      HPLC analysis. Conjugation with glutathione also occurred as proved by the mass
      data obtained. However, in this case, two anthocyanin equilibrium forms
      (flavylium and chalcone or water adducts) conjugated with glutathione were
      detected. Overall, the data of the present work shows the feasibility of the in
      vitro enzymatic hemisynthesis of metabolites and glutathione conjugates of
      anthocyanins. This first experimental approach may further allow the achievement
      of new purified forms of anthocyanins, some of which do not occur in nature, and
      also the determination of whether these compounds are the bioactive forms
      responsible for some of the biological activities reported for anthocyanins.

PMID- 19113878
TI  - Investigation of water structure in nafion membranes by infrared spectroscopy and
      molecular dynamics simulation.
AB  - The structure and interactions of water species in hydrated Nafion membranes as a
      function of water content were investigated on the basis of medium-infrared
      spectral analysis and molecular dynamics (MD) simulations. The spectral
      decomposition of the FT-IR data in the stretching OH region was performed on
      different levels of hydration of the sulfate functional groups (lambdaH2O/RSO3- =
      2-22). Quantum mechanical calculations of two model systems
      [perfluoroethanesulfonic acid/(H2O)6 cluster] and a [perfluorobutanesulfonic
      acid/(H2O)6 crystal] were carried out in order to account for the band
      assignments of Nafion in the stretching OH region (2500-4000 cm-1). Our findings
      indicated that the secondary structure of water species in Nafion can be
      accurately explained in terms of our reactive force field for water. The
      distinction between "surface" and "bulk" water contributions in Nafion membrane
      pores is proposed along with a quantitative estimate of the different types of OH
      groups present in the system. The average pore size was calculated and supported
      by the spectral results.

PMID- 19113880
TI  - Short-term culture of umbilical cord blood-derived CD34 cells enhances
      engraftment into NOD/SCID mice through increased CXCR4 expression.
AB  - Human umbilical cord blood (CB) has been used successfully in stem cell
      transplantation. A subpopulation of CD34(+) cells expresses chemokine receptor
      CXCR4 which is critical for bone marrow engraftment in human hematopoietic stem
      cells. Here, we demonstrate the effect of short-term culture on CXCR4 expression
      on umbilical CB-derived CD34(+) cells and subsequent engraftment capability in
      nonobese diabetic/severe combined immunodeficient (NOD/SCID) mice. Surface CXCR4
      expression on CD34(+) cells increased after incubating the cells in medium alone
      for 2 h; this effect was blocked by the addition of AMD3100. No difference in
      CXCR4 mRNA expression was noted after incubating CD34(+) cells in culture for 2
      h, although these cells showed significantly increased transmigrational activity
      toward SDF-1 and homing activity in NOD/SCID mice. Furthermore, cultured human
      CD34(+) cells showed improved engraftment into the bone marrow of NOD/SCID mice
      compared to noncultured or AMD3100-treated CD34(+) cells. These observations
      suggest that increased cell surface expression of CXCR4 on CD34(+) cells improved
      the engraftment of human umbilical CB cells into bone marrow through enhanced
      homing activity.

PMID- 19113881
TI  - Cellulose whiskers versus microfibrils: influence of the nature of the
      nanoparticle and its surface functionalization on the thermal and mechanical
      properties of nanocomposites.
AB  - In the present work, nanowhiskers and microfibrillated cellulose (MFC) both
      extracted from sisal were used to reinforce polycaprolactone (PCL). We report the
      influence of the nanoparticle's nature on the mechanical and thermal properties
      of the ensuing nanocomposites. The surface of both the nanoparticles was
      chemically modified to improve their compatibilization with the polymeric matrix.
      N-Octadecyl isocyanate (C18H37NCO) was used as the grafting agent. PCL
      nanocomposite films reinforced with sisal whiskers or MFC (raw or chemically
      modified) were prepared by film casting. The thermal behavior (Tg, Tm, Tc, and
      degree of crystallinity) and the mechanical properties of the nanocomposites in
      both the linear and the nonlinear range were determined using differential
      scanning calorimetry (DSC), dynamical mechanical analysis (DMA), and tensile
      tests, respectively. Significant differences were reported according to the
      nature of the nanoparticle and amount of nanofillers used as reinforcement. It
      was also proved that the chemical treatment clearly improves the ultimate
      properties of the nanocomposites.

PMID- 19113882
TI  - On the structure of "5-nitrosotropolone".
AB  - It has long been discussed whether "5-nitrosotropolone" 1 takes the nitroso
      structure 1A or the tautomeric oxime structure 1B. Analysis of NMR and UV spectra
      data in this study indicates that the tropoquinone-5-monoxime 1B is preferred.
      The UV absorption shift to longer wavelength at dilute solutions is attributable
      to the dissociated form 3.

PMID- 19113883
TI  - Depletion of high-abundance serum proteins from human uterine lavages enhances
      detection of lower-abundance proteins.
AB  - Two-dimentional electrophoresis, 2-DE, of human uterine lavages demonstrated the
      abundance of serum proteins. Two methods of serum protein removal were assessed.
      Multiple affinity removal system was most effective in depleting abundant serum
      proteins. 2D-DiGE comparing depleted versus nondepleted lavages resulted in
      increased protein detection following depletion, further enhanced by assessing
      the protein profile over a narrower pI 4-7 range. Demonstrating depletion of
      abundant serum proteins is important for sensitive proteomic analysis.

PMID- 19113884
TI  - Remote stereocontrol mediated by a sulfinyl group: synthesis of allylic alcohols
      via chemoselective and diastereoselective reduction of gamma-methylene delta
      ketosulfoxides.
AB  - The efficiency of the sulfinyl group as a remote controller of the
      chemoselectivity and diastereoselectivity of the reduction of alpha, beta
      unsaturated alpha-[2-(p-tolylsulfinyl)phenyl] substituted ketones 1 has been
      demonstrated in reactions carried out under NaBH4 in the presence of Yb(OTf)3 as
      the chelating agent. The starting unsaturated ketones have been prepared from the
      corresponding 2-(p-tolylsulfinyl) benzyl alkyl (and aryl) ketones 2 by insertion
      of the methylidene group under modified Mannich conditions, exploiting ultrasound
      irradiation to obtain the aminomethylation adducts and silica gel treatment to
      produce its complete elimination. Desulfinylation of the reduction products
      yielded the corresponding vinyl carbinols with high enantiomeric purity.

PMID- 19113885
TI  - Serum PEDF levels are decreased in a spontaneous animal model for human
      autoimmune uveitis.
AB  - Identification of biomarkers is of critical relevance toward improving diagnosis
      and therapy of autoimmune disorders. Serum markers are a desirable choice as sera
      are easily accessible and the development of assays for routine clinical
      detection prompts feasible. Autoimmune uveitis, a recurrent disease affecting the
      eye, is characterized by returning inflammatory attacks of the inner eye followed
      by variable periods of quiescent stages. Spontaneous equine recurrent uveitis
      (ERU) is the equine equivalent and serves as a model for the human disease. To
      identify potential biomarker candidates, we first systematically compared the
      proteomes of individual ERU cases with healthy controls by proteomic profiling
      using 2-D difference-gel-electrophoresis (2-D DIGE) followed by tandem mass
      spectrometry. A total of seven differentially expressed proteins were identified.
      Besides the upregulation of IgG and the significant lower expression of albumin,
      Antithrombin III, and Vitamin D binding protein, we found complement components
      C1q and C4, to be downregulated in uveitic state. Interestingly, Pigment
      epithelium-derived factor (PEDF), a marker already detected by 2DE differential
      proteome analysis in ERU target tissues, vitreous and retina, was found to be
      also significantly downregulated in sera. The lower expression of PEDF in sera of
      horses with uveitis could be verified in a cohort of 116 ERU cases and 115
      healthy controls. Our findings of a significant lower PEDF expression in ERU
      cases also in the periphery of the eye proves PEDF as a promising uveitis
      biomarker.

PMID- 19113886
TI  - Side chain chemistry mediates backbone fragmentation in hydrogen deficient
      peptide radicals.
AB  - A crown ether based, photolabile radical precursor which forms noncovalent
      complexes with peptides has been prepared. The peptide/precursor complexes can be
      electrosprayed, isolated in an ion trap, and then subjected to laser photolysis
      and collision induced dissociation to generate hydrogen deficient peptide
      radicals. It is demonstrated that these peptide radicals behave very differently
      from the hydrogen rich peptide radicals generated by electron capture methods. In
      fact, it is shown that side chain chemistry dictates both the occurrence and
      relative abundance of backbone fragments that are observed. Fragmentation at
      aromatic residues occurs preferentially over most other amino acids. The origin
      of this selectivity relates to the mechanism by which backbone dissociation is
      initiated. The first step is abstraction of a beta-hydrogen from the side chain,
      followed by beta-elimination to yield primarily a-type fragment ions.
      Calculations reveal that those side chains which can easily lose a beta-hydrogen
      correlate well with experimentally favored sites for backbone fragmentation. In
      addition, radical mediated side chain losses from the parent peptide are
      frequently observed. Eleven amino acids exhibit unique mass losses from side
      chains which positively identify that particular amino acid as part of the parent
      peptide. Therefore, side chain losses allow one to unambiguously narrow the
      possible sequences for a parent peptide, which when combined with predictable
      backbone fragmentation should lead to greatly increased confidence in peptide
      identification.

PMID- 19113887
TI  - Influences of periodic mechanical deformation on spiral breakup in excitable
      media.
AB  - Influences of periodic mechanical deformation (PMD) on spiral breakup that
      results from Doppler instability in excitable media are investigated. We present
      a new effect: a high degree of homogeneous PMD is favored to prevent the low
      excitability-induced breakup of spiral waves. The frequency and amplitude of PMD
      are also significant for achieving this purpose. The underlying mechanism of
      successful control is also discussed, which is believed to be related to the
      increase of the minimum temporal period of the meandering spiral when the
      suitable PMD is applied.

PMID- 19113888
TI  - Nanosecond time-dependent Stokes shift at the tunnel mouth of haloalkane
      dehalogenases.
AB  - The tunnel mouths are evolutionally the most variable regions in the structures
      of haloalkane dehalogenases originating from different bacterial species,
      suggesting their importance for adaptation of enzymes to various substrates. We
      decided to monitor the dynamics of this particular region by means of time
      resolved fluorescence spectroscopy and molecular dynamic simulations. To label
      the enzyme specifically, we adapted a novel procedure that utilizes a coumarin
      dye containing a halide-hydrocarbon linker, which serves as a substrate for
      enzymatic reaction. The procedure leads to a coumarin dye covalently attached and
      specifically located in the tunnel mouth of the enzyme. In this manner, we
      stained two haloalkane dehalogenase mutants, DbjA-H280F and DhaA-H272F. The
      measurements of time-resolved fluorescence anisotropy, acrylamide quenching, and
      time-resolved emission spectra reveal differences in the polarity, accessibility
      and mobility of the dye and its microenvironment for both of the mutants. The
      obtained experimental data are consistent with the results obtained by molecular
      dynamics calculations and correlate with the anatomy of the tunnel mouths, which
      were proposed to have a strong impact on the catalytic activity and specificity
      of the examined mutants. Interestingly, the kinetics of the recorded time
      dependent Stokes shift is unusual slow; it occurs on the nanosecond time-scale,
      suggesting that the protein dynamics is extremely slowed down at the region
      involved in the exchange of ligands between the active-site cavity and bulk
      solvent.

PMID- 19113889
TI  - Magnetic tunnel junctions with ferroelectric barriers: prediction of four
      resistance States from first principles.
AB  - Magnetic tunnel junctions (MTJs), composed of two ferromagnetic electrodes
      separated by a thin insulating barrier layer, are currently used in spintronic
      devices, such as magnetic sensors and magnetic random access memories. Recently,
      driven by demonstrations of ferroelectricity at the nanoscale, thin-film
      ferroelectric barriers were proposed to extend the functionality of MTJs. Due to
      the sensitivity of conductance to the magnetization alignment of the electrodes
      (tunneling magnetoresistance) and the polarization orientation in the
      ferroelectric barrier (tunneling electroresistance), these multiferroic tunnel
      junctions (MFTJs) may serve as four-state resistance devices. On the basis of
      first-principles calculations, we demonstrate four resistance states in
      SrRuO(3)/BaTiO(3)/SrRuO(3) MFTJs with asymmetric interfaces. We find that the
      resistance of such a MFTJ is significantly changed when the electric polarization
      of the barrier is reversed and/or when the magnetizations of the electrodes are
      switched from parallel to antiparallel. These results reveal the exciting
      prospects of MFTJs for application as multifunctional spintronic devices.

PMID- 19113890
TI  - Design of a pH-dependent molecular switch in a caged protein platform.
AB  - Self-assembling protein cages provide a wide range of possible applications in
      nanotechnology. We report the first example of an engineered pH-dependent
      molecular switch in a virus-like particle. By genetically manipulating the
      subunit-subunit interface of the E2 subunit of pyruvate dehydrogenase, we
      introduce pH-responsive assembly into a scaffold that is natively stable at both
      pH 5.0 and 7.4. The redesigned protein module yields an intact, stable particle
      at pH 7.4 that dissociates at pH 5.0. This triggered behavior is especially
      relevant for applications in therapeutic delivery.

PMID- 19113891
TI  - Programmable resistance switching in nanoscale two-terminal devices.
AB  - We show that in nanoscale two-terminal resistive switches the resistance
      switching can be dominated by the formation of a single conductive filament. The
      probabilistic filament formation process strongly affects the device operation
      principle, and can be programmed to facilitate new functionalities such as
      multibit switching with partially formed filaments. In addition, the nanoscale
      switches exhibit excellent performance metrics making them well suited for memory
      or logic operations using conventional or emerging hybrid nano/CMOS
      architectures.

PMID- 19113892
TI  - A novel approach to create a highly ordered monolayer film of graphene nanosheets
      at the liquid-liquid interface.
AB  - A monolayer of ultrathin sheets of highly hydrophobic graphene nanosheets was
      prepared on a large area substrate via self-assembly at the liquid-liquid
      interface. Driven by the minimization of interfacial energy these planar shaped
      graphene nanosheets produce a close packed monolayer structure at the liquid
      liquid interface. This monolayer film shows high electrical conductivity of more
      than 1000 S/cm and an optical transmission of more than 70% at a wavelength of
      550 nm. Interfacial self-assembly of these nanosheets demonstrates a promising
      route for the application of this novel material in optoelectronics applications.

PMID- 19113893
TI  - Self-assembled metallic nanowires on a dielectric support: Pd on rutile
      TiO2(110).
AB  - Palladium nanoparticles supported on rutile TiO(2)(110)-1 x 1 have been studied
      using the complementary techniques of scanning tunneling microscopy and X-ray
      photoemission electron microscopy. Two distinct types of palladium nanoparticles
      are observed, namely long nanowires up to 1000 nm long, and smaller dotlike
      features with diameters ranging from 80-160 nm. X-ray photoemission electron
      microscopy reveals that the nanoparticles are composed of metallic palladium,
      separated by the bare TiO(2)(110) surface.

PMID- 19113894
TI  - Myxotyrosides A and B, Unusual rhamnosides from Myxococcus sp.
AB  - Myxobacteria are gliding bacteria of the delta-subdivision of the Proteobacteria
      and known for their unique biosynthetic capabilities. Two examples of a new class
      of metabolites, myxotyrosides A (1) and B (2), were isolated from a Myxococcus
      sp. The myxotyrosides have a tyrosine-derived core structure glycosylated with
      rhamnose and acylated with unusual fatty acids such as (Z)-15-methyl-2
      hexadecenoic and (Z)-2-hexadecenoic acid. The fatty acid profile of the
      investigated Myxococcus sp. (strain 131) is that of a typical myxobacterium with
      a high similarity to those described for M. fulvus and M. xanthus, with
      significant concentrations of neither 15-methyl-2-hexadecenoic acid nor 2
      hexadecenoic acid being detected.

PMID- 19113895
TI  - Retention of configuration in photolytic decarboxylation of peresters to form
      chiral acetals and ethers.
AB  - Peresters generate ethers in good yields when photolyzed in the absence of
      solvent using short wavelength UV light. At -78 degrees C or below, the process
      proceeds predominantly with retention of configuration at the site adjacent to
      the carbonyl where the decarboxylation occurs, but increase in temperature
      results in loss of stereochemical control. Chiral acyclic acetals can be prepared
      using precursors derived from tartaric or malic acids.

PMID- 19113898
TI  - The p-bromodienone route to nucleophilic functionalization of calixarene exo rim.
AB  - Easily accessible calixarene p-bromodienone derivatives undergo a silver-mediated
      nucleophilic substitution and a subsequent rearomatization with a range of
      different O-nucleophiles (alcohols and carboxylates) to give p-alkoxy- or p
      acyloxycalixarenes in workable yields. This approach can be considered a general
      "p-bromodienone route" to functionalize calixarene exo rim with nucleophiles.

PMID- 19113896
TI  - Substitution on the A-ring confers to bryopyran analogues the unique biological
      activity characteristic of bryostatins and distinct from that of the phorbol
      esters.
AB  - A close structural analogue of bryostatin 1, which differs from bryostatin 1 only
      by the absence of the C(30) carbomethoxy group (on the C(13) enoate of the B
      ring), has been prepared by total synthesis. Biological assays reveal a crucial
      role for substitution in the bryostatin 1 A-ring in conferring those responses
      which are characteristic of bryostatin 1 and distinct from those observed with
      PMA.

PMID- 19113897
TI  - Identification and characterization of side population cells in embryonic stem
      cell cultures.
AB  - Marker and functional heterogeneity has been described for embryonic stem cells
      (ESCs). This property has been correlated with the presence of ESC subpopulations
      resembling pluripotent cell lineages of the embryo. The ability to efflux Hoechst
      (Ho) displayed by side population (SP) cells has proven valuable as a marker to
      identify multipotent stem cells from a variety of tissues. Here we report that
      cultures from different ESC lines consistently show an SP population that
      displays antigens of undifferentiated ESCs, distinct drug efflux properties, and
      an expression pattern of ABC transporters, inner cell mass (ICM), and epiblast
      genes, which distinguish it from the non-SP ESC fraction. This SP population
      contains pluripotent cells that differentiate into ectoderm, mesoderm, and
      endoderm in embryoid body and teratoma assays. Further, purified SP cells
      efficiently integrate into developing morulae and contribute to ICM. Under
      standard ESC culture conditions, SP and non-SP populations display ability to
      convert into each other; however, an equilibrium establishes between these
      fractions. Using protocols customized for SP ESCs, we report that cells with
      similar efflux properties can be identified in the ICM of peri-implanted
      blastocysts. Our results indicate that ESCs display heterogeneity for the SP
      marker, and the SP population of these cultures contains cells that
      phenotypically and functionally resemble efflux-active ICM cells of the peri
      implanted embryo. Our observations suggest an involvement of the SP phenotype in
      ESC maintenance and early embryo development, and support the idea that ESCs are
      composed of distinct phenotypic and functional pluripotent subpopulations in
      dynamic equilibrium.

PMID- 19113900
TI  - Total synthesis of pseudodehydrothyrsiferol.
AB  - An enantioselective total synthesis of pseudodehydrothyrsiferol has been
      accomplished. The synthetic sequence highlights formation of the highly strained
      tetrahydropyran C-ring by a Mitsunobu-type S(N)2 reaction with an oxygen
      nucleophile.

PMID- 19113901
TI  - The acid hydrolysis mechanism of acetals catalyzed by a supramolecular assembly
      in basic solution.
AB  - A self-assembled supramolecular host catalyzes the hydrolysis of acetals in basic
      aqueous solution. The mechanism of hydrolysis is consistent with the Michaelis
      Menten kinetic model. Further investigation of the rate-limiting step of the
      reaction revealed a negative entropy of activation (DeltaS(double dagger) = -9
      cal mol(-1) K(-1)) and an inverse solvent isotope effect (k(H(2)O)/k(D(2)O) =
      0.62). These data suggest that the mechanism of hydrolysis that takes place
      inside the assembly proceeds through an A-2 mechanism, in contrast to the A-1
      mechanism operating in the uncatalyzed reaction. Comparison of the rates of
      acetal hydrolysis in the assembly with the rate of the reaction of unencapsulated
      substrates reveals rate accelerations of up to 980 over the background reaction
      for the substrate 1,1-diethoxyethane.

PMID- 19113902
TI  - Stereoselective synthesis of bishomo-inositols as glycosidase inhibitors.
AB  - For the synthesis of various bishomo-inositol derivatives, 1,3,3a,7a-tetrahydro-2
      benzofuran was used as the key compound. For further functionalization of the
      diene unit, the diene was subjected to photooxygenation, epoxidation, and cis
      hydroxylation reactions. The endoperoxide linkage was cleaved by thiourea. The
      remaining double bond was subjected to epoxidation and cis-hydroxylation
      reactions. The epoxide rings and tetrahydrofuran rings formed were opened by acid
      catalyzed reaction with sulfamic acid. The combination of these reactions
      resulted in the formation of various new inositol derivatives such as bishomo
      chiro-inositol, bishomo-myo-inositol, and two isomeric bishomo-allo-inositols.

PMID- 19113903
TI  - Development of an enzyme-linked immunosorbent assay for determination of the
      miticide bromopropylate.
AB  - This paper reports for the first time the development of an immunoassay for the
      analysis of the miticide bromopropylate (BP). The chemical structure of the
      immunizing haptens was designed to maximize the recognition of the bis
      bromophenyl group of BP. Thus, the assay uses polyclonal antibodies raised
      against 2,2-bis(4-bromophenyl)-N-2-hydroxyacetamide-butanoic acid (hapten 2)
      conjugated to keyhole limpet hemocyanin from horseshoe crab. A heterologous
      indirect competitive enzyme-linked immunosorbent assay (ELISA) has been developed
      that can detect BP down to 0.14 microg L(-1). The assay has been proven to
      tolerate a wide range of ionic strengths and pH values. Studies on the
      selectivity of this immunoassay have demonstrated a high recognition of related
      pesticides that contain a bis-halophenyl group in their structure. Other
      pesticides do not interfere in the analysis of BP using this immunochemical
      technique. Preliminary experiments have shown that BP can be directly analyzed in
      white wine samples down to 0.16 microg L(-1) without the necessity of a cleanup
      procedure prior to the ELISA.

PMID- 19113904
TI  - Diastereoselective synthesis of beta-substituted-alpha,gamma-diaminobutyric acids
      and pyrrolidines containing multichiral centers.
AB  - A convenient and efficient way for the highly diastereoselective synthesis of
      beta-substituted-alpha,gamma-diaminobutyric acids and pyrrolidines containing
      multichiral centers has been well-developed. Michael addition of chiral tricyclic
      iminolactones 1 and 2 to nitroalkenes afforded the adducts in good yields (up to
      95%) and excellent diastereoselectivities (up to dr > 99:1) when titanium(IV)
      isopropoxide was used. Configuration of the second new stereocenter was decided
      by the substitution of nitroalkene. Selective reduction and hydrolysis of the
      Michael adducts furnished the desired beta-substituted-alpha,gamma-diaminobutyric
      acids in good yields and high enantiomeric excesses (>99% ee). Synthesis of
      pyrrolidines containing multichiral centers has also been accomplished in good to
      excellent yields and diastereoselectivities under mild conditions via Michael
      Mannich tandem reactions using Cu(OTf)(2) or AgOTf as an activating reagent for
      aliphatic nitroalkenes.

PMID- 19113906
TI  - Lipid levels: a link between cardiovascular disease and osteoporosis?
AB  - Epidemiological observations support a positive relationship between
      cardiovascular diseases (CVD) and osteoporosis, where cholesterol has been
      indicated to be a possible link. Only a few studies have investigated the
      relation between lipids and BMD, but the association remains unclear. We studied
      the relationship between serum lipids and BMD of the calcaneus. A cross-sectional
      population-based study was performed, based on data from the Longitudinal Aging
      Study Amsterdam, including 620 men and 635 women, 65-88 yr of age. BMD was
      measured by quantitative ultrasound (QUS), velocity of sound (VOS; m/s), and
      broadband ultrasound attenuation (BUA; dB/MHz). Models were adjusted for age,
      body mass index, physical activity, smoking, alcohol, diabetes mellitus,
      hypertension, testosterone, and 25-hydroxyvitamin D. No association was found
      between total cholesterol (TC) and QUS. Men and women in the highest quartile of
      high-density lipoprotein cholesterol (HDL-c) had a significantly lower QUS (men
      VOS: beta = -20.8, p = 0.00; BUA: beta = -5.2, p = 0.02; women-VOS: beta = -18.6,
      p = 0.00) compared with men and women in the lowest quartile. An even stronger
      positive association was seen between TC/HDL-c ratio and QUS (men-VOS: beta =
      21.8, p = 0.00; BUA: beta = 5.5, p = 0.01; women-VOS: beta = 19.2, p = 0.00; BUA:
      beta = 3.6, p = 0.05). Our analysis shows that the lipid profile that is
      favorable in the prevention of CVD (i.e., high levels of HDL-c and low TC/HDL-c
      ratio) is unfavorable for QUS. These results indicate that HDL-c levels do not
      explain the association between osteoporosis and CVD.

PMID- 19113907
TI  - Beta-adrenergic blockade and leptin replacement effectively mitigate disuse bone
      loss.
AB  - Our objective was to test effects of beta-adrenergic blockade on hindlimb
      unloading (HU)-induced bone loss and serum leptin and to compare these responses
      with those observed with leptin replacement. Adult male rats were randomized into
      six groups (n = 10 each): HU rats treated with vehicle (VEHHU), leptin analog
      (LEPHU), or beta-blocker (BBHU) during a 28-day HU and cage activity controls
      (CC) treated with the same three agents and pair-fed to HU rats. On days 0 and
      28, pQCT scans of proximal tibia and serum collections for leptin assays were
      performed, and histomorphometric measures of proximal tibia cancellous bone were
      assessed. The 20% decrease in cancellous vBMD observed in the VEHHU group was
      halved in BBHU rats and LEPHU rats. Bone formation rate (BFR) in BBHU rats, but
      not in LEPHU rats, was preserved. The 3-fold increase in resorption surface with
      HU was abolished by BB and LEP treatments. The decrease in serum leptin after a
      28-day HU was attenuated in BBHU and LEPHU rats and was predictive of the
      decrease in BFR with HU. Blocking sympathetic adrenergic signaling by peripheral
      administration of a beta-blocker during HU mitigates disuse-induced decreases in
      cancellous bone mass through stimulation of osteoblastic activity and suppression
      of osteoclastic activity. A direct effect of beta-adrenergic blockade on bone
      cells during HU may be enhanced by an indirect effect mitigating reductions in
      circulating leptin, possibly through disinhibition of leptin release from
      adipocytes.

PMID- 19113909
TI  - BMD in population-based adult women is associated with socioeconomic status.
AB  - With few exceptions, an inverse relationship exists between social disadvantage
      and disease. However, there are conflicting data for the relationship between
      socioeconomic status (SES) and BMD. The aim of this study was to assess the
      association between SES and lifestyle exposures in relation to BMD. In a cross
      sectional study conducted using 1494 randomly selected population-based adult
      women, we assessed the association between SES and lifestyle exposures in
      relation to BMD. BMD was measured at multiple anatomical sites by DXA. SES was
      determined by cross-referencing residential addresses with Australian Bureau of
      Statistics 1996 census data for the study region and categorized in quintiles.
      Lifestyle variables were collected by self-report. Regression models used to
      assess the relationship between SES and BMD were adjusted for age, height,
      weight, dietary calcium, smoking, alcohol consumption, physical activity, hormone
      therapy, and calcium/vitamin D supplements. Unadjusted BMD differed across SES
      quintiles (p < 0.05). At each skeletal site and SES index, a consistent peak in
      adjusted BMD was observed in the mid-quintiles. Differences in adjusted BMD were
      observed between SES quintiles 1 and 4 (3-7%) and between quintiles 5 and 4 (2
      7%). At the spine, the maximum difference was observed (7.5%). In a subset of
      women, serum 25(OH)D explained a proportion of the association between SES and
      BMD (difference remained up to 4.2%). Observed differences in BMD across SES
      quintiles, consistent across both SES indices, suggest that low BMD may be
      evident for both the most disadvantaged and most advantaged.

PMID- 19113908
TI  - ECM compliance regulates osteogenesis by influencing MAPK signaling downstream of
      RhoA and ROCK.
AB  - The compliance of the extracellular matrix (ECM) regulates osteogenic
      differentiation by modulating extracellular signal-regulated kinase (ERK)
      activity. However, the molecular mechanism linking ECM compliance to the ERK
      mitogen-activated protein kinase (MAPK) pathway remains unclear. Furthermore,
      RhoA has been widely implicated in integrin-mediated signaling and
      mechanotransduction. We studied the relationship between RhoA and ERK-MAPK
      signaling to determine their roles in the regulation of osteogenesis by ECM
      compliance. Inhibition of RhoA and ROCK in MC3T3-E1 pre-osteoblasts cultured on
      substrates of varying compliance reduced ERK activity, whereas constitutively
      active RhoA enhanced it. The expression of RUNX2, a potent osteogenic
      transcription factor, was increased on stiffer matrices and correlated with
      elevated ERK activity. Inhibition of RhoA, ROCK, or the MAPK pathway diminished
      RUNX2 activity and delayed the onset of osteogenesis as shown by altered
      osteocalcin (OCN) and bone sialoprotein (BSP) gene expression, alkaline
      phosphatase (ALP) activity, and matrix mineralization. These data establish that
      one possible mechanism by which ECM rigidity regulates osteogenic differentiation
      involves MAPK activation downstream of the RhoA-ROCK signaling pathway.

PMID- 19113910
TI  - Hypercalcemia and overexpression of CYP27B1 in a patient with nephrogenic
      systemic fibrosis: clinical vignette and literature review.
AB  - Nephrogenic systemic fibrosis (NSF) is a disease of thickened, hard,
      hyperpigmented skin lesions with or without systemic fibrosis occurring in
      patients with renal insufficiency and associated with the administration of
      gadolinium-containing contrast. The pathogenesis of this disease is unclear, and
      there is no definitive treatment. We describe a 71-yr-old patient with stable
      chronic lymphocytic leukemia (CLL), end-stage renal disease (ESRD), and NSF who
      presented with hypercalcemia in 2006. Before onset of renal insufficiency in
      2002, serum calcium, phosphorus, and PTH levels were normal. In 2004, the patient
      began hemodialysis, and he was diagnosed with NSF in 2005, shortly after
      undergoing an MRI with gadolinium contrast administration. Over the next 6 mo,
      albumin-corrected serum total calcium levels rose from 9.9 to 13.1 mg/dl (normal
      range, 8.5-10.5 mg/dl) with normal serum phosphorus levels. On admission in
      September 2006, 1,25-dihydroxyvitamin D [1,25(OH)(2)D] levels were elevated at
      130.7 pg/ml (normal range, 25.1-66.1 pg/ml). Biopsy of an NSF lesion showed
      increased 25-hydroxyvitamin D(3)-1-alpha hydroxylase (CYP27B1) immunostaining
      compared with the biopsy from a normal control. This is the first reported
      association of NSF with hypercalcemia caused by elevated 1,25(OH)(2)D levels.
      This metabolic disturbance should be sought in future cases to determine a
      connection between NSF, 1,25(OH)(2)D metabolism, and CYP27B1 activation in the
      skin, which may shed light on the pathogenesis of this unusual local and systemic
      fibrosing disorder.

PMID- 19113911
TI  - Dietary calcium and serum 25-hydroxyvitamin D status in relation to BMD among
      U.S. adults.
AB  - A higher calcium intake is still the primary recommendation for the prevention of
      osteoporosis, whereas vitamin D deficiency is often not addressed. To study the
      relative importance of dietary calcium intake and serum 25-hydroxyvitamin D
      [25(OH)D] status in regard to hip BMD, 4958 community-dwelling women and 5003 men
      >/=20 yr of age from the U.S. NHANES III population-based survey were studied.
      Calcium supplement users and individuals with a prior radius or hip fracture were
      excluded. We calculated standardized means for BMD by quartiles of sex-specific
      calcium intake for three 25(OH)D categories (<50, 50-74, and 75+ nM) among men
      and women, separately controlling for other important predictors of BMD. A higher
      calcium intake was significantly associated with higher BMD (p value for trend: p
      = 0.005) only for women with 25(OH)D status <50 nM, whereas calcium intake beyond
      the upper end of the lowest quartile (>566 mg/d) was not significantly associated
      with BMD at 25(OH)D concentrations >50 nM. Among men, there was no significant
      association between a higher calcium intake beyond the upper end of the lowest
      quartile (626 mg/d) and BMD within all 25(OH)D categories. Among both sexes, BMD
      increased stepwise and significantly with higher 25(OH)D concentrations (<50, 50
      74, 75+ nM; p value for trend: women < 0.0001; men = 0.0001). Among men and
      women, 25(OH)D status seems to be the dominant predictor of BMD relative to
      calcium intake. Only women with 25(OH)D concentrations <50 nM seem to benefit
      from a higher calcium intake.

PMID- 19113912
TI  - Serum estradiol is associated with volumetric BMD and modulates the impact of
      physical activity on bone size at the age of peak bone mass: a study in healthy
      male siblings.
AB  - This study investigates determinants of peak bone mass (PBM) in healthy men,
      focusing on effects and interactions of parameters reflecting mechanical loading
      and sex steroids. Healthy male siblings (n = 677; 25-45 yr) were recruited in a
      cross-sectional, population-based study. Physical activity score was assessed by
      a self-reported questionnaire. Cross-sectional muscle area (CSMA) and bone
      parameters of radius (4% and 66% site) and tibia (66% site) were assessed using
      pQCT. Peak torque of biceps and quadriceps muscles was assessed by isokinetic
      dynamometry. Serum testosterone (T) and estradiol (E(2)) levels were measured
      using immunoassays; free hormone fractions were calculated. Relations between
      indices of bone strength, CSMA, muscle strength, and sex steroids were studied
      using linear mixed-effects modeling. Physical activity, CSMA, and muscle strength
      were positively associated with indices of bone strength, except for volumetric
      BMD (vBMD). After controlling for age, weight, and height, free E(2) levels were
      positively associated with trabecular and cortical vBMD, negatively associated
      with endosteal circumference at the radius, and positively associated with
      cortical vBMD at the tibia. In addition, positive interactions between physical
      activity and serum E(2) concentrations were observed for bone size at the tibia.
      No associations between free T levels and pQCT bone parameters were found. In
      this population of healthy men at the age of PBM, parameters reflecting
      mechanical loading are confirmed as important determinants of bone size. E(2),
      but not T, levels are positively associated with vBMD and modulate the impact of
      physical activity on bone size at the tibia.

PMID- 19113913
TI  - Inbred strain-specific response to biglycan deficiency in the cortical bone of
      C57BL6/129 and C3H/He mice.
AB  - Inbred strain-specific differences in mice exist in bone cross-sectional
      geometry, mechanical properties, and indices of bone formation. Inbred strain
      specific responses to external stimuli also exist, but the role of background
      strain in response to genetic deletion is not fully understood. Biglycan (bgn)
      deficiency impacts bone through negative regulation of osteoblasts, resulting in
      extracellular matrix alterations and decreased mechanical properties. Because
      osteoblasts from C3H/He (C3H) mice are inherently more active versus osteoblasts
      from other inbred strains, and the bones of C3H mice are less responsive to other
      insults, it was hypothesized that C3H mice would be relatively more resistant to
      changes associated with bgn deficiency compared with C57BL6/129 (B6;129) mice.
      Changes in mRNA expression, tissue composition, mineral density, bone formation
      rate, cross-sectional geometry, and mechanical properties were studied at 8 and
      11 wk of age in the tibias of male wildtype and bgn-deficient mice bred on B6;129
      and C3H background strains. Bgn deficiency altered collagen cross-linking and
      gene expression and the amount and composition of mineral in vivo. In bgn's
      absence, changes in collagen were independent of mouse strain. Bgn-deficiency
      increased the amount of mineral in both strains, but changes in mineral
      composition, cross-sectional geometry, and mechanical properties were dependent
      on genetic background. Bgn deficiency influenced the amount and composition of
      bone in mice from both strains at 8 wk, but C3H mice were better able to maintain
      properties close to wildtype (WT) levels. By 11 wk, most properties from C3H
      knockout (KO) bones were equal to or greater than WT levels, whereas phenotypic
      differences persisted in B6;129 KO mice. This is the first study into mouse
      strain-specific changes in a small leucine-rich proteoglycan gene disruption
      model in properties across the bone hierarchy and is also one of the first to
      relate these changes to mechanical competence. This study supports the importance
      of genetic factors in determining the response to a gene deletion and defines
      biglycan's importance to collagen and mineral composition in vivo.

PMID- 19113914
TI  - SOX9 directly binds CREB as a novel synergism with the PKA pathway in BMP-2
      induced osteochondrogenic differentiation.
AB  - SOX9 acts as a master transcription factor in osteochondrogenesis, and the
      phosphorylation by protein kinase A (PKA) has been shown to increase its DNA
      binding and transactivation activity. The PKA pathway is involved in the complex
      downstream signaling underlying the BMP-2-mediated osteochondrogenesis. This
      study therefore aimed at further analyzing the possible cross-talk between the
      SOX9 and the PKA regulation on the background of BMP-2 stimulation. It was first
      shown that the removal of the residues serine 64 and 211 of SOX9 diminished, but
      did not completely deplete, its stimulatory effect on the expression of both
      osteo- and chondrogenic markers. PKA activators and inhibitors increased and
      decreased the action of wildtype and mutated SOX9, respectively. Interestingly,
      the interplay of the SOX9 action with the PKA pathway was further shown to occur
      through direct physical association between SOX9 and CREB, a prototypical PKA
      downstream transcription factor. Moreover, the binding was shown to be an active
      biological event happening on BMP-2 stimulation. The C-terminal domain of SOX9
      and amino acid residue serine at position 133 of CREB were identified to be
      involved in the interaction. The action of SOX9 was enhanced by overexpressing
      CREB. These results suggest that PKA signaling synergizes with SOX9 at the
      nuclear and cytoplasmic levels to promote BMP-2-induced osteochondrogenic
      differentiation.

PMID- 19113915
TI  - Beta-Arrestin2 regulates RANKL and ephrins gene expression in response to bone
      remodeling in mice.
AB  - PTH-stimulated intracellular signaling is regulated by the cytoplasmic adaptor
      molecule beta-arrestin. We reported that the response of cancellous bone to
      intermittent PTH is reduced in beta-arrestin2(-/-) mice and suggested that beta
      arrestins could influence the bone mineral balance by controlling RANKL and
      osteoprotegerin (OPG) gene expression. Here, we study the role of beta-arrestin2
      on the in vitro development and activity of bone marrow (BM) osteoclasts (OCs)
      and Ephrins ligand (Efn), and receptor (Eph) mRNA levels in bone in response to
      PTH and the changes of bone microarchitecture in wildtype (WT) and beta
      arrestin2(-/-) mice in models of bone remodeling: a low calcium diet (LoCa) and
      ovariectomy (OVX). The number of PTH-stimulated OCs was higher in BM cultures
      from beta-arrestin2(-/-) compared with WT, because of a higher RANKL/OPG mRNA and
      protein ratio, without directly influencing osteoclast activity. In vivo, high
      PTH levels induced by LoCa led to greater changes in TRACP5b levels in beta
      arrestin2(-/-) compared with WT. LoCa caused a loss of BMD and bone
      microarchitecture, which was most prominent in beta-arrestin2(-/-). PTH
      downregulated Efn and Eph genes in beta-arrestin2(-/-), but not WT. After OVX,
      vertebral trabecular bone volume fraction and trabecular number were lower in
      beta-arrestin2(-/-) compared with WT. Histomorphometry showed that OC number was
      higher in OVX-beta-arrestin2(-/-) compared with WT. These results indicate that
      beta-arrestin2 inhibits osteoclastogenesis in vitro, which resulted in decreased
      bone resorption in vivo by regulating RANKL/OPG production and ephrins mRNAs. As
      such, beta-arrestins should be considered an important mechanism for the control
      of bone remodeling in response to PTH and estrogen deprivation.

PMID- 19113916
TI  - Bone structure at the distal radius during adolescent growth.
AB  - The incidence of distal forearm fractures peaks during the adolescent growth
      spurt, but the structural basis for this is unclear. Thus, we studied healthy 6-
      to 21-yr-old girls (n = 66) and boys (n = 61) using high-resolution pQCT (voxel
      size, 82 microm) at the distal radius. Subjects were classified into five groups
      by bone-age: group I (prepuberty, 6-8 yr), group II (early puberty, 9-11 yr),
      group III (midpuberty, 12-14 yr), group IV (late puberty, 15-17 yr), and group V
      (postpuberty, 18-21 yr). Compared with group I, trabecular parameters (bone
      volume fraction, trabecular number, and thickness) did not change in girls but
      increased in boys from late puberty onward. Cortical thickness and density
      decreased from pre- to midpuberty in girls but were unchanged in boys, before
      rising to higher levels at the end of puberty in both sexes. Total bone strength,
      assessed using microfinite element models, increased linearly across bone age
      groups in both sexes, with boys showing greater bone strength than girls after
      midpuberty. The proportion of load borne by cortical bone, and the ratio of
      cortical to trabecular bone volume, decreased transiently during mid- to late
      puberty in both sexes, with apparent cortical porosity peaking during this time.
      This mirrors the incidence of distal forearm fractures in prior studies. We
      conclude that regional deficits in cortical bone may underlie the adolescent peak
      in forearm fractures. Whether these deficits are more severe in children who
      sustain forearm fractures or persist into later life warrants further study.

PMID- 19113917
TI  - Alendronate treatment of the brtl osteogenesis imperfecta mouse improves femoral
      geometry and load response before fracture but decreases predicted material
      properties and has detrimental effects on osteoblasts and bone formation.
AB  - Long courses of bisphosphonates are widely administered to children with
      osteogenesis imperfecta (OI), although bisphosphonates do not block mutant
      collagen secretion and may affect bone matrix composition or structure. The Brtl
      mouse has a glycine substitution in col1a1 and is ideal for modeling the effects
      of bisphosphonate in classical OI. We treated Brtl and wildtype mice with
      alendronate (Aln; 0.219 mg/kg/wk, SC) for 6 or 12 wk and compared treated and
      untreated femora of both genotypes. Mutant and wildtype bone had similar
      responses to Aln treatment. Femoral areal BMD and cortical volumetric BMD
      increased significantly after 12 wk, but femoral length and growth curves were
      unaltered. Aln improved Brtl diaphyseal cortical thickness and trabecular number
      after 6 wk and cross-sectional shape after 12 wk. Mechanically, Aln significantly
      increased stiffness in wildtype femora and load to fracture in both genotypes
      after 12 wk. However, predicted material strength and elastic modulus were
      negatively impacted by 12 wk of Aln in both genotypes, and metaphyseal remnants
      of mineralized cartilage also increased. Brtl femoral brittleness was unimproved.
      Brtl osteoclast and osteoblast surface were unchanged by treatment. However,
      decreased mineral apposition rate and bone formation rate/bone surface and the
      flattened morphology of Brtl osteoblasts suggested that Aln impaired osteoblast
      function and matrix synthesis. We conclude that Aln treatment improves Brtl
      femoral geometry and load to fracture but decreases bone matrix synthesis and
      predicted material modulus and strength, with striking retention of mineralized
      cartilage. Beneficial and detrimental changes appear concomitantly. Limiting
      cumulative bisphosphonate exposure of OI bone will minimize detrimental effects.

PMID- 19113918
TI  - Vertebral fracture risk is reduced in women who lose femoral neck BMD with
      teriparatide treatment.
AB  - Response to osteoporosis therapy is often assessed by serial BMD testing.
      Patients who lose BMD without secondary causes of bone loss may be considered to
      be "nonresponders" to treatment. We examined vertebral fracture (VF) risk, change
      in lumbar spine (LS) BMD, and change in amino-terminal extension peptide of
      procollagen type I (PINP) in postmenopausal women whose femoral neck (FN) BMD
      decreased, increased, or was unchanged after receiving teriparatide (TPTD) or
      placebo (PL) in the Fracture Prevention Trial. FN and LS BMD were measured at
      baseline and 12 mo. VFs were assessed by lateral spine radiographs at baseline
      and study endpoint. A BMD change from baseline of >4% was considered to be
      clinically significant. Decreases of >4% FN BMD were less common in women
      receiving TPTD (10%) versus PL (16%, p < 0.05), yet women on TPTD who lost FN BMD
      still had significant reductions in VF risk compared with PL (RR = 0.11; 95% CI =
      0.03-0.45). VF risk reduction with TPTD compared with PL was similar across
      categories of FN BMD change from baseline at 12 mo (loss >4%, loss 0-4%, gain 0
      4%, or gain >4%; interaction p = 0.40). Irrespective of FN BMD loss or gain, TPTD
      treated women had statistically significant increases in LS BMD and PINP compared
      with PL. In both groups, losses or gains in FN BMD at 12 mo corresponded to
      losses or gains in BMC rather than changes in bone area. In conclusion, loss of
      FN BMD at 12 mo in postmenopausal women with osteoporosis treated with TPTD is
      nevertheless consistent with a good treatment response in terms of VF risk
      reduction.

PMID- 19113920
TI  - Restoration of bone mass and strength in glucocorticoid-treated mice by systemic
      transplantation of CXCR4 and cbfa-1 co-expressing mesenchymal stem cells.
AB  - Transplantation of gene-modified mesenchymal stem cells (MSCs) in animals for
      bone regeneration therapy has been evaluated extensively in recent years.
      However, increased endosteal bone formation by intravenous injection of MSCs
      ectopically expressing a foreign gene has not yet been shown. Aside from the
      clearance by lung and other tissues, the surface compositions of MSCs may not
      favor their bone marrow (BM) migration and engraftment. To overcome these
      hurdles, a gene encoding the chemokine receptor largely responsible for stromal
      derived factor-1 (SDF-1)-mediated BM homing and engraftment of hematopoietic stem
      cells (HSCs), CXCR4, was transduced into mouse C3H10T1/2 cells by adenovirus
      infection. A dose-dependent increase of CXCR4 surface expression with a parallel
      enhanced chemotaxis toward SDF-1 in these cells after virus infection was clearly
      observed. Higher BM retention and homing of CXCR4-expressing MSCs were also found
      after they were transplanted by intramedullary and tail vein injections,
      respectively, into immunocompetent C3H/HeN mice. Interestingly, a full recovery
      of bone mass and a partial restoration of bone formation in glucocorticoid
      induced osteoporotic mice were observed 4 wk after a single intravenous infusion
      of one million CXCR4-expressing C3H10T1/2 cells. In the meantime, complete
      recovery of bone stiffness and strength in these animals was consistently
      detected only after a systemic transplantation of CXCR4 and Cbfa-1 co-transduced
      MSCs. To our knowledge, this is the first report to show unequivocally the
      feasibility of ameliorating glucocorticoid-induced osteoporosis by systemic
      transplantation of genetically manipulated MSCs.

PMID- 19113919
TI  - Atp6v0d2 is an essential component of the osteoclast-specific proton pump that
      mediates extracellular acidification in bone resorption.
AB  - Bone resorption relies on the extracellular acidification function of vacuolar (V
      ) ATPase proton pump(s) present in the plasma membrane of osteoclasts. The exact
      configuration of osteoclast-specific V-ATPases remains largely unknown. In this
      study, we found that Atp6v0d2 (d2), an isoform of the d subunit in the V-ATPase,
      showed 5-fold higher expression than that of Atp6v0d1 (d1) in mature osteoclasts,
      indicating a potential function in osteoclastic bone resorption. When d2 was
      depleted at an early stage of RANKL-induced osteoclast differentiation in vitro,
      formation of multinucleated cells was severely impaired. However, depletion of d2
      at a late differentiation stage did not affect osteoclast fusion but did abolish
      the activity of extracellular acidification and bone resorption of mature
      osteoclasts. We also showed the association of the two tagged-proteins d2 and a3
      when co-expressed in mammalian cells with a co-immunoprecipitation assay.
      Moreover, glutathione-S-transferase (GST) pull-down assay showed the direct
      interaction of d2 with the N terminus of Atp6v0a3 (a3), which is the functionally
      identified osteoclast-specific component of V-ATPase. Therefore, our results show
      the dual function of d2 as a regulator of cell fusion in osteoclast
      differentiation and as an essential component of the osteoclast-specific proton
      pump that mediates extracellular acidification in bone resorption.

PMID- 19113921
TI  - Genome-wide haplotype association mapping in mice identifies a genetic variant in
      CER1 associated with BMD and fracture in southern Chinese women.
AB  - BMD is a heritable trait and risk indicator for osteoporosis. In this study, we
      used a genome-wide haplotype association mapping (HAM) approach to identify a
      haplotype block within Cer1 that partitions inbred mice strains into high and low
      BMD groups. A cohort of 1083 high and low BMD human subjects were studied, and a
      nonsynonymous SNP (rs3747532) in human CER1 was identified to be associated with
      increased risk of both low BMD in premenopausal women (OR: 2.2; 95% CI: 1.0-4.6;
      p < 0.05) and increased risk of vertebral fractures (OR: 1.82, p = 0.025) in the
      postmenopausal cohort. We also showed that Cer1 is expressed in mouse bone and
      growth plate by RT-PCR, immunohistochemistry, and in situ hybridization,
      consistent with polymorphisms potentially influencing BMD. Our successful
      identification of an association with CER1 in humans together with our mouse
      study suggests that CER1 may play a role in the development of bone or its
      metabolism. Our study highlights the use of publicly available databases for
      rapidly surveying the genome for quantitative trait loci.

PMID- 19113922
TI  - Vitamin K treatment reduces undercarboxylated osteocalcin but does not alter bone
      turnover, density, or geometry in healthy postmenopausal North American women.
AB  - Low vitamin K status is associated with low BMD and increased fracture risk.
      Additionally, a specific menaquinone, menatetrenone (MK4), may reduce fracture
      risk. However, whether vitamin K plays a role in the skeletal health of North
      American women remains unclear. Moreover, various K vitamers (e.g., phylloquinone
      and MK4) may have differing skeletal effects. The objective of this study was to
      evaluate the impact of phylloquinone or MK4 treatment on markers of skeletal
      turnover and BMD in nonosteoporotic, postmenopausal, North American women. In
      this double-blind, placebo-controlled study, 381 postmenopausal women received
      phylloquinone (1 mg daily), MK4 (45 mg daily), or placebo for 12 mo. All
      participants received daily calcium and vitamin D(3) supplementation. Serum bone
      specific alkaline phosphatase (BSALP) and n-telopeptide of type 1 collagen (NTX)
      were measured at baseline and 1, 3, 6, and 12 mo. Lumbar spine and proximal femur
      BMD and proximal femur geometry were measured by DXA at baseline and 6 and 12 mo.
      At baseline, the three treatment groups did not differ in demographics or study
      endpoints. Compliance with calcium, phylloquinone, and MK4 treatment was 93%,
      93%, and 87%, respectively. Phylloquinone and MK4 treatment reduced serum
      undercarboxylated osteocalcin but did not alter BSALP or NTX. No effect of
      phylloquinone or MK4 on lumbar spine or proximal femur BMD or proximal femur
      geometric parameters was observed. This study does not support a role for vitamin
      K supplementation in osteoporosis prevention among healthy, postmenopausal, North
      American women receiving calcium and vitamin D supplementation.

PMID- 19113923
TI  - Atypical femoral fractures, bisphosphonates, and adult hypophosphatasia.
AB  - Lateral subtrochanteric femoral pseudofractures occurring in adults with
      osteomalacia from hypophosphatasia and X-linked hypophosphatemia support the
      hypothesis that atypical femoral fractures in osteoporosis treated with
      bisphosphonates also result from low bone turnover.

PMID- 19113924
TI  - Genetic regulation of bone traits is influenced by sex and reciprocal cross in
      F(2) progeny from GK and F344 rats.
AB  - A genome-wide linkage analysis to identify quantitative trait loci (QTLs) for
      bone phenotypes was performed in an F(2) intercross of inbred spontaneously type
      2 diabetic GK and normoglycemic F344 rats (108 males and 98 females). The aim of
      the study was to locate genome regions with candidate genes affecting trabecular
      and cortical bone and to investigate the effects of sex and reciprocal cross.
      pQCT was used to determine tibial bone phenotypes in the F(2) rats, comprising
      reciprocal crosses with divergent mitochondrial (mt) DNA. Sex and reciprocal
      cross-separated QTL analyses were performed followed by assessment of specific
      interactions. Four genome-wide significant QTLs linked to either cortical vBMD,
      tibia length, body length, or metaphyseal area were identified in males on
      chromosomes (chr) 1, 8, and 15. In females, three significant QTLs linked to
      cortical BMC or metaphyseal total vBMD were identified on chr 1 and 2. Several
      additional suggestive loci for trabecular and cortical traits were detected in
      both males and females. Four female-specific QTLs on chr 2, 3, 5, and 10 and four
      reciprocal cross-specific QTLs on chr 1, 10, and 18 were identified, suggesting
      that both sex and mt genotype influence the expression of bone phenotypes.

PMID- 19113925
TI  - Increased bone resorption is associated with higher mortality in community
      dwelling men >or=50 years of age: the MINOS study.
AB  - Low BMD, high concentration of 17beta-estradiol (17betaE2), and decreased level
      of 25-hydroxycholecalciferol [25(OH)D] predict mortality. Our hypothesis is that
      high levels of biochemical bone turnover markers (BTMs) are independent
      predictors of mortality in home-dwelling men. In 781 men >or=50 yr of age
      followed up prospectively for 10 yr, we studied the association of BTMs with
      mortality after adjustment for confounders including BMD, major osteoporotic
      fractures, and concentrations of 17betaE2 and 25(OH)D. Men who died had lower BMD
      and higher BTM levels. In multivariate models, mortality was higher in men with
      low BMD (lowest quartile) at the total hip, whole body, and ultradistal radius
      (HR = 1.49-1.70, p < 0.05). After exclusion of the first 3 yr, higher levels
      (fourth quartile) of bone resorption markers (free and total deoxypyridinoline
      and urinary and serum type I collagen C-telopeptide) predicted mortality in
      multivariate models adjusted for age, BMI, smoking habits, alcohol intake,
      physical performance and activity, comorbidities, total hip BMD, major
      osteoporotic fractures, creatinine clearance, season, and concentrations of
      17betaE2 and 25(OH)D (HR = 1.58-2.44, p < 0.05-0.001). In conclusion, in older
      community-dwelling men, increased bone resorption markers levels predicted
      mortality regardless of age and other confounders. Thus, in older men, high bone
      resorption may reflect poor current health status and poor aging.

PMID- 19113926
TI  - Retreatment with teriparatide one year after the first teriparatide course in
      patients on continued long-term alendronate.
AB  - Patients treated with teriparatide after prior and ongoing alendronate therapy
      experience spine BMD increases; however, some continue to be at high risk for
      fracture, based on persistently low BMD and/or fracture history. The objective of
      this study was to determine whether a second discrete retreatment course with
      teriparatide could produce similar biochemical and BMD changes as seen during the
      first teriparatide course. In the original treatment study, 126 women on
      alendronate for >or=1 yr were randomized to continue alendronate and receive
      daily teriparatide, cyclic teriparatide (3-mo cycles), or alendronate alone for
      15 mo. Of the 72 patients who completed either original teriparatide regimen, 49
      completed a 12-mo follow-up on continued alendronate alone. At that time, 32
      patients, who remained at high risk of future fracture, were recruited into the
      retreatment protocol and 27 completed another course of teriparatide administered
      daily for 15 mo (including 15 from the original daily treatment group and 12 from
      the original cyclic treatment group). Bone formation indices (propeptide of type
      I procollagen and osteocalcin) increased during both teriparatide courses with
      median 3-mo increments of 120% and 72% above baseline during the original course
      and 60% and 40% above baseline during retreatment, respectively. Mean spine BMD
      increments were 6.2% after the first daily course and 4.7% after retreatment and
      4.1% after the first course of cyclic teriparatide and 4.9% after retreatment. We
      conclude that retreatment with teriparatide stimulates bone formation and
      increases spine BMD to a similar extent as seen during the original teriparatide
      course. Retreatment with teriparatide may be a viable option for some patients
      with severe osteoporosis who have received prior teriparatide therapy.

PMID- 19113927
TI  - Positive regulation of adult bone formation by osteoblast-specific transcription
      factor osterix.
AB  - Osterix (Osx) is essential for osteoblast differentiation and bone formation,
      because mice lacking Osx die within 1 h of birth with a complete absence of
      intramembranous and endochondral bone formation. Perinatal lethality caused by
      the disruption of the Osx gene prevents studies of the role of Osx in bones that
      are growing or already formed. Here, the function of Osx was examined in adult
      bones using the time- and site-specific Cre/loxP system. Osx was inactivated in
      all osteoblasts by Col1a1-Cre with the activity of Cre recombinase under the
      control of the 2.3-kb collagen promoter. Even though no bone defects were
      observed in newborn mice, Osx inactivation with 2.3-kb Col1a1-Cre exhibited
      osteopenia phenotypes in growing mice. BMD and bone-forming rate were decreased
      in lumbar vertebra, and the cortical bone of the long bones was thinner and more
      porous with reduced bone length. The trabecular bones were increased, but they
      were immature or premature. The expression of early marker genes for osteoblast
      differentiation such as Runx2, osteopontin, and alkaline phosphatase was markedly
      increased, but the late marker gene, osteocalcin, was decreased. However, no
      functional defects were found in osteoclasts. In summary, Osx inactivation in
      growing bones delayed osteoblast maturation, causing an accumulation of immature
      osteoblasts and reducing osteoblast function for bone formation, without apparent
      defects in bone resorption. These findings suggest a significant role of Osx in
      positively regulating osteoblast differentiation and bone formation in adult
      bone.

PMID- 19113929
TI  - Severity of vertebral fractures is associated with alterations of cortical
      architecture in postmenopausal women.
AB  - Patients with vertebral fractures (VFx) have trabecular architectural disruption
      on iliac biopsies. Because cortical bone is an important determinant of bone
      strength, we assessed cortical and trabecular microarchitecture at peripheral
      sites in patients with VFx of varying number (N) and severity (S). Bone
      architecture and volumetric density (vBMD) were assessed at the distal radius and
      tibia with HR-pQCT (XTreme CT; Scanco Medical, Bassersdorf, Switzerland) in 100
      women with VFx (age, 74 +/- 9 yr) of different S (GI, n = 23; GII, n = 35 ; GIII,
      n = 42) and in 362 women (age, 69 +/- 7 yr) without peripheral or VFx (G0) from
      the OFELY study. Spine areal BMD (aBMD) was assessed by DXA. Among all women, at
      the radius and after adjustment for age and aBMD, there were significant trends
      in lower vBMD, cortical thickness (Cort.Th), trabecular number (Tb.N) and
      thickness (Tb.Th), higher trabecular separation (Tb.Sp), and distribution of
      separation (Tb.Sp.SD) with greater VFx S and N. Among women with VFx, lower
      Cort.Th and cortical vBMD (D.Cort) were associated with severe (GIII) and
      multiple (n > 2) VFx (p < 0.05). The age-adjusted OR for each SD decrease of
      Cort.Th was 2.04 (95% CI, 1.02-4.00) after adjustment for aBMD. At the tibia,
      there were trends for lower vBMD, Tb.N, Tb.Th, and higher Tb.Sp and Tb.Sp.SD with
      greater VFx S and N (p < 0.001). Among women with VFx, lower Cort.Th and D.Cort
      were associated with severe and multiple (n > 3) VFx (p < 0.01). In
      postmenopausal women, VFx are associated with low vBMD and architectural decay of
      trabecular and cortical bone at the radius and tibia, independently of spine
      aBMD. Severe and multiple VFx are associated with even more alterations of
      cortical bone.

PMID- 19113928
TI  - Localization of the cis-enhancer element for mouse type X collagen expression in
      hypertrophic chondrocytes in vivo.
AB  - The type X collagen gene (Col10a1) is a specific molecular marker of hypertrophic
      chondrocytes during endochondral bone formation. Mutations in human COL10A1 and
      altered chondrocyte hypertrophy have been associated with multiple skeletal
      disorders. However, until recently, the cis-enhancer element that specifies
      Col10a1 expression in hypertrophic chondrocytes in vivo has remained
      unidentified. Previously, we and others have shown that the Col10a1 distal
      promoter (-4.4 to -3.8 kb) may harbor a critical enhancer that mediates its
      tissue specificity in transgenic mice studies. Here, we report further
      localization of the cis-enhancer element within this Col10a1 distal promoter by
      using a similar transgenic mouse approach. We identify a 150-bp Col10a1 promoter
      element (-4296 to -4147 bp) that is sufficient to direct its tissue-specific
      expression in vivo. In silico analysis identified several putative transcription
      factor binding sites including two potential activator protein-1 (AP-1) sites
      within its 5'- and 3'-ends (-4276 to -4243 and -4166 to -4152 bp), respectively.
      Interestingly, transgenic mice using a reporter construct deleted for these two
      AP-1 elements still showed tissue-specific reporter activity. EMSAs using
      oligonucleotide probes derived from this region and MCT cell nuclear extracts
      identified DNA/protein complexes that were enriched from cells stimulated to
      hypertrophy. Moreover, these elements mediated increased reporter activity on
      transfection into MCT cells. These data define a 90-bp cis-enhancer required for
      tissue-specific Col10a1 expression in vivo and putative DNA/protein complexes
      that contribute to the regulation of chondrocyte hypertrophy. This work will
      enable us to identify candidate transcription factors essential both for skeletal
      development and for the pathogenesis of skeletal disorders.

PMID- 19113931
TI  - Subtrochanteric and diaphyseal femur fractures in patients treated with
      alendronate: a register-based national cohort study.
AB  - Alendronate (aln) is a potent bisphosphonate with a prolonged duration of action.
      Recent reports have found long-term aln use to be common in patients with
      subtrochanteric or proximal diaphyseal femur fracture, raising concerns that
      these fractures could be a consequence of excessive suppression of bone turnover.
      Two national observational register-based studies were performed: (1) cross
      sectional study (N = 11,944) comparing age distribution, exposure, and trauma
      mechanisms between different types of proximal femur fractures and (2) matched
      cohort study in patients with prior nonhip fractures (N = 5187 + 10,374), testing
      the hypothesis that the increase in the risk of subsequent atypical femur
      fractures exceeded the increase in typical hip fractures. We also sought evidence
      of a dose-response relationship, where high adherence to or long-term use of aln
      led to more atypical femur fractures. We found that 7% of patients with atypical
      fractures were aln exposed, and the same was found for typical hip fractures. In
      the cohort study, the HR for subtrochanteric/diaphyseal fracture with aln was
      1.46 (0.91-2.35, p = 0.12) compared with 1.45 (1.21-1.74, p < 0.001) for hip
      fracture after adjustment for comorbidity and co-medications. The risk was
      reduced by high adherence, and the ratio between hip and
      subtrochanteric/diaphyseal femur fractures was identical in aln-treated patients
      and the control cohort even in the limited number of patients who received long
      term treatment. Subtrochanteric/diaphyseal femur fractures share the epidemiology
      and treatment response of classical hip fractures and are best classified as
      osteoporotic fractures.

PMID- 19113930
TI  - Risk factors for severity and type of the hip fracture.
AB  - More severe hip fractures such as displaced femoral neck (FN) fractures and
      unstable intertrochanteric (IT) fractures lead to poorer outcomes, but risk
      factors for severe fractures have not been studied. To identify risk factors for
      severe types of hip fracture, we performed a prospective cohort study and
      obtained preoperative hip radiographs from women who sustained an incident hip
      fracture (excluding traumatic fractures). A single radiologist scored the
      severity of FN fractures by the Garden System: grades I and II, undisplaced;
      grades III and IV, displaced. The severity of IT hip fractures was rated by the
      Kyle System: grades I and II, stable; grades III and IV, unstable. A total of 249
      women had FN fractures: 75 (30%) were undisplaced. A total of 213 women had IT
      fractures: 59 (28%) were stable. Both types of hip fracture increased with age,
      but older age was even more strongly associated with more severe hip fractures.
      Low BMD was more strongly related to undisplaced FN fractures (p interaction BMD
      x FN type, p = 0.0008) and stable IT fractures (p interaction BMD x IT type, p =
      0.04). Similar findings were observed for estimated volumetric BMD and hip
      geometric parameters. Corticosteroid use was only associated with displaced FN
      fractures, and Parkinson's disease was only associated with stable IT fractures.
      Little difference was reported in the self-reported circumstances surrounding
      each type of fracture. In conclusion, the lower the BMD, the greater the
      likelihood of experiencing a hip fracture that is less displaced and more stable.

PMID- 19113932
TI  - A simple risk score for the assessment of absolute fracture risk in general
      practice based on two longitudinal studies.
AB  - The aim of this prospective study was to develop a risk score, based on putative
      risk factors in current guidelines, which can be used to identify women at high
      risk of fractures in general practice. The study sample included 4157 women >/=60
      yr of age (mean +/- SD: 74.1 +/- 9.1 yr), with a median follow-up of 8.9 yr of
      the Rotterdam Study (ERGO), and 762 women >/=65 yr of age (mean +/- SD: 76.0 +/-
      6.7.yr), with a median follow-up of 6.0 yr of the Longitudinal Aging Study
      Amsterdam (LASA). Potential risk factors were those proposed in risk scores of
      three recent guidelines on osteoporosis: age, family history of fractures, prior
      fracture, low body weight/body mass index (BMI), serious immobility, rheumatoid
      arthritis, current smoking, alcohol consumption >2 units daily, prevalent
      vertebral fracture, and systemic corticosteroid use. Five-year absolute risk of
      hip fracture was 3.9% in the Rotterdam Study and 3.1% in LASA, and 10-yr absolute
      risk of hip fracture was 8.4% in the Rotterdam Study. Using Cox regression
      analysis, age (70-79 and 80+ versus <60-69) and four other risk factors were
      included in the risk profiles of hip fractures and fragility fractures: any prior
      fracture after age 50, body weight <64 kg, use of a walking aid as a proxy
      measure of serious immobility, and current smoking. Estimated 10-yr absolute risk
      of hip fracture ranged from 1.4% in women, age 60-69 years, without any of these
      predictors to 29% in women, >/=80 yr of age, having two or more positive risk
      factors. A simple risk score can satisfactorily identify older women at high risk
      of osteoporotic fractures in general practice. Future studies are needed to
      validate this score.

PMID- 19113933
TI  - Genome-wide analysis of genes related to kidney stone formation and elimination
      in the calcium oxalate nephrolithiasis model mouse: detection of stone-preventive
      factors and involvement of macrophage activity.
AB  - We previously established a mouse kidney stone formation model and showed that
      mice have a higher tolerance to stone formation than rats. Furthermore, we showed
      that the generated calcium oxalate crystal deposits could be eliminated after
      several days. This study investigated the transcriptome of stone formation and
      elimination in the mouse kidney based on gene selection using a microarray
      technique. Eight-week-old male C57BL/6N mice were administered 80 mg/kg
      glyoxylate for 15 days, and kidney calcium oxalate crystal depositions had
      increased by day 6; thereafter, depositions decreased gradually and had almost
      disappeared by day 15. On microarray analysis, mRNA expression in the crystal
      formed kidneys showed the significant expression of 18,064 genes. Thirty-one, 21,
      and 25 genes showed at least a 2-fold increased expression during the
      experimental course (days 3-15), stone formation phase-specific (days 3-6), and
      stone elimination phase-specific (days 9-15) stages, respectively. Among these
      genes, those related to chemotaxis and monocyte/macrophage activation were
      identified. Gene ontology analysis to identify overexpressed genes highlighted
      categories related to inflammation, immune reactions and the complement
      activation pathway. Quantitative PCR of 17 previously reported stone-related
      genes with a significant expression on microarray analysis showed significantly
      increased chemokines, stone matrix proteins, and their receptors; the significant
      decrease of several types of transporters and superoxide dismutase; and the
      persistently high expression of Tamm-Horsfall protein throughout the experiment.
      In conclusion, inflammation and immune reactivity through macrophage migration
      are involved in stone formation and elimination in mouse kidneys.

PMID- 19113934
TI  - Formation of carbonato and hydroxo complexes in the reaction of platinum
      anticancer drugs with carbonate.
AB  - The second-generation Pt(II) anticancer drug carboplatin is here shown to react
      with carbonate, which is present in blood, interstitial fluid, cytosol, and
      culture medium, to produce platinum-carbonato and -hydroxo complexes. Using [(1)H
      (15)N] HSQC NMR and (15)N-labeled carboplatin, we observe that cis-[Pt(CBDCA
      O)(OH)(NH(3))(2)](-), cis-[Pt(OH)(2)(NH(3))(2)], cis-[Pt(CO(3))(OH)(NH(3))(2)](
      ), and what may be cis-[Pt(CO(3))(NH(3))(2)] are produced when 1 is allowed to
      react in 23.8 mM carbonate buffer. When (15)N-labeled carboplatin is allowed to
      react in 0.5 M carbonate buffer, these platinum species, as well as other hydroxo
      and carbonato species, some of which may be dinuclear complexes, are produced.
      Furthermore, we show that the carbonato species cis-[Pt(CO(3))(OH)(NH(3))(2)](-)
      is also produced when cisplatin is allowed to react in carbonate buffer. The
      study outlines the conditions under which carboplatin and cisplatin form
      carbonato and aqua/hydroxo species in carbonate media.

PMID- 19113935
TI  - Squaramide hydroxamate-based chemidosimeter responding to iron(III) with a
      fluorescence intensity increase.
AB  - The synthesis and in vitro evaluation of a squarate hydroxamate-coumarin
      conjugate, 12, as a chemodosimeter for Fe(III) and other oxidants, such as Cr(VI)
      and Ce(IV), is described. As 12 was originally designed to become a chelation
      enhanced fluorescence (CHEF)-type sensor for Fe(III), the competence of the
      squarate diamide platform to relay a CHEF response was demonstrated using a zinc
      binding, cyclen-substituted squarate coumarin amide. Due to a photo electron
      transfer process, 12 possesses a low fluorescence yield. Upon exposure of 12 to
      Fe(III) (or other oxidants), an irreversible 9-fold fluorescence intensity
      increase is observed as the result of an oxidation/hydrolysis reaction. The
      (aminomethyl)coumarin portion of 12 is oxidized to an iminocoumarin that
      hydrolyzes to produce a highly fluorescent coumarinaldehyde. Fe(III) acts as a
      catalyst in this transformation, thereby enhancing the sensitivity of the system
      for the detection of Fe(III) down to 1 ppm in aqueous buffer solution. The
      identities of the major reaction products between 12 and Fe(III) were proven by
      independent synthesis.

PMID- 19113936
TI  - Alkylation of 2-substituted (6-methyl-2-pyridyl)methyllithium species with
      epoxides.
AB  - Substituted (6-methyl-2-pyridyl)methyllithium species were reacted with 1,2
      epoxyoctane and 2-methyl-2,3-epoxynonane. The monosubstituted epoxide reacted
      efficiently with lutidyllithium and a number of 2-substituted (6-methyl-2
      pyridyl)methyllithium derivatives. The trisubstituted epoxide gave low yields of
      adducts with all (2-pyridyl)methyllithium species studied. These results are
      discussed in the context of a proposed synthesis of cananodine.

PMID- 19113937
TI  - Synthesis of oxindoles by tandem Heck-reduction-cyclization (HRC) from a single
      bifunctional, in situ generated Pd/C catalyst.
AB  - A tandem sequence involving palladium-catalyzed sequential Heck-reduction
      cyclization transformations in mild conditions has been developed for the
      synthesis of oxindoles. The protocol involves inexpensive reagents and does not
      require any additives such as base or ligands.

PMID- 19113938
TI  - Comparison of the reactivity of bis(mu-oxo)Cu(II)Cu(III) and Cu(III)Cu(III)
      species to methane.
AB  - Methane hydroxylation at the dinuclear copper site of particulate methane
      monooxygenase (pMMO) is studied by using density functional theory (DFT)
      calculations. The electronic and structural properties of the dinuclear copper
      species of bis(mu-oxo)Cu(II)Cu(III) and Cu(III)Cu(III) are discussed with respect
      to the C-H bond activation of methane. The bis(mu-oxo)Cu(II)Cu(III) species is
      highly reactive and considered to be an active species for the conversion of
      methane to methanol by pMMO, whereas the bis(mu-oxo)Cu(III)Cu(III) species is
      unable to react with methane as it is. If a Cu-O bond of the bis(mu
      oxo)Cu(III)Cu(III) species is cleaved, the resultant Cu(III)Cu(III) species, in
      which only one oxo ligand bridges the two copper ions, can activate methane.
      However, its energetics for methane hydroxylation is less favorable than that by
      the bis(mu-oxo)Cu(II)Cu(III) species. The DFT calculations show that the bis(mu
      oxo)Cu(II)Cu(III) species is more effective for the activation of methane than
      the bis(mu-oxo)Cu(III)Cu(III) species. The reactive bis(mu-oxo)Cu(II)Cu(III)
      species can be created either from the electron injection to the bis(mu
      oxo)Cu(III)Cu(III) species or from the O-O bond cleavage in the mu-eta(1):eta(2)
      peroxoCu(I)Cu(II) species.

PMID- 19113939
TI  - Total and percent atropisomers of gossypol and gossypol-6-methyl ether in seeds
      from pima cottons and accessions of Gossypium barbadense L.
AB  - Gossypol occurs naturally in the seed, foliage, and roots of the cotton plant (
      Gossypium ) as atropisomers due to restricted rotation around the binaphthyl
      bond. The atropisomers differ in their biological activities. (-)-(R)-Gossypol is
      more toxic and exhibits significantly greater anticancer activity than the (+)
      (S)-atropisomer. Most commercial Upland ( Gossypium hirsutum ) cottonseeds have
      an (R)- to (S)-gossypol ratio of approximately 2:3, but some Pima ( Gossypium
      barbadense ) seeds have an excess of (R)-gossypol. There is no known source of
      cottonseed with an (R)- to (S)-gossypol ratio of greater than approximately
      70:30. Cottonseed with a high percentage of (R)-gossypol would be of value to the
      pharmaceutical industry. It was theorized that G. barbadense cotton might be a
      source of this desirable high (R)-gossypol seed trait. There are 671 different
      accessions of G. barbadense in the U.S. Cotton Germplasm Collection, few of which
      had been characterized with respect to their (R)- to (S)-gossypol ratio. This
      work completed that analysis and found considerable variation in the atropisomer
      ratio. Approximately half of the accessions have an excess of (R)-gossypol, and
      52 accessions have essentially a 1:1 ratio. The highest percentage of (R)
      gossypol was found in accessions GB26 (68.2%) and GB283 (67.3%). Surprisingly,
      five accessions had 5% or less of (R)-gossypol: GB516 (5.0%), GB761 (4.5%), GB577
      (4.3%), GB719 (3.7%), and GB476 (2.3%). These accessions may be useful in a
      breeding program to reduce (R)-gossypol in Pima seed, which is a concern to the
      dairy industry because of the toxicity and male antifertility activity of this
      atropisomer. Also, GB710 was devoid of gossypol.

PMID- 19113940
TI  - Design of silica networks for development of highly permeable hydrogen separation
      membranes with hydrothermal stability.
AB  - A sol-gel method was applied for the development of highly permeable hydrogen
      separation membranes using bis(triethoxysilyl)ethane (BTESE) as a silica
      precursor. Hybrid silica membranes showed quite high hydrogen permeance (1 x 10(
      5) mol m(-2) s(-1) Pa(-1)) with a high H(2)-to-SF(6) selectivity of 1000 because
      of loose organic-inorganic silica networks. Hybrid silica membranes were found to
      show high hydrothermal stability due to the presence of Si-C-C-Si bonds in silica
      networks.

PMID- 19113941
TI  - Identification and verification of lysine propionylation and butyrylation in
      yeast core histones using PTMap software.
AB  - Ten types of post-translational modifications (PTMs) known to be critical to
      diverse cellular functions have been described in core histone proteins. However,
      it remains unclear whether additional PTMs exist in histones, and if so, what
      roles these undiscovered signals play in epigenetic phenomena. Here, we report a
      systematic analysis of yeast histone PTMs by mass spectrometry in combination
      with protein sequence alignment using PTMap, a computer program we recently
      developed. We have identified, for the first time, multiple sites of lysine
      propionylation and butyrylation in yeast histones H2B, H3, and H4. We confirmed
      these modifications by Western blotting using modification-specific antibodies,
      MS/MS of synthetic peptides, and coelution of synthetic and in vivo-derived
      peptides from an HPLC column. The presence of multiple modification sites in
      several yeast histones suggests that these two PTMs are histone marks that are
      evolutionarily conserved among eukaryotes. In addition, we identified 14 novel
      mass shifts that do not match any known PTM, suggesting the presence of
      previously undescribed histone modifications. The chemical natures of these
      modifications remain to be determined. Our studies therefore expand current
      knowledge of the "histone code".

PMID- 19113942
TI  - Mass spectrometry studies of the binding of the minor groove-directed alkylating
      agent alkamin to AT-tract oligonucleotides.
AB  - Minor groove binding alkylating agents, which have potential as cancer drugs,
      generate cytotoxic DNA adducts that are relatively resistant to repair as a
      consequence of locating covalent attachment at purine N3 nitrogen atoms.
      Recently, we used electrospray and matrix-assisted laser desorption ionization
      mass spectrometry to study the binding of the minor groove-directed polybenzamide
      bis-half-mustard alkamin, and its monofunctional analogue alkamini, to the
      oligonucleotide d(CGCGAATTCGCG)(2), identifying a number of inter- and
      intrastrand alkamin cross-links involving the GAATTC sequence [ Abdul Majid , A.
      M. S. , Smythe , G. , Denny , W. A. , and Wakelin , L. P. G. ( 2007 ) Mol.
      Pharmacol. 71 , 1165 - 1178 ]. Here, we extend these studies to
      d(CGCAAATTTGCG)(2), A3T3, and d(CGCAAAAAAGCG).d(CGCTTTTTTGCG), A6/T6, in which
      the opportunity for both inter- and intrastrand cross-linking is enhanced. We
      find that both ligands alkylate all adenines in the longer AT-tracts, as well as
      the abutting guanines, whether they are in the same strand as the adenines or
      not, in a manner consistent with covalent attack on purine N3 atoms from the
      minor groove. Alkamin forms intrastrand cross-links involving A4 and A6 and A6
      and G10 in A3T3 and all of the purines in the A6/T6 purine tract, including G10.
      In addition, it forms interstrand cross-links between A4, A5, A6 and A4', A5',
      A6', between G10 and the latter adenines in A3T3, and between G22 and adenines A5
      and A6 in A6/T6. The reactivity of the abutting guanines provides unexpected
      opportunities for both inter- and intrastrand cross-linking by alkamin, such as
      the interstrand cross-link in the CAAAAAAG sequence. We conclude that positioning
      monofunctional mustard groups on either end of a minor groove-directed
      polybenzamide has the capacity to enhance interstrand cross-links at all manner
      of AT-tracts, including most in which the adenines are all in one strand.

PMID- 19113943
TI  - Extracting both peptide sequence and glycan structural information by 157 nm
      photodissociation of N-linked glycopeptides.
AB  - The 157 nm photodissociation of N-linked glycopeptides was investigated in MALDI
      tandem time-of-flight (TOF) and linear ion trap mass spectrometers. Singly
      charged glycopeptides yielded abundant peptide and glycan fragments. The peptide
      fragments included a series of x-, y-, v-, and w- ions with the glycan remaining
      intact. These provide information about the peptide sequence and the
      glycosylation site. In addition to glycosidic fragments, abundant cross-ring
      glycan fragments that are not observed in low-energy CID were detected. These
      fragments provide insight into the glycan sequence and linkages. Doubly charged
      glycopeptides generated by nanospray in the linear ion trap mass spectrometer
      also yielded peptide and glycan fragments. However, the former were dominated by
      low-energy fragments such as b- and y- type ions while glycan was primarily
      cleaved at glycosidic bonds.

PMID- 19113944
TI  - A sensitive and robust competitive enzyme-linked immunosorbent assay for Brazil
      nut ( Bertholletia excelsa L.) detection.
AB  - Undeclared Brazil nut residue in food products is of great concern because it can
      trigger life-threatening allergic reactions in sensitive patients. A rabbit
      polyclonal antibody-based competitive ELISA (IC(50) = 23.2 +/- 9 ng/mL, n = 76)
      with good sensitivity, detection range of 10-90 ng/mL, was developed. The ELISA
      could detect Brazil nut seed proteins over a pH range of 5-12. The optimal pH
      range for the detection assay was 7-10. Among the 66 tested foods/ingredients,
      only cinnamon exhibited statistically significant interference (1.36%, p = 0.05).
      Exposing Brazil nut seeds to processing did not adversely affect the nut seed
      protein detection using the assay. Brazil nut seed protein recovery from 100 mg
      of foods spiked with 10 and 1 microg of soluble Brazil nut proteins or 100 and 10
      microg of defatted Brazil nut flour exhibited a wide recovery range, 63-315%,
      indicating protein-food matrix interaction.

PMID- 19113945
TI  - Metal tetraphosphonate "wires" and their corrosion inhibiting passive films.
AB  - Herein, we describe the preparation and characterization of five new divalent
      metal tetraphosphonates, M-HDTMP [M = Mg(2+), Ca(2+), Sr(2+), Ba(2+), and Cu(2+);
      HDTMP = hexamethylenediaminetetrakis(methylenephosphonate) dianion]. Materials
      {Sr[(HDTMP)(H(2)O)(6)] x 2 H(2)O}(n) (1), {Ba[(HDTMP)(H(2)O)(6)] x 2 H(2)O}(n)
      (2), and {Cu[(HDTMP)(H(2)O)(4)] x 6 H(2)O}(n) (3), as well as (en)(HDTMP) x 2
      H(2)O (en = ethylenediammonium cation) have been structurally characterized.
      Structures depend on the coordination requirements of the M(2+) center and waters
      of crystallization content. The formation and characterization of effective
      anticorrosion passive films of M-HDTMP (M = Sr(2+) and Ba(2+)) are also reported.

PMID- 19113946
TI  - Accurate simulation of optical properties in dyes.
AB  - Since Antiquity, humans have produced and commercialized dyes. To this day,
      extraction of natural dyes often requires lengthy and costly procedures. In the
      19th century, global markets and new industrial products drove a significant
      effort to synthesize artificial dyes, characterized by low production costs, huge
      quantities, and new optical properties (colors). Dyes that encompass classes of
      molecules absorbing in the UV-visible part of the electromagnetic spectrum now
      have a wider range of applications, including coloring (textiles, food,
      paintings), energy production (photovoltaic cells, OLEDs), or pharmaceuticals
      (diagnostics, drugs). Parallel to the growth in dye applications, researchers
      have increased their efforts to design and synthesize new dyes to customize
      absorption and emission properties. In particular, dyes containing one or more
      metallic centers allow for the construction of fairly sophisticated systems
      capable of selectively reacting to light of a given wavelength and behaving as
      molecular devices (photochemical molecular devices, PMDs).Theoretical tools able
      to predict and interpret the excited-state properties of organic and inorganic
      dyes allow for an efficient screening of photochemical centers. In this Account,
      we report recent developments defining a quantitative ab initio protocol (based
      on time-dependent density functional theory) for modeling dye spectral
      properties. In particular, we discuss the importance of several parameters, such
      as the methods used for electronic structure calculations, solvent effects, and
      statistical treatments. In addition, we illustrate the performance of such
      simulation tools through case studies. We also comment on current weak points of
      these methods and ways to improve them.

PMID- 19113947
TI  - Tandem beta-enamino ester formation and cyclization with o-alkynyl anilines
      catalyzed by InBr3: efficient synthesis of beta-(N-indolyl)-alpha,beta
      unsaturated esters.
AB  - A tandem reaction providing beta-(N-indolyl)-alpha,beta-unsaturated esters from
      beta-keto esters and o-alkynyl anilines was developed. Z-Alkenes were selectively
      formed due to the stability of the beta-enamino ester as an intermediate of the
      reaction. This reaction includes the intermolecular beta-enamino ester formation
      and intramolecular cyclization catalyzed by InBr(3).

PMID- 19113948
TI  - Antibacterial and antifouling polymer brushes incorporating antimicrobial
      peptide.
AB  - Surface-initiated atom transfer radical polymerization (ATRP) has been used to
      prepare antifouling copolymer brushes based on 2-(2-methoxyethoxy)ethyl
      methacrylate (MEO(2)MA) and hydroxyl-terminated oligo(ethylene glycol)
      methacrylate (HOEGMA). The amount of hydroxyl reactive groups incorporated into
      the brushes was varied by changing the composition of the monomer mixture. These
      coatings were subsequently functionalized by a natural antibacterial peptide,
      magainin I, via an oriented chemical grafting on hydroxyl groups, which maintains
      the activity of the peptide. The antibacterial activity of the functionalized
      brushes was successfully tested against two different strains of gram-positive
      bacteria.

PMID- 19113949
TI  - Benefits, risk, and uncertainty: preferences of antiretroviral-naive African
      Americans for HIV treatments.
AB  - While African Americans in the United States are disproportionately affected by
      HIV, they are less likely to take antiretroviral therapies. Different first-line
      antiretroviral therapies are associated with short-term and long-term adverse
      event (AE) risks. We estimated the willingness of antiretroviral-naive, HIV
      positive African Americans to accept risks of acute AEs with known outcomes and
      long-term AEs with uncertain outcomes in exchange for virologic suppression. We
      estimated the relative importance of short-term and long-term AE risks. Two
      hundred thirty-five subjects were recruited through eight clinics in the United
      States. One hundred fifty-eight subjects met study inclusion criteria. One
      hundred fifty-three subjects completed a series of choice-format conjoint trade
      off tasks. In each task, subjects were asked to choose between two hypothetical
      treatments with varying levels of virologic failure, risks of hypersensitivity
      reaction, decreases in bone mineral density (BMD), and renal impairment, and
      outcome uncertainty associated with the risks of decreased BMD and renal
      impairment. Attributes were expressed as probabilities of occurrence. We
      calculated the relative importance of each AE and the level of risk subjects
      would accept to reduce the risk of virologic failure. Subjects indicated that
      short-term AEs with relatively certain outcomes are preferred to long-term AEs
      with uncertain outcomes. Subjects were strongly averse to the risk of decreased
      BMD that could not be treated successfully or when the outcome was uncertain and
      to the risk of renal impairment that could not be treated successfully. Subjects
      were willing to accept increased risks of AEs in exchange for lower risk of
      virologic failure.

PMID- 19113951
TI  - I want products my own way, but which way? The effects of different product
      categories and cues on customer responses to Web-based customizations.
AB  - Mass customization is a strategy that has been adopted by companies to tailor
      their products in order to match customer needs more precisely. Therefore, to
      fully capture the value of mass customization, it is crucial to explore how
      customers react to mass customization. In previous studies, an implied premise
      has been that consumers are keen to embrace customized products, and this
      assumption has also been treated by firms as a prerequisite for successful mass
      customization strategies. However, an undesirable complexity may result from
      difficult configuration processes that may intimidate and confuse some customers.
      Hence, this study explores strategies that marketers can employ to facilitate the
      customization process. Specifically, this study investigates how to enhance
      customer satisfaction and purchase decision toward customized products by
      providing cues compatible with the product category. It is hypothesized that for
      search products, customers rely more on intrinsic cues when making configuration
      decisions. On the other hand, for experience products, customers perceive
      extrinsic cues to be more valuable in assisting them to make configuration
      decisions. The results suggest that consumers tend to respond more favorably
      toward customized search products when intrinsic cues are provided than when
      extrinsic or irrelevant ones are provided. In contrast, when customizing
      experience products, customers tend to depend more on extrinsic cues than on
      intrinsic or irrelevant ones.

PMID- 19113950
TI  - Engineering retina from human retinal progenitors (cell lines).
AB  - Retinal degeneration resulting in the loss of photoreceptors is the leading cause
      of blindness. Several therapeutic protocols are under consideration for treatment
      of this disease. Tissue replacement is one such strategy currently being
      explored. However, availability of tissues for transplant poses a major obstacle.
      Another strategy with great potential is the use of adult stem cells, which could
      be expanded in culture and then utilized to engineer retinal tissue. In this
      study, we have explored a spontaneously immortalized human retinal progenitor
      cell line for its potential in retinal engineering using rotary cultures to
      generate three-dimensional (3D) structures. Retinal progenitors cultured alone or
      cocultured with retinal pigment epithelial cells form aggregates. The aggregate
      size increases between days 1 and 10. The cells grown as a 3D culture rotary
      system, which promotes cell-cell interaction, retain a spectrum of
      differentiation capability. Photoreceptor differentiation in these cultures is
      confirmed by significant upregulation of rhodopsin and AaNat, an enzyme
      implicated in melatonin synthesis (immunohistochemistry and Western blot
      analysis). Photoreceptor induction and differentiation is further attested to by
      the upregulation of rod transcription factor Nrl, Nr(2)e(3), expression of
      interstitial retinal binding protein, and rhodopsin kinase by reverse
      transcription-polymerase chain reaction. Differentiation toward other cell
      lineages is confirmed by the expression of tyrosine hydroxylase in amacrine
      cells, thy 1.1 expression in ganglion cells and calbindin, and GNB3 expression in
      cone cells. The capability of retinal progenitors to give rise to several retinal
      cell types when grown as aggregated cells in rotary culture offers hope that
      progenitor stem cells under appropriate culture conditions will be valuable to
      engineer retinal constructs, which could be further tested for their transplant
      potential. The fidelity with which this multipotential cell line retains its
      capacity to differentiate into multiple cell types holds great promise for the
      use of tissue-specific adult stem cells for therapy.

PMID- 19113952
TI  - Tracing pharmaceutical residues of different therapeutic classes in environmental
      waters by using liquid chromatography/quadrupole-linear ion trap mass
      spectrometry and automated library searching.
AB  - This article describes the development, optimization, and validation of an
      analytical method for the simultaneous detection and identification of 73
      pharmaceutical residues, covering various therapeutic groups, in both surface and
      wastewaters. The method is based on the simultaneous extraction of all target
      compounds by Solid Phase Extraction (SPE), using a hydrophilic-lipophilic
      balanced polymer followed by liquid chromatography tandem mass spectrometry,
      using a hybrid triple quadrupole-linear ion trap mass spectrometer (QqLIT).
      Quantitative analysis was performed using the 4000 Qtrap tandem mass spectrometer
      in Selected Reaction Monitoring (SRM) mode, monitoring two SRM transitions to
      fulfill EC guidelines, as well as to ensure an accurate identification of target
      compounds in the samples. Quantitation is performed by the internal standard
      approach, indispensable to correct matrix effects. Moreover, to obtain an extra
      tool for confirmation and identification of the studied pharmaceuticals, an
      Information Dependent Acquisition (IDA) experiment was performed, with SRM as the
      survey scan and an enhanced product ion (EPI) scan, at three different collision
      energies, as dependent scan. Compound identification was carried out by library
      search with a developed library, created by the infusion of standards, based on
      EPI spectra at the three collision energies. The main advantages of the developed
      method, besides high sensitivity (limits of detection ranging from 0.1-55 ng/L,
      depending on the matrix), selectivity, and reliability of results, are that all
      compounds are extracted in a single step, speeding up considerably sample
      preparation. Recoveries obtained were generally higher than 50% for both surface
      and wastewaters, with the exception of metronidazole (20-30%), salbutamol (33
      43%), atorvastatin (40% in surface water), and nadolol (31% in surface water)
      that yielded lower but still acceptable recoveries. The overall variability of
      the method was below 15%, for all compounds and all matrixes tested. Finally, the
      method developed has been applied to the analysis of various influent and
      effluent wastewaters as well as river waters from Spain.

PMID- 19113953
TI  - Lid opening and unfolding in human pancreatic lipase at low pH revealed by site
      directed spin labeling EPR and FTIR spectroscopy.
AB  - The structural changes induced in human pancreatic lipase (HPL) by lowering the
      pH were investigated using a combined approach involving the use of site-directed
      spin labeling coupled to electron paramagnetic resonance (SDSL-EPR) and Fourier
      transform infrared (ATR-FTIR) spectroscopy. The secondary structure of HPL
      observed with ATR-FTIR spectroscopy was found to be stable in the pH range of 3.0
      6.5, where HPL remained active. Using a spin-label introduced into the lid of HPL
      at position 249, a reversible opening of the lid controlling the access to the
      active site was observed by EPR spectroscopy in the pH range of 3.0-5.0. In the
      same pH range, some structural changes were also found to occur outside the lid
      in a peptide stretch located near catalytic aspartate 176, using a spin-label
      introduced at position 181. Below pH 3.0, ATR-FTIR measurements indicated that
      HPL had lost most of its secondary structure. At these pH levels, the loss of
      enzyme activity was irreversible and the ability of HPL to bind to lipid
      emulsions was abolished. The EPR spectrum of the spin-label introduced at
      position 181, which was typical of a spin-label having a high mobility, confirmed
      the drastic structural change undergone by HPL in this particular region. The EPR
      spectrum of the spin-label at position 249 indicated, however, that the
      environment of this residue within the lid was not affected at pH 3.0 in
      comparison with that observed in the pH range of 3.0-5.0. This finding suggests
      that the disulfide bridge between the hinges of the lid kept the secondary
      structure of the lid intact, whereas the HPL was completely unfolded.

PMID- 19113954
TI  - Edaravone derivatives containing NO-donor functions.
AB  - A new series of polyvalent drugs obtained by joining edaravone with NO-donor
      moieties is described. All compounds display high antioxidant power together with
      NO-dependent vasodilator properties. The analysis of a number of molecular
      descriptors shows that the antioxidant activity, which is tightly linked to the
      presence of the edaravone substructure, is principally modulated by
      lipophilicity. These products are potentially useful in the treatment of
      cardiovascular disorders in which EDRF deficiency and ROS excess are involved.

PMID- 19113955
TI  - Combining 4-aminoquinoline- and clotrimazole-based pharmacophores toward
      innovative and potent hybrid antimalarials.
AB  - Antimalarial agents structurally based on novel pharmacophores, synthesized by
      low-cost synthetic procedures and characterized by low potential for developing
      resistance are urgently needed. Recently, we developed an innovative class of
      antimalarials based on a polyaromatic pharmacophore. Hybridizing the 4
      aminoquinoline or the 9-aminoacridine system of known antimalarials with the
      clotrimazole-like pharmacophore, characterized by a polyarylmethyl group, we
      describe herein the development of a unique class (4a-l and 5a-c) of
      antimalarials selectively interacting with free heme and interfering with
      Plasmodium falciparum (Pf) heme metabolism. Combination of the polyarylmethyl
      system, able to form and stabilize radical intermediates, with the iron
      complexing and conjugation-mediated electron transfer properties of the 4(9)
      aminoquinoline(acridine) system led to potent antimalarials in vitro against
      chloroquine sensitive and resistant Pf strains. Among the compounds synthesized,
      4g was active in vivo against P. chabaudi and P. berghei after oral
      administration and, possessing promising pharmacokinetic properties, it is a
      candidate for further preclinical development.

PMID- 19113956
TI  - Clinical encounters with internet pornography.
AB  - Abstract Pornography, if understood to involve the depiction of sexual activity,
      organs, and experiences, is perhaps as old as human civilization itself.
      Historically linked to various technological innovations, pornography viewing in
      the Internet age has reached epic proportions, with large numbers of individuals
      taking advantage of ease of access, affordability, and presumed anonymity to
      explore sexual material online. Within the mental health professions substantial
      research exists on the effects of viewing general pornography; however, the
      distinctive effects of the marriage of pornography and cyberspace is only
      beginning to be examined. In addition to reviewing some historical and
      statistical material about pornography and the relevant psychiatric and
      psychoanalytic literature, four detailed clinical vignettes are presented to
      illustrate the types of problems related to Internet pornography use that are
      being presented to practicing psychotherapists.

PMID- 19113957
TI  - Attraction to pornographic stories on the internet: a commentary on "clinical
      encounters with internet pornography" by Thomas P. Kalman.

PMID- 19113958
TI  - A psychotherapy model for treating refugee children caught in the midst of
      catastrophic situations.
AB  - A psychotherapy model for treating child and adolescent refugees caught in the
      midst of catastrophic situations is proposed. Empirical studies of the peri
      traumatic period, comprised between the moment of departure and up to the moment
      of arrival of the refugees to the sheltering country, are scarce and difficult to
      complete. A review of the literature reveals that negative, long term mental
      health outcomes in these populations are related to autonomic dysregulation and
      impaired narratives of the events, which result from exposure to overwhelming
      stress. The author combines case material from his own clinical experience
      treating Cuban children and adolescents inside refugee camps, with the available
      literature, in order to design the model. The role of the therapist is threefold
      and involves: (1) intervening to decrease hyperarousal and protect the refugee's
      neuroendocrine integrity, (2) helping the patient construct a cohesive narrative
      of the events during the peri-traumatic period and, (3) becoming an advocate for
      the refugee children and their families, helping to empower them so they can
      attain mastery and control over the forces that threaten to overwhelm their
      coping capacities. This model addresses a neglected area of refugee studies:
      treatment interventions during the peri-traumatic period. It attempts to bridge
      the empirical research gap that exists, due to the inherent difficulties of
      studying refugee populations "in the field." This model could potentially be
      extrapolated to treat other similar populations.

PMID- 19113959
TI  - Humiliation: the trauma of disrespect.
AB  - Humiliation, triggered by sensed insult, is hypothesized as a traumatic stimulus
      and the driving force of a goal-directed survival response that includes
      predictable emotional appraisals, and motivational or behavioral responses.
      Because these responses appear automatic and obligatory, they are most likely
      innately planted as a survival mechanism. Sensitive to developmental experience,
      these psychobiological responses can be intensified or modulated by social
      learning.

PMID- 19113960
TI  - A workshop model for educating medical practitioners about optimal treatment of
      difficult-to-manage patients: utilization of transference-countertransference.
AB  - Some patients are unable to participate in a good, mutually cooperative
      relationship with their primary care doctors. They may have long-standing
      psychosocial difficulties exacerbated by chronic, painful, or life-threatening
      illnesses. Some may have somatic symptoms that they define as evidence only of an
      identified illness but which are reflections of psychic misery with roots in
      their thoughts, feelings, and relationships. This article describes a Workshop
      approach to teaching those patients' physicians how to make diagnostic use of
      their own "gut reactions" to understand the common dynamics of the doctor-
      patient relationship; to understand the psychological aspects of various physical
      symptoms; and manage challenging patients to optimize their quality of life, cost
      effectiveness of treatment and minimize physician "burnout."

PMID- 19113961
TI  - The relevance of Hegel's Phenomenology of Spirit to the process of contemporary
      psychoanalysis.
AB  - Do changes in psychoanalytic technique represent progress in knowledge or are
      they for the most part a sideways movement in tune with the particular changes in
      the socioeconomic milieu of the day? Hegel raised the question in the area of
      philosophy when discussing the stages in the development of self-consciousness.
      For him this was an inevitable development toward a greater and greater self
      understanding, going through various phases until Absolute Spirit (Mind) became
      completely cognizant of itself. This metaphysical conception was the cornerstone
      of Hegel's thought as first presented in his chaotic masterpiece, Phenomenology
      of Spirit. In this article I will examine his philosophical vision as expressed
      in that masterpiece, compare it with that of Freud, and discuss aspects of it
      that are pertinent to the practice of contemporary psychoanalysis.

PMID- 19113962
TI  - Self and time.
AB  - This article explores the meaning of subjective time and its implications for the
      understanding of the nature of the self in psychoanalytic terms. Subjective time,
      the time experience of intrapsychic life, is distinguished from objective time.
      Its development and evolution in the course of the life cycle are examined, and
      various aspects of its phenomenology explored. Implications for the understanding
      of the structure and functioning of the self, especially the combined influence
      of physiological and environmental processes reflecting the integration of body
      mind in the time experience and self-organization are discussed. Some
      implications for the engagement of the self in the analytic process are
      suggested, particularly the focusing of therapeutic interaction in the present
      moment and the implications of the meaning of structural change in reference to
      the modification of the self-concept through the revision and integration of
      memory systems in the present interaction between analyst and analysand.

PMID- 19113963
TI  - A view from Riggs: treatment resistance and patient authority-introduction to
      paper IX: integrative psychodynamic treatment of psychotic disorders.

PMID- 19113964
TI  - A view from Riggs: treatment resistance and patient authority-IX. Integrative
      psychodynamic treatment of psychotic disorders.
AB  - Psychotic spectrum disorders present treatment challenges for patients, families,
      and clinicians. This article addresses the history of the dualism in the field
      between biological and psychological approaches to mental disorders, and surveys
      the contemporary literature about the etiology and treatment of psychotic
      spectrum disorders. An integrative approach to treatment derived from work at
      Austen Riggs with previously treatment refractory patients with psychotic
      spectrum disorders is described that combines individual psycho- dynamic
      psychotherapy, psychopharmacology, family systems approaches, and intensive
      psychosocial engagement. Helping patients develop their own authority to join the
      treatment, use relationships for learning, and understand the meaning of their
      symptoms is central to the treatment at Austen Riggs. An extended case vignette
      of a patient diagnosed with a schizoaffective disorder is presented illustrating
      this integrative psychodynamic treatment approach.

PMID- 19113966
TI  - Hybrid solar cells from P3HT and silicon nanocrystals.
AB  - We are reporting new hybrid solar cells based on blends of silicon nanocrystals
      (Si NCs) and poly-3(hexylthiophene) (P3HT) polymer in which a percolating network
      of the nanocrystals acts as the electron-conducting phase. The properties of
      composite Si NCs/P3HT devices made by spin-coating Si NCs and P3HT from a common
      solvent were studied as a function of Si NC size and Si NC/P3HT ratio. The open
      circuit voltage and short-circuit current are observed to depend on the Si NC
      size due to changes in the bandgap and surface-area-to-volume ratio. Under
      simulated one-sun A.M. 1.5 direct illumination (100 mW/cm2), devices made with 35
      wt % Si NCs 3-5 nm in size showed 1.15% power conversion efficiency.

PMID- 19113967
TI  - Substrate promiscuity of the cyclic dipeptide prenyltransferases from Aspergillus
      fumigatus ( section sign).
AB  - This study reports that a series of tryptophan derivatives with modifications on
      the side chain or at the indole ring were accepted by two cyclic dipeptide
      prenyltransferases, CdpNPT and FtmPT1, and converted to prenylated derivatives.
      The structures of the enzymatic products were elucidated by NMR and MS analyses.
      In comparison to cyclic dipeptides, which were reversely prenylated by CdpNPT at
      N-1 and in a regular manner by FtmPT1 at C-2, respectively, tryptophan and its
      simple derivatives were prenylated reversely by both enzymes at N-1. These
      results demonstrated the substrate promiscuity of both enzymes.

PMID- 19113968
TI  - Prenylated and benzylated flavonoids from the fruits of Cudrania tricuspidata.
AB  - Three new prenylated isoflavones, 5,7-dihydroxy-6-(2''-hydroxy-3''-methylbut-3''
      enyl)-4'-methoxylisoflavone (1), 5,4'-dihydroxy-6-(3''-methylbut-2''-enyl)-2'''
      (4'''-hydroxy-4'''-methylethyl)-3'''-methoxydihydrofurano
      [4''',5''';7,8]isoflavone (2), and 5,4'-dihydroxy-8-(3''-methylbut-2''-enyl)-2'''
      (4'''-hydroxy-4'''-methylethyl)furano-[4''',5''';6,7]isoflavone (3), a benzylated
      dihydroflavonol, 5,7,4'-trihydroxy-8-p-hydroxybenzyldihydroflavonol (4), and
      eight known flavonoids (5-12) were isolated from the fruits of Cudrania
      tricuspidata. The structures of these compounds were determined on the basis of
      MS and (1)H and (13)C NMR spectroscopic data, including 2D NMR experiments.
      Compounds 2, 3, 6, 7, 8, 10, 11, and 12 inhibited LPS-induced nitric oxide
      production, with IC(50) values of 11.8-41.8 microM.

PMID- 19113969
TI  - Bioassay-guided isolation of xanthones and polycyclic prenylated
      acylphloroglucinols from Garcinia oblongifolia.
AB  - Bioassay-guided fractionation of the acetone extract of the bark of Garcinia
      oblongifolia has resulted in the isolation of three new xanthones,
      oblongixanthones A-C (1-3), three new polyprenylated benzoylphloroglucinols,
      oblongifolins E-G (4-6), and 12 known compounds. Oblongifolins I (5) and J (6)
      are the first natural products that have similar structural features to those of
      two known oxidation products of garcinol. The structures of the new compounds 1-6
      were characterized by spectroscopic data interpretation. All isolates were
      assayed for their apoptosis-inducing effects against HeLa-C3 cells. Oblongifolin
      C (16) was found to be the most potent apoptotic inducer of the compounds
      evaluated.

PMID- 19113970
TI  - The radical nature of combined psychotherapy.
AB  - Abstract The therapist's commitment in thought and action to combined practice
      influences all aspects of professional life. Hence, the "radical" (or
      foundational): The idea as well as the shared history of combined psychotherapy
      are rooted within the complexities and intensities of the multiple transference
      countertransferences, intrapsychic defenses, interpersonal strategies, and
      inevitable enactments of all members of one's practice. Case anecdotes illustrate
      (a) the psycho-social impact of Establishment psychoanalysis and group analysis
      on the therapist; (b) the intertwining of dyadic-group experience on manifest and
      latent content, inference making, and interpretation; (c) how the "group" never
      leaves the room, that is, the salutary effects on the therapist's thinking and
      clinical relationships of the idea as well as the reality of group, even with
      those patients not exposed to combined treatment; and (d) resistances specific to
      combined treatment. Combined individual-group psychoanalytic therapy is a natural
      fit, yet a radical extension of contemporary relational psychoanalytic theory and
      practice.

PMID- 19113971
TI  - Transference in combined individual and group psychotherapy.
AB  - Abstract The value of combined individual and group therapy is considered, with a
      focus on dealing with resistance, illuminating the transference process, and
      making that process accessible to analysis. The ways in which the two modalities
      enhance each other's assets and compensate for each other's limitations are
      explored.

PMID- 19113972
TI  - Some problems with treatment: destructive enactments in combined therapy.
AB  - Abstract The aim and hope of combined therapy is that the arrangement of group
      and individual treatment affords greater therapeutic effect because of its
      psychic interactions. For some patients, the modalities together may lead to
      promising, if often complex, analysis through an open flow of information between
      the two modalities. However, the two cases I present illustrate problems that may
      arise in combined treatment. In these two cases, the interaction between the
      modalities may have prevented important working through and caused an irreparable
      breach in the therapeutic alliance. The interdependence among complex enactments,
      my countertransference, and the respective groups' transferences was emotionally
      complex. In this paper I describe various forms of these enactments, explore some
      ideas about why enactments occurred, and discuss their impact on the treatment of
      these patients.

PMID- 19113973
TI  - The necessity of combined therapy in the treatment of shame: a case report.
AB  - Abstract In some situations, combined psychotherapy may not be merely a choice,
      but a necessity for successful treatment. I present a case report of a
      hospitalized Vietnam veteran who had sexually abused one of his daughters. In
      individual therapy, the patient learned to speak about himself, his significant
      guilt, and his shame, in a trusting environment. After a year of outpatient
      individual work, I felt that the addition of group psychotherapy would help this
      withdrawn man to connect to a social milieu. Although anxious about self
      disclosure and confidentiality, he joined a heterogeneous veterans' group, and
      came to reveal his secrets there. While he continued to use the individual
      sessions to broach painful issues, the group served to uncover material that had
      not emerged otherwise. The acceptance he experienced in the group expanded and
      cemented gains made in the dyad, which in turn made the ongoing group experience
      tolerable. His self-exposure and efforts at bonding and reparation catalyzed
      therapeutic movement for other members as well. The two modalities served to
      reinforce and make more powerful the effects of each. Therapeutic progress
      depended on the combined treatment-both were necessary, neither was sufficient.

PMID- 19113974
TI  - The synergy of group and individual treatment modalities in the aftermath of
      disaster and unfolding trauma.
AB  - Abstract Recognizing disasters as traumatizing events that unfold with
      devastating physical and psychological sequalae, the author considers the
      interplay of individual and group treatment modalities in facilitating
      progression throughout stages of recovery. The stages-safety, remembering and
      mourning, and reconnection-are recognized as interrelated recovery processes that
      occur concurrently as well as sequentially throughout the treatment process.
      Drawing upon her 9/11 work with civilian and uniformed populations, the author
      describes the way in which group and individual therapies-whether conducted
      consecutively or concurrently, as single session, short-term, or long-term
      programs-work synergistically to foster recovery.

PMID- 19113975
TI  - The integration of relationship-focused group therapy with couples treatment.
AB  - Abstract This article discusses a new treatment paradigm combining couples
      therapy with a separate relationship-focused group therapy for each partner. This
      model is thought to be especially efficacious for those couples experiencing
      difficulty in making progress in couples treatment alone. The authors postulate
      that the addition of a separate group process utilizing object relations and self
      psycho- logical theories, as well as concepts borrowed from Imago relationship
      therapy, enhance the probability of working through intractable transference
      projections that tend to be impervious to either treatment modality on its own.
      Challenges created by this combined approach as well as benefits are addressed.
      Theoretical rationale and treatment implications are discussed.

PMID- 19113976
TI  - Ethical hot spots of combined individual and group therapy: applying four ethical
      systems.
AB  - Abstract Combined therapy presents ethical quandaries that occur in individual
      psychotherapy and group psychotherapy, and dilemmas specifically associated with
      their integration. This paper examines two types of ethical frameworks (a
      classical principle-based framework and a set of context-based frameworks) for
      addressing the ethical hot spots of combined therapy: self-referral, transfer of
      information, and termination. The principle-based approach enables the
      practitioner to see what core values may be served or violated by different
      courses of action in combined therapy dilemmas. Yet, the therapist is more likely
      to do justice to the complexity and richness of the combined therapy situation by
      supplementing a principle analysis with three additional ethical frameworks.
      These approaches are: virtue ethics, feminist ethics, and casuistry. An analysis
      of three vignettes illustrates how these contrasting ethical models not only
      expand the range of features to which the therapist attends but also the array of
      solutions the therapist generates.

PMID- 19113977
TI  - On the vicissitudes of combining individual and group psychotherapy.
AB  - Abstract Reviewing a series of articles in this special issue on combined
      treatment incorporating individual and group therapy, and in one instance couples
      therapy and a relationship group, the author provides a synoptic history of
      combined treatment, noting that the relational perspectives of psychoanalysis and
      systems theories of groups now provide conceptual frameworks for combined
      therapies. Taking up each article in turn, he considers that combined treatment
      poses particular problems while having certain advantages. He discusses the
      theoretical emphases and biases of each article, whether relational psychology,
      classical psychoanalysis, object relations theory, or self-psychology. He
      considers the roles of transference and countertransference, patient-therapist
      enactments, empathic attunement, "surrogate therapy" by the group members, and
      ethics in determining outcomes. In addition, the author notes how so-called
      difficult or regressed patients impact upon and are affected by the use of
      combined therapy modalities.

PMID- 19113978
TI  - Development of a panel of well-characterized human immunodeficiency virus type 1
      isolates from newly diagnosed patients including acute and recent infections.
AB  - The aim of this study was the development of a panel constituted by well-defined
      HIV-1 strains of different genetic forms, with a particular focus on isolates
      from acute and recent infections. Fourteen HIV-1 isolates, including four from
      acute and five from recent infections, were expanded in peripheral blood
      mononuclear cells. SI phenotype, coreceptors use, and TCID(50)/ml were
      determined. V3 net charge was calculated. Near full-length genomes were amplified
      by RT-nested PCR in four overlapping segments. Phylogenetic analyses were
      performed with neighbor-joining trees and bootscanning. Analysis of cysteine
      residues, lengths of variable regions, and potential N-linked glycosylation sites
      in gp120 and gp41 was performed. Viral stocks were produced. Thirteen strains
      were NSI/R5 and one SI/R5,X4. TCID(50)/ml ranged between 10(4.6) and 10(6). V3
      net charge was <+5 in 12 sequences and +5 in two sequences. Near full-length HIV
      1 genomes analysis identified viruses of the following genetic forms: eight
      subtype B, three subtype C, two CRF02_AG, and one subtype G. Cysteine residues
      that form the V1,V2,V3, and V4 loops were highly conserved. The number of
      potential N-linked glycosylation sites in gp120 and gp41 ranged between 24-29 and
      4-6, respectively. Seven potential N-linked glycosylation sites in gp120 and
      three in gp41 were conserved. V1, V2, V4, and V5 variable regions exhibited
      substantial length variation. In addition, an analysis of transmitted and natural
      resistance to current antiretroviral drugs in these strains was performed. It is
      worth mentioning that the 13S mutation in the V3 sequence, associated with
      resistance to maraviroc, was observed in a subtype B strain that harbored
      resistance mutations to nucleoside reverse transcriptase inhibitors and to T20.
      The availability of a panel including strains from acute and recent infections
      should be a valuable resource for optimizing and standardizing vaccine candidate
      assessment. Near full-length genome characterization may be necessary for
      evaluating clade-specific reactivities.

PMID- 19113979
TI  - Synthesis, oxidant properties, and antitumoral effects of a heteroleptic
      palladium(II) complex of curcumin on human prostate cancer cells.
AB  - A new ionic Pd(II) complex, [(bipy)Pd(Pcurc)][CF(3)SO(3)], 1, with the metal
      center coordinated to two different chelating ligands, the pure curcumin (Pcurc)
      and the 4,4'-dinonyl-2,2'-bipyridine (bipy), has been synthesized, fully
      characterized, and its antitumoral mechanism and oxidant property have been
      investigated. The Pd(II) complex induces both cell growth inhibition and
      apoptosis of human prostate cancer cells, (LnCaP, PC3, and DU145) through the
      production of ROS and JNK phosphorylation associated with GSTp1 down-regulation.
      ROS production induced by complex 1 treatment activated apoptosis through
      mitochondrial membrane depolarization in all prostate cancer cells, with up
      regulation of Bax and down-regulation of Bcl-2 proteins. In addition, while
      curcumin determines DNA damage and PARP cleavage, complex 1 does not elicit any
      activation of PARP enzyme. Taken together, these data validate the significance
      of curcumin complexation to a metal center and its conjugation to another
      functionalized bioactive ligand in the apoptosis signal transduction and
      enhancement of cell death in prostate cancer cell lines and suggest the potential
      of this design strategy in the improvement of the metal-based drugs cytotoxicity.

PMID- 19113983
TI  - Refractory diarrhea in a patient with HIV infection.

PMID- 19113985
TI  - Persistent, undetected Trichomonas vaginalis infections?

PMID- 19113986
TI  - Detection of HIV type 1 load by the Roche Cobas TaqMan assay in patients with
      viral loads previously undetectable by the Roche Cobas Amplicor Monitor.

PMID- 19113987
TI  - Use of active surveillance cultures in intensive care units.

PMID- 19113988
TI  - Persistence of mumps antibodies after 2 doses of measles-mumps-rubella vaccine.
AB  - BACKGROUND: Since 1990, most US schoolchildren have received a second dose of
      measles-mumps-rubella vaccine (MMR2) at kindergarten entry. The objective of the
      present study was to evaluate the short- and long-term mumps immunogenicity of
      MMR2. METHODS: At enrollment in 1994-1995, children (n=308) in a rural Wisconsin
      health maintenance organization received MMR2 at age 4-6 years. A comparison
      group of older children (n=308) was vaccinated at age 9-11 years. Serum samples
      were collected over 12 years. Mumps antibody levels were evaluated by plaque
      reduction neutralization (lowest detectable titer, 10). RESULTS: Before MMR2, the
      geometric mean titer (GMT) for the younger group was 33; no subject was
      seronegative, but 16% had the lowest detectable titer. In response to MMR2, the
      GMT tripled to 97, and the proportion with low titers diminished to 3%. Four-fold
      boosts occurred among 54%, but only 3% were positive for immunoglobulin M. Twelve
      years after MMR2, the GMT declined to 46, the proportion with titers<or=10 was
      not significantly different from the pre-MMR2 proportion, and 5% were
      seronegative. The older group showed similar patterns, and at age 17 years both
      groups had comparable antibody levels. CONCLUSIONS: The mumps antibody response
      to MMR2 was vigorous, but over a 12-year period titers declined to levels similar
      to pre-MMR2 titers. No advantage was apparent in delaying MMR2 from kindergarten
      to middle school.

PMID- 19113990
TI  - Tracking of leisure-time physical activity during adolescence and young
      adulthood: a 10-year longitudinal study.
AB  - BACKGROUND: The purpose of this study was to show how participation in leisure
      time physical activity changes between ages 13 to 23, and to what extent engaging
      in specific types of sports tracks into young adulthood. METHODS: The sample
      comprised 630 subjects who responded to questionnaires at age 13, with seven
      follow-ups over a 10-year period in the Norwegian Longitudinal Health Behaviour
      Study. The associations between adolescent participation in global and specific
      types of leisure-time physical activity were examined by analyses of variance,
      regression analysis and growth curve analysis. RESULTS: The findings suggest that
      the transition from adolescence to adulthood is, on average, a period of decline
      in physical activity, but with the decline levelling off into adulthood. The
      decline was significantly greater among males than females. There were
      substantial individual differences in the amount of change, in particular among
      males.Jogging alone and cycling, recreational activities such as skiing and
      hiking, and ball games, showed a high degree of tracking from age 15 to 23.The
      findings indicate low associations between participation in specific types of
      activities during adolescence and global leisure-time physical activity in young
      adulthood, while participation in several adolescent physical activities
      simultaneously was moderately related to later activity. Thus, being involved in
      various types of physical activity may offer good opportunities for establishing
      lifelong involvement in physical activity, independent of the specific type of
      activity. CONCLUSION: The observed variation in change might suggest a need for a
      more targeted approach, with a focus on subgroups of individuals. The group of
      inactive youth may be considered as a high risk group, and the findings suggest
      that adolescent males who are inactive early seem likely to continue to be
      inactive later.The observed heterogeneity in change highlights the limitation of
      previous approaches to analyzing physical levels over time, and suggests that
      multilevel analysis should be used in future research on longitudinal data on
      physical activity.

PMID- 19113989
TI  - Treatment with protein synthesis inhibitors improves outcomes of secondary
      bacterial pneumonia after influenza.
AB  - Pneumonia occurring as a secondary infection after influenza is a major cause of
      excess morbidity and mortality, despite the availability and use of antibiotics
      active against Streptococcus pneumoniae. We hypothesized that the use of a
      bacteriostatic protein synthesis inhibitor would improve outcomes by reducing the
      inflammatory response. BALB/cJ mice infected with influenza virus and
      superinfected with S. pneumoniae were treated with either the cell-wall-active
      antibiotic ampicillin or the protein synthesis inhibitor clindamycin or
      azithromycin. In the model, ampicillin therapy performed significantly worse
      (survival rate, 56%) than (1) clindamycin therapy used either alone (82%) or in
      combination with ampicillin (80%) and (2) azithromycin (92%). Improved survival
      appeared to be mediated by decreased inflammation manifested as lower levels of
      inflammatory cells and proinflammatory cytokines in the lungs and by observation
      of less-severe histopathologic findings. These data suggest that beta-lactam
      therapy may not be optimal as a first-line treatment for community-acquired
      pneumonia when it follows influenza.

PMID- 19113991
TI  - Reconsidering the generation time hypothesis based on nuclear ribosomal ITS
      sequence comparisons in annual and perennial angiosperms.
AB  - BACKGROUND: Differences in plant annual/perennial habit are hypothesized to cause
      a generation time effect on divergence rates. Previous studies that compared
      rates of divergence for internal transcribed spacer (ITS1 and ITS2) sequences of
      nuclear ribosomal DNA (nrDNA) in angiosperms have reached contradictory
      conclusions about whether differences in generation times (or other life history
      features) are associated with divergence rate heterogeneity. We compared
      annual/perennial ITS divergence rates using published sequence data, employing
      sampling criteria to control for possible artifacts that might obscure any actual
      rate variation caused by annual/perennial differences. RESULTS: Relative rate
      tests employing ITS sequences from 16 phylogenetically-independent
      annual/perennial species pairs rejected rate homogeneity in only a few
      comparisons, with annuals more frequently exhibiting faster substitution rates.
      Treating branch length differences categorically (annual faster or perennial
      faster regardless of magnitude) with a sign test often indicated an excess of
      annuals with faster substitution rates. Annuals showed an approximately 1.6-fold
      rate acceleration in nucleotide substitution models for ITS. Relative rates of
      three nuclear loci and two chloroplast regions for the annual Arabidopsis
      thaliana compared with two closely related Arabidopsis perennials indicated that
      divergence was faster for the annual. In contrast, A. thaliana ITS divergence
      rates were sometimes faster and sometimes slower than the perennial. In
      simulations, divergence rate differences of at least 3.5-fold were required to
      reject rate constancy in > 80 % of replicates using a nucleotide substitution
      model observed for the combination of ITS1 and ITS2. Simulations also showed that
      categorical treatment of branch length differences detected rate heterogeneity >
      80% of the time with a 1.5-fold or greater rate difference. CONCLUSION: Although
      rate homogeneity was not rejected in many comparisons, in cases of significant
      rate heterogeneity annuals frequently exhibited faster substitution rates. Our
      results suggest that annual taxa may exhibit a less than 2-fold rate acceleration
      at ITS. Since the rate difference is small and ITS lacks statistical power to
      reject rate homogeneity, further studies with greater power will be required to
      adequately test the hypothesis that annual and perennial plants have
      heterogeneous substitution rates. Arabidopsis sequence data suggest that relative
      rate tests based on multiple loci may be able to distinguish a weak acceleration
      in annual plants. The failure to detect rate heterogeneity with ITS in past
      studies may be largely a product of low statistical power.

PMID- 19113992
TI  - Targeting cyclin B1 inhibits proliferation and sensitizes breast cancer cells to
      taxol.
AB  - BACKGROUND: Cyclin B1, the regulatory subunit of cyclin-dependent kinase 1
      (Cdk1), is essential for the transition from G2 phase to mitosis. Cyclin B1 is
      very often found to be overexpressed in primary breast and cervical cancer cells
      as well as in cancer cell lines. Its expression is correlated with the malignancy
      of gynecological cancers. METHODS: In order to explore cyclin B1 as a potential
      target for gynecological cancer therapy, we studied the effect of small
      interfering RNA (siRNA) on different gynecological cancer cell lines by
      monitoring their proliferation rate, cell cycle profile, protein expression and
      activity, apoptosis induction and colony formation. Tumor formation in vivo was
      examined using mouse xenograft models. RESULTS: Downregulation of cyclin B1
      inhibited proliferation of several breast and cervical cancer cell lines
      including MCF-7, BT-474, SK-BR-3, MDA-MB-231 and HeLa. After combining cyclin B1
      siRNA with taxol, we observed an increased apoptotic rate accompanied by an
      enhanced antiproliferative effect in breast cancer cells. Furthermore, control
      HeLa cells were progressively growing, whereas the tumor growth of HeLa cells pre
      treated with cyclin B1 siRNA was strongly inhibited in nude mice, indicating that
      cyclin B1 is indispensable for tumor growth in vivo. CONCLUSION: Our data support
      the notion of cyclin B1 being essential for survival and proliferation of
      gynecological cancer cells. Concordantly, knockdown of cyclin B1 inhibits
      proliferation in vitro as well as in vivo. Moreover, targeting cyclin B1
      sensitizes breast cancer cells to taxol, suggesting that specific cyclin B1
      targeting is an attractive strategy for the combination with conventionally used
      agents in gynecological cancer therapy.

PMID- 19113993
TI  - High prevalence of obesity, central obesity and abnormal glucose tolerance in the
      middle-aged Finnish population.
AB  - BACKGROUND: There is a worldwide increase in the prevalence of obesity and
      disturbances in glucose metabolism. The aim of this study was to assess the
      current prevalence of obesity, central obesity and abnormal glucose tolerance in
      Finnish population, and to investigate the associations between body mass index
      (BMI), waist circumference and abnormal glucose tolerance. METHODS: A cross
      sectional population-based survey was conducted in Finland during October 2004
      and January 2005. A total of 4500 randomly selected individuals aged 45-74 years
      were invited to a health examination that included an oral glucose tolerance
      test. The participation rate was 62% in men and 67% in women. RESULTS: The
      prevalence of obesity was 23.5% (95% Confidence Interval (CI) 21.1-25.9) in men,
      and 28.0% (95% CI 25.5-30.5) in women. The overall prevalence of abnormal glucose
      tolerance (including type 2 diabetes, impaired glucose tolerance, or impaired
      fasting glucose) was 42.0% (95% CI 39.2-44.8) in men and 33.4% (95% CI 30.9-36.0)
      in women. The prevalence of previously unknown, screen-detected type 2 diabetes
      was 9.3% (95% CI 7.7-11.0) in men and 7.3% (95% CI 5.9-8.7) in women. Central
      obesity was associated with abnormal glucose tolerance within each of the three
      BMI categories normal (< 25 kg/m2), overweight (25-29 kg/m2), and obese (>or= 30
      kg/m2). CONCLUSION: In a population-based random sample of Finnish population,
      prevalences of obesity, central obesity and abnormal glucose tolerance were found
      to be high. A remarkably high number of previously undetected cases of type 2
      diabetes was detected. Waist circumference is a predictor of abnormal glucose
      tolerance in all categories of obesity.

PMID- 19113994
TI  - Miller Early Childhood Sustained Home-visiting (MECSH) trial: design, method and
      sample description.
AB  - BACKGROUND: Home visiting programs comprising intensive and sustained visits by
      professionals (usually nurses) over the first two years of life show promise in
      promoting child health and family functioning, and ameliorating disadvantage.
      Australian evidence of the effectiveness of sustained nurse home visiting in
      early childhood is limited. This paper describes the method and cohort
      characteristics of the first Australian study of sustained home visiting
      commencing antenatally and continuing to child-age two years for at-risk mothers
      in a disadvantaged community (the Miller Early Childhood Sustained Home-visiting
      trial). METHODS AND DESIGN: Mothers reporting risks for poorer parenting outcomes
      residing in an area of socioeconomic disadvantage were recruited between February
      2003 and March 2005. Mothers randomised to the intervention group received a
      standardised program of nurse home visiting. Interviews and observations covering
      child, maternal, family and environmental issues were undertaken with mothers
      antenatally and at 1, 12 and 24 months postpartum. Standardised tests of child
      development and maternal-child interaction were undertaken at 18 and 30 months
      postpartum. Information from hospital and community heath records was also
      obtained. DISCUSSION: A total of 338 women were identified and invited to
      participate, and 208 were recruited to the study. Rates of active follow-up were
      86% at 12 months, 74% at 24 months and 63% at 30 months postpartum. Participation
      in particular data points ranged from 66% at 1 month to 51% at 24 months
      postpartum. Rates of active follow-up and data point participation were not
      significantly different for the intervention or comparison group at any data
      point. Mothers who presented for antenatal care prior to 20 weeks pregnant, those
      with household income from full-time employment and those who reported being
      abused themselves as a child were more likely to be retained in the study. The
      Miller Early Childhood Sustained Home-visiting trial will provide Australian
      evidence of the effectiveness of sustained nurse home visiting for children at
      risk of poorer health and developmental outcomes. TRIAL REGISTRATION:
      ACTRN12608000473369.

PMID- 19113995
TI  - Single-chain Fv phage display propensity exhibits strong positive correlation
      with overall expression levels.
AB  - BACKGROUND: Single chain Fvs (scFvs) are widely applied in research, diagnostics
      and therapeutic settings. Display and selection from combinatorial libraries is
      the main route to their discovery and many factors influence the success of this
      process. They exhibit low thermodynamic stability, resulting in low levels of
      premature cytosolic folding or aggregation which facilitates sec YEG-mediated
      translocation and phage in E. coli. However, there is little data analysing how
      this is related to and influenced by scFv protein expression. RESULTS: We
      characterised the relationship between overall scFv expression and display
      propensity for a panel of 15 anti-tetanus toxin scFvs and found a strong positive
      correlation (Rho = 0.88, p < 0.005) between the two parameters. Display
      propensity, overall expression and soluble localisation to the periplasm and
      extracellular fractions were clone specific characteristics which varied despite
      high levels of sequence homology. There was no correlation between display of
      scFv or its expression in non-fused (free) form with soluble scFv localisation to
      the periplasm or culture supernatant. This suggests that divergence in the fate
      of scFv-pIII and non-fused scFv after translocation to the periplasm accounts for
      the observed disparity. Differential degrees of periplasmic aggregation of non
      fused scFv between clones may affect the partitioning of scFv in the periplasm
      and culture supernatant abrogating any correlation. We suggest that these factors
      do not apply to the scFv-pIII fusion since it remains anchored to the bacterial
      inner membrane as part of the innate phage packaging and budding process.
      CONCLUSION: We conclude that in the absence of premature cytosolic aggregation or
      folding, the propensity of a scFv to be displayed on phage is directly related to
      its overall expression level and is thus indirectly influenced by factors such as
      codon bias, mRNA abundance or putative DNA motifs affecting expression. This
      suggests that scFvs capable of high overall expression and display levels may not
      produce high yields of non phage-fused soluble protein in either the periplasmic
      or extracellular fractions of E. coli. This should be considered when screening
      clones selected from combinatorial libraries for further study.

PMID- 19113996
TI  - Standardisation of rates using logistic regression: a comparison with the direct
      method.
AB  - BACKGROUND: Standardisation of rates in health services research is generally
      undertaken using the direct and indirect arithmetic methods. These methods can
      produce unreliable estimates when the calculations are based on small numbers.
      Regression based methods are available but are rarely applied in practice. This
      study demonstrates the advantages of using logistic regression to obtain smoothed
      standardised estimates of the prevalence of rare disease in the presence of
      covariates. METHODS: Step by step worked examples of the logistic and direct
      methods are presented utilising data from BETS, an observational study designed
      to estimate the prevalence of subclinical thyroid disease in the elderly. Rates
      calculated by the direct method were standardised by sex and age categories,
      whereas rates by the logistic method were standardised by sex and age as a
      continuous variable. RESULTS: The two methods produce estimates of similar
      magnitude when standardising by age and sex. The standard errors produced by the
      logistic method were lower than the conventional direct method. CONCLUSION:
      Regression based standardisation is a practical alternative to the direct method.
      It produces more reliable estimates than the direct or indirect method when the
      calculations are based on small numbers. It has greater flexibility in factor
      selection and allows standardisation by both continuous and categorical
      variables. It therefore allows standardisation to be performed in situations
      where the direct method would give unreliable results.

PMID- 19113997
TI  - EST based phylogenomics of Syndermata questions monophyly of Eurotatoria.
AB  - BACKGROUND: The metazoan taxon Syndermata comprising Rotifera (in the classical
      sense of Monogononta+Bdelloidea+Seisonidea) and Acanthocephala has raised several
      hypotheses connected to the phylogeny of these animal groups and the included
      subtaxa. While the monophyletic origin of Syndermata and Acanthocephala is well
      established based on morphological and molecular data, the phylogenetic position
      of Syndermata within Spiralia, the monophyletic origin of Monogononta,
      Bdelloidea, and Seisonidea and the acanthocephalan sister group are still a
      matter of debate. The comparison of the alternative hypotheses suggests that
      testing the phylogenetic validity of Eurotatoria (Monogononta+Bdelloidea) is the
      key to unravel the phylogenetic relations within Syndermata. The syndermatan
      phylogeny in turn is a prerequisite for reconstructing the evolution of the
      acanthocephalan endoparasitism. RESULTS: Here we present our results from a
      phylogenomic approach studying i) the phylogenetic position of Syndermata within
      Spiralia, ii) the monophyletic origin of monogononts and bdelloids and iii) the
      phylogenetic relations of the latter two taxa to acanthocephalans. For this
      analysis we have generated EST libraries of Pomphorhynchus laevis, Echinorhynchus
      truttae (Acanthocephala) and Brachionus plicatilis (Monogononta). By extending
      these data with database entries of B. plicatilis, Philodina roseola (Bdelloidea)
      and 25 additional metazoan species, we conducted phylogenetic reconstructions
      based on 79 ribosomal proteins using maximum likelihood and bayesian approaches.
      Our findings suggest that the phylogenetic position of Syndermata within Spiralia
      is close to Platyhelminthes, that Eurotatoria are not monophyletic and that
      bdelloids are more closely related to acanthocephalans than monogononts.
      CONCLUSION: Mapping morphological character evolution onto molecular phylogeny
      suggests the (partial or complete) reduction of the corona and the emergence of a
      retractable anterior end (rostrum, proboscis) before the separation of
      Acanthocephala. In particular, the evolution of a rostrum might have been a key
      event leading to the later evolution of the acanthocephalan endoparasitism, given
      the enormous relevance of the proboscis for anchoring of the adults to the
      definitive hosts' intestinal wall.

PMID- 19113998
TI  - Dynamic splinting for knee flexion contracture following total knee arthroplasty:
      a case report.
AB  - Total Knee Arthroplasty operations are increasing in frequency, and knee flexion
      contracture is a common pathology, both pre-existing and post-operative. A 61
      year-old male presented with knee flexion contracture following a total knee
      arthroplasty. Physical therapy alone did not fully reduce the contracture and
      dynamic splinting was then prescribed for daily low-load, prolonged-duration
      stretch. After 28 physical therapy sessions, the active range of motion improved
      from -20 degrees to -12 degrees (stiff knee still lacking full extension), and
      after eight additional weeks with nightly wear of dynamic splint, the patient
      regained full knee extension, (active extension improved from -12 degrees to 0
      degrees ).

PMID- 19113999
TI  - Use of complementary and alternative medicines for children with chronic health
      conditions in Lagos, Nigeria.
AB  - BACKGROUND: The use of complementary and alternative medicine (CAM) is on the
      increase globally with a high prevalence in children and adults with chronic
      illnesses. Many studies have evaluated the epidemiology of medicine use for
      children in developing countries but none has evaluated the use of CAM for
      children with chronic illnesses. The aim of this study was therefore to determine
      the prevalence, pattern of use, parental sources of information, perceived
      benefits, cost, and adverse effects of CAM in children with epilepsy, sickle cell
      anaemia and asthma in Lagos, Nigeria. METHODS: Parents of children with epilepsy
      (122), asthma (78) or sickle cell anaemia (118) who presented consecutively to
      the paediatric neurology, respiratory and haematology clinics of the Lagos State
      University Teaching Hospital (LASUTH), Ikeja were interviewed with a structured
      open- and close-ended questionnaire. The information obtained comprised the
      demography of both the patients and their parents; past and present treatments
      received by the patients; the type of CAM, if any, used by the patients; and the
      sources, cost, benefits and adverse effects of the CAM used. RESULTS: A total of
      303 CAMs were used by the patients, either alone or in combination witother CAM.
      CAM was reportedly used by 99 (31%) patients (epilepsy--38%, sickle cell anaemia-
      36% and asthma--25%). The majority (84%) of these patients were currently using
      CAM. The use of CAM was stopped six months prior to the study by 16 patients
      (16%). Biological products were the most frequently used CAMs (58%), followed by
      alternative medical systems (27%) and mind-body interventions (14%). Relations,
      friends and neighbours had a marked influence on 76% of the parents who used CAM
      for their children. Eighty-five (86%) parents were willing to discuss the use of
      CAM with their doctors but were not asked. CAM use was associated with adverse
      reactions in 7.1% of the patients. CONCLUSION: Parental use of CAMs to treat
      their children with epilepsy, asthma and sickle cell anaemia is common in
      Nigeria. Efforts should be made by doctors taking care of these patients to
      identify those CAM therapies that are beneficial, harmless and cheap for possible
      integration with conventional therapy.

PMID- 19114001
TI  - SPRINT: a new parallel framework for R.
AB  - BACKGROUND: Microarray analysis allows the simultaneous measurement of thousands
      to millions of genes or sequences across tens to thousands of different samples.
      The analysis of the resulting data tests the limits of existing bioinformatics
      computing infrastructure. A solution to this issue is to use High Performance
      Computing (HPC) systems, which contain many processors and more memory than
      desktop computer systems. Many biostatisticians use R to process the data gleaned
      from microarray analysis and there is even a dedicated group of packages,
      Bioconductor, for this purpose. However, to exploit HPC systems, R must be able
      to utilise the multiple processors available on these systems. There are existing
      modules that enable R to use multiple processors, but these are either difficult
      to use for the HPC novice or cannot be used to solve certain classes of problems.
      A method of exploiting HPC systems, using R, but without recourse to mastering
      parallel programming paradigms is therefore necessary to analyse genomic data to
      its fullest. RESULTS: We have designed and built a prototype framework that
      allows the addition of parallelised functions to R to enable the easy
      exploitation of HPC systems. The Simple Parallel R INTerface (SPRINT) is a
      wrapper around such parallelised functions. Their use requires very little
      modification to existing sequential R scripts and no expertise in parallel
      computing. As an example we created a function that carries out the computation
      of a pairwise calculated correlation matrix. This performs well with SPRINT. When
      executed using SPRINT on an HPC resource of eight processors this computation
      reduces by more than three times the time R takes to complete it on one
      processor. CONCLUSION: SPRINT allows the biostatistician to concentrate on the
      research problems rather than the computation, while still allowing exploitation
      of HPC systems. It is easy to use and with further development will become more
      useful as more functions are added to the framework.

PMID- 19114002
TI  - Fish communities in coastal freshwater ecosystems: the role of the physical and
      chemical setting.
AB  - BACKGROUND: We explored how embayment watershed inputs, morphometry, and
      hydrology influence fish community structure among eight embayments located along
      the southeastern shoreline of Lake Ontario, New York, USA. Embayments differed in
      surface area and depth, varied in their connections to Lake Ontario and their
      watersheds, and drained watersheds representing a gradient of agricultural to
      forested land use. RESULTS: We related various physicochemical factors, including
      total phosphorus load, embayment area, and submerged vegetation, to differences
      in fish species diversity and community relative abundance, biomass, and size
      structure both among and within embayments. Yellow perch (Perca flavescens) and
      centrarchids numerically dominated most embayment fish communities. Biomass was
      dominated by piscivorous fishes including brown bullhead (Ameiurus nebulosus),
      bowfin (Amia calva), and northern pike (Esox lucius). Phosphorus loading
      influenced relative biomass, but not species diversity or relative abundance.
      Fish relative abundance differed among embayments; within embayments, fish
      abundance at individual sampling stations increased significantly with submerged
      vegetative cover. Relative biomass differed among embayments and was positively
      related to total phophorus loading and embayment area. Fish community size
      structure, based on size spectra analysis, differed among embayments, with the
      frequency of smaller-bodied fishes positively related to percent vegetation.
      CONCLUSION: The importance of total phosphorus loading and vegetation in
      structuring fish communities has implications for anthropogenic impacts to
      embayment fish communities through activities such as farming and residential
      development, reduction of cultural eutrophication, and shoreline development and
      maintenance.

PMID- 19114000
TI  - Quantification of SLIT-ROBO transcripts in hepatocellular carcinoma reveals two
      groups of genes with coordinate expression.
AB  - BACKGROUND: SLIT-ROBO families of proteins mediate axon pathfinding and their
      expression is not solely confined to nervous system. Aberrant expression of SLIT
      ROBO genes was repeatedly shown in a wide variety of cancers, yet data about
      their collective behavior in hepatocellular carcinoma (HCC) is missing. Hence, we
      quantified SLIT-ROBO transcripts in HCC cell lines, and in normal and tumor
      tissues from liver. METHODS: Expression of SLIT-ROBO family members was
      quantified by real-time qRT-PCR in 14 HCC cell lines, 8 normal and 35 tumor
      tissues from the liver. ANOVA and Pearson's correlation analyses were performed
      in R environment, and different clinicopathological subgroups were pairwise
      compared in Minitab. Gene expression matrices of cell lines and tissues were
      analyzed by Mantel's association test. RESULTS: Genewise hierarchical clustering
      revealed two subgroups with coordinate expression pattern in both the HCC cell
      lines and tissues: ROBO1, ROBO2, SLIT1 in one cluster, and ROBO4, SLIT2, SLIT3 in
      the other, respectively. Moreover, SLIT-ROBO expression predicted AFP-dependent
      subgrouping of HCC cell lines, but not that of liver tissues. ROBO1 and ROBO2
      were significantly up-regulated, whereas SLIT3 was significantly down-regulated
      in cell lines with high-AFP background. When compared to normal liver tissue,
      ROBO1 was found to be significantly overexpressed, while ROBO4 was down-regulated
      in HCC. We also observed that ROBO1 and SLIT2 differentiated histopathological
      subgroups of liver tissues depending on both tumor staging and differentiation
      status. However, ROBO4 could discriminate poorly differentiated HCC from other
      subgroups. CONCLUSION: The present study is the first in comprehensive and
      quantitative evaluation of SLIT-ROBO family gene expression in HCC, and suggests
      that the expression of SLIT-ROBO genes is regulated in hepatocarcinogenesis. Our
      results implicate that SLIT-ROBO transcription profile is bi-modular in nature,
      and that each module shows intrinsic variability. We also provide quantitative
      evidence for potential use of ROBO1, ROBO4 and SLIT2 for prediction of tumor
      stage and differentiation status.

PMID- 19114003
TI  - Primary health care delivery models in rural and remote Australia: a systematic
      review.
AB  - BACKGROUND: One third of all Australians live outside of its major cities. Access
      to health services and health outcomes are generally poorer in rural and remote
      areas relative to metropolitan areas. In order to improve access to services,
      many new programs and models of service delivery have been trialled since the
      first National Rural Health Strategy in 1994. Inadequate evaluation of these
      initiatives has resulted in failure to garner knowledge, which would facilitate
      the establishment of evidence-based service models, sustain and systematise them
      over time and facilitate transfer of successful programs. This is the first study
      to systematically review the available published literature describing innovative
      models of comprehensive primary health care (PHC) in rural and remote Australia
      since the development of the first National Rural Health Strategy (1993-2006).
      The study aimed to describe what health service models were reported to work,
      where they worked and why. METHODS: A reference group of experts in rural health
      assisted in the development and implementation of the study. Peer-reviewed
      publications were identified from the relevant electronic databases. 'Grey'
      literature was identified pragmatically from works known to the researchers,
      reference lists and from relevant websites. Data were extracted and synthesised
      from papers meeting inclusion criteria. RESULTS: A total of 5391 abstracts were
      reviewed. Data were extracted finally from 76 'rural' and 17 'remote' papers.
      Synthesis of extracted data resulted in a typology of models with five broad
      groupings: discrete services, integrated services, comprehensive PHC, outreach
      models and virtual outreach models. Different model types assume prominence with
      increasing remoteness and decreasing population density. Whilst different models
      suit different locations, a number of 'environmental enablers' and 'essential
      service requirements' are common across all model types. CONCLUSION: Synthesised
      data suggest that, moving away from Australian coastal population centres,
      sustainable models are able to address diseconomies of scale which result from
      large distances and small dispersed populations. Based on the service
      requirements and enablers derived from analysis of reported successful PHC
      service models, we have developed a conceptual framework that is particularly
      useful in underpinning the development of sustainable PHC models in rural and
      remote communities.

PMID- 19114004
TI  - Biomphalaria glabrata transcriptome: cDNA microarray profiling identifies
      resistant- and susceptible-specific gene expression in haemocytes from snail
      strains exposed to Schistosoma mansoni.
AB  - BACKGROUND: Biomphalaria glabrata is an intermediate snail host for Schistosoma
      mansoni, one of the important schistosomes infecting man. B. glabrata/S. mansoni
      provides a useful model system for investigating the intimate interactions
      between host and parasite. Examining differential gene expression between S.
      mansoni-exposed schistosome-resistant and susceptible snail lines will identify
      genes and pathways that may be involved in snail defences. RESULTS: We have
      developed a 2053 element cDNA microarray for B. glabrata containing clones from
      ORESTES (Open Reading frame ESTs) libraries, suppression subtractive
      hybridization (SSH) libraries and clones identified in previous expression
      studies. Snail haemocyte RNA, extracted from parasite-challenged resistant and
      susceptible snails, 2 to 24 h post-exposure to S. mansoni, was hybridized to the
      custom made cDNA microarray and 98 differentially expressed genes or gene
      clusters were identified, 94 resistant-associated and 4 susceptible-associated.
      Quantitative PCR analysis verified the cDNA microarray results for representative
      transcripts. Differentially expressed genes were annotated and clustered using
      gene ontology (GO) terminology and Kyoto Encyclopaedia of Genes and Genomes
      (KEGG) pathway analysis. 61% of the identified differentially expressed genes
      have no known function including the 4 susceptible strain-specific transcripts.
      Resistant strain-specific expression of genes implicated in innate immunity of
      invertebrates was identified, including hydrolytic enzymes such as cathepsin L, a
      cysteine proteinase involved in lysis of phagocytosed particles; metabolic
      enzymes such as ornithine decarboxylase, the rate-limiting enzyme in the
      production of polyamines, important in inflammation and infection processes, as
      well as scavenging damaging free radicals produced during production of reactive
      oxygen species; stress response genes such as HSP70; proteins involved in
      signalling, such as importin 7 and copine 1, cytoplasmic intermediate filament
      (IF) protein and transcription enzymes such as elongation factor 1alpha and EF-2.
      CONCLUSION: Production of the first cDNA microarray for profiling gene expression
      in B. glabrata provides a foundation for expanding our understanding of pathways
      and genes involved in the snail internal defence system (IDS). We demonstrate
      resistant strain-specific expression of genes potentially associated with the
      snail IDS, ranging from signalling and inflammation responses through to lysis of
      proteinacous products (encapsulated sporocysts or phagocytosed parasite
      components) and processing/degradation of these targeted products by
      ubiquitination.

PMID- 19114006
TI  - SR proteins and the nonsense-mediated decay mechanism are involved in human GLB1
      gene alternative splicing.
AB  - BACKGROUND: The human GLB1 gene is known to give rise to two alternatively
      spliced mRNAs, which encode two different proteins: lysosomal beta-galactosidase
      (beta-gal) and elastin-binding protein (EBP). The beta-gal transcript includes
      the 16 exons of the GLB1 gene. In the EBP transcript, exons 3, 4 and 6 are
      skipped, while exon 5 has a different reading frame. However, little is known on
      how this alternative splicing is regulated. FINDINGS: Cycloheximide treatment of
      HeLa cells and human fibroblasts revealed the presence of new transcripts that
      are otherwise degraded by nonsense-mediated decay (NMD). A minigene carrying the
      exons involved in the alternative splicing of GLB1 was constructed. Improving the
      acceptor-site scores of exons 3 or 4 increased the relative inclusion of these
      exons, but did not stop them being skipped in some transcripts. Overexpression of
      different SR proteins altered the relative proportion of the different
      transcripts produced by the minigene, indicating a possible mechanism for the
      regulation of the alternative splicing of GLB1. Finally, a comparison of this
      gene among different species was performed. CONCLUSION: In the processing of the
      GLB1 RNA several transcripts are generated, but only those with a correct reading
      frame are not degraded. The differential inclusion/exclusion of exons could be
      partially explained by the relatively weak splice sites in the exons involved.
      Different SR proteins have an effect on the process of skipping of these exons,
      at least in the minigene conditions, indicating a possible mechanism for the
      regulation of the alternative splicing of the GLB1 gene.

PMID- 19114005
TI  - Cilengitide induces cellular detachment and apoptosis in endothelial and glioma
      cells mediated by inhibition of FAK/src/AKT pathway.
AB  - BACKGROUND: The antiangiogenic agent cilengitide disrupts integrin binding to the
      extracellular matrix leading to apoptosis of activated endothelial cells.
      Integrins are also widely expressed in malignant glioma and integrin inhibitors
      may directly target tumor cells in this disease. Aim of the current study was to
      investigate effects of cilengitide on endothelial and glioma cells on molecular
      and cellular levels. RESULTS: Cilengitide caused dose-dependent detachment of
      endothelial cells from cell culture dishes. Proliferation of endothelial cells
      was significantly inhibited while the proportion of apoptotic cells was
      increased. Incubation of integrin-expressing glioma cells with cilengitide caused
      rounding and detachment after 24 hours as observed with endothelial cells.
      Cilengitide inhibited proliferation and induced apoptosis in glioma cells with
      methylated MGMT promotor when given alone or in combination with temozolomide. In
      endothelial as well as glioma cells cilengitide inhibited phosphorylation of FAK,
      Src and Akt. Assembly of cytoskeleton and tight junctions was heavily disturbed
      in both cell types. CONCLUSION: Cilengitide inhibits integrin-dependent
      signaling, causes disassembly of cytoskeleton, cellular detachment and induction
      of apoptosis in endothelial and glioma cells thereby explaining the profound
      activity of integrin inhibitors in gliomas. The combination of cilengitide with
      temozolomide exerted additive effects in glioma cells as observed clinically.

PMID- 19114007
TI  - Disability adjusted life years and minimal disease: application of a preference
      based relevance criterion to rank enteric pathogens.
AB  - BACKGROUND: Burden of disease estimates, which combine mortality and morbidity
      into a single measure, are used increasingly for priority setting in disease
      control, prevention and surveillance. However, because there is no clear
      exclusion criterion for highly prevalent minimal disease in burden of disease
      studies its application may be restricted. The aim of this study was to apply a
      newly developed relevance criterion based on preferences of a population panel,
      and to compare burden of disease estimates of five foodborne pathogens calculated
      with and without application of this criterion. METHODS: Preferences for twenty
      health states associated with foodborne disease were obtained from a population
      panel (n = 107) with the Visual Analogue Scale and the Time Trade-off (TTO)
      technique. The TTO preferences were used to derive the relevance criterion: if at
      least 50% of a panel of judges is willing to trade-off time in order to be
      restored to full health the health state is regarded as relevant, i.e. TTO median
      is greater than 0. Subsequently, the burden of disease of each of the five
      foodborne pathogens was calculated both with and without the relevance criterion.
      RESULTS: The panel ranked the health states consistently. Of the twenty health
      states, three did not meet the preference-based relevance criterion. Application
      of the relevance criterion reduced the burden of disease estimate of all five
      foodborne pathogens. The reduction was especially significant for norovirus and
      rotavirus, decreasing with 94% and 78% respectively. CONCLUSION: Individual
      preferences elicited with the TTO from a population panel can be used to
      empirically derive a relevance criterion for burden of disease estimates.
      Application of this preference-based relevance criterion results in considerable
      changes in ranking of foodborne pathogens.

PMID- 19114008
TI  - WGCNA: an R package for weighted correlation network analysis.
AB  - BACKGROUND: Correlation networks are increasingly being used in bioinformatics
      applications. For example, weighted gene co-expression network analysis is a
      systems biology method for describing the correlation patterns among genes across
      microarray samples. Weighted correlation network analysis (WGCNA) can be used for
      finding clusters (modules) of highly correlated genes, for summarizing such
      clusters using the module eigengene or an intramodular hub gene, for relating
      modules to one another and to external sample traits (using eigengene network
      methodology), and for calculating module membership measures. Correlation
      networks facilitate network based gene screening methods that can be used to
      identify candidate biomarkers or therapeutic targets. These methods have been
      successfully applied in various biological contexts, e.g. cancer, mouse genetics,
      yeast genetics, and analysis of brain imaging data. While parts of the
      correlation network methodology have been described in separate publications,
      there is a need to provide a user-friendly, comprehensive, and consistent
      software implementation and an accompanying tutorial. RESULTS: The WGCNA R
      software package is a comprehensive collection of R functions for performing
      various aspects of weighted correlation network analysis. The package includes
      functions for network construction, module detection, gene selection,
      calculations of topological properties, data simulation, visualization, and
      interfacing with external software. Along with the R package we also present R
      software tutorials. While the methods development was motivated by gene
      expression data, the underlying data mining approach can be applied to a variety
      of different settings. CONCLUSION: The WGCNA package provides R functions for
      weighted correlation network analysis, e.g. co-expression network analysis of
      gene expression data. The R package along with its source code and additional
      material are freely available at
      http://www.genetics.ucla.edu/labs/horvath/CoexpressionNetwork/Rpackages/WGCNA.

PMID- 19114009
TI  - MicroRNA profile changes in human immunodeficiency virus type 1 (HIV-1)
      seropositive individuals.
AB  - MicroRNAs (miRNAs) play diverse roles in regulating cellular and developmental
      functions. We have profiled the miRNA expression in peripheral blood mononuclear
      cells from 36 HIV-1 seropositive individuals and 12 normal controls. The HIV-1
      positive individuals were categorized operationally into four classes based on
      their CD4+ T-cell counts and their viral loads. We report that specific miRNA
      signatures can be observed for each of the four classes.

PMID- 19114010
TI  - Genomic selection of reference genes for real-time PCR in human myocardium.
AB  - BACKGROUND: Reliability of real-time PCR (RT-qPCR) data is dependent on the use
      of appropriate reference gene(s) for normalization. To date, no validated
      reference genes have been reported for normalizing gene expression in human
      myocardium. This study aimed to identify validated reference genes for use in
      gene expression studies of failed and non-failed human myocardium. METHODS:
      Bioinformatic analysis of published human heart gene expression arrays (195
      failed hearts, 16 donor hearts) was used to identify 10 stable and abundant genes
      for further testing. The expression stability of these genes was investigated in
      28 failed and 28 non-failed human myocardium samples by RT-qPCR using geNorm
      software. RESULTS: Signal recognition particle 14 kDa (SRP14), tumor protein,
      translationally-controlled 1 (TPT1) and eukaryotic elongation factor 1A1 (EEF1A1)
      were ranked the most stable genes. The commonly used reference gene,
      glyceraldehyde-3-phosphate dehydrogenase (GAPDH) was ranked the least stable of
      the genes tested. The normalization strategy was tested by comparing RT-qPCR data
      of both normalized and raw expression levels of brain natriuretic peptide
      precursor (NPPB), a gene known to be up-regulated in heart failure. Non
      normalized levels of NPPB exhibited a marginally significant difference between
      failed and non-failed samples (p = 0.058). In contrast, normalized NPPB
      expression levels were significantly higher in heart-failed patients compared
      with controls (p = 0.023). CONCLUSION: This study used publicly available gene
      array data to identify a strategy for normalization involving two reference genes
      in combination that may have broad application for accurate and reliable
      normalization of RT-qPCR data in failed and non-failed human myocardium.

PMID- 19114011
TI  - Two new splice variants in porcine PPARGC1A.
AB  - BACKGROUND: Peroxisome proliferator-activated receptor gamma coactivator 1alpha
      (PPARGC1A) is a coactivator with a vital and central role in fat and energy
      metabolism. It is considered to be a candidate gene for meat quality in pigs and
      is involved in the development of obesity and diabetes in humans. How its many
      functions are regulated, is however still largely unclear. Therefore a
      transcription profile of PPARGC1A in 32 tissues and 4 embryonic developmental
      stages in the pig was constructed by screening its cDNA for possible splice
      variants with exon-spanning primers. FINDINGS: This led to the discovery of 2 new
      splice variants in the pig, which were subsequently also detected in human
      tissues. In these variants, exon 8 was either completely or partly (the last 66
      bp were conserved) spliced out, potentially coding for a much shorter protein of
      respectively 337 and 359 amino acids (aa), of which the first 291 aa would be the
      same compared to the complete protein (796 aa). CONCLUSION: Considering the
      functional domains of the PPARGC1A protein, it is very likely these splice
      variants considerably affect the function of the protein and alternative splicing
      could be one of the mechanisms by which the diverse functions of PPARGC1A are
      regulated.

PMID- 19114012
TI  - The historical decline of tobacco smoking among Australian physicians: 1964-1997.
AB  - BACKGROUND: Physicians occupy an important position as tobacco control exemplars
      and their own smoking habits are known to influence how effective they may be in
      such a role. METHODS: A comprehensive review of all published manuscripts
      describing tobacco usage rates and tobacco control activities in the Australian
      medical profession between 1964 and 1997. RESULTS: Some of the earliest surveys
      revealed that around one-quarter of Australian physicians were smoking in the mid
      twentieth century, a rate which rapidly declined in the 1970s and 1980s, with
      reductions beyond that achieved by the general population. CONCLUSION: Overall,
      our review suggests that not only do contemporary Australian physicians smoke at
      very low rates when compared internationally, but that an active professional
      community can also make a real difference to the lifestyle choices of its own
      members.

PMID- 19114013
TI  - Fgf2 is expressed in human and murine embryonic choroid plexus and affects
      choroid plexus epithelial cell behaviour.
AB  - BACKGROUND: Although fibroblast growth factor (Fgf) signalling plays crucial
      roles in several developing and mature tissues, little information is currently
      available on expression of Fgf2 during early choroid plexus development and
      whether Fgf2 directly affects the behaviour of the choroid plexus epithelium
      (CPe). The purpose of this study was to investigate expression of Fgf2 in rodent
      and human developing CPe and possible function of Fgf2, using in vitro models.
      The application of Fgf2 to brain in vivo can affect the whole tissue, making it
      difficult to assess specific responses of the CPe. METHODS: Expression of Fgf2
      was studied by immunohistochemistry in rodent and human embryonic choroid plexus.
      Effects of Fgf2 on growth, secretion, aggregation and gene expression was
      investigated using rodent CPe vesicles, a three-dimensional polarized culture
      model that closely mimics CPe properties in vivo, and rodent CPe monolayer
      cultures. RESULTS: Fgf2 was present early in development of the choroid plexus
      both in mouse and human, suggesting the importance of this ligand in Fgf
      signalling in the developing choroid plexus. Parallel analysis of Fgf2 expression
      and cell proliferation during CP development suggests that Fgf2 is not involved
      in CPe proliferation in vivo. Consistent with this observation is the failure of
      Fgf2 to increase proliferation in the tri-dimensional vesicle culture model. The
      CPe however, can respond to Fgf2 treatment, as the diameter of CPe vesicles is
      significantly increased by treatment with this growth factor. We show that this
      is due to an increase in cell aggregation during vesicle formation rather than
      increased secretion into the vesicle lumen. Finally, Fgf2 regulates expression of
      the CPe-associated transcription factors, Foxj1 and E2f5, whereas transthyretin,
      a marker of secretory activity, is not affected by Fgf2 treatment. CONCLUSION:
      Fgf2 expression early in the development of both human and rodent choroid plexus,
      and its ability to modulate behaviour and gene expression in CPe, supports the
      view that Fgf signalling plays a role in the maintenance of integrity and
      function of this specialized epithelium, and that this role is conserved between
      rodents and humans.

PMID- 19114014
TI  - Chronic, low-dose rotenone reproduces Lewy neurites found in early stages of
      Parkinson's disease, reduces mitochondrial movement and slowly kills
      differentiated SH-SY5Y neural cells.
AB  - BACKGROUND: Parkinson's disease, the most common adult neurodegenerative movement
      disorder, demonstrates a brain-wide pathology that begins pre-clinically with
      alpha-synuclein aggregates ("Lewy neurites") in processes of gut enteric and
      vagal motor neurons. Rostral progression into substantia nigra with death of
      dopamine neurons produces the motor impairment phenotype that yields a clinical
      diagnosis. The vast majority of Parkinson's disease occurs sporadically, and
      current models of sporadic Parkinson's disease (sPD) can utilize directly infused
      or systemic neurotoxins. RESULTS: We developed a differentiation protocol for
      human SH-SY5Y neuroblastoma that yielded non-dividing dopaminergic neural cells
      with long processes that we then exposed to 50 nM rotenone, a complex I inhibitor
      used in Parkinson's disease models. After 21 days of rotenone, ~60% of cells
      died. Their processes retracted and accumulated ASYN-(+) and UB-(+) aggregates
      that blocked organelle transport. Mitochondrial movement velocities were reduced
      by 8 days of rotenone and continued to decline over time. No cytoplasmic
      inclusions resembling Lewy bodies were observed. Gene microarray analyses showed
      that the majority of genes were under-expressed. qPCR analyses of 11 mtDNA
      encoded and 10 nDNA-encoded mitochondrial electron transport chain RNAs' relative
      expressions revealed small increases in mtDNA-encoded genes and lesser regulation
      of nDNA-encoded ETC genes. CONCLUSION: Subacute rotenone treatment of
      differentiated SH-SY5Y neuroblastoma cells causes process retraction and partial
      death over several weeks, slowed mitochondrial movement in processes and appears
      to reproduce the Lewy neuritic changes of early Parkinson's disease pathology but
      does not cause Lewy body inclusions. The overall pattern of transcriptional
      regulation is gene under-expression with minimal regulation of ETC genes in spite
      of rotenone's being a complex I toxin. This rotenone-SH-SY5Y model in a
      differentiated human neural cell mimics changes of early Parkinson's disease and
      may be useful for screening therapeutics for neuroprotection in that disease
      stage.

PMID- 19114015
TI  - Redo aortic valve replacement after partial upper sternotomy (hemisternotomy) in
      a patient with idiopathic thrombocytopenia: a case report.
AB  - BACKGROUND: We present a case of redo aortic valve replacement in a patient with
      thrombocytopenia. The initial operation was performed through limited access
      transverse sternotomy. This is the first report of this kind in the literature.
      CASE PRESENTATION: A 62 year old Caucasian male farmer with thrombocytopenia had
      uneventful redo aortic valve replacement when the first xenograft failed after 9
      years, the transverse upper hemisternotomy in the first operation appearing to
      facilitate the redo complete sternotomy. CONCLUSION: With this only case of redo
      aortic valve replacement in our practice of 90 hemisternotomies over 10 years we
      present for consideration the use of a tissue valve in a complex relatively young
      patient.

PMID- 19114016
TI  - Optic nerve sheath meningioma: a case report.
AB  - A case of a 75-year old male with right-sided exopthalmos is presented. Outside
      proptosis of the right eye was initially observed 6 years ago. Opthalmological
      and endocrinological clinical examination as well as laboratory tests revealed no
      pathology from optic nerve disc, optic bulb and thyroid related hormones. MRI
      study demonstrated an optic nerve meningioma. The key imaging findings and the
      differential diagnosis were discussed in this present paper.

PMID- 19114017
TI  - Interventional cardiovascular magnetic resonance: still tantalizing.
AB  - The often touted advantages of MR guidance remain largely unrealized for
      cardiovascular interventional procedures in patients. Many procedures have been
      simulated in animal models. We argue these opportunities for clinical
      interventional MR will be met in the near future. This paper reviews technical
      and clinical considerations and offers advice on how to implement a clinical
      grade interventional cardiovascular MR (iCMR) laboratory. We caution that this
      reflects our personal view of the "state of the art."

PMID- 19114019
TI  - The effect of time-to-surgery on outcome in elderly patients with proximal
      femoral fractures.
AB  - BACKGROUND: Whether reducing time-to-surgery for elderly patients suffering from
      hip fracture results in better outcomes remains subject to controversial debates.
      METHODS: As part of a prospective observational study conducted between January
      2002 and September 2003 on hip-fracture patients from 268 acute-care hospitals
      all over Germany, we investigated the relationship of time-to-surgery with
      frequency of post-operative complications and one-year mortality in elderly
      patients (age > or =65) with isolated proximal femoral fracture (femoral neck
      fracture or pertrochanteric femoral fracture). Patients with short (< or =12 h),
      medium (> 12 h to < or =36 h) and long (> 36 h) times-to-surgery, counting from
      the time of the fracture event, were compared for patient characteristics,
      operative procedures, post-operative complications and one-year mortality.
      RESULTS: Hospital data were available for 2916 hip-fracture patients (mean age
      (SD) in years: 82.1 (7.4), median age: 82; 79.7% women). Comparison of groups
      with short (n = 802), medium (n = 1191) and long (n = 923) time-to-surgery
      revealed statistically significant differences in a few patient characteristics
      (age, American Society of Anesthesiologists ratings classification and type of
      admission) and in operative procedures (total hip endoprosthesis, hemi
      endoprosthetic implants, other osteosynthetic procedures). However, comparison of
      these same groups for frequency of postoperative complications revealed only some
      non-significant associations with certain complications such as post-operative
      bleeding requiring treatment (early surgery patients) and urinary tract
      infections (delayed surgery patients). Both unadjusted rates of one-year all
      cause mortality (between 18.1% and 20.5%), and the multivariate-adjusted hazard
      ratios (HR for time-to-surgery: 1.04; p = 0.55) showed no association between
      mortality and time-to-surgery. CONCLUSION: Although this study found a trend
      toward more frequent post-operative complications in the longest time-to-surgery
      group, there was no effect of time-to-surgery on mortality. Shorter time-to
      surgery may be associated with somewhat lower rates of post-operative
      complications such as decubitus ulcers, urinary tract infections, thromboses,
      pneumonia and cardiovascular events, and with somewhat higher rates of others
      such as post-operative bleeding or implant complications.

PMID- 19114018
TI  - Posttranslational regulation of Fas ligand function.
AB  - The TNF superfamily member Fas ligand acts as a prototypic death factor. Due to
      its ability to induce apoptosis in Fas (APO-1, CD95) expressing cells, Fas ligand
      participates in essential effector functions of the immune system. It is involved
      in natural killer cell- and T cell-mediated cytotoxicity, the establishment of
      immune privilege, and in termination of immune responses by induction of
      activation-induced cell death. In addition, Fas ligand-positive tumours may evade
      immune surveillance by killing Fas-positive tumour-infiltrating cells. Given
      these strong cytotoxic capabilities of Fas ligand, it is obvious that its
      function has to be strictly regulated to avoid uncontrolled damage. In
      hematopoietic cells, the death factor is stored in secretory lysosomes and is
      mobilised to the immunological synapse only upon activation. The selective
      sorting to and the release from this specific lysosomal compartment requires
      interactions of the Fas ligand cytosolic moiety, which mediates binding to
      various adapter proteins involved in trafficking and cytoskeletal reorganisation.
      In addition, Fas ligand surface expression is further regulated by
      posttranslational ectodomain shedding and subsequent regulated intramembrane
      proteolysis, releasing a soluble ectodomain cytokine into the extracellular space
      and an N-terminal fragment with a potential role in intracellular signalling
      processes. Moreover, other posttranslational modifications of the cytosolic
      domain, including phosphorylation and ubiquitylation, have been described to
      affect various aspects of Fas ligand biology. Since FasL is regarded as a
      potential target for immunotherapy, the further characterisation of its
      biological regulation and function will be of great importance for the
      development and evaluation of future therapeutic strategies.

PMID- 19114021
TI  - A rare tumoral combination, synchronous lung adenocarcinoma and mantle cell
      lymphoma of the pleura.
AB  - BACKGROUND: Coexistence of adenocarcinoma and mantle cell lymphoma in the same or
      different anatomical sites is extremely rare. We present a case of incidental
      discovery of primary lung adenocarcinoma and mantle cell lymphoma involving the
      pleura, during an axillary thoracotomy performed for a benign condition. CASE
      PRESENTATION: A 73-year old male underwent bullectomy and apical pleurectomy for
      persistent pneumothorax. A bulla of the lung apex was resected en bloc with a
      scar-like lesion of the lung, which was located in proximity with the bulla
      origin, by a wide wedge resection. Histologic examination of the stripped-off
      parietal pleura and of the bullectomy specimen revealed the synchronous
      occurrence of two distinct neoplasms, a lymphoma infiltrating the pleura and a
      primary, early lung adenocarcinoma. Immunohistochemical and fluorescence in situ
      hybridization assays were performed. The morphologic, immunophenotypic and
      genetic findings supported the diagnosis of primary lung adenocarcinoma
      (papillary subtype) coexisting with a non-Hodgkin, B-cell lineage, mantle cell
      lymphoma involving both, visceral and parietal pleura and without mediastinal
      lymph node involvement. The neoplastic lymphoid cells showed the characteristic
      immunophenotype of mantle cell lymphoma and the translocation t(11;14). The
      patient received 6 cycles of chemotherapy, while pulmonary function tests
      precluded further pulmonary parenchyma resection (lobectomy) for his
      adenocarcinoma. The patient is alive and without clinical and radiological
      findings of local recurrence or distant relapse from both tumors 14 months later.
      CONCLUSION: This is the first reported case of a rare tumoral combination
      involving simultaneously lung and pleura, emphasizing at the incidental discovery
      of the two coexisting neoplasms during a procedure performed for a benign
      condition. Any tissue specimen resected during operations performed for non
      tumoral conditions should be routinely sent for pathologic examination.

PMID- 19114020
TI  - DNA-microarrays identification of Streptococcus mutans genes associated with
      biofilm thickness.
AB  - BACKGROUND: A biofilm is a complex community of microorganisms that develop on
      surfaces in diverse environments. The thickness of the biofilm plays a crucial
      role in the physiology of the immobilized bacteria. The most cariogenic bacteria,
      mutans streptococci, are common inhabitants of a dental biofilm community. In
      this study, DNA-microarray analysis was used to identify differentially expressed
      genes associated with the thickness of S. mutans biofilms. RESULTS: Comparative
      transcriptome analyses indicated that expression of 29 genes was differentially
      altered in 400- vs. 100-microns depth and 39 genes in 200- vs. 100-microns
      biofilms. Only 10 S. mutans genes showed differential expression in both 400- vs.
      100-microns and 200- vs. 100-microns biofilms. All of these genes were
      upregulated. As sucrose is a predominant factor in oral biofilm development, its
      influence was evaluated on selected genes expression in the various depths of
      biofilms. The presence of sucrose did not noticeably change the regulation of
      these genes in 400- vs. 100-microns and/or 200- vs. 100-microns biofilms tested
      by real-time RT-PCR. Furthermore, we analyzed the expression profile of selected
      biofilm thickness associated genes in the luxS- mutant strain. The expression of
      those genes was not radically changed in the mutant strain compared to wild-type
      bacteria in planktonic condition. Only slight downregulation was recorded in
      SMU.2146c, SMU.574, SMU.609, and SMU.987 genes expression in luxS- bacteria in
      biofilm vs. planktonic environments. CONCLUSION: These findings reveal genes
      associated with the thickness of biofilms of S. mutans. Expression of these genes
      is apparently not regulated directly by luxS and is not necessarily influenced by
      the presence of sucrose in the growth media.

PMID- 19114022
TI  - Magnetic resonance imaging of the erector spinae muscles in Duchenne muscular
      dystrophy: implication for scoliotic deformities.
AB  - BACKGROUND: In Duchenne muscular dystrophy (DMD), the muscular degeneration often
      leads to the development of scoliosis. Our objective was to investigate how
      anatomical changes in back muscles can lead to scoliosis. Muscular volume and the
      level of fat infiltration in those muscles were thus evaluated, in non-scoliotic,
      pre-scoliotic and scoliotic patients. The overlying skin thickness over the apex
      level of scoliotic deformations was also measured to facilitate the
      interpretation of electromyographic signals when recorded on the skin surface.
      METHODS: In 8 DMD patients and two healthy controls with no known muscular
      deficiencies, magnetic resonance imaging (MRI) was used to measure continuously
      at 3 mm intervals the distribution of the erector spinae (ES) muscle in the T8-L4
      region as well as fat infiltration in the muscle and overlying skin thickness:
      four patients were non-scoliotic (NS), two were pre-scoliotic (PS, Cobb angle <
      15 degrees ) and two were scoliotic (S, Cobb angle >/= 15 degrees ). For each
      subject, 63 images 3 mm thick of the ES muscle were obtained in the T8-L4 region
      on both sides of the spine. The pixel dimension was 0.39 x 0.39 mm. With a
      commercial software, on each 12 bits image, the ES contour on the left and on the
      right sides of the spine were manually determined as well as those of its
      constituents i.e., the iliocostalis (IL), the longissimus (LO) and the spinalis
      (SP) muscles. Following this segmentation, the surfaces within the contours were
      determined, the muscles volume were obtained, the amount of fat infiltration
      inside each muscle was evaluated and the overlying skin thickness measured.
      FINDINGS: The volume of the ES muscle of our S and PS patients was found smaller
      on the convex side relative to the concave one by 5.3 +/- 0.7% and 2.8 +/- 0.2%
      respectively. For the 4 NS patients, the volume difference of this muscle between
      right and left sides was 2.1 +/- 1.5% and for the 2 controls, it was 1.4 +/-
      1.2%. Fat infiltration for the S and the PS patients was larger on the convex
      side than on the concave one (4.4 +/- 1.6% and 4.5 +/- 0.7% respectively) and the
      difference was more important near the apex. Infiltration was more important in
      the lateral IL muscle than in the medial SP and it was always larger near L2 than
      at any other spinal level. Fat infiltration was much more important in the ES for
      the DMD patients (49.9% +/- 1.6%) than for the two controls (2.6 +/- 0.8%). As
      for the overlying skin thickness measured near the deformity of the patients, it
      was larger on the concave than on the convex side: 14.8 +/- 6.1 vs 13.5 +/- 5.7
      mm for the S and 10.3 +/- 6.3 vs 9.8 +/- 5.6 mm for the PS. INTERPRETATION: In
      DMD patients, our results indicate that a larger replacement of muscles fibers by
      fat infiltration on one side of the spine is a factor that can lead to the
      development of scoliosis. Efforts to slow such an infiltration on the most
      affected side of the spine could thus be beneficial to those patients by delaying
      the apparition of the scoliotic deformation. In addition to anatomical
      considerations, results obtained from the same patients but in experiments
      dealing with electromyography recordings, point to differences in the muscular
      contraction mechanisms and/or of the neural input to back muscles. This is
      similar to the adolescent idiopathic scoliosis (AIS) where a role of the nervous
      system in the development of the deformation has also been suggested.

PMID- 19114023
TI  - Potential for La Crosse virus segment reassortment in nature.
AB  - The evolutionary success of La Crosse virus (LACV, family Bunyaviridae) is due to
      its ability to adapt to changing conditions through intramolecular genetic
      changes and segment reassortment. Vertical transmission of LACV in mosquitoes
      increases the potential for segment reassortment. Studies were conducted to
      determine if segment reassortment was occurring in naturally infected Aedes
      triseriatus from Wisconsin and Minnesota in 2000, 2004, 2006 and 2007. Mosquito
      eggs were collected from various sites in Wisconsin and Minnesota. They were
      reared in the laboratory and adults were tested for LACV antigen by
      immunofluorescence assay. RNA was isolated from the abdomen of infected
      mosquitoes and portions of the small (S), medium (M) and large (L) viral genome
      segments were amplified by RT-PCR and sequenced. Overall, the viral sequences
      from 40 infected mosquitoes and 5 virus isolates were analyzed. Phylogenetic and
      linkage disequilibrium analyses revealed that approximately 25% of infected
      mosquitoes and viruses contained reassorted genome segments, suggesting that LACV
      segment reassortment is frequent in nature.

PMID- 19114024
TI  - The oncogenic activity of the Src family kinase Hck requires the cooperative
      action of the plasma membrane- and lysosome-associated isoforms.
AB  - Hck is a phagocyte specific proto-oncogene of the Src family expressed as two
      isoforms, p59Hck and p61Hck. It plays a critical role in Bcr/Abl-chronic myeloid
      leukaemia and is able to transform fibroblasts in vitro. However, the
      tumourigenic activity of Hck and the respective oncogenic functions of Hck
      isoforms have not been examined. Tet-Off fibroblasts expressing constitutively
      active mutants of p59Hck and p61Hck together or individually were used. In
      contrast to cells expressing p59Hck(ca) or p61Hck(ca) alone, cells expressing
      both isoforms were transformed in vitro and induced tumour formation in 90% of
      nude mice within 2 weeks. This is the first demonstration of (i) the tumourigenic
      activity of Hck in mice, (ii) the cooperative action of the two Hck isoforms in
      vitro and in vivo. To our knowledge, this is the first example of a transforming
      activity 'split' in two requisite isoforms.

PMID- 19114025
TI  - Impact of pre-seasonal focal treatment on population densities of the mosquito
      Aedes aegypti in Trinidad, West Indies: a preliminary study.
AB  - A new pre-seasonal focal treatment strategy against Aedes aegypti L. (Diptera:
      Culicidae) mosquitoes is described for the first time. It was evaluated for 25
      weeks using ovitraps, and larval and pupal surveys in the townships of Curepe
      (treated) and St. Joseph (untreated), Trinidad, West Indies. Both townships were
      similar with respect to number of houses, size of human populations, the number
      of Ae. aegypti infested houses and containers. In March 2003, a total of 9403
      containers were inspected, of which 1.4% in Curepe (63/4499) and 1.3% in St.
      Joseph (64/4904) were positive for Ae. aegypti immature stages. Curepe had a
      lower percentage (12.7%) of the main type of breeding container present (small
      miscellaneous containers) than St. Joseph (28.1%). Following focal treatment
      during the month of April (2-3 weeks before the onset of the rainy season), the
      Ae. aegypti population declined significantly (P>0.01) from a Breteau index (BI;
      proportion of containers positive for larvae and pupae) of 19.0 to a minimum of
      6.0 and a pupae/person index (PI) of 1.23 to a minimum of 0.35 in May, while in
      the untreated town of St. Joseph, the BI steadily increased from 23 to 38 and the
      PI rose from 0.96 to 2.00 in August. Similar declines in other measures of
      population density (the number of positive houses and number of eggs collected in
      ovitraps) were observed in Curepe, while St. Joseph maintained PI of >1.50 and BI
      of >28. Furthermore, the Curepe Ae. aegypti population did not return to pre
      treatment levels until 9-11 weeks after treatment, far beyond the 6 weeks
      normally expected during vector suppression campaigns. The results suggest that
      timely application of pre-seasonal focal treatment with temephos together with
      standard control measures, such as source reduction of the most productive
      containers, can reduce the Breteau index to <5 and the pupae/person index to
      <0.71 (i.e., below the suggested dengue transmission thresholds for Trinidad),
      and extend the duration of vector suppression.

PMID- 19114026
TI  - Social isolation stimulates hippocampal estradiol synthesis.
AB  - 17beta-estradiol is synthesized de novo in the rat hippocampus. However, the
      regulatory mechanism of hippocampal estradiol synthesis has remained unclear. We
      investigated the effects of social isolation on rat hippocampal estradiol
      synthesis. Rats were divided into two groups: social isolation and pair housed
      group. Socially isolated rats were housed individually while pair housed rats
      were housed two per cage for 8 weeks. Social isolation activated the
      transcription of neurosteroidogenic molecules, including steroidogenic acute
      regulatory protein (StAR) and CYP19 (cytochrome P450arom). These two molecules
      are involved in the regulatory step for steroidogenesis and final step of
      estradiol synthesis. In contrast, the mRNA levels were not affected in rat
      olfactory bulb. The hippocampal estradiol content was increased in accordance
      with the increased mRNA levels. The hippocampal estradiol content exhibited
      correlations with the StAR and P450arom mRNA levels. These data suggest that
      social isolation may enhance de novo estradiol synthesis in the hippocampus.

PMID- 19114027
TI  - Halofuginone prevents extracellular matrix deposition in diabetic nephropathy.
AB  - Transforming growth factor-beta (TGF-beta) is known to promote the accumulation
      of extracellular matrix (ECM) and the development of diabetic nephropathy.
      Halofuginone, an analog of febrifugine, has been shown to block TGF-beta(1)
      signaling and subsequent type I collagen production. Here, the inhibitory effect
      of halofuginone on diabetic nephropathy was examined. Halofuginone suppressed
      Smad2 phosphorylation induced by TGF-beta(1) in cultured mesangial cells. In
      addition, the expression of TGF-beta type 2 receptor decreased by halofuginone.
      Halofuginone showed an inhibitory effect on type I collagen and fibronectin
      expression promoted by TGF-beta(1). An in vivo experiment using db/db mice
      confirmed the ability of halofuginone to suppress mesangial expansion and
      fibronectin overexpression in the kidneys. Moreover, an analysis of urinary 8
      OHdG level and dihydroethidium fluorescence revealed that halofuginone reduced
      oxidative stress in the glomerulus of db/db mice. These data indicate that
      halofuginone prevents ECM deposition and decreases oxidative stress, thereby
      suppressing the progression of diabetic nephropathy.

PMID- 19114028
TI  - Early lethality of beta-1,4-galactosyltransferase V-mutant mice by growth
      retardation.
AB  - The beta-1,4-galactosyltransferase (beta-1,4-GalT) V whose human and mouse genes
      were cloned by us has been suggested to be involved in the biosynthesis of N
      glycans and O-glycans, and lactosylceramide. To determine its biological
      function, beta-1,4-GalT V (B4galt5) mutant mice obtained by a gene trap method
      were analyzed. Analysis of pre- and post-implantation embryos revealed that the
      B4galt5(-/-) mice die by E10.5 while B4galt5(+/-) mice were born and grown
      normally. Histological study showed that most tissues are formed in B4galt5(-/-)
      embryos but their appearance at E10.5 is close to that of B4galt5(+/-) embryos at
      E9.0-9.5. The results indicate that the growth is delayed by one to one and half
      day in B4galt5(-/-) embryos when compared to B4galt5(+/-) embryos, which results
      in early death of the embryos by E10.5, probably due to hematopoietic and/or
      placental defects.

PMID- 19114029
TI  - Investigating the role of class-IA PI 3-kinase isoforms in adipocyte
      differentiation.
AB  - PI 3-kinases, in particular class-IA, are key signalling molecules controlling
      many cellular processes including growth, proliferation, migration and
      differentiation. In this study, we have used a collection of isoform selective PI
      3-kinase inhibitors to determine whether attenuation of signalling through class
      IA PI 3-kinase isoforms will impact adipocyte differentiation. First, we analysed
      the expression profiles and found that fibroblastic pre-adipocytes express
      detectable levels of p110alpha and p110delta and that after differentiation,
      p110delta levels fall while p110alpha levels rise, together with C/EBPalpha and
      PPARgamma. When using specific inhibitors during the differentiation process, we
      observed that neither p110beta nor p110delta inhibition, had any significant
      effect. In contrast PIK-75, a selective p110alpha inhibitor completely abolished
      adipocyte differentiation as assessed by morphology, transcript and protein
      levels of adipocyte markers. These results indicate that long term treatment with
      p110alpha inhibitors could potentially have a severe impact on fat cell numbers
      in vivo.

PMID- 19114030
TI  - Targeting nanodisks via a single chain variable antibody--apolipoprotein chimera.
AB  - Nanodisks (ND) are nanometer scale complexes of phospholipid and apolipoprotein
      that have been shown to function as drug delivery vehicles. ND harboring
      significant quantities of the antifungal agent, amphotericin B, or the bioactive
      isoprenoid, all trans retinoic acid, have been generated and characterized. As
      currently formulated, ND possess limited targeting capability. In this study, we
      constructed a single chain variable antibody (scFv).apolipoprotein chimera and
      assessed the ability of this fusion protein to form ND and recognize the antigen
      to which the scFv is directed. Data obtained revealed that alpha-vimentin
      scFv.apolipoprotein A-I is functional in ND formation and antigen recognition,
      opening the door to the use of such chimeras in targeting drug-enriched ND to
      specific tissues.

PMID- 19114031
TI  - Calcineurin regulates phosphorylation status of transcription factor osterix.
AB  - Osterix is an osteoblast-specific transcriptional factor that is essential for
      osteoblast differentiation and bone formation. Calcineurin regulates bone
      formation through modulating osteoblast differentiation. However, post
      translational modification of osterix such as phosphorylation and interactions
      between osterix and calcineurin remains unclear. In the present study, we
      demonstrated that calcineurin interacted with osterix determined by
      immunoprecipitation assay and Western analysis. Immunocytochemical study also
      revealed that osterix and calcineurin were co-localized in nucleus. Deletion of
      calcineurin binding motif on osterix molecule disrupted osterix-calcineurin
      interaction. Phosphorylation status of osterix was augmented by treatment with
      phosphatase inhibitors, FK506 and calyculin A. In contrast, treatment of
      recombinant calcineurin reduced phosphorylation status of osterix. Our present
      study suggests that calcineurin has an important role in the function of osterix
      through its modification of phosphorylation.

PMID- 19114033
TI  - ATF4 is necessary and sufficient for ER stress-induced upregulation of REDD1
      expression.
AB  - In response to a variety of cell stresses, e.g. endoplasmic reticulum (ER)
      stress, expression of REDD1 (regulated in development and DNA damage responses)
      is transcriptionally upregulated. However, the mechanism through which ER stress
      acts to upregulate REDD1 expression is unknown. In the present study, REDD1
      expression was found to be upregulated by ER stress in several cell lines.
      However, in MEF cells lacking the eIF2alpha kinase PERK, ER stress failed to
      upregulate REDD1 expression, demonstrating that phosphorylation of eIF2alpha was
      necessary for the effect. Moreover, ER stress led to upregulated expression of
      the transcription factor ATF4, but in MEF cells lacking ATF4, REDD1 mRNA
      expression was not increased by ER stress. In contrast, exogenous expression of
      ATF4 was sufficient to induce REDD1 expression. Overall, the results suggest that
      REDD1 expression is upregulated during ER stress through a mechanism involving
      activation of PERK, phosphorylation of eIF2alpha, and increased ATF4 expression.

PMID- 19114032
TI  - PPAR-gamma agonist protects against intestinal injury during necrotizing
      enterocolitis.
AB  - Necrotizing enterocolitis (NEC) remains a lethal condition for many premature
      infants. Peroxisome proliferator-activated receptor-gamma (PPAR-gamma), a member
      of the nuclear hormone receptor family, has been shown to play a protective role
      in cellular inflammatory responses; however, its role in NEC is not clearly
      defined. We sought to examine the expression of PPAR-gamma in the intestine using
      an ischemia-reperfusion (I/R) model of NEC, and to assess whether PPAR-gamma
      agonist treatment would ameliorate I/R-induced gut injury. Swiss-Webster mice
      were randomized to receive sham (control) or I/R injury to the gut induced by
      transient occlusion of superior mesenteric artery for 45 min with variable
      periods of reperfusion. I/R injury resulted in early induction of PPAR-gamma
      expression and activation of NF-kappaB in small intestine. Pretreatment with PPAR
      gamma agonist, 15d-PGJ(2), attenuated intestinal NF-kappaB response and I/R
      induced gut injury. Activation of PPAR-gamma demonstrated a protective effect on
      small bowel during I/R-induced gut injury.

PMID- 19114034
TI  - PTEN downregulates p75NTR expression by decreasing DNA-binding activity of Sp1.
AB  - p75NTR is expressed throughout the nervous system and its dysregulation is
      associated with pathological conditions. We have recently demonstrated a
      signalling cascade initiated by laminin (LN), which upregulates PTEN and
      downregulates p75NTR. Here we investigate the mechanism by which PTEN modulates
      p75NTR. Studies using PTEN mutants show that its protein phosphatase activity
      directly modulates p75NTR protein expression. Nuclear relocalization of PTEN
      subsequent to LN stimulation suggests transcriptional control of p75NTR
      expression, which was confirmed following EMSA and ChIP analysis of Sp1
      transcription factor binding activity. LN and PTEN independently decrease the DNA
      binding ability of PTEN to the p75NTR promoter. Sp1 regulation of p75NTR occurs
      via dephosphorylation of Sp1, thus reducing p75NTR transcription and protein
      expression. This mechanism represents a novel regulatory pathway which controls
      the expression level of a receptor with broad implications not only for the
      development of the nervous system but also for progression of pathological
      conditions.

PMID- 19114035
TI  - Emerging functions of ribosomal proteins in gene-specific transcription and
      translation.
AB  - Ribosomal proteins have remained highly conserved during evolution presumably
      reflecting often critical functions in ribosome biogenesis or mature ribosome
      function. In addition, several ribosomal proteins possess distinct extra
      ribosomal functions in apoptosis, DNA repair and transcription. An increasing
      number of ribosomal proteins have been shown to modulate the trans-activation
      function of important regulatory proteins such as NF-kappaB, p53, c-Myc and
      nuclear receptors. Furthermore, a subset of ribosomal proteins can bind directly
      to untranslated regions of mRNA resulting in transcript-specific translational
      control outside of the ribosome itself. Collectively, these findings suggest that
      ribosomal proteins may have a wider functional repertoire within the cell than
      previously thought. The future challenge is to identify and validate these novel
      functions in the background of an often essential primary function in ribosome
      biogenesis and cell growth.

PMID- 19114036
TI  - Influence of cryoprotectants on abnormality and motility of baung (Mystus
      nemurus) spermatozoa after long-term cryopreservation.
AB  - Study on the effect of cryoprotectants on abnormality and motility of baung,
      Mystus nemurus spermatozoa were evaluated using transmission and scanning
      electron microscopy. Four cryoprotectants, dmso, ethanol, methanol and glycerol
      at concentration of 10% were tested in triplicates. Three ml of fresh sperm which
      was diluted with 60 ml of ringer solution was added to each of twelve 5-ml vials
      containing of 0.50-ml of the cryoprotectants. The vials were placed in an icebox
      containing dry ice 5 min and then storage into container containing liquid
      nitrogen for 13 months. The effect of cryoprotectants on the spermatozoa
      abnormality and motility were significant (P<0.05). The spermatozoa abnormality
      was significantly lower in methanol (62.65%) compared with the other
      cryoprotectants. The spermatozoa motility was higher in methanol, but not
      significantly different with ethanol (P>0.05). It is a negative correlation
      between sperm motility and abnormality. Generally, higher abnormalities of
      spermatozoa resulted low motility.

PMID- 19114037
TI  - Structural changes of the trabecular meshwork in different kinds of glaucoma.
AB  - The morphology of the trabecular meshwork in three types of open angle glaucoma:
      primary open angle glaucoma (POAG), corticosteroid-induced glaucoma and
      pigmentary glaucoma (PG) are described. Ageing is one major risk factor for
      development of POAG. It is assumed that preexisting age-related changes of the
      trabecular meshwork (TM) play a role for the development of increased outflow
      resistance and intraocular pressure (IOP) in various types of glaucoma. These age
      related changes in the TM develop concomitant with that of presbyopia. Therefore
      the functional relationship between ciliary muscle (CM) and TM and the age
      related changes in morphology of the outflow system are described first. One main
      finding in the ageing TM concerns changes of the elastic fiber network and the
      anterior elastic tendons of the CM. There is an increase in thickness of the
      sheath of the elastic fibers. Cross-sections through these fibers with their
      sheath appear as extracellular plaques and were therefore termed "sheath derived
      plaques" (SD-plaques). Morphologically, the TM changes in POAG resemble that of
      the ageing TM, but in POAG there is a significant increase in SD-plaques compared
      to age-matched controls. This increase is due to fine fibrils and other
      components of the extracellular matrix (ECM) that adhere to the sheaths of the
      elastic fibers and their connections to the inner wall endothelium. In POAG eyes
      there is also a marked loss of TM cells, at places leading to fusion and
      thickening of trabecular lamellae. In steroid-induced glaucoma there is also an
      increase in fine fibrillar material in the subendothelial region of SC. In
      contrast to POAG eyes these fibrils do not adhere to the sheath of the elastic
      fibers but are deposited underneath the inner wall endothelium. The main finding
      in steroid-induced glaucoma is an accumulation of basement membrane-like material
      staining for type IV collagen. These accumulations are found throughout all
      layers of the TM. In pigmentary glaucoma loss of cells was more prominent than in
      POAG eyes. Presumably, this cell loss occurs after overload of TM cells with
      pigment granules. Denuded TM lamellae fuse and the TM collapses. In the
      subendothelial region of these collapsed TM areas an increase in ECM presumably
      due to underperfusion was observed. At other places SC was occluded and the
      cribriform region appeared disorganized. In most parts of the circumference of
      the eye, the TM cells contained pigment granules. Occlusion of TM spaces by
      pigment granules or cells loaden with pigment was not seen in eyes with PG.

PMID- 19114038
TI  - Toxoplasma gondii: effect of maternal infection in the development of lymphoid
      organs of BALB/c neonates.
AB  - Toxoplasmosis is one of the worldwide parasitic zoonoses. Alterations in the
      lymphopoietic system are still poorly studied. We analyzed lymphoid organs of
      BALB/c mice neonates from Toxoplasma gondii-intraperitoneally-infected mothers on
      19th day of gestation, with 30 tachyzoites of strain RH. Normal non-infected
      pregnant females were used as controls. At 7 days after birth, animals were
      classified as neonates from infected (NIM) and neonates from non-infected mothers
      (NNIM). Weight of the thymus and number of thymic cells in NIM were decreased,
      percentage of apoptosis was significantly increased. Decrease in lymphocytes and
      monocytes and an increase of plasma cells were observed in bone marrow of NIM.
      Peripheral blood of NIM showed an increase of monocytes and neutrophils and a
      decrease in lymphocytes. Infection of the mother during the last day of gestation
      provokes in the neonates changes in the lymphoid organs that could explain
      survival of 75% of them.

PMID- 19114039
TI  - In vitro effects of growth factors and hormones on three Perkinsus species and
      increased proliferation of P. marinus during cloning.
AB  - Clonal cultures are essential for the genotypic and phenotypic characterization
      of Perkinsus species but their cloning, especially of P. marinus, can be tedious.
      The use of a growth factor and hormone supplement to facilitate cloning was,
      therefore, investigated. Many of the 16 supplements tested significantly
      increased P. marinus and P. olseni proliferation but only two significantly
      increased P. chesapeaki proliferation. The concentration of the most effective
      supplement for all three Perkinsus species (i.e., endothelial cell growth
      supplement, ECGS) and medium dilution were then optimized for P. marinus cultured
      at low densities. Finally, the advantage of using conditioned culture medium, a
      feeder layer, and ECGS alone and in different combinations to improve cloning of
      P. marinus were compared. Using conditioned culture medium, a feeder layer and
      ECGS in combination, each cell (N=7) seeded singly yielded clonal cultures with
      253+/-167 cells after 21 days. In contrast, only 4 out of 7 cells seeded singly
      in culture medium yielded clonal cultures with 5+/-4 cells after 21 days.

PMID- 19114040
TI  - Stress induces tRNA cleavage by angiogenin in mammalian cells.
AB  - tRNAs play a central role in protein translation, acting as the carrier of amino
      acids. By cloning microRNAs, we unexpectedly obtained some tRNA fragments
      generated by tRNA cleavage in the anticodon loop. These tRNA fragments are
      present in many cell lines and different mouse tissues. In addition, various
      stress conditions can induce this tRNA cleavage event in mammalian cells. More
      importantly, angiogenin (ANG), a member of RNase A superfamily, appears to be the
      nuclease which cleaves tRNAs into tRNA halves in vitro and in vivo. These results
      imply that angiogenin plays an important physiological role in cell stress
      response, except for the known function of inducing angiogenesis.

PMID- 19114041
TI  - Nitric oxide accumulation is required to protect against iron-mediated oxidative
      stress in frataxin-deficient Arabidopsis plants.
AB  - Frataxin is a mitochondrial protein that is conserved throughout evolution. In
      yeast and mammals, frataxin is essential for cellular iron (Fe) homeostasis and
      survival during oxidative stress. In plants, frataxin deficiency causes increased
      reactive oxygen species (ROS) production and high sensitivity to oxidative
      stress. In this work we show that a knock-down T-DNA frataxin-deficient mutant of
      Arabidopsis thaliana (atfh-1) contains increased total and organellar Fe levels.
      Frataxin deficiency leads also to nitric oxide (NO) accumulation in both, atfh-1
      roots and frataxin null mutant yeast. Abnormally high NO production might be part
      of the defence mechanism against Fe-mediated oxidative stress.

PMID- 19114042
TI  - Novel function of C5 protein as a metabolic stabilizer of M1 RNA.
AB  - Escherichia coli RNase P is a ribonucleoprotein composed of a large RNA subunit
      (M1 RNA) and a small protein subunit (C5 protein). We examined if C5 protein
      plays a role in maintaining metabolic stability of M1 RNA. The sequestration of
      C5 protein available for M1 RNA binding reduced M1 RNA stability in vivo, and its
      reduced stability was recovered via overexpression of C5 protein. In addition, M1
      RNA was rapidly degraded in a temperature-sensitive C5 protein mutant strain at
      non-permissive temperatures. Collectively, our results demonstrate that the C5
      protein metabolically stabilizes M1 RNA in the cell.

PMID- 19114043
TI  - The FHA-containing protein GarA acts as a phosphorylation-dependent molecular
      switch in mycobacterial signaling.
AB  - Fork-head associated (FHA) domains are widely found in bacteria, but their
      cellular functions remain unclear. Here, we focus on Mycobacterium tuberculosis
      GarA, an FHA-containing protein conserved in actinomycetes that is phosphorylated
      by different Ser/Thr protein kinases. Using various physicochemical approaches,
      we show that phosphorylation significantly stabilizes GarA, and that its FHA
      domain interacts strongly with the phosphorylated N-terminal extension.
      Altogether, our results indicate that phosphorylation triggers an intra-molecular
      protein closure, blocking the phosphothreonine-binding site and switching off the
      regulatory properties of GarA. The model can explain the reported functions of
      this mycobacterial protein as regulator of glycogen degradation and glutamate
      metabolism.

PMID- 19114044
TI  - Enzymatic characteristics of two novel Myxococcus xanthus enzymes, PdeA and PdeB,
      displaying 3',5'- and 2',3'-cAMP phosphodiesterase, and phosphatase activities.
AB  - Myxococcus xanthus PdeA and PdeB, enzymes homologous to class III 3',5'-cyclic
      nucleotide phosphodiesterases, hydrolyzed 3',5'- and 2',3'-cyclic AMP (cAMP) to
      adenosine, and also demonstrated phosphatase activity toward nucleoside 5'-tri-,
      5'-di-, 5'- and 3'-monophosphates with highest activities for nucleoside 5'
      monophosphates. The substrate specificities of PdeA and PdeB show no similarity
      to that of any known cNMP phosphodiesterase, nucleotidase, or phosphatase. The
      enzyme activities of PdeA and PdeB were stimulated by 50 microM Mn(2+) or Co(2+).
      The K(m) values of PdeA and PdeB for 3',5'-cAMP, 2',3'-cAMP, 5'-ATP, and 5'-AMP
      were in the low micromolar range (1.4-12.5 microM).

PMID- 19114045
TI  - Dopamine-melatonin neurons in the avian hypothalamus and their role as
      photoperiodic clocks.
AB  - A timing mechanism in the brain governs reproduction in seasonally breeding
      temperate zone birds by triggering gonad development in response to long days in
      the spring. The neural mechanism(s) responsible for the timing and induction of
      reproductive activity by this clock are unknown. Utilizing in situ hybridization,
      immunocytochemistry and reverse transcriptase-polymerase chain reaction
      techniques, a group of dopamine (DA) neurons in the premammillary nucleus (PMM)
      of the caudal turkey hypothalamus that synthesize and colocalize both DA and
      melatonin (MEL) were identified. In addition, these neurons are found to express
      clock genes and the circadian photoreceptor melanopsin. DA-MEL neurons reach
      threshold activation (c-fos expression) when a light pulse is given during the
      photosensitive phase. This is associated with increases in the number of
      gonadotropin releasing hormone-I (GnRH-I) neurones activated, as well as an up
      regulation of GnRH-I mRNA expression. The expression of tyrosine hydroxylase (TH;
      the rate limiting enzyme in DA biosynthesis) and tryptophan hydroxylase 1, (TPH1;
      the first enzyme in MEL biosynthesis) and consequently DAergic-MELergic
      activities are associated with the daily light-dark cycle. TPH1 mRNA expression
      shows low levels during the light phase and high levels during the dark phase of
      the light/dark illumination cycle and is 180 degrees out of phase with the rhythm
      of TH mRNA expression. Hypothalamic DA-MEL neurons may constitute a critical
      cellular process involved in the generation and expression of seasonal
      reproductive rhythms and suggests a previously undescribed mechanism(s) by which
      light signals gain access to neural targets.

PMID- 19114046
TI  - Gonadotrophin subunit and GnRH receptor gene expression in the pars distalis of
      the equine pituitary.
AB  - In the horse, pronounced changes in fertility occur annually in response to
      photoperiod. However, the mechanisms regulating gonadotrophin synthesis and
      release in this species remain unclear. Here, we investigated the expression of
      gonadotrophin subunits and GnRH receptor (GnRH-R) mRNA in the pituitary glands of
      Thoroughbred horses during the breeding (BS) and non-breeding (NBS) season.
      Seasonal effects on the prevalence of gonadotrophs in the pars distalis were also
      examined. GnRH-R and common alpha-, LHbeta- and FSHbeta-subunit mRNA contents
      were determined by Northern analysis and the prevalence of LH-gonadotrophs
      assessed by immunohistochemistry in pituitaries from sexually active females
      (mares) in the BS, and sexually inactive mares in the NBS. These variables were
      then measured in castrated male horses (geldings). In mares, pituitary content of
      FSHbeta mRNA was significantly higher in the NBS (P<0.01). Conversely, the
      content of common alpha-subunit mRNA was significantly higher during the BS
      (P<0.05). In contrast, GnRH-R and LHbeta mRNA abundance were unaffected by
      season. Interestingly, whereas no seasonal effects were apparent on the number of
      LH-gonadotrophs/field, the proportion of LH cells (in relation to all other
      cells) was higher in BS than NBS animals (P<0.05); this resulted from an
      increased number of non-gonadotroph cells during the NBS (P<0.05). In geldings,
      no significant seasonal effects were detected for any of the variables
      investigated (P>0.05). These results reveal robust seasonal effects on common
      alpha-subunit and FSHbeta gene expression in the pituitary of the mare, in the
      absence of detectable changes in the content of LHbeta or GnRH-R mRNA.

PMID- 19114047
TI  - Heterorhabditis sonorensis n. sp. (Nematoda: Heterorhabditidae), a natural
      pathogen of the seasonal cicada Diceroprocta ornea (Walker) (Homoptera:
      Cicadidae) in the Sonoran desert.
AB  - A new Heterorhabditis species was isolated from nymphal stages of the seasonal
      cicada Diceroprocta ornea (Walker) in an asparagus field in the state of Sonora,
      Mexico. Concomitantly, another isolate of the same nematode species was also
      collected from an oak woodland habitat in the Chiricahua mountain range in
      southeastern Arizona. Morphological and molecular studies together with cross
      hybridization tests indicate these two isolates are conspecific and represent a
      new undescribed Heterorhabditis sp. This new species is distinguished from other
      species in this genus by a combination of several qualitative and quantitative
      morphological traits. Key diagnostic features include: presence of a pronounced
      post-anal swelling in the hermaphrodite; male with nine pairs of bursal rays,
      with pairs 4 and 7 bent outwards and one pair of papillae placed on the cloacal
      opening, value of D% (average: 79); infective juveniles with a well developed
      cuticular tooth, long tail (average: 105mum) and values of D% (average: 90) and
      E% (average: 99). In addition to these diagnostic characters, cross-hybridization
      tests between the new species with H. bacteriophora and H. mexicana yielded no
      fertile progeny. Comparison of ITS rDNA sequences with other available sequences
      of described species depicted the two isolates as a new species. Phylogenetic
      analysis of these sequence data placed H. sonorensis n. sp. as a member of the
      indica-group.

PMID- 19114048
TI  - Clonal expansion of different mtDNA variants without selective advantage in solid
      tumors.
AB  - In search of tumor-specific mitochondrial DNA (mtDNA) mutations in head and neck
      squamous cell cancer, we found heteroplasmy in the blood of two individuals,
      i.e., these individuals carried two alleles of mtDNA. In both cases, the tumor
      was found to be homoplasmic, i.e., it contained only one of the two mtDNA alleles
      present in blood. More interestingly, in one case the tumor had acquired the wild
      type allele, while in the other case it contained the mutant allele only.
      Sequencing of the whole 16.5 kb mtDNA showed that the observed heteroplasmic
      positions in the D-loop region, nucleotides 152 and 16187, respectively, were the
      only differences between tumor and blood mtDNA genotypes in these individuals.
      Our findings thus strongly support the hypothesis that accumulation of mtDNA
      mutations in solid tumors occurs by clonal and random expansion of pre-existing
      alleles and is not necessary for the metabolic changes generally associated with
      tumor formation, the Warburg effect.

PMID- 19114049
TI  - Urinary 8-oxodeoxyguanosine levels in children exposed to air pollutants.
AB  - Oxidative stress is believed to be one of the mechanisms of effects of air
      pollution to human health. We investigated levels of 8-oxodeoxyguanosine (8
      oxodG), a marker of oxidative damage to DNA, in urine samples of 894 children
      from two districts in the Czech Republic: Teplice and Prachatice. We assessed the
      association between 8-oxodG levels and exposure to particulate matter of
      different size: <or=10 microm (PM10), <or=2.5 microm (PM2.5) and carcinogenic
      polycyclic aromatic hydrocarbons (c-PAHs); as well as between 8-oxodG levels and
      individual lifestyle, health and pregnancy outcomes. An ELISA technique was used
      for analysis of 8-oxodG levels. Median levels (range) of 8-oxodG in children from
      Teplice vs. Prachatice were as follows: 14.6 (3.1-326.5) nmol/mmol vs. 15.2 (3.0
      180.8) nmol/mmol creatinine (p=0.34). Levels of 8-oxodG were elevated in children
      exposed to environmental tobacco smoke (ETS) (p<0.05) and among the Gypsy
      population (p<0.01). Levels of 8-oxodG decreased with the child's age (p<0.001)
      and increasing level of the mother's education (p<0.01). Multivariate statistical
      analyses confirmed the effect of the child's age and ETS exposure on 8-oxodG
      levels. The exposure to PM10 and PM2.5 measured by stationary monitors during a 7
      day period before urine collection, as well as the exposure to c-PAHs measured
      during 3-day periods 1-3 and 7-9 days before urine collection were identified as
      factors affecting 8-oxodG levels in multivariate models. The obtained results
      indicate that 8-oxodG is a sensitive biomarker for measuring the exposure of
      children to air pollution.

PMID- 19114050
TI  - Development and persistence of long-lasting behavioral sensitization to cocaine
      in female mice: role of the nNOS gene.
AB  - Our recent studies have shown that the neuronal nitric oxide synthase (nNOS) gene
      is required for the development and persistence of psychomotor sensitization to
      cocaine in adult but not adolescent male mice (Balda, M.A., Anderson, K.L.,
      Itzhak, Y., 2008. Differential role of the nNOS gene in the development of
      behavioral sensitization to cocaine in adolescent and adult B6;129S mice.
      Psychopharmacology (Berlin) 200, 509-519.). The aim of the present study was to
      investigate the contribution of the nNOS gene to cocaine-induced behavioral
      sensitization in adolescent and adult female mice. Adolescent and adult wild type
      (WT) and nNOS knockout (KO) mice received saline or cocaine (20 mg/kg) for 5 days
      and then were challenged with cocaine (20 mg/kg) after a drug-free period of
      either 10, 30, or 90 days. Context-dependent sensitization was determined by
      measuring saline-induced locomotor activity in the previously cocaine-paired
      environment. Results show that adolescent females of both genotypes, like their
      adult counterparts, developed long-lasting behavioral sensitization to cocaine (a
      three-month period), suggesting high vulnerability of females to cocaine
      regardless of age. An effect of genotype was observed in the initiation of
      sensitization, e.g., delayed onset in the absence of the nNOS gene. The only age
      dependent difference observed was that adult, but not adolescent mice developed
      context-dependent sensitization. The present study suggests that long-term
      expression of cocaine-induced behavioral sensitization in females (adolescent and
      adult) is nNOS-independent, unlike our previous findings in adult males.

PMID- 19114051
TI  - Choosing between alternative wrist postures: action planning needs perception.
AB  - When normal subjects grasp with their right hand a rectangular object placed at
      different orientations in the horizontal plane, they change from a 'thumb left'
      (clockwise) to a 'thumb right' (anti-clockwise) grasp when the orientation
      exceeds about 110 degrees , with respect to the mid-sagittal plane. This suggests
      planning of the final grip orientation at, or before the start of the prehension
      movement. The current study assessed performance of two visual agnosic patients
      (SB and DF) on a grasping task requiring the planning of final grip posture. Five
      healthy subjects were also tested. Subjects were required to grasp a triangular
      section block, which was presented at one of seven different orientations (80-140
      degrees). The healthy subjects showed a consistent relation between object
      orientation and hand orientation just before contact. In addition, they
      consistently used a clockwise grasp when object orientation was less than 100
      degrees , and an anti-clockwise grasp when it was more than 110 degrees, with a
      sharply defined switch-point being identifiable for each subject. For both visual
      agnosic patients, hand orientation was also reliably related to object
      orientation. However, the selection of grasp posture was markedly abnormal: they
      did not consistently switch between clockwise and anti-clockwise grasps within
      the normal orientation range, and the switch, when it did occur, was not at all
      sharply defined. These results suggest that the planning of hand orientation
      during a grasp depends on a perceptually based judgement of the awkwardness of
      alternative movements. This would presumably involve ventral stream processing,
      which is disrupted in the visual agnosic patients.

PMID- 19114052
TI  - Semantic memory is key to binding phonology: converging evidence from immediate
      serial recall in semantic dementia and healthy participants.
AB  - Patients with semantic dementia (SD) make numerous phoneme migration errors when
      recalling lists of words they no longer fully understand, suggesting that word
      meaning makes a critical contribution to phoneme binding in verbal short-term
      memory. Healthy individuals make errors that appear similar when recalling lists
      of nonwords, which also lack semantic support. Although previous studies have
      assumed that the errors in these two groups stem from the same underlying cause,
      they have never been directly compared. We tackled this issue by examining
      immediate serial recall for SD patients and controls on "pure" word lists and
      "mixed" lists that contained a mixture of words and nonwords. SD patients were
      equally poor at pure and mixed lists and made numerous phoneme migration errors
      in both conditions. In contrast, controls recalled pure lists better than mixed
      lists and only produced phoneme migrations for mixed lists. We also examined the
      claim that semantic activation is critical for words in the primacy portion of
      the list. In fact, the effect of mixed lists was greatest for later serial
      positions in the control group and in the SD group recall was poorest towards the
      ends of lists. These results suggest that mixing nonwords with words in healthy
      participants closely mimics the impact of semantic degradation in SD on word list
      recall. The study provides converging evidence for the idea that lexical/semantic
      knowledge is an important source of constraint on phonological coherence,
      ensuring that phonemes in familiar words are bound to each other and emerge
      together in recall.

PMID- 19114053
TI  - Stejnihagin, a novel snake metalloproteinase from Trimeresurus stejnegeri venom,
      inhibited L-type Ca2+ channels.
AB  - Snake venom metalloproteinases (SVMPs) mainly distribute in Crotalid and Viperid
      snake venom and are classified into the Reprolysin subfamily of the M12 family of
      metalloproteinases. Previous function investigations have suggested that SVMPs
      are the key toxins involved in a variety of snake venom-induced pathogenesis
      including systemic injury, local damage, hemorrhage, edema, hypotension,
      hypovolemia, inflammation and necrosis. However, up to now, there is no report on
      ion channels blocking activity about SVMPs. Here, from Trimeresurus stejnegeri
      venom we purified a component Stejnihagin containing a mixture of Stejnihagin-A
      and -B, with 86% sequences identity, both as members of SVMPs. In the study,
      whole-cell patch clamp and vessel tension measurement were employed to identify
      the effect of Stejnihagin on L-type Ca2+ channels and vessel contraction. The
      results show that Stejnihagin inhibited L-type Ca2+ channels in A7r5 cells with
      an IC50 about 37 nM and simultaneously blocked 60 mM K+-induced vessel
      contraction. Besides, the inhibitory effect of Stejnihagin on L-type Ca2+
      channels was also independent of the enzymatic activity. This finding offers new
      insight into the snake venom metalloproteinase functions and provides a novel
      pathogenesis of T. stejnegeri venom. Furthermore, it may also provide a clue to
      study the structure-function relationship of animal toxins and voltage-gated Ca2+
      channel.

PMID- 19114054
TI  - 1H NMR determination of beta-N-methylamino-L-alanine (L-BMAA) in environmental
      and biological samples.
AB  - A nuclear magnetic resonance (1H NMR) method for the determination of beta-N
      methylamino-L-alanine (L-BMAA) in environmental aqueous samples was developed and
      validated. L-BMAA is a neurotoxic modified amino acid that can be produced by
      cyanobacteria in aqueous environments. This toxin was extracted from samples by
      means of solid-phase extraction (SPE) and identified and quantified by 1H NMR
      without further derivatization steps. The lower limit of quantification (LLOQ)
      was 5 microg/mL. Good inter and intra-assay precision was also observed (relative
      standard deviation <8.5%) with the use of 4-nitro-DL-phenylalanine as an internal
      standard (IS). This method of 1H NMR analysis is not time consuming and can be
      readily utilized to monitor L-BMAA and confirm its presence in environmental and
      biological samples.

PMID- 19114055
TI  - Neurotoxicity of inverted-cone shaped lipids.
AB  - Many amphipatic molecules are characterized by an inverted-cone shape capable of
      altering the curvature and other properties of the plasma membrane of cells. We
      have recently shown that several lysophospholipids which have this shape impair
      nerve terminals by promoting neuroexocytosis and inhibiting endocytosis. This
      results in a bulging of neurites and nerve terminals and block of
      neurotransmission with paralysis of the neuromuscular junction. Here, we have
      determined the neurotoxicity of four inverted-cone shaped molecules of great
      interest because of their biological and pharmacological activities: miltefosine,
      perifosine, lysoPAF and lysophosphatidylcholine. These compounds were found to
      cause a complete, but reversible, paralysis of the nerve-hemidiaphragm
      preparation and to induce bulging of neurons in culture with entry of calcium
      from the external medium.

PMID- 19114057
TI  - Simplified lentivirus vector production in protein-free media using
      polyethylenimine-mediated transfection.
AB  - During the past 12 years, lentiviral vectors have emerged as valuable tools for
      transgene delivery because of their ability to transduce nondividing cells and
      their capacity to sustain long-term transgene expression. Despite significant
      progress, the production of high-titer high-quality lentiviral vectors is
      cumbersome and costly. The most commonly used method to produce lentiviral
      vectors involves transient transfection using calcium phosphate (CaP)-mediated
      precipitation of plasmid DNAs. However, inconsistencies in pH can cause
      significant batch-to-batch variations in lentiviral vector titers, making this
      method unreliable. This study describes optimized protocols for lentiviral vector
      production based on polyethylenimine (PEI)-mediated transfection, resulting in
      more consistent lentiviral vector stocks. To achieve this goal, simple production
      methods for high-titer lentiviral vector production involving transfection of HEK
      293T cells immediately after plating were developed. Importantly, high titers
      were obtained with cell culture media lacking serum or other protein additives
      altogether. As a consequence, large-scale lentiviral vector stocks can now be
      generated with fewer batch-to-batch variations and at reduced costs and with less
      labor compared to the standard protocols.

PMID- 19114056
TI  - Transfer of small interfering RNA by single-cell electroporation in cerebellar
      cell cultures.
AB  - RNA interference (RNAi) is a powerful means to investigate functions of genes
      involved in neuronal differentiation and degeneration. In contrast to widely used
      methods for introducing small interfering RNA (siRNA) into cells, recently
      developed single-cell electroporation has enabled transfer of siRNA into single
      and identified cells. To explore the availability of single-cell electroporation
      of siRNA in detail, we introduced siRNA against green fluorescent protein (GFP)
      into GFP-expressing Golgi and Purkinje cells in cerebellar cell cultures by
      single-cell electroporation using micropipettes. The temporal changes in the
      intensity of GFP fluorescence in the same electroporated cells were monitored in
      real-time up to 4 days after electroporation. Several parameters, including tip
      diameter and resistance of micropipettes, concentrations of siRNA and a
      fluorescent dye marker, voltage and time of pulses, were optimized to maximize
      both the efficacy of RNAi and the viability of the electroporated cells. Under
      the optimal conditions, transfer of GFP siRNA significantly reduced GFP
      fluorescence in the electroporated cells, whereas that of negative control siRNA
      had no effects. GFP siRNA was more efficient in Purkinje cells than in Golgi
      cells. The electroporated Purkinje cells were normal in their morphology,
      including elaborated dendrites. Thus, the single-cell electroporation of siRNA
      could be a simple but effective tool for silencing gene expression in individual
      cells in neuronal primary cultures. In addition, both gene-silencing and off
      target effects of siRNA introduced by this method may differ between neuronal
      cell types, and the parameters of single-cell electroporation should be optimized
      in each cell type.

PMID- 19114058
TI  - Use of a robotic RNA purification protocol based on the NucliSens easyMAG for
      real-time RT-PCR detection of hepatitis A virus in bottled water.
AB  - Hepatitis A virus (HAV) infection is the leading cause of acute viral hepatitis
      throughout the world. An important part of viral control is rapid detection of
      HAV in drinking water contaminated with feces. One critical step in HAV detection
      methods is sample preparation. The objective of this study was to test the
      efficacy of different approaches to extracting RNA from HAV-inoculated bottled
      water. The optimal method is based on viral concentration by filtration on
      membrane filters and elution of adsorbed viruses from filters before RNA
      extraction and RT-PCR amplification. In this approach, the commercially available
      NucliSens easyMAG bio-robot (Biomerieux) performs viral RNA purification with
      silica magnetic beads, which mediate purification of nucleic acids by binding
      them and allowing other substances to be washed away. A new rapid simplified
      NucliSens easyMAG-based approach is described and compared with the classical
      NucliSens easyMAG approach and with manual silica-based spin column purifications
      (Qiagen). The limit of detection (LOD) with the new rapid simplified NucliSens
      easyMAG approach was about 1PFU/1.5L against about 100PFU/1.5L using conventional
      sample treatments that included a concentration step using ultra-filtration.

PMID- 19114060
TI  - Distinct forms of prepulse inhibition disruption distinguishable by the
      associated changes in prepulse-elicited reaction.
AB  - Prepulse inhibition (PPI) of the acoustic startle reflex has been extensively
      employed as a test of sensorimotor gating or early attentional control in
      neuropsychiatric research, because a number of psychiatric conditions, including
      schizophrenia, exhibit PPI deficiencies. In both human and animal studies, PPI is
      commonly demonstrated by an attenuation of the acoustic startle reflex when the
      startle-inducing pulse stimulus is shortly preceded by a weak non-startling
      prepulse stimulus. This weakening of the startle reaction is attributed to, and
      therefore also provides an indirect measure of, the inhibition triggered by the
      perception of the prepulse stimulus. The relative ease in measuring the overt
      pulse-elicited startle reaction, in comparison with the relatively weak prepulse
      elicited reaction (PPER) has led to a near complete neglect of the latter in
      recent literature. However, the assumption that the prepulse used in PPI is non
      startling, does not imply that it is associated with no measurable responses. In
      fact the feasibility and reliability of obtaining such measures has been
      confirmed in both rodents and humans, and here we review the key findings derived
      from the direct evaluation of prepulse-elicited reaction in PPI, including under
      conditions that lead to PPI deficits. The theoretical implications and potential
      interpretative values of PPER are discussed. It is concluded that PPER should no
      longer be ignored; its emphasis may shed light on the kind of inhibition or
      gating dysfunction relevant to PPI disruption seen in pathological conditions
      including schizophrenia.

PMID- 19114059
TI  - No exit: targeting the budding process to inhibit filovirus replication.
AB  - The filoviruses, Ebola and Marburg, cause severe hemorrhagic fever in humans and
      nonhuman primates, with high mortality rates. Although the filovirus replication
      pathway is now understood in considerable detail, no antiviral drugs have yet
      been developed that directly inhibit steps in the replication cycle. One
      potential target is the filovirus VP40 matrix protein, the key viral protein that
      drives the budding process, in part by mediating specific virus-host interactions
      to facilitate the efficient release of virions from the infected cell. This
      review will summarize current knowledge of key structural and functional domains
      of VP40 believed to be necessary for efficient budding of virions and virus-like
      particles. A better understanding of the structure and function of these key
      regions of VP40 will be crucial, as they may represent novel and rational targets
      for inhibitors of filovirus egress.

PMID- 19114061
TI  - The time course of Chinese riddles solving: evidence from an ERP study.
AB  - The electrophysiological correlates of successful insight and routine problem
      solving were studied in 12 healthy subjects using high-density event-related
      potentials (ERPs). Results showed that insight problems elicited a more negative
      ERP deflection (N300-800) than did routine problems between 300 and 800 ms, and a
      more negative ERP deflection (N1200-1500) than did routine problems between 1200
      and 1500 ms over the fronto-central scalp regions. However, insight problems
      elicited a more positive ERP deflection (P300-800) than did routine problems
      between 300 and 800 ms, and a more positive ERP deflection (P1200-1500) than did
      routine problems between 1200 and 1500 ms over the parieto-occipital scalp
      regions. Dipole source analysis showed that two dipoles were located in the
      anterior cingulate cortex (ACC) and the parahippocampal gyrus between 300 and 800
      ms, and two dipoles were located in the parahippocampal gyrus and the superior
      frontal gyrus between 1200 and 1500 ms. We discussed the implications of these
      ERP components in insight problem solving.

PMID- 19114062
TI  - Evidence that J-binding protein 2 is a thymidine hydroxylase catalyzing the first
      step in the biosynthesis of DNA base J.
AB  - The genomic DNA of kinetoplastid parasites contains a unique modified base, beta
      d-glucosyl-hydroxymethyluracil or base J. We recently reported that two proteins,
      called J-binding protein (JBP) 1 and 2, which regulate the levels of J in the
      genome, display features of the family of Fe(II)-2-oxoglutarate dependent
      dioxygenases and are likely to be the enzymes catalyzing the first step in J
      biosynthesis. In this study, we examine the effects of replacing the four
      conserved residues critical for the activity of this class of enzymes on the
      function of Leishmania tarentolae JBP2. The results show that each of these four
      residues is indispensable for the ability of JBP2 to stimulate J synthesis, while
      mutating non-conserved residues has no consequences. We conclude that JBP2, like
      JBP1, is in all probability a thymidine hydroxylase involved in the biosynthesis
      of base J.

PMID- 19114063
TI  - Impaired neurogenesis in embryonic spinal cord of Phgdh knockout mice, a serine
      deficiency disorder model.
AB  - Mutations in the d-3-phosphoglycerate dehydrogenase (PHGDH; EC 1.1.1.95) gene,
      which encodes an enzyme involved in de novol-serine biosynthesis, are shown to
      cause human serine deficiency disorder. This disorder has been characterized by
      severe neurological symptoms including congenital microcephaly and psychomotor
      retardation. Our previous work demonstrated that targeted disruption of mouse
      Phgdh leads to a marked decrease in serine and glycine, severe growth retardation
      of the central nervous system, and lethality after embryonic day 13.5. To clarify
      how a serine deficiency causes neurodevelopmental defects, we characterized
      changes in metabolites, gene expression and morphological alterations in the
      spinal cord of Phgdh knockout mice. BeadChip microarray analysis revealed
      significant dysregulation of genes involved in the cell cycle. Ingenuity Pathway
      Analysis also revealed a significant perturbation of regulatory networks that
      operate in the cell cycle progression. Moreover, morphological examinations of
      the knockout spinal cord demonstrated a marked deficit in dorsal horn neurons.
      Radial glia cells, native neural stem/progenitor cells, accumulated in the dorsal
      ventricular zone, but they did not proceed to a G(0)-like quiescent state. The
      present integrative study provides in vivo evidence that normal cell cycle
      progression and subsequent neurogenesis of radial glia cells are severely
      impaired by serine deficiency.

PMID- 19114064
TI  - Low molecular weight plant extract induces metabolic changes and the secretion of
      extracellular enzymes, but has a negative effect on the expression of the type
      III secretion system in Xanthomonas campestris pv. campestris.
AB  - Xanthomonas campestris pathovar campestris (Xcc) is a plant pathogenic bacterium
      and as such has to adapt to a variety of environments. During the course of
      disease, Xcc colonizes the surface of its host, infects the xylem in the early
      stages, and develops a fully saprophytic life-style, aided by secreted
      degradative enzymes, in the late stages. To get some insight into this complex
      regulation, Xcc was cultivated in the presence of low molecular weight host plant
      extract (<10 kDa). From this experiments it could be observed, that malate and
      sucrose are taken up preferably in such an environment. Furthermore, it was
      demonstrated, that the plant extract has a negative effect on the gene expression
      of the hrp-gene cluster, although the activator hrpG was induced. Also, the
      secretion of degradative enzymes was shown to be upregulated. These observations
      indicate, that a low molecular weight plant extract (<10 kDa) is a sufficient
      signal to regulate metabolic pathways and the secretion of enzymes relevant for
      the development of virulence in Xanthomonas, but has a negative effect on the
      expression of genes involved in type-III secretion.

PMID- 19114065
TI  - Diet-related restrictive parenting practices. Impact on dietary intake of 2-year
      old children and interactions with child characteristics.
AB  - This study examined the relationship between diet-related parenting practices,
      parental characteristics, child characteristics, and 2-year-old child's dietary
      intake. Cross-sectional data (N=2578) originated from the KOALA Birth Cohort
      Study. Principal component analyses revealed two restrictive parenting practice
      clusters: a cluster characterized by prohibition of the intake of various snacks
      and soft drinks, and a separate cluster characterized by prohibition of cookies
      and cake. Regression analyses showed that these clusters were related to the
      children's behavioural style (i.e. oppositional, depressive and/or aggressive
      behaviour) and to educational level, age and alternative lifestyle of the mother.
      The clusters also had a favourable influence on dietary intake (i.e. restrictive
      parenting practices were related to less consumption of the restricted
      (unhealthy) items and higher consumption of items considered to be healthy),
      which was moderated by child characteristics. The parenting practices showed a
      stronger association with dietary intake in children with a favourable
      behavioural style (i.e. non-depressed, low anxious, low overactive), a favourable
      eating style or a lower BMI. The findings suggest opportunities for preventive
      interventions focussing on parents of young children, and indicate that different
      approaches to parenting practice interventions are needed for different types of
      children.

PMID- 19114066
TI  - Molecular mechanisms underlying cochlear degeneration in the tubby mouse and the
      therapeutic effect of sulforaphane.
AB  - As with Usher syndrome observed in humans, the two main phenotypes of the tubby
      mouse are progressive hearing loss and retinal degeneration. Yet, the mechanism
      underlying the tub-related cochlear degeneration is still unclear. The
      reduction/oxidation (redox) imbalance in the cell is related to many kinds of
      diseases. This study examined expressions of thioredoxin (Trx) and Trx reductase
      (TrxR), an important redox system in the cell, and the related upstream and
      downstream proteins of the Trx/TrxR in the tubby mouse cochlea. This report also
      examined the therapeutic effect of sulforaphane (SF) on the cochlear
      degeneration, which showed a protective effect on the tub-related retinal
      degeneration in our previous report. The results showed that the tub-mutation
      resulted in a significant suppression of Trx and TrxR expressions. Expression
      level of Nrf2 (NFE2 related factor 2), a transcription factor that regulates
      expression of Trx and TrxR and others, was also suppressed in the tubby mouse
      cochlea. Furthermore, a lowered level of activated extracellular signal-regulated
      kinase (p-ERK) was observed in the tubby mouse cochlea. In contrast, caspase-3
      expression and activity were enhanced in the tubby mouse, suggesting apoptotic
      cell death. The tub-related molecular alterations in the cochlea were prevented
      by chronic treatment with SF. As a result, the SF-treatment significantly delayed
      the tub-related cochlear degeneration. Other unknown proteins may contribute to
      tubby-related degeneration because Nrf2 regulates many other antioxidants besides
      Trx/TrxR and sulforaphane did not prevent cochlear degeneration completely
      although it completely prevented alterations of Nrf2 and Trx/TrxR.

PMID- 19114067
TI  - Effect of pranoprofen on endoplasmic reticulum stress in the primary cultured
      glial cells.
AB  - Endoplasmic reticulum (ER) stress has been implicated in the pathogenesis of CNS
      diseases such as Alzheimer's disease, Parkinson's disease, and cerebral ischemia.
      In the present study, we investigated the effect of pranoprofen, a non-steroidal
      anti-inflammatory drug (NSAID), on endoplasmic reticulum stress responses in the
      primary cultured glial cells. Pranoprofen inhibited ER stress-induced glucose
      regulated protein 78 (GRP78) expression, an ER-localized molecular chaperon.
      Moreover, pranoprofen inhibited ER stress-induced CCAAT/enhancer-binding protein
      homologous protein (CHOP) expression, an apoptotic transcription factor. ER
      stress-induced phosphorylation of alpha-subunit of eukaryotic initiation factor-2
      (eIF2alpha) has been reported to be involved in CHOP induction. Interestingly,
      pranoprofen alone induced eIF2alpha phosphorylation, which was further increased
      by ER stress. On the other hand, ER stress-induced X-box-binding protein 1 (XBP
      1) splicing was inhibited in pranoprofen-treated cells. Thus, the inhibitory
      effect of pranoprofen on ER stress-related genes (GRP78 and CHOP) would be
      mediated through the inhibition of XBP-1 splicing. In the present study,
      pranoprofen has been suggested to affect ER stress. The present results may have
      important implications for understanding ER stress-related diseases.

PMID- 19114069
TI  - Ghrelin alters postnatal endocrine secretion and behavior in mouse offspring.
AB  - Maternal bioactive substances, such as hormones and neuropeptides, are thought to
      be essential for fetal development. Recently, ghrelin, a gastrointestinal
      peptide, has been shown to pass through the rat placenta. The ghrelin receptor,
      growth hormone secretagogue receptor (GHS-R), has been shown to be expressed in
      the rat fetal central nervous system, and plasma ghrelin levels are related to
      birth weight in the rodent and human. In the present study, we report a role of
      maternal ghrelin in mouse fetal brain development. When ghrelin was administrated
      to pregnant mice, pups exhibited suppression of exploratory behavior in an open
      field (OF) test. Control pups, however, remained for longer periods of time in
      the center area, correlating with exploratory behavior. Basal corticotropin
      releasing hormone (CRH) plasma levels were greater in pups from ghrelin-treated
      dams, and did not change in response to acute restraint stress. Moreover, reduced
      growth hormone secretagogue receptor and neuropeptide Y mRNA expression was
      observed in the hypothalamus at postnatal day 3 and remained until 16 weeks of
      age. In addition, under physiological condition, increased maternal ghrelin
      plasma levels following repeated restraint stress to the dam had effect on the
      increase in fetal plasma acyl ghrelin levels. These results suggest that maternal
      ghrelin affect fetal plasma ghrelin levels and alters endocrine systems and
      behaviors of offspring.

PMID- 19114068
TI  - Cell cycle re-entry mediated neurodegeneration and its treatment role in the
      pathogenesis of Alzheimer's disease.
AB  - As one of the earliest pathologic changes, the aberrant re-expression of many
      cell cycle-related proteins and inappropriate cell cycle control in specific
      vulnerable neuronal populations in Alzheimer's disease (AD) is emerging as an
      important component in the pathogenesis leading to AD and other neurodegenerative
      diseases. These events are clearly representative of a true cell cycle, rather
      than epiphenomena of other processes since, in AD and other neurodegenerative
      diseases, there is a true mitotic alteration that leads to DNA replication. While
      the exact role of cell cycle re-entry is unclear, recent studies using cell
      culture and animal models strongly support the notion that the dysregulation of
      cell cycle in neurons leads to the development of AD-related pathology such as
      hyperphosphorylation of tau and amyloid-beta deposition and ultimately causes
      neuronal cell death. Importantly, cell cycle re-entry is also evident in mutant
      amyloid-beta precursor protein and tau transgenic mice and, as in human disease,
      occurs prior to the development of the pathological hallmarks, neurofibrillary
      tangles and amyloid-beta plaques. Therefore, the study of aberrant cell cycle
      regulation in model systems, both cellular and animal, may provide extremely
      important insights into the pathogenesis of AD and also serve as a means to test
      novel therapeutic approaches.

PMID- 19114070
TI  - Maternal supply of BDNF to mouse fetal brain through the placenta.
AB  - Gastrointestinal peptides and hormones are known to penetrate through the utero
      placental barrier and regulate fetal development. In the present study, we tested
      permeation of maternal brain-derived neurotrophic factor (BDNF) to fetuses, using
      BDNF-gene deficient mice and exogenous BDNF administration. At embryonic day 13.5
      (E13.5)-14.5, BDNF protein concentrations in the fetal brain of BDNF homozygous
      null mutant (bdnf (-/-)) were comparable to the levels seen in wild-type fetuses.
      After E17.5, BDNF protein levels in bdnf (-/-) fetal brain were still detectable
      but its levels were significantly decreased below those in wild-type brain. When
      recombinant BDNF protein was injected into pregnant wild-type mice carrying E14.5
      embryos, BDNF protein levels in fetal brain were elevated dose-dependently. These
      findings suggest that maternal BDNF reaches the fetal brain through utero
      placental barrier and might contribute to its development.

PMID- 19114071
TI  - Involvement of retinoic acid signaling in goldfish optic nerve regeneration.
AB  - Recently, we identified a retina-specific retinol-binding protein, purpurin, as a
      trigger molecule in the early stage of goldfish optic nerve regeneration.
      Purpurin protein was secreted by photoreceptors to injured ganglion cells, at 2-5
      days after optic nerve injury. Purpurin bound to retinol induced neurite
      outgrowth in retinal explant cultures and retinoic acid (RA) had a comparable
      effect on neurite outgrowth. These results indicate that purpurin acts as a
      retinol transporter and facilitates conversion of retinol to RA. Intracellularly,
      RA is transported into the nucleus with cellular retinoic acid-binding protein
      IIb (CRABPIIb) and binds with retinoic acid receptor alpha (RARalpha) as a
      transcriptional regulator of target genes. Here, we investigated the RA signaling
      through RA synthesis to RARalpha in the goldfish retina during optic nerve
      regeneration by RT-PCR. Retinaldehyde dehydrogenase 2 (RALDH2; an RA synthetic
      enzyme) mRNA was increased by 2.7-fold in the retina at 7-10 days and then
      gradually decreased until 40 days after nerve injury. In contrast, cytochrome
      P450 26a1 (CYP26a1; an RA degradative enzyme) mRNA was decreased to less than
      half in the retina at 5-20 days and then gradually returned to the control level
      by 40 days after nerve injury. CRABPIIb mRNA was increased by 1.5-fold in the
      retina at 10 days after axotomy, RARalphaa mRNA was increased by 1.8-fold in the
      retina at 10 days after axotomy. The cellular changes in the RA signaling
      molecules after optic nerve injury were almost all located in the ganglion cells,
      as evaluated by in situ hybridization. The present data described for the first
      time that RA signaling through RALDH2 and CRABPIIb to RARalpha was serially
      upregulated in the ganglion cells at 7-10 days just after the purpurin induction.
      Therefore, we conclude that the triggering action of purpurin on optic nerve
      regeneration is mediated by RA signaling pathway.

PMID- 19114073
TI  - Different effects of probiotic species/strains on infections in preschool
      children: A double-blind, randomized, controlled study.
AB  - Treatment and prevention of pediatric infectious diseases of three commercial
      probiotic products were evaluated by a double-blind, randomized, controlled
      trial. Test subjects under age 5, 1062 in total, were distributed randomly into
      four groups. This investigation showed that L. casei rhamnosus can control
      bacterial, viral and respiratory infections; a multi-species probiotic reduced
      gastrointestinal disease significantly. Long-term consumption of L. rhamnosus T
      cell-1 decreased the incidence of bacterial infection.

PMID- 19114072
TI  - Role of retinal glial cells in neurotransmitter uptake and metabolism.
AB  - In addition to photoreceptors and neurons, glial cells (in particular Muller
      cells) contribute to the removal and metabolization of neurotransmitters in the
      neural retina. This review summarizes the present knowledge regarding the role of
      retinal glial cells in the uptake of glutamate, N-acetylaspartylglutamate, gamma
      aminobutyric acid, glycine, and d-serine, as well as the degradation and removal
      of purinergic receptor agonists. Some major pathways of glutamate metabolism in
      Muller cells are described; these pathways are involved in the glutamate
      glutamine cycle of the retina, in the defense against oxidative and nitrosative
      stress via the production of glutathione, and in the production of substrates for
      the neuronal energy metabolism. In addition, the developmental regulation of the
      major glial glutamate transporter, GLAST, and of the glia-specific enzyme
      glutamine synthetase is described, as well as the importance of a malfunction and
      even reversal of glial glutamate transporters, and a downregulation of the
      glutamine synthetase, as pathogenic factors in different retinopathies.

PMID- 19114074
TI  - Infection with a low virulent Mycoplasma hyopneumoniae isolate does not protect
      piglets against subsequent infection with a highly virulent M. hyopneumoniae
      isolate.
AB  - The study aimed to evaluate the effect of an infection with low virulent isolates
      of M. hyopneumoniae (LV1 and LV2) on the subsequent infection with a highly
      virulent isolate (HV). Fifty-five, 3-week-old piglets free of M. hyopneumoniae
      were randomly allocated to 6 different groups. At 4 weeks of age (D0), groups LV1
      HV and LV1 were intratracheally inoculated with LV1, groups LV2-HV and LV2 with
      LV2, and group HV with sterile culture medium. Four weeks later (D28), the pigs
      of these different groups were either intratracheally inoculated with the highly
      virulent isolate (groups LV1-HV, LV2-HV, HV) or with sterile culture medium
      (groups LV1 and LV2). A negative control group consisted of pigs inoculated with
      sterile culture medium on D0 and D28. All animals were necropsied at 28 days
      after the second inoculation (D56). Clinical symptoms were evaluated daily using
      a respiratory disease score (RDS). After necropsy, macroscopic and
      histopathological lung lesions were quantified and immunofluorescence (IF)
      testing on lung tissue and nested PCR on BAL fluid were performed for the
      detection of M. hyopneumoniae. Disease signs and lung lesions were not observed
      in pigs of the negative control group. In the other groups, there were no or only
      very mild clinical symptoms from D0 until D28. A significant increase in the
      average RDS values was, however, observed during D28-D56, especially in groups
      LV1-HV (1.48) and LV2-HV (1.49), in group HV (0.79), and to a lesser extent in
      groups LV1 (0.50) and LV2 (0.65) (P<0.05). The clinical symptoms during D28-D56,
      the lung lesions and intensity of IF staining were more pronounced in groups LV1
      HV, LV2-HV and HV compared to groups LV1 and LV2. All pigs, except those from the
      negative control group, were positive on IF testing and PCR at D56. The present
      study demonstrates that pigs inoculated with low virulent isolates of M.
      hyopneumoniae are not protected against a subsequent infection with a highly
      virulent isolate 4 weeks later and may even develop more severe disease signs.
      This indicates that subsequent infections with different M. hyopneumoniae
      isolates may lead to more severe clinical disease in a pig herd.

PMID- 19114075
TI  - Spray-dried powders of starch and crosslinked poly(acrylic acid) as carriers for
      nasal delivery of inactivated influenza vaccine.
AB  - Mucosal vaccination has several advantages over parenteral vaccination. In this
      study, viscosity-enhancing mucosal delivery systems for the induction of an
      adaptive immune response against viral antigen were investigated. Powder
      formulations based on spray-dried mixtures of starch (Amioca)/poly(acrylic acid)
      (Carbopol 974P) in different ratios were used as carriers of the viral antigen. A
      comparison of these formulations for intranasal delivery of heat-inactivated
      influenza virus combined with LTR192G adjuvant was made in vivo in a rabbit
      model. Individual rabbit sera were tested for seroconversion against
      hemagglutinin (HA), the major surface antigen of influenza. The powder vaccine
      formulations were able to induce systemic anti-HA IgG responses. The presence of
      Carbopol 974P improved the kinetics of the immune responses and the level of IgG
      titers in a dose-dependent way which was correlated with moderately irritating
      capacities of the formulation. In contrast, mucosal IgA responses were not
      detected. In conclusion, it was demonstrated that the use of bioadhesive carriers
      based on Amioca starch and poly(acrylic acid) facilitates the induction of a
      systemic anti-HA antibody response after intranasal vaccination with a whole
      virus influenza vaccine.

PMID- 19114077
TI  - Intradermal vaccination of pigs against FMD with 1/10 dose results in comparable
      vaccine efficacy as intramuscular vaccination with a full dose.
AB  - The aim of this study was to investigate whether intradermal (ID) vaccination
      against foot-and-mouth disease (FMD) is suitable as an alternative for the
      usually used intramuscular (IM) route. We compared vaccine efficacy in groups of
      pigs in which vaccine administration differed with respect to antigen payload of
      the vaccine, administrated volume and administration route. When compared with
      pigs that were IM vaccinated with a full dose vaccine with a standard antigen
      payload, pigs vaccinated ID with 1/10 dose of the same vaccine were equally
      protected against clinical disease and subclinical virus shedding. The ID
      vaccinated pigs were protected against virus shedding at a significant lower VN
      titre as compared to IM vaccinated pigs, suggesting that immune responses other
      than neutralising antibodies also contributed to protection. We conclude that the
      ID route might be a good alternative for IM application, as ID application might
      induce a very efficient immunological response against FMD and, moreover, because
      the dose required by the ID route is lower compared to the IM route, ID
      application may reduce the production costs per dose of FMD vaccine markedly.

PMID- 19114076
TI  - Antibody response and plasma Abeta1-40 levels in young Microcebus murinus
      primates immunized with Abeta1-42 and its derivatives.
AB  - We have been developing Abeta derivative vaccines with the objective to improve
      the safety of Abeta targeting immunotherapy. Our Abeta homologs are designed to
      have less direct toxicity and to produce a modified immune response compared to
      Abeta. In extensive mouse studies, all our vaccines have improved cognition in
      transgenic mice while eliciting different immune responses and reducing brain
      amyloid burden to a variable degree. While we are continuing to characterize
      these vaccines in mice, in preparation for studies in old primates and for human
      trials we assessed their effect in young lemur primates (n=25) that with age
      develop Abeta plaques and tau aggregates as seen in Alzheimer's disease. In the
      primates, all the peptides administered with alum adjuvant elicited a moderate to
      robust anti-Abeta IgM response. Abeta1-42, K6Abeta1-30 and K6Abeta1
      30[E(18)E(19)] resulted in a high anti-Abeta IgG response, whereas Abeta1
      30[E(18)E(19)] produced a weaker more variable IgG titer. Notably, 22 weeks after
      the 3rd immunization, IgM and IgG levels in derivative-vaccinated primates were
      similar to preimmune values whereas Abeta1-42 treated primates maintained a
      moderate IgG titer. The increase in antibodies that recognized Abeta1-40 often
      correlated with increase in Abeta1-40 in plasma, which suggests that the
      antibodies were binding to Abeta in vivo. Interestingly, significant transient
      weight gain was observed (K6Abeta1-30-, Abeta1-30[E(18)E(19)]- and Abeta1-42
      treated) or a trend in the same direction (K6Abeta1-30[E(18)E(19)]-treated,
      adjuvant controls) following the injections. Based on these findings, we have
      chosen K6Abeta1-30 for immunizations in old primates as the antibody response to
      this vaccine was less variable compared to other Abeta derivatives. Our present
      findings indicate that most of our Abeta derivatives elicit a substantial
      antibody response in primates, and importantly this effect is reversible which
      enhances the safety profile of our approach.

PMID- 19114078
TI  - Willingness of healthcare workers to accept voluntary stockpiled H5N1 vaccine in
      advance of pandemic activity.
AB  - Healthcare workers may be at risk during the next influenza pandemic. Priming
      with stockpiled vaccine may protect staff and reduce nosocomial transmission.
      Despite campaigns to increase seasonal influenza vaccine coverage, uptake among
      healthcare workers is generally low; creating uncertainty whether they would
      participate in pre-pandemic vaccine programmes. We conducted a cross-sectional
      questionnaire survey of healthcare workers in a UK hospital during, and 6 months
      after, a period of media reporting of an H5N1 outbreak at a commercial UK poultry
      farm. A total of 520 questionnaires were returned, representing 20% of frontline
      workforce. More respondents indicated willingness to accept stockpiled H5N1
      vaccine during the period of media attention than after (166/262, 63.4% vs.
      134/258, 51.9%; p=0.009). Following multivariate analysis, factors associated
      with willingness to accept H5N1 vaccine included: previous seasonal vaccine (OR
      6.2, 95% CI 3.0-12.8, p<0.0001), awareness of occupational seasonal vaccine
      campaigns (OR 2.2, 95% CI 1.4-3.5, p=0.001), belief that seasonal vaccine
      benefits themselves (OR 2.5, 95% CI 1.6-4.0, p<0.0001) or the hospital (OR 3.6,
      95% CI 2.3-5.8, p<0.0001), belief that pandemic risk is high/moderate (OR 14.1,
      95% CI 7.6-26.1, p<0.0001) and would threaten healthcare workers (OR 2.9, 95% CI
      1.8-4.5, p<0.0001). Those who would not accept vaccine (220 respondents, 42.7%)
      if offered before the pandemic do not perceive pandemic influenza as a serious
      threat, and have concerns regarding vaccine safety. A majority of healthcare
      workers are amenable to accept stockpiled H5N1 vaccine if offered in advance of
      pandemic activity.

PMID- 19114079
TI  - New approach on the development of a mucosal vaccine against strangles: Systemic
      and mucosal immune responses in a mouse model.
AB  - Streptococcus equi subspecies equi affects animals of Equidae family and is the
      causative agent of strangles, an acute, extremely contagious and deadly disease.
      Prolonged periods of protection associated to absence of serious adverse
      reactions were not yet achieved. Thus, this experimental work is focused on the
      study of mucosal, humoral and cellular immune responses developed in a mouse
      model, after the intranasal administration of S. equi antigens associated by
      adsorption or encapsulation to poly(lactic acid) nanospheres, modified by
      mucoadhesive polymers and absorption enhancers. Particles fitted the nanometer
      range and proteins integrity and antigenicity were not affected. PLA nanospheres
      induced a mixed Th1 and Th2 response, being therefore potential carriers for the
      delivery of S. equi antigens.

PMID- 19114080
TI  - Safe vaccination of children with a virosomal adjuvanted influenza vaccine.
AB  - A post-marketing study was conducted in 26 paediatric practices in Germany to
      collect safety information on the virosomal adjuvanted influenza vaccine Inflexal
      V (in Germany marketed as Infectovac Flu). Children aged 6 months to 6 years
      received one or two doses. Adverse events were documented by parents/legal
      guardians in a questionnaire for four days after vaccination. The rates of
      adverse events were low: 14% of vaccine exposures were associated with systemic
      and 25% with local adverse events. Most symptoms were mild to moderate and
      resolved within a few days. Nearly 100% of parents/legal guardians would agree to
      have their child vaccinated again with Inflexal V. Vaccination with Inflexal V
      was safe, well tolerated and highly accepted by parents/legal guardians.

PMID- 19114081
TI  - Further evaluation of the utility of "sliding window" FASTA in predicting cross
      reactivity with allergenic proteins.
AB  - FAO/WHO has recommended that IgE cross-reactivity between a transgenic protein
      and allergen be considered when there is greater than 35% identity over a sliding
      "window" of 80 amino acids. In a previous work, we evaluated the false positive
      and negative rates observed using the FAO/WHO criteria versus conventional, whole
      protein FASTA analyses [Ladics, G.S., Bannon, G.A., Silvanovich, A., Cressman,
      R.F., 2007. Comparison of conventional FASTA identity searches with the 80 amino
      acid sliding window FASTA search for the elucidation of potential identities to
      known allergens. Mol. Nutr. Food Res. 51 (8), 985-998]. A number of protein
      sequence datasets were used as queries against the FARRP 7 allergen database.
      Results indicated that conventional FASTA analysis produced fewer false positives
      then the "sliding window" search proposed by FAO/WHO. Further, both methods were
      able to identify the potential for cross-reactivity between the Bet v 1 family of
      proteins, indicating that the conventional FASTA search possessed sufficient
      sensitivity. Recently, collections of protein sequences from multiple crop
      species (corn, soy, barley, lettuce, sugar beets, and spinach) were subjected to
      the same screen against the FARRP7 allergen dataset. In all cases, the
      conventional FASTA search returned fewer above threshold matches than the sliding
      window search. Examination of the matches not recognized by the conventional
      search revealed two scenarios: (1) "true" false positives consisting of low
      statistical significance (as measured by E score, i.e., a measure of the
      potential random occurrence of aligned sequences used to evaluate the
      significance of an observed alignment) alignments not contained in the
      conventional FASTA outputs, and (2) above-threshold sliding window alignments
      that fell below the 35% identity threshold with the conventional FASTA analysis.
      Although some alignments within this second group were between regions of low
      sequence complexity, where there was little/no change in E score, the majority of
      the alignments displayed more significance (lower E scores) under the
      conventional FASTA algorithm, yet did not meet the threshold defined by FAO/WHO.
      These data question the utility of the FAO/WHO recommended sliding window FASTA
      compared to the traditional whole sequence FASTA analysis coupled with
      appropriate statistical analysis.

PMID- 19114082
TI  - Purple sweet potato color attenuates oxidative stress and inflammatory response
      induced by d-galactose in mouse liver.
AB  - The hepatoprotective effects of purple sweet potato color (PSPC), which is
      natural anthocyanin food colors, have been well demonstrated in many studies.
      Nevertheless, little work has been done to clarify the detailed mechanism of
      hepatoprotective effects of PSPC. This study was designed to explore whether PSPC
      protected mouse liver from d-gal-induced injury by attenuating oxidative stress
      or suppressing inflammation. The histology changes of mouse liver was assessed by
      hematoxylin and eosin staining. The results showed that PSPC could effectively
      suppress the d-gal-induced histology changes including structure damage and
      leucocyte infiltration in mouse liver. Oxidative stress and antioxidant status in
      mouse liver were also analysed. The results showed that PSPC could largely
      attenuate the d-gal-induced MDA increasing and could markedly renew the
      activities of Cu, Zn-SOD, CAT and GPx in the livers of d-gal-treated mice.
      Furthermore, the results of western blot analysis showed that PSPC could inhibit
      the upregulation of the expression of NF-kappaB p65, COX-2 and iNOS caused by d
      gal. In conclusion, our data suggested that PSPC could protect the mouse liver
      from d-gal-induced injury by attenuating lipid peroxidation, renewing the
      activities of antioxidant enzymes and suppressing inflammatory response. This
      study provided novel insights into the mechanisms of PSPC in the protection of
      the liver.

PMID- 19114083
TI  - Alterations in gene expression of glutamate receptors and exocytosis-related
      factors by a hydroxylated-polychlorinated biphenyl in the developing rat brain.
AB  - Polychlorinated biphenyls (PCBs), major environmental hormonally active agents,
      are metabolized into hydroxylated PCBs in the liver to facilitate excretion. Some
      of hydroxylated PCBs also have potencies disturbing endogenous hormonal
      activities at least in vitro. Hormonal activities of hydroxylated PCBs raise a
      possibility of their interfering with normal brain development which is strictly
      regulated by endogenous hormones. We investigated whether and how prenatal
      exposure to a congener of hydroxylated PCBs (4-OH-2',3,3',4',5'-penta CB; 4-OH
      PCB106) having activities to disrupt thyroid hormone-dependent signals in vitro
      could perturb normal gene expression in the developing brain in vivo. Pregnant
      rats were exposed to 4-OH-PCB106 subcutaneously at the dose of 1.0mg/(kgday) from
      day 7 of gestation to postnatal day 1. Then three brain regions (cerebral cortex,
      hippocampus and striatum) were obtained from offspring on postnatal day 1 and
      subjected to further gene expression analyses. Comprehensive analyses of mRNA
      expression by oligo DNA microarrays and subsequent validations by quantitative RT
      PCR revealed that prenatal exposure to 4-OH-PCB106 affected mRNA expression of
      glutamate receptors as well as that of thyroid hormone-responsive genes in region
      specific manners. Concomitantly 4-OH-PCB106 exposure increased mRNA expression of
      genes related to exocytosis in the three brain regions. These results raise the
      possibility that prenatal exposure to some hydroxylated PCBs with thyroid hormone
      disrupting potencies leads to abnormal brain development via perturbations on the
      expression of genes involved in glutamatergic neurotransmission.

PMID- 19114084
TI  - Patterns of some extracellular matrix gene expression are similar in cells from
      cleft lip-palate patients and in human palatal fibroblasts exposed to diazepam in
      culture.
AB  - Prenatal exposure to diazepam, a prototype sedative drug that belongs to
      Benzodiazepines, can lead to orofacial clefting in human newborns. By using real
      time PCR, in the present study we investigated whether diazepam elicits gene
      expression alterations in extracellular matrix (ECM) components, growth factors
      and gamma-aminobutyric acid receptor (GABRB3), implicated in the coordinate
      regulation of palate development. Palate fibroblasts were treated with diazepam
      (Dz-N fibroblasts) and compared to cleft lip-palate (CLP) fibroblasts obtained
      from patients with no known exposure to diazepam or other teratogens. Untreated
      fibroblasts from non-CLP patients were used as control. The results showed
      significant convergences in gene expression pattern of collagens, fibromodulin,
      vitronectin, tenascin C, integrins and metalloprotease MMP13 between Dz-N and CLP
      fibroblasts. Among the growth factors, constitutive Fibroblast Growth Factor 2
      (FGF2) was greatly enhanced in Dz-N and CLP fibroblasts and associated with a
      higher reduction of FGF receptor. Transforming Growth Factor beta 3 (TGFbeta(3))
      resulted up-regulated in CLP fibroblasts and decreased in Dz-N fibroblasts. We
      found phenotypic differences exhibited by Dz-N and CLP fibroblasts in GABRB3 gene
      regulation, so further studies are necessary to determine whether GABAergic
      system could be involved in the development of diazepam mediated CLP phenotype.
      Taken together the results elucidate the molecular mechanisms underlying possible
      toxicology effects induced by diazepam. Counselling of women on the safety of
      diazepam exposure is clinically important, also for the forensic consequences.

PMID- 19114085
TI  - Carcinogenesis studies of cresols in rats and mice.
AB  - Cresols, monomethyl derivatives of phenol, are high production chemicals with
      potential for human exposure. The three isomeric forms of cresol are used
      individually or in mixtures as disinfectants, preservatives, and solvents or as
      intermediates in the production of antioxidants, fragrances, herbicides,
      insecticides, dyes, and explosives. Carcinogenesis studies were conducted in
      groups of 50 male F344/N rats and 50 female B6C3F1 mice exposed to a 60:40
      mixture of m- and p-cresols (m-/p-cresol) in feed. Rats and mice were fed diets
      containing 0, 1500, 5000, or 15,000 ppm and 0, 1000, 3000, or 10,000 ppm,
      respectively. Survival of each exposed group was similar to that of their
      respective control group. Mean body weight gains were depressed in rats exposed
      to 15,000 ppm and in mice exposed to 3000 ppm and higher. A decrease of 25% over
      that of controls for the final mean body weight in mice exposed to 10,000 ppm
      appeared to be associated with lack of palatability of the feed. A marginally
      increased incidence of renal tubule adenoma was observed in the 15,000-ppm
      exposed rats. The increased incidence was not statistically significant, but did
      exceed the range of historical controls. No increased incidence of hyperplasia of
      the renal tubules was observed; however, a significantly increased incidence of
      hyperplasia of the transitional epithelium associated with an increased incidence
      of nephropathy was observed at the high exposure concentration. The only
      significantly increased incidence of a neoplastic lesion related to cresol
      exposure observed in these studies was that of squamous cell papilloma in the
      forestomach of 10,000-ppm-exposed mice. A definitive association with irritation
      at the site-of-contact could not be made because of limited evidence of injury to
      the gastric mucosa at the time of necropsy. However, given the minimal chemical
      related neoplastic response in these studies, it was concluded that there was no
      clear evidence of carcinogenicity in male rats or female mice exposed to the
      cresol mixture.

PMID- 19114086
TI  - Purification and characterization of recombinant human mineralocorticoid
      receptor.
AB  - The mineralocorticoid receptor (MR) plays a critical role in the maintenance of
      electrolyte homeostasis and blood pressure via direct effects on the distal
      nephron and the cardiovascular system. The MR also has an important role in the
      pathology of cardiovascular disease, particularly heart failure, and is therefore
      an attractive therapeutic target. However, renal side effects limit its use in
      the clinic. Previous studies of MR molecular pharmacology have been performed on
      its isolated ligand-binding domain (LBD); however, current evidence suggests that
      nuclear receptor LBDs behave differently in isolation, than in the context of the
      full-length receptor. To date, technical issues have precluded production of full
      length MR, thereby preventing molecular and structural studies of the MR LBD in
      its natural context. Here, we describe expression and purification of full-length
      human MR (hMR). hMR was expressed in Sf9 insect cells with an N-terminal
      biotinylated (bt)-tag, and stabilised by addition of ligand. bt-hMR exhibited
      ligand-binding and transactivation properties similar to that of the native
      protein. Affinity purification using an avidin matrix yielded approximately
      120mug MR protein from 0.5lt Sf9 culture, and the receptor was purified bound to
      either aldosterone or cortisol. Recombinant hMR had a molecular weight of 110
      130kDa, bound an MR DNA response element in vitro and interacted with a known co
      regulator, PGC-1alpha, in GST pull-down assays, indicating its functional
      activity. Availability of this reagent will now enable analysis of MR structure
      and ligand interactions in the context of the full-length receptor, a
      prerequisite for future development of ligand-selective MR antagonists for the
      treatment of cardiovascular disease.

PMID- 19114087
TI  - Suspended moxibustion relieves chronic visceral hyperalgesia via serotonin
      pathway in the colon.
AB  - Experiments in rats have shown that chronic visceral hyperalgesia can be relieved
      by electro-acupuncture, but the efficacy of suspended moxibustion for relieving
      chronic visceral hyperalgesia is still unclear. The present study aimed to
      evaluate the effect of suspended moxibustion on rectal sensory thresholds and to
      analyze its possible mechanisms when treating chronic visceral hypersensitivity
      rats. Suspended moxibustion was administered once daily to 37-day-old chronic
      visceral hypersensitivity rats for 7 days. The two acupoints (ST25, bilateral)
      were simultaneously given suspended moxibustion. Each treatment lasted for 15
      min. Rats in treatment of suspended moxibustion was not anesthetized. Untreated
      chronic visceral hypersensitivity rats and normal rats were used as controls. The
      abdominal withdrawal reflex was determined during 30-90 min after the first
      treatment. A 5-cm long segment of distal colon was harvested after seven
      treatments and 5-hydroxytryptamine concentrations in the colon were assayed by
      enzyme-linked immunosorbent assay. Abdominal withdrawal reflex scores from the
      rectus abdominis in response to colorectal distention were increased in rats with
      chronic visceral hypersensitivity, and the stimulation at strength of 20 mmHg was
      significantly depressed by suspended moxibustion. Suspended moxibustion increased
      the pain threshold and restored normal sensitivity by reducing 5
      hydroxytryptamine concentrations in the colon of chronic visceral
      hypersensitivity rats.

PMID- 19114088
TI  - gamma-Secretase activity modulates store-operated Ca2+ entry into rat sensory
      neurons.
AB  - Presenilin-1 is required for gamma-secretase activity, which participates in
      Notch receptor processing, the pathogenesis of Alzheimer's disease and the
      modulation of Ca(2+) signaling. We tested the hypothesis that gamma-secretase
      proteolytic activity modulates store-operated Ca(2+) entry (SOCE) in rat dorsal
      root ganglion (DRG) neurons. Depletion of intracellular Ca(2+) stores by blocking
      the endoplasmic reticulum (ER) Ca(2+) pump with cyclopiazonic acid (CPA) evoked a
      transient increase in [Ca(2+)](i) but no sustained Ca(2+) influx. However, in
      cells expressing a dominant negative presenilin-1 mutant (PS1-D257A), gamma
      secretase activity was inhibited and treatment with CPA evoked sustained Ca(2+)
      influx. Similarly, pharmacologic inhibition of gamma-secretase with DAPT for 48h
      enhanced SOCE. SKF96365, an inhibitor of store-operated channels, blocked SOCE in
      cells expressing PS1-D257A. Thus, gamma-secretase proteolytic activity regulates
      a SOCE pathway in sensory neurons.

PMID- 19114089
TI  - Attenuation of opioid analgesic tolerance in p75 neurotrophin receptor null
      mutant mice.
AB  - Repeated exposure to opioid drugs can lead to the development of tolerance, which
      manifests as a reduction in analgesic potency, and physical dependence, a
      response indicated by a withdrawal syndrome. Accumulating evidence suggests that
      the nerve growth factor (NGF) family of neurotrophins may have an important
      modulatory role in the induction of opioid analgesia and opioid addiction.
      Because neurotrophins universally bind the p75 neurotrophin receptor (p75NTR), we
      investigated whether the activity of this receptor is involved in the development
      of opioid analgesic tolerance and physical dependence. We found that in both the
      wild-type and p75NTR-/- mice an acute systemic (i.p.) injection of morphine
      produced a maximal analgesic response as measured by the thermal tail-immersion
      test. Repeated injection of morphine over 5 days in wild-type mice resulted in a
      progressive decline of the analgesic effect and a concomitant loss of the agonist
      potency, reflecting development of morphine tolerance. However, the loss of
      morphine analgesia was not observed in p75NTR-/- mice. In the second part of this
      study, mice were given escalating doses of systemic (i.p.) morphine over 5 days
      and subsequently challenged with the opioid receptor antagonist naloxone. This
      challenge precipitated a robust withdrawal syndrome that was comparable in wild
      type mice and p75NTR-/- mice. The findings suggest that p75NTR activity plays a
      critical role in the development of opioid analgesic tolerance but not in the
      induction or the expression of opioid physical dependence.

PMID- 19114091
TI  - Genotoxicity of nanomaterials: DNA damage and micronuclei induced by carbon
      nanotubes and graphite nanofibres in human bronchial epithelial cells in vitro.
AB  - Despite the increasing industrial use of different nanomaterials, data on their
      genotoxicity are scant. In the present study, we examined the potential genotoxic
      effects of carbon nanotubes (CNTs; >50% single-walled, approximately 40% other
      CNTs; 1.1 nm x 0.5-100 microm; Sigma-Aldrich) and graphite nanofibres (GNFs; 95%;
      outer diameter 80-200 nm, inner diameter 30-50 nm, length 5-20 microm; Sigma
      Aldrich) in vitro. Genotoxicity was assessed by the single cell gel
      electrophoresis (comet) assay and the micronucleus assay (cytokinesis-block
      method) in human bronchial epithelial BEAS 2B cells cultured for 24h, 48h, or 72h
      with various doses (1-100 microg/cm(2), corresponding to 3.8-380 microg/ml) of
      the carbon nanomaterials. In the comet assay, CNTs induced a dose-dependent
      increase in DNA damage at all treatment times, with a statistically significant
      effect starting at the lowest dose tested. GNFs increased DNA damage at all doses
      in the 24-h treatment, at two doses (40 and 100 microg/cm(2)) in the 48-h
      treatment (dose-dependent effect) and at four doses (lowest 10 microg/cm(2)) in
      the 72-h treatment. In the micronucleus assay, no increase in micronucleated
      cells was observed with either of the nanomaterials after the 24-h treatment or
      with CNTs after the 72-h treatment. The 48-h treatment caused a significant
      increase in micronucleated cells at three doses (lowest 10 microg/cm(2)) of CNTs
      and at two doses (5 and 10 microg/cm(2)) of GNFs. The 72-h treatment with GNFs
      increased micronucleated cells at four doses (lowest 10 microg/cm(2)). No dose
      dependent effects were seen in the micronucleus assay. The presence of carbon
      nanomaterial on the microscopic slides disturbed the micronucleus analysis and
      made it impossible at levels higher than 20 microg/cm(2) of GNFs in the 24-h and
      48-h treatments. In conclusion, our results suggest that both CNTs and GNFs are
      genotoxic in human bronchial epithelial BEAS 2B cells in vitro. This activity may
      be due to the fibrous nature of these carbon nanomaterials with a possible
      contribution by catalyst metals present in the materials-Co and Mo in CNTs
      (<5wt.%) and Fe (<3wt.%) in GNFs.

PMID- 19114090
TI  - Anxiety-like behaviors in mice lacking GIT2.
AB  - G protein-coupled receptor kinase-interactor 2 (GIT2) is a signaling scaffold
      protein that also functions as GTPase-activating protein (GAPs) for ADP
      ribosylation factor (Arf) small GTP-binding proteins. GIT2 has been implicated in
      the regulation of G protein-coupled receptor trafficking and cell adhesion and
      migration. To evaluate possible neurobehavioral functions of GIT2 in vivo, we
      evaluated GIT2-knockout (KO) mice for abnormalities in emotionality and mood.
      Male and female GIT2-KO mice presented with anxiety-like behaviors in the zero
      maze and light-dark emergence tests. Immobility times in tail suspension were
      reduced in GIT2-KO males, but were normal in GIT2-KO females. Hence, GIT2-KO mice
      display anxiety-like behavior in an absence of depressive-like responses.

PMID- 19114092
TI  - Production and physico-chemical characterisation of nanoparticles.
AB  - Synthetic nanoscaled metal oxides are mainly produced by pyrogenic decomposition
      of precursors in the gas phase using a hot-wall or plasma reactor. Due to their
      low production rate and limited scalability, these processes are of minor
      technical relevance in manufacturing commercial quantities of nanoparticles. The
      most common and by far the most important industrial process is flame hydrolysis.
      In this process, a gaseous mixture of a metal chloride precursor, hydrogen and
      air is introduced in a closed and continuously operated flame reactor. The
      general mechanism of formation and growth of particles (e.g. silica) occurring in
      the flame is dominated by nucleation, coalescence (sintering) and coagulation
      (collision) of primary particles forming aggregated structures. The term
      'aggregate' describes clusters of particles held together by strong chemical
      bonds. Agglomerates, however, are defined as loose accumulations of particles
      held together by hydrogen bonds for example. Although, a variety of physico
      chemical methods exist to characterise pyrogenic oxides, the most important ones
      are analysis of the specific surface area by the so-called BET method,
      determination of the aggregate size by transmission electron microscopy (TEM) and
      characterisation of the phase composition by means of X-ray analysis.

PMID- 19114093
TI  - Comparing fate and effects of three particles of different surface properties:
      nano-TiO(2), pigmentary TiO(2) and quartz.
AB  - The fate of nano-TiO(2) particles in the body was investigated after inhalation
      exposure or intravenous (i.v.) injection, and compared with pigmentary TiO(2) and
      quartz. For this purpose, a 5-day inhalation study (6h/day, head/nose exposure)
      was carried out in male Wistar rats using nano-TiO(2) (100mg/m(3)), pigmentary
      TiO(2) (250mg/m(3)) and quartz dust DQ 12 (100mg/m(3)). Deposition in the lung
      and tissue distribution was evaluated, and histological examination of the
      respiratory tract was performed upon termination of exposure, and 2 weeks after
      the last exposure. Broncho-alveolar lavage (BAL) was carried out 3 and 14 days
      after the last exposure. Rats were also injected with a single intravenous dose
      of a suspension of TiO(2) in serum (5mg/kg body weight), and tissue content of
      TiO(2) was determined 1, 14 and 28 days later. The majority of the inhaled nano
      TiO(2) was deposited in the lung. Translocation to the mediastinal lymph nodes
      was also noted, although to smaller amounts than following inhalation of
      pigmentary TiO(2), but much higher amounts than after exposure to quartz.
      Systemically available nano-TiO(2), as simulated by the i.v. injection, was
      trapped mainly in the liver and spleen. The (agglomerate) particle size of lung
      deposited nano-TiO(2) was virtually the same as in the test atmosphere. Changes
      in BAL fluid composition and histological examination indicated mild neutrophilic
      inflammation and activation of macrophages in the lung. The effects were
      reversible for nano- and pigmentary TiO(2), but progressive for quartz. The
      effects observed after 5-day inhalation exposure to nano-TiO(2) were
      qualitatively similar to those reported in sub-chronic studies.

PMID- 19114094
TI  - Preparation, pharmacokinetics and tissue distribution of micelles made of reverse
      thermo-responsive polymers.
AB  - New reverse thermo-responsive polymers, poly(ethylene oxide)-poly(propylene
      oxide) multiblock copolymers (poly(ether-carbonate)s) were synthesized. The
      micelles made of new reverse thermo-responsive polymers were also prepared loaded
      with the poorly soluble anticancer drug, hydroxycamptothecin (HCPT). The
      structure characterization of poly(ether-carbonate)s was determined by (1)H NMR
      and FT-IR analysis. The critical micelle concentration (CMC), critical micelle
      temperature (CMT), size distribution and drug release in vitro were determined.
      The pharmacokinetics and tissue distribution in vivo for novel copolymer micelles
      were studied. The experimental results showed that the micelles was spherical in
      appearance and dispersed well. The process of HCPT release from micelles in vitro
      was composed of two steps, abrupt release and sustained release. After i.v.
      administration (2h), the drug concentration of poly(ether-carbonate) micelles
      group in liver in mice was 3.46microg/g, while that of HCPT injection group was
      0.401microg/g. Compared with HCPT injection, the elimination half-life of
      poly(ether-carbonate) micelles group was prolonged remarkably from 1.3 to 12.5h.
      The poly(ether-carbonate) micelles showed a combination of liver targeting and
      sustained drug release in experiments on animals.

PMID- 19114095
TI  - Targeted delivery of methotrexate to skeletal muscular tissue by thermosensitive
      magnetoliposomes.
AB  - Thermosensitive magnetoliposomes (TMs) encapsulated with methotrexate (MTX) were
      prepared with 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC) and cholesterol
      by reverse-phase evaporation. Encapsulation efficiency of MTX and hydrophilic
      magnetite Fe(2)O(3)-glu, liposome particle size, zeta-potential, and in vitro and
      in vivo drug release were studied. More than 80% of loaded MTX was released from
      TMs within 30min when the environmental temperature increased from 37 degrees C
      to 41 degrees C, while 60% of the drug was remained inside TMs for up to 24h at
      37 degrees C. Furthermore, the pharmacokinetics and tissue distribution study
      showed that TMs significantly increased the accumulation of MTX in the skeletal
      muscular tissue when exposed to an external constant magnetic field and heated to
      41 degrees C compared to the absence of the magnetic field and heating.
      Therefore, the results in this study suggested that TMs prepared by reverse-phase
      evaporation can archive a good magnetic targeting effect and fast drug release in
      response to hyperthermia, which implies their great potential of application in
      cancer therapy.

PMID- 19114096
TI  - Scintigraphic evaluation of colon targeting pectin-HPMC tablets in healthy
      volunteers.
AB  - The in vivo evaluation of colon-targeting tablets was conducted in six healthy
      male volunteers. A pectin-hydroxypropyl methylcellulose coating was compressed
      onto core tablets labelled with 4MBq (99m)Tc-DTPA. The tablets released in the
      colon in all subjects; three in the ascending colon (AC) and three in the
      transverse colon (TC). Tablets that released in the TC had reached the AC before
      or just after food (Group A). The other three tablets released immediately upon
      AC entry at least 1.5h post-meal (Group B). Release onset for Group B was earlier
      than Group A (343min vs 448min). Group B tablets exhibited a clear residence
      period at the ileocaecal junction (ICJ) which was not observed in Group A.
      Prolonged residence at the ICJ is assumed to have increased hydration of the
      hydrogel layer surrounding the core tablet. Forces applied as the tablets
      progressed through the ICJ may have disrupted the hydrogel layer sufficiently to
      initiate radiolabel release. Conversely, Group A tablets moved rapidly through
      the AC to the TC, possibly minimising contact times with water pockets.
      Inadequate prior hydration of the hydrogel layer preventing access of
      pectinolytic enzymes and reduced fluid availability in the TC may have retarded
      tablet disintegration and radiolabel diffusion.

PMID- 19114097
TI  - Development of an oral rutin nanocrystal formulation.
AB  - Dried rutin nanocrystals have been prepared by lyophilization and investigated
      regarding their physicochemical properties with respect to re-dispersability,
      particle size, morphology and dissolution behavior. Photon correlation
      spectroscopy (PCS) and laser diffractometry (LD) were employed to determine the
      particle size. Morphology of the particles was analyzed by light microscopy.
      Lyophilized rutin nanocrystals were incorporated into tablets and the dissolution
      behavior of the tablets was evaluated. Very fine particles of lyophilized rutin
      could be completely re-dispersed in the water. The PCS size average and
      polydispersity index (PI) of lyophilized rutin were of 721nm and of 0.288 after
      re-dispersion. The rutin nanocrystal-loaded tablets were produced using direct
      compression. The dissolution velocity of the rutin nanocrystal-loaded tablet was
      superior compared to rutin microcrystal-loaded and a marketed tablet. After 30min
      rutin was released and dissolved completely from the nanocrystal tablets in
      water. In contrast, only 71% and 55% of the total amount of rutin were dissolved
      from the microcrystal tablets and the marketed tablet, respectively. The
      improving dissolution behavior of the rutin nanocrystal-loaded tablet should lead
      to a better bioavailability of the poorly soluble rutin in the body.

PMID- 19114098
TI  - In vitro and ex vivo bioadhesivity analysis of polymeric intravaginal caplets
      using physicomechanics and computational structural modeling.
AB  - The in vitro and ex vivo bioadhesivity of polyacrylic acid (PAA)-based
      intravaginal caplets was explored from a physicomechanical and chemometrical
      structural modeling viewpoint. An Extreme Vertices Mixture Design was constructed
      for analyzing the bioadhesivity of 11 matrices that were optimized. Two sets of
      crosslinked PAA-based matrices comprising either allyl-sucrose (AS-PAA) or allyl
      penta-erythritol (APE-PAA) were explored. Powders were compressed into caplet
      shaped matrices and rotational rheological analysis was performed on hydrated
      polymeric blends. Caplets were evaluated for bioadhesiveness using a simulated
      vaginal membrane (SVM) with optimized caplets further tested using freshly
      excised rabbit vaginal tissue. The SVM and caplets were hydrated in simulated
      vaginal fluid before bioadhesivity testing using a texture analyzer to determine
      the rupture force between the membranous substrates and hydrated caplets.
      Computational and molecular structural modeling deduced transient sol-gel
      mechanisms, chemical interactions and inter-polymeric interfacing during caplet
      substrate bioadhesion. Peak adhesive force (PAF) and work of adhesion (AUC(FD))
      values for the APE-PAA caplets (1.671+/-0.232N; 0.0010+/-0.0002J) were higher
      than the AS-PAA caplets (1.168+/-0.093N; 0.00030+/-0.0001J) revealing superior
      bioadhesiveness. Similarly, rheological analysis revealed APE-PAA blends with
      higher viscosity and shear stress values (9x10(5)mPa/180Pa). The optimized APE
      PAA matrices adhered appreciably to rabbit vaginal tissue (PAF=0.883+/-0.083N;
      AUC(FD)=(0.0003+/-3.5355)x10(-5)J). Results strongly suggest that the approach
      may be useful for assessing the bioadhesivity of intravaginal matrices on ex vivo
      rabbit vaginal tissue with data further supported by molecular structural
      analysis and energy-dependant bioadhesivity modeling.

PMID- 19114099
TI  - Design and in vivo evaluation of an indapamide transdermal patch.
AB  - The aim of the present study was to develop and evaluate a novel drug-in-adhesive
      transdermal patch system for indapamide. Initial in vitro experiments were
      conducted to optimize formulation parameters prior to transdermal delivery in
      rats. The effects of the type of adhesive and the content of permeation enhancers
      on indapamide transport across excised rat skin were evaluated. The results
      indicated that DURO-TAK adhesive 87-2852 is a suitable and compatible polymer for
      the development of transdermal drug delivery systems for indapamide. The final
      formulation contained 4% N-dodecylazepan-2-one, 6% l-menthol and 3% isopropyl
      myristate. For in vivo studies patch systems were administered transdermally to
      rats while orally administered indapamide in suspension was used as a control.
      The PK parameters, such as the maximum blood concentration (C(max)), time to
      reach the peak blood concentration (T(max)), mean residence time (MRT), area
      under the curve (AUC(0-t)) and terminal elimination half-life (T(1/2)) were
      significantly (p<0.05) different following transdermal administration compared
      with oral administration. In contrast to oral delivery, a sustained activity was
      observed over a period of 48h after transdermal administration. This sustained
      activity was due to the controlled release of drug into the systemic circulation
      following transdermal administration.

PMID- 19114100
TI  - Effects of sex, gonadal hormones, and augmented acoustic environments on
      sensorineural hearing loss and the central auditory system: insights from
      research on C57BL/6J mice.
AB  - Mice of the C57BL/6J (B6) inbred strain exhibit genetic progressive sensorineural
      hearing loss and have been widely used as a model of adult-onset hearing loss and
      presbycusis. Males and females exhibit similar degrees of hearing loss until
      about 3 months of age, after which, the loss accelerates in females. This paper
      reviews research on how the B6 auditory system is affected by sex, gonadectomy
      (i.e., a reduction of gonadal hormone levels), and nightly exposure to moderately
      intense augmented acoustic environments (AAEs) - a low-frequency noise band
      (LAAE) or high-frequency band (HAAE). Several findings indicate a negative effect
      of ovarian hormones on the female B6 auditory system. Whereas the sex difference
      in high-frequency hearing loss was not significantly affected by gondadectomies,
      the female disadvantage in ABR thresholds at lower frequencies was erased by
      ovariectomy. Moreover, exposure to the LAAE or HAAE caused losses of hair cells
      that were more severe in intact females than in ovariectomized females or in
      males. Finally, intact females had more severe loss of neurons in the low
      frequency region of the anterior ventral cochlear nucleus (AVCN) than other
      groups. In contrast, the presence of androgens had beneficial effects. Loss of
      hair cells and AVCN neurons after AAE exposure were more severe in
      orchidectomized males than in intact males. Ideas, hypotheses, and potential
      mechanisms concerning the findings are discussed.

PMID- 19114101
TI  - Reduced proliferative activity of primary POMGnT1-null myoblasts in vitro.
AB  - Protein O-linked mannose beta1,2-N-acetylglucosaminyltransferase 1 (POMGnT1) is
      an enzyme that transfers N-acetylglucosamine to O-mannose of glycoproteins.
      Mutations of the POMGnT1 gene cause muscle-eye-brain (MEB) disease. To obtain a
      better understanding of the pathogenesis of MEB disease, we mutated the POMGnT1
      gene in mice using a targeting technique. The mutant muscle showed aberrant
      glycosylation of alpha-DG, and alpha-DG from mutant muscle failed to bind laminin
      in a binding assay. POMGnT1(-/-) muscle showed minimal pathological changes with
      very low-serum creatine kinase levels, and had normally formed muscle basal
      lamina, but showed reduced muscle mass, reduced numbers of muscle fibers, and
      impaired muscle regeneration. Importantly, POMGnT1(-/-) satellite cells
      proliferated slowly, but efficiently differentiated into multinuclear myotubes in
      vitro. Transfer of a retrovirus vector-mediated POMGnT1 gene into POMGnT1(-/-)
      myoblasts completely restored the glycosylation of alpha-DG, but proliferation of
      the cells was not improved. Our results suggest that proper glycosylation of
      alpha-DG is important for maintenance of the proliferative activity of satellite
      cells in vivo.

PMID- 19114102
TI  - Spitzenkorper, vacuoles, ring-like structures, and mitochondria of Phanerochaete
      velutina hyphal tips visualized with carboxy-DFFDA, CMAC and DiOC6(3).
AB  - Growth and organelle morphology in the wood rotting basidiomycete fungus
      Phanerochaete velutina were examined in Petri dishes, on agar-coated slides, and
      in submerged cultures, using DIC, fluorescence and four-dimensional (4-D;
      x,y,z,t) confocal microscopy, with several fluorescent probes. Phanerochaete is
      ideal for this work because of its fast growth, robustness, and use in a wide
      range of other studies. The probe carboxy-DFFDA, widely used for labelling
      vacuoles, has no effect either on hyphal tip extension or colony growth at the
      concentrations usually applied in labelling experiments. Carboxy-DFFDA labels the
      vacuoles and these form a tubular reticulum in hyphal tip cells. The probe also
      labels extremely small vesicles (punctate fluorescence) in the apex of tip cells,
      the Spitzenkorper, and short tubules that undergo sequences of characteristic
      movements and transformations to produce various morphologies, including ring
      like structures. Their location and behaviour suggest that they are a distinct
      group of structures, possibly a subset of vacuoles, but as yet to be fully
      identified. Regular incursions of tubules extending from these structures and
      from the vacuolar reticulum into the apical dome indicate the potential for
      delivery of material to the apex via tubules as well as vesicles. Such structures
      are potential candidates for delivering chitin synthases to the apex.
      Spitzenkorper behaviour has been followed as hyphal tips with linear growth
      encounter obstacle hyphae and, as the hydrolysis product of carboxy-DFFDA only
      accumulates in membrane-enclosed compartments, it can be inferred that the
      labelled structures represent the Spitzenkorper vesicle cloud. Mitochondria also
      form a reticular continuum of branched tubules in growing hyphal tips, and dual
      localisation with DiOC6(3) and CMAC allows this to be distinguished from the
      vacuolar reticulum. Like vacuolar tubules, mitochondrial tubules also span the
      septa, indicating that they may also be a conduit for intercellular transport.

PMID- 19114103
TI  - Variability in the cadherin gene in an Ostrinia nubilalis strain selected for
      Cry1Ab resistance.
AB  - Transgenic corn expressing Cry1Ab (a Bacillus thuringiensis toxin) is highly
      effective in the control of Ostrinia nubilalis. For its toxic action, Cry1Ab has
      to bind to specific insect midgut proteins. To date, in three Lepidoptera species
      resistance to a Cry1A toxin has been conferred by mutations in cadherin, a
      protein of the Lepidoptera midgut membrane. The implication of cadherin in the
      resistance of an Ostrinia nubilalis colony (Europe-R) selected with Bacillus
      thuringiensis Cry1Ab protoxin was investigated. Several major mutations in the
      cadherin (cdh) gene were found, which introduced premature termination codons
      and/or large deletions (ranging from 1383 to 1701bp). The contribution of these
      major mutations to the resistance was analyzed in resistant individuals that
      survived exposure to a high concentration of Cry1Ab protoxin. The results
      indicated that the presence of major mutations was drastically reduced in
      individuals that survived exposure. Previous inheritance experiments with the
      Europe-R strain indicated the involvement of more than one genetic locus and
      reduced amounts of the cadherin receptor. The results of the present work support
      a polygenic inheritance of resistance in the Europe-R strain, in which mutations
      in the cdh gene would contribute to resistance by means of an additive effect.

PMID- 19114104
TI  - A serine protease in the midgut of the silkworm, Bombyx mori: protein sequencing,
      identification of cDNA, demonstration of its synthesis as zymogen form and
      activation during midgut remodeling.
AB  - We identified a serine protease with a molecular mass of 37kDa in the midgut of
      the silkworm, Bombyx mori. The activity of this protease (37-kDa protease: p37k)
      appears after pupation, when the metamorphic remodeling of the midgut is under
      progress. The sequence analysis of the purified protease and its cDNA revealed
      that p37k is a trypsin-type serine protease, which is highly similar to serine
      proteases of other insects, including CG4386 of Drosophila melanogaster. In our
      molecular phylogenetic analysis, these proteases are grouped together with CG4386
      like serine proteases of other insects to form an isolated cluster. The p37k
      protein and its putative orthologs present in this cluster have two unique
      sequence motifs, CxxCxC and FIDWLxxLLG, in the N-terminal side of the catalytic
      region. The gene for p37k is expressed in the midgut on day 2 of the silk
      spinning larva, and the p37k polypeptide becomes detectable with a specific
      antibody at this stage of the midgut. On the other hand, p37k activity is not
      detectable until pupation, indicating that p37k is present in the larval midgut
      as an inactive precursor, which then is activated after pupation. A recombinant
      p37k produced using a baculovirus system is also inactive in its intact form.
      However, the recombinant p37k can be converted to an active protease when
      incubated in the homogenate of the midgut, suggesting that some unidentified
      midgut factor(s) are involved in the activation of p37k.

PMID- 19114105
TI  - Regulation of cancer cell metabolism by hypoxia-inducible factor 1.
AB  - The induction of hypoxia-inducible factor 1 (HIF-1) activity, either as a result
      of intratumoral hypoxia or loss-of-function mutations in the VHL gene, leads to a
      dramatic reprogramming of cancer cell metabolism involving increased glucose
      transport into the cell, increased conversion of glucose to pyruvate, and a
      concomitant decrease in mitochondrial metabolism and mitochondrial mass. Blocking
      these adaptive metabolic responses to hypoxia leads to cell death due to toxic
      levels of reactive oxygen species. Targeting HIF-1 or metabolic enzymes encoded
      by HIF-1 target genes may represent a novel therapeutic approach to cancer.

PMID- 19114106
TI  - Implementation of a flash-photolysis system for time-resolved cryo-electron
      microscopy.
AB  - We describe here the implementation of a flash-photolysis system for time
      resolved cryo-electron microscopy. A previously designed computer-controlled cryo
      plunging apparatus [White, H.D., Thirumurugan, K., Walker, M.L., Trinick, J.,
      2003. A second generation apparatus for time-resolved electron cryo-microscopy
      using stepper motors and electrospray. J. Struct. Biol. 144, 246-252] was used as
      a hardware platform, onto which a xenon flash lamp and liquid light pipe were
      mounted. The irradiation initiates a reaction through cleavage of the photolabile
      blocking group from a biologically active compound. The timespan between flashing
      and freezing in cryogen is on the order of milliseconds, and defines the fastest
      observable reaction. Blotting of excess fluid, which takes on the order of 1s, is
      done before irradiation and thus does not represent a rate-limiting step. A
      specimen-heating problem, identified by measurements with a thermocouple, was
      alleviated with the use of thick, aluminum-coated grids.

PMID- 19114107
TI  - Visualization of proteins in intact cells with a clonable tag for electron
      microscopy.
AB  - Identification of proteins in 3D maps of cells is a main challenge in structural
      cell biology. For light microscopy (LM) clonable reagents such as green
      fluorescent protein represented a real revolution and equivalent reagents for
      transmission electron microscopy (TEM) have been pursued for a long time. To test
      the viability of the metal-binding protein metallothionein (MT) as a tag for TEM
      in cells we have studied three MT-fusion proteins in Escherichia coli: AmiC, a
      component of the division ring, RecA, a DNA-binding protein, and a truncated
      cytoplasmic form of maltose-binding protein (MBP). Proteins fused to MT were
      expressed in E. coli. live cells treated with gold salts were processed by fast
      freezing and freeze-substitution. Small electron-dense particles were detected in
      sections of bacteria expressing the MT-fusion proteins and immunogold labelling
      confirmed that these particles were associated to the fusion proteins. The
      distribution of the particles correlated with the functional locations of these
      proteins: MBP-MT3 concentrated in the cytoplasm, AmiC-MT1 in the bacterial
      division ring and RecA-MT1 in the nucleoid. The electron-dense tag was easily
      visualized by electron tomography and in frozen-hydrated cells.

PMID- 19114108
TI  - Nucleotide dependent packing differences in helical crystals of the ABC
      transporter MsbA.
AB  - Bacterial ATP binding cassette (ABC) exporters fulfill a wide variety of
      transmembrane transport roles and are homologous to the human multidrug
      resistance P-glycoprotein. Recent X-ray structures of the exporters MsbA and
      Sav1866 have begun to describe the conformational changes that accompany the ABC
      transport cycle. Here we present cryo-electron microscopy structures of MsbA
      reconstituted into a lipid bilayer. Using ATPase inhibitors, we captured three
      nucleotide transition states of the transporter that were subsequently
      reconstituted into helical arrays. The enzyme-substrate complex (trapped by ADP
      aluminum fluoride or AMPPNP) crystallized in a different helical lattice than the
      enzyme-product complex (trapped by ADP-vanadate). Approximately 20A resolution
      maps were calculated for each state and revealed MsbA to be a dimer with a large
      channel between the membrane spanning domains, similar to the outward facing
      crystal structures of MsbA and Sav1866. This suggests that while there are likely
      structural differences between the nucleotide transition states, membrane
      embedded MsbA remains in an outward facing conformation while nucleotide is
      bound.

PMID- 19114109
TI  - Acetazolamide reversibly inhibits water conduction by aquaporin-4.
AB  - Aquaporin-4 (AQP4) has been implicated in cytotoxic brain edema resulting from
      water intoxication, brain ischemia or meningitis. AQP4 inhibitors suitable for
      clinical use would thus be expected to help protect against brain edema. Here, we
      report the effect of inhibitors on water conduction by AQP4 and AQP1
      reconstituted into liposomes. Acetazolamide (AZA), an inhibitor of sulfonamide
      carbonic anhydrase (CA), reversibly inhibits water permeation through AQP4, but
      not through AQP1. Methazolamide (MZA), another sulfonamide CA inhibitor similar
      in chemical structure to AZA, shows no significant effect on water conduction by
      AQP4 or AQP1. Our results thus demonstrate that AZA acts as a reversible
      inhibitor for AQP4-mediated water conduction and indicate that AZA is specific,
      at least to some degree, for AQP4. AZA may thus serve as a lead compound for the
      development of AQP4-specific inhibitors for clinical applications.

PMID- 19114110
TI  - Chlamydia pneumoniae induces macrophage-derived foam cell formation via PPAR
      alpha and PPAR gamma-dependent pathways.
AB  - In the presence of low density lipoprotein (LDL), Chlamydia pneumoniae induces
      macrophage-derived foam cell formation, a typical pathological feature of early
      atherosclerosis. However, its mechanism has not been fully understood. Peroxisome
      proliferator-activated receptors (PPARs) are key regulators of macrophage lipid
      metabolism. This study therefore investigated the role that PPAR alpha and PPAR
      gamma may play a role in C. pneumoniae-induced foam cell formation. Oil Red O
      staining and Lipid mass quantification showed that LDL-treated THP-1 macrophages
      infected with high doses of C. pneumoniae (5x10(5) and 1x10(6)IFU) resulted in
      the large accumulation of lipid droplets and markedly increased the ratio of
      intracellular cholesteryl ester (CE) to total cholesterol (TC) (>50%). The
      results of RT-PCR and Western blot indicated that C. pneumoniae infection dose
      dependently suppressed the expression of PPAR alpha and PPAR gamma at mRNA and
      protein levels in LDL-treated THP-1 macrophages. PPAR alpha (fenofibrate) and
      PPAR gamma (rosiglitazone) agonists, inhibited the accumulation of intracellular
      CE by C. pneumoniae in a dose-dependent manner. Furthermore, C. pneumoniae
      induced foam cell formation was significantly suppressed by higher doses of
      fenofibrate (20 and 50microM) and rosiglitazone (10 and 20microM). These results
      first reveal that C. pneumoniae induces foam cell formation via PPAR alpha and
      PPAR gamma-dependent pathway, which may contribute to its pro-atherogenic
      properties.

PMID- 19114112
TI  - The role of anaerobic bacteria in chronic suppurative otitis media in children:
      implications for medical therapy.
AB  - This review describes the microbiology, diagnosis and medical management of
      chronic suppurative otitis media (CSOM) in children highlighting the role of
      anaerobic bacteria. In studies that employed adequate method for recovery of
      anaerobic bacteria polymicrobial aerobic and anaerobic flora was isolated from
      over half of the children with CSOM. The predominant aerobic isolates were
      Staphylococcus aureus and Pseudomonas aeruginosa and the most frequently isolated
      anaerobic organisms were Peptostreptococcus, Fusobacterium spp. and pigmented
      Prevotella and Porphyromonas spp. Several studies illustrated the efficacy of
      anti-infective agents effective against anaerobic bacteria in the treatment of
      CSOM. The medical therapy of CSOM should be directed at the eradication of the
      pathogenic aerobic and anaerobic organisms.

PMID- 19114111
TI  - Phenotypic and genotypic analyses of clinical Fusobacterium nucleatum and
      Fusobacterium periodonticum isolates from the human gut.
AB  - Fusobacterium nucleatum is a Gram-negative anaerobic rod that is part of the
      normal human microflora, and has also been associated with various infections.
      Bacterial strains belonging to the species are typically heterogeneous in both
      phenotype and genotype, which can hinder their identification in a clinical
      setting. The majority of F. nucleatum isolates originate from oral sites, however
      the species is also a resident of the human gastrointestinal tract. The aim of
      this study was to compare F. nucleatum isolates from human intestinal biopsy
      samples to try and determine whether isolates from this site are divergent from
      oral isolates. We used a variety of phenotypic and genotypic markers to compare
      21 F. nucleatum and Fusobacterium periodonticum isolates from the GI tract to
      oral isolates and recognized type strains in order to study heterogeneity within
      this set. 16S rDNA and rpoB gene sequence analysis allowed us to build
      phylogenetic trees that consistently placed isolates into distinct clusters. 16S
      rDNA copy number analyses using Denaturing Gradient Gel Electrophoresis (DGGE)
      demonstrated potential for use as a method to examine clonality amongst species.
      Phenotypic analyses gave variable results that were generally unhelpful in
      distinguishing between phylogenetic clusters. Our results suggest that a) F.
      periodonticum isolates are not restricted to the oral niche; b) phenotypic
      classification is not sufficient to subspeciate isolates; c) heterogeneity within
      the species is extensive but constrained; and d) F. nucleatum isolates from the
      gut tend to identify with the animalis subspecies.

PMID- 19114113
TI  - Genotyping of Clostridium perfringens isolated from calves with neonatal
      diarrhea.
AB  - Neonatal diarrhea is one of the main causes of losses in cattle herds.
      Clostridium perfringens is a widespread enteropathogen, and is responsible for
      many animal diseases such as bovine neonatal diarrhea. Fecal samples from 141
      diarrheic calves and 129 healthy calves, aged up to 28 days and belonging to
      three herds were examined. Rates of culture positivity were 36.2% and 30.2% for
      diarrheic and nondiarrheic calves, respectively. Multiple isolates from primary
      isolation plates were subjected to simultaneous genotyping by multiplex PCR, with
      primers amplifying fragments of alpha (cpa), beta (cpb), epsilon (etx), iota
      (itxA), enterotoxin (cpe) and beta2 (cpb2) toxin-encoding genes. Only 17/51
      (33.3%) and 17/39 (43.6%) of these mixtures from diarrheic and nondiarrheic
      calves, respectively, yielded genotype information, suggesting that this may not
      be a viable approach to genotyping of isolates. Fourteen isolate mixtures from
      animals with diarrhea had only cpa (type A), one had cpa and cpb2 (type A beta2
      positive), one with cpa, itxA, and cpb2 (type E, beta2 positive), and one with
      cpa, etx, itxA, and cpb2 toxin producing strains. Among 17 isolate mixtures from
      healthy calves, 10 were exclusively type A, one was type A cpb2 positive, two
      were type E, three were type E cpb2 positive, and one was types D and E cpb2
      positive. There was no correlation between isolation of a given toxin type and
      the presence of diarrhea.

PMID- 19114114
TI  - Hypotensive effect of the nitrosyl ruthenium complex nitric oxide donor in renal
      hypertensive rats.
AB  - We have described a new compound (trans-[RuCl([15]aneN(4))NO](2+)), which in
      vitro releases NO by the action of a reducing agent such as catecholamines. We
      investigated the effect of this NO donor in lowering the mean arterial pressure
      (MAP) in severe and moderate renal hypertensive 2K-1C rats. MAP was measured
      before and after intravenous in bolus injection of the compound in conscious 2K
      1C and normotensive (2K) rats. In the hypertensive rats (basal 196.70+/-8.70mmHg,
      n=5), the MAP was reduced in -34.25+/-13.50mmHg (P<0.05) 6h after administration
      of 10mmol/L/Kg of the compound in bolus. In normotensive rats the compound had no
      effect. We have also studied the effect of the injection of 0.1mmol/L/Kg in
      normotensive (basal 118.20+/-11.25mmHg, n=4), moderate (basal 160.90+/-2.30mmHg,
      n=6), and severe hypertensive rats (basal 202.46+/-16.74 mmHg, n=6). The compound
      at the dose of 0.1mmol/L/Kg did not have effect (P>0.05) on MAP of normotensive
      and moderate hypertensive rats. However, in the severe hypertensive rats (basal
      202.46+/-16.70mmHg, n=6) there was a significant reduction on the MAP of -28.64+/
      12.45mmHg. The NO donor reduced the MAP of all hypertensive rats in the dose of
      10mmol/L/Kg and in the severe hypertensive rats at the dose of 0.1mmol/L/Kg. The
      compound was not cytotoxic to the rat aortic vascular smooth muscle cells in the
      concentration of 0.1mmol/L/Kg that produced the maximum relaxation.

PMID- 19114115
TI  - Airway smooth muscle in asthma: phenotype plasticity and function.
AB  - Clinical asthma is characterized by reversible airway obstruction which is
      commonly due to an exaggerated airway narrowing referred to as airway
      hyperresponsiveness (AHR). Although debate exists on the complex etiology of AHR,
      it is clear that airway smooth muscle (ASM) mediated airway narrowing is a major
      contributor to airway dysfunction. More importantly, it is now appreciated that
      smooth muscle is far from being a simple cell with only contractile ability
      properties. Rather, it is more versatile with the capacity to exhibit numerous
      cellular functions as it adapts to the microenvironment to which it is exposed.
      The emerging ability of individual smooth muscle cells to undergo changes in
      their phenotype (phenotype plasticity) and function (functional plasticity) in
      response to physiological and pathological cues is an important and active area
      of research. This article provides a brief review of the current knowledge and
      emerging concepts in the field of ASM phenotype and function both under healthy
      and asthmatic conditions.

PMID- 19114116
TI  - Lipid metabolites as regulators of airway smooth muscle function.
AB  - Compelling evidence identifies airway smooth muscle (ASM) not only as a target
      but also a cellular source for a diverse range of mediators underlying the
      processes of airway narrowing and airway hyperresponsiveness in diseases such as
      asthma. These include the growing family of plasma membrane phospholipid-derived
      polyunsaturated fatty acids broadly characterised by the prostaglandins,
      leukotrienes, lipoxins, isoprostanes and lysophospholipids. In this review, we
      describe the enzymatic and non-enzymatic biosynthetic pathways of these lipid
      mediators and how these are influenced by drug treatment, oxidative stress and
      airways disease. Additionally, we outline their cognate receptors, many of which
      are expressed by ASM. We describe potential deleterious and protective roles for
      these lipid mediators in airway inflammatory and remodelling processes by
      describing their effects on diverse functions of ASM in asthma that have the
      potential to contribute to asthma pathogenesis and symptoms. These functions
      include contractile tone development, cytokine and extracellular matrix
      production, and cellular proliferation and migration.

PMID- 19114117
TI  - Antitussives: the pharmacological pipeline.
AB  - The dearth of antitussives in development reflects the broad availability of over
      the-counter antitussives. However, a key finding using newly developed cough
      monitoring systems is a lack of efficacy versus placebo of currently available
      antitussives. Coupled with advances in understanding the biology of cough, this
      has created an opportunity for the development of novel, improved antitussives.
      Several pharmaceutical companies are recognizing this strategic opening and as a
      consequence are making an effort to develop heretofore seldom heard of
      "antitussive pipelines". Potential next generation antitussives may act on the
      nervous system to control an inappropriate (pathological) urge-to-cough or, in
      the case of productive cough, facilitate expectoration, thus reducing the need to
      cough.

PMID- 19114118
TI  - Up-regulation of microsomal prostaglandin E synthase-1 in COX-1 and COX-2 knock
      out mouse fibroblast cell lines.
AB  - In this paper we investigated the possible involvement of prostaglandin E
      synthases (PGESs) in compensatory mechanism. Our findings showed that microsomal
      (m)PGES-1 expression was significantly up-regulated in COX knock-out (K/O) cells
      whereas the expression of cytosolic PGES was not changed indicating that the
      induction of mPGES-1 may, at least in part, contribute to the substantial
      increase of PGE(2) production in COX K/O cell lines. The selective up-regulation
      of mPGES-1 in COX-2 K/O cells suggests that mPGES-1 may be metabolically coupled
      with COX-1 for PGE(2) formation. Addition of arachidonic acid caused significant
      induction of mPGES-1 and COX-2 in WT cells, whereas COX-1 and cPGES were not
      affected. Our earlier and the current studies demonstrate the coregulation of
      cPLA(2), COX, and mPGES-1, in PGE(2) synthesis pathway, and that these enzymes
      contribute to the elevation of PGE(2) level when one COX isoform is absent.

PMID- 19114119
TI  - Salmonella enterica Typhimurium SipA induces CXC-chemokine expression through
      p38MAPK and JUN pathways.
AB  - The role of Salmonella typhimurium type III secretion system (T3SS-1)
      translocated proteins in chemokines' expression and protein phosphorylation was
      investigated in HeLa cells. Infection of HeLa cells with S. typhimurium activated
      IL-8 and GRO-alpha expression at higher levels than infection with a S.
      typhimurium sipAsopABDE2 mutant, confirming that T3SS-1-secreted proteins are
      required to fully induce chemokine expression in HeLa cells. A S. typhimurium
      sipAsopABDE2 mutant complemented with sipA or a strain carrying a chromosomal
      copy of sipA (sopABDE2 mutant) activated chemokines at significantly higher
      levels than a S. typhimurium sipAsopABDE2 mutant. However, extracellular addition
      of recombinant SipA failed to induce IL-8 expression. Phosphorylation analyses
      revealed that S. typhimurium induced a twofold increase in the phosphorylation of
      B23, CREB1, ERK1, JUN, p38MAPK, and NR1. JUN and p38MAPK were phosphorylated by
      S. typhimurium carrying a chromosomal copy of sipA (sopABDE2 mutant) while none
      was more than twofold phosphorylated in cells infected with the S. typhimurium
      sipAsopABDE2 mutant. Treating cells with JUN and p38MAPK inhibitors significantly
      decreased IL-8 expression in sopABDE2 mutant infected cells. These data indicate
      that S. typhimurium SipA induces expression of CXC chemokines through
      phosphorylation of IL-8-transcription regulatory proteins, JUN and p38MAK.

PMID- 19114120
TI  - Mechanisms of the airway hyperresponsiveness induced by Strongyloides
      venezuelensis infection in rats: role of capsaicin-sensitive neurons.
AB  - Strongyloides venezuelensis migrates through the lungs and induces airway
      hyperresponsiveness (AHR). The present study evaluated the role of C-fibers in
      mediating airway inflammation and AHR after infection of rats with S.
      venezuelensis. Neonatal treatment with capsaicin effectively depleted sensory
      nerves. This was accompanied by inhibition of the AHR induced by S. venezuelensis
      infection. In contrast, capsaicin treatment greatly enhanced pulmonary
      inflammation, eosinophil influx and the local production of TNF-alpha. In
      conclusion, this is the first demonstration that, akin to viral and allergic AHR,
      permanent loss of sensory nerve C-fibers also reduces AHR induced by infection
      with a helminth.

PMID- 19114121
TI  - A novel dengue vaccine candidate that induces cross-neutralizing antibodies and
      memory immunity.
AB  - A novel dengue vaccine candidate comprised of a consensus dengue virus envelope
      protein domain III (cED III) was developed to fight against dengue virus
      infection. The amino acid sequence of this novel cED III was obtained by
      alignment of amino acid sequences from different isolates of the four serotypes
      of dengue viruses. A proof-of-concept study demonstrated that BALB/c mice
      immunized with the recombinant cED III developed neutralizing antibodies against
      all serotypes of dengue virus. Moreover, formulation of recombinant cED III with
      aluminum phosphate could induce long-lasting antibody responses and anamnestic
      neutralizing antibody responses following challenge with dengue virus at week 28
      after priming. These results demonstrate the possibility of developing a single
      tetravalent vaccine against dengue viral infections.

PMID- 19114122
TI  - Limited repair and structural damages displayed by skeletal muscles loaded with
      mycolactone.
AB  - Mycolactone produced by Mycobacterium ulcerans is the toxin responsible for most
      of the pathology in Buruli ulcer, the cutaneous signature of a complex disease.
      Although mycolactone cytopathicity is well described in various in vitro and in
      vivo models, the effect of this molecule on mammalian skeletal muscles has not
      been addressed. This is particularly surprising since muscle damage is
      characteristic of severe Buruli ulcer. We have thus investigated the impact of
      mycolactone on the mouse soleus muscle during degenerative and regenerative
      phases. Mice were intramuscularly injected with 300 microg of mycolactone and
      soleus muscles assessed histologically, biochemically and functionally at 7 and
      42 days post-injection. Our results show that mycolactone induces local acute and
      chronic inflammatory responses which are respectively associated with a 65% and
      68% decrease in maximal isometric force production (P(0)) relative to sham
      injections. In addition, muscle stiffness and total hydroxyproline content rose
      by 46% and 134% at day 42 relative to sham injections indicating an extensive
      fibrotic process in injured soleus muscles. Histological observations demonstrate
      significant muscle necrosis and atrophy with limited signs of regeneration.
      Together, our data indicate that mycolactone not only induces muscle damage but
      also prevents muscle regeneration to occur. These results may help to explain why
      patients with Buruli ulcer, experience muscle weakness and contracture.

PMID- 19114123
TI  - Biofilm formation on human airway epithelia by encapsulated Neisseria
      meningitidis serogroup B.
AB  - Neisseria meningitidis is the etiologic agent of meningococcal meningitis. We
      compared 48-h biofilm formation by N. meningitidis serogroup B strains NMB, MC58,
      C311 and isogenic mutants defective in capsule formation on SV-40 transformed
      human bronchial epithelial (HBE) cells in a flow cell. We demonstrated that
      strains NMB and NMB siaA-D were defective in biofilm formation over glass, and
      there was a partial rescue of biofilm growth for strain NMB on collagen-coated
      coverslips at 48 h. We demonstrated all three serogroup B strains form biofilms
      of statistically equivalent average height on HBE cells as their isogenic
      capsular mutants. Strain NMB also formed a biofilm of statistically equivalent
      biomass as the NMB siaA-D mutant on HBE cells at 6 and 48 h. These biofilms are
      significantly larger than biofilms formed over glass or collagen. Verification
      that strain NMB expressed capsule in biofilms on HBE cells was demonstrated by
      staining with 2.2.B, a monoclonal antibody with specificity for the serogroup B
      capsule. ELISA analysis demonstrated that strains MC58 and C311 also produced
      capsules during biofilm growth. These findings suggest that encapsulated
      meningococci can form biofilms on epithelial cells suggesting that biofilm
      formation may play a role in nasopharyngeal colonization.

PMID- 19114124
TI  - Leptospira interrogans requires heme oxygenase for disease pathogenesis.
AB  - We recently characterised the Leptospira interrogans heme oxygenase (hemO) gene
      and showed that HemO was required for growth with hemoglobin as the sole iron
      source. Here we investigated the role of HemO in pathogenesis. Hamsters
      inoculated with the hemO mutant showed 83% survival, compared with 33% for a
      control mutant (intergenic transposon insertion). Lung pathology was consistent
      with survival data, showing that HemO contributes significantly to pathogenesis
      and heme is a major in vivo iron source for L. interrogans. This is only the
      second defined, attenuated mutant in pathogenic Leptospira and the first to
      define function of the mutated gene.

PMID- 19114125
TI  - Therapeutic monoclonal antibodies in ophthalmology.
AB  - Monoclonal antibodies (mAbs) can be used therapeutically by binding to molecular
      targets with high specificity. Therefore, they have excellent therapeutic
      applications in ophthalmology. This manuscript presents four aspects of the
      therapeutic use of mAbs in ophthalmology: the scientific rationale, the unique
      characteristics of selected mAbs, the current state-of-the-art application, and
      relevant therapeutic mAbs for future applications in ophthalmology. We identified
      in the literature various single-agent therapies that inhibit the following
      targets: tumor necrosis factor (TNF), epithelial growth factor receptor, vascular
      endothelial growth factor (VEGF) receptor, basic fibroblast growth factor
      receptor, platelet-derived growth factor, and cluster of differentiation
      antigens. The roles of all biochemical targets in ocular diseases were evaluated.
      Current and future mAbs against various cytokines were assessed for the treatment
      of ocular diseases. The medical literature showed the clinical benefits of mAbs
      for treating angiogenic and inflammatory ocular diseases. Two anti-VEGF mAbs,
      bevacizumab and ranibizumab, and three anti-TNF agents, infliximab, etanercept,
      and adalimumab, control ocular neovascularization and intraocular inflammation.
      Other mAbs such as rituximab, daclizumab, efalizumab, and alemtuzumab showed
      positive results in animal and early clinical studies and may represent useful
      adjuvant therapies for ocular lymphoma or ocular inflammation. Ranibizumab is the
      only FDA-approved therapy; for other mAbs the so-called off-label application
      remains the standard. Intravenous administration of mAbs has demonstrated
      acceptable toxicity profiles, while intraocular injection may decrease the
      chances of systemic complications and increase the amount of drug available to
      the retina and choroid. In conclusion, effective clinical use of mAbs in
      ophthalmology is more commonly seen in the field of angiogenic vitreoretinal and
      autoimmune inflammatory diseases. The challenge for the future is combining
      biologic therapies to improve the quality and duration of responses while
      diminishing side effects. The role of mAbs within ophthalmic treatments will be
      defined according to future clinical experience and the results of randomized
      clinical trials.

PMID- 19114126
TI  - Environmental toxicity, oxidative stress and apoptosis: menage a trois.
AB  - Apoptosis is an evolutionary conserved homeostatic process involved in distinct
      physiological processes including organ and tissue morphogenesis, development and
      senescence. Its deregulation is also known to participate in the etiology of
      several human diseases including cancer, neurodegenerative and autoimmune
      disorders. Environmental stressors (cytotoxic agents, pollutants or toxicants)
      are well known to induce apoptotic cell death and to contribute to a variety of
      pathological conditions. Oxidative stress seems to be the central element in the
      regulation of the apoptotic pathways triggered by environmental stressors. In
      this work, we review the established mechanisms by which oxidative stress and
      environmental stressors regulate the apoptotic machinery with the aim to
      underscore the relevance of apoptosis as a component in environmental toxicity
      and human disease progression.

PMID- 19114127
TI  - Hepatitis C virus: a critical appraisal of approaches to therapy.

PMID- 19114128
TI  - Distinct effects of tafazzin deletion in differentiated and undifferentiated
      mitochondria.
AB  - Tafazzin is a conserved mitochondrial protein that is required to maintain normal
      content and composition of cardiolipin. We used electron tomography to
      investigate the effect of tafazzin deletion on mitochondrial structure and found
      that cellular differentiation plays a crucial role in the manifestation of
      abnormalities. This conclusion was reached by comparing differentiated
      cardiomyocytes with embryonic stem cells from mouse and by comparing different
      tissues from Drosophila melanogaster. The data suggest that tafazzin deficiency
      affects cardiolipin in all mitochondria, but significant alterations of the
      ultrastructure, such as remodeling and aggregation of inner membranes, will only
      occur after specific differentiation.

PMID- 19114130
TI  - Dyspnoea in children. Does development alter the perception of breathlessness?
AB  - Dyspnoea, the perception of an unpleasant and/or uncomfortable sensation of
      breathlessness, offers several physiological, anatomical and teleological
      analogies with pain. Pain perception has been shown to exist in the newborn,
      suggesting that dyspnoea may also occur from birth onwards. The perception of
      breathlessness will be subservient to developmental changes in the behaviour of
      sensors and lung and muscular receptors implicated in dyspnoea, some of which are
      known to be active at time of birth. For example, perinatal resetting of the
      arterial chemoreceptor could lead to transient depression of the dyspnoeic
      response to hypoxia. However, though early evoked ventilatory responses and
      peripheral receptor maturation do exist, dyspnoea will only occur if the
      corresponding central neural circuitry undergoes parallel maturation. Our
      knowledge of dyspnoea in later childhood is based on a small number of clinical
      or psychophysical studies, predominantly dealing with asthma and exercise. There
      is a thus a clear need for systematic assessment of the existence and severity of
      dyspnoea sensing in younger children that takes into account its role as an alarm
      mechanism for triggering adaptive and/or protective responses.

PMID- 19114131
TI  - Non-collision injuries in urban buses--strategies for prevention.
AB  - Public transport is a potentially important part of independent living for older
      people, but they are over-represented in non-collision bus injuries. This paper
      reports on a computational modelling approach to addressing this problem: the
      Madymo human model validated for simulating passive, seated vehicle occupants was
      adapted to simulate a standing passenger in an accelerating bus. The
      force/deformation characteristics of the bus were measured and the human model
      was expanded to include a validated active hand grip. Real world urban bus
      acceleration profiles were measured and used as inputs for the simulations.
      Balance loss could not be predicted, but injuries from contact with the vehicle
      floor following a fall were evaluated. Results show that peak bus accelerations
      measured (+/-0.32g) exceed reported acceleration thresholds for balance loss for
      a standing passenger using a handgrip (0.15g). The maximum predicted probability
      of knee and head injuries arising from impact with bus seats, handrails and walls
      were 53% and 35%, respectively. The stairwell and horizontal seatback handles
      were particularly hazardous and the latter should be replaced with vertical
      handrails. Driver training should be expanded to include video training based on
      multibody simulations to highlight the risks for standing passengers induced by
      harsh braking and acceleration.

PMID- 19114132
TI  - Impact of speed change on estimated journey time: failure of drivers to
      appreciate relevance of initial speed.
AB  - Higher speeds are associated with increases in the probability of crashing and
      the severity of the outcome. Logically drivers speed to save time, and research
      evidence supports this assertion. It is therefore important to investigate
      drivers' understanding of how speed change impacts on journey time. Since it is
      likely that drivers do not appreciate the reciprocal nature of the function which
      links these two variables, and its implications, two predictions can be made: the
      impact of a speed change will be underestimated at low speeds and overestimated
      at high speeds. This issue was addressed through four questions generated by
      manipulating Speed Change (increase versus decrease) and Starting Speed (30 mph
      versus 60 mph) with the participants being asked how they felt these variables
      would impact on journey time. These were included in a large survey addressing
      speed-related issues. Participants were a representative quota sample of 1005 UK
      drivers, interviewed by questionnaire. The findings indicated that three of the
      four questions produced results consistent with the predictions made.
      Furthermore, a repeated measures factorial ANOVA indicated that there was no real
      appreciation of how starting speed impacted on journey time. A disordinal
      interaction provided evidence that drivers wrongly believed that as starting
      speed increased the impact of a speed rise also increased; the opposite is true.
      For speed decreases, drivers appeared to think that starting speed had little
      impact on the amount of time saved. It is recommended that these findings be
      integrated into driver training and speed awareness courses.

PMID- 19114133
TI  - The influence of heavy goods vehicle traffic on accidents on different types of
      Spanish interurban roads.
AB  - This paper illustrates a methodology developed to analyze the influence of
      traffic conditions, i.e. volume and composition on accidents on different types
      of interurban roads in Spain, by applying negative binomial models. The annual
      average daily traffic was identified as the most important variable, followed by
      the percentage of heavy goods vehicles, and different covariate patterns were
      found for each road type. The analysis of hypothetical scenarios of the reduction
      of heavy goods vehicles in two of the most representative freight transportation
      corridors, combined with hypotheses of total daily traffic mean intensity
      variation, produced by the existence or absence of induced traffic gives rise to
      several scenarios. In all cases a reduction in the total number of accidents
      would occur as a result of the drop in the number of heavy goods transport
      vehicles, However the higher traffic intensity, resulting of the induction of
      other vehicular traffic, reduces the effects on the number of accidents on single
      carriageway road segments compared with high capacity roads, due to the increase
      in exposure. This type of analysis provides objective elements for evaluating
      policies that encourage modal shifts and road safety enhancements.

PMID- 19114134
TI  - The role of risk-propensity in the risky driving of younger drivers.
AB  - Young drivers are over-represented in road injury statistics, partly because they
      engage in more risky driving than older people. Although it is assumed that
      younger people have greater risk-propensity, defined as a positive attitude to
      risk, relevant theory is imprecise and relevant research is clouded by
      inappropriate measures. 89 participants aged 16-25 and 110 participants aged over
      35 were recruited outside motor registries. Participants completed a battery of
      questionnaires including Rohrmann's [Rohrmann, B. 2004. Risk attitude scales:
      concepts and questionnaires. Project report. Available at
      http://www.rohrmannresearch.net/pdfs/rohrmann-racreport.pdf (last accessed 12th
      February 2008)] measures of risk-aversion, risk-propensity, and risk-related
      motives for risky driving, as well as measures of risk-perception and risky
      driving. Compared to older drivers, younger drivers demonstrated lower risk
      aversion, and higher propensity for taking accident risks, as well as stronger
      motives for risky driving in relation to experience-seeking, excitement,
      sensation-seeking, social influence, prestige-seeking, confidence/familiarity,
      underestimation of risk, irrelevance of risk, "letting off steam", and "getting
      there quicker". Further, these variables were associated with risky driving. Some
      evidence was observed for the possibility that risk propensity moderates the
      relationship between perceived risk and risky behaviour. These results suggest
      approaches to targeting the "young driver problem".

PMID- 19114129
TI  - Recent insights into the molecular mechanisms involved in aging and the malignant
      transformation of adult stem/progenitor cells and their therapeutic implications.
AB  - Recent advancements in tissue-resident adult stem/progenitor cell research have
      revealed that enhanced telomere attrition, oxidative stress, ultraviolet
      radiation exposure and oncogenic events leading to severe DNA damages and genomic
      instability may occur in these immature and regenerative cells during
      chronological aging. Particularly, the alterations in key signaling components
      controlling their self-renewal capacity and an up-regulation of tumor suppressor
      gene products such as p16(INK4A), p19(ARF), ataxia-telangiectasia mutated (ATM)
      kinase, p53 and/or the forkhead box O (FOXOs) family of transcription factors may
      result in their dysfunctions, growth arrest and senescence or apoptotic death
      during the aging process. These molecular events may culminate in a progressive
      decline in the regenerative functions and the number of tissue-resident adult
      stem/progenitor cells, and age-related disease development. Conversely, the
      telomerase re-activation and accumulation of numerous genetic and/or epigenetic
      alterations in adult stem/progenitor cells with advancing age may result in their
      immortalization and malignant transformation into highly leukemic or tumorigenic
      cancer-initiating cells and cancer initiation. Therefore, the cell-replacement
      and gene therapies and molecular targeting of aged and dysfunctional adult
      stem/progenitor cells including their malignant counterpart, cancer-initiating
      cells, hold great promise for treating and even curing diverse devastating human
      diseases. These diseases include premature aging diseases, hematopoietic,
      cardiovascular, musculoskeletal, pulmonary, ocular, urogenital, neurodegenerative
      and skin disorders and aggressive and recurrent cancers.

PMID- 19114135
TI  - Navigational conversation impairs concurrent distance judgments.
AB  - Dual-task performance as it relates to driving, such as tuning a radio or
      manipulating a cellular phone, forces drivers to divide their attention between
      the traffic demands and the in-car task. The present study investigated how
      concurrent spatial or non-spatial cognitive distractions mediated proximity
      judgments using vehicular stimuli. Utilizing a modified version of the task
      employed by [Elias, L.J., Robinson, B. in press. Drive on the right side of the
      road: perceptual asymmetries for judgments of automobile proximity. International
      Journal of Neuroscience.] the current study examined how mental navigation
      (spatial distraction) affected accuracy and response time for depth judgments on
      vehicular stimuli in each visual field. These were compared to a control
      condition in which no distraction was present, as well as when a semantic (non
      spatial) distraction was present. We found that conversation of a navigational
      nature (i.e., spatial distraction) most negatively impacted accuracy and response
      time when processing dynamically changing vehicle proximity. Further, these
      deleterious effects appeared to be uniform throughout the visual field. Findings
      are related to driving while being distracted, with particular emphasis on the
      role of cerebral lateralization in dual-task performance.

PMID- 19114136
TI  - Risk factors for a farm vehicle public road crash.
AB  - Driver, vehicle, public road, and farm enterprise characteristics were examined
      for their combined association with farm vehicle public road crash group
      membership. North Carolina farms experiencing a public road crash from 1992 to
      2003 (n=200) were compared with a non-crash control group (n=185) for a 1:1
      case:control ratio. Five characteristics were associated with increased odds of
      crash group membership in the combined model (likelihood ratio=175.95; d.f.=15;
      p<.001): use of non-English speaking drivers (OR=3.71); use of non-family hired
      help drivers (OR=4.25); types of non-farm vehicle public road use (OR=1.39); farm
      injury history (OR=1.33); and, use of younger farm vehicle drivers (OR=1.02).
      Farms reporting older farm vehicle drivers (OR=0.97), and low farm income
      (OR=0.29) were less likely crash group members. Recommendations are discussed for
      incorporating findings into farm vehicle crash prevention research and
      interventions.

PMID- 19114137
TI  - Interactions between rail and road safety in Great Britain.
AB  - This paper discusses the results of an investigation into ways in which the
      safety risks of travel on road and rail interact with each other in Great
      Britain, other than through physical contact such as at level crossings. The two
      main foci of the paper are: (1) an analysis of the 'whole journey' risks of
      journeys for which the national rail system is the main mode, but which also
      include stages by other transport modes to provide access to the railway system;
      and (2) an analysis of the effect on safety risk of inter-modal transfers between
      rail and road. On (1), walking to and from stations was estimated to account on
      average for 65% of the overall door-to-door risk of being killed on rail
      journeys; the rail system itself accounts for 21% of the risk, and other access
      modes account for the remaining 14%. The average distance walked to and from
      stations is 0.9 km per rail journey, and this walking accounts for 5% of all
      walking nationally. On (2), it was found that increasing rail fares to fund
      railway safety measures may lead passengers to switch from rail to car, but for
      most sensible rail safety measures, the additional risks from such diversions are
      small compared with the intended rail safety benefits. However, for high-cost
      rail safety measures funded by passengers, the additional risks from diversions
      may be of the same order as the intended safety benefits. The last section of the
      paper explores the effects of variations in the casualty rates of rail users as
      pedestrians and car users, because their road risks may be different from those
      of all road users. Such variations could alter the detailed conclusions of the
      paper, but the scale of such effects appears to be modest.

PMID- 19114138
TI  - Evaluation of the Boost 'em in the Back Seat Program: using fear and efficacy to
      increase booster seat use.
AB  - OBJECTIVES: Recent research supports the use of high-threat messages when they
      are targeted appropriately and designed to promote high efficacy as well as fear.
      This research examined the effectiveness of using a novel threat-appeal approach
      to encourage parents to place their children in booster seats and rear seats of
      vehicles. METHOD: A 6-min video-intervention was created and evaluated at after
      school/daycare centers via an interrupted time series design with similar control
      sites for comparison. Caregivers (N=226) completed knowledge and practice surveys
      and fear and efficacy estimations related to childhood motor vehicle hazards.
      Researchers observed booster-seat and rear-seat use in study site parking lots.
      RESULTS: Compared to baseline and control assessments, the treatment groups'
      child passenger safety knowledge, risk-reduction attitudes, behavioral
      intentions, sense of fear related to the hazard, and sense of efficacy related to
      the recommended behaviors increased significantly. Further, observed overall
      restraint use and booster-seat use increased significantly following the
      intervention. CONCLUSIONS: Applying high-threat messages to child passenger
      safety interventions is promising and has the potential to be adapted to other
      health risk areas.

PMID- 19114139
TI  - Analytical HFACS for investigating human errors in shipping accidents.
AB  - Despite the innovative trends in marine technology and the implementation of
      safety-related regulations, shipping accidents are still a leading concern for
      global maritime interests. Ensuring the consistency of shipping accident
      investigation reports is recognized as a significant goal in order to clearly
      identify the root causes of these accidents. Hence, the goal of this paper is to
      generate an analytical Human Factors Analysis and Classification System (HFACS),
      based on a Fuzzy Analytical Hierarchy Process (FAHP), in order to identify the
      role of human errors in shipping accidents. Integration of FAHP improves the
      HFACS framework by providing an analytical foundation and group decision-making
      ability in order to ensure quantitative assessment of shipping accidents.

PMID- 19114140
TI  - Using the Attention Network Test to predict driving test scores.
AB  - Driving is a complex multi-factorial task that taps underlying mechanisms of
      cognition and attention. Not surprisingly, therefore, many tests of cognition and
      attention are significantly associated with driving outcomes. In this article, we
      introduce driving researchers and clinicians with an interest in driving to the
      Attention Network Test (ANT), which to our knowledge has not previously been used
      in driving research. It is a recently developed test that is based on a neural
      network model of the human attention system. It combines elements of Posner's
      cuing paradigm [Posner, M.I., 1980. Orienting of attention. Quarterly Journal of
      Experimental Psychology 32, 3-25.] with the Eriksen & Eriksen flanker task
      [Eriksen, B.A., Eriksen, C.W., 1974. Effects of noise letters upon the
      identification of a target letter in a nonsearch task. Perception & Psychophysics
      16, 143-149.], and provides measures of three distinct functions of attention:
      alerting, orienting, and executive function. Our results demonstrate that the ANT
      has very good concurrent validity with the Useful Field of View (UFOV), and that
      it is comparable to UFOV in its ability to predict road test scores for a
      simulated drive. These findings suggest that further investigation of the
      usefulness of the ANT as a tool for driving researchers and clinicians is
      merited.

PMID- 19114141
TI  - Misclassification of injury severity among road casualties in police reports.
AB  - This study aims to evaluate the discordance between police reports of injury
      severity among road casualties and the length of hospital stay and the Injury
      Severity Scale (ISS) by linking information from the crash records of the Hong
      Kong Police with the trauma records of a regional hospital. Sensitivity and
      specificity analyses suggest that police injury grading diverges noticeably from
      the definition of a 12-h hospital stay. Police reports overestimate injury
      severity remarkably. The results of logistic regression indicate that age, the
      ISS, and the position of the victim significantly determine the likelihood of
      police injury misclassification. Furthermore, an optimal demarcation point of the
      length of hospital stay for serious injury is estimated.

PMID- 19114142
TI  - The effects of an exercise program on several abilities associated with driving
      performance in older adults.
AB  - The purpose of this study was to investigate the effects of participation in an
      exercise program on several abilities associated with driving performance in
      older adults. Thirty-two subjects were randomly assigned to either an exercise
      group (60-81 years, n=16) or a control group (60-82 years, n=16). The exercise
      program was planned to stress perceptive, cognitive, and physical abilities. It
      lasted 12 weeks with a periodicity of three sessions of 60 min per week.
      Assessments were conducted before and after the intervention on behavioral speed
      (in single- and dual-task conditions), visual attention, psychomotor performance,
      speed perception (time-to-contact), and executive functioning. Significant
      positive effects were found at 12-week follow-up resulting from participation in
      the exercise program. Behavioral speed improvements were found in reaction time,
      movement time, and response time (both in single- and dual-task conditions);
      visual attention improvements took place in speed processing and divided
      attention; psychomotor performance improvements occurred in lower limb mobility.
      These results showed that exercise is capable of enhancing several abilities
      relevant for driving performance and safety in older adults and, therefore,
      should be promoted.

PMID- 19114143
TI  - Exploring precrash maneuvers using classification trees and random forests.
AB  - Taking evasive actions vis-a-vis critical traffic situations impending to motor
      vehicle crashes endows drivers an opportunity to avoid the crash occurrence or at
      least diminish its severity. This study explores the drivers, vehicles, and
      environments' characteristics associated with crash avoidance maneuvers (i.e.,
      evasive actions or no evasive actions). Rear-end collisions, head-on collisions,
      and angle collisions are analyzed separately using decision trees and the
      significance of the variables on the binary response variable (evasive actions or
      no evasive actions) is determined. Moreover, the random forests method is
      employed to rank the importance of the drivers/vehicles/environments
      characteristics on crash avoidance maneuvers. According to the exploratory
      analyses' results, drivers' visibility obstruction, drivers' physical impairment,
      drivers' distraction are associated with crash avoidance maneuvers in all three
      types of accidents. Moreover, speed limit is associated with rear-end collisions'
      avoidance maneuvers and vehicle type is correlated with head-on collisions and
      angle collisions' avoidance maneuvers. It is recommended that future research
      investigates further the explored trends (e.g., physically impaired drivers,
      visibility obstruction) using driving simulators which may help in legislative
      initiatives and in-vehicle technology recommendations.

PMID- 19114144
TI  - The safety of vehicles imported from right-hand-drive vehicle configuration
      countries when operated in a left-hand-drive vehicle environment.
AB  - Vehicles over 15 years of age imported into Canada are exempt from complying with
      Canadian Motor Vehicle Safety Standards (CMVSS) applicable to their years of
      production. This has led to a developing market for older imported vehicles in
      British Columbia (BC). But while mechanical inspections are carried out on such
      vehicles before they can be registered in BC, vehicles from countries that drive
      on the left side of the road (such as Japan) retain their right-hand-drive (RHD)
      control configuration. The concern with these vehicles is two-fold: first, does
      the RHD configuration lead to increased risk of crash involvement; and second,
      are these vehicles inferior in comparison to built-for-Canada vehicles of a
      similar age, with respect to occupant protection potential? In this study three
      separate methodologies were utilized in approaching these concerns: a relative
      crash culpability analysis where RHD and left-hand-drive (LHD) crash rates were
      compared for the same group of drivers; a survival analysis where time-to-first
      crash was compared between RHD and LHD drivers: and a multiple regression model
      where RHD vehicle driver risk was compared to that of a similarly constituted
      comparison group of LHD vehicle drivers. The results of all three analyses were
      consistent. RHD vehicles had a significantly greater risk of at-fault crash
      involvement over that of similar LHD vehicles. However, crashes involving RHD
      vehicles were no more severe than those involving LHD vehicles only.

PMID- 19114145
TI  - Driver-initiated distractions: examining strategic adaptation for in-vehicle task
      initiation.
AB  - Today, drivers are faced with many in-vehicle activities that are potentially
      distracting. In many cases, they are not passive recipients of these tasks;
      rather, drivers decide whether or not (or how) to perform them. In this study, we
      examined whether drivers, given knowledge of the upcoming road demands, would
      strategically delay performing in-vehicle activities until demands were reduced.
      Twenty drivers drove an instrumented van around a closed track that was divided
      into sections of varying demands and difficulty. Drivers were asked to perform
      one of four in-vehicle tasks (e.g., phone conversation; read a text message; find
      an address; pick up an object on the floor); however, they were free to decide
      when to initiate these tasks, provided they finish them before a given deadline.
      Although drivers were fully aware of the relative demands of the road, they did
      not tend to strategically postpone tasks--a finding that was consistent across
      the different tasks (p >.05). Rather, drivers tended to initiate tasks regardless
      of the current driving conditions. This strategy frequently led to driving
      errors. Given the control that drivers have over many in-vehicle distractions,
      interventions that focus on strategic decisions and planning may have merit.

PMID- 19114146
TI  - Effects of road lighting: an analysis based on Dutch accident statistics 1987
      2006.
AB  - This study estimates the safety effect of road lighting on accidents in darkness
      on Dutch roads, using data from an interactive database containing 763,000 injury
      accidents and 3.3 million property damage accidents covering the period 1987
      2006. Two estimators of effect are used, and the results are combined by applying
      techniques of meta-analysis. Injury accidents are reduced by 50%. This effect is
      larger than the effects found in most of the earlier studies. The effect on fatal
      accidents is slightly larger than the effect on injury accidents. The effect
      during twilight is about 2/3 of the effect in darkness. The effect of road
      lighting is significantly smaller during adverse weather and road surface
      conditions than during fine conditions. The effects on pedestrian, bicycle and
      moped accidents are significantly larger than the effects on automobile and
      motorcycle accidents. The risk of injury accidents was found to increase in
      darkness. The average increase in risk was estimated to 17% on lit rural roads
      and 145% on unlit rural roads. The average increase in risk during rainy
      conditions is about 50% on lit rural roads and about 190% on unlit rural roads.
      The average increase in risk with respect to pedestrian accidents is about 140%
      on lit rural roads and about 360% on unlit rural roads.

PMID- 19114147
TI  - Alcohol and drugs in fatally and non-fatally injured motor vehicle drivers in
      northern Sweden.
AB  - Alcohol and drugs are important risk factors for traffic injuries, a major health
      problem worldwide. This prospective study investigated the epidemiology and the
      presence of alcohol and drugs in fatally and hospitalized non-fatally injured
      drivers of motor vehicles in northern Sweden. During a 2-year study period, blood
      from fatally and hospitalized non-fatally injured drivers was tested for alcohol
      and drugs. The study subjects were recruited from well-defined geographical areas
      with known demographics. Autopsy reports, medical journals, police reports, and
      toxicological analyses were evaluated. Of the fatally injured, 38% tested
      positive for alcohol and of the non-fatally 21% tested positive; 7% and 13%,
      respectively, tested positive for pharmaceuticals with a warning for impaired
      driving; 9% and 4%, respectively, tested positive for illicit drugs. The most
      frequently detected pharmaceuticals were benzodiazepines, opiates, and
      antidepressants. Tetrahydrocannabinol was the most frequently detected illicit
      substance. No fatally injured women had illegal blood alcohol concentration. The
      relative proportion of positively tested drivers has increased and was higher
      than in a similar study 14 years earlier. This finding indicates that alcohol and
      drugs merit more attention in future traffic safety work.

PMID- 19114148
TI  - An area-level model of vehicle-pedestrian injury collisions with implications for
      land use and transportation planning.
AB  - There is growing awareness among urban planning, public health, and
      transportation professionals that design decisions and investments that promote
      walking can be beneficial for human and ecological health. Planners need
      practical tools to consider the impact of development on pedestrian safety, a key
      requirement for the promotion of walking. Simple bivariate models have been used
      to predict changes in vehicle-pedestrian injury collisions based on changes in
      traffic volume. We describe the development of a multivariate, area-level
      regression model of vehicle-pedestrian injury collisions based on environmental
      and population data in 176 San Francisco, California census tracts. Predictor
      variables examined included street, land use, and population characteristics,
      including commute behaviors. The final model explained approximately 72% of the
      systematic variation in census-tract vehicle-pedestrian injury collisions and
      included measures of traffic volume, arterial streets without transit, land area,
      proportion of land area zoned for neighborhood commercial and residential
      neighborhood commercial uses, employee and resident populations, proportion of
      people living in poverty and proportion aged 65 and older. We have begun to apply
      this model to predict area-level change in vehicle-pedestrian injury collisions
      associated with land use development and transportation planning decisions.

PMID- 19114149
TI  - Age-related differences in visual scanning at median-divided highway
      intersections in rural areas.
AB  - The objective of this study was to examine age-related differences in visual
      scanning as drivers performed three separate maneuvers (going straight across,
      making a left and right turn) at two median-divided highway intersections with
      different crash frequencies. An on-road study was conducted with 60 drivers in
      three age groups: younger (18-25), middle-aged (35-55), and older (65-80). The
      study consisted of two between-subject (age and gender) and two within-subject
      variables (drive maneuver and intersection type). Drivers' behavior was measured
      by the proportion of time they visually sampled towards the left, right and
      rearview mirror, and by an entropy rate representative of randomness in visual
      scanning. The results showed that older and younger drivers do not utilize their
      full scanning range when compared to middle-aged drivers, as indicated by lower
      entropy rate and the tendency to check fewer areas before executing a maneuver
      through the intersections. This trend was more obvious during left and right turn
      maneuvers indicating a greater likelihood to miss an unexpected event. Older
      drivers had a significantly smaller proportion of visual sampling to the left and
      right during intersection negotiations when compared to younger and middle-aged
      drivers. Older and younger drivers checked the rearview mirror significantly less
      when compared to middle-aged drivers.

PMID- 19114150
TI  - A note on modeling vehicle accident frequencies with random-parameters count
      models.
AB  - In recent years there have been numerous studies that have sought to understand
      the factors that determine the frequency of accidents on roadway segments over
      some period of time, using count data models and their variants (negative
      binomial and zero-inflated models). This study seeks to explore the use of random
      parameters count models as another methodological alternative in analyzing
      accident frequencies. The empirical results show that random-parameters count
      models have the potential to provide a fuller understanding of the factors
      determining accident frequencies.

PMID- 19114151
TI  - Driving while conversing: cell phones that distract and passengers who react.
AB  - The research systematically compared the driving performance and conversational
      patterns of drivers speaking with in-car passengers, hands-free cell phones, and
      remote passengers who could see the driver's current driving situation (via a
      window into a driving simulator). Driving performance suffered during cell phone
      and remote passenger conversations as compared with in-car passenger
      conversations and no-conversation controls in terms of their approach speeds,
      reaction times, and avoidance of road and traffic hazards. Of particular interest
      was the phenomenon of conversation suppression, the tendency for passengers to
      slow their rates of conversation as the driver approached a hazard. On some
      occasions these passengers also offered alerting comments, warning the driver of
      an approaching hazard. Neither conversation suppression nor alerting comments
      were present during cell phone conversations. Remote passengers displayed low
      levels of alerting comments and conversation suppression, but not enough to avoid
      negative effects on driving performance. The data suggested that conversation
      modulation was a key factor in maintaining driving performance and that seeing
      the road and traffic was not sufficient to produce it. A second experiment
      investigated whether a cell phone modified to emit warning tones could alleviate
      some of the adverse effects typically associated with cell phone conversations.
      The modified cell phone produced discourse patterns that were similar to
      passenger conversations and driving performance nearly as good as that of drivers
      who were not conversing. This latter finding supported the argument that
      conversation modulation is a key ingredient in avoiding adverse effects of
      conversations with drivers, rather than the physical presence of an in-car
      passenger.

PMID- 19114152
TI  - Benchmarking road safety: lessons to learn from a data envelopment analysis.
AB  - Road safety performance indicators (SPI) have recently been proposed as a useful
      instrument in comparing countries on the performance of different risk aspects of
      their road safety system. In this respect, SPIs should be actionable, i.e. they
      should provide clear directions for policymakers about what action is needed and
      which priorities should be set in order to improve a country's road safety level
      in the most efficient way. This paper aims at contributing to this issue by
      proposing a computational model based on data envelopment analysis (DEA). Based
      on the model output, the good and bad aspects of road safety are identified for
      each country. Moreover, targets and priorities for policy actions can be set. As
      our data set contains 21 European countries for which a separate, best possible
      model is constructed, a number of country-specific policy actions can be
      recommended. Conclusions are drawn regarding the following performance
      indicators: alcohol and drugs, speed, protective systems, vehicle, infrastructure
      and trauma management. For each country that performs relatively poor, a
      particular country will be assigned as a useful benchmark.

PMID- 19114153
TI  - The impact of a home visitation programme on household hazards associated with
      unintentional childhood injuries: a randomised controlled trial.
AB  - BACKGROUND: The continued high mortality and morbidity rates for unintentional
      childhood injuries remain a public health concern. This article reports on the
      influence of a home visitation programme (HVP) on household hazards associated
      with unintentional childhood injuries in a South African low-income setting.
      METHODS: A randomised controlled trial (n=211 households) was conducted in a
      South African informal settlement. Community members were recruited and trained
      as paraprofessional visitors. Four intervention visits were conducted over 3
      months, focusing on child development, and the prevention of burn, poison, and
      fall injuries. The HVP, a multi-component intervention, included educational
      inputs, provision of safety devices, and an implicit enforcement strategy. The
      intervention effect (IE) was measured with a standardised risk assessment index
      that compared post-intervention scores for intervention and control households.
      RESULTS: A significant reduction was observed in the hazards associated with
      electrical and paraffin appliances, as well as in hazards related to poisoning.
      Non-significant changes were observed for burn safety household practices and
      fall injury hazards. CONCLUSIONS: This study confirmed that a multi-component HVP
      effectively reduced household hazards associated with electrical and paraffin
      appliances and poisoning among children in a low-income South African setting.

PMID- 19114154
TI  - Trends in driving under the influence of drugs: a register-based study of DUID
      suspects during 1977-2007.
AB  - Our aim was to describe the incidence and trends of driving under the influence
      of drugs (DUID) and to examine the main drug findings and their trends in
      suspected DUID cases in Finland. A register-based study was conducted of all
      suspected DUID cases during 1977-2007. The data included 31,963 DUID offenders
      apprehended by the police with a positive finding for illicit/licit drug
      impairing driving performance. Toxicological results were analyzed in blood
      and/or urine specimens in one central laboratory. The incidence of suspected DUID
      cases increased 18-fold during 1977-2007. Most of the suspects were men (89.7%).
      However, the male-female ratio decreased from 13.9 to 7.3. The mean age decreased
      from 36.2 years in 1977 to 29.9 years in 2001 but has since reincreased. Most
      often found substances were benzodiazepines (75.7%), amphetamines (46.0%),
      cannabinoids (27.7%) and opioids (13.8%). Most common illicit drugs, amphetamines
      and cannabinoids, started to appear at the end of the 1980s. Poly-drug findings
      were common (77.1%). Suspected DUID cases have increased sharply after the
      introduction of a zero tolerance law, especially in regard to amphetamines. DUID
      is an increasing problem in Finland, and needs serious attention.

PMID- 19114155
TI  - The perception of causes of accidents in mountain sports: a study based on the
      experiences of victims.
AB  - Each year, accidents involving mountain sports have many repercussions, including
      alarming public opinion and society. This study outlines the results of a
      qualitative study on the responses of 135 survivors of accidents that took place
      while mountaineering, climbing, downhill skiing and ski mountaineering, hiking,
      cross-country biking, and mountain racing. A content analysis was performed on
      the textual data obtained from the responses to an online survey. The identified
      causes were: environmental events, equipment, medical events, behavioral events,
      and time pressure, but they appear combined in different ways for the analyzed
      disciplines. Results show that for downhill skiing, direct causes of accidents
      were mainly behavioral: excessive speed, skiing errors, and fatigue. For ski
      mountaineering, direct causes were errors in decision-making and skiing. In
      mountaineering, precursors were unfavorable conditions, fatigue, lack of
      preparation, and skill errors. In climbing, difficulty is an omnipresent feature,
      but the precursors are mainly errors. Our results highlight the multi-causal
      nature of accidents that take place when practicing mountain sports. Finally, we
      examine the need to promote a mountain sports culture that highlights safety and
      injury prevention.

PMID- 19114156
TI  - Correcting erroneous crash locations in transportation safety analysis.
AB  - Errors and inconsistencies in crash location records are realistic problems that
      often compromise accuracy of safety model outcomes. This paper proposes a new
      safety analysis framework where an optimal network design module that estimates
      the most-probable site for each crash is combined with the standard regression
      analysis. An effective solution algorithm based on Lagrangian relaxation is
      developed for the network design model, and an iterative computation approach is
      proposed for location estimation and statistical regression. The proposed models
      are implemented with empirical data and numerical results are presented.

PMID- 19114157
TI  - Toxic epidermal necrolysis caused by aerosolized pentamidine.

PMID- 19114158
TI  - Excessive exertion-induced elevation of N-terminal prohormone brain natriuretic
      peptide.

PMID- 19114159
TI  - Cocaine and alcohol: a potential lethal duo.

PMID- 19114160
TI  - Should a hand-carried ultrasound machine become standard equipment for every
      internist?

PMID- 19114161
TI  - Statin-induced myopathy: hypothesis about randomized evidence and clinical
      impressions.

PMID- 19114162
TI  - Asthma in seniors: Part 1. Evidence for underdiagnosis, undertreatment, and
      increasing morbidity and mortality.
AB  - At least 2 million US citizens over 65 years of age have asthma as a chronic
      disease, a number that will rapidly increase as the population ages. We used
      computer-assisted searches to identify epidemiologic studies specific for this
      age group published in the commonly available medical literature in English
      between 1988 and 2008. The prevalence of current asthma in individuals aged over
      65 years is high (5.3%). Affected patients appear to perceive symptoms of asthma
      differently than younger patients, often have comorbid conditions with similar
      symptoms, and present for medical care later and with more fixed airways
      obstruction. Approximately 50% of deaths from asthma occur in the elderly, and
      mortality is increasing (10.5/100,000). We found only one longitudinal
      epidemiologic study that addressed the natural history of asthma in patients aged
      over 65 years, and that study used historical controls. Asthma in the elderly is
      a poorly studied, growing chronic disease that is underdiagnosed and
      undertreated. Present paradigms for diagnosis require modification.

PMID- 19114163
TI  - Acute forms of tuberculosis in adults.
AB  - Although typically considered a chronic disease, tuberculosis (TB) has protean
      acute manifestations, the major forms of which are reviewed in this article. The
      pathogenesis of acute TB, although still incompletely understood, may be related
      to both epidemiologic and genetic host factors. Miliary TB manifests as a
      nonspecific clinical syndrome with a high mortality rate. The most well-known
      form of acute TB is meningitis, characterized by fever, nuchal rigidity, and a
      lymphocytic pleocytosis of the cerebrospinal fluid. Acute abdominal TB may
      present with obstruction or less commonly as perforated viscus or peritonitis.
      Critically ill patients may have acute respiratory distress syndrome, shock, or
      disseminated intravascular coagulopathy. The spectrum of disease makes diagnosis
      of acute TB difficult unless clinical suspicion of disease is high, but the high
      mortality mandates its consideration. Early initiation of therapy is crucial to
      optimize clinical outcome.

PMID- 19114164
TI  - Acute exudative tonsillitis.

PMID- 19114165
TI  - With jaundiced eyes.

PMID- 19114166
TI  - Worth a second look.

PMID- 19114167
TI  - The gardener's cellulitis.

PMID- 19114168
TI  - Disorder on the court.

PMID- 19114169
TI  - A multiplication problem.

PMID- 19114170
TI  - Hand-carried ultrasound performed by hospitalists: does it improve the cardiac
      physical examination?
AB  - OBJECTIVE: The traditional physical examination of the heart is relatively
      inaccurate. There is little information regarding whether cardiac hand-carried
      ultrasound performed by noncardiologists adds to the accuracy of physical
      examinations. The purpose of this study was to determine whether hand-carried
      ultrasound can add to the accuracy of hospitalists' cardiac physical
      examinations. METHODS: During a focused training program in hand-carried
      echocardiography, 10 hospitalists performed cardiac examinations of 354 general
      medical inpatients first by physical examination and then by hand-carried
      ultrasound. Eligible inpatients included those for whom a conventional hospital
      echocardiogram was ordered. We measured how frequently the hospitalists' cardiac
      examination with or without hand-carried ultrasound matched or came within 1
      scale level of an expert cardiologist's interpretation of the hospital
      echocardiogram. RESULTS: Adding hand-carried ultrasound to the physical
      examination improved hospitalists' assessment of left ventricular function,
      cardiomegaly, and pericardial effusion. For left ventricular function, using hand
      carried ultrasound increased the percentage of exact matches with the expert
      cardiologist's assessment from 46% to 59% (P=.005) and improved the percentage of
      within 1-level matches from 67% to 88% (P=.0001). The addition of hand-carried
      ultrasound failed to improve the assessments of aortic stenosis, aortic
      regurgitation, and mitral regurgitation. CONCLUSION: Adding hand-carried
      ultrasound to physical examination increases the accuracy of hospitalists'
      assessment of left ventricular dysfunction, cardiomegaly, and pericardial
      effusion, and fails to improve assessment of valvular heart disease. The clinical
      benefit achieved by improved immediacy of this information has not been
      determined. An important limitation is that the study assessed only 1 level of
      training in hand-carried ultrasound.

PMID- 19114171
TI  - The cost-effectiveness of hormone therapy in younger and older postmenopausal
      women.
AB  - PURPOSE: To evaluate the health and economic outcomes of hormone therapy in
      younger and older postmenopausal women. METHODS: We developed a cost
      effectiveness model to evaluate outcomes associated with hormone therapy in
      younger and older postmenopausal women, using data sources from published
      literature through March 2008. The target population was 50-year-old and 65-year
      old women given hormone therapy or no therapy, and then followed over their
      lifetime. Primary outcomes measured were quality-adjusted life-years (QALYs) and
      incremental cost per QALY gained. RESULTS: For the base-case analysis, hormone
      therapy for 15 years in the younger cohort resulted in a gain of 1.49 QALYs with
      an incremental cost of $2438 per QALY gained, compared with no therapy. The
      results for younger women were robust to all sensitivity analyses, and treatment
      remained highly cost-effective (<$10,000 per QALY gained) within the range of
      individual assumptions used. Treatment durations of 5 years and 30 years also
      were highly cost-effective. In the older cohort, treatment for 15 years resulted
      in a net gain of 0.11 QALYs with a cost of $27,953 per QALY gained. However, a
      loss of QALYs was seen in the first 9 years. The results for older women were
      sensitive to many of the assumptions used. CONCLUSIONS: Hormone therapy for 5 to
      30 years in younger postmenopausal women increases quality-adjusted life-years
      and is cost-effective. Hormone therapy started in later years results in a loss
      of quality-adjusted life for several years before a net gain can be realized.

PMID- 19114172
TI  - Long-term C-reactive protein variability and prediction of metabolic risk.
AB  - OBJECTIVE: This analysis was undertaken to determine the long-term
      intraindividual variability, determinants of change, and capacity of the
      inflammatory marker C-reactive protein (CRP) to predict metabolic traits and
      diabetes in a large community-based population. METHODS: Intraindividual CRP
      variability, predictors of CRP change, and metabolic events were evaluated in the
      Framingham Heart Study Offspring cohort using data from the same 2409
      participants with CRP measured by the same methodology at each of 3 examination
      cycles, spanning 20 years. RESULTS: Between the first and second examinations
      (averaging 16 years apart), 23% to 47% of men and 27% to 49% of women remained
      within the same quintile of CRP values. An additional 24% to 51% of men and 24%
      to 50% of women occupied an adjacent quintile. Intermediate-term CRP variability
      (over 4 years) was similar to long-term variability. Both long- and intermediate
      term variability of CRP were significantly less than that of plasma cholesterol
      measured in these same groups. Linear regression models for CRP at the
      intermediate examination demonstrated that CRP at the initial examination
      contributed the largest proportion of the variability (partial R-square = 0.27)
      seen in the overall model after adjustment for other covariates known to affect
      CRP concentrations. Although logistic regression models demonstrated that CRP
      over the intermediate term did not predict new-onset metabolic syndrome at the
      final examination, CRP did predict an increase in glucose and new-onset diabetes.
      CONCLUSION: The results of this longitudinal analysis suggest the
      intraindividual, long-term variability of CRP concentrations is relatively small
      and predictive of new diabetes over an intermediate-term of 4 years.

PMID- 19114173
TI  - The natural course of microalbuminuria among African Americans with type 2
      diabetes: a 3-year study.
AB  - BACKGROUND: The natural course of microalbuminuria in African Americans (AA) with
      type 2 diabetes is not well established. METHOD: Longitudinal analysis of 186
      African Americans with type 2 diabetes enrolled in Project Sugar, a randomized
      controlled trial of primary care-based interventions to improve diabetes control.
      RESULTS: Mean age was 59.4 years and 85% were female. Mean estimated glomerular
      filtration rate and urinary albumin-to-creatinine ratio were 75.90 mL/min/1.73
      m(2) and 1.62, respectively. Thirty-nine patients had macroalbuminuria and
      significantly higher systolic blood pressure compared with those with
      microalbuminuria (P=.01). Sixty patients had microalbuminuria, 19 progressed to
      macroalbuminuria, and none regressed. Progression was associated significantly
      with systolic blood pressure >or=115 mm Hg and requirement for blood pressure
      medication in the univariate model. In the multivariate model, the degree of
      albumin-to-creatinine ratio (odds ratio 35.51, 95% confidence interval, 2.21
      571.65) and need for blood pressure medication (odds ratio 8.96, 95% confidence
      interval, 1.35-59.70) were independently associated with progression. No
      association was observed with the use of specific antihypertensive agent.
      CONCLUSION: This study suggests that African Americans with type 2 diabetes and
      microalbuminuria experience irreversible disease that not infrequently progresses
      to overt proteinuria. The degree of microalbuminuria and blood pressure are key
      determinants in this process and should be primary targets in treating this
      population regardless of the antihypertensive class used.

PMID- 19114174
TI  - Relationship of ethnic origin, gender, and age to blood creatine kinase levels.
AB  - BACKGROUND: Creatine kinase is expressed at high levels in muscle, where it plays
      a central role in energy metabolism. Highly elevated creatine kinase levels in
      blood may indicate muscle trauma or disease. However, it is known that baseline
      creatine kinase levels are higher in African Americans than in whites and that
      they are higher in men than in women. This analysis explores the relationship of
      ethnic origin, gender, and age to baseline blood creatine kinase levels in a
      large group of adults with hypercholesterolemia. METHODS: Data from the screening
      phases of 4 North American trials of statins, which included large numbers of
      specific racial/ethnic populations, were combined for analysis. The pooled
      population (N=11,346) included 2760 African Americans, 3301 whites, 2930
      Hispanics, and 2355 South Asians. RESULTS: Creatine kinase levels varied
      according to ethnic origin, gender, and age. African American participants had
      higher median creatine kinase levels than did individuals of the 3 other
      ethnicities. Within each ethnic group, men had higher median creatine kinase
      levels than women: African Americans, 135 versus 73 U/L; whites, 64 versus 42
      U/L; Hispanics, 69 versus 48 U/L; and South Asians, 74 versus 50 U/L. An age
      dependent decrease in creatine kinase levels was noted among men, but no such
      trend was seen among women. The median creatine kinase levels for younger African
      American men exceeded the standard upper limit of normal. CONCLUSION: Physicians
      should use caution when interpreting creatine kinase levels that seem elevated,
      particularly when treating African American patients and younger men.

PMID- 19114175
TI  - Electrocardiography screening for cardiotoxicity after modified Vaccinia Ankara
      vaccination.
AB  - BACKGROUND: Symptomatic myopericarditis has been described after smallpox
      vaccination using replication-competent vaccinia strains. METHODS: We examined
      the incidence of new electrocardiogram (ECG) abnormalities and evaluated the
      safety and immunogenicity related to vaccination. Volunteer subjects (n=90) aged
      18 to 32 years were enrolled in a National Institutes of Health-sponsored phase I
      smallpox vaccination trial (Division of Microbiology and Infectious Diseases 02
      017) and observed over a 26-week period after 2 injections of IMVAMUNE, Modified
      Vaccinia Ankara vaccine (Bavarian Nordic A/S, Copenhagen, DK), followed by
      scarification with Dryvax (Wyeth Laboratories, Marietta, Penn). Diagnostic
      computer-derived ECG statements were available to the clinical study team and
      compared with those of a board-certified cardiologist who independently read the
      ECG tracings. RESULTS: Serial ECG tracings available for 89 of the subjects
      revealed new ST-segment abnormalities in 2.2% and new T-wave abnormalities in
      15.7%; the majority (71.4%) resolved on subsequent tracings. Cardiologist over
      read of computer statements resulted in frequent changes in readings,
      particularly negation of cardiac arrhythmias. A cardiology consultation was
      requested in 17 subjects for nonspecific cardiac symptoms or new abnormal ECG
      findings. Echocardiograms were performed in 12 of the 17 subjects and were normal
      except for 1 subject with possible myopericarditis after receiving Dryvax.
      CONCLUSION: New minor ECG abnormalities are common in apparently young healthy
      volunteers considered for smallpox vaccination trials. Cardiologist over-read of
      computer-generated ECG statements in vaccine trials using ECG as a screening tool
      for safety can reduce false-positive computer-determined ECG diagnoses and the
      need for inappropriate cardiology referral and additional noninvasive testing.

PMID- 19114176
TI  - Diagnosis and treatment of pheochromocytoma in an academic hospital from 1997 to
      2007.
AB  - BACKGROUND: The diagnosis and treatment of pheochromocytoma pose a challenge to
      physicians. Several trends in the presentation, diagnosis, and surgical treatment
      of pheochromocytoma have emerged in the last 10 years. The diagnostic accuracy
      and consequences of misdiagnosis of pheochromocytoma are not well known. We aimed
      to systemically study the diagnostic accuracy and treatment outcomes of
      pheochromocytoma and to reveal the causes and consequences of misdiagnosis
      (including both overdiagnosis and underdiagnosis). METHODS: We reviewed the
      electronic and paper charts of 49 patients who underwent adrenalectomy or adrenal
      biopsy with either preoperative or pathologic diagnosis of pheochromocytoma in a
      large academic hospital from 1997 to 2007. Three groups of patients
      (overdiagnosed, correctly diagnosed, and underdiagnosed) were compared on
      clinical courses, biochemical tests, imaging studies, and surgical outcomes.
      RESULTS: Pheochromocytoma was overdiagnosed in 9 patients, correctly diagnosed in
      30 patients, and underdiagnosed in 10 patients. The overdiagnosis rate was 23%
      (9/39), and the underdiagnosis rate was 25% (10/40). The 3 distinct groups of
      patients exhibited significant differences in clinical presentation, biochemical
      tests, and imaging characteristics. The most common causes of overdiagnosis were
      misinterpretation of borderline biochemical test results and overzealous imaging.
      Overdiagnosis subjected patients to unnecessary adrenalectomy and its
      complications. The most common cause of underdiagnosis was failure to consider
      and test for pheochromocytoma. Underdiagnosis resulted in dangerous adrenal
      biopsy or adrenalectomy with hypertensive crisis and nearly doubled the length of
      stay in hospital. Surgical resection of correctly diagnosed pheochromocytoma was
      largely effective and safe, but intraoperative and postoperative complications
      occurred in some patients. CONCLUSION: We conclude that misdiagnosis of
      pheochromocytoma is not uncommon and causes serious adverse effects. Correct
      interpretation of biochemical tests and imaging is crucial to a correct
      diagnosis, and pheochromocytoma should always be included in the differential
      diagnosis of any adrenal mass. Our data suggest that physician education is
      needed to improve the diagnosis and treatment of pheochromocytoma.

PMID- 19114177
TI  - Impact of shorter inpatient faculty rotations on resident learning experience.

PMID- 19114178
TI  - Norman Rockwell's humor: doctor and doll.

PMID- 19114179
TI  - The intricacies of dopamine neuron modulation.

PMID- 19114180
TI  - Update on the cardiovascular and thoracic service-line concept.

PMID- 19114181
TI  - Recognition of greatness: "the Jatene operation".

PMID- 19114182
TI  - The post-myocardial infarction scarred ventricle and congestive heart failure:
      the preeminence of magnetic resonance imaging for preoperative, intraoperative,
      and postoperative assessment.

PMID- 19114183
TI  - Five-year neurocognitive and health outcomes after the neonatal arterial switch
      operation.
AB  - OBJECTIVES: We sought to assess the 5-year neurocognition and health of an
      interprovincial inception cohort undergoing the arterial switch operation for
      transposition of the great arteries. METHODS: Sixty-nine consecutive neonates had
      operations from 1996-2003 with full-flow cardiopulmonary bypass and selective
      deep hypothermic circulatory arrest. Outcomes were recorded at 58 +/- 9 months of
      age. Univariate and multivariate analyses were used to identify outcome
      predictors, including surgical subtype and preoperative, operative, and
      postoperative variables. RESULTS: There was 1 (1.5%) operative death. Two
      children were lost to follow-up, and 1 was excluded because of postdischarge
      meningitis. Outcomes are reported for 65 survivors. Two (3%) children have
      cerebral palsy, and 7 (11%) have language disorders, 4 of whom also meet the
      criteria for autism spectrum disorder. Two of the 4 children with autism have an
      affected older sibling. Of the 61 children without autism, scores approach those
      of peers, with a full-scale intelligence quotient of 97 +/- 16, a verbal
      intelligence quotient of 97 +/- 18, a performance intelligence quotient of 96 +/-
      15, and a visual-motor integration score of 95 +/- 16. Mother's education, birth
      gestation or weight, and postoperative plasma lactate values account for 21% to
      32% of the variance of these scores. Septostomy adds 7% to the variance of visual
      motor integration scores. CONCLUSIONS: Most preschool children do well after
      surgical correction for transposition of the great arteries, including complex
      forms. Potentially modifiable variables include high preoperative plasma lactate
      levels and septostomy. A minority of children were given diagnoses of language
      disorders, including autism, in which familial factors likely contribute to
      outcome.

PMID- 19114184
TI  - A prospective observational study of human factors, adverse events, and patient
      outcomes in surgery for pediatric cardiac disease.
AB  - OBJECTIVE: To explore the impact of human factors on intraoperative adverse
      events and compensation mechanisms in pediatric cardiac surgery. METHODS:
      Prospective observations of pediatric cardiac surgical procedures were conducted.
      Patient complexity scores were calculated and outcomes recorded. The process of
      care was divided into epochs. Events were extracted and coded into compensated or
      uncompensated major and minor adverse events. Linear regression and analysis of
      variance were used to analyze the relationships between epochs, complexity,
      adverse events, and outcome. Patient-specific and procedure-specific variables
      were tested in a forward stepwise logistic regression as predictors of cases with
      1 or more major adverse events. RESULTS: One hundred two patients undergoing
      pediatric cardiac surgery were observed. An average of 1.2 (range 0-6) major
      adverse events occurred per case. The most common type of major adverse event was
      cardiovascular, and most occurred during the surgery/postbypass epoch. Cognitive
      compensation was the most common compensation mechanism for major adverse events.
      An average of 15.3 minor adverse events occurred per case. Minor adverse events
      occurred frequently during the surgery/bypass epoch and related to communication
      and coordination failures. Higher case complexity, longer surgery duration, and
      higher number of major adverse events per patient correlated with death compared
      with other outcome groups (P < .01). Case complexity (P < .01) and surgery
      duration (P < .05) were both significant predictors of major adverse events.
      CONCLUSIONS: Pediatric cardiac surgery is an ideal model to study the coordinated
      efforts of team members in a complex organizational structure. Adverse events
      occurred routinely during pediatric cardiac surgery and were mostly compensated.
      Case complexity was a significant predictor of major adverse events. The number
      of major adverse events per patient correlated with clinical outcomes.

PMID- 19114185
TI  - Borderline hypoplasia of the left ventricle in neonates: insights for decision
      making from functional assessment with magnetic resonance imaging.
AB  - OBJECTIVES: We sought to compare the usefulness of echocardiography and magnetic
      resonance imaging in neonates with a borderline small left ventricle. METHODS:
      The preoperative magnetic resonance and echocardiography studies of 20
      consecutive patients (mean age 10 +/- 9 days) undergoing magnetic resonance
      imaging were analyzed. The diagnoses were aortic stenosis (n = 3), hypoplastic
      left heart complex (n = 12), and unbalanced atrioventricular septal defect (n =
      5). The magnetic resonance imaging protocol included ventricular volumetry, flow
      measurements, and angiography. Potential left ventricular volumes, assuming an
      ideal geometric shape, were calculated by mathematically "unfolding" the
      compressed left ventricle. RESULTS: Left ventricular end-diastolic volume was
      16.0 +/- 7.0 mL/m(2) of body surface area by echocardiography and 33.5 +/- 15.5
      mL/m(2) by magnetic resonance imaging. Echocardiography consistently
      underestimated left ventricular volume and did not correlate with magnetic
      resonance. Of all echocardiographic parameters, mitral valve z-score was the best
      predictor of left ventricular end-diastolic volume by magnetic resonance (r =
      0.77; P = .02). The average potential volume increase was 8.8% for aortic
      stenosis, 35.0% for atrioventricular septal defect and 23.0% for hypoplastic left
      heart complex patients. Aortic valve diameter did not correlate with flow volume
      in the ascending aorta. Sixteen (80%) of 20 patients underwent biventricular
      repair, without early mortality. Of these, only 5 (31.3%) had a preoperative left
      ventricular end-diastolic volume of more than 20 mL/m(2) by echocardiography.
      CONCLUSIONS: Magnetic resonance imaging is feasible in neonates with borderline
      left ventricular hypoplasia. Echocardiography does not accurately measure left
      ventricular hypoplasia in these patients and may unfairly preclude some patients
      from a biventricular repair in whom magnetic resonance is reassuring.

PMID- 19114186
TI  - Coronary blood supply of the inferior wall of the right ventricle in hearts with
      Ebstein malformation: relevance to vertical plication.
AB  - OBJECTIVE: Vertical plication of the atrialized chamber in Ebstein malformation
      has been subject to debate. A major argument against it is risk of coronary
      arterial injury; however, the coronary anatomy in the malformation remains
      incompletely investigated. METHODS: We examined 17 autopsied hearts with the
      malformation. Special attention was paid to the coronary blood supply of the
      right ventricular inferior wall, focusing on the course of the posterior
      descending branch and its relationship with the interventricular septum. RESULTS:
      The right coronary artery was dominant in 11 cases (65%); the remaining 6 had
      left dominance. In 6 right-dominant hearts, the right coronary artery gave rise
      to the branch before reaching the crux of the heart. This early takeoff caused
      the entire branch to be deviated rightward. Another 2 right-dominant hearts
      showed rightward deviation of the branch course after an initial short segment
      along the septum. In contrast, in 2 left-dominant hearts, the left circumflex
      artery ran beyond the crux and then gave rise to the branch, again resulting in
      rightward deviation of the branch. These deviations allowed the branch to run on
      the thin walled part of the right ventricular inferior wall where endocardial
      stitches are placed during typical vertical plication. CONCLUSION: The posterior
      descending branch was frequently (10/17, 59%) deviated toward the right side
      relative to the interventricular septum in hearts with Ebstein malformation.
      Because of this and the thinness of the atrialized ventricular wall, care should
      be taken to the branch even with superficial endothelial stitches.

PMID- 19114187
TI  - Reconstituted fresh whole blood improves clinical outcomes compared with stored
      component blood therapy for neonates undergoing cardiopulmonary bypass for
      cardiac surgery: a randomized controlled trial.
AB  - OBJECTIVE: This study compared the effects of reconstituted fresh whole blood
      against standard blood component therapy in neonates undergoing cardiac surgery.
      METHODS: Patients less than 1 month of age were randomized to receive either
      reconstituted fresh whole blood (n = 31) or standard blood component therapy (n =
      33) to prime the bypass circuit and for transfusion during the 24 hours after
      cardiopulmonary bypass. Primary outcome was chest tube drainage; secondary
      outcomes included transfusion needs, inotrope score, ventilation time, and
      hospital length of stay. RESULTS: Patients who received reconstituted fresh whole
      blood had significantly less postoperative chest tube volume loss per kilogram of
      body weight (7.7 mL/kg vs 11.8 mL/kg; P = .03). Standard blood component therapy
      was associated with higher inotropic score (6.6 vs 3.3; P = .002), longer
      ventilation times (164 hours vs 119 hours; P = .04), as well as longer hospital
      stays (18 days vs 12 days; P = .006) than patients receiving reconstituted fresh
      whole blood. Of the different factors associated with the use of reconstituted
      fresh whole blood, lower platelet counts at 10 minutes and at the end of
      cardiopulmonary bypass, older age of cells used in the prime and throughout
      bypass, and exposures to higher number of allogeneic donors were found to be
      independent predictors of poor clinical outcomes. CONCLUSIONS: Reconstituted
      fresh whole blood used for the prime, throughout cardiopulmonary bypass, and for
      all transfusion requirements within the first 24 hours postoperatively results in
      reduced chest tube volume loss and improved clinical outcomes in neonatal
      patients undergoing cardiac surgery.

PMID- 19114188
TI  - The myocardial protective effects of a moderate-potassium adenosine-lidocaine
      cardioplegia in pediatric cardiac surgery.
AB  - OBJECTIVES: We sought to evaluate a moderate-potassium cardioplegic solution
      using adenosine and lidocaine as the arresting and protecting cardioprotective
      combination in pediatric cardiac surgery. METHODS: One hundred thirty-four
      patients with congenital heart disease were randomly allocated to one of 3 groups
      according to the cardioplegia formula used: the high-potassium (HP) group (K(+),
      20 mmol/L), 46 patients; the high-potassium adenosine-lidocaine (HPAL) group
      (K(+), 20 mmol/L; adenosine, 0.7 mmol/L; and lidocaine, 0.7 mmol/L), 44 patients;
      and the moderate-potassium adenosine-lidocaine (MPAL) group (K(+), 10 mmol/L;
      adenosine, 0.7 mmol/L; and lidocaine, 0.7 mmol/L), 44 patients. Hemodynamic data
      during the operation and postoperative data were recorded. Serum cardiac troponin
      I concentrations were examined at the time points of before cardiopulmonary
      bypass and 1, 3, 6, 12, and 24 hours after aortic crossclamp removal. RESULTS: At
      the end of cardiopulmonary bypass and modified ultrafiltration, the systolic and
      pulse pressures of the MPAL group were significantly increased compared with the
      respective values of the HP group. At the time points of 1 to 12 hours after
      reperfusion, the levels of serum cardiac troponin I were significantly decreased
      in the MPAL group compared with those in the HP and HPAL groups. CONCLUSIONS: The
      MPAL cardioplegia formula was associated with better myocardial protective
      effects.

PMID- 19114189
TI  - Formation of anti-platelet factor 4/heparin antibodies after cardiac surgery:
      influence of perioperative platelet activation, the inflammatory response, and
      histocompatibility leukocyte antigen status.
AB  - BACKGROUND: Anticoagulation therapy with heparin induces antibodies that
      recognize multimolecular complexes of platelet factor 4 bound to heparin (anti
      platelet factor 4/heparin antibodies). Considering that cardiac surgery induces
      an intense platelet activation and proinflammatory response, we examined the
      relationship between formation of anti-platelet factor 4/heparin antibodies and
      plasma levels of platelet factor 4 and interleukin 6. We also examined the
      relationship between anti-platelet factor 4/heparin seroconversion and the
      histocompatibility leukocyte antigen system. METHODS: In 71 patients undergoing
      cardiac surgery, anti-platelet factor 4/heparin antibody levels were evaluated by
      means of enzyme-linked immunosorbent assay preoperatively and 14 days
      postoperatively. Platelet serotonin release assays were performed to assess the
      platelet-activating potential of the antibodies. Plasma levels of platelet factor
      4 and interleukin 6 were assayed at prespecified time points. Histocompatibility
      leukocyte antigen status was assessed preoperatively in all patients and was
      compared with that of 6156 healthy subjects. RESULTS: Thirty-seven (52%) patients
      had anti-platelet factor 4/heparin antibodies with an OD value of 0.45 or greater
      in 1 or more of the assays. Applying strict seroconversion criteria (>2-fold
      increase in Optical Density), only 16 (22.5%) patients had evidence of anti
      platelet factor 4/heparin antibody seroconversion after the operation. Neither
      the presence of anti-platelet factor 4/heparin antibodies nor seroconversion
      influenced postoperative outcomes. The CW4 allele was significantly more frequent
      among seroconverted patients (46.9% vs 19.1%, P = .002). Platelet factor 4 levels
      did not influence seroconversion. Patients with anti-platelet factor 4/heparin
      levels of 0.45 OD units or greater 14 days after the operation had significantly
      higher interleukin 6 levels measured 1 hour after protamine administration.
      DISCUSSION: Patients with a greater amount of perioperative inflammation could be
      more likely to have anti-platelet factor 4/heparin antibodies 1 to 2 weeks later.
      We provide additional evidence that the histocompatibility leukocyte antigen CW4
      confers genetic susceptibility in an acquired inflammatory disorder that includes
      the anti-platelet factor 4/heparin immune response.

PMID- 19114190
TI  - Randomized controlled trial of a special acupuncture technique for pain after
      thoracotomy.
AB  - OBJECTIVE: We sought to determine whether an acupuncture technique specially
      developed for a surgical oncology population (intervention) reduces pain or
      analgesic use after thoracotomy compared with a sham acupuncture technique
      (control). METHODS: One hundred sixty-two patients with cancer undergoing
      thoracotomy were randomized to group A (preoperative implantation of small
      intradermal needles that were retained for 4 weeks) or group B (preoperative
      placement of sham needles at the same schedule). The numeric rating scale of pain
      and total opioid use was evaluated during the in-patient stay, and the Brief Pain
      Inventory and Medication Quantification Scale were evaluated after discharge up
      to 3 months after the operation. RESULTS: The principal analysis, a comparison of
      Brief Pain Inventory pain intensity scores at the 30-day follow-up, showed no
      significant difference between the intervention and control groups. Pain scores
      were marginally higher in the intervention group (0.05; 95% confidence interval,
      0.74 to -0.64; P = .9). There were also no statistically significant differences
      between groups for secondary end points, including chronic pain assessments at 60
      and 90 days, in-patient pain, and medication use in the hospital and after
      discharge. CONCLUSION: A special acupuncture technique, as provided in this
      study, did not reduce pain or use of pain medication after thoracotomy more than
      a sham technique.

PMID- 19114191
TI  - Acupuncture to relieve the pain of thoracotomy: commentary on randomized,
      controlled trial.

PMID- 19114192
TI  - Primary chest wall lymphoma with no history of tuberculous pyothorax: diagnosis
      and treatment.
AB  - OBJECTIVE: Primary chest wall neoplasm represents only 5% of chest wall neoplasm
      and among them primary chest wall lymphoma is uncommon. METHODS: A 28-year-old
      man had no history of tuberculous pyothorax or artificial pneumothorax therapy
      but did have a 4-month history of dyspnea, fever, chills, and night sweats. On
      physical examination, a mass about 10 x 10 cm was noted on the anterior chest
      wall on the right side, and computed tomographic scan demonstrated that it
      originated from the pleural wall. A 42-year-old man was admitted with
      intermittent left hemithoracic pain from about 6 months before his visit. A 5 x 5
      cm tender mass in the posterior wall of the left hemithorax was palpated.
      Computed tomography showed mild plural effusion and erosion in the posterior
      segment of the left ninth rib. Surgery was performed for histologic diagnosis.
      RESULTS: With the diagnosis of large B cell lymphoma, chemotherapy was prescribed
      for the first patient, and the patient has been in complete remission for more
      than 5 months. For the second patient, the left ninth rib along with the
      originated mass was completely resected and chemotherapy was prescribed. The
      patient has been in complete remission for more than 8 months. CONCLUSION:
      Treatment of primary chest wall lymphoma was not clear and various treatment
      strategies were considered. Remission of considerable duration in our patients
      leads us to suggest that surgery followed by adjuvant chemotherapy can provide a
      reasonable outcome in patients in whom the chest wall lymphoma is the only site
      of disease.

PMID- 19114193
TI  - Transverse sternal plating in secondary sternal reconstruction.
AB  - OBJECTIVES: Sternal instability after cardiac surgery occurs infrequently but can
      be challenging to manage. The most common treatment of mechanical sternal
      instability is operative rewiring. Transverse rib-to-rib stabilization with
      titanium plates designed for sternal fixation is a recent option. We evaluated
      the clinical utility of the transverse plating system in a cardiothoracic
      practice. METHODS: We retrospectively reviewed our experience with transverse
      sternal plating using the Synthes titanium sternal plate system (Synthes CMF,
      Paoli, Pa) from June 2004 to June 2007. RESULTS: There were 15 sternal
      reconstruction procedures performed in 14 patients using the transverse sternal
      plates. One patient required reoperation for sternal plate fracture. Indications
      for sternal plating were chronic sternal dehiscence in 9 procedures, acute
      sternal dehiscence in 3 procedures, previous mediastinitis and sternectomy in 2
      procedures, and sternal plate fracture in 1 procedure. The initial cardiac
      operation was isolated coronary artery bypass in all patients. The mean age was
      59 years (range, 51-68 years), all patients were men, 12 patients had a body mass
      index of greater than 30 kg/m(2) (range, 22-40 kg/m(2)), 9 patients were
      diabetic, 8 patients were active smokers, and 7 patients had chronic obstructive
      pulmonary disease. The mean follow-up period was 15.5 months (range, 3-33
      months). All patients achieved sternal stability with minimal postoperative pain.
      Complications included infection requiring explantation in 1 patient, plate
      fracture in 1 patient, and seroma formation in 1 patient. CONCLUSION: The
      transverse sternal plating system successfully achieved stability in all cases
      and is valuable in complex sternal reconstructions. Sternal plating is an
      effective alternative to wire closure in sternum with fractures, chronic and
      acute instability, or poor bone quality.

PMID- 19114194
TI  - Stage III thymoma: relationship of local invasion to recurrence.
AB  - OBJECTIVES: We investigated the relationships of recurrence site with the
      involved organ and cell type in patients with Masaoka stage III thymomas.
      METHODS: Records of 84 patients who underwent a complete resection of stage III
      thymomas between 1957 and 2005 were reviewed and then divided according to
      involved organ. The number of patients with cell types determined according to
      World Health Organization criteria were 2, 5, 7, 37, and 7 for types A, AB, B1,
      B2, and B3, respectively, whereas type was not determined in 25 patients.
      RESULTS: Lung invasion occurred in 58 patients, followed by invasion of the
      pericardium in 47 and invasion of the great vessels in 23. Recurrence occurred in
      23 patients, which included 12 with pleural dissemination and 8 with distant
      metastasis, mostly in the lung. Lung invasion was seen in 8 of the 12 patients
      with pleural recurrence, whereas vascular invasion was seen in 6 of the 8
      patients with distant metastasis. Local recurrence was less common. Disease-free
      survival after 10 years for all subjects was 74.2%, whereas it was lower for
      those with vascular invasion (46.1%) compared with those without invasion (87.1%,
      P < .05). Of the 23 patients with recurrence, World Health Organization cell
      types B1, B2, and B3 were seen in 2, 11, and 3 cases, respectively, whereas type
      was not determined in 7 patients. CONCLUSIONS: The pleural cavity and lung are
      common sites of recurrence of Masaoka stage III thymomas. It is important to
      establish an inclusive therapeutic strategy that considers the relationships of
      involved organs and sites of recurrence in these patients.

PMID- 19114195
TI  - Improvement in coronary anastomosis with cardiac surgery simulation.
AB  - OBJECTIVE: Cardiac surgery trainees might benefit from simulation training in
      coronary anastomosis and more advanced procedures. We evaluated distributed
      practice using a portable task station and experience on a beating-heart model in
      training coronary anastomosis. METHODS: Eight cardiothoracic surgery residents
      performed 2 end-to-side anastomoses with the task station, followed by 2 end-to
      side anastomoses to the left anterior descending artery by using the beating
      heart model at 70 beats/min. Residents took home the task station, recording
      practice times. At 1 week, residents performed 2 anastomoses on the task station
      and 2 anastomoses on the beating-heart model. Performances of the anastomosis
      were timed and reviewed. RESULTS: Times to completion for anastomosis on the task
      station decreased 20% after 1 week of practice (351 +/- 111 to 281 +/- 53
      seconds, P = .07), with 2 residents showing no improvement. Times to completion
      for beating-heart anastomosis decreased 15% at 1 week (426 +/- 115 to 362 +/- 94
      seconds, P = .03), with 2 residents demonstrating no improvement. Home practice
      time (90-540 minutes) did not correlate with the degree of improvement.
      Performance rating scores showed an improvement in all components. Eighty-eight
      percent of residents agreed that the task station is a good method of training,
      and 100% agreed that the beating-heart model is a good method of training.
      CONCLUSIONS: In general, distributed practice with the task station resulted in
      improvement in the ability to perform an anastomosis, as assessed by times to
      completion and performance ratings, not only with the task station but also with
      the beating-heart model. Not all residents improved, which is consistent with a
      "ceiling effect" with the simulator and a "plateau effect" with the trainee.
      Simulation can be useful in preparing residents for coronary anastomosis and can
      provide an opportunity to identify the need and methods for remediation.

PMID- 19114196
TI  - Evaluation of a novel atrial retractor for exposure of the mitral valve in a
      porcine model.
AB  - OBJECTIVES: To describe a novel atrial retractor and compare 2 methods of
      intraoperative left atrial retraction for minimally invasive mitral valve repair.
      METHODS: Left atrial retraction was performed on 5 swine cadavers to evaluate
      performance (percent of mitral valve annulus accessible), complications
      encountered, ease of use, and surgical time for the minimally invasive atrial
      retractor and a HeartPort atrial retractor. RESULTS: Estimated accessibilities
      were 93.0% (standard error = 3.2) and 92.7% (standard error = 3.3) for the
      HeartPort and minimally invasive atrial retractor retractors, respectively, with
      a difference of 0.3% (standard error = 2.2%, P = .8832, df = 34). Tissue damage
      occurred in 1 case for the minimally invasive atrial retractor and 2 cases for
      the HeartPort retractor. The mean surgical times for retractor placement and
      mitral valve annulus exposure were 107.4 and 39.2 seconds for the HeartPort and
      minimally invasive atrial retractor retractors, respectively, with a difference
      of 68.2 seconds (P = .0092, df = 4). CONCLUSIONS: The minimally invasive atrial
      retractor is a suitable alternative for atrial retraction compared with standard
      techniques of retraction. It provides comparable exposure of the mitral valve
      annulus, is less time consuming to place, provides subjectively more working
      volume within the left atrium, and has the advantage of minimal atriotomy
      incision length and customizable retraction.

PMID- 19114197
TI  - Feasibility of a three-axis epicardial accelerometer in detecting myocardial
      ischemia in cardiac surgical patients.
AB  - OBJECTIVE: We investigated the feasibility of continuous detection of myocardial
      ischemia during cardiac surgery with a 3-axis accelerometer. METHODS: Ten
      patients with significant left anterior descending coronary artery stenosis
      underwent off-pump coronary artery bypass grafting. A 3-axis accelerometer (11 x
      14 x 5 mm) was sutured onto the left anterior descending coronary artery-perfused
      region of left ventricle. Twenty episodes of ischemia were studied, with 3-minute
      occlusion of left anterior descending coronary artery at start of surgery and 3
      minute occlusion of left internal thoracic artery at end of surgery.
      Longitudinal, circumferential, and radial accelerations were continuously
      measured, with epicardial velocities calculated from the signals. During
      occlusion, accelerometer velocities were compared with anterior left ventricular
      longitudinal, circumferential, and radial strains obtained by echocardiography.
      Ischemia was defined by change in strain greater than 30%. RESULTS: Ischemia was
      observed echocardiographically during 7 of 10 left anterior descending coronary
      artery occlusions but not during left internal thoracic artery occlusion. During
      ischemia, there were no significant electrocardiographic or hemodynamic changes,
      whereas large and significant changes in accelerometer circumferential peak
      systolic (P < .01) and isovolumic (P < .01) velocities were observed. During 13
      occlusions, no ischemia was demonstrated by strain, nor was any change
      demonstrated by the accelerometer. A strong correlation was found between
      circumferential strain and accelerometer circumferential peak systolic velocity
      during occlusion (r = -0.76, P < .001). CONCLUSIONS: The epicardial accelerometer
      detects myocardial ischemia with great accuracy. This novel technique has
      potential to improve monitoring of myocardial ischemia during cardiac surgery.

PMID- 19114198
TI  - Mitral valve repair for advanced myxomatous degeneration with posterior
      displacement of the mitral annulus.
AB  - OBJECTIVE: This study examines the outcomes of mitral valve repair in a defined
      group of patients with mitral regurgitation caused by advanced myxomatous
      degeneration. METHODS: Advanced myxomatous degeneration of the mitral valve was
      defined as a degenerative process whereby both leaflets are voluminous and
      aneurysmal and the mitral annulus diameter exceeds 40 mm and has posterior
      displacement, as determined by means of echocardiographic analysis. Over a 16
      year period, we identified 183 patients who underwent valve repair in this
      subgroup of myxomatous degeneration. The repair consisted of relocating the
      posterior mitral annulus to the endocardium of the left ventricle at the
      atrioventricular junction, correction of leaflet prolapse, and annuloplasty.
      Analysis of perioperative variables and postoperative outcomes were undertaken.
      The mean follow-up was 5.9 +/- 4.2 years and complete. RESULTS: The patients'
      mean age was 52 years, and 118 were men. All patients had mitral regurgitation
      preoperatively. There were no early and only 8 late deaths (2 valve-related
      deaths). The survival at 10 years was 92% +/- 3%. Six patients required
      reoperation on the mitral valve, 5 for recurrent severe mitral regurgitation. The
      freedom from reoperation at 10 years was 93% +/- 3%. Six patients had severe and
      21 had moderate mitral regurgitation. The freedom from recurrent moderate or
      severe mitral regurgitation at 10 years was 80% +/- 5%. We could not identify
      independent predictors of recurrent mitral regurgitation. CONCLUSIONS: Mitral
      valve repair for advanced myxomatous degeneration on the mitral valve provides
      excellent early functional results, but late recurrent regurgitation is common,
      despite correction of dilated and displaced mitral annulus and leaflet prolapse.

PMID- 19114199
TI  - Effect of preoperative statins in patients without coronary artery disease who
      undergo cardiac surgery.
AB  - OBJECTIVE: 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors (statins)
      have been shown to have pleiotropic effects in addition to their lipid-lowering
      properties. Some studies have shown the beneficial effect of preoperative statins
      on operative outcomes in coronary artery bypass grafting. However, the effect of
      preoperative statins in patients without coronary artery disease who undergo
      cardiac surgery remains poorly defined. METHODS: We performed a retrospective
      review of 1389 consecutive patients undergoing cardiac valve surgery between
      January of 2002 and December of 2005. Patients undergoing concomitant coronary
      artery bypass surgery and those with a history of myocardial infarction and
      coronary interventions were excluded. Of this cohort, 363 patients were receiving
      a statin preoperatively and 1026 patients were not. Propensity scores were
      constructed with patients' demographics, clinical data, and the year of
      procedure. Generalized estimating equations, including the propensity score as a
      covariate, were used to investigate whether preoperative statin use is associated
      with improved operative outcomes. RESULTS: The crude operative mortality rate was
      0.8% and 2.3%, the incidence of stroke was 1.7% and 2.9%, and the incidence of
      perioperative myocardial infarction was 2.2% and 2.4% in the statin and non
      statin groups, respectively. Generalized estimating equations showed that
      preoperative statin use is associated with lower mortality (odds ratio: 0.25, 95%
      confidential interval: 0.12-0.54). Preoperative statin use was not significantly
      associated with an incidence of stroke (odds ratio: 0.48, 95% confidential
      interval: 0.19-1.22) or perioperative myocardial infarction (odds ratio: 0.91,
      95% confidential interval: 0.43-1.91) in this cohort. CONCLUSION: Preoperative
      use of statins may improve operative outcomes in patients without coronary artery
      disease who undergo cardiac surgery.

PMID- 19114200
TI  - Use of quantitative analysis of remote myocardial fibrosis with delayed
      enhancement magnetic resonance imaging to predict outcomes after surgical
      ventricular restoration for ischemic cardiomyopathy.
AB  - OBJECTIVE: Preserved myocardial function remote from surgical site is crucial for
      good outcome after surgical ventricular restoration in ischemic cardiomyopathy.
      We hypothesized that left ventricular scarring untouched by operation would
      negatively affect postoperative outcome. METHODS: In 15 consecutive patients
      (mean age 61 +/- 12 years, mean left ventricular ejection fraction 20% +/- 7.5%),
      left ventricular assessments by magnetic resonance imaging and right heart
      catheterization were performed before and after operation. Left ventricular basal
      scarring remote from surgical exclusion site was quantified from hyperenhancement
      area on preoperative delayed-enhancement magnetic resonance imaging as percentage
      of fibrosis (total infarct size relative to ventricular mass). RESULTS:
      Calculated percentage of fibrosis varied from 0% to 29.9% (mean 12% +/- 9.6%).
      Percentage of fibrosis linearly correlated with significantly worse postoperative
      hemodynamic variables and left ventricular function recovery: left ventricular
      ejection fraction (P = .0005, R = -0.79), left ventricular end-systolic volume
      index (P = .05, R = 0.51), mean pulmonary arterial pressure (P = .004, R = 0.70),
      pulmonary capillary wedge pressure (P = .009, R = 0.65), and cardiac index (P =
      .005, R = -0.69). At mean 30-month follow-up, 4 patients with recurrent heart
      failure had significantly greater percentage of fibrosis than did those without
      recurrence (19% +/- 8.2% vs 8.8% +/- 8.6%, P = .04). CONCLUSION: Amount of
      myocardial scarring at left ventricular base affected postoperative left
      ventricular function and hemodynamic improvements. Preoperative quantitative
      assessment of remote myocardial status with delayed-enhancement magnetic
      resonance imaging may predict outcomes for patients undergoing surgical
      ventricular restoration.

PMID- 19114201
TI  - Comparative study of single-dose and 24-hour multiple-dose antibiotic prophylaxis
      for cardiac surgery.
AB  - OBJECTIVE: Use of single-dose antibiotic prophylaxis is associated with reduced
      antibiotic resistance, lower costs, and fewer problems with drug toxicity and
      superinfections. We tested the hypothesis that single doses of cefazolin are as
      effective as a 24-hour regimen of cefazolin in preventing surgical site
      infections in adults undergoing cardiac procedures. METHODS: This random,
      prospective, clinical study included 838 adult patients undergoing elective
      coronary artery bypass grafting, valve operations, or both. These patients were
      randomly given a single dose of cefazolin (2 g) or a 24-hour treatment (2-g
      initial dose, followed by 1 g every 8 hours). Investigators blinded to the drug
      regimen diagnosed wound infections according to Centers for Disease Control and
      Prevention criteria. Patient clinical and demographic characteristics were noted,
      with follow-up for 12 postoperative months. The primary objective was to compare
      the incidence of surgical infections between groups up to 12 months
      postoperatively. RESULTS: A total of 419 patients received single-dose cefazolin,
      and another 419 received the 24-hour treatment. Surgical site infection occurred
      in 35 (8.3%) patients receiving single doses and 15 (3.6%) patients administered
      the 24-hour treatment (P = .004). We identified no differences between groups for
      mortality or duration of hospitalization (preoperative hospitalization, intensive
      care unit stay, and hospitalization after surgical intervention). The
      microorganisms isolated showed a similar distribution in both groups. The germs
      isolated were gram-positive cocci in 86% of the surgical site infections.
      CONCLUSIONS: Single-dose cefazolin used as antibiotic prophylaxis in cardiac
      surgery is associated with a higher surgical site infection rate than the 24
      hour, multiple-dose cefazolin regimen.

PMID- 19114202
TI  - The sinus of Valsalva relieves abnormal stress on aortic valve leaflets by
      facilitating smooth closure.
AB  - OBJECTIVE: Recently, various modifications have been made to aortic root
      replacement procedures to include the pseudosinus in the synthetic graft, but its
      effect on valve function still remains to be elucidated. The purpose of this
      study was to compare the flow dynamics and its influence on the stress/strain in
      the valve leaflet in two types of aortic root, either with or without the
      pseudosinus, with a simulation model. METHODS: The proximal portions of the
      ascending aorta and aortic valves were modeled with blood flowing inside. Blood
      flow and the motion of aortic valve leaflets were studied while applying a
      physiologic pressure waveform using fluid-structure interaction finite element
      analysis. Waveforms were varied to simulate the change in cardiac contractility.
      RESULTS: In the aorta without the sinus, the time during which the valve was open
      was longer and the rapid valve closing velocity was faster under all conditions
      studied. In the pseudosinus model, we could clearly observe vortex formation from
      the early phase of ejection, which seemed to facilitate the gradual but smooth
      closure of the valve. Valve leaflets without the sinus were subject to greater
      stress and underwent bending deformation in the longitudinal direction.
      CONCLUSIONS: Sinuses of Valsalva facilitate the smooth closure of the aortic
      valve, thereby avoiding the building up of abnormal stress in the leaflet. Such
      an effect may assure the durability of valve leaflets in aortic grafts with a
      pseudosinus.

PMID- 19114203
TI  - Does aortic crossclamping during the cooling phase affect the early clinical
      outcome of acute type A aortic dissection?
AB  - OBJECTIVES: The purpose of this study is to evaluate the effects of crossclamping
      the ascending aorta in acute type A aortic dissection during the cooling phase
      for deep hypothermic arrest on early clinical outcome. METHODS: The records of
      275 consecutive patients who underwent surgery for acute type A aortic dissection
      were reviewed. Ten patients have been excluded. Overall, 265 patients who
      underwent surgery under deep hypothermia and circulatory arrest in the "open
      technique" were divided retrospectively into two groups: those who underwent
      surgery with crossclamping of the ascending aorta during the cooling phase at the
      begin of the procedure (group 1, n = 191; 72.1 %) and those in whom the aorta was
      not clamped (group 2, n = 74; 27.9 %). RESULTS: Preoperative characteristics were
      similar in both groups. In group 1, femoral artery cannulation, composite graft
      repair, and aortic arch replacement were significantly more frequent. In-hospital
      mortality was 15.2 % in group 1 and 17.6 % in group 2 (P = not significant).
      Neurologic deficits were observed in 9.4% in group 1 and in 10.8% in group 2 (=
      not significant). There were no significant differences in clinical outcome
      between the two groups of patients. CONCLUSIONS: This study demonstrates that
      both options, aortic crossclamping or noclamping, may be used during the
      induction of deep hypothermia to repair acute type A aortic dissections with
      similar early clinical outcome. For the selection of the most appropriate
      technique, we recommend case by case evaluation, weighing the potential risks and
      benefits of aortic crossclamping.

PMID- 19114204
TI  - Effect of rosuvastatin pretreatment on myocardial damage after coronary surgery:
      a randomized trial.
AB  - OBJECTIVE: Myocardial disease without evidence of myocardial infarction is a
      frequent complication after cardiac surgery during cardiopulmonary bypass.
      Statins might be protective, but their efficacy has not been established in
      randomized trials. METHODS: Two hundred patients undergoing coronary surgery were
      enrolled. They were randomized to rosuvastatin (20 mg/d, n = 100) or placebo (n =
      100) starting 1 week before the operation. Troponin I, myoglobin, creatine kinase
      MB mass, and high-sensitivity C-reactive protein were used as markers of
      myocardial injury, and their values were determined at baseline and at regular
      intervals after the operation. Electrocardiography and echocardiography were
      performed before and after the operation. RESULTS: Myocardial disease was
      diagnosed when troponin I, myoglobin, and creatine kinase-MB mass values were
      above the upper normal limit without evidence of electrocardiographic changes,
      echocardiographic changes, or both. The percentages of marker level increase
      indicative of myocardial disease were determined in the placebo versus statin
      groups and were as follows: troponin I, 35% versus 65% (P < .0001); myoglobin,
      39% versus 72% (P < .0001); creatine kinase-MB mass, 22% versus 40% (P = .0002).
      Peak postoperative values of troponin I (0.16 +/- 0.15 vs 0.32 +/- 0.26 ng/mL, P
      = .0008), myoglobin (72.25 +/- 25 vs 98.31 +/- 31 ng/mL, P < .0001), and creatine
      kinase-MB mass (3.9 +/- 3.3 vs 9.3 +/- 8.1 ng/mL, P < .0001) were significantly
      higher in the placebo group. High-sensitivity C-reactive protein values were
      increased in 58% of pretreated versus 88% of the control patients (15.4 +/- 2.5
      vs 17.2 +/- 3.4 mg/L, P < .0001). In high-risk patients myocardial disease was
      observed more frequently but significantly less in statin-pretreated patients.
      CONCLUSIONS: Statin pretreatment reduces myocardial damage after coronary surgery
      and could improve both short- and long-term results.

PMID- 19114205
TI  - Congestive heart failure complicating aortic regurgitation with medical and
      surgical management: a prospective study of traditional and quantitative
      echocardiographic markers.
AB  - OBJECTIVE: Congestive heart failure complicating aortic regurgitation is poorly
      described, and predictive roles of quantitative versus traditional (symptoms or
      low ejection fraction) surgical markers are unclear. METHODS: We prospectively
      enrolled 287 patients with aortic regurgitation (age, 61 +/- 17 years; 68% male)
      in whom we performed quantitative Doppler echocardiographic analysis and personal
      physicians conducted management. RESULTS: After diagnosis, 40 congestive heart
      failure episodes occurred under medical management (10-year, 23% +/- 4%) causing
      high subsequent mortality (hazard ratio [HR], 2.8; 95% confidence interval [CI],
      1.2-6.8; P = .02). Patients with traditional surgical markers (symptoms or
      ejection fraction <50%) were surprisingly followed 1.4 +/- 3.3 years under
      medical management with frequent congestive heart failure (adjusted risk, 4.9;
      95% CI, 2.1-11.0; P < .001) and excess postoperative mortality (HR, 3.0; 95% CI,
      1.3-7.1; P = .01). Quantitative American Society of Echocardiography aortic
      regurgitation grading and left ventricular end-systolic volume index
      independently predicted congestive heart failure (quantitative American Society
      of Echocardiography severe aortic regurgitation: HR, 3.6; 95% CI, 1.3-13.0; P =
      .015; end-systolic volume index >or=45 mL/m(2): HR, 2.1; 95% CI, 1.03-4.4; P =
      .04) or death-congestive heart failure with incremental predictive value (P <
      .001). Higher congestive heart failure rates occurred with quantitative American
      Society of Echocardiography severe aortic regurgitation (regurgitant volume of
      >or=60 mL/beat or orifice of >or=30 mm(2)) versus quantitative American Society
      of Echocardiography mild aortic regurgitation (10-year: 44% +/- 10% vs 15% +/-
      7%, P < .001) and end-systolic volume index of 45 mL/m(2) or greater versus less
      than 45 mL/m(2) (33% +/- 7% vs 9% +/- 2%, P < .001). Traditional markers
      (symptoms and ejection fraction <50%) had lower sensitivity for congestive heart
      failure than quantitative echocardiography (all P < .001). Cardiac surgery for
      aortic regurgitation markedly reduced congestive heart failure in quantitative
      American Society of Echocardiography severe aortic regurgitation (HR, 0.23; 95%
      CI, 0.08-0.68; P = .008) without excess mortality (P = .10). CONCLUSION: This
      prospective study of aortic regurgitation shows frequent congestive heart failure
      under conservative management. Traditional surgical markers (symptoms and
      ejection fraction <50%) predict subsequent congestive heart failure but are
      insensitive, and rescue operations are often delayed and associated with excess
      mortality. Quantitative echocardiography provides congestive heart failure
      predictors that are independent, incremental, and more sensitive than traditional
      markers. Cardiac surgery for aortic regurgitation markedly reduces congestive
      heart failure rates in high-risk patients with aortic regurgitation.

PMID- 19114206
TI  - Endovascular treatment for acute traumatic transection of the descending aorta:
      focus on operative timing and left subclavian artery management.
AB  - OBJECTIVE: The operative timing and management of acute traumatic aortic rupture
      are matters of debate. We reviewed our experience with endovascular repair of
      acute traumatic aortic rupture, focusing on these topics. METHODS: From 1998 to
      2007, 31 patients were referred to our institute for acute traumatic rupture of
      the descending aorta. In 11 patients (group I) an early stent graft procedure was
      performed, whereas in 16 patients (group II) endovascular repair was delayed. The
      median time from trauma was 24 hours in group I and 1.5 months in group II. Eight
      (25.8%) patients had a short proximal neck (<5 mm from the left subclavian
      artery). Of these, 2 had the left subclavian artery totally covered by the
      endoprosthesis, and 2 had the left subclavian artery partially covered. Four
      patients with a posttraumatic pseudoaneurysm involving the left subclavian artery
      (3 patients) or the left common carotid artery (1 patient) underwent conventional
      open surgical intervention. RESULTS: Technical success was obtained in all
      patients. There were neither intraoperative nor perioperative deaths. Cerebellar
      stroke was detected in 1 patient after the intentional closure of the left
      subclavian artery. Follow-up (32.7 +/- 27.5 months) was 100% complete. No late
      deaths, endoleaks, or complications occurred. CONCLUSION: The endovascular
      approach was a safe and flexible procedure in traumatic aortic rupture and
      allowed us to fit the operative timing to every patient's clinical and imaging
      findings. In the presence of an inadequate proximal landing zone, conventional
      open surgical intervention still remains a favorable option as an alternative to
      endovascular procedures if a surgical revascularization of the left subclavian
      artery, carotid artery, or both is necessary.

PMID- 19114207
TI  - Reoperative minimal access aortic valve surgery: minimal mediastinal dissection
      and minimal injury risk.
AB  - OBJECTIVE: Minimizing surgical access in reoperative cardiac surgery allows
      limitation of dissection, trauma, and manipulation of patent bypass grafts. We
      report an 11-year experience with reoperative minimal access aortic valve surgery
      through an upper hemisternotomy. METHODS: From July 1996 to June 2007 at our
      institution, 146 patients underwent reoperative minimal access aortic valve
      surgery, 109 of whom had undergone previous coronary artery bypass grafting and
      93 of whom had a patent left internal thoracic artery graft. In patients with a
      patent left internal thoracic artery graft, the graft remained undissected.
      Myocardial protection was achieved with hypothermia, cold cardioplegia, and
      systemic hyperkalemia. Early and late outcomes were analyzed. RESULTS: Median age
      was 76 years, and 43 patients (29%) were 80 years or older. Nineteen
      patients(13%) underwent concomitant procedures, such as coronary artery bypass
      grafting, mitral valve repair, and ascending aortic replacement. Median
      cardiopulmonary bypass and aortic crossclamp times were 150 and 80 minutes,
      respectively. Four patients (2.8%) had conversion to full sternotomy. Operative
      mortality was 4.1% (6/146). The incidences of reoperation for bleeding and blood
      transfusion were 0.7% (1/146) and 83.6% (122/146), respectively. No patient had
      left internal thoracic artery or aortocoronary graft injury. Median stay was 8
      days, and 56% (79/140) were discharged home. Five-year actuarial survival was
      85%. CONCLUSION: An upper hemisternotomy approach for reoperative aortic valve
      surgery is safe and feasible. This approach minimizes tissue dissection and
      trauma, thereby reducing the risk of injury to patent grafts and mediastinal
      organs.

PMID- 19114208
TI  - Airway stenoses after lung transplantation: incidence, management, and outcome.
AB  - OBJECTIVE: Airway stenoses have been a significant cause of morbidity and
      mortality after lung transplantation. We reviewed our 11-year experience with
      dilatation and silicone stent treatment of airway strictures after lung
      transplantation. We adopted this approach after managing the complications of
      nitinol/wire mesh stents, including stent fracture, granulation tissue
      overgrowth, and difficulty with removal. METHODS: Between January of 1996 and
      December of 2007, 240 patients underwent lung transplantation (132 single lung,
      108 double lung; 121 male, 119 female; mean age 49.4 +/- 12.9 years). Twenty
      patients (8.3%) developed >50% stenosis in 22 airways over 35 to 135 days
      following surgery. Short and long-segment strictures were managed with rigid
      bronchoscopy, mechanical/laser debridement, balloon dilatation, and silicone
      stent placement. Mean follow-up was 4.9 +/- 3.5 years after stent removal.
      RESULTS: The mean time to diagnosis of airway stenosis was 81.5 +/- 26.9 days.
      Pulmonary aspergillosis and pseudomonal infection, age less than 45 years, and
      early rejection correlated with airway stenosis; however, ischemic time, side of
      transplant, and preoperative disease did not. Airway patency and symptom
      improvement were achieved in 18 of 20 patients. Sixteen patients were able to
      have their stents removed at a mean of 362.3 +/- 126.4 days with permanent
      resolution of airway stenosis. Overall survival was similar for patients with and
      without airway stenosis. CONCLUSION: Airway stenosis after lung transplantation
      can be successfully managed with bronchoscopic dilatation and temporary silicone
      stent placement. With time, most short and long airway stenoses resolve with
      atraumatic stenting of the affected areas. Removal of stents with permanent
      airway patency is achievable in most lung transplant recipients with airway
      stenosis.

PMID- 19114209
TI  - Blockade of receptor for advanced glycation end product attenuates pulmonary
      reperfusion injury in mice.
AB  - OBJECTIVE: The receptor for advanced glycation end products (RAGE) is expressed
      at high levels in the lung, particularly in type 1 alveolar cells, and has been
      shown to amplify injury triggered by acute stress. Previous studies suggest serum
      concentrations of soluble RAGE increase during pulmonary reperfusion injury after
      transplantation. RAGE blockade has been shown to suppress hepatic and cardiac
      ischemia and reperfusion injury in mice. Thus we tested the hypothesis that RAGE
      mediates tissue-injury mechanisms in ischemia and reperfusion injury in the lung.
      METHODS: C57BL/6 mice were subjected to 30 minutes of pulmonary ischemia by
      clamping the left hilum, followed by 60 minutes of reperfusion. Lung function was
      assessed by means of blood gas analysis, and capillary leak was assessed by
      injecting fluorescein isothiocyanate-labeled albumin and comparing fluorescence
      in bronchial lavage fluid with that in serum. Histologic analysis of the lung was
      performed by a pathologist naive to the experimental conditions. RESULTS: In
      animals subjected to RAGE blockade, significant increases in Po(2) (108 vs 73 mm
      Hg, P = .0094) and more than 3-fold decrease in capillary leak Relative
      Fluorescent Units (RFU, 6.12 vs 1.75; P = .001) were observed. Histologic
      examination revealed significant injury reduction in soluble RAGE-treated animals
      versus control animals. RAGE knockout mice exhibited a protected phenotype when
      exposed to pulmonary ischemia and reperfusion. Additionally, interleukin 8
      production and nuclear factor kappaB activation were increased in control mice.
      CONCLUSION: Abrogation of RAGE signaling attenuates pulmonary ischemia and
      reperfusion injury. This study suggests that RAGE might play a central role in
      pulmonary reperfusion injury and in transplantation and that blockade of RAGE
      might offer a potential target to abrogate pulmonary reperfusion injury in
      clinical transplantation.

PMID- 19114210
TI  - A Rho-kinase inhibitor improves cardiac function after 24-hour heart
      preservation.
AB  - OBJECTIVE: The Rho-kinase signaling pathway is associated with coronary
      vasculopathy and myocardial dysfunction after cardiac transplantation. This study
      evaluated whether using a Rho-kinase inhibitor during allograft storage could
      limit early endothelial dysfunction and improve myocardial performance after
      reperfusion. METHODS: This experiment was performed with an isolated working
      rabbit heart model and a support rabbit. Donor hearts (control group, n = 8) were
      arrested with an extracellular type of cardioplegia, preserved with University of
      Wisconsin solution, and then immersed in University of Wisconsin solution for 24
      hours (1 degrees C). The Rho-kinase inhibitor (Rho-kinase inhibitor group, n = 8)
      was administrated in the cardioplegic solution, the preservation University of
      Wisconsin solution, and the storage University of Wisconsin solution. Left
      ventricular performance was evaluated from the modified Frank-Starling curve in
      the working mode. Coronary blood flow and donor heart rate were measured in
      Langendorff mode. Effective evaluation of the Rho-kinase inhibitor was inferred
      from phosphorylated myosin light chain. The expression of endothelial nitric
      oxide synthase mRNA was analyzed to assess endothelial function. RESULTS: The
      Frank-Starling curve showed a significant left and upward shift in the Rho-kinase
      inhibitor group compared with the control group (P < .05). The coronary blood
      flow and heart rate in the Rho-kinase inhibitor group at 120 minutes was
      significantly higher than in the control group (P < .05). Phosphorylated myosin
      light chain was significantly suppressed in the Rho-kinase inhibitor group (P <
      .05). Endothelial nitric oxide synthase mRNA levels in the Rho-kinase inhibitor
      group increased 4-fold relative to those seen in the control group. CONCLUSIONS:
      Treatment with Rho-kinase inhibitor during allograft harvest and storage enhanced
      coronary blood flow and ventricular recovery through nitric oxide-dependent
      endothelial protection after reperfusion. Rho-kinase inhibitor could help prevent
      early myocardial dysfunction after transplantation.

PMID- 19114211
TI  - The unmasking of a Brugada phenotype after pulmonary resection: a case report and
      implications for postoperative management.

PMID- 19114212
TI  - A word of caution regarding patients with hypoplastic left heart syndrome and a
      diminutive aorta.

PMID- 19114213
TI  - Artificial chordae: a simple clip and tie technique.

PMID- 19114214
TI  - Reversed L-shaped deformity of the anterior mitral leaflet and its reparative
      technique.

PMID- 19114215
TI  - Noninvasive assessment of cardiac function during ventricular assist system
      support using 64-row multidetector computed tomographic angiography.

PMID- 19114217
TI  - Bicuspid aortopathy or bicuspid aortopathies? The risk in generalizing.

PMID- 19114218
TI  - Computed tomography and endoscopic ultrasound in detection and characterization
      of mediastinal masses.

PMID- 19114219
TI  - Surgeons' informed consent.

PMID- 19114222
TI  - Anxiolytic effects of a yoga program in early breast cancer patients undergoing
      conventional treatment: a randomized controlled trial.
AB  - OBJECTIVES: This study compares the anxiolytic effects of a yoga program and
      supportive therapy in breast cancer outpatients undergoing conventional treatment
      at a cancer centre. METHODS: Ninety-eight stage II and III breast cancer
      outpatients were randomly assigned to receive yoga (n=45) or brief supportive
      therapy (n=53) prior to their primary treatment i.e., surgery. Only those
      subjects who received surgery followed by adjuvant radiotherapy and six cycles of
      chemotherapy were chosen for analysis following intervention (yoga, n=18,
      control, n=20). Intervention consisted of yoga sessions lasting 60min daily while
      the control group was imparted supportive therapy during their hospital visits as
      a part of routine care. Assessments included Speilberger's State Trait Anxiety
      Inventory and symptom checklist. Assessments were done at baseline, after
      surgery, before, during, and after radiotherapy and chemotherapy. RESULTS: A GLM
      repeated measures ANOVA showed overall decrease in both self-reported state
      anxiety (p<0.001) and trait anxiety (p=0.005) in yoga group as compared to
      controls. There was a positive correlation between anxiety states and traits with
      symptom severity and distress during conventional treatment intervals.
      CONCLUSION: The results suggest that yoga can be used for managing treatment
      related symptoms and anxiety in breast cancer outpatients.

PMID- 19114223
TI  - The effectiveness of wet-cupping for nonspecific low back pain in Iran: a
      randomized controlled trial.
AB  - OBJECTIVES: To determine the efficacy of wet-cupping for treating persistent
      nonspecific low back pain. BACKGROUND: Wet-cupping therapy is one of the oldest
      known medical techniques. It is still used in several contemporary societies.
      Very minimal empirical study has been conducted on its efficacy. DESIGN:
      Randomized controlled trial with two parallel groups. Patients in the
      experimental group were offered the option of referral to the wet-cupping
      service; all accepted that option. The control group received usual care.
      SETTING: Medical clinic in Kermanshah, Iran. PARTICIPANTS: In total, 98 patients
      aged 17-68 years with nonspecific low back pain; 48 were randomly assigned to
      experimental group and 50 to the control group. INTERVENTION: Patients in the
      experimental group were prescribed a series of three staged wet-cupping
      treatments, placed at 3 days intervals (i.e., 0, 3, and 6 days). Patients in the
      control group received usual care from their general practitioner. MAIN OUTCOME
      MEASURES: Three outcomes assessed at baseline and again 3 months following
      intervention: the McGill Present Pain Index, Oswestry Pain Disability Index, and
      the Medication Quantification Scale. RESULTS: Wet-cupping care was associated
      with clinically significant improvement at 3-month follow-up. The experimental
      group who received wet-cupping care had significantly lower levels of pain
      intensity ([95% confidence interval (CI) 1.72-2.60] mean difference=2.17,
      p<0.01), pain-related disability (95% CI=11.18-18.82, means difference=14.99,
      p<0.01), and medication use (95% CI=3.60-9.50, mean difference=6.55, p<0.01) than
      the control group. The differences in all three measures were maintained after
      controlling for age, gender, and duration of lower back pain in regression models
      (p<0.01). CONCLUSIONS: Traditional wet-cupping care delivered in a primary care
      setting was safe and acceptable to patients with nonspecific low back pain. Wet
      cupping care was significantly more effective in reducing bodily pain than usual
      care at 3-month follow-up.

PMID- 19114224
TI  - Resin from the mukul myrrh tree, guggul, can it be used for treating
      hypercholesterolemia? A randomized, controlled study.
AB  - BACKGROUND: Guggul, herbal extract from resin of the Commiphora mukul tree, is
      widely used in Asia as a cholesterol-lowering agent based on Indian Ayurvedic
      medicine. Its popularity for this use is increasing in the US and Western Europe.
      Guggulsterones, the presumed bioactive compounds of guggul, may antagonise two
      nuclear hormone receptors involved in cholesterol metabolism, which is a possible
      explanation for hypolipidemic effects of these extracts. However, publications of
      efficacy data on the use of guggul extracts in Western populations are scarce.
      OBJECTIVE: To study the efficacy of a guggul-based formulation (short: guggul) on
      blood lipids in healthy adults with moderately increased cholesterol. METHODS:
      Double-blind, randomised, placebo controlled trial in Norwegian general practice.
      43 women and men, age 27-70, with moderately increased cholesterol, randomised to
      use 2160mg guggul (4 capsules) daily, or placebo for 12 weeks. OUTCOME MEASURES:
      Mean change in total cholesterol, low-density lipoprotein cholesterol (LDL-C),
      triglycerides, high-density lipoprotein cholesterol (HDL-C) and total
      cholesterol/HDL-C ratio compared with baseline. Lipids were analysed at baseline,
      and at 6 and 12 weeks. In addition, unexpected events and adverse effects were
      recorded. RESULTS: Two dropouts, one withdrawal, and incomplete lab results for
      six persons left 34 participants to accomplish the trial (18-guggul, 16-placebo)
      with complete lab test data. After 12 weeks, mean levels of total cholesterol and
      HDL-C in the active group were significantly reduced compared with the placebo
      group. However, the mean levels of LDL-C, triglycerides, and total
      cholesterol/HDL-C ratio between the two groups did not change significantly. Ten
      guggul users (vs. four in the placebo group) reported side effects: mild
      gastrointestinal discomfort (n=7), possible thyroid problems (n=2), and
      generalized skin rash (n=1). The latter resulted in withdrawal from trial.
      CONCLUSIONS: Even if total cholesterol and HDL-C were significantly reduced, the
      clinical magnitude of this remains obscure. More and larger studies are needed to
      establish effects and safety of guggul-based formulations in the treatment for
      hypercholesterolemia.

PMID- 19114225
TI  - Effectiveness of traditional bone setting in treating chronic low back pain: a
      randomised pilot trial.
AB  - OBJECTIVES: The aim of this trial was to establish the effectiveness of
      traditional bone setting (TBS) compared with conventional physical and exercise
      therapy (PhT) in treating chronic low back pain (cLBP). DESIGN: Randomised
      clinical trial. SETTING: Working-aged cLBP patients (n=131, age range 29-51
      years) were randomised into two treatment groups: TBS and PhT. Follow-up
      assessments took place 1, 6 and 12 months after treatment. INTERVENTIONS: TBS is
      a popular traditional manual mobilisation therapy for musculoskeletal disorders
      in Finland. Conventional PhT was used as the reference treatment. MAIN OUTCOME
      MEASURES: LBP intensity (Visual Analog Scale 0-100, VAS), the Oswestry Disability
      Index (ODI), the global assessment score (scale -1 to +10), a health-related
      quality of life (HRQoL) assessment and spine mobility measurements were used as
      measures. RESULTS: 118 patients (95.9%, 59 men and 59 women) completed the
      treatment program. Both treatments reduced the VAS and ODI levels after 1 month.
      Changes in VAS did not differ between the two treatment groups (mean -0.2, CI 
      11.3 to 10.9). The improvement in ODI (mean 2.4, CI -1.2 to 6.0, p=0.069,
      repeated measurements ANOVA) and quality of life scores (mean -0.03, CI -0.06 to
      0, p=0.056) tended to be greater after TBS. Additionally, global assessment
      scores were better for TBS-treated patients (Mann-Whitney test, p=0.001). There
      were no differences between the spine mobility test results of the two groups.
      Changes in both VAS (mean -2.4, CI -15.5 to 10.6) and ODI (mean 1.0, CI -3.0 to
      5.1) measures did not, however, differ between the groups at the 1-year follow-up
      stage. CONCLUSIONS: Most cLBP patients found the treatments to be beneficial.
      Although the long-term dynamics of pain and disability did not differ between the
      groups, the subjective benefits appeared to be more significant after TBS.

PMID- 19114226
TI  - Is the content of the Chinese Quality of Life Instrument (ChQOL) really valid in
      the context of traditional Chinese medicine in Hong Kong?
AB  - BACKGROUND: Content validity is crucial in quality of life instrument development
      but there is very little literature on this in Chinese culture. The Chinese
      Quality of Life Instrument (ChQOL) was developed in Mainland China to capture the
      health-related quality of life (HRQOL) concepts specific to traditional Chinese
      medicine (TCM). The aim of this study was to evaluate the content validity of
      ChQOL in a Chinese population whose spoken dialect and health-care system are
      different from those of Mainland China to find out whether the instrument is
      generalizable. METHODS: 8 TCM practitioners and 10 patients rated the clarity,
      relevance and appropriateness of each of the 50 items of the ChQOL (HK version),
      and completed qualitative cognitive debriefing interviews. RESULTS: The content
      of ChQOL was rated valid by TCM practitioners with CVIs on clarity, relevance and
      appropriateness ranging from 80 to 100%. 49 out of 50 items were well understood
      by patients, but 12 items had CVI on relevance and 5 items had CVI on
      appropriateness lower than 70% among patients. After reviewing the patients and
      TCM practitioners' opinions, revisions were made for three items (2, 8 and 29) to
      form the ChQOL (HK version)-2008. In general, the ChQOL was found to be too long
      which called for shorter version. CONCLUSIONS: The content of ChQOL was shown to
      be really valid in the context of Chinese Medicine for Cantonese speaking
      Chinese. There was some discrepancy between the judgments of TCM practitioners
      and patients indicating the importance of evaluation by both experts and lay
      persons.

PMID- 19114228
TI  - Herbal medicines: prevalence and predictors of use among Malaysian adults.
AB  - OBJECTIVE: The aim of this study was to examine the prevalence and identify
      factors, which predict the use of herbal medicines among Malaysian adults.
      METHODS: Using a cross-sectional design, data were collected via face-to-face
      interview using structured questionnaire from convenience sample of adults from
      four towns in Malaysia. Multivariate logistic regression analysis was used to
      identify the significant predictors of herbal medicines use. RESULTS: From a
      total of 1601 respondents, 542 (33.9%) reported use of herbal medicines in the
      previous 12 months. Multivariate logistic regression analysis revealed the
      following variables to be predictive of herbal medicines use: female gender [odds
      ratio (OR) 1.80, confidence interval (CI) 1.40-2.31], being married [OR 1.97, CI
      1.44-2.71], having health problems [OR 2.31, CI 1.74-3.07] and having high-income
      levels [OR 4.21, CI 1.72-10.30]. The odds of someone using herbal medicines also
      increases though slightly if someone has favorable opinions about herbal
      medicines on the aspects examined. On the other hand, being Chinese [OR 0.74, CI
      0.57-0.96] and Indians [OR 0.17, CI 0.11-0.27] were associated with decreased
      odds of using herbal medicines compared to Malays. CONCLUSION: The prevalence of
      herbal medicines use is high. Respondents' personal attributes and opinions
      influence their likelihood of using herbal medicines. These findings are
      important because knowledge of the predictors of herbal medicines use may help
      health care providers to identify patients at increased risk who would be
      candidates for receiving guidance on safe use of herbal medicines.

PMID- 19114227
TI  - Dietary supplementation by Japanese patients with chronic obstructive pulmonary
      disease.
AB  - OBJECTIVES: To investigate the prevalence and type of dietary supplements taken
      by Japanese patients with chronic obstructive pulmonary disease (COPD) and
      factors affecting their use. DESIGN: Cross-sectional study by face-to-face
      interviews. SETTING: Six hospitals in central Japan. PARTICIPANTS: Of the 300
      referred COPD patients aged between 50 and 75 years, 278 eligible participants
      (244 men and 34 women) with complete data were available for analysis. MAIN
      OUTCOME MEASURES: Prevalence of supplement use, dietary supplement categories
      (multivitamin, beta-carotene, vitamin C, vitamin E, and miscellaneous). RESULTS:
      Overall, 42% of participants were dietary supplement users taking at least one
      category of supplements weekly; the prevalence being higher for female (47%) than
      male patients (41%). The most common supplements consumed were energy drink for
      men (11.1%), and multivitamin (11.8%) and vinegar (11.8%) for women. Dietary
      supplementation was found to be affected by age (p=0.04), COPD severity (p=0.03)
      and presence of co-morbidity (p=0.03). Older patients over 60 years were more
      likely to take dietary supplements (odds ratio (OR) 2.44, 95% CI 1.03-5.80),
      whereas severe COPD patients (OR 0.41, 95% CI 0.18-0.95) and those with a co
      morbidity (OR 0.54, 95% CI 0.32-0.94) tended not to use. CONCLUSIONS: Dietary
      supplements are popular for patients with COPD especially among older patients.
      The findings are important to clinical trials and experimental interventions
      advocating nutritional supplementation therapy for pulmonary rehabilitation.

PMID- 19114229
TI  - Haishengsu as an adjunct therapy to conventional chemotherapy in patients with
      non-small cell lung cancer: a pilot randomized and placebo-controlled clinical
      trial.
AB  - OBJECTIVE: To investigate the effect of Haishengsu, an extract from Tegillarca
      granosa, on non-small cell lung cancer as an adjunct to conventional
      chemotherapy. DESIGNS/SETTINGS: Randomized, double-blind, placebo-controlled
      trial was conducted in 83 patients. The Haishengsu (n=42, 2.4mg Haishengsu in
      250ml normal saline, iv, for 15 days) and the placebo group (n=41, 250ml normal
      saline, iv) were also treated with two cycles (28 days for each cycle) of
      conventional chemotherapy consisting mitomycin, vindesine and cisplatin. RESULTS:
      The curative effect of conventional chemotherapy was observed in 62% of
      Haishengsu group patients and in 39% in of the placebo group patients (P=0.04, RR
      1.59, 95% CI: 1.01-2.49). Improvement in Karnofsky performance status scores was
      seen in 66.7% of Haishengsu group patients and in 17.1% of the placebo group
      patients (P<0.01, RR 3.63, 95%CI: 1.77-7.41). The ratio of patients with no or
      only mild gastrointestinal reaction in the Haishengsu and the placebo group was
      83.3% and 39.0%, respectively (P<0.01, RR 2.13, 95% CI: 1.42-3.20). CONCLUSIONS:
      This study suggests that Haishengsu may be an effective adjunct therapy to the
      conventional chemotherapy for non-small cell lung cancer. The short-term
      therapeutic effect of chemotherapy may be improved and the chemotherapy-induced
      nausea or vomiting may be reduced by concurrent Haishengsu administration.

PMID- 19114230
TI  - Chondroitin sulphate: a complex molecule with potential impacts on a wide range
      of biological systems.
AB  - Chondroitin sulphate (CS) is widely consumed orally by humans, and non-humans as
      it is believed to be beneficial for those with joint-related pathologies. Data
      concerning the functions of chondroitin sulphate in this, and other, biological
      systems are being actively extended. However, it is important to appreciate that
      chondroitin sulphate molecules represent a heterogeneous population the structure
      of which varies with source. As commercially available chondroitin sulphate is
      derived from a range of sources, and the molecular functions of chondroitin
      sulphate depend upon the structure, there are a range of structures available
      with differing potential for therapeutic impacts on a range of pathologies. While
      the safety of CS is not presently in doubt, poor quality finished products have
      the potential to compromise clinical and lab-based studies and will fail to give
      consumers all of the benefits available. Major parameters including
      bioavailability and uptake have been studied but it is clear that significant
      challenges remain in the identification of composition, sequence and size impacts
      on function, understanding how the consumed material is altered during uptake and
      travels to a site of action and how it exerts an influence on biological
      processes. If we understand these factors it may be possible to predict impacts
      upon biological processes and identify specific chondroitin sulphate structures
      which may target specific pathologies.

PMID- 19114231
TI  - Delivering diversity: newly regulated midwifery returns to Manitoba, Canada, one
      community at a time.
AB  - Through its publicly funded health care system, Canada is committed to offering
      accessible, quality maternity health services to all its citizens, yet this
      remains a challenge in its First Nations, rural and immigrant communities. With
      the implementation of midwifery as a self-regulating health profession in
      Manitoba, Canada, in 2000, initiatives were incorporated into the structure of
      the profession to try to address this issue. This qualitative investigation
      documents and explores these initiatives through a case study combining
      semistructured interviews and documentary sources. The innovations discussed
      include the development of an Aboriginal midwifery degree program, the supports
      put in place to assist rural midwifery practices, and the efforts to increase
      ethnic diversity and cultural competence within the midwifery profession. What
      unites these efforts is a community building approach which attempts to
      strengthen communities through local midwifery services and midwives drawn from
      community members.

PMID- 19114232
TI  - With woman: midwifery care of women with unintended pregnancies.

PMID- 19114233
TI  - When politics trumps evidence: legislative or regulatory exclusion of abortion
      from advanced practice clinician scope of practice.

PMID- 19114235
TI  - Hearing screening for newborns: the midwife's role in Early Hearing Detection and
      Intervention.
AB  - Universal newborn hearing screening is becoming the standard of care in the
      United States. However, there has been some controversy around this pediatric
      preventive health care practice. In 2001, the US Preventative Services Task Force
      (USPSTF), the leading independent panel of experts on prevention and primary care
      in the United States, reviewed the scientific literature and found inconclusive
      evidence to recommend for or against universal newborn hearing screening. As a
      result of this lack of recommendation, some pediatric providers were not
      screening the hearing of all newborn infants. The USPSTF released an update in
      July 2008 concluding there is scientific evidence to recommend newborn hearing
      screening for all infants. Universal newborn hearing screening is the first step
      in the national Early Hearing Detection and Intervention (EHDI) program. EHDI
      includes not only universal newborn hearing screening but also diagnostic
      evaluation for any infant failing the initial hearing screen and intervention
      services for any infant diagnosed with hearing loss. During the prenatal and
      postnatal periods, obstetric care providers can play a vital role in the EHDI
      process through education, screening, referral, and assistance with follow-up.
      Through these services, clinicians can work with parents and pediatric care
      providers to help newborns and infants develop communication and language skills
      that will last a lifetime.

PMID- 19114236
TI  - Introduction of CenteringPregnancy in a public health clinic.
AB  - CenteringPregnancy is a promising group visit prenatal care innovation that
      provides substantial health promotion content. Elements unique to group care
      include peer support and self-management training and activities.
      CenteringPregnancy was introduced at a large public health clinic serving
      predominantly low-income African American pregnant women. All prenatal care at
      this clinic was provided by certified nurse-midwives, and all providers were
      trained in the CenteringPregnancy model. One hundred and ten women received
      prenatal care in CenteringPregnancy groups. Focus groups of pregnant women,
      providers, and health center staff reported that the program benefited women
      despite implementation challenges such as scheduling changes. Compared to women
      in individual care, women in CenteringPregnancy had significantly more prenatal
      visits, increased weight gain, increased breast feeding rates, and higher overall
      satisfaction. This pilot project demonstrated that CenteringPregnancy can be
      implemented in a busy public health clinic serving predominantly low-income
      pregnant women and is associated with positive health outcomes.

PMID- 19114234
TI  - The interaction between chronic stress and pregnancy: preterm birth from a
      biobehavioral perspective.
AB  - Women's health care providers are increasingly aware that chronic stressors--such
      as poverty, ongoing perceived stress and anxiety, intimate partner violence, and
      experiences of racism--are associated with an increased incidence of preterm
      birth in the United States. It is important to increase our understanding of the
      explanatory pathways involved in these associations. This article discusses the
      concepts of stress, chronic stress response, allostatic load, the physiology of
      labor initiation, and the pathophysiologic interactions that may contribute to
      the occurrence of chronic stress-related preterm birth. Implications for future
      research and interventions are explored.

PMID- 19114237
TI  - Racial disparities in biopsychosocial factors and spontaneous preterm birth among
      rural low-income women.
AB  - In this descriptive prospective study, 269 African American, Hispanic, and
      Caucasian women from rural prenatal clinics were interviewed once between 16 and
      28 weeks' gestation. Associations between biopsychosocial risk factors and
      preterm birth (PTB) were examined. African American women with spontaneous PTB
      were more likely to be older, and to have higher Bowman Gray Risk Index scores
      and hypertensive diseases of pregnancy than African American women who did not
      have a spontaneous PTB. There were significant differences in bacterial
      vaginosis, hypertensive diseases of pregnancy, smoking, social support from
      others, and self-esteem among the three racial groups. In the total sample after
      adjustment for sociodemographic and biopsychosocial factors, women with
      spontaneous PTB were three times more likely to be African American, to have
      oligohydramnios, hypertensive diseases of pregnancy, and had higher Bowman Gray
      Risk Index scores than the total sample of women without spontaneous PTB.
      Understanding the risks associated with spontaneous PTBs that are unique to
      African American women and why biopsychosocial risk factors vary by racial/ethnic
      group may lead to tailored interventions.

PMID- 19114238
TI  - Frequency, severity, and effect on life of physical symptoms experienced during
      pregnancy.
AB  - This study aimed to: 1) describe the number, frequency, severity of discomfort
      and effect of symptoms on life of 29 physical symptoms women experienced at 15 to
      25 weeks of gestation; 2) explore whether experiencing this group of physical
      symptoms more frequently and intensely was associated with a higher score of
      depressive symptoms and lower self-esteem; (3) examine whether discomfort and
      effect ratings aided prediction of well being over and above symptom frequency;
      and (4) investigate which individual physical symptoms contributed most to
      predicting depressive symptoms and self-esteem. Pregnant women (n = 215)
      completed the Beck Depression Inventory, Rosenberg Self-Esteem Scale, and a
      physical symptoms questionnaire. Frequency, discomfort, and the effect of
      physical symptoms all consistently correlated with higher scores for depressive
      symptoms, but less consistently with lower self-esteem. Discomfort and the effect
      of symptoms predicted variance in depressive symptoms after accounting for
      symptom frequency. Higher frequency, more discomfort, and the effect of fatigue
      and effect of flatulence were related to depressive symptoms. Relationships
      between pregnancy-related physical symptoms, depressive symptoms, and low self
      esteem suggest that when women report any of these constellation of factors,
      further screening is indicated. A comprehensive assessment of physical symptoms
      includes frequency, discomfort, and effect on life.

PMID- 19114239
TI  - Postpartum depression and help-seeking behavior.
AB  - The objective of this analysis was to investigate the demographic differences
      between women who report postpartum depression symptoms (PPDS) and seek help
      versus those who report symptoms but who do not seek help, using data from the
      Utah Pregnancy Risk Assessment Monitoring System (PRAMS) 2004 dataset. Overall,
      14.7% of Utah women reported experiencing PPDS in 2004. Sixty percent of the
      women who reported having PPDS did not seek help. Seeking help for depression
      during pregnancy was associated with help-seeking behavior postpartum (adjusted
      odds ratio [aOR] = 0.1; 95% confidence interval [CI], 0.04-0.2). Other factors
      associated with seeking help included having an infant admitted to the intensive
      care unit (aOR = 0.4; 95% CI, 0.2-0.9) and rural residency (aOR = 0.3; 95% CI,
      0.2-0.7). Nonwhite women were 12.1 times (95% CI, 3.0-48.5) more likely to not
      seek help for depression compared to white women. Further, Hispanic women (aOR =
      3.2; 95% CI, 1.3-8.1) and women who experienced emotional abuse had increased
      odds of not seeking help (aOR = 2.9; 95% CI, 1.3-6.2). Nearly 15% of Utah women
      in this study reported PPDS, yet fewer than half sought help. Target populations,
      such as nonwhite, Hispanic, emotionally abused, and urban women, have been
      identified for public health interventions.

PMID- 19114240
TI  - Midwifery and health disparities: theories and intersections.
AB  - In the past decade, the reduction of health disparities has become an important
      policy agenda in the United States. Clinicians in practice, however, may be
      unfamiliar with the prevailing causal theories and uncertain about what they can
      do to help to reduce inequalities in health. The purpose of this article is to
      provide women's health care clinicians with an overview of the definitions,
      measurement issues, and theories that fall under the rubric of health
      disparities. The intersecting roles of genetics, race/ethnicity, environment, and
      gender are discussed. The article also provides practical suggestions for
      interventions and health policy change that can be implemented by clinicians in
      practice.

PMID- 19114241
TI  - Clinical decision-making for repair of spontaneous childbirth trauma: validation
      of cues and related factors.
AB  - From recalled childbirth cases, a series of cues and related factors were
      previously identified that were used by midwives when making decisions to suture
      or not suture perineal and associated trauma incurred during spontaneous vaginal
      delivery. This study aimed to determine the validity of these cues and related
      factors. A panel of 18 experienced midwives evaluated their content validity
      using the criteria of "necessity" and "sufficiency." The two main cue categories
      "bleeding" and "birth trauma"-were considered by 18 (100%) of the panel members
      to be necessary to assess. At least 16 (89%) panel members considered the
      following specific cues necessary to assess: in the bleeding category-type, flow,
      amount, and effect of application of pressure or ice; in the birth trauma
      category-trauma sites, trauma types, dimensions of trauma, types of tissue,
      alignment of tissue, edema, and bruising. Seventeen (94%) panel members
      considered seven woman-centred related factors that were necessary to assess and
      14 (78%) considered the combination of all cues in bleeding, birth trauma, and
      related factors sufficient for making the decision to suture or not. The
      availability of these validated cues and related factors has the potential to
      guide a comprehensive assessment on which the decision to suture or not suture
      depends. This addition to the domain of midwifery knowledge enables educational
      preparation of midwives who will have the capacity to more adequately support
      women in childbirth.

PMID- 19114242
TI  - Nutrition and mental health in early pregnancy: a pilot study.
AB  - A pilot study was conducted to explore the dietary quality and maternal
      psychosocial status during the early weeks of pregnancy in a convenience sample
      of women (N = 13) recruited from two Planned Parenthood Clinics. Women were
      between 19 and 31 years of age, having their first pregnancy, and were on average
      7 weeks pregnant. Average caloric intake was 2653 kcal/day consisting of 34% fat.
      Six of the women had inadequate intake of calcium (x = 800 mg) and 11 had low
      iron intake (x = 20 mg). Dietary Quality Index-Pregnancy scores were below
      recommendations and six women had scores indicating a major depression. Dietary
      intakes of these low-income women early in pregnancy did not meet recommendations
      for pregnancy. Identifying factors that are related to poor dietary intake, such
      as low-income and the presence of depression, in early pregnancy may promote
      timely recognition of women in need of comprehensive monitoring throughout the
      pregnancy.

PMID- 19114243
TI  - The practice of prelacteal feeding to newborns among Hindu and Muslim families.

PMID- 19114244
TI  - Not my child: parental refusal of vaccinations for children.

PMID- 19114250
TI  - Use of hyaluronidase to prevent perineal trauma during spontaneous delivery: a
      pilot study.

PMID- 19114252
TI  - Births attended by certified nurse-midwives in the United States in 2005.

PMID- 19114253
TI  - A return to sanity.

PMID- 19114254
TI  - Yet another change is needed.

PMID- 19114255
TI  - Hurricanes, stress, and mindfulness.

PMID- 19114257
TI  - Benefiting from Explore.

PMID- 19114256
TI  - Pediatric obesity.

PMID- 19114258
TI  - Coalition forming to support IOM's Summit on Integrative Medicine.

PMID- 19114259
TI  - Trends that will affect your future... Genius.

PMID- 19114260
TI  - What traditional indigenous elders say about cross-cultural mental health
      training.
AB  - Although a number of authors have commented on what mental health practitioners
      should be taught to be effective and appropriate with indigenous people, rarely
      have traditional healers been asked for their views. This paper explores what a
      diverse group of traditional healing elders believe are the important attributes
      for mental health providers to embrace and what principles they should adopt to
      guide their training. How indigenous people understand the meaning of mental
      health is also examined. The research presented was conducted in preparation for
      developing a cross-cultural training program for human service providers that
      would include traditional elders as community mentors and adjunct faculty on
      equal status with academically trained faculty. The goal is to identify and
      summarize the core values and principles needed to train mental health providers
      to work in harmony with traditional healers. The term indigenous used in this
      paper refers to people who have lived in a place long enough to develop local
      knowledge and practices about that place, even though they might not have been
      the original inhabitants. For example, the Dene in Arizona are indigenous even
      though they have only occupied that area from about 1100 ad. Last, the paper is
      presented in an indigenous way, first by situating the author, telling a story,
      explaining the methodology, describing the elders and what they said, and ending
      with a story to dramatize the conclusions as indigenous elders would do.

PMID- 19114261
TI  - Mindfulness meditation and cognitive behavioral therapy for insomnia: a
      naturalistic 12-month follow-up.
AB  - A unique intervention combining mindfulness meditation with cognitive behavioral
      therapy for insomnia (CBT-I) has been shown to have acute benefits at
      posttreatment in an open label study. The aim of the present study was to examine
      the long-term effects of this integrated intervention on measures of sleep and
      sleep-related distress in an attempt to characterize the natural course of
      insomnia following this treatment and to identify predictors of poor long-term
      outcome. Analyses were conducted on 21 participants, who provided follow-up data
      at six and 12 months posttreatment. At each time point, participants completed
      one week of sleep and meditation diaries and questionnaires related to
      mindfulness, sleep, and sleep-related distress, including the Pre-Sleep Arousal
      Scale, the Glasgow Sleep Effort Scale, the Kentucky Inventory of Mindfulness
      Skills, and the Insomnia Episode Questionnaire. Analyses examining the pattern of
      change across time (baseline, end of treatment, six months, and 12 months)
      revealed that several sleep-related benefits were maintained during the 12-month
      follow-up period. Participants who reported at least one insomnia episode (>or=1
      month) during the follow-up period had higher scores on the Pre-Sleep Arousal
      Scale (P < .05) and the Glasgow Sleep Effort Scale (P < .05) at end of treatment
      compared with those with no insomnia episodes. Correlations between mindfulness
      skills and insomnia symptoms revealed significant negative correlations (P < .05)
      between mindfulness skills and daytime sleepiness at each of the three time
      points but not with nocturnal symptoms of insomnia. These results suggest that
      most sleep-related benefits of an intervention combining CBT-I and mindfulness
      meditation were maintained during the 12-month follow-up period, with indications
      that higher presleep arousal and sleep effort at end of treatment constitute a
      risk for occurrence of insomnia during the 12 months following treatment.

PMID- 19114262
TI  - The role of mindfulness in positive reappraisal.
AB  - Mindfulness meditation is increasingly well known for therapeutic efficacy in a
      variety of illnesses and conditions, but its mechanism of action is still under
      debate in scientific circles. In this paper, we propose a hypothetical causal
      model that argues for the role of mindfulness in positive reappraisal coping.
      Positive reappraisal is a critical component of meaning-based coping that enables
      individuals to adapt successfully to stressful life events. Mindfulness, as a
      metacognitive form of awareness, involves the process of decentering, a shifting
      of cognitive sets that enables alternate appraisals of life events. We review the
      concept of positive reappraisal in transactional stress and coping theory, then
      describe research and traditional literature related to mindfulness and positive
      reappraisal, and detail the central role of mindfulness in the reappraisal
      process. With this understanding, we present a causal model explicating the
      proposed mechanism. The discussion has implications for clinical practice,
      suggesting how mindfulness-based integrative medicine interventions can be
      designed to support adaptive coping processes.

PMID- 19114263
TI  - Characteristics of college students enrolled in an alternative
      health/complementary and alternative medicine course: a cross-sectional
      comparison.
AB  - CONTEXT: The rising prevalence of chronic disease in the United States signifies
      a need for innovative health education strategies. One approach would be to
      integrate holistically oriented alternative health content into university health
      education curricula. This would capitalize on growing consumer interest in
      alternative health practices and on the observed relationship between the use of
      alternative health practices and conventional preventive health behaviors.
      OBJECTIVE: The aim of this study was to explore the potential value of
      alternative health curricula. The study was conducted to obtain information on
      demographics, attitudes, and behaviors of students enrolled in a holistic health
      education course. DESIGN: A cross-sectional survey design was employed. SETTING:
      Data was collected at a public university that offers a comprehensive
      undergraduate holistic health curriculum. PARTICIPANTS: Participants were
      undergraduate students fulfilling general education requirements. METHODS: A
      convenience sample of three self-selected groups was surveyed: a holistic health
      education course, a conventional health education course, and a human sexuality
      course. OUTCOME MEASURES: Outcomes included use of alternative
      health/complementary and alternative medicine practices, perceived effects of
      courses on health behaviors, intentions for future employment in a health field,
      and identification with holistic postmodern cultural values. RESULTS: Holistic
      health students were significantly more likely to employ alternative health
      practices and to report identification with holistic cultural values compared
      with the other two groups. Both holistic and conventional health education
      students were significantly more likely to report perceived positive effects of
      courses on health behaviors and intended future employment in a health
      profession. Implications for health promotion and workforce development are
      considered. CONCLUSION: Findings suggest potential benefits of including holistic
      health content in university health education curricula. Replication with a
      larger, representative student sample would be a logical next step.

PMID- 19114264
TI  - Acupuncture for refugees with posttraumatic stress disorder: initial experiences
      establishing a community clinic.

PMID- 19114265
TI  - Status of the state of undernutrition and environmental influences for disease in
      later generations.

PMID- 19114266
TI  - Creating healing organizations.

PMID- 19114267
TI  - Teaching self-care at UCLA Medical School.

PMID- 19114268
TI  - Antepartum high-frequency fetal heart rate sinusoidal rhythm: computerized
      detection and fetal anemia.
AB  - OBJECTIVE: Our aim was to identify antepartum fetal heart rate (FHR) records of
      high-frequency (HF) sinusoidal rhythms from an electronic database (1983-2003)
      and determine clinical outcomes. STUDY DESIGN: At the John Radcliffe Hospital
      (Oxford, UK), 72,297 traces from 19,506 women were analyzed using an algorithm
      that identifies HF sinusoidal rhythms. The case records were reviewed. RESULTS:
      There were 15 (0.21/1000) traces from 8 (0.41/1000) women with an HF sinusoidal
      rhythm. In 5 of 8 women (62.5%), this pattern was associated with fetal anemia
      (hemoglobin < 10.0 g/dL). Their FHR patterns were distinguished from those of the
      other nonanemic fetuses by significantly lower long-term variability. CONCLUSION:
      An antepartum HF sinusoidal rhythm is rare but associated with fetal anemia,
      particularly if it is combined with reduced long-term variability without
      episodes of high FHR variability within 60 minutes. The automated system can
      alert inexperienced staff, who supervise FHR monitoring, by an online warning.

PMID- 19114269
TI  - Eikenella corrodens chorioamnionitis: modes of infection?
AB  - We report a case of preterm labor caused by Eikenella corrodens chorioamnionitis
      at 26 weeks of gestation. The patient and her partner had tongue piercing and had
      daily mutual oral intercourse. Hematogenous spread from repeated trauma to tongue
      piercing and ascending vaginal infection are possible routes for E corrodens
      intraamniotic infection.

PMID- 19114270
TI  - Eosinophil-rich inflammatory response to FloSeal hemostatic matrix presenting as
      postoperative pelvic pain.
AB  - FloSeal hemostatic matrix has been reported to be effective for the control of
      intraoperative bleeding in various surgeries. We report 3 patients who
      experienced a possible allergic response to FloSeal with the formation of
      excessive granulation tissue and fibrosis that were associated with early
      postoperative pelvic pain that led to additional surgical intervention.

PMID- 19114271
TI  - Free T4 immunoassays are flawed during pregnancy.
AB  - OBJECTIVE: The purpose of this study was to evaluate the diagnostic accuracies of
      2 free thyroxine immunoassays during pregnancy. STUDY DESIGN: Serum was collected
      from healthy, thyroid peroxidase antibody-negative women during each trimester
      and nonpregnant controls. Thyrotropin, total T4 (TT4), free T4 index (FT4I), and
      2 different FT4 immunoassays were studied. RESULTS: As expected, TT4 was elevated
      in all 3 trimesters compared to controls (P < .001). FT4I was elevated in the 1st
      trimester as compared with controls (P < .05) and returned to the nonpregnant
      range in the 2nd and 3rd trimesters. In contrast, 1st trimester FT4 immunoassay
      values were either comparable or lower than controls and by the 2nd and 3rd
      trimesters had decreased to approximately 65% of controls. CONCLUSION: Neither
      FT4 immunoassay accurately reflects established free T4 changes during pregnancy.
      TT4 and the FT4I retained an appropriate inverse relationship with TSH throughout
      pregnancy and appear to provide a more reliable free T4 estimate.

PMID- 19114272
TI  - Novel clomiphene "stair-step" protocol reduces time to ovulation in women with
      polycystic ovarian syndrome.
AB  - OBJECTIVE: The objective of the study was to determine the efficacy of a novel
      "stair-step" clomiphene protocol in women with polycystic ovarian syndrome (PCOS)
      who do not respond to 50 mg clomiphene. STUDY DESIGN: This was a retrospective
      analysis at an academic fertility center. The stair-step protocol is performed as
      follows: 50 mg clomiphene for 5 days, ultrasonography on days 11-14. If
      unresponsive, immediately begin 100 mg clomiphene for 5 days and repeat
      ultrasound in 1 week. If still unresponsive, begin 150 mg clomiphene for 5 days
      and repeat the ultrasound in 1 week. Stair-step cycles were compared with
      published historical clomiphene outcomes for women who were nonresponsive.
      RESULTS: The time to ovulation was 32-53 days less with the stair-step protocol
      compared with a traditional regimen. The dose-dependent ovulation rate was 64% at
      100 mg with the stair-step protocol compared with 22% with a traditional regimen.
      CONCLUSION: It is not necessary to induce menses before increasing clomiphene
      doses in nonresponsive PCOS patients.

PMID- 19114273
TI  - Amniotic fluid volume responses to esophageal ligation in fetal sheep:
      contribution of lung liquid.
AB  - OBJECTIVE: The objective of the study was to determine the amniotic fluid volume
      (AFV) response to fetal esophageal ligation with and without fetal lung liquid
      entering the amniotic sac. STUDY DESIGN: AFV was measured in 3 groups of late
      gestation ovine fetuses: time controls, tracheoesophageal shunted, and esophageal
      ligated. RESULTS: One day after surgery, AFV was similar in all groups, averaging
      1064 +/- 66 mL. On postsurgical day 9, AFV was unchanged in control fetuses,
      increased to 3025 +/- 294 mL in fetuses with esophageal ligation and lung liquid
      shunted into the fetal stomach, and to 3437 +/- 430 mL in fetuses with esophageal
      ligation and no shunting. CONCLUSION: AFV expanded gradually following esophageal
      ligation to the highest volume thus far reported in noninfused ovine fetuses.
      Lung liquid entry into the amniotic sac altered neither the time course nor the
      extent of the AFV increase following esophageal ligation.

PMID- 19114274
TI  - Thromboprophylaxis and pregnancy outcomes in asymptomatic women with inherited
      thrombophilias.
AB  - OBJECTIVE: Our objective was to evaluate the effect of thromboprophylaxis on
      pregnancy outcomes in asymptomatic women with inherited thrombophilias. STUDY
      DESIGN: This was a retrospective cohort study of asymptomatic pregnant women with
      inherited thrombophilias. Medical records were reviewed for pregnancy events,
      diagnosis of thrombophilias, and management in subsequent pregnancies. Outcomes
      in women who were and were not treated with thromboprophylaxis were compared
      using Fisher's exact test and logistic regression. RESULTS: Fifty-three women had
      75 pregnancies subsequent to their diagnosis of thrombophilia. Women treated with
      heparin had similar rates of live births (86% vs 82%; P = .8, Fisher's exact
      test) as those not treated. The odds ratio of live birth in all pregnancies for
      women treated with heparin was compared with untreated women and was 1.9 (95%
      confidence interval, 0.5-6.3). CONCLUSION: Pregnancy outcomes are often good in
      asymptomatic women with thrombophilias in the absence of treatment. Treatment of
      these women during pregnancy should be considered investigational.

PMID- 19114275
TI  - Coffee consumption and risk of breast cancer: a metaanalysis.
AB  - OBJECTIVE: This metaanalysis was conducted to assess the association between
      coffee consumption and breast cancer risk. STUDY DESIGN: Relevant studies were
      identified by searching Medline (1966-May 2008) and the reference lists of
      retrieved articles. The summary relative risk (RR) with 95% confidence interval
      (CI) was calculated using a random-effects model. RESULTS: Nine cohort and 9 case
      control studies met the inclusion criteria. The combined RR showed a borderline
      significant influence of highest coffee consumption (RR, 0.95; 95% CI, 0.90-1.00)
      or an increment of 2 cups/day of coffee consumption (RR, 0.98; 95% CI, 0.96-1.00)
      on the risk of breast cancer. In stratified analysis, borderline significant
      associations were observed among cohort and case-control studies and studies
      conducted in Europe and the United States. However, no significant association
      was noted among studies conducted in Asia. CONCLUSION: Our findings suggest a
      possible influence of high coffee consumption or an increased coffee consumption
      on the risk of breast cancer.

PMID- 19114276
TI  - Intervillous and uteroplacental circulation in normal early pregnancy and early
      pregnancy loss assessed by 3-dimensional power Doppler angiography.
AB  - OBJECTIVE: To assess intervillous and uteroplacental circulation in early normal
      pregnancies and miscarriages. STUDY DESIGN: One hundred normal pregnancies and 46
      delayed miscarriages were evaluated by 3-dimensional vaginal ultrasound and power
      Doppler angiography. Volumes of the early placenta and the subplacental area were
      obtained between 5 and 12.6 weeks' gestation. The placental volume,
      vascularization index, flow index, and vascularization flow index was calculated.
      RESULTS: Intraclass correlation coefficients ranged from 0.961 for placental
      volume to 0.885 for intervillous flow index. Intervillous power Doppler signals
      were not detected before the sixth week. Placental volume (R(2) = 0.68),
      intervillous vascularization index (R(2) = 0.30), flow index (R(2) = 0.33) and
      vascularization flow index (R(2) = 0.35), uteroplacental flow index (R(2) =
      0.34), and vascularization flow index (R(2) = 0.17) increase significantly (P <
      .001) throughout the first trimester of normal pregnancies. Uteroplacental
      vascularization index was not significantly related to gestational age.
      Intervillous vasculariztion index, flow index, and vascularization flow index
      were significantly raised in miscarriages, but there were no significant
      differences for uteroplacental vascularization index, flow index, or
      vascularization flow index. CONCLUSION: Intervillous and uteroplacental blood
      flow increases throughout the first trimester of normal pregnancies. Intervillous
      circulation is abnormally increased when a miscarriage is diagnosed.

PMID- 19114278
TI  - The cost-effectiveness of universal screening in pregnancy for subclinical
      hypothyroidism.
AB  - OBJECTIVE: The purpose of this study was to determine whether routine screening
      for subclinical hypothyroidism during pregnancy would be cost-effective. STUDY
      DESIGN: We developed a decision analysis model to compare the cost-effectiveness
      of 2 screening strategies during pregnancy for subclinical hypothyroidism: (1) no
      routine screening of serum thyroid-stimulating hormone (TSH) levels (standard)
      and (2) routine screening of TSH levels. In the latter, women with subclinical
      hypothyroidism received thyroid hormone replacement. We assumed that thyroid
      hormone replacement could reduce the incidence of an offspring IQ < 85 for
      pregnancies with subclinical hypothyroidism. The main outcome measure was
      marginal cost per quality-adjusted life year (QALY) gained. RESULTS: Our model
      predicts that universal screening is the dominant strategy. For every 100,000
      pregnant women who were screened, $8,356,383 are saved, and 589.3 QALYs are
      gained. When subclinical hypothyroidism prevalence is reduced to 0.25%, screening
      remains cost-effective at $21,664/QALY gained. CONCLUSION: Screening for
      subclinical hypothyroidism in pregnancy will be a cost-effective strategy under a
      wide range of circumstances.

PMID- 19114277
TI  - Evidence for participation of uterine natural killer cells in the mechanisms
      responsible for spontaneous preterm labor and delivery.
AB  - OBJECTIVE: The purpose of this study was to determine in a mouse model whether
      uterine natural killer (uNK) cell cytotoxic activation induces
      infection/inflammation-associated preterm labor and delivery. STUDY DESIGN: Wild
      type or interleukin (IL)-10(-/-) mice were injected intraperitoneally with
      lipopolysaccharide on gestational day 14. Mice were either killed for collection
      of uteroplacental tissue, spleen, and serum or allowed to deliver. Uteroplacental
      tissue was used for histology and characterization of uNK cells. RESULTS: Low
      dose lipopolysaccharide treatment triggered preterm labor and delivery in IL-10(
      /-), but not wild type mice, in a manner independent of progesterone levels.
      Preterm labor and delivery in IL-10(-/-) mice was associated with an increased
      number and placental infiltration of cytotoxic uNK cells and placental cell
      death. Depletion of NK cells or tumor necrosis factor (TNF)-alpha neutralization
      in these mice restored term delivery. Furthermore, TNF-alpha neutralization
      prevented uNK cell infiltration and placental cell apoptosis. CONCLUSION: The uNK
      cell-TNF-alpha-IL-10 axis plays an important role in the genesis of
      infection/inflammation-induced preterm labor/delivery.

PMID- 19114279
TI  - Synthesis of water-soluble phthalocyanines bearing four or eight D-galactose
      units.
AB  - The synthesis and structural characterization of two glycophthalocyanines with
      four or eight unprotected D-galactose units is reported. The sugar units are
      linked to the macrocycle via the hydroxyl group located at C-6. The water
      solubility promoted by the carbohydrate moieties provides a potential application
      of these phthalocyanine derivatives as photosensitizers in photodynamic therapy.

PMID- 19114280
TI  - Development of infants' attention to faces during the first year.
AB  - In simple tests of preference, infants as young as newborns prefer faces and face
      like stimuli over distractors. Little is known, however, about the development of
      attention to faces in complex scenes. We recorded eye-movements of 3-, 6-, and 9
      month-old infants and adults during free-viewing of clips from A Charlie Brown
      Christmas (an animated film). The tendency to look at faces increased with age.
      Using novel computational tools, we found that 3-month-olds were less consistent
      (across individuals) in where they looked than were older infants. Moreover,
      younger infants' fixations were best predicted by low-level image salience,
      rather than the locations of faces. Between 3 and 9 months of age, infants
      gradually focused their attention on faces. We discuss several possible
      interpretations of this shift in terms of social development, cross-modal
      integration, and attentional/executive control.

PMID- 19114281
TI  - Pathological features of amyloidosis in stranded California sea lions (Zalophus
      californianus).
AB  - Amyloidosis was diagnosed in 26 stranded adult California sea lions between 1983
      and 2006 by retrospective case analysis. The kidneys (92.3% of animals), blood
      vessels (80.7%) and thyroid glands (65.4%) were most commonly affected.
      Macroscopically, affected kidneys were swollen, with pale tan cortices and loss
      of corticomedullary differentiation. Amyloid deposits in the kidney were located
      in the glomeruli, blood vessels, and peritubular interstitium, most prominently
      in the outer stripe of the medulla. The amyloid deposits were identified as type
      amyloid A (AA) by potassium permanganate staining and immunolabelling with
      antibodies against AA protein. Concurrent diseases, including inflammatory
      processes and genital carcinoma, were common in affected animals. Serum amyloid A
      concentrations were high (>1200 microg/ml) in six of seven affected sea lions,
      while the median value in clinically healthy animals was <10 microg/ml. These
      findings suggest that renal amyloidosis contributes to morbidity and mortality in
      stranded adult California sea lions.

PMID- 19114282
TI  - Redox status and heavy metal risk in intertidal sediments in NW Spain as inferred
      from the degrees of pyritization of iron and trace elements.
AB  - Mariculture is an important economic activity in shallow marine areas of the Rias
      Baixas (Galicia, NW Spain). The maintenance of high product quality requires
      surveillance of environmental quality, including the risk of metal toxicity. In
      this study the redox status of intertidal sediments in the Bay of San Simon, and
      the risk of toxicity posed by their As, Cd, Cr, Cu, Mn, Ni, Pb and Zn contents,
      were evaluated by determination of operationally defined reactive, silicate
      bound, organic and pyrite-related fractions of these elements and of Fe. The
      large silicate-bound fractions of most of these metals indicate their lithogenic
      origin; the main exception is Pb, which in all respects exhibits singular
      behaviour associated with its predominantly anthropogenic origin in a ceramics
      factory. In sediments with larger fine-grained particle contents, which are oxic
      only in the top few centimetres, greater proportions of the trace elements are
      present as sulphides or associated with sulphide minerals: the degree of
      pyritization of Fe (DOP) is 46% overall, and the pyrite fraction of some elements
      doubtless increases at the expense of the reactive fraction, most overall degrees
      of trace metal pyritization (DTMPs) lying in the range 10-50%. A decline in
      pyrite genesis at depths below about 18 cm in these sediments is attributed to
      the exhaustion of organic matter susceptible to metabolization by sulphide
      generating bacteria. In coarse-grained, oxic sediments the oxidation of sulphides
      makes pyrite-related fractions very small, and reactive and silicate-bound
      fractions are negatively correlated; reactive fractions associated with Fe-Mn
      oxyhydroxides are large, and DOP and DTMPs are low (generally much lower than in
      mud-rich sediments), except for Pb. Most of the elements studied are mainly
      present in forms that are neither bioavailable nor potentially bioavailable, and
      so do not constitute a significant environmental threat. However, the high DTMPs
      of Cu and Pb indicate significant potential bioavailability, which should be
      taken into account in evaluations of environmental quality and the risk to
      bivalve cultures.

PMID- 19114283
TI  - Jaagsiekte sheep retrovirus is present at high concentration in lung fluid
      produced by ovine pulmonary adenocarcinoma-affected sheep and can survive for
      several weeks at ambient temperatures.
AB  - Jaagsiekte sheep retrovirus (JSRV) causes a fatal lung cancer of sheep known as
      ovine pulmonary adenocarcinoma (OPA). OPA is a significant disease in many sheep
      rearing countries and there is no effective method of control. A unique feature
      of OPA is the overproduction of fluid in the lung of affected animals. This lung
      fluid contains JSRV and provides a means of transmission through the inhalation
      of virus. In this study we demonstrated that lung fluid from different OPA cases
      contained between 10(7) and 10(10) copies of JSRV RNA per ml. Examination of JSRV
      RNA survival under conditions that mimic natural conditions suggested that intact
      JSRV virions may persist for several weeks in the environment. These are the
      first quantitative data on JSRV in lung fluid and provide valuable information
      for implementing appropriate biosecurity measures to control the spread of JSRV
      in the field.

PMID- 19114284
TI  - Biodegradation potential of pure and mixed bacterial cultures for removal of 4
      nitroaniline from textile dye wastewater.
AB  - Environmentally toxic aromatic amines including nitroanilines are commonly
      generated in dye contaminated wastewater in which azo dyes undergo degradation
      under anaerobic conditions. The aim of this study was to develop a process for
      biological treatment of 4-nitroaniline. Three bacteria identified as
      Acinetobacter sp., Citrobacter freundii and Klebsiella oxytoca were isolated from
      enrichment cultures of activated sludge on 4-nitroaniline, after which the
      isolates and the mixed culture were studied to determine optimal conditions for
      biodegradation. HPLC analyses showed the mixed culture was capable of complete
      removal of 100micromol/L of 4-nitroaniline within 72h under aerobic conditions.
      There was an inverse linear relationship (R(2)=0.96) between the rate of
      degradation (V) and 4-nitraoaniline concentrations [S] over 100-1000micromol/L.
      The bacterial culture was also capable of decolorizing structurally different azo
      dyes (Acid Red-88, Reactive Black-5, Direct Red-81, and Disperse Orange-3) and
      also degraded nitrobenzene. Our findings show that enrichment cultures from
      activated sludge can be effective for the removal of dyes and their toxic
      intermediates, and that treatment may best be accomplished using an anaerobic
      aerobic process.

PMID- 19114285
TI  - Sensitivity of macroinvertebrates to carbendazim under semi-field conditions in
      Thailand: implications for the use of temperate toxicity data in a tropical risk
      assessment of fungicides.
AB  - The present paper discusses the fate of the fungicide carbendazim (nominal
      concentrations: 0, 3.3, 33, 100 and 1000 microg L(-1)) and its effects on the
      macroinvertebrate community in outdoor microcosms set up in Thailand. Fate and
      threshold values were subsequently compared with those noted in temperate model
      ecosystem studies in order to evaluate to which extent toxicity data generated in
      temperate regions for compounds like carbendazim may be extrapolated to tropical
      areas. Carbendazim disappeared faster from the water column than reported in
      temperate model ecosystem studies, which is explained by a possibly greater
      microbial breakdown of the fungicide under the tropical conditions tested. The No
      Observed Effect Concentration (NOEC) calculated in the present study for the
      macroinvertebrate community was the same as recorded in a study carried out in
      The Netherlands (3.3 microg L(-1)). However, most sensitive representatives in
      the latter study were "worm-like" taxa, whereas water boatmen (Corixidae) were
      the most sensitive macroinvertebrates in the present study. The ecological
      realism of a tropical risk assessment based on temperate organisms that are less
      sensitive than local macroinvertebrates may be questionable. Recommendations for
      future research include testing the possibility to rear sensitive representatives
      of indigenous Thai Corixidae in the laboratory and conducting model ecosystem
      studies evaluating a wider range of pesticides on a larger tropical geographical
      scale.

PMID- 19114286
TI  - Comparative studies on the biospeciation of antidiabetic VO(IV) and Zn(II)
      complexes.
AB  - The speciation of several insulin-mimetic/enhancing VO(IV) and Zn(II) complexes
      in human blood serum was studied and a comparison was made concerning the ability
      of the serum components to interact with the original metal complexes and the
      distribution of the metal ions between the low and the high molecular fractions
      of the serum. It was found that the low molecular mass components may play a
      larger role in transporting Zn(II) than in the case with VO(IV). Among the high
      molecular mass serum proteins, transferrin is the primary binder of VO(IV), and
      albumin is that of Zn(II). The results revealed that protein-ligand interactions
      may influence the metal ion distribution in the serum.

PMID- 19114287
TI  - Structure and dynamics of a DNA-based model system for the study of electron spin
      spin interactions.
AB  - We report on the structure and dynamics of a model system for measuring long
      range distances in biological macromolecules by saturation-recovery EPR. Four DNA
      duplexes that incorporate a paramagnetic dysprosium ion (Dy(III)) and a nitroxide
      spin-label were examined by electron paramagnetic resonance (EPR), circular
      dichroism (CD), and ultra-violet absorbance (UV) spectroscopy. Dy(III) is
      chelated by the modified base deoxythymidine-EDTA, (dT-EDTA). Electron spin-spin
      interactions between the Dy(III) ion and the nitroxide radical are observed at
      distances as great as approximately 5.3 nm. A slight change in the conformation
      of those nucleotides lying between the EDTA(Dy(III)) complex and the nitroxide
      spin-label results in a "stiffening" of the DNA helix on the EPR time scale.
      Changes in conformation and helix dynamics are due to the binding of the
      EDTA(Dy(III)) complex to the phosphodiester backbone of the complementary strand.
      Molecular mechanics calculations indicate that binding occurs in the 5' direction
      on the complementary strand, at a position 3 or 4 phosphates distant from the dT
      EDTA(Dy(III))*dA base pair.

PMID- 19114288
TI  - Probabilistic distribution coefficients (K(d)s) in freshwater for radioisotopes
      of Ag, Am, Ba, Be, Ce, Co, Cs, I, Mn, Pu, Ra, Ru, Sb, Sr and Th: implications for
      uncertainty analysis of models simulating the transport of radionuclides in
      rivers.
AB  - The objective of this study was to provide operational probability density
      functions (PDFs) for distribution coefficients (K(d)s) in freshwater,
      representing the partition of radionuclides between the particulate and the
      dissolved phases respectively. Accordingly, the K(d) variability should be
      considered in uncertainty analysis of transport and risk assessment models. The
      construction of PDFs for 8 elements (Ag, Am, Co, Cs, I, Mn, Pu and Sr) was
      established according to the procedure already tested in Durrieu et al. [2006. A
      weighted bootstrap method for the determination of probability density functions
      of freshwater distribution coefficients (K(d)s) of Co, Cs, Sr and I
      radioisotopes. Chemosphere 65 (8), 1308-1320]: (i) construction of a
      comprehensive database where K(d)s values obtained under various environments and
      parametric conditions were collected; (ii) scoring procedure to account for the
      'quality' of each datapoint (according to several criteria such as the
      presentation of data (e.g. raw data vs mean with or without replicates), contact
      time, pH, solid-to-liquid ratio, expert judgement) in the construction of the
      PDF; (iii) weighted bootstrapping procedure to build the PDFs, in order to give
      more importance to the most relevant datapoints. Two types of PDFs were
      constructed: (i) non-conditional, usable when no knowledge about the site of
      concern is available; (ii) conditional PDFs corresponding to a limited range of
      parameters such as pH or contact time; conditional PDFs can thus be used when
      some parametric information is known on the site under study. For 7 other
      radionuclides (Ba, Be, Ce, Ra, Ru, Sb and Th), a simplified procedure was adopted
      because of the scarcity of data: only non-conditional PDFs were built, without
      incorporating a scoring procedure.

PMID- 19114289
TI  - Adsorption and transformation of selected human-used macrolide antibacterial
      agents with iron(III) and manganese(IV) oxides.
AB  - The adsorption/transformation of two members (clarithromycin and roxithromycin)
      of the macrolide (ML) antibacterial agents on the surface of three environmental
      subsurface sorbents (clay, iron(III) and manganese(IV) oxy-hydroxides) was
      investigated. The adsorption fitted well to the Freundlich model with a high
      sorption capacity. Adsorption probably occurred through a surface complexation
      mechanism and was accompanied by slow degradation of the selected MLs.
      Transformation proceeded through two parallel pathways: a major pathway was the
      hydrolysis of the cladinose sugar, and to a lesser extent the hydrolysis of the
      lactone ring. A minor pathway was the N-dealkylation of the amino sugar. This
      study indicates that Fe(III) and Mn(IV) oxy-hydroxides in aquatic sediments may
      play an important role in the natural attenuation of MLs. Such an attenuation
      route yields a range of intermediates that might retain some of their biological
      activity.

PMID- 19114290
TI  - Lifespan changes in working memory in fragile X premutation males.
AB  - Fragile X syndrome is the world's most common hereditary cause of developmental
      delay in males and is now well characterized at the biological, brain and
      cognitive levels. The disorder is caused by the silencing of a single gene on the
      X chromosome, the FMR1 gene. The premutation (carrier) status, however, is less
      well documented but has an emerging literature that highlights a more subtle
      profile of executive cognitive deficiencies that mirror those reported in fully
      affected males. Rarely, however, has the issue of age-related declines in
      cognitive performance in premutation males been addressed. In the present study,
      we focus specifically on the cognitive domain of working memory and its
      subcomponents (verbal, spatial and central executive memory) and explore
      performance across a broad sample of premutation males aged 18-69 years matched
      on age and IQ to unaffected comparison males. We further tease apart the
      premutation status into those males with symptoms of the newly identified
      neurodegenerative disorder, the fragile X-associated tremor/ataxia syndrome
      (FXTAS) and those males currently symptom-free. Our findings indicate a specific
      vulnerability in premutation males on tasks that require simultaneous
      manipulation and storage of new information, so-called executive control of
      memory. Furthermore, this vulnerability appears to exist regardless of the
      presence of FXTAS symptoms. Males with FXTAS symptoms demonstrated a more general
      impairment encompassing phonological working memory in addition to central
      executive working memory. Among asymptomatic premutation males, we observed the
      novel finding of a relationship between increased CGG repeat size and impairment
      to central executive working memory.

PMID- 19114291
TI  - Optimization of the continuous biosorption of copper with sugar-beet pectin gels.
AB  - Sugar-beet pectin xerogels obtained from residues of the sugar industry are an
      adequate material for metal recovery from effluents in continuous systems. The
      xerogels were used as a biosorbent for copper removal in a fixed-bed column. The
      performance of the system was evaluated in different experimental conditions:
      flow rate, bed height, inlet metal concentration and feeding system (drop and
      reverse). The effect on the biosorption parameters (saturation time, amount of
      adsorbed and treated metal, column performance and metal uptake) and the shape of
      the breakthrough curves was determined. The saturation time increased with
      increasing bed height but decreased with increasing feed flow rate and inlet
      metal concentration. Preferential flow channels greatly influenced the metal
      uptake and column performance. Copper was completely desorbed with 0.1M HNO(3).
      Additionally, the column data fitted both the linear and nonlinear expressions of
      the Thomas model.

PMID- 19114292
TI  - A dynamic hydrological Monte Carlo simulation model to inform decision-making at
      Lake Toolibin, Western Australia.
AB  - Lake Toolibin, an ephemeral lake in the agricultural zone of Western Australia,
      is under threat from secondary salinity due to land clearance throughout the
      catchment. The lake is extensively covered with native vegetation and is a Ramsar
      listed wetland, being one of the few remaining significant migratory bird
      habitats in the region. Currently, inflow with salinity greater than 1000 mg/L
      TDS is diverted from the lake in an effort to protect sensitive lakebed
      vegetation. However, this conservative threshold compromises the frequency and
      extent of lake inundation, which is essential for bird breeding. It is speculated
      that relaxing the threshold to 5000 mg/L may pose negligible additional risk to
      the condition of lakebed vegetation. To characterise the magnitude of improvement
      in the provision of bird breeding habitat that might be generated by relaxing the
      threshold, a dynamic water and salt balance model of the lake was developed and
      implemented using Monte Carlo simulation. Results from best estimate model inputs
      indicate that relaxation of the threshold increases the likelihood of satisfying
      habitat requirements by a factor of 9.7. A second-order Monte Carlo analysis
      incorporating incertitude generated plausible bounds of [2.6, 37.5] around the
      best estimate for the relative likelihood of satisfying habitat requirements.
      Parameter-specific sensitivity analyses suggest the availability of habitat is
      most sensitive to pan evaporation, lower than expected inflow volume, and higher
      than expected inflow salt concentration. The characterisation of uncertainty
      associated with environmental variation and incertitude allows managers to make
      informed risk-weighted decisions.

PMID- 19114293
TI  - Identification of brain- and bone-specific breast cancer metastasis genes.
AB  - In breast cancer, metastases are relatively widely distributed, with the most
      common sites being bone, regional lymph nodes, lung, liver, and brain. The
      detailed mechanism of organ-specific metastasis is poorly understood. In this
      study, we initiated a search for genes that are implicated in brain or bone
      metastasis of primary human breast cancer. We generated gene expression profiles
      of 18 brain and eight bone metastases derived from primary breast tumors. We
      identified 73 genes differentially expressed between brain and bone metastases.
      Visualization of the differential gene expression profiles by correspondence and
      cluster analyses shows that the metastases clearly separate into two distinct
      groups as an exact reflection of their site of metastasis. Moreover, the analysis
      of this gene set in primary breast tumors relapsing to either bone or brain
      allowed accurate categorization of the tumors according to their metastatic site.
      The identified genes may prove to be excellent markers to predict the site of
      metastasis in breast cancer patients and could lead to tailor-made therapy to an
      individual patient.

PMID- 19114294
TI  - Enhancing daily functioning with exposure and acceptance strategies: an important
      stride in the development of psychological therapies for pediatric chronic pain.

PMID- 19114296
TI  - When a mouth is a wound.

PMID- 19114297
TI  - Efficacy of buccal midazolam compared to intravenous diazepam in controlling
      convulsions in children: a randomized controlled trial.
AB  - A study was done to examine the efficacy of buccal midazolam in controlling
      convulsion in children by comparing it with intravenous diazepam, a standard mode
      of treating convulsions. One hundred and twenty cases presenting with convulsions
      to emergency were treated randomly with either buccal midazolam (in a dose of
      0.2mg/kg) or intravenous diazepam (in a dose of 0.3mg/kg). Partial seizures,
      generalized tonic, clonic and tonic-clonic convulsions were included irrespective
      of duration or cause. One episode per child only was included. The frequency of
      overall control of convulsive episodes within 5 min were 85% and 93.3% in buccal
      midazolam and intravenous diazepam groups, respectively; the difference was,
      however, not statistically significant (p=0.142). The mean time needed for
      controlling the convulsive episodes after administration of the drugs was
      significantly less with intravenous diazepam (p=<0.001). The mean time for
      initiation of treatment was significantly less with buccal midazolam (p=<0.001).
      The mean time for controlling the convulsive episodes after noticing these first
      were significantly less with buccal midazolam than with intravenous diazepam
      (p=0.004) that is likely to be due to longer time needed for initiating treatment
      with intravenous diazepam in preparing the injection and establishing an IV line.
      There was no significant side effect in both the groups. The findings suggest
      that buccal midazolam can be used as an alternative to intravenous diazepam
      especially when getting an IV line becomes difficult. In situations where
      establishing an IV line is a problem, buccal midazolam may be the first choice.

PMID- 19114295
TI  - Differential effects of the cannabinoid receptor agonist, WIN 55,212-2, on lamina
      I and lamina V spinal trigeminal nucleus caudalis neurons.
AB  - Direct application of cannabinoids to the medullary dorsal horn (MDH) inhibits
      lamina V nociceptive neurons. The present study compared the effect of the
      cannabinoid receptor agonist, WIN 55,212-2 (WIN-2) on the activity of lamina I
      and lamina V MDH neurons using extracellular single unit recording in
      anesthetized rats. Activity evoked by a contact thermode was measured before and
      after local application of WIN-2 (0.5-2.0 microg/microl) to the brainstem. Fast
      and slow heat ramps were used to differentiate between activity evoked primarily
      by A-delta and C primary afferent fibers, respectively. In lamina V neurons, WIN
      2 produced a concentration dependent decrease in activity evoked by both fast and
      slow heat, reaching significance at 1.0 microg/microl. In lamina I neurons, WIN-2
      administration inhibited slow heat-evoked activity beginning at 1.0
      microg/microl, but had no significant effect on fast heat-evoked activity, even
      at the highest concentration (2.0 microg/microl). In separate experiments, the
      effect of intrathecal administration of WIN-2 to the MDH on head withdrawal
      latencies elicited by fast and slow heat ramps applied to the whisker pad was
      assessed in lightly anesthetized rats. Head withdrawal latencies elicited by slow
      but not by fast heat stimulation were increased by WIN-2. Taken together, these
      results emphasize the importance of lamina I neurons in the control of a
      nociceptive heat-evoked reflex.

PMID- 19114298
TI  - Serum and cerebrospinal fluid levels of cytokines in acute encephalopathy
      associated with human herpesvirus-6 infection.
AB  - Human herpesvirus-6 (HHV-6) is a causative agent of exanthema subitum. The
      immunological pathogenesis of acute encephalopathy associated with HHV-6
      infection is still unclear. We measured the concentrations of interferon-gamma
      (IFN-gamma), tumor necrosis factor-alpha (TNF-alpha), interleukin-2 (IL-2), IL-4,
      IL-6, IL-10, and soluble TNF receptor 1 (sTNFR1) in serum and cerebrospinal fluid
      (CSF) during the acute stage in 15 infants with acute encephalopathy and 12 with
      febrile seizures associated with HHV-6 infection. The serum IL-6, IL-10, sTNFR1,
      CSF IL-6, and sTNFR1 levels of infants with encephalopathy who had neurological
      sequelae (n=9) were significantly higher than those with febrile seizures
      (p=0.011, 0.043, 0.002, 0.029, and 0.005, respectively). In acute encephalopathy,
      serum IL-6, sTNFR1, and CSF IL-6 levels in infants with neurological sequelae
      were significantly higher than those without (n=6) neurological sequelae
      (p=0.043, 0.026, and 0.029, respectively), and serum IFN-gamma, IL-6, IL-10, and
      sTNFR1 levels were significantly higher than those in the CSF (p=0.037, 0.037,
      0.001, and 0.021, respectively). There were no significant differences in serum
      or CSF cytokine levels between infants who were positive for HHV-6 DNA in the CSF
      (n=6) compared to those who were negative (n=9). We suggest that cytokines
      mediate the pathogenesis of acute encephalopathy associated with HHV-6 infection,
      and that the elevated levels of serum IL-6, sTNFR1, and CSF IL-6 are important
      for predicting neurological sequelae.

PMID- 19114299
TI  - The levels of telomere-binding proteins in human tumours and therapeutic
      implications.
AB  - Tumours require telomeric integrity to maintain viability, conferred by adequate
      length of telomeric DNA replenished by telomerase, and binding of telomere
      binding proteins (TBPs), thus telomeres have received attention as an anticancer
      target. Levels of TBPs in tumour tissue may have implications for drug
      development if they render some cancers relatively more sensitive or resistant to
      telomere targeted agents. This review gives an overview of the studies examining
      the levels of TBPs in tumours and discusses possible reasons for differences in
      the findings, given the interplay between various factors determining telomere
      stability. Whether cancers with lower levels of TBPs will be more susceptible to
      therapies targeting telomere maintenance will require clinical trials of these
      novel therapies.

PMID- 19114301
TI  - Urological applications of N.O.T.E.S.
AB  - While adrenal and kidney urological surgery has been performed in animal models
      mainly by transvesical accesses, to date, NOTES in humans remains in an
      investigational and developmental phase. Despite great experimental interest, no
      specific devices are currently available for urological indications in humans and
      therefore several instruments, taken from different specialist fields, have been
      used to access through the different natural orifices (including transgastric,
      transcolonic, transvaginal and transvesical approaches). Furthermore, the
      accumulating experience with the transvesical approach to the peritoneum suggests
      it presents new challenges for urologists in terms of technical demands. For
      these reasons, given their competition with the success of laparoscopy and
      minimally invasive techniques, NOTES applications in urology risk being
      underevaluated. In our opinion, after the initial enthusiastic phase, NOTES will
      cover only specific indications for urological conditions. The transvesical
      approach to the peritoneum however seems to be one of the best approaches for
      NOTES overall and certainly the most promising for urologists.

PMID- 19114300
TI  - Phase I clinical and pharmacokinetic study of trabectedin and doxorubicin in
      advanced soft tissue sarcoma and breast cancer.
AB  - The combination of trabectedin (T) and doxorubicin (D) was brought into clinical
      development in soft tissue sarcoma (STS) and advanced breast cancer (ABC) because
      of its in vitro and in vivo additive anti-tumour effect, the fact that there are
      no overlapping toxicities and the anti-tumour activity of T in those tumours.
      Feasibility and anti-tumour activity of T+D administered every 3 weeks were
      evaluated in 38 patients (STS=29, ABC=9) untreated for advanced disease. D was
      given at 60 mg/m(2) and T at escalating doses from 600 to 800 microg/m(2), which
      was the maximum tolerated dose due to dose-limiting febrile neutropenia and
      asthenia. The recommended dose--given to 18 patients in total--was 700
      microg/m(2) T with 60 mg/m(2) D. The pharmacokinetic profile of T and D at cycle
      1 was analysed in 20 patients. The most common toxicities included a severe but
      reversible ASAT/ALAT increase (94%), nausea/vomiting, neutropenia,
      asthenia/fatigue, stomatitis. Partial response and stable disease were assessed
      in 18% and 56% of STS patients and in 55% and 33% of ABC patients. No
      pharmacokinetic interaction between T and D was observed. The lack of cumulative
      toxicity and related complications and the promising activity in STS support
      further development of T+D.

PMID- 19114302
TI  - Thermodynamic and kinetic studies for environmentaly friendly Ni(II) biosorption
      using waste pomace of olive oil factory.
AB  - The objective of this study is to assess the environmentaly friendly Ni(II)
      adsorption from synthetic wastewater using waste pomace of olive oil factory
      (WPOOF). Batch kinetic studies were performed in order to investigate the
      adsorbent and adsorbate dose, solution pH, agitating speed and temperature. The
      maximum Ni(II) adsorption was obtained at pH 4.0. The equilibrium nature of
      Ni(II) adsorption at different temperature was described by the Freundlich,
      Langmuir and Temkin isotherms. The equilibrium data fit well the Temkin and
      Langmuir isotherm. The monolayer adsorption capacities of WPOOF as obtained from
      Langmuir isotherm at 60 degrees C was found to be 14.80 mg/g. The adsorption
      mechanism was examined by the FTIR technique. The results of the thermodynamic
      investigations indicated that the adsorption reactions were spontaneous (DeltaG <
      0), slightly endothermic (DeltaH > 0) and irreversible (DeltaS > 0). The pseudo
      first-order, pseudo second-order, Elovich and intraparticle diffusion kinetic
      models were used to describe the kinetic data.

PMID- 19114303
TI  - Use of Saccharum spontaneum (wild sugarcane) as biomaterial for cell
      immobilization and modulated ethanol production by thermotolerant Saccharomyces
      cerevisiae VS3.
AB  - Saccharum spontaneum is a wasteland weed consists of 45.10+/-0.35% cellulose and
      22.75+/-0.28% of hemicellulose on dry solid (DS) basis. Aqueous ammonia
      delignified S. spontaneum yielded total reducing sugars, 53.91+/-0.44 g/L
      (539.10+/-0.55 mg/g of substrate) with a hydrolytic efficiency of 77.85+/-0.45%.
      The enzymes required for hydrolysis were prepared from culture supernatants of
      Aspergillus oryzae MTCC 1846. A maximum of 0.85+/-0.07 IU/mL of filter paperase
      (FPase), 1.25+/-0.04 IU/mL of carboxy methyl cellulase (CMCase) and 55.56+/-0.52
      IU/mL of xylanase activity was obtained after 7 days of incubation at 28+/-0.5
      degrees C using delignified S. spontaneum as carbon source under submerged
      fermentation conditions. Enzymatic hydrolysate of S. spontaneum was then tested
      for ethanol production under batch and repeated batch production system using "in
      situ" entrapped Saccharomyces cerevisiae VS3 cells in S. spontaneum stalks (1 cm
      x 1 cm) size. Immobilization was confirmed by the scanning electron microscopy
      (SEM). Batch fermentation of VS3 free cells and immobilized cells showed ethanol
      production, 19.45+/-0.55 g/L (yield, 0.410+/-0.010 g/g) and 21.66+/-0.62 g/L
      (yield, 0.434+/-0.021 g/g), respectively. Immobilized VS3 cells showed maximum
      ethanol production (22.85+/-0.44 g/L, yield, 0.45+/-0.04 g/g) up to 8th cycle
      during repeated batch fermentation followed by a gradual reduction in subsequent
      cycles of fermentation.

PMID- 19114304
TI  - SAR and biological evaluation of analogues of a small molecule histone
      deacetylase inhibitor N-(2-aminophenyl)-4-((4-(pyridin-3-yl)pyrimidin-2
      ylamino)methyl)benzamide (MGCD0103).
AB  - Analogues of the clinical compound MGCD0103 (A) were designed and synthesized.
      These compounds inhibit recombinant human HDAC1 with IC(50) values in the sub
      micromolar range. In human cancer cells growing in culture these compounds induce
      hyperacetylation of histones, cause expression of the tumor suppressor protein
      p21(WAF1/CIP1), and inhibit cellular proliferation. Lead molecule of the series,
      compound 25 is metabolically stable, possesses favorable pharmacokinetic
      characteristics and is orally active in vivo in different mouse tumor xenograft
      models.

PMID- 19114305
TI  - 3-amido-4-anilinoquinolines as CSF-1R kinase inhibitors 2: Optimization of the PK
      profile.
AB  - The optimization of compounds from the 3-amido-4-anilinoquinolines series of CSF
      1R kinase inhibitors is described. The series has excellent activity and kinase
      selectivity. Excellent physical properties and rodent PK profiles were achieved
      through the introduction of cyclic amines at the quinoline 6-position. Compounds
      with good activity in a mouse PD model measuring inhibition of pCSF-1R were
      identified.

PMID- 19114306
TI  - Small-molecule perturbation of competing interactions between c-Myc and Max.
AB  - The oncogenic transcription factor c-Myc undergoes coupled binding and folding of
      its basic-helix-loop-helix-leucine zipper domain (bHLHZip) upon
      heterodimerization with its partner protein Max. The latter exists in two
      isoforms: p21, which homodimerizes poorly, and p22, which homodimerizes well. We
      show that the effect of 10058-F4 (a small-molecule that binds disordered c-Myc
      monomers and disrupts the c-Myc-Max complex) on both c-Myc-Max heterodimerization
      and DNA binding is dependent on the nature of the Max isoform. In the presence of
      p22 Max the effective inhibitor concentration is lower than in the presence of
      p21 Max, as the p22 Max homodimer formation affects the thermodynamics by
      competing against the c-Myc-Max heterodimerization event.

PMID- 19114307
TI  - Spiro-piperidine azetidinones as potent TRPV1 antagonists.
AB  - A series of spiro-piperidine azetidinone were synthesized and evaluated as
      potential TRPV1 antagonists. An important issue of plasma stability was
      investigated and resolved. Further focused SAR study lead to the discovery of a
      potent antagonist with good oral pharmacokinetic profile in rat.

PMID- 19114308
TI  - Ivermectin-derived leishmanicidal compounds.
AB  - In the present study a family of macrocyclic and acyclic analogues as well as
      seco-analogues of avermectins were prepared from commercial Ivermectin (IVM) and
      their antileishmanial activity assayed against axenic promastigote and
      intracellular amastigote forms of Leishmania amazonensis. Contrarily to the
      filaricidal activity, the leishmanicidal potentiality of avermectin analogues
      does not appear to depend on the integrity of the non-conjugated Delta(3,4)
      hexahydrobenzofuran moiety. Conjugated Delta(2,3)-IVM or its corresponding
      conjugated secoester show higher anti-leishmania activity than the parent
      compound. Surprisingly, the diglycosylated northern sub-unit exhibits the same
      anti-amastigote potentiality as the southern hexahydrobenzofuran. As expected for
      compounds derived from the widely used Ivermectin antibiotic, little toxicity has
      been noticed for most of the novel analogues prepared.

PMID- 19114309
TI  - A TOPological Sub-structural Molecular Design (TOPS-MODE)-QSAR approach for
      modeling the antiproliferative activity against murine leukemia tumor cell line
      (L1210).
AB  - Lately, Quantitative Structure-Activity Relationship (QSAR) studies have been
      afar used to predict anticancer activity taking into account different molecular
      descriptors, statistical techniques, cell lines and data set of congeneric and
      non-congeneric compounds. Herein we report a QSAR study based on a TOPological
      Sub-structural Molecular Design (TOPS-MODE) approach, aiming at predicting the
      anticancer leukemia activity of a diverse data set of indolocarbazoles
      derivatives. Finally, several aspects of the structural activity relationships
      are discussed in terms of the contribution of different bonds to the anticancer
      activity, thereby making the relationship between structure and biological
      activity more transparent.

PMID- 19114310
TI  - Bisubstrate Inhibitors of the MYST HATs Esa1 and Tip60.
AB  - Esa1 (essential Sas2-related acetyltransferase 1) and Tip60 (HIV-1 TAT
      interactive protein, 60 kDa) are key members of the MYST family of histone
      acetyltransferases (HATs) and play important functions in many cellular
      processes. In this work, we designed, synthesized and evaluated a series of
      substrate-based analogs for the inhibition of Esa1 and Tip60. The structures of
      these analogs feature that coenzyme A is covalently linked to the side chain
      amino group of the acetyl lysine residues in the histone peptide substrates.
      These bisubstrate analogs exhibit stronger potency in the inhibition of Esa1 and
      Tip60 compared to the small molecules curcumin and anacardic acid. In particular,
      H4K16CoA was tested as one of the most potent inhibitors for both Esa1 and Tip60.
      These substrate-based analog inhibitors will be useful mechanistic tools for
      analyzing biochemical mechanisms of Esa1 and Tip60, defining their functional
      roles in particular biological pathways, and facilitating protein crystallization
      and structural determination.

PMID- 19114311
TI  - Photoreactivity of biologically active compounds. XIX: excited states and free
      radicals from the antimalarial drug primaquine.
AB  - The formation and reactivity of excited states and free radicals from primaquine,
      a drug used in the treatment of malaria, was studied in order to evaluate the
      primary photochemical reaction mechanisms. The excited primaquine triplet was not
      detected, but is likely to be formed with a short lifetime (<50 ns) and with a
      triplet energy <250 kJ/mol as the drug is an efficient quencher of the fenbufen
      triplet and the biphenyl triplet, and forms (1)O(2) by laser flash photolysis
      ((PQ)Phi(Delta)=0.025). Primaquine (PQ) exists as the monocation (PQH(+)) in
      aqueous solution at physiological pH. PQH(+) photoionises by a biphotonic process
      and also forms the monoprotonated cation radical (PQH(2+)*) by one electron
      oxidation by HO* (k(q)=6.6 x 10(9) M(-1) s(-1)) and Br*(2)(-) (k(q)=4.7 x 10(9)
      M(-1) s(-1)) at physiological pH, detected as a long-lived transient decaying
      essentially by a second order process (k(2)=7.4 x 10(8) M(-1) s(-1)). PQH(2+)* is
      scavenged by O(2), although at a limited rate (k(q)=1.0 x 10(6) M(-1) s(-1)). The
      reduction potential (E degrees) of PQH(2+)*/PQH(+) is < +1015 mV, as measured
      versus tryptophan (TRP*/TRPH). Primaquine also forms PQH(2+)* at pH 2.4, by one
      electron oxidation by Br*(2)(-) and proton loss (k(q)=2.7 x 10(9) M(-1) s(-1)).
      The non-protonated cation radical (PQ(+)*) is formed during one electron
      oxidation with Br*(2)(-) at alkaline conditions (k(q)=4.2 x 10(9) M(-1) s(-1) at
      pH 10.8). The estimated pK(a)-value of PQH(2+)*/PQ(+)* is pK(a) approximately 7
      8. Primaquine is not a scavenger of O*(2)(-) at physiological pH. Thus self
      sensitization by O*(2)(-) is eliminated as a degradation pathway in the
      photochemical reactions. Impurities in the raw material and photochemical
      degradation products initiate photosensitized degradation of primaquine in
      deuterium oxide, prevented by addition of the (1)O(2) quencher sodium azide.
      Photosensitized degradation by formation of (1)O(2) is thus important for the
      initial photochemical decomposition of primaquine, which also proceeds by free
      radical reactions. Formation of PQH(2+)* is expected to play an essential part in
      the photochemical degradation process in a neutral, aqueous medium.

PMID- 19114312
TI  - Cellular and histopathological changes in the infrapatellar fat pad in the
      monoiodoacetate model of osteoarthritis pain.
AB  - OBJECTIVE: The infrapatellar fat pad (IPFP) has been identified as a source of
      anterior knee pain. Fibrosis and marked inflammatory infiltrate in the IPFP of
      patients with arthritis of the knee and reduction in pain post knee replacement
      in patients following resection of the IPFP have been observed. We have
      investigated changes in the IPFP of rats undergoing the monoiodoacetate (MIA)
      model of degenerative joint disease, a model that exhibits some histopathological
      similarities to osteoarthritis (OA). METHODS: Rats were injected intra
      articularly with MIA and the development of weight bearing asymmetry was followed
      for 21 days as compared to vehicle-injected animals. In addition, IPFPs were
      removed from both ipsilateral and contralateral joints. Both inflammatory
      infiltrate and histopathological changes were analysed. RESULTS: MIA injection
      caused marked weight bearing asymmetry. Ipsilateral IPFP wet weights were
      significantly increased on days 1 and 3 in MIA-treated animals. MIA treatment
      also resulted in significant increases in IPFP total white blood cells and
      monocytes on days 1, 3, and 7 and neutrophils on days 1 and 3. This was supported
      by histopathological findings at early time points which progressed to adipocyte
      necrosis, IPFP fibrosis, patellar cartilage and subchondral bone necrosis with
      synovial hyperplasia at later timepoints. CONCLUSIONS: The current study clearly
      demonstrated that marked inflammatory changes in the IPFP occur during the early
      stage of the MIA model of OA which may contribute to the pain observed at this
      early stage. The role of the IPFP in later stages of the model needs to be
      further explored.

PMID- 19114313
TI  - In vitro determination of biomechanical properties of human articular cartilage
      in osteoarthritis using multi-parametric MRI.
AB  - The objective of this study was to evaluate the correlations between MR
      parameters and the biomechanical properties of naturally degenerated human
      articular cartilage. Human cartilage explants from the femoral condyles of
      patients who underwent total knee replacement were evaluated on a micro-imaging
      system at 3T. To quantify glycosaminoglycan (GAG) content, delayed gadolinium
      enhanced MRI of the cartilage (dGEMRIC) was used. T(2) maps were created by using
      multi-echo, multi-slice spin echo sequences with six echoes: 15, 30, 45, 60, 75,
      and 90 ms. Data for apparent diffusion constant (ADC) maps were obtained from
      pulsed gradient spin echo (PGSE) sequences with five b-values: 10.472, 220.0,
      627.0, 452.8, 724.5, and 957.7. MR parameters were correlated with mechanical
      parameters (instantaneous (I) and equilibrium (Eq) modulus and relaxation time
      (tau)), and the OA stage of each cartilage specimen was determined by
      histological evaluation of hematoxylin-eosin stained slices. For some parameters,
      a high correlation was found: the correlation of T(1Gd) vs Eq (r=0.8095), T(1Gd)
      vs I/Eq (r=-0.8441) and T(1Gd) vs tau (r=0.8469). The correlation of T(2) and ADC
      with selected biomechanical parameters was not statistically significant. In
      conclusion, GAG content measured by dGEMRIC is highly related to the selected
      biomechanical properties of naturally degenerated articular cartilage. In
      contrast, T(2) and ADC were unable to estimate these properties. The results of
      the study imply that some MR parameters can non-invasively predict the
      biomechanical properties of degenerated articular cartilage.

PMID- 19114315
TI  - Calcium phosphate-based particles influence osteogenic maturation of human
      mesenchymal stem cells.
AB  - Biphasic calcium phosphates (BCPs) consist of a mixture of hydroxyapatite and
      beta-tricalcium phosphate and are recommended as alternatives or additives to
      autogenous bone for orthopaedic and dental applications. There is clinical
      evidence showing particle release from bioceramics, which might impair the
      ability of human mesenchymal stem cells (hMSC) from bone marrow to proliferate or
      mature into a functional osteoblast phenotype. This study analyses the influence
      of BCP particles and their precursors, calcium-deficient apatite (CDA) particles,
      on in vitro hMSC behaviour. Both types of particles were efficiently internalized
      by hMSC. Cell viability, morphology and actin cytoskeleton reorganization were
      unaffected by exposure of hMSC to BCP or CDA particles. Direct exposure to BCP
      particles impaired hMSC osteogenic differentiation and bone matrix mineralization
      to a lesser extent than CDA, as assayed by evaluation of alkaline phosphatase
      activity, osteopontin secretion and mineralized nodule formation. The ability of
      bioceramic particles to affect osteogenic maturation through modification of
      soluble factors in media was assayed in an in vitro system that avoids direct
      cell-particle contact. Indirect exposure to CDA particles severely impaired hMSC
      osteogenic maturation owing to the uptake of Ca2+ from the culture media. Lower
      textural properties of BCP and the lack of calcium deficiency in its composition
      prevented Ca2+ uptake, allowing the development of a functional osteoblast
      phenotype.

PMID- 19114314
TI  - Direct measurements of protein backbone 15N spin relaxation rates from peak line
      width using a fully-relaxed Accordion 3D HNCO experiment.
AB  - Protein backbone (15)N spin relaxation rates measured by solution NMR provide
      useful dynamic information with a site-specific resolution. The conventional
      method is to record a series of 2D (1)H-(15)N HSQC spectra with varied relaxation
      delays, and derive relaxation rate from the following curve fitting on the
      resonance intensities. Proteins with poorly resolved spectra often require
      several 3D HNCO spectra to be collected on a (15)N/(13)C double labeled protein
      sample. In order to reduce the relaxation dimension Carr et al. (P.A. Carr, D.A.
      Fearing, A.G. Palmer, 3D accordion spectroscopy for measuring N-15 and (CO)
      Carbon-13 relaxation rates in poorly resolved NMR spectra, J. Magn. Reson. 132
      (1998) 25-33) employed an Accordion type HNCO pulse sequence to obtain (15)N or
      (13)C T(1) relaxation rates by numerical fitting of the relaxation interfered
      free induction decay (FID) data. To avoid intensive analysis of the time domain
      data, we propose a modified protocol to measure (15)N T(1) and T(2) relaxation
      rates from easily obtained line-widths in an Accordion HNCO spectrum. Both T(1)
      and T(2) relaxation could be simultaneously convoluted into the constant-time
      evolution periods of (13)C' and (15)N, respectively. The relaxation delay was
      allowed to reach at least 3 x T(1) or 3 x T(2) so that the signal was
      substantially decayed by the end of the FID, and the resulting peak full-width at
      half height (FWHH) could be directly used to calculate relaxation rate. When
      applied to the 76-residue Ubiquitin and the 226-residue glutamine-binding protein
      (GlnBP), this method yielded T(1) and T(2) values deviating on average by 4-6%
      and 5-7%, respectively, from the measurements based on the conventional 2D
      method. In comparison, the conventional methods possessed intrinsic error ranges
      of 2-4% for T(1) and 3-6% for T(2). In addition to comparable accuracy, the fully
      relaxed Accordion HNCO method presented here allowed measurements of relaxation
      rates for resonances unresolved in 2D spectra, thus providing a more complete
      dynamic picture of the protein.

PMID- 19114316
TI  - Production of morphology-controllable porous hyaluronic acid particles using a
      spray-drying method.
AB  - Hyaluronic acid (HA) porous particles with controllable porosity and pore size,
      ranging from 100 to 300 nm, were successfully prepared using a colloidal
      templating and spray-drying method. HA powder and polystyrene latex (PSL)
      particles, which were used as the precursor and templating agent, respectively,
      were mixed in aqueous solution and spray-dried using a two-fluid nozzle system to
      produce HA and PSL composite particles. Water was evaporated during spray-drying
      using heated air with a temperature of 120 degrees C. This simple process was
      completed within several seconds. The prepared particles were collected and
      washed with an organic solvent to dissolve the PSL templating agent. The porosity
      and pore size of the resulting particles were easily controlled by changing the
      initial mass ratio of precursor to templating agent, i.e., HA to PSL, and by
      altering the size of the PSL template particles.

PMID- 19114317
TI  - Breast sarcoma--a review of diagnosis and management.
AB  - Sarcoma of the breast is a rare condition. The biological differences from other
      primary breast tumours necessitate a corresponding difference in approach to
      diagnostic and management strategies. The rarity of the condition has made
      clinicopathological study difficult, with most series limited to less than 50
      patients. We review the current literature on the diagnosis and management of
      breast sarcoma, and highlight areas of likely future development.

PMID- 19114318
TI  - Surveillance of surgical site infections after thyroidectomy in a one-day surgery
      setting.
AB  - BACKGROUND AND AIM: Different studies underline the importance of hospital stay
      on the development of infectious complications. We performed an audit of surgical
      site infections (SSI) after thyroidectomy was performed in a one-day surgery
      setting. MATERIALS AND METHODS: One hundred and twelve consecutive patients
      admitted between April 2007 and discharged before May 2008 were studied. Patient
      selection criteria for one-day surgery were specific medical and social-logistic
      status. The technique of thyroidectomy was standardized. RESULTS: SSI affect 2.6%
      of patients undergoing thyroid surgery with short hospitalization. The incidence
      of SSI was 3.2% following thyroidectomy, 2% for lobectomy. Mean time interval to
      symptom onset was 3 days (range 2-6). Most likely organism was Staphylococcus
      aureus. WI was associated with prolonged ambulatory medications. CONCLUSIONS:
      Rates of SSI are similar to those described in the literature with longer
      hospitalization. All SSI become evident only after patient discharge. Prevention
      of SSI is very much the responsibility of the persons working in the operating
      theater. Effort should be made to improve sterile technique. Appropriate
      antibiotic coverage is indicated when infection develops postoperatively.

PMID- 19114319
TI  - Skinning clitorectomy and skin replacement in women with vulvar intra-epithelial
      neoplasia.
AB  - BACKGROUND AND AIM: Partial or total clitoris amputation for vulvar intra
      epithelial neoplasia (VIN) affects quality of life and sexual function and is
      likely to constitute over-treatment as superficial excision of only the involved,
      thinly cornified, stratified squamous clitoral epithelium would suffice. For this
      reason, we applied skinning clitorectomy and replacement of clitoral skin as an
      organ-sparing surgical therapy for clitoral VIN. METHODS: Seven consecutive
      patients presenting with VIN were treated from July 2003 to February 2008. The
      skin of the glans clitoridis was resected from the underlying spongious tissue by
      combined hydro-dissection and sharp dissection. The spongiosum was subsequently
      covered with either a thin skin flap from the inner aspect of the remaining
      preputium or minor labium, or a split-thickness skin graft taken from the
      proximal inner aspect of the thigh. RESULTS: In all patients, the preoperative
      diagnosis of VIN was confirmed histopathologically. Additionally, micro-invasive
      carcinoma was found in two. The postoperative course was complicated by haematoma
      in one patient and a superficial infection in another, but these did not
      influence the overall satisfactory outcome obtained in all patients. Preoperative
      sexual function was largely preserved and, after a mean follow-up of 21 months,
      no recurrence or invasion of the original lesion was observed in any of the
      patients. CONCLUSION: We advocate skinning clitorectomy and replacement of its
      skin as a sound organ-sparing alternative for clitoral amputation in the
      treatment of clitoral VIN.

PMID- 19114320
TI  - Venous malformations of the limbs: the Birmingham experience, comparisons and
      classification in children.
AB  - The management of vascular anomalies in upper and lower limbs is complex. The
      current practice at Birmingham Children's Hospital is based on a
      multidisciplinary approach, involving plastic surgeons, interventional
      radiologists, vascular surgeons, dermatologists and laser specialists. This study
      reviews the management strategies for peripheral venous malformations (VMs) and
      proposes a simple classification system to aid treatment. A retrospective review
      was undertaken involving all paediatric patients presenting with (VMs) of the
      upper and lower limbs, managed by the same multidisciplinary team over a period
      of 3 years. A total of 33 patients were identified, of whom 19 had lesions
      located in the upper limb. Treatment modalities included surgery, sclerotherapy,
      a combination of the two and conservative management. The indications for
      treatment included: (1) worsening pain, (2) increased swelling, (3) reduced
      function, (4) bleeding or ulceration and finally, (5) cosmetic deformity.
      Following treatment, outcome measures with regards to the symptoms were graded
      into (1) improved, (2) worsened and (3) unchanged. Based on magnetic resonance
      imaging, we were able to apply our classification to separate the lesions into
      Type 1a (superficial localised): nine, Type 1b (superficial diffused): five, Type
      2 (Fascia/muscle infiltration): nine, Type 3 (Bone/joint infiltration): seven and
      Type 4 (Extensive whole-limb infiltration): three. In patients with upper limb
      VMs (n=19), eight lesions (42%) were superficial and localised (Type 1a) while
      the rest were diffused lesions. In contrast, in the lower limb (n=14), only one
      lesion (7%) was superficial while the rest were diffused lesions. Lower success
      rate for treatment was noted in lower limb malformations (p<0.05). In eight
      patients with recurrence of symptoms, six had Type 3 (intra-articular) lesions.
      There was one major and three minor complications following treatment. An outline
      of the management strategies for VMs in peripheral limbs is discussed in this
      article. An anatomical classification is described which aids in management and
      communication.

PMID- 19114321
TI  - C-reactive protein is not a reliable marker of infection in flap reconstructive
      procedures of lower extremities.

PMID- 19114322
TI  - Tissue engineering and auricular reconstruction: a review.
AB  - This article provides an up-to-date review of the strategies used in auricular
      cartilage engineering. The currently available options in stem cell, biomaterial
      and bio-molecules and the crucial issues for the auricular cartilage engineering
      are presented. Researchers have demonstrated that neo-cartilage can be
      constituted in a predetermined shape and in complex three-dimensional structures,
      such as a human ear, by using cell transplantation on polymer constructs. Despite
      this, many unsolved problems still remain. No perfect materials and methods have
      been found to substitute the shapely elastic cartilage normally present in the
      ear, and the current constructs have not proven to be durable over time. The
      recent advances in surgical techniques and biotechnology can promise clinical
      application of bio-engineered cultured cartilage in the future. Further long-term
      in vitro and in vivo studies must be done before tissue engineering can be
      applied to reconstructive surgery of the auricle.

PMID- 19114323
TI  - Pyogenic liver abscess associated with septic pulmonary embolism.

PMID- 19114324
TI  - Effect of somatostatin in the prevention of pancreatic complications after
      endoscopic retrograde cholangiopancreatography.
AB  - BACKGROUND: The unique clinical role of endoscopic retrograde
      cholangiopancreatography (ERCP) in diagnosing and treating biliary tree diseases
      cannot be completely replaced by other modern imaging modalities such as magnetic
      resonance cholangiopancreatography. However, post-ERCP pancreatitis is one of the
      most common and life-threatening complications. Prophylactic medication in the
      prevention of pancreatitis during ERCP is still controversial. The objective of
      the present study was to investigate the role of different regimens of
      somatostatin in the prevention of acute pancreatitis after ERCP and analyze the
      risk factors contributing to post-ERCP complications. METHODS: From July 1999 to
      September 2000, 133 patients with benign biliary disease who received ERCP for
      diagnosis or treatment were enrolled. Group A patients received a bolus of
      somatostatin infusion before ERCP, followed by continuous infusion for 12 hours.
      Group B patients received a bolus of somatostatin before ERCP only, and group C
      patients were the controls who did not receive somatostatin treatment. Serum
      amylase levels before and 24 hours after ERCP, and abdominal pain were recorded.
      RESULTS: There were no significant differences in bile duct and pancreatic duct
      visualization, ratio of diagnostic and therapeutic ERCP, procedure time, post
      procedural hyperamylasemia and pancreatitis among the 3 groups. For patients with
      visualization of the pancreatic duct, the incidences of hyperamylasemia (serum
      amylase > or = 220 U/L) were higher than in patients without visualization of the
      pancreatic duct (p < 0.001). All 6 patients with post-ERCP pancreatitis had
      pancreatic duct visualization, and recovered after conservative treatment.
      CONCLUSION: Continuous infusion of somatostatin after ERCP does not seem to be
      helpful in the prevention of pancreatic complications after ERCP. Pancreatic duct
      visualization is a risk factor for pancreatic complications.

PMID- 19114325
TI  - Mechanical characterization of rabbit pulmonary vein sleeves in in vitro intact
      ring preparation.
AB  - BACKGROUND: Pulmonary vein (PV) sleeves, composed of cardiomyocytes, play certain
      roles in arrhythmogenesis. In the literature, it has been frequently reported
      that PV sleeves possess intrinsic spontaneous pacemaking activity and triggered
      activity in normal dogs and rabbits. In contrast, other research groups presented
      totally opposite findings which showed absence of such pacemakers in dogs,
      rabbits and rats. The present study was designed to clarify this puzzle and
      contradiction. METHODS: A novel methodology using in vitro experimentation was
      used to examine the electromechanical activity of whole segments of PV sleeves.
      The ring preparation was composed of a small piece of left atrial (LA) free wall,
      PV ostium and sleeve from rabbits. A circumferential contraction of the PV sleeve
      was measured when the preparation was electrically driven from the LA free wall.
      Mechanical force of the ring preparation was measured using a force transducer.
      The action potentials were recorded using conventional intracellular recording
      technique in strip preparation. RESULTS: In 15 rabbits, no spontaneous pacemaking
      activity or triggered activity was found in the in vitro ring preparation of PV
      sleeve. The circumferential contraction of PV sleeves was external calcium
      dependent. Frequency-force relation displayed a negative staircase at 0.1-0.5 Hz
      and a positive staircase at 1-5 Hz. Post-rest potentiation was prominent between
      15 s and 120 s. Intracellular action potential recording did not display any
      automaticity or triggered activity in PV sleeves. CONCLUSION: In an intact ring
      preparation of rabbit PV sleeves, intrinsic spontaneous pacemaking activity or
      triggered activity was not found.

PMID- 19114326
TI  - Community-based study on summer-winter difference in insulin resistance in Kin
      Chen, Kinmen, Taiwan.
AB  - BACKGROUND: The aim of this community-based study was to explore the summer
      winter difference in insulin resistance in Kin-Chen, Kinmen. METHODS: A total of
      2,412 residents aged 40 and over was enrolled in a mass survey in Kin-Chen,
      Kinmen, by the Yang-Ming Crusade, a volunteer organization of well-trained
      medical students from National Yang-Ming University. All participants were
      investigated in winter (first phase, January and February, before Chinese New
      Year) and summer (secondary phase, July and August) in 2002. Structured
      questionnaires, demographic and physical data, lifestyle, and blood chemistry
      parameters were collected. RESULTS: Higher levels of fasting insulin, HOMA
      insulin resistance and triglycerides, but lower levels of high-density
      lipoprotein cholesterol were found in summer than in winter. The prevalence of
      metabolic syndrome was higher in summer than in winter, with differences of 7.7%
      in both genders (p = 0.0092 in men, p = 0.0037 in women). Body mass index (BMI),
      age and physical activity were significantly correlated with metabolic syndrome.
      After controlling for BMI and other risk profiles, summer was independently and
      positively associated with fasting insulin and insulin resistance regardless of
      metabolic syndrome. CONCLUSION: Fasting insulin, insulin resistance and
      prevalence of metabolic syndrome were higher in summer than in winter. BMI and
      season were 2 major determinants of the variation in fasting insulin. The
      contextual impacts of seasonal variation in shaping metabolic syndrome or insulin
      resistance in populations need to be reemphasized.

PMID- 19114327
TI  - Expression analysis of apoptosis-related markers TP53, BCL-2, BAX and c-MYC in
      female genital tract sarcomas.
AB  - BACKGROUND: Most female genital tract sarcomas are highly malignant and fatal.
      Their aggressive growth pattern and poor response to chemotherapy are the major
      causes of death. Deregulation of the apoptosis pathway is related to
      tumorigenesis and chemodrug resistance. The purpose of this study was to
      investigate the expression status and relationship of the apoptosis-related
      markers TP53, BCL-2, BAX and c-MYC in this group of tumors. In addition,
      correlations of these markers with clinicopathologic findings and their
      prognostic significance were also examined. METHODS: Paraffin blocks of female
      genital tract sarcoma tissue from 54 patients were obtained after pathology
      review. Protein expression of TP53, BCL-2, BAX and c-MYC was examined using
      immunohistochemical staining with standard procedures. A semiquantitative method
      was used to assess the staining result where scoring 1-3 was negative and 4-9 was
      positive for expression. The mutual relationships between TP53, BCL-2, BAX and c
      MYC were examined. Associations between expression of the apoptotic markers and
      tumor stage as well as outcome were also analyzed. RESULTS: We found that all 4
      of the apoptosis-related markers were frequently expressed in female genital
      tract sarcomas. Of the 54 cases, 24 (44%) were positive for TP53, 23 (43%) for
      BCL-2, 25 (46%) for BAX, and 30 (56%) for c-MYC. A significant positive
      association was observed between BAX and c-MYC (p < 0.001). There was no
      significant difference for the expression status of the 4 markers in early and
      late stage tumors. In prognostic analysis, overexpression of TP53, late stage,
      and age were significant prognostic factors in both univariate and multivariate
      analyses. CONCLUSION: Since changes in TP53, BCL-2, BAX and c-MYC frequently
      occur in female genital tract sarcomas, deregulation of apoptosis appears to be
      involved in the pathogenesis of this group of tumors. This mechanism may occur
      early in tumorigenesis and include the c-MYC/BAX apoptotic pathway or BCL-2.
      However, TP53 mutation may play a crucial role in this process, and clinically,
      it could be used as a prognostic indicator.

PMID- 19114328
TI  - Esophageal food impaction: a homemade suction tube attached to
      esophagogastroduodenoscopy for food bolus removal.
AB  - The most common esophageal foreign body in adults is impacted food bolus.
      Polypectomy snares, Dormia baskets, retrieval nets, rat-tooth forceps, alligator
      forceps or polyp graspers are usually used to remove it. Here, we report the case
      of a 78-year-old woman whose esophagogastroduodenoscopy (EGD) showed a firm goose
      liver impacted tightly in the lower esophagus; all of the above-mentioned
      retrieval instruments could not remove it. We used a homemade device by attaching
      a modified nasogastric tube to an EGD and successfully removed the goose liver by
      suction under endoscopic visualization. The method is very effective to remove
      firm and tightly impacted materials in a narrow lumen. When the usual retrieval
      instruments fail, a homemade suction tube attached to an EGD is an alternative.

PMID- 19114329
TI  - Alveolar rhabdomyosarcoma of the left hand with bilateral breast metastases in an
      adolescent female.
AB  - Rhabdomyosarcoma is a common extramammary malignancy in pediatric age groups, but
      it rarely metastasizes to the breast. Breast rhabdomyosarcomas are commonly
      metastatic, with possible primary locations at the head and neck, trunk,
      extremities, retroperitoneum and perianal region. We report a case of primary
      alveolar rhabdomyosarcoma of the upper extremities in a 17-year-old adolescent
      female who presented with bilateral lower limb weakness and bilateral breast
      lumps.

PMID- 19114330
TI  - Xanthogranulomatous pyelonephritis successfully treated with antibiotics only.
AB  - A 73-year-old woman with leukemia presented with urinary tract infection, splenic
      abscess, and a renal mass. Both urine culture and pus culture of the splenic
      abscess yielded Klebsiella pneumoniae. Percutaneous biopsy of the renal mass
      confirmed the diagnosis of xanthogranulomatous pyelonephritis. Because of high
      risk for surgery, the patient received treatment with antibiotic therapy for 2
      months. With antibiotic therapy, not only was the splenic abscess cured but
      follow-up ultrasonography also showed progressive resolution of the renal mass.
      Xanthogranulomatous pyelonephritis is frequently associated with urinary tract
      obstruction or nephrolithiasis. In this first report of xanthogranulomatous
      pyelonephritis in a patient with leukemia and splenic abscess, we provide a short
      review of xanthogranulomatous pyelonephritis successfully treated with
      antibiotics only.

PMID- 19114331
TI  - Lymphoma presenting as peritoneal lymphomatosis with ascites.
AB  - Multiple intra-abdominal organ infiltration or disseminated peritoneal lymphoma
      receives much less attention than peritoneal carcinomatosis in clinical practice.
      This may be due to its relatively infrequent occurrence. In this report, an 89
      year-old woman was diagnosed with disseminated peritoneal lymphoma with gastric
      and rectal involvement and marked ascites. Flow cytometry of the surface markers
      for ascites showed positive results for CD19, CD20 and CD45. Biopsy of the
      stomach and rectum were all reported to show diffuse large B-cell lymphoma. The
      cytology of ascites is a simple and effective method for making a diagnosis from
      adequate samples with time limitations. The management of this disease depends on
      the individual case. It must be kept in mind that differential diagnosis from
      other pathologic entities with similar imaging features or high ascitic fluid
      adenosine deaminase levels is difficult because of considerable overlap of
      clinical features. To prolong the survival of patients with peritoneal
      lymphomatosis, diagnosis should be made as early as possible.

PMID- 19114332
TI  - Congenital arteriovenous fistula with aneurysm formation of ulnar artery origin.
AB  - Naturally formed arteriovenous fistula (AVF) causing local vascular aneurysm
      dilatation in the forearm ulnar artery region is rare and is exceedingly uncommon
      in any age group. Presented is a case of AVF in the left ulnar artery of a 39
      year-old man in whom there was no history of trauma; the deformity had been noted
      since childhood. The AVF had become tortuous and enlarged in size as the patient
      aged. As a result, aneurysm dilatation formed on the base of the AVF and that of
      the ulnar artery origin. Despite normal preoperative Allen test result and normal
      preoperative finger pressure measurement with ulnar artery occlusion, arterial
      duplex imaging showed that the radial artery was the dominant artery of the left
      arm; the AVF was resected and the base of the aneurismal dilatation, which was
      directly related to the ulnar artery, was repaired for the sake of the natural
      continuity of ulnar blood flow.

PMID- 19114333
TI  - [Self-adapted segmentation of pulmonary nodule based on region growing].
AB  - OBJECTIVE: To improve the accuracy and efficiency of pulmonary nodule
      segmentation of thoracic CT image for computer-aided diagnostic (CAD) system,
      especially for those nodules adhering to the pleural or blood vessels. METHODS:
      We proposed the automatic process of pulmonary nodule segmentation, and using
      region growing method based on the contrast and gradient, the pulmonary nodule
      images were acquired. A self-adapted morphologic segmentation algorithm was
      presented for the unsuccessful nodule segmentation using region growing. RESULTS
      AND CONCLUSIONS: Experiments on clinical 2D pulmonary images showed that the
      solitary pulmonary nodules and those adhering to the pleural or blood vessels
      could all be segmented. This pulmonary nodule segmentation algorithm is feasible
      for automated segmentation of the thoracic CT images.

PMID- 19114334
TI  - [Construction and expression of RU486-inducible eukaryotic vector carrying red
      fluorescent protein].
AB  - OBJECTIVE: To construct an inducible eukaryotic vector carrying red fluorescent
      protein (DsRed) and evaluate the regulation of DsRed gene expression in vitro.
      METHODS: The vector pRS17-RUDsRed containing DsRed gene, promoter and RU486
      inducible system was constructed using molecular biological methods. To minimize
      potential interference, the two transcriptional elements were spaced with a 1.6
      kb insulator. Fluorescence microscopy and flow cytometry were used to observe the
      activation of this regulatable vector after transfection in MFC cells. RESULTS:
      The vector was identified by digestion with different restriction enzymes,
      sequencing and PCR. In the absence of RU486, the cells transfected with the
      vector exhibited very low DsRed protein expression, and the addition of RU486
      induced efficient DsRed expression in the cells. CONCLUSION: The RU486-inducible
      eukaryotic vector carrying DsRed protein allows effective regulation of the
      target gene expression in vitro, which provides a useful tool for gene regulation
      and gene therapy studies.

PMID- 19114335
TI  - [Effect of selenium and zinc on the proliferation of human esophageal cancer
      Eca109 cell line in vitro].
AB  - OBJECTIVE: To observe the effect of selenium and zinc alone or in combination on
      the growth and proliferation of human esophageal cancer Eca109 cell line in
      vitro. METHODS: Different doses of sodium selenite and zinc sulfate were added
      into the culture medium of Eca109 cells and normal liver epithelial HL7702 cells
      (control), and the changes in the cell growth were assessed by means of cell
      growth curve, (3)H-thymidine incorporation assay and flow cytometry. RESULTS:
      High-concentration selenium (0.3 micro g/ml) and zinc (3.5 microg/ml) alone both
      obviously inhibited Eca109 cell proliferation, and the inhibitory effect was
      enhanced by a combined treatment. At high concentrations, both selenium and zinc
      promoted HL7702 cell proliferation, but when combined, they produced inhibitory
      effect on the cell growth. Selenium and zinc at the physiological concentrations
      ( 0.1 microg/ml and 1.0 microg/ml, respectively) produced similar effects on
      Eca109 cells and the control cells. Selenium at 0.3 microg/ml caused Eca109 cell
      growth arrest in S phase, but this effect was not statistically significant; 3.5
      microg/ml zinc significantly increased the number of Eca109 cells in G(1) phase.
      When combined, 0.3 microg/ml selenium and 3.5 microg/ml zinc caused significant
      G(1) arrest and promoted apoptosis of the cancer cells, an effect stronger than
      that of either of the agents used alone. CONCLUSION: High-concentration selenium
      and zinc show a synergetic effect in inducing growth inhibition of human
      esophageal cancer Eca109 cell line possibly by causing cell cycle arrest and
      promoting cell apoptosis, and their combined use can be toxic to normal human
      liver epithelial cells.

PMID- 19114336
TI  - [Strychnos alkaloids inhibit the proliferation of adult rat neuroprogenitor
      cells].
AB  - OBJECTIVE: To study the effects of strychnos alkaloids on the proliferation of
      adult rat neuroprogenitor cells. METHODS: Strychnos alkaloids free of strychnine
      and brucine were extracted from Strychnos nux vomica, and the effects of
      Strychnos alkaloids on the survival of HEK293 and PC12 cells were evaluated using
      MTT assay. In vitro cultured adult rat neuroprogenitor cells isolated from the
      hippocampus were treated with different concentrations of Strychnos alkaloids for
      2 days, and the cell proliferation was assessed using BrdU incorporation assay.
      RESULTS: At the concentration above 0.5 mg/ml, Strychnos alkaloids produced toxic
      effect against HEK293 cells (P<0.0001), while for PC12 cells, Strychnos alkaloids
      inhibited the cell survival at the concentration as low as 5 microg/ml
      (P<0.0001). After 2 days of exposure to 50 microg/ml Strychnos alkaloids, the
      neuroprogenitor cells showed significantly decreased number of BrdU-positive
      cells (P<0.01), but the total cell number remained stable when compared with that
      of the control cells (P>0.05), whereas at the concentration of 100 microg/ml,
      Strychnos alkaloids produced obvious cytotoxicity against the neuroprogenitor
      cells. CONCLUSION: Strychnos alkaloids can significantly inhibit the
      proliferation of adult rat neuroprogenitor cells, and this effect is probably
      selective, suggesting the potential of Strychnos alkaloids as a new drug for
      treatment of neurocytoma.

PMID- 19114337
TI  - [Programmed application of extracellular matrix promotes neural differentiation
      of mouse embryonic stem cells].
AB  - OBJECTIVE: To study the role of extracellular matrix (ECM) in neural
      differentiation of mouse embryonic stem cells (ESCs). METHODS: Mouse ESCs were
      incubated in the ESC conditioned medium, and the formation of embryonic bodies
      (EBs) were induced in bacteriological dishes using high-concentration all-trans
      retinoic acid (RA). The EBs were seeded on different matrixes (gelatin,
      fibronectin, and laminin/poly-L-ornithine) to test their impact on neural
      differentiation of the ESCs using immunofluorescence assay. The effect of
      laminin/poly-L-ornithine on the growth of neurites was evaluated with
      fluorescence microscopy. RESULTS: High-concentration RA activated and accelerated
      the differentiation of ESCs toward nestin-positive neural progenitor cells.
      Fibronectin supplement in the matrix dose-dependently promoted ESC
      differentiation into neural progenitor cells, while laminin/poly-L-ornithine
      increased the growth of the neurites and induced the maturation of the
      differentiated neural cells. CONCLUSION: ECM plays an important role in neural
      differentiation of mouse ESCs, and application of FN produces the most
      conspicuous effect during the differentiation of the ESCs into the neural
      progenitor cells;laminin/poly-L-ornithine is the most effective during their
      differentiation into neural cells.

PMID- 19114338
TI  - [Effect of Tongxinluo on nestin and vascular endothehal growth factor mRNA
      expression in rat brain tissue after cerebral ischemia-reperfusion injury].
AB  - OBJECTIVE: To investigate the expressions of nestin and vascular endothehal
      growth factor (VEGF) mRNAs in rat brain tissue after cerebral ischemia
      reperfusion injury and their changes in response to Tongxinluo (a traditional
      Chinese herbal preparation) treatment. METHODS: Cerebral ischemia was induced in
      rats by temporary middle cerebral artery occlusion (MCAO) followed by treatment
      with Tongxinluo at high and low doses. On days 3, 7, 14 and 21 after MCAO, nestin
      and VEGF mRNA expressions in the ependyma, subventricular zone (SVZ), and
      hippocampal subdentate gyrus zone (HDG) in the ischemic hemisphere were
      quantitatively analyzed using immunohistochemistry and RT-PCR. RESULTS: Compared
      with the sham-operated group, the rats with cerebral ischemia-reperfusion injury
      showed significantly increased nestin-positive neurons and VEGF mRNA expression
      in the SVZ and HDG 7, 14 and 21 days after MCAO (P<0.05). Treatment with
      Tongxinluo, especially at high doses, significantly increased the number of
      nestin-positive neurons and VEGF mRNA expression in the rats 7, 14 and 21 days
      after MCAO (P<0.05). CONCLUSION: Focal cerebral ischemia in rats results in rapid
      response and proliferation of neural stem cells in the SVZ and HDG in the
      ischemic hemisphere possibly by increasing VEGF mRNA expression in the adjacent
      tissues around the ischemic focus. Tongxinluo may enhance the differentiation and
      proliferation capacity of the neural stem cells after MCAO by inducing the
      expression of VEGF mRNA.

PMID- 19114339
TI  - [Construction of a recombinant adenovirus vector harboring human transforming
      growth factor-beta type II receptor-IgG1Fc fusion gene].
AB  - OBJECTIVE: To construct a recombinant adenoviral vector harboring human
      transforming growth factor-beta type II receptor-IgG1Fc (TbetaRII-IgG1Fc) fusion
      gene. METHODS: The cDNA fragments of human TbetaRII and IgG1Fc genes were
      amplified by RT-PCR and fused with overlap PCR to obtain the fusion gene TbetaRKK
      IgG1Fc. The TbetaRII-IgG1Fc gene was cloned into the shuttle plasmid pAdTrack
      CMV, which was linearized and transfected into E.coli BJ 5183 strain containing
      the adenoviral backbone vector. The recombinant adenovirus vector was constructed
      by homologous recombination. The recombinant adenoviral plasmid was linearized
      and transfected into 293 cells, followed by amplification and purification of the
      virus and detection of TbetaRII-IgG1Fc mRNA expression by RT-PCR. The functional
      activity of the recombinant adenoviral plasmid was assessed using enzyme-linked
      immunosorbent assay (ELISA). RESULTS: The results of restriction endonuclease
      digestion and DNA sequencing indicated correct sequence of the target TbetaRII
      IgG1Fc fusion gene. The recombinant adenoviral plasmid expressed hTbetaRII-IgG1Fc
      and neutralized TGF-beta1 in vitro after infection of the human lung fibroblasts
      (HLF), as confirmed by RT-PCR and ELISA. CONCLUSIONS: The recombinant adenoviral
      plasmid capable of neutralizing TGF-beta1 in vitro is constructed successfully.

PMID- 19114340
TI  - [Role of Ca2+/calmodulin-dependent calcineurin signaling pathway in neuropeptide
      Y-induced cardiac hypertrophy in rats].
AB  - OBJECTIVE: To investigate the role of Ca(2+)/calmodulin-dependent calcineurin
      (CaN) signaling pathway in neuropeptide Y (NPY)-induced cardiomyocyte hypertrophy
      in rat. METHODS: Cardiomyocytes of neonatal Wistar rats were cultured in the
      presence of 10 and 100 nmol/L NPY, and cyclosporine A (CsA) was applied to
      inhibit the activity of CaN. The protein synthesis rate, c-jun mRNA expression,
      CaN protein expression, CaN activity and intracellular Ca(2+) concentration in
      the cardiomyocytes were assessed. RESULTS: Compared with the control group, (3)H
      Leu incorporation and expression of c-jun mRNA in the cardiomyocytes treated with
      100 nmol/L NPY increased significantly (P<0.05, P<0.001), and the effect of NPY
      was blocked by CsA. The activity of CaN (P<0.05), CaN expression (P<0.05), and
      Ca(2+) concentration in the cytoplasm (P<0.001) and nuclei (P<0.001) of the cells
      with 100 nmol/L NPY treatment also significantly increased compared with those in
      the control cells. CONCLUSION: NPY can induce cardiomyocyte hypertrophy in rats,
      in which process Ca(2+)/calmodulin-dependent CaN signaling pathway plays an
      important role.

PMID- 19114341
TI  - [Glycine is involved in the modulation of respiratory rhythmical discharge
      activity in neonatal rat medullary brain slices].
AB  - OBJECTIVE: To determine the role of glycine (Gly) in the generation and
      modulation of basic respiratory rhythm. METHODS: Neonatal (0-3 days) SD rats of
      either sex were used in this study. The medulla oblongata brain slice containing
      the medial region of the nucleus retrofacialis (mNRF) and the hypoglossal nerve
      rootlets was prepared, and the surgical procedure was performed in the modified
      Kreb's solution (MKS) with continuous carbogen (95% O(2) and 5% CO(2)) within 3
      min. The rhythmical respiratory discharge activity (RRDA) of the hypoglossal
      nerve rootlets was recorded using suction electrode. Eighteen medulla oblongata
      slice preparations were divided into 3 groups and treated for 20 min with Gly
      receptor specific agonist Gly (10 micromol/L), Gly receptor antagonist strychnine
      (STR, 1 micromol/L), or Gly+STR after a 20 min Gly application. The changes in
      RRDA of the hypoglossal nerve rootlets were observed. RESULTS: Gly significantly
      decreased the inspiratory time and integral amplitude (IA), but the changes of
      respiratory cycle (RC) and expiratory time (TE) were not statistically
      significant. STR induced a decrease in expiratory time and respiratory cycle
      without significantly affecting the inspiratory time or integral amplitud. The
      effect of Gly on the respiratory rhythm was partially reversed by additional
      application of STR. CONCLUSION: Gly may play an important role in the modulation
      of RRDA in the medulla oblongata slice of neonatal rats.

PMID- 19114342
TI  - [rAAV/BA46-transfected dendritic cells can induce specific cellular immunity].
AB  - OBJECTIVE: To study the feasibility of transfecting breast cancer BA46 gene into
      dendritic cells (DCs) using adeno-associated virus (AAV) to induce specific
      cellular immunity. METHODS: Mononuclear cells (DC precursor) were isolated from
      the peripheral blood of healthy donors by density gradient centrifugation and
      infected with rAAV/BA46/Neo virus stock (transfection group) or pulsed with 293
      cell lysate (control group). In both groups, maturation of the DC precursor was
      induced by granulocyte-macrophage colony-stimulating factor (GM-CSF), interleukin
      4 (IL-4) and tumor necrosis factor-alpha(TNF-alpha). On day 7, the DCs were
      collected and mixed with T cells at the ratio of 1 to 20 to induce cytotoxic T
      lymphocytes (CTL). The capacity of the DCs in stimulating T lymphocyte
      proliferation was assessed using (3)H-thymidine incorporation assay. The
      expressions of interferon-gamma (IFN-gamma), IL-4, CD4, CD8, CD25 and CD69 in the
      CTLs were analyzed with cytometry, and the cytotoxicity of the CTLs was evaluated
      with (51)Cr-release assay using BA46-positive breast cancer cell line Hs578T as
      the target. RESULTS: The DCs transfected with BA46 gene exhibited potent capacity
      to stimulate T lymphocyte proliferation. The CTL population induced by the
      transfected DCs expressed high levels of CD8, CD69 and IFN-gamma, and showed
      strong cytotoxicity against BA46-positive breast cancer cell line Hs578T, which
      was BA46 antigen-specific and MHC-limited. CONCLUSION: The success in BA46 gene
      transfer in the DCs that induce specific cellular immunity provides the
      experimental basis for breast cancer immunotherapy using genetically modified
      cells.

PMID- 19114343
TI  - [Expression of TRPM and TRPV channel family mRNA in rat spermatogenic cells].
AB  - OBJECTIVE: To investigate the expression of transient receptor potential
      melastatin (TRPM) and transient receptor potential vanilloid (TRPV) channel
      family genes in rat spermatogenic cells. METHODS: Rat spermatogenic cells were
      isolated by a mechanical procedure and the total RNA was extracted using TRIzol
      reagent. TRPM and TRPV channel family genes were amplified by RT-PCR and the
      presence of the target genes was detected by agarose gel electrophoresis. The
      relative gene expression levels were measured by real-time quantitative RT-PCR.
      RESULTS: TRPV5, TRPM3, TRPM4 and TRPM7 mRNAs were expressed in rat spermatogenic
      cells, but TRPV1, TRPV2, TRPV3, TRPV4, TRPV6, TRPM1, TRPM2, TRPM5, TRPM6, TRPM7
      and TRPM8 mRNAs were not detected. The relative expressions of TRPM and TRPV mRNA
      were determined by quantitative real-time RT-PCR. TRPM7 expression was the
      highest among all the TRPM subtypes in rat spermatogenic cells, at a level
      equivalent to (0.0430-/+0.0034)% of beta-actin expression. TRPM3 and TRPM4 were
      also highly expressed, but their expression levels were only approximately 56%
      and 63% of that of TRPM7, respectively. For the TRPV subfamily, only TRPV5 mRNA
      was abundantly expressed at the level of (0.0157-/+0.0029)% relative to that of
      beta-actin. CONCLUSION: TRPV5, TRPM3, TRPM4 and TRPM7 mRNAs were coexpressed in
      spermatogenic cells in rats, among which TRPM4 and TRPM7 mRNA were expressed at
      high levels. TRPM4 and TRPM7 channels may be involved in the regulation of
      growth, differentiation and maturation of rat spermatogenic cells and are
      associated with the generation of the sperms.

PMID- 19114344
TI  - [Prospective study of cystatin C for diagnosis of acute kidney injury after
      cardiac surgery].
AB  - OBJECTIVE: To prospectively study the value of cystatin C in diagnosis of acute
      kidney injury (AKI) in patients after cardiac surgery. METHODS: A total of 132
      patients undergoing cardiopulmonary bypass were enrolled in this prospectively
      study. From each patient, blood samples were collected everyday before and after
      operation to detect the serum creatinine (Scr) and cystatin C levels by enzymatic
      method and particle-enhanced turbidimetric immunoassay (PETIA), respectively, and
      the glomerular filtration rate (eGFR) was estimated using MDRD equation. AKI
      diagnosis was made according to the RIFLE criteria of the Acute Dialysis Quality
      Initiative (ADQI) (R: Scr increased by > or =50%; I: Scr increased by > or =100%;
      F: Scr increased by > or =200%; L: Loss of kidney function; E: End-stage renal
      disease). Another AKI diagnostic criterion was also adopted according to the
      levels of cystatin C increment, namely an increase by > or =50%, > or =100%, and
      > or =200%. RESULTS: Twenty-nine patients (21.9%) developed AKI of varied
      severities, including 10 meeting the R-criteria, 12 the I-criteria, 7 the F
      criteria, with the other 103 patients without AKI serving as the control group.
      Cystatin C of the 29 AKI patients was drastically increased in comparison with
      that of the control group (P<0.001). Significant linear correlation was found
      between cystatin C and Scr (r=0.732, P<0.001) and between [cystatin C]-1 and
      estimated GFR (R=0.803, P<0.001). By the two diagnostic criteria based on
      cystatin C and Scr levels, respectively, the median diagnostic time of AKI was 2
      days (range 1-4 days) and 3 days (range 2-5 days) for R criteria (10 patients,
      P=0.014), 3.5 days (range 1-6 days) and 5 days (range 2-8 days) for I criteria
      (12 patients, P=0.008), and 5 days (range 3-7 days) and 6.5 days (range 4-9 days)
      for F criteria (7 patients, P=0.02), respectively. ROC analysis confirmed
      excellent accuracy of cystatin C in AKI diagnosis (AUC=0.992). With the cut-off
      value of cystatin C increment by > or =50%, the diagnostic sensitivity and
      specificity of AKI was 92% and 95%, respectively. CONCLUSION: Cystatin C can
      serve as a good indicator for AKI diagnosis to allow earlier detection of AKI
      than Scr-based diagnosis in patients after cardiac surgery.

PMID- 19114345
TI  - [Ultrasonic scores combined with blood indexes for screening and predicting
      compensated liver cirrhosis in chronic hepatitis B patients].
AB  - OBJECTIVE: To explore the correlation between ultrasonic scores, routine blood
      tests and stages of hepatic fibrosis in patients with chronic hepatitis B (CHB),
      and identify non-invasive indexes to establish a diagnostic model for liver
      cirrhosis. METHODS: A retrospective analysis of 428 patients with CHB undergoing
      liver biopsies was conducted. The patients' hematology, serum biochemical
      indexes, serum alpha fetal proteins (AFP), serum HBeAg status and ultrasonic
      scores were statistically analyzed. A diagnostic model was established by
      stepwise discriminant analysis, and aspartate aminotransferase (AST) to platelet
      ratio index (APRI) was used to estimate the diagnostic value. RESULTS: Partial
      correlation analysis indicated that platelet, serum albumin, bilirubin, AST,
      ratio of AST to alanine aminotransferase, prothrombin time and ultrasonic scores
      were correlated to the stages of liver fibrosis, and significantly differed
      between patients with and without liver cirrhosis. Logistic regression analysis
      identified ultrasonic scores, platelet, serum bilirubin, albumin and AST as
      indexes affecting the diagnosis of compensated cirrhosis. The area under receiver
      operation curve of model was 0.907. The cirrhosis index (CI) of -0.94 for this
      model was suitable for screening, with specificity of 85.0%, sensitivity of
      81.7%, and accuracy of 84.3%. About 56.2% of the patients' CI was lower than -2.0
      with the negative predictive value of 97.0% and the rate of missed diagnosis of
      3.0%. About 18.2% of the patients' cirrhosis probabilities were above 0.15, with
      positive predictive value of 77.3%, and only 2.7% of the patients had mild
      fibrosis (F2), suggesting that nearly 75% of the patients did not have to receive
      liver biopsies. CONCLUSION: This diagnostic model integrates the ultrasonic
      scores, platelet, serum bilirubin, albumin and AST to enable effective screening
      and prediction of compensated cirrhosis, and can reduce the number of patients
      required to undergo liver biopsy by about 75%.

PMID- 19114346
TI  - [Factors responsible for inter-individual variations in dosage/concentration of
      tacrolimus in renal transplant recipients].
AB  - OBJECTIVE: To identify the factors responsible for the inter-individual
      variations in the dosage/concentration of tacrolimus in renal transplant
      recipients. METHODS: This study involved renal transplant recipients receiving
      immunosuppressive therapy with the tacrolimus, mycophenolate and prednisone
      regimen after the operation. The gender, age, height, body weight, tacrolimus
      dosage, hormone dosage, diarrhea, blood lipids, liver function, renal function,
      albumin, and hematocrit of the patients were recorded at different time points,
      namely in early stage (3, 7, 14, and 30 days postoperatively, 118 cases), at 3
      months (103 cases), 6 months (75 cases) and over one year (119 cases) after the
      operation. The concentrations of tacrolimus and gene polymorphisms at CYP3A5,
      MDR1 3435, MDR1 2677 and MDR1 1236 were also determined in these patients.
      Multiple linear regression was used for analysis of these factors with tacrolimus
      concentration/dosage*body surface area as the independent variable. RESULTS:
      Patients in early stage following renal transplantation showed rather poor
      fitting of the stepwise regression model, which increased obviously 3 months
      after the operation and further increased till reaching a stable level at 6
      months. Multiple factors were found to affect tacrolimus concentration/dosage in
      the early postoperative stage, during which period these factors underwent
      drastic variations and became stable 3 months later. In terms of
      pharmacogenomics, the major factors affecting tacrolimus concentration/dosage
      included MDR1 3435, MDR1 2677 and MDR1 1236 polymorphisms, which vastly varied
      between the patients early after the operation. Of these polymorphic sites,
      CYP3A5 produced only minor effects on tacrolimus concentration/dosage, and was
      not included as an active factor until the stable phase (over 1 year) following
      the transplantation; MDR1 3435 was found to be the predominant factor affecting
      tacrolimus metabolism in the stable phase. Age, liver function, albumin and
      hematocrit were found to be positively correlated to the independent variable
      tacrolimus concentration/dosage*body surface area, and identified as important
      factors responsible for the intra-individual variation of tacrolimus
      dosage/concentration. CONCLUSION: The variations in the factors affecting
      tacrolimus dosage/concentration after renal transplantation are consistent with
      the clinical features of the patients, and these factors vary with the
      postoperative stages. Pharmacogenomic factors produce the most conspicuous effect
      on tacrolimus dosage/concentration, and agents that may interfere with tacrolimus
      metabolism should be avoided after the operation. Age, liver function, albumin
      and hematocrit are also important factors responsible for the variation of
      tacrolimus dosage/concentration.

PMID- 19114347
TI  - [Expressions of HLA class I antigen and CD8 and their clinical significance in
      cervical cancer].
AB  - OBJECTIVE: To examine the expressions of HLA class I antigen and CD8 in various
      cervical diseases and investigate their association with cervical cancer.
      METHODS: The expressions of HLA class I antigen and CD8 in cervical tissues
      sampled from patients with cervical cancer, cervical intraepithelial neoplasia
      (CIN), and chronic cervicitis were detected using SP immunohistochemistry. The
      association of the expressions of HLA class I antigen and CD8 with the
      clinicopathologic indices of the patients was analyzed. RESULTS: The positive
      expression rates of HLA class I antigen in cervical cancer, CIN, and chronic
      cervicitis were 22.6%, 100.0%, and 100.0%, and the positive expression rates of
      CD8 were 22.6%, 95.5%, and 100.0%, respectively. The positive rates of HLA class
      I antigen and CD8 were significantly lower in patients with cervical cancer
      (P<0.01). Patients with stage I cervical cancer had significantly higher positive
      rates of HLA class I antigen and CD8 than those with stage II cervical cancer
      (46.7% vs 0.0%, 46.7% vs 0.0%, both P<0.01). The expressions of HLA class I
      antigen and CD8 decreased with the progression of the clinicopathological stages,
      and may even become undetectable. The expressions of HLA class I antigen and CD8
      were not related to the differentiation degree of the tumor or lymph node
      metastasis (P>0.05). A positive correlation was found between HLA class I antigen
      expression and CD8 expression. CONCLUSION: The expressions of HLA class I antigen
      and CD8 are down-regulated or deleted in CIN and cervical cancer, and they may
      play important roles in the development and progression of CIN and cervical
      cancer.

PMID- 19114348
TI  - [Preparation of nano-nacre artificial bone].
AB  - OBJECTIVE: To assess the improvements in the properties of nano-nacre artificial
      bone prepared on the basis of nacre/polylactide acid composite artificial bone
      and its potential for clinical use. METHODS: The compound of nano-scale nacre
      powder and poly-D, L-lactide acid (PDLLA) was used to prepare the cylindrical
      hollow artificial bone, whose properties including raw material powder scale,
      pore size, porosity and biomechanical characteristics were compared with another
      artificial bone made of micron-scale nacre powder and PDLLA. RESULTS: Scanning
      electron microscope showed that the average particle size of the nano-nacre
      powder was 50.4-/+12.4 nm, and the average pore size of the artificial bone
      prepared using nano-nacre powder was 215.7-/+77.5 microm, as compared with the
      particle size of the micron-scale nacre powder of 5.0-/+3.0 microm and the pore
      size of the resultant artificial bone of 205.1-/+72.0 microm. The porosities of
      nano-nacre artificial bone and the micron-nacre artificial bone were (65.4
      /+2.9)% and (53.4-/+2.2)%, respectively, and the two artificial bones had
      comparable compressive strength and Young's modulus, but the flexural strength of
      the nano-nacre artificial bone was lower than that of the micro-nacre artificial
      bone. CONCLUSIONS: The nano-nacre artificial bone allows better biodegradability
      and possesses appropriate pore size, porosity and biomechanical properties for
      use as a promising material in bone tissue engineering.

PMID- 19114349
TI  - [Hysterectomy after cardiopulmonary resuscitation in patients with obstetric
      hemorrhagic shock].
AB  - OBJECTIVE: To explore the indication of hysterectomy after successful
      resuscitation of cardiac arrest due to obstetric hemorrhagic shock. METHODS: A
      retrospective analysis was conducted in 13 patients with cardiac arrest due to
      obstetric hemorrhagic shock in 7 hospitals of Guangzhou, including 12 patients
      undergoing hysterectomy and 1 undergoing uterine artery embolization. RESULTS: s
      After successful cardiopulmonary resuscitation, only 4 of the 13 patients
      undergoing hysterectomy or uterine artery embolization for continuing uterus
      hemorrhage survived. CONCLUSION: Detailed plans and emergency measures should be
      formulated in the management of high-risk pregnancies. Early diagnosis and active
      treatment of obstetric hemorrhagic shock with hysterectomy or uterine artery
      embolization are critical in preventing cardiac arrest and improving the survival
      of the patients.

PMID- 19114350
TI  - [Effect of vascular endothelial growth factor and tumor necrosis factor receptor
      for treatment of avascular necrosis of the femoral head in rabbits].
AB  - OBJECTIVE: To evaluate the therapeutic effect of vascular endothelial growth
      factor (VEGF) and tumor necrosis factor receptor (TNFR) on avascular necrosis of
      the femoral head in rabbits. METHODS: Avascular necrosis of the femoral head was
      induced in 26 New Zealand white rabbits by injections of horse serum and
      prednisolone. The rabbits were then divided into VEGF/TNFR treatment group, VEGF
      treatment group, and untreated model group, with another 4 normal rabbits as the
      normal control group. In the two treatment groups, the therapeutic agents were
      injected percutaneously into the femoral head. Enzyme-linked immunosorbent assay
      was performed to determine the concentration of TNF-alpha in rabbit serum
      followed by pathological examination of the changes in the bone tissues, bone
      marrow hematopoietic tissue and the blood vessels in the femoral head. RESULTS:
      Compared with the model group, the rabbits with both VEGF and TNFR treatment
      showed decreased serum concentration of TNF-alpha with obvious new vessel
      formation, decreased empty bone lacunae in the femoral head and hematopoietic
      tissue proliferation in the bone marrow cavity. CONCLUSION: Percutaneous
      injection of VEGF and TNFR into the femoral head can significantly enhance bone
      tissue angiogenesis and ameliorate osteonecrosis in rabbits with experimental
      femoral head necrosis.

PMID- 19114351
TI  - [Association of glycosylated hemoglobin A1c control with the complications in
      type 2 diabetic patients].
AB  - OBJECTIVE: To investigate the status of glycosylated hemoglobin A1c (GHbA(1c))
      control in type 2 diabetic patients and its relation to diabetic complications.
      METHODS: A total of 676 patients with type 2 diabetes were investigated for
      GHbA(1c) level and the diabetic complications. The patients were divided into two
      groups with GHbA(1c) >7% and GHbA(1c)< or =7%, and the relation of GHbA(1c) with
      the complications was analyzed. RESULTS: The rate of good GHbA(1c) control
      (GHbA(1c)< or =7%) was 35.1% (237/676) in these patients, and 64.9% (439/676) of
      the patients showed poor GHbA(1c) control (GHbA(1c)>7%). The rates of
      hypertension and cerebralovascular complications were significantly higher in
      patients with GHbA(1c)>7% than in those with GHbA(1c)< or =7% (69.9% vs 55.7%,
      and 21.8% vs 8.9%, respectively, P<0.001), but the rate of coronary heart disease
      was comparable between the two groups (18.7% vs 17.3%, P>0.05). The patients with
      poor GHbA(1c) control had significantly higher incidences of diabetic peripheral
      neuropathy and fatty liver than those with good GHbA(1c) control (46.0% vs 35.0%,
      and 36.9% vs 25.3%, respectively, P<0.01), but no significant differences were
      found in the incidences of diabetic nephropathy (18.7% vs 16.5%), diabetic
      retinopathy (30.8% vs 27.4%) or diabetic feet (5.0% vs 3.8%) between the two
      groups (P>0.05). CONCLUSION: Type 2 diabetic patients have generally low rate of
      successful GHbA(1c) control, which can be associated with the occurrence of
      diabetic complications, suggesting the necessity of more rigorous diabetic health
      education and GHbA(1c) monitoring in these patients.

PMID- 19114352
TI  - [Synthesis and characterization of folic acid-conjugated chitosan nanoparticles
      as a tumor-targeted drug carrier].
AB  - OBJECTIVE: To synthesize and characterize paclitaxel (PTX)-loaded folate
      conjugated chitosan (FA-CTS/PTX) nanoparticles and evaluate its cytotoxicity in
      vitro. METHODS: CTS/PTX and FA-CTS/PTX nanoparticles were prepared using
      reductive amidation and ionic gelation of chitosan with tripolyphosphate anions
      (TPP). The particle size was determined by laser scattering and the morphology
      observed using transmission electron microscopy, and the PTX content in the
      nanoparticles was determined using ultraviolet spectrophotometer at 227 nm. The
      in vitro cytotoxicity of the nanoparticles against HeLa cells was evaluated by
      MTT assay. Fluorescence microscopy was used to observe the HeLa cells incubated
      with FA-chitosan nanoparticles in the presence or absence of folic acid in the
      culture medium. RESULTS: PTX loading did not cause adhesion of the FA-CTS
      nanoparticles, which presented with uniform spherical morphology with an average
      diameter of 282.8 nm. The loading and encapsulation efficiencies of FA-CTS/PTX
      were 9.0% and 75.4%, respectively. The FA-CTS nanoparticles showed a greater
      extent of intracellular uptake in the absence of folic acid, indicating that the
      cellular uptake of the nanoparticles occurred through endocytosis mediated by the
      folate receptors. The PTX-loaded FA-CTS nanoparticles exhibited potent
      cytotoxicity against HeLa cells, an effect 2- to 3-fold stronger than that of PTX
      loaded CTS nanoparticles. CONCLUSION: FA-CTS can be a promising drug carrier with
      high efficiency in condensing drug, good tumor-targeting ability and low
      cytotoxicity.

PMID- 19114353
TI  - [Mechanisms of G2/M cycle arrest induced by topo IIalpha and II beta inhibitors
      in H460 cells].
AB  - OBJECTIVE: To compare the mechanisms of G(2)/M cycle arrest induced by topo
      IIalpha and IIbeta inhibitors in H460 cells. METHODS: The inhibitory effects of
      XK469, adriamycin and etoposide on H460 cell growth were analyzed by MTT assay.
      The changes in cell cycle and expressions of cdc2, phos-cdc2 and 14-3-3sigma
      proteins induced by these 3 topo II inhibitors were detected by flow cytometry
      and Western blotting, respectively. RESULTS: Both of the two types of topo II
      inhibitor resulted in dose-dependent G(2)/M phase arrest and growth inhibition of
      H460 cells, but XK469 failed to induce 14-3-3sigma protein expression as
      adriamycin and etoposide did. CONCLUSION: Topo IIalpha and topo IIbeta inhibitors
      induce growth inhibition of H460 cells possibly through two different mechanisms,
      namely the 14-3-3sigma-dependent pathway and the 14-3-3sigma-independent pathway,
      but further functional inhibition test of 14-3-3sigma is needed to confirm this
      hypothesis.

PMID- 19114354
TI  - [Therapeutic effect of embolization of brain arteriovenous malformation with non
      adhesive liquid embolic agent].
AB  - OBJECTIVE: To observe the clinical and pathological characteristics of brain
      arteriovenous malformations (BAVM) embolized with the non-adhesive aqueous
      embolic agent Onyx and evaluate its application in comprehensive treatment of
      BAVM. METHODS: Thirty-four patients underwent BAVM embolization using Onyx, and
      their clinical manifestations, architecture of the malformed vessels, emblization
      procedure, and complications associated with the procedures were recorded. The
      resected tissues after embolization with Onyx were observed with electron
      microscope, and the prognosis of the patients was estimated with modified Rankin
      Score (mRS). RESULTS: These patients included 21 male and 13 female patients with
      a mean age of 30.45-/+11.81 years and an estimated mean size of the nidus of 3.98
      /+1.43 cm. The patients received a total of 52 endovascular treatment procedures
      with Onyx to embolize 86 feeding pedicals, which resulted in an average estimated
      size reduction of the nidus of (72.35-/+21.26)%. Complications associated with
      the procedure occurred in 7 patients, and 23 patients received surgical resection
      or radiosurgery after embolization. Follow-up of the patients for 6 months to 4
      years showed that the mRS was below 3 in 32 cases and > or =3 in 2 cases.
      Vasodilatation, brain tissue edema surrounding the nidus, and inflammatory cell
      infiltration were observed in the resected tissues after embolization. In some
      major feeding pedicals, thrombus recanalization was observed after embolization
      with Onyx (diameter> or =3 mm). CONCLUSION: Endovascular treatment of BAVM with
      Onyx can achieve high occlusion rate, enhance the safety of operation and
      radiosurgery, and improve the clinical prognosis of the patients.

PMID- 19114355
TI  - [Comparison between Coulter LH-750 and URIT-12 for measuring hemoglobin
      concentration].
AB  - OBJECTIVE: To evaluate the feasibility of URIT-12 hemoglobin analyzer for fast
      measurement of hemoglobin concentration. METHODS: Hemoglobin concentration was
      detected in 100 random blood samples using URIT-12 hemoglobin analyzer and
      Coulter LH-750 hematology analyzer. RESULTS: The two analyzers showed good
      correlation of the results (r=0.994) without significant difference between them
      (P>0.05). The linear range of URIT-12 hemoglobin analyzer was 46-240 g/L, and in
      the repeated measurements (20 times) of 3 batches of blood samples with low,
      moderate and high hemoglobin concentrations, the within-batch coefficient of
      variation of URIT-12 hemoglobin analyzer, from low to high concentrations, were
      2.13%, 2.17%, and 2.33%, respectively. In the measurement of 4 batches of high
      fat, high-bilirubin, high-globin and high-white-blood-cell blood samples, the
      interference rate of the former 3 samples were all less than 4% by the two
      devices, but that of the fourth sample was 10% by URIT-12 hemoglobin analyzer and
      7% by Coulter LH-750 analyzer. CONCLUSION: The results detected by URIT-12
      hemoglobin analyzer have high accuracy and precision and is easy to operate, fast
      testing and portable.

PMID- 19114356
TI  - [Study on the roles of voltaged potassium channels in acute hypoxic pulmonary
      vasoconstriction].
AB  - OBJECTIVE: To investigate the role of voltage-gated potassium channels in the
      acute hypoxic pulmonary vasoconstriction. METHODS: Thirty Wistar rats were
      divided into two groups, namely the normoxic group and hypoxic group. The single
      smooth muscle cell was obtained from the pulmonary artery of Wistar rats with
      acute enzymatic digestion method. The conventional whole-cell patch clamp
      technique was used to record the resting membrane potential(Em) and the potassium
      currents of voltage-gated potassium channel (IKv) in rat pulmonary arterial
      smooth muscle cells(PASMC). Intracellular application of Kv1.2, Kv1.3, Kv1.5, and
      Kv2.1 antibodiese1:125ewas conducted through the whole-cell patch clamp system.
      RESULTS: Em of PASMC was depolarized in hypoxia compared with that of control
      cells. The mixture of Kv1.2, Kv1.3, Kv1.5, and Kv2.1 antibodiese1:125e
      depolarized Em and inhibited Ikv in PASMC from normoxic rat,whereas the mixture
      of Kv1.2, Kv1.3, Kv1.5, Kv2.1 antibodiese1:125ehad no effects on Ikv and Em in
      hypoxic rats. CONCLUSION: Kv1.2, Kv1.3, Kv1.5, Kv2.1 might be oxygen sensitive
      potassium channels which mediated acute hypoxic pulmonary vasoconstriction.

PMID- 19114357
TI  - [Role of membrane-bound human leukocyte antigen G in inducing immune tolerance
      after allogeneic hematopoietic stem cell transplantation].
AB  - OBJECTIVE: To evaluate the role of human leukocyte antigen G (HLA-G) in the
      better effect of allogenetic bone marrow transplantation than that of peripheral
      blood stem cell transplantation. METHODS: Flow cytometry was used to detect the
      expression of membrane-bound HLA-G (mHLA-G) on donor peripheral blood (PBC) or
      bone marrow (BM) mononuclear cells. The levels of soluble HLA-G (sHLA-G) in the
      plasma and bone marrow fluid were determined using enzyme-linked immunosorbent
      assay (ELISA) before and after granulocyte colony-stimulating factor (G-CSF)
      mobilization. RESULTS: The mean levels of mHLA-G after G-CSF mobilization in the
      PBC and BM were significantly higher than that before G-CSF mobilization (P=0.001
      and 0.000), but the plasma levels of sHLA-G showed no significant changes after
      the mobilization (P=0.279). The mean levels of sHLA-G in the BM fluid
      significantly increased (P=0.002) to a level higher than that in the PBC after G
      CSF mobilization (P=0.004). CONCLUSION: HLA-G plays an important role in immune
      tolerance after hematopoietic stem cell transplantation with G-CSF mobilization.

PMID- 19114358
TI  - [Comparison of the short-term outcomes of liver transplant recipients receiving
      liver grafts from brain-death and non-heart-beating donors].
AB  - OBJECTIVE: To compare the short-term outcomes of liver transplantation recipients
      receiving liver grafts from brain-death and non-heart-beating donors and evaluate
      the safety of liver grafts from brain-death donors. METHODS: A total of 130
      patients receiving liver transplantation between January, 2006 and December, 2007
      were retrospectively analyzed, including 9 patients receiving liver graft from
      brain-death donors and 121 with grafts from non-heart-beating donors. The
      operative time, anhepatic time, bleeding volume, postoperative complications and
      short-term survival were compared between the two groups. RESULTS: The operative
      time, anhepatic time, bleeding volume, postoperative complications and short-term
      survival showed no significant differences between the two groups. CONCLUSION:
      The short-term outcome of recipients receiving liver grafts from brain-death
      donors is similar to that of recipients receiving grafts from non-heart-beating
      donors, indicating the safety of clinical use of the liver grafts from brain
      death donors.

PMID- 19114359
TI  - [Prediction of fetal hypoxia by measuring middle cerebral and umbilical artery
      resistance index in fetuses with umbilical cord around the neck in late
      pregnancy].
AB  - OBJECTIVE: To investigate the value of middle cerebral artery (MCA) and umbilical
      artery (UA) resistance index in predicting fetal hypoxia in fetuses with
      umbilical cord around the neck in late pregnancy. METHODS: Eighty normal fetuses
      between 38 and 40 weeks of gestation and 88 fetuses with umbilical cord around
      neck were measured for MCA and UA pulsatility index (PI), resistance index (RI)
      and the peak-systolic/diastolic ratio (S/D) by means of color Doppler
      ultrasonography, and the resistance index ratio was calculated. Fetuses with
      umbilical cord around neck were estimated according to the measured normograms
      for the presence of fetal hypoxia, and the results were evaluated by diagnostic
      test. RESULTS: Significant differences were found in MCA and UA resistance index
      ratio between the groups (P<0.01). There was no significant difference in the
      resistance index ratio between the normal group and around the neck (one round)
      group (P>0.05), but significant difference was found between normal group and
      around the neck (two rounds and more) group (P<0.01), and between the two arounds
      and one round groups (P<0.05). The sensitivity and specificity of MCA and UA
      resistance index and resistance index ratio in predicting fetal hypoxia of
      fetuses with umbilical cord around neck was 43%, 85%, 92%, 83%, 89%, and 100%,
      respectively. CONCLUSION: MCA and UA resistance index ratio is a better indicator
      than its resistance index in predicting fetal hypoxia of fetuses with umbilical
      cord around neck, and may help in early detection of fetal hypoxia for a
      diagnosis before fetal distress.

PMID- 19114360
TI  - [Polymorphisms of human papillomavirus type 81 L1 gene in patients with cervical
      lesions in Guangdong].
AB  - OBJECTIVE: To investigate the positivity rates and genetic polymorphism of human
      papillomavirus (HPV) type 81 (HPV81) L1 gene in patients with cervical cancer in
      Guangdong. METHODS: HPV L1 genes fragment in 1200 positive cervical samples
      detected with HC-II for high-risk HPV DNA were amplified by HPV-specific PCR with
      consensus primers, and the L1 genes of HPV81 were sequenced for mutation
      analysis. RESULTS: Four HPV81-positive cases were found in the total of 1200
      cases for the positivity rate of 0.33%. Point mutations of HPV81 L1 gene were
      found in all of the samples. CONCLUSION: Compared with the HPV81 prototypes
      published in GenBank, several new point mutations are found in the L1 genes of
      the HPV81 in Guangdong, and these mutations are close to those found in Japan.

PMID- 19114361
TI  - [Effects of resveratrol on the release of Glu and Gln in cultured rat astrocytes
      with stretch injury].
AB  - OBJECTIVE: To study the effects of resveratrol on amino acid release in cultured
      astrocytes with stretch injury and explore its possible mechanism for central
      nervous system protection. METHODS: Cultured rat astrocytes were treated with
      different concentrations of resveratrol for 12 h and the subsequent changes in
      Glu and Gln release and lactate dehydrogenase(LDH) leakage were examined after
      stretch injury. RESULTS: High-performance liquid chromatography showed that
      stretch injury increased Glu release from the astrocytes (P<0.05), and at the
      concentration of 1 micromol/L, resveratrol further increased Glu release
      (P<0.05), whereas at 100 micromol/L, resveratrol obviously inhibit Glu release
      (P<0.05). LDH leakage increased significantly after stretch injury of the
      astrocytes (P<0.05), and resveratrol acted to further increase LDH leakage at 1
      micromol/L but inhibited LDH leakage at 100 micromol/L (P<0.05). CONCLUSION:
      Resveratrol can inhibit the release of Glu and LDH leakage from rat astrocytes to
      protect the cells from stretch injury.

PMID- 19114362
TI  - [Effects of neuraxial block and general anesthesia on tumor metastasis in rats].
AB  - OBJECTIVE: To investigate the effects of different anesthesia methods on immune
      surveillance and tumor metastasis in tumor-bearing rats. METHODS: Seventy-two
      Fischer 344 rats were randomly assigned into 3 equal groups and anesthetized for
      1 h with ketamine (group K), propofol (group P), or neuraxial block (group B).
      All the rats were subjected to laparotomy followed by intravenous injection of
      MADB106 tumor cells, and 24 h after the injection, the number and activity of
      circulating CD3(+), CD4(+), CD8(+), and D4(+)/CD8(+) lymphocyte subsets and NK
      celleCD161a(+)ewere assessed. Three weeks later, the lung metastases were
      counted. RESULTS: Compared with those in group B, the numbers of CD3(+), CD4(+),
      CD8(+), and CD161a(+) lymphocytes and the activity of circulating NK cells were
      significantly reduced, and the lung metastases of MADB106 increased significantly
      in groups K and P (P<0.05 or 0.01 ). The activity of immune surveillance in group
      K was significantly lower than that in group P except for CD8(+) cells, and the
      tumor metastases in group K increased significantly in comparison with those in
      group P (P<0.05 or 0.01). CONCLUSION: Neuraxial block provides protection of the
      activity of immune surveillance and reduces tumor metastases in tumor-bearing
      rats compared with general anesthesia.

PMID- 19114363
TI  - [Artesunate suppresses human endometrial carcinoma RL95-2 cell proliferation by
      inducing cell apoptosis].
AB  - OBJECTIVE: To investigate the inhibitory effect of artesunate on human
      endometrial carcinoma RL95-2 cell line proliferation in vitro and the possible
      mechanisms. METHODS: The inhibitory effect of artesunate on the cell
      proliferation was assessed with MTT assay. Transmission electron miscrosopy was
      used to observe the morphological change of the cells after the treatment. Flow
      cytometry was performed to examine the changes in the cell cycle, reactive oxygen
      species (ROS) levels (with DCFH-DA labeling) and mitochondrial membrane potential
      (rhodamine123 staining), and caspase-3 activity was detected by
      immunohistochemistry. RESULTS: Artesunate inhibited the proliferation of RL95-2
      cells with an IC(50) of 26.29 microg/ml. Transmission electron microscopy
      revealed early apoptotic changes of the cells with obvious chromatin
      fragmentation. The cell cycle arrest at G(0)/G(1) phase was observed by flow
      cytometry, and immunohistochemistry demonstrated caspase-3 positivity in
      cytoplasm. ROS generation in the cells increased obviously after treatment with
      artesunate for 72 h, which also resulted in lowered mitochondrial membrane
      potential. CONCLUSION: Artesunate suppressed the proliferation of RL95-2 cells in
      vitro possibly by inducing cell apoptosis.

PMID- 19114364
TI  - [Anti-CD25 monoclonal antibody with antithymocytic globulin for steroid-resistant
      severe acute graft-versus-host disease after unrelated donor hematopoietic stem
      cell transplantation].
AB  - OBJECTIVE: To study the effect of anti-CD25 monoclonal antibody (mAb) combined
      with antithymocytic globulin (ATG) in the treatment of severe steroid-resistant
      acute graft-versus-host disease (aGVHD) after unrelated donor hematopoietic stem
      cell transplantation (UD-HSCT). METHODS: Ten leukemic patients who developed
      severe steroid-resistant aGVHD during UD-HSCT received a standard dose of anti
      CD25 mAb and a medium or low dose of ATG. The effect on aGVHD control, patients'
      survival, infection and relapse after the therapy were analyzed. RESULTS: Eight
      of the 10 patients had complete remission and 2 had partial remission after the
      combined therapy. In the 8 patients with complete remission, 2 developed third
      degree aGVHD 3-3.5 months after the transplantation, and were managed with a
      second combined therapy to successfully achieve complete remission. In the total
      of 12 combined treatments, the median time of therapeutic effect was 5 days (3-10
      days); the median complete relief time was 12 days (8-30 days) in the 10 cases.
      Among the 8 patients who survived for more than 3 months, 7 were diagnosed to
      have chronic GVHD including 4 with extensive chronic GVHD. No relapse of leukemia
      was found in these patients. Five patients survived the 2-year-long follow-up
      after the transplantation with survival time over 2 years; of the 5 patients who
      died within 2 years after the transplantation, 1 survived for more than one year,
      and 4 for less than 6 months. Two patients died from invasive fungal infection,
      two from aGVHD and one from cGVHD-induced multiple organ failure. CONCLUSION:
      Anti-CD25 mAb combined with ATG has good therapeutic effect on steroid-resistant
      sever aGVHD and may help achieve high complete remission rate and long-term
      survival in leukemic patients after UD-HSCT.

PMID- 19114365
TI  - [RNA interference-mediated silencing of cytochrome P450 3A4 gene in CHL-3A4
      cells].
AB  - OBJECTIVE: To investigate the effect of small hairpin interfering RNA (shRNA) in
      suppressing cytochrome P450 3A4 (CYP3A4) gene expression in CHL-3A4 cells.
      METHODS: Three shRNA expression vectors targeting CYP3A4 gene (CYP3A4 I, C YP3A4
      II, and CYP3A4 III, respectively) were designed, synthesized and transfected into
      CHL-3A4 cells via liposomes. The inhibitory effect of shRNA on CYP 3A4 gene
      expression was detected by Western blotting and RT-PCR, and the effect of shRNA
      transfection in suppressing cyclophosphamide-induced cytotoxicity was measured
      using MTT assay. RESULTS: The vector carrying CYP3A4 III shRNA significantly
      reduced the expression of CYP3A4 gene at both the mRNA (75%) and protein levels
      (80%) in CHL3A4 cells. The cytotoxicity of cyclophosphamide was markedly
      inhibited by CYP3A4 III-mediated suppression of CYP3A4 gene expression by 75% in
      CHL-3A4 cells. CONCLUSION: The vector-mediated RNA interference can suppress
      CYP3A4 gene expression in CHL-3A4 cells, and RNA interference technique provides
      a new means for studying cytochrome P450 gene function in mammalian cells.

PMID- 19114366
TI  - [Correlation between magnetic resonance imaging findings and proliferating cell
      nuclear antigen expression in peripheral lung cancer].
AB  - OBJECTIVE: To study the correlation between magnetic resonance imaging (MRI)
      findings and proliferating cell nuclear antigen (PCNA) expression in peripheral
      lung cancer. METHODS: The expression of PCNA was detected by means of SABC
      immunohistochemistry in 45 cases of surgically and pathologically confirmed
      peripheral lung cancer. The correlation between PCNA expression in the tumors and
      the MRI findings was analyzed. RESULTS: PCNA expression was correlated to the
      differentiation, tumor size, lobulation, and mediastinal lymph node metastasis of
      the tumors (P<0.05), but not to the histological type, clinical stage, pleural
      retraction, spiculation, or signal feature. CONCLUSION: Correlations are found
      between MRI findings of lung cancer and abnormal expression of PCNA.

PMID- 19114367
TI  - [Predisposing factors for postoperative epilepsy in patients with gliomas].
AB  - OBJECTIVE: To explore the predisposing factors for postoperative epilepsy in
      patients with gliomas. METHODS: A total of 258 glioma patients with complete
      clinical data receiving cranial surgeries were analyzed retrospectively. With
      gender, age, predominant symptoms, positive signs, history of preoperative
      epilepsy, time of epilepsy onset, tumor location, surgical approaches, cortical
      injury, arterial and venous injury, scope of tumor resection, postoperative
      edema, tumor pathology, tumor recurrence, number of operation, radiation therapy
      as the independent variables, the occurrence of postoperative epilepsy was
      analyzed as the dependent variable using logistic regression to identify the risk
      factors for postoperative epilepsy. RESULTS: History of preoperative epilepsy,
      surgical approaches, postoperative edema, tumor pathology and tumor recurrence
      were identified as the risk factors for postoperative epilepsy in glioma
      patients. CONCLUSIONS: Postoperative epilepsy severely affected the quality of
      life of glioma patients, and rigorous treatment targeting the risk factors may
      decrease the occurrence of postoperative epilepsy.

PMID- 19114368
TI  - [Value of computed tomography and magnetic resonance imaging in diagnosis and
      differential diagnosis of small hepatocellular carcinoma].
AB  - OBJECTIVE: To analyze the computed tomography (CT) and magnetic resonance imaging
      (MRI) findings of small hepatocellular carcinoma to improve the accuracy in the
      diagnosis. METHODS: This retrospective analysis involved 41 patients with small
      hepatocellular carcinoma cases confirmed by pathological examination of the
      biopsy samples or follow-up. These patients were assessed for CT and MRI findings
      including lesion size, density or signal intensity, enhancement patterns, and
      presence of tumor capsules. RESULTS: On unenhanced CT images, small
      hepatocellular carcinomas were displayed mainly as low-density masses, and the
      majority of tumors presented with low signal intensity on T1-weighted unenhanced
      MR images with increased signal intensity on T2-weighted images in comparison
      with the surrounding liver parenchyma. Most of tumors showed intense enhancement
      during the arterial phase (CT in 15 cases and MRI in 13 cases), but some appeared
      isointense to the liver parenchyma (CT in 4 cases and MRI in 4 cases). In portal
      and delayed phases, the tumors typically had lower signal intensity than that of
      the surrounding liver tissues (CT in 25 cases and MRI in 12 cases) with
      enhancement of the tumor capsules (13 cases). CONCLUSION: Dynamic enhanced
      scanning can be more informative of the pathology and blood supply of small
      hepatocellular carcinoma. Early and late arterial phase imaging may help in
      detecting the small lesions and in making differential diagnosis.

PMID- 19114369
TI  - [Analysis of the outcome of extracorporeal shock wave lithotripsy for renal
      calculia].
AB  - OBJECTIVE: To evaluate the factors affecting the efficacy of extracorporeal shock
      wave lithotripsy (ESWL) for renal calculi. METHODS: Between January, 2004 and
      January, 2007, 316 patients (212 men and 104 women) with renal stone underwent
      ESWL. The correlations of the patients' age, gender, body mass index (BMI),
      disease course, pain, hematuria, stone size, location, side, number and
      hydronephrosis to the outcome of the treatment was analyzed. The treatment
      success was defined as complete clearance of the stones or residual stone
      fragments <0.4 cm, and ESWL was considered unsuccessful with residual stones>0.4
      cm. RESULTS: The overall success rate was 75.3% (238/316) in these patients.
      Significant difference in stone clearance rates was observed in patients with
      stone size of 0.5-1.0 cm (90.3%, 167/185), 1.0-2.0 cma(69.6%, 55/79), and >2.0 cm
      (30.8%, 16/52) (P<0.05). The success rates differed significantly between cases
      of pelvic stones (83.1%, 118/142) and those of caliceal stones (69.0%, 120/174)
      (P<0.05). But in cases of caliceal stones, the success rates were comparable
      between cases with stones at the upper calyx (71.7%, 43/60), middle calyx (68.9%,
      31/45), and lower calix (66.7%, 46/69) (P>0.05). Patients with single stones had
      significantly higher success rate (82.9%,170/205) than those with multiple stones
      (61.3%, 68/111) (P<0.05). The patients' gender, age, disease course, pain,
      hematuria, stone side and hydronephrosis did not produce significant impact on
      the outcome of the treatment (P>0.05). CONCLUSION: Stone size, location and
      quantity are significant independent factors affecting the outcome of ESWL for
      renal stones.

PMID- 19114370
TI  - [Pleuropulmonary blastoma in an adult women with pleurorrhea as the major
      clinical manifestation: report of a case].
AB  - OBJECTIVE: Pleuropulmonary blastoma (PPB) is a rare dysontogenetic neoplasm in
      children and has been recognized as a distinct clinicopathological entity
      different from the ordinary pulmonary blastoma of adulthood. We report a very
      rare adult case of PPB. A 43-year-old female patient presented with massive
      pleural infusion, and a misdiagnosis of pleural tuberculosis (TB) was made on the
      basis of ultrasound scan and CT images, for which therapy with TB drugs was
      administered for 3 weeks. Subsequent operation and pathologic examination of the
      mass revealed a multicystic neoplasm consisting of malignant mesenchymal cells
      immunohistochemically positive for vimentin and actin. Local recurrence occurred
      in the left pleural 20 months after the surgical tumor resection and 4 cycles of
      adjuvant chemotherapy.

PMID- 19114371
TI  - [Assessment of nutritional metabolism in severe burned patients by bioelectrical
      impedance analysis].
AB  - OBJECTIVE: To detect body composition and evaluate the influence of body
      composition on nutritional assessment of burned patients by BIA(bioelectrical
      impedance analysis). METHODS: Body composition was determined in 38 burned
      patients (32male, 6female) with total burn area 10% approximately 80%(mean
      33.1%+17.61%) by BIA during day 1 to day 70 after burns. All patients were
      divided into two groups: 20 cases in group A (total burn areas >30%), 18 cases in
      group B (TBSA <30%). Adequate number calories provided by indirect calorimetry.a
      RESULTS: two patients died of MODS in the two groups, 36 patients were survived,
      mean days of stay hospital 33.1+17.6, the value of lean body mass and body fat
      mass are gradually decreased, lean body mass is especially lower in the two
      groups despite provided adequate number calories, there is a significant
      difference in static analysis in the two groups(P<0.05).a CONCLUSION: The serve
      catabolism is prevalent in treatment procedure of the burned patients with major
      burn, the lower of lean body mass is not changing despite provide adequate
      caloris in the two groups. It is a simple and precisely method that bioelectrical
      impedance analysis could measure body composition; it may help objectively assess
      nutritional status of severe burned patients.

PMID- 19114372
TI  - [Color Doppler and contrast-enhanced ultrasonography for assessment of vascular
      perfusion in porcine liver allografts with acute graft rejection].
AB  - OBJECTIVE: To investigate the feasibility of evaluating hepatic blood perfusion
      after liver transplantation using color Doppler and contrast-enhanced
      ultrasonography and the diagnostic value of hepatic blood perfusion for acute
      graft rejection. METHOD: In this before-after study with quantitative analysis,
      contrast-enhanced sonography was performed with simultaneous liver function
      monitoring in porcine models of allograft liver transplantation before and after
      the operation. RESULTS: In pigs with acute graft rejection, the AUC decreased
      significantly after transplantation as compared with that of non-rejection
      transplant group (F=11.069, P=0.011), but the parameters including A, Alpha, C,
      t(0), DPI, or TTP showed no significant differences between the two groups.
      CONCLUSIONS: Pulse-inversion contrast harmonic imaging combined with acoustic
      quantitative technology can be an efficient means for evaluating blood perfusion
      in the liver allograft, and the TIC obtained using this method possesses high
      values for quantitative evaluation of liver allograft rejection.

PMID- 19114373
TI  - [Effect of progesterone on high mobility group Box-1 protein-induced interleukin
      6 release by human umbilic vein endothelial cells].
AB  - OBJECTIVE: To study the effect of progesterone on interleukin-6 (IL-6) release
      from human umbilic vein endothelial cells (HUVECs) induced by high mobility group
      box-1 protein (HMGB1). METHOD: The recombinant expression plasmid pET14b-HMGB1
      was constructed and transformed into competent E.coli BL21 cells to obtain HMGB1
      protein, which was purified with chromatography on Ni-NTA Sepharose column.
      Cultured HUVECs were treated with purified HMGB1 protein alone at the
      concentrations 0, 10, 100, 500, and 1000 ng/ml, progesterone alone at the
      concentrations of 0, 0.1, 1, 10, 100 mmol/L, or with both HMGB1 protein (500
      ng/ml) and progesterone at the terminal concentrations of 0, 0.1, 1, 10, and 100
      mmol/L. Twenty-four hours later, the supernatant of the cell culture medium was
      collected to detect the levels of IL-6 using enzyme-linked immunosorbent assay
      (ELISA). RESULTS: The IL-6 levels in HUVEC culture medium was slightly decreased
      after treatment with low-concentration HMGB1 but increased obviously following
      treatment with high-concentration HMGB1, and these effects could be dose
      dependently inhibited by progesterone. Progesterone alone did not result in any
      noticeable changes of IL-6 levels in the cell culture medium. CONCLUSIONS:
      Progesterone can dose-dependently inhibit HMGB1-induced IL-6 release from HUVECs,
      suggesting the protective role of progesterone in endotoxemia.

PMID- 19114374
TI  - [Drug-eluting stent implantation for unprotected left main coronary artery
      disease: immediate and long-term outcomes].
AB  - OBJECTIVE: To evaluate the safety and efficacy of drug-eluting stent (DES)
      implantation in selective patients with left main coronary artery disease.
      METHOD: From October 2002 to November 2007, 44 consecutive patients underwent
      percutaneous coronary interventions (PCI) on left main coronary artery lesions,
      including 5 patients with concurrent left ventricular dysfunction (ejection
      fraction<40%), 2 with chronic respiratory dysfunction and 5 with chronic renal
      failure. The findings in coronary angiography, procedural success rate, severe
      complications and the follow-up results of the patients were analyzed. RESULTS:
      The immediate procedural success rate was 100% in these patients without any
      severe complications. No non-fatal acute myocardial infarction or emergency
      coronary artery bypass grafting (CABG) was performed and death occurred in none
      of the cases during hospitalization. In the follow-up period for 14.2-/+9.3 (6
      65) months after PCI, no subacute or late thromboses were found. One patient died
      from heart failure 4 months after PCI, and 6 patients (13.6%) experienced
      recurrent angina. Thirty-seven patients (84.1%) were free of any major
      cardiovascular events (MACE) after the procedure. A repeat coronary angiography
      was performed in 35 patients (79.5%) within 6 months after PCI, and 3 (8.6%) of
      them were confirmed to have restenosis, including 1 patient with distal
      bifurcation restenosis who were subsequently treated with CABG and two patients
      with side-branch ostium restenosis managed with cutting balloon dilation.
      CONCLUSIONS: Implantation of drug-eluting stents is safe and effective for
      management of left main coronary artery disease with good immediate and long-term
      outcomes.

PMID- 19114375
TI  - [Mechanisms of losartan for inhibition of myocardial fibrosis following
      myocardial infarction in rats].
AB  - OBJECTIVE: To investigate the effect of losartan on cardiac mineralocorticoid
      receptor (MR) mRNA in rats after acute myocardial infarction (AMI). METHOD: AMI
      was induced in male SD rats by ligation of the left coronary artery. The survived
      rats were randomly divided into AMI group, losartan group, and sham-operated
      group. The cardiac functions of the rats were assessed by echocardiogram and
      hemodynamics, and the contents of angiotensin II (Ang II) and aldosterone (Ald)
      in the myocardial tissues were determined by radioimmunoassay. The collagen
      density in the myocardial tissues were calculated by Masson's trichrome staining
      and the expression of MR mRNA were determined by real-time quantitative
      fluorescent PCR. RESULTS: Both the contents of AngII and Ald in the myocardial
      tissues increased significantly in AMI group compared with those in the sham
      operated group (P<0.01). The expression of MR mRNA and collagen density in the
      myocardial tissues also increased significantly than that in sham-operated group
      (P<0.01). After four weeks of losartan treatment, the contents of AngII and Ald
      in the myocardial tissues decreased significantly (P<0.05) and the expression of
      MR mRNA was also considerably lowered (P<0.01) in comparison with those in the
      AMI group. Treatment with losartan also resulted in significant decrease of the
      collagen density in the myocardial tissues. CONCLUSIONS: Losartan may reduce
      reactive fibrosis not only by attenuating the Ald signaling pathway but also by
      decreasing the expression of MR.

PMID- 19114376
TI  - [Therapeutic effect of Tripterygium wilfordii multiglycosides on proteinuria in
      kidney transplant recipients].
AB  - OBJECTIVE: To study the effect of multiglycosides of Tripterygium wilfordii (MTW)
      for treatment of proteinuria in kidney transplant recipients. METHOD: Forty-five
      kidney transplant recipients with proternuria were randomized into 3 groups
      (n=15) and received full daily dose (1 mg/kg) MTW, half dose (0.5 mg/kg) MTW or
      no MTW (control) in addition to immunosuppressant therapy. The 24-hour urinary
      protein (24 h Upro), blood urea nitrogen (BUN), serum creatinine (Scr), dose of
      ciclosporin and the adverse effects of MTW were recorded. RESULTS: MTW at both
      the full dose and half dose significantly reduced the 24 h Upro as compared to
      exclusive immunosuppressant therapy (P<0.05). The therapeutic dose of ciclosporin
      in patients with full and half dose of MTW was significantly lower than that in
      the control group (P<0.05), and the patients receiving full dose MTW showed
      greater adverse effects than those having half dose MTW (P<0.05). CONCLUSIONS:
      MTW can significantly ameliorate proteinuria, reduce the therapeutic dose of
      ciclosporin and protect the renal function in kidney transplant recipients. While
      producing similar therapeutic effect to routine full dose, long-term use of half
      dose MTW may reduce the adverse effect associated with MTW.

PMID- 19114377
TI  - [Modified laparoscopic transabdominal preperitoneal repair of groin hernias].
AB  - OBJECTIVE: To assess the clinical value of modified transabdominal preperitoneal
      (TAPP) repair of groin hernias in adult patients. METHOD: From May 2006 to April
      2008, modified TAPP repair for hernia was performed in 403 adult patients with
      groin hernia and 22 with femoral hernia. Indirect hernia sac was treated by high
      ligation of the hernia sac in similar fashion with the management in children,
      while direct or femoral hernia was treated by dissecting the hernia sac. An
      incision was made on the lateral umbilical ligament, and the mesh was stapled and
      covered completely by the peritoneum of the lateral umbilical ligament, followed
      by fixation of the mesh with stapling and absorbable sutures. RESULTS: All the
      operations were accomplished successfully with the operating time from 20 to 30
      min for unilateral hemioplasty and the blood loss volume was 4-5 ml. Two patients
      developed scrotal edema and three showed scrotal seroma. No hernia recurrence was
      found in follow-up for 2-22 months. The patients complained of no intestinal
      obstruction symptoms including traction pain, abdominal pain, or nausea or
      urinary bladder stimulation symptoms. CONCLUSIONS: Modified TAPP repair of groin
      hernias requires simple operation and produces reliable effect, and is therefore
      of clinical values for wide application.

PMID- 19114378
TI  - American College Health Association annual Pap test and sexually transmitted
      infection survey: 2006.
AB  - OBJECTIVE: The authors describe the cervical cytology and sexually transmitted
      infection (STI) testing patterns of US college health centers. PARTICIPANTS AND
      METHODS: A total of 128 self-selected US college health centers-representing more
      than 2 million college students-completed an online survey during February and
      March 2007. RESULTS: Almost 13% of cervical cytology results were abnormal; most
      of these were atypical squamous cells of undetermined significance and low-grade
      squamous intraepithelial lesions. In women, 2.9% of chlamydia tests and 0.4% of
      gonorrhea tests were positive. Human immunodeficiency virus (HIV) and syphilis
      tests were positive in 0.1% and 0.3% of students tested, respectively. Herpes
      simplex virus type 1 (HSV-1) accounted for 59.9% of genital herpes infections.
      CONCLUSIONS: College health centers are important sources for Pap and STI test
      data. Pap tests frequently yield low-grade abnormalities, and screening tests for
      chlamydia and especially gonorrhea are infrequently positive. Rates of HIV and
      syphilis in this population are low, raising concerns about positive predictive
      value when screening low-risk students. A majority of genital herpes infections
      are caused by HSV-1.

PMID- 19114379
TI  - Sociodemographic and psychobehavioral characteristics of US college students who
      abstain from alcohol.
AB  - OBJECTIVE: The authors examined the sociodemographics and psychobehavioral
      characteristics of undergraduate US college students who abstain from alcohol.
      PARTICIPANTS: The respondents were 5,210 undergraduates from 32 colleges and
      universities. METHODS: A survey was mailed to 300 randomly selected students per
      institution (spring 2000 or 2001). The response rate was 56.2%. RESULTS: Overall,
      20.5% of the students abstained. Predictors of abstention included the student's
      own negative attitude toward alcohol use; perception of friends' alcohol
      attitudes; male gender; being under age 21; abstaining in high school; non-Greek
      member or pledge; nonathlete; nonsmoker; non-marijuana user; participant in a
      religious group; working either 0 or 10+ hours per week for salary; having a
      mother who abstains; and having a close friend who abstains. CONCLUSION:
      Additional research on abstainers is warranted. Campus-based prevention programs
      should be grounded in a better understanding of how motives not to drink are
      developed and sustained in high school and college.

PMID- 19114380
TI  - Difference in condom use among sexually active males at historically black
      colleges and universities.
AB  - Black men who have sex with men (MSM) and black men who have sex with both men
      and women (MSMW) may not perceive themselves to be part of the larger gay
      community and hence may not heed prevention messages aimed at the community.
      OBJECTIVE AND PARTICIPANTS: To better understand the participants behaviors, the
      authors examined differences in condom use between black MSM/W (including MSM and
      MSMW) and men who have sex with women (MSW) at historically black colleges and
      universities (HBCUs). METHODS: A paper-and-pencil questionnaire survey
      investigated sexual behaviors of 1,865 freshmen from 35 HBCUs during the 2001
      2002 school year. RESULTS: MSM/W were about 0.37 times less likely to always use
      condoms compared with MSW (adjusted odds ratio = 0.63, 95% confidence interval =
      0.42-0.95). Sexual behavior, age at survey, total family income, and religion
      were also associated with condom use. CONCLUSIONS: These findings offer new
      directions for sexually transmitted disease and HIV prevention aimed at a highly
      marginalized population that remains at high risk for infection.

PMID- 19114381
TI  - Stalking victimization among college women and subsequent help-seeking behaviors.
AB  - OBJECTIVE: The authors examined the incidence of stalking victimization and
      subsequent help-seeking behaviors among college women. PARTICIPANTS AND METHODS:
      A stratified random sample of college women (N = 391) completed an anonymous
      Internet-based questionnaire in spring 2006. RESULTS: One-fifth of women reported
      stalking victimization while enrolled at their current institution. Individuals
      known by victims, such as the following, were most commonly reported as stalkers:
      acquaintances (48.7%), classmates (37.2%), and boyfriends or ex-boyfriends
      (34.6%). Approximately half of the women reporting stalking victimization
      acknowledged not seeking help from anyone in relation to these incidents. Of
      those seeking some sort of help, most sought assistance from friends (90.2%),
      parents (29.3%), residence hall advisors (12.2%), or police (7.3%). CONCLUSION:
      Comparing their findings to a national study of college women, the authors report
      that being watched, followed or spied on, and sent unsolicited emails are
      stalking behaviors on the rise. They present implications for college health and
      future directions for research.

PMID- 19114382
TI  - Associations between physical activity and reduced rates of hopelessness,
      depression, and suicidal behavior among college students.
AB  - OBJECTIVE: The authors explored associations among types of physical activity and
      hopelessness, depression, and suicidal behavior among college students.
      PARTICIPANTS: Participants included 43,499 college students aged 18 to 25 who
      completed the 2005 National College Health Assessment conducted by the American
      College Health Association. METHODS: The authors used logistic regression
      modeling to compare the odds of experiencing hopelessness, depression, and
      suicidal behavior in students who engaged in various levels of aerobic and
      strength or toning activity with students who did not perform these activities.
      RESULTS: Men and women who engaged in some physical activity each week
      demonstrated a reduced risk of hopelessness, depression, and suicidal behavior
      compared with their inactive counterparts. CONCLUSIONS: This study provides
      empirical evidence that establishes the association between physical activity,
      especially aerobic activity, and reduced risk of hopelessness, depression, and
      suicidal behavior among college students.

PMID- 19114383
TI  - Randomized controlled trial examining the effectiveness of a tailored self-help
      smoking-cessation intervention for postsecondary smokers.
AB  - OBJECTIVE: Between September 2002 and February 2003, the authors assessed the
      effectiveness of a new, age-tailored, self-help smoking-cessation program for
      college students. PARTICIPANTS: College student smokers (N = 216) from 6 Ontario
      universities participated. METHODS: The researchers used a randomized controlled
      trial with a 3-month telephone follow-up. Interventions included a new program
      (Smoke|Quit), the Canadian Cancer Society's self-help program, and a usual care
      quit kit. RESULTS: Intention-to-treat analysis of 7-day point prevalence
      cessation revealed quit rates of 11.4% for Smoke|Quit, 2.9% for the Cancer
      Society's program, and 5.6% for the usual care intervention (p < .05). Among
      nonquitters, 46.5% had made a quit attempt, and weekly consumption decreased from
      54.01 to 42.08 cigarettes (p < .001) with no differences across interventions.
      CONCLUSIONS: Making tailored, self-help programs widely available on campus may
      be an effective way to provide smoking-cessation support to a large segment of
      the young adult population.

PMID- 19114384
TI  - Impact of an online alcohol education course on behavior and harm for incoming
      first-year college students: short-term evaluation of a randomized trial.
AB  - OBJECTIVE: The authors assessed short-term effectiveness of a Web-based alcohol
      education program on entering freshmen. PARTICIPANTS: 3,216 incoming first-year
      students were randomized to a control or intervention group. METHODS: Controls
      completed a survey and knowledge test the summer before college; 4 to 6 weeks
      after arrival on campus, they completed a follow-up survey of behaviors and harms
      followed by an invitation to complete the online course. Intervention students
      completed the precourse survey and test, the online course, and final exam prior
      to coming to campus. This was followed by a survey 4 to 6 weeks after arrival on
      campus. RESULTS: Although the intervention group showed significantly higher
      alcohol-related postcourse knowledge compared to the control group, protective
      behavior, risk-related behavior, high-risk drinking, and alcohol-related harm did
      not favor the intervention group, with the sole exception of playing drinking
      games. CONCLUSIONS: Alcohol knowledge alone was insufficient to mitigate alcohol
      related high-risk behaviors in this student population.

PMID- 19114385
TI  - An integrated approach to addressing addiction and depression in college
      students.
AB  - The authors present an integrated, interdisciplinary approach to address the
      problem of increasing student mental health issues on college campuses. The model
      uses addiction and depression as lenses into the problem and links residence life
      and academic and community internship experiences. The project has a positive
      impact on student attitudes and actions and strengthens and broadens the campus
      network required to ensure optimal student mental health.

PMID- 19114386
TI  - Providing student health services at sea: a survey of chief complaints onboard a
      maritime academy training ship.
AB  - OBJECTIVE: The authors describe the epidemiology of infirmary chief complaints
      aboard a collegiate maritime training ship. PARTICIPANTS: They assessed patients
      (N = 646 visits) evaluated by the USTS Enterprise medical department during a 44
      day sea term from January to February 2007. METHODS: The authors conducted a
      retrospective chart review of infirmary use and extracted information on age,
      sex, rank, chief complaints, and frequency of visits. RESULTS: Overall, 646
      visits were made. The most common complaints were dermatologic (30.1%): rash,
      skin infection, laceration, and sunburn. Together, ear, nose, and throat and
      dermatologic complaints accounted for 57.6% of all visits. Work-related
      complaints accounted for 12.5% of recorded visits. Compared with the ship
      population, senior and female cadets had more visits than the average. Port
      departure days were typically the busiest. CONCLUSIONS: Among healthy, college
      aged cadets at sea, typical primary care constitute comprise the majority of
      visits.

PMID- 19114387
TI  - Exploring the climate for overweight and obese students in a student health
      setting.
AB  - Attitudes and beliefs of health care providers, in conjunction with a
      nonthreatening physical environment, are important components in establishing a
      constructive and supportive climate for care of overweight and obese students.
      OBJECTIVE: The authors explored providers' attitudes about obesity and assessed
      the physical environment in a student health clinic to identify areas that may be
      detrimental to the care of overweight and obese students. PARTICIPANTS: Eighteen
      direct care providers participated in the project. METHODS: The authors conducted
      focus groups with direct care providers and assessed their experiences and
      perceived challenges in working with overweight and obese students. The authors
      also conducted a walk-through assessment of the physical environment. RESULTS:
      Direct care providers expressed discomfort in deciding how and when to discuss
      weight with students. The authors found that elements of the physical environment
      could present barriers to care for overweight and obese students. CONCLUSIONS:
      The authors make recommendations for improving the health care climate for
      overweight and obese students.

PMID- 19114388
TI  - Alcohol consumption and risk of type 2 diabetes mellitus in Japanese: a
      systematic review.
AB  - OBJECTIVE: To evaluate the association between alcohol consumption and the risk
      for type 2 diabetes (DM) in Japanese. METHODS: We searched the MEDLINE data base
      with the key words 'alcohol intake' (or 'alcohol consumption') and 'Japanese'
      cross-linked with 'diabetes mellitus' (or 'impaired glucose tolerance'). The
      reports we sought were restricted to prospective cohort studies, randomized
      controlled trials, meta-analyses and systematic reviews. Computerized and hand
      searches were conducted in June 2007. RESULTS: Seven prospective cohort studies
      were adopted. We previously reported that in lean Japanese men (BMI < or =22.0
      kg/m2), moderate to heavy alcohol intake is a risk factor for diabetes. One study
      found heavy alcohol intake to be associated with an increased risk in low-BMI men
      while moderate alcohol intake was associated with a reduced risk in higher-BMI
      men. Another study suggested daily alcohol consumption to be a risk factor in low
      BMI participants, while being protective in middle-BMI participants. Yet another
      study demonstrated a U-shaped association between alcohol consumption and the
      risk of diabetes in men. Three other studies, which did not divide the subjects
      in terms of BMI values, indicated alcohol intake to be an increased risk for
      diabetes, two being in men and one being in women, respectively. CONCLUSION: For
      a large number of Japanese men who have relatively low BMI, alcohol intake is an
      established risk factor for diabetes.

PMID- 19114389
TI  - Effect of omega 3 and omega 6 fatty acid intakes from diet and supplements on
      plasma fatty acid levels in the first 3 years of life.
AB  - BACKGROUND: The optimal method for conducting omega (n-)3 polyunsaturated fatty
      acid (PUFA) supplementation trials in children is unknown. AIM: To assess the
      impact of n-3 and n-6 PUFA intake from the background diet on plasma levels of n
      3 and n-6 PUFA in children aged 0-3 years, with and without n-3 supplementation.
      METHODS: Subjects were randomised antenatally to receive either n-3 PUFA
      supplements and low n-6 PUFA cooking oils and spreads or a control intervention,
      designed to maintain usual fatty acid intake. Dietary intake was assessed at 18
      months by 3-day weighed food record and at 3 years by food frequency
      questionnaire. Plasma phospholipids were measured at both time points.
      Associations were tested by regression. RESULTS: N-3 PUFA intake from background
      diet did not significantly affect plasma n-3 levels. In contrast, n-6 PUFA intake
      in background diet was positively related to plasma n-6 levels in both study
      groups. In addition, n-6 PUFA intake from diet was negatively associated with
      plasma n-3 levels at 18 months and 3 years (-0.16%/g n-6 intake, 95%CI -0.29 to 
      0.03 and -0.05%/g n-6 intake, 95%CI -0.09 to -0.01, respectively) in the active
      group, but not in the control group. CONCLUSION: Interventions intending to
      increase plasma n-3 PUFA in children by n-3 supplementation should also minimise
      n-6 PUFA intake in the background diet.

PMID- 19114390
TI  - Dietary sources of aldose reductase inhibitors: prospects for alleviating
      diabetic complications.
AB  - Activation of polyol pathway due to increased aldose reductase activity is one of
      the several mechanisms that have been implicated in the development of various
      secondary complications of diabetes. Though numerous synthetic aldose reductase
      inhibitors have been tested, these have not been very successful clinically.
      Therefore, a number of common plant/ natural products used in Indian culinary
      have been evaluated for their aldose reductase inhibitory potential in the
      present study. The aqueous extracts of 22 plant-derived materials were prepared
      and evaluated for the inhibitory property against rat lens and human recombinant
      aldose reductase. Specificity of these extracts towards aldose reductase was
      established by testing their ability to inhibit a closely related enzyme viz,
      aldehyde reductase. The ex vivo incubation of erythrocytes in high glucose
      containing medium was used to underscore the significance in terms of prevention
      of intracellular sorbitol accumulation. Among the 22 dietary sources tested, 10
      showed considerable inhibitory potential against both rat lens and human
      recombinant aldose reductase. Prominent inhibitory property was found in spinach,
      cumin, fennel, lemon, basil and black pepper with an approximate IC50 of 0.2
      mg/mL with an excellent selectivity towards aldose reductase. As against this, 10
      to 20 times higher concentrations were required for 50% inhibition of aldehyde
      reductase. Reduction in the accumulation of intracellular sorbitol by the dietary
      extracts further substantiated their in vivo efficacy. The findings reported here
      indicate the scope of adapting life-style modifications in the form of inclusion
      of certain common sources in the diet for the management of diabetic
      complications.

PMID- 19114391
TI  - Nutrient adequacy and food group consumption of Filipino novices and religious
      sisters over a nine month period.
AB  - Rice is commonly consumed in the Philippines; however the contribution of other
      foods to the diet is not well defined. Our aim was to determine the nutrient
      intake and food group intake of Philippine nuns and compare their intakes to the
      current estimated average requirements (EAR), and food-based recommendations,
      respectively, and assess any differences in nutrient adequacy and energy intakes
      between body mass index (BMI) categories. Body weight was assessed at baseline
      and at nine months; three-day weighed food intakes were recorded once every
      fortnight (n=187). At baseline, the mean (SD) age and BMI of the women was: 25.0
      (4.6) years and 21.8 (17.3) kg/m2, respectively. Over the nine months, women with
      an underweight (n=46;<18.5 kg/m2) and acceptable BMI (n=132; 18.5-25 kg/m2) lost
      5.0 kg (p=0.005) and 1.5 kg (p=0.047), respectively, whereas overweight women
      maintained their weight. Irrespective of BMI, 98% of women consumed less than the
      adequate intake for calcium, and no one met the folate EAR. The intake of all
      food groups (e.g., rice, vegetables, fruit, meat, dairy) was lower than food
      based recommendations. It is evident that the nutrient density of the Philippine
      diet is poor. In order to meet nutrient requirements, it is recommended that all
      women increase intake of fruits, vegetables, fish, meat and dairy products, to
      reduce risk of micronutrient deficiencies. For the overweight women, these
      nutrient dense foods also are recommended, however it is important that they be
      substituted for energy dense foods to promote weight loss and prevent weight
      gain.

PMID- 19114392
TI  - Comparison of clinical body composition methods in people taking weight-inducing
      atypical antipsychotic medications.
AB  - The purpose of this study was to compare the accuracy of clinical methods to
      estimate body fat (%BF) in people who take weight-inducing atypical antipsychotic
      medications. Forty-seven people (35 males, 12 females) with previously diagnosed
      psychotic illness who had been taking atypical antipsychotic medications for more
      than 6 months took part in this study. Percentage body fat was estimated using
      bioelectrical impedance analysis (BIA) and anthropometry from previously
      published prediction equations and compared with that measured using the
      deuterium dilution technique which served as the criterion measure. Bland-Altman
      analyses were used to assess the agreement between measures. In the males, %BF
      determined using BIA with the Lukaski equation was the only clinical method with
      mean differences that were not significant from criterion values. While in the
      females, %BF determined from BMI was the only method that was significantly
      different from the criterion values. All of the methods of estimating %BF except
      Watson equations provided consistent estimates across the weight range.
      Therefore, this study suggests that in a group of people who predominantly had
      schizophrenia and were taking atypical antipsychotic medications, BIA using the
      equation of Lukaski was the best indicator of %BF, although on an individual
      basis the accuracy was poor. BMI underestimated %BF to a greater significant
      extent than BIA. The use of BIA rather than BMI may provide a better indicator of
      adiposity in people who take weight inducing antipsychotic medications.

PMID- 19114393
TI  - Chronic energy deficiency and its association with dietary factors in adults of
      drought affected desert areas of Western Rajasthan, India.
AB  - OBJECTIVE: To asses the impact of drought on nutritional status of adults of a
      rural population in desert area. DESIGN: Threestage sampling technique. SETTING:
      24 villages belonging to 6 tehsils (sub units of district) of Jodhpur district, a
      drought affected desert district of Western Rajasthan, in 2003. SUBJECTS: 1540
      adults were examined for their anthropometry, dietary intake and nutritional
      deficiency signs. RESULTS: Overall chronic energy deficiency (CED) was found high
      (42.7 %). Severe CED was 10.7 percent, significantly higher in males than
      females. Regarding vitamin A deficiency, overall prevalence of Bitot spot and
      night blindness was 1.8 and 0.2 percent respectively, higher in females than
      males. Regarding vitamin B complex deficiency, angular stomatitis, cheliosis, and
      glossitis was 1.0, 2.6 and 5.4 percent. Anemia was 35.6 percent. Overall mean
      calorie and protein intake deficit was very high (38 and 16.4 %). The comparison
      of present drought results with earlier studies in desert normal and desert
      drought conditions showed higher deficiencies of calories and proteins in their
      diet. CONCLUSIONS: Severity of malnutrition is critical as CED was more than the
      cut-off point of 40 percent stated by World Health Organization. Vitamin A and B
      complex deficiencies, anemia, protein calorie malnutrition along with deficit in
      calories and proteins in their diet were higher in comparison to non desert
      areas, which may be due to the harsh environmental conditions in desert areas.
      Efforts should be made to incorporate intervention measures to ensure the supply
      of adequate calories and proteins to all age groups.

PMID- 19114394
TI  - Body composition: validity of segmental bioelectrical impedance analysis.
AB  - Bioelectrical impedance analysis (BIA) measures the impedance associated with
      passage of an alternating current through the body which is proportional to total
      body water (TBW) and therefore can provide expedient estimates of body
      composition. However, little validity information is available for commercially
      available bathroom scale type devices which perform whole body estimates from
      segmental (lower limb) measurements. This study therefore compared body
      composition estimates between a commercially available segmental BIA device
      (Tanita BC-532) and four compartment criterion values. Body composition of nine
      males and nine females (mean +/- SD: 37.7 +/- 18.7 yr; 170.7 +/- 5.3 cm; 68.38 +/
      9.7 kg) was determined via BIA and a four compartment model incorporating
      measures of body density, TBW and bone mineral mass. While the mean %BF and fat
      free mass (FFM) values for both methods were not significantly different,
      considerable intra-individual differences were observed. BIA values varied from
      the four compartment values by -3.0 to 4.4 %BF and -3.3 to 1.9 kg FFM. The BIA
      estimates of TBW were significantly different from the criterion measures and
      intraindividual differences displayed a large range (-0.6 to 3.6 kg). Significant
      underestimations of TBW via BIA are concerning given that this is the parameter
      initially established by this method. Furthermore, the BIA data resulted in a FFM
      hydration value of 68.5% which was significantly (p<0.001) lower than the four
      compartment value of 72.0%. In conclusion, the BIA device tested displayed poor
      individual accuracy for the estimation of body composition compared with a four
      compartment criterion method.

PMID- 19114395
TI  - Prevalence of overweight and obesity amongst school children in Delhi, India.
AB  - Obesity has emerged as an epidemic worldwide. The present study was conducted to
      assess the prevalence of overweight and obesity amongst children in the age group
      of 5-18 years belonging to low, middle and high income group in National Capital
      Territory NCT of Delhi. A total of 16,595 children (LIG 5087, MIG 5134 and HIG
      6368) were covered in the present study. Overweight and obesity were assessed
      using Body Mass Index (BMI) and Triceps Skin Fold Thickness (TSFT) utilizing age
      and sex specific cut off points. Considering the BMI cut off points, the
      prevalence of obesity and overweight in Low Income Group (LIG) school children
      was 0.1 and 2.7 percent respectively, amongst Middle Income Group (MIG) school
      children it was 0.6 and 6.5 percent and in High Income Group (HIG) school
      children was 6.8 and 15.3 percent respectively (p<0001). With regard to the TSFT
      criteria, the prevalence of obesity and overweight in LIG school children was 1.2
      and 2.4 percent, amongst MIG school children it was 2.5 and 4.9 percent and in
      children belonging to HIG schools was 9.3 and 13.1 percent respectively
      (p<0.001). The present study documented that the prevalence of overweight and
      obesity was higher in the HIG children as compared to the MIG and the LIG for all
      age groups, highlighting the possible role of change in the dietary pattern and
      physical activities with increase in income levels.

PMID- 19114396
TI  - Parental perception of their children's weight status, and its association with
      their nutrition and obesity knowledge.
AB  - BACKGROUND: Worldwide the prevalence of overweight and obesity in children is
      escalating. Parents' recognition of overweight or obesity in their own children
      is very important for a successful intervention in these children. This study
      examined parental perception of their children's weight status, and its
      association with their knowledge on nutrition and obesity. MATERIALS AND METHODS:
      This was a cross sectional study of parents with children aged 9 to 12 years, in
      a primary school of Kuala Lumpur. Parents responded to a self-administered
      questionnaire which contains parental perception of their child weight status as
      well as knowledge on nutrition and obesity. The parents' perception of the
      children's weight status was then compared with the actual measured weight
      status. RESULTS: There were 204 parents who participated in the study. Parents
      were found to underestimate their child weight status and 38.2% were inaccurate
      in their perception. The mean score of knowledge on nutrition and obesity was
      78.5+/-14.4; and this did not associate with the accuracy of their perception on
      the child weight status. Parents showed inadequate knowledge in food pyramid and
      preparation of low fat meals. CONCLUSION: The Malaysian Health Campaigns had
      resulted in overall good knowledge on nutrition and obesity in the parents except
      in few domains. However, this was insufficient to make the parents recognize the
      growing overweight and obesity problem in their children.

PMID- 19114397
TI  - Regional clustering of anthropometric dimensions of primary school children in
      rural and suburban Vietnam.
AB  - Nutrition transition is one of the driving forces of the upcoming global epidemic
      of diabetes mellitus and cardiovascular diseases. We hypothesized that in
      previously deprived rapidly changing regions, the progress of the obesity
      epidemic is clustered per community and that screening with anthropometric school
      surveys can detect the negative effects of the nutrition transition in its early
      stages. In 16 different rural and urban communities in Binh Thuan Province,
      southern Vietnam, anthropometric surveys were conducted in local primary schools.
      Anthropometry of 2613 children showed a significant difference of the prevalence
      of wasting, stunting, and overweight between urban and rural communities. During
      the transition from high stunting rates to overweight, communities pass through
      an episode with dual burden of both conditions at different pace. Anthropometry
      of primary school children can reveal inter-community differences and identify
      the early stages of the nutrition transition.

PMID- 19114398
TI  - Efficacy of modified WHO feeding protocol for management of severe malnutrition
      in children: a pilot study from a teaching hospital in New Delhi, India.
AB  - AIM: To assess the efficacy of modified World Health Organization (WHO) feeding
      protocol for severe malnutrition. SETTING: Prospective observational study
      conducted in the nutritional rehabilitation center of a tertiary care teaching
      hospital of New Delhi, India over four months period from August to November
      2007. METHODS: 25 children with severe malnutrition (age 6 months to 5 years)
      were recruited. All children were treated according to Indian Academy of
      Pediatrics modified WHO guidelines. Daily weight gain and improvement in the
      clinical status was assessed. Children were followed up at day 15, day 30 and day
      45 after discharge or when a new problem emerged. RESULTS: Weight-for-age z score
      (WAZ) at admission was -4.82+/-0.96, weight-for-height z score (WHZ) was -5.0+/
      0.7, height-for-age z-score (HAZ) was -2.55+/-1.65. All children had diarrhea on
      admission, two had pneumonia in addition, and one each had otitis, sepsis and
      hepatitis in addition to diarrhea. The mean duration of admission was 8.32+/-2.87
      days. At discharge the mean WAZ was -4.15+/-0.92 and mean WHZ, -3.91+/-0.61 (p
      value highly significant). Follow up at day 15, 30 and 45 showed significant
      improvement in WAZ and WHZ. CONCLUSIONS: Following modified WHO guidelines is
      feasible, efficacious and cost effective in resource-limited settings. Early
      discharge of patients is possible with no complications or mortality.

PMID- 19114399
TI  - Relationship between dietary fat and fish intake and the prevalence of atopic
      eczema in pregnant Japanese females: baseline data from the Osaka Maternal and
      Child Health Study.
AB  - Dietary factors may be important in the development of atopic eczema. It remains
      controversial whether n-3 polyunsaturated fatty acid intake is preventive against
      allergic disorders and whether n-6 polyunsaturated fatty acid intake increases
      the risk of allergic disorders. The current cross-sectional study examined the
      association between intake of fatty acids and foods high in fatty acids and the
      prevalence of atopic eczema. Study subjects were 1002 pregnant Japanese females.
      Current atopic eczema and atopic eczema after age 18 were defined as present if
      subjects had been treated with medications at some time in the previous 12 months
      and after reaching the age of 18, respectively. Information on dietary factors
      was collected using a validated self-administered diet history questionnaire.
      Docosahexaenoic acid intake was statistically significantly related to a
      decreased prevalence of atopic eczema after age 18 and current atopic eczema.
      Inverse dose-response relationships with regard to consumption of n-3
      polyunsaturated fatty acids, eicosapentaenoic acid, and fish and the ratio of n-3
      to n-6 polyunsaturated fatty acids with atopic eczema were not observed although
      these dietary variables in the second tertile were inversely significantly
      associated with atopic eczema after age 18. Intake of total fat, saturated fatty
      acids, monounsaturated fatty acids, n-6 polyunsaturated fatty acids, cholesterol,
      meat, eggs, or dairy products was not related to either of the outcomes for
      atopic eczema. Docosahexaenoic acid intake may be associated with a reduced
      prevalence of atopic eczema in pregnant Japanese females.

PMID- 19114400
TI  - Iodine deficiency disorders in Bangladesh, 2004-05: ten years of iodized salt
      intervention brings remarkable achievement in lowering goitre and iodine
      deficiency among children and women.
AB  - A survey was conducted to monitor the current status of iodine deficiency
      disorders in children aged 6-12 years and women aged 15-44 years in Bangladesh as
      measured by goitre prevalence and urinary iodine excretion. Conducted between
      September 2004 and March 2005, the survey followed a stratified multistage
      cluster sampling design to provide nationally representative data, with self
      weighted rural-urban disaggregation. A total of 7233 children and 6408 women were
      examined for goitre and 4848 urine samples (2447 from children and 2401 from
      women) were analyzed for iodine. In addition, 5321 household salt samples were
      analyzed for iodine. In children, the total goitre rate (TGR) was 6.2%, compared
      to 49.9% in 1993 and the TGR among women was 11.7%, while in 1993 it was 55.6%.
      Prevalence of iodine deficiency (Urinary Iodine Excretion <100 microg/L) was
      33.8% in children and 38.6% in women (compared to 71.0% and 70.2%, respectively
      in 1993). Iodine nutrition status in urban areas was considerably better than in
      rural areas. There was a clear inverse relationship between iodine deficiency and
      the coverage of households using adequately iodized salt (> or =15 ppm). The
      findings of the survey revealed that Bangladesh has achieved a commendable
      progress in reducing goitre rates and iodine deficiency among children and women
      ever since the universal salt iodization programme was instituted 10 years ago.
      However, physiological iodine deficiency still persists among more than one-third
      of children and women, which points to the need for all stakeholders to redouble
      their efforts in achieving universal salt iodization.

PMID- 19114401
TI  - Validity and reproducibility of a food frequency questionnaire designed for
      residents in north China.
AB  - The objective of this study was to evaluate the validity of a Xi'an food
      frequency questionnaire (FFQ) designed for application in an international case
      control colorectal cancer study. The FFQ was administered to 125 participants
      twice over 1-year interval. Four 24-hour dietary recalls (24-HDRs) were conducted
      with the same participants in each season of the year. Comparative validation was
      assessed by comparing the nutrient intakes derived from the 24-HDRs and the FFQ
      2, and reproducibility was estimated by comparing the nutrient intakes from two
      FFQs. In the validation study, the mean deattenuated correlation coefficients for
      nutrients between the 24-HDRs and the FFQ-2 ranged from 0.35 to 0.84 in the
      males. The female results were slightly lower than the male's. The mean
      percentage of classification into the same quartile was 38% for the males and 35%
      for the females. In the reproducibility study, the mean crude correlation
      coefficients between the two FFQs were from 0.41 to 0.68 in the males and from
      0.36 to 0.66 in the females. The newly developed Xi'an FFQ appears to be
      reasonably valid and reliable for most nutrients but would benefit from the
      addition of nutritional supplements and seasonings for assessing dietary intake
      in older persons in Xi'an, China.

PMID- 19114402
TI  - Consumption of guava (Psidium guajava L) and noni (Morinda citrifolia L) may
      protect betel quid-chewing Papua New Guineans against diabetes.
AB  - Rapid increase in the incidence of type 2 diabetes (DM2) in Papua New Guinea,
      coupled with compelling epidemiological evidence supporting a diabetogenic
      association with betel quid (BQ) chewing has lead us to investigate dietary
      strategies that might offer protection from developing DM2. We investigated the
      dietary habits of Kalo residents from coastal Central Province who are avid BQ
      chewers yet have a relatively low incidence of DM2 compared to the ethnically
      similar and adjacent Wanigelans who abstain from BQ yet have an unusually high
      incidence of DM2. In Kalo, guava bud (Psidium guajava L) and noni (Morinda
      citrifolia L) were consumed much more frequently than in Wanigela, whereas the
      inverse was observed for mangrove bean (Bruguiera gymnorrhiza (L) Lam.). These
      plants, along with BQ and its component ingredients areca nut (Areca catechu L)
      and Piper betle L inflorescence, were assessed for their ability to mediate
      insulin-dependent and insulin-independent glucose transport in cultured 3T3-L1
      adipocytes. A dose-dependent inhibition of glucose uptake from methanolic
      extracts of BQ, areca nut and P. betle inflorescence supports previous reports of
      prodiabetic activity. Conversely, guava bud extract displayed significant insulin
      mimetic and potentiating activity. Noni fruit, noni leaf, commercial noni juice
      and mangrove bean all displayed insulin-like activity but had little or no effect
      on insulin action. Habitual intake of guava and noni is proposed to offer better
      protection against DM2 development and/or betel quid diabetogenicity than cooked
      mangrove bean. These findings provide empirical support that DM2 risk reduction
      can be accomplished using traditional foods and medicines.

PMID- 19114403
TI  - Stomach cancer in 67 Chinese counties: evidence of interaction between salt
      consumption and helicobacter pylori infection.
AB  - OBJECTIVE: To examine the interaction between salt-intake and helicobacter pylori
      (H. pylori) infection in the development of stomach cancer in an ecological study
      of 67 Chinese rural counties. METHODS: Stomach cancer mortality data of 67
      counties were derived from a national survey conducted in China between 1986 and
      1988. Information regarding the prevalence of H. pylori infection and urinary
      sodium excretion were collected from the same individuals during a subsequent
      dietary survey in 1989. RESULTS: In these 67 counties, H. pylori prevalence and
      urinary sodium were correlated with stomach cancer mortality, with r=0.31
      (p=0.01) and r=0.28 (p=0.03), respectively. After stratification, the significant
      correlation between H. pylori prevalence and stomach cancer mortality only
      existed in counties with high levels (> or =5.0 mg/mg creatinine/12-hour) of
      urinary sodium (r=0.5; p=0.002). Similarly, the significant correlation between
      urinary sodium and stomach cancer mortality was only presented in counties with
      high (> or =71.6%) H. pylori prevalence (r=0.4; p=0.017). Multivariate regression
      analysis showed results consistent with the correlation analysis. CONCLUSION:
      These findings suggest that there may be an interaction between high salt
      consumption and H .pylori infection in the development of stomach cancer.
      Corroborating data from epidemiological, clinical, and experimental studies are
      needed.

PMID- 19114404
TI  - The association of plasma C-reactive protein levels with anthropometric and lipid
      parameters in elderly Taiwanese.
AB  - C-reactive protein (CRP), a plasma inflammation marker, has been known to play a
      role in the development of cardiovascular diseases. This study aims to evaluate
      the association of CRP with anthropometric and plasma lipid parameters in elderly
      Taiwanese 65 years or older. Data from the Elderly Nutrition and Health Survey in
      Taiwan (1999-2000), a national probability sampling study conducted to gain an
      understanding of the dietary pattern, and nutritional and health status of
      elderly Taiwanese were analyzed. Results showed that in men, CRP was positively
      correlated with age and waist-to-hip ratio (WHR) (both p<0.05) whereas in women,
      CRP was positively correlated with waist and WHR but negatively correlated with
      HDL-C (all p<0.05). Linear regression analysis showed that log CRP was positively
      associated with WHR in both genders (p<0.05) after adjusting for confounders. The
      correlation of CRP with WHR was stronger than that with both waist circumference
      and body mass index (BMI). Log CRP was inversely associated with HDL-C in women,
      but not men. The study suggests that among the anthropometric parameters
      examined, WHR is a stronger predictor for elevated CRP in elderly Taiwanese men
      and women. Whereas low HDL-C is a predictor among the plasma lipid parameters for
      elevated plasma CRP, at least in women. Gender differences exist in the
      association of CRP with anthropometric and lipid parameters.

PMID- 19114405
TI  - Delayed effects of coffee, tea and sucrose on postprandial glycemia in lean,
      young, healthy adults.
AB  - In observational studies, habitual coffee consumption has been linked to a lower
      risk of type 2 diabetes. We hy-pothesized that the mechanism may be related to
      delayed effects on postprandial glycemia. The aim of this study is to investigate
      the glycemic and insulinemic effects of consumption of caffeinated and
      decaffeinated coffee, sweetened and unsweetened, tea and sucrose, 1 h prior to a
      high carbohydrate meal. On separate occasions in random order, lean young healthy
      subjects (n = 8) consumed a potato-based meal 1 hour after consumption of 250 mL
      of black coffee (COF), black coffee sweetened with 10 g of sucrose (COF+SUC),
      decaffeinated coffee (DECAF), black tea (TEA), 10 g sucrose (SUC) or hot water
      (CON). Fingerprick blood samples were taken at regular intervals over 2 h and the
      glucose and insulin responses quantified as area under the curve. Compared to
      CON, COF caused a 28% increase in postprandial glycemia (p = 0.022). In contrast,
      COF+SUC decreased glycemia compared with either COF (-38%, p<0.001) or CON (-20%,
      p = 0.100) but had no effect on insulin responses. DECAF, TEA and SUC had no
      significant effects on postprandial responses. SUC and DECAF reduced the absolute
      glucose concentration at the start of the meal (p<0.01). In conclusion, only
      sweetened coffee significantly reduces postprandial glycemia. This observation
      may explain the paradoxical findings of observational and clinical studies
      relating coffee drinking to diabetes risk.

PMID- 19114406
TI  - Natto and viscous vegetables in a Japanese style meal suppress postprandial
      glucose and insulin responses.
AB  - Naturally viscous vegetables and natto, made by fermenting soybeans, are very
      palatable and considered to be healthy foods in Japan. The objective was to
      assess whether the consumption of natto and viscous vegetables as part of a
      traditional Japanese breakfast based on high-glycemic index white rice affects
      glycemic, insulinemic, lipidemic and satiety responses in healthy subjects.
      Eleven healthy subjects consumed the reference, control and test meals in a
      randomized cross-over design. The test meal, comprising 200 g of boiled white
      rice with viscous meal (50 g natto, 60 g Japanese yams and 40 g okras), and the
      control meal, comprising 200 g of white rice with non-viscous boiled soybeans,
      potatoes and broccoli, contained comparable amounts of carbohydrate, fat, protein
      and fiber. In addition, whiter rice was used as a reference meal. Blood samples
      over 180 min were analyzed for glucose, insulin, non-esterified free fatty acid
      and triacylglyceride. Peak glucose and insulin concentrations after the test meal
      (6.0 mmol/L and 262 pmol/L) were significantly lower than after the control meal
      (6.8 mmol/L and 360 pmol/L). The incremental areas under the curve for glucose
      and insulin over 0-120 min after the test meal were also significantly reduced as
      compared with the control meal (28 and 27%). The consumption of naturally viscous
      vegetables with white rice reduced acute glycemia and insulinemia. This practical
      dietary combination would ensure compliance and favorably alter the risk for
      diabetes and cardiovascular diseases.

PMID- 19114408
TI  - Nutrition leadership training in North-East Asia: an IUNS initiative in
      conjunction with nutrition societies in the region.
AB  - Food for humans is one of the most important of all global issues. It is a
      critical determinant of planetary and individual health, of economic development,
      of how sustainable energy and water supplies are, and its security a powerful
      determinant of peace or conflict. Those who assume leadership for the integrity
      of food and health systems have great responsibility. The IUNS (International
      Union of Nutritional Sciences), regional and national nutrition science and food
      technology organizations have concern about the leadership capacity available and
      required in what are rapidly changing and increasingly demanding circumstances.
      These include persistent poverty and hunger, climate change which threatens the
      sustainability of food production and fragile financial systems which are making
      food less affordable for many. North East Asia (NEA) is a major region for its
      population size, its economic wealth and disparities, its food production, its
      life expectancies among the best and its global reach. In 2008, for those of
      Chinese ancestry and of wider Asian origin, Nutrition Leadership training has
      been conducted in Hangzhou, Shanghai, Seoul and Taiwan (Hsinchu and Zhunan).
      Ninety prospective young leaders participated in all. Several successful early
      career Asian nutrition scientists and professionals served as role models. Senior
      colleagues acted as mentors for groups of 2 or 3. With mentors, the concept of
      leadership has been examined, careers and roles explored, knowledge and skills
      honed for a different future, and plans made to network in mutual support. Early
      feedback indicates that new opportunities have been created and seized.

PMID- 19114407
TI  - Clinical experience with a relatively low carbohydrate, calorie-restricted diet
      improves insulin sensitivity and associated metabolic abnormalities in
      overweight, insulin resistant South Asian Indian women.
AB  - South Asian Indians are at increased risk for cardiovascular disease associated
      with insulin resistance and a dyslipidemia characterized by high triglyceride and
      low high-density lipoprotein cholesterol concentrations. The purpose of this
      study is to determine the effects of a calorie-restricted, relatively low
      carbohydrate diet on weight loss, insulin sensitivity, and associated
      cardiovascular disease risk factors in overweight, insulin resistant, but
      apparently healthy, South Asian Indian women. Twenty-three, overweight, insulin
      resistant, apparently healthy, South Asian Indian women were advised on a calorie
      restricted diet containing 40 percent carbohydrate for 3 months. Change in
      weight, insulin sensitivity (quantified by the steady state plasma glucose
      concentration during the insulin suppression test), and associated cardiovascular
      disease risk factors were measured. Weight fell from 75.5 to 70.5 kg (p<0.001),
      associated with significant decreases in diastolic blood pressure, plasma
      concentrations (mg/dL) of steady state plasma glucose (217 to 176, p<0.001),
      triglycerides (137 to 101, p = 0.003), and glucose (98 to 92, p = 0.005). A
      calorie-restricted diet, moderately lower in carbohydrate, can lead to weight
      loss, decreased insulin resistance, and reduction in several cardiovascular
      disease risk factors in overweight, insulin resistant, apparently healthy, South
      Asian Indian women.

PMID- 19114409
TI  - Changes of metalloproteinases profile in patients with masked hypertension.
AB  - INTRODUCTION: The aim of our study was to investigate whether collagen
      degradation is altered in participants with masked hypertension and whether this
      alteration could be related to disturbances in the matrix metalloproteinases
      plasma concentration and to compare the findings with those participants with
      normal blood pressure levels matched for age, sex, and body mass index. METHODS:
      Twenty-four (11 men, 13 women) participants with masked hypertension [mean age 46
      +/- 7 years and body mass index 25.9 +/- 2.1 kg/m(2) (group A)] and 106 healthy
      normotensives (49 men, 57 women) with normal blood pressure [mean age 44 +/- 6
      years and body mass index 25.5 +/- 2.4 kg/m(2) (group B)]. RESULTS: The plasma
      levels of matrix metalloproteinase-9 were significantly higher, while the levels
      of tissue inhibitors of metalloproteinases-1 and -4 were significantly lower in
      group A compared with group B (matrix metalloproteinase-9: 569 +/- 135 vs. 282 +/
      117 ng/mL, TIMP-1: 169 +/- 42 vs. 230 +/- 37 ng/mL, P < .01, and TIMP-4: 2.1 +/-
      1.3 vs. 4.2 +/- 1.98 ng/mL, P < .04, respectively). CONCLUSIONS: Patients with
      masked hypertension had significantly increased matrix metalloproteinase-9 plasma
      levels and significantly decreased plasma levels of tissue inhibitors of
      metalloproteinases-1 and -4 compared with participants with normal blood
      pressure. These findings need further investigation.

PMID- 19114410
TI  - A biobehavioral model for the study of exercise interventions in cancer-related
      fatigue.
AB  - Cancer-related fatigue (CRF) is a multifactorial, biobehavioral phenomenon
      experienced by the majority of persons with cancer. It has negative consequences
      on the individual's physical functioning and quality of life. An array of
      biological, psychobehavioral, and functional mechanisms contributes to its
      occurrence. A relatively large number of studies have examined the effect of
      physical exercise on CRF over the past few decades. Most of these studies did not
      specifically examine the effect of physical exercise on the biobehavioral
      mechanisms underlying CRF. For the most part, these studies have not been guided
      by a consistent theoretical model. Consequently, the mechanisms by which exercise
      may ameliorate CRF are not fully elucidated. A theoretical model incorporating
      fatigue-related biobehavioral variables that could be affected by physical
      exercise will allow for effective knowledge development in this area and could
      lead to the development and refinement of exercise protocols that specifically
      target these mechanisms. Thus, the purpose of this paper is to present a
      comprehensive theoretical model to guide future research on the effectiveness of
      exercise interventions in CRF. The proposed model incorporates the biological,
      psychobehavioral, and functional variables implicated in the induction of CRF.

PMID- 19114411
TI  - Conceptualizing compensatory responses: implications for treatment and research.
AB  - Many scientists approach the discovery and application of knowledge of
      physiological processes from a reductionistic paradigm. A reductionistic approach
      focuses on treating one or a few key disease-related variables but overlooks the
      interaction of systems and their dependency on one another to produce
      homeostasis. The purposes of this article are to examine the current paradigm
      underlying treatment and its effect on patient outcome and to present an
      alternative perspective for understanding the body's compensatory responses and
      their implications for treatment and research. Chaos theory and nonlinear methods
      are presented as possible ways to conceptualize and explore the complex
      integration of physiological patterns in response to disease, aging, and
      treatment.

PMID- 19114412
TI  - Is shock a key element in the pathology of sudden infant death syndrome (SIDS)?
AB  - In developed countries, sudden infant death syndrome (SIDS) is the most common
      cause of death for infants between 1 month and 1 year of age. The etiology of
      SIDS is likely to be multifactorial, and current paradigms often describe three
      overlapping elements of risk. Those elements are a critical developmental period,
      a vulnerable infant, and one or more exogenous stressors. In the triple-risk
      model, SIDS infants are described as having an underlying vulnerability in
      cardiorespiratory control in the central nervous system during a critical period
      when autonomic control is developing. This vulnerability might affect the
      response to exogenous stressors, including prone sleeping position, hypoxia, and
      increased carbon dioxide. In the common bacterial hypothesis and fatal triangle,
      the focus is on the stressors. In the first, a combination of common respiratory
      infections can cause SIDS in an infant during a developmentally vulnerable
      period. This theory also includes 3 factors of vulnerability: a genetic
      predisposition, a vulnerable developmental age, and infectious stressors. In the
      fatal triangle theory, infection, inflammation, and genetics each play a role in
      triggering a SIDS fatality. From our work in an animal model, we have found that
      rat pups die from a combination of infectious insults during a critical time of
      development. This is exacerbated by perinatal nicotine exposure, a condition
      shown to alter the autonomic response in exposed offspring. We are proposing that
      shock and cardiovascular collapse is a key element that links these theories.

PMID- 19114413
TI  - Lateral hypothalamic-induced alpha-adrenoceptor modulation occurs in a model of
      inflammatory pain in rats.
AB  - Previous work from our lab showed that stimulation of the lateral hypothalamus
      (LH) produces analgesia (antinociception) in a model of thermal nociceptive pain.
      This antinociceptive effect is mediated by alpha2-adrenoceptors in the spinal
      cord dorsal horn. However, a concomitant, opposing hyperalgesic (pro-nociceptive)
      response also occurs, which is mediated by alpha1-adrenoceptors in the dorsal
      horn. Antinociception predominates but is attenuated by the pronociceptive
      response. To determine whether such an effect occurs in a model of inflammatory
      pain, we applied mustard oil (allyl isothiocyanate; 20 microl) to the left ankle
      of female Sprague-Dawley rats. We then stimulated the LH using carbamylcholine
      chloride (carbachol; 125 nmol). The foot withdrawal latencies were measured. Some
      rats received intrathecal alpha-adrenoceptor antagonists to determine whether the
      opposing alpha-adrenoceptor response was present. Mustard oil application
      produced hyperalgesia in the affected paw, while the LH stimulation increased the
      foot withdrawal latencies for the mustard oil paw as compared to the control
      group. Following carbachol microinjection in the LH, WB4101, an alpha1
      adrenoceptor antagonist, produced significantly longer foot withdrawal latencies
      compared to saline controls, while yohimbine, an alpha2-antagonist, decreased the
      foot withdrawal latencies from 10 min postinjection (p < .05). These findings
      support the hypothesis that the LH-induced nociceptive modulation is mediated
      through an alpha-adrenoceptor opposing response in a model of inflammatory pain.

PMID- 19114414
TI  - A feasibility study of valerian extract for sleep disturbance in person with
      arthritis.
AB  - OBJECTIVES: To present a pilot study of valerian to explore issues of feasibility
      and efficacy in studies of sedative herbs for arthritis-related sleep
      disturbance. METHODS: Fifteen persons with arthritis and mild sleep disturbance
      were randomized to receive 600 mg valerian (Valeriana officinalis, n = 7) or
      placebo (n = 8) for five nights. RESULTS: Protocol adherence (dosing and data
      collection) was high. Allocation concealment was successful using a novel
      approach for matching the placebo on the distinctive odor of valerian.
      Nonsignificant differences between the groups were found on all sleep outcomes,
      measured by daily diaries and wrist actigraphy. CONCLUSION: The study methods
      were feasible, except for recruitment issues (addressed in the discussion), and
      may guide the testing of other sedative herbs for persons with arthritis.
      Although efficacy outcomes were inconclusive due to the small sample size of this
      study, recent evidence from larger trials of valerian also does not support its
      efficacy.

PMID- 19114415
TI  - Blood pressure management in acute head injury.
AB  - Head injury remains a major cause of preventable death and serious morbidity in
      young adults. Based on the available evidence, it appears that a cerebral
      perfusion pressure of 50 to 70 mm Hg is generally adequate to ensure cerebral
      oxygen delivery and prevent ischemia. However, evidence suggests that perfusion
      requirements may not only vary across the injured brain but also differ depending
      on the time since injury. Such heterogeneity, both within and between subjects,
      suggests that individualized therapy may be an appropriate treatment strategy.
      Future studies should aim to assess which groups of patients, and what regional
      pathophysiological derangements, may benefit with improvements in functional
      outcome from therapeutic increases or decreases in cerebral perfusion pressure
      beyond these proposed limits. Such functional improvements may be of immense
      importance to patients and require formal neurocognitive assessments to
      discriminate improvements.

PMID- 19114416
TI  - Considerations in caring for the critically ill older patient.
AB  - People over age 65 are the fastest growing segment of the population and account
      for 42% to 52% of the intensive care unit admissions in the United States. There
      are many physiologic changes that occur with aging which can impact on both the
      presentation and management of older patients with critical illness. Older
      patients have an increased risk for the development of sepsis, and age itself
      impacts on outcomes related to sepsis. Delirium is also very prevalent among
      older intensive care unit patients and is associated with adverse outcomes. While
      outcome studies suggest that chronologic age itself is not a risk factor for poor
      outcomes after adjusting for severity of illness, older patients clearly have
      physiologic changes which need to be considered when providing critical care.
      This article will review important physiologic changes of aging, as well as
      sepsis and delirium and outcomes of older ICU patients.

PMID- 19114417
TI  - Evidence-based diagnosis and clinical decision making.
AB  - The application of evidence-based dentistry to diagnosis should result in a
      reduction of errors in decision making. The frequency of errors is dependent not
      only on the accuracy of a diagnostic test for pathology, but also on the prior
      chance of disease being present. If this chance is low and below a certain
      threshold, then, for example, applying a diagnostic test can result in more
      decision errors and therefore inappropriate treatment than omitting to use the
      test. In deciding on the usefulness of a diagnostic test an additional factor to
      take into account is the relative value of the possible health states resulting
      from diagnosis and subsequent therapy. These can be determined by eliciting from
      the patient the numerical values of the possible dental health conditions using a
      visual analogue scale technique. Clinical decision analysis can then be carried
      out to calculate the most appropriate diagnostic strategy for the patient.
      Clinical decision analysis is starting to influence the development of guidelines
      for the diagnostic use of radiographs although its application in dentistry needs
      further refinement and development.

PMID- 19114418
TI  - Correlation of darkening of impacted mandibular third molar root on digital
      panoramic images with cone beam computed tomography findings.
AB  - OBJECTIVES: Darkening of the lower third molar root on panoramic images is known
      to indicate an intimate relationship between the root and mandibular canal. The
      objective of this study was to investigate the anatomical relationship between
      the third molar root and its surrounding structures that leads to this panoramic
      finding. METHODS: Imaging findings of 253 impacted lower third molars examined by
      both digital panoramic radiography and cone beam CT were reviewed. Panoramic
      images were evaluated to detect the presence or absence of darkening of the root
      where the mandibular canal was superimposed. Cone beam CT images were evaluated
      for the presence or absence of the following two findings: (1) grooving of the
      root and (2) thinning or perforation of the cortical plate by the root. The
      correlation between the panoramic and cone beam CT findings was examined using
      logistic regression analysis. RESULTS: 80 (32%) third molars showed a panoramic
      finding of darkening of the root. Between cone beam CT findings, cortical
      thinning or perforation alone was significantly correlated with this panoramic
      finding (80%, P < 0.001). CONCLUSIONS: The panoramic finding of mandibular third
      molar root darkening was considered to reflect cortical thinning or perforation
      rather than grooving of the root.

PMID- 19114419
TI  - Correlation between histopathological image and radiographic image pattern in
      fibro-osseous lesions in relation to bone complexity and distribution.
AB  - OBJECTIVES: This study examined correlations between radiographic patterns and
      the shape of osteoid tissue formations, as determined histopathologically.
      METHODS: 20 cases of fibro-osseous lesions were investigated, comprising 5
      radiographic patterns: focal (n = 3), target (n = 6), lucent (n = 4),
      calcification (n = 3) and multiconfluent (n = 4). Histopathological images in the
      central area of a full-section specimen were transformed into binary images and
      then into 8-bit scale images. Bone complexity and density of bone distribution
      were calculated and compared between patterns. RESULTS: Bone complexity score was
      7384.64 for lucent, 2029.85 for focal, 2713.40 for multiconfluent, 8388.63 for
      calcification and 1364.27 for target pattern. The results could be broadly
      separated into two types: small (target, focal and multiconfluent patterns), and
      large (lucent and calcification patterns). Density of bone distribution was
      relatively low in all areas for lucent and calcification patterns, and high for
      focal, multiconfluent and target patterns. No significant differences in bone
      complexity or density of bone distribution were seen between individual patterns.
      CONCLUSIONS: Correlations appear to exist between image patterns from radiography
      and the shape of osteoid tissue on histopathology, but reorganization of the five
      patterns may be warranted.

PMID- 19114420
TI  - Ultrasonography and Doppler ultrasonography in the evaluation of intraosseous
      lesions of the jaws.
AB  - OBJECTIVES: To evaluate the efficacy of ultrasonography and colour and power
      Doppler ultrasonography for diagnosis of intraosseous lesions of the jaws and to
      correlate the contents of the lesion with the histological findings. METHODS:
      This study included 20 patients referred to the oral surgery clinic for
      treatment. All patients had intraosseous jaw lesions in the maxilla or mandible.
      Ultrasonographic examinations were performed and, according to the
      ultrasonography findings, the jaw lesions were classified into three groups:
      cystic, semisolid and solid. Additionally, colour and power Doppler
      ultrasonography examinations were performed to evaluate blood flow in all
      patients. After the ultrasonography examination, the patients underwent surgical
      treatment. The correlation between ultrasonography and Doppler ultrasonography
      findings of the lesions and histological findings was investigated. RESULTS: 22
      lesions were identified in 20 patients. Of the five lesions with histological
      findings of inflammatory granulation tissue, ultrasonography identified four of
      them that showed a solid appearance. Vascularization was detected in both
      internal and external areas of these lesions with colour and power Doppler
      ultrasonography. Of the 17 odontogenic cystic lesions, the ultrasonography
      examination showed a simple cystic appearance in 5 lesions, a complex cystic
      appearance in 3 lesions, a semisolid appearance in 6 lesions and a solid
      appearance in 1 lesion. Two lesions were inconclusive on ultrasonographic
      examination. CONCLUSIONS: Ultrasonography can provide accurate information on the
      content of intraosseous lesions of the jaws before any surgical procedure.
      Additionally, Doppler ultrasound can show vascularization of the lesion. However,
      there was no correlation between the ultrasound findings and the definitive
      histological diagnosis.

PMID- 19114421
TI  - Intraoperative computed tomography and automated registration for image-guided
      cranial surgery.
AB  - OBJECTIVES: Two key problems for the use of navigation systems in image-guided
      surgery are accurate patient-to-image registration and the fact that with ongoing
      surgery the patient's anatomy is altered while the image data remains unchanged.
      A system for intraoperative CT imaging and fully automated registration of this
      image addresses both problems. It had been evaluated successfully in phantom
      studies. In this clinical study, we assessed the impact of the system on
      intraoperative workflow and registration accuracy in everyday patient care.
      METHODS: In ten patients who underwent image-guided surgery, CT image data were
      acquired intraoperatively and were automatically registered in the navigation
      system. Registration accuracy and surgical outcome were assessed clinically. In
      six of these patients, a maxillary splint with markers had been inserted to cross
      check registration accuracy. The target registration error of these markers was
      measured. RESULTS: In all cases, registration accuracy was clinically sufficient
      and the surgical task could be performed successfully. In those cases where a
      maxillary template with target markers was attached for additional control of the
      registration accuracy, the target registration error was always better than 2 mm.
      Automated registration reduced the intraoperative registration time considerably
      and partially compensated for the time needed to perform the image data
      acquisition. CONCLUSIONS: Intraoperative CT imaging and automated registration
      successfully address the two key problems of image-guided surgery. The method is
      robust and accurate and proved its usability in everyday patient care.

PMID- 19114422
TI  - Influence of prednisolone-induced osteoporosis on bone mass and bone quality of
      the mandible in rats.
AB  - OBJECTIVES: The aim of this study was to clarify the effects of steroid treatment
      on the mandible. METHODS: We divided 24 male Fisher rats, aged 10 weeks, into 2
      groups: a control group (n = 11) and a prednisolone (Pred) treatment group (n =
      13). The dose for the Pred group was 40 mg kg(-1) and was administered orally
      three times per week for 8 weeks. At the end of the experiment, we measured bone
      mass, bone strength and trabecular structure of the mandible and femur. RESULTS:
      Pred treatment decreased cortical bone mineral content (BMC), cortical thickness,
      stress/strain index and tissue volume of the mandible. However, there were no
      marked changes in trabecular structure parameters. A strong correlation was seen
      between mandibular and femoral cortical BMC (r = 0.71). CONCLUSIONS: These
      findings suggest that steroid treatment decreases the cortical BMC, bone area and
      bone strength of the mandible.

PMID- 19114423
TI  - How many times can we use a phosphor plate? A preliminary study.
AB  - OBJECTIVES: Digital radiography has become a useful tool in daily dental practice
      due to the advances in imaging technologies. Charge coupled devices (CCDs) and
      photostimulable phosphor plates (PSPs) are currently in use for dental imaging;
      however, the longevity of PSPs in dental practice is not yet established. The aim
      of this study was to determine the service life of PSPs in a clinical setting.
      METHODS: Five unused PSPs were exposed with a conventional X-ray device and
      converted into digital images with Digora Optime (Soredex, Milwaukee, WI). These
      were recorded as the baseline images. Subsequent digital images of the plates
      were obtained after 20, 40, 60, 80, 100, 120, 140, 160, 180 and 200 exposures.
      All radiographic images were subtracted from the first digital image (baseline)
      and the mean grey values (MGVs) of the subtracted images were established using
      software. The data were grouped in 3 classes according to the number of exposures
      (20-80; 100-140; 160-200), and were analysed using variance analysis and chi(2)
      tests. RESULTS: The MGVs of the subtracted images varied between 126.25 and
      127.59, and the difference was not significant among the groups (P = 0.11).
      However, the differences between the MGVs of the plates on each exposure settings
      were significantly different than those of the baseline image (P < 0.05).
      CONCLUSIONS: The findings of this study revealed that even though a slight
      deterioration occurred after the first exposure, each plate can be used up to 200
      times. Further studies are required to reach a more concrete conclusion.

PMID- 19114424
TI  - Complex odontoma associated with dentigerous cyst in maxillary sinus: case report
      and computed tomography features.
AB  - Tumoural and cystic lesions are common findings in the daily practice of dental
      professionals and maxillofacial radiologists. However, simultaneous lesions are
      rare and represent a diagnostic challenge to overcome. Among tumoural
      pathologies, odontomas are the most common odontogenic tumour of the jaws. Cystic
      transformation or development from the tumoural capsule are well recognized in
      situations such as ameloblastomas originated from a dentigerous cyst. Otherwise,
      despite literature reports, dentigerous cysts arising from odontomas are very
      rare and could lead to misdiagnosis. Here, we report a case of a complex odontoma
      associated with a dentigerous cyst in the maxillary sinus, focussing on the
      tomographic features and a differential imaging approach to the diagnosis of
      these lesions.

PMID- 19114425
TI  - Brown tumour of the maxilla and mandible: a rare complication of tertiary
      hyperparathyroidism.
AB  - Hyperparathyroidism is nowadays diagnosed early and asymptomatically with the
      improvements in routine biochemical tests and radiological procedures. The late
      bony complications of the disease have therefore started to decline rapidly.
      Brown tumours are one of the bony complications of hyperparathyroidism. The
      mandible is the predominantly affected site in the maxillofacial area. Maxillary
      involvement is rare. Here, an extremely rare case of a 19-year-old male patient
      with brown tumours in his maxilla and mandible associated with tertiary
      hyperparathyroidism is presented. A thorough diagnostic work-up was carried out
      and treatment options for both hyperparathyroidism and brown tumours were
      discussed. The importance of different radiological evaluation methods and the
      consultation between the oral and maxillofacial surgeons, general practitioner
      dentists, endocrinologists and radiologists are emphasised.

PMID- 19114426
TI  - Soft-tissue osteoma in the pterygomandibular space: report of a rare case.
AB  - Osteoma is a slow-growing, benign and uncommon neoplasm located primarily in the
      region of the maxillofacial skeleton. An extraskeletal soft-tissue osteoma is
      exceedingly rare. Here, we report a case of soft-tissue osteoma occurring in the
      pterygomandibular space in a 66-year-old woman. The patient complained of a hard
      mass superior to the left posterior teeth. Clinical examination did not reveal
      any extraoral swelling, facial asymmetry or difficulty in mouth opening, and the
      regional lymph nodes were non-palpable. CT images revealed well-circumscribed
      dense, radiopaque masses located between the left side of the maxilla and the
      lateral plate of the left pterygoid process and the left ramus of the mandible.
      Intraoperatively, the masses were completely surrounded by soft tissues with no
      attachment to the bone. Histological examination indicated the diagnosis of
      cancellous osteoma.

PMID- 19114427
TI  - Ethical studies, ethical publication.

PMID- 19114428
TI  - How can revalidation help to tackle local concerns about doctors' health?

PMID- 19114429
TI  - Sebastiao Salgado Oil Well Burhan Kuwait (1991).

PMID- 19114431
TI  - Occupational medicine in Iran.

PMID- 19114432
TI  - Use of photography in HAVS.

PMID- 19114433
TI  - Therapeutic aquatic exercise in the treatment of low back pain: a systematic
      review.
AB  - OBJECTIVE: To examine the effectiveness of therapeutic aquatic exercise in the
      treatment of low back pain. DESIGN: A systematic review. METHODS: A search was
      performed of PEDro, CINAHL (ovid), PUBMED, Cochrane Controlled Trials Register
      and SPORTDiscus databases to identify relevant studies published between 1990 and
      2007. POPULATION: Adults suffering from low back pain. INTERVENTION: All types of
      therapeutic aquatic exercise. COMPARISON: All clinical trials using a control
      group. OUTCOMES: Oswestry Disability Index, McGill Pain Questionnaire, subjective
      assessment scale for pain (e.g. visual analogue scale) and number of work days
      lost as a direct result of low back pain. Methodological quality was assessed
      using the PEDro scale and the SIGN 50 assessment forms. RESULTS: Thirty-seven
      trials were found and seven were accepted into the review. Therapeutic aquatic
      exercise appeared to have a beneficial effect, however, no better than other
      interventions. Methodological quality was considered low in all included studies.
      The heterogeneity among studies, in numbers of subjects, symptoms durations,
      interventions and reporting of outcomes, precluded any extensive meta-analysis of
      the results. CONCLUSION: There was sufficient evidence to suggest that
      therapeutic aquatic exercise is potentially beneficial to patients suffering from
      chronic low back pain and pregnancy-related low back pain. There is further need
      for high-quality trials to substantiate the use of therapeutic aquatic exercise
      in a clinical setting.

PMID- 19114434
TI  - Effectiveness of physiotherapy for adults with cerebellar dysfunction: a
      systematic review.
AB  - OBJECTIVE: To systematically review the literature investigating the
      effectiveness of physiotherapy in adults with cerebellar dysfunction and to
      document treatment strategies currently employed in the physiotherapy management
      of this patient population. DATA SOURCES: Eight electronic databases were
      searched to source English-language studies published up to December 2007.
      Secondary searching of reference lists was also undertaken. REVIEW METHODS:
      Studies were included if they used a quantitative research design to investigate
      the effect of physiotherapy on adults with diagnosed cerebellar dysfunction.
      Three reviewers were involved in study selection. Eligible studies were assessed
      for methodological quality. Data pertaining to the participants, interventions
      received, outcomes measured, and the effectiveness of the intervention were
      systematically extracted and synthesised in a narrative format. RESULTS: Nine
      studies were included in the review. The majority of the studies (n = 7) were
      case studies or case series. The median quality score was 8/16 (range 4-10). The
      studies were heterogeneous in terms of patient characteristics, interventions
      received and outcomes measured. All studies reported positive effects of
      physiotherapy over a range of outcomes measured, in particular balance, gait and
      function. CONCLUSION: There is some evidence that supports the effectiveness of
      physiotherapy in adults with cerebellar dysfunction. However, these results need
      to be interpreted with caution due to the low volume, quality and clinical
      applicability of this evidence. There is a need for further high-quality research
      in this area.

PMID- 19114435
TI  - Evidence for the retraining of sensation after stroke: a systematic review.
AB  - OBJECTIVE: Retraining of sensory function following stroke is frequently
      overlooked in rehabilitation protocols despite more than 60% of patients
      presenting with sensory deficits. Methods to train sensory function include both
      passive and active training protocols. Here we examined the volume and quality of
      the evidence available for both passive and active sensory training following
      stroke. In addition, we aimed to quantify the effect of sensory training on
      impairment and function. DATA SOURCES: Databases searched included MEDLINE, AMED,
      CINAHL, Academic search elite, Scopus and the Cochrane library. Unpublished
      articles were identified using a search engine. REVIEW METHODS: Studies utilizing
      passive or active sensory training paradigms post stroke were identified.
      Methodological quality was examined using the National Health and Medical
      Research Council hierarchy of evidence and the McMaster University critical
      appraisal tool. RESULTS: Fourteen studies met the inclusion criteria; 8 examined
      passive and 6 active sensory training. Methodological quality scores ranged from
      11 to 18.5 (maximum 20). Meta-analysis was performed using three studies
      examining hand function, demonstrating a moderate effect in favour of passive
      sensory training. Other studies were unable to be pooled due to heterogeneity of
      measures or insufficient data. CONCLUSION: Meta-analyses and single studies offer
      some support for the effectiveness of passive sensory training in relation to
      sensory impairment and motor function. However, empirical evidence for active
      sensory training is limited. Further high-quality studies with greater
      statistical power and meaningful clinical measures are required in order to
      accurately determine the effectiveness of sensory retraining following stroke.

PMID- 19114436
TI  - Occupational therapy for people with psychotic conditions in community settings:
      a pilot randomized controlled trial.
AB  - OBJECTIVES: To investigate the effectiveness of a long established intervention,
      occupational therapy for people with psychotic conditions, and to inform future
      research designs. DESIGN: A pilot randomized controlled trial. SETTING: Two
      community mental health teams in a UK city. PARTICIPANTS: Forty-four adults with
      schizophrenia or other psychotic conditions, and functional problems.
      INTERVENTIONS: Twelve months of individualized occupational therapy in community
      settings, as an adjunct to usual care and compared to treatment as usual. A two
      to one randomization ratio was used in favour of occupational therapy. OUTCOME
      MEASURES: Social Functioning Scale, Scale for the Assessment of Negative Symptoms
      and employment. RESULTS: Both groups' scores on Social Functioning Scale and
      Scale for the Assessment of Negative Symptoms showed significant improvement over
      12 months. The Social Functioning Scale overall mean difference for occupational
      therapy was 2.33, P=0.020 and for treatment as usual was 6.17, P=0.023. The Scale
      for the Assessment of Negative Symptoms total mean difference for occupational
      therapy was -16.25, P<0.001 and for treatment as usual was -17.36, P= 0.011.
      There were no differences between the two groups on any of the outcome measures.
      After 12 months the occupational therapy group showed clinically significant
      improvements that were not apparent in the control group. These were in four
      subscales of the Social Functioning Scale: relationships, independence
      performance, independence competence and recreation. Out of 30 people receiving
      occupational therapy those with a clinical level of negative symptoms reduced
      from 18 (64%) to 13 (46%), P=0.055. CONCLUSION: This pilot study suggested that
      individualized occupational therapy may contribute to recovery but more focus is
      recommended on people's cognitive abilities and employment.

PMID- 19114437
TI  - Effects of intradialytic exercise training on health-related quality of life
      indices in haemodialysis patients.
AB  - OBJECTIVE: To assess the effects of intradialytic exercise training on health
      related quality of life indices in haemodialysis patients. SUBJECTS/PATIENTS:
      Thirty-five patients on haemodialysis, with a mean (SD) age of 48.8 (13.9) years,
      volunteered to participate in the study. They were randomized either to
      rehabilitation group (group A: 19 patients), following a 10-month intradialytic
      exercise training programme or to control group (group B: 14 patients). After the
      randomization, two of the patients, one of each group, withdrew from the study
      for reasons unrelated to exercise training. METHOD: All patients at the beginning
      and the end of the study underwent clinical examination, laboratory tests and a
      treadmill exercise testing with spiroergometric study for the evaluation of their
      aerobic capacity (Vo(2peak)). A formal psychosocial assessment, which included
      affective (Beck Depression Inventory), health-related quality of life (Quality of
      Life Index, Living Questionnaire of Minnesota, Life Satisfaction Index and Short
      Form-36 questionnaire) and personality (Eysenck Personality Questionnaire)
      parameters, was evaluated at beginning and end of the study. The dose of
      erythropoietin was changed as needed, according to the level of the haemoglobin,
      aiming to keep it at 11 (2) g/dL during the study. RESULTS: Baseline values were
      similar between the two groups. After training in group A, Vo(2peak) was
      increased by 21.1% (P<0.05) and exercise time by 23.6% (P<0.05). Moreover, group
      A showed a decrease in self-reported depression (Beck Depression Index) of 39.4%
      (P<0.001). In addition, trained patients demonstrated a significant improvement
      in Quality of Life Index (from 6.5 (1.8) to 9.0 (1.3), P<0.001) and Life
      Satisfaction Index (from 44.8 (8.6) to 53.0 (5.6), P<0.001), and an increase in
      the Physical Component Scale of the SF-36 (from 40.5 (5.6) to 44.5 (5.5),
      P<0.05), while the Mental Component Scale remained unchanged. Multiple regression
      analysis indicated that the improvement in quality of life depended on the
      participation in exercise programmes, the effects of training and the reduction
      in the level of depression. No changes were observed in Eysenck Personality
      Questionnaire by the end of the study, while all the above parameters remained
      almost unchanged in the controls. CONCLUSION: The results demonstrated that
      intradialytic exercise training improves both physical functioning and
      psychological status in haemodialysis patients, leading to an improvement of
      patients' quality of life.

PMID- 19114438
TI  - Botulinum toxin (Dysport) treatment of the spastic gastrocnemius muscle in
      children with cerebral palsy: a randomized trial comparing two injection volumes.
AB  - OBJECTIVE: To compare the effect of equivalent doses in two different volumes of
      botulinum toxin type A (Dysport) on gastrocnemius spasticity. DESIGN: Single
      blind, randomized, controlled trial. SETTING: Hospital rehabilitation department.
      SUBJECTS: Twenty-two children with spastic diplegic or quadriplegic cerebral
      palsy. INTERVENTION: High (500 U/5 mL) and low (500 U/1 mL)-volume preparations
      of Dysport were injected into the gastrocnemius muscles, each child randomly
      receiving one preparation in the right and the other in the left leg. MAIN
      MEASURES: Dynamic ankle joint range of motion (ROM), passive ROM of the ankle
      joint, modified Ashworth Scale scores, and the areas of the compound muscle
      action potential assessed before treatment and at four and eight weeks post
      treatment. RESULTS: Both legs improved significantly. The mean (SD) improvements
      between baseline and the end of follow-up were 19.7 (10.83) degrees for dynamic
      ROM, 8.4 (9.19) degrees for passive ROM, -1.3 (0.6) for modified Ashworth Scale
      scores, and -9.4 (11.41) mV-ms for compound muscle action potential in the high
      volume group; and 13.5 (10.45) degrees for dynamic ROM, 7.4 (7.88) for passive
      ROM, -0.9 (0.5) for modified Ashworth Scale scores, and -5.9 (7.50) mV-ms for
      areas of compound muscle action potential in the low-volume group. The high
      volume preparation yielded significantly greater improvement in dynamic ROM
      (P<0.001), muscle tone (P < 0.001), and lower compound muscle action potential
      area (P = 0.006). CONCLUSIONS: A high-volume preparation of Dysport is more
      effective than a low volume in reducing spasticity in the gastrocnemius muscle.

PMID- 19114439
TI  - Sense of coherence and mental health rehabilitation.
AB  - OBJECTIVE: To provide an understanding of Antonovsky's sense of coherence theory
      in relation to rehabilitation and to explain how applying his theory in
      rehabilitation practice can be beneficial. The focus of this paper will be on the
      rehabilitation and recovery of those with mental health issues. FINDINGS: Sense
      of coherence theory helps explain the process of recovery for those with mental
      health issues. There is substantial evidence that sense of coherence plays a
      central role in coping with stressors in the rehabilitation/recovery process and
      that it contributes to mental health and psychosocial functioning. If
      rehabilitation services adopt a salutogenic approach and seek to enhance a
      client's sense of coherence then this can be beneficial in terms of the client's
      rehabilitation and recovery. CONCLUSION: Rehabilitation services should ensure
      that they have rehabilitation goals that strengthen individuals' sense of
      coherence. Further investigation is required into the development of
      rehabilitation programmes with sense of coherence theory as part of their
      foundation.

PMID- 19114440
TI  - Training patients in Time Pressure Management, a cognitive strategy for mental
      slowness.
AB  - PURPOSE: To provide clinical practitioners with a framework for teaching patients
      Time Pressure Management, a cognitive strategy that aims to reduce disabilities
      arising from mental slowness due to acquired brain injury. Time Pressure
      Management provides patients with compensatory strategies to deal with time
      pressure in daily life. Application of the training in clinical practice is
      illustrated using two case examples from a randomized controlled trial on the
      effectiveness of Time Pressure Management for patients with stroke. RATIONALE:
      The Time Pressure Management approach is based on Michon's task analysis,
      describing levels of decision-making in complex cognitive tasks. Decisions with
      little or no time pressure are not impaired by mental slowness. Therefore,
      patients should try to transfer actions from situations with high time pressure
      to situations where the preserved decision levels with little or no time pressure
      can work. THEORY INTO PRACTICE: Several factors are required to teach patients to
      use Time Pressure Management. First, sufficient awareness is needed to recognize
      that there is a deficit and behavioural change is necessary. Sufficient awareness
      is also required to recognize and anticipate time pressure situations and to
      realize that the strategy is helpful and might also be useful in new and more
      difficult circumstances. Second, adequate motivation is needed to learn the
      strategy. And finally, the training should be adjusted to the patient's
      individual learning abilities and cognitive skills.

PMID- 19114441
TI  - How many body locations need to be tested when assessing sensation after stroke?
      An investigation of redundancy in the Rivermead Assessment of Somatosensory
      Performance.
AB  - OBJECTIVE: Assessing sensation after stroke is time consuming. This study aimed
      to identify how many body locations need to be tested to establish whether
      sensation is ;intact', ;impaired' or ;absent' and to assess validity of that
      classification. DESIGN: Participants' sensation was tested in a single assessment
      session. Agreement between the scores for individual anatomical sites and those
      for the whole limb was calculated using a weighted kappa and percentage agreement
      for each modality. High agreement between tests indicated redundancy, suggesting
      that the number of anatomical sites tested could be reduced. The Kruskal-Wallis
      test assessed the validity of classification by comparing a range of measures of
      functional ability in people with intact, impaired and absent sensation. SETTING:
      Hospital-based stroke care. SUBJECTS: One hundred and two patients tested 2-4
      weeks after stroke. MAIN MEASURES: Four proprioceptive and tactile modalities
      were measured using the Rivermead Assessment of Somatosensory Performance.
      RESULTS: Agreement between the total limb score and individual anatomical sites
      was substantial to excellent for all modalities and anatomical sites. Agreement
      was greater than 90% when sensation was intact or absent. The comparison between
      patients with intact, impaired and absent sensation showed significant
      differences in functional mobility, independence in the activities of daily
      living, balance and weakness in people with stroke. CONCLUSIONS: Sensory
      impairment can be classified as ;intact', ;impaired' or ;absent'. There is a high
      redundancy between anatomical sites when the patient's sensation is ;intact' or
      ;absent' and not all sites need to be tested. Reducing the number of sites tested
      will improve usability of the Rivermead Assessment of Somatosensory Performance
      in day-to-day clinical practice.

PMID- 19114445
TI  - Acute dyspnoea, dysphagia, and non-specific chest pain in a smoker.

PMID- 19114446
TI  - A case of hepatomegaly.

PMID- 19114449
TI  - Changes to the regulation of drug prices in the UK.

PMID- 19114450
TI  - Students whose behaviour causes concern: Case history.

PMID- 19114451
TI  - Students whose behaviour causes concern: Am I my brother's keeper?

PMID- 19114452
TI  - Students whose behaviour causes concern: The GMC's view.

PMID- 19114453
TI  - Students whose behaviour causes concern: Ethical perspective.

PMID- 19114454
TI  - Students whose behaviour causes concern: Role of universities.

PMID- 19114456
TI  - Innovations in publishing BMJ research.

PMID- 19114458
TI  - Failure to predict hemolysis and hyperbilirubinemia by IgG subclass in blood
      group A or B infants born to group O mothers.
AB  - OBJECTIVE: Direct antibody titer-positive, blood group A or B neonates who are
      born to group O mothers may be at risk for hemolysis and hyperbilirubinemia.
      Immunoglobulin G1 and immunoglobulin G3 subclasses are associated with increased
      hemolysis relative to immunoglobulin G2 and immunoglobulin G4. We investigated
      whether identification of immunoglobulin G subclass 1 or 3 may be predictive of
      hemolysis and hyperbilirubinemia. METHODS: Direct antibody titer-positive, blood
      group A and B neonates born to group O mothers were tested for the presence of
      immunoglobulin G subclasses 1 and 3 in umbilical cord blood by using a
      commercially available gel testing technology. By inference, neonates in whom
      neither immunoglobulin G1 nor immunoglobulin G3 were detected were designated
      immunoglobulin G2 and/or 4. Mandatory plasma total bilirubin was measured at
      discharge, and additional measurements performed as clinically indicated.
      Hyperbilirubinemia was defined as any plasma total bilirubin value >95th
      percentile for hour of life. Blood carboxyhemoglobin and total hemoglobin
      concentrations were also measured on the predischarge sample. Measured
      carboxyhemoglobin, expressed as percentage of total hemoglobin, was corrected for
      ambient carbon monoxide to derive "corrected carboxyhemoglobin," a sensitive
      index of heme catabolism. The corrected carboxyhemoglobin/total hemoglobin ratio
      was calculated to correct for any differences in total hemoglobin mass between
      groups. RESULTS: Eighty-two infants were studied, 18 of whom were designated as
      immunoglobulin G1, 0 as immunoglobulin G3, and 64 as immunoglobulin G2 and/or 4.
      The incidence of plasma total bilirubin >95th percentile was similar between the
      subgroupings. Corrected carboxyhemoglobin values and corrected
      carboxyhemoglobin/total hemoglobin ratio were also similar between the
      subgroupings. CONCLUSIONS: Immunoglobulin G1 was found in 22% of direct antibody
      titer-positive, group A and B neonates who were born to group O mothers, whereas
      immunoglobulin G3 was rare. Hemolysis and hyperbilirubinemia could not be
      predicted by this gel technique that enabled identification of these
      immunoglobulin G subclasses.

PMID- 19114459
TI  - A mutant plasma membrane protein is stabilized upon loss of Yvh1, a novel
      ribosome assembly factor.
AB  - Pma1-10 is a mutant plasma membrane ATPase defective at the restrictive
      temperature in stability at the cell surface. At 37 degrees, Pma1-10 is
      ubiquitinated and internalized from the plasma membrane for degradation in the
      vacuole. YVH1, encoding a tyrosine phosphatase, is a mutant suppressor of pma1
      10; in the absence of Yvh1, Pma1-10 remains stable at the plasma membrane,
      thereby permitting cells to grow. The RING finger domain of Yvh1, but not its
      phosphatase domain, is required for removal of mutant Pma1-10 from the plasma
      membrane. Yvh1 is a novel ribosome assembly factor: in yvh1Delta cells, free 60S
      and 80S ribosomal subunits are decreased, free 40S subunits are increased, and
      half-mer polysomes are accumulated. Pma1-10 is also stabilized by deletion of 60S
      ribosomal proteins Rpl19a and Rpl35a. We propose that changes in ribosome
      biogenesis caused by loss of Yvh1 or specific ribosomal proteins have effects on
      the plasma membrane, perhaps by producing specific translational changes.

PMID- 19114461
TI  - Molecular spectrum of spontaneous de novo mutations in male and female germline
      cells of Drosophila melanogaster.
AB  - We carried out mutation screen experiments to understand the rate and molecular
      nature of spontaneous de novo mutations in Drosophila melanogaster, which are
      crucial for many evolutionary issues, but still poorly understood. We screened
      for eye-color and body-color mutations that occurred in the germline cells of the
      first generation offspring of wild-caught females. The offspring were from
      matings that had occurred in the field and therefore had a genetic composition
      close to that of flies in natural populations. We employed 1554 F(1) individuals
      from 374 wild-caught females for the experiments to avoid biased contributions of
      any particular genotype. From approximately 8.6 million alleles screened, we
      obtained 10 independent mutants: two point mutations (one for each sex), a single
      deletion of approximately 6 kb in a male, a single transposable element insertion
      in a female, five large deletions ranging in size from 40 to 500 kb in females,
      and a single mutation of unknown nature in a male. The five large deletions were
      presumably generated by nonallelic homologous recombination (NAHR) between
      transposable elements at different locations, illustrating the mutagenic nature
      of recombination. The high occurrence of NAHR that we observed has important
      consequences for genome evolution through the production of segmental
      duplications.

PMID- 19114460
TI  - Isolation and characterization of cul1-7, a recessive allele of CULLIN1 that
      disrupts SCF function at the C terminus of CUL1 in Arabidopsis thaliana.
AB  - Many aspects of plant biology depend on the ubiquitin proteasome system for
      degradation of regulatory proteins. Ubiquitin E3 ligases confer substrate
      specificity in this pathway, and SCF-type ligases comprise a major class of E3s.
      SCF ligases have four subunits: SKP1, CUL1, RBX1, and an F-box protein for
      substrate recognition. The Aux/IAAs are a well-characterized family of SCF
      substrates in plants. Here, we report characterization of a mutant isolated from
      a genetic screen in Arabidopsis thaliana designed to identify plants defective in
      degradation of an Aux/IAA fusion protein, Aux/IAA1-luciferase (IAA1-LUC). This
      mutant exhibited fourfold slower IAA1-LUC degradation compared with the
      progenitor line, and seedlings displayed altered auxin responses. Experiments
      identified the mutant as an allele of CUL1, named cul1-7. The cul1-7 mutation
      affects the C terminus of the protein, results in reduced cul1-7 levels, and
      interferes with RBX1 interaction. cul1-7 seedlings are defective in degradation
      of an endogenous SCF substrate, Repressor of ga1-3 (RGA), and have altered
      responses to gibberellins. cul1-7 seedlings exhibit slower degradation of the
      light-labile red/far-red photoreceptor phytochrome A and are photomorphogenic in
      the dark. This mutation represents the first reported allele of CUL1 to directly
      affect subunit interactions at the CUL1 C terminus.

PMID- 19114462
TI  - Identification of a cranberry juice product that inhibits enteric CYP3A-mediated
      first-pass metabolism in humans.
AB  - An in vivo study in rats showed a cranberry juice product to inhibit the
      intestinal first-pass metabolism of the CYP3A substrate nifedipine. However, a
      clinical study involving the CYP3A probe substrate midazolam and a different
      cranberry juice product showed no interaction. Because the composition of
      bioactive components in natural products can vary substantially, a systematic in
      vitro-in vivo approach was taken to identify a cranberry juice capable of
      inhibiting enteric CYP3A in humans. First, the effects of five cranberry juices,
      coded A through E, were evaluated on midazolam 1'-hydroxylation activity in human
      intestinal microsomes. Juice E was the most potent, ablating activity at 0.5%
      juice (v/v) relative to control. Second, juice E was fractionated to generate
      hexane-, chloroform-, butanol-, and aqueous-soluble fractions. The hexane- and
      chloroform-soluble fractions at 50 microg/ml were the most potent, inhibiting by
      77 and 63%, respectively, suggesting that the CYP3A inhibitors reside largely in
      these more lipophilic fractions. Finally, juice E was evaluated on the oral
      pharmacokinetics of midazolam in 16 healthy volunteers. Relative to water, juice
      E significantly increased the geometric mean area under the curve (AUC)(0
      infinity) of midazolam by approximately 30% (p=0.001), decreased the geometric
      mean 1'-hydroxymidazolam/midazolam AUC(0-infinity) ratio by approximately 40%
      (p<0.001), and had no effect on geometric mean terminal half-life, indicating
      inhibition of enteric, but not hepatic, CYP3A-mediated first-pass metabolism of
      midazolam. This approach both showed a potential drug interaction liability with
      cranberry juice and substantiated that rigorous in vitro characterization of
      dietary substances is required before initiation of clinical drug-diet
      interaction studies.

PMID- 19114463
TI  - Fexofenadine brain exposure and the influence of blood-brain barrier P
      glycoprotein after fexofenadine and terfenadine administration.
AB  - P-glycoprotein (P-gp) plays an important role in determining net brain uptake of
      fexofenadine. Initial in vivo experiments with 24-h subcutaneous osmotic minipump
      administration demonstrated that fexofenadine brain penetration was 48-fold
      higher in mdr1a(-/-) mice than in mdr1a(+/+) mice. In contrast, the P-gp efflux
      ratio at the blood-brain barrier (BBB) for fexofenadine was only approximately 4
      using an in situ brain perfusion technique. Pharmacokinetic modeling based on the
      experimental results indicated that the apparent fexofenadine P-gp efflux ratio
      is time-dependent due to low passive permeability at the BBB. Fexofenadine brain
      penetration after terfenadine administration was approximately 25- to 27-fold
      higher than after fexofenadine administration in both mdr1a(+/+) and mdr1a(-/-)
      mice, consistent with terfenadine metabolism to fexofenadine in murine brain
      tissue. The fexofenadine formation rate after terfenadine in situ brain perfusion
      was comparable with that in a 2-h brain tissue homogenate in vitro incubation.
      The fexofenadine formation rate increased approximately 5-fold during a 2-h brain
      tissue homogenate incubation with hydroxyl-terfenadine, suggesting that the
      hydroxylation of terfenadine is the rate-limiting step in fexofenadine formation.
      Moreover, regional brain metabolism seems to be an important factor in
      terfenadine brain disposition and, consequently, fexofenadine brain exposure.
      Taken together, these results indicate that the fexofenadine BBB P-gp efflux
      ratio has been underestimated previously due to the lack of complete
      equilibration of fexofenadine across the blood-brain interface under typical
      experimental paradigms.

PMID- 19114464
TI  - Our young student scientists: implications for school nurses.

PMID- 19114465
TI  - Male adolescent bullying and the school shooter.
AB  - An extensive review of the literature reveals that adolescent male victims of
      peer bullying suffer somatic and emotional consequences from being victimized.
      Limited research on school shooters found that a significant number of them were
      adolescents who were targets of bullies and claimed their shootings were in
      response to their victimization. To date, there is no profile of the school
      shooter, although research has suggested various dynamics that contribute to an
      environment that can predispose a community to a school shooting. No published
      nursing research has examined the relationship between bullying and the school
      shooter or that of adolescents who experience peer bullying. Despite findings
      from other disciplines, such as law enforcement, education, sociology, and
      psychology, school nurses need to be part of the team to recognize the bullied
      teen and intervene before there are serious life-threatening consequences.

PMID- 19114466
TI  - Clinical education partnership: a model for school district and college of
      nursing collaboration.
AB  - Collaboration between school districts and universities has potential to increase
      the level of health services available in schools while providing quality public
      health clinical nursing placements for universities. This article describes the
      development, implementation, and evaluation of the Clinical Education Partnership
      Model (CEPM), a dynamic framework that specifies four sets of factors necessary
      for high-quality clinical learning experiences for nursing students in school
      settings: essential school district structures, essential college of nursing
      curriculum and arrangements, the interface of the district and university within
      the community context, and program outcomes. The CEPM was piloted over three
      semesters with public health nursing students with positive evaluative feedback
      and shows evidence of sustainability. The CEPM provides a solid foundation for
      ongoing mutually beneficial collaborative relationships in which school nursing
      practice and school health are enhanced and academic programs are enriched.

PMID- 19114467
TI  - Preventing community-associated methicillin-resistant Staphylococcus aureus among
      student athletes.
AB  - Methicillin-resistant Staphylococcus aureus (MRSA) was once thought to be a
      bacterium causing infections in only hospitalized patients. However, a new strain
      of MRSA has emerged among healthy individuals who have not had any recent
      exposure to a hospital or to medical procedures. This new strain is known as
      community-associated MRSA. Studies have shown the rates of MRSA infection are
      increasing throughout the United States and that some populations are at greater
      risk of acquiring these infections. One population at greater risk is athletes.
      Educating student athletes, parents, coaches, and administrators about the
      seriousness of this infection and how to prevent and manage it in the school
      setting is an important role of the school nurse. The goal of this education is
      to prevent the spread of MRSA organisms, thereby reducing student absenteeism and
      the related costs of treating MRSA infections.

PMID- 19114468
TI  - Examining attendance, academic performance, and behavior in obese adolescents.
AB  - Although academics and safety continue to rank as high-priority issues in public
      schools, educators and administrators are beginning to recognize the importance
      of student health on school success. This move toward a holistic approach
      suggests that efforts to improve a student's physical, social, and emotional well
      being are as important as efforts to increase test scores. Adolescent obesity is
      epidemic, and it is a complex integration of social, psychological, and physical
      factors that exacerbate the turbulent transitional years of adolescence.
      Adolescents are vulnerable to issues related to weight, and they are at risk for
      suffering obesity's negative effects, thereby resulting in unfortunate school
      outcomes such as decreased rates of attendance, poor academic performance, and
      school suspensions. Disparities related to overweight and obesity exist;
      therefore, the negative effects of obesity may disproportionately affect
      minorities and poor schoolchildren. Examining school outcomes for the overweight
      or obese adolescent is crucial and may provide valuable insight into constructive
      changes required for a responsive school environment.

PMID- 19114469
TI  - Lessons learned from an elementary school norovirus outbreak.
AB  - Outbreaks of norovirus have been on the increase. The virus often spreads quickly
      through schools and similar institutions. The school nurse may be able to
      minimize the impact of a school norovirus outbreak by providing accurate
      information about the disease, the scope of the local situation, and instruction
      on infection control measures. This article describes a norovirus outbreak
      experienced by an elementary school in which 41% of students were afflicted. The
      experience of the school nurse managing the outbreak is examined, and
      recommendations are offered for use by other school nurses facing similar
      outbreaks to reduce the spread and impact of the virus. Often the very measures
      that school personnel instinctively employ, such as the increased use of hand
      sanitizers and systematic use of disinfecting agents that are actually
      ineffective against norovirus, can have the opposite of the intended effect and
      inadvertently further the spread of the disease.

PMID- 19114470
TI  - Bell's palsy in children: role of the school nurse in early recognition and
      referral.
AB  - Bell's palsy is the most common condition affecting facial nerves. It is an
      acute, rapidly progressing, idiopathic, unilateral facial paralysis that is
      generally self-limiting and non-life threatening that occurs in all age groups
      (Okuwobi, Omole, & Griffith, 2003). The school nurse may be the first person to
      assess facial palsy and muscle weakness in children. Because facial palsy and
      muscle weakness may be an indicator of a serious or life threatening condition,
      the school nurse plays a critical role in early recognition and referral. The
      Gordon Facial Muscle Weakness Assessment Form is presented as a tool designed to
      assist school nurses in recognizing children with facial muscle weakness and in
      determining whether a primary health care provider referral should be considered
      immediate or urgent.

PMID- 19114471
TI  - Parental perceptions of childhood overweight in the Mexican American population:
      an integrative review.
AB  - The prevalence of overweight in Mexican American children has been increasing at
      a steady rate over the past few years. People of Mexican origin make up the
      largest proportion of the Hispanic population, which has been reported by the
      U.S. Census Bureau to be the fastest growing ethnic group in the United States.
      The purpose of this integrative review was to examine and summarize the current
      research on parental perceptions of childhood overweight in the Mexican American
      population. Four main themes evolved as a result of the data analysis: parental
      perception of overweight, parental practices, household food security status, and
      acculturation. School nurses are in a position to influence children in improving
      their nutritional status and increasing their physical activity. Understanding
      cultural values and beliefs regarding health status and overweight of Mexican
      American families should be a priority for school nurses. Identifying food
      related parenting styles and the concept of acculturation should also be
      considered prior to incorporating relevant interventions in the school setting.

PMID- 19114472
TI  - A comparison of the number of hours of sleep in high school students who took
      advanced placement and/or college courses and those who did not.
AB  - This study investigated the association between sleep deprivation and enrollment
      in Advanced Placement (AP) and/or college courses among high school students.
      Approximately 4,000 surveys were distributed, and 2,197 completed surveys were
      returned from students in Grades 9 to 12 at 15 high schools in Iowa. Findings
      indicated the majority of high school students were sleep deprived. Sleep
      deprivation was significantly associated with enrollment in AP/college courses.
      Results indicated that enrollment in AP/college courses had a greater impact on
      younger students than older students. Compared with non-AP/college course takers,
      AP/college course takers slept approximately 20 minutes less per night.
      Specifically, 9th- and 10th-grade AP/college course takers slept approximately 1
      hour less and 40 minutes less, respectively. In addition, students enrolled in
      two or more AP/college classes received 1 hour less and 30 minutes less among
      10th and 11th graders, respectively. These results provide useful information on
      adolescent sleep patterns for school nurses.

PMID- 19114474
TI  - Regulation of cyclic lipopeptide biosynthesis in Pseudomonas fluorescens by the
      ClpP protease.
AB  - Cyclic lipopeptides produced by Pseudomonas species exhibit potent surfactant and
      broad-spectrum antibiotic properties. Their biosynthesis is governed by large
      multimodular nonribosomal peptide synthetases, but little is known about the
      genetic regulatory network. This study provides, for the first time, evidence
      that the serine protease ClpP regulates the biosynthesis of massetolides, cyclic
      lipopeptides involved in swarming motility, biofilm formation, and antimicrobial
      activity of Pseudomonas fluorescens SS101. The results show that ClpP affects the
      expression of luxR(mA), the transcriptional regulator of the massetolide
      biosynthesis genes massABC, thereby regulating biofilm formation and swarming
      motility of P. fluorescens SS101. Transcription of luxR(mA) was significantly
      repressed in the clpP mutant, and introduction of luxR(mA) restored, in part,
      massetolide biosynthesis and swarming motility of the clpP mutant. Site-directed
      mutagenesis and expression analyses indicated that the chaperone subunit ClpX and
      the Lon protease are not involved in regulation of massetolide biosynthesis and
      are transcribed independently of clpP. Addition of Casamino Acids enhanced the
      transcription of luxR(mA) and massABC in the clpP mutant, leading to a partial
      rescue of massetolide production and swarming motility. The results further
      suggested that, at the transcriptional level, ClpP-mediated regulation of
      massetolide biosynthesis operates independently of regulation by the GacA/GacS
      two-component system. The role of amino acid metabolism and the putative
      mechanisms underlying ClpP-mediated regulation of cyclic lipopeptide
      biosynthesis, swarming motility, and growth in P. fluorescens are discussed.

PMID- 19114475
TI  - Ferredoxin-NADP+ reductase from Pseudomonas putida functions as a ferric
      reductase.
AB  - Pseudomonas putida harbors two ferredoxin-NADP(+) reductases (Fprs) on its
      chromosome, and their functions remain largely unknown. Ferric reductase is
      structurally contained within the Fpr superfamily. Interestingly, ferric
      reductase is not annotated on the chromosome of P. putida. In an effort to
      elucidate the function of the Fpr as a ferric reductase, we used a variety of
      biochemical and physiological methods using the wild-type and mutant strains. In
      both the ferric reductase and flavin reductase assays, FprA and FprB
      preferentially used NADPH and NADH as electron donors, respectively. Two Fprs
      prefer a native ferric chelator to a synthetic ferric chelator and utilize free
      flavin mononucleotide (FMN) as an electron carrier. FprB has a higher k(cat)/K(m)
      value for reducing the ferric complex with free FMN. The growth rate of the fprB
      mutant was reduced more profoundly than that of the fprA mutant, the growth rate
      of which is also lower than the wild type in ferric iron-containing minimal
      media. Flavin reductase activity was diminished completely when the cell extracts
      of the fprB mutant plus NADH were utilized, but not the fprA mutant with NADPH.
      This indicates that other NADPH-dependent flavin reductases may exist.
      Interestingly, the structure of the NAD(P) region of FprB, but not of FprA,
      resembled the ferric reductase (Fre) of Escherichia coli in the homology
      modeling. This study demonstrates, for the first time, the functions of Fprs in
      P. putida as flavin and ferric reductases. Furthermore, our results indicated
      that FprB may perform a crucial role as a NADH-dependent ferric/flavin reductase
      under iron stress conditions.

PMID- 19114476
TI  - The CiaR response regulator in group B Streptococcus promotes intracellular
      survival and resistance to innate immune defenses.
AB  - Group B Streptococcus (GBS) is major cause of invasive disease in newborn infants
      and the leading cause of neonatal meningitis. To gain access to the central
      nervous system (CNS), GBS must not only subvert host defenses in the bloodstream
      but also invade and survive within brain microvascular endothelial cells (BMEC),
      the principal cell layer composing the blood-brain barrier (BBB). While several
      GBS determinants that contribute to the invasion of BMEC have been identified,
      little is known about the GBS factors that are required for intracellular
      survival and ultimate disease progression. In this study we sought to identify
      these factors by screening a random GBS mutant library in an in vitro survival
      assay. One mutant was identified which contained a disruption in a two-component
      regulatory system homologous to CiaR/CiaH, which is present in other
      streptococcal pathogens. Deletion of the putative response regulator, ciaR, in
      GBS resulted in a significant decrease in intracellular survival within
      neutrophils, murine macrophages, and human BMEC, which was linked to increased
      susceptibility to killing by antimicrobial peptides, lysozyme, and reactive
      oxygen species. Furthermore, competition experiments with mice showed that wild
      type GBS had a significant survival advantage over the GBS DeltaciaR mutant in
      the bloodstream and brain. Microarray analysis comparing gene expression between
      wild-type and DeltaciaR mutant GBS bacteria revealed several CiaR-regulated genes
      that may contribute to stress tolerance and the subversion of host defenses by
      GBS. Our results identify the GBS CiaR response regulator as a crucial factor in
      GBS intracellular survival and invasive disease pathogenesis.

PMID- 19114478
TI  - Regulation of expression of the region 3 promoter of the Escherichia coli K5
      capsule gene cluster involves H-NS, SlyA, and a large 5' untranslated region.
AB  - Escherichia coli group 2 capsule gene clusters are temperature regulated, being
      expressed at 37 degrees C but not at 20 degrees C. Expression is regulated at the
      level of transcription by two convergent promoters, PR1 and PR3. In this paper,
      we show that regulation of transcription from PR3 involves a number of novel
      features including H-NS, SlyA, and a large 741-bp 5' untranslated region (UTR). H
      NS represses transcription from PR3 at 20 degrees C and binds both 5' and 3' of
      the transcription start site. The 3' downstream regulatory element (DRE) was
      essential for temperature-dependent H-NS repression. At 37 degrees C, SlyA
      activates transcription independent of H-NS but maximal transcription requires H
      NS. The UTR is present between the transcription start site and the first gene in
      the operon, kpsM. We demonstrate that the UTR, as well as containing the H-NS
      DRE, functions to moderate the extent of transcription that reaches kpsM and
      allows the binding of antitermination factor RfaH.

PMID- 19114477
TI  - Characterization of the Escherichia coli O157:H7 Sakai GadE regulon.
AB  - Integrating laterally acquired virulence genes into the backbone regulatory
      network is important for the pathogenesis of Escherichia coli O157:H7, which has
      captured many virulence genes through horizontal transfer during evolution. GadE
      is an essential transcriptional activator of the glutamate decarboxylase (GAD)
      system, the most efficient acid resistance (AR) mechanism in E. coli. The full
      contribution of GadE to the AR and virulence of E. coli O157:H7 remains largely
      unknown. We inactivated gadE in E. coli O157:H7 Sakai and compared global
      transcription profiles of the mutant with that of the wild type in the
      exponential and stationary phases of growth. Inactivation of gadE significantly
      altered the expression of 60 genes independently of the growth phase and of 122
      genes in a growth phase-dependent manner. Inactivation of gadE markedly
      downregulated the expression of gadA, gadB, and gadC and of many acid fitness
      island genes. Nineteen genes encoded on the locus of enterocyte effacement (LEE),
      including ler, showed a significant increase in expression upon gadE
      inactivation. Inactivation of ler in the DeltagadE strain reversed the effect of
      gadE deletion on LEE expression, indicating that Ler is necessary for LEE
      repression by GadE. GadE is also involved in downregulation of LEE expression
      under conditions of moderately acidic pH. Characterization of AR of the DeltagadE
      strain revealed that GadE is indispensable for a functional GAD system and for
      survival of E. coli O157:H7 in a simulated gastric environment. Altogether, these
      data indicate that GadE is critical for the AR of E. coli O157:H7 and that it
      plays an important role in virulence by downregulating expression of LEE.

PMID- 19114479
TI  - Surface translocation by Legionella pneumophila: a form of sliding motility that
      is dependent upon type II protein secretion.
AB  - Legionella pneumophila exhibits surface translocation when it is grown on a
      buffered charcoal yeast extract (BCYE) containing 0.5 to 1.0% agar. After 7 to 22
      days of incubation, spreading legionellae appear in an amorphous, lobed pattern
      that is most manifest at 25 to 30 degrees C. All nine L. pneumophila strains
      examined displayed the phenotype. Surface translocation was also exhibited by
      some, but not all, other Legionella species examined. L. pneumophila mutants that
      were lacking flagella and/or type IV pili behaved as the wild type did when
      plated on low-percentage agar, indicating that the surface translocation is not
      swarming or twitching motility. A translucent film was visible atop the BCYE
      agar, advancing ahead of the spreading legionellae. Based on its abilities to
      disperse water droplets and to promote the spreading of heterologous bacteria,
      the film appeared to manipulate surface tension and, as such, acted like a
      surfactant. Indeed, a sample obtained from the film rapidly dispersed when it was
      spotted onto a plastic surface. L. pneumophila type II secretion (Lsp) mutants,
      but not their complemented derivatives, were defective for both surface
      translocation and film production. In contrast, mutants defective for type IV
      secretion exhibited normal surface translocation. When lsp mutants were spotted
      onto film produced by the wild type, they were able to spread, suggesting that
      type II secretion promotes the elaboration of the Legionella surfactant.
      Together, these data indicate that L. pneumophila exhibits a form of surface
      translocation that is most akin to "sliding motility" and uniquely dependent upon
      type II secretion.

PMID- 19114480
TI  - Complete genome sequence of the anaerobic, protein-degrading hyperthermophilic
      crenarchaeon Desulfurococcus kamchatkensis.
AB  - Desulfurococcus kamchatkensis is an anaerobic organotrophic hyperthermophilic
      crenarchaeon isolated from a terrestrial hot spring. Its genome consists of a
      single circular chromosome of 1,365,223 bp with no extrachromosomal elements. A
      total of 1,474 protein-encoding genes were annotated, among which 205 are
      exclusive for D. kamchatkensis. The search for a replication origin site revealed
      a single region coinciding with a global extreme of the nucleotide composition
      disparity curve and containing a set of crenarchaeon-type origin recognition
      boxes. Unlike in most archaea, two genes encoding homologs of the eukaryotic
      initiator proteins Orc1 and Cdc6 are located distantly from this site. A number
      of mobile elements are present in the genome, including seven transposons
      representing IS607 and IS200/IS605 families and multiple copies of miniature
      inverted repeat transposable elements. Two large clusters of regularly
      interspaced repeats are present; none of the spacer sequences matches known
      archaeal extrachromosomal elements, except one spacer matches the sequence of a
      resident gene of D. kamchatkensis. Many of the predicted metabolic enzymes are
      associated with the fermentation of peptides and sugars, including more than 30
      peptidases with diverse specificities, a number of polysaccharide degradation
      enzymes, and many transporters. Consistently, the genome encodes both enzymes of
      the modified Embden-Meyerhof pathway of glucose oxidation and a set of enzymes
      needed for gluconeogenesis. The genome structure and content reflect the
      organism's nutritionally diverse, competitive natural environment, which is
      periodically invaded by viruses and other mobile elements.

PMID- 19114481
TI  - Streptococcus agalactiae CspA is a serine protease that inactivates chemokines.
AB  - Streptococcus agalactiae (group B Streptococcus [GBS]) remains a leading cause of
      invasive infections in neonates and has emerged as a pathogen of the
      immunocompromised and elderly populations. The virulence mechanisms of GBS are
      relatively understudied and are still poorly understood. Previous evidence
      indicated that the GBS cspA gene is necessary for full virulence and the cleavage
      of fibrinogen. The predicted cspA product displays homology to members of the
      extracellular cell envelope protease family. CXC chemokines, many of which can
      recruit neutrophils to sites of infection, are important signaling peptides of
      the immune system. In this study, we purified CspA and demonstrated that it
      readily cleaved the CXC chemokines GRO-alpha, GRO-beta, GRO-gamma, neutrophil
      activating peptide 2 (NAP-2), and granulocyte chemotactic protein 2 (GCP-2) but
      did not cleave interleukin-8. CspA did not cleave a panel of other test
      substrates, suggesting that it possesses a certain degree of specificity. CXC
      chemokines also underwent cleavage by whole GBS cells in a cspA-dependent manner.
      CspA abolished the abilities of three representative CXC chemokines, GRO-gamma,
      NAP-2, and GCP-2, to attract and activate neutrophils. Genetic and biochemical
      evidence indicated that CspA is a serine protease with S575 at its active site.
      D180 was also implicated as part of the signature serine protease catalytic
      triad, and both S575 and D180 were required for both N-terminal and C-terminal
      autocatalytic processing of CspA.

PMID- 19114482
TI  - Social interactions and distribution of Bacillus subtilis pherotypes at
      microscale.
AB  - Bacillus subtilis strains communicate through the comQXPA quorum sensing (QS)
      system, which regulates genes expressed during early stationary phase. A high
      polymorphism of comQXP' loci was found in closely related strains isolated from
      desert soil samples separated by distances ranging from meters to kilometers. The
      observed polymorphism comprised four communication groups (pherotypes), such that
      strains belonging to the same pherotype exchanged information efficiently but
      strains from different pherotypes failed to communicate. To determine whether the
      same level of polymorphism in the comQXP' QS system could be detected at
      microscale, B. subtilis isolates were obtained from two separate 1-cm(3) soil
      samples, which were progressively divided into smaller sections. Cross-activation
      studies using pherotype-responsive reporter strains indicated the same number of
      communication pherotypes at microscale as previously determined at macroscale.
      Sequencing of the housekeeping gene gyrA and the QS comQ gene confirmed different
      evolutionary rates of these genes. Furthermore, an asymmetric communication
      response was detected inside the two pherotype clusters, suggesting continuous
      evolution of the QS system and possible development of new languages. To our
      knowledge, this is the first microscale study demonstrating the presence of
      different QS languages among isolates of one species, and the implications of
      this microscale diversity for microbial interactions are discussed.

PMID- 19114483
TI  - Essential role of the SycP chaperone in type III secretion of the YspP effector.
AB  - The Ysa type III secretion (T3S) system enhances gastrointestinal infection by
      Yersinia enterocolitica bv. 1B. One effector protein targeted into host cells is
      YspP, a protein tyrosine phosphatase. It was determined in this study that the
      secretion of YspP requires a chaperone, SycP. Genetic analysis showed that
      deletion of sycP completely abolished the secretion of YspP without affecting the
      secretion of other Ysps by the Ysa T3S system. Analysis of the secretion and
      translocation signals of YspP defined the first 73 amino acids to form the
      minimal region of YspP necessary to promote secretion and translocation by the
      Ysa T3S system. Function of the YspP secretion/translocation signals was
      dependent on SycP. Curiously, when YspP was constitutively expressed in Y.
      enterocolitica bv. 1B, it was recognized and secreted by the Ysc T3S system and
      the flagellar T3S system. In these cases, the first 21 amino acids were
      sufficient to promote secretion, and while SycP did enhance secretion, it was not
      essential. However, neither the Ysc T3S system nor the flagellar T3S system
      translocated YspP into mammalian cells. This supports a model where SycP confers
      secretion/translocation specificities for YspP by the Ysa T3S system. A series of
      biochemical approaches further established that SycP specifically interacts with
      YspP and protected YspP degradation in the cell prior to secretion. Collectively,
      the evidence suggests that YspP secretion by the Ysa T3S system is a
      posttranslational event.

PMID- 19114484
TI  - Three Mycobacterium tuberculosis Rel toxin-antitoxin modules inhibit
      mycobacterial growth and are expressed in infected human macrophages.
AB  - Mycobacterium tuberculosis protein pairs Rv1246c-Rv1247c, Rv2865-Rv2866, and
      Rv3357-Rv3358, here named RelBE, RelFG, and RelJK, respectively, were identified
      based on homology to the Escherichia coli RelBE toxin:antitoxin (TA) module. In
      this study, we have characterized each Rel protein pair and have established that
      they are functional TA modules. Overexpression of individual M. tuberculosis rel
      toxin genes relE, relG, and relK induced growth arrest in Mycobacterium
      smegmatis; a phenotype that was completely reversible by expression of their
      cognate antitoxin genes, relB, relF, and relJ, respectively. We also provide
      evidence that RelB and RelE interact directly, both in vitro and in vivo.
      Analysis of the genetic organization and regulation established that relBE,
      relFG, and relJK form bicistronic operons that are cotranscribed and
      autoregulated, in a manner unlike typical TA modules. RelB and RelF act as
      transcriptional activators, inducing expression of their respective promoters.
      However, RelBE, RelFG, and RelJK (together) repress expression to basal levels of
      activity, while RelJ represses promoter activity altogether. Finally, we have
      determined that all six rel genes are expressed in broth-grown M. tuberculosis,
      whereas relE, relF, and relK are expressed during infection of human macrophages.
      This is the first demonstration of M. tuberculosis expressing TA modules in broth
      culture and during infection of human macrophages.

PMID- 19114485
TI  - TtgV represses two different promoters by recognizing different sequences.
AB  - Expression of the multidrug efflux pump ttgDEF and ttgGHI operons is modulated in
      vivo mainly by the TtgV repressor. TtgV is a multidrug recognition repressor that
      exhibits a DNA binding domain with a long interaction helix comprising residues
      47 to 64. The pattern of expression of the two pumps is different in Pseudomonas
      putida: in the absence of effectors, the promoter for the ttgD gene is silent,
      whereas the ttgG gene is expressed at a high basal level. This correlates with
      the fact that TtgV exhibits a higher affinity for the ttgD operator (K(D)=10+/-1
      nM) than for the ttgG (K(D)=19+/-1 nM) operator. Sequence analysis revealed that
      both operators are 40% identical, and mutational analysis of the ttgD and ttgG
      operators combined with electrophoretic mobility shift assays and in vivo
      expression analysis suggests that TtgV recognizes an inverted repeat with a high
      degree of palindromicity around the central axis. We generated a collection of
      alanine substitution mutants with substitutions between residues 47 and 64 of
      TtgV. The results of extensive combinations of promoter variants with these TtgV
      alanine substitution mutants revealed that TtgV modulates expression from ttgD
      and ttgG promoters through the recognition of both common and different sequences
      in the two promoters. In this regard, we found that TtgV mutants at residues 48,
      50, 53, 54, 60, and 61 failed to bind ttgG but recognized the ttgD operator. TtgV
      residues R47, R52, L57, and T49 are critical for binding to both operators. Based
      on three-dimensional models, we propose that these residues contact nucleotides
      within the major groove of DNA.

PMID- 19114486
TI  - Genome sequence of the Wolbachia endosymbiont of Culex quinquefasciatus JHB.
AB  - Wolbachia species are endosymbionts of a wide range of invertebrates, including
      mosquitoes, fruit flies, and nematodes. The wPip strains can cause cytoplasmic
      incompatibility in some strains of the Culex mosquito. Here we describe the
      genome sequence of a Wolbachia strain that was discovered in the whole-genome
      sequencing data for the mosquito Culex quinquefasciatus strain JHB.

PMID- 19114487
TI  - Archaeal ApbC/Nbp35 homologs function as iron-sulfur cluster carrier proteins.
AB  - Iron-sulfur clusters may have been the earliest catalytic cofactors on earth, and
      most modern organisms use them extensively. Although members of the Archaea
      produce numerous iron-sulfur proteins, the major cluster assembly proteins found
      in the Bacteria and Eukarya are not universally conserved in archaea. Free-living
      archaea do have homologs of the bacterial apbC and eukaryotic NBP35 genes that
      encode iron-sulfur cluster carrier proteins. This study exploits the genetic
      system of Salmonella enterica to examine the in vivo functionality of apbC/NBP35
      homologs from three archaea: Methanococcus maripaludis, Methanocaldococcus
      jannaschii, and Sulfolobus solfataricus. All three archaeal homologs could
      correct the tricarballylate growth defect of an S. enterica apbC mutant.
      Additional genetic studies showed that the conserved Walker box serine and the
      Cys-X-X-Cys motif of the M. maripaludis MMP0704 protein were both required for
      function in vivo but that the amino-terminal ferredoxin domain was not. MMP0704
      protein and an MMP0704 variant protein missing the N-terminal ferredoxin domain
      were purified, and the Fe-S clusters were chemically reconstituted. Both proteins
      bound equimolar concentrations of Fe and S and had UV-visible spectra similar to
      those of known [4Fe-4S] cluster-containing proteins. This family of dimeric iron
      sulfur carrier proteins evolved before the archaeal and eukaryal lineages
      diverged, representing an ancient mode of cluster assembly.

PMID- 19114488
TI  - Positive control of ferric siderophore receptor gene expression by the Irr
      protein in Bradyrhizobium japonicum.
AB  - Ferric siderophore receptors are components of high-affinity iron-chelate
      transport systems in gram-negative bacteria. The genes encoding these receptors
      are generally regulated by repression. Here, we show that the ferrichrome
      receptor gene bll4920 and four additional putative ferric siderophore receptor
      genes in Bradyrhizobium japonicum are positively controlled by the regulatory
      protein Irr, as observed by the low level of mRNA transcripts in an irr mutant in
      iron-limited cells. Potential Irr binding sites with iron control element (ICE)
      like motifs were found upstream and distal to the transcription start sites of
      the five receptor genes. However, purified recombinant Irr bound only some of
      those elements. Nevertheless, dissection of the bll4920 promoter region showed
      that a component in extracts of wild-type cells grown in iron-limited media bound
      only in the ICE motif region of the promoter. This binding was not observed with
      extracts of cells from the parent strain grown under high-iron conditions or from
      an irr mutant strain. Furthermore, gel mobility supershift experiments identified
      Irr as the binding protein in cell extracts. Chromatin immunoprecipitation
      experiments demonstrated that Irr occupies the promoters of the five ferric iron
      transport genes in vivo. We conclude that Irr is a direct positive regulator of
      ferric iron transport in B. japonicum.

PMID- 19114489
TI  - Functional characterization of the type III secretion ATPase HrcN from the plant
      pathogen Xanthomonas campestris pv. vesicatoria.
AB  - Many gram-negative plant and animal pathogenic bacteria employ a type III
      secretion (T3S) system to inject effector proteins into the cytosol of eukaryotic
      host cells. The membrane-spanning T3S apparatus is associated with an ATPase that
      presumably provides the energy for the secretion process. Here, we describe the
      role of the predicted ATPase HrcN from the plant pathogenic bacterium Xanthomonas
      campestris pathovar vesicatoria. We show that HrcN hydrolyzes ATP in vitro and is
      essential for T3S and bacterial pathogenicity. Stability of HrcN in X. campestris
      pv. vesicatoria depends on the conserved HrcL protein, which interacts with HrcN
      in vitro and in vivo. Both HrcN and HrcL bind to the inner membrane protein HrcU
      and specifically localize to the bacterial membranes under T3S-permissive
      conditions. Protein-protein interaction studies revealed that HrcN also interacts
      with the T3S substrate specificity switch protein HpaC and the global T3S
      chaperone HpaB, which promotes secretion of multiple effector proteins. Using an
      in vitro chaperone release assay, we demonstrate that HrcN dissociates a complex
      between HpaB and the effector protein XopF1 in an ATP-dependent manner,
      suggesting that HrcN is involved in the release of HpaB-bound effectors. Effector
      release depends on a conserved glycine residue in the HrcN phosphate-binding
      loop, which is crucial for enzymatic activity and protein function during T3S.
      There is no experimental evidence that T3S can occur in the absence of the
      ATPase, in contrast to recent findings reported for animal pathogenic bacteria.

PMID- 19114490
TI  - T-POP array identifies EcnR and PefI-SrgD as novel regulators of flagellar gene
      expression.
AB  - The T-POP transposon was employed in a general screen for tetracycline (Tet)
      induced chromosomal loci that exhibited Tet-activated or Tet-repressed expression
      of a fliC-lac transcriptional fusion. Insertions that activated flagellar
      transcription were located in flagellar genes. T-POP insertions that exhibited
      Tet-dependent fliC-lac inhibition were isolated upstream of the ecnR, fimZ, pefI
      srgD, rcsB, and ydiV genes and in the flagellar gene flgA, which is located
      upstream of the anti-sigma(28) factor gene flgM. When expressed from the
      chromosomal P(araBAD) promoter, EcnR, FimZ, PefI-SrgD, and RcsB inhibited the
      transcription of the flagellar class 1 flhDC operon. YdiV, which is weakly
      homologous to EAL domain proteins involved in cyclic-di-GMP regulation, appears
      to act at a step after class 1 transcription. By using a series of deletions of
      the regulatory genes to try to disrupt each pathway, these regulators were found
      to act largely independently of one another. These results identify EcnR and PefI
      SrgD as additional components of the complex regulatory network controlling
      flagellar expression.

PMID- 19114492
TI  - Characterization of a Coxiella burnetii ftsZ mutant generated by Himar1
      transposon mutagenesis.
AB  - Coxiella burnetii is a gram-negative obligate intracellular bacterium and the
      causative agent of human Q fever. The lack of methods to genetically manipulate
      C. burnetii significantly impedes the study of this organism. We describe here
      the cloning and characterization of a C. burnetii ftsZ mutant generated by
      mariner-based Himar1 transposon (Tn) mutagenesis. C. burnetii was
      coelectroporated with a plasmid encoding the Himar1 C9 transposase variant and a
      plasmid containing a Himar1 transposon encoding chloramphenicol
      acetyltransferase, mCherry fluorescent protein, and a ColE1 origin of
      replication. Vero cells were infected with electroporated C. burnetii and
      transformants scored as organisms replicating in the presence of chloramphenicol
      and expressing mCherry. Southern blot analysis revealed multiple transpositions
      in the C. burnetii genome and rescue cloning identified 30 and 5 insertions in
      coding and noncoding regions, respectively. Using micromanipulation, a C.
      burnetii clone was isolated containing a Tn insertion within the C terminus of
      the cell division gene ftsZ. The ftsZ mutant had a significantly lower growth
      rate than wild-type bacteria and frequently appeared as filamentous forms
      displaying incomplete cell division septa. The latter phenotype correlated with a
      deficiency in generating infectious foci on a per-genome basis compared to wild
      type organisms. The mutant FtsZ protein was also unable to bind the essential
      cell division protein FtsA. This is the first description of C. burnetii
      harboring a defined gene mutation generated by genetic transformation.

PMID- 19114491
TI  - Role of conjugative elements in the evolution of the multidrug-resistant pandemic
      clone Streptococcus pneumoniaeSpain23F ST81.
AB  - Streptococcus pneumoniae is a human commensal and pathogen able to cause a
      variety of diseases that annually result in over a million deaths worldwide. The
      S. pneumoniae(Spain23F) sequence type 81 lineage was among the first recognized
      pandemic clones and was responsible for almost 40% of penicillin-resistant
      pneumococcal infections in the United States in the late 1990s. Analysis of the
      chromosome sequence of a representative strain, and comparison with other
      available genomes, indicates roles for integrative and conjugative elements in
      the evolution of pneumococci and, more particularly, the emergence of the
      multidrug-resistant Spain 23F ST81 lineage. A number of recently acquired loci
      within the chromosome appear to encode proteins involved in the production of, or
      immunity to, antimicrobial compounds, which may contribute to the proficiency of
      this strain at nasopharyngeal colonization. However, further sequencing of other
      pandemic clones will be required to establish whether there are any general
      attributes shared by these strains that are responsible for their international
      success.

PMID- 19114493
TI  - Relative contributions of recombination and mutation to the diversification of
      the opa gene repertoire of Neisseria gonorrhoeae.
AB  - To understand the rates and mechanisms of Neisseria gonorrhoeae opa gene
      variation, the 11 opa genes were amplified independently so that an opa allelic
      profile could be defined for any isolate from the sequences at each locus. The
      opa allelic profiles from 14 unrelated isolates were all different, with no opa
      alleles shared between isolates. Examination of very closely related isolates
      from sexual contacts and sexual networks showed that these typically shared most
      opa alleles, and the mechanisms by which recent changes occurred at individual
      opa loci could be determined. The great majority of changes were due to
      recombination among existing alleles that duplicated an opa allele present at
      another locus or resulted in a mosaic of existing opa alleles. Single nucleotide
      changes or insertion/deletion of a single codon also occurred, but few of these
      events were assigned to mutation, the majority being assigned to localized
      recombination. Introduction of novel opa genes from coinfecting strains was rare,
      and all but one were observed in the same sexual network. Changes at opa loci
      occurred at a greater rate than those at the porin locus, and the opa11 locus
      changed more rapidly than other opa loci, almost always differing even between
      recent sexual contacts. Examination of the neighboring pilE gene showed that
      changes at opa11 and pilE often occurred together, although this linkage may not
      be a causal one.

PMID- 19114495
TI  - Growth phase- and cell division-dependent activation and inactivation of the
      {sigma}32 regulon in Escherichia coli.
AB  - Alternative sigma factors allow bacteria to reprogram global transcription
      rapidly and to adapt to changes in the environment. Here we report on growth- and
      cell division-dependent sigma(32) regulon activity in Escherichia coli in batch
      culture. By analyzing sigma(32) expression in growing cells, an increase in
      sigma(32) protein levels is observed during the first round of cell division
      after exit from stationary phase. Increased sigma(32) protein levels result from
      transcriptional activation of the rpoH gene. After the first round of bulk cell
      division, rpoH transcript levels and sigma(32) protein levels decrease again. The
      late-logarithmic phase and the transition to stationary phase are accompanied by
      a second increase in sigma(32) levels and enhanced stability of sigma(32) protein
      but not by enhanced transcription of rpoH. Throughout growth, sigma(32) target
      genes show expression patterns consistent with oscillating sigma(32) protein
      levels. However, during the transition to early-stationary phase, despite high
      sigma(32) protein levels, the transcription of sigma(32) target genes is
      downregulated, suggesting functional inactivation of sigma(32). It is deduced
      from these data that there may be a link between sigma(32) regulon activity and
      cell division events. Further support for this hypothesis is provided by the
      observation that in cells in which FtsZ is depleted, sigma(32) regulon activation
      is suppressed.

PMID- 19114494
TI  - Genetic evidence for the importance of protein acetylation and protein
      deacetylation in the halophilic archaeon Haloferax volcanii.
AB  - Protein acetylation and deacetylation reactions are involved in many regulatory
      processes in eukaryotes. Recently, it was found that similar processes occur in
      bacteria and archaea. Sequence analysis of the genome of the haloarchaeon
      Haloferax volcanii led to the identification of three putative protein
      acetyltransferases belonging to the Gcn5 family, Pat1, Pat2, and Elp3, and two
      deacetylases, Sir2 and HdaI. Intriguingly, the gene that encodes HdaI shares an
      operon with an archaeal histone homolog. We performed gene knockouts to determine
      whether the genes encoding these putative acetyltransferases and deacetylases are
      essential. A sir2 deletion mutant was able to grow normally, whereas an hdaI
      deletion mutant was nonviable. The latter is consistent with the finding that
      trichostatin A, a specific inhibitor of HdaI, inhibits cell growth in a
      concentration-dependent manner. We also showed that each of the
      acetyltransferases by itself is dispensable for growth but that deletion of both
      pat2 and elp3 could not be achieved. The corresponding genes are therefore
      "synthetic lethals," and the protein acetyltransferases probably have a common
      and essential substrate.

PMID- 19114496
TI  - Analysis of ColE1 MbeC unveils an extended ribbon-helix-helix family of nicking
      accessory proteins.
AB  - MbeC is a 13-kDa ColE1-encoded protein required for efficient mobilization of
      ColE1, a plasmid widely used in cloning vector technology. MbeC protein was
      purified and used for in vitro DNA binding, which showed that it binds
      specifically double-stranded DNA (dsDNA) containing the ColE1 oriT. Amino acid
      sequence comparison and secondary structure prediction imply that MbeC is related
      to the ribbon-helix-helix (RHH) protein family. Alignment with RHH members
      pointed to a conserved arginine (R13 in MbeC) that was mutated to alanine. The
      mutant MbeC(R13A) was unable to bind either single-stranded DNA or dsDNA. Limited
      proteolysis fragmented MbeC in two stable folding domains: the N-terminal domain,
      which contains the RHH motif, and the C-terminal domain, which comprises a
      signature shared by nicking accessory proteins. The results indicate that MbeC
      plays a similar role in conjugation as TraY and TrwA of plasmids F and R388,
      respectively. Thus, it appears that an extended, possibly universal mechanism of
      DNA conjugative processing exists, in which oriT-processing is carried out by
      relaxases assisted by homologous nicking accessory proteins. This mechanism seems
      to be shared by all major conjugative systems analyzed thus far.

PMID- 19114497
TI  - A regulatory network controls expression of the in vivo-expressed HreP protease
      of Yersinia enterocolitica.
AB  - The human enteropathogen Yersinia enterocolitica survives and replicates in the
      lymphoid tissues of its host. Previous in vivo analyses of gene expression
      revealed that various chromosomal genes are expressed at this stage of infection,
      but not in vitro. One of these, termed hreP, encodes a protease that is necessary
      for full virulence of Y. enterocolitica. Using transposon mutagenesis, we
      identified three genes, pypA, pypB, and pypC, as positive regulators of hreP
      transcription. PypA is an inner membrane protein with no significant similarity
      to any known proteins; PypB is a ToxR-like transmembrane transcriptional
      regulator; and PypC is a cytoplasmic transcriptional regulator with an OmpR-like
      winged helix-turn-helix DNA binding motif. We show that all Pyp proteins are able
      to activate hreP independently of each other and that PypB and PypC interact
      directly with the hreP promoter region. Furthermore, pypB and pypC are
      autoregulated and regulate each other. Additional data indicate that
      transcription of hreP is repressed by the histone-like nucleoid-structuring
      protein H-NS in a temperature-dependent manner. Our data reveal a new regulatory
      network that might have implications for the controlled expression of further
      virulence-associated functions in Yersinia.

PMID- 19114499
TI  - The cell wall regulator {sigma}I specifically suppresses the lethal phenotype of
      mbl mutants in Bacillus subtilis.
AB  - Bacterial actin homologues are thought to have a role in cell shape determination
      by positioning the cell wall synthetic machinery. They are also thought to
      control other functions, including cell polarity and chromosome segregation in
      various organisms. Bacillus subtilis and many other gram-positive bacteria have
      three actin isoforms, MreB, Mbl, and MreBH, which colocalize in helical
      structures that span the length of the cell, close to the inner surface of the
      cytoplasmic membrane. Deletion of the mbl gene has previously been reported to
      produce viable, although poorly growing, mutant cells. We now show that under
      normal conditions Deltambl cells are nonviable but suppressors allowing growth
      readily accumulate. In the presence of high concentrations of Mg(2+), viable,
      nonsuppressed mutants can be obtained. A screen for suppressor mutations revealed
      that deletion of rsgI restores Mg(2+)-independent growth of the mbl mutant.
      Recent work has shown that rsgI deletion leads to upregulation of the alternative
      sigma factor sigma(I). The basis of suppression is not yet clear, but it is
      independent of the Mg(2+) effect. We found that the construction of a triple
      mutant lacking all three actin homologues became possible in the rsgI background.
      Triple mutant cells are spherical, but no significant defect in chromosome
      segregation was detected.

PMID- 19114498
TI  - Oxygen-limiting conditions enrich for fimbriate cells of uropathogenic Proteus
      mirabilis and Escherichia coli.
AB  - MR/P fimbriae of uropathogenic Proteus mirabilis undergo invertible element
      mediated phase variation whereby an individual bacterium switches between
      expressing fimbriae (phase ON) and not expressing fimbriae (phase OFF). Under
      different conditions, the percentage of fimbriate bacteria within a population
      varies and could be dictated by either selection (growth advantage of one phase)
      or signaling (preferentially converting one phase to the other in response to
      external signals). Expression of MR/P fimbriae increases in a cell-density
      dependent manner in vitro and in vivo. However, rather than the increased cell
      density itself, this increase in fimbrial expression is due to an enrichment of
      fimbriate bacteria under oxygen limitation resulting from increased cell density.
      Our data also indicate that the persistence of MR/P fimbriate bacteria under
      oxygen-limiting conditions is a result of both selection (of MR/P fimbrial phase
      variants) and signaling (via modulation of expression of the MrpI recombinase).
      Furthermore, the mrpJ transcriptional regulator encoded within the mrp operon
      contributes to phase switching. Type 1 fimbriae of Escherichia coli, which are
      likewise subject to phase variation via an invertible element, also increase in
      expression during reduced oxygenation. These findings provide evidence to support
      a mechanism for persistence of fimbriate bacteria under oxygen limitation, which
      is relevant to disease progression within the oxygen-restricted urinary tract.

PMID- 19114500
TI  - Trypanosoma brucei UDP-glucose:glycoprotein glucosyltransferase has unusual
      substrate specificity and protects the parasite from stress.
AB  - In this paper, we describe the range of N-linked glycan structures produced by
      wild-type and glucosidase II null mutant bloodstream form Trypanosoma brucei
      parasites and the creation and characterization of a bloodstream form Trypanosoma
      brucei UDP-glucose:glycoprotein glucosyltransferase null mutant. These analyses
      highlight peculiarities of the Trypanosoma brucei UDP-glucose:glycoprotein
      glucosyltransferase, including an unusually wide substrate specificity, ranging
      from Man(5)GlcNAc(2) to Man(9)GlcNAc(2) glycans, and an unusually high efficiency
      in vivo, quantitatively glucosylating the Asn263 N-glycan of variant surface
      glycoprotein (VSG) 221 and 75% of all non-VSG N glycosylation sites. We also show
      that although Trypanosoma brucei UDP-glucose:glycoprotein glucosyltransferase is
      not essential for parasite growth at 37 degrees C, it is essential for parasite
      growth and survival at 40 degrees C. The null mutant was also shown to be
      hypersensitive to the effects of the N glycosylation inhibitor tunicamycin.
      Further analysis of bloodstream form Trypanosoma brucei under normal conditions
      and stress conditions suggests that it does not have a classical unfolded protein
      response triggered by sensing unfolded proteins in the endoplasmic reticulum.
      Rather, judging by its uniform Grp78/BiP levels, it appears to have an
      unregulated and constitutively active endoplasmic reticulum protein folding
      system. We suggest that the latter may be particularly appropriate for this
      organism, which has an extremely high flux of glycoproteins through its secretory
      pathway.

PMID- 19114501
TI  - Hypovirus-responsive transcription factor gene pro1 of the chestnut blight fungus
      Cryphonectria parasitica is required for female fertility, asexual spore
      development, and stable maintenance of hypovirus infection.
AB  - We report characterization of the gene encoding putative transcription factor
      PRO1, identified in transcriptional profiling studies as being downregulated in
      the chestnut blight fungus Cryphonectria parasitica in response to infection by
      virulence-attenuating hypoviruses. Sequence analysis confirmed that pro1 encodes
      a Zn(II)(2)Cys(6) binuclear cluster DNA binding protein with significant sequence
      similarity to the pro1 gene product that controls fruiting body development in
      Sordaria macrospora. Targeted disruption of the C. parasitica pro1 gene resulted
      in two phenotypic changes that also accompany hypovirus infection, a significant
      reduction in asexual sporulation that could be reversed by exposure to high light
      intensity, and loss of female fertility. The pro1 disruption mutant, however,
      retained full virulence. Although hypovirus CHV1-EP713 infection was established
      in the pro1 disruption mutant, infected colonies continually produced virus-free
      sectors, suggesting that PRO1 is required for stable maintenance of hypovirus
      infection. These results complement the recent characterization of the hypovirus
      responsive homologue of the Saccharomyces cerevisiae Ste12 C(2)H(2) zinc finger
      transcription factor gene, cpst12, which was shown to be required for C.
      parasitica female fertility and virulence.

PMID- 19114502
TI  - Functional analysis of protein kinase CK2 of the human malaria parasite
      Plasmodium falciparum.
AB  - Protein kinase CK2 (casein kinase 2) is a eukaryotic serine/threonine protein
      kinase with multiple substrates and roles in diverse cellular processes,
      including differentiation, proliferation, and translation. The mammalian
      holoenzyme consists of two catalytic alpha or alpha' subunits and two regulatory
      beta subunits. We report the identification and characterization of a Plasmodium
      falciparum CK2alpha orthologue, PfCK2alpha, and two PfCK2beta orthologues,
      PfCK2beta1 and PfCK2beta2. Recombinant PfCK2alpha possesses protein kinase
      activity, exhibits similar substrate and cosubstrate preferences to those of
      CK2alpha subunits from other organisms, and interacts with both of the PfCK2beta
      subunits in vitro. Gene disruption experiments show that the presence of
      PfCK2alpha is crucial to asexual blood stage parasites and thereby validate the
      enzyme as a possible drug target. PfCK2alpha is amenable to inhibitor screening,
      and we report differential susceptibility between the human and P. falciparum
      CK2alpha enzymes to a small molecule inhibitor. Taken together, our data identify
      PfCK2alpha as a potential target for antimalarial chemotherapeutic intervention.

PMID- 19114503
TI  - A new look at emotional intelligence: a dual-process framework.
AB  - In this article, the author provides a framework to guide research in emotional
      intelligence. Studies conducted up to the present bear on a conception of
      emotional intelligence as pertaining to the domain of consciousness and
      investigate the construct with a correlational approach. As an alternative, the
      author explores processes underlying emotional intelligence, introducing the
      distinction between conscious and automatic processing as a potential source of
      variability in emotionally intelligent behavior. Empirical literature is reviewed
      to support the central hypothesis that individual differences in emotional
      intelligence may be best understood by considering the way individuals
      automatically process emotional stimuli. Providing directions for research, the
      author encourages the integration of experimental investigation of processes
      underlying emotional intelligence with correlational analysis of individual
      differences and fosters the exploration of the automaticity component of
      emotional intelligence.

PMID- 19114504
TI  - Physicochemical basis for the inhibitory effects of organic and inorganic salts
      on the growth of Pectobacterium carotovorum subsp. carotovorum and Pectobacterium
      atrosepticum.
AB  - Twenty-one salts were tested for their effects on the growth of Pectobacterium
      carotovorum subsp. carotovorum and Pectobacterium atrosepticum. In liquid medium,
      11 salts (0.2 M) exhibited strong inhibition of bacterial growth. The inhibitory
      action of salts relates to the water-ionizing capacity and the lipophilicity of
      their constituent ions.

PMID- 19114505
TI  - Iron requirement for Mn(II) oxidation by Leptothrix discophora SS-1.
AB  - A common form of biocatalysis of Mn(II) oxidation results in the formation of
      biogenic Mn(III, IV) oxides and is a key reaction in the geochemical cycling of
      Mn. In this study, we grew the model Mn(II)-oxidizing bacterium Leptothrix
      discophora SS-1 in media with limited iron (0.1 microM iron/5.8 mM pyruvate) and
      sufficient iron (0.2 microM iron/5.8 mM pyruvate). The influence of iron on the
      rate of extracellular Mn(II) oxidation was evaluated. Cultures in which cell
      growth was limited by iron exhibited reduced abilities to oxidize Mn(II) compared
      to cultures in medium with sufficient iron. While the extracellular Mn(II)
      oxidizing factor (MOF) is thought to be a putative multicopper oxidase, Mn(II)
      oxidation in the presence of zero added Cu(II) was detected and the decrease in
      the observed Mn(II) oxidation rate in iron-limited cultures was not relieved when
      the medium was supplemented with Cu(II). The decline of Mn(II) oxidation under
      iron-limited conditions was not accompanied by siderophore production and is
      unlikely to be an artifact of siderophore complex formation with Mn(III). The
      temporal variations in mofA gene transcript levels under conditions of limited
      and abundant iron were similar, indicating that iron limitation did not interfere
      with the transcription of the mofA gene. Our quantitative PCR results provide a
      step forward in understanding the regulation of Mn(II) oxidation. The mechanistic
      role of iron in Mn(II) oxidation is uncertain; the data are consistent with a
      direct requirement for iron as a component of the MOF or an indirect effect of
      iron resulting from the limitation of one of many cellular functions requiring
      iron.

PMID- 19114506
TI  - DNA sequencing and homologous expression of a small peptide conferring immunity
      to gassericin A, a circular bacteriocin produced by Lactobacillus gasseri LA39.
AB  - Gassericin A, produced by Lactobacillus gasseri LA39, is a hydrophobic circular
      bacteriocin. The DNA region surrounding the gassericin A structural gene, gaaA,
      was sequenced, and seven open reading frames (ORFs) of 3.5 kbp (gaaBCADITE) were
      found with possible functions in gassericin A production, secretion, and
      immunity. The deduced products of the five consecutive ORFs gaaADITE have
      homology to those of genes involved in butyrivibriocin AR10 production, although
      the genetic arrangements are different in the two circular bacteriocin genes.
      GaaI is a small, positively charged hydrophobic peptide of 53 amino acids
      containing a putative transmembrane segment. Heterologous expression and
      homologous expression of GaaI in Lactococcus lactis subsp. cremoris MG1363 and L.
      gasseri JCM1131(T), respectively, were studied. GaaI-expressing strains exhibited
      at least sevenfold-higher resistance to gassericin A than corresponding control
      strains, indicating that gaaI encodes an immunity peptide for gassericin A.
      Comparison of GaaI to peptides with similar characteristics found in the circular
      bacteriocin gene loci is discussed.

PMID- 19114507
TI  - Anaerobic biodegradation of n-hexadecane by a nitrate-reducing consortium.
AB  - Nitrate-reducing enrichments, amended with n-hexadecane, were established with
      petroleum-contaminated sediment from Onondaga Lake. Cultures were serially
      diluted to yield a sediment-free consortium. Clone libraries and denaturing
      gradient gel electrophoresis analysis of 16S rRNA gene community PCR products
      indicated the presence of uncultured alpha- and betaproteobacteria similar to
      those detected in contaminated, denitrifying environments. Cultures were
      incubated with H(34)-hexadecane, fully deuterated hexadecane (d(34)-hexadecane),
      or H(34)-hexadecane and NaH(13)CO(3). Gas chromatography-mass spectrometry
      analysis of silylated metabolites resulted in the identification of
      [H(29)]pentadecanoic acid, [H(25)]tridecanoic acid, [1-(13)C]pentadecanoic acid,
      [3-(13)C]heptadecanoic acid, [3-(13)C]10-methylheptadecanoic acid, and d(27)
      pentadecanoic, d(25)-, and d(2)(4)-tridecanoic acids. The identification of these
      metabolites suggests a carbon addition at the C-3 position of hexadecane, with
      subsequent beta-oxidation and transformation reactions (chain elongation and C-10
      methylation) that predominantly produce fatty acids with odd numbers of carbons.
      Mineralization of [1-(14)C]hexadecane was demonstrated based on the recovery of
      (14)CO(2) in active cultures.

PMID- 19114508
TI  - Metabolism of hydroxylated and fluorinated benzoates by Syntrophus aciditrophicus
      and detection of a fluorodiene metabolite.
AB  - Transformations of 2-hydroxybenzoate and fluorobenzoate isomers were investigated
      in the strictly anaerobic Syntrophus aciditrophicus to gain insight into the
      initial steps of the metabolism of aromatic acids. 2-Hydroxybenzoate was
      metabolized to methane and acetate by S. aciditrophicus and Methanospirillum
      hungatei cocultures and reduced to cyclohexane carboxylate by pure cultures of S.
      aciditrophicus when grown in the presence of crotonate. Under both conditions,
      transient accumulation of benzoate but not phenol was observed, indicating that
      dehydroxylation occurred prior to ring reduction. Pure cultures of S.
      aciditrophicus reductively dehalogenated 3-fluorobenzoate with the stoichiometric
      accumulation of benzoate and fluorine. 3-Fluorobenzoate-degrading cultures
      produced a metabolite that had a fragmentation pattern almost identical to that
      of the trimethylsilyl (TMS) derivative of 3-fluorobenzoate but with a mass
      increase of 2 units. When cells were incubated with deuterated water, this
      metabolite had a mass increase of 3 or 4 units relative to the TMS derivative of
      3-fluorobenzoate. (19)F nuclear magnetic resonance spectroscopy ((19)F NMR)
      detected a metabolite in fluorobenzoate-degrading cultures with two double bonds,
      either 1-carboxyl-3-fluoro-2,6-cyclohexadiene or 1-carboxyl-3-fluoro-3,6
      cyclohexadiene. The mass spectral and NMR data are consistent with the addition
      of two hydrogen or deuterium atoms to 3-fluorobenzoate, forming a 3
      fluorocyclohexadiene metabolite. The production of a diene metabolite provides
      evidence that S. aciditrophicus contains dearomatizing reductase that uses two
      electrons to dearomatize the aromatic ring.

PMID- 19114509
TI  - Telomere organization in the ligninolytic basidiomycete Pleurotus ostreatus.
AB  - Telomeres are structural and functional chromosome regions that are essential for
      the cell cycle to proceed normally. They are, however, difficult to map
      genetically and to identify in genome-wide sequence programs because of their
      structure and repetitive nature. We studied the telomeric and subtelomeric
      organization in the basidiomycete Pleurotus ostreatus using a combination of
      molecular and bioinformatics tools that permitted us to determine 19 out of the
      22 telomeres expected in this fungus. The telomeric repeating unit in P.
      ostreatus is TTAGGG, and the numbers of repetitions of this unit range between 25
      and 150. The mapping of the telomere restriction fragments to linkage groups 6
      and 7 revealed polymorphisms compatible with those observed by pulsed field gel
      electrophoresis separation of the corresponding chromosomes. The subtelomeric
      regions in Pleurotus contain genes similar to those described in other eukaryotic
      systems. The presence of a cluster of laccase genes in chromosome 6 and a
      bipartite structure containing a Het-related protein and an alcohol dehydrogenase
      are especially relevant; this bipartite structure is characteristic of the
      Pezizomycotina fungi Neurospora crassa and Aspergillus terreus. As far as we
      know, this is the first report describing the presence of such structures in
      basidiomycetes and the location of a laccase gene cluster in the subtelomeric
      region, where, among others, species-specific genes allowing the organism to
      adapt rapidly to the environment usually map.

PMID- 19114510
TI  - Postgenomic analysis of streptococcus thermophilus cocultivated in milk with
      Lactobacillus delbrueckii subsp. bulgaricus: involvement of nitrogen, purine, and
      iron metabolism.
AB  - Streptococcus thermophilus is one of the most widely used lactic acid bacteria in
      the dairy industry, in particular in yoghurt manufacture, where it is associated
      with Lactobacillus delbrueckii subsp. bulgaricus. This bacterial association,
      known as a proto-cooperation, is poorly documented at the molecular and
      regulatory levels. We thus investigate the kinetics of the transcriptomic and
      proteomic modifications of S. thermophilus LMG 18311 in response to the presence
      of L. delbrueckii subsp. bulgaricus ATCC 11842 during growth in milk at two
      growth stages. Seventy-seven different genes or proteins (4.1% of total coding
      sequences), implicated mainly in the metabolism of nitrogen (24%), nucleotide
      base (21%), and iron (20%), varied specifically in coculture. One of the most
      unpredicted results was a significant decrease of most of the transcripts and
      enzymes involved in purine biosynthesis. Interestingly, the expression of nearly
      all genes potentially encoding iron transporters of S. thermophilus decreased,
      whereas that of iron-chelating dpr as well as that of the fur (perR) regulator
      genes increased, suggesting a reduction in the intracellular iron concentration,
      probably in response to H(2)O(2) production by L. bulgaricus. The present study
      reveals undocumented nutritional exchanges and regulatory relationships between
      the two yoghurt bacteria, which provide new molecular clues for the understanding
      of their associative behavior.

PMID- 19114511
TI  - Tissue-associated "Candidatus Mycoplasma corallicola" and filamentous bacteria on
      the cold-water coral Lophelia pertusa (Scleractinia).
AB  - The cold-water coral Lophelia pertusa (Scleractinia, Caryophylliidae) is a key
      species in the formation of cold-water reefs, which are among the most diverse
      deep-sea ecosystems. It occurs in two color varieties: white and red. Bacterial
      communities associated with Lophelia have been investigated in recent years, but
      the role of the associated bacteria remains largely obscure. This study uses
      catalyzed reporter deposition fluorescence in situ hybridization to detect the in
      situ location of specific bacterial groups on coral specimens from the
      Trondheimsfjord (Norway). Two tissue-associated groups were identified: (i)
      bacteria on the host's tentacle ectoderm, "Candidatus Mycoplasma corallicola,"
      are flasklike, pointed cells and (ii) endoderm-associated bona fide TM7 bacteria
      form long filaments in the gastral cavity. These tissue-bound bacteria were found
      in all coral specimens from the Trondheimsfjord, indicating a closer relationship
      with the coral compared to bacterial assemblages present in coral mucus and
      gastric fluid.

PMID- 19114512
TI  - Role of proP and proU in betaine uptake by Yersinia enterocolitica under cold and
      osmotic stress conditions.
AB  - Yersinia enterocolitica is a food-borne pathogen with the ability to grow at cold
      temperatures and tolerate high osmolarity. The bacterium tolerates osmotic stress
      by intracellular accumulation of osmolytes, such as betaine. The proP gene and
      proU operon of Y. enterocolitica were sequenced, and single (ProP(-) ProU(+) and
      ProP(+) ProU(-)) and double (ProP(-) ProU(-)) mutants were generated. Upon
      exposure to osmotic or chill stress, the single and double mutants demonstrated a
      reduction in betaine uptake compared to that in the wild type, suggesting that
      proP and proU play a role in betaine uptake during osmotic and chill stress
      responses of Y. enterocolitica.

PMID- 19114513
TI  - Molecular comparison of bacterial communities within iron-containing flocculent
      mats associated with submarine volcanoes along the Kermadec Arc.
AB  - Iron oxide sheaths and filaments are commonly found in hydrothermal environments
      and have been shown to have a biogenic origin. These structures were seen in the
      flocculent material associated with two submarine volcanoes along the Kermadec
      Arc north of New Zealand. Molecular characterization of the bacterial communities
      associated with the flocculent samples indicated that no known Fe-oxidizing
      bacteria dominated the recovered clone libraries. However, clones related to the
      recently described Fe-oxidizing bacterium Mariprofundus ferrooxydans were
      obtained from both the iron-containing flocculent (Fe-floc) and sediment samples,
      and peaks corresponding to Mariprofundus ferrooxydans, as well as the related
      clones, were observed in several of our terminal restriction fragment length
      polymorphism profiles. A large group of epsilonproteobacterial sequences, for
      which there is no cultured representative, dominated clones from the Fe-floc
      libraries and were less prevalent in the sediment sample. Phylogenetic analyses
      indicated that several operational taxonomic units appeared to be site specific,
      and statistical analyses of the clone libraries found that all samples were
      significantly different from each other. Thus, the bacterial communities in the
      Fe-floc samples were not more closely related to each other than to the sediment
      communities.

PMID- 19114514
TI  - Molecular ecology of Listeria monocytogenes: evidence for a reservoir in milking
      equipment on a dairy farm.
AB  - A longitudinal study aimed to detect Listeria monocytogenes on a New York State
      dairy farm was conducted between February 2004 and July 2007. Fecal samples were
      collected every 6 months from all lactating cows. Approximately 20 environmental
      samples were obtained every 3 months. Bulk tank milk samples and in-line milk
      filter samples were obtained weekly. Samples from milking equipment and the
      milking parlor environment were obtained in May 2007. Fifty-one of 715 fecal
      samples (7.1%) and 22 of 303 environmental samples (7.3%) were positive for L.
      monocytogenes. A total of 73 of 108 in-line milk filter samples (67.6%) and 34 of
      172 bulk tank milk samples (19.7%) were positive for L. monocytogenes. Listeria
      monocytogenes was isolated from 6 of 40 (15%) sampling sites in the milking
      parlor and milking equipment. In-line milk filter samples had a greater
      proportion of L. monocytogenes than did bulk tank milk samples (P<0.05) and
      samples from other sources (P<0.05). The proportion of L. monocytogenes-positive
      samples was greater among bulk tank milk samples than among fecal or
      environmental samples (P<0.05). Analysis of 60 isolates by pulsed-field gel
      electrophoresis (PFGE) yielded 23 PFGE types after digestion with AscI and ApaI
      endonucleases. Three PFGE types of L. monocytogenes were repeatedly found in
      longitudinally collected samples from bulk tank milk and in-line milk filters.

PMID- 19114515
TI  - Multilocus sequence typing of Oenococcus oeni: detection of two subpopulations
      shaped by intergenic recombination.
AB  - Oenococcus oeni is the acidophilic lactic acid bacterial species most frequently
      associated with malolactic fermentation of wine. Since the description of the
      species (formerly Leuconostoc oenos), characterization of indigenous strains and
      industrially produced cultures by diverse typing methods has led to divergent
      conclusions concerning the genetic diversity of strains. In the present study, a
      multilocus sequence typing (MLST) scheme based on the analysis of eight
      housekeeping genes was developed and tested on a collection of 43 strains of
      diverse origins. The eight targeted loci were successfully amplified and
      sequenced for all isolates. Only three to 11 different alleles were detected for
      these genes. The average nucleotide diversity also was rather limited (0.0011 to
      0.0370). Despite this limited allelic diversity, the combination of alleles of
      each strain disclosed 34 different sequence types, which denoted a significant
      genotypic diversity. A phylogenetic analysis of the concatenated sequences showed
      that all strains form two well distinct groups of 28 and 15 strains.
      Interestingly, the same groups were defined by pulsed-field gel electrophoresis,
      although this method targets different genetic variations. A minimum spanning
      tree analysis disclosed very few and small clonal complexes. In agreement,
      statistical analyses of MLST data suggest that recombination events were
      important during O. oeni evolution and contributed to the wide dissemination of
      alleles among strains. Taken together, our results showed that MLST is more
      efficient than pulsed-field gel electrophoresis for typing O. oeni strains, and
      they provided a picture of the O. oeni population that explains some conflicting
      results previously obtained.

PMID- 19114516
TI  - Fermentation of barley by using Saccharomyces cerevisiae: examination of barley
      as a feedstock for bioethanol production and value-added products.
AB  - The objective of this study was to examine the ethanol yield potential of three
      barley varieties (Xena, Bold, and Fibar) in comparison to two benchmarks, corn
      and wheat. Very high gravity (VHG; 30% solids) fermentations using both
      conventional and Stargen 001 enzymes for starch hydrolysis were carried out as
      simultaneous saccharification and fermentation. The grains and their
      corresponding dried distiller's grain with solubles (DDGS) were also analyzed for
      nutritional and value-added characteristics. A VHG traditional fermentation
      approach utilizing jet-cooking fermentation revealed that both dehulled Bold and
      Xena barley produced ethanol concentrations higher than that produced by wheat
      (12.3, 12.2, and 11.9%, respectively) but lower than that produced by corn
      (13.8%). VHG-modified Stargen-based fermentation of dehulled Bold barley
      demonstrated comparable performance (14.3% ethanol) relative to that of corn
      (14.5%) and wheat (13.3%). Several important components were found to survive
      fermentation and were concentrated in DDGS. The highest yield of phenolics was
      detected in the DDGS (modified Stargen 001, 20% solids) of Xena (14.6 mg of
      gallic acid/g) and Bold (15.0 mg of gallic acid/g) when the hull was not removed
      before fermentation. The highest concentration of sterols in DDGS from barley was
      found in Xena (3.9 mg/g) when the hull was included. The DDGS recovered from corn
      had the highest concentration of fatty acids (72.6 and 77.5 mg/g). The DDGS
      recovered from VHG jet-cooking fermentations of Fibar, dehulled Bold, and corn
      demonstrated similar levels of tocopherols and tocotrienols. Corn DDGS was
      highest in crude fat but was lowest in crude protein and in vitro energy
      digestibility. Wheat DDGS was highest in crude protein content, similar to
      previous studies. The barley DDGS was the highest in in vitro energy
      digestibility.

PMID- 19114517
TI  - Temporal dynamics of South End tidal creek (Sapelo Island, Georgia) bacterial
      communities.
AB  - Bacterial community dynamics in South End tidal creek, Sapelo Island, GA, were
      studied over a 74-h, five-tidal-cycle period. Observations were made hourly for
      the first consecutive 24 hours, every 3 hours on the second day, and every 6
      hours on the third day. Tide most strongly influenced bacterial community
      composition (high-tide versus low-tide community analysis of similarities, R =
      0.41, P < 0.03). Dissolved oxygen concentration and conductivity were important
      proximate drivers. However, after accounting for tide and environmental variables
      colinear with tide, cumulative time became more important in describing community
      variation. In-stream physical processes, including particulate suspension and
      sedimentation, may explain tide-associated trends in the bacterial community
      composition observed.

PMID- 19114518
TI  - Targeted engineering of the antibacterial peptide apidaecin, based on an in vivo
      monitoring assay system.
AB  - Seven mutant forms of the antibacterial peptide apidaecin with increased activity
      were created by combinatorial mutagenesis targeted to the three N-terminal amino
      acid residues that had previously been identified as a nonessential region. An in
      vitro MIC assay revealed that the amino acid substitutions in the functionally
      variable region were effective in improving differential activity toward the four
      gram-negative bacteria tested, while a gram-positive bacterium was unaffected.

PMID- 19114519
TI  - Growth-regulated expression of a bacteriocin, produced by the sweet potato
      pathogen Streptomyces ipomoeae, that exhibits interstrain inhibition.
AB  - Certain strains of the bacterial sweet potato pathogen Streptomyces ipomoeae
      produce the bacteriocin ipomicin, which inhibits other sensitive strains of the
      same species. Within the signal-sequence-encoding portion of the ipomicin
      structural gene ipoA exists a single rare TTA codon, which is recognized in
      Streptomyces bacteria by the temporally accumulating bldA leucyl tRNA. In this
      study, ipomicin was shown to stably accumulate in culture supernatants of S.
      ipomoeae in a growth-regulated manner that did not coincide with the pattern of
      ipoA expression. Similar growth-regulated production of ipomicin in Streptomyces
      coelicolor containing the cloned ipoA gene was found to be directly dependent on
      translation of the ipoA TTA codon by the bldA leucyl tRNA. The results here
      suggest that bldA-dependent translation of the S. ipomoeae ipoA gene leads to
      growth-regulated production of the ipomicin precursor, which upon processing to
      the mature form and secretion stably accumulates in the extracellular
      environment. To our knowledge, this is the first example of bldA regulation of a
      bacteriocin in the streptomycetes.

PMID- 19114521
TI  - Construction of Mycobacterium abscessus defined glycopeptidolipid mutants:
      comparison of genetic tools.
AB  - Mycobacterium abscessus is a rapidly growing mycobacterial species that can be
      involved in pulmonary and disseminated infections in immunosuppressed or young
      cystic fibrosis patients. It is an emerging pathogen and has attracted recent
      attention due to the numerous cases of infection; furthermore, genomic tools have
      been developed for this species. Nevertheless, the study of this species has
      until now been limited to spontaneous variants. We report here a comparison of
      three different mutagenesis systems--the ts-sacB, the phage, and the
      recombineering systems--and show that there are important differences in their
      efficiency for the construction of allelic-exchange mutants. We show, using the
      mmpL4b gene of the glycopeptidolipid pathway as a target, that allelic-exchange
      mutants can be constructed with a reasonable efficiency (approximately 7%) using
      the recombineering system. These observations will facilitate genetic and
      cellular microbiology experiments involving the construction and use of well
      defined mutants to study the virulence determinant of this emerging pathogen.

PMID- 19114520
TI  - Poly-N-acetylglucosamine matrix polysaccharide impedes fluid convection and
      transport of the cationic surfactant cetylpyridinium chloride through bacterial
      biofilms.
AB  - Biofilms are composed of bacterial cells encased in a self-synthesized,
      extracellular polymeric matrix. Poly-beta(1,6)-N-acetyl-d-glucosamine (PNAG) is a
      major biofilm matrix component in phylogenetically diverse bacteria. In this
      study we investigated the physical and chemical properties of the PNAG matrix in
      biofilms produced in vitro by the gram-negative porcine respiratory pathogen
      Actinobacillus pleuropneumoniae and the gram-positive device-associated pathogen
      Staphylococcus epidermidis. The effect of PNAG on bulk fluid flow was determined
      by measuring the rate of fluid convection through biofilms cultured in
      centrifugal filter devices. The rate of fluid convection was significantly higher
      in biofilms cultured in the presence of the PNAG-degrading enzyme dispersin B
      than in biofilms cultured without the enzyme, indicating that PNAG decreases bulk
      fluid flow. PNAG also blocked transport of the quaternary ammonium compound
      cetylpyridinium chloride (CPC) through the biofilms. Binding of CPC to biofilms
      further impeded fluid convection and blocked transport of the azo dye Allura red.
      Bioactive CPC was efficiently eluted from biofilms by treatment with 1 M sodium
      chloride. Taken together, these findings suggest that CPC reacts directly with
      the PNAG matrix and alters its physical and chemical properties. Our results
      indicate that PNAG plays an important role in controlling the physiological state
      of biofilms and may contribute to additional biofilm-associated processes such as
      biocide resistance.

PMID- 19114522
TI  - Oxidation of lanthionines renders the lantibiotic nisin inactive.
AB  - The peptide antibiotic nisin A belongs to the group of antibiotics called
      lantibiotics. They are classified as lantibiotics because they contain the
      structural group lanthionine. Lanthionines are composed of a single sulfur atom
      that is linked to the beta-carbons of two alanine moieties. These sulfur atoms
      are vulnerable to environmental oxidation. A mild oxidation reaction was
      performed on nisin A to determine the relative effects it would have on
      bioactivity. High-mass-accuracy Fourier transform ion cyclotron resonance mass
      spectrometry data revealed the addition of seven, eight, and nine oxygens. These
      additions correspond to the five lanthionines, two methionines, and two
      histidines that would be susceptible to oxidation. Subsequent bioassays revealed
      that the oxidized form of nisin A had a complete loss of bactericidal activity.
      In a competition study, the oxidized nisin did not appear to have an antagonistic
      affect on the bioactivity of nisin A, since the addition of an equal molar
      concentration of the oxidized variant did not have an influence on the
      bactericidal activity of the native antibiotic. Electron microscopy data revealed
      that the oxidized forms were still capable of assembling into large circular
      complexes, demonstrating that oxidation does not disrupt the lateral assembly
      mechanism of the antibiotic. Affinity thin-layer chromatography and fluorescence
      microscopy experiments suggested that the loss of activity is due to the
      inability of the oxidized form of nisin to bind to the cell wall precursor lipid
      II. Given the loss of bioactivity following oxidation, oxidation should be an
      important factor to consider in future production, purification, pharmacokinetic,
      and pharmacodynamic studies.

PMID- 19114523
TI  - Role of the Hya hydrogenase in recycling of anaerobically produced H2 in
      Salmonella enterica serovar Typhimurium.
AB  - Double and triple uptake-type hydrogenase mutants were used to determine which
      hydrogenase recycles fermentatively produced hydrogen. The Deltahyb Deltahya and
      Deltahyd Deltahya double mutants evolved H(2) at rates similar to that of the
      triple mutant strain, so Hya alone oxidizes the bulk of H(2) produced during
      fermentation. When only Hya was present, no hydrogen production was observed in
      nutrient-limited medium. H(2) uptake assays showed that Hya can oxidize both
      exogenously added H(2) and formate hydrogen lyase-evolved H(2) anaerobically.
      Even after anaerobic growth, all three uptake-type hydrogenases could function in
      the presence of oxygen, including using O(2) as a terminal acceptor.

PMID- 19114524
TI  - Phleomycin increases transformation efficiency and promotes single integrations
      in Schizophyllum commune.
AB  - Phleomycin is mutagenic by introducing double-strand breaks in DNA. The ble gene
      of Streptoalloteychus hindustanus, which confers resistance to this substance, is
      widely used as a selection marker for transformation. Schizophyllum commune grows
      on 25 microg of phleomycin ml(-1) after introduction of a resistance cassette
      based on the ble gene. However, we here report that growth of resistant colonies
      on this concentration of phleomycin resulted in aberrant colony morphologies.
      Apparently, phleomycin was mutagenic despite acquired resistance. Therefore, a
      new selection system was developed based on resistance to the antibiotic
      nourseothricin. However, the transformation efficiency was tenfold lower than
      that obtained with phleomycin as a selection agent. This low transformation
      efficiency could be rescued by addition of a nonselective concentration of
      phleomycin during protoplast regeneration. This was accompanied by a higher
      incidence of single-copy integrations and with an increase of expression of key
      genes involved in double-strand break repair. Taken together, we conclude that
      the effect of a nonselective concentration of phleomycin strongly resembles the
      effect of restriction enzyme-mediated integration (REMI) but, unlike REMI, it
      does not depend on the presence of a target restriction site.

PMID- 19114525
TI  - Molecular diversity of a North Carolina wastewater treatment plant as revealed by
      pyrosequencing.
AB  - We report the results of pyrosequencing of DNA collected from the activated
      sludge basin of a wastewater treatment plant in Charlotte, NC. Using the 454-FLX
      technology, we generated 378,601 sequences with an average read length of 250.4
      bp. Running the 454 assembly algorithm over our sequences yielded very poor
      assembly, with only 0.3% of our sequences participating in assembly of
      significant contigs. Of the 117 contigs greater than 500 bp long that were
      assembled, the most common annotations were to transposases and hypothetical
      proteins. Comparing our sequences to known microbial genomes showed nonspecific
      recruitment, indicating that previously described taxa are only distantly related
      to the most abundant microbes in this treatment plant. A comparison of proteins
      generated by translating our sequence set to translations of other sequenced
      microbiomes shows a distinct metabolic profile for activated sludge with high
      counts for genes involved in metabolism of aromatic compounds and low counts for
      genes involved in photosynthesis. Taken together, these data document the
      substantial levels of microbial diversity within activated sludge and further
      establish the great utility of pyrosequencing for investigating diversity in
      complex ecosystems.

PMID- 19114526
TI  - Acid and base stress and transcriptomic responses in Bacillus subtilis.
AB  - Acid and base environmental stress responses were investigated in Bacillus
      subtilis. B. subtilis AG174 cultures in buffered potassium-modified Luria broth
      were switched from pH 8.5 to pH 6.0 and recovered growth rapidly, whereas
      cultures switched from pH 6.0 to pH 8.5 showed a long lag time. Log-phase
      cultures at pH 6.0 survived 60 to 100% at pH 4.5, whereas cells grown at pH 7.0
      survived <15%. Cells grown at pH 9.0 survived 40 to 100% at pH 10, whereas cells
      grown at pH 7.0 survived <5%. Thus, growth in a moderate acid or base induced
      adaptation to a more extreme acid or base, respectively. Expression indices from
      Affymetrix chip hybridization were obtained for 4,095 protein-encoding open
      reading frames of B. subtilis grown at external pH 6, pH 7, and pH 9. Growth at
      pH 6 upregulated acetoin production (alsDS), dehydrogenases (adhA, ald, fdhD, and
      gabD), and decarboxylases (psd and speA). Acid upregulated malate metabolism
      (maeN), metal export (czcDO and cadA), oxidative stress (catalase katA; OYE
      family namA), and the SigX extracytoplasmic stress regulon. Growth at pH 9
      upregulated arginine catabolism (roc), which generates organic acids, glutamate
      synthase (gltAB), polyamine acetylation and transport (blt), the K(+)/H(+)
      antiporter (yhaTU), and cytochrome oxidoreductases (cyd, ctaACE, and qcrC). The
      SigH, SigL, and SigW regulons were upregulated at high pH. Overall, greater
      genetic adaptation was seen at pH 9 than at pH 6, which may explain the lag time
      required for growth shift to high pH. Low external pH favored dehydrogenases and
      decarboxylases that may consume acids and generate basic amines, whereas high
      external pH favored catabolism-generating acids.

PMID- 19114527
TI  - Intraspecies genomic diversity and natural population structure of the meat-borne
      lactic acid bacterium Lactobacillus sakei.
AB  - Lactobacillus sakei is a food-borne bacterium naturally found in meat and fish
      products. A study was performed to examine the intraspecies diversity among 73
      isolates sourced from laboratory collections in several different countries.
      Pulsed-field gel electrophoresis analysis demonstrated a 25% variation in genome
      size between isolates, ranging from 1,815 kb to 2,310 kb. The relatedness between
      isolates was then determined using a PCR-based method that detects the possession
      of 60 chromosomal genes belonging to the flexible gene pool. Ten different strain
      clusters were identified that had noticeable differences in their average genome
      size reflecting the natural population structure. The results show that many
      different genotypes may be isolated from similar types of meat products,
      suggesting a complex ecological habitat in which intraspecies diversity may be
      required for successful adaptation. Finally, proteomic analysis revealed a slight
      difference between the migration patterns of highly abundant GapA isoforms of the
      two prevailing L. sakei subspecies (sakei and carnosus). This analysis was used
      to affiliate the genotypic clusters with the corresponding subspecies. These
      findings reveal for the first time the extent of intraspecies genomic diversity
      in L. sakei. Consequently, identification of molecular subtypes may in the future
      prove valuable for a better understanding of microbial ecosystems in food
      products.

PMID- 19114528
TI  - Pichia anomala DBVPG 3003 secretes a ubiquitin-like protein that has
      antimicrobial activity.
AB  - The yeast strain Pichia anomala DBVPG 3003 secretes a killer toxin (Pikt) that
      has antifungal activity against Brettanomyces/Dekkera sp. yeasts. Pikt interacts
      with beta-1,6-glucan, consistent with binding to the cell wall of sensitive
      targets. In contrast to that of toxin K1, secreted by Saccharomyces cerevisiae,
      Pikt killer activity is not mediated by an increase in membrane permeability.
      Purification of the toxin yielded a homogeneous protein of about 8 kDa, which
      showed a marked similarity to ubiquitin in terms of molecular mass and N-terminal
      sequences. Pikt is also specifically recognized by anti-bovine ubiquitin
      antibodies and, similar to ubiquitin-like peptides, is not absorbed by DEAE
      cellulose. However, Pikt differs from ubiquitin in its sensitivity to proteolytic
      enzymes. Therefore, Pikt appears to be a novel ubiquitin-like peptide that has
      killer activity.

PMID- 19114530
TI  - Poultry-associated Salmonella enterica subsp. enterica serovar 4,12:d:- reveals
      high clonality and a distinct pathogenicity gene repertoire.
AB  - A European baseline survey during the years 2005 and 2006 has revealed that the
      monophasic Salmonella enterica subsp. enterica serovar 4,12:d:- was, with a
      prevalence of 23.6%, the most frequently isolated serovar in German broiler
      flocks. In Denmark and the United Kingdom, its serovar prevalences were 15.15%
      and 2.8%, respectively. Although poultry is a major source of human
      salmonellosis, serovar 4,12:d:- is rarely isolated in humans (approximately 0.09%
      per year). Molecular typing studies using pulsed-field gel electrophoresis and
      DNA microarray analysis show that the serovar is highly clonal and lacks genes
      with known contributions to pathogenicity. In contrast to other poultry
      associated serovars, all strains were susceptible to 17 antimicrobial agents
      tested and did not encode any resistance determinant. Furthermore, serovar
      4,12:d:- lacked the genes involved in galactonate metabolism and in the
      glycolysis and glyconeogenesis important for energy production in the cells. The
      conclusion of the study is that serovar 4,12:d:- seems to be primarily adapted to
      broilers and therefore causes only rare infections in humans.

PMID- 19114529
TI  - High-level diversity of dinoflagellates in the natural environment, revealed by
      assessment of mitochondrial cox1 and cob genes for dinoflagellate DNA barcoding.
AB  - DNA barcoding is a diagnostic technique for species identification using a short,
      standardized DNA. An effective DNA barcoding marker would be very helpful for
      unraveling the poorly understood species diversity of dinoflagellates in the
      natural environment. In this study, the potential utility for DNA barcoding of
      mitochondrial cytochrome c oxidase 1 (cox1) and cytochrome b (cob) was assessed.
      Among several primer sets examined, the one amplifying a 385-bp cob fragment was
      most effective for dinoflagellates. This short cob fragment is easy to sequence
      and yet possess reasonable taxon resolution. While the lack of a uniform gap
      between interspecific and intraspecific distances poses difficulties in
      establishing a phylum-wide species-discriminating distance threshold, the
      variability of cob allows recognition of species within particular lineages. The
      potential of this cob fragment as a dinoflagellate species marker was further
      tested by applying it to an analysis of the dinoflagellate assemblages in Long
      Island Sound (LIS) and Mirror Lake in Connecticut. In LIS, a highly diverse
      assemblage of dinoflagellates was detected. Some taxa can be identified to the
      species and some to the genus level, including a taxon distinctly related to the
      bipolar species Polarella glacialis, and the large number of others cannot be
      clearly identified, due to the inadequate database. In Mirror Lake, a Ceratium
      species and an unresolved taxon were detected, exhibiting a temporal transition
      from one to the other. We demonstrate that this 385-bp cob fragment is promising
      for lineage-wise dinoflagellate species identification, given an adequate
      database.

PMID- 19114532
TI  - The plant phenolic compound p-coumaric acid represses gene expression in the
      Dickeya dadantii type III secretion system.
AB  - The type III secretion system (T3SS) is a major virulence factor in many gram
      negative bacterial pathogens. This secretion system translocates effectors
      directly into the cytosol of eukaryotic host cells, where the effector proteins
      facilitate bacterial pathogenesis by interfering with host cell signal
      transduction and other cellular processes. Plants defend themselves against
      bacterial pathogens by recognizing either the type 3 effectors or their actions
      and initiating a cascade of defense responses that often results in programmed
      cell death of the plant cell being attacked. Here we show that a plant phenolic
      compound, p-coumaric acid (PCA), represses the expression of T3SS genes of the
      plant pathogen Dickeya dadantii, suggesting that plants can also defend against
      bacterial pathogens by manipulating the expression of the T3SS. PCA repressed the
      expression of T3SS regulatory genes through the HrpX/Y two-component system, a
      core regulator of the T3SS, rather than through the global regulator GacS/A,
      which indirectly regulates the T3SS. A further analysis of several PCA analogs
      suggests that the para positioning of the hydroxyl group in the phenyl ring and
      the double bond of PCA may be important for its biological activity.

PMID- 19114533
TI  - Cydia pomonella granulovirus genotypes overcome virus resistance in the codling
      moth and improve virus efficiency by selection against resistant hosts.
AB  - Cydia pomonella granulovirus (CpGV) has been used for 15 years as a
      bioinsecticide in codling moth (Cydia pomonella) control. In 2004, some insect
      populations with low susceptibility to the virus were detected for the first time
      in southeast France. RGV, a laboratory colony of codling moths resistant to the
      CpGV-M isolate used in the field, was established with collection of resistant
      insects in the field followed by an introgression of the resistant trait into a
      susceptible colony (Sv). The resistance level (based on the 50% lethal
      concentrations [LC(50)s]) of the RGV colony to the CpGV-M isolate, the active
      ingredient in all commercial virus formulations in Europe, appeared to be over
      60,000-fold compared to the Sv colony. The efficiency of CpGV isolates from
      various other regions was tested on RGV. Among them, two isolates (I12 and NPP
      R1) presented an increased pathogenicity on RGV. I12 had already been identified
      as effective against a resistant C. pomonella colony in Germany and was observed
      to partially overcome the resistance in the RGV colony. The recently identified
      isolate NPP-R1 showed an even higher pathogenicity on RGV than other isolates,
      with an LC(50) of 166 occlusion bodies (OBs)/microl, compared to 1.36 x 10(6)
      OBs/microl for CpGV-M. Genetic characterization showed that NPP-R1 is a mixture
      of at least two genotypes, one of which is similar to CpGV-M. The 2016-r4 isolate
      obtained from four successive passages of NPP-R1 in RGV larvae had a sharply
      reduced proportion of the CpGV-M-like genotype and an increased pathogenicity
      against insects from the RGV colony.

PMID- 19114534
TI  - Characterization of two novel alpha-glucosidases from Bifidobacterium breve
      UCC2003.
AB  - Two alpha-glucosidase-encoding genes (agl1 and agl2) from Bifidobacterium breve
      UCC2003 were identified and characterized. Based on their similarity to
      characterized carbohydrate hydrolases, the Agl1 and Agl2 enzymes are both
      assigned to a subgroup of the glycosyl hydrolase family 13, the alpha-1,6
      glucosidases (EC 3.2.1.10). Recombinant Agl1 and Agl2 into which a His(12)
      sequence was incorporated (Agl1(His) and Agl2(His), respectively) exhibited
      hydrolytic activity towards panose, isomaltose, isomaltotriose, and four sucrose
      isomers--palatinose, trehalulose, turanose, and maltulose--while also degrading
      trehalose and, to a lesser extent, nigerose. The preferred substrates for both
      enzymes were panose, isomaltose, and trehalulose. Furthermore, the pH and
      temperature optima for both enzymes were determined, showing that Agl1(His)
      exhibits higher thermo and pH optima than Agl2(His). The two purified alpha-1,6
      glucosidases were also shown to have transglycosylation activity, synthesizing
      oligosaccharides from palatinose, trehalulose, trehalose, panose, and
      isomaltotriose.

PMID- 19114536
TI  - Guard cell proteome reveals signals and surprises.

PMID- 19114531
TI  - Diversity and stratification of archaea in a hypersaline microbial mat.
AB  - The Guerrero Negro (GN) hypersaline microbial mats have become one focus for
      biogeochemical studies of stratified ecosystems. The GN mats are found beneath
      several of a series of ponds of increasing salinity that make up a solar saltern
      fed from Pacific Ocean water pumped from the Laguna Ojo de Liebre near GN, Baja
      California Sur, Mexico. Molecular surveys of the laminated photosynthetic
      microbial mat below the fourth pond in the series identified an enormous
      diversity of bacteria in the mat, but archaea have received little attention. To
      determine the bulk contribution of archaeal phylotypes to the pond 4 study site,
      we determined the phylogenetic distribution of archaeal rRNA gene sequences in
      PCR libraries based on nominally universal primers. The ratios of
      bacterial/archaeal/eukaryotic rRNA genes, 90%/9%/1%, suggest that the archaeal
      contribution to the metabolic activities of the mat may be significant. To
      explore the distribution of archaea in the mat, sequences derived using archaeon
      specific PCR primers were surveyed in 10 strata of the 6-cm-thick mat. The
      diversity of archaea overall was substantial albeit less than the diversity
      observed previously for bacteria. Archaeal diversity, mainly euryarchaeotes, was
      highest in the uppermost 2 to 3 mm of the mat and decreased rapidly with depth,
      where crenarchaeotes dominated. Only 3% of the sequences were specifically
      related to known organisms including methanogens. While some mat archaeal clades
      corresponded with known chemical gradients, others did not, which is likely
      explained by heretofore-unrecognized gradients. Some clades did not segregate by
      depth in the mat, indicating broad metabolic repertoires, undersampling, or both.

PMID- 19114539
TI  - The skeletal phenotypes of TRalpha and TRbeta mutant mice.
AB  - Analysis of mice harbouring deletions or mutations of T(3) receptor alpha
      (TRalpha) and beta (TRbeta) have clarified the complex relationship between
      central and peripheral thyroid status and emphasised the essential but
      contrasting roles of T(3) in skeletal development and adult bone. These studies
      indicate that TRalpha1 is the predominant TR expressed in bone and that T(3)
      exerts anabolic actions during growth but catabolic actions in the adult
      skeleton. Examination of key skeletal regulatory pathways in TR mutant mice has
      identified GH, IGF-1 and fibroblast growth factor signalling and the Indian
      hedgehog/parathyroid hormone-related peptide feedback loop as major targets of
      T(3) action in chondrocytes and osteoblasts. Nevertheless, although increased
      osteoclastic resorption is a major feature of thyrotoxic bone loss and altered
      osteoclast activity is central to the skeletal phenotype of TR mutant mice, it
      remains unclear whether T(3) has direct actions in osteoclasts. Detailed future
      analysis of the molecular mechanisms of T(3) action in bone will enhance our
      understanding of this emerging field and has the potential to identify novel
      strategies for the prevention and treatment of osteoporosis.

PMID- 19114538
TI  - Functional proteomics of Arabidopsis thaliana guard cells uncovers new stomatal
      signaling pathways.
AB  - We isolated a total of 3 x 10(8) guard cell protoplasts from 22,000 Arabidopsis
      thaliana plants and identified 1734 unique proteins using three complementary
      proteomic methods: protein spot identification from broad and narrow pH range two
      dimensional (2D) gels, and 2D liquid chromatography-matrix assisted laser
      desorption/ionization multidimensional protein identification technology. This
      extensive single-cell-type proteome includes 336 proteins not previously
      represented in transcriptome analyses of guard cells and 52 proteins classified
      as signaling proteins by Gene Ontology analysis, of which only two have been
      previously assessed in the context of guard cell function. THIOGLUCOSIDE
      GLUCOHYDROLASE1 (TGG1), a myrosinase that catalyzes the production of toxic
      isothiocyanates from glucosinolates, showed striking abundance in the guard cell
      proteome. tgg1 mutants were hyposensitive to abscisic acid (ABA) inhibition of
      guard cell inward K(+) channels and stomatal opening, revealing that the
      glucosinolate-myrosinase system, previously identified as a defense against
      biotic invaders, is required for key ABA responses of guard cells. Our results
      also suggest a mechanism whereby exposure to abiotic stresses may enhance plant
      defense against subsequent biotic stressors and exemplify how enhanced knowledge
      of the signaling networks of a specific cell type can be gained by proteomics
      approaches.

PMID- 19114540
TI  - Iodine levels and thyroid hormones in healthy pregnant women and birth weight of
      their offspring.
AB  - INTRODUCTION: The fetus is most vulnerable to severe iodine deficiency and
      hypothyroidism during pregnancy. The effects of mild iodine deficiency and
      subclinical hypothyroidism are poorly known. The present study assesses the
      association between thyroid hormones (TH)s and urinary iodine concentration (UIC)
      in healthy pregnant women and the birth weight of their children. METHODS: About
      657 pregnant women were recruited in Sabadell and followed until delivery. The
      association between THs during the first trimester, UIC during the first and
      third trimesters, and birth weight was studied in 557, 251, and 528 mother
      newborn pairs respectively, using linear and logistic regression models adjusted
      for potential confounders. Only 239 women had all the data available (thyroid
      function and UIC at the first and third trimesters). Six percent of newborns were
      classified as small for gestational age (SGA). RESULTS: The median UIC was 95 and
      104 microg/l during the first and third trimesters respectively. Women with the
      third trimester UICs between 100 and 149 microg/l had lower risk of having an SGA
      newborn than women with UICs below 50 microg/l (adjusted OR (95%CI): 0.15 (0.03
      0.76). There was no significant reduction in SGA among mothers with higher UICs.
      Lower free thyroxine and higher TSH levels during the first trimester were not
      associated with birth weight or SGA. Nevertheless, the analyses were repeated
      including only those women with all the data available, and high TSH levels
      became statistically significantly associated with lower birth weight and higher
      risk of SGA. CONCLUSIONS: The present study suggests that iodine status during
      pregnancy may be related to prenatal growth in healthy women.

PMID- 19114541
TI  - A case of cocaine-induced panhypopituitarism with human neutrophil elastase
      specific anti-neutrophil cytoplasmic antibodies.
AB  - OBJECTIVE: To describe a patient with cocaine-induced panhypopituitarism
      associated with human neutrophil elastase-anti-neutrophil cytoplasmic antibodies
      (HNE-ANCA). CASE: A 41-year-old man presented with extreme fatigue, cold
      intolerance and anorexia with 20 kg weight loss in the last 6 months. His medical
      history was unremarkable. He snorted cocaine twice a week during the last 6
      years. On examination, we saw a pale and skinny man, with a normal blood
      pressure. Because of the severity of symptoms central hypothyroidism was
      suspected and very low values of TSH, free thyroxine and free triiodothyronine
      were measured. His FSH, LH, ACTH, cortisol, prolactin and testosterone levels
      were also low. Magnetic resonance imaging and computed tomography scan showed a
      normal-sized pituitary gland entirely embedded in a dense, oedematous, contrast
      enhancing mass, and a total destruction of the nasal septum with the absence of
      conchae and severely impaired sinus walls. A transnasal biopsy showed an acute
      necrotising, non-specific and non-granulomatous inflammation. Although cocaine
      induced panhypopituitarism was suspected, Wegener's granulomatosis could not be
      excluded. Serology on ANCA showed a strongly positive C-ANCA titre (320 U/l) with
      specificity for HNE. A cocaine-induced HNE-ANCA-associated panhypopituitarism was
      diagnosed. Our patient was advised to quit using cocaine immediately and was
      initially treated with glucocorticoids and testosterone, followed by thyroxine.
      This led to a dramatic clinical response with an increase of appetite, weight
      gain and regained energy. After 2 years, the patient is well and his ANCA titre
      is no longer positive. CONCLUSION: We describe the first documented case of
      cocaine-induced panhypopituitarism associated with HNE-specific ANCA.

PMID- 19114542
TI  - Decrease of brachial-ankle pulse wave velocity in female subclinical hypothyroid
      patients during normalization of thyroid function: a double-blind, placebo
      controlled study.
AB  - OBJECTIVE: Subclinical hypothyroidism affects 5-15% of the general population, is
      especially prevalent in females, and may be associated with increased morbidity
      from cardiovascular disease, although it remains controversial. We recently
      reported a significant increase in the brachial-ankle pulse wave velocity
      (baPWV), a parameter of arterial stiffening and an independent predictor of
      cardiovascular events, in subclinical hypothyroidism without thyroiditis. The
      current study was performed to assess changes in baPWV in female subclinical
      hypothyroidism with autoimmune chronic thyroiditis (Hashimoto's disease) after
      restoration of normal thyroid function. METHODS: In a randomized placebo
      controlled study, 95 female subclinical hypothyroid patients were monitored for
      changes in baPWV before and after levothyroxine (l-T(4)) replacement therapy.
      Changes in baPWV were also measured in 42 age-matched normal female subjects.
      RESULTS: The baseline baPWV values in patients with subclinical hypothyroidism
      were significantly higher than in normal subjects. With attainment of
      euthyroidism, baPWV showed a significant decrease from 1776.7+/-86.0 to 1674.3+/
      79.2 cm/s (P=0.006) in patients treated with l-T(4), but the changes in baPWV and
      TSH were not correlated. The change in baPWV was significantly and negatively
      correlated with age and baseline pulse pressure, but multiple regression analysis
      revealed that these parameters failed to be associated with the change in baPWV.
      CONCLUSIONS: Sustained normalization of thyroid function during l-T(4)
      replacement therapy significantly decreases baPWV in female subclinical
      hypothyroid patients with autoimmune chronic thyroiditis, suggesting the
      improvement of arterial stiffening and, consequently, possible prevention of
      cardiovascular disease.

PMID- 19114543
TI  - Efficacy of a vaccine based on protective antigen and killed spores against
      experimental inhalational anthrax.
AB  - Protective antigen (PA)-based anthrax vaccines acting on toxins are less
      effective than live attenuated vaccines, suggesting that additional antigens may
      contribute to protective immunity. Several reports indicate that capsule or spore
      associated antigens may enhance the protection afforded by PA. Addition of
      formaldehyde-inactivated spores (FIS) to PA (PA-FIS) elicits total protection
      against cutaneous anthrax. Nevertheless, vaccines that are effective against
      cutaneous anthrax may not be so against inhalational anthrax. The aim of this
      work was to optimize immunization with PA-FIS and to assess vaccine efficacy
      against inhalational anthrax. We assessed the immune response to recombinant
      anthrax PA from Bacillus anthracis (rPA)-FIS administered by various immunization
      protocols and the protection provided to mice and guinea pigs infected through
      the respiratory route with spores of a virulent strain of B. anthracis. Combined
      subcutaneous plus intranasal immunization of mice yielded a mucosal
      immunoglobulin G response to rPA that was more than 20 times higher than that in
      lung mucosal secretions after subcutaneous vaccination. The titers of toxin
      neutralizing antibody and antispore antibody were also significantly higher: nine
      and eight times higher, respectively. The optimized immunization elicited total
      protection of mice intranasally infected with the virulent B. anthracis strain
      17JB. Guinea pigs were fully protected, both against an intranasal challenge with
      100 50% lethal doses (LD(50)) and against an aerosol with 75 LD(50) of spores of
      the highly virulent strain 9602. Conversely, immunization with PA alone did not
      elicit protection. These results demonstrate that the association of PA and
      spores is very much more effective than PA alone against experimental
      inhalational anthrax.

PMID- 19114544
TI  - Phosphoethanolamine substitution of lipid A and resistance of Neisseria
      gonorrhoeae to cationic antimicrobial peptides and complement-mediated killing by
      normal human serum.
AB  - The capacity of Neisseria gonorrhoeae to cause disseminated gonococcal infection
      requires that such strains resist the bactericidal action of normal human serum.
      The bactericidal action of normal human serum against N. gonorrhoeae is mediated
      by the classical complement pathway through an antibody-dependent mechanism. The
      mechanism(s) by which certain strains of gonococci resist normal human serum is
      not fully understood, but alterations in lipooligosaccharide structure can affect
      such resistance. During an investigation of the biological significance of
      phosphoethanolamine extensions from lipooligosaccharide, we found that
      phosphoethanolamine substitutions from the heptose II group of the
      lipooligosaccharide beta-chain did not impact levels of gonococcal (strain FA19)
      resistance to normal human serum or polymyxin B. However, loss of
      phosphoethanolamine substitution from the lipid A component of
      lipooligosaccharide, due to insertional inactivation of lptA, resulted in
      increased gonococcal susceptibility to polymyxin B, as reported previously for
      Neisseria meningitidis. In contrast to previous reports with N. meningitidis,
      loss of phosphoethanolamine attached to lipid A rendered strain FA19 susceptible
      to complement killing. Serum killing of the lptA mutant occurred through the
      classical complement pathway. Both serum and polymyxin B resistance as well as
      phosphoethanolamine decoration of lipid A were restored in the lptA-null mutant
      by complementation with wild-type lptA. Our results support a role for lipid A
      phosphoethanolamine substitutions in resistance of this strict human pathogen to
      innate host defenses.

PMID- 19114545
TI  - Capsule polysaccharide conjugate vaccine against diarrheal disease caused by
      Campylobacter jejuni.
AB  - The capsule polysaccharide (CPS) of Campylobacter jejuni is one of the few
      identified virulence determinants of this important human pathogen. Since CPS
      conjugate vaccines have been so effective against other mucosal pathogens, we
      evaluated this approach using CPSs from two strains of C. jejuni, 81-176 (HS23
      and HS36 serotype complex) and CG8486 (HS4 serotype complex). The CPSs of 81-176
      and CG8486 were independently linked to the carrier protein CRM(197) by reductive
      amination between an aldehyde(s), strategically created at the nonreducing end of
      each CPS, and accessible amines of CRM(197). In both cases, the CPS:CRM(197)
      ratio used was 2:1 by weight. Mass spectrometry and gel electrophoresis showed
      that on average, each glycoconjugate preparation contained, at least in part, two
      to five CPSs attached to one CRM(197). When administered subcutaneously to mice,
      these vaccines elicited robust immune responses and significantly reduced the
      disease following intranasal challenge with the homologous strains of C. jejuni.
      The CPS(81-176)-CRM(197) vaccine also provided 100% protection against diarrhea
      in the New World monkey Aotus nancymaae following orogastric challenge with C.
      jejuni 81-176.

PMID- 19114546
TI  - Role of complement in protection against Cryptococcus gattii infection.
AB  - Previous studies have shown that the alternative pathway of complement activation
      plays an important role in protection against infection with Cryptococcus
      neoformans. Cryptococcus gattii does not activate the alternative pathway as well
      as C. neoformans in vitro. The role of complement in C. gattii infection in vivo
      has not been reported. In this study, we used mice deficient in complement
      components to investigate the role of complement in protection against a C.
      gattii isolate from an ongoing outbreak in northwestern North America. While
      factor B-deficient mice showed an enhanced rate of death, complement component C3
      deficient mice died even more rapidly, indicating that the alternative pathway
      was not the only complement pathway contributing to protection against disease.
      Both C3- and factor B-deficient mice had increased fungal burdens in comparison
      to wild-type mice. Histopathology revealed an overwhelming fungal burden in the
      lungs of these complement-deficient mice, which undoubtedly prevented efficient
      gas exchange, causing death. Following the fate of radiolabeled organisms showed
      that both factor B- and C3-deficient mice were less effective than wild-type mice
      in clearing organisms. However, opsonization of C. gattii with complement
      components was not sufficient to prolong life in mice deficient in complement.
      Killing of C. gattii by macrophages in vitro was decreased in the presence of
      serum from factor B- and C3-deficient versus wild-type mice. In conclusion, we
      have demonstrated that complement activation is crucial for survival in C. gattii
      infection. Additionally, we have shown that the alternative pathway of complement
      activation is not the only complement pathway contributing to protection.

PMID- 19114547
TI  - Porphyromonas gingivalis RgpA-Kgp proteinase-adhesin complexes penetrate gingival
      tissue and induce proinflammatory cytokines or apoptosis in a concentration
      dependent manner.
AB  - The RgpA-Kgp proteinase-adhesin complexes of Porphyromonas gingivalis were
      observed, using immunostaining, in human gingival tissue associated with
      periodontitis but not in healthy tissue. The staining pattern suggested a
      concentration gradient from the subgingival plaque into the subjacent gingival
      connective tissue. Intense immunostaining was observed in areas displaying gross
      disturbance of tissue architecture. P. gingivalis cells and the RgpA-Kgp
      complexes at low concentrations were shown to stimulate secretory intercellular
      adhesion molecule 1, interleukin-8 (IL-8), IL-6, and macrophage chemoattractant
      protein secretion from cultured human epithelial (KB) and fibroblast (MRC-5)
      cells. However, at high concentrations a reduction in the level of these
      mediators was observed. In contrast, macrophage inflammatory protein 1alpha and
      IL-1alpha were stimulated only at high P. gingivalis cell concentrations. P.
      gingivalis cells and the RgpA-Kgp complexes were shown to induce apoptosis in KB
      and MRC-5 cells in a time- and dose-dependent manner. These data suggest that the
      RgpA-Kgp complexes penetrate the gingival connective tissue; at low
      concentrations distal from the plaque the complexes stimulate the secretion of
      proinflammatory mediators, while at high concentrations proximal to the plaque
      they induce apoptosis and attenuate the secretion of proinflammatory mediators.

PMID- 19114548
TI  - A strain-specific catalase mutation and mutation of the metal-binding transporter
      gene mntC attenuate Neisseria gonorrhoeae in vivo but not by increasing
      susceptibility to oxidative killing by phagocytes.
AB  - The hallmark of gonorrhea is an intense inflammatory response that is
      characterized by polymorphonuclear leukocytes (PMNs) with intracellular
      gonococci. A redundancy of defenses may protect Neisseria gonorrhoeae from
      phagocyte-derived reactive oxygen species. Here we showed that a gonococcal
      catalase (kat) mutant in strain MS11 was more sensitive to H(2)O(2) than mutants
      in cytochrome c peroxidase (ccp), methionine sulfoxide reductase (msrA), or the
      metal-binding protein (mntC) of the MntABC transporter. kat ccp and kat ccp mntC
      mutants were significantly more sensitive to H(2)O(2) than mutants in any single
      factor. None of the mutants showed increased susceptibility to murine PMNs.
      Recovery of the mntC and kat ccp mntC mutants from the lower genital tract of
      BALB/c mice, but not the kat or kat ccp mutants, was significantly reduced
      relative to wild-type bacteria. Interestingly, unlike the MS11 kat mutant, a kat
      mutant of strain FA1090 was attenuated during competitive infection with wild
      type FA1090 bacteria. The FA1090 kat mutant and MS11 mntC mutant were also
      attenuated in mice that are unable to generate a phagocytic respiratory burst. We
      conclude that inactivation of three well-characterized antioxidant genes (kat,
      ccp, and mntC) does not increase gonococcal susceptibility to the phagocytic
      respiratory burst during infection and that gonococcal catalase and the MntC
      protein confer an unidentified advantage in vivo. In the case of catalase, this
      advantage is strain specific. Finally, we also showed that an msrA mutant of
      strain MS11 demonstrated delayed attenuation in BALB/c but not C57BL/6 mice.
      Therefore, MsrA/B also appears to play a role in infection that is dependent on
      host genetic background.

PMID- 19114549
TI  - Immune evasion of leptospira species by acquisition of human complement regulator
      C4BP.
AB  - Leptospirosis is a spirochetal zoonotic disease of global distribution with a
      high incidence in tropical regions. In the last 15 years it has been recognized
      as an important emerging infectious disease due to the occurrence of large
      outbreaks in warm-climate countries and, occasionally, in temperate regions.
      Pathogenic leptospires efficiently colonize target organs after penetrating the
      host. Their invasiveness is attributed to the ability to multiply in blood,
      adhere to host cells, and penetrate into tissues. Therefore, they must be able to
      evade the innate host defense. The main purpose of the present study was to
      evaluate how several Leptospira strains evade the protective function of the
      complement system. The serum resistance of six Leptospira strains was analyzed.
      We demonstrate that the pathogenic strain isolated from infected hamsters avoids
      serum bactericidal activity more efficiently than the culture-attenuated or the
      nonpathogenic Leptospira strains. Moreover, both the alternative and the
      classical pathways of complement seem to be responsible for the killing of
      leptospires. Serum-resistant and serum-intermediate strains are able to bind
      C4BP, whereas the serum-sensitive strain Patoc I is not. Surface-bound C4BP
      promotes factor I-mediated cleavage of C4b. Accordingly, we found that pathogenic
      strains displayed reduced deposition of the late complement components C5 to C9
      upon exposure to serum. We conclude that binding of C4BP contributes to
      leptospiral serum resistance against host complement.

PMID- 19114550
TI  - The human SPT20-containing SAGA complex plays a direct role in the regulation of
      endoplasmic reticulum stress-induced genes.
AB  - One of the central questions in eukaryotic transcription is how activators can
      transmit their signal to stimulate gene expression in the context of chromatin.
      The multisubunit SAGA coactivator complex has both histone acetyltransferase and
      deubiquitination activities and remodels chromatin to allow transcription.
      Whether and how SAGA is able to regulate transcription at specific loci is poorly
      understood. Using mass spectrometry, immunoprecipitation, and Western blot
      analysis, we have identified human SPT20 (hSPT20) as the human homologue of the
      yeast Spt20 and show that hSPT20 is a bona fide subunit of the human SAGA (hSAGA;
      previously called TFTC/STAGA/PCAF) complex and that hSPT20 is required for the
      integrity of the hSAGA complex. We demonstrate that hSPT20 and other hSAGA
      subunits, together with RNA polymerase II, are specifically recruited to genes
      induced by endoplasmic reticulum (ER) stress. In good agreement with the
      recruitment of hSAGA to the ER stress-regulated genes, knockdown of hSTP20
      hampers ER stress response. Surprisingly, hSPT20 recruitment was not observed for
      genes induced by another type of stress. These results provide evidence for a
      direct and specific role of the hSPT20-containing SAGA complex in transcriptional
      induction of ER stress-responsive genes. Thus, hSAGA regulates the transcription
      of stress-responsive genes in a stress type-dependent manner.

PMID- 19114551
TI  - Metabolic dysregulation and adipose tissue fibrosis: role of collagen VI.
AB  - Adipocytes are embedded in a unique extracellular matrix whose main function is
      to provide mechanical support, in addition to participating in a variety of
      signaling events. During adipose tissue expansion, the extracellular matrix
      requires remodeling to accommodate adipocyte growth. Here, we demonstrate a
      general upregulation of several extracellular matrix components in adipose tissue
      in the diabetic state, therefore implicating "adipose tissue fibrosis" as a
      hallmark of metabolically challenged adipocytes. Collagen VI is a highly enriched
      extracellular matrix component of adipose tissue. The absence of collagen VI
      results in the uninhibited expansion of individual adipocytes and is
      paradoxically associated with substantial improvements in whole-body energy
      homeostasis, both with high-fat diet exposure and in the ob/ob background.
      Collectively, our data suggest that weakening the extracellular scaffold of
      adipocytes enables their stress-free expansion during states of positive energy
      balance, which is consequently associated with an improved inflammatory profile.
      Therefore, the disproportionate accumulation of extracellular matrix components
      in adipose tissue may not be merely an epiphenomenon of metabolically challenging
      conditions but may also directly contribute to a failure to expand adipose tissue
      mass during states of excess caloric intake.

PMID- 19114552
TI  - Stability of eukaryotic translation initiation factor 4E mRNA is regulated by
      HuR, and this activity is dysregulated in cancer.
AB  - Eukaryotic translation initiation factor 4E (eIF4E) is encoded by a potent
      oncogene which is highly elevated in many human cancers. Few studies have
      investigated how the level, and thus activity, of eIF4E is regulated in healthy
      (noncancerous) cells and how they become elevated in malignant cells. Here, our
      studies reveal a novel mechanism by which eIF4E levels are regulated at the level
      of mRNA stability. Two factors known to modulate transcript stability, HuR and
      the p42 isoform of AUF1, compete for binding to the 3' untranslated regions
      (3'UTRs) of eIF4E mRNAs. We identified a distinct AU-rich element in the 3'UTR of
      eIF4E which is responsible for HuR-mediated binding and stabilization. Our
      studies show that HuR is upregulated in malignant cancer specimens characterized
      by high eIF4E levels and that its depletion leads to reduction in eIF4E levels.
      Further, HuR and eIF4E regulate a common set of transcripts involved in cellular
      proliferation (cyclin D1 and c-myc) and neoangiogenesis (vascular endothelial
      growth factor), which suggests a functional connection between HuR and eIF4E in
      the regulation of these important processes. In summary, we present a novel model
      for the regulation of eIF4E expression and show that this model is relevant to
      elevation of eIF4E levels in malignant cells.

PMID- 19114553
TI  - Ras subcellular localization defines extracellular signal-regulated kinase 1 and
      2 substrate specificity through distinct utilization of scaffold proteins.
AB  - Subcellular localization influences the nature of Ras/extracellular signal
      regulated kinase (ERK) signals by unknown mechanisms. Herein, we demonstrate that
      the microenvironment from which Ras signals emanate determines which substrates
      will be preferentially phosphorylated by the activated ERK1/2. We show that the
      phosphorylation of epidermal growth factor receptor (EGFr) and cytosolic
      phospholipase A(2) (cPLA(2)) is most prominent when ERK1/2 are activated from
      lipid rafts, whereas RSK1 is mainly activated by Ras signals from the disordered
      membrane. We present evidence indicating that the underlying mechanism of this
      substrate selectivity is governed by the participation of different scaffold
      proteins that distinctively couple ERK1/2, activated at defined
      microlocalizations, to specific substrates. As such, we show that for cPLA(2)
      activation, ERK1/2 activated at lipid rafts interact with KSR1, whereas ERK1/2
      activated at the endoplasmic reticulum utilize Sef-1. To phosphorylate the EGFr,
      ERK1/2 activated at lipid rafts require the participation of IQGAP1. Furthermore,
      we demonstrate that scaffold usage markedly influences the biological outcome of
      Ras site-specific signals. These results disclose an unprecedented spatial
      regulation of ERK1/2 substrate specificity, dictated by the microlocalization
      from which Ras signals originate and by the selection of specific scaffold
      proteins.

PMID- 19114554
TI  - TFIIB recognition elements control the TFIIA-NC2 axis in transcriptional
      regulation.
AB  - TFIIB recognizes DNA sequence-specific motifs that can flank the TATA elements of
      the promoters of protein-encoding genes. The TFIIB recognition elements (BRE(u)
      and BRE(d)) can have positive or negative effects on transcription in a promoter
      context-dependent manner. Here we show that the BREs direct the selective
      recruitment of TFIIA and NC2 to the promoter. We find that TFIIA preferentially
      associates with BRE-containing promoters while NC2 is recruited to promoters that
      lack consensus BREs. The functional relevance of the BRE-dependent recruitment of
      TFIIA and NC2 was determined by small interfering RNA-mediated knockdown of TFIIA
      and NC2, both of which elicited BRE-dependent effects on transcription. Our
      results confirm the established functional reciprocity of TFIIA and NC2. However,
      our findings show that TFIIA assembly at BRE-containing promoters results in
      reduced transcriptional activity, while NC2 acts as a positive factor at
      promoters that lack functional BREs. Taken together, our results provide a basis
      for the selective recruitment of TFIIA and NC2 to the promoter and give new
      insights into the functional relationship between core promoter elements and
      general transcription factor activity.

PMID- 19114555
TI  - Requirement of RNA binding of mammalian eukaryotic translation initiation factor
      4GI (eIF4GI) for efficient interaction of eIF4E with the mRNA cap.
AB  - Eukaryotic mRNAs possess a 5'-terminal cap structure (cap), m(7)GpppN, which
      facilitates ribosome binding. The cap is bound by eukaryotic translation
      initiation factor 4F (eIF4F), which is composed of eIF4E, eIF4G, and eIF4A. eIF4E
      is the cap-binding subunit, eIF4A is an RNA helicase, and eIF4G is a scaffolding
      protein that bridges between the mRNA and ribosome. eIF4G contains an RNA-binding
      domain, which was suggested to stimulate eIF4E interaction with the cap in
      mammals. In Saccharomyces cerevisiae, however, such an effect was not observed.
      Here, we used recombinant proteins to reconstitute the cap binding of the
      mammalian eIF4E-eIF4GI complex to investigate the importance of the RNA-binding
      region of eIF4GI for cap interaction with eIF4E. We demonstrate that chemical
      cross-linking of eIF4E to the cap structure is dramatically enhanced by eIF4GI
      fragments possessing RNA-binding activity. Furthermore, the fusion of RNA
      recognition motif 1 (RRM1) of the La autoantigen to the N terminus of eIF4GI
      confers enhanced association between the cap structure and eIF4E. These results
      demonstrate that eIF4GI serves to anchor eIF4E to the mRNA and enhance its
      interaction with the cap structure.

PMID- 19114556
TI  - A network of hydrophobic residues impeding helix alphaC rotation maintains
      latency of kinase Gcn2, which phosphorylates the alpha subunit of translation
      initiation factor 2.
AB  - Kinase Gcn2 is activated by amino acid starvation and downregulates translation
      initiation by phosphorylating the alpha subunit of translation initiation factor
      2 (eIF2alpha). The Gcn2 kinase domain (KD) is inert and must be activated by tRNA
      binding to the adjacent regulatory domain. Previous work indicated that
      Saccharomyces cerevisiae Gcn2 latency results from inflexibility of the hinge
      connecting the N and C lobes and a partially obstructed ATP-binding site in the
      KD. Here, we provide strong evidence that a network of hydrophobic interactions
      centered on Leu-856 also promotes latency by constraining helix alphaC rotation
      in the KD in a manner relieved during amino acid starvation by tRNA binding and
      autophosphorylation of Thr-882 in the activation loop. Thus, we show that
      mutationally disrupting the hydrophobic network in various ways constitutively
      activates eIF2alpha phosphorylation in vivo and bypasses the requirement for a
      key tRNA binding motif (m2) and Thr-882 in Gcn2. In particular, replacing Leu-856
      with any nonhydrophobic residue activates Gcn2, while substitutions with various
      hydrophobic residues maintain kinase latency. We further provide strong evidence
      that parallel, back-to-back dimerization of the KD is a step on the Gcn2
      activation pathway promoted by tRNA binding and autophosphorylation. Remarkably,
      mutations that disrupt the L856 hydrophobic network or enhance hinge flexibility
      eliminate the need for the conserved salt bridge at the parallel dimer interface,
      implying that KD dimerization facilitates the reorientation of alphaC and
      remodeling of the active site for enhanced ATP binding and catalysis. We propose
      that hinge remodeling, parallel dimerization, and reorientation of alphaC are
      mutually reinforcing conformational transitions stimulated by tRNA binding and
      secured by the ensuing autophosphorylation of T882 for stable kinase activation.

PMID- 19114558
TI  - Direct link between RACK1 function and localization at the ribosome in vivo.
AB  - The receptor for activated C-kinase (RACK1), a conserved protein implicated in
      numerous signaling pathways, is a stoichiometric component of eukaryotic
      ribosomes located on the head of the 40S ribosomal subunit. To test the
      hypothesis that ribosome association is central to the function of RACK1 in vivo,
      we determined the 2.1-A crystal structure of RACK1 from Saccharomyces cerevisiae
      (Asc1p) and used it to design eight mutant versions of RACK1 to assess roles in
      ribosome binding and in vivo function. Conserved charged amino acids on one side
      of the beta-propeller structure were found to confer most of the 40S subunit
      binding affinity, whereas an adjacent conserved and structured loop had little
      effect on RACK1-ribosome association. Yeast mutations that confer moderate to
      strong defects in ribosome binding mimic some phenotypes of a RACK1 deletion
      strain, including increased sensitivity to drugs affecting cell wall biosynthesis
      and translation elongation. Furthermore, disruption of RACK1's position at the
      40S ribosomal subunit results in the failure of the mRNA binding protein Scp160
      to associate with actively translating ribosomes. These results provide the first
      direct evidence that RACK1 functions from the ribosome, implying a physical link
      between the eukaryotic ribosome and cell signaling pathways in vivo.

PMID- 19114557
TI  - An Xpb mouse model for combined xeroderma pigmentosum and cockayne syndrome
      reveals progeroid features upon further attenuation of DNA repair.
AB  - Patients carrying mutations in the XPB helicase subunit of the basal
      transcription and nucleotide excision repair (NER) factor TFIIH display the
      combined cancer and developmental-progeroid disorder xeroderma
      pigmentosum/Cockayne syndrome (XPCS). Due to the dual transcription repair role
      of XPB and the absence of animal models, the underlying molecular mechanisms of
      XPB(XPCS) are largely uncharacterized. Here we show that severe alterations in
      Xpb cause embryonic lethality and that knock-in mice closely mimicking an XPCS
      patient-derived XPB mutation recapitulate the UV sensitivity typical for XP but
      fail to show overt CS features unless the DNA repair capacity is further
      challenged by crossings to the NER-deficient Xpa background. Interestingly, the
      Xpb(XPCS) Xpa double mutants display a remarkable interanimal variance, which
      points to stochastic DNA damage accumulation as an important determinant of
      clinical diversity in NER syndromes. Furthermore, mice carrying the Xpb(XPCS)
      mutation together with a point mutation in the second TFIIH helicase Xpd are
      healthy at birth but display neonatal lethality, indicating that transcription
      efficiency is sufficient to permit embryonal development even when both TFIIH
      helicases are crippled. The double-mutant cells exhibit sensitivity to oxidative
      stress, suggesting a role for endogenous DNA damage in the onset of XPB
      associated CS.

PMID- 19114559
TI  - Evidence for a bigenic chromatin subdomain in regulation of the fetal-to-adult
      hemoglobin switch.
AB  - During development, human beta-globin locus regulation undergoes two critical
      switches, the embryonic-to-fetal and fetal-to-adult hemoglobin switches. To
      define the role of the fetal (A)gamma-globin promoter in switching, human beta
      globin-YAC transgenic mice were produced with the (A)gamma-globin promoter
      replaced by the erythroid porphobilinogen deaminase (PBGD) promoter (PBGD(A)gamma
      YAC). Activation of the stage-independent PBGD(A)gamma-globin strikingly
      stimulated native (G)gamma-globin expression at the fetal and adult stages,
      identifying a fetal gene pair or bigenic cooperative mechanism. This impaired
      fetal silencing severely suppressed both delta- and beta-globin expression in
      PBGD(A)gamma-YAC mice from fetal to neonatal stages and altered kinetics and
      delayed switching of adult beta-globin. This regulation evokes the two human
      globin switching patterns in the mouse. Both patterns of DNA demethylation and
      chromatin immunoprecipitation analysis correlated with gene activation and open
      chromatin. Locus control region (LCR) interactions detected by chromosome
      conformation capture revealed distinct spatial fetal and adult LCR bigenic
      subdomains. Since both intact fetal promoters are critical regulators of fetal
      silencing at the adult stage, we concluded that fetal genes are controlled as a
      bigenic subdomain rather than a gene-autonomous mechanism. Our study also
      provides evidence for LCR complex interaction with spatial fetal or adult bigenic
      functional subdomains as a niche for transcriptional activation and hemoglobin
      switching.

PMID- 19114560
TI  - Ikaros and GATA-1 combinatorial effect is required for silencing of human gamma
      globin genes.
AB  - During development and erythropoiesis, globin gene expression is finely modulated
      through an important network of transcription factors and chromatin modifying
      activities. In this report we provide in vivo evidence that endogenous Ikaros is
      recruited to the human beta-globin locus and targets the histone deacetylase
      HDAC1 and the chromatin remodeling protein Mi-2 to the human gamma-gene
      promoters, thereby contributing to gamma-globin gene silencing at the time of the
      gamma- to beta-globin gene transcriptional switch. We show for the first time
      that Ikaros interacts with GATA-1 and enhances the binding of the latter to
      different regulatory regions across the locus. Consistent with these results, we
      show that the combinatorial effect of Ikaros and GATA-1 impairs close proximity
      between the locus control region and the human gamma-globin genes. Since the
      absence of Ikaros also affects GATA-1 recruitment to GATA-2 promoter, we propose
      that the combinatorial effect of Ikaros and GATA-1 is not restricted to globin
      gene regulation.

PMID- 19114561
TI  - The H3K4 demethylase lid associates with and inhibits histone deacetylase Rpd3.
AB  - JmjC domain-containing proteins have been shown to possess histone demethylase
      activity. One of these proteins is the Drosophila histone H3 lysine 4 demethylase
      Little imaginal discs (Lid), which has been genetically classified as a Trithorax
      group protein. However, contrary to the supposed function of Lid in gene
      activation, the biochemical activity of this protein entails the removal of a
      histone mark that is correlated with active transcription. To understand the
      molecular mechanism behind the function of Lid, we have purified a Lid-containing
      protein complex from Drosophila embryo nuclear extracts. In addition to Lid, the
      complex contains Rpd3, CG3815/Drosophila Pf1, CG13367, and Mrg15. Rpd3 is a
      histone deacetylase, and along with Polycomb group proteins, which antagonize the
      function of Trithorax group proteins, it negatively regulates transcription. By
      reconstituting the Lid complex, we demonstrated that the demethylase activity of
      Lid is not affected by its association with other proteins. However, the
      deacetylase activity of Rpd3 is greatly diminished upon incorporation into the
      Lid complex. Thus, our finding that Lid antagonizes Rpd3 function provides an
      explanation for the genetic classification of Lid as a positive transcription
      regulator.

PMID- 19114563
TI  - Psychiatric rehabilitation: a key to prevention.

PMID- 19114564
TI  - Can we learn from history? Mental health in health care reform, revisited.
AB  - Health reform is again on the national agenda. Serious debate about how mental
      health might fit into national health policy has not occurred since 1993. The
      focus of the Clinton reformers was on benefits, integration with the general
      health system, and a new role for the public sector. A number of issues remain
      relevant today, such as uncoordinated public and private services, cost-shifting,
      and poor quality care for people with serious mental illness. This column
      considers the barriers to full inclusion of mental health in health care reform
      and proposed solutions that were identified in 1993 and describes how they can
      inform policy decisions in 2009.

PMID- 19114562
TI  - Regulation of mTORC1 and mTORC2 complex assembly by phosphatidic acid:
      competition with rapamycin.
AB  - mTOR, the mammalian target of rapamycin, is a critical node for control of cell
      growth and survival and has widely been implicated in cancer survival signals.
      mTOR exists in two complexes: mTORC1 and mTORC2. Phospholipase D (PLD) and its
      metabolite phosphatidic acid (PA) have been implicated in the regulation of mTOR;
      however, their role has been controversial. We report here that suppression of
      PLD prevents phosphorylation of the mTORC1 substrate S6 kinase (S6K) at Thr389
      and the mTORC2 substrate Akt at Ser473. Suppression of PLD also blocked insulin
      stimulated Akt phosphorylation at Ser473 and the mTORC2-dependent phosphorylation
      of PRAS40. Importantly, PA was required for the association of mTOR with Raptor
      to form mTORC1 and that of mTOR with Rictor to form mTORC2. The effect of PA was
      competitive with rapamycin-with much higher concentrations of rapamycin needed to
      compete with the PA-mTORC2 interaction than with PA-mTORC1. Suppressing PA
      production substantially increased the sensitivity of mTORC2 to rapamycin. Data
      provided here demonstrate a PA requirement for the stabilization of both mTORC1
      and mTORC2 complexes and reveal a mechanism for the inhibitory effect of
      rapamycin on mTOR. This study also suggests that by suppressing PLD activity,
      mTORC2 could be targeted therapeutically with rapamycin.

PMID- 19114565
TI  - Through a glass darkly: functional neuroimaging evidence enters the courtroom.
AB  - This column discusses problems with use of evidence based on functional brain
      scans. It describes a 2007 case in which evidence from positron emission
      tomography of the defendant's brain was used in an attempt to show that he was
      unable to have planned the sexual assault, which he did not contest committing,
      and so could not form an intent to commit the crime. Among the issues evident in
      such cases are the assumption that complex functions are localized to single
      areas of the brain and the large discrepancy between inferences that can be drawn
      from such evidence and legal standards that must be met in court.

PMID- 19114566
TI  - Washington State's initiative to disseminate and implement high-fidelity ACT
      teams.
AB  - This column describes Washington State's historic statewide initiative to
      implement ten high-fidelity assertive community treatment teams. Legislative
      support and administrative leadership facilitated the implementation of this
      evidence-based practice as part of a comprehensive transformation initiative
      within public mental health services for people with serious mental illness.
      Stakeholder feedback and initial fidelity reviews suggest that the first year has
      been successful. Crucial strategies that were important to the teams' successful
      implementation, such as training and consultation, are examined. Challenges, such
      as staff turnover, are described along with targeted approaches that have been
      integral to overcoming them. Next steps to promote sustainability and
      implications for state mental health authorities are discussed.

PMID- 19114567
TI  - Changing trends in state psychiatric hospital use from 2002 to 2005.
AB  - OBJECTIVE: National surveys have shown dramatic declines in the number of
      residents in state psychiatric hospitals since the 1950s and in the number of
      admissions since the 1970s. However, data from 2002 and 2005 indicate a reversal
      of these long-term trends. The objective of this study was to present the new
      data and to advocate for research on the factors contributing to these changes.
      METHODS: This study is based on state-level data submitted annually to the Center
      for Mental Health Services. The 11 states showing increases in admissions and
      residents between 2002 and 2005 were surveyed by telephone about the factors
      leading to the changes. RESULTS: Between 2002 and 2005, the number of admissions
      nationwide increased 21.1%, and the number of residents increased by 1.0%. State
      mental health agency staff attributed the increases principally to one factor-the
      increase in the number of forensic admissions and residents. Staff also
      identified increases in the number of admissions with schizophrenia (increased
      23.2%) and affective disorders (increased 16.3%) as a second factor, plus
      declines in the availability of housing and community-based care providers.
      CONCLUSIONS: The reversal of long-term trends may signal threats to the goal of
      community-based mental health care. Research is urgently needed to examine the
      factors associated with these increases. Potential factors to be investigated
      include the increase in the number of forensic admissions and the antecedents of
      this phenomenon, increases in the number of admissions with schizophrenia, the
      changing capacity of general hospital inpatient psychiatric services in the
      community, and changes in the demographic makeup of American society, reflected
      in an aging population and increased racial-ethnic diversity.

PMID- 19114568
TI  - Impact of substance disorders on medical expenditures for medicaid beneficiaries
      with behavioral health disorders.
AB  - OBJECTIVE: This study measured the impact of substance use disorders on Medicaid
      expenditures for behavioral and physical health care among beneficiaries with
      behavioral health disorders. METHODS: Claims for Medicaid beneficiaries with
      behavioral health diagnoses in 1999 from Arkansas, Colorado, Georgia, Indiana,
      New Jersey, and Washington were analyzed. Behavioral health and general medical
      expenditures for individuals with diagnoses of substance use disorders were
      compared with expenditures for those without such diagnoses. States were analyzed
      separately with adjustment for confounders. RESULTS: A total of 148,457
      beneficiaries met selection criteria, and 43,457 (29.3%) had a substance use
      diagnosis. Compared with other beneficiaries with behavioral health disorders,
      individuals with diagnoses of substance use disorders had significantly higher
      expenditures for physical health problems in five of six states. Approximately
      half of the additional care and expenditures were for treatment of physical
      conditions. Differences declined but remained statistically significant after
      adjustment for higher overall disease burden among beneficiaries with addictions.
      Medical expenditures for individuals with diagnoses of substance use disorders
      increased significantly with age in five of six states, whereas behavioral health
      expenditures were stable or declined. Hospital admissions for psychiatric and
      general medical reasons were higher for those with diagnoses of substance use
      disorders. CONCLUSIONS: The impact of addiction on Medicaid populations with
      behavioral health disorders is greater than the direct cost of mental health and
      addictions treatment. Higher medical expenditures can be partly attributed to
      greater prevalence of co-occurring physical disorders, but expenditures remained
      higher after adjustment for disease burden. Spending estimates based only on
      behavioral health diagnoses may significantly underestimate addictions-related
      costs, particularly for older adults.

PMID- 19114569
TI  - The quality of asthma care among adults with substance-related disorders and
      adults with mental illness.
AB  - OBJECTIVE: The purpose of this study was to investigate whether the presence of
      substance-related disorders or mental illness may affect the quality of
      medication management in asthma care. METHODS: Claims from 1999 for adult
      Medicaid patients with persistent asthma from five states were analyzed. Sample
      sizes ranged from 1,207 to 5,815. The adjusted odds of meeting two quality-of
      care measures for asthma were calculated: the Health Effectiveness Data and
      Information Set (HEDIS) measure of filling a single prescription for a controller
      medication and a non-HEDIS measure of achieving a ratio of long-term controller
      medications to total asthma medications of > or = .5. RESULTS: Odds of achieving
      the HEDIS measure were lower for patients with substance-related or schizophrenia
      disorders in two states (range of odds ratio [OR]=.69, 95% confidence interval
      [CI]=.53-.90, to OR=.81, 95% CI=.69-.96), but the odds increased for patients
      with depressive disorders in two states (OR=1.34, CI= 1.12-1.61; OR=1.37, CI=1.05
      1.77) and for patients with bipolar disorder in one state (OR=1.69, CI=1.13
      2.55). Odds of achieving the ratio measure were lower for patients with substance
      related disorders in four states (range of OR=.63, CI=.47-.88, to OR=.75, CI=.62
      .92) and higher for patients with depressive disorders, although only in one
      state (OR=1.25, CI=1.03-1.53). CONCLUSIONS: Patients with substance-related
      disorders and those with schizophrenia disorders may be receiving lower-quality
      asthma care, whereas patients with some other forms of mental illness may be
      receiving higher-quality care. Further studies are needed to identify the
      determinants of high-quality asthma care and the validity of quality measures
      based on administrative data in these populations.

PMID- 19114570
TI  - Substance use disorders as risk factors for psychiatric hospitalization in
      bipolar disorder.
AB  - OBJECTIVE: This study developed risk profiles of psychiatric hospitalization for
      veterans diagnosed as having bipolar disorder. METHODS: This study included 2,963
      veterans diagnosed as having bipolar disorder (types I, II, or not otherwise
      specified) during the 2004 fiscal year. Data were derived from the Veterans
      Affairs administrative database. Risk profiles for psychiatric hospitalization
      were generated with an iterative application of the receiver operating
      characteristic. RESULTS: In this sample 20% of the patients with bipolar disorder
      were hospitalized psychiatrically during the one-year study period. Patients
      diagnosed as having both an alcohol use disorder and polysubstance dependence and
      who also were separated from their spouse or partner had a 100% risk of
      psychiatric hospitalization; risk of psychiatric hospitalization decreased to 52%
      if the patients were not separated from their partner. Patients who were not
      diagnosed as having alcohol use disorders or polysubstance dependence and who
      were not separated from their partners exhibited the lowest risk of psychiatric
      hospitalization (12%). Among patients with a psychiatric hospitalization, 41% had
      longer lengths of stay (<14 days), with the strongest predictor of a longer
      length of stay being an age older than 77 years, which conferred a 77% risk.
      CONCLUSIONS: Alcohol use and polysubstance dependence can significantly affect
      the course of bipolar disorder, as evidenced by their associations with
      psychiatric hospitalizations. Increased focus on substance abuse among older
      adults with bipolar disorder may decrease length of psychiatric hospitalization.
      Our findings suggest that implementing substance treatment programs early in the
      course of bipolar disorder could reduce health service use.

PMID- 19114571
TI  - Mental health and substance use problems of parents involved with child welfare:
      are services offered and provided?
AB  - OBJECTIVES: This study examined service delivery to parental caregivers with
      mental health problems, substance use problems, or both. The study sought to
      determine whether, once need is identified, suitable services are offered and
      then provided. METHODS: The study was a secondary analysis of the 1994 National
      Study of Protective, Preventive, and Reunification Services Delivered to Children
      and Their Families. The national study interviewed child welfare caseworkers
      about the problems of and services provided to 2,109 families. RESULTS: Of
      parents with mental problems, 77.9% were offered services and 84.0% of those were
      provided services. Of parents with substance use problems, 65.7% were offered
      treatment and 67.5% of those were provided it. Other problems included lack of
      parenting skills, lack of education and job skills, parent-child conflict, and
      lack of income. Significant associations were found between caseworkers'
      identifying problems and offering relevant services. Caregivers with substance
      use problems were less likely to be offered substance treatment services than
      caregivers with both mental health and substance use problems. CONCLUSIONS: The
      child welfare system may facilitate service use for caregivers. More research is
      needed to understand the process of service delivery to caregivers, including why
      services are not offered to some caregivers and why some services are not
      provided after being offered. Future research should examine why caregivers with
      substance use problems are vulnerable to not receiving treatment and whether and
      how service use varies for other problems not examined in this study.

PMID- 19114572
TI  - Impact of social anxiety disorder on employment among women receiving welfare
      benefits.
AB  - OBJECTIVE: Studies in clinical and community samples have documented that social
      anxiety disorder is common, disabling, and costly. It reduces educational
      attainment and job success, and thus it may undermine economic self-sufficiency.
      The authors examined whether social anxiety disorder was an obstacle to
      successful employment in a longitudinal epidemiological study of women receiving
      welfare in an urban Michigan county. The hypothesis that social anxiety disorder
      would predict reduced work attainment was examined. METHODS: Psychiatric
      diagnoses were established with the Composite International Diagnostic Interview
      Short Form. The authors conducted a linear fixed-effects regression analysis for
      survey data with 609 respondents who completed at least the third wave of the
      Women's Employment Study in order to explore obstacles to employment among
      mothers on welfare. RESULTS: Analyses demonstrated that compared with respondents
      without social anxiety disorder, those with this disorder worked fewer months.
      The impact of social anxiety disorder was independent of and more striking than
      the effects of depression. CONCLUSIONS: By undermining efforts to obtain or
      maintain employment, social anxiety disorder poses a significant, unrecognized
      impediment to efforts to reduce welfare reliance and to help recipients achieve
      economic self-sufficiency. Because recipients may lose benefits if they fail to
      enter the workforce rapidly and if they exceed time limits for support, those
      with social anxiety disorder are at risk of extreme economic hardship. Improved
      access to effective treatments in this population could have significant public
      health and economic benefits.

PMID- 19114573
TI  - Are comparisons of consumer satisfaction with providers biased by nonresponse or
      case-mix differences?
AB  - OBJECTIVE: This study examined how consumer satisfaction ratings differ between
      mental health care providers to determine whether comparison of ratings is biased
      by differences in survey response rates or consumer characteristics. METHODS:
      Consumer satisfaction surveys mailed by a mixed-model prepaid health plan were
      examined. Survey data were linked to computerized records regarding consumers'
      demographic (age, sex, and type of insurance coverage) and clinical (primary
      diagnosis and initial versus return visit) characteristics. Statistical models
      examined probabilities of returning the survey (N=8,025 returned surveys) and of
      giving an excellent satisfaction rating. Variability was separated into within
      provider effects and between-provider effects. RESULTS: The overall response rate
      was 33.8%, and 49.9% of responders reported excellent satisfaction. Neither
      response rate nor satisfaction rating was related to primary diagnosis. Within
      the practices of individual providers, response rate and receiving an excellent
      rating were significantly associated with female sex, older age, longer
      enrollment in the health plan, and making a return visit. Analyses of between
      provider effects, however, found that only a higher proportion of return visitors
      was significantly associated with higher response rates and higher satisfaction
      ratings. CONCLUSIONS: There was little evidence that differences in response rate
      or in consumers served biased comparison of satisfaction ratings between mental
      health providers. Bias might be greater in a setting with more heterogeneous
      consumers or providers. Returning consumers gave higher ratings than first-time
      visitors, and analyses of satisfaction ratings may need to account for this
      difference. Extremely high or low ratings should be interpreted cautiously,
      especially for providers with a small number of surveys.

PMID- 19114574
TI  - Collaborative mental health care versus care as usual in a primary care setting:
      a randomized controlled trial.
AB  - OBJECTIVE: This study compared the effectiveness of treating common mental
      disorders in a collaborative care program in a primary care setting and the
      effectiveness of treating such disorders through traditional referral of patients
      to mental health services. METHODS: In a cluster randomized controlled trial, 27
      general practitioner practices in the Netherlands were designated to provide
      either collaborative care or usual care. In the collaborative care condition, a
      mental health care professional worked on site at the primary care practice and
      was available to provide patients a maximum of five appointments if they were
      referred by the general practitioner. If indicated, referral to specialized
      mental health services followed. In the usual care condition, if indicated,
      general practitioners would refer patients to off-site specialized mental health
      services. The study included 165 patients. At baseline and at three, six, and 12
      months, the study assessed patients' psychopathology, patients' quality of life,
      and patients' and general practitioners' satisfaction with the treatment
      provided. Delay in seeing a mental health provider, duration of treatment, number
      of appointments, and related treatment costs were assessed at 12 months. The data
      were analyzed with hierarchical linear models. RESULTS: Level of patients'
      psychopathology and quality of life significantly improved over time, and there
      were no significant differences between models of care. There was no significant
      difference in patients' satisfaction with care in either condition. The
      collaborative care condition resulted in significantly higher satisfaction with
      services among general practitioners, shorter referral delay, reduced time in
      treatment, fewer appointments, and consequently lower treatment costs.
      CONCLUSIONS: Collaborative care for a heterogeneous group of persons with common
      mental disorders seems to be as effective as the usual practice of referral to
      mental health services for reducing psychopathology, but it is significantly more
      efficient regarding referral delay, duration of treatment, number of
      appointments, and related treatment costs.

PMID- 19114575
TI  - An examination of the Dutch Health Care Inspectorate's supervision system for
      suicides of mental health care users.
AB  - OBJECTIVE: This study examined characteristics of suicides among mental health
      care users reported between 1996 and 2006 to the Dutch Health Care Inspectorate
      and the inspectorate's follow-up responses. The aims were to determine whether
      follow-up was associated with particular characteristics and whether the
      responses could be improved in accordance with guidelines for treatment of
      suicidal patients. METHODS: Information about patient and treatment
      characteristics was collected from a sample of 505 of the 5,483 suicide
      notifications between 1996 and 2006. The 1996-2005 sample included an equal
      number of cases to which the inspectorate did and did not respond. The 2006
      sample included the first 205 notifications in that year. RESULTS: For 2006
      notifications the response rate was 37%. The responses most frequently addressed
      how and whether the suicide was evaluated and the adequacy of treatment for the
      psychiatric disorder. A follow-up response was more likely when the suicide
      involved a young patient or a patient treated in a mental health care setting for
      less than a year or when the notification was accompanied by the mental health
      institution's plans for improving its policies. A response was less likely when
      the patient was discharged from inpatient care in the three months before the
      suicide. Since 2002 responses have more frequently emphasized the importance of
      suicide risk assessment, in accordance with guidelines. CONCLUSIONS: The
      inspectorate might improve its supervision system by placing greater emphasis on
      addressing suicidal impulses and treating older and chronically suicidal patients
      and patients soon after inpatient discharge.

PMID- 19114576
TI  - Gender differences in police encounters among persons with and without serious
      mental illness.
AB  - OBJECTIVE: This study examined the rates, patterns, and types of police contacts
      among men and women with and without serious mental illness. METHODS: Data on
      type of contact, type and number of offenses, dispositions, and repeat offenses
      were extracted from an administrative database of all police encounters in a
      midsized Canadian city over a six-year period (N=767,365). RESULTS: Men and women
      with serious mental illness represented, respectively, .5% and .4% of men and
      women who had at least one contact with the police; however, they were involved
      in 3.2% and 3.0% of all interactions, respectively. Persons with mental illness
      were more likely than those without mental illness to be in contact with police
      as suspected offenders, to have a greater number of offenses, to reoffend more
      quickly, and to be formally charged for a suspected offense. Among persons
      without mental illness in contact with police, men were much more likely than
      women to be offenders, to have a greater number of offenses, and to reoffend more
      quickly. Among persons with mental illness, however, the gender gap for these
      measures was significantly smaller. CONCLUSIONS: More resources should be
      allocated to support persons with mental illness in the community because they
      tend to have high rates of repeated police contacts for a variety of offenses.
      The findings highlight the need for gender-specific intervention programs.
      Administrative databases can be useful tools in examining police contacts among
      persons with mental illness and monitoring change after policy and program
      implementation for those at risk of police encounters.

PMID- 19114577
TI  - Conditional release in Western Australia: effect on hospital length of stay.
AB  - OBJECTIVE: The goal of this study was to determine whether the introduction of
      community treatment orders, which allow for conditional release from a
      psychiatric hospital, reduced inpatient episode durations in Western Australia by
      providing an alternative to extended inpatient stays. METHODS: The design
      compared 129 persons given community treatment orders and 117 matched control
      patients without such orders-all of whom were hospitalized during the same period
      both before and after the introduction of the community treatment order law that
      allows for conditional release. A multivariate analysis of covariance was used to
      evaluate the impact of community treatment orders on change in inpatient episode
      duration. RESULTS: The model showed a significant effect on inpatient episode
      duration (R(2)=.23, adjusted R(2)=.17, N=243, F=3.99, df=17 and 226, p<.001),
      indicating that community treatment orders (after taking all control factors into
      account) enabled a 19.16-day reduction per episode of inpatient care (t=2.13,
      df=1, p=.034) for persons given conditional release. Community-initiated
      treatment orders intended to prevent hospitalization, yet failing to do so, were
      associated with increased duration of subsequent hospitalizations (35.18 days; t=
      3.36, df=1, p<.001). CONCLUSIONS: Community treatment orders can be a useful tool
      for some but not necessarily all objectives. In the form of conditional release,
      orders reduce the likelihood of extended hospital stays. As a means to prevent
      hospitalization, the utility of community treatment orders is more complex, being
      dependent on services provided and on the judicious selection of persons for
      these orders.

PMID- 19114578
TI  - Smoking restrictions and treatment for smoking: policies and procedures in
      psychiatric inpatient units in Australia.
AB  - OBJECTIVE: Tobacco smoking is the leading preventable cause of death and disease
      in Australia. Even though smoking prevalence in the general population has been
      reduced (20% smoke), prevalence rates remain high among psychiatric inpatients
      (70%-90%). This study aimed to identify smoking policies and procedures in public
      psychiatric inpatient units in New South Wales, Australia; the provision of
      "smoking care" in such units (for example, quit-smoking advice or nicotine
      replacement therapy); and policies and procedures associated with the assessment
      of smoking status and provision of smoking care. METHODS: A cross-sectional
      survey was mailed to all public psychiatric inpatient units in New South Wales
      for completion by nurse unit managers. RESULTS: Of the 131 units, 123 units
      completed and returned surveys (94%). Over one-third (36%) of respondents
      reported instances in which inpatients began smoking during their admission. A
      similar proportion (39%) reported that staff provided cigarettes to patients who
      smoked when patients' supply was expended. Fifty percent of respondents reported
      that all patients were assessed for smoking status; however, 70% reported that
      nicotine dependence was not assessed. Units on which staff adhered to smoking
      restrictions were three times as likely to assess patients' smoking status as
      units where staff never adhered to restrictions (odds ratio=3.05, p=.01).
      CONCLUSIONS: Inadequate establishment of nonsmoking environments and of smoking
      restriction enforcement as well as inconsistencies in the provision of smoking
      care were evident. The findings suggest that failure of psychiatric services to
      provide smoking care is systemic and not related to particular types of services
      (for example acute versus nonacute or regional versus metropolitan).

PMID- 19114579
TI  - Quality improvement, pay for performance, and "outcomes measurement": what makes
      sense?
AB  - The author argues against the use of pay-for-performance programs based on broad
      based measures of patient outcomes in behavioral health care. He describes
      various problems with such programs. The purpose for collecting data is often not
      clear. Generic instruments do not measure improvement in specific mental
      disorders. Risk adjustment systems for behavioral health populations are not
      adequate. Mandated use of different instruments by payers is burdensome and
      precludes meaningful comparisons. The methodology for using outcomes-based
      approaches needs further development, and therefore the data collected will have
      little utility. The author discusses alternative approaches.

PMID- 19114580
TI  - Measuring outcomes makes good sense.

PMID- 19114582
TI  - A randomized controlled trial of a private-sector inpatient-initiated
      psychoeducation program for schizophrenia.
AB  - OBJECTIVES: Psychoeducation programs have been demonstrated to reduce relapse and
      be cost-effective for schizophrenia in academic settings, although this has not
      been examined in private care inpatient settings. METHODS: A total of 57
      consecutive patients hospitalized for an exacerbation of schizophrenia symptoms
      were randomly assigned to receive treatment as usual or Schizophrenia Treatment
      and Education Programs (STEPS), an intensive inpatient-initiated psychoeducation
      program in a private-sector treatment setting. At six months, 54% of the original
      sample was reassessed. RESULTS: Rehospitalization over six months was
      significantly less frequent among STEPS participants than among usual care
      participants (20% versus 56%, p=.038, Hedge's g effect size=.76). CONCLUSIONS:
      This controlled study demonstrated subsequent reduction of costly
      rehospitalization among patients randomly assigned to STEPS, although study
      attrition of 46% over six months may diminish the confidence in the findings.
      This is the first study to demonstrate effectiveness of inpatient-initiated
      psychoeducation in private-sector care. Larger, more comprehensive studies are
      needed to replicate these findings and identify the active components of the
      intervention yielding these apparent gains.

PMID- 19114581
TI  - Hospitalization patterns for psychiatric disorders across the lifespan in
      Australia from July 1998 to June 2005.
AB  - OBJECTIVE: This study examined specialized psychiatric hospitalization in
      Australia. METHODS: Data from July 1998 to June 2005 from the National Hospital
      Morbidity Database, which includes all public and most private hospital stays in
      Australia, were analyzed. RESULTS: Over the study period, there were 1,343,584
      psychiatric discharges (including transfers, deaths, and changes in care type).
      There was an 18.0% increase in discharges per 1,000 persons and a 20.3% reduction
      in average length of stay. The rate of discharges decreased with age, and length
      of stay increased with age. Psychiatric admission rates were higher and length of
      stay was lower for women than for men. Hospitalization rates fell with age for
      schizophrenia, manic disorders, and substance use disorders; increased with age
      for organic disorders; and peaked midlife for alcohol abuse and mood disorders. A
      late-life increase in hospitalization for depressive and personality disorders
      was observed for men. CONCLUSIONS: Planning for specialized psychiatric hospital
      services needs to take into account the mix of clinical needs by age, gender, and
      diagnosis.

PMID- 19114583
TI  - Preferred treatment for mental illness among Southwestern Nigerians.
AB  - OBJECTIVES: This study aimed to assess the southwestern Nigerian public's
      preferences for the treatment of mental illness in that region. METHODS: Adults
      (N=2,078) selected from three Nigerian communities completed questionnaires on
      sociodemographic details and on their perceptions regarding causes of,
      stereotypes of, and treatment options for mental illness. RESULTS: The preferred
      treatment option was spiritual healers, endorsed by 41% of respondents. Thirty
      percent endorsed traditional healers, and 29% endorsed hospitals and Western
      medicine. Correlates of preference for spiritual and traditional healers included
      female gender, never having provided care for persons with mental illness,
      endorsement of supernatural causation of mental illness, and lower education.
      CONCLUSIONS: The southwestern Nigerian public preferred alternatives to Western
      medicine for the treatment of mental illness. Efforts to improve professional
      mental health services in Nigeria must consider and address beliefs and
      preferences of the public in regard to mental health treatment.

PMID- 19114584
TI  - CATIE findings revisited.

PMID- 19114585
TI  - Seeking safety therapy: clarification of results.

PMID- 19114586
TI  - Health care use by victims of charcoal-burning suicide in Taiwan.

PMID- 19114587
TI  - Inactivation of soluble guanylate cyclase by stoichiometric S-nitrosation.
AB  - Dysfunction of vascular nitric oxide (NO)/cGMP signaling is believed to
      contribute essentially to various cardiovascular disorders. Besides synthesis
      and/or bioavailability of endothelial NO, impaired function of soluble guanylate
      cyclase (sGC) may play a key role in vascular dysfunction. Based on the proposal
      that desensitization of sGC through S-nitrosation contributes to vascular NO
      resistance ( Proc Natl Acad Sci U S A 104: 12312-12317, 2007 ), we exposed
      purified sGC to dinitrosyl iron complexes (DNICs), known as potent nitrosating
      agents. In the presence of 2 mM GSH, DNICs stimulated cGMP formation with EC(50)
      values of 0.1 to 0.5 microM and with an efficacy of 70 to 80% of maximal activity
      measured with 10 microM 2,2-diethyl-1-nitroso-oxyhydrazine (DEA/NO). In the
      absence of GSH, the efficacy of DNICs was markedly reduced, and sGC stimulation
      was counteracted by the inhibition of both basal and DEA/NO-stimulated cGMP
      formation at higher DNIC concentrations. Inactivation of sGC was slowly reversed
      in the presence of 2 mM GSH and associated with stoichiometric S-nitrosation of
      the protein (2.05 +/- 0.18 mol S-nitrosothiol per mol of 143-kDa heterodimer). S
      Nitrosoglutathione and sodium nitroprusside caused partial inhibition of DEA/NO
      stimulated sGC that was prevented by GSH, whereas nitroglycerin (0.3 mM) had no
      effect. Our findings indicate that nitrosation of two cysteine residues in sGC
      heterodimers results in enzyme inactivation. Protection by physiologically
      relevant concentrations of GSH (10 microM to 3 mM) suggests that S-nitrosation of
      sGC may contribute to vascular dysfunction in inflammatory disorders associated
      with nitrosative and oxidative stress and GSH depletion.

PMID- 19114588
TI  - Intestinal breast cancer resistance protein (BCRP)/Bcrp1 and multidrug resistance
      protein 3 (MRP3)/Mrp3 are involved in the pharmacokinetics of resveratrol.
AB  - The phytoestrogen resveratrol has putative health-promoting effects and is
      present in several dietary constituents. Resveratrol is metabolized extensively
      in the gut epithelium, resulting in the formation of hydrophilic glucuronic acid
      and sulfate conjugates. These polar resveratrol conjugates need specific
      transporters to cross the cell membrane. We show here that vectorial transport of
      some of these metabolites is mediated by multidrug resistance protein 3 (MRP3,
      ABCC3) and/or breast cancer resistance protein (BCRP, ABCG2) located in the
      basolateral and apical membranes of enterocytes, respectively. In vitro, MRP3
      transports resveratrol-glucuronide (Res-3-G). The absence of Mrp3 in mice results
      in altered disposition of Res-3-G and its parent compound resveratrol, leading to
      a reduced percentage of resveratrol being excreted via the urine in Mrp3(-/-)
      mice. Circumstantial evidence suggests that circulating resveratrol is formed by
      deglucuronidating Res-3-G in vivo, providing a possible explanation for the
      health beneficial effects of resveratrol in vivo, despite its rapid and extensive
      conjugation. BCRP transports Res-3-G and resveratrol sulfates in vitro, and its
      absence in mice results in high plasma levels of resveratrol-di-sulfate, a
      resveratrol metabolite hardly detectable in the plasma of wild-type mice and in
      an increased disposal of resveratrol via the urine. The profound effects of ATP
      binding cassette transporters on the disposal of resveratrol may be
      representative for the handling of several other polyphenols of dietary origin.

PMID- 19114589
TI  - Angiotensin-converting enzyme (ACE) inhibitors modulate cellular retinol-binding
      protein 1 and adiponectin expression in adipocytes via the ACE-dependent
      signaling cascade.
AB  - Inhibitors of the angiotensin-converting enzyme (ACE) decrease angiotensin II
      production and activate an intracellular signaling cascade that affects gene
      expression in endothelial cells. Because ACE inhibitors have been reported to
      delay the onset of type 2 diabetes, we determined ACE signaling-modulated gene
      expression in endothelial cells and adipocytes. Using differential gene
      expression analysis, several genes were identified that were 3-fold up- or down
      regulated by ramiprilat in cells expressing wild-type ACE versus cells expressing
      a signaling-dead ACE mutant. One up-regulated gene was the cellular retinol
      binding protein 1 (CRBP1). In adipocytes, the overexpression of CRBP1 enhanced (4
      to 5-fold) the activity of promoters containing response elements for retinol
      dependent nuclear receptors [retinoic acid receptor (RAR) and retinoid X receptor
      (RXR)] or peroxisome proliferator-activated receptors (PPAR). CRBP1
      overexpression also enhanced the promoter activity (by 470 +/- 40%) and
      expression/release of the anti-inflammatory and antiatherogenic adipokine
      adiponectin (cellular adiponectin by 196 +/- 24%, soluble adiponectin by 228 +/-
      74%). Significantly increased adiponectin secretion was also observed after ACE
      inhibitor treatment of human preadipocytes, an effect prevented by small
      interfering RNA against CRBP1. Furthermore, in ob/ob mice, ramipril markedly
      potentiated both the basal (approximately 2-fold) and rosiglitazonestimulated
      circulating levels of adiponectin. In patients with coronary artery disease or
      type 2 diabetes, ACE inhibition also significantly increased plasma adiponectin
      levels (1.6- or 2.1-fold, respectively). In summary, ACE inhibitors affect
      adipocyte homeostasis via CRBP1 through the activation of RAR/RXR-PPAR signaling
      and up-regulation of adiponectin. The latter may contribute to the beneficial
      effects of ACE inhibitors on the development of type 2 diabetes in patients with
      an activated renin-angiotensin system.

PMID- 19114590
TI  - Kai Simons: membrane master.

PMID- 19114591
TI  - Three-dimensional localization of CENP-A suggests a complex higher order
      structure of centromeric chromatin.
AB  - The histone H3 variant centromere protein A (CENP-A) is central to centromere
      formation throughout eukaryotes. A long-standing question in centromere biology
      has been the organization of CENP-A at the centromere and its implications for
      the structure of centromeric chromatin. In this study, we describe the three
      dimensional localization of CENP-A at the inner kinetochore plate through serial
      section transmission electron microscopy of human mitotic chromosomes. At the
      kinetochores of normal centromeres and at a neocentromere, CENP-A occupies a
      compact domain at the inner kinetochore plate, stretching across two thirds of
      the length of the constriction but encompassing only one third of the
      constriction width and height. Within this domain, evidence of substructure is
      apparent. Combined with previous chromatin immunoprecipitation results (Saffery,
      R., H. Sumer, S. Hassan, L.H. Wong, J.M. Craig, K. Todokoro, M. Anderson, A.
      Stafford, and K.H.A. Choo. 2003. Mol. Cell. 12:509-516; Chueh, A.C., L.H. Wong,
      N. Wong, and K.H.A. Choo. 2005. Hum. Mol. Genet. 14:85-93), our data suggest that
      centromeric chromatin is arranged in a coiled 30-nm fiber that is itself coiled
      or folded to form a higher order structure.

PMID- 19114592
TI  - The translocator maintenance protein Tam41 is required for mitochondrial
      cardiolipin biosynthesis.
AB  - The mitochondrial inner membrane contains different translocator systems for the
      import of presequence-carrying proteins and carrier proteins. The translocator
      assembly and maintenance protein 41 (Tam41/mitochondrial matrix protein 37) was
      identified as a new member of the mitochondrial protein translocator systems by
      its role in maintaining the integrity and activity of the presequence translocase
      of the inner membrane (TIM23 complex). Here we demonstrate that the assembly of
      proteins imported by the carrier translocase, TIM22 complex, is even more
      strongly affected by the lack of Tam41. Moreover, respiratory chain
      supercomplexes and the inner membrane potential are impaired by lack of Tam41.
      The phenotype of Tam41-deficient mitochondria thus resembles that of mitochondria
      lacking cardiolipin. Indeed, we found that Tam41 is required for the biosynthesis
      of the dimeric phospholipid cardiolipin. The pleiotropic effects of the
      translocator maintenance protein on preprotein import and respiratory chain can
      be attributed to its role in biosynthesis of mitochondrial cardiolipin.

PMID- 19114594
TI  - The peroxisomal membrane protein import receptor Pex3p is directly transported to
      peroxisomes by a novel Pex19p- and Pex16p-dependent pathway.
AB  - Two distinct pathways have recently been proposed for the import of peroxisomal
      membrane proteins (PMPs): a Pex19p- and Pex3p-dependent class I pathway and a
      Pex19p- and Pex3p-independent class II pathway. We show here that Pex19p plays an
      essential role as the chaperone for full-length Pex3p in the cytosol. Pex19p
      forms a soluble complex with newly synthesized Pex3p in the cytosol and directly
      translocates it to peroxisomes. Knockdown of Pex19p inhibits peroxisomal
      targeting of newly synthesized full-length Pex3p and results in failure of the
      peroxisomal localization of Pex3p. Moreover, we demonstrate that Pex16p functions
      as the Pex3p-docking site and serves as the peroxisomal membrane receptor that is
      specific to the Pex3p-Pex19p complexes. Based on these novel findings, we suggest
      a model for the import of PMPs that provides new insights into the molecular
      mechanisms underlying the biogenesis of peroxisomes and its regulation involving
      Pex3p, Pex19p, and Pex16p.

PMID- 19114593
TI  - Coordinated control of self-renewal and differentiation of neural stem cells by
      Myc and the p19ARF-p53 pathway.
AB  - The modes of proliferation and differentiation of neural stem cells (NSCs) are
      coordinately controlled during development, but the underlying mechanisms remain
      largely unknown. In this study, we show that the protooncoprotein Myc and the
      tumor suppressor p19(ARF) regulate both NSC self-renewal and their neuronal and
      glial fate in a developmental stage-dependent manner. Early-stage NSCs have low
      p19(ARF) expression and retain a high self-renewal and neurogenic capacity,
      whereas late-stage NSCs with higher p19(ARF) expression possess a lower self
      renewal capacity and predominantly generate glia. Overexpression of Myc or
      inactivation of p19(ARF) reverts the properties of late-stage NSCs to those of
      early-stage cells. Conversely, inactivation of Myc or forced p19(ARF) expression
      attenuates self-renewal and induces precocious gliogenesis through modulation of
      the responsiveness to gliogenic signals. These actions of p19(ARF) in NSCs are
      mainly mediated by p53. We propose that opposing actions of Myc and the p19(ARF)
      p53 pathway have important functions in coordinated developmental control of self
      renewal and cell fate choices in NSCs.

PMID- 19114595
TI  - The microtubule-binding protein CLIP-170 coordinates mDia1 and actin
      reorganization during CR3-mediated phagocytosis.
AB  - Microtubule dynamics are modulated by regulatory proteins that bind to their plus
      ends (+TIPs [plus end tracking proteins]), such as cytoplasmic linker protein 170
      (CLIP-170) or end-binding protein 1 (EB1). We investigated the role of +TIPs
      during phagocytosis in macrophages. Using RNA interference and dominant-negative
      approaches, we show that CLIP-170 is specifically required for efficient
      phagocytosis triggered by alphaMbeta2 integrin/complement receptor activation.
      This property is not observed for EB1 and EB3. Accordingly, whereas CLIP-170 is
      dynamically enriched at the site of phagocytosis, EB1 is not. Furthermore, we
      observe that CLIP-170 controls the recruitment of the formin mDia1, an actin
      nucleating protein, at the onset of phagocytosis and thereby controls actin
      polymerization events that are essential for phagocytosis. CLIP-170 directly
      interacts with the formin homology 2 domain of mDia1. The interaction between
      CLIP-170 and mDia1 is negatively regulated during alphaMbeta2-mediated
      phagocytosis. Our results unravel a new microtubule/actin cooperation that
      involves CLIP-170 and mDia1 and that functions downstream of alphaMbeta2
      integrins.

PMID- 19114597
TI  - Editorial: the word for this year is change.

PMID- 19114598
TI  - Deiodination and cellular proliferation: parallels between development,
      differentiation, tumorigenesis, and now regeneration.

PMID- 19114596
TI  - Proteolytic fragments of laminin promote excitotoxic neurodegeneration by up
      regulation of the KA1 subunit of the kainate receptor.
AB  - Degradation of the extracellular matrix (ECM) protein laminin contributes to
      excitotoxic cell death in the hippocampus, but the mechanism of this effect is
      unknown. To study this process, we disrupted laminin gamma1 (lamgamma1)
      expression in the hippocampus. Lamgamma1 knockout (KO) and control mice had
      similar basal expression of kainate (KA) receptors, but the lamgamma1 KO mice
      were resistant to KA-induced neuronal death. After KA injection, KA1 subunit
      levels increased in control mice but were unchanged in lamgamma1 KO mice. KA1
      levels in tissue plasminogen activator (tPA)-KO mice were also unchanged after
      KA, indicating that both tPA and laminin were necessary for KA1 up-regulation
      after KA injection. Infusion of plasmin-digested laminin-1 into the hippocampus
      of lamgamma1 or tPA KO mice restored KA1 up-regulation and KA-induced neuronal
      degeneration. Interfering with KA1 function with a specific anti-KA1 antibody
      protected against KA-induced neuronal death both in vitro and in vivo. These
      results demonstrate a novel pathway for neurodegeneration involving proteolysis
      of the ECM and KA1 KA receptor subunit up-regulation.

PMID- 19114603
TI  - Medication reconciliation in hospice: a pilot study.
AB  - BACKGROUND: The Joint Commission required implementation of medication
      reconciliation processes by January 2006. Medication reconciliation is the
      practice of acquiring an accurate medication history at each transitional point
      of care. Potential for errors increases with inaccurate medication histories.
      This study determined the extent of medication reconciliation errors in hospice.
      METHODS: Patients were enrolled from 2 hospices in Maryland (January 2007). An
      initial medication history was completed by the nurse on hospice admission. The
      pharmacist did another medication history within 5 days of admission and compared
      the medication histories. All differences were reported as medication
      discrepancies. RESULTS: There were 504 medication discrepancies. Medication
      omissions occurred most commonly. All patients had at least 1 medication
      discrepancy (average 8.7 per patient). Overall, 190 drug interactions were
      identified; most were moderately severe. CONCLUSION: Terminal patients often use
      numerous medications increasing the risk of medication errors. Accurate
      medication histories reduce errors and potential for harm.

PMID- 19114602
TI  - Baclofen as an adjuvant analgesic for cancer pain.
AB  - PURPOSE: Baclofen is a g-aminobutyric acid receptor agonist commonly used for
      managing many types of neuropathic pain. The effect of baclofen on cancer pain
      has not previously been studied. This retrospective study evaluated the efficacy
      of baclofen in patients with cancer pain. METHODS: We reviewed the medical
      records of all patients given baclofen orally as an analgesic for cancer at 5
      institutions. RESULT: Twenty-five patients received 10 to 40 mg of baclofen for
      cancer pain relief. Twenty patients have undergone neuropathic pain such as
      paroxysmal or lancing, sharp, or like an electric shock. Baclofen was effective
      in 21 of 25 patients and significantly reduced Numeric Rating Scale (pain score,
      0-10; P < .0001). Nine patients reported mild adverse events: none of these 9
      patients had to discontinue baclofen due to adverse events. CONCLUSION: Our
      findings suggest that baclofen may be a useful adjuvant analgesic in the
      treatment of cancer pain.

PMID- 19114604
TI  - End-of-life care: an interdisciplinary perspective.
AB  - The Institute of Medicine has described the "death-denying character of American
      society'' and surely, there is an opportunity to change this character. Despite
      our understandable concern with costs, end-of-life care options must be variously
      considered from economic, ethical, and legislative perspectives. We consider
      these multiple perspectives of end-of-life care in an attempt to inform current
      thinking on the part of legislators, policy makers, providers, patients,
      families/ caregivers, and insurers on the issue of end-of-life care. Society must
      be educated to understand that death can be peaceful and that end-of-life
      planning and care is an integral part of society's continuum of care. Enabling
      affordability, expanding availability, and ensuring access are the only ways of
      realizing that outcome.

PMID- 19114605
TI  - Dyspnea--a bad prognosis symptom at the end of life.
AB  - PURPOSES: Dyspnea as refractory symptom leading to sedation at the end of life
      and the place of death. Survival study in population with dyspnea. METHODS:
      Longitudinal study of terminally ill patients in a year (n = 195). We divided
      populations as (a) population with dyspnea: prevalent and incident dyspnea and
      (b) population without dyspnea. We used the statistical program Stata9 (Kaplan
      Meier and Cox logistic regression models). RESULTS: The probability of being
      sedated was 5 times higher in population with dyspnea. Dying in hospital odds
      ratio was 2.13 in patients with dyspnea. The average survival time was 52 days in
      patients with dyspnea and 69 in non-dyspnea patients. The average survival was
      similar between both groups. Patients with incident dyspnea showed a higher
      average survival than those with prevalent dyspnea. CONCLUSIONS: The connection
      between dyspnea and sedation was clearly shown. There were significant
      differences between prevalent dyspnea and incident dyspnea groups.

PMID- 19114606
TI  - Engagement of health plans and employers in addressing racial and ethnic
      disparities in health care.
AB  - Disparities in access to and quality of health care along racial and ethnic lines
      are an important national problem. Health care purchasers and payers have a
      potentially important role to play in alleviating this problem. Using national
      surveys of 609 employers and 252 health plans with HMO products in 41 U.S.
      markets, we examined awareness of racial and ethnic disparities in health care
      access and quality, perceptions of employer and health plan role in addressing
      disparities, and reported efforts to measure and reduce disparities. Our findings
      suggest that most health plans and many employers are aware of the existence of
      substantial disparities and that health plans, but not employers, have taken
      steps to examine and influence patterns of care by race and ethnicity among their
      members.

PMID- 19114607
TI  - Review of nurse home visiting interventions for community-dwelling older persons
      with existing disability.
AB  - Despite there being a considerable number of meta-analyses and reviews
      synthesizing the nurse in-home visiting literature, there have been no reviews
      examining nurse in-home visiting for patients who are already disabled. This
      article presents a literature review and synthesis of 10 trials targeted on older
      adults with disability. The review is organized into structure and process
      components related to the outcome variable disability based on the classic
      Donabedian model. The review suggests that the components of in-home visiting
      associated with favorable disability outcomes include multiple home visits,
      geriatric training and experience, health provider collaboration,
      multidimensional assessment, and theory use. In contrast, lack of process
      measures, physician collaboration, training, and specific intervention components
      targeting disability are associated with ineffective interventions. This review
      helps provide insight into variables that influence disability outcomes as well
      as the development of best-practice models of in-home visiting to older adults
      with existing disability.

PMID- 19114608
TI  - Health-related quality of life in community-dwelling older Whites and African
      Americans.
AB  - OBJECTIVE: This study assesses structural and functional characteristics of Short
      Form-36 Health Survey (SF-36) domains using community-based samples of older
      Whites and African Americans. Although the eight domains of the SF-36 have by
      convention been collapsed into two summary categories- physical health and mental
      health-the authors examine a three-factor model including physical health, mental
      health, and general well-being. They hypothesized that the general well-being
      factor would be a mediator between physical and mental health in both groups.
      METHOD: Analyses using structural equation modeling provide support for the
      approach. RESULTS: In both White and African American samples, the three-factor
      model demonstrated a better fit than the two-factor model. Also, in both groups,
      general well-being mediated the relationship between physical health and mental
      health. DISCUSSION: Findings suggest that general well-being serves as an
      intervening step between physical and mental health in both White and African
      American older adults.

PMID- 19114609
TI  - Protecting personhood and achieving quality of life for older adults with
      dementia in the U.S. health care system.
AB  - OBJECTIVE: As the numbers of persons diagnosed with Alzheimer's disease and
      related dementias increase, many questions arise pertaining to the quality of
      life of those diagnosed and the health care system as it relates to the provision
      of quality care for this population. This article examines the health disparities
      among older adults with dementia, emphasizing the protection of personhood and
      quality of life, along with a review of the barriers to health care access and
      utilization of persons living with dementia. METHOD: This literature review
      utilized electronic databases and other documents. RESULTS: The findings suggest
      that while progress has been realized toward protecting personhood and achieving
      an improved quality of life among older adults with dementia in the U.S. health
      care system challenges still exist. DISCUSSION: The implications of current and
      future public policy, avenues for further research, and strategies by which the
      health care community may better serve persons with dementia are outlined.

PMID- 19114610
TI  - Contribution of residential relocation and lifestyle to the structure of health
      trajectories.
AB  - OBJECTIVE: Underlining ecological theories of aging, we assessed the impact of
      relocation, residential type, and individual lifestyle factors on the structure
      of health status overtime. METHODS: From the data of Longitudinal Study on Aging
      II, we included older adults aged 70 and older (N = 5,294). To analyze individual
      longitudinal trajectories of health outcomes, Latent Growth Curve Modeling (LGCM)
      was employed. RESULTS: LGCMs supported that older adults' residential relocation
      and health-related lifestyles were important in preserving better health
      outcomes. Multiple structural equations corroborated the causal chains in the
      multidimensionality of health structure. DISCUSSION: These findings suggest a
      necessity to design policies for older adults to create a synergy between housing
      and health care and to translate meaningful health-related lifestyles into
      diverse long-term care settings.

PMID- 19114611
TI  - Plasma leptin levels and incidence of heart failure, cardiovascular disease, and
      total mortality in elderly individuals.
AB  - OBJECTIVE: Obesity predisposes individuals to congestive heart failure (CHF) and
      cardiovascular disease (CVD). Leptin regulates energy homeostasis, is elevated in
      obesity, and influences ventricular and vascular remodeling. We tested the
      hypothesis that leptin levels are associated with greater risk of CHF, CVD, and
      mortality in elderly individuals. RESEARCH DESIGN AND METHODS: We evaluated 818
      elderly (mean age 79 years, 62% women) Framingham Study participants attending a
      routine examination at which plasma leptin was assayed. RESULTS: Leptin levels
      were higher in women and strongly correlated with BMI (P < 0.0001). On follow-up
      (mean 8.0 years), 129 (of 775 free of CHF) participants developed CHF, 187 (of
      532 free of CVD) experienced a first CVD event, and 391 individuals died. In
      multivariable Cox regression models adjusting for established risk factors, log
      leptin was positively associated with incidence of CHF and CVD (hazard ratio [HR]
      per SD increment 1.26 [95% CI 1.03-1.55] and 1.28 [1.09-1.50], respectively).
      Additional adjustment for BMI nullified the association with CHF (0.97 [0.75
      1.24]) but only modestly attenuated the relation to CVD incidence (1.23 [1.00
      1.51], P = 0.052). We observed a nonlinear, U-shaped relation between log-leptin
      and mortality (P = 0.005 for quadratic term) with greater risk of death evident
      at both low and high leptin levels. CONCLUSIONS: In our moderate-sized community
      based elderly sample, higher circulating leptin levels were associated with a
      greater risk of CHF and CVD, but leptin did not provide incremental prognostic
      information beyond BMI. Additional investigations are warranted to elucidate the
      U-shaped relation of leptin to mortality.

PMID- 19114612
TI  - Sodium-glucose cotransport inhibition with dapagliflozin in type 2 diabetes.
AB  - OBJECTIVE: Dapagliflozin, a novel inhibitor of renal sodium-glucose cotransporter
      2, allows an insulin-independent approach to improve type 2 diabetes
      hyperglycemia. In this multiple-dose study we evaluated the safety and efficacy
      of dapagliflozin in type 2 diabetic patients. RESEARCH DESIGN AND METHODS: Type 2
      diabetic patients were randomly assigned to one of five dapagliflozin doses,
      metformin XR, or placebo for 12 weeks. The primary objective was to compare mean
      change from baseline in A1C. Other objectives included comparison of changes in
      fasting plasma glucose (FPG), weight, adverse events, and laboratory
      measurements. RESULTS: After 12 weeks, dapagliflozin induced moderate glucosuria
      (52-85 g urinary glucose/day) and demonstrated significant glycemic improvements
      versus placebo (DeltaA1C -0.55 to -0.90% and DeltaFPG -16 to -31 mg/dl). Weight
      loss change versus placebo was -1.3 to -2.0 kg. There was no change in renal
      function. Serum uric acid decreased, serum magnesium increased, serum phosphate
      increased at higher doses, and dose-related 24-h urine volume and hematocrit
      increased, all of small magnitude. Treatment-emergent adverse events were similar
      across all groups. CONCLUSIONS: Dapagliflozin improved hyperglycemia and
      facilitates weight loss in type 2 diabetic patients by inducing controlled
      glucosuria with urinary loss of approximately 200-300 kcal/day. Dapagliflozin
      treatment demonstrated no persistent, clinically significant osmolarity, volume,
      or renal status changes.

PMID- 19114613
TI  - Association among serum perfluoroalkyl chemicals, glucose homeostasis, and
      metabolic syndrome in adolescents and adults.
AB  - OBJECTIVE: Perfluoroalkyl chemicals (PFCs) have been used worldwide in a variety
      of consumer products. The effect of PFCs on glucose homeostasis is not known.
      RESEARCH DESIGN AND METHODS: We examined 474 adolescents and 969 adults with
      reliable serum measures of metabolic syndrome profile from the National Health
      and Nutrition Examination Survey 1999-2000 and 2003-2004. RESULTS: In
      adolescents, increased serum perfluorononanoic acid (PFNA) concentrations were
      associated with hyperglycemia (odds ratio [OR] 3.16 [95% CI 1.39-7.16], P <
      0.05). Increased serum PFNA concentrations also have favorable associations with
      serum HDL cholesterol (0.67 [0.45-0.99], P < 0.05). Overall, increased serum PFNA
      concentrations were inversely correlated with the prevalence of the metabolic
      syndrome (0.37 [0.21-0.64], P < 0.005). In adults, increased serum
      perfluorooctanoic acid concentrations were significantly associated with
      increased beta-cell function (beta coefficient 0.07 +/- 0.03, P < 0.05).
      Increased serum perfluorooctane sulfate (PFOS) concentrations were associated
      with increased blood insulin (0.14 +/- 0.05, P < 0.01), homeostasis model
      assessment of insulin resistance (0.14 +/- 0.05, P < 0.01), and beta-cell
      function (0.15 +/- 0.05, P < 0.01). Serum PFOS concentrations were also
      unfavorably correlated with serum HDL cholesterol (OR 1.61 [95% CI 1.15-2.26], P
      < 0.05). CONCLUSIONS: Serum PFCs were associated with glucose homeostasis and
      indicators of metabolic syndrome. Further clinical and animal studies are
      warranted to clarify putative causal relationships.

PMID- 19114614
TI  - Statin therapy is associated with lower total but not bioavailable or free
      testosterone in men with type 2 diabetes.
AB  - OBJECTIVE: There is a high prevalence of hypogonadism in men with type 2
      diabetes. This will lead to an increase in assessments of hypogonadism. Statins
      could potentially decrease testosterone levels by reducing the availability of
      cholesterol for androgen synthesis. We compared testosterone levels and
      hypogonadal symptoms with statin use in a cross-sectional study of 355 men with
      type 2 diabetes. RESEARCH DESIGN AND METHODS: Total testosterone, sex hormone
      binding globulin (SHBG), and estradiol were measured by an enzyme-linked
      immunosorbent assay. Bioavailable testosterone was measured by the modified
      ammonium sulfate precipitation method. Free testosterone was calculated using
      Vermeulen's formula. Symptoms of hypogonadism were assessed using the Androgen
      Deficiency in the Aging Male questionnaire. RESULTS: Statins were associated with
      lower total testosterone (11.9 vs. 13.4 nmol/l, P = 0.006) and a trend toward
      lower SHBG (29.4 vs. 35.3 nmol/l, P = 0.034) compared with no treatment.
      Bioavailable testosterone, free testosterone, estradiol, and hypogonadal symptoms
      were not affected. Subanalysis showed that atorvastatin was associated with
      reduced total testosterone (11.4 vs. 13.4 nmol/l, P = 0.006) and a trend toward
      reduced SHBG (27.6 vs. 35.3 nmol/l, P = 0.022) compared with no treatment, and
      there was an apparent dose-response effect with the lowest levels of total
      testosterone seen in men treated with >or=20 mg atorvastatin (9.6 nmol/l, P =
      0.017). Simvastatin use was not associated with significant reductions in
      testosterone or SHBG levels. CONCLUSIONS: Assessing androgen status using total
      testosterone in men with type 2 diabetes treated with statins, particularly
      atorvastatin, may potentially lead to diagnostic error. Levels of bioavailable
      testosterone or free testosterone are recommended for the assessment of
      hypogonadism in this group if total testosterone levels are borderline.

PMID- 19114615
TI  - Performance of the UK Prospective Diabetes Study Risk Engine and the Framingham
      Risk Equations in Estimating Cardiovascular Disease in the EPIC- Norfolk Cohort.
AB  - OBJECTIVE: The purpose of this study was to examine the performance of the UK
      Prospective Diabetes Study (UKPDS) Risk Engine (version 3) and the Framingham
      risk equations (2008) in estimating cardiovascular disease (CVD) incidence in
      three populations: 1) individuals with known diabetes; 2) individuals with
      nondiabetic hyperglycemia, defined as A1C >or=6.0%; and 3) individuals with
      normoglycemia defined as A1C <6.0%. RESEARCH DESIGN AND METHODS: This was a
      population-based prospective cohort (European Prospective Investigation of Cancer
      Norfolk). Participants aged 40-79 years recruited from U.K. general practices
      attended a health examination (1993-1998) and were followed for CVD events/death
      until April 2007. CVD risk estimates were calculated for 10,137 individuals.
      RESULTS: Over 10.1 years, there were 69 CVD events in the diabetes group (25.4%),
      160 in the hyperglycemia group (17.7%), and 732 in the normoglycemia group
      (8.2%). Estimated CVD 10-year risk in the diabetes group was 33 and 37% using the
      UKPDS and Framingham equations, respectively. In the hyperglycemia group,
      estimated CVD risks were 31 and 22%, respectively, and for the normoglycemia
      group risks were 20 and 14%, respectively. There were no significant differences
      in the ability of the risk equations to discriminate between individuals at
      different risk of CVD events in each subgroup; both equations overestimated CVD
      risk. The Framingham equations performed better in the hyperglycemia and
      normoglycemia groups as they did not overestimate risk as much as the UKPDS Risk
      Engine, and they classified more participants correctly. CONCLUSIONS: Both the
      UKPDS Risk Engine and Framingham risk equations were moderately effective at
      ranking individuals and are therefore suitable for resource prioritization.
      However, both overestimated true risk, which is important when one is using
      scores to communicate prognostic information to individuals.

PMID- 19114616
TI  - Circulating retinol-binding protein 4 and subclinical cardiovascular disease in
      the elderly.
AB  - OBJECTIVE: We evaluated associations of serum retinol-binding protein 4 (RBP4)
      with subclinical cardiovascular disease (CVD). RESEARCH DESIGN AND METHODS:
      Subclinical CVD was measured with echocardiography, carotid artery ultrasound,
      brachial artery ultrasound, and invasive forearm endothelial vasoreactivity in
      1,008 70-year-old participants (50% women) of the Prospective Investigation of
      the Vasculature in Uppsala Seniors (PIVUS) study. RESULTS: In analyses adjusted
      for multiple CVD risk factors, we observed inverse associations of RBP4 with
      carotid artery intima-media (beta -0.39, 95% CI -0.55 to -0.22) and plaque (beta 
      0.33, 95% CI -0.60 to -0.05) echogenicity (gray scale median). CONCLUSIONS:
      Circulating RBP4 concentrations were inversely associated with intima-media and
      plaque echogenicity in carotid arteries. These findings imply that RBP4 could be
      involved in the development of atherosclerosis.

PMID- 19114617
TI  - Progression to impaired glucose regulation and diabetes in the population-based
      Inter99 study.
AB  - OBJECTIVE: The purpose of this study was to estimate the progression rates to
      impaired glucose regulation (impaired fasting glucose or impaired glucose
      tolerance) and diabetes in the Danish population-based Inter99 study and in a
      high-risk subpopulation, separately. RESEARCH DESIGN AND METHODS: From a
      population-based primary prevention study, the Inter99 study, 4,615 individuals
      without diabetes at baseline and with relevant follow-up data were divided into a
      low- and a high-risk group based on a risk estimate of ischemic heart disease or
      the presence of risk factors (smoking, hypertension, hypercholesterolemia,
      obesity, or impaired glucose tolerance). High-risk individuals (57.1%) were
      examined with an oral glucose tolerance test at 1 and 3 years, and all of the
      participants were reexamined at the 5-year follow-up. Person-years at risk were
      calculated. Progression rates to impaired glucose regulation and diabetes were
      estimated directly from baseline to the 5-year follow-up for all the participants
      and from baseline through the 1- and 3- to 5-year follow-up examinations for the
      high-risk individuals, separately. RESULTS: In the combined low- and high-risk
      group, 2.1 individuals per 100 person-years progressed from normal glucose
      tolerance (NGT) to impaired glucose regulation or diabetes. Among high-risk
      individuals, 5.8 per 100 person-years with NGT progressed to impaired glucose
      regulation or diabetes, and 4.9 per 100 person-years progressed from impaired
      glucose regulation to diabetes. CONCLUSIONS: Progression rates to impaired
      glucose regulation using the current World Health Organization classification
      criteria were calculated for the first time in a large European population-based
      study. The progression rates to diabetes show the same pattern as seen in the few
      similar European studies.

PMID- 19114618
TI  - Type 1 diabetes and hypoglycemia.

PMID- 19114619
TI  - Translating the A1C assay into estimated average glucose values: response to
      Nathan et al.

PMID- 19114620
TI  - Translating the A1C assay into estimated average glucose values: response to
      Nathan et al.

PMID- 19114622
TI  - Osteoprotegerin levels in women with prior gestational diabetes mellitus.

PMID- 19114623
TI  - Serum visceral adipose tissue-derived serine protease inhibitor concentrations in
      human obesity and polycystic ovary syndrome.

PMID- 19114624
TI  - Passing the baton.

PMID- 19114625
TI  - Difficulties in the use of risk factors to screen for gestational diabetes
      mellitus.

PMID- 19114626
TI  - Long-standing sulfonylurea therapy after pubertal relapse of neonatal diabetes in
      a case of uniparental paternal isodisomy of chromosome 6.

PMID- 19114627
TI  - Prevalence and control of diabetes and impaired fasting glucose in New York City.
AB  - OBJECTIVE: To determine the prevalence of diabetes and impaired fasting glucose
      (IFG) and to assess clinical management indicators among adults with diabetes in
      a representative sample of New York City adults. RESEARCH DESIGN AND METHODS: In
      2004, New York City implemented the first community-level Health and Nutrition
      Examination Survey (NYC HANES), modeled after the National Health and Nutrition
      Examination Survey (NHANES). We used an interview to determine previously
      diagnosed diabetes and measured fasting plasma glucose to determine undiagnosed
      diabetes and IFG in a probability sample of 1,336 New York City adults. We
      assessed glycemic control and other clinical indicators using standardized NHANES
      protocols. RESULTS: The prevalence of diabetes among New York City adults was
      12.5% (95% CI 10.3-15.1): 8.7% diagnosed and 3.8% undiagnosed. Nearly one-fourth
      (23.5%) of adults had IFG. Asians had the highest prevalence of impaired glucose
      metabolism (diabetes 16.1%, IFG 32.4%) but were significantly less likely to be
      obese. Among adults with diagnosed diabetes, less than one-half (45%) had A1C
      levels <7%; one-half (50%) had elevated blood pressure measures at interview, 43%
      of whom were not on antihypertensive medications; nearly two-thirds (66%) had
      elevated LDL levels, and only 10% had their glucose, blood pressure, and
      cholesterol all at or below recommended levels. Most adults (84%) with diagnosed
      diabetes were on medication, but only 12% were receiving insulin. CONCLUSIONS: In
      New York City, diabetes and IFG are widespread. Policies and structural
      interventions to promote physical activity and healthy eating should be
      prioritized. Improved disease management systems are needed for people with
      diabetes.

PMID- 19114628
TI  - New York City Health and Nutrition Examination Survey: a model for urban health
      surveillance.

PMID- 19114629
TI  - ADA research funding in 2009: where will we be?

PMID- 19114630
TI  - Functional or fantasy? Examining the implications of subjective temporal
      perspective "trajectories" for life satisfaction.
AB  - In a 5-year longitudinal study of young community adults, the authors examined
      subjective temporal perspective (STP) "trajectories" derived from ratings of
      past, present, and anticipated future life satisfaction (LS) collected at two
      time points. Upward STP trajectories (past < present < future LS) were normative
      at both time points. Opposing hypotheses were derived from the literature
      concerning the potential positive versus negative implications of upward STP
      trajectories. Using latent trajectory modeling, individual differences in STP
      trajectories were examined in relation to mental, physical, and interpersonal
      functioning as well as future satisfaction bias (over- vs. underestimation of
      future LS). Steeper upward STP trajectories were associated with less positive
      functioning, both concurrently and prospectively, as well as greater future
      satisfaction bias. Therefore, rather than representing a realistic, adaptive form
      of self-enhancement, steep upward STP trajectories for LS appeared to be a form
      of fantasizing and wishful thinking, associated with distress, dissatisfaction,
      and dysfunction.

PMID- 19114631
TI  - Race as a moderator of the relationship between religiosity and political
      alignment.
AB  - Religiosity, especially religious fundamentalism, is often assumed to have an
      inherent connection with conservative politics. This article proposes that the
      relationship varies by race in the United States. In Study 1, race moderated the
      relationships between religiosity indicators and political alignment in a
      nationally representative sample. In Study 2, the effect replicated in a student
      sample with more reliable measures. Among both Black and Latino Americans, the
      relationship between religiosity and conservative politics is far weaker than it
      is among White Americans, and it is sometimes altogether absent. In Study 3, a
      tradition-focused view of religion was found to more strongly mediate the link
      between religiosity and political attitudes among Whites than it did among Blacks
      and Latinos. It is argued that the relationship between religiosity and political
      alignment is best understood as a product of cultural-historical conditions
      associated with group memberships.

PMID- 19114634
TI  - Regulated RNA editing and functional epistasis in Shaker potassium channels.
AB  - Regulated point modification by an RNA editing enzyme occurs at four conserved
      sites in the Drosophila Shaker potassium channel. Single mRNA molecules can
      potentially represent any of 2(4) = 16 permutations (isoforms) of these natural
      variants. We generated isoform expression profiles to assess sexually dimorphic,
      spatial, and temporal differences. Striking tissue-specific expression was seen
      for particular isoforms. Moreover, isoform distributions showed evidence for
      coupling (linkage) of editing sites. Genetic manipulations of editing enzyme
      activity demonstrated that a chief determinant of Shaker editing site choice
      resides not in the editing enzyme, but rather, in unknown factors intrinsic to
      cells. Characterizing the biophysical properties of currents in nine isoforms
      revealed an unprecedented feature, functional epistasis; biophysical phenotypes
      of isoforms cannot be explained simply by the consequences of individual editing
      effects at the four sites. Our results unmask allosteric communication across
      disparate regions of the channel protein and between evolved and regulated amino
      acid changes introduced by RNA editing.

PMID- 19114635
TI  - Mutations at the signature sequence of CFTR create a Cd(2+)-gated chloride
      channel.
AB  - The canonical sequence LSGGQ, also known as the signature sequence, defines the
      adenosine triphosphate (ATP)-binding cassette transporter superfamily.
      Crystallographic studies reveal that the signature sequence, together with the
      Walker A and Walker B motifs, forms the ATP-binding pocket upon dimerization of
      the two nucleotide-binding domains (NBDs) in a head-to-tail configuration. The
      importance of the signature sequence is attested by the fact that a glycine to
      aspartate mutation (i.e., G551D) in cystic fibrosis transmembrane conductance
      regulator (CFTR) results in a severe phenotype of cystic fibrosis. We previously
      showed that the G551D mutation completely eliminates ATP-dependent gating of the
      CFTR chloride channel. Here, we report that micromolar [Cd(2+)] can dramatically
      increase the activity of G551D-CFTR in the absence of ATP. This effect of Cd(2+)
      is not seen in wild-type channels or in G551A. Pretreatment of G551D-CFTR with
      the cysteine modification reagent 2-aminoethyl methane thiosulfonate hydrobromide
      protects the channel from Cd(2+) activation, suggesting an involvement of
      endogenous cysteine residue(s) in mediating this effect of Cd(2+). The mutants
      G551C, L548C, and S549C, all in the signature sequence of CFTR's NBD1, show
      robust response to Cd(2+). On the other hand, negligible effects of Cd(2+) were
      seen with T547C, Q552C, and R553C, indicating that a specific region of the
      signature sequence is involved in transmitting the signal of Cd(2+) binding to
      the gate. Collectively, these results suggest that the effect of Cd(2+) is
      mediated by a metal bridge formation between yet to be identified cysteine
      residue(s) and the engineered aspartate or cysteine in the signature sequence. We
      propose that the signature sequence serves as a switch that transduces the signal
      of ligand binding to the channel gate.

PMID- 19114636
TI  - The skeletal L-type Ca(2+) current is a major contributor to excitation-coupled
      Ca(2+) entry.
AB  - The term excitation-coupled Ca(2+) entry (ECCE) designates the entry of
      extracellular Ca(2+) into skeletal muscle cells, which occurs in response to
      prolonged depolarization or pulse trains and depends on the presence of both the
      1,4-dihydropyridine receptor (DHPR) in the plasma membrane and the type 1
      ryanodine receptor in the sarcoplasmic reticulum (SR) membrane. The ECCE pathway
      is blocked by pharmacological agents that also block store-operated Ca(2+) entry,
      is inhibited by dantrolene, is relatively insensitive to the DHP antagonist
      nifedipine (1 microM), and is permeable to Mn(2+). Here, we have examined the
      effects of these agents on the L-type Ca(2+) current conducted via the DHPR. We
      found that the nonspecific cation channel antagonists (2-APB, SKF 96356, La(3+),
      and Gd(3+)) and dantrolene all inhibited the L-type Ca(2+) current. In addition,
      complete (>97%) block of the L-type current required concentrations of nifedipine
      >10 microM. Like ECCE, the L-type Ca(2+) channel displays permeability to Mn(2+)
      in the absence of external Ca(2+) and produces a Ca(2+) current that persists
      during prolonged ( approximately 10-second) depolarization. This current appears
      to contribute to the Ca(2+) transient observed during prolonged KCl
      depolarization of intact myotubes because (1) the transients in normal myotubes
      decayed more rapidly in the absence of external Ca(2+); (2) the transients in
      dysgenic myotubes expressing SkEIIIK (a DHPR alpha(1S) pore mutant thought to
      conduct only monovalent cations) had a time course like that of normal myotubes
      in Ca(2+)-free solution and were unaffected by Ca(2+) removal; and (3) after
      block of SR Ca(2+) release by 200 microM ryanodine, normal myotubes still
      displayed a large Ca(2+) transient, whereas no transient was detectable in
      SkEIIIK-expressing dysgenic myotubes. Collectively, these results indicate that
      the skeletal muscle L-type channel is a major contributor to the Ca(2+) entry
      attributed to ECCE.

PMID- 19114637
TI  - Voltage- and [ATP]-dependent gating of the P2X(2) ATP receptor channel.
AB  - P2X receptors are ligand-gated cation channels activated by extracellular
      adenosine triphosphate (ATP). Nonetheless, P2X(2) channel currents observed
      during the steady-state after ATP application are known to exhibit voltage
      dependence; there is a gradual increase in the inward current upon
      hyperpolarization. We used a Xenopus oocyte expression system and two-electrode
      voltage clamp to analyze this "activation" phase quantitatively. We characterized
      the conductance-voltage relationship in the presence of various [ATP], and
      observed that it shifted toward more depolarized potentials with increases in
      [ATP]. By analyzing the rate constants for the channel's transition between a
      closed and an open state, we showed that the gating of P2X(2) is determined in a
      complex way that involves both membrane voltage and ATP binding. The activation
      phase was similarly recorded in HEK293 cells expressing P2X(2) even by inside-out
      patch clamp after intensive perfusion, excluding a possibility that the gating is
      due to block/unblock by endogenous blocker(s) of oocytes. We investigated its
      structural basis by substituting a glycine residue (G344) in the second
      transmembrane (TM) helix, which may provide a kink that could mediate "gating."
      We found that, instead of a gradual increase, the inward current through the
      G344A mutant increased instantaneously upon hyperpolarization, whereas a G344P
      mutant retained an activation phase that was slower than the wild type (WT).
      Using glycine-scanning mutagenesis in the background of G344A, we could recover
      the activation phase by introducing a glycine residue into the middle of second
      TM. These results demonstrate that the flexibility of G344 contributes to the
      voltage-dependent gating. Finally, we assumed a three-state model consisting of a
      fast ATP-binding step and a following gating step and estimated the rate
      constants for the latter in P2X(2)-WT. We then executed simulation analyses using
      the calculated rate constants and successfully reproduced the results observed
      experimentally, voltage-dependent activation that is accelerated by increases in
      [ATP].

PMID- 19114639
TI  - Expression of concern.

PMID- 19114638
TI  - Molecular basis for cation selectivity in claudin-2-based paracellular pores:
      identification of an electrostatic interaction site.
AB  - Paracellular ion transport in epithelia is mediated by pores formed by members of
      the claudin family. The degree of selectivity and the molecular mechanism of ion
      permeation through claudin pores are poorly understood. By expressing a high
      conductance claudin isoform, claudin-2, in high-resistance Madin-Darby canine
      kidney cells under the control of an inducible promoter, we were able to
      quantitate claudin pore permeability. Claudin-2 pores were found to be narrow,
      fluid filled, and cation selective. Charge selectivity was mediated by the
      electrostatic interaction of partially dehydrated permeating cations with a
      negatively charged site within the pore that is formed by the side chain carboxyl
      group of aspartate-65. Thus, paracellular pores use intrapore electrostatic
      binding sites to achieve a high conductance with a high degree of charge
      selectivity.

PMID- 19114640
TI  - Protective role of angiotensin II subtype 2 receptor in blood pressure increase
      in obese Zucker rats.
AB  - Earlier, we reported that there was an increase in angiotensin II type 2 (AT(2))
      receptor expression in the renal proximal tubule, and selective activation of the
      AT(2) receptor by AT(2) agonist inhibits Na,K-ATPase activity in the proximal
      tubules and increases urinary Na excretion in obese Zucker rats. We hypothesized
      that the AT(2) receptor has a protective role against blood pressure increase in
      obese Zucker rats. To test this hypothesis, we treated obese Zucker rats with the
      AT(2) receptor antagonist PD123319 (PD; 30 microg/kg per minute) using osmotic
      pumps. Age-matched lean rats and vehicle-treated obese Zucker rats served as
      controls. On day 15 of the treatment with PD, arterial blood pressure was
      measured by cannulation of the left carotid artery under anesthesia. Control
      obese rats exhibited higher mean arterial pressure (122.0+/-3.4 mm Hg) compared
      with lean control rats (97.0+/-4.8 mm Hg). The PD treatment of obese rats raised
      mean arterial pressure further by 13 mm Hg. The plasma renin activity was
      significantly increased in the PD-treated obese compared with control-obese or
      lean rats. Western blot analysis revealed that the PD treatment in obese rats
      caused an approximately 3-fold increase in the renin expression in the kidney
      cortex but had no effect on the expression of the cortical angiotensin II type 1
      and AT(2) receptors. The present study suggests that the renal AT(2) receptors
      provide a protective role against blood pressure increase in obese Zucker rats,
      and this protective effect, in part, could be because of the ability of the AT(2)
      receptors to keep the kidney renin expression low in obese rats.

PMID- 19114641
TI  - Mitochondrial dysfunction and mitochondrial-produced reactive oxygen species: new
      targets for neurogenic hypertension?

PMID- 19114642
TI  - Sleep modulates hypertension in leptin-deficient obese mice.
AB  - Leptin increases sympathetic activity, possibly contributing to hypertension in
      obese subjects. Hypertension increases cardiovascular mortality, with nighttime
      (sleep) blood pressure having a substantial prognostic value. We measured blood
      pressure in male leptin-deficient obese mice (ob/ob; n=7) and their lean wild
      type littermates (+/+; n=11) during wakefulness, non-rapid-eye-movement sleep,
      and rapid-eye-movement sleep to investigate whether, in the absence of leptin,
      derangements of blood pressure are still associated with obesity and depend on
      the wake-sleep state. Mice were implanted with a telemetric pressure transducer
      and electrodes for discriminating wake-sleep states. Mean blood pressure was
      significantly higher in ob/ob than in +/+ mice during wakefulness (7.3+/-2.6 mm
      Hg) and non-rapid-eye-movement sleep (6.7+/-2.8 mm Hg) but not during rapid-eye
      movement sleep (2.6+/-2.6 mm Hg). In ob/ob and +/+ mice, mean blood pressure was
      substantially higher during wakefulness than during non-rapid-eye-movement sleep.
      On passing from non-rapid-eye-movement sleep to rapid-eye-movement sleep, mean
      blood pressure decreased significantly in ob/ob but not in +/+ mice. The time
      spent during wakefulness was lower in ob/ob than in +/+ mice during the dark
      (active) period, whereas the opposite occurred during the light (rest) period.
      Consequently, mean blood pressure was significantly higher in ob/ob than in +/+
      mice during the light (8.2+/-2.4 mm Hg) but not during the dark (3.0+/-2.9 mm Hg)
      period. These data suggest that, in the absence of leptin, obesity may entail
      hypertensive derangements of blood pressure, which are substantially modulated by
      the cardiovascular effects of the wake-sleep states.

PMID- 19114644
TI  - A virtuous cycle to improve hypertension outcomes at a national level: linking
      public health and individualized medicine.

PMID- 19114643
TI  - Mineralocorticoid receptor antagonism attenuates vascular apoptosis and injury
      via rescuing protein kinase B activation.
AB  - Emerging evidence indicates that mineralocorticoid receptor (MR) blockade reduces
      the risk of cardiovascular events beyond those predicted by its blood pressure
      lowering actions; however, the underlying mechanisms remain unclear. To
      investigate whether protection elicited by MR blockade is through attenuation of
      vascular apoptosis and injury, independently of blood pressure lowering, we
      administered a low dose of the MR antagonist spironolactone or vehicle for 21
      days to hypertensive transgenic Ren2 rats with elevated plasma aldosterone
      levels. Although Ren2 rats developed higher systolic blood pressures compared
      with Sprague-Dawley littermates, low-dose spironolactone treatment did not reduce
      systolic blood pressure compared with untreated Ren2 rats. Ren2 rats exhibited
      vascular injury as evidenced by increased apoptosis, hemidesmosome-like structure
      loss, mitochondrial abnormalities, and lipid accumulation compared with Sprague
      Dawley rats, and these abnormalities were attenuated by MR antagonism. Protein
      kinase B activation is critical to vascular homeostasis via regulation of cell
      survival and expression of apoptotic genes. Protein kinase B serine(473)
      phosphorylation was impaired in Ren2 aortas and restored with MR antagonism. In
      vivo MR antagonist treatment promoted antiapoptotic effects by increasing
      phosphorylation of BAD serine(136) and expression of Bcl-2 and Bcl-xL, decreasing
      cytochrome c release and BAD expression, and suppressing caspase-3 activation.
      Furthermore, MR antagonism substantially reduced the elevated NADPH oxidase
      activity and lipid peroxidation, expression of angiotensin II, angiotensin type 1
      receptor, and MR in Ren2 vasculature. These results demonstrate that MR
      antagonism protects the vasculature from aldosterone-induced vascular apoptosis
      and structural injury via rescuing protein kinase B activation, independent of
      blood pressure effects.

PMID- 19114646
TI  - Increases in antihypertensive prescriptions and reductions in cardiovascular
      events in Canada.
AB  - The Canadian Hypertension Education Program, an extensive professional education
      program to improve the management of hypertension, was started in 1999. There
      were very large increases in diagnosis and treatment of hypertension in the first
      4 years after initiation of the program. The purpose of this study was to examine
      the association between the changes in antihypertensive therapy with changes in
      hospitalization and death from major hypertension-related cardiovascular diseases
      in Canada between 1992 and 2003. Using various national databases, Canadian
      standardized yearly mortality and hospitalization rates per 1000 for stroke,
      heart failure, and acute myocardial infarction were calculated for individuals
      aged >or=20 years and regressed against antihypertensive prescription rates.
      Changes in rates were examined in a time series analysis. There were significant
      reductions (P<0.0001) in the rate of death from stroke, heart failure, and
      myocardial infarction starting in 1999. There was also a reduction in
      hospitalization rate from stroke (P<0.0001) and heart failure (P<0.0001) but not
      myocardial infarction in 1999. The changes in death (P<0.001 for all 3 diseases)
      and hospitalization (P<0.0001 for stroke and heart failure; P=0.018 for acute
      myocardial infarction) were associated with the increases in antihypertensive
      prescriptions. This study demonstrates that the reduction in cardiovascular death
      and hospitalization rates is associated with an increase in antihypertensive
      prescriptions and that it coincides with the introduction of the Canadian
      Hypertension Education Program. The Canadian Hypertension Education Program
      educational model for improving health care could be adopted by other countries
      with well-developed professional and scientific societies.

PMID- 19114645
TI  - Arthur C. Corcoran Memorial Lecture. Sympathetic activity, vascular capacitance,
      and long-term regulation of arterial pressure.

PMID- 19114647
TI  - Transient receptor potential vanilloid gene deletion exacerbates inflammation and
      atypical cardiac remodeling after myocardial infarction.
AB  - The transient receptor potential vanilloid (TRPV1) channels expressed in sensory
      afferent fibers innervating the heart may be activated by protons or
      endovanilloids released during myocardial ischemia (MI), leading to angina.
      Although our previous in vitro data indicate that TRPV1 activation may preserve
      cardiac function after ischemia-reperfusion injury, the underlying mechanisms are
      largely unknown. To test the hypothesis that TRPV1 modulates inflammatory and
      early remodeling processes to prevent cardiac functional deterioration after
      myocardial infarction, TRPV1-null mutant (TRPV1(-/-)) and wild-type (WT) mice
      were subjected to left anterior descending coronary ligation or sham operation.
      The infarct size was greater in TRPV1(-/-) than in WT mice (P<0.001) 3 days after
      MI, and the mortality rate was higher in TRPV1(-/-) than in WT mice (P<0.05) 7
      days after MI. The levels of plasma cardiac troponin I; cytokines, including
      tumor necrosis factor-alpha, interleukin-1beta, and interleukin-6; chemokines,
      including monocyte chemoattractant protein-1 and macrophage inflammatory protein
      2; and infiltration of inflammatory cells, including neutrophils, macrophages,
      and myofibroblasts; as well as collagen contents, were greater in TRPV1(-/-) than
      in WT mice (P<0.05) in the infarct area on days 3 and 7 after MI. Changes in left
      ventricular geometry led to increased end-systolic and -diastolic diameters and
      reduced contractile function in TRPV1(-/-) compared with WT mice. These data show
      that TRPV1 gene deletion results in excessive inflammation, disproportional left
      ventricular remodeling, and deteriorated cardiac function after MI, indicating
      that TRPV1 may prevent infarct expansion and cardiac injury by inhibiting
      inflammation and abnormal tissue remodeling.

PMID- 19114648
TI  - Oxidative impairment of mitochondrial electron transport chain complexes in
      rostral ventrolateral medulla contributes to neurogenic hypertension.
AB  - The role for mitochondrial electron transport chain (ETC) in neurogenic
      hypertension is unidentified. We evaluated the hypothesis that feedforward
      depression of mitochondrial ETC functions by superoxide anion (O(2)(.-)) and
      hydrogen peroxide (H(2)O(2)) in rostral ventrolateral medulla (RVLM), a brain
      stem site that maintains sympathetic vasomotor tone and contributes to oxidative
      stress and neural mechanism of hypertension. Compared with normotensive Wistar
      Kyoto rats, spontaneously hypertensive rats exhibited mitochondrial ETC
      dysfunctions in RVLM in the forms of depressed complex I or III activity and
      reduced electron coupling capacity between complexes I and III or II and III.
      Microinjection of coenzyme Q(10) into RVLM of spontaneously hypertensive rats
      reversed the depressed ETC activity and augmented O(2)(.-) production and
      hypertensive phenotypes. This mobile electron carrier also antagonized the
      elevated H(2)O(2) in RVLM and vasopressor responses to complex I (rotenone) or
      III (antimycin A) inhibitor in Wistar-Kyoto or prehypertensive rats.
      Intracerebroventricular infusion of angiotensin II promoted mitochondrial ETC
      dysfunctions in Wistar-Kyoto rats, and coenzyme Q(10) or gene knockdown of the
      p22(phox) subunit of NADPH oxidase antagonized the resultant elevation of
      H(2)O(2) in RVLM. Overexpression of superoxide dismutase or catalase in RVLM of
      spontaneously hypertensive rats by gene transfer reversed mitochondrial
      dysfunctions and blunted the augmented O(2)(.-) and H(2)O(2) in RVLM. We conclude
      that O(2)(.-)- and H(2)O(2)-dependent feedforward impairment of mitochondrial ETC
      complexes because of predisposed downregulation of superoxide dismutase or
      catalase and a cross-talk between NADPH oxidase-derived O(2)(.-) and ETC enzymes
      contribute to chronic oxidative stress in the RVLM of spontaneously hypertensive
      rats, leading to augmented sympathetic vasomotor tone and hypertension.

PMID- 19114649
TI  - Evaluation of new generation Salmonella enterica serovar Typhimurium vaccines
      with regulated delayed attenuation to induce immune responses against PspA.
AB  - Increasing the immunogenicity to delivered antigens by recombinant attenuated
      Salmonella vaccines (RASV) has been the subject of intensive study. With this
      goal in mind, we have designed and constructed a new generation of RASV that
      exhibit regulated delayed attenuation. These vaccine strains are phenotypically
      wild type at the time of immunization and become attenuated after colonization of
      host tissues. The vaccine strains are grown under conditions that allow
      expression of genes required for optimal invasion and colonization of host
      tissues. Once established in the host, these virulence genes are turned off,
      fully attenuating the vaccine strain. In this study, we compared 2 of our newly
      developed regulated delayed attenuation Salmonella enterica serovar Typhimurium
      strains chi9088 and chi9558 with the Deltacya Deltacrp Deltaasd strain chi8133,
      for their abilities to express and present a secreted form of the alpha-helical
      region of pneumococcal surface protein A (PspA) to the mouse immune system. All 3
      strains induced high levels of serum antibodies specific for PspA as well as to
      Salmonella antigens in orally immunized mice. However, both RASVs expressing
      delayed attenuation elicited significantly greater anti-PspA immune responses,
      including serum IgG and T cell secretion of IL-4 and IFN-gamma, than other
      groups. Also, vaccination with delayed attenuation strains resulted in a greater
      degree of protection against Streptococcus pneumoniae challenge than in mice
      vaccinated with chi8133 (71-86% vs. 21% survival, P </= 0.006). Together, the
      results demonstrate that the regulated attenuation strategy results in highly
      immunogenic antigen delivery vectors for oral vaccination.

PMID- 19114650
TI  - Unliganded gating of acetylcholine receptor channels.
AB  - We estimated the unliganded opening and closing rate constants of neuromuscular
      acetylcholine receptor-channels (AChRs) having mutations that increased the
      gating equilibrium constant. For some mutant combinations, spontaneous openings
      occurred in clusters. For 25 different constructs, the unliganded gating
      equilibrium constant (E(0)) was correlated with the product of the predicted fold
      increase in the diliganded gating equilibrium constant caused by each mutation
      alone. We estimate that (i) E(0) for mouse, wild-type alpha(2)beta delta epsilon
      AChRs is approximately 1.15 x 10(-7); (ii) unliganded AChRs open for
      approximately 80 micros, once every approximately 15 min; (iii) the affinity for
      ACh of the O(pen) conformation is approximately 10 nM, or approximately 15,600
      times greater than for the C(losed) conformation; (iv) the ACh-monoliganded
      gating equilibrium constant is approximately 1.7 x 10(-3); (v) the C-->O
      isomerization reduces substantially ACh dissociation, but only slightly increases
      association; and (vi) ACh provides only approximately 0.9 k(B)T more binding
      energy per site than carbamylcholine but approximately 3.1 k(B)T more than
      choline, mainly because of a low O conformation affinity. Most mutations of
      binding site residue alphaW149 increase E(0). We estimate that the mutation
      alphaW149F reduces the ACh affinity of C only by 13-fold, but of O by 190-fold.
      Rate-equilibrium free-energy relationships for different regions of the protein
      show similar slopes (Phi values) for un- vs. diliganded gating, which suggests
      that the conformational pathway of the gating structural change is fundamentally
      the same with and without agonists. Agonist binding is a perturbation that (like
      most mutations) changes the energy, but not the mechanism, of the gating
      conformational change.

PMID- 19114651
TI  - A primitive Late Pliocene cheetah, and evolution of the cheetah lineage.
AB  - The cheetah lineage is a group of large, slender, and long-limbed cats with a
      distinctive skull and dental morphology, of which only the extant cheetah
      (Acinonyx jubatus) is present today. The lineage is characterized by having
      abbreviated, tall, and domed crania, and a trenchant dentition with a much
      reduced, posteriorly placed protocone on the upper carnassial. In this article,
      we report on a new discovery of a Late Pliocene specimen from China with an
      estimated age of approximately 2.2-2.5 million years, making it one of the oldest
      specimens known to date. A cladistic analysis confirmed that it is the most
      primitive cheetah known, and it shares a number of unambiguous derived cranial
      traits with the Acinonyx lineage, but has more primitive dentition than
      previously known cheetahs, demonstrating that the many unusual skull and dental
      characters hitherto considered characteristic of cheetahs evolved in a gradual
      fashion. Isolated teeth of primitive cheetahs may not be recognizable as such,
      but can be confused with, for instance, those of leopards or other similar-sized
      pantherine cats or pumas. The age and morphology of the new specimen supports an
      Old World origin of the cheetah lineage, not a New World one, as has been
      suggested. We name the new species Acinonyx kurteni in honor of the late Bjorn
      Kurten.

PMID- 19114652
TI  - Structurally diverse natural products that cause potassium leakage trigger
      multicellularity in Bacillus subtilis.
AB  - We report a previously undescribed quorum-sensing mechanism for triggering
      multicellularity in Bacillus subtilis. B. subtilis forms communities of cells
      known as biofilms in response to an unknown signal. We discovered that biofilm
      formation is stimulated by a variety of small molecules produced by bacteria-
      including the B. subtilis nonribosomal peptide surfactin--that share the ability
      to induce potassium leakage. Natural products that do not cause potassium leakage
      failed to induce multicellularity. Small-molecule-induced multicellularity was
      prevented by the addition of potassium, but not sodium or lithium. Evidence is
      presented that potassium leakage stimulates the activity of a membrane protein
      kinase, KinC, which governs the expression of genes involved in biofilm
      formation. We propose that KinC responds to lowered intracellular potassium
      concentration and that this is a quorum-sensing mechanism that enables B.
      subtilis to respond to related and unrelated bacteria.

PMID- 19114653
TI  - A regulatory interplay between miR-27a and Runx1 during megakaryopoiesis.
AB  - The transcription factor Runx1 is a key regulator of definitive hematopoiesis in
      the embryo and the adult. Lineage-specific expression of Runx1 involves
      transcription and post-transcription control through usage of alternative
      promoters and diverse 3'UTR isoforms, respectively. We identified and mapped
      microRNA (miR) binding sites on Runx1 3'UTR and show that miR-27a, miR-9, miR
      18a, miR-30c, and miR-199a* bind and post-transcriptionally attenuate expression
      of Runx1. miR-27a impacts on both the shortest (0.15 kb) and longest (3.8 kb)
      3'UTRs and, along with additional miRs, might contribute to translation
      attenuation of Runx1 mRNA in the myeloid cell line 416B. Whereas levels of Runx1
      mRNA in 416B and the B cell line 70Z were similar, the protein levels were not.
      Large amounts of Runx1 protein were found in 70Z cells, whereas only minute
      amounts of Runx1 protein were made in 416B cells and overexpression of Runx1 in
      416B induced terminal differentiation associated with megakaryocytic markers.
      Induction of megakaryocytic differentiation in K562 cells by 12-o
      tetradecanoylphorbol-13-acetate markedly increased miR-27a expression,
      concomitantly with binding of Runx1 to miR-27a regulatory region. The data
      indicate that miR-27a plays a regulatory role in megakaryocytic differentiation
      by attenuating Runx1 expression, and that, during megakaryopoiesis, Runx1 and miR
      27a are engaged in a feedback loop involving positive regulation of miR-27a
      expression by Runx1.

PMID- 19114654
TI  - Folding energy landscape and network dynamics of small globular proteins.
AB  - The folding energy landscape of proteins has been suggested to be funnel-like
      with some degree of ruggedness on the slope. How complex the landscape, however,
      is still rather unclear. Many experiments for globular proteins suggested
      relative simplicity, whereas molecular simulations of shorter peptides implied
      more complexity. Here, by using complete conformational sampling of 2 globular
      proteins, protein G and src SH3 domain and 2 related random peptides, we
      investigated their energy landscapes, topological properties of folding networks,
      and folding dynamics. The projected energy surfaces of globular proteins were
      funneled in the vicinity of the native but also have other quite deep, accessible
      minima, whereas the randomized peptides have many local basins, including some
      leading to seriously misfolded forms. Dynamics in the denatured part of the
      network exhibited basin-hopping itinerancy among many conformations, whereas the
      protein reached relatively well-defined final stages that led to their native
      states. We also found that the folding network has the hierarchic nature
      characterized by the scale-free and the small-world properties.

PMID- 19114655
TI  - DGCR8-dependent microRNA biogenesis is essential for skin development.
AB  - MicroRNAs play important roles in animal development. Numerous conditional
      knockout (cKO) studies of Dicer have been performed to interrogate the functions
      of microRNA during mammalian development. However, because Dicer was recently
      implicated in the biogenesis of endogenous siRNAs in mammals, it raises the
      question whether the Dicer cKO defects can be attributable to the loss of
      microRNAs. Previously, we and others conditionally targeted Dicer and identified
      its critical roles in embryonic skin morphogenesis. Here, we focus explicitly on
      microRNAs by taking a parallel strategy with Dgcr8, encoding an essential
      component of the microprocessor complex that is exclusively required for microRNA
      biogenesis. With this comparative analysis, we show definitively that the Dicer-
      and Dgcr8-null skin defects are both striking and indistinguishable. By deep
      sequencing analysis of microRNA depletion in both Dicer- and Dgcr8-null skin, we
      demonstrate that most abundantly expressed skin microRNAs are dependent on both
      Dicer and DGCR8. Our results underscore a specific importance of microRNAs in
      controlling mammalian skin development.

PMID- 19114656
TI  - A phosphorylation-dependent intramolecular interaction regulates the membrane
      association and activity of the tumor suppressor PTEN.
AB  - The PI 3-phosphatase PTEN (phosphatase and tensin homologue deleted on chromosome
      10), one of the most important tumor suppressors, must associate with the plasma
      membrane to maintain appropriate steady-state levels of phosphatidylinositol
      3,4,5-triphosphate. Yet the mechanism of membrane binding has received little
      attention and the key determinants that regulate localization, a
      phosphatidylinositol 4,5-bisphosphate (PIP(2)) binding motif and a cluster of
      phosphorylated C-terminal residues, were not included in the crystal structure.
      We report that membrane binding requires PIP(2) and show that phosphorylation
      regulates an intramolecular interaction. A truncated version of the enzyme,
      PTEN(1-351), bound strongly to the membrane, an effect that was reversed by co
      expression of the remainder of the molecule, PTEN(352-403). The separate
      fragments associated in vitro, an interaction dependent on phosphorylation of the
      C-terminal cluster, a portion of the PIP(2) binding motif, integrity of the
      phosphatase domain, and the CBR3 loop. Our investigation provides direct evidence
      for a model in which PTEN switches between open and closed states and
      phosphorylation favors the closed conformation, thereby regulating localization
      and function. Small molecules targeting these interactions could potentially
      serve as therapeutic agents in antagonizing Ras or PI3K-driven tumors. The study
      also stresses the importance of determining the structure of the native enzyme.

PMID- 19114657
TI  - From the Cover: Whole-genome association study identifies STK39 as a hypertension
      susceptibility gene.
AB  - Hypertension places a major burden on individual and public health, but the
      genetic basis of this complex disorder is poorly understood. We conducted a
      genome-wide association study of systolic and diastolic blood pressure (SBP and
      DBP) in Amish subjects and found strong association signals with common variants
      in a serine/threonine kinase gene, STK39. We confirmed this association in an
      independent Amish and 4 non-Amish Caucasian samples including the Diabetes
      Genetics Initiative, Framingham Heart Study, GenNet, and Hutterites (meta
      analysis combining all studies: n = 7,125, P < 10(-6)). The higher BP-associated
      alleles have frequencies > 0.09 and were associated with increases of 3.3/1.3 mm
      Hg in SBP/DBP, respectively, in the Amish subjects and with smaller but
      consistent effects across the non-Amish studies. Cell-based functional studies
      showed that STK39 interacts with WNK kinases and cation-chloride cotransporters,
      mutations in which cause monogenic forms of BP dysregulation. We demonstrate that
      in vivo, STK39 is expressed in the distal nephron, where it may interact with
      these proteins. Although none of the associated SNPs alter protein structure, we
      identified and experimentally confirmed a highly conserved intronic element with
      allele-specific in vitro transcription activity as a functional candidate for
      this association. Thus, variants in STK39 may influence BP by increasing STK39
      expression and consequently altering renal Na(+) excretion, thus unifying rare
      and common BP-regulating alleles in the same physiological pathway.

PMID- 19114658
TI  - Resolving cadherin interactions and binding cooperativity at the single-molecule
      level.
AB  - The cadherin family of Ca(2+)-dependent cell adhesion proteins are critical for
      the morphogenesis and functional organization of tissues in multicellular
      organisms, but the molecular interactions between cadherins that are at the core
      of cell-cell adhesion are a matter of considerable debate. A widely-accepted
      model is that cadherins adhere in 3 stages. First, the functional unit of
      cadherin adhesion is a cis dimer formed by the binding of the extracellular
      regions of 2 cadherins on the same cell surface. Second, formation of low
      affinity trans interactions between cadherin cis dimers on opposing cell surfaces
      initiates cell-cell adhesion. Third, lateral clustering of cadherins
      cooperatively strengthens intercellular adhesion. Evidence of these cadherin
      binding states during adhesion is, however, contradictory, and evidence for
      cooperativity is lacking. We used single-molecule structural (fluorescence
      resonance energy transfer) and functional (atomic force microscopy) assays to
      demonstrate directly that cadherin monomers interact via their N-terminal EC1
      domain to form trans adhesive complexes. We could not detect the formation of
      cadherin cis dimers, but found that increasing the density of cadherin monomers
      cooperatively increased the probability of trans adhesive binding.

PMID- 19114659
TI  - Simple prediction of interaction strengths in complex food webs.
AB  - Darwin's classic image of an "entangled bank" of interdependencies among species
      has long suggested that it is difficult to predict how the loss of one species
      affects the abundance of others. We show that for dynamical models of
      realistically structured ecological networks in which pair-wise consumer-resource
      interactions allometrically scale to the (3/4) power--as suggested by metabolic
      theory--the effect of losing one species on another can be predicted well by
      simple functions of variables easily observed in nature. By systematically
      removing individual species from 600 networks ranging from 10-30 species, we
      analyzed how the strength of 254,032 possible pair-wise species interactions
      depended on 90 stochastically varied species, link, and network attributes. We
      found that the interaction strength between a pair of species is predicted well
      by simple functions of the two species' biomasses and the body mass of the
      species removed. On average, prediction accuracy increases with network size,
      suggesting that greater web complexity simplifies predicting interaction
      strengths. Applied to field data, our model successfully predicts interactions
      dominated by trophic effects and illuminates the sign and magnitude of important
      nontrophic interactions.

PMID- 19114660
TI  - PKC eta regulates occludin phosphorylation and epithelial tight junction
      integrity.
AB  - PKC eta is expressed predominantly in the epithelial tissues; however, its role
      in the regulation of epithelial tight junctions (TJs) is unknown. We present
      evidence that PKC eta phosphorylates occludin on threonine residues (T403 and
      T404) and plays a crucial role in the assembly and/or maintenance of TJs in Caco
      2 and MDCK cell monolayers. Inhibition of PKC eta by specific pseudo substrate
      inhibitor or knockdown of PKC eta by specific shRNA disrupts the junctional
      distribution of occludin and ZO-1 and compromises the epithelial barrier
      function. Expression of dominant negative, PKC eta(K394R) disrupts the TJ and
      barrier function, whereas wild-type PKC eta and constitutively active PKC
      eta(A161E) enhance the TJ integrity. Inhibition and knockdown of PKC eta or
      expression of PKC eta(K394R) induce dephosphorylation of occludin on threonine
      residues, whereas active PKC eta elevates occludin phosphorylation. PKC eta
      directly interacts with the C-terminal domain of occludin and phosphorylates it
      on highly conserved T403 and T404. T403/404A mutations result in the loss of
      occludin's ability to localize at the TJs, whereas T403/404D mutations attenuates
      the PKC eta inhibitor-mediated redistribution of occludin from the intercellular
      junctions. These results reveal an important mechanism of epithelial TJ
      regulation by PKC eta.

PMID- 19114661
TI  - An empirical explanation of aperture effects.
AB  - The perceived direction of a moving line changes, often markedly, when viewed
      through an aperture. Although several explanations of this remarkable effect have
      been proposed, these accounts typically focus on the percepts elicited by a
      particular type of aperture and offer no biological rationale. Here, we test the
      hypothesis that to contend with the inherently ambiguous nature of motion stimuli
      the perceived direction of objects moving behind apertures of different shapes is
      determined by a wholly empirical strategy of visual processing. An analysis of
      moving line stimuli generated by objects projected through apertures shows that
      the directions of motion subjects report in psychophysical testing is accounted
      for by the frequency of occurrence of the 2D directions of stimuli generated by
      simulated 3D sources. The completeness of these predictions supports the
      conclusion that the direction of perceived motion is fully determined by
      accumulated behavioral experience with sources whose physical motions cannot be
      conveyed by image sequences as such.

PMID- 19114662
TI  - The yeast Sup35NM domain propagates as a prion in mammalian cells.
AB  - Prions are infectious, self-propagating amyloid-like protein aggregates of
      mammals and fungi. We have studied aggregation propensities of a yeast prion
      domain in cell culture to gain insights into general mechanisms of prion
      replication in mammalian cells. Here, we report the artificial transmission of a
      yeast prion across a phylogenetic kingdom. HA epitope-tagged yeast Sup35p prion
      domain NM was stably expressed in murine neuroblastoma cells. Although
      cytosolically expressed NM-HA remained soluble, addition of fibrils of
      bacterially produced Sup35NM to the medium efficiently induced appearance of
      phenotypically and biochemically distinct NM-HA aggregates that were inherited by
      daughter cells. Importantly, NM-HA aggregates also were infectious to recipient
      mammalian cells expressing soluble NM-HA and, to a lesser extent, to yeast. The
      fact that the yeast Sup35NM domain can propagate as a prion in neuroblastoma
      cells strongly argues that cellular mechanisms support prion-like inheritance in
      the mammalian cytosol.

PMID- 19114663
TI  - Viral RNA polymerase complex promotes optimal growth of 1918 virus in the lower
      respiratory tract of ferrets.
AB  - The 1918 influenza pandemic was the most devastating outbreak of infectious
      disease in human history, accounting for about 50 million deaths worldwide. In
      addition to a significant number of cases of secondary bacterial pneumonia, this
      highly pathogenic strain of influenza A virus caused fatal primary viral
      pneumonia. To identify the viral gene(s) chiefly responsible for the high
      virulence of the 1918 virus, we generated a series of reassortants between the
      1918 virus and a contemporary human H1N1 virus (A/Kawasaki/173/2001; K173) using
      reverse genetics. We then assessed their virulence properties in ferrets, a model
      closely resembling humans in terms of sensitivity to influenza virus infection
      and pattern of spread after intranasal inoculation. Substitution of single genes
      from the 1918 virus in the genetic background of K173 virus did not markedly
      alter the pattern of infection. That is, the reassortants grew well in nasal
      turbinates, but only sporadically (if at all) in the trachea and lungs. One
      exception was the 1918PB1/K173 reassortant, which replicated efficiently in lung
      tissues as well as the upper respiratory tract. A reassortant virus expressing
      the 1918 viral RNA polymerase complex (PA, PB1, and PB2) and nucleoprotein showed
      virulence properties in the upper and lower respiratory tracts of ferrets that
      closely resembled those of wild-type 1918 virus. Our findings strongly implicate
      the viral RNA polymerase complex as a major determinant of the pathogenicity of
      the 1918 pandemic virus. This new insight may aid in identifying virulence
      factors in future pandemic viruses that could be targeted with antiviral
      compounds.

PMID- 19114664
TI  - Force generation by a dynamic Z-ring in Escherichia coli cell division.
AB  - FtsZ, a bacterial homologue of tubulin, plays a central role in bacterial cell
      division. It is the first of many proteins recruited to the division site to form
      the Z-ring, a dynamic structure that recycles on the time scale of seconds and is
      required for division to proceed. FtsZ has been recently shown to form rings
      inside tubular liposomes and to constrict the liposome membrane without the
      presence of other proteins, particularly molecular motors that appear to be
      absent from the bacterial proteome. Here, we propose a mathematical model for the
      dynamic turnover of the Z-ring and for its ability to generate a constriction
      force. Force generation is assumed to derive from GTP hydrolysis, which is known
      to induce curvature in FtsZ filaments. We find that this transition to a curved
      state is capable of generating a sufficient force to drive cell-wall invagination
      in vivo and can also explain the constriction seen in the in vitro liposome
      experiments. Our observations resolve the question of how FtsZ might accomplish
      cell division despite the highly dynamic nature of the Z-ring and the lack of
      molecular motors.

PMID- 19114665
TI  - Lymphoid tissue inducer-like cells are an innate source of IL-17 and IL-22.
AB  - The interleukin (IL) 17 family of cytokines has emerged to be critical for host
      defense as well as the pathogenesis of autoimmune and autoinflammatory disorders,
      and serves to link adaptive and innate responses. Recent studies have identified
      a new subset of T cells that selectively produce IL-17 (Th17 cells; Bettelli, E.,
      T. Korn, and V.K. Kuchroo. 2007. Curr. Opin. Immunol. 19:652-657; Kolls, J.K.,
      and A. Linden. 2004. Immunity. 21:467-476), but the regulation of IL-17
      production by innate immune cells is less well understood. We report that in
      vitro stimulation with IL-23 induced IL-17 production by recombination activating
      gene (Rag) 2(-/-) splenocytes but not Rag2(-/-) common gamma chain(-/-)
      splenocytes. We found that a major source of IL-17 was CD4(+)CD3(-)NK1.1(-)CD11b(
      )Gr1(-)CD11c(-)B220(-) cells, a phenotype that corresponds to lymphoid tissue
      inducer-like cells (LTi-like cells), which constitutively expressed the IL-23
      receptor, aryl hydrocarbon receptor, and CCR6. In vivo challenge with the yeast
      cell wall product zymosan rapidly induced IL-17 production in these cells.
      Genetic deletion of signal transducer and activator of transcription 3 reduced
      but did not abrogate IL-17 production in LTi-like cells. Thus, it appears that
      splenic LTi-like cells are a rapid source of IL-17 and IL-22, which might
      contribute to dynamic organization of secondary lymphoid organ structure or host
      defense.

PMID- 19114666
TI  - Chemerin expression marks early psoriatic skin lesions and correlates with
      plasmacytoid dendritic cell recruitment.
AB  - Psoriasis is a type I interferon-driven T cell-mediated disease characterized by
      the recruitment of plasmacytoid dendritic cells (pDC) into the skin. The
      molecules involved in pDC accumulation in psoriasis lesions are unknown. Chemerin
      is the only inflammatory chemotactic factor that is directly active on human
      blood pDC in vitro. The aim of this study was to evaluate the role of the
      chemerin/ChemR23 axis in the recruitment of pDC in psoriasis skin. Prepsoriatic
      skin adjacent to active lesions and early lesions were characterized by a strong
      expression of chemerin in the dermis and by the presence of CD15(+) neutrophils
      and CD123(+)/BDCA-2(+)/ChemR23(+) pDC. Conversely, skin from chronic plaques
      showed low chemerin expression, segregation of neutrophils to epidermal
      microabscesses, and few pDC in the dermis. Chemerin expression was localized
      mainly in fibroblasts, mast cells, and endothelial cells. Fibroblasts cultured
      from skin of psoriatic lesions expressed higher levels of chemerin messenger RNA
      and protein than fibroblasts from uninvolved psoriatic skin or healthy donors and
      promoted pDC migration in vitro in a chemerin-dependent manner. Therefore,
      chemerin expression specifically marks the early phases of evolving skin
      psoriatic lesions and is temporally strictly associated with pDC. These results
      support a role for the chemerin/ChemR23 axis in the early phases of psoriasis
      development.

PMID- 19114667
TI  - A role for the IgH intronic enhancer E mu in enforcing allelic exclusion.
AB  - The intronic enhancer (E mu) of the immunoglobulin heavy chain (IgH) locus is
      critical for V region gene assembly. To determine E mu's subsequent functions, we
      created an Igh allele with assembled V(H) gene but with E mu removed. In mice
      homozygous for this E mu-deficient allele, B cell development was normal and
      indistinguishable from that of mice with the same V(H) knockin and E mu intact.
      In mice heterozygous for the E mu-deficient allele, however, allelic exclusion
      was severely compromised. Surprisingly, this was not a result of reduced
      suppression of V-DJ assembly on the second allele. Rather, the striking breakdown
      in allelic exclusion took place at the pre-B to immature B cell transition. These
      findings reveal both an important role for E mu in influencing the fate of newly
      arising B cells and a second checkpoint for allelic exclusion.

PMID- 19114668
TI  - Natural agonists for aryl hydrocarbon receptor in culture medium are essential
      for optimal differentiation of Th17 T cells.
AB  - Th17 cell differentiation is dependent on interleukin (IL)-6 and transforming
      growth factor (TGF)-beta, and it is modulated by activation of the aryl
      hydrocarbon receptor (AhR). In this study, we show that differentiation of Th17
      cells, but not Th1 or induced regulatory T (iT reg) cells, is increased by
      endogenous AhR agonists present in culture medium. Th17 development from wild
      type mice is suboptimal in the presence of the AhR antagonist CH-223191, similar
      to the situation in AhR-deficient mice, which show attenuated IL-17 production
      and no IL-22 production. The presence of natural AhR agonists in culture medium
      is also revealed by the induction of CYP1A1, a downstream target of AhR
      activation. However, the most commonly used medium, RPMI, supports very low
      levels of Th17 polarization, whereas Iscove's modified Dulbecco's medium, a
      medium richer in aromatic amino acids, which give rise to AhR agonists,
      consistently results in higher Th17 expansion in both mouse and human cells. The
      relative paucity of AhR agonists in RPMI medium, coupled with the presence of
      factors conducive to IL-2 activation and enhanced Stat5 phosphorylation, conspire
      against optimal Th17 differentiation. Our data emphasize that AhR activation
      plays an essential part in the development of Th17 cells and provide a rational
      explanation for the poor in vitro polarization of Th17 cells that is reported in
      the majority of publications for both mouse and human cells.

PMID- 19114669
TI  - Identification of the human eosinophil lineage-committed progenitor: revision of
      phenotypic definition of the human common myeloid progenitor.
AB  - To establish effective therapeutic strategies for eosinophil-related disorders,
      it is critical to understand the developmental pathway of human eosinophils. In
      mouse hematopoiesis, eosinophils originate from the eosinophil lineage-committed
      progenitor (EoP) that has been purified downstream of the granulocyte/macrophage
      progenitor (GMP). We show that the EoP is also isolatable in human adult bone
      marrow. The previously defined human common myeloid progenitor (hCMP) population
      (Manz, M.G., T. Miyamoto, K. Akashi, and I.L. Weissman. 2002. Proc. Natl. Acad.
      Sci. USA. 99:11872-11877) was composed of the interleukin 5 receptor alpha
      chain(+) (IL-5Ralpha(+)) and IL-5Ralpha(-) fractions, and the former was the
      hEoP. The IL-5Ralpha(+)CD34(+)CD38(+)IL-3Ralpha(+)CD45RA(-) hEoPs gave rise
      exclusively to pure eosinophil colonies but never differentiated into basophils
      or neutrophils. The IL-5Ralpha(-) hCMP generated the hEoP together with the hGMP
      or the human megakaryocyte/erythrocyte progenitor (hMEP), whereas hGMPs or hMEPs
      never differentiated into eosinophils. Importantly, the number of hEoPs increased
      up to 20% of the conventional hCMP population in the bone marrow of patients with
      eosinophilia, suggesting that the hEoP stage is involved in eosinophil
      differentiation and expansion in vivo. Accordingly, the phenotypic definition of
      hCMP should be revised to exclude the hEoP; an "IL-5Ralpha-negative" criterion
      should be added to define more homogenous hCMP. The newly identified hEoP is a
      powerful tool in studying pathogenesis of eosinophilia and could be a therapeutic
      target for a variety of eosinophil-related disorders.

PMID- 19114670
TI  - C-reactive protein and coronary heart disease: predictive test or therapeutic
      target?
AB  - BACKGROUND: The hepatocyte-derived acute-phase reactant C-reactive protein (CRP)
      has been the subject of intense research over the last 2 decades for its possible
      role in the pathogenesis of cardiovascular diseases. This research has spawned
      interest in the use of the blood concentration of CRP for predicting a first
      coronary heart disease (CHD) event, which has been made possible with the
      development of high-sensitivity CRP (hsCRP) assays that can measure the typically
      low concentrations of CRP that circulate in the absence of an overt infective or
      inflammatory episode, and as a potential causal factor that might be targeted
      therapeutically. The research has encompassed observational and genetic
      epidemiology, basic science studies with cells and tissues, experiments with
      animal models and humans, and randomized trials (although not of specific CRP
      lowering therapies as yet). CONTENT: We focus on investigations of the potential
      role of small differences in basal hsCRP concentration seen in healthy
      individuals and the relationship of such differences to the long-term risk of a
      first CHD event, rather than on research devoted to the high acute-phase CRP
      concentrations, which occur after acute atherothrombotic events and can influence
      the severity of ischemic tissue damage and the subsequent prognosis. We
      concentrate mainly on research findings at the translational interface and draw
      on evidence from human observational and genetic epidemiology, as well as from
      randomized trials. CONCLUSIONS: As the field matures from one of discovery to an
      evaluative science, the development of possible clinical applications requires a
      sharpening of focus on and a critical appraisal of the strengths and deficiencies
      of the accumulated evidence. Such assessments require attention to both the
      current state of affairs and the design of future research, so that the existing
      uncertainties about the utility of CRP in predicting CHD and its role in causing
      this disease can be resolved.

PMID- 19114671
TI  - In vitro antimicrobial activity of a new cephalosporin, ceftaroline, and
      determination of quality control ranges for MIC testing.
AB  - The spectrum of activity of ceftaroline was evaluated against 1,247 bacterial
      isolates representing 44 different species or phenotypic groups. For the majority
      of species, the activity of ceftaroline was comparable or superior to that of
      ceftriaxone. MIC and/or disk diffusion quality control ranges of ceftaroline were
      determined for five standard ATCC reference strains.

PMID- 19114672
TI  - A 10-year survey of antifungal susceptibility of candidemia isolates from
      intensive care unit patients in Greece.
AB  - This study retrospectively reviews the susceptibility of 135 baseline ICU
      candidemia isolates (from 1997 to 2007) to nine antifungals as determined by the
      AFST-EUCAST microdilution method and identifies the most frequent causative
      agents of confirmed point-source candidemia outbreaks in local intensive care
      units. A minority of common and rare Candida species displayed decreased
      susceptibility to all antifungals.

PMID- 19114673
TI  - Antiretroviral concentrations in breast-feeding infants of mothers receiving
      highly active antiretroviral therapy.
AB  - There are limited data describing the concentrations of zidovudine, lamivudine,
      and nevirapine in nursing infants as a result of transfer via breast milk. The
      Kisumu Breastfeeding Study is a phase IIb open-label trial of prenatal,
      intrapartum, and postpartum maternal treatment with zidovudine, lamivudine, and
      nevirapine from 34 weeks of gestation to 6 months postpartum. In a
      pharmacokinetic substudy, maternal plasma, breast milk, and infant dried blood
      spots were collected for drug assay on the day of delivery and at 2, 6, 14, and
      24 weeks after delivery. Sixty-seven mother-infant pairs were enrolled. The
      median concentrations in breast milk of zidovudine, lamivudine, and nevirapine
      during the study period were 14 ng/ml, 1,214 ng/ml, and 4,546 ng/ml,
      respectively. Zidovudine was not detectable in any infant plasma samples obtained
      after the day of delivery, while the median concentrations in infant plasma
      samples from postpartum weeks 2, 6, and 14 were 67 ng/ml, 32 ng/ml, and 24 ng/ml
      for lamivudine and 987 ng/ml, 1,032 ng/ml, and 734 ng/ml for nevirapine,
      respectively. Therefore, lamivudine and nevirapine, but not zidovudine, are
      transferred to infants via breast milk in biologically significant
      concentrations. The extent and effect of infant drug exposure via breast milk
      must be well understood in order to evaluate the benefits and risks of maternal
      antiretroviral use during lactation.

PMID- 19114675
TI  - Bronchopulmonary disposition of micafungin in healthy adult volunteers.
AB  - By way of bronchoscopy and bronchoalveolar lavage, intrapulmonary steady-state
      concentrations of micafungin administered at 150 mg daily to 15 healthy
      volunteers were determined at 4, 12, and 24 h after the third dose. The
      micafungin disposition was predominantly intracellular, with approximately 106%
      penetration into alveolar macrophages and 5% penetration into epithelial lining
      fluid.

PMID- 19114674
TI  - SC29EK, a peptide fusion inhibitor with enhanced alpha-helicity, inhibits
      replication of human immunodeficiency virus type 1 mutants resistant to
      enfuvirtide.
AB  - Peptides derived from the alpha-helical domains of human immunodeficiency virus
      (HIV) type 1 (HIV-1) gp41 inhibit HIV-1 fusion to the cell membrane. Enfuvirtide
      (T-20) is a peptide-based drug that targets the step of HIV fusion, and as such,
      it effectively suppresses the replication of HIV-1 strains that are either wild
      type or resistant to multiple reverse transcriptase and/or protease inhibitors.
      However, HIV-1 variants with T-20 resistance have emerged; therefore, the
      development of new and potent inhibitors is urgently needed. We have developed a
      novel HIV fusion inhibitor, SC34EK, which is a gp41-derived 34-amino-acid peptide
      with glutamate (E) and lysine (K) substitutions on its solvent-accessible site
      that stabilize its alpha-helicity. Importantly, SC34EK effectively inhibits the
      replication of T-20-resistant HIV-1 strains as well as wild-type HIV-1. In this
      report, we introduce SC29EK, a 29-amino-acid peptide that is a shorter variant of
      SC34EK. SC29EK blocked the replication of T-20-resistant HIV-1 strains and
      maintained antiviral activity even in the presence of high serum concentrations
      (up to 50%). Circular dichroism analysis revealed that the alpha-helicity of
      SC29EK was well maintained, while that of the parental peptide, C29, which showed
      moderate and reduced inhibition of wild-type and T-20-resistant HIV-1 strains,
      was lower. Our results show that the alpha-helicity in a peptide-based fusion
      inhibitor is a key factor for activity and enables the design of short peptide
      inhibitors with improved pharmacological properties.

PMID- 19114676
TI  - Pharmacodynamics of tigecycline against phenotypically diverse Staphylococcus
      aureus isolates in a murine thigh model.
AB  - Tigecycline is a currently marketed antimicrobial agent with activity against
      resistant gram-positive cocci, including methicillin-resistant Staphylococcus
      aureus (MRSA). Despite the proven efficacy of tigecycline in the treatment of
      infections caused by these pathogens, questions remain as to the exposure
      response relationship best associated with its efficacy. The purpose of this
      study was to define this relationship against seven distinct S. aureus isolates
      by using a neutropenic murine thigh model. Single-dose pharmacokinetics were
      evaluated, and free drug exposures were calculated after determination of protein
      binding. Doses of 1.56 to 400 mg/kg of body weight divided 1 to 8 times daily
      were administered against two methicillin-susceptible S. aureus isolates, two
      hospital-associated MRSA (HA-MRSA) isolates, and three community-associated (CA
      MRSA) isolates. Tigecycline pharmacokinetics were best described by a two
      compartment model, with a mean half-life of 9.9 h. Protein binding was dose
      dependent (range, 92.9 to 81.2%). MICs were 0.25 microg/ml for all isolates,
      except for HA-MRSA 56 (MIC, 0.5 microg/ml) and CA-MRSA 156 (MIC, 0.125
      microg/ml). Tigecycline displayed efficacy against all isolates, producing
      maximum decreases in log(10) numbers of CFU/ml of 1.8 to 2.3 from 0-h controls.
      Mean correlation coefficients for free-drug (f) concentration exposures derived
      from the parameters fT>MIC (the percentage of time during which the concentration
      of f remains above the MIC), fC(max)/MIC (the ratio of the maximum concentration
      of f to the MIC), and fAUC/MIC (the ratio of the area under the concentration
      time curve of f to the MIC) were 0.622, 0.812, and 0.958, respectively. Values
      for the mean effective exposure index at 80% (EI(80)) and 50% (EI(50)) for
      fAUC/MIC were 5.4 microg/ml (range, 2.8 to 13 microg/ml) and 2.6 microg/ml
      (range, 0.6 to 5.1 microg/ml), respectively. Experiments with nonneutropenic mice
      infected with CA-MRSA 156 resulted in maximum kill at all fAUC/MIC exposures
      tested (1.8 to 8.8 microg/ml). The fAUC/MIC ratio is the pharmacodynamic
      parameter most predictive of tigecycline efficacy. Furthermore, the presence of a
      functioning immune system markedly reduces the required exposure.

PMID- 19114677
TI  - Carbapenem resistance among Pseudomonas aeruginosa strains from India: evidence
      for nationwide endemicity of multiple metallo-beta-lactamase clones (VIM-2, -5, 
      6, and -11 and the newly characterized VIM-18).
AB  - Among 57 metallo-beta-lactamase (MbetaL)-producing Pseudomonas spp. detected in
      India during 2006, five bla(VIM) genes were found, including a newly
      characterized bla(VIM) gene. Pseudomonas aeruginosa strains were clustered in 33
      ribotypes with clones found in multiple hospitals. Several types of bla(VIM-2)
      carrying integrons were detected. The newly characterized variant VIM-18 showed a
      4-amino-acid deletion compared to other VIM variants. In this study, we show that
      VIM-producing Pseudomonas spp. were highly prevalent in India with a great
      diversity of bla(VIM) types and MbetaL-carrying integrons.

PMID- 19114678
TI  - Antimicrobial activity of prulifloxacin tested against a worldwide collection of
      gastroenteritis-producing pathogens, including those causing traveler's diarrhea.
AB  - Prulifloxacin, the prodrug of ulifloxacin (active component), is a newer
      fluoroquinolone with broad activity against enteric and nonenteric gram-negative
      bacilli. Ulifloxacin and other oral comparator agents were tested for activity
      against 582 gastroenteritis strains from global surveillance studies. Ulifloxacin
      was highly active against Escherichia coli, Salmonella spp., Shigella spp.,
      Yersinia spp., Vibrio spp., Aeromonas spp., and Plesiomonas spp. (MIC(50)s and
      MIC(90)s, <or=0.03 microg/ml and <or=0.06 microg/ml, respectively). Only rare
      Aeromonas spp., Campylobacter spp., and E. coli displayed elevated MIC results
      (>or=4 microg/ml). Ciprofloxacin exhibited similar activity but was two- to
      fourfold less potent. Presently approved for clinical use in certain European
      countries and Japan, ulifloxacin was the most active of the antimicrobial agents
      tested against these gastroenteritis-causing pathogens.

PMID- 19114679
TI  - Roles of NF-kappaB activation and peroxisome proliferator-activated receptor
      gamma inhibition in the effect of rifampin on inducible nitric oxide synthase
      transcription in human lung epithelial cells.
AB  - Rifampin (rifampicin), an important antibiotic agent and a major drug used for
      the treatment of tuberculosis, exerts immunomodulatory effects. Previous studies
      have found that rifampin increases inducible nitric oxide (NO) synthase (iNOS)
      expression and NO production. The present study investigated the potential
      mechanism(s) underlying these actions. The incubation of human lung epithelial
      A549 cells with a cytokine mix (interleukin-1beta, tumor necrosis factor alpha,
      and gamma interferon) induced the expression of iNOS mRNA. The addition of
      rifampin increased the iNOS level by 1.9 +/- 0.3-fold at a dose of 10 microg/ml
      (P < 0.01) and by 4.0 +/- 0.3-fold at a dose of 50 microg/ml (P < 0.001).
      Rifampin treatment also affected the transcription factors that regulate iNOS
      mRNA: there was an increased and prolonged degradation of the inhibitory subunit
      of NF-kappaB, a corresponding increase in the level of cytokine-induced DNA
      binding of NF-kappaB (2.1 +/- 0.2-fold), and a decrease in the level of
      expression of peroxisome proliferator-activated receptor gamma (PPARgamma).
      Specifically, the level of PPARgamma expression dropped by 15% in response to
      cytokine stimulation and by an additional 40% when rifampin was added (P <
      0.001). Rifampin had no effect on the activation of mitogen-activated protein
      kinases or the signal transducer and transcription activator (STAT-1). In
      conclusion, rifampin augments NO production by upregulating iNOS mRNA. It also
      increases the level of NF-kappaB activation and decreases the level of PPARgamma
      expression. The increases in the levels of NF-kappaB activation and NO production
      probably contribute to the therapeutic effects of rifampin. However, given the
      role of NF-kappaB in upregulating many inflammatory genes and the roles of
      PPARgamma in downregulating inflammatory genes and in lipid and glucose
      metabolism, these findings have implications for potential adverse effects of
      rifampin in patients with chronic inflammatory diseases and glucose or lipid
      disorders.

PMID- 19114680
TI  - Pharmacokinetics and safety of caspofungin in older infants and toddlers.
AB  - Although information about the efficacy and safety experience with caspofungin at
      50 mg/m(2) daily is available for children and adolescents, the dosing regimen in
      infants and toddlers 3 to 24 months of age has yet to be established. We studied
      the pharmacokinetics and safety of caspofungin at 50 mg/m(2) once daily in nine
      patients 10 to 22 months (median, 13 months) of age with fever and neutropenia
      who received caspofungin once daily for 2 to 21 (mean, 9.3) days. Plasma
      caspofungin concentrations were measured by high-performance liquid
      chromatography assay on days 1 and 4. On day 4, the area under the curve from 0
      to 24 h (AUC(0-24)) was 130.3 microg-h/ml, the peak concentration (C(1)) was 17.2
      microg/ml, and the trough concentration (C(24)) was 1.6 microg/ml. The day 4
      geometric mean ratios (GMRs) and 90% confidence interval (CI) for these
      parameters in infants/toddlers relative to adults were 1.26 (1.06, 1.50), 1.83
      (1.57, 2.14), and 0.81 (0.64, 1.04), respectively. Relative to children (2 to 11
      years of age), the day 4 GMRs (and 90% CI) were 1.13 (0.89, 1.44), 1.10 (0.85,
      1.42), and 1.12 (0.72, 1.76), respectively. The harmonic mean elimination phase
      t(1/2) in infants/toddlers (8.8 h) was reduced approximately 33% relative to
      adults (13.0 h) but was similar to that in children (8.2 h). Clinical adverse
      events occurred in seven patients (78%); none were considered drug related.
      Laboratory adverse events occurred in five patients (56%) and were considered
      drug related in three (33%). There were no infusion-related events or
      discontinuations due to toxicity. Caspofungin at 50 mg/m(2) daily was well
      tolerated in infants and toddlers; the AUC and caspofungin C(24) were generally
      comparable to those in adults receiving caspofungin at 50 mg daily.

PMID- 19114681
TI  - Low-dose inhaled carbon monoxide attenuates the remote intestinal inflammatory
      response elicited by hindlimb ischemia-reperfusion.
AB  - Heme oxygenase (HO) represents the rate-limiting enzyme in the degradation of
      heme into carbon monoxide (CO), iron, and biliverdin. Recent evidence suggests
      that several of the beneficial properties of HO, may be linked to CO. The
      objectives of this study were to determine if low-dose inhaled CO reduces remote
      intestinal leukocyte recruitment, proinflammatory cytokine expression, and
      oxidative stress elicited by hindlimb ischemia-reperfusion (I/R). Male mice
      underwent 1 h of hindlimb ischemia, followed by 3 h of reperfusion. Throughout
      reperfusion, mice were exposed to AIR or AIR + CO (250 ppm). Following
      reperfusion, the distal ileum was exteriorized to assess the intestinal
      inflammatory response by quantifying leukocyte rolling and adhesion in submucosal
      postcapillary venules with the use of intravital microscopy. Ileum samples were
      also analyzed for proinflammatory cytokine expression [tumor necrosis factor
      (TNF)-alpha and interleukin (IL)-1beta] and malondialdehyde (MDA) with the use of
      enzyme-linked immunosorbent assay and thiobarbituric acid reactive substances
      assays, respectively. I/R + AIR led to a significant decrease in leukocyte
      rolling velocity and a sevenfold increase in leukocyte adhesion. This was also
      accompanied by a significant 1.3-fold increase in ileum MDA and 2.3-fold increase
      in TNF-alpha expression. Treatment with AIR + CO led to a significant reduction
      in leukocyte recruitment and TNF-alpha expression elicited by I/R; however, MDA
      levels remained unchanged. Our data suggest that low-dose inhaled CO selectively
      attenuates the remote intestinal inflammatory response elicited by hindlimb I/R,
      yet does not provide protection against intestinal lipid peroxidation. CO may
      represent a novel anti-inflammatory therapeutic treatment to target remote organs
      following acute trauma and/or I/R injury.

PMID- 19114682
TI  - Dual-antibody therapy in advanced colorectal cancer: gather ye rosebuds while ye
      may.

PMID- 19114683
TI  - Fluorouracil, leucovorin, and oxaliplatin with and without cetuximab in the first
      line treatment of metastatic colorectal cancer.
AB  - PURPOSE: This randomized study assessed whether the best overall response rate
      (ORR) of cetuximab combined with oxaliplatin, leucovorin, and fluorouracil
      (FOLFOX-4) was superior to that of FOLFOX-4 alone as first-line treatment for
      metastatic colorectal cancer. The influence of KRAS mutation status was
      investigated. PATIENTS AND METHODS: Patients received cetuximab (400 mg/m(2)
      initial dose followed by 250 mg/m(2)/wk thereafter) plus FOLFOX-4 (oxaliplatin 85
      mg/m(2) on day 1, plus leucovorin 200 mg/m(2) and fluorouracil as a 400 mg/m(2)
      bolus followed by a 600 mg/m(2) infusion during 22 hours on days 1 and 2; n =
      169) or FOLFOX-4 alone (n = 168). Treatment was continued until disease
      progression or unacceptable toxicity. KRAS mutation status was assessed in the
      subset of patients with assessable tumor samples (n = 233). RESULTS: The
      confirmed ORR for cetuximab plus FOLFOX-4 was higher than with FOLFOX-4 alone
      (46% v 36%). A statistically significant increase in the odds for a response with
      the addition of cetuximab to FOLFOX-4 could not be established (odds ratio =
      1.52; P = .064). In patients with KRAS wild-type tumors, the addition of
      cetuximab to FOLFOX-4 was associated with a clinically significant increased
      chance of response (ORR = 61% v 37%; odds ratio = 2.54; P = .011) and a lower
      risk of disease progression (hazard ratio = 0.57; P = .0163) compared with FOLFOX
      4 alone. Cetuximab plus FOLFOX-4 was generally well tolerated. CONCLUSION: KRAS
      mutational status was shown to be a highly predictive selection criterion in
      relation to the treatment decision regarding the addition of cetuximab to FOLFOX
      4 for previously untreated patients with metastatic colorectal cancer.

PMID- 19114684
TI  - Morphology and more specific immunohistochemical stains are fundamental
      prerequisites in detection of unknown primary cancer.

PMID- 19114686
TI  - Barriers to the delivery of psychosocial care for cancer patients: bridging mind
      and body.

PMID- 19114685
TI  - A randomized phase IIIB trial of chemotherapy, bevacizumab, and panitumumab
      compared with chemotherapy and bevacizumab alone for metastatic colorectal
      cancer.
AB  - PURPOSE: Panitumumab, a fully human antibody targeting the epidermal growth
      factor receptor, is active in patients with metastatic colorectal cancer (mCRC).
      This trial evaluated panitumumab added to bevacizumab and chemotherapy
      (oxaliplatin- and irinotecan-based) as first-line treatment for mCRC. PATIENTS
      AND METHODS: Patients were randomly assigned within each chemotherapy cohort to
      bevacizumab and chemotherapy with or without panitumumab 6 mg/kg every 2 weeks.
      The primary end point was progression-free survival (PFS) within the oxaliplatin
      cohort. Tumor assessments were performed every 12 weeks and reviewed centrally.
      RESULTS: A total of 823 and 230 patients were randomly assigned to the
      oxaliplatin and irinotecan cohorts, respectively. Panitumumab was discontinued
      after a planned interim analysis of 812 oxaliplatin patients showed worse
      efficacy in the panitumumab arm. In the final analysis, median PFS was 10.0 and
      11.4 months for the panitumumab and control arms, respectively (HR, 1.27; 95% CI,
      1.06 to 1.52); median survival was 19.4 months and 24.5 months for the
      panitumumab and control arms, respectively. Grade 3/4 adverse events in the
      oxaliplatin cohort (panitumumab v control) included skin toxicity (36% v 1%),
      diarrhea (24% v 13%), infections (19% v 10%), and pulmonary embolism (6% v 4%).
      Increased toxicity without evidence of improved efficacy was observed in the
      panitumumab arm of the irinotecan cohort. KRAS analyses showed adverse outcomes
      for the panitumumab arm in both wild-type and mutant groups. CONCLUSION: The
      addition of panitumumab to bevacizumab and oxaliplatin- or irinotecan-based
      chemotherapy results in increased toxicity and decreased PFS. These combinations
      are not recommended for the treatment of mCRC in clinical practice.

PMID- 19114687
TI  - Radiotherapy after segmental resection of breast cancer with favorable prognostic
      features: 12-year follow-up results of a randomized trial.
AB  - PURPOSE: Postoperative breast irradiation is considered standard after breast
      preserving surgery for cancer. We evaluated the efficacy of radiation therapy in
      the prevention of local recurrence in a patient population that had small-size
      breast cancer with features that suggested low biologic aggressiveness. PATIENTS
      AND METHODS: Women (n = 264) older than 40 years who were treated by breast
      resection with > or = 1 cm of tumor-free margin and axillary nodal dissection
      were randomly assigned to receive or not to receive breast irradiation
      (cumulative dose, 50 Gy) after surgery. The tumor was required to be < or = 20
      mm, node negative, progesterone receptor positive, well to moderately well
      differentiated and unifocal, and of low cell proliferation rate (ie, S phase
      fraction < or = 7% or nuclear Ki-67 expression < 10%) and had to lack an
      extensive intraductal component. The median follow-up time was 12.1 years after
      random assignment. RESULTS: Sixteen (11.6%) and 34 (27.2%) cancers recurred
      locally in the radiotherapy and the control arms, respectively (P = .0013). Time
      to local recurrence was longer in the radiotherapy arm (hazard ratio [HR], 0.36;
      95% CI, 0.20 to 0.65; P = .00071). Twenty-one patients assigned to radiotherapy
      and 26 assigned to control died during the follow-up. There were no differences
      in overall survival time (HR, 0.63; 95% CI, 0.35 to 1.12; P = .11), distant
      disease-free survival (P = .94), or breast cancer-specific survival (P = .56)
      between the radiation therapy and control groups. CONCLUSION: Radiation therapy
      after breast resection reduces the frequency of ipsilateral breast recurrences,
      even among women with small-size breast cancers that have favorable histologic
      features and that are resected with at least a 1-cm margin. Postoperative
      radiotherapy did not significantly improve survival.

PMID- 19114688
TI  - Highly active antiretroviral therapy and the incidence of non-AIDS-defining
      cancers in people with HIV infection.
AB  - PURPOSE: The effect of highly active antiretroviral therapy (HAART) on the
      incidence of non-AIDS-defining cancers (NADCs) is unclear. METHODS: We have
      investigated the occurrence of NADCs in a prospective cohort of 11,112 HIV
      positive individuals, with 71,687 patient-years of follow-up. Standardized
      incidence ratios (SIRs) were calculated using general population incidence data.
      We investigated the effect of calendar period, HIV parameters, and immunologic
      and treatment-related factors on the incidence of these cancers using univariate
      and multivariate analyses. RESULTS: The SIR for all NADCs was 1.96 (95% CI, 1.66
      to 2.29). There was no significant excess in incidence in the pre-HAART era (1983
      to 1995; SIR, 0.95; 95% CI, 0.58 to 1.47). However, the incidence increased in
      the early HAART period (1996 to 2001) and remains elevated in the most recent
      established HAART period (2002 to 2007; SIR, 2.05; 95% CI, 1.51 to 2.72, and SIR
      2.49; 95% CI, 2.00 to 3.07, respectively). Multivariate analysis showed that use
      of HAART (hazard ratio [HR] = 1.64; 95% CI, 1.13 to 2.39) and a nadir CD4 count
      less than 200/microL (HR = 1.67; 95% CI, 1.10 to 2.54) were associated with an
      increased risk. Only the non-nucleoside reverse transcriptase inhibitors (NNRTIs)
      were associated with a significantly increased risk of NADCs (HR = 1.45; 95% CI,
      1.01 to 2.08). Much of this association was attributable to an increased risk of
      Hodgkin's lymphoma with NNRTIs (HR = 2.20; 95% CI, 1.03 to 4.69). CONCLUSION:
      Since the introduction of HAART, there has been a significantly increased risk of
      NADCs, which has now stabilized. A number of factors are associated with this
      increased risk, including HAART use. There may be an association between the use
      of NNRTIs and the development of Hodgkin's lymphoma.

PMID- 19114689
TI  - Predictors of referral for psychosocial services: recommendations from the
      Institute of Medicine report--cancer care for the whole patient.

PMID- 19114690
TI  - When informed, all women do not prefer breast conservation.

PMID- 19114691
TI  - False-positive diagnosis of metastasis on positron emission tomography-computed
      tomography imaging due to hibernoma.

PMID- 19114692
TI  - Dietary patterns and breast cancer recurrence and survival among women with early
      stage breast cancer.
AB  - PURPOSE: To determine the association of dietary patterns with cancer recurrence
      and mortality of early-stage breast cancer survivors. PATIENTS AND METHODS:
      Patients included 1,901 Life After Cancer Epidemiology Study participants
      diagnosed with early-stage breast cancer between 1997 and 2000 and recruited
      primarily from the Kaiser Permanente Northern California Cancer Registry. Diet
      was assessed at cohort entry using a food frequency questionnaire. Two dietary
      patterns were identified: prudent (high intakes of fruits, vegetables, whole
      grains, and poultry) and Western (high intakes of red and processed meats and
      refined grains). Two hundred sixty-eight breast cancer recurrences and 226 all
      cause deaths (128 attributable to breast cancer) were ascertained. Cox
      proportional hazards models were used to estimate hazard ratios (HRs) and 95%
      CIs. RESULTS: Increasing adherence to a prudent dietary pattern was associated
      with a statistically significant decreasing risk of overall death (P trend = .02;
      HR for highest quartile = 0.57; 95% CI, 0.36 to 0.90) and death from non-breast
      cancer causes (P trend = .003; HR for highest quartile = 0.35; 95% CI, 0.17 to
      0.73). In contrast, increasing consumption of a Western dietary pattern was
      related to an increasing risk of overall death (P trend = .05) and death from non
      breast cancer causes (P = .02). Neither dietary pattern was associated with risk
      of breast cancer recurrence or death from breast cancer. These observations were
      generally not modified by physical activity, being overweight, or smoking.
      CONCLUSION: Women diagnosed with early-stage breast cancer might improve overall
      prognosis and survival by adopting more healthful dietary patterns.

PMID- 19114693
TI  - Phosphoinositide-phospholipase C beta1 mono-allelic deletion is associated with
      myelodysplastic syndromes evolution into acute myeloid leukemia.
AB  - PURPOSE: To evaluate the association between the presence of phosphoinositide
      phospholipase C beta1 (PI-PLCbeta1) mono-allelic deletion with the clinical
      outcome of myelodysplastic syndromes (MDS) patients. METHODS: PI-PLCbeta1, PI
      PLCbeta4, and PI-PLCgamma1 cytogenetic investigations were performed on 80 newly
      diagnosed MDS patients (18 low risk, 26 intermediate 1, 18 intermediate 2, 18
      high risk) comparing the results with the clinical outcome of the patients.
      Moreover, fluorescent in situ hybridization results were validated by real-time
      polymerase chain reaction (PCR). Finally, PI-PLCbeta1 gene and protein expression
      were assessed by both real-time PCR and immunocytochemical experiments. RESULTS:
      Collectively, 35 (43.75%) of 80 of the MDS patients showed a specific mono
      allelic deletion of PI-PLCbeta1. Kaplan-Meier analysis revealed a significant
      association (P < .0001) between the PI-PLCbeta1 mono-allelic deletion and a
      higher risk of evolution into acute myeloid leukemia (AML), since 23 of 35 MDS
      patients (65.7%) bearing the PI-PLCbeta1 mono-allelic deletion evolved into AML.
      Even in multivariate analysis, the PI-PLCbeta1 mono-allelic deletion retained a
      higher significance, with a P < .001, as a prognostic factor of evolution into
      AML (odds ratio [OR] 1.83; 95% CI, 2.26 to 17.24; P = .00045). Finally, PI
      PLCbeta1 deletion was related to an altered gene and protein expression.
      CONCLUSION: PI-PLCbeta1 mono-allelic deletion is associated with a worse clinical
      outcome in MDS patients, hinting at the identification of a new group at higher
      risk of AML evolution and representing a reliable prognostic tool. Moreover,
      targeting PI-PLCbeta1 pathways might emerge as a new therapeutic strategy for
      MDS.

PMID- 19114694
TI  - Short delay in initiation of radiotherapy may not affect outcome of patients with
      glioblastoma: a secondary analysis from the radiation therapy oncology group
      database.
AB  - PURPOSE: To analyze the Radiation Therapy Oncology Group (RTOG) database of
      patients with glioblastoma and appraise whether outcome was influenced by time to
      initiation of radiation therapy (RT). PATIENTS AND METHODS: From 1974 through
      2003, adult patients with histologically confirmed supratentorial glioblastoma
      were enrolled onto 16 RTOG studies. Of 3,052 enrolled patients, 197 patients (6%)
      were either initially rendered ineligible or had insufficient chronologic data,
      leaving a cohort of 2,855 patients for the present analysis. We selected four
      patient groups based on the interval from surgery to the start of RT: <or= 2
      weeks, 2 to 3 weeks, 3 to 4 weeks, more than 4 weeks to the protocol eligibility
      limit of 6 weeks. Survival times were estimated by the Kaplan-Meier method.
      Multivariate analysis incorporated variables of time interval, recursive
      partitioning analysis (RPA) class, and treatment regimen. RESULTS: No decrement
      in survival could be identified with increasing time to initiation of RT. Among
      our four temporal groupings, median survival time was unexpectedly and
      significantly greater in the group with the longest interval (> 4 weeks) than in
      those with the shortest delay (<or= 2 weeks): respectively, 12.5 months versus
      9.2 months (P < .0001). On multivariate analysis, with overall survival as the
      end point, time interval more than 4 weeks and lower RPA class were both
      significant predictors of improved outcome. Treatment regimen was not a
      significant factor. CONCLUSION: There is no evident reduction in survival by
      delaying initiation of RT within the relatively narrow constraint of 6 weeks. An
      unanticipated yet significantly superior outcome was identified for patients for
      whom RT was delayed beyond 4 weeks from surgery.

PMID- 19114695
TI  - Medication errors among adults and children with cancer in the outpatient
      setting.
AB  - PURPOSE: Outpatients with cancer receive complicated medication regimens in the
      clinic and home. Medication errors in this setting are not well described. We
      aimed to determine rates and types of medication errors and systems factors
      associated with error in outpatients with cancer. METHODS: We retrospectively
      reviewed records from visits to three adult and one pediatric oncology clinic in
      the Southeast, Southwest, Northeast, and Northwest for medication errors using
      established methods. Two physicians independently judged whether an error
      occurred (kappa = 0.65), identified its severity (kappa = 0.76), and listed
      possible interventions. RESULTS: Of 1,262 adult patient visits involving 10,995
      medications, 7.1% (n = 90; 95% CI, 5.7% to 8.6%) were associated with a
      medication error. Of 117 pediatric visits involving 913 medications, 18.8% (n =
      22; 95% CI, 12.5% to 26.9%) were associated with a medication error. Among all
      visits, 64 of the 112 errors had the potential to cause harm, and 15 errors
      resulted in injury. There was a range in the rates of chemotherapy errors (0.3 to
      5.8 per 100 visits) and home medication errors (0 to 14.5 per 100 visits in
      children) at different sites. Errors most commonly occurred in administration
      (56%). Administration errors were often due to confusion over two sets of orders,
      one written at diagnosis and another adjusted dose on the day of administration.
      Physician reviewers selected improved communication most often to prevent error.
      CONCLUSION: Medication error rates are high among adult and pediatric outpatients
      with cancer. Our findings suggest some practical targets for intervention,
      including improved communication about medication administration in the clinic
      and home.

PMID- 19114696
TI  - Second cancers after squamous cell carcinoma and adenocarcinoma of the cervix.
AB  - PURPOSE: Although cervical squamous cell carcinoma (SCC) and adenocarcinoma (AC)
      are both caused by human papillomavirus (HPV) infection, they differ in cofactors
      such as cigarette smoking. We assessed whether these cofactor differences
      translate into differences in second cancer risk. PATIENTS AND METHODS: We
      assessed second cancer risk among 85,109 cervical SCC and 10,280 AC survivors
      reported to population-based cancer registries in Denmark, Finland, Norway,
      Sweden, and the United States. Risks compared to the general population were
      assessed using standardized incidence ratios (SIR). RESULTS: Overall cancer risk
      was significantly increased among both cervical SCC survivors (n = 10,559 second
      cancers; SIR, 1.31; 95% CI, 1.29 to 1.34) and AC survivors (n = 920 second
      cancers; SIR, 1.29; 95% CI, 1.22 to 1.38). Risks of HPV-related and radiation
      related cancers were increased to a similar extent among cervical SCC and AC
      survivors. Although significantly increased in both groups when compared with the
      general population, risk of smoking-related cancers was significantly higher
      among cervical SCC than AC survivors (P = .015; SIR for cervical SCC = 2.07 v AC
      = 1.78). This difference was limited to lung cancer (SIR for cervical SCC = 2.69
      v AC = 2.18; P = .026). The increased lung cancer risk among cervical AC
      survivors was observed for both lung SCC and lung AC. SIRs for second cancers of
      the colon, soft tissue, melanoma, and non-Hodgkin's lymphoma were significantly
      higher among cervical AC than SCC survivors. CONCLUSION: The second cancer
      profiles among cervical SCC and AC survivors mirror the similarities and
      differences in cofactors for these two histologies. Because smoking is not a
      cofactor for cervical AC, the increased lung cancer risk suggests a role for
      additional factors.

PMID- 19114697
TI  - Sentinel lymph node biopsy after neoadjuvant chemotherapy for advanced breast
      cancer: results of Ganglion Sentinelle et Chimiotherapie Neoadjuvante, a French
      prospective multicentric study.
AB  - PURPOSE: To determine the detection rate, the false-negative rate, and the
      accuracy of sentinel lymph node (SLN) detection after neoadjuvant chemotherapy
      (NAC) for advanced breast cancer. PATIENTS AND METHODS: A prospective
      multicentric study was initiated to evaluate the results of SLN biopsy with the
      combined method after NAC for advanced large operable breast cancer. RESULTS:
      From September 2003 to March 2007, 195 patients enrolled from 12 institutions
      were found suitable for evaluation. The detection rate was 90% (176 of 195
      patients), and the false-negative rate was 11.5% (six of 52 patients). Patients
      without axillary palpable nodes (N0) before NAC had a better detection rate
      compared with patients with axillary suspicious nodes (N1, 94.6% v 81.5%; P =
      .008). The false-negative rate was not correlated with clinical nodal status
      before NAC (9.4% v 15%; P = .66). CONCLUSION: This study confirms the feasibility
      of SLN biopsy after NAC in the case of large operable breast cancer. The
      detection rate, false-negative rate, and accuracy do not differ from those
      obtained in the case of early breast cancer without NAC, thus demonstrating the
      feasibility of SLN biopsy after NAC.

PMID- 19114699
TI  - Other malignancies in chronic lymphocytic leukemia/small lymphocytic lymphoma.
AB  - PURPOSE: Other malignancies have been reported to occur with increased frequency
      in chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL). The aim of
      this study was to determine the frequency, outcomes, and factors associated with
      other cancers in patients with CLL/SLL. PATIENTS AND METHODS: We reviewed the
      records of consecutive patients with previously untreated CLL/SLL seen at The
      University of Texas M. D. Anderson Cancer Center from 1985 to 2005. The number of
      second cancers observed was compared with the number expected from the
      Surveillance, Epidemiology, and End Results database. RESULTS: Among 2,028
      patients, 324 (16%) had a history of other cancers and 227 (11.2%) developed
      other malignancies during the follow-up period. Overall, 625 cancers were
      observed in 551 patients, including skin (30%), prostate (13%), breast (9%),
      melanoma (8%), lymphoma (8%), gastrointestinal (9%), lung (6%), and other cancers
      (17%). The risk of a second cancer was 2.2 times higher than the expected risk.
      The response rates in patients with and without a history of other cancers were
      86% and 92%, respectively (P = .04), and the 5-year survival rates were 70% and
      82%, respectively (P < .001). In Cox analysis, independent factors predicting
      development of new cancers were older age, male sex, and elevated levels of beta2
      microglobulin, lactate dehydrogenase, and creatinine. In patients who were
      treated for CLL/SLL, the treatment regimen did not affect the risk of subsequent
      cancer (P = .49). CONCLUSION: Patients with CLL/SLL have more than twice the risk
      of developing a second cancer and an increased frequency of certain cancer types.
      Awareness of risk factors could permit early detection.

PMID- 19114698
TI  - The terrible choice: re-evaluating hospice eligibility criteria for cancer.
AB  - PURPOSE: To be eligible for the Medicare Hospice Benefit, cancer patients with a
      life expectancy of 6 months or less must give up curative treatment. Our goal was
      to determine whether willingness to make this choice identifies patients with
      greater need for hospice services. PATIENTS AND METHODS: Three hundred patients
      with cancer and 171 family members were recruited from six oncology practices.
      Respondents completed conjoint interviews in which their perceived need for five
      hospice services was calculated from the choices they made among combinations of
      services. Patients' preferences for treatment were measured, and patients were
      followed for 6 months or until death. RESULTS: Thirty-eight patients (13%) said
      they would not want cancer treatment even if it offered an almost 100% chance of
      6-month survival. These patients, who would have been eligible for hospice, did
      not have greater perceived need for hospice services compared with other patients
      (n = 262; mean, 1.75 v 1.98; Wilcoxon rank sum test, P = .46), nor did their
      family members (mean, 1.95 v 2.04; Wilcoxon rank sum test, P = .80). Instead,
      independent predictors of patients' perceived need for hospice services included
      African American ethnicity, less social support, worse functional status, and a
      greater burden of psychological symptoms. For families, predictors included
      caregiver burden, worse self-reported health, working outside the home, and
      caring for a patient with worse functional status. CONCLUSION: The requirement
      that patients forgo life-sustaining treatment does not identify patients with
      greater perceived need for hospice services. Other characteristics offer a better
      way to identify the patients who are most likely to benefit from hospice.

PMID- 19114700
TI  - Validation of a colorectal cancer risk prediction model among white patients age
      50 years and older.
AB  - PURPOSE: Validation of an absolute risk prediction model for colorectal cancer
      (CRC) by using a large, population-based cohort. PATIENTS AND METHODS: The
      National Institutes of Health (NIH) -American Association of Retired Persons
      (AARP) diet and health study, a prospective cohort study, was used to validate
      the model. Men and women age 50 to 71 years at baseline answered self
      administered questionnaires that asked about demographic characteristics, diet,
      lifestyle, and medical histories. We compared expected numbers of CRC patient
      cases predicted by the model to the observed numbers of CRC patient cases
      identified in the NIH-AARP study overall and in subgroups defined by risk factor
      combinations. The discriminatory power was measured by the area under the
      receiver-operating characteristic curve (AUC). RESULTS: During an average of 6.9
      years of follow-up, we identified 2,092 and 832 incident CRC patient cases in men
      and women, respectively. The overall expected/observed ratio was 0.99 (95% CI,
      0.95 to 1.04) in men and 1.05 (95% CI, 0.98 to 1.11) in women. Agreement between
      the expected and the observed number of cases was good in most risk factor
      categories, except for in subgroups defined by CRC screening and polyp history.
      This discrepancy may be caused by differences in the question on screening and
      polyp history between two studies. The AUC was 0.61 (95% CI, 0.60 to 0.62) for
      men and 0.61 (95% CI, 0.59 to 0.62) for women, which was similar to other risk
      prediction models. CONCLUSION: The absolute risk model for CRC was well
      calibrated in a large prospective cohort study. This prediction model, which
      estimates an individual's risk of CRC given age and risk factors, may be a useful
      tool for physicians, researchers, and policy makers.

PMID- 19114702
TI  - Immunoglobulin prophylaxis in hematopoietic stem cell transplantation: systematic
      review and meta-analysis.
AB  - PURPOSE: Because the role of immunoglobulins (IVIG) prophylaxis in patients
      undergoing hematopoietic stem-cell transplantation (HSCT) has not been
      established in terms of survival and infection prevention, we conducted a meta
      analysis evaluating these issues. METHODS: Systematic review and meta-analysis of
      randomized-controlled trials comparing prophylaxis with polyvalent IVIG or
      cytomegalovirus (CMV)-IVIG and control or another preparation or dose. PUBMED,
      Cochrane Library, LILACS, and conference proceedings were searched. Two reviewers
      appraised the quality of trials and extracted data. Relative risks (RRs) with 95%
      CIs were estimated and pooled. RESULTS: Thirty trials including 4,223 patients
      undergoing bone marrow transplantation (BMT) were included. There was no
      difference in all-cause mortality when polyvalent IVIG or CMV-IVIG was compared
      to control (RR, 0.99; 95% CI, 0.88 to 1.12; and RR, 0.86; 95% CI, 0.63 to 1.16,
      respectively). There was no difference in clinically documented infections when
      polyvalent IVIG was compared with control (RR, 1.00; 95% CI, 0.90 to 1.10; five
      trials). CMV infections were not significantly reduced with either polyvalent
      IVIG or CMV-IVIG. Interstitial pneumonitis was reduced with polyvalent IVIG in
      older studies but not in the more recent ones, nor in studies assessing CMV-IVIG.
      Polyvalent IVIG increased the risk for veno-occlusive disease (RR, 2.73; (95% CI,
      1.11 to 6.71). Graft-versus-host disease was not affected. CONCLUSION: Because
      there is no advantage in terms of survival or infection prevention, IVIG does not
      have a role in HSCT.

PMID- 19114701
TI  - Colorectal cancer risk prediction tool for white men and women without known
      susceptibility.
AB  - PURPOSE: Given the high incidence of colorectal cancer (CRC), and the
      availability of procedures that can detect disease and remove precancerous
      lesions, there is a need for a model that estimates the probability of developing
      CRC across various age intervals and risk factor profiles. METHODS: The
      development of separate CRC absolute risk models for men and women included
      estimating relative risks and attributable risk parameters from population-based
      case-control data separately for proximal, distal, and rectal cancer and
      combining these estimates with baseline age-specific cancer hazard rates based on
      Surveillance, Epidemiology, and End Results (SEER) incidence rates and competing
      mortality risks. RESULTS: For men, the model included a cancer-negative
      sigmoidoscopy/colonoscopy in the last 10 years, polyp history in the last 10
      years, history of CRC in first-degree relatives, aspirin and nonsteroidal anti
      inflammatory drug (NSAID) use, cigarette smoking, body mass index (BMI), current
      leisure-time vigorous activity, and vegetable consumption. For women, the model
      included sigmoidoscopy/colonoscopy, polyp history, history of CRC in first-degree
      relatives, aspirin and NSAID use, BMI, leisure-time vigorous activity, vegetable
      consumption, hormone-replacement therapy (HRT), and estrogen exposure on the
      basis of menopausal status. For men and women, relative risks differed slightly
      by tumor site. A validation study in independent data indicates that the models
      for men and women are well calibrated. CONCLUSION: We developed absolute risk
      prediction models for CRC from population-based data, and a simple questionnaire
      suitable for self-administration. This model is potentially useful for
      counseling, for designing research intervention studies, and for other
      applications.

PMID- 19114703
TI  - Can women with early-stage breast cancer make an informed decision for
      mastectomy?
AB  - PURPOSE: The purpose of this study was to measure the degree to which informed
      women chose mastectomy, and to reveal their reasons for this choice. PATIENTS AND
      METHODS: This was a prospective cohort study of patients radiographically and
      pathologically eligible for either mastectomy or breast-conserving surgery (BCS;
      n = 125). Participants completed questionnaires at three time points: baseline,
      after viewing a decision aid, and after a surgical consultation. Questionnaires
      assessed clinical history, preference for participation in decision making,
      information comprehension, values, decisional conflict, and preferred treatment.
      RESULTS: Of 125 participants, 44 (35%) chose mastectomy. Most understood that BCS
      and mastectomy offer an equivalent survival benefit (98%) and that BCS has a
      slightly higher local recurrence risk (63%); most accurately identified the
      magnitude of ipsilateral local recurrence risk (91%). Values assigned to three
      treatment attributes/outcomes ("remove breast for peace of mind," "avoid
      radiation," and "keep breast") clearly discriminated between patients choosing
      mastectomy or BCS. High decisional conflict scores improved after both the
      decision aid and surgical consultation. CONCLUSION: Although conventional wisdom
      may view BCS as the preferred treatment, a notable proportion of well informed
      women choose mastectomy. Whereas prior studies have linked objective factors to
      treatment choice, this study reveals subjective preferences that underlie
      decision making. The systematic use of a decision aid before the surgical
      consultation may help women make informed, values-based decisions, while clearly
      reducing decisional conflict.

PMID- 19114704
TI  - Phase II trial of single-agent bevacizumab followed by bevacizumab plus
      irinotecan at tumor progression in recurrent glioblastoma.
AB  - PURPOSE: To evaluate single-agent activity of bevacizumab in patients with
      recurrent glioblastoma. PATIENTS AND METHODS: Patients with recurrent
      glioblastoma were treated with bevacizumab 10 mg/kg every 2 weeks. After tumor
      progression, patients were immediately treated with bevacizumab in combination
      with irinotecan 340 mg/m(2) or 125 mg/m(2) every 2 weeks, depending on use of
      enzyme-inducing antiepileptic drugs. Complete patient evaluations were repeated
      every 4 weeks. RESULTS: Forty-eight heavily pretreated patients were accrued to
      this study. Thromboembolic events (12.5%), hypertension (12.5%), hypophosphatemia
      (6%), and thrombocytopenia (6%) were the most common drug-associated adverse
      events. Six patients (12.5%) were removed from study for drug-associated toxicity
      (five thromboembolic events, one bowel perforation). Thirty-four patients (71%)
      and 17 patients (35%) achieved radiographic response based on Levin and Macdonald
      criteria, respectively. Median progression-free survival (PFS) was 16 weeks (95%
      CI, 12 to 26 weeks). The 6-month PFS was 29% (95% CI, 18% to 48%). The 6-month
      overall survival was 57% (95% CI, 44% to 75%). Median overall survival was 31
      weeks (95% CI, 21 to 54 weeks). Early magnetic resonance imaging response (first
      96 hours and 4 weeks) was predictive of long-term PFS, with the Levin criteria
      being more predictive than Macdonald criteria. Of 19 patients treated with
      bevacizumab plus irinotecan at progression, there were no objective radiographic
      responses. Eighteen patients (95%) experienced disease progression by the second
      cycle, and the median PFS was 30 days. CONCLUSION: We conclude that single-agent
      bevacizumab has significant biologic and antiglioma activity in patients with
      recurrent glioblastoma.

PMID- 19114706
TI  - Predictors of referral for specialized psychosocial oncology care in patients
      with metastatic cancer: the contributions of age, distress, and marital status.
AB  - PURPOSE: This study examines the rate and prediction of referral for specialized
      psychosocial oncology care in 326 patients with metastatic GI or lung cancer.
      PATIENTS AND METHODS: Referral information was abstracted from medical records
      and hospital databases. Patients completed measures of psychosocial and physical
      distress and functioning. RESULTS: Routine referral occurred in 33% of patients,
      and in 42% and 44%, respectively, of those scoring high on measures of depression
      (Beck Depression Inventory [BDI]-II >or= 15) and hopelessness (Beck Hopelessness
      Scale >or= 8). Univariate analyses indicated that referral was associated with
      younger age, unmarried status, living alone, presence of more depressive
      symptoms, hopelessness, and attachment anxiety, and with less social support,
      self-esteem, and spiritual well-being (all P < .05). Among the significantly
      depressed (BDI-II >or= 15), 100% of those less than 40 years of age, but only 22%
      of those age 70 years or older were referred. Multivariate analyses indicated
      that referral was associated with younger age, unmarried status, and presence of
      more depressive symptoms. Moreover, increasing age was associated with a
      progressively lower likelihood of referral independent of the level of distress.
      CONCLUSION: Routine referral of patients with metastatic cancer for psychosocial
      oncology care was predicted by presence of more severe depressive symptoms,
      younger age, and unmarried status. The rate of referral progressively declined
      with each decade of age, even among those with significant distress. These
      findings are consistent with some aspects of Andersen's model of health care
      utilization. The extent to which referred patients represent those who are most
      likely to benefit deserves further investigation.

PMID- 19114705
TI  - Behavioral health services for women who have breast cancer.
AB  - PURPOSE: To explore whether the use of behavioral health services (BHS) among
      women with breast cancer is influenced by how insurance plans administer these
      services, we compared utilization of psychotherapy and psychotherapeutic
      medications among women with breast cancer who received BHS coverage through a
      carve-out versus integrated arrangement. PATIENTS AND METHODS: We analyzed
      insurance claims, enrollment data, and benefit design data from the MarketScan
      Commercial Claims & Encounters Research Database for the years 1998 to 2002 for
      women <or= 63 years old with newly diagnosed breast cancer. We compared the
      probability of receiving psychotherapy, the likelihood of receiving
      antidepressant/antianxiety/hypnotic medications, and the number of psychotherapy
      sessions used during the year after a breast cancer diagnosis among women whose
      behavioral health services were provided through carve-out versus integrated
      arrangements. RESULTS: Women enrolled in carve-outs were significantly less
      likely to receive any psychotherapy visits compared with women in integrated
      arrangements (odds ratio, 0.68; P < .01). Conditional on having received
      psychotherapy, however, women in carve-out arrangements used more psychotherapy
      visits than women in integrated arrangements. The use of antianxiety/hypnotic
      drugs was significantly higher for women in carve-out arrangements versus women
      in integrated arrangements (36.1% v 32.6%, P < .05). Moreover, women who received
      psychotherapy were significantly more likely to received antidepressants and
      antianxiety/hypnotic medications (five and three times more likely,
      respectively). CONCLUSION: The type of BHS arrangement was associated with the
      utilization of psychotherapy and psychotherapeutic medications among women with
      breast cancer.

PMID- 19114707
TI  - Triglyceride synthesis in epididymal adipose tissue: contribution of glucose and
      non-glucose carbon sources.
AB  - The obesity epidemic has generated interest in determining the contribution of
      various pathways to triglyceride synthesis, including an elucidation of the
      origin of triglyceride fatty acids and triglyceride glycerol. We hypothesized
      that a dietary intervention would demonstrate the importance of using glucose
      versus non-glucose carbon sources to synthesize triglycerides in white adipose
      tissue. C57BL/6J mice were fed either a low fat, high carbohydrate (HC) diet or a
      high fat, carbohydrate-free (CF) diet and maintained on 2H2O (to determine total
      triglyceride dynamics) or infused with [6,6-(2)H]glucose (to quantify the
      contribution of glucose to triglyceride glycerol). The 2H2O labeling data
      demonstrate that although de novo lipogenesis contributed approximately 80%
      versus approximately 5% to the pool of triglyceride palmitate in HC- versus CF
      fed mice, the epididymal adipose tissue synthesized approximately 1.5-fold more
      triglyceride in CF- versus HC-fed mice, i.e. 37+/-5 versus 25+/-3 micromolxday(
      1). The [6,6-(2)H]glucose labeling data demonstrate that approximately 69 and
      approximately 28% of triglyceride glycerol is synthesized from glucose in HC-
      versus CF-fed mice, respectively. Although these data are consistent with the
      notion that non-glucose carbon sources (e.g. glyceroneogenesis) can make
      substantial contributions to the synthesis of triglyceride glycerol (i.e. the
      absolute synthesis of triglyceride glycerol from non-glucose substrates increased
      from approximately 8 to approximately 26 micromolxday(-1) in HC- versus CF-fed
      mice), these observations suggest (i) the importance of nutritional status in
      affecting flux rates and (ii) the operation of a glycerol-glucose cycle.

PMID- 19114708
TI  - RNA sequence and two-dimensional structure features required for efficient
      substrate modification by the Saccharomyces cerevisiae RNA:{Psi}-synthase Pus7p.
AB  - The RNA:pseudouridine (Psi) synthase Pus7p of Saccharomyces cerevisiae is a
      multisite-specific enzyme that is able to modify U(13) in several yeast tRNAs,
      U(35) in the pre-tRNA(Tyr) (GPsiA), U(35) in U2 small nuclear RNA, and U(50) in 5
      S rRNA. Pus7p belongs to the universally conserved TruD-like family of RNA:Psi
      synthases found in bacteria, archaea, and eukarya. Although several RNA
      substrates for yeast Pus7p have been identified, specificity of their recognition
      and modification has not been studied. However, conservation of a 7-nt-long
      sequence, including the modified U residue, in all natural Pus7p substrates
      suggested the importance of these nucleotides for Pus7p recognition and/or
      catalysis. Using site-directed mutagenesis, we designed a set of RNA variants
      derived from the yeast tRNA(Asp)(GUC), pre-tRNA(Tyr)(GPsiA), and U2 small nuclear
      RNA and tested their ability to be modified by Pus7p in vitro. We demonstrated
      that the highly conserved U(-2) and A(+1) residues (nucleotide numbers refer to
      target U(0)) are crucial identity elements for efficient modification by Pus7p.
      Nucleotide substitutions at other surrounding positions (-4, -3, +2, +3) have
      only a moderate effect. Surprisingly, the identity of the nucleotide immediately
      5' to the target U(0) residue (position -1) is not important for efficient
      modification. Alteration of tRNA three-dimensional structure had no detectable
      effect on Pus7p activity at position 13. However, our results suggest that the
      presence of at least one stem-loop structure including or close to the target U
      nucleotide is required for Pus7p-catalyzed modification.

PMID- 19114709
TI  - Structure of the capsular polysaccharide of pneumococcal serotype 11A reveals a
      novel acetylglycerol that is the structural basis for 11A subtypes.
AB  - We have undertaken a structural assessment of Streptococcus pneumoniae 11A
      polysaccharide as well as two clinical isolates related to 11A. The clinical
      isolates were labeled 11Aalpha and 11Abeta. The result of our experiments is a
      revision to the old structure for S. pneumoniae 11A polysaccharide. The new
      structure differs from the old structure in both the primary connectivities and
      acetylation pattern. We also show that 11A contains an acetylglycerol-PO4 moiety,
      a substitution that is heretofore unknown in the bacterial polysaccharide
      literature. The two clinical isolates were also structurally characterized.
      11Aalpha was determined to be identical to 11A. 11Abeta is a new serotype, which
      differs from 11A in the absence of the acetylation of the glycerol-PO4 moiety and
      a different acetylation pattern of the saccharides. Thus, we propose that the
      acetylglycerol is the structural basis for 11Aalpha and 11Abeta subtypes.

PMID- 19114710
TI  - The binding properties of minimal oligosaccharides reveal a common heparan
      sulfate/dermatan sulfate-binding site in hepatocyte growth factor/scatter factor
      that can accommodate a wide variety of sulfation patterns.
AB  - Heparan sulfate (HS)/heparin and dermatan sulfate (DS) both bind with high
      affinity to hepatocyte growth factor/scatter factor (HGF/SF) and function as
      necessary co-factors in vitro. How both these two structurally distinct
      glycosaminoglycans (GAGs) are recognized has remained unclear. We have now
      reconciled this issue using a panel of minimal tri- and tetrasaccharide sequences
      of variable but well defined sulfation patterns in combination with further
      development of the gel mobility shift assay to allow simultaneous comparisons of
      relative protein affinities/selectivities for different oligosaccharides. From
      this approach it would seem that a minimum binding sequence is a disulfated
      trisaccharide comprised of an internal iduronate flanked by monosulfated
      hexosamine residues and that additional sulfation further enhances affinity.
      However, the similarity in recognition of HS/heparin and DS seems to arise
      primarily from a lack of any apparent positional requirement for sulfation. Thus,
      isomers of HS/heparin tetrasaccharides containing only two sulfates irrespective
      of whether they are purely N-, 2-O-, or 6-O-sulfates bind with equivalent
      apparent affinity as a disulfated DS tetrasaccharide. In addition, the NMR
      chemical shifts induced in NK1 (the truncated variant of HGF/SF comprised of the
      N-terminal and first Kringle domains) by titration with either heparin or DS
      oligosaccharides strongly indicate that both bind to essentially the same site.
      Together, these observations reveal an unexpected degree of flexibility in the
      GAG-HGF/SF interface, allowing a single binding site in the protein to
      accommodate iduronate-containing sequences of variable sulfation pattern and/or
      density from different GAGs.

PMID- 19114711
TI  - Substrate requirements for SPPL2b-dependent regulated intramembrane proteolysis.
AB  - Intramembrane proteolysis is now widely recognized as an important physiological
      pathway required for reverse signaling and membrane protein degradation. Aspartyl
      intramembrane cleaving proteases of the GXGD-type play an important regulatory
      role in health and disease. Besides gamma-secretase/presenilin, signal peptide
      peptidase (SPP) and SPP-like (SPPL) peptidases also belong to the family of GXGD
      type aspartyl proteases. Although recently the first SPPL2a/b substrates have
      been identified, very little is known about substrate requirements, which allow
      them to be efficiently processed within the membrane. We demonstrate that similar
      to gamma-secretase substrates, intramembrane proteolysis of Bri2 (Itm2b) is
      greatly facilitated by an initial shedding event mediated by ADAM-10. Serial
      deletions revealed that the length of the ectodomain negatively correlates with
      efficient intramembrane proteolysis. Bri3 (Itm2c), which is highly homologous to
      Bri2, fails to be shed. Failure of shedding of Bri3 is accompanied by a lack of
      intramembrane proteolysis by SPPL2b. Surprisingly, a low molecular weight
      membrane-retained stub of Bri3 also fails to be processed by SPPL2b, indicating
      that shedding per se is not sufficient for subsequent intramembrane proteolysis.
      Extensive domain swapping analysis reveals that primary sequence determinants
      within the intracellular domain and the transmembrane domain together with short
      luminal juxtamembrane sequences are required for efficient intramembrane
      proteolysis.

PMID- 19114712
TI  - HspB8 participates in protein quality control by a non-chaperone-like mechanism
      that requires eIF2{alpha} phosphorylation.
AB  - Aggregation of mutated proteins is a hallmark of many neurodegenerative
      disorders, including Huntington disease. We previously reported that
      overexpression of the HspB8.Bag3 chaperone complex suppresses mutated huntingtin
      aggregation via autophagy. Classically, HspB proteins are thought to act as ATP
      independent molecular chaperones that can bind unfolded proteins and facilitate
      their processing via the help of ATP-dependent chaperones such as the Hsp70
      machine, in which Bag3 may act as a molecular link between HspB, Hsp70, and the
      ubiquitin ligases. However, here we show that HspB8 and Bag3 act in a non
      canonical manner unrelated to the classical chaperone model. Rather, HspB8 and
      Bag3 induce the phosphorylation of the alpha-subunit of the translation initiator
      factor eIF2, which in turn causes a translational shut-down and stimulates
      autophagy. This function of HspB8.Bag3 does not require Hsp70 and also targets
      fully folded substrates. HspB8.Bag3 activity was independent of the endoplasmic
      reticulum (ER) stress kinase PERK, demonstrating that its action is unrelated to
      ER stress and suggesting that it activates stress-mediated translational arrest
      and autophagy through a novel pathway.

PMID- 19114713
TI  - Basic residues are critical to the activity of peptide inhibitors of human T cell
      leukemia virus type 1 entry.
AB  - A synthetic peptide based on the leash and alpha-helical region (LHR) of human T
      cell leukemia virus type 1 envelope is a potent inhibitor of viral entry into
      cells. The inhibitory peptide targets a triple-stranded coiled-coil motif of the
      fusion-active transmembrane glycoprotein and in a trans-dominant negative manner
      blocks resolution to the trimer-of-hairpins form. The LHR-mimetic is, therefore,
      functionally analogous to the C34/T20-type inhibitors of human immunodeficiency
      virus. Previous attempts to shorten the bioactive peptide produced peptides with
      severely attenuated activity. We now demonstrate that truncated peptides often
      suffer from poor solubility and impaired coiled coil binding properties, and we
      identify features that are critical to peptide function. In particular, the alpha
      helical region of the LHR-mimetic is necessary but not sufficient for inhibitory
      activity. Moreover, two basic residues are crucial for coiled-coil binding and
      efficient inhibition of membrane fusion. By retaining these basic residues and a
      region of main chain peptide contacts with the coiled coil, a core LHR-mimetic
      was obtained that retains both the inhibitory properties and solubility profile
      of the parental peptide. Variants of the core peptide inhibit both membrane
      fusion and infection of cells by free viral particles, but unexpectedly,
      infection by virions was more susceptible to inhibition by low activity
      inhibitors than syncytium formation. The core inhibitor provides a valuable lead
      in the search for smaller more bio-available peptides and peptido-mimetics that
      possess anti-viral activity. Such molecules may be attractive candidates for
      therapeutic intervention in human T cell leukemia virus type 1 infections.

PMID- 19114714
TI  - LQT1-associated mutations increase KCNQ1 proteasomal degradation independently of
      Derlin-1.
AB  - Mutations in the potassium channel KCNQ1 that determine retention of the mutated
      proteins in the endoplasmic reticulum (ER) are associated with the autosomal
      dominant negative Romano-Ward LQT1 cardiac syndrome. In the present study, we
      have analyzed the consequences and the potential molecular mechanisms involved in
      the ER retention of three Romano-Ward mutations located in KCNQ1 N terminus
      (Y111C, L114P, and P117L). We showed that the mutant KCNQ1 proteins exhibited
      reduced expression levels with respect to wild-type (WT)-KCNQ1. Radiolabeling
      pulse-chase experiments revealed that the lower expression levels did not result
      from reduced rate of synthesis. Instead, using a combination of Western blot and
      pulse-chase experiments, we showed that the mutant channel Y111C-KCNQ1, used as a
      model, was ubiquitinated and degraded in the proteasome more rapidly (t((1/2)) =
      82 min) than WT-KCNQ1 channel (t((1/2)) = 113 min). On the other hand, KCNQ1
      degradation did not appear to involve the GTP-dependent pathway. We also showed
      that KCNE1 stabilized both wild-type and Y111C proteins. To identify potential
      actors involved in KCNQ1 degradation, we studied the implication of the ER
      resident protein Derlin-1 in KCNQ1 degradation. We showed that although KCNQ1 and
      Derlin-1 share the same molecular complex and co-immunoprecipitate when co
      expressed in HEK293FT cells, Derlin-1 did not affect KCNQ1 steady state
      expression and degradation. These data were confirmed in T84 cells that express
      endogenous KCNQ1 and Derlin-1. Small interfering RNA knock-down of Derlin-1 did
      not modify KCNQ1 expression level, and no interaction between endogenous KCNQ1
      and Derlin-1 could be detected.

PMID- 19114716
TI  - Comment on: Barker et al. (2008) Two single nucleotide polymorphisms identify the
      highest-risk diabetes HLA genotype: Diabetes 57:3152-3155, 2008.

PMID- 19114715
TI  - MILI, a PIWI-interacting RNA-binding protein, is required for germ line stem cell
      self-renewal and appears to positively regulate translation.
AB  - The Argonaute/PIWI protein family consists of Argonaute and PIWI subfamilies.
      Argonautes function in RNA interference and micro-RNA pathways; whereas PIWIs
      bind to PIWI-interacting RNAs and regulate germ line development, stem cell
      maintenance, epigenetic regulation, and transposition. However, the role of PIWIs
      in mammalian stem cells has not been demonstrated, and molecular mechanisms
      mediated by PIWIs remain elusive. Here we show that MILI, a murine PIWI protein,
      is expressed in the cytoplasm of testicular germ line stem cells, spermatogonia,
      and early spermatocytes, where it is enriched in chromatoid bodies. MILI is
      essential for the self-renewing division and differentiation of germ line stem
      cells but does not affect initial establishment of the germ line stem cell
      population at 7 days postpartum. Furthermore, MILI forms a stable RNA-independent
      complex with eIF3a and associates with the eIF4E- and eIF4G-containing m7G cap
      binding complex. In isolated 7 days postpartum seminiferous tubules containing
      mostly germ line stem cells, the mili mutation has no effect on the cellular mRNA
      level yet significantly reduces the rate of protein synthesis. These observations
      indicate that MILI may positively regulate translation and that such regulation
      is required for germ line stem cell self-renewal.

PMID- 19114718
TI  - Comment on: Kloting et al. (2008) Autocrine IGF-1 action in adipocytes controls
      systemic IGF-1 concentrations and growth: Diabetes 57:2074-2082.

PMID- 19114720
TI  - ADA research funding in 2009: where will we be?

PMID- 19114721
TI  - Can we learn from viruses how to prevent type 1 diabetes?: the role of viral
      infections in the pathogenesis of type 1 diabetes and the development of novel
      combination therapies.
AB  - We will take a journey from basic pathogenetic mechanisms elicited by viral
      infections that play a role in the development of type 1 diabetes to clinical
      interventions, where we will discuss novel combination therapies. The role of
      viral infections in the development of type 1 diabetes is a rather interesting
      topic because in experimental models viruses appear capable of both accelerating
      as well as decelerating the immunological processes leading to type 1 diabetes.
      Consequently, I will discuss some of the underlying mechanisms for each situation
      and consider methods to investigate the proposed dichotomy for the involvement of
      viruses in human type 1 diabetes. Prevention of type 1 diabetes by infection
      supports the so-called "hygiene hypothesis." Interestingly, viruses invoke
      mechanisms that need to be exploited by novel combinatorial immune-based
      interventions, the first one being the elimination of autoaggressive T-cells
      attacking the beta-cells, ultimately leading to their immediate but temporally
      limited amelioration. The other is the invigoration of regulatory T-cells
      (Tregs), which can mediate long-term tolerance to beta-cell proteins in the
      pancreatic islets and draining lymph nodes. In combination, these two immune
      elements have the potential to permanently stop type 1 diabetes. It is my belief
      that only combination therapies will enable the permanent prevention and curing
      of type 1 diabetes.

PMID- 19114722
TI  - Role of plasmacytoid dendritic cells in type 1 diabetes: friend or foe?

PMID- 19114723
TI  - Selective inhibitors of 11beta-hydroxysteroid dehydrogenase type 1 for patients
      with metabolic syndrome: is the target liver, fat, or both?

PMID- 19114724
TI  - Fat partitioning and insulin sensitivity: robbing Peter to pay Paul?

PMID- 19114725
TI  - Targeting hepatic glucokinase in type 2 diabetes: weighing the benefits and
      risks.

PMID- 19114726
TI  - Hypoglycemic detection at the portal vein: absent in humans or yet to be
      elucidated?

PMID- 19114727
TI  - Taking a daily vitamin to prevent type 1 diabetes?

PMID- 19114728
TI  - Breathing room: the (un)natural history of adipose microhypoxia and insulin
      resistance.

PMID- 19114729
TI  - Sleeping Beauty, awake! Regulation of insulin gene expression by methylation of
      histone H3.

PMID- 19114732
TI  - Outgoing Editor-in-Chief.

PMID- 19114730
TI  - Phosphatidylcholine hydroperoxide-induced THP-1 cell adhesion to intracellular
      adhesion molecule-1.
AB  - The accumulation of phosphatidylcholine hydroperoxide (PCOOH), a primary
      oxidation product of phosphatidylcholine (PC), in blood plasma and tissues has
      been observed in various pathological conditions, including atherosclerosis.
      However, the biological roles of PCOOH in these conditions remain unknown. To
      estimate the atherogenicity of PCOOH, we evaluated the effect of PCOOH on THP-1
      monocytic cell adherence to immobilized vascular endothelial cell adhesion
      molecules. THP-1 cell adhesion to intracellular adhesion molecule-1 (ICAM-1) was
      dose-dependently increased by addition of PCOOH. Phosphatidylcholine hydroxide (a
      hydroxyl analog of PCOOH) also induced THP-1 cell adhesion to ICAM-1, whereas
      nonoxidized PC, sn-2 truncated PCs, and other hydroperoxide compounds did not
      affect the adhesion. In the PCOOH-treated cells, obvious protruding F-actin-rich
      membrane structures were formed, and lymphocyte function-associated antigen-1
      (LFA-1) was localized to the protruding structures. Cytochalasin D, an actin
      polymerization inhibitor, suppressed the PCOOH-induced cell adhesion to ICAM-1
      and the membrane protrusions. These results indicate that PCOOH evokes LFA-1
      mediated cell adhesion to ICAM-1 via actin cytoskeletal organization, and the
      mechanism may participate in monocyte adherence to the arterial wall in the
      initiation of atherosclerosis.

PMID- 19114731
TI  - Characterization of mouse lysophosphatidic acid acyltransferase 3: an enzyme with
      dual functions in the testis.
AB  - Glycerophospholipids are structural and functional components of cellular
      membranes as well as precursors of various lipid mediators. Using acyl-CoAs as
      donors, glycerophospholipids are formed by the de novo pathway (Kennedy pathway)
      and modified in the remodeling pathway (Lands' cycle). Various acyltransferases,
      including two lysophosphatidic acid acyltransferases (LPAATs), have been
      discovered from a 1-acylglycerol-3-phosphate O-acyltransferase (AGPAT) family.
      Proteins of this family contain putative acyltransferase motifs, but their
      biochemical properties and physiological roles are not completely understood.
      Here, we demonstrated that mouse LPAAT3, previously known as mouse AGPAT3,
      possesses strong LPAAT activity and modest lysophosphatidylinositol
      acyltransferase activity with a clear preference for arachidonoyl-CoA as a donor.
      This enzyme is highly expressed in the testis, where CDP-diacylglycerol synthase
      1 preferring 1-stearoyl-2-arachidonoyl-phosphatidic acid as a substrate is also
      highly expressed. Since 1-stearoyl-2-arachidonoyl species are the main components
      of phosphatidylinositol, mouse LPAAT3 may function in both the de novo and
      remodeling pathways and contribute to effective biogenesis of 1-stearoyl-2
      arachidonoyl-phosphatidylinositol in the testis. Additionally, the expression of
      this enzyme in the testis increases significantly in an age-dependent manner, and
      beta-estradiol may be an important regulator of this enzyme's induction. Our
      findings identify this acyltransferase as an alternative important enzyme to
      produce phosphatidylinositol in the testis.

PMID- 19114733
TI  - A framework for the physical development of elite rugby union players.
AB  - Increased professionalism in rugby has resulted in national unions developing
      high-performance models for elite player development, of which physical
      preparation is an important component, to ensure success in future years. This
      article presents a 5-step framework for the physical preparation of elite players
      in a development program. Competition movement patterns and the physical profiles
      of elite players are used as the basis of the framework and reinforce the
      repeated high-intensity nature of Rugby Union. Physical profiling highlights a
      player's strengths and weaknesses in the areas of strength, speed, endurance, and
      body composition. These qualities need to be managed with an understanding of
      their interaction. This framework should be implemented within the yearly plan to
      ensure that benefits are maximized from the training undertaken. The success of
      the framework in developing elite players' progression can be evaluated using
      standardized physical, performance, and competency tests.<

PMID- 19114734
TI  - Monitoring changes in lean mass of elite male and female swimmers.
AB  - PURPOSE: To characterize within-subject changes in anthropometric characteristics
      of elite swimmers within and between seasons. METHODS: The subjects were 77 elite
      swimmers (31 females, 46 males, age 15 to 30 years) monitored over 0.4 to 9.2
      years. One anthropometrist recorded their body mass (M) and sum of 7 skinfold
      thicknesses (S) on 2042 occasions over 14 years from phase to phase within a
      season and over consecutive seasons. We estimated change in lean mass using a
      newly derived index (LMI) that tracked changes in M controlled for changes in S.
      RESULTS: The LMI is M/Sx, where x = 0.16 +/- 0.04 for females and 0.15 +/- 0.05
      for males (mean +/- SD). The LMI of males increased 1.1% (95% confidence limits
      +/- 0.2%) between preseason and taper phases, almost twice as much as that of
      females (0.6% +/- 0.3%). During the same period, M and S fell by approximately 1%
      and approximately 11%, respectively. From season to season LMI increased by 0.9%
      (0.8% to 1.0%) for males and 0.5% (0.3% to 0.7%) for females. All these within
      subject effects on LMI were well defined (+/-approximately 0.3%). The typical
      variation (SD) of an individual's LMI was 1.2% for assessments within a season
      and 1.9% between seasons, with a short-term technical error of measurement of
      approximately 0.5%. CONCLUSION: Coaches and conditioners should typically expect
      a twofold greater increase in lean mass in male swimmers within and between
      seasons than in females. An LMI of the form M/Sx should be useful for monitoring
      individual swimmers and athletes in other sports in which body composition
      affects performance.

PMID- 19114735
TI  - The water-polo intermittent shuttle test: a match-fitness test for water-polo
      players.
AB  - PURPOSE: To develop and validate an intermittent match-fitness test for water
      polo players. METHODS: Eight male junior players performed the Water Polo
      Intermittent Shuttle Test (WIST) twice to assess test reliability. To assess test
      sensitivity and validity, 104 male and female players from different competition
      standards and playing positions were tested. Eighteen players performed the WIST
      5 times throughout a season to track fitness changes. Twelve players performed
      the WIST 48 hours before 4 consecutive National League games, and coaches awarded
      individual match-fitness scores based on game performances to assess the
      relationship between match fitness and test results. Heart rate (HR) and blood
      lactate (La(blood)) were measured during and after each test, respectively.
      RESULTS: Test-retest performance values were 216 +/- 90 vs 229 +/- 96 m (r = .98,
      P = .0001, coefficient of variation [CV] = 5.4%), peak HR 190 +/- 8 vs 192 +/- 10
      bpm (r = .96, P = .0002, CV = 1.2%), and La(blood) 7.0 +/- 1.8 vs 6.4 +/- 1.6
      mmol/L (r = .84, P = .0092, CV = 8.8%). Significant differences were observed
      among different standards of play (range junior regional females 102 +/- 10 m,
      senior international males 401 +/- 30 m) and playing positions (field players 305
      +/- 154 m, center forwards 255 +/- 118, goal keepers 203 +/- 135 m). Test
      performance was lower in the early season (344 +/- 118 m) than the remainder of
      the season (range 459 +/- 138 to 550 +/- 176 m). WIST performance and match
      fitness scores correlated for all field players (r = .57, P = .054) but more
      highly for field players other than center forwards (r = .83, P = .0027).
      CONCLUSIONS: The WIST is a reliable, sensitive, and valid match-fitness test for
      water-polo players. It could become a useful tool to assess the effects of
      different interventions on match fitness.

PMID- 19114736
TI  - Effect of high-intensity resistance training on performance of competitive
      distance runners.
AB  - In a recent study competitive road cyclists experienced substantial gains in
      sprint and endurance performance when sessions of high-intensity interval
      training were added to their usual training in the competitive phase of a season.
      The current study reports the effect of this type of training on performance of
      20 distance runners randomized to an experimental or control group for 5 to 7
      weeks of training. The experimental group replaced part of their usual
      competitive-phase training with 10 x ?30-minute sessions consisting of 3 sets of
      explosive single-leg jumps (20 for each leg) alternating with 3 sets of resisted
      treadmill sprints (5 x ?30-second efforts alternating with 30-second recovery).
      Before and after the training period all runners completed an incremental
      treadmill test for assessment of lactate threshold and maximum running speed, 2
      treadmill runs to exhaustion for prediction of 800- and 1500-m times, and a 5-km
      outdoor time trial. Relative to the control group, the mean changes (+/-90%
      confidence limits) in the experimental group were: maximum running speed, 1.8%
      (+/- 1.1%); lactate-threshold speed, 3.5% (+/-3.4%); predicted 800-m speed, 3.6%
      (+/- 1.8%); predicted 1500-m speed, 3.7% (+/- 3.0%); and 5-km time-trial speed,
      1.2% (+/- 1.1%). We conclude that high-intensity resistance training in the
      competitive phase is likely to produce beneficial gains in performance for most
      distance runners.

PMID- 19114737
TI  - Making meaningful inferences about magnitudes.
AB  - A study of a sample provides only an estimate of the true (population) value of
      an outcome statistic. A report of the study therefore usually includes an
      inference about the true value. Traditionally, a researcher makes an inference by
      declaring the value of the statistic statistically significant or nonsignificant
      on the basis of a P value derived from a null-hypothesis test. This approach is
      confusing and can be misleading, depending on the magnitude of the statistic,
      error of measurement, and sample size. The authors use a more intuitive and
      practical approach based directly on uncertainty in the true value of the
      statistic. First they express the uncertainty as confidence limits, which define
      the likely range of the true value. They then deal with the real-world relevance
      of this uncertainty by taking into account values of the statistic that are
      substantial in some positive and negative sense, such as beneficial or harmful.
      If the likely range overlaps substantially positive and negative values, they
      infer that the outcome is unclear; otherwise, they infer that the true value has
      the magnitude of the observed value: substantially positive, trivial, or
      substantially negative. They refine this crude inference by stating qualitatively
      the likelihood that the true value will have the observed magnitude (eg, very
      likely beneficial). Quantitative or qualitative probabilities that the true value
      has the other 2 magnitudes or more finely graded magnitudes (such as trivial,
      small, moderate, and large) can also be estimated to guide a decision about the
      utility of the outcome.

PMID- 19114738
TI  - Quality assurance in Australian exercise physiology laboratories in quest of
      excellence.

PMID- 19114739
TI  - Power requirements for swimming a world-record 50-m front crawl.

PMID- 19114740
TI  - Persistent fatigue in a female sprint cyclist after a talent-transfer initiative.

PMID- 19114741
TI  - Transfer of strength and power training to sports performance.
AB  - The purposes of this review are to identify the factors that contribute to the
      transference of strength and power training to sports performance and to provide
      resistance-training guidelines. Using sprinting performance as an example,
      exercises involving bilateral contractions of the leg muscles resulting in
      vertical movement, such as squats and jump squats, have minimal transfer to
      performance. However, plyometric training, including unilateral exercises and
      horizontal movement of the whole body, elicits significant increases in sprint
      acceleration performance, thus highlighting the importance of movement pattern
      and contraction velocity specificity. Relatively large gains in power output in
      nonspecific movements (intramuscular coordination) can be accompanied by small
      changes in sprint performance. Research on neural adaptations to resistance
      training indicates that intermuscular coordination is an important component in
      achieving transfer to sports skills. Although the specificity of resistance
      training is important, general strength training is potentially useful for the
      purposes of increasing body mass, decreasing the risk of soft-tissue injuries,
      and developing core stability. Hypertrophy and general power exercises can
      enhance sports performance, but optimal transfer from training also requires a
      specific exercise program.

PMID- 19114742
TI  - Positional performance profiling of elite ice hockey players.
AB  - PURPOSE: The primary purpose of this study was to determine whether positional
      profiling is possible for elite ice hockey players by examining anthropometric
      characteristics and physiological performance. In addition, performance ranges
      and percentiles were determined for each position (forwards, defensemen, and
      goalkeepers) on all dependent variables. METHODS: A retrospective, cross
      sectional study design was used with performance data from ice hockey players
      (mean age = 18.0 +/- 0.6 years) attending the 2001 (n = 74), 2002 (n = 84), and
      2003 (n = 92) Combines. Four anthropometric characteristics and 12 performance
      tests were the dependent variables. A 3 x 3 (position x year) 2-way ANOVA was
      used to determine whether any significant interactions were present. No
      significant interactions were observed, so the data were collapsed over the 3
      year period and positional characteristics were analyzed using a 1-way ANOVA.
      RESULTS: Defenders were heavier and/or taller compared with the other 2 positions
      (P <or= .01), whereas goalkeepers showed greater body-fat percentage compared
      with that of forwards (P = .001). It was found that goalkeepers had significantly
      lower strength measures for the upper body (P <or= .043) and lower anaerobic
      capacity (P <or= .039) values compared with at least one other position, but they
      had greater flexibility (P <or= .013). No positional differences were observed
      for the broad jump, vertical jump, aerobic power, or curl-ups. CONCLUSION: The
      current findings provide evidence supporting the use of anthropometric
      measurements, upper body strength, and anaerobic capacity to effectively
      distinguish among positions for elite-level ice hockey players.

PMID- 19114743
TI  - The development of a standardized skill assessment for junior volleyball players.
AB  - PURPOSE: To develop a skill assessment for junior volleyball players and to
      evaluate the reliability, validity, and sensitivity of the test for detecting
      training-induced improvements in skill. METHODS: Thirty junior volleyball players
      (mean +/- SD age, 15.5 +/- 1.0 years) participated in this study. Subjects
      performed tests of spiking, setting, serving, and passing skills on 2 separate
      occasions to determine test-retest reliability of accuracy. Two expert coaches
      evaluated the players' technique and reevaluated it 1 month after the initial
      evaluation to determine the intratester reliability for technique measurements. A
      third expert coach determined the intertester reliability for technique
      measurements. The validity of the test to discriminate players of different
      playing abilities was evaluated by testing junior national, state, and novice
      volleyball players. Finally, each player participated in an 8-week skill-based
      training program. RESULTS: Accuracy measurements and intratester and intertester
      ratings of players' technique proved to be highly reproducible (intraclass
      correlation coefficient, r, .85 to .98, range of typical error of measurement
      0.2% to 10.0%). A progressive improvement in skill was observed with increases in
      playing level, while training-induced improvements were present in all skill
      tasks. CONCLUSIONS: These results demonstrate that skill-based testing offers a
      reliable method of quantifying development and progress in junior volleyball
      players. In addition, the skill-testing battery was useful in successfully
      discriminating playing ability among junior volleyball players of varying levels,
      and it was sensitive to changes in skill with training. These findings
      demonstrate that skill-based testing is useful for monitoring the development of
      junior volleyball players.

PMID- 19114744
TI  - The effect of training volume on the acute response and adaptations to resistance
      training.
AB  - PURPOSE: To examine the acute response to 2 resistance-exercise protocols
      performed to repetition failure, but different in load configuration, and
      determine whether the acute response was related to strength increases after 8
      weeks of training. METHODS: Eighteen resistance-trained men completed a single
      session of 2 resistance-exercise protocols. The constant-load protocol (CL)
      required subjects to complete 3 sets of single-arm preacher curls (elbow flexion)
      to failure using a load of approximately 77% 1RM. The reduced-load protocol (RL)
      was similar, but training load was reduced for the second and third sets. Maximal
      isometric force (MVIC) and blood lactate were assessed preprotocol and
      postprotocol to determine the acute response. For the 8-week training phase,
      subjects (N = 12) were divided into 2 programs, each corresponding to 1 of the
      protocols. Strength was measured before and after training. RESULTS: MVIC
      decreased from 106.2 +/- 13.8 to 84.3 +/- 12.1 N . m and from 109.1 +/- 14.7 to
      82.5 +/- 13 N . m after the CL and RL protocols, respectively. The decrements in
      MVIC were significant (P < .001), with the decline after RL tending to be greater
      (P = .051). Postprotocol blood lactate concentrations after CL and RL were 3.4 +/
      1.1 and 4.1 +/- 1.3 mmol/L, respectively, with greater increases after RL (P =
      .036). Similar and significant 1RM strength increases were observed after both
      programs (from 20.7 +/- 2.7 to 23.3 +/- 3.5 kg after CL and from 22.4 +/- 2.9 to
      25.5 +/- 3.2 kg after RL; P < .001). CONCLUSION: The similar increases in
      strength suggest that either the greater acute response to RL was not related to
      the increases in strength or a minimal (threshold) response was achieved during
      both programs.

PMID- 19114745
TI  - A prediction model for peak power output from different incremental exercise
      tests.
AB  - CONTEXT: There is currently no model that predicts peak power output (PPO)
      thereby allowing comparison between different incremental exercise test (EXT)
      protocols. In this study we have used the critical power profile to develop a
      mathematical model for predicting PPO from the results of different EXTs.
      PURPOSE: The purpose of this study was to examine the level of agreement between
      actual PPO values and those predicted from the new model. METHODS: Eleven male
      athletes (age 25 +/- 5 years, VO(2max) 62 +/- 8 mL . kg(-1) . min(-1)) completed
      3 laboratory tests on a cycle ergometer. Each test comprised an EXT consisting of
      1-min workload increments of 30 W (EXT30/1) and 3-min (EXT25/3) and 5-min
      workload increments (EXT25/5) of 25 W. The PPO determined from each test was used
      to predict the PPO from the remaining 2 EXTs. RESULTS: The differences between
      actual and predicted PPO values were statistically insignificant (P > .05). The
      random error components of the limits of agreement of <or=30 W also indicated
      acceptable levels of agreement between actual and predicted PPO values.
      CONCLUSIONS: Further data collection is necessary to confirm whether the model is
      able to predict PPO over a wide range of EXT protocols in athletes of different
      aerobic and anaerobic capacities.

PMID- 19114746
TI  - The yo-yo test: reliability and association with a 20-m shuttle run and VO(2max).
AB  - PURPOSE: The purpose of the study was to determine the reliability of yo-yo
      intermittent recovery test (yo-yo) scores and their degree of association with a
      20-m shuttle run (20MSR) and VO(2max) values. METHODS: Subjects were elite
      (Australian Football League [AFL], n = 23), state-level (hockey, n = 15, and
      cricket, n = 27), and recreational team-sport players (n = 33). All performed a
      20MSR and the yo-yo at either level 1 (recreational and state level) or level 2
      (AFL). A recreational subgroup (n = 19) also performed a treadmill VO(2max) test.
      RESULTS: Test-retest results found the yo-yo (levels 1 and 2) to be reliable (ICC
      = .86 to .95). The 20MSR and yo-yo level 1 scores correlated (P < .01) in the
      recreational (r = .81 to .83) and state-level groups (r = .84 to .86), and 20MSR
      and yo-yo level 2 scores, in the elite (r = .86) and recreational groups (r = .55
      to .57). The VO(2max) and yo-yo level 1 scores in the recreational group
      correlated (P < .01, r = .87), but no association was found with yo-yo level 2 (r
      = .40 to .43, nonsignificant). CONCLUSIONS: We conclude that level 1
      (recreational and state level) and level 2 (elite) yo-yo scores were both
      strongly associated with 20MSR scores and VO(2max) (level 1: recreational
      subjects only). The yo-yo appears to measure aerobic fitness similarly to the
      20MSR but may also be used as a field test of the ability to repeat high
      intensity efforts.

PMID- 19114747
TI  - Physical fitness components associated with performance in a multiple-sprint
      test.
AB  - PURPOSE: The 5-m repeat-sprint test (5-m RST) measures resistance to fatigue
      after repeated bouts of short-duration, high-intensity activity. This study
      determined the components of fitness associated with performance in 5-m RSTs.
      METHODS: Speed (10-m and 40-m sprints), strength (bench press), agility, strength
      endurance (pull-ups and push-ups), and aerobic power (20-m shuttle-run test) were
      measured in male provincial- or national-level rugby (n = 110), hockey (n = 59),
      and soccer (n = 55) players. RESULTS: Subjects with either high (HI) or low (LO)
      resistance to fatigue in the 5-m RST differed in body mass (76.9 +/- 11.6 kg vs
      102.1 +/- 18.9 kg, HI vs LO, respectively, P < .001), agility (14.55 +/- 0.41
      seconds vs 15.56 +/- 0.30 seconds, P < .001), bench press (86 +/- 20 kg vs 114 +/
      33 kg, P = .03), pull-ups (13 +/- 4 vs 8 +/- 5, P = .02), push-ups (56 +/- 12 vs
      39 +/- 13, P = .002), and 20-m shuttle-run test (20-m SRT; 133 +/- 11 vs 87 +/-
      12 shuttles, P < .001). Body mass, strength, and aerobic power were the best
      predictors of 5-m RST performance: 5-m RST = -1.274(mass) + 0.756(1RM bench
      press) + 2.053(number of 20-m SRT shuttles) + 549.409 (R2 = .66). CONCLUSIONS:
      Performance in the 5-m RST is predicted best by a combination of factors
      including body mass, strength, and aerobic ability, rather than by any single
      component of fitness.

PMID- 19114748
TI  - Sports-science roundtable: does sports-science research influence practice?
AB  - As sports scientists, we claim to make a significant contribution to the body of
      knowledge that influences athletic practice and performance. Is this the reality?
      At the inaugural congress of the Australian Association for Exercise and Sports
      Science, a panel of well-credentialed academic experts with experience in the
      applied environment debated the question, Does sports-science research influence
      practice? The first task was to define "sports-science research," and it was
      generally agreed that it is concerned with providing evidence that improves
      sports performance. When practices are equally effective, sports scientists also
      have a role in identifying practices that are safer, more time efficient, and
      more enjoyable. There were varying views on the need for sports-science research
      to be immediately relevant to coaches or athletes. Most agreed on the importance
      of communicating the results of sports-science research, not only to the academic
      community but also to coaches and athletes, and the need to encourage both short-
      and long-term research. The panelists then listed examples of sports-science
      research that they believe have influenced practice, as well as strategies to
      ensure that sports-science research better influences practice.

PMID- 19114749
TI  - Technical issues in quantifying low-frequency fatigue in athletes.
AB  - A recent review by Cairns and colleagues published in Exercise and Sport Sciences
      Reviews (2005:33[1]:9-16)1 described experimental models used to study
      neuromuscular fatigue and explained the inherent strengths and weaknesses of
      applied versus reductionist approaches. This technical report addresses some of
      the recommendations made in that review, from the perspective of the applied
      sport scientist or practitioner in evaluating fatigue in elite athletes. The goal
      here is to highlight the inherent difficulties in assessing fatigue in the
      applied sport setting and to provide practitioners with future directions for
      fatigue research. A particular type of fatigue, called low-frequency fatigue
      (LFF), is of particular interest to the applied sport scientist or practitioner
      and could be the focus of future work. This report identifies some of the
      technical challenges faced in developing a practical test of LFF for use in the
      field setting. The outcome of further work in this area will lead to a better
      understanding of athlete monitoring, training, and performance.

PMID- 19114750
TI  - Assessment of an international breaststroke swimmer using the 7 x 200-m step
      test.
AB  - Thompson and Cooper1 observed that improvements in the swimming speed at 2-mM and
      6-mM lactate concentration coincided with improvements in competitive
      breaststroke performances, whereas Pyne et al concluded that changes in swimming
      speed at lactate threshold were not directly associated with competition
      performances in a mixed-stroke group of 12 elite swimmers. This case study
      presents data from eleven (7 x 200 m) step tests over a 3-year period for a world
      class 200-m male breaststroke swimmer. Personal-best race times were reduced by
      9.5 seconds over this period. For this individual, step-test data provided
      valuable information with regard to the swimmer's readiness for performance,
      health and training status, and nutritional habits.

PMID- 19114751
TI  - Nausea and high serum osmolality during a simulated ultraendurance adventure
      race: a case-control study.
AB  - PURPOSE: A 29-year-old elite adventure-race athlete presented with a 10-month
      history of nausea appearing during or after ultraendurance races. The athlete
      noted recent worsening of symptoms, including lightheadedness, dark rings under
      the eyes, and weakness as nausea became worse, and was unable to complete races.
      Possible diagnoses included dehydration or overhydration, renal damage, and
      gastrointestinal malfunction. METHODS: The subject (S) and a case-control athlete
      (C) performed an 11-hour simulated race (field test) ending in the laboratory.
      Blood samples were drawn, and body mass and food and drink ingested were noted at
      regular intervals. RESULTS: Symptoms were replicated in S, whose vomitus
      contained undigested solids consumed during exercise. Over 11 hours, fluid loss
      was similar in S (9.6 L) and C (10.3 L), but fluid intake for S was 4.8 L versus
      9.9 L for C. Body mass decreased 6% in S and 1.8% in C. S presented with elevated
      serum urea and creatinine before and after and elevated osmolality after the
      field test. A week after the field test, creatinine clearance was low in S but
      not C (83 vs 160 mmol per 24-hour urine, respectively). S was instructed to
      increase fluid intake throughout the day, to match fluid lost during training,
      and to refrain from long races. After 2 months, his serum urea, creatinine, and
      osmolality were normal, and creatinine clearance improved to 133 mmol per 24-hour
      urine. He repeated the field test and experienced no nausea. CONCLUSIONS: Nausea
      in ultraendurance athletes might be an early symptom of chronic but reversible
      renal strain or insensitivity to high osmolality.

PMID- 19114752
TI  - [A structural equation model on sexual function in women with gynecologic
      cancer].
AB  - PURPOSE: This study was designed to construct and test a structural equation
      model on sexual function in women with gynecologic cancer. METHODS: The model was
      constructed and tested under the hypotheses that women's physical changes in
      sexual function after gynecologic cancer treatment did not automatically lead to
      sexual dysfunctions. Women's psychosocial factors were considered to be mediating
      variables. Two hundred twelve women with cervical, ovarian, and endometrial
      cancer were recruited and asked to complete a survey on their physical factors,
      psychosocial factors and sexual function. Data was analyzed using SPSS WIN 12.0
      and Amos WIN 5.0. RESULTS: Predictors of sexual function in the final model were
      sexual attitude affected by physical distress and couple's age, sexual
      information affected by physical distress and couple's age, depression affected
      by physical distress, and marital intimacy affected by physical distress. Tumor
      stage and time since last treatment directly affected women's sexual function
      without any mediating psychosocial variables. However, body image did not affect
      women's sexual function. CONCLUSION: Nursing professionals should develop a
      tailored educational program integrating both physical and psychosocial aspects,
      and apply it to women and their spouses in order to promote sexual function in
      women with gynecologic cancer.

PMID- 19114753
TI  - [Factors influencing quality of life in patients with gastrointestinal
      neoplasms].
AB  - PURPOSE: The purpose of this study was to identify the factors influencing
      quality of life after analyzing the relationship between depression, health
      promotion and quality of life in patients with gastrointestinal neoplasms.
      METHODS: The subjects of this study were 63 people who underwent treatments from
      2 general hospitals in Seoul and Daejeon and had no recurrence in stages I & II
      of gastrointestinal neoplasms. Data was collected from March 1 to April 30, 2006.
      A questionnaire consisting of Center for Epidemiologic Studies Depression (CES
      D), Health Promoting Lifestyle Profile II (HPLP II) and Functional Assessment of
      Cancer Therapy-Colorectal (FACT-C) was given. The collected data was analyzed
      with the SPSS program which was used for descriptive statistics, Pearson
      correlation coefficients and hierarchical multiple regression. RESULTS: The major
      findings of this study were as follows: 1) There was a significant relationship
      between depression (r=-.639, p=.000), health promotion (r=.407, p=.001) and
      quality of life. 2) Significant factors were depression (F=-4.091, p=.000) and
      health promotion (F=2.375, p=.021) that explained 46% of quality of life
      (F=10.022, p=.000). CONCLUSION: Cancer patients experienced extreme depression
      which led to a negative effect on quality of life. Health promotion was an
      important variable to the quality of life and it gave the patients motivation for
      having a will and belief for better health.

PMID- 19114754
TI  - [Development of nursing key performance indicators for an intensive care unit by
      using a balanced scorecard].
AB  - PURPOSE: The purpose of this study was to develop visions of nursing service,
      nursing strategies and key performance indicators (KPIs) for an intensive care
      unit (ICU) based on a Balanced Scorecard (BSC). METHODS: This study was
      undertaken by using methodological research. The development process consisted of
      four phases; the first phase was to develop the vision of nursing in ICUs. The
      second phase was to develop strategies according to 4 perspectives of a BSC. The
      third phase was to develop KPIs according to the 4 perspectives of BSC and the
      final phase was to combine the nursing visions, strategies and KPIs of ICUs.
      RESULTS: Two main visions of nursing service for ICUs were established. These
      were 'realization of harmonized professional nursing with human respect' and
      'recovery of health through specialized nursing' respectively. In order to reach
      the aim of developing nursing visions, thirteen practical strategies and nineteen
      KPIs were developed by four perspectives of the BSC. CONCLUSION: The results will
      be used as objective fundamental data to attain business outcomes for the
      achievement of nursing visions and strategies of ICUs.

PMID- 19114755
TI  - [The relationship between lifetime sports activity measured with MET and peak
      strain score and bone measurement in college-aged women].
AB  - PURPOSE: The aim of this study was to compare the relation between differently
      measured sports activities (metabolic equivalent [MET] and peak strain score) and
      distal radius bone mineral density in college-aged women. METHODS: Lifetime
      sports activity was scored in two different ways: 1) a sports activity score by
      multiplying the intensity (METs) and duration and 2) a sports activity score by
      adding up physical strain scores based on the ground reaction force of each
      sports activities. Bone mineral density was measured using dual energy x-ray
      densitometry (DTX-200) in the distal radius site. RESULTS: In stepwise multiple
      regression analysis, body weight and sports activities during the college period
      were significant positive predictors for distal radius bone mineral density. The
      explained variance of sports activity measured with a peak strain score (8.8%)
      for distal radius bone mineral density was higher than one measured with the MET
      score (3.3%). CONCLUSION: It can be concluded that sports activity scores based
      on MET and peak strain scores during college are very important for determining
      the bone mineral density in the distal radius site in women under 30.

PMID- 19114756
TI  - [Falls risk factors of inpatients].
AB  - PURPOSE: The purpose of this study was to identify the risk factors for falls and
      to suggest data for developing a program for preventing falls. METHODS: This was
      a case-control study in five university hospitals and a general hospital. In
      total, 216 patients over the age of 18 yr admitted from January 1 to December 31,
      2007 participated. One hundred eight patients with experience of falling were
      matched by gender, age level, diagnosis, and length of stay with 108 patents with
      no experience of falling admitted on the same unit. A quality assurance
      coordinator nurse in each hospital examined 35 fall risk factors developed by
      researchers. RESULTS: In acute hospitals, history of falls, orientation ability,
      dizziness or vertigo, general weakness, urination problems, transfer/mobility
      difficulty, walking dependency, impatience, benzodiazepines, diuretics, and
      vasodilators showed significance on adjusted-odds ratios for fall. Logistic
      regression analysis was performed to elucidate the factors that influence falls.
      The probability of falls was increased by dizziness/vertigo, general weakness,
      and impatience/agitation. CONCLUSION: This finding can be used as a useful
      resource in developing nursing intervention programs to predict and prevent the
      falls of inpatients.

PMID- 19114757
TI  - [Comparative study on the sleep patterns, satisfaction of sleep, and sleep
      enhancement behaviors between hospitalized and non-hospitalized elderly].
AB  - PURPOSE: This study was to compare and analyze sleep patterns, satisfaction of
      sleep, and sleep enhancement behaviors between hospitalized and non-hospitalized
      elderly. METHODS: Subjects were 201 older adults, who were hospitalized patients
      or living in U-city, Gyung-gi province. Data was collected from June 10 to August
      25, 2007, and was analyzed by the SAS program. RESULTS: 1) Non-hospitalized
      elderly had better sleep patterns than hospitalized elderly patients. 2) There
      was a strong positive correlation between sleep patterns and satisfaction of
      sleep in both groups. 3) In hospitalized elderly, there were significant
      differences in sleep patterns and satisfaction of sleep by month. 4) In non
      hospitalized elderly, there was a significant difference in sleep patterns by
      presence or absence of spouses. There was a significant difference in
      satisfaction of sleep by those living with others. There were significant
      differences in sleep enhancement behaviors by age, religion, length of time, and
      sponsors. CONCLUSION: To relieve sleep disturbances of elderly, comprehension of
      sleep of the aged by nursing care givers should be obtained. Also, improving
      environments and elder's self-esteem with religious consideration and preparation
      of financial conditions are needed to promote the sleep of hospitalized and non
      hospitalized elderly.

PMID- 19114758
TI  - [Quality of life in low income Korean aged].
AB  - PURPOSE: The purpose of this study was to identify the quality of life and its
      predictors in low income Korean aged. METHODS: This was a predictive
      correlational study. An accessible sample from the population of people who were
      65 and over and were supported by the basic livelihood security system was 1,040.
      Quota sampling with strata of state division in the nation was chosen. Quality of
      life and its predictors in the subjects were measured. RESULTS: The mean quality
      of life in the subjects was 47.0+/-10.7. Predictors of this study significantly
      explained 54.3% of the total variance of quality of life. Depression was the most
      significant predictor of quality of life. Health problems, district, social
      support, leisure activity, and health behavior had effects on quality of life.
      CONCLUSION: This finding indicates that quality of life in lower income Korean
      aged is different from other populations by economic status. Demographics, health
      status and social status were predictors of quality of life in the aged with a
      small income.

PMID- 19114759
TI  - [The effects of psychosocial rehabilitation programs on the levels of self
      efficacy for mentally disabled persons].
AB  - PURPOSE: This study investigated the effects of psychosocial rehabilitation
      programs provided by a psychosocial rehabilitation center on the levels of self
      efficacy for mentally disabled persons. We followed the study subjects for 2 yr
      in order to examine whether the psychosocial rehabilitation programs had a
      positive impact on their levels of self-efficacy. METHODS: There were 18 subjects
      in the experimental group and they received all the psychosocial rehabilitation
      services available at the psychosocial rehabilitation center for 2 yr. In the
      comparison group, there were 17 participants who voluntarily refused to
      participate in the psychosocial rehabilitation programs. RESULTS: The results
      indicated that the psychosocial rehabilitation programs were effective in
      increasing the levels of the self-efficacy total score and specific self-efficacy
      score. CONCLUSION: The overall study results indicated that psychosocial
      rehabilitation programs provided by a psychosocial rehabilitation center had a
      positive impact on increasing the levels of self-efficacy for mentally disabled
      persons.

PMID- 19114760
TI  - [Factors associated with social isolation in older adults using senior welfare
      centers].
AB  - PURPOSE: The purpose of this study was to investigate the factors associated with
      social isolation in older adults using a senior welfare center. METHODS: This
      study was a cross-sectional survey. Data was collected from June to August 2006
      using a questionnaire. A total of 248 older adults responded. RESULTS: About one
      third (34.9%) of participants responded they felt socially isolated. There were
      statistically significant differences in living, religion, family and
      belongingness social support, loneliness, depression, family function, perceived
      health status, and number of chronic illnesses between socially isolated and non
      isolated groups. However, factors influencing social isolation were family
      function (OR=0.954, CI=0.926-0.982), loneliness (OR=1.042, CI=1.002-1.083),
      depression (OR=1.041, CI=1.002-1.081), and number of chronic illness (OR=1.657,
      CI=1.153-2.382). CONCLUSION: We found that some older adults were feeling
      socially isolated even though the senior welfare center was a good place to meet
      people. The findings of this study indicated that older adults suffering from
      social isolation need special attention and may benefit from interventions which
      promote health and social interactions. Further studies are needed to develop and
      evaluate an intervention program for this population.

PMID- 19114761
TI  - [The effects of preemptive analgesia of morphine and ketorolac on postoperative
      pain, cortisol, O(2) saturation and heart rate].
AB  - PURPOSE: This study investigated the preemptive analgesic effects of Morphine and
      Ketorolac on postoperative pain, cortisol, O(2)saturation and heart rate for the
      first 24 hr after abdominal surgery. METHODS: Data collection was performed from
      April 1 to September 30, 2006. Forty patients undergoing a gastrectomy under
      general anesthesia were randomly allocated to the experimental or control group.
      The experimental group (20 patients) was administered Morphine and Ketorolac
      approximately 1 hr prior to skin incision, but the control group (20 patients)
      was administered Morphine and Ketorolac at peritoneum closure through a patient
      controlled analgesia (PCA) pump. Postoperative pain, blood pressure, heart rate,
      cortisol, O(2)saturation, frequency of the PCA button pressed and doses of
      additional analgesics were observed through post operative 24 hr. Collected data
      was analyzed using t-test, chi(2)test, repeated measures ANOVA, and Bonferroni
      methods. RESULTS: Postoperative pain, cortisol, the frequency of PCA button
      pressed, and dose of additional analgesics of the experimental group were
      significantly lower than the control group. There were no statistical differences
      in blood pressure, heart rate and O(2)saturation between the experimental group
      and control group. CONCLUSIONS: We concluded that administration of morphine and
      ketorolac at 1 hr prior to skin incision resulted in decreasing postoperative
      pain, but it didn't affect blood pressure, heart rate or O(2)saturation for 24 hr
      after abdominal surgery.

PMID- 19114762
TI  - [The mediating effect of depression in the relationship between muscle strength
      of extremities and falls among community-dwelling elderly].
AB  - PURPOSE: The purpose of this study was to identify the mediating effect of
      depression in the relationship between muscle strength of extremities and falls
      among community-dwelling elderly. METHODS: Two hundred forty-seven participants
      were recruited from a public health center, a hall for the aged and a school for
      the aged in B city. Face-to-face interviews were conducted using questionnaires
      from May to September of 2007. Data was analyzed with descriptive statistics,
      Pearson correlation, and multiple regression using the SPSS WIN 14.0 program.
      RESULTS: There was a significantly negative relationship between muscle strength
      of lower extremities and falls, muscle strength of left upper extremity and
      falls, and muscle strength of right upper extremity and falls. Depression
      positively correlated with falls. Depression showed mediating effects between
      muscle strength of extremities and falls. Weakness of muscle strength of
      extremities increased depression and the increased depression increased the
      frequencies of falls. CONCLUSION: For the effective management and prevention of
      community-dwelling older adults' falls, exercise programs including depression
      decreasing strategies should be established. These exercise programs can decrease
      depression which is the mediator role between the degrees of muscle strength of
      extremities and falls.

PMID- 19114763
TI  - [The life of elderly women living alone].
AB  - PURPOSE: This study aimed to uncover the fundamental nature of living alone in
      female elderly. METHODS: The phenomenological research approach developed by van
      Manen was adopted. RESULTS: The theme was 'taking a firm stand alone on the edges
      of life'. The composition elements of living alone experienced by elderly women
      were as follows: 1) Corporeality: participants perceived their bodies by their
      health status. Unhealthy participants were suffering with diseases and dependant
      on other persons, while healthy participants were free from family responsibility
      and kept on moving. 2) Spatiality: participants felt both freedom and loneliness
      while they stayed home. 3) Relationality: participants felt pity and yearning for
      their bereaved husband and sometimes talked to his picture. According to their
      children's filial piety, participants were pleased or displeased. However, they
      incessantly devoted themselves to their children. 4) Temporality: participants
      considered the rest of their life as extra-time which was proceeding to death,
      and tried to keep themselves busy before they died. CONCLUSION: A nurse should
      understand the multifarious aspects of elderly women's life, and then intervene
      to consolidate their strengths for self-supporting the final years of life.

PMID- 19114764
TI  - [Menstrual attitudes and maternal child rearing attitudes in middle school female
      students].
AB  - PURPOSE: This correlational study was performed to identify the impacts of
      maternal child rearing attitudes on the menstrual attitudes and the determinants
      of positive menstrual attitudes in female middle school students. METHODS: With
      convenience sampling, 198 middle school female students were recruited living in
      one major city and its surrounding areas in Korea. Data was collected using a
      self administered questionnaire including menstrual attitudes and maternal child
      rearing attitudes from April 1 to July 15, 2008. RESULTS: Among the Maternal
      child rearing attitudes, affectionate, achievement oriented and rational
      attitudes had positive correlations to a positive menstrual attitude, and an
      autonomous attitude had a negative correlation to a negative menstrual attitude.
      As determinants of positive menstrual attitudes, feeling of menarche, mother's
      response at first menstruation, and rational maternal child rearing attitudes
      were delineated and their explained variance for a positive menstrual attitude
      was 18.5%. There was no difference on menstrual attitudes by K clustering in
      terms of maternal child rearing attitudes. CONCLUSION: These results support the
      critical role of the mother. Especially desirable maternal child rearing
      attitudes in relation to a positive menstrual attitude would be affectionate,
      achievement oriented and rational for early adolescent girls. In further studies,
      considerations are needed for menstruation related education and research for
      early adolescents and active involvement of the mother & daughter together.

PMID- 19114765
TI  - [Meaning of life in wives of alcoholics: autobiographical method].
AB  - PURPOSE: The purpose of this study was to explore and describe life-stories and
      meanings of life in wives of alcoholics by analyzing their autobiographies.
      METHODS: Autobiographies were collected from 20 participants who produced their
      own autobiographies in the logotherapeutic autobiography program at community
      alcohol counseling centers in Korea. The data were coded to identify themes of
      agency and communion using the manual coding system developed by McAdams, and
      analyzed by the existential approach. RESULTS: There were 214 coded episodes in
      twenty autobiographies. There were 128 agency themes and 86 communion themes. The
      most common themes were Love/Friendship. Five themes emerged from the
      autobiographical episodes on the existential perspective: 1) overcoming the
      suffering, 2) meaningful people and relationships, 3) spiritual maturation, 4)
      caring and helping, and 5) finding a meaning of life. CONCLUSION: These results
      showed that the wives of alcoholics who participated in the logotherapeutic
      autobiography program found the meaning of life through their suffering.
      Furthermore, a study on existential nursing interventions for people who have
      meaninglessness in life needs to be done.

PMID- 19114766
TI  - [Re-employment experience of nurses who have left the profession].
AB  - PURPOSE: The purpose of this study was to explore the re-employment process of
      inactivated nurses returning to the nursing field and to develop a grounded
      theory about their re-employment experiences. METHODS: Data was collected through
      a face-to-face interview and telephone interviews from 10 nurses. The ground
      theory methodology of Strauss and Corbin (1998) was used for theoretical sampling
      in accordance with their unemployment period and reason for leaving prior to re
      employment; whereas works of data collection and analysis were performed
      concurrently. RESULTS: The core category was discovered to be 'identifying a
      career path by striking a balance between the practical and the ideal'. This
      series of processes was categorized into five stages: 'trying to get a job
      again', 'tolerating difficulties as a beginner', 'trying their best to remain a
      nurse', 'trying to get another job', and 'staying in the profession till the
      end'. CONCLUSION: The results of this study suggest an understanding and profound
      insight on the issue of a nursing shortage.

PMID- 19114768
TI  - Enteric infections and diagnostic testing.
AB  - PURPOSE OF REVIEW: Gastrointestinal pathogens profoundly affect human health and
      well being. The provider's ability to render optimal care often highly depends on
      diagnostic microbiologic support. We aim to provide a clinically pertinent
      assessment of the current state of our ability to diagnose human gastrointestinal
      pathogens and describe (and decry) the unsophistication of many current
      diagnostic methods and strategies. RECENT FINDINGS: Recent advances involve
      improved stool polymerase chain reaction assays and application of this
      technology to a broader panel of pathogens, stool antigen assays, and improved
      culture techniques, but there is little penetration of such diagnostic advances
      into clinical practice. Many such techniques remain limited to research or
      epidemiologic use and are not typically available in the clinical laboratory.
      SUMMARY: Multiple clinical and laboratory factors need to be considered when
      attempting to diagnose the wide variety of gastrointestinal pathogens afflicting
      humans. Careful interpretation of diagnostic tests with attention to the
      population studied and the characteristics of each test is necessary.

PMID- 19114769
TI  - Enteroaggregative Escherichia coli infection.
AB  - PURPOSE OF REVIEW: To review studies that improve the current knowledge on the
      epidemiology, virulence factors, detection, and chronic complications of
      enteroaggregative Escherichia coli (EAEC) infection. RECENT FINDINGS: EAEC
      infection is an important cause of diarrhea in outbreak and non-outbreak settings
      in developing and developed countries. In the USA, EAEC is one of the most common
      bacterial pathogens identified in cases of diarrhea not associated with
      immunodeficiency or foreign travel. Important advances have been made in the
      understanding of the pathogenesis of this enteropathogen. The extracellular
      matrix proteins fibronectin, laminin, and collagen IV have been shown to function
      as receptors for adherence frimbriae. A distinct aggregative adherence pilin hdaA
      has been identrified. The diagnosis of EAEC depends on the observation of the
      characteristic 'stacked-brick' like adhesion pattern when co-cultured with HEp-2
      cells. At the molecular level, strains demonstrating the aggregative phenotype
      are heterogeneous; however, several virulence factors can be detected by
      polymerase chain reaction. Several EAEC proteins have shown antigenicity and
      could become vaccine candidates. Recently, infection with EAEC has been
      implicated in the development of irritable bowel syndrome, but this remains to be
      confirmed. SUMMARY: There has been significant progress in understanding the
      pathogenesis and clinical profile of EAEC infection.

PMID- 19114770
TI  - Probiotics as prevention and treatment for diarrhea.
AB  - PURPOSE OF REVIEW: To critically appraise evidence on probiotic use for
      prevention and treatment of diarrhea in children and adults. RECENT FINDINGS:
      Several randomized controlled trials and meta-analyses suggested that probiotics
      are effective in primary and secondary prevention of gastroenteritis and its
      treatment. Selected Lactobacillus strains had a modest, although significant
      effect in primary prevention. Saccharomyces boulardii was effective in antibiotic
      associated and in Clostridium difficile diarrhea. There is evidence that it might
      prevent diarrhea in day-care centers. Lactobacillus rhamnosus GG was associated
      with reduced diarrheal duration and severity, more evident in case of childhood
      Rotavirus diarrhea. Similar, although weaker, evidence was obtained with S.
      boulardii. Both strains are included in evidence-based recommendations for
      gastroenteritis management in children. Data on other Lactobacillus strains are
      preliminary. Probiotic efficacy was related to cause, early administration and
      bacterial load, and their mechanisms were associated with antiinfectious action
      in the intestine or, indirectly, to modulation of innate and adaptive immunity.
      SUMMARY: Probiotics have gained a role as adjunctive treatment of infantile
      gastroenteritis together with rehydration. Their efficacy is less convincing in
      adults, but promising in antibiotic-associated diarrhea. However, evidence of
      efficacy is limited to a few strains.

PMID- 19114771
TI  - Renewed interest in a difficult disease: Clostridium difficile infections-
      epidemiology and current treatment strategies.
AB  - PURPOSE OF REVIEW: Renewed interest in Clostridium difficile infections (CDI) is
      stimulating research into the pathogenesis and virulence factors for this
      pathogen. This review summarizes recent progress in the field, particularly in
      relation to the changing epidemiologic trends and new investigational treatments.
      RECENT FINDINGS: Elucidation of the role of different toxins of C. difficile
      (tcdA, tcdB and binary toxin) is deepening our understanding of CDI. Stain typing
      of C. difficile isolates is documenting the spread of an emergent strain
      (BI/NAP1/027) associated with large outbreaks of severe disease. Typing of
      isolates around the world shows global spread of this strain. Reliance upon
      metronidazole is questioned due to a lower response rate and newer
      investigational therapies are reported. SUMMARY: After being considered a
      manageable pathogen for decades, C. difficile recently caused large outbreaks of
      severe disease. Refocused research is determining patients who are at risk for
      CDI, what methods are more effective in diagnosing CDI and what new treatments
      may be effective. This article reviews the recent findings in the literature
      regarding this difficult and challenging pathogen.

PMID- 19114772
TI  - Rotavirus vaccines and pathogenesis: 2008.
AB  - PURPOSE OF REVIEW: Rotaviruses cause life-threatening gastroenteritis in children
      throughout the world. The burden of disease has resulted in the development of
      two live, attenuated vaccines that are now licensed in many countries. This
      review summarizes new data on these vaccines, their effectiveness, and remaining
      challenges including new data on the rotavirus enterotoxin, a potential antiviral
      target. RECENT FINDINGS: Live attenuated rotavirus vaccines are used to protect
      infants against severe rotavirus-induced gastroenteritis and, RotaTeq, a
      pentavalent bovine-based vaccine, and, Rotarix, a monovalent human rotavirus, are
      now currently licensed in many countries. Initial results of the licensed RotaTeq
      vaccine have been promising in the USA and results of immunogenicity and efficacy
      in developing countries are expected soon. However, universal vaccine
      implementation is challenging due to age limitations on administration of these
      vaccines. Chronic rotavirus infections in immunocompromised children may remain a
      problem and require the development of new treatments including antiviral drugs.
      Increasing data on the mechanisms of action of the rotavirus enterotoxin
      highlight this pleiotropic protein as a good target as well as a unique calcium
      agonist. SUMMARY: Rotavirus is now a commonly occurring vaccine-preventable
      disease among children in developed countries and hopefully this also will soon
      be true for developing countries. Future studies will determine whether other
      methods of prevention, such as nonreplicating vaccines and antiviral drugs, will
      be needed to treat disease in immunocompromised children.

PMID- 19114773
TI  - NSAIDs and the colon.
AB  - PURPOSE OF REVIEW: To better understand the effects of NSAIDs on the colon.
      RECENT FINDINGS: An epidemiological study has confirmed that NSAIDs increase the
      risk of hospitalizations for lower gastrointestinal complications, though the
      estimated rate of hospitalization was lower than that for upper gastrointestinal
      complications. Proton-pump inhibitors were associated with reduction in
      hospitalizations for upper but not lower gastrointestinal complications. Current
      research on cyclooxygenase (COX) inhibition in patient and animal models suggests
      that COX-1 and COX-2 may have different roles in the exacerbation of inflammatory
      bowel disease. Epidemiological research on the chemoprevention of colorectal
      cancer with aspirin suggests that the positive effect of risk reduction is only
      observed after long-term treatment. The search for targets of chemopreventive
      drugs is ongoing. COX-2 inhibition still seems preferred option, as the effects
      observed with aspirin (the only chemopreventive agent with some apparent future)
      are more profound only in tumors and cells expressing COX-2. Other molecules such
      as nitric oxide NSAIDs, especially nitric oxide aspirin, are under intensive
      experimental research. SUMMARY: NSAID use increases the risk of hospitalizations
      due to complications in the lower gastrointestinal tract. By inhibiting COX-2 or
      other tumorigenic targets, NSAIDs, especially aspirin or new aspirin derivates,
      may prevent colon cancer in selected populations.

PMID- 19114774
TI  - Computed tomographic colonography.
AB  - PURPOSE OF REVIEW: Computed tomographic colonography is a new and noninvasive
      method to evaluate the colon. The goal of this review is to discuss the latest
      data and define outstanding issues related to computed tomographic colonography.
      RECENT FINDINGS: Computed tomographic colonography is gaining momentum as a
      potential primary colon cancer screening method in the USA. Although not as
      accurate as colonoscopy, the accuracy of computed tomographic colonography for
      detection of large lesions appears to be in the 80-90% range. The field is
      rapidly evolving, not only in terms of technology but also in a variety of other
      practical areas. SUMMARY: Current data suggest that computed tomographic
      colonography is a viable colon cancer screening modality in the USA. However, it
      is not ready for widespread implementation, largely because of lack of standards
      for training and reading and the fact that the number of skilled readers is
      limited.

PMID- 19114775
TI  - Aberrant crypt foci: are they intermediate endpoints of colon carcinogenesis in
      humans?
AB  - PURPOSE OF REVIEW: There is a wealth of literature, both from epidemiological and
      molecular studies, which support the role of aberrant crypt foci (ACF) as a
      putative precursor to colorectal adenomas and a potential biomarker for
      colorectal carcinoma. In this review, we critically examine the evidence on
      employing ACF as an intermediate endpoint. RECENT FINDINGS: Recent, larger-scale,
      multicenter studies of ACF have raised questions about ACF. The prevalence of ACF
      has not correlated with colorectal adenomas, and the technique for ACF detection
      using high-magnification chromoendoscopy has demonstrated considerable
      variability across endoscopists and over time. Dysplastic ACF, once postulated as
      the ACF destined for adenomatous transformation, have been rarely identified in
      US individuals, in contrast to European and Japanese investigations. A
      substantial percentage of purported, endoscopically detected ACF have not been
      confirmed on histologic review. Finally, molecular characterization of ACF has
      been studied on only a limited basis. SUMMARY: ACF remain a potential biomarker
      for colorectal cancer, but similar to other biomarkers under development,
      additional study of ACF is needed before reliable, clinical application can be
      assured.

PMID- 19114776
TI  - Current Opinion in Gastroenterology. Current world literature.

PMID- 19114780
TI  - Palliative care in heart failure: a case study of collaborative practice.

PMID- 19114783
TI  - SHOW ME: enhancing OASIS functional assessment.

PMID- 19114784
TI  - Delirium at home: strategies for home health clinicians.
AB  - Delirium is a challenging, under-appreciated problem in the home care setting.
      When it is not detected early and managed effectively, delirium adversely affects
      outcomes and quality of life. Home healthcare nurses play a key role in the
      assessment, early identification, and management of delirium and in the support
      and education of patients and their family caregivers. This article reviews
      delirium and describes strategies for detecting and managing delirium in the home
      care setting.

PMID- 19114785
TI  - Care of technology-dependent children in the home.
AB  - Home care for infants and children requiring life-sustaining technological
      interventions has been a common alternative to long-term hospitalization since
      the early 1980s. This has created a need for a sufficient pool of competent home
      health clinicians capable of providing highly skilled care in the home and of
      supporting family caregivers. The Pennsylvania Ventilator-Assisted Children's
      Home Program (VACHP) has developed and successfully implemented a 32-hour
      training program that has equipped more than 300 clinicians with the knowledge
      and skill level necessary to provide competent care for these children.

PMID- 19114786
TI  - Challenges in caring for morbidly obese patients.
AB  - This study aimed to determine how morbidly obese patients and their families
      manage activities of daily living (ADLs) at home. A survey design was used for
      this descriptive study. Home healthcare professionals identified both challenges
      and innovations in managing the ADLs of the morbidly obese in the home.

PMID- 19114788
TI  - Literacy and healthcare: the challenge of communication in home healthcare and
      hospice.

PMID- 19114789
TI  - Model for consideration: retaining the experienced aging workforce in home care.
AB  - As the nursing workforce in the United States ages, home health agencies must
      step up efforts to retain their experienced and mature nurses. Satisfying
      positions for the aging experienced nursing workforce are lacking. The model for
      consideration has 3 levels of nursing practice, including those of nurse case
      managers, comprehensive data assessment nurses, and visiting nurses.

PMID- 19114790
TI  - Home healthcare nurses and clinicians can bring significant savings to the table.

PMID- 19114791
TI  - Remembering Lillian Wald: remembering our roots.

PMID- 19114794
TI  - Commentary on "Depression and anxiety symptoms are associated with reduced
      dietary adherence in patients with heart failure treated with an implantable
      cardioverter defibrillator".

PMID- 19114795
TI  - Depression and anxiety symptoms are associated with reduced dietary adherence in
      heart failure patients treated with an implantable cardioverter defibrillator.
AB  - BACKGROUND: Heart failure (HF) patients treated with an implantable cardioverter
      defibrillator (ICD) are a growing patient population for whom the general
      treatment guidelines for HF still apply. Dietary recommendations, sodium and
      fluid restriction and daily weight monitoring, are a critical component of HF
      self-management. However, HF patients often report poor adherence to these
      recommendations. Studies that have investigated factors associated with poor diet
      adherence have focused on knowledge and beliefs. The current study extends
      previous research by examining the impact of psychosocial factors (depression,
      anxiety, and social support) on adherence to dietary recommendations in this
      growing subgroup of HF patients. METHODS: Eighty-eight HF patients, with a mean
      age of 70 years, treated with an ICD (77% male) completed questionnaires
      assessing depression and anxiety symptoms, social support, and dietary adherence.
      RESULTS: Most patients reported following dietary recommendations in the past
      week most of the time (63%), whereas only 16% of patients reported following
      dietary recommendations all of the time. Greater depression and anxiety symptoms
      were associated with poorer dietary adherence, whereas social support did not
      predict reported dietary adherence. CONCLUSIONS: Findings suggest that many HF
      patients treated with an ICD do not comply with dietary recommendations.
      Depression and anxiety symptoms were found to be associated with worse dietary
      adherence, whereas social support was not related to adherence. Further research
      is needed to understand the role of social support in dietary adherence in HF
      patients.

PMID- 19114796
TI  - Progress in prevention: should we screen for risk factors or disease? A current
      debate in the prevention of cardiovascular events.

PMID- 19114799
TI  - A qualitative study of the psychological experience of patients during and after
      mechanical cardiac support.
AB  - OBJECTIVES: Treatments for end-stage heart failure include medical therapy, heart
      transplantation, and, more recently, implantation of a ventricular support assist
      device (VAD). Little is known about the psychological adjustment and quality of
      life of these patients and how patients with a VAD in situ compare with those who
      underwent transplantation or had the device explanted. DESIGN AND METHODS: A
      cross-sectional study using grounded theory methodology was carried out. Patients
      with heart failure living with a VAD and those who underwent transplantation or
      explantation were interviewed to elicit perceptions of their adjustment and
      quality of life. RESULTS: All patients identified perceived control as their core
      category, with 3 related conceptual categories: normality, uncertainty, and
      emotional state. Identity of illness/VAD and the impact of the device were
      specifically identified by VAD patients, and independence was identified by
      transplant patients. CONCLUSION: This study has identified previously
      unrecognized concepts in the adjustment of patients with either a VAD in situ or
      who have had the device explanted or have undergone transplantation. It provides
      a basis for the development of specific nursing and psychological care designed
      to support this developing surgical practice.

PMID- 19114797
TI  - Predictors of implantable cardioverter defibrillator shocks during the first
      year.
AB  - The purpose of this study was to predict implantable cardioverter defibrillator
      (ICD) shocks using demographic and clinical characteristics in the first year
      after implantation for secondary prevention of cardiac arrest. A prospective
      design was used to follow 168 first-time ICD recipients over 12 months.
      Demographic and clinical data were obtained from medical records at the time of
      ICD insertion. Implantable cardioverter defibrillator shock data were obtained
      from ICD interrogation reports at hospital discharge, 3, 6, and 12 months.
      Logistic regression was used to predict ever receiving an ICD shock using
      background characteristics. Patients received an ICD for secondary prevention of
      sudden cardiac arrest, they were 64.1 years old, 89% were white, 77% were male,
      with a mean (SD) ejection fraction of 33.7% (14.1%). The cumulative percentage of
      ever receiving an ICD shock was 33.3% over 1 year. Three variables predicted
      shocks in the first year: history of chronic obstructive pulmonary disease (COPD)
      (odds ratio [OR], 4.42; 95% confidence interval [CI], 1.2-16.4; P = .03), history
      of congestive heart failure (OR, 3.55; 95% CI, 1.4-9.3; P = .01), and documented
      ventricular tachycardia (VT) at the time of ICD implant (OR, 10.05; 95% Cl, 1.8
      55.4; P = .01). High levels of anxiety approached significance (OR = 2.82; P =
      .09). The presence of COPD, congestive heart failure, or VT at ICD implant was a
      significant predictor of receiving an ICD shock in the first year after ICD
      implantation. Because ICD shocks are distressing, painful, and associated with
      greater mortality, healthcare providers should focus attention on prevention of
      shocks by controlling VT, careful management of HF symptoms, reduction of the use
      of short acting beta agonist medications in COPD, and perhaps recognizing and
      treating high levels of anxiety.

PMID- 19114800
TI  - Determinants of self-care behaviors in community-dwelling patients with heart
      failure.
AB  - BACKGROUND AND RESEARCH OBJECTIVE: As the population ages, chronic conditions
      such as heart failure are becoming more prevalent. An important goal is to
      understand how patients with heart failure learn to manage the often debilitating
      disease symptoms. The research objective was to examine the determinants of
      general and therapeutic self-care behaviors among community-dwelling heart
      failure patients. Guided by Connelly's Model of Self-care in Chronic Illness,
      enabling and predisposing factors were evaluated using sociodemographic
      characteristics, functional ability, and psychological status. Self-care
      maintenance, self-efficacy, and self-care management characteristics were also
      evaluated. PARTICIPANTS AND METHODS: Using a cross-sectional design, a
      convenience sample of 65 ambulatory care patients were recruited. Data were
      collected through chart reviews and questionnaires. RESULTS AND CONCLUSIONS:
      Common self-care maintenance behaviors included taking medication as prescribed
      (95%), seeking physician guidance (80%), and following sodium dietary
      restrictions (70%). These behaviors were influenced by enabling characteristics
      such as psychological status (P = .030), ethnicity (P = .048), and comorbidity (P
      = .023). A unique finding was that self-care maintenance behaviors were
      significantly lower in aboriginal participants. The predisposing characteristic
      of self-efficacy influenced self-maintenance behaviors (P = .0002), overall self
      care (P = .04) and number of hospital admissions (P < .0001). Higher overall self
      care scores, measured by the summative Self-care Heart Failure Index score was
      correlated with fewer hospital admissions (P = .019).

PMID- 19114801
TI  - Commentary: "Explicating nurses' cardiac triage decisions".

PMID- 19114802
TI  - Explicating nurses' cardiac triage decisions.
AB  - BACKGROUND AND RESEARCH OBJECTIVE: Although nurses frequently determine patient
      priority and urgency status for emergency evaluation and treatment of symptoms
      suggestive of myocardial infarction (MI), surprisingly few studies have
      specifically examined the cardiac triage decisions of emergency department (ED)
      nurses. Therefore, the purpose of this study was to explicate the decision-making
      processes of ED nurses who triage men and women for MI. SUBJECTS AND METHODS: A
      qualitative, descriptive study was conducted using focus group methodology. A
      synthesized conceptual model was used to guide focus group discussions and to
      begin the process of developing a conceptually based, quantifiable measure of ED
      nurses' cardiac triage decisions. Participants' (N = 12) oral descriptions were
      audiotape recorded, transcribed verbatim, and analyzed using the Krueger content
      analysis method. RESULTS: When making MI triage decisions and determining triage
      urgency status, ED nurses determine the underlying cause of patients' chief
      complaints based on clinical presentation, patient demographics, past medical
      history, as well as their own attitudes, perceptions and beliefs, nursing
      knowledge, and ED experience. Important patient cues include general appearance,
      vital signs, cardiac history, chest pain, and mode of transportation. Nurse's
      ultimate goal when making cardiac triage decisions is to have the patient receive
      a prompt electrocardiogram and prompt medical evaluation and to advocate for the
      patient. CONCLUSIONS: Nurses are knowledgeable of age and sex differences in MI
      presentation. However, some nurses hold cultural biases and stereotypes that may
      interfere with the timely delivery of emergency cardiac healthcare. Findings from
      this study will be used to develop a quantifiable measure of ED nurses' cardiac
      triage decision-making processes.

PMID- 19114810
TI  - Managing vascular access device occlusions, part 1.

PMID- 19114814
TI  - Procedure trays: a call to action for sharps safety.

PMID- 19114815
TI  - A closer look at coccidioidomycosis.

PMID- 19114803
TI  - Randomized clinical trials of weight loss maintenance: a review.
AB  - The problem of overweight and obesity has reached epidemic proportions in the
      United States and globally, and the high prevalence is due in part to the
      recidivism associated with weight loss treatment. Approximately one-third of lost
      weight is often regained in the first year after treatment and, at times,
      continues. Because a plethora of comorbid diseases are associated with obesity,
      in particular, cardiovascular disease, hypertension, and hyperlipidemia,
      clinicians and researchers have attempted to find useful strategies for
      maintaining weight loss. This review presents the findings from 42 randomized
      clinical trials of weight loss maintenance from 1984 through 2007 using
      interventions that include (1) the Internet, (2) strategies after a very low
      calorie diet, (3) pharmacotherapy, (4) behavioral strategies, (5) physical
      activity, and (6) alternative strategies. The results of the reviewed trials
      revealed that treatment with orlistat or sibutramine combined with dietary
      modification, caffeine or protein supplementation, consuming a diet lower in fat,
      adherence to physical activity routines, prolonged contact with participants,
      problem-solving therapy, and the alternative treatment of acupressure were
      efficacious in reducing weight regain after weight loss treatment. The
      limitations of some studies may reduce the robustness of their findings, and
      future studies are necessary to replicate and support these results so that
      individuals are able to maintain weight loss and retain the health benefits
      associated with a lower weight.

PMID- 19114816
TI  - Using a mummy restraint.

PMID- 19114820
TI  - Sidestepping unsafe abbreviations.

PMID- 19114821
TI  - How often do patients need tetanus prophylaxis?

PMID- 19114831
TI  - Consider the ethical issues raised by organ donation, such as how to define
      death. Then examine your own opinions.

PMID- 19114832
TI  - Shedding health risks with bariatric weight loss surgery.
AB  - More and more obese patients are turning to bariatric weight loss surgery, which
      is proving its worth by decreasing or eliminating dangerous comorbidities of
      obesity. Here's how to help prepare your patient for surgery and care for her
      afterward.

PMID- 19114834
TI  - Putting a stop to dysfunctional uterine bleeding.
AB  - Learn how to search for the source of abnormal bleeding and help your patient get
      back on track.

PMID- 19114836
TI  - Unlocking the secrets of 2 common cardiac conditions.
AB  - Find out about the latest guidelines for unstable angina and non-ST-segment
      elevation myocardial infarction.

PMID- 19114837
TI  - The light of life.
AB  - Two early experiences shape a young nurse's perspective on the mystery of death.

PMID- 19114838
TI  - Patient education series. How to manage your asthma.

PMID- 19114839
TI  - Take steps to prevent pressure ulcers.

PMID- 19114841
TI  - . . . About sleep.

PMID- 19114842
TI  - Transfusion reaction.

PMID- 19114843
TI  - If change is the buzz, what can it mean for us?

PMID- 19114844
TI  - An update on antithrombotic guidelines.

PMID- 19114846
TI  - Fluoroquinolone-induced tendinopathy.

PMID- 19114847
TI  - Legislative update 2009: despite legal issues, APNs are still standing strong.

PMID- 19114848
TI  - Assessing & managing female sexual dysfunction.

PMID- 19114850
TI  - Female sexual dysfunction.

PMID- 19114852
TI  - Efficacy and safety of etravirine (TMC125) in treatment-experienced HIV-1
      infected patients: 48-week results of a phase IIb trial.
AB  - Forty-eight-week results from a randomized, multicentre, part-blinded, phase IIb
      clinical trial assessing the efficacy and safety of 400 and 800 mg etravirine
      twice daily (phase IIb formulation) and optimized background regimen versus
      standard-of-care regimen are presented. Both etravirine doses demonstrated
      sustained virological suppression at 48 weeks and a favourable tolerability
      profile. Etravirine demonstrated higher efficacy than control, irrespective of
      the number of detectable nonnucleoside reverse transcriptase inhibitor-resistance
      associated mutations at baseline or active background antiretrovirals.

PMID- 19114853
TI  - Is the time for an AIDS-free new generation different in resource-limited and
      industrialized countries?

PMID- 19114854
TI  - HIV monotherapy with ritonavir-boosted protease inhibitors: a systematic review.
AB  - OBJECTIVE: To assess the efficacy of ritonavir-boosted protease inhibitor
      monotherapy. DESIGN AND METHODS: Systematic review of all protease inhibitor
      monotherapy studies published in peer-reviewed journals or presented at
      conferences to date. Data of randomized controlled trials were pooled to yield
      common odds ratios. RESULTS: Twenty-two protease inhibitor-monotherapy studies
      were identified. In the intent-to-treat analysis, 395 out of 582 (67.9%) patients
      had undetectable HIV-RNA at the end of follow-up. In the six randomized
      controlled trials (all lopinavir/ritonavir monotherapy), the risk of therapy
      failure was greater on monotherapy: 121 out of 364 (33.2%) patients on
      monotherapy against 64 out of 280 (22.9%) patients on HAART [pooled odds ratio
      1.48 (95% confidence interval 1.02-2.13, P = 0.037)]. Regarding patients with
      successfully resuppressed HIV-RNA upon (re-)introducing nucleoside reverse
      transcriptase inhibitors (NRTIs) as nonfailures, the risk of therapy failure was
      comparable: 98 out of 364 (26.9%) against 64 out of 280 (22.9%) patients [odds
      ratio 1.05 (95% confidence interval 0.72-1.53, P = 0.81)]. CONCLUSION: The
      overall efficacy of ritonavir-boosted protease inhibitor monotherapy is inferior
      to HAART. The efficacy improves in patients started on monotherapy after
      suppressed HIV-RNA for at least 6 months. Ten percent of patients have viral
      rebound with HIV-RNA levels between 50 and 500 copies/ml. Possible explanations
      are lack of HIV suppression in particular cells or compartments, alternative
      resistance mechanisms, and nonadherence. Once proven that reintroduction of
      NRTIs, in patients with loss of viral suppression, is safe and effective, a
      broader use of simplification of HAART to protease inhibitor monotherapy might be
      justified. This review supports that the majority of patients with prolonged
      viral suppression on HAART can successfully be treated with protease inhibitor
      monotherapy. Arguments for this strategy are NRTI/NNRTI side effects, NRTI/NNRTI
      resistance, and costs.

PMID- 19114855
TI  - Efficacy and tolerability of initial antiretroviral therapy: a systematic review.
AB  - OBJECTIVES: Successful antiretroviral therapy (ART) is largely attributed to the
      type of third drug. Guidelines recommend regimens without systematic review of
      all factors that might affect treatment success, such as study design,
      eligibility criteria and participant characteristics. Why patients cease ART has
      not been systematically studied. DESIGN AND SETTING: Systematic review of initial
      ART studies (64 randomized, 15 cohort). Group-based analysis was by weighted,
      forward, stepwise, linear regression. MAIN OUTCOME MEASURES: Treatment efficacy
      (undetectable plasma HIV viral load by intention-to-treat) and cessation for
      adverse events. RESULTS: Seven variables were independently associated with study
      groups reporting higher treatment success (mean 59%, r = 0.79): nonwhite race (P
      = 0.002), exclusion for low haemoglobin (P = 0.0006), lower CD4 cell count (P =
      0.014), dosing relative to food (P = 0.001), dual-nucleoside backbone (favouring
      didanosine or tenofovir with emtricitabine or lamivudine; P = 0.002),
      nonnucleoside analogue or ritonavir-boosted protease inhibitor as the third drug
      (P < 0.0001), and shorter follow-up (P = 0.0004). Although the most common cause
      of treatment cessation (9.0%), adverse events were reported in only half of
      studies and were significantly more likely in studies that were phase 2 or 3,
      academia-sponsored and less than 36 months duration, and in older participants.
      Nausea was the only adverse event significantly associated with treatment success
      (r = -0.277). CONCLUSION: Multiple reasons influence initial ART success beyond
      the type of third drug and should be considered when designing and comparing
      studies. Most studies are too short and report insufficient adverse event data.
      Didanosine is an effective option for initial ART, with particular relevance to
      resource-limited settings. ART guideline development might benefit from
      systematic review.

PMID- 19114856
TI  - Delayed loss of control of plasma lipopolysaccharide levels after therapy
      interruption in chronically HIV-1-infected patients.
AB  - OBJECTIVE: Increased circulating levels of lipopolysaccharide (LPS) have been
      demonstrated in HIV-1-infected progressors. We investigated the effect of
      antiretroviral therapy (ART) interruptions on plasma LPS levels. DESIGN AND
      METHODS: Overall, 77 individuals participated in this study (51 HIV-positive and
      26 healthy). Ten out of 51 HIV-positive participants were viremic ART-naive
      patients and 41 out of 51 were chronically suppressed patients on ART (three or
      more drugs, CD4 cell count more than 400 cells/microl, HIV-1 RNA less than 500
      copies/ml for more than 8 months, less than 50 copies/ml at recruitment)
      undergoing therapy interruption. The limulus amebocyte assay was used to measure
      plasma LPS levels; enzyme-linked immunosorbent assay to measure plasma levels of
      endotoxin-core antibodies (EndoCAb), soluble (s)CD14, LPS-binding protein and IFN
      alpha; immunoblotting to measure plasma gelsolin levels; and same day whole blood
      flow cytometry to measure levels of T-cell-activation markers (CD8/CD38, CD8/HLA
      DR and CD3/CD95). RESULTS: Increases in viremia and T-cell-activation markers
      were observed during therapy interruptions. During short-term therapy
      interruptions of less than 12 weeks, no change in LPS levels was found, whereas
      negative associations between viral load and LPS levels (Spearman's Rho = -0.612,
      P = 0.0152), viral load and EndoCAb change (DeltaEndoCAb, correlation = -0.502, P
      = 0.0204), and between DeltaLPS and DeltaEndoCAb (correlation = -0.851, P =
      0.0073) were observed. In contrast, increased LPS (P = 0.0171) and sCD14 (P <
      0.0001) levels were observed during long-term therapy interruption of more than
      12 weeks compared with levels during ART, together with no association between
      LPS and viral load or EndoCAb. No association between immune activation and LPS
      was evident at any time point. CONCLUSION: Increased plasma LPS levels were
      observed only after more than 12 weeks of ART interruption, despite presence of
      LPS-controlling host mechanisms.

PMID- 19114857
TI  - Elevated levels of vitamin B12 and folate in vertically infected children with
      HIV-1.
AB  - OBJECTIVE: Neurologic and hematologic abnormalities are common in HIV-infected
      children and may be related to concomitant deficiencies in serum B12 and folate,
      which are highly prevalent in HIV-infected adults. We sought to determine the
      prevalence of B12 and folate deficiencies in HIV-infected children in the United
      States. METHODS: Cross-sectional information on demographics, folate and B12
      levels, hematological parameters, concurrent CD4%, HIV-viral load and
      antiretroviral regimens were abstracted from the medical records of 103
      vertically infected children followed in an outpatient pediatric HIV clinic in
      the Bronx, during 2001-2002. RESULTS: Mean age was 10 years (+/-4.4 years), 46%
      were male, 53% African-American and 46% Hispanic. Nineteen percent had
      significant immunologic suppression and 18 children had AIDS. All were receiving
      combination antiretroviral therapy and 66% were on a protease inhibitor-based
      regimen. Sixteen were taking cotrimoxazole prophylaxis. None were taking
      multivitamins or manifested clinical evidence of gastrointestinal malabsorption.
      All patients had serum folate or B12 levels within or above the normal range.
      Children with elevated B12 were significantly more likely to be younger (P =
      0.0002) and have higher mean folate levels (P = 0.0004) compared with children
      with normal serum B12. In a multivariate logistic regression analysis, factors
      independently associated with elevated levels of vitamin B12 included: elevated
      serum folate [odds ratio (OR): 3.2; P = 0.01], nonnucleoside reverse
      transcriptase inhibitor use (OR: 0.38; P = 0.05) and female sex (OR: 0.67; P =
      0.42) CONCLUSION: Folate and B12 deficiencies are uncommon in HIV-infected
      children in the United States, suggesting that routine supplementation with B12
      and folate is not indicated without confirmation of micronutrient deficiency.

PMID- 19114858
TI  - HIV prevalence and risk behaviour among men who have sex with men in Vientiane
      Capital, Lao People's Democratic Republic, 2007.
AB  - BACKGROUND: Men who have sex with men are at high risk for HIV infection. Here we
      report the results of the first assessment of HIV prevalence and risk behaviour
      in this group in Vientiane, Lao People's Democratic Republic. METHODS: Between
      August and September 2007, 540 men were enrolled from venues around Vientiane,
      using venue-day-time sampling. Men of Lao nationality, 15 years and over,
      reporting oral or anal sex with a man in the previous 6 months were eligible for
      participation. Demographic and socio-behavioural information was self-collected
      using hand-held computers. Oral fluid was tested for HIV infection. Logistic
      regression was used to evaluate risk factors for prevalent HIV infection.
      RESULTS: The median age of participants was 21 years; the HIV prevalence was
      5.6%. Of participants, 39.6% reported exclusive attraction to men and 57.6%
      reported sex with women. Of those who reported having regular and nonregular
      sexual partner(s) in the past 3 months, consistent condom use with these partners
      was 14.4 and 24.2%, respectively. A total of 42.2% self-reported any sexually
      transmitted infection symptoms and 6.3% had previously been tested for HIV.
      Suicidal ideation was reported by 17.0%, which was the only variable
      significantly and independently associated with HIV infection in multivariate
      analysis. CONCLUSION: Although the HIV prevalence is low compared with
      neighbouring countries in the region, men who have sex with men in Lao People's
      Democratic Republic are at high behavioural risk for HIV infection. To prevent a
      larger HIV epidemic occurrence and transmission into the broader community,
      higher coverage of HIV prevention interventions is required.

PMID- 19114859
TI  - Risk factors for HIV incidence in women participating in an HSV suppressive
      treatment trial in Tanzania.
AB  - OBJECTIVES: A randomized, double-blind, placebo-controlled trial (RCT) of herpes
      simplex virus type 2 suppressive therapy with acyclovir 400 mg twice daily
      conducted among women in northwestern Tanzania reported a similar rate of HIV
      acquisition in both trial arms (Current Controlled Trials number ISRCTN35385041).
      Risk factors for HIV incidence were examined in the context of 3-monthly follow
      up visits offering both voluntary counselling and testing and care for sexually
      transmitted infections. DESIGN: Prospective cohort analysis of trial participants
      enrolled and followed for up to 30 months. METHODS: Risk factors for HIV
      acquisition were analysed using Cox regression. RESULTS: Overall, 821 herpes
      simplex virus type 2 seropositive, HIV seronegative women were randomized; 400
      randomized to acyclovir and 421 to placebo; 659 (80.3%) completed follow-up. HIV
      incidence was 4.27 per 100 person-years. There was no overall impact of acyclovir
      on HIV incidence [hazard ratio = 1.01; 95% confidence interval (CI) 0.61-1.66].
      HIV acquisition was independently associated with younger age at enrolment (age
      16-19 vs. 30-35: hazard ratio = 4.02; 95% CI 1.67-9.68), alcohol consumption at
      enrolment (> or =30 drinks/week vs. none: hazard ratio = 4.39, 95% CI 1.70
      11.33), having paid sex within the previous 3 months (hazard ratio = 1.82, 95% CI
      1.09-3.05), recent infection with gonorrhoea (hazard ratio = 3.62, 95% CI 1.62
      8.08) and injections in the previous 3 months (hazard ratio = 3.45, 95% CI 1.62
      7.34). There was some evidence of an association between HIV incidence and living
      in the recruitment community for less than 2 years (hazard ratio = 1.75, 95% CI
      0.98-3.10) and exposure to hormonal contraception (hazard ratio = 1.60, 95% CI
      0.93-2.76). CONCLUSION: A high incidence of HIV was observed in this trial
      cohort, especially in young women. Interventions are needed to address the risk
      associated with alcohol use and to sustain control of other sexually transmitted
      infections.

PMID- 19114861
TI  - Oral HIV-exposure elicits mucosal HIV-neutralizing antibodies in uninfected men
      who have sex with men.
AB  - OBJECTIVE: To determine whether oral sexual exposure to HIV-1 (HIV) results in
      HIV-neutralizing activity in saliva of uninfected men who have sex with infected
      men? DESIGN: Saliva samples were collected from HIV IgG seronegative men (n = 25)
      whose male partners were HIV infected and from low-risk healthy controls (n = 22)
      and analyzed for HIV-neutralizing capacity. METHODS: The presence of neutralizing
      activity in saliva was tested in a peripheral blood mononuclear cell-based assay
      using primary HIV isolates. Self-reporting questionnaires described the
      individuals' sexual behaviors and routes of possible HIV exposure. RESULTS: Of 25
      exposed, uninfected individuals (EUI), 21 reported receptive unprotected oral
      intercourse, whereas three of the 25 reported unprotected anal receptive
      intercourse. Whole saliva from both EUI and low-risk healthy controls contained
      HIV-neutralizing activity. However, a significant difference was seen when
      analyzing the salivary IgA1 fraction: 13 of 25 EUI neutralized HIV, whereas none
      of the 22 controls had this capacity. The neutralizing capacity of the EUI males
      persisted during 2 years of follow-up. CONCLUSION: Unprotected oral sex evokes a
      salivary IgA1-mediated HIV-neutralizing response that persists over time during
      continuous exposure in uninfected male partners of infected men.

PMID- 19114860
TI  - A randomized trial of therapeutic drug monitoring of protease inhibitors in
      antiretroviral-experienced, HIV-1-infected patients.
AB  - OBJECTIVE: Whether therapeutic drug monitoring of protease inhibitors improves
      outcomes in HIV-infected patients is controversial. We evaluated this strategy in
      a randomized, open-label clinical trial, using a normalized inhibitory quotient
      (NIQ), which incorporates drug exposure and viral drug resistance. NIQs < or = 1
      may predict poor outcome and identify patients who could benefit from dose
      escalation. DESIGN/METHODS: Eligible patients had a viral load > or =1000
      copies/ml on a failing regimen, and began a new protease inhibitor containing
      regimen at entry. All FDA-approved protease inhibitors available during the study
      recruitment (June 2002-May 2006) were allowed. One hundred and eighty-three
      participants with NIQ < or = 1, on the basis of their week 2 protease inhibitor
      trough concentration and pre-entry drug resistance test, were randomized at week
      4 to standard of care (SOC) or protease inhibitor dose escalation (TDM). The
      primary endpoint was change in log10 plasma HIV-1 RNA concentration from
      randomization to 20 weeks later. RESULTS: Ninety-one patients were randomized to
      SOC and 92 to TDM. NIQs increased more in the TDM arm compared to SOC (+69 versus
      +25%, P = 0.01). Despite this, TDM and SOC arms showed no difference in outcome
      (+0.09 versus +0.02 log10, P = 0.17). In retrospective subgroup analyses,
      patients with less HIV resistance to their protease inhibitors benefited from TDM
      (P = 0.002), as did black and Hispanic patients (P = 0.035 and 0.05,
      respectively). Differences between black and white patients persisted when
      accounting for protease inhibitor susceptibility. CONCLUSIONS: There was no
      overall benefit of TDM. In post hoc subgroup analyses, TDM appeared beneficial in
      black and Hispanic patients, and in patients whose virus retained some
      susceptibility to the protease inhibitors in their regimen.

PMID- 19114862
TI  - Multidrug-experienced HIV-1-infected women demonstrated similar virological and
      immunological responses to tipranavir/ritonavir compared with men.
AB  - Gender-related differences in the efficacy and safety of ritonavir-boosted
      tipranavir [tipranavir/ritonavir (TPV/r) 500/200 mg twice daily (b.i.d.)] were
      evaluated in a subanalysis of the Randomized Evaluation of Strategic Intervention
      in Multidrug Resistant Patients with Tipranavir (RESIST) trials. Data from HIV-1
      infected women (203; TPV/r = 117) and men (1280; TPV/r = 629) showed no
      significant gender-related differences in HIV RNA response rates (at 48 weeks)
      and safety (at 96 weeks) despite higher mean steady-state plasma TPV trough
      concentrations in women. Significantly greater increases in CD4 cell count (+81.2
      vs. +48.6; P = 0.0012) were observed in women at week 48.

PMID- 19114863
TI  - A frequent functional toll-like receptor 7 polymorphism is associated with
      accelerated HIV-1 disease progression.
AB  - OBJECTIVES: Toll-like receptors (TLRs) play an important role in the innate
      immune response to pathogens. TLR7 recognizes RNA of various viruses including
      HIV. The objective of this study was to examine the influence of individual
      genetic variations of TLR7 on the susceptibility to and progression of HIV
      disease. METHOD: We genotyped a population of 734 HIV-positive adults and 545
      healthy controls for three TLR7 single nucleotide polymorphisms. The frequency of
      TLR7 genetic variations was assessed and related to HIV disease progression.
      Furthermore, we analyzed peripheral blood mononuclear cells obtained from healthy
      individuals differing in their TLR7 genotype and assessed their response to a
      TLR7-specific ligand ex vivo. RESULTS: Presence of the most frequent TLR7
      polymorphism, TLR7 Gln11Leu, was associated with higher viral loads and
      accelerated progression to advanced immune suppression in HIV patients.
      Furthermore, in women this polymorphism may be associated with increased HIV-1
      susceptibility as it was found more frequently among patients as compared with
      controls. Peripheral blood mononuclear cells from polymorphism carriers secreted
      significantly less IFN-alpha following TLR7 activation, whereas IL-6 production
      remained unaltered. CONCLUSION: This is the first report of a functional TLR7
      variant to be associated with susceptibility to and a more severe clinical course
      of HIV-1 disease. These results may have implications for the risk assessment of
      individual patients as well as for HIV-1 therapy and vaccination strategies in
      the future.

PMID- 19114864
TI  - Epidemiology of nonkeratinocytic skin cancers among persons with AIDS in the
      United States.
AB  - OBJECTIVE: Immunosuppression may increase risk for some skin cancers. We
      evaluated skin cancer epidemiology among persons with AIDS. DESIGN: We linked
      data from population-based US AIDS and cancer registries to evaluate risk of
      nonkeratinocytic skin cancers (melanoma, Merkel cell carcinoma, and appendageal
      carcinomas, including sebaceous carcinoma) in 497 142 persons with AIDS. METHODS:
      Standardized incidence ratios (SIRs) were calculated to relate skin cancer risk
      to that in the general population. We used logistic regression to compare risk
      according to demographic factors, CD4 cell count, and a geographic index of
      ultraviolet radiation exposure. RESULTS: From 60 months before to 60 months after
      AIDS onset, persons with AIDS had elevated risks of melanoma (SIR = 1.3, 95%
      confidence interval 1.1-1.4, n = 292 cases) and, more strongly, of Merkel cell
      carcinoma (SIR = 11, 95% confidence interval 6.3-17, n = 17) and sebaceous
      carcinoma (SIR = 8.1, 95% confidence interval 3.2-17, n = 7). Risk for
      appendageal carcinomas increased with progressive time relative to AIDS onset (P
      trend = 0.03). Risk of these skin cancers was higher in non-Hispanic whites than
      other racial/ethnic groups, and melanoma risk was highest among men who have sex
      with men. Melanoma risk was unrelated to CD4 cell count at AIDS onset (P = 0.32).
      Risks for melanoma and appendageal carcinomas rose with increasing ultraviolet
      radiation exposure (P trend <10 and P trend = 10, respectively). CONCLUSION:
      Among persons with AIDS, there is a modest excess risk of melanoma, which is not
      strongly related to immunosuppression and may relate to ultraviolet radiation
      exposure. In contrast, the greatly increased risks for Merkel cell and sebaceous
      carcinoma suggest an etiologic role for immunosuppression.

PMID- 19114865
TI  - The costs and effectiveness of four HIV counseling and testing strategies in
      Uganda.
AB  - OBJECTIVE: HIV counseling and testing (HCT) is a key intervention for HIV/AIDS
      control, and new strategies have been developed for expanding coverage in
      developing countries. We compared costs and outcomes of four HCT strategies in
      Uganda. DESIGN: A retrospective cohort of 84 323 individuals received HCT at one
      of four Ugandan HCT programs between June 2003 and September 2005. HCT strategies
      assessed were stand-alone HCT; hospital-based HCT; household-member HCT; and door
      to-door HCT. METHODS: We collected data on client volume, demographics, prior
      testing and HIV diagnosis from project monitoring systems, and cost data from
      project accounts and personnel interviews. Strategies were compared in terms of
      costs and effectiveness at reaching key population groups. RESULTS: Household
      member and door-to-door HCT strategies reached the largest proportion of
      previously untested individuals (>90% of all clients). Hospital-based HCT
      diagnosed the greatest proportion of HIV-infected individuals (27% prevalence),
      followed by stand-alone HCT (19%). Household-member HCT identified the highest
      percentage of discordant couples; however, this was a small fraction of total
      clients (<4%). Costs per client (2007 USD) were $19.26 for stand-alone HCT,
      $11.68 for hospital-based HCT, $13.85 for household-member HCT, and $8.29 for
      door-to-door-HCT. CONCLUSION: All testing strategies had relatively low per
      client costs. Hospital-based HCT most readily identified HIV-infected individuals
      eligible for treatment, whereas home-based strategies more efficiently reached
      populations with low rates of prior testing and HIV-infected people with higher
      CD4 cell counts. Multiple HCT strategies with different costs and efficiencies
      can be used to meet the UNAIDS/WHO call for universal HCT access by 2010.

PMID- 19114866
TI  - Immunovirological and therapeutic follow-up of HIV-1/HIV-2-dually seropositive
      patients.
AB  - Among the 3700 HIV-infected patients followed in our institution, 17 with regular
      clinical, immunological and virological follow-up and identified as being dually
      seropositive for HIV-1 and HIV-2 were included in this study. Antiretroviral
      therapy seemed to be as effective, in terms of virological and immunological
      response, as in patients infected by HIV-1 alone. Nevertheless, the observed
      selection of HIV-2 protease resistance mutations in two cases underlines the
      importance of selecting drugs that are active on both viruses.

PMID- 19114868
TI  - Levels of innate immune factors in genital fluids: association of alpha defensins
      and LL-37 with genital infections and increased HIV acquisition.
AB  - BACKGROUND: Several mucosal innate immune proteins exhibit HIV inhibitory
      activity and their analogues are potential microbicide candidates. However, their
      clinical associations and in-vivo role in cervicovaginal host defense against HIV
      acquisition are poorly defined. METHODS: Cervicovaginal secretions (CVSs) were
      collected from HIV uninfected Kenyan sex workers at enrolment into an HIV
      prevention trial. After trial completion, CVS from participants acquiring HIV
      (cases) and matched controls were assessed for levels of innate immune factors
      and HIV neutralizing capacity, by blinded investigators. Cross-sectional and
      prospective associations of innate immune factors were examined. RESULTS: CVS
      contained high levels of defensins (human neutrophil peptide-1-3 and human beta
      defensin-2-3), LL-37 and secretory leukocyte protease inhibitor. Regulated upon
      activation normal T-cell expressed and secreted levels were lower, and IFNalpha
      was undetectable. CVS from 20% of participants neutralized a clade A primary HIV
      isolate, and 12% neutralized both clade A and C isolates. HIV neutralization was
      correlated with human neutrophil peptide-1-3 (alpha-defensins) and LL-37 levels.
      However, alpha-defensin and LL-37 levels were increased in participants with
      bacterial sexually transmitted infections and were independently associated with
      increased HIV acquisition in multivariate analysis. CONCLUSIONS: Despite
      significant HIV inhibitory activity, cervicovaginal levels of alpha-defensins and
      LL-37 were associated with increased HIV acquisition, perhaps due to their
      association with bacterial sexually transmitted infections.

PMID- 19114867
TI  - HIV-1 infection of human penile explant tissue and protection by candidate
      microbicides.
AB  - OBJECTIVE: Factors governing events between exposure of male genital mucosa
      surfaces and the establishment of infection are poorly understood. Furthermore,
      little is known about the safety and efficacy of microbicides on male genital
      mucosa. DESIGN: Here we present a novel penile tissue explant model to
      characterize the mechanisms of HIV-1 infection of male genital tissue and
      evaluate candidate microbicides. METHODS: Mucosal explant culture conditions were
      determined for glans, urethra and foreskin obtained from gender reassignment and
      circumcision. Density and distribution of CD4 and CD1a cells were visualized by
      microscopy. In vitro HIV-1 infection was determined by measuring p24 release,
      whereas microbicide biocompatibility and efficacy were assessed by measurement of
      tissue viability, cytokine expression and p24 production. RESULTS: Cultured glans
      and foreskin showed comparable epithelial thickness but some differences in CD4
      and CD1a cell density. All tissue sites examined (foreskin, glans, meatus,
      urethra) were equally susceptible to R5 HIV-1 infection, which was productively
      disseminated by migratory cells emigrating from tissue. In contrast, X4 HIV-1
      failed to infect mucosal tissue and dissemination by migratory cells was less
      efficient. The three candidate microbicides poly(methyl 2-propionamidoacrylate),
      PRO 2000 and Cyanovirin-N, showed good tissue compatibility and efficient
      prevention of HIV-1 infection, causing only minor changes in tissue cytokine
      profile. CONCLUSION: The described model provides a useful model to study the
      determinants of HIV-1 infection of male genital tissue and is likely to be an
      important tool for the future development of microbicide candidates and concepts.

PMID- 19114869
TI  - CD4 cell-guided scheduled treatment interruptions in HIV-infected patients with
      sustained immunologic response to HAART.
AB  - OBJECTIVE: To compare continuous HAART with a CD4 cell-driven scheduled treatment
      interruption (STI) strategy. METHODS: LOng Term Treatment Interruption study is a
      randomized, controlled, prospective trial. Patients with CD4 cell counts more
      than 700 cells/microl were eligible, and the immunologic threshold to resume
      HAART was 350 cells/microl. The primary end point was the development of an
      opportunistic disease, death from any cause or the occurrence of diseases, other
      than opportunistic, requiring hospital admission. Secondary end points were major
      adverse effects, virologic failures and therapeutic costs. RESULTS: Three hundred
      and twenty-nine patients were randomized 1: 1. Total follow-up was 1388 person
      years (mean 4.2 years). Patients in the STI group stopped therapy for a total of
      241 STI cycles, their mean off-therapy period was 65.3% of the follow-up. The
      primary end point occurred in 12.1% of patients on STI and in 11.6% of controls
      [odds ratio 1.05; 95% confidence interval 0.54-2.05]. A higher proportion of
      patients in the STI arm were diagnosed with pneumonia (P = 0.037), whereas
      clinical events influencing the cardiovascular risk of patients were
      significantly (P < 0.0001) more frequent among controls. Eight patients (4.8%) in
      the STI group and 11 (6.7%) controls developed viral resistance [odds ratio 0.79,
      95% confidence interval 0.27-1.81]. The mean daily therapeutic cost was 20.29
      euro for controls and dropped to 9.07 euro in the STI arm (P < 0.0001).
      CONCLUSION: The two strategies may be considered clinically equivalent. CD4 cell
      guided STIs seem a possible alternative for chronically infected individuals
      responding to HAART provided that CD4 cell decrements would be steadily
      maintained above a safe threshold.

PMID- 19114871
TI  - Nebivolol Might Be Beneficial in the Prevention and Treatment of Diabetic
      Neuropathy.

PMID- 19114870
TI  - Changing mortality risk associated with CD4 cell response to antiretroviral
      therapy in South Africa.
AB  - OBJECTIVE: To determine the relationship between mortality risk and the CD4 cell
      response to antiretroviral therapy (ART). DESIGN: Observational community-based
      ART cohort in South Africa. METHODS: CD4 cell counts were measured 4 monthly, and
      deaths were prospectively ascertained. Cumulative person-time accrued within a
      range of updated CD4 cell count strata (CD4 cell-strata) was calculated and used
      to derive CD4 cell-stratified mortality rates. RESULTS: Patients (2423) (median
      baseline CD4 cell count of 105 cells/microl) were observed for up to 5 years of
      ART. One hundred and ninety-seven patients died during 3155 person-years of
      observation. In microltivariate analysis, mortality rate ratios associated with 0
      49, 50-99, 100-199, 200-299, 300-399, 400-499 and at least 500 cells/microl
      updated CD4 cell-strata were 11.6, 4.9, 2.6, 1.7, 1.5, 1.4 and 1.0, respectively.
      Analysis of CD4 cell count recovery permitted calculations of person-time accrued
      within these CD4 cell-strata. Despite rapid immune recovery, high mortality in
      the first year of ART was related to the large proportion of person-time accrued
      within CD4 cell-strata less than 200 cells/microl. Moreover, patients with
      baseline CD4 cell counts less than 100 cells/microl had much higher cumulative
      mortality estimates at 1 and 4 years (11.6 and 16.7%) compared with those of
      patients with baseline counts of at least 100 cells/microl (5.2 and 9.5%) largely
      because of greater cumulative person-time at CD4 cell counts less than 200
      cells/microl. CONCLUSION: Updated CD4 cell counts are the variable most strongly
      associated with mortality risk during ART. High cumicrolative mortality risk is
      associated with person-time accrued at low CD4 cell counts. National HIV
      programmes in resource-limited settings should be designed to minimize the time
      patients spend with CD4 cell counts less than 200 cells/microl both before and
      during ART.

PMID- 19114872
TI  - Does synchronizing initiation of therapy affect adherence to concomitant use of
      antihypertensive and lipid-lowering therapy?
AB  - Although efficacious medications are available to treat hypertension and
      dyslipidemia, treatment adherence is often poor. This retrospective study
      evaluated adherence in patients newly initiating antihypertensive (AH) and lipid
      lowering (LL) therapies simultaneously versus within 180 days of one another.
      Data were analyzed for US managed care plan enrollees initiating AH before LL
      (cohort 1;n = 7099), LL before AH (cohort 2; n = 3229), or AH/LL simultaneously
      (cohort 3; n = 5072). A multivariate model evaluated potential predictors of
      adherence (medication possession ratio >or= 0.80 over a bimonthly period).
      Percentages of patients adherent to AH/LL at 2, 6, and 12 months were as follows:
      59.4%, 32.7%, and 31.3% in cohort 1; 45.0%, 30.8%, and 31.0% in cohort 2; and
      75.2%, 34.4%, and 34.0% in cohort 3, respectively. After adjustment for potential
      confounders, patients initiating AH before LL therapy, or LL before AH therapy,
      were less likely to be adherent than patients prescribed both agents
      simultaneously (odds ratios = 0.838 and 0.691, respectively; P , 0.0001).
      Synchronous initiation of AH and LL therapies is an important predictor of
      adherence.

PMID- 19114873
TI  - Updates on cytochrome P450-mediated cardiovascular drug interactions.
AB  - Cytochrome P (CYP) 450 is a superfamily of hemoproteins that play an important
      role in the metabolism of steroid hormones, fatty acids, and many medications.
      Many agents used for management of cardiovascular diseases are substrates,
      inhibitors, or inducers of CYP450 enzymes.When two agents that are substrates,
      inhibitors, or inducers of CYP450 are administered together, drug interactions
      with significant clinical consequences may occur. This review discusses CYP450
      mediated cardiovascular drug interactions as well as noncardiovascular drug
      interactions that produced significant cardiovascular side effects. The
      principles in predicting drug interactions are also discussed.

PMID- 19114874
TI  - Cardiovascular manifestations of insulin resistance.
AB  - Data from the Centers for Disease Control and Prevention indicate that the
      prevalence of diabetes is increasing steadily and is coupled with a rise in
      obesity. Studies such as the Nurses' Health Study show that even slight glucose
      abnormalities, namely insulin resistance, increase the risk of myocardial
      infarctions, strokes, other cardiovascular disease, and mortality. Insulin
      resistance was found to accelerate atherosclerosis, inflammation, the onset of
      diabetes, cardiovascular disease, obesity, hypertension, chronic kidney disease,
      and dyslipidemia. Adiponectin was found to have potent antiinflammatory and
      antiatherosclerotic effects. Similarly, studies indicate that peroxisome
      proliferators-activated receptor agonists have the potential to treat obesity,
      diabetes, and atherosclerosis. From a preventive standpoint, it was shown that
      intensive glucose control reduces long-term cardiovascular risk. This intensive
      control approach included the use of thiazolidinediones (TZDs; troglitazone,
      pioglitazone, and rosiglitazone), which were demonstrated to have vascular and
      nonglycemic effects beyond glucose-lowering. A drawback of using TZDs is
      peripheral fluid retention. The DREAM study showed that participants with
      impaired fasting glucose or impaired glucose tolerance who are free from
      cardiovascular disease benefited significantly from taking 8 mg rosiglitazone per
      day. The ADOPT study provided evidence that rosiglitazone is more efficient at
      controlling glycemic loss and maintaining low glycosylated hemoglobin levels than
      metformin and glyburide. Data from the CHICAGO study indicate that the
      progression of carotid artery intima-media thickness, a marker of atherosclerosis
      and a surrogate end point for cardiovascular disease, was slowed more with
      pioglitazone than glimepiride in a racially diverse population of men and women
      with diabetes mellitus type 2. Overall, investigators have shifted from a focus
      on hyperglycemia to a multifactorial approach to risk management in diabetes.
      This multifactorial approach includes intensive glycemic control, lifestyle
      intervention, and intensive management of comorbid (dyslipidemia, hypertension,
      early renal disease) conditions. The implementation of a regular, rigorous
      exercise and diet program greatly decreased insulin resistance and allowed far
      more patients to reach their glycosylated hemoglobin goals. Studies with
      atrovastatin show significant improvement in cardiovascular risk factors in
      patients with diabetes and hypertension. Short-term studies provide support for
      the administration of a combination of TZD + sulfonylureas in patients with
      diabetes mellitus type 2. Likewise, studies have shown that a combination of TZDs
      + metformin reduced the risk of myocardial infarction. Finally, dipeptidyl
      peptidase-IV inhibitors and glycolipoprotein-1 analogs show potential for helping
      prevent the deterioration of glucose metabolism in early diabetes mellitus type
      2.

PMID- 19114875
TI  - Bupropion-associated QRS prolongation unresponsive to sodium bicarbonate therapy.
AB  - We describe a case of bupropion-associated QRS prolongation that was unresponsive
      to intravenous bolus therapy of sodium bicarbonate. Bupropion may cause seizures
      and conduction delays similar to tricyclic antidepressants in the overdose
      setting by an unknown mechanism.

PMID- 19114876
TI  - Incidence of new stroke or new myocardial infarction or death at 39-month follow
      up in patients with diabetes mellitus, hypertension, or both treated with and
      without angiotensin-converting enzyme inhibitors or angiotensin receptor
      blockers.
AB  - We investigated in 306 patients, mean age 57 +/- 10 years, with diabetes mellitus
      (202 patients) or hypertension (179 patients), whether treatment with angiotensin
      converting enzyme inhibitors or angiotensin receptor blockers (ARBs) reduced the
      incidence of new stroke or new myocardial infarction (MI) or death. At 39-month
      follow up, new stroke or new MI or death developed in 49 of 228 patients (21%)
      treated with ACE inhibitors or ARBs and in 33 of 78 patients (42%) treated
      without angiotensin-converting enzyme inhibitors or ARBs (P = 0.0001). Stepwise
      Cox regression analysis showed that significant independent predictors of the
      time to development of new stroke or new MI or death were 1) use of angiotensin
      converting enzyme inhibitors or ARBs (risk ratio, 0.21), 2) diabetes (risk ratio,
      4.01), 3) left ventricular hypertrophy (risk ratio, 6.71), 4) prior stroke (risk
      ratio, 4.00), and 5) prior MI (risk ratio, 3.69).

PMID- 19114877
TI  - Atherothrombosis and the management of the vulnerable vascular patient.
AB  - Atherothrombosis is a generalized and diffuse progressive process manifesting in
      multiple vascular beds leading to acute coronary syndrome (ACS), ischemic stroke,
      and peripheral arterial disease. The American Heart Association estimates the
      prevalence of ischemic stroke, coronary heart disease, and peripheral artery
      disease to be 4.8, 13.2, and 8 million, respectively. According to the World
      Health Organization, in 2004, atherothrombosis was the leading cause of death
      worldwide. Twenty-two percent of all deaths are attributed to atherothrombosis,
      which is greater than the percentage of deaths from AIDS and cancer combined.
      Data from the Framingham Heart Study has shown atherothrombosis significantly
      reduces life expectancy. According to current data, there is an established
      relationship among coronary artery disease, peripheral vascular disease, and
      cardiovascular disease. The REACH registry demonstrated that the 1-year
      cardiovascular event rates increase with the number of symptomatic disease
      locations. Unstable angina/non-ST-segment elevation MI is a major public health
      problem and represents the most common reason for hospital admission for coronary
      heart disease. Classification of "vulnerable patients" will help identify those
      with a high probability of developing cardiac events in the near future, and
      their early detection and treatment would help 50 to 60 million Americans over
      the age of 35. The management of patients with ischemic coronary disease consists
      of 2 approaches: revascularization and systemic (aspirin, clopidogrel, lipid
      lowering therapy, angiotensin-converting enzyme inhibitors, and beta-blockers).
      There is a substantial long-term cardiovascular risk after discharge with non-ST
      elevation acute coronary syndrome with an annual mortality rate estimated at 6%.
      This emphasizes the importance of risk stratification and aggressive management
      strategies that target high-risk patients. Based on CAPRIE study and Cure trial
      results, patients can benefit from clopidogrel or its combination with aspirin.
      CRUSADE registry data reveal some acute medications are still being underused,
      most notably GP IIb/IIIa inhibitors (47%) and clopidogrel (54%). Improved
      American College of Cardiology/American Heart Association guideline adherence is
      directly associated with reduced in-hospital mortality, and thus the need for
      quality improvement is imperative.

PMID- 19114878
TI  - Novel and conventional serum biomarkers predicting acute kidney injury in adult
      cardiac surgery--a prospective cohort study.
AB  - OBJECTIVE: To compare the value of novel with conventional serum biomarkers in
      the prediction of acute kidney injury (AKI) in adult cardiac surgical patients
      according to preoperative renal function. DESIGN: Single-center, prospective
      observational study. SETTING: Tertiary hospital. PATIENTS: One hundred adult
      cardiac surgical patients. MEASUREMENTS AND MAIN RESULTS: We measured
      concentrations of plasma neutrophil gelatinase-associated lipocalin (NGAL), and
      serum cystatin C, and creatinine and urea at baseline, on arrival in the
      intensive care unit (ICU) and at 24 hours postoperatively. We assessed such
      biomarkers in relation to the development of AKI (>50% increase in creatinine
      from baseline) and to a composite end point (need for renal replacement therapy
      and in-hospital mortality). We defined an area under the receiver operating
      characteristic curve of 0.60-0.69 as poor, 0.70-0.79 as fair, 0.80-0.89 as good,
      and 0.90-1.00 as excellent in terms of predictive value. On arrival in ICU,
      plasma NGAL and serum cystatin C were of good predictive value, but creatinine
      and urea were of poor predictive value. After exclusion of patients with
      preoperative renal impairment (estimated glomerular filtration rate <60 mL/min),
      the predictive performance for AKI of all renal biomarkers on arrival in ICU
      remained unchanged except for cystatin C, which was of fair value in such
      patients. At 24 hours postoperatively, all renal biomarkers were of good
      predictive value. On arrival in ICU, novel biomarkers were superior to
      conventional biomarkers (p < 0.05). Plasma NGAL (p = 0.015) and serum cystatin C
      (p = 0.007) were independent predictors of AKI and of excellent value in the
      prediction of the composite end point. CONCLUSIONS: Early postoperative
      measurement of plasma NGAL was of good value in identifying patients who
      developed AKI after adult cardiac surgery. Plasma NGAL and serum cystatin C were
      superior to conventional biomarkers in the prediction of AKI and were also of
      prognostic value in this setting.

PMID- 19114879
TI  - Activation of coagulation and inhibition of fibrinolysis in the human lung on
      bronchial instillation of lipoteichoic acid and lipopolysaccharide.
AB  - OBJECTIVE: Pneumonia is characterized by an acute inflammatory response in the
      lung, which is frequently associated with changes in coagulation and fibrinolysis
      in the bronchoalveolar space. Here, we compared the effects of lipoteichoic acid
      (LTA), a major cell wall component of Gram-positive bacteria, and
      lipopolysaccharide (LPS), in the human bronchoalveolar space. DESIGN: Controlled
      in vivo volunteer study. SETTING: Clinical research unit. SUBJECTS: Twenty-three
      healthy nonsmoking male volunteers. INTERVENTIONS: Sterile saline was instilled
      into a lung subsegment followed by bronchoscopic instillation of either LTA
      (Staphylococcus aureus, at a dose of 4, 20, or 100 ng/kg body weight) or LPS
      (Escherichia coli, 4 ng/kg body weight) into the contralateral lung.
      Bronchoalveolar lavage fluid was obtained 6 hours thereafter. MEASUREMENTS AND
      MAIN RESULTS: Bronchial instillation of LTA- or LPS-activated bronchoalveolar
      coagulation, as reflected by increases in the levels of thrombin-antithrombin
      complexes, d-dimer, and soluble tissue factor. Concurrently, LTA and LPS
      inhibited anticoagulant mechanisms, as indicated by reductions in antithrombin,
      Protein C, and Activated Protein C concentrations together with elevated levels
      of soluble thrombomodulin. Both LTA and LPS administration was associated with an
      inhibition of pulmonary fibrinolysis, as measured by a reduction in plasminogen
      activator activity and elevated levels of plasminogen activator inhibitor type I.
      CONCLUSIONS: This study is the first to describe the effects of LTA on hemostasis
      in humans, demonstrating that LTA induces similar changes in the human
      bronchoalveolar space as LPS, characterized by activation of coagulation with
      concurrent inhibition of anticoagulant and fibrinolytic pathways.

PMID- 19114881
TI  - Systemic use of the endolysin Cpl-1 rescues mice with fatal pneumococcal
      pneumonia.
AB  - OBJECTIVES: Community-acquired pneumonia is a very common infectious disease
      associated with significant morbidity and mortality. Streptococcus pneumoniae is
      the predominant pathogen in this disease, and pneumococcal resistance to multiple
      antibiotics is increasing. The recently purified bacteriophage endolysin Cpl-1
      rapidly and specifically kills pneumococci on contact. The aim of this study was
      to determine the therapeutic potential of Cpl-1 in a mouse model of severe
      pneumococcal pneumonia. DESIGN: Controlled, in vivo laboratory study. SUBJECTS:
      Female C57/Bl6 mice, 8-12 weeks old. INTERVENTIONS: Mice were transnasally
      infected with pneumococci and therapeutically treated with Cpl-1 or amoxicillin
      by intraperitoneal injections starting 24 or 48 hours after infection.
      MEASUREMENTS AND MAIN RESULTS: Judged from clinical appearance, decreased body
      weight, reduced dynamic lung compliance and Pao2/Fio2 ratio, and morphologic
      changes in the lungs, mice suffered from severe pneumonia at the onset of
      therapy. When treatment was commenced 24 hours after infection, 100% Cpl-1
      treated and 86% amoxicillin-treated mice survived otherwise fatal pneumonia and
      showed rapid recovery. When treatment was started 48 hours after infection, mice
      had developed bacteremia, and three of seven (42%) Cpl-1-treated and five of
      seven (71%) amoxicillin-treated animals survived. Cpl-1 dramatically reduced
      pulmonary bacterial counts, and prevented bacteremia, systemic hypotension, and
      lactate increase when treatment commenced at 24 hours. In vivo, treatment with
      Cpl-1 or amoxicillin effectively reduced counts of penicillin-susceptible
      pneumococci. The inflammatory response in Cpl-1-and amoxicillin-treated mice was
      lower than in untreated mice, as determined by multiplex cytokine assay of lung
      and blood samples. In human epithelial cell cultures, lysed bacteria evoked less
      proinflammatory cytokine release and cell death, as compared with viable
      bacteria. CONCLUSIONS: Cpl-1 may provide a new therapeutic option in the
      treatment of pneumococcal pneumonia.

PMID- 19114882
TI  - Unexplained hypotension: the spectrum of dynamic left ventricular outflow tract
      obstruction in critical care settings.
AB  - OBJECTIVE: To illustrate the clinical and hemodynamic abnormalities caused by
      dynamic left ventricular outflow tract obstruction (LVOTO) in critical care
      setting. DESIGN: We reviewed cases referred to Cardiology with echocardiographic
      evidence of LVOTO and their clinical presentations. We present those cases where
      LVOTO can transiently occur without hypertrophic cardiomyopathy when inotropic
      agents are used for hypotension. MEASUREMENTS AND MAIN RESULTS: Five women in the
      50-70 age range and prior history of hypertension presented with various symptoms
      like chest discomfort, fatigue, dizziness, atrial fibrillation, and hypotension.
      An ejection systolic murmur was noted most often in the left third intercostal
      space and ECG revealed ST-T wave abnormalities. LVOTO caused by mitral systolic
      anterior motion was detected by echocardiography and catheterization excluded
      acute coronary disease. In critical care setting, LVOTO can occur due to apical
      ballooning syndrome, coronary disease, medications, volume depletion, and
      valvular abnormalities. Because this condition mimics acute coronary syndrome or
      other etiologies of hypotension in medical and surgical intensive care units,
      appropriate treatment can be delayed. Nonhypertrophic cardiomyopathy LVOTO
      usually responds well to fluid replacement, beta blockers, and medication
      changes. CONCLUSIONS: LVOTO should be suspected especially in women presenting
      with hypotension and systolic murmur in critical care settings. Clinical acumen
      and timely echocardiography are required to effectively counter this transient
      but potentially lethal problem.

PMID- 19114880
TI  - Management of aneurysmal subarachnoid hemorrhage.
AB  - OBJECTIVE: Acute aneurysmal subarachnoid hemorrhage (SAH) is a complex
      multifaceted disorder that plays out over days to weeks. Many patients with SAH
      are seriously ill and require a prolonged intensive care unit stay.
      Cardiopulmonary complications are common. The management of patients with SAH
      focuses on the anticipation, prevention, and management of these secondary
      complications. DATA SOURCES: Source data were obtained from a PubMed search of
      the medical literature. DATA SYNTHESIS AND CONCLUSION: The rupture of an
      intracranial aneurysm is a sudden devastating event with immediate neurologic and
      cardiac consequences that require stabilization to allow for early diagnostic
      angiography. Early complications include rebleeding, hydrocephalus, and seizures.
      Early repair of the aneurysm (within 1-3 days) should take place by surgical or
      endovascular means. During the first 1-2 weeks after hemorrhage, patients are at
      risk of delayed ischemic deficits due to vasospasm, autoregulatory failure, and
      intravascular volume contraction. Delayed ischemia is treated with combinations
      of volume expansion, induced hypertension, augmentation of cardiac output,
      angioplasty, and intra-arterial vasodilators. SAH is a complex disease with a
      prolonged course that can be particularly challenging and rewarding to the
      intensivist.

PMID- 19114883
TI  - Increased splanchnic oxygen extraction because of routine nursing procedures.
AB  - OBJECTIVE: Multiple organ failure is a common complication of acute circulatory
      and respiratory failure. We hypothesized that therapeutic interventions used
      routinely in intensive care can interfere with the perfusion of the gut and the
      liver, and thereby increase the risk of mismatch between oxygen supply and
      demand. DESIGN: Prospective, observational study. SETTING: Interdisciplinary
      intensive care unit (ICU) of a university hospital. PATIENTS: Thirty-six patients
      on mechanical ventilation with acute respiratory or circulatory failure or severe
      infection were included. INTERVENTIONS: Insertion of a hepatic venous catheter.
      MEASUREMENTS AND MAIN RESULTS: Daily nursing procedures were recorded. A decrease
      of >or=5% in hepatic venous oxygen saturation (Sho2) was considered relevant.
      Observation time was 64 (29-104) hours (median [interquartile range]). The ICU
      stay was 11 (8-15) days, and hospital mortality was 35%. The number of periods
      with procedures/patient was 170 (98-268), the number of procedure-related
      decreases in Sho2 was 29 (13-41), and the number of decreases in Sho2 unrelated
      to procedures was 9 (4-19). Accordingly, procedure-related Sho2 decreases
      occurred 11 (7-17) times per day. Median Sho2 decrease during the procedures was
      7 (5-10)%, and median increase in the gradient between mixed and hepatic venous
      oxygen saturation was 6 (4-9)%. Procedures that caused most Sho2 decreases were
      airway suctioning, assessment of level of sedation, and changing patients'
      position. Sho2 decreases were associated with small but significant increases in
      heart rate and intravascular pressures. Maximal Sequential Organ Failure
      Assessment scores in the ICU correlated with the number of Sho2 decreases (r:
      .56; p < 0.001) and with the number of procedure-related Sho2 decreases (r: .60;
      p < 0.001). CONCLUSIONS: Patients are exposed to repeated episodes of impaired
      splanchnic perfusion during routine nursing procedures. More research is needed
      to examine the correlation, if any, between nursing procedures and hepatic venous
      desaturation.

PMID- 19114884
TI  - The clinical effectiveness of central venous catheters treated with anti
      infective agents in preventing catheter-related bloodstream infections: a
      systematic review.
AB  - OBJECTIVES: To assess the clinical effectiveness of central venous catheters
      (CVCs) treated with anti-infective agents (AI-CVCs) in preventing catheter
      related bloodstream infections (CRBSI). DATA SOURCES: MEDLINE (OVID), EMBASE,
      SCI//Web of Science, SCI/ISI Proceedings, and the Cochrane Library. STUDY
      SELECTION: A systematic review of the literature was conducted using
      internationally recognized methodology. All included articles were reports of
      randomized controlled trials comparing the clinical effectiveness of CVCs treated
      with AI-CVCs with either standard CVCs or another anti-infective treated
      catheter. Articles requiring in-house preparation of catheters or that only
      reported interim data were excluded. DATA EXTRACTION: Data extraction was carried
      out independently and crosschecked by two reviewers using a pretested data
      extraction form. DATA SYNTHESIS: Meta-analyses were conducted to assess the
      effectiveness of AI-CVCs in preventing CRBSI, compared with standard CVCs.
      Results are presented in forest plots with 95% confidence intervals. RESULTS:
      Thirty-eight randomized controlled trials met the inclusion criteria.
      Methodologic quality was generally poor. Meta-analyses of data from 27 trials
      assessing CRBSI showed a strong treatment effect in favor of AI-CVCs (odds ratio
      0.49 (95% confidence interval 0.37-0.64) fixed effects, test for heterogeneity,
      chi-square = 28.78, df = 26, p = 0.321, I = 9.7). Results subgrouped by the
      different types of anti-infective treatments generally demonstrated treatment
      effects favoring the treated catheters. Sensitivity analyses investigating the
      effects of methodologic differences showed no differences to the overall
      conclusions of the primary analysis. CONCLUSION: AI-CVCs appear to be effective
      in reducing CRBSI compared with standard CVCs. However, it is important to
      establish whether this effect remains in settings where infection-prevention
      bundles of care are established as routine practice. This review does not address
      this question and further research is required.

PMID- 19114885
TI  - Influence of vasopressor agent in septic shock mortality. Results from the
      Portuguese Community-Acquired Sepsis Study (SACiUCI study).
AB  - OBJECTIVE: Guidelines for the adrenergic support of septic shock are
      controversial. In patients with community-acquired septic shock, we assessed the
      impact of the choice of vasopressor support on mortality. DESIGN: Cohort,
      multiple center, observational study. SETTING: Seventeen Portuguese intensive
      care units (ICUs). PATIENTS: All adult patients admitted to a participating ICU
      between December 2004 and November 2005. INTERVENTIONS: None. MEASUREMENTS AND
      MAIN RESULTS: Patients were followed up during the first five ICU days, the day
      of discharge or death, and hospital outcome. Eight hundred ninety-seven
      consecutive patients with community-acquired sepsis (median age, 63 years; 577
      men; and hospital mortality, 38%) were studied. Of the 458 patients with septic
      shock, 73% received norepinephrine and 50.5% dopamine. The norepinephrine group
      had a higher hospital mortality (52% vs. 38.5%, p = 0.002). A Kaplan-Meier
      survival curve showed diminished 28-day survival in the norepinephrine group (log
      rank = 22.6, p < 0.001). A Cox proportional hazard analysis revealed that the
      administration of norepinephrine was associated with an increased risk of death
      (adjusted hazard ratio, 2.501; 95% confidence interval, 1.413-4.425; p = 0.002).
      In a multivariate analysis with ICU mortality as the dependent factor, Simplified
      Acute Physiology Score II and norepinephrine administration were independent risk
      factors for ICU mortality in patients with septic shock. CONCLUSIONS: In patients
      with community-acquired septic shock, our data suggest that norepinephrine
      administration could be associated with worse outcome.

PMID- 19114886
TI  - Dynamic preload indicators fail to predict fluid responsiveness in open-chest
      conditions.
AB  - OBJECTIVE: Dynamic preload indicators like pulse pressure variation (PPV) and
      stroke volume variation (SVV) are increasingly being used for optimizing cardiac
      preload since they have been demonstrated to predict fluid responsiveness in a
      variety of perioperative settings. However, in open-chest conditions, the value
      of these indices has not been systematically examined yet. We, therefore,
      evaluated the ability of PPV and SVV to predict fluid responsiveness under open-
      and closed-chest conditions. DESIGN: Prospective, controlled, clinical study.
      SETTING: University hospital. PATIENTS: Twenty-two patients scheduled for
      elective coronary artery bypass graft surgery. INTERVENTIONS: Defined volume
      loads (VL) (10 mL kg-1 hydroxyethyl starch 6%) intra- and postoperatively.
      MEASUREMENTS AND MAIN RESULTS: Stroke volume index was measured 1) before and
      after a VL intraoperatively in open-chest conditions, and 2) under closed-chest
      conditions within 1 hour after arrival in the intensive care unit. Central venous
      pressure and global end diastolic volume were assessed as static preload
      indicators. In addition, PPV and SVV (both obtained with PiCCO system) were
      recorded. Fluid-responders were defined by an increase in stroke volume index
      >or=12% subsequent to the VL. Receiver operating characteristic analysis showed
      that all preload indicators failed to predict fluid responsiveness in open-chest
      conditions. Under closed-chest conditions, the areas under the receiver operating
      characteristic curve for PPV and SVV were 0.884 (p = 0.004) and 0.911 (p =
      0.003), respectively, whereas the static and volumetric preload parameters failed
      to predict fluid responsiveness. A PPV of >or=10% identified fluid-responders
      with a sensitivity of 64% and a specificity of 100%, while a SVV of >8%
      identified fluid-responders with a sensitivity of 100% and a specificity of 78%.
      CONCLUSIONS: Our results suggest that the dynamic preload indicators PPV and SVV
      are able to predict fluid responsiveness under closed-chest conditions, whereas
      all static and dynamic preload indicators fail to predict fluid responsiveness
      under open-chest conditions.

PMID- 19114887
TI  - Perioperative volume replacement in children undergoing cardiac surgery: albumin
      versus hydroxyethyl starch 130/0.4.
AB  - OBJECTIVE: To compare 4% albumin with 6% hydroxyethyl starch (HES) 130/0.4 in
      terms of perioperative blood loss and intraoperative fluid requirements in
      children undergoing cardiac surgery. DESIGN: Prospective randomized study.
      SETTING: Single University Hospital. PATIENTS: Pediatric patients undergoing
      cardiac surgery with cardiopulmonary bypass. INTERVENTIONS: One hundred nineteen
      children were randomized to receive up to 50 mL.kg of either 4% albumin (Alb: n =
      59) or 6% HES 130/0.4 (HES: n = 60) for intraoperative fluid volume replacement
      including the cardiopulmonary bypass priming fluid. Ringer's lactate was used for
      further intraoperative volume needs. Monitoring, anesthetic, and surgical
      techniques were standardized. Packed red blood cells were administered according
      to a strict transfusion protocol. Intra- and postoperative blood loss were
      measured and also calculated from children's estimated blood volume, pre- and
      postoperative hematocrit, and volume of transfused packed red blood cells.
      MEASUREMENTS AND MAIN RESULTS: Volume of colloid used intraoperatively was
      similar in both groups (median [interquartiles]) (Alb: 50 [45-50] mL x kg; HES:
      50 [37-50] mL x kg). Measured and calculated blood loss were not different
      between groups, but a higher number of children in the albumin group required
      allogeneic blood transfusion (78% vs. 57%; difference between proportions: 0.213;
      95% confidence interval: 0.05-0.38; p = 0.0188). Intraoperative fluid balance was
      lower in the HES group (Alb 23 [11-39] mL x kg; HES: 12 [-5-30] mL x kg; p =
      0.005). Postoperative outcome was not different between groups. CONCLUSIONS: In
      children undergoing cardiac surgery, 6% HES 130/0.4 may represent an interesting
      alternative to 4% albumin for intraoperative fluid volume replacement because of
      its lower cost.

PMID- 19114888
TI  - Increasing plasma glutamine in postoperative patients fed an arginine-rich immune
      enhancing diet--a pharmacokinetic randomized controlled study.
AB  - OBJECTIVE: Immune-enhancing diets (IEDs) rich in arginine (ARG) reduce morbi
      mortality in trauma and surgical patients. Among the pharmaconutrients inducing
      these effects, ARG may be involved by generating active metabolites such as
      glutamine (GLN). However, the ability of an ARG-enriched diet to normalize GLN
      plasma levels in intensive care unit (ICU) patients has never been documented. To
      analyze plasma GLN and related amino acid (AA) kinetics in response to an ARG
      enriched IED in ICU surgical patients. DESIGN: This prospective, randomized,
      single-blind, comparative study was performed on 22 patients randomized to
      receive total enteral nutrition for 7 days with either an ARG-enriched IED or a
      standard formula (rendered isonitrogenous to the IED, S group, n = 11), providing
      30 kcal/kg/day and 0.3 g N/kg/day. MEASUREMENTS: Plasma AA concentrations were
      measured on day 5 after a 3-hour washout period (basal values = T0) and after 30,
      60, 90, 120, 180, and 360 minutes of enteral nutrition. The primary end point was
      the variation in plasma GLN from T0 to T90. RESULTS: Only the IED-fed patients
      showed an increase in plasma levels of GLN (differences [T90 - T0]: +40 +/- 6 vs.
      -35 +/- 18 micromol/L, mean +/- sem, p < 0.05, two-way analysis of variance), ARG
      (+35 +/- 5 vs.+1 +/- 4 micromol/L, p < 0.05), ornithine (+23 +/- 6 vs. -2 +/- 2
      micromol/L, p < 0.05), and proline (+36 +/- 10 vs. -6 +/- 11 micromol/L, p <
      0.05). CONCLUSION: To our knowledge, this is the first reported pharmacokinetic
      study on an IED even though these products have been on the market for 20 years.
      Our main result is that administering an ARG-enriched IED causes a significant
      increase in plasma GLN probably from de novo GLN synthesis from ARG. This
      suggests that the ARG present in IED can serve to supply GLN to ICU patients, who
      are usually depleted in this conditionally essential AA during injury.

PMID- 19114889
TI  - Principles of electrical impedance tomography and its clinical application.
AB  - OBJECTIVE: This review outlines the basic principle, in addition to validated and
      upcoming clinical use of electrical impedance tomography (EIT). EIT generates
      functional tomograms of the thorax for detection of changes in regional lung
      aeration. These images allow an intraindividual comparison of changes in regional
      lung function. Specifically, EIT aims to optimize ventilation therapy in patients
      with acute lung failure. DATA SOURCES: PubMed: National Library of Medicine and
      the National Institutes of Health. STUDY SELECTION: Studies with the key words
      "electrical impedance tomography" since 1983. DATA EXTRACTION: Qualitative and
      quantitative results of the studies. DATA SYNTHESIS: We summarize basic
      principles of the technique and subsequent analyzing methods, and give an
      overview of clinical and scientific questions that can be addressed by EIT.
      CONCLUSION: Potential applications in the future as well as limitations of EIT
      technology are described. In summary, EIT is a promising functional tomography
      technology on the verge of its clinical application.

PMID- 19114890
TI  - Effects of an angiotensin-converting enzyme inhibitor on the inflammatory
      response in in vivo and in vitro models.
AB  - OBJECTIVE: Sepsis remains a major health threat in intensive care medicine. The
      renin-angiotensin system (ACE) affects inflammatory responses. In addition,
      angiotensin-converting enzyme inhibitors act to ameliorate lung injury. To
      investigate whether the widely used ACE inhibitor enalapril, used to treat
      hypertension, could inhibit secretion of cytokines and high-mobility group box 1
      (HMGB1) protein, thus reducing lung damage in a rat model of lipopolysaccharide
      (LPS)-induced sepsis. DESIGN: Randomized, prospective animal study. SETTING:
      University medical center research laboratory. SUBJECTS: Male Wistar rats.
      INTERVENTIONS: LPS was administered intravenously to rats, with or without
      intraperitoneal pretreatment with enalapril. In addition, mouse macrophage
      RAW264.7 cells were stimulated with LPS, with and without simultaneous enalapril
      treatment. MEASUREMENTS AND MAIN RESULTS: Histologic examination showed marked
      reduction of interstitial congestion, edema, inflammation, and hemorrhage in lung
      tissue harvested 12 hours after treatment with both agents compared with LPS
      administration alone. Plasma concentration of angiotensin II was strongly induced
      by LPS; this induction was inhibited by the enalapril pretreatment. Likewise, LPS
      induced secretion of proinflammatory cytokines and HMGB1 protein was inhibited by
      enalapril. The presence of HMGB1 protein in the lung was examined directly by
      immunohistochemistry; the number of stained cells was significantly lower in LPS
      treated animals that also received enalapril. In the in vitro studies, enalapril
      administration inhibited the phosphorylation of IkappaB. CONCLUSIONS: The ACE
      inhibitor enalapril blocked the LPS-induced inflammatory response and protected
      against the acute lung injury normally associated with endotoxemia in this rat
      sepsis model. Given these results, enalapril is a strong candidate as a
      therapeutic agent for sepsis.

PMID- 19114892
TI  - Phosphodiesterase 2 inhibition diminished acute lung injury in murine
      pneumococcal pneumonia.
AB  - OBJECTIVE: Severe pneumococcal pneumonia frequently causes respiratory failure.
      Both pathogen factors and an uncontrolled host response may contribute to acute
      lung injury by impairing microvascular barrier function. Phosphodiesterase 2
      (PDE2) was examined as a potential target in pneumonia-induced lung microvascular
      hyperpermeability. DESIGN: Controlled, in vitro, ex vivo, and in vivo laboratory
      study. SUBJECTS: Female Balb/C and C57Bl/6 mice, 8-12 weeks old. INTERVENTIONS:
      Human umbilical vein endothelial cells and isolated mouse lungs were challenged
      with the pneumococcal exotoxin pneumolysin in the presence or absence of the
      selective PDE2 inhibitors 9-(6-phenyl-2-oxohex-3-yl)-2-(3,4-dimethoxybenzyl)
      purin-6one (PDP) or hydroxy-PDP. Transcellular electrical resistance or human
      serum albumin leakage in bronchoalveolar lavage fluid was determined,
      respectively. In addition, we induced pneumococcal pneumonia in mice and treated
      with hydroxy-PDP via continuous subcutaneous application by osmotic pumps. Human
      serum albumin leakage in bronchoalveolar lavage fluid was measured 48 hours after
      transnasal infection, and lung specimens were analyzed by TaqMan real-time
      polymerase chain reaction and Western blot for PDE2 gene and protein expression.
      MEASUREMENTS AND MAIN RESULTS: In isolated perfused mouse lungs and in human
      umbilical vein endothelial cell monolayers, selective inhibition of PDE2 markedly
      decreased pneumolysin-induced hyperpermeability. Furthermore, in murine
      pneumococcal pneumonia, pulmonary PDE2-mRNA and -protein expression was
      significantly increased, and pneumonia-induced vascular permeability was
      distinctively reduced by PDE2 inhibition. CONCLUSIONS: PDE2 inhibition diminished
      microvascular leakage in pneumococcal pneumonia, and pulmonary PDE2 upregulation
      may play a crucial role in this respect. Selective PDE2 inhibitors thus may offer
      a promising therapeutic approach in severe pneumococcal pneumonia.

PMID- 19114891
TI  - N-acetylcysteine as adjunctive treatment in severe malaria: a randomized, double
      blinded placebo-controlled clinical trial.
AB  - OBJECTIVE: Markers of oxidative stress are reported to be increased in severe
      malaria. It has been suggested that the antioxidant N-acetylcysteine (NAC) may be
      beneficial in treatment. We studied the efficacy and safety of parenteral NAC as
      an adjunct to artesunate treatment of severe falciparum malaria. DESIGN: A
      randomized, double-blind, placebo-controlled trial on the use of high-dose
      intravenous NAC as adjunctive treatment to artesunate. SETTING: A provincial
      hospital in Western Thailand and a tertiary referral hospital in Chittagong,
      Bangladesh. PATIENTS: One hundred eight adult patients with severe falciparum
      malaria. INTERVENTIONS: Patients were randomized to receive NAC or placebo as an
      adjunctive treatment to intravenous artesunate. MEASUREMENTS AND MAIN RESULTS: A
      total of 56 patients were treated with NAC and 52 received placebo. NAC had no
      significant effect on mortality, lactate clearance times (p = 0.74), or coma
      recovery times (p = 0.46). Parasite clearance time was increased from 30 hours
      (range, 6-144 hours) to 36 hours (range, 6-120 hours) (p = 0.03), but this could
      be explained by differences in admission parasitemia. Urinary F2-isoprostane
      metabolites, measured as a marker of oxidative stress, were increased in severe
      malaria compared with patients with uncomplicated malaria and healthy volunteers.
      Admission red cell rigidity correlated with mortality, but did not improve with
      NAC. CONCLUSION: Systemic oxidative stress is increased in severe malaria.
      Treatment with NAC had no effect on outcome in patients with severe falciparum
      malaria in this setting.

PMID- 19114893
TI  - Bedside postpyloric feeding tube placement: a pilot series to validate this novel
      technique.
AB  - OBJECTIVE: Postpyloric feeding may facilitate tolerance to enteral nutrition (EN)
      and offers an alternative route of feed administration when prepyloric EN fails.
      However, this is constrained by the difficulty of establishing nasojejunal (NJ)
      tube placement, which may necessitate endoscopy or radiology with the inevitable
      delay in the instigation of treatment. A bedside technique of NJ tube insertion
      has, therefore, been developed to permit blind postpyloric intubation. The
      primary aim of this audit was to validate the success of bedside NJ tube
      placement using the described technique. Secondary end points included the time
      taken to establish EN and the value of aspirate pH as an indicator of tube tip
      placement. DESIGN: Observational. SETTING: District general hospital. PATIENTS:
      Consecutive patients requiring EN. MEASUREMENTS AND MAIN RESULTS: The time taken
      to insert the tubes, the success rates in achieving the required position, and
      the time between the decision to feed and commencement of EN were recorded. The
      pH of any aspirate obtained was related to tube tip placement. Tube position was
      confirmed radiologically before starting EN. A total of 43 NJ tubes were inserted
      in 32 patients. Successful postpyloric intubation was achieved in 35 of 43
      patients (81%). The median time for tube insertion was 18 (14-30) minutes. Time
      from the decision to feed to commencement of EN was 6 (5-18) hours. Aspirates
      were obtained from 26 of 43 (60%) intubations. Gastric aspirate pH readings were
      obtained for 19 of 43 (44%) of these intubations. Radiology reliably demonstrated
      the position of the tube tip in all cases. CONCLUSIONS: By-the-bedside NJ tube
      placement is possible in more than 80% of patients. This may overcome delays in
      the commencement of feeds resulting from other methods of postpyloric tube
      placement. The use of aspirate pH on its own is not a reliable indicator of tube
      tip position.

PMID- 19114894
TI  - Influence of increased intra-abdominal pressure on fluid responsiveness predicted
      by pulse pressure variation and stroke volume variation in a porcine model.
AB  - OBJECTIVE: Dynamic variables of fluid responsiveness such as pulse pressure
      variation (PPV) and stroke volume variation (SVV) have been shown to reliably
      predict the response to fluid administration in different patient populations.
      The influence of increased intra-abdominal pressure (IAP) on the predictive
      ability of these variables is currently under debate. Therefore, the present
      study was designed to evaluate whether PPV and SVV are suitable for predicting
      fluid responsiveness during elevated IAP. DESIGN: Prospective controlled
      experimental study. SETTING: Animal research laboratory. SUBJECTS: 14
      anesthetized and mechanically ventilated pigs. INTERVENTIONS: Pigs were studied
      at different experimental stages: normovolemia at baseline conditions, after
      induction of pneumoperitoneum (PP) by increasing IAP up to 25 mm Hg, followed by
      releasing PP and performing a fluid load with 1000 cc hydroxyl-ethyl starch 6%,
      and finally after inducing PP again. Cardiac output, stroke volume, central
      venous pressure, and pulmonary artery occlusion pressure were obtained by
      pulmonary artery thermodilution. Additionally, global end-diastolic volume (GEDV)
      was measured by transpulmonary thermodilution. PPV and SVV were monitored
      continuously by pulse contour analysis. MEASUREMENTS AND MAIN RESULTS: PP induced
      significant changes in peak airway pressure, esophageal pressure, chest wall
      compliance, SVV, PPV, central venous pressure, and pulmonary artery occlusion
      pressure independent of loading conditions. As assessed by receiver operating
      characteristic curve analysis, PPV, SVV, and GEDV accurately predicted fluid
      responsiveness before IAP was increased (area under the curve: 0.90, 0.91 and
      0.91). A PPV value of >or=11.5%, a SVV value of >or=9.5%, and a GEDV value of
      <or=963 mL accurately predicted an increase in stroke volume >or=15%. After
      increasing IAP, the ability of SVV to predict fluid responsiveness was abolished,
      whereas it was preserved with both PPV and GEDV, although the threshold value for
      PPV dramatically increased up to >or=20.5%. CONCLUSIONS: : In this animal model
      PPV and GEDV proved to be sensitive and specific predictors of fluid
      responsiveness even during increased IAP.

PMID- 19114895
TI  - Alkaline phosphatase treatment improves renal function in severe sepsis or septic
      shock patients.
AB  - OBJECTIVE: Alkaline phosphatase (AP) attenuates inflammatory responses by
      lipopolysaccharide detoxification and may prevent organ damage during sepsis. To
      investigate the effect of AP in patients with severe sepsis or septic shock on
      acute kidney injury. DESIGN AND SETTING: A multicenter double-blind, randomized,
      placebo-controlled phase IIa study (2:1 ratio). PATIENTS: Thirty-six intensive
      care unit patients (20 men/16 women, mean age 58 +/- 3 years) with a proven or
      suspected Gram-negative bacterial infection, >or=2 systemic inflammatory response
      syndrome criteria (<24 hours), and <12 hours end-organ dysfunction onset were
      included. INTERVENTION: An initial bolus intravenous injection (67.5 U/kg body
      weight) over 10 minutes of AP or placebo, followed by continuous infusion (132.5
      U/kg) over the following 23 hours and 50 minutes. MEASUREMENTS AND MAIN RESULTS:
      Median plasma creatinine levels declined significantly from 91 (73-138) to 70 (60
      92) micromol/L only after AP treatment. Pathophysiology of nitric oxide (NO)
      production and subsequent renal damage were assessed in a subgroup of 15
      patients. A 42-fold induction (vs. healthy subjects) in renal inducible NO
      synthase expression was reduced by 80% +/- 5% after AP treatment. In AP-treated
      patients, the increase in cumulative urinary NO metabolite excretion was
      attenuated, whereas the opposite occurred after placebo. Reduced excretion of NO
      metabolites correlated with the proximal tubule injury marker glutathione S
      transferase A1-1 in urine, which decreased by 70 (50-80)% in AP-treated patients
      compared with an increase by 200 (45-525)% in placebo-treated patients.
      CONCLUSIONS: In severe sepsis and septic shock, infusion of AP inhibits the
      upregulation of renal inducible NO synthase, leading to subsequent reduced NO
      metabolite production, and attenuated tubular enzymuria. This mechanism may
      account for the observed improvement in renal function.

PMID- 19114896
TI  - Antishock effect of anisodamine involves a novel pathway for activating alpha7
      nicotinic acetylcholine receptor.
AB  - OBJECTIVE: Vagus nerve stimulation inhibits proinflammatory cytokine production
      by signaling through the alpha7 nicotinic acetylcholine receptor (alpha7nAChR).
      Anisodamine, a muscarinic acetylcholine receptor antagonist, has been used
      clinically in China for treatment of various shocks, but the mechanism was poorly
      understood. Here, we tested the hypothesis whether anisodamine attained its
      antishock effect through activation of alpha7nAChR. DESIGN: : Randomized and
      controlled in vitro and in vivo study. SETTINGS: Research laboratory and animal
      facility rooms. SUBJECTS: Sprague-Dawley rats, Kunming mice, alpha7nAChR
      deficient mice, and RAW264.7 cells. INTERVENTIONS: Sprague-Dawley rats were
      injected with lipopolysaccharide (LPS) (15 mg/kg, intravenous) to induce septic
      shock. Methyllycaconitine, a selective alpha7nAChR antagonist, was administered
      (10 mg/kg, intraperitoneal) 10 minutes before anisodamine (10 mg/kg,
      intravenous). Mean arterial pressure was monitored and cytokines were analyzed 2
      hours after the onset of LPS. In vagotomized mice and alpha7nAChR-deficient mice,
      the antishock effect of anisodamine was appraised, respectively. RAW264.7 cells
      were stained by fluorescein isothiocyanate- labeled-alpha-bungarotoxin and the
      fluorescence intensity was observed. Mice peritoneal macrophages were pretreated
      and stimulated with LPS, and tumor necrosis factor (TNF)-alpha in the supernatant
      was measured by enzyme-linked immunosorbent assay. MEASUREMENTS AND MAIN RESULTS:
      Methyllycaconitine significantly antagonized the beneficial effect of anisodamine
      on mean arterial pressure and TNF-alpha, interleukin-1beta expression in response
      to LPS. The antishock effects of anisodamine were markedly attenuated in
      vagotomized mice and alpha7nAChR-deficient mice. In vitro, anisodamine
      significantly augmented the effect of acetylcholine on fluorescence intensity
      stained with fluorescein isothiocyanate-labeled-alpha-bungarotoxin and TNF-alpha
      production stimulated with LPS. CONCLUSION: These findings demonstrate that the
      antishock effect of anisodamine is intimately linked to alpha7nAChR-dependent
      anti-inflammatory pathway.

PMID- 19114897
TI  - C1-inhibitor attenuates neurobehavioral deficits and reduces contusion volume
      after controlled cortical impact brain injury in mice.
AB  - OBJECTIVE: The aim of the study was to evaluate the effects of C1-inhibitor (C1
      INH), an endogenous inhibitor of complement and kinin systems, on neurobehavioral
      and histological outcome following controlled cortical impact brain injury.
      DESIGN: Experimental prospective randomized study in mice. SETTING: Experimental
      laboratory. SUBJECTS: Male C57Bl/6 mice (n = 81). INTERVENTIONS: Mice were
      subjected to controlled cortical impact brain injury followed by an intravenous
      bolus of either C1-INH (15 U either at 10 minutes or 1 hour postinjury) or saline
      (equal volume, 150 microl at 10 minutes postinjury). Sham-operated mice received
      identical surgery and saline injection without brain injury. Neurological motor
      function was evaluated weekly for 4 weeks using the Composite Neuroscore.
      Cognitive function was evaluated at 4 weeks postinjury using the Morris Water
      Maze. Histological outcome was performed by measuring the contusion volume at 1
      week and 4 weeks postinjury. MEASUREMENTS AND MAIN RESULTS: Brain-injured mice
      receiving C1-INH at 10 minutes postinjury showed attenuated motor deficits,
      cognitive dysfunction and reduced contusion volume compared to brain-injured mice
      receiving saline. Mice receiving C1-INH at 1 hour postinjury showed reduced motor
      deficits compared to brain-injured mice receiving saline, but no significantly
      different cognitive and histological outcome. Immunohistochemical analysis showed
      that 20 minutes after infusion, C1-INH was localised on endothelial cells and in
      brain tissue surrounding brain capillaries of the injured hemisphere. CONCLUSION:
      Our results show that post-traumatic administration of C1-INH attenuates neuro
      behavioral deficits and histological damage associated with traumatic brain
      injury.

PMID- 19114898
TI  - The thiazolidinedione ciglitazone reduces bacterial outgrowth and early
      inflammation during Streptococcus pneumoniae pneumonia in mice.
AB  - OBJECTIVE: Thiazolidinediones (TZDs) are synthetic agonists for the peroxisome
      proliferator-activating receptor-gamma receptor and are currently in use as oral
      glucose-lowering drugs. TZDs have immune-modulating effects in vitro and in vivo.
      Because patients with type 2 diabetes have an increased risk for pneumonia, we
      evaluated the influence of ciglitazone, a TZD, on markers of inflammation and
      outcome during pneumonia caused by Streptococcus pneumoniae. DESIGN: In vivo
      animal study and in vitro study. SETTING: University research laboratory.
      SUBJECTS: Female C57Bl/6 mice and murine alveolar macrophage-like MH-S cells.
      INTERVENTIONS: C57Bl/6 mice were inoculated with 10 colony-forming units of S.
      pneumoniae intranasally. The following interventions were studied: 1) vehicle at
      t = 0; 2) ciglitazone 5 mg/kg intraperitoneally at t = 0; and 3) ciglitazone 5
      mg/kg intraperitoneally at t = 0 and 24 hours. Mice were killed at either 24 or
      48 hours after infection. Additionally, phagocytosis and killing of S. pneumoniae
      by MH-S cells were assessed in vitro. MEASUREMENTS AND MAIN RESULTS: Single
      treatment with ciglitazone reduced bacterial loads at 24 hours but not at 48
      hours, whereas repeated ciglitazone treatment did diminish bacterial loads at 48
      hours. After 24 hours, cytokine levels in lung homogenate were lower in single
      dose ciglitazone-treated mice; however, after 48 hours, there was no difference
      in lung cytokines between any of the experimental groups. Repeated ciglitazone
      treatment was associated with less pulmonary inflammation, as judged by
      histologic examination. On both time points, there was no difference in plasma
      cytokine levels or lung myeloperoxidase levels between experimental groups. In an
      additional experiment, ciglitazone treatment (given once daily) tended to reduce
      mortality. Ciglitazone did not influence phagocytosis or killing of S. pneumoniae
      by murine alveolar macrophages. CONCLUSIONS: Ciglitazone reduces bacterial
      outgrowth and local inflammation at least during the early stage of S. pneumoniae
      pneumonia in mice.

PMID- 19114899
TI  - Bbeta15-42 (FX06) reduces pulmonary, myocardial, liver, and small intestine
      damage in a pig model of hemorrhagic shock and reperfusion.
AB  - OBJECTIVE: The fibrin-derived peptide Bbeta15-42 (also called FX06) has been
      shown to reduce myocardial infarct size following ischemia/reperfusion.
      Hemorrhagic shock (HS) followed by volume resuscitation represents a similar
      scenario, whereby a whole organism is vulnerable to reperfusion injury. DESIGN:
      We subjected male farm-bred landrace pigs ( approximately 30 kg) to HS by
      withdrawing blood to a mean arterial pressure of 40 mm Hg for 60 minutes. Pigs
      were then resuscitated with shed blood and crystalloids for 60 minutes, and at
      this time, FX06 (2.4 mg/kg, n = 8) or vehicle control (phosphate buffered saline;
      2.4 mg/kg, n = 7) was injected as an intravenous bolus. SETTING: University
      hospital laboratory. SUBJECTS: Anesthetized male farm-bred landrace pigs.
      MEASUREMENTS AND MAIN RESULTS: Data are presented as mean +/- sd. Five hours
      after resuscitation, controls presented acute lung injury (Pao2/Fio2-ratio <300
      mm Hg; extra-vascular lung water index (marker for lung injury): 9.0 +/- 1.8
      mL/kg) and myocardial dysfunction/damage (cardiac index: 4.3 +/- 0.25 L/min/m;
      stroke volume index: 30 +/- 6 mL/m; cardiac TnT levels: 0.58 +/- 0.25 ng/mL). In
      contrast, FX06-treated animals showed significantly improved pulmonary and
      circulatory function (Pao2/Fio2-ratio >*400 mm Hg; extra-vascular lung water
      index: *5.2 +/- 2.1 mL/kg, cardiac index: *6.3 +/- 1.4 L/min/m; stroke volume
      index: *51 +/- 11 mL/m; cardiac TnT levels: *0.11 +/- 0.09 ng/mL; *p < 0.05).
      Also, tissue oxygenation (tpO2; mm Hg) was significantly improved during
      reperfusion in FX06-treated pigs when compared with controls (liver 51 +/- 4 vs.
      *65 +/- 4; serosa 44 +/- 5 vs. *55 +/- 7; mucosa 14 +/- 4 vs. *26 +/- 4).
      Finally, FX06 reduced accumulation of myeloperoxidase-positive cells (mainly
      neutrophils) in myocardium, liver, and small intestine and reduced interleukin-6
      plasma levels (*p < 0.05; compared with controls). CONCLUSION: We conclude that
      in a pig model of HS and reperfusion, administration of FX06 during reperfusion
      protects shock- susceptible organs such as heart, lung, liver, and small
      intestine.

PMID- 19114900
TI  - Admission of incompetent patients to intensive care: doctors' responsiveness to
      family wishes.
AB  - OBJECTIVE: When a patient is incompetent, the family is often considered to be a
      natural surrogate. The doctors' responsiveness to family wishes may vary. We
      explored if doctors' personal characteristics were associated with responsiveness
      to the relatives' wishes when admission to the intensive care unit (ICU) is
      considered. METHODS: In a mail survey, we asked all Swiss ICU doctors to decide
      on the admission of a hypothetical incompetent patient presenting with hemolytic
      uremic syndrome. Each participant was randomly allocated to a version of the
      scenario in which the family asked either that "everything be done" or that the
      patient be "spared useless suffering." MAIN RESULTS: Overall, 232 (60.9%)
      questionnaires were returned. When the family asked that "everything be done,"
      60% of doctors chose to admit the hypothetical patient, but when the family asked
      that she be spared useless suffering, only 39% did so (odds ratio [OR] 2.6,
      confidence interval 1.5-4.6). This OR captures responsiveness to family wishes.
      It varied across subgroups of ICU doctors. Characteristics associated with
      greater responsiveness to family wishes were older age (OR 6.0 vs. 1.2, p =
      0.002), nonuniversity work setting (OR 4.2 vs. 1.0, p = 0.012), less time devoted
      to intensive care practice (OR 4.0 vs. 1.5, p = 0.036), and greater self
      confidence in ethical knowledge (OR 3.4 vs. 1.7, p = 0.044). CONCLUSIONS: Older
      doctors and those working in regional hospitals were more responsive to family
      wishes when assessing an incompetent patient for ICU admission. These findings
      emphasize the need for effective advance care planning.

PMID- 19114901
TI  - A microbiological survey of bicarbonate-based replacement circuits in continuous
      veno-venous hemofiltration.
AB  - OBJECTIVE: The potential for clinically significant transfer of pyrogen-inducing
      material in dialysate and substitution fluids is well recognized in the setting
      of chronic hemodialysis and hemodiafiltration and has led to the establishment of
      strict standards for microbiological purity. Preliminary evidence has indicated
      the potential for fluid contamination in continuous renal replacement therapy,
      and although the scale of the problem in contemporary, industry-standard
      equipment is unclear. We aimed to define the microbial integrity of modern
      continuous veno-venous hemofiltration (CVVH) replacement fluid circuitry. DESIGN:
      Twenty-four CVVH replacement fluid circuits (mean lifespan, 34.2 hours; range, 4
      86) were studied at completion of therapy. SETTING: The integrated critical care
      unit and cardiothoracic intensive care unit of the Freeman Hospital, Newcastle
      upon Tyne, United Kingdom, between January and August 2007. SUBJECTS: Patients
      with renal failure receiving treatment with CVVH. INTERVENTIONS: Nil.
      MEASUREMENTS: Culture and endotoxin assays of replacement fluid, culture of
      endoluminal swabs, and electron microscopy of harvested tubing. MAIN RESULTS: Of
      the 24 replacement fluid cultures, nine (mean lifespan 32.8 hours, range 5-79)
      breached European Pharmacopoeia standards for ultrapure water (<0.1 colony
      forming units/mL). One of 24 endotoxin measurements breached European
      Pharmacopoeia standards (<0.03 endotoxin units/mL). Internal tubing cultures were
      negative, but electron microscopy revealed 13 of the 24 collected tubing samples
      to be contaminated with biofilm. Only seven of the 24 studied circuits proved to
      be free from microbial contamination. CONCLUSIONS: We have confirmed frequent
      breaches of microbial integrity in industry-standard, bicarbonate-based CVVH,
      indicating the potential for added risk to the vulnerable, critically ill
      patient. These findings are of particular concern given the need for systemic
      infusion of replacement fluid. Measures to reduce the levels of contamination and
      their impact are discussed.

PMID- 19114902
TI  - The vasopressin and copeptin response to infection, severe sepsis, and septic
      shock.
AB  - OBJECTIVE: To compare the course of arginine vasopressin (AVP) and copeptin
      plasma concentrations between patients with infection, severe sepsis, and septic
      shock. DESIGN: Prospective, closed-cohort study. SETTING: Twelve-bed general and
      surgical intensive care unit and 33-bed internal medicine ward in a university
      hospital. PATIENTS: Ten patients with infection, 22 with severe sepsis, and 28
      with septic shock. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS:
      Hemodynamic, laboratory and clinical data were recorded daily during the first 7
      days after intensive care unit or hospital admission. Parallel thereto, blood was
      withdrawn to determine plasma AVP (radioimmunoassay) and copeptin
      (immunoluminometric assay) concentrations. Standard tests, a mixed effects model,
      and a linear regression analysis were used for statistical analysis. The AVP
      response was different between the three study groups (p < 0.001) but did not
      change over time (p = 0.12). Although patients with severe sepsis and septic
      shock had higher AVP levels than did patients with infection (both p < 0.001), no
      difference in AVP concentrations was seen between severe sepsis and septic shock
      patients (p = 0.98). No difference in AVP was observed between survivors and
      nonsurvivors at day 28 (p = 0.87). In patients with severe sepsis, serum
      osmolarity (p < 0.001), arterial pH (p = 0.001), lactate (p < 0.001), and Pao2 (p
      = 0.04) were associated with the course of AVP plasma levels, whereas it was
      serum osmolarity alone in patients with septic shock (p = 0.03). Plasma AVP
      concentrations correlated with copeptin (r = .614, p < 0.001), but this
      correlation was influenced by continuous veno-venous hemofiltration (p = 0.002).
      CONCLUSIONS: Severe sepsis induced a stronger AVP response than infection without
      systemic inflammation. However, the lack of a difference in AVP plasma
      concentrations between patients with and without shock indicates that the AVP
      system does not function normally in severe sepsis. Our data support the
      hypothesis that impaired AVP response is at least partially responsible for the
      failure to restore vascular tone in septic shock.

PMID- 19114903
TI  - Physical therapy utilization in intensive care units: results from a national
      survey.
AB  - OBJECTIVE: Patients who survive admission to the intensive care unit (ICU)
      commonly complain of fatigue, weakness, and poor functional status. This study
      sought to determine the utilization of inpatient physical therapy (PT) for
      patients recovering from critical illness. DESIGN: Surveys were mailed to 984
      physical therapists from across the United States. Each survey included questions
      concerning staffing and availability of physical therapists for ICU patients, and
      the utilization of PT for six patient scenarios requiring ICU admission and
      mechanical ventilation. MAIN RESULTS: Overall, 482 physical therapists completed
      their survey. The majority of hospitals (89%) at which the physical therapists
      were employed require a physician consultation to initiate PT for ICU patients.
      Established hospital criteria for the initiation of PT in the ICU were present at
      only 10% of the hospitals. Community hospitals were more likely to routinely
      provide PT on weekends compared with academic hospitals (p = 0.03). The
      likelihood of routine PT involvement varied significantly with the clinical
      scenario (highest 87% status postcerebrovascular accident, lowest 64% chronic
      obstructive pulmonary disease, p < 0.001). The most common types of PT that would
      be performed on these critically ill patients were functional mobility retraining
      and therapeutic exercise. The type of PT identified by the physical therapists as
      having the most positive impact also significantly varied according to the
      clinical scenario (p < 0.001). CONCLUSIONS: PT is commonly administered to ICU
      patients during the recovery from critical illness in the United States. However,
      the frequency and the type of PT significantly varies based on the type of
      hospital and the clinical scenario.

PMID- 19114904
TI  - Interactive video instruction improves the quality of dispatcher-assisted chest
      compression-only cardiopulmonary resuscitation in simulated cardiac arrests.
AB  - OBJECTIVE: Bystander cardiopulmonary resuscitation (CPR) significantly improves
      survival of cardiac arrest victims. Dispatch assistance increases bystander CPR,
      but the quality of dispatcher-assisted CPR remains unsatisfactory. This study was
      conducted to assess the effect of adding interactive video communication to
      dispatch instruction on the quality of bystander chest compressions in simulated
      cardiac arrests. DESIGN: A randomized controlled study with a scenario developed
      to simulate cardiac arrest in a public place. SETTING: The victim was simulated
      by a mannequin and the cell phone for dispatch assistance was a video cell phone
      with both voice and video modes. Chest compression-only CPR instruction was used
      in the dispatch protocol. SUBJECTS: Ninety-six adults without CPR training within
      5 years were recruited. INTERVENTIONS: The subjects were randomized to receive
      dispatch assistance on chest compression with either voice instruction alone
      (voice group, n = 53) or interactive voice and video demonstration and feedback
      (video group, n = 43) via a video cell phone. MEASUREMENTS AND MAIN RESULTS:
      Performance of chest compression-only CPR throughout the scenario was videotaped.
      The quality of CPR was evaluated by reviewing the videos and mannequin reports.
      Chest compressions among the video group were faster (median rate 95.5 vs. 63.0
      min-1, p < 0.01), deeper (median depth 36.0 vs. 25.0 mm, p < 0.01), and of more
      appropriate depth (20.0% vs. 0%, p < 0.01). The video group had more "hands-off"
      time (5.0 vs. 0 second, p < 0.01), longer time to first chest compression (145.0
      vs. 116.0 seconds, p < 0.01) and total instruction time (150.0 vs. 121.0 seconds,
      p < 0.01). CONCLUSION: The addition of interactive video communication to
      dispatcher-assisted chest compression-only CPR initially delayed the commencement
      of chest compressions, but subsequently improved the depth and rate of
      compressions. The benefit was achieved mainly through real-time feedback.

PMID- 19114905
TI  - Arrhythmias and heart rate variability during and after therapeutic hypothermia
      for cardiac arrest.
AB  - OBJECTIVE: To evaluate the effects of therapeutic hypothermia (HT) of 33 degrees
      C after cardiac arrest (CA) on cardiac arrhythmias, heart rate variability (HRV),
      and their prognostic value. DESIGN: Prospective, comparative substudy of a
      randomized controlled trial of mild HT after out-of-hospital CA, the European
      Hypothermia After Cardiac Arrest study. SETTING: Intensive care unit of a
      tertiary referral hospital (Helsinki University Hospital). PATIENTS: Seventy
      consecutive adult patients resuscitated from out-of-hospital ventricular
      fibrillation were randomly assigned either to therapeutic HT of 33 degrees C or
      normothermia. INTERVENTIONS: Patients randomized to HT were cooled with an
      external cooling device for 24 hours and then allowed to rewarm slowly during 12
      hours. In the normothermia group, the core temperature was kept <38 degrees C by
      antipyretics and physical means. All patients received standard intensive care
      for at least 2 days. MEASUREMENTS AND MAIN RESULTS: Twenty-four hour ambulatory
      electrocardiography recordings were performed at 0-24 hours, at 24-48 hours, and
      at 14 days. The clinical outcome was assessed at 6 months after CA. The
      occurrence of premature ventricular beats was increased in the HT-treated group
      during the first two recordings, with no difference in the number of ventricular
      tachycardia or ventricular fibrillation episodes. All HRV values were
      significantly higher during the HT (p < 0.01), but no differences were observed 2
      weeks later. In multivariate analysis, only shorter delay to restoration of
      spontaneous circulation (p = 0.009) and the sd of individual normal-to-normal
      intervals >100 msec of the 24-48-hour recording in the HT group (p = 0.018)
      predicted good outcome. CONCLUSIONS: The use of therapeutic HT of 33 degrees C
      for 24 hours after CA was not associated with an increase in clinically
      significant arrhythmias. Preserved 24 to 48-hour HRV may be a predictor of
      favorable outcome in patients with CA treated with HT.

PMID- 19114906
TI  - Intra-abdominal pressure effects on porcine thoracic compliance in
      weightlessness: implications for physiologic tolerance of laparoscopic surgery in
      space.
AB  - OBJECTIVE: Laparoscopic surgery (LS) is envisioned as an option for spaceflight,
      but requires intra-abdominal hypertension (IAH) to create the surgical domain.
      Prolonged weightlessness induces physiologic deconditioning that questions the
      ability of ill or injured astronauts to tolerate IAH. On earth, IAH results in
      marked ventilatory embarrassment. As there has been no previous study of
      physiologic changes related to LS in weightlessness, we studied anesthetized pigs
      in parabolic flight. DESIGN: Parabolic flight research laboratory. SUBJECTS: Five
      anesthetized Yorkshire pigs. INTERVENTIONS: Subjects were transported from an
      animal care facility and secured aboard an aircraft capable of generating
      hypergravity and weightlessness. Mechanical ventilation was performed using
      pressure control and positive end-expiratory pressure at 15 and 2 cm H2O,
      respectively; rate 12 breaths/min. Three abdominal conditions were used during
      LS: insufflation to produce IAH, abdominal wall retraction (AWR), and no
      abdominal wall manipulation (baseline). During each parabola breath by breath
      tidal volumes (Vt) were recorded by a transport ventilator (HT-50 Newport
      Medical). MEASUREMENTS AND MAIN RESULTS: Least square means (LS-means) of weight
      corrected Vt (milliliter per kilogram) by gravity (g) and abdominal condition
      were determined using a mixed effects model for repeated measures analysis.
      Increasing gravity (g) consistently reduced Vt (p = 0.0011) as did insufflation
      (p < 0.0001). In 1g, Vt (LS-mean 13.7, 95% confidence interval [CI]: 12.4-15.0)
      was relatively unaffected by AWR (LS-mean 12.8, 95% CI: 11.5-14.00), but markedly
      decreased by IAH (LS-mean 10.00, 95% CI: 8.9-11.1), an effect accentuated in
      hypergravity (LS-mean 8.1, 95% CI: 6.4-9.8). In weightlessness, Vt reduction
      during insufflation was near obviated (LS-mean 12.3, 95% CI: 10.6-14.1), and AWR
      regularly but inconsistently increased the Vt above 1g baseline (LS-mean 13.7,
      95% CI: 11.7-15.8). CONCLUSIONS: Weightlessness protects against thoracic
      compliance changes that are inherent in IAH during induced pneumoperitoneum in
      gravity. The technique-related physiologic cost of performing LS in space
      deconditioned astronauts should be incorporated into design concepts for space
      surgery systems.

PMID- 19114907
TI  - Effects of early vital capacity maneuver on respiratory variables during
      multivessel off-pump coronary artery bypass graft surgery.
AB  - OBJECTIVES: Despite avoiding cardiopulmonary bypass, similar degrees of pulmonary
      impairment compared with on-pump coronary artery bypass surgery have been
      demonstrated in patients undergoing off-pump coronary artery bypass graft surgery
      (OPCAB) compared with on-pump coronary artery bypass surgery. To investigate the
      effects of an early vital capacity maneuver (VCM) on intrapulmonary shunt
      (Qs/Qt), oxygenation, and pulmonary outcome in OPCAB. DESIGN: Prospective,
      randomized, controlled, double-blind clinical trial. SETTING: Cardiothoracic
      operating room and intensive care unit (ICU) of a university hospital. PATIENTS:
      Fifty patients scheduled for OPCAB were randomized to treatment with VCM or none.
      INTERVENTIONS: After sternotomy, VCM was performed by inflating the lungs to 40
      cm H2O and holding this pressure for 10 seconds. MEASUREMENTS AND MAIN RESULTS:
      Qs/Qt, Pao2/Fio2 (P/F) ratio, and dynamic and static pulmonary compliances were
      measured before induction of anesthesia (T0), 15 minutes after tracheal
      intubation (T1), during Y-graft construction (T2), 15 minutes after completion of
      grafting (T3), 15 minutes after sternal closure (T4), and 3 hours after arrival
      at the ICU (T5). Qs/Qt was lower and P/F ratio was higher in the VCM group at T2
      through T5. Pulmonary compliances were also higher in the VCM group at T4 and T5.
      Patients in the VCM group were extubated earlier. CONCLUSIONS: The beneficial
      effects of an early VCM on Qs/Qt persisted into the period of ICU care, with an
      improvement in P/F ratio and preserved pulmonary compliances, leading to a
      shorter time to extubation.

PMID- 19114908
TI  - Tight glycemic control may favor fibrinolysis in patients with sepsis.
AB  - OBJECTIVE: To investigate whether tight glycemic control, in patients with
      sepsis, may restore a normal fibrinolysis by lowering plasminogen activator
      inhibitor (PAI)-1 levels. DESIGN: Prospective randomized clinical trial. SETTING:
      Three Italian university hospital intensive care units. PATIENTS: Ninety patients
      with severe sepsis/septic shock. INTERVENTIONS: Patients were randomized to
      receive either tight glycemic control (treatment group, target glycemia, 80-110
      mg/dL) or conventional glycemic control (control group, target glycemia, 180-200
      mg/dL). MEASUREMENTS: Inflammation, coagulation, and fibrinolysis markers were
      assessed, along with Sepsis-related Organ Failure Assessment scores, >28 days.
      MAIN RESULTS: In the whole population, at enrolment, inflammation and coagulation
      were activated in >80 of 90 patients, whereas fibrinolysis, as assessed by PAI-1
      activity and concentration, was impaired in only 34 patients. The extent of the
      inflammatory reaction or of the coagulation activation was unrelated to outcome.
      In contrast, 90-day mortality rate of the 34 patients in whom fibrinolysis was
      definitely inhibited at study entry was twice that of the 56 patients in whom
      fibrinolysis was intact (44% vs. 21%, p = 0.02). After randomization, during the
      study, daily glycemia averaged 112 +/- 23 mg/dL in the treatment group and 159 +/
      31 mg/dL in controls (p < 0.001), with total daily administered insulin 57 +/-
      59 IU and 36 +/- 44 IU, respectively (p < 0.001). A small, but significant,
      enhancement of fibrinolysis could be observed in the treatment group, as
      indicated by the time course of PAI-1 activity (p < 0.001), PAI-1 concentration
      (p = 0.004), and plasmin-antiplasmin complexes (p < 0.001). Morbidity, rated with
      the Sepsis-related Organ Failure Assessment score, became significantly lower (p
      = 0.03) in the treatment group. CONCLUSIONS: Fibrinolysis inhibition, in severe
      sepsis/septic shock, seems to have a relevant pathogenetic role. In this context,
      tight glycemic control seems to reduce, with time, the fibrinolytic impairment
      and morbidity.

PMID- 19114909
TI  - Furosemide does not improve renal recovery after hemofiltration for acute renal
      failure in critically ill patients: a double blind randomized controlled trial.
AB  - OBJECTIVE: To study the potential beneficial role of furosemide in resolving
      renal failure after hemofiltration in mechanically ventilated critically ill
      patients. DESIGN: Single-center randomized, double blind, placebo-controlled
      study. SETTING: A 13-bed mixed intensive care unit (ICU) in a teaching hospital.
      PATIENTS: Patients who had been treated with continuous venovenous hemofiltration
      were included. INTERVENTIONS: After the end of continuous venovenous
      hemofiltration, the urine of the first 4 hours was collected for measuring
      creatinine clearance. Patients were subsequently randomized for furosemide (0.5
      mg/kg/hr) or placebo by continuous infusion. To prevent hypovolemia, the rate of
      fluid infusion was adapted every hour and was set as the urinary production of
      the previous hour. MEASUREMENTS AND MAIN RESULTS: End points were renal recovery
      (creatinine clearance more than 30 mL/min or stable serum creatinine without
      renal replacement therapy) in the ICU and in the hospital. Seventy-two patients
      were included and 71 were eligible for the analysis. The 36 furosemide-treated
      patients had a significantly increased urinary volume compared with the 35
      placebo-treated patients (median 247 mL/hr (interquartile range [IQR] 774 mL/hr)
      vs. 117 mL/hr (IQR 158 mL/hr), p = 0.003) and greater sodium excretion (median 73
      mmol/L (IQR 48) vs. 37 (IQR 48) mmol/L, p = 0.001). In the furosemide group 25
      patients and in the placebo group 27 patients showed recovery of renal function
      at ICU discharge (p = 0.46). Two patients of the furosemide group needed long
      term dialysis dependency (p = 0.23). CONCLUSION: Furosemide by continuous
      infusion in the recovery phase of hemofiltration-dependent acute kidney failure
      did increase urinary volume and sodium excretion but did not lead to a shorter
      duration of renal failure or more frequent renal recovery.

PMID- 19114910
TI  - Critical care checklists, the Keystone Project, and the Office for Human Research
      Protections: a case for streamlining the approval process in quality-improvement
      research.
AB  - Checklists have been recently promulgated as a method to enhance patient safety
      and improve outcomes for critically ill patients. Specifically, recent work
      performed by researchers from the Johns Hopkins Medical Institutions has
      demonstrated that the addition of checklists to usual care in the intensive care
      unit is associated with a decrease in the incidence of catheter-related
      bloodstream infections. Initially evaluated at the institutional level, this
      effort has been successfully expanded to the state level as part of the Michigan
      Keystone Project. Although this work has recently received significant positive
      attention in the lay press, the Office for Human Research Protections--as they
      felt that this was a research project requiring Institutional Review Board
      approval and informed consent--put the data collection on hold for lack of
      approval by the Institutional Review Board at the participating hospitals in
      Michigan as well as for not having obtained informed consent from each patient
      and clinician involved in the project. This article documents the recent events
      surrounding the Keystone Project and the response to the actions taken by the
      Office for Human Research Protections in the lay press and the new media
      (Internet and blogs), articulates how a determination can be made if a project is
      quality-improvement, human-subjects research, or both, and proposes some
      solutions to create a structured approach to this kind of research in the future.

PMID- 19114911
TI  - Cerebral desaturation during cardiac arrest: its relation to arrest duration and
      left ventricular pump function.
AB  - OBJECTIVE: To determine the impact of brief periods of cardiac arrest (CA) on
      regional cerebral oxygen saturation (rSO2) in patients with low left ventricular
      ejection fraction (LVEF <30%). DESIGN: Prospective observational study. SETTING:
      Cardiac surgery room at a university hospital. PATIENTS: Seventy-seven
      consecutive patients undergoing elective implantation of a
      cardioverter/defibrillator in monitored anesthesia care. According to
      preoperative assessments, left ventricular function was classified as normal
      (LVEF >50%), moderately impaired (LVEF 30%-50%), or severely reduced (LVEF <30%).
      INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: rSO2 was determined during
      threshold testing with concomitant induction of CA. In patients with LVEF <30%,
      mean baseline rSO2 (59%) was already below the lower range of normal despite
      normal arterial blood pressure, heart rate, and arterial oxygen saturation. rSO2
      increased by 6% after 6 L/min oxygen insufflation (p < 0.05) and dropped again in
      each group after CA, reaching a nadir after successful defibrillation. Patients
      with LVEF <30% and baseline rSO2 <63% exhibited the lowest values. They also
      showed the highest incidence (11%) of critical cerebral desaturations (i.e., >20%
      drop from baseline or rSO2 value <50%). rSO2 in patients with LVEF <30% was
      always below that determined in patients with LVEF >30% (p < 0.05). There was a
      strong correlation between rSO2 values before CA and rSO2 nadir (p < 0.05). The
      drop in rSO2 was only moderately related to the brief CAs (p < 0.05). CONCLUSION:
      These findings demonstrate that severely compromised left ventricular pump
      function is associated with diminished rSO2. As these patients seem to be more
      susceptible to critical desaturations, they may be prone to severe tissue
      hypoxemia unless adequate oxygen delivery is reestablished rapidly. This may
      contribute to the poor neurologic outcome after successful resuscitation in
      patients with LVEF <30%.

PMID- 19114912
TI  - Citrate anticoagulation for continuous venovenous hemofiltration.
AB  - OBJECTIVE: Continuous venovenous hemofiltration (CVVH) is applied in critically
      ill patients with acute renal failure for renal replacement. Heparins used to
      prevent circuit clotting may cause bleeding. Regional anticoagulation with
      citrate reduces bleeding, but has metabolic risks. The aim was to compare the
      safety and efficacy of the two. DESIGN: Randomized, nonblinded, controlled single
      center trial. SETTING: General intensive care unit of a teaching hospital.
      PATIENTS: Adult critically ill patients needing CVVH for acute renal failure and
      without an increased bleeding risk. INTERVENTIONS: Regional anticoagulation with
      citrate or systemic anticoagulation with the low-molecular weight heparin
      nadroparin. MEASUREMENTS AND MAIN RESULTS: End points were adverse events
      necessitating discontinuation of study anticoagulant, transfusion, metabolic and
      clinical outcomes, and circuit survival. Of the 215 randomized patients, 200
      received CVVH per protocol (97 citrate and 103 nadroparin). Adverse events
      required discontinuation of citrate in two patients (accumulation and clotting)
      of nadroparin in 20 (bleeding and thrombocytopenia) (p < 0.001). Bleeding
      occurred in 6 vs. 16 patients (p = 0.08). The median number of red blood cell
      units transfused per CVVH day was 0.27 (interquartile range, 0.0-0.63) for
      citrate, 0.36 (interquartile range, 0-0.83) for nadroparin (p = 0.31). Citrate
      conferred less metabolic alkalosis (p = 0.001) and lower plasma calcium (p <
      0.001). Circuit survival was similar. Three-month mortality on intention-to-treat
      was 48% (citrate) and 63% (nadroparin) (p = 0.03), per protocol 45% and 62% (p =
      0.02). Citrate reduced mortality in surgical patients (p = 0.007), sepsis (p =
      0.01), higher Sepsis-Related Organ Failure Assessment score (p = 0.006), and
      lower age (p = 0.009). CONCLUSIONS: The efficacy of citrate and nadroparin
      anticoagulation for CVVH was similar, however, citrate was safer. Unexpectedly,
      citrate reduced mortality. Less bleeding could only partly explain this benefit,
      less clotting could not. Post hoc citrate appeared particularly beneficial after
      surgery, in sepsis and severe multiple organ failure, suggesting interference
      with inflammation.

PMID- 19114913
TI  - Immunosuppression associated with interleukin-1R-associated-kinase-M upregulation
      predicts mortality in Gram-negative sepsis (melioidosis).
AB  - OBJECTIVES: Sepsis is associated with immunosuppression (characterized by a
      reduced capacity of circulating monocytes to release proinflammatory cytokines),
      which has been implicated in late mortality. Melioidosis, caused by the Gram
      negative bacterium Burkholderia pseudomallei, is an important cause of community
      acquired sepsis in Southeast Asia with a mortality of up to 40%. Previous in
      vitro and murine studies have suggested a key role for the so-called negative
      regulators of the toll-like receptor (TLR) signaling pathway in
      immunosuppression. In this study, we investigated the expression of these
      negative TLR regulators in patients with septic melioidosis in association with
      the responsiveness of peripheral blood leukocytes of these patients to
      lipopolysaccharide and B. pseudomallei. DESIGN: Ex vivo study. SETTING: Academic
      research laboratory. PATIENTS: Thirty-two healthy controls and 34 patients with
      sepsis caused by B. pseudomallei. INTERVENTIONS: None. MEASUREMENTS: 1) Plasma
      cytokine levels; 2) ex vivo cytokine production capacity of whole blood; and 3)
      purified mononuclear cell-derived messenger RNA (mRNA) levels of key inhibitory
      molecules of the TLR-signaling cascade were investigated. MAIN RESULTS: In
      accordance with an immunosuppressed state, whole blood of patients demonstrated a
      strongly decreased capacity to release the proinflammatory cytokines tumor
      necrosis factor-[alpha], interleukin-1[beta], and the chemokine interleukin-8
      after ex vivo stimulation with lipopolysaccharide or B. pseudomallei. Analysis of
      myeloid-differentiation-88-short, interleukin-1R-associated-kinase (IRAK)-M, IRAK
      1, suppressor-of-cytokine signaling-3, Src-homology-2-domain-containing inositol
      5-phosphatase-1, single-immunoglobulin-interleukin-1R-related-molecule, and A20
      mRNA expression in purified mononuclear cells showed decreased IRAK-1 and
      elevated IRAK-M expression in patients with septic melioidosis. Immunosuppression
      was correlated with mortality; furthermore, patients who eventually died had
      higher IRAK-M mRNA levels on admission than the patients who survived.
      CONCLUSIONS: Immunosuppression in sepsis caused by B. pseudomallei is associated
      with an upregulation of IRAK-M and an indicator of poor outcome.

PMID- 19114914
TI  - The impact of clinically undiagnosed injuries on survival estimates.
AB  - OBJECTIVES: Missed injury diagnoses may cause potentially preventable deaths. To
      estimate the effect of clinically undiagnosed injuries on injury-specific
      survival estimates and the accuracy of an injury severity score. To also estimate
      the potentially preventable mortality attributable to these injuries. DESIGN,
      SETTING, AND PATIENTS: In a nation-wide, population-based study, data were
      collected from all hospital admissions for injuries in Sweden between 1998 and
      2004. We studied 8627 deaths in hospital among 598,137 incident hospital
      admissions. MEASUREMENTS AND MAIN RESULTS: New specific-injury categories were
      added in 7.4% (95% confidence interval [CI] 6.8-8.0) of all deaths with an
      autopsy rate of 24.2%. It was estimated that this proportion would have increased
      to 25.1% (95% CI 23.0-27.2), if all deaths had been autopsied. The most
      pronounced effect of clinically undiagnosed injuries was found for internal organ
      injury in the abdomen or pelvis, where they reduced the estimated survival from
      0.83 to 0.69 (95% CI for the difference: 0.09-0.20). Autopsy diagnoses also
      revealed substantial bias of survival estimates for vascular injuries in the
      thorax and crush injuries to the head. The performance of the International
      Classification of Diseases Injury Severity Score improved when autopsy diagnoses
      were added to hospital discharge diagnoses. The maximum proportion of injury
      deaths attributable to missed injuries was estimated to be 6.5%. CONCLUSIONS:
      Maintaining a high autopsy rate and merging accurate hospital discharge data and
      autopsy data are effective ways to improve the accuracy of survival estimates and
      mortality prediction models, and to estimate mortality attributable to diagnostic
      failures.

PMID- 19114915
TI  - Early blood glucose control and mortality in critically ill patients in
      Australia.
AB  - OBJECTIVE: To measure temporal trends in blood glucose (BG) control and describe
      their association with hospital mortality in a cohort of critically ill patients
      from Australia. DESIGN: Interrogation of prospectively collected data from the
      Australia New Zealand Intensive Care Society Adult Patient Database. SETTING:
      Twenty-four intensive care units (ICU) across Australia. PATIENTS AND
      PARTICIPANTS: A cohort of 66,184 adult ICU admissions for >or=24 hours from
      January 1, 2000, to December 31, 2005. INTERVENTIONS: None. MEASUREMENTS AND MAIN
      RESULTS: Highest and lowest BG values within 24 hours of ICU admission, standard
      demographic, clinical, and physiologic data, and hospital mortality. Medical,
      mechanically ventilated surgical, cardiac surgical, and septic subgroups were
      evaluated. Average BG was evaluated as a continuous variable and by quartiles
      (low [<5.6 mmol/L], near normal [5.6-8.69 mmol/L], high [8.69-11.79 mmol/L], and
      highest [>11.79 mmol/L]). There were 132,368 BG values, with a mean (95%
      confidence intervals) value 8.69 mmol/L (8.66-8.73). There was no trend in BG for
      the entire cohort (p = 0.66) over the study period; yet, BG increased after 2002
      (0.17 mmol/L, p < 0.0001). The mechanically ventilated surgical and cardiac
      surgical subgroups had decreasing trends in BG (p < 0.001), whereas the septic
      subgroup had an increasing BG trend (p < 0.001). BG in the low, high, and highest
      quartiles, compared with the near-normal quartile, were consistently associated
      with higher hospital mortality in crude (odds ratio 1.31, 1.58, and 2.00) and
      multivariable analysis (odds ratio 1.29, 1.07, and 1.10), respectively. This
      association was similarly shown for the mechanically ventilated surgical and
      cardiac surgical subgroups. CONCLUSIONS: In a large cohort of ICU patients from
      Australia, there was no significant change in early glycemic control from 2000 to
      2005. There were differences in selected subgroups. Average BG decreased in
      surgical subgroups, whereas it increased in septic patients. Both high and early
      low BG values were independently associated with hospital mortality.

PMID- 19114916
TI  - PIRO score for community-acquired pneumonia: a new prediction rule for assessment
      of severity in intensive care unit patients with community-acquired pneumonia.
AB  - OBJECTIVE: To develop a severity assessment tool to predict mortality in
      community-acquired pneumonia (CAP) patients in intensive care unit (ICU),
      comparing its performance with Acute Physiology and Chronic Health Evaluation
      (APACHE) II score and American Thoracic Society/Infectious Disease Society of
      America (ATS/IDSA) criteria as a prognostic index in CAP patients requiring ICU
      admission. DESIGN: Secondary analysis of prospective observational cohort study.
      SETTING: Thirty-three ICUs. PATIENTS: Five hundred and twenty-nine adult patients
      with CAP requiring ICU admission. MEASUREMENTS AND MAIN RESULTS: A severity
      assessment score was developed based on the PIRO (predisposition, insult,
      response, and organ dysfunction) concept including the presence of the following
      variables: Comorbidities (chronic obstructive pulmonary disease,
      immunocompromise); age >70 years; multilobar opacities in chest radiograph;
      shock, severe hypoxemia; acute renal failure; bacteremia and acute respiratory
      distress syndrome. PIRO score was obtained at ICU within 24 hours from admission,
      and one point was given for each present feature (range, 0-8 points). The mean
      PIRO score was significantly higher in nonsurvivors than in survivors (4.6 +/-
      1.2 vs. 2.3 +/- 1.4). Considering the observed mortality for each PIRO score, the
      patients were stratified in four levels of risk: a) Low, 0-2 points; b) Mild, 3
      points; c) high, 4 points; and d) Very high, 5-8 points. Mild-risk (hazard ratio
      [HR] 1.8; 95% confidence interval [CI] 1.1-2.9; p < 0.05), high-risk (HR 3.1; 95%
      CI = 2.0-4.7; p < 0.001), and very high risk levels (HR 6.3; 95% CI = 4.2-9.4; p
      < 0.001) were significantly associated with higher risk of death in Cox
      proportional hazards regression analysis. Furthermore, analysis of variance
      showed that higher levels of PIRO score were significantly associated with higher
      mortality (p < 0.001), prolonged length of stay in the ICU (p < 0.001), and days
      of mechanical ventilation (p < 0.001). Receiver operating characteristic curves
      showed that PIRO score (area under the curve [AUC] = 0.88) performed better than
      APACHE II (AUC = 0.75, p < 0.001) and ATS/IDSA criteria (AUC = 0.80, p < 0.001)
      to predict 28-day mortality. CONCLUSIONS: The PIRO score performed well as 28-day
      mortality prediction tool in CAP patients requiring ICU admission with a better
      performance than APACHE II and ATS/IDSA criteria in this subset of patients.
      Furthermore, PIRO score also is associated with increased healthcare resource
      utilization in CAP patients admitted in the ICU.

PMID- 19114917
TI  - Acute left ventricular dilatation and shock-induced myocardial dysfunction.
AB  - OBJECTIVE: Whether cardiac ventricles can acutely dilate during septic myocardial
      dysfunction. DESIGN: A prospective echocardiographic study was performed to
      assess changes of left ventricular dimensions over time in patients with septic
      shock. SETTINGS: A 20-bed surgical intensive care unit of Pitie-Salpetriere
      university hospital in Paris. PATIENTS: Forty-five patients were studied over the
      first 10 days of septic shock. INTERVENTIONS: None. MEASUREMENTS AND MAIN
      RESULTS: Left ventricular end-diastolic area (LVEDA), fractional area change
      (FAC), velocity time integral of the aortic flow, echocardiographic indices of
      left ventricular relaxation, and cardiac troponin I (cTnI) were measured at day
      1, 2, 3, 4, 7, and 10. Three groups were defined: 29 patients without increased
      cTnI and cardiac impairment (group 1), eight patients with increased cTnI and
      left systolic ventricular dysfunction (group 2), and eight patients with
      increased cTnI and isolated impairment of left ventricular relaxation (group 3).
      At day 1, LVEDA was significantly higher in group 2 (13 +/- 3 cm/m, p < 0.05)
      compared with groups 1 (10 +/- 2 cm/m) and 3 (11 +/- 2 cm/m). LVEDA did not
      change in groups 1 and 3. In group 2, LVEDA and FAC returned within 10 days to
      values observed in groups 1 and 2. A significant correlation was found between
      aortic velocity time integral and LVDEA (r =.78, p = 0.022) and FAC (r =.89, p =
      0.003) only in group 2. CONCLUSIONS: Acute and reversible left ventricular
      dilation accompanies septic shock-induced systolic left ventricular dysfunction.
      When septic myocardial abnormalities are limited to reversible impairment of left
      ventricular relaxation, left ventricular dimensions remain unchanged.

PMID- 19114920
TI  - Extracorporeal cell therapy with granulocytes in a pig model of Gram-positive
      sepsis.
AB  - OBJECTIVES: Granulocyte transfusions have been used to treat immune cell
      dysfunction in sepsis. As granulocyte transfusions can trigger tissue injury via
      local effects of neutrophils, we hypothesized that extracorporeal treatment of
      plasma using granulocytes would prove beneficial while having less side effects.
      DESIGN: Prospective controlled three-armed animal study. SETTING: Research
      laboratory. SUBJECTS: Twenty-one female immature pigs (7.5-12 kg, 7-9 weeks old).
      INTERVENTIONS: Three groups of spontaneously breathing, sedated pigs (n = 7 each)
      received an intravenous lethal dose of live Staphylococcus aureus over 1 hour.
      Although group I had no specific treatment (control), group II and III were
      subsequently treated for 4 hours with an extracorporeal device containing either
      no cells (sham control, group II) or human cell line-derived granulocytic cells
      (group III). Survival time and physiologic, biochemical, and hematologic
      parameters were monitored for 7 days. MEASUREMENTS AND MAIN RESULTS: All animals
      of group I died during the observation time (mean survival time: 70 hours). In
      group II, two of seven and in group III, six of seven animals survived the
      observation time (mean survival: 75 and 168 hours, respectively). Survival
      differences were significant between group I and III (p < 0.001) and between
      group II and III (p < 0.05) but not between group I and II (p = 0.43).
      Furthermore, group differences in bacterial blood concentrations, differential
      blood count, blood gases, lactate, and interleukins were observed. The
      extracorporeal cell treatment was well tolerated by the animals. CONCLUSIONS:
      Extracorporeal therapy with granulocytic cells significantly improved survival in
      a pig model of sepsis. Further studies with this approach are encouraged.

PMID- 19114919
TI  - Modulation of nuclear factor-kappaB improves cardiac dysfunction associated with
      cardiopulmonary bypass and deep hypothermic circulatory arrest.
AB  - OBJECTIVE: The hypothesis is that partial nuclear factor-kappaB (NF-kappaB)
      inhibition can alleviate cardiopulmonary dysfunction associated with ischemia and
      reperfusion injury following cardiopulmonary bypass and deep hypothermic
      circulatory arrest (CPB/DHCA) in a pediatric model. DESIGN: Animal case study.
      SUBJECTS: Two-week-old piglets (5-7 kg). INTERVENTIONS: Piglets received 100
      microg/kg of SN50, a peptide inhibitor of NF-kappaB translocation and activation,
      1 hour before CPB. The control group received saline. Animals were cooled to 18
      degrees C with CPB, the piglets were in DHCA for 120 minutes, and the piglets
      were then rewarmed on CPB to 38 degrees C and maintained for 120 minutes after
      CPB/DHCA. MEASUREMENTS: Sonomicrometry and pressure catheters collected
      hemodynamic data. Transmural left and right ventricular tissues were obtained at
      the terminal time point for determination of NF-kappaB activity by enzyme-linked
      immunosorbent assay. Data are expressed as mean +/- sd. MAIN POINTS: Oxygen
      delivery was maintained at 76 +/- 13 mL/min at baseline and 75 +/- 5 mL/min at
      120 minutes after CPB/DHCA (p = 0.75) in SN50-treated animals vs. 99 +/- 26
      mL/min at baseline and 63 +/- 20 mL/min at 120 minutes in the untreated group (p
      = 0.0001). Pulmonary vascular resistance (dynes.sec.cm) increased from 124 +/- 59
      at baseline to 369 +/- 104 at 120 minutes in the untreated piglets (p = 0.001)
      compared with SN50-treated animals (100 +/- 24 at baseline and 169 +/- 88 at 120
      minutes, p = 0.1). NF-kappaB activity was reduced by 74% in left ventricles of
      SN50-treated compared with SN50-untreated animals (p < 0.001). Plasma endothelin
      1 (pg/mL), an important vasoconstrictor regulated by NF-kappaB, increased from
      2.1 +/- 0.4 to 14.2 +/- 5.7 in untreated animals (p = 0.004) but was elevated to
      only 4.5 +/- 2 with SN50 treatment (p = 0.005). CONCLUSIONS: Improvement of
      cardiopulmonary function after ischemia/reperfusion was associated with the
      reduction of NF-kappaB activity in piglet hearts. Maintenance of systemic oxygen
      delivery and alleviation of pulmonary hypertension after CPB/DHCA in piglets
      administered SN50, possibly through a reduction of circulating endothelin-1,
      suggest that selective inhibition of NF-kappaB activity may reduce ischemia and
      reperfusion injury after pediatric cardiac surgery.

PMID- 19114923
TI  - Two teenagers with sepsis and pneumonia.

PMID- 19114918
TI  - Therapeutic hypothermia preserves antioxidant defenses after severe traumatic
      brain injury in infants and children.
AB  - OBJECTIVE: Oxidative stress contributes to secondary damage after traumatic brain
      injury (TBI). Hypothermia decreases endogenous antioxidant consumption and lipid
      peroxidation after experimental cerebral injury. Our objective was to determine
      the effect of therapeutic hypothermia on oxidative damage after severe TBI in
      infants and children randomized to moderate hypothermia vs. normothermia. DESIGN:
      Prospective randomized controlled study. SETTING: Pediatric intensive care unit
      of Pittsburgh Children's Hospital. PATIENTS: The study included 28 patients.
      MEASUREMENTS AND MAIN RESULTS: We compared the effects of hypothermia (32 degrees
      C-33 degrees C) vs. normothermia in patients treated in a single center involved
      in a multicentered randomized controlled trial of hypothermia in severe pediatric
      TBI (Glasgow Coma Scale score <or=8). The patients randomized to hypothermia (n =
      13) were cooled to target temperature within approximately 6 to 24 hours for 48
      hours and then rewarmed. Antioxidant status was assessed by measurements of total
      antioxidant reserve and glutathione. Protein oxidation and lipid peroxidation
      were assessed by measurements of protein thiols and F2-isoprostane, respectively,
      in ventricular cerebrospinal fluid (CSF) samples (n = 76) obtained on day 1-3
      after injury. The association between Glasgow Coma Scale score, age, gender,
      treatment, temperature, time after injury, and CSF antioxidant reserve,
      glutathione, protein-thiol, F2-isoprostane levels were assessed by bivariate and
      multiple regression models. Demographic and clinical characteristics were similar
      between the two treatment groups. Mechanism of injury included both accidental
      injury and nonaccidental injury. Multiple regression models revealed preservation
      of CSF antioxidant reserve by hypothermia (p = 0.001). Similarly, a multiple
      regression model showed that glutathione levels were inversely associated with
      patient temperature at the time of sampling (p = 0.002). F2-isoprostane levels
      peaked on day 1 after injury and were progressively decreased thereafter.
      Although F2-isoprostane levels were approximately three-fold lower in patients
      randomized to hypothermia vs. normothermia, this difference was not statistically
      significant. CONCLUSION: To our knowledge, this is the first study demonstrating
      that hypothermia attenuates oxidative stress after severe TBI in infants and
      children. Our data also support the concept that CSF represents a valuable tool
      for monitoring treatment effects on oxidative stress after TBI.

PMID- 19114924
TI  - The intercontinental schizophrenia outpatient health outcomes (ic-soho) study:
      baseline clinical and functional characteristics and antipsychotic use patterns
      in the central and eastern europe (cee) region.
AB  - OBJECTIVE: To describe the baseline findings of the Intercontinental
      Schizophrenia Outpatient Health Outcomes (IC-SOHO) study in the Central and
      Eastern European sub-region (CEE-SOHO). METHOD: The IC-SOHO study is an ongoing
      prospective, three-year, non-interventional observational study of schizophrenia
      treatment, clinical characteristics and mental health services utilization in
      eight Central and Eastern European countries. The study population consists of
      non-hospitalized patients who had initiated treatment with or changed to a new
      antipsychotic. RESULTS: The baseline findings of the IC-SOHO study (CEE-SOHO
      Subset) appear to reflect clinical practice in Russia, Poland, Czech Republic,
      Slovakia, Slovenia, Hungary, Romania and Lithuania (N=2,247). Overall, the
      patients were moderately to markedly ill and either overweight or obese (61.1%)
      when they entered the study. Functionally, the majority of patients was not
      involved in a relationship, could not care for themselves and was unemployed.
      Substance and alcohol dependency/abuse was not a problem in this study
      population. At baseline, half of the patients were treated with the newer
      atypical antipsychotics; and anxiolytics/hypnotics were the most commonly
      prescribed concomitant medication. Sexual side effects were most frequently
      reported among the surveyed adverse events. Overall patient compliance/ adherence
      to medication was good. CONCLUSION: The baseline IC-SOHO data highlighted various
      clinical and functional characteristics and antipsychotic use patterns in a group
      of outpatients with schizophrenia in a naturalistic setting. Once completed, the
      IC-SOHO study will add further to this knowledge base.

PMID- 19114925
TI  - Suicides in croatia 1993-2001: regional differences.
AB  - OBJECTIVE: With regard to historical, economical, cultural, climate and probably
      genetic diversity of the Republic of Croatia, it is to be expected to find
      significant regional differences in suicide rates. The aim of this paper is to
      describe the specific regional characteristics of suicide rates in Croatia and
      compare it with that in neighbour countries like Slovenia, Hungary and Italy.
      METHOD: Using official suicide statistics, this study examined suicide rate in
      Croatia over a 8-years span (1993-2001) as the function of age, gender,
      employment and marital status and geographical regions. RESULTS: Our results
      demonstrated: a). higher suicide rate in the Continental part (21.96) in
      comparison with the Mediterranean part (15.42) of Croatia as well as lower
      suicide rate in the South (10.91) compared to the North (22.28) of Mediterranean
      Croatia; b). higher suicide male/female ratio in the Continental (3.49) than in
      the Mediterranean (2.36) Croatia as well as in the North (2.77) than in the South
      (1.94) of Mediterranean Croatia; c). bigger percentage of suicide in younger age
      (15-24 years) in the South (11.58%) than in the North (3.97%) of Mediterranean
      Croatia; d). lowest rate of homicide and lowest divorce rate were found in the
      South of Mediterranean Croatia with lowest suicide rates. CONCLUSION: This study
      showed significant regional differences in suicide rates accros the Republic of
      Croatia. With its south Mediterranean part, Croatia share the same low rate with
      Mediterranean neighbour Italy, while with its west-north continental part Croatia
      with high suicide rate is similar to its neighbours Slovenia and Hungary.

PMID- 19114926
TI  - Suicidal ideation and medical profession: from medical students to hospital
      physicians.
AB  - OBJECTIVE: With regard to an increased risk of suicide among physicians, the
      prevalence and predictors of suicidal ideation among medical students have
      attracted increased attention in recent years. The aim of this study was to
      investigate the level and characteristics of suicidal ideation in medical
      students and hospital physicians of School of Medicine, University of Mostar.
      SUBJECTS AND METHOD: Suicidal ideation was assessed in 200 students: 45 students
      of the first year, 36 students of the second year, 44 students of the third year,
      28 students of the fourth year, 25 students of the fifth year and 22 students of
      the sixth year and 90 hospital physicians. RESULTS: Some form of the actual
      suicidality was found in 9.16% of medical students: 4.4% of students of the first
      year, 8.4% of students of the second year, 9.1% of students of third year, 3.6%
      of students of the fourth year, 13.6% of the sixth year as well as in 2.2% of the
      hospital physicians. CONCLUSIONS: The level of suicidal ideation among medical
      students is warning and should initiate preventive interventions.

PMID- 19114927
TI  - Suicides of the hospitalized chronic shizophrenic patients in the period from
      1972 to 2002.
AB  - The paper deals with the data on suicides of the hospitalised chronic
      schizophrenic patients in the pre-war, war and post-war time, i.e. the period
      from 1972 to 2002. The subjects are the schizophrenic patients from the
      Psychiatric hospital of Domanovici who were moved at the beginning of war to the
      premises of the Clinical hospital of Mostar. Special attention in the analysis
      has been paid to the war year of 1992, when a high rate of suicides was
      registered among the hospitalised schizophrenic patients, the data showing their
      number, gender, age, diagnosis, duration of illness, hospitalisation as well as
      earlier attempts of suicide or suicides in their families. The results of the
      research show the increase in the number of suicides in the period of the most
      terrible war events, caused by their displacement, inadequate accommodation, lack
      of food and medicines. This research is epidemiological, retrospective,
      descriptive and analytic.

PMID- 19114928
TI  - Comorbidity of the posttraumatic stress disorder and the depression in ex
      prisoners of war.
AB  - The interest in investigating the war related posttraumatic stress disorder
      (PTSD) has increased both in the world and in Bosnia and Herzegovina (BiH) over
      the last decades. Extensive literature indicates the association between PTSD and
      other psychiatric disorders. The most frequent disorders associated with PTSD
      are: depression, anxiety disorder and the abuse of psychoactive substances and
      alcohol. Some studies show that the depression is the most frequent disorder
      which follows PTSD. We studied the comorbidity of PTSD and depression in ex-war
      prisoners and in war veterans five years after the end of the war in Bosnia and
      Herzegovina. The study sample was divided into two groups. The first group is
      composed of 100 ex-prisoners of war, and the second one consists of 60 war
      veterans who were not confined in camps. The questionnaires under the criteria
      DSM IV were used to diagnose PTSD and depression. All the respondents were males
      and all of them were in good health before the war. The results obtained show a
      statistically significant higher representation of PTSD and depression in the
      prisoners of war as compared with the war veterans at the level of p<0.05. We
      also found a significant association of PTSD and depression, both in the
      prisoners of war and in the war veterans, however, there is no statistically
      signifficant difference between the studied groups.

PMID- 19114929
TI  - Suicide in schizophrenia: risk factors, therapy and preventive strategies.
AB  - Among patients with schizophrenia and schizoaffective disorders, as many as 40%
      attempt suicide at some time in their lives, and approximately 10% die from
      suicide. The emotional, economic, and societal costs of suicidal behavior are
      enormous, making identification of ways to predict and reduce this risk a high
      priority public health issue. The gratest risk for suicidal behavior is while in
      the hospital or within the 6 months subsequent to discharge from the hospital. In
      schizophrenia, individuals with suicidal behavior are hospitalized significantly
      more frequently than non-suicidal individuals. Therefore clinicians must increase
      their assessment of suicidal behavior. Methodical assessment of suicidal ideation
      and aggressive treatment with psychological, social, and pharmacologic approaches
      are vital aspects of patient management. Determination of reliable predictors of
      suicide risk would not only help reduce the mortality associated with suicide
      attempts but could also permit more rational allocations of resources for
      treatment and should reduce the emotional and economic burden of this behavior on
      families and society. In this paper was considering risk factors for suicide in
      schizophrenic patients and the implications for preventive strategies.

PMID- 19114930
TI  - [Systemisch-integrative diagnostik in der psychosomatik.].
AB  - After a short description of the professional context and the work of the author
      he describes five technics of a psychosomatic diagnostic in some cases developed
      by him: reconstruction of familiar relation patterns with the genogram,
      development of illness supporting relation patterns, working with the creation of
      boarders between men und their life contexts, systemic integrative sculpturing,
      working with the role management rhombus.

PMID- 19114931
TI  - [Indikationsfragen zur psychotherapie bei psychosomatischen patientinnen.].
AB  - The diagnostic process of psychosomatic patients finally arriving at an
      indication for psychotherapy is an important point of reference in the present
      discussion concerning the introduction of special clinics for psychosomatic
      patients in Austria: equippment of such clinics and standards for the personnel
      has to relate to the needs of these patients. The Etiology of psychosomatic
      disturbances includes psychological influences, which, via
      psychoneuroendocrinolgical mechanisms interact with somatic factors, and
      individual coping styles, shaped by the social environment and gender-related
      factors. The initial interview, besides physical complaints, has to assess the
      patient's reality sense, the affective competence, the cognitive competence, the
      nature and quality of relations with important others, the subjective illness
      theories and the motivation for psychotherapy. The therapeutic method/setting
      finally choosen has to offer a scientifically based concept of psychosomatic
      disturbances, according to the different operationalisations of Psychosomatic.

PMID- 19114932
TI  - [Psychosomatische behandlung chronischer schmerzpatientinnen.].
AB  - At present, pain is conceptualized as an unpleasant sensory and emotional
      experience, including biological and psychosocial components. Thus, the classical
      distinction of somatogenic and psychogenic pain is heuristically no longer
      useful. For the understanding of the development and chronification of pain, the
      identification of predisposing, precipitating and perpetuating factors are of
      value. Biological, psychological and sociocultural aspects should be considerd
      for the diagnostic procedure and the treatment of pain patients. As this, a
      multidisciplinary pain management can be conceptualized as a stepwise approach of
      increasing treatment complexity, including different health professions
      (physician, psychologist/psychotherapist, nurses, physiotherapist, occupational
      therapist, social worker) and various settings (consultation-liaison(C/L)
      services, outpatient pain clinics, day hospitals, inpatient wards). The efficacy
      of an multidisciplinary pain treatment has been clearly demonstrated by numerous
      studies during the last years.

PMID- 19114933
TI  - [Angewandte psychosomatik am beispiel des psychosomatischen konsiliar-/liaison
      dienstes.].
AB  - The discussion around the integration of a psycho-social approach in medicine
      concerning "patient-centred medical care" has gained increasing importance in the
      last few years especially at medical conferences and in text books. This
      importance has not been mirrored, however, in the daily life of hospital
      patients. A well-proven model of co-operation between psychiatric/ psychosomatic
      departments and other medical departments are the so-called consiliar/ liaison
      services. These have been developed in psychiatry and represent an especially
      close type of co-operation going beyond the classical and generally known
      counselling model. The following article gives a general overview of this form of
      co-operation with special consideration given to the situation in Austria.
      Questions concerning fields of duty, needs and the efficiency of C/L services are
      elaborated in the selection of areas of special emphasis. As examples, results of
      a few empirical studies will be illustrated which in many respects give
      encouragement to increasingly implement this form of applied psychsomatics in our
      hospitals.

PMID- 19114934
TI  - [DER ANFANG IST DIE HALFTE DES GANZEN (PLATON) Konzept der psychosomatischen
      Abteilung an der Landes-Nervenklinik Wagner-Jauregg.].
AB  - The psychosomatic department is the first institution of this kind in Upper
      Austria. Our intention is to present a competence center for the treatment of
      mind and body. In interdisciplinary co-operation we want to create a field of
      learning based on the bio-psycho-social model of disease, which provides a
      possibility for patients to improve their quality of life and therefore helps to
      soothe the symptoms of illness or to avoid its worsening.

PMID- 19114935
TI  - Editorial: SUICIDE THROUGH THE EYES OF THE RIDDLER.

PMID- 19114936
TI  - Slovenian suicides as seen through time and space.
AB  - The objective of this review is to provide general facts and data regarding
      Slovenian suicides. Recent data shows Slovenia having a suicide rate of around
      30, which places it among the highest rates in the world. The review examined
      Slovenian suicides both apart from and in comparison to world data and trends.
      Historical suicide statistics are dealt with, including an evaluation of data
      collected during the Yugoslavian years in contrast with data collected following
      the independence of Slovenia in 1991. The discussion includes an assessment of
      suicide rates throughout Europe and possible explanations for various trends in
      these rates, including potential economic, genetic, and alcohol-related causes.
      Furthermore the variations in suicide rates throughout Slovenian municipalities
      are discussed. Both unique aspects of Slovenian suicide (such as a high
      proportion of hangings) and commonalities with world data are reviewed. Suicide
      in Slovenia is a considerable public mental health problem and in order to
      prevent it, we must first thoroughly understand its characteristics in time and
      space.

PMID- 19114937
TI  - The effects of fluoxetine on cognitive functions in animal model of Alzheimer's
      disease.
AB  - Cognitive impairment is the hallmark of progressive neurodegenerative process
      observed in Alzheimer's disease (AD). Acetylcholine (Ach) deficiency is
      considered to be one of major factors underlying cognitive dysfunction in AD.
      Several lines of evidence suggest that sigma receptor ligands can elevate Ach
      extracellular levels in prefrontal cortex rat brain. Since all selective
      serotonin reuptake inhibitors (SSRIs) show affinity for sigma receptors, it has
      been assumed that fluoxetine could improve cognition in AD. The aim of study was
      to investigate the effects of fluoxetine on learning and memory processes in
      experimental model of AD in rats. Experiments were carried out on adult male
      Wistar rats divided into three major groups: intact control, sham-operated and
      nucleus basalis-lesioned rats. Bilateral electrolytic lesions of nucleus basalis
      Meynert (NBM) (experimental model of AD) were made by 1 mA direct current passed
      through unipolar electrode for 30 sec. The behavioural test (active avoidance)
      was performed after recovery period of 10 days from the lesion. The effects of
      several doses of fluoxetine (3, 5 and 10 mg/kg) on these processes were
      investigated after 7 days of administration. The results showed that lesion of
      NBM in rats markedly impaired learning and memory processes compared with
      controls (intact and sham). Fluoxetine in 5 mg/kg daily doses significantly
      improved (p<0.05) these processes in lesioned animals. These findings suggest
      that fluoxetine could be useful as symptomatic therapy in the treatment of AD.

PMID- 19114938
TI  - The frontal lobe hypothesis: impairment of executive cognitive functions in
      chronic alcohol in-patients.
AB  - OBJECTIVES: Previous research has found that recently detoxicated alcoholics show
      impairments in executive cognitive functions, supporting the frontal lobe
      hypothesis. The study is testing the hypothesis that participants with alcohol
      dependence syndrome will show impairments in cognitive flexibility, planning and
      problem solving, ability to learn and information processing speed. METHOD: The
      performance of twenty-eight participants with alcohol dependence syndrome was
      compared to controls using three neuropsychological tests (Stroop colour and word
      test, Tower of London, Wisconsin card sorting test) sensitive to executive
      cognitive functions. RESULTS: The alcoholics were found to be impaired in almost
      every executive cognitive function measured. Compared to controls, they showed
      impairments in cognitive flexibility, information processing speed, planning and
      problem solving. No significant differences were found regarding ability to
      learn. CONCLUSION: Present findings confirm the frontal lobe hypothesis and are
      consistent with the results of previous studies that revealed significantly
      impaired executive cognitive functions in recently detoxicated alcoholics.

PMID- 19114939
TI  - Some aspects of self-destructive behavior in forensic psychiatric inpatients.
AB  - In this study authors have analysed a group of patients (N=65) that were treated
      at the Department of Forensic Psychiatry, Psychiatric Hospital Rab, during the
      period of 1998-2000. Detailed analysis of all anamnestic and hetero-anamnestic
      data as well as the observations during the treatment separated few significant
      patterns of self-destructive behaviour of various intensity and different
      possible consequences. The results showed out that within the first group of
      patients with self-destructive behaviour was noticed a significant increased
      number of younger age patients who were diagnosed with personality disorder
      especially borderline and antisocial type. Additionally facing difficulties with
      alcohol abuse and drug addiction. In a second group there were older patients
      with serious attempt of suicide dominantly diagnosed with endogenous psychosis,
      especially schizophrenia.

PMID- 19114940
TI  - [Fragebogen zur erfassung der eltern-kind-bindung im schulalter (ekb-s).].
AB  - The german version of the Maternal/Paternal Fetal Attachment Scale The german
      validation of the Parent-child-Reunion Inventory (Marcus, 1997), which assesses
      the parent-child-relationship at the early school-age, is reported. The
      questionnaire is economically and statistically sufficiently tested. The EKB-S
      consists of 20 items, which can be answered within 10 minutes. The sample size
      was 121. The assessed attachment categories are the same M. Ainsworth (1978)
      reported.

PMID- 19114941
TI  - Impact of war traumatic events on the socio-demographic characteristics of the
      civilian population in bosnia and herzegovina.
AB  - AIM: The aim of the present contribution is to present the socio-demographic
      characteristics of the torture survivors and specific life changes caused by the
      torture, and to create real assumptions for adequate socio-medical treatment.
      SUBJECTS AND METHODS: The present research was carried out in the Psychiatric
      clinic in Sarajevo with patients who were victims of torture during the
      aggression on Bosnia and Herzegovina, who were treated after the aggression for
      psychological and physical disorders. Socio-demographic data were collected by
      applying the specially constructed General Questionnaire consisting of 28
      questions, prior to the psychiatric interview. After that a statistical analysis
      of the data collected was carried out.

PMID- 19114942
TI  - Specific differences in trauma related symptoms between the refugees survivors of
      torture and refugees of war.
AB  - AIM: The aim of this study was to determine specific differences in trauma
      related symptoms in a group of subjects who were survivors of torture and
      displacement compared with a group of subjects who survived displacement as a
      consequence of state sponsored violence in Bosnia and Herzegovina. SUBJECTS: The
      subjects were divided in two groups of 50 adult survivors; one group comprising
      of 50 survivors of displacement and torture, the other group of 50 survivors of
      displacement who did not experience torture. The age range of the subjects was
      between 20 and 60. The groups were homogenous according to all other criteria.
      The exclusion criteria were prior psychiatric history and the experience of a
      loss of secondary family (spouse or child). METHODS: All subjects were assessed
      using the standardized multidimensional instrument for symptom assessment, SCL 90
      R (L.R.Derogatis, 1986). Mississippi Questionnaire, (Keane et al. 1988), was used
      for assessment of symptoms of PTSD. Sociodemographic questionnaire designed by
      the authors was used for registering of the sociodemographic characteristics of
      the subjects. RESULTS: The results of our study show a statistically significant
      difference in trauma related symptoms between a group of subjects who were
      refugees with the experience of torture and a group of subjects who were refugees
      only. The symptoms of PTSD are increased in survivors of torture to a degree that
      is statistically significant compared with the presence of PTSD symptoms in a
      group of refugees. Anxiety, depression, somatization, obsessive-compulsive
      symptoms, phobic symptoms, hostility, interpersonal sensitivity, paranoid and
      psychotic symptoms are present to a statistically higher degree in a group of
      refugees survivors of torture than in the group of refugees. There is also a
      statistically significant difference between the groups in socio-economic status
      in the period after the war. Refugees survivors of torture have significantly
      worse socio-economic situation, probably due to impairment in social functioning
      in these subjects.

PMID- 19114943
TI  - Specific differences in trauma related symptoms between war veterans and the
      civilian population.
AB  - AIM: The aim of this study was to determine specific differences in trauma
      related symptoms between the civilians who survived the trauma of war and
      veterans of war who have had the experience of combat stress. METHODS: The study
      involved two groups of subjects, with 50 male subjects in the age range between
      20 and 50 in each group who had no psychiatric history prior to traumatization.
      All subjects were assessed for psychopathological symptoms using the
      multidimensional instrument for symptom assessment SCL 90-R (L.R. Derogatis
      1986.). This instrument contains 90 articles divided in 9 subscales. PTSP
      symptoms were assessed with Mississippi Questionnaire designed by Keane et al
      1988, and containing 35 articles. Sociodemographic characteristics were
      registered by the use of a special questionnaire designed by the authors.
      CONCLUSIONS: Our results indicate a statistically significant difference in the
      presence of symptoms between the two groups. Both PTSP and other related symptoms
      were present in statistically significant higher degree in the group of war
      veterans than in the group of civilian survivor of war traumas. There is also a
      statistically significant difference in socio-economic status in the period after
      the war between the two groups. This difference is at a disadvantage of the group
      of war veterans who are fairing significantly worse. This is probably due to the
      consequences of traumatization as well to secondary traumatization, absence of
      expected reward for their effort and impairment in social functioning in the
      group of war veterans.

PMID- 19114944
TI  - Quality of life assessment as the treatment outcome evaluation of war torture
      survivors according to gender.
AB  - OBJECTIVE: The objective is the evaluation of treatment outcome difference
      between men and women through measuring quality of life persons who experienced
      war torture in Bosnia and Herzegovina. METHOD: The research is analytical
      descriptive and retrospective. It was conducted at two samples which were
      homogeneous according to gender. All persons included in the research regarding
      torture consequences have received comprehensive psychosocial rehabilitation at
      the Association for Rehabilitation of Torture Victims-Centre for Torture Victims
      in Sarajevo, Bosnia and Herzegovina. MANSA (Manchester Short Assessment of
      Quality of Life) questionnaire have been applied as instrument of research.
      RESULTS: The results indicates that women who experienced war torture, after
      completition of psychosocial rehabilitation, have bit better quality of life in
      post war conditions comparing to men. CONCLUSION: Generally, the quality of life
      results, both men and women war torture survivors are representing the evaluation
      of treatment outcome, justifying fully purpose of this treatment type.

PMID- 19114945
TI  - Specific characteristics of the group psychotherapy of neurotic patients who
      survived war traumatization.
AB  - The paper will show specific characteristics of the psychodynamic group
      psychotherapy in the small group of patients. Primary indications for the
      psychotherapy were expressed neurotic disorders. All patients have survived war
      traumatization, and some survived trauma of being refugee and separation from the
      other family members. Therapeutic atmosphere suitable for exploration of the
      neurotic conflicts has been created. At the same time traumatic contents that
      were asking for cognitive and emotional elaboration were emerging from time to
      time. We have supported that with the continuous effort to bring the patient
      closer to the identified clear connection between neurotic symptoms, early
      infantile traumatization and stronger sensibility to the experience of the war
      traumatization related to it. By better awareness and understanding the patient
      has been increasing the ability to deal with the neurotic conflict as well as
      with the psychological injuries created during the war traumatization.

PMID- 19114946
TI  - Observational postmarketing study on efficacy and safety of novel generic
      risperidone risset(r) in patients with acute or chronic schizophrenic or other
      related psychosis.
AB  - Objective. The aim of this study was to establish the effectiveness and safety of
      risperidone (Risset(R) - PLIVA) in patients with acute or chronic schizophrenic
      or other related psychosis. Study was designed as postmarketing, 4-week, open
      label, flexible-dose observational study. Subjects and Methods. 30 patients, both
      genders, aged 18-70 years, with diagnosed various types of schizophrenic
      psychosis were enrolled in the study as outpatient and inpatient setting. The
      patients had to have a total score >/=40 on Positive and Negative scale - two
      parts of the Positive and Negative Syndrome Scale (PANSS), and to be able to
      discontinue current antipsychotic and antiparkinsonian medications. The primary
      efficacy parameter was the percent of score difference between baseline and week
      4 of therapy on two above-mentioned PANSS subscales. The difference was
      considered as significant improvement if decrease from the baseline was 20% or
      more. The safety of risperidone was evaluated on the basis of reported adverse
      events. Results. All 30 enrolled patients completed the study. After the 4 weeks
      of treatment, 23/30 patients (76.67%) had clinically significant improvement of
      20% or more decreased total PANSS score (Positive and Negative subscale). In 4/30
      patients (13.33%) clinical improvement was also reported with <20% decreased
      total PANSS score. No serious adverse event was observed. Conclusions. Overall,
      collected data indicate that in this specific population (70% patients were
      resistant to previous anti-psychotic therapy), Risset(R) has shown very good
      effectiveness and safety.

PMID- 19114947
TI  - Some historical remarks and current state of mental health services in bosnia and
      herzegovina.
AB  - In this paper we have presented historical overview of development of psychiatric
      services in Bosnia and Herzegovina. Special attention was given to the recent war
      destruction (l992-l995), as well as to the reconstruction and reform of mental
      health services within a frame of newly introduced mental health strategy.

PMID- 19114948
TI  - Letter to the editor: novel evidence on bisphosphonate related osteochemonecrosis
      of the jaws suggests tooth extractions and overdentures as risk factors.

PMID- 19114949
TI  - Ancient schwannoma arising from mental nerve. A case report and review.
AB  - Schwannoma is an intraoral rare, benign neoplasm derived from the nerve sheath of
      peripheral nerves. "Ancient schwannoma" shows histopathological features, such as
      degenerative changes and atypical nuclei, and may easily be confused with
      malignant neoplasms. Ancient schwannoma of the head and neck region is relatively
      uncommon and very few cases had been reported in the oral cavity. We present a
      case of ancient schwannoma arising from the mental nerve in a 19 year old male
      which was of eight months duration. Examination revealed a 30 x 25 mm firm,
      strawberry-like mass in the periapical region of the left lower first premolar,
      extending anteriorly to the canine and posteriorly to the first molar,
      obliterating the buccal vestibule, with an intact overlying mucosa.
      Ultrasonography showed that the tumor was closely associated with the mental
      nerve on the left side, suggestive of a peripheral neural sheath tumor. Complete
      excision of the lesion was done under local anesthesia, preserving the mental
      nerve. The histological picture was strongly suggestive of ancient schwannoma
      (Antoni A type). There was no evidence of recurrence 18 months after excision.
      The clinicopathological aspects of this special case are discussed, and the
      literature regarding this entity is reviewed.

PMID- 19114950
TI  - Rational use of antimicrobials in dentistry during pregnancy.
AB  - The use of medicines during pregnancy deserves special attention from dentists
      due to the potential risks to fetal development. The prescription of
      antimicrobial drugs during this period must be based not only on the etiology of
      the disease but also on the drug's effect on the embryo, which may be toxic,
      possibly leading to irreversible lesions. Interest in studies of the teratogenic
      effects of drugs increased in response to reports of the high incidence of
      phocomelia in patients treated with thalidomide. Although teratogenicity has long
      been known, pregnant women today are still exposed to this risk. The effects of
      drugs depend on the level of susceptibility of the fetus and on the period of
      exposure during pregnancy. In this context, and considering the paucity of
      studies on this subject in dentistry, the aim of this review was to offer an up
      to-date compilation of data on the antimicrobial drugs most frequently used
      during pregnancy and the effects of their use.

PMID- 19114951
TI  - Pharmacological interactions of vasoconstrictors.
AB  - This article is the first of a series on pharmacological interactions involving
      medicaments commonly prescribed and/or used in odontology: vasoconstrictors in
      local anaesthetics and anti-inflammatory and anti-microbial analgesics. The
      necessity for the odontologist to be aware of adverse reactions as a result of
      the pharmacological interactions is due to the increase in medicament consumption
      by the general population. There is a demographic change with greater life
      expectancy and patients have increased chronic health problems and therefore have
      increased medicament intake. The presence of adrenaline (epinephrine) and other
      vasoconstrictors in local odontological anaesthetics is beneficial in relation to
      the duration and depth of anaesthesia and reduces bleeding and systemic toxicity
      of the local anaesthetic. However, it might produce pharmacological interactions
      between the injected vasoconstrictors and the local anaesthetic and adrenergic
      medicament administered exogenically which the odontologist should be aware of,
      especially because of the risk of consequent adverse reactions. Therefore the
      importance of conducting a detailed clinical history of the general state of
      health and include all medicaments, legal as well as illegal, taken by the
      patient.

PMID- 19114952
TI  - Antibiotic prophylaxis to prevent local infection in Oral Surgery: use or abuse?
AB  - Antibiotics have a well-documented efficacy in the treatment of established
      infections and as prophylactic agents in medically compromised patients. However,
      the systematic administration of antibiotics to prevent local infections in fit
      patients is much more controversial. The aim of this paper is to reflect on the
      justification for prophylactic usage of antibiotics to prevent wound infection
      and to reason out the most appropriate antibiotic guidelines taking into account
      available scientific data and studies by other authors. Numerous clinical trials
      question the efficacy of antibiotics in preventing wound infection. While some
      studies establish that antibiotics reduce the incidence of postoperative
      infections, others compare their efficacy to that of placebo. Thus, scientific
      literature suggests that every oral surgical intervention is not tributary of
      systematic antibiotic prophylaxis to prevent local infections. Intrinsic surgical
      risk factors and the patient's individual circumstances must be taken into
      account. Even though the efficacy of other antibiotics cannot be ruled out due to
      our limited comprehension of the bacteriologic interrelations intervening in the
      pathogenesis of postextraction local infection, the amoxicillin-clavulanic acid
      combination theoretically covers the complete odontogenic bacterial spectrum in
      Spain. When the prophylactic use of antibiotics is indicated, this should be
      performed preoperatively, at high doses, and its extent should not exceed 24
      hours. Special attention should be paid to antiinfectious local measures that can
      minimize infection risk during the wound's healing period.

PMID- 19114953
TI  - The use of tricyclic antidepressants in the treatment of temporomandibular joint
      disorders: systematic review of the literature of the last 20 years.
AB  - Many therapies have been proposed for the management of temporomandibular
      disorders, including the use of different drugs. However, lack of knowledge about
      the mechanisms behind the pain associated with this pathology, and the fact that
      the studies carried out so far use highly disparate patient selection criteria,
      mean that results on the effectiveness of the different medications are
      inconclusive. This study makes a systematic review of the literature published on
      the use of tricyclic antidepressants for the treatment of temporomandibular
      disorders, using the SORT criteria (Strength of recommendation taxonomy) to
      consider the level of scientific evidence of the different studies. Following
      analysis of the articles, and in function of their scientific quality, a type B
      recommendation is given in favor of the use of tricyclic antidepressants for the
      treatment of temporomandibular disorders.

PMID- 19114954
TI  - Surgical treatment of temporomandibular joint ankylosis: follow-up of 15 cases
      and literature review.
AB  - INTRODUCTION: Ankylosis may be defined as the fusion of the articular surfaces
      with bony or fibrous tissue. The treatment of temporomandibular joint ankylosis
      poses a significant challenge because of the high incidence of recurrence.
      PURPOSE: To report 15 cases treated by either gap arthroplasty, or the articular
      reconstruction technique using costochondral grafts, coronoid process grafts or
      alloplastic condylar implants; evaluate the results of these surgeries and make a
      literature review. METHODS: The sample was obtained from the records of the
      Oswaldo Cruz University Hospital (HUOC-UPE) of patients submitted to ankylosis
      treatment by alloplastic or autogenous graft between March 2000 and October 2006.
      Pre-and post-operative assessment included a thorough history and physical
      examination to determine the cause of ankylosis, the maximal incisal opening,
      etiology and type of the ankylosis, recurrence rate and presence of facial nerve
      paralysis. RESULTS: The mean maximal incisal opening in the preoperative period
      was 8.71 + 6.97 mm and in the postoperative period it was 28.50 + 8.10 mm, the
      recurrence rate was 20% (n=3), and always occurred in ankylosis type IV.
      CONCLUSION: The articular reconstruction with alloplastic or autogenous grafts,
      or gap arthroplasty for the treatment of ankylosis is shown to be efficient in
      relation to the post-operative maximal incisal opening, recurrence and articular
      function.

PMID- 19114955
TI  - Chondrosarcoma of the temporomandibular joint. A case report and review of the
      literature.
AB  - Chondrosarcoma is a malignant tumor characterized by the formation of cartilage,
      but not bone, by tumor cells. Only 5% to 10% of chondrosarcomas occur in the head
      and neck, representing 0.1% of all head and neck neoplasms, with the larynx and
      the maxillo-nasal region being the most common sites. This report describes an
      unusual case of chondrosarcoma in a 54-year-old man who presented with pain and
      swelling in the left preauricular area. Computed tomography demonstrated a soft
      tissue mass in the left temporomandibular joint without causing erosion of the
      adjacent bony structures. The tumor was treated by excision in a single block
      with perilesional tissues, preserving the facial nerve. Histopathologic
      examination revealed chondrocytes with irregular nuclei with S-100
      immunocytochemical staining positive in 30% of the tumor. The diagnosis was a
      grade I chondrosarcoma. There was no evidence of disease at the 16-month follow
      up. The occurrence of chondrosarcoma in the temporomandibular joint (TMJ) is an
      exceptional event, with only 16 cases described. We report a case of this unusual
      entity and review the literature.

PMID- 19114956
TI  - Validation the Oral Health Impact Profile (OHIP-14sp) for adults in Spain.
AB  - OBJECTIVES: The oral health-related quality of life indicators are increasingly
      used to measure the impact of oral conditions on quality of life to complement
      clinical data in cross-sectional and longitudinal studies. One of the most
      internationally spread indicators is the Oral Health Impact Profile (OHIP-14),
      but it has still never been applied in Spain. The aim of this study was to
      validate the OHIP-14 for use among adults in Spain. STUDY DESIGN: A cross
      sectional study was performed in Granada (Spain). A consecutive sample (n=270) of
      the Regional Government staff visiting the Employment Risk Prevention Centre for
      a routine medical check-up participated in this study. All participants self
      completed the piloted OHIP-14sp and were examined according to World Health
      Organization methodology for caries, periodontal disease and prosthesis.
      Reliability analyses and validity tests were carried out to evaluate the
      psychometric properties of the OHIP-14sp by using two different methods of total
      scoring (i.e. the Additive and the Simple Count). RESULTS: The reliability
      coefficient (Cronbach's alpha) of the OHIP-14sp was above the recommended 0.7
      threshold and considered excellent (alpha: 0.89). Some subjective factors
      (perceived dental treatment need, complaints about mouth and self-rated oral
      satisfaction) were strongly associated with both total scoring methods of the
      OHIP-14sp, supporting the criterion, construct and convergent validity. Moreover
      the impact levels were mainly influenced by caries data, e.g., number of teeth
      requiring extraction (r = 0.21; p<0.01) and number of decayed visible teeth
      (between premolars) (r = 0.17; p<0.01). The prevalence of impacts was 80.7% using
      the occasional or more frequently threshold. The most prevalently affected OHIP
      domains were "psychological discomfort" (53.7%), "functional limitation" (51.1%)
      and "physical pain" (42.2%). CONCLUSIONS: The OHIP-14sp is a precise, valid and
      reliable instrument for assessing oral health-related quality of life among adult
      population in Spain.

PMID- 19114957
TI  - Curing effectiveness of resin composites at different exposure times using LED
      and halogen units.
AB  - OBJECTIVE: To compare the polymerization effectiveness of two resin composites
      cured with a quartz tungsten halogen (QTH) lamp or a light emitting diodes (LED)
      unit. STUDY DESIGN: Filtek Z250 (3M ESPE) and Spectrum TPH (Dentsply DeTrey)
      resin composites were placed in 9 mm deep and 4 mm wide metallic molds and cured
      using the QTH light Hilux 200 (Benlioglu) or the LED unit Smartlite IQ (Dentsply
      DeTrey) for 20 or 40 s (three specimens per group). Measurement of depth of cure
      was carried out by means of a scraping technique, according to ISO 4049. The
      microhardness measurements were performed using a calibrated Vickers indenter
      (100 g load, 30 s) at depths of 0.5, 1.5, 2.5, 3.5, 4.5 and 5.5 mm from the top
      of the composite in the same specimens. Results were analyzed by ANOVA, Student's
      t and Student-Newman-Keuls tests (p<0.05). RESULTS: Filtek Z250 exhibited higher
      depth of cure and Vickers microhardness values than Spectrum TPH under each
      experimental condition evaluated. Depth of cure and microhardness were not
      affected by the curing light used. However, hardness values were influenced by
      the interaction between curing light and exposure time. Specimens irradiated for
      20 s exhibited higher microhardness values when the LED curing light was used.
      Exposure time had no influence on the microhardness values for depths from 0.5 to
      2.5 mm. At higher depths, irradiation for 40 s produced greater microhardness
      values. CONCLUSIONS: Curing effectiveness of resin composite is not only
      dependent on the curing light unit. Results vary greatly with composite brand,
      thickness of the resin composite and the duration of the exposure.

PMID- 19114958
TI  - Clinical evaluation of a new artificial saliva in spray form for patients with
      dry mouth.
AB  - OBJECTIVES: To determine the efficacy of a new saliva substitute in spray form,
      for patients with dry mouth. STUDY DESIGN: Thirty-seven patients with dry mouth
      were selected (16 males and 21 females), with an age of over 60 years and meeting
      the following inclusion criteria: xerostomia and hyposialia confirmed by
      sialometry (resting whole saliva / stimulated whole saliva). A new artificial
      saliva in spray format was applied, with evaluation of the degree of improvement
      (VAS scale), frequency of application, time to improvement in minutes, duration
      in minutes, and assessment of organoleptic properties. RESULTS: Twenty of the 37
      patients showed almost immediate improvement after application. The mean number
      of applications/day was 3.89, with a mean duration of effect of 15.3 min. (65% >
      15 min.). The flavor was rated as pleasant by 18 patients. CONCLUSIONS:
      Application of the spray is simple and effective, affording immediate relief, and
      with reasonable acceptance among patients with dry mouth.

PMID- 19114959
TI  - Capsaicin blocks HIV protease inhibitor ritonavir-induced vascular dysfunction in
      porcine pulmonary arteries.
AB  - BACKGROUND: Highly active antiretroviral therapy (HAART) including HIV protease
      inhibitor ritonavir may be associated with the clinical complications including
      accelerated atherosclerosis and pulmonary artery hypertension. The objective of
      this study was to determine whether capsaicin, a major ingredient of hot pepper
      with antioxidative property, could effectively inhibit ritonavir-induced
      oxidative injury in porcine pulmonary arteries. MATERIAL/METHODS: Fresh porcine
      pulmonary artery rings were treated with ritonavir (15 microM), capsaicin (50
      microM) or both for 24 hours and, then, subjected to myograph analysis in
      response to vasoactive drugs including thromboxane A2 analog U-46619, bradykinin,
      and sodium nitroprusside (SNP). RESULTS: In response to U-46619 (3x10(-8) M),
      ritonavir-treated porcine pulmonary artery rings reduced the contraction by 15%
      compared with control rings. In response to bradykinin (10(-6) M), ritonavir
      treated rings showed a significant reduction of endothelium-dependent
      vasorelaxation by 32% compared with untreated control vessels (P<0.05, n=5,
      Student t-test). However, ritonavir treatment did not change endothelium
      independent vasorelaxation in response to SNP (10(-6) M). Capsaicin-treated
      vessel rings did not show any significant changes in response to U-46619,
      bradykinin, and SNP compared with untreated control vessels. More importantly,
      capsaicin co-cultured with ritonavir significantly blocked ritonavir-induced
      inhibition of endothelium-dependent vasorelaxation and contraction compared with
      ritonavir alone treatment in porcine pulmonary artery rings (P<0.05, n=5, Student
      t-test). CONCLUSIONS: Capsaicin effectively inhibits the detrimental effects of
      HIV protease inhibitor ritonavir on vasomotor functions of porcine pulmonary
      arteries. These findings may suggest that capsaicin could have clinical
      applications to prevent vascular and pulmonary complications of HAART drugs in
      HIV patients.

PMID- 19114960
TI  - Antitumor efficiency of the cytosine deaminase/5-fluorocytosine suicide gene
      therapy system on malignant gliomas: an in vivo study.
AB  - BACKGROUND: Suicide gene therapy, particularly that utilizing the cytosine
      deaminase/5-fluorocytosine (CD/5-FC) system, represents a novel and attractive
      methodology of cancer research. Mechanistically, the CD enzyme can convert the
      antifungal agent 5-FC into the antimetabolite agent 5-fluorouracil (5-FU),
      thereby killing tumor cells. The purpose of this study was to investigate the
      antitumor efficiency of the CD/5-FC system in malignant gliomas using a nude
      mouse model. MATERIAL/METHODS: The eukaryotic expression plasmid pCMV-CD was
      transfected into U251 malignant glioma cells. Resistant clones (labeled U251/CD
      cells) were subsequently isolated and further confirmed by reverse transcription
      polymerase chain reaction (RT-PCR), immunofluoroscence, and immunoblot. Then
      U251/CD cells were incubated with 5-FC at various concentrations to measure
      viability ratios as determined by the 3-(4,5-dimethylthiazol-2-yl)-2,5
      diphenyltetrazolium bromide (MTT) method. 5-FU concentrations in the media were
      measured by high-performance liquid chromatography (HPLC). Finally, the volumes
      and weights of tumors from glioma-bearing nude mice after 5-FC intervention were
      evaluated. RESULTS: The results revealed that the untreated U251 cells were
      insensitive to 5-FC whereas the U251/CD cells were highly sensitive. Apoptosis
      and cell death were observed on the U251/CD cells after 5-FC administration. HPLC
      analysis showed that 5-FU was detected in the U251/CD cell media. These in vivo
      animal data showed that the volumes and weights of the implanted tumors were
      dramatically decreased due to cell apoptosis and tumor necrosis. CONCLUSIONS: The
      in vivo results encourage a further investigation in a controlled trial on the
      treatment of malignant gliomas via the CD/5-FC gene therapy system.

PMID- 19114961
TI  - Rosiglitazone, a peroxisome proliferator-activated receptor gamma (PPARgamma)
      specific agonist, as a modulator in experimental acute pancreatitis.
AB  - BACKGROUND: The purpose of this experiment was to investigate the role of PPAR
      ligands in the course of inflammation and of rosiglitazone, a PPAR-gamma-specific
      agonist, on the course of experimental acute pancreatitis (EAP).
      MATERIAL/METHODS: EAP was induced by administration of 5% sodium taurocholate
      injected into the pancreatic duct. The inflammatory activity was evaluated by
      biochemical scores (alpha-amylase, lipase, aminotransferases, and bilirubin),
      morphological changes (determined by light microscopy, H+E stained), and
      immunohistochemical reactions (ICAM, nitrotyrosine). RESULTS: Rosilgitazone
      administered in the course of EAP at a dose 50 mg/kg p.o. decreased the intensity
      of morphological changes (edema, inflammatory infiltrates, necrosis, and
      erythrocyte extravasations). In the rosiglitazone-treated animals all the
      biochemical parameters of EAP were statistically significantly decreased.
      Immunohistochemical reactions against ICAM-1 and nitrotyrosine showed that
      rosiglitazone decreased the intensity of inflammatory reactions in the groups of
      treated animals. CONCLUSIONS: PPAR-gamma agonists modulate the course of the
      inflammatory reaction. The administration of rosiglitazone decreased the
      intensity of the inflammatory process in the course of sodium taurocholate
      induced EAP.

PMID- 19114962
TI  - The effect of an exon 12 polymorphism of the human thromboxane synthase (CYP5A1)
      gene in stroke patients.
AB  - BACKGROUND: To examine the prevalence of an exon 12 polymorphism on the human
      Thromboxane synthase (CYP5A1) gene. MATERIAL/METHODS: Using sequence-specific
      PCR, we examined the allelic prevalence in 237 Greek patients with ischemic
      strokes and in 171 controls. In addition, we compared the CYP5A1 allelic
      prevalence in 71 patients with stroke recurrence despite Aspirin use, in
      comparison with patients who have not experienced recurrent stroke while taking
      Aspirin. RESULTS: The frequencies of the CYP5A1*9 mutant (substitution of guanine
      by adenine near the heme-binding catalytic domain) and of the wild-type allele
      were 0.197 and 0.803, respectively; they did not differ significantly between
      stroke patients and controls. The wild-type allele was more frequent in the
      Cretan population compared to continental Greece (OR 1.80, 95% CI 1.19-2.74). The
      wild-type allele was more frequent among hypertensive and less frequent among
      diabetic stroke sufferers, respectively. The CYP5A1*9 mutant was significantly
      more prevalent among stroke patients with history of previous cerebrovascular
      attacks (p<0.01); and among those who failed secondary Aspirin prophylaxis even
      after adjusting for the common risk factors for cardiovascular disease (OR 1.49,
      95% CI 1.06-2.11). CONCLUSIONS: Allelic prevalence of the CYP5A1 exon 12 might
      differ between geographic areas within the same ethnic group, and is associated
      with particular characteristics of stroke patients. Allele mutations can abolish
      the enzymatic activity of thromboxane synthase, via impaired heme binding,
      associated with defective response to Aspirin used as secondary prevention, an
      effect independent from the conventional risk factors for cerebrovascular
      disease.

PMID- 19114963
TI  - Ethanol inhibited apoptosis-related RNA binding protein, Napor-3 gene expression
      in the prenatal rat brain.
AB  - BACKGROUND: Cell death and differentiations are the critical processes in
      developing fetal brain, where ethanol induces lots of changes in gene expression
      patterns of fetal nervous system leading to fetal alcohol syndrome (FAS). The
      objective of the present study was to observe whether maternal ethanol exposure
      can alter gene expression pattern in mother and in fetus during mid and late
      prenatal stage. MATERIAL/METHODS: 10% ethanol was orally applied to female
      Spraque-Dawley rats and fetuses were sacrificed on gestational day (GD) 19.5 and
      21.5. Total mRNA was isolated for differential-display PCR (DD-PCR) and sequence
      was analyzed to find out the homologous gene(s) using GenBank database of the
      BLAST program. Finally, the gene expression pattern in different maternal and
      fetal brain areas of the control and the ethanol treated groups were studied by
      RNase protection assay (RPA) and in situ hybridization. RESULTS: Out of several
      differentially expressed genes, apoptosis-related RNA binding protein (RBP),
      'Napor-3' mRNA expression was significantly inhibited by ethanol in fetal rat
      fore-, mid- and hind- brain, and adult rat cortex and hippocampus when compared
      with the untreated control. The cDNA analysis was further supported our result
      (accession: AF090697, 95% sequence homology). CONCLUSIONS: The age and area
      dependent suppression of apoptosis-related RBP, Napor-3 gene expression in
      proliferating fetal brain by maternal ethanol suggesting high susceptibility
      towards ethanol intake at the time of neuronal cell development and
      proliferation. Further, ethanol also affects maternal brain tissues that may be
      one of the reasons for ethanol-induce irreversible damage of the developing
      brain. The present study for the first time provides the evidence that Napor-3
      suppression by ethanol during mid and late stage fetal brain converts natural
      physiological event apoptosis into pathological process, which may be useful as a
      novel therapeutic approach towards FAS-associated developmental brain damage as a
      consequence of maternal drinking behavior.

PMID- 19114964
TI  - Efficacy of long-term, low-dose gonadotropin-releasing hormone agonist therapy
      (draw-back therapy) for adenomyosis.
AB  - BACKGROUND: The usefulness of long-term, low-dose gonadotropin-releasing hormone
      agonist (GnRHa; buserelin acetate) therapy, so-called draw-back therapy, for the
      treatment of adenomyosis was investigated not. MATERIAL/METHODS: A retrospective
      observational study was conducted covering the period between January 2003 and
      March 2008. The subjects consisted of 12 patients with adenomyosis who underwent
      draw-back therapy for 2 years and had previously received GnRHa. GnRHa was
      initiated at 900 microg/day (6 nasal sprays/day). When the CA-125 level
      normalized, the GnRHa dosage was adjusted to 150-750 microg/day to achieve a
      plasma estradiol (E2) concentration of 20-50 pg/ml (i.e., the therapeutic
      window). Pain during withdrawal bleeding and chronic pelvic pain were assessed
      using a visual analogue scale. In addition, bone mineral density (BMD) of the
      lumbar vertebrae was measured using dual-energy X-ray absorptiometry. RESULTS:
      The mean GnRHa dose during draw-back therapy was 435 microg/day (2.9 nasal
      sprays/day). The mean E2 level during draw-back therapy was 36.3+/-14.3 pg/ml.
      The intensity of chronic pelvic pain was significantly lower during draw-back
      therapy than before draw-back therapy, and was nearly eliminated in many patients
      (4.8+/-1.2 vs. 0.6+/-0.7, respectively [p=0.000]). Compared to the severity of
      vasomotor symptoms during previous regular GnRHa therapy, the severity of
      vasomotor symptoms during draw-back therapy was significantly lower (3.8+/-0.7 vs
      1.1+/-0.7, respectively [p=0.000]). The decrease in BMD during a 6-month course
      of treatment was 0.96+/-0.9%. CONCLUSIONS: GnRHa draw-back therapy allowed
      maintenance of plasma E2 levels within the therapeutic window. GnRHa can thus be
      administered for long periods of time while maintaining therapeutic effects on
      adenomyosis and suppressing adverse events.

PMID- 19114965
TI  - Lack of influence of glutathione S-transferase genotype profile on cancer
      susceptibility in smokers and nonsmokers.
AB  - BACKGROUND: The glutathione-S-transferase (GST) gene family has an important role
      in the biotransformation and detoxification of different xenobiotics and
      endogenous carcinogens. GST profile has been associated to an increased risk for
      several types of tumors in different populations, but ethnic stratification makes
      data interpretation difficult. The Brazilian population represents a unique model
      in which the types and frequencies of GST gene polymorphisms are less influenced
      by ethnicity. MATERIAL/METHODS: To evaluate the influence of GST profile in
      different age and gender groups regarding the risk of developing cancer and its
      relationship to smoking habit, the GSTT1, GSTM1, and GSTP1 genotypes of 785
      Brazilian patients with cancer and 873 cancer-free controls paired on the basis
      of sex, age, ethnicity, diet and exercise routine, lifetime occupational history,
      smoking history, general health conditions, and previous diseases were compared.
      RESULTS: A univariate logistic regression analysis demonstrated that age over 45
      years (p=0.0417) and smoking (p=0.0015) were related to cancer. Multivariate
      analysis confirmed the importance of advanced age in susceptibility to cancer
      (p=0.0001). It was also observed that smoking significantly increased the risk of
      cancer among individuals over 45 years old (OR: 1.825, 95%CI: 1.241-2.682).
      However, no correlation between risk of cancer, smoking habit, age, or gender and
      any of the studied GST polymorphisms was found. CONCLUSIONS: It is suggested that
      GST profile does not exert an important impact on the influence of tobacco
      smoking on cancer risk.

PMID- 19114966
TI  - The effect of vitamin E on the treatment of menstrual migraine.
AB  - BACKGROUND: Many women with migraine experience a change in migraine frequency
      associated with the menstrual cycle. This study was undertaken to study the
      effect of vitamin E as a prophylactic agent on women with menstrual migraine.
      MATERIAL/METHOD: During a placebo-controlled double-blinded trial, 72 women with
      menstrual migraine received placebo (identical in appearance to vitamin E) daily
      for five days, two days before to three days after menstruation for two cycles
      followed by a one-month wash-out and one vitamin E softgel (400 IU) daily for
      five days in the next two cycles. Each woman was evaluated monthly throughout the
      study and the daily headache severity, concomitant symptoms, and functional
      disability derived from questionnaires were compared between the vitamin E and
      the placebo treatment periods using four-point anchored scales. RESULTS: There
      were statistically significant differences in the pain severity and functional
      disability scales between the placebo and the vitamin E treatments (p<0.001).
      Vitamin E effect was also superior to placebo regarding photophobia, phonophobia,
      and nausea (p<0.05). CONCLUSIONS: Vitamin E is effective in relieving symptoms
      due to menstrual migraine.

PMID- 19114967
TI  - No relationship between the length of the left coronary artery main stem and the
      type of coronary vasculature in human fetuses from a morphological perspective.
AB  - BACKGROUND: The aim of this study was to evaluate whether the type of heart
      vasculature is in any way related to the length of the main stem of the left
      coronary artery. The study was inspired by publications describing a shorter main
      stem of the left coronary artery in adults with left coronary artery
      predominance, also associated with a worse clinical outcome. Such relationships
      have not been been examined in a fetus. A short main stem of the left coronary
      artery is thought to convey faster progression of atheromatosis in coronary
      arteries. MATERIAL/METHODS: This investigation was performed on 187 fetuses of
      both sexes at the Nicolaus Copernicus University Department of Histology and
      Embryology. Vasculature types were determined in line with criteria set by
      Adachi. All fetuses had been delivered naturally. None of them had any signs of
      malformations or developmental abnormalities. Prior to examination, all fetuses
      had been conserved for a 3-month period in 9% formaldehyde solution. Statistical
      analysis was carried out using Statistica software for Windows. RESULTS: The
      length of the left main stem was found to be related to the type of vasculature,
      though this relationship did not achieve statistical significance. There were no
      differences in relation to gender or type of vasculature or between analyzed sub
      groups. CONCLUSIONS: There was no relationship between the length of the main
      stem and dominance of the coronary artery in this study.

PMID- 19114968
TI  - Soluble cytokine receptors sTNFR I and sTNFR II, receptor antagonist IL-1ra, and
      anti-inflammatory cytokines IL-10 and IL-13 in the pathogenesis of systemic
      inflammatory response syndrome in the course of burns in children.
AB  - BACKGROUND: This is a prospective clinical study focusing on cytokine inhibitors
      (sTNFR I, sTNFR II, IL-1ra) and anti-inflammatory cytokines (IL-10, IL-13)
      following burn injury in children. The aim of the study was to evaluate the
      prognostic values of the selected cytokine-related molecules. MATERIAL/METHODS:
      Fifty-one patients (29 burned children and 22 controls) admitted to the
      Department of Pediatric Surgery and Oncology were included in this study. Serum
      sTNFR I, sTNFR II, IL-1ra, IL-10, IL-13, and CRP concentrations were evaluated
      twice using ELISA, the first determination being performed within 6-24 hrs after
      the burn and the second following completion of treatment and normalization of
      the CRP level. RESULTS: With the exception of IL-13, significantly higher
      cytokine and cytokine inhibitor levels were observed within 6-24 hours after burn
      compared with controls (p<0.05). Moreover, a significant attenuation of the burn
      induced increases in sTNFR I, sTNFR II, IL-1ra, and IL-10 concentrations was
      recorded after burn therapy (p<0.05). TNF-alpha soluble receptor levels
      correlated significantly with serum CRP concentrations. Similarly, the levels of
      sTNFR I, sTNFR II, and IL-1ra significantly correlated with TBSA of the burned
      children. CONCLUSIONS: The results confirm the involvement of these markers in
      the pathogenesis of SIRS in this clinical entity. Their monitoring simultaneously
      with CRP level allows evaluating the generalized inflammatory response and may
      clinically support diagnostic and prognostic methods.

PMID- 19114969
TI  - Decreased bone mineral density in men with metabolic syndrome alone and with type
      2 diabetes.
AB  - BACKGROUND: Metabolic syndrome is associated with decreased physical activity and
      increased incidence of diabetes. Bone Mineral density (BMD) is positively
      associated with physical activity. Lower BMD is a risk factor for bone fractures.
      Whether subjects with metabolic syndrome alone show early signs of lower BMD and
      osteoporosis similar to those present in diabetic is not known. MATERIAL/METHODS:
      This cross-sectional study in male veterans examined the BMD in 3458 non-diabetic
      men and 735 men with type 2 diabetes. In addition, the BMD changes in non
      diabetic men without any metabolic syndrome were compared with non-diabetic men
      with metabolic syndrome as established by the criteria of the Adult Treatment
      Panel III. RESULTS: BMD of hip was significantly lower and incidence of
      osteoporosis higher in diabetic subjects compared with age and body mass index
      (BMI) matched non-diabetic subjects. BMD of AP spine was significantly higher in
      diabetic subjects compared with non-diabetics but similar when subjects were
      matched for BMI. Men with metabolic syndrome alone had higher osteoporosis and
      lower BMD of hip compared with those without metabolic syndrome. CONCLUSIONS: The
      BMD of hip is lower in diabetics compared with age and BMI-matched non-diabetic
      men, and its level is similar in age and BMI-matched diabetics and non-diabetic
      men with metabolic syndrome. This suggests that both diabetes and metabolic
      syndrome are associated independently with higher osteoporosis and lower BMD of
      hip and are risk factors for increased incidence of hip fractures in men.

PMID- 19114970
TI  - Acute and diffuse postoperative bleeding after free latissimus dorsi flap--Factor
      XIII deficiency: a case report and review of the literature.
AB  - BACKGROUND: Factor XIII deficiency is a rare inherited bleeding disorder that is
      often difficult to diagnose. As there are no standard screening tests established
      patients with Factor XIII deficiency are not correctly identified. Especially
      postoperative bleeding and haemorrhage after difficult plastic reconstructive
      operations such as free flap transfer may lead the plastic surgeon to the wrong
      diagnosis. This again leads to the wrong indication such as revision with the aim
      to find a surgical origin of bleeding. Instead a haematological deficiency such
      as Factor XIII is the reason for acute postoperative bleeding and haemorrhage.
      CASE REPORT: We report the case of a 69-year old Caucasian male who received a
      free latissimus dorsi flap to the right knee after osteomyelitis and infection of
      a knee total endoprothesis. The patient had severe postoperative bleeding and
      haemorrhage from all 8 drains including the donor side of the split thickness
      skin graft area. Shortly before the indication of performing a revision and
      trying to find the surgical origin of bleeding a factor XIII test was performed.
      The results showed a high deficiency of factor XIII which was immediately
      replaced by 2500 Units (i.E.) Fibrogammin. Within 12 hours the bleeding rapidly
      reduced and no revision was necessary. CONCLUSIONS: Postoperative acute but
      diffuse bleeding after free flap operations in plastic surgery may not be all due
      to insufficient operative techniques.

PMID- 19114971
TI  - Experiences with a long-term treatment of a massive gluteal acne inversa with
      infliximab in Crohn's disease.
AB  - BACKGROUND: In 40% of all cases of Crohn's disease fistulas emerge during the
      course of disease. Nevertheless, acne inversa has to be taken into account as an
      infrequent differential diagnosis. Infliximab as an antibody against the pro
      inflammatory mediator TNF-alpha is active in cases of acute Crohn's disease,
      concomitant fistulas and cutaneous manifestations. CASE REPORT: We report on the
      case of a 54-year-old patient suffering for five years from a severe suppurative
      fistuling cutaneous disease concomitant to Crohn's disease. At the start of
      treatment the histological findings of a specimen presented chronically fibrosing
      lymphoplasmacellular dermatitis with both a very high number of plasma cells and
      a burrow-like fistula system. Due to superinfection the treatment was at first
      based on the administration of intravenous and oral doses of antibiotic agents,
      followed by a treatment course of 14 months with methotrexate and seven
      applications of infliximab. During the Crohn's disease, which was accompanied by
      persisting concomitant discomforts, an extensive surgical sanitation of the
      fistulous tracts was performed. Acne inversa was diagnosed in the subsequent
      histological analysis of the operative specimen. CONCLUSIONS: Acne inversa is a
      very rare cutaneous disease. Several case reports describe the successful
      treatment of acne inversa concomitant to Crohn's disease using anti-TNF-alpha
      antibodies. The long-term course of the case presented here shows that the non
      response to infliximab might be caused by both the long duration and the distinct
      grade of seriousness of the acne inversa.

PMID- 19114972
TI  - A complication of soft tissue graft tibial fixation with the IntraFix device.
AB  - BACKGROUND: One potential complication of interference devices to fix anterior
      cruciate ligament (ACL) grafts is divergence between the implant and the graft
      tunnel. Tunnel-screw divergence >15-30 degrees significantly reduces graft-tunnel
      fixation and may compromise the stability of the knee. CASE REPORT: A
      complication of the IntraFix device is presented. A 43-year-old male sustained a
      primary ACL reconstruction. The autologous hamstring graft was fixed in the tibia
      with the IntraFix device. The procedure went without apparent incidents or
      complications. During postoperative follow-up he developed pain and crepitus over
      the anteromedial aspect of the operated knee. A flexion contracture slowly
      developed up to 10 degrees and did not improve with aggressive physiotherapy. At
      eight postoperative weeks, second-look arthroscopy was performed. The
      intraoperative findings were a healthy-looking ACL graft and a grade III chondral
      injury in the medial femoral condyle (MFC) caused by the tip of the IntraFix
      device, which protruded through the medial tibial plateau. During flexion
      extension motion of the knee, the tip eroded the chondral surface of the MFC.
      This was treated with mechanical and thermal chondroplasty and the tip of the
      IntraFix device was burred flat to match the surface of the medial tibial
      plateau. The patient's symptoms improved. CONCLUSIONS: Divergence of the
      interference screws in the femur is not uncommon, but on the tibia it is rare.
      Although this technical error did not affect stability, it did produce
      intrarticular injury. Strict adherence to the surgical technique is recommended
      and several hints on how to avoid complications with this implant are suggested.

PMID- 19114974
TI  - The autistic mind: a case study.
AB  - BACKGROUND: Despite years of intensive research, there is much about autism that
      remains theoretically and practically difficult to understand. There are
      presently three main theories: (1) defect of theory of mind, (2) executive
      dysfunction, and (3) lack of central coherence, i.e. an inability to integrate
      sensation and behavior into complex and sensible wholes. CASE REPORT: The
      patient, Damian S, born 1993, was diagnosed in early childhood with profound
      autism. He has been closely observed longitudinally by the first author, who is
      his therapist. Despite the absence of noticeable improvement in standard
      psychometric tests, he has shown considerable clinical progress. However, he
      continues to have difficulty in making and maintaining contact with others: he
      converses spontaneously only with his father and his teacher, and interacts with
      other persons (including his mother) only in the presence of one of these two
      persons. However, he has learned to use a computer to communicate. Samples of
      dialogue are provided to help illuminate how he thinks. CONCLUSIONS: Despite his
      profound autism, Damian displays awareness of and concern for the thoughts and
      feelings of others. He is also able to solve problems. On the basis of this and
      other observations, the authors suggest that the "central coherence" theory
      better explains the available observations and data.

PMID- 19114973
TI  - Neurotoxicity during ifosfamide treatment in children.
AB  - BACKGROUND: Neurotoxicity has been reported in about 5% of children treated with
      ifosfamide for tumors not involving the central nervous system. The entity of
      ifosfamide neurotoxicity can be of different degree, from very light and
      transient to fatal. CASE REPORTS: All cases of ifosfamide neurotoxicity recorded
      at the Pediatric Hematology and Oncology Unit in the 15-year period between 1989
      and 2003 are reported. Five cases of neurotoxicity occurring during or
      immediately after ifosfamide infusion were recorded in children with both solid
      tumors or leukemia. The drug was administered in different chemotherapeutic
      associations and dosages. Concomitant clinical conditions possibly playing a role
      as risk factors were the administration of other neurotoxic drugs, the presence
      of cerebral metastasis, a subclinical lysis syndrome, and altered respiratory
      function. Symptoms were transient in all cases and consisted in all but one of
      partial or generalized seizures. In four cases the treatment was continued,
      substituting ifosfamide with cyclophosphamide. CONCLUSIONS: Particularly in
      patients presenting risk factors, we advise paying attention to the risk of
      ifosfamide neurotoxicity and rapidly suspending the drug administration to avoid
      irreparable damage to the central nervous system. Thereafter the treatment can be
      reassessed. If ifosfamide is considered the best option for the given case, it
      could be safely readministered in association with methylene blue or thiamine. If
      encephalopathy reappears, substitution of ifosfamide with cyclophosphamide could
      offer the same opportunities of cure to the patient.

PMID- 19114975
TI  - Influence of endotracheal tube bore on tidal volume during high frequency
      oscillatory ventilation: a model lung study.
AB  - BACKGROUND: In adults, the influence of endotracheal tube bore on tidal volume
      (VT) during high-frequency oscillatory ventilation (HFOV) has been little
      studied. MATERIAL/METHODS: Via full-length 6, 7, 8, and 9 mm internal diameter
      (ID) endotracheal tubes (ETTs), a model lung (TTL, Michigan Instruments, MI) was
      ventilated using a high-frequency oscillator designed for adult patients (R100;
      Metran, Japan). Oscillation settings were: frequency, 5, 7, and 9 Hz; mean airway
      pressure, 15 cmH2O; oxygen inspiratory fraction, 0.21. At each setting:
      oscillator pressure swing was set at maximum; and each test combination was
      conducted with the model-lung compliance set at 20 and 50 mL/cmH2O. During the
      trials, a position sensor attached to the model-lung upper surface provided
      analog electrical signals for lung movement that were converted to VT evaluation
      data. Pressure and volume signals were digitized using an analog-to-digital
      converter and recorded in a computer. At each setting, three waveforms were
      analyzed and the average value used. RESULTS: At each setting, measured VT was
      proportional to ETT internal cross-sectional area (CSA). Regression analysis of
      VT showed correlation with the CSA, as expressed by formula, y=2.173x where x is
      CSA and y is VT (R2=0.99, p<0.001) at 5 Hz and compliance of 50 cmH2O.
      CONCLUSIONS: In an adult-simulating model lung, VT during HFOV varies in
      proportion to ETT CSA.

PMID- 19114976
TI  - Diagnostic and prognostic markers in infants with disseminated neuroblastoma: a
      retrospective analysis from the Italian Cooperative Group for Neuroblastoma.
AB  - BACKGROUND: One fourth of infants with disseminated neuroblastoma experience
      unfavorable outcome. Treatment strategies vary and are based on clinical
      characteristics at diagnosis which lead to the definition of stage 4 or 4s. To
      identify the distribution and effect of different prognostic factors, a series of
      such infants diagnosed in Italy between 1991-1999 was reviewed. MATERIAL/METHODS:
      Data were retrospectively retrieved from the Italian Neuroblastoma Registry. One
      hundred infants, 32 stage 4 and 68 stage 4s, were eligible. Clinical and
      biological characteristics evaluated at diagnosis for their impact on survival
      were demographics, primary site, urinary excretion of vanillylmandelic and
      homovanillic acids, serum neuron specific enolase, LDH, and ferritin together
      with analysis for MYCN gene, DNA index, and 1p36 chromosome. RESULTS: Stage 4
      prevailed in the second six months of life and stage 4s in the first six months.
      Events were distributed over two years in stage 4, but occurred very early in
      stage 4s patients. Survival was respectively 72% and 77.9%. Unfavorable factors
      were MYCN amplification for both stages, elevated NSE and LDH and normal VMA for
      stage 4, and di-tetraploid DNA for stage 4s. CONCLUSIONS: The frequency of stage
      4s was greater than stage 4. MYCN amplification was the most unfavorable
      prognostic factor. Survival was similar to previous series, confirming that a
      part of such infants cannot be cured by current therapies.

PMID- 19114977
TI  - Improved screening for growth hormone deficiency using logical analysis data.
AB  - BACKGROUND: The growth hormone (GH) Research Society proposed criteria based on
      auxological parameters (height, difference between target and actual heights,
      growth rate) to predict GH deficiency (GHD) followed by GH stimulation tests.
      These criteria are very sensitive but not specific enough. The objective of this
      study was to improve screening for GHD, so reducing the need for stimulation
      tests. MATERIAL/METHODS: The patients were divided into three groups: Group 1
      (n=54) with GHD and pituitary stalk interruption syndrome; Group 2 (n=104) with a
      normal GH peak after pharmacological and sleep tests; Group 3 (n=19) with
      transient GHD. The GHD diagnosis was based on the parameters proposed by the GH
      Research Society to evaluate the GH secretion, first alone and then plus plasma
      insulin-like growth factor (IGF) I concentrations. Data were analysed using the
      logical analysis of data framework. RESULTS: Screening can be achieved using a
      simple graph based on IGF I and the growth rate (GR): (1) all patients below a
      given line (GR < or =-7.3 - 1.3xIGF (SDS)) had GHD; (2) all but two patients
      above another given line (GR >-4.5 + 6.4/(IGF + 4.5) (SDS)) did not have GHD; (3)
      in-between, patients in a "gray area" cannot be diagnosed using only growth rate
      and IGF I. Most of the transient GHD were in or near the "gray area".
      CONCLUSIONS: Short children can be screened for GHD using growth rate and IGF I.
      Magnetic resonance imaging can then be used to detect pituitary stalk
      interruption syndrome or a tumor.

PMID- 19114978
TI  - Perception of stress and quality of life in overweight and obese people-
      implications for preventive consultancies in primary care.
AB  - BACKGROUND: The increasing prevalence of obesity requires especially primary
      health care providers to act. General Practitioners (GP) in particular have the
      opportunity to motivate patients in early risk stages to follow weight reduction
      programmes before manifestation of associated diseases. In order to conduct
      preventive consultancies it is necessary to explore the individual physical and
      mental health status of patients. Aim of this study was to examine quality of
      life and perceived level of stress in overweight and obese patients treated in
      primary care. MATERIAL/METHODS: 123 patients, following a health Check up
      realized by their GP, rated self- reported questionnaires regarding quality of
      life and perceived level of stress (SF-12, PSS). Following descriptive analysis,
      differences in dependent variables related to BMI, sex and age were tested using
      ANOVA and regression analysis (SPSSv15.0). RESULTS: Restrictions in all
      parameters of mental health for overweight and obese patients in primary care
      were shown. Especially patients with a BMI above 30 kg/m2 reported a decreased
      level of quality of life. CONCLUSIONS: Health care providers should be aware of
      cumulative restrictions in mental health of their overweight patients. The
      findings provide essential implications for all health care professionals in
      primary care doing preventive consultancies with obese clients.

PMID- 19114979
TI  - Comparison of the severity of traumatic brain injuries in pedestrians and
      occupants of motor vehicles admitted to Firat health center: a five-year series
      in an Eastern Turkish city.
AB  - BACKGROUND: Traumatic brain injury is the leading cause of death of people in
      motor vehicle (MV) accidents, which have been increasing in number in developing
      countries. A retrospective study was undertaken to evaluate all cases admitted to
      the emergency department of the authors' institution with suspected injury after
      involvement in a MV-related accident between January 2000 and January 2005.
      MATERIAL/METHODS: During the study period a total of 2014 cases were admitted:
      1258 were occupants of motor vehicles and 756 were pedestrians. Cases with
      traumatic brain injury were evaluated with respect to gender, age, Glasgow Coma
      Scales (GCS), and death. RESULTS: Five hundred thirty-two of the cases (386 male,
      146 female, mean age: 26.8+/-20.3 years) involved in MV accidents experienced
      traumatic brain injuries, of which 299 were MV occupants and 233 were
      pedestrians. The pediatric (< or =16 years: 65.4%) and elderly (> or =65 years:
      64.7%) groups were frequently involved as pedestrians in MV accidents; adults 17
      64 years of age were involved as pedestrians at a lower rate (25.4%, p<0.001).
      The GCS values of the pedestrian victims were significantly lower than those of
      the MV occupants on admission (p<0.001). CONCLUSIONS: The results show that
      improvements in car safety have reduced life-threatening conditions for occupants
      of motor vehicles, but this does not include pedestrian safety. There is great
      need for practical strategies to reduce or prevent MV accident-related injuries
      among pedestrians, especially for the pediatric and elderly groups who are most
      exposed to these injuries.

PMID- 19114980
TI  - Roles and mechanisms of copper transporting ATPases in cancer pathogenesis.
AB  - Copper (Cu) is an essential trace element for cell metabolism as a cofactor to
      many key metabolic enzymes. Numerous physiological processes rely on the adequate
      and timely transport of copper ions mediated by copper-transporting ATPases (Cu
      ATPases), which are essential for human cell growth and development. Inherited
      gene mutations of ATP7A and ATP7B result in clinical diseases related to damage
      in the multiple organ systems. Increased expression of these genes has been
      recently observed in some human cancer specimens, and may be associated with
      tumorigenesis and chemotherapy resistance. However, underlying mechanisms of Cu
      ATPases in human cancer progression and treatment are largely unknown. In this
      review, we summarize current progress on the copper transport system, the
      structural and functional properties of the Cu-ATPases, ATP7A and ATP7B, in
      copper homeostasis, and their roles in anti-tumor drug resistance and cancer
      metastasis. This review provides valuable information for clinicians and
      researchers who want to recognize the newest advances in this new field and
      identify possible lines of investigation in copper transport as important
      mediators in human physiology and cancer.

PMID- 19114981
TI  - BRAVO wireless 48 hour pH-metric system.
AB  - The monitoring pH exposition in the esophagus plays an important role in the
      diagnosis of gastro-esophageal reflux disease (GERD). Recently, a new wireless
      method for intraesophageal pH measurement called the BRAVO system has been
      introduced for clinical application. This wireless system provides data on pH
      exposure of the esophagus through a small capsule clipped at the oesophageal
      mucosa. Since clinical introduction several studies have been published about
      safety, reliability, patient comfort and different clinical applications. This
      article provides an overview of different methods of capsule placement,
      complications, quality of the recorded data as well as future applications of the
      BRAVO system.

PMID- 19114982
TI  - Neurobiological principles in the etiopathogenesis of disease: when diseases have
      a head.
AB  - There is no doubt that the nervous system is involved in the etiopathogenesis of
      various pathological states and diseases. Interactions between the nervous,
      endocrine, and immune systems might represent the anatomical and functional basis
      for understanding the pathways and mechanisms that enable the brain to modulate
      the progression of disease. The aim of this article is to encourage us to shift
      our current opinion of the etiopathogenesis of disease to one of highly complex
      interactions between peripheral tissues and the brain and in this way introduce
      new diagnostic and therapeutic approaches.

PMID- 19114983
TI  - Research reflections.
AB  - Dr Switzer received D.V.M, from Texas A and M, in 1948, M.S. and a Ph.D, from
      Iowa State University in 1951 and 1954 and the Dr.h.c. from the University of
      Vienna, in 1979. He was Professor of Iowa State University, Veterinary Medical
      Research Inst, during 1961-74. He later became the Associate Dean for Research,
      ISU College of Veterinary Medicine, 1974-90. In 1990 he became Distinguished
      Professor emeritus, Iowa State University, 1990 and Associate Dean emeritus, in
      1990 to the present. He has won the following honors and awards: Borden
      Scholarship Award, Honorary Master Swine Producer, ISU Faculty Citation, ISU
      Distinguished Professor, American Feed Manufacturers Vet. Med. Research Award,
      Iowa Inventors' Hall of Fame, National Hog Farmer Award, Gamma Sigma Delta Award,
      International Award of Merit, Gamma Sigma Delta, Howard W. Dunne Memorial Award,
      Iowa Veterinarian of the year, 1988 in addition to several others. Switzer
      Research Award established at ISU College of Veterinary Medicine, Selected as one
      of the 150 most influential faculty members in the 150 year history of ISU,
      Vaccines developed by W. P. Switzer were selected as one of the 150 most valuable
      contributions in the history of ISU. DR. Switzer's patents: A) Use of
      Sulfonamides for Treatment of Atrophic Rhinitis in Swine; B) Vaccine for Control
      of Atrophic Rhinitis in Swine, and xx Vaccine for Control and Prevention of
      Kennel Cough in Dogs. He has also served on the following Advisory Boards: A)
      Animal Health Advisor, Merck and Co, five years; B) Animal Health Advisor,
      Pfizer, Inc, six years; and C) Animal Health Advisor, Diamond-Shamrock, two
      years.

PMID- 19114984
TI  - PTK787/ZK22258 attenuates stellate cell activation and hepatic fibrosis in vivo
      by inhibiting VEGF signaling.
AB  - Liver fibrosis due to hepatic stellate cell (HSC) activation represents a common
      response to chronic liver injury. PTK787/ZK222584 (PTK/ZK) is a pan-VEGFR
      tyrosine kinase inhibitor. The aim of this study was to examine the effect of
      PTK/ZK in liver fibrosis. In primary HSCs, PTK/ZK inhibited the expression of
      alpha-smooth muscle actin (alpha-SMA), collagen, tissue inhibitor of
      metalloproteinase-1 (TIMP-1), as well as cell proliferation, migration and actin
      filament formation. PTK/ZK-induced apoptosis of HSCs, which was correlated with
      increased caspase-3 activation and suppressed Bcl-2 expression. PTK/ZK also
      induced cell cycle arrest, accompanied by increasing the expression of p27(Kip1)
      and downregulation of cyclin D1 and cyclin E. PTK/ZK significantly inhibited
      vascular endothelial growth factor (VEGF) expression, as well as VEGF-simulated
      cell proliferation and phosphorylation of Akt in activated HSCs. In a murine
      fibrotic liver, PTK/ZK attenuated collagen deposition and alpha-SMA expression in
      carbon tetrachloride-induced fibrosis in both a 'prevention' and 'treatment'
      dosing scheme. These beneficial effects were associated with reduced
      phosphorylation of Akt and suppressed mRNA expression of procollagen-(I), TIMP-1,
      matrix metalloproteinase-9 and CD31. These findings provide novel insights into
      the potential value of blocking VEGF signaling by a small molecule tyrosine
      kinase inhibitor in treating hepatic fibrosis.

PMID- 19114985
TI  - Modulation of vascular endothelial function by low-density lipoprotein
      cholesterol with aging: influence of habitual exercise.
AB  - BACKGROUND: Aging is associated with reduced endothelium-dependent dilation (EDD)
      and increased risk for cardiovascular disease (CVD), but the mechanisms are
      incompletely understood. Clinically elevated plasma low-density lipoprotein
      cholesterol (LDL-C) is associated with impaired EDD. The purpose of this study
      was to determine whether circulating LDL-C within the "normal" range modulates
      EDD in healthy older adults and whether young age or habitual aerobic exercise
      protects against this adverse effect. METHODS: In 83 healthy men with
      optimal/near optimal LDL-C (<130 mg/dl) or borderline high LDL-C (130-159 mg/dl),
      EDD (brachial artery flow-mediated dilation, FMD), and endothelium-independent
      dilation (sublingual glyceryl trinitrate, GTN) were assessed. RESULTS: FMD was
      35% lower in older nonexercising men with borderline high LDL-C vs. optimal/near
      optimal LDL-C (3.1 +/- 0.5 vs. 4.8 +/- 0.4%Delta, P < 0.05), whereas the GTN
      response did not differ (P = 0.86). In contrast, FMD was similar between groups
      of young nonexercising men and between groups of older exercising men differing
      in LDL-C (P = 0.89-0.95). FMD was inversely related to LDL-C among the older
      nonexercising men (r = -0.43, P < 0.001), whereas there was no relation in the
      other groups (P > 0.05). CONCLUSIONS: Borderline high plasma LDL-C is associated
      with impaired EDD in older sedentary men, but not in young sedentary or older
      exercising men. Thus, modest elevations in plasma LDL-C within the normal range
      may contribute to the increased risk of CVD in sedentary older men by
      exacerbating vascular endothelial dysfunction, whereas resistance to this adverse
      influence may help explain the enhanced endothelial function and reduced CVD risk
      associated with young age and regular aerobic exercise.

PMID- 19114986
TI  - Epigenetic control of FOXP3 expression: the key to a stable regulatory T-cell
      lineage?
AB  - Regulatory T (T(Reg)) cells constitute a unique T-cell lineage that has a crucial
      role in immunological tolerance. Several years ago, forkhead box P3 (FOXP3) was
      identified as the transcription factor that was responsible for determining the
      development and function of these cells. However, the underlying mechanisms that
      are involved in the regulation of the FOXP3 gene remain unclear and therefore
      preclude accurate identification and manipulation of T(Reg) cells. In this
      Progress article, we summarize recent advances in understanding how FOXP3
      expression is controlled and highlight evidence suggesting that epigenetic
      regulation of the FOXP3 locus contributes to its role as a lineage-specification
      factor.

PMID- 19114987
TI  - Singleton deletions throughout the genome increase risk of bipolar disorder.
AB  - An overall burden of rare structural genomic variants has not been reported in
      bipolar disorder (BD), although there have been reports of cases with
      microduplication and microdeletion. Here, we present a genome-wide copy number
      variant (CNV) survey of 1001 cases and 1034 controls using the Affymetrix single
      nucleotide polymorphism (SNP) 6.0 SNP and CNV platform. Singleton deletions
      (deletions that appear only once in the dataset) more than 100 kb in length are
      present in 16.2% of BD cases in contrast to 12.3% of controls (permutation
      P=0.007). This effect was more pronounced for age at onset of mania <or=18 years
      old. Our results strongly suggest that BD can result from the effects of multiple
      rare structural variants.

PMID- 19114988
TI  - Serial imaging of human embryonic stem-cell engraftment and teratoma formation in
      live mouse models.
AB  - Two new types of lentiviral vectors expressing a reporter transgene encoding
      either firefly luciferase (fLuc) for bioluminescence imaging or the HSV1
      thymidine kinase (HSV1-TK) for radiopharmaceutical-based imaging were constructed
      to monitor human embryonic stem cell (hESC) engraftment and proliferation in live
      mice after transplantation. The constitutive expression of either transgene did
      not alter the properties of hESCs in the culture. We next monitored the formation
      of teratomas in SCID mice to test (1) whether the gene-modified hESCs maintain
      their developmental pluripotency, and (2) whether sustained reporter gene
      expression allows noninvasive, whole-body imaging of hESC derivatives in a live
      mouse model. We observed teratoma formation from both types of gene-modified
      cells as well as wild-type hESCs 2-4 months after inoculation. Using an optical
      imaging system, bioluminescence from the fLuc-transduced hESCs was easily
      detected in mice bearing teratomas long before palpable tumors could be detected.
      To develop a noninvasive imaging method more readily translatable to the clinic,
      we also utilized HSV1-TK and its specific substrate, 1-(2'-deoxy-2'-fluoro-beta-D
      arabinofuranosyl)-5-[(125)I]iodouracil ([(125)I]FIAU), as a reporter/probe pair.
      After systemic administration, [(125)I]FIAU is phosphorylated only by the
      transgene-encoded HSV1-TK enzyme and retained within transduced (and
      transplanted) cells, allowing sensitive and quantitative imaging by single-photon
      emission computed tomography. Noninvasive imaging methods such as these may
      enable us to monitor the presence and distribution of transplanted human stem
      cells repetitively within live recipients over a long term through the expression
      of a reporter gene.

PMID- 19114989
TI  - Ski and SnoN, potent negative regulators of TGF-beta signaling.
AB  - Ski and the closely related SnoN were discovered as oncogenes by their ability to
      transform chicken embryo fibroblasts upon overexpression. While elevated
      expressions of Ski and SnoN have also been reported in many human cancer cells
      and tissues, consistent with their pro-oncogenic activity, emerging evidence also
      suggests a potential anti-oncogenic activity for both. In addition, Ski and SnoN
      have been implicated in regulation of cell differentiation, especially in the
      muscle and neuronal lineages. Multiple cellular partners of Ski and SnoN have
      been identified in an effort to understand the molecular mechanisms underlying
      the complex roles of Ski and SnoN. In this review, we summarize recent findings
      on the biological functions of Ski and SnoN, their mechanisms of action and how
      their levels of expression are regulated.

PMID- 19114990
TI  - Non-Smad pathways in TGF-beta signaling.
AB  - Transforming growth factor-beta utilizes a multitude of intracellular signaling
      pathways in addition to Smads to regulate a wide array of cellular functions.
      These non-canonical, non-Smad pathways are activated directly by ligand-occupied
      receptors to reinforce, attenuate, or otherwise modulate downstream cellular
      responses. These non-Smad pathways include various branches of MAP kinase
      pathways, Rho-like GTPase signaling pathways, and phosphatidylinositol-3
      kinase/AKT pathways. This review focuses on recent advances in the understanding
      of the molecular and biochemical mechanisms of non-Smad pathways. In addition,
      functions of these non-Smad pathways are also discussed.

PMID- 19114992
TI  - Nucleocytoplasmic shuttling of Smad proteins.
AB  - Nuclear accumulation of active Smad complexes is crucial for transduction of
      transforming growth factor beta (TGF-beta)-superfamily signals from transmembrane
      receptors into the nucleus. It is now clear that the nucleocytoplasmic
      distributions of Smads, in both the absence and the presence of a TGF-beta
      superfamily signal, are not static, but instead the Smads are continuously
      shuttling between the nucleus and the cytoplasm in both conditions. This article
      presents the evidence for continuous nucleocytoplasmic shuttling of Smads. It
      then reviews different mechanisms that have been proposed to mediate Smad nuclear
      import and export, and discusses how the Smad steady-state distributions in the
      absence and the presence of a TGF-beta-superfamily signal are established.
      Finally, the biological relevance of continuous nucleocytoplasmic shuttling for
      signaling by TGF-beta superfamily members is discussed.

PMID- 19114991
TI  - Phospho-control of TGF-beta superfamily signaling.
AB  - Members of the transforming growth factor-beta (TGF-beta) family control a broad
      range of cellular responses in metazoan organisms via autocrine, paracrine, and
      endocrine modes. Thus, aberrant TGF-beta signaling can play a key role in the
      pathogenesis of several diseases, including cancer. TGF-beta signaling pathways
      are activated by a short phospho-cascade, from receptor phosphorylation to the
      subsequent phosphorylation and activation of downstream signal transducers called
      R-Smads. R-Smad phosphorylation state determines Smad complex
      assembly/disassembly, nuclear import/export, transcriptional activity and
      stability, and is thus the most critical event in TGF-beta signaling.
      Dephosphorylation of R-Smads by specific phosphatases prevents or terminates TGF
      beta signaling, highlighting the need to consider Smad (de)phosphorylation as a
      tightly controlled and dynamic event. This article illustrates the essential
      roles of reversible phosphorylation in controlling the strength and duration of
      TGF-beta signaling and the ensuing physiological responses.

PMID- 19114993
TI  - Roles of TGF-beta family signaling in stem cell renewal and differentiation.
AB  - Transforming growth factor (TGF)-betas and their family members, including bone
      morphogenetic proteins (BMPs), Nodal and activins, have been implicated in the
      development and maintenance of various organs, in which stem cells play important
      roles. Stem cells are characterized by their ability to self-renew and to
      generate differentiated cells of a particular tissue, and are classified into
      embryonic and somatic stem cells. Embryonic stem (ES) cells self-renew
      indefinitely and contribute to derivatives of all three primary germ layers. In
      contrast, somatic stem cells, which can be identified in various adult organs,
      exhibit limited abilities for self-renewal and differentiation in most cases. The
      multi-lineage differentiation capacity of ES cells and somatic stem cells has
      opened possibilities for cell replacement therapies for genetic, malignant and
      degenerative diseases. In order to utilize stem cells for therapeutic
      applications, it is essential to understand the extrinsic and intrinsic factors
      regulating self-renewal and differentiation of stem cells. More recently, induced
      pluripotent stem (iPS) cells have been generated from mouse and human fibroblasts
      that resemble ES cells via ectopic expression of four transcription factors. iPS
      cells may have an advantage in regenerative medicine, since they overcome the
      immunogenicity and ethical controversy of ES cells. Moreover, recent studies have
      highlighted the involvement of cancer stem cells during the formation and
      progression of various types of cancers, including leukemia, glioma, and breast
      cancer. Here, we illustrate the roles of TGF-beta family members in the
      maintenance and differentiation of ES cells, somatic stem cells, and cancer stem
      cells.

PMID- 19114994
TI  - TGF-beta signaling in vascular biology and dysfunction.
AB  - Transforming growth factor (TGF)-beta family members are multifunctional
      cytokines that elicit their effects on cells, including endothelial and mural
      cells, via specific type I and type II serine/threonine kinase receptors and
      intracellular Smad transcription factors. Knock-out mouse models for TGF-beta
      family signaling pathway components have revealed their critical importance in
      proper yolk sac angiogenesis. Genetic studies in humans have linked mutations in
      these signaling components to specific cardiovascular syndromes such as
      hereditary hemorrhagic telangiectasia, primary pulmonary hypertension and Marfan
      syndrome. In this review, we present recent advances in our understanding of the
      role of TGF-beta receptor signaling in vascular biology and disease, and discuss
      how this may be applied for therapy.

PMID- 19114995
TI  - Low density lipoproteins as circulating fast temperature sensors.
AB  - BACKGROUND: The potential physiological significance of the nanophase transition
      of neutral lipids in the core of low density lipoprotein (LDL) particles is
      dependent on whether the rate is fast enough to integrate small (+/-2 degrees C)
      temperature changes in the blood circulation. METHODOLOGY/PRINCIPAL FINDINGS:
      Using sub-second, time-resolved small-angle X-ray scattering technology with
      synchrotron radiation, we have monitored the dynamics of structural changes
      within LDL, which were triggered by temperature-jumps and -drops, respectively.
      Our findings reveal that the melting transition is complete within less than 10
      milliseconds. The freezing transition proceeds slowly with a half-time of
      approximately two seconds. Thus, the time period over which LDL particles reside
      in cooler regions of the body readily facilitates structural reorientation of the
      apolar core lipids. CONCLUSIONS/SIGNIFICANCE: Low density lipoproteins, the
      biological nanoparticles responsible for the transport of cholesterol in blood,
      are shown to act as intrinsic nano-thermometers, which can follow the periodic
      temperature changes during blood circulation. Our results demonstrate that the
      lipid core in LDL changes from a liquid crystalline to an oily state within
      fractions of seconds. This may, through the coupling to the protein structure of
      LDL, have important repercussions on current theories of the role of LDL in the
      pathogenesis of atherosclerosis.

PMID- 19114996
TI  - Mild electrical stimulation with heat shock ameliorates insulin resistance via
      enhanced insulin signaling.
AB  - Low-intensity electrical current (or mild electrical stimulation; MES) influences
      signal transduction and activates phosphatidylinositol-3 kinase (PI3K)/Akt
      pathway. Because insulin resistance is characterized by a marked reduction in
      insulin-stimulated PI3K-mediated activation of Akt, we asked whether MES could
      increase Akt phosphorylation and ameliorate insulin resistance. In addition, it
      was also previously reported that heat shock protein 72 (Hsp72) alleviates
      hyperglycemia. Thus, we applied MES in combination with heat shock (HS) to in
      vitro and in vivo models of insulin resistance. Here we show that 10-min
      treatment with MES at 5 V (0.1 ms pulse duration) together with HS at 42 degrees
      C increased the phosphorylation of insulin signaling molecules such as insulin
      receptor substrate (IRS) and Akt in HepG2 cells maintained in high-glucose
      medium. MES (12 V)+mild HS treatment of high fat-fed mice also increased the
      phosphorylation of insulin receptor beta subunit (IRbeta) and Akt in mice liver.
      In high fat-fed mice and db/db mice, MES+HS treatment for 10 min applied twice a
      week for 12-15 weeks significantly decreased fasting blood glucose and insulin
      levels and improved insulin sensitivity. The treated mice showed significantly
      lower weight of visceral and subcutaneous fat, a markedly improved fatty liver
      and decreased size of adipocytes. Our findings indicated that the combination of
      MES and HS alleviated insulin resistance and improved fat metabolism in diabetes
      mouse models, in part, by enhancing the insulin signaling pathway.

PMID- 19114997
TI  - Gamma-secretase-dependent and -independent effects of presenilin1 on beta
      catenin.Tcf-4 transcriptional activity.
AB  - Presenilin1 (PS1) is a component of the gamma-secretase complex mutated in cases
      of Familial Alzheimer's disease (FAD). PS1 is synthesized as a 50 kDa peptide
      subsequently processed to two 29 and 20 kDa subunits that remain associated.
      Processing of PS1 is inhibited by several mutations detected in FAD patients. PS1
      acts as negative modulator of beta-catenin.Tcf-4 transcriptional activity. In
      this article we show that in murine embryonic fibroblasts (MEFs) the mechanisms
      of action of the processed and non-processed forms of PS1 on beta-catenin.Tcf-4
      transcription are different. Whereas non-processed PS1 inhibits beta-catenin.Tcf
      4 activity through a mechanism independent of gamma-secretase and associated with
      the interaction of this protein with plakoglobin and Tcf-4, the effect of
      processed PS1 is prevented by gamma-secretase inhibitors, and requires its
      interaction with E- or N-cadherin and the generation of cytosolic terminal
      fragments of these two cadherins, which in turn destabilize the beta-catenin
      transcriptional cofactor CBP. Accordingly, the two forms of PS1 interact
      differently with E-cadherin or beta-catenin and plakoglobin: whereas processed
      PS1 binds E-cadherin with high affinity and beta-catenin or plakoglobin weakly,
      the non-processed form behaves inversely. Moreover, contrarily to processed PS1,
      that decreases the levels of c-fos RNA, non-processed PS1 inhibits the expression
      c-myc, a known target of beta-catenin.Tcf-4, and does not block the activity of
      other transcriptional factors requiring CBP. These results indicate that
      prevention of PS1 processing in FAD affects the mechanism of repression of the
      transcriptional activity dependent on beta-catenin.

PMID- 19114998
TI  - Akt regulates drug-induced cell death through Bcl-w downregulation.
AB  - Akt is a serine threonine kinase with a major role in transducing survival
      signals and regulating proteins involved in apoptosis. To find new interactors of
      Akt involved in cell survival, we performed a two-hybrid screening in yeast using
      human full-length Akt c-DNA as bait and a murine c-DNA library as prey. Among the
      80 clones obtained, two were identified as Bcl-w. Bcl-w is a member of the Bcl-2
      family that is essential for the regulation of cellular survival, and that is up
      regulated in different human tumors, such as gastric and colorectal carcinomas.
      Direct interaction of Bcl-w with Akt was confirmed by immunoprecipitation assays.
      Subsequently, we addressed the function of this interaction: by interfering with
      the activity or amount of Akt, we have demonstrated that Akt modulates the amount
      of Bcl-w protein. We have found that inhibition of Akt activity may promote
      apoptosis through the downregulation of Bcl-w protein and the consequential
      reduction in interaction of Bcl-w with pro-apoptotic members of the Bcl-2 family.
      Our data provide evidence that Bcl-w is a new member of the Akt pathway and that
      Akt may induce anti-apoptotic signals at least in part through the regulation of
      the amount and activity of Bcl-w.

PMID- 19114999
TI  - Differential RhoA dynamics in migratory and stationary cells measured by FRET and
      automated image analysis.
AB  - Genetically-encoded biosensors based on fluorescence resonance energy transfer
      (FRET) have been widely applied to study the spatiotemporal regulation of
      molecular activity in live cells with high resolution. The efficient and accurate
      quantification of the large amount of imaging data from these single-cell FRET
      measurements demands robust and automated data analysis. However, the nonlinear
      movement of live cells presents tremendous challenge for this task. Based on
      image registration of the single-cell movement, we have developed automated image
      analysis methods to track and quantify the FRET signals within user-defined
      subcellular regions. In addition, the subcellular pixels were classified
      according to their associated FRET signals and the dynamics of the clusters
      analyzed. The results revealed that the EGF-induced reduction of RhoA activity in
      migratory HeLa cells is significantly less than that in stationary cells.
      Furthermore, the RhoA activity is polarized in the migratory cells, with the
      gradient of polarity oriented toward the opposite direction of cell migration. In
      contrast, there is a lack of consistent preference in RhoA polarity among
      stationary cells. Therefore, our image analysis methods can provide powerful
      tools for high-throughput and systematic investigation of the spatiotemporal
      molecular activities in regulating functions of live cells with their shapes and
      positions continuously changing in time.

PMID- 19115000
TI  - Use of integrated malaria management reduces malaria in Kenya.
AB  - BACKGROUND: During an entomological survey in preparation for malaria control
      interventions in Mwea division, the number of malaria cases at the Kimbimbi sub
      district hospital was in a steady decline. The underlying factors for this
      reduction were unknown and needed to be identified before any malaria
      intervention tools were deployed in the area. We therefore set out to investigate
      the potential factors that could have contributed to the decline of malaria cases
      in the hospital by analyzing the malaria control knowledge, attitudes and
      practices (KAP) that the residents in Mwea applied in an integrated fashion, also
      known as integrated malaria management (IMM). METHODS: Integrated Malaria
      Management was assessed among community members of Mwea division, central Kenya
      using KAP survey. The KAP study evaluated community members' malaria disease
      management practices at the home and hospitals, personal protection measures used
      at the household level and malaria transmission prevention methods relating to
      vector control. Concurrently, we also passively examined the prevalence of
      malaria parasite infection via outpatient admission records at the major referral
      hospital in the area. In addition we studied the mosquito vector population
      dynamics, the malaria sporozoite infection status and entomological inoculation
      rates (EIR) over an 8 month period in 6 villages to determine the risk of malaria
      transmission in the entire division. RESULTS: A total of 389 households in Mwea
      division were interviewed in the KAP study while 90 houses were surveyed in the
      entomological study. Ninety eight percent of the households knew about malaria
      disease while approximately 70% of households knew its symptoms and methods to
      manage it. Ninety seven percent of the interviewed households went to a health
      center for malaria diagnosis and treatment. Similarly a higher proportion (81%)
      used anti-malarial medicines bought from local pharmacies. Almost 90% of
      households reported owning and using an insecticide treated bed net and 81%
      reported buying the nets within the last 5 years. The community also used
      mosquito reduction measures including, in order of preference, environmental
      management (35%), mosquito repellent and smoke (31%) insecticide canister sprays
      (11%), and window and door screens (6%). These methods used by the community
      comprise an integrated malaria management (IMM) package. Over the last 4 years
      prior to this study, the malaria cases in the community hospital reduced from
      about 40% in 2000 to less than 10% by 2004 and by the year 2007 malaria cases
      decreased to zero. In addition, a one time cross-sectional malaria parasite
      survey detected no Plasmodium infection in 300 primary school children in the
      area. Mosquito vector populations were variable in the six villages but were
      generally lower in villages that did not engage in irrigation activities. The
      malaria risk as estimated by EIR remained low and varied by village and proximity
      to irrigation areas. The average EIR in the area was estimated at 0.011
      infectious bites per person per day. CONCLUSIONS: The usage of a combination of
      malaria control tools in an integrated fashion by residents of Mwea division
      might have influenced the decreased malaria cases in the district hospital and in
      the school children. A vigorous campaign emphasizing IMM should be adopted and
      expanded in Mwea division and in other areas with different eco-epidemiological
      patterns of malaria transmission. With sustained implementation and support from
      community members integrated malaria management can reduce malaria significantly
      in affected communities in Africa.

PMID- 19115002
TI  - Neural representations of airflow in Drosophila mushroom body.
AB  - The Drosophila mushroom body (MB) is a higher olfactory center where olfactory
      and other sensory information are thought to be associated. However, how MB
      neurons of Drosophila respond to sensory stimuli other than odor is not known.
      Here, we characterized the responses of MB neurons to a change in airflow, a
      stimulus associated with odor perception. In vivo calcium imaging from MB neurons
      revealed surprisingly strong and dynamic responses to an airflow stimulus. This
      response was dependent on the movement of the 3(rd) antennal segment, suggesting
      that Johnston's organ may be detecting the airflow. The calyx, the input region
      of the MB, responded homogeneously to airflow on. However, in the output lobes of
      the MB, different types of MB neurons responded with different patterns of
      activity to airflow on and off. Furthermore, detailed spatial analysis of the
      responses revealed that even within a lobe that is composed of a single type of
      MB neuron, there are subdivisions that respond differently to airflow on and off.
      These subdivisions within a single lobe were organized in a stereotypic manner
      across flies. For the first time, we show that changes in airflow affect MB
      neurons significantly and these effects are spatially organized into divisions
      smaller than previously defined MB neuron types.

PMID- 19115001
TI  - In vitro and in vivo human herpesvirus 8 infection of placenta.
AB  - Herpesvirus infection of placenta may be harmful in pregnancy leading to
      disorders in fetal growth, premature delivery, miscarriage, or major congenital
      abnormalities. Although a correlation between human herpesvirus 8 (HHV-8)
      infection and abortion or low birth weight in children has been suggested, and
      rare cases of in utero or perinatal HHV-8 transmission have been documented, no
      direct evidence of HHV-8 infection of placenta has yet been reported. The aim of
      this study was to evaluate the in vitro and in vivo susceptibility of placental
      cells to HHV-8 infection. Short-term infection assays were performed on placental
      chorionic villi isolated from term placentae. Qualitative and quantitative HHV-8
      detection were performed by PCR and real-time PCR, and HHV-8 proteins were
      analyzed by immunohistochemistry. Term placenta samples from HHV-8-seropositive
      women were analyzed for the presence of HHV-8 DNA and antigens. In vitro infected
      histocultures showed increasing amounts of HHV-8 DNA in tissues and supernatants;
      cyto- and syncitiotrophoblasts, as well as endothelial cells, expressed latent
      and lytic viral antigens. Increased apoptotic phenomena were visualized by the
      terminal deoxynucleotidyl transferase-mediated deoxyuridine nick end-labeling
      method in infected histocultures. Ex vivo, HHV-8 DNA and a latent viral antigen
      were detected in placenta samples from HHV-8-seropositive women. These findings
      demonstrate that HHV-8, like other human herpesviruses, may infect placental
      cells in vitro and in vivo, thus providing evidence that this phenomenon might
      influence vertical transmission and pregnancy outcome in HHV-8-infected women.

PMID- 19115003
TI  - SERPINA3K prevents oxidative stress induced necrotic cell death by inhibiting
      calcium overload.
AB  - BACKGROUND: SERPINA3K, an extracellular serine proteinase inhibitor (serpin), has
      been shown to have decreased levels in the retinas of diabetic rats, which may
      contribute to diabetic retinopathy. The function of SERPINA3K in the retina has
      not been investigated. METHODOLOGY/PRINCIPAL FINDINGS: The present study
      identified a novel function of SERPINA3K, i.e. it protects retinal cells against
      oxidative stress-induced cell death including retinal neuronal cells and Muller
      cells. Flow-cytometry showed that the protective effect of SERPINA3K on Muller
      cells is via reducing oxidation-induced necrosis. Measurements of intracellular
      calcium concentration showed that SERPINA3K prevented the intracellular calcium
      overload induced by H(2)O(2). A similar protective effect was observed using a
      calcium chelator (BAPTA/AM). Further, SERPINA3K inhibited the phosphorylation of
      phospholipase C (PLC)-gamma1 induced by H(2)O(2). Likewise, a specific PLC
      inhibitor showed similar protective effects on Muller cells exposed to H(2)O(2).
      Furthermore, the protective effect of SERPINA3K was attenuated by a specific PLC
      activator (m-3M3FBS). Finally, in a binding assay, SERPINA3K displayed saturable
      and specific binding on Muller cells. CONCLUSION/SIGNIFICANCE: These results for
      the first time demonstrate that SERPINA3K is an endogenous serpin which protects
      cells from oxidative stress-induced cells death, and its protective effect is via
      blocking the calcium overload through the PLC pathway. The decreased retinal
      levels of SERPINA3K may represent a new pathogenic mechanism for the retinal
      Muller cell dysfunction and neuron loss in diabetes.

PMID- 19115005
TI  - Exploratory analysis of the copy number alterations in glioblastoma multiforme.
AB  - BACKGROUND: The Cancer Genome Atlas project (TCGA) has initiated the analysis of
      multiple samples of a variety of tumor types, starting with glioblastoma
      multiforme. The analytical methods encompass genomic and transcriptomic
      information, as well as demographic and clinical data about the sample donors.
      The data create the opportunity for a systematic screening of the components of
      the molecular machinery for features that may be associated with tumor formation.
      The wealth of existing mechanistic information about cancer cell biology provides
      a natural reference for the exploratory exercise. METHODOLOGY/PRINCIPAL FINDINGS:
      Glioblastoma multiforme DNA copy number data was generated by The Cancer Genome
      Atlas project for 167 patients using 227 aCGH experiments, and was analyzed to
      build a catalog of aberrant regions. Genome screening was performed using an
      information theory approach in order to quantify aberration as a deviation from a
      centrality without the bias of untested assumptions about its parametric nature.
      A novel Cancer Genome Browser software application was developed and is made
      public to provide a user-friendly graphical interface in which the reported
      results can be reproduced. The application source code and stand alone executable
      are available at (http://code.google.com/p/cancergenome) and
      (http://bioinformaticstation.org), respectively. CONCLUSIONS/SIGNIFICANCE: The
      most important known copy number alterations for glioblastoma were correctly
      recovered using entropy as a measure of aberration. Additional alterations were
      identified in different pathways, such as cell proliferation, cell junctions and
      neural development. Moreover, novel candidates for oncogenes and tumor
      suppressors were also detected. A detailed map of aberrant regions is provided.

PMID- 19115006
TI  - Rapid acoustic survey for biodiversity appraisal.
AB  - Biodiversity assessment remains one of the most difficult challenges encountered
      by ecologists and conservation biologists. This task is becoming even more urgent
      with the current increase of habitat loss. Many methods-from rapid biodiversity
      assessments (RBA) to all-taxa biodiversity inventories (ATBI)-have been developed
      for decades to estimate local species richness. However, these methods are costly
      and invasive. Several animals-birds, mammals, amphibians, fishes and arthropods
      produce sounds when moving, communicating or sensing their environment. Here we
      propose a new concept and method to describe biodiversity. We suggest to forego
      species or morphospecies identification used by ATBI and RBA respectively but
      rather to tackle the problem at another evolutionary unit, the community level.
      We also propose that a part of diversity can be estimated and compared through a
      rapid acoustic analysis of the sound produced by animal communities. We produced
      alpha and beta diversity indexes that we first tested with 540 simulated acoustic
      communities. The alpha index, which measures acoustic entropy, shows a
      logarithmic correlation with the number of species within the acoustic community.
      The beta index, which estimates both temporal and spectral dissimilarities, is
      linearly linked to the number of unshared species between acoustic communities.
      We then applied both indexes to two closely spaced Tanzanian dry lowland coastal
      forests. Indexes reveal for this small sample a lower acoustic diversity for the
      most disturbed forest and acoustic dissimilarities between the two forests
      suggest that degradation could have significantly decreased and modified
      community composition. Our results demonstrate for the first time that an
      indicator of biological diversity can be reliably obtained in a non-invasive way
      and with a limited sampling effort. This new approach may facilitate the
      appraisal of animal diversity at large spatial and temporal scales.

PMID- 19115004
TI  - Aging alters functionally human dermal papillary fibroblasts but not reticular
      fibroblasts: a new view of skin morphogenesis and aging.
AB  - Understanding the contribution of the dermis in skin aging is a key question,
      since this tissue is particularly important for skin integrity, and because its
      properties can affect the epidermis. Characteristics of matched pairs of dermal
      papillary and reticular fibroblasts (Fp and Fr) were investigated throughout
      aging, comparing morphology, secretion of cytokines, MMPs/TIMPs, growth
      potential, and interaction with epidermal keratinocytes. We observed that Fp
      populations were characterized by a higher proportion of small cells with low
      granularity and a higher growth potential than Fr populations. However, these
      differences became less marked with increasing age of donors. Aging was also
      associated with changes in the secretion activity of both Fp and Fr. Using a
      reconstructed skin model, we evidenced that Fp and Fr cells do not possess
      equivalent capacities to sustain keratinopoiesis. Comparing Fp and Fr from young
      donors, we noticed that dermal equivalents containing Fp were more potent to
      promote epidermal morphogenesis than those containing Fr. These data emphasize
      the complexity of dermal fibroblast biology and document the specific functional
      properties of Fp and Fr. Our results suggest a new model of skin aging in which
      marked alterations of Fp may affect the histological characteristics of skin.

PMID- 19115007
TI  - Transmission dynamics of Schistosoma japonicum in the lakes and marshlands of
      China.
AB  - BACKGROUND: Schistosoma japonicum is a major public health concern in China, with
      over one million people infected and another 40 million living in areas at risk
      of infection. Unlike the disease caused by S. mansoni and S. haematobium,
      schistosomiasis japonica is a zoonosis, involving a number of different mammalian
      species as reservoir hosts. As a result of a number of published reports from
      China, it has long been considered that bovines, particularly water buffaloes,
      play a major role in human S. japonicum transmission there, and a drug-based
      intervention study (1998-2003) around the Poyang Lake in Jiangxi Province
      provided proof of concept that water buffaloes are, indeed, major reservoirs of
      human infection in this setting. METHODS AND FINDINGS: In this study we
      incorporated recently obtained epidemiological information to model the steady
      state S. japonicum transmission as well as the impact of the removal of S.
      japonicum transmission attributable to water buffaloes on human infection rates
      across six different endemic scenarios within three villages in the Dongting
      (Hunan) and Poyang (Jiangxi) lakes of southern China. Similar results were
      obtained for all scenarios. Steady-state S. japonicum infection rates remained
      constant and human prevalence and incidence were predicted to fall considerably
      over time. The model showed that the contribution of S. japonicum water buffalo
      transmission to human infection ranged from 39.1% to 99.1% and predicted that the
      removal of water buffalo transmission would reduce parasite reproductive rates
      below 1. This indicates that without the contribution of water buffaloes, S.
      japonicum transmission is interrupted and unsustainable. These scenarios are
      generalizable to other endemic villages in the lake and marshland areas of China
      where a similar cycle of snail infection and infection/reinfection of humans and
      bovines occurs. CONCLUSIONS: Along with previous epidemiological data, our
      findings strongly support water buffaloes as an important component of the
      transmission cycle that affects humans in the lake and marshlands region of
      China, a feature which appears to differ from the situation prevalent in the
      Philippines where their contribution is less pronounced. Our conclusions
      underscore the rationale for removal, replacement or treatment of water
      buffaloes, and for the development and deployment of a transmission blocking
      buffalo vaccine against S. japonicum for this setting to achieve the goal of
      transmission control. The Chinese Government has recently commenced a new
      integrated national strategy to improve on existing approaches to control
      schistosomiasis in the lake and marshlands region by reducing bovines and humans
      as a source of S. japonicum infection to Oncomelania snails.

PMID- 19115009
TI  - Testing the goodness of supplementary feeding to enhance population viability in
      an endangered vulture.
AB  - BACKGROUND: Human-predator conflicts are directly or indirectly threatening many
      species with extinction. Thus, biologists are urged to find simple solutions to
      complex situations while avoiding unforeseen conservation outcomes. The provision
      of supplementary food at artificial feeding sites (AFS) is frequently used in the
      conservation of scavenger bird populations currently suffering from indirect
      poisoning, although no scientific studies on its effectiveness have been
      conducted. METHODOLOGY/PRINCIPAL FINDINGS: We used a long-term data set of 95
      individually marked birds from the largest European core of the endangered
      bearded vulture (Gypaetus barbatus) to test the long-term effects of specific AFS
      for bearded vultures on their survival rates (by CMR models) and population
      dynamics (by Monte Carlo simulations) in an area where fatalities derived from
      illegal poisoning and the use of other toxics like veterinary drugs have
      increased over the last several years. Our data support the positive relationship
      between the use of AFS and survival. However, contrary to theoretical predictions
      (e.g. high and more stable adult survival among long-lived species), the use of
      AFS increased only survival of pre-adults. Moreover, AFS buffered the effects of
      illegal poisoning on this age-class, while adult survival decreased over years.
      Our simulations predicted a maximum value of extinction probability over a time
      horizon of 50 years. Population projections run with survival rates expected in
      scenarios without poisoning predicted the situation of least conservation
      concern, while including only AFS can maintain a large floater surplus that may
      delay population decline but fails to reduce poisoning risk among adults.
      CONCLUSIONS/SIGNIFICANCE: Although AFS are not effective to save bearded vultures
      from an expected population decline, they delay population extinction and can be
      a useful tool for prolonging population viability while combating illegal and
      indirect poisoning. The eradication of different sources of poisoning is of top
      priority to ensure the long-term viability of this and many other species.

PMID- 19115008
TI  - SDF1 gene variation is associated with circulating SDF1alpha level and
      endothelial progenitor cell number: the Bruneck Study.
AB  - BACKGROUND: Stromal cell-derived factor-1 (SDF1) and its receptor CXC chemokine
      receptor 4 (CXCR4) play a critical role in progenitor cell homing, mobilization
      and differentiation. It would be interesting to assess the predictive value of
      SDF-1alpha level for EPC number, and to ascertain whether there is a relationship
      between SDF1 gene variation, plasma SDF-1alpha level, and the number and function
      of circulating EPCs. We also tested whether EPC number and function was related
      to CXCR4 gene variation. METHODOLOGY AND PRINCIPAL FINDINGS: We genotyped a
      cohort of individuals who participated in the Bruneck Study for single nucleotide
      polymorphisms (SNPs) in the SDF1 and CXCR4 genes, and measured blood SDF1alpha
      level as well as EPC number and function. SDF1alpha levels were correlated with
      age, gender, alcohol consumption, circulating reticulocyte numbers, and
      concentrations of matrix metalloproteinase-9, C-reactive protein, cystatin C,
      fibrinogen and homocytein. In blood samples taken in 2005, EPC number was
      inversely associated with SDF1alpha level (p<0.001). EPC number in 2005 was also
      inversely associated with SDF1alpha level in 2000 (p = 0.009), suggesting a
      predictive value of plasma SDF1alpha level for EPC number. There was an
      association between the SDF1 gene rs2297630 SNP A/A genotype, increased SDF1alpha
      level (p = 0.002) and lower EPC number (p = 0.006). CONCLUSIONS: Our data
      indicate that a SDF1 gene variation (rs2297630) has an influence on SDF1alpha
      level and circulating EPC number, and that plasma SDF1alpha level is a predictor
      of EPC number.

PMID- 19115010
TI  - Symptomatic acute hepatitis C in Egypt: diagnosis, spontaneous viral clearance,
      and delayed treatment with 12 weeks of pegylated interferon alfa-2a.
AB  - BACKGROUND AND OBJECTIVES: The aim of this study was to estimate the proportion
      of spontaneous viral clearance (SVC) after symptomatic acute hepatitis C and to
      evaluate the efficacy of 12 weeks of pegylated interferon alfa-2a in patients who
      did not clear the virus spontaneously. METHODS: Patients with symptomatic acute
      hepatitis C were recruited from two "fever hospitals" in Cairo, Egypt. Patients
      still viremic three months after the onset of symptoms were considered for
      treatment with 12 weeks of pegylated interferon alfa-2a (180 microg/week).
      RESULTS: Between May 2002 and February 2006, 2243 adult patients with acute
      hepatitis were enrolled in the study. The SVC rate among 117 patients with acute
      hepatitis C was 33.8% (95%CI [25.9%-43.2%]) at three months and 41.5% (95%CI
      [33.0%-51.2%]) at six months. The sustained virological response (SVR) rate among
      the 17 patients who started treatment 4-6 months after onset of symptoms was
      15/17 = 88.2% (95%CI [63.6%-98.5%]). CONCLUSION: Spontaneous viral clearance was
      high (41.5% six months after the onset of symptoms) in this population with
      symptomatic acute hepatitis C. Allowing time for spontaneous clearance should be
      considered before treatment is initiated for symptomatic acute hepatitis C.

PMID- 19115011
TI  - Brian: a simulator for spiking neural networks in python.
AB  - "Brian" is a new simulator for spiking neural networks, written in Python
      (http://brian. di.ens.fr). It is an intuitive and highly flexible tool for
      rapidly developing new models, especially networks of single-compartment neurons.
      In addition to using standard types of neuron models, users can define models by
      writing arbitrary differential equations in ordinary mathematical notation.
      Python scientific libraries can also be used for defining models and analysing
      data. Vectorisation techniques allow efficient simulations despite the overheads
      of an interpreted language. Brian will be especially valuable for working on non
      standard neuron models not easily covered by existing software, and as an
      alternative to using Matlab or C for simulations. With its easy and intuitive
      syntax, Brian is also very well suited for teaching computational neuroscience.

PMID- 19115012
TI  - Genetic variation stimulated by epigenetic modification.
AB  - Homologous recombination is essential for maintaining genomic integrity. A common
      repair mechanism, it uses a homologous or homeologous donor as a template for
      repair of a damaged target gene. Such repair must be regulated, both to identify
      appropriate donors for repair, and to avoid excess or inappropriate
      recombination. We show that modifications of donor chromatin structure can
      promote homology-directed repair. These experiments demonstrate that either the
      activator VP16 or the histone chaperone, HIRA, accelerated gene conversion
      approximately 10-fold when tethered within the donor array for Ig gene conversion
      in the chicken B cell line DT40. VP16 greatly increased levels of acetylated
      histones H3 and H4, while tethered HIRA did not affect histone acetylation, but
      caused an increase in local nucleosome density and levels of histone H3.3. Thus,
      epigenetic modification can stimulate genetic variation. The evidence that
      distinct activating modifications can promote similar functional outcomes
      suggests that a variety of chromatin changes may regulate homologous
      recombination, and that disregulation of epigenetic marks may have deleterious
      genetic consequences.

PMID- 19115013
TI  - Function and assembly of a chromatin-associated RNase P that is required for
      efficient transcription by RNA polymerase I.
AB  - BACKGROUND: Human RNase P has been initially described as a tRNA processing
      enzyme, consisting of H1 RNA and at least ten distinct protein subunits. Recent
      findings, however, indicate that this catalytic ribonucleoprotein is also
      required for transcription of small noncoding RNA genes by RNA polymerase III
      (Pol III). Notably, subunits of human RNase P are localized in the nucleolus,
      thus raising the possibility that this ribonucleoprotein complex is implicated in
      transcription of rRNA genes by Pol I. METHODOLOGY/PRINCIPAL FINDINGS: By using
      biochemical and reverse genetic means we show here that human RNase P is required
      for efficient transcription of rDNA by Pol I. Thus, inactivation of RNase P by
      targeting its protein subunits for destruction by RNA interference or its H1 RNA
      moiety for specific cleavage causes marked reduction in transcription of rDNA by
      Pol I. However, RNase P restores Pol I transcription in a defined reconstitution
      system. Nuclear run on assays reveal that inactivation of RNase P reduces the
      level of nascent transcription by Pol I, and more considerably that of Pol III.
      Moreover, RNase P copurifies and associates with components of Pol I and its
      transcription factors and binds to chromatin of the promoter and coding region of
      rDNA. Strikingly, RNase P detaches from transcriptionally inactive rDNA in
      mitosis and reassociates with it at G1 phase through a dynamic and stepwise
      assembly process that is correlated with renewal of transcription.
      CONCLUSIONS/SIGNIFICANCE: Our findings reveal that RNase P activates
      transcription of rDNA by Pol I through a novel assembly process and that this
      catalytic ribonucleoprotein determines the transcription output of Pol I and Pol
      III, two functionally coordinated transcription machineries.

PMID- 19115014
TI  - A recalibrated molecular clock and independent origins for the cholera pandemic
      clones.
AB  - Cholera, caused by Vibrio cholerae, erupted globally from South Asia in 7
      pandemics, but there were also local outbreaks between the 6(th) (1899-1923) and
      7(th) (1961-present) pandemics. All the above are serotype O1, whereas
      environmental or invertebrate isolates are antigenically diverse. The pre 7th
      pandemic isolates mentioned above, and other minor pathogenic clones, are related
      to the 7(th) pandemic clone, while the 6(th) pandemic clone is in the same
      lineage but more distantly related, and non-pathogenic isolates show no clonal
      structure. To understand the origins and relationships of the pandemic clones, we
      sequenced the genomes of a 1937 prepandemic strain and a 6(th) pandemic isolate,
      and compared them with the published 7(th) pandemic genome. We distinguished
      mutational and recombinational events, and allocated these and other events, to
      specific branches in the evolutionary tree. There were more mutational than
      recombinational events, but more genes, and 44 times more base pairs, changed by
      recombination. We used the mutational single-nucleotide polymorphisms and known
      isolation dates of the prepandemic and 7(th) pandemic isolates to estimate the
      mutation rate, and found it to be 100 fold higher than usually assumed. We then
      used this to estimate the divergence date of the 6(th) and 7(th) pandemic clones
      to be about 1880. While there is a large margin of error, this is far more
      realistic than the 10,000-50,000 years ago estimated using the usual assumptions.
      We conclude that the 2 pandemic clones gained pandemic potential independently,
      and overall there were 29 insertions or deletions of one or more genes. There
      were also substantial changes in the major integron, attributed to gain of
      individual cassettes including copying from within, or loss of blocks of
      cassettes. The approaches used open up new avenues for analysing the origin and
      history of other important pathogens.

PMID- 19115015
TI  - A survey of honey bee colony losses in the U.S., fall 2007 to spring 2008.
AB  - BACKGROUND: Honey bees are an essential component of modern agriculture. A
      recently recognized ailment, Colony Collapse Disorder (CCD), devastates colonies,
      leaving hives with a complete lack of bees, dead or alive. Up to now, estimates
      of honey bee population decline have not included losses occurring during the
      wintering period, thus underestimating actual colony mortality. Our survey
      quantifies the extent of colony losses in the United States over the winter of
      2007-2008. METHODOLOGY/PRINCIPAL FINDINGS: Surveys were conducted to quantify and
      identify management factors (e.g. operation size, hive migration) that contribute
      to high colony losses in general and CCD symptoms in particular. Over 19% of the
      country's estimated 2.44 million colonies were surveyed. A total loss of 35.8% of
      colonies was recorded; an increase of 11.4% compared to last year. Operations
      that pollinated almonds lost, on average, the same number of colonies as those
      that did not. The 37.9% of operations that reported having at least some of their
      colonies die with a complete lack of bees had a total loss of 40.8% of colonies
      compared to the 17.1% loss reported by beekeepers without this symptom. Large
      operations were more likely to have this symptom suggesting that a contagious
      condition may be a causal factor. Sixty percent of all colonies that were
      reported dead in this survey died without dead bees, and thus possibly suffered
      from CCD. In PA, losses varied with region, indicating that ambient temperature
      over winter may be an important factor. CONCLUSIONS/SIGNIFICANCE: Of utmost
      importance to understanding the recent losses and CCD is keeping track of losses
      over time and on a large geographic scale. Given that our surveys are
      representative of the losses across all beekeeping operations, between 0.75 and
      1.00 million honey bee colonies are estimated to have died in the United States
      over the winter of 2007-2008. This article is an extensive survey of U.S.
      beekeepers across the continent, serving as a reference for comparison with
      future losses as well as providing guidance to future hypothesis-driven research
      on the causes of colony mortality.

PMID- 19115016
TI  - RIG-I and dsRNA-induced IFNbeta activation.
AB  - Except for viruses that initiate RNA synthesis with a protein primer (e.g.,
      picornaviruses), most RNA viruses initiate RNA synthesis with an NTP, and at
      least some of their viral (ppp)RNAs remain unblocked during the infection.
      Consistent with this, most viruses require RIG-I to mount an innate immune
      response, whereas picornaviruses require mda-5. We have examined a SeV infection
      whose ability to induce interferon depends on the generation of capped dsRNA
      (without free 5' tri-phosphate ends), and found that this infection as well
      requires RIG-I and not mda-5. We also provide evidence that RIG-I interacts with
      poly-I/C in vivo, and that heteropolymeric dsRNA and poly-I/C interact directly
      with RIG-I in vitro, but in different ways; i.e., poly-I/C has the unique ability
      to stimulate the helicase ATPase of RIG-I variants which lack the C-terminal
      regulatory domain.

PMID- 19115017
TI  - The vestibular component in out-of-body experiences: a computational approach.
AB  - Neurological evidence suggests that disturbed vestibular processing may play a
      key role in triggering out-of-body experiences (OBEs). Little is known about the
      brain mechanisms during such pathological conditions, despite recent experimental
      evidence that the scientific study of such experiences may facilitate the
      development of neurobiological models of a crucial aspect of self-consciousness:
      embodied self-location. Here we apply Bayesian modeling to vestibular processing
      and show that OBEs and the reported illusory changes of self-location and
      translation can be explained as the result of a mislead Bayesian inference, in
      the sense that ambiguous bottom-up signals from the vestibular otholiths in the
      supine body position are integrated with a top-down prior for the upright body
      position, which we measure during natural head movements. Our findings have
      relevance for self-location and translation under normal conditions and suggest
      novel ways to induce and study experimentally both aspects of bodily self
      consciousness in healthy subjects.

PMID- 19115018
TI  - [Dual diagnosis: actual situation and future prospects].
AB  - The term 'dual diagnosis' refers to the co-occurrence of at least one substance
      use disorder with another psychiatric disorder in the same individual. These
      'dual' patients or patients with psychiatric comorbidity are common, and present
      greater severity from both the clinical and social perspectives than those
      subjects with only one type of disorder (addictive or other psychiatric illness).
      We present the current situation regarding dual diagnosis from epidemiological,
      clinical and therapeutic perspectives and we review the most important challenges
      for the future. Among the challenges for the future, we highlight: the need to
      improve the understanding of the nosological characterisation of the co
      occurrence of psychopathological symptoms and the use, intoxication and
      withdrawal from substances; the need for clinical screening instruments to detect
      dual diagnosis; the need to develop effective therapeutic strategies both
      pharmacological and psychological; the importance of providing integrated care to
      these patients by one therapeutic team within a single mental health and
      addiction network; and finally, the need to incorporate training on dual
      diagnosis for health professionals.

PMID- 19115019
TI  - [Responsible gambling: is it an alternative for prevention and treatment of
      pathological gambling?].
AB  - This paper deals with the new development of controlled gambling embedded in a
      harm-reduction context as a viable solution both for primary prevention at school
      and for treatment of some kinds of problematic gamblers. Pathological gambling
      significantly improves with psychological therapies, such as stimulus control and
      in vivo exposure with response prevention or cognitive interventions. In some
      cases psychopharmacological therapy may complement the benefits of treatment for
      pathological gambling when patients have comorbid depression or high impulsivity.
      However, in this mental disorder the goal of treatment (total abstinence or
      controlled gambling) is currently a controversial issue. Controlled gambling may
      be a therapeutic option for young gamblers or patients without severe dependence.
      Furthermore, controlled gambling may be a relevant issue for health education in
      schools, with a view to teaching teenagers how to cope with actual and virtual
      exposure to gambling. Likewise, the gambling industry and governments are
      involved in harm minimization initiatives. Thus, it is necessary to coordinate a
      program of research that includes the industry, science, and public
      representatives, based on cooperative research that will permit the introduction
      of controlled gambling within a global strategic framework. We discuss the
      relevance of this review for clinical practice and for future research, as well
      as the unsolved problems in this field.

PMID- 19115020
TI  - [Social values and addiction: applicability and psychometric properties of VAL-89
      questionnaire].
AB  - OBJECTIVE: To study the psychometric properties of the VAL-89 questionnaire and
      its possible use in addict individuals who ask for treatment. METHOD: Analysis of
      the psychometric properties of the questionnaire and its factorial structure,
      applying it to 792 individuals. 365 of them were substance users seeking
      treatment and 427 were general population. RESULTS: Reliability of the
      questionnaire is confirmed, although its factorial structure appears to be
      different from the original. In our study appear 12 factors, instead of the
      original 10. These factors are named: Power, Stimulation, Submission, Tradition,
      Spirituality, Self-Sufficience, Hedonism, Sociability, Universality,
      Convencionalism, Idealism and Self-Realization. These factors are distributed
      through several dimensions represented by four axis: individual-social, dominance
      equality, tradition-pleasure and great values-anomie. CONCLUSIONS: The VAL-89
      questionnaire seems to be a useful tool to explore which are the more appreciated
      social values, being of special interest to know which are specially selected by
      addict individuals.

PMID- 19115021
TI  - [An analysis of Spanish scientific productivity in substance abuse according to
      disciplinary collaboration].
AB  - OBJECTIVES: The analysis of productivity and disciplinary collaboration patterns
      for Spanish published scientific research in the field of Substance Abuse (2001
      2005). METHODOLOGY: From institutional affiliations we identified and quantified
      disciplinary participation in papers indexed in the IME/Indice Medico Espanol,
      ISOC/Indice Espanol de Ciencias Sociales y Humanidades, SCI-Expanded/Science
      Citation Index-Expanded and SSCI/Social Sciences Citation Index databases.
      RESULTS: A total of 31 disciplines and specialities were identified in ISOC, with
      8.6% of documents in collaboration between them; 55 medical specialities were
      identified in IME, with 10.89% of documents in collaboration between them; and 62
      specialities were identified in SCI-Expanded, with 41.68% of documents in
      collaboration between them. CONCLUSIONS: a) Substance Abuse, Psychology,
      Psychiatry, Epidemiology-Preventive Medicine and Public Health and Pharmacology
      are the disciplines and specialities that present the highest productivity. To
      these can be added, in papers published in foreign journals, specialities such as
      Biochemistry-Molecular Biology, Neurology and Neuroscience; b) Papers published
      in Spanish journals indexed in SCI-Expanded and in papers published in foreign
      journals present much higher collaboration indexes between disciplines and
      specialities; c) The main collaborations between specialities are those between
      Substance Abuse, Psychiatry and Psychology. To these can be added, in the case of
      journals indexed in SCI-Expanded, those between these specialities and
      Pharmacology, Neurology and Neuroscience.

PMID- 19115022
TI  - [What happens in a cocaine-dependent sample after 24 months of treatment?].
AB  - The evolution of people in treatment for cocaine dependence at public Drug Abuse
      Centers is a relevant topic in view of the notable increase in demand for such
      treatment in recent years. The aim of the present study was to analyze the
      evolution of people with cocaine dependence receiving treatment at public Drug
      Abuse Centers in Galicia (NW Spain), two years after the initial assessment for
      inclusion on the treatment program. The sample for the present study was 38
      participants who formed part of a larger initial sample (N = 115). The variables
      analyzed were: substance use, social adjustment on the O.T.I. scale, problems
      with the legal system and perceived psychological distress as assessed with the
      scales and indices of the SCL-90 R. The results indicate that, after two years of
      treatment, 78.9% of those in the sample located (26% of the initial sample) had
      not consumed cocaine in the month prior to assessment, and that there was a
      reduction in psychological distress. These results indicate a positive evolution
      after two years of the sample of people in treatment for cocaine dependence
      assessed in this study.

PMID- 19115023
TI  - [Reasons for not accepting a sexual liaison in nightlife recreational contexts
      according to gender and state of drunkenness].
AB  - Recent years have seen an increase in drunkenness among young people who go out
      at weekends, but there is limited information on the relationship between
      sexuality and drunkenness in these contexts. Here we analyze, in a sample of 440
      people aged 14 to 25 who frequent nightlife recreational contexts, who have had
      sexual relationships and who use some type of drug or alcohol, the reasons for
      not initiating a sexual liason, as a function of drunkenness and gender. The
      sampling method used was respondent-driven sampling. The results show that 63.3%
      admit that under the effects of alcohol or other drugs they have failed to take
      precautions in their sexual relations, the proportion of women not taking
      precautions being higher than that of men. The results referring to the reasons
      for not initiating a sexual liason are similar across genders and states of
      drunkenness. The only difference found is that women are more likely to reject
      sex when the prospective partner is inappropriate. A logistic regression analysis
      indicates that drunkenness is the most important variable in explaining the
      different sexual behaviors. We conclude that drunkenness is related to the
      failure to take precautions in sexual relations, the results being similar in men
      and women.

PMID- 19115024
TI  - [Attention and craving. Advances in its conceptualization and its implications
      for relapse prevention].
AB  - Irresistible compulsion to use, or craving, is one of the key symptoms of
      substance dependence syndrome, and of major relevance with regard to relapse in
      the abuse of alcohol or other drugs. In the present paper, the relationship
      between attention, attentional processes and the craving phenomenon is reviewed.
      The paper also explores the different elements of attention, and particularly the
      relevance of selective attention in craving and the initial stages of relapse.
      Those psychological strategies that have emerged as effective in the management
      of craving for substances are also reviewed, with particular emphasis on the
      cognitive-behavioral model of relapse and on relapse-prevention therapy. Finally,
      we discuss the characteristics of so-called attentional therapy, based on
      mindfulness, and its potential effectiveness in the management of addictive
      disorders in general and of craving in particular.

PMID- 19115025
TI  - [Descriptive study of alcohol detoxifications in an Internal Medicine Service].
AB  - Alcohol dependence is a chronic disease whose treatment begins with
      detoxification, followed by rehabilitation. We present a descriptive and
      retrospective study of 147 patients admitted to our unit during the period 2003
      2005. Median age was 46.07 years, with 77.6% men and 22.4% women. Admission
      diagnosis was alcohol withdrawal syndrome in 31 patients (21.1%) and programmed
      alcohol detoxification in 116 patients (78.9%). On the CIWA-Ar scale: mild
      withdrawal, 100 patients (68.5%), moderate, 35 patients (24%), severe, 11
      patients (7.5%). Mild group showed a statistically significantly lower proportion
      of hepatopathy, by comparison with the moderate and severe groups. Statistically
      significant differences were found between the mild and severe groups on
      comparing mean age, duration of stay, quantity of alcohol and parameters of
      chronic consumption (ferritine, fe, VCM, UBE, AST, bilirubin and Mg) for AST and
      bilirubin. There were 11 seizures: 4 patients from the programmed group, with
      mild withdrawal on the CIWA-Ar scale, and 7 patients with moderate-severe
      withdrawal. No relationship was found between patients intensity of withdrawal
      syndrome, age or sex. There was higher intensity on the CIWA-Ar score (moderate
      and severe) among patients who had already begun withdrawal syndrome, compared to
      those admitted on a planned detoxification programme. The CIWA-Ar is a useful
      tool for assessing withdrawal symptoms and risks of complication and for planning
      treatment. Clinical practice must provide patients with access to health
      resources for the appropriate treatment of their addiction, with standardized
      assistance during their stay in hospital.

PMID- 19115026
TI  - [Why girls smoke: a structural model of smoking intention].
AB  - Tobacco use among girls is increasing at an accelerating pace, with adverse
      effects for their own health and that of their potential offspring. In order to
      test, through structural equation modeling techniques, an explanatory model of
      smoking intention in young girls, we applied a validated instrument to 386 female
      students at state and private secondary schools. The model considered the effect
      of six protective and risk factors on smoking intention, as well as the
      relationship between them. These variables were obtained from a multiple
      regression analysis which included a total of 25. The results indicated that
      having friends who smoke cigarettes constitutes the main influence on smoking
      intention in young girls. Parents play a fundamental protective role, since, on
      supervising their daughters activities and prohibiting smoking at home, the girls
      smoking intention is decreased, presence of friends who smoke is controlled, and
      rebellious behavior is moderated, and this influences the girls beliefs about the
      benefits of smoking. Believing that tobacco is really addictive is also a
      protective cognitive factor for such girls. Proposals are discussed for applying
      the findings to prevention programs addressing smoking in young girls, and in
      which parents are included.

PMID- 19115027
TI  - Alcohol psychoses and all-cause mortality in Belarus.
AB  - BACKGROUND: The burden of alcohol-related problems in central and eastern Europe
      is the highest in the world. The level of alcohol consumption in Belarus is among
      the highest in the world, with an annual consumption rate estimated to be 14
      litres of pure alcohol per capita. The social, economic and political turmoil
      that Belarus has experiences in the years following the dissolution of the Soviet
      Union has been accompanied by a substantial rise in all-cause mortality. Although
      alcohol seems to be an important contributor to the burden of disease in the
      former Soviet republics, little systematic research has been undertaken on its
      impact on all-cause mortality in Belarus. AIMS: The aim of the present study was
      to address this particular deficit concerning the alcohol-total mortality
      relationship in Belarus by using aggregate-level data. METHOD: Trends in the all
      cause mortality and alcohol psychoses incidence rates (as a proxy for alcohol
      consumption) from 1970 to 2005 were analyzed employing ARIMA time series analysis
      in order to asses bivariate relationship between the two time series. RESULTS:
      The results of time series analysis suggest a close relationship between all
      cause mortality and alcohol psychoses rates at the aggregate level. CONCLUSIONS:
      This study replicates the previous findings that suggested close link between
      alcohol and mortality. The outcome of present study also supports the hypothesis
      that alcohol is a crucial factor of mortality crisis in Belarus. Therefore,
      alcohol control must be a key priority for Belorussian public health policy.

PMID- 19115028
TI  - Do tumor cavitation and sex in resected stage I non-small-cell lung cancer
      correlate with prognosis?
AB  - BACKGROUND: Multiple factors have been reported as affecting the prognosis, and
      they affect the therapeutic outcomes of stage I non-small-cell lung cancer
      (NSCLC) patients. Most studies focus on patients receiving combined-modality
      therapy, whereas there are few studies that focus on patients undergoing surgery
      alone. The aim of this study was to identify risk factors for disease relapse and
      unfavorable prognosis in stage I NSCLC patients treated with surgery alone.
      METHODS: A total of 315 stage I NSCLC patients who were treated with surgery
      alone as the definitive therapy were identified. Risk factors for disease relapse
      and unfavorable prognosis were estimated by univariate and multivariate analyses.
      RESULTS: Sex, tumor pathologic stage, and cavitating lung cancer were identified
      as independent risk factors for relapse and overall survival using the
      multivariate analysis. Sex, tumor pathologic stage, and cavitating lung cancer
      were identified as independent risk factors for early relapse, and sex and
      cavitating lung cancer were independent risk factors for late relapse.
      CONCLUSION: Tumor cavitation, pathologic stage IB, and being male are predictors
      of poor outcome for patients with stage I NSCLC who undergo resection.

PMID- 19115030
TI  - Pain management for unilateral orchidopexy in children: an effective regimen.
AB  - BACKGROUND: The reported high incidence of 30-60% postoperative pain after an
      elective day surgical orchidopexy is undesirable. We evaluated the efficacy of
      our analgesic regimen for unilateral orchidopexy in preschool children performed
      as a day surgical procedure. METHODS: Between January 2004 and December 2006, 247
      children (mean age: 3.3 +/- 1.6 years) underwent a unilateral orchidopexy as a
      day surgical procedure. They were prospectively analyzed for postoperative pain
      during a period of 48 h by using the Visual Analogue Scale (VAS). After
      standardized general anesthesia, all children had a 0.25% levo-bupivacaine
      hydrochloride ilio-inguinal block and a rectal diclofenac sodium suppository.
      Orchidopexy was performed through transverse inguinal and scrotal incisions. The
      wounds were infiltrated with 0.25% levo-bupivacaine hydrochloride at the end of
      the operation. Postoperatively acetaminophen and ibuprofen were given orally at
      regular intervals for 48 h. RESULTS: On first assessment in the recovery room,
      148 out of 247 (60%) patients were pain-free, and 99 of 247 (40%) patients had
      pain: VAS score ranged from 3 to 10. By 3 h, 27 (11%) had mild-to-moderate pain,
      with VAS scores between 3 and 7. All children were discharged home at 4 h with no
      pain. At home, 95% were pain-free at 10 h and 97% by 24 h, with a declining pain
      score. All children were pain-free at 32, 40, and 48 h. Pain scores were
      unrelated to the duration of surgery (r (s) = 0.54). CONCLUSION: Clinical
      effectiveness of our institution analgesic regime justifies the performance of
      unilateral orchidopexy as a day-case procedure.

PMID- 19115029
TI  - Basic principles and technologies for deciphering the genetic map of cancer.
AB  - The progress achieved in the field of genomics in recent years is leading
      medicine to adopt a personalized model in which the knowledge of individual DNA
      alterations will allow a targeted approach to cancer. Using pancreatic cancer as
      a model, we discuss herein the fundamentals that need to be considered for the
      high throughput and global identification of mutations. These include patient
      related issues, sample collection, DNA isolation, gene selection, primer design,
      and sequencing techniques. We also describe the possible applications of the
      discovery of DNA changes to the approach of this disease and cite preliminary
      efforts where the knowledge has been translated into the clinical or preclinical
      setting.

PMID- 19115031
TI  - Laparoscopy-assisted donor right hepatectomy using a hand port system preserving
      the middle hepatic vein branches.
AB  - BACKGROUND: This report reviews our experience with a modified right hepatectomy
      (MRH) using laparoscopic or laparoscopy-assisted techniques preserving the middle
      hepatic vein (MHV) branches in living donor liver transplantation. METHODS: Nine
      female donors (17-36 years) underwent a laparoscopic MRH under pneumoperitoneum
      (L-MRH; n = 2) or a laparoscopy-assisted MRH (LA-MRH; n = 7) with a hand port
      device. The donors for this minimally invasive surgery were volunteers with the
      willingness to undergo laparoscopic surgery and recipients who were not in urgent
      need of transplantation. Mobilization of the right liver was performed under
      pneumoperitoneum in all cases. Hilar dissection and parenchymal transection were
      performed under pneumoperitonuem (n = 2) or with a mini-laparotomy incision (n =
      7) using an ultrasonic aspirator without the Pringle maneuver. The major MHV
      branches (>5 mm) were preserved using Hem-o-lock clips. The graft was extracted
      through the site of the hand port device or the mini-laparotomy. On the back
      table, the MHV branches were reconstructed with an artificial vascular graft.
      RESULTS: There were no open conversions, and the graft was transplanted without
      any problem in every case. The operative time for the donors was 765 min and 898
      min in the L-MRH patients, and it ranged from 310 to 575 min for the laparoscopy
      assisted surgery. None of the donors required transfusion or reoperation; they
      were discharged on postoperative day 8-14 with normal liver function. A major
      complication occurred in one donor; fluid collection along the liver resection
      margin with fever was treated and resolved after percutaneous drainage.
      CONCLUSIONS: A right hepatectomy preserving the MHV or its branches by minimally
      invasive techniques including total laparoscopic surgery was technically
      feasible. However, further refinements of the procedure are required prior to
      wide clinical application.

PMID- 19115033
TI  - The complete nucleotide sequence of potato virus T.
AB  - Potato virus T (PVT), a member of an unassigned species in the family
      Flexiviridae, has a genome 6,539 nt in size with three ORFs coding for
      replication-associated proteins (185 kDa, ORF 1), movement protein (40 kDa, ORF
      2) and coat protein (24 kDa, ORF 3), respectively. PVT differs from the type
      members of all genera of the family Flexiviridae with a 30K-type movement protein
      and is phylogenetically distant from all of these viruses, least so from
      grapevine virus A (GVA, genus Vitivirus), with which it groups in all trees. The
      viral genome resembles that of trichoviruses but is smaller and does not contain
      the 3' terminal fourth ORF found in some members of this genus. PTV may represent
      a new genus of plant viruses for which the provisional name of Andesvirus is
      proposed.

PMID- 19115032
TI  - HSV immune complex (HSV-IgG: IC) and HSV-DNA elicit the production of angiogenic
      factor VEGF and MMP-9.
AB  - Angiogenesis and inflammatory mediators are critical pathogenic factors in
      herpetic stromal keratitis (HSK). Since disease progresses without infectious
      virus, HSV-DNA and HSV-IgG complexes (HSV-IC) may contribute to HSK by triggering
      these factors. Production of VEGF and MMP-9 was studied in vitro using corneal
      epithelial cells (HCE), fibroblasts (HCRF) and macrophages (THP-1). VEGF was
      elevated in HCRF and THP-1 following treatment with HSV-DNA and HSV-IC. MMP-9 was
      elevated in THP-1 but not in corneal cells. When anti-HSV-IgG(Fab')2 complexes
      stimulated THP-1, MMP-9 was reduced to control levels. Pretreatment of THP-1 with
      anti-TLR-2 and -3 inhibited MMP-9 production. Thus, HSV-IC may stimulate THP-1
      through the Fc receptor and TLRs. Proinflammatory cytokines (IL-1b, IL-6, and TNF
      alpha) increased VEGF and MMP-9 in corneal cells and macrophages. These studies
      indicate that the continued presence of HSV-DNA and HSV-IC contribute to
      angiogenesis and inflammation in HSK. Thus, cytokines and TLRs may be potential
      targets for intervention.

PMID- 19115034
TI  - Complete genome analysis and immunodetection of a member of a novel virus species
      belonging to the genus Ampelovirus.
AB  - A new grapevine leafroll-associated virus isolate (GLRaV-Pr) from Greek
      grapevines was recently reported. This virus, along with the genetically related
      GLRaV-4, -5, -6 and -9, form a separate diverse lineage within the genus
      Ampelovirus. In this paper, the complete nucleotide sequence of GLRaV-Pr was
      determined, making it the first fully sequenced virus of this lineage. Its genome
      is 13,696 nt long and contains seven open reading frames, which potentially
      encode a 253-kDa polyprotein containing papain-like protease, methyltransferase,
      AlkB and helicase domains, a 58.2-kDa RNA-dependent RNA polymerase, a 5.2-kDa
      hydrophobic protein, a 58.5-kDa heat shock 70 protein homologue, a 60-kDa
      protein, a 30-kDa coat protein (CP) and a 23-kDa protein. A virus-specific
      antibody was raised against the recombinant CP of GLRaV-Pr and was applied in
      western blot analysis. The genomic, serological and phylogenetic data reported
      here confirm that GLRaV-Pr is a member of a distinct Ampelovirus species.
      Comparisons of GLRaV-Pr with the only available genetically related, fully
      sequenced virus, PMWaV-1, PBNSPaV and the partially sequenced GLRaV-9 revealed
      that this lineage, including GLRaV-4, -5, -6, -9 and -De, exhibits a high
      uniformity of genome organization and includes the smallest and simplest viruses
      within the family Closteroviridae.

PMID- 19115035
TI  - Characterization of Halanaerobaculum tunisiense gen. nov., sp. nov., a new
      halophilic fermentative, strictly anaerobic bacterium isolated from a hypersaline
      lake in Tunisia.
AB  - A new halophilic anaerobe was isolated from the hypersaline surface sediments of
      El-Djerid Chott, Tunisia. The isolate, designated as strain 6SANG, grew at NaCl
      concentrations ranging from 14 to 30%, with an optimum at 20-22%. Strain 6SANG
      was a non-spore-forming, non-motile, rod-shaped bacterium, appearing singly, in
      pairs, or occasionally as long chains (0.7-1 x 4-13 microm) and showed a Gram
      negative-like cell wall pattern. It grew optimally at pH values between 7.2 and
      7.4, but had a very broad pH range for growth (5.9-8.4). Optimum temperature for
      growth was 42 degrees C (range 30-50 degrees C). Strain 6SANG required yeast
      extract for growth on sugars. Glucose, sucrose, galactose, mannose, maltose,
      cellobiose, pyruvate, and starch were fermented. The end products from glucose
      fermentation were acetate, butyrate, lactate, H(2), and CO(2). The G + C ratio of
      the DNA was 34.3 mol%. Strain 6SANG exhibited 16S rRNA gene sequence similarity
      values of 91-92% with members of the genus Halobacteroides, H. halobius being its
      closest phylogenetic relative. Based on phenotypic and phylogenetic
      characteristics, we propose that this bacterium be classified as a novel species
      of a novel genus, Halanaerobaculum tunisiense gen. nov., sp. nov. The type strain
      is 6SANG(T) (=DSM 19997(T)=JCM 15060(T)).

PMID- 19115036
TI  - Molecular characterization of the recombinant iron-containing alcohol
      dehydrogenase from the hyperthermophilic Archaeon, Thermococcus strain ES1.
AB  - The gene encoding a thermostable iron-containing alcohol dehydrogenase from
      Thermococcus Strain ES1 (ES1 ADH) was cloned, sequenced and expressed in
      Escherichia coli. The recombinant and native ES1 ADHs were purified using
      multistep column chromatography under anaerobic conditions. Both enzymes appeared
      to be homotetramers with a subunit size of 45+/-1 kDa as revealed by SDS-PAGE,
      which was close to the calculated value (44.8 kDa). The recombinant ADH contained
      1.0+/-0.1 g-atom iron per subunit. Both enzymes were sensitive to oxygen with a
      half-life upon exposure to air of about 4 min. The recombinant enzyme exhibited a
      specific activity of 105+/-2 U mg(-1), which was very similar to that of the
      native enzyme (110+/-3 U mg(-1)). The optimal pH-values for both enzymes for
      ethanol oxidation and acetaldehyde reduction were 10.4 and 7.0, respectively.
      Both enzymes also showed similar temperature-dependent activities, and catalyzed
      the oxidation of primary alcohols, but there was no activity towards methanol and
      secondary alcohols. Kinetic parameters of the enzymes showed lower K (m)-values
      for acetaldehyde and NADPH and higher K (m)-values for ethanol and NADP(+). It is
      concluded that the gene encoding ES1 ADH was expressed successfully in E. coli.
      This is the first report of a fully active recombinant version of an iron
      containing ADH from a hyperthermophile.

PMID- 19115037
TI  - ApoE phenotype is associated with inflammatory markers in middle-aged subjects.
AB  - OBJECTIVES: Apolipoprotein (apo) E phenotype has been associated with
      inflammation markers. The determinants of these associations and the relationship
      between novel inflammation marker, resistin, and apoE phenotype are studied here.
      METHODS AND RESULTS: Middle-aged subjects of the population- based cohort (n =
      526) of the OPERA- study were studied. Intima-media thickness (IMT) was measured
      with carotid ultrasound. The results suggest that, apoE phenotype was a
      significant independent predictive factor for resistin (p < 0.01) and hsCRP (p <
      0.01) levels. The association of ApoE phenotype with hsCRP was seen among the
      subjects with the normal renal function (p = 0.005). ApoE4 was associated (p <
      0.01) with the lowest hsCRP in the lowest IMT quartile while it's relation with
      the highest resistin levels was evident in the highest IMT quartile. CONCLUSIONS:
      ApoE phenotype is an independent determinant of plasma resistin and hsCRP levels.
      The extent of atherosclerosis and renal function seem to modify the effects of
      apoE phenotype on inflammatory parameters.

PMID- 19115038
TI  - Screening of mimetic peptides for CD14 binding site with LBP and antiendotoxin
      activity of mimetic peptide in vivo and in vitro.
AB  - OBJECTIVE AND DESIGN: The study was aimed at screening out the mimetic peptides
      from the binding site of lipopolysaccharide binding protein and CD 14, and then
      observing if the mimetic peptide will inhibit in vitro LPS-induced inflammatory
      reaction and function as an anti-endotoxin in the model of LPS-induced acute lung
      injury. MATERIAL AND METHODS: Human monocytic cell line (U937) was used in vitro.
      Thirty three-month-old SD rats were used. Phage display peptide library was
      adapted to screen mimetic peptide sequences. TREATMENT: U937 cells were exposed
      to treatment with LPS and rhLBP and then were incubated with MP12 at three
      different concentrations after they were induced and differentiated by PMA. LPS
      intravenous injection was used to establish a model of rat acute lung injury
      which was later treated with intravenous injection of MP12. RESULTS: We
      successfully obtained the mimetic peptide of lipopolysaccharide-binding protein
      and CD 14 binding site, the gene sequence of which is FHRWPTWPLPSP (MP12). MP12
      can markedly inhibit LPS induced TNF-alpha expression. MP12 can evidently
      increase PaO(2) of rats with acute lung injury and also increase the survival
      rate of these rats. CONCLUSIONS: MP12 (FHRWPTWPLPSP) has the same function as
      mimetic of lipopolysaccharide-binding protein and CD 14 binding site. The
      application of MP12, both in vitro and in vivo, confers the biological activity
      required to antagonise LBP/CD14 and block LPS inflammatory signals, and it can
      markedly enhance PaO(2) of rats suffering from acute lung injury and also enhance
      their survival rate.

PMID- 19115039
TI  - Characterisation of nicotine receptors on human peripheral blood mononuclear
      cells (PBMC).
AB  - AIM AND OBJECTIVE: The aim of the work was to characterise the nAChRs on human
      PBMC. METHOD: PBMC were isolated from human blood buffy coats provided by the
      blood transfusion service and were used for radioligand binding studies with
      [(3)H]-nicotine. RT-PCR experiments were used to determine nAChR subunit
      expression while immunoblotting experiments were used to confirm that nAChR
      subunits identified by RT-PCR were translated into protein. RESULTS: Binding
      studies suggested the presence of one binding site for (-)- nicotine on human
      peripheral blood lymphocytes. Competition studies showed that only (-)- nicotine,
      epibatidine and alpha-bungarotoxin, displaced radiolabelled nicotine from cells.
      RT-PCR studies demonstrated mRNA for alpha4, alpha5, alpha7, beta1 and beta2
      nAChRs subunits in PBMC. Expression of mRNA for the a5 subunit of nAChR was
      observed in all lymphocyte samples tested. In contrast, the expression pattern of
      mRNAs for alpha4, alpha7, beta1, and beta2 mRNAs subunits of nAChRs, varied
      between samples. Western blot analysis showed that protein for alpha4, alpha5,
      and alpha7 and beta2 nAChR subunits was expressed in most, but not all of the
      PBMC samples tested but some of the bands obtained were faint. CONCLUSION: The
      results obtained suggest that human PBMC contain nAChRs containing alpha4beta2,
      alpha4beta2alpha5, and/or alpha7 subunits.

PMID- 19115041
TI  - Potentiation by cigarette smoke of macrophage function against Leishmania
      donovani infection.
AB  - OBJECTIVE: Cigarette smoke is able to induce the generation of reactive oxygen
      species and pro-inflammatory cytokines, which are mediators of macrophage
      function and therefore, we have investigated the ability of cigarette smoke to
      activate Leishmania donovani infected peritoneal macrophage. MATERIALS AND
      METHODS: Cultured peritoneal macrophages were either left untreated or treated
      with aqueous cigarette smoke extract prior to L. donovani infection. Parasite
      burden was assessed by giemsa staining. The level of intracellular reactive
      oxygen species was determined by FACS analysis. PCR was performed to analyze mRNA
      levels of cytokines. NF- kappaB activity was assessed by EMSA and reporter assay.
      RESULTS: A pre-treatment with cigarette smoke extract (CSE) causes a decrease in
      parasite burden, an increase in intracellular ROS level, up-regulation of pro
      inflammatory cytokines, reduced expression of immuno-suppressive cytokine and
      boosting of NF-kappaB activity in L. donovani-infected macrophage. CONCLUSION:
      Low concentration of cigarette smoke extract (CSE) counteracts L. donovani
      infection-mediated suppression of macrophage function without affecting host cell
      viability. This study reveals a new role of cigarette smoke extract (CSE) as an
      activator of macrophage function.

PMID- 19115040
TI  - Activation by C5a of endothelial cell caspase 8 and cFLIP.
AB  - OBJECTIVES AND DESIGN: In this study, we examine the relationship between C5a and
      activation of cysteine aspartic acid protease 8 (caspase 8) in human umbilical
      vein endothelial cells (HUVEC). MATERIALS OR SUBJECTS: Primary cultures of HUVEC
      were used. TREATMENTS: Recombinant human C5a (50 ng/ml) was used in the presence
      or absence of 10 microg/ml cycloheximide (CHX). METHODS: HUVEC were treated with
      C5a alone and in the presence of CHX, then monitored for cell viability, poly-
      ADP-ribose 1 (PARP-1) and caspase 8 activities. Gene and protein expressions were
      assessed for caspase 8 and the caspase 8 homologue, FLICE -inhibitory protein
      (cFLIP). RESULTS: We found a 43.1 +/- 6.9 percent reduction in viability of HUVEC
      stimulated for 18 h with 50 ng/ml C5a in the presence of 10 microg/ml CHX (p <
      0.05). In contrast, the cell viability of cells stimulated for 18 h with 50 ng/ml
      C5a or 10 microg/ml CHX alone was not significantly different compared to the non
      stimulated control. Treatment of HUVEC with C5a induced an increase in caspase 8
      activity but did not significantly affect cFLIP levels. CONCLUSIONS: These data
      suggest caspase 8 activation induced by C5a leads to cell death if protein
      synthesis of antiapoptotic protein(s) is blocked.

PMID- 19115042
TI  - Cytokine induction by a linear 1,3-glucan, curdlan-oligo, in mouse leukocytes in
      vitro.
AB  - OBJECTIVE: Curdlan, an extracellular bacterial polysaccharide, is a linear beta
      1,3-glucan. Previously, we developed Curdlan-oligo (CRDO). We investigated its
      effect on the production of cytokines in leukocytes from mice, and compared its
      activity with that of SCG, a 6-branched 1,3-beta-glucan. METHODS: Splenocytes
      from DBA/2 mice were cultured with CRDO or SCG (0, 1, 10 or 100 microg/ml) in
      vitro, and then the supernatants were collected to measure cytokines. Bone marrow
      derived dendritic cells (BMDCs) were cultured with CRDO (0, 1, 10 or 100 ng/ml)
      in vitro, and then the supernatant was collected to measure cytokines. RESULTS:
      SCG stimulated splenocytes in DBA/2 mice to produce GM-CSF, IFN-gamma and TNF
      alpha. CRDO induced production of GM-CSF and IFN-gamma, but not TNF-alpha. The
      amounts of GM-CSF and IFN-gamma were small compared with those produced in
      response to SCG. The effect of SCG on TNF-alpha production was partially
      inhibited by CRDO. In bone marrow-derived dendritic cells, CRDO induced
      production of TNF-alpha and IL-6. CONCLUSION: Taken together, these results
      suggest that CRDO stimulated mouse leukocytes to induce the production of
      cytokines, and the mechanism of the effect of CRDO on leukocytes is different
      from that of SCG.

PMID- 19115043
TI  - An efficient protocol for the complete incorporation of methyl-protonated alanine
      in perdeuterated protein.
AB  - A strategy for the introduction of ((1)H,(13)C-methyl)-alanine into perdeuterated
      proteins is described. Specific protonation of alanine methyl groups to a level
      of 95% can be achieved by overexpressing proteins in M9/D(2)O based bacterial
      growth medium supplemented with 800 mg/l of 2-[(2)H], 3-[(13)C] L: -alanine.
      However, though simple, this approach results in undesired, non-specific
      background labeling due to isotope scrambling via different amino acid metabolic
      pathways. Following a careful analysis of known metabolic pathways we found that
      co-addition of perdeuterated forms of alpha-ketoisovalerate-d(7), succinate-d(4)
      and L: -isoleucine-d(10) with labeled L: -alanine, reduces undesired background
      labeling to <1%. When combined with recently developed methyl TROSY experiments,
      this methyl-specific labeling protocol permits the acquisition of excellent
      quality correlation spectra of alanine methyl groups in high molecular weight
      proteins. Our cost effective strategy offers a significant enhancement in the
      level of incorporation of methyl-labeled alanine in overexpressed proteins over
      previously reported methods.

PMID- 19115044
TI  - Genome-wide analysis of gene expression in soybean shoot apical meristem.
AB  - The shoot apical meristem (SAM) contains undifferentiated stem cells that are
      responsible for the initiation of above-ground organs. The nature of genetic
      programs and the regulatory networks underlying SAM function in a major legume
      crop, soybean was investigated here. We used soybean GeneChip (containing 37,744
      probe sets) to examine the transcript profiles associated with micro-dissected,
      actively growing SAMs or growth arrested axillary meristems (AMs) experiencing
      apical dominance, in comparison to that of non-meristem (NM) tissue. A total of
      1,090 and 1,523 transcripts were identified to be significantly up- or down
      regulated in the SAM in comparison to the NM. RT-PCR and in situ hybridization
      analysis were also carried out to verify the experimental approach. The resulting
      gene expression profiles point to the combinatorial role of diverse regulatory
      pathways including those associated with cell division and proliferation,
      epigenetic regulation, auxin-mediated responses and microRNA regulation in
      meristem function. In situ hybridization analysis on selected transcripts has
      implicated their roles in SAM maintenance and the establishment of organ
      polarity. We also identified a gene, ANGUSITFOLIA3 that could potentially serve
      as a novel marker for differentiating cells in the meristem. Computational
      analysis on the promoter regions of Arabidopsis thaliana orthologs of genes with
      high expression in the soybean SAM revealed a conserved over-representation of
      three cis-acting regulatory motifs. Our data show that plant meristems possess a
      unique transcriptional profile, with shared "molecular signatures" in apical and
      axillary meristems providing a rich source of novel target genes for further
      studies into a fundamental process that impacts plant growth and crop
      productivity.

PMID- 19115045
TI  - The Arabidopsis DNA mismatch repair gene PMS1 restricts somatic recombination
      between homeologous sequences.
AB  - The eukaryotic DNA mismatch repair (MMR) system contributes to maintaining the
      fidelity of genetic information by correcting replication errors and preventing
      illegitimate recombination events. This study aimed to examine the function(s) of
      the Arabidopsis thaliana PMS1 gene (AtPMS1), one of three homologs of the
      bacterial MutL gene in plants. Two independent mutant alleles (Atpms1-1 and
      Atpms1-2) were obtained and one of these (Atpms1-1) was studied in detail. The
      mutant exhibited a reduction in seed set and a bias against the transmission of
      the mutant allele. Somatic recombination, both homologous and homeologous, was
      examined using a set of reporter constructs. Homologous recombination remained
      unchanged in the mutant while homeologous recombination was between 1.7- and 4.8
      fold higher than in the wild type. This increase in homeologous recombination
      frequency was not correlated with the degree of sequence divergence. In RNAi
      lines, a range of increases in homeologous recombination were observed with two
      lines showing a 3.3-fold and a 3.6-fold increase. These results indicate that the
      AtPMS1 gene contributes to an antirecombination activity aimed at restricting
      recombination between diverged sequences.

PMID- 19115046
TI  - Back to square one: what do we know about the functions of muscle LIM protein in
      the heart?
AB  - Muscle LIM Protein (MLP) is small, just 198 amino acid long protein, which is
      specifically expressed in slow skeletal muscle and cardiac tissues. This article
      will focus on the cardiac functions of MLP: the current knowledge about
      localisation data, binding partners and animal models for the protein will be
      summarised, and the role of MLP in maintaining a healthy heart be discussed. This
      review will furthermore attempt to identify gaps in our knowledge-and hence
      future research potential-with a special focus on MLP's role in cardiac mechano
      signalling.

PMID- 19115047
TI  - Multiplicity of experimental approaches to therapy for genetic muscle diseases
      and necessity for population screening.
AB  - Currently a multiplicity of experimental approaches to therapy for genetic muscle
      diseases is being investigated. These include replacement of the missing gene,
      manipulation of the gene message, repair of the mutation, upregulation of an
      alternative gene and pharmacological interventions targeting a number of systems.
      A number of these approaches are in current clinical trials. There is
      considerable anticipation that perhaps more than one of the approaches will
      finally prove of clinical benefit, but there are many voices of caution. No
      matter which approaches might ultimately prove effective, there is a consensus
      that for most benefit to the patients it will be necessary to start treatment as
      early as possible. A consensus is also developing that the only way to do this is
      to implement population-based newborn screening to identify affected children
      shortly after birth. Population-based newborn screening is currently practised in
      very few places in the world and it brings with it implications for prevention
      rather than cure of genetic muscle diseases.

PMID- 19115048
TI  - Regulation of fast skeletal muscle activity by SERCA1 vicinal-cysteines.
AB  - During prolonged skeletal muscle contractions free radicals are produced that may
      lead to fatigue. Vicinal cysteines, known as a Vicinal-thiol groups react
      preferentially among them depending on redox potential. Therefore, we examined
      the role of VT groups on the activity and conformational changes of sarcoplasmic
      reticulum (SR) Ca(2+)-ATPase (SERCA1) from rabbit skeletal muscle isolated SR, by
      selective oxidation-reduction of VT-groups. After Ca(2+) is released from the SR
      to start contraction, SERCA1 pumps this cytosolic Ca(2+) back to the SR leading
      to muscle relaxation. Phenylarsine oxide (PAO) reacts selectively with VT
      proteins forming dithioarsines, which are stable but exchanges rapidly with 2,3
      dimercaptopropanol (BAL). When 0.1 mM PAO is added to isolated SR, 60 and 67%
      inhibition of SERCA1 hydrolytic and Ca(2+) uptake activities, respectively is
      observed. ATPase activity was fully reversible with 1 mM BAL. The SERCA1 thermal
      inactivation determined from isolated SR from muscle at rest showed a single
      transition for inactivation (T(i)) at 49 +/- 1.12 degrees C. In the presence of
      0.1 mM PAO, SERCA1 shows two transitions at T(i) 34 +/-0.9 degrees C and at 27 +/
      1.2 degrees C. The thermal denaturation profile of SERCA1 from muscle at rest,
      showed two transitions at T(m) = 51.5 +/-1.3 degrees C and 63 +/-1.02 degrees C
      related to nucleotide and Ca(2+) binding domains, respectively. Whereas isolated
      SR obtained after a protocol of tetanic stimulation to produce muscle fatigue,
      showed three transitions in the SERCA1 denaturation profile similar to the effect
      of PAO, addition of 1 mM BAL reverted the effect of fatigue on SERCA1
      denaturation profile. These results indicate a mechanism relating VT group's
      oxidation to muscle fatigue.

PMID- 19115049
TI  - Pathological defects in congenital myopathies.
AB  - Congenital myopathies are a molecularly, pathologically and clinically
      heterogenous group of disorders defined by hypotonia and muscle weakness, that
      usually present at birth or early childhood, in association with a characteristic
      morphological defect. The most common morphological defects are nemaline rods,
      cores of varying size, central nuclei, and type I fibre hypotrophy, with or
      without an additional abnormality. The defective genes responsible for many of
      the congenital myopathies are known, but there is considerable clinico
      pathological overlap. In particular, defects in more than one gene are associated
      with the presence of the same pathological feature, while defects in the same
      gene can result in more than one pathological feature. Understanding the
      complexities of these spectra is paramount to the elucidation of pathogenesis,
      and to the development of therapies.

PMID- 19115050
TI  - Acyl-CoA synthetases: fatty acid uptake and metabolic channeling.
AB  - The molecular mechanism of fatty acid uptake and utilization is of high medical
      relevance for the treatment of obesity, diabetes, and cardiovascular disease.
      Neuronal processes, hormones, and transcription factors are master regulators of
      these essential processes while their fine-tuning is achieved by modulating the
      activity and amount of enzymes. Proteins involved in fatty acid uptake and
      metabolism are important pharmaceutical targets. Only basic research on these
      molecules will lead to new strategies for therapy. Conceptionally, the
      intracellular utilization of long chain fatty acids may be subdivided into three
      steps: uptake across the plasma membrane, activation by esterification with
      coenzyme A, and subsequent metabolism. Long chain acyl-CoA synthetases (ACSLs)
      activate fatty acids for intracellular metabolism but are also involved in the
      regulation of uptake. The predominant pathways for fatty acids are their storage,
      membrane biosynthesis, and conversion to energy. How activated fatty acids are
      channeled toward one particular metabolic pathway is not well understood on the
      molecular level. We have previously shown that ACSLs localized to either the
      endoplasmic reticulum or to mitochondria can regulate the extent of fatty acid
      uptake. Multiple different long chain ACSLs are expressed simultaneously in the
      same cell type but differ in their subcellular localization. The hypothesis we
      put forward here implies that the spatial organization of ACSL activity is a key
      factor in channeling fatty acids toward a particular metabolic fate.

PMID- 19115051
TI  - A transcriptionally active copia-like retroelement in Citrus limon.
AB  - The plant nuclear genome is largely composed of mobile DNA, which can rearrange
      genomes and other individual gene structure and also affect gene regulation
      through various promoted activities: transposition, insertion, excision,
      chromosome breakage, and ectopic recombination. Ty1-copia-like retrotransposon is
      a widespread class of transposable elements in the plant kingdom, representing a
      large part of the total DNA content. Here, a novel retrotransposon-like sequence
      was isolated and identified as the Ty1-copia-like reverse transcriptase domain
      (named here CLCoy1), based on the homology of known elements. Fluorescence in
      situ hybridization, revealed that CLCoy1 was mainly located in telomeric and sub
      telomeric regions along the Citrus chromosomes. CLCoy1 composes 3.6% of the
      genome and, interestingly, while transposons are mostly specific to a species,
      this element was identified in other Citrus species such as Citrus aurantium,
      Fortunella margarita and Citrus paradisi, but undetected in Poncirus trifoliata.
      We also determined that wounding, salt and cell culture stress produced
      transcriptional activation of this novel retroelement in Citrus limon. The novel
      Ty1-copia-like element CLCoy1 may have played a major role in shaping genome
      structure and size during Citrus species evolution.

PMID- 19115052
TI  - Common variations in 4p locus are related to male completed suicide.
AB  - Suicidal behavior is a multifactorial phenomenon, with a significant genetic
      predisposition. To assess the contribution of genes in the 4p region to suicide
      risk, we genotyped 36 single nucleotide polymorphisms from a 49Mb region on the
      chromosome arm 4p11-16 in a total of 288 male suicide victims and 327 healthy
      male volunteers. The nonsynonymous variants rs1383180 in EVC gene, rs6811863 in
      TBC1D1 gene, rs362272 in HTT gene, and rs734312 in WFS1 gene were associated to
      the male completed suicide. However, only EVC polymorphism remained significant
      after correcting for multiple comparisons (P < .05 after 10 K permutations). The
      function of these genes is not clear yet. WFS1 and HTT are related to the
      unfolded protein response and endoplasmic reticulum stress, and TBC1D1 is a
      GTPase activator. EVC is a protein with transmembrane and leucine zipper domains,
      its function has not been elucidated yet. Further studies are required in order
      to reveal the role of these four polymorphisms in the pathoetiology of suicide.

PMID- 19115053
TI  - Complex quorum-sensing regulatory systems regulate bacterial growth and symbiotic
      nodulation in Mesorhizobium tianshanense.
AB  - LuxR/LuxI-type quorum-sensing systems have been shown to be important for
      symbiotic interactions between a number of rhizobium species and host legumes. In
      this study, we found that different isolates of Mesorhizobium tianshanense, a
      moderately-growing Rhizobium that forms nodules on a number of types of licorice
      plants, produces several different N-acyl homoserine lactone-like molecules. In
      M. tianshanense CCBAU060A, we performed a genetic screen and identified a network
      of regulatory components including a set of LuxI/LuxR-family regulators as well
      as a MarR-family regulator that is required for quorum-sensing regulation.
      Furthermore, compared with the wild-type strains, quorum-sensing deficient
      mutants showed a reduced growth rate and were defective in nodule formation on
      their host plant Glycyrrhiza uralensis. These data suggest that different M.
      tianshanense strains may use diverse quorum-sensing systems to regulate symbiotic
      process.

PMID- 19115054
TI  - Towards biosensors based on conducting polymer nanowires.
AB  - We report the electrochemical deposition of poly(pyrrolepropylic acid) nanowires,
      their covalent modification with antibodies and their conversion into potential
      functional sensor devices. The nanowires and the devices were characterised by
      optical microscopy, fluorescence microscopy, electron microscopy and electrical
      measurements. Fluorescence images, current-voltage (I-V) profiles and real-time
      sensing measurements demonstrated a rapid and highly sensitive and selective
      detection of human serum albumin (HSA), a substance that has been used to
      diagnose incipient renal disease. The detection is based on the selective binding
      of HSA onto anti-HSA that is covalently attached to the nanowires. The binding
      changes the electrical properties of the nanowires thus enabling the real-time
      detection. Whilst the utility of the research was demonstrated for protein
      binding/detection, the technology could easily be designed for the detection of
      other analytes by the modification of polymer nanowires with other analyte
      specific molecules/biomolecules. Therefore, the technology has the potential to
      positively impact broad analytical applications in the biomedical, environmental
      and other sectors.

PMID- 19115055
TI  - Characterization and mRNA expression profile of the TbNre1 gene of the
      ectomycorrhizal fungus Tuber borchii.
AB  - This study focuses on the cloning and characterization of the major nitrogen
      regulator element from the ectomycorrhizal fungus Tuber borchii, TbNre1. Sequence
      analysis of the predicted protein and complementation experiments in Neurospora
      crassa demonstrated that the cloned gene is orthologous to areA/nit-2 gene.
      Transcriptional expression investigations by real-time RT-PCR showed TbNre1 up
      regulation in the presence of nitrate or in the absence of nitrogen during free
      living mycelium growth. On the contrary, TbNre1 mRNA levels remained at basal
      values in the presence of preferred nitrogen sources like ammonium and glutamine.
      Furthermore, TbNre1 mRNA was found to be up-regulated during T. borchii and T.
      platyphyllos interaction. All these data suggest that the regulatory protein
      TBNRE1 could play a major role in regulating N metabolism genes of T. borchii in
      the free living mycelium and in T. borchii-T. platyphyllos interaction. Finally,
      the possible role of the transcription factor TBNRE1 in the induction of
      proteases and virulence-like genes, necessary in ectomycorrhizal establishment,
      was also discussed.

PMID- 19115056
TI  - The clinical and genetical features of 124 children with Familial Mediterranean
      fever: experience of a single tertiary center.
AB  - The aim of the present study was to evaluate the clinical features of childhood
      onset Familial Mediterranean fever (FMF) patients and to assess the phenotype
      genotype correlation. The study included patients with childhood-onset FMF that
      followed up over a period of 18 years in the Division of Pediatric Allergy and
      Immunology clinic. Twelve MEFV mutations were investigated in all patients. The
      patients were classified into four groups according to mutations: 1, M694V
      homozygote; 2, M694V heterozygote; 3, compound heterozygote for M694V; and 4,
      other-other gene mutation group. The following parameters were evaluated: gender,
      age of onset, age at diagnosis, time interval between disease onset and
      diagnosis, fever, abdominal pain, chest pain, arthralgia, arthritis, myalgia,
      vomiting, diarrhea, constipation, headache, erysipela-like erythema, protracted
      febrile myalgia, splenomegaly, hepatomegaly, consanguinity, number of attacks
      before and after treatment, severity score, response to colchicine treatment. Of
      the 124 patients included in the study, 105 had at least one MEFV gene mutation.
      M694V homozygosity was the most common mutation, followed by M694V heterozygotes
      and M694V-M680I compound heterozygotes. Severity score was found significantly
      higher in patients with M694V homozygote and compound heterozygote for M694V
      compared with other groups. The data supported the findings in literature that
      FMF patients with M694V homozygote and compound heterozygote for M694V gene
      mutations experience a more severe clinical course.

PMID- 19115057
TI  - Silicone-induced foreign-body reaction after first metatarsophalangeal joint
      arthroplasty for Jaccoud's arthropathy.
AB  - We report a case of Jaccoud's arthropathy with forefoot plantar callosity. The
      lesser toe metatarsal heads were resected and Swanson's double-stemmed flexible
      hinge implant arthroplasty of the first metatarsophalangeal joint was performed.
      An osteolytic defect had formed around the implant after 2 years. Surgical
      revision comprised implant removal and synovectomy. Histology revealed a foreign
      body reaction with birefringent material in multinucleated giant cells. Because
      the capsuloligamentous system is fragile in Jaccoud's arthropathy, we recommend
      resection arthroplasty or arthrodesis of the first MP joint as an initial
      operative approach.

PMID- 19115058
TI  - Cloak and dagger: the case for adult onset still disease and hemophagocytic
      lymphohistiocytosis.
AB  - Adult onset Still's disease (AOSD) is a rare systemic inflammatory disorder of
      unknown etiology. Systemic onset juvenile idiopathic arthritis (SoJIA) is the
      preferred nomenclature of Still's disease. Strong association with so-called
      macrophage activation syndrome (MAS) may provide a clue to the understanding of
      the distinctive pathogenetic features of SoJIA. MAS is a severe, potentially life
      threatening complication characterized by the excessive activation of well
      differentiated macrophages. It is more appropriately named autoimmune disease
      associated reactive hemophagocytic lymphohistiocytosis (ReHLH), a subset of a
      histiocytic disorder: class II histiocytosis hemophagocytic lymphohistiocytosis
      (HLH). The relation of SoJIA with HLH is still under debate. We propose that MAS,
      HLH, SoJIA, and AOSD are indeed the same disease, in different clinical
      presentations that may be classified based on severity and laboratory findings,
      but with essentially the same physiopathogenesis. We propose that the case
      described by Hong & Lee (Rheumatol Int 2008) was actually an AOSD-associated
      MAS/RHS/ReHLH fulminant disease.

PMID- 19115059
TI  - Efficient, reproducible Agrobacterium-mediated transformation of sorghum using
      heat treatment of immature embryos.
AB  - A number of parameters related to Agrobacterium-mediated infection were tested to
      optimize transformation frequencies of sorghum (Sorghum bicolor L.). A plasmid
      with a selectable marker, phosphomannose isomerase, and an sgfp reporter gene was
      used. First, storing immature spikes at 4 degrees C before use decreased
      frequency of GFP-expressing calli, for example, in sorghum variety P898012 from
      22.5% at 0 day to 6.4% at 5 days. Next, heating immature embryos (IEs) at various
      temperatures for 3 min prior to Agrobacterium infection increased frequencies of
      GFP-expressing calli, of mannose-selected calli and of transformed calli. The
      optimal 43 degrees C heat treatment increased transformation frequencies from
      2.6% with no heat to 7.6%. Using different heating times at 43 degrees C prior to
      infection showed 3 min was optimal. Centrifuging IEs with no heat or heating at
      various temperatures decreased frequencies of all tissue responses; however, both
      heat and centrifugation increased de-differentiation of tissue. If IEs were
      cooled at 25 degrees C versus on ice after heating and prior to infection,
      numbers with GFP-expressing cells increased from 34.2 to 49.1%. The most optimal
      treatment, 43 degrees C for 3 min, cooling at 25 degrees C and no centrifugation,
      yielded 49.1% GFP-expressing calli and 8.3% stable transformation frequency.
      Transformation frequencies greater than 7% were routinely observed using similar
      treatments over 5 months of testing. This reproducible frequency, calculated as
      numbers of independent IEs producing regenerable transgenic tissues, confirmed by
      PCR, western and DNA hybridization analysis, divided by total numbers of IEs
      infected, is several-fold higher than published frequencies.

PMID- 19115060
TI  - Modification and miniaturization of Thermochron iButtons for surgical
      implantation into small animals.
AB  - Thermochron iButtons are being used increasingly by animal physiologists to
      measure long-term patterns of body temperature in reptiles, birds and mammals.
      Typically, iButtons are surgically implanted into the intraperitoneal cavity
      where they measure and store body temperature together with the date and time
      from an onboard real-time clock. In 16-bit resolution, the DS1922L iButton can
      store a total of 4,096 data points over pre-determined sampling intervals.
      iButtons have proved invaluable in measuring patterns of torpor and hibernation
      in animals larger than 70 g. Weighing around 3.5 g after potting with wax,
      iButtons are too heavy and large to implant into animals smaller than 70 g
      because their weight exceeds 5% of the animal's total body weight. This paper
      describes how the stainless steel canister housing the DS 1922L iButton battery
      and circuit board can be removed to reduce the weight of the components to 1.49 g
      after waxing (ready for implantation) without compromising the function or
      battery life of the iButton. The modified iButton can be implanted into animals
      as small as 20-30 g. Calibration data revealed an offset of ca. 1 degrees C on
      average, confirming that iButtons must be calibrated prior to implantation.

PMID- 19115061
TI  - TEP on the tide in killifish (Fundulus heteroclitus): effects of progressively
      changing salinity and prior acclimation to intermediate or cycling salinity.
AB  - Transepithelial potentials (TEP) were measured in killifish, acclimated to
      freshwater (FW), seawater (SW), 33% S: W or cycling salinities relevant to tidal
      cycles in an estuary, and subsequently subjected to salinity changes in
      progressive or random order. Random compared to progressive salinity changes in
      an upward or downward direction in FW- and SW-acclimated fish, respectively, did
      not greatly influence responses to salinity change. Fish acclimated to SW or 33%
      SW as well as those acclimated to cycling salinities behaved similarly (TEP more
      positive than +15 mV in 100% SW, decreasing to approximately 0 mV at 20-40% SW,
      and more negative than -30 mV in FW). In contrast, FW-acclimated fish displayed a
      less pronounced TEP response to salinity (0 mV in FW through 20% SW, increasing
      thereafter to values more positive than +10 mV at 100% SW). We conclude that when
      evaluated under estuarine tidal conditions, the killifish gill exhibits adaptive
      electrical characteristics, opposing Na(+) loss at low salinity and favouring
      Na(+) extrusion at high salinity, changes explained at least in part by the Cl(-)
      to Na(+) permeability ratio. Thus animals living in the estuaries can move to
      lower and higher salinities for short periods with little physiological
      disturbance, but this ability is lost after acclimation to FW.

PMID- 19115062
TI  - Insulin enhances proliferation and viability of human umbilical vein endothelial
      cells.
AB  - This investigation is a follow-up to our previous in vivo studies revealing that
      rapid stretch increases tissue insulin in murine skin flaps, coincident with the
      up-regulation of key angiogenic effectors and enhanced vascularization. In the
      present study, we used human umbilical vein endothelial cells (HUVECs) as an in
      vitro model system to determine the role of insulin in the chemical signals
      regulating the processes of proliferation and viability (survival). MTT-based
      colorimetric methods demonstrated that insulin enhances proliferation and
      survival of HUVECs. Western blot analysis revealed that protein kinase B (pAkt
      [Thr(308)]) and vascular endothelial growth factor (VEGF) were the insulin
      responsive intermediates in proliferating endothelial cells (ECs). In insulin
      enhanced survival, both pAkt (Thr(308)) and pAkt (Ser(473)) were activated in
      HUVECs. However, no change in VEGF expression accompanied pAkt activation. The
      beneficial effects of insulin were abrogated by insulin receptor (IR)/insulin
      like growth factor receptor (IGFR) or phosphoinositide-3 kinase (PI3-K) blockade,
      suggesting that insulin-induced EC proliferation and viability are mediated
      through pIR/pIGFR and PI3-K effectors. These data provide new insights into the
      beneficial effects of insulin on vascularization and tissue viability, providing
      a mechanistic link to the enhancement of healing in acutely stretched skin.

PMID- 19115063
TI  - Galactography acquired with digital mammography in patients with nipple
      discharge: a retrospective analysis.
AB  - PURPOSE: To evaluate the galactographic findings taken with digital mammography
      and to compare the findings between benign and malignant breast diseases.
      MATERIALS AND METHODS: Galactographic findings were retrospectively analyzed and
      compared with histopathological results for 42 patients who showed abnormal
      findings on galactography and had histologically proven diagnoses between January
      2005 and March 2008. A galactography was acquired using full-field digital
      mammography (Hologic Lorad Selenia; Danbury, USA). The difference in
      galactographic findings between malignant and benign breast diseases was analyzed
      using chi(2) test. A value of P < 0.05 was considered statistically significant.
      RESULTS: Of the total 42 cases, 11 cases were malignant breast diseases and 31
      were benign diseases. Common galactographic findings of benign diseases include
      ductal obstruction (48.3%) and single filling defect (51.6%), and common findings
      for malignant tumor include ductal dilatation (72.7%) and stenosis (63.6%).
      Ductal stenosis, microcalcifications or mass adjacent to abnormal duct, multiple
      filling defects, ductal wall irregularity, ductal distortion and irregular
      filling defects were more prevalently seen in malignant cases. A single filling
      defect and lobular filling defect was more prevalently seen in benign cases (P <
      0.05). Ductal dilatation was a common finding in both malignant and benign cases
      with no significant difference. CONCLUSIONS: Ductal lesions were well visualized
      on galactography acquired with a digital mammography. A preoperative diagnostic
      galactography is useful in making a differential diagnosis between benign
      diseases and malignant tumors in patients with pathologic nipple discharge.

PMID- 19115064
TI  - An atypical soybean leucine-rich repeat receptor-like kinase, GmLRK1, may be
      involved in the regulation of cell elongation.
AB  - A leucine-rich repeat receptor-like kinase (LRR-RLK) encoded by one of the genes
      highly expressed in a specific stage of soybean seed development, referred to as
      GmLRK1, was identified and characterized. Examination of its kinase domain
      indicated that GmLRK1 may be a catalytically inactive atypical receptor kinase.
      An autophosphorylation assay confirmed that GmLRK1 is incapable of
      autophosphorylation in vitro. However, the phosphorylation of GmRLK1 could be
      induced after incubation with plant protein extracts, suggesting that some plant
      proteins may interact with GmLRK1 and phosphorylate the protein in vivo. Analyses
      of the expression profiles of GmLRK1 and its Arabidopsis ortholog At2g36570
      revealed that they may be involved in regulation of more fundamental metabolic
      and/or developmental pathways, rather than a specialized developmental program
      such as seed development. Our results further indicate that the GmLRK1 and
      At2g36570 may play a role in the regulation of certain cellular processes that
      lead to cell elongation and expansion.

PMID- 19115065
TI  - Novel biotransformation process of podophyllotoxin to produce podophyllic acid
      and picropodophyllotoxin by Pseudomonas aeruginosa CCTCC AB93066. Part I: process
      development.
AB  - A novel biotransformation process of podophyllotoxin (1) to produce
      picropodophyllotoxin (2) and podophyllic acid (3) was developed in this work.
      Eight bacteria which could modify the structure of podophyllotoxin were screened
      out from the tested fourteen bacteria. The highest conversion of podophyllotoxin
      (i.e., 70.2 +/- 8.0%) was obtained when Pseudomonas aeruginosa CCTCC AB93066 was
      used as biocatalyst, so P. aeruginosa was selected as a typical biocatalyst in
      the following study. Product (2) and (3) were separated through D312 macroporous
      resin and sephadex LH-20 gel column chromatograph. On the basis of (1)H NMR,
      (13)C NMR, ESI-MS and Elemental Analysis, product (2) and (3) were identified as
      picropodophyllotoxin (2) and podophyllic acid (3), respectively. This suggested
      the site-specific isomerization and hydrolization of podophyllotoxin occurred
      during its biotransformation process by P. aeruginosa. For the first time,
      podophyllotoxin was biotransformed into its hydrolytic derivate (i.e.,
      podophyllic acid).

PMID- 19115066
TI  - Model-based process analysis of partial nitrification efficiency under dynamic
      nitrogen loading.
AB  - In this study, the ammonia removal efficiency for high ammonia-containing
      wastewaters was evaluated via partial nitrification. A nitrifier biocommunity was
      first enriched in a fill-and-draw batch reactor with a specific ammonium
      oxidation rate of 0.1 mg NH(4) (-)-N/mg VSS.h. Partial nitrification was
      established in a chemostat at a hydraulic retention time (HRT) of 1.15 days,
      which was equal to the sludge retention time (SRT). The results showed that the
      critical HRT (SRT) was 1.0 day for the system. A maximum specific ammonium
      oxidation rate was achieved as 0.280 mg NH(4) (-)-N/mg VSS.h, which is 2.8-fold
      higher than that obtained in the fill-and-draw reactor, indicating that more
      adaptive and highly active ammonium oxidizers were enriched in the chemostat.
      Dynamic modeling of partial nitrification showed that the maximum growth rate for
      ammonium oxidizers was found to be 1.22 day(-1). Modeling studies also validated
      the recovery period as 10 days.

PMID- 19115067
TI  - Leucine improves the component of isovalerylspiramycins for the production of
      bitespiramycin.
AB  - Bitespiramycin, a group of 4''-O-acylated spiramycins with 4''-O
      isovalerylspiramycins as the major components, is produced by recombinant
      spiramycin-producing strain Streptomyces spiramyceticus harboring a 4''-O
      acyltransferase gene from a carbomycin-producing strain S. mycarofaciens 1748.
      The effects of leucine feeding on the bitespiramycin fermentation, especially the
      synthesis of isovalerylspiramycin components, were investigated. The experiment
      was initially performed in flask culture under the condition of feeding 15.4
      mmol/l of leucine at 72 h fermentation, and the culture without leucine feeding
      was used as control. When 15.4 mmol/l leucine was fed at 72 h, 51.3 +/- 0.33%
      total isovalerylspiramycins was recorded compared to 40.9 +/- 0.26% under the
      control condition after 96 h of fermentation. The improvement of total
      isovalerylspiramycin content was further achieved in 15 l fermentation when 15.4
      mmol/l of leucine was supplemented from 65 to 72 h. These results indicated that
      isovaleryl group derived from leucine catabolism could act as the precursor of
      the 4'' side chain of bitespiramycin, which profoundly enhanced the synthesis of
      isovalerylspiramycins in the bitespiramycin complex.

PMID- 19115068
TI  - Memory for the order of briefly presented numerals in humans as a function of
      practice.
AB  - Inoue and Matsuzawa (Curr Biol 17: R1004-R1005, 2007) showed that with an
      accuracy of approximately 79%, the juvenile chimpanzee, Ayumu, could recall the
      position and order of a random subset of five Arabic numerals between one and
      nine when those numerals were presented for only 210 ms on a computer touch
      screen before being masked with white squares. None of nine humans working on the
      same task approached this level of accuracy. Inoue and Matsuzawa (2007) claimed
      this performance difference was evidence of a memorial capacity in young
      chimpanzees that was superior to that seen in adult humans. While the between
      species performance difference they report is apparent in their data, so too is a
      large difference in practice on their task: Ayumu had many sessions of practice
      on their task before terminal performances were measured; their human subjects
      had none. The present report shows that when two humans are given practice in the
      Inoue and Matsuzawa (2007) memory task, their accuracy levels match those of
      Ayumu.

PMID- 19115069
TI  - Cell adhesion mechanisms and stress relaxation in the mechanics of tumours.
AB  - Tumour cells usually live in an environment formed by other host cells, extra
      cellular matrix and extra-cellular liquid. Cells duplicate, reorganise and deform
      while binding each other due to adhesion molecules exerting forces of measurable
      strength. In this paper, a macroscopic mechanical model of solid tumour is
      investigated which takes such adhesion mechanisms into account. The extracellular
      matrix is treated as an elastic compressible material, while, in order to define
      the relationship between stress and strain for the cellular constituents, the
      deformation gradient is decomposed in a multiplicative way distinguishing the
      contribution due to growth, to cell rearrangement and to elastic deformation. On
      the basis of experimental results at a cellular level, it is proposed that at a
      macroscopic level there exists a yield condition separating the elastic and
      dissipative regimes. Previously proposed models are obtained as limit cases, e.g.
      fluid-like models are obtained in the limit of fast cell reorganisation and
      negligible yield stress. A numerical test case shows that the model is able to
      account for several complex interactions: how tumour growth can be influenced by
      stress, how and where it can generate cell reorganisation to release the stress
      level, how it can lead to capsule formation and compression of the surrounding
      tissue.

PMID- 19115070
TI  - First magnetic resonance imaging-guided aortic stenting and cava filter placement
      using a polyetheretherketone-based magnetic resonance imaging-compatible
      guidewire in swine: proof of concept.
AB  - The purpose of this study was to demonstrate feasibility of percutaneous
      transluminal aortic stenting and cava filter placement under magnetic resonance
      imaging (MRI) guidance exclusively using a polyetheretherketone (PEEK)-based MRI
      compatible guidewire. Percutaneous transluminal aortic stenting and cava filter
      placement were performed in 3 domestic swine. Procedures were performed under MRI
      guidance in an open-bore 1.5-T scanner. The applied 0.035-inch guidewire has a
      PEEK core reinforced by fibres, floppy tip, hydrophilic coating, and paramagnetic
      markings for passive visualization. Through an 11F sheath, the guidewire was
      advanced into the abdominal (swine 1) or thoracic aorta (swine 2), and the stents
      were deployed. The guidewire was advanced into the inferior vena cava (swine 3),
      and the cava filter was deployed. Postmortem autopsy was performed. Procedural
      success, guidewire visibility, pushability, and stent support were qualitatively
      assessed by consensus. Procedure times were documented. Guidewire guidance into
      the abdominal and thoracic aortas and the inferior vena cava was successful.
      Stent deployments were successful in the abdominal (swine 1) and thoracic (swine
      2) segments of the descending aorta. Cava filter positioning and deployment was
      successful. Autopsy documented good stent and filter positioning. Guidewire
      visibility through applied markers was rated acceptable for aortic stenting and
      good for venous filter placement. Steerability, pushability, and device support
      were good. The PEEK-based guidewire allows either percutaneous MRI-guided aortic
      stenting in the thoracic and abdominal segments of the descending aorta and
      filter placement in the inferior vena cava with acceptable to good device
      visibility and offers good steerability, pushability, and device support.

PMID- 19115071
TI  - AngioJet thrombectomy for occluded dialysis fistulae: outcome data.
AB  - This study evaluates AngioJet thrombectomy of occluded autogenous dialysis
      fistulae and polytetrafluoroethylene (PTFE) grafts in a UK hemodialysis
      population. Comparison is made with published data of alternative percutaneous
      thrombectomy methods. All patients with occluded dialysis fistulae who sought
      care at the Royal Liverpool University Hospital between October 2006 and June
      2008 were included in the study. All patients were treated with the AngioJet
      Rheolytic Thrombectomy Device (Possis, Minneapolis, MN). Demographics, time of
      occlusion, adjunctive therapies, complications, and follow-up data have been
      prospectively recorded. A total of 64 thrombectomy procedures were performed in
      48 patients. Forty-four autogenous fistulas were treated in 34 patients (19
      brachiocephalic, 8 radiocephalic, and 7 transposed brachiobasilic). Twenty PTFE
      grafts were treated in 14 patients (9 brachioaxillary, 3 brachiocephalic loop
      grafts, 1 brachiobasilic, and 1 femoro-femoral). The average length of occlusion
      was 24 cm. Average time to intervention was 4 days. Immediate primary patency was
      91%. Primary patency at 1, 3, and 6 months, respectively, was 71%, 60%, and 37%.
      Secondary patency at 3, 6, and 12 months was 87%, 77%, and 62%, respectively.
      Angioplasty was carried out in all procedures. Patients required stent insertion
      in 34 of the 64 thrombectomies to treat angioplasty-resistant stenoses.
      Complications included a puncture-site hematoma, and three angioplasty-related
      vein ruptures in one patient, all treated with covered stent grafts. Two cases of
      distal brachial arterial embolization were successfully treated by
      thrombosuction. AngioJet thrombectomy in dialysis access occlusion is safe and
      effective, comparing favorably with other methods.

PMID- 19115072
TI  - Dysphagia in a patient with bilateral medial medullary infarcts.
AB  - Bilateral medial medullary infarct is a rare stroke syndrome and only a handful
      of cases have been described. Dysphagia as a manifestation of medullary infarcts
      is well recognized but often associated with lateral medullary infarct. Bilateral
      medial medullary infarcts are commonly associated with severe dysphagia in
      addition to a number of other signs and symptoms. We describe a patient who had
      bilateral medial medullary infarct with severe dysphagia in addition to
      quadriplegia and respiratory difficulty, and analyze infarct topography with
      respect to dysphagia, risk factors, vascular territories involved, and prognosis
      in view of previously reported cases.

PMID- 19115073
TI  - Local connectivity of neutral networks.
AB  - This paper studies local connectivity of neutral networks of RNA secondary and
      pseudoknot structures. A neutral network denotes the set of RNA sequences that
      fold into a particular structure. It is called locally connected, if in the limit
      of long sequences, the distance of any two of its sequences scales with their
      distance in the n-cube. One main result of this paper is that lambda(n) = n(
      1/2+Delta) is the threshold probability for local connectivity for neutral
      networks, considered as random subgraphs of n-cubes. Furthermore, we analyze
      local connectivity for finite sequence length and different alphabets. We show
      that it is closely related to the existence of specific paths within the neutral
      network. We put our theoretical results into context with folding algorithms into
      minimum-free energy RNA secondary and pseudoknot structures. Finally, we relate
      our structural findings with dynamics by discussing the role of local
      connectivity in the context of neutral evolution.

PMID- 19115074
TI  - Metabolic factors and subsequent risk of hepatocellular carcinoma by hepatitis
      virus infection status: a large-scale population-based cohort study of Japanese
      men and women (JPHC Study Cohort II).
AB  - OBJECTIVE: The association between metabolic factors and hepatocellular carcinoma
      (HCC) has not been well clarified. We prospectively examined whether metabolic
      factors predicts the subsequent risk of HCC in the Japan Public Health Center
      based Prospective Study Cohort II, in consideration of hepatitis virus infection
      status. METHODS: A total of 17,590 subjects aged 40-69 participating in a
      questionnaire and health checkup survey during 1993-1994 were followed for
      incidence of HCC through 2006. A total of 102 cases of HCC were newly documented.
      Hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated for
      metabolic factors controlling for potential confounding factors. RESULTS: The
      presence of metabolic factors in the aggregate was associated with a
      significantly increased risk of HCC, especially with hepatitis virus infection.
      HCC was positively associated particularly with high glucose (HR = 1.75, CI =
      1.11-2.74) and overweight (HR = 2.22, CI = 1.42-3.48). Results were similar when
      analyses were limited to subjects with HCV infection. CONCLUSIONS: Although
      metabolic factors in the aggregate may be associated with an increased risk of
      HCC, the main contributors to this association under HCV infection appear to be
      overweight and high glucose. Improvement of these factors may be a crucial target
      in preventing progression to HCC in those with HCV infection.

PMID- 19115075
TI  - Ginkgo biloba (EGB 761) affects apoptosis and nitric-oxide synthases in
      testicular torsion: an experimental study.
AB  - INTRODUCTION: We investigated the effect of ginkgo biloba on germ cell apoptosis
      and also on expressions of endothelial (eNOS) and inducible (iNOS) nitric oxide
      synthases after testicular torsion. MATERIALS AND METHODS: Thirty-two Wistar
      albino rats were randomly assigned into four groups. Torsion/detorsion (T/D) was
      performed on the rats in group 1, group 2 received ginkgo biloba for a month
      before T/D, group 3 received only gingko biloba for a month, and group 4 was the
      sham group. Left testicular torsion was created in group 1 and group 2, and the
      testes were untwisted and replaced in the scrotum for reperfusion. No procedure
      was applied to group 3, and after 1 month, testes were removed in all groups.
      RESULTS: Mean apoptotic cell, eNOS, and iNOS were increased in group 1. Group 2
      showed significantly decreased apoptotic cells, eNOS, and iNOS in testes compared
      to group 1 (P < 0.05). The rats in group 3 had significantly decreased apoptotic
      cell, eNOS, and iNOS values, like the sham group (P < 0.05), and this group
      provided basal values. CONCLUSIONS: Ginkgo biloba, as a free radical scavenger,
      seems to have a protective role against apoptosis in testicular ischemia
      reperfusion injury.

PMID- 19115076
TI  - Beneficial effects of magnesium in chronic renal failure: a foe no longer.
AB  - Magnesium plays a critical role in cellular physiology in humans, regulating many
      fundamental functions. In the general population its deficiency is associated
      with many disorders, the most significant being cardiovascular diseases. The role
      of magnesium in many aspects of end-stage renal disease (ESRD) may be also very
      important, although this has not been explored in depth. The most significant of
      these roles are use of magnesium salts as phosphate binders and its ability to
      inhibit the development or progression of vascular calcification. Moreover, serum
      magnesium suppresses parathyroid hormone excretion, whereas high magnesium
      dialysate may result in intradialytic hemodynamic stability. Data provided by
      recent studies on these issues have promoted promising renewed interest in the
      role of magnesium in ESRD and its possible favorable therapeutic application in
      these patients. Further large studies are needed to establish its efficacy and
      safety, and, probably, to re-evaluate its appropriate concentration in
      hemodialysis and continuous ambulatory peritoneal dialysis (CAPD) fluids.

PMID- 19115077
TI  - Creatinine reabsorption by the aged kidney.
AB  - AIM: The handling of renal creatinine in human beings has classically been
      described as the result of two particular physiological processes: glomerular
      filtration and proximal tubular secretion. However, there are particular
      physiological situations in which tubular creatinine reabsorption has been
      documented, such as in the case of healthy newborns and premature babies. We
      performed a prospective study in order to evaluate if there is tubular creatinine
      reabsorption in healthy elderly people. PATIENTS AND METHOD: We studied
      prospectively nine healthy volunteers, four of them young (20-33 years old) and
      the remaining five, old (65-73 years old). Since creatinine is secreted in the
      proximal tubules, and its secretion can be completely blocked by cimetidine
      administration, a creatinine clearance with cimetidine reliably represents the
      glomerular filtration rate. Therefore, if the ratio creatinine clearance
      (Ccr)/creatinine clearance with cimetidine (CcrWC) is higher than one, this would
      indicate net creatinine secretion, whereas a ratio lower than one would indicate
      a net renal creatinine tubular reabsorption; a ratio equal to one indicates
      creatinine filtration. Finally, the Ccr, CcrWC, and Ccr/CcrWC ratios were
      compared between the young and old group. STATISTICAL TESTS: Mann-Whitney and
      Wilcoxon tests were used. RESULTS: As expected, creatinine clearance in the
      elderly was significantly lower than in the young [Ccr: 74.4 ml/min (47.9-100.9)
      (old) vs. 153.8 ml/min (108.3-199.2) (young), p = 0.014]. Similarly, the
      creatinine clearance with cimetidine (CcrWC) was significantly lower in the
      elderly compared to the young [CcrWC: 81.8 ml/min (69.2-94.5) (old) vs. 122.5
      ml/min (82.6-162.4) (young), p = 0.028]. The ratio of Ccr/CcrWC was 0.9 in the
      elderly vs. 1.26 in the young (p = 0.014), indicating net creatinine reabsorption
      in the elderly and net creatinine secretion in the young. CONCLUSION: Our
      findings indicate that there seems to be a net reabsorption of creatinine in the
      renal tubules of healthy old persons.

PMID- 19115078
TI  - Relationship between carotid artery intima-media thickness and brachial artery
      flow-mediated dilation in peritoneal dialysis patients.
AB  - BACKGROUND AND AIM: Carotid artery intima-media thickness (CIMT) and brachial
      artery flow-mediated dilation percentage (FMD%) are two commonly used parameters
      for detecting subclinical atherosclerosis. However, studies investigating the
      relationship between CIMT and brachial artery FMD% in different populations have
      produced conflicting results. The aim of this study was to determine the
      relationship between CIMT and brachial artery FMD% in patients on peritoneal
      dialysis (PD) METHODS: Fifty-two PD patients without known cardiovascular disease
      and 30 age-gender matched controls were included in the study. Endothelial
      function was determined using ultrasonography (US) to measure the FMD of the
      brachial artery, and this parameter was expressed as the percentage change from
      the baseline diameter of the brachial artery (FMD%). We also measured CIMT by US
      and analysed the relationship between CIMT and brachial FMD%. RESULTS: The CIMT
      was significantly higher in patients than in the control group (0.84 +/- 0.08 vs.
      0.75 +/- 0.06 mm, P < 0.01), whereas brachial artery FMD% was lower in patients
      than in the controls (8.2 +/- 5.0 vs. 11.7 +/- 5.5%, P < 0.01). There was no
      significant correlation between CIMT and FMD% (r = -0.004, P = 0.94). CONCLUSION:
      Although PD patients are known to be characterized by an impaired flow-mediated
      vasodilatation of brachial artery and increased in CIMT, we did not find a
      significant correlation between FMD% and CIMT in our PD patient cohort. One
      possible explanation for our results is that each method measures a different
      aspect and stage of atherosclerosis.

PMID- 19115079
TI  - Penis covering and simultaneous urethral replacement by scrotal skin for severe
      penile and urethral necrosis.
AB  - OBJECTIVES: Penile strangulation with severe necrosis and concomitant significant
      tissue loss is a challenging problem for reconstructive surgery. Final
      reconstruction and tissue augmentation of the resected penis often require multi
      step plastic reconstruction. METHODS: Severe damage of the phallus with gangrene
      and septic complication caused by a bronze ring were first conservatively treated
      to achieve dry gangrene. The glans of the penis, the whole penile skin, and
      distal third of the corpus spongiosum with the urethra were lost to necrosis,
      resulting in a missing urethral segment on the penis. Surgery was performed 3
      months after removing the metal ring; a one-step skin and urethral reconstruction
      was done. RESULTS: Good functional and esthetic results could be achieved by mid
      term follow-up. CONCLUSION: In long-lasting penile strangulation with damaged
      blood supply, further surgery and treatment are needed in addition to immediate
      decompression. Most commonly in these situations, amputation seems to be the best
      and easiest action to be taken. However, our case shows that even in a most
      severe situation, careful conservative treatment allows preserving the phallus,
      and subsequently reconstruction enables reaching the best functional and esthetic
      results.

PMID- 19115080
TI  - Cell senescence: the future of ageing?

PMID- 19115081
TI  - The in vitro kinetics of senescence of Fischer 344 rat embryo fibroblasts.
AB  - The kinetics of replicative senescence have been determined in three independent
      cultures of fibroblasts derived from Fischer rat embryos (FREF). In each case the
      growth fraction was measured by immunocytochemical staining for proliferating
      cell nuclear antigen (PCNA) and by metabolic labeling using bromodeoxyuridine
      (BrdU). FREF cultures entered senescence at an average of 20.4 population
      doublings. The growth fraction declined smoothly as measured by both kinetic
      techniques. The average rate of decline of the growth fraction observed using
      BrdU was -0.79 +/- 0.12% population doubling(-1) which was closely comparable to
      the loss of PCNA reactivity (-0.80 +/- 0.11% population doubling(-1)). We
      conclude that senescence in FREF cultures occurs as the result of a progressive
      loss of the culture growth fraction rather than a sudden abrupt collapse.

PMID- 19115083
TI  - Three new species of Anthocephalum Linton, 1890 (Cestoda: Tetraphyllidea) from
      dasyatid stingrays of the Gulf of California.
AB  - Three new species of Anthocephalum Linton, 1890 are described from dasyatid
      stingrays collected in the Gulf of California. Anthocephalum michaeli n. sp. is
      described from Dasyatis longus (Garman). This species most closely resembles A.
      alicae Ruhnke, 1994, but differs from this species in proglottid number. A. lukei
      n. sp. is also described from D. longus. This new species is most similar to A.
      cairae Ruhnke, 1994, but differs from that species in marginal loculi number and
      number of proglottids. The third new species, A. currani n. sp., is described
      from D. brevis (Garman). This species is most similar to A. centrurum (Southwell,
      1925) Ruhnke, 1994, but differs from that species in marginal loculi number,
      number of testes and ovarian length. Phyllobothrium kingae Schmidt, 1978 is also
      consistent in morphology with species of Anthocephalum and is transferred to this
      genus, forming the new combination Anthocephalum kingae n. comb. This species
      most closely resembles A. michaeli n. sp., but differs in testicular shape. This
      brings the total number of species of Anthocephalum to nine. The transfer of the
      species Phyllobothrium arctowskii Wojciechowska, 1991, P. georgiense
      Wojciechowska, 1991, P. rakusai Wojciechowska, 1991 and P. siedleckii
      Wojciechowska, 1991 to Anthocephalum is not warranted, as these four species lack
      a posteriorly recurved cirrus-sac and a sinuous vagina, and have vitelline
      follicles uninterrupted by the ovary. Of the nine known species, all are
      parasitic in batoid fishes, and six are found in species of Dasyatis Garman. The
      phylogenetic status of Anthocephalum species in relationship to Rhinebothroides
      Mayes, Brooks & Thorson, 1981, Pararhineothroides Zamparo, Brooks & Barriga, 1999
      and other rhinebothriin taxa is discussed.

PMID- 19115084
TI  - Gnathia trimaculata n. sp. (Crustacea: Isopoda: Gnathiidae), an ectoparasite
      found parasitising requiem sharks from off Lizard Island, Great Barrier Reef,
      Australia.
AB  - Gnathia trimaculata n. sp. is described from one black tip reef shark Carcharinus
      melanopterus Quoy & Gaimard and four grey reef sharks C. amblyrhynchos Bleeker
      collected off Lizard Island, Great Barrier Reef, Australia. Third-stage juveniles
      (praniza 3) were maintained in fresh seawater until they moulted into adults.
      Male adults emerged seven days post-removal (d.p.r) of pranizae from host fishes,
      whereas the female pranizae completed their moult into adult females 24 d.p.r.
      Distinctive features include the relatively large size of all stages and the
      unique mediofrontal process of the male, which is divided into two lobes forming
      a key-hole shape between them. The female frontal border is characterised by
      paired simple, pappose setae on the sides of the mid-dorsal area, as well as four
      long, pappose setae on the mid-dorsal region. The pranizae have eight teeth on
      each mandible. Live pranizae have stripes and three pairs of distinctive black
      spots within yellow circles on the sides of the pereonites and this pigmentation
      pattern persists in the adults. This represents the second description of a
      gnathiid parasitising elasmobranchs off Australia.

PMID- 19115085
TI  - Monogeneans of the grouper Epinephelus tauvina (Perciformes, Serranidae) off
      Moorea, French Polynesia, with a description of Pseudorhabdosynochus pai n. sp.
      (Monogenea: Diplectanidae).
AB  - Specimens of the greasy grouper Epinephelus tauvina (Forsskal), caught off
      Moorea, French Polynesia, harboured four species of gill monogeneans. The
      diplectanid Pseudorhabdosynochus pai n. sp. is characterised by an extremely big
      male quadriloculate organ (inner length 77 mum, cone length 15, tube length 47),
      the largest of all members of the genus, and a sclerotised vagina with a very
      complex structure, including three secondary chambers instead of one as in most
      species. Pseudorhabdosynochus sp. is a species of the 'cupatus group'; this
      species is not formally described but various measurements are provided. The
      ancyrocephalid Haliotrema sp. and the capsalid Benedenia sp. were rare; they are
      both mentioned but not described. The diplectanid fauna of E. tauvina corresponds
      to the pattern already found in a clade of grouper species, the members of which
      often harbour both a species of the 'cupatus group' and another species of
      Pseudorhabdosynochus Yamaguti, 1958.

PMID- 19115086
TI  - Steinernema boemarei n. sp. (Nematoda: Steinernematidae), a new entomopathogenic
      nematode from southern France.
AB  - A new entomopathogenic nematode, Steinernema boemarei n. sp., is described from
      southern France. Morphological, molecular (28S and ITS rDNA sequence data) and
      cross-hybridisation studies were used for diagnostics and identification
      purposes. Both molecular and morphological data indicate that the new species
      belongs to the 'glaseri-group' of Steinernema spp. Key morphological diagnostic
      traits for S. boemarei n. sp. include the presence of prominent deirids (cervical
      papillae) on adult males, the morphology of the spicules and gubernaculum, and
      the arrangement of the 23 genital papillae of the first generation males.
      Additionally, morphometric traits of the third-stage infective juvenile,
      including total body length (mean 1,103 micron), tail length (mean 86 micron),
      location of the excretory pore (mean 91 micron), and D% (mean 63), E% (mean 106)
      and H% (mean 41) values are definitive. In addition to these morphological
      characters, analysis of both 28S and ITS rDNA sequences depict this Steinernema
      species as a distinct and unique entity.

PMID- 19115087
TI  - Diagnoses of and illustrated key to the species of Ixodes Latreille, 1795 (Acari:
      Ixodidae) from Brazil.
AB  - The current Brazilian Ixodes fauna is composed of the following eight species: I.
      amarali Fonseca, 1935; I. aragaoi Fonseca, 1935; I. auritulus Neumann, 1904; I.
      fuscipes Koch, 1844; I. loricatus Neumann, 1899; I. luciae Senevet, 1940; I.
      paranaensis Barros-Battesti, Arzua, Pichorim & Keirans, 2003; and I. schulzei
      Aragao & Fonseca, 1951. Further studies are needed to establish the taxonomic
      status of I. serrafreirei Amorim, Gazeta, Bossi & Linhares, 2003, a recently
      proposed species based solely on the nymphal stage. We present an up-to-date key
      to adults of the currently valid Brazilian species of Ixodes based on scanning
      electron microscopy. The relationships between Brazilian and other Neotropical
      Ixodes are also discussed.

PMID- 19115088
TI  - Comparison of indirect fluorescent antibody test (IFAT) and slide enzyme linked
      immunosorbent assay (SELISA) for diagnosis of Babesia bigemina infection in
      bovines.
AB  - An indirect fluorescent antibody test (IFAT) and slide enzyme linked
      immunosorbent assay (SELISA) were standardized for the detection of antibodies
      specific to Babesia bigemina in experimentally infected bovine calves and
      subsequently used for the screening of naturally infected bovine and bubaline
      sera. In experimentally infected calves positive reactivity was detected in sera
      at the earliest on day 7 by both the tests. Serological studies for detection of
      B. bigemina specific antibodies in 180 cow and 120 buffalo serum samples procured
      from endemic zones of Uttar Pradesh and Punjab revealed 56.11% and 23.33%
      seropositivity, respectively, both by SELISA and IFAT. Variation in the
      reactivity pattern between these tests was found to be non significant. The
      sensitivity of SELISA was determined to be 94.85% whereas the specificity was
      90.85% in comparison to IFAT. The agreement between the two tests by kappa
      statistics at 95% confidence interval revealed kappa- value of 0.853 that depicts
      almost a perfect degree of agreement. The findings employing experimental as well
      as test sera from cattle and buffalo from some of the tick infested zones of
      India suggested that SELISA could be a useful tool for seroprevalence studies on
      babesiosis, as the test is less cost intensive with high levels of sensitivity
      and specificity.

PMID- 19115089
TI  - Analysis of early survival of Holstein-Friesian heifers of diverse sire origins
      on commercial dairy farms in Kenya.
AB  - The use of imported semen within the Holstein-Friesian cattle population in Kenya
      has contributed to increased milk production per cow, however, information on how
      this has impacted on functional traits, particularly early life survival and
      reproductive performance is scarce. This study evaluated age at first calving
      (AFC), survival to age at first calving, and survival to four years of age using
      survival analyses techniques, in Holstein-Friesian cattle on four dairy farms in
      Kenya. The heritability estimate obtained for AFC was 0.15 +/- 0.06 for an
      average AFC of 1058 days. Animals sired by New Zealand and Australian born bulls
      had the earliest average AFC (907 days). On average, 25% of all the heifers born
      were culled prior to attaining a first calving, while 34% were culled prior to
      four years of age. Though the highest proportion of losses was due to unspecified
      reasons, the relative risk of being culled was highest when an animal had a
      specific disease, and the first 60 days of life were the most critical for
      survival. Daughters of sires from South-Africa and Israel tended to have better
      survival rates than those sired by bulls originating from other regions.
      Unfavourable selection towards animals sired by Kenyan born bulls was evident.
      The economic implications of the high rate of early mortality need to be
      evaluated in order to assist livestock producers make informed decisions on
      choice of sires for breeding.

PMID- 19115090
TI  - Fluoridated hydroxyapatite/titanium dioxide nanocomposite coating fabricated by a
      modified electrochemical deposition.
AB  - Fluoridated hydroxyapatite/titanium dioxide nanocomposite coating was
      successfully fabricated by a modified electrochemical deposition technique. F(-)
      ions, nanoscaled TiO(2) particles and 6% H(2)O(2) was added into the electrolyte,
      and ultrasonication was also performed to prepare this nanocomposite coating. The
      microstructure, phase composition, dissolution rate, bonding strength and in
      vitro cellular responses of the composite coating were investigated. The results
      show that the composite coating was uniform and dense owing to the effects of
      H(2)O(2) and ultrasonication. The thickness of the composite coating was ~5 mum
      and scanning electron microscopy revealed that nanoscaled TiO(2) particles were
      imbedded uniformly between FHA crystals. The addition of F(-) and TiO(2) reduced
      the crystallite size and increased the crystallinity of HA in FHA/TiO(2)
      composite coating. In addition, the composite coating shows higher bonding
      strength and lower dissolution rate than pure HA coating, and the in vitro
      bioactivity of FHA/TiO(2) composite coating was not affected as compared with
      pure HA coating.

PMID- 19115091
TI  - Development of a novel porous cryo-foam for potential wound healing applications.
AB  - This body of work describes the development of a porous hydrogel for wound
      healing applications. In the present study poly (vinyl alcohol) (PVA) and poly
      (acrylic acid) (PAA) based hydrogels were prepared, and their properties were
      examined. Varying concentrations of the polymers and distilled water were used to
      prepare the hydrogels. The use of a high shear mixer, for foaming the PVA and
      PVA/PAA gels, and how this physical change can affect the structure and porosity
      of the hydrogel in question, represents a key feature of this work. The
      mechanical and thermal properties were determined by parallel plate rheometry and
      modulated differential scanning calorimetry (MDSC) respectively. The results
      indicated that the hydrogels containing low concentration of PVA and high volume
      of H(2)O are significantly weaker than those synthesised with higher
      concentrations of PVA. The thermal analysis shows distinct endotherms and
      provides evidence of crystallisation. The chemical structure of the hydrogels was
      confirmed by means of attenuated total reflectance Fourier transform infrared
      spectroscopy (ATR-FTIR).

PMID- 19115092
TI  - Proliferation and function of MC3T3-E1 cells on freeze-cast hydroxyapatite
      scaffolds with oriented pore architectures.
AB  - Previous work by the authors showed that hydroxyapatite (HA) scaffolds with
      different types of oriented microstructures and a unique 'elastic-plastic'
      mechanical response could be prepared by unidirectional freezing of suspensions.
      The objective of the present work was to evaluate the in vitro cellular response
      to these freeze-cast HA scaffolds. Unidirectional scaffolds with approximately
      the same porosity (65-70%) but different pore architectures, described as
      'lamellar' (pore width = 25 +/- 5 microm) and 'cellular' (pore diameter = 100 +/-
      10 microm), were evaluated. Whereas both groups of scaffolds showed excellent
      ability to support the proliferation of MC3T3-E1 pre-osteoblastic cells on their
      surfaces, scaffolds with the cellular-type microstructure showed far better
      ability to support cell proliferation into the pores and cell function. These
      results indicate that freeze-cast HA scaffolds with the cellular-type
      microstructure have better potential for bone repair applications.

PMID- 19115093
TI  - Preparation and characterization of nano-hydroxyapatite/polyamide 66 composite
      GBR membrane with asymmetric porous structure.
AB  - In this study, a nano-hydroxyapatite/polyamide 66 (nHA/PA66) composite with good
      biocompatibility and high bioactivity is employed to develop novel asymmetric
      structure porous membranes for guided bone regeneration (GBR). FT-IR and XRD
      analyses suggest that chemical bonds are formed between nHA and PA66 both in
      composite powders and membranes. The fabricated membranes show gradient porous
      structure. SEM analysis reveal that pores less than 10 microm and pores with a
      size ranging from 30 microm to 200 microm distribute in the micropore layer and
      the spongy structure layer, respectively. The surface energy determination also
      reveals that the fabricated membranes have asymmetric surface properties on the
      two sides of the membrane. The incorporation of nHA in PA66 matrix improves the
      properties of the membrane. The elongation at break and the tensile strength of
      nHA/PA66-40 suggest that the composite membrane has good strength and toughness.
      The rough porous structure surface with high surface energy of nHA/PA66 composite
      membrane may be beneficial to promote cells immobility and differentiation into a
      mature phenotype producing mineralized matrix. The biocompatibility, bioactivity,
      osteoconductivity, asymmetric porous structure, mechanical properties and
      hydrophilicity of the composite membrane can meet the requirement of GBR
      technique.

PMID- 19115094
TI  - Proceedings of the 5th Congress of the Latin-American Society for Artificial
      Organs and Biomaterials. June 22-25, 2008. Ouro Preto, Brazil.

PMID- 19115095
TI  - Evaluation of a multi-layer microbraided polylactic acid fiber-reinforced conduit
      for peripheral nerve regeneration.
AB  - We evaluated peripheral nerve regeneration using a biodegradable multi-layer
      microbraided polylactic acid (PLA) fiber-reinforced conduit. Biodegradability of
      the PLA conduit and its effectiveness as a guidance channel were examined as it
      was used to repair a 10 mm gap in the rat sciatic nerve. As a result, tube
      fragmentation was not obvious and successful regeneration through the gap
      occurred in all the conduits at 8 weeks after operation. These results indicate
      the superiority of the PLA materials and suggest that the multi-layer
      microbraided PLA fiber-reinforced conduits provide a promising tool for neuro
      regeneration.

PMID- 19115096
TI  - Hybrid scoring and classification approaches to predict human pregnane X receptor
      activators.
AB  - PURPOSE: The human pregnane X receptor (PXR) is a transcriptional regulator of
      many genes involved in xenobiotic metabolism and excretion. Reliable prediction
      of high affinity binders with this receptor would be valuable for pharmaceutical
      drug discovery to predict potential toxicological responses MATERIALS AND
      METHODS: Computational models were developed and validated for a dataset
      consisting of human PXR (PXR) activators and non-activators. We used support
      vector machine (SVM) algorithms with molecular descriptors derived from two
      sources, Shape Signatures and the Molecular Operating Environment (MOE)
      application software. We also employed the molecular docking program GOLD in
      which the GoldScore method was supplemented with other scoring functions to
      improve docking results. RESULTS: The overall test set prediction accuracy for
      PXR activators with SVM was 72% to 81%. This indicates that molecular shape
      descriptors are useful in classification of compounds binding to this receptor.
      The best docking prediction accuracy (61%) was obtained using 1D Shape Signature
      descriptors as a weighting factor to the GoldScore. By pooling the available
      human PXR data sets we revealed those molecular features that are associated with
      human PXR activators. CONCLUSIONS: These combined computational approaches using
      molecular shape information may assist scientists to more confidently identify
      PXR activators.

PMID- 19115098
TI  - Expressed emotion, human agency, and schizophrenia: toward a new model for the EE
      relapse association.
AB  - Although there is a clear statistical association between expressed emotion (EE)
      and schizophrenic relapse, our understanding of the mechanisms underlying this
      relationship is underdeveloped. This study tested a theoretical model in which
      caregivers' perceptions of their ill relative's agency underlie the EE-relapse
      association. To evaluate this model, we completed qualitative and quantitative
      analyses of narratives provided by individuals caring for a relative with
      schizophrenia. The results indicate that high-EE caregivers perceive the
      expression of symptoms as stemming from their ill relative's agency more
      frequently than low-EE caregivers. This was true for both high-EE-criticism and
      high-EE-emotional overinvolvement caregivers. High-EE and low-EE caregivers did
      not differ in their perceptions of the role of their ill relative's agency with
      regard to the control of symptoms. The findings suggest that EE may be a proxy
      risk factor for caregivers' perceptions of their ill relative's agency.

PMID- 19115099
TI  - Sexual harassment and posttraumatic stress disorder: damages beyond prior abuse.
AB  - This study examined the extent to which harassment experiences correlate with
      posttraumatic stress disorder (PTSD) symptoms, and whether diagnosable PTSD on
      the basis of sexual harassment occurs after accounting for prior PTSD, prior
      sexual abuse, and prior psychological dysfunction. The sample consisted of a two
      wave panel of 445 women who had received a domestic violence protective order
      from a Kentucky court. Hierarchical linear and logistic analyses confirmed that
      sexual harassment experiences were significantly correlated with PTSD symptoms
      after controlling for an extensive set of trauma variables measured in both the
      baseline and follow up interviews. Our findings lend further evidence that claims
      of PTSD from sexual harassment may be credible even if claimants have been
      victims of other forms of trauma.

PMID- 19115100
TI  - Maturity in adolescent and young adult offenders: the role of cognitive control.
AB  - This study examined the role of cognitive control in explaining the psychosocial
      maturity of adolescent (n = 43) and young adult male (n = 40) offenders. We
      separated psychosocial maturity into prosocial and criminal components, which
      were statistically unrelated and were explained by different variables.
      Individuals with higher levels of prosocial maturity were older, had better
      proactive cognitive control, and had better short-term memory than those with
      lower levels of prosocial maturity. Individuals with higher levels of criminal
      maturity were older and had better reactive cognitive control than those with
      lower levels of criminal maturity. We discuss the implications of these findings
      with regard to juvenile justice policy and practice.

PMID- 19115101
TI  - Commercial sexual practices before and after legalization in Australia.
AB  - The nature of sex work changes over time for many reasons. In recent decades
      around the world, there has been movement toward legalization and control of sex
      economies. Studies of the possible impact of legalization mainly have focused on
      sexually transmitted infections and violence, with little attention to change in
      the diversity of sexual services provided. This study examined the practices of
      sex workers before and after legalization of prostitution. Cross-sectional
      surveys of comparable samples of female sex workers were conducted in 1991 (N =
      200, aged 16-46 years) and 2003 (N = 247, aged 18-57 years) in Queensland,
      Australia, spanning a period of major change in regulation of the local industry.
      In 2003, male clients at brothels and private sole operators (N = 161; aged 19-72
      years) were also interviewed. Over time, there was a clear increase in the
      provision of "exotic" sexual services, including bondage and discipline,
      submission, fantasy, use of sex toys, golden showers, fisting, and lesbian double
      acts, while "traditional" services mostly remained at similar levels (with
      substantial decrease in oral sex without a condom). Based on comparisons of self
      reports of clients and workers, the demand for anal intercourse, anal play, and
      urination during sex apparently exceeded supply, especially in licensed brothels.
      Within this population, legalization of sex work coincided with a substantial
      increase in diversity of services, but it appears that in the regulated working
      environments, clients who prefer high risk practices might not dictate what is
      available to them.

PMID- 19115102
TI  - The relationships between states' DUI penalties and HIV-positive adults' drinking
      behaviors.
AB  - Evidence that persons with HIV who reside in states with stricter DUI penalties
      drink less might suggest that changes to alcohol policy might improve the health
      of persons with HIV and reduce the rate of new infections. Using multi-level
      modeling and data from the national HIV Cost and Services Utilization Study, we
      examined how states' DUI-related fines, jail time, license suspension, and court
      referred treatment/education policies were related to past month drinking/not (n
      = 2,255) and among drinkers (n = 1,117), drinking frequency, drinks per occasion,
      and engagement in frequent heavy drinking. Fine strictness was negatively related
      to all outcomes. Residents in states with court-referred treatment/education had
      more current drinkers. Results suggested that punitive DUI policies might curb a
      variety of drinking behaviors whereas harm reduction DUI policies (e.g., court
      treatment programs) might have been established in response to higher drinking
      rates.

PMID- 19115103
TI  - Introduction to the special section on practice contexts: a glimpse into the
      nether world of public mental health services for children and families.

PMID- 19115104
TI  - Molecular characterization of circulating tumor cells in large quantities of
      contaminating leukocytes by a multiplex real-time PCR.
AB  - Detection of circulating tumor cells (CTCs) in whole blood from metastatic cancer
      patients by the CellSearch CTC Test (Veridex LLC, Warren, NJ, USA) has been shown
      to have clinical relevance. In addition to enumeration, there is great interest
      in molecular characterization of these CTCs. We aimed to establish a robust
      method to perform mRNA expression analysis of multiple genes by a real-time
      reverse transcriptase (RT)-PCR on small numbers of CTCs enriched from whole blood
      by the CellSearch system. Despite the 4 log depletion of leukocytes after
      CellSearch enrichment, the CTC-enriched fractions still contained leukocytes, in
      particular B-lymphocytes, which severely interfered with our CTC-specific gene
      expression profiling. After extensive washing and leukocyte-specific depletion by
      anti-CD45 coated magnetic beads prior to CellSearch enrichment, the number of
      leukocytes present in the enriched fraction was still high (range 60-929).
      However, by using a set of genes with no or minor expression by leukocytes, we
      succeeded to perform quantitative gene expression profiling specific for as
      little as one breast cancer CTC present in a CTC-enriched environment typically
      containing over 800 contaminating leukocytes. Our method allows molecular
      characterization specific for as little as one CTC, and can be used to expand the
      understanding of the biology of metastasis and, potentially, to improve patient
      management.

PMID- 19115105
TI  - HER2 as marker for the detection of circulating tumor cells.

PMID- 19115106
TI  - Elevated plasma endoglin (CD105) predicts decreased response and survival in a
      metastatic breast cancer trial of hormone therapy.
AB  - Background Endoglin (CD105) is a co-receptor for TGF-beta, is expressed by human
      vascular endothelial cells, and plays a major role in angiogenesis. Materials and
      methods Pretreatment EDTA plasma from 224 metastatic breast cancer patients
      enrolled in a phase III 2nd-line hormone therapy trial and 50 control subjects
      were assayed for endoglin using an ELISA. Results The female control group (n =
      50) plasma endoglin upper limit of normal was defined as the mean + 2 SD (8.7
      ng/ml). The breast cancer patient plasma endoglin was 6.40 +/- 2.23 ng/ml (range
      3.00-19.79 ng/ml). Elevated plasma endoglin levels were detected in 26 of 224
      patients (11.6%). Patients with elevated plasma endoglin had a reduced clinical
      benefit rate (CR + PR + Stable) (15 vs. 42%) (P = 0.01) to hormone therapy. TTP
      was shorter for patients with elevated plasma endoglin, but did not reach
      statistical significance (P = 0.2). Patients with elevated plasma endoglin had
      decreased overall survival (median 645 vs. 947 days) (P = 0.005). Conclusion
      Elevated pretreatment plasma endoglin levels predicted for decreased clinical
      benefit and a shorter overall survival in metastatic breast cancer patients
      treated with 2nd-line hormone therapy.

PMID- 19115108
TI  - Passing through the wall: on outings, exodus, angels, and the ark.
AB  - Classicists have argued that angels in Christian theology were modeled on the
      eunuchs of antiquity; with angels providing the same services to the Lord in
      Heaven that eunuchs provided to emperors on Earth. I apply this idea toward
      understanding the cherubim on the ark in Exodus 25 and the death of Aaron's sons
      in Leviticus 10. I also suggest that the angel-eunuch analogy can help us
      understand the psychological impact of androgen deprivation therapy on modern
      prostate cancer patients. Appreciating this analogy can help prostate cancer
      patients accept and adapt to the changes they experience.

PMID- 19115107
TI  - Age-dependent increase in desmosterol restores DRM formation and membrane-related
      functions in cholesterol-free DHCR24-/- mice.
AB  - Cholesterol is a prominent modulator of the integrity and functional activity of
      physiological membranes and the most abundant sterol in the mammalian brain.
      DHCR24-knock-out mice lack cholesterol and accumulate desmosterol with age. Here
      we demonstrate that brain cholesterol deficiency in 3-week-old DHCR24(-/-) mice
      was associated with altered membrane composition including disrupted detergent
      resistant membrane domain (DRM) structure. Furthermore, membrane-related
      functions differed extensively in the brains of these mice, resulting in lower
      plasmin activity, decreased beta-secretase activity and diminished Abeta
      generation. Age-dependent accumulation and integration of desmosterol in brain
      membranes of 16-week-old DHCR24(-/-) mice led to the formation of desmosterol
      containing DRMs and rescued the observed membrane-related functional deficits.
      Our data provide evidence that an alternate sterol, desmosterol, can facilitate
      processes that are normally cholesterol-dependent including formation of DRMs
      from mouse brain extracts, membrane receptor ligand binding and activation, and
      regulation of membrane protein proteolytic activity. These data indicate that
      desmosterol can replace cholesterol in membrane-related functions in the DHCR24(
      /-) mouse.

PMID- 19115109
TI  - Betulinic acid induces cytochrome c release and apoptosis in a Bax/Bak
      independent, permeability transition pore dependent fashion.
AB  - Betulinic acid (BetA) is a plant-derived pentacyclic triterpenoid that exerts
      potent anti-cancer effects in vitro and in vivo, but is non toxic to
      untransformed cells. In our previous study we observed that BetA consistently
      induced cell death in a broad panel of tumor cell lines. Apoptosis induced by
      BetA involves activation of caspases, PARP cleavage and DNA fragmentation and was
      suggested to depend on the mitochondrial pathway. However, conflicting results
      have been reported with respect to the role of the pro- and anti-apoptotic
      members of the Bcl-2 family, which are often aberrantly regulated in tumors and
      thereby confer growth and survival advantages. Here we show that BetA-induced
      apoptosis critically depends on the release of cytochrome c from the mitochondria
      and formation of the apoptosome. Nevertheless, over-expression of Bcl-2 or Bcl-XL
      only provides limited protection against BetA-induced apoptosis. More
      importantly, Bax/Bak deficient cells are as sensitive to BetA as their wild-type
      counterparts, suggesting that cytochrome c is released in a non-classical
      fashion. In agreement, pre-incubation with cyclosporin A indicated a crucial role
      for the mitochondrial permeability transition pore (PT) in the induction of
      apoptosis. Our observations therefore indicate that BetA affects mitochondria and
      induces cytochrome c release directly via PT Pore. This is only temporarily
      prevented by anti-apoptotic members of the Bcl-2 family, but independent of Bax
      and Bak. These findings help to explain the remarkable broad efficacy of BetA
      against tumor cells of different origin and its effect in tumor cells that are
      resistant to other chemotherapeutic agents.

PMID- 19115110
TI  - Co-solvent evaporation method for enhancement of solubility and dissolution rate
      of poorly aqueous soluble drug simvastatin: in vitro-in vivo evaluation.
AB  - A number of synthesized chemical molecules suffer from low aqueous solubility
      problems. Enhancement of aqueous solubility, dissolution rate, and
      bioavailability of drug is a very challenging task in drug development. In the
      present study, solubility and dissolution of poorly aqueous soluble drug
      simvastatin (SIM) was enhanced using hydrophilic, low viscosity grade polymer
      hydroxypropyl methylcellulose (HPMC K(3)LV). The co-solvent evaporation method
      was developed for efficient encapsulation of hydrophobic drug in polymer micelles
      of HPMC K(3)LV. Spray drying and rotaevaporation method were applied for solvent
      evaporation. Co-solvent-evaporated mixture in solid state was determined by
      differential scanning calorimetry (DSC), X-ray diffraction studies (XRD),
      scanning electron microscopy, and Fourier-transform infrared spectroscopy. In
      vitro-in vivo studies were performed on co-solvent-evaporated mixture and
      compared with SIM. In vivo study was conducted on healthy albino rats (Wister
      strain), and formulations were administered by oral route. Results of the study
      show the conversion of crystalline form of SIM into amorphous form. The
      dissolution rate was remarkably increased in co-solvent-evaporated mixtures
      compared to SIM. co-solvent-evaporated mixtures showed better reduction in total
      cholesterol and triglyceride levels than the SIM. The low-viscosity grade HPMC
      acts as a surfactant, which enhances the wetting of drug and thus improves the
      solubility of drug. The co-solvent evaporation method provides good encapsulation
      efficiency and produces amorphous form of SIM, which gave better solubility and
      dissolution than the crystalline SIM.

PMID- 19115111
TI  - Design and evaluation of a novel matrix type multiple units as biphasic
      gastroretentive drug delivery systems.
AB  - A biphasic gastroretentive floating drug delivery system with multiple-unit mini
      tablets based on gas formation technique was developed to maintain constant
      plasma level of a drug concentration within the therapeutic window. The system
      consists of loading dose as uncoated core units, and prolonged-release core units
      are prepared by direct compression process; the latter were coated with three
      successive layers, one of which is seal coat, an effervescent (sodium
      bicarbonate) layer, and an outer polymeric layer of polymethacrylates. The
      formulations were evaluated for quality control tests, and all the parameters
      evaluated were within the acceptable limits. The system using Eudragit RL30D and
      combination of them as polymeric layer could float within acceptable time. The
      drug release was linear with the square root of time. The rapid floating and the
      controlled release properties were achieved in this present study. When compared
      with the theoretical release profile, the similarity factor of formulation with
      coating of RS:RL (1:3)-7.5%, was observed to be 74, which is well fitted into
      zero-order kinetics confirming that the release from formulation is close to
      desired release profile. The stability samples showed no significant change in
      dissolution profiles (p > 0.05). In vivo gastric residence time was examined by
      radiograms, and it was observed that the units remained in the stomach for about
      5 h.

PMID- 19115112
TI  - Solubility enhancement of lovastatin by modified locust bean gum using solid
      dispersion techniques.
AB  - The aim of the present study was to improve the solubility of poorly water
      soluble drug lovastatin (LS) by solid dispersion (SD) techniques using modified
      locust bean gum (MLBG) as a carrier. The locust bean gum (LBG) was modified by
      heating and there observed irreversible decrease in viscosity, whereas swelling
      property remains unaffected. The advantage of modification of LBG was illustrated
      by difference in dissolution profiles of their SD. Effect of polymer
      concentration and methods of preparation on solubility enhancement were studied
      using solubility and dissolution studies, respectively. The result of solubility
      study showed increase in solubility of LS with increase in concentration of MLBG.
      It was found that the dissolution rate of LS from its SD was dependent on the
      method of preparation of solid dispersions. Dissolution study revealed that the
      modified solvent evaporation is most convenient and effective method for
      solubility enhancement of poorly water soluble drug LS, among various methods of
      preparation of SD. The prepared SDs were characterized by differential scanning
      calorimetry, scanning electron microscopy, and X-ray diffraction study. In vivo
      study was performed by measuring 3-hydroxy-3-methyl-glutaryl-coenzyme A (HMG Co
      A) reductase inhibition activity. Significant reduction in HMG Co-A reductase
      activity was observed in case of solid dispersions of LS than plain LS. In
      conclusion, MLBG could be used as a potential carrier in enhancing the
      dissolution rate and bioavailability of LS.

PMID- 19115113
TI  - Bibliography - RW MOWRY.

PMID- 19115114
TI  - Cost-effective method for growing three-dimensional cell cultures in
      extracellular matrix extract.
AB  - Three-dimensional (3-D) cell cultures are advantageous for modeling complex
      cellular behavior. A major issue with 3-D cultures grown in Engelbreth-Holm-Swarm
      (EHS) extracellular matrix extract, however, is the expense. We describe here a
      simple method using a rubber gasket laid over a coverslip, which provides
      sufficient 3-D area filled with a minimal amount of EHS, resulting in cost
      effective 3-D cellular cultures that are easy to manipulate.

PMID- 19115115
TI  - Robert W. Mowry, M.D. Some thoughts about his contributions to the Biological
      Stain Commission.

PMID- 19115116
TI  - Tribute to Bob Mowry.

PMID- 19115117
TI  - Influence of protoporphyrin IX amino acid substituents on affinity to human
      breast adenocarcinoma MCF-7 cells.
AB  - The ability of protoporphyrin IX (PP IX) to enter neoplastic cells is used for
      diagnosis and photodynamic therapy. We present here the effects of PP IX and
      three amino acid derivatives on MCF-7 cell viability. The fluorescence of each
      substance was examined using confocal microscopy. Our results show that
      diarginine diprotoporphyrinate (PP(Arg)2) has satisfactory fluorescence to
      evaluate the rate of accumulation within cells. We have determined the times at
      which the accumulation begins and reaches a plateau, as well as cellular
      localization of PP(Arg)2 in MCF-7 cells.

PMID- 19115119
TI  - Oxidative-induced membrane damage in diabetes lymphocytes: effects on
      intracellular Ca(2 +) homeostasis.
AB  - Oxidative stress is linked to several human diseases, including diabetes.
      However, the intracellular signal transduction pathways regulated by reactive
      oxygen species (ROS) remain to be established. Deleterious effects of ROS stem
      from interactions with various ion transport proteins such as ion channels and
      pumps, primarily altering Ca(2 +) homeostasis and inducing cell dysfunction. This
      study characterized the Ca(2 +) transport system in lymphocytes of patients with
      type-2 diabetes, evaluating the possible correlation between cell modifications
      and the existence of specific oxidative stress damage. Lymphocytes from type-2
      diabetes patients displayed oxidative stress features (accumulation of some ROS
      species, membrane peroxidation, increase in protein carbonyls, increase in SOD
      and Catalase activity) and Ca(2 +) dyshomeostasis (modified voltage-dependent and
      inositol 1,4,5-triphosphate-mediated Ca(2 +) channel activities, decrease in Ca(2
      +) pumps activity). The data support a correlation between oxidative damage and
      alterations in intracellular Ca(2 +) homeostasis, possibly due to modification of
      the ionic control in lymphocytes of type-2 diabetes patients.

PMID- 19115120
TI  - Inhibition of reactive oxygen species and pre-neoplastic lesions by quercetin
      through an antioxidant defense mechanism.
AB  - There is a correlation between oxidative stress generated by diethylnitrosamine
      (DEN) metabolism and liver cancer development. Quercetin is a flavonoid with anti
      carcinogenic and antioxidant properties. This study demonstrates the mechanism of
      action for the chemopreventive effect of quercetin. A 10 mg/kg dose of quercetin
      produced drastic effect, when it is administrated 2 h before DEN; at 24 days post
      DEN, a 70.3% and 66.2% decrease in total area and number of preneoplastic lesions
      were observed, respectively. At 12 h post-DEN, quercetin inhibited levels of
      lipid peroxidation by 40%. Quercetin increased the levels of both GSH and of
      total glutathione, it increased the GSH/GSSG index and it caused a rapid and
      simultaneous elevation in the activities of superoxide dismutase, glutathione
      peroxidase and catalase. In conclusion, the quercetin mechanism of action is due
      to promote the enzymatic and non-enzymatic antioxidant defense system during the
      initiation of hepatocarcinogenesis.

PMID- 19115121
TI  - Application of multivariate statistical techniques for differentiation of ripe
      banana flour based on the composition of elements.
AB  - Major (sodium, potassium, calcium, magnesium) and minor elements (iron, copper,
      zinc, manganese) and one heavy metal (lead) of Cavendish banana flour and Dream
      banana flour were determined, and data were analyzed using multivariate
      statistical techniques of factor analysis and discriminant analysis. Factor
      analysis yielded four factors explaining more than 81% of the total variance: the
      first factor explained 28.73%, comprising magnesium, sodium, and iron; the second
      factor explained 21.47%, comprising only manganese and copper; the third factor
      explained 15.66%, comprising zinc and lead; while the fourth factor explained
      15.50%, comprising potassium. Discriminant analysis showed that magnesium and
      sodium exhibited a strong contribution in discriminating the two types of banana
      flour, affording 100% correct assignation. This study presents the usefulness of
      multivariate statistical techniques for analysis and interpretation of complex
      mineral content data from banana flour of different varieties.

PMID- 19115122
TI  - Vitamin A status does not contribute to the residual goiter in schoolchildren of
      Isfahan, an iodine replenished area.
AB  - Two thousand three hundred and thirty-one schoolchildren were selected by multi
      stage random sampling. The thyroid size was estimated by inspection and
      palpation. The urinary iodine concentration and serum retinol (SR) were measured
      in 454 and 468 schoolchildren, respectively. Overall, 32.9% of 2,331 children had
      goiter. The median urinary iodine concentration was 195.5 microg/l. The mean+/
      standard deviation of SR in goitrous and non-goitrous children was 34.84+/-7.28
      microg/dl and 33.73+/-7.87 microg/dl, respectively (P=0.14). There was no child
      with vitamin A deficiency (SR <20 microg/dl) in both the goitrous and non
      goitrous groups. The prevalence of subjects with low vitamin A status (SR <30
      microg/dl) in the goitrous and non-goitrous groups was 27.7% and 33.3%,
      respectively (P=0.21). In conclusion, the present study reveals that vitamin A
      deficiency and low vitamin A status are not among the contributing factors of
      goiter persistence in the studied area, and the role of other responsible factors
      should be investigated.

PMID- 19115123
TI  - Antioxidant capacity and phenolic acids of virgin coconut oil.
AB  - The antioxidant properties of virgin coconut oil produced through chilling and
      fermentation were investigated and compared with refined, bleached and deodorized
      coconut oil. Virgin coconut oil showed better antioxidant capacity than refined,
      bleached and deodorized coconut oil. The virgin coconut oil produced through the
      fermentation method had the strongest scavenging effect on 1,1-diphenyl-2
      picrylhydrazyl and the highest antioxidant activity based on the beta-carotene
      linoleate bleaching method. However, virgin coconut oil obtained through the
      chilling method had the highest reducing power. The major phenolic acids detected
      were ferulic acid and p-coumaric acid. Very high correlations were found between
      the total phenolic content and scavenging activity (r=0.91), and between the
      total phenolic content and reducing power (r=0.96). There was also a high
      correlation between total phenolic acids and beta-carotene bleaching activity.
      The study indicated that the contribution of antioxidant capacity in virgin
      coconut oil could be due to phenolic compounds.

PMID- 19115124
TI  - The recovery rate at the human terminal ileum of an orally administered non
      digestive oligosaccharide (raffinose).
AB  - We clarified how raffinose, one of the non-digestive oligosaccharides, reaches
      the large intestine. Seven healthy male volunteers were given a test meal
      containing 10.0 g raffinose. A double-lumen tube was placed in the terminal
      ileum, and the ileal contents were aspirated through the tube. The amounts of
      raffinose were orally administered and collected from the terminal ileum and were
      compared with each other. The result was that the mean+/-standard error
      percentage of the amount of ingested raffinose collected in the terminal ileum
      was 97.1+/-2.4%. Furthermore, the average times taken for 20%, 40%, 60% and 80%
      of raffinose to reach the terminal ileum were 2.0+/-0.6 h, 2.6+/-0.7 h, 3.6+/-0.7
      h and 4.9+/-0.7 h, respectively. In conclusion, approximately 100% of ingested
      raffinose was recovered in the terminal ileum in the present study. This
      corresponds with the present generally accepted definition of a dietary fibre.

PMID- 19115125
TI  - Proteomic analyses of monocyte-derived macrophages infected with human
      immunodeficiency virus type 1 primary isolates from Hispanic women with and
      without cognitive impairment.
AB  - The signature for human immunodeficiency virus type 1 (HIV-1) neurovirulence
      remains a subject of intense debate. Macrophage viral tropism is one prerequisite
      but others, including virus-induced alterations in innate and adaptive immunity,
      remain under investigation. HIV-1-infected mononuclear phagocytes (MPs;
      perivascular macrophages and microglia) secrete toxins that affect neurons. The
      authors hypothesize that neurovirulent HIV-1 variants affect the MP proteome by
      inducing a signature of neurotoxic proteins and thus affect cognitive function.
      To test this hypothesis, HIV-1 isolates obtained from peripheral blood of women
      with normal cognition (NC) were compared to isolates obtained from women with
      cognitive impairment (CI) and to the laboratory adapted SF162, a spinal fluid R5
      isolate from a patient with HIV-1-associated dementia. HIV-1 isolates were used
      to infect monocyte-derived macrophages (MDMs) and infection monitored by secreted
      HIV-1 p24 by enzyme-linked immunosorbent assay (ELISA). Cell lysates of
      uninfected and HIV-1-infected MDMs at 14 days post infection were fractionated by
      cationic exchange chromatography and analyzed by surface enhanced laser
      desorption ionization time of flight (SELDI-TOF) using generalized estimating
      equations statistics. Proteins were separated by one-dimensional sodium dodecyl
      sulfate-polyacrylamide gel electrophoresis (1D SDS-PAGE) and identified by tandem
      mass spectrometry. Levels of viral replication were similar amongst the HIV-1
      isolates, although higher levels were obtained from one viral strain obtained
      from a patient with CI. Significant differences were found in protein profiles
      between virus-infected MDMs with NC, CI, and SF162 isolates (adjusted P value
      after multiple testing corrections, or q value <.10). The authors identified 6
      unique proteins in NC, 7 in SF162, and 20 in CI. Three proteins were common to
      SF162 and CI strains. The MDM proteins linked to infection with CI strains were
      related to apoptosis, chemotaxis, inflammation, and redox metabolism. These
      findings support the hypothesis that the macrophage proteome differ when infected
      with viral isolates of women with and without CI.

PMID- 19115126
TI  - Increased frequency of alpha-synuclein in the substantia nigra in human
      immunodeficiency virus infection.
AB  - The frequency of neurodegenerative markers among long surviving human
      immunodeficiency virus (HIV)-infected individuals is unknown, therefore, the
      present study investigated the frequency of alpha-synuclein, beta-amyloid, and
      HIV-associated brain pathology in the brains of older HIV-infected individuals.
      We examined the substantia nigra of 73 clinically well-characterized HIV-infected
      individuals aged 50 to 76 years from the National NeuroAIDS Tissue Consortium. We
      also examined the frontal and temporal cortical regions of a subset of 36
      individuals. Neuritic alpha-synuclein expression was found in 16% (12/73) of the
      substantia nigra of the HIV+cases and none of the older control cases (0/18).
      beta-Amyloid deposits were prevalent and found in nearly all of the HIV+cases
      (35/36). Despite these increases of degenerative pathology, HIV-associated brain
      pathology was present in only 10% of cases. Among older HIV+adults, HIV
      associated brain pathology does not appear elevated; however, the frequency of
      both alpha-synuclein and beta-amyloid is higher than that found in older healthy
      persons. The increased prevalence of alpha-synuclein and beta-amyloid in the
      brains of older HIV-infected individuals may predict an increased risk of
      developing neurodegenerative disease.

PMID- 19115128
TI  - The cellular transcription factor, CCAAT enhancer-binding protein alpha (C/EBP
      alpha), has the potential to activate the bovine herpesvirus 1 immediate-early
      transcription unit 1 promoter.
AB  - Following acute infection, bovine herpesvirus-1 (BHV-1) establishes a lifelong
      latent infection in sensory neurons of trigeminal ganglia. BHV-1 periodically
      reactivates from latency and is shed as infectious virus. The latency-related
      (LR) gene is abundantly expressed in trigeminal ganglia of infected calves, and
      proteins encoded by the LR gene are necessary for reactivation from latency. We
      previously demonstrated that a novel LR protein interacts with a host
      transcription factor, CCAAT enhancer-binding protein alpha (C/EBPalpha).
      C/EBPalpha increases plaque-forming efficiency when cotransfected with BHV-1 DNA
      and its expression is induced in neurons during reactivation from latency (Meyer
      et al, 2007, J Virol 81: 59-67). The ability of C/EBPalpha to bind DNA is
      necessary for stimulating productive infection, suggesting C/EBPalpha stimulates
      viral transcription. We tested whether C/EBPalpha could trans-activate the BHV-1
      immediate early transcription unit 1 (IEtu1) promoter because the IEtu1 promoter
      activates expression of two viral genes (bICP0 and bICP4) that stimulate
      producitve infection. In the current study, We demonstrate that C/EBPalpha and
      the BHV-1 trans-inducing factor (bTIF) synergistically trans-activate IEtu1
      promoter activity. However, bICP0 and C/EBPalpha did not synergistically trans
      activate IEtu1 promoter activity. Deletion of IEtu1 promoter sequences
      demonstrated that C/EBPalpha by itself could trans-activate a truncated IEtu1
      promoter, suggesting sequences in the distal region of the IEtu1 promoter
      negatively regulate C/EBPalpha activtiy. These studies suggest that C/EBPalpha
      stimulates productive infection and reactivation from latency, in part, by
      cooperating with bTIF to activate IEtu1 promoter activity.

PMID- 19115127
TI  - Bovine herpesvirus type 1 (BoHV-1) anterograde neuronal transport from trigeminal
      ganglia to nose and eye requires glycoprotein E.
AB  - The requirement of bovine herpesvirus type 1 (BoHV-1) envelope protein gE (Us8
      homolog) for establishment of latency and reactivation in trigeminal ganglia (TG)
      was examined. Although BHV-1 gE-rescued and gE-deleted viruses were isolated from
      nasal or ocular swabs during primary infection, only the gE-rescued virus was
      isolated following dexamethasone-induced reactivation. Furthermore, gC protein
      expression, which requires viral DNA replication for its expression, was detected
      in TG of calves infected with either virus following reactivation. These studies
      suggest that gE is required for anterograde transport of BoHV-1 from neuronal
      cell bodies in the TG to their nerve processes.

PMID- 19115129
TI  - Bovine herpesvirus 5 induces an overproduction of nitric oxide in the brain of
      rabbits that correlates with virus dissemination and precedes the development of
      neurological signs.
AB  - We herein report an investigation of nitric oxide (NO) levels, a candidate
      molecule for neuronal toxicity and dysfunction, in the brain of rabbits during
      experimental neurological infection by bovine herpesvirus 5 (BoHV-5).
      Spectrophotometry for NO products (NO(2) and NO(3)) revealed that NO levels were
      significantly increased (F(4, 40) = 3.33; P <.02) in several regions of the brain
      of rabbits with neurological disease, correlating with moderate to high BoHV-5
      titers. Immunohistochemistry of brain regions revealed a group of cells with
      neuronal and astrocyte morphology expressing the enzyme inducible NO synthase
      (iNOS) close to virus antigen-positive neurons. In addition, the investigation of
      nitric oxide levels between 2 and 6 days post infection (d.p.i.) revealed an
      initial increase in NO levels in the olfactory bulb and cortex (OB/OC) and
      anterior cortex (AC) at day 3 p.i., correlating with the initial detection of
      virus. As the infection proceeded, increased NO levels-and infectivity-were
      progressively being detected in the OB/CO and AC at day 4 p.i. (F(12, 128) =
      2.82; P <.003); at day 5 p.i. in several brain regions (P <.003 in the OB/OC);
      and at day 6 p.i. in all regions (P <.003) but the thalamus. These results show
      that BoHV-5 replication in the brain of rabbits induces an overproduction of NO.
      The increase in NO levels in early infection correlated spatially and temporally
      with virus dissemination within the brain and preceded the development of
      neurological signs. Thus, the overproduction of NO in the brain of BoHV-5
      infected rabbits may be a component of the pathogenesis of BoHV-5-induced
      neurological disease.

PMID- 19115131
TI  - Theiler's murine encephalomyelitis virus attachment to the gastrointestinal tract
      is associated with sialic acid binding.
AB  - DA and GDVII are strains of Theiler's murine encephalomyelitis virus (TMEV). DA
      virus mutant DApB encodes VP2 puff B of GDVII, whereas DApBL2M contains VP1 loop
      II of GDVII with a point mutation in VP2 puff B. Neuraminidase treatment of cells
      inhibited infection by DA and DApB, but not GDVII or DApBL2M viruses; sialic acid
      (SA) binding correlated with virus persistence. In virus binding assays to
      intestine sections, all four TMEVs bound goblet cells and the mucus of the
      epithelium that was SA dependent. Therefore, differences in SA composition on
      different cell types can affect tropism and infection.

PMID- 19115130
TI  - Contrasting roles for Valpha14+ natural killer T cells in a viral model for
      multiple sclerosis.
AB  - Most natural killer (NK) T cells express an invariant Valpha14 T-cell receptor.
      To explore the contribution of NKT cells in an animal model for multiple
      sclerosis, Theiler's murine encephalomyelitis virus (TMEV) infection, TMEV
      infected mice were treated with Valpha14 antibody. Treatment during the early
      stage of infection delayed the onset of demyelinating disease with higher
      interleukin-4 production, whereas administration during the late stage or weekly
      resulted in more severe demyelination with enhanced virus persistence. The effect
      of in vivo depletion of NKT cells differed depending on the stage of infection,
      suggesting contrasting roles for NKT cells over the disease course.

PMID- 19115132
TI  - Expression of the urokinase plasminogen activator receptor (uPAR) and its ligand
      (uPA) in brain tissues of human immunodeficiency virus patients with
      opportunistic cerebral diseases.
AB  - The urokinase plasminogen activator receptor (uPAR) and its ligand (uPA) play an
      important role in cell migration and extracellular proteolysis. We previously
      described uPAR/uPA overexpression in the cerebrospinal fluid (CSF) and brain
      tissues of patients with human immunodeficiency virus (HIV)-related cerebral
      diseases. In this study, we examined uPAR/uPA expression by immunohistochemistry
      (IHC) in brains of HIV patients with opportunistic cerebral lesions and in HIV
      positive/negative controls. uPAR was found in macrophages/microglia with the
      highest levels in cytomegalovirus (CMV) encephalitis, toxoplasmosis, and
      lymphomas; in cryptococcosis and progressive multifocal leukoencephalopathy (PML)
      cases, only a few positive cells were found and no positivity was observed in
      controls. uPA expression was demonstrated only in a few macrophages/microglia and
      lymphocytes in all the cases and HIV-positive controls without different pattern
      of distribution; no uPA immunostaining was found in cryptococcosis and HIV
      negative controls. The higher expression of uPAR/uPA in most of the opportunistic
      cerebral lesions supports their role in these diseases, suggesting their
      contribution to tissue injury.

PMID- 19115134
TI  - Neurons and oligodendrocytes in the mouse brain differ in their ability to
      replicate Semliki Forest virus.
AB  - Semliki Forest virus (SFV) provides an experimental model of acute virus
      encephalitis and virus-induced demyelinating disease. Two marker viruses
      expressing fluorescent proteins as part of the replicase or the structural open
      reading frame were used to evaluate virus replication in cells of the adult mouse
      brain. Both marker viruses established a high-titer infection in the adult mouse
      brain. As determined by location, morphology, and immunostaining with neural cell
      type-specific phenotypic markers, both viruses infected neurons and
      oligodendrocytes but not astrocytes. Determination of eGFP expression from either
      the replicase or the structural open-reading frame coupled with immunostaining
      for either the virus structural protein or the virus nonstructural protein-3
      readily distinguished cells at early and late stages of infection. Neurons but
      not oligodendrocytes rapidly down-regulated virus replication. Rapid down
      regulation of virus replication was also observed in mature but not immature
      primary cultures of rat hippocampal neurons. This study demonstrates for the
      first time that in vivo central nervous system (CNS) cells differ in their
      ability to suppress alphavirus replication.

PMID- 19115135
TI  - Arthroderma vanbreuseghemii infection in three family members with kerion and
      tinea corporis.
AB  - We present a familial infection caused by Arthroderma vanbreuseghemii. The
      proband is a 4-year-old boy, who had played with rabbits at his rabbit-farm
      neighbor. He complained of pruritus and pain in his scalp, which displayed
      redness, alopecia and painful cysts and eventually discharged pus and scabbed.
      Several erythema on his face and abdomen were also presented. He was diagnosed as
      having impetigo but antibacterial agents were not effective and his clinical
      condition did not improve. Several days later, his parents also developed facial
      erythema and scaling. The development of a kerion in the boy and tinea corporis
      in his parents were diagnosed based on the positive KOH examination. Morphologic
      and biochemical characteristics confirmed that their infections were caused by
      the zoophilic Trichophyton mentagrophytes, while sequencing of the internal
      transcribed spacer (ITS) 1/4 polymerase chain reaction products, amplified from
      primary culture isolates, established its Arthroderma vanbreuseghemii lineage.
      Random amplified polymorphic DNA (RAPD) analysis indicated these isolates might
      be the same strain and that infection cruciata occurred in this family. Semi
      quantitative analysis of these strains indicated multiple and main enzymatic
      activities of alkaline phosphatase, beta-glucosaccharase. The boy was cured
      through treatment with itraconazole 100 mg/day orally in combination with topical
      washes with 2% ketoconazole shampoo, and his parents were successfully treated by
      topical application of terbinafine cream.

PMID- 19115133
TI  - Dual lentivirus infection potentiates neuroinflammation and neurodegeneration:
      viral copassage enhances neurovirulence.
AB  - Infection by multiple lentiviral strains is recognized as a major driving force
      in the human immunodeficiency virus/acquired immunodeficiency syndrome (HIV/AIDS)
      epidemic, but the neuropathogenic consequences of multivirus infections remain
      uncertain. Herein, we investigated the neurovirulence and underlying mechanisms
      of dual lentivirus infections with distinct viral strains. Experimental feline
      immunodeficiency virus (FIV) infections were performed using cultured cells and
      an in vivo model of AIDS neuropathogenesis. Dual infections were comprised of two
      FIV strains (FIV-Ch and FIV-PPR) as copassaged or superinfected viruses, with
      subsequent outcome analyses of host immune responses, viral load,
      neuropathological features, and neurobehavioral performance. Dual infections of
      feline macrophages resulted in greater IL-1beta (interleukin-1beta), TNF-alpha
      (tumor necrosis factor alpha), and IDO (indoleamine 2,3-dioxygenase) expression
      and associated neurotoxic properties. FIV coinfection and sequential
      superinfection in vivo also induced greater IL-1beta, TNF-alpha, and IDO
      expression in the basal ganglia (BG) and cortex (CTX), compared to the monovirus-
      and mock-infected groups, although viral loads were similar in single virus- and
      dual virus-infected animals. Immunoblot analyses disclosed lower synaptophysin
      immunoreactivity in the CTX resulting from FIV super- and coinfections.
      Cholinergic and GABAergic neuronal injury was evident in the CTX of animals with
      dual FIV infections. With increased glial activation and neuronal loss in dual
      FIV-infected brains, immunohistochemical analysis also revealed elevated
      detection of cleaved caspase-3 in dysmorphic neurons, which was associated with
      worsened neurobehavioral abnormalities among animals infected with the copassaged
      viruses. Dual lentivirus infections caused an escalation in neuroinflammation and
      ensuing neurodegeneration, underscoring the contribution of infection by multiple
      viruses to neuropathogenesis.

PMID- 19115136
TI  - In vitro antifungal activities of luliconazole, a new topical imidazole.
AB  - Luliconazole is a topical antifungal drug newly developed in Japan. The present
      study compares the in vitro antifungal activity of luliconazole against
      clinically important dermatomycotic fungi with that of other representative
      antifungal drugs. The reference drugs chosen were five classes of nine topical
      agents, i.e., allylamine (terbinafine), thiocarbamate (liranaftate), benzylamine
      (butenafine), morpholine (amorolfine), and azole (ketoconazole, clotrimazole,
      neticonazole, miconazole and bifonazole). The minimum inhibitory concentrations
      (MIC) of luliconazole and the reference drugs against Trichophyton spp. (T.
      rubrum, T. mentagrophytes and T. tonsurans) and Candida albicans were measured by
      the standardized broth microdilution method. Luliconazole demonstrated greater
      potency against Trichophyton spp. (MIC range: <or=0.00012-0.002 microg/ml) than
      the reference drugs, with T. rubrum being the most susceptible to it.
      Luliconazole was also highly active against Candida albicans (MIC range: 0.031
      0.13 microg/ml), proving to be more potent than terbinafine, liranaftate,
      butenafine, amorolfine, and bifonazole, but less than ketoconazole, clotrimazole,
      neticonazole, and miconazole. Further, the MIC of luliconazole against Malassezia
      restricta, an important pathogenic agent involved in seborrhoeic dermatitis, was
      very low (MIC range: 0.004-0.016 microg/ml) suggesting action comparable to or
      stronger than that of ketoconazole. These results indicate a possible clinical
      role for luliconazole with its broad-spectrum antimycotic activity.

PMID- 19115137
TI  - In vitro susceptibility of dermatophytes to conventional and alternative
      antifungal agents.
AB  - The minimum inhibitory concentrations (MICs), the minimal fungicidal
      concentrations (MFCs), the fungal biomass (FB) and hyphal viability employing the
      dye 3-4,5 dimethyl- 2-thiazolyl- 2,5- diphenyl- 2H tetrazolium bromide (MTT) were
      used to compare the in vitro effects of fluconazole (FLU) with those of the N
      terminal palmitoyl-lipidated peptide, Pal-Lys-Lys-NH(2) (PAL), and a tea tree oil
      component, gamma-Terpinene (TER), against several clinical isolates of
      Microsporum canis and Trichophyton rubrum. In general, FLU and PAL MICs were
      significantly lower than those observed with TER, while no differences in the
      three drugs were found in the MFCs. However, they were from two to 16-times
      higher than their respective MICs. FB of M. canis treated with either FLU or PAL,
      but not with TER, was significantly reduced over untreated controls. Only PAL and
      TER, in a medium-dependent fashion, but not FLU, reduced the FB of T. rubrum.
      Finally, PAL was found to be significantly more active than FLU at reducing the
      hyphal viability against both genera of dermatophytes. This study shows that PAL
      exerts an in vitro activity against dermatophytes at least similar to that
      observed with FLU and suggests that this compound might be a promising candidate
      in the treatment of infections due to dermatophytes.

PMID- 19115138
TI  - In vitro activity of antifungal drugs against Cladophialophora species associated
      with human chromoblastomycosis.
AB  - The antifungal activity of six drugs was evaluated against 41 clinical and
      environmental isolates of Cladophialophora carrionii and its sister species C.
      yegresii. Drugs tested, including their ranges, were: 16-0.016 microg/ml for
      amphotericin B (AMB), itraconazole (ITZ) and voriconazole (VCZ), 8-0.008
      microg/ml for terbinafine (TBF), and 64-0.063 microg/ml for flucytosin (5-FC) and
      fluconazole (FCZ). Strains were tested according to the CLSI guidelines (M38A).
      The MIC Gmeans for clinical strains in microg/ml were; 0.02 for TBF and ITZ, 0.07
      microg/ml for VCZ, 0.49 for 5FC, 6.14 for FCZ and 9.42 for AMB. The MFC Gmeans in
      microg/ml were; 0.04 for TBF, 0.13 for ITZ, 0.72 for VCZ, 18.83 for 5FC, 36.16
      for FCZ and 31.35 for AMB. The most active drugs against the fungi were TBF, ITZ,
      VCZ and 5FC. However, for all drugs more than two dilution steps were noted
      between the MIC and the MFC, indicating fungistatic activity. Despite in vitro
      susceptibility of C. carrionii to antifungal agents, the efficacy of therapy was
      shown to be not optimal.

PMID- 19115139
TI  - Platelet-mediated enhancement of leukocyte adhesion.
AB  - Recruitment of inflammatory cells in the perivascular tissue is a necessity for
      many physiological processes. While the inflammatory influx of cells to combat
      infection near the entrance site of infective agents is protective, it also
      drives the development of diseases, such as atherosclerosis. We know from the
      multistep model that cellular recruitment consists of overlapping sequences
      initiated by capturing and rolling of the cell, followed by adhesion, which is of
      paramount importance and indispensable for the subsequent transendothelial
      migration. The spectrum of molecules and cells involved in these processes is
      vast. Platelets have evolved in several ways as amplifiers of leukocyte adhesion,
      since beyond their central role in primary hemostasis, their repertoire of
      adhesion molecules and soluble mediators renders them important interplayers
      between endothelial cells and blood-borne immune cells.

PMID- 19115140
TI  - Phosphotyrosine-dependent in vitro reconstitution of recombinant LAT-nucleated
      multiprotein signalling complexes on liposomes.
AB  - Numerous cell surface receptors propagate activation signals to the interior of
      the cell via tyrosine phosphorylation of transmembrane proteins. This leads to
      the phosphotyrosine (PiY)-mediated recruitment of cytoplasmic signalling protein
      complexes which catalyze crucial biochemical signalling reactions. Here we
      describe the first in vitro reconstitution of such PiY-nucleated protein
      complexes on an artificial lipid membrane. A tyrosine phosphorylated recombinant
      variant of the transmembrane adaptor protein Linker for Activation of T cells
      (PiYLAT) was anchored in liposomes. These PiYLAT proteoliposomes specifically
      recruited cooperative high avidity signalling protein complexes from Jurkat
      cytosol. Nucleation of signalling protein assemblies readily occurred on PiYLAT
      liposomes composed of phosphatidylserine, but not on PiYLAT liposomes composed of
      phosphatidylcholine. Purified recombinant grb2 alone did not stably associate
      with tyrosine phosphorylated LAT proteoliposomes. However, when grb2 was
      presented to the PiYLAT proteoliposomes in the context of Jurkat cytosol it was
      incorporated into multiprotein signalling complexes. Together the data suggest
      that these reconstituted high-avidity signalling protein complexes represent a
      cooperative protein network. This novel in vitro approach offers a novel
      technology permitting biochemical, structural, and pharmacological analyses of
      plasma membrane receptor signalling complexes.

PMID- 19115141
TI  - Deciphering soluble and membrane protein function using yeast systems (Review).
AB  - Membrane protein-protein interactions are important for regulation, targeting,
      and activity of proteins in membranes but are difficult to detect and analyse.
      This review covers current approaches to studying membrane protein interactions.
      In addition to standard biochemical and genetic techniques, the classic yeast
      nuclear two-hybrid system has been highly successful in identification and
      characterization of soluble protein-protein interactions. However, classic yeast
      two-hybrid assays do not work for membrane proteins because such yeast-based
      interactions must occur in the nucleus. Here, we highlight recent advances in
      yeast systems for the detection and characterization of eukaryote membrane
      protein-protein interactions. We discuss these implications for drug screening
      and discovery.

PMID- 19115143
TI  - Protein acyl thioesterases (Review).
AB  - Many proteins are S-acylated, affecting their localization and function. Dynamic
      S-acylation in response to various stimuli has been seen for several proteins in
      vivo. The regulation of S-acylation is beginning to be elucidated. Proteins can
      autoacylate or be S-acylated by protein acyl transferases (PATs). Deacylation, on
      the other hand, is an enzymatic process catalyzed by protein thioesterases (APT1
      and PPT1) but only APT1 appears to be involved in the regulation of the
      reversible S-acylation of cytoplasmic proteins seen in vivo. PPT1, on the other
      hand, is involved in the lysosomal degradation of S-acylated proteins and PPT1
      deficiency causes the disease infant neuronal ceroid lipofuscinosis.

PMID- 19115144
TI  - The fat controller: roles of palmitoylation in intracellular protein trafficking
      and targeting to membrane microdomains (Review).
AB  - The attachment of palmitic acid to the amino acid cysteine via thioester linkage
      (S-palmitoylation) is a common post-translational modification of eukaryotic
      proteins. In this review, we discuss the role of palmitoylation as a versatile
      protein sorting signal, regulating protein trafficking between distinct
      intracellular compartments and the micro-localization of proteins within
      membranes.

PMID- 19115142
TI  - Ras acylation, compartmentalization and signaling nanoclusters (Review).
AB  - Ras proteins have become paradigms for isoform- and compartment-specific
      signaling. Recent work has shown that Ras isoforms are differentially distributed
      within cell surface signaling nanoclusters and on endomembranous compartments.
      The critical feature regulating Ras protein localization and isoform-specific
      functions is the C-terminal hypervariable region (HVR). In this review we discuss
      the differential post-translational modifications and reversible targeting
      functions of Ras isoform HVR motifs. We describe how compartmentalized Ras
      signaling has specific functional consequences and how cell surface signaling
      nanoclusters generate precise signaling outputs.

PMID- 19115145
TI  - Expression of transient receptor potential (TRP) channels in human and murine
      osteoblast-like cells.
AB  - The preservation of bone mass relies on adequate proliferation, differentiation,
      secretion of matrix proteins and rate of apoptosis of the bone-forming
      osteoblasts. Although growing body of evidence indicates that the transient
      receptor potential (TRP) channels play important roles in numerous cellular
      functions, limited information is available about the TRP channels in
      osteoblasts. Here, we inventoried the gene expression and addressed some roles of
      the TRP channels in various osteoblast-like cells. The transcripts of canonical
      TRP (TRPC) channels were revealed for TRPC1, TRPC3, TRPC4 and TRPC6 in human MG
      63, SaOS and U2 OS osteoblasts while transcripts for TRPC2, TRPC4, TRPC6 and
      TRPC7 were observed in the murine MC3T3 osteoblasts. PCR products were shown for
      the melastatin-related TRP (TRPM) channels TRPM4, TRPM6, TRPM7 and TRPM8 in all
      cell lines. The TRPM1 was specifically expressed by murine MC3T3 cells while the
      TRPM3 transcripts were revealed solely in human osteoblast-like cells.
      Transcripts for TRPV2 and TRPV4 were shown in osteoblastic cells. By interfering
      RNA approaches, the TRPC1 channels in osteoblasts were shown to be responsible
      for the capacitative calcium entry (CCE) and for the stimulation of cell
      proliferation by platelet-derived growth factor. On the other hand, interfering
      RNA-mediated abrogation of the expression of TRPM7, known as calcium and
      magnesium channels, resulted in the reduction of both basal and growth factor
      stimulated osteoblastic cell proliferation. Our results provide the first
      complete reference for the gene expression of TRP channels in osteoblasts and
      point to their importance in cell proliferation.

PMID- 19115146
TI  - Protein acylation and localization in T cell signaling (Review).
AB  - Many proteins with pivotal roles in T cell activation are modified by fatty
      acylation. Examples of these include transmembrane proteins such as the co
      receptors CD4 and CD8, the adaptors LAT and Cbp/PAG, the pre-TCR as well as
      proteins synthesized on free cytosolic ribosomes, such as the Src-related
      tyrosine kinases Lck and Fyn. The two main types of fatty acylations in
      eukaryotic cells are N-myristoylation and S-acylation, the latter being more
      commonly referred to as palmitoylation. N-Myristoylation occurs exclusively on
      proteins synthesized on soluble ribosomes and provides substrates with an
      affinity for membranes. Palmitoylation modifies a wide range of substrates that
      includes both cytosolic and transmembrane proteins, its functions are diverse and
      in many cases not yet understood. Like myristoylation, palmitoylation promotes
      membrane-binding of cytosolic proteins, but it has also been implicated in
      protein targeting, trafficking, stability and activity. In addition, many
      palmitoylated proteins are insoluble in cold non-ionic detergent, and have
      therefore been proposed to localize to lipid rafts. The organization of receptors
      and signaling proteins into microdomains such as lipid rafts provides an
      attractive model for the initiation and propagation of T cell signaling, although
      many aspects of this are still poorly understood. This review will discuss the
      current evidence for the involvement of acylations in the localizations and
      functions of T cell signaling proteins.

PMID- 19115147
TI  - Low prevalence of Barrett esophagus in Turkey.

PMID- 19115148
TI  - Low prevalence of erosive esophagitis and Barrett esophagus in a tertiary
      referral center in Turkey.
AB  - BACKGROUND/AIMS: The purpose of upper gastrointestinal endoscopy in
      gastroesophageal reflux disease is to detect the complications; both Barrett
      esophagus and erosive esophagitis are common in developed countries. We aimed to
      investigate the ratio of esophageal complications in gastroesophageal reflux
      disease and the relationship between reflux symptoms and erosive esophagitis.
      METHODS: Six hundred forty-five consecutive adult patients presenting to the
      Reflux Outpatient Clinic were evaluated prospectively. One hundred sixty patients
      who underwent upper gastrointestinal endoscopy and who complained of heartburn or
      regurgitation occurring at least weekly were selected. The complaints and general
      features of patients were queried via a detailed questionnaire. RESULTS: Twenty
      seven patients (17%) had endoscopic evidence of erosive esophagitis. Barrett
      esophagus was found in 3 patients (2%). Neither esophageal stricture nor
      adenocarcinoma was found. Esophagitis was low grade (grades A and B) in 25 of the
      27 (92%) with erosive esophagitis. Patients with erosive esophagitis consumed
      less alcohol than patients with non-erosive reflux disease. No difference was
      found between the severity of symptoms in patients with erosive esophagitis and
      non-erosive reflux disease. CONCLUSIONS: Barrett esophagus and erosive
      esophagitis were less common compared to the literature although the study was
      conducted in a tertiary reference center for gastroesophageal reflux disease. The
      presence of severe symptoms in gastroesophageal reflux disease is not an
      indication for upper gastrointestinal endoscopy. No impact of Helicobacter pylori
      on the severity of esophagitis or symptoms was shown.

PMID- 19115149
TI  - Outcomes in the management of gastrocolic fistulas: a single surgical unit's
      experience.
AB  - BACKGROUND/AIMS: Gastrocolic fistula has been associated with a variety of
      diseases. Causative factors are most commonly gastric/colonic cancers and benign
      gastric ulcers. Treatment modalities may change according to etiology. METHODS:
      In this study, we present our cases with gastrocolic fistula and the treatment
      modalities utilized for this uncommon complication. The records of the patients
      with gastrocolic fistula between November 1996 and June 2006 were retrospectively
      analyzed. RESULTS: Six patients with a mean age of 57.5 were determined. Of
      these, four had malignancy and two had gastric ulcer. The predominant symptoms
      were diarrhea and vomiting, weight loss, and abdominal pain. Diagnostic studies
      included barium enema, endoscopy, barium meal, colonoscopy, and computed
      tomography. After preoperative nutritional support, en-bloc resection of the
      involved gastrocolic region (4), simple excision (1), and wedge resection of the
      gastric part and closure of the colonic wall (1) were performed. One patient died
      of respiratory disorders and there was only one recurrence. In our series,
      therapeutic management for this unusual disorder included various resection
      procedures such as simple excision, which may result in recurrence, and wedge
      resection or en-bloc resection for benign cases, whereas en-bloc resection and
      reconstruction procedures remained the most applied management for malignant
      cases. En-bloc resection followed by combination of adjuvant chemotherapy results
      in long disease-free survival. CONCLUSION: Gastrocolic fistula should be
      suspected in patients with chronic diarrhea and vomiting of unknown cause with a
      high suspicion of gastrointestinal malignancy.

PMID- 19115150
TI  - The effect of decrease in serum nitric oxide concentration on portal hemodynamics
      after Helicobacter pylori treatment: an open-label pilot study.
AB  - BACKGROUND/AIMS: Helicobacter pylori-induced gastritis increases serum nitrate
      and nitrite concentrations. The relationship between splanchnic hemodynamics and
      nitrate and nitrite levels has been demonstrated. We aimed to determine the
      effect of Helicobacter pylori eradication treatment on portal hemodynamics.
      METHODS: Nineteen patients with liver cirrhosis and Helicobacter pylori gastritis
      were included. Nine patients had esophageal varices indicating over portal
      hypertension. After histopathologic examination of gastric mucosa, Doppler
      ultrasonographic measurement of the portal veins and serum sampling to determine
      nitrate and nitrite concentration, treatment for Helicobacter pylori eradication
      was initiated for each patient. Evaluation of histopathology, Doppler
      measurements and sampling for serum nitrate and nitrite levels were repeated six
      weeks after the end of therapy. RESULTS: The rate of eradication of Helicobacter
      pylori was 73.7%. The median inflammation score, Helicobacter pylori density, and
      the median serum concentration of nitrate and nitrite decreased significantly
      after therapy (p values were 0.021, 0.001, and 0.018, respectively). After
      treatment, the patients with varices showed significant decreases in serum
      nitrate and nitrite levels whereas those without varices did not. Considering
      portal measurements, alteration in the congestion index approached statistical
      significance (0.15 versus 0.1; p=0 .066) in the patient group with varices.
      CONCLUSIONS: Reducing effect of Helicobacter pylori eradication treatment on
      serum nitrate and nitrite concentration seems to have some beneficial influence
      on portal hemodynamics.

PMID- 19115151
TI  - Detection of point mutations on 23S rRNA of Helicobacter pylori and resistance to
      clarithromycin with PCR-RFLP in gastric biopsy specimens in Mersin, Turkey.
AB  - BACKGROUND/AIMS: Helicobacter pylori infection has a high prevalence and is
      considered an important health problem in Turkey. Unfortunately, an effective
      treatment has not yet been found for the eradication of Helicobacter pylori
      infection, at least in our country. Standard therapies recommended for the
      eradication of Helicobacter pylori have failed in the province of Mersin, Turkey.
      The rate of eradication with the standard triple treatment was only 45% in the
      province of Mersin. It may be that Helicobacter pylori has become resistant to
      antibiotics. Therefore, we aimed to determine the rate of resistance to
      clarithromycin in the province of Mersin. METHODS: The study included 92 patients
      presenting with dyspepsia to the Gastroenterology Clinic of Mersin University
      Medical School and undergoing endoscopy. We obtained gastric biopsy specimens and
      investigated whether Helicobacter pylori was present and resistant to
      clarithromycin. We used polymerase chain reaction-restriction fragment length
      polymorphism to determine A2143G and A2144G mutations and resistance to
      clarithromycin. RESULTS: Out of 92 specimens, 37 (40.2%) had Helicobacter pylori
      DNA. Out of 37 specimens with Helicobacter pylori DNA, 15 (40.5%) had point
      mutations. Eleven specimens (29.7%) had mutations on nucleotide 2144 and 4
      specimens (10.8%) had mutations on 2143. CONCLUSIONS: Taking account of the
      failure of the treatment regimens used to eradicate Helicobacter pylori infection
      in the province of Mersin, the high rate of point mutations determined in this
      study was not surprising and the rate of resistance to clarithromycin was an
      important indicator for the failure in the eradication of Helicobacter pylori
      infection.

PMID- 19115152
TI  - Effects of polymorphism in G2677T/A triallelic region of MDR1 gene in Turkish
      patients with inflammatory bowel disease.
AB  - BACKGROUND/AIMS: Crohn's disease and ulcerative colitis are both chronic
      inflammatory disorders of the gastrointestinal tract, the main causes of which
      remain unknown. Crohn's disease and ulcerative colitis are characterized by cell
      mediated immune response against the luminal bacteria. It is suggested that
      expression levels and function of P-glycoprotein, encoded by the MDR1 gene, are
      important for protection of the gut against xenobiotics and bacterial toxins.
      Therefore, the mutations of the MDR1 gene are thought to be related with the
      pathogenesis of inflammatory bowel disease. The aim of this study was to
      investigate the G2677T/A polymorphism in the MDR1 gene in Turkish patients with
      inflammatory bowel disease and a healthy control group. METHODS: In our study,
      the genotypes of endoscopically or histopathologically diagnosed Crohn's disease
      (n: 35; 14 F, 21 M) and ulcerative colitis (n: 82; 36 F, 46 M) patients and of 70
      healthy individuals (39 F, 31 M) were compared. In the patient and control
      groups, polymerase chain reaction restriction fragment length polymorphism
      analysis was performed for two polymorphisms (G2677T and G2677A) of the MDR1
      gene. RESULTS: In this study, the frequency of alleles at position 2677 of the
      MDR1 gene, which has a triallelic polymorphism, was not found to be significantly
      different between the patient and the healthy control groups. Moreover, the 2677A
      allele was not detected in either the patient group or the healthy control group.
      CONCLUSIONS: In this study, the G2677T/A polymorphism observed in the MDR1 gene
      was not found to be a risk factor for Crohn's disease or ulcerative colitis.

PMID- 19115153
TI  - Alverine citrate plus simethicone reduces cecal intubation time in colonoscopy -
      a randomized study.
AB  - BACKGROUND/AIMS: Successful colonoscopy depends on the insertion of the
      instrument to the cecum, a detailed examination, and minimal discomfort to the
      patient during the procedure. The aim of this study was to determine the effects
      of alverine citrate plus simethicone on the cecal intubation time, colonic spasm
      and bowel cleanliness. METHODS: A prospective, randomized, controlled trial in a
      consecutive series of patients was conducted to compare alverine citrate as an
      antispasmodic agent for relaxation of spasm with elective colonoscopy. The drug
      used consisted of 60 mg alverine citrate plus 300 mg simethicone. Sodium
      phosphate soda and enema were recommended for bowel cleansing. During
      colonoscopy, spasticity, difficulty of the procedure, pain, and cleanliness of
      the colon were scored between 0-4. The time required to reach the cecum was
      recorded as minutes. RESULTS: Of 165 total patients, 83 and 82 patients were
      randomized as the drug group (mean age: 51.85+/-13.47 years) and control group
      (mean age: 51.68+/-16.28 years), respectively. There was a statistically
      significant difference between the groups in the mean time to reach the cecum in
      favor of the drug group (7.48+/-3.45 minutes vs. 6.20+/-3.24 minutes; p=0.02).
      The time to reach the cecum prolonged with an increase in pain score and
      difficulty score (p=0.0001 and p=0.001, respectively). CONCLUSIONS: Alverine
      citrate plus simethicone reduced the intubation time significantly by 19%, from
      7.48 minutes to 6.20 minutes.

PMID- 19115154
TI  - Giant leiomyoma of the esophagus: a case report and review of the literature.
AB  - Although leiomyoma is the most common esophageal mesenchymal neoplasm, it is a
      rare condition. Resection of the tumor is recommended in symptomatic patients,
      and observation is recommended in asymptomatic patients with small lesions. We
      discuss herein a patient admitted to our outpatient clinic for dyspepsia in whom
      a giant annular esophageal leiomyoma was diagnosed. Resection through
      thoracoabdominal approach is recommended instead of adjuvant treatment in similar
      sized tumors.

PMID- 19115156
TI  - Midgut volvulus: value of multidetector computed tomography in diagnosis.
AB  - Midgut volvulus is a rare complication of intestinal malrotation in adults. We
      present a case of intestinal malrotation with surgically proven midgut volvulus.
      Multidetector computed tomography with postprocessing of imaging data using three
      dimensional reconstruction techniques provided better demonstration of the
      abdomen than other imaging modalities. To our knowledge, this is the first
      presentation of midgut volvulus on multidetector computed tomography in adults.
      The literature on midgut volvulus is also reviewed and imaging findings of this
      disease are discussed.

PMID- 19115155
TI  - Granular cell tumor of the esophagus: three case reports and review of the
      literature.
AB  - The esophagus is the most common site of origin of gastrointestinal tract
      granular cell tumors. Approximately 270 cases of esophageal granular cell tumors
      have been reported in the literature. Most esophageal granular cell tumors are
      found incidentally during endoscopy. Although granular cell tumor of the
      esophagus has become easily recognizable by its endoscopic features, it has to be
      differentiated from other benign and malignant mucosal and submucosal lesions.
      The majority of esophageal granular cell tumors are asymptomatic and benign;
      thus, close follow-up of the patients with endoscopy could be considered
      sufficient as a therapeutic management. New therapeutic options should be
      considered especially for larger lesions. Three cases of granular cell tumors
      with complaints of epigastric discomfort, regurgitation, nausea, and vomiting,
      which were detected in the lower part of the esophagus on upper gastrointestinal
      tract endoscopy, are discussed with the most recent literature review on this
      subject.

PMID- 19115157
TI  - Synchronous endocrine tumors of small intestine: report of a case.
AB  - As with most endocrine tumors, the malignant potential depends on evidence of
      local or distant invasion (metastasis), so it is important to differentiate
      synchronous/metachronous endocrine tumors from their metastases. A 90-year-old
      man was operated due to tumor of the ampulla of Vater. As the surgical specimen
      was examined macroscopically, a second tumor focus, measuring 1 cm in diameter,
      was detected at the duodenum. There were no clinical syndromes due to hormone
      hypersecretion. Microscopically, the ampullary tumor had trabecular and rosette
      like patterns, with many necrotic areas. It had invaded the muscularis mucosa at
      the duodenal wall. The latter duodenal tumor was located in the submucosa and had
      distinct borders. This tumor consisted of trabecular structures with stroma rich
      in lymphoid aggregates. Immunohistochemistry revealed positivity for
      synaptophysin and gastrin and negativity for somatostatin. In addition, the whole
      antral portion of the Whipple resection material showed diffuse parietal cell
      hyperplasia. The tumors were diagnosed as well-differentiated endocrine carcinoma
      in the ampulla of Vater according to the WHO classification 2000, a gastrin
      producing well-differentiated endocrine tumor in the first portion of the
      duodenum without regional lymph node metastases, and a diffuse parietal cell
      hyperplasia at the antral portion of the stomach. In conclusion, clinical
      findings and the postoperative diagnosis suggest that this patient had primary
      synchronous neuroendocrine tumors of the small intestine.

PMID- 19115158
TI  - Infliximab treatment of massive upper gastrointestinal bleeding in gastroduodenal
      Crohn's disease.

PMID- 19115159
TI  - Prevalence of appendectomy and tonsillectomy in patients with inflammatory bowel
      disease: a case-control study.

PMID- 19115160
TI  - A transverse colonic mass secondary to Actinomyces infection mimicking cancer.

PMID- 19115161
TI  - Elevations of serum aminotransferase in muscular dystrophy.

PMID- 19115162
TI  - Pleural effusion: always innocent?

PMID- 19115163
TI  - A case report of highly suspected ciprofloxacin-induced hepatotoxicity.

PMID- 19115164
TI  - Evaluation of intracranial aneurysms with 7 T versus 1.5 T time-of-flight MR
      angiography - initial experience.
AB  - PURPOSE: The purpose of this study was to compare the depiction of intracranial
      aneurysms by 3D time-of-flight (TOF) magnetic resonance angiography (MRA) at 7
      Tesla (T) with the clinical standard TOF MRA at 1.5 T and with digital
      subtraction angiography (DSA). MATERIALS AND METHODS: 7 T and 1.5 T TOF MRA
      images optimized for both field strengths were compared in ten patients with an
      unruptured intracranial aneurysm. Two blinded neuroradiologists independently
      rated the image quality of the dome, the neck, and the vessel of origin of all
      aneurysms in MRA source and maximum intensity projection (MIP) images. DSA was
      obtained in all subjects and served as reference standard. The mean values of
      image quality were compared by Wilcoxon signed rank test. In all patients the
      number and location of the aneurysms was confirmed by DSA. RESULTS: Both readers
      identified twelve aneurysms in ten patients in 7 T, 1.5 T TOF MRA and DSA. The
      image quality of the aneurysm dome was rated higher in 8 of 12 aneurysms and the
      image quality of the aneurysm neck was superior in 9 of 12 aneurysms at 7 T TOF
      MRA compared to 1.5 T TOF MRA. The depiction of the parent vessel was graded
      almost equally by both readers. CONCLUSION: Our initial results indicate that
      image quality of intracranial aneurysms may benefit from the increased spatial
      resolution of 7 T TOF MRA compared with 1.5 T TOF MRA. Tailored scan protocols
      and optimized radiofrequency head coils are needed to further improve the image
      quality of 7 T TOF MRA.

PMID- 19115165
TI  - [Compression of digital images in radiology - results of a consensus conference].
AB  - PURPOSE: Recommendations for lossy compression of digital radiological DICOM
      images in Germany by means of a consensus conference. The compression of digital
      radiological images was evaluated in many studies . Even though the results
      demonstrate full diagnostic image quality of modality-dependent compression
      between 1:5 and 1:200, there are only a few clinical applications. MATERIALS AND
      METHODS: A consensus conference with approx. 80 interested participants
      (radiology, industry, physics, and agencies) without individual invitation was
      organized by the working groups AGIT and APT of the German Roentgen Society DRG
      to determine compression factors without loss of diagnostic image quality for
      different anatomical regions for CT, CR/DR, MR, RF/XA examinations. The consent
      level was specified as at least 66 %. RESULTS: For individual modalities the
      following compression factors were recommended: CT (brain) 1:5, CT (all other
      applications) 1:8, CR/DR (all applications except mammography) 1:10, CR/DR
      (mammography) 1:15, MR (all applications) 1:7, RF/XA (fluoroscopy, DSA, cardiac
      angio) 1: 6. The recommended compression ratios are valid for JPEG and JPEG 2000
      /Wavelet compressions. CONCLUSION: The results may be understood as
      recommendations and indicate limits of compression factors with no expected
      reduction of diagnostic image quality. They are similar to the current national
      recommendations for Canada and England .

PMID- 19115167
TI  - Neurological consultation in the ICU.

PMID- 19115168
TI  - Preoperative evaluation of patients with neurological disease.
AB  - A thorough evaluation of patients with neurological diseases undergoing surgery
      can reduce perioperative morbidity and mortality, especially stroke. Various
      neurological disorders and neurosurgical procedures may influence the nature and
      extent of preoperative evaluation, selection and conduct of anesthesia, and
      perioperative management and care. Although anesthesiologists primarily perform a
      preoperative evaluation of neurological patients, neurologists can contribute
      further valuable information about the neurological condition and perioperative
      management of various neurological diseases to obtain the best possible outcome.
      This article outlines the basic elements of preoperative evaluation and
      highlights specific considerations for neurological patients undergoing surgery.

PMID- 19115169
TI  - Sedation and pain management in acute neurological disease.
AB  - The optimum provision of pharmacological sedation of the critically ill
      neurological patient requires defining the underlying etiology of agitation or
      need for sedation to determine the optimal agent: pain management, anxiolysis, or
      treatment of delirium. An appropriate regimen can then be decided upon based on
      the profiles of action of the several common classes of sedative agents. Methods
      to both evaluate the efficacy of sedation as well as titration to a predefined
      clinical goal are important tools toward safe administration of drugs that often
      have serious adverse effects. Recognition of an individualized approach is also
      necessary as patients will vary considerably with respect to the kinetics and
      pharmacodynamics of sedative therapy. The drug classes often selected for
      sedation in an intensive care unit will be reviewed as well as the metrics by
      which physicians can achieve their objectives in a safe manner.

PMID- 19115170
TI  - Brain imaging in intensive care medicine.
AB  - The management of severe brain injury requires a comprehensive approach in which
      imaging is an indispensable complement to the clinical and physiological
      information acquired at the bedside. Neuroimaging methods are routinely used in
      the diagnosis and prognosis of a broad spectrum of patients with acute
      neurological dysfunction. With incremental theoretical and technological
      refinements, imaging modalities are helping to unravel fundamental questions
      regarding the pathophysiology and neuroplasticity associated with critical
      neurological injury, and it is anticipated that this knowledge will lead to new
      and effective therapeutic interventions. We review some of the established and
      emerging structural and physiological imaging methods, and discuss their
      applications in patients with critical injuries including trauma and
      encephalopathy due to anoxia, liver failure, and sepsis.

PMID- 19115171
TI  - Ischemic stroke and ICU care.
AB  - Acute ischemic stroke is a common disorder with a significant impact on morbidity
      and mortality in the United States. The number of interventions for acute stroke
      patients has increased over the past 15 years and patients increasingly require
      intensive care. There are several issues that are specific to ischemic stroke
      patients in intensive care unit (ICU) settings, including the care of the
      postthrombolytic stroke patient, respiratory issues in stroke care, evaluation of
      worsening or change in neurological status, and attention to factors that affect
      the ischemic penumbra. The management of the stroke patient in the critical care
      setting is discussed in this article.

PMID- 19115172
TI  - Intracerebral hemorrhage.
AB  - Intracerebral hemorrhage (ICH) accounts for 10 to 15% of all strokes, but results
      in a disproportionately high morbidity and mortality. Although chronic
      hypertension accounts for the majority of ICH, other common causes include
      cerebral amyloid angiopathy, sympathomimetic drugs of abuse, and underlying
      cerebral vascular anomalies. Validated baseline predictors of clinical outcome
      after ICH include the Glasgow Coma Scale score, hematoma volume, presence and
      amount of intraventricular hemorrhage, infratentorial ICH location, and advanced
      age. Although no treatment of proven benefit currently exists for ICH, several
      recent large clinical trials have demonstrated the feasibility of surgical and
      medical treatments for ICH. Clinical research into ICH mechanisms of injury has
      demonstrated that hematoma expansion is common, even in patients without
      coagulopathy. Basic research has suggested that perihematoma injury is more
      likely related to toxicity of blood and iron in the brain
      ("neurohemoinflammation") rather than primary ischemic injury. Current guidelines
      for ICH treatment emphasize blood pressure management, urgent and rapid
      correction of coagulopathy, and surgery for cerebellar ICH. Ongoing clinical
      trials are investigating surgical evacuation of lobar hemorrhage, minimally
      invasive surgical hematoma evacuation, and aggressive blood pressure lowering.

PMID- 19115173
TI  - Seizures and status epilepticus in the intensive care unit.
AB  - Persistent seizures and failure to regain consciousness following witnessed
      seizure activity require emergency neurological consultation. Although outcome is
      largely dependent on underlying cause, early maximal anticonvulsant therapy is
      critical to reducing morbidity. This review covers important concepts in the
      clinical and EEG diagnosis of status epilepticus, and discusses treatment
      algorithms for single and recurrent seizures, emphasizing the need to rationalize
      therapy depending on the presumed duration of seizure activity. The review takes
      the perspective of the neurological consultant in the intensive care unit, and
      considers all pharmacological approaches available to the intensivist as
      described in the current literature and from clinical experience.

PMID- 19115174
TI  - Central nervous system infections in the intensive care unit.
AB  - Infections of the central nervous system are a frequent cause for admission to
      the intensive care unit (ICU). These infections can be the reason for
      presentation to a hospital or a complication of an injury or surgical procedure.
      Diagnosing these infections can be very challenging, given the relative paucity
      of tests with high sensitivity and specificity. Regardless, identifying and
      treating the underlying cause remains the primary objective in each of these
      cases, but management of complications is the most common reason for ICU
      admission. Frequent complications include increased intracranial pressure,
      stroke, coma, and status epilepticus. Although the underlying infection often
      causes harm, the immune response to the agent and ensuing complications are often
      responsible for greater damage to the host. Even if the underlying infectious
      agent does not have a specific therapy, identifying it is important for limiting
      unnecessary testing. When certain infections are suspected, such as bacterial
      meningitis or viral encephalitis, empiric therapy should be initiated
      immediately. Outcomes for these conditions are linked to how quickly appropriate
      therapies are initiated.

PMID- 19115175
TI  - Intracranial hypertension.
AB  - Intracranial hypertension implies profoundly disturbed intracranial physiology.
      Although a shared manifestation of myriad neurological disorders of patients
      admitted in the intensive care unit (ICU), the pathways leading to intracranial
      hypertension vary by etiology. Acute elevation of the intracranial pressure is an
      emergency and may rapidly lead to brain death or a devastating neurological
      outcome if left untreated. Fortunately, with a firm grasp of the underlying
      pathophysiology and available treatments, one can optimize ICU-based management.
      Several integrated management paradigms have been used to treat intracranial
      hypertension. Regrettably, there is a dearth of randomized clinical trials to
      confirm the efficacy of even our most routine therapeutic strategies.

PMID- 19115177
TI  - Autonomic complications following central nervous system injury.
AB  - Severe sympathetic overactivity occurs in several conditions that are recognized
      as medical emergencies. Following central nervous system injury, a small
      proportion of individuals develop severe paroxysmal sympathetic and motor
      overactivity. These individuals have a high attendant risk of unnecessary
      secondary morbidity. Following acquired brain injury, the syndrome is known by a
      number of names including dysautonomia and sympathetic storm. Dysautonomia is
      currently a diagnosis of exclusion and often goes unrecognized. The evidence base
      for management is almost entirely anecdotal in nature; there has been little
      structured or prospective research. In contrast, the evidence base for autonomic
      dysreflexia following spinal cord injury is much stronger, with level 1 evidence
      for many treatment interventions. This review presents a current understanding of
      each condition and suggests simple management protocols. With the marked
      disparity in the literature for the two conditions, the main focus is on the
      literature for dysautonomia. The similarity between these two conditions and the
      other autonomic emergency conditions is discussed.

PMID- 19115178
TI  - Withdrawal of life-sustaining therapies and brain death in the intensive care
      unit.
AB  - The majority of patients who die in intensive care units (ICUs), do so as a
      result of the withdrawal of life-sustaining treatments or as a result of brain
      death. With the increasing shortage of transplantable organs, there is growing
      interest in both these patient populations and their potential for organ donation
      after cardiac death (DCD) or death by neurological criteria. Therefore, it is
      imperative for neurologists and neurosurgeons to be familiar with both processes
      when consulted to evaluate these very sick patients in the ICU. The medicolegal
      and ethical considerations, the factors that lead to the decision for withdrawal
      (with special attention to prognostication of the major neurological diseases
      encountered in an ICU), the process of withdrawal of life-sustaining treatment
      itself, and the DCD process will be examined. The medicolegal aspects of brain
      death will also be examined, with particular focus on the process and the various
      pitfalls and misconceptions.

PMID- 19115179
TI  - [Long-term outcome of children with intrauterine detected increased nuchal
      translucency].

PMID- 19115180
TI  - [Rehabilitation of the benign oesophageal stenosis in childhood].

PMID- 19115176
TI  - Neurological complications of cardiac surgery.
AB  - Neurological injury resulting from cardiac surgery has a range of manifestations
      from focal neurological deficit to encephalopathy or coma. As the safety of drug
      eluting stents comes into question, more patients will likely undergo coronary
      artery bypass graft surgery. These projections, along with the growing
      proportions of elderly patients and those with comorbidities, portend the
      potential for rising rates of perioperative neurological complications. The risk
      for neurological injury may be determined by the type of procedure, by patient
      specific characteristics, and by the extent of cerebral embolization and
      hypoperfusion during and after surgery. Changes in surgical techniques, including
      the use of off-pump surgery, have not decreased rates of brain injury from
      cardiac surgery. When appropriate, modern neuroimaging techniques should be used
      in postoperative patients to confirm diagnosis, to provide information on
      potential etiology, to direct appropriate therapy, and to help in
      prognostication. Management of postoperative medications and early use of
      rehabilitation services is a recommended strategy to optimize the recovery for
      individuals with neurological injury after cardiac surgery.

PMID- 19115181
TI  - [Double tracheo-oesophageal fistula, oesophageal atresia, and tracheal stenosis-
      an exceptional tracheoscopic view].
AB  - This report highlights the diagnostic and therapeutic challenges which occurred
      in a newborn with oesophageal atresia of the type Vogt III c in association with
      a tubular supracarinal tracheal stenosis.

PMID- 19115182
TI  - [Principles and risks of electrosurgery].
AB  - Electrosurgical instruments are routinely used in many applications by the
      surgeon. In principle, high-frequency electrical currents are used by passing
      trough tissue for cutting and coagulation. The heat generated by the
      electrosurgical unit is proportional to the resistance and diameter of the
      tissue. There are two commonly used electrosurgical modalities: monopolar and
      bipolar. Since negative side-effects of electrosurgery are possible (e.g. burn,
      interaction with other electric devices) a proper knowledge of all staff involved
      in electrosurgery is warranted. In the context of a safe perioperative patient
      management the anesthesiologist should know basic principles of high-frequency
      surgery as well. This article describes the main aspects of electrosurgery for
      anesthesiologists.

PMID- 19115183
TI  - [Substance-abuse related emergencies--illegal drugs, part II].
AB  - For the first time since the year 2000 the number of death due to substance abuse
      of illegal drugs has increased in Germany in 2007 (+8 % compared to 2006).
      Emergency situations due to drug abuse are frequent, particular in big cities.
      They may be, however, difficult to diagnose and / or treat for an emergency
      physician on scene because of a lack of diagnostic tools, the local and personal
      surroundings, and the unknown number and nature of drugs. Many drug intoxications
      must be considered suicidal. On the other hand, drug intoxications may mask
      (other) life-threatening conditions. Emergency situations due to withdrawal offer
      the possibility to motivate patients to take advantage of specialist-guided
      abstinence programs.

PMID- 19115184
TI  - [Preclinical use of intraosseous access (IO) in adults: literature review and
      case reports].
AB  - The treatment of acute life threatening conditions normally requires intravenous
      access for further therapeutic measures. In the current guidelines of the
      European Resuscitation Council (ERC), published in November 2005, the
      significance of intraosseous access had been newly regulated. Nevertheless two
      years after publication of these guidelines, intraosseous acccess in adults is
      still only implemented sporadically. The translation of scientific knowledge into
      clinical practise takes several years as a general rule. The following article
      illustrates the basic literature and two case reports, and is designed to inspire
      trust in a method, which can provide a useful alternative to peripheral venous
      access for the emergency physician.

PMID- 19115185
TI  - [The dirty dozen].
AB  - The term "the dirty dozen" refers to the 12 biological agents such as, for
      example, the anthrax bacillus or botulinum toxin that could be used as biological
      weapons. Even if their military use is considered unlikely physicians should be
      familiar with the problematic because these pathogens can also occur naturally
      or, respectively, cause disease as the consequence of a laboratory accident. It
      is of decisive importance to make the diagnosis as quickly as possible in order
      to limit any further spread of the disease.

PMID- 19115186
TI  - [Chronic back pain---clear therapy options as opposed to diffuse symptoms].

PMID- 19115187
TI  - [Radiological differential diagnosis of chronic back pain].
AB  - Back pain is a frequent phenomenon. Published guidelines should be used to avoid
      unnecessary diagnostic imaging ("European guidelines for the management of
      chronic non-specific low back pain" - www.backpaineurope.org). Frequent
      degenerative changes and their correlation to acute and chronic back pain are
      described in the following text. Inflammation and tumour caused spine disease
      need special attention. A false choice of imaging procedure could delay the
      correct diagnosis.

PMID- 19115188
TI  - [Chronic low back pain--need for an interdisciplinary approach].
AB  - Low back pain is a burden in health policy and medical care. One of the main
      problems in that field comes from the fact that a minor part of all patients
      developchronic pain; those claiming for the main part of all costs. The
      transition from acute to chronic pain is dominated by psychological factors and
      there is a strong need to identify them at a very early stage of the illness.
      Concerning diagnostic procedures it is at first necessary to eliminate red flags.
      Afterwards, treatment is dominated by motivating the patients to intensify their
      daily activities and to inform them about the harmless nature of non-specific
      back pain. In case of chronic pain syndromes there is a strong need for
      interdisciplinary procedures in diagnosis and multiprofessional treatment.
      Multimodal treatment should be modelled on the concept of functional restoration.

PMID- 19115189
TI  - [Chronic back pain--operative therapeutic options in chronic back pain].
AB  - The main challenge in the surgical treatment of chronic low back pain lies in the
      poor knowledge of its etiology. Surgery, however, requires the identification of
      a surgically curable lesion. In cases of radiologically obvious structural spinal
      disease like stenosis, instability or deformity, surgery is indicated after
      failure of conservative measures and achieves acceptable success rates. The vast
      majority of patients, however, demonstrates only unspecific segmental
      degeneration. Fusion is only somewhat effective and there is no evidence-based
      data for the abundant modern and less invasive techniques.

PMID- 19115190
TI  - The times they are a-changing--a year of transition.

PMID- 19115191
TI  - The mechanisms of hyperphosphatemia-induced vascular calcification.
AB  - Extensive calcification of the arterial wall and soft tissues is a frequent
      feature of patients with end-stage chronic kidney disease (CKD stage 5).
      Hyperphosphatemia and secondary hyperparathyroidism have been extensively
      investigated as inducing factors in cardiovascular calcification. In fact,
      cardiovascular disease in renal failure is associated with bone metabolism
      alterations. Together with passive deposition of calcium-phosphate in
      extraskeletal tissues, it has recently been demonstrated that inorganic phosphate
      induces arterial calcification directly through a real "ossification" of the
      tunica media in the vasculature of CKD patients. Therefore, control of serum
      phosphate in CKD patients becomes crucial in preventing increases in calcium x
      phosphate product, secondary hyperparathyroidism, and ultimately vascular
      calcification.

PMID- 19115192
TI  - Transmission of hepatitis C virus infection in hemodialysis: current concepts.
AB  - A variety of epidemiological data provides evidence for the occurrence of
      nosocomial transmission of hepatitis C virus (HCV) infection to hemodialysis (HD)
      patients. The most important factor implicated in HCV transmission between
      patients treated in the same dialysis unit is cross-contamination from supplies
      and surfaces as a result of failure of staff to follow infection control
      procedures. Parts of the HCV genome are highly variable and lend themselves to
      fingerprinting of each isolate using nucleic acid testing (NAT) and sequencing.
      This approach has permitted investigation of possible transmission routes within
      HD units. A systematic review of molecular virology papers revealed transmission
      of HCV via internal fluid pathways of the dialysis machines in a minority of
      reports only. Dialyzer reuse was not identified as a risk factor for HCV
      acquisition in multicenter databases. No randomized controlled trials exist on
      the impact of isolation on the risk of transmission of HCV to hemodialysis
      patients. A Belgian prospective multicenter study showed a reduction from 1.4% to
      0% in the annual incidence of seroconversion for HCV without any isolation
      measures, by implementation of strict infection control procedures designed to
      prevent transmission of blood-borne pathogens, including HCV. However, an
      isolation policy for HCV-infected dialysis patients should be considered in
      dialysis units where nosocomial transmission of HCV persists despite
      reinforcement and audit of hygienic precautions for hemodialysis. Routine audit
      precautions (general and for dialysis machines) are recommended on a regular
      basis within HD units.

PMID- 19115193
TI  - Gene delivery systems for gene therapy in tissue engineering and central nervous
      system applications.
AB  - The present review aims to describe the potential applications of gene delivery
      systems to tissue engineering and central nervous system diseases. Some key
      experimental work has been done with interesting results, but the subject is far
      from being fully explored. The combined approach of gene therapy and material
      science has a huge potential to improve the therapeutic approaches now available
      for a wide range of medical applications. Focus is given to this
      multidisciplinary strategy in neurodegenerative pathologies, where the use of
      polymeric matrices as gene carriers might make a crucial difference.

PMID- 19115194
TI  - Ertapenem clearance during modeled continuous renal replacement therapy.
AB  - PURPOSE: To determine ertapenem transmembrane clearance (CLtm) during continuous
      renal replacement therapy (CRRT) using a validated in vitro model. METHODS:
      Ertapenem clearance during continuous hemofiltration and hemodialysis was
      assessed with AN69 and polysulfone hemodiafilters at 4 dialysate (Qd) and
      ultrafiltration rates (Quf): 1, 2, 3, and 6 l/hour. Blood and dialysate samples
      were collected at each flow rate and assayed for urea (control solute) and
      ertapenem concentrations. The experiment was repeated 5 times for each
      hemodiafilter type. Ertapenem and urea sieving coefficient (SC) and saturation
      coefficient (SA) were assessed, and CLtm calculated. RESULTS: In continuous
      hemofiltration mode, urea and ertapenem SC ranged from 1.00 to 1.19 at all Quf
      and did not differ between hemodiafilter types. Consequently, convective CLtm
      also did not differ between hemodiafilters. In continuous dialysis mode, urea
      Cltm did not differ between hemodiafilter types at any Qd. However, ertapenem SA
      and CLtm were significantly different between hemodiafilter types at Qd 6l/hour
      (p<0.001). As Qd increased, mean +/- SD AN69 SA declined significantly from 0.87
      +/- 0.12 at Qd 1 l/hour to 0.45 +/- 0.02 at Qd 6 l/hour (p<0.001). Ertapenem SA
      did not differ at any Qd with the polysulfone hemodiafilter (range 0.71-0.80).
      CONCLUSION: Ertapenem was cleared substantially in these in vitro CRRT models.
      However, our findings illustrate discordance between our observed SC and SA and
      the published unbound fraction of ertapenem. This finding has been reported with
      many other drugs, including carbapenem antibiotics. If in vivo studies
      corroborate our SA and SC findings, dosage adjustment for patients receiving CRRT
      will be required.

PMID- 19115195
TI  - Application of fuzzy logic to predicting erythropoietic response in hemodialysis
      patients.
AB  - OBJECTIVE: The purpose of this study was to demonstrate how fuzzy sets can be
      used in a pharmacodynamic model to represent the uncertainty about the
      classification of an end-stage renal disease patient's response to
      erythropoietin. METHODS: A pharmacodynamic model was developed to predict future
      hemoglobin response to administered erythropoietin for a population of 186
      patients with end-stage renal failure and anemia. The prediction was performed by
      a weighted linear combination of past hemoglobin, transferrin saturation, and
      erythropoietin dose. Patients were classified based on their response to
      administered erythropoietin into (i) all patients into 1 group (population
      approach), (ii) all patients into either a poor or normal responder group
      (subpopulation approach--traditional classification), and (iii) all patients by
      partial membership into the poor and normal responder groups (subpopulation
      approach--fuzzy classification). One half of the data set was randomly selected
      to estimate the model parameters, and the second half was used to test the
      estimated model. This randomization was repeated 100 times for both males and
      females. RESULTS: Mean square error decreased significantly through the
      incorporation of hemoglobin response categorization from the control group (1.32
      +/- 0.07), to crisp coding (1.23 +/- 0.07), to fuzzy coding (1.20 +/- 0.07) with
      an overall p value < 0.001. CONCLUSION: Uncertainty in the categorization of
      subjects into 2 erythropoietin response groups of poor or normal response has
      been shown to benefit from the use of fuzzy categories, with a significant
      improvement in model performance.

PMID- 19115196
TI  - Application of a user-friendly comprehensive circulatory model for estimation of
      hemodynamic and ventricular variables.
AB  - PURPOSE: Application of a comprehensive, user-friendly, digital computer
      circulatory model to estimate hemodynamic and ventricular variables. METHODS: The
      closed-loop lumped parameter circulatory model represents the circulation at the
      level of large vessels. A variable elastance model reproduces ventricular
      ejection. The circulatory model has been modified embedding an algorithm able to
      adjust the model parameters reproducing specific circulatory conditions. The
      algorithm reads input variables: heart rate, aortic pressure, cardiac output, and
      left atrial pressure. After a preliminary estimate of circulatory parameters and
      ventricular elastance, it adjusts the amount of circulating blood, the value of
      the systemic peripheral resistance, left ventricular elastance, and ventricular
      rest volume. Input variables and the corresponding calculated variables are
      recursively compared: the procedure is stopped if the difference between input
      and calculated variables is within the set tolerance. At the procedure end, the
      model produces an estimate of ventricular volumes and Emaxl along with systemic
      and pulmonary pressures (output variables). The procedure has been tested using 4
      sets of experimental data including left ventricular assist device assistance.
      RESULTS: The algorithm allows the reproduction of the circulatory conditions
      defined by all input variable sets, giving as well an estimate of output
      variables. CONCLUSIONS: The algorithm permits application of the model in
      environments where the simplicity of use and velocity of execution are of primary
      importance. Due to its modular structure, the model can be modified adding new
      circulatory districts or changing the existing ones. The model could also be
      applied in educational applications.

PMID- 19115197
TI  - A novel model for external biliary drainage in rat orthotopic liver
      transplantation.
AB  - OBJECTIVE: The objective of this study was to establish a stable model of
      orthotopic liver transplantation with external biliary drainage in rats, to
      provide the possibility for dynamic detection of bile characteristics after
      transplantation. METHODS: Ninety-eight Sprague Dawley rats were divided randomly
      into a control group (n = 30) and an external drainage group (n = 68). Biliary
      extra-drainage group rats were established as follows: an epidural catheter was
      implanted into the common bile duct and an appropriate hose was connected from
      the outside. A stoma was made into the high jejunum, and a hose was implanted.
      Then the 2 hoses were induced to connect with each other in the subcutis of the
      right lateral abdominal wall. RESULTS: The operative success rate and 1-week and
      2-week survival rates of the extra-drainage group were 94.1% (64/68), 88.2%
      (60/68), and 79.4% (54/68), respectively. Meanwhile, in the control group, the
      operative success rate and 1-week and 2-week survival rates were 93.3% (28/30),
      90% (27/30), and 83.3% (25/30), respectively. There were no significant
      differences at any time between the 2 groups (p > 0.05). CONCLUSIONS: The biliary
      extra-drainage model in rat orthotopic liver transplantation provides a novel,
      simple, and reliable method for dynamic collection of bile. The operation success
      rate was satisfactory. This model was successful and could be applied in various
      experimental studies.

PMID- 19115198
TI  - Hepatic migration of a catheter fragment followed by disconnection of a totally
      implantable venous access port.
AB  - Totally implantable venous access ports (TIVAPs) are frequently used in oncology
      patients who require long-term courses of chemotherapy. We report a silent, but
      potentially hazardous complication of catheter fracture and hepatic migration in
      a 64-year-old male. The patient presented with a painful, rapid swelling of
      subcutaneous tissue around the port area during a saline flush. A chest
      radiograph showed that the disconnected catheter had separated from the port and
      was no longer in its original location. A chest CT scan revealed that the
      disconnected catheter was found to be embolized to the right atrium, inferior
      vena cava and right hepatic vein. The patient was treated successfully with
      percutaneous transfemoral retrieval of the catheter under fluoroscopic guidance.
      To our knowledge, there have been no previous reports of migration of the
      fractured catheter of a TIVAP into the right hepatic vein. This case highlights
      that the integrity of TIVAPs should be ascertained before chemotherapeutic drugs
      are administered.

PMID- 19115199
TI  - Targeting transforming growth factor (TGF)-betaRI inhibits activation of beta1
      integrin and blocks vascular invasion in hepatocellular carcinoma.
AB  - Vascular invasion is one of the major negative prognostic factors in patients
      with hepatocellular carcinoma (HCC), leading to cancer recurrence. To invade, HCC
      cells must penetrate the vessel wall, consisting of endothelial cells and
      extracellular matrix components, including fibronectin and fibrinogen. Employing
      invasive and noninvasive HCC cells, we studied the mechanism underlying vascular
      invasion. We show that HCC cells invade blood vessels via alpha5beta1, that is
      equally expressed in invasive and noninvasive cells. However, in the former, the
      intracytoplasmic tail of beta1 integrin is constitutively phosphorylated at
      threonine 788-789 and the extracellular part is conformationally activated. In
      noninvasive cells, beta1 integrin is not activated. Transforming growth factor
      (TGF)-beta1 specifically phosphorylates beta1 integrin (threonine 788-789) via
      Smad-2 and Smad-3, causing a conformational change of the extracellular component
      with an inside-out mechanism. This leads noninvasive HCC cells to behave like
      invasive cells. A selective TGF-betaRI inhibitor inhibits phosphorylation of the
      beta1 integrin intracytoplasmic tail, and blocks invasion of HCC cells, both
      constitutively invasive and with acquired invasive properties. In human HCC
      tissues with microvascular invasion, phospho-beta1 integrin was detected as well
      as TGF-beta1, p-Smad-2, and E-cadherin. CONCLUSION: TGF-beta1 promotes vascular
      invasion by activating beta1 integrin. This suggests a rationale for targeting
      TGF-betaRI in future clinical trials.

PMID- 19115200
TI  - SOCS3 as a tumor suppressor in breast cancer cells, and its regulation by PRL.
AB  - Suppressor of cytokine signaling 3 (SOCS3), as a key regulator of cytokine
      signaling, has the potential to modulate numerous cellular processes. Its
      involvement in inflammatory disease is well established, and there is increasing
      evidence for a role in breast cancer as a regulator of signal transducers and
      activators of transcription (STATs). Here we show that over-expression of SOCS3
      markedly supresses STAT3 expression, and abrogates STAT5 phosphorylation,
      resulting in decreased cell proliferation in T47D breast cancer cells, and
      decreased proliferation and anchorage-independent growth in MCF7 cells. Using
      T47D cells, we elucidated the signaling pathways and transcription factors
      involved in SOCS3 expression in response to prolactin, a key mammotropic hormone.
      Quantitative real time PCR was used to examine SOCS3 mRNA expression, IP/WB was
      used to examine STAT phosphorylation, luciferase reporter assays, chromatin
      immunoprecipitation (ChIP) and gel shift assays allowed evaluation of cis
      elements and trans-factors regulating SOCS3 expression. We demonstrate that
      prolactin-induced SOCS3 expression is STAT-dependant, predominantly involving
      STAT5, although STAT1 is also associated with the promoter. In addition,
      prolactin-induced SOCS3 promoter activation requires PKA-stimulated Sp1 binding
      to the GC-rich region of the promoter. Finally, we show that PRL-induced SOCS3
      expression can be potentiated by co-treatment with PGE(2). This study
      demonstrates that SOCS3 acts as an anti-proliferative agent in breast cancer
      cells, and highlights the complexity of SOCS3 regulation and crosstalk.

PMID- 19115201
TI  - Response: Risk of prostate, breast and colorectal cancer after skin cancer
      diagnosis.

PMID- 19115202
TI  - Risk of internal cancer after diagnosis of skin cancer depends on latitude,
      smoking status and type of skin cancer.

PMID- 19115203
TI  - Gamma-tocopherol-enriched mixed tocopherol diet inhibits prostate carcinogenesis
      in TRAMP mice.
AB  - Gamma-tocopherol (gamma-T) alone or in combination with alpha-tocopherol has been
      shown to suppress biomarkers of oxidative stress in asthamatics and human
      subjects with metabolic syndrome. Oxidative stress has been implicated as a key
      event in prostate carcinogenesis. Hence, the purpose of this study was to examine
      the effects of gamma-tocopherol-enriched mixed tocopherol diet on prostate
      carcinogenesis in a murine prostate cancer model (TRAMP). 8 week old TRAMP males
      were fed 0.1% gamma-T-enriched mixed tocopherol diet that contained 20-fold
      higher levels of gamma-tocopherol, and roughly 3-fold higher levels of alpha
      tocopherol. The effect of such diet on tumor and PIN development was observed.
      The expression of phase II detoxifying, antioxidant enzymes and Nrf2 mRNA and
      protein were determined by RT-PCR, immunohistochemistry and western blotting
      techniques. Treatment with gamma-T-enriched mixed tocopherols significantly
      suppressed the incidence of palpable tumor and Prostate Intraepithelial Neoplasia
      (PIN) development without affecting the expression of the transgene (SV-40).
      Tumor progression occurred with a significant suppression of antioxidant enzymes
      such as catalase, superoxide dismutase, glutathione peroxidase, heme-oxygenase-1
      and phase II detoxifying enzymes. Treatment with gamma-T-enriched mixed
      tocopherol diet upregulated the expression of most detoxifying and antioxidant
      enzymes. Nrf2-a redox sensitive transcription factor known to mediate the
      expression of phase II detoxifying enzymes, was also significantly upregulated
      following treatment with gamma-T-enriched mixed tocopherol diet. Gamma-T-enriched
      mixed tocopherols significantly up-regulated the expression of Nrf2 and its
      related detoxifying and antioxidant enzymes thereby suppressing PIN and tumor
      development.

PMID- 19115204
TI  - Decreased expression of angiogenesis antagonist EFEMP1 in sporadic breast cancer
      is caused by aberrant promoter methylation and points to an impact of EFEMP1 as
      molecular biomarker.
AB  - EGF-containing fibulin-like extracellular matrix protein 1 (EFEMP1) was recently
      described as an antagonist of angiogenesis. Motivated by a strong dependence of
      tumor growth and metastasis on angiogenesis, we investigated the role of EFEMP1
      in human breast cancer. We applied RNA microarray expression analysis and
      quantitative real-time PCR (QRT) in a total of 45 sporadic breast cancer tissues
      and found EFEMP1 down-regulation in 59% and 61% of the analyzed tissues,
      respectively. This down-regulation was confirmed on protein level.
      Immunohistochemistry in 211 breast cancer tissues resulted in reduced or even
      abolished EFEMP1 expression in 57-62.5% of the tumors. Bisulphite genomic
      sequencing in breast cancer cell lines and primary breast cancer tissues revealed
      promoter methylation as the major cause of this down-regulation. Furthermore,
      analysis of 203 clinically well characterized primary breast cancers displayed a
      significant correlation of reduced EFEMP1 protein expression with poor disease
      free (p = 0.037) and overall survival (p = 0.032), particularly in those node
      positive patients who received adjuvant anthracycline-based chemotherapy, but not
      in those treated by either cyclophosphamide-methotrexate-5-fluorouracil (CMF) or
      Tamoxifen. In summary, the presented data demonstrate for the first time the
      reduced EFEMP1 expression on RNA and protein level in a substantial number of
      sporadic breast carcinomas and its correlation with epigenetic alterations.
      Furthermore, these data point towards a possible predictive impact of EFEMP1
      expression in primary breast cancer.

PMID- 19115205
TI  - Combined anti-PDGFRalpha and PDGFRbeta targeting in non-small cell lung cancer.
AB  - Activation of the platelet-derived growth factor (PDGF)-receptors is critically
      involved into various stromal cell functions including recruitment of stromal
      cells and vascular endothelial growth factor (VEGF) induction in tumor and
      perivascular cells. To evaluate the effects of combined PDGFRalpha and -beta
      inhibition in a non-small cell lung cancer model, we stably transfected A549 lung
      cancer cells with the PDGF-A mutant PDGF-0. PDGF-0 has been generated by
      substituting amino acids in the binding region of PDGF-A with the corresponding
      VEGF-A region, leading to a decreased receptor-binding affinity and activation.
      Compared with control vector transfected cells, transfection with PDGF-0 had no
      impact on monolayer growth and apoptosis in vitro, but significantly impaired the
      number of colony formation in soft agar. After subcutaneous injections, all mice
      developed tumors within 5 days. While control vector transfected A549 cells were
      characterized by constant tumor growth, PDGF-0 transfected A549 revealed a
      reduced tumor mass (p < 0.001) with no further growth beyond 14 days (2 months
      observation time) and complete regressions in 7 of 13 cases. Immunohistochemical
      analyses revealed that PDGF-0 transfected tumors demonstrated decreased
      recruitment of periendothelial cells, while the tumor invasion zone was similar
      to control vector transfectants. Similarly, conditioned medium from PDGF-0
      transfected cells induced significantly less migration of smooth muscle cells and
      fibroblasts in vitro. Interestingly, in PDGF-0 transfectants, neither total
      vessel count nor VEGF expression were significantly altered. These studies
      demonstrate that combined inhibition of PDGFRalpha and -beta results in markedly
      decreased tumor growth in vivo because of impaired recruitment of periendothelial
      cells.

PMID- 19115206
TI  - Down-modulation of keratin 8 phosphorylation levels by PRL-3 contributes to
      colorectal carcinoma progression.
AB  - Phosphatase of regenerating liver-3 (PRL-3) is a member of the PRL protein
      tyrosine phosphatase family and has been proposed to promote the invasiveness and
      metastastic capability of colorectal cancers (CRCs); however, the underlying
      mechanisms and target molecules of PRL-3 protein remain unknown. On the basis of
      the biological significance of PRL-3 phosphatase activity confirmed by the
      catalytically inactive PRL-3 mutant (C104S) and a PRL-3 inhibitor in CRC-derived
      SW480 cells, we performed protein expression profiling to search for PRL-3
      mediated effector proteins. By a comparative study of phosphorylated proteins
      that differentially expressed in wild type and C104S mutant PRL-3-transfected
      SW480 cells; the cytoskeletal intermediate filament keratin 8 (KRT8) was
      identified as a physiological PRL-3-interacting protein. Indeed, treatment with
      the PRL-3 inhibitor effectively suppressed the phosphorylation of KRT8 at S73 and
      S431. Moreover, we detected the physiological interaction between PRL-3 and KRT8
      and their colocalization at cellular lamellipodias and ruffles in vivo. In CRC
      tissue samples, tumor cells with high PRL-3 expression showed reduction or loss
      of phosphorylated KRT8 expression, particularly at the invasive front and in the
      liver metastases. In conclusion, our results indicate that PRL-3 may play an
      important role for the promotion of CRC cell migration and metastatic potential
      through direct KRT8 dephosphorylation.

PMID- 19115207
TI  - A-FABP, a candidate progression marker of human transitional cell carcinoma of
      the bladder, is differentially regulated by PPAR in urothelial cancer cells.
AB  - Superficial pT1 bladder tumors are characterized by a high risk of recurrence and
      progression in grade and stage. Few studies provided evidence that loss of
      adipocyte-fatty acid binding protein (A-FABP) expression was associated with
      bladder cancer progression. A-FABP is a lipid binding protein playing a role in
      intracellular lipid transport and metabolism, as well as in signal transduction.
      We reported from bladder tumors that decrease of A-FABP transcript level
      significantly correlated to tumor stage and to histologic grade (p < 0.05).
      Namely, in poor prognosis high grade pT1 tumors there was a loss of A-FABP
      expression compared to good prognosis tumors suggesting that re-expression of A
      FABP could be a therapeutic approach in early stage bladder cancer to prevent
      disease progression. We demonstrated for the first time that this marker is
      upregulated by Peroxisome Proliferator-Activated Receptor (PPAR) alpha, beta and
      gamma in T24 cells (derived from an undifferentiated grade III carcinoma) and
      only by PPARbeta in RT4 cells (derived from a well differentiated grade I
      papillary tumor). This effect occurred through a PPAR-dependent transcriptional
      mechanism without modifying mRNA stability and interestingly required de novo
      protein synthesis. Data as a whole suggest a prognostic significance of A-FABP in
      bladder cancer outcome and the potential utility of overexpression of this
      protein by PPAR agonists open up new perspectives in the treatment of bladder
      cancer. (c) 2008 Wiley-Liss, Inc.

PMID- 19115209
TI  - Prevalence and type distribution of human papillomavirus in carcinoma and
      intraepithelial neoplasia of the vulva, vagina and anus: a meta-analysis.
AB  - This meta-analysis investigated human papillomavirus (HPV) prevalence in vulvar,
      vaginal and anal intraepithelial neoplasia (VIN, VAIN, AIN) grades 1-3 and
      carcinoma from 93 studies conducted in 4 continents and using PCR assays. Overall
      HPV prevalence was 67.8%, 85.3% and 40.4% among 90 VIN1, 1,061 VIN2/3 and 1,873
      vulvar carcinomas; 100%, 90.1% and 69.9% among 107 VAIN1, 191 VAIN2/3 and 136
      vaginal carcinomas; and 91.5%, 93.9% and 84.3% among 671 AIN1, 609 AIN2/3 and 955
      anal carcinomas, respectively. HPV16 was found more frequently (>75%) and HPV18
      less frequently (<10%) in HPV-positive vulvar, vaginal and anal carcinomas than
      in cervical carcinoma. HPV6 and 11 were common in VIN1 and AIN1, but not in
      VAIN1. HPV prevalence in vulvar carcinoma varied most by histological type (69.4%
      in warty-basaloid and 13.2% in keratinized type) and was also higher in women 60
      years or younger and in studies carried out in North America. HPV prevalence in
      anal carcinoma was higher among women (90.8%) than men (74.9%), but no difference
      by gender emerged in North America. The majority of AIN2/3 derived from studies
      of HIV-positive individuals and/or men who have sex with men. Among AIN2/3, HIV
      infection was associated with higher HPV prevalence, more multiple-type
      infections and a relative under-representation of HPV16. In conclusion,
      approximately 40% of vulvar, 60% of vaginal and 80% of anal carcinoma may be
      avoided by prophylactic vaccines against HPV16/18. This proportion would be
      similar for the corresponding high-grade lesions of the vagina and anus, but
      higher for VIN2/3 (75%) than for vulvar carcinoma.

PMID- 19115208
TI  - An intron 4 VNTR polymorphism of the endothelial nitric oxide synthase gene is
      associated with early-onset colorectal cancer.
AB  - Endothelial-derived nitric oxide, which is produced by endothelial nitric oxide
      synthase (eNOS), may play an important role in colorectal carcinogenesis.
      However, the putative contribution of common eNOS genetic polymorphisms to
      colorectal cancer risk remains unknown. We genotyped 3 polymorphisms of eNOS (T
      786C, G894T, and intron4b/a) in 727 colorectal adenocarcinoma cases and 736 age-
      and sex-matched healthy controls in Taiwan. Genotypes of the T-786C and G894T
      polymorphisms were determined by fluorescence polarization assays and the 27-bp
      variable number of tandem repeat (VNTR) polymorphism in intron 4 (intron4b/a) was
      analyzed by PCR. Logistic regression was used to calculate odds ratios (ORs) and
      95% confidence intervals (CIs). Among younger participants (< or =60 yrs), the
      intron4a variant genotype was associated with a significantly increased risk of
      colorectal cancer, compared with the intron4bb genotype (OR = 1.60, 95% CI = 1.04
      2.46). In addition, those young individuals bearing a greater number of high-risk
      genotypes (OR > 1, i.e., CT+TT for T-786C, ba+aa for intron4b/a, and GG for
      G894T) of eNOS had a higher colorectal cancer risk (p(trend) = 0.039). Compared
      with younger individuals without any putative high-risk genotypes, those with 3
      high-risk genotypes had a significantly greater cancer risk (OR = 1.89, 95% CI =
      1.04-3.43). Our results suggest that the eNOS intron4b/a polymorphism may
      contribute to early-onset colorectal cancer risk in the Taiwanese population.

PMID- 19115210
TI  - Common germline variation in mismatch repair genes and survival after a diagnosis
      of colorectal cancer.
AB  - The mismatch repair (MMR) genes are involved in the maintenance of genomic
      integrity. Recently, we showed that common variants in these genes are unlikely
      to contribute significantly to colorectal cancer risk. The aim of this study was
      to investigate the role of common variants in the mismatch repair pathway as
      prognostic markers in colorectal cancer patients. We genotyped 2,060 patients for
      68 SNPs in 7 mismatch repair genes (MLH1, MLH3, MSH2, MSH3, MSH6, PMS1 and PMS2),
      using a single nucleotide polymorphism (SNP) tagging approach. Genotypes at the
      tag SNPs and multi-SNP haplotypes were tested for association with overall
      survival (OS) and disease specific survival (DSS) using a Cox regression model.
      Eight SNPs and 10 haplotypes were significant at a nominal p < 0.05 in the
      univariate analyses. Stepwise analysis showed that haplotype effects were mainly
      due to associated SNPs carried by these haplotypes. After adjustment for sex, age
      at diagnosis and stage when using overall survival and stage only when using
      disease specific survival, prognostic values were unattenuated. The most
      significant SNP associated with disease specific survival after adjustment was
      rs863221, located in MSH3 (HR: 0.59, 95% confidence interval (CI) 0.42-0.82, p
      value: 0.001). In conclusion, we find some evidence that common variants in
      mismatch repair genes may contribute to survival of patients with colorectal
      cancer.

PMID- 19115211
TI  - Frequent concomitant epigenetic silencing of the stress-responsive tumor
      suppressor gene CADM1, and its interacting partner DAL-1 in nasal NK/T-cell
      lymphoma.
AB  - Nasal NK/T-cell lymphoma (NL) is a rare but clinically important entity of
      lymphoma. Its preferential incidence in Orientals but not Caucasians suggests
      possible genetic predisposition. 11q deletion is common in NL, indicating certain
      tumor suppressor genes (TSGs) at this locus involved in its pathogenesis. We
      investigated the expression and methylation of an 11q23.2 TSG, CADM1 (or TSLC1),
      and its partner DAL-1 (or EPB41L3) in NL. Methylation and silencing of CADM1 were
      detected in 2 NL and 4 of 8 (50%) of non-Hodgkin lymphoma (NHL) cell lines, but
      not in normal NK cells and normal PBMC. Absence of CADM1 protein was also
      detected in NL cell lines. 5-aza-2'-deoxycytidine (Aza) demethylation or genetic
      knockout of both DNMT1 and 3B genes restored CADM1 and DAL-1 expression. CADM1
      methylation was further detected in 36 of 45 (80%) of NL tumors. Concomitantly,
      DAL-1 was epigenetically inactivated in NL cell lines and virtually all the
      tumors with methylated CADM1. A significant correlation between the methylation
      of both genes was found (p < 0.0001). Homozygous deletion of CADM1 was detected
      in only 3 of 18 (17%) of tumors. The stress-response of CADM1 was abolished when
      its promoter becomes methylated. Our results demonstrate a frequent, predominant
      epigenetic silencing of CADM1 and DAL-1 in NL, which likely play a synergic role
      in NL pathogenesis.

PMID- 19115212
TI  - Coffee consumption and risk of colorectal cancer: a systematic review and meta
      analysis of prospective cohort studies.
AB  - An inverse association between coffee consumption and the risk of colorectal
      cancer has been found in several case-control studies, but such an association
      was not consistent in prospective cohort studies. We conducted a systematic meta
      analysis of prospective cohort studies on coffee consumption and colorectal
      cancer published up to June 2008. We combined relative risks (RR) for colorectal
      cancer comparing high vs. low categories of coffee consumption using random
      effects models. We identified 12 eligible cohort studies, which included 646,848
      participants and 5,403 cases for colorectal cancer. The summarized result of the
      meta-analysis comparing high- vs. low-consumption categories showed no
      significant effect of coffee consumption on colorectal cancer risk (RR = 0.91;
      95% confidence intervals [CI]: 0.81-1.02). The RR was 0.93 (95% CI: 0.71-1.22)
      when considering 4 studies conducted in the United States of America, 0.91 (95%
      CI: 0.76-1.10) for 5 studies from Europe, and 0.83 (95% CI: 0.62-1.10) for 3
      Japanese studies. No significant differences by sex and cancer-site were found,
      but there was a slight suggestion of an inverse association between coffee
      consumption and colon cancer in women (RR = 0.79; 95% CI: 0.60-1.04), especially
      Japanese women (RR = 0.62; 95% CI: 0.37-1.05). The suggestive inverse
      associations were slightly stronger in studies that controlled for smoking and
      alcohol, and in studies with shorter follow-up times. Information on coffee type,
      its serving size, or brewing method may provide a better understanding of this
      reassuring result and the real role of coffee on colorectal cancer risk.

PMID- 19115215
TI  - Re: KAI1/CD82 is a novel target of estrogen receptor-mediated gene repression and
      downregulated in primary human breast cancer (Int J Cancer 123: 2239-2246, 2008).

PMID- 19115217
TI  - Sorafenib: A glimmer of hope for unresectable hepatocellular carcinoma?

PMID- 19115216
TI  - Improve organ health by chewing up old proteins?

PMID- 19115218
TI  - A patient with no known liver disease presenting with a sentinel variceal
      hemorrhage.

PMID- 19115219
TI  - Viral dynamics of hepatitis B virus DNA in human immunodeficiency virus-1
      hepatitis B virus coinfected individuals: similar effectiveness of lamivudine,
      tenofovir, or combination therapy.
AB  - Following treatment of hepatitis B virus (HBV) infection with nucleos(t)ide
      reverse transcriptase inhibitors (NRTIs), there is a biphasic clearance of HBV,
      similar to that seen following treatment of human immunodeficiency virus-1 (HIV
      1) and hepatitis C virus. Little is known about the impact of combination NRTIs
      and HIV-1 coinfection on HBV viral kinetic parameters following the initiation of
      HBV-active highly active antiretroviral therapy (HAART). HIV-1-HBV coinfected
      patients (n = 21) were enrolled in a viral kinetics substudy of the Tenofovir in
      HIV-1-HBV Coinfection study (TICO). TICO was a randomized (1:1:1) trial of
      tenofovir disoproxil fumarate (TDF, 300 mg) versus lamivudine (LMV, 300 mg)
      versus TDF/LMV within an efavirenz based HAART regimen initiated in HIV-1-HBV
      coinfected antiretroviral naive individuals in Thailand. HBV DNA was measured
      frequently over the first 56 days. To fit the viral load data, we used a model of
      HBV kinetics that allows the estimation of treatment effectiveness, viral
      clearance and infected cell loss. We observed a biphasic decline in HBV DNA in
      almost all patients. We did not observe any significant differences in HBV viral
      dynamic parameters between the three treatments groups. Overall, median
      (interquartile range) HBV treatment effectiveness was 98% (95%-99%), median HBV
      virion half-life was 1.2 days (0.5-1.4 days), and median infected cell half-life
      was 7.9 days (6.3-11.0 days). When we compared hepatitis B e antigen (HBeAg)
      positive and HBeAg-negative individuals, we found a significantly longer infected
      cell half-life in HBeAg-positive individuals (6.2 versus 9.0 days, P = 0.02).
      CONCLUSION: HBV viral dynamic parameters are similar following anti-HBV NRTI
      monotherapy and dual combination therapy in the setting of HIV-1-HBV coinfection.
      HIV-1 coinfection has minimal effect on HBV viral dynamics, even in the setting
      of advanced HIV-1-related immunosuppression.

PMID- 19115220
TI  - Fibrogenesis in pediatric cholestatic liver disease: role of taurocholate and
      hepatocyte-derived monocyte chemotaxis protein-1 in hepatic stellate cell
      recruitment.
AB  - Cholestatic liver diseases, such as cystic fibrosis (CF) liver disease and
      biliary atresia, predominate as causes of childhood cirrhosis. Despite diverse
      etiologies, the stereotypic final pathway involves fibrogenesis where hepatic
      stellate cells (HSCs) are recruited, producing excess collagen which initiates
      biliary fibrosis. A possible molecular determinant of this recruitment, monocyte
      chemotaxis protein-1 (MCP-1), an HSC-responsive chemokine, was investigated in CF
      liver disease and biliary atresia. The bile-duct-ligated rat and in vitro
      coculture models of cholestatic liver injury were used to further explore the
      role of MCP-1 in HSC recruitment and proposed mechanism of induction via bile
      acids. In both CF liver disease and biliary atresia, elevated hepatic MCP-1
      expression predominated in scar margin hepatocytes, closely associated with
      activated HSCs, and was also expressed in cholangiocytes. Serum MCP-1 was
      elevated during early fibrogenesis. Similar observations were made in bile-duct
      ligated rat liver and serum. Hepatocytes isolated from cholestatic rats secreted
      increased MCP-1 which avidly recruited HSCs in coculture. This HSC chemotaxis was
      markedly inhibited in interventional studies using anti-MCP-1 neutralizing
      antibody. In CF liver disease, biliary MCP-1 was increased, positively
      correlating with levels of the hydrophobic bile acid, taurocholate. In
      cholestatic rats, increased MCP-1 positively correlated with taurocholate in
      serum and liver, and negatively correlated in bile. In normal human and rat
      hepatocytes, taurocholate induced MCP-1 expression. CONCLUSION: These
      observations support the hypothesis that up-regulation of hepatocyte-derived MCP
      1, induced by bile acids, results in HSC recruitment in diverse causes of
      cholestatic liver injury, and is a key early event in liver fibrogenesis in these
      conditions. Therapies aimed at neutralizing MCP-1 or bile acids may help reduce
      fibro-obliterative liver injury in childhood cholestatic diseases.

PMID- 19115221
TI  - Thyroid hormone receptor ligands induce regression of rat preneoplastic liver
      lesions causing their reversion to a differentiated phenotype.
AB  - Triiodothyronine (T3), through interaction with its intracellular thyroid hormone
      receptors (TRs), influences various physiological functions, including
      metabolism, development, and growth. We investigated the effect of T3 and the
      selective TR-beta agonist GC-1 in two models of hepatocarcinogenesis.
      Preneoplastic lesions were induced in F-344 rats via a single dose of
      diethylnitrosamine, followed by a choline-deficient (CD) diet for 10 weeks. Rat
      subgroups were then fed the CD diet or a CD diet containing either 4 mg/kg T3 or
      5 mg/kg GC-1 for another week. Rats fed a CD diet alone showed a large number
      (65/cm(2)) of preneoplastic lesions positive for the placental form of
      glutathione S-transferase (GSTP). Coadministration of T3 for the last week caused
      an almost complete disappearance of the foci (3/cm(2)). A reduction of GSTP
      positive foci was also observed in rats fed a CD + GC-1 diet (28/cm(2) versus
      75/cm(2) of rats fed a CD diet alone) in the absence of significant differences
      in labeling or apoptotic index of preneoplastic hepatocytes between the two
      groups. An antitumoral effect of GC-1 was also observed with the resistant
      hepatocyte model of hepatocarcinogenesis. Nodule regression was associated with a
      return to a fully differentiated phenotype, indicated by the loss of the fetal
      markers GSTP and gamma glutamyl transpeptidase, and reacquisition of the activity
      of glucose 6-phosphatase and adenosine triphosphatase, two enzymes expressed in
      normal hepatocytes. CONCLUSION: Our results indicate that activated TRs
      negatively influence the carcinogenic process through induction of a
      differentiation program of preneoplastic hepatocytes. The results also suggest
      that TRs could be a meaningful target in liver cancer therapy.

PMID- 19115222
TI  - Early serum HBsAg drop: a strong predictor of sustained virological response to
      pegylated interferon alfa-2a in HBeAg-negative patients.
AB  - Pegylated interferon alfa-2a (PEG-IFN) may induce sustained virological response
      (SVR) in 20% of hepatitis B e antigen (HBeAg)-negative chronic hepatitis B (CHB)
      patients. In addition, loss of hepatitis B surface antigen (HBsAg) is achieved
      with a 10% yearly rate after treatment cessation in sustained responders. The aim
      of this study was to assess on-treatment serum HBsAg kinetics to predict SVR in
      HBeAg-negative patients treated with PEG-IFN. Forty-eight consecutive patients
      were treated with PEG-IFN (180 microg/week) for 48 weeks. Serum hepatitis B virus
      (HBV) DNA (COBAS TaqMan) and HBsAg (Abbott Architect HBsAg QT assay) were
      assessed at baseline, during treatment (weeks 12, 24, and 48), and during follow
      up (weeks 72 and 96). SVR was defined as undetectable serum HBV DNA (<70
      copies/mL) 24 weeks after treatment cessation. Twenty-five percent of patients
      achieved SVR. They were not different from those who failed treatment regarding
      age, sex, ethnicity, HBV genotype, baseline serum HBV DNA and HBsAg levels, or
      liver histology. During treatment, serum HBsAg levels decreased only in patients
      who developed SVR, with mean decreases of 0.8 +/- 0.5, 1.5 +/- 0.6, and 2.1 +/-
      1.2 log(10) IU/mL at weeks 12, 24, and 48, respectively. A decrease of 0.5 and 1
      log(10) IU/mL in serum HBsAg levels at weeks 12 and 24 of therapy, respectively,
      had high predictive values of SVR (negative predictive value [NPV] 90%, positive
      predictive value [PPV] 89% for week 12; NPV 97%, PPV 92% for week 24). HBsAg loss
      was observed in three patients, all with SVR. CONCLUSION: Early serum HBsAg drop
      has high predictive values of SVR to PEG-IFN in HBeAg-negative CHB patients.
      Serum quantitative HBsAg may be a useful tool to optimize the management of PEG
      IFN therapy in these patients.

PMID- 19115224
TI  - The discovery of HNPC-A3066: a novel strobilurin acaricide.
AB  - BACKGROUND: Although more than ten strobilurin analogues have been commercialized
      since 1996 as fungicides, only one was available as an acaricide as of 2003. To
      search for novel strobilurin analogues with unique biological activities, a
      synthetic screening programme was carried out. RESULTS: Syntheses of compounds
      analogous to the commercialized fungicide metominostrobin and the acaricide
      fluacrypyrim led to the discovery of a lead compound, (E)-2-[2-[[3,5
      bis(trifluoromethyl)phenoxy]methyl]phenyl]-2-(methoxyimino)-N-methylacetamide
      (3b), that showed moderate acaricidal activity against Tetranychus urticae Koch.
      Compound 3b has a 3,5-(CF(3))(2)-phenoxymethyl group instead of the unsubstituted
      phenoxy substituent in metominostrobin. Optimization of compound 3b was achieved
      by introducing an oxime ether bridge along with an alkylthio(alkyl) branch in
      place of the oxymethylene chain between two aromatic moieties, as well as by
      replacing the methoxyiminoacetamide group with a methoxyacrylate structure,
      leading to (E)- methyl 2-[2-[[[(Z)[1-(3,5-bis(trifluoromethyl)phenyl)-2
      methylthioethylidene]amino]oxy] methyl]phenyl]-3-methoxyacrylate (6c) and (E)-
      methyl 2-[2-[[[(Z)[1-(3,5-bis(trifluoromethyl)phenyl)-1
      methylthiomethylidene]amino]oxy]methyl]phenyl]-3-methoxyacrylate (9a, HNPC
      A3066). CONCLUSION: The above two compounds (6c, 9a) were shown to exhibit potent
      acaricidal and fungicidal activity. Compound 9a (HNPC-A3066) also exhibits
      larvicidal and ovicidal activities against various acarids. The acaricidal
      potency is comparable with those of commercial acaricides such as fluacrypyrim,
      tebufenpyrad and chlorfenapyr.

PMID- 19115225
TI  - The problem of predicting neurological outcome in early-onset intrauterine growth
      restriction.

PMID- 19115227
TI  - Fetal Facebook: historical representations of the fetus between art and science.

PMID- 19115228
TI  - Reduced egg viability in codling moth Cydia pomonella (L.) (Lepidoptera:
      Tortricidae) following adult exposure to novaluron.
AB  - BACKGROUND: The codling moth, Cydia pomonella (L.), is one of the principal pests
      of pome fruits in the world. The effects of novaluron, a benzoylurea chitin
      synthesis inhibitor insecticide registered for use on apples in the USA, on
      fecundity and egg viability in codling moth were studied under laboratory
      conditions. Three different exposure methods were investigated: ingestion,
      contact and topical spray. Additionally, the duration of novaluron sublethal
      effects was measured subsequent to the three modes of exposure. RESULTS: The
      fecundity of codling moth adults was not significantly affected by novaluron with
      any of the exposure methods. However, novaluron did cause significant reductions
      in the proportion of egg hatch with all three exposure methods. The duration of
      sublethal effects was 9 days or more for all modes of exposure, but with the
      topical spray these effects began to diminish after 6 days. CONCLUSION: Novaluron
      does not affect fecundity in codling moth, but has significant sublethal activity
      by reducing egg viability subsequent to adult exposure. The topical, contact and
      ingestion exposures all induce sublethal effects after exposure, and these
      persist to various degrees throughout codling moth oviposition. A more complete
      understanding of novaluron's lethal and sublethal activities will help IPM
      practitioners optimize its use for management of the codling moth.

PMID- 19115229
TI  - First-trimester screening markers are altered in pregnancies conceived after
      IVF/ICSI.
AB  - OBJECTIVES: To determine the levels of first-trimester screening markers and to
      assess the false-positive rate for first-trimester combined screening for Down
      syndrome in a large national population of women pregnant after assisted
      reproductive technology (ART), in order to decide whether or not to correct risk
      calculation for mode of conception. METHODS: A national prospective cohort study
      of 1000 pregnancies achieved after ART was compared with a control group of 2543
      pregnancies conceived spontaneously. All women completed a first-trimester
      combined screening program. Risk calculation was performed retrospectively based
      on the screening parameters to avoid bias due to the use of different algorithms
      of risk calculation. RESULTS: In chromosomally normal pregnancies conceived after
      in-vitro fertilization (IVF) and intracytoplasmic sperm injection (ICSI), the
      pregnancy-associated plasma protein-A multiples of the median value was
      significantly decreased when compared with that of pregnancies conceived
      spontaneously (0.78 and 0.79 vs. 0.98), while there was no difference in the
      group treated by frozen embryo replacement. There was no difference in the level
      of free beta-human chorionic gonadotropin between groups. The median nuchal
      translucency thickness was smaller in the overall ART group compared with
      controls. The false-positive rate of first-trimester combined screening in the
      overall ART group, adjusted for maternal age, was significantly higher when
      compared with controls (9.0% vs. 6.0%). CONCLUSIONS: It seems advisable to use a
      population of IVF/ICSI pregnancies to establish median curves for the first
      trimester serum screening parameters and perhaps also for nuchal translucency
      thickness. However, care must be taken, as different ART treatment methods and
      aspects of medical history seem to alter the screening parameters in different
      ways.

PMID- 19115230
TI  - Second-trimester fetal growth as a predictor of poor obstetric and neonatal
      outcome in patients with low first-trimester serum pregnancy-associated plasma
      protein-A and a euploid fetus.
AB  - OBJECTIVE: To examine if fetal growth during the second trimester predicts poor
      pregnancy and neonatal outcome in patients with low first-trimester serum
      pregnancy-associated plasma protein-A (PAPP-A) and a euploid fetus. METHODS: We
      identified all patients with first-trimester PAPP-A<5th centile who had undergone
      first- and second-trimester ultrasound examination. We excluded multiple
      pregnancies and those with aneuploidy or major anomalies identified before or
      after birth. We compared pregnancies with and without ultrasound markers for
      fetal growth restriction at 18-24 weeks. RESULTS: We identified 239 patients with
      low PAPP-A, 25 (10.5%) of whom had evidence of fetal growth restriction at 18-24
      weeks. These 25 cases had significantly higher rates of third-trimester small-for
      gestational age (SGA) fetus, gestational hypertension, preterm birth, indicated
      preterm birth, low birth weight and birth weight centiles, 1-min Apgar score<7,
      neonatal intensive care unit admission and fetal or neonatal death. CONCLUSION:
      Among patients with low first-trimester PAPP-A and a euploid fetus, fetal growth
      in the second trimester can predict poor obstetric and neonatal outcome.

PMID- 19115231
TI  - Monitoring of fetuses with intrauterine growth restriction: longitudinal changes
      in ductus venosus and aortic isthmus flow.
AB  - OBJECTIVES: To explore in growth-restricted fetuses the sequence of changes in
      aortic isthmus and ductus venosus blood flow in relation to other arterial
      Doppler parameters commonly used to evaluate fetal wellbeing. METHODS: Umbilical
      and middle cerebral arteries, ductus venosus and aortic isthmus were explored
      serially by means of pulsed Doppler in a cohort of singleton small-for
      gestational age fetuses requiring delivery before 34 weeks. Longitudinal changes
      in the last 30 days before delivery were modeled by multilevel analysis.
      Individual regression lines for each variable were calculated for each fetus and
      from these the regression lines for the whole group were derived, in order to
      estimate the mean time point at which each Doppler parameter became abnormal
      (outside the 5th-95th centile range). A survival analysis was performed during
      the monitoring period, in which the endpoint was an abnormal Doppler pulsatility
      index. RESULTS: A total of 162 observations were performed on 46 fetuses (median,
      3; range, 2-10). The median gestational age at inclusion was 28.9 (range, 23.6
      33.4) weeks and delivery occurred at a median gestational age of 30.5 (range,
      25.9-33.9) weeks. Six (13%) cases of perinatal mortality occurred. Umbilical and
      middle cerebral artery Doppler showed an almost linear deterioration throughout
      monitoring, becoming abnormal on average 24 days and 20 days before delivery,
      respectively. Aortic isthmus Doppler became abnormal on average 13 days before
      delivery, while ductus venosus Doppler did so within the last week before
      delivery. CONCLUSIONS: In preterm growth-restricted fetuses, aortic isthmus blood
      flow becomes abnormal on average 1 week earlier than does that in the ductus
      venosus. This could provide a sound basis to better define management protocols
      aimed to improve intact fetal survival.

PMID- 19115232
TI  - Current status of insecticide resistance in Q biotype Bemisia tabaci populations
      from Crete.
AB  - BACKGROUND: A major problem of crop protection in Crete, Greece, is the control
      of Bemisia tabaci (Gennadius) (Homoptera: Aleyrodidae) with chemical insecticides
      owing to the rapid development of resistance. The aim of this study was to
      investigate the establishment of resistance and the underlying mechanisms to
      major insecticide classes with classical bioassays and known biochemical
      resistance markers. RESULTS: During a 2005-2007 survey, 53 Q biotype populations
      were collected. Application history records showed extensive use of
      neonicotinoids, organophosphates, carbamates and pyrethroids. High resistance
      levels were identified in the majority of populations (>80%) for imidacloprid
      (RF: 38-1958x) and alpha-cypermethrin (RF: 30-600x). Low resistance levels (RF <
      12) were observed for pirimiphos-methyl. A strong correlation between resistance
      to imidacloprid and the number of applications with neonicotinoids was observed.
      Significant correlations were observed between COE and P450-dependent
      monoxygenase activity with resistance to alpha-cypermethrin and imidacloprid
      respectively. A propoxur-based AChE diagnostic test indicated that iAChE was
      widespread in most populations. Resistance levels for alpha-cypermethrin were
      increased when compared with a previous survey (2002-2003). Differentiation of
      LC(50) values between localities was observed for imidacloprid only. CONCLUSION:
      Bemisia tabaci resistance evolved differently in each of the three insecticides
      studied. Imidacloprid resistance seems less established and less persistent than
      alpha-cypermethrin resistance. The low resistance levels for pirimiphos-methyl
      suggest absence of cross-resistance with other organophosphates or carbamates
      used.

PMID- 19115233
TI  - Loss of profilin-1 expression enhances breast cancer cell motility by Ena/VASP
      proteins.
AB  - We previously showed that silencing profilin-1 (Pfn1) expression increases breast
      cancer cell motility, but the underlying mechanisms have not been explored.
      Herein, we demonstrate that loss of Pfn1 expression leads to slower but more
      stable lamellipodial protrusion thereby enhancing the net protrusion rate and the
      overall motility of MDA-MB-231 breast cancer cells. Interestingly, MDA-MB-231
      cells showed dramatic enrichment of VASP at their leading edge when Pfn1
      expression was downregulated and this observation was also reproducible in other
      cell types including human mammary epithelial cells and vascular endothelial
      cells. We further demonstrate that Pfn1 downregulation results in a hyper-motile
      phenotype of MDA-MB-231 cells in an Ena/VASP-dependent mechanism. Pfn1-depleted
      cells display a strong colocalization of VASP with lamellipodin (Lpd--a
      PI(3,4)P(2)-binding protein that has been previously implicated in lamellipodial
      targeting of Ena/VASP) at the leading edge. Finally, inhibition of PI3-kinase
      (important for generation of PI(3,4)P(2)) delocalizes VASP from the leading edge.
      This observation is consistent with a possible involvement of Lpd in enhanced
      membrane recruitment of VASP that results from loss of Pfn1 expression. Our
      findings for the first time highlight a possible mechanism of how reduced
      expression of a pro-migratory molecule like Pfn1 could actually promote motility
      of breast cancer cells.

PMID- 19115234
TI  - Fifty hertz extremely low-frequency magnetic field exposure elicits redox and
      trophic response in rat-cortical neurons.
AB  - Large research activity has raised around the mechanisms of interaction between
      extremely low-frequency magnetic fields (ELF-MFs) and biological systems. ELF-MFs
      may interfere with chemical reactions involving reactive oxygen species (ROS),
      thus facilitating oxidative damages in living cells. Cortical neurons are
      particularly susceptible to oxidative stressors and are also highly dependent on
      the specific factors and proteins governing neuronal development, activity and
      survival. The aim of the present work was to investigate the effects of exposures
      to two different 50 Hz sinusoidal ELF-MFs intensities (0.1 and 1 mT) in maturing
      rat cortical neurons' major anti-oxidative enzymatic and non-enzymatic cellular
      protection systems, membrane peroxidative damage, as well as growth factor, and
      cytokine expression pattern. Briefly, our results showed that ELF-MFs affected
      positively the cell viability and concomitantly reduced the levels of apoptotic
      death in rat neuronal primary cultures, with no significant effects on the main
      anti-oxidative defences. Interestingly, linear regression analysis suggested a
      positive correlation between reduced glutathione (GSH) and ROS levels in 1 mT MF
      exposed cells. On this basis, our hypothesis is that GSH could play an important
      role in the antioxidant defence towards the ELF-MF-induced redox challenge.
      Moreover, the GSH-based cellular response was achieved together with a brain
      derived neurotrophic factor over-expression as well as with the interleukin 1beta
      dependent regulation of pro-survival signaling pathways after ELF-MF exposure.

PMID- 19115235
TI  - Genome based cell population heterogeneity promotes tumorigenicity: the
      evolutionary mechanism of cancer.
AB  - Cancer progression represents an evolutionary process where overall genome level
      changes reflect system instability and serve as a driving force for evolving new
      systems. To illustrate this principle it must be demonstrated that karyotypic
      heterogeneity (population diversity) directly contributes to tumorigenicity. Five
      well characterized in vitro tumor progression models representing various types
      of cancers were selected for such an analysis. The tumorigenicity of each model
      has been linked to different molecular pathways, and there is no common molecular
      mechanism shared among them. According to our hypothesis that genome level
      heterogeneity is a key to cancer evolution, we expect to reveal that the common
      link of tumorigenicity between these diverse models is elevated genome diversity.
      Spectral karyotyping (SKY) was used to compare the degree of karyotypic
      heterogeneity displayed in various sublines of these five models. The cell
      population diversity was determined by scoring type and frequencies of clonal and
      non-clonal chromosome aberrations (CCAs and NCCAs). The tumorigenicity of these
      models has been separately analyzed. As expected, the highest level of NCCAs was
      detected coupled with the strongest tumorigenicity among all models analyzed. The
      karyotypic heterogeneity of both benign hyperplastic lesions and premalignant
      dysplastic tissues were further analyzed to support this conclusion. This common
      link between elevated NCCAs and increased tumorigenicity suggests an evolutionary
      causative relationship between system instability, population diversity, and
      cancer evolution. This study reconciles the difference between evolutionary and
      molecular mechanisms of cancer and suggests that NCCAs can serve as a biomarker
      to monitor the probability of cancer progression.

PMID- 19115237
TI  - Ultrasound factors to predict the outcome of external cephalic version: a meta
      analysis.
AB  - OBJECTIVE: To systematically review the medical literature reporting on
      ultrasound factors that can be predictive for the outcome of an attempt at
      external cephalic version (ECV). METHODS: MEDLINE, EMBASE and Cochrane Central
      Register of Controlled Trials were searched. Studies reporting on potential
      ultrasound prognosticators and ECV success rates that allowed construction of a
      2x2 table were selected. RESULTS: We selected 37 primary articles reporting on
      7709 women. Posterior placental location (odds ratio (OR), 1.9; 95% CI, 1.5-2.4),
      complete breech position (OR, 2.3; 95% CI, 1.9-2.8) and an amniotic fluid
      index>10 (OR, 1.8; 95% CI, 1.5-2.1) were predictors of successful ECV.
      CONCLUSION: Success of an ECV attempt is associated with ultrasound parameters
      such as fetal position, amniotic fluid and placental location. This knowledge can
      be used to develop a prognostic model to predict successful ECV.

PMID- 19115236
TI  - Prevalence of endometrial polyps and abnormal uterine bleeding in a Danish
      population aged 20-74 years.
AB  - OBJECTIVE: To estimate the prevalence of endometrial polyps and to investigate
      associated abnormal uterine bleeding in a Danish population aged 20-74 years.
      METHODS: This was a study of a random selection of women from the Danish Civil
      Registration System: 1660 women were invited of whom 686 were included (429 pre-
      and 257 postmenopausal). AUB was assessed by a validated questionnaire. The women
      underwent transvaginal sonography (TVS) and saline contrast sonohysterography
      (SCSH). Hysteroscopic resection was performed in cases with suspected focal
      intrauterine pathology. Full evaluation was performed in 619 women (two failures
      of TVS and 60 failures of SCSH, in two women SCSH was contraindicated
      (endometrial cancer), in two women hysteroscopy was contraindicated, and one
      polyp was lost before histology). World Health Organization histopathological
      criteria were used for diagnosing true endometrial polyps. RESULTS: On final
      diagnosis there were 48 women with polyps, eight with submucosal myomas, four
      with other benign findings and one with polypoidal growing endometrial cancer.
      Complex hyperplasia without atypia was diagnosed in two women with polyps. The
      prevalence of endometrial polyps was 7.8% (48/619; 95% CI, 5.6-9.9%). The
      prevalence was influenced significantly by age (P<0.005); in women below the age
      of 30 years, the prevalence was 0.9%. Polyps were diagnosed in 5.8% of pre- and
      11.8% of postmenopausal women (P<0.01). Thirty-nine (82%) of the women who had
      histopathologically verified polyps were asymptomatic. In asymptomatic
      premenopausal women the prevalence of polyps was 7.6%, while it was 13% in
      asymptomatic postmenopausal women. AUB, in particular intermenstrual bleeding,
      was more frequent among women without polyps (38%). By ultrasound examination,
      submucosal myomas were diagnosed in 4.2% (26/622; 95% CI, 2.6-5.8%) and
      intramural myomas in 11.1% (76/684; 95% CI, 8.8-13.5%) of women. Polyps were
      diagnosed in 2% of oral-contraceptive and 25% of hormone-therapy users.
      CONCLUSIONS: The overall prevalence of endometrial polyps was 7.8% and the
      prevalence increased with age. Polyps were rare (0.9%) in women below the age of
      30 years. Surprisingly, AUB was less frequent among women with polyps than among
      those without polyps.

PMID- 19115240
TI  - A computerized system for signal detection in spontaneous reporting system of
      Shanghai China.
AB  - PURPOSE: We developed a computerized system for signal detection in spontaneous
      reporting system (SRS) of Shanghai. Data acquisition, data mining could be
      carried out automatically and the process of data preprocessing and cleaning
      could be facilitated. This system was expected to detect signals from SRS after
      drug licensing with minimum patient exposure. METHODS: This system was developed
      by Microsoft visual basic (VB) 6.0. Data preprocessing, data cleaning, and data
      mining were based upon visual basic for application (VBA) in Microsoft Excel
      2003. Database of drug generic name and adverse drug reaction (ADR) standard
      dictionary were set up initially for data cleaning and coding. Algorithms
      including reporting odds ratio (ROR), proportional reporting ratio (PRR), measure
      used by the Medicines and Healthcare Products Regulatory Agency (MHRA), Bayesian
      confidence propagation neural network (BCPNN) were employed in this system. Crude
      ADR reports submitted to Shanghai ADR SRS from December 2003 to April 2007 were
      used as a material in this study to test the feasibility and flexibility of this
      system. RESULTS: Thirty two thousand seven hundred and fourty six crude ADR
      reports were acquired from the SRS automatically. Two thousand one hundred and
      fourty seven drug generic name and 621 ADR name were kept in the database after
      data preprocessing and cleaning. A total of 1430, 1419, 868 and 997 possible drug
      ADR signals were generated by ROR, PRR, BCPNN and MHRA, respectively.
      CONCLUSIONS: The results indicate that this computerized system is a flexible one
      that can help to detect possible drug-ADR signals intelligently in SRS of
      Shanghai now. It is a promising system for post-marketing surveillance on both
      chemical medicine and Chinese traditional medicine.

PMID- 19115241
TI  - Influence of glyphosate, crop volunteer and root pathogens on glyphosate
      resistant wheat under controlled environmental conditions.
AB  - BACKGROUND: The herbicide glyphosate has a synergistic effect on root disease
      because of increased susceptibility from reduced plant defenses resulting from
      the blockage of the shikimic acid pathway. Could glyphosate-resistant (GR) wheat
      cultivars and glyphosate application in-crop increase the risk of damage from
      soil-borne pathogens? Growth chamber experiments were conducted with two GR wheat
      lines and their corresponding glyphosate-sensitive (GS) parents and four
      pathogens (Rhizoctonia solani Kuhn R. oryzae Ryker & Gooch, Gaeumannomyces
      graminis (Sacc.) v. Arx & J. Olivier var. tritici J. Walker and Pythium ultimum
      Trow). Treatments consisted of different herbicide timings and planting of crop
      volunteer to mimic management practices in the field. RESULTS: GR cultivars were
      not inherently more susceptible to root pathogens than GS cultivars, and
      application of glyphosate did not increase root disease. When crop volunteer was
      grown in close proximity to GR cultivars, the timing of glyphosate application
      had a profound effect. In general, the longer the crop volunteer was left before
      killing with glyphosate, the greater was the competitive effect on the planted
      crop. Both R. solani and G. graminis var. tritici reduced plant height, number of
      tillers and root length of the GR cultivars in the presence of crop volunteer
      with glyphosate application. CONCLUSION: To minimize the damaging effects of
      these pathogens, producers should apply glyphosate at least 2-3 weeks before
      planting GR wheat, as currently advised for GS cereals.

PMID- 19115242
TI  - Strigolactones: ecological significance and use as a target for parasitic plant
      control.
AB  - Parasitic weeds cause severe damage to important agricultural crops. Although
      some promising control methods against these parasitic plants have been
      developed, new strategies continue to be relevant in integrated approaches. The
      life cycle for root parasitic weeds is intimately associated with their host and
      is a suitable target for such new control strategies, particularly when directed
      at the early stages of the host-parasite interaction. Here, the authors focus on
      knowledge of the germination stimulants-strigolactones-for the root parasitic
      plants Striga and Orobanche spp. and discuss their biosynthetic origin,
      ecological significance and physiological and biochemical regulation. In
      addition, the existing and possible new control strategies that are based on this
      knowledge, and that could lead to more efficient control methods against these
      root parasitic weeds, are reviewed.

PMID- 19115243
TI  - Characterisation and developmental potential of ovine bone marrow derived
      mesenchymal stem cells.
AB  - Since discovery, significant interest has been generated in the potential
      application of mesenchymal stem cells or multipotential stromal cells (MSC) for
      tissue regeneration and repair, due to their proliferative and multipotential
      capabilities. Although the sheep is often used as a large animal model for
      translating potential therapies for musculoskeletal injury and repair, the
      characteristics of MSC from ovine bone marrow have been inadequately described.
      Histological and gene expression studies have previously shown that ovine MSC
      share similar properties with human and rodents MSC, including their capacity for
      clonogenic growth and multiple stromal lineage differentiation. In the present
      study, ovine bone marrow derived MSCs positively express cell surface markers
      associated with MSC such as CD29, CD44 and CD166, and lacked expression of CD14,
      CD31 and CD45. Under serum-deprived conditions, proliferation of MSC occurred in
      response to EGF, PDGF, FGF-2, IGF-1 and most significantly TGF-alpha. While
      subcutaneous transplantation of ovine MSC in association with a ceramic HA/TCP
      carrier into immunocomprimised mice resulted in ectopic osteogenesis,
      adipogenesis and haematopoietic-support activity, transplantation of these cells
      within a gelatin sponge displayed partial chondrogenesis. The comprehensive
      characterisation of ovine MSC described herein provides important information for
      future translational studies involving ovine MSC.

PMID- 19115244
TI  - The relative potency and safety of endothelial progenitor cells and unselected
      mononuclear cells for recovery from myocardial infarction and ischemia.
AB  - Endothelial progenitor cells (EPCs) are a subset of the total mononuclear cell
      population (tMNCs) that possess an enhanced potential for differentiation within
      the endothelial-cell lineage. Typically, EPCs are selected from tMNCs via the
      expression of both hematopoietic stem-cell markers and endothelial-cell markers,
      such as CD34, or by culturing tMNCs in media selective for endothelial cells.
      Both EPCs and tMNCs participate in vascular growth and regeneration, and their
      potential use for treatment of myocardial injury or disease has been evaluated in
      early-phase clinical studies. Direct comparisons between EPCs and tMNCs are rare,
      but the available evidence appears to favor EPCs, particularly CD34+ cells, and
      the potency of EPCs may be increased as much as 30-fold through genetic
      modification. However, these observations must be interpreted with caution
      because clinical investigations of EPC therapy are ongoing. We anticipate that
      with continued development, EPC therapy will become a safe and effective
      treatment option for patients with acute myocardial infarction or chronic
      ischemic disease.

PMID- 19115245
TI  - Long-term results of quality of life after standard laparoscopic vs. robot
      assisted laparoscopic fundoplications for gastro-oesophageal reflux disease. A
      comparative clinical trial.
AB  - BACKGROUND: The role of telematic surgical approach in gastro-oesophageal reflux
      disease (GERD) is still unclear. METHODS: The aim of the study is to assess
      disease specific symptoms and quality of life in patients with GERD treated with
      either traditional laparoscopic (TL) or robot-assisted fundoplication using the
      Da Vinci system (DV) in long-term follow-up. RESULTS: Eighty patients underwent a
      fundoplication in 2003. Four years later all patients were given a standardized
      questionnaire and 59 (74%) replied. The TL group included 44 patients (18 male/26
      female) and the DV group 15 patients (9 male/6 female); the mean operating time
      was 116 min for the TL group and 207 min for the DV group (p < 0.001). The mean
      GIQLI score was 106 points for TL and 107 points in the DV (p > 0.05).
      CONCLUSIONS: Although a safe and feasible procedure, high functional costs of the
      Da Vinci system and longer operating time prevent this operation from being the
      standard surgical procedure for GERD.

PMID- 19115246
TI  - Computer-assisted surgery for dynamic hip screw, using Surgix, a novel
      intraoperative guiding system.
AB  - BACKGROUND: We present Surgix, a new computer-assisted surgery system (CASS).
      This system uses image analysis technology in order to measure three-dimensional
      (3D) distances, visualize implant templates and view the guided trajectory on
      standard fluoroscopy. Our purpose was to compare surgery results and technique
      with and without the Surgix CASS. METHODS: The study included 61 dynamic hip
      screw (DHS) procedures. The Surgix system was used in 41 procedures. We compared
      the number of guide wire insertion trials and the time needed for each trial, the
      number of X-ray pulses, tip-apex index, nine-quadrant position and shaft-neck
      angle. RESULTS: The procedures were carried out by experienced users (> or = five
      operations, using the system) and had a first-trial guide wire insertion success
      rate of 77.8%, compared to a rate of 10% for the control group (p = 0.001) and
      fewer insertion trials (1.33 vs. 3.05, respectively; p = 0.001). The mean number
      of fluoroscopy pulses was 41.5% lower for the experienced group than for the
      control (17.6 vs. 30.1; p = 0.009). There were no significant differences in tip
      apex distance, favourable quadrant screw placement or neck-shaft angle.
      CONCLUSION: The results of this study demonstrate that the Surgix CASS
      significantly improves the accuracy of hardware positioning and reduces radiation
      exposure time, thus enhancing patient outcome.

PMID- 19115247
TI  - HDAC4 contributes to IL-1-induced mPGES-1 expression in human synovial
      fibroblasts through up-regulation of Egr-1 transcriptional activity.
AB  - Microsomal prostaglandin E synthase-1 (mPGES-1) catalyzes the terminal step in
      the biosynthesis of PGE(2), which contributes to many physiopathological
      processes. We show here that inhibitors of histone deacetylase (HDAC) activity,
      trichostatin A (TSA), butyric acid (BA), and valproic acid (BA) prevented IL-1
      induced mPGES-1 protein expression in human synovial fibroblasts. TSA also
      inhibited IL-1-induced mPGES-1 mRNA expression and promoter activation.
      Overexpression of HDAC4, but not of HDAC1, 2, 3, 5, or 6 enhanced, whereas HDAC4
      silencing with small interfering RNA (siRNA) reduced, IL-1-induced mPGES-1
      promoter activation, implying that HDAC4 contributes to mPGES-1 gene expression.
      Consistently, IL-1-induced mPGES-1 protein expression was prevented by siRNA for
      HDAC4. We also demonstrate that IL-1-induced HDAC4 recruitment to the mPGES-1
      promoter. This recruitment was not accompanied by deacetylation of histones H3
      and H4, suggesting that HDAC4 contributes to mPGES-1 induction independently of
      local deacetylation of histones H3 and H4. We then investigated whether HDAC4
      regulates mPGES-1 expression by modulating the activity of Egr-1, a key
      transcription factor in IL-1-induced mPGES-1 expression. We found that HDAC4
      overexpression enhances, whereas HDAC4 knockdown by siRNA reduces Egr-1-mediated
      activation of the mPGES-1 promoter. Together these data indicate that HDAC4
      contributes to transcriptional induction of mPGES-1 by IL-1 through a mechanism
      involving up-regulation of Egr-1 transcriptional activity.

PMID- 19115248
TI  - Effect of tamoxifen and retinoic acid on bradykinin induced proliferation in MCF
      7 cells.
AB  - Chemopreventive approaches for the treatment of breast cancer have been validated
      clinically and with in vitro studies. The combined action of tamoxifen/all-trans
      retinoic acid was advantageous in MCF-7 cells, reducing cell proliferation, Bcl-2
      and c-Myc protein levels and increasing E-Cadherin protein levels and Gap
      junctional Intercellular Communication. We further investigated their combined
      effect in the presence of bradykinin, a pro-inflammatory agent, previously
      reported to contribute to the proliferation of breast cancer cells. Bradykinin
      increased MCF-7 cell proliferation, c-Myc levels and ERK1/2 activity. The co
      incubation of bradykinin-MCF-7 cells with tamoxifen/all-trans retinoic acid
      reduced cell proliferation, ERK1/2 activity, as well as Bcl-2, c-Myc, and
      bradykinin receptor-2 levels, without altering the enhanced E-cadherin levels
      induced by tamoxifen/all-trans retinoic acid. We showed that the anti-tumoral
      effect of tamoxifen/all-trans retinoic acid is beneficial in MCF-7 breast cancer
      cells grown in a bradykinin-pro-mitogenic environment, an effect that might be,
      at least in part, through the MAPK pathway and B2-bradykinin receptor inhibition.

PMID- 19115249
TI  - 8-Chloro-adenosine-induced E2F1 promotes p14ARF gene activation in H1299 cells
      through displacing Sp1 from multiple overlapping E2F1/Sp1 sites.
AB  - The regulation of p14ARF gene by E2F transcription factor, which differs from
      that of classical E2F targets, has recently been attributed to a variant E2F
      response element. However, promoter assays suggest multiple elements present in
      the p14ARF promoter and argue against the idea that the ARF promoter has a unique
      ability to distinguish between aberrant and physiological levels of E2F1.
      Therefore, the functional characterization of the promoter still needs to be
      done. We demonstrate that at least two overlapping E2F1/Sp1 binding sites are
      present in the p14ARF promoter, and E2F1 activates the promoter through
      displacing constitutive Sp1 from the overlapping sites. We found that 8-chloro
      adenosine (a metabolite of 8-Cl-cAMP) exposure induced the p14ARF gene in human
      lung cancer H1299 cells, followed by increased expression of E2F1 and
      constitutive expression of Sp1. The combination of cotransfection and
      electrophoretic mobility shift assay (EMSA) indicated that constitutive binding
      of Sp1 to the overlapping sites contributed to a constitutive expression of the
      ARF gene in unexposed H1299, whereas displacing Sp1 from the overlapping sites by
      E2F1 promoted the gene activation after exposure. EMSA and chromatin
      immunoprecipitation revealed increased association of E2F1 with the overlapping
      sites in the active promoter in 8-Cl-Ado-exposed cells. Together, these data
      suggest that the overlapping E2F1/Sp1 site, being present in multiple copies in
      the p14ARF promoter, may serve as the targets for both E2F1 and Sp1, thereby
      playing a crucial role in response to some oncogenic signals and stimulators,
      which activate the ARF gene through inducing E2F in the cell.

PMID- 19115250
TI  - T-box 3 negatively regulates osteoblast differentiation by inhibiting expression
      of osterix and runx2.
AB  - T-box (Tbx)3, a known transcriptional repressor, is a member of a family of
      transcription factors, which contain a highly homologous DNA binding domain known
      as the Tbx domain. Based on the knowledge that mutation of the Tbx3 gene results
      in limb malformation, Tbx3 regulates osteoblast proliferation and its expression
      increases during osteoblast differentiation, we predicted that Tbx3 is an
      important regulator of osteoblast cell functions. In this study, we evaluated the
      consequence of transgenic overexpression of Tbx3 on osteoblast differentiation.
      Retroviral overexpression increased Tbx3 expression >100-fold at the mRNA and
      protein level. Overexpression of Tbx3 blocked mineralized nodule formation (28 +/
      8 vs. 7 +/- 1%) in MC3T3-E1 cells. In support of these data, alkaline
      phosphatase (ALP) activity was reduced 33-70% (P < 0.05) in both MC3T3-E1 cells
      and primary calvaria osteoblasts overexpressing Tbx3. In contrast, Tbx3
      overexpression did not alter ALP activity in bone marrow stromal cells. Tbx3
      overexpression blocked the increase in expression of key osteoblast marker genes,
      ALP, bone sialoprotein, and osteocalcin that occurs during normal osteoblast
      differentiation, but had little or no effect on expression of proliferation genes
      p53 and Myc. In addition, Tbx3 overexpression abolished increased osterix and
      runx2 expression observed during normal osteoblast differentiation, but the
      change in Msx1 and Msx2 expression over time was similar between control and Tbx3
      overexpressing cells. Interestingly, osterix and runx2, but not Msx1 and Msx2,
      contain Tbx binding site in the regulatory region. Based on these data and our
      previous findings, we conclude that Tbx3 promotes proliferation and suppresses
      differentiation of osteoblasts and may be involved in regulating expression of
      key transcription factors involved in osteoblast differentiation.

PMID- 19115251
TI  - Autophosphorylation of carboxy-terminal residues inhibits the activity of protein
      kinase CK1alpha.
AB  - CK1 constitutes a protein kinase subfamily that is involved in many important
      physiological processes. However, there is limited knowledge about mechanisms
      that regulate their activity. Isoforms CK1delta and CK1epsilon were previously
      shown to autophosphorylate carboxy-terminal sites, a process which effectively
      inhibits their catalytic activity. Mass spectrometry of CK1alpha and splice
      variant CK1alphaL has identified the autophosphorylation of the last four
      carboxyl-end serines and threonines and also for CK1alphaS, the same four
      residues plus threonine-327 and serine-332 of the S insert. Autophosphorylation
      occurs while the recombinant proteins are expressed in Escherichia coli. Mutation
      of four carboxy-terminal phosphorylation sites of CK1alpha to alanine
      demonstrates that these residues are the principal but not unique sites of
      autophosphorylation. Treatment of autophosphorylated CK1alpha and CK1alphaS with
      lambda phosphatase causes an activation of 80-100% and 300%, respectively.
      Similar treatment fails to stimulate the CK1alpha mutants lacking
      autophosphorylation sites. Incubation of dephosphorylated enzymes with ATP to
      allow renewed autophosphorylation causes significant inhibition of CK1alpha and
      CK1alphaS. The substrate for these studies was a synthetic canonical peptide for
      CK1 (RRKDLHDDEEDEAMS*ITA). The stimulation of activity seen upon
      dephosphorylation of CK1alpha and CK1alphaS was also observed using the known CK1
      protein substrates DARPP-32, beta-catenin, and CK2beta, which have different CK1
      recognition sequences. Autophosphorylation effects on CK1alpha activity are not
      due to changes in Km(app) for ATP or for peptide substrate but rather to the
      catalytic efficiency per pmol of enzyme. This work demonstrates that CK1alpha and
      its splice variants can be regulated by their autophosphorylation status.

PMID- 19115252
TI  - The truncated Hoxa1 protein interacts with Hoxa1 and Pbx1 in stem cells.
AB  - Hox genes contain a homeobox encoding a 60-amino acid DNA binding sequence. The
      Hoxa1 gene (Hox1.6, ERA1) encodes two alternatively spliced mRNAs that encode
      distinct proteins, one with the homeodomain (Hoxa1-993), and another protein
      lacking this domain (Hoxa1-399). The functions of Hoxa1-399 are unknown. We
      detected Hoxa1-993 and Hoxa1-399 by immunoprecipitation using Hoxa1 antibodies.
      To assess whether Hoxa1-399 functions in cellular differentiation, we analyzed
      Hoxb1, a Hoxa1 target gene. Hoxa1-993 and its cofactor, Pbx1, bind to the Hoxb1
      SOct-R3 promoter to transcriptionally activate a luciferase reporter. Results
      from F9 stem cells that stably express ectopic Hoxa1-399 (the F9-399 line) show
      that Hoxa1-399 reduces this transcriptional activation. Gel shift assays
      demonstrate that Hoxa1-399 reduces Hoxa1-993/Pbx1 binding to the Hoxb1 SOct-R3
      region. GST pull-down experiments suggest that Hoxa1-399, Hoxa1-993, and Pbx1
      form a trimer. However, the F9-399 line exhibits no differences in RA-induced
      proliferation arrest or endogenous Hoxb1, Pbx1, Hoxa5, Cyp26a1, GATA4, or Meis
      mRNA levels when compared to F9 wild-type.

PMID- 19115253
TI  - Protein kinase-A affects sorting and conformation of the sodium-dependent glucose
      co-transporter SGLT1.
AB  - In Chinese hamster ovary cells expressing rabbit sodium-dependent glucose
      transporter (rbSGLT1) protein kinase A (PKA) activators (forskolin and 8-Br-cAMP)
      stimulated alpha-methyl D-glucopyranoside uptake. Kinetic analysis revealed an
      increase in both V(max) and affinity of the transport. Immunohistochemistry and
      biotinylation experiments showed that this stimulation was accompanied by an
      increased amount of SGLT1 localized into the plasma membrane, which explains the
      higher V(max) of the transport. Cytochalasin D only partly attenuated the effect
      of forskolin as did deletion of the PKA phosphorylation site of SGLT1 in
      transient transfection studies. Experiments using an anti-phosphopeptide antibody
      revealed that forskolin also increased the extent of phosphorylation of SGLT1 in
      the membrane fraction. These results suggested that regulation of SGLT1 mediated
      glucose transport involves an additional direct effect on SGLT1 by
      phosphorylation. To evaluate this assumption further, phosphorylation studies of
      recombinant human SGLT1 (hSGLT1) in vitro were performed. In the presence of the
      catalytic subunit PKA and [(32)P] ATP 1.05 mol of phosphate were incorporated/mol
      of hSGLT1. Additionally, phosphorylated hSGLT1 demonstrated a reduction in
      tryptophan fluorescence intensity and a higher quenching by the hydrophilic Trp
      quencher acrylamide, particularly in the presence of D-glucose. These results
      indicate that PKA-mediated phosphorylation of SGLT1 changes the conformation of
      the empty carrier and the glucose carrier complex, probably causing the increase
      in transport affinity. Thus, PKA-mediated phosphorylation of the transporter
      represents a further mechanism in the regulation of SGLT1-mediated glucose
      transport in epithelial cells, in addition to a change in surface membrane
      expression.

PMID- 19115256
TI  - Insecticidal activities of leaf and twig essential oils from Clausena excavata
      against Aedes aegypti and Aedes albopictus larvae.
AB  - BACKGROUND: The current study investigates, for the first time, the mosquito
      larvicidal activities of leaf and twig essential oils from Clausena excavata
      Burm. f. and their individual constituents against Aedes aegypti L. and Aedes
      albopictus Skuse larvae. The yields of essential oils obtained from
      hydrodistillation were compared, and their constituents were determined by GC-MS
      analyses. RESULTS: The LC(50) values of leaf and twig essential oils against
      fourth-instar larvae of Ae. aegypti and Ae. albopictus were 37.1-40.1 microg mL(
      1) and 41.1-41.2 microg mL(-1) respectively. This study demonstrated that C.
      excavata leaf and twig essential oils possess mosquito larvicidal activity,
      inhibiting the growth of mosquito larvae for both species at a low concentration.
      In addition, results of larvicidal assays showed that the effective constituents
      in leaf and twig essential oils were limonene, gamma-terpinene, terpinolene, beta
      myrcene, 3-carene and p-cymene. The LC(50) values of these constituents against
      both mosquito larvae were below 50 microg mL(-1). Among these effective
      constituents, limonene had the best mosquito larvicidal activity, with LC(50) of
      19.4 microg mL(-1) and 15.0 microg mL(-1) against Ae. aegypti and Ae. albopictus
      larvae respectively. CONCLUSION: The findings suggested that the essential oils
      from Clausena excavata leaf and twig and their effective constituents may be
      explored as a potential natural larvicide.

PMID- 19115254
TI  - PPARgamma2 nuclear receptor controls multiple regulatory pathways of osteoblast
      differentiation from marrow mesenchymal stem cells.
AB  - Rosiglitazone (Rosi), a member of the thiazolidinedione class of drugs used to
      treat type 2 diabetes, activates the adipocyte-specific transcription factor
      peroxisome proliferator-activated receptor gamma (PPARgamma). This activation
      causes bone loss in animals and humans, at least in part due to suppression of
      osteoblast differentiation from marrow mesenchymal stem cells (MSC). In order to
      identify mechanisms by which PPARgamma2 suppresses osteoblastogenesis and
      promotes adipogenesis in MSC, we have analyzed the PPARgamma2 transcriptome in
      response to Rosi. A total of 4,252 transcriptional changes resulted when Rosi (1
      microM) was applied to the U-33 marrow stromal cell line stably transfected with
      PPARgamma2 (U-33/gamma2) as compared to non-induced U-33/gamma2 cells.
      Differences between U-33/gamma2 and U-33 cells stably transfected with empty
      vector (U-33/c) comprised 7,928 transcriptional changes, independent of Rosi.
      Cell type-, time- and treatment-specific gene clustering uncovered distinct
      patterns of PPARgamma2 transcriptional control of MSC lineage commitment. The
      earliest changes accompanying Rosi activation of PPARgamma2 included effects on
      Wnt, TGFbeta/BMP and G-protein signaling activities, as well as sustained
      induction of adipocyte-specific gene expression and lipid metabolism. While
      suppression of osteoblast phenotype is initiated by a diminished expression of
      osteoblast-specific signaling pathways, induction of the adipocyte phenotype is
      initiated by adipocyte-specific transcriptional regulators. This indicates that
      distinct mechanisms govern the repression of osteogenesis and the stimulation of
      adipogenesis. The co-expression patterns found here indicate that PPARgamma2 has
      a dominant role in controlling osteoblast differentiation and suggests numerous
      gene-gene interactions that could lead to the identification of a "master"
      regulatory scheme directing this process.

PMID- 19115255
TI  - Patients' attitudes of dementia screening across the Atlantic.
AB  - BACKGROUND: Dementia is a common and growing global public health problem. It
      leads to a high burden of suffering for society with an annual cost of $100
      billion in the US and $10 billion in the UK. New strategies for both treatment
      and prevention of dementia are currently being developed. Implementation of these
      strategies will depend on the presence of a viable community or primary care
      based dementia screening and diagnosis program and patient acceptance of such a
      program. OBJECTIVE: To compare the acceptance, perceived harms and perceived
      benefits of dementia screening among older adults receiving their care in two
      different primary health care systems in two countries. DESIGN: A Cross-sectional
      study. SETTING: Primary care clinics in Indianapolis, USA and Kent, UK.
      PARTICIPANTS: A convenience sample of 245 older adults (Indianapolis, n = 125;
      Kent, n = 120). OUTCOMES: Acceptance of dementia screening and its perceived
      harms and benefits as determined by a 52-item questionnaire (PRISM-PC
      questionnaire). RESULTS: Four of the five domains were significantly different
      across the two samples. The UK sample had significantly higher dementia screening
      acceptance scores (p < 0.05); higher perceived stigma scores (p < 0.05); higher
      perceived loss of independence scores (p < 0.01); and higher perceived suffering
      scores (p < 0.01) than the US sample. Both groups perceived dementia screening as
      beneficial (p = 0.218). After controlling for prior experience with dementia,
      acceptance and stigma were marginalized. CONCLUSIONS: Older adults attending
      primary care clinics across the Atlantic value dementia screening but have
      significant concerns about dementia screening although these concerns differed
      between the two countries. Low acceptance rates and high rates of perceived harms
      might be a significant barrier for the introduction of treatment or preventive
      methods for dementia in the future.

PMID- 19115258
TI  - Mechanisms of prostate cancer cell survival after inhibition of AR expression.
AB  - Recent reports have shown that the AR is the key determinant of the molecular
      changes required for driving prostate cancer cells from an androgen-dependent to
      an androgen-independent or androgen depletion-independent (ADI) state. Several
      recent publications suggest that down-regulation of AR expression should
      therefore be considered the principal strategy for the treatment of ADI prostate
      cancer. However, no valid data is available about how androgen-dependent prostate
      cancer cells respond to apoptosis-inducing drugs after knocking down AR
      expression and whether prostate cancer cells escape apoptosis after inhibition of
      AR expression. This review will focus on mechanisms of prostate cancer cell
      survival after inhibition of AR activity mediated either by androgen depletion or
      by targeting the expression of AR by siRNA. We have shown that knocking down AR
      expression by siRNA induced PI3K-independent activation of Akt, which was
      mediated by calcium/calmodulin-dependent kinase II (CaMKII). We also showed that
      the expression of CaMKII genes is under AR control: active AR in the presence of
      androgens inhibits CaMKII gene expression whereas inhibition of AR activity
      results in an elevated level of kinase activity and in enhanced expression of
      CaMKII genes. This in turn activates the anti-apoptotic PI3K/Akt pathways. CaMKII
      also express anti-apoptotic activity that is independent from the Akt pathway.
      This may therefore be an important mechanism by which prostate cancer cells
      escape apoptosis after androgen depletion or knocking down AR expression. In
      addition, we have found that there is another way to escape cell death after AR
      inhibition: DNA damaging agents cannot fully activate p53 in the absence of AR
      and as a result p53 down stream targets, for example, microRNA-34, cannot be
      activated and induce apoptosis. This implies that there may be a need for re
      evaluation of the therapeutic approaches to human prostate cancer.

PMID- 19115257
TI  - Cell surface heparan sulfate released by heparanase promotes melanoma cell
      migration and angiogenesis.
AB  - Heparan sulfate (HS) proteoglycans are essential components of the cell-surface
      and extracellular matrix (ECM) which provide structural integrity and act as
      storage depots for growth factors and chemokines, through their HS side chains.
      Heparanase (HPSE) is the only mammalian endoglycosidase known that cleaves HS,
      thus contributing to matrix degradation and cell invasion. The enzyme acts as an
      endo-beta-D-glucuronidase resulting in HS fragments of discrete molecular weight
      size. Cell-surface HS is known to inhibit or stimulate tumorigenesis depending
      upon size and composition. We hypothesized that HPSE contributes to melanoma
      metastasis by generating bioactive HS from the cell-surface to facilitate
      biological activities of tumor cells as well as tumor microenvironment. We
      removed cell-surface HS from melanoma (B16B15b) by HPSE treatment and resulting
      fragments were isolated. Purified cell-surface HS stimulated in vitro B16B15b
      cell migration but not proliferation, and importantly, enhanced in vivo
      angiogenesis. Furthermore, melanoma cell-surface HS did not affect in vitro
      endothelioma cell (b.End3) migration. Our results provide direct evidence that,
      in addition to remodeling ECM and releasing growth factors and chemokines, HPSE
      contributes to aggressive phenotype of melanoma by releasing bioactive cell
      surface HS fragments which can stimulate melanoma cell migration in vitro and
      angiogenesis in vivo.

PMID- 19115259
TI  - Effects of age and gender on WNT gene expression in human bone marrow stromal
      cells.
AB  - WNT signaling pathways play important roles in the behavior of human bone marrow
      stromal cells. Although WNT expression has been examined in human bone marrow
      stromal cells (hMSCs) with limited numbers of subjects or from commercial
      sources, there are conflicting results on WNT gene expression in hMSCs.
      Furthermore, the effects of age and gender on WNT expression in hMSCs are largely
      unknown. In this study, we evaluated RNA expression of all the WNT genes in hMSCs
      from 19 subjects, 12 women and 7 men, aged from 36 to 85 years. Analysis of WNT
      gene expression in young and old groups indicated that WNT7B and 14 were
      expressed significantly higher in the young group. WNT2 and WNT13 showed a trend
      of higher expression in young group. WNT7B, 13, and 14 were inversely correlated
      with age. Further analysis for gender-specific difference indicated that WNT16
      was expressed significantly higher in men than in women. WNT11 showed a trend of
      higher expression in hMSCs from women. For the hMSCs from women, WNT13 was
      inversely correlated with age and WNT4 was positively correlated with age. For
      the hMSCs from men, WNT7B and WNT14 were inversely correlated with age. These
      data indicated that most of the age-related WNT genes belong to the canonical WNT
      signaling pathway. Further, there are gender-specific differences in the
      expression of WNT4, 7B, 13, 14, and 16 in hMSCs. Age and gender account for many
      of the sample-to-sample variations in WNT gene expression in human marrow stromal
      cells.

PMID- 19115260
TI  - Transcriptional regulation of human eosinophil RNase2 by the liver-enriched
      hepatocyte nuclear factor 4.
AB  - Human eosinophil-derived neurotoxin (EDN, RNase2) and eosinophil cationic protein
      (ECP, RNase3) sequences possess as high as 92% identity in their promoter
      regions. The major difference within this region is a 34-nucleotide (34-nt)
      segment appeared only in the edn promoter. In addition, six discrete segments
      existed in the regulatory regions of both edn and ecp. Our previous study
      indicated that the 34-nt segment is responsive for higher transcription activity
      of edn in comparison with ecp, via binding to transcription activator Sp1. In
      this study, the roles of the six discrete segments in transcription regulation
      were investigated and the -350/-329 region (ednR2) was shown to be involved in
      the regulation of edn expression. When the ednR2 segment of edn was replaced with
      that of ecp, a significant decrease in edn promoter activity was detected.
      Supershift, chromatin immunoprecipitation, and DNA affinity precipitation assays
      further showed that a transcription factor HNF4 bound to the ednR2 region of edn
      promoter in vitro. Interestingly, HNF4 overexpression resulted in the reduction
      of edn promoter activity in HepG2 cells, due to involvement of both ednR2 and the
      34-nt regions, and direct interaction between HNF4 and Sp1, which abolishes Sp1
      binging to the 34-nt segment. Moreover, when the Sp1 was depleted in the cell,
      overexpressed HNF4 enhanced edn promoter activity. Our results provide novel
      mechanisms for HNF4 function as an activator to regulate edn promoter activity,
      which account for differential transcription regulation of human eosinophil
      RNases.

PMID- 19115262
TI  - Fetal crown-rump length and estimation of gestational age in an ethnic Chinese
      population.
AB  - OBJECTIVES: To develop a sonographic dating formula based on fetal crown-rump
      length (CRL) in a Hong Kong Chinese population, quantify its systematic
      prediction error and compare its performance with established dating formulae.
      METHODS: This was a prospective observational study of women with a spontaneously
      conceived singleton pregnancy and a regular menstrual cycle in the preceding 12
      month period. Ultrasound examinations were performed at gestational ages ranging
      from 6 to 15 + 6 weeks according to menstrual dates. The CRL of each fetus was
      measured three times, the mean of which was used to derive the best-fit
      fractional polynomial regression model for estimation of gestational age in
      relation to CRL. For each fetus, the menstrual age was compared to the
      gestational age calculated using three established dating formulae based on CRL
      measurement. The mean of the differences between estimated and menstrual age was
      calculated for each formula. RESULTS: Of the 394 subjects recruited one was
      excluded as the pregnancy resulted in intrauterine demise. The best-fit equation
      for the sonographic estimate of gestational age (GA, in days) from CRL (in mm)
      was GA = 26.643 + 7.822 x CRL(1/2)(R(2) = 0.96). The mean difference between
      menstrual age and the predicted gestational age was 0.22 days (95% CI, - 0.14 to
      0.56), which was lower than that of the three established CRL dating formulae.
      CONCLUSION: We have derived a formula suitable for the dating of naturally
      conceived pregnancies between 6 and 15 weeks of gestation that has no systematic
      prediction error (the 95% CI of mean difference between predicted and menstrual
      age included zero), comparing favorably with established CRL dating formulae.

PMID- 19115263
TI  - Pregnancy outcome after ultrasound diagnosis of fetal intra-abdominal umbilical
      vein varix.
AB  - OBJECTIVES: Fetal intra-abdominal umbilical vein (FIUV) varix is a focal
      dilatation of the intra-abdominal portion of the umbilical vein, which has been
      reported to be associated with intrauterine death and other anomalies. Our aim
      was to examine our experience with this diagnosis at a single tertiary-care
      center and to correlate it with clinical outcome. METHODS: This was a
      retrospective case series study. Our ultrasound database was searched for all
      cases with a diagnosis of FIUV varix identified at our facility between 1997 and
      2007. We reviewed all ultrasound examinations, maternal antenatal records,
      delivery records and newborns' medical records. RESULTS: We identified 52 cases
      of FIUV among a population of approximately 68,000. Three cases of trisomy 21
      were identified, all of which were accompanied by other anomalies. There was
      intrauterine death of one fetus with trisomy 21 at 35 weeks of gestation. We did
      not find an association between FIUV varix and other obstetric complications.
      CONCLUSIONS: The outcome of pregnancies with FIUV varix is generally favorable.
      The finding of a FIUV varix should prompt the search for other anomalies,
      especially markers of aneuploidy.

PMID- 19115268
TI  - Nonlinear effects in asymmetric catalysis.
AB  - There is a need for the preparation of enantiomerically pure compounds for
      various applications. An efficient approach to achieve this goal is asymmetric
      catalysis. The chiral catalyst is usually prepared from a chiral auxiliary, which
      itself is derived from a natural product or by resolution of a racemic precursor.
      The use of non-enantiopure chiral auxiliaries in asymmetric catalysis seems
      unattractive to preparative chemists, since the anticipated enantiomeric excess
      (ee) of the reaction product should be proportional to the ee value of the chiral
      auxiliary (linearity). In fact, some deviation from linearity may arise. Such
      nonlinear effects can be rich in mechanistic information and can be synthetically
      useful (asymmetric amplification). This Review documents the advances made during
      the last decade in the use of nonlinear effects in the area of organometallic and
      organic catalysis.

PMID- 19115269
TI  - Insulin induces the low density lipoprotein receptor-related protein 1 (LRP1)
      degradation by the proteasomal system in J774 macrophage-derived cells.
AB  - Low-density lipoprotein receptor-related protein 1 (LRP1) is an endocytic
      receptor, which binds and internalizes diverse ligands such as activated alpha(2)
      macroglobulin (alpha(2)M*). LRP1 promotes intracellular signaling, which
      downstream mediates cellular proliferation and migration of different types of
      cells, including macrophages. Unlike the LDL receptor, LRP1 expression is not
      sensitive to cellular cholesterol levels but appears to be responsive to insulin.
      It has been previously demonstrated that insulin increases the cell surface
      presentation of LRP1 in adipocytes and hepatocytes, which is mediated by the
      intracellular PI(3)K/Akt signaling activation. The LRP1 protein distribution is
      similar to other insulin-regulated cell surface proteins, including transferring
      receptor (Tfr). However, in macrophages, the insulin effect on the LRP1
      distribution and expression is not well characterized. Considering that
      macrophages play a central role in the pathogenesis of atherosclerosis, herein we
      evaluate the effect of insulin on the cellular expression of LRP1 in J774
      macrophages-derived cells using Western blot and immunofluorescence microscopy.
      Our data demonstrate that insulin induces a significant decrease in the LRP1
      protein content, without changing the specific mRNA level of this receptor.
      Moreover, insulin specifically affected the protein expression of LRP1 but not
      Tfr. The insulin-induced protein degradation of LRP1 in J774 cells was mediated
      by the activation of the PI(3)K/Akt pathway and proteasomal system by an enhanced
      ubiquitin-receptor conjugation. The decreased content of LRP1 induced by insulin
      affected the cellular internalization of alpha(2)M*. Thus, we propose that the
      protein degradation of LRP-1 induced by insulin in macrophages could have
      important effects on the pathogenesis of atherosclerosis.

PMID- 19115274
TI  - The state of the art of chemical biology.

PMID- 19115277
TI  - Interfaces: two worlds unite.

PMID- 19115278
TI  - From Chem. Eur. J. to ChemSusChem: all from ChemPubSoc Europe.

PMID- 19115279
TI  - In silico prediction of drug solubility: 4. Will simple potentials suffice?
AB  - In view of the extreme importance of reliable computational prediction of aqueous
      drug solubility, we have established a Monte Carlo simulation procedure which
      appears, in principle, to yield reliable solubilities even for complex drug
      molecules. A theory based on judicious application of linear response and mean
      field approximations has been found to reproduce the computationally demanding
      free energy determinations by simulation while at the same time offering
      mechanistic insight. The focus here is on the suitability of the model of both
      drug and solvent, i.e., the force fields. The optimized potentials for liquid
      simulations all atom (OPLS-AA) force field, either intact or combined with
      partial charges determined either by semiempirical AM1/CM1A calculations or taken
      from the condensed-phase optimized molecular potentials for atomistic simulation
      studies (COMPASS) force field has been used. The results illustrate the crucial
      role of the force field in determining drug solubilities. The errors in
      interaction energies obtained by the simple force fields tested here are still
      found to be too large for our purpose but if a component of this error is
      systematic and readily removed by empirical adjustment the results are
      significantly improved. In fact, consistent use of the OPLS-AA Lennard-Jones
      force field parameters with partial charges from the COMPASS force field will in
      this way produce good predictions of amorphous drug solubility within 1 day on a
      standard desktop PC. This is shown here by the results of extensive new
      simulations for a total of 47 drug molecules which were also improved by
      increasing the water box in the hydration simulations from 500 to 2000 water
      molecules.

PMID- 19115280
TI  - Predicting PH vibrations of gas phase molecules and surface-adsorbed species
      using bond length-frequency correlations.
AB  - The high frequency XH (e.g., X = C, Si) stretching modes in small molecules are
      only slightly perturbed by other vibrational modes present in the system. The
      isolated frequencies, in these cases, exhibit a linear relationship with the
      corresponding bond lengths. Here, we study such a bond length-frequency
      correlation in the case of PH stretching vibrations for molecules in the gas
      phase as well as for surface-adsorbed species. Although a high degree of linear
      correlation is found, there is a small dependence on the local coordination
      around P, leading to significant deviations in some cases. By a careful analysis,
      we show that such correlations can be used to predict new surface frequencies
      without computing the Hessian matrix explicitly.

PMID- 19115281
TI  - Prediction of human cytochrome P450 2B6-substrate interactions using hierarchical
      support vector regression approach.
AB  - The human cytochrome P450 2B6 can metabolize a number of clinical drugs.
      Inhibition of CYP2B6 by coadministered multiple drugs may lead to drug-drug
      interactions and undesired drug toxicity. The aim of this investigation is to
      develop an in silico model to predict the interactions between P450 2B6 and novel
      inhibitors using a novel hierarchical support vector regression (HSVR) approach,
      which simultaneously takes into account the coverage of applicability domain (AD)
      and the level of predictivity. Thirty-seven molecules were deliberately selected
      and rigorously scrutinized from the literature data, of which 26 and 11 molecules
      were treated as the training set and the test set to generate the models and to
      validate the generated models, respectively. The generated HSVR model gave rise
      to an r2 value of 0.97 for observed versus predicted pK(m) values for the
      training set, a q2 value of 0.93 by the 10-fold cross-validation, and an r2 value
      of 0.82 for the test set. Additionally, the predicted results show that the HSVR
      model outperformed the individual local models, the global model, and the
      consensus model. Thus, this HSVR model provides an accurate tool for the
      prediction of human cytochrome P450 2B6-substrate interactions and can be
      utilized as a primary filter to eliminate the potential selective inhibitor of
      CYP2B6.

PMID- 19115282
TI  - Electronic structures and optical properties of BiOX (X = F, Cl, Br, I) via DFT
      calculations.
AB  - Based on the density functional theory (DFT), the lattice constants and atomic
      positions of BiOX (X = F, Cl, Br, I) species have been optimized, and the
      electronic and optical properties of the relaxed species have been calculated,
      with Bi 5d states considered or not. Relaxation generally results in the
      shrinkage in a and the expansion of c. Relaxed BiOCl, BiOBr, and BiOI present
      indirect band gaps, whereas BiOF exhibits a direct or somewhat indirect band-gap
      feature corresponding to the relaxation and calculation with the Bi 5d states or
      not. The bottom of the conduction band is quite flat for relaxed BiOI, and
      apparently flat in BiOBr, and shows observable flatness in BiOCl as well when
      considering the Bi 5d states. The top of the valence band is rather even as well
      for some species. The obtained maximum gaps for relaxed BiOF, BiOCl, BiOBr, and
      BiOI are 3.34, 2.92, 2.65, and 1.75 eV, respectively. The density peak of X np
      states in the valence band shifts toward the valence band maximum with the
      increasing X atomic number. The bandwidths, atomic charges, bond orders, and
      orbital density have also been investigated along with some optical properties.

PMID- 19115283
TI  - Investigation of chemical bond characteristics, thermal expansion coefficients
      and bulk moduli of alpha-R2MoO6 and R2Mo2O7 (R = rare earths) by using a
      dielectric chemical bond method.
AB  - Theoretical researches are performed on the alpha-R2MoO6 (R = Y, Gd, Tb Dy, Ho,
      Er, Tm and Yb) and pyrochlore-type R2Mo2O7 (R = Y, Nd, Sm, Gd, Tb and Dy) rare
      earth molybdates by using chemical bond theory of dielectric description. The
      chemical bonding characteristics and their relationship with thermal expansion
      property and compressibility are explored. The calculated values of linear
      thermal expansion coefficient (LTEC) and bulk modulus agree well with the
      available experimental values. The calculations reveal that the LTECs and the
      bulk moduli do have linear relationship with the ionic radii of the lanthanides:
      the LTEC decreases from 6.80 to 6.62 10(-6)/K and the bulk modulus increases from
      141 to 154 GPa when R goes in the order Gd, Tb Dy, Ho, Er, Tm, and Yb in the
      alpha-R2MoO6 series; while in the R2Mo2O7 series, the LTEC ranges from 6.80 to
      6.61 10(-6)/K and the bulk modulus ranges from 147 to 163 GPa when R varies in
      the order Nd, Sm, Gd, Tb and Dy.

PMID- 19115284
TI  - Defects in intracellular trafficking and endocytic/vacuolar acidification
      determine the efficiency of endocytotic DNA uptake in yeast.
AB  - The yeast Saccharomyces cerevisiae is a standard model system to study
      endocytosis. Here we describe the examination of a representative subset of
      deletion mutants to identify and locate steps in endocytic transport,
      endosomal/lysosomal acidification and in intracellular transport of hydrolases in
      non-viral transfection processes. When transport in late endocytosis is
      inhibited, transfection efficiency is significantly enhanced. Similarly,
      transfection efficiency is enhanced when the pH-value of the endosomal/vacuolar
      system is modified. Transfection efficiency is furthermore elevated when the
      N+/K+ transport in the endosomal system is disturbed. Finally, we observe
      enhanced transfection efficiency in mutants disturbed in the CVT/autophagy
      pathway and in hydrolase transport to the vacuole. In summary, non-viral
      transfection efficiency can be significantly increased by either (i) inhibiting
      the transport of endocytosed material before it enters the vacuole, or (ii)
      inducing a non-natural pH-value of the endosomal/vacuolar system, or (iii)
      slowing down degradative processes by inhibiting vacuolar hydrolases or the
      transport between Golgi and late endosome/vacuole.

PMID- 19115286
TI  - Solid-state gas sensors developed from functional difluoroboradiazaindacene dyes.
AB  - This article describes the synthesis and characterization of several new
      difluoroboradiazaindacene (BODIPY) dyes functionalized at the central 8-position
      by a phenyliodo, phenylheptynoate or phenylheptynoic fragment and at the 3- or
      3/5-position(s) by 4-dimethylaminophenylstyryl residue(s). Single-crystal
      structural determinations confirm the planarity of the dyes, while the absorption
      and fluorescence spectroscopic properties are highly sensitive to the state of
      protonation (or alkylation) of the terminal anilino donor group(s). Reversible
      color tuning from green to blue for absorption and from colorless (i.e., near-IR
      region) to red for fluorescence is obtained on successive addition of acid and
      base. The difunctionalized derivative is especially interesting in this respect
      and shows two well-resolved pK(a) values of 5.10 and 3.04 in acetonitrile.
      Addition of the first proton causes only small spectral changes and deactivates
      the molecule towards addition of the second proton. It is this latter step that
      accommodates the large change in absorption and emission properties, due to the
      reversible extinction of the intramolecular charge-transfer character inherent to
      this type of dye. The main focus of the work is the covalent anchoring of the
      dyes to inert, porous polyacrylate beads so as to form a solid-state sensor
      suitable for analysis of gases or flowing liquids. The final material is highly
      stable--its performance is undiminished after more than one year--and fully
      reversible over many cycles. The sensitivity is such that reactions can be
      followed by the naked eye and the detection limit is about 600 ppb for HCl and
      about 80 ppb for ammonia. Trace amounts of diphosgene can be detected, as can
      alkylating agents. The sensing action is indiscriminate and also operates when
      the beads are dispersed in aqueous media.

PMID- 19115285
TI  - Regio- and chemoselective metalation of chloropyrimidine derivatives with TMPMgCl
      x LiCl and TMP(2)Zn x 2 MgCl(2) x 2 LiCl.
AB  - Efficient zincation and magnesiation of chlorinated pyrimidines can be performed
      at convenient temperatures (e.g., 25 and 55 degrees C) by using TMPMgCl x LiCl
      and TMP(2)Zn x 2 MgCl(2) x 2 LiCl (TMP = 2,2,6,6-tetramethylpiperidyl) as
      effective bases. Quenching of the resulting zincated or magnesiated pyrimidines
      with various electrophiles furnishes highly functionalized pyrimidines in 51-93%
      yield. Oxidative aminations were carried out, thus leading to aminated
      pyrimidines. By using this methodology, we have also prepared pharmaceutically
      relevant pyrazolopyrimidines and the fungicide Mepanipyrim.

PMID- 19115287
TI  - Phosphine-free, palladium-catalyzed arylation of heterocycles through C-H bond
      activation with pivalic acid as a cocatalyst.

PMID- 19115288
TI  - C80Cl12: a chlorine derivative of the chiral D2-C80 isomer--empirical rationale
      of halogen-atom addition pattern.
AB  - Welcome to the family! The constitution of the chiral D(2)-C(80) fullerene has
      been confirmed through single-crystal X-ray analysis of the chlorinated
      C(80)Cl(12). The addition pattern of the chlorine atoms in the structure of
      C(80)Cl(12) together with other structures of halogenated higher fullerenes is
      discussed. A stepwise principle of higher fullerene reactivity is proposed.
      Unusual short intermolecular chlorine-chlorine contacts are reported.

PMID- 19115289
TI  - Electrochemically driven sequential machines: an implementation of copper
      rotaxanes.

PMID- 19115290
TI  - Negishi cross-couplings compatible with unprotected amide functions.

PMID- 19115292
TI  - FeNCN and Fe(NCNH)2: synthesis, structure, and magnetic properties of a nitrogen
      based pseudo-oxide and -hydroxide of divalent iron.
AB  - Iron man challenge: Iron carbodiimide, FeNCN, and its precursor iron
      (bis)monohydrocyanamide, Fe(NCNH)(2), have been synthesized and physically
      characterized. Both FeNCN and Fe(NCNH)(2) exhibit nitrogen-mediated
      antiferromagnetic superexchange interactions with reduced magnetic moments very
      similar, but not identical, to the correlated 3d oxides.

PMID- 19115291
TI  - A fluorescent bisanthracene macrocycle discriminates between matched and mismatch
      containing DNA.

PMID- 19115293
TI  - Hetero-seeding and solid mixture to obtain new crystalline forms.
AB  - Para-methyl benzyl alcohol (p-MeBA II) and para-chloro benzyl alcohol (p-ClBA)
      are quasi-isostructural and share the same hydrogen-bond patterns, but their
      crystals are not isomorphous. No new polymorphs could be obtained by conventional
      polymorph screening based on different solvents and different crystallization
      conditions. Formation of a new polymorph of p-MeBA named p-MeBA I, isomorphous
      with the crystal of p-ClBA, was induced by hetero-seeding with a small quantity
      of powdered p-ClBA added to a supersaturated solution of p-MeBA in hexane, while
      seeding of p-ClBA with p-MeBA II failed to give a new phase of p-ClBA isomorphous
      with known crystalline p-MeBA II. Mixed crystals of p-MeBA and p-ClBA were also
      prepared with different p-MeBA/p-ClBA ratios to understand the role of the
      different functional groups in the crystal structure. Crystal phases were
      characterized by combined use of single-crystal and powder X-ray diffraction,
      differential scanning calorimetry, and solid-state NMR spectroscopy.

PMID- 19115295
TI  - Effect of doped transition metal on reversible hydrogen release/uptake from
      NaAlH4.
AB  - Periodic density functional theory calculations with plane-wave basis set and
      projector-augmented wave potentials have been carried out to investigate the
      stability and hydrogen interaction in the NaAlH(4)(001) surfaces doped with 3d
      transition-metal (TM) elements. A complex structure, TMAl(3)H(12), in which the
      TM atom occupies the interstitial position formed from three AlH(4)(-) groups, is
      the most stable structure for TM = Sc to Co. The stability of the complex
      structure, as well as the hydrogen desorption energies from different positions
      of the complex structure, was found to follow the 18-electron rule in general.
      The electron-deficient TMAl(3)H(x) tends to get more electrons by coordinating
      with the surrounding Al-H bonds and H-H bond, or by losing the "outside" hydrogen
      atoms. On the other hand, the electron-rich complex loses its excess electrons
      easily by releasing AlH(x), which resulted in the formation of a new catalytic
      center, or by desorbing H(2). By cycling between the electron-deficient and
      electron-rich states, TMAl(3)H(x) acted as an active center in reversible
      hydrogen release/uptake processes. Electronic structure analysis revealed that
      the electron transfer between hydrogen and Al groups mediated by the d orbitals
      of TMs played important roles in hydrogen release/uptake from alanate-based
      materials. The exchange of ligands can be described as a sigma-bond metathesis
      process catalyzed by transition metals through a dihydrogen complex. Early
      transition metals are more efficient to reduce hydrogen desorption energy and
      break H-H and Al-H bonds as a result of balanced electron-accepting/backdonating
      abilities, making them better candidates as catalysts. The present analyses are
      consistent with the experimental observations.

PMID- 19115294
TI  - Organic ligand binding by a hydrophobic cavity in a designed tetrameric coiled
      coil protein.
AB  - The design and characterization of a hydrophobic cavity in de novo designed
      proteins provides a wide range of information about the functions of de novo
      proteins. We designed a de novo tetrameric coiled-coil protein with a hydrophobic
      pocketlike cavity. Tetrameric coiled coils with hydrophobic cavities have
      previously been reported. By replacing one Leu residue at the a position with
      Ala, hydrophobic cavities that did not flatten out due to loose peptide chains
      were reliably created. To perform a detailed examination of the ligand-binding
      characteristics of the cavities, we originally designed two other coiled-coil
      proteins: AM2, with eight Ala substitutions at the adjacent a and d positions at
      the center of a bundled structure, and AM2W, with one Trp and seven Ala
      substitutions at the same positions. To increase the association of the helical
      peptides, each helical peptide was connected with flexible linkers, which
      resulted in a single peptide chain. These proteins exhibited CD spectra
      corresponding to superhelical structures, despite weakened hydrophobic packing.
      AM2W exhibited binding affinity for size-complementary organic compounds. The
      dissociation constants, K(d), of AM2W were 220 nM for adamantane, 81 microM for 1
      adamantanol, and 294 microM for 1-adamantaneacetic acid, as measured by
      fluorescence titration analyses. Although it was contrary to expectations, AM2
      did not exhibit any binding affinity, probably due to structural defects around
      the designed hydrophobic cavity. Interestingly, AM2W exhibited incremental
      structure stability through ligand binding. Plugging of structural defects with
      organic ligands would be expected to facilitate protein folding.

PMID- 19115296
TI  - Protein flexibility and metal coordination changes in DHAP-dependent aldolases.
AB  - The mobility of rhamnulose-1-phosphate aldolase (RhuA) was analysed with a normal
      mode description and high level calculations on models of the active site. We
      report the connection between the mobility and the chemical properties of the
      active site, and compare them to a closely related enzyme, fuculose-1-phosphate
      aldolase (FucA). Calculations show that the different coordination number for the
      zinc ion, reported in the crystal structures of RhuA and FucA, was due to a
      different spatial arrangement of the residues, not to their different chemical
      nature. Moreover, the metal coordination change is correlated with activity. The
      domain mobility of the enzyme can reshape the active site of RhuA into the
      arrangement found in the FucA structure, and vice-versa. This has a direct
      influence on the energy barrier for the aldol reaction catalyzed by these
      enzymes, thus showing a coupling of the domain movements and the catalytic
      effects. Hence domain movements and the coordination chemistry of the active site
      metal suggest an explanation of why these enzymes have similar experimental
      turnover rates.

PMID- 19115297
TI  - Bi2O3 hierarchical nanostructures: controllable synthesis, growth mechanism, and
      their application in photocatalysis.
AB  - By introducing VO(3)(-) into the reaction system, uniform hierarchical
      nanostructures of Bi(2)O(3) have been successfully synthesized by a template-free
      aqueous method at 60-80 degrees C for 6 h. The as-prepared hierarchitectures are
      composed of 2D nanosheets, which intercross with each other. Based on the
      electron microscope observations, the growth of such hierarchitectures has been
      proposed as an Ostwald ripening process followed by self-assembly. The
      nucleation, growth, and self-assembly of Bi(2)O(3) nanosheets could be readily
      tuned, which brought different morphologies and microstructures to the final
      products. Pore-size distribution analysis revealed that both mesopores and
      macropores existed in the product. UV-vis spectroscopy was employed to estimate
      the band gap energies of the hierarchical nanostructures. The photocatalytic
      activities of as-prepared Bi(2)O(3) hierarchitectures were 6-10 times higher than
      that of the commercial sample, which was evaluated by the degradation of RhB dye
      under visible light irradiation (lambda>420 nm).

PMID- 19115298
TI  - Insights into structure direction of microporous aluminophosphates: competition
      between organic molecules and water.
AB  - A combination of experimental characterisation techniques and computational
      modelling has allowed us to gain insight into the molecular features governing
      structure direction in the synthesis of microporous aluminophosphates. The
      occlusion of three different structure-directing agents (SDAs), triethylamine
      (TEA), benzylpyrrolidine (BP) and (S)-(-)-N-benzylpyrrolidine-2-methanol (BPM),
      within the AFI structure during its crystallisation, together with the
      simultaneous incorporation of water, has been experimentally measured. We found a
      higher incorporation of organic molecules in the structure obtained with BPM,
      while a higher water (and lower organic) content is found for the ones obtained
      with TEA and BP as SDAs. The computational study provides a thermodynamic
      explanation for the observed behaviour in terms of the relative stabilisation
      energy of the SDAs and water molecules within the AFI framework compared with
      when they are in aqueous solution, and demonstrates that a competition for
      preferential occupation exists between water and organic SDAs, which is a
      function of the interaction with the inorganic framework. The lower interaction
      of TEA and BP molecules with the AFI structure promotes the simultaneous
      incorporation of water molecules in the 12-membered-ring (MR) channel, to
      increase the host-guest interaction energy and thus the thermodynamic stability.
      The presence of strongly interacting methanol groups in the BPM molecules leads
      to the incorporation of only organic molecules within the 12-MR channels. Our
      results demonstrate the essential role that water molecules play in the
      stabilisation of hydrophilic microporous aluminophosphates; a minimum amount of
      organic SDA is, however, essential for a templating role of the microporous
      architecture.

PMID- 19115299
TI  - Bio-inspired silicification on patterned surfaces generated by microcontact
      printing and layer-by-layer self-assembly.
AB  - Micropatterns of silica were generated under biocompatible conditions by a
      combination of microcontact printing (muCP), layer-by-layer (LbL) self-assembly,
      and biomimetic silicification. Quaternary amine-containing poly(diallyl dimethyl
      ammonium chloride) induced polycondensation of silicic acid, resulting in
      spatioselective formation of silica micropatterns. Scale bar: 10 microm.

PMID- 19115300
TI  - Oxidation of allyl alcohol in the presence of a gold catalyst: a route to 3
      hydroxypropionic acid.

PMID- 19115301
TI  - Physicochemical characterization of subporphyrazines--lower subphthalocyanine
      homologues.
AB  - Physicochemical characterization of boron(III) subporphyrazines (SubPzs)--lower
      subphthalocyanine (SubPc) homologues--has been carried out for the first time.
      The SubPz macrocycle can act both as an oxidizing and a reducing entity, giving
      rise to stable radical anion or radical cation species, respectively. SubPzs are
      luminescent and exhibit fluorescence quantum yields that are in the range known
      for SubPcs. The peripheral substitution plays a dramatic role with respect to the
      luminescence properties. Moreover, as with SubPcs, deactivation of the singlet
      excited state of the SubPzs by intersystem crossing affords long-lived triplet
      excited states, which are amenable to being used as singlet-oxygen generators.
      Subporphyrazines are also promising electro- and photoactive materials for
      molecular photovoltaics.

PMID- 19115302
TI  - Ethanol oxidation on electrocatalysts obtained by spontaneous deposition of
      palladium onto nickel-zinc materials.
AB  - Ni-Zn and Ni-Zn-P alloys supported on Vulcan XC-72 are effective materials for
      the spontaneous deposition of palladium through redox transmetalation with Pd(IV)
      salts. The materials obtained, Pd-(Ni-Zn)/C and Pd-(Ni-Zn-P)/C, have been
      characterized by a variety of techniques. The analytical and spectroscopic data
      show that the surface of Pd-(Ni-Zn)/C and Pd-(Ni-Zn-P)/C contain very small,
      highly dispersed, and highly crystalline palladium clusters as well as single
      palladium sites, likely stabilized by interaction with oxygen atoms from Ni--O
      moieties. As a reference material, a nanostructured Pd/C material was prepared by
      reduction of an aqueous solution of PdCl(2)/HCl with ethylene glycol in the
      presence of Vulcan XC-72. In Pd/C, the Pd particles are larger, less dispersed,
      and much less crystalline. Glassy carbon electrodes coated with the Pd-(Ni-Zn)/C
      and Pd-(Ni-Zn-P)/C materials, containing very low Pd loadings (22-25 microg cm(
      2)), were studied for the oxidation of ethanol in alkaline media in half cells
      and provided excellent results in terms of both specific current (as high as 3600
      A g(Pd)(-1) at room temperature) and onset potential (as low as -0.6 V vs
      Ag/AgCl/KCl(sat)).

PMID- 19115303
TI  - Sustainable synthesis of aldehydes, ketones or acids from neat alcohols using
      nitrogen dioxide gas, and related reactions.
AB  - Benzylic alcohols are quantitatively oxidized by gaseous nitrogen dioxide to give
      pure aromatic aldehydes. The reaction gas mixtures are transformed to nitric
      acid, which renders the processes free of waste. The exothermic gas-liquid or gas
      solid reactions profit from the solubility of nitrogen dioxide in the neat
      benzylic alcohols. The acid formed impedes further oxidation of the
      benzaldehydes. The neat isolated benzaldehydes and nitrogen dioxide
      quantitatively give the benzoic acids. Solid long-chain primary alcohols are
      directly and quantitatively oxidized with nitrogen dioxide gas to give the fatty
      acids in the solid state. The oxidations with ubiquitous nitrogen dioxide are
      extended to solid heterocyclic thioamides, which gives disulfides, and to
      diphenylamine, which gives tetraphenylhydrazine. These sustainable (green)
      specific oxidation procedures produce no dangerous residues from the oxidizing
      agent or from auxiliaries.

PMID- 19115304
TI  - Synthesis of bicyclic N-arylmethyl-substituted iminoribitol derivatives as
      selective nucleoside hydrolase inhibitors.
AB  - The purine metabolism of Trypanosoma and Leishmania spp. provides a good target
      in the search for new selective drugs. Bicyclic N-arylmethyl-substituted
      iminoribitols were developed as inhibitors of T. vivax nucleoside hydrolase, a
      key enzyme of the purine salvage pathway. The obtained results and structure
      activity data confirmed our model for inhibitor binding with a hydrogen bond
      between a nitrogen atom of the nucleobase mimetic and the protonated Asp40 from
      the enzyme. This interaction depends on an optimal pK(a) value, which can be
      influenced by the electronic properties of the substituents. These compounds are
      potent, selective inhibitors of nucleoside hydrolase and are inactive toward
      human nucleoside phosphorylase.

PMID- 19115305
TI  - Imidazole-annulated tetrathiafulvalenes exhibiting pH-tuneable intramolecular
      charge transfer and redox properties.
AB  - In order to study the electronic interactions in donor-acceptor ensembles as a
      function of pH, an efficient synthetic route to three imidazole-annulated
      tetrathiafulvalene (TTF) derivatives 1-3 is reported. Their electronic absorption
      spectra, in view of photoinduced intramolecular charge transfer, and their
      electrochemical behavior were investigated, and pK(a) values for the two
      protonation processes on the acceptor unit were determined in organic solvents by
      photometric titration. The influence of the TTF moiety on these values is
      discussed.

PMID- 19115306
TI  - Chemoselective capture of glycans for analysis on gold nanoparticles:
      carbohydrate oxime tautomers provide functional recognition by proteins.
AB  - Nanoparticles functionalized with glycans are emerging as powerful solid-phase
      chemical tools for the study of protein-carbohydrate interactions using nanoscale
      properties for detection of binding events. Methods or reagents that enable the
      assembly of glyconanoparticles from unprotected glycans in two consecutive
      chemoselective steps with meaningful display of the glycan are highly desirable.
      Here, we describe a novel bifunctional reagent that 1) couples to glycans by
      oxime formation in solution, 2) aids in purification through a lipophilic trityl
      tag, and 3) after deprotection then couples to gold nanoparticles through a
      thiol. NMR studies revealed that these oximes exist as both the open-chain and N
      glycosyl oxy-amine tautomers. Glycan-linker conjugates were coupled through
      displacement of ligands from preformed, citrate-stabilized gold nanoparticles.
      Recognition of these glycans by proteins was studied with a lectin, concanavalin
      A (ConA), in an aggregation assay and with a processing enzyme and glucoamylase
      (GA). We demonstrate that the presence of the N-glycosyl oxy-amines clearly
      enables functional recognition in sharp contrast to the corresponding reduced oxy
      amines. This concept is then realized in a novel reagent, which should facilitate
      nanoglycobiology by enabling the operationally simple capture of glycans and
      their biologically meaningful display.

PMID- 19115307
TI  - Magnetic interactions and magnetic anisotropy in exchange coupled 4f-3d systems:
      a case study of a heterodinuclear Ce3+-Fe3+ cyanide-bridged complex.
AB  - We report here a detailed single-crystal EPR and magnetic study of a homologous
      series of complexes of the type Ln-M (Ln = La(III), Ce(III); M = Fe(III),
      Co(III)). We were able to obtain a detailed picture of the low-lying levels of
      Ce(III) and Fe(III) centres through the combined use of single-crystal EPR and
      magnetic susceptibility data. We show that classical ligand field theory can be
      of great help in rationalising the energies of the low-lying levels of both the
      transition-metal and rare-earth ions. The combined analysis of single-crystal EPR
      and magnetic data of the coupled system Ce-Fe confirmed the great complexity of
      the interactions involving rare-earth elements. With little uncertainty, it
      turned out clearly that the description of the interaction involving the lowest
      lying spin levels requires the introduction of the isotropic, anisotropic and
      antisymmetric terms.

PMID- 19115308
TI  - Facile functionalization of multilayer fullerenes (carbon nano-onions) by nitrene
      chemistry and "grafting from" strategy.
AB  - Facile functionalization of multilayer fullerenes (carbon nano-onions, CNOs) was
      carried out by [2+1] cycloaddition of nitrenes. The products were further
      derivatized by using the "grafting from" strategy of in situ ring-opening
      polymerization (ROP) and atom transfer radical polymerization (ATRP). Using one
      step nitrene chemistry with high-energy reagents, such as azidoethanol and
      azidoethyl 2-bromo-2-methyl propanoate, in N-methyl-2-pyrrolidone at 160 degrees
      C for 16 h, hydroxyl and bromide functionalities were introduced onto the
      surfaces of CNOs. These hydroxyl CNOs (CNO-OH) and bromic CNOs (CNO-Br) were
      extensively characterized by various techniques such as thermal gravimetric
      analysis (TGA), transmission electron microscopy (TEM), Raman spectroscopy and X
      ray photo electron spectroscopy (XPS). TGA measurements indicated that the
      surface hydroxyl and bromide group density reached 1.49 and 0.49 mmol g(-1),
      respectively. The as-functionalized CNOs showed much better solubility in
      solvents than pristine CNOs. The CNO-OH were also observed to fluoresce at lambda
      = 453 nm in water. The CNO-OH and CNO-Br can be conveniently utilized as
      macroinitiators to conduct surface-initiated in-situ polymerizations.
      Poly(epsilon-caprolactone) (PCL, 45 wt%) and polystyrene (PS, 60 wt%) were then
      grafted from surfaces of CNOs through the ROP of epsilon-caprolactone with the
      macroinitiator CNO-OH and the ATRP of styrene with the macroinitiator CNO-Br,
      respectively. The structures and morphology of the resulting products were
      characterized by (1)H NMR, scanning electron microscopy (SEM), TEM, and atomic
      force microscopy (AFM). The polymer functionalized CNOs have good
      solubility/dispersibility in common organic solvents. The facile and scalable
      functionalization approaches can pave the way for the comprehensive investigation
      of chemistry of CNOs and fabrication of novel CNO-based nanomaterials and
      nanodevices.

PMID- 19115309
TI  - MALDI-TOF mass-spectrometry-based versatile method for the characterization of
      protein kinases.
AB  - We describe a MALDI-TOF mass-spectrometry-based method that is rapid and
      versatile for the characterization of protein kinases and their inhibitors. We
      have designed new kinase substrates by the modification of common synthetic
      peptides, such as kemptide (LRRALSG), CaMKII substrate (KRQQSFDLF), erktide
      (ATGPLSPGPFGRR), abltide (EAIYAAPFAKKK), srctide (AEEEIYGEFEAKKKK), neurogranin
      (AAAKIQASFRGHMARKK), and casein kinase I (CKI) substrate (RRKDLHDDEEDEAMSITA).
      There are two fundamental points on which the proposed method is based to improve
      the mass-spectrometric response: 1) mass tag technology by N-derivatization
      through stable isotope labeling and 2) C-terminal conjugation with
      tryptophanylarginine (WR). It was suggested that C-terminal conjugation with the
      WR moiety enhances the ionization potency of these new substrates 1.5-13.7 times
      as much as those of the original peptides. We demonstrated, by using modified
      abltide (Ac-EAIYAAPFAKKKWR-NH(2)), that WR conjugation at the C-terminus in
      combination with stable-isotope labeling at the N-terminus allowed the
      quantitative assay of recombinant c-Abl kinase in the presence of adenosine 5'
      triphosphate (ATP; K(M,ATP)=18.6 microM and V(max)=642 pmol min(-1) microg(-1)).
      The present protocol made a simple and reliable inhibition assay of recombinant c
      Abl kinase by imatinib possible (IC(50(recombinant))=291 nM; STI571, Gleevec;
      Novartis Pharma). Moreover, it was also demonstrated that this ATP noncompetitive
      inhibitor differentiates between two conformers of c-Abl kinases: the
      phosphorylated active and dephosphorylated inactive forms (IC(50(active
      form))=1049 nM and IC(50(inactive form))=54 nM). The merit of this approach is
      evident because the present protocol can be applied to the direct monitoring of
      the activities of living cell kinases by using cancer-cell lines, such as mouse
      B16 melanoma cells and human lung cancer K562 cells. A multiple-kinase assay that
      uses K562 cell lysate in the presence of seven new synthetic substrates made high
      throughput inhibitor profiling possible. It should be emphasized that this
      radioactive isotope-free quantitative kinase assay will greatly accelerate the
      discovery of a new generation of potential kinase inhibitors that exhibit highly
      selective or unique inhibitory profiles.

PMID- 19115310
TI  - Stereoselective hydrogenation of olefins using rhodium-substituted carbonic
      anhydrase--a new reductase.
AB  - One useful synthetic reaction missing from nature's toolbox is the direct
      hydrogenation of substrates using hydrogen. Instead nature uses cofactors like
      NADH to reduce organic substrates, which adds complexity and cost to these
      reductions. To create an enzyme that can directly reduce organic substrates with
      hydrogen, researchers have combined metal hydrogenation catalysts with proteins.
      One approach is an indirect link where a ligand is linked to a protein and the
      metal binds to the ligand. Another approach is direct linking of the metal to
      protein, but nonspecific binding of the metal limits this approach. Herein, we
      report a direct hydrogenation of olefins catalyzed by rhodium(I) bound to
      carbonic anhydrase (CA-[Rh]). We minimized nonspecific binding of rhodium by
      replacing histidine residues on the protein surface using site-directed
      mutagenesis or by chemically modifying the histidine residues. Hydrogenation
      catalyzed by CA-[Rh] is slightly slower than for uncomplexed rhodium(I), but the
      protein environment induces stereoselectivity favoring cis- over trans-stilbene
      by about 20:1. This enzyme is the first cofactor-independent reductase that
      reduces organic molecules using hydrogen. This catalyst is a good starting point
      to create variants with tailored reactivity and selectivity. This strategy to
      insert transition metals in the active site of metalloenzymes opens opportunities
      to a wider range of enzyme-catalyzed reactions.

PMID- 19115311
TI  - Osmotically shrunken LIPOCEST agents: an innovative class of magnetic resonance
      imaging contrast media based on chemical exchange saturation transfer.
AB  - The peculiar properties of osmotically shrunken liposomes acting as magnetic
      resonance imaging-chemical exchange saturation transfer (MRI-CEST) contrast
      agents have been investigated. Attention has been primarily devoted to assessing
      the contribution arising from encapsulated and incorporated paramagnetic
      lanthanide(III)-based shift reagents in determining the chemical shift of the
      intraliposomal water protons, which is a relevant factor for generating the CEST
      contrast. It is demonstrated that a highly shifted resonance for the encapsulated
      water can be attained by increasing the percentage of the amphiphilic shift
      reagent incorporated in the liposome bilayer. It is also demonstrated that the
      shift contribution arising from the bulk magnetic susceptibility can be optimized
      through the modulation of the osmotic shrinkage. In terms of sensitivity, it is
      shown that the saturation transfer efficiency can be significantly improved by
      increasing the size of the vesicle, thus allowing a high number of exchangeable
      protons to be saturated. In addition, the role played by the intensity of the
      saturating radiofrequency field has also been highlighted.

PMID- 19115312
TI  - Alkali metal oligoether carboxylates--a new class of ionic liquids.

PMID- 19115313
TI  - Using Biomonitoring Equivalents to interpret human biomonitoring data in a public
      health risk context.
AB  - Increasingly sensitive analytical tools allow measurement of trace concentrations
      of chemicals in human biological media in persons from the general population.
      Such data are being generated by biomonitoring programs conducted by the US
      Centers for Disease Control and other researchers. However, few screening tools
      are available for interpretation of such data in a health risk assessment
      context. This review describes the concept and implementation of Biomonitoring
      Equivalents (BEs), estimates of the concentration of a chemical or metabolite in
      a biological medium that is consistent with an existing exposure guidance value
      such as a tolerable daily intake or reference dose. The BE approach integrates
      available pharmacokinetic data to convert an existing exposure guidance value
      into an equivalent concentration in a biological medium. Key concepts regarding
      the derivation and communication of BE values resulting from an expert workshop
      held in 2007 are summarized. BE derivations for four case study chemicals
      (toluene, 2,4-dichlorophenoxyacetic acid, cadmium and acrylamide) are presented,
      and the interpretation of biomonitoring data for these chemicals is presented
      using the BE values. These case studies demonstrate that a range of
      pharmacokinetic data and approaches can be used to derive BE values; fully
      developed physiologically based pharmacokinetic models, while useful, are not
      required. The resulting screening level evaluation can be used to classify these
      compounds into relative categories of low, medium and high priority for risk
      assessment follow-up. Future challenges related to the derivation and use of BE
      values as tools in risk management are discussed.

PMID- 19115314
TI  - 5-Fluorouracil and its active metabolite FdUMP cause DNA damage in human SW620
      colon adenocarcinoma cell line.
AB  - 5-Fluorouracil (5-FU) is an antineoplasic drug widely used to treat cancer. Its
      cytotoxic effect has been principally ascribed to the misincorporation of
      fluoronucleotides into DNA and RNA during their synthesis, and the inhibition of
      thymidylate synthase (TS) by FdUMP (one of the 5-FU active metabolites), which
      leads to nucleotide pool imbalance. In the present study, we compared the ability
      of 5-FU and FdUMP to induce apoptosis and to influence the cell cycle progression
      in human colon SW620 adenocarcinoma cells in regards to their genotoxic and
      clastogenic activities. Our study demonstrates that 5-FU induces SSB, DSB and
      apoptosis earlier than FdUMP. Interestingly, while both drugs are able to induce
      apoptosis, their effect on the cell cycle progression differed. Indeed, 5-FU
      induces an arrest in G1/S while FdUMP causes an arrest in G2/M. Independently of
      the temporal difference in strand breaks and apoptosis induction, as well as the
      differential cell cycle modulation, both drugs presented similar clastogenic
      effects. The different pattern of cell cycle arrest suggests that the two drugs
      induce different types of primary DNA lesions that could lead to the activation
      of different checkpoints and recruit different DNA repair pathways.

PMID- 19115315
TI  - The interaction of KCTD1 with transcription factor AP-2alpha inhibits its
      transactivation.
AB  - AP-2 is a transcription factor implicated in mammalian development, cell
      proliferation, apoptosis, and carcinogenesis. To identify potential AP-2alpha
      interacting partners, a yeast two-hybrid screen was performed in human brain cDNA
      library. One of the identified clones encodes potassium channel tetramerization
      domain-containing 1 (KCTD1). We demonstrated the novel KCTD1-AP-2alpha
      interaction in vitro by GST pull-down assays and in vivo by co
      immunoprecipitation assays and mapped the interaction domains to the N-termini of
      both proteins. In addition, we observed that the two proteins were completely co
      localized in the nuclei of mammalian cells. Transient transfection assays using
      four promoters containing AP-2-binding sites confirmed that KCTD1 significantly
      repressed AP-2alpha-mediated transactivation through the BTB domain, whereas
      KCTD1 siRNA strongly relieved KCTD1-mediated repression of AP-2alpha
      transcriptional activity, and other BTB domain proteins such as PDIP1, KCTD10,
      and TNFAIP1 did not markedly inhibit the transcriptional activity of AP-2alpha,
      suggesting that KCTD1 specifically acts as a negative regulator of AP-2alpha.
      Finally, we found that KCTD1 interacted with three major members of the AP-2
      family and inhibited their transcriptional activities. Taken together, our
      results indicate the novel function of KCTD1 as the transcriptional repressor for
      AP-2 family, especially for AP-2alpha.

PMID- 19115316
TI  - VSL#3 probiotic treatment attenuates fibrosis without changes in steatohepatitis
      in a diet-induced nonalcoholic steatohepatitis model in mice.
AB  - Nonalcoholic fatty liver disease (NAFLD) and its advanced stage, nonalcoholic
      steatohepatitis (NASH), are the most common causes of chronic liver disease in
      the United States. NASH features the metabolic syndrome, inflammation, and
      fibrosis. Probiotics exhibit immunoregulatory and anti-inflammatory activity. We
      tested the hypothesis that probiotic VSL#3 may ameliorate the methionine-choline
      deficient (MCD) diet-induced mouse model of NASH. MCD diet resulted in NASH in
      C57BL/6 mice compared to methionine-choline-supplemented (MCS) diet feeding
      evidenced by liver steatosis, increased triglycerides, inflammatory cell
      accumulation, increased tumor necrosis factor alpha levels, and fibrosis. VSL#3
      failed to prevent MCD-induced liver steatosis or inflammation. MCD diet, even in
      the presence of VSL#3, induced up-regulation of serum endotoxin and expression of
      the Toll-like receptor 4 signaling components, including CD14 and MD2, MyD88
      adaptor, and nuclear factor kappaB activation. In contrast, VSL#3 treatment
      ameliorated MCD diet-induced liver fibrosis resulting in diminished accumulation
      of collagen and alpha-smooth muscle actin. We identified increased expression of
      liver peroxisome proliferator-activated receptors and decreased expression of
      procollagen and matrix metalloproteinases in mice fed MCD+VSL#3 compared to MCD
      diet alone. MCD diet triggered up-regulation of transforming growth factor beta
      (TGFbeta), a known profibrotic agent. In the presence of VSL#3, the MCD diet
      induced expression of TGFbeta was maintained; however, the expression of Bambi, a
      TGFbeta pseudoreceptor with negative regulatory function, was increased. In
      summary, our data indicate that VSL#3 modulates liver fibrosis but does not
      protect from inflammation and steatosis in NASH. The mechanisms of VSL#3-mediated
      protection from MCD diet-induced liver fibrosis likely include modulation of
      collagen expression and impaired TGFbeta signaling.

PMID- 19115321
TI  - Triple-resonance coherent anti-stokes Raman scattering microspectroscopy.
AB  - Fluorescence-free microscopy: A new nonlinear optical microspectroscopy
      technique, femtosecond (fs) triple-resonance coherent anti-Stokes Raman
      scattering, in which the amplitude and phase of input fs laser pulses are
      optimally shaped to be in triple resonance with the molecular electronic and
      vibrational transitions, generates a coherent nonlinear signal beam at a new
      color with a highest possible efficiency (see figure).

PMID- 19115320
TI  - Identification, quantification, and determination of the absolute configuration
      of the bacterial quorum-sensing signal autoinducer-2 by gas chromatography-mass
      spectrometry.
AB  - SENSING THE SIGNAL: A gas chromatography-mass spectrometry (GC-MS) method for the
      analysis of the quorum-sensing autoinducer-2 is described. It allows, for the
      first time, the direct analysis and accurate determination of this highly water
      soluble signaling compound, which exists in complex equilibria. The application
      on the caries-causing bacterium Streptococcus mutans is described. Autoinducer-2
      (AI-2) is an important, small extracellular signaling molecule that is used by
      many bacteria. It is part of the AI-2 pool, a group of equilibrium-connected
      compounds derived from (S)-4,5-dihydroxy-2,3-pentanedione [(S)-DPD, 1].
      Currently, these compounds are analyzed by indirect methods relying on the
      luminescence of sensor strains, the fluorescence of receptor proteins modified
      with fluorophores, or by isolation procedures not practical for quantitative
      analysis. Herein, we report a direct analytical procedure that allows for the
      unambiguous identification and quantification of molecular species by mass
      spectrometry. Phenylenediamine reacts readily and quantitatively with 1 to form
      the quinoxalinediol 12 under aqueous conditions. The extraction and silylation of
      this compound results in the formation of a silyl ether (13), which is amenable
      for analysis by gas chromatography-mass spectrometry. The use of an isotopically
      labeled variant (16) of 12 as an internal standard opens the possibility for the
      accurate quantification of samples containing AI-2 or its equilibrium products.
      The analysis of cell-free culture supernatants of Vibrio harveyi and
      Streptococcus mutans allowed for the accurate quantification of the AI-2
      concentration above the limit of detection (0.7 ng mL(-1)). No compounds were
      detected in mutants lacking the capability to produce AI-2. In addition, the
      absolute configuration of 1 can be analyzed using the derivative 13 by chiral gas
      chromatography.

PMID- 19115322
TI  - Reconfigurable logic devices on a single dopant atom - operation up to a full
      adder by using electrical spectroscopy.
AB  - A silicon field-effect transistor is operated as a logic circuit by electrically
      addressing the ground and excited electronic states of an embedded single dopant
      atom. Experimental results-complemented by analytical and computational
      calculations-are presented. First, we show how a complete set of binary logic
      gates can be realized on the same hardware. Then, we show that these gates can be
      operated in parallel on the very same dopant up to the logic level of a full
      adder. To use the device not as a switch but as a full logic circuit, we make
      essential use of the excited electronic states of the dopant and of the ability
      to shift their energy by gating. The experimental ability to use two channels to
      measure the current flowing through the device and the conductance (dI/dV) allows
      for a robust reading of the output of the logic operations.

PMID- 19115323
TI  - Electron transport through conjugated molecules: when the pi system only tells
      part of the story.
AB  - In molecular transport junctions, current is monitored as a function of the
      applied voltage for a single molecule assembled between two leads. The transport
      is modulated by the electronic states of the molecule. For the prototypical
      delocalized systems, namely, pi-conjugated aromatics, the pi system usually
      dominates the transport. Herein, we investigate situations where model
      calculations including only the pi system do not capture all of the subtleties of
      the transport properties. Including both the sigma and pi contributions to charge
      transport allows us to demonstrate that while there is generally good agreement,
      there are discrepancies between the methods. We find that model calculations with
      only the pi system are insufficient where the transport is dominated by quantum
      interference and cases where geometric changes modulate the coupling between
      different regions of the pi system. We examine two specific molecular test cases
      to model these geometric changes: the angle dependence of coupling in (firstly) a
      biphenyl and (secondly) a nitro substituent of a cross-conjugated unit.

PMID- 19115324
TI  - Band-gap modification in a nanoscale region of polyethylene by fast electrons.
AB  - Drastic change: A nanoscale spot of polyethylene (PE) can change its electrical
      properties dramatically after exposure to fast electrons-from a representative
      insulator, via a semiconductor, to a hopping conductor (see picture). These
      modifications of the chemical and energy-band structures of PE are extremely
      localized, thus opening a new way to use this conventional polymer in
      nanotechnology. Herein, a nanoscale area on a polyethylene film is investigated
      by an electron-microscope-electron-spectroscopy system after exposure to various
      doses of fast electrons. Therefore, modifications in its physical and chemical
      properties and the spatial size of a beam-affected area are measured. The results
      show that the modifications of PE by electrons are significant enough to rebuild
      the chemical and energy-band structures. Hydrogen is removed through scission
      while pi bonds are formed by cross-linking between main chains. These changes
      cause the energy band of PE to show dramatic variation from a wide to a narrow
      (down to approximately 0.8 eV) band-gap. At the highest dose (10(10) C m(-2))
      used herein, an illuminated area of PE becomes quite similar in properties to
      graphitic amorphous carbon. On the other hand, the size of the beam-affected area
      is as small as roughly 50 nm in diameter. Since the extent of the modifications
      can be tailored in a controllable way by the dose, these findings may be
      fundamental for the utilization of a conventional polymer in nanotechnology.

PMID- 19115325
TI  - Progress in mimetic studies of cell adhesion and the mechanosensing.
AB  - Vesicle-substrate adhesion has been studied for over two decades with the
      motivation to understand and mimic cell adhesion. In recent years, with progress
      in theoretical modelling, the development of experimental techniques, and
      improved data-analysis procedures, considerable advances have been made in the
      understanding of the adhesion process. It is this progress which constitutes the
      focus of this review.

PMID- 19115326
TI  - The influence of charge transport and recombination on the performance of dye
      sensitized solar cells.
AB  - Electrochemical impedance spectroscopy (EIS) and transient voltage decay
      measurements are applied to compare the performance of dye sensitized solar cells
      (DSCs) using organic electrolytes, ionic liquids and organic-hole conductors as
      hole transport materials (HTM). Nano-crystalline titania films sensitized by the
      same heteroleptic ruthenium complex NaRu(4-carboxylic acid-4'-carboxylate) (4,4'
      dinonyl-2,2'-bipyridyl)(NCS)(2) , coded Z-907Na are employed as working
      electrodes. The influence of the nature of the HTM on the photovoltaic figures of
      merit, that is, the open circuit voltage, short circuit photocurrent and fill
      factor is evaluated. In order to derive the electron lifetime, as well as the
      electron diffusion coefficient and charge collection efficiency, EIS measurements
      are performed in the dark and under illumination corresponding to realistic
      photovoltaic operating conditions of these mesoscopic solar cells. A theoretical
      model is established to interpret the frequency response off the impedance under
      open circuit conditions, which is conceptually similar to photovoltage transient
      decay measurements. Important information on factors that govern the dynamics of
      electron transport within the nanocrystalline TiO(2) film and charge
      recombination across the dye sensitized heterojunction is obtained.

PMID- 19115327
TI  - Scaled MP3 non-covalent interaction energies agree closely with accurate CCSD(T)
      benchmark data.
AB  - Scaled MP3 interaction energies calculated as a sum of MP2/CBS (complete basis
      set limit) interaction energies and scaled third-order energy contributions
      obtained in small or medium size basis sets agree very closely with the estimated
      CCSD(T)/CBS interaction energies for the 22 H-bonded, dispersion-controlled and
      mixed non-covalent complexes from the S22 data set. Performance of this so-called
      MP2.5 (third-order scaling factor of 0.5) method has also been tested for 33
      nucleic acid base pairs and two stacked conformers of porphine dimer. In all the
      test cases, performance of the MP2.5 method was shown to be superior to the
      scaled spin-component MP2 based methods, e.g. SCS-MP2, SCSN-MP2 and SCS(MI)-MP2.
      In particular, a very balanced treatment of hydrogen-bonded compared to stacked
      complexes is achieved with MP2.5. The main advantage of the approach is that it
      employs only a single empirical parameter and is thus biased by two rigorously
      defined, asymptotically correct ab-initio methods, MP2 and MP3. The method is
      proposed as an accurate but computationally feasible alternative to CCSD(T) for
      the computation of the properties of various kinds of non-covalently bound
      systems.

PMID- 19115328
TI  - Identification of physiological and toxic conformations in Abeta42 aggregates.
AB  - Aggregation of the 42-residue amyloid beta-protein (Abeta42) plays a crucial role
      in the pathogenesis of Alzheimer's disease (AD). Despite numerous structural
      studies on Abeta aggregates, the relationship between tertiary structure and
      toxicity remains unclear. Our proline scanning and solid-state NMR studies
      suggested that aggregates both of wild-type Abeta42 and of E22K-Abeta42 (one of
      the mutants related to cerebral amyloid angiopathy) contain two conformers: a
      major one with a turn at positions 25 and 26, and a minor one with a turn at
      positions 22 and 23. To identify the toxic conformer, the derivative Abeta42
      lactam(22K-23E), in which the side chains at positions 22 and 23 were covalently
      linked, was synthesized as a minor conformer surrogate, along with Abeta42
      lactam(25K-26E) as a major conformer surrogate. The Abeta42-lactam(22K-23E)
      showed stronger aggregation, neurotoxicity, radical generation, and
      oligomerization than wild-type Abeta42, whereas in Abeta42-lactam(25K-26E) were
      weak. The transition from the physiological conformation with a turn at positions
      25 and 26 to the toxic conformation with a turn at positions 22 and 23 might be a
      key event in the pathogenesis of AD.

PMID- 19115329
TI  - Enhanced cellular uptake and cytotoxicity studies of organometallic bioconjugates
      of the NLS peptide in Hep G2 cells.
AB  - SPACE INVADERS: Organometallic fragments such as the ferrocenyl group (shown in
      red in the picture) help to enhance cellular entry of NLS peptides. Eventually,
      these nontoxic conjugates find their way to the cellular nucleus as shown by
      fluorescence microscopy studies in this work. Intracellular delivery to
      biomolecular targets is still a major challenge in molecular and cell biology. We
      recently found that attaching an organometallic group, namely the cobaltocenium
      cation, to the SV 40 large T antigen nuclear localisation signal (NLS) greatly
      enhances cellular uptake of the conjugate (Noor et al., Angew. Chem. Int. Ed.
      2005, 45, 2429). In addition, nuclear localisation of the conjugate was observed.
      In this work, we present a thorough investigation of this novel cellular delivery
      system with respect to the nature of the metal complex and the peptide sequence.
      A number of ferrocene ((Fe(II)), neutral metal complex) and cobaltocenium
      ((Co(III)), cationic metal complex) bioconjugates with both the NLS wild-type
      sequence PKKKRKV and a scrambled sequence (NLS(scr), KKVKPKR) were prepared by
      solid-phase peptide synthesis (SPPS). Cellular and nuclear uptake of these
      bioconjugates was studied by fluorescence microscopy on living Hep G2 cells. In
      addition, cytotoxicity screening on the conjugates was carried out, as the toxic
      effects of several simple metallocenes have been noted previously. Rapid cellular
      uptake as well as nuclear localisation was observed for the metal-NLS conjugates,
      but not for any dipeptide controls, the metal-NLS(scr) conjugates or any metal
      free conjugates. It thus appears that the presence of a metallocene, but not its
      charge, and the correct NLS sequence is essential for cellular uptake.
      Fluorescence microscopy co-localisation studies did not reveal a significant
      endosomal entrapment of the conjugates. The metallocene not only provides a
      hydrophobic handle for membrane translocation but also facilitates the
      localisation and distribution of the conjugate in the cytoplasm. The NLS peptide
      on the other hand is responsible for the nuclear localisation of the
      bioconjugate. Finally, none of the conjugates were found to be toxic up to the
      highest concentrations that was tested (1 mM) against the Hep G2 cells that were
      used in this study. In conclusion, this work supports metallocene-NLS
      bioconjugates, in particular with the very robust cobaltocenium group, as a
      simple but potent, nontoxic system for cellular uptake and nuclear delivery.
      Concurrently, our finding is relevant to the still-unresolved question of
      cytotoxicity of metallocenes because it excludes binding and/or damage to the DNA
      as a mechanism of metallocene cytotoxicity. This finding is confirmed by a
      combined yeast cytotoxicity/genotoxicity assay, which also shows very little
      toxic effects for all organometal-NLS conjugates that were tested.

PMID- 19115330
TI  - Shaping the polypropionate biosynthesis in the solar-powered mollusc Elysia
      viridis.
AB  - Polypropionates that incorporate pyrones are a family of polyketides featuring
      the chemistry of a few marine molluscs capable of phototrophic CO(2) fixation as
      a result of storing viable symbiotic chloroplasts in their bodies. The role and
      origin of these molecules is poorly investigated, although the unusual biological
      activities and chemistry of these natural products have recently received renewed
      interest. Here, we report the results of in vivo studies on production of gamma
      pyrone-containing polypropionates in the Mediterranean mollusc Elysia viridis.
      Biosynthesis of the metabolites in the sacoglossan is shown to proceed through
      condensation of eight intact C(3) units by polyketide synthase assembly. LC-MS
      and NMR spectroscopic studies demonstrate that the process involves a pyrone
      tetraene (10) as key intermediate, whereas the levels of the final
      polypropionates (6, 7 and 9) are related to each other and show a significant
      dependence upon light conditions.

PMID- 19115331
TI  - Influence of calcitonin administration on ultimobranchial and parathyroid glands
      of pigeon, Columba livia.
AB  - Pigeons were divided into two numerically equal groups (A and B) containing 30
      specimens each. Birds from group A were intraperitoneally injected daily with 0.1
      mL/100 g body wt of vehicle (0.1 M acetate buffer, pH 4.3 containing 0.1%
      gelatin). Specimens from group B were intraperitoneally injected daily with 1
      microg/100 g body wt of salmon calcitonin. Six birds were sacrificed from each
      group 2 h after the last injection on 1st, 3rd, 5th, 10th, and 15th day of the
      experiment. After collection of blood samples, ultimobranchial and parathyroid
      glands were fixed for histological studies. In calcitonin-treated C. livia, the
      plasma calcium levels exhibit a progressive decline from day 1 till day 5. On day
      15, the levels become more or less similar to the control value. No change has
      been noticed on day 1 in the plasma phosphate levels of calcitonin-treated C.
      livia. The levels decrease progressively from day 3 to day 5; thereafter, it
      exhibits an elevation so that on day 15, normal plasma phosphate levels is
      achieved. The ultimobranchial gland of C. livia exhibits no change up to day 5
      following calcitonin treatment. The nuclear volume of ultimobranchial cells
      exhibits a decrease on day 10. This response progresses up to day 15. Few
      degenerating cells are also discerned following 15 days calcitonin treatment. The
      parathyroid gland of calcitonin-treated C. livia exhibits no histological
      alteration up to day 3. The nuclear volume of parathyroidal cells exhibits a
      progressive increase from day 3 till the close of the experiment (day 15).
      Moreover, the gland exhibits more compactness on day 10 and day 15. Few
      degenerating cells are encountered after day 15 following calcitonin treatment.

PMID- 19115332
TI  - Recognition, presence, and survival of locust central nervous glia in situ and in
      vitro.
AB  - Insect glial cells serve functions for the formation, maintenance, and
      performance of the central nervous system in ways similar to their vertebrate
      counterparts. Characterization of physiological mechanisms that underlie the
      roles of glia in invertebrates is largely incomplete, partly due to the lack of
      markers that universally label all types of glia throughout all developmental
      stages in various species. Studies on primary cell cultures from brains of
      Locusta migratoria demonstrated that the absence of anti-HRP immunoreactivity,
      which has previously been used to identify glial cells in undissociated brains,
      can also serve as a reliable glial marker in vitro, but only in combination with
      a viability test. As cytoplasmic membranes of cultured cells are prone to
      degradation when they lose viability, only cells that are both anti-HRP
      immunonegative and viable should be regarded as glial cells, whereas the lack of
      anti-HRP immunoreactivity alone is not sufficient. Cell viability can be assessed
      by the pattern of nuclear staining with DAPI (4',6-diamidino-2-phenylindole), a
      convenient, sensitive labeling method that can be used in combination with other
      immunocytochemical cellular markers. We determined the glia-to-neuron ratio in
      central brains of fourth nymphal stage of Locusta migratoria to be 1:2 both in
      situ and in dissociated primary cell cultures. Analysis of primary cell cultures
      revealed a progressive reduction of glial cells and indicated that dead cells
      detach from the substrate and vanish from the analysis. Such changes in the
      composition of cell cultures should be considered in future physiological studies
      on cell cultures from insect nervous systems.

PMID- 19115333
TI  - Human beta-defensin-3 promotes wound healing in infected diabetic wounds.
AB  - BACKGROUND: Infected wounds present a major complication in patients with
      diabetes. Staphylococcus aureus is the most common single isolate in diabetic
      wounds. Human beta-defensin (hBD)-3 is antimicrobial active and appears to play a
      key role in the immune response. The present study aimed to analyse the effect of
      hBD-3 expression in a model of infected diabetic wounds. METHODS: Excisional
      wounds were created on the backs of Yorkshire pigs and Ad5-CMV-hBD-3 vectors were
      microseeded. Wounds were inoculated with S. aureus, covered with a polyurethane
      chamber and analysed for transgene expression, bacterial infection, re
      epithelialization, wound contraction, wound fluid production and blood vessel
      formation. RESULTS: hBD-3-treated wounds showed a total bacterial load of 2.1 x
      10(8) colony-forming units (CFU)/g tissue, versus 1.3 x 10(9) CFU/g tissue for
      controls (p < 0.001) at day 4. At day 12, no statistical difference could be
      detected. Re-epithelialization showed 75 +/- 15% wound closure for hBD-3
      expressing wounds and 50 +/- 16% for controls (p < 0.01). hBD-3 expression was in
      the range 15-20 ng/ml of wound fluid during day 1-4. The lower dose of 2 x 10(9)
      Ad5-CMV-hBD-3 showed no effect, suggesting a dose dependency for hBD-3.
      CONCLUSIONS: In the present study, we show that hBD-3 expression significantly
      promotes wound closure in S. aureus infected diabetic wounds in a preclinical
      large-animal model. Furthermore, a ten-fold reduction of bacterial growth on day
      4 was detected. These findings indicate that beta-defensin-3 may play a major
      role in diabetic wound healing and wound infections.

PMID- 19115334
TI  - Ex uno plures ("out of one, many"): new paradigms for expanding the range of
      polyolefins through reversible group transfers.
AB  - The "mature" status presently enjoyed by polyolefins prepared with homogeneous
      (soluble) single-site catalysts through the transition-metal-catalyzed
      coordination polymerization of ethene and 1-alkenes brings with it a common
      impression that it is now routinely possible to obtain, with a high degree of
      confidence, any desired stereochemical microstructure or copolymer composition
      through iterative optimization employing a set of mutationally related synthetic
      derivatives generated from an initial molecular design. The dominant reliance on
      this "one catalyst, one material" strategic approach to discovery is
      intrinsically self-limiting, however, owing to the limited pool of molecular
      structures that can be reasonably synthesized and drawn upon. Recently, non-chain
      terminating, reversible group-transfer processes have been purposefully
      introduced to olefin coordination polymerization. These processes, which are
      highly competitive with propagation, can be controlled externally and now provide
      the basis for new "one catalyst, many materials" paradigms that have the
      potential to greatly expand the reach of polyolefin materials for the 21st
      century.

PMID- 19115335
TI  - Modulation of the biological properties of aspirin by formation of a
      bioorganometallic derivative.

PMID- 19115336
TI  - Multivalent choline dendrimers as potent inhibitors of pneumococcal cell-wall
      hydrolysis.

PMID- 19115337
TI  - Size-selective helical stacking and template polymerization of oligosaccharides
      around a linear polymeric guest molecule.

PMID- 19115338
TI  - Highly active dizinc catalyst for the copolymerization of carbon dioxide and
      cyclohexene oxide at one atmosphere pressure.

PMID- 19115339
TI  - Versatile biocompatible polymer hydrogels: scaffolds for cell growth.

PMID- 19115340
TI  - Structure determination and total synthesis of bottromycin A2: a potent
      antibiotic against MRSA and VRE.

PMID- 19115341
TI  - Total syntheses of cytotoxic, naturally occurring kalasinamide, geovanine, and
      marcanine A.

PMID- 19115342
TI  - A copper-catalyzed tandem synthesis of indolo- and pyrrolo[2,1-a]isoquinolines.

PMID- 19115344
TI  - Copper-catalyzed asymmetric Michael addition of magnesium, zinc, and aluminum
      organometallic reagents: efficient synthesis of chiral molecules.

PMID- 19115343
TI  - Magnetically guided titania nanotubes for site-selective photocatalysis and drug
      release.

PMID- 19115345
TI  - Generation and validation of mice carrying a conditional allele of the epidermal
      growth factor receptor.
AB  - The epidermal growth factor receptor (EGFR) is important for normal homeostasis
      in a variety of tissues and, when abnormally expressed or mutated, contributes to
      the development of many diseases. However, in vivo functional studies are
      hindered by the lack of adult mice lacking EGFR because of the pre- and postnatal
      lethality of EGFR deficient mice. We generated a conditional allele of Egfr
      (Egfr(tm1Dwt)) by flanking exon 3 with loxP sites in order to investigate tissue
      specific functions of this widely expressed receptor tyrosine kinase. The
      activity of the Egfr(tm1Dwt) allele is indistinguishable from wildtype Egfr.
      Conversely, the Egfr(Delta) allele, generated by Cre-mediated deletion of exon 3
      using the germline EIIa-Cre transgenic line, functions as a null allele.
      Egfr(Delta/Delta) embryos that have complete ablation of EGFR activity and die at
      mid-gestation with placental defects identical to those reported for mice
      homozygous for the Egfr(tm1Mag) null allele. We also inactivated the Egfr(tm1Dwt)
      allele tissue-specifically in the skin epithelium using the K14-Cre transgenic
      line. These mice were viable but exhibited wavy coat hair remarkably similar to
      mice homozygous for the Egfr(wa2) hypomorphic allele or heterozygous for the
      Egfr(Wa5) antimorphic allele. These results suggest that the hairless phenotype
      of Egfr nullizygous mice is not solely due to absence of EGFR in the epithelium,
      but that EGFR activity is required also in skin stromal cells for normal hair
      morphogenesis. This new mouse model should have wide utility to inactivate Egfr
      conditionally for functional analysis of EGFR in adult tissues and disease
      states.

PMID- 19115347
TI  - Reactions of tin(II) hydride species with unsaturated molecules.

PMID- 19115346
TI  - Aggregated P19 mouse embryonal carcinoma cells as a simple in vitro model to
      study the molecular regulations of mesoderm formation and axial elongation
      morphogenesis.
AB  - Because of their capacity to give rise to various types of cells in vitro,
      embryonic stem and embryonal carcinoma (EC) cells have been used as convenient
      models to study the mechanisms of cell differentiation in mammalian embryos. In
      this study, we explored the mouse P19 EC cell line as an effective tool to
      investigate the factors that may play essential roles in mesoderm formation and
      axial elongation morphogenesis. We first demonstrated that aggregated P19 cells
      not only exhibited gene expression patterns characteristic of mesoderm formation
      but also displayed elongation morphogenesis with a distinct anterior-posterior
      body axis as in the embryo. We then showed by RNA interference that these
      processes were controlled by various regulators of Wnt signaling pathways, namely
      beta-catenin, Wnt3, Wnt3a, and Wnt5a, in a manner similar to normal embryo
      development. We further showed by inhibitor treatments that the axial elongation
      morphogenesis was dependent on the activity of Rho-associated kinase. Because of
      the convenience of these experimental manipulations, we propose that P19 cells
      can be used as a simple and efficient screening tool to assess the potential
      functions of specific molecules in mesoderm formation and axial elongation
      morphogenesis.

PMID- 19115348
TI  - Gecko-inspired directional and controllable adhesion.

PMID- 19115349
TI  - Dynamic combinatorial evolution within self-replicating supramolecular
      assemblies.

PMID- 19115350
TI  - Discrete self-assembly of iron(III) ions inside triple-stranded artificial DNA.

PMID- 19115351
TI  - A light-resistant organic sensitizer for solar-cell applications.
AB  - Finely tuned: A stable dye-sensitized solar cell that contains a molecularly
      engineered organic dye has been prepared. The efficiency of the cell remains at
      90% after 1000 h of light soaking at 60 degrees C. The remarkable stability of
      the cell is also reflected in the open-circuit voltage value (V(oc)), short
      circuit photocurrent-density value (J(sc)), and the fill factor, which also show
      barely no decline (see picture).

PMID- 19115352
TI  - MicroRNAs repress mainly through mRNA decay.

PMID- 19115353
TI  - Layer-by-layer electropeeling of organic conducting material imaged in real time.
AB  - Soft materials comprising low-molecular-weight organic molecules are attracting
      increasing interest because of their importance in the development of a number of
      emerging areas in nanoscience and technology, including molecular electronics,
      nanosystems for energy conversion, and devices in the widest sense. Their
      interaction with electrodes and their behavior under electric fields is a topic
      of vital significance for these areas, and about which very little is known. Here
      unprecedented evidence is presented for the controlled peeling of organic
      molecular material when a voltage is applied between the conducting system and
      the conducting probe of a scanning force microscope. The rate of removal of the
      material from the surface of the bulk conducting supramolecular material can be
      tuned. It depends on the potential applied and is initiated only above a
      threshold value of 200 mV. The results indicate the importance of electric fields
      on the stability and performance of conducting organic systems at the nanoscale.

PMID- 19115354
TI  - Stereocontrolled synthesis of beta-amino alcohols from lithiated aziridines and
      boronic esters.

PMID- 19115355
TI  - Controlled deposition of silver nanoparticles in mesoporous single- or multilayer
      thin films: from tuned pore filling to selective spatial location of nanometric
      objects.
AB  - Silver nanoparticle assemblies are embedded within mesoporous oxide thin films by
      an in situ mild reduction leading to nanoparticle-mesoporous oxide thin-film
      composites (NP@MOTF). A quantitative method based on X-ray reflectivity is
      developed and validated with energy dispersive spectroscopy in order to assess
      pore filling. The use of dilute formaldehyde solutions leads to control over the
      formation of silver nanoparticles within mesoporous titania films. Inclusion of
      silver nanoparticles in mesoporous silica requires more drastic conditions. This
      difference in reactivity can be exploited to selectively synthesize nanoparticles
      in a predetermined layer of a multilayered mesoporous stack leading to complex 1D
      ordered multilayers with precise spatial location of nanometric objects. The
      metal oxide nanocomposites synthesized have potential applications in catalysis,
      optical devices, surface-enhanced Raman scattering, and metal enhancement
      fluorescence.

PMID- 19115356
TI  - Synthetic lectins.
AB  - Improving on Mother Nature? The carbohydrate recognition demonstrated by
      supramolecular systems in water can now compete with that of natural systems,
      both in terms of affinity and selectivity. A synthetic carbohydrate receptor
      displays similar affinity for N-acetyl-D-glucosamine derivatives as the lectin
      wheat germ agglutinin and even greater selectivity (see picture: gray C, white H,
      blue N, red O).

PMID- 19115357
TI  - Adducts of NH3 with the conformers of glycidol: a rotational spectroscopy study.

PMID- 19115359
TI  - Regional differences in craniofacial diversity and the population history of
      Jomon Japan.
AB  - The people associated with the Jomon culture, the Neolithic inhabitants of Japan,
      are one of the key groups in the population history of East Asia, because they
      retain many archaic characters that may be traced back to Eurasian Upper
      Palaeolithic hunter-gatherers. In this study, the regional diversity of the Jomon
      skeletal series was estimated by applying the R-matrix method to 34 craniofacial
      measurements. The patterns of intraregional variation indicate little effect on
      the genetic structure of the Jomon from long-term gene flow stemming from an
      outside source. The regional diversities were further estimated by pooling all
      individuals into regional aggregates, and by computing the mean variance within
      local groups in each region. Although the pattern of phenotypic variation differs
      depending on the unit of analysis, the gradient of the diversity retains its
      identity. The Hokkaido region, the northernmost part of the Japanese archipelago,
      has the highest variance, followed by the regions of eastern Japan, while the
      southwestern regions have the lowest variance. These findings suggest that the
      Jomon ancestors of the northern part of Japan might have expanded southward to
      Honshu Island. Global analyses including samples from Eurasia, Africa, and
      Australia dating roughly to the same chronological periods as those of the Jomon
      samples, indicate that the Jomon cranial series share part of their ancestral
      gene pool with early northeastern Asians. The present findings support the
      archeologically suggested population growth and expansion in the northern half of
      the Eurasian continent during the late Pleistocene and early Holocene periods.

PMID- 19115358
TI  - Cycloaddition-promoted self-assembly of a polymer into well-defined beta sheets
      and hierarchical nanofibrils.

PMID- 19115360
TI  - Development of an anatomically based whole-body musculoskeletal model of the
      Japanese macaque (Macaca fuscata).
AB  - We constructed a three-dimensional whole-body musculoskeletal model of the
      Japanese macaque (Macaca fuscata) based on computed tomography and dissection of
      a cadaver. The skeleton was modeled as a chain of 20 bone segments connected by
      joints. Joint centers and rotational axes were estimated by joint morphology
      based on joint surface approximation using a quadric function. The path of each
      muscle was defined by a line segment connecting origin to insertion through an
      intermediary point if necessary. Mass and fascicle length of each were
      systematically recorded to calculate physiological cross-sectional area to
      estimate the capacity of each muscle to generate force. Using this anatomically
      accurate model, muscle moment arms and force vectors generated by individual limb
      muscles at the foot and hand were calculated to computationally predict muscle
      functions. Furthermore, three-dimensional whole-body musculoskeletal kinematics
      of the Japanese macaque was reconstructed from ordinary video sequences based on
      this model and a model-based matching technique. The results showed that the
      proposed model can successfully reconstruct and visualize anatomically
      reasonable, natural musculoskeletal motion of the Japanese macaque during
      quadrupedal/bipedal locomotion, demonstrating the validity and efficacy of the
      constructed musculoskeletal model. The present biologically relevant model may
      serve as a useful tool for comprehensive understanding of the design principles
      of the musculoskeletal system and the control mechanisms for locomotion in the
      Japanese macaque and other primates.

PMID- 19115362
TI  - Binge drinking in women at risk for developing eating disorders.
AB  - OBJECTIVE: To determine binge drinking rates in college-age women at risk for
      eating disorders and to examine factors related to binge drinking over time.
      METHOD: Participants were 480 college-age women who were at high risk for
      developing an eating disorder (ED) and who had a body mass index (BMI) between 18
      and 32. Participants were assessed annually for 4 years. RESULTS: Participants
      reported high rates of binge drinking and frequent binge drinking throughout
      college. Binge drinking was positively correlated with dietary restraint, coping
      using substances, coping using denial, and life events. DISCUSSION: The study's
      findings suggest that binge drinking is highly prevalent in women at high risk
      for developing eating disorders. Results also indicated that binge drinking was
      related to dieting and maladaptive coping patterns. Intervention for women with
      strong weight and shape concerns should also address problematic alcohol use.

PMID- 19115363
TI  - Inappropriate eating behaviors during pregnancy: prevalence and associated
      factors among pregnant women attending primary care in southern Brazil.
AB  - OBJECTIVE: To examine the prevalence of inappropriate eating behaviors and
      associated factors among pregnant women in primary care. METHOD: The Eating
      Disorder Examination Questionnaire was used to assess eating disorders and the
      Primary Care Evaluation of Mental Disorders was used to examine anxiety and
      depressive symptoms. Body mass index (BMI) and pregestational weight were also
      assessed. RESULTS: Prevalence of binge eating during pregnancy was 17.3% [95%
      confidence interval (CI) 14.5-20.0], followed by excessive shape (5.6%; 95% CI 4
      8) and weight concerns (5.5%; 95% CI 4-8). Binge eating during pregnancy was
      significantly associated with binge eating before pregnancy [prevalence ratio
      (PR) = 3.1; 95% CI 2.2-4.3], current anxiety symptoms (PR = 1.8; 95% CI 1.3-2.4),
      and prepregnancy BMI < 19.8 kg/m(2) (PR = 1.6; 95% CI 1.1-2.5). The prevalence of
      eating disorders was 0.6% (95% CI 0.01-1.11). DISCUSSION: Eating disorder
      symptoms should be routinely assessed and treated during prenatal care, along
      with other comorbid psychiatric symptoms such as anxiety.

PMID- 19115364
TI  - Anorexia nervosa: beyond boundaries.
AB  - OBJECTIVE: To describe Anorexia Nervosa in a patient from the Middle-East where
      this condition is believed to be rare. METHOD: The diagnosis of Anorexia Nervosa
      was based on detailed history and physical examination, and was in accordance
      with DSM-IV diagnostic criteria. DISCUSSION: Anorexia Nervosa should not be
      overlooked in Middle-Eastern cultures. Local values may play an important role in
      the management of the disease.

PMID- 19115365
TI  - Body dissatisfaction and the effects of perceptual exposure on body norms and
      ideals.
AB  - OBJECTIVE: Body dissatisfaction is of high prevalence among women all over the
      Western world. It is often suggested that sociocultural processes are the main
      cause of such widespread dissatisfaction. Here, we consider how perceptual
      effects may influence ideas of body normality and body ideals. METHOD: Women who
      varied on a measure of body dissatisfaction rated a range of bodies for how
      normal and ideal they looked. They were exposed to either thin or fat bodies, and
      then they rerated the bodies. RESULTS: Women's perceptions of body normality and
      ideal were easily malleable by exposure. In addition, greater body
      dissatisfaction and internalization of the thin Western ideal were related to (i)
      a smaller most normal and ideal body, (ii) a greater discrepancy between the most
      normal and most ideal-rated body, and (iii) a reduced effect of exposure to fat
      bodies. DISCUSSION: Reduced updating of perceptions of body normality and body
      ideals in response to experience may be one mechanism that maintains body
      dissatisfaction.

PMID- 19115366
TI  - Dysfunctional schemas and eating pathology in overweight youth: a case-control
      study.
AB  - OBJECTIVE: This study aimed to investigate in overweight adolescents the
      association of dysfunctional schemas (negative basic beliefs about the self and
      one's relationships with others) on one hand and eating disorder (ED) symptoms
      and depression on the other hand. METHOD: Participants were 32 overweight
      adolescents experiencing loss of control over eating (LC) and 32 overweight
      youngsters experiencing no loss of control over eating (NoLC), matched on
      referral status, age, gender, and degree of overweight. Adolescents were
      interviewed with the Eating Disorder Examination-Child version and completed the
      Young Schema Questionnaire and the Children's Depression Inventory. RESULTS: The
      LC group displayed a greater severity of dysfunctional schemas than the NoLC
      group. Maladaptive schemas were related to ED cognitions, dietary restraint
      attitudes, and depressive symptoms. DISCUSSION: In overweight youngsters, ED
      symptoms are associated with dysfunctional thinking patterns and negative affect.

PMID- 19115367
TI  - Primary care physicians' knowledge of and attitudes toward the eating disorders:
      do they affect clinical actions?
AB  - OBJECTIVE: This study examined the influence of primary care physicians'
      knowledge of and attitudes to eating disorders on their treatment decisions.
      METHOD: A sample of primary care physicians completed self-report measures on
      eating disorders and their attitudes towards such patients. They also indicated
      their diagnosis and treatment decisions in response to case vignettes. RESULTS:
      Physicians had substantial gaps in knowledge of the eating disorders. Attitudes
      to anorexia nervosa clustered differently to those toward patients with bulimia
      nervosa. However, for both disorders, the factor that explained the most variance
      was illness duration and consequences. There was no association of knowledge and
      attitudes, and these variables did not predicted the likelihood of diagnosing an
      eating disorder. However, those with higher knowledge scores were more likely to
      ensure that a follow-up appointment took place, particularly when they held the
      attitude that people with anorexia nervosa had personal control over their
      problem. DISCUSSION: There is a need for greater education of primary care
      physicians regarding the diagnosis and treatment of the eating disorders, and for
      that information to be more readily accessible when it is needed. Their clinical
      actions need to be guided by more objective sources of information and protocols.

PMID- 19115368
TI  - Slow-growing craniopharyngioma masquarading as early-onset eating disorder: two
      cases.
AB  - BACKGROUND: Craniopharyngiomas are slow-growing tumors, which can either be
      asymptomatic or present themselves with visual, neuropsychiatric or endocrine
      disturbances. Eating disorders (EDs) are syndromes with unknown etiology,
      associated with multiple endocrine abnormalities. In pediatric cases the
      presentation of EDs may differ markedly from those of adults. OBJECTIVE: We
      report on two pediatric patients with craniopharyngioma misinterpreted as ED.
      METHOD: Available patient records, psychiatric examinations, neuro-radiographic
      imaging, and biochemical data were evaluated. DISCUSSION: The reported cases
      illustrate the importance to consider slow-growing craniopharyngioma in ED.
      Especially in atypical ED, neuro-radiographic, ophthalmologic and endocrine
      examination should be carried out. Furthermore, structural hypothalamic lesions
      in these cases mimicking features of ED, suggesting the possibility of an as yet
      unidentified structural hypothalamic disorder to be implicated in the
      etiopathogeny of ED.

PMID- 19115370
TI  - Ethnic origins of patients attending specialist eating disorders services in a
      multiethnic urban catchment area in the United Kingdom.
AB  - OBJECTIVE: This study considered the impact of ethnicity on the referral process
      for patients with eating disorders, at the levels of referral rate, diagnosis,
      and treatment offered. METHOD: A catchment area cohort of 648 patients was
      referred and assessed at specialist eating disorders services in a multiethnic
      urban area (all boroughs in South London, UK). Each patient was diagnosed and
      offered treatment (or an alternative appropriate end-point to the referral), and
      self-identified their ethnicity. For comparison purposes, the local ethnic
      minority population was taken from census data. RESULTS: Ethnic minority patients
      were substantially less likely to be referred to the services than white
      patients, relative to the local population. The ethnic minority group were more
      likely to suffer from bulimia nervosa, and less likely to be found to have no
      eating disorder. However, the treatments offered did not differ substantially
      across the ethnic groups. DISCUSSION: Referrals to specialist eating disorder
      services do not reflect local populations' ethnic composition, though this
      disparity seems to be less by the time that the patient is offered treatment. It
      will be important to determine the source of these ethnic differences, and to
      take steps to reduce them.

PMID- 19115369
TI  - Attitudes toward weight gain during pregnancy: results from the Norwegian mother
      and child cohort study (MoBa).
AB  - OBJECTIVE: To explore attitudes toward weight gain during pregnancy in women with
      and without eating disorders and across eating disorder subtypes, and to examine
      associations among weight-gain attitudes and actual gestational weight gain,
      infant birth weight, and infant size-for-gestational-age. METHOD: Pregnant women
      (35,929) enrolled in the prospective population-based Norwegian mother and child
      cohort study (MoBa) provided information at approximately week 18 of gestation
      regarding eating disorders and weight gain attitudes. We explored these variables
      in women with anorexia nervosa, bulimia nervosa, eating disorder not otherwise
      specified, purging type, and binge eating disorder (BED). RESULTS: The presence
      of an eating disorderly was associated with greater worry over gestational weight
      gain. In women without eating disorders, greater worry was associated with higher
      gestational weight gain, higher infant weights, greater likelihood of a large-for
      gestational-age infant, and reduced likelihood of a small-for-gestational-age
      infant. Women with BED who reported greater worry also experienced higher weight
      gains during pregnancy. DISCUSSION: Women with eating disorders tend to
      experience weight-gain-related worry during pregnancy. Early worry about
      gestational weight-gain may be a harbinger of high gestational gain.

PMID- 19115371
TI  - Ecological momentary assessment of affect, stress, and binge-purge behaviors: day
      of week and time of day effects in the natural environment.
AB  - OBJECTIVE: The present study examined ecological momentary assessments of
      binge/vomit behavior, mood, and type and severity of stressors in a sample of 133
      women with bulimia nervosa. METHOD: Participants completed an ecological
      momentary assessment protocol for a period of 2 weeks. RESULTS: Mixed-effects and
      multilevel logistic models revealed significant variation across time of day and
      day of the week in the occurrence of binging, vomiting, positive and negative
      affect, and the severity and types of stressful events. DISCUSSION: These
      findings explicate how momentary and daily experiences vary in the natural
      environments of women with bulimia nervosa, and document critical time periods
      for intervention.

PMID- 19115372
TI  - Emotional perception in eating disorders.
AB  - OBJECTIVE: It remains an open question whether there are basic emotional
      perception and emotional processing deficits in eating disorders (ED). The aim of
      this study was to explore deficits in emotional perception in restrictive
      anorexia nervosa (AN-R) and bulimia nervosa (BN), using visual emotional stimuli.
      METHOD: Thirty-four patients with ED (19 with BN and 15 with AN-R) were compared
      with 25 controls. Visual stimuli from the international affective picture system
      were used. RESULTS: Patients with AN-R showed increased fear when confronted with
      stimuli containing anger, whereas patients with BN showed a tendency towards
      decreased fear. There were no other fundamental differences in the emotional
      perception of fear, happiness, sadness, and anger. DISCUSSION: The finding of
      increased fear when exposed to the emotion of anger might be attributed to
      introversion and conflict avoidance of anorectic patients. No other basic
      deficiency of emotional perception was found.

PMID- 19115373
TI  - Comparison of body dissatisfaction and cosmetic rhinoplasty with levels of veil
      practicing in Islamic women.
AB  - OBJECTIVE: The relationship between Islamic veiling, body dissatisfaction, and
      desire for cosmetic rhinoplasty (CR) has not been studied. We therefore compared
      body dissatisfaction (BD), depression, self-esteem, and prevalence and desire to
      have CR in 1,771 Iranian females. METHOD: A battery of questionnaires was
      administered and participants were categorized into three groups of Islamic veil
      practicing: voluntarily and ideologically (IVP), non-complete (NCIVP), and
      Inconsiderate (IIVP). RESULTS: Despite a similar BMI, the IVP group scored
      significantly lower on BD, prevalence of dieting and exercising in order to be
      sexually appealing, and depression, higher on self-esteem, and had a lower desire
      for a CR than the two other groups. Prevalence of CR was significantly higher in
      the IIVP group than the other groups. DISCUSSION: Women who practiced more strict
      Islamic veiling techniques had increased body satisfaction and self esteem, and
      decreased depression scores and desire for CR. Consistent with other studies, our
      findings show that observance of a strict religious practice has a protective
      effect on psychological health.

PMID- 19115375
TI  - Stimulation of NMDA and AMPA glutamate receptors elicits distinct concentration
      dynamics of nitric oxide in rat hippocampal slices.
AB  - Nitric oxide ((*)NO) is an intercellular messenger implicated in memory formation
      and neurodegeneration in the hippocampus. Owing to its physical and chemical
      properties, the concentration dynamics of (*)NO is a critical issue in
      determining its bioactivity as a signaling molecule. Its production is closely
      related to glutamate N-methyl-D-aspartate (NMDA) receptors, following a rise in
      intracellular calcium levels. However, that dependent on alpha-amino-3-hydroxy-5
      methylisoxazole-4-propionate (AMPA) receptors remains elusive and controversial,
      despite reports describing a role for these receptors in other brain regions,
      largely because of lack of quantitative and dynamic measurements of (*)NO. Using
      a (*)NO-selective microsensor inserted in the diffusional spread of (*)NO in the
      CA1 region of rat hippocampal slices, we measured its real-time endogenous
      production, following activation of ionotropic glutamate receptors and under
      tissue physiological oxygen tension. Both NMDA and AMPA stimulation resulted in a
      concentration-dependent (*)NO production but encompassing distinct kinetics for
      lag phases and slower rates of (*)NO production were observed for AMPA
      stimulation. Robustness of the results was achieved instrumentally and
      pharmacologically, by means of nitric oxide synthase (NOS) inhibitors and
      antagonists of NMDA (D-(-)-2-amino-5-phosphonopentanoic acid, AP5) and AMPA (2,3
      dioxo-6-nitro-1,2,3,4-tetrahydrobenzo[f]quinoxaline-7-sulfonamide, NBQX)
      receptors. When using glutamate as a stimulus, (*)NO production was of lower
      magnitude in the presence of AP5 plus NBQX than with AP5 alone, suggesting that
      even when NMDA receptors are inhibited Ca(2+) rises to levels to induce a peak of
      (*)NO from the background. Whereas extracellular Ca(2+) was required for the
      (*)NO signals, Philanthotoxin-4,3,3 (PhTX-4,3,3) a toxin used to target Ca(2+)
      permeable AMPA receptors, attenuated (*)NO production. These observations are
      interpreted on basis of a distinct coupling between the glutamate receptors and
      neuronal NOS. A role for Ca(2+)-permeable AMPA receptors in the Ca(2+) activation
      of neuronal NOS is suggested.

PMID- 19115374
TI  - A behavioral analysis of the impact of voluntary physical activity on hippocampus
      dependent contextual conditioning.
AB  - Voluntary physical activity induces molecular changes in the hippocampus
      consistent with improved hippocampal function, but few studies have explored the
      effects of wheel running on specific hippocampal-dependent learning and memory
      processes. The current studies investigated the impact of voluntary wheel running
      on learning and memory for context and extinction using contextual fear
      conditioning which is known to be dependent on the hippocampus. When conditioning
      occurred prior to the start of 6 weeks of wheel running, wheel running had no
      effect on memory for context or extinction (assessed with freezing). In contrast,
      when wheel running occurred for 6 weeks prior to conditioning, physical activity
      improved contextual memory during a retention test 24 h later, but did not affect
      extinction learning or memory. Wheel running had no effect on freezing
      immediately after foot shock presentation during conditioning, suggesting that
      physical activity does not affect the acquisition of the context-shock
      association or alter the expression of freezing, per se. Instead, it is argued
      that physical activity improves the consolidation of contextual memories in the
      hippocampus. Consistent with improved hippocampus-dependent context learning and
      memory, 6 weeks of wheel running also improved context discrimination and reduced
      the context pre-exposure time required to form a strong contextual memory. The
      effect of wheel running on brain-derived neurotrophic factor (BDNF) messenger
      ribonucleic acid (mRNA) in hippocampal and amygdala subregions was also
      investigated. Wheel running increased BDNF mRNA in the dentate gyrus, CA1, and
      the basolateral amygdala. Results are consistent with improved hippocampal
      function following physical activity.

PMID- 19115376
TI  - Early maternal deprivation induces gender-dependent changes on the expression of
      hippocampal CB(1) and CB(2) cannabinoid receptors of neonatal rats.
AB  - Early maternal deprivation (MD) in rats (24 h, postnatal day 9-10) is a model for
      neurodevelopmental stress. There are some data proving that MD affects the
      endocannabinoid system (ECS) in a gender-dependent manner, and that these changes
      may account for the proposed schizophrenia-like phenotype of MD rats. The impact
      of MD on cannabinoid receptor distribution in the hippocampus is unknown. The aim
      of this study is to evaluate the expression of CB(1) and CB(2) receptors in
      diverse relevant subregions (DG, CA1, and CA3) of the hippocampus in 13-day-old
      rats by immunohistochemistry and densitometry. MD induced a significant decrease
      in CB(1) immunoreactivity (more marked in males than in females), which was
      mainly associated with fibers in the strata pyramidale and radiatum of CA1 and in
      the strata oriens, pyramidale, and radiatum of CA3. In contrast, MD males and
      females showed a significant increase in CB(2) immunoreactivity in the three
      hippocampal areas analyzed that was detected in neuropil and puncta in the
      stratum oriens of CA1 and CA3, and in the polymorphic cell layer of the dentate
      gyrus. A marked sex dimorphism was observed in CA3, with females exhibiting
      higher CB(1) immunoreactivity than males, and in dentate gyrus, with females
      exhibiting lower CB(2) immunoreactivity than males. These results point to a
      clear association between developmental stress and dysregulation of the ECS. The
      present MD procedure may provide an interesting experimental model to further
      address the role of the ECS in neurodevelopmental mental illnesses such as
      schizophrenia.

PMID- 19115377
TI  - Hepatocellular carcinomas in patients with metabolic syndrome often develop
      without significant liver fibrosis: a pathological analysis.
AB  - Metabolic syndrome (MS) is a newly identified risk factor in chronic liver
      disease (CLD) and hepatocellular carcinoma (HCC). The aim of this study was to
      analyze the pathological characteristics of HCC and nontumoral liver in patients
      with MS as the only risk factor for liver disease in comparison with those that
      developed in the course of other CLDs in order to provide further insight into
      the physiopathology of HCC associated with MS. HCC patients with features of MS
      as the only risk factor for liver diseases (MS group, n = 31) were compared to
      HCC patients with overt causes of CLD (CLD group, n = 81) or without causes of
      CLD (cryptogenic group, n = 16) who underwent surgical resection during the same
      period of time. Among the patients of the MS group, there were 30 males and 1
      female. In comparison with the patients with HCC of the CLD group, the patients
      with MS were older (mean age: 67+/- 7 versus 59 +/- 14 years, P < 0.01), and the
      background liver was significantly more often free of significant fibrosis (F0
      F2: 65% in the MS group versus 26% in the CLD group, P < 0.001). In addition,
      HCCs associated with MS were more often well differentiated (65% versus 28%, P <
      0.001). Five HCCs, all from the MS group, developed on a preexisting liver cell
      adenoma, with three of them showing typical histological features of
      telangiectatic adenoma. CONCLUSION: This study shows that HCCs in patients with
      features of MS as the only risk factor for liver disease have distinct
      morphological characteristics and mainly occur in the absence of significant
      fibrosis in the background liver. In addition, some of them arise through
      malignant transformation of a preexisting liver cell adenoma.

PMID- 19115378
TI  - Cell cycle inhibition attenuates microglial proliferation and production of IL
      1beta, MIP-1alpha, and NO after focal cerebral ischemia in the rat.
AB  - We recently showed that suppressing cell cycle progression inhibited reactive
      astrogliosis and promoted neuronal survival in an acute focal cerebral ischemia
      rat model. However, it remains unclear whether and to what extent the beneficial
      effects of cell cycle inhibition might also be attributed to the inhibition of
      microglial proliferation and cytokine/chemokine production. In this study, we
      showed that application of the cell cycle inhibitor roscovitine before middle
      carotid artery occlusion (MCAO) in the rat inhibited microglial proliferation and
      cytokine/chemokine production, and reduced the number of cell-cycle-related
      proteins including cyclin A, cyclin B, and cyclin E. All of these microglia
      related changes may contribute to roscovitine's effect on reducing neuronal
      apoptosis and infarct volume, thus improving neurological scores. Using the BV-2
      microglia cell line, we showed that roscovitine not only inhibited oxygen-glucose
      deprivation (OGD) induced cell cycle activation by arresting the cells at G1/S
      and G2/M in a dose-dependent manner, but it also inhibited interleukin-1 beta (IL
      1beta), macrophage inflammatory protein-1alpha (MIP-1alpha), and nitric oxide
      (NO) production. These results suggest that cell cycle modulation results in
      neuroprotection in ischemia, mediated at least in part through inhibition of
      microglia proliferation and production of inflammatory cytokines such as IL
      1beta, MIP-1alpha, and NO.

PMID- 19115379
TI  - Lysophosphatidylcholine induces glial cell activation: role of rho kinase.
AB  - Lysophosphatidylcholine (LPC), a major phospholipid component of atherogenic
      oxidized LDL, is implicated in atherosclerosis and, recently, in
      neurodegenerative diseases. We investigated the immunomodulatory functions of LPC
      in the central nervous system (CNS) using both an in vivo rat model, and in vitro
      culture systems of human primary astrocytes and a microglia cell line, HMO6.
      Compared with PBS injection, 20 nmol LPC-injection into the rat striatum
      increased astrocyte and microglial accumulation and elevated iNOS expression;
      concomitantly a time-dependent decrease in number of neurons was exhibited. In
      vitro studies on astrocytes and HMO6 cells showed that LPC increased the gene
      expression of proinflammatory factors IL-1beta, COX-2, and GM-CSF. LPC also
      induced chemotactic responses in HMO6 cells. Inhibition of rho kinase by fasudil,
      Y27632, or expressing a dominant negative form of rho kinase inhibited the LPC
      induced IL-1beta mRNA expression in both astrocytes and HMO6. Moreover,
      intraperitoneal fasudil injection inhibited the LPC-induced microglial
      accumulation and iNOS expression and also was effective in protecting against
      neuronal loss. Silencing G2A, a specific receptor for LPC, inhibited
      proinflammatory gene expression and HMO6 migration. Overall, our results indicate
      that LPC induced considerable neuroinflammatory reactivity in glia mediated by
      rho kinase-dependent pathways with inhibition of these pathways conferring
      significant extents of neuroprotection.

PMID- 19115381
TI  - Stereological estimates of alveolar number and size and capillary length and
      surface area in mice lungs.
AB  - The major function of the lung is gas exchange and depends on alveolar and
      capillary parameters such as surface area and volume. The number of alveoli may
      report on the nature of structural changes in lung parenchyma during development,
      illness or changing environmental factors. We therefore developed an efficient
      and easily applicable stereological design for estimating and monitoring these
      structural parameters in the mouse lung. The estimation of volume fractions of
      different lung compartments has been carried out by point counting. A combination
      of cycloid grids superimposed on vertical sections was used to estimate the
      capillary surface area with isotropic test lines. Capillary length could be
      measured using the harmonic mean of the surface weighted diameter. The Euler
      characteristic applied in the physical fractionator with varying but known
      sampling fractions (Horovitz-Thompson estimator) enabled us to estimate alveolar
      number. In adult mice lungs, we obtained total values for alveolar number of 2.31
      x 10(6) alveoli in a pair of lungs, alveolar surface area of 82.2 cm(2),
      capillary surface area of 124 cm(2), and capillary length of 1.13 km. All values
      are corrected for tissue shrinkage. With this study we present a highly efficient
      combination of several design-based stereological tools for the unbiased
      estimation of alveolar number and volume as well as length, surface area, and
      diameter of capillaries in the mice lung. Anat Rec, 292:113-122, 2009. (c) 2008
      Wiley-Liss, Inc.

PMID- 19115380
TI  - Cannabinoid CB2 receptor agonists protect the striatum against malonate toxicity:
      relevance for Huntington's disease.
AB  - Cannabinoid agonists might serve as neuroprotective agents in neurodegenerative
      disorders. Here, we examined this hypothesis in a rat model of Huntington's
      disease (HD) generated by intrastriatal injection of the mitochondrial complex II
      inhibitor malonate. Our results showed that only compounds able to activate CB2
      receptors were capable of protecting striatal projection neurons from malonate
      induced death. That CB2 receptor agonists are neuroprotective was confirmed by
      using the selective CB2 receptor antagonist, SR144528, and by the observation
      that mice deficient in CB2 receptor were more sensitive to malonate than wild
      type animals. CB2 receptors are scarce in the striatum in healthy conditions, but
      they are markedly upregulated after the lesion with malonate. Studies of double
      immunostaining revealed a significant presence of CB2 receptors in cells labeled
      with the marker of reactive microglia OX-42, and also in cells labeled with GFAP
      (a marker of astrocytes). We further showed that the activation of CB2 receptors
      significantly reduced the levels of tumor necrosis factor-alpha (TNF-alpha) that
      had been increased by the lesion with malonate. In summary, our results
      demonstrate that stimulation of CB2 receptors protect the striatum against
      malonate toxicity, likely through a mechanism involving glial cells, in
      particular reactive microglial cells in which CB2 receptors would be upregulated
      in response to the lesion. Activation of these receptors would reduce the
      generation of proinflammatory molecules like TNF-alpha. Altogether, our results
      support the hypothesis that CB2 receptors could constitute a therapeutic target
      to slowdown neurodegeneration in HD.

PMID- 19115382
TI  - GFAP promoter driven transgenic expression of PDGFB in the mouse brain leads to
      glioblastoma in a Trp53 null background.
AB  - Glioblastomas are the most common and malignant astrocytic brain tumors in human
      adults. The tumor suppressor gene TP53 is commonly mutated and/or lost in
      astrocytic brain tumors and the TP53 alterations are often found in combination
      with excessive growth factor signaling via PDGF/PDGFRalpha. Here, we have
      generated transgenic mice over-expressing human PDGFB in brain, under control of
      the human GFAP promoter. These mice showed no phenotype, but on a Trp53 null
      background a majority of them developed brain tumors. This occurred at 2-6 months
      of age and tumors displayed human glioblastoma-like features with integrated
      development of Pdgfralpha+ tumor cells and Pdgfrbeta+/Nestin+ vasculature. The
      transgene was expressed in subependymal astrocytic cells, in glia limitans, and
      in astrocytes throughout the brain substance, and subsequently, microscopic tumor
      lesions were initiated equally in all these areas. With tumor size, there was an
      increase in Nestin positivity and variability in lineage markers. These results
      indicate an unexpected plasticity of all astrocytic cells in the adult brain, not
      only of SVZ cells. The results also indicate a contribution of widely distributed
      Pdgfralpha+ precursor cells in the tumorigenic process.

PMID- 19115383
TI  - Live imaging of amyotrophic lateral sclerosis pathogenesis: disease onset is
      characterized by marked induction of GFAP in Schwann cells.
AB  - Amyotrophic lateral sclerosis (ALS) is a late-onset neurological disease
      characterized by progressive loss of motor neurons. At present, the pathological
      events precipitating disease onset and the exact pattern of disease progression
      are not fully understood. Recent studies suggest that glial cells, in particular
      activated astrocytes, can release factors that can directly kill motor neurons.
      To further investigate the involvement of glial cells (astrocytes and Schwann
      cells) in the pathogenesis of ALS, we generated ALS-(GFAP-luciferase/SOD(G93A))
      reporter mouse in which upregulation of glial fibrillary acidic protein (GFAP)
      can be visualized from live animals throughout the different stages of disease.
      Our results suggest that the disease in mice is initiated simultaneously in the
      spinal cord and in the peripheral nerves and is characterized by several cycles
      of GFAP upregulation. Immunohistochemical analysis confirmed that the induction
      GFAP bioluminescence signals were associated with the significant increases in
      GFAP immunoreactivity. The first pathological GFAP signals occurring at 25-30
      days were asymptomatic and detectable at the level of lumbar spinal cord
      projections and at the periphery. These early events were then followed by GFAP
      promoter inductions that were associated with the distinct clinical symptoms. As
      expected, the onset of paralysis (112 days) was associated with the gradual and
      marked GFAP upregulation in the spinal cord. Interestingly, however, the disease
      onset (90 days) was characterized by sharp and synchronized induction of GFAP in
      peripheral nerve Schwann cells suggesting that peripheral nerves
      pathology/denervation and associated Schwann cell stress may play an important
      role in the ALS pathogenesis.

PMID- 19115384
TI  - Developmental and post-injury cortical gliogenesis: a genetic fate-mapping study
      with Nestin-CreER mice.
AB  - The primary sources of cortical gliogenesis, either during development or after
      adult brain injury, remain uncertain. We previously generated Nestin-CreER mice
      to fate-map the progeny of radial glial cells (RG), a source of astrocytes and
      oligodendrocytes in the nervous system. Here, we show that Nestin-CreER mice
      label another population of glial progenitors, namely the perinatal
      subventricular zone (SVZ) glioblasts, if they are crossed with stop-floxed EGFP
      mice and receive tamoxifen in late embryogenesis (E16-E18). Quantification showed
      E18 tamoxifen-induction labeled more perinatal SVZ glioblasts than RG and
      transitional RG combined in the newborn brain (54% vs. 22%). Time-lapse
      microscopy showed SVZ-glioblasts underwent complex metamorphosis and often
      reciprocal transformation into transitional RG. Surprisingly, the E10-dosed RG
      progenitors produced astrocytes, but no oligodendrocytes, whereas E18-induction
      fate-mapped both astrocytes and NG2+ oligodendrocyte precursors in the postnatal
      brain. These results suggest that cortical oligodendrocytes mostly derive from
      perinatal SVZ glioblast progenitors. Further, by combining genetic fate-mapping
      and BrdU-labeling, we showed that cortical astrocytes cease proliferation soon
      after birth (<P10) and only undergo nonproliferative gliosis (i.e., increased
      GFAP expression without cell-division) after stab-wound injury in adult brains.
      By contrast, 9.7% of cortical NG2+ progenitors remained mitotic at P29, and the
      ratio rose to 13.8% after stab-wound injury. Together, these results suggest NG2+
      progenitors, rather than GFAP+ astrocytes, are the primary source of
      proliferative gliosis after adult brain injury.

PMID- 19115385
TI  - Secretory phospholipase A2 plays an essential role in microglial inflammatory
      responses to Mycobacterium tuberculosis.
AB  - In previous studies, we have shown that reactive oxygen species (ROS)-mediated
      inflammatory signaling is essential for microglial proinflammatory responses to
      Mycobacterium tuberculosis (Mtb). To further investigate the molecular mechanisms
      governing these processes, we sought to describe the role of phospholipase A(2)
      (PLA(2)) in Mtb-induced ROS generation and inflammatory mediator release by
      microglia. Inhibition of secretory PLA(2) (sPLA(2)), but not cytosolic PLA(2)
      (cPLA(2)), profoundly abrogated Mtb-mediated ROS release, the generation of
      various inflammatory mediators (tumor necrosis factor, interleukin-6,
      cyclooxygenase-2, inducible nitric oxide synthase, and matrix metalloproteinase-2
      and -9), and the activation of nuclear factor (NF)-kappaB and MAPKs (ERK1/2, p38,
      and JNK/SAPK) by murine microglial BV-2 cells or primary mixed glial cells.
      Interruption of the Ras/Raf-1/MEK1/ERK1/2 pathway abolished Mtb-induced sPLA(2)
      activity, whereas the blockage of JNK/SAPK or p38 activity had no effect.
      Specific inhibition of sPLA(2), but not cPLA(2), suppressed the upregulation of
      ERK1/2 phosphorylation by Mtb stimulation, suggesting the existence of a mutual
      dependency between the ERK1/2 and sPLA(2) pathways. Moreover, examination of the
      protein kinase C (PKC) family revealed that classical PKCs are involved in Mtb
      induced sPLA(2) activation by microglia. Taken together, our results demonstrate
      for the first time that sPLA(2), either through pathways comprising Ras/Raf
      1/MEK1/ERK1/2 or the classical PKC family, plays an essential role in Mtb
      mediated ROS generation and inflammatory mediator release by microglial cells.

PMID- 19115386
TI  - The Alzheimer's disease drug memantine increases the number of radial glia-like
      progenitor cells in adult hippocampus.
AB  - New neurons are continuously generated in the hippocampus of the adult mammalian
      brain, and N-methyl-D-aspartate receptor (NMDA-R) antagonists have been found to
      increase the number of newly generated neurons in the dentate gyrus (DG) of the
      adult hippocampus. In this study, we examined the effect of memantine, an NMDA-R
      antagonist that is clinically used for the treatment of Alzheimer's disease, on
      primary progenitor cells exhibiting a radial glia-like (RGL) morphology in the
      DG. We injected 3-month-old mice with memantine (50 mg/kg body weight,
      intraperitoneally [i.p.]); 3 days later, we injected the mice with 5-bromo-2
      deoxyuridine (BrdU; 75 mg/kg body weight, i.p.). We then counted the number of
      BrdU-labeled RGL progenitor cells in the DG 1 or 7 days after the BrdU-injection.
      The number of BrdU-labeled RGL progenitor cells had increased significantly by
      5.1-fold on day 1 and by 13.7-fold on day 7 after BrdU-injection.
      Immunohistochemical staining revealed that the BrdU-labeled RGL progenitor cells
      expressed two primary progenitor cell marker proteins, nestin and Sox2. These
      results clearly demonstrated that memantine promotes the proliferation of RGL
      progenitor cells. We also found that memantine increased the ratio of
      horizontally aligned RGL progenitor cells, which are probably produced by
      symmetric division. These findings suggest that memantine increases the
      proliferation of primary progenitor cells and expands the primary progenitor cell
      pool in the adult hippocampus by stimulating symmetric division.

PMID- 19115387
TI  - Sodium channel activity modulates multiple functions in microglia.
AB  - Microglia provide surveillance in the central nervous system and become activated
      following tissue insult. Detailed mechanisms by which microglia detect and
      respond to their environment are not fully understood, but it is known that
      microglia express a number of surface receptors and ion channels, including
      voltage-gated sodium channels, that participate in transduction of external
      stimuli to intra-cellular responses. To determine whether activated microglia are
      affected by the activity of sodium channels, we examined the expression of sodium
      channel isoforms in cultured microglia and the action of sodium channel blockade
      on multiple functions of activated microglia. Rat microglia in vitro express
      tetrodotoxin (TTX)-sensitive sodium channels Nav1.1 and Nav1.6 and the TTX
      resistant channel Nav1.5, but not detectable levels of Nav1.2, Nav1.3, Nav1.7,
      Nav1.8, and Nav1.9. Sodium channel blockade with phenytoin (40 microM) and TTX
      (0.3 microM) significantly reduced by 50-60% the phagocytic activity of microglia
      activated with lipopolysaccharide (LPS); blockade with 10 microM TTX did not
      further reduce phagocytic activity. Phenytoin attenuated by approximately 50% the
      release of IL-1 alpha, IL-1 beta, and TNF-alpha from LPS-stimulated microglia,
      but had minimal effects on the release of IL-2, IL-4, IL-6, IL-10, MCP-1, and TGF
      alpha. TTX (0.3 microM) reduced, but to a smaller extent, the release of IL-1
      alpha, IL-1 beta, and TNF-alpha from activated microglia. Phenytoin and TTX also
      significantly decreased by approximately 50% adenosine triphosphate-induced
      migration by microglia; studies with microglia cultured from med mice (which lack
      Nav1.6) indicate that Nav1.6 plays a role in microglial migration. The results
      demonstrate that the activity of sodium channels contributes to effector roles of
      activated microglia.

PMID- 19115388
TI  - Supra-normal age-linked retrograde amnesia: lessons from an older amnesic (H.M.).
AB  - MacKay and James (2001) demonstrated greater-than-normal retrograde amnesia (RA)
      for lexical-semantic information in amnesic H.M., a deficit that worsened with
      aging or represented supranormal age-linked RA (SARA). The present experiments
      extend these earlier observations to new types of information. Experiment 1
      participants (H.M. and carefully matched memory-normal controls) named pictures
      on the Boston Naming Test and H.M. correctly named reliably fewer pictures with
      low frequency names, he produced unusual naming errors, and he benefited reliably
      less than the controls from phonological cues to the target word. Experiment 2
      participants recalled irregularly-spelled aspects of familiar words in a two
      choice recognition memory task and H.M. chose the correct spelling reliably less
      often than the controls. Experiment 3 participants read low frequency words aloud
      at age 73 and H.M. produced reliably more reading errors than the controls.
      Results of all three experiments indicate supranormal RA (SRA) for information
      once familiar to H.M. and comparisons with earlier studies using similar or
      identical stimuli indicated that H.M.'s SRA has worsened with aging from 1980 to
      1999. In short, H.M. exhibits SARA for phonological and orthographic information,
      consistent with the MacKay and James results and with interactions between aging
      and amnesia predicted under binding theory.

PMID- 19115390
TI  - Excitability changes within transverse lamellae of dentate granule cells and
      their longitudinal spread following orthodromic or antidromic activation.
AB  - The functional organization of the perforant path input to the dentate gyrus of
      the exposed hippocampus was studied in adult rabbits anesthetized with urethane
      and chloralose. Electrical stimulation of perforant path fibers caused excitation
      of granule cells along narrow, nearly transverse strips (lamellae) of tissue.
      Stimulation of granule cell axons (mossy fibers) in CA3 caused antidromic
      activation of granule cells along similar strips. Paired-pulse stimulation
      revealed marked changes in granule cell excitability both within a lamella (on
      line) and for several mm off-line along the septo-temporal axis of the dentate
      gyrus. After the first pulse, granule cells were inhibited for up to about 100 ms
      and then facilitated for up to hundreds of ms. Feedback activity along mossy
      fiber collaterals exciting local inhibitory and excitatory neurons appeared to
      dominate in producing on- and off-line inhibition and facilitation. Neurons
      mediating these effects could be inhibitory basket cells and other inhibitory
      interneurons targeting granule cells on- and off-line. In addition, excitatory
      mossy cells with far reaching, longitudinally running axons could affect off-line
      granule cells by exciting them directly or inhibit them indirectly by exciting
      local inhibitory interneurons. A scheme for dentate gyrus function is proposed
      whereby information to the dentate gyrus becomes split into interacting
      transverse strips of neuronal assemblies along which temporal processing occurs.
      A matrix of neuronal assemblies thus arises within which fragments of events and
      experiences is stored through the plasticity of synapses within and between the
      assemblies. Similar fragments may then be recognized at later times allowing
      memories of the whole to be created by pattern completion at subsequent
      computational stages in the hippocampus.

PMID- 19115389
TI  - Ablation of lung epithelial cells deregulates FGF-10 expression and impairs lung
      branching morphogenesis.
AB  - Epithelial-mesenchymal interactions are essential for tissue patterning during
      organogenesis. Distal lung epithelium and its adjacent mesenchyme comprise the
      epithelial-mesenchymal signaling unit that regulates lung branching
      morphogenesis. Tissue recombination experiments have demonstrated the importance
      of mesenchymal signals in inducing lung epithelial differentiation and branching,
      but the role of the epithelium in regulating mesenchymal signals has not been
      well characterized. Using transgenic mice, we ablated distal lung epithelial
      cells during lung development by inducing the expression of a constitutively
      active proapoptotic Bax protein under the surfactant protein C (SP-C) promoter.
      We found that epithelial cell ablation results in impaired lung branching
      morphogenesis, which progresses to emphysematous airspaces in the adults.
      Mesenchymal expression of fibroblast growth factor 10 (Fgf-10), whose strict
      spatial and temporal expression is critical for proper lung branching
      morphogenesis, is disrupted and loses its localized pattern. Interestingly, the
      expression of sonic hedgehog (Shh), an epithelial gene known to modulate Fgf-10
      expression, is unchanged, indicating the existence of other distal epithelial
      signals that regulate mesenchymal Fgf-10expression. We propose that distal SP-C
      expressing lung epithelial cells provide essential signals for the downregulation
      of Fgf-10 expression in the distal mesenchyme during lung development. 292:123
      130, 2009. (c) 2008 Wiley-Liss, Inc.

PMID- 19115391
TI  - Impaired in vivo synaptic plasticity in dentate gyrus and spatial memory in
      juvenile rats induced by prenatal morphine exposure.
AB  - Prenatal morphine exposure induces neurobiological changes, including deficits in
      learning and memory, in juvenile rat offspring. However the effects of this
      exposure on hippocampal plasticity, which is critical for learning and memory
      processes, are not well understood. The present study investigates the
      alterations of spatial memory and in vivo hippocampal synaptic plasticity in
      juvenile rats prenatally exposed to morphine. On gestation days 11-18, pregnant
      rats were randomly chosen to be injected twice daily with morphine or saline.
      Each juvenile offspring (postnatal day 22-31) performed one two-trial Y-maze task
      to evaluate spatial memory. Afterwards, the in vivo field excitatory postsynaptic
      potential (fEPSP) and population spike (PS) were recorded in the perforant path
      dentate gyrus (DG) pathway in the hippocampus. Prenatal morphine exposure reduced
      depotentiation (DP), but not long-term potentiation (LTP), of the EPSP slope.
      However, both LTP and DP of the EPSP slope were depressed in prenatal morphine
      exposed juvenile offspring. The morphine group also showed poorer performance for
      the Y-maze task than the control group. Depressed PS LTP, but not EPSP LTP, in
      the morphine group suggested that prenatal morphine exposure changed GABAergic
      inhibition, which mediates EPSP-spike potentiation. Then a loss of GABA
      containing neurons in the DG area of the morphine group was observed using
      immunohistochemistry. Taken together, our results suggest that prenatal morphine
      exposure impairs the juvenile offspring's dentate synaptic plasticity and spatial
      memory, and that decreased GABAergic inhibition may play a role in these effects.
      These findings might contribute to an explanation for the cognitive deficits in
      children whose mothers abuse opiates during pregnancy.

PMID- 19115392
TI  - The effects of IL-1 receptor antagonist on beta amyloid mediated depression of
      LTP in the rat CA1 in vivo.
AB  - Beta-amyloid (Abeta) is a neuro-peptide implicated in the pathogenesis of
      Alzheimer's disease (AD). Abeta-peptide is known to disrupt cellular processes,
      including synaptic plasticity. To date, the precise mechanisms leading to the
      Abeta-mediated impairment of normal neurophysiological function still remains
      elusive. A rise in the pro-inflammatory cytokine interleukin-1-beta (IL-1beta)
      has been previously reported, following Abeta peptide insult. IL-1beta in turn,
      activates a cascade of pro-apoptotic markers, gradually leading to cell death. In
      this work, we have investigated the possible protective effects of interleukin-1
      receptor antagonist (IL-1ra) on the effects of Abeta-peptide on long-term
      potentiation (LTP) in the CA1 region of the rat hippocampus in vivo. We observed
      a significant depression of LTP in the group of animals that received
      intracerebroventricular (icv) injection of Abeta-peptide (1-40) compared with
      control animals injected with vehicle. Administration of IL-1ra alone (icv) also
      resulted in a depression of LTP; however, there was no change in the baseline
      synaptic response. Combined injection of Abeta(1-40) + IL-1ra caused an
      attenuation of the effects observed with Abeta(1-40) alone for a period of up to
      15 min following LTP induction; rescuing post-tetanicpotentiation (PTP).
      Gradually however, EPSP-values declined to produce a level of LTP similar to that
      observed following treatment with Abeta(1-40) alone. These results suggest that
      the acute Abeta-mediated impairment of PTP and LTP may be partial as a result of
      activation of an inflammatory response and the release of IL-1beta. The
      attenuation of plasticity by IL-1ra alone supports the theory that low levels of
      IL-1beta are required for normal synaptic plasticity. The limited rescue of the
      Abeta-mediated effects on LTP, in the presence of IL-1ra, may represent the short
      half life found with this receptor antagonist in vivo.

PMID- 19115394
TI  - Enhanced hippocampal neurogenesis in the absence of microglia T cell interaction
      and microglia activation in the murine running wheel model.
AB  - Recently, activated microglia have been shown to be involved in the regulation of
      several aspects of neurogenesis under certain experimental conditions both in
      vitro and in vivo. A neurogenesis supportive microglia phenotype has been
      suggested to arise from the interaction of microglia with homing encephalitogenic
      T cells. However, a unified hypothesis regarding the exact nature of microglia
      activity that is supportive of neurogenesis is yet missing from the field. Our
      aim was to investigate the connection between microglia activity and adult
      hippocampal neurogenesis under physiological conditions. To address this question
      we compared the level of microglia activation in the hippocampus of mice, which
      had access to a running wheel for 10 days and that of sedentary controls.
      Surprisingly, despite elevated levels of proliferation of neural precursors and
      survival of newborn neurons in the dentate gyrus microglia remained in a
      "resting" state morphologically, antigenically, and at the transcriptional level.
      Moreover, neither T cells nor MHCII expressing microglia were present in the
      hippocampal brain parenchyma. Though microglia in the dentate gyrus of the
      runners proliferated at a higher level than in the sedentary controls, this
      difference was also present in non-neurogenic sites. Therefore, our findings
      suggest that classical signs of microglia activation and microglia activation
      arising from interaction with T cells in particular are not a prerequisite for
      the activity-induced increase in adult hippocampal neurogenesis in C57Bl/6 mice.
      Thus, our results draw attention on the species and model differences that might
      exist regarding the regulation of adult hippocampal neurogenesis.

PMID- 19115393
TI  - Adult-onset deficiency in growth hormone and insulin-like growth factor-I alters
      oligodendrocyte turnover in the corpus callosum.
AB  - Growth hormone (GH) and insulin-like growth factor-I (IGF-I) provide trophic
      support during development and also appear to influence cell structure, function
      and replacement in the adult brain. Recent studies demonstrated effects of the
      GH/IGF-I axis on adult neurogenesis, but it is unclear whether the GH/IGF-I axis
      influences glial turnover in the normal adult brain. In the current study, we
      used a selective model of adult-onset GH and IGF-I deficiency to evaluate the
      role of GH and IGF-I in regulating glial proliferation and survival in the adult
      corpus callosum. GH/IGF-I-deficient dwarf rats of the Lewis strain were made
      GH/IGF-I replete via twice daily injections of GH starting at postnatal day 28
      (P28), approximately the age at which GH pulse amplitude increases in developing
      rodents. GH/IGF-I deficiency was initiated in adulthood by removing animals from
      GH treatment. Quantitative analyses revealed that adult-onset GH/IGF-I deficiency
      decreased cell proliferation in the white matter and decreased the survival of
      newborn oligodendrocytes. These findings are consistent with the hypothesis that
      aging-related changes in the GH/IGF-I axis produce deficits in ongoing turnover
      of oligodendrocytes, which may contribute to aging-related cognitive changes and
      deficits in remyelination after injury.

PMID- 19115395
TI  - P2 receptor-mediated stimulation of the PI3-K/Akt-pathway in vivo.
AB  - ATP acts as a growth factor as well as a toxic agent by stimulating P2 receptors.
      The P2 receptor-activated signaling cascades mediating cellular growth and cell
      survival after injury are only incompletely understood. Therefore, the aim of the
      present study was to identify the role of the phosphoinositide 3 kinase (PI3
      K/Akt) and the mitogen-activated protein kinase/extracellular signal regulated
      protein kinase (MAPK/ERK) pathways in P2Y receptor-mediated astrogliosis after
      traumatic injury and after microinfusion of ADP beta S (P2Y(1,12,13) receptor
      agonist) into the rat nucleus accumbens (NAc). Mechanical damage and even more
      the concomitant treatment with ADP beta S, enhanced P2Y(1) receptor-expression in
      the NAc, which could be reduced by pretreatment with the P2X/Y receptor
      antagonist PPADS. Quantitative Western blot analysis indicated a significant
      increase in phosphorylated (p)Akt and pERK1/2 2 h after ADP beta S
      microinjection. Pretreatment with PPADS or wortmannin abolished the up-regulation
      of pAkt by injury alone or ADP beta S-treatment. The ADP beta S-enhanced
      expression of the early apoptosis marker active caspase 3 was reduced by PPADS
      and PD98059, but not by wortmannin. Multiple immunofluorescence labeling
      indicated a time-dependent expression of pAkt and pMAPK on astrocytes and neurons
      and additionally the colocalization of pAkt, pMAPK, and active caspase 3 with the
      P2Y(1) receptor especially at astrocytes. In conclusion, the data show for the
      first time the involvement of PI3-K/Akt-pathway in processes of injury-induced
      astroglial proliferation and anti-apoptosis via activation of P2Y(1) receptors in
      vivo, suggesting specific roles of P2 receptors in glial cell pathophysiology in
      neurodegenerative diseases.

PMID- 19115396
TI  - Subtype-specific oligodendrocyte dynamics in organotypic culture.
AB  - The morphogenesis of oligodendrocytes is essential for central nervous system
      myelin formation and the rapid propagation of axon potentials through saltatory
      conduction. However, the discrete cellular events involved in the three
      dimensional maturation of oligodendrocytes remain to be fully described. To
      address this, we followed the developmental stages of oligodendrocytes in mouse
      organotypic hippocampal slice cultures for 7-60 days using viral-mediated gene
      delivery of membrane-targeted fluorescent proteins. Using static and time-lapse
      confocal imaging, we find that postmigratory NG2-expressing cells exhibit slow
      anatomical reorganization over the course of hours. This is in direct contrast to
      oligodendrocytes that take on a promyelinating and transitional phenotype, which
      display a more complex morphology and undergo dramatic actin-dependent structural
      remodeling over just minutes. More mature myelinating oligodendrocytes, which
      have pruned most of their processes, still retain some local remodeling behavior
      at developing internodes, but in general, revert to a relatively stable state.
      Our findings provide a detailed characterization of cellular events that help
      shape oligodendrocyte morphology and likely participate in neuron-glial cell
      interactions and the process of myelination.

PMID- 19115397
TI  - Markers of physiological stress in juvenile bonobos (Pan paniscus): are enamel
      hypoplasia, skeletal development and tooth size interrelated?
AB  - A reduction in enamel thickness due to disrupted amelogenesis is referred to as
      enamel hypoplasia (EH). Linear EH in permanent teeth is a widely accepted marker
      of systemic physiological stress. An enigmatic, nonlinear form of EH commonly
      manifest in great ape and human deciduous canines (dc) is known as localized
      hypoplasia of primary canines (LHPC). The etiology of LHPC and what it signifies
      localized traumatic or systemic physiological stress-remains unclear. This report
      presents frequency data on LHPC, hypostotic cranial traits, and tooth size in a
      sample of juvenile bonobos, then tests hypotheses of intertrait association that
      improve knowledge of the etiology and meaning of LHPC. The fenestration
      hypothesis is tested using hypostotic cranial traits as a proxy for membrane bone
      ossification, and the relationship between tooth size, LHPC, and hypostosis is
      investigated. Macroscopic observations of EH, hypostotic traits, and measurements
      of buccolingual tooth size were conducted according to established standards.
      LHPC was found in 51.2% of bonobos (n = 86) and in 26% of dc teeth (n = 269).
      Hypostotic traits were observed in 55.2% of bonobos (n = 96). A test of the
      association between LHPC and hypostosis yielded nonsignificant results (chi(2) =
      2.935; P = 0.0867). Primary canines were larger in specimens with LHPC than in
      unaffected specimens (paired samples t test; udc, P = 0.011; ldc, P = 0.018), a
      result consistent with the fenestration hypothesis of LHPC pathogenesis.
      Hypostosis was not associated with differences in tooth size (P > 0.05). LHPC may
      be an indirect indicator of physiological stress, resulting from large, buccally
      displaced primary canines.

PMID- 19115398
TI  - Food mechanical properties in three sympatric species of Hapalemur in Ranomafana
      National Park, Madagascar.
AB  - We investigated mechanical dietary properties of sympatric bamboo lemurs,
      Hapalemur g. griseus, H. aureus, and H. (Prolemur) simus, in Ranomafana National
      Park, Madagascar. Each lemur species relies on bamboo, though previous behavioral
      observations found that they specialize on different parts of a common resource
      (Tan: Int J Primatol 20 1999 547-566; Tan: PhD dissertation 2000 State University
      of New York, Stony Brook). On the basis of these earlier behavioral ecology
      studies, we hypothesized that specialization on bamboo is related to differences
      in mechanical properties of specific parts. We quantified mechanical properties
      of individual plant parts from the diets of the bamboo lemur species using a
      portable tester. The diets of the Hapalemur spp. exhibited high levels of
      mechanical heterogeneity. The lemurs, however, could be segregated based on the
      most challenging (i.e., mechanically demanding) foods. Giant bamboo culm pith was
      the toughest and stiffest food eaten, and its sole lemur consumer, H. simus, had
      the most challenging diet. However, the mechanical dietary properties of H. simus
      and H. aureus overlapped considerably. In the cases where lemur species converged
      on the same bamboo part, the size of the part eaten increased with body size.
      Plant parts that were harvested orally but not necessarily masticated were the
      most demanding, indicating that food preparation may place significant loads on
      the masticatory apparatus. Finally, we describe how mechanical properties can
      influence feeding behavior. The elaborate procurement processes of H. simus
      feeding on culm pith and H. griseus and H. aureus feeding on young leaf bases are
      related to the toughnesses of protective coverings and the lemurs' exploitation
      of mechanical vulnerabilities in these plants.

PMID- 19115399
TI  - Environmental and geographic correlates of the taxonomic structure of primate
      communities.
AB  - Previous research has shown that both environmental and historical factors
      influence the taxonomic structure of animal communities; yet, the relative
      importance of these effects is not known for primates. Environmental
      characteristics shape the possible niches in a community, providing suitable
      habitats for some species and not others. Therefore, communities found in similar
      environments should display similar species compositions. Additionally, geography
      may be viewed as a surrogate for historical processes. For instance, as the
      geographic distance between communities increases, dispersal between sites is
      more limited, and the probability of historical vicariance increases. Therefore,
      communities in close proximity to each other should exhibit similar species
      compositions. The geographic location, environmental characteristics, and species
      composition of 168 primate communities were gathered from the literature.
      Canonical correspondence analyses were conducted to examine the relative effects
      of geographic distance and environmental variables on the taxonomic structure of
      communities. In addition, UPGMA cluster analyses were conducted to better
      visualize the taxonomic similarity of communities. Spatial variables were
      significant predictors of community structure in all regions. Rainfall patterns
      explained African, Malagasy, and Neotropical community structure. In addition,
      maximum temperature was also correlated with community structure in Madagascar
      and the Neotropics. No climatic variables predicted Asian community structure.
      These results demonstrate that both historical and environmental factors play a
      significant role in structuring modern primate communities; yet, the importance
      of environmental factors depend on the region in question.

PMID- 19115400
TI  - Neuroanatomical relationships of substance P-immunoreactive intrapulmonary C
      fibers and nicotinic cholinergic receptors.
AB  - Previous studies have suggested that sensory mechanisms may be important
      components of addiction to, and withdrawal from, cigarette smoking. The sensory
      and respiratory responses to nicotine are mediated, in part, by bronchopulmonary
      C-fiber afferents. Nicotine has a direct stimulatory effect on pulmonary sensory
      neurons, and nicotinic cholinergic receptors (nAChRs) composed of various
      combinations of alpha and beta subunits are known to be present in pulmonary
      ganglia. At the subcellular level, however, little is known about expression of
      nAChRs on sensory fibers in the intrapulmonary airways. The present study was
      therefore designed to evaluate the expression of nAChRs on a subset of
      intrapulmonary sensory nerve endings known to exhibit immunoreactivity for
      substance P (SP). The presence of nAChR subunits was first confirmed at the mRNA
      and protein levels in rat lung tissues by using RT-PCR and Western blot
      techniques. Then, double labeling of SP-immunoreactive (-IR) C-fibers and
      different nAChR subunits was performed. Alpha2, alpha3, alpha4, alpha5, alpha7,
      and beta2 subunits were detected at all levels of the intrapulmonary airways;
      including bronchi, terminal and respiratory bronchioles, alveolar walls, and
      alveolar macrophages. None of the nAChR subunits studied was expressed by the SP
      IR C-fibers. However, SP-expressing C-fibers were observed in close proximity to
      and intermingling with nAChR-expressing airway epithelial cells. The close
      proximity of C-fibers to nAChR-expressing airway epithelial cells suggests that a
      component of nicotinic stimulation of SP-IR C-fiber afferents may be mediated by
      endogenous chemical substances released by nAChR-expressing epithelial cells.

PMID- 19115401
TI  - Aberrant axonal projections from mammillary bodies in Pax6 mutant mice: possible
      roles of Netrin-1 and Slit 2 in mammillary projections.
AB  - Early events in the axonal tract formation from mammillary bodies remain poorly
      understood. In the present study, we reported an aberrant pattern of axonal
      projections from mammillary bodies to the dorsal thalamus in mice lacking the
      transcription factor Pax6. We found that Netrin-1 was ectopically up-regulated
      and that both Slit1 and Slit2 were down-regulated in the presumptive dorsal
      thalamus of Pax6 mutant mice. We then examined the effects of Netrin-1 and Slit2
      on the mammillary axons by in utero electroporation techniques. Netrin-1 had an
      attractive action toward the mammillary axons. Moreover, mammillary trajectories
      were disorganized in Netrin-1-deficient mice. On the other hand, Slit2 had a
      repulsive effect on the mammillary axons. These findings suggest that the
      combination of Netrin and Slit may be involved in proper axonal projection from
      the mammillary bodies and that their misexpression in the diencephalon may cause
      the misrouting of these axons in Pax6 mutant mice.

PMID- 19115402
TI  - Rho proteins are negative regulators of TLR2, TLR3, and TLR4 signaling in
      astrocytes.
AB  - The family of Toll-like receptors (TLRs) expressed by innate immune cells
      recognizes a spectrum of microbial components as well as molecules released from
      injured tissues. TLR ligation activates intracellular signaling cascades that
      culminate in the up-regulation of proinflammatory genes. We have recently
      demonstrated that the up-regulation of inflammatory cytokines mediated by TLR4 in
      astrocytes is negatively controlled by the monomeric GTPases of Rho subfamily.
      The present study was undertaken to examine further the involvement of Rho
      proteins in the inflammatory response of astrocytes elicited by the ligation of
      three TLRs that use divergent signaling pathways. Astrocyte cultures established
      from newborn rat brains were challenged with ligands of TLR2, TLR3, and TLR4. The
      expression of genes encoding interleukin (IL)-1beta, IL-6, tumor necrosis factor
      alpha (TNFalpha), interferon-beta (IFNbeta), and inducible nitric oxide synthase
      (NOS2) was up-regulated 24 hr after the challenge as determined by real-time RT
      PCR. Pretreatment of the cells with toxin B, which specifically inactivates Rho
      proteins, enhanced the up-regulation of gene expression. The extent of this
      enhancement was both receptor and gene dependent. The enhancing effect of Rho
      protein inactivation was also evident at the protein level of IL-6 and NOS2 as
      revealed by ELISA and immunoblot analyses, respectively. These results suggest
      that Rho proteins control TLR-mediated up-regulation of inflammatory genes in
      astrocytes by interfering with multiple events along the signaling pathways.

PMID- 19115403
TI  - The action of pulse-modulated GSM radiation increases regional changes in brain
      activity and c-Fos expression in cortical and subcortical areas in a rat model of
      picrotoxin-induced seizure proneness.
AB  - The action of the pulse-modulated GSM radiofrequency of mobile phones has been
      suggested as a physical phenomenon that might have biological effects on the
      mammalian central nervous system. In the present study, GSM-exposed picrotoxin
      pretreated rats showed differences in clinical and EEG signs, and in c-Fos
      expression in the brain, with respect to picrotoxin-treated rats exposed to an
      equivalent dose of unmodulated radiation. Neither radiation treatment caused
      tissue heating, so thermal effects can be ruled out. The most marked effects of
      GSM radiation on c-Fos expression in picrotoxin-treated rats were observed in
      limbic structures, olfactory cortex areas and subcortical areas, the dentate
      gyrus, and the central lateral nucleus of the thalamic intralaminar nucleus
      group. Nonpicrotoxin-treated animals exposed to unmodulated radiation showed the
      highest levels of neuronal c-Fos expression in cortical areas. These results
      suggest a specific effect of the pulse modulation of GSM radiation on brain
      activity of a picrotoxin-induced seizure-proneness rat model and indicate that
      this mobile-phone-type radiation might induce regional changes in previous
      preexcitability conditions of neuronal activation.

PMID- 19115404
TI  - Deleterious effects of minocycline after in vivo target deprivation of
      thalamocortical neurons in the immature, metallothionein-deficient mouse brain.
AB  - Compared with adults, immature metallothionein I and II knockout (MT(-/-)) mice
      incur greater neuronal loss and a more rapid rate of microglia accumulation after
      target deprivation-induced injury. Because minocycline has been proposed to
      inhibit microglial activation and associated production of neuroinflammatory
      factors, we investigated its ability to promote neuronal survival in the
      immature, metallothionein-deficient brain. After ablation of the visual cortex,
      10-day-old MT(-/-) mice were treated with minocycline or saline and killed 24 or
      48 hr after injury. By means of stereological methods, the number of microglia
      and neurons were estimated in the ipsilateral dorsal lateral geniculate nucleus
      (dLGN) by an investigator blinded to the treatment. No effect on neuronal
      survival was observed at 24 hr, but 48 hr after injury, an unanticipated but
      significant minocycline-mediated increase in neuronal loss was detected. Further,
      while failing to inhibit microglial accumulation, minocycline treatment increased
      the proportion of amoeboid microglia in the ipsilateral dLGN. To understand the
      molecular mechanisms underlying this neurotoxic response, we identified
      minocycline-mediated changes in the expression of three potentially
      proapoptotic/inflammatory genes: growth arrest- and DNA damage-inducible gene
      45gamma (GADD45gamma); interferon-inducible protein 1 (IFI1), and cytokine
      induced growth factor. We also observed increased mitogen-activated protein
      kinase p38 phosphorylation with minocycline treatment. Although minocycline
      inhibited calpain activity at 12 hr after injury, this effect was not sustained
      at 24 hr. Together, these results help to explain how minocycline has a
      deleterious effect on neuronal survival in this injury model.

PMID- 19115405
TI  - Fyn kinase is involved in oligodendroglial cell differentiation induced by
      apotransferrin.
AB  - Mechanisms that regulate oligodendroglial cell (OLGc) differentiation are the
      focus of intensive research in the field of cellular and molecular neurobiology.
      We have previously shown that the addition of apotransferrin (aTf) to primary
      OLGc cultures accelerates their differentiation and induces an increase in the
      expression of different components of the myelin cytoskeleton (CSK) such as
      actin, tubulin, and some of the microtubule-associated proteins, particularly the
      stable tubulin only peptide (STOP). Fyn protein-tyrosine kinase (Fyn kinase), a
      member of the Src family, participates in signalling pathways that regulate
      OLGs/myelin cytoskeletal reorganization. It is essential for myelin development
      in the central nervous system (CNS), and its absence results in hypomyelination.
      In the present study, we used both primary cell and N19 cell line cultures to
      investigate further the mechanisms of action involved in the accelerated
      differentiation of OLGcs induced by aTf. In particular, we were interested in
      studying the participation of Fyn kinase in the different pathways involved in
      the reorganization of the OLGc/myelin cytoskeleton. In agreement with results
      already published, we found that in OLGcs, Fyn kinase is associated with Tau and
      tubulin. Using a dominant-negative of Tau in which the Fyn-Tau-microtubules (MTs)
      interaction is blocked, we found that aTf was unable to induce OLGc morphological
      differentiation. It was also observed that aTf decreases the activated RhoA
      content in coincidence with a redistribution of actin immunoreactivity. These
      results give support to our hypothesis that Fyn kinase plays a key role in the
      differentiation process of OLGcs promoted by aTf.

PMID- 19115406
TI  - Low-intensity treadmill exercise-related changes in the rat stellate ganglion
      neurons.
AB  - Stellate ganglion (SG) represents the main sympathetic input to the heart. This
      study aimed at investigating physical exercise-related changes in the
      quantitative aspects of SG neurons in treadmill-exercised Wistar rats. By
      applying state-of-the-art design-based stereology, the SG volume, total number of
      SG neurons, mean perikaryal volume of SG neurons, and the total volume of neurons
      in the whole SG have been examined. Arterial pressure and heart rate were also
      measured at the end of the exercise period. The present study showed that a low
      intensity exercise training program caused a 12% decrease in the heart rate of
      trained rats. In contrast, there were no effects on systolic pressure, diastolic
      pressure, or mean arterial pressure. As to quantitative changes related to
      physical exercise, the main findings were a 21% increase in the fractional volume
      occupied by neurons in the SG, and an 83% increase in the mean perikaryal volume
      of SG neurons in treadmill-trained rats, which shows a remarkable neuron
      hypertrophy. It seems reasonable to infer that neuron hypertrophy may have been
      the result of a functional overload imposed on the SG neurons by initial
      posttraining sympathetic activation. From the novel stereological data we
      provide, further investigations are needed to shed light on the mechanistic
      aspect of neuron hypertrophy: what role does neuron hypertrophy play? Could
      neuron hypertrophy be assigned to the functional overload induced by physical
      exercise?

PMID- 19115407
TI  - The neuronal apoptotic death in global cerebral ischemia in gerbil: important
      role for sodium channel modulator.
AB  - Global ischemia was induced in gerbil by bilateral occlusion of the common
      carotid arteries for 5 min. Sodium ionophore monensin or sodium channel blocker
      tetrodotoxin (TTX) was administered at doses of 10 micorg/kg, i.p., 30 min before
      ischemia induction; the dose was repeated after 22 hr. Subsequently, brain
      infarct occurred, determined at 24 hr after occlusion. Large, well-demarcated
      infarcts were observed in both hemispheres, an important observation because it
      critically influences the interpretation of the data. Because nitric oxide (NO)
      production is thought to be related to ischemic neuronal damage, we examined
      increases in Ca(2+) influx, which lead to the activation of nitric oxide synthase
      (NOS). Then we evaluated the contributions of neuronal NOS, endothelial NOS, and
      inducible NOS to NO production in brain cryosections. The cytosolic release of
      apoptogenic molecules like cytochrome c and p53 were confirmed after 24 hr of
      reflow. TUNEL (terminal deoxynucleotidyl transferase dUTP nick-end labeling)
      labeling detected the apoptotic cells, which were confirmed in neuron-rich cell
      populations. After 24 hr, all the ischemic changes were amplified by monensin and
      significantly attenuated by TTX treatment. Additionally, the nesting behavior and
      histological outcomes were examined after 7 day of reflow. The neuronal damage in
      the hippocampal area and significant decrease in nesting scores were observed
      with monensin treatment and reduced by TTX pretreatment after day 7 of reflow. To
      our knowledge, this report is the first to highlight the involvement of the
      voltage-sensitive Na(+) channel in possibly regulating in part NO system and
      apoptosis in a cytochrome c-dependent manner in global ischemia in the gerbil,
      and thus warrants further investigation.

PMID- 19115408
TI  - Peripheral challenge with double-stranded RNA elicits global up-regulation of
      cytokine gene expression in the brain.
AB  - It is well established that mediators of peripheral inflammation are relayed to
      the brain and elicit sickness behavior via neuroinflammatory agents that target
      neuronal substrates. In the present study, we used double-stranded RNA (dsRNA), a
      viral replication intermediate, to mimic the acute phase of viral infection.
      C57BL/6 mice were injected intraperitoneally with 12 mg/kg of synthetic dsRNA,
      i.e., polyinosinic-polycytidylic acid (PIC). The treatment induced severe
      sickness behavior in the animals as revealed by the burrowing test performed 6 hr
      postinjection. PIC challenge also induced up-regulation of mRNA for several
      cytokines in the brain as determined by real-time quantitative RT-PCR. In all
      brain regions, i.e., the forebrain, brainstem, and cerebellum, the gene encoding
      the CXCL2 chemokine featured the most robust up-regulation over the basal level
      (saline-injected animals), followed by the genes encoding the CCL2 chemokine,
      interferon-beta (IFNbeta), interleukin-6 (IL-6), tumor necrosis factor-alpha
      (TNFalpha), and interleukin-1beta (IL-1beta). The forebrain featured the highest
      extent of up-regulation of the Ifnb gene, whereas the other genes attained the
      highest expression in the cerebellum. Most of the genes featured transient up
      regulation, with peaks occurring 3-6 hr after PIC challenge. The TNFalpha, CCL2,
      CXCL2, IFNbeta, and IL-1beta messages remained profoundly up-regulated even at 24
      hr. The expression of genes encoding inducible and neuronal nitric oxide synthase
      (NOS) in the brain was not affected by the peripheral PIC challenge. However, the
      endothelial NOS message was initially down-regulated and subsequently up
      regulated, indicating stimulation of cerebral vasculature.

PMID- 19115409
TI  - AUF1 and Hu proteins in the developing rat brain: implication in the
      proliferation and differentiation of neural progenitors.
AB  - Posttranscriptional events such as RNA stabilization are important for cell
      differentiation, but little is known about the impact of AU-rich binding proteins
      (AUBPs) on the fate of neural cells. Expression of destabilizing AUBPs such as
      AUF1 and neuronal-specific stabilizing proteins such as HuB, HuC and HuD was
      therefore analyzed in the developing central nervous system. Real-time RT-PCR
      indicated a specific developmental pattern in the postnatal cerebellum, with a
      progressive down-regulation of AUF1 from P1, whereas HuB was strongly up
      regulated at about P7. These changes were accompanied by a progressive increase
      in AUF1p45 and the disappearance of one HuB isoform from P15, suggesting
      particular roles for these AUBPs in the developing cerebellum. AUF1 was detected
      in the three main cerebellar layers, whereas Hu proteins were found only in
      postmitotic neurons. A role for Hu proteins in the early stages of neuronal
      differentiation is further supported by arrest of cell proliferation following
      induction of HuB or HuD expression in a neural stem cell line. The decrease in
      nestin expression suggest that HuD, but not HuB, favors the transition of neural
      progenitors into early neuroblasts, but other factors are most probably required
      for their full differentiation into neurons, insofar as GAP-43 was not detected
      in HuD-transfected cells. These data suggest critical roles for HuB at the very
      earliest stages of neuronal differentiation, such as cell cycle exit, and HuD
      might also be involved in the transition of neural progenitors into early
      neuroblasts. Taken together, the present results strengthen the importance of
      AUBPs in brain ontogenesis.

PMID- 19115410
TI  - Purinergic receptor activation evokes neurotrophic factor neuropeptide Y release
      from neonatal mouse olfactory epithelial slices.
AB  - One premise regarding the mechanism of injury-evoked neuroregeneration is that
      injured cells induce the release of neurotrophic factors to trigger neurogenesis.
      Extracellular purine nucleotides exert multiple neurotrophic actions in the
      central nervous system mediated via activation of purinergic receptors. However,
      whether purinergics have a neurotrophic role in the olfactory neuroepithelium has
      not been investigated. Thus, we monitored the ATP-induced release of neuropeptide
      Y (NPY), a neuropeptide that increases neuroproliferation in the olfactory
      epithelium. To visualize NPY release, slices of olfactory epithelium from
      neonatal mice were cultured on nitrocellulose paper. Immunoassays of the
      nitrocellulose demonstrated NPY immunoreactivity in regions corresponding to the
      olfactory epithelium of the nasal cavity. One hour of exposure to exogenous ATP
      (100, 500 microM) significantly increased the number of olfactory epithelium
      slices that released NPY from 25% +/- 6% to 60% +/- 7% or 71% +/- 10% (P =
      0.001). The purinergic receptor antagonists pyridoxalphosphate-6-azophenyl-2',4'
      disulfonic acid (PPADS; 25 microM) and suramin (100 microM) significantly reduced
      the number of olfactory epithelium slices exhibiting ATP-evoked NPY release to
      18% +/- 11% (P = 0.004), indicating that NPY release is mediated by activation of
      purinergic receptors. Released NPY was quantified by enzyme and
      radioimmunoassays. Exogenous ATP or UTP significantly increased the amount of NPY
      released. Overall, this study demonstrates that purinergic receptor activation
      mediates the release of neurotrophic factor NPY in the olfactory epithelium and
      provides pharmacological targets to promote regeneration of damaged olfactory
      epithelium.

PMID- 19115411
TI  - Analysis of mice with targeted deletion of AQP9 gene provides conclusive evidence
      for expression of AQP9 in neurons.
AB  - AQP9 is an aquaglyceroporin that serves important functions in peripheral organs,
      including the liver. Reflecting the lack of AQP9 knockout mice, uncertainties
      still prevail regarding the localization and roles of AQP9 in the central nervous
      system. Here we present a comprehensive analysis of AQP9 gene expression in
      brain, based on a quantitative and multipronged approach that includes the use of
      animals with targeted deletion of the AQP9 gene. We show by real-time PCR that
      AQP9 mRNA concentration in rat and mouse brain is approximately 3% and
      approximately 0.5%, respectively, of that in rat and mouse liver, the organ with
      the highest level of AQP9. By blue native gel analysis it could be demonstrated
      that the brain contains tetrameric AQP9, corresponding to the functional form of
      AQP9. The band corresponding to the AQP9 tetramer was absent in AQP9 knockout
      brain and liver. Immunocytochemistry and in situ hybridization analyses with AQP9
      knockout controls show that subpopulations of nigral neurons express AQP9 both at
      the mRNA and at the protein levels and that populations of cortical cells
      (including hilar neurons in the hippocampus) contain AQP9 mRNA but no detectable
      AQP9 immunosignal. The present data provide conclusive evidence for the presence
      of tetrameric AQP9 in brain and for the expression of AQP9 in neurons.

PMID- 19115412
TI  - Contribution of the striatum to the effects of 5-HT1A receptor stimulation in L
      DOPA-treated hemiparkinsonian rats.
AB  - Clinical and experimental studies implicate the use of serotonin (5-HT)1A
      receptor agonists for the reduction of L-3,4-dihydroxyphenylalanine (L-DOPA)
      induced dyskinesia (LID). Although raphe nuclei likely play a role in these
      antidyskinetic effects, an unexplored population of striatal 5-HT1A receptors (5
      HT1AR) may also contribute. To better characterize this mechanism, L-DOPA-primed
      hemiparkinsonian rats received the 5-HT1AR agonist +/-8-OH-DPAT (0, 0.1, 1.0
      mg/kg, i.p.) with or without cotreatment with the 5-HT1AR antagonist WAY100635
      (0.5 mg/kg, i.p.) 5 min after L-DOPA, after which abnormal involuntary movements
      (AIMs), rotations, and forelimb akinesia were quantified. To establish the
      effects of 5-HT1AR stimulation on L-DOPA-induced c-fos and preprodynorphin (PPD)
      mRNA within the dopamine-depleted striatum, immunohistochemistry and real-time
      reverse transcription polymerase chain reaction, respectively, were used.
      Finally, to determine the contribution of striatal 5-HT1AR to these effects, L
      DOPA-primed hemiparkinsonian rats received bilateral intrastriatal microinfusions
      of +/-8-OH-DPAT (0, 5, or 10 microg/side), WAY100635 (5 microg/side), or both (10
      microg + 5 microg/side) 5 min after L-DOPA, after which AIMs and rotations were
      examined. Systemic +/-8-OH-DPAT dose- and receptor-dependently attenuated L-DOPA
      mediated AIMs and improved forelimb akinesia. Striatal c-fos immunoreactivity and
      PPD mRNA ipsilateral to the lesion were strongly induced by L-DOPA, while +/-8-OH
      DPAT suppressed these effects. Finally, intrastriatal infusions of +/-8-OH-DPAT
      reduced AIMs while coinfusion of WAY100635 reversed its antidyskinetic effect.
      Collectively, these results support the hypothesis that the cellular and
      behavioral properties of 5-HT1AR agonists are conveyed in part via a population
      of functional 5-HT1AR within the striatum.

PMID- 19115413
TI  - Effect of estradiol on striatal dopamine activity of female hemiparkinsonian
      monkeys.
AB  - A higher prevalence and incidence of Parkinson's disease is observed in men, and
      beneficial motor effects of estrogens are observed in parkinsonian women. In
      rodents, an effect of estradiol on dopamine systems is documented, whereas much
      less is known in monkeys. Enkephalin was shown to exert a compensatory modulatory
      effect on the denervated dopamine nigrostriatal pathway in monkeys and in humans.
      Moreover in rodents, striatal preproenkephalin mRNA is increased by estrogen
      treatment. Hence, we investigated the responsiveness of striatal dopamine to
      estradiol in long-term ovariectomized monkeys bearing a unilateral lesion with 1
      methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) to mimic parkinsonian
      postmenopausal women. Seven ovariectomized female monkeys received a unilateral
      MPTP lesion; 4 years after ovariectomy, three received 1-month treatment with
      17beta-estradiol and the others received vehicle. The lesioned striata showed
      extensive denervation in all monkeys as measured with dopamine and metabolite
      concentrations assayed by high-performance liquid chromatography and by
      autoradiography of the dopamine transporter. The lesioned and intact striata of
      estradiol-treated monkeys had increased 3-methoxytyramine, and lesioned putamen
      increased dopamine concentrations compared with vehicle-treated monkeys.
      Estradiol treatment increased the dopamine transporter in subregions of the
      intact caudate and putamen compared with the intact striata of vehicle-treated
      monkeys, but not in the lesioned striata. Preproenkephalin mRNA levels measured
      by in situ hybridization were increased in the lesioned striata of vehicle
      treated monkeys and were not further enhanced in estradiol-treated monkeys. These
      results show that long after ovariectomy, modeling postmenopausal hormonal
      conditions, brain dopamine metabolism, and transporter are still responsive to
      estradiol.

PMID- 19115414
TI  - MRG15, a component of HAT and HDAC complexes, is essential for proliferation and
      differentiation of neural precursor cells.
AB  - Neurogenesis during development depends on the coordinated regulation of self
      renewal and differentiation of neural precursor cells (NPCs). Chromatin
      regulation is a key step in self-renewal activity and fate decision of NPCs.
      However, the molecular mechanism or mechanisms of this regulation is not fully
      understood. Here, we demonstrate for the first time that MRG15, a chromatin
      regulator, is important for proliferation and neural fate decision of NPCs.
      Neuroepithelia from Mrg15-deficient embryonic brain are much thinner than those
      from control, and apoptotic cells increase in this region. We isolated NPCs from
      Mrg15-deficient and wild-type embryonic whole brains and produced neurospheres to
      measure the self-renewal and differentiation abilities of these cells in vitro.
      Neurospheres culture from Mrg15-deficient embryo grew less efficiently than those
      from wild type. Measurement of proliferation by means of BrdU (bromodeoxyuridine)
      incorporation revealed that Mrg15-deficient NPCs have reduced proliferation
      ability and apoptotic cells do not increase during in vitro culture. The reduced
      proliferation of Mrg15-deficient NPCs most likely accounts for the thinner
      neuroepithelia in Mrg15-deficient embryonic brain. Moreover, we also demonstrate
      Mrg15-deficient NPCs are defective in differentiation into neurons in vitro. Our
      results demonstrate that MRG15 has more than one function in neurogenesis and
      defines a novel role for this chromatin regulator that integrates proliferation
      and cell-fate determination in neurogenesis during development.

PMID- 19115416
TI  - Striatal transplantation in a rodent model of multiple system atrophy: effects on
      L-Dopa response.
AB  - Progressive degeneration of striatal projection neurons is thought to account for
      the loss of L-Dopa response observed in the majority of patients with the
      parkinsonian variant of multiple system atrophy (MSA-P). Here we have
      investigated the effects of E14 embryonic striatal allografts on dopaminergic
      responsiveness in the unilateral double-lesion rat model of MSA-P by using tests
      of complex motor behavior. Both sham and graft animals showed an increase in
      apomorphine-induced rotations as well as an improvement in cylinder test
      performance following surgical intervention. In contrast, L-Dopa responsiveness
      of stepping behavior was improved only in grafted animals. The restoration of
      apomorphine-induced rotation correlated with the P-zone volume of grafts. Our
      findings indicate that transplantation of embryonic striatal grafts might, at
      least to some extent, restore responsiveness to L-Dopa in tasks of complex motor
      behavior. Therefore, striatal transplantation should be further defined
      preclinically as a possible therapeutic option for patients with MSA-P and a
      failing L-Dopa response.

PMID- 19115415
TI  - Vessel microport technique for applications in cerebrovascular research.
AB  - Cerebrovascular research suffers from a lack of reliable methods with which to
      deliver exogenous substances effectively into the central nervous system (CNS) of
      small experimental animals. Here we describe a novel vessel microport surgical
      technique for a variety of cerebrovascular applications that is reproducible and
      well tolerated in mice. The procedure is based on the insertion of a vessel
      microport into the external carotid artery for substance delivery into the CNS
      via the internal carotid artery. The method results in selective substance
      delivery into the ipsilateral hemisphere. Other novel aspects of this surgical
      technique include the ability to perform multiple injections, study of conscious
      mice well removed from surgery, and lack of occlusion of the common or internal
      carotid artery that allows carotid flow to be maintained. The feasibility of this
      technique has been validated by infusion of HIV Tat protein to induce
      permeability of the blood-brain barrier and by implantation of tumor cells to
      establish a brain metastasis model. Thus, the described vessel microport
      technique can be employed in a variety of cerebrovascular research applications.

PMID- 19115417
TI  - Adult stem cell therapies for neurological disorders: benefits beyond neuronal
      replacement?
AB  - The modest capacity of endogenous repair processes in the central nervous system
      (CNS) justifies the broad interest in the development of effective stem cell
      based therapies for neurodegenerative disorders and other acute or chronic
      lesions. Motivated by the ambitious expectation to achieve functional neuronal
      replacement, several studies have already evidenced a potential benefit of stem
      cell grafts in animal models of human disorders. Nevertheless, growing evidence
      suggests that the effects orchestrated by stem cells, in most experimental cases,
      are not necessarily associated with the generation of new neurons. This
      hypothesis correlates with the versatile properties of adult and embryonic stem
      cells. When introduced into the lesioned CNS, nondifferentiated stem cells can
      have a positive influence through intrinsic neuroprotective capacities related to
      the production of neurotrophic factors, stimulation of endogenous neurogenesis,
      and modulation of neuroinflammation. Stem cells are also endowed with a
      multipotent differentiation profile, suggesting that a positive outcome could
      result from the replacement of nonneuronal cell types, in particular astrocytes
      and oligodendrocytes. Focusing on adult stem cells, this Review aims at
      summarizing experimental observations supporting the concept that, in cell-based
      therapies, stem cells operate not through a unidirectional mechanism (e.g.,
      generating neurons) but rather as cellular mediators of a multitude of biological
      activities that could provide a favorable outcome for diverse nervous disorders.

PMID- 19115418
TI  - In vivo infusion of UTP and uridine to the deafened guinea pig inner ear: effects
      on response thresholds and neural survival.
AB  - Nucleotides and nucleosides are known to function as neurotransmitters and
      neuromodulators but have recently been shown to have a trophic effect on neurons.
      It has previously been shown, in an animal model for cochlear implants, that
      local infusion of neurotrophic factors intervenes with the degenerative processes
      occurring after deafening and protects the auditory spiral ganglion neurons so
      that electrical responsiveness is maintained. Here we test the hypothesis that
      nucleosides and nucleotides have a similar effect on the acutely damaged inner
      ear. Pigmented guinea pigs received a cochlear implant electrode for measuring
      electrically evoked auditory brainstem responses and a miniosmotic pump for
      delivering drugs directly to the cochlea. The animals were deafened by a 48-hr
      infusion with 10% neomycin, followed by 23 days of treatment with primarily UTP,
      uridine nucleotides, or as control artificial perilymph. Electrically evoked
      responses were measured weekly, and at the end of the experiment the cochleae
      were collected and processed for morphological analysis and spiral ganglion
      neuron counting. Both UTP- and uridine-treated groups showed significantly better
      response after 23 days of treatment compared with the control group. The
      densities of spiral ganglion neuron were significantly higher for both treated
      groups compared with the control group treated with artificial perilymph. The
      results demonstrate that UTP and uridine rescue auditory neurons and suggest that
      drugs acting on purinoceptors could be of clinical importance.

PMID- 19115419
TI  - Hemorrhagic stroke associated with antidepressant use in patients with
      depression: does degree of serotonin reuptake inhibition matter?
AB  - OBJECTIVE: This study aimed to determine whether the degree of serotonin (5-HT)
      reuptake inhibition affects risk of hemorrhagic stroke associated with
      antidepressant use in patients with depression. METHOD: A population-based,
      nested case-control study was performed using a managed care medical claims
      database. Ninety two depressed patients with a diagnosis of hemorrhagic stroke
      were identified and matched with 552 controls by age, sex, and year of index date
      of depression (IDD). Diagnoses of depression, hemorrhagic stroke, and other
      medical comorbidities were identified using ICD-9 codes. Antidepressants were
      classified as high, medium, or low reuptake inhibition based on their affinities
      for the 5-HT reuptake transporter, determined using their respective equilibrium
      dissociation constants (K(D); high: K(D) < 1 nM; medium: 1 <or= K(D) < 10 nM;
      low: K(D) >or= 10 nM). Conditional logistic regression analysis was performed to
      estimate the crude and adjusted odds ratios (ORs) with 95% confidence intervals
      (CIs) of the risk of hemorrhagic stroke. RESULTS: Compared to non-users of
      antidepressants, risk of hemorrhagic stroke did not significantly differ between
      patients who had ever used antidepressants with high (OR = 0.82; 95% CI = 0.44
      1.55), medium (OR = 0.93; 95% CI = 0.37-2.31), or low (OR = 0.38; 95% CI = 0.11
      1.41) 5-HTT inhibition. CONCLUSION: Risk of hemorrhagic stroke associated with
      antidepressant use may not be related to an antidepressant's degree of 5-HT
      reuptake inhibition. Given the limitations of this study, additional studies are
      needed to confirm these findings.

PMID- 19115420
TI  - A novel Global Assessment Scale for Wilson's Disease (GAS for WD).
AB  - Wilson's disease (WD) is an inherited disorder of copper metabolism. Despite
      being treatable, patients with WD suffer severe disabilities due to delay in
      initiation and difficulty in monitoring treatment. We propose a two tier, Global
      Assessment Scale for Wilson's Disease (GAS for WD) that grades the multisystemic
      manifestations of the disease. Tier 1 scores the global disability in four
      domains: Liver, Cognition and behavior, Motor, and Osseomuscular. Tier 2 is
      multidimensional scale for a fine grained evaluation of the neurological
      dysfunction. We prospectively validated this scale in 30 patients with WD. Both
      tiers had a high inter-rater reliability (Intraclass correlation coefficient ICC
      (A, 2) = 0.96-1.0). Tier 2 items were internally consistent (Cronbach's alpha =
      0.89) and factorial analysis showed that 90.3% of the Tier 2 total score variance
      was determined by seven factors. Scores of both tiers were commensurate with the
      disease burden as assessed by standard disability scales (Child Pugh, UPDRS, SS3,
      and CGI) and satisfied criteria for validity. Longitudinal follow-up over 1.5
      years showed that the scale was sensitive to clinical change. This suggests that
      GAS for WD is a practical tool with potential applications in management of
      patients, and in testing and comparison of treatment regimens.

PMID- 19115421
TI  - Alcohol consumption among Canadians taking benzodiazepines and related drugs.
AB  - PURPOSE: Benzodiazepines and related drugs (BZDs) are widely used for the
      treatment of anxiety, insomnia and other conditions. The combination of BZDs with
      alcohol increases risk for oversedation, abuse, dependence and accidents. This
      study examines drinking behaviour among Canadians taking BZDs. METHODS: We use
      data from cycle 1.2 of the Canadian Community Health Survey, a large (n = 36,984)
      population survey conducted in 2002 by Statistics Canada. We use bivariate
      methods and logistic regression to test the independent association between BZD
      use and 2 levels of recent drinking in the general population, and then examine
      associations between drinking and sociodemographic factors within the group of
      BZD users. RESULTS: Any drinking and heavy drinking are less common among users
      of BZDs than among other respondents, but these differences are small (any
      drinking, OR = 0.77, p = 0.02; heavy drinking, OR = 0.81, p = 0.13) when
      differences in respondent characteristics are controlled statistically. Among BZD
      users, any drinking is associated with male sex, younger age and not meeting
      criteria for a past-year anxiety disorder. Heavy drinking is associated only with
      younger age. CONCLUSIONS: Heavy alcohol use is uncommon among users of BZDs, and
      the combination of alcohol and BZD use is rare in the general population.
      Differences between BZD users and others are not large when other factors are
      taken into account, however, which may call into question the effectiveness of
      physician and pharmacist warnings against this combination. People treated for an
      anxiety disorder with BZDs may be less likely to use alcohol than those taking
      them for other indications.

PMID- 19115422
TI  - CD133+ liver cancer stem cells from methionine adenosyl transferase 1A-deficient
      mice demonstrate resistance to transforming growth factor (TGF)-beta-induced
      apoptosis.
AB  - Methionine adenosyltransferase (MAT) is an essential enzyme required for S
      adenosylmethionine biosynthesis. Hepatic MAT activity falls during chronic liver
      injury, and mice lacking Mat1a develop spontaneous hepatocellular carcinoma by 18
      months. We have previously demonstrated that CD133(+)CD45(-) oval cells isolated
      from 16-month-old Mat1a(-/-) mice represent a liver cancer stem cell population.
      The transforming growth factor beta (TGF-beta) pathway constitutes a central
      signaling network in proliferation, apoptosis, and tumorigenesis. In this study,
      we tested the response of tumorigenic liver stem cells to TGF-beta. CD133(+)CD45(
      ) oval cells were isolated from premalignant 16-month-old Mat1a(-/-) mice by flow
      cytometry and expanded as five clone lines derived from a single cell. All clone
      lines demonstrated expression of both hepatocyte and cholangiocyte markers and
      maintained a small population (0.5% to 2%) of CD133(+) cells in vitro, and three
      of five clone lines produced tumors. Although TGF-beta1 inhibited cell growth
      equally in CD133(-) and CD133(+) cells from each clone line, the CD133(+)
      population demonstrated significant resistance to TGF-beta-induced apoptosis
      compared with CD133(-) cells. Furthermore, CD133(+) cells demonstrated a
      substantial increase in mitogen-activated protein kinase (MAPK) pathway
      activation, as demonstrated by phosphorylated extracellular signal-regulated
      kinase levels before and after TGF-beta stimulation. MAPK inhibition using
      mitogen-activated protein kinase kinase 1 (MEK1) inhibitor PD98059 led to a
      significant increase in TGF-beta-induced apoptosis in CD133(+) cells. Conversely,
      a constitutively active form of MEK1 blocked the apoptotic effects of TGF-beta in
      CD133(-) cells. CONCLUSION: CD133(+) liver cancer stem cells exhibit relative
      resistance to TGF-beta-induced apoptosis. One mechanism of resistance to TGF-beta
      induced apoptosis in CD133(+) cancer stem cells is an activated mitogen-activated
      protein kinase/extracellular signal-regulated kinase pathway.

PMID- 19115423
TI  - Cognitive-behavioural, pharmacological and psychosocial predictors of outcome
      during tapered discontinuation of benzodiazepine.
AB  - Eighty-six participants wishing to stop benzodiazepine and who met DSM-IV
      (Diagnostic and Statistical Manual of Mental Disorders, 4th ed. American
      Psychological Association, 1994) criteria for anxiety disorder or insomnia were
      assessed pre- and post-taper on clinical, pharmacological and psychosocial
      measures. An initial cohort of 41 participants received treatment as usual (taper
      only) plus physician counselling in the same clinic setting. A second cohort of
      45 participants were randomly allocated to group cognitive-behavioural therapy
      (CBT) plus taper, or group support (GS) plus taper. At 3 months follow-up, the
      outcomes in both the CBT and the GS subgroups were equivalent. Intention to treat
      analysis revealed a slight advantage to the CBT over the GS group and the CBT
      group showed higher self-efficacy post-taper.Over all 86 participants, a high
      baseline level of psychological distress, anxiety and dosage predicted a poor
      outcome, but increase in self-efficacy contributed to a successful outcome
      particularly in those with initially poor baseline predictors. Although there was
      a decrease in positive affect during preliminary stages of tapered
      discontinuation compared to baseline, there was no significant overall increase
      in negative affect.

PMID- 19115424
TI  - Obsessional beliefs, compulsive behaviours and symptom severity: their evolution
      and interrelation over stages of treatment.
AB  - The current study reports a case series examining (1) the variation in strength
      of obsessional doubt and belief in consequences of the doubt; and (2) the
      interaction between these cognitive components and symptom measures of duration
      and severity of obsessive-compulsive disorder (OCD), over 24 weeks of cognitive
      behaviour therapy. Eight participants diagnosed with OCD, four with contamination
      related rituals and four with checking behaviours, were selected on the basis of
      the Yale-Brown obsessive-compulsive scale (Y-BOCS) and Padua ratings. All
      participants completed daily diaries measuring strength of principal obsessional
      doubt (0-100), strength of belief in consequences of the doubt (0-100) and the
      duration of the compulsive rituals throughout the 24 weeks of therapy. Severity
      of symptomatology was measured pre- and post-treatment using the Y-BOCS. Change
      in all measures was analysed over time following the procedure outlined by
      Storchheim and O'Mahoney (2006). Results showed that decrease in belief in
      secondary consequences is always accompanied by a decrease in strength of
      obsessions, but the converse does not hold. Furthermore, change in OCD
      symptomatology may precede cognitive changes.

PMID- 19115425
TI  - Patients' explanations for depression: a factor analytic study.
AB  - OBJECTIVES: Previous questionnaire studies have attempted to explore the factor
      structure of lay beliefs about the causes of depression. These studies have
      tended to either fail to sample the full range of possible causal explanations or
      extract too many factors, thereby producing complex solutions. The main objective
      of the present study was to obtain a more complete and robust factor structure of
      lay theories of depression while more adequately sampling from the full range of
      hypothesized causes of depression. A second objective of the study was to explore
      the relationship between respondents' explanations for depression and their
      perceptions of the helpfulness of different treatments received. METHOD AND
      DESIGN: A 77-item questionnaire comprising possible reasons for 'why a person
      might get depressed' was mailed out to members of a large self-help organization.
      Also included was a short questionnaire inviting respondents to note treatments
      received and their perceptions of the helpfulness of these treatments. Data from
      the 77-item questionnaire were subjected to a principal components analysis.
      RESULTS: The reasons rated as most important causes of depression related to
      recent bereavement, imbalance in brain chemistry and having suffered sexual
      assault/abuse. The data were best described by a two-factor solution, with the
      first factor clearly representing stress and the second factor depressogenic
      beliefs, the latter corresponding to a cognitive-behavioural formulation of
      depression aetiology. The two scales thus derived did not, however, correspond
      substantially with rated helpfulness for different treatments received.
      CONCLUSIONS: The factor structure obtained was in contrast to more complex models
      from previous studies, comprising two factors. It is likely to be more robust and
      meaningful. It accords with previous research on lay theories of depression,
      which highlight 'stress' as a key cause for depression. Possible limitations in
      the study are discussed, and it is suggested that using the questionnaire with
      more recently depressed people might yield clearer findings in relation to
      perceptions of treatment helpfulness.

PMID- 19115426
TI  - Treatment of child anxiety: an exploratory study of the role of maternal anxiety
      and behaviours in treatment outcome.
AB  - Anxiety disorders are common among parents of anxious children and have been
      found to impede child treatment outcomes, yet it is unclear whether it is
      parental anxiety that needs to be targeted in therapy or associated parental
      behaviours. Twenty-two children (6-12 years) with a current anxiety disorder and
      their mothers received cognitive-behavioural treatment (CBT) for child anxiety.
      In addition, of the 12 mothers who met criteria for a current anxiety disorder, 6
      received CBT for their own disorder. Assessments were made of the mother-child
      interaction. The main findings were: (1) children did less well from treatment
      where their mothers had a current anxiety disorder; (2) treatment of maternal
      anxiety disorder did not improve child treatment outcome; and (3) maternal
      overinvolvement and expression of fear was associated with child treatment
      outcome. The results suggest that in the context of maternal anxiety disorder,
      child treatment outcome may be improved by specifically targeting parenting
      behaviours.

PMID- 19115427
TI  - The voice and you: development and psychometric evaluation of a measure of
      relationships with voices.
AB  - The experience of hearing voices has recently been conceptualized within a
      relational framework. Birtchnell's Relating Theory offers a framework capable of
      exploring the power and intimacy within the relationship between the hearer and
      the voice. However, measures of relationships with voices derived from the
      theory, such as the Hearer to Voice (HTV) and Voice to Hearer (VTH) by Vaughan
      and Fowler, have lacked robust psychometric properties. Data were available from
      71 participants who completed the HTV and VTH, and analysis of these data
      generated a new 29-item measure, the Voice and You (VAY), capable of assessing
      the 'interrelating' between the hearer and the voice. The VAY was completed by a
      further 30 participants and was found to be internally consistent, stable over
      time and associated with other measures of the voice-hearing experience. The VAY
      offers a psychometrically stable measure of the relationship between the hearer
      and the voice. It may be used as an adjunct to the clinical interview and/or a
      measure of outcome.

PMID- 19115428
TI  - The use of mindfulness in obsessive compulsive disorder: suggestions for its
      application and integration in existing treatment.
AB  - Treatment for obsessive-compulsive disorder (OCD) is a standard activity of
      psychologists, particularly those in Community Mental Health Teams (CMHT). In
      2005, NICE published guidelines recommending Cognitive Behavioural Therapy (CBT)
      with Exposure and Response Prevention (ER-P) as the evidence-based psychological
      treatments of choice. In recent years there have been significant developments
      within cognitive behavioural theory, including what has been referred to as the
      'Third Wave'. This paper explores the contribution of mindfulness; a practice
      that has previously been integrated into other CBT models of treatment, to
      cognitive interventions in OCD, suggesting that in complements both CBT and ER
      However it had previously been suggested by Freeston that mindfulness may prevent
      successful ER-P by becoming a neutralising technique. Examples of the application
      of a mindfulness-based approach are explored (MOCD), including reference to an
      OCD group run by the author, and areas of potential overlap are identified, in
      particular thought-action Fusion. It is concluded that if applied properly,
      mindfulness not only complements traditional CBT interventions, but could also
      increase their efficacy and perhaps prevent relapse.

PMID- 19115429
TI  - Effectiveness of bibliotherapy self-help for depression with varying levels of
      telephone helpline support.
AB  - The effectiveness of a cognitive behavioural bibliotherapy self-help package,
      with varied levels of telephone support, delivered through a mental health
      telephone service was examined with 84 mildly to moderately depressed adults. The
      study compared the changes in depressive symptoms of three groups: control, self
      help with minimal contact and self-help with telephone assistance. Both the
      minimal contact and the assisted self-help groups had significant reductions in
      their levels of depression compared with the control group. Treatment gains were
      maintained at a 1-month follow-up. The potential of self-help resources such as
      this to be successfully disseminated and delivered through a national mental
      health telephone information service is discussed.

PMID- 19115430
TI  - Changing relationship with voices: new therapeutic perspectives for treating
      hallucinations.
AB  - A growing body of research on verbal hallucinations shows the importance of
      beliefs about and relationships with the voices for their pathological course. In
      particular, beliefs about the omnipotence of the voices and the need to control
      them, and relationships with them that involve efforts to resist or fight them,
      have shown themselves to be more pathogenic than effective. Likewise, treatments
      aimed at eliminating the voices, be they based on medication or 'traditional'
      cognitive-behavioural therapy, have not always been successful. A series of
      strategies focused on changing relationships with the voices instead of trying to
      eliminate them-including mindfulness, acceptance, experiential role plays and re
      authoring lives-is emerging as a new perspective for the treatment of
      hallucinations. All of these strategies are based on the person, not on the
      syndrome, which also represents a new conception of the problem, in a
      phenomenological-social perspective, alternative to the predominant medical
      conception.

PMID- 19115431
TI  - The relation of anger to disgust: the potential role of coupled emotions within
      eating pathology.
AB  - OBJECTIVE: difficulties with anger and disgust have been highlighted within
      females with eating pathology (FEP). However, research has not investigated
      whether FEP experience greater levels of anger compared to controls or how these
      two emotions may interact in FEP. It was predicted that FEP would show
      significantly higher levels of state anger and this would also lead to a
      significant increase in disgust for FEP. METHOD: the experimental group (n = 25)
      had significant levels of eating pathology. Data from the State-Trait Anger
      Expression Inventory-2 and a disgust measure was collected before and after the
      induction of an angry state. RESULTS: the bulimic group, in comparison to normal
      controls, demonstrated a significant increase in the state anger scores at time 2
      and on the Disgust Sensitivity Scale. CONCLUSION: the findings demonstrate that
      the emotions of anger and disgust may be 'coupled', and disgust may be used to
      manage the 'egodystonic' emotion of anger in people with eating pathology.

PMID- 19115432
TI  - Danger-early maladaptive schemas at work!: The role of early maladaptive schemas
      in career choice and the development of occupational stress in health workers.
AB  - The schema-focused model of occupational stress and work dysfunctions (Bamber &
      Price, 2006; Bamber, 2006) hypothesizes that individuals with EMS (unconsciously)
      gravitate toward occupations with similar dynamics and structures to the toxic
      early environments and relationships that created them. They subsequently re
      enact these EMS and their associated maladaptive coping styles in the workplace.
      For most individuals, this results in 'schema healing', but for some individuals
      with more rigid and severe EMS, schema healing is not achieved and the structures
      and relationships of the workplace, together with the utilization of maladaptive
      coping styles, serve to perpetuate their EMS. The model hypothesizes that it is
      these individuals who are most vulnerable to developing occupational stress
      syndromesTo date, this model has been subjected to very little empirical
      investigation, so the main aim of this study was to address this gap in the
      literature by testing out some of its main assumptions and to provide empirical
      data, which would either support or reject the model using a population of health
      workers. Specifically, it was hypothesized that 'occupation-specific' EMS would
      be found in health workers from a range of different healthcare professions. It
      was also hypothesized that the presence of higher levels of EMS would be
      predictive of raised levels of occupational stress, psychiatric caseness and
      increased sickness absence in those individuals.A cross-sectional study design
      was employed and a total of 249 staff working within a NHS Trust, belonging to
      one of five occupational groups (medical doctors, nurses, clinical psychologists,
      IT staff and managers), participated in the study. All participants completed the
      Young Schema Questionnaire-Short Form (Young, 1998); the Maslach Burnout
      Inventory-Human Services Form (Maslach & Jackson, 1981), and the General Health
      Questionnaire-28-item version (Goldberg, 1978). A demographic questionnaire and
      sickness absence data was also collected. The results of a between groups
      analysis of variance and further post hoc statistical analyses identified a
      number of occupation specific EMS. Also, the results of a series of multiple
      linear regression analyses indicated the presence of some EMS to be predictive of
      higher levels of burnout, psychiatric caseness and sickness absence in health
      workers. In conclusion, the findings of this study provide empirical support for
      the schema-focused model of occupational stress and work dysfunctions (Bamber &
      Price, 2006; Bamber, 2006), and it appears that the existence of underlying EMS
      may constitute a predisposing vulnerability factor to developing occupational
      stress.

PMID- 19115433
TI  - Compassionate mind training with people who hear malevolent voices: a case series
      report.
AB  - This paper presents a series of case studies to explore the understanding,
      acceptance and value of compassionate mind training (CMT) with psychotic voice
      hearers. We were interested in the degree to which such people are able to access
      and feel the positive emotions of 'warmth' and 'contentment' to become more self
      compassionate. We also explored how CMT affected participants' hostile voices,
      their levels of anxiety, depression, paranoia and self-criticism. Participants
      were invited to offer suggestions for tailoring this approach for voice hearers.
      Results showed decreases for all participants in depression, psychoticism,
      anxiety, paranoia, Obsessive-Compulsive Disorder and interpersonal sensitivity.
      All participants' auditory hallucinations became less malevolent, less
      persecuting and more reassuring.

PMID- 19115434
TI  - Cross-cultural analysis of quality of life and mental health.

PMID- 19115435
TI  - Short forms of subjective quality of life assessments from cross-cultural studies
      for use in surveys with different populations.
AB  - Among several advances in quality of life (QOL) assessment development, such as
      cross-cultural comparability of measurements, inclusion of more specific target
      populations, and assessment on different levels of QOL generality, economy of
      measurement has become of increasing importance. As a consequence, construction
      of short forms and indices of original measures is common in QOL assessment
      development. The present paper puts special emphasis upon the issue of shortening
      measures and developing short forms in QOL assessment in relation to this
      development. Some basic principles and procedures of short-form development in
      general are outlined, and selected prominent examples of short-form development
      as applied to QOL assessment are described.

PMID- 19115436
TI  - Mental health of children and adolescents in 12 European countries-results from
      the European KIDSCREEN study.
AB  - Within the European Screening for and Promotion of Health-Related Quality of Life
      in Children and Adolescents-A European Public Health Perspective (KIDSCREEN)
      Study, emotional well-being and behaviour was examined in national representative
      samples of 22 000 children and adolescents aged 8 to 18.The proportion of
      children and adolescents showing signs of mental health problems (Strengths and
      Difficulties Questionnaire-SDQ) varied across countries and socio-demographic and
      socio-economic subgroups. Risk factors examined included adverse family climate,
      low socio-economic status, poor social support and decreased mental well-being of
      the parents. When several risk factors occur simultaneously, the prevalence of
      mental health problems increases markedly. Children and adolescents with mental
      health problems display distinctly impaired health-related quality of life
      (KIDSCREEN-10).Cross-cultural differences in the observed patterns of mental
      health problems were discussed. High-risk groups are cross-culturally
      characterized by poor social support and mental distress of parents.
      Strengthening social and familial resources should be a key objective, both in
      prevention and in interventions.

PMID- 19115437
TI  - Psycho-social determinants of quality of life in children and adolescents with
      haemophilia-a cross-cultural approach.
AB  - Quality of life (QoL) of children with chronic conditions has received increasing
      attention in recent years. While frequent paediatric health conditions and life
      threatening conditions are in the foreground, QoL of children with rare diseases
      such as haemophilia is scarce. While haemophilia-specific instruments to assess
      QoL in children have been developed, cross-cultural comparison of QoL and its
      determinants has not been addressed so far. QoL and potential psychosocial
      determinants such as coping were assessed in 298 paediatric haemophilia patients
      from six European countries demonstrating significant differences in QoL between
      countries. Results indicated that psychosocial predictors varied across
      countries, although life satisfaction and social support explained the highest
      proportion of variance and, moreover, superseded clinical characteristics. These
      findings suggest that intervention programmes should be geared towards enhancing
      psychosocial resources in children and adolescents with haemophilia.

PMID- 19115438
TI  - DISABKIDS smiley questionnaire: the TAKE 6 assisted health-related quality of
      life measure for 4 to 7-year-olds.
AB  - The DISABKIDS Smiley TAKE 6 was developed to meet the need for a research
      instrument to measure the health-related quality of life (HrQoL) of children 4-7
      years old. TAKE 6 is a European generic assisted-report questionnaire with a
      proxy version. The items of TAKE 6, scored using a five-point Likert scale, cover
      a single HrQoL domain. Child and parent focus groups identified the statements
      which, following a European pilot study, were reduced to six items. A field study
      of 435 children with a chronic disease in seven European countries revealed that
      the questionnaire had good reliability (inter-class correlation 0.69), had
      convergent validity with the KINDL-R (child quality of life questionnaire
      revised) (rho 0.60) and satisfactory construct validity showing separation
      between severity and different medical conditions. The questionnaire was
      understandable by young children and could be completed within two minutes.

PMID- 19115439
TI  - Evaluation of the mental health continuum-short form (MHC-SF) in setswana
      speaking South Africans.
AB  - A continuous assessment and a categorical diagnosis of the presence of mental
      health, described as flourishing, and the absence of mental health, characterized
      as languishing, is applied to a random sample of 1050 Setswana-speaking adults in
      the Northwest province of South Africa. Factor analysis revealed that the mental
      health continuum-short form (MHC-SF) replicated the three-factor structure of
      emotional, psychological and social well-being found in US samples. The internal
      reliability of the overall MHC-SF Scale was 0.74. The total score on the MHC-SF
      correlated 0.52 with a measure of positive affect, between 0.35 and 0.40 with
      measures of generalized self-efficacy and satisfaction with life, and between
      0.30 and 0.35 with measures of coping strategies, sense of coherence, and
      community collective self-efficacy. The total score on the MHC-SF correlated 
      0.22 with the total score on the General Health Questionnaire. Criteria for the
      categorical diagnosis were applied, and findings revealed that 20% were
      flourishing, 67.8% were moderately mentally healthy, and 12.2% were languishing.
      Confirmatory factor analysis supported the hypothesized two-continua model of
      mental health and mental illness found in the USA.

PMID- 19115440
TI  - Demographic and psychosocial correlates of quality of life in the elderly from a
      cross-cultural perspective.
AB  - We compared the quality of life (QOL) of older adults in a post-communist country
      (the Czech Republic) with those living in traditional western democracies. The
      sample comprised 1981 respondents aged 60+ (from 60 to 99). The subjective QOL
      was measured using the WHOQOL-BREF and the add-on module for older adults, the
      WHOQOL-OLD. The findings showed higher score of depressive symptoms measured by
      the GDS scale and lower QOL in Czech sample as compared to other centres.
      Analyses of factors related to QOL of older adults showed similar patterns for
      the Czech sample and other centres with depression emerging as the strongest
      determinant of reduced QOL Findings also underline that subjective quality of
      life measurement reflects cross-country differences in accordance with objective
      indicators of national prosperity.

PMID- 19115441
TI  - Emotion regulation as mediator of treatment outcome in therapy for deliberate
      self-harm.
AB  - This study presents the outcomes of mediator analyses as part of a randomized
      controlled trial of Cognitive-Behavioural Therapy (CBT) for young people who
      engage in deliberate self-harm (DSH). The study involved 90 people, aged 15-35
      years, who were randomly assigned to CBT in addition to treatment as usual or to
      treatment as usual only. The findings showed that changes in DSH were partially
      mediated by changes in emotion-regulation difficulties, particularly difficulties
      with impulse control and goal-directed behaviours. In addition, the potential
      mediating role of symptoms of depression, anxiety and suicidal cognitions was
      examined. Although the CBT intervention significantly reduced depression, anxiety
      and suicidal cognitions, these measures of symptom severity did not play a
      mediating role. These findings suggest that interventions for DSH should not
      primarily focus on mental disorders associated with DSH, but should be DSH
      specific and should target specific emotion-regulation difficulties.

PMID- 19115442
TI  - Intrusive images in grief: an exploratory study.
AB  - The relevance of intrusive mental imagery to the understanding and treatment of
      psychological disorders is increasingly acknowledged. Little research has been
      done on intrusive imagery in grief. Using a sample of 131 mourners, recruited
      from professional and lay mental health care workers, the current study examined
      the frequency and correlates of four specific intrusive images: (a) positive
      intrusive memories of the lost person; (b) intrusive images of the death event;
      (c) re-enactment fantasies; and (d) negative images of the future. Findings
      revealed that these intrusions were common and that the occurrence of these
      intrusions hardly varied across subgroups of mourners. All four intrusions were
      correlated with the severity of complicated grief symptoms, and intrusions (b),
      (c) and (d) were also correlated with the severity of symptoms of depression and
      anxiety. Findings have potential theoretical and clinical implications and
      indicate that a more comprehensive study of intrusions among bereaved people is
      warranted.

PMID- 19115444
TI  - Is therapist alliance or whole group cohesion more influential in group
      psychotherapy outcomes?
AB  - This study examined the differential ability of early in treatment measures of
      therapeutic alliance (Working Alliance Inventory), group cohesion (California
      Psychotherapy Alliance Scale for Group) and group climate (Group Climate
      Questionnaire) to predict outcome in a 16-session dynamic group psychotherapy for
      adults with major depression. Six successful therapy groups with 30 patients
      receiving psychodynamic group therapy were studied. Patient perceptions of the
      therapist alliance was not related to outcome, however, perceptions of levels of
      conflict and group members' ability to work actively and purposefully in
      treatment did predict outcome. Future research should further investigate how
      patients' perceptions of the whole group influence their clinical improvement.

PMID- 19115443
TI  - Inferential confusion, obsessive beliefs and obsessive-compulsive symptoms: a
      multidimensional investigation of cognitive domains.
AB  - Generally, research into the relationship between cognitive domains and obsessive
      compulsive symptoms involves the use of scales that are highly intercorrelated
      with each other. The current study investigates the relationship between
      cognitive constructs and obsessive-compulsive symptoms using the item set of the
      Obsessive Beliefs Questionnaire and the Inferential Confusion Questionnaire. In
      order to create constructs that would not be excessively correlated with each
      other, factor scores were used to investigate the relationship between cognitive
      domains and obsessive-compulsive symptoms. Factor analysis followed by oblique
      rotation resulted in four moderately correlated cognitive constructs
      (importance/control of thoughts, inferential confusion/threat estimation,
      perfectionism/certainty and responsibility for preventing harm). With the
      exception of responsibility for preventing harm, the cognitive constructs under
      investigation were quite strongly related to obsessive-compulsive symptoms. In
      particular, hierarchical regression revealed the construct inferential
      confusion/threat estimation to be a global and strong predictor of obsessive
      compulsive symptoms, followed by the constructs of perfectionism/certainty and
      the construct importance/control. Responsibility for preventing harm acted to be
      a negative predictor of obsessive-compulsive symptoms. It is concluded that the
      construct of inferential confusion acts as a more powerful predictor of obsessive
      compulsive symptoms than any specific obsessive belief

PMID- 19115445
TI  - Therapist technique and patient defensive functioning in ultra-brief
      psychodynamic psychotherapy: a Lag sequential analysis.
AB  - This study examined the association between therapist interventions, including
      interpretations, and patient defensive functioning. The first session of 32 (n =
      32) Brief Psychodynamic Interventions were rated for therapist interventions and
      patient defensive functioning. Lag sequential analysis was used to determine if
      (a) there are organized sequences of therapist interventions; (b) there are
      predictable sequences in the patients' level of defensive functioning; (c) there
      are sequences of therapist interventions leading to change in the patients'
      defensive functioning; and (d) there are levels of patient defensive functioning
      leading to organized therapist response. Results suggested that there are
      organized sequences in the therapists' interventions and that patient in-session
      defensive functioning is relatively stable. However, no chain of therapist
      interventions led to a predictable response in the patients' defensive
      functioning or vice versa.

PMID- 19115446
TI  - Psychologists' judgements of diagnostic activities: deviations from a theoretical
      model.
AB  - In this article, we describe an investigation into the diagnostic activities of
      practicing clinical psychologists. Two questionnaires were filled in by 313
      psychologists. One group of psychologists (N = 175) judged the necessity of
      diagnostic activities; the other group (N = 138) selected the activities they
      would actually perform. Results showed that more participants thought that
      diagnostic activities were necessary than there were participants who intended to
      actually perform those activities. Causal analysis, by generating and testing
      diagnostic hypotheses to form an integrated client model with an explanation for
      the problem, was judged least necessary and would not be performed. We conclude
      that a discrepancy exists between the number and types of activities
      psychologists judged to be necessary and they intend to actually perform. The
      lack of attention for causal analysis is remarkable as causal explanations are
      crucial to effective treatment planning.

PMID- 19115447
TI  - Age differences in temperament, character and depressive mood: a cross-sectional
      study.
AB  - INTRODUCTION: This study explores the effect of age on mean-levels of the
      personality traits defined in Cloninger's personality taxonomy, and investigates
      the relevance of personality traits for predicting depression levels in adults
      aged 18 to 94 years. METHOD: We divided our sample (466 participants) into four
      age groups (young adult, adult, mature adult and elderly). Personality was
      measured using the Temperament and Character Inventory, and depression was
      assessed using the Hospital Anxiety and Depression Scale. RESULTS: Analysis of
      variance showed mean-level changes for all the personality traits except Self-D.
      Post hoc analyses revealed a decrease in the level of novelty seeking with age
      and an increase in the level of self-transcendence for the two oldest age groups.
      Reward dependence was highest among the youngest participants, whereas harm
      avoidance was highest for both the youngest and the oldest age groups. Depression
      correlated positively with harm avoidance and age but negatively with self
      transcendence. DISCUSSION: Impulsiveness, curiosity and social dependency
      decrease with age, whereas spirituality increases. Young and elderly adults are
      more fearful and socially inhibited. Harm avoidance and self-transcendence are
      the most relevant personality traits for predicting levels of depression.

PMID- 19115448
TI  - Memories of early attachment: the use of PBI as a predictor of outcome in Pesso
      Boyden System Psychomotor (PBSP) group therapy, Cognitive-Behavioural Group
      Therapy (CBGT), Individual Cognitive-Behavioural Therapy (CBT) and Individual
      Treatment As Usual (TAU) with adult out-patients.
AB  - OBJECTIVE: To examine the predictive validity of the Parental Bonding Instrument
      (PBI) for outcome in individual and group psychotherapy. METHOD: Data from four
      different clinical trials were combined, yielding a total of 105 patients. After
      controlling for gender, age and initial symptomatic distress, the predictive
      validity of the PBI subscales was investigated using the symptom checklist-90
      revised (SCL-90-R) and inventory of interpersonal problems-64 (IIP-64) at
      termination as dependent measures in each treatment condition using separate
      hierarchical multiple regression analyses. RESULTS: Using the SCL-90-R at
      termination as dependent measure, reports of higher paternal and maternal care
      were related to a worse outcome in the Pesso-Boyden System Psychomotor condition,
      whereas reports of higher paternal care were related to a better outcome in the
      Cognitive-Behavioural Therapy condition. Also, higher maternal protection was
      related to a better outcome in the Cognitive-Behavioral Group condition. Using
      the IIP-64 at termination as dependent measure, reports of higher paternal
      protection were related to a better outcome in the Treatment As Usual condition.
      DISCUSSION: The study shows that the PBI may function as a clinical predictor for
      treatment response, although the results were somewhat contrary to previous
      reportings. Future studies should contrast and investigate possible differences
      between individual and group treatments further, as well as more clearly defined
      diagnostic groups. Clinical implications are presented.

PMID- 19115449
TI  - Improving psychotherapy outcome: the use of immediate electronic feedback and
      revised clinical support tools.
AB  - The benefits of psychotherapy have been well documented; however, 5-10% of
      clients worsen while in treatment and another minority shows no response. The
      effects of feedback timing (delayed or immediate) and type (progress feedback and
      Clinical Support Tool [CST] feedback), aimed at reducing deterioration and
      improving outcomes, were examined in a sample of 1101 clients whose outcome was
      contrasted across experimental groups and with two archival groups: a delayed
      progress feedback and CST feedback group (n = 1374) and a treatment-as-usual
      control group (n = 1445). Progress feedback to therapists improved outcomes,
      especially for cases at risk for a negative outcome, but direct progress feedback
      to clients did not. Effects were significantly enhanced by using the manual-based
      CST. There were no significant differences in outcome between the 1-week-delayed
      CST feedback and 2-week-delayed CST feedback groups; however, clients in the week
      delayed CST feedback timing condition attended three less sessions, on average,
      than their 2-week-delayed CST feedback counterparts while maintaining similar
      treatment gains. Results were interpreted as supporting the value of monitoring
      client progress and feeding back this information to therapists as well as
      assisting therapists in problem solving with cases at risk for treatment failure.

PMID- 19115450
TI  - The development of a 'best practice' service for women in a medium-secure
      psychiatric setting: treatment components and evaluation.
AB  - The inadequacy of inpatient facilities for women with severe psychiatric and co
      morbid difficulties has been repeatedly documented. The establishment of
      effective therapeutic programmes for women in medium psychiatric facilities is
      also in their infancy, and little research has been undertaken. This article
      describes the development of a 'best practice' psychological treatment programme
      for women with a dual diagnosis. Emphasis is placed on the need to develop
      further intensive gender-specific services using an established model for
      effective therapeutic service development. In addition to a detailed description
      of the group therapy programme, staff training initiatives, methods for ensuring
      treatment integrity and a methodology for service evaluation is given.

PMID- 19115451
TI  - Patients' perspective on homework assignments in cognitive-behavioural therapy.
AB  - Homework assignments are an indispensable part of cognitive-behavioural therapy.
      During the past two decades, a growing number of studies have shed light on its
      characteristics and effects. However, most studies primarily consider the
      therapists' view, and little is known about the use of supportive strategies to
      implement homework assignments in psychotherapy and about patients' attitudes
      towards regular assignments. To fill this gap, we assessed the attitudes towards
      homework assignments of 80 outpatients. In addition, those who had received a
      task during the past session (75%) were asked to report characteristics of their
      task as well as therapists' behaviour strategies during the assignment of the
      task. One week later, therapists rated the extent of completion of the task.
      Results showed that the patients generally had a positive attitude towards
      homework and that they accomplished most of the tasks. With regard to the
      therapists' behaviour during the assignment of the task, there seems to be room
      for improvement.

PMID- 19115452
TI  - Cognitive biases in depressed and non-depressed referred youth.
AB  - This study examined cognitive vulnerability in both depressed and non-depressed
      referred youngsters. Formerly depressed (FD) children and adolescents (n = 16)
      were compared to a currently depressed (CD) group (n = 18) on a self-referent
      encoding and memory task imbedded in a mood induction paradigm. In order to test
      the specificity of the findings to depression, the results of the FD were further
      compared with those of a clinical but never depressed (ND) group (n = 39)
      diagnosed with anxiety and/or disruptive behaviour disorders. The study confirmed
      the hypothesized differences between the groups in terms of self-referent
      encoding bias. Both the ND (p < 0.001) and FD (p < 0.001) group rated more
      positive words than negative words as self-descriptive while the CD endorsed a
      closer balance of positive and negative words (non-significant difference). No
      interaction effect was found for the recall task. The FD group evinced a similar
      memory bias than the CD group. However, also in the ND group, the number of
      proportional recalled positive words did not differ from the proportional
      recalled negative words. The findings yielded no evidence for a depression
      specific information-processing bias. However, all subjects (FD, CD as well as
      ND) exhibited a memory bias and therefore 'clinical status' is considered as a
      cognitive vulnerability risk factor for developing a depressive disorder in the
      future.

PMID- 19115453
TI  - Physiological reactivity to stress and parental support: comparison of clinical
      and non-clinical adolescents.
AB  - An Alarm Stress Task was developed to study affect regulation in the context of
      parent-child interactions in adolescents (mean age = 12.72, standard deviation =
      2.06) with (n = 20) and without (n = 20) mental health problems. Changes in heart
      rate (HR), preejection period (PEP) and respiratory sinus arrhythmia (RSA) were
      used as indicators of affect regulation. HR increased, and PEP and RSA decreased
      significantly in reaction to a suggested failure on a simple task, indicating
      that this procedure induced affective arousal in adolescents. During reunion with
      the parent, RSA increased significantly. Support seeking on reunion was
      associated with stronger parasympathetic reactivity during stress and reunion,
      consistent with the model that the parasympathetic system is involved when affect
      is regulated by social engagement. Quality of parent-adolescent interactive
      behaviour was overall lower in the clinical sample. Individual and relationship
      based processes of affect regulation may be simultaneously assessed, highlighting
      the continuing importance of the parent-child relationship in adolescence for
      affect regulation and mental health.

PMID- 19115454
TI  - Counterfactual thinking and functional differences in depression.
AB  - The purpose of the studies reported in this paper was to evaluate the function of
      counterfactual thinking (CT) in depression. In Experiment 1, depressed and non
      depressed participants were asked to imagine themselves as the protagonist of a
      hypothetical situation, and to think counterfactually about three different
      scenarios. The results showed that there was a similar CT style (in terms of
      direction, structure and focus of mutation) for the depressed and the non
      depressed groups. It was also found that the perceived preparation for a future
      similar situation increased after CT and, contrary to our hypotheses, this effect
      was observed in both groups. In Experiment 2, a real-life situation was used (a
      course examination) in which participants experienced a negative outcome (a poor
      score on the test). Again, it was observed that depressed and non-depressed
      participants showed the same CT style, but non-depressed participants were more
      likely to use CT spontaneously. In addition, the second study showed further
      differences between the two groups: depressed participants not only showed a lack
      of cognitive benefits from thinking counterfactually (i.e., after CT they do not
      feel more prepared for future similar events, nor able to avoid a similar bad
      outcome, in contrast to the non-depressed participants), but also show a lack of
      behavioural changes (both intentions to change and actual changes over the
      subsequent week). In conclusion, these results provide evidence about the
      function of CT both in depressed and in non-depressed thinking, and highlight
      both the similarities and differences for these two groups.

PMID- 19115455
TI  - Cognitive-behavioural treatment of first diagnosis bipolar disorder.
AB  - Cognitive-behavioural therapy can lead to significant improvements in relapse and
      inter-episode functioning for individuals with an established course of bipolar
      disorder. Both psychiatric and psychological models of bipolar disorder suggest
      that there may be additional benefits in offering this approach earlier in the
      illness course. This paper reports on the application of a modified cognitive
      behavioural approach for individuals after first diagnosis of bipolar disorder
      using a single case approach across seven participants. Evidence is reported for
      improvements in mood symptoms and hopelessness following treatment, as well as
      increased self-control behaviours, more stable activity patterns and increased
      ability to detect and coping with early warning signs. Implications of these
      initial findings for future research are discussed.

PMID- 19115456
TI  - Prevalence and prediction of re-experiencing and avoidance after elective
      surgical abortion: a prospective study.
AB  - OBJECTIVE: This study investigated short-term re-experiencing and avoidance after
      elective surgical abortion. In addition, it was prospectively investigated
      whether peritraumatic dissociation and pre-abortion dissociative tendencies and
      alexithymia predict re-experiencing and avoidance. METHOD: In a prospective
      observational design, Dutch-speaking women presenting for first trimester
      elective surgical abortion completed self-report measures for dissociative
      tendency and alexithymia. Peritraumatic dissociation was measured immediately
      post-abortion. Re-experiencing and avoidance were measured 2 months post
      abortion. RESULTS: Participants reported moderately elevated levels of re
      experiencing and avoidance that exceeded a clinical cut-off point for 19.4% of
      the participants. Peritraumatic dissociation predicted intrusion and avoidance at
      2 months. In addition, avoidance was predicted by the alexithymic aspect of
      difficulty describing feelings. CONCLUSIONS: Re-experiencing and avoidance after
      elective surgical abortion represent a significant clinical problem that is
      predicted by peritraumatic dissociation and alexithymia. Psychological screening
      and intervention might be a useful adjunct to elective abortion procedures.

PMID- 19115457
TI  - Are normal and complicated grief different constructs? a confirmatory factor
      analytic test.
AB  - Nowadays, much debate in the bereavement domain is directed towards the inclusion
      of Complicated Grief (CG) as a separate category in the Diagnostic and
      Statistical Manual of Mental Disorders. Important within this discussion is the
      conceptual relationship between CG reactions and normal grief (NG) reactions.
      This study aims at elucidating this relationship by using data from 456 bereaved
      young adults, aged 17 to 25 years. We examined the structural distinctiveness of
      CG and NG reactions, using two criteria sets. The first set ties in with previous
      research in bereaved adults on the distinctiveness of CG and NG and allows to
      test the replicability of earlier findings. The second set links up with the
      recently revised criteria for CG and permits to investigate whether earlier
      findings hold for the new criteria. For both sets, two models for NG and CG were
      compared using confirmatory factor analytic procedures. These analyses revealed
      that CG and NG reactions can be distinguished by their very nature, except for
      one CG reaction (viz. 'yearning'), that loaded on both factors.

PMID- 19115458
TI  - Predicting the effect of psychoeducational group treatment for hypochondriasis.
AB  - Both individual cognitive-behavioural therapy and short-term psychoeducational
      courses have shown to be effective in reducing hypochondriacal complaints.
      However, it is unknown which patients benefit from treatment. The aim of the
      present study is to explore which variables predict treatment outcome in a pooled
      group of 140 participants of a psychoeducational course. Predictor variables were
      a) pretreatment hypochondriasis, b) age, c) gender, d) level of education, e)
      duration of hypochondriacal complaints, f) severity of depressive complaints, g)
      severity of trait anxiety, and h) treatment expectation. The target scores were
      residual gain scores of hypochondriacal complaints. Results showed that more
      severe hypochondriacal complaints at pre- and post-test correlated significantly
      with more severe hypochondriacal complaints later. Furthermore, higher trait
      anxiety and older age predicted less treatment gain in hypochondriacal
      complaints. More research of which variables can predict treatment outcome is
      needed.

PMID- 19115459
TI  - Comparison of therapeutic action, style and content in cognitive-behavioural and
      psychodynamic group therapy under clinically representative conditions.
AB  - It is still an open question whether psychotherapists adhere to their therapeutic
      conceptions in routine practice (clinician's treatment adherence) and thus to
      what extent the two most common approaches, cognitive-behavioural (CBT) and
      psychodynamic therapy (PDT), differ from each other as theoretically expected
      (treatment differentiation). This holds true especially in case of group
      therapy.The study compares essential process components of CBT and PDT group
      treatments under clinically representative conditions using non-participating
      observer ratings. Results demonstrate that CBT group therapists use more
      cognitive, behavioural and psychoeducational strategies, foster self-efficacy to
      a larger extent and are more supporting and empathetic. PDT group therapists use
      more interpretative and confrontative interventions and focus on interactional
      and dynamic aspects. The results strongly support that not only in individual
      psychotherapy-as shown in prior research-but also in the group setting do CBT and
      PDT reveal very distinct profiles and that therapists primarily abide by their
      theoretical training also in clinical practice. They allow one to identify
      differential process components of the group setting and to trace back parameters
      of outcome to the process of CBT and PDT for clinical routines.

PMID- 19115460
TI  - The factorial structure of the Outcome Questionnaire-45: a study with an Italian
      sample.
AB  - In this article, the authors study the factorial structure of the Italian
      translation of the Outcome Questionnaire 45 (OQ-45) in a sample of college
      students (n = 522) and psychiatric outpatients (n = 301). The relative goodness
      of fit of six competing models of the OQ-45 was examined using confirmatory
      factor analysis (CFA). Specifically, the study examined the relative fit of the
      most frequently presented models in the literature and three alternative models.
      Results of the CFA provided support for the four factor bi-level solution,
      suggesting that the OQ-45 is a multidimensional instrument that contains one
      general factor and multiple unique subscale factors.

PMID- 19115461
TI  - Psychometric characteristics of the Penn State Worry Questionnaire and
      Metacognitions Questionnaire-30 and metacognitive predictors of worry and
      obsessive-compulsive symptoms in a Turkish sample.
AB  - The purpose of the present study was twofold. First, to examine the psychometric
      properties of the Penn State Worry Questionnaire (PSWQ) and the Metacognitions
      Questionnaire-30 (MCQ-30) in a Turkish sample. Second, to investigate
      metacognitive predictors of pathological worry and obsessive-compulsive (o-c)
      symptoms in this group. The sample included 561 non-clinical participants.
      Consistent with non-English versions, the Turkish version of the PSWQ was found
      to have a two-factor structure. The MCQ-30 was shown to be composed of five
      factors similar to the English version. Reliability analyses indicated that both
      the PSWQ and MCQ-30 possessed high internal consistency, split-half reliability
      and test-retest coefficients. As expected, both scales positively correlated with
      measures of o-c symptoms, trait anxiety, and anxiety and depression, as well as
      with each other. Negative and positive metacognitive beliefs about worry were
      significant predictors of both pathological worry and o-c symptoms. Cognitive
      confidence emerged as a specific predictor of worry, while beliefs about the need
      to control thoughts emerged as a unique predictor of o-c symptoms.

PMID- 19115462
TI  - A pilot study of cognitive behaviour therapy for panic disorder augmented by
      panic surfing.
AB  - This pilot study reports the outcome of cognitive behaviour therapy for panic
      disorder augmented by panic surfing. This treatment approach encourages
      acceptance of feelings rather than control of symptoms and anxiety, at the same
      time also targeting catastrophic misinterpretations, bodily vigilance and safety
      seeking behaviours. Eighteen participants completed a brief group treatment for
      panic disorder incorporating psychoeducation, panic surfing, interoceptive
      exposure, graded exposure and cognitive restructuring. Significant improvements
      occurred over the course of this treatment and were maintained at a 1-month
      follow-up. Results suggest that cognitive behaviour therapy augmented by panic
      surfing may be effective in the treatment of panic disorder, but there is a need
      for controlled studies and investigation of the relative contribution of its
      various components.

PMID- 19115463
TI  - Importance of gastrin in the pathogenesis and treatment of gastric tumors.
AB  - In addition to regulating acid secretion, the gastric antral hormone gastrin
      regulates several important cellular processes in the gastric epithelium
      including proliferation, apoptosis, migration, invasion, tissue remodelling and
      angiogenesis. Elevated serum concentrations of this hormone are caused by many
      conditions, particularly hypochlorhydria (as a result of autoimmune or
      Helicobacter pylori (H pylori)-induced chronic atrophic gastritis or acid
      suppressing drugs) and gastrin producing tumors (gastrinomas). There is now
      accumulating evidence that altered local and plasma concentrations of gastrin may
      play a role during the development of various gastric tumors. In the absence of H
      pylori infection, marked hypergastrinemia frequently results in the development
      of gastric enterochromaffin cell-like neuroendocrine tumors and surgery to remove
      the cause of hypergastrinemia may lead to tumor resolution in this condition. In
      animal models such as transgenic INS-GAS mice, hypergastrinemia has also been
      shown to act as a cofactor with Helicobacter infection during gastric
      adenocarcinoma development. However, it is currently unclear as to what extent
      gastrin also modulates human gastric adenocarcinoma development. Therapeutic
      approaches targeting hypergastrinemia, such as immunization with G17DT, have been
      evaluated for the treatment of gastric adenocarcinoma, with some promising
      results. Although the mild hypergastrinemia associated with proton pump inhibitor
      drug use has been shown to cause ECL-cell hyperplasia and to increase H pylori
      induced gastric atrophy, there is currently no convincing evidence that this
      class of agents contributes towards the development of gastric neuroendocrine
      tumors or gastric adenocarcinomas in human subjects.

PMID- 19115464
TI  - Eosinophilic esophagitis.
AB  - Eosinophilic esophagitis is increasingly recognized in adults. The diagnosis is
      based on the presence of both typical symptoms and pathologic findings on
      esophageal biopsy. Patients usually present with dysphagia, food impaction and/or
      reflux-like symptoms, and biopsy of the esophagus shows more than 15 eosinophils
      per high-power field. In addition, it is essential to exclude the presence of
      known causes of tissue eosinophilia such as gastroesophageal reflux disease,
      infections, malignancy, collagen vascular diseases, hypersensitivity, and
      inflammatory bowel disease. There are no standardized protocols for the therapy
      of eosinophilic esophagitis. A variety of therapeutic approaches including acid
      suppression, dietary modifications, topical corticosteroids and endoscopic
      dilation can be used alone or in combination.

PMID- 19115466
TI  - Pancreatic pseudocyst.
AB  - Pancreatic pseudocysts are complications of acute or chronic pancreatitis.
      Initial diagnosis is accomplished most often by cross-sectional imaging.
      Endoscopic ultrasound with fine needle aspiration has become the preferred test
      to help distinguish pseudocyst from other cystic lesions of the pancreas. Most
      pseudocysts resolve spontaneously with supportive care. The size of the
      pseudocyst and the length of time the cyst has been present are poor predictors
      for the potential of pseudocyst resolution or complications, but in general,
      larger cysts are more likely to be symptomatic or cause complications. The main
      two indications for some type of invasive drainage procedure are persistent
      patient symptoms or the presence of complications (infection, gastric outlet or
      biliary obstruction, bleeding). Three different strategies for pancreatic
      pseudocysts drainage are available: endoscopic (transpapillary or transmural)
      drainage, percutaneous catheter drainage, or open surgery. To date, no
      prospective controlled studies have compared directly these approaches. As a
      result, the management varies based on local expertise, but in general,
      endoscopic drainage is becoming the preferred approach because it is less
      invasive than surgery, avoids the need for external drain, and has a high long
      term success rate. A tailored therapeutic approach taking into consideration
      patient preferences and involving multidisciplinary team of therapeutic
      endoscopist, interventional radiologist and pancreatic surgeon should be
      considered in all cases.

PMID- 19115465
TI  - Gastroparesis: current diagnostic challenges and management considerations.
AB  - Gastroparesis refers to abnormal gastric motility characterized by delayed
      gastric emptying in the absence of mechanical obstruction. The most common
      etiologies include diabetes, post-surgical and idiopathic. The most common
      symptoms are nausea, vomiting and epigastric pain. Gastroparesis is estimated to
      affect 4% of the population and symptomatology may range from little effect on
      daily activity to severe disability and frequent hospitalizations. The gold
      standard of diagnosis is solid meal gastric scintigraphy. Treatment is multimodal
      and includes dietary modification, prokinetic and anti-emetic medications, and
      surgical interventions. New advances in drug therapy, and gastric electrical
      stimulation techniques have been introduced and might provide new hope to
      patients with refractory gastroparesis. In this comprehensive review, we discuss
      gastroparesis with emphasis on the latest developments; from the perspective of
      the practicing clinician.

PMID- 19115467
TI  - Cystic neoplasms of the pancreas: a diagnostic challenge.
AB  - Cystic neoplasms of the pancreas are increasingly recognized due to the expanding
      use and improved sensitivity of cross-sectional abdominal imaging. Major advances
      in the last decade have led to an improved understanding of the various types of
      cystic lesions and their biologic behavior. Despite significant improvements in
      imaging technology and the advent of endoscopic-ultrasound (EUS)-guided fine
      needle aspiration, the diagnosis and management of pancreatic cystic lesions
      remains a significant clinical challenge. The first diagnostic step is to
      differentiate between pancreatic pseudocyst and cystic neoplasm. If a pseudocyst
      has been effectively excluded, the cornerstone issue is then to determine the
      malignant potential of the pancreatic cystic neoplasm. In the majority of cases,
      the correct diagnosis and successful management is based not on a single test but
      on incorporating data from various sources including patient history, radiologic
      studies, endoscopic evaluation, and cyst fluid analysis. This review will focus
      on describing the various types of cystic neoplasms of the pancreas, their
      malignant potential, and will provide the clinician with a comprehensive
      diagnostic approach.

PMID- 19115468
TI  - ERCP wire systems: the long and the short of it.
AB  - Guidewires are routinely used at the time of endoscopic retrograde
      cholangiopancreatography (ERCP) to gain and maintain access to the desired duct
      and aid in the advancement of various devices. Limitations of the traditional
      long-wire systems have led to the introduction of three proprietary short-wire
      systems. These systems differ in many respects but share two main principles:
      They lock a shorter wire in position to allow advancement or removal of various
      devices without displacement of the wire and they all allow for physician control
      of the wire. In this comprehensive review, we describe the key features of the
      three currently available short-wire systems: RX, Fusion and V systems. We also
      focus on the potential benefits and drawbacks that accompany the short-wire
      concept as a whole and each specific system in particular. Although the available
      data are limited, it appears that the use of the short-wire systems lead to
      reduced procedure, fluoroscopy and device exchange times, decreased sedation
      requirements, improved wire stability and increased endoscopist control of the
      wire. Furthermore, the physician-controlled wire-guided cannulation has the
      potential to decrease ampullary trauma and the rate of post-ERCP pancreatitis.
      The short guidewire systems appear to be an improvement over the traditional long
      wire systems but further studies directly comparing the two approaches are
      needed.

PMID- 19115469
TI  - Colorectal cancer surveillance in inflammatory bowel disease: the search
      continues.
AB  - Patients with inflammatory bowel disease (IBD) are at increased risk for
      colorectal cancer (CRC). Risk factors for the development of CRC in the setting
      of IBD include disease duration, anatomic extent of disease, age at time of
      diagnosis, severity of inflammation, family history of colon cancer, and
      concomitant primary sclerosing cholangitis. The current surveillance strategy of
      surveillance colonoscopy with multiple random biopsies most likely reduces
      morbidity and mortality associated with IBD-related CRC. Unfortunately,
      surveillance colonoscopy also has severe limitations including high cost,
      sampling error at time of biopsy, and interobserver disagreement in
      histologically grading dysplasia. Furthermore, once dysplasia is detected there
      is disagreement about its management. Advances in endoscopic imaging techniques
      are already underway, and may potentially aid in dysplasia detection and improve
      overall surveillance outcomes. Management of dysplasia depends predominantly on
      the degree and focality of dysplasia, with the mainstay of management involving
      either proctocolectomy or continued colonoscopic surveillance. Lastly, continued
      research into additional chemopreventive agents may increase our arsenal in
      attempting to reduce the incidence of IBD-associated CRC.

PMID- 19115471
TI  - Recent advances and remaining gaps in our knowledge of associations between gut
      microbiota and human health.
AB  - The complex gut microbial flora harbored by individuals (microbiota) has long
      been proposed to contribute to intestinal health as well as disease. Pre- and
      probiotic products aimed at improving health by modifying microbiota composition
      have already become widely available and acceptance of these products appears to
      be on the rise. However, although required for the development of effective
      microbiota based interventions, our basic understanding of microbiota variation
      on a population level and its dynamics within individuals is still rudimentary.
      Powerful new parallel sequence technologies combined with other efficient
      molecular microbiota analysis methods now allow for comprehensive analysis of
      microbiota composition in large human populations. Recent findings in the field
      strongly suggest that microbiota contributes to the development of obesity,
      atopic diseases, inflammatory bowel diseases and intestinal cancers. Through the
      ongoing National Institutes of Health Roadmap 'Human Microbiome Project' and
      similar projects in other parts of the world, a large coordinated effort is
      currently underway to study how microbiota can impact human health. Translating
      findings from these studies into effective interventions that can improve health,
      possibly personalized based on an individuals existing microbiota, will be the
      task for the next decade(s).

PMID- 19115470
TI  - Evaluation and management of patients with refractory ascites.
AB  - Some patients with ascites due to liver cirrhosis become no longer responsive to
      diuretics. Once other causes of ascites such as portal vein thrombosis,
      malignancy or infection and non-compliance with medications and low sodium diet
      have been excluded, the diagnosis of refractory ascites can be made based on
      strict criteria. Patients with refractory ascites have very poor prognosis and
      therefore referral for consideration for liver transplantation should be
      initiated. Search for reversible components of the underlying liver pathology
      should be undertaken and targeted therapy, when available, should be considered.
      Currently, serial large volume paracentesis (LVP) and transjugular intrahepatic
      portasystemic stent-shunt (TIPS) are the two mainstay treatment options for
      refractory ascites. Other treatment options are available but not widely used
      either because they carry high morbidity and mortality (most surgical options)
      rates, or are new interventions that have shown promise but still need further
      evaluation. In this comprehensive review, we describe the evaluation and
      management of patients with refractory ascites from the prospective of the
      practicing physician.

PMID- 19115472
TI  - Prevalence of clonorchiasis in patients with gastrointestinal disease: a Korean
      nationwide multicenter survey.
AB  - AIM: To investigate prevalence of Clonorchis sinensis in patients with
      gastrointestinal symptoms, and the relation of the infection to hepatobiliary
      diseases in 26 hospitals in Korea. METHODS: Consecutive patients who had been
      admitted to the Division of Gastroenterology with gastrointestinal symptoms were
      enrolled from March to April 2005. Of those who had been diagnosed with
      clonorchiasis, epidemiology and correlation between infection and hepatobiliary
      diseases were surveyed by questionnaire. RESULTS: Of 3080 patients with
      gastrointestinal diseases, 396 (12.9%) had clonorchiasis and 1140 patients
      (37.2%) had a history of eating raw freshwater fish. Of those with a history of
      raw freshwater fish ingestion, 238 (20.9%) patients had clonorchiasis.
      Cholangiocarcinoma was more prevalent in C. sinensis-infected patients than non
      infected patients [34/396 (8.6%) vs 145/2684 (5.4%), P = 0.015].
      Cholangiocarcinoma and clonorchiasis showed statistically significant positive
      cross-relation (P = 0.008). Choledocholithiasis, cholecystolithiasis,
      cholangitis, hepatocellular carcinoma, and biliary pancreatitis did not correlate
      with clonorchiasis. CONCLUSION: Infection rate of clonorchiasis was still high in
      patients with gastrointestinal diseases in Korea, and has not decreased very much
      during the last two decades. Cholangiocarcinoma was related to clonorchiasis,
      which suggested an etiological role for the parasite.

PMID- 19115473
TI  - Treatment of chronic proliferative cholangitis with c-myc shRNA.
AB  - AIM: To investigate the feasibility and effectiveness of c-myc shRNA in
      inhibiting the hyperplastic behavior and lithogenic potentiality of chronic
      proliferative cholangitis (CPC), in order to prevent stone recurrence and biliary
      restenosis. METHODS: An animal model of CPC was established by giving
      intralumenally 0.5 mL of c-myc shRNA. Then, the effects of c-myc shRNA on
      hyperplastic behavior and lithogenic potentiality of CPC were evaluated by
      histological observation, immunohistochemistry, real-time PCR and Western
      blotting for c-myc, proliferating cell nuclear antigen (PCNA), procollagen III,
      mucin 5AC, enzymatic histochemistry for beta-glucuronidase, and biochemistry for
      hydroxyproline in the diseased bile duct. RESULTS: Treatment with c-myc shRNA
      efficiently suppressed the hyperplasia of biliary epithelium, submucosal gland,
      and collagen fiber by inhibiting mRNA and protein expression of c-myc. More
      importantly, it decreased the lithogenic potentiality of CPC by inhibiting the
      expression of mucin 5AC and the secretion of endogenous beta-glucuronidase.
      Further investigation indicated that c-myc shRNA-3 had a better inhibitory effect
      on CPC. CONCLUSION: Treatment with c-myc shRNA-3 can control CPC and reduce the
      lithogenic potentiality of CPC.

PMID- 19115474
TI  - Seroepidemiology of hepatitis A virus in Kuwait.
AB  - AIM: To find the current seroepidemiology of hepatitis A virus (HAV) in Kuwait.
      METHODS: A total of 2851 Kuwaitis applying for new jobs were screened. RESULTS:
      HAV-positive cases were 28.8%; 59% were males and 41% were females. The highest
      prevalence was in the Ahmadi area. High prevalence was among the group of non
      educated rather than educated parents. This is the first study in Kuwait
      demonstrating the shifting epidemiology of HAV. CONCLUSION: This study reflects
      the need of the Kuwaiti population for an HAV vaccine.

PMID- 19115475
TI  - Iron homeostasis and H63D mutations in alcoholics with and without liver disease.
AB  - AIM: To evaluate the prevalence of HFE gene mutation and indices of disturbed
      iron homeostasis in alcoholics with and without liver disease. METHODS: One
      hundred and fifty-three heavy drinkers (defined as alcohol consumption > 80 g/d
      for at least 5 years) were included in the study. These comprised 78 patients
      with liver disease [liver disease alcoholics (LDA)] in whom the presence of liver
      disease was confirmed by liver biopsy or clinical evidence of hepatic
      decompensation, and 75 subjects with no evidence of liver disease, determined by
      normal liver tests on two occasions [non-liver disease alcoholics (NLDA)], were
      consecutively enrolled. Serum markers of iron status and HFE C282Y and H63D
      mutations were determined. HFE genotyping was compared with data obtained in
      healthy blood donors from the same geographical area. RESULTS: Gender ratio was
      similar in both study groups. LDA patients were older than NLDA patients (52 +/-
      10 years vs 48 +/- 11 years, P = 0.03). One third and one fifth of the study
      population had serum transferrin saturation (TS) greater than 45% and 60%
      respectively. Serum iron levels were similar in both groups. However, LDA
      patients had higher TS (51 +/- 27 vs 36 +/- 13, P < 0.001) and ferritin levels
      (559 +/- 607 ng/mL vs 159 +/- 122 ng/mL, P < 0.001), and lower total iron binding
      capacity (TIBC) (241 +/- 88 microg/dL vs 279 +/- 40 microg/dL, P = 0.001). The
      odds ratio for having liver disease with TS greater than 45% was 2.20 (95%
      confidence interval (CI): 1.37-3.54). There was no difference in C282Y allelic
      frequency between the two groups. However, H63D was more frequent in LDA patients
      (0.25 vs 0.16, P = 0.03). LDA patients had a greater probability of carrying at
      least one HFE mutation than NLDA patients (49.5% vs 31.6%, P = 0.02). The odds
      ratio for LDA in patients with H63D mutation was 1.57 (95% CI: 1.02-2.40).
      CONCLUSION: The present study confirms the presence of iron overload in
      alcoholics, which was more severe in the subset of subjects with liver disease,
      in parallel with an increased frequency of H63D HFE mutation.

PMID- 19115476
TI  - Use of albendazole sulfoxide, albendazole sulfone, and combined solutions as
      scolicidal agents on hydatid cysts (in vitro study).
AB  - AIM: To establish which scolicidal agents are superior and more suitable for
      regular use. METHODS: Echinococcus granulosus protoscoleces were obtained from 25
      patients with liver hydatid cysts. Various concentrations of albendazole sulfone,
      albendazole sulfoxide, and albendazole sulfone and albendazole sulfoxide mixed
      together in concentrations of 50 microg/mL, and H(2)O(2) in a concentration of
      4%, NaCl 20%, and 1.5% cetrimide-0.15% chlorhexidine (10% Savlon-Turkey) were
      used to determine the scolicidal effects. Albendazole (ABZ) derivatives and other
      scolicidal agents were applied to a minimum of 100 scoleces for 5 and 10 min. The
      degree of viability was calculated according to the number of living scolices per
      field from a total of 100 scolices observed under the microscope. RESULTS: After
      5 min, ABZ sulfone was 97.3% effective, ABZ sulfoxide was 98.4% effective, and
      the combined solution was 98.6% effective. When sulfone, sulfoxide and the
      combined solutions were compared, the combined solution seemed more effective
      than sulfone. However, there was no difference when the combined solution was
      compared with sulfoxide. After 10 min, hypertonic salt water, sulfone, sulfoxide,
      and the combined solution compared to other solutions looked more effective and
      this was statistically significant on an advanced level. When sulfone, sulfoxide,
      and the combined solutions were compared with each other, the combined solution
      appeared more effective than sulfone. When the combined solution was compared
      with sulfoxide, there was no difference. CONCLUSION: Despite being active, ABZ
      metabolites did not provide a marked advantage over 20% hypertonic saline.
      According to these results, we think creating a newly improved and more active
      preparation is necessary for hydatid cyst treatment.

PMID- 19115477
TI  - An unusual presentation of sclerosing mesenteritis as pneumoperitoneum: case
      report with a review of the literature.
AB  - Sclerosing mesenteritis is a rare condition that involves the small or large
      bowel mesentery. An unusual presentation of this condition, which led to
      difficult preoperative assessment and diagnosis, is described. This report is
      followed by a comprehensive review of the literature.

PMID- 19115478
TI  - Bile duct ligation in rats: a reliable model of hepatorenal syndrome?
AB  - The two most widely used experimental models of advanced liver disease are the
      administration of carbon tetrachloride, and common bile duct ligation (BDL),
      however, neither has been systematically evaluated as a model of hepatorenal
      syndrome (HRS). The BDL model in rats, studied at diverse time points, induced a
      progressive renal dysfunction without structural changes in the kidney. The
      authors concluded that BDL is a good model for further studies of HRS and its
      treatment. However, the renal impairment observed at the acute phase of the BDL
      model is based on a different pathophysiology than that of HRS. Specifically, in
      acute obstructive jaundice, cholemia predominates over parenchymal liver disease
      (reversible at this stage without portal hypertension or cirrhosis) and
      independently induces negative inotropic and chronotropic effects on the heart,
      impaired sympathetic vasoconstriction response and profound natriuresis and
      diuresis that might lead to volume depletion. In addition, systemic endotoxemia
      contributes to the prerenal etiology of renal impairment and promotes direct
      nephrotoxicity and acute tubular necrosis. On the other hand, the renal failure
      observed in the chronic BDL model (with development of biliary cirrhosis, portal
      hypertension and ascites) shares pathophysiological similarities with HRS, but
      the accordance of the chronic BDL model to the diagnostic criteria of HRS (e.g.
      absence of spontaneous bacterial peritonitis, no renal function improvement after
      plasma volume expansion) should have been confirmed. In conclusion, we think that
      the BDL model is not suitable for the study of the natural history of HRS, but
      the chronic BDL model might be valid for the study of established HRS and its
      potential therapies.

PMID- 19115479
TI  - Proceedings of the first global meeting on hepatitis A virus infection, 2007,
      Miami, Florida, USA.

PMID- 19115480
TI  - Autophagy research: lessons from metabolism.
AB  - Autophagy research continues to expand exponentially. Clearly autophagy and
      metabolism are intimately connected; however, the rapid expansion of research
      into this topic inevitably brings the risk that important basic knowledge of
      metabolism will be overlooked when considering experimental data. Unfortunately,
      unawareness of possible metabolic complications may sometimes lead to
      misinterpretation of the data obtained.

PMID- 19115481
TI  - The autophagic pathway is a key component in the lysosomal dependent entry of
      Trypanosoma cruzi into the host cell.
AB  - The etiologic agent of Chagas disease, Trypanosoma cruzi, infects mammalian cells
      activating a signal transduction cascade that leads to the formation of its
      parasitophorous vacuole. Previous works have demonstrated the crucial role of
      lysosomes in the establishment of T. cruzi infection. In this work we have
      studied the possible relationship between this parasite and the host cell
      autophagy. We show, for the first time, that the vacuole containing T. cruzi
      (TcPV) is decorated by the host cell autophagic protein LC3. Furthermore, live
      cell imaging experiments indicate that autolysosomes are recruited to parasite
      entry sites. Interestingly, starvation or pharmacological induction of autophagy
      before infection significantly increased the number of infected cells whereas
      inhibitors of this pathway reduced the invasion. In addition, the absence of Atg5
      or the reduced expression of Beclin 1 -- two proteins required at the initial
      steps of autophagosome formation -- limited parasite entry and reduced the
      association between TcPV and the classical lysosomal marker Lamp-1. These results
      indicate that mammalian autophagy is a key process that favors the colonization
      of T. cruzi in the host cell.

PMID- 19115482
TI  - Coenzyme Q deficiency triggers mitochondria degradation by mitophagy.
AB  - Coenzyme Q10 (CoQ) is a small lipophilic molecule critical for the transport of
      electrons from complexes I and II to complex III in the mitochondrial respiratory
      chain. CoQ deficiency is a rare human genetic condition that has been associated
      with a variety of clinical phenotypes. With the aim of elucidating how CoQ
      deficiency affects an organism, we have investigated the pathophysiologic
      processes present within fibroblasts derived from 4 patients with CoQ deficiency.
      Assays of cultured fibroblasts revealed decreased activities of complex II+III,
      complex III, and complex IV, reduced expression of mitochondrial proteins
      involved in oxidative phosphorylation, decreased mitochondrial membrane
      potential, increased production of reactive oxygen species (ROS), activation of
      mitochondrial permeability transition (MPT), and reduced growth rates. These
      abnormalities were partially restored by CoQ supplementation. Moreover, we
      demonstrate that CoQ deficient fibroblasts exhibited increased levels of
      lysosomal markers (beta-galactosidase, cathepsin, LC3, and Lyso Tracker), and
      enhanced expression of autophagic genes at both transcriptional and translational
      levels, indicating the presence of autophagy. Electron microscopy studies
      confirmed a massive degradation of the altered mitochondria by mitophagy.
      Autophagy in CoQ deficient fibroblasts was abolished by antioxidants or
      cyclosporin treatments suggesting that both ROS and MPT participate in this
      process. Furthermore, prevention of autophagy in CoQ deficient fibroblasts by 3
      methyl adenine or wortmannin, as well as the induction of CoQ deficiency in cells
      lacking autophagy (by means of genetic knockout of the Atg5 gene in mouse
      embryonic fibroblasts) resulted in apoptotic cell death, suggesting a protective
      role of autophagy in CoQ deficiency.

PMID- 19115483
TI  - Autophagy-assisted glycogen catabolism regulates asexual differentiation in
      Magnaporthe oryzae.
AB  - Autophagy, a conserved pathway for bulk cellular degradation and recycling in
      eukaryotes, regulates proper turnover of organelles, membranes and certain
      proteins. Such regulated degradation is important for cell growth and development
      particularly during environmental stress conditions, which act as key inducers of
      autophagy. We found that autophagy and MoATG8 were significantly induced during
      asexual development in Magnaporthe oryzae. An RFP-tagged MoAtg8 showed specific
      localization and enrichment in aerial hyphae, conidiophores and conidia. We
      confirmed that loss of MoATG8 results in dramatically reduced ability to form
      conidia, the asexual spores that propagate rice-blast disease. Exogenous supply
      of glucose or sucrose significantly suppressed the conidiation defects in a
      MoATG8-deletion mutant. Comparative proteomics based identification and
      characterization of Gph1, a glycogen phosphorylase that catalyzes glycogen
      breakdown, indicated that autophagy-assisted glycogen homeostasis is likely
      important for proper aerial growth and conidiation in Magnaporthe. Loss of Gph1,
      or addition of G6P significantly restored conidiation in the Moatg8Delta mutant.
      Overproduction of Gph1 led to reduced conidiation in wild-type Magnaporthe
      strain. We propose that glycogen autophagy actively responds to and regulates
      carbon utilization required for cell growth and differentiation during asexual
      development in Magnaporthe.

PMID- 19115484
TI  - Interplay between autophagy and apoptosis in TrkA-induced cell death.
AB  - Autophagy is a self-eating process to eradicate damaged proteins or organelles in
      cells. This process begins with formation of a double-membrane structure, called
      an autophagosome, which can sequester soluble proteins and organelles eventually
      degraded by lysosomal proteases after fusion with the lysosome. Autophagy was
      initially identified as a cell survival mechanism under stress conditions such as
      nutrient deprivation. More recently, it is also considered as type-II programmed
      cell death. In our recent report, we observed that overexpression of TrkA caused
      massive cell death via both apoptosis and autophagy. Overexpression of TrkA
      abated catalase activity and subsequently resulted in the production of a large
      amount of reactive oxygen species in cells. These consequences led to autophagic
      cell death. The autophagic cell death in TrkA-overexpressing cells was validated
      by GFP-LC3 dot formation, production of autophagosomes or acidic vacuoles, LC3
      lipidation, and depletion of autopahgy-related genes. In addition, we also
      observed some evidence for apoptosis in TrkA-expressing cells. Many cells
      expressing TrkA exhibited annexin V-positive staining, activation of caspase-7
      and BAX. Moreover, TrkA activated the JNK pathway, leading to phosphorylation of
      H2AX. In this report, we suggest that two cell death mechanisms occur
      simultaneously and interlink with each other. The JNK-calpain pathway might be a
      central process to mediate the two processes in TrkA-overexpressing cells,
      although further study still remains to prove the interplay between autophagy and
      apoptosis.

PMID- 19115485
TI  - Composite lymphoma: EBV-positive classic Hodgkin lymphoma and peripheral T-cell
      lymphoma: a case report.
AB  - Composite lymphomas are rare and defined as hematopoietic neoplasms with more
      than 1 malignant lymphomatous clone showing different phenotypic features. Of all
      possible combinations between non-Hodgkin lymphomas, B cell or T cell, and
      Hodgkin lymphoma, the least frequent are the ones combining T-cell non-Hodgkin
      lymphoma and classic Hodgkin lymphoma. We report a case of a 55-year-old woman
      with cervical and mediastinal lymphadenopathy, fever, weight loss, and night
      sweats. A cervical lymph node biopsy revealed a composite lymphoma with classic
      Hodgkin lymphoma and peripheral T-cell lymphoma components. The bone marrow was
      not involved. The patient refused treatment and died of disease progression 2
      months after diagnosis. The biopsied lymph node showed 2 distinct populations,
      one composed of large cells including typical Reed-Sternberg cells and their
      variants, with expression of CD30, CD15, PAX5, and LMP-1. The other component was
      more abundant and comprised polymorphic medium-sized cells with convoluted
      nuclei; CD3, CD5, CD2, and CD4 expression; and negativity for CD30, cytotoxic
      granules, and B-cell markers. Epstein-Barr virus DNA of subtype A was identified
      only in the Hodgkin cells. Clonal T-cell receptor gamma and beta gene
      rearrangements were detected in the T-cell component, whereas monoclonal
      immunoglobulin H gene rearrangement was found in the Hodgkin cells.

PMID- 19115486
TI  - Primary cerebral diffuse large B-cell lymphoma relapsed solely in the skin with
      the same clonal origin.
AB  - Diffuse large B-cell lymphoma is the most common type of primary central nervous
      system (CNS) lymphoma(PCNSL) with poor prognosis. Relapse occurs early and most
      commonly in CNS, whereas systemic relapse solely in skin is exceptional. We
      presented a unique case of PCNSL in an 82-year-old man with 2 consecutive skin
      relapses without concomitant local failure or other systemic involvement. The
      lymphoma cells of all 3 specimens were of the same histology and immunophenotype
      with expression of CD20, IgM, bcl-2, bcl-6, and MUM1 but not CD3, CD10, CD30,
      IgD, cyclin D1,or cutaneous lymphocyte-associated antigen. The skin tumors were
      in the dermis and subcutis with a spared grenz zone. The brain and skin tumors
      demonstrated the same clonal origin by B-cell clonality study followed by cloning
      and sequencing. To our knowledge, this is the first case of PCNSL relapsed solely
      in the skin with proven clonal identity.

PMID- 19115487
TI  - Ectopic (mediastinal) parathyroid adenoma with prominent lymphocytic
      infiltration.
AB  - Parathyroid adenoma with prominent lymphocytic infiltrates is very rare, with
      only 8 previously reported cases in the English scientific literature. Cases with
      prominent lymphocytic infiltrates of ectopic (mediastinal) parathyroid adenomas
      have not been reported. The prominent lymphocytic infiltration may make the
      diagnosis difficult on frozen sections, even on permanent histologic sections. We
      herein describe a case of ectopic (mediastinal) parathyroid adenoma with
      prominent lymphocytic infiltration in a 29-year-old man with hyperparathyroidism
      for 4 years. Immunohistochemical studies were important in making such a
      diagnosis.

PMID- 19115488
TI  - About the z-multiplier in total error calculations.
AB  - BACKGROUND: Total error (TE) in analytical measurement is calculated as
      systematic error (SE) plus z-times random error (RE). The z-multiplier is
      typically chosen at the 95% probability level, being 1.96 in the absence of SE is
      of considerable magnitude (one-sided 95% probability). Up to now, no SE/RE ratio
      dependent z-values have been considered. Here, we present z-values for SE/RE
      ratios ranging from 0 to 1. METHODS: The z-multiplier (95% probability level) was
      empirically obtained by modulation of the standard normal distribution with the
      EXCEL NORMDIST function (Microsoft EXCEL 2002). In total, five distributions
      representing SE/RE ratios between 0 and 1 were calculated, so that the total
      probability outside a TE boundary +/- 1.96 sigma was in the order of 5.013%.
      RESULTS: For distributions with SE/RE ratios ranging from 0 to 1 that satisfy the
      aforementioned total probability outside a TE boundary +/- 1.96 sigma, we found
      that the associated z-multipliers exhibit values from 1.96 (SE/RE = 0), 1.769
      (SE/RE = 0.25), 1.68 (SE/RE = 0.5), 1.651 (SE/RE = 0.75) TO 1.645 (SE/RE = 1).
      The respective probability values beyond +/- 1.96 sigma were 2.5%/2.5%,
      1.165%/3.849%, 0.368%/4.645%, 0.081%/4.934%, and 0.013%/5% for the SE/RE ratios
      of 0, 0.25, 0.5, 0.75, and 1. CONCLUSIONS: The results show that at SE/RE ratios
      > 0.75 the one-sided 95% probability level is practically reached. The results
      allow a refined calculation of TE at specified SE/RE ratios and a general
      understanding of the relevance of two- and one-sided probabilities at different
      SE/RE ratios.

PMID- 19115489
TI  - Study of proliferating trichilemmal tumor with PCR for HPV.

PMID- 19115490
TI  - Thrombolysis 3 to 4.5 hours after acute ischemic stroke.

PMID- 19115491
TI  - Thrombolysis 3 to 4.5 hours after acute ischemic stroke.

PMID- 19115492
TI  - Thrombolysis 3 to 4.5 hours after acute ischemic stroke.

PMID- 19115493
TI  - Accuracy of CT colonography for colorectal cancer screening.

PMID- 19115495
TI  - [Nutrition researchers and food industry].

PMID- 19115494
TI  - Accuracy of CT colonography for colorectal cancer screening.

PMID- 19115496
TI  - [The knowledge of science is only a part of the "truth"].

PMID- 19115497
TI  - What's in a name? Terminology in emergency care in South Africa.

PMID- 19115498
TI  - Staying independent in our later years.  There are many ways to keep on the move
      and living on your own in older age.

PMID- 19115499
TI  - Head maneuvers work best for common vertigo.

PMID- 19115500
TI  - Experts call for home blood pressure monitoring.

PMID- 19115501
TI  - FDA approves one drug for irritable bowel syndrome but suspends another.

PMID- 19115502
TI  - By the way, doctor.  I've seen a lot of Internet ads for Hoodia, a natural
      supplement that suppresses your appetite.  What do you know about it?  Does it
      work, is it safe?

PMID- 19115503
TI  - National and international registries of rare bleeding disorders.
AB  - Rare bleeding disorders (RBDs) are autosomal recessive disorders, representing 3
      5% of all the inherited deficiencies of coagulation factors. Their frequency in
      the general population ranges from 1:500,000 to 1:2 millions. In countries with a
      high rate of consanguineous marriages RBDs occur more frequently, representing a
      significant clinical and social problem. Patients affected by RBDs have a wide
      spectrum of clinical symptoms that vary from a mild or moderate bleeding tendency
      to potentially serious or life-threatening haemorrhages. Current treatment is
      based on both replacement therapy and non-transfusional treatment. However,
      despite the existence of several concentrates, there is no Factor V concentrate
      available for the treatment of Factor V deficiency, yet. In 2004, to improve the
      understanding of RBDs prevalence, diagnosis and treatments, the Rare Bleeding
      Disorders database (RBDD, www.rbdd.org) was developed. The RBDD project allowed
      the collection of epidemiological information on 3,230 patients from 66 Centres
      scattered all over the world. Epidemiological data can also be derived from the
      annual survey of the World Federation of Hemophilia (www.wfh.org) and from other
      existing national registries. However, these data are not homogenous and global
      surveys provide a non-real picture of the distribution of RBDs, as about 50% of
      data refers to European patients. Hence, we focused on Europe and, thanks to a
      European project (EN-RBD), we set up a network of 10 Treatment Centres to develop
      a homogeneous communication tool for inserting, managing and viewing information
      on RBD patients (www.rbdd.eu). This on-line database resulted to be a powerful
      tool to improve the quality of data collection. Preliminary results showed that a
      homogeneous and harmonized data collection using a unique model will help to have
      more accurate data for statistical analysis.

PMID- 19115504
TI  - [Gingival fibromatosis (hereditary hyperplastic gingivitis) in a wild European
      red fox (Vulpes vulpes)].
AB  - This report describes a case of gingival fibromatosis in an otherwise healthy and
      well nourished wild European red fox (Vulpes vulpes), which was shot by a hunter
      and submitted to the state laboratory in the context of the rabies monitoring
      program of the federal state of Brandenburg, Germany. At necropsy, a severe
      papillomatous proliferation of the complete gingival tissue of the upper and
      lower jaw was present. This gingival proliferation had already resulted in
      malocclusion, loosening and loss of several incisival, premolar and molar teeth.
      Histologically, the primary lesion was a massive increase in the amount of
      collagen rich and relatively avascular connective tissue within the gingival
      lamina propria mucosae. A papillomavirus infection was excluded by electron
      microscopy, immunohistochemistry and molecular biological methods. The gingival
      lesions in the red fox are identical to those seen in hereditary hyperplastic
      gingivitis in farmed silver foxes and hereditary gingival fibromatosis in man. It
      is presumed that, in analogy to the genetic diseases in silver foxes and man, a
      still unidentified genetic defect is responsible for the development of the
      disease in the red fox, too.

PMID- 19115505
TI  - The surgical treatment of mitral stenosis: the first heart operation.
AB  - Although several surgical procedures had been introduced for the relief or
      correction of various congenital and acquired heart diseases during the early
      decades of the 20th century, the first performed inside the heart was that for
      mitral stenosis. For this reason, it has particular significance. Although some
      surgical advances can be characterized as dramatic and may be quickly adopted in
      medical practice, the history of this approach to mitral stenosis was notable for
      prolonged resistance from existing medical authorities. There were also frequent
      technical setbacks in implementing surgical treatment of this common and often
      fatal disease.In conclusion, as physicians and surgeons of the present and future
      seek novel ways to alleviate or cure the current overwhelming problems
      confronting them (e.g., refractory end-stage heart failure, Alzheimer's disease),
      the story of mitral stenosis might well serve as a lesson of how long and arduous
      such efforts might turn out to be.

PMID- 19115506
TI  - Globalization and health: Venezuela and Cuba.

PMID- 19115507
TI  - [Mental diseases and drug provision of patients in Kazakhstan Republic].

PMID- 19115509
TI  - [Attention deficit hyperactivity disorder: clinical heterogeneity and
      possibilities of therapy].

PMID- 19115508
TI  - [Pandora's box: a microscope by Antoni van Leeuwenhoek].

PMID- 19115510
TI  - [Antipsychotic-induced weight gain: the possibilities of pharmacological
      correction].

PMID- 19115511
TI  - Radiotherapy errors spark investigations and reform.

PMID- 19115513
TI  - Erlotinib for the treatment of non-small-cell lung cancer.

PMID- 19115512
TI  - A review of human carcinogens--Part A: pharmaceuticals.

PMID- 19115514
TI  - 14th CTOS annual meeting.

PMID- 19115515
TI  - 94th RSNA Annual Meeting.

PMID- 19115516
TI  - 50th ASH Annual Meeting.

PMID- 19115517
TI  - San Antonio Breast Cancer Symposium.

PMID- 19115518
TI  - Ball: One man. One ball. One hour.

PMID- 19115519
TI  - Endocrinology of female puberty.
AB  - PURPOSE OF REVIEW: Puberty is the developmental process that culminates in
      reproductive capability. It is initiated by the release of gonadotropin-releasing
      hormone from specialized neurons of the hypothalamus to stimulate hormonal
      cascades and gonadal activation. The age of pubertal onset in girls may be
      younger than in previous decades, emphasizing the gaps in knowledge about
      pubertal onset and factors that modulate it. This review describes the state of
      the debate on the age of pubertal initiation, recent insights into the physiology
      of female puberty and its relationship to childhood obesity, and the regulation
      of gonadotropin-releasing hormone neurons at puberty. RECENT FINDINGS: Recent
      studies suggest that the average age of pubertal onset is decreasing in American
      girls, sparking controversy in defining the age at which puberty is considered
      precocious. Obese girls have hyperinsulinemia and hyperandrogenemia
      prepubertally, but it is unclear whether these factors play a role in the early
      onset of puberty in obese girls. The kisspeptin/G protein-coupled receptor 54
      pathway is important for pubertal initiation; an activating mutation in the
      pathway has been associated with precocious puberty. SUMMARY: The recent trend
      toward obesity has been proposed to play a role in the cause of early puberty in
      girls. The molecular mechanisms that initiate puberty are slowly being
      elucidated, with the discovery of kisspeptin prompting a novel direction in
      reproductive research.

PMID- 19115520
TI  - Effect of puberty on body composition.
AB  - PURPOSE OF REVIEW: Here we examine the effect of puberty on components of human
      body composition, including adiposity (total body fat, percentage body fat and
      fat distribution), lean body mass and bone mineral content and density. New
      methods and longitudinal studies have expended our knowledge of these remarkable
      changes. RECENT FINDINGS: Human differences in adiposity, fat free mass and bone
      mass reflect differences in endocrine status (particularly with respect to
      estrogens, androgens, growth hormone and IGF-1), genetic factors, ethnicity and
      the environment. During puberty, males gain greater amounts of fat free mass and
      skeletal mass, whereas females acquire significantly more fat mass. Both genders
      reach peak bone accretion during the pubertal years, though males develop a
      greater skeletal mass. Body proportions and fat distribution change during the
      pubertal years as well, with males assuming a more android body shape and females
      assuming a more gynecoid shape. Pubertal body composition may predict adult body
      composition and affects both pubertal timing and future health. SUMMARY: Sexual
      dimorphism exists to a small degree at birth, but striking differences develop
      during the pubertal years. The development of this dimorphism in body composition
      is largely regulated by endocrine factors, with critical roles played by growth
      hormone and gonadal steroids. It is important for clinicians and researchers to
      know the normal changes in order to address pathologic findings in disease
      states.

PMID- 19115521
TI  - The influence of endocrine disruptors on pubertal timing.
AB  - PURPOSE OF REVIEW: Overview of the effects of endocrine disruptors on pubertal
      timing. RECENT FINDINGS: Epidemiologic studies in humans support animal data
      demonstrating that exposures to endocrine-disrupting compounds have pronounced
      effects on pubertal timing and that the timing of endocrine-disrupting compound
      exposure and the specific agent causes different outcomes. Recent studies confirm
      subtle effects of lead, dioxins, and phytoestrogens on delaying onset of puberty
      and demonstrate an association of phthalates and polychlorinated biphenyls with
      earlier breast development and menarche, respectively. These studies, however,
      are complicated by mixed exposures of compounds which individually may have
      opposing actions on the reproductive axis. SUMMARY: Animal and human data confirm
      perturbations in pubertal onset with exposures to endocrine-disrupting compounds.

PMID- 19115523
TI  - Regulation and signaling of human bombesin receptors and their  biological
      effects.
AB  - PURPOSE OF REVIEW: This review will highlight recent advances in the
      understanding of molecular mechanisms by which mammalian bombesin receptors are
      regulated and which intracellular signaling pathways have been characterized to
      mediate agonist-dependent receptor biological effects. RECENT FINDINGS: Mammalian
      bombesin receptors have been demonstrated to be involved in a larger array of
      physiological and pathophysiological conditions than previously reported.
      Pharmacological experiments in vitro and in vivo as well as utilization of
      animals genetically deficient of the gastrin-releasing peptide receptor
      demonstrated roles in memory and fear behavior, lung development and injury,
      small intestinal cell repair, autocrine tumor growth, and mediating signals for
      pruritus and penile reflexes. Intracellular signaling studies predominantly of
      the gastrin-releasing peptide receptor owing to its frequent overexpression in
      some human malignancies showed that PI3 kinase activation is an important
      mechanism of cell proliferation. Tumor cell treatment including gastrin-releasing
      peptide receptor antagonists combined with inhibition of epidermal growth factor
      receptor resulted in an additive effect on blocking cell proliferation. Novel
      molecular mechanisms of the orphan bombesin receptor subtype-3 and gastrin
      releasing peptide receptor gene regulation have been elucidated. SUMMARY:
      Inhibition of gastrin-releasing peptide receptor signaling in human malignancies
      represents an attractive target for pharmacological treatment. Novel functions of
      bombesin related peptides have been identified including processes in the central
      nervous system, lung and intestinal tract.

PMID- 19115522
TI  - Serotonin in the gastrointestinal tract.
AB  - PURPOSE OF REVIEW: To assess the role of serotonin and its control in the
      manifestations and treatment of lower functional gastrointestinal disorders.
      RECENT FINDINGS: Recent literature has explored several novel concepts in the
      association of serotonin and symptoms, alterations in tissue levels of serotonin
      and its reuptake protein, aspects of the genetic determinants of serotonergic
      function (particularly 5-HTTLPR) and its relationship to gastrointestinal motor
      and sensory functions, and novel serotonergic agents used in therapy of lower
      functional gastrointestinal disorders. The most consistent findings are the
      increase in plasma 5-hydroxytryptamine (5-HT) in diarrheal diseases and reduction
      in constipation. The serotonin transporter in platelets has an impact on the
      circulating level of 5-HT. Meta-analysis shows that 5-HTTLPR genotype is not
      significantly associated with irritable bowel syndrome in Whites or Asians. New 5
      HT3 antagonists and 5-HT4 agonists are efficacious and promise to provide relief
      for patients if they can pass regulatory hurdles. SUMMARY: Although the most
      relevant implication for clinical practice remains the evidence that serotonergic
      agents are efficacious in the treatment of chronic constipation, chronic diarrhea
      and irritable bowel syndrome, the role of genetic control of 5-HT and its
      receptors is the subject of ongoing research, and is likely to enhance
      understanding of the mechanisms and treatment of these diseases.

PMID- 19115524
TI  - Genetics and molecular pathology of neuroendocrine  gastrointestinal and
      pancreatic tumors (gastroenteropancreatic  neuroendocrine tumors).
AB  - PURPOSE OF REVIEW: Gastrointestinal and pancreatic neuroendocrine tumors (GEP
      NETs) originate from cells of the diffuse endocrine system. Most GEP-NETs are
      sporadic, however, some of them, especially pancreatic endocrine tumors, may
      occur as part of familial syndromes. The genetic and molecular pathology of
      neuroendocrine tumor development is incomplete and remains largely unknown.
      However, the WHO classification introduced in clinical practice will give more
      insight into genetic and molecular changes related to tumor subtypes. RECENT
      FINDINGS: In sporadic endocrine pancreatic tumors, losses of chromosome 1 and 11q
      as well as gain on 9q appear to be early invents in development of pancreatic
      tumors because they are already present in small tumors. Multiple genetic defects
      may accumulate with time and result in pancreatic neuroendocrine tumor
      progression and malignancy. Gastrointestinal endocrine tumors (carcinoids) show
      predominantly genetic alterations concentrated on chromosome 18. There are losses
      of the entire chromosome as well as smaller deletions. The most frequently
      reported mutated gene in gastrointestinal neuroendocrine tumors is b-catenin.
      Overexpression of cyclin D1 and cMyc has also been reported. Recently, a set of
      genes NAP1L1, MAGE-2D and MTA1 has been correlated with malignant behavior of
      small intestinal carcinoids. SUMMARY: Molecular profiling of GEP-NETs
      demonstrates that pancreatic endocrine tumors and gastrointestinal neuroendocrine
      tumors (carcinoids) display different genetic changes and should, therefore, be
      considered to be different tumor entities; thereby, also differently managed
      clinically. Although the number of genetic changes is higher in malignant tumors,
      we are still far away from defining a malignant profile in GEP-NETs.

PMID- 19115525
TI  - Abstracts from the 1st Annual Meeting of the Diabetes and Cardiovascular Disease
      EASD Study Group (D&CVD), 21-23 November 2008, Torino, Italy.

PMID- 19115527
TI  - Posttraumatic stress disorder. Interim final rule.
AB  - The Department of Veterans Affairs (VA) is amending its adjudication regulations
      regarding service connection for posttraumatic stress disorder (PTSD) by
      eliminating the requirement of evidence corroborating occurrence of the claimed
      in-service stressor in claims in which PTSD is diagnosed in service. This
      amendment is necessary to facilitate the proof of service connection in such
      claims. By this amendment, we intend to reduce claim-processing time for such
      claims.

PMID- 19115529
TI  - Disclosure of information to organ, tissue and eye procurement organizations.
      Final rule.
AB  - This document adopts, with changes, a Department of Veterans Affairs (VA) interim
      final rule that implemented provisions of the Veterans Benefits, Health Care, and
      Information Technology Act of 2006 concerning disclosure of information to organ,
      tissue and eye procurement organizations. The regulation will provide authority
      for VA to provide individually-identifiable VA medical records of veterans or
      dependents of veterans who are deceased or whose death is imminent to
      representatives of organ procurement organizations, eye banks, and tissue banks
      to determine whether the patients are suitable potential donors. This document
      modifies the interim final rule to clarify the definition of "near death" and to
      correct a grammatical error in the definition of "procurement organization." This
      document also clarifies that eye bank and tissue bank registration with FDA must
      have an active status.

PMID- 19115530
TI  - Elimination of co-payment for weight management counseling.
AB  - The Department of Veterans Affairs (VA) published a direct final rule amending
      our medical regulations to designate weight management counseling (individual and
      group sessions) as a service that is not subject to VA's co-payment requirements.
      VA received no significant adverse comments concerning this rule or its companion
      substantially identical proposed rule published on the same date. This document
      confirms that the direct final rule became effective on June 16, 2008. In a
      companion document in this issue of the Federal Register, we are withdrawing as
      unnecessary that proposed rule.

PMID- 19115531
TI  - "Drunk and riotous in Pontypridd": women, the police courts and the press in
      South Wales coalfield society, 1899-1914.

PMID- 19115532
TI  - Civilian Health and Medical Program of the Department of Veterans Affairs
      (CHAMPVA): expansion of benefit coverage for prostheses and enuretic (bed
      wetting) devices; miscellaneous provisions. Final rule.
AB  - This document adopts a final rule amending the Department of Veterans Affairs
      (VA) medical regulations for the Civilian Health and Medical Program of the
      Department of Veterans Affairs (CHAMPVA) to expand benefits by covering any non
      dental prostheses determined medically necessary for the treatment of certain
      medical conditions and by removing the exclusion from coverage of enuretic (bed
      wetting) devices. In addition, this final rule makes changes in delegations of
      authority, technical changes, and nonsubstantive changes for purposes of clarity
      in VA's regulations governing CHAMPVA.

PMID- 19115533
TI  - Board of Veterans' Appeals: expedited claims adjudication initiative--pilot
      program. Final rule.
AB  - The Department of Veterans Affairs (VA) is launching an initiative for
      accelerated claims and appeals processing at four VA facilities, based on
      voluntary participation by eligible claimants. The purpose of this initiative is
      to determine whether VA can expedite the processing of claims and appeals by
      obtaining claimants' waivers of certain statutory and regulatory response
      periods, and by utilizing the Board of Veterans' Appeals' (Board or BVA)
      statutory authority to pre-screen cases. VA's responsibility to fully develop and
      decide cases in a fair, accurate, and non-adversarial manner remains unchanged
      under this initiative. If this initiative is successful at the four trial sites,
      the data obtained may provide a basis for expanding some, or all, of the program
      nationwide, and ultimately help accelerate the processing of all claims and
      appeals. The parameters of the initiative are set forth in these regulations.

PMID- 19115534
TI  - "A status too onerous to bear": Merthyr's struggle for civic survival, 1926-36.

PMID- 19115535
TI  - Hospital provision, charity and public responsibility in Edwardian Pontypridd.

PMID- 19115536
TI  - Democracy and its limits: gender and rights in the Czech lands, 1918-1938.

PMID- 19115538
TI  - Interpreting early modern woman abuse: the case of Anne Dormer.

PMID- 19115537
TI  - The study of the Armenian crisis of the late Ottoman Empire, or, "seizing the
      document by the throat".

PMID- 19115539
TI  - Ethics of African tradition: prescription of a dress code in Malawi, 1965-1973.

PMID- 19115540
TI  - A descriptive analysis of the food crisis in Malawi.

PMID- 19115541
TI  - [Standardization of anesthetic equipment].

PMID- 19115542
TI  - [Metabolic syndrome and risk factors associated with life style among adolescents
      in a city in Argentina, 2005].
AB  - OBJECTIVES: To determine the prevalence of metabolic syndrome among adolescents
      in a city in Argentina and to establish its association with certain risk factors
      linked to life style. METHODS: Cross-sectional study of a representative sample
      of 532 middle and high school students from 11-20 years of age (mean: 15.3 years;
      females: 60%) in the city of Posadas, province of Misiones, Argentina, from July
      October 2005. Surveys were conducted of individuals' dietary habits,
      anthropometric measurements, sedentary levels, blood pressure readings, and
      laboratory results. Metabolic syndrome was diagnosed if three or more of the
      following conditions were present: fasting glucose > or = 110 mg/dL;
      triglycerides > or = 110 mg/dL; HDL cholesterol < or = 40 mg/dL; arterial
      systolic or diastolic pressure > 90th percentile; and waist circumference > 90th
      percentile. RESULTS: The prevalence of metabolic syndrome was 4.5%; significantly
      higher among males than among females (7.5% vs. 2.5%; P = 0.006) and among the 15
      20 year old age group than among the 11-14 year old group (6.3% vs. 2.5%; P =
      0.037). Of the adolescents, 44.7% had one or more components of metabolic
      syndrome. The risk of metabolic syndrome among obese adolescents was elevated
      (odds ratio = 119.73; 95% confidence interval: 27.6-519.41). Dietary habits and
      frequency of food consumption were similar among students with and without
      metabolic syndrome; however, the first group consumed fattening foods more
      frequently. Of all the adolescents in the sample, 84.8% were sedentary (100% of
      those with metabolic syndrome). CONCLUSIONS: In the city of Posadas, some 1 400
      students suffer from metabolic syndrome and about 13 000 have at least one
      metabolic syndrome component. Joint efforts by the state government and the
      community are needed to change dietary habits and increase physical activity,
      mainly among boys, those 15-20 years of age, and the obese, to reverse the
      situation and reduce the morbidity/mortality that results from metabolic
      syndrome.

PMID- 19115543
TI  - Impact of Haemophilus influenzae type b conjugate vaccine on bacterial meningitis
      in the Dominican Republic.
AB  - OBJECTIVES: Widespread use of Haemophilus influenzae type b (Hib) vaccines has
      dramatically reduced the burden of Hib disease throughout the Americas. Few
      studies have evaluated the impact of Hib vaccination on non-culture-confirmed
      disease. This study analyzed trends in probable bacterial meningitis before and
      after the introduction of Hib vaccine in the Dominican Republic and estimated
      vaccine effectiveness against Hib meningitis. METHODS: Meningitis cases among
      children < 5 years of age were identified from admission records of the main
      pediatric hospital in Santo Domingo during 1998-2004. Laboratory criteria were
      used to classify meningitis cases with probable bacterial etiology; confirmed
      cases had positive bacterial culture or antigen detection in cerebrospinal fluid.
      Cumulative incidence rates of confirmed and probable bacterial meningitis were
      calculated for children living in the National District. Confirmed cases of Hib
      meningitis were enrolled in a case-control study with age- and neighborhood
      matched control children to calculate vaccine effectiveness. RESULTS: Before
      vaccine introduction, annual rates of meningitis with probable bacterial etiology
      were 49 cases per 100 000 children < 5 years old; Hib accounted for 60% of
      confirmed bacterial cases. During 2002-2004, after vaccine introduction, annual
      rates of probable bacterial meningitis were 65% lower at 16 cases per 100 000,
      and Hib accounted for 26% of confirmed cases. Rates of Hib meningitis and
      probable bacterial meningitis with no determined etiology declined by 13 and 17
      cases per 100 000, respectively. CONCLUSIONS: Introduction of Hib vaccine
      substantially reduced the incidence of confirmed and probable bacterial
      meningitis in the Dominican Republic. The estimated impact of Hib vaccination was
      twice as great when non-culture-confirmed disease was included.

PMID- 19115544
TI  - Prevalence of lifestyle-related cardiovascular risk factors in Peru: the
      PREVENCION study.
AB  - OBJECTIVES: To estimate the prevalence of lifestyle-related cardiovascular risk
      factors in the adult population of Arequipa, the second largest city in Peru.
      METHODS: The prevalence and patterns of smoking, alcohol drinking, lack of
      physical activity, high-fat diet, and low fruit and vegetable intake were
      evaluated among 1 878 subjects (867 men and 1 011 women) in a population-based
      study. RESULTS: The age-standardized prevalence of current smoking, former
      smoking, and never smoking were 21.6%, 14.3%, and 64.1%, respectively. The
      prevalence of current smoking was significantly higher in men than women (31.1%
      vs. 12.1%; P < 0.01). The prevalence of current alcohol use was 37.7% and
      significantly higher in men than women (55.5% vs. 19.7%; P < 0.01). Similarly,
      the prevalence of binge drinking was 21.2%, and the percentage of men who binge
      drink (36.1%) was significantly higher than for women (6.4%; P < 0.01). The vast
      majority of alcohol drinkers reported a pattern of alcohol consumption mainly on
      weekends and holidays rather than regular drinking with meals during the week.
      The proportion of insufficiently active people was 57.6% and was significantly
      higher in women than men (63.3% vs. 51.9%; P < 0.01). Overall, 42.0% of adults
      reported consuming high-fat diets, 34.5% reported low fruit intake, and 33.3%
      reported low vegetable intake. CONCLUSIONS: The high prevalence of lifestyle
      related cardiovascular risk factors found in this Andean population is of
      concern. Preventive programs are urgently needed to deal with this growing
      problem.

PMID- 19115545
TI  - [Home care's contribution to alternative health care networks:
      deinstitutionalization and transformation of practices].
AB  - OBJECTIVE: To identify state-of-the-art home care within Brazil's public health
      system, evaluate its potential for improving the comprehensiveness and
      humanization of care, and identify areas for expanding this care modality.
      METHODS: Seven home care initiatives were examined and cases were analyzed
      through interviews with five municipal services managers, seven service
      coordinators, all home-care team members, and with the service recipients, as
      well as the family members of the 27 cases selected. All of the interviews were
      recorded and transcribed. We also analyzed documents created by the home care
      services (policy manuals, management reports, evaluation reports, and care
      protocols), observed each team providing care (at least once for each of the
      seven service types), and analyzed the selected cases. RESULTS: The following
      types of home care were identified: palliative, AIDS, skin lesions/wounds,
      premature infant, bedridden patient, and supplemental intravenous antibiotic
      therapy for acute infection. The following positive aspects should be
      highlighted: the quality and humanization of care, team work, the bond developed
      with patients and family, the sense of responsibility taken on by the health
      workers, and the effective participation of caretakers and families in carrying
      out therapy plans. CONCLUSION: The initiatives examined show that home care is
      possible even in economically disadvantaged environments and that it may
      effectively contribute to providing integrated and continued care. Home care
      should be expanded in the context of the public health system.

PMID- 19115546
TI  - [Impact of rotavirus vaccine introduction on hospital admissions for severe acute
      gastroenteritis at the Children's Hospital in Panama City].
AB  - OBJECTIVES: To determine if infant rotavirus vaccination in Panama has reduced
      the rate of hospital admission for gastroenteritis among children under 5 years
      of age. METHODS: An observational, cross-sectional study of two time periods: 1
      January-31 August 2005 (prior to initiating rotavirus vaccination) and 1 January
      31 August 2007 (one year after introducing rotavirus vaccination). All the
      children from 2 months-5 years of age admitted with a diagnosis of acute
      gastroenteritis to the short-stay gastroenteritis area of the Children's Hospital
      in Panama City, Panama, were studied. The variables were: number of
      gastroenteritis episodes; number of cases admitted for severe acute
      gastroenteritis; number of days hospitalized; and antibiotics treatment for each
      of the two age groups (2 months-1 year and > 1-5 years). The relative risk (RR)
      was calculated with a 95% confidence interval (95% CI) and a significance level
      of P < or = 0.05. RESULTS: There was a total of 1 240 episodes of severe acute
      gastroenteritis in 1 222 children. No significant differences were found between
      the two study periods regarding the number of complications (P = 0.92) and deaths
      (P = 1.00). Although there were more episodes of severe acute gastroenteritis
      after initiating vaccination against human rotavirus than there were in the
      period prior, the difference was not statistically significant (RR = 1.12; 95%
      CI: 087-1.44; P = 0.39). There were no significant differences found in the
      length of hospital stay by age groups studied in each time period. The percent of
      cases treated with antibiotics was similar in both study periods (29.7% versus
      25.2%; P = 0.08). CONCLUSIONS: The introduction of infant rotavirus vaccination
      was not found to lead to a significant reduction in hospital admission rates for
      gastroenteritis among children less than 5 years of age. Significant changes in
      morbidity and in antibiotics use were not found after the introduction of the
      vaccine.

PMID- 19115547
TI  - Device-associated infection rates in intensive care units of Brazilian hospitals:
      findings of the International Nosocomial Infection Control Consortium.
AB  - OBJECTIVES: To measure device-associated infection (DAI) rates, microbiological
      profiles, bacterial resistance, extra length of stay, and attributable mortality
      in intensive care units (ICUs) in three Brazilian hospitals that are members of
      the International Nosocomial Infection Control Consortium (INICC). METHODS:
      Prospective cohort surveillance of DAIs was conducted in five ICUs in three city
      hospitals in Brazil by applying the definitions of the U.S. Centers for Disease
      Control and Prevention National Nosocomial Infections Surveillance System (CDC
      NNIS). RESULTS: Between April 2003 and February 2006, 1 031 patients hospitalized
      in five ICUs for an aggregate 10 293 days acquired 307 DAIs, a rate of 29.8% or
      29.8 DAIs per 1 000 ICU-days. The ventilator-associated pneumonia (VAP) rate was
      20.9 per 1 000 ventilator-days; the rate for central venous catheter-associated
      bloodstream infections (CVC-BSI) was 9.1 per 1 000 catheter-days; and the rate
      for catheter-associated urinary tract infections (CAUTI) was 9.6 per 1 000
      catheter-days. Ninety-five percent of all Staphylococcus aureus DAIs were caused
      by methicillin-resistant strains. Infections caused by Enterobacteriaceae were
      resistant to ceftriaxone in 96.7% of cases, resistant to ceftazidime in 79.3% of
      cases, and resistant to piperacillin-tazobactam in 85.7% of cases. Pseudomonas
      aeruginosa DAIs were resistant to ciprofloxacin in 71.3% of cases, resistant to
      ceftazidime in 75.5% of cases, and resistant to imipenem in 27.7% of cases.
      Patients with DAIs in the ICUs of the hospitals included in this study presented
      extra mortality rates of 15.3% (RR 1.79, P = 0.0149) for VAP, 27.8% (RR 2.44, P =
      0.0004) for CVC-BSI, and 10.7% (RR 1.56, P = 0.2875) for CAUTI. CONCLUSION: The
      DAI rates were high in the ICUs of the Brazilian hospitals included in this
      study. Patient safety can be improved through the implementation of an active
      infection control program comprising surveillance of DAIs and infection
      prevention guidelines. These actions should become a priority in every country.

PMID- 19115548
TI  - Economic value of disability-adjusted life years lost to violence: estimates for
      WHO Member States.
AB  - Violence is an important public health challenge with substantial economic
      consequences for the affected individuals, families, and communities. Using data
      from the World Health Organization (WHO) and the World Bank, the economic value
      of disability-adjusted life years (DALYs) lost due to violence in 2002 was
      estimated for WHO Member States and presented as a percentage of gross domestic
      product (GDP). Results indicated an estimated 48.4 million DALYs were lost as a
      result of 1.6 million deaths due to violence in 2002, for a total estimated
      economic value of US$ 151 billion (in constant US$ for the year 2000). Expressed
      as a percentage of GDP, the economic value of DALYs lost due to violence ranged
      from 0.04% to 5.1% across the 193 Member States. Much more is needed in terms of
      quantifying the economic burden of violence globally, particularly in low- and
      middle-income countries, where the burden of violence is greatest.

PMID- 19115549
TI  - [Commodification of health care services for development: the case of Colombia].
AB  - This is a succinct analysis of the circular relationship between health and
      development and the changes occurring over recent decades regarding health care
      services production and delivery that have resulted in a new paradigm. From the
      late 1970s through the 1980s, three major, worldwide shifts occurred that changed
      health care services in Colombia and in other Latin American countries: the
      privatization of government entities, the commodification of health care
      services, and the failure of the Soviet model. Health care system reform in
      Colombia, considered by some experts to be a model, is an example of health care
      commodification that, 15 years later, has not achieved the coverage, nor the
      equity, nor the efficiency, nor the quality, that it should have. More so than
      the market, the problem has been with the market entities that seek
      disproportionate profits. A solution for this situation is to appeal to nonprofit
      organizations for the purchase and sale of health care services.

PMID- 19115550
TI  - Community-directed risk assessment of mercury exposure: gold mining, fish, and
      unsuspected ethylmercury.

PMID- 19115551
TI  - Spread too thin: faculty perpectives about faculty-student ratios in Kansas.

PMID- 19115552
TI  - If it is on the shelf it must be safe, right?

PMID- 19115553
TI  - Poverty, wealth and mental well being.

PMID- 19115554
TI  - Psychiatric morbidity in two urban communities in Nigeria.
AB  - BACKGROUND: There is a welter of evidence for an inverse relationship between
      socio-economic status (SES) and mental health. The relationship is grossly under
      researched in the developing countries. OBJECTIVE: To ascertain rates of gross
      psychiatric morbidity and some demographic correlations in two communities with
      different socio-economic standards. DESIGN: A cross-sectional community based
      study. SUBJECTS: Random samples of two socio-economically dissimilar communities
      (N1 = 189, N2 = 148) were assessed for psychiatric morbidity. RESULTS: Rates of
      psychiatric morbidity obtained for the lower status community (Ajegunle) and the
      higher status community (Victoria Island/Ikoyi) on the GHQ-12 were 26.5 and 14.2
      respectively and the corresponding figures on the SRQ (non-psychosis) were 41.8
      and 18.2 and on the SRQ (psychosis) 61.5 and 31.7. A large number of positive
      socio-demographic correlations between cases and non-cases were obtained on SRQ
      and GHQ-12 in both communities. Family history of psychiatric illness
      significantly differentiates cases from non-cases on all measures of morbidity.
      CONCLUSION: The socio-economic inequality demonstrated should be minimised by
      evolving a social welfare policy in Nigeria and other developing countries that
      is responsive to the survival needs of the populace and ensures equitable
      distribution of resources across socio-economic strata. There is dire need for
      further research into the complex bearings of the link between social status and
      psychological wellness in the developing world.

PMID- 19115555
TI  - Nutritional and oral health status of an elderly population in Nairobi.
AB  - OBJECTIVE: To determine the nutrition and oral health status of elderly persons
      in Nairobi, Kenya. DESIGN: A cross-sectional study. SETTING: Households in
      Dagoretti Division of Nairobi. SUBJECTS: Two hundred and eighty nine persons
      (29.8% males and 70.2% females) aged 45 years and above were assessed. RESULTS:
      The level of malnutrition using the mid upper arm circumference was 18.8% while
      by body mass index was 11.4%. Of the population assessed, 46.4% had normal
      nutritional status while 40.9% were overweight, with more females (48.0%) than
      males (25.9%) being overweight. The study established that many of the elderly
      persons suffered from dental problems, especially periodontitis with 89.9% having
      dental plaque, calculus 85.6%, gingival recession 82.5% and bleeding gums 77.4%.
      The decayed index missing and filled teeth, was 7.173 with 19.7% caries free,
      51.9% reported tooth mobility and edentulousness was common. CONCLUSIONS: Under
      nutrition, obesity and dental problems are issues of concern among the elderly.
      There is need to develop policies that will look into the nutrition and dental
      health of the elderly in order to improve their welfare.

PMID- 19115556
TI  - Nutrition and public hygiene among children under five years of age in Mukuru
      slums of Makadara Division, Nairobi.
AB  - OBJECTIVE: To determine the relationship between sanitation and malnutrition
      among children below five years. DESIGN: A random sampling followed by an
      experimental design on microbiological analysis of food and water samples.
      SETTING: Mukuru slums of Makadara division in Nairobi City. SUBJECTS: Eighty food
      and thirty water samples from households within the study area were used.
      RESULTS: Poor food and personal hygiene were observed within the households in
      the study area. Most of the respondents did not practice hygienic methods during
      food handling such as washing hands and vegetables before preparation. Food
      especially the leftovers was served at ambient temperatures. Sneezing and
      coughing over food during preparation were also a common practice which exposed
      consumers to contamination, Garbage disposal and proper drainage were also poor
      deepening on the sanitation problem. Microbiological analysis of water and food
      revealed that food and water quality were poor due to the high coliform counts
      and confirmed presence of Escherichia coli (E-coli) and Salmonella spp. pathogens
      which are known causes of diarrhoea in children under five years of age.
      CONCLUSION: Poor hygienic and unsanitary practices are major causes of diarrhoea,
      hence malnutrition in crowded Mukuru slums of Nairobi City.

PMID- 19115557
TI  - Emergency resection of sigmoid volvulus.
AB  - OBJECTIVES: To determine the outcome of emergency resection of sigmoid volvulus
      and to determine the factors associated with adverse outcome. DESIGN:
      Retrospective case series review. SETTING: Moi Teaching and Referral Hospital
      (MTRH), Eldoret, Kenya. SUBJECTS: All cases of sigmoid volvulus operated at MTRH
      during the six years period between year 2000-2005. MAIN OUTCOME MEASURES:
      Mortality rate; morbidity rate; and duration of hospital stay. RESULTS: Ninety
      two case files were analysed. Sigmoid volvulus accounted for 14.1% of all cases
      of intestinal obstruction and 80% of large gut obstruction. The mean age was 47.3
      years and the median was 50 years. The range was 16 to 86 years. The male to
      female ratio was 29.3:1. Mortality was three (3.3%) cases and the morbidity was
      20 (21.7%) cases. The mean duration of hospital stay was 11.8 days. Inadequate
      intravenous fluid therapy had a statistically significant adverse effect on
      outcome in this study. The yearly outcome remained unchanged during the six years
      of the study. CONCLUSIONS: Emergency resection in cases with a viable colon had a
      similar outcome to the traditional standard treatment by emergency endoscopic
      derotation followed by semi-elective or elective resection. The overall outcome
      was comparable to global standards. Inadequate postoperative intravenous fluid
      therapy significantly affected the outcome.

PMID- 19115558
TI  - Demographic study of nasopharyngeal carcinoma in a hospital setting.
AB  - OBJECTIVES: To highlight demographic pattern of nasopharyngeal carcinoma and
      determine mode and stage of presentation. DESIGN: Prospective analytical study.
      SETTING: Kenyatta National Hospital (KNH)/University of Nairobi, Kenya. SUBJECTS:
      One hundred and twenty five patients seen at the ENT department of KNH. These
      were either referred from other peripheral hospitals or first seen at KNH and
      satisfied the inclusion criteria. Patients with open neck biopsy were excluded
      (among other criteria). RESULTS: Age range of the patients was 13-85 years. Male:
      Female ratio was 2.2:1 with the highest frequency in the 31-40 years. Most
      patients presented in late disease (stages III and IV) which carry a poor
      prognosis. Majority of the patients had neck swelling as the first symptom
      followed by nose blockage. Several patients referred from peripheral major
      hospitals and open neck biopsy. Majority of the patients seen were from poor
      social-economic background. CONCLUSION: Nasopharyngeal carcinoma is a common
      malignancy at KNH. Diagnosis is usually made in late stages of the disease when
      prognosis after full treatment is poor. There is need to make early diagnosis by
      heightening the index of suspicion among health professionals and probably health
      education in the community on the need to seek treatment for persistent neck
      masses.

PMID- 19115560
TI  - What is Alpha Omega?

PMID- 19115559
TI  - Hereditary haemorrhagic telangiectasia in a black adult male: case report.
AB  - Hereditary haemorrhagic telangiectasia, (HHT) or Rendu-Osler-Weber disease is a
      genetic autosomal dominant disorder that is characterised by telangiectasias,
      (small vascular malformations), in mucocutaneous tissues and arterial venous
      malformations, (AVMs), in various internal organs. Although HHT is relatively
      common in whites, the disorder has been reported to be rare in people of black
      African descent. Majority of HHT patients present with recurrent epistaxis, which
      in a significant proportion of patients is severe, warranting repeated blood
      transfusions and iron supplementation. Telangiectasias are most frequent on the
      tongue, hands, nose, lips and the gastrointestinal tract (GIT). AVMs occur in
      internal organs, particularly the lungs, brain, and the liver. Early and correct
      diagnosis of HHT is crucial as patients derive benefit from certain specific
      treatment modalities. Besides, AVMs which occur in various organs pose serious
      complications that may lead to death and therefore require early detection. We
      report a 55 year old black African male with HHT who presented with severe
      recurrent epistaxis and haematochezia leading to severe anaemia requiring
      repeated blood transfusions. His son, daughter and a maternal uncle experience
      milder recurrent epistaxis. The management of this patient and a brief review of
      the clinical features and management of HHT is presented. Our aim is to raise
      awareness of the occurrence of HHT in Kenya, in order to enhance early diagnosis
      and appropriate management.

PMID- 19115561
TI  - Techsthetics--the marriage of technology and esthetics.

PMID- 19115562
TI  - Extreme dental makeovers without extreme tooth reduction.

PMID- 19115563
TI  - Esthetic dentistry-2008.
AB  - The many procedures included in esthetic dentistry are dominant in many dental
      practices. The trend will continue until many dental practices will be primarily
      oriented toward esthetic procedures. Overall, the movement toward major
      involvement with esthetic dentistry has been good. Caution is advised to ensure
      that patients are provided with informed consent before proceeding with esthetic
      procedures and that they are not overtreated.

PMID- 19115564
TI  - Objectives for highly successful practices: the Levin Group method.

PMID- 19115565
TI  - Keys & pathways for success in dentistry.

PMID- 19115566
TI  - Diets--let's clear the deck.

PMID- 19115568
TI  - Alpha Omega dental fraternity marks centennial.

PMID- 19115567
TI  - A historic perspective of Alpha Omega and its first dental school.

PMID- 19115569
TI  - Highlights of the first 100 years of Alpha Omega.

PMID- 19115570
TI  - History of the Alpha Omega Foundation.

PMID- 19115571
TI  - [Hungarian psychiatry today. Introduction].

PMID- 19115572
TI  - [Activities of the Awakenings Foundation and the Community Mental Health Centre
      of Semmelweis University of Medicine].

PMID- 19115573
TI  - [Activities and practice at the Mental Health Centre in Szekesfehervar, Hungary].

PMID- 19115574
TI  - [Vocational rehabilitation. Experiences with the mentoring program in psychiatric
      care in Kecskemet, Hungary].

PMID- 19115575
TI  - [Innovative practices in Hungarian psychiatry--the example of Szigetvar,
      Hungary].

PMID- 19115576
TI  - [Programs for prevention of depression and suicide in Kiskunhalas, Hungary].

PMID- 19115577
TI  - [A model program for consultation and liaison in psychiatry. Introduction of the
      Konzultacio Foundation].

PMID- 19115578
TI  - [Experience with the Hungarian program of the European Association Against
      Depression].

PMID- 19115579
TI  - [Psychotherapy and psychosocial care for refugees].

PMID- 19115580
TI  - [Innovation of the Memory Foundation: day centre for people with dementia].

PMID- 19115581
TI  - [Community psychiatry model in Szolnok (Hungary) from 2003].

PMID- 19115582
TI  - [Day hospital, a community-based service].

PMID- 19115583
TI  - [Activities and practice of the mental health centre in Vac, Hungary].

PMID- 19115584
TI  - [Vadaskert Foundation Child Psychiatry Program, Hungary].

PMID- 19115585
TI  - [Innovative practices in Pomaz, Hungary 1993-2008].

PMID- 19115586
TI  - [Blue Point Drug Counseling and Outpatient Centre, Hungary].

PMID- 19115587
TI  - [Integrated Public Foundation for Drug Addiction Treatment in Baranya County,
      Hungary].

PMID- 19115589
TI  - [Introduction of the Hungarian version of Camberwell Assessment of Need (CAN-R
      hu)].

PMID- 19115588
TI  - [Assessment tools in community psychiatry, (Community Health Record, Monitoring
      Clinical Strategies)].

PMID- 19115590
TI  - [Possibilities for the reintegration of patients with schizophrenia].

PMID- 19115591
TI  - Why should doctors get involved in tobacco control?

PMID- 19115592
TI  - [Subtotal or total colectomy as surgical treatment of left-sided occlusive colon
      cancer].
AB  - INTRODUCTION: The treatment of acutely obstructed carcinoma of the left colon and
      sigmoid still represents a matter of controversy. The aim of this study was to
      assess retrospectively the results of its management by emergency subtotal or
      total colectomy with primary anastomosis. MATERIALS AND RESULTS: Sixty-seven
      patients were reviewed. There were 42 males and 25 females. The mean age was 70.5
      years (range: 26-87 years). Mean operative time was 210 minutes. There were five
      synchronous colon carcinomas (7.5%) and 23 (343%) synchronous tubulous and tubulo
      villous adenomas. No death was noted in the series. Ten postoperative
      complications (15%) occurred in nine patients including one postoperative
      peritonitis without evidence of anastomotic leak, one alithiasic cholecystitis,
      one evisceration and two intra-abdominal abscesses. The mean hospital stay was
      11.4 days. Fifty-eight patients were assessed at three and twelve months for
      functional results. No fecal incontinence was encountered. The mean number of
      bowel movements per 24 hours was 3.2 at three months and 2 at twelve months. All
      patients were satisfied with their quality of life. Twelve patients (20.7%)
      occasionally needed anti-diarrheic medications. CONCLUSION: Urgent subtotal or
      total colectomy with primary anastomosis is a safe and efficient procedure in the
      management of acutely obstructed neoplasm of the left colon. It allows to treat
      in one stage the cancer and the obstruction, bearing no mortality, acceptable
      morbidity and satisfactory postoperative functional results.

PMID- 19115593
TI  - Prevention of hypotension after spinal anesthesia for cesarean section: 6%
      hydroxyethyl starch 130/0.4 (Voluven) versus lactated Ringer's solution.
AB  - GOALS: The aim of this study is to compare the efficacy of HES 130/0.4, a new
      hydroxyethyl starch, to lactated Ringer's solution (LR) in the prevention of
      hypotension after spinal anesthesia for cesarean section (CS). MATERIAL AND
      METHODS: One hundred and twenty nonlaboring ASA I and II women having non urgent
      CS were enrolled in this prospective and randomized study. Subjects were randomly
      assigned to receive prior to anesthesia either 1 liter of LR (Gr I: n = 59) or
      500 ml of HES 130/0.4 (Gr II : n = 61). Blood pressure was measured until
      discharge from the post anesthesia care unit. Hypotension was treated with i.v.
      boluses of 3 mg of ephedrine. The nausea scale was recorded. Arterial and venous
      umbilical blood gazes were obtained. Data were compared using Mann-Whitney U-test
      and Student's t-test (p < 0.05 was significant). RESULTS: Thirty-nine patients in
      Gr II while 48 pts in Gr I experienced hypotension (p = .033). The total dose of
      ephedrine was statistically smaller in Gr II compared with Gr I (p = .001).
      Nausea after induction of spinal anesthesia occurred with similar frequency in
      both groups. Neonatal outcome was excellent and similar in both groups.
      CONCLUSION: HES 130/0.4 is more effective than LR to prevent hypotension
      following spinal anesthesia for CS; its routine use in this purpose should be
      considered.

PMID- 19115594
TI  - [Colorectal cancer in young patients: presentation, clinicopathological
      characteristics and outcome].
AB  - Previous studies have emphasized the increasing incidence of colorectal cancer
      (CCR) among young adults and suggest that they may have more aggressive disease
      and worse five-year survivals than their older counterparts. PURPOSE: Describe
      the profile of sporadic colorectal cancer in young patients focusing on its
      prevalence, clinicopathological characteristics, prognostic and survival factors.
      METHODS: Three hundred and twenty-five CCR patients were divided in two groups :
      G1 < 45 years and G2 > 45 years. RESULTS: 13.2% of patients were less than 45
      years old. A family history of a first-degree relative with colorectal cancer was
      more frequent in young patients: 44.1% vs 18.2% (p = 0.025). A significant delay
      in seeking medical care was noted in G1 patients: 29.7 weeks vs 18.6 weeks (p =
      0.01). A trend to have more aggressive stages III and IV at presentation was
      observed among young patients: 55.8% vs 48.6% (p = 0.8). Mucin-producing tumors
      were more frequently observed in G1 group: 41.9% vs 12% (p = 0.000). Mean
      survival was 76.9 months in G1 group and 91.7 months in G2 group (p = NS). Five
      year survival was 52% in G1 group and 58% in G2 group (p = 0.6). Stage for stage
      comparison was not significant in determining survival. The only independent
      factors were delay in consultation, right location of the tumor, peritoneal
      carcinomatosis, and the need for chemotherapy. CONCLUSION: This study confirms
      that colorectal cancer in young patients is frequent. Despite more frequent
      occurrence of mucin-producing tumors, age is not by itself a worse outcome
      predictor.

PMID- 19115595
TI  - Obstetric admissions to the intensive care unit: an eight-year review.
AB  - BACKGROUND: Between 0.1 and 0.9% of women develop complications of pregnancy that
      require admission to an intensive care unit (ICU). The purpose of this study was
      to review all obstetric patients admitted to the ICU over an 8-year period to
      determine the causes and outcomes of these admissions and the frequency and
      causes of maternal mortality. METHODS: This retrospective study was based on all
      obstetric patients admitted to the ICU at Hotel-Dieu de France hospital (January
      1998-December 2005). Data collected includes maternal age, gestational age,
      parity, past medical and obstetric history, delivery data, indication for ICU
      transfer, complications, ICU length of stay and death during hospitalization.
      Specific interventions were recorded. RESULTS: A total of 15 patients were
      admitted during the 8 years. The frequency of admissions was 0.24% of deliveries
      and obstetric patients represented 0.43% of all ICU admissions. The mean duration
      of stay in ICU was 7 +/- 5 days. The indications for admissions were preeclampsia
      (26.7%), sepsis (26.7%), obstetric hemorrhage (20%), cerebral encephalopathy
      (6.65%), amniotic fluid embolism (133%) and preexisting medical problems (6.65%).
      Fourteen patients (93%) had invasive monitoring and 9 patients (60%) required
      ventilation. There were five deaths, representing 333% of obstetric ICU
      admissions. CONCLUSION: The need for maternal intensive care should be one of the
      most important measure considered in the quality of maternal care. Early
      admission and management of critically ill obstetric patients in the ICU may
      decrease maternal mortality and morbidity.

PMID- 19115596
TI  - [Leptin, insulin, IGF-1 and bone mass in a group of sedentary adolescent girls].
AB  - AIM OF THE STUDY: To investigate the relationships between serum leptin, IGF-1,
      insulin and bone mineral content and density in a group of Lebanese sedentary
      adolescent girls. METHODS AND RESULTS: Twenty Lebanese sedentary adolescent girls
      participated in our study. Total body bone mineral content and density were
      measured by dual-energy X-ray absorptiometry (DEXA). In parallel, fasting leptin,
      IGF-1 and insulin concentrations were also measured. Serum leptin, IGF-1 and
      insulin concentrations were not associated with total body bone mineral content
      (BMC), total body bone mineral density (BMD) or pelvis BMD. CONCLUSION: Serum
      leptin, IGF-1 and insulin concentrations are not positive predictors of total
      body bone mineral content or density in this study group.

PMID- 19115597
TI  - Changing concepts in the management of hypertension: the role of effective and
      prompt blood pressure reduction.

PMID- 19115598
TI  - The FISH test for the diagnosis, surveillance, and prognosis of transitional cell
      carcinoma of the bladder.
AB  - BACKGROUND: A brief history of the fluorescence in situ hybridization (FISH) test
      and its use in the management of bladder tumors is outlined. METHODS & RESULTS:
      After a brief review of the subject, between 1990 and the present, including
      sensitivity and specificity studies, a referenced list of the various uses of the
      FISH test is provided. CONCLUSION: It is concluded that the FISH test has almost
      completely replaced cystoscopy, urine cytology and all other tests and markers
      for the diagnosis, surveillance, management, and prognosis of bladder tumors. It
      has completely changed and revolutionized our previous routine of managing
      bladder tumors.

PMID- 19115599
TI  - [Recurrent bruises and purpura].

PMID- 19115600
TI  - [Continuing medical education: knowledge, know-how and behavior].
AB  - The physician in training is not a student but a professional in practice. His
      medical education will be permanently confronted with experience: it is a
      permanent assessment of skills, an ongoing learning process, a "lifelong
      learning" or "continuous medical education." Medical practice requires a triple
      acquisition: a knowledge (a science), a know-how (an art), and how to do (a
      behavior). Medicine is also defined as a practice where "ethics and trust come
      together." In the present century doctors will have to fight for independence
      (every medical act is determined by science and ethics with only the patient's
      best interest in mind), to stand against the progressive erosion of
      qualifications (technocracy and medical sub-specialties), and to enhance their
      moral responsibility (scientific and social) through the development of team
      work. Medicine is more and more a scientific discipline due to the staggering
      collection of data and advances in technology. This may lead to a gradual decline
      of medical reasoning among physicians. A broad information campaign should
      address the following hot issue: doctors are bound by their conscience if not by
      law to "keep up and upgrade their knowledge." An array of incentive and training
      initiatives should therefore offset the absence of any legal obligation.
      Physicians can count on their colleagues in the Continuing Medical Education
      committee (CME) of the Order of Physicians who are working hard in order to make
      this objective a successful one.

PMID- 19115601
TI  - The nawAdir [Aphorisms] of yuHannA ibn mAsawayh.

PMID- 19115602
TI  - Chronic hepatitis C and diabetes mellitus--are they related?

PMID- 19115603
TI  - Viral resistance in HBV infection: diagnosis, implications and management.

PMID- 19115604
TI  - Oxidative stress and antioxidants in gastrointestinal diseases.

PMID- 19115605
TI  - Impact and management of hepatitis B and hepatitis C virus co-infection in HIV
      patients.
AB  - Individuals at risk of HIV are concomitantly at risk of acquiring parenterally or
      sexually transmitted viruses, including HBV and HCV. After the introduction of
      highly active antiretroviral therapy (ART), liver disease has emerged as a major
      cause of morbidity and mortality in HIV-infected persons. HBV, HCV and HIV share
      common routes of transmission, but the differential efficiency of these viruses
      to the types of exposures underlies difference in their prevalence by geographic
      region. Coinfection alters the natural history of each of these viruses in a
      peculiar way; furthermore coinfection with viral hepatitis may complicate the
      delivery of ART by increasing the risk of drug-related hepatoxicity and impacting
      the selection of specific agents (e.g., those dually active against HIV and HBV).
      The treatment of HBV in HIV co-infection is complex because the drug(s) used
      is/are associated with drug-resistance, cross-resistance, hepatotoxicity and
      suboptimal response. The aim is to achieve long-term sustained viral (HBV)
      suppression. HBV should be treated in coinfected patients with elevated HBV DNA
      or significant hepatic fibrosis (Metavir score = A2 or F2). The HBV DNA threshold
      for initiation of HBV treatment should be lower than in patients with HBV
      monoinfection. Anti HBV therapy should also be considered in those receiving ART
      irrespective of viral load and fibrosis, in order to prevent hepatitis of immune
      reconstitution. Selection of drug(s) depends on whether coinfected patients
      require treatment of only HBV or both HBV and HIV. In patients requiring only HBV
      treatment, drugs with dual antiviral activity should not be used in order to
      avoid early HIV resistance. When both HIV and HBV meet criteria for the
      treatment, agents with dual activity should be included in the anti-retroviral
      regimen. Treatment should be monitored by measuring the ALT and HBV DNA levels 3
      to 6 monthly. The required duration of HBV treatment in coinfected induviduals is
      not known and may possibly be life long. Every coinfected person with compensated
      chronic HCV should be considered for HCV treatment. However, treatment should be
      avoided in decompensated cirrhosis and in the presence of active opportunistic
      infection. In patients with CD4 counts <200 cells/il and/or plasma HIV-RNA above
      100,000 copies/mI, it may be better to consider anti HIV treatment before HCV
      treatment. The standard treatment in coinfected patients is pegylated interferon
      alfa-2a (Pegasys) or -2b (Peg-Intron) plus ribavirin for 48 weeks. Several
      studies have shown an overall sustained vwal response rate of 14% to 29% in
      genotype 1 and 53% to 73% in genotypes 2 and 3. The other concern with treatment
      is drug interaction with anti retroviral drugs necessitating avoidance of certain
      drugs from ART regimen. The coinfected persons with decompensated liver cirrhosis
      should not be denied HAART and should be evaluated for liver transplantation.
      Finally, management of patients not responding to standared therapy is not known.

PMID- 19115606
TI  - Increased prevalence of type II diabetes mellitus in hepatitis C virus infection
      in western India.
AB  - BACKGROUND: Type II diabetes mellitus (DM) has been shown as more common in
      patients with hepatitis C virus infection (HCV). Similar data from India is not
      available. METHODS: This 3-year prospective study included consecutive Indian
      patients with HCV to detect the DM. In all patients, the presence of DM, duration
      of DM, probable duration of HCV, genotype of HCV, presence of steatosis and
      presence of cirrhosis were noted. Comparable numbers of consecutive patients with
      hepatitis B virus infection (HBV) and irritable bowel syndrome (IBS) were
      analysed for the presence of DM. RESULTS: A total of 200 patients with HCV were
      analysed: mean age = 45.9 +/- 9.8 years; male:female=1.3:1; genotype distribution
      (in 80 patients which included 17 patients of DM)--genotype 3 in 47 (58%),
      genotype 1 in 31 (39%) and genotype 2 in 2(3%) patients; probable duration
      (unknown in 40 patients) of HCV = 12.8 +/- 8.2 years; steatosis in 55(27.5%)
      patients; cirrhosis in 88 (44%) patients. Of these 200 patients, DM was present
      in 44(22%) patients with mean duration of DM of 6.1 +/- 2.3 years. HCV preceded
      DM in 29 patients by 10.8 +/- 2.3 years. Among HCV with genotype 3, DM was
      present in 11(23.4%) patients and with genotype 1, DM was present in 6(19.3%)
      patients. In patients with DM, cirrhosis and steatosis were present in 28(63.6%)
      and 20(45.4%) patients, respectively, as compared to 60 (38.4%) and 35 (22.4%)
      patients without DM. There was significantly lower presence of DM, 24 (12%) and
      19 (9.5%), in 200 patients of HBV and 200 patients of IBS, respectively.
      CONCLUSION: There is increased prevalence of DM in patients with HCV. HCV
      precedes the development of DM by a decade.

PMID- 19115607
TI  - Effect of different doses of carotenoids in isoniazid-rifampicin induced
      hepatotoxicity in rats.
AB  - AIM: Isoniazid (INH) and Rifampicin (RIF) are hepatotoxic drugs. Oxidative stress
      has been reported as one of the mechanisms of INH+RIF induced hepatotoxicity.
      METHODS: Intragastric administration of INH and RIF (50 mg/kg body weight/day
      each) for 28 days in Wistar rats is hepatotoxic, indicated by raised
      transaminases and histology. Carotenoids have antioxidant properties. Therefore,
      different doses of carotenoids (2.5, 5, 10 and 20 mg/kg body weight/day) were
      administered to study the hepatoprotective effect against INH+RIF. RESULTS: The
      higher doses of carotenoids i.e.10 and 20 mg/kg body weight/day showed partial
      hepatoprotection indicated by return to normal of liver transaminase level and of
      liver histology in 33.3% of rats. There was no further protective effect seen by
      increasing the dose of carotenoids from 10 to 20 mg/kg body weight/day. Lower
      doses of carotenoids, i.e., 2.5 and 5 mg/kg body weight/day were not effective.
      CONCLUSION: Thus, a minimum dose with maximum hepatoprotection (10 mg/kg b.wt/
      day) was selected as the optimum dose in the present study. The hepatoprotective
      nature of carotenoids in INH+RIF treated rats may be attributed to their
      antioxidative property.

PMID- 19115608
TI  - HAV in Isfahan province: a population-based study.
AB  - INTRODUCTION: Hepatitis A infection is caused by the hepatitis A virus (HAV).
      Improved sanitary conditions have resulted in a significant decline in the
      incidence of hepatitis A. There is inadequate data about the epidemiology of this
      infection in Iran. Therefore, this study was carried out to evaluate the anti-HAV
      seroprevalence in Isfahan Province in Iran in 2006. METHODS: In a cross-sectional
      study, 816 subjects over 6 years from urban and rural areas of the Isfahan
      Province in 2006 using the multi-stage cluster sampling method were selected.
      Demographic data and blood samples were collected and anti-HAV antibodies were
      measured by ELISA. Chi-square, odds ratio and logistic regression tests were used
      for statistical analysis and a p value<0.05 was considered significant. RESULTS:
      The subjects of this study included 428 female and 388 male subjects. The overall
      anti-HAV seroprevalence rate was 8.33%. There were statistical differences
      between HAV seropositivity in districts of Isfahan province; the highest
      seropositivity was seen in Borkhar and Meimeh (28.6%) (p<0.001). There was no
      significant difference in HAV seropositivity between the subjects grouped
      according to demographic factors. CONCLUSION: HAV seroprevalence in Isfahan
      province is not high that can caused by improved sanitary conditions. More
      studeis in other parts of Iran are needed to set new strategy for post exposure
      prophylaxis and hepatitis A vaccination.

PMID- 19115610
TI  - Bleeding duodenal lipoma treated with endoscopic polypectomy.
AB  - Duodenal lipomas are relatively uncommon and are rarely a source of severe upper
      gastrointestinal haemorrhage. We report the case of a 70-year-old woman who
      presented with significant upper GI bleed due to a large bleeding duodenal lipoma
      that was successfully treated by endoscopic polypectomy.

PMID- 19115609
TI  - Serology of HBV and its clinical implications among Nigerian subjects.

PMID- 19115611
TI  - Biphasic multidetector CT of primary hepatic lymphoma in a patient with HIV
      infection.
AB  - Primary hepatic lymphoma (PHL) is a rare condition. It is the most common hepatic
      neoplasm in patients with acquired immune deficiency syndrome (AIDS). We report a
      case of PHL in a patient with human immunodeficiency virus (HIV) infection and
      describe the imaging findings on biphasic multidetector CT (MDCT).

PMID- 19115612
TI  - Gastric atrophy and intestinal metaplasia in a patient on long-term proton pump
      inhibitor therapy.
AB  - We report the case of a patient with gastroesophageal reflux disease who
      developed gastric atrophy and intestinal metaplasia (IM) while on 20-year
      treatment with proton pump inhibitors. This is perhaps the first report in human
      beings. A 74-year-old man, who presented with heartburn, showed abnormally high
      gastric pH (average 6.57) on 24-hour dual channel pH-metry even after
      discontinuing acid suppressive drugs for one month. No significant esophageal
      acid exposure was noted, which may be related to an impairment of the acid
      secreting capacity of the stomach (percentage time esophageal pH<4 during 24-h
      period 0.3%). Upper gastrointestinal endoscopy was normal except for the
      prominent submucosal vessels in the body and fundus suggesting gastric atrophy.
      Histopathological examination of multiple biopsies from the body and antrum of
      stomach showed signs of gastric atrophy and IM. Rapid urease test and
      histopathology of gastric biopsies were negative for Helicobacter pylori. Anti
      H.pylori IgG ELISA however, was positive. Patient was asked to stop all anti
      secretory drugs and only prokinetics were prescribed following which his symptoms
      markedly improved. On follow-up, in April 2007, he developed symptoms of
      peripheral neuropathy; serum vitamin 812 level was low. He responded to
      parenteral vitamin 812 therapy. 24-h dual channel pH-metry repeated after one and
      a half years showed persistently high gastric pH (average pH 6.76). The patient
      remained well after discontinuing proton pump inhibitors and continuing
      prokinetics and vitamin B12 injections.

PMID- 19115613
TI  - Tropical pancreatitis and fibrocalculous pancreatic diabetes--two sides of the
      same coin?
AB  - Tropical pancreatitis and fibrocalculous pancreatitic diabetes are usually
      considered two ends of the same disease although some studies suggest the
      likelihood of distinct entities. We report the occurrence of these two diseases
      in two siblings. The literature comparing the similarities and differences
      between them is briefly reviewed.

PMID- 19115614
TI  - Solitary rectal ulcer syndrome in childhood.
AB  - Solitary rectal ulcer syndrome is a rare disorder of childhood and usually goes
      unrecognised or misdiagnosed because it can mimic various other rectal entities.
      Here a 9-year old boy presented with bleeding per rectum and altered bowel
      habits. Colonoscopy revealed multiple ulcers which on histopathological
      examination showed features of SRUS with severe reactive changes of regeneration
      mimicking malignancy.

PMID- 19115615
TI  - Isolated mesenteric fibromatosis.
AB  - Fibromatosis is a rare, locally aggressive but non-metastasising fibrous mass
      often associated with familial adenomatous polyposis in Gardner's Syndrome (GS).
      Although sporadic cases occur, unlike in GS, they are predominantly extra
      abdominal. We report the case of a 40-year-old lady who underwent laparotomy for
      a large isolated abdominal mass three years after a Whipple's procedure for
      adenocarcinoma of the distal common bile duct. A spherical, football sized tumour
      was found in the jejunal mesentery. Resection of the tumour with jejunum was
      carried out. No metastasis was detected. This case is peculiar in that mesenteric
      fibromatosis occurred in a patient with prior history of periampullary carcinoma
      and without history of familial adenomatous polyposis.

PMID- 19115616
TI  - [Prevalence and control of schistosomiasis in mountainous endemic regions of
      China].

PMID- 19115617
TI  - [Spatial distribution and elimination of Schistosome japonicum intermediate hosts
      Oncomelania hupensis in mountainous regions].
AB  - OBJECTIVE: To explore the spatial distribution and elimination of Oncomelania
      hupensis in mountainous regions. METHODS: Puge County in Tezi township was
      selected as the study site and the quadratus were placed randomly to investigate
      snail. The two sods with water were selected as the sites of snail elimination.
      One sod with area of 1000 m2 and mean density of 9.88 snails/0.11 m2 was selected
      as the trial group with 'heaping' method, and the other with area of 1000 m2 and
      mean density of 9.80 snails/0.11 m2 as the control group with sprinkling method.
      The molluscacidal effect of the two methods was compared by systematic sampling
      (5 m x 5 m). The sample size was 40 quadratus. RESULTS: The snail distributed
      mainly in the sods with water, canals and farmlands. Among the three snail
      habitats, the area with snail was the most in the farmlands with relatively lower
      density of living snail; the next was the sods with water, with relatively higher
      density of living snail. Before killing snails, the rate of quadratus with snails
      was 87.50% in the trial site, and 82.50% in the control site. The mortality of
      snails was 3.89% in the trial site, and 4.16% in the control site. After three
      months, no living snails were found in the trial site, while in the control site,
      the rate of quadratus with snails (chi2 = 0.31, P > 0.05) and the mortality of
      snails (chi2 = 3.12, P > 0.05) did not decrease significantly, and the density of
      living snails only reduced by 8.88%. CONCLUSION: The 'heaping' method is an
      efficacious measure for snail control.

PMID- 19115618
TI  - [Modeling transmission dynamics and control of schistosomiasis in the mountainous
      region, Sichuan].
AB  - OBJECTIVE: To use a mathematical model and computer simulation to study
      transmission dynamics and control of schistosomiasis in mountainous regions of
      Sichuan. METHODS: Based on studies of schistosomiasis japonica transmission in 20
      villages in mountainous regions of Sichuan, a mathematical model was developed to
      characterize the impact of local environmental factors on transmission intensity.
      The model integrated site-specific factors and was calibrated to field
      epidemiological data from 3 subset villages. The dichotomic method was then used
      to predict different control measures. RESULTS: The study showed high variations
      in prevalence of infection and infection intensity across villages, ranging
      between 3%-73%, 0.1-100 epg (eggs per gram stool), respectively. Important
      factors including occupation of local residents, exposure to contaminated water,
      microclimatic characteristics were integrated in the model. The predictions of
      dichotomic models showed that continuing chemotherapy (coverage between 50%-60%)
      could reduce infection intensities to 30%-80%, but could not change local
      transmission potential; therefore, the termination of chemotherapy would be
      followed by bouncing back of transmission. Sustaining targeted environmental
      interventions through snail and parasite oval control at certain coverage (30%
      50%, respectively) could reduce the transmission to relatively stable levels. The
      model predictions showed that an integrated control (e.g., including both
      chemotherapy and environmental interventions) could suppress the transmission to
      an undetectable level even interruption of transmission between 5-10 years.
      CONCLUSION: The study demonstrated the feasibility of using a dynamic model,
      calibrated to local data, to gain insights into complicated processes underlying
      the transmission and informing site-specific control strategies.

PMID- 19115619
TI  - [Snail control by using soil pasting mixed with niclosamide].
AB  - OBJECTIVE: To evaluate the effect of snail control through soil pasting mixed
      with niclosamide. METHODS: Four sites were selected in different epidemic areas
      in Sichuan province. Soil pasting mixed with niclosamide was carried on, and the
      dosage was 0 g/m2, 4 g/m2, 6 g/m2, 8 g/m2 and 10 g/m2 respectively. The mortality
      rate of snail and the density of snail were observed after 7, 15, 30, 90 and 180
      days. RESULTS: The mortality rate of snail was more than 43.3% in blank group
      after 30 days. The mortality rate of snail was from 75.3% to 100.0% at 4 g/m2
      group after 30 days. The mortality rate of snail in 4 g/m2 group was
      significantly higher than that in the blank group (chi2 = 31.27, P < 0.05). There
      was no significant difference in the mortality rate of snail among all study
      groups (chi2 = 1.07, P > 0.05). The decrease rate of snail density was more than
      90%. The mortality rate of snail was about 30% higher in Chantu group than Qutu
      group. The unit cost of Pasting-Mixing Drug with Soil was from 5 to 7 times of
      spray method, but the total cost was similar for the. two methods at the endpoint
      of the snail control. CONCLUSION: The effect of soil pasting mixed with
      niclosamide is good, and the dosage of 4-6 g/m2 is suggested in snail control.

PMID- 19115620
TI  - [Molecular epidemiological study on the host and role of the Hantavirus and
      Orientia tsutsugamushi in the same epidemic area].
AB  - OBJECTIVE: To investigate whether Hantavirus (HV) and Orientia tsutsugamushi (
      OT) can naturally infect and coexist in their host and role. METHODS: By field
      epidemiological study, Leptotrombidium scutellare (3829) was collected and
      separated from mice(166) in epidemic areas. The cells of mites separated from
      their host and role were cultured. PCR was used to detect HV-RNA and OT-DNA in
      the cell culture. RESULTS: In 105 Apodemus agrarius, 3 HV-RNA positive, 2 OT-DNA
      positive and 2 coinfection with HV and OT were detected;in 41 Brown rattus, 2 HV
      RNA positive, 1 OT-DNA positive and 1 co-infection with HV and OT were detected.
      From 15 mites co-infected with HV and OT, 2 strains of HV pathogen, 2 strains of
      OT pathogen were separated and 1 HV and OT pathogen in the same mite were
      separate. CONCLUSION: The study demonstrates that co-infection of HV and OT did
      simultaneously exist in wild Leptotrombidium scutellare. This theory has some
      significance to the epidemic and precaution of HV and OT.

PMID- 19115621
TI  - [Sterilizing effect and mechanism of electrolyzed water].
AB  - OBJECTIVE: To study the sterilizing effect and mechanism of electrolyzed
      oxidizing water (EOW) and electrolyzed-reductive water (ERW) for Bacillus
      subtilis var. niger (ATCC9372) and Escherichia coli (8099). METHODS: The
      generations of EOW and ERW were made in the ion membrane electrolysis cell. The
      sterilization manner was the suspension quantitative germicidal test. RESULTS:
      The killing rate of EOW for Bacillus subtilis var. niger was 99.59% in 30 minutes
      and the killing logarithm value was 2.38 log cfu/ml; the killing rate of ERW for
      Bacillus subtilis var. niger was 94.62% in 60 minutes and the killing logarithm
      value was 1.27 log cfu/ml; the killing rate of ERW for Escherichia coli was 100%
      in 30 minutes and the killing logarithm value was 8.26 log cfu/ml. When the
      available chlorine content (ACC) value in EOW was 74.90 mg/L and killing time was
      30 minutes, the killing rate for Bacillus subtilis var. niger was 99.89% and the
      killing logarithm value was 2.67 log cfu/ml. When the ACC value was 6.82 mg/L,
      the killing rate for Bacillus subtilis var. niger was 83.30% and the killing
      logarithm value was 0. 78 log cfu/ml under the same time. When the oxidizing
      reductive potential (ORP) and pH values of EOW were 1138 mV and 2.24
      respectively, the killing rate for Bacillus subtilis var. niger was 99.99%. When
      the ORP and pH values of EOW were 883 mV and 5. 43 respectively, the killing rate
      of Bacillus subtilis var. niger was 99.73%. When the ORP value of ERW is -918 mV,
      the sterilizing rate for Bacillus subtilis var. niger was 94.62%; when the ORP
      value is -155 mV, the sterilizing ratio was only 40.19%. CONCLUSION: It indicates
      that the sterilizing mechanism of EOW is mainly chemical processes (ACC), while
      the physical factors are auxiliary. The sterilizing mechanism of ERW is physics
      sterilizing that the mainly factor is ORP.

PMID- 19115622
TI  - [Relationship between susceptibility of formaldehyde metabolism and genetic
      polymorphisms of ALDH2 and cytochrome P4502E1].
AB  - OBJECTIVE: To study the relationship between occupational hazard susceptibility
      of formaldehyde and genetic polymorphisms of ALDH2 and CYP2E1. METHODS: Genotypes
      of ALDH2 and CYP2E1 (Rsa I/Pst I site) of 107 subjects exposed to formaldehyde
      were determined with PCR-RFLP through testing peripheral blood lymphocytes, and
      the concentration of air formaldehyde in workplace and urine formic acid of the
      subjects were measured with HPLC. The relationship between genotypes and the
      urine formic acid increment was analyzed with nonparametric rank sum testing.
      RESULTS: The concentration of urine formic acid increment was related with ALDH2
      genotypes (chi2 = 9.241, P < 0.05), and the means of urinary formic acid of
      subjects with GG, GA, AA genotype were (15.84 +/- 6.86), (12.06 +/- 7.94) and
      (7.31 +/- 5.37) mg/g creatinine, respectively. Mann-Whitney U test showed the
      formic acid increment between allele G homozygotes and allele A homozygotes was
      significantly different (U=26, P= 0.033). Our data indicated that the
      formaldehyde metabolism of ALDH2 GG homozygotic genotype was more active than
      ALDH2 AA homozygotic genotype(the difference of the two mean rank was 13.30). But
      the polymorphism of Rsa I / Pst I site of CYP2E1 5'-franking region was not
      correlated with the concentration of urine formic acid (chi2 = 4.285, P=0.117),
      and the urinary formic acid means of subjects with C1/C1, C1/C2, C2/C2 genotype
      were (11.14 +/- 7.91), (12.13 +/- 8.16) and (16.51 -/+ 3.78) mg/g creatinine,
      respectively. By Stepwise Multiple Regression Analysis, it showed that the
      urinary formic acid increment might be influenced by FA exposure concentration
      and ALDH2 genotype, and the model's R2 was 0.196. CONCLUSION: The metabolism of
      formaldehyde in human body was related with the genotypes of ALDH2, but not with
      the CYP2E1 (Rsa I/Pst I) polymorphisms.

PMID- 19115623
TI  - [A study of reliability and validity of appraisal questionnaire (Chinese language
      version) of human immunodeficiency virus positive persons].
AB  - OBJECTIVE: To evaluate the Chinese language version of the appraisal
      questionnaire (AQ) for HIV/AIDS (HIV positive persons). METHODS: The scale was
      translated and adapted into Chinese and then reversely translated into English.
      The internal consistency reliability, structural validity, differential validity
      and predictive validity were evaluated by prevalence study in the city of
      Guangzhou. RESULTS: Cronbach's alpha coefficient achieved a value ranged from
      0.530 to 0.886, with satisfied predicted validity. The regression equation
      accounted for 24.4% of variance in anxiety, and all factors of cognition
      accounted for 11.4% of variance, among all factors, only factor one had
      significant influence on anxiety (t=3.838, P<0.001); the regression equation
      accounted for 38.6% of variance in depression, and all factors of cognition
      accounted for 26.0% of variance. Factor I and factor II had significant influence
      on depression (t=5.707, P<0.001; t = -2.876, P<0.01). The results of differential
      validity suggested the mean scores of factor III were lower in the group with
      lower education level and monthly salary. Meanwhile, the persons with monthly
      salary under 300 yuan RMB had higher mean score of factor I, and the persons with
      lower academic degree had lower mean score of factor II. The principal-components
      factor analysis yielded three factors with common factor larger than 1.0, which
      were threat, challenge and controllability; and the three factors accounted for
      62.23% of the total variance. CONCLUSION: The AQ Chinese version attained
      satisfactory reliability and validity. Even considering some essential
      explanatory words for the Chinese version, the scale might be attempted to use in
      the population with HIV in our country.

PMID- 19115624
TI  - [Epidemiological characteristics and prevention strategies of viral hepatitis in
      Chongwen District of Beijing during 1997-2006].
AB  - OBJECTIVE: To understand the epidemiological features of viral hepatitis, and
      provide scientific evidence for developing strategies for prevention and control.
      METHODS: Through descriptive epidemiological methodology, the epidemiological
      characteristics of 1121 viral hepatitis cases in Chongwen District (1997-2006)
      were studied. chi2-test was used in ratio comparison. RESULTS: There were 1121
      viral hepatitis cases occurring in the past decade, and the incidence rate was
      declining by year with the average of 27.10/ 100,000. Of which, the incidence
      rate of viral hepatitis B was the highest (13.90/ 100,000), viral hepatitis C
      (1.38/100,000) was the lowest. The proportion of viral hepatitis B was the
      highest (575, 51.29%) and viral hepatitis C (57, 5.08%) was the lowest. The
      incidence of viral hepatitis A, B and no-typing was declining year by year, while
      viral hepatitis C and E was climbing. Most viral hepatitis A and E cases occurred
      in Spring and Winter, and the difference of incidence rate between male and
      female was observed (chi2 = 188.39, P < 0.001). The findings also showed that
      viral hepatitis might occur in all kind of occupation, but most were workers
      (306, 27.3%) and officers (209, 18.64%). For the age distribution, 20 -49 years
      old group took the majority (749, 66.82%); and for the transmission route, blood
      transfusion (7.64/ 100,000) was significantly higher than fecal-oral route (3.02/
      100,000) (chi2 = 5.09, P < 0.01). CONCLUSION: It is necessary to raise and
      increase the public awareness for viral hepatitis prevention and control, and
      enhance immunization. Moreover, effective measures should be taken to the safety
      of blood and blood products, and to prevent nosocomial infection.

PMID- 19115625
TI  - [The roles of saliva testing for preventing hepatitis B virus spreading].
AB  - OBJECTIVE: To discuss the significance of testing hepatitis B virus (HBV) from
      saliva in HBV patients. METHODS: HBV DNA content in serum and saliva of 200 HBV
      patients and 20 healthy subjects were detected by fluorescence quantitative
      polymerase chain reaction. According to the serum level of HBV content, four
      groups were divided: control group A, group B negative, low virus C (1 x 10(3) -
      1 x 10(5) copies/ml) and high-group D ( > 1 x 10(5) copies/ml). The relationship
      of serum and virus content in saliva was analysed. RESULTS: Of 200 HBV cases, 180
      were found HBV DNA in serum with positive rate of 90.0%; while 145 were found HBV
      DNA in saliva with positive rate of 72.5%, and there was no significant
      difference (chi2 = 1.35, P > 0.05). The significant difference was observed in
      testing serum and saliva in Group C (100.0% vs. 38.5%; Z = 14.11, P < 0.01). In
      group D, there was no significant difference found either (100.0% vs. 83.8%; chi2
      = 1.05, P > 0.05). Group D virus serum had a high average level of (6.63 +/-
      1.55) log copies/ml virus and in the saliva had an average level of (5.21 +/-
      1.85) log copies/ml; saliva had serum viral load lower than an order of magnitude
      average. No HBV DNA was found in serum or saliva from 20 health subjects.
      CONCLUSION: When the serum contains a high content of HBV DNA virus, the content
      of saliva HBV DNA virus should be likely high, which might pose a threat of
      source of infection. A precise quantitative detection of HBV DNA in saliva might
      be used as evaluation of the level of virus in the body copy for judgment of
      infection.

PMID- 19115626
TI  - [Traumatic optic neuropathy should be managed as an ophthalmic emergency].
AB  - Traumatic optic neuropathy (TON) had an increasing tendency. The patients with
      TON had severe visual loss and poor visual outcome. It was recognized that early
      diagnosis and treatment could obtained higher visual improvement rate. The key of
      success treatment was in time. Taking TON as an emergency, quick and accurate
      clinical diagnosis, immediate CT scan on optic canal area and necessary visual
      electrophysiology check, early and rational therapy including surgery, good
      visual outcome would be obtained.

PMID- 19115627
TI  - [Problems in diagnosis and treatment of orbital foreign body--an analysis of 24
      cases].
AB  - OBJECTIVE: To evaluate the problems presented in the diagnosis and treatment of
      orbital foreign body. METHODS: This was a retrospective case series. We reviewed
      and analyzed 24 cases of orbital foreign bodies treated by us in the past 5
      years. RESULTS: Twenty four orbital foreign body cases were treated by the
      authors from May 2002 to May 2007. Eleven cases were plant foreign bodies, 6
      cases were metallic foreign bodies, 2 cases were glass foreign bodies and 5 cases
      were other types of foreign bodies. Wound cleaning operations were performed in
      18 cases. Foreign body removal surgery was performed in 12 cases. In 7 cases,
      three or more operations were undertaken. The problems presented in the diagnosis
      and treatment of orbital foreign body included: (1) History taken was inadequate
      and failed to recognize the presence of orbital foreign body. (2) The necessary
      CT examination was not performed. (3) CT films was not read correctly and failed
      to detect the orbital foreign bodies. (4) An exploration operation was not
      performed during the emergency operation and subsequent operation for draining of
      pyogenic infection. (5) Only part of the wood or plastic fragments were removed
      during the operation. (6) Foreign bodies could not be extracted or were pushed
      deeply due to unfamiliar with the structure of the orbit, lack of adequate
      surgical skills or absence of necessary instruments. (7) A second CT examination
      was not performed and foreign body was not re-localized before the second
      surgery. (8) An inappropriate anesthesia method were selected (such as using
      local anesthesia instead of general anesthesia) so that the patient could not
      stand the painful operation. CONCLUSIONS: Many problems presented in the
      diagnosis and treatment of orbital foreign body, including the handling of the
      structure of the orbit, correct reading of CT imaging and diagnosis of orbital
      foreign body, well-informed operative approach, increasing the removal of orbital
      foreign body and decreasing the complications, these should be focused by
      ophthalmic surgeons.

PMID- 19115628
TI  - [Treatment of orbital venous malformation using surgical procedure combined with
      Nd:YAG laser].
AB  - OBJECTIVE: To evaluate the security and efficacy of surgical procedure combined
      with Nd:YAG laser in the management of orbital venous malformation. METHODS: A
      total of 17 successive patients with orbital venous malformation were treated
      with surgical excision in conjunction with Nd:YAG laser from July 2003 to June
      2005. General anesthesia was performed in all patients. Appropriate approach was
      used according to the location and size of the lesion as well as its relation
      with adjacent tissues. Surgical procedure and laser coagulation were performed
      alternatively. Intermittent or continuous photocoagulation aimed at minor and
      deep lesions or large and superficial lesions was administrated, respectively,
      when indicated. Laser power of these two procedures was set at 60 to 90 J/cm2 or
      less than 100 J/cm2, respectively. Cold saline solution was used to cool the
      targeted region immediately after photocoagulation in case of damage to
      surrounding normal tissues. RESULTS: Seventeen patients were followed-up for 12
      to 26 months. Notable lesion regression was found in 15 cases and fair reduction
      of the lesion in 2 cases. Vision acuity decrease did not occur and vision acuity
      increase was found in 2 patients. Exophthalmos was completely corrected,
      enophthalmos was found in 4 patients, the movement of the eyeballs was markedly
      improved. Complications consisted of superior oblique muscle paralysis (1 case)
      and ptosis (1 case). Relapse or aggravation of residual lesion was not found
      during the whole follow-up period. CONCLUSIONS: Surgical procedure combined with
      Nd:YAG laser is a safe and effective procedure in managing patients with orbital
      venous malformation. Laser treatment can decrease the hemorrhage during
      operation, make the surgical procedure easier, reduce the risk of operation and
      improve the results of surgical treatment.

PMID- 19115629
TI  - [Diagnosis and management of orbital metastatic tumors].
AB  - OBJECTIVE: To evaluate the type, clinical features and diagnostic methods of
      orbital metastatic tumors. METHODS: In a retrospective study, the records of 30
      consecutive cases with orbital metastatic tumors as confirmed by pathologic
      examination were analyzed with special attention to the epidemiology, clinical
      manifestations and imaging findings. RESULTS: Most orbital metastatic tumors in
      China originated from the breast, followed, in order, by the lung and liver. The
      metastatic tumors of the orbit most frequently originated from the liver and lung
      in males, and from the breast and lung in females. The male or female ratio of
      patients with orbital metastasis was 1:1. The orbital metastases were more common
      in the children and the elderly. In 50% of patients, the orbital symptoms were
      the first signs of the disease. The longest course was seen in metastasis from
      the breast and the shortest from various types of blastomas. Orbital metastases
      could occur unilaterally or bilaterally. The most common symptoms of orbital
      metastatic tumors included diplopia and orbital pain. The signs included
      proptosis, limited ocular movement and increased intraorbital pressure. Based on
      the images of computed tomography or magnetic resonance imaging, orbital
      metastatic tumors could be divided into four different types according to the
      location and morphology of the tumors. Follow-up results revealed that 60% of
      orbital metastasis had poor prognosis. CONCLUSIONS: The spectrum of orbital
      metastatic tumors in China is different from that in western countries.
      Familiarity with the clinical manifestation and diagnostic methods of orbital
      metastatic tumors can be helpful to relief the ocular symptoms and prolong the
      life of patients.

PMID- 19115630
TI  - [Orbital solitary fibrous tumor: a clinicopathologic analysis].
AB  - OBJECTIVE: To study clinicopathologic features, histologic characteristics,
      differential diagnosis and the treatment of orbital solitary fibrous tumor (SFT).
      METHODS: Clinical, radiographic and pathologic findings of 6 cases of SFT were
      retrospectively analyzed. Immunohistochemistry were performed on selected
      samples. RESULTS: Four patients were males and 2 were females. Patients age
      ranged from 19- to 57-years-old. The location of the tumor was in the muscle cone
      (case 1 and case 5), medial (case 3), lateral (case 4), superior (case 2) and
      inferolateral (case 6) portion of the orbit, respectively. The presenting symptom
      was proptosis in 3 cases and was mass of subconjunctival or orbit margin in other
      3 cases. Image examination: SFT appeared as a round (case 6 showed irregular) and
      well-circumscribed parenchymatous mass that could be homogenously enhanced by
      contrast. Histologically, SFT displayed as a mass of spindle cells in an
      irregular arrangement Sometime, tumor cells could be storiform or sarciniform.
      Mitotic figures were infrequent and usually there were 0 to 3 mitotic figures per
      10 high-power fields. Hyalinization and staghornform blood vessels were
      frequently observed. SFT was immunoreactive for markers such as Vim, CD34 and
      CD99. Two cases were recurred. CONCLUSIONS: SFT is a rare orbital tumor and could
      be confused with other types of orbital tumors. This tumor can be diagnosed by
      pathological and immunocytochemical studies, these characteristics can be used to
      differentiate it from other types of orbital tumors.

PMID- 19115631
TI  - [Transcranial operation for cranio-orbital communicating tumors and its
      complications].
AB  - OBJECTIVE: To investigate the procedure of transcranial operation via pterional
      approach for cranio-orbital communicating tumors, to improve surgery skills, to
      summarize the incidence of main complications and to discuss tips for avoiding
      damage of the normal orbital tissues. METHODS: Pterional approach was adopted for
      the operation. After the medial orbital wall or lateral orbital wall was bitten
      with rongeur and the orbital roof was removed, the extraocular muscles at orbital
      apex were separated and protected. The head of condenser was used to freeze the
      tumor, and the tissue around the tumor was separated until the tumor was
      extirpated. In cases where the tumor penetrated the dura mater and invaded the
      brain, surgery was performed by neurosurgeons. RESULTS: In 37 cases, 32 cases
      undertook total resection of tumors and palliative resection was performed in 5
      cases due to severe tumor invasion of the cavernous sinus or sphenoid sinus. Of
      the 37 cases, 28 cases were benign tumors and accounted for 75.67% of total cases
      (28/37); 9 were malignant tumors and accounted for 24.32% (9/37). Pathological
      examination showed that 11 cases were meningioma which was the most common type
      of tumor and accounted for 29.73% of total cases(11/37). The most common
      complication was injury to extraocular muscles, which occurred in 21 cases and
      accounted for 56.76% of all cases (21/37). The most serious complication was
      vision loss, which occurred in 4 cases and accounted for 10.81% of all cases
      (4/37). CONCLUSIONS: Resection of cranio-orbital communicating tumors via
      pterional approach provides a wide observation field and facilities exposing
      tumors. Protecting important tissues in posterior orbital region will result in
      less postoperative complications.

PMID- 19115632
TI  - [Effects of placement of orbital implant on orbital osteocytes].
AB  - OBJECTIVE: To investigate the influence of enucleation with or without orbital
      implant on the occurrence of apoptosis of orbital osteocytes and to explore the
      mechanism of orbital implant in the prevention and treatment of orbital
      malformations. METHODS: It was an experimental research. Twenty-one age and
      weight-matched New Zealand rabbits were divided into three groups: enucleation
      group, enucleation with implant group and the control group. At one-month-old,
      the left eyes of the rabbits were enucleated in the enucleation group; an orbital
      implant was inserted after enucleation in the implant group. The left orbits of
      rabbits in the control group were served as the controls. At two-month-old, all
      rabbits were sacrificed, apoptosis of osteocytes of the zygomatic bones was
      observed by photomicroscopy, electron microscopy and TUNEL staining technology.
      The ratios of apoptosis osteocytes were calculated and analyzed in these three
      groups. RESULTS: Classical apoptosis of osteocytes was found with photomicroscopy
      and electron microscopy. The distribution of apoptosis of osteocytes was
      irregular in bone sections. The ratio of apoptosis cells in the enucleation group
      was significantly different from that in the other two groups (P<0.01). There was
      no significant difference in ratios of apoptosis cells between the implant group
      and the controls (P>0.05). CONCLUSIONS: Apoptosis of osteocytes participates in
      the normal development of bony orbit. The results of this study indicate that
      apoptosis of osteocytes plays a role in the development of orbital malformation
      after enucleation and orbital implant can prevent the orbital malformation after
      enucleation.

PMID- 19115633
TI  - [Effects of cisplatin on telomerase activity of human choroidal melanoma cells].
AB  - OBJECTIVE: To study the effects of CDDP (cis-dichlorodiamine platinum) on the
      telomerase of human choroidal melanoma cells and to investigate the toxic effects
      of CDDP on these cells. To study the relationship between these two effects and
      to explore the possibility of using CDDP in the chemotherapy of choroidal
      melanoma. METHODS: It was an experimental research. CDDP was added to the culture
      medium of primary cultured human choroidal melanoma cells at different
      concentrations (0.01, 0.1, 1, 10 and 100 mg/L, 72 h) and times (12, 24, 48, 72
      and 96 h, 10 mg/L) and the results were compared with that of the controls. Toxic
      effects of CDDP were evaluated by MTT test and the level of telomerase was
      measured by PCR-ELISA assay. The correlation between these two effects was
      analyzed. RESULTS: The telomerase activity was inhibited by CDDP time dependently
      and dose dependently. Cell viability was decreased when the concentration of CDDP
      attained 0.1 mg/L and acted for 24 hours. The cell toxicity of CDDP was
      correlated negatively (r = -0.900, P = 0.037) with the inhibition of telomerase.
      The cell death was lagged behind the decrease of telomerase. CONCLUSIONS: CDDP is
      an effective telomerase inhibitor which can decrease the telomerase activity of
      cultured human choroidal melanoma cells significantly. This effect is dose and
      time dependent. CDDP can also cause the death of cultured melanoma cells.

PMID- 19115634
TI  - [Enhanced near stereopsis after phacoemulsification and implantation of posterior
      chamber intraocular lens by prescribing addition properly].
AB  - OBJECTIVE: To improve near stereopsis in pseudophakic eyes after
      phacoemulsification and implantation of posterior chamber intraocular lens (IOL).
      METHODS: This prospective case-series study comprised 92 eyes of 46 patients aged
      50 to 70 years [mean age (61.33 +/- 5.54) years] who had phacoemulsification and
      implantation of posterior chamber IOL, including 24 unilateral pseudophakia
      (Group A) and 22 bilateral pseudophakia (Group B). The accommodative amplitude,
      relative accommodation, reading addition, near stereoacuity, etc. were measured.
      All data were analyzed with the SPSS11.0 for Windows. RESULTS: (1) The mean value
      of monocular accommodative amplitude in the group A and group B was (2.05 +/-
      1.12) and (2.35 +/- 1.30) D, respectively. (2) In the group A and group B, the
      binocular add was (2.08 +/- 0.37) and (2.13 +/- 0.46) D, respectively, and the
      monocular add was (2.20 +/- 0.42) and (2.01 +/- 0.39) D, respectively. There was
      a significant difference between the binocular add and the monocular add (t =
      2.33, 2.20, P<0.05) , and between left monocular add and right one (t =3.70,
      5.02, P<0.01) in each group. (3) The near stereopsis with monocular add was
      better than that with binocular add in each group, the difference was significant
      (X2 = 6.46, 7.02, P = 0.04, 0.03). CONCLUSION: Monocular add is beneficial to a
      pseudophakia with posterior chamber IOL implantation to improve near stereopsis.

PMID- 19115635
TI  - [The measured value of corneal hysteresis and resistance factor with their
      related factors analysis in normal eyes].
AB  - OBJECTIVE: The aim of this study was to investigate the corneal hysteresis (CH)
      and corneal resistance factor (CRF) in normal eyes and to determine their
      relationship between central corneal thickness (CCT), corneal curvature, sphere
      equivalence (SE) and intraocular pressure (IOP). METHODS: Cross-sectional study.
      This study included 205 normal eyes (205 patients). Ocular Response Analyzer
      (ORA, Reichert Ophthalmic Instruments, New York, USA) was used to measure CH and
      CRF. Multivariate regression analysis was applied to study their relationship
      between CCT, corneal curvature, SE, IOP (noncontact tonometer). RESULTS: The
      values of CH and CRF in 205 eyes presented normal distribution and concentrated
      on 8.1 to 11.0 mm Hg (1 mm Hg = 0.133 kPa). No statistical significant difference
      was found in both CH and CRF of different gender and ages (< 25 years or > or =
      25 years) (P > 0.05). 95% reference interval of CH and CRF in 205 eyes were 6.8
      to 13.0 mm Hg and 6.6 to 13.6 mm Hg. The correlation of CH and CRF with CCT,
      corneal curvature, SE and IOP were significant (P < 0.05). CONCLUSION: CH and CRF
      measure different biomechanical aspects of cornea, they may reflect the combined
      effect of CCT, corneal curvature, rigidity, hydration and IOP. These values of CH
      and CRF in normal eyes established foundation to further investigate their
      relationship with eye diseases.

PMID- 19115636
TI  - [Efficacy of protein-free calf blood extract for mechanical corneal epithelial
      defects in human eyes].
AB  - OBJECTIVE: To evaluate the clinical efficacy between protein-free calf blood
      extract eye drops and recombinant human epidermal growth factor (rhEGF) eye drops
      for mechanical corneal epithelial defects in human eyes. METHODS: A multi-center,
      randomized and double-blind study with a parallel, positive-control designation
      was carried out from April to November in 2005 at Department of Ophthalmology,
      Eye Ear Nose and Throat Hospital of Fudan University, Xinhua Hospital of Shanghai
      Jiaotong University, the First Hospital of Zhejiang University, the Second
      Hospital of Zhejiang University and Qingdao Municipal Hospital. 240 patients (240
      eyes) with confirmed diagnosis of corneal epithelial defects at that six
      hospitals were enrolled in this study and were randomly arranged into two groups
      in average. One group (120 eyes) were treated by 20% protein-free calf blood
      extract eye drops which was defined as the experimental group while the other
      (120 eyes) by 5000 IU/ml recombinant human epidermal growth factor (rhEGF) eye
      drops as the positive control group. The drug was delivered in both groups 4
      times per day, one drop each time in the 14 days duration. The symptoms and signs
      were scored and the safety was evaluated on the pre-delivery day, the third post
      delivery day (day 3), day 7 and day 14. The variants in the study were tested for
      the different efficacy and safety between the two drugs using non-inferiority
      test, paired t-test, Wilcoxon signed-rank test, chi-square test, continuity
      correction chi-square test, Fisher's exact probabilities, analysis of variance,
      Cochran-Mantel-Haenszel chi-square test and so on. The criterion for statistical
      significance was P < 0.05. RESULTS: There was no significant difference in
      efficacy between the protein-free calf blood extract group and the recombinant
      human epidermal growth factor group (day 3: X2 = 1.5677, P = 0.4566, day 7: X2 =
      1.7152, P = 0.4242, day 14: X2 = 3.0814, P = 0.2142). The total scores of
      symptoms and signs in experimental group had a obvious descending (6.009 +/-
      3.030) compared with the positive control group with a descending of (5.177 +/-
      2.582), which reached the significant level (t = 2.2367, P = 0.0263). Ocular
      local stimulates and general side effect were not observed within the treatment
      course. There was no significant difference between the two groups in the
      comparison of pre- and post-therapy visual acuity. The difference was not
      significant when comparing the uncomfortable feelings, including eye burning and
      eye itching (eye burning: day 3: X2 = 0.4394, P = 0.932, day 7: X2 = 1.4710, P =
      0.479,day 14: X2 = 2.1875, P= 0.335, and eye itching: day 3: X2 = 2.1045, P =
      0.349, day 7: X2 = 2.0192, P = 0.364, day 14: X2= 0.6863, P = 0.407). And the
      positive control group gave priority to the experimental group in comfortability.
      A better comfortableness was reported in the protein-free calf blood extract
      group on the third day post-delivery (X2 = 6.626, P = 0.0100). However, no
      obvious difference was examined on day 7 and day 14 post-delivery. CONCLUSION:
      Protein-free calf blood extract eye drops has confirmed efficacy, good safety,
      quick effect and better comfortableness.

PMID- 19115637
TI  - [Deep lamellar endothelial keratoplasty for bullous keratopathy].
AB  - OBJECTIVE: To investigate the efficacy, postoperative complications and
      management of deep lamellar endothelial keratoplasty (DLEK) in complex cases of
      severe bullous keratopathy. METHODS: In the nonrandomized retrospective
      consecutive case series, fifteen cases (15 eyes) of severe and complex bullous
      keratopathy at Zhongshan Ophthalmic Center underwent DLEK in combination with
      other intraocular surgeries between October 2005 and March 2006. DLEK was
      combined with vitrectomy and ciliary sulcus sutured intraocular lens implantation
      in two patients, with vitrectomy and intraocular lens extraction in two patients
      and with vitrectomy and intraocular lens exchange in one patient Four patients
      with aphakic eyes underwent subsequent ciliary sulcus sutured intraocular lens
      implantation within 4 to 6 months after the DLEK donor tissue had been placed.
      The best spectacle corrected visual acuity (BSCVA), corneal astigmatism,
      curvature and endothelial cell density (ECD) were examined preoperatively and
      postoperatively. The graft-host interface was photographed by anterior segment
      optic coherent tomography (OCT). Repeated Measures Anova was applied for
      management of the data. RESULTS: On postoperative day 1, 13 grafts were well
      attached to the host except for one dislocation (re-located immediately and well
      attached). Fluid leakage between the graft-host interface occurred in one eye
      (absorbed on day 5). All the grafts remained clear during the follow-up. Five
      cases (33.3%) showed narrow gaps between the borders of graft and host. Bullous
      epithelial lesion reoccurred above the gap in two cases (13.3%), and disappeared
      during follow-up. BSCVA in 4 eyes (26.7%) was 0.4, in 3 eyes (20.0%) was 0.3, in
      4 eyes (26.7%) was 0.2, and in 1 eye (6.7%) was 0.1 after DLEK. At 6, 9 and 12
      months, the average corneal astigmatism were (2.80 +/- 0.70) D, (2.60 +/- 0.70) D
      and (2.20 +/- 0.60) D (F = 5.591, P = 0.090), average corneal curvature were
      (43.60 +/- 1.90) D, (44.10 +/- 1.30)D and (44.10 +/- 1.00) D (F =1.515, P =
      0.237). The average central corneal thickness were (666.1 +/- 70.6) microm,
      (544.5 +/- 30.9) microm, (538.2 +/- 34.7) microm and (532.4 +/- 41.6) microm (F =
      32.692, P = 0.000) at preoperatively, 6, 9 and 12 months postoperatively,
      respectively. The mean ECD was (1915.7 +/- 90.8) cells/mm2 postoperatively.
      CONCLUSIONS: DLEK surgery is an effective and safe procedure in severe and
      complex cases of bullous keratopathy,but it has to be successfully combined with
      other anterior segment surgeries. DLEK graft without sutures can tolerate
      subsequent other anterior segment surgeries at 4 to 6 months after placement of
      the donor tissue.

PMID- 19115638
TI  - [Expression of vascular endothelial growth factor and pigment epithelium derived
      factor in mouse oxygen-induced retinopathy and its significance].
AB  - OBJECTIVE: To investigate the expression and significance of vascular endothelial
      growth factor (VEGF) and pigment epithelium derived factor (PEDF) in oxygen
      induced mouse retinopathy. METHODS: This experiment was a control experiment
      study. Newborn C57BL-6 mice were exposed to hyperoxia, and then returned to
      normoxia to induce retinal neovascularization. Mice were sacrificed at postnatal
      days 12, 14 and 17 and the retina were processed for RT-PCR, Western Blot and
      fluorescein angiography. Analysis of variance and Dunnett's t3 was used to
      compare the mRNA and protein level of VEGF and PEDF between experiment and
      control groups. Statistical difference was considered significant at a P value
      less than 0.05. RESULTS: At any of the time points tested, there was significant
      difference at VEGF protein level (A value) between the experiment (0.47 +/- 0.12,
      2.15 +/- 0. 46, 5.49 +/- 0.97) and control (l.81 +/- 0.50, 0.90 +/- 0.05, 0.88 +/
      0.91) groups (P = 0.009, 0.010, 0.000, respectively); the same situation
      occurred at PEDF protein level (P = 0.002, 0.046, 0.000, respectively). At
      postnatal day 12, 14 and 17, a significant difference at VEGF protein level was
      observed among the different experiment groups (P = 0.002, 0.001, 0.000,
      respectively); the same situation occurred at PEDF protein level (P = 0.009,
      0.010, 0.000, respectively). There was significant difference at VEGF mRNA level
      between the experiment and control groups (P = 0.001, 0.000, 0.001); at postnatal
      day 12 and 14, the same situation occurred at PEDF protein level (P = 0.001,
      0.000, respectively), but there was no significant difference at postnatal day 17
      (P = 0.612). At postnatal day 12, 14 and 17, a significant difference at VEGF
      mRNA level was observed among different experiment groups (P = 0.000, 0.001,
      0.000, respectively); the same situation occurred at PEDF mRNA level (P = 0.000,
      0.001, 0.000, respectively). The time course of the decrease of PEDF was
      consistent with the increase of VEGF expression. VEGF/PEDF ratio change was
      correlated with the development and progression of retinal neovascularization.
      The time course of PEDF mRNA down-regulation was consistent with the VEGF mRNA up
      regulation, similar with the changes of the protein. The change of VEGF and PEDF
      mRNA was prior to that of the protein. CONCLUSIONS: One of the mechanisms for
      development of retinal neovascularization is the changes of VEGF?PEDF level in
      the retina.

PMID- 19115639
TI  - [RNA interference targeting aquaporin-1 on inhibition of human vascular
      endothelial cell migration in vitro].
AB  - OBJECTIVE: To investigate inhibition of human vascular endothelial cell migration
      in vitro by RNA interference targeting AQP-1, and the mechanism of corneal
      neovascularization. METHODS: Experiment research. Human umbilical vein
      endothelial cell (HUVEC) was cultured, AQP-1 specific siRNA was designed and
      synthesized. siRNA was transfected into the HUVEC by Lipofectamine 2000. The mRNA
      of AQP-1 was assessed by reverse transcription-polymerase chain reaction (RT
      PCR). Transwell migration assay and wound healing assay were used to detect the
      migration capability of HUVEC. The group comparison of AQP-1 mRNA expression was
      used one-way ANOVA test The result of transwell migration assay and wound healing
      assay was analysed with Independent-Sample T test. RESULTS: The expression of AQP
      1 mRNA was significantly (P < or = 0.05) suppressed after transfection. 24 h, 48
      h and 72 h, after transfection, the expression of AQP-1 mRNA was 11.3%, 17.4% and
      29.7% respectively compared to normal control (P = 0.004, 0.007, 0.002).
      Transwell migration assay and wound healing assay showed that the migration
      capability of HUVEC was decreased obviously (t = 10.813, P = 0.016 and t =
      22.431, P = 0.027). CONCLUSIONS: AQP-1 specific siRNA is effective in suppressing
      the AQP-1 expression and inhibiting the migration of the cultured HUVEC. Reducing
      the expression of AQP-1 can inhibit the corneal neovascularization.

PMID- 19115640
TI  - [Progress in studies on effects of extracellular matrix in occurrence of
      proliferative vitreoretinopathy].
AB  - It has been found that various extracellular matrix (ECM) probably play an
      important role in the occurrence of proliferative vitreoretinopathy (PVR),
      including structural proteins, adhesive proteins, anti-adhesive proteins, matrix
      metalloproteinase (MMP), and tissue inhibitor of MMP (TIMP) Structural proteins,
      including collagen and elastic fiber family, are the major non-cellular
      components of PVR membrane, and could promote contraction of membrane. Adhesive
      proteins, including fibronectin, vitronectin, laminin, could promote adhesion
      between cells and ECM in PVR, they promote the attachment, migration and
      differentiation of retinal pigment epithelium (RPE). Anti-adhesive proteins,
      including thrombospondin-1, osteonectin, tenascin, could promote RPE migration
      and tissue remodeling of PVR, etc. MMPs and TIMPs could degrade some components
      of ECM, enhance permeability of blood vessel and promote neovascularization in
      PVR.

PMID- 19115641
TI  - The pulse oximeter.

PMID- 19115642
TI  - Should we take a different angle in managing pregnant women at delivery?
      Attempting to avoid the 'supine hypotensive syndrome'.

PMID- 19115643
TI  - A case of redundant publication: statement from the chief editor.

PMID- 19115644
TI  - Comparison between sevoflurane/remifentanil and propofol/remifentanil anaesthesia
      in providing conditions for somatosensory evoked potential monitoring during
      scoliosis corrective surgery.
AB  - Somatosensory evoked potential (SSEP) monitoring is an important tool in spinal
      corrective surgery. Anaesthesia has a significant influence on SSEP monitoring
      and a technique which has the least and shortest suppressant effect on SSEP while
      facilitating a fast recovery from anaesthesia is ideal. We compared the effect of
      sevoflurane/ remifentanil and propofol/remifentanil anaesthesia on SSEPs during
      scoliosis corrective surgery and assessed patients' clinical recovery profiles.
      Twenty patients with idiopathic scoliosis receiving surgical correction with
      intraoperative SSEP monitoring were prospectively randomised to receive
      sevoflurane/remifentanil anaesthesia or propofol/remifentanil anaesthesia. During
      surgery, changes in anaesthesia dose and physiological variables were recorded,
      while SSEP was continuously monitored. A simulated 'wake-up' test was performed
      postoperatively to assess speed and quality of recovery from anaesthesia. The
      effects of propofol and sevoflurane resulted in SSEP amplitude variability
      between 18.0% +/- 3.5% to 28.7% +/- 5.9% and SSEP latency variability within 1.3%
      +/- 0.4% to 2.6% +/- 1.2%. Patients receiving sevoflurane had faster suppression
      and faster recovery of SSEP amplitude compared to propofol (P < 0.05), although
      propofol anaesthesia showed less within-patient variability in Cz amplitude and
      latency (P < 0.05). On cessation of anaesthesia, time to eye-opening (5.2 vs.
      16.5 minutes) and toe movement (5.4 vs. 17.4 minutes) was shorter following
      sevoflurane (all P < 0.05). These findings indicate that propofol produces a
      better SSEP signal than sevoflurane. However adjustments in sevoflurane
      concentration result in faster changes in the SSEP signal than propofol.
      Assessment of neurological function was facilitated more rapidly after
      sevoflurane anaesthesia.

PMID- 19115645
TI  - Continuous interscalene analgesia for rotator cuff repair: a retrospective
      comparison of effectiveness and cost in 205 patients from a multi-provider
      private practice setting.
AB  - Several barriers exist to the routine use of continuous interscalene block (CISB)
      for postoperative analgesia following rotator cuff repair There is a perception
      that the technique is feasible only for single operators exposed to a high volume
      case load. The aim of this retrospective review was to compare the three commonly
      employed analgesic techniques following rotator cuff repair in a multi-provider
      setting. The techniques studied were CISB, combined single injection interscalene
      block with postoperative intermittent intra-articular local anaesthetic
      infiltration (SSISB/IA) and intermittent intra-articular only local anaesthetic
      infiltration (IA). The clinical records of 205 consecutive patients having open
      rotator cuff repair over an 18-month period in two private care facilities were
      reviewed. The primary outcome endpoint was total opioid/tramadol consumption
      during the period of an overnight hospital stay. The median total opioid and
      tramadol consumption (in intravenous mg equivalents of morphine) from admission
      to the post anaesthesia care unit until discharge from hospital was 5 mg in the
      CISB group and 10 mg for the SSISB/IA and IA groups (P < 0.0001). The proportion
      of subjects requiring more than one antiemetic for the same period was 1.9% in
      the CISB group, 16.4% for the SSISB/IA group and 36.1% for the IA group (P <
      0.0001). Costs related to the analgesic technique were similar in each group.
      CISB following rotator cuff repair in a multi-provider setting was associated
      with reduced total opioid/tramadol and antiemetic consumption, and occurred
      without a significant increase in the monetary cost.

PMID- 19115646
TI  - Effect of recruitment and body positioning on lung volume and oxygenation in
      acute lung injury model.
AB  - The mechanism of oxygenation improvement after recruitment manoeuvres or prone
      positioning in acute lung injury or acute respiratory distress syndrome is still
      unclear. We tried to determine the mechanism responsible for the effects of
      recruitment manoeuvres or prone positioning on lung aeration using a whole lung
      computed tomography scan in an oleic acid induced acute lung injury canine model.
      Twelve adult mongrel dogs were allocated into either the supine group (n=6) or
      the prone group (n=6). After the establishment of acute lung injury, three
      recruitment manoeuvres were performed at one-hour intervals. Haemodynamic and
      ventilatory variables, arterial blood gas analyses and CT scans of the whole lung
      were obtained 90 minutes after oleic acid injection and five minutes before and
      after each recruitment manoeuvre. Recruitment manoeuvres in the supine position
      improved oxygenation (P=0.025) that correlated with increase of the poorly- and
      well-aerated dorsal (dependent) lung volume (r=0.436, P=0.016). Prone positioning
      increased oxygenation (P=0.004) that also correlated with increase of the poorly-
      and well-aerated dorsal (nondependent) lung volume (r=0.787, P<0.001). However,
      the recruitment manoeuvre in the prone position had no effect on oxygenation
      despite an increase in ventral (dependent) lung volume. The increase in PaO2
      after recruitment manoeuvres in the supine position or after prone positioning is
      related to the increase of the poorly- and well-aerated dorsal lung.

PMID- 19115647
TI  - Effect of open-chest surgery in the lateral position on blood propofol
      concentration during target-controlled infusion of propofol.
AB  - Our research hypothesis was that single lung ventilation during thoracic surgery
      in the lateral position increases the blood concentration of propofol during
      target-controlled infusion. Thirty adult patients in two tertiary referral
      hospitals undergoing open-chest surgery were studied. Anaesthesia was induced and
      maintained with propofol using a Diprifusor (Graseby 3500) computer-controlled
      pump set to deliver a blood concentration of 4 tg.ml(-1). Blood samples were
      taken with the patient positioned in (1) the supine position 20 minutes after
      induction (supine); (2) the lateral position just prior to one-lung ventilation
      (lateral); (3) the lateral position five minutes after commencing one-lung
      ventilation (OLV5) and (4) the lateral position 20 minutes after commencing one
      lung ventilation (OLV20). Propofol concentrations were determined by high
      performance liquid chromatography. The target-controlled infusion target level
      was maintained at 4 microg.ml(-1) during the study period for all cases. The mean
      (SD) propofol blood concentration (microg.ml(-1)) at each stage was 5.5 (1.5)
      supine, 5.3 (1.1) lateral, 5.3 (1.2) OLV5 and 5.1 (1.2) OLV20. Repeated measures
      ANOVA showed an F value 1.9, lambda 5.5 and P value 0.15. Post hoc analysis did
      not identify a significant difference between the sample times. During target
      controlled infusion of propofol, mean blood propofol concentrations did not
      change significantly from those obtained with the patient supine after up to 50
      minutes in the lateral position during thoracic surgery, or 20 minutes after
      commencing one-lung ventilation.

PMID- 19115648
TI  - In vitro effects of propofol on gravid human myometrium.
AB  - The aim of this study was to evaluate the direct effect of propofol (di-isopropyl
      phenol) on the contractile properties of gravid human uterine muscle. Six
      specimens of uterine muscle were obtained from term parturients undergoing
      elective lower segment caesarean section. Small strips (1 x 2 x 12 mm) of muscle
      were prepared and suspended in an organ bath containing oxygenated Kreb's
      solution at 36.5 degrees C. Following preparation, spontaneous regular
      contractions developed at a rate of one contraction every six to 10 minutes.
      Force of contraction was recorded continuously using an isometric tension
      transducer Following baseline measurements, propofol was introduced into the bath
      at concentrations corresponding to 2 microg/ml, 5 mcirog/ml and 8 mirog/ml. The
      specimens were also exposed to intralipid in concentrations equivalent to that
      found in the 8 microg/ml solution of propofol to determine whether this additive
      influenced uterine contractility. Contractility (defined as area under the
      tension/time curve) was decreased to 89 +/- 6.5% of control at 2 microg/ml, 53 +/
      4.3% at 5 microg/ml and 45 +/- 4.1% at 8 microg/ml. This decrease in
      contractility was statistically significant at concentrations >2 microg/ml.
      Intralipid did not significantly affect uterine contractility. The results of
      this study show that propofol decreases isolated human uterine muscle
      contractility in a dose-dependent manner

PMID- 19115649
TI  - Performance of BIS in children using the paediatric BIS Quattro sensor.
AB  - The Bispectral Index (BIS) is one of the most frequently used
      electroencephalogram-derived depth of anaesthesia monitors. Previous studies in
      children have suggested BIS performs well in older children, however these
      studies have used earlier versions of the BIS device. The aim of this study was
      to compare the performance of BIS over different age groups using the BIS
      paediatric Quattro sensor (Aspect Medical Systems, Norwood, MA, U.S.A.). One
      hundred and eighty children between one and 13 years were enrolled. At a
      predetermined time during emergence from anaesthesia, wakefulness was assessed
      and BIS recorded. For analysis, children were divided into four groups (one to
      three, three to six, six to nine and nine to 13 years) and for each age group a
      receiver operating characteristic curve was generated. Areas under the curve were
      compared across age groups. Good quality BIS data was available in 161 children.
      The areas under the curves for each age group were: one to three years 0.80,
      three to six years 0.88, six to nine years 0.85 and nine to 13 years 0.95.
      Although the area was least in the youngest age group and greatest in the oldest
      age group, there was no evidence for a difference when tested with ANOVA
      (P=0.26). When combining all age groups taking a BIS value of 50 or greater
      provided 100% sensitivity to detect wakefulness. This study found no evidence for
      any substantial difference in performance between ages one and 13 years. If BIS
      is used in children to detect wakefulness occurring with lightening of
      anaesthesia, then this study suggests that if the BIS is maintained below 50 then
      wakefulness is unlikely to have occurred.

PMID- 19115650
TI  - Postoperative patient-controlled thoracic epidural analgesia: importance of dose
      compared to volume or concentration.
AB  - This randomised and blinded study evaluated the quality of analgesia and the
      incidence of side-effects of two concentrations of levobupivacaine (0.15% and
      0.5%) given as an equal mg-bolus-dose (5 mg) via patient-controlled epidural
      analgesia after lower abdominal surgery. The patients were randomly assigned into
      two groups to receive either 0.15% levobupivacaine as a 3.3 ml bolus on demand,
      with a lockout interval of 30 minutes (n=30), or 0.5% levobupivacaine as a 1 ml
      bolus on demand, with a similar lockout interval (n=30). For both groups we
      combined the bolus on demand with a background infusion of 5 mg/hour
      levobupivacaine, i.e. 3.3 ml/hour 0.15% or 1 ml/hour 0.5% of levobupivacaine. The
      epidural catheters were inserted in a lower thoracic intervertebral space before
      induction of general anaesthesia. The following variables were registered in the
      48 hours after surgery: upper and lower sensory block, pain scores at rest and
      after coughing, rescue morphine consumption, motor blockade, haemodynamic
      (arterial blood pressure and heart rate), nausea and vomiting, and patient
      satisfaction ratings. The two groups had similar sensory block, quality of
      analgesia, rescue morphine consumption requirement, motor blockade and side
      effects, and both had a high satisfaction rate. These findings indicate that
      administering the same dose of levobupivacaine in either a low or high
      concentration via the patient-controlled epidural analgesia mode, combined with a
      background infusion, provides an equal quality of analgesia for low thoracic
      level epidurals with no difference in the incidence of side-effects.

PMID- 19115651
TI  - Acid-base effects of a bicarbonate-balanced priming fluid during cardiopulmonary
      bypass: comparison with Plasma-Lyte 148. A randomised single-blinded study.
AB  - Fluid-induced metabolic acidosis can be harmful and can complicate
      cardiopulmonary bypass. In an attempt to prevent this disturbance, we designed a
      bicarbonate-based crystalloid circuit prime balanced on physico-chemical
      principles with a strong ion difference of 24 mEq/l and compared its acid-base
      effects with those of Plasma-Lyte 148, a multiple electrolyte replacement
      solution containing acetate plus gluconate totalling 50 mEq/l. Twenty patients
      with normal acid-base status undergoing elective cardiac surgery were randomised
      1:1 to a 2 litre prime of either bicarbonate-balanced fluid or Plasma-Lyte 148.
      With the trial fluid, metabolic acid-base status was normal following bypass
      initiation (standard base excess 0.1 (1.3) mEq/l, mean, SD), whereas Plasma-Lyte
      148 produced a slight metabolic acidosis (standard base excess -2.2 (2.1) mEq/l).
      Estimated group difference after baseline adjustment was 3.6 mEq/l (95%
      confidence interval 2.1 to 5.1 mEq/l, P=0.0001). By late bypass, mean standard
      base excess in both groups was normal (0.8 (2.2) mEq/l vs. -0.8 (1.3) mEq/l,
      P=0.5). Strong ion gap values were unaltered with the trial fluid, but with
      Plasma-Lyte 148 increased significantly on bypass initiation (15.2 (2.5) mEq/l
      vs. 2.5 (1.5) mEq/l, P < 0.0001), remaining elevated in late bypass (8.4 (3.4)
      mEq/l vs. 5.8 (2.4) mEq/l, P < 0.05). We conclude that a bicarbonate-based
      crystalloid with a strong ion difference of 24 mEq/l is balanced for
      cardiopulmonary bypass in patients with normal acid-base status, whereas Plasma
      Lyte 148 triggers a surge of unmeasured anions, persisting throughout bypass.
      These are likely to be gluconate and/or acetate. Whether surges of exogenous
      anions during bypass can be harmful requires further study.

PMID- 19115652
TI  - Effects of pregnancy on the solubility of halogenated volatile anaesthetics in
      rat blood and tissues.
AB  - This study was designed to evaluate the effects of pregnancy on the solubility of
      halogenated volatile anaesthetics in rat blood and tissues. Tissue samples from
      10 pregnant and 10 non-pregnant adult female Sprague Dawley rats, including the
      heart, liver, kidney and brain, were obtained and made into respective
      homogenates. Blood/gas and tissue/gas partition coefficients for halothane,
      sevoflurane and isoflurane were determined by the method of two-stage headspace
      equilibration by gas chromatography with each of the homogenates. Values were
      analysed by t-test or one-way analysis of variance. The solubility within blood
      and brain for halothane in the pregnant group (2.90 +/- 0.44, 5.55 +/- 0.73) was
      significantly lower than that of the non-pregnant group (3.42 +/- 023, 6.33 +/-
      0.64; P < 0.05). However, there were no significant differences between the two
      groups for liver, kidney or heart solubility. For sevoflurane and isoflurane,
      there were no significant differences in solubility between the two groups. In
      conclusion, pregnancy decreased the solubility of halothane within the blood and
      brain, whereas the solubility of halothane in other tissues including the liver,
      kidney and heart showed no significant alteration. Pregnancy did not affect the
      solubility ofsevoflurane or isoflurane within blood or the other tissues studied.

PMID- 19115653
TI  - Lumbar wedge versus pelvic wedge in preventing hypotension following combined
      spinal epidural anaesthesia for caesarean delivery.
AB  - Aortocaval compression is a major cause of maternal hypotension. A randomised
      controlled clinical trial was designed to compare two wedged supine positions for
      prevention of hypotension following combined spinal epidural anaesthesia for
      caesarean delivery. Sixty parturients undergoing elective caesarean delivery were
      randomly assigned to two different wedged supine positions. After the completion
      of subarachnoid injection, parturients were placed with either a wedge under the
      right pelvis (group P pelvic wedge) or under the right lumbar region (group L,
      lumbar wedge). Systolic blood pressure and heart rate were recorded every minute
      for 20 minutes from the subarachnoid injection. Hypotension, defined as systolic
      blood pressure <100 mmHg or 80% of the baseline, was treated with intravenous
      ephedrine 5 mg. The incidence of hypotension, ephedrine use and neonatal Apgar
      scores and umbilical arterial pH were recorded. The incidence of hypotension was
      significantly higher in group P than that in group L (23/30 [77%] vs. 14/30
      [47%], P=0.016). Systolic blood pressure decreased significantly in both groups
      at seven, eight and nine minutes (P < 0.001); moreover it was lower at seven,
      eight and nine minutes in group P than in group L (P < 0.01). Heart rate did not
      change significantly in either group. There were no significant differences
      between the two groups for Apgar score and umbilical arterial pH. A lumbar wedge
      is more effective than a pelvic wedge in preventing hypotension following
      combined spinal epidural anaesthesia for caesarean delivery, although it does not
      eliminate hypotension.

PMID- 19115654
TI  - Evaluation of the efficacy of magnesium sulphate as an adjuvant to lignocaine for
      intravenous regional anaesthesia for upper limb surgery.
AB  - Several additives have been combined with local anaesthetics for intravenous
      regional anaesthesia to improve block quality, analgesia and to decrease
      tourniquet pain. Magnesium sulphate is one potential additive. This prospective,
      randomised, double-blinded study was conducted in 30 ASA physical status I or II
      patients undergoing upper limb surgery under tourniquet. In group L, patients
      received intravenous regional anaesthesia with lignocaine alone (9 ml of 2%
      lignocaine diluted with normal saline to total volume of 36 ml). Patients in
      group M received intravenous regional anaesthesia with lignocaine plus magnesium
      sulphate (6 ml of 25% magnesium sulphate plus 9 ml of 2% lignocaine diluted with
      normal saline to total volume of 36 ml). Assessment was by observing the response
      to injection of drug; sensory and motor block and tourniquet pain. The mean time
      of onset of sensory block was 12.40 and 3.47 minutes in groups L and M
      respectively (P < 0.001). The average times of onset of motor block in groups L
      and M were 17 and six minutes respectively (P < 0.001). Of the patients in group
      M, 66.7% reported moderate to severe pain while the drug was being injected,
      compared to 20% in group L (P=0.011). There was a statistically significant
      difference in visual analogue scale for tourniquet pain at 10 and 30 minutes
      after tourniquet inflation (lower in group M). These findings indicate that
      magnesium sulphate added as an adjuvant to lignocaine hastens the onset of
      sensory and motor block and decreases tourniquet pain. However there is increased
      incidence of transient pain on injection if magnesium sulphate is added.

PMID- 19115655
TI  - Comparison of intensive care outcome prediction models based on admission scores
      with those based on 24-hour data.
AB  - We compared the performance of six outcome prediction models--three based on 24
      hour data and three based on admission-only data--in a metropolitan university
      affiliated teaching hospital with a 10-bed intensive care unit. The Acute
      Physiology and Chronic Health Evaluation models, version II (APACHE II) and
      version III-J, and the Simplified Acute Physiology Score version II (SAPS II) are
      based on 24-hour data and were compared with the Mortality Prediction Model
      version II and the SAPS version III using international and Australian
      coefficients (SAPS IIIA). Data were collected prospectively according to the
      standard methodologies for each model. Calibration and discrimination for each
      model were assessed by the standardised mortality ratio, area under the receiver
      operating characteristic plot and Hosmer-Lemeshow contingency tables and chi
      squared statistics (C10 and H10). Predetermined criteria were area under the
      receiver operating characteristic plot > 0.8, standardised mortality ratio 95%
      confidence interval includes 1.0, and C10 and H10 P values >0.05. Between October
      1, 2005 and December 31, 2007, 1843 consecutive admissions were screened and
      after the standard exclusions, 1741 were included in the analysis. The SAPS II
      and SAPS IIIA models fulfilled and the APACHE II model failed all criteria. The
      other models satisfied the discrimination criterion but significantly over
      predicted mortality risk and require recalibration. Outcome prediction models
      based on admission-only data compared favourably to those based on 24-hour data.

PMID- 19115656
TI  - Efficacy of low dose levobupivacaine (0.1%) for axillary plexus block using
      multiple nerve stimulation.
AB  - The purpose of this study was to investigate if low doses of levobupivacaine
      (0.1%) produce complete sensory blockade in preoperative axillary brachial plexus
      block and to compare the effect of different doses of levobupivacaine on sensory
      and motor blockade. A total of 110 patients scheduled for elective forearm or
      hand surgery were randomly allocated to receive 36 ml or 72 ml of levobupivacaine
      0.1% or 36 ml of levobupivacaine 0.25%. In each group, volumes were equally
      distributed in the four nerve territories. In all patients, the sensory and motor
      block was assessed at five, 10, 20 and 30 minutes after the placement of axillary
      block. Complete sensory block was obtained in 94.4% of patients receiving 36 ml
      of levobupivacaine 0.1%, 92.1% of those receiving 72 ml of levobupivacaine 0.1%,
      and 97.1% of those receiving 36 ml of levobupivacaine 0.25%. There was no
      significant difference either in the onset of the sensory and motor block or
      duration of the sensory and motor block. This study demonstrates that 36 ml of
      levobupivacaine 0.1% (36 mg) is as effective as higher doses and volumes in
      axillary brachial plexus blockade.

PMID- 19115657
TI  - Comparison of stress in anaesthetic trainees between Hong Kong and Victoria,
      Australia.
AB  - A postal survey was sent to anaesthetic trainees in Hong Kong and Victoria,
      Australia to compare work-related stress levels. Demographic data were collected.
      Anaesthetist-specific stressors, Maslach Burnout Inventory and Global Job
      Satisfaction scores were used for psychological testing. The response rates from
      Hong Kong and Melbourne were 64 of 133 (48.1%) and 108 of 196 (55.1%),
      respectively. Victorian respondents were older with greater family commitments,
      but more advanced in fulfilling training requirements. Hong Kong respondents,
      being faced with both the challenge of dual College requirements, exhibited
      consistently higher indices of stress (P < 0.001) and less job satisfaction (P <
      0.001). Common occupational stressors related to dealing with critically ill
      patients and medicolegal concerns. Higher stress scores observed in Hong Kong
      trainees related to service provision and a perceived lack of resources. Despite
      the complex nature of stress, its antecedents and manifestations, an inverse
      relationship between emotional exhaustion and job satisfaction was evident in
      correlation analysis (P < 0.001). This survey suggests that stress was present in
      some trainees in both areas. Hong Kong trainees may benefit from local
      development to address mental wellbeing as being important to fulfil this highly
      competitive training program.

PMID- 19115658
TI  - Tumour metastasis at the site of a previous epidural catheter.
AB  - Epidural catheters can cause a number of rare, serious complications. The
      following case report describes a patient who received continuous epidural
      analgesia following radical cystectomy for bladder cancer Fifty-three days after
      the cystectomy, the patient underwent emergency surgery for a metastasis at the
      vertebral level where the epidural catheter had been inserted. A metastasis at
      the site of an epidural catheter which may be a direct complication of epidural
      analgesia, is a previously unreported event. Local, anatomical and pathological
      factors which may have led to the patient developing a metastasis at the epidural
      site are discussed.

PMID- 19115659
TI  - Guillain-Barre syndrome with absent brainstem reflexes--a report of two cases.
AB  - Guillain-Barre syndrome, known for its diverse, atypical and heterogeneous range
      of presentations, can rarely present in an apparent comatose state with absent
      brainstem reflexes. Two patients presented in an unresponsive state with flaccid
      quadriplegia, total areflexia with no response to cephalic or peripheral painful
      stimuli. Pupils were mid-dilated with absent direct and consensual light reflex.
      All cranial nerve reflexes were absent. Preliminary laboratory investigations and
      complementary tests were normal. Cerebrospinal fluid evaluation showed
      albumincytological dissociation. Brain magnetic resonance imaging and
      electroencephalogram were normal. Both were diagnosed as fulminant Guillain-Barre
      syndrome. Despite an absence of brainstem reflexes neither patient fulfilled
      diagnostic criteria for brain death.

PMID- 19115660
TI  - Palatopharyngeal wall perforation during Glidescope intubation.
AB  - We report a case of palatopharyngeal wall perforation during intubation with a
      GlideScope laryngoscope. The likely mechanism was advancing and rotating the
      endotracheal tube against a taut palatopharyngeal fold. This was missed during
      the initial laryngoscopy, because there is a potential blind-spot in the
      oropharynx when attention is focused on the GlideScope" monitor Fortunately,
      there were no sequelae other than minor bleeding and a mild sore throat and no
      surgical intervention was necessary. The use of unnecessary force during the
      endotracheal tube insertion, the use of too large a laryngoscope blade and the
      use of a rigid stylet could possibly also have been contributory factors to this
      complication.

PMID- 19115661
TI  - Postpartum septic sacroiliitis coincident with labour epidural analgesia.
AB  - A 22-year-old woman presented to hospital 10 days after emergency caesarean
      section with severe back pain, fever tachycardia and a raised C-reactive protein.
      She had received labour epidural analgesia and was investigated for an epidural
      abscess. After repeat magnetic resonance imaging she was ultimately diagnosed
      with septic sacroiliitis. Although an uncommon cause of back pain, pregnancy
      associated sacroiliitis should be considered in the differential diagnosis of
      post-epidural back pain, as the presentation and symptoms of an epidural
      infection and sacroiliitis are similar. We recommend imaging to include the
      sacroiliac joints when considering the diagnosis of an epidural collection.

PMID- 19115662
TI  - Tracheal tube position during percutaneous tracheostomy.

PMID- 19115663
TI  - Precautions with a modified stimulating Touhy needle.

PMID- 19115664
TI  - Recycling plastics from the operating suite.

PMID- 19115665
TI  - Comparison of lateral and standard techniques of laryngeal mask airway insertion
      in adults.

PMID- 19115666
TI  - Reduced midazolam clearance must be considered in prolonged coma.

PMID- 19115667
TI  - Intra-aortic balloon pump microperforation resulting in balloon entrapment.

PMID- 19115668
TI  - Recurarisation in a surgical ward.

PMID- 19115669
TI  - Attitudes of anaesthetic, theatre and intensive care unit staff to labelling of
      ampoules.

PMID- 19115670
TI  - The Glasgow Coma Scale--a brief review. Past, present, future.
AB  - The Glasgow Coma Scale (GCS) was introduced in 1974 aiming at standardizing
      assessment of level of consciousness in head injured patients. It has been used
      mainly in evaluating prognosis, comparing different groups of patients and
      monitoring the neurological status. However its use expanded beyond the original
      intention of the scale and certain limitations were identified. The skewness
      toward the motor subscore, the experience of the raters, the process of
      intubation, the time and setting of rating among others are to be taken into
      account. In this review a thorough presentation of this scale's history,
      principles of scoring and associated common pitfalls, major applications and
      drawbacks is attempted. Moreover, future trends and implications are considered.
      The key concept in all articles reviewed is that even though GCS is not a perfect
      tool and other coma scales have been proposed, it seems destined to be
      incorporated in clinical decisions regarding coma for many years to come.
      Nonetheless, deep knowledge of its proper applications on one hand and limitation
      of its misuse on the other is essential to benefit both health care professionals
      and their patients.

PMID- 19115671
TI  - The effect of male circumcision on pudendal evoked potentials and sexual
      satisfaction.
AB  - Circumcision is generally considered a simple, rapid operation with medical
      benefits which accrue throughout life. The influence of circumcision on sexual
      satisfaction has always been argued. In this study, the assessment of the
      pudendal evoked potentials (PEP) in adults before and at least 12 weeks after
      circumcision was done. Healthy males aged between 18-27 years, who were willing
      to undergo circumcision were included in the study. Before and after
      circumcision, sexual performance was evaluated with the Brief Male Sexual
      Function Inventory (BMSFI), consisting of sexual drive, erection, ejaculation,
      problem assessment, and overall satisfaction sections. Forty-three adult males
      were enrolled in the study. Mean PEP latency was 41.97 +/- 0.25 (39.90-44.50) ms
      and 44.73 +/- 0.33 (40.90-47.60) ms before and after circumcision, respectively.
      Mean difference between pre- and postoperative PEP values was 2.76 ms which was
      statistically significant (p < 0.001). Mean ejaculatory latency time was
      significantly longer after circumcision (p < 0.001). In the light of our
      findings, we conclude that circumcision may contribute to sexual satisfaction by
      prolonging PEP latency but further studies are warranted also regarding the other
      dimensions of circumcision.

PMID- 19115672
TI  - Hemifacial spasm in correlation with electrophysiological and radiological
      findings.
AB  - OBJECTIVE: To investigate the correlation between the electrophysiological and
      radiological findings of primary hemifacial spasm patients. SUBJECTS: Patients
      with primary hemifacial spasm who had had no botulinum toxin treatment previously
      were included in the study. DESIGN: In this prospective study patients underwent
      cerebral magnetic resonance imaging,a magnetic resonance angiography
      investigation and an electrophysiological examination after informed consent had
      be given by the patients. The facial nerve distal latency, amplitude and blink
      reflex responses were recorded as well as clinical and demographic data. RESULTS:
      Twenty five patients completed radiological and electrophysiological
      investigations. The radiological investigations disclosed neurovascular
      compromise which can cause hemifacial spasm in twelve patients (48%) while the
      findings of two patients were not considered as a certain cause of hemifacial
      spasm. All patients except two had at least one electrophysiological abnormality
      (92%). The most frequent finding was an increased R1/D ratio which suggested an
      increased central conduction time. CONCLUSION: In this study, an increased R1/D
      ratio suggests that there is a functional impairment in the brain stem even if it
      is not possible to disclose structural abnormalities in some hemifacial spasm
      patients. Combining magnetic stimulation may be a useful tool for further
      investigations. An inadequate radiological investigation might be the cause of
      relatively low radiological abnormalities in comparison with the
      electrophysiological ones.

PMID- 19115673
TI  - Mitoxantrone-related acute leukemia in two MS patients.
AB  - We report two new cases of mitoxantrone-related leukemia occurring in two
      patients with multiple sclerosis (MS), 14 and 18 months after the last infusion
      of the drug. One patient was successfully treated. We were able to collect 29
      other cases in the literature. Most of them were single reports but some were
      described within cohorts of mitoxantrone-treated MS patients. The incidence rate
      was 0.65% from all cohorts totalizing 2299 patients. Acute promyelocytic leukemia
      with the translocation t(15;17) was over-represented in the MS population in
      comparison with cancer patients also treated with mitoxanrone. The occurrence of
      leukemia was dose-independent and appeared with a mean delay of 20 months after
      the end of the treatment.

PMID- 19115675
TI  - Distal myasthenia gravis.
AB  - Myasthenia gravis (MG) characteristically involves ocular; bulbar, and proximal
      limb muscles. MG with predominant distal limb involvement is uncommon. We present
      a case of MG with distal, asymmetrical, upper limb involvement, seven years after
      disease onset.

PMID- 19115674
TI  - Acute ischaemic pontine stroke revealing lyme neuroborreliosis in a young adult.
AB  - We report the case of a 23-year-old male patient who suddenly developed right
      hemiparesis, cerebellar ataxia, dysarthria, and bilateral dysmetria. Brain
      magnetic resonance (MR) examination demonstrated hyperacute ischaemic lesions
      within the pons. CSF analysis revealed a high protein content, lymphocytic
      pleocytosis, and oligoclonal IgG bands not present in the serum. Elevated IgM and
      IgG anti-Borrelia burgdorferi antibodies were shown in both serum and CSF
      samples, associated with an intrathecal synthesis of these antibodies. Ischaemic
      CNS lesions have been rarely observed as the first manifestation of Lyme
      neuroborreliosis. The putative mechanism for parenchymal ischaemia is the local
      extension of inflammatory changes from meninges to the wall of penetrating
      arterioles.

PMID- 19115676
TI  - ANCA-related vasculitic neuropathy mimicking motor neuron disease.
AB  - Several conditions have been reported to mimic motor neuron disease (MND) and
      misdiagnosis remains a common clinical problem. Peripheral neuropathy is a
      classic feature of many vasculitic syndromes and in some patients it may be the
      only manifestation of vasculitis. We report a case of ANCA-related vasculitic
      neuropathy where the clinical presentation was suggestive of MND. A 42-year-old
      woman was admitted to our centre to confirm a diagnosis of MND made elsewhere.
      Clinical examination revealed postural tremor at the right hand, mild tongue
      atrophy with diffuse fasciculations and brisk tendon reflexes without other
      muscular weakness or atrophies. Electromyography demonstrated denervation in
      tongue and in the first dorsal interosseous of right hand ; motor evoked
      potentials disclosed normal central motor conduction time. Laboratory studies
      revealed only a mild increase of p-ANCA. A muscle biopsy showed a small
      inflammatory infiltrate around a vessel. The patient started high dosage of oral
      steroids. After one year of follow-up the patient suspended oral steroids,
      postural tremor of the right hand disappeared and tongue fasciculations were
      reduced. Vasculitis may mimic a MND, particularly in the absence of sensory
      involvement. Caution should be exercised in the clinical diagnosis of MND. Muscle
      biopsy is indicated in patient with atypical MND especially in those with an
      exclusive involvement of lower motor neuron.

PMID- 19115677
TI  - Volumetric analysis of a rhabdoid meningioma during preoperative follow-up. A
      case report.
AB  - The authors describe a case of rhabdoid meningioma (RM) in a 17-year-old boy that
      was determined by measuring the tumor volume during preoperative follow-up. The
      volume of the tumor located in the left occipital lobe, was measured every 1-5
      months, using an image analysis software. The tumor volume doubling time (Td)
      ranged from 1.0 to 4.9 years in the first 11 months, but became 0.3 years in the
      last two months. The tumor grew rapidly in the last two months at which time
      surgery was performed. Pathological examination of the surgical specimen showed
      that the tumor contained rhabdoid cells (RCs). RCs were heterogeneously
      distributed in the tumor admixed with spindle-shaped cells. The areas where RCs
      were predominant had malignant histological features, with necrosis and high
      proliferation indices, whereas the areas with few RCs lacked the malignant
      features. The tumor grew slowly in the initial phase, possibly because components
      with low proliferation rates occupied most of the tumor. The tumor began to grow
      rapidly when the malignant component containing abundant RCs became predominant.
      To the authors' knowledge, this is the first report monitoring the volumetric
      change of RM periodically. Our investigation indicated that volumetric analysis
      is useful to decide surgical intervention of the meningiomas with potential
      malignancy.

PMID- 19115678
TI  - Mount Fuji sign following otogenic meningitis.

PMID- 19115679
TI  - Sentinel node biopsy for ipsilateral breast cancer recurrence: a review.
AB  - The aim of this study was to review published reports on the feasability,
      results, and reliability of sentinel node biopsy in cases of ipsilateral
      recurrent breast cancer. A Medline search on publications from January 1999 to
      December 2007 and cross-references in published articles were looked for. We
      identified 16 reports on sentinel node biopsy in recurrent breast cancer,
      including a total of 287 patients. In 210/287 (73.2%) a sentinel node was
      identified, 77/210 (37.7%) had had previous axillary lymph node dissection and
      131 (62.3%) a previous sentinel node procedure. Aberrant lymphatic drainage,
      other than the ipsilateral axilla was noted in 68/210 (32.4%). Of these 16/68
      (23.6%) were located in the contralateral axilla. Of the removed contralateral
      axillary sentinel nodes 8/17 (47.1%) were invaded by cancer. We conclude that
      sentinel node biopsy in cases of recurrent ipsilateral breast cancer is feasible.
      In about one out of three cases drainage to the contralateral axilla with
      invasion in almost half the cases takes place. The therapeutical consequences of
      these findings need further study.

PMID- 19115680
TI  - A phase 2 trial of oral imatinib in patients with epithelial ovarian, fallopian
      tube, or peritoneal carcinoma in second or greater remission.
AB  - PURPOSE OF INVESTIGATION: To determine the effect of imatinib on progression-free
      survival in patients with epithelial ovarian cancer in second or greater complete
      clinical remission (CCR). METHODS: 35 patients were enrolled between 10/2002 and
      1/2005. Eligible patients received imatinib at 400 mg daily orally. RESULTS: One
      patient withdrew consent, and two patients received protocol therapy in first
      remission and were excluded. Five patients were removed for possibly related
      toxicity. No associations were seen between PDGF-R staining and PFS. CONCLUSIONS:
      Treatment with imatinib for patients with ovarian cancer in second CCR or greater
      did not prolong the PFS beyond the historical estimate.

PMID- 19115681
TI  - Weekly paclitaxel/5-fluorouracil followed by platinum retreatment for patients
      with recurrent ovarian cancer: a single institution experience.
AB  - PURPOSE: Since the prognosis of recurrent ovarian cancer patients is still poor,
      we need to establish a useful treatment strategy to achieve their long-term
      survival. We treated recurrent ovarian cancer patients with weekly paclitaxel
      (PTX)/5-fluorouracil (5-FU) followed by platinum retreatment to investigate its
      clinical efficacy in a preliminary manner. METHODS: Sixteen patients with
      recurrent ovarian cancer, pretreated with taxane and platinum, were treated with
      weekly paclitaxel (PTX)/5-fluorouracil (FU). PTX (80 mg/m2) on day 1, 8, and 15
      was combined with a bolus injection of 5-FU (500 mg/m2) on day 2, 9, and 16.
      Chemotherapy was given every four weeks. Patients with stable disease or
      progressive disease were subsequently retreated with a platinum-containing
      regimen. Response was evaluated by RECIST criteria or CA125 criteria. Toxicities
      were evaluated according to the National Cancer Institute-common toxicity
      criteria (NCI-CTC) version 3. RESULTS: Among five patients with sensitive
      disease, one of four patients with measurable tumor and one without measurable
      tumor responded to weekly PTX/5-FU. Among 11 patients with resistant disease,
      none of five patients with measurable tumor and three of six patients without
      measurable tumor responded to weekly PTX/5-FU. Overall objective response rate by
      weekly PTX/5-FU was 31.3% (5/16). Among 16 patients, 13 patients who showed no
      response or progressive disease (three with sensitive disease, ten with resistant
      disease) received platinum retreatment after weekly PTX/5FU. All three patients
      with sensitive disease and three of ten patients with resistant disease revealed
      response to platinum retreatment. Overall objective response rate by platinum
      retreatment after weekly PTX/5-FU was 46.2% (6/13). CONCLUSIONS: Weekly PTX/5FU
      followed by platinum retreatment could be a useful treatment strategy for
      recurrent ovarian cancer patients. We need to establish the standard treatment
      strategy for recurrent ovarian cancer patients with a poor prognosis.

PMID- 19115682
TI  - Audit of suspected chronic intestinal pseudo-obstruction in patients with
      gynecologic cancer.
AB  - PURPOSE: To describe chronic intestinal pseudo-obstruction (IPO) syndromes that
      occur after radiotherapy or chemotherapy (or both) for gynecologic cancer.
      METHODS: All 48 patients in the study population had a history of gynecologic
      cancer, treatment with radiotherapy or chemotherapy (or both), and suspected
      chronic IPO. The final diagnosis was based on clinical symptoms, radiographic
      imaging, motility studies, and surgical findings. Treatment was expectant for 27
      patients and surgical for 21. RESULTS: In six of the 21 surgical patients, the
      final diagnosis was mechanical obstruction. In the other 15, it was IPO syndrome:
      six had an idiopathic dysfunction (ID) and nine had a thick fibrinous coating
      (FC) on the serosal surface. Intestines of these 15 patients had patent lumens
      but decreased motility. The ID and FC groups differed in mean age, chemotherapy
      administration, and mean time from radiotherapy to surgery. Symptoms improved in
      67% of FC patients compared with 17% of ID patients. Among patients treated
      expectantly, symptoms improved in 50% of the ID patients and in 38% of the FC
      patients. Motility studies were useful for distinguishing ID from FC or
      mechanical obstruction. CONCLUSION: Clinical history and motility studies may
      assist in diagnosing IPO syndrome in gynecologic cancer patients treated with
      radiotherapy or chemotherapy (or both) and in identifying patients who might
      benefit from surgical intervention.

PMID- 19115683
TI  - Is the watch and wait approach adequate after comprehensive surgical staging in
      invasive stage I epithelial ovarian cancer? The Norwegian Radium Hospital
      experience.
AB  - OBJECTIVES: The aim of this study on stage I epithelial ovarian cancer (EOC) was
      to see if our different treatment policies after 1995, when lymph node staging
      and paclitaxel were introduced, have affected the survival, try to define risk
      groups for relapse and who should get adjuvant chemotherapy (AC). METHODS: A
      retrospective study based on record information from all patients with invasive
      EOC stage I operated at the Norwegian Radium Hospital (NRH) 1984-2001, in total
      252 patients. RESULTS: Total 5-year survival was 83 and 82%, respectively, in
      both time periods. We found age and histology to be significant prognostic
      factors for overall survival (OS) (p < 0.01). From 1995 survival was
      significantly better for those who had been properly staged than for the others
      (p = 0.02), with a 5-year survival rate of 87 vs 64%. Those who did not get
      chemotherapy but were staged, had a significantly better overall survival than
      those who were not (p = 0.02), with a 5-year survival of 93 vs 77%. In the period
      1995-2001 the patients who received no adjuvant treatment lived longer than those
      who underwent chemotherapy and/or radiotherapy (p = 0.03). In the first period
      17% had no adjuvant treatment vs 58% in the last. Patients in a high-risk group
      getting AC had a tendency toward better survival than those who did not (p =
      0.08). CONCLUSIONS: Patients with Stage I low and medium risk EOC do not need AC
      if properly staged. For the high-risk group the optimal AC has not yet been
      established.

PMID- 19115684
TI  - Polymorphisms of p53, GSTM1 and GSTT1, and HPV in uterine cervix adenocarcinoma.
AB  - OBJECTIVE: To analyze the participation of glutathione-S-transferase (GST) M1 and
      T1 polymorphisms associated or not with protein p53 polymorphism at codon 72 and
      in the presence of HPV in the carcinogenesis of uterine cervix adenocarcinoma.
      METHODS: Forty-three samples of uterine cervix adenocarcinoma were studied and 86
      samples of endocervical cells of women without tumors formed the control group.
      The presence of HPV was determined in order to genotype the isoforms of p53 at
      codon 72, GSTM1, GSTM1*0, GSTT1 and GSTT1*0 which were evaluated by the PCR
      method. RESULTS: HPV was present in 97.67% of the adenocarcinoma cases and in
      31.40% of the control group. Statistical analysis showed differences (p = 0.001)
      and an OR of 113.3 (CI 95%: 13.67-947.14). GSTT1 and GSTT1*0 analysis showed a
      significant difference between the groups (p = 0.001) with an OR of 4.58 (CI 95%:
      2.041-10.28) (p < 0.001) for the presence of GSTT1*0. When it was associated with
      HPV OR was 6.6 (CI 95%: 0.04-0.50). Analyses of p53 and GSTM1 and GSTM1*0 either
      alone or associated with HPV were not significant. CONCLUSION: The presence of
      GSTT1*0 increased the risk for uterine cervix adenocarcinoma development while
      the allele GSTT1 had a protective action. The other isoforms did not appear to
      participate in the carcinogenesis of uterine cervix adenocarcinoma.

PMID- 19115685
TI  - Serum adiponectin in relation to endometrial cancer and endometrial hyperplasia
      with atypia in obese women.
AB  - OBJECTIVES: The aim of this work was to compare concentrations of adiponectin in
      the serum of obese women with endometrial cancer, endometrial hyperplasia with
      atypia, and normal endometrium. METHODS: We enrolled 105 obese women treated at
      the Department of Gynecological Surgery and Oncology of Adults and Adolescents.
      The patients were allocated to groups depending on the histological diagnosis (R 
      endometrial cancer, P - polyps, K - normal endometrium). We subdivided group R
      depending on the stage and grade of cancer. RESULTS: Significantly lower
      concentrations of adiponectin were found in patients with endometrial cancer
      (mean 15.28 microg/ml) as compared with polyps (29.94 microg/ml, p < 0.001) or
      normal endometrium (22.7 microg/ml, p < 0.05). Stage of cancer had no significant
      effect on the adiponectin level. When cancer grade was compared, lower levels of
      adiponectin were observed in patients with G3 (12.86 microg/ml) than G1 (19.04
      microg/ml, p < 0.05). CONCLUSION: Reduced levels of adiponectin may represent an
      independent risk factor for endometrial cancer.

PMID- 19115686
TI  - Tamoxifen in women with breast cancer and mammographic density.
AB  - PURPOSE OF INVESTIGATION: To evaluate the effect of tamoxifen on mammographic
      density using a qualitative and a semiquantitative method. METHODS: Mammograms
      from 148 women treated for breast cancer before and after surgery were reviewed:
      68 were administered tamoxifen; 80 did not receive tamoxifen. The mammograms were
      classified in one of the four BIRADS density categories by two radiologists
      blinded to the treatment and by a computer-assisted method after digitizing
      images. RESULTS: At mammographic one-year-follow-up density was reduced in both
      groups and remained stable in the following years. A comparison of mammograms
      performed before surgery and after one year showed a statistically significant
      difference in density reduction between the tamoxifen and the non-tamoxifen
      treated group. Good agreement was obtained between the qualitative and
      semiquantitative method. CONCLUSION: Breast density reduction observed in women
      treated with tamoxifen may help in the detection of small tumors in dense breasts
      by means of reducing the masking effect of parenchyma.

PMID- 19115687
TI  - A 15-year report of pathological and benign ovarian tumors in teenagers.
AB  - The purpose of this retrospective study was to determine the frequency, clinical
      aspects and surgical management of ovarian masses in 52 adolescent patients, in
      whom surgery was deemed necessary, from 1991-2006. We considered age, symptoms,
      ultrasound investigations, CA 125 levels, family history, operative treatment,
      surgical complications tumor size, histopathological examinations, pregnancy rate
      and follow-up. Ovarian lesions in teenagers include a broad array of pathologic
      diagnoses that have variable and non-specific presenting symptoms. The most
      common presenting complaint was abdominal pain in 34 (65.4%). Forty-seven
      patients (90.4%) had benign lesions, two (3.8%) had borderline tumors and three
      patients had malignant lesions (5.8%). Most of the patients who wanted to
      conceive subsequently did so. For benign ovarian disorders the operation should
      be designed to optimize future fertility while in patients with malignancy,
      complete staging and resection of the lesion should be the first concern.

PMID- 19115688
TI  - Concurrent chemoradiation with carboplatin for elderly, diabetic and hypertensive
      patients with locally advanced cervical cancer.
AB  - INTRODUCTION: Chemoradiation based on cisplatin is the standard treatment of
      locally advanced cervical cancer, however, a subset of patients are either
      elderly and/or have comorbidities such as diabetes and hypertension. These
      conditions may compromise the administration of cisplatin. We report our
      Institution experience with weekly carboplatin as a radiosensitizer for the
      management of this subset of patients. PATIENTS AND METHODS: We reviewed the
      files of 59 patients with locally advanced cervical cancer who were treated with
      primary chemoradiation with weekly carboplatin. Response rate, toxicity and
      survival were analyzed. RESULTS: Mean age was 62 years (range, 36-83 years). The
      majority of cases were squamous cell carcinoma (88.14%), and distribution
      according to FIGO Stage was IB2 8.4%, IIA 13.5%, IIB 52.5%, IIIA 3.3% and IIIB
      18.6%; Overall, 100% and 91% of patients completed external beam and
      intracavitary therapy. Seventy-nine percent received from five to six planned
      cycles of weekly carboplatin. Complete responses were achieved in 49 (83.05 %)
      patients, whereas ten patients (16.95%) had either persistent or progressive
      disease. The most common toxicities were grades 1 and 2 hematological and
      gastrointestinal. At median follow-up (20 months; range 2-48 months), 16 patients
      (32.65%) have relapsed. Estimated 30-month overall survival is 63%. CONCLUSIONS:
      Weekly carboplatin concurrent with pelvic radiation is well tolerated in patients
      with locally advanced carcinoma of the cervix who are older than 70 years and/or
      have diabetes mellitus and/or high blood pressure, however, the apparently
      slighty lower survival observed cautions against its routine use.

PMID- 19115689
TI  - Preoperative transforming growth factor-beta 1 (TGF-beta 1) plasma levels in
      operable breast cancer patients.
AB  - OBJECTIVES: The aim of this project was to search for new risk prognostic markers
      in the early stage of breast cancer. We tested preoperative plasma transforming
      growth factor - beta 1 (TGF- beta 1) levels in patients with operable breast
      cancer. Correlation with traditional prognostic markers and with
      positivity/negativity sentinel lymph node was evaluated. MATERIALS AND METHODS:
      Between 2003 and 2005, 36 patients with operable breast cancer (T1-2, N0-1, M0)
      with positive or negative sentinel lymph nodes were evaluated for their plasma
      TGF-beta 1. Twenty-seven healthy individuals (9 premenopausal and 18
      postmenopausal) served as controls. Patients were evaluated for the traditional
      prognostic markers including tumor characteristics, positivity and negativity of
      sentinel lymph node, TNM, tumor grade, expression of tumor markers CA 15-3 and
      CEA, hormonal status (pre- or postmenopausal patients, estrogen and progesteron
      receptor expression), ERB and p53 expression. Predictive value of TGF-beta 1
      level and correlation with either of the assessed parameters was tested by one
      way ANOVA analysis. RESULTS: Measurements of preoperative plasma TGF-beta 1
      levels in patients with operable breast cancer were significantly higher compared
      with healthy individuals (median 15293 and 3983 pg/ml p < 0.0001). TGF-beta 1
      level in plasma of patients with a positive sentinel lymph node was significantly
      higher than in patients with negative sentinel lymph nodes (high vs low, median
      18,9 and 14,5 ng/ml, respectively, p = 0.05). CONCLUSION: The determination of
      TGF-beta 1 status might help to identify a high-risk population early in tumor
      progression, for which a more appropriate therapy should be established. In the
      node-negative population, the up-regulation of TGF-beta 1 might constitute an
      early event that promotes further progression of breast tumors.

PMID- 19115690
TI  - The effect of combined therapy on activity of cathepsin D and alpha-1-antitrypsin
      in the blood serum of women with cervical cancer.
AB  - PURPOSE OF INVESTIGATION: The aim of the study was to determine the activity of
      cathepsin D (CTSD) and alpha-1-antitrypsin (AAT) in the blood serum of women with
      cervical carcinoma treated with different modes of therapy. METHODS: The study
      was conducted on 68 women suffering from carcinoma of the uterine cervix, that
      were irradiated intracavitarily by a Selectron LDR brachytherapy unit.
      Additionally, all patients were treated with different therapy methods according
      to clinical stage. RESULTS: In women with cervical cancer, CTSD activity was
      higher while AAT activity was lower both before and after brachytherapy sessions
      as compared to controls. Six months after the end of therapy, the activity of
      CTSD and AAT reverted back to the values characteristic for healthy women.
      CONCLUSION: The estimation of cathepsin D and alpha-1-antitrypsin activity during
      the course of cervical cancer management may be useful in early detection of
      potential recurrence and/or widespread metastasis formation.

PMID- 19115691
TI  - Tragic results of suboptimal gynecologic cancer operations.
AB  - OBJECTIVE: The goal of this study was to analyze gynecological cancer patients
      who underwent suboptimal or failed surgeries with unsatisfactory and undesired
      results. STUDY DESIGN: During 1997-2007, 74 women were referred to our
      gynecological oncology service after suboptimal or failed surgeries for ovarian,
      cervix, endometrium and vulvar cancers. Medical records were evaluated
      retrospectively to determine the reasons of suboptimal surgery. RESULTS: Optimal
      cytoreduction was achieved in ten women (21.7%), 32 women (69.5%) had suboptimal
      surgical cytoreduction and four women (8.6%) had failed surgery, Seven patients
      were recurrences (3 had liver metastasis, 2 had pelvic metastasis, 2 had bladder
      metastasis); two patients died due to bladder metastasis, one patient died six
      days after surgery due to a pulmonary embolism in the suboptimal cytoreduction
      group, and one patient died due to ascites in the failed surgery group. Optimal
      surgery was achieved in three women (27.2%) and eight women (72.7%) had
      suboptimal surgery in the cervical cancer population. One patient had a
      recurrence with pelvic metastasis in the suboptimal group. Suboptimal surgery was
      achieved in one woman with vulvar cancer. Optimal surgery was achieved in seven
      women (43.7%) and nine women (56.2%) had suboptimal surgery in the endometrial
      cancer population. One patient died 11 days after surgery due to sepsis in the
      optimal surgery group. One patient died 21 months after primary surgery and the
      other patient had a recurrence with paraaortic lymph nodes, ascites and omental
      thickening in the suboptimal surgery group. The prognosis of 30 (65.2%) women in
      the ovarian cancer population, eight (72.7%) women in the cervical cancer group,
      11 (68.7%) women in the endometrial cancer group, and one woman (100%) in the
      vulvar cancer population was unknown. The unknown cases of all genital cancers
      were missed during followup and we could not reach them using their phone or
      address information. CONCLUSION: If a gynecologist does not have enough
      experience or expertise about gynecological cancer operations, he or she must
      consider the possible harm that any surgical intervention might do, as the latin
      phrase "primum non nocere" means and should refer patients to a gynecological
      oncology center without performing any surgery. Optimal gynecologic surgery can
      only be carried out correctly when education becomes available throughout the
      world. Thus postgraduate fellowship programs should be considered urgently to
      extend the general gynecologists' surgical experience and expertise in developing
      and undeveloped countries.

PMID- 19115692
TI  - Clinical audit of patients with cervical cancer in Slovenia. Data analysis from
      2003-2006.
AB  - PURPOSE OF INVESTIGATION: From 2003 to 2006 the data on Slovenian cervical cancer
      patients who regularly attended a gynecologist were gathered. Data were analyzed
      in order to improve the efficiency of the cervical cancer screening program.
      METHODS: Data on all patients newly diagnosed with cervical cancer were collected
      at three central clinics in Slovenia. The results are a presentation and
      comparison of detailed information on some characteristics of cervical cancer
      patients of the group that regularly visited a gynecologist and of the other
      group who did not. Data were processed by descriptive epidemiological methods.
      Mantel-Haenzel chi2 and Fisher's p tests were used to evaluate statistical
      significance. RESULTS: On average, 55% of patients with cervical cancer underwent
      a gynecological examination five years before the diagnosis. The patients who
      regularly attended their gynecologist were, in all age groups, statistically
      significantly younger, the stage of cervical cancer at diagnosis was
      statistically significantly lower (p = 0.01) and were, in statistically
      significantly higher percentage, treated surgically (p < 0.01). From 2003 to
      2006, each patient had on average five examinations at her gynecologist within
      the period of five years to six months before the diagnosis of cervical cancer.
      The average number of collected smear samples was 3.2. CONCLUSION: From the
      results of our analysis, it may be concluded that improvements are needed in
      Slovenia in the field of screening for and early detection of cervical cancer.

PMID- 19115693
TI  - Uterine sarcoma diagnosed during colon surgery--a complete precise diagnosis.
AB  - Uterine sarcomas are very rare tumors with the greatest malignant potential of
      all uterine tumors, and they differ significantly from endometrial carcinoma by
      their specific course, propagation and prognosis. A 54-year-old patient, after
      three vaginal deliveries and negative personal and family history, as well as
      regular cycles, presented with secondary problems related to occasional
      constipation with sporadic diarrhea and bloody stools. Colonoscopy revealed a
      colon tumor.

PMID- 19115694
TI  - Malignant germ cell tumors of the ovary: a review of 41 cases and risk factors
      for recurrence.
AB  - OBJECTIVE: To review the outcome of treatment in patients with malignant ovarian
      germ cell tumors and to define the risk factors for recurrence. MATERIAL AND
      METHODS: Forty-one patients with malignant ovarian germ cell tumors were reviewed
      retrospectively. Survival time and survival rate were obtained. Risk factors such
      as stage, histological type, and type of operation were evaluated for
      reccurrence. RESULTS: Twenty-three (56%) had dysgerminomas, eight (19.5%) had
      mixed germ cell tumors, three (7.3%) had yolk sac tumors, three (7.3%) had
      immature teratomas, two (4.8%) had squamous cell carcinoma arising from a mature
      teratoma, one (2.4%) had embryonal carcinoma and one choriocarcinoma. Most of the
      cases (73%) were in Stage I. Twenty-nine patients (70.7%) underwent conservative
      surgery and 12 patients (29.3%) had at least bilateral salpingo-oophorectomy.
      Thirty patients were operated on optimally with surgical staging and 11
      suboptimally. Seven patients (17%) had recurrence after remission. The overall
      survival time was 187 +/- 8.43 months for all cases, 195 +/- 8.49 for
      dysgerminoma and 161 +/- 10.96 for non-dysgerminoma cases with a median follow-up
      time of 98.52 (8-204) months. Non-dysgerminoma histologic type, being operated on
      suboptimally and radically, and advanced tumor stage have been found to be risk
      factors for recurrence. CONCLUSION: Regardless of histologic types and stages the
      prognosis of germ cell tumors are satisfactory with current therapeutic
      strategies.

PMID- 19115695
TI  - Fascin can be an auxiliary immunomarker of ovarian granulosa cell tumors:
      comparison with calretinin and inhibin-alpha.
AB  - The histopathologic diagnosis of granulosa cell tumor adult type (AGCT) can be
      supported by the use of established immunomarkers such as inhibin-alpha and
      calretinin. Previously unreported data is presented on the detection of fascin in
      AGCT, in nonneoplastic granulosa cells and in other types of sex-cord stromal
      tumors. In addition, by staining a panel of various tumors, potentially included
      in the differential diagnosis of AGCT, we assessed the value of fascin as an
      auxiliary AGCT immunomarker. Intense and strong fascin staining may assist in
      cases with ambiguous calretinin or inhibin-alpha staining. On the contrary,
      absence of fascin should question a provisional morphologic diagnosis of AGCT.

PMID- 19115696
TI  - Abdominal pillow for the sparing of small bowel in four-field conventional pelvic
      radiotherapy.
AB  - From 2003 through 2004, 88 patients with gynecological cancer were referred to
      Istanbul University Oncology Institute for pelvic radiation therapy. All patients
      underwent small bowel evaluation within the pelvic radiotherapy field in both the
      supine and prone positions with and without an abdominal pillow. The small bowel
      area included in radiation fields and intestinal movement were compared on PA
      films. All patients were treated by using the abdominal pillow. The median
      external beam pelvic radiation dose of 5040cGy (range, 3220-5400cGy) was
      administered. The mean distance of upward displacement of small bowel in the
      prone position on abdominal pillow compared with in the prone position alone and
      in the supine position was 3.6 cm (range, 0-14 cm) and 4.7 cm (range, 0-14 cm).
      Using the abdominal pillow, the mean small bowel area was reduced by 45% and 55%
      compared to the prone position alone and the supine position, respectively (p =
      0.0001). In patients who had pelvic surgery intestinal movement was significantly
      reduced. The incidence of G1, G2 and G3 acute radiation toxicity was 18%, 36% and
      3%, respectively. This study demonstrates that the small intestines can be
      displaced out of the radiation field by an abdominal pillow in the prone
      position. Also, this noninvasive technique provides for reduction of acute
      gastrointestinal morbidity.

PMID- 19115697
TI  - Ovarian malignant immature teratoma associated with pregnancy--a case report.
AB  - We report the case of a malignant immature teratoma diagnosed at 21 weeks of
      amenorrhea in a 36-year-old healthy woman. Ultrasound examination showed a
      multilocular cystic mass of 175 mm in diameter, situated on the left side of the
      uterus. A left ovariectomy was performed by laparotomy at 22 weeks of amenorrhea.
      Histologic examination revealed a malignant grade 2 immature teratoma, and the
      patient underwent three courses of chemotherapy with a good pregnancy outcome. A
      cesarean section was carried out at 39 weeks of amenorrhea, associated with a
      left salpingectomy on which the pathologist examination did not find any
      malignant cells. The newborn had a normal aspect, and the mother was considered
      to be in remission after two more courses of chemotherapy..

PMID- 19115699
TI  - Ectopic breast cancer in the anterior chest wall: a case report and literature
      review.
AB  - Ectopic breast cancer is rare and when situated in the chest wall, it is even
      rarer. This report describes the case of an 86-year old Brazilian woman with a
      palpable carcinoma, located in the right inframammary fold, and right axillary
      adenopathy. The patient was submitted to excision of the accessory breast and to
      right axillary lymphadenectomy. All 28 resected lymph nodes contained metastatic
      cells. Diagnosis and treatment of ectopic breast cancer should be carried out
      early in view of its aggressivity.

PMID- 19115698
TI  - Squamous cell carcinoma of the vulva in a young woman with Crohn's disease.
AB  - BACKGROUND: Crohn's disease is a chronic inflammatory disorder of the
      gastrointestinal tract. Because Crohn's disease is transmural it may form
      fistulas to adjacent structures, including the perineum and vulva. CASE: A 28
      year-old white female with a history of Crohn's disease presented with a non
      healing vulvar fistula. Biopsy revealed squamous cell carcinoma. CONCLUSION:
      Young women may develop squamous cell carcinoma associated with fistulae of
      Crohn's disease.

PMID- 19115700
TI  - Primary endometrial B-cell lymphoma: case report.
AB  - The female genital tract is usually involved with lymphoma as part of
      disseminated disease. Primary lymphoid neoplasms of the female genital tract are
      rare; the frequency was reported to be 2% among extranodal lymphomas in women.
      Most of the time, primary female genital tract lymphoma occurs in the ovary and
      cervix, whereas endometrial lymphoma is extremely rare. The case of an 89-year
      old patient that presented with postmenopausal bleeding is reported. An
      endometrial polypoid formation was found on hysteroscopic examination and the
      biopsy revealed a diffuse large B-cell lymphoma. Total abdominal hysterectomy and
      bilateral salpingo-oophorectomy were surgically performed. The histologic
      diagnosis was primary diffuse large B-cell lymphoma of the endometrium. Adjuvant
      therapy was not performed. Five months after initial diagnosis, the patient died.
      Only a few case reports of primary endometrial lymphoma have been published;
      therefore, information concerning etiologic factors, histologic type, treatment
      and prognosis is limited.

PMID- 19115701
TI  - Sclerosing stromal tumor of the ovary: a case report.
AB  - A case of a rarely occurring ovarian tumor, sclerosing stromal tumor of the
      ovary, in an 11-year-old girl treated laparoscopically is described.

PMID- 19115702
TI  - Conservative management of a patient with endometrial carcinoma desiring
      fertility: how to inform?
AB  - Conservative management of patients with endometrial cancer who desire fertility
      is becoming widespread in certain circumstances. A 36-year-old women desiring
      fertility with early-stage endometroid type adenocarcinoma of the endometrium was
      treated with 160 mg/d megestrol acetate for six months. After confirmation of a
      normal endometrial biopsy she became pregnant spontaneously. Following an
      uneventful pregnancy a healthy baby at term was delivered by cesarean section.
      Definitive surgery was performed. The risks and benefits of this thereupeutic
      approach are discussed and informing style of the patients emphasized.

PMID- 19115703
TI  - Life-saving hysterectomy in choriocarcinoma: presentation of two cases.
AB  - BACKGROUND: Choriocarcinoma is a malignant tumor of the placenta. Life-saving
      hysterectomy was performed in two cases with choriocarcinoma who had profuse
      vaginal bleeding. CASE 1: A 25-year-old, gravida 3, para 1, woman was referred to
      our emergency clinic with the diagnosis of choriocarcinoma and massive vaginal
      bleeding. She had been transfused seven units of blood at the hospital where she
      was first admitted. Pelvic examination demonstrated heavy vaginal bleeding and a
      uterus equivalent to the size of 14 weeks of gestation. Her beta-hCG level was
      560,000 mIU/ml. Despite four units of blood transfusion, she had a pulse rate of
      130/min, arterial pressure of 90/60 mm/Hg and HCT of 19%. An emergency
      hysterectomy with vertical incision was performed. CASE 2: A 54-year-old, gravida
      3, para 3, woman was referred to our clinic with heavy bleeding with the
      diagnosis of choriocarcinoma. She was scanned to look for possible metastases and
      pulmonary metastasis was detected. Chemotherapy was planned but as sudden vaginal
      bleeding began she was referred to the Gynecology Department. At pelvic
      examination a soft uterus the size of 20 weeks of gestation was palpated. The
      beta-hCG level was 554,700 mIU/ml. Due to hemodynamic instability and continuous
      vaginal bleeding an emergency hysterectomy was performed. CONCLUSION: Although
      chemotherapy is the cornerstone of treatment for choriocarcinoma, optimal
      treatment results may depend on the addition of surgery in selected
      circumstances. Hysterectomy is indicated in cases with life-threatening
      hemorrhage.

PMID- 19115704
TI  - Metastasis from breast carcinoma to endometrial polyp.
AB  - Metastasis of a breast carcinoma to an endometrial polyp is extremely rare, with
      only ten cases having been reported in the literature up to now. We present the
      case of a 60-year-old woman with invasive ductal carcinoma who complained of
      vaginal bleeding. She underwent hysteroscopy with biopsy. Microscopic examination
      revealed an endometrial polyp which contained foci of adenocarcinoma. The
      morphologic features of the tumor were identical to the original breast
      carcinoma.

PMID- 19115705
TI  - Sign of the times.

PMID- 19115707
TI  - 2009 procedure code preview.

PMID- 19115706
TI  - Caregiving stress.

PMID- 19115708
TI  - Impact of RIS/PACS integrated speech recognition on report availability.
AB  - First adopted by radiology more than 25 years ago, speech recognition (SR)
      technology has been significantly improved. State-of-the-art SR systems are
      characterized by extensive vocabularies and advanced mathematical language models
      which theoretically allow for mean recognition rates far beyond 90%. Commercial
      arguments for SR implementation are a reduction of report turnaround times (RTT)
      and cost savings by the elimination of transcriptionist services. In contrast,
      the (potential) negative impact of front-end SR on radiologists' productivity has
      been discussed extensively in the literature. This study was conducted in a 1400
      bed university hospital and aims to retrospectively evaluate the effect of an SR
      system on report availability and RTT over a 1.5 year period after integration
      into a preexisting RIS/PACS installation. Front-end SR with editing of the draft
      report by the radiologist (night and weekend reports) and back-end SR with
      correction of the draft report (put out by the recognition servers) by
      transcriptionists (reports generated during routine working time) were utilized.

PMID- 19115709
TI  - Insurance contracting for the imaging center: things nobody tells you.

PMID- 19115710
TI  - Qualities that foster cohesive teams.
AB  - The radiology manager can be influential in promoting group cohesiveness within
      the department. Identifying qualities that radiology managers believe to be
      descriptive of cohesive work teams could be very informative for other radiology
      managers. The surveyed radiology managers had a positive perception of their work
      groups based on the factors that promote cohesion and achievement. The survey
      instrument developed has high internal correlation for future use with other
      radiology managers and employee groups. Continued research is needed to determine
      if these group results are indicative of the larger field of radiology management

PMID- 19115711
TI  - Going green.

PMID- 19115712
TI  - Coding and billing for radiology physician extenders.
AB  - Correct coding and billing for services provided by physician extenders can be
      challenging and complex and it is critical that organizations perform these
      functions correctly to ensure compliance. Incident-to is the only provision that
      allows physicians to charge and be paid for services that they did not directly
      perform. It is important that individuals responsible for charge capture
      understand how incident-to may or may not apply in their organization. What
      extenders are allowed to do in their scope of service may not coincide with what
      is allowed from a billing perspective.

PMID- 19115713
TI  - Implementing volume ultrasound workflow.
AB  - Ultrasound departments are consistently challenged with increasing patient loads,
      backlog/access, repetitive stress injuries, operator dependent technology, and
      the recruitment and retention of qualified sonographers. The value of the volume
      ultrasound workflow will dramatically enhance the operations of any ultrasound
      department. Although change is always a stressful transition for everyone
      involved, perserverance will lead to great rewards and will benefit all personnel
      involved. Sonographers currently using this new workflow model state they will
      never turn back to the traditional 2D stillframe repetitive imaging from the
      ability to reconstruct volumes and visualize in the 3 orthogonal planes.
      Together, volume imaging workflow and structured reporting will shift work from
      the scan rooms and radiologist reading rooms to a central workstation. This
      technology is truly changing the traditional and less efficient workflow of the
      ultrasound department to a more consistent and easier way of working.

PMID- 19115714
TI  - Capital budgeting: the characteristics of imaging projects, part 1.

PMID- 19115715
TI  - Graduation day.

PMID- 19115716
TI  - A fairy tale--or is it?

PMID- 19115717
TI  - Lead in Christmas lights.
AB  - A recent California proposition led to awareness that lead is a stabilizer in the
      Polyvinyl Chloride (PVC) jacketing that covers conductors in Christmas lights.
      The objective of this study is to examine the level of accessible lead in
      Christmas lights. Following U.S. Environmental Protection Agency (U.S. EPA) Lead
      Inspectors' procedures, researchers at Cornell University and in Nebraska
      conducted wipe samples and total lead content samples of newly purchased and
      older Christmas light sets. Samples were analyzed for lead content. Lead was
      present in varying amounts on all samples. The amount of lead from the Nebraska
      samples, normalized to length of strings, was independent of analyzing
      laboratory, analysis method, age of string, and repeat sampling, both immediately
      and after extended storage. A later analysis of these same strings by the Cornell
      team showed diminished quantities. Amounts of surface lead normalized to crude
      estimates of the area of light string indicated surface concentrations in excess
      of U.S. EPA clearance level for lead on window sills. Whether exposure to lead in
      Christmas lights affects blood lead levels in humans is unknown. No standards
      exist for lead content in this product, and no protocols exist for conducting
      tests on it. Therefore, consumers may wish to exercise caution to reduce possible
      exposure.

PMID- 19115718
TI  - Manganese in Madison's drinking water.
AB  - Public concern over events of manganese-discolored drinking water and the
      potential for adverse health effects from exposure to excess manganese reached a
      high level in 2005. In response, Public Health Madison Dane County, together with
      the Madison Water Utility, conceived and implemented a public health/water
      utility strategy to quantify the extent of the manganese problem, determine the
      potential for adverse human health effects, and communicate these findings to the
      community. This strategy included five basic parts: taking an inventory of wells
      and their manganese levels, correlating manganese concentration with turbidity,
      determining the prevalence and distribution of excess manganese in Madison
      households, reviewing the available scientific literature, and effectively
      communicating our findings to the community. The year-long public health/water
      utility strategy successfully resolved the crisis of confidence in the safety of
      Madison's drinking water.

PMID- 19115719
TI  - The effects that well depth and wellhead protection have on bacterial
      contamination of private water wells in the Estes Park Valley, Colorado.
AB  - Over the past five years, it is estimated that 10% of residential water wells
      have tested positive for total coliform and 2% for E.coli bacteria in the Estes
      Park Valley, Colorado. Many of these water wells are shallow or hand-dug in
      construction. In this study, samplings of 30 private untreated water wells were
      tested for total coliform bacteria in the Estes Park Valley. Water wells were
      classified into three categories for well depth (<99 feet [30.2 m], 100-199 feet
      [30.5-60.7 m], and >200 feet [61 m]) and for wellhead protection (poor, fair, and
      good). Results indicated that 71% of the wells less than 199 feet (60.7 m) tested
      positive for total coliform (chi2 = 15.559, p < .0001). Also, 71% of wells
      classified as having poor and fair wellhead protection tested positive for total
      coliform (chi2 = 13.084, p = .001). This study determined that wellhead
      protection and well depth does play a role in bacterial contamination of water
      wells.

PMID- 19115720
TI  - Drinking grandma: the problem of embalming.
AB  - The modern practice of embalming replaces organic blood with various toxic and
      carcinogenic chemicals, particularly formaldehyde. Then the embalmed body is
      placed underground where, despite the casket, the body's fluids will inevitably
      leak into the groundwater. Alternatively, the body may be burned, releasing
      chemicals into the air. The initial reasons for the use of embalming and the
      rationale given for the continuance of the practice fail to justify the potential
      public health and environmental risks presented by embalming.

PMID- 19115721
TI  - Evaluating citizen attitudes and participation in solid waste management in
      Tehran, Iran.
AB  - Recently, increasing attention has been paid to the environmental impact of solid
      waste in Iran. Consequently, solid waste management has become a remarkably
      important issue. Solid waste comprises a wide range of materials and comes from a
      variety of sources. Having a population of about 10 million (about 1/7 of Iran's
      total population), Tehran is among the most populated capitals in the world. With
      22 different districts, this city generates approximately 7,000 metric tons of
      municipal waste per day that culminates in a total of 2.5 million tons annually.
      If no reduction strategy on the waste stream is implemented, this huge amount of
      waste will be buried in Kahrizak (the exclusive landfill site of Tehran). Land
      and underground water resource degradation in the vicinity of the landfill site
      as well as disease outbreaks in the area surrounding the site may be considered
      alarming warnings for further catastrophic consequences of uncontrolled waste
      dumping. In this study, the composition of Tehran's solid wastes is analyzed. In
      order to physically analyze waste generated, waste sampling was carried out by
      trained workers of the Tehran organization of waste recycling and compost in 2004
      for 10 successive days in the middle of each of four seasons. As a result of the
      study, some practical recommendations are made to reduce the waste stream load
      directed toward the land. Furthermore, this study evaluated people's concern
      about the fate of the waste they generate. According to the data collected in a
      survey, citizens' participation is not remarkably high, but even the modest
      cooperation recorded may cause a great benefit if extrapolated to the whole city.
      By virtue of sharp decreases in the cost of total waste collection and transport,
      as well as the benefits of land and underground water resource preservation,
      separation of wastes at their source by individual households makes economic
      sense.

PMID- 19115722
TI  - Pollution and sanitation problems as setbacks to sustainable water resources
      management in Freetown.
AB  - The civil conflict in Sierra Leone (1991-2001) caused a dramatic increase in the
      population of Freetown. This population increase overstretched housing
      facilities, leading to the creation of camps and many squatter settlements with
      poor sanitation practices. Overcrowding has become a serious concern in light of
      the acute water shortage that struck Freetown in May and June 2006. Some of the
      numerous small water bodies that could have been used to augment the public water
      supply were contaminated by the disposal of solid and industrial waste and poor
      sewage management. Improper disposal practices have a direct impact on public
      health. This paper recommends addressing the policy gap, establishing clear
      threshold criteria for all water bodies and wastewater discharge, and integrating
      the above issues in the ongoing review process of draft water sanitation policy.
      Public education of the negative consequences of poor waste management practices
      on water quality and public health can also positively affect general sanitation
      practices

PMID- 19115723
TI  - Enhancing and revitalizing environmental public health.

PMID- 19115724
TI  - Community testing: a commentary.

PMID- 19115725
TI  - Salmonella Saintpaul: what went wrong?

PMID- 19115726
TI  - Denver environmental health tries a new approach: community-based social
      marketing.

PMID- 19115727
TI  - FDA clears new CDC test to detect human influenza.

PMID- 19115728
TI  - New "nano-positioners" may have atomic-scale precision.

PMID- 19115729
TI  - NEHA and the economy.

PMID- 19115730
TI  - Record limbo. Hybrid systems add burden and risk to data reporting.
AB  - Maintaining dual paper and electronic systems is often a necessity in the
      transition to digital record systems. The challenge in reporting data is keeping
      track of what data reside where.

PMID- 19115731
TI  - Planning forms automation. A carefully crafted project plan is the first step in
      achieving expectations and lasting value from electronic forms management.

PMID- 19115732
TI  - Minimizing hybrid records. Tips for reducing paper documentation as new systems
      come online.
AB  - It can be tempting for providers to reach for paper, especially when things get
      hectic. Planning and support help keep the hybrid record from getting more hybrid
      than it has to be.

PMID- 19115733
TI  - Health IM and health IT. Frequent traveling companions.

PMID- 19115734
TI  - Tools of the E-discovery trade. Taxonomy fundamentals for managing document
      management systems.

PMID- 19115735
TI  - Help in setting access controls. Using the HL7 RBAC Healthcare Permission Catalog
      to reduce data breaches.

PMID- 19115736
TI  - Is document imaging the right choice for your organization?

PMID- 19115737
TI  - Practice brief. HIM and Health IT. Discovering common ground in an electronic
      healthcare environment.

PMID- 19115738
TI  - Practice brief. Management practices for the release of information.

PMID- 19115739
TI  - The ABCs of Medicare Advantage.

PMID- 19115741
TI  - Perpetual medical politics.

PMID- 19115740
TI  - FY 2009 hospital IPPS final rule.

PMID- 19115742
TI  - HIV prevention and transmission the focus at International AIDS Conference.

PMID- 19115743
TI  - Media 'knight' breathes life into paediatric ICUs.

PMID- 19115744
TI  - Metanalysis critical of blood alternative product challenged.

PMID- 19115745
TI  - AIDS reality bedevils social security plans.

PMID- 19115746
TI  - Has HIV prevalence peaked in South Africa?--Can the report on the latest
      antenatal survey be trusted to answer this question?

PMID- 19115747
TI  - Clinical excellence and the NICEties of value-based priority setting.

PMID- 19115748
TI  - Neonatal circumcision does not reduce HIV/AIDS infection rates.

PMID- 19115749
TI  - The nervous system in antiquity.

PMID- 19115750
TI  - Zimbabwe: a crossroads for the health professions.

PMID- 19115751
TI  - Rheumatic heart disease: social and economic dimensions.

PMID- 19115752
TI  - Rolling out male circumcision as a mass HIV/AIDS intervention seems neither
      justified nor practicable.

PMID- 19115753
TI  - Imaginary bugs, real distress: delusional parasitosis.

PMID- 19115754
TI  - HIV prevention needs to confront the elephant on the road.

PMID- 19115755
TI  - Namaqua dwarf adder (Bitis schneideri) envenomation.

PMID- 19115756
TI  - Male circumcision and its relationship to HIV infection in South Africa: results
      of a national survey in 2002.
AB  - OBJECTIVE: To investigate the nature of male circumcision and its relationship to
      HIV infection. METHODS: Analysis of a sub-sample of 3 025 men aged 15 years and
      older who participated in the first national population-based survey on HIV/AIDS
      in 2002. Chi-square tests and Wilcoxon rank sum tests were used to identify
      factors associated with circumcision and HIV status, followed by a logistic
      regression model. RESULTS: One-third of the men (35.3%) were circumcised. The
      factors strongly associated with circumcision were age > 50, black living in
      rural areas and speaking SePedi (71.2%) or IsiXhosa (64.3%). The median age was
      significantly older for blacks (18 years) compared with other racial groups (3.5
      years), p < 0.001. Among blacks, circumcisions were mainly conducted outside
      hospital settings. In 40.5% of subjects, circumcision took place after sexual
      debut; two-thirds of the men circumcised after their 17th birthday were already
      sexually active. HIV and circumcision were not associated (12.3% HIV positive in
      the circumcised group v. 12% HIV positive in the uncircumcised group). HIV was,
      however, significantly lower in men circumcised before 12 years of age (6.8%)
      than in those circumcised after 12 years of age (13.5%, p = 0.02). When
      restricted to sexually active men, the difference that remained did not reach
      statistical significance (8.9% v. 13.6%, p = 0.08.). There was no effect when
      adjusted for possible confounding. CONCLUSION: Circumcision had no protective
      effect in the prevention of HIV transmission. This is a concern, and has
      implications for the possible adoption of the mass male circumcision strategy
      both as a public health policy and an HIV prevention strategy.

PMID- 19115757
TI  - Symptomatic hyperlactataemia in adults on antiretroviral therapy: a single-centre
      experience.
AB  - OBJECTIVE: There are limited data on symptomatic hyperlactataemia caused by
      antiretroviral therapy (ART) in resource-limited settings. We assessed
      individuals who developed symptomatic hyperlactataemia on ART in an outpatient
      clinic in South Africa. DESIGN: A retrospective record review was performed on
      patients attending the clinic from January 2004 to December 2005. RESULTS: Thirty
      five patients, all on stavudine-containing regimens, developed symptomatic
      hyperlactataemia. The incidence in this population was 20.5 cases per 1 000
      person-years of ART with an associated mortality of 21%. The major risk factor
      was being female (risk ratio (RR) 3.27). Significant clinical symptoms preceding
      symptomatic hyperlactataemia include nonspecific gastrointestinal symptoms,
      weight loss, and development of symptomatic neuropathy. CONCLUSIONS: The
      incidence of symptomatic hyperlactataemia in our population was high. Simple
      clinical measures, such as neuropathy symptoms and monitoring of weight, may
      alert the clinician to impending symptomatic hyperlactataemia. Early diagnosis
      expedites safe outpatient care and switching of ART regimens without
      interruption, in many cases.

PMID- 19115758
TI  - Surgical complications of bacille Calmette-Guerin (BCG) infection in HIV-infected
      children: time for a change in policy.
AB  - AIM: Bacille Calmette-Guerin (BCG) immunisation is well established as part of
      the South African national expanded programme for immunisation (EPI). The World
      Health Organization (WHO) currently recommends that BCG be given to all
      asymptomatic infants irrespective of HIV exposure at birth but does not recommend
      BCG vaccination for children with symptomatic HIV infection. This approach,
      however, has led to HIV-infected neonates who are asymptomatic at birth,
      developing severe vaccine-related complications. We present a surgical case
      series, representative of a minority of the cases in circulation, in support of a
      change to the timing of BCG administration to HIV-exposed neonates. METHODS: A
      case series of 17 HIV-infected patients with surgical complications of BCG
      vaccination. RESULTS: Seventeen patients are presented. The first two illustrate
      disseminated systemic BCG infection, resulting in BCG infection of the lymph
      nodes, liver, spleen and tibia, and the second with gastrointestinal involvement
      causing bowel obstruction. The other 15 patients represent a series of severe
      ulcerating lymphadenitis secondary to BCG. CONCLUSION: The risks of BCG in HIV
      infected infants are significant. Current recommendations are not satisfactory,
      and a change in policy is required to prevent the harmful effects of this vaccine
      in a high-risk group of patients. We believe that there is sufficient need to
      adequately stratify patients and vaccinate them according to a protocol that
      takes impaired immunity into consideration.

PMID- 19115759
TI  - Does examiner bias in undergraduate oral and clinical surgery examinations occur?
AB  - OBJECTIVE: Oral and long case clinical examinations are open to subjective
      influences to some extent, and students may be marked unfairly as a result of
      gender or racial bias or language problems. These concerns are of topical
      relevance in South Africa. The purpose of this study was to assess whether these
      factors influenced the marks given in these examinations. METHODS: Final-year
      surgery examination results from the University of Cape Town from 2003 to 2006
      were reviewed. These each consisted of a multiple choice paper, an objective
      structured clinical examination, a long case clinical examination and an oral
      examination. RESULTS: The marks of 604 students were analysed. Students who spoke
      English as a home language performed better in all examination modalities. Female
      students scored slightly higher than males overall, but they scored similarly in
      the clinical and oral examinations. There were significant differences in the
      marks scored between the various population groups in all examination modalities,
      with white students achieving the highest scores, and black students the lowest.
      These differences were most marked in multiple choice examinations, and least
      marked in oral and clinical examinations. CONCLUSION: We could find no evidence
      of systemic bias in the oral and clinical examinations in our department, which
      reinforces the need for ongoing academic support for students from disadvantaged
      educational backgrounds, and for those who do not speak English as a home
      language.

PMID- 19115760
TI  - Introduction: the twelve-step program model of AA.

PMID- 19115761
TI  - The twelve-step recovery model of AA: a voluntary mutual help association.
AB  - Alcoholism treatment has evolved to mean professionalized, scientifically based
      rehabilitation. Alcoholics Anonymous (AA) is not a treatment method; it is far
      better understood as a Twelve-Step Recovery Program within a voluntary self
      help/mutual aid organization of self-defined alcoholics. The Twelve-Step Recovery
      Model is elaborated in three sections, patterned on the AA logo (a triangle
      within a circle): The triangle's legs represent recovery, service, and unity; the
      circle represents the reinforcing effect of the three legs upon each other as
      well as the "technology" of the sharing circle and the fellowship. The first leg
      of the triangle, recovery, refers to the journey of individuals to abstinence and
      a new "way of living." The second leg, service, refers to helping other
      alcoholics which also connects the participants into a fellowship. The third leg,
      unity, refers to the fellowship of recovering alcoholics, their groups, and
      organizations. The distinctive AA organizational structure of an inverted pyramid
      is one in which the members in autonomous local groups direct input to the
      national service bodies creating a democratic, egalitarian organization
      maximizing recovery. Analysts describe the AA recovery program as complex,
      implicitly grounded in sound psychological principles, and more sophisticated
      than is typically understood. AA provides a nonmedicalized and anonymous "way of
      living" in the community and should probably be referred to as the Twelve
      Step/Twelve Tradition Recovery Model in order to clearly differentiate it from
      professionally based twelve-step treatments. There are additional self
      help/mutual aid groups for alcoholics who prefer philosophies other than AA.

PMID- 19115762
TI  - Twelve defining moments in the history of alcoholics anonymous.
AB  - Misconceptions about Alcoholics Anonymous (AA) abound in spite of (or because of)
      the thousands of theses, dissertations, books, professional and popular articles,
      and Internet commentaries that have been written about AA. One of the most
      pervasive characterizations of AA is that it is a "treatment" for alcoholism--a
      characterization that distorts the meaning of both mutual aid and alcoholism
      treatment. This article describes 12 character-defining moments in the history of
      AA that highlight the differences between AA and alcoholism treatment.

PMID- 19115763
TI  - The impact of AA on professional treatment.
AB  - Several forces combined in the 1950s to profoundly change the way alcoholism was
      treated in the United States. Anderson, Bradley, and Hazelden staff combined
      strategies to revolutionize alcoholism treatment across the spectrum of social
      rehabilitation services and hospital-based care. Prevailing psychiatric services,
      heavily influenced by psychoanalytic practices, were abandoned in favor of an
      emphasis on patient education, therapeutic group process, peer interaction, and
      the development of life-long support systems through AA. The addition of the
      alcoholism counselors, many of whom were recovering AA members, was a key
      ingredient in aligning a closely identified professional with the alcoholic to
      foster integration of Twelve Step principles and practices in everyday life.
      Dignity, respect, and hope for recovery became the cornerstone of the
      Minnesota/Hazelden Model. The resulting treatment model is recognized as an
      effective, evidence-based approach for alcohol and drug dependence. One of the
      strongest commendatory statements has come from the staff of the National
      Institute on Alcohol Abuse and Alcoholism who, in a report to the U.S. Congress,
      identified Twelve Step-based professional treatment as effective as other
      approaches and a model that "...may actually achieve more sustained abstinence"
      (2000, p. 448). Clearly, AA's impact on professional treatment cannot be
      underestimated. Perhaps Dan Anderson summarized it best: "Without the initial and
      sustaining impetus of [AA], none of our treatment efforts could have been
      realized" (Anderson, 1981, p. 3).

PMID- 19115764
TI  - The impact of alcoholics anonymous on other substance abuse-related twelve-step
      programs.
AB  - This chapter explores the influence of the AA model on self-help fellowships
      addressing problems of drug dependence. Fellowships that have adapted the twelve
      step recovery model to other substances of abuse are reviewed; next similarities
      and differences between AA and drug-recovery twelve-step organizations are
      examined; finally, we present empirical findings on patterns of attendance and
      perceptions of AA and Narcotics Anonymous (NA) among polydrug-dependent
      populations, many of whom are cross-addicted to alcohol. Future directions in
      twelve-step research are noted in closing.

PMID- 19115765
TI  - The impact of AA on non-professional substance abuse recovery programs and sober
      living houses.
AB  - In addition to being a widely used and effective approach for alcohol problems,
      AA has been central to the development of several types of nonprofessional
      recovery programs. Known as "social model recovery," these programs were staffed
      by individuals in recovery and they encouraged program participants to become
      involved in AA as a way to address their drinking problems. In addition, they
      relied on the traditions, beliefs, and recovery practices of AA as a guide for
      managing and operating programs (e.g., democratic group processes, shared and
      rotated leadership, and experiential knowledge). This chapter reviews the
      philosophy, history, and recent changes in several types of these programs, along
      with a depiction of AA's influence on them. Programs examined include
      neighborhood recovery centers, residential social model recovery programs, and
      two types of sober living houses: California Sober Living Houses and Oxford
      Houses. Recent outcome evaluations on both types of sober living houses are
      presented.

PMID- 19115766
TI  - An overview of spirituality in AA (and recovery).

PMID- 19115767
TI  - The concept of spirituality in relation to addiction recovery and general
      psychiatry.
AB  - This chapter is directed at defining the nature of spirituality and its
      relationship to empirical research and clinical practice. A preliminary
      understanding of the spiritual experience can be achieved on the basis of diverse
      theoretical and empirically grounded sources, which will be delineated: namely,
      physiology, psychology, and cross-cultural sources. Furthermore, the impact of
      spirituality on mental health and addiction in different cultural and clinical
      settings is explicated regarding both beneficial and compromising outcomes.
      Illustrations of its application in addiction and general psychiatry are given:
      in meditative practices, Alcoholics Anonymous, and treatment programs for
      addiction singly and comorbid with major mental illness. Given its prominence in
      Alcoholics Anonymous and related Twelve-Step groups, spirituality plays an
      important role in the rehabilitation of many substance-dependent people. The
      issue of spirituality, however, is prominent within contemporary culture as well
      in the form of theistic orientation, as evidenced in a probability sampling of
      American adults, among whom 95% of respondents reply positively when asked if
      they believe in "God or a universal spirit." Responses to a follow-up on this
      question suggest that this belief affects the daily lives of the majority (51%)
      of those sampled, as they indicated that they had talked to someone about God or
      some aspect of their faith or spirituality within the previous 24 h (Gallup,
      2002).

PMID- 19115768
TI  - Kickbacks from helping others: health and recovery.
AB  - AA is often viewed as a spiritual organization, but it is less commonly
      recognized that helping others is a fundamental part of AA's conception of
      spirituality. Helping others by bringing AA's program to other alcoholics
      (articulated in Step 12) is understood as the culmination of AA's program and the
      behavioral manifestation of a spiritual awakening (Step 11). Also, members are
      encouraged to help in all stages of their involvement in AA's, and it is this
      helping that is thought to keep them sober. Accordingly, the current chapter
      addresses the question of whether helping benefits the helper from an empirical
      standpoint-and specifically, whether helping might contribute to recovery in the
      context of AA involvement. In addition to describing AA's approach to helping, we
      review research on associations between helping and (a) health outcomes in the
      general population, (b) recovery in diverse mutual help groups, and (c) recovery
      from chemical dependency within and outside of AA. We find evidence supporting
      benefits for helpers in each of these domains and tentatively conclude in favor
      of helper therapy principles. However, the work is limited by the lack of
      experimental studies and by problems in defining helping. Other concerns are that
      "over-helping" can be worse than not helping at all and that helping may
      sometimes harm the intended recipients. Recommendations for further research are
      to address these limitations. Particularly useful would be research designing and
      testing interventions aiming to increase helping, perhaps informed by social
      model programs and principles.

PMID- 19115769
TI  - Issues in measuring spirituality and religiousness in alcohol research.

PMID- 19115770
TI  - Spirituality and health: empirically based reflections on recovery.
AB  - In this chapter, we explore the spiritual functioning and well-being of
      individuals and how this relates to mental health and recovery from alcoholism
      within the conceptual framework of Alcoholics Anonymous. We raise the question of
      whether the spiritually oriented focus of AA is a critical factor in achieving
      recovery. We suggest that examining the findings from a large body of research on
      religion and mental health may provide further insight into this question.
      Specifically, we assert that the mechanisms through which the spiritual focus of
      AA may influence recovery from alcoholism may be similar to the mechanisms
      through which spirituality may influence mental health. These potential
      explanatory mechanisms include the provision of a community, a narrative
      framework for meaning-making, a means of coping through submission and
      redemption, and prescribed lifestyle behaviors.

PMID- 19115771
TI  - Spiritual change in recovery.

PMID- 19115772
TI  - Mindfulness and addiction.

PMID- 19115773
TI  - Twelve-step membership. Introduction.

PMID- 19115774
TI  - Epidemiology of alcoholics anonymous participation.
AB  - This chapter draws on AA membership surveys, US general population surveys, and
      longitudinal treatment data to compile profiles of those ever exposed to AA in
      their lifetime, those who no longer report AA meeting attendance, and those who
      attend AA meetings currently. We consider demographics (gender, age, ethnicity,
      marital status), receipt of specialty treatment, and short- and long-term
      abstinence rates among these AA exposure groups. Results suggest stability in the
      representation of women and minorities among the AA membership, but a decline
      among youth. Fully one-half of those completing AA's most recent membership
      survey reported that they had been abstinent for more than 5 years. Those
      receiving specialty treatment any given year are likely to report AA exposure
      that year. Disengagement from AA does not appear to necessarily translate to loss
      of abstinence among those with initial high levels of AA exposure, but long-term
      abstinence is more likely among those with continued engagement.

PMID- 19115775
TI  - Concerns about dose and underutilization of twelve-step programs: models, scales,
      and theory that inform treatment planning.
AB  - Researchers have observed that a majority of addicted persons who are encouraged
      and facilitated by treatment providers to attend twelve-step (TS) programs either
      drop out or sporadically use twelve-step programs following treatment. This is
      troubling given considerable evidence of TS program benefits associated with
      regular weekly attendance and ubiquitous reliance by treatment professionals on
      these programs to provide important support services. This chapter reviews and
      advances theory of TS utilization and dose that is supported by prior research,
      multivariate models, and scales that predict risk of TS meeting underutilization.
      Advancing theory should organize and clarify the process of initial utilization,
      guide intervention development, and improve adherence of TS program referrals,
      all of which should lead to improved treatment planning and better outcomes.
      Three theories are integrated to explain processes that may influence TS program
      dose: the health belief model, self-determination theory (motivational theory),
      and a person-in-organization cultural fit theory. Four multidimensional scales
      developed specifically to predict participation are described. Implications for
      practice and future research are considered in a final discussion. Information
      contained in this chapter raises awareness of the need for TS-focused treatments
      to focus on achieving weekly attendance during and after treatment.

PMID- 19115776
TI  - Facilitating involvement in twelve-step programs.
AB  - Twelve-step programs represent a readily available resource for individuals with
      substance use disorders. These programs have demonstrated considerable
      effectiveness in helping substance abusers achieve and maintain abstinence and
      improve their overall psychosocial functioning and recovery. Despite these
      positive benefits associated with increased involvement in twelve-step self-help
      programs, many substance abusers do not affiliate or do so for only a short
      period of time before dropping out. Because of this, clinicians and researchers
      have sought ways to increase involvement in such self-help groups by facilitating
      meeting attendance and engagement in other twelve-step activities. The present
      chapter reviews the impact of treatment program orientation and specific
      interventions designed to facilitate twelve-step program involvement, subsequent
      meeting attendance, engagement in twelve-step activities, and alcohol and drug
      use. The findings of studies evaluating these approaches indicate that it is
      possible to increase twelve-step involvement and that doing so results in reduced
      substance use. The results suggest that incorporating these evidence-based
      interventions into standard treatment programs may lead to improved outcomes.

PMID- 19115777
TI  - Twelve-step facilitation in non-specialty settings.
AB  - Participation in the twelve-step mutual-help organization, Alcoholics Anonymous,
      has proven to be an effective means of helping individuals with alcohol
      dependence achieve lasting sobriety. Although many patients choose to attend AA
      of their own accord, clinicians' facilitation of AA involvement ("Twelve-Step
      Facilitation" [TSF]) has shown to substantially increase the likelihood that
      patients will become engaged with these freely available resources. Importantly,
      many individuals with alcohol dependence never seek help from addiction
      specialists, yet often encounter other health professionals due to alcohol
      related physical or psychological problems providing an opportunity for
      intervention. However, for clinicians who do not specialize in addiction
      treatment, knowledge about what AA actually is and does is often lacking, and
      confidence in implementing TSF strategies is low. This chapter provides essential
      information for clinicians working in non-specialty settings who have little
      knowledge of, or experience with, AA or TSF, but who may wish to utilize proven
      strategies to augment existing interventions by helping educate, link, and engage
      patients with AA. Detailed information on the origins and specific elements of AA
      is provided along with recommended TSF approaches and strategies to aid the non
      specialist in building effective interventions for patients with alcohol
      dependence.

PMID- 19115778
TI  - Effectiveness and outcome research. Introduction.

PMID- 19115779
TI  - Alcoholics anonymous outcomes and benefits.

PMID- 19115780
TI  - Outcomes of AA for special populations.

PMID- 19115781
TI  - How and why twelve-step self-help groups are effective.

PMID- 19115782
TI  - Individual and contextual factors that influence AA affiliation and outcomes.

PMID- 19115783
TI  - Patterns of fish community structure in a long-term watershed-scale study to
      address the aquatic ecosystem effects of pulp and paper mill discharges in four
      US receiving streams.
AB  - Physiological changes have been seen in individual fish exposed to pulp and paper
      mill effluent (PPME), but it is unclear whether community-level changes are seen
      in fish in PPME receiving waters. We conducted a study of 4 PPME receiving
      streams (Codorus Creek, PA, USA), the Leaf River (Forrest and Perry Counties, MS,
      USA), and the McKenzie and Willamette rivers (Lane County, OR, USA) over 9 y to
      assess temporal patterns in the type and relative abundance of fish species and
      measures of community structure and function related to PPME discharge. We used
      boat and backpack electrofishing to sample large- and small-bodied fish from the
      McKenzie and Willamette rivers, boat electrofishing to sample large-bodied fish
      from the Leaf River, and backpack electrofishing to sample the entire fish
      community from Codorus Creek. Study streams represented different ecoregions,
      warm- and coldwater systems, gradients of PPME concentration (<1%-33%), and mill
      process types. Bray-Curtis similarity and nonmetric multidimensional scaling
      showed high variation in fish communities across sites, seasons, and years.
      Significant site differences in fish communities were seen in most streams and
      community types, but distinct separation of sites was seen only in Codorus Creek
      and unrelated to PPME discharge. No seasonal differences were seen in fish
      community structure in any stream, with only weak annual patterns in large-bodied
      fish in the Leaf River and small-bodied fish in the McKenzie River. General
      linear models were used to examine spatial and temporal variation in fish metric
      response (abundance, species richness, Simpson's diversity, % dominant species,
      standing crop, % DELT, % intolerant, % omnivore, % piscivore). Significant site
      differences in metric response were largely limited to Codorus Creek and
      unrelated to PPME. Significant reductions of % dominant taxa of small-bodied fish
      and % large-bodied piscivores were also observed downstream of the PPME discharge
      on the McKenzie River relative to upstream sites. Seasonal changes in fish metric
      response were rare, and changes with year were variable. The relationship between
      fish community structure and water quality variables (pH, color, conductivity,
      total phosphorus, total nitrogen) was weak in all streams for all community
      types. The results of this study show that PPME exposure has little effect on
      fish communities in these streams and aid in addressing management strategies.
      The high spatial and temporal variability reiterate the importance of long-term
      studies to elucidate patterns in receiving waters.

PMID- 19115784
TI  - Metazoan parasite infracommunities of the toadfish Aphos porosus (Pisces:
      Batrachoidiformes) in central Chile: how variable are they over time?
AB  - The present study examines variation in parasite community characteristics of the
      toadfish Aphos porosus across sampling years. We analyzed and compared the
      species composition and numeric descriptors of the parasite infrapopulations and
      infracommunities in 101 fish collected during the springs of 1999, 2006, and 2007
      from rocky intertidal ponds in El Tabo, central Chile. Parasites were found in
      94.1% of specimens necropsied. In total 5,532 parasites were collected,
      representing 12 taxa, of which 7 were found in the 3 annual samples. The most
      prevalent and abundant parasites in the 3 sampling years were larval
      tetraphyllidean cestodes, followed by anisakid nematodes. The community
      descriptors of average richness and abundance varied significantly across the 3
      yr, with the exception of parasite dominance. The parasite species composition
      and relative abundance showed low variability among years. A few parasite taxa
      (Anisakis sp., Pseudoterranova sp., tetraphyllideans, and Clestobothrium
      crassiceps) dominated the infracommunities of the toadfish; however,
      tetraphyllideans were the parasites that greatly varied over time. Consequently
      the parasite infracommunities of the toadfish were variable among years, with a
      low variation in parasite composition, but large differences in the aggregate
      descriptors.

PMID- 19115785
TI  - Two new species of philometrids (Nematoda: Philometridae) from marine fishes off
      South Carolina.
AB  - Two new species of philometrid nematodes, Philometra gymnothoracis n. sp. and
      Philometroides marinus n. sp., are described from female specimens collected from
      the body cavity of the spotted moray, Gymnothorax moringa (Cuvier) (Muraenidae,
      Anguilliformes), and the cobia, Rachycentron canadum (Linnaeus) (Rachycentridae,
      Perciformes), respectively, from off the Atlantic coast of South Carolina.
      Philometra gymnothoracis n. sp. is mainly characterized by the conspicuously
      depressed mouth, the presence of 8 small cephalic papillae arranged in 4
      submedian pairs, the esophagus with an anterior bulbous inflation, 2 small
      papilla-like caudal projections, the body length of the gravid female 435-760 mm,
      short ovaries, the length of larvae from the uterus 474-544 microm, and by the
      location in the host (body cavity). Philometroides marinus n. sp. differs from
      its congeners parasitizing marine and brackish water fishes mainly in having
      small cuticular bosses only on the anterior part of the body; in possessing 4
      markedly large cephalic projections, each with 2 minute papillae, 2 large caudal
      projections, and in the location in the host (body cavity); the body length of
      subgravid and gravid females is 130-550 mm and that of larvae from the uterus 600
      642 microm.

PMID- 19115786
TI  - Severe snoring in a child with pycnodysostosis treated with a bilateral rib
      graft.
AB  - Pycnodysostosis is a rare osteopetrotic disorder. This report describes a case of
      a 3(1/2)-year-old boy with pycnodysostosis who presented with severe snoring. The
      snoring was the result of a pharyngeal narrowing due to a hypoplastic mandible.
      Surgery consisted of a bilateral rib graft, which allowed an enlargement of the
      pharynx by acting both on an anterior projection of the chin and a decrease of
      the glossoptosis. A significant reduction of the snoring and an excellent mouth
      aperture were obtained. This technique is ideal for such patients presenting a
      high risk of infection, nonunion, and secondary fracture.

PMID- 19115787
TI  - Cleft lip and/or palate with monogenic autosomal recessive transmission in
      Pyrenees shepherd dogs.
AB  - OBJECTIVE: To document the genetic background of Pyrenees shepherd dogs as it
      relates to the incidence of cleft lip and/or cleft palate, to describe the
      phenotype, and to determine possible candidate genes. DESIGN: Pedigree analysis
      was performed and blood samples were taken from five affected pups, their
      siblings, and parents. Seven candidate genes were selected and linkage analysis
      was performed. Further methods used included sequencing and histology. RESULTS:
      In 37 litters consisting of 163 pups, we found 47 affected pups in a total
      population of 2104. The male:female ratio was 1:0.96. Affected pups showed
      isolated cleft lip and/or cleft palate; no attendant disorders have been
      reported. Despite a high degree of relationship, two affected pups displayed a
      cleft palate (- H S H -) and a cleft lip with or without cleft palate (L A -)
      cleft formation. Histology of affected pups showed that the medial edge
      epithelium remained intact and did not undergo an epithelial-mesenchymal
      transformation. There was no evidence for linkage between the trait and TGFb3 or
      Msx1. Subsequent sequencing excluded the coding sequence of Fst as well.
      CONCLUSION: Pedigree analysis showed that cleft palate is not genetically
      distinct from cleft lip with or without cleft palate but is inherited in this
      breed as a monogenic autosomal recessive trait. Linkage analysis and sequencing
      excluded TGFb3, Msx1, and Fst as candidate genes. Histology of affected pups
      showed that the medial edge epithelium is still intact.

PMID- 19115788
TI  - Abnormalities of maxillary anterior teeth in Chinese children with cleft lip and
      palate.
AB  - OBJECTIVE: To retrospectively study the anterior maxilla of southern Chinese
      children with complete cleft lip and palate (CLP) for the prevalence of different
      kinds of dental anomalies, position and rotation of the teeth, and the asymmetry
      of dental development. PATIENTS: 195 southern Chinese children with CLP aged
      between 3 and 17 years. METHODS AND MATERIALS: Dental records and study casts
      were studied as were the radiographs from which the dental development was
      determined. RESULTS: The tooth prevalence of cleft side permanent lateral incisor
      was 19.2% in unilateral CLP (UCLP) children and 20.5% in bilateral CLP (BCLP)
      children. The cleft side central incisors were rotated in 78.1% and 95.9% of the
      teeth in UCLP and BCLP children, respectively. Of the permanent canines, 43.4%
      were positioned mesially on the cleft side in UCLP children, while for BCLP
      children 69.7% of the teeth were in a normal position. In addition, the mesially
      positioned canines were often associated with an absence of the permanent lateral
      incisor while the distally positioned canines were always associated with the
      presence of supernumeraries in the cleft region. The permanent teeth on the cleft
      side showed significantly delayed development compared with their antimeres on
      the noncleft side; however, the delayed permanent lateral incisors did complete
      their formation normally. CONCLUSION: This group of Chinese children with CLP
      demonstrated statistically significant higher prevalences of hypodontia,
      microdontia, and delayed dental development on the cleft side than the noncleft
      side.

PMID- 19115789
TI  - A preoperative appliance for a newborn with cleft palate.
AB  - Cleft palate is a commonly observed congenital maxillofacial defect. One of the
      most important problems with clefts is the interference with feeding. An affected
      infant cannot produce negative pressure in the oral cavity and therefore cannot
      move the bolus backward to the pharynx. To obtain better nutritional intake prior
      to surgical correction, a palatal lift obturator is recommended. In this clinical
      report, a modified technique of obturator fabrication is presented. The new
      method uses a piece of tulle, a flexible and durable material that is frequently
      used in theater attire. With the help of this material, the bulb part is
      connected to the plate as a labile piece, and this connection acts like a natural
      velopharyngeal extension. Additionally, because of the softer property of the
      silicone elastomer, the posterior pharyngeal wall is less irritated.

PMID- 19115790
TI  - Temporary tongue-lip traction during the initial period of mandibular distraction
      in Pierre Robin sequence.
AB  - OBJECTIVE: Distraction osteogenesis is a good technique to correct micrognathia
      and to prevent tracheostomy in patients with Pierre Robin sequence. However, the
      airway must be maintained during the distraction period. The purpose of this
      study was to determine the usefulness of temporary tongue-lip traction during the
      initial period of mandibular distraction in Pierre Robin sequence patients with
      severe airway problems requiring operative procedures. PATIENTS: Three Pierre
      Robin sequence patients between 4 months and 3 years of age requiring surgical
      procedures to correct recurrent and severe pulmonary complications. METHOD: All
      patients underwent distraction osteogenesis of the mandible. During surgery, a
      deep one-tension suture was used to apply traction to the tongue. When the
      patient gained control of the upper airway during the initial period of
      distraction and micrognathia was corrected, the traction suture was removed.
      RESULTS: The patients were followed for a mean of 5.4 years. No patients
      complained of severe pulmonary complications, and tracheostomy was avoided. The
      lower face area was increased in all three patients. CONCLUSION: In severe Pierre
      Robin sequence cases, temporary tongue-lip traction was a good adjunct to
      distraction osteogenesis because this method avoided tracheostomy.

PMID- 19115791
TI  - Effects of altered fundamental frequency on nasalance during vowel production by
      adult speakers at targeted sound pressure levels.
AB  - OBJECTIVE: This study investigated the effects of altered fundamental frequency
      (F0) on nasalance levels of the vowels /i/ and /a/ produced by adults without
      cleft palate within a controlled sound pressure level (SPL) range. DESIGN: A
      prospective group design with convenience sampling from the University of North
      Carolina at Chapel Hill was used. PARTICIPANTS: 20 men and 20 women participated,
      aged 18 to 55 years. All were native English speakers with normal speech and
      language skills and adequate velopharyngeal function. MAIN OUTCOME MEASURES: The
      outcome measures were percentage nasalance obtained from the Nasometer 6200
      (KayPentax) headset and the Computerized Speech Lab Model 4400 (CSL, KayPentax)
      during vowel production while speakers (1) targeted an SPL range of 75 to 85 dB
      and (2) targeted the SPL plus F0 range of 165 to 175 Hz. RESULTS: A significant
      univariate effect was found for the vowels /i/ and /a/ in the targeted SPL
      condition such that /i/ was produced with higher nasalance than /a/. A
      significant univariate effect was also found during production of /a/ in the
      targeted SPL plus F0 condition such that men produced /a/ with higher nasalance
      than women did. CONCLUSIONS: SPL appears to largely account for percentage
      nasalance differences between the vowels /i/ and /a/ produced by adult male and
      female speakers. Increased F0 by male speakers appears to influence percentage
      nasalance during production of the vowel /a/. Clinical implications in regard to
      assessment of hypernasality are discussed.

PMID- 19115792
TI  - Social experience in 10-year-old children born with a cleft: exploring
      psychosocial resilience.
AB  - OBJECTIVE: The purposes of this study were to investigate self-reported social
      experience in 10-year-old children born with a cleft lip and/or palate and to
      gain a better understanding of variables implicated in psychosocial resilience.
      DESIGN: Cross-sectional study of 10-year-old children from five consecutive birth
      cohorts, born from 1992 to 1997. PARTICIPANTS: A total of 268 children treated by
      the Oslo cleft team (Norway) participated in the study. The children's cleft
      conditions included cleft lip and palate, cleft lip alveolus, cleft palate, and
      submucous cleft palate. OUTCOME MEASURES: Psychosocial resilience was measured
      with the Child Experience Questionnaire (CEQ). Other variables were obtained
      during a clinical interview with the child. Cognitive, emotional, and
      psychosocial functioning was measured with the Personality Inventory for Children
      (PIC). Satisfaction with appearance was assessed through the use of the
      Satisfaction with Appearance Scales (SWA). Informants were both children and
      parents. RESULTS: Cleft types differed significantly with respect to subtype and
      frequency of additional difficulties. Psychosocial resilience was associated with
      adequate emotional functioning, high satisfaction with appearance, and a lower
      frequency of reported teasing. Child characteristics such as visibility of cleft,
      gender, and additional diagnosis did not contribute to explain psychosocial
      resilience. CONCLUSIONS: Results reported here emphasise the importance of
      assessing the child's subjective report of satisfaction with appearance and
      psychosocial experience.

PMID- 19115793
TI  - Association analysis between the IRF6 G820A polymorphism and nonsyndromic cleft
      lip and/or cleft palate in a Chinese population.
AB  - OBJECTIVE: To investigate whether an association occurred between the IRF6 G820A
      polymorphism and nonsyndromic cleft lip with or without cleft palate (CL+/-P) or
      cleft palate only (CPO) in Chinese patients. DESIGN AND SETTING: Case-controlled
      study at the West China Hospital of Stomatology, Sichuan University, China.
      SUBJECTS: A total of 91 patients with cleft lip and/or palate (CL/P) and 96
      unrelated, healthy individuals with no family history of CL/P were genotyped.
      METHODS: The IRF6 G820A polymorphism was genotyped by restriction digestion of
      polymerase chain reaction products with BseLI. Chi-square statistics were used to
      make case-controlled comparisons. RESULTS: The frequency of the A allele was
      significantly increased and the frequency of the G allele was reduced in CPO
      patients in comparison with control subjects. The 820GG genotype had a
      significantly lower frequency in patients with CPO than in controls, with an odds
      ratio of 0.25 (95% confidence interval, -0.061 to 0.57). No difference in the
      distribution of genotypes was noted between CL+/-P patients and the total group
      of CL/P patients compared with controls. CONCLUSIONS: The present findings
      indicate that the 820A allele is more frequent in the Chinese CPO population and
      may confer an increased risk for CPO in these individuals. The G820A variant may
      be in linkage disequilibrium with other disorder-causing mutations. CL+/-P or CPO
      results should be analyzed separately and stratified in future studies.

PMID- 19115794
TI  - The natural history of audiologic and tympanometric findings in patients with an
      unrepaired cleft palate.
AB  - OBJECTIVE: To present the tympanometric findings in 552 patients (115 over 10
      years of age) with unrepaired cleft palate (256 had audiologic findings) and to
      show the natural history and outcome of these cases. SETTING: The cleft lip and
      palate clinic for the Division of Cleft Lip and Palate Surgery at the West China
      College of Stomatology, Sichuan University, Chengdu, People's Republic of China.
      DESIGN: Pure-tone audiometric and tympanometric evaluations were performed on 552
      patients with an unrepaired cleft palate. Results were analyzed by looking at the
      patient's age and cleft palate type. RESULTS: This study demonstrated an age
      related decrease in the frequency of hearing impairment and abnormal
      tympanometry. The frequency of hearing impairment and abnormal tympanometry in
      patients with submucous cleft palate was significantly lower than in patients
      from the other four major cleft palate categories (p = .001, p = .006,
      respectively). CONCLUSIONS: The middle ear function and hearing levels of
      unrepaired cleft palate patients improved with age, but at least 30% of the
      patients' ears demonstrated a hearing loss and abnormal tympanometry in each age
      group, including those over 19 years of age. In the crucial language-learning
      stage, the frequency of hearing impairment and abnormal tympanometry was as high
      as 60%. Considering these results, palate repair and surgical intervention, such
      as tube insertion, for otological problems should be considered at an early age.

PMID- 19115795
TI  - Unblocking the nose by unplugging the ear: the use of foam ear defenders as a
      splint following secondary cleft rhinoplasty.
AB  - OBJECTIVE: The functional and aesthetic result from secondary cleft rhinoplasty
      is commonly impaired by a bulge in the lateral nasal vestibule, which can relapse
      in the postoperative period despite careful intraoperative correction. We aim to
      improve our results by using a foam ear defender as a postoperative splint to
      prevent relapse. DESIGN: Case series of 10 patients with photographs of a typical
      clinical case. INTERVENTIONS: The postoperative nasal pack was exchanged with a
      foam ear defender on day 5. The splint was worn continuously for 3 to 4 weeks,
      then nightly for 3 months. The splint was changed daily by the patient. MAIN
      OUTCOME MEASURES: The results were assessed clinically by the senior author.
      RESULTS: The patients had little or no recurrence of the lateral vestibular bulge
      following nasal splintage. CONCLUSIONS: Foam ear defenders are a simple, cheap,
      and comfortable method to provide splintage to the nasal vestibule following
      secondary cleft rhinoplasty.

PMID- 19115796
TI  - Alveolar bone grafting for patients with unilateral complete alveolar and palatal
      clefts improves the bony structure of the nose.
AB  - OBJECTIVE: This is a retrospective study regarding the effect of alveolar bone
      grafting (ABG) on morphological changes in the bony structure of the nose in
      alveolar and palatal cleft patients. METHODS: Sixty-five randomly selected adults
      were included in the present study. Of the 65 subjects, 21 had no congenital
      anomaly and were designated as the control group (n = 21; mean age 22.4 +/- 4.3
      years). Forty-four had unilateral complete clefts of the alveolus and palate on
      the left side. The patients with clefts were further divided into two subgroups
      based on presence or absence of ABG in their histories. These groups were termed
      the ABG(+) group (n = 24; mean age 20.3 +/- 2.5 years) and the ABG(-) group (n =
      20; mean age 32 +/- 4.5 years), respectively. An anatomical structure that
      constitutes the bony component of the nose was defined. This structure, composed
      of the nasal bones and part of the frontal process of the maxilla, was termed the
      BSEN (bony structure of the external nose). The symmetry of the BSEN was assessed
      quantitatively by performing morphological measurements on computerized
      tomographic images of each patient's skull, and these measurements were compared
      among the control, ABG(+), and ABG(-) groups. RESULTS: The BSEN presented more
      symmetric features in the ABG(+) group patients than in the ABG(-) group
      patients. CONCLUSION: ABG improves symmetry of the BSEN. This finding justifies
      ABG in terms of cosmetic improvement of the external nose in patients with
      unilateral complete alveolar and palatal clefts.

PMID- 19115797
TI  - Evaluation of hypernasality in vowels using voice low tone to high tone ratio.
AB  - OBJECTIVE: The voice low tone to high tone ratio (VLHR) is defined as the power
      ratio of low frequency to high frequency energy obtained by dividing the voice
      spectrum with a specific cutoff frequency. In a previous study, VLHR correlated
      significantly with nasalance and perceptual rating of hypernasality for a single
      vowel. The methodology was optimized in this study by investigating the
      correlations among other vowels. DESIGN: Voice signals of six sustained vowels
      vocalized by subjects with hypernasality were collected. Vowel nasalance was
      obtained with a nasometer, and hypernasality rating scores were provided by two
      speech-language pathologists. The VLHRs calculated using different cutoff
      frequencies were correlated with nasalance and hypernasality rating scores.
      PARTICIPANTS: Eight subjects with hypernasality caused by palatal fistula or
      velopharyngeal insufficiency. MAIN OUTCOME MEASURES: VLHR, nasalance, and
      hypernasality rating score. RESULTS: The correlation of VLHR with nasalance and
      hypernasality rating was most significant using a cutoff frequency of 600 Hz. The
      correlation of VLHR with nasalance was significant (r = .62, p < .01, Pearson's
      correlation), as was the correlation of VLHR with hypernasality score (Spearman's
      rank correlation coefficient = .62, p < .01). CONCLUSIONS: VLHR correlated
      significantly with nasalance and hypernasality in the six sustained vowels and
      may provide another quantitative index for the evaluation of hypernasality in
      sustained vowels.

PMID- 19115798
TI  - Internet-derived information on cleft lip and palate for families with affected
      children.
AB  - OBJECTIVE: To investigate the nature and readability of cleft lip and palate
      related family information on the Internet. MATERIALS AND METHODS: An Internet
      search for "cleft lip," "cleft palate," and "family information" was carried out
      using three search engines. Within each search, the first 25 relevant websites
      identified were downloaded and assessed for country of origin, authorship,
      domain, referencing, links, advertising, mention of orthodontics, illustrations,
      cleft-specificity, and content. Readability was determined using the Flesch
      Reading Ease Score, the Flesch-Kincaid Grade Level, and the Fog Scale Level. Data
      were analyzed by simple descriptive statistics. RESULTS: The initial search
      returned in excess of 1,800,000 hits. A total of 49 websites were evaluated,
      excluding repetitions, with a wide range of information available. The websites
      assessed were mostly of U.S. origin, with a .org domain, authored by
      universities/hospitals, not cleft-specific, without advertisements, contained
      links but not references, mentioned orthodontics even if to a small extent,
      contained some form of illustrations, and varied greatly in quantity and quality
      of information presented. A wide range of readability scores was obtained,
      equating to reading ages from fourth grade to university graduate level, with a
      mean reading age at the eighth to ninth grade level. CONCLUSIONS: Cleft lip and
      palate-related information for families on the Internet is variable in content,
      quality, and readability. Clinicians should have the responsibility to guide and
      help parents with website retrieval, while authors of websites should aim to keep
      information readable and relevant to family demands.

PMID- 19115799
TI  - Rehabilitation of an edentulous cleft lip and palate patient with a soft palate
      defect using a bar-retained, implant-supported speech-aid prosthesis: a clinical
      report.
AB  - Prosthetic rehabilitation of an edentulous cleft lip and palate patient with a
      combined hard and soft palate defect is a great challenge, due to the lack of
      retention of the obturator prosthesis as a result of its weight and the inability
      to obtain a border seal. Dental implants improve the retention, stability, and
      occlusal function of prostheses when used in carefully selected cleft lip and
      palate cases. This clinical report presents an edentulous unilateral cleft lip
      and palate patient who has hard and soft palate defects and an atrophied maxilla,
      treated with an implant-supported speech-aid prosthesis.

PMID- 19115800
TI  - The management of otitis media with early routine insertion of grommets in
      children with cleft palate -- a systematic review.
AB  - OBJECTIVE: To determine whether early routine grommet insertion in children with
      cleft palate has a beneficial effect on hearing and speech and language
      development compared with conservative management. DESIGN: Systematic review of
      randomized controlled trials, controlled clinical trials, case series, and
      prospective and historical cohort studies. MAIN OUTCOME MEASURES: The main
      outcome measure was the effect of early routine grommet placement on the degree
      of conductive hearing loss. Secondary outcome measures included differences in
      hearing level, possible side effects, speech and language development, and
      quality of life. RESULTS: We identified 368 citations for review. From a review
      of the titles, 34 potentially relevant papers were selected. Of these, 18 studies
      met our inclusion criteria, including eight case series, six historical cohort
      studies, three prospective cohort studies, and one randomized trial. Most studies
      were either small or of poor quality or both. The results of the studies were
      contradictory, with some studies suggesting early placement of grommets was
      beneficial and others reporting there was no benefit. CONCLUSIONS: There is
      currently insufficient evidence on which to base the clinical practice of early
      routine grommet placement in children with cleft palate.

PMID- 19115801
TI  - Advanced s(t)imulator for cleft palate repair techniques.
AB  - OBJECTIVE: Our aim was to create a simple, inexpensive, reproducible, and life
      size model of the oral cavity of a cleft palate patient. A step-by-step
      description of the assembly of our cleft palate simulator and its usefulness is
      presented. MATERIALS: This model was made with readily available components, such
      as alginate impression material, impression plaster, paper template, latex
      examination gloves, ink pad, disposable water cup, rubber dam, rubber band, and
      water-based and fast-setting glue. RESULT: Repeated trials showed that the model
      can be assembled in a fast and straightforward way. The model was appropriate for
      simulating the structure of a cleft palate, and the Furlow double-opposing Z
      plasty could be readily performed on this model. CONCLUSION: Our cleft palate
      simulator enables both the novice and keen cleft surgeons to simulate the
      intraoral situation of a cleft palate patient and to stimulate them to practice
      surgical techniques of palatal repair.

PMID- 19115802
TI  - Prosthetic rehabilitation of segmental odontomaxillary dysplasia: seven-year
      follow-up.
AB  - Segmental odontomaxillary dysplasia is an uncommon maxillofacial deformity.
      Clinically, overgrowth and maturation of the maxillary right or left posterior
      alveolus and the respective gingiva, lack of premolars, delayed eruption of the
      adjacent teeth, and malformed primary molars are observed. The purpose of this
      report was to describe the clinical and radiographic findings of a 47-year-old
      female with segmental odontomaxillary dysplasia and summarize the prosthetic
      rehabilitation with fixed and removable partial dentures. A 7-year follow-up did
      not reveal biomechanical or functional problems except the loss of the mandibular
      left central incisor and wear of the artificial teeth.

PMID- 19115805
TI  - A long-term, multitrophic level study to assess pulp and paper mill effluent
      effects on aquatic communities in four US receiving waters: lessons learned.
AB  - Lessons learned from the development, implementation, and initial 8 y of study
      findings from a long-term study to assess the effects of pulp and paper mill
      effluents on receiving waters are summarized as a conclusion to a series of
      articles (this issue) on study findings. The study, based on industry-defined
      information needs, was developed via a science-based experimental design into a
      long-term (>10 y) watershed-scale monitoring program that integrated in-stream
      population/ community assessment, laboratory chronic bioassays, and fathead
      minnow full life-cycle assays as well as water quality and effluent quality
      monitoring and habitat assessment in addressing the presence of effluent effects.
      The 4 study streams (Codorus Creek, PA; Leaf River, MS; and the McKenzie and
      Willamette rivers, OR) represented both bleached and unbleached kraft mill
      processes and effluent concentrations that ranged from near typical for the
      United States (0.4%) to very high (Codorus Creek= 32%). Following 8 y of
      monitoring, the weight of evidence suggests an absence of biological differences
      at stations downstream of the mill discharges for periphyton or
      macroinvertebrates and, with the exception of 1 of 9 large-bodied fish and 1 of 7
      small-bodied fish community structure metrics for 1 river (McKenzie), an absence
      of differences for fish communities. Laboratory bioassay and fathead minnow full
      life cycle tests supported a substantial "margin of safety" in that, depending on
      the effluent, adverse responses did not occur until effluent concentrations were
      from 2 times to more than 150 times in-stream concentrations. The incorporation
      of a watershed spatial scale illustrated that each sample site tended to be
      unique over the 28 to 50 km monitored segments with respect to habitat and that
      knowledge of these variables permitted accurate evaluations of effluent effects.
      Similarly, the multiyear study framework provided information regarding the
      natural seasonal and year-to-year variability in fish communities and
      consequently a better understanding of how potential effluent effects signals
      could be expressed within this variability. The study incorporated an adaptive
      management strategy that provided for study design and monitoring modifications
      over time as a way of benefiting from practical experience and knowledge gained
      through time and to optimize the use of study resources. Results from this
      initial 8 y of monitoring, to our knowledge, represent the longest-known
      population/community-level assessment of the in-stream effects of pulp and paper
      mill effluents. Beyond the lessons learned with respect to effluent effects are
      those related to the esign and conduct of long-term watershed-scale studies that
      may be of use to others in developing watershed assessment or management
      programs.

PMID- 19115806
TI  - Lead in Sarbaz River Basin sediments, Sistan and Baluchestan, Iran.
AB  - Streambed-sediment samples were collected in the Sarbaz River Basin in Sistan and
      Baluchestan Province, east of Iran, to characterize the occurrence and
      distribution of lead in natural and anthropogenic sites of the basin. During June
      and July 2008, stream sediment was collected at 30 sites, and the samples were
      analyzed for lead. Sites sampled represented agricultural, mining, mixed,
      rangeland, recreation, and residential land uses and background conditions. Lead
      was detected in all collected stream-sediment samples of the basin. Most of the
      lead concentration was associated with the smaller part of the 2 grain-size
      fractions: 2000 to 43 microm and <43 microm. The range in concentrations of lead
      at urban/rural sites generally was higher than the range of concentrations at
      nonurban/rural sites. Sediment from 2 distinctly different rock types in urban/
      rural areas were not significantly different (t = 0.1330, p = 0.8955) for
      concentrations of lead. Concentrations of lead were not significantly different
      (t = 0.0845, p = 0.6865) between main-stem sites and tributary sites.
      Concentrations of lead exceeded established sediment-quality guidelines for
      adverse effects on aquatic biota at most of the urban/rural sites in the study
      area.

PMID- 19115808
TI  - Stereoselective formation of alkenyl halides via magnesium halide promoted ring
      opening of bis-activated cyclopropenes.
AB  - In the presence of stoichiometric magnesium halides, a range of bis-activated
      cyclopropenes undergo highly stereoselective ring-opening reactions to produce
      multisubstituted alkenyl halides. More highly functionalized compounds may be
      obtained by trapping of the magnesium enolate intermediates in situ.

PMID- 19115807
TI  - Assessing surface area evolution during biomimetic growth of hydroxyapatite
      coatings.
AB  - The surface area of biomimetically deposited hydroxyapatite (HA) coatings on
      metallic implants is important for the biological performance of the implant.
      Thus, a nondestructive method of assessing this quantity directly on the solid
      substrate would be highly valuable. The objective of this study was to develop
      such a method and for the first time assess the evolution of surface area of HA
      during biomimetic growth. The surface area of a TiO2-covered titanium substrate
      was measured prior to and following the biomimetic coating deposition using Ar
      gas adsorption at 77 K. The presence of HA on the surface was verified with
      scanning electron microscopy and X-ray diffraction. The specific surface area of
      the coating was found to increase linearly during 1 week of deposition at a rate
      of approximately 100 cm2 day-1 (g substrate)-1. The presented method may be used
      as a tool for studying the evolution in surface area of coatings on solid
      substrates during biomimetic deposition or other growth processes.

PMID- 19115809
TI  - Simulation study of the correlation between structure and conductivity in
      stretched nafion.
AB  - We have used coarse-grained simulation methods to investigate the effect of
      stretching-induced structure orientation on the proton conductivity of Nafion
      like polymer electrolyte membranes. Our simulations show that uniaxial stretching
      causes the hydrophilic regions to become elongated in the stretching direction.
      This change has a strong effect on the proton conductivity, which is enhanced
      along the stretching direction, while the conductivity perpendicular to the
      stretched polymer backbone is reduced. In a humidified membrane, stretching also
      causes the perfluorinated side chains to tend to orient perpendicular to the
      stretching axis. This in turn affects the distribution of water at low water
      contents. The water forms a continuous network with narrow bridges between small
      water clusters absorbed in head group multiplets. In a dry membrane the side
      chains orient along the stretching direction.

PMID- 19115810
TI  - Total synthesis of (-)-5,6-dihydrocineromycin B.
AB  - An asymmetric total synthesis of (-)-5,6-dihydrocineromycin B has been
      accomplished in 13 steps from (-)-linalool O-triethylsilyl ether or 12 steps from
      geraniol. The present synthesis features (i) an intermolecular Wittig reaction
      involving an aldehyde possessing a ketophosphonate functionality and (ii) an
      intramolecular Horner-Wadsworth-Emmons olefination.

PMID- 19115811
TI  - Diversity of solvent dependent energy transfer pathways in heme proteins.
AB  - The time scales and pathways of heme cooling in both reduced cytochrome c and
      oxidized cytochrome c following heme photoexcitation were studied using molecular
      dynamics simulation. Five different solvent models, including normal water, heavy
      water, normal glycerol, deuterated glycerol, and a nonpolar solvent, were used in
      the simulation. Single exponential decay of the excess kinetic energy of the heme
      following photoexcitation was observed in all systems studied. The simulated time
      scale for heme cooling in normal water agrees with recent experimental results.
      In contrast to heme cooling in myoglobin, no solvent dependence was observed for
      the time scale for heme cooling in cytochrome c. The diversity of solvent
      dependence results from the different local heme environments in the two
      proteins. In myoglobin, it has been established that the dominant mechanism for
      heme cooling is direct energy transfer from the heme to the solvent. In
      cytochrome c, direct interaction between heme and protein residues forms the
      dominant energy transfer pathway. This distinction is dictated by protein
      topology and linked to function.

PMID- 19115812
TI  - Force field for molecular dynamics studies of glycine/water mixtures in
      crystal/solution environments.
AB  - Defining a force field for the theoretical predictions of the structure and
      growth of pharmaceutical crystals is very difficult because of the complex
      intermolecular bonding found in these crystals. Here, we investigate the accuracy
      of the AMBER ff03 force field for alpha-glycine molecules using molecular
      dynamics. The validation of the force field is carried out in both solution and
      crystal/solution environments. The molecule alpha-glycine is chosen because it
      has a simple molecular structure while displaying complex intermolecular
      interactions typical of pharmaceutical crystals. We estimate the atomic charge
      for glycine from density-functional theory and represent water by the extended
      simple point charge (SPC/E) model. In a pure solution environment, our simulation
      results agree well with the experimental data available for solution density,
      radial distribution functions, hydration number, and diffusion coefficient of
      glycine. In the crystal/solution environment, the lattice energy calculations are
      in agreement with the available literature results and also the force field is
      able to identify the hydrophilic nature of the (010) surface of glycine crystal.
      The good agreement between simulation results and experimental data indicates
      that the chosen force field can be used to investigate the growth of glycine
      crystals from aqueous solutions.

PMID- 19115813
TI  - Photochemistry of 7-hydroxy-2-(4-hydroxystyryl)-1-benzopyrylium and related
      compounds.
AB  - 2-Styryl-1-benzopyrylium derivatives exhibit deeper hues and absorption spectra
      that are substantially red-shifted when compared with their 2-phenyl-1
      benzopyrylium analogues. They follow the same pH and light-dependent network of
      chemical reactions previously described for 2-phenyl-1-benzopyrylium compounds.
      In this work, the photochromic properties of 7-hydroxy-2-(4-hydroxystyryl)-1
      benzopyrylium chloride are reported. This compound was fully characterized by UV
      vis absorption, fluorescence emission, pH jumps, and flash photolysis, and its
      properties were compared with the analogue 7,4'-dihydroxyflavylium (7-hydroxy-2
      (4-hydroxyphenyl)-1-benzopyrylium). The trans-chalcones of both compounds lacking
      the hydroxyl in position 2 were synthesized and used as model compounds since
      they exhibit cis-trans isomerization but cannot be involved in the other
      processes resulting from the ring closure. The transient absorption of two
      triplets attributed to the chalcones Ct/Ct(-), and a tautomer was detected by
      nanosecond flash photolysis, independent of the existence of the 2-hydroxyl
      substituent. The experimental results are compatible with the main formation of
      cis-chalcone from the singlet state. In the case of the styryl derivatives, the
      fraction of triplet formed from excitation of Ct is much higher, and the fraction
      of isomerization is much smaller. For this reason, the photochemistry of 7
      hydroxy-2-(4-hydroxystyryl)-1-benzopyrylium in water is much less efficient than
      that of its parent 7,4'-dihydroxyflavylium; however, in the presence of CTAB
      micelles, intense red colors can be obtained upon irradiation, confirming the
      usefulness of this family of compounds as photochromic systems.

PMID- 19115814
TI  - Unusual temperature dependence of photosynthetic electron transfer due to protein
      dynamics.
AB  - The initial electron transfer rate and protein dynamics in wild type and five
      mutant reaction centers from Rhodobacter sphaeroides have been studied as a
      function of temperature (10-295 K). Detailed kinetic measurements of initial
      electron transfer in Rhodobacter sphaeroides reaction centers can be
      quantitatively described by a reaction diffusion formalism at all temperatures
      from 10 to 295 K. In this model, the time course of electron transfer is
      determined by the ability of the protein to interconvert between conformations
      until one is found where the activation energy for electron transfer is near
      zero. In reaction centers with a free energy for electron transfer similar to
      wild type, the reaction proceeds at least as fast at cryogenic temperatures as at
      room temperature. This may be because interconversion between conformations at
      low temperature is restricted to conformations with near zero activation energy
      (it is not possible to diffuse away from this region of conformational space). In
      contrast, mutants with a decreased free energy initially find themselves in
      conformations unfavorable for electron transfer and require more extensive
      conformational diffusion to achieve a low activation energy conformation. They
      therefore undergo electron transfer more slowly at 10 K vs 295 K.

PMID- 19115815
TI  - Intercalation of aggregation-free and well-dispersed gold nanoparticles into the
      walls of mesoporous silica as a robust "green" catalyst for n-alkane oxidation.
AB  - Aggregate-free and well-dispersed gold nanoparticles were intercalated into the
      walls of mesoporous silica forming a nanoreactor demonstrating high catalytic
      activity for "green" alkane oxidation. The material is robust and can be
      recycled. The method may be developed to intercalate other metal or alloy
      nanoparticles into the walls of mesoporous silica.

PMID- 19115816
TI  - 6-Methoxy-N-alkyl isatin acylhydrazone derivatives as a novel series of potent
      selective cannabinoid receptor 2 inverse agonists: design, synthesis, and binding
      mode prediction.
AB  - Recently, we discovered and reported a series of N-alkyl isatin acylhydrazone
      derivatives that are potent CB2 agonists. Here, we describe a novel series of
      selective CB2 inverse agonists resulting from introduction of a methoxy moiety in
      position 6 of the isatin scaffold. These novel 6-methoxy-N-alkyl isatin
      acylhydrazone derivatives exhibited high CB2 functional activity and selectivity
      at human CB2. Compound 16 (MDA77) had high activity (EC(50) = 5.82 nM) at CB2 and
      no activity at CB1. Compound 15 (MDA55) (K(i) = 89.9 nM, EC(50) = 88.2 nM at CB2)
      inhibited the effect of compound 1 (MDA7), a selective CB2 agonist, in an animal
      model of neuropathic pain. The molecular modeling study presented here represents
      a first study of CB2 based on the structure of beta(2)-adrenergic receptor. A
      ligand-based homology model of the CB2 binding site was developed, and on the
      basis of our results, we propose a general binding mode for this class of inverse
      agonists with CB2.

PMID- 19115817
TI  - Fluorescence behavior of a pyrene-end-capped poly(ethylene oxide) in organic
      solvents and in dioxane-water mixtures.
AB  - A poly(ethylene oxide) polymer end-labeled with two pyrene units (M(w) = 9500
      g/mol and abbreviated as Py(2)PEO) was investigated in dioxane-water mixtures and
      several organic solvents by steady-state and time-resolved fluorescence
      techniques. In dioxane-water mixtures, the fluorescence emission spectra indicate
      that with the gradual addition of dioxane to the solvent mixture, the maximum of
      the pyrene monomer band remains practically constant, whereas the excimer band
      displays a blue shift of approximately 8-10 nm. From time-resolved fluorescence
      data, two- and three-exponential decays at the pyrene monomer and excimer
      emission wavelengths, respectively, were obtained. Two of the decay times (tau(1)
      and tau(2)) are identical at all emission wavelengths. The additional shorter
      decay time (tau(3)), which is only observed at the excimer emission wavelength,
      was attributed to the component responsible for the blue-shifted excimer maximum,
      that is, to a second excimer, uncoupled to the other two species. Thus, the time
      resolved fluorescence data suggests that one pyrene monomer is able to form
      either one or two excimers (E(1) and E(2), coupled and uncoupled, respectively).
      The sum of the pre-exponential factors, associated with the coupled species, at
      the excimer emission wavelength in dioxane-water mixtures always differs from
      zero. This, together with differences in the excitation spectra when collected at
      the monomer and excimer wavelengths, revealed that a static route is partially
      responsible for E(1)* formation. In the case of pure organic solvents, the
      proposed kinetic scheme can be simplified. In this case, the sum of the pre
      exponential factors at the excimer emission wavelength is practically zero, which
      is a direct consequence of the dynamic mechanism being the only route for E(1)*
      formation. The kinetic scheme has been solved, and the rate constants for excimer
      formation (k(a)), dissociation (k(d)), and excimer decay (k(E)) are presented.

PMID- 19115818
TI  - Calculations of V-V transfer rates in H2 and comparison with experiment.
AB  - Recent observations on VV transfer in H(2) have shown interesting results. For
      nonresonant processes, comparison of the experimental rate constants with the
      results of previous semiclassical calculations, quantum oscillators/classical
      rotors coupled via classical collisions, showed the theoretical rate constants to
      be too slow by a factor of 3 or more. The semiclassical rate constant of the
      resonant VV process (v = 1 + v = 0 --> v = 0 + v = 1) was also found to be too
      slow, by more than an order of magnitude, compared with the experimental rate.
      Further, the semiclassical model predicted the value of k(1,1-->0,2) to exceed
      that of k(1,0-->0,1), but the experimental data shows it to be a factor of
      approximately 2 less. In this work we employ an accurate interaction potential
      for the H(2)-H(2) system, and treat both rotation and vibration of the diatoms as
      coupled quantum-mechanical degrees of freedom. These new calculated results are
      in better overall agreement with the near-resonant experimental values, but the
      calculated rate constants are a factor of 2 to 3 larger than experiment for the
      nonresonant processes.

PMID- 19115819
TI  - Electrostatic polarization effects and hydrophobic hydration in ethanol-water
      solutions from molecular dynamics simulations.
AB  - Nonadditive electrostatic force fields based on the charge equilibration
      formalism coupled with long time-scale molecular dynamics simulations are used to
      investigate the microscopic structural aspects of hydrophobic hydration in
      ethanol-water solutions. Employing a combination of polarizable ethanol and water
      force fields (developed independently), we find that solution properties are
      satisfactorily reproduced across the ethanol mole fraction range between 0.1 and
      0.9. Solution densities are predicted within 3.6% of experimental measurements,
      while excess mixing enthalpies are overestimated as in earlier studies. The
      solvation free energy of ethanol in infinite dilution is determined via
      thermodynamic integration to be 5.70 +/- 0.23 kcal/mol, overestimating the free
      energetics of solvation relative to experiment (5.01 kcal/mol). Bulk solution
      dielectric constants and diffusion constants reproduce experimental trends and
      are in reasonable agreement across the ethanol concentration range studied.
      Because of explicit accounting of induction effects, ethanol and water exhibit
      varying molecular dipole moment distributions with concentration. The polarizable
      ethanol model, possessing higher condensed-phase polarizability relative to the
      TIP4P-FQ water model (4.54 A(3) versus 1.1 A(3), respectively), displays greater
      variation upon perturbation by the electric field of water. With regard to
      hydrophobic hydration, the current force fields indicate positive hydrogen
      bonding excess for water in the dilute ethanol concentration range, consistent
      with previous theoretical and experimental studies. Strikingly, we find that
      there are both positive and negative hydrogen bond excess contributions within
      the first hydration shell of both the ethanol hydroxyl oxygen and ethylene carbon
      atoms. The larger positive contributions dominate the overall hydrogen bonding
      patterns to yield overall net positive excesses. Moreover, we do not find
      evidence of excess hydrogen bonding vicinal to the nonpolar moieties as has been
      suggested based on the "iceberg"-like models proposed by Frank and Evans. The
      present results suggest negative excess in the regions surrounding the alkyl
      groups that vis-a-vis corresponds to a reduction in the average molecular dipole
      moment of resident water molecules due to smaller dipole induction in the weaker
      electrostatic fields of the nonpolar groups.

PMID- 19115820
TI  - Effect of hydrogen-bonding complexation on the interfacial behavior of
      poly(isoprene)-b-poly(ethylene oxide) and poly(isoprene)-b-poly(acrylic acid)
      Langmuir monolayers.
AB  - The effect of hydrogen-bonding complexation on the interfacial behavior of
      poly(isoprene)-b-poly(ethylene oxide) (PI-b-PEO) diblock copolymer at the air
      water interface has been investigated by Langmuir balance and neutron
      reflectivity. PI-b-PEO forms Langmuir monolayers with PI as the anchoring block.
      Introduction of a second diblock, poly(isoprene)-b-poly(acrylic acid) (PI-b-PAA)
      yields PI-b-PEO/PI-b-PAA mixed layers with interfacial behavior that is pH
      dependent. At pH 10.0 and 5.7, the compression (pi-A) isotherms exhibit three
      regions that are characteristic of PEO-type tethered layers, (i) a low-pressure 2
      D "pancake" region (region I), (ii) a pseudoplateau where PEO segments desorb and
      are immerse in the subphase (region II), and (iii) a steep pressure rise region
      commonly considered as the "brush" regime (region III). At pH 2.5, on the other
      hand, the pi-A isotherm shows only two regions, (I) and (III). This novel
      behavior is attributed to hydrogen-bonding complexation between the undissociated
      carboxylic acids and the PEO, forming very compact layers. It appears that
      desorption of PEO segments is hindered as a consequence of this complexation.
      Furthermore, no brush-like structure is observed in region III of the isotherml;
      thus, the steep rise in surface pressure in this case arises primarily from
      interactions of the anchoring block. The hydrogen-bonded complex of PI-b-PEO/PI-b
      PAA monolayers thus shows enhanced surface stability.

PMID- 19115822
TI  - Modifying properties of aqueous cetyltrimethylammonium bromide with external
      additives: ionic liquid 1-hexyl-3-methylimidazolium bromide versus cosurfactant n
      hexyltrimethylammonium bromide.
AB  - Understanding the effect of external additives on the properties of aqueous
      surfactant solutions is of utmost importance due to widespread applications of
      surfactant-based systems. Role of ionic liquids (ILs) in this regard may turn out
      to be crucial as these substances are known to possess unusual properties. To
      unambiguously understand and establish the role of ILs in modifying properties of
      aqueous surfactant systems, changes in the physicochemical properties of aqueous
      cetyltrimethylammonium bromide (CTAB) upon addition of an IL 1-hexyl-3
      methylimidazolium bromide ([hmim][Br]) are compared with those when a
      cosurfactant n-hexyltrimethylammonium bromide (HeTAB) is added to aqueous CTAB.
      Important physicochemical properties, such as critical micelle concentration
      (cmc), aggregation number (N(agg)), solution conductance and microfluidity, and
      average aggregate size and polydispersity, are observed to change as either
      [hmim][Br] or HeTAB is added to aqueous CTAB; the experimental outcomes clearly
      imply the changes in most of the physicochemical properties to be significantly
      more dramatic in case of IL [hmim][Br] addition. The fact that, between the two,
      only IL [hmim][Br] may show cosolvent-type behavior at high concentrations is
      evoked to explain the differences in the behavior of the two additives. It is
      demonstrated that both [hmim][Br] and HeTAB show electrolytic as well as
      cosurfactant-type behavior within aqueous CTAB when present at low
      concentrations, with the changes in physicochemical properties being very
      similar. At high concentrations, although HeTAB still acts as a cosurfactant
      forming mixed micelles with CTAB, IL [hmim][Br] behaves partly as a cosolvent
      toward altering the physicochemical properties of aqueous CTAB. The unique role
      of IL in changing properties of aqueous surfactant systems is demonstrated.

PMID- 19115821
TI  - Extraction and assembly of tissue-derived gels for cell culture and tissue
      engineering.
AB  - Interactions with the extracellular matrix (ECM) play an important role in
      regulating cell function. Cells cultured in, or on, three-dimensional ECM
      recapitulate similar features to those found in vivo that are not present in
      traditional two-dimensional culture. In addition, both natural and synthetic
      materials containing ECM components have shown promise in a number of tissue
      engineering applications. Current materials available for cell culture and tissue
      engineering do not adequately reflect the diversity of ECM composition between
      tissues. In this paper, a method is presented for extracting solutions of
      proteins and glycoproteins from soft tissues and inducing assembly of these
      proteins into gels. The extracts contain ECM proteins specific to the tissue
      source with low levels of intracellular molecules. Gels formed from the tissue
      derived extracts have nanostructure similar to ECM in vivo and can be used to
      culture cells as both a thin substrate coating and a thick gel. This technique
      could be used to assemble hydrogels with varying composition depending upon the
      tissue source, hydrogels for three-dimensional culture, as scaffolds for tissue
      engineering therapies, and to study cell-matrix interactions.

PMID- 19115823
TI  - Tissue reactions to engineered cartilage based on poly-L-lactic acid scaffolds.
AB  - Tissue reactions against poly-L-lactic acid (PLLA) in engineered cartilage may
      influence the size or maturity of regenerative tissue. To understand the
      biological events in these reactions, we subcutaneously transplanted engineered
      constructs of PLLA scaffolds with or without human chondrocytes or atelocollagen
      in nude mice and evaluated neovascularization and macrophage activation, which
      can be assessed even in nude mice. Although not showing cartilage regeneration,
      PLLA alone demonstrated dense localization of macrophages and blood vessels, as
      well as a high level of interleukin-1 beta and tissue hemoglobin at 2 and 8
      weeks. Otherwise, constructs with PLLA and chondrocytes with or without
      atelocollagen (PLLA/cell/gel or PLLA/cell) formed mature cartilage by 8 weeks,
      which was more prominent in PLLA/cell/gel. Although accumulation of macrophages
      and blood vessels in PLLA/cell/gel and PLLA/cell was comparable with that in PLLA
      at 2 weeks, that in PLLA/cell/gel markedly decreased by 8 weeks, with blood
      vessels and macrophages excluded into non-cartilage areas. Macrophage migration
      inhibitory factor could be involved in these suppressed tissue reactions, because
      it was expressed in chondrocytes of engineered cartilage. Intense tissue
      reactions inevitably occurred in biopolymers alone, but it is possible that
      maturation of engineered cartilage suppressed these reactions, which may
      contribute to circumventing deformity or malformation of engineered tissues.

PMID- 19115824
TI  - Quantum chemical calculations of the Cl- + CH3I --> CH3Cl + I- potential energy
      surface.
AB  - Electronic structure theory calculations, using MP2 theory and the DFT
      functionals OPBE, OLYP, HCTH407, BhandH, and B97-1, were performed to
      characterize the structures, vibrational frequencies, and energies for stationary
      points on the Cl(-) + CH(3)I --> ClCH(3) + I(-) potential energy surface. The aug
      cc-pVDZ and aug-cc-pVTZ basis sets, with an effective core potential (ECP) for
      iodine, were employed. Single-point CCSD(T) calculations were performed to obtain
      the complete basis set (CBS) limit for the reaction energies. DFT was found to
      give significantly longer halide ion/carbon atom bond lengths for the ion-dipole
      complexes and central barrier transition state than MP2. BhandH, with either the
      aug-cc-pVDZ or aug-cc-pVTZ basis sets, gives good agreement with the experimental
      structures for both CH(3)I and CH(3)Cl. The frequencies of CH(3)I and CH(3)Cl,
      obtained with the different levels of theory and basis sets, are in excellent
      agreement with experiment. The major difference between the MP2 and DFT
      frequencies is for the imaginary frequency of the central barrier. Using the aug
      cc-pVTZ basis the MP2 value for this frequency ranges from 1.26 to 1.59 times
      larger than those for the DFT functionals. Thus, the MP2 and DFT theories have
      different PES shapes in the vicinity of the [Cl--CH(3)--I](-) central barrier.
      The CCSD(T)/CBS energies are in good agreement with experiments for the
      complexation energies and reaction exothermicity, with a small 1 kcal/mol
      difference for the latter. The CCSD(T)/CBS central barrier height is lower than
      values deduced by using statistical theoretical models to fit the Cl(-) + CH(3)I 
      -> ClCH(3) + I(-) experimental rate constant, which is consistent with the
      expected nonstatistical dynamics for the reaction. The BhandH energies are in
      overall best agreement with the CCSD(T) values, with a largest difference of only
      0.7 kcal/mol.

PMID- 19115825
TI  - Structure and dynamics of water confined in single-wall nanotubes.
AB  - The structure and dynamics of water confined in model single-wall carbon- and
      boron-nitride nanotubes (called SWCNT and SWBNNT, respectively) of different
      diameters have been investigated by molecular dynamics (MD) simulations at room
      temperature. The simulations were performed on periodically extended nanotubes
      filled with an amount of water that was determined by soaking a section of the
      nanotube in a water box in an NpT simulation (1 atm, 298 K). All MD production
      simulations were performed in the canonical (NVT) ensemble at a temperature of
      298 K. Water was described by the extended simple point charge (SPC/E) model. The
      wall-water interactions were varied, within reasonable limits, to study the
      effect of a modified hydrophobicity of the pore walls. We report distribution
      functions for the water in the tubes in spherical and cylindrical coordinates and
      then look at the single-molecule dynamics, in particular self-diffusion. While
      this motion is slowed down in narrow tubes, in keeping with previous findings
      (Liu et al. J. Chem. Phys. 2005, 123, 234701-234707; Liu and Wang. Phys. Rev.
      2005, 72, 085420/1-085420/4; Liu et al. Langmuir 2005, 21, 12025-12030) bulk
      water like self-diffusion coefficients are found in wider tubes, more or less
      independently of the wall-water interaction. There may, however, be an anomaly in
      the self-diffusion for the SWBNNT.

PMID- 19115826
TI  - Influence of culture medium on smooth muscle cell differentiation from human bone
      marrow-derived mesenchymal stem cells.
AB  - Human bone marrow-derived mesenchymal stem cells (hMSCs) represent an appealing
      source of smooth muscle cells (SMCs) for engineering small-diameter vascular
      grafts due to the limited availability and replicative capacity of somatic SMCs.
      However, lack of standardization of hMSC culture conditions has limited some
      progress in hMSC research. Because, at the moment, a chemically defined, serum
      free medium without growth factors is not capable of amplifying hMSCs in vitro,
      the usage of serum (either human serum or fetal bovine serum [FBS]) continues in
      hMSC research. The emergence of commercial hMSCs and hMSC media opened a series
      of questions regarding the compatibility of commercial and homemade hMSCs and
      hMSC media. In this study, two types of commonly used FBS-containing hMSC media
      MSCGM (containing 10% FBS) and MesenPro (containing 2% FBS), along with our
      homemade medium (low-glucose Dulbecco's modified Eagle's medium plus 10% selected
      lot FBS)-were compared in their ability to support SMC differentiation from
      hMSCs. The effects of FBS level, medium supplements (ascorbic acid, copper,
      etc.), and growth factors (transforming growth factor beta1) were also examined
      for their impact on SMC differentiation. It was discovered that MesenPro and
      transforming growth factor beta1 are the strongest SMC inducers from hMSCs. In
      contrast, hMSCs grown in homemade (10% Dulbecco's modified Eagle's medium) and
      commercial MSCGM media remained undifferentiated. FBS concentration did not
      affect SMC differentiation when 10% FBS was compared with 2%. Finally, the
      mechanism underlying SMC differentiation from hMSCs grown in FBS-containing
      medium was explored by following the expression changes of serum response factor
      during the establishment of hMSC culture.

PMID- 19115827
TI  - Chondrogenesis of human bone marrow mesenchymal stem cells in fibrin-polyurethane
      composites.
AB  - This study investigated whether a three-dimensional (3D) fibrin gel-polyurethane
      scaffold composite can provide an environment for chondrogenesis of human bone
      marrow mesenchymal stem cells (hMSCs) that is as supportive as pellet culture,
      which is an established model for evaluating chondrogenesis. Pellet culture was
      carried out in serum-free medium in the absence or presence of transforming
      growth factor beta 1 (TGF-beta1) and dexamethasone. hMSCs were seeded into a
      fibrin gel-biodegradable polyurethane scaffold at cell densities of 2 x 10(6), 5
      x 10(6), and 10 x 10(6) cells per scaffold and cultured in serum-free medium
      supplemented with TGF-beta1 and dexamethasone. With comparable proteoglycan
      synthesis and type I and type X collagen gene expression levels, scaffolds seeded
      with 5 x 10(6) cells expressed higher type II collagen and aggrecan gene
      transcripts than pellets on day 14. The deposition of proteoglycan and type II
      collagen was detected on the top layer of scaffolds seeded with 10 x 10(6) cells
      and was more evenly distributed in the scaffolds seeded with 5 x 10(6) cells. The
      scaffold composite culture system shows chondrogenesis of hMSCs comparable with
      that of pellet culture. Initial cell seeding density influences the ability and
      process of hMSC chondrogenesis. This study founded a basic system for cartilage
      neo-tissue formation in vitro.

PMID- 19115828
TI  - Phenotype and gene expression of human mesenchymal stem cells in alginate
      scaffolds.
AB  - Human mesenchymal stem cells (MSC) are popular candidates for tissue engineering.
      MSC are defined by their properties in two-dimensional (2D) culture systems.
      Cells in 2D are known to differ from their in vivo counterparts in cell shape,
      proliferation, and gene expression. Little is so far known about the phenotype
      and gene expression of cells in three-dimensional (3D) culture systems. To begin
      to unravel the impact of 3D versus 2D culture conditions on MSC, we have
      established MSC from adipose tissue and bone marrow in 3D cultures in alginate
      beads covalently modified with the tripeptide arginine-glycine-aspartic acid
      (RGD), the integrin-binding motif found in several molecules within the
      extracellular matrix. The MSC changed from their fibroblastoid shape (2D) to a
      small, compact shape when embedded in RGD alginate (3D). High viability was
      maintained throughout the experiment. The MSC retained expression of integrins
      known to bind RGD, and practically ceased to proliferate. Microarray analysis
      revealed that the gene expression in cells in RGD alginate was different both
      from the cells cultured in 2D and from prospectively isolated, uncultured MSC,
      but more similar to 2D cells. As alginate may be entirely dissolved, leaving the
      cells as single cell suspensions for various analyses, this represents a useful
      model for the study of cells in 3D cultures.

PMID- 19115830
TI  - Design and microwave-assisted synthesis of naphtho[2,3-f]quinoline derivatives
      and their luminescent properties.
AB  - A sequential three-component reaction of an aromatic aldehyde with an equimolar
      amount of 2-aminoanthracene and cyclic 1,3-dicarbonyl compounds (such as tetronic
      acid, 5,5-dimethyl,3-cyclohexanedione, 1,3-indanedione, 3H-chromene-2,4-dione,
      quinoline-2,4(1H, 3H)-dione and barbituric acid) in acidic medium under microwave
      irradiation has been developed. In this one-pot reaction, a series of unusual
      fused heterocyclic compounds, naphtho[2,3-f]quinoline derivatives, were
      synthesized. This method has the advantages of operational simplicity, increased
      safety for small-scale fast synthesis, and minimal environmental impact. Most
      distinctively, this new class of naphtho[2,3-f]quinoline derivatives exhibit good
      luminescent properties in the ethanol solution, which can be used potentially as
      organic electroluminescent (EL) media.

PMID- 19115831
TI  - Zero-dimensional units of ligand-bridged gallium-sulfide supertetrahedra.
AB  - The synthesis and characterization of the first anions containing two gallium
      sulfide supertetrahedra linked via an organic moiety are described.

PMID- 19115832
TI  - Conformational Closure of the Catalytic Site of Human CD38 Induced by Calcium
      (dagger) (double dagger).
AB  - First identified on the surface of lymphoids as a type II transmembrane protein,
      CD38 has now been established to have dual functions not only as a receptor but
      also as a multifunctional enzyme, catalyzing the synthesis of and hydrolysis of a
      general calcium messenger molecule, cyclic ADP-ribose (cADPR). The receptorial
      functions of CD38 include the induction of cell adhesion, differentiation,
      apoptosis, and cytokine production upon antibody ligation. Here we determined the
      crystal structure of calcium-loaded human CD38 at 1.45 A resolution which reveals
      that CD38 undergoes dramatic structural changes to an inhibited conformation in
      the presence of calcium. The structural changes are highly localized and occur in
      only two regions. The first region is part of the active site and consists of
      residues 121-141. In the presence of calcium, W125 moves 5 A into the active site
      and forms hydrophobic interactions with W189. The movement closes the active site
      pocket and reduces entry of substrates, resulting in inhibition of the enzymatic
      activity. The structural role of calcium in inducing these conformational changes
      is readily visualized in the crystal structure. The other region that undergoes
      calcium-induced changes is at the receptor region, where a highly ordered helix
      is unraveled to a random coil. The results suggest a novel conformational
      coupling mechanism, whereby protein interaction targeted at the receptor region
      can effectively regulate the enzymatic activity of CD38.

PMID- 19115833
TI  - 22-Isopolytungstate fragment [H2W22O74]14- coordinated to lanthanide ions.
AB  - The novel polyanions [Ln(2)(H(2)O)(10)W(22)O(71)(OH)(2)](8-) (Ln = La (1), Ce
      (2), Tb (3), Dy (4), Ho (5), Er (6), Tm (7), Yb (8), Lu (9), Y (10)) have been
      synthesized by reaction of WO(4)(2-) and lanthanide ions in acidic aqueous
      medium. The low symmetry (C(i)) polyanion family
      [Ln(2)(H(2)O)(10)W(22)O(71)(OH)(2)](8-) consists of the isopolyanion
      [H(2)W(22)O(74)](14-) and two {Ln(H(2)O)(5)}(3+) supporting units. The
      [H(2)W(22)O(74)](14-) cluster, which consists of two undecatungstate {W(11)}
      fragments, acts as a tridentate ligand to two Ln(3+) ions. Polyanions 1-10 are
      isostructural, and the coordination number of the lanthanide ions correlates with
      their sizes. All compounds have been fully characterized in the solid state by
      Fourier transform infrared spectroscopy, single-crystal X-ray diffraction,
      thermogravimetric analysis, and elemental analysis. Single-crystal X-ray
      diffraction analyses show that 1-10 crystallize as sodium salts in the triclinic
      space group P1.

PMID- 19115834
TI  - Imaging and detection of single molecule recognition events on organic
      semiconductor surfaces.
AB  - The combination of organic thin film transistors and biological molecules could
      open new approaches for the detection and measurement of properties of biological
      entities. To generate specific addressable binding sites on such substrates, it
      is necessary to determine how single biological molecules, capable of serving as
      such binding sites behave upon attachment to semiconductor surfaces. Here, we use
      a combination of high-resolution atomic force microscopy topographical imaging
      and single molecule force spectroscopy (TREC), to study the functionality of
      antibiotin antibodies upon adsorption on pentacene islands, using biotin
      functionalized, magnetically coated AFM tips. The antibodies could be stably
      adsorbed on the pentacene, preserving their functionality of recognizing biotin
      over the whole observation time of more than one hour. We have resolved
      individual antigen binding sites on single antibodies for the first time. This
      highlights the resolution capacity of the technique.

PMID- 19115835
TI  - Unexpected benefits of rapid growth rate for III-V nanowires.
AB  - In conventional planar growth of bulk III-V materials, a slow growth rate favors
      high crystallographic quality, optical quality, and purity of the resulting
      material. Surprisingly, we observe exactly the opposite effect for Au-assisted
      GaAs nanowire growth. By employing a rapid growth rate, the resulting nanowires
      are markedly less tapered, are free of planar crystallographic defects, and have
      very high purity with minimal intrinsic dopant incorporation. Importantly,
      carrier lifetimes are not adversely affected. These results reveal intriguing
      behavior in the growth of nanoscale materials, and represent a significant
      advance toward the rational growth of nanowires for device applications.

PMID- 19115836
TI  - Isolation, structure elucidation, and biological activity of virgineone from
      Lachnum Wirgineum using the genome-wide Candida albicans fitness test.
AB  - A glycosylated tetramic acid, virgineone (1), was isolated from saprotrophic
      Lachnum virgineum. The antifungal activity of the fermentation extract of L.
      virgineum was characterized in the Candida albicans fitness test as
      distinguishable from other natural products tested. Bioassay-guided fractionation
      yielded 1, a tyrosine-derived tetramic acid with a C-22 oxygenated chain and a
      beta-mannose. It displayed broad-spectrum antifungal activity against Candida
      spp. and Aspergillus fumigatus with a MIC of 4 and 16 microg/mL, respectively.
      Virgineone was also identified in a number of Lachnum strains collected from
      diverse geographies and habitats.

PMID- 19115837
TI  - Homotyrosine-containing cyanopeptolins 880 and 960 and anabaenopeptins 908 and
      915 from Planktothrix agardhii CYA 126/8.
AB  - Two homotyrosine-bearing cyanopeptolins are described from Planktothrix agardhii
      CYA 126/8. The compounds feature a common homotyrosine-containing
      cyclohexadepsipeptide and differ by sulfation of an exocyclically located 2-O
      methyl-d-glyceric acid residue. In addition we describe two anabaenopeptins,
      which contain two homotyrosine residues, one of which is N-methylated. The
      anabaenopeptins have a common cyclopentapeptide portion and differ in the amino
      acid linked to it via an ureido bond, arginine and tyrosine, respectively.

PMID- 19115839
TI  - Synthesis and cytotoxicity of bidesmosidic betulin and betulinic acid saponins.
AB  - The naturally occurring cytotoxic saponin 28-O-beta-d-glucopyranosylbetulinic
      acid 3beta-O-alpha-l-arabinopyranoside (3) was easily synthesized along with
      seven bidesmosidic saponins starting from the lupane-type triterpenoids betulin
      (1) and betulinic acid (2). As highlighted by the preliminary cytotoxicity
      evaluation against A549, DLD-1, MCF7, and PC-3 human cancer cell lines, the
      bidesmosidic betulin saponin 22a, bearing alpha-l-rhamnopyranoside moieties at
      both C-3 and C-28 positions, was determined to be a potent cytotoxic agent
      (IC(50) 1.8-1.9 microM).

PMID- 19115838
TI  - Isolation, structure, and antibacterial activities of lucensimycins D-G,
      discovered from Streptomyces lucensis MA7349 using an antisense strategy.
AB  - Bacterial resistance to existing antibiotics continues to grow, necessitating the
      discovery of new compounds of this type. Antisense-based whole-cell target-based
      screening is a new and highly sensitive antibiotic discovery approach that has
      led to a number of new natural product antibiotics. Screening with a rpsD
      sensitized strain led to the discovery of a number of natural product polyketides
      from Streptomyces lucensis. Complete workup of the fermentation extract of this
      strain allowed for the isolation of seven new compounds, lucensimycins A-G (1-3,
      4a, 5-7), with varying degrees of antibacterial activities. Lucensimycin E (5)
      exhibited the best activity and showed MIC values of 32 microg/mL against
      Staphylococcus aureus and 8 microg/mL against Streptococcus pneumoniae. The
      isolation, structure elucidation, and antibacterial activities of four new
      members, lucensimycins D-G, are described. Lucensimycins D (4a) and E (5) are N
      acetyl-l-cysteine adducts of lucensimycin A (1). Semisynthesis of lucensimycins D
      and E from lucensimycin A has also been described. Lucensimycins F and G are myo
      inositolyl-alpha-2-amino-2-deoxy-l-idosyl amide derivatives of lucensimycins D
      and E, respectively. The relative configuration of these compounds was
      determined, in part, by molecular dynamics simulations.

PMID- 19115840
TI  - Practical synthesis of 3beta-amino-5-cholestene and related 3beta-halides
      involving i-steroid and retro-i-steroid rearrangements.
AB  - Derivatives of 3beta-amino-5-cholestene (3beta-cholesterylamine) are of
      substantial interest as cellular probes and have potential medicinal
      applications. However, existing syntheses of 3beta-amino-5-cholestene are of
      limited preparative utility. We report here a practical method for the
      stereoselective preparation of 3beta-amino-5-cholestene, 3beta-chloro-5
      cholestene, 3beta-bromo-5-cholestene, and 3beta-iodo-5-cholestene from
      inexpensive cholesterol. A sequential i-steroid/retro-i-steroid rearrangement
      promoted by boron trifluoride etherate and trimethylsilyl azide converted cholest
      5-en-3beta-ol methanesulfonate to 3beta-azido-cholest-5-ene with retention of
      configuration in 93% yield.

PMID- 19115841
TI  - "Click, click, cyclize": a DOS approach to sultams utilizing vinyl sulfonamide
      linchpins.
AB  - A diversity-oriented synthesis (DOS) strategy termed "Click, Click, Cyclize" is
      reported. This approach relies on functional group (FG) pairing between a vinyl
      sulfonamide and an array of functional groups to synthesize skeletally diverse
      sultams. Several FG pairing pathways on central tertiary vinyl sulfonamide
      linchpins have been developed including intramolecular Heck, aza-Michael, ring
      closing enyne metathesis, Pauson-Khand, and chemoselective oxidation/Baylis
      Hillman reactions.

PMID- 19115843
TI  - Carbonic anhydrase inhibitors. Comparison of chlorthalidone and indapamide X-ray
      crystal structures in adducts with isozyme II: when three water molecules and the
      keto-enol tautomerism make the difference.
AB  - Thiazide diuretics inhibit all mammalian isoforms of carbonic anhydrase (CA, EC
      4.2.1.1) with a different profile as compared to classical inhibitors. Acting as
      moderate-weak inhibitors of CA II and CA I, chlorthalidone and indapamide
      considerably inhibit other isozymes among the 16 CAs present in vertebrates.
      These compounds show a different behavior against CAs I and II, with
      chlorthalidone being 18.3 times more potent against CA II and 150 times more
      potent against CA I, as compared to indapamide. In the X-ray crystal structures
      of the CA II-chlorthalidone adduct three active site water molecules interacting
      with the inhibitor scaffold were observed that lack in the corresponding
      indapamide adduct. Chlorthalidone bound within the active site is in an enolic
      tautomeric form, with the OH moiety participating in two strong hydrogen bonds
      with Asn67 and a water molecule. This binding mode may be exploited for designing
      better CA II inhibitors.

PMID- 19115845
TI  - First Cdc7 kinase inhibitors: pyrrolopyridinones as potent and orally active
      antitumor agents. 2. Lead discovery.
AB  - Cdc7 kinase is a key regulator of the S-phase of the cell cycle, known to promote
      the activation of DNA replication origins in eukaryotic organisms. Cdc7
      inhibition can cause tumor-cell death in a p53-independent manner, supporting the
      rationale for developing Cdc7 inhibitors for the treatment of cancer. In this
      paper, we conclude the structure-activity relationships study of the 2-heteroaryl
      pyrrolopyridinone class of compounds that display potent inhibitory activity
      against Cdc7 kinase. Furthermore, we also describe the discovery of 89S, [(S)-2
      (2-aminopyrimidin-4-yl)-7-(2-fluoro-ethyl)-1,5,6,7-tetrahydropyrrolo[3,2
      c]pyridin-4-one], as a potent ATP mimetic inhibitor of Cdc7. Compound 89S has a
      Ki value of 0.5 nM, inhibits cell proliferation of different tumor cell lines
      with an IC50 in the submicromolar range, and exhibits in vivo tumor growth
      inhibition of 68% in the A2780 xenograft model.

PMID- 19115846
TI  - Tandem enyne metathesis-metallotropic [1,3]-shift for a concise total syntheses
      of (+)-asperpentyn, (-)-harveynone, and (-)-tricholomenyn A.
AB  - A tandem reaction sequence involving relay metathesis-induced enyne RCM and
      metallotropic [1,3]-shift is an effective tool to construct cyclic alkenes with
      embedded 1,5-dien-3-yne moieties from acyclic precursors containing a 1,3-diyne.
      Total syntheses of (+)-asperpentyn, (-)-harveynone, and (-)-tricholomenyn A have
      been accomplished by implementing this metathesis-based tandem reaction sequence
      as the key step.

PMID- 19115847
TI  - Heart rate and heart-rate variability responses to acute and chronic stress in a
      wild-caught passerine bird.
AB  - The cardiovascular-stress response has been studied extensively in laboratory
      animals but has been poorly studied in naturally selected species. We determined
      the relative roles of the sympathetic nervous system (SNS) and the
      parasympathetic nervous system (PNS) in regulating stress-induced changes in
      heart rate (HR) in wild-caught European starlings (Sturnus vulgaris). In both
      heart-rate variability (HRV) analysis and receptor blockade (atropine and
      propranolol) experiments, baseline HR was controlled predominantly by the PNS,
      whereas the increase in HR resulting from acute restraint stress was controlled
      predominantly by the SNS. These results indicate similar cardiac control of
      baseline and acute-stress-induced HR in wild-caught starlings and mammals. We
      further investigated HR responses during chronic stress. Driven primarily by
      changes in PNS regulation, baseline HR increased during the day but decreased at
      night. In addition, elevated HRs during acute restraint stress were attenuated
      throughout chronic stress and were accompanied by decreased HRV. This suggested
      that increased SNS drive elevated HR, but the attenuated HR response combined
      with resistance to the SNS blocker propranolol suggested that the sympathetic
      signal was less effective during chronic stress. Overall, chronic stress in wild
      caught starlings elicited profound changes in cardiac function that were
      primarily regulated by changes in the PNS.

PMID- 19115849
TI  - Curvature-directed assembly of gold nanocubes, nanobranches, and nanospheres.
AB  - Gold nanocubes, nanobranches, and nanospheres were prepared in high yields using
      a seeded growth method in the presence of cationic surfactants. The resultant Au
      nanostructures are encapsulated with a surfactant bilayer and positively charged.
      The nanocubes are single-crystalline and enclosed with low-index facets. The
      nanobranches and nanospheres are multiply twinned. Each nanobranch possesses a
      varying number of sharp tips, which expose high-index facets. Glutathione was
      used to induce the assembly of the Au nanostructures, including both
      monocomponent (nanocubes and nanobranches) and bicomponent (nanocube-nanosphere
      and nanobranch-nanosphere) systems. The assembly was observed to occur
      predominantly at the vertices of the nanocubes and the sharp tips of the
      nanobranches. This curvature-directed assembly can be attributed to the
      preferential bonding of glutathione to the highly curved sites of the Au
      nanostructures. The fact that the curvature-directed assembly occurs for both the
      single-crystalline nanocubes and the multiply twinned nanobranches strongly
      suggests that the preferential bonding of glutathione to the curved sites is due
      to the less ordered surfactant bilayer at the curved sites than on the flat
      surfaces.

PMID- 19115848
TI  - Preparation of the binary technetium bromides: TcBr3 and TcBr4.
AB  - TcBr(3) (1) and TcBr(4) (2) were synthesized by reaction of Tc metal with
      elemental bromine at 400 degrees C. Single crystal XRD measurements indicate that
      TcBr(3) crystallizes in the orthorhombic space group Pmmn (a = 11.0656(2) A, b =
      5.9717(1) A, c = 6.3870(1) A). The structure consists of infinite chains of face
      sharing TcBr(6) octahedra with a regular alternation of short and long Tc-Tc
      distances (2.8283(4) A, 3.1434(4) A). TcBr(4) crystallizes in the orthorhombic
      space group Pbca (a = 6.3237(5) A, b = 12.1777(9) A, c = 14.7397(11) A). TcBr(4)
      contains infinite chains of edge-sharing TcBr(6) octahedra with no apparent metal
      metal bond (Tc-Tc = 3.7914(4) A). Technetium tribromide is isomorphous with
      RuBr(3) and MoBr(3), while TcBr(4) is isomorphous with PtBr(4) and OsBr(4).

PMID- 19115850
TI  - Peptide secondary structures in the gas phase: consensus motif of N-linked
      glycoproteins.
AB  - The possibility of secondary structure acting as a primary determinant in
      nature's choice of the consensus sequon, NXS/T in all N-linked glycoproteins, has
      been addressed by determining the intrinsic secondary structures of the capped
      oligopeptide, Ac-NGS-NHBn, and two "mutants", Ac-QGS-NHBn and Ac-NPS-NHBn, by use
      of infrared laser ion dip spectroscopy in the gas phase coupled with ab initio
      and density functional theory calculation. Their global minimum energy
      conformations, exclusively or preferentially populated in all three peptides,
      display marked differences. NGS adopts an open, S-shaped backbone conformation
      rather than the C(10) "Asx" turn structure that all previous measurements have
      identified in solution; the difference can be related to the high dipole moment
      of the "Asx" conformation and structural selection in a polar environment. QGS
      adopts a similar but more rigid backbone structure, supported by markedly
      stronger hydrogen bonds. NPS adopts an Asx turn coupled with a C(10) beta-turn
      backbone conformation, a structure also adopted in a crystal environment. These
      and other more subtle structural differences, particularly those involving
      interactions with the carboxamide side chain, provide strong evidence for the
      operation of structural constraints, and a potential insight into the unique
      reactivity of the asparagine side chain toward enzymatic glycosylation.

PMID- 19115851
TI  - Synthesis of an electromagnetic wave absorber for high-speed wireless
      communication.
AB  - Millimeter waves (30-300 GHz) are starting to be used in next generation high
      speed wireless communications. To avoid electromagnetic interference in this
      wireless communication, finding a suitable electromagnetic wave absorber in the
      millimeter wave range is an urgent matter. In this work, we prepared a high
      performance millimeter wave absorber composed of a series of aluminum-substituted
      epsilon-iron oxide, epsilon-Al(x)Fe(2-x)O(3), nanomagnets (0 < or = x < or =
      0.40) with a particle size between 25 and 50 nm. The materials in this series
      have an orthorhombic crystal structure in the Pna2(1) space group, which has four
      nonequivalent Fe sites and Al ion that predominantly occupies the tetrahedral
      [FeO(4)] site. The field-cooled magnetization curves showed that the T(C) values
      were 448, 480, and 500 K for x = 0.40, 0.21, and 0, respectively. The
      magnetization versus external magnetic field showed that the coercive field H(c)
      values at 300 K were 10.2, 14.9, and 22.5 kOe for x = 0.40, 0.21, and 0,
      respectively. The millimeter wave absorption properties were measured at room
      temperature by terahertz time domain spectroscopy. The frequencies of the
      absorption peaks for x = 0.40, 0.30, 0.21, 0.09, 0.06, and 0 were observed at
      112, 125, 145, 162, 172, and 182 GHz, respectively. These absorptions are due to
      the natural resonance achieved by the large magnetic anisotropies in this series.
      Such frequencies are the highest ones for magnetic materials. Because aluminum is
      the third most abundant atom, aluminum-substituted epsilon-iron oxide is very
      economical, and thus these materials are advantageous for industrial
      applications.

PMID- 19115853
TI  - Insertion polymerization of acrylate.
AB  - Multiple insertions of acrylate in copolymerization with ethylene, and an
      insertion homo-oligomerization of methyl acrylate were observed for the first
      time. Key to these findings, and to mechanistic insights reported, are labile
      substituted complexes as catalyst precursors.

PMID- 19115852
TI  - Protein cold denaturation as seen from the solvent.
AB  - Unlike most ordered molecular systems, globular proteins exhibit a temperature of
      maximum stability, implying that the structure can be disrupted by cooling. This
      cold denaturation phenomenon is usually linked to the temperature-dependent
      hydrophobic driving force for protein folding. Yet, despite the key role played
      by protein-water interactions, hydration changes during cold denaturation have
      not been investigated experimentally. Here, we use water-(17)O spin relaxation to
      monitor the hydration dynamics of the proteins BPTI, ubiquitin, apomyoglobin, and
      beta-lactoglobulin in aqueous solution from room temperature down to -35 degrees
      C. To access this temperature range without ice formation, we contained the
      protein solution in nonperturbing picoliter emulsion droplets. Among the four
      proteins, only the destabilized apomyoglobin was observed to cold denature.
      Ubiquitin was found to be thermodynamically stable at least down to -32 degrees
      C, whereas beta-lactoglobulin is expected to be unstable below -5 degrees C but
      remains kinetically trapped in the native state. When destabilized by 4 M urea,
      beta-lactoglobulin cold denatures at 10 degrees C, as found previously by other
      methods. As seen from the solvent, the cold-denatured states of apomyoglobin in
      water and beta-lactoglobulin in 4 M urea are relatively compact and are better
      described as solvent-penetrated than as unfolded. This finding challenges the
      popular analogy between cold denaturation and the anomalous low-temperature
      increase in aqueous solubility of nonpolar molecules. Our results also suggest
      that the reported cold denaturation at -20 degrees C of ubiquitin encapsulated in
      reverse micelles is caused by the low water content rather than by the low
      temperature.

PMID- 19115854
TI  - Balance of beneficial and deleterious health effects of quinones: a case study of
      the chemical properties of genistein and estrone quinones.
AB  - Substances containing a phenolic moiety are often metabolized to quinones whose
      high reactivity makes them difficult to study. Some of these precursors have
      clear health benefits, and some quinones themselves are used in cancer therapy,
      whereas others are deleterious. For example, dietary intake of phytoestrogen,
      genistein (Gen), seems to play a preventive role in breast cancer (BC) whereas
      prolonged exposure to chemically similar mammalian estrogens is clearly
      associated with elevated incidence of BC. Although both can be metabolized to
      reactive quinones, the catechol estrogen quinones (CEQs) modify DNA by redox
      cycling and/or depurination via a Michael addition. Here, we report an
      investigation of the chemical reactivity of Gen and estrone quinones to determine
      the chemical differences of these two biologically important molecules. The
      catechol genistein quinone (CGenQ), has a half-life of 4 +/- 1 s under
      physiological condition, as determined by glutathione trapping. It disappears by
      reacting with H2O to give a dihydrate, CGenQ x (H2O)2, whose structure was proved
      by NMR. Under reductive conditions, CGenQ x (H2O)2 is readily reduced to reform
      the catechol genistein (CGen). This reversible oxidation of CGen to CGenQ and the
      prompt moderation of its reactivity by hydration to CGenQ x (H2O)2 effectively
      hinders any redox cycling or depurination reaction of CGenQ with DNA. Catechol
      estrogen quinones, on the other hand, are sufficiently long-lived that they can
      damage DNA via a Michael addition or by redox cycling. Although the reactivity of
      CEQ in a nonaqueous solvent is similar to that of CGenQ, its reactivity in
      aqueous media with the free Ade base is more than 600 times that of CGenQ. These
      results suggest that rapid hydration of a quinone can moderate its reactivity
      toward biomolecules, allowing them to express, for example, estrogen-like
      properties without exhibiting the deleterious properties of redox cycling or
      directly damaging DNA via depurination reactions.

PMID- 19115855
TI  - (1)H NMR-based metabolomic approach for understanding the fermentation behaviors
      of wine yeast strains.
AB  - (1)H NMR spectroscopy coupled with multivariate statistical analysis was used for
      the first time to investigate metabolic changes in musts during alcoholic
      fermentation and wines during aging. Three Saccharomyces cerevisiae yeast strains
      (RC-212, KIV-1116, and KUBY-501) were also evaluated for their impacts on the
      metabolic changes in must and wine. Pattern recognition (PR) methods, including
      PCA, PLS-DA, and OPLS-DA scores plots, showed clear differences for metabolites
      among musts or wines for each fermentation stage up to 6 months. Metabolites
      responsible for the differentiation were identified as valine, 2,3-butanediol
      (2,3-BD), pyruvate, succinate, proline, citrate, glycerol, malate, tartarate,
      glucose, N-methylnicotinic acid (NMNA), and polyphenol compounds. PCA scores
      plots showed continuous movements away from days 1 to 8 in all musts for all
      yeast strains, indicating continuous and active fermentation. During alcoholic
      fermentation, the highest levels of 2,3-BD, succinate, and glycerol were found in
      musts with the KIV-1116 strain, which showed the fastest fermentation or highest
      fermentative activity of the three strains, whereas the KUBY-501 strain showed
      the slowest fermentative activity. This study highlights the applicability of NMR
      based metabolomics for monitoring wine fermentation and evaluating the
      fermentative characteristics of yeast strains.

PMID- 19115857
TI  - The potential for evolutionary responses to cell-lineage selection on growth form
      and its plasticity in a red seaweed.
AB  - Despite much theoretical discussion on the evolutionary significance of
      intraclonal genetic variation, particularly for modular organisms whose lack of
      germ-soma segregation allows for variants arising in clonal growth to contribute
      to evolutionary change, the potential of this variation to fuel adaptation
      remains surprisingly untested. Given intraclonal variation, mitotic cell
      lineages, rather than sexual offspring, may frequently act as units of selection.
      Here, we applied artificial selection to such lineages in the branching red
      seaweed Asparagopsis armata, targeting aspects of clonal growth form and growth
      form plasticity that enhance light acquisition on patchy subtidal reefs and
      predicting that a genetic basis to intraclonal variation may promote significant
      responses that cannot accompany phenotypic variation alone. Cell-lineage
      selection increased variation in branch proliferation among A. armata genets and
      successfully altered its plasticity to light. Correlated responses in the
      plasticity of branch elongation, moreover, showed that cell-lineage selection may
      be transmitted among the plasticities of growth-form traits in A. armata via
      pleiotropy. By demonstrating significant responses to cell-lineage selection on
      growth-form plasticity in this seaweed, our study lends support to the notion
      that intraclonal genetic variation may potentially help clonal organisms to
      evolve adaptively in the absence of sex and thereby prove surprisingly resilient
      to environmental change.

PMID- 19115859
TI  - Self-assembly of dendritic crowns into chiral supramolecular spheres.
AB  - The synthesis and structural and retrostructural analysis of a library of
      dendronized cyclotriveratrylene containing seven nonchiral and seven chiral self
      assembling dendrons is reported. These dendronized cyclotriveratrylenes exhibit a
      crown conformation that we named dendritic crown. Selected examples of dendritic
      crowns self-assemble into helical pyramidal columns that self-organize into
      columnar crystals or into 2-D columnar hexagonal lattices with intracolumnar
      order. A second group of dendritic crowns self-assembles into helical pyramidal
      columns and spherical supramolecular dendrimers that self-organize into cubic and
      tetragonal lattices. A third group of dendritic crowns self-assembles only in
      spherical supramolecular dendrimers. The helical pyramidal columns and spherical
      supramolecular dendrimers assembled from dendronized cyclotriveratrylene
      containing nonchiral dendrons are chiral but racemic while those generated from
      chiral dendrons exhibit amplified chirality. Structural analysis by a combination
      of X-ray diffraction methods and CD experiments demonstrated a new mechanism for
      the assembly of chiral supramolecular spheres that involves an intramolecular
      structure containing short fragments of helical pyramidal columns.

PMID- 19115860
TI  - A world-to-chip interface for digital microfluidics.
AB  - Digital microfluidics (DMF) is a fluid handling technique that enables
      manipulation of discrete droplets on an array of electrodes. There is
      considerable enthusiasm for this method because of the potential for array-based
      screening applications. A limitation for DMF is nonspecific adsorption of
      reagents to device surfaces. If a given device is used to actuate multiple
      reagents, this phenomenon can cause undesirable cross-contamination. A second
      limitation for DMF (and all other microfluidic systems) is the "world-to-chip"
      interface; it is notoriously difficult to deliver reagents and samples to such
      systems without compromising the oft-hyped advantages of rapid analyses and
      reduced reagent consumption. We introduce a new strategy for digital
      microfluidics, in which a removable plastic "skin" is used to (a) eliminate cross
      contamination and (b) bridge the world-to-chip interface. We demonstrated the
      utility of this format by implementing on-chip protein digestion on immobilized
      enzyme depots. This new method has the potential to transform DMF from being a
      curiosity for aficionados into a technology that is useful for biochemical
      applications at large.

PMID- 19115856
TI  - Enrichment of cancer cells using aptamers immobilized on a microfluidic channel.
AB  - This work describes the development and investigation of an aptamer modified
      microfluidic device that captures rare cells to achieve a rapid assay without
      pretreatment of cells. To accomplish this, aptamers are first immobilized on the
      surface of a poly(dimethylsiloxane) microchannel, followed by pumping a mixture
      of cells through the device. This process permits the use of optical microscopy
      to measure the cell-surface density from which we calculate the percentage of
      cells captured as a function of cell and aptamer concentration, flow velocity,
      and incubation time. This aptamer-based device was demonstrated to capture target
      cells with >97% purity and >80% efficiency. Since the cell capture assay is
      completed within minutes and requires no pretreatment of cells, the device
      promises to play a key role in the early detection and diagnosis of cancer where
      rare diseased cells can first be enriched and then captured for detection.

PMID- 19115861
TI  - Langmuir 25th anniversary.

PMID- 19115862
TI  - Synthesis, self-assembly, and photophysical behavior of oligo phenylene
      ethynylenes: from molecular to supramolecular properties.
AB  - A pair of cationic phenylene ethynylene oligomers (OPEs) have been synthesized,
      and their optical properties have been studied in solution with and without added
      scaffold materials, including carboxymethylcellulose, carboxymethylamylose, and
      Laponite. The OPEs are strongly fluorescent in methanol solution, but in water,
      the fluorescence yield is suppressed. The addition of scaffolds to aqueous
      solutions of OPEs leads to a red shift in the absorption and in most cases a
      significant increase in the fluorescence quantum yield. The effects most likely
      arise because of template-induced formation of linear J-dimers or possibly
      because of planarization, which give rise to an effective increase in the
      conjugation length of OPEs.

PMID- 19115863
TI  - Designing surfaces with wettability that varies in response to solute identity
      and concentration.
AB  - Surfaces with solute responsive wettability can be prepared by covalent layer-by
      layer assembly of PNIPAM-c-PNASI with 10 and 100 nm diameter aminated silica
      nanoparticles. These surfaces are found to exhibit reversible changes in surface
      wetting in response to solute anion identity and concentration, allowing surfaces
      to be switched from hydrophilic (advancing water contact angle 68 degrees ) to
      hydrophobic (advancing water contact angle 145 degrees ). The extent of the
      response to solute salts is found to be consistent with the Hofmeister series and
      with associated changes in surface roughness which result from varying degrees of
      polymer swelling in response to solute ion identity and concentration. The
      observed wettability changes on these surfaces are reversible.

PMID- 19115864
TI  - Electrochemical deposition of silver nanoparticle arrays with tunable density.
AB  - We present a new approach to fabricate arrays of silver nanoparticles (SNPs) on
      predefined positions by means of electrochemical deposition (ECD) combined with
      nanoimprint lithography (NIL). The SNPs arrangement, especially the density can
      be tuned by varying the pattern design and the preparation conditions. By this
      approach, various arrays of SNPs with feature size down to submicrometer can be
      fabricated over several square centimeters on one substrate. The SNPs arrays can
      be readily extended to other conductive substrates, which have potential
      applications in detecting and sensing fields, such as surface-enhanced raman
      scatter.

PMID- 19115865
TI  - Crystallization of soft crystals.
AB  - The crystallization of micelles formed by surfactant F127 solvated by 20% in
      water was investigated in the vicinity of a hydrophilic interface. Upon entering
      the crystalline phase from low temperature, a large correlation length develops
      without preferential texture. Upon heating, the correlation length decreases and
      Oswald ripening is observed with crystallites orienting with respect to each
      other while retaining long-range and textured correlation.

PMID- 19115866
TI  - Transition in the evaporation kinetics of water microdrops on hydrophilic
      surfaces.
AB  - We describe a technique that allows measurement of the mass and shape of sessile
      liquid microdrops during evaporation. Therefore, the microdrops are deposited by
      an inkjet onto a silicon microcantilever, and the bending and the shift in
      resonance frequency are monitored. From hydrophobized surfaces, microscopic water
      drops evaporate with the same kinetics as macroscopic drops; we verify the
      validity of known evaporation laws to drops with diameters from 100 microm to
      below 10 microm. From hydrophilic surfaces, the evaporation is slowed down during
      the last approximately 100 ms; we believe that this occurs due to flattening of
      the drops, which are then stabilized by interfacial forces and disjoining
      pressure.

PMID- 19115867
TI  - Surfactant microstructure and particle aggregation control using amphiphile
      adsorption on surface-functionalized polystyrene spheres.
AB  - Surfactant microstructure and particle aggregation control upon adding surface
      functionalized 100 nm diameter polystyrene (PS) spheres to a
      cetyltrimethylammonium bromide (CTAB)/dodecylbenzenesulfonic acid (HDBS) mixed
      surfactant system has been studied using cryogenic transmission electron
      microscopy (cryo-TEM). The key premise is that selective adsorption of surfactant
      onto the spheres, driven primarily by charge interactions, impacts surfactant
      concentrations in the solutions, thus driving structures to different,
      concentration-dependent states. A concurrent effect is the role played by
      adsorption on the clustering of the PS spheres. The effects of adsorption are
      quite pronounced when aldehyde-functionalized PS spheres are added to a small
      cationic vesicle/micelle suspension: only large vesicles remain. On the other
      hand, an anionic vesicle suspension remains unperturbed by the addition of these
      PS spheres. The addition of PS spheres to a 1:1 CTAB/HDBS mass ratio solution
      results in huge PS clusters that precipitate from the suspension. These large
      clusters are networks of PS spheres connected by surfactant bilayers arising from
      hydrophobic interactions with neutrally charged vesicles or vesicle fragments.
      These results indicate that solid surface adsorption provides a viable way to
      modify microstructures in a mixed surfactant system, with additional effects
      resulting from the aggregation of the PS particles. These effects can potentially
      be useful when surfactant composition must be changed without additional
      surfactant consumption, for rheology modification, in templated material
      synthesis, as well as in understanding situations where surfactant could
      potentially be adsorbed by neighboring solid boundaries, such as surfactant
      mediated oil recovery from porous rocks and detergency.

PMID- 19115868
TI  - Immobilization of biomolecules on poly(vinyldimethylazlactone)-containing surface
      scaffolds.
AB  - We describe the successful development of a procedure for the step-by-step
      formation of a reactive, multilayer polymer scaffold incorporating polymers based
      on 2-vinyl-4,4-dimethylazlactone (VDMA) on a silicon wafer and the
      characterization of these materials. Also discussed is the development of a
      procedure for the nonsite specific attachment of a biomolecule to a modified
      silicon wafer, including scaffolds modified via drop-on-demand (DOD) inkjet
      printing. VDMA-based polymers were used because of their hydrolytic stability and
      ability of the pendant azlactone rings to form stable covalent bonds with primary
      amines without byproducts via nucleophilic addition. This reaction proceeds
      without a catalyst and at room temperature, yielding a stable amide linkage,
      which adds to the ease of construction expected when using VDMA-based polymers.
      DOD inkjet printing was explored as an interesting method for creating surfaces
      with one or more patterns of biomolecules because of the flexibility and ease of
      pattern design.

PMID- 19115869
TI  - Effect of pH and NaCl concentration on the stability of surfactant-free foam
      films.
AB  - The stability of surfactant-free foam films was studied in NaCl solutions of
      varying concentration and pH using the thin film pressure balance (TFPB)
      technique. In pure water, it was not possible to produce foam films due to weak
      film elasticity and the strong attractive hydrophobic force in foam films,
      despite the presence of strong repulsive double-layer force. In the presence of a
      very small amount of an electrolyte, however, the hydrophobic force was dampened,
      allowing metastable foam films to form. As the NaCl concentration was raised
      above 10(-6) M, the film stability diminished as a result of double-layer
      compression. The TFPB technique was also used to measure the equilibrium film
      thicknesses (H(e)) in 10(-5) M NaCl solutions of varying pH; H(e) reached a
      maximum of approximately 130 nm at pH 6.0-7.3, and decreased on either side of
      this pH range as a result of the increased ionic strength caused by the HCl and
      NaOH added to control the pH. The hydrophobic force in surfactant-free foam films
      was maximum at pH 7.3, where the concentration of electrolytes, including that of
      H(2)CO(3) species, was minimum.

PMID- 19115870
TI  - Orthogonal enzymatic reactions for the assembly of proteins at electrode
      addresses.
AB  - The ability to interface proteins to device surfaces is important for a range of
      applications. Here, we enlist the unique capabilities of enzymes and biologically
      derived polymers to assemble target proteins to electrode addresses. First, the
      stimuli-responsive aminopolysaccharide chitosan is directed to assemble at the
      electrode address in response to electrode-imposed signals. The electrodeposited
      chitosan film serves as the biodevice interface for subsequent protein assembly.
      Next, tyrosinase is used to catalyze grafting of a protein or peptide tether to
      the chitosan film. Finally, microbial transglutaminase (mTG) catalyzes the
      assembly of target proteins to the tether. mTG covalently links proteins through
      their glutamine (Gln) and lysine (Lys) residues. Since Gln and Lys residues of
      globular proteins are often inaccessible to mTG, we engineered our target
      proteins to have fusion tags with added Gln or Lys residues. This assembly method
      employs the electrical signal to confer spatial selectivity (during chitosan
      electrodeposition) and employs the enzymes to confer chemical selectivity (i.e.,
      amino acid residue selectivity). Further, this method is mild, since no reactive
      reagents or protection steps are required, and all steps are performed in aqueous
      solution. These results demonstrate the potential for employing biological
      materials and mechanisms to biofabricate the biodevice interface.

PMID- 19115871
TI  - Adsorption behavior of mercury on functionalized aspergillus versicolor mycelia:
      atomic force microscopic study.
AB  - The adsorption characteristics of mercury on Aspergillus versicolor mycelia have
      been studied under varied environments. The mycelia are functionalized by carbon
      disulfide (CS(2)) treatment under alkaline conditions to examine the enhance
      uptake capacity and explore its potentiality in pollution control management. The
      functionalized A. versicolor mycelia have been characterized by scanning electron
      microscopy-energy dispersive X-ray analysis (SEM-EDXA), attenuated total
      reflection infrared (ATR-IR), and atomic force microscopy (AFM) probing. SEM and
      AFM images exhibit the formation of nanoparticles on the mycelial surface. ATR-IR
      profile confirms the functionalization of the mycelia following chemical
      treatment. ATR-IR and EDXA results demonstrate the binding of the sulfur groups
      of the functionalized mycelia to the mercury and consequent formation metal
      sulfide. AFM study reveals that the mycelial surface is covered by a layer of
      densely packed domain like structures. Sectional analysis yields significant
      increase in average roughness (R(rms)) value (20.5 +/- 1.82 nm) compared to that
      of the pristine mycelia (4.56 +/- 0.82 nm). Surface rigidity (0.88 +/- 0.06 N/m)
      and elasticity (92.6 +/- 10.2 MPa) obtained from a force distance curve using
      finite element modeling are found to increase significantly with respect to the
      corresponding values of (0.65 +/- 0.05 N/m and 32.8 +/- 4.5 MPa) of the
      nonfunctionalized mycelia. The maximum mercury adsorption capacity of the
      functionalized mycelia is observed to be 256.5 mg/g in comparison to 80.71 mg/g
      for the pristine mycelia.

PMID- 19115872
TI  - A novel application of quaternary ammonium compounds as antibacterial hybrid
      coating on glass surfaces.
AB  - A hybrid coating is prepared on a glass surface by a sol-gel process using
      tetraethoxysilane (TEOS) and Q(4)N(+)-Si(OR)(3). Transparent coatings with smooth
      surfaces were investigated against both Gram-positive (Escherichia coli) and Gram
      negative bacteria (Staphylococcus aureus). A rapid decrease of the count for both
      strains was observed within 72 h. A significant correlation has been observed
      between the concentration of Q(4)N(+)-Si(OR)(S) and the antibacterial activity
      which has been thoroughly investigated.

PMID- 19115873
TI  - Water diffusion in bicelles and the mixed bicelle model.
AB  - To test a prediction of the mixed bicelle model, stimulated echo (STE) pulsed
      field gradient (PFG) (1)H nuclear magnetic resonance (NMR) measurements of water
      diffusion between and across bicellar lamellae were performed in positively and
      negatively magnetically aligned bicelles, composed of mixtures of DHPC (1,2
      dihexanoyl-sn-glycero-3-phosphocholine) and DMPC (1,2-dimyristoyl-sn-glycero-3
      phosphocholine), as a function of temperature and of the proportion of added
      short-chain lipid DHPC. (31)P NMR spectra obtained for each situation confirmed
      that the DHPC undergoes fast exchange between curved and planar regions as per
      the mixed bicelle model and permitted an estimate of the proportion of the two
      DHPC populations. Water diffusion across the bicellar lamellae was shown to scale
      directly with q*, the fraction of edge versus planar phospholipid, rather than
      simply the ratio q, the global fraction of long-chain to short-chain
      phospholipid. Geometric modeling of the dependence of water diffusion on q*
      suggested an upper limit of 400 A for the size of DHPC-rich toroidal perforations
      within the bicelle lamellae. These findings constitute an independent
      confirmation of the mixed bicelle model in which DHPC is not confined to edge
      regions but enjoys, instead, a finite miscibility with DMPC.

PMID- 19115875
TI  - Levitation-free vibrated droplets: resonant oscillations of liquid marbles.
AB  - A spherical conducting droplet in an alternating electric field is known to
      undergo shape oscillations. When the droplet is supported by a substrate, the
      shape is no longer a complete sphere, but shape resonances are still observed. To
      obtain a completely spherical droplet, some kind of levitation is needed, unless
      the droplet is in microgravity, and this has previously been provided by gas
      films or magnetic or other external forces. In this work, we report observations
      of shape oscillations of a hydrophobic-powder-coated droplet of water. A droplet
      of water rolled on a hydrophobic powder self-coats such that the water becomes
      encapsulated as a liquid marble. When the powder is a spherical hydrophobic grain
      with a contact angle greater than 90 degrees , it adheres to the solid-water
      interface with more than half of its diameter projecting from the liquid, thus
      ensuring the encapsulated water does not come into contact with any substrate.
      These liquid marbles are highly mobile and can be regarded as completely
      nonwetting droplets possessing contact angles of 180 degrees . In this work, we
      show that they also provide a new mechanism equivalent to levitating droplets and
      provide droplets with small contact areas and completely mobile contact lines for
      studies of shape oscillations. Liquid marbles were created using hydrophobic
      lycopodium and droplets of water containing potassium chloride and were excited
      into motion using an electrowetting-on-dielectric configuration with applied
      frequency swept from 1 to 250 Hz. Both an up-and-down motion and an oscillation
      involving multiple nodes were observed and recorded using a high-speed camera.
      The resonant oscillation modes of small liquid marbles were fitted to the theory
      for vibrations of a free spherical volume of fluid. This work demonstrates the
      principle that oscillation modes of completely nonwetting droplets can be studied
      using a simple powder coating approach without the need for an active mechanism
      for levitation.

PMID- 19115874
TI  - Temperature-triggered gelation of aqueous laponite dispersions containing a
      cationic poly(N-isopropyl acrylamide) graft copolymer.
AB  - In this work, temperature-triggered gelation of aqueous laponite dispersions
      containing a cationic poly(N-isopropylacrylamide) (PNIPAm) graft copolymer was
      investigated. The copolymer used was PDMA(+)(30)-g-(PNIPAm(210))(14) [Liu et al.
      Langmuir 2008, 24, 7099]. DMA(+) is quarternarized N,N-dimethylaminoethyl
      methacrylate. The presence of small concentrations of laponite enabled
      temperature-triggered gel formation to occur at low copolymer concentrations
      (e.g., 1 wt %). Dynamic rheological measurements of the gels showed that they had
      storage modulus values of up to 400 Pa when the total solid volume fraction
      (polymer and laponite) was only about 0.02. The storage modulus was dependent on
      both the temperature and the composition of the dispersion used for preparation.
      The key component that provided the temperature-triggered gels with their
      elasticity was found to be self-assembled nanocomposite (NC) sheets. These NC
      sheets spontaneously formed at room temperature upon addition of laponite to the
      copolymer solution. The NC sheets had lateral dimensions on the order of hundreds
      of micrometers and a thickness of a few micrometers. The NC sheets were present
      within the temperature-triggered gels and formed elastically effective chains.
      The NC sheets exhibited temperature-triggered contraction with a contraction
      onset temperature of 27 degrees C. A conceptual model is proposed to
      qualitatively explain the relationship between gel elasticity and dispersion
      composition.

PMID- 19115876
TI  - Photochromism of 7,4'-dihydroxyflavylium in an AOT reversed micelle system.
AB  - The investigation of a flavylium compound in AOT reverse micelles shows
      photochromic enhancement in a wide pH range, with features previously unobserved
      in other colloidal systems. In equilibrium, 7,4'-dihydroxyflavylium transforms
      into trans-chalcone species at pH above 2, but ion-pair formation of the
      flavylium species with the negatively charged AOT is observed until pH = 5. After
      irradiation, trans-chalcone species are transformed with high quantum yields into
      both flavylium and its quinoidal base (through cis-chalcone and hemiketal
      species) until pH equal to 9. While trans-chalcone is located at the hydrophobic
      side of the reverse micelle interface, flavylium species tend to solubilize in
      the water pool. Flash photolysis experiments probe essentially the trans-chalcone
      solubilization site, showing that photochromic conversion to flavylium species
      can be achieved without acid catalysis with a unimolecular rate constant of 0.22
      s(-1), while the slow recovery to equilibrium after irradiation probes
      essentially the water pool with a experimental pH-dependent rate constant. The
      photochromic mechanism is discussed, promising new insights about the possibility
      of changing the reversed micelle interfacial properties using photoresponsive
      addictives like flavylium compounds.

PMID- 19115877
TI  - Fabrication of gas nanosensors and microsensors via local anodic oxidation.
AB  - A nanosensor and microsensor fabrication method employing scanning probe
      microscopy (SPM) is demonstrated. Within such process, nano- or microscale metal
      oxide (MoO(x) or TiO(x)) structures, constituting the active region of a sensor,
      are directly fabricated onto a microscopic metal track via SPM-assisted local
      anodic oxidation (LAO). Two distinct LAO routes, a slow (conventional) or a fast
      (unusual) one, are employed to produce nano- and microsensors, which are tested
      at different temperatures using CO2 and H2 as test gases. Sensitivities down to
      ppm levels are demonstrated, and the possibility of easy integration into
      microfabrication processes is also discussed.

PMID- 19115878
TI  - Interfacial transduction of nucleic acid hybridization using immobilized quantum
      dots as donors in fluorescence resonance energy transfer.
AB  - Fluorescence resonance energy transfer (FRET) using immobilized quantum dots
      (QDs) as energy donors was explored as a transduction method for the detection of
      nucleic acid hybridization at an interface. This research was motivated by the
      success of the QD-FRET-based transduction of nucleic acid hybridization in
      solution-phase assays. This new work represents a fundamental step toward the
      assembly of a biosensor, where immobilization of the selective chemistry on a
      surface is desired. After immobilizing QD-probe oligonucleotide conjugates on
      optical fibers, a demonstration of the retention of selectivity was achieved by
      the introduction of acceptor (Cy3)-labeled single-stranded target
      oligonucleotides. Hybridization generated the proximity required for FRET, and
      the resulting fluorescence spectra provided an analytical signal proportional to
      the amount of target. This research provides an important framework for the
      future development of nucleic acid biosensors based on QDs and FRET. The most
      important findings of this work are that (1) a QD-FRET solid-phase hybridization
      assay is viable and (2) a passivating layer of denatured bovine serum albumin
      alleviates nonspecific adsorption, ultimately resulting in (3) the potential for
      a reusable assay format and mismatch discrimination. In this, the first
      incarnation of a solid-phase QD-FRET hybridization assay, the limit of detection
      was found to be 5 nM, and the dynamic range was almost 2 orders of magnitude.
      Selective discrimination of the target was shown using a three-base-pairs
      mismatch from a fully complementary sequence. Despite a gradual loss of signal,
      reuse of the optical fibers over multiple cycles of hybridization and
      dehybridization was possible. Directions for further improvement of the
      analytical performance by optimizing the design of the QD-probe oligonucleotide
      interface are identified.

PMID- 19115879
TI  - Molecular characterization of biomass burning aerosols using high-resolution mass
      spectrometry.
AB  - Chemical characterization of atmospheric aerosols presents a serious analytical
      challenge because of the complexity of particulate matter analyte composed of a
      large number of compounds with a wide range of molecular structures, physico
      chemical properties, and reactivity. In this study the chemical composition of
      the organic constituents of biomass burning aerosol (BBA) samples is
      characterized by high-resolution electrospray ionization mass spectrometry
      (ESI/MS). Accurate mass measurement combined with Kendrick analysis allows
      assignment of the elemental composition for hundreds of compounds in the range of
      m/z values of 50-1000. ESI/MS spectra of different BBA samples contain a variety
      of distinct, sample specific, characteristic peaks that can be used as unique
      markers for different types of biofuels. Our results indicate that a significant
      number of high-MW organic compounds in BBA samples are highly oxidized polar
      species that can be efficiently detected using ESI/MS but are difficult to
      observe using conventional gas-chromatography/mass spectrometry analysis of
      aerosol samples. More than 70% of the identified species have not been reported
      in the literature. Detected organic compounds show a clear increase in the degree
      of saturation as the molecular weight of the analyte molecules increases. The
      increase is particularly pronounced for the samples containing a large number of
      the CH(2)-based homologous series.

PMID- 19115880
TI  - Youthful exuberance.

PMID- 19115882
TI  - Clinical Scholars Program: providing palliative medicine education and training
      for physicians at eight sites.

PMID- 19115883
TI  - Number needed to harm.

PMID- 19115884
TI  - Palliative care in Jordan: culturally sensitive practice.

PMID- 19115885
TI  - Center to Advance Palliative Care palliative care consultation service metrics:
      consensus recommendations.
AB  - The need to standardize the prospective collection and analysis of data has been
      a cornerstone of education and technical assistance provided by the Center to
      Advance Palliative Care (CAPC). Data analysis is vital for strategic planning,
      quality improvement, and demonstration of program impact to hospital
      administrators, private funders, and policymakers. To develop a set of core
      measures, CAPC convened a consensus panel in 2008 to focus on the topic of
      operational metrics for consultation services. Operational metrics, as distinct
      from clinical, customer and financial metrics, describe the characteristics of
      patients seen on the consultation service, such as age, disease, location,
      referring service and disposition. The panel arrived at 12 metric domains, all
      but one of which can be used for either internal programmatic use or for external
      comparisons of service characteristics/impact between different hospitals. In an
      effort to ensure access to reliably high-quality palliative care data throughout
      the nation, hospital palliative care consultation teams are encouraged to collect
      and report outcomes for each of the twelve metric domains described here.

PMID- 19115886
TI  - The touch of empathy.

PMID- 19115887
TI  - Pediatric cancer deaths: curative or palliative?
AB  - AIMS: The aims of this study were to review the deaths of Malaysian pediatric
      oncology patients in order to determine the major causes and the proportion of
      patients who received palliative care. SUBJECTS AND METHODS: This was a
      retrospective review from 2001-2007 of deaths at the Pediatric Institute, General
      Hospital Kuala Lumpur. Clinical data such as age, gender, disease, cause, and
      place of death were collected. The patients were divided into two groups: those
      who received palliative care and those who received curative treatment. RESULTS:
      Two hundred forty-seven patients were included. There were 148 males and 99
      females. The age ranged from 2 months to 22 years (median, 4 years). One hundred
      thirty cases (53%) were still in the curative phase of treatment at the time of
      death. The most common cause of death was septicemia (62%), followed by
      hemorrhage (18%) and underlying cancer (14%). One hundred seventeen cases (47%)
      were in the palliative phase at the time of death. All palliative care deaths
      occurred in the oncology ward with one exception. CONCLUSION: Nearly half of all
      inpatient pediatric cancer deaths were palliative in nature. Septicemia and
      hemorrhage were the major causes of death in the others.

PMID- 19115888
TI  - Financial impact of palliative care consultation in a public hospital.
AB  - BACKGROUND: Palliative care programs assist with prognostication, symptom
      control, and communication with patient and family. Hospitals often require
      financial justification for new programs Objective: Study the financial impact of
      the palliative care consultation (PCc) service in a public hospital.
      SETTING/SUBJECTS: From January to December 2005, 258 deaths occurred on the
      medicine service. Of those deceased patients, 116 were studied. DESIGN: Inclusion
      criteria were 50 or more years of age, length of stay (LOS) 3 days or more,
      admission to an internal medicine service, and death during that hospitalization.
      MEASUREMENTS: Charges, diagnosis-related groups (DRGs), DRG weights, and
      demographic variables were examined. RESULTS: Of the 116 deceased patients
      studied, 61 patients received a PCc, while 55 did not. Most patients had Medicare
      or Medicaid (82.8%). Both groups were similar in terms of demographic
      characteristics. Average LOS was 14.4 days for patients with a PCc versus 12.2
      days for those without (p = 0.57). Median charges for the group without a PCc
      were $42,731, versus a median of $35,824 for those with a PCc. There was no
      significant variation of DRG weights within the same DRG. DRG weight was
      significantly positively correlated with charges. Both PCc and DRG weight were
      significant predictors of charges, with 36% of charges variability explained by
      PCc and DRG weight. CONCLUSIONS: PCc significantly reduced charges in adult
      patients who died during their last hospitalization, even though the average LOS
      was higher for those who received a PCc versus those who did not.

PMID- 19115889
TI  - How I wish to be remembered: the use of an advance care planning document in
      adolescent and young adult populations.
AB  - BACKGROUND: Discussing end-of-life (EOL) issues is difficult with any population.
      These conversations are even more challenging with adolescents and young adults
      due to the poignancy of the situation and the need for developmentally
      appropriate language. OBJECTIVE: To explore whether adolescents and young adults
      living with a life-limiting illness find it acceptable and helpful to have a
      planning document to share their wishes and thoughts regarding EOL care. If so,
      to learn about specific concerns adolescents and young adults feel are important
      to include in such a document. METHODS: Adolescents and young adults with
      metastatic cancer or pediatric human immunodeficiency virus (HIV)-1 infection
      were presented Five Wishes, an advance directive document for adults. Each
      participant was asked to critically evaluate each wish in terms of whether the
      concepts within were considered (1) appropriate to ask individuals the
      participant's age; (2) helpful for other people the participant's age to think
      about; (3) helpful to the participant to think about; (4) stressful to
      contemplate. Participants were also asked to suggest modifications and additions
      to the document. RESULTS: Twenty patients completed the survey. Ninety-five
      percent of the participants reported that an advance directive like Five Wishes
      would be "helpful" or "very helpful" to themselves, 90% stated that the document
      would be helpful to others, and no patients found talking about the issues in
      Five Wishes "stressful" or "very stressful." Participants were more interested in
      items concerning how they wanted to be treated and remembered than items
      concerning medical decision-making. CONCLUSIONS: An advance care planning
      document may be appropriate and helpful for adolescents and young adults living
      with a serious illness. Future research should further validate the preferences
      identified by participants and explore whether an age-appropriate document can
      improve communication with family and staff in EOL care.

PMID- 19115890
TI  - Evaluating a palliative care case management program for cancer patients: the
      Omega Life Program.
AB  - PURPOSE: This study evaluated a cancer case management pilot program focusing on
      palliative care, the Omega Life Program (OLP), by assessing whether the program
      was associated with reduced hospital utilization. METHODS: A retrospective
      observational study of patients with cancer who enrolled in the OLP
      (intervention) compared to those who chose not to enroll (comparison) from
      January 1, 2005 to February 28, 2007. Patients were included in the primary
      analyses if they died by the end of the study period and were enrolled in the
      program at least 1 week before death. Patients were followed from the time of
      referral until death. Outcomes included whether or not the patients had any
      admissions during this period and, for patients with at least one admission, the
      total number of inpatient hospital admissions, inpatient days, and hospital
      costs. RESULTS: Approximately 75% of eligible patients enrolled in the OLP; 60%
      were older than 50 and 60% were female. Of included patients in the intervention
      group (n = 69), 59% had no admissions compared to 15% of patients in the
      comparison group (n = 20). However, among patients who had at least one
      admission, the mean number of hospital admissions, inpatient days, and hospitals
      costs were not significantly different between the groups. CONCLUSIONS: In this
      pilot study, patients in the OLP had significantly reduced odds of having any
      hospital admissions compared to those in usual care. This type of program may
      improve outcomes for patients, but further research is needed to evaluate
      outcomes using larger samples and more rigorous study designs.

PMID- 19115892
TI  - Barriers to the best care of the dying in Queensland, Australia.
AB  - The process of dying for many Australians is not ideal. To improve the care of
      the dying in our community, the barriers preventing optimal care must be
      identified. Forty-two important barriers were identified by focus groups. Health
      care professionals (HCPs) working in palliative care (PC) throughout Queensland
      were asked to rate the importance of each of the barriers. Inadequate funding for
      PC, lack of after-hours care, insufficient medical support and the lack of HCPs
      in PC across several different settings were highlighted as the most important
      barriers. Uncertainty regarding death certification, society's difficulty in
      responding to cultural needs, patient fears that active treatment would be
      stopped and fear of palliative care were considered the least important barriers.
      Many HCPs seem concerned about issues they are less likely to influence. The
      results of this survey may be useful for future workforce planning.

PMID- 19115891
TI  - Intermittent subcutaneous opioids for the management of cancer pain.

PMID- 19115893
TI  - Communication dynamics in hospice teams: understanding the role of the chaplain
      in interdisciplinary team collaboration.
AB  - BACKGROUND: Hospice chaplains provide a specific expertise to patient and family
      care, however, individual roles and responsibilities that facilitate the
      interdisciplinary team environment are less well known. OBJECTIVE: The primary
      aim of this study was to investigate how hospice chaplains perceive their role in
      interdisciplinary team meetings and to what extent hospice chaplains share common
      experiences within the interdisciplinary team approach in hospice. METHOD:
      Hospice chaplains within a 10-state region participated in a 39-item phone survey
      about professional roles, group roles, and structural characteristics that
      influence their ability to participate in interdisciplinary collaboration.
      RESULTS: Findings revealed that professional role conflict is experienced,
      primarily with social workers. Informal group task and maintenance roles included
      team spiritual care advisor and conflict manager, and structural characteristics
      consisted of extracurricular communication outside of the organization.
      CONCLUSIONS: Although chaplains foster interdisciplinary collaboration within the
      hospice team, future research needs to address improvements to the chaplain's
      role within the interdisciplinary team process.

PMID- 19115894
TI  - Intracerebral hemorrhage for the palliative care provider: what you need to know.
AB  - Intracerebral hemorrhage (ICH) makes up 10%-30% of all strokes. Palliative care
      providers are often asked to get involved with ICH cases to aid with development
      of short-term and long-term goals. Prognosis can be calculated using the ICH
      score (based on Glasgow Coma Score score, ICH volume, presence of
      intraventricular hemorrhage, age, and location of origin) or the Essen score
      (based on age, NIH Stroke Scale [NIHSS], and level of consciousness). Do-not
      resuscitate (DNR) status is important to discuss with families. Expert consensus
      states DNR is appropriate if the patient has two of the following: severe stroke,
      life-threatening brain damage, or significant comorbidities. The process of
      withdrawing ventilatory support can differ greatly from that of a medical
      intensive care unit (ICU) patient. Most ICH patients die within 24 hours
      following extubation. Symptoms of dyspnea and pain warrant use of opioids before
      and after terminal extubation. In addition, treating death rattle and
      postextubation stridor are important interventions. Family meetings are a vital
      intervention to help explain prognosis, establish a plan of care, and to get all
      family members on the same page. Family meetings can have a rapid effect, with
      66% of families opting for withdrawal of life support to decide within 24 hours
      of such a meeting.

PMID- 19115895
TI  - Opioid allergic reactions #175.

PMID- 19115896
TI  - Hepatic encephalopathy in end-stage liver disease #188.

PMID- 19115897
TI  - Redefining medical success and failure.

PMID- 19115898
TI  - Radiation-induced second malignancies.
AB  - There have been significant improvements in cancer treatment in the last few
      decades. The use of radiation in the treatment of cancer is widespread and has
      increased. Up to 40% of cancer pts will receive radiotherapy as part of their
      management. More successful treatment has meant improved survival rates, but
      conversely patients are living longer and encountering more treatment-induced
      complications. The development of a second primary malignancy, often many years
      later, is one of the more sinister complications. The American National Cancer
      Institute published data in 2006 reporting that 'Cancer survivors constitute 3.5%
      of the US population' but that 'second malignancies among high risk groups now
      accounts for 16% of all cancer incidence. The timescale between completion of the
      radiotherapy and the development of a second malignancy, known as the latent
      period, can vary widely from as little as 5 years up to 50 years later. In this
      report we present three cases of radiation-induced second malignancies seen in
      the Palliative Care setting and then give an overview of radiation induced second
      malignancies, looking at the aetiology, genetics and the palliative care
      implications for these patients.

PMID- 19115909
TI  - Travel to high altitude with young children: an approach for clinicians.
AB  - As more families travel to mountainous destinations, clinicians are frequently
      asked for advice regarding children at altitude. We briefly review the principles
      of altitude illness in children, offer a management plan for the clinician, and
      highlight the gaps in current evidence. Planning for ascent, altitude illness
      management, and diagnostic follow-up are discussed.

PMID- 19115910
TI  - Hypoxemia and acute mountain sickness: which comes first?
AB  - Hypoxemia is usually associated with acute mountain sickness (AMS), but most
      studies have varied in time and magnitude of altitude exposure, exercise, diet,
      environmental conditions, and severity of pulmonary edema. We wished to determine
      whether hypoxemia occurred early in subjects who developed subsequent AMS while
      resting at a simulated altitude of 426 mmHg (approximately 16,000 ft or 4880 m).
      Exposures of 51 men and women were carried out for 8 to 12 h. AMS was determined
      by Lake Louise (LL) and AMS-C scores near the end of exposure, with spirometry
      and gas exchange measured the day before (C) and after 1 (A1), 6 (A6), and last
      (A12) h at simulated altitude and arterial blood at C, A1, and A12. Responses of
      16 subjects having the lowest AMS scores (nonAMS: mean LL=1.0, range=0-2.5) were
      compared with the 16 having the highest scores (+AMS: mean LL=7.4, range=5-11).
      Total and alveolar ventilation responses to altitude were not different between
      groups. +AMS had significantly lower PaO2 (4.6 mmHg) and SaO2 (4.8%) at A1 and
      3.3 mmHg and 3.1% at A12. Spirometry changes were similar at A1, but at A6 and
      A12 reduced vital capacity (VC) and increased breathing frequency suggested
      interstitial pulmonary edema in +AMS. The early hypoxemia in +AMS appears to be
      the result of diffusion impairment or venous admixture, perhaps due to a unique
      autonomic response affecting pulmonary perfusion. Early hypoxemia may be useful
      to predict AMS susceptibility.

PMID- 19115911
TI  - Intermittent hypoxic exposure does not improve sleep at 4300 m.
AB  - The purpose of this study was to determine in sea-level residents if 6 to 7
      consecutive days of normobaric intermittent hypoxic exposure (IHE) (hypoxia room:
      2-h ambient PO2=90 mmHg sedentary and 1-h ambient PO2=110 mmHg exercising at 80+/
      5% of maximum heart rate) improved sleep quality (awakenings per hour) and
      quantity at altitude (4300 m). We hypothesized that IHE would improve sleep
      arterial oxygen saturation (SaO2) levels and decrease desaturation events,
      thereby contributing to improvements in sleep quality and quantity during
      subsequent exposure to high altitude. Ten sea-level residents (mean+/-SE: 22+/-1
      yr, 179+/-2 cm, 79+/-3 kg) were assigned to an IHE group and six to a SHAM group
      (20+/-0.5 yr, 180+/-3 cm, 77+/-4 kg). Sleep quantity, SaO2, and heart rate (HR)
      were monitored at sea level and during high altitude (i.e., 4300 m in a hypobaric
      chamber) before pretest (PRE-T) and 60 h after posttest (POST-T) for the last IHE
      or SHAM treatment. Over the 6 to 7 days of IHE, resting SaO2 increased from 75+/
      1% to 81+/-3% in the IHE group, while the SHAM group remained at 98+/-1%. From
      PRE-T to POST-T at 4300-m exposure, both the IHE and SHAM groups had
      significantly higher sleep SaO2, fewer desaturation events per hour, and an
      increase in the percentage of time asleep while sleeping (sleep percent). The IHE
      group, but not the SHAM group, had significantly lower sleep HR and a trend to
      more awakenings during the POST-T 4300-m exposure. These results indicate that
      although IHE treatment induced significant ventilatory acclimatization, relative
      to the SHAM group, IHE did not further improve sleep SaO2 quality and quantity
      following rapid ascent to 4300 m. Rather, it is likely that the acquired
      ventilatory acclimatization was lost in the 60 h between the last IHE session and
      the POST-T altitude exposure.

PMID- 19115912
TI  - Prophylactic low-dose acetazolamide reduces the incidence and severity of acute
      mountain sickness.
AB  - Previous studies have shown low-dose acetazolamide to be effective in preventing
      AMS in persons already at high altitude and then moving higher, a relatively low
      risk situation. We wished to evaluate prophylactic administration of low-dose
      acetazolamide for reducing the incidence and severity of AMS in a high-risk
      setting: rapid ascent from 1600 to 4300 m. We performed a double-blind,
      randomized, placebo-controlled study with human subjects (n=44) exposed to 4300 m
      for 24 h. Subjects were treated for 3 days prior to ascent to 4300 m and during
      day 1 at altitude with placebo (n=22) or acetazolamide 250 mg/day (125 mg bid,
      n=22). AMS diagnosis required both an AMS-C score from the Environmental Symptom
      Questionnaire-III>or=0.7 and a Lake Louise Symptom (LLS) questionnaire score>or=3
      plus headache. Acetazolamide reduced the incidence of AMS compared to placebo
      treated subjects (14% vs. 45%, respectively, p=0.02), and the number needed to
      treat was 3. The AMS-C and LLS scores were lower in acetazolamide-treated
      subjects, indicating less severe AMS. Low-dose acetazolamide administered prior
      to ascent and on day 1 at 4300 m effectively reduced the incidence and severity
      of AMS in a high-risk setting.

PMID- 19115913
TI  - Pulmonary-artery pressure and exhaled nitric oxide in Bolivian and Caucasian high
      altitude dwellers.
AB  - There is evidence that high altitude populations may be better protected from
      hypoxic pulmonary hypertension than low altitude natives, but the underlying
      mechanism is incompletely understood. In Tibetans, increased pulmonary
      respiratory NO synthesis attenuates hypoxic pulmonary hypertension. It has been
      speculated that this mechanism may represent a generalized high altitude
      adaptation pattern, but direct evidence for this speculation is lacking. We
      therefore measured systolic pulmonary-artery pressure (Doppler chocardiography)
      and exhaled nitric oxide (NO) in 34 healthy, middle-aged Bolivian high altitude
      natives and in 34 age- and sex-matched, well-acclimatized Caucasian low altitude
      natives living at high altitude (3600 m). The mean+/-SD systolic right
      ventricular to right atrial pressure gradient (24.3+/-5.9 vs. 24.7+/-4.9 mmHg)
      and exhaled NO (19.2+/-7.2 vs. 22.5+/-9.5 ppb) were similar in Bolivians and
      Caucasians. There was no relationship between pulmonary-artery pressure and
      respiratory NO in the two groups. These findings provide no evidence that
      Bolivian high altitude natives are better protected from hypoxic pulmonary
      hypertension than Caucasian low altitude natives and suggest that attenuation of
      pulmonary hypertension by increased respiratory NO synthesis may not represent a
      universal adaptation pattern in highaltitude populations.

PMID- 19115914
TI  - Prevalence of acute mountain sickness among Finnish trekkers on Mount
      Kilimanjaro, Tanzania: an observational study.
AB  - The aim of this study was to evaluate the prevalence of acute mountain sickness
      (AMS) among trekkers on Mount Kilimanjaro during the winter season of 2006-2007.
      A A total of 130 Finnish trekkers at Marungu route were asked to complete daily a
      Lake Louise self-report and clinical assessment score questionnaire with the help
      of a trainee Finnish guide during their trek to Kilimanjaro. A Lake Louise
      questionnaire score>or=3 indicated AMS. Altogether 112 mountaineers or travelers
      [54 men, 58 women, mean age 51+/-10 (SD) years] were studied. Fifty-nine
      travelers (53%) reached Gillman's Point or Uhuru Peak. The incidence of AMS among
      Finnish Kilimanjaro trekkers was 75%. The most common high altitude symptoms were
      headache, followed by sleeping problems and fatigue or weakness. The incidence of
      AMS is high among trekkers climbing Mount Kilimanjaro.The main reason for this
      seems to be rapid ascent. Kilimanjaro treks normally have a fixed timetable, and
      for commercial reasons there is little opportunity to spend extra days for
      acclimatization in the camps. Some contributing factors are preventable, so we
      recommend an educational program for all the trekking agencies that guide on this
      peak and, in particular, the Tanzania-based guiding agencies, which, typically,
      are driving these very fast ascent rates.

PMID- 19115915
TI  - NT-proBNP does not rise on acute ascent to high altitude.
AB  - The response of brain natriuretic peptide (BNP) to acute ascent to altitude is of
      interest as a surrogate for ventricular function and because BNP is involved in
      the normal homeostasis of the pulmonary vasculature. The structurally related
      hormone atrial natriuretic pressure (ANP) has been demonstrated to be elevated at
      altitude and implicated in natriuresis. We measured plasma concentrations of ANP
      and NT-proBNP (a more stable BNP precursor) in 10 healthy non-HAPE-susceptible
      lowlanders during acute exposure to 5200 m on the Apex 2 expedition to Bolivia.
      Systolic pulmonary artery pressure (PASP) was measured using tricuspid
      regurgitant jet estimation by echocardiography. Despite a significant rise in the
      PASP, NT-proBNP did not rise. A small decrease in NT-pro BNP occurred after 7
      days at high altitude. There was no significant change in ANP levels. The lack of
      any increase in NT-proBNP in healthy resting subjects supports the view that
      ventricular function is well preserved and suggests that BNP is not playing a
      significant role in altered pulmonary artery pressure.

PMID- 19115916
TI  - Skeletal muscle adaptations to prolonged exposure to extreme altitude: a role of
      physical activity?
AB  - This study investigated skeletal muscle adaptations to high altitude and a
      possible role of physical activity levels. Biopsies were obtained from the m.
      quadriceps femoris (vastus) and m. biceps brachii (biceps) in 15 male subjects, 7
      active and 8 less active. Samples were obtained at sea level and after 75 days
      altitude exposure at 5250 m or higher. The muscle fiber size decreased at an
      average of 15% in the vastus and biceps, respectively, and to the same extent in
      both groups. In both muscles, the mean number of capillaries was 2.1-2.2
      cap.fiber(-1) before and after the exposure. As mean fiber area was reduced, the
      mean number of capillaries per unit area increased in all subjects (from 320 to
      405 cap/mm2) with no difference between the active and less active groups. The
      two enzymes selected to reflect mitochondrial capacity, citrate synthase (CS) and
      3-hydroxyl-CoA-dehydrogenase (HAD), did not change in the leg muscles with
      altitude exposure, CS: 28.7 (20.7-37.8) vs. 27.8 (23.8-29.4); HAD: 35.2 (20.3
      43.1) vs. 30.6 (20.7-39.7) micromol.min(-1).g(-1) d.w, pre- and post-altitude,
      respectively. The muscle buffer capacity was elevated in both the vastus; 220
      (194-240) vs. 232 (200-277) and the biceps muscles; 233 (190-301) vs. 253 (193
      320) after the acclimatization period. In conclusion, mean fiber area was reduced
      in response to altitude exposure regardless of physical activity which in turn
      meant that with an unaltered capillary to fiber ratio there was an elevation in
      capillaries per unit of muscle area. Muscle enzyme activity was unaffected with
      altitude exposure in both groups, whereas muscle buffer capacity was increased.

PMID- 19115917
TI  - Changes in pupil dynamics at high altitude--an observational study using a
      handheld pupillometer.
AB  - Gross pupil dynamics are used as an indirect measure of brain function. Changes
      in hypoxia and intracranial pressure are thought to alter pupil responses to
      light. This study assessed a portable handheld pupil measuring device
      (pupillometer) in the field investigating the changes in pupil size, speed of
      reaction, and rate of constriction/dilatation with hypoxia induced by changes in
      altitude. A correlation between pupil dynamics and acute mountain sickness was
      sought. Seventeen volunteers were studied following acute exposure to 3450 m and
      then during a trek to 4770 m in Ladakh, India. The pupillometer was used to
      record maximum and minimum pupil diameter in response to a standard light source
      with calculation of latency, constriction and dilatation velocities. Acute
      mountain sickness (AMS) was recorded using Lake Louise self completed
      questionnaires both in the morning and afternoon on each day. Acute altitude
      exposure resulted in a significant reduction of percentage change in pupil size
      (36.5% to 24.1% p=<0.001), significant delay in pupillary contraction (latency;
      0.208 to 0.223 seconds p=0.015) and a significant slowing of the rate of
      contraction (constriction velocity; -2.77 mm/s to -1.75 mm/s p=0.012). These
      changes reverted to normal during a period of acclimatization. A significant
      diurnal variation in pupil size was also observed. There was no significant
      difference between subjects with and without AMS. The handheld pupillometer is a
      suitable robust tool for monitoring changes in pupil dynamics in the field. With
      acute exposure to hypobaric hypoxia associated with an ascent to a moderate
      altitude, there is a general slowing of pupil function which reverts to normal
      within a few days of acclimatization. There appears to be a marked diurnal
      variation in pupil size. The measurements clearly demonstrated an effect of
      hypoxia on cerebral function, but these changes did not relate to moderate AMS.

PMID- 19115918
TI  - Prevalence of dry eye at high altitude: a case controlled comparative study.
AB  - High altitude is associated with physiological as well as pathological changes in
      the eye related to adverse environmental conditions that result in increased tear
      evaporation and contribute to a higher incidence of dry eye in these regions. We
      aimed to study the difference in prevalence of dry eye at high altitude and at
      low altitude. The prevalence of dry eye among the natives and the army soldiers
      who were recently posted at high altitude was also studied and compared. 200
      adults above 20 years of age were enrolled. 100 subjects were recruited at a high
      altitude region (study group), of which 50 were native Ladakhis and 50 were
      soldiers recently posted at Leh, Ladakh, India (height; 3300 m above sea level;
      temperature: 18 degrees C to 24 degrees C). 100 subjects, age and sex matched,
      were screened at a low altitude region, New Delhi, India (218 m above sea level;
      temperature: 19 degrees C to 24 degrees C) to serve as the control group.
      Prevalence of dry eye was assessed through standard questionnaires (McMonnies'
      Questionnaire (MMI), Ocular Surface Disease Index Questionnaire (OSDI), and
      Schirmer's basic secretion test. On the basis of the parameters studied
      (symptoms, MMI, OSDI and Schirmer's test), dry eye was diagnosed in 20% of
      subjects screened at high altitude and in 9% of subjects in the control group
      screened at low altitude. In the study group, the prevalence of dry eye was
      significantly higher amongst the native population (54%) than in the army
      soldiers who were recently posted at that region (26%). The difference was
      statistically significant (p<0.005). In conclusion, dry eye is more common at
      high altitude, particularly in the native population. Awareness among people
      residing at high altitude and the treating medical personnel needs to be created
      for early detection and treatment of dry eye to prevent vision-threatening
      complications.

PMID- 19115919
TI  - A short walk with Milledge.

PMID- 19115920
TI  - Altitude-related illness and retinal vascular geometry: a hypothesis.

PMID- 19115921
TI  - Do we have a best practice for treating high altitude pulmonary edema?

PMID- 19115922
TI  - Sensitivity of cerebral blood flow to hypoxia and hypoxic hypocapnia in Ethiopian
      highlanders.

PMID- 19115924
TI  - Low-dose acetylsalicylic Acid analog and acetazolamide for prevention of acute
      mountain sickness.

PMID- 19115926
TI  - Mechanism on polarity sorting of actin bundles formed with polycations.
AB  - In this paper we explored factors that determine the polarity of an Actin bundle
      formed with polycation through electrostatic interaction. We found that the
      polarity decreases with an increase in the polycation concentration while it
      hardly depends on the KCl salt concentration. Additionally, the polarity of the
      Actin bundle increases with an increase in the degree of polymerization of the
      polycation at a constant polymer concentration. From these results we proposed
      that the kinetics of nuclei formation determines the polarity of the Actin
      bundle.

PMID- 19115927
TI  - New synthesis of 3-fluoropyrroles.
AB  - 5-Alkoxymethyl-2-aryl-3-fluoro-1H-pyrroles and 2-aryl-3-fluoro-1H-pyrrole-5
      carbaldehydes were efficiently prepared from the corresponding 2-aryl-5
      (bromomethyl)-1-pyrrolines via electrophilic alpha,alpha-difluorination of the
      imino bond, using Selectfluor (1-chloromethyl-4-fluoro-1,4
      diazoniabicyclo[2.2.2]octane bistetrafluoroborate) and subsequent aromatization
      by dehydrofluorination. This methodology provides a new and easy entry toward
      various new 3-fluorinated pyrroles.

PMID- 19115928
TI  - Viral Immunology goes to a bimonthly format.

PMID- 19115929
TI  - Increase of pro-inflammatory cytokine expression in non-demyelinating early
      cerebral lesions in nervous canine distemper.
AB  - Canine distemper virus (CDV) infection of the central nervous system results in
      lesions of the gray and white matter. While a biphasic disease process has been
      discussed for leukoencephalitis with a prominent loss of viral protein
      expression, polioencephalitis has been associated with virus persistence. Using
      semi-quantitative reverse transcriptase polymerase chain reaction (RT-PCR),
      expression of pro- and anti-inflammatory cytokines such as interleukin (IL)
      1beta, IL-2, IL-6, IL-8, IL-10, IL-12, tumor necrosis factor-alpha (TNF)-alpha,
      interferon (IFN)-gamma, and transforming growth factor (TGF)-beta were studied in
      the cerebra of distemper dogs with white matter lesions in the cerebellum.
      Additionally, cytokine values were correlated with the degree of CDV infection,
      major histocompatibility complex class II (MHC II) expression, and infiltration
      of CD4-, CD8-, and CD3epsilon-positive lymphocytes. Cerebral CDV infection was
      not associated with detectable light microscopic lesions or infiltration of B and
      T lymphocytes. However, an increasing number of CDV-antigen-positive cells was
      associated with an upregulation of MHC II antigen. RT-PCR results revealed a
      significant upregulation of IL-6, IL-8, IL-12, and TNF-alpha in the cerebra of
      distemper dogs, whereas IL-10 and TGF-beta showed no significant increase.
      Elevated cytokine values were directly related to the presence of CDV antigen and
      MHC II upregulation. However, succeeding increases of the latter did not result
      in an additional proportional elevation of cytokine expression values. In
      summary, the present study demonstrates the expression of pro-inflammatory
      cytokines by resident neural cells following CDV infection. Furthermore, the lack
      of light microscopic changes indicates that additional factors besides cytokines
      are necessary for the development of a distemper-characteristic neuropathology.

PMID- 19115930
TI  - Cellular gene expression profiles in rhesus macaques challenged mucosally with a
      pathogenic R5 tropic simian human immunodeficiency virus isolate.
AB  - Insights into the host factors that contribute to an effective antiviral immune
      response may be obtained by examining global gene expression in simian human
      immunodeficiency virus (SHIV)-infected nonhuman primates that exhibit different
      virological outcomes. Immune responses and gene expression profiles in peripheral
      blood mononuclear cells (PBMCs) were compared between animals that controlled or
      did not control viremia after infection. Rectal inoculation of eight rhesus
      macaques with R5-tropic SHIV(SF162P3) resulted in a high level of plasma viremia
      during the acute phase of infection. The viremia was controlled to below levels
      of detection in six of these animals at the set point (controllers), whereas two
      animals had persistent viremia throughout the 140 wk that the animals were
      monitored (non-controllers). CD4(+) T-cell counts declined slightly in both
      controllers and non-controllers in the acute phase of infection, but CD4(+) T
      cell counts continued to decline only in the non-controllers. Neutralizing
      antibodies to the challenge virus were variable and could not account for the
      control of viremia. However, analysis of the cellular gene expression profiles in
      the PBMCs from both groups of animals revealed distinctive gene expression
      patterns between controllers and non-controllers. Using the paired LPE test, 59
      genes with p values <0.01 were identified and specific differences in the gene
      expression profiles in PBMCs from controllers versus non-controllers were
      detected.

PMID- 19115931
TI  - Unaltered neurological disease and mortality in CXCR3-deficient mice infected
      intracranially with lymphocytic choriomeningitis virus-Armstrong.
AB  - Intracranial infection of mice with lymphocytic choriomeningitis virus (LCMV)
      results in a lethal neurological disease termed lymphocytic choriomeningitis
      (LCM) that is mediated by antiviral CD8(+) T cells. Previous studies have
      implicated the chemokine receptor CXCR3 and its ligand CXCL10 in CD8(+) T cell
      trafficking in the brain and in the lethal disease following intracranial
      infection of mice with the LCMV-Traub strain. Here we investigated the role of
      CXCR3 in LCM following intracranial infection of mice with the LCMV-Armstrong
      strain. Significant induction of both CXCL9 and CXCL10 RNA and protein was seen
      in the central nervous system (CNS) in LCM. Cellular localization of the CXCL9
      and CXCL10 RNA transcripts was identified predominantly in infiltrating
      mononuclear cells, as well as in subpial and paraventricular microglia (CXCL9)
      and astrocytes (CXCL10). Despite a primary role of interferon (IFN)-gamma in
      inducing the expression of the CXCL9 gene, and to a lesser extent the CXCL10 gene
      in LCM, the absence of the IFN-gamma receptor did not influence the disease
      outcome. This finding suggested that these chemokines may not play a major role
      in the pathogenesis of LCM. To evaluate this possibility further the development
      of LCM was examined in mice that were deficient for CXCR3. Surprisingly, in the
      absence of CXCR3 there was no alteration in mortality, cytokine expression, or T
      cell infiltration in the CNS, demonstrating that in contrast to LCMV-Traub, CXCR3
      is not involved in the pathogenesis of LCMV-Armstrong-induced neurological
      disease in mice. Our findings indicate that despite similar immunopathogenetic
      mechanisms involving antiviral CD8(+) T cells, whether or not CXCR3 signaling has
      a role in LCM is dependent upon the infecting strain of LCMV.

PMID- 19115932
TI  - rAAV/Her-2/neu loading of dendritic cells for a potent cellular-mediated MHC
      class I restricted immune response against ovarian cancer.
AB  - Recent studies demonstrate that recombinant adeno-associated virus (rAAV)-based
      antigen loading of dendritic cells (DCs) generates, in vitro, significant and
      rapid cytotoxic T-lymphocyte (CTL) responses against viral antigens. We used the
      rAAV system to induce specific CTLs against tumor antigens for the development of
      ovarian cancer (OC) gene therapy. As an extension of the versatility of the rAAV
      system, we incorporated a self-antigen, Her-2/neu, which is expressed in many
      cancers, including breast and ovarian. We analyzed two different vectors
      containing a short (157-612) and long domain (1-1197). Our rAAV vector induced
      strong stimulation of CTLs directed against the self tumor antigen, Her-2/neu. We
      then investigated the efficiency of the CTLs in killing Her-2/neu-targeted cells.
      A significant MHC class I-restricted, anti-Her-2/neu-specific CTL killing was
      demonstrated against Her-2/neu-positive OC cells after one in vitro stimulation.
      In summary, single peripheral blood mononuclear cell (PBMC) stimulation with
      rAAV/157-612- or rAAV/1-1197-pulsed DCs induces strong antigen-specific CTL
      generation. The CTLs were capable of lysing low doses of peptides pulsed into
      target cells or OC Her-2/neu(+) tumors. These data suggest that AAV-based antigen
      loading of DCs is highly effective for generating human CTL responses against OC
      antigens.

PMID- 19115933
TI  - Humoral immune response against human bocavirus VP2 virus-like particles.
AB  - Human bocavirus (HBoV) was recently detected in samples from children and infants
      with infections of the respiratory tract. Here we analyze the prevalence of IgG
      and IgM antibodies against HBoV virus-like VP2 particles in healthy adult blood
      donors and children using a newly established standardized enzyme-linked
      immunosorbent assay. Virus-specific IgG antibodies were frequently detected in
      infants with active viremia and respiratory illness (10/24, 42%) and in young
      children without detectable HBoV genomes in their blood (27/52, 52%). In sera
      obtained from healthy adults, ubiquitous VP2-specific antibodies were found in
      280/299 (94%) cases. HBoV-specific IgM antibodies were detected in 10/24 (42%) of
      sera samples obtained from HBoV DNA-positive children, and in 6/24 (25%) the sera
      displayed equivocal responses. In contrast, VP2-specific IgM was not detectable
      in samples obtained from 52 children without detectable amounts of HBoV genomes
      in their blood. Only 2/299 sera samples from healthy adult blood donors were
      found to be IgM-positive (1%), and equivocal IgM responses were observed in 9/299
      (3%) individuals. In conclusion, a high IgG seroprevalence of HBoV in the adult
      population was observed, whereas the presence of virus-specific IgM was
      associated with viremia. These data show that ELISA test systems for the
      detection of HBoV-specific antibodies are a valuable tool for serological
      diagnosis of this new emerging pathogen.

PMID- 19115934
TI  - CpG used as an adjuvant for an adenovirus-based Venezuelan equine encephalitis
      virus vaccine increases the immune response to the vector, but not to the
      transgene product.
AB  - An adenovirus-based (ad-based) vaccine delivering antigens from the Alphavirus
      Venezuelan equine encephalitis virus (VEEV) is a strategy that offers clinical
      potential. A vaccine against VEEV is desirable because of the re-emerging nature
      of this virus, and also the potential that it may be used as a biological weapon.
      This study was designed to investigate whether the co-administration of CpG
      oligodeoxynucleotides (ODNs) with an ad-based VEEV vaccine could enhance the
      protective efficacy of the vaccine. We report that the co-administration of CpG
      ODN was unable to increase VEEV-specific antibody responses in mice, and was
      unable to increase the protective efficacy of the vaccine against aerosol
      challenge with virulent VEEV. However, it was noted that antibody responses
      directed against the adenovirus vaccine vector were increased, which may be
      detrimental, particularly in the context of homologous boosting.

PMID- 19115935
TI  - Co-immunization of mice with a retroviral DNA vaccine and GITRL-encoding plasmid
      augments vaccine-induced protection against retrovirus infection.
AB  - After more than 30 years of research a HIV vaccine is still not at hand. DNA
      vectors expressing viral antigens are very safe vaccines, but so far they have
      not been efficient enough to induced broad protective immunity against
      retroviruses. One strategy to enhance the efficiency of DNA vaccines is to
      augment effector T-cell priming against viral components by manipulating
      regulatory T-cell functions (Treg). Glucocorticoid-induced tumor necrosis factor
      receptor (GITR) is a molecule that is constitutively expressed on CD4(+) Treg
      cells, and antibodies or natural ligands binding this molecule can impair Treg
      cell suppression. Here we demonstrate using the retroviral Friend virus (FV)
      mouse model, that co-immunization of FV antigens along with GITR-ligand (GITRL)
      encoding plasmids protected mice efficiently against a FV challenge. On the other
      hand, treatment of DNA-vaccinated mice with alpha-GITR antibody did not improve
      vaccine-induced protection at all. Thus, for an effective priming of immunity
      against FV, GITRL and viral antigens might have to be expressed within the same
      local environment. The data suggest that limitations in DNA vaccination can be
      overcome by co-expressing co-stimulatory molecules that potentially manipulate
      the function of Treg cells during priming of anti-retroviral immunity.

PMID- 19115936
TI  - Complement component C1q and anti-hexon antibody mediate adenovirus infection of
      a CAR-negative cell line.
AB  - Realization of the potential clinical utility of recombinant adenovirus for gene
      therapy or vaccine development depends on a better understanding of the role of
      naturally occurring or therapy-induced anti-adenovirus antibodies. This study
      addresses the impact of anti-adenovirus neutralizing antibodies and the
      complement protein C1q on adenovirus infection of coxsackie and adenovirus
      receptor (CAR)-positive, and especially CAR-negative cells. Initially,
      transduction efficiency of adenovirus vectors was assessed in the presence or
      absence of human sera derived from healthy individuals that were seropositive for
      anti-adenovirus neutralizing antibodies. Infection was monitored by transgene
      expression in vitro using a replication-deficient adenovirus encoding green
      fluorescent protein (Ad-GFP). HeLa cells (CAR-positive) were readily infected by
      Ad-GFP and increasing concentrations of pooled sera increasingly inhibited
      infection. In contrast, rhabdomyosarcoma (RD) cells, a CAR-negative cell, were
      poorly infected by Ad-GFP. However, in the presence of human serum, robust GFP
      expression was observed. This expression was completely abrogated if the human
      serum was heat-inactivated. Addition of purified human C1q protein to the heat
      inactivated serum restored GFP expression. Similar results were seen when human
      C1q protein was added to purified anti-hexon antibodies, but not to anti-fiber or
      anti-penton base antibodies, thus implicating anti-hexon antibodies as the
      infective antibody component of the human sera. These studies suggest that
      complement protein C1q and anti-hexon antibodies together can mediate efficient
      adenovirus infection in CAR-negative cell types.

PMID- 19115937
TI  - HCMV IL-10 suppresses cytokine expression in monocytes through inhibition of
      nuclear factor-kappaB.
AB  - Modulation of host immune responses is a common strategy for promoting virus
      persistence and avoiding clearance. Human cytomegalovirus (HCMV) is known to
      encode numerous immunomodulatory genes, including a homolog of the cytokine human
      interleukin-10 (hIL-10). While having limited sequence homology to hIL-10,
      cytomegalovirus IL-10 (cmvIL-10) shares many functional characteristics with the
      human cytokine and acts as a potent suppressor of the inflammatory immune
      response. The mechanism by which hIL-10 inhibits inflammatory cytokines involves
      a transcriptional block via inhibition of nuclear factor-kappaB (NF-kappaB)
      activity. To determine whether cmvIL-10 employs the same mechanism to inhibit
      cytokine production, the effect of cmvIL-10 on NF-kappaB signaling in monocytes
      was investigated. The results demonstrate that cmvIL-10 does inhibit NF-kappaB
      activation, as evidenced by reduced degradation of the NF-kappaB inhibitor
      IkappaB-alpha, and decreased transcription of the NF-kappaB-responsive genes
      tumor necrosis factor-alpha (TNF-alpha) and IL-1beta. These studies confirm that
      cmvIL-10 mediates cytokine suppression by blocking NF-kappaB transcriptional
      activity in human monocytes.

PMID- 19115939
TI  - PTPN22 C1858T polymorphism and the outcome of hepatitis C virus infection.
AB  - The outcome of chronic hepatitis C virus infection varies, depending on viral and
      host factors. Those mechanisms involved in the control of the innate and adaptive
      response could have an influence on the outcome of infection. The PTPN22 gene
      encodes an intracellular lymphoid-specific phosphatase (Lyp) with a lymphocyte
      activating downregulatory effect. A single-nucleotide polymorphism (SNP) C1858T
      located on this gene has been associated with autoimmune diseases and bacterial
      infections. The aim of this study was to assess whether the PTPN22 C1858T
      polymorphism is related to the outcome of hepatitis C viral infection. A total of
      69 patients with spontaneous viral clearance (SVC), 281 patients with chronic
      hepatitis C (CHC), and 1036 individuals not infected with hepatitis C (NIC) were
      included in this study. Patients with CHC were stratified according to Scheuer
      score of hepatic fibrosis from F0-F2 (n = 200) and F3-F4 (n = 81), and according
      to their response to therapy in patients with sustained responses (SR; n = 103)
      and non-sustained response (NSR; n = 104). Genotyping of the C1858T polymorphism
      was performed using TaqMan probes. No statistically significant differences in
      the distribution of PTPN22 C1858T polymorphism were observed upon comparison of
      patient group with the NIC group. Also, when the different patient groups were
      compared to one another, no statistically significant differences were detected:
      the SVC with the CHC group (10.2% versus 12.5%; p = 0.6), the F0-F2 with the F3
      F4 group (11.5% versus 14.8%; p = 0.5), and the NSR with the SR group (11.5%
      versus 14.6%; p = 0.4). Our results do not support a major role of this
      polymorphism of the PTPN22 gene in the outcome of chronic hepatitis C virus
      infection in the Spanish population.

PMID- 19115940
TI  - Notice of retraction.

PMID- 19115938
TI  - Enhancement of mucosal and cellular immune response in mice by vaccination with
      respiratory syncytial virus DNA encapsulated with transfersome.
AB  - Respiratory syncytial virus (RSV) is one of the principal causes of bronchiolitis
      and pneumonia in young children, and currently there is no safe and effective
      vaccine. DNA vaccines encoding RSV surface glycoproteins are one option being
      examined. We evaluated the topical delivery of transfersome encapsulated DNA
      vaccine for its ability to confer protection against RSV challenge in mice and to
      determine whether such delivery could induce strong and specific immunity against
      RSV. After topical vaccination with a transfersome encapsulated RSV-F DNA, both
      RSV-specific mucosal antibody response and IFN-gamma-producing cells were
      detected. Intramuscular vaccination of naked RSV-F DNA only induced a significant
      anti-RSV IgG antibody response but no remarkable sIgA antibody and virus-specific
      cellular activity. Lungs from mice receiving topical vaccination had fewer
      histopathologic anomalies after RSV challenge than did mice receiving
      intramuscular vaccination or controls. Immunization with transfersome
      encapsulated F gene encoding DNA induces mucosal and cellular immune responses in
      mice that appear to produce protective immunity against respiratory syncytial
      virus.

PMID- 19115941
TI  - Sum-frequency spectroscopy of molecular adsorbates on low-index Ag surfaces:
      effects of azimuthal rotation.
AB  - Vibrational sum-frequency generation spectroscopy (SFG) lineshapes of p
      cyanobenzenethiol on low-index Ag crystal surfaces are studied as a function of
      azimuthal rotation by angle phi. A broadband multiplex SFG method is used, with a
      new technique that variably suppresses the non-resonant (NR) background using
      time-asymmetric time-delayed picosecond laser pulses. When both resonant (R) and
      NR signals are present, the amplitude and phase of the R line shape can vary
      significantly with phi, leading to dramatic phi-dependent variations of the SFG
      spectrum. The CN-stretch transition of p-cyanobenzenethiol modified Ag(111) and
      Ag(110) surfaces has an SFG spectrum consisting of a single vibrational resonance
      R atop a NR background that originates from the metal surface. Using the NR
      suppression technique, it was found that the R amplitude of the CN-stretch was
      independent of phi on both Ag(111) and Ag(110), which proves that the CN dipole
      moment is parallel to the surface normal in both cases. We show that it is
      possible to accurately extract the phi-dependence of the R amplitude, the NR
      amplitude, and the phase difference from SFG spectra by suppressing the NR signal
      during sample roation, thereby proving that the R contribution from the CN
      stretch transition evidence phi-invariant behavior on both Ag surfaces.

PMID- 19115942
TI  - Charge transport behavior of N-(2-Mercaptopropionyl glycine)-protected gold
      clusters with temperature.
AB  - N-(2-Mercaptopropionyl glycine)-passivated gold clusters (Au-MPG) represent a
      unique networked system of monolayer-protected clusters (MPCs) due to inter-
      and/or intramolecular hydrogen bonding between the MPC units thanks to the
      terminal carboxylic acid groups of the monolayers. We have investigated the size
      dependent electric charge transport in well-dried thin films of Au-MPG MPCs by a
      four-probe methodology as a function of temperature. The MPCs display a novel
      behavior of metallic-like-to-semiconductor crossover with increase of
      temperature. The MPCs having average cluster core sizes of approximately 1.6,
      approximately 3, and approximately 4 nm displayed a metallic-like nature (a
      linear increase of resistance of the films with increase of temperature) at low
      temperatures ( approximately 20-60 K), which crosses over to semiconductor
      behavior (decrease of resistance with increase of temperature) at high
      temperatures.

PMID- 19115943
TI  - Designed alpha-helical tectons for constructing multicomponent synthetic
      biological systems.
AB  - One possible route to develop new synthetic-biological systems is to assemble
      discrete nanoscale objects from programmed peptide-based building blocks. We
      describe an algorithm to design such blocks based on the coiled-coil protein
      folding motif. The success of the algorithm is demonstrated by the production of
      six peptides that form three target parallel, blunted-ended heterodimers in
      preference to any of the other promiscuous pairings and alternate configurations,
      for example, homodimers, sticky-ended assemblies, and antiparallel arrangements.
      The peptides were linked to promote the assembly of larger, defined nanoscale
      rods, thus demonstrating that targeted peptide-peptide interactions can be
      specified in complex mixtures.

PMID- 19115944
TI  - Nucleobase mediated, photocatalytic vesicle formation from an ester precursor.
AB  - We report the use of photoinduced electron transfer to drive reductive cleavage
      of an ester to produce bilayer-forming molecules; specifically, visible
      photolysis in a mixture of a decanoic acid ester precursor, hydrogen donor
      molecules, and a ruthenium-based photocatalyst that employs a linked nucleobase
      (8-oxo-guanine) as an electron donor generates decanoic acid. The overall
      transformation of the ester precursor to yield vesicles represents the use of an
      external energy source to convert nonstructure forming molecules into amphiphiles
      that spontaneously assemble into vesicles. The core of our chemical reaction
      system uses an 8-oxo-G-Ru photocatalyst, a derivative of [tris(2,2'-bipyridine)
      Ru(II)](2+).

PMID- 19115945
TI  - Single-molecule observation of photocatalytic reaction in TiO2 nanotube:
      importance of molecular transport through porous structures.
AB  - We have investigated the photocatalytic activity of individual porous TiO(2)
      nanotubes by the single-molecule counting of (*)OH using a specific fluorescent
      probe. The time- and space-resolved observation of emissive fluorescein generated
      by the photocatalytic reaction clearly reveals the importance of the transport
      behavior of reagents through the porous structures on the photocatalytic activity
      and the existence of the spatial heterogeneity of reactive sites even in an
      isolated TiO(2) nanotube. An experiment on a single nanotube provided information
      that was useful for elucidating the reaction mechanism of the heterogeneous
      (photo)catalyst and for designing advanced porous materials.

PMID- 19115946
TI  - Are carboxyl groups the most acidic sites in amino acids? Gas-phase acidities,
      photoelectron spectra, and computations on tyrosine, p-hydroxybenzoic acid, and
      their conjugate bases.
AB  - Deprotonation of tyrosine in the gas phase was found to occur preferentially at
      the phenolic site, and the conjugate base consists of a 70:30 mixture of
      phenoxide and carboxylate anions at equilibrium. This result was established by
      developing a chemical probe for differentiating these two isomers, and the
      presence of both ions was confirmed by photoelectron spectroscopy. Equilibrium
      acidity measurements on tyrosine indicated that deltaG(acid)(o) = 332.5 +/- 1.5
      kcal mol(-1) and deltaH(acid)(o) = 340.7 +/- 1.5 kcal mol(-1). Photoelectron
      spectra yielded adiabatic electron detachment energies of 2.70 +/- 0.05 and 3.55
      +/- 0.10 eV for the phenoxide and carboxylate anions, respectively. The H/D
      exchange behavior of deprotonated tyrosine was examined using three different
      alcohols (CF3CH2OD, C6H5CH2OD, and CH3CH2OD), and incorporation of up to three
      deuterium atoms was observed. Two pathways are proposed to account for these
      results, and all of the experimental findings are supplemented with B3LYP/aug-cc
      pVDZ and G3B3 calculations. In addition, it was found that electrospray
      ionization of tyrosine from a 3:1 (v/v) CH3OH/H2O solution using a commercial
      source produces a deprotonated [M-H]- anion with the gas-phase equilibrium
      composition rather than the structure of the ion that exists in aqueous media.
      Electrospray ionization from acetonitrile, however, leads largely to the liquid
      phase (carboxylate) structure. A control molecule, p-hydroxybenzoic acid, was
      found to behave in a similar manner. Thus, the electrospray conditions that are
      employed for the analysis of a compound can alter the isomeric composition of the
      resulting anion.

PMID- 19115947
TI  - The CN7(-) anion.
AB  - Several salts containing the CN7(-) anion were prepared by deprotonation of 5
      azido-1H-tetrazole (1). The highly explosive compounds hydrazinium (2), ammonium
      (3), aminoguanidinium (4), guanidinium (5), lithium (6), sodium (7), potassium
      (8), cesium (9), and calcium (10) azidotetrazolate were characterized by low
      temperature single X-ray diffraction. Other analytic methods, such as IR and
      Raman spectroscopy, multinuclear NMR spectroscopy, mass spectrometry, and
      differential scanning calorimetry were performed when possible since some of the
      metal salts explode spontaneously. 2 contains the highest nitrogen content
      (87.48%) of all known tetrazole salts. The impact, friction, and electrical spark
      sensitivity of 2, 3, 4, and 5 were measured, resulting in values which belong to
      primary explosives. In addition, the heats of formation of 2, 3, and 4 were
      calculated using the CBS-4M level of quantum mechanical theory. These, in turn,
      were used to estimate detonation pressure p(C-J) and velocity D(det) as well as
      the specific impulse I(sp).

PMID- 19115948
TI  - The crystal structure of an avian IgY-Fc fragment reveals conservation with both
      mammalian IgG and IgE.
AB  - Avian IgY is closely related to an ancestor of both mammalian IgG and IgE and
      thus provides insights into the evolution of antibody structure and function. A
      recombinant fragment of IgY-Fc consisting of a dimer of the Cupsilon3 and
      Cupsilon4 domains, Fcupsilon3-4, was expressed and crystallized and its X-ray
      structure determined to 1.75 A resolution. Fcupsilon3-4 is the only nonmammalian
      Fc fragment structure determined to date and provides the first structural
      evidence for an ancient origin of antibody architecture. The Fcupsilon3-4
      structure reveals features common to both IgE-Fc and IgG-Fc, and the implications
      for IgY binding to its receptor are discussed.

PMID- 19115949
TI  - Genomewide association study of an AIDS-nonprogression cohort emphasizes the role
      played by HLA genes (ANRS Genomewide Association Study 02).
AB  - To elucidate the genetic factors predisposing to AIDS progression, we analyzed a
      unique cohort of 275 human immunodeficiency virus (HIV) type 1-seropositive
      nonprogressor patients in relation to a control group of 1352 seronegative
      individuals in a genomewide association study (GWAS). The strongest association
      was obtained for HCP5 rs2395029 (P=6.79x10(-10); odds ratio, 3.47) and was
      possibly linked to an effect of sex. Interestingly, this single-nucleotide
      polymorphism (SNP) was in high linkage disequilibrium with HLA-B, MICB, TNF, and
      several other HLA locus SNPs and haplotypes. A meta-analysis of our genomic data
      combined with data from the previously conducted Euro-CHAVI (Center for HIV/AIDS
      Vaccine Immunology) GWAS confirmed the HCP5 signal (P=3.02x10(-19)) and
      identified several new associations, all of them involving HLA genes: MICB, TNF,
      RDBP, BAT1-5, PSORS1C1, and HLA-C. Finally, stratification by HCP5 rs2395029
      genotypes emphasized an independent role for ZNRD1, also in the HLA locus, and
      this finding was confirmed by experimental data. The present study, the first
      GWAS of HIV-1 nonprogressors, underscores the potential for some HLA genes to
      control disease progression soon after infection.

PMID- 19115950
TI  - Pathogenesis of staphylococcal infection: a manner of expression.

PMID- 19115951
TI  - Virulence gene expression in human community-acquired Staphylococcus aureus
      infection.
AB  - Isolates of methicillin-resistant Staphylococcus aureus (MRSA) were once linked
      uniformly with hospital-associated infections; however, community-acquired MRSA
      (CA-MRSA) now represents an emerging threat worldwide. To examine the association
      of differential virulence gene expression with outcomes of human infection, we
      measured transcript levels of target staphylococcal genes directly in clinical
      samples from children with active known or suspected CA-MRSA infections.
      Virulence genes encoding secreted toxins, including Panton-Valentine leukocidin,
      were highly expressed during superficial and invasive CA-MRSA infections. In
      contrast, increased expression of surface-associated protein A was linked only
      with invasive disease. Comparisons with laboratory-grown corresponding clinical
      isolates revealed that tissue-specific expression profiles reflect the activity
      of the staphylococcal accessory gene regulator during human infection. These
      results represent the first demonstration of staphylococcal gene expression and
      regulation directly in human tissue. Such analysis will help to unravel the
      complex interactions between CA-MRSA and its host environmental niches during
      disease development.

PMID- 19115952
TI  - Targeted metabolite analysis and biological activity of Pieris brassicae fed with
      Brassica rapa var. rapa.
AB  - For the first time, an insect-plant system, Pieris brassicae fed with Brassica
      rapa var. rapa, was tested for its biological capacity, namely, antioxidant
      (DPPH*, *NO, and O(2)*- radicals) and antimicrobial (bacteria and fungi)
      activities. Samples from the insect's life cycle (larvae, excrements, exuviae,
      and butterfly) were always found to be more efficient than the host plant. Also,
      P. brassicae materials, as well as its host plant, were screened for phenolics
      and organic acids. The host plant revealed higher amounts of both compounds. Two
      phenolic acids, ferulic and sinapic, as well as kaempferol 3-Osophoroside, were
      common to insect (larvae and excrements) and plant materials, with excrements
      being considerably richer. Detection of sulfated compounds in excrements, absent
      in host plant, revealed that metabolic processes in this species involved
      sulfation. Additionally, deacylation and deglycosilation were observed. All
      matrices presented the same organic acids qualitative profile, with the exception
      of excrements.

PMID- 19115954
TI  - Development of animal models and sandwich-ELISA tests to detect the allergenicity
      and antigenicity of fining agent residues in wines.
AB  - Food allergy can cause food-related anaphylaxis. Food allergen labeling is the
      principal means of protecting sensitized individuals. This motivated European
      Directive 2003/89 on the labeling of ingredients or additives that could trigger
      adverse reactions, which has been in effect since 2005. During this study, we
      developed animal models with allergy to ovalbumin, caseinate, and isinglass in
      order to be able to detect fining agent residues that could induce anaphylactic
      reactions in sensitized mice. The second aim of the study was to design sandwich
      ELISA tests specific to each fining agent in order to detect their residue
      antigenicity, both during wine processing and in commercially available bottled
      wines. Sensitized mice and sandwich ELISA methods were established to test a vast
      panel of wines. The results showed that although they were positive to our highly
      sensitive sandwich-ELISA tests, some commercially available wines are not
      allergenic in sensitized mice. Commercially available bottled wines made using
      standardized processes, fining, maturation, and filtration, do not therefore
      represent any risk of anaphylactic reactions in sensitized mice.

PMID- 19115955
TI  - Effect of xanthan on the molecular mobility of amorphous sucrose detected by
      erythrosin B phosphorescence.
AB  - Molecular mobility in amorphous solids is modulated by composition and
      environmental conditions such as temperature. Phosphorescence of erythrosin B was
      used to generate a mobility map of amorphous sucrose film doped with xanthan gum
      at weight ratios of xanthan/sucrose ranging from 0.0001 to 0.01. On the basis of
      analysis of the emission energy and lifetime of erythrosin B in pure sucrose and
      sucrose-xanthan films over the temperature range from 5 to 100 degrees C, we
      conclude that xanthan influences the molecular mobility as well as the dynamic
      site heterogeneity of amorphous sucrose in a dose-dependent fashion. At
      xanthan/sucrose weight ratios below approximately 0.0005, both emission energy
      and lifetime decreased and k(TS0) (the nonradiative decay rate of the triplet
      state) increased, indicating that xanthan increased the matrix molecular
      mobility. At weight ratios above 0.001, both emission energy and lifetime
      increased and k(TS0) decreased, indicating that xanthan decreased matrix
      mobility, reaching a plateau at weight ratios between 0.005 and 0.01. The
      concentration at which the effect of xanthan switched from increasing to
      decreasing mobility was similar to the concentration at which polymer chains
      overlapped in solution, suggesting that the dynamic changeover reflected the
      onset of chain overlap in the amorphous solid. Systematic trends in the emission
      bandwidth and lifetime heterogeneity and variations in the emission lifetime vs
      wavelength indicated that xanthan reduced the matrix dynamic site heterogeneity
      except at a weight ratio of 0.01. These data illustrate the complex effects of a
      polymer with a rigid structure and large side chains on the mobility of an
      amorphous, hydrogen-bonded sugar matrix.

PMID- 19115956
TI  - Synthesis, transport and pharmacokinetics of 5'-amino acid ester prodrugs of 1
      beta-D-arabinofuranosylcytosine.
AB  - Cytarabine (1-beta-d-arabinofuranosylcytosine, ara-C, 1) suffers from low oral
      bioavailability due to low intestinal membrane permeability and poor metabolic
      stability, and intravenous infusion is usually adopted as the clinical standard
      dosing administration. To develop an oral alternative for 1 and utilize the
      intestinal oligopeptide transporter 1 (PepT1), a series of 5'-amino acid ester
      derivatives of 1 was synthesized to clarify which modification was the most
      suitable to increase the oral bioavailability of 1. Their apical-to-basolateral
      permeability across Caco-2 cells and the antiproliferative activity with HL-60
      cells were screened. 5'-Valyl prodrug 2 demonstrated the highest permeability and
      was selected for further study. Glycylsarcosine (gly-sar, a typical substrate of
      PepT1) uptake by Caco-2 cells can be inhibited by 2 in a concentration-dependent
      manner, and IC(50) for 2 was 2.18 +/- 0.12 mM. The uptake of 2 was markedly
      increased in the long-term leptin-treated Caco-2 cells compared with the control
      Caco-2 cells, and was significantly inhibited by the excess of gly-sar, but not
      by l-valine. A dose-proportional pharmacokinetics was observed in rats when 5,
      15, 30 mg/kg doses of 2 (calculated as 1) were orally administered. The oral
      absolute bioavailability of 1 was 60.0% and 21.8% after 2 and 1 were orally
      administered to rats 30 mg/kg, respectively. Following oral administration of 15
      mg/kg, the absorption and bioactivation of 2 were extensive and rapid, over 98%
      of prodrug hydrolysis occurring before appearance in the portal vein. The in vivo
      dispositions of 1-beta-D-arabinofuranosyluracil (ara-U), a deaminated product of
      1, were investigated. Oral administration of 2 resulted in an increased 1/ara-U
      ratio (2.76) in the blood, much higher than that (1.25) after 1 orally taken.
      Overall, these results demonstrated that the PepT1-mediated absorption of 2 and
      the increased metabolic stability resulted in a dramatic increase in the oral
      bioavailability of 1 in rats and further corroborated the thought that prodrug
      design strategy targeting intestinal PepT1 was an important and promising
      strategy to improve oral bioavailability of poorly absorbed drugs.

PMID- 19115958
TI  - Observation of molecular ions and analysis of nonpolar compounds with the direct
      analysis in real time ion source.
AB  - Positive ions in the direct analysis in real time (DART) ion source are commonly
      formed by proton transfer. However, the DART source is similar to atmospheric
      pressure photoionization (APPI) in that it can produce molecular ions as well as
      protonated molecules, although the two sources differ in the initial ion
      formation process. This report discusses some of the factors that influence
      molecular ion formation in DART and shows how the DART source can be used to
      analyze "difficult" or nonpolar compounds such as alkanes and cholesterol. Trace
      reagent ions including NO(+) and O(2)(+)* formed from atmospheric gases are shown
      to play important roles in DART ionization. The use of the DART source as a gas
      chromatography/mass spectrometry (GC/MS) interface is demonstrated to show the
      difference between mass spectra obtained using conditions that favor proton
      transfer and those that favor molecular ion formation.

PMID- 19115957
TI  - Nonviral methods for siRNA delivery.
AB  - RNA interference (RNAi) as a mechanism to selectively degrade mRNA (mRNA)
      expression has emerged as a potential novel approach for drug target validation
      and the study of functional genomics. Small interfering RNAs (siRNA) therapeutics
      has developed rapidly and already there are clinical trials ongoing or planned.
      Although other challenges remain, delivery strategies for siRNA become the main
      hurdle that must be resolved prior to the full-scale clinical development of
      siRNA therapeutics. This review provides an overview of the current delivery
      strategies for synthetic siRNA, focusing on the targeted, self-assembled
      nanoparticles which show potential to become a useful and efficient tool in
      cancer therapy.

PMID- 19115959
TI  - Method for the accurate preparation of cell-spiking standards.
AB  - Preparation of calibration standards for cell enumeration is critical in
      characterizing the performance of any method or apparatus intended for recovering
      rare cells. Diluting a cell suspension serially is prone to statistical sampling
      errors as the cell suspension becomes more dilute, whereas transferring and
      injecting cells individually into a diluent with a micromanipulator is time
      consuming. We developed a simple and robust method using a surface-modified glass
      capillary to siphon and eject cells. One-dimensional confinement of cells offered
      by the capillary made cell enumeration by visual counting simple and rapid, and
      cell ejection from the capillary was near 100% when the appropriate surface
      coating and cell solution was used. The residence time of cells in the capillary,
      however, could affect the percentage of cells that was ejected from the
      capillary. To characterize the performance of this method, we enumerated the
      ejected cell using both visual counting under a microscope and automated
      detection using a chip-based flow cytometer.

PMID- 19115960
TI  - Generation of a calmodulin-based EPR calcium indicator.
AB  - Calmodulin is a ubiquitous calcium dependent protein. In the presence of calcium,
      calmodulin adopts an altered conformation that leads to the generation of
      downstream cellular calcium signals. Here we describe the introduction of
      nitroxide EPR probes into calmodulin by means of site-directed spin labeling.
      These probes sense the calcium-dependent conformational change of calmodulin and,
      therefore, can serve as calcium indicators. In combination with a light-sensitive
      calcium chelator, spin-labeled calmodulin can be used to demonstrate calcium
      release by flash photolysis. These results provide an important step toward
      describing the molecular dynamics of calcium-induced conformational changes in
      proteins using EPR spectroscopy.

PMID- 19115961
TI  - Stabilization of Torpedo californica acetylcholinesterase by reversible
      inhibitors.
AB  - The dimeric form of Torpedo californica acetylcholinesterase provides a valuable
      experimental system for studying transitions between native, partially unfolded,
      and unfolded states since long-lived partially unfolded states can be generated
      by chemical modification of a nonconserved buried cysteine residue, Cys 231, by
      denaturing agents, by oxidative stress, and by thermal inactivation. Elucidation
      of the 3D structures of complexes of Torpedo californica acetylcholinesterase
      with a repertoire of reversible inhibitors permits their classification into
      three categories: (a) active-site directed inhibitors, which interact with the
      catalytic anionic subsite, at the bottom of the active-site gorge, such as
      edrophonium and tacrine; (b) peripheral anionic site inhibitors, which interact
      with a site at the entrance to the gorge, such as propidium and d-tubocurarine;
      and (c) elongated gorge-spanning inhibitors, which bridge the two sites, such as
      BW284c51 and decamethonium. The effects of these three categories of reversible
      inhibitors on the stability of Torpedo californica acetylcholinesterase were
      investigated using spectroscopic techniques and differential scanning
      calorimetry. Thermodynamic parameters obtained calorimetrically permitted
      quantitative comparison of the effects of the inhibitors on the enzyme's thermal
      stability. Peripheral site inhibitors had a relatively small effect, while gorge
      spanning ligands and those binding at the catalytic anionic site, had a much
      larger stabilizing effect. The strongest effect was, however, observed with the
      polypeptide toxin, fasciculin II (FasII), even though, in terms of its binding
      site, it belongs to the category of peripheral site ligands. The stabilizing
      effect of the ligands binding at the anionic subsite of the active site, like
      that of the gorge-spanning ligands, may be ascribed to their capacity to
      stabilize the interaction between the two subdomains of the enzyme. The effect of
      fasciculin II may be ascribed to the large surface area of interaction (>2000
      A(2)) between the two proteins. Stabilization of Torpedo californica
      acetylcholinesterase by both divalent cations and chemical chaperones was earlier
      shown to be due to a shift in equilibrium between the native state and a
      partially unfolded state ( Millard et al. ( 2003 ) Protein Sci. 12 , 2337 - 2347
      ). The low molecular weight inhibitors used in the present study may act
      similarly and can thus be considered as pharmacological chaperones for
      stabilizing the fully folded native form of the enzyme.

PMID- 19115962
TI  - Making sense of a missense mutation: characterization of MutT2, a Nudix hydrolase
      from Mycobacterium tuberculosis, and the G58R mutant encoded in W-Beijing strains
      of M. tuberculosis.
AB  - Recent polymorphism analyses of Mycobacterium tuberculosis strains have
      identified missense mutations unique to the W-Beijing lineage in genes belonging
      to the Nudix hydrolase superfamily. This study investigates the structure and
      function of one of these Nudix hydrolases, MutT2, and examines the effect that
      the W-Beijing mutation (G58R) has on enzyme characteristics. MutT2 has a
      preference for cytidine triphosphates, and although the G58R mutation does not
      alter nucleotide specificity, it reduces the protein's affinity for divalent
      cations. The K(D) of free Mg(2+) is 79-fold higher for the G58R mutant (3.30 +/-
      0.19 mM) compared with that for the wild-type (41.7 +/- 1.4 microM). Circular
      dichroism and nuclear magnetic resonance spectroscopy measurements show that
      while the mutation does not perturb the overall structure of the protein, protein
      stability is significantly compromised by the presence of the arginine with
      DeltaG (H(2)O), the free-energy of unfolding, being reduced by 2.48 kcal mol(-1)
      in the G58R mutant. Homology modeling of MutT2 shows that Gly-58 is in close
      proximity (10.8 A) to the Mg(2+) binding site formed by the highly conserved
      Nudix box residues and hydrogen bonds with Ala-54 in the preceding alpha-helix.
      This may explain the increased divalent cation requirement and decreased
      stability observed when an arginine is substituted for glycine at this position.
      A role for MutT2 in the regulation of cytidine-triphosphates available for
      nucleotide-dependent reactions is postulated, and the impact that the G58R
      mutation may have on these reactions is discussed.

PMID- 19115963
TI  - Influence of the hydric environment on water exchange and hatchlings of rigid
      shelled turtle eggs.
AB  - To examine the possible influence of incubation substrate water potential on
      rigid-shelled chelonian eggs and hatchlings, rigid-shelled eggs from four
      clutches of Brisbane River turtle (Emydura signata) were incubated buried in
      vermiculite at water potentials of approximately -100, -350, and -850 kPa, and
      patterns of egg mass change and hatchling attributes were examined. All eggs
      hatched successfully, and there was no apparent effect of water potential on
      incubation period, fresh hatchling mass, hatchling water content, or hatchling
      size. Clutch of origin also had no apparent effect on these attributes when
      initial egg mass was used as a covariate. However, clutch of origin affected
      initial egg mass, and clutch of origin and incubation water potential influenced
      the amount of water exchanged between the eggs and their environment during
      incubation and the amount of residual yolk found in hatchlings. Substrate water
      potential has little effect on hatchling outcomes other than the proportion of
      yolk converted to hatchling tissue during incubation in the rigid-shelled eggs of
      E. signata. It would appear that in general, the substrate water potential during
      incubation affects the quality of chelonian hatchlings by influencing the amount
      of yolk converted to hatchling tissue during embryonic development and that this
      influence is stronger in flexible-shelled eggs than in rigid-shelled eggs.

PMID- 19115964
TI  - Electrogenerated chemiluminescence from PbS quantum dots.
AB  - We report the first observation of electrogenerated chemiluminescence (ECL) from
      PbS quantum dots (QDs). Different ECL intensities are observed for different
      ligands used to passivate the QDs, which indicates that ECL is sensitive to
      surface chemistry, with the potential to serve as a powerful probe of surface
      states and charge transfer dynamics in QDs. In particular, passivation of the QD
      surfaces with trioctylphosphine (TOP) increases ECL intensity by 3 orders of
      magnitude when compared to passivation with oleic acid alone. The observed
      overlap of the ECL and photoluminescence spectra suggests a significant reduction
      of deep surface trap states from the QDs passivated with TOP.

PMID- 19115965
TI  - Metabolism and aging: effects of cold exposure on metabolic rate, body
      composition, and longevity in mice.
AB  - The proposition that increased energy expenditure shortens life has a long
      history. The rate-of-living theory (Pearl 1928 ) states that life span and
      average mass-specific metabolic rate are inversely proportional. Originally based
      on interspecific allometric comparisons between species of mammals, the theory
      was later rejected on the basis of comparisons between taxa (e.g., birds have
      higher metabolic rates than mammals of the same size and yet live longer). It has
      rarely been experimentally tested within species. Here, we investigated the
      effects of increased energy expenditure, induced by cold exposure, on longevity
      in mice. Longevity was measured in groups of 60 male mice maintained at either 22
      degrees C (WW) or 10 degrees C (CC) throughout adult life. Forty additional mice
      were maintained at both of these temperatures to determine metabolic rate (by
      stable isotope turnover, gas exchange, and food intake) as well as the mass of
      body and organs of subsets of animals at four different ages. Because energy
      expenditure might affect longevity by either accumulating damage or by
      instantaneously affecting mortality rate, we included a third group of mice
      exposed to 10 degrees C early in life and to 22 degrees C afterward (CW).
      Exposure to cold increased mean daily energy expenditure by ca. 48% (from 47.8 kJ
      d(-1) in WW to 70.6 kJ d(-1) in CC mice, with CW intermediate at 59.9 kJ d(-1)).
      However, we observed no significant differences in median life span among the
      groups (WW, 832 d; CC, 834 d; CW, 751 d). CC mice had reduced body mass (lifetime
      mean 30.7 g) compared with WW mice (33.8 g), and hence their lifetime energy
      potential (LEP) per gram whole-body mass had an even larger excess than per
      individual. Greenberg ( 1999 ) has pointed out that the size of the energetically
      costly organs, rather than that of the whole body, may be relevant for the rate
      of-living idea. We therefore expressed LEP also in terms of energy expenditure
      per gram dry lean mass or per gram "metabolic" organ mass (i.e., heart, liver,
      kidneys, and brain). No matter how it was expressed, LEP in CC mice significantly
      exceeded that of WW mice. This result demonstrates that increased energy
      expenditure does not shorten life span and adds evidence to the intraspecific
      refutation of the rate-of-living theory. We suggest that increased energy
      expenditure has both positive and negative effects on different factors
      determining life span and that the relationship between energy turnover and
      longevity is fundamentally nonmonotonic.

PMID- 19115966
TI  - Two limonoids, khayalenoids A and B with an unprecedented 8-oxa
      tricyclo[4.3.2.0(2,7)]undecane motif, from Khaya senegalensis.
AB  - Two limonoids, namely khayalenoids A (1) and B (2) with an unprecedented 8-oxa
      tricyclo[4.3.2.0(2,7)]undecane motif in the nortriterpenoid core, were isolated
      from the stems of Khaya senegalensis. Their structures with absolute
      configuration were determined by spectroscopic data, X-ray crystallography, and
      CD analysis.

PMID- 19115967
TI  - Epidemiology and outcome of invasive fungal infection in adult hematopoietic stem
      cell transplant recipients: analysis of Multicenter Prospective Antifungal
      Therapy (PATH) Alliance registry.
AB  - BACKGROUND: With use of data from the Prospective Antifungal Therapy (PATH)
      Alliance registry, we performed this multicenter, prospective, observational
      study to assess the epidemiologic characters and outcomes of invasive fungal
      infection (IFI) in hematopoietic stem cell transplant (HSCT) recipients. METHODS:
      Sixteen medical centers from North America reported data on adult HSCT recipients
      with proven or probable IFI during the period July 2004 through September 2007.
      The distribution of IFIs and rates of survival at 6 and 12 weeks after diagnosis
      were studied. We used logistic regression models to determine risk factors
      associated with 6-week mortality for allogeneic HSCT recipients with invasive
      aspergillosis (IA). RESULTS: Two hundred thirty-four adult HSCT recipients with a
      total of 250 IFIs were included in this study. IA (59.2%) was the most frequent
      IFI, followed by invasive candidiasis (24.8%), zygomycosis (7.2%), and IFI due to
      other molds (6.8%). Voriconazole was the most frequently administered agent
      (68.4%); amphotericin B deoxycholate was administered to a few patients (2.1%).
      Ninety-three (46.7%) of 199 HSCT recipients with known outcome had died by week
      12. The 6-week survival rate was significantly greater for patients with IA than
      for those with invasive candidiasis and for those with IFI due to the Zygomycetes
      or other molds (P < .07). The 6-week mortality rate for HSCT recipients with IA
      was 21.5%. At 6 weeks, there was a trend toward a worse outcome among allogeneic
      HSCT recipients with IA who received myeloablative conditioning (P = .07);
      absence of mechanical ventilation or/and hemodialysis (P = .01) were associated
      with improved survival. CONCLUSIONS: IA remains the most commonly identified IFI
      among HSCT recipients, but rates of survival in persons with IA appear to have
      improved, compared with previously reported data. Invasive candidiasis and IFI
      due to molds other than Aspergillus species remain a significant problem in HSCT
      recipients.

PMID- 19115968
TI  - Isolated bladder dysfunction in human T lymphotropic virus type 1 infection.

PMID- 19115970
TI  - Burden of influenza-like illness and effectiveness of influenza vaccination among
      working adults aged 50-64 years.
AB  - BACKGROUND: Uncertainties regarding influenza disease impact and benefits of
      vaccination may contribute to low vaccination rates among adults aged 50-64
      years. METHODS: This prospective cohort study assessed the burden of influenza
      like illness (ILI) among working adults aged 50-64 years and the effectiveness of
      influenza vaccination in reducing the rate of ILI and productivity losses.
      Employees of the University of Minnesota (Minneapolis) were invited via e-mail to
      participate in the study during October 2006. The study data were collected using
      internet-based surveys at baseline (October 2006) and during the follow-up period
      (from November 2006 through April 2007). Months included in the 2006-2007
      influenza season were identified retrospectively from Minnesota Department of
      Health surveillance data. Vaccine effectiveness for reducing the rate of ILI, ILI
      associated health care use, the number of days of illness, work loss, and reduced
      on-the-job productivity during the influenza season were assessed using
      multivariable regression models after controlling for important confounders.
      RESULTS: Four hundred ninety-seven persons were included in the study, 85 (17.1%)
      of whom experienced an ILI. Among unvaccinated participants, ILI was responsible
      for 45% of all days of illness during the influenza season, 39% of all illness
      related work days lost, and 49% of all days with illness-related reduced on-the
      job productivity. In the multivariable regression analyses, vaccination was
      associated with a significant reduction in the rate of ILI (adjusted odds ratio,
      0.48; 95% confidence interval, 0.27-0.86) and fewer days of illness, absenteeism,
      and impaired on-the-job performance. CONCLUSION: ILIs were common among our study
      participants, accounting for a large portion of illness, work loss, and impaired
      work performance during the influenza season. Vaccination was associated with
      substantial health and productivity benefits. Vaccine delivery should be improved
      for this high-priority group.

PMID- 19115969
TI  - Early immunological predictors of neurodevelopmental outcomes in HIV-infected
      children.
AB  - BACKGROUND: A previous analysis of children infected with human immunodeficiency
      virus (HIV) in the Women and Infants Transmission Study showed a strong
      correlation between low activated CD8(+) T lymphocytes in the first 2 months of
      life and good immunological prognosis. We sought to extend these observations to
      neurodevelopmental prognosis. METHODS: Ninety-eight HIV-infected children born
      before 1994 with flow cytometric data from the first 2 months of life and
      adequate neurodevelopmental testing through age 30 months were studied. Children
      were divided into those with low (<or=5% CD8(+)HLA-DR(+) cells or <or=25%
      CD8(+)CD38(+) cells) or high (>5% CD8(+)HLA-DR(+) cells or >25% CD8(+)CD38(+)
      cells) immune activation at 1 and/or 2 months of age. Analysis was performed
      using survival analysis, Cox's proportional hazard regression, and longitudinal
      regression models. RESULTS: Absence of immune activation, measured as <or=5%
      CD8(+)HLA-DR(+) cells, was strongly associated with better performance on the
      psychomotor developmental index of the Bayley scales of infant development
      through the third year of life. This association persisted after adjustment for
      CD4 cell count, viral load, and progression to acquired immunodeficiency syndrome
      (P= .005). An association with the mental development index was also present (P=
      .048). Significant association between neurodevelopmental outcomes and <or=25%
      CD8(+)CD38(+) cells was not seen. CONCLUSIONS: In this prospective cohort study
      of HIV-infected children, there was a significant favorable association of low
      immune activation in peripheral T cells at age 1 or 2 months, measured by a low
      percentage of CD8(+)HLA-DR(+) cells, with subsequent psychomotor and mental
      development. This association was independent of other indices of severity and
      progression of HIV infection.

PMID- 19115971
TI  - Changing epidemiology of antimicrobial-resistant Streptococcus pneumoniae in the
      United States, 2004-2005.
AB  - BACKGROUND: The impact of pediatric 7-valent pneumococcal conjugate vaccination
      (PCV-7) on the population of Streptococcus pneumoniae in the United States was
      examined by determining the serotypes, antimicrobial resistance profiles, and
      genetic relatedness of isolates from patients with invasive and noninvasive
      infections during the 2004-2005 respiratory illness season. METHODS:
      Susceptibility testing, serotyping, and pulsed-field gel electrophoresis analysis
      were performed on 1647 S. pneumoniae isolates obtained from 41 US medical centers
      in 2004-2005 as part of a longitudinal antimicrobial resistance surveillance
      program. The results were compared with surveillance data from earlier periods.
      RESULTS: From the 1999-2000 to the 2004-2005 respiratory illness season, the
      prevalence of isolates with intermediate penicillin resistance (minimum
      inhibitory concentration, 0.1-1 microg/mL) increased from 12.7% to 17.9%,
      prevalence of penicillin-resistant isolates (minimum inhibitory concentration,
      >or=2 microg/mL) decreased from 21.5% to 14.6%, and prevalence of isolates
      resistant to erythromycin increased from 25.7% to 29.1% among S. pneumoniae
      isolates. The prevalence of multidrug resistance among isolates did not change
      (22.4% in 1999-2000 and 20.0% in 2004-2005). Sixty different serotypes were
      recognized among the isolates from 2004-2005; predominant serotypes were 19A
      (14.5%), 3 (11.2%), 6A (7.1%), 19F (7%), and 11A (6%). Serotypes that were
      included in PCV-7 accounted for 16.3% of isolates; 28.4% of strains isolated had
      PCV-7-related serotypes, and the remaining 55.3% of isolates had serotypes that
      were unrelated to PCV-7. The serotype distribution of the penicillin-resistant S.
      pneumoniae population changed from 1999-2000 to 2004-2005, with an increase in
      the prevalence of serotype 19A (1.5% to 35.4%) and serotype 35B (1.2% to 12.5%)
      and a decrease in the prevalence of most PCV-7 serotypes, including 23F (16.1% to
      5%), 9V (16.1% to 4.2%), 6B (13.7% to 3.8%), and 14 (18.5% to 2.9%). CONCLUSIONS:
      The penicillin-resistant S. pneumoniae population has changed; most isolates are
      now closely related to 2 Pneumococcal Molecular Epidemiology Network clones that
      increased in prevalence from 1999-2000 to 2004-2005 (Taiwan(19F)-14 [14.6% to
      36.7%; 60% were serotype 19A] and Utah(35B)-24 [0.9% to 16.3%]).

PMID- 19115972
TI  - Should HLA-B*5701 screening be performed in every ethnic group before starting
      abacavir?
AB  - Human leukocyte antigen allele (HLA)-B*5701 is associated with abacavir
      hypersensitivity. However, the carriage rate of HLA-B*5701 has rarely been
      studied in Asians. In 534 Korean patients with human immunodeficiency virus
      infection, HLA-B*5701 status was determined by polymerase chain reaction with HLA
      B*5701-specific primers. No patients had the HLA-B*5701 allele (95% confidence
      interval, 0%-0.7%). This explains the paucity of immunologically confirmed cases
      of abacavir hypersensitivity in Koreans.

PMID- 19115973
TI  - Early immune activation predicts central nervous system disease in HIV-infected
      infants: implications for early treatment.

PMID- 19115974
TI  - Efficacy of soap and water and alcohol-based hand-rub preparations against live
      H1N1 influenza virus on the hands of human volunteers.
AB  - BACKGROUND: Although pandemic and avian influenza are known to be transmitted via
      human hands, there are minimal data regarding the effectiveness of routine hand
      hygiene (HH) protocols against pandemic and avian influenza. METHODS: Twenty
      vaccinated, antibody-positive health care workers had their hands contaminated
      with 1 mL of 10(7) tissue culture infectious dose (TCID)(50)/0.1 mL live human
      influenza A virus (H1N1; A/New Caledonia/20/99) before undertaking 1 of 5 HH
      protocols (no HH [control], soap and water hand washing [SW], or use of 1 of 3
      alcohol-based hand rubs [61.5% ethanol gel, 70% ethanol plus 0.5% chlorhexidine
      solution, or 70% isopropanol plus 0.5% chlorhexidine solution]). H1N1
      concentrations were assessed before and after each intervention by viral culture
      and real-time reverse-transcriptase polymerase chain reaction (PCR). The natural
      viability of H1N1 on hands for >60 min without HH was also assessed. RESULTS:
      There was an immediate reduction in culture-detectable and PCR-detectable H1N1
      after brief cutaneous air drying--14 of 20 health care workers had H1N1 detected
      by means of culture (mean reduction, 10(3-4) TCID(50)/0.1 mL), whereas 6 of 20
      had no viable H1N1 recovered; all 20 health care workers had similar changes in
      PCR test results. Marked antiviral efficacy was noted for all 4 HH protocols, on
      the basis of culture results (14 of 14 had no culturable H1N1; (P< .002) and PCR
      results (P< .001; cycle threshold value range, 33.3-39.4), with SW statistically
      superior (P< .001) to all 3 alcohol-based hand rubs, although the actual
      difference was only 1-100 virus copies/microL. There was minimal reduction in
      H1N1 after 60 min without HH. CONCLUSIONS: HH with SW or alcohol-based hand rub
      is highly effective in reducing influenza A virus on human hands, although SW is
      the most effective intervention. Appropriate HH may be an important public health
      initiative to reduce pandemic and avian influenza transmission.

PMID- 19115975
TI  - Valuing influenza vaccine: medical, economic, and social benefits.

PMID- 19115976
TI  - Zoonotic vaccinia virus: clinical and immunological characteristics in a
      naturally infected patient.
AB  - Vaccinia virus was used as vaccine to eradicate smallpox. We report a zoonotic
      case of vaccinia virus infection in a 30-year-old patient who became infected
      after handling sick dairy cattle. The patient had inflamed lesions and systemic
      symptoms. Laboratory findings were indicative of down-modulated immune responses
      to the virus.

PMID- 19115977
TI  - Characterization of the nonionic microemulsions by EPR. I. Effect of solubilized
      drug on nanostructure.
AB  - The effect of the solubilized model drug, carbamazepine, on the internal
      structure of fully dilutable nonionic microemulsions was examined for the first
      time using electron paramagnetic resonance (EPR). Systems containing different
      surfactant to oil ratios, at two different pH values (4.6 and 8.5), with
      continuous dilution implementing structural transformations (micellar solution
      W/O-bicontinuous-O/W) were investigated. The internal order, micropolarity, and
      microviscosity were scrutinized utilizing pH-dependent amphiphilic probe 5
      doxylstearic acid (5-DSA). In the basic environment, the probe explored the
      vicinity of the surfactant head region; the deeper hydrophobic region of the
      surfactant tails was investigated in the acidic milieu. The study demonstrated
      that the EPR technique enables efficient monitoring of structural changes and
      examination of drug influence on structure in surfactant-poor systems. Lower
      order and microviscosity values were obtained in surfactant-poor systems in
      comparison to surfactant-rich systems. The drug functioned as a spacer of the
      surfactant molecules or as a cosurfactant depending on the formed microemulsion
      structure and the surfactant to oil ratio. The structural changes, pH variation,
      and presence of the drug did not alter the polarity parameter, indicating that
      the probe most likely does not sense a water environment in any of the examined
      systems. Under the basic conditions, higher microviscosity and order values were
      obtained in comparison to those at low pH, suggesting a higher order packing of
      the surfactant chains near the surfactant heads. The structural changes initiated
      in the vicinity of the surfactant heads, therefore, are more apparent in the
      basic environment. The ability to control and monitor the intramicellar
      interactions within drug carrier systems may be of significant interest for
      understanding the kinetics of drug release.

PMID- 19115978
TI  - Asymmetric construction of quaternary carbon centers by sequential conjugate
      addition of lithium amide and in situ alkylation: utility in the synthesis of (-)
      aspidospermidine.
AB  - Chiral diether ligand-controlled asymmetric conjugate addition of a lithium amide
      to cyclopentenecarboxylate and subsequent in situ alkylation gave a chiral
      cyclopentane derivative bearing a quaternary carbon with high enantio- and
      diastereoselectivity. The cyclopentane derivative was converted successfully to (
      )-aspidospermidine.

PMID- 19115979
TI  - Novel synthesis of a 1,3,5-trioxazatriquinane skeleton using a nitrogen clamp.
AB  - An alpha-hydroxyaldehyde derived from naltrexone was converted to an oxazoline
      dimer with ammonium chloride and sodium acetate in MeOH under reflux. The
      resulting dimer was treated with dl-camphorsulfonic acid in CHCl(3) to give the
      trimer. The method for trimer synthesis was also applied to general alpha
      hydroxyaldehydes to afford trimers in good yield.

PMID- 19115980
TI  - Enantioselective organocatalytic michael addition of malonates to alpha,beta
      unsaturated ketones.
AB  - A novel type of primary amine thiourea organocatalysts derived from 1,2
      diaminocyclohexane and 9-amino (9-deoxy) cinchona alkaloid was developed into
      asymmetric Michael addition of malonates to enones. A series of cyclic and
      acyclic enones could react very well with different malonates in the presence of
      4 with 0.5-10 mol % catalyst loading affording chiral Michael adducts with
      excellent yields and ee values.

PMID- 19115981
TI  - Complexation of lanthanides with nitrate at variable temperatures: thermodynamics
      and coordination modes.
AB  - Complexation of neodymium(III) with nitrate was studied at variable temperatures
      (25, 40, 55, and 70 degrees C) by spectrophotometry and microcalorimetry. The
      NdNO(3)(2+) complex is weak and becomes slightly stronger as the temperature is
      increased. The enthalpy of complexation at 25 degrees C was determined by
      microcalorimetry to be small and positive, 1.5 +/- 0.2 kJ x mol(-1), in good
      agreement with the trend of the stability constant at variable temperatures.
      Luminescence emission spectra and the lifetime of Eu(III) in nitrate solutions
      suggest that inner-sphere and bidentate complexes form between trivalent
      lanthanides (Nd(3+) and Eu(3+)) and nitrate in aqueous solutions. A specific ion
      interaction approach was used to obtain the stability constants of NdNO(3)(2+) at
      infinite dilution and variable temperatures.

PMID- 19115983
TI  - Immunoglobulin kappa chain locus on chromosome 2p12 and onchocerciasis.

PMID- 19115984
TI  - Nutrient supplementation and tuberculosis treatment outcome.

PMID- 19115987
TI  - Ethical consideration for use of carbapenems as treatment for sepsis due to
      carbapenem-resistant bacteria.

PMID- 19115991
TI  - Reliability of the interRAI suite of assessment instruments: a 12-country study
      of an integrated health information system.
AB  - BACKGROUND: A multi-domain suite of instruments has been developed by the
      interRAI research collaborative to support assessment and care planning in mental
      health, aged care and disability services. Each assessment instrument comprises
      items common to other instruments and specialized items exclusive to that
      instrument. This study examined the reliability of the items from five
      instruments supporting home care, long term care, mental health, palliative care
      and post-acute care. METHODS: Paired assessments on 783 individuals across 12
      nations were completed within 72 hours of each other by trained assessors who
      were blinded to the others' assessment. Reliability was tested using weighted
      kappa coefficients. RESULTS: The overall kappa mean value for 161 items which are
      common to 2 or more instruments was 0.75. The kappa mean value for specialized
      items varied among instruments from 0.63 to 0.73. Over 60% of items scored
      greater than 0.70. CONCLUSION: The vast majority of items exceeded standard cut
      offs for acceptable reliability, with only modest variation among instruments.
      The overall performance of these instruments showed that the interRAI suite has
      substantial reliability according to conventional cut-offs for interpreting the
      kappa statistic. The results indicate that interRAI items retain reliability when
      used across care settings, paving the way for cross domain application of the
      instruments as part of an integrated health information system.

PMID- 19115992
TI  - Interventions to prevent disability in frail community-dwelling elderly: a
      systematic review.
AB  - BACKGROUND: There is an interest for intervention studies aiming at the
      prevention of disability in community-dwelling physically frail older persons,
      though an overview on their content, methodological quality and effectiveness is
      lacking. METHODS: A search for clinical trials involved databases PubMed, CINAHL
      and Cochrane Central Register of Controlled Trials and manually hand searching.
      Trials that included community-dwelling frail older persons based on physical
      frailty indicators and used disability measures for outcome evaluation were
      included. The selection of papers and data-extraction was performed by two
      independent reviewers. Out of 4602 titles, 10 papers remained that met the
      inclusion criteria. Of these, 9 were of sufficient methodological quality and
      concerned 2 nutritional interventions and 8 physical exercise interventions.
      RESULTS: No evidence was found for the effect of nutritional interventions on
      disability measures. The physical exercise interventions involved 2 single
      component programs focusing on lower extremity strength and 6 multi-component
      programs addressing a variety of physical parameters. Out of 8 physical exercise
      interventions, three reported positive outcomes for disability. There was no
      evidence for the effect of single lower extremity strength training on
      disability. Differences between the multi-component interventions in e.g.
      individualization, duration, intensity and setting hamper the interpretation of
      the elements that consistently produced successful outcomes. CONCLUSION: There is
      an indication that relatively long-lasting and high-intensive multicomponent
      exercise programs have a positive effect on ADL and IADL disability for community
      living moderate physically frail older persons. Future research into disability
      prevention in physical frail older persons could be directed to more
      individualized and comprehensive programs.

PMID- 19115993
TI  - Association analyses of the interaction between the ADSS and ATM genes with
      schizophrenia in a Chinese population.
AB  - BACKGROUND: The blood-derived RNA levels of the adenylosuccinate synthase (ADSS)
      and ataxia telangiectasia mutated (ATM) genes were found to be down- and up
      regulated, respectively, in schizophrenics compared with controls, and ADSS and
      ATM were among eight biomarker genes to discriminate schizophrenics from normal
      controls. ADSS catalyzes the first committed step of AMP synthesis, while ATM
      kinase serves as a key signal transducer in the DNA double-strand breaks response
      pathway. It remains unclear whether these changes result from mutations or
      polymorphisms in the two genes. METHODS: Six SNPs in the ADSS gene and three SNPs
      in the ATM gene in a Chinese population of 488 schizophrenics and 516 controls
      were genotyped to examine their association with schizophrenia (SZ). Genotyping
      was performed using the Sequenom platform. RESULTS: There was no significant
      difference in the genotype, allele, or haplotype distributions of the nine SNPs
      between cases and controls. Using the Multifactor Dimensionality Reduction (MDR)
      method, we found that the interactions among rs3102460 in the ADSS gene and
      rs227061 and rs664143 in the ATM gene revealed a significant association with SZ.
      This model held a maximum testing accuracy of 60.4% and a maximum cross
      validation consistency of 10 out of 10. CONCLUSION: These findings suggest that
      the combined effects of the polymorphisms in the ADSS and ATM genes may confer
      susceptibility to the development of SZ in a Chinese population.

PMID- 19115994
TI  - Recurrent retroperitoneal hemorrhage in a patient with tuberous sclerosis
      complex: a case report.
AB  - BACKGROUND: Tuberous sclerosis complex (TSC) is an autosomal dominant disorder.
      It is characterized by seizures, mental retardation and hamartomatous lesions,
      including facial angiofibroma, subependymal giant cell astrocytoma, cardiac
      rhabdomyoma and renal angiomyolipoma (AML). AMLs can bleed severely in the
      retroperitoneal space. CASE PRESENTATION: Herein, we present the case of a TSC
      patient presenting with recurrent severe episodes of retroperitoneal hemorrhage
      from AMLs successfully managed by angio-embolization. CONCLUSION: Transarterial
      embolization is effective in preventing and controlling hemorrhage in patients
      with AMLs of the kidney.

PMID- 19115995
TI  - PTEN and rapamycin inhibiting the growth of K562 cells through regulating mTOR
      signaling pathway.
AB  - OBJECTIVE: To investigate, in vitro, the regulatory effects of tumor-suppressing
      gene PTEN on mTOR (mammalian target of rapamycin) signaling pathway, the effects
      of transfected PTEN and rapamycin on the growth inhibition, and apoptosis
      induction for human leukemia cell line K562 cells. METHODS: K562 cells were
      transfected with recombined adenovirus-PTEN vector containing green fluorescent
      protein (Ad-PTEN-GFP), followed by the treatment of the cells with or without
      rapamycin. The proliferation inhibition rate and apoptotic rate of these
      transfected and/or rapamycin treated K562 cells were measured by MTT assay and
      flow cytometry (FCM), the expression levels of PTEN-, mTOR-, cyclinD1- and
      P27kip1- mRNA were measured by real-time fluorescent relative-quantification
      reverse transcriptional PCR (FQ-PCR), the protein expression levels of PTEN, Akt,
      p-Akt were detected by western blotting. RESULTS: The proliferation of K562 cells
      was inhibited by PTEN gene transfection with/without the treatment of rapamycin.
      The expression levels of PTEN- and P27kip1- mRNA were up-regulated, and the mTOR-
      and cyclinD1- mRNA were down-regulated in K562 cells after the cells transfected
      with wild type PTEN gene and treated with rapamycin. CONCLUSION: PTEN and
      rapamycin inhibited mTOR expression by acting as an upstream regulator of mTOR.
      Low dose rapamycin in combination with over-expressed PTEN might have synergistic
      effects on inhibiting the proliferation and promoting apoptosis of K562 cells.

PMID- 19115996
TI  - The development of a mini-array for estimating the disease state of gastric
      adenocarcinoma by array CGH.
AB  - BACKGROUND: The treatment strategy usually depends on the disease state in the
      individual patient. However, it is difficult to estimate the disease state before
      treatment in many patients. The purpose of this study was to develop a BAC
      (bacterial artificial chromosome) mini-array allowing for the estimation of node
      metastasis, liver metastasis, peritoneal dissemination and the depth of tumor
      invasion in gastric cancers. METHODS: Initially, the DNA copy number aberrations
      (DCNAs) were analyzed by array-based comparative genomic hybridization (aCGH) in
      83 gastric adenocarcinomas as a training-sample set. Next, two independent
      analytical methods were applied to the aCGH data to identify the BAC clones with
      DNA copy number aberrations that were linked with the disease states. One of the
      methods, a decision-tree model classifier, identified 6, 4, 4, 4, and 7 clones
      for estimating lymph node metastasis, liver metastasis, peritoneal dissemination,
      depth of tumor invasion, and histological type, respectively. In the other
      method, a clone-by-clone comparison of the frequency of the DNA copy number
      aberrations selected 26 clones to estimate the disease states. RESULTS: By
      spotting these 50 clones together with 26 frequently or rarely involved clones
      and 62 reference clones, a mini-array was made to estimate the above parameters,
      and the diagnostic performance of the mini-array was evaluated for an independent
      set of 30 gastric cancers (blinded - sample set). In comparison to the
      clinicopathological features, the overall accuracy was 66.7% for node metastasis,
      86.7% for liver metastasis, 86.7% for peritoneal dissemination, and 96.7% for
      depth of tumor invasion. The intratumoral heterogeneity barely affected the
      diagnostic performance of the mini-array. CONCLUSION: These results suggest that
      the mini-array makes it possible to determine an optimal treatment for each of
      the patients with gastric adenocarcinoma.

PMID- 19115997
TI  - Correlation of three immunohistochemically detected markers of neuroendocrine
      differentiation with clinical predictors of disease progression in prostate
      cancer.
AB  - BACKGROUND: The importance of immuno-histological detection of neuroendocrine
      differentiation in prostatic adenocarcinoma with respect to disease at
      presentation and Gleason grade is gaining acceptance. There is limited literature
      on the relative significance of three commonly used markers of NE differentiation
      i.e. Chromogranin A (CgA), Neuron specific enolase (NSE) and Synaptophysin (Syn).
      In the current work we have assessed the correlation of immuno-histological
      detection of neuroendocrine differentiation in prostatic adenocarcinoma with
      respect to disease at presentation and Gleason grade and to determine the
      relative value of various markers. MATERIALS AND METHODS: Consecutive samples of
      malignant prostatic specimens (Transurethral resection of prostate or radical
      retropubic prostatectomy) from 84 patients between January 1991 and December 1998
      were evaluated by immunohistochemical staining (PAP technique) using selected
      neuroendocrine tumor markers i.e. Chromogranin A (CgA), Neuron specific enolase
      (NSE), and Synaptophysin (Syn). According to the stage at diagnosis, patients
      were divided into three groups. Group (i) included patients who had organ
      confined disease, group (ii) included patients with locally invasive disease, and
      group (iii) with distant metastasis. NE expression was correlated with Gleason
      sum and clinical stage at presentation and analyzed using Chi-Square test and one
      way ANNOVA. RESULTS: The mean age of the patients was 70 +/- 9.2 years. Group I
      had 14 patients, group II had 31 patients and group III had 39 patients. CgA was
      detected in 33 cases, Syn in 8 cases, and NSE in 44 cases. Expression of CgA was
      seen in 7% of group I, 37% in group II and 35% of group III patients (p 0.059).
      CgA (p 0.024) and NSE (p 0.006) had a significantly higher expression with
      worsening Gleason grade. CONCLUSION: CgA has a better correlation with disease at
      presentation than other markers used. Both NSE and CgA had increasing expression
      with worsening histological grade this correlation has a potential for use as a
      prognostic indicator. Limitations in the current work included small number and
      retrospective nature of work. The findings of this work needs validation in a
      larger cohort.

PMID- 19115998
TI  - What needs to change to increase chlamydia screening in general practice in
      Australia? The views of general practitioners.
AB  - BACKGROUND: Australia is considering implementing a chlamydia screening program
      in general practice. The views of general practitioners (GPs) are necessary to
      inform the design of the program. This paper aimed to investigate Australian GPs'
      views on how chlamydia screening could work in the Australian context. METHODS:
      This project used both qualitative interviews and a quantitative questionnaire.
      GPs were randomly selected from a national database of medical practitioners for
      both the qualitative and quantitative components. Semi-structured interviews were
      conducted with GPs and a thematic analysis conducted. The results of the
      interviews were used to design a quantitative postal questionnaire for completion
      by a larger sample of GPs. Up to three reminders were sent to non-responders.
      RESULTS: Twenty one GPs completed an interview and 255 completed the postal
      questionnaire. The results of the postal survey were in strong concordance with
      those of the interview. GPs identified a number of barriers to increased
      screening including lack of time, knowledge of GPs and the public about
      chlamydia, patient embarrassment and support for partner notification. GPs felt
      strongly that screening would be easier if there was a national program and if
      the public and GPs had a greater knowledge about chlamydia. Incentive payments
      and mechanisms for recall and reminders would facilitate screening. Greater
      support for contact tracing would be important if screening is to increase.
      CONCLUSION: Chlamydia screening in general practice is acceptable to Australian
      GPs. If screening is to succeed, policy makers must consider the facilitators
      identified by GPs.

PMID- 19115999
TI  - Cardiovascular autonomic function tests in an African population.
AB  - BACKGROUND: Diabetes mellitus is becoming increasingly common in sub-Saharan
      Africa. Autonomic dysfunction contributes to morbidity and mortality in diabetic
      patients. Data on autonomic dysfunction in the African population is scarce, and
      no reference values for standardized autonomic function tests are available. The
      aim of this study was to establish cut off values for five easy-to-use
      cardiovascular autonomic function tests that may be suitable for resource-poor
      settings. METHODS: We recruited 276 healthy African individuals, 156 men and 120
      women, aged > 20 years. Participants were tested for (1) resting heart rate (HR),
      (2) HR variation in response to deep breathing, (3) HR response to standing, and
      (4) postural changes in systolic and diastolic blood pressure (SBP and DBP).
      Respective cut-off values were calculated according to the 95th or 5th
      percentile. RESULTS: Taking an association of the autonomic test results with
      gender and age into consideration, we defined the following cut-off values:
      resting HR (bpm) >or= 89 for men and >or= 97 for women; HR (bpm) in response to
      deep breathing <or= 13, <or= 11, <or= 9, <or= 8, and <or= 7 for age groups 20-29,
      30-39, 40-49, 50-59, and 60+ years, respectively; HR (bpm) in response to
      standing <or= 14 for 20-29 years, and <or= 11 for 30+ years; postural decreases
      in SBP >or= 17 mmHg for all age groups; and postural decreases in DBP (mmHg) >or=
      2 for men and >or= 5 for women. CONCLUSION: The test battery revealed cut-off
      values different from those measured in Caucasians. Further studies are
      recommended a) to assess whether these cut off values are generally applicable,
      and b) to establish population specific reference values for Africans.

PMID- 19116000
TI  - Sickness absence and self-reported health a population-based study of 43,600
      individuals in central Sweden.
AB  - BACKGROUND: Sickness absence is very high in Sweden. The reasons for this
      phenomenon are not well known. The aim of this study was to investigate the
      association between degree of self-reported sickness absence and health. The
      hypothesis was that individuals with long-term sickness absence would report more
      symptoms and lower self-rated health. Another hypothesis was that women are more
      likely to self-rate psychiatric diagnoses compared to men, who are more likely to
      self-rate musculoskeletal diagnoses. METHODS: The data was obtained with a postal
      survey questionnaire answered by 43,589 individuals, a Swedish random population
      sample of men and women aged 18-84 years. The response rate was 65%. This study
      included 19,826 individuals aged 18-64 years old and still at work. They were
      divided into four groups, based on the number of reported days of sickness
      absence during the past year. RESULTS: Approximately 40% of the individuals at
      work mentioned that they had been absent due to illness sometime during the past
      year. Of those who had been absent 90 days or more, two thirds were women. There
      was a significant difference between the groups in self-rated health (p < 0.05).
      Every fifth woman (19.4%) and every fourth man (25.9%) in the group with a
      sickness absence of more than 89 days rated their health as poor or very poor,
      but a large proportion, 43.5% of the women and 31.6% of the men, rated their
      health as good. Long-term illnesses and complaints differed between the groups.
      The correlations between the groups and illness were mostly significant (p <
      0.01). Two thirds of the subjects had both psychiatric and musculoskeletal
      symptoms. There was a significant difference among them, as men more often had
      musculoskeletal diagnoses. One third had only psychiatric or musculoskeletal
      symptoms and in those groups there were no significant diagnosis differences
      between the sexes. CONCLUSION: Individuals with long-term sickness absence
      reported more symptoms and lower self-rated health than did those who had not
      been absent at all, and than those who had been ill 1-28 days. Men and women sick
      listed 29 days or more generally reported more illness and complaints. No sex
      differences among psychiatric and musculoskeletal diagnoses were found, but when
      reported both psychiatric and musculoskeletal symptoms the musculoskeletal
      diagnoses were significant among men.

PMID- 19116001
TI  - Atypical onset of diabetes in a teenage girl: a case report.
AB  - BACKGROUND: Chorea, hemichorea-hemiballismus and severe partial seizures may be
      the presenting feature of nonketotic hyperglycemia in older adults with type 2
      diabetes, but cases in children with type 1 diabetes are rare, since the most
      easily recognized symptoms of type 1 diabetes in children are secondary to
      hyperglycemia, glycosuria, and ketoacidosis. CASE PRESENTATION: A previously
      healthy 15-year-old girl presents with sudden onset of right-sided chorea. Brain
      CT did not detect any abnormal density areas. A T1-weighted image of brain MRI
      was normal. Investigations revealed hyperglycemia with absent ketones and normal
      serum osmolality. Achievement of normoglycemia with insulin therapy determined
      the involuntary movements to regress completely within a day. The direct effect
      of hyperglycemia could be the pathogenesis of the chorea in our patient. Severe
      hyperglycemia without ketosis at the clinical onset of insulin-dependent diabetes
      mellitus (type 1) has been reported in children and adolescents, but nonketotic
      hyperglycemia is an unusual cause of chorea-ballismus in children, and chorea
      ballismus is also a rare manifestation of primary diabetes mellitus. CONCLUSION:
      The importance of clinical evaluation, laboratory testing and neuroimaging for
      the differential diagnostics of chorea is emphasized.

PMID- 19116002
TI  - Universal ligation-detection-reaction microarray applied for compost microbes.
AB  - BACKGROUND: Composting is one of the methods utilised in recycling organic
      communal waste. The composting process is dependent on aerobic microbial activity
      and proceeds through a succession of different phases each dominated by certain
      microorganisms. In this study, a ligation-detection-reaction (LDR) based
      microarray method was adapted for species-level detection of compost microbes
      characteristic of each stage of the composting process. LDR utilises the
      specificity of the ligase enzyme to covalently join two adjacently hybridised
      probes. A zip-oligo is attached to the 3'-end of one probe and fluorescent label
      to the 5'-end of the other probe. Upon ligation, the probes are combined in the
      same molecule and can be detected in a specific location on a universal
      microarray with complementary zip-oligos enabling equivalent hybridisation
      conditions for all probes. The method was applied to samples from Nordic
      composting facilities after testing and optimisation with fungal pure cultures
      and environmental clones. RESULTS: Probes targeted for fungi were able to detect
      0.1 fmol of target ribosomal PCR product in an artificial reaction mixture
      containing 100 ng competing fungal ribosomal internal transcribed spacer (ITS)
      area or herring sperm DNA. The detection level was therefore approximately 0.04%
      of total DNA. Clone libraries were constructed from eight compost samples. The
      LDR microarray results were in concordance with the clone library sequencing
      results. In addition a control probe was used to monitor the per-spot
      hybridisation efficiency on the array. CONCLUSION: This study demonstrates that
      the LDR microarray method is capable of sensitive and accurate species-level
      detection from a complex microbial community. The method can detect key species
      from compost samples, making it a basis for a tool for compost process monitoring
      in industrial facilities.

PMID- 19116003
TI  - Maternal death after oocyte donation at high maternal age: case report.
AB  - BACKGROUND: The percentage of women giving birth after the age of 35 increased in
      many western countries. The number of women remaining childless also increased,
      mostly due to aging oocytes. The method of oocyte donation offers the possibility
      for infertile older women to become pregnant. Gestation after oocyte-donation
      IVF, however, is not without risks for the mother, especially at advanced age.
      CASE PRESENTATION: An infertile woman went abroad for oocyte-donation-IVF, since
      this treatment is not offered in The Netherlands after the age of 45. The first
      oocyte donation treatment resulted in multiple gestation, but was ended by
      induced abortion: the woman could not cope with the idea of being pregnant with
      twins. During the second pregnancy after oocyte donation, at the age of 50, she
      was mentally more stable. The pregnancy, again a multiple gestation, was
      uneventful until delivery. Immediately after delivery the woman had hypertension
      with nausea and vomiting. A few hours later she had an eclamptic fit. HELLP
      syndrome was diagnosed. She died due to cerebral haemorrhage. CONCLUSION: In The
      Netherlands, the age limit for women receiving donor oocytes is 45 years and
      commercial oocyte donation is forbidden by law. In other countries there is no
      age limit, the reason why some women are going abroad to receive the treatment of
      their choice. Advanced age, IVF and twin pregnancy are all risk factors for pre
      eclampsia, the leading cause of maternal death in The Netherlands.Patient
      autonomy is an important ethical principle, but doctors are also bound to the
      principle of 'not doing harm', and do have the right to refuse medical treatment
      such as IVF-treatment. The discussion whether women above 50 should have children
      is still not closed. If the decision is made to offer this treatment to a woman
      at advanced age, the doctor should counsel her intensively about the risks before
      treatment is started.

PMID- 19116004
TI  - Reuse of single-dose nevirapine in subsequent pregnancies for the prevention of
      mother-to-child HIV transmission in Lusaka, Zambia: a cohort study.
AB  - BACKGROUND: Single-dose nevirapine (SDNVP) for the prevention of mother-to-child
      HIV transmission (PMTCT) results in the selection of resistance mutants among HIV
      infected mothers. The effects of these mutations on the efficacy of SDNVP use in
      a subsequent pregnancy are not well understood. METHODS: We compared risks of
      perinatal HIV transmission between multiparous women who had previously received
      a dose of SDNVP (exposed) and those that had not (unexposed) and who were given
      SDNVP for the index pregnancy within a PMTCT clinical study. We also compared
      transmission risks among exposed and unexposed women who had two consecutive
      pregnancies within the trial. Logistic regression modeling was used to adjust for
      possible confounders. RESULTS: Transmission risks did not differ between 59 SDNVP
      exposed and 782 unexposed women in unadjusted analysis or after adjustment for
      viral load and disease stage (adjusted odds ratio 0.6, 95% confidence interval
      [CI] 0.2 to 2.0). Among 43 women who had two consecutive pregnancies during the
      study, transmission risks were 7% (95% CI 1% to 19%) at both the first
      (unexposed) and second (exposed) delivery. The results were unchanged, if infant
      death was included as an outcome. CONCLUSION: These data suggest that the
      efficacy of SDNVP may not be diminished when reused in subsequent pregnancies.

PMID- 19116005
TI  - Clustering of serotypes in a longitudinal study of Streptococcus pneumoniae
      carriage in three day care centres.
AB  - BACKGROUND: Streptococcus pneumoniae (pneumococcus) causes a wide range of
      clinical manifestations that together constitute a major burden of disease
      worldwide. The main route of pneumococcal transmission is through asymptomatic
      colonisation of the nasopharynx. Studies of transmission are currently of general
      interest because of the impact of the new conjugate-polysaccharide vaccines on
      nasopharyngeal colonisation (carriage). Here we report the first longitudinal
      study of pneumococcal carriage that records serotype specific exposure to
      pneumococci simultaneously within the two most important mixing groups, families
      and day care facilities. METHODS: We followed attendees (N = 59) with their
      family members (N = 117) and the employees (N = 37) in three Finnish day care
      centres for 9 months with monthly sampling of nasopharyngeal carriage.
      Pneumococci were cultured, identified and serotyped by standard methods. RESULTS:
      Children in day care constitute a core group of pneumococcal carriage: of the 36
      acquisitions of carriage with documented exposure to homologous pneumococci, the
      attendee had been exposed in her/his day care centre in 35 cases and in the
      family in 9 cases. Day care children introduce pneumococci to the family: 66% of
      acquisitions of a new serotype in a family were associated with simultaneous or
      previous carriage of the same type in the child attending day care. Consequently,
      pneumococcal transmission was found to take place as micro-epidemics driven by
      the day care centres. Each of the three day care centres was dominated by a
      serotype of its own, accounting for 100% of the isolates of that serotype among
      all samples from the day care attendees. CONCLUSION: The transmission of
      pneumococci is more intense within than across clusters defined by day care
      facilities. The ensuing micro-epidemic behaviour enhances pneumococcal
      transmission.

PMID- 19116006
TI  - Gene expression meta-analysis identifies metastatic pathways and transcription
      factors in breast cancer.
AB  - BACKGROUND: Metastasis is believed to progress in several steps including
      different pathways but the determination and understanding of these mechanisms is
      still fragmentary. Microarray analysis of gene expression patterns in breast
      tumors has been used to predict outcome in recent studies. Besides classification
      of outcome, these global expression patterns may reflect biological mechanisms
      involved in metastasis of breast cancer. Our purpose has been to investigate
      pathways and transcription factors involved in metastasis by use of gene
      expression data sets. METHODS: We have analyzed 8 publicly available gene
      expression data sets. A global approach, "gene set enrichment analysis" as well
      as an approach focusing on a subset of significantly differently regulated genes,
      GenMAPP, has been applied to rank pathway gene sets according to differential
      regulation in metastasizing tumors compared to non-metastasizing tumors. Meta
      analysis has been used to determine overrepresentation of pathways and
      transcription factors targets, concordant deregulated in metastasizing breast
      tumors, in several data sets. RESULTS: The major findings are up-regulation of
      cell cycle pathways and a metabolic shift towards glucose metabolism reflected in
      several pathways in metastasizing tumors. Growth factor pathways seem to play
      dual roles; EGF and PDGF pathways are decreased, while VEGF and sex-hormone
      pathways are increased in tumors that metastasize. Furthermore, migration,
      proteasome, immune system, angiogenesis, DNA repair and several signal
      transduction pathways are associated to metastasis. Finally several transcription
      factors e.g. E2F, NFY, and YY1 are identified as being involved in metastasis.
      CONCLUSION: By pathway meta-analysis many biological mechanisms beyond major
      characteristics such as proliferation are identified. Transcription factor
      analysis identifies a number of key factors that support central pathways.
      Several previously proposed treatment targets are identified and several new
      pathways that may constitute new targets are identified.

PMID- 19116007
TI  - Subacute and chronic, non-specific back and neck pain: cognitive-behavioural
      rehabilitation versus primary care. A randomized controlled trial.
AB  - BACKGROUND: In the industrial world, non-specific back and neck pain (BNP) is the
      largest diagnostic group underlying sick-listing. For patients with subacute and
      chronic (= full-time sick-listed for 43 - 84 and 85 - 730 days, respectively)
      BNP, cognitive-behavioural rehabilitation was compared with primary care. The
      specific aim was to answer the question: within an 18-month follow-up, will the
      outcomes differ in respect of sick-listing and number of health-care visits?
      METHODS: After stratification by age (< or = 44/> or = 45 years) and
      subacute/chronic BNP, 125 Swedish primary-care patients were randomly allocated
      to cognitive-behavioural rehabilitation (rehabilitation group) or continued
      primary care (primary-care group). Outcome measures were Return-to-work share
      (percentage) and Return-to-work chance (hazard ratios) over 18 months, Net days
      (crude sick-listing days x degree), and the number of Visits (to physicians,
      physiotherapists etc.) over 18 months and the three component six-month periods.
      Descriptive statistics, Cox regression and mixed-linear models were used.
      RESULTS: All patients: Return-to-work share and Return-to-work chance were
      equivalent between the groups. Net days and Visits were equivalent over 18 months
      but decreased significantly more rapidly for the rehabilitation group over the
      six-month periods (p < .05). Subacute patients: Return-to-work share was
      equivalent. Return-to-work chance was significantly greater for the
      rehabilitation group (hazard ratio 3.5 [95%CI1.001 - 12.2]). Net days were
      equivalent over 18 months but decreased significantly more rapidly for the
      rehabilitation group over the six-month periods and there were 31 days fewer in
      the third period. Visits showed similar though non-significant differences and
      there were half as many in the third period. Chronic patients: Return-to-work
      share, Return-to-work chance and Net days were equivalent. Visits were equivalent
      over 18 months but tended to decrease more rapidly for the rehabilitation group
      and there were half as many in the third period (non-significant). CONCLUSION:
      The results were equivalent over 18 months. However, there were indications that
      cognitive-behavioural rehabilitation in the longer run might be superior to
      primary care. For subacute BNP, it might be superior in terms of sick-listing and
      health-care visits; for chronic BNP, in terms of health-care visits only. More
      conclusive results concerning this possible long-term effect might require a
      longer follow-up.

PMID- 19116008
TI  - A case of radiation-induced sternal malignant fibrous histiocytoma treated with
      neoadjuvant chemotherapy and surgical resection.
AB  - BACKGROUND: Primary sternal malignant fibrous histiyocytoma (MFH) is highly rare.
      Effective treatment modality is surgical resection with wide margins. However, to
      date, the effects of radiotherapy or chemotherapy has not been clearly defined.
      CASE PRESENTATION: Herein, we aimed to present a 50-year old female patient with
      MFH occurred in the radiotherapy field who had had surgical procedure for breast
      cancer 19 years ago and had followed by radiotherapy. Neoadjuvant chemotherapy
      was applied for MFH due to cardiac and mediastinal vascular invasion. Wide
      resection was carried out for the mass after having been decreased in size
      following neoadjuvant chemotherapy. CONCLUSION: Neoadjuvant chemotherapy was an
      effective method. In planning the surgical resection, the size of the tumor
      before chemotherapy should be considered as the initial size and surgical margins
      should be determined accordingly.

PMID- 19116009
TI  - IFN-gamma, IL-4 and IL-13 modulate responsiveness of human airway smooth muscle
      cells to IL-13.
AB  - BACKGROUND: IL-13 is a critical mediator of allergic asthma and associated airway
      hyperresponsiveness. IL-13 acts through a receptor complex comprised of IL
      13Ralpha1 and IL-4Ralpha subunits with subsequent activation of signal transducer
      and activator of transcription 6 (STAT6). The IL-13Ralpha2 receptor may act as a
      decoy receptor. In human airway smooth muscle (HASM) cells, IL-13 enhances
      cellular proliferation, calcium responses to agonists and induces eotaxin
      production. We investigated the effects of pre-treatment with IL-4, IL-13 and IFN
      gamma on the responses of HASM cells to IL-13. METHODS: Cultured HASM were
      examined for expression of IL-13 receptor subunits using polymerase chain
      reaction, immunofluorescence microscopy and flow cytometry. Effects of cytokine
      pre-treatment on IL-13-induced cell responses were assessed by looking at STAT6
      phosphorylation using Western blot, eotaxin secretion and calcium responses to
      histamine. RESULTS: IL-13Ralpha1, IL-4Ralpha and IL-13Ralpha2 subunits were
      expressed on HASM cells. IL-13 induced phosphorylation of STAT6 which reached a
      maximum by 30 minutes. Pre-treatment with IL-4, IL-13 and, to a lesser degree,
      IFN-gamma reduced peak STAT6 phosphorylation in response to IL-13. IL-13, but not
      IFN-gamma, pre-treatment abrogated IL-13-induced eotaxin secretion. Pre-treatment
      with IL-4 or IL-13 abrogated IL-13-induced augmentation of the calcium transient
      evoked by histamine. Cytokine pre-treatment did not affect expression of IL
      13Ralpha1 and IL-4Ralpha but increased expression of IL-13Ralpha2. An anti-IL
      13Ralpha2 neutralizing antibody did not prevent the cytokine pre-treatment
      effects on STAT6 phosphorylation. Cytokine pre-treatment increased SOCS-1, but
      not SOCS-3, mRNA expression which was not associated with significant increases
      in protein expression. CONCLUSION: Pre-treatment with IL-4 and IL-13, but not IFN
      gamma, induced desensitization of the HASM cells to IL-13 as measured by eotaxin
      secretion and calcium transients to histamine. The mechanism of IL-4 and IL-13
      induced desensitization does not appear to involve either downregulation of
      receptor expression or induction of the IL-13Ralpha2 or the SOCS proteins.

PMID- 19116010
TI  - Comparative genomics of mutualistic viruses of Glyptapanteles parasitic wasps.
AB  - BACKGROUND: Polydnaviruses, double-stranded DNA viruses with segmented genomes,
      have evolved as obligate endosymbionts of parasitoid wasps. Virus particles are
      replication deficient and produced by female wasps from proviral sequences
      integrated into the wasp genome. These particles are co-injected with eggs into
      caterpillar hosts, where viral gene expression facilitates parasitoid survival
      and, thereby, survival of proviral DNA. Here we characterize and compare the
      encapsidated viral genome sequences of bracoviruses in the family Polydnaviridae
      associated with Glyptapanteles gypsy moth parasitoids, along with near complete
      proviral sequences from which both viral genomes are derived. RESULTS: The
      encapsidated Glyptapanteles indiensis and Glyptapanteles flavicoxis bracoviral
      genomes, each composed of 29 different size segments, total approximately 517 and
      594 kbp, respectively. They are generated from a minimum of seven distinct loci
      in the wasp genome. Annotation of these sequences revealed numerous novel
      features for polydnaviruses, including insect-like sugar transporter genes and
      transposable elements. Evolutionary analyses suggest that positive selection is
      widespread among bracoviral genes. CONCLUSIONS: The structure and organization of
      G. indiensis and G. flavicoxis bracovirus proviral segments as multiple loci
      containing one to many viral segments, flanked and separated by wasp gene
      encoding DNA, is confirmed. Rapid evolution of bracovirus genes supports the
      hypothesis of bracovirus genes in an 'arms race' between bracovirus and
      caterpillar. Phylogenetic analyses of the bracoviral genes encoding sugar
      transporters provides the first robust evidence of a wasp origin for some
      polydnavirus genes. We hypothesize transposable elements, such as those described
      here, could facilitate transfer of genes between proviral segments and host DNA.

PMID- 19116011
TI  - Adolescent and adult first time mothers' health seeking practices during
      pregnancy and early motherhood in Wakiso district, central Uganda.
AB  - BACKGROUND: Maternal health services have a potentially critical role in the
      improvement of reproductive health. In order to get a better understanding of
      adolescent mothers'needs we compared health seeking practices of first time
      adolescent and adult mothers during pregnancy and early motherhood in Wakiso
      district, Uganda. METHODS: This was a cross-sectional study conducted between May
      and August, 2007 in Wakiso district. A total of 762 women (442 adolescents and
      320 adult) were interviewed using a structured questionnaire. We calculated odds
      ratios with their 95% CI for antenatal and postnatal health care seeking,
      stigmatisation and violence experienced from parents comparing adolescents to
      adult first time mothers. STATA V.8 was used for data analysis. RESULTS:
      Adolescent mothers were significantly more disadvantaged in terms of health care
      seeking for reproductive health services and faced more challenges during
      pregnancy and early motherhood compared to adult mothers. Adolescent mothers were
      more likely to have dropped out of school due to pregnancy (OR = 3.61, 95% CI:
      2.40-5.44), less likely to earn a salary (OR = 0.43, 95%CI: 0.24-0.76), and more
      likely to attend antenatal care visits less than four times compared to adult
      mothers (OR = 1.52, 95%CI: 1.12-2.07). Adolescents were also more likely to
      experience violence from parents (OR = 2.07, 95%CI: 1.39-3.08) and to be
      stigmatized by the community (CI = 1.58, 95%CI: 1.09-2.59). In early motherhood,
      adolescent mothers were less likely to seek for second and third vaccine doses
      for their infants [Polio2 (OR = 0.73, 95% CI: 0.55-0.98), Polio3 (OR = 0.70: 95%
      CI: 0.51-0.95), DPT2 (OR = 0.71, 95% CI: 0.53-0.96), DPT3 (OR = 0.68, 95% CI:
      0.50-0.92)] compared to adult mothers. These results are compelling and call for
      urgent adolescent focused interventions. CONCLUSION: Adolescents showed poorer
      health care seeking behaviour for themselves and their children, and experienced
      increased community stigmatization and violence, suggesting bigger challenges to
      the adolescent mothers in terms of social support. Adolescent friendly
      interventions such as pregnancy groups targeting to empower pregnant adolescents
      providing information on pregnancy, delivery and early childhood care need to be
      introduced and implemented.

PMID- 19116012
TI  - The management of cancer in the elderly: targeted therapies in oncology.
AB  - Cancer is universally considered a disease of ageing. Today the management of
      elderly cancer patients poses many specific problems and it should be revisited
      in the light of the most recent advances in both diagnosis and treatment of human
      malignancies. In particular, the potential use of novel therapeutic options,
      based on therapeutic agents raised against molecular targets (the so called
      targeted therapy), appears to be promising in this clinical settings especially
      in view of the limited side-effects. The mainstays of cancer treatment during the
      twentieth century were surgery, radiation and chemotherapy. However, surgery is
      not curative in metastatic disease, radiation and chemotherapy are limited by
      side effects because they can't discriminate between healthy and cancerous cells.
      When key molecular changes responsible for malignant transformation were
      identified (e.g. growth factors and their receptors), it was hoped that new
      targeted agents, by inhibiting cancer-specific pathways, would spare normal cells
      and thereby offer improved safety benefits and a higher therapeutic index over
      standard chemotherapeutics. The most common targeted therapies used in clinical
      practice, i.e. monoclonal antibodies and small molecules, are described.

PMID- 19116013
TI  - Primary lymphoma of the head and neck: two case reports and review of the
      literature.
AB  - BACKGROUND: The head and neck is the second most common region for the extra
      nodal lymphomas after that of gastrointestinal tract. Approximately 2.5% of
      malignant lymphoma arises in the oral and para-oral region. In this paper we
      report two cases of early stage head and neck lymphoma which were managed
      successfully with chemotherapy and a review of the related literature. CASES
      PRESENTATION: The first case concerns a 48 years male patient having a diffuse
      large B-Cell lymphoma of the oropharynx at early bulky stage. This patient was
      managed successfully with 7 of Rituximab 375 mg/m2, Cyclophosphamide 750 mg/m2
      d1, Doxorubicine 50 mg/m2 d1, Vincristine 1.4 mg/m2 d1, and prednisone 50 mg/m2
      d1-5 (RCHOP) regimen. The second case concerns a 50 years female patient having
      the nasal natural killer (NK)/T-cell lymphoma of the left nasal pit at early
      stage. This case was managed successfully with 6 of Cyclophosphamide 750 mg/m2
      d1, Doxorubicine 50 mg/m2 d1, Vincristine 1.4 mg/m2 d1, and prednisone 50 mg/m2
      d1-5 (CHOP) regimen. CONCLUSION: These two cases highlight the important role of
      CHOP based chemotherapy for achieving successful treatment cure for patients
      having an early stage head and neck lymphoma.

PMID- 19116014
TI  - Baseline left bundle branch block with right bundle branch escape complexes in a
      patient with coronary artery disease, presents like an alternating bundle branch
      block: a case report.
AB  - Alternating bundle branch block (ABBB) is a less commonly encountered phenomenon
      with the advent of re-perfusion therapy for acute myocardial infarction. ECGs
      simulating the appearance of an ABBB need to be carefully analysed. We present an
      ECG showing a baseline Left Bundle Branch Block(LBBB) progressing to a high grade
      AV block with escape complexes having a Right Bundle Branch Block (RBBB)
      morphology. Such an ECG can be mistaken for an ABBB if not analysed carefully.

PMID- 19116015
TI  - Molecular cloning and characterization of a novel pyrethroid-hydrolyzing esterase
      originating from the Metagenome.
AB  - BACKGROUND: Pyrethroids and pyrethrins are widely used insecticides. Extensive
      applications not only result in pest resistance to these insecticides, but also
      may lead to environmental issues and human exposure. Numerous studies have shown
      that very high exposure to pyrethroids might cause potential problems to man and
      aquatic organisms. Therefore, it is important to develop a rapid and efficient
      disposal process to eliminate or minimize contamination of surface water,
      groundwater and agricultural products by pyrethroid insecticides. Bioremediation
      is considered to be a reliable and cost-effective technique for pesticides
      abatement and a major factor determining the fate of pyrethroid pesticides in the
      environment, and suitable esterase is expected to be useful for potential
      application for detoxification of pyrethroid residues. Soil is a complex
      environment considered as one of the main reservoirs of microbial diversity on
      the planet. However, most of the microorganisms in nature are inaccessible as
      they are uncultivable in the laboratory. Metagenomic approaches provide a
      powerful tool for accessing novel valuable genetic resources (novel enzymes) and
      developing various biotechnological applications. RESULTS: The pyrethroid
      pesticides residues on foods and the environmental contamination are a public
      safety concern. Pretreatment with pyrethroid-hydrolyzing esterase has the
      potential to alleviate the conditions. To this end, a pyrethroid-hydrolyzing
      esterase gene was successfully cloned using metagenomic DNA combined with
      activity-based functional screening from soil, sequence analysis of the DNA
      responsible for the pye3 gene revealed an open reading frame of 819 bp encoding
      for a protein of 272 amino acid residues. Extensive multiple sequence alignments
      of the deduced amino acid of Pye3 with the most homologous carboxylesterases
      revealed moderate identity (45-49%). The recombinant Pye3 was heterologously
      expressed in E. coli BL21(DE3), purified and characterized. The molecular mass of
      the native enzyme was approximately 31 kDa as determined by gel filtration. The
      results of sodium dodecyl sulfate-polyacrylamide gel electrophoresis and the
      deduced amino acid sequence of the Pye3 indicated molecular mass of 31 kDa and
      31.5 kDa, respectively, suggesting that the Pye3 is a monomer. The purified Pye3
      not only degraded all pyrethroid pesticides tested, but also hydrolyzed rho
      nitrophenyl esters of medium-short chain fatty acids, indicating that the Pye3 is
      an esterase with broader specificity. The Km values for trans-Permethrin and cis
      permethrin are 0.10 muM and 0.18 muM, respectively, and these catalytic
      properties were superior to carboxylesterases from resistant insects and mammals.
      The catalytic activity of the Pye3 was strongly inhibited by Hg2+, Ag+, rho
      chloromercuribenzoate, whereas less pronounced effect was observed in the
      presence of divalent cations, the chelating agent EDTA and phenanthroline.
      CONCLUSION: A novel pyrethroid-hydrolyzing esterase gene was successfully cloned
      using metagenomic DNA combined with activity-based functional screening from
      soil, the broader substrate specificities and higher activity of the pyrethroid
      hydrolyzing esterase (Pye3) make it an ideal candidate for in situ for
      detoxification of pyrethroids where they cause environmental contamination
      problems. Consequently, metagenomic DNA clone library offers possibilities to
      discover novel bio-molecules through the expression of genes from uncultivated
      bacteria.

PMID- 19116016
TI  - Revised estimates of influenza-associated excess mortality, United States, 1995
      through 2005.
AB  - BACKGROUND: Excess mortality due to seasonal influenza is thought to be
      substantial. However, influenza may often not be recognized as cause of death.
      Imputation methods are therefore required to assess the public health impact of
      influenza. The purpose of this study was to obtain estimates of monthly excess
      mortality due to influenza that are based on an epidemiologically meaningful
      model. METHODS AND RESULTS: U.S. monthly all-cause mortality, 1995 through 2005,
      was hierarchically modeled as Poisson variable with a mean that linearly depends
      both on seasonal covariates and on influenza-certified mortality. It also allowed
      for overdispersion to account for extra variation that is not captured by the
      Poisson error. The coefficient associated with influenza-certified mortality was
      interpreted as ratio of total influenza mortality to influenza-certified
      mortality. Separate models were fitted for four age categories (< 18, 18-49, 50
      64, 65+). Bayesian parameter estimation was performed using Markov Chain Monte
      Carlo methods. For the eleven year study period, a total of 260,814 (95% CI:
      201,011-290,556) deaths was attributed to influenza, corresponding to an annual
      average of 23,710, or 0.91% of all deaths. CONCLUSION: Annual estimates for
      influenza mortality were highly variable from year to year, but they were
      systematically lower than previously published estimates. The excellent fit of
      our model with the data suggest validity of our estimates.

PMID- 19116018
TI  - mRNA expression of the DNA replication-initiation proteins in epithelial
      dysplasia and squamous cell carcinoma of the tongue.
AB  - BACKGROUND: The tongue squamous cell carcinomas (SCCs) are characterized by high
      mitotic activity, and early detection is desirable. Overexpression of the DNA
      replication-initiation proteins has been associated with dysplasia and
      malignancy. Our aim was to determine whether these proteins are useful biomarkers
      for assessing the development of tongue SCC. METHODS: We analyzed the mRNA
      expression of CDC6, CDT1, MCM2 and CDC45 in formalin-fixed, paraffin-embedded
      benign and malignant tongue tissues using quantitative real-time PCR followed by
      statistical analysis. RESULTS: We found that the expression levels are
      significantly higher in malignant SCC than mild precancerous epithelial
      dysplasia, and the expression levels in general increase with increasing grade of
      precancerous lesions from mild, moderate to severe epithelial dysplasia. CDC6 and
      CDC45 expression is dependent of the dysplasia grade and lymph node status. CDT1
      expression is higher in severe dysplasia than in mild and moderate dysplasia.
      MCM2 expression is dependent of the dysplasia grade, lymph node status and
      clinical stage. The expression of the four genes is independent of tumor size or
      histological grade. A simple linear regression analysis revealed a linear
      increase in the mRNA levels of the four genes from the mild to severe dysplasia
      and SCC. A strong association was established between CDC6 and CDT1, and between
      MCM2 and CDC45 expression. The nonparametric receiver operating characteristic
      analysis suggested that MCM2 and CDC45 had a higher accuracy than CDC6 and CDT1
      for distinguishing dysplasia from tongue SCC. CONCLUSION: These proteins can be
      used as biomarkers to distinguish precancerous dysplasia from SCC and are useful
      for early detection and diagnosis of SCC as an adjunct to clinicopathological
      parameters.

PMID- 19116017
TI  - Folliculin mutations are not associated with severe COPD.
AB  - BACKGROUND: Rare loss-of-function folliculin (FLCN) mutations are the genetic
      cause of Birt-Hogg-Dube syndrome, a monogenic disorder characterized by
      spontaneous pneumothorax, fibrofolliculomas, and kidney tumors. Loss-of-function
      folliculin mutations have also been described in pedigrees with familial
      spontaneous pneumothorax. Because the majority of patients with folliculin
      mutations have radiographic evidence of pulmonary cysts, folliculin has been
      hypothesized to contribute to the development of emphysema. To determine whether
      folliculin sequence variants are risk factors for severe COPD, we genotyped seven
      previously reported Birt-Hogg-Dube or familial spontaneous pneumothorax
      associated folliculin mutations in 152 severe COPD probands participating in the
      Boston Early-Onset COPD Study. We performed bidirectional resequencing of all 14
      folliculin exons in a subset of 41 probands and subsequently genotyped four
      identified variants in an independent sample of345 COPD subjects from the
      National Emphysema Treatment Trial (cases) and 420 male smokers with normal lung
      function from the Normative Aging Study (controls). RESULTS: None of the seven
      previously reported Birt-Hogg-Dube or familial spontaneous pneumothorax mutations
      were observed in the 152 severe, early-onset COPD probands. Exon resequencing
      identified 31 variants, including two non-synonymous polymorphisms and two common
      non-coding polymorphisms. No significant association was observed for any of
      these four variants with presence of COPD or emphysema-related phenotypes.
      CONCLUSION: Genetic variation in folliculin does not appear to be a major risk
      factor for severe COPD. These data suggest that familial spontaneous pneumothorax
      and COPD have distinct genetic causes, despite some overlap in radiographic
      characteristics.

PMID- 19116019
TI  - Identification and management of adults with asthma prone to exacerbations: can
      we do better?
AB  - Exacerbations are a major cause of morbidity in asthma and generate high health
      costs. Identification and management of adults with asthma who are prone to
      exacerbations is of considerable importance as by this means it should be
      possible to reduce the number of patients who currently experience inadequately
      controlled disease. Exacerbations occur most frequently in individuals with
      severe disease. Other risk factors include a history of a recent exacerbation, co
      morbidities such as a raised body mass index and psychological problems as well
      as current smoking and lower socio-economic status. A low FEV1, particularly if
      combined with the additional information from questionnaires helps predict
      exacerbations. Despite the association between these risk factors and
      exacerbations it remains difficult to accurately predict in an individual patient
      with asthma whether they will go on to develop an exacerbation in the future. A
      major aim of international guidelines on the management of asthma is to prevent
      future risks of exacerbations, but some patients, particularly those with severe
      disease, respond poorly to current therapies and continue to experience recurrent
      exacerbations. There is an unmet need for improved management strategies and
      drugs targeted at preventing asthma exacerbations. Monitoring induced sputum
      eosinophil cell counts is helpful in preventing exacerbations in some patient
      with severe asthma. Future developments are likely to include the identification
      of better biomarkers to predict exacerbations or the cause of exacerbations,
      augmentation of the immunological response to viruses at the time of the
      exacerbation, the use of telemonitoring in patients with severe asthma and the
      development of improved therapies targeted at reducing exacerbations.

PMID- 19116020
TI  - Community health assessment using self-organizing maps and geographic information
      systems.
AB  - BACKGROUND: From a public health perspective, a healthier community environment
      correlates with fewer occurrences of chronic or infectious diseases. Our premise
      is that community health is a non-linear function of environmental and
      socioeconomic effects that are not normally distributed among communities. The
      objective was to integrate multivariate data sets representing social, economic,
      and physical environmental factors to evaluate the hypothesis that communities
      with similar environmental characteristics exhibit similar distributions of
      disease. RESULTS: The SOM algorithm used the intrinsic distributions of 92
      environmental variables to classify 511 communities into five clusters. SOM
      determined clusters were reprojected to geographic space and compared with the
      distributions of several health outcomes. ANOVA results indicated that the
      variability between community clusters was significant with respect to the
      spatial distribution of disease occurrence. CONCLUSION: Our study demonstrated a
      positive relationship between environmental conditions and health outcomes in
      communities using the SOM-GIS method to overcome data and methodological
      challenges traditionally encountered in public health research. Results
      demonstrated that community health can be classified using environmental
      variables and that the SOM-GIS method may be applied to multivariate
      environmental health studies.

PMID- 19116021
TI  - The effect of alternative permutation testing strategies on the performance of
      multifactor dimensionality reduction.
AB  - BACKGROUND: Multifactor Dimensionality Reduction (MDR) is a novel method
      developed to detect gene-gene interactions in case-control association analysis
      by exhaustively searching multi-locus combinations. While the end-goal of
      analysis is hypothesis generation, significance testing is employed to indicate
      statistical interest in a resulting model. Because the underlying distribution
      for the null hypothesis of no association is unknown, non-parametric permutation
      testing is used. Lately, there has been more emphasis on selecting all
      statistically significant models at the end of MDR analysis in order to avoid
      missing a true signal. This approach opens up questions about the permutation
      testing procedure. Traditionally omnibus permutation testing is used, where one
      permutation distribution is generated for all models. An alternative is n-locus
      permutation testing, where a separate distribution is created for each n-level of
      interaction tested. FINDINGS: In this study, we show that the false positive rate
      for the MDR method is at or below a selected alpha level, and demonstrate the
      conservative nature of omnibus testing. We compare the power and false positive
      rates of both permutation approaches and find omnibus permutation testing optimal
      for preserving power while protecting against false positives. CONCLUSION:
      Omnibus permutation testing should be used with the MDR method.

PMID- 19116022
TI  - Implementation of a national anti-tuberculosis drug resistance survey in
      Tanzania.
AB  - BACKGROUND: A drug resistance survey is an essential public health management
      tool for evaluating and improving the performance of National Tuberculosis
      control programmes. The current manuscript describes the implementation of the
      first national drug resistance survey in Tanzania. METHODS: Description of the
      implementation process of a national anti-tuberculosis drug resistance survey in
      Tanzania, in relation to the study protocol and Standard Operating Procedures.
      RESULTS: Factors contributing positively to the implementation of the survey were
      a continuous commitment of the key stakeholders, the existence of a well
      organized National Tuberculosis Programme, and a detailed design of cluster
      specific arrangements for rapid sputum transportation. Factors contributing
      negatively to the implementation were a long delay between training and actual
      survey activities, limited monitoring of activities, and an unclear design of the
      data capture forms leading to difficulties in form-filling. CONCLUSION: Careful
      preparation of the survey, timing of planned activities, a strong emphasis on
      data capture tools and data management, and timely supervision are essential for
      a proper implementation of a national drug resistance survey.

PMID- 19116023
TI  - Sudden loss of visual acuity following intra-articular steroid injection in to
      the knee joint: a case report.
AB  - BACKGROUND: Exogenous and endogenous steroids have been implicated in the
      pathogenesis of central serous choroioretinopathy in the literature. Central
      serous choroioretinopathy presents as sudden reduction in visual acuity. CASE
      PRESENTATION: Despite the fact that steroid injections are so commonly used in
      the Orthopaedics there is no information regarding central serous
      chorioretinopathy in Orthopaedic literature. We report a case of acute onset
      central serous chorioretinopathy following an intra-articular injection.
      CONCLUSION: Orthopaedic surgeons and doctors dealing with Musculoskeletal
      problems need to be aware of this unusual complication of systemic steroid
      therapy and refrain from administering further steroids to patients with history
      of blurring of vision or sudden loss of visual acuity following previous steroid
      injections.

PMID- 19116024
TI  - Large naturally-produced electric currents and voltage traverse damaged mammalian
      spinal cord.
AB  - BACKGROUND: Immediately after damage to the nervous system, a cascade of
      physical, physiological, and anatomical events lead to the collapse of neuronal
      function and often death. This progression of injury processes is called
      "secondary injury." In the spinal cord and brain, this loss in function and
      anatomy is largely irreversible, except at the earliest stages. We investigated
      the most ignored and earliest component of secondary injury. Large bioelectric
      currents immediately enter damaged cells and tissues of guinea pig spinal cords.
      The driving force behind these currents is the potential difference of adjacent
      intact cell membranes. For perhaps days, it is the biophysical events caused by
      trauma that predominate in the early biology of neurotrauma. RESULTS: An enormous
      (</= mA/cm2) bioelectric current transverses the site of injury to the mammalian
      spinal cord. This endogenous current declines with time and with distance from
      the local site of injury but eventually maintains a much lower but stable value
      (< 50 muA/cm2).The calcium component of this net current, about 2.0
      pmoles/cm2/sec entering the site of damage for a minimum of an hour, is
      significant. Curiously, injury currents entering the ventral portion of the
      spinal cord may be as high as 10 fold greater than those entering the dorsal
      surface, and there is little difference in the magnitude of currents associated
      with crush injuries compared to cord transection. Physiological measurements were
      performed with non-invasive sensors: one and two-dimensional extracellular
      vibrating electrodes in real time. The calcium measurement was performed with a
      self-referencing calcium selective electrode. CONCLUSION: The enormous
      bioelectric current, carried in part by free calcium, is the major initiator of
      secondary injury processes and causes significant damage after breach of the
      membranes of vulnerable cells adjacent to the injury site. The large intra
      cellular voltages, polarized along the length of axons in particular, are
      believed to be associated with zones of organelle death, distortion, and
      asymmetry observed in acutely injured nerve fibers. These data enlarge our
      understanding of secondary mechanisms and provide new ways to consider
      interfering with this catabolic and progressive loss of tissue.

PMID- 19116025
TI  - Sickle cell trait and priapism: a case report and review of the literature.
AB  - BACKGROUND: A 32 year-old African-American man presented to our institution after
      attempting suicide via ingestion with quetiapine. He had reported a history of
      several days of substance abuse with alcohol, cocaine and marijuana related to a
      partying binge. Following this, his partner removed him from his residence
      resulting in a suicide attempt. During hospitalization the patient developed
      priapism, a condition he had not experienced before. CASE PRESENTATION: Given
      this was his first time with priapism, an extensive work-up revealed the patient
      had previously undiagnosed sickle cell trait, which we postulate to have been a
      significant factor in his development of acute priapism. Sickle cell trait is
      considered to be a generally benign condition except for a few rare complications
      under more demanding physical conditions. However, upon reviewing the literature
      on the association of sickle cell trait with priapism, we believe this may not be
      the case. Case reports and small series that appeared in the 1960s and 1970s
      indicated an association between priapism and sickle trait. Little has been
      reported recently, and the general teaching regarding sickle cell trait does not
      include this information. However, one case was reported with the use of
      phosphodiesterase-5 (PDE-5) inhibitors and the development of priapism in a
      patient with sickle cell trait. These medications are now first line treatment in
      erectile dysfunction. They act by enhancing nitric oxide (NO) production leading
      to relaxation of smooth muscle in the corpora cavernosa and penile arteries.
      CONCLUSION: Priapism was not reported in the initial studies of these
      medications. Further review of the literature indicates this may be a complex
      relationship. Interestingly, PDE5 inhibitors also have been postulated to be
      protective in sickle cell disease and perhaps also sickle cell trait because
      priapism might be caused by reduced NO availability. In this article, we examine
      the evidence linking sickle cell trait to priapism, explore the implications of
      PDE5 use, particularly in the setting of sickle cell trait, and propose that
      teaching about sickle cell trait include a discussion of priapism risk.

PMID- 19116026
TI  - Quality of medical training and emigration of physicians from India.
AB  - BACKGROUND: Physician 'brain drain' negatively impacts health care delivery.
      Interventions to address physician emigration have been constrained by lack of
      research on systematic factors that influence physician migration. We examined
      the relationship between the quality of medical training and rate of migration to
      the United States and the United Kingdom among Indian medical graduates (1955
      2002). METHODS: We calculated the fraction of medical graduates who emigrated to
      the United States and the United Kingdom, based on rankings of medical colleges
      and universities according to three indicators of the quality of medical
      education (a) student choice, (b) academic publications, and (c) the availability
      of specialty medical training. RESULTS: Physicians from the top quintile medical
      colleges and of universities were 2 to 4 times more likely to emigrate to the
      United States and the United Kingdom than graduates from the bottom quintile
      colleges and universities. CONCLUSION: Graduates of institutions with better
      quality medical training have a greater likelihood of emigrating. Interventions
      designed to counter loss of physicians should focus on graduates from top quality
      institutions.

PMID- 19116027
TI  - Comparison between a linear versus a macrocyclic contrast agent for whole body MR
      angiography in a clinical routine setting.
AB  - BACKGROUND: Previous experiences of whole body MR angiography are predominantly
      available in linear 0.5 M gadolinium-containing contrast agents. The aim of this
      study was to compare image quality on a four-point scale (range 1-4) and
      diagnostic accuracy of a 1.0 M macrocyclic contrast agent (gadobutrol, n = 80
      patients) with a 0.5 M linear contrast agent (gadopentetate dimeglumine, n = 85
      patients) on a 1.5 T whole body MR system. Digital subtraction angiography served
      as standard of reference. RESULTS: All examinations yielded diagnostic image
      quality. There was no significant difference in image quality (3.76 +/- 0.3
      versus 3.78 +/- 0.3, p = n.s.) and diagnostic accuracy observed. Sensitivity and
      specificity of the detection of hemodynamically relevant stenoses was 93%/95% in
      the gadopentetate dimeglumine group and 94%/94% in the gadobutrol group,
      respectively. CONCLUSION: The high diagnostic accuracy of gadobutrol in the
      clinical routine setting is of high interest as medical authorities (e.g. the
      European Agency for the Evaluation of Medicinal Products) recommend macrocyclic
      contrast agents especially to be used in patients with renal failure or dialysis.

PMID- 19116029
TI  - A cryptic diagnosis: disseminated cryptococcal disease presenting as an
      asymptomatic pulmonary nodule and a skin lesion: a case report.
AB  - BACKGROUND: Cryptococcosis refers to a spectrum of infections caused by the
      encapsulated yeast Cryptococcus neoformans. In the immunocompromised host
      cryptococcus may disseminate resulting in significant mortality and morbidity.
      CASE PRESENTATION: We report the case of a 49-year-old homosexual male presenting
      with an atypical skin lesion associated with an asymptomatic pulmonary nodule. A
      subsequent diagnosis of disseminated cryptococcosis was made on India ink
      staining of cerebrospinal fluid. CONCLUSION: A diagnosis of cryptococcosis should
      be considered in all patients at risk of immunocompromise that present with
      asymptomatic pulmonary nodules in the presence of extrapulmonary manifestations,
      as exemplified by the unusual skin ulceration in our case.

PMID- 19116028
TI  - Expression of sterol regulatory element-binding transcription factor (SREBF) 2
      and SREBF cleavage-activating protein (SCAP) in human atheroma and the
      association of their allelic variants with sudden cardiac death.
AB  - BACKGROUND: Disturbed cellular cholesterol homeostasis may lead to accumulation
      of cholesterol in human atheroma plaques. Cellular cholesterol homeostasis is
      controlled by the sterol regulatory element-binding transcription factor 2 (SREBF
      2) and the SREBF cleavage-activating protein (SCAP). We investigated whole genome
      expression in a series of human atherosclerotic samples from different vascular
      territories and studied whether the non-synonymous coding variants in the
      interacting domains of two genes, SREBF-2 1784G>C (rs2228314) and SCAP 2386A>G,
      are related to the progression of coronary atherosclerosis and the risk of pre
      hospital sudden cardiac death (SCD). METHODS: Whole genome expression profiling
      was completed in twenty vascular samples from carotid, aortic and femoral
      atherosclerotic plaques and six control samples from internal mammary arteries.
      Three hundred sudden pre-hospital deaths of middle-aged (33-69 years) Caucasian
      Finnish men were subjected to detailed autopsy in the Helsinki Sudden Death
      Study. Coronary narrowing and areas of coronary wall covered with fatty streaks
      or fibrotic, calcified or complicated lesions were measured and related to the
      SREBF-2 and SCAP genotypes. RESULTS: Whole genome expression profiling showed a
      significant (p = 0.02) down-regulation of SREBF-2 in atherosclerotic carotid
      plaques (types IV-V), but not in the aorta or femoral arteries (p = NS for both),
      as compared with the histologically confirmed non-atherosclerotic tissues. In
      logistic regression analysis, a significant interaction between the SREBF-2
      1784G>C and the SCAP 2386A>G genotype was observed on the risk of SCD (p =
      0.046). Men with the SREBF-2 C allele and the SCAP G allele had a significantly
      increased risk of SCD (OR 2.68, 95% CI 1.07-6.71), compared to SCAP AA homologous
      subjects carrying the SREBF-2 C allele. Furthermore, similar trends for having
      complicated lesions and for the occurrence of thrombosis were found, although the
      results were not statistically significant. CONCLUSION: The results suggest that
      the allelic variants (SREBF-2 1784G>C and SCAP 2386A>G) in the cholesterol
      homeostasis regulating SREBF-SCAP pathway may contribute to SCD in early middle
      aged men.

PMID- 19116030
TI  - A simplified, robust, and streamlined procedure for the production of C. elegans
      transgenes via recombineering.
AB  - BACKGROUND: The nematode Caenorhabditis elegans has emerged as a powerful system
      to study biologic questions ranging from development to aging. The generation of
      transgenic animals is an important experimental tool and allows use of GFP fusion
      proteins to study the expression of genes of interest or generation of epitope
      tagged versions of specific genes. Transgenes are often generated by placing a
      promoter upstream of a reporter gene or cDNA. This often produces a
      representative expression pattern, but important exceptions have been observed.
      To better capture the genuine expression pattern and timing, several
      investigators have modified large pieces of DNA carried by BACs or fosmids for
      use in the construction of transgenic animals via recombineering. However, these
      techniques are not in widespread use despite the advantages when compared to
      traditional approaches. Additionally, some groups have encountered problems with
      employing these techniques. Hence, we sought identify ways to improve the
      simplicity and reliability of the procedure. RESULTS: We describe here several
      important modifications we have made to existing protocols to make the procedure
      simpler and more robust. Among these are the use of galK gene as a selection
      marker for both the positive and negative selection steps in recombineering, the
      use of R6K based plasmids which eliminate the need for extensive PCR product
      purification, a means to integrate the unc-119 marker on to the fosmid backbone,
      and placement of homology arms to commonly used GFP and TAP fusion genes flanking
      the galK cassette which reduces the cost of oligos by 50%. CONCLUSION: We have
      made several significant changes that allow the production of C. elegans
      transgenes from a commercially available fosmid library in a robust and
      streamlined manner. These changes make the technique more attractive especially
      to small academic labs unfamiliar with recombineering.

PMID- 19116031
TI  - Dermatitis associated with exposure to a marine cyanobacterium during
      recreational water exposure.
AB  - BACKGROUND: Anecdotal evidence reported an outbreak of symptoms on Fraser Island
      during the late 1990 s similar to those expected from exposure to dermotoxins
      found in the cyanobacterium L. majuscula. This coincided with the presence of a
      bloom of L. majuscula. METHODS: Records from the Fraser Island National Parks
      First aid station were examined. Information on cyanobacterial blooms at Fraser
      Island were obtained from Queensland National Parks rangers. RESULTS: Examination
      of first aid records from Fraser Island revealed an outbreak of symptoms
      predominantly in January and February 1998. CONCLUSION: During a bloom of L.
      majuscula there were numerous reports of symptoms that could be attributed to
      dermotoxins found in L. majuscula. The other four years examined had no L.
      majuscula blooms and the number of L. majuscula symptoms was much reduced. These
      cases comprised a high percentage of the cases treated at the first aid station.

PMID- 19116032
TI  - Role of spinal cord alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid
      receptors in complete Freund's adjuvant-induced inflammatory pain.
AB  - Spinal cord alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors
      (AMPARs) mediate acute spinal processing of nociceptive and non-nociceptive
      information, but whether and how their activation contributes to the central
      sensitization that underlies persistent inflammatory pain are still unclear.
      Here, we examined the role of spinal AMPARs in the development and maintenance of
      complete Freund's adjuvant (CFA)-induced persistent inflammatory pain.
      Intrathecal application of two selective non-competitive AMPAR antagonists, CFM-2
      (25 and 50 microg) and GYKI 52466 (50 microg), significantly attenuated
      mechanical and thermal hypersensitivities on the ipsilateral hind paw at 2 and 24
      h post-CFA injection. Neither CFM-2 nor GYKI 52466 affected the contralateral
      basal responses to thermal and mechanical stimuli. Locomotor activity was not
      altered in any of the drug-treated animals. CFA-induced inflammation did not
      change total expression or distribution of AMPAR subunits GluR1 and GluR2 in
      dorsal horn but did alter their subcellular distribution. The amount of GluR2 was
      markedly increased in the crude cytosolic fraction and decreased in the crude
      membrane fraction from the ipsilateral L4-5 dorsal horn at 24 h (but not at 2 h)
      post-CFA injection. Conversely, the level of GluR1 was significantly decreased in
      the crude cytosolic fraction and increased in the crude membrane fraction from
      the ipsilateral L4-5 dorsal horn at 24 h (but not at 2 h) post-CFA injection.
      These findings suggest that spinal AMPARs might participate in the central spinal
      mechanism of persistent inflammatory pain.

PMID- 19116034
TI  - Myofascial trigger points in cluster headache patients: a case series.
AB  - Active myofascial trigger points (MTrPs) have been found to contribute to chronic
      tension-type headache and migraine. The purpose of this case series was to
      examine if active trigger points (TrPs) provoking cluster-type referred pain
      could be found in cluster headache patients and, if so, to evaluate the
      effectiveness of active TrPs anaesthetic injections both in the acute and
      preventive headache's treatment. Twelve patients, 4 experiencing episodic and 8
      chronic cluster headache, were studied. TrPs were found in all of them. Abortive
      infiltrations could be done in 2 episodic and 4 chronic patients, and preemptive
      infiltrations could be done in 2 episodic and 5 chronic patients, both kind of
      interventions being successful in 5 (83.3%) and in 6 (85.7%) of the cases
      respectively. When combined with prophylactic drug therapy, injections were
      associated with significant improvement in 7 of the 8 chronic cluster patients.
      Our data suggest that peripheral sensitization may play a role in cluster
      headache pathophysiology and that first neuron afferent blockade can be useful in
      cluster headache management.

PMID- 19116033
TI  - A resampling-based meta-analysis for detection of differential gene expression in
      breast cancer.
AB  - BACKGROUND: Accuracy in the diagnosis of breast cancer and classification of
      cancer subtypes has improved over the years with the development of well
      established immunohistopathological criteria. More recently, diagnostic gene-sets
      at the mRNA expression level have been tested as better predictors of disease
      state. However, breast cancer is heterogeneous in nature; thus extraction of
      differentially expressed gene-sets that stably distinguish normal tissue from
      various pathologies poses challenges. Meta-analysis of high-throughput expression
      data using a collection of statistical methodologies leads to the identification
      of robust tumor gene expression signatures. METHODS: A resampling-based meta
      analysis strategy, which involves the use of resampling and application of
      distribution statistics in combination to assess the degree of significance in
      differential expression between sample classes, was developed. Two independent
      microarray datasets that contain normal breast, invasive ductal carcinoma (IDC),
      and invasive lobular carcinoma (ILC) samples were used for the meta-analysis.
      Expression of the genes, selected from the gene list for classification of normal
      breast samples and breast tumors encompassing both the ILC and IDC subtypes were
      tested on 10 independent primary IDC samples and matched non-tumor controls by
      real-time qRT-PCR. Other existing breast cancer microarray datasets were used in
      support of the resampling-based meta-analysis. RESULTS: The two independent
      microarray studies were found to be comparable, although differing in their
      experimental methodologies (Pearson correlation coefficient, R = 0.9389 and R =
      0.8465 for ductal and lobular samples, respectively). The resampling-based meta
      analysis has led to the identification of a highly stable set of genes for
      classification of normal breast samples and breast tumors encompassing both the
      ILC and IDC subtypes. The expression results of the selected genes obtained
      through real-time qRT-PCR supported the meta-analysis results. CONCLUSION: The
      proposed meta-analysis approach has the ability to detect a set of differentially
      expressed genes with the least amount of within-group variability, thus providing
      highly stable gene lists for class prediction. Increased statistical power and
      stringent filtering criteria used in the present study also make identification
      of novel candidate genes possible and may provide further insight to improve our
      understanding of breast cancer development.

PMID- 19116035
TI  - Transient midventricular ballooning: a case report and review of the literature.
AB  - BACKGROUND: We describe a case of transient left midventricular ballooning in 68
      year-old male patient presented with picture of acute coronary syndrome. CASE
      PRESENTATION: The left ventriculogram showed mid ventricular akinesis and
      dilatation along with hypercontractile apex and basal segments. Follow up
      echocardiogram after one month showed resolution of wall motions abnormalities
      and normalization of the left ventricular function. CONCLUSION: This is
      considered as a new variant of previously reported transient left ventricular
      apical ballooning; the only difference in our case is the location of wall
      motions abnormalities.

PMID- 19116036
TI  - Bilateral gluteal metastases from a misdiagnosed intrapelvic gastrointestinal
      stromal tumor.
AB  - BACKGROUND: The location of gastrointestinal stromal tumors (GIST) outside of the
      gastrointestinal system is a rare event. CASE PRESENTATION: A 56-year old woman
      presented with a GIST of the pelvis was misdiagnosed and treated as a uterine
      leiomyosarcoma. The diagnosis was made after the CD117 (KIT) positivity in the
      biopsy of the excised bowel mass four years from the first presentation. During
      this period she presented a bilateral muscle and subcutaneous metastasis in the
      gluteal area. CONCLUSION: The correct diagnosis of the extra-gastrointestinal
      stromal tumor is a challenge even for experienced pathologists. CD117 (KIT)
      positivity is the most important immunohistochemical feature in the histological
      diagnosis. To our knowledge a metastatic EGIST (extra-gastrointestinal stromal
      tumor) to the skeletal muscle bilaterally has not been described previously in
      the English medical literature.

PMID- 19116037
TI  - Gelatinase (MMP-2 and -9) expression profiles during gestation in the bovine
      endometrium.
AB  - BACKGROUND: Various molecules participate in implantation and maintaining
      endometrial function during gestation. The remodeling of endometrial matrices is
      a necessary process in the coordination of gestational progress. Matrix
      metalloproteinases (MMPs) like gelatinases (MMP-2 and -9) and collagenase (MMP-1)
      are considered to play important roles in this process. We examined MMP-2 and -9
      expression using zymography, in situ hybridization, real-time PCR, and microarray
      analysis to clarify their roles in the bovine endometrium during gestation.
      METHODS: Endometria, placentomes, and fetal membranes were collected from
      Japanese black cows that were killed on day 15 to 252 of gestation or during
      their estrous cycle. The gene expression of MMP-related molecules (mainly MMP-2
      and -9) was examined using a custom-made microarray, real-time RT-PCR, and in
      situ hybridization. Gelatinase activity was detected by zymography and film in
      situ zymography. RESULTS: Both gelatinases were expressed in the endometrium and
      fetal tissues throughout gestation. MMP-2 gene expression declined with the
      progress of gestation, but its intensity was maintained at a high level during
      the peri-implantation period and increased in late gestation. The expression
      level of MMP-9 was stably maintained, but was relatively low compared to that of
      MMP-2. These gene expression patterns matched those detected by zymography for
      the proteins. Microarray analysis suggested that the functions of MMP-2 during
      implantation and the last part of gestation are closely related with those of
      other molecules such as tissue inhibitors of metalloproteinase (TIMP)-2, a
      disintegrin and metalloproteinase with thrombospondin motifs (ADAMTS) 1, membrane
      type 1 (MT1)-MMP, and extracellular matrix metalloproteinase inducer (EMMPRIN).
      CONCLUSION: We detected MMP-2 and -9 gene expression in the bovine endometrium
      and placentome throughout gestation. These data suggest that MMP-2 is one of the
      main endometrial remodeling factors for implantation and pre-partum in cattle. In
      cows, as is the case in humans and rodents, gelatinases participate in
      endometrial remodeling, and their activities depend on the balance of activators
      and inhibitors; i.e., TIMP, MT-MMP, EMMPRIN, MMP-2, MMP-9, and so on.

PMID- 19116038
TI  - WSSV ie1 promoter is more efficient than CMV promoter to express H5 hemagglutinin
      from influenza virus in baculovirus as a chicken vaccine.
AB  - BACKGROUND: The worldwide outbreak of influenza A (H5N1) viruses among poultry
      species and humans highlighted the need to develop efficacious and safe vaccines
      based on efficient and scaleable production. RESULTS: White spot syndrome virus
      (WSSV) immediate-early promoter one (ie1) was shown to be a stronger promoter for
      gene expression in insect cells compared with Cytomegalovirus immediate-early
      (CMV) promoter in luciferase assays. In an attempt to improve expression
      efficiency, a recombinant baculovirus was constructed expressing hemagglutinin
      (HA) of H5N1 influenza virus under the control of WSSV ie1 promoter. HA
      expression in SF9 cells increased significantly with baculovirus under WSSV ie1
      promoter, compared with CMV promoter based on HA contents and hemagglutination
      activity. Further, immunization with baculovirus under WSSV ie1 promoter in
      chickens elicited higher level anti-HA antibodies compared to CMV promoter, as
      indicated in hemagglutination inhibition, virus neutralization and enzyme-linked
      immunosorbent assays. By immunohistochemistry, strong HA antigen expression was
      observed in different chicken organs with vaccination of WSSV ie1 promoter
      controlled baculovirus, confirming higher efficiency in HA expression by WSSV ie1
      promoter. CONCLUSION: The production of H5 HA by baculovirus was enhanced with
      WSSV ie1 promoter, especially compared with CMV promoter. This contributed to
      effective elicitation of HA-specific antibody in vaccinated chickens. This study
      provides an alternative choice for baculovirus based vaccine production.

PMID- 19116039
TI  - Microsatellite instability at a tetranucleotide repeat in type I endometrial
      carcinoma.
AB  - BACKGROUND: Microsatellite instability (MSI) at tri- or tetranucleotide repeat
      markers (elevated microsatellite alterations at selected tetranucleotide repeat,
      EMAST) has been recently described. But, the underlying genetic mechanism of
      EMAST is unclear. This study was to investigate the prevalence of EMAST, in type
      I endometrial carcinoma, and to determine the correlation between the MSI status
      and mismatch repair genes (MMR) or p53. METHODS: We examined the 3 mono-, 3 di-,
      and 6 tetranucleotide repeat markers by PCR in 39 cases of type I endometrial
      carcinoma and performed the immunohistochemistry of hMSH2, hMLH1, and p53
      protein. RESULTS: More than two MSI at mono- and dinucleotide repeat markers was
      noted in 8 cases (MSI-H, 20.5%). MSI, at a tetranucleotide repeat, was detected
      in 15 cases (EMAST, 38.5%). In remaining 16 cases, any MSI was not observed.
      (MSS, 42.1%), MSI status was not associated with FIGO stage, grade or depth of
      invasion. The absence of expression of either one of both hMSH2 or hMLH1 was
      noted in seven (87.5%) of eight MSI-H tumors, one (6.3%) of 16 MSS tumors, and
      five (33.3%) of 15 EMAST tumors. (p = 0.010) The expression of p53 protein was
      found in one (12.5%) of eight MSI-H tumors, five (31.3%) of 16 MSS tumors, and
      seven of 15 EMAST tumors. (p = 0.247) CONCLUSION: Our results showed that about
      38.5% of type I endometrial carcinomas exhibited EMAST, and that EMAST was rarely
      associated with alteration of hMSH2 or hMLH1.

PMID- 19116040
TI  - Detecting suicidality among adolescent outpatients: evaluation of trained
      clinicians' suicidality assessment against a structured diagnostic assessment
      made by trained raters.
AB  - BACKGROUND: Accurate assessment of suicidality is of major importance. We aimed
      to evaluate trained clinicians' ability to assess suicidality against a
      structured assessment made by trained raters. METHOD: Treating clinicians
      classified 218 adolescent psychiatric outpatients suffering from a depressive
      mood disorder into three classes: 1-no suicidal ideation, 2-suicidal ideation, no
      suicidal acts, 3-suicidal or self-harming acts. This classification was compared
      with a classification with identical content derived from the Kiddie Schedule for
      Affective Disorders and Schizophrenia (K-SADS-PL) made by trained raters. The
      convergence was assessed by kappa- and weighted kappa tests. RESULTS: The
      clinicians' classification to class 1 (no suicidal ideation) was 85%, class 2
      (suicidal ideation) 50%, and class 3 (suicidal acts) 10% concurrent with the K
      SADS evaluation (gamma2 = 37.1, df 4, p = 0.000). Weighted kappa for the
      agreement of the measures was 0.335 (CI = 0.198-0.471, p < 0.0001). The
      clinicians under-detected suicidal and self-harm acts, but over-detected suicidal
      ideation. CONCLUSION: There was only a modest agreement between the trained
      clinicians' suicidality evaluation and the K-SADS evaluation, especially
      concerning suicidal or self-harming acts. We suggest a wider use of structured
      scales in clinical and research settings to improve reliable detection of
      adolescents with suicidality.

PMID- 19116041
TI  - Past, present, and future of Japanese encephalitis.
AB  - Japanese encephalitis (JE), a vector-borne viral disease, is endemic to large
      parts of Asia and the Pacific. An estimated 3 billion people are at risk, and JE
      has recently spread to new territories. Vaccination programs, increased living
      standards, and mechanization of agriculture are key factors in the decline in the
      incidence of this disease in Japan and South Korea. However, transmission of JE
      is likely to increase in Bangladesh, Cambodia, Indonesia, Laos, Myanmar, North
      Korea, and Pakistan because of population growth, intensified rice farming, pig
      rearing, and the lack of vaccination programs and surveillance. On a global
      scale, however, the incidence of JE may decline as a result of large-scale
      vaccination programs implemented in China and India.

PMID- 19116042
TI  - Threat of dengue to blood safety in dengue-endemic countries.
AB  - Dengue, the most common arbovirus infection globally, is transmitted by mosquito
      vectors. Healthcare-related transmission, including transmission by blood
      products, has been documented, although the frequency of these occurrences is
      unknown. Dengue is endemic to Singapore, a city-state in Asia. Using mathematical
      modeling, we estimated the risk for dengue-infected blood transfusions in
      Singapore in 2005 to be 1.625-6/10,000 blood transfusions, assuming a ratio of
      asymptomatic to symptomatic infections of 2:1 to 10:1. However, the level of
      viremia required to cause clinical dengue cases is person-dependent and unknown.
      Further studies are needed to establish the magnitude of the threat that dengue
      poses to blood safety in countries where it is endemic. It will then be possible
      after this information is obtained to assess whether screening is feasible and to
      identify approaches that are most cost-effective on the basis of characteristics
      of local populations and seasonality of dengue.

PMID- 19116043
TI  - Sphingomonas paucimobilis bloodstream infections associated with contaminated
      intravenous fentanyl.
AB  - Nationally distributed medications from compounding pharmacies, which typically
      adhere to less stringent quality-control standards than pharmaceutical
      manufacturers, can lead to multistate outbreaks. We investigated a cluster of 6
      patients in a Maryland hospital who had Sphingomonas paucimobilis bloodstream
      infections in November 2007. Of the 6 case-patients, 5 (83%) had received
      intravenous fentanyl within 48 hours before bacteremia developed. Cultures of
      unopened samples of fentanyl grew S. paucimobilis; the pulsed-field gel
      electrophoresis pattern was indistinguishable from that of the isolates of 5 case
      patients. The contaminated fentanyl lot had been prepared at a compounding
      pharmacy and distributed to 4 states. Subsequently, in California, S.
      paucimobilis bacteremia was diagnosed for 2 patients who had received intravenous
      fentanyl from the same compounding pharmacy. These pharmacies should adopt more
      stringent quality-control measures, including prerelease product testing, when
      compounding and distributing large quantities of sterile preparations.

PMID- 19116044
TI  - Human infection with highly pathogenic avian influenza virus (H5N1) in northern
      Vietnam, 2004-2005.
AB  - We performed a retrospective case-series study of patients with influenza A
      (H5N1) admitted to the National Institute of Infectious and Tropical Diseases in
      Hanoi, Vietnam, from January 2004 through July 2005 with symptoms of acute
      respiratory tract infection, a history of high-risk exposure or chest
      radiographic findings such as pneumonia, and positive findings for A/H5 viral RNA
      by reverse transcription-PCR. We investigated data from 29 patients (mean age
      35.1 years) of whom 7 (24.1%) had died. Mortality rates were 20% (5/25) and 50%
      (2/4) among patients treated with or without oseltamivir (p = 0.24),
      respectively, and were 33.3% (5/15) and 14.2% (2/14) among patients treated with
      and without methylprednisolone (p = 0.39), respectively. After exact logistic
      regression analysis was adjusted for variation in severity, no significant
      effectiveness for survival was observed among patients treated with oseltamivir
      or methylprednisolone.

PMID- 19116045
TI  - Enhanced hygiene measures and norovirus transmission during an outbreak.
AB  - Control of norovirus outbreaks relies on enhanced hygiene measures, such as
      handwashing, surface cleaning, using disposable paper towels, and using separate
      toilets for sick and well persons. However, little is known about their
      effectiveness in limiting further spread of norovirus infections. We analyzed
      norovirus outbreaks in 7 camps at an international scouting jamboree in the
      Netherlands during 2004. Implementation of hygiene measures coincided with an
      84.8% (95% predictive interval 81.2%-86.6%) reduction in reproduction number.
      This reduction was unexpectedly large but still below the reduction needed to
      contain a norovirus outbreak. Even more stringent control measures are required
      to break the chain of transmission of norovirus.

PMID- 19116047
TI  - Venetian rule and control of plague epidemics on the Ionian Islands during 17th
      and 18th centuries.
AB  - During the 17th and 18th centuries, measures were taken by the Venetian
      administration to combat plague on the Ionian Islands. At that time, although the
      scientific basis of plague was unknown, the Venetians recognized its infectious
      nature and successfully decreased its spread by implementing an information
      network. Additionally, by activating a system of inspection that involved
      establishing garrisons along the coasts, the Venetians were able to control all
      local movements in plague-infested areas, which were immediately isolated. In
      contrast, the neighboring coast of mainland Greece, which was under Ottoman rule,
      was a plague-endemic area during the same period. We conclude that even in the
      absence of scientific knowledge, close observation and social and political
      measures can effectively restrain infectious outbreaks to the point of
      disappearance.

PMID- 19116046
TI  - Selection tool for foodborne norovirus outbreaks.
AB  - Detection of pathogens in the food chain is limited mainly to bacteria, and the
      globalization of the food industry enables international viral foodborne
      outbreaks to occur. Outbreaks from 2002 through 2006 recorded in a European
      norovirus surveillance database were investigated for virologic and epidemiologic
      indicators of food relatedness. The resulting validated multivariate logistic
      regression model comparing foodborne (n = 224) and person-to-person (n = 654)
      outbreaks was used to create a practical web-based tool that can be limited to
      epidemiologic parameters for nongenotyping countries. Non-genogroup-II.4
      outbreaks, higher numbers of cases, and outbreaks in restaurants or households
      characterized (sensitivity = 0.80, specificity = 0.86) foodborne outbreaks and
      reduced the percentage of outbreaks requiring source-tracing to 31%. The
      selection tool enabled prospectively focused follow-up. Use of this tool is
      likely to improve data quality and strain typing in current surveillance systems,
      which is necessary for identification of potential international foodborne
      outbreaks.

PMID- 19116048
TI  - Parapneumonic empyema deaths during past century, Utah.
AB  - Bacterial pneumonia with empyema is a serious complication of influenza and
      commonly resulted in death during the 1918 influenza pandemic. We hypothesize
      that deaths caused by parapneumonic empyema are increasing in Utah once again
      despite advances in critical care and the availability of antimicrobial drugs and
      new vaccines. In this study, we analyzed the historical relationship between
      deaths caused by empyema and influenza pandemics by using 100 years of data from
      Utah. Deaths caused by empyema have indeed increased from 2000-2004 when compared
      with the historic low death rates of 1950-1975. Vaccine strategies and
      antimicrobial drug stockpiling to control empyema will be important as we prepare
      for the next influenza pandemic.

PMID- 19116049
TI  - Microsporidiosis and malnutrition in children with persistent diarrhea, Uganda.
AB  - We show that the microsporidian fungus Enterocytozoon bieneusi is associated with
      lower rates of weight gain in children in Uganda with persistent diarrhea. This
      relationship remained after controlling for HIV and concurrent cryptosporidiosis.
      Children with microsporidiosis were predicted to weigh 1.3 kg less than children
      without microsporidiosis at 5 years of age.

PMID- 19116050
TI  - Invasive disease caused by nontuberculous mycobacteria, Tanzania.
AB  - Data on nontuberculous mycobacterial (NTM) disease in sub-Saharan Africa are
      limited. During 2006-2008, we identified 3 HIV-infected patients in northern
      Tanzania who had invasive NTM; 2 were infected with "Mycobacterium sherrisii" and
      1 with M. avium complex sequevar MAC-D. Invasive NTM disease is present in HIV
      infected patients in sub-Saharan Africa.

PMID- 19116051
TI  - Experimental infection of dogs with avian-origin canine influenza A virus (H3N2).
AB  - Susceptible dogs were brought into contact with dogs experimentally infected with
      an avian-origin influenza A virus (H3N2) that had been isolated from a pet dog
      with severe respiratory syndrome. All the experimentally infected and contact
      exposed dogs showed elevated rectal temperatures, virus shedding, seroconversion,
      and severe necrotizing tracheobronchitis and bronchioalveolitis.

PMID- 19116052
TI  - Personal protective equipment and risk for avian influenza (H7N3).
AB  - An outbreak of avian influenza (H7N3) among poultry resulted in laboratory
      confirmed disease in 1 of 103 exposed persons. Incomplete use of personal
      protective equipment (PPE) was associated with conjunctivitis and influenza-like
      symptoms. Rigorous use of PPE by persons managing avian influenza outbreaks may
      reduce exposure to potentially hazardous infected poultry materials.

PMID- 19116053
TI  - Imported case of poliomyelitis, Melbourne, Australia, 2007.
AB  - Wild poliovirus-associated paralytic poliomyelitis has not been reported in
      Australia since 1977. We report type 1 wild poliovirus infection in a man who had
      traveled from Pakistan to Australia in 2007. Poliomyelitis should be considered
      for patients with acute flaccid paralysis or unexplained fever who have been to
      poliomyelitis-endemic countries.

PMID- 19116054
TI  - Isolation of Candidatus Bartonella melophagi from human blood.
AB  - Candidatus Bartonella melophagi was isolated by blood culture from 2 women, 1 of
      whom was co-infected with B. henselae. Partial 16S rRNA, RNA polymerase B, and
      citrate synthase genes and 16S-23S internal transcribed spacer sequences
      indicated that human isolates were similar to Candidatus B. melophagi.

PMID- 19116055
TI  - Botulism from drinking pruno.
AB  - Foodborne botulism occurred among inmates at 2 prisons in California in 2004 and
      2005. In the first outbreak, 4 inmates were hospitalized, 2 of whom required
      intubation. In the second event, 1 inmate required intubation. Pruno, an
      alcoholic drink made illicitly in prisons, was the novel vehicle for these cases.

PMID- 19116056
TI  - Isolation of Bordetella avium and novel Bordetella strain from patients with
      respiratory disease.
AB  - Bordetella avium is thought to be strictly an avian pathogen. However, 16S rRNA
      gene sequencing identified 2 isolates from 2 humans with respiratory disease as
      B. avium and a novel B. avium-like strain. Thus, B. avium and B. avium-like
      organisms are rare opportunistic human pathogens.

PMID- 19116057
TI  - Clonal multidrug-resistant Corynebacterium striatum strains, Italy.
AB  - We assessed the clinical relevance and performed molecular characterization of 36
      multidrug-resistant strains of Corynebacterium striatum. Pulsed-field gel
      electrophoresis confirmed a single clone, possessing erm(X), tetA/B, cmxA/B, and
      aphA1 genes, but few related subclones. This strain is emerging as a pathogen in
      Italy.

PMID- 19116058
TI  - Enterovirus 71 outbreak, Brunei.
AB  - Enterovirus 71 (EV71) outbreaks occur periodically in the Asia-Pacific region. In
      2006, Brunei reported its first major outbreak of EV71 infections, associated
      with fatalities from neurologic complications. Isolated EV71 strains formed a
      distinct lineage with low diversity within subgenogroup B5, suggesting recent
      introduction and rapid spread within Brunei.

PMID- 19116059
TI  - Novel human rotavirus genotype G5P[7] from child with diarrhea, Cameroon.
AB  - We report characterization of a genotype G5P[7] human rotavirus (HRV) from a
      child in Cameroon who had diarrhea. Sequencing of all 11 gene segments showed
      similarities to > or =5 genes each from porcine and human rotaviruses. This
      G5P[7] strain exemplifies the importance of heterologous animal rotaviruses in
      generating HRV genetic diversity through reassortment.

PMID- 19116060
TI  - Serotype g12 rotaviruses, Lilongwe, Malawi.
AB  - To assess diversity of rotavirus strains in Lilongwe, Malawi, we conducted a
      cross-sectional study of children with acute gastroenteritis, July 2005-June
      2007. Serotype G12 was identified in 30 (5%) of 546 rotavirus-positive fecal
      specimens. The G12 strain possessed multiple electropherotypes and P-types, but
      their viral protein 7 sequences were closely related, indicating that
      reassortment has occurred.

PMID- 19116061
TI  - G2 strain of rotavirus among infants and children, Bangladesh.
AB  - To determine G and P genotypes, we performed nested PCR on 307 rotavirus
      specimens collected in Dhaka, Bangladesh, during 2004-2005. G2 (43.3%) was
      detected at the highest frequency, followed by G4 (19.5%), G9 (13.7%), G1
      (12.7%), and G3 (2.6%). P[8] was the most predominant genotype (53.2%), followed
      by P[4] (42.9%).

PMID- 19116062
TI  - Rotavirus genotype distribution after vaccine introduction, Rio de Janeiro,
      Brazil.
AB  - Brazil introduced rotavirus vaccination in March 2006. We studied 133 rotavirus
      positive fecal samples collected from February 2005 through December 2007.
      Genotype G2P[4] was found in 1.4% of samples in 2005, in 44% in 2006, and in 96%
      in 2007. Rotavirus detection rate decreased from 38% in 2005 to 24% in 2007 (p =
      0.012).

PMID- 19116063
TI  - Rickettsia helvetica in Dermacentor reticulatus ticks.
AB  - We report on the molecular evidence that Dermacentor reticulatus ticks in Croatia
      are infected with Rickettsia helvetica (10%) or Rickettsia slovaca (2%) or co
      infected with both species (1%). These findings expand the knowledge of the
      geographic distribution of R. helvetica and D. reticulatus ticks.

PMID- 19116064
TI  - Variation in Antimicrobial resistance in sporadic and outbreak-related Salmonella
      enterica serovar Typhimurium.
AB  - The prevalence of different antimicrobial resistance profiles and variants of the
      Salmonella genomic island 1 (SGI1) was reported for Salmonella enterica serovar
      Typhimurium DT104 strains isolated from patients in Denmark. Variation in
      antimicrobial resistance and corresponding changes of SGI1 were shown among
      isolates from a foodborne outbreak.

PMID- 19116065
TI  - Predicting high risk for human hantavirus infections, Sweden.
AB  - An increased risk for hemorrhagic fever with renal syndrome caused by Puumala
      hantavirus was forecast for Sweden in 2007. The forecast was based on a predicted
      increase in the number of Myodes glareolus rodents (reservoir hosts). Despite
      raised awareness and preparedness, the number of human cases during July 2007
      June 2008 was 1,483, a new high.

PMID- 19116066
TI  - Polyomaviruses KI and WU in immunocompromised patients with respiratory disease.
AB  - Polyomaviruses KI (KIPyV) and WU (WUPyV) were recently identified, mainly in
      respiratory specimens from children. Among 200 patients with respiratory
      disorders admitted to Saint Louis Hospital, Paris, France, KIPyV was detected in
      8% and WUPyV in 1%. KIPyV was significantly more frequent among human stem cell
      transplant patients (17.8% vs. 5.1%; p = 0.01).

PMID- 19116068
TI  - Falciparum malaria in patient 9 years after leaving malaria-endemic area.

PMID- 19116067
TI  - Hepatitis E virus genotype 3 diversity, France.
AB  - We characterized 42 hepatitis E virus (HEV) genotype 3 strains from infected
      patients in France in 3 parts of the genome and sequenced the full-length HEV
      genotype 3f genome found in Europe. These strains are closely related to swine
      strains in Europe, which suggests zoonotic transmission of HEV in France.

PMID- 19116069
TI  - Linezolid-resistant Staphylococcus cohnii, Greece.

PMID- 19116070
TI  - Buruli ulcer in long-term traveler to Senegal.

PMID- 19116071
TI  - Evidence of maternal-fetal transmission of Parachlamydia acanthamoebae.

PMID- 19116072
TI  - Emerging Mycobacteria spp. in cooling towers.

PMID- 19116073
TI  - Clostridium difficile-related hospitalizations among US adults, 2006.

PMID- 19116074
TI  - Pulmonary tuberculosis and Mycobacterium bovis, Uganda.

PMID- 19116075
TI  - Vertical transmission of Pneumocystis jirovecii in humans.

PMID- 19116076
TI  - Avian influenza virus (H5N1) in human, Laos.

PMID- 19116077
TI  - Fatal HIV encephalitis in HIV-seronegative patients.

PMID- 19116078
TI  - Classical ctxB in Vibrio cholerae O1, Kolkata, India.

PMID- 19116079
TI  - Sphingomonas mucosissima Bacteremia in patient with sickle cell disease.

PMID- 19116080
TI  - WU polyomavirus in fecal specimens of children with acute gastroenteritis, China.

PMID- 19116081
TI  - SCCmec typing in methicillin-resistant Staphylococcus aureus strains of animal
      origin.

PMID- 19116083
TI  - Traveling light and the tyranny of higher expectations.
AB  - "Three tribes of Babylonians," Herodotus wrote, "eat nothing but fish, which they
      catch and dry in the sun. They pound the dried fish in a mortar with a pestle and
      sift through a cloth then mix with liquid and bake like bread." Such are their
      customs, he reported, "Having no physicians, they bring the sick to the agora to
      receive advice from passers-by who have similar ailments."

PMID- 19116082
TI  - School closure to reduce influenza transmission.

PMID- 19116084
TI  - cDNA sequencing and expression analysis of Dicentrarchus labrax heme oxygenase-1.
AB  - The liver cDNA encoding heme oxygenase--1 (HO-1) was sequenced from European sea
      bass (Dicentrarchus labrax) (accession number no. EF139130). The HO-1 cDNA was
      1250 bp in nucleotide length and the open reading frame encoded 277 amino acid
      residues. The deduced amino acid sequence of the European sea bass had 75% and
      50% identity with the amino acid sequences of tetraodontiformes (Tetraodon
      nigroviridis and Takifugu rubripes) and human HO-1 proteins, respectively. A
      short hydrophobic transmembrane domain at the C--terminal region was found, and
      four histidine residues were highly conserved, including human his25 that is
      essential for HO catalytic activity. RT-PCR of mRNA from eight different European
      sea bass tissues revealed that, in a homeostatis state, the heme oxygenase--1 was
      abundant in the spleen and liver but not in the brain.

PMID- 19116085
TI  - Edible mushroom Agaricus sylvaticus can prevent the onset of atheroma plaques in
      hipercholesterolemic rabbits.
AB  - Since the involvement of free radicals in the pathophysiology of atherosclerosis
      was proposed, antioxidant supplementation arose as a potential strategy for the
      management of this disease. Thus, we decided to investigate the potential benefit
      of a natural antioxidant--rich edible mushroom (Agaricus sylvaticus) on the
      prevention of atherosclerosis. New Zealand rabbits underwent atherosclerosis
      induction by feeding a cholesterol--enriched chow (Group A), while Group B
      simultaneously received edible mushroom A. sylvaticus water solution. Control
      group received standard rabbit chow only (Group C). At the end of 10 week
      treatment period serum samples were drawn for lipid profile, uric acid,
      thiobarbituric acid reactive substances (TBARS), and total antioxidant status
      (TAS). The area of aorta arteries taken by atheroma plaques was evaluated. Groups
      A and B presented higher cholesterol levels (p< 0.01) and reduced TAS (p<0.01),
      when compared to the Group C. However, TBARS and uric acid levels for Group B
      animals' were reduced, in comparison to Group A (p<0.05), and equals to group C.
      Moreover, animals from group A developed extensive atherosclerotic areas (47.0+/
      14.0%), and that was prevented by the supplementation of A. sylvaticus (6.6+/
      2.9%, p<0.01). Data suggested that A. sylvaticus can prevent the development of
      atherosclerosis in spite of hipercholesterolemia.

PMID- 19116086
TI  - Prognosis of human liver transplantation.
AB  - The results of publications on liver transplantation were diverse since several
      years, without model prognosis. The impossibility was due to the international
      system of measurement. We resorted to vector functions for calculating the ratios
      of biological values. We studied 2 samples with the same total number (35
      patients) in the same conditions. We proposed 2 vector functions of transplants:
      (alpha)v1 weight/age donor and recipient in proportion to obtain a medium
      coefficient; (gamma)v2 ratio of biliary volume/700 mL (minimum secretion); beta
      was the coefficient of ratio ALT/AST (transaminases). After evaluation of 560
      observations and mathematical control about 3000 numbers, we compared the samples
      with 10 parameters without significant difference between variances, means, other
      values; with consented errors alpha= beta = 0.05; gamma < 10(-7); means of
      relative errors = +/- 0.03 negligible. The results were verified by diverse tests
      (standard deviation of differences, chi2-test, relative risk, odds ratio,
      comparisons of distributions, parent population, equations of normality, partial
      correlations, partial regression coefficients, multiple regression, coefficient
      beta. Final results : quantitative prognosis by grading ; right responders to
      immunosuppressive treatment without complications, RR1 fast response (scores 3.5
      ; 4) ; RR2 slow response (scores 2 ; 2.5 ; 3). Partial responders: very slow
      response (score 2; 2.5; 3) with transitory complications. Those patients were in
      recovery (81.5c/o). Wrong responders (score 2), 4 deaths (5.55c/o) by ARS; score
      2.5, 1 death (1.5 5c/o) by ARS. We subtracted beta from these scores to
      differentiate them. Non-responders (score 1.5), 2 deaths (35c/o) by ARS.

PMID- 19116087
TI  - Incomplete prostatectomy for cancer.

PMID- 19116089
TI  - A randomized placebo-controlled study of the efficacy of antimuscarinics in the
      treatment of pediatric overactive bladder and incontinence.

PMID- 19116088
TI  - Circulating tumor cells as a potential efficacy end point in clinical trials of
      hormone-resistant prostate cancer.

PMID- 19116090
TI  - Approach to the small renal mass: weighing treatment options.
AB  - The increased detection of incidental renal masses has introduced new challenges
      into the management of patients with newly discovered renal masses. Much interest
      has been focused on the diagnostic accuracy and the prognostic ability of imaging
      studies. These studies have elucidated trends that can guide management but
      remain woefully inaccurate for predicting the exceptions to the rule, many of
      which can produce untoward outcomes. Renal biopsy may aid in the management of
      patients with indeterminate -imaging; however, the role of biomarkers remains
      unclear. Active surveillance has emerged as an attractive option in certain
      patient populations, although the lack of reliable predictors of tumor behavior
      based upon currently available surveillance techniques understandably raises
      concerns about its propriety. For patients who would benefit from operative
      management, nephron-sparing procedures such as ablation and partial nephrectomy
      have gained increasing acceptance as an alternative to radical nephrectomy.

PMID- 19116091
TI  - The impact of renal surgery on global renal function and non-oncologic morbidity.
AB  - Nephron preservation has been increasingly prioritized in the treatment of small
      renal tumors. Radical nephrectomy is now understood as a risk factor for
      development of chronic kidney disease, which is known to increase the risk of
      cardiovascular events and all-cause mortality. Indications for nephron-sparing
      surgery (NSS) have broadened from solitary kidney, bilateral tumors, and
      hereditary tumor syndromes to essentially all small renal tumors. Laparoscopic
      NSS has demonstrated excellent cancer control as well as good functional
      preservation despite the need for warm ischemia. There has been ongoing debate
      regarding safe parameters for warm ischemia, which are thought to vary with
      patient factors. Focal ablative therapies have been developed for use in high
      risk surgical candidates (eg, radiofrequency ablation, cryoablation) to minimize
      renal and other treatment-related morbidity. Emphasis on minimally invasive
      approaches and advances in preventing renal dysfunction and other morbidity after
      NSS will guide the future of these therapies.

PMID- 19116092
TI  - Surgical options in the management of ureteropelvic junction obstruction.
AB  - Ureteropelvic junction obstruction (UPJO) is a common cause of upper urinary
      tract obstruction that can be clinically silent or lead to symptoms such as pain,
      chronic urinary tract infections, and urinary stone disease. UPJO does not always
      mandate treatment, but when an indication for correction is present, there are
      several minimally invasive surgical options available. Surgical reconstruction
      represents the gold-standard treatment for UPJO, although endoscopic pyelotomy is
      a well established and efficacious alternative.

PMID- 19116093
TI  - Medical therapy of stone disease: from prevention to promotion of passage
      options.
AB  - Medical therapy has been used for many years in the prevention of urinary stones.
      Medications directed at correcting urinary metabolic abnormalities responsible
      for promoting stone formation include thiazide diuretics, citrate salts, and
      allopurinol. All have proven to be efficacious. In addition, intake of citrate
      rich juices, such as lemonade, may help to reduce urinary stone formation. More
      recently, there has been increasing interest in and use of medical therapy to
      aide in the passage of ureteral stones. Medical expulsive therapy (MET) has been
      shown to be cost effective compared with observation followed by treatment. Alpha
      adrenergic receptor blockers are most commonly prescribed to promote passage of
      ureteral stones. They are able to facilitate stone passage, reduce time to
      passage, and decrease pain. Calcium-channel blockers also increase stone-passage
      rates. Steroids are useful adjuncts in MET.

PMID- 19116094
TI  - Integration of surgery and systemic therapy in the management of metastatic renal
      cancer.
AB  - Integration of surgery and systemic therapies represents the best management
      option for most patients with metastatic renal cell carcinoma. Cytoreductive
      nephrectomy, metastasectomy, and consolidative surgery can all play a vital role
      in this challenging patient population. Relevant issues in this era relate to the
      timing of surgery, the role of cytoreduction as systemic therapies become more
      effective, management of the residual mass, and surgical safety after targeted
      therapy.

PMID- 19116095
TI  - Robotic and laparoscopic radical cystectomy in the management of bladder cancer.
AB  - To review the current status of robot-assisted and laparoscopic radical
      cystectomy (RARC and LRC) in the management of bladder cancer, published English
      literature was searched using the National Library of Medicine database. The
      experience with RARC is rapidly growing, and this minimally invasive option and
      has relatively better results than LRC. Both techniques allow an appropriate
      lymph node dissection in the hands of experienced and skilled surgeons at high
      volume centers. The early and intermediate oncological outcomes of RARC and LRC
      compare favorably with open radical cystectomy (ORC). Extracorporeal urinary
      diversions are performed via a mini-incision in most cases and have better
      outcome than pure intracorporeal urinary diversions. RARC has taken over LRC at
      most of the centers where robot is available. The future of RARC with
      extracorporeal urinary diversion looks optimistic and has potential to supplant
      ORC, but with greater cost.

PMID- 19116096
TI  - Robotic pyeloplasty in the pediatric population.
AB  - The procedure most performed with the da Vinci system (Intuitive Surgical,
      Sunnyvale, CA) in pediatric urology is pyeloplasty for ureteropelvic junction
      obstruction. As with laparoscopic pyeloplasty, robotic-assisted pyeloplasty (RAP)
      can be performed by a trans- or retroperitoneal approach. Suturing is done with a
      6-0 monofilament absorbable suture, but any 5-0 or 6-0 suture can be used
      depending on the size of the patient. Currently, it appears that nothing larger
      than 6-0 is recommended for small children and infants. RAP in children has been
      demonstrated to be feasible and to have satisfactory results. Although there are
      only a few published series on the long-term outcome to date, the short-term data
      suggest that outcomes are similar to those of open pyeloplasty in children, and
      it appears to be more than promising.

PMID- 19116097
TI  - Fiberoptic imaging for urologic surgery.
AB  - Laparoscopic and robot-assisted surgery is likely to be improved with the
      development of real-time, intraoperative imaging for diagnosis, margin
      determination, and anatomical definition. A significant goal of much of this
      effort has been focused upon providing better outcomes after radical
      prostatectomy. The feasibility of fluorescent imaging of labeled cavernosal
      nerves in the operative field has been demonstrated in vivo in animals. Other
      applications of the technology and capability will certainly be developed over
      time. This article reviews and assesses the potential and capabilities of the
      different imaging modes currently in use or development.

PMID- 19116099
TI  - Needlescopic ablation of small adrenal masses.
AB  - Needlescopic adrenal ablative therapy is an attractive therapeutic option for the
      management of small adrenal masses. The spectrum of neoplasms that can be ablated
      includes isolated solid organ metastases (lung, kidney, liver), nonisolated but
      symptomatic (painful) adrenal metastasis, and small, nonmetastatic, hormonally
      active adrenal tumors. Moreover, needlescopic ablation offers an effective
      minimally morbid intervention for patients who are poor surgical candidates
      either due to advanced age and/or significant comorbid conditions. Ablative
      techniques described to date include radiofrequency ablation (RFA), cryoablation,
      and chemical ablation. Most procedures can be performed under percutaneous
      radiographic guidance on an outpatient basis. By and large, the bulk of clinical
      experience with adrenal ablation pertains to RFA. Successful ablation is usually
      dependent upon lesion size, with tumors 5 cm or smaller demonstrating the highest
      successful ablation rates. The most frequently described adverse sequelae of
      adrenal ablation are local tumor recurrences. However, many of these local
      recurrences can be managed by repeat ablation, with patients demonstrating
      durable oncologic outcomes.

PMID- 19116098
TI  - Surgical management of metastases to the adrenal gland: open, laparoscopic, and
      ablative approaches.
AB  - The adrenal gland is a potential site of metastasis for various malignancies.
      Metastases to the adrenal gland are the second most common type of adrenal mass
      lesion after adenomas. Differentiation of a metastatic lesion from a primary
      adrenal lesion can be challenging and requires the selective use of radiologic
      imaging, serologic testing, and adrenal biopsy. In patients who present with an
      isolated adrenal metastasis, adrenalectomy is often considered to aid in cancer
      control. Numerous studies have reported improved survival with resection of
      solitary adrenal metastases for various types of primary tumors. Traditionally,
      open adrenalectomy was the preferred option for these patients. More recently,
      laparoscopic adrenalectomy has offered a minimally invasive approach, with its
      resultant advantages of improved perioperative parameters. Proper patient
      selection for the laparoscopic versus open approach remains paramount in deciding
      the best treatment for the individual patient.

PMID- 19116100
TI  - Clinical update on the management of adrenal hemorrhage.
AB  - Adrenal hemorrhage is a rare yet potentially life-threatening event that occurs
      both in traumatic conditions and in a variety of nontraumatic conditions.
      Clinical manifestations of adrenal hemorrhage can vary widely depending on the
      degree and rate of hemorrhage, as well as the amount of adrenal cortex
      compromised by hemorrhage. Although an isolated focal unilateral adrenal
      hemorrhage may present subclinically, massive bilateral adrenal hemorrhage may
      lead to rapid cardiovascular collapse and ultimately death if not diagnosed
      appropriately and treated quickly. Diagnosis of adrenal hemorrhage is often
      complicated by its nonspecific presentation and tendency to occur in the setting
      of acute illness and other complicating medical conditions. This article outlines
      the variety of clinical situations in which adrenal hemorrhage can occur,
      summarizes the appropriate diagnostic tests available, and reviews the
      appropriate management of adrenal hemorrhage.

PMID- 19116101
TI  - [Access to treatment of HIV/AIDS in the South: the challenges of sustainability].

PMID- 19116102
TI  - [VGLUT3, an unsuspected agent of striatal cholinergic transmission].

PMID- 19116103
TI  - [Polyoxometalates. A new class of inorganic CK2 inhibitors].

PMID- 19116104
TI  - [The mapping of numbers on space: evidence for an original logarithmic
      intuition].

PMID- 19116105
TI  - [Preeclampsia].

PMID- 19116106
TI  - [Dynamic analysis of cell signalling: the example of the Saccharomyces cerevisiae
      osmotic response].

PMID- 19116107
TI  - [Hepatitis E: from zoonotic transmission to chronic infection in immunosuppressed
      patients].

PMID- 19116108
TI  - [Role of the cadherin Celsr3 in the connectivity of the cerebral cortex].

PMID- 19116109
TI  - [A novel mechanism by which reward and drugs of abuse alter chromatin in
      neurons].

PMID- 19116110
TI  - [Carrying certain KIR3DL1 alleles with HLA-B*57 is associated with protection
      from HIV infection].

PMID- 19116112
TI  - [Early embryogenesis in mammals: stem cells and first commitment steps].
AB  - In mammals, embryonic and extraembryonic cell lineages segregate during the first
      steps of cell differentiation in the preimplantation embryo. Indeed, mammal
      embryos contain very low energy stocks and thus get ready for implantation very
      early to be able to absorb nutrients from the mother, first through the yolk sac
      and then through the placenta. These first steps involve classical genetic and
      morphogenetic processes as well as specific mechanisms of early embryo
      development such as epigenetic reprogramming and maintenance of pluripotent
      cells. Embryo analysis led to the isolation of embryonic stem (ES) cells, granted
      by the 2007 Nobel prize of Medicine (to M. Evans, M. Capecchi and O. Smithies)
      and which offer strong hopes for cell therapy.

PMID- 19116113
TI  - [Oncogenic and tumour suppressor microRNAs].
AB  - microRNAs constitute one of the most important discovery in the past few years in
      the field of gene expression regulation. They can precisely regulate the
      expression of a specific protein by inhibiting its translation and/or promoting
      the degradation of its mRNA. In several cancers, the expression of some microRNAs
      is misregulated, pointing toward the existence of microRNAs with oncogenic or
      tumour suppressor properties. The miR-17-92 miRNA cluster has been reported to
      have a pro-oncogenic role in a mouse model system of Myc-induced B cell lymphoma.
      Some of its targets mRNAs code for proteins with pro-apoptotic or anti
      proliferative functions, which shed some light on the mechanism of action of this
      cluster. On the other hand, a tumour suppressor miRNA like let-7 targets mRNAs
      coding for oncogenes and is frequently down-regulated in cancers. The finding
      that c-Myc controls the expression of several of these microRNAs reveals new
      information on how misregulation of this proto-oncogene can promote
      tumorigenesis.

PMID- 19116114
TI  - [Mesenteric lymph nodes, a sanctuary for the persistance of HIV. Escape
      mechanisms].
AB  - The identification of human immunodeficiency virus type 1 (HIV-1) reservoir has
      been the center of extensive research for 25 years. In a recent work published in
      Cell Death and Differentiation, we show that mesenteric lymph nodes which drain
      intestine could represent the main reservoir for the virus. This concept has been
      established in a rhesus macaque model. Moreover, among the mechanisms associated
      with the lack of viral control, we suggest a major role of apoptosis in the death
      of CD8 T cells. This programmed cell death is associated with increased
      expression of immunosuppressive factors in lymph nodes such as TGF-b and two
      molecules regulating lymphocyte metabolism, IDO and PD-1. In this context, the
      virus benefits from the immune suppression which prevails within this
      "sanctuary", which offers optimal conditions for its persistence.

PMID- 19116115
TI  - [Hemispheric specialisation of language and brain rhythms].
AB  - How human language has evolved remains enigmatic. It is plausible to assume that
      mutual constraints of speech perception and production mechanisms shaped spoken
      communication. Speaking and understanding (speech) depend on performance limits
      of the related sensory and motor systems. Hence, the auditory apparatus evolved
      to understand speech as it is produced by the motor system, and the motor system
      such as to produce a signal that is decodable by the auditory system. Two
      theories attempt to bridge the functional properties of perceptual and motor
      language systems to account for the physical characteristics of the speech
      signal.

PMID- 19116116
TI  - [Ikaros and erythropoiesis].
AB  - Mostly studied in murine models, Ikaros--a factor that positively or negatively
      controls gene transcription--was first described as essential to lymphopoiesis
      until its involvement in numerous hematopoietic lineages was documented. Indeed,
      Ikaros is also active in murine erythropoiesis and more precisely during fetal to
      adult globin switching. Recently, these observations were confirmed by our team
      in a human context. We here review some of the most important characteristics of
      Ikaros, and detail more precisely how defects of Ikaros activity either by gene
      inactivation or mutation in mice, or by forced expression of dominant negative
      isoforms in human precursor cells, modify the erythroid differentiation. An
      increased cell death, together with decreased cell proliferation, decreased
      expression of erythroid-specific genes including GATA1, and a delay in fetal to
      adult globin switching were observed. At the same time, myeloid differentiation
      was slightly favoured thus suggesting that Ikaros could be involved in the
      control of the myeloid/erythroid commitment.

PMID- 19116117
TI  - [Comparison of proteomic strategies to identify antibodies resulting from the
      humoral immune response to cancer].
AB  - Discovery of new serum biomarkers exhibiting an increased sensitivity and
      specificity for cancer are of major importance for diagnosis improvement. There
      is considerable evidence for an immune response to cancer in humans, as
      demonstrated in part by the identification of autoantibodies against a number of
      tumour-associated antigens in sera from patients with different cancer types.
      Thus, identification of tumour-associated antigens and their associated
      antibodies is a promising strategy to find relevant biomarkers. Proteomic
      approaches such as SEREX and SERPA have allowed identification of great numbers
      of antigens and their cognate autoantibodies during these past few years. They
      show many advantages, and allowed identification of relevant autoantigens in
      different types of cancer. However, they are also time consuming, and lack
      sensibility and specificity. To circumvent these drawbacks, new proteomic
      techniques, based on protein or antibody arrays, allow high throughput analysis
      of multiple targets in a single experiment. Specific combinations of markers
      should thus be identified, theoretically being more efficient to detect a tumor
      compared to a single marker. In conclusion, these approaches promise great
      advances in the field of biomarkers for cancer. They also further need to be
      validated for clinical application on large populations.

PMID- 19116118
TI  - [Amyotrophic lateral sclerosis: role of energy deficiency in neuromuscular
      junction dismantlement].
AB  - Amyotrophic lateral sclerosis (ALS) is the most frequent adult onset motor neuron
      disorder. A subset of ALS cases is linked to mutations in the copper/zinc
      superoxide dismutase (sod1) gene and detailed phenotypic analysis of transgenic
      mice overexpressing mutant forms of SOD1 (mSOD1) allowed a better understanding
      of the pathophysiological mechanisms leading to motor neuron death. The promising
      results obtained in these animal models however poorly translated into conclusive
      clinical trials. In this review, we summarize the main pathological mechanisms at
      work in mSOD1 mice. In particular, recent results showed that the key
      pathological event was the destruction of the neuromuscular junction rather than
      motor neuron death. Neuromuscular junction dismantlement is likely the result of
      a chronic energy deficiency at the level of the whole organism. These results,
      along with a comparative analysis between the phenotype of mSOD1 mice and ALS
      patients, suggest new therapeutic strategies and show the interests but also the
      limits of the animal models.

PMID- 19116119
TI  - [The alternative NF-kB activation pathway and cancer: friend or foe?].
AB  - The family of NF-kappaB transcription factors plays a key role in diverse
      biological processes, such as inflammatory and immune responses, cell survival
      and tumor development. A new NF-kappaB activation pathway has been recently
      uncovered, the so-called alternative NF-kappaB activation pathway. It has been
      shown that this pathway mainly controls the activity of RelB, a member of the NF
      kappaB family, and its activation requires IKKalpha, one of the two catalytic
      subunits of the IKK complex. Recent studies suggest that constitutive activation
      of the alternative pathway may be involved in tumor development, but most
      surprisingly it is also reported that IKKalpha exerts a protective function
      against uncontrolled cell proliferation and cancer development. This review
      discusses recent progresses in the understanding on how the alternative pathway
      may participate in cancer development, focusing more specifically on RelB and
      IKKalpha.

PMID- 19116120
TI  - [Conflict and emerging infectious diseases].

PMID- 19116121
TI  - [Oxygen tension and cancer-cell culture: half a century of artifacts?].

PMID- 19116122
TI  - [Adiposity and cardiovascular disease: what is the best indicator of "at risk"
      obesity?].

PMID- 19116123
TI  - [The long-term preservation of scientific and technical information. PAC, the
      archive platform for digital documents at the Centre Informatique National de
      l'Enseignement Superieur].
AB  - During a fifteen years period, the long-term preservation of digital information
      has only been a matter under consideration for a few scientific or patrimonial
      institutions. These have played a key role in the understanding of the subsequent
      risks and the definition of standards in this domain. The exponential progress of
      the digital information in every domain, as well as the mandatory aspect of its
      preservation have sped up the awareness process even at the highest management
      level of companies or public administrations. Thus, a significant number of
      projects have kicked off during the last four years, with the objective of
      rolling out infrastructures dedicated to the long term preservation of electronic
      data. Among those projects, the one currently run at the CINES, which main goal
      is to provide the scientific and technical community in the Higher Education and
      Research sectors with a genuine long term preservation service for digital
      information, is now operational. Here is a brief outline of the PAC system...

PMID- 19116124
TI  - [Victor A. McKusick (1921-2008): initiator and orchestrator of the transition
      between medical genetics and genetic medicine].

PMID- 19116130
TI  - [Gp130-activating mutations in inflammatory liver adenomas].

PMID- 19116131
TI  - Isoflurane and desflurane at clinically relevant concentrations induce amyloid
      beta-peptide oligomerization: an NMR study.
AB  - Current understanding on Alzheimer's disease (AD) reveals that soluble amyloid
      beta-peptide (Abeta) oligomeric formation plays an important role in AD
      pathophysiology. A potential role for several inhaled anesthetics in promoting
      Abeta oligomer formation has been suggested. Using a nuclear magnetic resonance
      (NMR) study, we previously demonstrated that at a high concentration (higher than
      clinically relevant concentrations), the inhaled anesthetics halothane and
      isoflurane, interact with specific amino acid residues (G29, A30, and I31) and
      induce Abeta oligomerization. The present study confirms this is true at a
      clinically relevant concentration. Isoflurane and desflurane induce Abeta
      oligomerization by inducing chemical shift changes of the critical amino acid
      residues (G29, A30, and I31), reinforcing the evidence that perturbation of these
      three crucial residues indeed plays an important role in oligomerization. These
      findings support the emerging hypothesis that several commonly used inhaled
      anesthetics could be involved in neurodegeneration, as well as risk factor for
      accelerating the onset of AD.

PMID- 19116132
TI  - Obesity causes a shift in metabolic flow of gangliosides in adipose tissues.
AB  - Obesity is associated with insulin resistance and a mild chronic inflammation in
      adipose tissues. Recent studies suggested that GM3 ganglioside mediates
      dysfunction in insulin signaling. However, it has not been determined the
      ganglioside profiling in adipose tissues of obese animals. Here, we for the first
      time examined semi-quantitative ganglioside profiles in the adipose tissues of
      high fat- and high sucrose-induced obese, diabetic C57BL/6J mice by TLC and
      HPLC/mass spectrometry. In control adipose tissues GM3 dominated with traces of
      GM1 and GD1a; obesity led to a dramatic increase in GM2, GM1, and GD1a with the
      GM3 content unchanged. Similar results were obtained in KK and KKAy mice.
      Adipocytes separated from stromal vascular cells including macrophages contained
      more of those gangliosides in KKAy mice than in KK mice. These results underscore
      those gangliosides in the pathophysiology of obesity-related diseases.

PMID- 19116133
TI  - Rice OsSIPK and its orthologs: a "central master switch" for stress responses.
AB  - Mitogen-activated protein kinase (MAPK) plays a central role in controlling a
      vast array of plant biochemical and physiological processes. It is regulated by a
      characteristic phosphorelay system in which a series of three kinases
      phosphorylate and activate each other. Over the past years, several plants MAPKs
      have been identified and characterized. Of these, rice OsSIPK (Salicylic acid
      (SA)-Induced Protein Kinase) and its orthologs in other plants are of particular
      interest. A large body of evidence demonstrates the involvement of SIPKs in fine
      tuned regulation of the plant responses to ozone, wounding, SA, and jasmonic acid
      (JA). Interestingly, their function appears to be conserved across reference
      plants, such as rice, tobacco, and Arabidopsis. In this minireview, we discuss
      the recent progress on rice OsSIPK and its orthologs as a "central master switch"
      for mediating plant responses against ozone, wounding, and JA as examples.

PMID- 19116134
TI  - Suppression of endothelial t-PA expression by prolonged high laminar shear
      stress.
AB  - Primary hypertension is associated with an impaired capacity for acute release of
      endothelial tissue-type plasminogen activator (t-PA), which is an important local
      protective response to prevent thrombus extension. As hypertensive vascular
      remodeling potentially results in increased vascular wall shear stress, we
      investigated the impact of shear on regulation of t-PA. Cultured human
      endothelial cells were exposed to low (< or =1.5 dyn/cm(2)) or high (25
      dyn/cm(2)) laminar shear stress for up to 48 h in two different experimental
      models. Using real-time RT-PCR and ELISA, shear stress was observed to time and
      magnitude-dependently suppress t-PA transcript and protein secretion to
      approximately 30% of basal levels. Mechanistic experiments revealed reduced
      nuclear protein binding to the t-PA specific CRE element (EMSA) and an almost
      completely abrogated shear response with pharmacologic JNK inhibition. We
      conclude that prolonged high laminar shear stress suppresses endothelial t-PA
      expression and may therefore contribute to the enhanced risk of arterial
      thrombosis in hypertensive disease.

PMID- 19116135
TI  - Temozolomide and carmustine cause large-scale heterochromatin reorganization in
      glioma cells.
AB  - Temozolomide (TMZ) and carmustine (BCNU), cancer-drugs usually used in the
      treatment of gliomas, are DNA-methylating agents producing O6-methylguanine. It
      has been shown that 06-methylguanine triggers DNA mismatch repair and in turn
      induce apoptosis and senescence, respectively, over a 4 and 6 days period [Y.
      Hirose, M.S. Berger, R.O. Pieper, p53 effects both the duration of G2/M arrest
      and the fate of temozolomide-treated human glioblastoma cells, Cancer Res. 61
      (2001) 1957-1963; W. Roos, M. Baumgartner, B. Kaina, Apoptosis triggered by DNA
      damage O6-methylguanine in human lymphocytes requires DNA replication and is
      mediated by p53 and Fas/CD95/Apo-1, Oncogene 23 (2004) 359-367]. Here we show
      that TMZ and BCNU have an earlier effect on nuclear organization and chromatin
      structure. In particular, we report that TMZ and BCNU induce clustering of
      pericentromeric heterochromatin regions and increase the amount of
      heterochromatic proteins MeCP2 and HP1alpha bound to chromatin. These drugs also
      decrease global levels of histone H3 acetylation and increase levels of histone
      H3 trimethylated on lysine 9 (H3-triMeK9). These events precede the senescence
      status. We conclude that TMZ and BCNU efficacy in glioma treatment may implicate
      a first event characterized by changes in heterochromatin organization and its
      silencing which is then followed by apoptosis and senescence.

PMID- 19116136
TI  - Transcription factor 8 activates R-Ras to regulate angiogenesis.
AB  - We have recently reported that transcription factor 8 (TCF8) negatively regulates
      pathological angiogenesis by regulating endothelial invasiveness by acting as a
      transcriptional attenuator of matrix metalloproteinase 1. TCF8 also modulates
      cell-matrix and cell-cell adhesion; however molecular mechanism of this TCF8
      function remains obscure. Here, we provide evidence that TCF8 activates R-Ras,
      another class of angiogenic regulator, to suppress angiogenesis by a mechanism
      other than a transcriptional attenuator. Tube formation by human umbilical vein
      endothelial cells (HUVECs) facilitated by TCF8 suppression was significantly
      inhibited by the expression of constitutive active mutant of R-Ras. When we
      examined the mRNA expression levels of R-Ras regulators, no significant changes
      were observed to explain the R-Ras activation by TCF8. Interestingly, we found
      that TCF8 bound to CalDAG-GEFIII, an R-Ras activator, in the cytosol, indicating
      that TCF8 emanates signaling for R-Ras activation from cytosol to regulate
      angiogenesis negatively.

PMID- 19116137
TI  - In vitro cytotoxicity of a novel injectable and biodegradable alveolar bone
      substitute.
AB  - The unsaturated polyphosphoester (UPPE) polymer is being investigated as an
      injectable and biodegradable system for alveolar bone repair in the treatment of
      periodontal diseases. The incorporation of beta-tricalcium phosphate (beta-TCP)
      particles into the UPPE polymer was previously shown to significantly increase
      the material's mechanical properties. Moreover, in vitro experiments demonstrated
      that the UPPE/beta-TCP composite was capable of zero-order release of
      tetracycline for over 2 weeks. In this study, we investigated the in vitro
      cytotoxicity of each individual component, the resulting cross-linked network and
      the degradation products of the UPPE/beta-TCP composite using an AlamarBlue
      viability assay. We confirmed that each individual component except beta-TCP and
      the in vitro degradation products of the composite displayed a dose-dependent
      cytotoxic response. Once cross-linked, however, the composite did not demonstrate
      an adverse response. Our results suggest that the UPPE/beta-TCP composite holds
      great promise for use as an injectable and biodegradable alveolar bone
      substitute.

PMID- 19116138
TI  - Role for the first SH3 domain of p67phox in activation of superoxide-producing
      NADPH oxidases.
AB  - The membrane-bound NADPH oxidase in phagocytes, gp91(phox) (a.k.a. Nox2),
      produces superoxide, a precursor of microbicidal oxidants, thereby playing a
      crucial role in host defense. Activation of gp91(phox)/Nox2 requires assembly
      with the cytosolic proteins p67(phox) and p47(phox), each containing two SH3
      domains. Although the C-terminal SH3 domain of p67(phox) is responsible for
      binding to p47(phox), little is known about the role for the first (N-terminal)
      SH3 domain [SH3(N)]. Here we show that truncation of p67(phox)-SH3(N), but not
      substitution of arginine for the invariant residue Trp-277 in SH3(N), results in
      an impaired activation of gp91(phox)/Nox2. The impairment is overcome by higher
      expression of an SH3(N)-defective p67(phox) in cells, suggesting that SH3(N)
      primarily increases the affinity of p67(phox) for the oxidase complex. On the
      other hand, p67(phox)-SH3(N) is not involved in activation of Nox1 and Nox3,
      closely-related homologues of gp91(phox)/Nox2. Thus p67(phox)-SH3(N) specifically
      functions in gp91(phox)/Nox2 activation probably via facilitating oxidase
      assembly.

PMID- 19116139
TI  - Capsaicin binds to prohibitin 2 and displaces it from the mitochondria to the
      nucleus.
AB  - Capsaicin is widely used as a food additive and as an analgesic agent. Besides
      its well-known role in nociception, which is mediated by vanilloid receptor 1
      specifically expressed in dorsal root ganglion neurons, capsaicin has also been
      considered as a potential anticancer agent, as it inhibits cell proliferation and
      induces apoptosis in various types of cancer cells. Here we identified a new
      molecular target of capsaicin from human myeloid leukemia cells. We show that
      capsaicin binds to prohibitin (PHB) 2, which is normally localized to the inner
      mitochondrial membrane, and induces its translocation to the nucleus. PHB2 is
      implicated in the maintenance of mitochondrial morphology and the control of
      apoptosis. We also provide evidence suggesting that capsaicin causes apoptosis
      directly through the mitochondria and that PHB2 contributes to capsaicin-induced
      apoptosis at multiple levels. This work will serve as an important foundation for
      further understanding of anticancer activity of capsaicin.

PMID- 19116140
TI  - EGF promotes invasion by PANC-1 cells through Rac1/ROS-dependent secretion and
      activation of MMP-2.
AB  - Cancer metastasis involves tumor cells invading the surrounding tissue.
      Remodeling of tissue barriers depends on the ability of tumor cells to degrade
      the surrounding collagen matrix and then migrate through the matrix defects.
      Epidermal growth factor (EGF) has been shown to regulate tumor cell invasion
      through activation of matrix metalloproteinase-2 (MMP-2) in various tumor cell
      types. In the present study, we investigated the role of MMP-2 and the signaling
      pathway involved in EGF-promoted invasion by human pancreatic cancer cells PANC
      1. Using specific inhibitors, we found that EGF stimulation of these tumor cells
      induced secretion and activation of the collagenase MMP-2, which was required for
      EGF-stimulated basement membrane degradation and cell invasion. Our results also
      indicate that signaling events downstream of EGF receptor involved PI3K- and Src
      dependent activation of Rac1, which mediated the NADPH-generated reactive oxygen
      species responsible for MMP-2 secretion and activation.

PMID- 19116142
TI  - Cooperativity of two active sites in bacterial homodimeric aconitases.
AB  - Aconitase catalyzes a reversible isomerization of citrate into isocitrate in the
      Krebs cycle. Escherichia coli possesses two kinds of aconitases, aconitase A
      (AcnA) and B (AcnB), whose structural organizations are different. We analyzed
      the structural state of AcnA by the chemical crosslinking and small-angle X-ray
      scattering. The protein adopts a homodimer in solution, as AcnB does. The
      catalytic assay of the two aconitases revealed that the isomerization of
      isocitrate displayed a negative cooperativity of the two active sites within each
      homodimer. On the other hand, insignificant cooperativity was observed in the
      reverse reaction. Therefore, the homodimerization of AcnAB yields a substrate
      dependent cooperative effect. In conjunction with the dissociable homodimer of
      AcnB, the catalytic property could affect the intracellular metabolic process
      involving the Krebs cycle.

PMID- 19116141
TI  - Chimeric mice reveal clonal development of pancreatic acini, but not islets.
AB  - Intestinal crypt stem cells establish clonal descendants. To determine whether
      the pancreas is patterned by a similar process, we used embryonic stem (ES) cell
      chimeric mice, in which male ES cells were injected into female blastocysts.
      Fluorescence in situ hybridization for the Y chromosome (Y-FISH) revealed clonal
      patterning of ES-derived cells in the adult mouse small intestine and pancreas.
      Intestinal crypts were entirely male or entirely female. Villi contained columns
      of male or female epithelial cells, consistent with upward migration of cells
      from the crypts which surround them. Within the exocrine pancreas, acini were
      entirely male or entirely female, consistent with patterning from a single
      stem/progenitor cell. Pancreatic islets contained a mixture of male and female
      cells, consistent with patterning from multiple progenitors. Male-female chimeric
      mice demonstrate that the adult mouse exocrine pancreatic acinus is patterned
      from a single stem/progenitor cell, while the endocrine pancreas arises from
      multiple progenitors.

PMID- 19116143
TI  - Structural and functional analysis of a novel EstE5 belonging to the subfamily of
      hormone-sensitive lipase.
AB  - Hormone-sensitive lipase (HSL) plays an important role in the regulation of
      rodent fat cell lipolysis. It is regarded as an adipose tissue-specific enzyme
      whose sole metabolic role is the catalysis of hormone-stimulated lipolysis in
      mammalian cells. In this report we describe the functional and structural
      analysis of an EstE5 protein from a soil metagenome library. Function analysis
      results indicated that EstE5 preferentially hydrolyzes short-chain ester
      compounds, and our kinetic studies revealed the optimal pH and temperature. Based
      on the structural analysis, we defined the active site and the binding pocket.
      Structurally, EstE5 belongs to the HSL family and these structural studies may
      have applications in the production of value-added products, including
      pharmaceuticals.

PMID- 19116144
TI  - Positive modulation of RNA polymerase III transcription by ribosomal proteins.
AB  - A yeast nuclear fraction of unknown composition, named TFIIIE, was reported
      previously to enhance transcription of tRNA and 5S rRNA genes in vitro. We show
      that TFIIIE activity co-purifies with a specific subset of ribosomal proteins
      (RPs) which, as revealed by chromatin immunoprecipitation analysis, generally
      interact with tRNA and 5S rRNA genes, but not with a Pol II-specific promoter.
      Only Rpl6Ap and Rpl6Bp, among the tested RPs, were found associated to a TATA
      containing tRNA(Ile)(TAT) gene. The RPL6A gene also emerged as a strong multicopy
      suppressor of a conditional mutation in the basal transcription factor TFIIIC,
      while RPL26A and RPL14A behaved as weak suppressors. The data delineate a novel
      extra-ribosomal role for one or a few RPs which, by influencing 5S rRNA and tRNA
      synthesis, could play a key role in the coordinate regulation of the different
      sub-pathways required for ribosome biogenesis and functionality.

PMID- 19116145
TI  - Epigenetic therapy upregulates the tumor suppressor microRNA-126 and its host
      gene EGFL7 in human cancer cells.
AB  - Studies have shown that aberrant expression of miRNAs is involved in the
      initiation and progression of cancer, and several miRNAs have been characterized
      as tumor suppressors or oncogenes. Restoring the expression of tumor suppressor
      genes by epigenetic therapy has great potential in cancer treatment and it has
      been shown that some miRNAs can be directly regulated from their own promoters by
      epigenetic alterations in cancer cells. However, the majority of miRNAs are
      located within intronic regions of transcription units and it was unclear if
      intronic miRNAs can also be epigenetically regulated. Here we show that the tumor
      suppressor miR-126, which is located within an intron of the EGFL7 gene, is
      downregulated in cancer cell lines and in primary bladder and prostate tumors.
      Mature miR-126 can be generated from three different transcripts of EGFL7 with
      each one having its own promoter. Interestingly, miR-126 and one of the
      transcripts of EGFL7 that has a CpG island promoter are concomitantly upregulated
      in cancer cell lines by inhibitors of DNA methylation and histone deacetylation.
      These findings suggest that epigenetic changes can control the expression of
      tumor suppressor intronic miRNAs by directly controlling their host genes. Thus,
      epigenetic therapy not only directly activates miRNAs from their own promoters,
      but also activates intronic miRNAs together with their host genes. This reveals
      an additional mechanism and anticancer effect of epigenetic therapy.

PMID- 19116147
TI  - Zeb1-mediated T-cadherin repression increases the invasive potential of
      gallbladder cancer.
AB  - Here, we report that the transcriptional regulator Zeb1 repressed the
      transcription of T-cadherin, to increase the invasive activity of gallbladder
      cancer cells. Zeb1 physically bound to the promoter of T-cadherin, repressed
      promoter activity in E-box-like sequence-dependent fashion, and suppressed T
      cadherin expression. In gallbladder cancer tissues, Zeb1 was expressed at the
      cancer invasion front, whereas T-cadherin was exclusively expressed in non
      invasive foci. Collagen gel invasion assay showed that T-cadherin was a negative
      regulator for gallbladder cancer invasion. These findings suggest that Zeb1
      represses T-cadherin expression and thus increases the invasive activity of
      gallbladder cancer.

PMID- 19116146
TI  - sPLA2-IIa is an inflammatory mediator when the ocular surface is compromised.
AB  - sPLA2-IIa is an enzyme at high concentration in tears that has been known as an
      innate barrier of the ocular surface against microbial infection. sPLA2-IIa and
      other enzymes in the same protein family are known to hydrolyze fatty acids
      resulting in the generation of free arachidonic acid (AA) and lysophospholipids,
      which are the precursors of pro-inflammatory lipid mediators, such as PGE(2).
      sPLA2-IIa has been shown to be an inflammatory mediator in non-ocular
      inflammatory diseases such as rheumatoid arthritis (RA). It was also found to be
      increased in the tears of the patients with dry eye disease, chronic blepharitis
      and contact lens intolerance. However, the role of sPLA2-IIa in chronic ocular
      surface inflammation has yet to be determined. In the current study, we examined
      the potential role of sPLA2-IIa in inflammation of ocular surface diseases. Our
      results show that the activity of sPLA2-IIa was significantly increased in tears
      from dry eye disease patients compared with that from normal subjects. Also,
      sPLA2-IIa stimulated the production of PGE(2) in ocular surface epithelial cell
      cultures. The stimulating effect was markedly enhanced when the cells or tissues
      were pre-compromised with TNF-alpha, IL-1beta or desiccation. Furthermore, sPLA2
      IIa stimulated inflammatory cytokine production in the ocular surface epithelial
      cell cultures in vitro. To our knowledge, this is the first report regarding the
      role of sPLA2-IIa as an inflammatory mediator in ocular surface inflammation.
      These findings indicate that sPLA2-IIa may play an important role in chronic
      ocular surface inflammation, especially when the ocular surface is compromised.

PMID- 19116148
TI  - Identification of a novel point mutation in ENT1 that confers resistance to Ara-C
      in human T cell leukemia CCRF-CEM cells.
AB  - The genetic basis for the Ara-C resistance of CCRF-CEM Ara-C/8C leukemia cells
      was investigated. DNA sequencing revealed that these cells expressed an
      equilibrative nucleoside transporter 1 (ENT1) with a single missense mutation
      resulting in glycine to arginine replacement (G24R). To test the importance of
      this residue, additional G24 mutants were created and examined for [3H]-uridine
      and [3H]-Ara-C uptake. Both a G24E and G24A mutant showed reduced ENT1-dependent
      activity. An EGFP-tagged G24R ENT1 displayed plasma membrane localization even
      though it was unable to bind [3H]-NBMPR, an ENT1-specific inhibitor. These
      results define G24 as critical amino acid for ENT1 nucleoside uptake and suggest
      that mutations in TM1 may provide a mechanism for Ara-C resistance in CCRF-CEM
      Ara-C/8C cells.

PMID- 19116149
TI  - Targeting STAT1 by myricetin and delphinidin provides efficient protection of the
      heart from ischemia/reperfusion-induced injury.
AB  - Flavonoids exhibit a variety of beneficial effects in cardiovascular diseases.
      Although their therapeutic properties have been attributed mainly to their
      antioxidant action, they have additional protective mechanisms such as inhibition
      of signal transducer and activator of transcription 1 (STAT1) activation. Here,
      we have investigated the cardioprotective mechanisms of strong antioxidant
      flavonoids such as quercetin, myricetin and delphinidin. Although all of them
      protect the heart from ischemia/reperfusion-injury, myricetin and delphinidin
      exert a more pronounced protective action than quercetin by their capacity to
      inhibit STAT1 activation. Biochemical and computer modeling analysis indicated
      the direct interaction between STAT1 and flavonoids with anti-STAT1 activity.

PMID- 19116150
TI  - CAP (Cbl associated protein) regulates receptor-mediated endocytosis.
AB  - CAP (c-Cbl associated protein)/ponsin belongs to a family of adaptor proteins
      implicated in cell adhesion and signaling. Here we show that CAP binds to and co
      localizes with the essential endocytic factor dynamin. We demonstrate that CAP
      promotes the formation of dynamin-decorated tubule like structures, which are
      also coated with actin filaments. Accordingly, we found that the expression of
      CAP leads to the inhibition of dynamin-mediated endocytosis and increases EGFR
      stability. Thus, we suggest that CAP may coordinate the function of dynamin with
      the regulation of the actin cytoskeleton during endocytosis.

PMID- 19116151
TI  - Characterization of the Caenorhabditis elegans Islet LIM-homeodomain ortholog,
      lim-7.
AB  - lim-7 is one of seven Caenorhabditis elegans LIM-homeodomain (LIM-HD)-encoding
      genes and the sole Islet ortholog. LIM-HD transcription factors, including
      Islets, function in neuronal and non-neuronal development across diverse phyla.
      Our results show that a lim-7 deletion allele causes early larval lethality with
      terminal phenotypes including uncoordination, detached pharynx, constipation and
      morphological defects. A lim-7(+) transgene rescues lethality but not adult
      sterility. A lim-7(+) reporter in the full genomic context is expressed in all
      gonadal sheath cells, URA neurons, and additional cells in the pharyngeal region.
      Finally, we identify a 45-bp regulatory element in the first intron that is
      necessary and sufficient for lim-7 gonadal sheath expression.

PMID- 19116152
TI  - Cu,Zn-superoxide dismutase is necessary for proper function of VDAC in
      Saccharomyces cerevisiae cells.
AB  - Available data suggest that a copper-and zinc-containing dismutase (CuZnSOD)
      plays a significant role in protecting eukaryotic cells against oxidative
      modifications which may contribute to cell aging. Here we demonstrated that
      depletion of CuZnSOD in Saccharomyces cerevisiae cells (Deltasod1 cells) affected
      distinctly channel activity of VDAC (voltage dependent anion selective channel)
      and resulted in a moderate reduction in VDAC levels as well as in levels of
      protein crucial for VDAC import into mitochondria, namely Tob55/Sam50 and Tom40.
      The observed alterations may result in mitochondriopathy and subsequently in the
      shortening of the replicative life span observed for S. cerevisiaeDeltasod1
      cells.

PMID- 19116153
TI  - Regulation of focal adhesion formation and filopodia extension by the cellular
      prion protein (PrPC).
AB  - While the prion protein (PrP) is clearly involved in neuropathology, its
      physiological roles remain elusive. Here, we demonstrate PrP functions in cell
      substrate interaction in Drosophila S2, N2a and HeLa cells. PrP promotes cell
      spreading and/or filopodia formation when overexpressed, and lamellipodia when
      downregulated. Moreover, PrP normally accumulates in focal adhesions (FAs), and
      its downregulation leads to reduced FA numbers, increased FA length, along with
      Src and focal adhesion kinase (FAK) activation. Furthermore, its overexpression
      elicits the formation of novel FA-like structures, which require intact
      reggie/flotillin microdomains. Altogether, PrP modulates process formation and FA
      dynamics, possibly via signal transduction involving FAK and Src.

PMID- 19116154
TI  - Salinity effects on the expression of osmoregulatory genes in the euryhaline
      black porgy Acanthopagrus schlegeli.
AB  - Black porgy is a marine euryhaline species with a capacity to cope with demands
      in a wide range of salinities and thus is a perfect model-fish to study
      osmoregulatory responses to salinity-acclimated processes and their hormonal
      control. The present study was performed to understand the regulatory changes in
      hormone, hormone receptors and important osmoregulatory genes in pituitary, gill,
      intestine and kidney in response to acute salinity stress. Transcript levels were
      analyzed by quantitative real-time PCR following acute salinity challenge by
      direct transfer of seawater (SW) acclimatized fish to fresh water (FWBP) and vice
      versa (SWBP). SW acclimation significantly increased plasma osmolality and
      intestine Na+/K+-ATPase (NKA) activity while FW acclimation increased plasma
      cortisol and branchial NKA activity. Plasma osmolality and chloride concentration
      decreased in FWBP whereas GH levels remained unchanged in both FWBP and SWBP.
      Comparative analysis of gene profiles between FWBP and SWBP showed that pituitary
      prolactin transcript increased significantly in FWBP. Prolactin receptor (PRLR)
      transcripts increased in gill of FWBP while it decreased in gill and kidney of
      SWBP. NKA transcripts increased in gill of both FWBP and SWBP, while it decreased
      in intestine of FWBP and increased in intestine and kidney of SWBP.
      Glucocorticoid receptor (GR) transcripts decreased in intestine and kidney of
      FWBP while it increased in gill and intestine of SWBP. No significant changes
      were observed in growth hormone receptor (GHR) transcripts of both FWBP and SWBP
      in pituitary, gill, intestine and kidney. Our current data demonstrated the
      correlation between PRLR gene expression in relation to FW adaptation, and GR
      gene expression in relation to SW adaptation in euryhaline black porgy. The
      results indicate that black porgy has an excellent osmoregulatory capacity and is
      capable of withstanding large variations in salinity.

PMID- 19116155
TI  - Corticosterone and corticosteroid binding globulin in birds: relation to
      urbanization in a desert city.
AB  - As cities expand worldwide, understanding how species adapt to novel urban
      habitats will become increasingly important to conservation. The adrenocortical
      stress response enables vertebrates to cope with novel environmental challenges
      to homeostasis. We examined total and estimates of free baseline and stress
      induced corticosterone (CORT) concentrations and CORT binding globulin (CBG)
      levels in five passerine species within and around Phoenix, Arizona. We tested
      whether baseline and stress-induced CORT patterns differed among species living
      at varying densities in Phoenix and tested the hypothesis that, for species
      capable of successfully colonizing cities, individuals living in urban areas have
      a decreased acute stress response compared to individuals living in native
      desert. Baseline total CORT levels were generally similar in urban and rural
      birds. Capture and handling stress typically produced greater total CORT
      responses in urban birds than in rural birds, although these responses differed
      as a function of the life history stage (non-breeding, breeding or molt). CBG
      binding capacity did not change with life history stage or locality. Estimated
      free CORT concentrations differed less between groups than total CORT
      concentrations. Urban birds showed less variability in stress responses across
      life history stages than rural birds. We propose that more predictable resources
      in the city than in rural areas may decrease the need to vary stress
      responsiveness across life history stages. The results highlight the species
      specific effects of urbanization on stress physiology and the difficulty to
      predict how urbanization impacts organisms.

PMID- 19116156
TI  - A temporal shift in regulatory networks and pathways in the bovine small
      intestine during Cooperia oncophora infection.
AB  - Cooperia oncophora is an important parasitic nematode of cattle with a wide
      distribution in temperate areas. Twenty Holstein nematode-naive bull calves were
      experimentally infected with approximately 100,000 infective L3s and infection
      was allowed to progress for 7, 14, 28, 42 days, respectively. This experiment was
      conducted to identify putative recognition and inflammatory pathways in the host
      parasite relationship. Gene expression profiles of the small intestine were
      compared using a high-density bovine 60 mer oligo microarray. A total of 310
      genes were differentially expressed during the course of infection. The pathways
      and regulatory networks significantly impacted by the infection were analysed. A
      total of 22 canonical pathways and nine regulatory networks were significantly
      affected during infection. During the early phase of the infection (7 days p.i.),
      parasites suppressed the acute phase response and the complement system of the
      host. At 14 days p.i., three out of the six pathways impacted were related with
      retinoid X receptor (RXR) functions. At 28 days p.i., the effects on RXR were
      less evident. The host response shifted to lipid metabolism and signalling,
      especially eicosanoid production and signalling, suggesting that eicosanoid
      mediated inflammation might be a major host defence mechanism. By 42 days p.i.,
      the pathways impacted involved glycosphingolipid biosynthesis and transforming
      growth factor beta (TGFbeta signalling. The expression of cadherin-like 26
      (CDH26) was strongly up-regulated starting at 14 days p.i. and peaked at 28 days
      p.i. The extent of its expression is positively correlated with the infiltration
      of eosinophils (R=0.82) and coincides with the number of adult parasites in the
      tissue. CDH26 demonstrated an expression profile similar to two other cell
      adhesion molecules involved in recognition of carbohydrates on foreign organisms,
      collectin and galectin, suggesting that it may serve as a pattern recognition
      molecule for C. oncophora. These results provide a potential molecular roadmap
      for future studies aimed at defining host immune responses and understanding
      protective immunity against gastrointestinal nematodes.

PMID- 19116157
TI  - Spatio-temporal patterns of gene flow and dispersal under temperature increase.
AB  - Recent data show that the Earth climate is undergoing a change at a rate which is
      outstanding in geologic history. Temperature is one of the major driving forces
      of gene flow and dispersal. In this paper the spatial dynamics of genetic
      dispersal is studied under the auspices of temperature increase by means of a
      mathematical model. The main elements genetics, competition and dispersal are
      combined in a coherent approach by a system of coupled partial differential
      equations with non-linear reaction terms describing population dynamics, genetic
      exchange and competition. Temperature reaction norms are conferred by a two
      allele system. The non-linearities of the interaction terms give rise to a
      richness of spatio-temporal dynamic patterns. Here we show how invasion processes
      in form of travelling waves are initiated by a temperature rise.

PMID- 19116158
TI  - The coevolution of two phytoplankton species on a single resource: allelopathy as
      a pseudo-mixotrophy.
AB  - Without the top-down effects and the external/physical forcing, a stable
      coexistence of two phytoplankton species under a single resource is impossible -
      a result well known from the principle of competitive exclusion. Here I
      demonstrate by analysis of a mathematical model that such a stable coexistence in
      a homogeneous media without any external factor would be possible, at least
      theoretically, provided (i) one of the two species is toxin producing thereby has
      an allelopathic effect on the other, and (ii) the allelopathic effect exceeds a
      critical level. The threshold level of allelopathy required for the coexistence
      has been derived analytically in terms of the parameters associated with the
      resource competition and the nutrient recycling. That the extra mortality of a
      competitor driven by allelopathy of a toxic species gives a positive feed back to
      the algal growth process through the recycling is explained. And that this
      positive feed back plays a pivotal role in reducing competition pressures and
      helping species succession in the two-species model is demonstrated. Based on
      these specific coexistence results, I introduce and explain theoretically the
      allelopathic effect of a toxic species as a 'pseudo-mixotrophy'-a mechanism of
      'if you cannot beat them or eat them, just kill them by chemical weapons'. The
      impact of this mechanism of species succession by pseudo-mixotrophy in the form
      of alleopathy is discussed in the context of current understanding on straight
      mixotrophy and resource-species relationship among phytoplankton species.

PMID- 19116159
TI  - A neutral model of edge effects.
AB  - In this paper a spatially implicit neutral model for explaining the edge effects
      between habitats is proposed. To analyze this model we use two different
      approaches: a discrete approach that is based on the Master equation for a one
      step jump process and a continuous approach based on the approximation of the
      discrete jump process with the Kolmogorov-Fokker-Planck forward and backward
      equations. The discrete and continuous approaches are applied to analyze the
      species abundance distributions and the time to species extinction. Moreover,
      with the aid of the continuous approach a realistic classification of the
      behavior of species in local communities is developed. The species abundance
      dynamics at the edge between two distinct habitats is compared with those located
      in the homogeneous interior habitats using species abundance distributions and
      the first time to species extinction. We show that the structure of the links
      between local community and the metacommunity plays an important role on species
      persistence. Specifically, species at the edge between two distinct
      metacommunities have higher extinction rate than those in the interior habitats
      connected only to one metacommunity. Moreover, the same species might be
      persistent in the homogeneous interior habitat, but its probability of extinction
      from the edge local community could be very high.

PMID- 19116160
TI  - Structuring food emulsions in the gastrointestinal tract to modify lipid
      digestion.
AB  - The importance of nutrient lipids in the human diet has led to major advances in
      understanding the mechanisms of lipid digestion and absorption. With these
      advances has come new recognition that the matrix in which lipids are presented
      (i.e. food structure) in the diet could influence the rate of lipid digestion and
      hence the bioavailability of fatty acids. As a consequence, there is growing
      interest in understanding how food material properties can be manipulated under
      physiological conditions to control the uptake of lipids and lipid-soluble
      components. The lipids in many, if not most, processed foods are normally present
      as emulsions, which can be end products in themselves or part of a more complex
      food system. In this review, we discuss the formation and properties of oil-in
      water (O/W) emulsions, especially how these emulsions are modified as they
      traverse through the gastrointestinal tract. Among other factors, the changes in
      the nature of the droplet adsorbed layer and the droplet size play a major role
      in controlling the action of lipases and lipid digestion. Greater knowledge and
      understanding of how the digestive system treats, transports and utilizes lipids
      will allow the microstructural design of foods to achieve a specific, controlled
      physiological response.

PMID- 19116161
TI  - Residues of lambda-cyhalothrin in tea.
AB  - Field experiments were conducted at two places in Tamil Nadu (India) during dry
      season of 2006 to determine the residues of lambda-cyhalothrin in fresh green tea
      leaves and black tea. Residues were quantified at different harvest intervals of
      '0' (3h), 1st, 3rd, 5th, 7th, 10th and 14th day after insecticide application.
      Persistence, dissipation pattern, half-life value and safe harvest interval of
      the insecticide in tea were calculated. Residues of lambda-cyhalothrin dissipated
      exponentially after application at both the locations and reached below the
      European Union maximum residue limit (MRL) of 1mg/kg on the 5th day. Lambda
      cyhalothrin showed that like other insecticides it followed the first order
      dissipation kinetics. Half-life values varied from 2.8 to 3.5 days for lambda
      cyhalothrin and a safety harvest interval of 5 days is suggested for tea at the
      recommended dosage.

PMID- 19116162
TI  - Microinjection of angiotensin II in the caudal ventrolateral medulla induces
      hyperalgesia.
AB  - Nociceptive transmission from the spinal cord is controlled by supraspinal pain
      modulating systems that include the caudal ventrolateral medulla (CVLM). The
      neuropeptide angiotensin II (Ang II) has multiple effects in the CNS and at the
      medulla oblongata. Here we evaluated the expression of angiotensin type 1 (AT(1))
      receptors in spinally-projecting CVLM neurons, and tested the effect of direct
      application of exogenous Ang II in the CVLM on nociceptive behaviors. Although
      AT(1)-immunoreactive neurons occurred in the CVLM, only 3% of AT(1)-positive
      neurons were found to project to the dorsal horn, using double-immunodetection of
      the retrograde tracer cholera toxin subunit B. In behavioral studies,
      administration of Ang II (100 pmol) in the CVLM gave rise to hyperalgesia in both
      the tail-flick and formalin tests. This hyperalgesia was significantly attenuated
      by local administration of the AT(1) antagonist losartan. The present study
      demonstrates that Ang II can act on AT(1) receptors in the CVLM to modulate
      nociception. The effect on spinal nociceptive processing is likely indirect,
      since few AT(1)-expressing CVLM neurons were found to project to the spinal cord.
      The renin-angiotensin system may also play a role in other supraspinal areas
      implicated in pain modulation.

PMID- 19116163
TI  - The 'microEST' in vitro test for embryotoxicity - validated and endorsed or not?

PMID- 19116165
TI  - Didymella pisi sp. nov., the teleomorph of Ascochyta pisi.
AB  - The anamorphic pycnidial fungus Ascochyta pisi is one member of a species complex
      that causes Ascochyta blight of pea, a potentially devastating disease. The
      teleomorphic state of this fungus was induced under laboratory conditions. Using
      morphological and molecular characters, we placed the teleomorph within the genus
      Didymella as D. pisi and describe a heterothallic mating system using a PCR-based
      mating type assay and in vitro crosses. We compare D. pisi with other Didymella
      spp. with which it might be confused.

PMID- 19116164
TI  - Genetic interaction between Bmp2 and Bmp4 reveals shared functions during
      multiple aspects of mouse organogenesis.
AB  - Vertebrate Bmp2 and Bmp4 diverged from a common ancestral gene and encode closely
      related proteins. Mice homozygous for null mutations in either gene show early
      embryonic lethality, thereby precluding analysis of shared functions. In the
      current studies, we present phenotypic analysis of compound mutant mice
      heterozygous for a null allele of Bmp2 in combination with null or hypomorphic
      alleles of Bmp4. Whereas mice lacking a single copy of Bmp2 or Bmp4 are viable
      and have subtle developmental defects, compound mutants show embryonic and
      postnatal lethality due to defects in multiple organ systems including the
      allantois, placental vasculature, ventral body wall, skeleton, eye and heart.
      Within the heart, BMP2 and BMP4 function coordinately to direct normal
      lengthening of the outflow tract, proper positioning of the outflow vessels, and
      septation of the atria, ventricle and atrioventricular canal. Our results
      identify numerous BMP4-dependent developmental processes that are also very
      sensitive to BMP2 dosage, thus revealing novel functions of Bmp2.

PMID- 19116166
TI  - Molecular characterization and enzymatic activity of laccases in two Pleurotus
      spp. with different pathogenic behaviour.
AB  - Pleurotus eryngii and P. ferulae, two species belonging to the P. eryngii
      complex, synthesize laccases, ligninolytic enzymes that play a role in the host
      pathogen interaction in the first step of infection. Ecological studies have
      shown that although both fungi have been recognized as saprophytes, P. eryngii
      weakly pathogenic when colonizing the roots and stems of Eryngium campestre,
      whereas P. ferulae is mostly pathogenic to Ferula communis. The paper describes
      the genomic organization of four putative laccase genes (lac1, lac2, lac3, and
      lac5-like gene; gene names were assigned on the basis of sequence homologies) of
      P. eryngii and P. ferulae. The mRNA expression and enzymatic activity of the
      laccases were analysed under culture conditions where a source of lignin (wheat
      bran) or lyophilized roots of E. campestre or F. communis were present. These
      experiments indicated that the four lac-like genes were differentially regulated
      in the two mushrooms. Specifically, the addition of the lyophilized roots of the
      respective host plant to the culture media induced an advance in the mRNA
      expression of the four lac-like genes and a seven-fold higher total laccase
      activity in P. ferulae than in P. eryngii. The results obtained are discussed in
      relation to the possible role of laccases in the interaction of P. eryngii and P.
      ferulae with their respective host.

PMID- 19116167
TI  - Purification and properties of a chitinase from Penicillium sp. LYG 0704.
AB  - The chitinase producing Penicillium sp. LYG 0704 was procured from soil of the
      Chonnam National University crop field. The chitinase activity was detected after
      the first day which increased gradually and reached its maximum after 3 days of
      cultivation. The chitinase was purified from a culture medium by precipitation
      with isopropanol and column chromatography with Mono Q and Butyl-Sepharose. The
      molecular mass of chitinase was estimated to be 47 kDa by SDS-PAGE. Optimal pH
      and temperature were 5.0 and 40 degrees C, respectively. The N-terminal amino
      acid sequence of the enzyme was determined to be (1)AGSYRSVAYFVDWAI(15). The
      fully cloned gene, 1287 bp in size, encoded a single peptide of 429 amino acids.
      BLAST search of the chitinase gene sequence showed similarity with chitinase of
      Aspergillus fumigatus Af293 chitinase gene (58%) and A. fumigatus class V
      chitinase ChiB1 gene (56%).

PMID- 19116168
TI  - Bioprocess development for production, purification, and structural
      characterization of recombinant hCD83ext as a potential therapeutic protein.
AB  - An effective bioprocess for the production of hCD83ext (i.e. the extracytoplasmic
      domain of human CD83) as a potential therapeutic protein was developed. It
      primarily consists of (1) cell cultivation for the production of recombinant
      glutathione-S-transferase-hCD83ext (GST-hCD83ext) fusion protein and (2)
      downstream processing for purification of hCD83ext. The developed bioprocess is
      robust, reproducible, easy to operate, and, most importantly, can generate
      hCD83ext with a high yield and purity. For cell cultivation, a high GST-hCD83ext
      expression level, estimated to be more than 10% of total cellular protein, with a
      cell density of 8 OD(600) was obtained by tuning several culture parameters,
      including medium recipe, host/vector system, induction condition, temperature,
      and aeration. For downstream processing, milligrams of very pure and low
      endotoxin hCD83ext was obtained through simultaneous binding and cleavage of GST
      hCD83ext in a GST affinity chromatographic column followed by a polishing step
      using anion exchange chromatography. To identify potential factors associated
      with bioactivity consistency, structural changes for the final product of
      hCD83ext were characterized and monitored. Formation of various hCD83ext
      multimeric forms, including dimer, trimer, and tetramer, via intermolecular
      disulfide bonds was observed.

PMID- 19116169
TI  - Chaperone-assisted production of active human Rab8A GTPase in Escherichia coli.
AB  - The guanine nucleotide binding protein Rab8A controls the final steps of
      exocytosis in mammalian cells. It has been implicated in the regulation of apical
      protein localization in intestinal epithelial cells and ciliary biogenesis. The
      in vitro structural and biochemical characterization of Rab8A and its interaction
      with regulator and effector molecules has been hampered by its insolubility in
      Escherichia coli expression systems. The conventional refolding procedure is
      laborious and yields only minute amounts of C-terminally truncated Rab8A (Rab8A(1
      183): amino acids 1-183), not the full-length protein. Here, we report a method
      of expressing soluble, hexahistidine-tagged full-length human Rab8A from E. coli.
      The Rab8A gene was codon-optimized and coexpressed with bacterial GroEL and GroES
      chaperones. After two-step purification by Ni(2+) affinity chromatography and gel
      filtration, Rab8A was obtained at a yield of 4 mg protein per 1L of bacterial
      cell culture and a purity of >95%. The resultant protein was functionally active,
      as determined by GTPase activity and its interaction with the nucleotide exchange
      factor MSS4.

PMID- 19116170
TI  - 3D morphology of the human hepatic ferritin mineral core: new evidence for a
      subunit structure revealed by single particle analysis of HAADF-STEM images.
AB  - Ferritin, the major iron storage protein, has dual functions; it sequesters redox
      activity of intracellular iron and facilitates iron turn-over. Here we present
      high angle annular dark field (HAADF) images from individual hepatic ferritin
      cores within tissue sections, these images were obtained using spherical
      aberration corrected scanning transmission electron microscopy (STEM) under
      controlled electron fluence. HAADF images of the cores suggest a cubic morphology
      and a polycrystalline (ferrihydrite) subunit structure that is not evident in
      equivalent bright field images. By calibrating contrast levels in the HAADF
      images using quantitative electron energy loss spectroscopy, we have estimated
      the absolute iron content in any one core, and produced a three dimensional
      reconstruction of the average core morphology. The core is composed of up to
      eight subunits, consistent with the eight channels in the protein shell that
      deliver iron to the central cavity. We find no evidence of a crystallographic
      orientation relationship between core subunits. Our results confirm that the
      ferritin protein shell acts as a template for core morphology and within the
      core, small (approximately 2 nm), surface-disordered ferrihydrite subunits
      connect to leave a low density centre and a high surface area that would allow
      rapid turn-over of iron in biological systems.

PMID- 19116171
TI  - 3D imaging of mammalian cells with ion-abrasion scanning electron microscopy.
AB  - Understanding the hierarchical organization of molecules and organelles within
      the interior of large eukaryotic cells is a challenge of fundamental interest in
      cell biology. We are using ion-abrasion scanning electron microscopy (IA-SEM) to
      visualize this hierarchical organization in an approach that combines focused ion
      beam milling with scanning electron microscopy. Here, we extend our previous
      studies on imaging yeast cells to image subcellular architecture in human
      melanoma cells and melanocytes at resolutions as high as approximately 6 and
      approximately 20 nm in the directions parallel and perpendicular, respectively,
      to the direction of ion-beam milling. The 3D images demonstrate the striking
      spatial relationships between specific organelles such as mitochondria and
      membranes of the endoplasmic reticulum, and the distribution of unique cellular
      components such as melanosomes. We also show that 10nm-sized gold particles and
      quantum dot particles with 7 nm-sized cores can be detected in single cross
      sectional images. IA-SEM is thus a useful tool for imaging large mammalian cells
      in their entirety at resolutions in the nanometer range.

PMID- 19116172
TI  - Phylogenetic utility of nuclear nitrate reductase: a multi-locus comparison of
      nuclear and chloroplast sequence data for inference of relationships among
      American Lycieae (Solanaceae).
AB  - There has been considerable interest and research into the benefits of multiple
      low-copy nuclear regions for phylogenetic studies at low taxonomic levels. In
      this study, the phylogenetic utility of DNA sequence data from two low-copy
      nuclear genes, nitrate reductase (NIA) and granule-bound starch synthase I
      (GBSSI), was compared with data from nuclear ribosomal ITS and the cpDNA spacers
      trnT-trnF and trnD-trnT across 33 closely related taxa in tribe Lycieae
      (Solanaceae). The NIA data (introns 1-2) had the most parsimony-informative
      characters, with over twice the number provided by GBSSI, but NIA also had
      greater homoplasy. Although gene trees were generally concordant across the four
      regions, there were some notable areas of incongruence, suggesting both
      incomplete lineage sorting as well as possible reticulate origins.

PMID- 19116174
TI  - Chronic oral methylphenidate induces post-treatment impairment in recognition and
      spatial memory in adult rats.
AB  - Recent pre-clinical research has indicated that chronic treatment with
      methylphenidate (Ritalin) in young animals can result in lasting and potentially
      detrimental alterations in brain function that can persist into adulthood.
      Chronic methylphenidate-induced neuronal alterations may result in behavior and
      cognitive deficits that include increases in behavioral responses and impairment
      in recognition memory. This study compared the cognitive consequences following
      chronic treatment with two doses (5 and 10 mg/kg) of methylphenidate on
      recognition and spatial memory in adult male Long-Evans rats using an established
      oral dosing procedure. The animals were then tested in the Object Recognition
      test at 14 days post treatment and the Object Placement test at 21 days post
      treatment. The results indicate that repeated exposure to oral methylphenidate
      impaired the performance of rats in these tests. The current findings add to
      recent research demonstrating negative consequences in rats pre-treated with
      methylphenidate, and extend previous findings to include deficits in spatial
      recognition memory.

PMID- 19116175
TI  - Role of the Botrytis cinerea FKBP12 ortholog in pathogenic development and in
      sulfur regulation.
AB  - The functional characterization of the FKBP12 encoding gene from the
      phytopathogenic fungus Botrytis cinerea was carried out. B. cinerea genome
      sequence owns a single ortholog, named BcFKBP12, encoding a FK506-binding protein
      of 12kDa. BcFKBP12 mediates rapamycin sensitivity both in B. cinerea and in
      Saccharomyces cerevisiae, a property unique to FKBP12 proteins, probably via the
      inhibition of the protein kinase TOR (target of rapamycin). The relative
      abundance of the prolyl isomerase appeared to be regulated and increased in
      response to the presence of extracellular nutrients. Surprisingly, the BcFKBP12
      deletion did not affect the pathogenic development of the strain B05.10, while it
      was reported to cause a reduction of the virulence of the strain T4. We report
      for the first time the BcFKBP12 involvement in the sulfur repression of the
      synthesis of a secreted serine protease. Rapamycin treatment did not relieve the
      sulfur repression of the reporter system in the wild-type strain. Thus BcFKBP12
      may participate in sulfur regulation and its contribution seems to be independent
      of TOR.

PMID- 19116176
TI  - Distorted Mendelian transmission as a function of genetic background in Rai1
      haploinsufficient mice.
AB  - The retinoic acid induced 1 gene (RAI1) is the primary causative gene for Smith
      Magenis syndrome (SMS). Chromosomal deletion encompassing RAI1 or mutation in
      RAI1 is responsible for the majority of SMS features. Mouse models with targeted
      disruption of Rai1 have recapitulated overt SMS phenotypes, including
      craniofacial abnormalities, obesity, and neurobehavioral anomalies. Penetrance
      and expressivity of most phenotypes in mice were incomplete due to the mixed
      genetic background in which they were created. While increased penetrance of
      craniofacial phenotypes was observed in relatively homogeneous backgrounds, the
      effect of Rai1 haploinsufficiency on breeding outcome and fitness has not been
      studied. We analyzed mating results of Rai1+/- mice in a pure C57BL/6J background
      (>or=N10 generations). A significant distortion (P<0.05) of Mendelian
      transmission ratio with skewing against Rai1+/- mice was observed. Consequently,
      a decreased number of Rai1+/- pups and no Rai1-/- pups were obtained from all the
      breeding pairs. The decreased yield of Rai1+/- pups precluded penetrance studies
      of other phenotypes in these mice. However, when Rai1+/- alleles were transferred
      to a slightly variable (approximately 1% 129/approximately 99% C57BL/6J) genetic
      background expected numbers of Rai1+/- pups were obtained. Our results indicate
      that selection against Rai1-haploinsufficient alleles is governed primarily by
      modifier genes. Our data show that genetic background or modifier genes also
      significantly contribute to the severity of the phenotypes in SMS mouse models,
      mirroring the phenotypic variation observed in humans with Smith-Magenis syndrome
      and support the need for investigation of modifier loci for both single gene and
      complex genetic syndromes.

PMID- 19116173
TI  - Neural correlates of learning and working memory in the primate posterior
      parietal cortex.
AB  - The posterior parietal cortex has been traditionally associated with coordinate
      transformations necessary for interaction with the environment and with visual
      spatial attention. More recently, involvement of posterior parietal cortex in
      other cognitive functions such as working memory and task learning has become
      evident. Neurophysiological experiments in non-human primates and human imaging
      studies have revealed neural correlates of memory and learning at the single
      neuron and at the brain network level. During working memory, posterior parietal
      neurons continue to discharge and to represent stimuli that are no longer
      present. This activation resembles the responses of prefrontal neurons, although
      important differences have been identified in terms of the ability to resist
      stimulation by distracting stimuli, which is more evident in the prefrontal than
      the posterior parietal cortex. Posterior parietal neurons also become active
      during tasks that require the organization of information into larger structured
      elements and their activity is modulated according to learned context-dependent
      rules. Neural correlates of learning can be observed in the mean discharge rate
      and spectral power of neuronal spike trains after training to perform new task
      sets or rules. These findings demonstrate the importance of posterior parietal
      cortex in brain networks mediating working memory and learning.

PMID- 19116177
TI  - Maternal and perinatal outcome in teenage pregnancies in Sudan.

PMID- 19116178
TI  - Low-molecular-weight heparin versus intravenous immunoglobulin for recurrent
      abortion associated with antiphospholipid antibody syndrome.
AB  - OBJECTIVE: To compare low-molecular-weight (LMW) heparin plus low-dose aspirin
      with intravenous immunoglobulin (IVIG) in the treatment of antiphospholipid
      antibody syndrome in women with recurrent spontaneous abortions before 10 weeks
      of gestation. METHOD: This prospective, multicenter trial conducted between 2002
      and 2006 included 85 patients aged 18-39 years. The women were allocated randomly
      to receive LMW heparin plus low-dose aspirin, or IVIG. Data were compared using
      the t test and Fisher exact test. RESULTS: The women treated with LMW heparin
      plus low-dose aspirin had a higher rate of live births than those treated with
      IVIG (P=0.003). Of those who completed the study, 29/40 (72.5%) and 15/38
      (39.5%), respectively, had live births. Intent-to-treat analysis revealed a
      significant difference between the 2 groups (OR 1.802; 95%CI, 1.14-2.84;
      P=0.007). CONCLUSIONS: LMW heparin plus low-dose aspirin resulted in a higher
      live birth rate than IVIG in the treatment of antiphospholipid antibody syndrome
      in women with recurrent abortion.

PMID- 19116179
TI  - Betanodavirus non-structural protein B2: A novel necrotic death factor that
      induces mitochondria-mediated cell death in fish cells.
AB  - The Betanodavirus non-structural protein B2 plays a role in silencing RNA
      interference (RNAi), which mediated regulation of animal and plant innate immune
      responses, but little is known regarding the role of B2 in cell death. The
      present study examined the effects of B2 on mitochondria-mediated necrotic cell
      death in grouper liver (GL-av) cells. B2 was expressed at 12 h post-infection
      (pi), with increased expression between 24 and 72 h pi by Western blot. B2 was
      transiently expressed to investigate possible novel protein functions. Transient
      expression of B2 in GL-av cells resulted in apoptotic cell features and positive
      TUNEL assays (28%) at 24 h post-transfection (pt). During mechanistic studies of
      cell death, B2 upregulated expression of the proapoptotic gene Bax (2.8 fold at
      48 h pt) and induced loss of mitochondria membrane potential (MMP) but not
      mitochondrial cytochrome c release. Furthermore, over expression of Bcl-2 family
      member zfBcl-xL effectively prevented B2-induced, mitochondria-mediated necrotic
      cell death. Finally, using RNA interference to reduce B2 expression, both B2 and
      Bax expression were downregulated and RGNNV-infected cells were rescued from
      secondary necrosis. Taken together, our results suggest that B2 upregulates Bax
      and triggers mitochondria-mediated necrotic cell death independent of cytochrome
      c release.

PMID- 19116180
TI  - Cardiac MR1 and peripartum cardiomyopathy.
AB  - Cardiac MRI brings great benefits in the comprehension of the mechanism(s)
      involved in the genesis of peripartum cardiomyopathy (PPC). Cardiac MRI may also
      procure prognostic information. Because this is a rare affection, it seems
      necessary to systematically study PPC with this safe, non invasive and reliable
      tool. Creation of a multicentric register with a systematic application of
      cardiac MRI in this pathology may be considered.

PMID- 19116181
TI  - Hypothyroxinemia and effectiveness of thyroxin supplementation in very low birth
      weight infants with abdominal distension and poor weight gain.
AB  - BACKGROUND: Very low birth weight (VLBW) infants sometimes develop abdominal
      distension and poor weight gain. The influence of thyroid function on these
      symptoms in VLBW infants has not been reported. METHODS: In a retrospective
      study, 18 VLBW infants whose abdominal distension and poor weight gain did not
      improve with standard treatment were enrolled as subjects. Serum levels of free
      thyroxin (fT(4)) and thyroid stimulating hormone (TSH) were measured. Subjects
      with serum fT(4) levels less than 1.3 ng/dl received thyroxin supplementation.
      Another 18 VLBW infants were recruited as age- and weight-matched controls. We
      compared degree of intestinal dilation on X-ray, weight gain, and quantity of
      milk tolerated before and after starting thyroxin supplementation in the subjects
      and the controls. RESULTS: All subjects had serum fT(4) levels less than 1.3
      ng/dl (mean, 0.72 ng/dl). TSH values varied widely and were less than 8 microU/ml
      in 12 subjects. Therefore, all subjects received thyroxin supplementation; after
      starting this, mean serum fT(4) level increased significantly to 1.31 ng/dl. In
      parallel with fT(4) increase, intestinal dilation improved in 16 of 18 subjects
      (mean grade of dilation decreased from 2.8 to 1.6). Weight gain and quantity of
      tolerated milk were significantly increased with thyroxin supplementation in all
      and 17 of the 18 subjects, respectively. CONCLUSIONS: Thyroxin supplementation
      was effective in improving abdominal symptoms in VLBW infants whose serum fT(4)
      level was less than 1.3 ng/dl.

PMID- 19116182
TI  - CB1 receptor knockout mice are hyporesponsive to the behavior-stimulating actions
      of d-amphetamine: role of mGlu5 receptors.
AB  - Blockade of the cannabinoid CB1 receptors (CB1R) has been shown to reduce
      psychostimulant-induced hyperactivity, an effect that we sought to further
      characterize here. The CB1R antagonist SR141716A dose-dependently decreased d
      amphetamine-induced hyperactivity.Also, d-amphetamine-induced hyperlocomotion was
      reduced in CB1R knockout (KO) mice. However, CB1R KO and wild-type mice showed a
      similar d-amphetamine-induced increase in nucleus accumbens DA release. Hence, we
      investigated whether CB1R antagonism/invalidation reduces d-amphetamine-induced
      hyperlocomotion through a mechanism involving changes in glutamatergic
      neurotransmission. Blockade of metabotropic-glutamate-receptors-5 (mGluR5)with
      MPEP, but not blockade of N-methyl-D-aspartate-receptors (NMDA) with MK
      801,restored to a great extent the blunted d-amphetamine-induced hyperlocomotion
      seen after CB1R antagonism/invalidation. Thus, hyporesponsiveness to the
      psychostimulant effects of d-amphetamine as a result of CB1R
      antagonism/invalidation is not due to an ensuing decrease in d-amphetamine
      induced DA release in the nucleus accumbens, but rather due to a
      hyperglutamatergic state and facilitation of glutamatergic neurotransmission at
      the mGlu5, but not NMDA, receptors.

PMID- 19116184
TI  - Statistical based impulsive noise removal in digital radiography.
AB  - A new filter to restore radiographic images corrupted by impulsive noise is
      proposed. It is based on a switching scheme where all the pulses are first
      detected and then corrected through a median filter. The pulse detector is based
      on the hypothesis that the major contribution to image noise is given by the
      photon counting process, with some pixels corrupted by impulsive noise. Such
      statistics is described by an adequate mixture model. The filter is also able to
      reliably estimate the sensor gain. Its operation has been verified on both
      synthetic and real images; the experimental results demonstrate the superiority
      of the proposed approach in comparison with more traditional methods.

PMID- 19116183
TI  - Electrophysiological characterization of the effects of asenapine at 5-HT(1A), 5
      HT(2A), alpha(2)-adrenergic and D(2) receptors in the rat brain.
AB  - Asenapine is a psychopharmacologic agent being developed for schizophrenia and
      bipolar disorder. This study electrophysiologically characterized the in vivo
      effects of asenapine at dorsal raphe nucleus (DRN) and hippocampus serotonin-1A
      (5-HT(1A)), ventral tegmental area D(2), locus coeruleus 5-HT(2A,) and alpha(2)
      adrenergic receptors in anesthetized rats. Asenapine displayed potent
      antagonistic activity at alpha(2)-adrenoceptors (ED(50), 85+/-2 microg/kg), 5
      HT(2A) (ED(50), 75+/-2 microg/kg) and D(2) receptors (ED(50), 40+/-2 microg/kg)
      as evidenced by its reversal of clonidine-, DOI-, and apomorphine-induced
      inhibition of norepinephrine and dopamine neurons. In contrast, asenapine acted
      as a partial agonist at 5-HT(1A) receptors in DRN and hippocampus, as indicated
      by blockade of its inhibitory effect on neuronal firing by the 5-HT(1A)
      antagonist WAY 100635 and the partial inhibition of the suppressant action of 5
      HT when co-applied by microiontophoresis. These results confirm that asenapine
      displays potent antagonistic activity at 5-HT(2A), D(2), alpha(2)-adrenergic
      receptors and provide evidence to support its 5-HT(1A) partial agonistic
      activity.

PMID- 19116185
TI  - Reconstruction from uniformly attenuated SPECT projection data using the DBH
      method.
AB  - An algorithm was developed for the 2-D reconstruction of truncated and
      nontruncated uniformly attenuated data acquired from single photon emission
      computed tomography (SPECT). The algorithm is able to reconstruct data from half
      scan (180 ( degrees ) ) and short-scan (180 ( degrees ) +fan angle) acquisitions
      for parallel- and fan-beam geometries, respectively, as well as data from full
      scan (360 ( degrees )) acquisitions. The algorithm is a derivative,
      backprojection, and Hilbert transform (DBH) method, which involves the
      backprojection of differentiated projection data followed by an inversion of the
      finite weighted Hilbert transform. The kernel of the inverse weighted Hilbert
      transform is solved numerically using matrix inversion. Numerical simulations
      confirm that the DBH method provides accurate reconstructions from half-scan and
      short-scan data, even when there is truncation. However, as the attenuation
      increases, finer data sampling is required.

PMID- 19116187
TI  - On concise 3-D simple point characterizations: a marching cubes paradigm.
AB  - The centerlines of tubular structures are useful for medical image visualization
      and computer-aided diagnosis applications. They can be effectively extracted by
      using a thinning algorithm that erodes an object layer by layer until only a
      skeleton is left. An object point is "simple" and can be safely deleted only if
      the resultant image is topologically equivalent to the original. Numerous
      characterizations of 3-D simple points based on digital topology already exist.
      However, little work has been done in the context of marching cubes (MC). This
      paper reviews several concise 3-D simple point characterizations in a MC
      paradigm. By using the Euler characteristic and a few newly observed properties
      in the context of connectivity-consistent MC, we present concise and more self
      explanatory proofs. We also present an efficient method for computing the Euler
      characteristic locally for MC surfaces. Performance evaluations on different
      implementations are conducted on synthetic data and multidetector computed
      tomography examination of virtual colonoscopy and angiography.

PMID- 19116186
TI  - Combined optical imaging and mammography of the healthy breast: optical contrast
      derived from breast structure and compression.
AB  - In this paper, we report new progress in developing the instrument and software
      platform of a combined X-ray mammography/diffuse optical breast imaging system.
      Particularly, we focus on system validation using a series of balloon phantom
      experiments and the optical image analysis of 49 healthy patients. Using the
      finite-element method for forward modeling and a regularized Gauss-Newton method
      for parameter reconstruction, we recovered the inclusions inside the phantom and
      the hemoglobin images of the human breasts. An enhanced coupling coefficient
      estimation scheme was also incorporated to improve the accuracy and robustness of
      the reconstructions. The recovered average total hemoglobin concentration (HbT)
      and oxygen saturation (SO2) from 68 breast measurements are 16.2 microm and 71%,
      respectively, where the HbT presents a linear trend with breast density. The low
      HbT value compared to literature is likely due to the associated mammographic
      compression. From the spatially co-registered optical/X-ray images, we can
      identify the chest-wall muscle, fatty tissue, and fibroglandular regions with an
      average HbT of 20.1+/-6.1 microm for fibroglandular tissue, 15.4+/-5.0 microm for
      adipose, and 22.2+/-7.3 microm for muscle tissue. The differences between
      fibroglandular tissue and the corresponding adipose tissue are significant (p <
      0.0001). At the same time, we recognize that the optical images are influenced,
      to a certain extent, by mammographical compression. The optical images from a
      subset of patients show composite features from both tissue structure and
      pressure distribution. We present mechanical simulations which further confirm
      this hypothesis.

PMID- 19116188
TI  - The BoneXpert method for automated determination of skeletal maturity.
AB  - Bone age rating is associated with a considerable variability from the human
      interpretation, and this is the motivation for presenting a new method for
      automated determination of bone age (skeletal maturity). The method, called
      BoneXpert, reconstructs, from radiographs of the hand, the borders of 15 bones
      automatically and then computes "intrinsic" bone ages for each of 13 bones
      (radius, ulna, and 11 short bones). Finally, it transforms the intrinsic bone
      ages into Greulich Pyle (GP) or Tanner Whitehouse (TW) bone age. The bone
      reconstruction method automatically rejects images with abnormal bone morphology
      or very poor image quality. From the methodological point of view, BoneXpert
      contains the following innovations: 1) a generative model (active appearance
      model) for the bone reconstruction; 2) the prediction of bone age from shape,
      intensity, and texture scores derived from principal component analysis; 3) the
      consensus bone age concept that defines bone age of each bone as the best
      estimate of the bone age of the other bones in the hand; 4) a common bone age
      model for males and females; and 5) the unified modelling of TW and GP bone age.
      BoneXpert is developed on 1559 images. It is validated on the Greulich Pyle atlas
      in the age range 2-17 years yielding an SD of 0.42 years [0.37; 0.47] 95% conf,
      and on 84 clinical TW-rated images yielding an SD of 0.80 years [0.68; 0.93] 95%
      conf. The precision of the GP bone age determination (its ability to yield the
      same result on a repeated radiograph) is inferred under suitable assumptions from
      six longitudinal series of radiographs. The result is an SD on a single
      determination of 0.17 years [0.13; 0.21] 95% conf.

PMID- 19116189
TI  - Performance of MAP reconstruction for hot lesion detection in whole-body PET/CT:
      an evaluation with human and numerical observers.
AB  - For positron emission tomography (PET) imaging, different reconstruction methods
      can be applied, including maximum likelihood (ML ) and maximum a posteriori (MAP)
      reconstruction. Postsmoothed ML images have approximately position and object
      independent spatial resolution, which is advantageous for (semi-) quantitative
      analysis. However, the complex object dependent smoothing obtained with MAP might
      yield improved noise characteristics, beneficial for lesion detection. In this
      contribution, MAP and postsmoothed ML are compared for hot spot detection by
      human observers and by the channelized Hotelling observer (CHO). The study design
      was based on the "multiple alternative forced choice" approach. For the MAP
      reconstruction, the relative difference prior was used. For postsmoothed ML, a
      Gaussian smoothing kernel was used. Both the human observers and the CHO
      performed slightly better on MAP images than on postsmoothed ML images. The
      average CHO performance was similar to the best human performance. The CHO was
      then applied to evaluate the performance of priors with reduced penalty for large
      differences. For these priors, a poorer detection performance was obtained.

PMID- 19116190
TI  - In situ characterization of the degradation of PLGA microspheres in hyaluronic
      acid hydrogels by optical coherence tomography.
AB  - The polymeric implant material poly(lactide-co-glycolide) (PLGA) degrades by a
      process of bulk degradation, which allows it to be used for the controlled
      release of therapeutic molecules from implants and microspheres. The temporal
      characterization of PLGA microsphere degradation has been limited by the need to
      destructively monitor the samples at each time point. In this study, a
      noninvasive imaging technology, optical coherence tomography (OCT), was utilized
      to characterize the in situ degradation of PLGA microspheres suspended within
      photo-crosslinked hyaluronic acid (HA) hydrogels. Microspheres with differing
      degradation rates were loaded with bovine serum albumin (BSA) as a marker
      protein, and temporal release of protein was correlated with morphological
      changes observed during 3-D OCT imaging. As proof-of-principle, a microsphere
      loaded hydrogel scaffold was implanted in a modified rat calvarial critical size
      defect model and imaged using OCT. This animal model presents the opportunity to
      monitor microsphere degradation over time in living animals.

PMID- 19116191
TI  - Extrapolation and correlation (EXTRACT): a new method for motion compensation in
      MRI.
AB  - A postprocessing technique is proposed for the correction of both translational
      and rotational motion artifacts in magnetic resonance imaging (MRI). The method
      consists of two steps: 1) k-space extrapolation to generate a motion-free
      reference, followed by 2) correlation with actual data to estimate motion. In
      this paper, two different extrapolation methods were investigated for the purpose
      of motion estimation: edge enhancement and finite-support solution. It was found
      that finite-support solution performs better near the k-space center, while the
      edge enhancement method is superior in the outer k-space regions. Therefore, a
      combination of the two methods was employed to generate a motion-free reference,
      whose correlations with the acquired data can subsequently determine the object
      motion. Motion compensation was demonstrated in simulation and in vivo MR
      experiments. The technique is shown to be robust against noise and various types
      of motion.

PMID- 19116192
TI  - User-agent cooperation in multiagent IVUS image segmentation.
AB  - Automated interpretation of complex images requires elaborate knowledge and model
      based image analysis, but often needs interaction with an expert as well. This
      research describes expert interaction with a multiagent image interpretation
      system using only a restricted vocabulary of high-level user interactions. The
      aim is to minimize inter- and intra-observer variability by keeping the total
      number of interactions as low and simple as possible. The multiagent image
      interpretation system has elaborate high-level knowledge-based control over low
      level image segmentation algorithms. Agents use contextual knowledge to keep the
      number of interactions low but, when in doubt, present the user with the most
      likely interpretation of the situation. The user, in turn, can correct,
      supplement, and/or confirm the results of image-processing agents. This is done
      at a very high level of abstraction such that no knowledge of the underlying
      segmentation methods, parameters or agent functioning is needed. High-level
      interaction thereby replaces more traditional contour correction methods like
      inserting points and/or (re)drawing contours. This makes it easier for the user
      to obtain good results, while inter- and intra-observer variability are kept
      minimal, since the image segmentation itself remains under control of image
      processing agents. The system has been applied to intravascular ultrasound (IVUS)
      images. Experiments show that with an average of 2-3 high-level user interactions
      per correction, segmentation results substantially improve while the variation is
      greatly reduced. The achieved level of accuracy and repeatability is equivalent
      to that of manual drawing by an expert.

PMID- 19116193
TI  - Highly undersampled magnetic resonance image reconstruction via homotopic l(0) 
      minimization.
AB  - In clinical magnetic resonance imaging (MRI), any reduction in scan time offers a
      number of potential benefits ranging from high-temporal-rate observation of
      physiological processes to improvements in patient comfort. Following recent
      developments in compressive sensing (CS) theory, several authors have
      demonstrated that certain classes of MR images which possess sparse
      representations in some transform domain can be accurately reconstructed from
      very highly undersampled K-space data by solving a convex l(1) -minimization
      problem. Although l(1)-based techniques are extremely powerful, they inherently
      require a degree of over-sampling above the theoretical minimum sampling rate to
      guarantee that exact reconstruction can be achieved. In this paper, we propose a
      generalization of the CS paradigm based on homotopic approximation of the l(0)
      quasi-norm and show how MR image reconstruction can be pushed even further below
      the Nyquist limit and significantly closer to the theoretical bound. Following a
      brief review of standard CS methods and the developed theoretical extensions,
      several example MRI reconstructions from highly undersampled K-space data are
      presented.

PMID- 19116194
TI  - Automated method for improving system performance of computer-aided diagnosis in
      breast ultrasound.
AB  - The purpose of this research was to demonstrate the feasibility of a computerized
      auto-assessment method in which a computer-aided diagnosis (CADx) system itself
      provides a level of confidence for its estimate for the probability of malignancy
      for each radiologist-identified lesion. The computer performance was assessed
      within a leave-one-case-out protocol using a database of sonographic images from
      542 patients (19% cancer prevalence). We investigated the potential of computer
      derived confidence levels both as 1) an output aid to radiologists and 2) as an
      automated method to improve the computer classification performance-in the task
      of differentiating between cancerous and benign lesions for the entire database.
      For the former, the CADx classification performance was assessed within ranges of
      confidence levels. For the latter, the computer-derived confidence levels were
      used in the determination of the computer-estimated probability of malignancy for
      each actual lesion based on probabilities obtained from different views. The use
      of this auto-assessment method resulted in the modest but statistically
      significant increase in the area under the receiver operating characteristic
      (ROC) curve (AUC value) of 0.01 with respect to the performance obtained using
      the "traditional" CADx approach, increasing the AUC value from 0.89 to 0.90 ( p 
      value 0.03). We believe that computer-provided confidence levels may be helpful
      to radiologists who are using CADx output in diagnostic image interpretation as
      well as for automated improvement of the CADx classification for cancer.

PMID- 19116195
TI  - Color compensation of multicolor fish images.
AB  - Multicolor fluorescence in situ hybridization (M-FISH) techniques provide color
      karyotyping that allows simultaneous analysis of numerical and structural
      abnormalities of whole human chromosomes. Chromosomes are stained combinatorially
      in M-FISH. By analyzing the intensity combinations of each pixel, all chromosome
      pixels in an image are classified. Due to the overlap of excitation and emission
      spectra and the broad sensitivity of image sensors, the obtained images contain
      crosstalk between the color channels. The crosstalk complicates both visual and
      automatic image analysis and may eventually affect the classification accuracy in
      M-FISH. The removal of crosstalk is possible by finding the color compensation
      matrix, which quantifies the color spillover between channels. However, there
      exists no simple method of finding the color compensation matrix from
      multichannel fluorescence images whose specimens are combinatorially hybridized.
      In this paper, we present a method of calculating the color compensation matrix
      for multichannel fluorescence images whose specimens are combinatorially stained.

PMID- 19116196
TI  - Nonrigid registration of joint histograms for intensity standardization in
      magnetic resonance imaging.
AB  - A major disadvantage of magnetic resonance imaging (MRI) compared to other
      imaging modalities like computed tomography is the fact that its intensities are
      not standardized. Our contribution is a novel method for MRI signal intensity
      standardization of arbitrary MRI scans, so as to create a pulse sequence
      dependent standard intensity scale. The proposed method is the first approach
      that uses the properties of all acquired images jointly (e.g., T1- and T2
      weighted images). The image properties are stored in multidimensional joint
      histograms. In order to normalize the probability density function (pdf) of a
      newly acquired data set, a nonrigid image registration is performed between a
      reference and the joint histogram of the acquired images. From this matching a
      nonparametric transformation is obtained, which describes a mapping between the
      corresponding intensity spaces and subsequently adapts the image properties of
      the newly acquired series to a given standard. As the proposed intensity
      standardization is based on the probability density functions of the data sets
      only, it is independent of spatial coherence or prior segmentations of the
      reference and current images. Furthermore, it is not designed for a particular
      application, body region or acquisition protocol. The evaluation was done using
      two different settings. First, MRI head images were used, hence the approach can
      be compared to state-of-the-art methods. Second, whole body MRI scans were used.
      For this modality no other normalization algorithm is known in literature. The
      Jeffrey divergence of the pdfs of the whole body scans was reduced by 45%. All
      used data sets were acquired during clinical routine and thus included
      pathologies.

PMID- 19116197
TI  - Automatic quantification of joint space narrowing and erosions in rheumatoid
      arthritis.
AB  - Rheumatoid arthritis (RA) is a chronic disease that affects and potentially
      destroys the joints of the appendicular skeleton. The precise and reproducible
      quantification of the progression of joint space narrowing and the erosive bone
      destructions caused by RA is crucial during treatment and in imaging biomarkers
      in clinical trials. Current manual scoring methods exhibit high interreader
      variability, even after intensive training, and thus, impede the efficient
      monitoring of the disease. We propose a fully automatic quantitative assessment
      of the radiographic changes that result from RA, to increase the accuracy,
      reproducibility, and speed of image interpretation. Initial joint location
      estimates are obtained by local linear mappings based on texture features. Bone
      contours are delineated by active shape models comprised of statistical models of
      bone shape and local texture. These models are refined by snakes which increase
      the accuracy and allow for a fitting of pathological deviations from the training
      population. The method then measures joint space widths and detects erosions on
      the bone contour. Joint space widths are measured with a coefficient of variation
      of 2%-7% for repeated measurements and erosion detection exhibits an area under
      the receiver operating characteristic (ROC) curve of 0.89. Model landmarks serve
      as a reference system along the contour. These landmarks enable the definition of
      joint regions and more specific follow-up monitoring. The automatic
      quantification allows for a remote analysis, relevant for multicenter clinical
      trials, and reduces the workload of clinical experts since parts of the process
      can be managed by nonexpert personnel.

PMID- 19116198
TI  - Study of image quality of superimposed projection using multiple projectors.
AB  - In this correspondence, we discuss the quality of images realized by a recently
      proposed method of generating a high-resolution image by superimposing multiple
      low-resolution images projected by different projectors. We show several
      fundamental properties of this method: 1) the accuracy of the image realization
      (e.g., resolution of the realized image) is heavily affected by the structures of
      the images to be realized, and 2) there is a tradeoff between the image quality
      and the maximum brightness of the images to be realized. These are properties
      peculiar to multiprojector super-resolution and are in contrast with multicamera
      super-resolution. The results will be helpful in evaluating the usefulness of the
      method.

PMID- 19116199
TI  - High-fidelity data embedding for image annotation.
AB  - High fidelity is a demanding requirement for data hiding, especially for images
      with artistic or medical value. This correspondence proposes a high-fidelity
      image watermarking for annotation with robustness to moderate distortion. To
      achieve the high fidelity of the embedded image, we introduce a visual perception
      model that aims at quantifying the local tolerance to noise for arbitrary
      imagery. Based on this model, we embed two kinds of watermarks: a pilot watermark
      that indicates the existence of the watermark and an information watermark that
      conveys a payload of several dozen bits. The objective is to embed 32 bits of
      metadata into a single image in such a way that it is robust to JPEG compression
      and cropping. We demonstrate the effectiveness of the visual model and the
      application of the proposed annotation technology using a database of challenging
      photographic and medical images that contain a large amount of smooth regions.

PMID- 19116200
TI  - Efficient minimization method for a generalized total variation functional.
AB  - Replacing the l(2) data fidelity term of the standard Total Variation (TV)
      functional with an l(1) data fidelity term has been found to offer a number of
      theoretical and practical benefits. Efficient algorithms for minimizing this l(1)
      TV functional have only recently begun to be developed, the fastest of which
      exploit graph representations, and are restricted to the denoising problem. We
      describe an alternative approach that minimizes a generalized TV functional,
      including both l(2)-TV and l(1)-TV as special cases, and is capable of solving
      more general inverse problems than denoising (e.g., deconvolution). This
      algorithm is competitive with the graph-based methods in the denoising case, and
      is the fastest algorithm of which we are aware for general inverse problems
      involving a nontrivial forward linear operator.

PMID- 19116201
TI  - Interpolation artifacts in sub-pixel image registration.
AB  - We consider the problem of registering (aligning) two images to sub-pixel
      accuracy by optimization of objective functions constructed from the images'
      intensity values. We show that some widely used interpolation methods can
      introduce multiple local optima in the energy of the interpolated image which, if
      not counter-balanced by other terms, can cause local optima in registration
      objective functions including the sum of squared differences, cross correlation,
      and mutual information. We discuss different solutions to address the problem
      based on high degree B-spline interpolation, low pass filtering the images, and
      stochastic integration. Numerical examples using synthetic and real signals and
      images are shown.

PMID- 19116202
TI  - Normal hepatic cell surface localization of the high density lipoprotein
      receptor, scavenger receptor class B, type I, depends on all four PDZ domains of
      PDZK1.
AB  - PDZK1 is a four PDZ domain-containing scaffold protein that binds to scavenger
      receptor class B, type I (SR-BI), the high density lipoprotein receptor, by its
      first PDZ domain (PDZ1). PDZK1 knock-out mice exhibit a >95% decrease in hepatic
      SR-BI protein and consequently an approximately 70% increase in plasma
      cholesterol in abnormally large high density lipoprotein particles. These defects
      are corrected by hepatic overexpression of full-length PDZK1 but not the PDZ1
      domain alone, which partially restores SR-BI protein abundance but not cell
      surface expression or function. We have generated PDZK1 knock-out mice with
      hepatic expression of four PDZK1 transgenes encoding proteins with nested C
      terminal truncations: pTEM, which lacks the three C-terminal residues (putative
      PDZ-binding motif), and PDZ1.2, PDZ1.2.3, or PDZ1.2.3.4, which contain only the
      first two, three, or four N-terminal PDZ domains, respectively, but not the
      remaining C-terminal sequences. Hepatic overexpression of pTEM restored normal
      hepatic SR-BI abundance, localization, and function. Hepatic overexpression of
      PDZ1.2 or PDZ1.2.3 partially restored SR-BI abundance ( approximately 12 or
      approximately 30% of wild type, respectively) but did not (PDZ1.2) or only
      slightly (PDZ1.2.3) restored hepatic SR-BI cell surface localization and
      function. Hepatic overexpression of PDZ1.2.3.4 completely restored SR-BI protein
      abundance, cell surface expression, and function (normalization of plasma
      cholesterol levels). Thus, all four PDZ domains in PDZK1, but not PDZ1-3 alone,
      are sufficient for its normal control of the abundance, localization, and
      therefore function of hepatic SR-BI, whereas the residues C-terminal to the PDZ4
      domain, including the C-terminal putative PDZ-binding domain, are not required.

PMID- 19116203
TI  - Fluorescence mapping of the open complex of yeast mitochondrial RNA polymerase.
AB  - The mitochondrial RNA polymerase (mtRNAP) of Saccharomyces cerevisiae, consisting
      of a complex of Rpo41 and Mtf1, is homologous to the phage single polypeptide
      T7/T3 RNA polymerases. The yeast mtRNAP recognizes a conserved nonanucleotide
      sequence to initiate specific transcription. In this work, we have defined the
      region of the nonanucleotide that is melted by the mtRNAP using 2-aminopurine
      (2AP) fluorescence that is sensitive to changes in base stacking interactions. We
      show that mtRNAP spontaneously melts the promoter from -4 to +2 forming a bubble
      around the transcription start site at +1. The location and size of the DNA
      bubble in this open complex of the mtRNAP closely resembles that of the T7 RNA
      polymerase. We show that DNA melting requires the simultaneous presence of Rpo41
      and Mtf1. Adding the initiating nucleotide ATP does not expand the size of the
      initially melted DNA, but the initiating nucleotide differentially affects base
      stacking interactions at -1 and -2. Thus, the promoter structure upstream of the
      transcription start site is slightly rearranged during early initiation from its
      structure in the pre-initiation stage. Unlike on the duplex promoter, Rpo41 alone
      was able to form a competent open complex on a pre-melted promoter. The results
      indicate that Rpo41 contains the elements for recognizing the melted promoter
      through interactions with the template strand. We propose that Mtf1 plays a role
      in base pair disruption during the early stages of open complex formation.

PMID- 19116204
TI  - A common human micro-opioid receptor genetic variant diminishes the receptor
      signaling efficacy in brain regions processing the sensory information of pain.
AB  - The single nucleotide polymorphism 118A>G of the human micro-opioid receptor gene
      OPRM1, which leads to an exchange of the amino acid asparagine (N) to aspartic
      acid (D) at position 40 of the extracellular receptor region, alters the in vivo
      effects of opioids to different degrees in pain-processing brain regions. The
      most pronounced N40D effects were found in brain regions involved in the sensory
      processing of pain intensity. Using the mu-opioid receptor-specific agonist
      DAMGO, we analyzed the micro-opioid receptor signaling, expression, and binding
      affinity in human brain tissue sampled postmortem from the secondary
      somatosensory area (SII) and from the ventral posterior part of the lateral
      thalamus, two regions involved in the sensory processing and transmission of
      nociceptive information. We show that the main effect of the N40D micro-opioid
      receptor variant is a reduction of the agonist-induced receptor signaling
      efficacy. In the SII region of homo- and heterozygous carriers of the variant
      118G allele (n=18), DAMGO was only 62% as efficient (p=0.002) as in homozygous
      carriers of the wild-type 118A allele (n=15). In contrast, the number of
      [3H]DAMGO binding sites was unaffected. Hence, the micro-opioid receptor G
      protein coupling efficacy in SII of carriers of the 118G variant was only 58% as
      efficient as in homozygous carriers of the 118A allele (p<0.001). The thalamus
      was unaffected by the OPRM1 118A>G SNP. In conclusion, we provide a molecular
      basis for the reduced clinical effects of opioid analgesics in carriers of mu
      opioid receptor variant N40D.

PMID- 19116205
TI  - Mutations in subdomain B of the minichromosome maintenance (MCM) helicase affect
      DNA binding and modulate conformational transitions.
AB  - Minichromosome maintenance (MCM) proteins are believed to provide the replicative
      helicase activity in eukaryotes and archaea. The single MCM orthologue from
      Methanothermobacter thermautotrophicus (MthMCM) has been extensively
      characterized as a model of the eukaryotic heterohexameric MCM complex. MthMCM
      forms high molecular weight complexes in solution consistent with a dodecamer.
      Visualization of this complex by electron microscopy suggests that single and
      double heptameric or hexameric rings can form. We have mutated two arginine
      residues (Arg-137, Arg-160) in the N-terminal subdomain B of MthMCM based on
      their apparent potential to form inter-ring hydrogen bonds. Both the single R137A
      and the double R137A,R160A mutants were characterized by a combination of
      biophysical, biochemical, and electron microscopy techniques. Biophysical
      analysis coupled with electron microscopy studies shows that the R137A mutant
      forms a double heptameric ring, whereas the R137A,R160A protein assembles as a
      single heptamer. They both show a defect in DNA binding and a concomitant
      conformational change in subdomain A, with the double mutant displaying
      significant defects in helicase activity as well. We propose a model in which MCM
      loading and the subsequent activation of the helicase activity involve a
      conformational transition that is connected to a DNA binding event.

PMID- 19116206
TI  - Confocal laser Raman microspectroscopy of biomineralization foci in UMR 106
      osteoblastic cultures reveals temporally synchronized protein changes preceding
      and accompanying mineral crystal deposition.
AB  - Mineralization in UMR 106-01 osteoblastic cultures occurs within extracellular
      biomineralization foci (BMF) within 12 h after addition of beta-glycerol
      phosphate to cells at 64 h after plating. BMF are identified by their enrichment
      with an 85-kDa glycoprotein reactive with Maackia amurensis lectin. Laser Raman
      microspectroscopic scans were made on individual BMF at times preceding (64-76 h)
      and following the appearance of mineral crystals (76-88 h). The range of
      variation between spectra for different BMF in the same culture was rather small.
      In contrast, significant differences were observed for spectral bands at 957-960,
      1004, and 1660 cm(-1) when normalized BMF spectra at different times were
      compared. Protein-dependent spectral bands at 1004 and 1660 cm(-1) increased and
      then decreased preceding the detection of hydroxyapatite crystals via the
      phosphate stretching peak at 959-960 cm(-1). When sodium phosphate was
      substituted for beta-glycerol phosphate, mineralization occurred 3-6 h earlier.
      Irrespective of phosphate source, the Raman full peak width at half-maximum ratio
      for 88 h cultures was similar to that for 10-day-old marrow ablation primary
      bone. However, if mineralization was blocked with serine protease inhibitor 4-(2
      aminoethyl)benzenesulfonyl fluoride hydrochloride, 64-88-h BMF spectra remained
      largely invariant. In summary, Raman spectral data demonstrate for the first time
      that formation of hydroxyapatite crystals within individual BMF is a multistep
      process. Second, changes in protein-derived signals at 1004 and 1660 cm(-1)
      reflect events within BMFs that precede or accompany mineral crystal production
      because they are blocked by mineralization inhibitor 4-(2
      aminoethyl)benzenesulfonyl fluoride hydrochloride. Finally, the low extent of
      spectral variability detected among different BMF at the same time point
      indicates that mineralization of individual BMF within a culture is synchronized.

PMID- 19116207
TI  - Functional ryanodine receptors in the plasma membrane of RINm5F pancreatic beta
      cells.
AB  - Ryanodine receptors (RyR) are Ca(2+) channels that mediate Ca(2+) release from
      intracellular stores in response to diverse intracellular signals. In RINm5F
      insulinoma cells, caffeine, and 4-chloro-m-cresol (4CmC), agonists of RyR,
      stimulated Ca(2+) entry that was independent of store-operated Ca(2+) entry, and
      blocked by prior incubation with a concentration of ryanodine that inactivates
      RyR. Patch-clamp recording identified small numbers of large-conductance
      (gamma(K) = 169 pS) cation channels that were activated by caffeine, 4CmC or low
      concentrations of ryanodine. Similar channels were detected in rat pancreatic
      beta-cells. In RINm5F cells, the channels were blocked by cytosolic, but not
      extracellular, ruthenium red. Subcellular fractionation showed that type 3 IP(3)
      receptors (IP(3)R3) were expressed predominantly in endoplasmic reticulum,
      whereas RyR2 were present also in plasma membrane fractions. Using RNAi
      selectively to reduce expression of RyR1, RyR2, or IP(3)R3, we showed that RyR2
      mediates both the Ca(2+) entry and the plasma membrane currents evoked by
      agonists of RyR. We conclude that small numbers of RyR2 are selectively expressed
      in the plasma membrane of RINm5F pancreatic beta-cells, where they mediate Ca(2+)
      entry.

PMID- 19116208
TI  - An alternative form of replication protein a prevents viral replication in vitro.
AB  - Replication protein A (RPA), the eukaryotic single-stranded DNA-binding complex,
      is essential for multiple processes in cellular DNA metabolism. The "canonical"
      RPA is composed of three subunits (RPA1, RPA2, and RPA3); however, there is a
      human homolog to the RPA2 subunit, called RPA4, that can substitute for RPA2 in
      complex formation. We demonstrate that the resulting "alternative" RPA (aRPA)
      complex has solution and DNA binding properties indistinguishable from the
      canonical RPA complex; however, aRPA is unable to support DNA replication and
      inhibits canonical RPA function. Two regions of RPA4, the putative L34 loop and
      the C terminus, are responsible for inhibiting SV40 DNA replication. Given that
      aRPA inhibits canonical RPA function in vitro and is found in nonproliferative
      tissues, these studies indicate that RPA4 expression may prevent cellular
      proliferation via replication inhibition while playing a role in maintaining the
      viability of quiescent cells.

PMID- 19116210
TI  - Elastase digests: new ammunition for shotgun membrane proteomics.
AB  - Despite many advances in membrane proteomics during the last decade the
      fundamental problem of accessing the transmembrane regions itself has only been
      addressed to some extent. The present study establishes a method for the nano-LC
      based analysis of complex membrane proteomes on the basis of a methanolic porcine
      pancreatic elastase digest to increase transmembrane coverage. Halobacterium
      salinarium purple and Corynebacterium glutamicum membranes were successfully
      analyzed by using the new protocol. We demonstrated that elastase digests yield a
      large proportion of transmembrane peptides, facilitating membrane protein
      identification. The potential for characterization of a membrane protein through
      full sequence coverage using elastase is there but is restricted to the higher
      abundance protein components. Compatibility of the work flow with the two most
      common mass spectrometric ionization techniques, ESI and MALDI, was shown.
      Currently better results are obtained using ESI mainly because of the low
      response of MALDI for strictly neutral peptides. New findings concerning elastase
      specificity in complex protein mixtures reveal a new prospect beyond the
      application in shotgun experiments. Furthermore peptide mass fingerprinting with
      less specific enzymes might be done in the near future but requires an adaptation
      of current search algorithms to the new proteases.

PMID- 19116211
TI  - Serum adiponectin levels in patients with esophageal cancer.
AB  - OBJECTIVE: The aim of the study was to investigate a possible relationship
      between serum levels of adiponectin and clinicopathological characteristics in
      esophageal cancer. This is the first report evaluating serum adiponectin levels
      in patients with esophageal cancer. METHODS: Sixty-two patients with esophageal
      cancer and thirty healthy subjects were included in the study. Adiponectin levels
      were determined by an enzyme-linked immunosorbent assay kit. RESULTS: The mean
      serum adiponectin level in the cancer group was significantly low compared with
      the adiponectin level in the healthy control group. Furthermore, adiponectin
      levels of the patients gradually decreased with increase in tumor stage. The
      patients with adenocarcinoma of the esophagus had significantly lower values of
      serum adiponectin than patients with squamous cell carcinoma. CONCLUSION: We
      concluded that decreased circulating adiponectin levels may play a role in the
      progression and/or development of esophageal cancers. However, for clinical use
      of serum adiponectin in terms of early diagnosis and treatment, further studies
      should be performed.

PMID- 19116209
TI  - MMP-9 sheds the beta2 integrin subunit (CD18) from macrophages.
AB  - Activated macrophages are essential effectors of immunity and a rich source of
      matrix metalloproteinase-9 (MMP-9; gelatinase B). To search for cellular
      substrates of the enzyme, we subjected wild-type macrophages and macrophages
      expressing an autoactivating form of pro-MMP-9 (M9A macrophages) to proteomics
      analysis. Two-dimensional liquid chromatography together with tandem mass
      spectrometry identified 467 proteins in medium conditioned by M9A and/or wild
      type macrophages. Subtractive proteomics identified 18 candidate MMP-9
      substrates. Biochemical studies confirmed that two transmembrane proteins,
      beta(2) integrin subunit (CD18) and amyloid protein precursor (APP), were
      enriched in the medium of M9A macrophages. To identify potential cleavage sites,
      we synthesized an overlapping library of peptides that spanned 60 residues of the
      ectodomain and transmembrane domain of beta(2) integrin. Active MMP-9 cleaved a
      single peptide, ECVKGPNVAAIVGGT, at residues corresponding to Ala(705) and
      Ile(706) of the beta(2) integrin. Peptides corresponding to this cleavage site
      were detected by tandem mass spectrometric analysis only in medium from M9A
      macrophages, strongly supporting the proposal that beta(2) integrin is shed by
      autoactivating MMP-9. Our observations indicate that subtractive proteomics in
      concert with peptide substrate mapping is a powerful approach for identifying
      proteolytic substrates and suggest that MMP-9 plays previously unsuspected roles
      in the regulation and shedding of beta(2) integrin.

PMID- 19116212
TI  - Adjuvant radiotherapy for breast cancer.

PMID- 19116213
TI  - Electroconvulsive therapy.

PMID- 19116214
TI  - Antibiotics for spontaneous preterm birth.

PMID- 19116215
TI  - Virginity pledge ineffective against teen sex despite government funding, US
      study finds.

PMID- 19116216
TI  - Hospitals in Gaza struggle to cope with large influx of wounded patients.

PMID- 19116217
TI  - Nutrition and the prevention and treatment of cancer: association of cytochrome
      P450 CYP1B1 with the role of fruit and fruit extracts.
AB  - Recommendations for a healthy or prudent diet include a large number of daily
      servings of fruits and vegetables, and these 2 classes of food are widely
      believed to assist in cancer prevention. One potential mechanism that is rarely
      mentioned in nutritional studies involves the cytochrome P450 enzyme CYP1B1,
      which appears to have the unique properties of being a universal cancer marker
      overexpressed in cancer cells and having the capability of converting various
      phytochemicals and synthetic chemicals into substances cytotoxic to these cells.
      Although these particular features of CYP1B1 have not gone unnoticed, there has
      been relatively little research aimed at exploiting them. Furthermore,
      therapeutic and preventive strategies currently being considered based on
      vaccines against the enzyme or inhibition without the generation of cytotoxins
      can be questioned because they do not take advantage of the unique properties of
      this enzyme. In addition, a few relevant case histories have been published that
      use specially designed fruit extracts containing substrates with demonstrated
      cytotoxic metabolic products, and these reports provide an initial confirmation
      of the potential of exploiting the unusual properties of this enzyme for cancer
      therapy.

PMID- 19116218
TI  - Enzymes and cancer: a look toward the past as we move forward.

PMID- 19116219
TI  - Introduction to the John Beard special issue.

PMID- 19116220
TI  - The life and times of John Beard, DSc (1858-1924).
AB  - The British developmental biologist John Beard, DSc (1858-1924) is little
      remembered today. Yet, he made outstanding contributions to the life sciences.
      Beard deserves to be included among the leading biologists of the late 19th and
      early 20th century. He has been hailed as a forerunner of the present-day theory
      of the cancer stem cell (CSC). He was the first to point to the parallels between
      cancer and the trophoblastic cells that envelop and nourish the embryo,
      characterizing cancer as "irresponsible trophoblast." He pointed out that the
      initiation of fetal pancreatic function coincided with a reduction in the
      invasiveness of trophoblast, which otherwise might progress to clinical cancer
      (ie, choriocarcinoma). Based on the above propositions, he recommended the
      therapeutic use of pancreatic enzymes in treating cancer and other diseases. This
      therapy created a worldwide controversy, and although rejected in his day,
      persists in the world of complementary and alternative medicine (CAM) today.

PMID- 19116221
TI  - John Beard timeline.

PMID- 19116222
TI  - Enzymes, trophoblasts, and cancer: the afterlife of an idea (1924-2008).
AB  - In the early 20th century, advocacy of the enzyme therapy of cancer was primarily
      the work of one man, John Beard, DSc (1858-1924). He and his collaborators made a
      determined effort to establish this mode of therapy, especially in the years 1905
      to 1911. Despite a brief flowering of international interest, Beard's efforts
      came to naught. During the 20th century, there was a succession of American
      researchers who continued to investigate this topic. This included Marshall
      William McDuffie, MD (1882-1945), Frank LeForest Morse, MD (1876-1953), Franklin
      Lloyd Shively, MD (1887-1971), and William Donald Kelley (1926-2005). In central
      Europe, India, and other parts of the globe, the use of pancreatic enzymes as an
      adjuvant treatment for cancer has become a fairly routine practice, at least
      among those doctors who utilize complementary and alternative medicine (CAM). It
      is also a well-established method for reducing inflammation and mitigating the
      adverse effects of cytotoxic treatment.

PMID- 19116223
TI  - Of germ cells, trophoblasts, and cancer stem cells.
AB  - The trophoblastic theory of cancer, proposed in the early 1900s by Dr John Beard,
      may not initially seem relevant to current cancer models and treatments. However,
      the underpinnings of this theory are remarkably similar to those of the cancer
      stem cell (CSC) theory. Beard noticed that a significant fraction of germ cells
      never reach their final destination as they migrate during embryonic development
      from the hindgut to the germinal ridge. In certain situations, upon aberrant
      stimulation, these vagrant germ cells are able to generate tumors.
      Simplistically, the CSC theory surmises that a small population of tumorigenic
      cells exists, which initiate and maintain tumors, and these cells have a likely
      origin in normal stem cells. Both these theories are based on the potential of a
      single primitive cell to form a tumor. This has a major implication for cancer
      therapy, in that only a small percentage of cells need to be targeted to ablate a
      tumor.

PMID- 19116224
TI  - Differential effects of serine proteases on the migration of normal and tumor
      cells: implications for tumor microenvironment.
AB  - The supporting role of proteases in tumor progression and invasion is well known;
      however, the use of proteases as therapeutic agents has also been demonstrated.
      In this article, the authors report on the differential effects of exogenous
      serine proteases on the motility of tumor and normal cells. The treatment of
      normal and tumor cells with a single dose of pancreatic serine proteases, trypsin
      (TR) and chymotrypsin (CH), leads to a concentration-dependent response by cells,
      first accelerating and then slowing mobility. Tumor cells are 10 to 20 times more
      sensitive to exogenous TR/CH, suggesting that a single dose of proteases may
      cause discordant movements of normal and tumor cells within the tumor
      environment. The inhibitory effects of TR on cell motility are contradicted by
      thrombin (TH), particularly in the regulation of normal cells' migration. The
      purpose of this investigation was to ascertain the role of protease-activated
      receptors (PARs) in terms of normal and tumor cell motility. Duplicate treatments
      with proteases resulted in diminished mobility of both normal and tumor cells.
      Repeated application of TR and TH in 1-hour treatment intervals initially
      desensitizes cell surface PARs. However, cell surface PARs reappear regardless of
      subsequent protease treatments in both normal and tumor cells. The
      resensitization process is retarded in tumor cells when compared with normal
      cells. This is evidenced by lower expression of PARs as well as by their
      relocalization at the tumor cell surfaces. Under these conditions, normal cells
      remain responsive to exogenous proteases in terms of cell motility. Exogenous
      proteases do not modulate motility of repeatedly stimulated tumor cells, and
      consequently, the migration of tumor cells appears disconnected from the PAR
      signaling pathways. The use of activating peptides in lieu of the cognate
      proteases for a given PAR system indicated that proteases may act through
      additional targets not regulated by PAR signaling. We hypothesize that the
      divergent migration patterns of normal and tumor cells due to exposure to
      proteases is in part mediated by PARs. Thus, treatment with exogenous proteases
      may cause rearrangement of the tumor and stromal cells within the tumor
      microenvironment. Such topographical effects may lead to the inhibition of tumor
      progression and metastasis development.

PMID- 19116225
TI  - Exogenous proteases confer a significant chemopreventive effect in experimental
      tumor models.
AB  - In this monograph, the chemopreventive effects of enterally administered
      proteases (trypsin, chymotrypsin, and papain) have been documented in a series of
      animal experimental tumor models. The experimental evidence demonstrates a
      significant inhibition of growth of both the primary tumor and the metastatic
      disseminations. Survival in animals treated with proteases is significantly
      longer than in untreated animals. The results confirm the fundamental correlation
      between early initiation of therapy and consequent growth of the tumorous
      disease. Comparable results have been shown in solid tumors in animal models
      (melanoma and Lewis lung carcinoma) and in human tumors (pancreatic and breast
      cancers). In this article, details of the known mechanisms of systemic actions of
      enterally administered proteases are documented and their relationship with
      cancerogenesis is discussed.

PMID- 19116226
TI  - Proteolytic enzyme therapy in evidence-based complementary oncology: fact or
      fiction?
AB  - Systemic enzyme therapy was recently subjected to experimental investigations and
      to rigorous clinical studies in cancer patients. The designs of the relevant
      clinical cohort studies followed the guidelines of Good Epidemiological Practice
      and represent level IIB in evidence-based medicine (EBM). Scientifically sound
      experimental in vitro and in vivo investigations are far advanced and document
      promising immunological, anti-inflammatory, anti-infectious, and
      antitumor/antimetastatic activities of proteolytic enzyme mixtures (containing
      trypsin, chymotrypsin, and papain) or bromelain. EBM level II clinical studies,
      which are accepted by the European Union to show safety and efficacy of medical
      treatments, were performed to evaluate the benefit of complementary systemic
      enzyme therapy in cancer patients suffering from breast and colorectal cancers
      and plasmacytoma. These studies demonstrated that systemic enzyme therapy
      significantly decreased tumor-induced and therapy-induced side effects and
      complaints such as nausea, gastrointestinal complaints, fatigue, weight loss, and
      restlessness and obviously stabilized the quality of life. For plasmacytoma
      patients, complementary systemic enzyme therapy was shown to increase the
      response rates, the duration of remissions, and the overall survival times. These
      promising data resulted in an "orphan drug status" designation for a systemic
      enzyme product, which should motivate further studies on this complementary
      treatment.

PMID- 19116227
TI  - An annotated bibliography of works by John Beard.
AB  - This article provides a bibliography of the scientific publications of John
      Beard, DSc (1858-1924). Beard was an English embryologist and cancer researcher
      of the late 19th and early 20th century, who devised the trophoblastic theory of
      cancer, a forerunner of today's theory of cancer stem cells. Beard was the author
      of more than 100 scientific articles and monographs, as well as the book The
      Enzyme Treatment of Cancer (1911). This is the first bibliography ever compiled
      of his scientific publications.

PMID- 19116228
TI  - Tricks of the trade in community mental health research: working with mental
      health services and clients.
AB  - The complexities of research in the community mental health sector are seldom
      acknowledged in existing literature; this article attempts to address this void.
      It presents the methodological challenges experienced in the longitudinal
      evaluation of the Housing and Accommodation Support Initiative-a program that
      supports people with chronic mental illness toward long-term recovery. The
      evaluation provides a case study for understanding methodological problems in
      community mental health research, which include working with organizations that
      experience high staff turnover; staff members who have large caseloads; and
      clients who have chronic mental illness. Although not applicable to all research
      designs, the suggested strategies highlight the importance of innovation,
      flexibility, and balance between research theory and practical limitations when
      conducting community mental health research.

PMID- 19116229
TI  - Community health program evaluation using accreditation as a framework.
AB  - Increasingly, health system leaders seek to determine whether community health
      interventions make a difference to individuals in the community. However,
      community health improvement is difficult to measure, and health system staff may
      not be familiar with evaluation research methods. Health care organizations can
      improve their evaluation efforts relatively easily by building on what they
      already know: the Joint Commission accreditation process. By using accreditation
      as a framework, community health evaluation may be seen as more approachable when
      viewed through that lens. This article provides a framework for practical
      approaches to program planning, evaluation, and sustainability. Joint Commission
      accreditation functions (chapters) are similar to health program goals. Standards
      are similar to program objectives. Elements of performance are similar to
      activities or methods. Scoring comparisons are similar to measures.

PMID- 19116230
TI  - Unilateral jugular vein phlebectasia.

PMID- 19116231
TI  - Influence of Slc11a1 (formerly Nramp1) on DSS-induced colitis in mice.
AB  - Multiple genetic studies in humans indicate a role for solute carrier family 11a
      member 1 [SLC11A1; formerly natural resistance-associated macrophage protein 1
      (NRAMP1)] in autoimmune disease susceptibility, including ulcerative colitis.
      Murine Slc11a1 has many pleiotropic effects on macrophage activation and
      proinflammatory responses. To determine which of these are important in
      ulcerative colitis, we established a phenotype for oral dextran sulfate sodium
      (DSS)-induced acute colitis in congenic Slc11a1 wild-type (wt) and mutant (mt)
      mice on a B10 background. For over 7 days of treatment with 2% DSS in the
      drinking water, Slc11a1 wt mice showed enhanced acute ulcerative colitis, as
      demonstrated by significantly greater body weight loss and reduction in colon
      length, as well as a marked increase in monocyte/macrophage inflammatory
      infiltrates and histopathology changes in the colon. This was accompanied by a
      clear, inverse relationship between IFN-gamma and IL-10 responses in Slc11a1 wt
      compared with mt mice, resulting in a significantly higher ratio of IFN-gamma:IL
      10 in wt compared with mt mice in lymph node and splenic T cells. RNase
      protection assays confirmed the presence of significantly higher IFN-gamma at the
      RNA level in the colons of wt compared with mt mice at Day 7 of treatment.
      Interestingly this was accompanied by significantly enhanced RNA levels for the
      acute-phase protein IL-6, which is known to inhibit the generation of forkhead
      box P3+ regulatory T cells and help to drive the differentiation of Th17 from
      naive T cells and not by differences in RNA for IL-12p35 or IL-12p40 molecules
      that dimerize to form the Th1-inducing cytokine IL-12.

PMID- 19116232
TI  - Estimated maternal ultraviolet B exposure levels in pregnancy influence skeletal
      development of the child.
AB  - CONTEXT: Relationships between vitamin D exposure of the mother in pregnancy and
      skeletal development of the child are poorly understood. OBJECTIVES: Our
      objectives were to establish whether background UVB levels in the third trimester
      of pregnancy are related to bone mineral content (BMC) of the child, and to
      examine whether these relationships are explained by effects on height, fat, or
      lean mass. DESIGN: This was a prospective cohort study. SETTING: The Avon
      Longitudinal Study of Parents and Children, a population-based birth cohort, was
      studied. PARTICIPANTS: A total of 6995 boys and girls with a mean age of 9.9 yr
      was studied. OUTCOME MEASURES: Prespecified analyses of relationships between
      background UVB levels in the third trimester of pregnancy, and total body less
      head BMC, bone area (BA), bone mineral density, and area-adjusted BMC as measured
      by dual-energy x-ray absorptiometry scans at 9.9 yr were performed. RESULTS:
      Maternal UVB exposure was positively related to BMC (g) [9.6 (5.3, 13.8)], BA
      (cm(2)) [8.1 (4.3, 11.9)], and bone mineral density (g/cm(-2)) [0.003 (0.001,
      0.004)], but not area-adjusted BMC (g) [0.69 (-0.22, 1.56)], suggesting an effect
      on bone size. Both height-dependent (cm) [0.18 (0.03, 0.32)] and height
      independent (cm(2)) [4.1, (2.0, 6.2)] effects contributed to this association
      between UVB and BA. Although maternal UVB exposure was also related to lean mass
      (g) [163 (89, 237)], a positive association between UVB and BA persisted after
      adjusting for both height and lean mass [2.8 (1.0, 4.6)]. CONCLUSIONS: Maternal
      UVB exposure is related to bone size at age 9.9 yr independently of height and
      lean mass, suggesting that vitamin D status in pregnancy exerts direct effects on
      periosteal bone formation in subsequent childhood.

PMID- 19116233
TI  - Serum half-life of pituitary gonadotropins is decreased by sulfonation and
      increased by sialylation in women.
AB  - CONTEXT: The gonadotropins are secreted from the human pituitary as spectra of
      isoforms with different degrees of sulfonation and sialylation of the
      oligosaccharides, modifications suspected to determine their half-lives in the
      circulation. OBJECTIVES: Our objectives were to determine the isoform composition
      of the serum gonadotropins during GnRH receptor blockade, and to estimate the
      half-lives in circulation of isoforms with 0-1-2-3 sulfonated N
      acetylgalactosamine (SO(3)-GalNAc) residues. DESIGN/PARTICIPANTS: Serum samples
      were collected in seven healthy women before and up to 20 h after administration
      of the NAL-GLU GnRH antagonist. MAIN OUTCOME MEASURES: The number of sialic acid
      and SO(3)-GalNAc residues per LH and FSH molecule and the distribution of
      molecules with 0-1-2-3 sulfonated residues were measured. The half-lives were
      estimated by monoexponential decay. RESULTS: More sialylated and less sulfonated
      gonadotropin isoforms remain longer in circulation during GnRH receptor blockade.
      LH isoforms with two and three sulfonated residues per molecule had shorter half
      lives compared with those with zero and one (109 and 80 vs. 196 and 188 min; P <
      0.01). FSH isoforms with one and two sulfonated residues had shorter half-lives
      than those with zero (485 and 358 vs. 988 min; P < 0.01). CONCLUSIONS: The
      decline in LH and FSH during GnRH receptor blockade is associated with a decrease
      in sulfonated and increase in sialylated residues. The rapid disappearance of LH
      isoforms with two and three SO(3)-GalNAc residues suggests their removal by
      hepatic SO(3)-GalNAc-receptors similar to those in rodents. Episodical secretion
      of spectra of isoforms with different half-lives is expected to lead to
      continuous changes in gonadotropin isoform compositions in blood.

PMID- 19116234
TI  - Prophylactic lymph node dissection for papillary thyroid cancer less than 2 cm:
      implications for radioiodine treatment.
AB  - OBJECTIVE: Prophylactic neck dissection for small papillary carcinoma remains
      controversial. Radioiodine ablation is not recommended for tumors less than 10 mm
      and depends on various factors for tumors between 10 and 20 mm. The aim was to
      determine the effect of lymph node (LN) staging on the indication for treatment
      with radioiodine. PATIENTS AND METHODS: We conducted a retrospective study of 115
      patients presenting with papillary thyroid carcinoma less than 2 cm without
      ultrasonographically detectable cervical LN treated by total thyroidectomy and
      complete selective dissection of the central and lateral compartment. Radioiodine
      treatment was based on definitive pathology (tumor and LN). Follow-up was based
      on neck ultrasound and thyroglobulin levels. RESULTS: LN were found for 41.7% of
      cases. Radioiodine was not used for 42% of patients with tumors less than 20 mm
      and no metastatic LN. Fifty-eight percent of patients were treated with
      radioiodine due to LN metastasis, extracapsular thyroid invasion, or unfavorable
      histological subtype. LN status affected the indication for radioiodine in 30.5%
      of cases classified as T1, 12 cases with tumors less than 10 mm but with LN
      metastases (who received radioiodine), and 13 cases with tumors between 10 and 20
      mm but without LN metastases (who did not receive radioiodine). Definitive vocal
      fold paralysis and hypoparathyroidism each occurred in 0.9% of cases. At 1 yr,
      ultrasound was normal in all patients, and recombinant human TSH-stimulated
      thyroglobulin was undetectable for 97% of the patients. CONCLUSION: Precise LN
      staging by prophylactic neck dissection for tumors initially staged T1N0 modified
      the indication for radioiodine ablation for 30% of patients.

PMID- 19116235
TI  - Risk factors associated with a low glomerular filtration rate in primary
      aldosteronism.
AB  - CONTEXT: Primary aldosteronism (PA) is associated with vascular end organ damage.
      OBJECTIVE: We evaluated the newly established German Conn's Registry for evidence
      of renal impairment and compared the data with those from hypertensive subjects
      of a population-based survey. DESIGN: We conducted a case-control study. PATIENTS
      AND CONTROLS: A total of 408 patients with PA from the Conn's registry treated in
      five German centers were matched for age, sex, and body mass index in a 1:1 ratio
      with 408 hypertensive control subjects from the population-based F3 survey of the
      Kooperative Gesundheitsforschung in the region of Augsburg (KORA). MAIN OUTCOME
      MEASURES: We measured serum creatinine and calculated glomerular filtration rate
      (GFR). RESULTS: The percentage of patients with a serum creatinine concentration
      above the normal range of 1.25 mg/dl was higher in patients with PA than in
      hypertensive controls (29 vs. 10%; P < 0.001). Regression analysis showed that
      age, male sex, low potassium, and high aldosterone concentrations were
      independent predictors of a lower GFR. Adrenalectomy reduced systolic blood
      pressure from a mean of 160 to 144 mm Hg. In parallel, we observed an increase in
      serum creatinine and a decrease of GFR from 71 to 64 ml/min (P < 0.001). A
      similar trend was seen after spironolactone treatment. CONCLUSIONS: In a large
      cohort of patients with PA, markers of disease activity such as plasma
      aldosterone and serum potassium are independent predictors of a lower GFR.
      Specific interventions, such as adrenalectomy or spironolactone treatment, are
      associated with a further decline in GFR.

PMID- 19116236
TI  - A novel CYP11B2 gene mutation in an Asian family with aldosterone synthase
      deficiency.
AB  - CONTEXT: Three siblings of Pakistani origin presented neonatally with isolated
      hyperreninemic hypoaldosteronism and were well controlled on fludrocortisone
      therapy during childhood and adolescence. OBJECTIVE/DESIGN: These individuals
      were reevaluated as adults after fludrocortisone withdrawal to investigate the
      biochemical and molecular basis of their disorder. RESULTS: When reassessed off
      fludrocortisone treatment, hyperreninemic hypoaldosteronism was confirmed in all
      subjects but with significant hyperkalemia in only one case. Profiling of urinary
      steroid metabolites showed a biochemical pattern (elevated
      tetrahydrocorticosterone to 18-hydroxytetrahydro-11-dehydrocorticosterone ratio
      but normal 18-hydroxytetrahydro-11-dehydrocorticosterone to tetrahydroaldosterone
      ratio) consistent with partial type 1 aldosterone synthase deficiency. Sequencing
      of the CYP11B2 gene showed that affected subjects were homozygous for a single
      nucleotide substitution (T925C) in exon 5, corresponding to a serine to proline
      mutation (S308P) in the predicted protein, with unaffected family members being
      heterozygous. Consistent with structural modeling showing that the mutated
      residue is located within the alpha-helix I, close to the hemebinding, active
      site of the enzyme, functional characterization of the S308P mutant protein in
      vitro showed complete loss of enzyme activity. However, administration of
      dexamethasone further reduced levels of circulating aldosterone and its urinary
      metabolites in affected subjects, suggesting that some mineralocorticoid
      biosynthesis occurs in vivo. CONCLUSION: We have identified the first CYP11B2
      gene defect in a family of Asian origin, associated with a type 1 aldosterone
      synthase deficiency phenotype. Preservation of some aldosterone production
      suggests either residual mutant CYP11B2 enzyme activity in vivo or
      mineralocorticoid biosynthesis via an alternative pathway.

PMID- 19116237
TI  - Very low density lipoprotein metabolism and plasma adiponectin as predictors of
      high-density lipoprotein apolipoprotein A-I kinetics in obese and nonobese men.
AB  - CONTEXT: Hypercatabolism of high-density lipoprotein (HDL) apolipoprotein (apo) A
      I results in low plasma apoA-I concentration. The mechanisms regulating apoA-I
      catabolism may relate to alterations in very low density lipoprotein (VLDL)
      metabolism and plasma adiponectin and serum amyloid A protein (SAA)
      concentrations. OBJECTIVE: We examined the associations between the fractional
      catabolic rate (FCR) of HDL-apoA-I and VLDL kinetics, plasma adiponectin, and SAA
      concentrations. STUDY DESIGN: The kinetics of HDL-apoA-I and VLDL-apoB were
      measured in 50 obese and 37 nonobese men using stable isotopic techniques.
      RESULTS: In the obese group, HDL-apoA-I FCR was positively correlated with
      insulin, homeostasis model of assessment for insulin resistance (HOMA-IR) score,
      triglycerides, VLDL-apoB, and VLDL-apoB production rate (PR). In the nonobese
      group, HDL-apoA-I FCR was positively correlated with triglycerides, apoC-III,
      VLDL-apoB, and VLDL-apoB PR and negatively correlated with plasma adiponectin.
      Plasma SAA was not associated with HDL-apoA-I FCR in either group. In multiple
      regression analyses, VLDL-apoB PR and HOMA-IR score, and VLDL-apoB PR and
      adiponectin were independently predictive of HDL-apoA-I FCR in the obese and
      nonobese groups, respectively. HDL-apoA-I FCR was positively and strongly
      associated with HDL-apoA-I PR in both groups. CONCLUSIONS: Variation in VLDL-apoB
      production, and hence plasma triglyceride concentrations, exerts a major effect
      on the catabolism of HDL-apoA-I. Insulin resistance and adiponectin may also
      contribute to the variation in HDL-apoA-I catabolism in obese and nonobese
      subjects, respectively. We also hypothesize that apoA-I PR determines a steady
      state, lowered plasma of apoA-I, which may reflect a compensatory response to a
      primary defect in the catabolism of HDL-apoA-I due to altered VLDL metabolism.

PMID- 19116239
TI  - Study of circulating prohepcidin in association with insulin sensitivity and
      changing iron stores.
AB  - BACKGROUND: Liver synthesizes hepcidin in response to iron overload, leading to
      down-regulation of duodenal iron absorption. The pathophysiology of type 2
      diabetes is associated with increased iron stores. We aimed to study circulating
      prohepcidin in association with insulin sensitivity and parameters of glucose and
      iron metabolism. METHODS: Serum prohepcidin was evaluated in three cohorts: 1) a
      cross-sectional study (cohort 1, men from the general population; n = 135); 2)
      after decreasing iron stores in men with "high-ferritin" type 2 diabetes (cohort
      2; n = 13); and 3) after decreasing iron stores in men carrying HFE gene
      mutations (cohort 3; n = 16). Insulin sensitivity was measured using either the
      minimal model or the clamp technique. RESULTS: Circulating prohepcidin correlated
      significantly with glycated hemoglobin (P < 0.0001), fasting glucose (P = 0.002),
      triglycerides (P = 0.007), high-density lipoprotein-cholesterol (P = 0.01),
      ferritin (P = 0.01), and soluble transferrin receptor concentration (P = 0.001)
      in subjects from cohort 1. Prohepcidin decreased significantly after iron
      depletion in patients with type 2 diabetes (P = 0.04) (cohort 2) and in carriers
      of HFE gene mutations (P = 0.03) (cohort 3). In the latter subjects, the change
      in serum prohepcidin after iron depletion was associated with the change in both
      fasting glucose transferrin (r = 0.58; P = 0.02) and saturation (r = 0.68; P =
      0.005). The changes in insulin sensitivity were associated with those of liver
      iron content (r = -0.64; P = 0.007) and with those of serum prohepcidin (r = 
      0.50; P = 0.04) (cohort 3). CONCLUSIONS: These associations suggest that
      circulating prohepcidin concentration is pathophysiologically associated with
      parameters of glucose and iron metabolism. A failure to increase prohepcidin
      synthesis is hypothesized to contribute to iron-induced disorders of glucose
      metabolism.

PMID- 19116238
TI  - Genetic variations in sex steroid-related genes as predictors of serum estrogen
      levels in men.
AB  - CONTEXT: The risk of many conditions, including prostate cancer, breast cancer,
      and osteoporosis, is associated with serum levels of sex steroids. OBJECTIVE: The
      aim of the study was to identify genetic variations in sex steroid-related genes
      that are associated with serum levels of estradiol (E2) and/or testosterone in
      men. DESIGN: Genotyping of 604 single nucleotide polymorphisms in 50 sex steroid
      related candidate genes was performed in the Gothenburg Osteoporosis and Obesity
      Determinants (GOOD) study (n = 1041 men; age, 18.9 +/- 0.6 yr). Replications of
      significant associations were performed in the Osteoporotic Fractures in Men
      (MrOS) Sweden study (n = 2568 men; age, 75.5 +/- 3.2 yr) and in the MrOS US study
      (n = 1922 men; age, 73.5 +/- 5.8 yr). Serum E2, testosterone, and estrone (E1)
      levels were analyzed using gas chromatography/mass spectrometry. RESULTS: The
      screening in the GOOD cohort identified the single nucleotide polymorphism
      rs2470152 in intron 1 of the CYP19 gene, which codes for aromatase, responsible
      for the final step of the biosynthesis of E2 and E1, to be most significantly
      associated with serum E2 levels (P = 2 x 10(-6)). This association was confirmed
      both in the MrOS Sweden study (P = 9 x 10(-7)) and in the MrOS US study (P = 1 x
      10(-4)). When analyzed in all subjects (n = 5531), rs2470152 was clearly
      associated with both E2 (P = 2 x 10(-14)) and E1 (P = 8 x 10(-19)) levels. In
      addition, this polymorphism was modestly associated with lumbar spine BMD (P <
      0.01) and prevalent self-reported fractures (P < 0.05). CONCLUSIONS: rs2470152 of
      the CYP19 gene is clearly associated with serum E2 and E1 levels in men.

PMID- 19116240
TI  - A novel homozygous mutation in CYP11A1 gene is associated with late-onset adrenal
      insufficiency and hypospadias in a 46,XY patient.
AB  - CONTEXT: The first and the rate-limiting step in the biosynthesis of hormones in
      all steroidogenic tissues, conversion of cholesterol to pregnenolone, is
      catalyzed by the cholesterol side-change cleavage cytochrome P450 (P450scc)
      encoded by a single gene, CYP11A1. To date, mutations in CYP11A1 gene have been
      reported in six patients, all of whom presented with adrenal insufficiency within
      the first 4 yr of life and severely underandrogenized external genitalia (Prader
      stages 1-2). OBJECTIVE: Our aim was to characterize in vitro and in vivo effects
      of a novel homozygous CYP11A1 gene mutation identified in a patient with an
      unusual presentation of P450scc deficiency. METHODS AND PATIENTS: A 46,XY patient
      presented with mid-shaft hypospadias and cryptorchidism at birth and signs of
      adrenal failure at 9 yr. Mutational analysis of CYP11A1 gene was performed by
      PCR, followed by direct sequencing. P450scc activity was determined by measuring
      concentration of pregnenolone synthesized from cholesterol in the medium after a
      transient transfection of HEK293 cells with P450scc, adrenodoxin, adrenodoxin
      reductase, and steroidogenic acute regulatory protein expression plasmids.
      RESULTS: The sequencing of CYP11A1 gene in the proband revealed a novel
      homozygous L222P mutation, whereas both parents were heterozygous carriers for
      this mutation. In vitro P450scc activity of L222P mutant was approximately 7%
      compared with the wild type. CONCLUSIONS: This case represents the mildest
      phenotype of P450scc deficiency to be described. The phenotypic presentation was
      consistent with the partial reduction of P450scc activity of L222P mutant.

PMID- 19116241
TI  - Electrotonic vascular signal conduction and nephron synchronization.
AB  - Tubuloglomerular feedback (TGF) and the myogenic mechanism control afferent
      arteriolar diameter in each nephron and regulate blood flow. Both mechanisms
      generate self-sustained oscillations, the oscillations interact, TGF modulates
      the frequency and amplitude of the myogenic oscillation, and the oscillations
      synchronize; a 5:1 frequency ratio is the most frequent. TGF oscillations
      synchronize in nephron pairs supplied from a common cortical radial artery, as do
      myogenic oscillations. We propose that electrotonic vascular signal propagation
      from one juxtaglomerular apparatus interacts with similar signals from other
      nephrons to produce synchronization. We tested this idea in tubular-vascular
      preparations from mice. Vascular smooth muscle cells were loaded with a
      fluorescent voltage-sensitive dye; fluorescence intensity was measured with
      confocal microscopy. Perfusion of the thick ascending limb activated TGF and
      depolarized afferent arteriolar smooth muscle cells. The depolarization spread to
      the cortical radial artery and other afferent arterioles and declined with
      distance from the perfused juxtaglomerular apparatus, consistent with
      electrotonic vascular signal propagation. With a mathematical model of two
      coupled nephrons, we estimated the conductance of nephron coupling by fitting
      simulated vessel diameters to experimental data. With this value, we simulated
      nephron pairs to test for synchronization. In single-nephron simulations, the
      frequency of the TGF oscillation varied with nephron length. Coupling nephrons of
      different lengths forced TGF frequencies of both pair members to converge to a
      common value. The myogenic oscillations also synchronized, and the
      synchronization between the TGF and the myogenic oscillations showed an increased
      stability against parameter perturbations. Electronic vascular signal propagation
      is a plausible mechanism for nephron synchronization. Coupling increased the
      stability of the various oscillations.

PMID- 19116242
TI  - Nectin proteins are expressed at early stages of nephrogenesis and play a role in
      renal epithelial cell morphogenesis.
AB  - Development of the nephron requires conversion of the metanephric mesenchyme into
      tubular epithelial structures with specifically organized intercellular
      junctions. The nectin proteins are a family of transmembrane proteins that
      dimerize to form intercellular junctional complexes between epithelial cells. In
      this study, we demonstrate that nectin junctions appear during the earliest
      stages of epithelial cell morphogenesis in the murine nephron concurrently with
      the transition of mesenchymal cells into epithelial cells. We have defined the
      role of nectin during epithelial cell morphogenesis by studying nectin in a three
      dimensional culture of Madin-Darby canine kidney (MDCK) cells. In a three
      dimensional culture of MDCK cells grown in purified type 1 collagen, expression
      of a dominant negative form of nectin causes disruption of the formation of cell
      polarity and disruption of tight junction (TJ) formation, as measured by zonula
      occludens-1 (ZO-1) localization. In MDCK cells cultured in Matrigel, exogenous
      expression of nectin-1 causes disruption of normal epithelial cell cyst formation
      and decreased apoptosis. These data demonstrate that nectins play an important
      role in normal epithelial cell morphogenesis and may play a role in mesenchymal
      to-epithelial transition during nephrogenesis by providing an antiapoptotic
      signal and promoting the formation of TJs and cell polarity.

PMID- 19116243
TI  - Hemin therapy attenuates kidney injury in deoxycorticosterone acetate-salt
      hypertensive rats.
AB  - Upregulating the heme oxygenase (HO) system removes the prooxidant heme, and thus
      is cytoprotective. Additionally, the products from the HO pathway including,
      carbon monoxide, bilirubin, and biliverdin, scavenge reactive oxygen species,
      inhibit lipid peroxidation, and suppress tissue inflammation, while the iron
      formed enhances the synthesis of the antioxidant ferritin. Deoxycorticosterone
      acetate (DOCA)-salt hypertension, a model of human primary aldosteronism, causes
      oxidative stress and impairs renal function by stimulating inflammatory/oxidative
      transcription factors such as NF-kappaB and activating protein (AP-1). The effect
      of the HO system in end-organ damage in mineralocorticoid-induced hypertension
      has not been fully characterized. In this study, the administration of the HO
      inducer hemin lowered blood pressure (191 vs. 135 mmHg; n = 22, P < 0.01),
      increased creatinine clearance, and reduced kidney hypertrophy proteinuria,
      albuminuria, and histopathological lesions, including glomerular hypertrophy,
      glomerulosclerosis, tubular dilation, tubular cast formation, and interstitial
      mononuclear cell infiltration in nephrectomy/DOCA-high-salt-hypertension. The
      renoprotection was accompanied by reduced levels of NF-kappaB, AP-1, fibronectin,
      transforming growth factor (TGF)-beta, and 8-isoprostane, a marker of oxidative
      stress. Correspondingly, a robust increase in total antioxidant capacity, HO
      activity, cGMP, and an antioxidant like ferritin was observed in hemin-treated
      animals. Our findings suggest that suppression of oxidative/inflammatory insults
      alongside the corresponding decline of fibronectin and TGF-beta, an activator of
      extracellular matrix proteins, may account for the attenuation of renal
      histopathological lesions and the antihypertrophic effects of hemin. The
      multifaceted interaction among the HO system, TGF-beta, fibronectin, AP-1, and NF
      kappaB may be explored to design new drugs against end-stage-organ damage.

PMID- 19116244
TI  - SUMO-specific protease 1 (SENP1) reverses the hormone-augmented SUMOylation of
      androgen receptor and modulates gene responses in prostate cancer cells.
AB  - The acceptor sites for small ubiquitin-like modifier (SUMO) are conserved in the
      N-terminal domains of several nuclear receptors. Here, we show that androgens
      induce rapid and dynamic conjugation of SUMO-1 to androgen receptor (AR). Nuclear
      import of AR is not sufficient for SUMOylation, because constitutively nuclear
      apo-ARs or antagonist-bound ARs are only very weakly modified by SUMO-1 in
      comparison with agonist-bound ARs. Of the SUMO-specific proteases (SENP)-1, -2, 
      3, -5, and -6, only SENP1 and SENP2 are efficient in cleaving AR-SUMO-1
      conjugates in intact cells and in vitro. Both SENP1 and -2 are nuclear and found
      at sites proximal to AR. Their expression promotes AR-dependent transcription,
      but in a promoter-selective fashion. SENP1 and -2 stimulated the activity of holo
      AR on compound androgen response element-containing promoters. The effects of
      SENP1 and -2 on AR-dependent transcription were dependent on catalytic activity
      and required intact SUMO acceptor sites in AR, indicating that their coactivating
      effects are mainly due to their direct isopeptidase activity on holo-AR. In
      prostate cancer cells, ectopic expression of SENP1, but not that of SENP2,
      increased the transcription activity of endogenous AR. Silencing of SENP1
      attenuated the expression of several AR target genes and blunted androgen
      stimulated growth of LNCaP cells. Our results indicate that SENP1 reverses the
      ligand-induced SUMOylation of AR and helps fine tune the cellular responses to
      androgens in a target promoter-selective manner.

PMID- 19116245
TI  - Transcriptional regulation of the human growth hormone receptor (hGHR) gene V2
      promoter by transcriptional activators and repressor.
AB  - The V2 transcript is the major ubiquitously expressed human GH receptor (hGHR)
      mRNA in all tissues examined to date. In a previous investigation, we defined the
      V2 promoter as TATA-less and exhibiting many characteristics of a housekeeping
      gene promoter. We also demonstrated that its basal activity is determined by
      several different cis-regulatory regions within both the promoter and the V2
      exon. In the present study, we used luciferase-reporter, site-directed
      mutagenesis, gel shift, chromatin immunoprecipitation, and quantitative RT-PCR
      assays to investigate the ability of certain transcription factors to regulate
      hGHR V2 transcription through these regions in mammalian cells, including human
      adipocytes. Ets1 was found to transactivate the V2 proximal promoter through
      specific Ets sites. Two CCAAT/enhancer-binding protein (C/EBP) family members
      [C/EBP-homologous protein (CHOP) and C/EBPbeta] enhanced V2 transcription via
      different pathways: indirectly, by association with a V2 exon region (CHOP), and
      directly, using a V2 proximal promoter noncanonical binding site (C/EBPbeta). The
      Notch signaling mediator, Hes1, potently suppressed V2 promoter activity through
      interaction with two Hes sites within the V2 exon. We propose that these
      transcriptional factors regulate hGHR V2 expression by acting as downstream
      nuclear effectors, linking specific signaling cascades (e.g. MAPK and Notch)
      triggered by different growth factor-, development-, and nutrition- as well as
      stress-related stimuli. Our data also suggest that these factors are likely to be
      important in the differentiation-induced increase in V2 mRNA expression in
      adipocytes, with Ets1 and CHOP functioning at the preadipocyte stage to prepare
      the cells for differentiation and increasing C/EBPs and decreasing Hes1 levels
      contributing during adipocyte maturation.

PMID- 19116246
TI  - Structure and activity of the human growth hormone receptor (hGHR) gene V2
      promoter.
AB  - Human GH (hGH) has important effects on growth as well as carbohydrate, fat, and
      protein metabolism. These actions require the presence of normal levels of a
      functional hGH receptor (hGHR) on the surface of target cells. hGHR gene
      expression is characterized by the use of several 5'-noncoding exons and
      alternative splicing, resulting in the generation of multiple mRNA isoforms. The
      hGHR V2 transcript is predominant in most tissues, including human fat. However,
      factors regulating its ubiquitous expression have remained unidentified. The
      present study was aimed at characterizing the mechanisms regulating hGHR V2
      transcription. Two major V2 transcriptional start sites were identified by primer
      extension assays. The V2 proximal promoter is TATA-less, with several
      characteristics of a housekeeping gene promoter. Transient transfection analyses
      of 2.6 kb of the 5'-flanking region of V2 confirmed its promoter activity in
      multiple primate cell lines. Similar promoter activity patterns were observed in
      human SGBS preadipocytes and mature adipocytes but with much higher V2 promoter
      activity in mature adipocytes, suggesting that changes in the availability of
      specific factors during adipocyte differentiation play a role in V2 promoter
      regulation. Serial deletion and mutation analyses revealed that transcription of
      hGHR V2 in different cell types, including adipocytes, is determined by a core
      promoter and distinct inhibitory and activation domains in the 5'-promoter region
      as well as within the V2 exon. Our data suggest that V2 transcription is the
      result of a complex interplay involving multiple factors, to ensure appropriate
      expression of hGHR in different hGH target cells.

PMID- 19116247
TI  - Transcriptional profiling of human mesenchymal stem cells transduced with
      reporter genes for imaging.
AB  - Mesenchymal stem cells (MSCs) can differentiate into osteogenic, adipogenic,
      chondrogenic, myocardial, or neural lineages when exposed to specific stimuli,
      making them attractive for tissue repair and regeneration. We have used reporter
      gene-based imaging technology to track MSC transplantation or implantation in
      vivo. However, the effects of lentiviral transduction with the fluc-mrfp-ttk
      triple-fusion vector on the transcriptional profiles of MSCs remain unknown. In
      this study, gene expression differences between wild-type and transduced hMSCs
      were evaluated using an oligonucleotide human microarray. Significance Analysis
      of Microarray identified differential genes with high accuracy; RT-PCR validated
      the microarray results. Annotation analysis showed that transduced hMSCs
      upregulated cell differentiation and antiapoptosis genes while downregulating
      cell cycle, proliferation genes. Despite transcriptional changes associated with
      bone and cartilage remodeling, their random pattern indicates no systematic
      change of crucial genes that are associated with osteogenic, adipogenic, or
      chondrogenic differentiation. This correlates with the experimental results that
      lentiviral transduction did not cause the transduced MSCs to lose their basic
      stem cell identity as demonstrated by osteogenic, chondrogenic, and adipogenic
      differentiation assays with both transduced and wild-type MSCs, although a
      certain degree of alterations occurred. Histological analysis demonstrated
      osteogenic differentiation in MSC-loaded ceramic cubes in vivo. In conclusion,
      transduction of reporter genes into MSCs preserved the basic properties of stem
      cells while enabling noninvasive imaging in living animals to study the
      biodistribution and other biological activities of the cells.

PMID- 19116248
TI  - Transcriptional and functional differences in stem cell populations isolated from
      extraocular and limb muscles.
AB  - The extraocular muscles (EOMs) are a distinct muscle group that displays an array
      of unique contractile, structural, and regenerative properties. They also have
      differential sensitivity to certain diseases and are enigmatically spared in
      Duchenne muscular dystrophy (DMD). The EOMs are so distinct from other skeletal
      muscles that the term "allotype" has been coined to highlight EOM group-specific
      properties. We hypothesized that increased and distinct stem cells may underlie
      the continual myogenesis noted in EOM. The side population (SP) stem cells were
      isolated and studied. EOMs had 15x higher SP cell content compared with limb
      muscles. Expression profiling revealed 348 transcripts that define the EOM-SP
      transcriptome. Over 92% of transcripts were SP specific, because they were absent
      in previous whole muscle microarray studies. Cultured EOM-SP cells revealed
      superior in vitro proliferative capacity. Finally, assays of the committed
      progenitors or satellite cells performed on myofibers isolated from EOM and limb
      muscles independently validated the increased proliferative capacity of these
      muscles. We suggest a model in which unique EOM stem cells contribute to the
      continual myogenesis noted in EOM and consistent with a role for their sparing in
      DMD. We believe the greater numbers of stem cells, their unique transcriptome,
      the greater proliferative capacity of EOM stem cells, and the greater number of
      satellite cells also offer clues for novel cell-based therapeutic strategies.

PMID- 19116249
TI  - Human immunodeficiency virus type 1 population genetics and adaptation in newly
      infected individuals.
AB  - Studies on human immunodeficiency virus type 1 (HIV-1) diversity are critical for
      understanding viral pathogenesis and the emergence of immune escape variants and
      for design of vaccine strategies. To investigate HIV-1 population genetics, we
      used single-genome sequencing to obtain pro-pol and env sequences from
      longitudinal samples (n = 93) from 14 acutely or recently infected patients. The
      first available sample after infection for 12/14 patients revealed HIV-1
      populations with low genetic diversity, consistent with transmission or outgrowth
      of a single variant. In contrast, two patients showed high diversity and
      coexistence of distinct virus populations in samples collected days after a
      nonreactive enzyme-linked immunosorbent assay or indeterminate Western blot,
      consistent with transmission or outgrowth of multiple variants. Comparison of PR
      and RT sequences from the first sample for all patients with the consensus
      subgroup B sequence revealed that nearly all nonsynonymous differences were
      confined to identified cytotoxic T-lymphocyte (CTL) epitopes. For HLA-typed
      patients, mutations compared to the consensus in transmitted variants were found
      in epitopes that would not be recognized by the patient's major
      histocompatibility complex type. Reversion of transmitted mutations was rarely
      seen over the study interval (up to 5 years). These data indicate that acute
      subtype B HIV-1 infection usually results from transmission or outgrowth of
      single viral variants carrying mutations in CTL epitopes that were selected prior
      to transmission either in the donor or in a previous donor and that reversion of
      these mutations can be very slow. These results have important implications for
      vaccine strategies because they imply that some HLA alleles could be compromised
      in newly acquired HIV infections.

PMID- 19116250
TI  - Identification of the nuclear export and adjacent nuclear localization signals
      for ORF45 of Kaposi's sarcoma-associated herpesvirus.
AB  - Open reading frame 45 (ORF45) of Kaposi's sarcoma-associated herpesvirus 8 (KSHV)
      is an immediate-early phosphorylated tegument protein and has been shown to play
      important roles at both early and late stages of viral infection. Homologues of
      ORF45 exist only in gammaherpesviruses, and their homology is limited. These
      homologues differ in their protein lengths and subcellular localizations. We and
      others have reported that KSHV ORF45 is localized predominantly in the cytoplasm,
      whereas its homologue in murine herpesvirus 68 is localized exclusively in the
      nucleus. We observed that ORF45s of rhesus rhadinovirus and herpesvirus saimiri
      are found exclusively in the nucleus. As a first step toward understanding the
      mechanism underlying the distinct intracellular distribution of KSHV ORF45, we
      identified the signals that control its subcellular localization. We found that
      KSHV ORF45 accumulated rapidly in the nucleus in the presence of leptomycin B, an
      inhibitor of CRM1 (exportin 1)-dependent nuclear export, suggesting that it could
      shuttle between the nucleus and cytoplasm. Mutational analysis revealed that KSHV
      ORF45 contains a CRM1-dependent, leucine-rich-like nuclear export signal and an
      adjacent nuclear localization signal. Replacement of the key residues with
      alanines in these motifs of ORF45 disrupts its shuttling between the cytoplasm
      and nucleus. The resulting ORF45 mutants have restricted subcellular
      localizations, being found exclusively either in the cytoplasm or in the nucleus.
      Recombinant viruses were reconstituted by introduction of these mutations into
      KSHV bacterial artificial chromosome BAC36. The resultant viruses have distinct
      phenotypes. A mutant virus in which ORF45 is restricted to the cytoplasm behaves
      as an ORF45-null mutant and produces 5- to 10-fold fewer progeny viruses than the
      wild type. In contrast, mutants in which the ORF45 protein is mostly restricted
      to the nucleus produce numbers of progeny viruses similar to those produced by
      the wild type. These data suggest that the subcellular localization signals of
      ORF45 have important functional roles in KSHV lytic replication.

PMID- 19116251
TI  - Treatment of chronic viral hepatitis in woodchucks by prolonged intrahepatic
      expression of interleukin-12.
AB  - Chronic hepatitis B is a major cause of liver-related death worldwide.
      Interleukin-12 (IL-12) induction accompanies viral clearance in chronic hepatitis
      B virus infection. Here, we tested the therapeutic potential of IL-12 gene
      therapy in woodchucks chronically infected with woodchuck hepatitis virus (WHV),
      an infection that closely resembles chronic hepatitis B. The woodchucks were
      treated by intrahepatic injection of a helper-dependent adenoviral vector
      encoding IL-12 under the control of a liver-specific RU486-responsive promoter.
      All woodchucks with viral loads below 10(10) viral genomes (vg)/ml showed a
      marked and sustained reduction of viremia that was accompanied by a reduction in
      hepatic WHV DNA, a loss of e antigen and surface antigen, and improved liver
      histology. In contrast, none of the woodchucks with higher viremia levels
      responded to therapy. The antiviral effect was associated with the induction of T
      cell immunity against viral antigens and a reduction of hepatic expression of
      Foxp3 in the responsive animals. Studies were performed in vitro to elucidate the
      resistance to therapy in highly viremic woodchucks. These studies showed that
      lymphocytes from healthy woodchucks or from animals with low viremia levels
      produced gamma interferon (IFN-gamma) upon IL-12 stimulation, while lymphocytes
      from woodchucks with high viremia failed to upregulate IFN-gamma in response to
      IL-12. In conclusion, IL-12-based gene therapy is an efficient approach to treat
      chronic hepadnavirus infection in woodchucks with viral loads below 10(10) vg/ml.
      Interestingly, this therapy is able to break immunological tolerance to viral
      antigens in chronic WHV carriers.

PMID- 19116252
TI  - EBNA3C can modulate the activities of the transcription factor Necdin in
      association with metastasis suppressor protein Nm23-H1.
AB  - Previous studies have demonstrated the interaction between the Epstein-Barr virus
      (EBV) nuclear antigen 3C (EBNA3C) and the metastatic suppressor Nm23-H1 both in
      vitro and in vivo (C. Subramanian, M. A. Cotter II, and E. S. Robertson, Nat.
      Med. 7:350-355, 2001). Importantly EBNA3C can reverse the ability of Nm23-H1 to
      suppress migration of human cells in vitro. EBNA3C contributes to EBV-associated
      human cancers by regulating transcription of a number of cellular and viral
      promoters as well as targeting and altering the transcription activities of the
      metastasis suppressor Nm23-H1. Furthermore, Necdin is a cellular protein which is
      highly induced in terminally differentiated cells; it contributes to the
      regulation of cell growth and is also known to interact with viral oncoproteins.
      In this report, we show that Nm23-H1 and EBNA3C can modulate the biological
      functions of Necdin in the context of EBV infection and transformation. The
      levels of Necdin were consistently lower in EBV-positive cells, and EBNA3C could
      change the subcellular localization of Necdin as well as rescue cells from the
      antiangiogenic and antiproliferative effects mediated by Necdin. We also show
      that Necdin directly interacts with Nm23-H1, resulting in modulation of the
      biochemical function of Nm23-H1 as well as the biological function of Necdin.
      Both EBNA3C and Nm23-H1 were able to rescue not only Necdin-mediated
      transcriptional repression of the downstream vascular endothelial growth factor
      promoter but also Necdin-mediated growth suppression and antiangiogenic effects
      on cancer cells. The majority of this response was mediated through amino acid
      residues 191 to 222 of Necdin, which are also known to be important for nuclear
      matrix targeting. These studies suggest a role for Necdin in the regulation of
      downstream cellular targets in a hypoxic environment in virus-associated human
      cancers.

PMID- 19116253
TI  - HLA-B57/B*5801 human immunodeficiency virus type 1 elite controllers select for
      rare gag variants associated with reduced viral replication capacity and strong
      cytotoxic T-lymphocyte [corrected] recognition.
AB  - Human immunodeficiency virus type 1 (HIV-1) elite controllers (EC) maintain
      viremia below the limit of commercial assay detection (<50 RNA copies/ml) in the
      absence of antiviral therapy, but the mechanisms of control remain unclear. HLA
      B57 and the closely related allele B*5801 are particularly associated with
      enhanced control and recognize the same Gag(240-249) TW10 epitope. The typical
      escape mutation (T242N) within this epitope diminishes viral replication capacity
      in chronically infected persons; however, little is known about TW10 epitope
      sequences in residual replicating viruses in B57/B*5801 EC and the extent to
      which mutations within this epitope may influence steady-state viremia. Here we
      analyzed TW10 in a total of 50 B57/B*5801-positive subjects (23 EC and 27 viremic
      subjects). Autologous plasma viral sequences from both EC and viremic subjects
      frequently harbored the typical cytotoxic T-lymphocyte (CTL)-selected mutation
      T242N (15/23 sequences [65.2%] versus 23/27 sequences [85.1%], respectively; P =
      0.18). However, other unique mutants were identified in HIV controllers, both
      within and flanking TW10, that were associated with an even greater reduction in
      viral replication capacity in vitro. In addition, strong CTL responses to many of
      these unique TW10 variants were detected by gamma interferon-specific enzyme
      linked immunospot assay. These data suggest a dual mechanism for durable control
      of HIV replication, consisting of viral fitness loss resulting from CTL escape
      mutations together with strong CD8 T-cell immune responses to the arising variant
      epitopes.

PMID- 19116254
TI  - Cell type-specific induction and inhibition of apoptosis by Herpes Simplex virus
      type 2 ICP10.
AB  - Herpes simplex virus (HSV) inhibits apoptosis induced by external stimuli in
      epithelial cells. In contrast, apoptosis is the primary outcome in HSV-infected
      lymphocytes. Here, we show that HSV type 2 (HSV-2) gene expression appears to be
      necessary for the induction of apoptosis in Jurkat cells, a T-cell leukemia line.
      HSV-2 ICP10 gene expression is sufficient to induce apoptosis in Jurkat cells,
      while its expression protects epithelial HEp-2 cells from apoptosis triggered by
      cycloheximide and tumor necrosis factor alpha. Thus, the effect of HSV-2 gene
      expression on the cellular apoptotic pathway appears to depend on the specific
      cell type.

PMID- 19116255
TI  - Major tegument protein pp65 of human cytomegalovirus is required for the
      incorporation of pUL69 and pUL97 into the virus particle and for viral growth in
      macrophages.
AB  - The tegument protein pp65 of human cytomegalovirus (HCMV) represents the major
      component of mature virus particles. Nevertheless, deletion of pp65 has been
      shown to have no effects on virus replication and morphogenesis in fibroblasts in
      vitro. We have studied the HCMV virion composition in the absence of pp65 and
      viral growth of a pp65 stop mutant in different cell types, including monocyte
      derived macrophages. Two stop codons at amino acids 11 and 12 of pp65 were
      introduced by bacterial artificial chromosome mutagenesis into the
      endotheliotropic strain TB40/E. Clear changes of the tegument composition could
      be observed in purified mutant virus particles, where the amount of tegument
      protein pUL25 was drastically reduced. In addition, pUL69 and the virally encoded
      protein kinase UL97 were undetectable in the pp65 stop mutant. Expression of
      pUL69 in infected cells was unaltered while pUL25 accumulated in the absence of
      pp65, thus demonstrating that only incorporation into virus particles is
      dependent on pp65. Coimmunoprecipitation experiments using lysates of infected
      cells revealed an interaction between pUL69 and pp65. This interaction was
      verified in pull-down experiments using transfected cells, which showed that pp65
      and pUL69 do not require the presence of other viral proteins for their
      interaction. We conclude that pp65 is required for the incorporation of other
      viral proteins into the virus particle and thus is involved in the protein
      protein interaction network leading to normal tegument formation. When studying
      growth kinetics of the pp65 stop mutant in different cell types, we found a
      severe impairment of viral growth in monocyte-derived macrophages, showing for
      the first time a strong cell-specific role of pp65 in viral growth.

PMID- 19116257
TI  - Host immune responses to chronic adenovirus infections in human and nonhuman
      primates.
AB  - Recent studies indicate that great apes and macaques chronically shed
      adenoviruses in the stool. Shedding of adenovirus in the stool of humans is less
      prevalent, although virus genomes persist in gut-associated lymphoid tissue in
      the majority of individual samples. Chimpanzees have high levels of broadly
      reactive neutralizing antibodies to adenoviruses in serum, with very low
      frequencies of adenovirus-specific T cells in peripheral blood. A similar
      situation exists in macaques; sampling of guts from macaques demonstrated
      adenovirus-specific T cells in lamina propria. Humans show intermediate levels of
      serum neutralizing antibodies, with adenovirus-specific T cells in peripheral
      blood of all individuals sampled and about 20% of samples from the gut,
      suggesting a potential role of T cells in better controlling virus replication in
      the gut. The overall structure of the E3 locus, which is involved in modulating
      the host's response to infection, is degenerate in humans compared to that in
      apes, which may contribute to diminished evasion of host immunity. The impact of
      adenovirus persistence and immune responses should be considered when using
      adenoviral vectors in gene therapy and genetic vaccines.

PMID- 19116256
TI  - Ecology, genetic diversity, and phylogeographic structure of andes virus in
      humans and rodents in Chile.
AB  - Andes virus (ANDV) is the predominant etiologic agent of hantavirus
      cardiopulmonary syndrome (HCPS) in southern South America. In Chile,
      serologically confirmed human hantavirus infections have occurred throughout a
      wide latitudinal distribution extending from the regions of Valparaiso (32 to 33
      degrees S) to Aysen (46 degrees S) in southern Patagonia. In this study, we found
      seropositive rodents further north in the Coquimbo region (30 degrees S) in
      Chile. Rodent seroprevalence was 1.4%, with Oligoryzomys longicaudatus displaying
      the highest seroprevalence (5.9%), followed by Abrothrix longipilis (1.9%) and
      other species exhibiting </=0.6% seropositivity. We sequenced partial ANDV small
      (S) segment RNA from 6 HCPS patients and 32 rodents of four different species
      collected throughout the known range of hantavirus infection in Chile.
      Phylogenetic analyses showed two major ANDV South (ANDV Sout) clades, congruent
      with two major Chilean ecoregions, Mediterranean (Chilean matorral [shrubland])
      and Valdivian temperate forest. Human and rodent samples grouped according to
      geographic location. Phylogenetic comparative analyses of portions of S and
      medium segments (encoding glycoproteins Gn and Gc) from a subset of rodent
      specimens exhibited similar topologies, corroborating two major ANDV Sout clades
      in Chile and suggesting that yet unknown factors influence viral gene flow and
      persistence throughout the two Chilean ecoregions. Genetic algorithms for
      recombination detection identified recombination events within the S segment.
      Molecular demographic analyses showed that the virus is undergoing purifying
      selection and demonstrated a recent exponential growth in the effective number of
      ANDV Sout infections in Chile that correlates with the increased number of human
      cases reported. Although we determined virus sequences from four rodent species,
      our results confirmed O. longicaudatus as the primary ANDV Sout reservoir in
      Chile. While evidence of geographic differentiation exists, a single cosmopolitan
      lineage of ANDV Sout remains the sole etiologic agent for HCPS in Chile.

PMID- 19116258
TI  - Discovery of a novel single-stranded DNA virus from a sea turtle fibropapilloma
      by using viral metagenomics.
AB  - Viral metagenomics, consisting of viral particle purification and shotgun
      sequencing, is a powerful technique for discovering viruses associated with
      diseases with no definitive etiology, viruses that share limited homology with
      known viruses, or viruses that are not culturable. Here we used viral
      metagenomics to examine viruses associated with sea turtle fibropapillomatosis
      (FP), a debilitating neoplastic disease affecting sea turtles worldwide. By means
      of purifying and shotgun sequencing the viral community directly from the
      fibropapilloma of a Florida green sea turtle, a novel single-stranded DNA virus,
      sea turtle tornovirus 1 (STTV1), was discovered. The single-stranded, circular
      genome of STTV1 was approximately 1,800 nucleotides in length. STTV1 has only
      weak amino acid level identities (25%) to chicken anemia virus in short regions
      of its genome; hence, STTV1 may represent the first member of a novel virus
      family. A total of 35 healthy turtles and 27 turtles with FP were tested for
      STTV1 using PCR, and only 2 turtles severely afflicted with FP were positive. The
      affected turtles were systemically infected with STTV1, since STTV1 was found in
      blood and all major organs. STTV1 exists as a quasispecies, with several genome
      variants identified in the fibropapilloma of each positive turtle, suggesting
      rapid evolution of this virus. The STTV1 variants were identical over the
      majority of their genomes but contained a hypervariable region with extensive
      divergence. This study demonstrates the potential of viral metagenomics for
      discovering novel viruses directly from animal tissue, which can enhance our
      understanding of viral evolution and diversity.

PMID- 19116259
TI  - Mobilization of endogenous retroviruses in mice after infection with an exogenous
      retrovirus.
AB  - Mammalian genomes harbor a large number of retroviral elements acquired as germ
      line insertions during evolution. Although many of the endogenous retroviruses
      are defective, several contain one or more intact viral genes that are expressed
      under certain physiological or pathological conditions. This is true of the
      endogenous polytropic retroviruses that generate recombinant polytropic murine
      leukemia viruses (MuLVs). In these recombinants the env gene sequences of
      exogenous ecotropic MuLVs are replaced with env gene sequences from an endogenous
      polytropic retrovirus. Although replication-competent endogenous polytropic
      retroviruses have not been observed, the recombinant polytropic viruses are
      capable of replicating in numerous species. Recombination occurs during reverse
      transcription of a virion RNA heterodimer comprised of an RNA transcript from an
      endogenous polytropic virus and an RNA transcript from an exogenous ecotropic
      MuLV RNA. It is possible that homodimers corresponding to two full-length
      endogenous RNA genomes are also packaged. Thus, infection by an exogenous virus
      may result not only in recombination with endogenous sequences, but also in the
      mobilization of complete endogenous retrovirus genomes via pseudotyping within
      exogenous retroviral virions. We report that the infection of mice with an
      ecotropic virus results in pseudotyping of intact endogenous viruses that have
      not undergone recombination. The endogenous retroviruses infect and are
      integrated into target cell genomes and subsequently replicate and spread as
      pseudotyped viruses. The mobilization of endogenous retroviruses upon infection
      with an exogenous retrovirus may represent a major interaction of exogenous
      retroviruses with endogenous retroviruses and may have profound effects on the
      pathogenicity of retroviral infections.

PMID- 19116260
TI  - Widely conserved recombination patterns among single-stranded DNA viruses.
AB  - The combinatorial nature of genetic recombination can potentially provide
      organisms with immediate access to many more positions in sequence space than can
      be reached by mutation alone. Recombination features particularly prominently in
      the evolution of a diverse range of viruses. Despite rapid progress having been
      made in the characterization of discrete recombination events for many species,
      little is currently known about either gross patterns of recombination across
      related virus families or the underlying processes that determine genome-wide
      recombination breakpoint distributions observable in nature. It has been
      hypothesized that the networks of coevolved molecular interactions that define
      the epistatic architectures of virus genomes might be damaged by recombination
      and therefore that selection strongly influences observable recombination
      patterns. For recombinants to thrive in nature, it is probably important that the
      portions of their genomes that they have inherited from different parents work
      well together. Here we describe a comparative analysis of recombination
      breakpoint distributions within the genomes of diverse single-stranded DNA
      (ssDNA) virus families. We show that whereas nonrandom breakpoint distributions
      in ssDNA virus genomes are partially attributable to mechanistic aspects of the
      recombination process, there is also a significant tendency for recombination
      breakpoints to fall either outside or on the peripheries of genes. In particular,
      we found significantly fewer recombination breakpoints within structural protein
      genes than within other gene types. Collectively, these results imply that
      natural selection acting against viruses expressing recombinant proteins is a
      major determinant of nonrandom recombination breakpoint distributions observable
      in most ssDNA virus families.

PMID- 19116261
TI  - Dopamine is a low-affinity and high-specificity substrate for the human UDP
      glucuronosyltransferase 1A10.
AB  - The purpose of this work was to identify human UDP-glucuronosyltransferases
      (UGTs) capable of glucuronidating dopamine. Using a sensitive liquid
      chromatography-tandem mass spectrometry method, we screened all 19 known human
      UGTs and found that only one enzyme, UGT1A10, catalyzed dopamine glucuronidation
      at substantial rates, yielding both dopamine-4-O-glucuronide (37.1 pmol/min/mg)
      and dopamine-3-O-glucuronide (32.7 pmol/min/mg). Much lower (<2 pmol/min/mg) or
      no dopamine glucuronidation activity was found for all other UGTs tested at 1 mM
      dopamine. Evaluation of the UGT1A10 expression pattern in human tissues by
      quantitative reverse transcription-polymerase chain reaction confirmed that it is
      mainly expressed in small intestine, colon, and adipose tissue, whereas only low
      levels were found in trachea, stomach, liver, testis, and prostate but not in
      brain. Dopamine glucuronidation assays using microsomes from human liver and
      intestine corroborated these findings because activity in intestinal microsomes
      was markedly higher than that in liver microsomes. Moreover, the glucuronidation
      regioselectivity in intestinal microsomes was similar to that of recombinant
      UGT1A10, and both enzyme sources exhibited sigmoidal kinetics with substrate
      affinity (K(A)) values in the range of 2 to 3 mM. Examination of four UGT1A10
      mutants, F90A, F90L, F93A, and F93L, revealed lower dopamine glucuronidation in
      all of them, particularly in F90A and F93A. Nonetheless, the substrate affinities
      of the four mutants were similar to that of UGT1A10. It is interesting to note
      that mutant F93L exhibited regioselectivity, conjugating dopamine at the 4
      hydroxyl (OH) position approximately 3 times more efficiently than at the 3-OH
      position. These results shed new light on the structure and function of UGT1A10
      and indicate that dopamine may be a useful probe substrate for this enzyme.

PMID- 19116262
TI  - Metabolism of vitamin d2 to 17,20,24-trihydroxyvitamin d2 by cytochrome p450scc
      (CYP11A1).
AB  - As well as catalyzing the conversion of cholesterol to pregnenolone for steroid
      synthesis, cytochrome P450scc (P450scc) can also metabolize vitamins D2 (D2) and
      D3 (D3). Two products of D2 metabolism by P450scc, 20-hydroxyvitamin D2 and 17,20
      dihydroxyvitamin D2, have been identified and shown to exert biological activity
      on cultured keratinocytes. The aim of this study was to fully characterize the
      metabolism of D2 by P450scc, including identifying additional products and
      determining the kinetics of D2 metabolism. Two new products were isolated by
      reverse-phase high-performance liquid chromatography: a dihydroxy metabolite with
      a hydroxyl group at C20 plus another unidentified position, and a trihydroxy
      metabolite identified by NMR as 17,20,24-trihydroxyvitamin D2. Kinetics of D2
      metabolism was determined with substrate solubilized by 2-hydroxypropyl-beta
      cyclodextrin or incorporated into phospholipid vesicles. In 2-hydroxypropyl-beta
      cyclodextrin, D2 was hydroxylated at C20 with a k(cat)/K(m) 5-fold lower than
      that for cholesterol metabolism. 20-Hydroxyvitamin D2 was hydroxylated with a
      similar k(cat)/K(m) to D2, whereas 17,20-dihydroxyvitamin D2 was hydroxylated
      with a lower k(cat)/K(m) than that for D2 in 2-hydroxypropyl-beta-cyclodextrin.
      In vesicles, D2 displayed a high K(m) relative to that for cholesterol, but
      hydroxylation resulted in products that could be further hydroxylated with
      relatively low K(m) values. We conclude that P450scc catalyzes three sequential
      hydroxylations of D2 producing 20-hydroxyvitamin D2, 17,20-dihydroxyvitamin D2,
      and 17,20,24-trihydroxyvitamin D2, which dissociate from the active site of
      P450scc and accumulate in the reaction mixture. D2 metabolism occurs with lower
      efficiency (k(cat)/K(m)) than that observed for both cholesterol and D3
      metabolism by P450scc.

PMID- 19116263
TI  - Clonidine pharmacokinetics in pregnancy.
AB  - The objective of this study was to determine the pharmacokinetic parameters of
      clonidine during pregnancy compared with previously published data in nonpregnant
      subjects. Serial blood and urine samples were collected in 17 women during mid to
      late pregnancy over one steady-state dosing interval to determine clonidine
      noncompartmental pharmacokinetic parameters (n = 17) and creatinine clearance. In
      six of these pregnant subjects, maternal and umbilical cord (venous and arterial)
      plasma samples were collected at the time of delivery for measurement of
      clonidine concentrations. Clonidine apparent oral clearance was found to be 440
      +/- 168 ml/min during pregnancy compared with 245 +/- 72 ml/min as previously
      reported in nonpregnant subjects (p < 0.0001) (Cunningham et al., 1994). There
      was a strong correlation (r = 0.82, p < 0.001) between clonidine renal clearance,
      adjusted for variation in glomerular filtration rate, and urine pH. Umbilical
      cord to maternal plasma clonidine concentration ratios were 1.0 +/- 0.1
      (arterial) and 1.0 +/- 0.1 (venous). In conclusion, clonidine is cleared more
      rapidly in pregnant women than in nonpregnant subjects. At the time of delivery,
      the fetus is exposed to similar plasma clonidine concentrations as the mother.

PMID- 19116264
TI  - Disposition of the herbicide 2-chloro-4-(ethylamino)-6-(isopropylamino)-s
      triazine (Atrazine) and its major metabolites in mice: a liquid
      chromatography/mass spectrometry analysis of urine, plasma, and tissue levels.
AB  - 2-Chloro-4-(ethylamino)-6-(isopropylamino)-s-triazine (atrazine, ATR) is a
      toxicologically important and widely used herbicide. Recent studies have shown
      that it can elicit neurological, immunological, developmental, and biochemical
      alterations in several model organisms, including in mice. Because disposition
      data in mice are lacking, we evaluated ATR's metabolism and tissue dosimetry
      after single oral exposures (5-250 mg/kg) in C57BL/6 mice using liquid
      chromatography/mass spectrometry (Ross and Filipov, 2006). ATR was metabolized
      and cleared rapidly; didealkyl ATR (DACT) was the major metabolite detected in
      urine, plasma, and tissues. Plasma ATR peaked at 1 h postdosing and rapidly
      declined, whereas DACT peaked at 2 h and slowly declined. Most ATR and metabolite
      residues were excreted within the first 24 h. However, substantial amounts of
      DACT were still present in 25- to 48-h and 49- to 72-h urine. ATR reached maximal
      brain levels (0.06-1.5 microM) at 4 h (5-125 mg/kg) and 1 h (250 mg/kg) after
      dosing, but levels quickly declined to <0.1 microM by 12 h in all the groups. In
      contrast, strikingly high concentrations of DACT (1.5-50 microM), which are
      comparable with liver DACT levels, were detectable in brain at 2 h. Brain DACT
      levels slowly declined, paralleling the kinetics of plasma DACT. Our findings
      suggest that in mice ATR is widely distributed and extensively metabolized and
      that DACT is a major metabolite detected in the brain at high levels and is
      ultimately excreted in urine. Our study provides a starting point for the
      establishment of models that link target tissue dose to biological effects caused
      by ATR and its in vivo metabolites.

PMID- 19116265
TI  - Unbound drug concentration in brain homogenate and cerebral spinal fluid at
      steady state as a surrogate for unbound concentration in brain interstitial
      fluid.
AB  - The objective of the present study was to examine the accuracy of using unbound
      brain concentration determined by a brain homogenate method (C(ub)), cerebral
      spinal fluid concentration (C(CSF)), and unbound plasma concentration (C(up)) as
      a surrogate for brain interstitial fluid concentration determined by brain
      microdialysis (C(m)). Nine compounds-carbamazepine, citalopram, ganciclovir,
      metoclopramide, N-desmethylclozapine, quinidine, risperidone, 9
      hydroxyrisperidone, and thiopental-were selected, and each was administered as an
      intravenous bolus (up to 5 mg/kg) followed by a constant intravenous infusion (1
      9 mg/kg/h) for 6 h in rats. For eight of the nine compounds, the C(ub)s were
      within 3-fold of their C(m); thiopental had a C(m) 4-fold of its C(ub). The
      C(CSF)s of eight of the nine compounds were within 3-fold of their corresponding
      C(m); 9-hydroxyrisperidone showed a C(CSF) 5-fold of its C(m). The C(up)s of five
      of the nine compounds were within 3-fold of their C(m); four compounds
      (ganciclovir, metoclopramide, quinidine, and 9-hydroxyrisperidone) had C(up)s 6-
      to 14-fold of their C(m). In conclusion, the C(ub) and C(CSF) were within 3-fold
      of the C(m) for the majority of the compounds tested. The C(up)s were within 3
      fold of C(m) for lipophilic non-P-glycoprotein (-P-gp) substrates and greater
      than 3-fold of C(m) for hydrophilic or P-gp substrates. The present study
      indicates that the brain homogenate and cerebral spinal fluid methods may be used
      as surrogate methods to predict brain interstitial fluid concentrations within 3
      fold of error in drug discovery and development settings.

PMID- 19116266
TI  - A reappraisal of evidence for probabilistic models of allelic exclusion.
AB  - B cell development requires the coordinated rearrangement of Ig heavy (IgH) and
      light chain loci (IgL). Most mature B cells express a single B cell receptor of
      unique specificity, and a central question in immunology concerns the mechanisms
      that prevent the productive rearrangement of >1 IgH and IgL allele per cell.
      Probabilistic models of allelic exclusion maintain that simultaneous
      rearrangement of both alleles is rare, because the likelihood of undergoing
      rearrangement is low for a given Ig allele. Strong support for this idea came
      from studies in which a GFP marker was inserted into the Igk locus. In this
      system, the probability of high-level germ-line transcription and subsequent
      locus rearrangement appeared to be low in pre-B cells. Readdressing the validity
      of GFP expression as a reporter for the level of germ-line transcription, we
      found a striking discordance between GFP transcript and protein levels at the pre
      B cell stage, which is explained at least in part by the developmentally
      regulated usage of 2 alternative Igk-J germ-line promoters. These results
      question the validity of the kappa-GFP system as evidence for probabilistic
      models of allelic exclusion.

PMID- 19116267
TI  - Changes in H5N1 influenza virus hemagglutinin receptor binding domain affect
      systemic spread.
AB  - The HA of influenza virus is a receptor-binding and fusion protein that is
      required to initiate infection. The HA receptor-binding domain determines the
      species of sialyl receptors recognized by influenza viruses. Here, we demonstrate
      that changes in the HA receptor-binding domain alter the ability of the H5N1
      virus to spread systemically in mice. The A/Vietnam/1203/04 (VN1203) and A/Hong
      Kong/213/03 (HK213) viruses are consistently lethal to domestic chickens but
      differ in their pathogenicity to mammals. Insertion of the VN1203 HA and
      neuraminidase (NA) genes into recombinant HK213 virus expanded its tissue tropism
      and increased its lethality in mice; conversely, insertion of HK213 HA and NA
      genes into recombinant VN1203 virus decreased its systemic spread and lethality.
      The VN1203 and HK213 HAs differ by 10 aa, and HK213 HA has shown greater binding
      affinity for synthetic alpha2,6-linked sialyl receptor. Introduction of an S227N
      change and removal of N-linked glycosylation at residue 158 increased the
      alpha2,6-binding affinity of VN1203 HA. Recombinant VN1203 virus carrying the
      S227N change alone or with the residue-158 glycosylation site removed showed
      reduced lethality and systemic spread in mice but not in domestic chickens. Wild
      type VN1203 virus exhibited the greatest efficiency in systemic spread after
      intramuscular inoculation and in infection of mouse bone marrow-derived dendritic
      cells and conventional pulmonary dendritic cells. These results show that VN1203
      HA glycoprotein confers pathogenicity by facilitating systemic spread in mice;
      they also suggest that a minor change in receptor binding domain may modulate the
      virulence of H5N1 viruses.

PMID- 19116268
TI  - Biallelic, ubiquitous transcription from the distal germline Ig{kappa} locus
      promoter during B cell development.
AB  - Allelic exclusion of Ig gene expression is necessary to limit the number of
      functional receptors to one per B cell. The mechanism underlying allelic
      exclusion is unknown. Because germline transcription of Ig and TCR loci is
      tightly correlated with rearrangement, we created two novel knock-in mice that
      report transcriptional activity of the Jkappa germline promoters in the Igkappa
      locus. Analysis of these mice revealed that germline transcription is biallelic
      and occurs in all pre-B cells. Moreover, we found that the two germline promoters
      in this region are not equivalent but that the distal promoter accounts for the
      vast majority of observed germline transcript in pre-B cells while the activity
      of the proximal promoter increases later in development. Allelic exclusion of the
      Igkappa locus thus occurs at the level of rearrangement, but not germline
      transcription.

PMID- 19116269
TI  - The role of PTEN/Akt/PI3K signaling in the maintenance and viability of prostate
      cancer stem-like cell populations.
AB  - Characterization of the molecular pathways that are required for the viability
      and maintenance of self-renewing tumor-initiating cells may ultimately lead to
      improved therapies for cancer. In this study, we show that a CD133(+)/CD44(+)
      population of cells enriched in prostate cancer progenitors (PCaPs) has tumor
      initiating potential and that these progenitors can be expanded under
      nonadherent, serum-free, sphere-forming conditions. Cells grown under these
      conditions have increased in vitro clonogenic and in vivo tumorigenic potential.
      mRNA expression analysis of cells grown under sphere-forming conditions, compared
      with long-term monolayer cultures, revealed preferential activation of the
      PI3K/AKT signaling pathway. PI3K p110alpha and beta-protein levels were higher in
      cells grown under sphere-forming conditions, and phosphatase and tensin homolog
      (PTEN) knockdown by shRNA led to an increase in sphere formation as well as
      increased clonogenic and tumorigenic potential. Similarly, shRNA knockdown of
      FoxO3a led to an increase in tumorigenic potential. Consistent with these
      results, inhibition of PI3K activity by the dual PI3K/mTOR inhibitor NVP-BEZ235
      led to growth inhibition of PCaPs. Taken together, our data strongly suggest that
      the PTEN/PI3K/Akt pathways are critical for prostate cancer stem-like cell
      maintenance and that targeting PI3K signaling may be beneficial in prostate
      cancer treatment by eliminating prostate cancer stem-like cells.

PMID- 19116270
TI  - Identification of direct residue contacts in protein-protein interaction by
      message passing.
AB  - Understanding the molecular determinants of specificity in protein-protein
      interaction is an outstanding challenge of postgenome biology. The availability
      of large protein databases generated from sequences of hundreds of bacterial
      genomes enables various statistical approaches to this problem. In this context
      covariance-based methods have been used to identify correlation between amino
      acid positions in interacting proteins. However, these methods have an important
      shortcoming, in that they cannot distinguish between directly and indirectly
      correlated residues. We developed a method that combines covariance analysis with
      global inference analysis, adopted from use in statistical physics. Applied to a
      set of >2,500 representatives of the bacterial two-component signal transduction
      system, the combination of covariance with global inference successfully and
      robustly identified residue pairs that are proximal in space without resorting to
      ad hoc tuning parameters, both for heterointeractions between sensor kinase (SK)
      and response regulator (RR) proteins and for homointeractions between RR
      proteins. The spectacular success of this approach illustrates the effectiveness
      of the global inference approach in identifying direct interaction based on
      sequence information alone. We expect this method to be applicable soon to
      interaction surfaces between proteins present in only 1 copy per genome as the
      number of sequenced genomes continues to expand. Use of this method could
      significantly increase the potential targets for therapeutic intervention, shed
      light on the mechanism of protein-protein interaction, and establish the
      foundation for the accurate prediction of interacting protein partners.

PMID- 19116271
TI  - Wnt signaling targets ETO coactivation domain of TAF4/TFIID in vivo.
AB  - Understanding the diverse activities of the multisubunit core promoter
      recognition complex TFIID in vivo requires knowledge of how individual subunits
      contribute to overall functions of this TATA box-binding protein (TBP)/TBP
      associated factor (TAF) complex. By generating altered holo-TFIID complexes in
      Drosophila we identify the ETO domain of TAF4 as a coactivator domain likely
      targeted by Pygopus, a protein that is required for Wingless-induced
      transcription of naked cuticle. These results establish a coactivator function of
      TAF4 and provide a strategy to dissect mechanisms of TFIID function in vivo.

PMID- 19116272
TI  - Expression levels of a filament-specific transcriptional regulator are sufficient
      to determine Candida albicans morphology and virulence.
AB  - Candida albicans, the major human fungal pathogen, undergoes a reversible
      morphological transition from single yeast cells to pseudohyphal and hyphal
      filaments (elongated cells attached end-to-end). Because typical C. albicans
      infections contain a mixture of these morphologies it has, for many years, been
      difficult to assess the relative contribution of each form to virulence. In
      addition, the regulatory mechanisms that determine growth in pseudohyphal and
      hyphal morphologies are largely unknown. To address these questions we have
      generated a C. albicans strain that can be genetically manipulated to grow
      completely in the hyphal form under non-filament-inducing conditions in vitro.
      This was achieved by inducing high-level constitutive expression of UME6, a
      recently identified filament-specific transcriptional regulator of C. albicans
      hyphal extension. We show that high-level UME6 expression significantly increases
      hyphal formation and promotes virulence in a mouse model of systemic candidiasis.
      Our results strongly suggest that shifting the morphology of a C. albicans
      population toward the hyphal form, and/or increasing hyphal-specific gene
      expression, during the course of infection is sufficient to improve virulence
      potential. We also demonstrate that lower levels of UME6 expression specify
      growth largely in the pseudohyphal form and that increasing UME6 levels is
      sufficient to cause cells to gradually shift from pseudohyphal to hyphal
      morphology. In addition, we show that UME6 levels differentially induce the
      expression of several known filament-specific transcripts. These findings suggest
      that a common transcriptional regulatory mechanism functions to specify both
      pseudohyphal and hyphal morphologies in a dosage-dependent manner.

PMID- 19116274
TI  - The key role of the surface membrane in why gastropod nacre grows in towers.
AB  - The nacre of gastropod molluscs is intriguingly stacked in towers. It is covered
      by a surface membrane, which protects the growing nacre surface from damage when
      the animal withdraws into its shell. The surface membrane is supplied by vesicles
      that adhere to it on its mantle side and secretes interlamellar membranes from
      the nacre side. Nacre tablets rapidly grow in height and later expand sideways;
      the part of the tablet formed during this initial growth phase is here called the
      core. During initial growth, the tips of the cores remain permanently submerged
      within the surface membrane. The interlamellar membranes, which otherwise
      separate the nacre tablet lamellae, do not extend across cores, which are aligned
      in stacked tablets forming the tower axis, and thus towers of nacre tablets are
      continuous along the central axis. We hypothesize that in gastropod nacre growth
      core formation precedes that of the interlamellar membrane. Once the core is
      complete, a new interlamellar membrane, which covers the area of the tablet
      outside the core, detaches from the surface membrane. In this way, the tower-like
      growth of gastropod nacre becomes comprehensible.

PMID- 19116273
TI  - Activated protein C ligation of ApoER2 (LRP8) causes Dab1-dependent signaling in
      U937 cells.
AB  - Binding of activated protein C (APC) to cells triggers multiple beneficial
      cytoprotective activities that suppress apoptosis, inflammation, and endothelial
      barrier breakdown. One paradigm for APC's signaling emphasizes its binding to
      endothelial cell protein C receptor (EPCR) and subsequent protease activated
      receptor (PAR)-1 activation. Here we used human monocytic-like U937 cells to
      evaluate apolipoprotein E receptor 2 (ApoER2)-dependent signaling by APC and
      found that APC initiated rapid phosphorylation of Tyr-220 in the adaptor protein
      disabled-1 (Dab1) and of Ser-473 in Akt. APC also induced phosphorylation of Ser
      9 in glycogen synthase kinase 3beta (GSK3beta), which was blocked by the PI3K
      inhibitor LY294002. Receptor-associated protein (RAP), a general antagonist for
      binding of ligands to LDL receptor family members, inhibited APC-induced
      phosphorylation of Dab1 and GSK3beta, whereas anti-EPCR or anti-PAR1 blocking
      antibodies did not. Knocking down ApoER2 by using siRNA-ablated APC induced Dab1
      phosphorylation, suggesting that RAP-sensitive APC-induced signaling requires
      ApoER2. In surface plasmon resonance equilibrium binding studies, APC bound with
      high affinity to soluble (s) ApoER2 (apparent K(d), approximately 30 nM) but not
      to soluble very low density lipoprotein receptor. RAP blocked APC binding to
      sApoER2 but not to sEPCR. RAP blocked binding of U937 cells to immobilized APC.
      RAP also blocked APC's ability to inhibit endotoxin-induced tissue factor pro
      coagulant activity of U937 cells. Thus, we propose that ligation of ApoER2 by APC
      signals via Dab1 phosphorylation and subsequent activation of PI3K and Akt and
      inactivation of GSK3beta, thereby contributing to APC's beneficial effects on
      cells.

PMID- 19116275
TI  - Contrasted patterns of hyperdiversification in Mediterranean hotspots.
AB  - Dating the Tree of Life has now become central to relating patterns of
      biodiversity to key processes in Earth history such as plate tectonics and
      climate change. Regions with a Mediterranean climate have long been noted for
      their exceptional species richness and high endemism. How and when these biota
      assembled can only be answered with a good understanding of the sequence of
      divergence times for each of their components. A critical aspect of dating by
      using molecular sequence divergence is the incorporation of multiple suitable age
      constraints. Here, we show that only rigorous phylogenetic analysis of fossil
      taxa can lead to solid calibration and, in turn, stable age estimates, regardless
      of which of 3 relaxed clock-dating methods is used. We find that Proteaceae, a
      model plant group for the Mediterranean hotspots of the Southern Hemisphere with
      a very rich pollen fossil record, diversified under higher rates in the Cape
      Floristic Region and Southwest Australia than in any other area of their total
      distribution. Our results highlight key differences between Mediterranean
      hotspots and indicate that Southwest Australian biota are the most
      phylogenetically diverse but include numerous lineages with low diversification
      rates.

PMID- 19116276
TI  - Synaptic activity-responsive element in the Arc/Arg3.1 promoter essential for
      synapse-to-nucleus signaling in activated neurons.
AB  - The neuronal immediate early gene Arc/Arg-3.1 is widely used as one of the most
      reliable molecular markers for intense synaptic activity in vivo. However, the
      cis-acting elements responsible for such stringent activity dependence have not
      been firmly identified. Here we combined luciferase reporter assays in cultured
      cortical neurons and comparative genome mapping to identify the critical synaptic
      activity-responsive elements (SARE) of the Arc/Arg-3.1 gene. A major SARE was
      found as a unique approximately 100-bp element located at >5 kb upstream of the
      Arc/Arg-3.1 transcription initiation site in the mouse genome. This single
      element, when positioned immediately upstream of a minimal promoter, was
      necessary and sufficient to replicate crucial properties of endogenous Arc/Arg
      3.1's transcriptional regulation, including rapid onset of transcription
      triggered by synaptic activity and low basal expression during synaptic
      inactivity. We identified the major determinants of SARE as a unique cluster of
      neuronal activity-dependent cis-regulatory elements consisting of closely
      localized binding sites for CREB, MEF2, and SRF. Consistently, a SARE reporter
      could readily trace and mark an ensemble of cells that have experienced intense
      activity in the recent past in vivo. Taken together, our work uncovers a novel
      transcriptional mechanism by which a critical 100-bp element, SARE, mediates a
      predominant component of the synapse-to-nucleus signaling in ensembles of Arc/Arg
      3.1-positive activated neurons.

PMID- 19116278
TI  - The use of amphipols as universal molecular adapters to immobilize membrane
      proteins onto solid supports.
AB  - Because of the importance of their physiological functions, cell membranes
      represent critical targets in biological research. Membrane proteins, which make
      up approximately 1/3 of the proteome, interact with a wide range of small ligands
      and macromolecular partners as well as with foreign molecules such as synthetic
      drugs, antibodies, toxins, or surface recognition proteins of pathogenic
      organisms. Whether it is for the sake of basic biomedical or pharmacological
      research, it is of great interest to develop tools facilitating the study of
      these interactions. Surface-based in vitro assays are appealing because they
      require minimum quantities of reagents, and they are suitable for multiplexing
      and high-throughput screening. We introduce here a general method for
      immobilizing functional, unmodified integral membrane proteins onto solid
      supports, thanks to amphipathic polymers called "amphipols." The key point of
      this approach is that functionalized amphipols can be used as universal adapters
      to associate any membrane protein to virtually any kind of support while
      stabilizing its native state. The generality and versatility of this strategy is
      demonstrated by using 5 different target proteins, 2 types of supports (chips and
      beads), 2 types of ligands (antibodies and a snake toxin), and 2 detection
      methods (surface plasmon resonance and fluorescence microscopy).

PMID- 19116277
TI  - Scaffold-based discovery of indeglitazar, a PPAR pan-active anti-diabetic agent.
AB  - In a search for more effective anti-diabetic treatment, we used a process
      coupling low-affinity biochemical screening with high-throughput co
      crystallography in the design of a series of compounds that selectively modulate
      the activities of all three peroxisome proliferator-activated receptors (PPARs),
      PPARalpha, PPARgamma, and PPARdelta. Transcriptional transactivation assays were
      used to select compounds from this chemical series with a bias toward partial
      agonism toward PPARgamma, to circumvent the clinically observed side effects of
      full PPARgamma agonists. Co-crystallographic characterization of the lead
      molecule, indeglitazar, in complex with each of the 3 PPARs revealed the
      structural basis for its PPAR pan-activity and its partial agonistic response
      toward PPARgamma. Compared with full PPARgamma-agonists, indeglitazar is less
      potent in promoting adipocyte differentiation and only partially effective in
      stimulating adiponectin gene expression. Evaluation of the compound in vivo
      confirmed the reduced adiponectin response in animal models of obesity and
      diabetes while revealing strong beneficial effects on glucose, triglycerides,
      cholesterol, body weight, and other metabolic parameters. Indeglitazar has now
      progressed to Phase II clinical evaluations for Type 2 diabetes mellitus (T2DM).

PMID- 19116279
TI  - Sic1-induced DNA rereplication during meiosis.
AB  - Orderly progression through meiosis requires strict regulation of DNA metabolic
      events, so that a single round of DNA replication is systematically followed by a
      recombination phase and 2 rounds of chromosome segregation. We report here the
      disruption of this sequence of events in Saccharomyces cerevisiae through meiosis
      specific induction of the cyclin-dependent kinase (CDK) inhibitor Sic1 mutated at
      multiple phosphorylation sites. Accumulation of this stabilized version of Sic1
      led to significant DNA rereplication in the absence of normal chromosome
      segregation. Deletion of DMC1 abolished DNA rereplication, but additional
      deletion of RAD17 restored the original phenotype. Therefore, activation of the
      meiotic recombination checkpoint, which arrests meiotic progression at pachytene,
      suppressed DNA rereplication resulting from Sic1 stabilization. In contrast to
      deletion of DMC1, deletion of NDT80, which encodes a transcription factor
      required for pachytene exit, did not inhibit DNA rereplication. Our results
      provide strong evidence that CDK activity is required to prevent inappropriate
      initiation of DNA synthesis before the meiotic divisions.

PMID- 19116280
TI  - Genome rhetoric and the emergence of compositional bias.
AB  - Genomes exhibit diverse patterns of species-specific GC content, GC and AT skews,
      codon bias, and mutation bias. Despite intensive investigations and the rapid
      accumulation of sequence data, the causes of these a priori different genome
      biases have not been agreed on and seem multifactorial and idiosyncratic. We show
      that these biases can arise generically from an instability of the coevolutionary
      dynamics between genome composition and resource allocation for translation,
      transcription, and replication. Thus, we offer a unifying framework for
      understanding and analyzing different genome biases. We develop a test of
      multistability of nucleotide composition of completely sequenced genomes and
      reveal a bistability for Borrelia burgdorferi, a genome with pronounced
      replication-related biases. These results indicate that evolution generates
      rhetoric, it improves the efficiency of the genome's communication with the cell
      without modifying the message, and this leads to bias.

PMID- 19116281
TI  - Condensation of FtsZ filaments can drive bacterial cell division.
AB  - Forces are important in biological systems for accomplishing key cell functions,
      such as motility, organelle transport, and cell division. Currently, known force
      generation mechanisms typically involve motor proteins. In bacterial cells, no
      known motor proteins are involved in cell division. Instead, a division ring (Z
      ring) consists of mostly FtsZ, FtsA, and ZipA is used to exerting a contractile
      force. The mechanism of force generation in bacterial cell division is unknown.
      Using computational modeling, we show that Z-ring formation results from the
      colocalization of FtsZ and FtsA mediated by the favorable alignment of FtsZ
      polymers. The model predicts that the Z-ring undergoes a condensation transition
      from a low-density state to a high-density state and generates a sufficient
      contractile force to achieve division. FtsZ GTP hydrolysis facilitates monomer
      turnover during the condensation transition, but does not directly generate
      forces. In vivo fluorescence measurements show that FtsZ density increases during
      division, in accord with model results. The mechanism is akin to van der Waals
      picture of gas-liquid condensation, and shows that organisms can exploit
      microphase transitions to generate mechanical forces.

PMID- 19116282
TI  - Passive transport across bilayer lipid membranes: Overton continues to rule.

PMID- 19116283
TI  - Origins of replication in Cyanothece 51142.

PMID- 19116284
TI  - A fortuitous insight into a common mode of RNA recognition by the dsRNA-specific
      zinc fingers.

PMID- 19116286
TI  - Can the FMR1 (fragile X) gene serve as predictor of response to ovarian
      stimulation?
AB  - Because triple CGG repeats on FMR1 correlate with anti-Mullerian hormone, repeats
      may also correlate with clinical outcomes. In 55 in vitro fertilization patients,
      repeats, corrected for gonadotropin dosage, were, therefore, correlated to
      oocytes. Patients were stratified by <35 and > or =35 repeats, and by age to <38
      or > or =38 years. Less than 35 (but not > or =35) repeats demonstrated
      significantly lower anti-Mullerian hormone at ages > or =38 than at <38 years ( P
      < .05). In >38 years, anti-Mullerian hormone was not affected by repeats. In <38
      years, with <35 repeats (though not with > or =35), required significantly less
      gonadotropins than > or =38 ( P < .05). In <38 years (though not > or =38), those
      with <35 repeats produced significantly more oocytes than women with > or =35
      repeats ( P = .006). In <38 years, retrieved oocytes were inversely related to
      repeats, adjusted for gonadotropin dosage ( P = .03). This supports FMR1 testing
      as useful in fertility practice and suggests why response rates to increasing
      stimulation with gonadotropins may vary.

PMID- 19116287
TI  - Soft-hydrothermal processing of red cedar bedding reduces its induction of
      cytochrome P450 in mouse liver.
AB  - Red cedar-derived bedding materials cause changes in cytochrome P450-dependent
      microsomal enzyme systems in laboratory animals. We examined the effect of
      essential oil of red cedar (EORC), as well as the effect of bedding from which it
      had been removed, on the hepatic expression cytochrome P450s in mice. EORC was
      obtained from liquid extracts of red cedar bedding by a soft-hydrothermal process
      and was administered orally to mice. Between days 1 and 2 after administration,
      hepatic P450s were significantly induced as follows: CYP3As, 7.1x; CYP1As, 1.6x;
      CYP2E1, 1.5x; CYP2Cs, 1.6x. A housing study of mice indicated that red cedar
      bedding increased the levels of these P450s in mouse liver, whereas mice housed
      in cedar bedding from which EORC had been removed (ST-cedar bedding) showed
      significantly lower levels of P450s, especially CYP3As, CYP1As and CYP2E1. Soft
      hydrothermal processing partially removed many components of EORC. In particular,
      several volatile sesquiterpenes, naphthalene-derived aromatics and 4,4-dimethyl
      13alpha-androst-5-ene were decreased in the ST-cedar bedding, suggesting that
      these may be responsible for P450 induction. This study demonstrated that the
      removal of these volatile compounds by soft-hydrothermal processing can decrease
      the hepatic P450-inducing effect of red cedar bedding.

PMID- 19116288
TI  - Clostridial typhlitis associated with topical antibiotic therapy in a Syrian
      hamster.
AB  - A Syrian hamster that had been treated with topical antibiotic ointment for 10
      days following injuries sustained during fighting was presented moribund.
      Postmortem and microscopic examinations revealed lesions consistent with
      clostridial typhlitis and enteritis. Anaerobic culture of caecal contents
      resulted in the isolation of two Clostridium species, and caecal contents
      contained Clostridium difficile enterotoxins. Based on these findings, a
      diagnosis of acute C. difficile enterotoxaemia was made. This report discusses
      the pathogenesis of C. difficile enterotoxaemia and the potential role of topical
      antibiotic ointment therapy in initiating the disease.

PMID- 19116289
TI  - The effect of defect localization on spontaneous repair of osteochondral defects
      in a Gottingen minipig model: a retrospective analysis of the medial patellar
      groove versus the medial femoral condyle.
AB  - Various animal models for experimental osteochondral defect healing have been
      used in orthopaedic research. Two main defect locations were chosen: the patellar
      groove or the central part of the medial femoral condyles (MFC). To date, it is
      not clear whether both locations display similar patterns in critical size
      osteochondral defect healing. We retrospectively analysed both locations in our
      minipig model hypothesizing that they show similar healing pattern. Thirty-five
      defects were analysed after three or 12 months. Osteochondral defects were 10 mm
      deep and 6.3 mm (MFC, n = 19) in diameter or 8 mm and 5.4 mm, respectively
      (trochlear groove [TG], n = 16). Semi-quantitative histological scoring and
      histomorphological evaluation were carried out. Both defect locations showed
      fillings of fibrous and fibrocartilage-like repair tissue. The osseous defect was
      closed by endochondral bone formation in the MFC. Semi-quantitative scoring did
      not show differences, whereas qualitative histomorphological analysis more
      frequently showed cartilaginous repair tissue in MFC defects. There was more
      frequent subchondral bone cyst formation in MFC location (P = 0.05), TG defects
      resulted in lower postoperative pain. Both defect localizations are suitable for
      studies on osteochondral healing. Since regenerating with less hyaline-like
      repair tissue and less subchondral cyst formation, TG is more favourable for
      experimental osteochondral defect healing in this model.

PMID- 19116290
TI  - An in vivo magnetic resonance imaging technique for measurement of rat lumbar
      vertebral body blood perfusion.
AB  - The technical feasibility of dynamic contrast-enhanced magnetic resonance imaging
      (MRI) measurement of rat vertebral blood perfusion using a 1.5 T clinical scanner
      and a small surface coil was investigated in this study. Nine male 7-month-old
      Wistar-Kyoto rats were used. Computed tomographic assessment of lumbar vertebral
      bone mineral density (BMD) and MRI assessment of lumbar vertebral blood perfusion
      were performed twice with 8 weeks' interval. A 4.7 cm surface coil was used for
      receiving radiofrequency signal. Gadolinium-DOTA (0.3 mmol/kg) was injected
      through the tail vein of the rat as a quick bolus and dynamic MRI scan was
      carried out on the central sagittal plane of the lumbar spine for 8 min with a
      temporal resolution of 0.6 s. Blood perfusion parameters of wash-in rate, maximum
      enhancement and wash-out rate were derived from the dynamic MR images. No
      vertebral body size and vertebral BMD difference was detected between the two
      time points (P=0.222 and 0.123, respectively). Wash-in rate was 0.105 (+/-0.016)%
      and 0.111 (+/-0.018)%, maximum enhancement 126.5 (+/-10.6)% and 129.2 (+/-13.4)%,
      and wash-out rate 0.788 (+/-0.182)% and 0.792 (+/-0.182)% for the two time
      points. With these parameters, no difference was found between the two time
      points with a P value of 0.575, 0.889 and 0.754, respectively. We conclude that
      dynamic contrast-enhanced MRI measurement of rat vertebral blood perfusion using
      a 1.5 T clinical scanner and a small surface coil is feasible and reliable. This
      technique offers a non-invasive means to probe vertebral blood perfusion changes
      associated with rat disease models.

PMID- 19116291
TI  - Longitudinal as well as age-matched assessments of bone changes in the mature
      ovariectomized rat model.
AB  - In the past, bone loss in the ovariectomized (OVX) osteoporotic rat model has
      been monitored using in vitro micro-computed tomography (micro-CT) to assess bone
      structure (bone volume/total volume, BV/TV). The purpose of this study was to
      assess the importance of baseline control and sham groups in 12-16-week-old,
      reproductively mature rats. Measurements were carried out in a longitudinal and
      age-matched fashion using newer in vivo peripheral quantitative computed
      tomography (pQCT), which measures apparent bone mineral density (BMD). BMD was
      measured at the distal femoral metaphysis of 12-week-old female Wistar rats with
      pQCT. Subsequently, animals were either OVX or sham operated, and pQCT
      measurements were repeated four weeks later. Then, all rats were euthanized and
      in vitro BMD and BV/TV were obtained by micro-CT imaging. Results from three
      consistently differentiated regions of interest showed that there was significant
      bone loss and growth during the four weeks in the OVX and sham group,
      respectively. Taking this into account, i.e. a posteriori superimposing growth to
      loss, no differences resulted between BMD values measured in a longitudinal
      fashion with pQCT and that measured in comparison with an age-matched sham group
      with micro-CT and pQCT. In addition, there was a strong linear correlation
      between BMD measured with pQCT and BV/TV obtained from micro-CT. In conclusion,
      this outcome provides new insights into individual bone changes due to OVX and
      growth in Wistar rats during the age period of 12-16 weeks, which is often
      applied in osteoporosis research as the 'mature' rat model. Data can be used as
      baseline information upon which future in vivo study designs with this rat model
      can refer to reduce and minimize animal use.

PMID- 19116292
TI  - Experimental middle ear surgery in rabbits: a new approach for reconstructing the
      ossicular chain.
AB  - This experimental animal study aimed at evaluating a new prosthesis to replace
      the ossicular chain; we developed a new technique for surgical implantation into
      the middle ear of rabbits. The rabbit middle ear is, owing to the relative
      anatomical dimensions involved, an ideal environment for implantation procedures
      involving the ossicles, as the surgical conditions are similar to those of the
      human middle ear. This study included a total of 34 approximately six-month-old
      female white rabbits (New Zealand) weighing between 3.2 and 4.4 kg. The implants
      used were constructed of ceramic materials (titania, TiO(2)) of various pore
      sizes. Directly prior to implanting the total ossicular reconstruction prostheses
      (TORPs), as well as at 28, 84 and 300 days after implantation, electric response
      audiometry was used to determine the hearing thresholds of the animals (bone
      conduction; click stimulus nHL). An erbium:YAG laser was used to excise the
      original ossicular chain. Following implantation, we were unable to detect any
      stenosis of the outer ear canal or perforation of the tympanic membrane. The
      conductive hearing threshold was in the range of 4.21 +/- 6.68 dB nHL (n = 131).
      The hearing level showed no significant difference before and after surgery (P <
      0.05).

PMID- 19116293
TI  - A review of the need and possible uses for genetically standardized Atlantic
      salmon (Salmo salar) in research.
AB  - Large numbers of Atlantic salmon (Salmo salar) are used as research animals in
      basic research and to solve challenges related to the fish-farming industry. Most
      of this research is performed on farmed animals provided by local breeders or
      national breeding companies. The genetic constitution of these animals is usually
      unknown and highly variable. As a result, large numbers of fish are often needed
      to produce significant results, and results from one study are often impossible
      to reproduce in another facility. The production of standardized salmon could in
      many cases reduce the number of animals used in research and at the same time
      provide more reproducible results. This paper provides an overview of the methods
      available for the production of standardized Atlantic salmon, and discusses the
      pros and cons of each technique. The use of zebrafish and other well-defined
      laboratory fish species as a model for salmon is also discussed. Access to
      genetically defined fish would greatly benefit the scientific community, in the
      same way as genetically defined lines of rodents have revolutionized mammalian
      research.

PMID- 19116294
TI  - Reported analgesic administration to rabbits, pigs, sheep, dogs and non-human
      primates undergoing experimental surgical procedures.
AB  - Reported analgesic use following experimental surgery is low in rodents and there
      has been little published information on the frequency of analgesic use in other
      laboratory species. A structured literature review was conducted to examine
      analgesic administration in larger laboratory animals. The Scirus search engine
      was used to identify studies published in peer-reviewed journals that reported
      carrying out experimental surgery on 'large' laboratory animals, specifically
      rabbits, pigs, sheep, dogs and non-human primates. Seventy-four studies between
      2000 and 2001 and 75 studies between 2005 and 2006 were included in the review.
      There was an increase in the reported administration of systemic analgesics to
      these species from 50% in 2000-2001 to 63% in 2005-2006. When all agents with
      analgesic properties were considered (systemic analgesics, local anaesthetics and
      anaesthetics with analgesic components), the proportion of papers that reported
      some form of analgesic administration to 'large' laboratory animals increased
      from 86% in 2000-2001 to 89% in 2005-2006. Overall rabbits, pigs, sheep, dogs and
      non-human primates were more likely to receive analgesics following potentially
      painful experimental procedures than has been reported in laboratory rodents but
      analgesic administration to 'large' laboratory species is still not optimal.

PMID- 19116295
TI  - Reducing variation in a rabbit vaccine safety study with particular emphasis on
      housing conditions and handling.
AB  - This paper describes the results of a study of the effects of modified housing
      conditions, conditioning and habituation on humans using a rabbit model for
      monitoring whole-cell pertussis vaccine (pWCV)-induced adverse effects. The study
      has been performed with reference to previous vaccine safety studies of pWCV in
      rabbits in which results were difficult to interpret due to the large variation
      in experimental outcome, especially in the key parameter deep-body temperature
      (T(b)). Certain stressful laboratory conditions, as well as procedures involving
      humans, e.g. blood sampling, inoculation and cage-cleaning, were hypothesized to
      cause this large variation. The results of this study show that under modified
      housing conditions rabbits have normal circadian body temperatures. This allowed
      discrimination of pWCV-induced adverse effects in which handled rabbits tended to
      show a dose-related increase in temperature after inoculation with little
      variance, whereas non-handled rabbits did not. Effects of experimental and
      routine procedures on body temperature were significantly reduced under modified
      conditions and were within the normal T(b) range. Handled animals reacted less
      strongly and with less variance to experimental procedures, such as blood
      sampling, injection and cage-cleaning, than non-handled rabbits. Overall,
      handling had a positive effect on the behaviour of the animals. Data show that
      the housing modifications have provided a more robust model for monitoring pWCV
      adverse effects. Furthermore, conditioning and habituation of rabbits to humans
      reduce the variation in experimental outcome, which might allow for a reduction
      in the number of animals used. In addition, this also reduces distress and thus
      contributes to refining this animal model.

PMID- 19116296
TI  - A new method for induction and synchronization of oestrus and fertile ovulations
      in mice by using exogenous hormones.
AB  - Four consecutive experiments were conducted to design and establish the
      effectiveness of different protocols for induction and synchronization of oestrus
      and ovulation in mice. Results showed that the highest synchronization degree and
      the highest fertility rates were obtained using two intraperitoneal doses of 0.5
      microg of cloprostenol, three days apart, plus a single subcutaneous dose of 3
      microg of progesterone coincidentally with the first injection of cloprostenol.
      Of the main advantages of the new method, we have to highlight the short time
      elapsed for appearance, and the high degree of synchronization of oestrus and
      ovulations (almost 100% of the animals responding to the treatment in 48 h; 78.4%
      with fertile mates at 24 h), plus the high fertility rate obtained after a
      programmed mating (100%). Overall, these yields are superior to those obtained by
      classical methods based on the use of male pheromones; hence the proposed
      protocol arises as an adequate alternative for reproductive management in mice.

PMID- 19116297
TI  - Reported analgesic and anaesthetic administration to rodents undergoing
      experimental surgical procedures.
AB  - A structured literature review was carried out to assess recent trends in the
      administration of analgesics and anaesthetics to laboratory rats and mice
      undergoing surgical procedures. The ScienceDirect database was used to
      systematically identify studies published in peer-reviewed journals over two
      periods (2000-2001 and 2005-2006), 86 studies from each time period were included
      in the review. The total number of animals that underwent surgery, species used,
      type of procedure, anaesthetic regimen and analgesic administration were noted
      for each study. There was an increase in the reported administration of systemic
      analgesics from 10% in 2000-2001 to 20% in 2005-2006. Buprenorphine was the most
      commonly reported analgesic in both periods (2000-2001: 78%, 2005-2006: 35%) and
      reporting the use of non-steroidal anti-inflammatory drugs increased from 11% to
      53%. There was also a change in reported anaesthetic practices, notably a
      decrease in the use of pentobarbital and an increase in the use of isoflurane and
      ketamine/xylazine. Although reported administration of analgesics has increased
      and there has been some refinement in the selection of anaesthetic agents used,
      the findings of this review suggest that there is still significant scope for
      improvement with respect to the perioperative care of laboratory rodents.

PMID- 19116298
TI  - A new small animal model for the study of spine fusion in the sand rat: pilot
      studies.
AB  - Spine fusion is used to treat traumatic or degenerative lumbar instability in the
      cervical or lumbar spine. Although degenerative radiological changes in discs
      adjacent to a fusion have been well-recognized, histopathological changes in
      adjacent discs have not been studied and are poorly understood. An economical
      small animal model for lumbar fusion would be a useful research tool. Study
      objectives were to: (1) develop a model of non-instrumented spine fusion in the
      sand rat, a rodent with spontaneous, age-related disc degeneration; (2) use
      radiological-histological analyses to study fusion and disc degeneration in
      cranial and caudal discs adjacent to the fusion. Studies were approved by our
      Institutional Animal Care and Use Committee. A small segment of outer annulus
      tissue was surgically removed from lumbar discs, radiographs obtained and the
      animal allowed to recover and age. At surgical harvest, radiographs of 28 spine
      fusion specimens were scored and statistically analysed for adjacent disc space
      narrowing, wedging, endplate sclerosis and irregular disc margins. At harvest,
      the incidence of these radiological indices of disc degeneration were
      significantly greater than at time of surgery. Pilot studies presented here
      indicate that this model provides a novel addition to basic science approaches
      studying the clinically important topic of spinal fusion and adjacent segment
      changes. The resulting fusion site can be assessed statistically with
      radiological scoring to determine development/progression of disc degeneration in
      adjacent segments, and correlative histological features can be examined. The
      sand rat is well-suited for use in spine fusion studies because of
      reliable/reproducible progression of disc degeneration and the favourable
      economics of small rodent studies.

PMID- 19116299
TI  - Current concepts in Alzheimer's disease: a multidisciplinary review.
AB  - This comprehensive, pedagogically-oriented review is aimed at a heterogeneous
      audience representative of the allied disciplines involved in research and
      patient care. After a foreword on epidemiology, genetics, and risk factors, the
      amyloid cascade model is introduced and the main neuropathological hallmarks are
      discussed. The progression of memory, language, visual processing, executive,
      attentional, and praxis deficits, and of behavioral symptoms is presented. After
      a summary on neuropsychological assessment, emerging biomarkers from
      cerebrospinal fluid assays, magnetic resonance imaging, nuclear medicine, and
      electrophysiology are discussed. Existing treatments are briefly reviewed,
      followed by an introduction to emerging disease-modifying therapies such as
      secretase modulators, inhibitors of Abeta aggregation, immunotherapy, inhibitors
      of tau protein phosphorylation, and delivery of nerve growth factor.

PMID- 19116300
TI  - Neural stem cells and Alzheimer's disease: challenges and hope.
AB  - Alzheimer's disease is characterized by degeneration and dysfunction of synapses
      and neurons in brain regions critical for learning and memory functions. The
      endogenous generation of new neurons in certain regions of the mature brain,
      derived from primitive cells termed neural stem cells, has raised hope that
      neural stem cells may be recruited for structural brain repair. Stem cell therapy
      has been suggested as a possible strategy for replacing damaged circuitry and
      restoring learning and memory abilities in patients with Alzheimer's disease. In
      this review, we outline the promising investigations that are raising hope, and
      understanding the challenges behind translating underlying stem cell biology into
      novel clinical therapeutic potential in Alzheimer's disease.

PMID- 19116301
TI  - A review of telephone-administered screening tests for dementia diagnosis.
AB  - Dementia screening measures serve an important role in epidemiological research,
      clinical trials, identifying patients for more comprehensive assessment, and
      monitoring progression. Telephone-administered measures allow increased
      flexibility. Although there are several extant telephone-administered measures
      that offer the promise of efficient detection of cognitive impairment, research
      evidence supporting their use is limited. We review telephone-based cognitive
      screening instruments for detecting dementia or mild cognitive impairment,
      critically review the evidence for their validity, and make recommendations for
      future research directions. Most measures reviewed do a good job of classifying
      patients as likely to have dementia or likely to be neurologically healthy.
      However, with sensitivity values ranging from 38% to 100% and specificity values
      ranging from 79% to 100%, there is considerable variability in the measures
      available. Future validation studies should reflect the populations most likely
      to benefit from a telephone-based measure, namely community-dwelling elderly who
      have not yet been identified as being cognitively impaired. 

PMID- 19116302
TI  - Assessing caregivers for team interventions (ACT): a new paradigm for
      comprehensive hospice quality care.
AB  - This article provides a framework labeled ACT that aims to successfully integrate
      family caregivers and patients into one unit of care, as dictated by the hospice
      philosophy. ACT (assessing caregivers for team interventions) is based on the
      ongoing assessment of the caregiver background context, primary, secondary, and
      intrapsychic stressors as well as outcomes of the caregiving experience and
      subsequently, the design and delivery of appropriate interventions to be
      delivered by the hospice interdisciplinary team. Interventions have to be
      tailored to a caregiver's individual needs; such a comprehensive needs assessment
      allows teams to customize interventions recognizing that most needs and
      challenges cannot be met by only one health care professional or only one
      discipline. The proposed model ensures a holistic approach to address the
      multifaceted challenges of the caregiving experience.

PMID- 19116303
TI  - Prediction of merozoite surface protein 1 and apical membrane antigen 1 vaccine
      efficacies against Plasmodium chabaudi malaria based on prechallenge antibody
      responses.
AB  - For the development of blood-stage malaria vaccines, there is a clear need to
      establish in vitro measures of the antibody-mediated and the cell-mediated immune
      responses that correlate with protection. In this study, we focused on
      establishing correlates of antibody-mediated immunity induced by immunization
      with apical membrane antigen 1 (AMA1) and merozoite surface protein 1(42)
      (MSP1(42)) subunit vaccines. To do so, we exploited the Plasmodium chabaudi
      rodent model, with which we can immunize animals with both protective and
      nonprotective vaccine formulations and allow the parasitemia in the challenged
      animals to peak. Vaccine formulations were varied with regard to the antigen
      dose, the antigen conformation, and the adjuvant used. Prechallenge antibody
      responses were evaluated by enzyme-linked immunosorbent assay and were tested for
      a correlation with protection against nonlethal P. chabaudi malaria, as measured
      by a reduction in the peak level of parasitemia. The analysis showed that neither
      the isotype profile nor the avidity of vaccine-induced antibodies correlated with
      protective efficacy. However, high titers of antibodies directed against
      conformation-independent epitopes were associated with poor vaccine performance
      and may limit the effectiveness of protective antibodies that recognize
      conformation-dependent epitopes. We were able to predict the efficacies of the P.
      chabaudi AMA1 (PcAMA1) and P. chabaudi MSP1(42) (PcMSP1(42)) vaccines only when
      the prechallenge antibody titers to both refolded and reduced/alkylated antigens
      were considered in combination. The relative importance of these two measures of
      vaccine-induced responses as predictors of protection differed somewhat for the
      PcAMA1 and the PcMSP1(42) vaccines, a finding confirmed in our final immunization
      and challenge study. A similar approach to the evaluation of vaccine-induced
      antibody responses may be useful during clinical trials of Plasmodium falciparum
      AMA1 and MSP1(42) vaccines.

PMID- 19116304
TI  - Acute parvovirus B19 infection frequently causes false-positive results in
      Epstein-Barr virus- and herpes simplex virus-specific immunoglobulin M
      determinations done on the Liaison platform.
AB  - During an outbreak of parvovirus B19 we collected serum samples from 68
      nonpregnant patients in the region of Antwerp (Belgium). Fifty-seven (84%) of the
      parvovirus B19 immunoglobulin M (IgM)-positive sera had a positive result for
      Epstein-Barr virus (EBV) IgM by Liaison testing, 61 (90%) had a positive result
      for herpes simplex virus (HSV) IgM, 20 (29%) samples were positive for
      cytomegalovirus IgM, and 15 (22%) had a positive result for Borrelia burgdorferi
      sensu lato IgM. As assay interference was suspected, sera were further
      investigated by using additional infectious-disease serology tests and by
      performing various interference elimination procedures. We could show that the
      EBV IgM and HSV IgM results were false positives due to aspecific IgM reactions
      with the solid phase. All samples were also analyzed by a modified Liaison EBV
      IgM assay, based on the addition of polyvinylpyrrolidone and polyvinyl alcohol to
      the dilution buffer, which partially eliminated this type of assay interference.
      Although the Liaison is a very convenient, automated immunoassay platform, this
      study demonstrates the potential for improvement of mainly the EBV IgM and HSV
      IgM tests.

PMID- 19116305
TI  - Antibodies in the sera of host species with pythiosis recognize a variety of
      unique immunogens in geographically divergent Pythium insidiosum strains.
AB  - Studies by Western blot analyses have shown that antibodies in the sera of host
      species infected by Pythium insidiosum recognized several prominent proteins
      expressed by this fungus-like pathogen. Although these studies have utilized sera
      from infected patients and relevant local strains of P. insidiosum, the results
      are difficult to compare because of the lack of method standardization. In an
      effort to resolve this issue, we have utilized standardized methodologies to
      evaluate six P. insidiosum strains from Asia and the Americas and 15 serum
      samples from cattle, cats, dogs, horses, and humans with pythiosis from the same
      geographical regions. Our data show that the antibodies present in these sera
      recognize a wide variety of unique P. insidiosum immunogenic proteins. Although
      some of the prominent proteins in this study have been previously reported,
      several others have yet to be described. For instance, a approximately 28-kDa
      molecular-mass antigen was detected by the antibodies in all serum samples
      evaluated. However, this antigen was strongly expressed by only one of the
      strains evaluated. A diffuse approximately 51-kDa protein was not detected by the
      antibodies in the human sera; but it was recognized by the antibodies in the sera
      of cattle, cats, dogs, and horses. This antigen was expressed by only two of the
      strains investigated. Several other similar examples were also observed. The
      variation of the P. insidiosum protein profile identified by the antibodies in
      the sera evaluated indicates that some geographically diverged P. insidosum
      strains expressed some unique immunogens in vitro and that during natural
      infection (in vivo) P. insidiosum might express a broader number of antigens
      variably detected by individuals within the same species but especially across
      species.

PMID- 19116306
TI  - Realizing true consumer-directed health care: what the policy community needs.

PMID- 19116307
TI  - The first deletion mutation in the TSP1-6 repeat domain of ADAMTS13 in a family
      with inherited thrombotic thrombocytopenic purpura.
AB  - The inherited deficiency of ADAMTS13 is usually associated with severe forms of
      thrombotic thrombocytopenic purpura. Among the mutations identified in the
      ADAMTS13 gene, none have been described on the TSP1-6 repeat domain. We
      investigated an Iranian family with a history of chronic recurrent thrombotic
      thrombocytopenic purpura, severe ADAMTS13 deficiency and a heterogeneous pattern
      of clinical symptoms among affected members. Genetic analysis revealed a
      homozygous deletion of nucleotides 2930-2935 (GTGCCC) in exon 23 of ADAMTS13,
      leading to the replacement of Cys977 by a Trp and the deletion of Ala978 and
      Arg979 in the TSP1-6 repeat domain. To explore the mechanism of ADAMTS13
      deficiency, in vitro expression studies were performed. Western blotting, pulse
      chase labeling and immunofluorescence studies demonstrated a secretion pathway
      defect of the mutant protein, with no intracellular accumulation. This finding is
      consistent with the severe ADAMTS13 deficiency but does not explain the
      heterogeneous clinical picture of the 3 siblings carrying the same mutation.

PMID- 19116308
TI  - The subcellular distribution of an RNA quality control protein, the Ro
      autoantigen, is regulated by noncoding Y RNA binding.
AB  - The Ro autoantigen is a ring-shaped RNA-binding protein that binds misfolded RNAs
      in nuclei and is proposed to function in quality control. In the cytoplasm, Ro
      binds noncoding RNAs, called Y RNAs, that inhibit access of Ro to other RNAs. Ro
      also assists survival of mammalian cells and at least one bacterium after UV
      irradiation. In mammals, Ro undergoes dramatic localization changes after UV
      irradiation, changing from mostly cytoplasmic to predominantly nuclear. Here, we
      report that a second role of Y RNAs is to regulate the subcellular distribution
      of Ro. A mutant Ro protein that does not bind Y RNAs accumulates in nuclei. Ro
      also localizes to nuclei when Y RNAs are depleted. By assaying chimeric proteins
      in which portions of mouse Ro were replaced with bacterial Ro sequences, we show
      that nuclear accumulation of Ro after irradiation requires sequences that overlap
      the Y RNA binding site. Ro also accumulates in nuclei after oxidative stress, and
      similar sequences are required. Together, these data reveal that Ro contains a
      signal for nuclear accumulation that is masked by a bound Y RNA and suggest that
      Y RNA binding may be modulated during cell stress.

PMID- 19116309
TI  - Kinesin-14 family proteins HSET/XCTK2 control spindle length by cross-linking and
      sliding microtubules.
AB  - Kinesin-14 family proteins are minus-end directed motors that cross-link
      microtubules and play key roles during spindle assembly. We showed previously
      that the Xenopus Kinesin-14 XCTK2 is regulated by Ran via the association of a
      bipartite NLS in the tail of XCTK2 with importin alpha/beta, which regulates its
      ability to cross-link microtubules during spindle formation. Here we show that
      mutation of the nuclear localization signal (NLS) of human Kinesin-14 HSET caused
      an accumulation of HSET in the cytoplasm, which resulted in strong microtubule
      bundling. HSET overexpression in HeLa cells resulted in longer spindles, similar
      to what was seen with NLS mutants of XCTK2 in extracts, suggesting that Kinesin
      14 proteins play similar roles in extracts and in somatic cells. Conversely, HSET
      knockdown by RNAi resulted in shorter spindles but did not affect pole formation.
      The change in spindle length was not dependent on K-fibers, as elimination of the
      K-fiber by Nuf2 RNAi resulted in an increase in spindle length that was partially
      rescued by co-RNAi of HSET. However, these changes in spindle length did require
      microtubule sliding, as overexpression of an HSET mutant that had its sliding
      activity uncoupled from its ATPase activity resulted in cells with spindle
      lengths shorter than cells overexpressing wild-type HSET. Our results are
      consistent with a model in which Ran regulates the association of Kinesin-14s
      with importin alpha/beta to prevent aberrant cross-linking and bundling of
      microtubules by sequestering Kinesin-14s in the nucleus during interphase.
      Kinesin-14s act during mitosis to cross-link and slide between parallel
      microtubules to regulate spindle length.

PMID- 19116311
TI  - The conserved RIC-3 coiled-coil domain mediates receptor-specific interactions
      with nicotinic acetylcholine receptors.
AB  - RIC-3 belongs to a conserved family of proteins influencing nicotinic
      acetylcholine receptor (nAChR) maturation. RIC-3 proteins are integral membrane
      proteins residing in the endoplasmic reticulum (ER), and containing a C-terminal
      coiled-coil domain (CC-I). Conservation of CC-I in all RIC-3 family members
      indicates its importance; however, previous studies could not show its function.
      To examine the role of CC-I, we studied effects of its deletion on Caenorhabditis
      elegans nAChRs in vivo. Presence of CC-I promoted maturation of particular nAChRs
      expressed in body-wall muscle, whereas it was not required for other nAChR
      subtypes expressed in neurons or pharyngeal muscles. This effect is receptor
      specific, because it could be reproduced after heterologous expression.
      Consistently, coimmunoprecipitation analysis showed that CC-I enhances the
      interaction of RIC-3 with a nAChR that requires CC-I in vivo; thus CC-I appears
      to enhance affinity of RIC-3 to specific nAChRs. However, we found that this
      function of CC-I is redundant with functions of sequences downstream to CC-I,
      potentially a second coiled-coil. Alternative splicing in both vertebrates and
      invertebrates generates RIC-3 transcripts that lack the entire C-terminus, or
      only CC-I. Thus, our results suggest that RIC-3 alternative splicing enables
      subtype specific regulation of nAChR maturation.

PMID- 19116310
TI  - PTC1 is required for vacuole inheritance and promotes the association of the
      myosin-V vacuole-specific receptor complex.
AB  - Organelle inheritance occurs during cell division. In Saccharomyces cerevisiae,
      inheritance of the vacuole, and the distribution of mitochondria and cortical
      endoplasmic reticulum are regulated by Ptc1p, a type 2C protein phosphatase. Here
      we show that PTC1/VAC10 controls the distribution of additional cargoes moved by
      a myosin-V motor. These include peroxisomes, secretory vesicles, cargoes of
      Myo2p, and ASH1 mRNA, a cargo of Myo4p. We find that Ptc1p is required for the
      proper distribution of both Myo2p and Myo4p. Surprisingly, PTC1 is also required
      to maintain the steady-state levels of organelle-specific receptors, including
      Vac17p, Inp2p, and Mmr1p, which attach Myo2p to the vacuole, peroxisomes, and
      mitochondria, respectively. Furthermore, Vac17p fused to the cargo-binding domain
      of Myo2p suppressed the vacuole inheritance defect in ptc1Delta cells. These
      findings suggest that PTC1 promotes the association of myosin-V with its
      organelle-specific adaptor proteins. Moreover, these observations suggest that
      despite the existence of organelle-specific receptors, there is a higher order
      regulation that coordinates the movement of diverse cellular components.

PMID- 19116312
TI  - Genome-wide analysis of AP-3-dependent protein transport in yeast.
AB  - The evolutionarily conserved adaptor protein-3 (AP-3) complex mediates cargo
      selective transport to lysosomes and lysosome-related organelles. To identify
      proteins that function in AP-3-mediated transport, we performed a genome-wide
      screen in Saccharomyces cerevisiae for defects in the vacuolar maturation of
      alkaline phosphatase (ALP), a cargo of the AP-3 pathway. Forty-nine gene deletion
      strains were identified that accumulated precursor ALP, many with established
      defects in vacuolar protein transport. Maturation of a vacuolar membrane protein
      delivered via a separate, clathrin-dependent pathway, was affected in all strains
      except those with deletions of YCK3, encoding a vacuolar type I casein kinase;
      SVP26, encoding an endoplasmic reticulum (ER) export receptor for ALP; and AP-3
      subunit genes. Subcellular fractionation and fluorescence microscopy revealed ALP
      transport defects in yck3Delta cells. Characterization of svp26Delta cells
      revealed a role for Svp26p in ER export of only a subset of type II membrane
      proteins. Finally, ALP maturation kinetics in vac8Delta and vac17Delta cells
      suggests that vacuole inheritance is important for rapid generation of
      proteolytically active vacuolar compartments in daughter cells. We propose that
      the cargo-selective nature of the AP-3 pathway in yeast is achieved by AP-3 and
      Yck3p functioning in concert with machinery shared by other vacuolar transport
      pathways.

PMID- 19116313
TI  - Galectin-1 induces reversible phosphatidylserine exposure at the plasma membrane.
AB  - Cells normally undergo physiological turnover through the induction of apoptosis
      and phagocytic removal, partly through exposure of cell surface
      phosphatidylserine (PS). In contrast, neutrophils appear to possess apoptosis
      independent mechanisms of removal. Here we show that Galectin-1 (Gal-1) induces
      PS exposure independent of alterations in mitochondrial potential, caspase
      activation, or cell death. Furthermore, Gal-1-induced PS exposure reverts after
      Gal-1 removal without altering cell viability. Gal-1-induced PS exposure is
      uniquely microdomain restricted, yet cells exposing PS do not display evident
      alterations in membrane morphology nor do they exhibit bleb formation, typically
      seen in apoptotic cells. Long-term exposure to Gal-1 prolongs PS exposure with no
      alteration in cell cycle progression or cell growth. These results demonstrate
      that Gal-1-induced PS exposure and subsequent phagocytic removal of living cells
      represents a new paradigm in cellular turnover.

PMID- 19116314
TI  - Localization to mature melanosomes by virtue of cytoplasmic dileucine motifs is
      required for human OCA2 function.
AB  - Oculocutaneous albinism type 2 is caused by defects in the gene OCA2, encoding a
      pigment cell-specific, 12-transmembrane domain protein with homology to ion
      permeases. The function of the OCA2 protein remains unknown, and its subcellular
      localization is under debate. Here, we show that endogenous OCA2 in melanocytic
      cells rapidly exits the endoplasmic reticulum (ER) and thus does not behave as a
      resident ER protein. Consistently, exogenously expressed OCA2 localizes within
      melanocytes to melanosomes, and, like other melanosomal proteins, localizes to
      lysosomes when expressed in nonpigment cells. Mutagenized OCA2 transgenes
      stimulate melanin synthesis in OCA2-deficient cells when localized to melanosomes
      but not when specifically retained in the ER, contradicting a proposed primary
      function for OCA2 in the ER. Steady-state melanosomal localization requires a
      conserved consensus acidic dileucine-based sorting motif within the cytoplasmic N
      terminal region of OCA2. A second dileucine signal within this region confers
      steady-state lysosomal localization in melanocytes, suggesting that OCA2 might
      traverse multiple sequential or parallel trafficking routes. The two dileucine
      signals physically interact in a differential manner with cytoplasmic adaptors
      known to function in trafficking other proteins to melanosomes. We conclude that
      OCA2 is targeted to and functions within melanosomes but that residence within
      melanosomes may be regulated by secondary or alternative targeting to lysosomes.

PMID- 19116316
TI  - The E3 ubiquitin ligase atrophin interacting protein 4 binds directly to the
      chemokine receptor CXCR4 via a novel WW domain-mediated interaction.
AB  - The E3 ubiquitin ligase atrophin interacting protein 4 (AIP4) mediates
      ubiquitination and down-regulation of the chemokine receptor CXCR4. AIP4 belongs
      to the Nedd4-like homologous to E6-AP carboxy terminus domain family of E3
      ubiquitin ligases, which typically bind proline-rich motifs within target
      proteins via the WW domains. The intracellular domains of CXCR4 lack canonical WW
      domain binding motifs; thus, whether AIP4 is targeted to CXCR4 directly or
      indirectly via an adaptor protein remains unknown. Here, we show that AIP4 can
      interact directly with CXCR4 via a novel noncanonical WW domain-mediated
      interaction involving serine residues 324 and 325 within the carboxy-terminal
      tail of CXCR4. These serine residues are critical for mediating agonist-promoted
      binding of AIP4 and subsequent ubiquitination and degradation of CXCR4. These
      residues are phosphorylated upon agonist activation and phosphomimetic mutants
      show enhanced binding to AIP4, suggesting a mechanism whereby phosphorylation
      mediates the interaction between CXCR4 and AIP4. Our data reveal a novel
      noncanonical WW domain-mediated interaction involving phosphorylated serine
      residues in the absence of any proline residues and suggest a novel mechanism
      whereby an E3 ubiquitin ligase is targeted directly to an activated G protein
      coupled receptor.

PMID- 19116315
TI  - Cohesin associates with spindle poles in a mitosis-specific manner and functions
      in spindle assembly in vertebrate cells.
AB  - Cohesin is an essential protein complex required for sister chromatid cohesion.
      Cohesin associates with chromosomes and establishes sister chromatid cohesion
      during interphase. During metaphase, a small amount of cohesin remains at the
      chromosome-pairing domain, mainly at the centromeres, whereas the majority of
      cohesin resides in the cytoplasm, where its functions remain unclear. We describe
      the mitosis-specific recruitment of cohesin to the spindle poles through its
      association with centrosomes and interaction with nuclear mitotic apparatus
      protein (NuMA). Overexpression of NuMA enhances cohesin accumulation at spindle
      poles. Although transient cohesin depletion does not lead to visible impairment
      of normal spindle formation, recovery from nocodazole-induced spindle disruption
      was significantly impaired. Importantly, selective blocking of cohesin
      localization to centromeres, which disrupts centromeric sister chromatid
      cohesion, had no effect on this spindle reassembly process, clearly separating
      the roles of cohesin at kinetochores and spindle poles. In vitro, chromosome
      independent spindle assembly using mitotic extracts was compromised by cohesin
      depletion, and it was rescued by addition of cohesin that was isolated from
      mitotic, but not S phase, cells. The combined results identify a novel spindle
      associated role for human cohesin during mitosis, in addition to its function at
      the centromere/kinetochore regions.

PMID- 19116318
TI  - Screening for iron deficiency during early infancy: is it feasible and is it
      necessary?

PMID- 19116317
TI  - 13C natural abundance in serum retinol acts as a biomarker for increases in
      dietary provitamin A.
AB  - The natural isotopic composition of 13C and 12C in tissues is largely determined
      by the diet. Sources of provitamin A carotenoids (e.g., vegetables) typically
      have a lower 13C to 12C ratio (13C:12C) than preformed vitamin A sources (i.e.,
      dairy and meat) from corn-fed animals, which are prevalent in the US. The 13C:12C
      of serum retinol (13C:12C-retinol) was evaluated as a biomarker for vegetable
      intake in a 3-mo dietary intervention designed to promote weight-loss by
      increased vegetable consumption or reduced calorie and fat intake. Subjects were
      21-50 y of age with a BMI between 30-40 kg/m2 and were enrolled from one
      geographic area in the US. The high vegetable group (n=20) was encouraged to
      increase daily vegetable and fruit consumption to 0.95 liter vegetables and 0.24
      0.35 liter fruits. The caloric reduction group (n=17) was encouraged to lower
      caloric intake by 500 kcal and consume<or=25% kcal from fat daily. Provided meals
      supplied 75-100% vegetable and fruit goals and 50-67% kcal and fat g per day.
      Carotenoid supplementation was discontinued by subjects during the study. Serum
      retinol and provitamin A carotenoid concentrations; intake of preformed vitamin
      A, provitamin A, and fat; and body weight, fat mass, and lean mass were analyzed
      for correlations to 13C:12C-retinol. 13C:12C-Retinol decreased in the vegetable
      group after intervention (P=0.050) and the correlation with provitamin A intake
      was approaching significance (P=0.079). 13C:12C-Retinol did not change in the
      caloric reduction group (P=0.43). 13C:12C-Retinol changes with the vitamin A
      source in the diet and can be used as a biomarker for increases in dietary
      provitamin A vegetable intake.

PMID- 19116319
TI  - Is maternal diet supplementation beneficial? Optimal development of infant
      depends on mother's diet.
AB  - There are periods during perinatal development in which specific nutrients are
      required for optimal development, and there is growing evidence that optimal
      dietary intake of these nutrients, which include iodine, docosahexaenoic acid,
      choline, and folate, is important. Lessons in how these nutrient effects were
      identified can help us to broaden our approaches for finding other critical
      nutrients: we are looking for nutrients for which there is a wide range of
      dietary intake, that have no or marginal pathways for biosynthesis, and that are
      needed by dividing progenitor cells. For some of the nutrients discussed, such as
      iodine and folate, the effects in humans are abundantly clear; for others, animal
      data are the most convincing. More human studies need to be conducted. We need a
      better understanding of diet and diet supplement intake during pregnancy and
      lactation and of whether diets are particularly low in some nutrients. Also, we
      need to understand how common genetic variations influence nutrient requirements
      during these periods. If we are going to supplement maternal and infant diets,
      first we must understand much more about the risks of having too much of a
      critical nutrient. Whatever the limitations of our current state of knowledge, it
      is apparent that pregnancy and lactation are periods during which good nutrition
      is exceptionally important. The infant is not protected from the inadequate diet
      of the mother.

PMID- 19116321
TI  - Genetic polymorphisms of the vitamin D binding protein and plasma concentrations
      of 25-hydroxyvitamin D in premenopausal women.
AB  - BACKGROUND: Vitamin D status, determined on the basis of 25-hydroxyvitamin D
      [25(OH)D] concentrations, is associated with the risk of several diseases.
      Vitamin D binding protein (DBP) is the major carrier of vitamin D and its
      metabolites, but the role of DBP single nucleotide polymorphisms (SNPs) on
      25(OH)D concentrations is unclear. OBJECTIVE: The objective was to evaluate the
      association of 2 DBP gene SNPs with 25(OH)D concentrations and explore whether
      such association varies according to the amount of vitamin D that needs to be
      transported. DESIGN: This cross-sectional study included 741 premenopausal white
      women, mostly of French descent. Plasma 25(OH)D concentrations were measured by
      radioimmunoassay. DBP-1 (rs7041) and DBP-2 (rs4588) were genotyped with a
      Sequenom MassArray platform. Associations and interactions were modeled by using
      multivariate linear regression. RESULTS: DBP-1 and DBP-2 SNPs were in strong
      linkage disequilibrium and were both associated with 25(OH)D concentrations. An
      additional copy of the rare allele of DBP-1 or DBP-2 was associated with lower
      25(OH)D concentrations (beta = -3.29, P for trend = 0.0003; beta = -4.22, P for
      trend < 0.0001, respectively). These DBP polymorphisms explained as much of the
      variation in circulating 25(OH)D as did total vitamin D intake (r2 = 1.3% for DBP
      1, r2 = 2.0% for DBP-2, and r2 < or = 1.2% for vitamin D intake). CONCLUSION:
      Circulating 25(OH)D concentrations in premenopausal women are strongly related to
      DBP polymorphisms. Whether DBP rare allele carriers have a different risk of
      vitamin D-related diseases and whether such carriers can benefit more or less
      from dietary interventions, vitamin D supplementation, or sun exposure need to be
      clarified.

PMID- 19116320
TI  - Importance of methyl donors during reproduction.
AB  - Evidence is growing that optimal dietary intake of folate and choline (both
      involved in one-carbon transfer or methylation) is important for successful
      completion of fetal development. Significant portions of the population are
      eating diets low in one or both of these nutrients. Folates are important for
      normal neural tube closure in early gestation, and the efficacy of diet
      fortification with folic acid in reducing the incidence of neural tube defects is
      a major success story for public health nutrition. Similarly, maternal dietary
      choline is important for normal neural tube closure in the fetus and, later in
      gestation, for neurogenesis in the fetal hippocampus, with effects on memory that
      persist in adult offspring; higher choline intake is associated with enhanced
      memory performance. Although both folates and choline have many potentially
      independent mechanisms whereby they could influence fetal development, these 2
      nutrients also have a common mechanism for action: altered methylation and
      related epigenetic effects on gene expression.

PMID- 19116322
TI  - Ethyl-eicosapentaenoic acid for the treatment of psychological distress and
      depressive symptoms in middle-aged women: a double-blind, placebo-controlled,
      randomized clinical trial.
AB  - BACKGROUND: Psychological distress (PD) and depressive symptoms are commonly
      observed during menopausal transition. Studies suggest that omega-3 (n-3) fatty
      acids may help alleviate depression. OBJECTIVE: The objective was to compare
      enriched ethyl-eicosapentaenoic acid (E-EPA) supplementation with placebo for the
      treatment of PD and depressive symptoms in middle-aged women. DESIGN: Women with
      moderate-to-severe PD (n = 120) were randomly assigned to receive 1.05 g E-EPA/d
      plus 0.15 g ethyl-docosahexaenoic acid/d (n = 59) or placebo (n = 61) for 8 wk.
      The main outcomes were 8-wk changes in PD scores [Psychological General Well
      Being Schedule (PGWB)] and depressive scales [20-item Hopkins Symptom Checklist
      Depression Scale (HSCL-D-20) and the 21-item Hamilton Depression Rating Scale
      (HAM-D-21)]. RESULTS: At baseline, women with PD were mildly to moderately
      depressed, and 24% met the major depressive episode (MDE) criteria of the
      Diagnostic and Statistical Manual of Mental Disorders, 4th edition. After 8 wk,
      outcomes improved in both groups, but no significant differences were noted
      between them. Stratification analyses for MDE diagnosis at baseline indicated
      that differences in adjusted 8-wk changes between the E-EPA group without MDE (n
      = 46) and the placebo group (n = 45) were 8.0 (95% CI: 0.6, 15.3; P = 0.034) for
      the PGWB, -0.2 (95% CI: -0.01, -0.4; P = 0.040) for the HSCL-D-20, and -2.7 (95%
      CI: -0.3, -5.1; P = 0.030) for the HAM-D-21. Differences in adjusted 8-wk changes
      between the E-EPA group with MDE (n = 13) and the placebo group (n = 16) were not
      significant. CONCLUSIONS: To our knowledge, this is the first trial of n-3
      supplementation in the treatment of PD and depressive symptoms in middle-aged
      women. In women with PD without MDE at baseline, the 8-wk changes in PD and
      depressive scales improved significantly more with E-EPA than with placebo. This
      trial was registered at http://www.controlled-trials.com as ISRCTN69617477.

PMID- 19116323
TI  - How common is vitamin B-12 deficiency?
AB  - In considering the vitamin B-12 fortification of flour, it is important to know
      who is at risk of vitamin B-12 deficiency and whether those individuals would
      benefit from flour fortification. This article reviews current knowledge of the
      prevalence and causes of vitamin B-12 deficiency and considers whether
      fortification would improve the status of deficient subgroups of the population.
      In large surveys in the United States and the United Kingdom, approximately 6% of
      those aged > or =60 y are vitamin B-12 deficient (plasma vitamin B-12 < 148
      pmol/L), with the prevalence of deficiency increasing with age. Closer to 20%
      have marginal status (plasma vitamin B-12: 148-221 pmol/L) in later life. In
      developing countries, deficiency is much more common, starting in early life and
      persisting across the life span. Inadequate intake, due to low consumption of
      animal-source foods, is the main cause of low serum vitamin B-12 in younger
      adults and likely the main cause in poor populations worldwide; in most studies,
      serum vitamin B-12 concentration is correlated with intake of this vitamin. In
      older persons, food-bound cobalamin malabsorption becomes the predominant cause
      of deficiency, at least in part due to gastric atrophy, but it is likely that
      most elderly can absorb the vitamin from fortified food. Fortification of flour
      with vitamin B-12 is likely to improve the status of most persons with low stores
      of this vitamin. However, intervention studies are still needed to assess
      efficacy and functional benefits of increasing intake of the amounts likely to be
      consumed in flour, including in elderly persons with varying degrees of gastric
      atrophy.

PMID- 19116325
TI  - Breastfeeding and reduced risk of childhood obesity: will randomized trials on
      breastfeeding promotion give the definite answer?

PMID- 19116324
TI  - Docosahexaenoic acid supplementation in pregnancy and lactation.
AB  - The goal of the Experimental Biology symposium on maternal supplementation was to
      review all available lines of evidence, delineate unanswered questions, and
      develop, if it seemed reasonable, a research agenda to determine whether maternal
      supplementation with specific nutrients might be beneficial. In the case of
      maternal docosahexaenoic acid (DHA) status, the topic addressed in this article,
      few clinical studies show benefits of maternal DHA supplementation during
      pregnancy or lactation for the infant or child. However, quite a large number of
      observational studies link higher intrauterine DHA exposure to a number of
      positive developmental outcomes. This article reviews the factors known to
      contribute to DHA status of women and their offspring during the reproductive
      cycle, relates maternal DHA status to that of the developing fetus and newborn,
      and reviews the evidence for functional differences in behavior related to DHA
      status, including the available evidence related to DHA supplementation of women
      pregnant and lactating and their offspring. Other outcomes for infants and
      children and for women themselves appear plausible and are also addressed as part
      of a research agenda for future work.

PMID- 19116327
TI  - Methyl donors, iodine, and DHA--is maternal supplementation beneficial?
      Introduction.

PMID- 19116326
TI  - Vitamin E intake, alpha-tocopherol status, and pancreatic cancer in a cohort of
      male smokers.
AB  - BACKGROUND: Evidence indicates that vitamin E has anticarcinogenic properties for
      gastrointestinal cancers; however, few studies have examined this with respect to
      exocrine pancreatic cancer. OBJECTIVE: The objective was to examine whether
      vitamin E intake and serum alpha-tocopherol concentrations were prospectively
      associated with exocrine pancreatic cancer. DESIGN: We conducted a cohort
      analysis of prediagnostic vitamin E intake (4 tocopherols, 4 tocotrienols), serum
      alpha-tocopherol concentrations, and pancreatic cancer in the Alpha-Tocopherol,
      Beta-Carotene Cancer Prevention (ATBC) Study of male Finnish smokers aged 50-69 y
      at baseline. During follow-up from 1985 to 2004 (maximum: 19.4 y; median: 16 y),
      318 incident cases were diagnosed among cohort participants with complete serum
      samples (n = 29,092); 306 cases had complete dietary data (n = 27,111). Cox
      proportional hazards models adjusted for age, smoking history, history of
      diabetes mellitus, and/or serum cholesterol were used to calculate hazard ratios
      (HRs) and 95% CIs. RESULTS: Higher alpha-tocopherol concentrations were
      associated with lower pancreatic cancer risk (highest compared with lowest
      quintile, HR: 0.52; 95% CI: 0.34, 0.80; P for trend = 0.03; continuous HR: 0.91;
      95% CI: 0.84, 0.99). Polyunsaturated fat, a putative prooxidant nutrient,
      modified the association such that the inverse alpha-tocopherol association was
      most pronounced in subjects with a high polyunsaturated fat intake (ie, >9.9 g/d;
      highest compared with lowest quintile, HR: 0.38; 95% CI: 0.20, 0.70; P for trend
      = 0.03; continuous HR: 0.86; 95% CI: 0.75, 0.97; P for interaction = 0.05 and
      0.02, respectively). No associations were observed for dietary tocopherols and
      tocotrienols. CONCLUSION: Our results support the hypothesis that higher alpha
      tocopherol concentrations may play a protective role in pancreatic carcinogenesis
      in male smokers.

PMID- 19116328
TI  - Association of 1-y changes in diet pattern with cardiovascular disease risk
      factors and adipokines: results from the 1-y randomized Oslo Diet and Exercise
      Study.
AB  - BACKGROUND: We hypothesized that favorable changes in dietary patterns would lead
      to a reduction in body size and an improvement in metabolic status. OBJECTIVE:
      The objective was to study changes in diet patterns relative to changes in body
      size, blood pressure, and circulating concentrations of lipids, glucose, insulin,
      adiponectin, and other cytokines in the context of a 1-y randomized intervention
      study. DESIGN: For 1 y, 187 men aged 45 +/- 2 y, approximately 50% of whom met
      the criteria of the metabolic syndrome, were randomly assigned to a diet protocol
      (n = 45), an exercise protocol (n = 48), a protocol of diet plus exercise (n =
      58), or a control protocol (n = 36). A previously defined a priori diet score was
      created by summing tertile rankings of 35 food group variables; a higher score
      generally reflected recommended dietary changes in the trial (mean +/- SD at
      baseline: 31 +/- 6.5; range: 15-47). RESULTS: Over the study year, the diet score
      increased by approximately 2 +/- 5.5 in both diet groups, with a decrease of an
      equivalent amount in the exercise and control groups. The weight change was -3.5
      +/- 0.6 kg/10-point change in diet score (P < 0.0001), similarly within each
      intervention group, independently of the change in energy intake or baseline age
      and smoking status. Weight change was attenuated but remained significant after
      adjustment for intervention group and percentage body fat. Subjects with an
      increased diet score had more favorable changes in other body size variables,
      systolic blood pressure, and blood lipid, glucose, insulin, and adiponectin
      concentrations. Change in diet score was unrelated to resistin and several
      cytokines. CONCLUSION: The change toward a more favorable diet pattern was
      associated with improved body size and metabolic profile.

PMID- 19116329
TI  - Comparisons of percentage body fat, body mass index, waist circumference, and
      waist-stature ratio in adults.
AB  - BACKGROUND: Body mass index (BMI), waist circumference (WC), and the waist
      stature ratio (WSR) are considered to be possible proxies for adiposity.
      OBJECTIVE: The objective was to investigate the relations between BMI, WC, WSR,
      and percentage body fat (measured by dual-energy X-ray absorptiometry) in adults
      in a large nationally representative US population sample from the National
      Health and Nutrition Examination Survey (NHANES). DESIGN: BMI, WC, and WSR were
      compared with percentage body fat in a sample of 12,901 adults. RESULTS: WC, WSR,
      and BMI were significantly more correlated with each other than with percentage
      body fat (P < 0.0001 for all sex-age groups). Percentage body fat tended to be
      significantly more correlated with WC than with BMI in men but significantly more
      correlated with BMI than with WC in women (P < 0.0001 except in the oldest age
      group). WSR tended to be slightly more correlated with percentage body fat than
      was WC. Percentile values of BMI, WC, and WSR are shown that correspond to
      percentiles of percentage body fat increments of 5 percentage points. More than
      90% of the sample could be categorized to within one category of percentage body
      fat by each measure. CONCLUSIONS: BMI, WC, and WSR perform similarly as
      indicators of body fatness and are more closely related to each other than with
      percentage body fat. These variables may be an inaccurate measure of percentage
      body fat for an individual, but they correspond fairly well overall with
      percentage body fat within sex-age groups and distinguish categories of
      percentage body fat.

PMID- 19116330
TI  - Reduced production of sulfated glycosaminoglycans occurs in Zambian children with
      kwashiorkor but not marasmus.
AB  - BACKGROUND: Kwashiorkor, a form of severe malnutrition with high mortality, is
      characterized by edema and systemic abnormalities. Although extremely common, its
      pathophysiology remains poorly understood, and its characteristic physical signs
      are unexplained. OBJECTIVE: Because kwashiorkor can develop in protein-losing
      enteropathy, which is caused by a loss of enterocyte heparan sulfate proteoglycan
      (HSPG), and previous observations suggest abnormal sulfated glycosaminoglycan
      (GAG) metabolism, we examined whether intestinal GAG and HSPG are abnormal in
      children with kwashiorkor. DESIGN: Duodenal biopsy samples collected from Zambian
      children with marasmus (n = 18), marasmic kwashiorkor (n = 8), and kwashiorkor (n
      = 15) were examined for expression of HSPG, GAGs, and immunologic markers and
      compared against reference samples from healthy UK control children. GAG and HSPG
      expression density and inflammatory cell populations were quantitated by
      computerized analysis. RESULTS: The kwashiorkor group was less wasted and had a
      lower HIV incidence than did the other groups. All duodenal biopsy samples showed
      inflammation compared with the histologically uninflamed control samples. Biopsy
      samples from marasmic children had greater inflammation and greater CD3+ and HLA
      DR (human leukocyte antigen DR)-positive cell densities than did samples from
      children with kwashiorkor. Expression of both HSPG and GAGs was similar between
      marasmic and well-nourished UK children but was markedly lower in children with
      kwashiorkor in both the epithelium and lamina propria. Although underglycosylated
      and undersulfated, epithelial syndecan-1 protein was normally expressed in
      kwashiorkor, which confirmed that abnormalities arise after core protein
      synthesis. CONCLUSIONS: Intestinal HSPG loss occurs in kwashiorkor, which may
      precipitate protein-losing enteropathy to cause edema. If occurring systemically,
      impaired HSPG expression could cause several previously unexplained features of
      kwashiorkor. We speculate that a genetic predisposition to reduced HSPG
      biosynthesis may offer a contrasting selective advantage, by both diminishing
      protein catabolism during transient undernutrition and protecting against
      specific infectious diseases.

PMID- 19116331
TI  - Folate and one-carbon metabolism nutrients from supplements and diet in relation
      to breast cancer risk.
AB  - BACKGROUND: Few epidemiologic studies have examined very high intakes of folate
      and whether consumption of nutrients involved in one-carbon metabolism is
      associated with breast cancer risk. OBJECTIVE: We prospectively examined whether
      the consumption of folate and nutrients involved in one-carbon metabolism
      (methionine, riboflavin, and vitamins B-6 and B-12) from self-reported intakes of
      diet (in year before baseline) and supplements (averaged over 10 y before
      baseline) were associated with the incidence of breast cancer and breast cancer
      tumor characteristics. DESIGN: Participants were 35,023 postmenopausal women aged
      50-76 y in the VITamins And Lifestyle (VITAL) cohort study; breast cancer was
      diagnosed in 743 of these women between baseline (2000-2002) and 2006. Cox
      proportional hazards models were used to estimate multivariable-adjusted relative
      risks (RRs) and 95% CIs. RESULTS: Women consuming > or =1272 dietary folate
      equivalents (DFE)/d of total folate (10-y average) had a 22% decrease in breast
      cancer risk compared with women consuming < or =345 DFE/d (RR: 0.78; 95% CI:
      0.61, 0.99; P for trend = 0.05). A greater benefit was observed for estrogen
      receptor (ER) negative than for ER+ breast cancers (RR: 0.38; 95% CI: 0.18, 0.80;
      P for trend = 0.02; P = 0.02 for the difference between ER- and ER+). Neither
      current intakes of folate nor current or long-term intakes of other one-carbon
      nutrients were significantly associated with breast cancer risk. Multivitamin use
      attenuated the increased risk of breast cancer associated with alcohol drinking
      (P for interaction = 0.02). CONCLUSIONS: Our study of predominantly supplement
      users suggests that high intakes of folate averaged over 10 y do not increase
      breast cancer risk, but may be protective, particularly against ER- breast
      cancers.

PMID- 19116332
TI  - Vitamin B-12 and cognition in the elderly.
AB  - Vitamin B-12 deficiency is often associated with cognitive deficits. Here we
      review evidence that cognition in the elderly may also be adversely affected at
      concentrations of vitamin B-12 above the traditional cutoffs for deficiency. By
      using markers such as holotranscobalamin and methylmalonic acid, it has been
      found that cognition is associated with vitamin B-12 status across the normal
      range. Possible mediators of this relation include brain atrophy and white matter
      damage, both of which are associated with low vitamin B-12 status. Intervention
      trials have not been adequately designed to test whether these associations are
      causal. Pending the outcome of better trials, it is suggested that the elderly in
      particular should be encouraged to maintain a good, rather than just an adequate,
      vitamin B-12 status by dietary means.

PMID- 19116333
TI  - Folate concentrations in pediatric patients with newly diagnosed inflammatory
      bowel disease.
AB  - BACKGROUND: Folate is postulated to protect against cell injury and long-term
      risk of cancer. Folate deficiency has been shown to be associated with
      inflammatory bowel disease (IBD). However, folate concentrations are poorly
      delineated in children with IBD. OBJECTIVE: The objective was to compare folate
      concentrations between children with newly diagnosed IBD and healthy controls.
      DESIGN: Red blood cell folate (RBCF) and whole-blood folate (WBF) concentrations
      were measured in 78 children (mean age: 12.8 +/- 2.7 y): 22 patients with newly
      diagnosed untreated Crohn disease, 11 patients with ulcerative colitis, 4
      patients with indeterminate colitis, and 41 controls. Vitamin supplementation and
      dietary intakes determined by food-frequency questionnaire were recorded for 20
      IBD patients and 28 controls. RESULTS: RBCF concentrations were 19.4% lower in
      controls (587.0 +/- 148.6 ng/mL) than in patients (728.7 +/- 185.8 ng/mL; P =
      0.0004), and WBF concentrations were 11.1% lower in controls (218.2 +/- 49.7
      ng/mL) than in patients (245.3 +/- 59.1 ng/mL; P = 0.031). Total folate intake
      was 18.8% higher in controls (444.7 +/- 266.7 microg/d) than in IBD patients
      (361.1 +/- 230.6 microg/d), but this difference was not statistically significant
      (P = 0.264). Folate intakes were below the Recommended Dietary Allowance (200-400
      microg/d), adjusted for age and sex, in 35.4% of study subjects. CONCLUSIONS: In
      contrast with previous evidence of folate deficiency in adult IBD patients, our
      data indicate higher folate concentrations in children with newly diagnosed
      untreated IBD than in controls. This finding was unexpected, especially in light
      of the higher dietary folate intakes and hematocrit values in children without
      IBD. The influence of IBD therapy on folate metabolism and the long-term clinical
      implications of high RBCF and WBF concentrations at the time of IBD diagnosis
      should be explored further.

PMID- 19116334
TI  - Vitamin B-12 and neural tube defects: the Canadian experience.
AB  - Although early epidemiologic studies showed a protective effect of adequate
      maternal folic acid (FA) status against neural tube defects (NTDs), the role of
      adequate vitamin B-12 nutrition in the putative reduction of NTD frequency has
      remained uncertain. Evaluating vitamin B-12 status was complicated by the need to
      control for altered FA status after fortification in Canada. More recent studies
      have made use of better biomarkers of vitamin B-12 status, including
      methylmalonic acid and holotranscobalamin (holoTC). HoloTC provides a useful
      measure of vitamin B-12 status because it represents the bioavailable fraction of
      circulating vitamin B-12. By assessing bioavailable vitamin B-12 status in a
      large Canadian cohort accrued before and after FA fortification, we found a 3
      fold increase in the risk of NTDs in mothers who had vitamin B-12 status in the
      lower quartile, regardless of FA fortification. Our work suggests that vitamin B
      12 fortification, analogous to the FA fortification program, may reduce NTDs more
      than FA fortification alone. A multicenter randomized controlled trial comparing
      periconceptional vitamin B-12 in combination with FA against FA alone is
      warranted.

PMID- 19116335
TI  - Letter to the editor: "Zinc and cardioprotection: the missing link".

PMID- 19116337
TI  - Minireview: 3-Iodothyronamine (T1AM): a new player on the thyroid endocrine team?
AB  - 3-Iodothyronamine (T(1)AM) is an endogenous compound with chemical features that
      are similar to thyroid hormone. T(1)AM has a carbon skeleton identical to that of
      T(4) and contains a single carbon-iodine bond. Theoretically, T(1)AM could be
      produced from T(4) by enzymatic decarboxylation and deiodination. Recent studies
      show that T(1)AM and higher iodinated thyronamines are subject to similar
      metabolic processing as iodothyronines such as T(4), suggesting a biological
      linkage between iodothyronines and iodothyronamines. In addition, single doses of
      T(1)AM administered to rodents induce a hypometabolic state that in certain ways
      resembles hibernation and is opposite to the effects of excess T(4). This review
      will discuss the latest developments on this recently discovered thyroid hormone
      derivative.

PMID- 19116338
TI  - Epidermal growth factor receptor pathway substrate 8 is overexpressed in human
      pituitary tumors: role in proliferation and survival.
AB  - Based on prior work showing that human pituitary tumors overexpress epidermal and
      fibroblast growth factor receptors, we hypothesized that downstream components of
      growth factor signaling pathways may also be dysregulated. Epidermal growth
      factor pathway substrate number 8 (Eps8) was identified as a transcript
      overexpressed (5.9-fold) in human pituitary tumors compared with normal pituitary
      by DNA microarrays. Eps8 mRNA up-regulation was confirmed by semiquantitative RT
      PCR. Immunoblot analysis showed that Eps8 protein levels and its downstream
      target phosphorylated ERK were also up-regulated in human pituitary tumors.
      Stable overexpression of Eps8 in LbetaT2 gonadotrope pituitary cells augmented
      colony formation in soft agar at d 21. Eps8 cells proliferated more robustly
      compared with controls in growth factor replete as well as growth-restricted
      conditions. In addition, the Eps8 overexpressing cells were protected from serum
      withdrawal-induced apoptosis compared with controls as assessed by caspase-3
      cleavage. Epidermal growth factor activated a robust amplification of ERK and
      modest up-regulation of Akt in Eps8-overexpressing pituitary cells compared with
      vector controls. MAPK kinase inhibition or silencing of Eps8 blunted the
      proliferation of the cells in response to growth factor stimulation. Blockade of
      the phosphatidylinositol 3-kinase pathway or silencing of Eps8 resulted in a loss
      of the Eps8 protection from growth factor withdrawal-induced apoptosis. Together
      these data support a role of Eps8 in amplifying growth factor receptor signaling
      in human pituitary tumors to promote proliferation and cell survival.

PMID- 19116339
TI  - Nocturnal activation of aurora C in rat pineal gland: its role in the
      norepinephrine-induced phosphorylation of histone H3 and gene expression.
AB  - We have shown previously that Ser10 phosphorylation of histone H3 occurs in rat
      pinealocytes after stimulation with norepinephrine (NE) and that histone
      modifications such as acetylation appear to play an important role in pineal gene
      transcription. Here we report the nocturnal phosphorylation of a Ser10 histone H3
      kinase, Aurora C, in the rat pineal gland. The time profile of this
      phosphorylation parallels the increase in the level of phospho-Ser10 histone H3.
      Studies with cultured pinealocytes indicate that Aurora C phosphorylation is
      induced by NE and this induction can be blocked by cotreatment with propranolol
      or KT5720, a protein kinase A inhibitor. Moreover, only treatment with dibutyryl
      cAMP, but not other kinase activators, mimics the effect of NE on Aurora C
      phosphorylation. These results indicate that Aurora C is phosphorylated primarily
      by a beta-adrenergic/protein kinase A-mediated mechanism. Treatment with an
      Aurora C inhibitor reduces the NE-induced histone H3 phosphorylation and
      suppresses the NE-stimulated induction of arylalkylamine N-acetyltransferase (AA
      NAT), the rhythm-controlling enzyme of melatonin synthesis, and melatonin
      production. The effects of Aurora C inhibitors on adrenergic-induced genes in rat
      pinealocytes are gene specific: inhibitory for Aa-nat and inducible cAMP
      repressor but stimulatory for c-fos. Together our results support a role for the
      NE-stimulated phosphorylation of Aurora C and the subsequent remodeling of
      chromatin in NE-stimulated Aa-nat transcription. This phenomenon suggests that
      activation of this mitotic kinase can be induced by extracellular signals to
      participate in the transcriptional induction of a subset of genes in the rat
      pineal gland.

PMID- 19116340
TI  - Characterization of relaxin receptor (RXFP1) desensitization and internalization
      in primary human decidual cells and RXFP1-transfected HEK293 cells.
AB  - We report here the desensitization and internalization of the relaxin receptor
      (RXFP1) after agonist activation in both primary human decidual cells and HEK293
      cells stably transfected with RXFP1. The importance of beta-arrestin 2 in these
      processes has also been demonstrated. Thus, in HEK-RXFP1 cells the
      desensitization of RXFP1 was significantly increased when beta-arrestin 2 was
      overexpressed. After relaxin activation, beta-arrestin 2 was translocated to the
      cell membrane and RXFP1 underwent rapid internalization. We have previously shown
      that RXFP1 forms dimers/oligomers during its biosynthesis and trafficking to the
      plasma membrane, we now show that internalization of RXFP1 occurs through this
      dimerization/oligomerization. In nonagonist stimulated cells, it is known that
      the majority of the RXFP1 is located intracellularly and was confirmed in the
      cells used here. Constitutive internalization of RXFP1 could account for this and
      indeed, slow but robust constitutive internalization, which was increased after
      agonist stimulation was demonstrated. A carboxyl-terminal deleted RXFP1 variant
      had a similar level of constitutive agonist-independent internalization as the
      wild-type RXFP1 but lost sensitivity to agonist stimulation. This demonstrated
      the importance of the carboxyl terminus in agonist-stimulated receptor
      internalization. These data suggest that the autocrine/paracrine actions of
      relaxin in the decidua are under additional controls at the level of expression
      of its receptor on the surface of its target cells.

PMID- 19116341
TI  - Dorsal hindbrain 5'-adenosine monophosphate-activated protein kinase as an
      intracellular mediator of energy balance.
AB  - The fuel-sensing enzyme AMP-activated protein kinase (AMPK) has been implicated
      in central nervous system control of energy balance. Hypothalamic AMPK activity
      is increased by food deprivation, and this elevation is inhibited by refeeding or
      by leptin treatment. The contribution of extrahypothalamic AMPK activity in
      energy balance control has not been addressed. Here, we investigate the effects
      of physiological state on the AMPK activity in hindbrain nucleus tractus
      solitarius (NTS) neurons because treatments that reduce energy availability in
      these neurons trigger behavioral, endocrine, and autonomic responses to restore
      energy balance. Food-deprived rats showed significantly increased AMPK activity
      in both NTS- and hypothalamus-enriched lysates compared with those that were ad
      libitum fed. Pharmacological inhibition of AMPK activity in medial NTS neurons,
      by intraparenchymal injection of compound C, suppressed food intake and body
      weight gain compared with vehicle. Fourth ventricle (4th i.c.v.) compound C
      delivery increased heart rate and spontaneous activity in free-moving rats.
      Suppression of AMPK activity has been implicated in leptin's anorectic action in
      the hypothalamus. Given the role of leptin signaling in food intake inhibition
      within the medial NTS, we also examined whether stimulation of hindbrain AMPK by
      4th i.c.v. administration of 5-aminoimidazole-4-carboxamide-riboside (AICAR), an
      AMP-mimicking promoter of AMPK activity, could attenuate the inhibition of food
      intake by 4th i.c.v. leptin. The intake-suppressive effects of leptin (at 2 and 4
      h) were completely reversed by AICAR. We conclude that 1) hindbrain AMPK activity
      contributes to energy balance control through regulation of food intake and
      energy expenditure, 2) leptin's intake-reducing effects in the NTS are mediated
      by AMPK, and 3) central nervous system AMPK controls whole-body homeostasis at
      anatomically distributed sites across the neuraxis.

PMID- 19116342
TI  - Identification of the potent phytoestrogen glycinol in elicited soybean (Glycine
      max).
AB  - The primary induced isoflavones in soybean, the glyceollins, have been shown to
      be potent estrogen antagonists in vitro and in vivo. The discovery of the
      glyceollins' ability to inhibit cancer cell proliferation has led to the analysis
      of estrogenic activities of other induced isoflavones. In this study, we
      investigated a novel isoflavone, glycinol, a precursor to glyceollin that is
      produced in elicited soy. Sensitive and specific in vitro bioassays were used to
      determine that glycinol exhibits potent estrogenic activity. Estrogen-based
      reporter assays were performed, and glycinol displayed a marked estrogenic effect
      on estrogen receptor (ER) signaling between 1 and 10 microM, which correlated
      with comparable colony formation of MCF-7 cells at 10 microM. Glycinol also
      induced the expression of estrogen-responsive genes (progesterone receptor and
      stromal-cell-derived factor-1). Competitive binding assays revealed a high
      affinity of glycinol for both ER alpha (IC(50) = 13.8 nM) and ER beta (IC(50) =
      9.1 nM). In addition, ligand receptor modeling (docking) studies were performed
      and glycinol was shown to bind similarly to both ER alpha and ER beta. Taken
      together, these results suggest for the first time that glycinol is estrogenic
      and may represent an important component of the health effects of soy-based
      foods.

PMID- 19116343
TI  - Pax6 haploinsufficiency causes abnormal metabolic homeostasis by down-regulating
      glucagon-like peptide 1 in mice.
AB  - Heterozygosity for the Pax6 allele is associated with impaired glucose tolerance
      in humans. With a Pax6 mutant mouse model, we found many of the metabolic
      abnormalities were consistent with the effects of down-regulating the expression
      of glucagon-like peptide 1 (GLP-1). In addition to impaired glucose tolerance,
      adult heterozygous mutant mice (Pax6(m/+)) secreted less insulin responding to
      glucose and arginine administration compared with control mice. Moreover,
      Pax6(m/+) mice showed increased food intake compared with control mice, although
      they were resistant to diet-induced fat accumulation. Indeed, levels of
      circulating GLP-1 and intestinal transcription of Gcg/Proglucagon were
      dramatically reduced in Pax6(m/+) mice. Mutated Pax6 also failed to activate the
      Gcg/Proglucagon promoter by in vitro transfection assay. Finally, administering
      the GLP-1 receptor agonist exendin-4 to Pax6(m/+) mice largely reversed their
      abnormal food intake, glycemic excursion, and insulin secretion. Our studies
      suggested that disruption of metabolic homeostasis mainly caused by Pax6
      haploinsufficiency was mainly mediated by down-regulation of GLP-1.
      Administration of exendin-4 may be a useful therapy in humans with a similar
      mutation.

PMID- 19116344
TI  - Akt2 regulation of Cdc2-like kinases (Clk/Sty), serine/arginine-rich (SR) protein
      phosphorylation, and insulin-induced alternative splicing of PKCbetaII messenger
      ribonucleic acid.
AB  - Serine/arginine-rich (SR) proteins play essential roles in the constitutive and
      regulated splicing of precursor mRNAs. Phosphorylation of the arginine/serine
      dipeptide-rich (RS) domain by SR protein kinases such as Cdc2-like kinases
      (Clk/Sty) modulates their subcellular localization and activation. However, it
      remains unclear how these kinases and their target SR proteins are regulated by
      extracellular signals. Regulation of protein kinase C betaII (PKCbetaII) pre-mRNA
      alternative splicing via exon inclusion by Akt2, a central kinase in insulin
      action, involves phosphorylation of SR proteins. Here we showed that Akt2, in
      response to insulin, resulted in phosphorylation of Clk/Sty, which then altered
      SR protein phosphorylation in concert with Akt2. Insulin-stimulated PKCbetaII pre
      mRNA splicing was blocked by Clk/Sty and phosphatidylinositol-3-kinase
      inhibitors, and diabetic Akt2-null mouse tissues had impaired phospho-Clk/Sty, SR
      protein phosphorylation, and PKCbetaII expression. Furthermore, we observed that
      Akt2 phosphorylated several SR proteins distinct from Clk/Sty in response to
      insulin. Akt2-catalyzed phosphorylation of Clk/Sty and SR proteins revealed a
      role for both kinases in splicing regulation indicating dual functions for Akt2
      in response to insulin in this pathway.

PMID- 19116345
TI  - Sphingosine kinase as an oncogene: autocrine sphingosine 1-phosphate modulates ML
      1 thyroid carcinoma cell migration by a mechanism dependent on protein kinase C
      alpha and ERK1/2.
AB  - Sphingosine 1-phosphate (S1P) induces migration of the human thyroid follicular
      carcinoma cell line ML-1 by activation of S1P(1) and S1P(3) receptors, G(i)
      proteins, and the phosphatidylinositol 3-kinase-Akt pathway. Because sphingosine
      kinase isoform 1 (SK) recently has been implicated as an oncogene in various
      cancer cell systems, we investigated the functions of SK in the migration,
      proliferation and adhesion of the ML-1 cell line. SK overexpressing ML-1 cells
      show an enhanced secretion of S1P, which can be attenuated, by inhibiting SK
      activity and a multidrug-resistant transport protein (ATP-binding cassette
      transporter). Furthermore, overexpression of SK enhances serum-induced migration
      of ML-1 cells, which can be attenuated by blocking ATP-binding cassette
      transporter and SK, suggesting that the migration is mediated by autocrine
      signaling through secretion of S1P. Inhibition of protein kinase C alpha, with
      both small interfering RNA (siRNA) and small molecular inhibitors attenuates
      migration in SK overexpressing cells. In addition, SK-overexpressing cells show
      an impaired adhesion, slower cell growth, and an up-regulation of ERK1/2
      phosphorylation, as compared with cells expressing a dominant-negative SK. Taken
      together, we present evidence suggesting that SK enhances migration of ML-1 cells
      by an autocrine mechanism and that the S1P-evoked migration is dependent on
      protein kinase C alpha, ERK1/2, and SK.

PMID- 19116346
TI  - Role of type Ialpha phosphatidylinositol-4-phosphate 5-kinase in insulin
      secretion, glucose metabolism, and membrane potential in INS-1 beta-cells.
AB  - Insulin secretion from beta-cells is regulated by a complex signaling network.
      Our earlier study has reported that Rac1 participates in glucose- and cAMP
      induced insulin secretion probably via maintaining a functional actin structure
      for recruitment of insulin granules. Type Ialpha phosphatidylinositol-4-phosphate
      5-kinase (PIP5K-Ialpha) is a downstream effector of Rac1 and a critical enzyme
      for synthesis of phosphatidylinositol-4,5-bisphosphate (PIP(2)). By using an RNA
      interference technique, PIP5K-Ialpha in INS-1 beta-cells could be specifically
      knocked down by 70-75%. PIP5K-Ialpha knockdown disrupted filamentous actin
      structure and caused changes in cell morphology. In addition, PIP(2) content in
      the plasma membrane was reduced and the glucose effect on PIP(2) was abolished
      but without affecting glucose-induced formation of inositol 1,4,5-trisphosphate.
      At basal conditions (2.8 mM glucose), PIP5K-Ialpha knockdown doubled insulin
      secretion, elevated glucose metabolic rate, depolarized resting membrane
      potential, and raised cytoplasmic free Ca(2+) levels ([Ca(2+)](i)). The total
      insulin release at high glucose was increased upon PIP5K-Ialpha knockdown.
      However, the percent increment of insulin secretion by high glucose and forskolin
      over the basal release was significantly reduced, an effect more apparent on the
      late phase of insulin secretion. Metabolism and [Ca(2+)](i) rises at high glucose
      were also attenuated in cells after PIP5K-Ialpha knockdown. In contrast, PIP5K
      Ialpha knockdown had no effect on cell growth and viability. Taken together, our
      data suggest that PIP5K-Ialpha may play an important role in both the proximal
      and distal steps of signaling cascade for insulin secretion in beta-cells.

PMID- 19116347
TI  - Utility of peptide nucleic acid fluorescence in situ hybridization for rapid
      detection of Acinetobacter spp. and Pseudomonas aeruginosa.
AB  - The utility of peptide nucleic acid fluorescence in situ hybridization (PNA FISH)
      for the detection of Acinetobacter spp. and Pseudomonas aeruginosa was evaluated
      on broth suspensions and spiked blood cultures of ATCC strains and clinical
      isolates with select gram-negative rods. After testing 60 clinical isolates, PNA
      FISH had a sensitivity and specificity of 100% and 100%, respectively, for
      Acinetobacter spp. and 100% and 95%, respectively, for P. aeruginosa. PNA FISH
      was able to detect both pathogens simultaneously and directly from spiked blood
      cultures.

PMID- 19116348
TI  - Genetic analysis of group A streptococcus isolates recovered during acute
      glomerulonephritis outbreaks in Guizhou Province of China.
AB  - In this study, 68 group A streptococcus (GAS) isolates associated with two
      outbreaks of acute glomerulonephritis (AGN) in China were analyzed by emm typing.
      A total of 11 different emm types were identified. Analysis of emm type
      distribution suggested that AGN outbreaks in two counties were caused by emm60.1-
      and emm63.0-type GAS. These two types were further characterized by pulsed-field
      gel electrophoresis, multilocus sequence typing, sof sequence typing, and PCR
      based identification of streptococcal pyrogenic exotoxin A, B, and C (speA, speB,
      and speC) genes. In antimicrobial susceptibility tests, all outbreak strains were
      resistant to erythromycin and tetracycline, and the rates of resistance of
      nonoutbreak strains to the two antibiotics were 63.6% and 90.9%. This study is
      also the first to report a nephritogenic M63 GAS strain.

PMID- 19116349
TI  - Misidentification of a variant biotype of Escherichia coli O157:H7 as Escherichia
      fergusonii by Vitek 2 Compact.

PMID- 19116350
TI  - Sequence variation of human papillomavirus type 16 and measurement of viral
      integration by quantitative PCR.
AB  - Given that the integration of human papillomavirus type 16 (HPV16) into the host
      genome occurs preferentially with the disruption of the E2 gene, a ratio of E2 to
      E7 gene copies is often used as a marker for integration. It is largely
      undetermined, however, whether ratio estimates are affected by HPV intratypic
      variations. We assembled four plasmid constructs, each containing a DNA fragment
      from an HPV16 European, Asian-American, African-1, or African-2 variant. These
      constructs and nine cervical swab samples were assayed by real-time PCR with two
      primer-probe sets for each gene: a specific set, fully complementary to the HPV16
      prototype, and a degenerate set, incorporating degenerate bases at positions
      where nucleotides differed among the variants. The ratio of E2 to E7 gene copies
      for the European variant construct was close to 1, no matter which sets of
      primers and probes were used. While the ratios for the African-1 and Asian
      American variant constructs remained close to 1 with the degenerate sets of
      primers and probes, the ratios were 0.36 and 2.57, respectively, with the
      specific sets of primers and probes. In addition, a nucleotide alteration at the
      position immediately following the 3' end of the E2 forward primer binding site
      was found to be responsible for an underestimation of E2 gene copies for the
      African-2 variant construct. Similar patterns were found in nine cervical
      samples. In conclusion, mismatches between the primers and probes and their
      targets due to HPV16 intratypic variations would introduce errors in testing for
      integration; this situation can be sufficiently ameliorated by incorporating
      degenerate bases into the primers and probes.

PMID- 19116351
TI  - First case of Streptococcus oligofermentans endocarditis determined based on sodA
      gene sequences after amplification directly from valvular samples.
AB  - We report the first case of infection due to Streptococcus oligofermentans, which
      is a recently described oral Streptococcus species. It was responsible for the
      endocarditis and left forearm abscess of a 43-year-old woman. Identification was
      made using molecular techniques performed directly from valvular and surgical
      samples.

PMID- 19116352
TI  - Nucleic acid sequence-based amplification with oligochromatography for detection
      of Trypanosoma brucei in clinical samples.
AB  - Molecular tools, such as real-time nucleic acid sequence-based amplification
      (NASBA) and PCR, have been developed to detect Trypanosoma brucei parasites in
      blood for the diagnosis of human African trypanosomiasis (HAT). Despite good
      sensitivity, these techniques are not implemented in HAT control programs due to
      the high cost of the equipment, which is unaffordable for laboratories in
      developing countries where HAT is endemic. In this study, a simplified technique,
      oligochromatography (OC), was developed for the detection of amplification
      products of T. brucei 18S rRNA by NASBA. The T. brucei NASBA-OC test has
      analytical sensitivities of 1 to 10 parasites/ml on nucleic acids extracted from
      parasite culture and 10 parasites/ml on spiked blood. The test showed no reaction
      with nontarget pathogens or with blood from healthy controls. Compared to the
      composite standard applied in the present study, i.e., parasitological
      confirmation of a HAT case by direct microscopy or by microscopy after
      concentration of parasites using either a microhematocrit centrifugation
      technique or a mini-anion-exchange centrifugation technique, NASBA-OC on blood
      samples had a sensitivity of 73.0% (95% confidence interval, 60 to 83%), while
      standard expert microscopy had a sensitivity of 57.1% (95% confidence interval,
      44 to 69%). On cerebrospinal fluid samples, NASBA-OC had a sensitivity of 88.2%
      (95% confidence interval, 75 to 95%) and standard microscopy had a sensitivity of
      86.2% (95% confidence interval, 64 to 88%). The T. brucei NASBA-OC test developed
      in this study can be employed in field laboratories, because it does not require
      a thermocycler; a simple heat block or a water bath maintained at two different
      temperatures is sufficient for amplification.

PMID- 19116353
TI  - PCR-based quantitation and clonal diversity of the current prevalent invasive
      serogroup 6 pneumococcal serotype, 6C, in the United States in 1999 and 2006 to
      2007.
AB  - Following introduction of the 7-valent pneumococcal conjugate vaccine to the
      United States, rates of invasive pneumococcal disease (IPD) caused by serotype 6A
      declined among all age groups, while rates of IPD caused by newly identified
      serotype 6C increased slightly among persons 5 years of age and older.
      Conventionally serotyped 6A isolates (CS6As) from active population-based
      surveillance during 1999 and 2006 to 2007 were classified as serotypes 6A and 6C
      by an expedient and highly accurate serotype 6C-specific PCR assay developed
      during this study. PCR testing of 636 year 1999, 2006, and 2007 CS6As revealed 6C
      proportions of 35/214 (16.4%), 141/218 (64.7%), and 141/204 (69.1%),
      respectively. These results agreed with those from a previously devised
      monoclonal antibody-based serotyping system (346 CS6As compared). Type 6C IPD
      incidence significantly increased during 2006 and 2007 compared to during 1999
      (0.57 to 0.58 cases per 100,000 and 0.22 cases per 100,000, respectively; 164%
      increase from 1999 to 2007 [95% confidence interval, 87 to 270%]), while rates of
      IPD due to types 6A and 6B markedly decreased. In 2007, 31.2% of 6C isolates were
      not susceptible to penicillin. Serotype 6C is now the predominant serotype
      associated with serogroup 6 IPD in the United States and is often penicillin
      nonsusceptible. We performed multilocus sequence typing (MLST) on a limited
      sampling of 6C isolates with different antimicrobial susceptibility profiles.
      MLST of 42 6C isolates revealed 12 genotypes distributed among six distinct
      genetic groups. Fifteen 6C isolates shared one of four different MLST types with
      6C-negative CS6As. MLST results suggest 6C strains arose from independent
      recombination events involving only serotype 6A and 6C parental strains.

PMID- 19116354
TI  - Occurrence of spvA virulence gene and clinical significance for multidrug
      resistant Salmonella strains.
AB  - Nontyphoidal Salmonella strains are important reservoirs of antimicrobial
      resistance. An important issue that has not been investigated is whether the
      multiresistant Salmonella strains are more virulent than their susceptible
      counterparts. Salmonella isolates collected from clinical human (n=888) and
      porcine (n=2,120) cases at the same time period and geographic location were
      investigated. Antimicrobial susceptibility, PCR analysis for the spvA virulence
      gene, and pulsed-field gel electrophoresis (PFGE) genotyping were done. Carriage
      of spvA was associated with multidrug-resistant (MDR) type ACSSuT strains (odds
      ratio, 7.1; P<0.05), a type often implicated in bacteremic human cases. PFGE
      revealed that clinical isolates from pigs were more clonally related to those of
      human origin than the nonclinical porcine isolates. The findings suggest that MDR
      strains that also carry specific virulence factors are more likely to be of
      clinical significance.

PMID- 19116355
TI  - Evaluation of a highly sensitive qualitative human immunodeficiency virus type 1
      (HIV-1) RNA assay for detection of HIV-1 suppression.
AB  - By using a mathematical model, the APTIMA human immunodeficiency virus type 1
      (HIV-1) RNA qualitative assay was evaluated as a semiquantitative assay to
      distinguish HIV-1 patient samples needing quantitation from samples in which the
      virus was suppressed with antiretroviral therapy.

PMID- 19116356
TI  - Detection of viruses in human adenoid tissues by use of multiplex PCR.
AB  - By PCR, we detected a high frequency of viruses in adenoids obtained from
      children without acute respiratory symptoms. Our results suggest that
      persistent/latent viral infection in the respiratory tract confounds
      interpretation of the association of pathogen detection by PCR with acute
      respiratory infection in these sources.

PMID- 19116357
TI  - Necrotizing fasciitis caused by Haemophilus influenzae type b in an elderly
      patient.
AB  - Necrotizing fasciitis caused by Haemophilus influenzae type b is a rare infection
      of the skin and soft tissues. The only previously reported case involved a
      healthy infant. We report herein the case of an 81-year-old Japanese woman with
      diabetes mellitus who developed necrotizing fasciitis caused by H. influenzae
      type b.

PMID- 19116358
TI  - Characterization of a Canadian mink H3N2 influenza A virus isolate genetically
      related to triple reassortant swine influenza virus.
AB  - In 2007, an H3N2 influenza A virus was isolated from Canadian mink. This virus
      was found to be phylogenetically related to a triple reassortant influenza virus
      which emerged in Canadian swine in 2005, but it is antigenically distinct. The
      transmission of the virus from swine to mink seems to have occurred following the
      feeding of animals with a ration composed of uncooked meat by-products of swine
      obtained from slaughterhouse facilities. Serological analyses suggest that the
      mink influenza virus does not circulate in the swine population. Presently, the
      prevalence of influenza virus in Canadian farmed and wild mink populations is
      unknown. The natural occurrence of influenza virus infection in mink with the
      presence of clinical signs is a rare event that deserves to be reported.

PMID- 19116359
TI  - Cross-priming amplification for rapid detection of Mycobacterium tuberculosis in
      sputum specimens.
AB  - Cross-priming amplification (CPA) technology for tuberculosis diagnosis from
      sputum specimens was evaluated. The sensitivity of CPA from smear- and liquid
      culture-positive specimens was 96.9%, and that from smear-negative and liquid
      culture-positive specimens was 87.5%. The specificity of CPA in culture-negative
      specimens was 98.8%.

PMID- 19116360
TI  - Failure of cloxacillin in treatment of a patient with borderline oxacillin
      resistant Staphylococcus aureus endocarditis.
AB  - Clinical evidence for failure with beta-lactam therapy has been lacking for
      patients with borderline oxacillin-resistant Staphylococcus aureus (BORSA)
      infections. We describe a failure of cloxacillin for a patient with endocarditis
      due to BORSA. The isolate also had false-negative thermonuclease and coagulase
      test results.

PMID- 19116361
TI  - Activin-like kinase 5 (ALK5) mediates abnormal proliferation of vascular smooth
      muscle cells from patients with familial pulmonary arterial hypertension and is
      involved in the progression of experimental pulmonary arterial hypertension
      induced by monocrotaline.
AB  - Mutations in the gene for the transforming growth factor (TGF)-beta superfamily
      receptor, bone morphogenetic protein receptor II, underlie heritable forms of
      pulmonary arterial hypertension (PAH). Aberrant signaling via TGF-beta receptor
      I/activin receptor-like kinase 5 may be important for both the development and
      progression of PAH. We investigated the therapeutic potential of a well
      characterized and potent activin receptor-like kinase 5 inhibitor, SB525334 [6-(2
      tert-butyl-5-{6-methyl-pyridin-2-yl}-1H-imidazol-4-yl)-quinoxaline] for the
      treatment of PAH. In this study, we demonstrate that pulmonary artery smooth
      muscle cells from patients with familial forms of idiopathic PAH exhibit
      heightened sensitivity to TGF-beta1 in vitro, which can be attenuated after the
      administration of SB525334. We further demonstrate that SB525334 significantly
      reverses pulmonary arterial pressure and inhibits right ventricular hypertrophy
      in a rat model of PAH. Immunohistochemical studies confirmed a significant
      reduction in pulmonary arteriole muscularization induced by monocrotaline (used
      experimentally to induce PAH) after treatment of rats with SB525334.
      Collectively, these data are consistent with a role for the activin receptor-like
      kinase 5 in the progression of idiopathic PAH and imply that strategies to
      inhibit activin receptor-like kinase 5 signaling may have therapeutic benefit.

PMID- 19116362
TI  - Transmembrane interactions are needed for KAI1/CD82-mediated suppression of
      cancer invasion and metastasis.
AB  - In transmembrane (TM) domains, tetraspanin KAI1/CD82 contains an Asn, a Gln, and
      a Glu polar residue. A mutation of all three polar residues largely disrupts the
      migration-, invasion-, and metastasis-suppressive activities of KAI1/CD82.
      Notably, KAI1/CD82 inhibits the formation of microprotrusions and the release of
      microvesicles, while the mutation disrupts these inhibitions, revealing the
      connections of microprotrusion and microvesicle to KAI1/CD82 function. The TM
      polar residues are needed for proper interactions between KAI1/CD82 and
      tetraspanins CD9 and CD151, which also regulate cell movement, but not for the
      association between KAI1/CD82 and alpha3beta1 integrin. However, KAI1/CD82 still
      efficiently inhibits cell migration when either CD9 or CD151 is absent. Hence,
      KAI1/CD82 interacts with tetraspanin and integrin by different mechanisms and is
      unlikely to inhibit cell migration through its associated proteins. Moreover,
      without significantly affecting the glycosylation, homodimerization, and global
      folding of KAI1/CD82, the TM interactions maintain the conformational stability
      of KAI1/CD82, evidenced by the facts that the mutant is more sensitive to
      denaturation and less associable with tetraspanins and supported by the modeling
      analysis. Thus, the TM interactions mediated by these polar residues determine a
      conformation either in or near the tightly packed TM region and this conformation
      and/or its change are needed for the intrinsic activity of KAI1/CD82. In contrast
      to immense efforts to block the signaling of cancer progression, the perturbation
      of TM interactions may open a new avenue to prevent cancer invasion and
      metastasis.

PMID- 19116363
TI  - Massive T-lymphocyte infiltration into the host stroma is essential for
      fibroblast growth factor-2-promoted growth and metastasis of mammary tumors via
      neovascular stability.
AB  - Inflammation in the tumor stroma greatly influences tumor development. In the
      present study, we investigated the roles of fibroblast growth factor (FGF)-2
      induced chronic inflammation in the development of 4T1 murine mammary tumors.
      Administration of FGF-2 into the tumor inoculation site during the initial phase
      of tumor growth enhanced tumor growth and pulmonary metastasis as well as
      microvessel density in tumor tissues in normal but not in nude mice. Infiltration
      of T lymphocytes and macrophages, recruitment of pericytes/vascular mural cells
      in neovascular walls, and the expression levels of cyclooxygenase (COX)-2 and
      vascular endothelial growth factor A (VEGFA) were also enhanced in the FGF-2
      activated host stroma of normal mice. In addition, FGF-2-induced tumor growth and
      metastasis was abrogated by administration of either an immunosuppressant, FK506,
      or a COX-2 inhibitor. FGF-2 enhanced prostaglandin E(2) secretion in cultured T
      lymphocytes. In addition, VEGFA secretion was increased in a co-culture of T
      lymphocytes and fibroblasts in vitro. These results indicate that the massive
      infiltration of T lymphocytes into FGF-2-activated host stroma during the initial
      phase of tumor growth enhances neovascular stability by regulating endogenous COX
      2 and VEGFA levels because both compounds are known to play important roles in
      marked 4T1 mammary tumor development via FGF-2-induced inflammatory reactions.

PMID- 19116364
TI  - A protein kinase Cdelta-dependent protein kinase D pathway modulates ERK1/2 and
      JNK1/2 phosphorylation and Bim-associated apoptosis by asbestos.
AB  - Inhalation of asbestos and oxidant-generating pollutants causes injury and
      compensatory proliferation of lung epithelium, but the signaling mechanisms that
      lead to these responses are unclear. We hypothesized that a protein kinase
      (PK)Cdelta-dependent PKD pathway was able to regulate downstream mitogen
      activated protein kinases, affecting pro- and anti-apoptotic responses to
      asbestos. Elevated levels of phosphorylated PKD (p-PKD) were observed in distal
      bronchiolar epithelial cells of mice inhaling asbestos. In contrast, PKCdelta-/-
      mice showed significantly lower levels of p-PKD in lung homogenates and in situ
      after asbestos inhalation. In a murine lung epithelial cell line, asbestos caused
      significant increases in the phosphorylation of PKCdelta-dependent PKD, ERK1/2,
      and JNK1/2/c-Jun that occurred with decreases in the BH3-only pro-apoptotic
      protein, Bim. Silencing of PKCdelta, PKD, and use of small molecule inhibitors
      linked the ERK1/2 pathway to the prevention of Bim-associated apoptosis as well
      as the JNK1/2/c-Jun pathway to the induction of apoptosis. Our studies are the
      first to show that asbestos induces PKD phosphorylation in lung epithelial cells
      both in vivo and in vitro. PKCdelta-dependent PKD phosphorylation by asbestos is
      causally linked to a cellular pathway that involves the phosphorylation of both
      ERK1/2 and JNK1/2, which play opposing roles in the apoptotic response induced by
      asbestos.

PMID- 19116365
TI  - Glycinergic innervation of motoneurons is deficient in amyotrophic lateral
      sclerosis mice: a quantitative confocal analysis.
AB  - Altered motoneuron excitability is involved in amyotrophic lateral sclerosis
      pathobiology. To test the hypothesis that inhibitory interneuron innervation of
      spinal motoneurons is abnormal in an amyotrophic lateral sclerosis mouse model,
      we measured GABAergic, glycinergic, and cholinergic immunoreactive terminals on
      spinal motoneurons in mice expressing a mutant form of human superoxide dismutase
      1 with a Gly93-->Ala substitution (G93A-SOD1) and in controls at different ages.
      Glutamic acid decarboxylase, glycine transporter-2, and choline acetyltransferase
      were used as markers for GABAergic, glycinergic, and cholinergic terminals,
      respectively. Triple immunofluorescent labeling of boutons contacting motoneurons
      was visualized by confocal microscopy and analyzed quantitatively. Glycine
      transporter-2-bouton density on lateral motoneurons was decreased significantly
      in G93A-SOD1 mice compared with controls. This reduction was absent at 6 weeks of
      age but present in asymptomatic 8-week-old mice and worsened with disease
      progression from 12 to 14 weeks of age. Motoneurons lost most glycinergic
      innervation by 16 weeks of age (end-stage) when there was a significant decrease
      in the numbers of motoneurons and choline acetyltransferase-positive boutons. No
      significant differences in glutamic acid decarboxylase-bouton densities were
      found in G93A-SOD1 mice. Reduction of glycinergic innervation preceded
      mitochondrial swelling and vacuolization. Calbindin-positive Renshaw cell number
      was decreased significantly at 12 weeks of age in G93A-SOD1 mice. Thus, either
      the selective loss of inhibitory glycinergic regulation of motoneuron function or
      glycinergic interneuron degeneration contributes to motoneuron degeneration in
      amyotrophic lateral sclerosis.

PMID- 19116366
TI  - A defective SERCA1 protein is responsible for congenital pseudomyotonia in
      Chianina cattle.
AB  - Recently, a muscular disorder defined as "congenital pseudomyotonia" was
      described in Chianina cattle, one of the most important Italian cattle breeds for
      quality meat and leather. The clinical phenotype of this disease is characterized
      by an exercise-induced muscle contracture that prevents animals from performing
      muscular activities. On the basis of clinical symptoms, Chianina pseudomyotonia
      appeared related to human Brody's disease, a rare inherited disorder of skeletal
      muscle function that results from a sarcoplasmic reticulum Ca(2+)-ATPase (SERCA1)
      deficiency caused by a defect in the ATP2A1 gene that encodes SERCA1. SERCA1 is
      involved in transporting calcium from the cytosol to the lumen of the
      sarcoplasmic reticulum. Recently, we identified the genetic defect underlying
      Chianina cattle pseudomyotonia. A missense mutation in exon 6 of the ATP2A1 gene,
      leading to an R164H substitution in the SERCA1 protein, was found. In this study,
      we provide biochemical evidence for a selective deficiency in SERCA1 protein
      levels in sarcoplasmic reticulum membranes from affected muscles, although mRNA
      levels are unaffected. The reduction of SERCA1 levels accounts for the reduced
      Ca(2+)-ATPase activity without any significant change in Ca(2+)-dependency. The
      loss of SERCA1 is not compensated for by the expression of the SERCA2 isoform. We
      believe that Chianina cattle pseudomyotonia might, therefore, be the true
      counterpart of human Brody's disease, and that bovine species might be used as a
      suitable animal model.

PMID- 19116367
TI  - Co-existent pseudoxanthoma elasticum and vitamin K-dependent coagulation factor
      deficiency: compound heterozygosity for mutations in the GGCX gene.
AB  - Pseudoxanthoma elasticum (PXE) is a multisystem disorder characterized by ectopic
      mineralization of connective tissues with primary manifestations in the skin,
      eyes, and cardiovascular system. The classic forms of PXE are due to mutations in
      the ABCC6 gene that encodes the ABCC6 protein, a putative transmembrane
      transporter expressed primarily in the liver and the kidneys. PXE-like clinical
      findings have been encountered in association with vitamin K-dependent
      coagulation factor deficiency, an autosomal recessive disorder that is due to
      mutations in either the GGCX or VKORC1 genes. In this study, we investigated a
      family with two siblings with characteristic features of PXE and vitamin K
      dependent coagulation factor deficiency. Mutation analysis identified two GGCX
      mutations in the affected individuals (p. R83W and p.Q374X); however, no
      mutations in either ABCC6 or VKORC1 could be found. GGCX encodes a gamma-glutamyl
      carboxylase necessary for activation of both coagulation factors in the liver and
      matrix gla protein, which, in fully carboxylated form, is able to prevent ectopic
      mineralization. Analysis of skin by specific antibodies demonstrated that matrix
      gla protein was found predominantly in undercarboxylated form and was associated
      with the mineralized areas in the patients' lesional skin. These observations
      pathomechanistically suggest that, in our patients, reduced carboxylase activity
      results in a reduction of matrix gla protein carboxylation, thus allowing
      peripheral mineralization to occur. Our findings also confirm GGCX as the second
      gene locus causing PXE.

PMID- 19116369
TI  - Are angiotensin II receptor antagonists useful strategies in steatotic and
      nonsteatotic livers in conditions of partial hepatectomy under ischemia
      reperfusion?
AB  - We examined whether angiotensin (Ang) II receptor antagonists could be considered
      a therapeutic strategy in steatotic and nonsteatotic livers in conditions of
      partial hepatectomy under ischemia-reperfusion (I/R), which is commonly applied
      in clinical practice to reduce blood loss. We report that Ang II type I receptor
      (AT1R) antagonist, but not Ang II type II receptor (AT2R) antagonist, increased
      regeneration in nonsteatotic livers. In the presence of steatosis, both AT1R and
      AT2R antagonists increased liver regeneration. This effect was stronger when the
      two were combined. Neither of the Ang II receptor antagonists protected
      nonsteatotic livers against damage. Only the AT1R antagonist, through nitric
      oxide inhibition, reduced damage in steatotic livers. The combination of the AT1R
      and AT2R antagonists in steatotic livers conferred a similar degree of protection
      to AT1R antagonist alone. Herein, we show that p38 mitogen-activated protein
      kinase (p38) was a key mechanism in the regeneration induced by the Ang II
      receptor antagonists in both liver types because when this signaling pathway was
      inhibited, the beneficial effects of the Ang II receptor antagonists on liver
      regeneration disappeared, regardless of hepatocyte growth factor or transforming
      growth factor beta-hepatic levels. In conclusion, in conditions of partial
      hepatectomy under I/R, the AT1R antagonist for nonsteatotic livers and the AT1R
      and AT2R antagonists for steatotic livers improved regeneration in the remnant
      liver through p38 activation. In addition, the combination of the AT1R and AT2R
      antagonists in steatotic livers led to stronger liver regeneration than either
      antagonists used separately and also provided the same protection against damage
      as that afforded by AT1R antagonist alone.

PMID- 19116368
TI  - Collagen fragmentation promotes oxidative stress and elevates matrix
      metalloproteinase-1 in fibroblasts in aged human skin.
AB  - Aged human skin is fragile because of fragmentation and loss of type I collagen
      fibrils, which confer strength and resiliency. We report here that dermal
      fibroblasts express increased levels of collagen-degrading matrix
      metalloproteinases-1 (MMP-1) in aged (>80 years old) compared with young (21 to
      30 years old) human skin in vivo. Transcription factor AP-1 and alpha2beta1
      integrin, which are key regulators of MMP-1 expression, are also elevated in
      fibroblasts in aged human skin in vivo. MMP-1 treatment of young skin in organ
      culture causes fragmentation of collagen fibrils and reduces fibroblast stretch,
      consistent with reduced mechanical tension, as observed in aged human skin.
      Limited fragmentation of three-dimensional collagen lattices with exogenous MMP-1
      also reduces fibroblast stretch and mechanical tension. Furthermore, fibroblasts
      cultured in fragmented collagen lattices express elevated levels of MMP-1, AP-1,
      and alpha2beta1 integrin. Importantly, culture in fragmented collagen raises
      intracellular oxidant levels and treatment with antioxidant MitoQ(10)
      significantly reduces MMP-1 expression. These data identify positive feedback
      regulation that couples age-dependent MMP-1-catalyzed collagen fragmentation and
      oxidative stress. We propose that this self perpetuating cycle promotes human
      skin aging. These data extend the current understanding of the oxidative theory
      of aging beyond a cellular-centric view to include extracellular matrix and the
      critical role that connective tissue microenvironment plays in the biology of
      aging.

PMID- 19116370
TI  - Roles of inner blood-retinal barrier organic anion transporter 3 in the
      vitreous/retina-to-blood efflux transport of p-aminohippuric acid,
      benzylpenicillin, and 6-mercaptopurine.
AB  - The purpose of the present study was to characterize rat organic anion
      transporter (Oat) 3 (Oat3, Slc22a8) in the efflux transport at the inner blood
      retinal barrier (BRB). Reverse transcription-polymerase chain reaction analysis
      showed that rat (r) Oat3 mRNA is expressed in retinal vascular endothelial cells
      (RVECs), but not rOat1 and rOat2 mRNA. The expression of Oat3 in the retina and
      human cultured retinal endothelial cells was further confirmed by Western blot
      analysis. Immunohistochemical staining in RVECs showed that rOat3 is colocalized
      with glucose transporter 1, but not P-glycoprotein, suggesting that rOat3 is
      possibly located at the abluminal membrane of the RVEC. The contribution of rOat3
      to the efflux of [(3)H]p-aminohippuric acid ([(3)H]PAH), [(3)H]benzylpenicillin
      ([(3)H]PCG), and [(14)C]6-mercaptopurine ([(14)C]6-MP), substrates of rOat3, from
      the vitreous humor/retina to the circulating blood across the inner BRB was
      evaluated using the microdialysis method. [(3)H]PAH, [(3)H]PCG, [(14)C]6-MP, and
      [(14)C] or [(3)H]d-mannitol, a bulk flow marker, were biexponentially eliminated
      from the vitreous humor after vitreous bolus injection. The elimination rate
      constant of [(3)H]PAH, [(3)H]PCG, and [(14)C]6-MP during the terminal phase was
      approximately 2-fold greater than that of d-mannitol. This efflux transport was
      reduced in the retinal presence of probenecid, PAH, and PCG, whereas it was not
      inhibited by digoxin. In conclusion, rOat3 is expressed at the inner BRB and
      involved in the vitreous humor/retina-to-blood transport of PAH, PCG, and 6-MP.
      This transport system is one mechanism to limit the retinal distribution of PAH,
      PCG, and 6-MP.

PMID- 19116371
TI  - Beyond triglyceride synthesis: the dynamic functional roles of MGAT and DGAT
      enzymes in energy metabolism.
AB  - Monoacyglycerol acyltransferases (MGATs) and diacylglycerol acyltransferases
      (DGATs) catalyze two consecutive steps of enzyme reactions in the synthesis of
      triacylglycerols (TAGs). The metabolic complexity of TAG synthesis is reflected
      by the presence of multiple isoforms of MGAT and DGAT enzymes that differ in
      catalytic properties, subcellular localization, tissue distribution, and
      physiological functions. MGAT and DGAT enzymes play fundamental roles in the
      metabolism of monoacylglycerol (MAG), diacylglycerol (DAG), and triacylglycerol
      (TAG) that are involved in many aspects of physiological functions, such as
      intestinal fat absorption, lipoprotein assembly, adipose tissue formation, signal
      transduction, satiety, and lactation. The recent progress in the phenotypic
      characterization of mice deficient in MGAT and DGAT enzymes and the development
      of chemical inhibitors have revealed important roles of these enzymes in the
      regulation of energy homeostasis and insulin sensitivity. Consequently, selective
      inhibition of MGAT or DGAT enzymes by synthetic compounds may provide novel
      treatment for obesity and its related metabolic complications.

PMID- 19116373
TI  - Benefits and limitations of reducing glucagon action for the treatment of type 2
      diabetes.
AB  - Glucagon is secreted from the alpha-cells of the pancreatic islets and regulates
      glucose homeostasis through modulation of hepatic glucose production. As elevated
      glucagon levels contribute to the pathophysiology of hyperglycemia in subjects
      with type 2 diabetes, reduction of glucagon receptor gene (Gcgr) activity
      represents a potential target for the treatment of T2DM. Herein, we review
      current concepts of glucagon action in hepatic and extrahepatic tissues and
      evaluate the therapeutic potential, mechanisms of action, and safety of reducing
      Gcgr signaling for the treatment of T2DM.

PMID- 19116372
TI  - The genetics of neutral lipid biosynthesis: an evolutionary perspective.
AB  - The storage of fatty acids and fatty alcohols in the form of neutral lipids such
      as triacylglycerol (TAG), cholesteryl ester (CE), and wax ester (WE) serves to
      provide reservoirs for membrane formation and maintenance, lipoprotein
      trafficking, lipid detoxification, evaporation barriers, and fuel in times of
      stress or nutrient deprivation. This ancient process likely originated in
      actinomycetes and has persisted in eukaryotes, albeit by different molecular
      mechanisms. A surfeit of neutral lipids is strongly, perhaps causally, related to
      several human diseases such as diabetes mellitus, obesity, atherosclerosis and
      nonalcoholic fatty liver disease. Therefore, understanding the metabolic pathways
      of neutral lipid synthesis and the roles of the enzymes involved may facilitate
      the development of new therapeutic interventions for these syndromes.

PMID- 19116374
TI  - 3,5-Diiodo-L-thyronine rapidly enhances mitochondrial fatty acid oxidation rate
      and thermogenesis in rat skeletal muscle: AMP-activated protein kinase
      involvement.
AB  - Triiodothyronine regulates energy metabolism and thermogenesis. Among
      triiodothyronine derivatives, 3,5-diiodo-l-thyronine (T(2)) has been shown to
      exert marked effects on energy metabolism by acting mainly at the mitochondrial
      level. Here we investigated the capacity of T(2) to affect both skeletal muscle
      mitochondrial substrate oxidation and thermogenesis within 1 h after its
      injection into hypothyroid rats. Administration of T(2) induced an increase in
      mitochondrial oxidation when palmitoyl-CoA (+104%), palmitoylcarnitine (+80%), or
      succinate (+30%) was used as substrate, but it had no effect when pyruvate was
      used. T(2) was able to 1) activate the AMPK-ACC-malonyl-CoA metabolic signaling
      pathway known to direct lipid partitioning toward oxidation and 2) increase the
      importing of fatty acids into the mitochondrion. These results suggest that T(2)
      stimulates mitochondrial fatty acid oxidation by activating several metabolic
      pathways, such as the fatty acid import/beta-oxidation cycle/FADH(2)-linked
      respiratory pathways, where fatty acids are imported. T(2) also enhanced skeletal
      muscle mitochondrial thermogenesis by activating pathways involved in the
      dissipation of the proton-motive force not associated with ATP synthesis ("proton
      leak"), the effect being dependent on the presence of free fatty acids inside
      mitochondria. We conclude that skeletal muscle is a target for T(2), and we
      propose that, by activating processes able to enhance mitochondrial fatty acid
      oxidation and thermogenesis, T(2) could play a role in protecting skeletal muscle
      against excessive intramyocellular lipid storage, possibly allowing it to avoid
      functional disorders.

PMID- 19116376
TI  - Noninvasive assessment of pancreatic beta-cell function in vivo with manganese
      enhanced magnetic resonance imaging.
AB  - Loss of beta-cell function in type 1 and type 2 diabetes leads to metabolic
      dysregulation and inability to maintain normoglycemia. Noninvasive imaging of
      beta-cell function in vivo would therefore provide a valuable diagnostic and
      research tool for quantifying progression to diabetes and response to therapeutic
      intervention. Because manganese (Mn(2+)) is a longitudinal relaxation time (T1)
      shortening magnetic resonance imaging (MRI) contrast agent that enters cells such
      as pancreatic beta-cells through voltage-gated calcium channels, we hypothesized
      that Mn(2+)-enhanced MRI of the pancreas after glucose infusion would allow for
      noninvasive detection of beta-cell function in vivo. To test this hypothesis, we
      administered glucose and saline challenges intravenously to normal mice and mice
      given high or low doses of streptozotocin (STZ) to induce diabetes. Serial
      inversion recovery MRI was subsequently performed after Mn(2+) injection to probe
      Mn(2+) accumulation in the pancreas. Time-intensity curves of the pancreas
      (normalized to the liver) fit to a sigmoid function showed a 51% increase in
      signal plateau height after glucose stimulation relative to saline (P < 0.01) in
      normal mice. In diabetic mice given a high dose of STZ, only a 9% increase in
      plateau signal intensity was observed after glucose challenge (P = not
      significant); in mice given a low dose of STZ, a 20% increase in plateau signal
      intensity was seen after glucose challenge (P = 0.02). Consistent with these
      imaging findings, the pancreatic insulin content of high- and low-dose STZ
      diabetic mice was reduced about 20-fold and 10-fold, respectively, compared with
      normal mice. We conclude that Mn(2+)-enhanced MRI demonstrates excellent
      potential as a means for noninvasively monitoring beta-cell function in vivo and
      may have the sensitivity to detect progressive decreases in function that occur
      in the diabetic disease process.

PMID- 19116377
TI  - Effects of critical illness and organ failure on therapeutic argatroban dosage
      requirements in patients with suspected or confirmed heparin-induced
      thrombocytopenia.
AB  - BACKGROUND: Critically ill patients often require therapeutic argatroban dosages
      lower than those recommended in package labeling. The magnitude of dosage
      alteration in relation to severity of organ failure is unknown. OBJECTIVE: To
      compare therapeutic argatroban dosages between critically ill and noncritically
      ill patients with confirmed or suspected heparin-induced thrombocytopenia and
      investigate the relationship between total Sequential Organ Failure Assessment
      (SOFA) score and therapeutic argatroban dosage. METHODS: This retrospective
      cohort study was conducted at an urban academic medical center. Adults without
      Child-Pugh class C hepatic dysfunction who received argatroban for more than 24
      hours over a 3-year period were included. Therapeutic argatroban dosage was that
      resulting in 2 consecutive activated partial thromboplastin time (aPTT) values
      1.5-3 times the patient-specific baseline obtained at least 4 hours apart.
      Initial argatroban dosages were at the discretion of the managing service.
      RESULTS: Fifty-three patients (critically ill, n = 34; noncritically ill, n = 19)
      were included. Critically ill patients had higher median [interquartile range]
      Acute Physiology and Chronic Health Evaluation (APACHE II) (17 [12-21] vs 10
      [3.25-17.75]; p = 0.007) and SOFA (11 [7-13] vs 2 [0-2.75]; p < 0.001) scores.
      Critically ill patients required lower mean +/- SD therapeutic argatroban dosage
      (0.6 +/- 0.5 vs 1.4 +/- 0.9 microg/kg/min; p < 0.001). There was no significant
      difference in time to therapeutic aPTT or proportion of aPTTs within therapeutic
      range. Argatroban dosage was inversely related to SOFA score tertiles (<6: 1.34
      +/- 0.82 microg/kg/min; 6-9: 0.93 +/- 0.54; > or =10: 0.40 +/- 0.27; p < 0.001).
      Total SOFA score at the time of argatroban initiation was independently
      associated with an argatroban dosage less than 0.75 microg/kg/min (OR 1.5, 95% CI
      1.2 to 1.8; p < 0.001). Adverse events were similar between groups. CONCLUSIONS:
      Critically ill patients with single or multiple organ failure require lower
      therapeutic argatroban dosages compared with noncritically ill patients. Because
      of an inverse relationship with SOFA score, initial argatroban dosage in
      critically ill patients should be based on the presence and magnitude of organ
      failure.

PMID- 19116375
TI  - Hypothalamic proinflammatory lipid accumulation, inflammation, and insulin
      resistance in rats fed a high-fat diet.
AB  - Weight gain induced by an energy-dense diet is hypothesized to arise in part from
      defects in the neuronal response to circulating adiposity negative feedback
      signals, such as insulin. Peripheral tissue insulin resistance involves cellular
      inflammatory responses thought to be invoked by excess lipid. Therefore, we
      sought to determine whether similar signaling pathways are activated in the brain
      of rats fed a high-fat (HF) diet. The ability of intracerebroventricular (icv)
      insulin to reduce food intake and activate hypothalamic signal transduction is
      attenuated in HF-fed compared with low-fat (LF)-fed rats. This effect was
      accompanied by both hypothalamic accumulation of palmitoyl- and stearoyl-CoA and
      activation of a marker of inflammatory signaling, inhibitor of kappaB kinase-beta
      (IKKbeta). Hypothalamic insulin resistance and inflammation were observed with
      icv palmitate infusion or HF feeding independent of excess caloric intake. Last,
      we observed that central IKKbeta inhibition reduced food intake and was
      associated with increased hypothalamic insulin sensitivity in rats fed a HF but
      not a LF diet. These data collectively support a model of diet-induced obesity
      whereby dietary fat, not excess calories, induces hypothalamic insulin resistance
      by increasing the content of saturated acyl-CoA species and activating local
      inflammatory signals, which result in a failure to appropriately regulate food
      intake.

PMID- 19116378
TI  - Risk of fractures with selective serotonin-reuptake inhibitors or tricyclic
      antidepressants.
AB  - OBJECTIVE: To evaluate the literature associating the risk of fracture during
      antidepressant therapy. DATA SOURCES: Literature was identified via MEDLINE (1970
      August 2008) using the search terms selective serotonin-reuptake inhibitors,
      tricyclic antidepressants, antidepressants, and fracture. Reference citations
      from publications identified were also reviewed. All articles in English
      identified from the data sources were evaluated. DATA SYNTHESIS: Selective
      serotonin-reuptake inhibitors (SSRIs) are generally prescribed over other classes
      of antidepressants because they are considered to be relatively safer. Recent
      evidence, however, suggests that SSRIs may be associated with an increased risk
      of fractures. Thirteen clinical studies were identified in the literature search
      (7 case controls, 5 prospective cohorts, 1 cross-sectional). Most studies
      compared SSRIs with tricyclic antidepressants (TCAs) and found similar or greater
      risk of fracture associated with use of an SSRI. This risk appeared to be highest
      at the beginning of therapy with TCAs and eventually diminished. SSRI risk tended
      to increase slightly over time. No risk was seen with other classes of
      antidepressants. However, the number of patients using antidepressants was low.
      CONCLUSIONS: There may be a possible correlation with SSRI or TCA use and risk of
      fracture. Prospective, randomized controlled trials with sufficient patient
      samples are needed to verify this finding.

PMID- 19116380
TI  - From human to mouse and back: 'tumorgraft' models surge in popularity.

PMID- 19116379
TI  - Cisplatin and oxaliplatin toxicity: importance of cochlear kinetics as a
      determinant for ototoxicity.
AB  - BACKGROUND: Cisplatin is a cornerstone anticancer drug with pronounced
      ototoxicity, whereas oxaliplatin, a platinum derivative with a different clinical
      profile, is rarely ototoxic. This difference has not been explained. METHODS: In
      HCT-116 cells, cisplatin (20 microM)-induced apoptosis was reduced by a calcium
      chelator from 9.9-fold induction (95% confidence interval [CI] = 8.1- to 11.7
      fold), to 3.1-fold induction (95% CI = 2.0- to 4.2-fold) and by superoxide
      scavenging from 9.3-fold (95% CI = 8.8- to 9.8-fold), to 5.1-fold (95% CI = 4.4-
      to 5.8-fold). A guinea pig model (n = 23) was used to examine pharmacokinetics.
      Drug concentrations were determined by liquid chromatography with post-column
      derivatization. The total platinum concentration in cochlear tissue was
      determined by inductively coupled plasma mass spectrometry. Drug pharmacokinetics
      was assessed by determining the area under the concentration-time curve (AUC).
      Statistical tests were two-sided. RESULTS: In HCT-116 cells, cisplatin (20
      microM)-induced apoptosis was reduced by a calcium chelator from 9.9-fold
      induction (95% confidence interval [CI] = 8.1- to 11.7-fold to 3.1-fold
      induction) (95% CI = 2.0- to 4.2-fold) and by superoxide scavenging (from 9.3
      fold, 95% CI = 8.8- to 9.8-fold, to 5.1-fold, 95% CI = 4.4- to 5.8-fold).
      Oxaliplatin (20 microM)-induced apoptosis was unaffected by calcium chelation
      (from 7.1- to 6.2-fold induction) and by superoxide scavenging (from 5.9- to 5.6
      fold induction). In guinea pig cochlea, total platinum concentration (0.12 vs
      0.63 microg/kg, respectively, P = .008) and perilymphatic drug concentrations
      (238 vs 515 microM x minute, respectively, P < .001) were lower after intravenous
      oxaliplatin treatment (16.6 mg/kg) than after equimolar cisplatin treatment (12.5
      mg/kg). However, after a non-ototoxic cisplatin dose (5 mg/kg) or the same
      oxaliplatin dose (16.6 mg/kg), the AUC for perilymphatic concentrations was
      similar, indicating that the two drugs have different cochlear pharmacokinetics.
      CONCLUSION: Cisplatin- but not oxaliplatin-induced apoptosis involved superoxide
      related pathways. Lower cochlear uptake of oxaliplatin than cisplatin appears to
      be a major explanation for its lower ototoxicity.

PMID- 19116381
TI  - StatBite: Cervical cancer mortality in Nordic countries.

PMID- 19116383
TI  - Anti-epithelial cell adhesion molecule antibodies and the detection of
      circulating normal-like breast tumor cells.
AB  - Identification of specific subtypes of circulating tumor cells in peripheral
      blood of cancer patients can provide information about the biology of metastasis
      and improve patient management. However, to be effective, the method used to
      identify circulating tumor cells must detect all tumor cell types. We
      investigated whether the five subtypes of human breast cancer cells that have
      been defined by global gene expression profiling-normal-like, basal, HER2
      positive, and luminal A and B-were identified by CellSearch, a US Food and Drug
      Administration-approved test that uses antibodies against the cell surface
      expressed epithelial cell adhesion molecule (EpCAM) to isolate circulating tumor
      cells. We used global gene expression profiling to determine the subtypes of a
      well-defined panel of 34 human breast cancer cell lines (15 luminal, nine normal
      like, five basal-like, and five Her2-positive). We mixed 50-150 cells from 10 of
      these cell lines with 7.5 mL of blood from a single healthy human donor, and the
      mixtures were subjected to the CellSearch test to isolate the breast cancer
      cells. We found that the CellSearch isolation method, which uses EpCAM on the
      surface of circulating tumor cells for cell isolation, did not recognize, in
      particular, normal-like breast cancer cells, which in general have aggressive
      features. New tests that include antibodies that specifically recognize normal
      like breast tumor cells but not cells of hematopoietic origin are needed.

PMID- 19116382
TI  - Insulin, insulin-like growth factor-I, and risk of breast cancer in
      postmenopausal women.
AB  - BACKGROUND: The positive association between obesity and postmenopausal breast
      cancer has been attributed, in part, to the fact that estrogen, a risk factor for
      breast cancer, is synthesized in adipose tissue. Obesity is also associated with
      high levels of insulin, a known mitogen. However, no prospective studies have
      directly assessed associations between circulating levels of insulin and/or
      insulin-like growth factor (IGF)-I, a related hormone, and the risk of breast
      cancer independent of estrogen level. METHODS: We conducted a case-cohort study
      of incident breast cancer among nondiabetic women who were enrolled in the
      Women's Health Initiative Observational Study (WHI-OS), a prospective cohort of
      93,676 postmenopausal women. Fasting serum samples obtained at study entry from
      835 incident breast cancer case subjects and from a subcohort of 816 randomly
      chosen WHI-OS subjects were tested for levels of insulin, glucose, total IGF-I,
      free IGF-I, insulin-like growth factor binding protein-3, and estradiol.
      Multivariable Cox proportional hazards models were used to estimate associations
      between levels of the serologic factors and baseline characteristics (including
      body mass index [BMI]) and the risk of breast cancer. All statistical tests were
      two-sided. Results Insulin levels were positively associated with the risk of
      breast cancer (hazard ratio [HR] for highest vs lowest quartile of insulin level
      = 1.46, 95% confidence interval [CI] = 1.00 to 2.13, P(trend) = .02); however,
      the association with insulin level varied by hormone therapy (HT) use
      (P(interaction) = .01). In a model that controlled for multiple breast cancer
      risk factors including estradiol, insulin level was associated with breast cancer
      only among nonusers of HT (HR for highest vs lowest quartile of insulin level =
      2.40, 95% CI = 1.30 to 4.41, P(trend) < .001). Obesity (BMI >or=30 kg/m(2)) was
      also associated with the risk of breast cancer among nonusers of HT (HR for BMI
      >or=30 kg/m(2) vs 18.5 to <25 kg/m(2) = 2.12, 95% CI = 1.26 to 3.58, P(trend) =
      .003); however, this association was attenuated by adjustment for insulin
      (P(trend) = .40). CONCLUSION: These data suggest that hyperinsulinemia is an
      independent risk factor for breast cancer and may have a substantial role in
      explaining the obesity-breast cancer relationship.

PMID- 19116384
TI  - Biomarker studies abound for early detection of lung cancer.

PMID- 19116385
TI  - Re: 'A threefold dose intensity treatment with ifosfamide, carboplatin, and
      etoposide for patients with small-cell lung cancer: a randomized trial'.

PMID- 19116386
TI  - Urine biomarkers may someday detect even distant tumors.

PMID- 19116387
TI  - Vitamin supplements and cancer prevention: where do randomized controlled trials
      stand?

PMID- 19116388
TI  - A field synopsis on low-penetrance variants in DNA repair genes and cancer
      susceptibility.
AB  - BACKGROUND: Several genes encoding for DNA repair molecules implicated in
      maintaining genomic integrity have been proposed as cancer-susceptibility genes.
      Although efforts have been made to create synopses for specific fields that
      summarize the data from genetic association studies, such an overview is not
      available for genes involved in DNA repair. METHODS: We have created a regularly
      updated database of studies addressing associations between DNA repair gene
      variants (excluding highly penetrant mutations) and different types of cancer.
      Using 1087 datasets and publicly available data from genome-wide association
      platforms, meta-analyses using dominant and recessive models were performed on
      241 associations between individual variants and specific cancer types that had
      been tested in two or more independent studies. The epidemiological strength of
      each association was graded with Venice criteria that assess amount of evidence,
      replication, and protection from bias. All statistical tests were two-sided.
      RESULTS: Thirty-one nominally statistically significant (ie, P < .05 without
      adjustment for multiple comparisons) associations were recorded for 16 genes in
      dominant and/or recessive model analyses (BRCA2, CCND1, ERCC1, ERCC2, ERCC4,
      ERCC5, MGMT, NBN, PARP1, POLI, TP53, XPA, XRCC1, XRCC2, XRCC3, and XRCC4). XRCC1,
      XRCC2, TP53, and ERCC2 variants were each nominally associated with several types
      of cancer. Three associations were graded as having "strong" credibility, another
      four had modest credibility, and 24 had weak credibility based on Venice
      criteria. Requiring more stringent P values to account for multiplicity of
      comparisons, only the associations of ERCC2 codon 751 (recessive model) and of
      XRCC1 -77 T>C (dominant model) with lung cancer had P <or= .0001 and retained P
      <or= .001 even when the first published studies on the respective associations
      were excluded. CONCLUSIONS: We have conducted meta-analyses of 241 associations
      between variants in DNA repair genes and cancer and have found sparse association
      signals with strong epidemiological credibility. This synopsis offers a model to
      survey the current status and gaps in evidence in the field of DNA repair genes
      and cancer susceptibility, may indicate potential pleiotropic activity of genes
      and gene pathways, and may offer mechanistic insights in carcinogenesis.

PMID- 19116389
TI  - Vitamins C and E and beta carotene supplementation and cancer risk: a randomized
      controlled trial.
AB  - BACKGROUND: Observational studies suggested that a diet high in fruits and
      vegetables, both of which are rich with antioxidants, may prevent cancer
      development. However, findings from randomized trials of the association between
      antioxidant use and cancer risk have been mostly negative. METHODS: From 8171
      women who were randomly assigned in the Women's Antioxidant Cardiovascular Study,
      a double-blind, placebo-controlled 2 x 2 x 2 factorial trial of vitamin C (500 mg
      of ascorbic acid daily), natural-source vitamin E (600 IU of alpha-tocopherol
      every other day), and beta carotene (50 mg every other day), 7627 women who were
      free of cancer before random assignment were selected for this study. Diagnoses
      and deaths from cancer at a specific site were confirmed by use of hospital
      reports and the National Death Index. Cox proportional hazards regression models
      were used to assess hazard ratios (represented as relative risks [RRs]) of common
      cancers associated with use of antioxidants, either individually or in
      combination. Subgroup analyses were conducted to determine if duration of use
      modified the association of supplement use with cancer risk. All statistical
      tests were two-sided. RESULTS: During an average 9.4 years of treatment, 624
      women developed incident invasive cancer and 176 women died from cancer. There
      were no statistically significant effects of use of any antioxidant on total
      cancer incidence. Compared with the placebo group, the RRs were 1.11 (95%
      confidence interval [CI] = 0.95 to 1.30) in the vitamin C group, 0.93 (95% CI =
      0.79 to 1.09) in the vitamin E group, and 1.00 (95% CI = 0.85 to 1.17) in the
      beta carotene group. Similarly, no effects of these antioxidants were observed on
      cancer mortality. Compared with the placebo group, the RRs were 1.28 (95% CI =
      0.95 to 1.73) in the vitamin C group, 0.87 (95% CI = 0.65 to 1.17) in the vitamin
      E group, and 0.84 (95% CI = 0.62 to 1.13) in the beta carotene group. Duration
      and combined use of the three antioxidants also had no effect on cancer incidence
      and cancer death. CONCLUSIONS: Supplementation with vitamin C, vitamin E, or beta
      carotene offers no overall benefits in the primary prevention of total cancer
      incidence or cancer mortality.

PMID- 19116390
TI  - Building a knowledge base on genetic variation and cancer risk through field
      synopses.

PMID- 19116391
TI  - Exploring the gender differences in protective factors: implications for
      understanding resiliency.
AB  - Understanding the causes of why individuals desist from or are resilient to
      delinquency and drug use has become a salient social concern. Much research has
      centered on the effects that protective factors possess in fostering resiliency
      but that research has not fully explored how the effects of protective factors
      might vary across gender. Using a sample of 711 individuals from the National
      Longitudinal Survey of Youth, Child-Mother data set, the authors investigate how
      individual protective factors vary across gender on two measures of resiliency
      that document the lack of involvement in serious delinquency and drug use. They
      also examine whether the accumulation of protective factors varies across gender
      in fostering resiliency. The findings suggest that although males and females
      rely on different individual protective factors to foster resiliency, the
      accumulation of protective factors appears to be equally important for males and
      females in promoting resiliency. The authors discuss theoretical and policy
      implications.

PMID- 19116392
TI  - Reintegration and recidivism.

PMID- 19116393
TI  - Assessing ICU transfers at night: a call to reduce mortality and readmission
      risk.

PMID- 19116395
TI  - Unplanned extubation study leaves questions unanswered.

PMID- 19116396
TI  - Successful management of respiratory failure can improve renal function.

PMID- 19116398
TI  - Care and patience needed for accurate measure of gastric residual volumes.

PMID- 19116400
TI  - Transparent film dressing vs pressure dressing after percutaneous transluminal
      coronary angiography.
AB  - BACKGROUND: Pressure dressings have been used as the standard following sheath
      removal after percutaneous transluminal angioplasty in many institutions.
      Patients complain about discomfort while the dressing is in place, pain when the
      dressing is removed after discharge, and skin complications afterward. Many
      patients have experienced skin irritation where tape has been applied. Nurses
      have also described difficulty assessing the sheath insertion site in the groin
      when a pressure dressing is in place. OBJECTIVES: To compare 3 different
      dressings with respect to effect on bleeding, discomfort voiced by patients, and
      ease of groin assessment in patients after percutaneous transluminal coronary
      angiography. METHODS: A total of 100 patients were randomly assigned to 1 of 3
      groups: pressure dressing, transparent film dressing, or adhesive bandage.
      Outcome variables were bleeding, patient discomfort, and nurse-reported ease of
      observation of the groin site. RESULTS: No bleeding occurred in patients with
      transparent film dressings or adhesive bandages. Patients rated these dressings
      significantly higher than they rated the pressure dressing. Because two-thirds of
      the sample had previously undergone percutaneous transluminal coronary
      angiography, they could compare their experience with the new dressing with
      previous experiences with pressure dressings. Nurses rated the ease of assessing
      the groin significantly higher for the transparent film and adhesive bandage
      dressings than for pressure dressings. CONCLUSIONS: As a result of this study, a
      practice change was made hospital-wide: rather than a standard opaque pressure
      dressing, a transparent film dressing is used for all patients after removal of a
      femoral sheath.

PMID- 19116401
TI  - Intensive care units, communication between nurses and physicians, and patients'
      outcomes.
AB  - BACKGROUND: Various factors in hospitals can adversely affect patients' outcomes,
      including faulty communication between nurses and physicians. Whether specific
      communication elements (timeliness, accuracy, openness, understanding) can
      influence adverse outcomes is unknown. OBJECTIVES: To determine the relationships
      between patients' outcomes and (1) nurses' perceptions of elements of
      communication between nurses and physicians and (2) characteristics of the
      practice environment. METHODS: A cross-sectional survey design was used.
      Information on ventilator-associated pneumonia, bloodstream infection associated
      with a central catheter, and pressure ulcers was collected from 25 intensive care
      units in southeastern Michigan. Simultaneously, 462 nurses in those units
      (response rate, 53.3%) were anonymously surveyed. The Conditions for Work
      Effectiveness Questionnaire-II and the Practice Environment Scale of the Nursing
      Work Index were used to measure characteristics of the practice environment. The
      Intensive Care Unit Nurse-Physician Questionnaire was used to measure
      communication between nurses and physicians. Statistical tests included
      correlation and multiple regression. Analyses were conducted at the unit level.
      RESULTS: Unit response rates varied from 6% to 100%. Together, variability in
      understanding communication and capacity utilization were predictive of 27% of
      the variance in ventilator-associated pneumonia. Timeliness of communication was
      inversely related to pressure ulcers (r= -0.38; P=.06), and workplace empowerment
      and scores on the Acute Physiology and Chronic Health Evaluation III were
      positive predictors of ventilator-associated pneumonia (R(2)=0.36; P=.005).
      CONCLUSIONS: Not all elements of communication were related to the selected
      adverse outcomes. The connection between characteristics of the practice
      environment at the unit level and adverse outcomes remains elusive.

PMID- 19116402
TI  - Patients' bath basins as potential sources of infection: a multicenter sampling
      study.
AB  - BACKGROUND: Nosocomial infections are a marked burden on the US health care
      system and are linked to a high number of patient deaths. OBJECTIVE: To identify
      and quantify bacteria in patients' bath basins and evaluate the basins as a
      possible reservoir for bacterial colonization and a risk factor for subsequent
      hospital-acquired infection. METHODS: In a prospective study at 3 acute care
      hospitals, 92 bath basins, including basins from 3 intensive care units, were
      evaluated. Sterile culture sponges were used to obtain samples from the basins.
      The culture sponges were sent to an outside laboratory, and qualitative and
      quantitative microbial tests were conducted and the results reported. RESULTS:
      Some form of bacteria grew in 98% of the samples (90 sponges), either by plating
      or on enrichment (95% confidence interval, 92%-99.7%). The organisms with the
      highest positive rates of growth on enrichment were enterococci (54%), gram
      negative organisms (32%), Staphylococcus aureus (23%), vancomycin-resistant
      enterococci (13%), methicillin-resistant S aureus (8%), Pseudomonas aeruginosa
      (5%), Candida albicans (3%), and Escherichia coli (2%). Mean plate counts, in
      colony-forming units, were 10 187 for gram-negative organisms, 99 for E coli, 30
      for P aeruginosa, 86 for S aureus, 207 for enterococci, and 31 for vancomycin
      resistant enterococci. CONCLUSIONS: Bath basins are a reservoir for bacteria and
      may be a source of transmission of hospital-acquired infections. Increased
      awareness of bath basins as a possible source of transmission of hospital
      acquired infections is needed, particularly for high-risk patients.

PMID- 19116404
TI  - Autonomic nervous system function and depth of sedation in adults receiving
      mechanical ventilation.
AB  - BACKGROUND: The effect of the depth of sedation on the function of the autonomic
      nervous system is not well known. OBJECTIVES: To describe the effect of level of
      sedation on heart rate variability as a marker of the function of the autonomic
      nervous system in patients receiving mechanical ventilation. METHODS: This pilot
      study was part of a larger study in which sedation level was measured
      continuously for up to 24 hours. The sample consisted of 14 patients receiving
      mechanical ventilation. The R-R interval was measured continuously via
      electrocardiography. Sedation level was determined by using the Patient State
      Index and was categorized as deep (<60) or light (=60). Continuous heart rate
      data of 5 to 10 minutes for each sedation level for each patient were analyzed.
      RESULTS: Parasympathetic activity as indicated by root mean square of successive
      difference of the R-R interval, the high-frequency component, and the percentage
      of differences of successive N-N intervals (intervals due to normal sinus
      depolarization) that differed more than 50 milliseconds was significantly lower
      for deep sedation than for light sedation. The markers indicating sympathetic
      activity, including the low-frequency component and the ratio of the low
      frequency component to the high-frequency component, did not differ significantly
      between the 2 levels of sedation. Most patients were receiving benzodiazepines.
      CONCLUSIONS: Deep sedation may be associated with depression of parasympathetic
      function in patients receiving mechanical ventilation. Use of benzodiazepines
      most likely contributed to this finding.

PMID- 19116405
TI  - Enteral feeding and caloric intake in neonates after cardiac surgery.
AB  - BACKGROUND: Adequate enteral nutrition may be difficult to achieve early in
      neonates after cardiac surgery, but it is essential for growth, wound healing,
      and immune function. OBJECTIVE: To assess caloric intake in neonates receiving
      enteral nutrition after surgery. METHODS: A retrospective chart review was
      conducted of daily enteral caloric intake in the cardiac intensive care unit of a
      tertiary children's hospital. Data on the institution of enteral feeding and the
      discontinuation of parenteral nutrition were assessed for full-term neonates who
      had undergone cardiac surgery. RESULTS: Caloric intake was assessed in 100
      patients, 52 with biventricular cardiac defects and 48 with a functional single
      ventricle. The median duration of stay in the cardiac intensive care unit was 13
      days (range, 4-69), and patients received enteral feeding exclusively for a
      median of 5 days (range, 1-43). In total, 705 patient days were evaluated. The
      median caloric intake per day was 93 kcal/kg (range, 43-142). A goal of 100
      kcal/kg was achieved for 48.4% of patient days and 120 kcal/kg for only 19.7% of
      patient days. Median weight change for the period of enteral feeding was -20 g
      (range, -775 to 1485 g). CONCLUSIONS: Enteral feeding alone is often suboptimal
      after neonatal cardiac surgery. New strategies to improve caloric intake may
      enhance postoperative recovery.

PMID- 19116406
TI  - Increasing reliability of APACHE II scores in a medical-surgical intensive care
      unit: a quality improvement study.
AB  - BACKGROUND: Given their clinical, research, and administrative purposes, scores
      on the Acute Physiology and Chronic Health Evaluation (APACHE) II should be
      reliable, whether calculated by health care personnel or a clinical information
      system. OBJECTIVE: To determine reliability of APACHE II scores calculated by a
      clinical information system and by health care personnel before and after a
      multifaceted quality improvement intervention. METHODS: APACHE II scores of 37
      consecutive patients admitted to a closed, 15-bed, university-affiliated
      intensive care unit were collected by a research coordinator, a database clerk,
      and a clinical information system. After a quality improvement intervention
      focused on health care personnel and the clinical information system, the same
      methods were used to collect data on 32 consecutive patients. The research
      coordinator and the clerk did not know each other's scores or the information
      system's score. The data analyst did not know the source of the scores until
      analysis was complete. RESULTS: APACHE II scores obtained by the clerk and the
      research coordinator were highly reliable (intraclass correlation coefficient,
      0.88 before vs 0.80 after intervention; P = .25). No significant changes were
      detected after the intervention; however, compared with scores of the research
      coordinator, the overall reliability of APACHE II scores calculated by the
      clinical information system improved (intraclass correlation coefficient, 0.24
      before intervention vs 0.91 after intervention, P < .001). CONCLUSIONS: After
      completion of a quality improvement intervention, health care personnel and a
      computerized clinical information system calculated sufficiently reliable APACHE
      II scores for clinical, research, and administrative purposes.

PMID- 19116407
TI  - Differences in glucose values obtained from point-of-care glucose meters and
      laboratory analysis in critically ill patients.
AB  - BACKGROUND: Blood for glucose analysis is often obtained interchangeably from
      indwelling catheters and fingersticks. OBJECTIVES: To determine the level of
      agreement between glucose values obtained by laboratory analysis and with a point
      of-care device for blood from 2 different sources: fingerstick and a central
      venous catheter. METHODS: A method-comparison design was used. Point-of-care
      values for blood from fingersticks and catheters were compared with laboratory
      values for blood from catheters in a convenience sample of 67 critically ill
      patients. The effects of hematocrit level and finger edema on differences in
      glucose values between the 2 methods were also evaluated. A t test was used to
      determine differences in glucose values obtained via the 2 methods. Differences
      and limits of agreement were also calculated. RESULTS: Laboratory glucose values
      for blood from a catheter differed significantly from point-of-care values for
      blood from the catheter (t(1,66) = -9.18; P < .001) and from a fingerstick
      (t(1,66) = 6.53; P < .001). Glucose values for the 2 methods differed by 20 mg/dL
      or more for 1 of 6 patients (15%) for catheter samples and for 1 of 5 (21%) for
      fingerstick samples. Point-of-care glucose values for fingerstick and catheter
      samples did not differ (P = .98). Hematocrit level significantly explained the
      difference in glucose values between the 2 methods for both catheter (R(2) =
      0.288; P < .001) and fingerstick (R(2) = 0.280; P = .02) samples. CONCLUSIONS:
      Use of a commonly used point-of-care device when precise glucose values are
      needed may lead to faulty treatment decisions.

PMID- 19116408
TI  - Feeding tube placement in adults: safe verification method for blindly inserted
      tubes.

PMID- 19116409
TI  - What is documentation for?

PMID- 19116410
TI  - Resting parasympathetic tone.

PMID- 19116411
TI  - Community-acquired methicillin-resistant Staphylococcus aureus epidural abscess
      with bacteremia and multiple lung abscesses: case report.
AB  - A systemic infection due to community-acquired methicillin-resistant
      Staphylococcus aureus occurred in a hospital-naive 17-year-old girl with no
      history of soft-tissue infection. Although the initial signs and symptoms were
      indolent, systemic manifestations occurred, including extensive lung parenchymal
      damage and acute respiratory distress syndrome. The patient required long-term
      mechanical ventilation and was given linezolid for 8 weeks. Blood cultures
      eventually became negative for the staphylococci, and the patient was discharged
      to a rehabilitation facility. A probable source of the infection was the
      patient's self-cutting and self-piercing.

PMID- 19116413
TI  - Psychometric properties of teacher SKAMP ratings from a community sample.
AB  - This study examines the basic psychometric properties of the Swanson, Kotkin,
      Agler, M-Flynn, and Pelham Scale (SKAMP), a measure intended to assess functional
      impairment related to attention deficit hyperactivity disorder, in a sample of
      1,205 elementary students. Reliability, factor structure, and convergent,
      discriminant and predictive validity are evaluated. Results provide support for
      two separate but related subscales, Attention and Deportment, and provide
      evidence that the SKAMP predicts school functioning above and beyond symptoms
      alone. Boys, African American children, and children living in poverty are rated
      as having higher impairment scores than girls, Caucasian children, and more
      advantaged peers. Norm-referenced data are provided by gender, race, and parental
      concern level. This study supports the reliability and validity of the SKAMP in a
      large, diverse community sample and broadens its clinical utility.

PMID- 19116414
TI  - Founding, early history, and transformation of the Journal for Lipid Research to
      an American Society of Biochemistry and Molecular Biology journal.
AB  - The Journal of Lipid Research was founded in October, 1959 and has had a long and
      distinguished history. It evolved from an initial concept of a loose-leaf
      methodology handbook to a major journal for the lipid field. Its growth has in
      many ways paralleled the growth and expansion of lipid research. Today, it is
      operated as a journal of the American Society for Biochemistry and Molecular
      Biology at the forefront of biomedical research on lipids.

PMID- 19116412
TI  - Splicing factor SFRS1 recognizes a functionally diverse landscape of RNA
      transcripts.
AB  - Metazoan genes are encrypted with at least two superimposed codes: the genetic
      code to specify the primary structure of proteins and the splicing code to expand
      their proteomic output via alternative splicing. Here, we define the specificity
      of a central regulator of pre-mRNA splicing, the conserved, essential splicing
      factor SFRS1. Cross-linking immunoprecipitation and high-throughput sequencing
      (CLIP-seq) identified 23,632 binding sites for SFRS1 in the transcriptome of
      cultured human embryonic kidney cells. SFRS1 was found to engage many different
      classes of functionally distinct transcripts including mRNA, miRNA, snoRNAs,
      ncRNAs, and conserved intergenic transcripts of unknown function. The majority of
      these diverse transcripts share a purine-rich consensus motif corresponding to
      the canonical SFRS1 binding site. The consensus site was not only enriched in
      exons cross-linked to SFRS1 in vivo, but was also enriched in close proximity to
      splice sites. mRNAs encoding RNA processing factors were significantly
      overrepresented, suggesting that SFRS1 may broadly influence the post
      transcriptional control of gene expression in vivo. Finally, a search for the
      SFRS1 consensus motif within the Human Gene Mutation Database identified 181
      mutations in 82 different genes that disrupt predicted SFRS1 binding sites. This
      comprehensive analysis substantially expands the known roles of human SR proteins
      in the regulation of a diverse array of RNA transcripts.

PMID- 19116415
TI  - A national patient navigator training program.
AB  - Patient Navigation is an intervention aimed at addressing cancer health
      disparities by eliminating barriers to diagnosis, treatment, and services. Three
      major patient navigation (PN) programs (The National Cancer Institute, The
      American Cancer Society &The Center for Medicare and Medicaid Services) are
      underway to address the needs of medically underserved cancer patients. There has
      not been national training with a defined curriculum for patient navigators
      (PNs). Curriculum for training the PNs was created by experts from the three
      programs. The efficacy of training was evaluated using a pre- and posttest. The
      data show that overall the posttest scores improved from the pretest. In
      addition, having a high school education or greater or having more years of work
      experience were significantly related to improvements on the posttest. The first
      successful standardized national training program was attended by 116 PNs
      representing 85 cities with the goal to reduce health disparities for medically
      underserved.

PMID- 19116417
TI  - Listening to youth: reflections on the effect of a youth development program.
AB  - To identify key elements that contribute to the effectiveness of a youth
      development program, interviews were conducted with 35 former Chicago Youth
      Programs (CYP) participants who remained in the program until age 18 years and
      went on to attend college, and 25 participants who left the program (and are
      currently older than age 18). Of the college participants who remained in CYP
      until age 18, 97% reported that the program had helped them by providing
      tutoring, mentoring, and financial support. In comparison, only 56% of the CYP
      dropouts had completed some college, and nearly 50% reported being involved in
      illegal activities. Many of the CYP dropouts were drawn to illegal activities for
      financial reasons or because they felt there was inadequate adolescent
      programming. All reported benefiting from their CYP participation. Incorporating
      financial incentives or specific adolescent programming may lead to longer youth
      program participation and, perhaps, more positive outcomes.

PMID- 19116416
TI  - Adaptation of a lay health advisor model as a recruitment and retention strategy
      in a clinical trial of college student smokers.
AB  - This study describes and provides results from a process evaluation of a lay
      health advisor (LHA) model to enhance participation in a clinical trial of the
      effectiveness of motivational interviewing on smoking cessation in college
      fraternity and sorority members. The implementation of the model had two phases:
      (a) the selection and training of LHAs as liaisons between research staff and
      participants and (b) LHAs' roles in recruitment and retention. Perceptions of the
      LHA model were explored using survey questionnaires. Trial participants (N = 118)
      and LHAs (N = 8) were generally satisfied with the model and identified LHAs as
      helpful to participation. Seventy-four percent of chapter members were screened
      and 73% of participants received three of the four motivational interviewing
      sessions. These results indicate the LHA model was well received and met the
      needs of the research project.

PMID- 19116418
TI  - Using theory and technology to design a practical and generalizable smoking
      reduction intervention.
AB  - The aim of this article is to describe the process of using theory to form
      strategies for a generalizable smoking reduction intervention delivered through
      multiple intervention modalities. This report describes the process of
      integrating theory, data from diverse sources, staff from three different
      organizations, and different intervention modalities into an efficient, large
      scale smoking reduction program featuring automated data from electronic medical
      records, computer-assisted telephone interviews, and tailored newsletters. The
      authors successfully developed a program that was consistently implemented as
      planned for 320 smokers in a managed care organization. The mapping of theory to
      intervention, data transfer and security procedures, and processes and strategies
      used to overcome challenges to intervention implementation should provide lessons
      learned for similar health promotion projects. Few intervention studies discuss
      details of how they translate theory into practice or how they integrate
      different modalities and collaborating institutions, but such integration is
      critical for project success.

PMID- 19116419
TI  - An evaluation of the experiences of rural MSM who accessed an online HIV/AIDS
      health promotion intervention.
AB  - The purpose of this study was to assess rural MSM's satisfaction with an Internet
      delivered HIV/AIDS intervention. Objectives were to evaluate if completion rates
      varied by characteristics, if completion varied by computer issues, if
      satisfaction changed from first to last modules, and if satisfaction was
      associated with module order. Data were collected from 300 rural MSM. Results
      showed few differences between men who completed the intervention and those who
      dropped out. Completion was associated with income, accessing the intervention at
      home, time to load screens, and finding navigation easy. For those completing the
      intervention, interest in and perceived usefulness of the information increased
      from first to the last module. Module order was associated with the knowledge
      module. Interest in the module was greatest if it was encountered last. Results
      indicate that rural MSM are willing to enroll in and complete an Internet
      delivered HIV/AIDS risk reduction intervention.

PMID- 19116420
TI  - A qualitative examination of perceptions of physical activity guidelines and
      preferences for format.
AB  - A descriptive exploratory study was conducted to gain an understanding of public
      perceptions of physical activity guidelines and to discover what formats appeal
      to participants. Canada's Physical Activity Guide (CPAG) was used as an example
      of such guidelines. Data were collected from 22 participants in five focus groups
      (composed of female undergraduate students, female office workers, male office
      workers, participants in a Type II diabetes rehabilitation program, and
      participants in a cardiovascular rehabilitation program). Cross-case qualitative
      analyses were conducted. Six themes emerged under the general categories of
      familiarity and preferences for PA promotional materials. In terms of
      familiarity, participants lacked awareness of CPAG and criticized its format. In
      terms of preferences, participants encouraged the use of stylistically similar
      messaging to those used by commercial advertisers, wanted personal stories,
      Internet-based media, and the use of celebrities' success stories. There was
      little awareness of CPAG and the current format was unappealing.

PMID- 19116421
TI  - Strategies to increase health literacy in the infant feeding series (TIFS): a six
      lesson curriculum for low-income mothers.
AB  - Low literacy can be a serious barrier to educating audiences about important
      health issues. This article explicates strategies used to increase health
      literacy in The Infant Feeding Series, a six-lesson curriculum on infant feeding
      practices. The curriculum was developed by a multidisciplinary team of
      researchers, health educators, and community stakeholders with the primary goal
      of increasing low-income mothers' knowledge and self-efficacy to delay the
      introduction of solid foods into infants' diets. Strategies used to develop the
      low literate accessible materials include (a) incorporation of formative research
      and theory, (b) media components, (c) reading level assessment of materials, (d)
      review of materials by multiple stakeholders, (e) one-on-one home delivery, (f)
      pilot evaluation of lessons, and (g) a workbook incentive designed to integrate
      knowledge and motivate participants to complete the curriculum through scrapbook
      activities. These strategies are discussed as they relate to lesson content and
      curriculum effectiveness.

PMID- 19116422
TI  - Center for Disease Control's Diethylstilbestrol Update: a case for effective
      operationalization of messaging in social marketing practice.
AB  - The Center for Disease Control's (CDC) Diethylstilbestrol (DES) Update, a
      campaign to educate people who may have been exposed to the drug DES, is framed
      on the premises of the social marketing model, namely formative research,
      audience segmentation, product, price, placement, promotion, and campaign
      evaluation. More than that, the campaign takes a critical step in extending the
      social marketing paradigm by highlighting the need to situate the messaging
      process at the heart of any health communication campaign. This article uses
      CDC's DES Update as a case study to illustrate an application of a message
      development tool within social marketing. This tool promotes the
      operationalization of messaging within health campaigns. Ultimately, the goal of
      this project is to extend the social marketing model and provide useful
      theoretical guidance to health campaign practitioners on how to accomplish
      stellar communication within a social marketing campaign.

PMID- 19116423
TI  - Developing a cross-site evaluation tool for diverse health interventions.
AB  - The Prevention Research Center of Michigan provided technical assistance for the
      evaluation of 10 projects funded by the Michigan Department of Community Health's
      (MDCH) Health Disparities Reduction Program. These projects varied considerably
      in focus, methodology, geographical coverage, and populations served. The authors
      developed a cross-site evaluation tool to complement the internal evaluations of
      the projects. The tool contains four sections based on priorities identified by
      MDCH: evidence-based practice, research-based learning/evaluation (including
      process, impact, and outcomes indicators), cultural competence, and
      sustainability. Recognizing the diversity of programmatic efforts and
      organizational evaluation capacity, the authors sought to enable each project to
      create the best evaluation possible given the resources and data available. Each
      section contains a range of components from basic questions to more advanced
      evaluation techniques. The instrument attempts to use the highest quality of
      information available for each project. This evaluation tool can be used by
      programs with diverse goals and methodology.

PMID- 19116424
TI  - Promoting community preparedness: lessons learned from the implementation of a
      chemical disaster tabletop exercise.
AB  - Health educators are frequently called on to facilitate community preparedness
      planning. One planning tool is community-wide tabletop exercises. Tabletop
      exercises can improve the preparedness of public health system agencies to
      address disaster by bringing together individuals representing organizations with
      different roles and perspectives in specific disasters. Thus, they have the
      opportunity to identify each other's roles, capabilities, and limitations and to
      problem-solve about how to address the gaps and overlaps in a low-threat
      collaborative setting. In 2005, the North Carolina Office of Public Health
      Preparedness and Response developed a series of exercises to test the
      preparedness for chemical disasters in a metropolitan region in the southeastern
      United States. A tabletop exercise allowed agency heads to meet in an environment
      promoting inter- and intraagency public-private coordination and cooperation. The
      evaluation results reported here suggest ways in which any tabletop exercise can
      be enhanced through recruitment, planning, and implementation.

PMID- 19116425
TI  - But will I be re-elected? What happens to local level policy makers who support
      clean indoor air laws?
AB  - This research was conducted to determine the impact of voting for clean indoor
      air ordinance on a local-level policy maker's re-election status. Secondary data
      were used to identify local tobacco ordinances in Arizona proposed between 2001
      and 2005, score ordinance content for comprehensiveness, identify policy makers
      who voted and how they voted, and determine if the measure passed or failed.
      Participation in and outcomes of subsequent elections were documented from public
      records. Ninety-two local-level policy makers in 15 local jurisdictions
      considered clean indoor air laws between 2001 and 2005. Policy makers who voted
      for these ordinances were more likely to be re-elected than those who voted
      against them. Structured interviews revealed that policy makers did not believe
      the issue had an impact on re-election results and believed that although the
      issue may have been contentious, it was no longer salient in the community.

PMID- 19116426
TI  - Dissemination of a breast and cervical cancer early detection program through a
      network of community-based organizations.
AB  - ENCORE (plus) , a breast and cervical cancer outreach, education, and screening
      referral program, was implemented by the YWCA of the United States and funded by
      Avon's Breast Cancer Awareness Crusade. ENCORE (plus) was designed to address the
      educational and access needs of low socioeconomic status and minority women who
      experience substantial barriers to breast and cervical cancer screening. This
      article describes the dissemination of ENCORE (plus) to 78 YWCAs in 30 states. It
      illustrates the application of social cognitive theory and diffusion theory to
      increase program adoption, implementation, and maintenance among community
      organizations that have not traditionally provided public health related
      services. The article highlights elements of the program that enhanced its
      adoption and implementation and describes procedures for accelerating the
      diffusion of the program across the country.

PMID- 19116427
TI  - Participatory prevention research model promotes environmental change for
      healthier schools.
AB  - Barriers exist to healthy eating and physical activity for children in the school
      environment. Modifiable school environmental factors have led to the development
      of the Nutrition Friendly Schools and Communities (NFSC) model to prevent the
      development of overweight in school children and adolescents. The design of the
      NFSC environmental intervention is to actively engage the school community to
      prevent overweight in school-aged children. This article presents data measuring
      the environmental changes achieved by the Los Angeles Unified School District
      (LAUSD) elementary schools participating in a 3-year participatory research pilot
      study funded by the Centers for Disease Control and Prevention (CDC). An
      objective of the pilot study is to determine whether any or all of the 15 steps
      developed for the NFSC model could be implemented. Further, researchers want to
      know if any of the study schools could implement the NFSC model as a whole during
      the allotted time of the pilot study.

PMID- 19116429
TI  - "Oh, the places you'll go!": assessing work preferences and personal assets.

PMID- 19116430
TI  - Textbook writing: a form of professional development.
AB  - Health educators have an ethical obligation to participate in professional
      development. Such professional development can take many different forms
      including writing textbooks. This article provides a rationale why textbook
      writing is professional development, why professionals might take on the task of
      writing a textbook, how the process evolves, and how professionals who are not
      quite ready to write a book can prepare to do so in the future.

PMID- 19116431
TI  - Expanding education technology to meet the needs of patients, families, and
      clinicians.
AB  - With the patient length of hospital stay continuously decreasing, health
      educators and nurses are continually challenged to adequately educate patients
      prior to discharge. Health education is recognized as a key component for
      reducing readmission rates by increasing patient compliance, yet health education
      resources must be readily accessible to patients throughout the entire hospital
      experience in order to achieve fulfillment. The Center for Consumer Health
      Information at Cleveland Clinic examined the existing in-hospital delivery
      systems in order to identify a means to reach patients at all access points in
      the health care process. This article demonstrates how a closed circuit
      television system may be utilized to deliver health education content to
      individuals in both in-patient and out-patient settings. The evaluation of
      vendors and identification of internal resources is imperative to the successful
      implementation of an in-patient education system.

PMID- 19116432
TI  - Health behavior insights: the transtheoretical/stages of change model: Carlo C.
      DiClemente, PhD.
AB  - Showcased in this article is an interview with Carlo C. DiClemente, PhD, an
      internationally renowned health behavior researcher and codeveloper of the
      Transtheoretical or Stages of Change Model. In this verbatim interview
      transcript, later edited by the authors and interviewee, Dr. DiClemente, he
      provides practical information and frank commentary on the steps to follow and
      pitfalls to avoid in developing, implementing, evaluating, and disseminating
      efficacious programs for affecting the health and well-being of individuals and
      populations. A concluding section summarizes key lessons learned from the
      professional experiences of Dr. DiClemente and discusses implications for
      advancing health behavior intervention practice and research.

PMID- 19116433
TI  - A key role for floral scent in a wasp-pollination system in Eucomis
      (Hyacinthaceae).
AB  - BACKGROUND AND AIMS: Floral scent may play a key role as a selective attractant
      in plants with specialized pollination systems, particularly in cases where
      floral morphology does not function as a filter of flower visitors. The
      pollination systems of two African Eucomis species (E. autumnalis and E. comosa)
      were investigated and a test was made of the importance of scent and visual cues
      as floral attractants. METHODS AND KEY RESULTS: Visitor observations showed that
      E. autumnalis and E. comosa are visited primarily by pompilid wasps belonging to
      the genus Hemipepsis. These wasps carry considerably more Eucomis pollen and are
      more active on flowers than other visiting insects. Furthermore, experiments
      involving virgin flowers showed that these insects are capable of depositing
      pollen on the stigmas of E. autumnalis, and, in the case of E. comosa, pollen
      deposited during a single visit is sufficient to result in seed set. Experimental
      hand-pollinations showed that both species are genetically self-incompatible and
      thus reliant on pollinators for seed set. Choice experiments conducted in the
      field and laboratory with E. autumnalis demonstrated that pompilid wasps are
      attracted to flowers primarily by scent and not visual cues. Measurement of
      spectral reflectance by flower petals showed that flowers are cryptically
      coloured and are similar to the background vegetation. Analysis of headspace
      scent samples using coupled gas chromatography-mass spectrometry revealed that E.
      autumnalis and E. comosa scents are dominated by aromatic and monoterpene
      compounds. One hundred and four volatile compounds were identified in the floral
      scent of E. autumnalis and 83 in the floral scent of E. comosa, of which 57 were
      common to the scents of both species. CONCLUSIONS: This study showed that E.
      autumnalis and E. comosa are specialized for pollination by pompilid wasps in the
      genus Hemipepsis and achieve specialization through cryptic colouring and the use
      of scent as a selective floral attractant.

PMID- 19116434
TI  - Water immersion: does it enhance recovery from exercise?
AB  - PURPOSE: To assess the effect that postexercise immersion in water has on
      subsequent exercise performance. METHODS: A literary search and review of water
      immersion and performance studies was conducted. RESULTS: Seven articles were
      examined. In 2, significant benefits to performance were observed. Those 2
      articles revealed a small to large effect on jump performance and isometric
      strength. PRACTICAL APPLICATION AND CONCLUSIONS: It is possible that water
      immersion might improve recovery from plyometric or muscle-damaging exercise.
      Such a statement needs to be verified, however, because of the scarcity of
      research on water immersion as a recovery strategy.

PMID- 19116435
TI  - Off-ice performance and draft status of elite ice hockey players.
AB  - PURPOSE: The primary purpose of this study was to determine whether tests
      performed at the National Hockey League (NHL) Combine could distinguish draft
      status (ie, the round selected). A secondary aim was to provide performance
      ranges and percentiles for each of the dependent variables. METHODS: A
      retrospective, cross-sectional study design was used with performance data and
      draft order from 2001, 2002, and 2003 Combine participants. Draft round was
      divided into 5 classifications (rounds 1, 2, 3, 4, and 5 through 9), and
      performances on 12 physical tests served as dependent variables. Three multiple
      analyses of covariance (MANCOVAs) were used to determine the significance of
      performance scores at the NHL Combine on draft selection. Age (years), body mass
      (kg), height (cm), and percentage body fat were treated as covariates. RESULTS:
      Overall, MANCOVA results indicated no significant effect of performance on draft
      selection for 2001, 2002, or 2003. Subsequent univariate tests revealed that no
      single dependent variable was able to distinguish between draft rounds for any of
      the 3 years sampled. CONCLUSIONS: Using draft status as an indicator of ice
      hockey performance, it appears that off-ice tests cannot accurately predict ice
      hockey playing ability in an elite group of athletes. This might stem from
      homogeneity of the Combine participants, a lack of validity of the tests, or
      other factors (eg, on-ice hockey skills, psychological variables, etc) that play
      a role in draft selection.

PMID- 19116436
TI  - The work rate corresponding to ventilatory threshold during steady-state and ramp
      exercise.
AB  - PURPOSE: The work rate (WR) corresponding to ventilatory threshold (VT) is an
      appropriate intensity for regenerative and low-intensity training sessions.
      During incremental ramp exercise, VO(2) increase lags behind WR increase.
      Traditionally, a VO(2) time delay (t(d)) of 45 seconds is used to calculate the
      WR at VT from such tests. Considerable inaccuracies were observed when using this
      constant td. Therefore, this study aimed at reinvestigating the temporal
      relationship between VO(2) and WR at VT. METHODS: 20 subjects (VO(2peak) 49.9 to
      72.6 mL x min-1 x kg-1) performed a ramp test in order to determine VT and a
      subsequent steady-state test during which WR was adjusted to elicit the VO(2)
      corresponding to VT. The difference in WR and heart rate at VT was calculated
      between the ramp and the steady-state test (WR(diff), HR(diff)) as well as the
      time delay corresponding to WR(diff) during ramp exercise. RESULTS: Mean values
      were td = 85 + or - 26 seconds (range 38 to 144), WR(diff) = 45 + or - 12 W
      (range 23 to 67), HR(diff) = 1 + or - 9 beats/min (range -21 to +15). The limits
      of agreement for the difference between WR at VT during ramp and steady-state
      exercise were + or - 24 W. No significant influence on td, WR(diff), or HR(diff)
      from differences in endurance capacity (VO(2peak) and VT; P > .10 for all
      correlations) or ramp increment (P = .26, .49, and .85, respectively) were
      observed. CONCLUSION: The wide ranges of td, WR(diff), and HR(diff) prevent the
      derivation of exact training guidelines from single-ramp tests. It is advisable
      to perform a steady-state test to exactly determine the WR corresponding to VT.

PMID- 19116437
TI  - An analysis of pacing strategies during men's world-record performances in track
      athletics.
AB  - PURPOSE: To analyze pacing strategies employed during men's world-record
      performances for 800-m, 5000-m, and 10,000-m races. METHODS: In the 800-m event,
      lap times were analyzed for 26 world-record performances from 1912 to 1997. In
      the 5000-m and 10,000-m events, times for each kilometer were analyzed for 32
      (1922 to 2004) and 34 (1921 to 2004) world records. RESULTS: The second lap in
      the 800-m event was significantly slower than the first lap (52.0 + or - 1.7 vs
      54.4 + or - 4.9 seconds, P < .00005). In only 2 world records was the second lap
      faster than the first lap. In the 5000-m and 10,000-m events, the first and final
      kilometers were significantly faster than the middle kilometer intervals,
      resulting in an overall even pace with an end spurt at the end. CONCLUSION: The
      optimal pacing strategy during world-record performances differs for the 800-m
      event compared with the 5000-m and 10,000-m events. In the 800-m event, greater
      running speeds are achieved in the first lap, and the ability to increase running
      speed on the second lap is limited. In the 5000-m and 10,000-m events, an end
      spurt occurs because of the maintenance of a reserve during the middle part of
      the race. In all events, pacing strategy is regulated in a complex system that
      balances the demand for optimal performance with the requirement to defend
      homeostasis during exercise.

PMID- 19116438
TI  - High-intensity kayak performance after adaptation to intermittent hypoxia.
AB  - CONTEXT: Live-high train-low altitude training produces worthwhile gains in
      performance for endurance athletes, but the benefits of adaptation to various
      forms of artificial altitude are less clear. PURPOSE: To quantify the effects of
      intermittent hypoxic exposure on kayak performance. METHODS: In a crossover
      design with a 6-week washout, we randomized 10 subelite male sprint kayak
      paddlers to hypoxia or control groups for 3 weeks (5 days/week) of intermittent
      hypoxic exposure using a nitrogen-filtration device. Each day's exposure
      consisted of alternately breathing hypoxic and ambient air for 5 minutes each
      over 1 hour. Performance tests were an incremental step test to estimate peak
      power, maximal oxygen uptake, exercise economy, and lactate threshold; a 500-m
      time trial; and 5 x 100-m sprints. All tests were performed on a wind-braked
      kayak ergometer 7 and 3 days pretreatment and 3 and 10 days posttreatment.
      Hemoglobin concentration was measured at 1 day pretreatment, 5 and 10 days during
      treatment, and 3 days after treatment. RESULTS: Relative to control, at 3 days
      posttreatment the hypoxia group showed the following increases: peak power 6.8%
      (90% confidence limits, + or - 5.2%), mean repeat sprint power 8.3% (+ or -
      6.7%), and hemoglobin concentration 3.6% (+ or - 3.2%). Changes in lactate
      threshold, mean 500-m power, maximal oxygen uptake, and exercise economy were
      unclear. Large effects for peak power and mean sprint speed were still present 10
      days posthypoxia. CONCLUSION: These effects of intermittent hypoxic exposure
      should enhance performance in kayak racing. The effects might be mediated via
      changes in oxygen transport.

PMID- 19116439
TI  - Acute explosive-force movements enhance bench-press performance in athletic men.
AB  - PURPOSE: The purpose of this investigation was to determine whether the
      performance of explosive-force movements before bench-press exercise would
      improve 1-repetition-maximum (1RM) strength. METHODS: Twelve male college
      athletes participated in 3 testing sessions separated by at least 5 days of rest.
      During each testing session, the 1RM was assessed on the bench-press exercise.
      After a general warm-up, subjects performed a specific warm-up that consisted of
      submaximal sets with increasing loads on the bench-press exercise before
      attempting a 1RM lift. During the first testing trial, subjects performed a
      series of 1RM attempts with increasing loads until their 1RM was determined.
      During the second and third testing trials, subjects performed in a
      counterbalanced randomized order either 2 plyometric push-ups or 2 medicine-ball
      (3 to 5 kg) chest passes 30 seconds before each 1RM attempt. RESULTS: Analysis of
      the data revealed that 1RM bench-press strength was significantly greater after
      plyometric push-ups (P = .004) or chest passes (P = .025) in comparison with the
      first trial (123.8 + or - 23.5 kg and 124.0 + or - 24.1 kg vs 120.9 + or - 23.2
      kg, respectively). CONCLUSIONS: These data suggest that an acute bout of low
      volume, explosive-force upper body movements performed 30 seconds before a 1RM
      attempt might enhance bench-press performance in athletic men.

PMID- 19116440
TI  - Relationship between running velocity of 2 distances and various lactate
      parameters.
AB  - PURPOSE: The purpose of this study was to determine the relationship between
      various lactate-threshold (LT) definitions and the average running velocity
      during a 10-km and a 21.1-km time trial (TT). METHODS: Thirteen well-trained
      runners completed an incremental maximal exercise test, a 10-km TT, and a 21.1-km
      TT on a motorized treadmill. Blood samples were collected through a venous
      catheter placed in an antecubital vein. Pearson's correlation coefficients were
      used to determine the relationship between the running velocity at the different
      LT definitions and the average running velocity during each TT. A dependent t
      test was used to determine statistical differences for the mean lactate response
      between the 2 running distances. RESULTS: The LT(Dmax), the point on the
      regression curve that yielded the maximal perpendicular distance to the straight
      line formed by the 2 endpoints, was the LT definition with the highest
      correlation for both 10-km (r = .844) and 21.1-km TTs (r = .783). The velocity at
      the LT(Dmax) was not, however, the velocity closest to the performance velocity
      for either distance. The mean running velocity at each LT was significantly
      different and tended to overestimate the mean TT performance velocities. The mean
      lactate concentration during the 10-km TT (3.52 + or - 1.58 mmol) was
      significantly higher than during the 21.1-km TT (1.86 + or - 0.90 mmol).
      CONCLUSION: These results indicate that a single LT point cannot be reliably
      associated with different running distances. Furthermore, these data suggest that
      a different methodology for estimating the LT that considers individual responses
      might be required for different running distances.

PMID- 19116441
TI  - Training for performance: insights from molecular biology.
AB  - In this commentary the authors discuss the molecular basis of the training
      adaptation and review the role of several key signaling proteins important in the
      adaptation to endurance and resistance training.

PMID- 19116442
TI  - The flywheel leg-curl machine: offering eccentric overload for hamstring
      development.

PMID- 19116443
TI  - Plyometric training in Gaelic games: a case study on a county-level hurler.
AB  - A 10-week plyometrics-based intervention was carried out with a county-level
      hurler during preseason preparation. The intervention resulted in a number of
      physiological changes specific to hurling performance. Most notably, it enabled
      the athlete to complete repeated sprints with less decrement in performance
      compared with baseline scores.

PMID- 19116444
TI  - Polarization of protective immunity induced by replication-incompetent adenovirus
      expressing glycoproteins of pseudorabies virus.
AB  - Replication-incompetent adenoviruses expressing three major glycoproteins (gB,
      gC, and gD) of pseudorabies virus (PrV) were constructed and used to examine the
      ability of these glycoproteins to induce protective immunity against a lethal
      challenge. Among three constructs, recombinant adenovirus expressing gB (rAd-gB)
      was found to induce the most potent immunity biased to Th1-type, as determined by
      the IgG isotype ratio and the profile of the Th1/Th2 cytokine production.
      Conversely, the gC-expressing adenovirus (rAd-gC) revealed Th2-type immunity and
      the gD-expressing adenovirus (rAd-gD) induced lower levels of IFN-? and IL-4
      production than other constructs, except IL-2 production. Mucosal delivery of rAd
      gB induced mucosal IgA and serum IgG responses and biased toward Th2-type immune
      responses. However, these effects were not observed in response to systemic
      delivery of rAd-gB. In addition, rAd-gB appeared to induce effective protective
      immunity against a virulent viral infection, regardless of whether it was
      administered via the muscular or systemic route. These results suggest that
      administration of replication-incompetent adenoviruses can induce different types
      of immunity depending on the expressed antigen and that recombinant adenoviruses
      expressing gB induced the most potent Th1-biased humoral and cellular immunity
      and provided effective protection against PrV infection.

PMID- 19116445
TI  - Protein kinase Cmu plays an essential role in hypertonicity-induced heat shock
      protein 70 expression.
AB  - Heat shock protein 70 (HSP70), which evidences important functions as a molecular
      chaperone and anti-apoptotic molecule, is substantially induced in cells exposed
      to a variety of stresses, including hypertonic stress, heavy metals, heat shock,
      and oxidative stress, and prevents cellular damage under these conditions.
      However, the molecular mechanism underlying the induction of HSP70 in response to
      hypertonicity has been characterized to a far lesser extent. In this study, we
      have investigated the cellular signaling pathway of HSP70 induction under
      hypertonic conditions. Initially, we applied a variety of kinase inhibitors to
      NIH3T3 cells that had been exposed to hypertonicity. The induction of HSP70 was
      suppressed specifically by treatment with protein kinase C (PKC) inhibitors
      (Go6976 and GF109203X). As hypertonicity dramatically increased the
      phosphorylation of PKCmu, we then evaluated the role of PKCmu in hypertonicity
      induced HSP70 expression and cell viability. The depletion of PKCmu with siRNA or
      the inhibition of PKCmu activity with inhibitors resulted in a reduction in HSP70
      induction and cell viability. Tonicity-responsive enhancer binding protein
      (TonEBP), a transcription factor for hypertonicity-induced HSP70 expression, was
      translocated rapidly into the nucleus and was modified gradually in the nucleus
      under hypertonic conditions. When we administered treatment with PKC inhibitors,
      the mobility shift of TonEBP was affected in the nucleus. However, PKCmu
      evidenced no subcellular co-localization with TonEBP during hypertonic exposure.
      From our results, we have concluded that PKCmu performs a critical function in
      hypertonicity-induced HSP70 induction, and finally cellular protection, via the
      indirect regulation of TonEBP modification.

PMID- 19116446
TI  - Lysophosphatidic acid receptor 2 and Gi/Src pathway mediate cell motility through
      cyclooxygenase 2 expression in CAOV-3 ovarian cancer cells.
AB  - Lysophosphatidic acid (LPA) is a bioactive phospholipids and involves in various
      cellular events, including tumor cell migration. In the present study, we
      investigated LPA receptor and its transactivation to EGFR for cyclooxygenase-2
      (COX-2) expression and cell migration in CAOV-3 ovarian cancer cells. LPA induced
      COX-2 expression in a dose-dependent manner, and pretreatment of the cells with
      pharmacological inhibitors of Gi (pertussis toxin), Src (PP2), EGF receptor
      (EGFR) (AG1478), ERK (PD98059) significantly inhibited LPA- induced COX-2
      expression. Consistent to these results, transfection of the cells with selective
      Src siRNA attenuated COX-2 expression by LPA. LPA stimulated CAOV-3 cell
      migration that was abrogated by pharmacological inhibitors and antibody of EP2.
      Higher expression of LPA2 mRNA was observed in CAOV-3 cells, and transfection of
      the cells with a selective LPA2 siRNA significantly inhibited LPA-induced
      activation of EGFR and ERK, as well as COX-2 expression. Importantly, LPA2 siRNA
      also blocked LPA-induced ovarian cancer cell migration. Collectively, our results
      clearly show the significance of LPA2 and Gi/Src pathway for LPA-induced COX-2
      expression and cell migration that could be a promising drug target for ovarian
      cancer cell metastasis.

PMID- 19116447
TI  - Liposomal honokiol, a potent anti-angiogenesis agent, in combination with
      radiotherapy produces a synergistic antitumor efficacy without increasing
      toxicity.
AB  - Honokiol is an active compound purified from magnolia that has been shown to
      induce cell differentiation, apoptosis, and anti-angiogenesis effects, as well as
      an enhancement in tumor growth delay in combination with chemotherapeutic agents
      in several mouse xenograft models. Our goal was to investigate the
      radiosensitization effect of honokiol on lung carcinoma. The radiosensitization
      effect of liposomal honokiol in Lewis lung carcinoma cells (LL/2) was analyzed
      using an in vitro clonogenic survival assay. For an in vivo study, Lewis lung
      carcinoma-bearing C57BL/6 mice were treated with either liposomal honokiol at 25
      mg/kg or 5 Gy of single tumor radiation, or a combination of both over 12 days of
      treatment. The tumor growth delay and the survival time were evaluated. In
      addition, histological analysis of tumor sections was performed to examine
      changes by detecting the microvessel density and apoptosis in tumor tissues. In
      the clonogenic survival assay, LL/2 cells treated with IC(50) Lipo-HNK for 24 h
      showed a radiation enhancement ratio of 1.9. After 12 days of combination
      treatment, the tumor volume decreased 78% and produced an anti-tumor activity 1.3
      fold greater than a predicted additive effect of honokiol and radiation alone.
      This combination treatment also caused an 8.7 day delay in tumor growth. The cell
      cycle distribution and histological analysis demonstrated that liposomal honokiol
      has an anti-tumor effect via inducing apoptosis and inhibiting angiogenesis.
      Liposomal honokiol can enhance tumor cell radiosensitivity in vitro and in vivo,
      indicating that radiotherapy combined with liposomal honokiol can lead to greater
      anti-tumor efficacy.

PMID- 19116448
TI  - Inhibition of LPS-induced cyclooxygenase 2 and nitric oxide production by
      transduced PEP-1-PTEN fusion protein in Raw 264.7 macrophage cells.
AB  - Phosphatase and tensin homologue deleted on chromosome 10 (PTEN) is a tumor
      suppressor. Although it is well known to have various physiological roles in
      cancer, its inhibitory effect on inflammation remains poorly understood. In the
      present study, a human PTEN gene was fused with PEP-1 peptide in a bacterial
      expression vector to produce a genetic in-frame PEP-1-PTEN fusion protein. The
      expressed and purified PEP-1-PTEN fusion protein were transduced efficiently into
      macrophage Raw 264.7 cells in a time- and dose- dependent manner when added
      exogenously in culture media. Once inside the cells, the transduced PEP-1-PTEN
      protein was stable for 24 h. Transduced PEP-1-PTEN fusion protein inhibited the
      LPS-induced cyclooxygenase 2 (COX-2) and iNOS expression levels in a dose
      dependent manner. Furthermore, transduced PEP-1-PTEN fusion protein inhibited the
      activation of NF-kappaB induced by LPS. These results suggest that the PEP-1-PTEN
      fusion protein can be used in protein therapy for inflammatory disorders.

PMID- 19116449
TI  - Transcriptional induction of DLC-1 gene through Sp1 sites by histone deacetylase
      inhibitors in gastric cancer cells.
AB  - We previously reported that trichostatin A (TSA), a histone deacetylase (HDAC)
      inhibitor, induced DLC-1 mRNA expression and accumulated acetylated histones H3
      and H4 associated with the DLC-1 promoter in DLC-1 non-expressing gastric cancer
      cells. In this study, we demonstrated the molecular mechanisms by which TSA
      induced the DLC-1 gene expression. Treatment of the gastric cancer cells with TSA
      activates the DLC-1 promoter activity through Sp1 sites located at -219 and -174
      relative to the transcription start site. Electrophoretic mobility-shift assay
      (EMSA) revealed that Sp1 and Sp3 specifically interact with these Sp1 sites and
      showed that TSA did not change their binding activities. The ectopic expression
      of Sp1, but not Sp3, enhances the DLC-1 promoter responsiveness by TSA.
      Furthermore, the TSA-induced DLC-1 promoter activity was increased by p300
      expression and reduced by knockdown of p300. These results demonstrated the
      requirement of specific Sp1 sites and dependence of Sp1 and p300 for TSA-mediated
      activation of DLC-1 promoter.

PMID- 19116450
TI  - Curcuminoid-phospholipid complex induces apoptosis in mammary epithelial cells by
      STAT-3 signaling.
AB  - Curcumin (from the rhizome of Curcuma longa) is well documented for its medicinal
      properties in Indian and Chinese systems of medicine where it is widely used for
      the treatment of several diseases. Epidemiological observations are suggestive
      that curcumin consumption may reduce the risk of some form of cancers and provide
      other protective biological effects in humans. These biological properties have
      been attributed to curcuminoids that have been widely studied for their anti
      inflammatory, anti-angiogenic, antioxidant, wound healing and anti-cancer
      effects. In this study we have investigated on the effect of a curcumin
      phospholipid complex on mammary epithelial cell viability. HC11 and BME-UV cell
      lines, validated models to study biology of normal, not tumoral, mammary
      epithelial cells, were used to analyse these effects. We report that curcumin
      acts on STAT-3 signal pathway to reduce cell viability and increase apoptosis
      evaluated by the the amount of activated caspase 3. Further it reduces MAPK and
      AKT activations. JSI-124, a STAT-3 inhibitor (100 nM) was able to block the
      negative effect of curcumin on cell viability and caspase 3 activation. Finally
      the negative effect of cucumin on cell viability has been impaired in STAT-3i
      HC11, where STAT-3 protein was greatly reduced by shRNA-interference. These
      results indicate that curcumin presents a potential adverse effect to normal
      mammary epithelial cells and that it has a specific effect on signal trasduction
      in mammary epithelium.

PMID- 19116452
TI  - Increased in vivo immunological potency of HB-110, a novel therapeutic HBV DNA
      vaccine, by electroporation.
AB  - Pulse-induced permeabilization of cellular membranes, generally referred to as
      electroporation (EP), has been used for years as a tool to increase macromolecule
      uptake in tissues, including nucleic acids, for gene therapeutic applications,
      and this technique has been shown to result in improved immunogenicity. In this
      study, we assessed the utility of EP as a tool to improve the efficacy of HB-110,
      a novel therapeutic DNA vaccine against chronic hepatitis B, now in phase 1 of
      clinical study in South Korea. The potency of HB-110 in mice was shown to be
      improved by EP. The rapid onset of antigen expression and higher magnitude of
      humoral and cellular responses in electric pulse-treated mice revealed that EP
      may enable a substantial reduction in the dosage of DNA vaccine required to
      elicit a response similar in magnitude to that achievable via conventional
      administration. This study also showed that EP-based vaccination at 4-week
      intervals elicited a cellular immune response which was about two-fold higher
      than the response elicited by conventional vaccination at 2-week intervals. These
      results may provide a rationale to reduce the clinical dose and increase the
      interval between the doses in the multidose vaccination schedule. Electric
      pulsing also elicited a more balanced immune response against four antigens
      expressed by HB-110: S, preS, Core, and Pol.

PMID- 19116451
TI  - CD36 signaling inhibits the translation of heat shock protein 70 induced by
      oxidized low density lipoprotein through activation of peroxisome proliferators
      activated receptor gamma.
AB  - Oxidized LDL (OxLDL), a causal factor in atherosclerosis, induces the expression
      of heat shock proteins (Hsp) in a variety of cells. In this study, we
      investigated the role of CD36, an OxLDL receptor, and peroxisome proliferator
      activated receptor gamma (PPARgamma) in OxLDL-induced Hsp70 expression.
      Overexpression of dominant-negative forms of CD36 or knockdown of CD36 by siRNA
      transfection increased OxLDL-induced Hsp70 protein expression in human monocytic
      U937 cells, suggesting that CD36 signaling inhibits Hsp70 expression. Similar
      results were obtained by the inhibition of PPARgamma activity or knockdown of
      PPARgamma expression. In contrast, overexpression of CD36, which is induced by
      treatment of MCF-7 cells with troglitazone, decreased Hsp70 protein expression
      induced by OxLDL. Interestingly, activation of PPARgamma through a synthetic
      ligand, ciglitazone or troglitazone, decreased the expression levels of Hsp70
      protein in OxLDL-treated U937 cells. However, major changes in Hsp70 mRNA levels
      were not observed. Cycloheximide studies demonstrate that troglitazone attenuates
      Hsp70 translation but not Hsp70 protein stability. PPARgamma siRNA transfection
      reversed the inhibitory effects of troglitazone on Hsp70 translation. These
      results suggest that CD36 signaling may inhibit stress- induced gene expression
      by suppressing translation via activation of PPARgamma in monocytes. These
      findings reveal a new molecular basis for the anti-inflammatory effects of
      PPARgamma.

PMID- 19116453
TI  - Glycoproteomic analysis of plasma from patients with atopic dermatitis: CD5L and
      ApoE as potential biomarkers.
AB  - Atopic dermatitis (AD) is an inflammatory skin disorder that is both
      uncomfortable and distressing to patients, and its prevalence has been steadily
      increasing. It is obvious that the identification of efficient markers of AD in
      plasma would offer the possibility of effective diagnosis, prevention, and
      treatment strategies. In this study, a proteomic approach was used to analyze
      plasma glycoproteins from both children with AD and healthy child donors. Several
      protein spots showing significant quantitative changes in the AD patients were
      identified. Through sequential studies, it was confirmed that CD5L and ApoE were
      significantly up-regulated or down-regulated, respectively, in the plasma from AD
      patients compared with that from healthy donors. In addition, we suggest that the
      up-regulated CD5L in AD patients causes eosinophilia by inhibiting apoptosis or
      promoting the proliferation of eosinophils either in combination with or without
      IL-5. The glycoproteomic data in this study provides clues to understanding the
      mechanism of atopic alterations in plasma and suggests AD-related proteins can be
      used as candidate markers for AD.

PMID- 19116454
TI  - Ginsenoside Rb1 attenuates intestinal ischemia-reperfusion- induced liver injury
      by inhibiting NF-kappaB activation.
AB  - Intestinal ischemia-reperfusion (I/R) is an important event in the pathogenesis
      of multiple organ dysfunction syndrome (MODS). The aim of this study is to
      determine the effects of ginsenoside Rb1 on liver injury induced by intestinal
      I/R in rats. Adult male Wistar rats were randomly divided into four groups: (1) a
      control, sham-operated group (sham group); (2) an intestinal I/R group subjected
      to 1 h intestinal ischemia and 2 h reperfusion (I/R group); (3) a group treated
      with 20 mg/kg ginsenoside Rb1 before reperfusion (Rb1-20 group); and (4) a group
      treated with 40 mg/kg ginsenoside Rb1 before reperfusion (Rb1-40 group). Liver
      and intestinal histology was observed. Aspartate aminotransferase (AST), alanine
      aminotransferase (ALT) level in serum and malondialdehyde (MDA) level in
      intestinal tissues were measured. Myeloperoxidase (MPO), TNF-alpha, MDA level and
      immunohistochemical expression of NF-kgr;B and intracellular adhesion molecule-1
      (ICAM-1) in liver tissues was assayed. In addition, a western blot analysis of
      liver NF-kappaB expression was performed. Results indicated intestinal I/R
      induced intestinal and liver injury, which was characterized by increase of AST
      and ALT in serum, MDA level in intestine, MPO, TNF-alpha and MDA level and ICAM-1
      and NF-kappaB expression in the liver tissues. Ginsenoside Rb1 (20, 40 mg/kg)
      ameliorated liver injury, decreased MPO, TNF-alpha and MDA level, NF-kappaB and
      ICAM-1 expression in liver tissues. In conclusion, ginsenoside Rb1 ablated liver
      injury induced by intestinal I/R by inhibiting NF-kappaB activation.

PMID- 19116455
TI  - Transcription of the protein kinase C-delta gene is activated by JNK through c
      Jun and ATF2 in response to the anticancer agent doxorubicin.
AB  - Expression of protein kinase C-delta (PKCdelta) is up-regulated by apoptosis
      inducing stimuli. However, very little is known about the signaling pathways that
      control PKCdelta gene transcription. In the present study, we demonstrate that
      JNK stimulates PKCdelta gene expression via c-Jun and ATF2 in response to the
      anticancer agent doxorubicin (DXR) in mouse lymphocytic leukemia L1210 cells.
      Luciferase reporter assays showed that DXR-induced activation of the PKCdelta
      promoter was enhanced by ectopic expression of JNK1, c-Jun, or ATF2, whereas it
      was strongly reduced by expression of dominant negative JNK1 or by treatment with
      the JNK inhibitor SP600125. Furthermore, point mutations in the core sequence of
      the c-Jun/ATF2 binding site suppressed DXR-induced activation of the PKCdelta
      promoter. Our results suggest an additional role for a JNK signaling cascade in
      DXR-induced PKCdelta gene expression.

PMID- 19116456
TI  - Identification of potential lung cancer biomarkers using an in vitro
      carcinogenesis model.
AB  - Lung cancer is one of the deadliest and commonly diagnosed neoplasms. Early
      diagnosis of this disease is critical for improving clinical outcome and
      prognosis. Because the early stages of lung cancer often produce no symptoms, it
      is necessary to identify biomarkers for early detection, prognostic evaluation,
      and recurrence monitoring of the cancer. To identify potential lung cancer
      biomarkers, we analyzed the differential protein secretion from transformed
      bronchial epithelial cells (1198 and 1170-I) as compared to immortalized normal
      bronchial epithelial cells (BEAS-2B) and non-transformed cells (1799) all of
      which are derived from BEAS-2B and represent multistage bronchial epithelial
      carcinogenesis. The proteins recovered from the conditioned media of the cells
      were separated on two-dimensional gels. There was little difference between the
      secretome of the BEAS-2B and 1799 cells, whereas the patterns between the
      transformed 1198 and 1170-I cells and non-transformed 1799 cells were
      significantly different. Using mass spectrometry and database search, we
      identified 20 proteins including protein gene product 9.5 (PGP9.5),
      translationally controlled tumor protein (TCTP), tissue inhibitors of
      metalloproteinases-2 (TIMP-2), and triosephosphate isomerase (TPI), that were
      either increased or decreased simultaneously in conditioned media of both 1198
      and 1170-I cells. Furthermore, levels of PGP9.5, TCTP, TIMP-2, and TPI were
      significantly increased not only in the conditioned media of both transformed
      cell lines when compared to those of BEAS-2B and 1799 cells, but also in plasmas
      and tissues from lung cancer patients when compared to those in normal controls.
      We suggest the PGP9.5, TCTP, TIMP-2, and TPI as promising candidates for lung
      cancer serum biomarkers.

PMID- 19116457
TI  - Ectopic expression of cyclooxygenase-2-induced dedifferentiation in articular
      chondrocytes.
AB  - Cyclooxygenase-2 (COX-2) is known to modulate bone metabolism, including bone
      formation and resorption. Because cartilage serves as a template for endochondral
      bone formation and because cartilage development is initiated by the
      differentiation of mesenchymal cells into chondrocytes (Ahrens et al., 1977;
      Sandell and Adler, 1999; Solursh, 1989), it is of interest to know whether COX-2
      expression affect chondrocyte differentiation. Therefore, we investigated the
      effects of COX-2 protein on differentiation in rabbit articular chondrocyte and
      chick limb bud mesenchymal cells. Overexpression of COX-2 protein was induced by
      the COX-2 cDNA transfection. Ectopic expression of COX-2 was sufficient to causes
      dedifferentiation in articular chondrocytes as determined by the expression of
      type II collagen via Alcian blue staining and Western blot. Also, COX-2
      overexpression caused suppression of SOX-9 expression, a major transcription
      factor that regulates type II collagen expression, as indicated by the Western
      blot and RT-PCR. We further examined ectopic expression of COX-2 in chondrifying
      mesenchymal cells. As expected, COX-2 cDNA transfection blocked cartilage nodule
      formation as determined by Alcian blue staining. Our results collectively suggest
      that COX-2 overexpression causes dedifferentiation in articular chondrocytes and
      inhibits chondrogenic differentiation of mesenchymal cells.

PMID- 19116461
TI  - A for-profit medical school.

PMID- 19116462
TI  - Underrepresented minorities and the health professions pipeline.

PMID- 19116464
TI  - Burnout in medical school deans.

PMID- 19116466
TI  - Underrepresented minorities and the health professions pipeline.

PMID- 19116468
TI  - Impact of increasing class size.

PMID- 19116469
TI  - Commentary: the right time to rethink part-time careers.
AB  - The demand for part-time academic positions is bound to increase because of the
      changing demographics of medicine and the needs of both women and men faculty.
      One of the main benefits of working part-time is the freedom to shape a career
      that is tailored to one's individualized life needs. Studies indicate that part
      time faculty may enhance quality of care, patient satisfaction, resource
      utilization, and productivity. Division chiefs and department chairs who have
      flexible hiring policies to meet the needs of part-time faculty are likely to be
      more successful in recruitment and retention. The authors describe some of the
      benefits and drawbacks of part-time work, and they offer advice for faculty
      members seeking part-time careers and for leaders seeking to employ them.

PMID- 19116470
TI  - Commentary: surviving terrorist cells.
AB  - The use of violent imagery, war metaphors, and the "survivor" persona in relation
      to cancer research and treatment are examined, as are consumer-driven approaches
      to "working toward a cure." The authors ask, what are the cultural and
      environmental trade-offs of these types of rhetoric? The positions of good guys
      (survivors, researchers, consumers) versus the enemy (cancer) are critically
      evaluated. Of especial note is a recent print advertisement that, despite its
      arresting visual presence, delivers an exceedingly vague message. The authors
      conclude that the practice of medicine plays a pivotal role in these cultural
      determinations and that caricatured attributions of cellular violence ultimately
      divert critical attention from sustained scrutiny of the institutional, social,
      economic, and political processes that in fact may contribute to the forces that
      bear on causing cancer.

PMID- 19116471
TI  - Sangeet kaar/musician: artist's statement.

PMID- 19116472
TI  - A simple model to optimize resource allocations when expanding the faculty
      research base: a case study.
AB  - Construction of new biomedical research facilities has outpaced the funding
      sources for faculty to occupy those facilities. This puts a premium on the
      efficient allocation of central resources for faculty recruitment. The author
      developed a mathematical model to determine the optimal structure (dollars,
      space) for allocating resource packages when recruiting new faculty, based on
      expected financial returns from those faculty. Surprisingly, the optimal strategy
      was to allocate homogeneous recruitment packages, independent of the recruited
      faculty member's rank or the individual's expected revenue generation.
      Optimization results were used to allocate recruitment packages to new department
      head and center directors in the University of Arizona College of Medicine during
      the last four years (2005-2008). At any institution that uses this model,
      appropriate distribution of facilities and administrative revenues at the
      institution is needed to equitably balance the costs and benefits associated with
      faculty expansion.

PMID- 19116473
TI  - The economics of new faculty hires in basic science.
AB  - PURPOSE: To compare the streams of expenses and revenues associated with
      investment in a cohort of basic science investigators at the University of
      Rochester School of Medicine & Dentistry for seven years. METHOD: The authors
      evaluated a medical school's financial investment in 25 basic science faculty who
      were hired between 1999 and 2004 to expand basic science research. The authors
      compared direct and indirect costs with the extramural grant support generated by
      these investigators through 2006. To facilitate a comparison of investments made
      and grants generated, the authors calculated present value (in 2006 dollars) of
      revenues and expenses using the school's approximate cost of capital. RESULTS: Of
      the 25 faculty members hired, 24 (96%) remained at the school through 2006. From
      1999 to 2006, the school invested a total of $69.0 million ($33.1 million in
      start-up costs and $35.9 million in indirect costs) to support the faculty
      members. Through 2006, these faculty members generated $99.7 million in
      extramural grant revenue ($70.7 million in direct grant revenue and $29.1 million
      in indirect grant revenue). Whereas the faculty generated $1.45 in total grant
      revenue per dollar invested, start-up expenses and incomplete recovery of
      indirect costs required the school to add 40 cents to every grant dollar
      generated to achieve financial equilibrium. CONCLUSIONS: Investments in basic
      science research, even when successful, may require significant financial
      subsidies from academic health centers.

PMID- 19116474
TI  - Some hidden costs of faculty turnover in clinical departments in one academic
      medical center.
AB  - PURPOSE: To calculate the costs of clinical faculty turnover in clinical
      departments at The University of Arizona College of Medicine, including some
      aspects of lost clinical income. METHOD: Turnover was defined as the number of
      faculty in each department who left in any given year, divided by the total
      number of faculty with appointments in the department during the same year.
      Turnover rates for generalists, surgeons, and nonsurgical clinical faculty by
      rank were computed from 1999 through 2004 for all clinical departments at the
      University of Arizona College of Medicine. Associated recruitment costs, hiring
      costs, and selected lost clinical income costs-the net clinical practice income
      lost until the faculty member was replaced-were computed for the 17 clinical
      faculty members who left the departments of medicine and surgery during 2004.
      RESULTS: Turnover rates in the two clinical departments ranged from 4.9% to 8.3%
      per year for FY2000-FY2004. Turnover was highest among assistant professors and
      did not differ by gender. The recruitment, hiring, and lost clinical income cost
      of replacing a generalist was $115,554; for replacing a subspecialist, the cost
      was $286,503; and for a surgical subspecialist, the cost was $587,125. The
      average annual cost of turnover for the departments of medicine and surgery
      exceeded $400,000. CONCLUSIONS: Estimates of the financial impact of clinical
      faculty turnover need to include the costs of lost clinical income. The magnitude
      of these costs, although not inclusive of all the financial and nonfinancial
      costs from clinical faculty turnover at an academic medical center, warrants
      additional efforts to foster faculty success and retention.

PMID- 19116475
TI  - Retention of junior faculty in academic medicine at the University of California,
      San Diego.
AB  - PURPOSE: To measure overall retention of junior faculty and evaluate the effects
      of a junior faculty development program on the retention of junior faculty at one
      institution. METHOD: Quantitative survival analysis techniques were used to
      characterize retention of all new assistant professors hired at the University of
      California, San Diego (UCSD) School of Medicine for 18 years between July 1988
      and December 2005, and the influence on retention of a junior faculty development
      program established in 1998. Data available included initial hire date, gender,
      ethnicity, participation in the faculty development program, and date of
      separation from UCSD. Actuarial Kaplan-Meier survival and Cox proportional hazard
      analyses were used to characterize retention and the influence of covariates up
      to the end of the probationary period, eight years after initial hire date.
      RESULTS: For the 839 new assistant professors, participation in the faculty
      development program and being hired after July 1997 had significant effects on
      retention. After adjusting for hire date, gender, and ethnicity, faculty
      participating in the faculty development program were 67% more likely to remain
      at UCSD at the end of their probationary period compared with nonparticipating
      faculty. CONCLUSIONS: Faculty development programs for junior faculty in academic
      medicine can have positive effects on faculty retention and may facilitate
      success in academic medicine.

PMID- 19116476
TI  - How important is money as a reward for teaching?
AB  - PURPOSE: To examine the effect of increases in payment for teaching on retention
      of primary care faculty, and to compare those faculty members' needs and rewards
      for teaching with objective data on retention. METHOD: In 2006-2007, the authors
      compared retention rates of primary care clerkship preceptors at Harvard Medical
      School (1997-2006) when their stipends were raised from $600 to $900 (in 2003)
      and to $2,500 (in 2004), and when faculty received payment directly versus
      indirectly. A survey was sent to all 404 present and past living preceptors, who
      were asked to rank-order six factors in terms of (1) how much they needed each to
      continue teaching, and (2) each factor's contribution to their satisfaction with
      teaching. RESULTS: Retention rates varied from a high of 91% in 2006 to a low of
      69% in 2000. Faculty were 2.66 times more likely (P < .0001) to return to teach
      in the highest pay period than the lowest, and faculty receiving direct payment
      were more likely to continue teaching than those receiving it indirectly. Only 8%
      of the 170 responding faculty ranked receiving the stipend as the most important
      factor in their continuing to teach; no one ranked it first as a source of
      satisfaction. However, 73% ranked having a good student first as a factor in
      continuing to teach; 82% ranked it first as a source of satisfaction. CONCLUSION:
      Raising stipends was associated with increased retention, although faculty ranked
      stipend low in terms of what motivates them to continue teaching.

PMID- 19116477
TI  - E-learning as evidence of educational scholarship: a survey of chairs of
      promotion and tenure committees at U.S. medical schools.
AB  - PURPOSE: To ascertain the attitudes of chairs of U.S. medical school promotion
      committees toward e-learning and how their institutions recognize and reward
      faculty for e-learning as a scholarly activity. METHOD: In 2007, the authors
      mailed a questionnaire to chairs of promotion and tenure committees at 123 U.S.
      medical schools. Chairs rated the importance of major areas of clinician
      educators' e-learning performance using a five-point scale (1 = not important; 5
      = extremely important). In another section, chairs rated the quality of
      information that is usually available to evaluate faculty performance in e
      learning scholarship using a five-point scale (1 = low quality; 5 = excellent).
      Respondents were also able to enter qualitative comments about the role of e
      learning and educational scholarship at their institution. Frequency
      distributions for each question were examined to identify any irregularities in
      the data, and descriptive statistics were used to summarize responses to
      questions. Themes were extracted from the qualitative data. RESULTS: The response
      rate to the survey was 51% (63/123). Fifty-six (88.8%) participants indicated
      that educational scholarship was at least moderately important to a candidate's
      chances of promotion. Forty-eight (76%) respondents recognized e-learning as a
      meaningful contribution to scholarship. The chairs rated several levels of
      evaluation as well as types of e-learning activities and products: changing
      learner outcomes, developing and disseminating materials, authoring publications,
      receiving grant awards, serving on editorial boards, and directing a program.
      CONCLUSIONS: Promotion chairs value selected e-learning activities and products
      as evidence of teaching scholarship.

PMID- 19116478
TI  - Pain overlooked--imperfect technology.

PMID- 19116479
TI  - Evaluating the performance of medical educators: a novel analysis tool to
      demonstrate the quality and impact of educational activities.
AB  - PURPOSE: Traditional promotion standards rely heavily on quantification of
      research grants and publications in the curriculum vitae. The promotion and
      retention of educators is challenged by the lack of accepted standards to
      evaluate the depth, breadth, quality, and impact of educational activities. The
      authors sought to develop a practical analysis tool for the evaluation of
      educator portfolios (EPs), based on measurable outcomes that allow reproducible
      analysis of the quality and impact of educational activities. METHOD: The
      authors, 10 veteran educators and an external expert evaluator, used a scholarly,
      iterative consensus-building process to develop the tool and test it using real
      EPs from educational scholars who followed an EP template. They revised the
      template in parallel with the analysis tool to ensure that EP data enabled valid
      and reliable evaluation. The authors created the EP template and analysis tool
      for scholar and program evaluation in the Educational Scholars Program, a three
      year national certification program of the Academic Pediatric Association.
      RESULTS: The analysis tool combines 18 quantitative and 25 qualitative items,
      with specifications, for objective evaluation of educational activities and
      scholarship. CONCLUSIONS: The authors offer this comprehensive, yet practical
      tool as a method to enhance opportunities for faculty promotions and advancement,
      based on well-defined and documented educational outcome measures. It is relevant
      for clinical educators across disciplines and across institutions. Future studies
      will test the interrater reliability of the tool, using data from EPs written
      using the revised template.

PMID- 19116480
TI  - Medical school deans' perceptions of organizational climate: useful indicators
      for advancement of women faculty and evaluation of a leadership program's impact.
AB  - PURPOSE AND METHOD: The authors surveyed U.S. and Canadian medical school deans
      regarding organizational climate for faculty, policies affecting faculty,
      processes deans use for developing faculty leadership, and the impact of the
      Executive Leadership in Academic Medicine (ELAM) Program for Women. RESULTS: The
      usable response rate was 58% (n = 83/142). Deans perceived gender equity in
      organizational climate as neutral, improving, or attained on most items and
      deficient on four. Only three family-friendly policies/benefits were available at
      more than 68% of medical schools; several policies specifically designed to
      increase gender equity were available at fewer than 14%. Women deans reported
      significantly more frequent use than men (P = .032) of practices used to develop
      faculty leadership. Deans' impressions regarding the impact of ELAM alumnae on
      their schools was positive (M = 5.62 out of 7), with those having more fellows
      reporting greater benefit (P = .01). The deans felt the ELAM program had a very
      positive influence on its alumnae (M = 6.27) and increased their eligibility for
      promotion (M = 5.7). CONCLUSIONS: This study provides a unique window into the
      perceptions of medical school deans, important policy leaders at their
      institutions. Their opinion adds to previous studies of organizational climate
      focused on faculty perceptions. Deans perceive the organizational climate for
      women to be improving, but they believe that certain interventions are still
      needed. Women deans seem more proactive in their use of practices to develop
      leadership. Finally, deans provide an important third-party judgment for program
      evaluation of the ELAM leadership intervention, reporting a positive impact on
      its alumnae and their schools.

PMID- 19116482
TI  - A time for change: an exploration of attitudes toward part-time work in academia
      among women internists and their division chiefs.
AB  - BACKGROUND: Increasing numbers of clinicians desire part-time work, and many will
      opt out of academic medicine if the barriers to part-time work are too great.
      METHOD: Purposeful sampling was used to investigate the experiences of part-time
      academic physicians and their division leaders to understand (1) how each
      identified the negative and positive consequences of part-time work, and (2) how
      each conceptualize part-time work. In 2004, the authors interviewed the Society
      of General Medicine Horn Scholars Program applicants and their division chiefs
      from the 2001 and 2004 award cycles and performed a qualitative analysis of the
      one- to two-hour audiotaped interviews. RESULTS: Seven out of nine eligible
      applicants and six of seven division chiefs participated. All applicants were
      female junior faculty clinician educators in academic internal medicine from
      seven institutions. All division chiefs were male full-time faculty members. Both
      applicants and division chiefs identified multiple specific negative and positive
      consequences of part-time work. Analysis of interviews suggested that both groups
      tended to frame part-time work as a decision to "work less" or to "work
      differently." Self-reflection and articulation of values helped some faculty
      determine where they derive the greatest happiness and fulfillment personally and
      professionally. CONCLUSIONS: As more academics seek work-life balance and
      consider part-time work as a tool to achieve that balance, academic medicine will
      be challenged to develop creative models for integrating successful part-time
      physicians, or it will lose that segment of the workforce. This study's findings
      suggest that one such model may require that physicians and their leaders
      reconceptualize work altogether.

PMID- 19116483
TI  - Organizational climate and family life: how these factors affect the status of
      women faculty at one medical school.
AB  - PURPOSE: To compare men and women faculty's family situations and perceptions of
      organizational climate. METHOD: In 2005, the authors sent an electronic survey to
      full-time faculty at the University of Minnesota Medical School to assess their
      perceptions of professional relationships, mentoring, obstacles to satisfaction,
      policies, circumstances that contribute to departure, gender equality, family
      situations, and work life. RESULTS: Of 615 faculty, 354 (57%) responded. Women
      and men were equally productive and worked similar total hours. Women were less
      likely to have partners/spouses, were more likely to have partners/spouses who
      were employed, and devoted more time to household tasks. Compared with men, women
      reported more experience with obstacles to career success and satisfaction and
      with circumstances that contribute to departure. More women than men perceived
      that they were expected to represent the perspective of their gender, that they
      were constantly under scrutiny by colleagues, that they worked harder than
      colleagues worked in order to be perceived as legitimate, and that there were
      "unwritten rules" and bias against women. Few faculty reported overt
      discrimination; however, more women than men perceived gender discrimination in
      promotion, salary, space/resources, access to administrative staff, and graduate
      student/fellow assignment. CONCLUSIONS: Work-life and family-life factors served
      as obstacles to satisfaction and retention of the women faculty studied. Many of
      these factors reflect challenges attributable to subtle gender bias and the
      intersection of work and family life. The authors provide examples showing that
      medical schools can implement policy changes that support faculty who must
      balance work and family responsibilities. Identification and elimination of
      gender bias in areas such as promotion, salary, and resource allocation is
      essential.

PMID- 19116486
TI  - A study of the relational aspects of the culture of academic medicine.
AB  - PURPOSE: The impact of medical school culture on medical students has been well
      studied, but little documentation exists regarding how medical faculty experience
      the culture in which they work. In an ongoing project, the National Initiative on
      Gender, Culture and Leadership in Medicine, the authors are investigating how the
      existing culture of academic medical institutions supports all faculty members'
      ability to function at their highest potential. METHOD: The authors conducted a
      qualitative study of faculty in five disparate U.S. medical schools. Faculty in
      different career stages and diverse specialties were interviewed regarding their
      perceptions and experiences in academic medicine. Analysis was inductive and data
      driven. RESULTS: Relational aspects of the culture emerged as a central theme for
      both genders across all career categories. Positive relationships were most
      evident with patients and learners. Negative relational attributes among faculty
      and leadership included disconnection, competitive individualism, undervaluing of
      humanistic qualities, deprecation, disrespect, and the erosion of trust.
      CONCLUSIONS: The data suggest that serious problems exist in the relational
      culture and that such problems may affect medical faculty vitality,
      professionalism, and general productivity and are linked to retention. Efforts to
      create and support trusting relationships in medical schools might enhance all
      faculty members' efforts to optimally contribute to the clinical, education, and
      research missions of academic medicine. Future work will document the outcomes of
      a five-school collaboration to facilitate change in the culture to support the
      productivity of all medical faculty.

PMID- 19116484
TI  - Improving the diversity climate in academic medicine: faculty perceptions as a
      catalyst for institutional change.
AB  - PURPOSE: To assess perceptions of underrepresented minority (URM) and majority
      faculty physicians regarding an institution's diversity climate, and to identify
      potential improvement strategies. METHOD: The authors conducted a cross-sectional
      survey of tenure-track physicians at the Johns Hopkins University School of
      Medicine from June 1, 2004 to September 30, 2005; they measured faculty
      perceptions of bias in department/division operational activities, professional
      satisfaction, career networking, mentorship, and intentions to stay in academia,
      and they examined associations between race/ethnicity and faculty perceptions
      using multivariate logistic regression. RESULTS: Among 703 eligible faculty, 352
      (50.1%) returned surveys. Fewer than one third of respondents reported
      experiences of bias in department/division activities; however, URM faculty were
      less likely than majority faculty to believe faculty recruitment is unbiased
      (21.1% versus 50.6%, P = .006). A minority of respondents were satisfied with
      institutional support for professional development. URM faculty were nearly four
      times less likely than majority faculty to report satisfaction with racial/ethnic
      diversity (12% versus 47.1%, P = .001) and three times less likely to believe
      networking included minorities (9.3% versus 32.6%, P = .014). There were no
      racial/ethnic differences in the quality of mentorship. More than 80% of
      respondents believed they would be in academic medicine in five years. However,
      URM faculty were less likely to report they would be at their current institution
      in five years (42.6% versus 70.5%, P = .004). CONCLUSIONS: Perceptions of the
      institution's diversity climate were poor for most physician faculty and were
      worse for URM faculty, highlighting the need for more transparent and diversity
      sensitive recruitment, promotion, and networking policies/practices.

PMID- 19116487
TI  - La clinica--a doctor's journey across borders: [Excerpt].

PMID- 19116488
TI  - La clinica--a doctor's journey across borders. Commentary.

PMID- 19116489
TI  - A good clinician and a caring person: longitudinal faculty development and the
      enhancement of the human dimensions of care.
AB  - PURPOSE: To successfully design and implement longitudinal faculty development
      programs at five medical schools, and to determine whether faculty participants
      were perceived to be more effective humanistic teachers. METHOD: Promising
      teachers were chosen from volunteers to participate in groups at each of the
      medical schools. Between September 2004 and September 2006, the facilitators
      jointly designed and implemented a curriculum for enhancing humanistic teaching
      using previously defined learning goals that combined experiential learning of
      skills with reflective exploration of values. Twenty-nine participants who
      completed 18 months of faculty development at the five medical schools were
      compared with 47 controls drawn from the same schools in the final six months of
      the two-year project. For comparison, the authors developed a 10-item
      questionnaire, the Humanistic Teaching Practices Effectiveness Questionnaire
      (HTPE), to be filled out by medical students and residents taught by participants
      or control faculty. Items were designed to measure previously identified themes
      and domains of humanism. Control faculty were similar to participants by gender,
      specialty, and years of experience. RESULTS: Thirty-four (75%) of the original 45
      enrollees completed the programs at the five schools. Faculty participants
      outperformed their peer controls on all 10 items of the HTPE questionnaire.
      Results were statistically significant (P < .05) and sufficiently robust (8%-13%
      differences) to suggest practical importance. CONCLUSIONS: A longitudinal faculty
      development process that combines experiential learning of skills and reflective
      exploration of values in the setting of a supportive group process was
      successfully accomplished and had a positive impact on participants' humanistic
      teaching.

PMID- 19116490
TI  - I thought we weren't supposed to do that?

PMID- 19116491
TI  - Evolving curriculum design: a novel framework for continuous, timely, and
      relevant curriculum adaptation in faculty development.
AB  - The time lag between needs assessment and implementation of faculty development
      curricula assumes a certain stability of participants' individual and contextual
      needs which may not reflect the often complex and shifting priorities in health
      professional schools. In addition to the variability of issues they face,
      participants are typically better able to recognize and articulate their needs
      once engaged in a curriculum.This article is a conceptual description of how
      applying an umbrella strategy to curriculum design illuminated an iterative
      methodology for continuous adaptation of the 2004-2006 University of Toronto
      Education Scholars Program in real time to the emergent needs of participants and
      their context. The general goals or umbrella for the core curriculum were
      determined by a broad-based environmental scan. In keeping with a learner
      centered collaborative program, a number of process strategies were developed to
      solicit input from participants during the two years of the program. These
      included creating a dialogue space, use of class and program evaluations,
      modified Delphi needs assessments, and opinion leader interviews. Adaptation of
      curriculum was enabled by protection of curriculum time and flexibility of course
      leadership. The application of strategy theory to curriculum design has not been
      previously described. This iterative approach enabled course leadership to
      successfully identify multiple unperceived issues to address. With this unique
      and cyclical process, curricular relevance and timeliness are ensured as well as
      enhancing participant motivation and engagement, consistent with adult learning
      principles. This methodology should be considered by course directors of all
      continuing professional development programs.

PMID- 19116492
TI  - Not so black and white after all.

PMID- 19116493
TI  - Issues in the mentor-mentee relationship in academic medicine: a qualitative
      study.
AB  - PURPOSE: To explore the phenomenon of the mentor-mentee relationship and to
      characterize this relationship among people who have obtained early career
      support from a government funding agency, in order to facilitate the development
      of future mentorship programs. METHOD: A qualitative study was completed
      involving clinician scientists who were awarded early career support from a
      provincial funding agency (Alberta Heritage Foundation for Medical Research,
      Edmonton, Alberta, Canada) and their mentors. Individual, semistructured
      interviews were completed, and transcripts of interviews were analyzed using a
      grounded theory approach. RESULTS: Interviews with 21 population health or
      clinician investigators (mentees) and seven mentors were completed from October
      to December 2006. Several themes were identified including the experience with
      mentorship, experience of being assigned a mentor versus self-identification,
      roles of a mentor, characteristics of good mentoring, barriers to mentorship, and
      possible mentorship strategies. Participants believed mentorship to be important,
      but several experienced significant difficulty with finding mentors and
      establishing productive relationships. CONCLUSIONS: Challenges exist within
      academic medicine around ensuring that clinician scientists receive appropriate
      mentorship. Strategies to enhance the mentorship process were identified,
      including the development of formal mentorship initiatives, the creation of
      workshops organized by funding agencies in partnership with universities, and the
      development and evaluation of a mentorship training initiative for mentors and
      mentees. These findings can be applied to any academic health sciences
      institution.

PMID- 19116494
TI  - Making the most of mentors: a guide for mentees.
AB  - Effective mentorship is likely one of the most important determinants of success
      in academic medicine and research. Many papers focus on mentoring from the
      mentor's perspective, but few give guidance to mentees forging these critically
      important relationships. The authors apply "managing up," a corporate concept, to
      academic medical settings both to promote effective, successful mentoring and to
      make a mentor's job easier. Managing up requires the mentee to take
      responsibility for his or her part in the collaborative alliance and to be the
      leader of the relationship by guiding and facilitating the mentor's efforts to
      create a satisfying and productive relationship for both parties. The authors
      review the initiation and cultivation of a mentoring relationship from the
      perspective of a mentee at any stage (student through junior faculty), and they
      propose specific strategies for mentee success.

PMID- 19116495
TI  - AM Last Page: U.S. medical school faculty.

PMID- 19116496
TI  - Long-term exposure to road traffic noise and myocardial infarction.
AB  - BACKGROUND: An association has been reported between long-term exposure to road
      traffic noise and the risk of myocardial infarction (MI), but the evidence is
      limited and inconclusive. No previous study has simultaneously analyzed the role
      of exposure to noise and air pollution from road traffic in the risk of MI.
      METHODS: A population-based case-control study on MI was conducted 1992-1994 in
      Stockholm County. Participants answered a questionnaire and underwent a physical
      examination. Residential exposure to noise and air pollution from road traffic
      between 1970 and 1992-1994 was assessed for 3666 participants (1571 cases of MI
      and 2095 controls), based on residential history combined with information on
      traffic intensity and distance to nearby roads. Information was also obtained on
      factors potentially affecting the relationship between noise exposure and MI,
      such as noise annoyance. RESULTS: The correlation between long-term individual
      exposure to noise and air pollution from traffic was high (r = 0.6). The adjusted
      odds ratio for MI associated with long-term road traffic noise exposure of 50 dBA
      or higher was 1.12 (95% confidence interval = 0.95-1.33). In a subsample, defined
      by excluding persons with hearing loss or exposure to noise from other sources,
      the corresponding odds ratio was 1.38 (1.11-1.71), with a positive exposure
      response trend. No strong effect modification was apparent by sex or
      cardiovascular risk factors, including air pollution from road traffic.
      CONCLUSIONS: The results lend some support to the hypothesis that long-term
      exposure to road traffic noise increases the risk for MI.

PMID- 19116497
TI  - Ketamine-associated vomiting: is it dose-related?
AB  - OBJECTIVE: Vomiting is a common adverse event after emergency department ketamine
      sedation in children. We sought to determine if the rate of vomiting is dose
      related to intravenous ketamine. METHODS: Treating physicians administered
      intravenous ketamine to children requiring sedation for a procedure in a
      pediatric emergency department using doses of their discretion in this
      prospective observational study. We compared initial and total ketamine doses
      between children with and without vomiting directly and after controlling for age
      and coadministered drugs using multiple logistic regression analysis. RESULTS: A
      wide range of initial (0.2 to 2.4 mg/kg) and total (0.3 to 23.8 mg/kg) ketamine
      doses were administered in the 1039 sedations studied. Vomiting occurred in 74
      (7%) overall. Initial and total ketamine dose distributions were similar in
      children with and without vomiting (medians 1.6 vs 1.6 mg/kg and 2.2 vs 2.1
      mg/kg, respectively). Our multivariate analysis found no significant association
      between emesis and initial dose; however, it did reveal an association with total
      dose that was explained by a minority (3.5%) of children who received high
      cumulative doses (>7 mg/kg). The rate of emesis was 7.0% when the total ketamine
      dose was 7 mg/kg or less and 11.1% when greater than 7 mg/kg. CONCLUSIONS: Within
      a wide range of intravenous doses, ketamine-associated vomiting is not related to
      either the initial loading dose or the total dose--except for a modest increase
      for those receiving high cumulative doses (>7 mg/kg).

PMID- 19116498
TI  - Occurrence of serious bacterial infection in infants aged 60 days or younger with
      an apparent life-threatening event.
AB  - OBJECTIVE: To describe the occurrence of serious bacterial infections (SBIs) in
      well-appearing, afebrile infants aged 60 days or younger with an apparent life
      threatening event (ALTE). STUDY DESIGN: We retrospectively reviewed microbiologic
      testing in a cohort of well-appearing, afebrile infants aged 60 days or younger
      who presented with an ALTE to a children's hospital emergency department between
      January 2002 and July 2005. All patients were admitted and followed up for 6
      months. Comparisons were made among those who did and did not undergo
      microbiologic testing and full sepsis evaluation (blood, urine, and cerebrospinal
      fluid) and those who did and did not have an SBI. RESULTS: Of 182 patients, 112
      (61.5%) underwent microbiologic testing, and 53 (29.1%) had a full sepsis
      evaluation. Five patients (2.7%; 95% confidence interval, 0.9%-6.3%) had an SBI
      including 3 positive results in blood cultures, 1 positive result in urine
      culture, and 1 positive result for pertussis by polymerase chain reaction. No
      patient had a positive result in cerebrospinal fluid culture (95% confidence
      interval, 0%-5.7%). Patients with a history of prematurity were more likely to
      have an SBI (6.7% vs. 0.8%, P = 0.04). CONCLUSIONS: Serious bacterial infection
      occurred in 2.7% of well-appearing, afebrile infants aged 60 days or younger with
      an ALTE. Prematurity was associated with having an SBI. For premature infants
      aged 60 days or younger who present with an ALTE, an evaluation for SBI should be
      strongly considered.

PMID- 19116499
TI  - Pattern of pediatric zolpidem ingestions reported to Texas poison control
      centers, 2000 to 2006.
AB  - OBJECTIVES: The purpose of this study was to describe the pattern of zolpidem
      ingestions by young children reported to poison control centers. METHODS: Cases
      were all zolpidem ingestions by children 0 to 5 year old reported to Texas poison
      control centers during 2000 to 2006. Multiple substance ingestions were excluded.
      The distribution of cases was described with respect to such demographic and
      clinical factors as patient gender, ingestion reason, ingestion site, management
      site, and medical outcome. RESULTS: There were a total of 463 cases, all
      unintentional exposures. The patient was male in 52.2% of the cases, and the
      exposure occurred at the patient's own home in 92.8% of the cases. The patient
      was managed on-site in 54.4% cases, already at or en route to a health care
      facility in 29.6% cases, and referred to a health care facility in 16.0% cases.
      Of the 322 cases with a known final medical outcome, 59.0% had no effect, 35.1%
      had minor effects, and 5.9% had moderate effects. CONCLUSIONS: Pediatric
      ingestions of zolpidem alone reported to Texas poison control centers most
      frequently resulted in at most minor effects and were often managed at home.

PMID- 19116500
TI  - Fever determination in young infants: prevalence and accuracy of parental
      palpation.
AB  - OBJECTIVES: Pediatricians routinely advise parents to seek immediate medical
      attention if their young infant develops a fever. Many parents rely on palpation
      to assess their child's temperature. Our objective was to determine the
      prevalence and accuracy of parental palpation for fever in young infants.
      METHODS: We enrolled a convenience sample of infants younger than 3 months
      presenting to a pediatric emergency department with any complaint. Parents
      answered questions regarding their usual fever determination practices and
      palpated their infants to assess for fever. Parental predictions were then
      compared with the standard rectal temperature obtained at triage. RESULTS: Ninety
      six infants were enrolled. Fifty-seven percent of parents reported palpation as a
      usual method of fever assessment, with 87% palpating for fever at least
      occasionally. Of the 78% of parents who owned a thermometer, nearly half used
      palpation regularly. As compared with the "gold standard" of rectal thermometry,
      parental palpation for fever had a sensitivity of 81%, specificity of 82%,
      positive predictive value of 59% and negative predictive value of 93%. After
      eliminating from analysis those infants whose parents had used a thermometer at
      home, we found a sensitivity of 67%, specificity of 84%, positive predictive
      value of 33%, and negative predictive value of 95%. CONCLUSIONS: Many parents
      rely on palpation as a usual method of fever determination in young infants,
      including nearly half of those who own a thermometer. Parental palpation
      overestimates the presence of fever, but is likely to be accurate when parents
      report that their baby is not febrile. As a sole method of determining fever,
      parental palpation is unreliable.

PMID- 19116501
TI  - Radiographic pneumonia in young, highly febrile children with leukocytosis before
      and after universal conjugate pneumococcal vaccination.
AB  - OBJECTIVES: Studies before the introduction of conjugate pneumococcal vaccine
      demonstrated a high rate of radiographic pneumonia among highly febrile young
      children with leukocytosis and no other identified source of infection. We sought
      to evaluate the impact of universal vaccination with Prevnar (pneumococcal
      conjugate vaccine [PCV]) on the incidence and characteristics of occult and
      nonoccult radiographic pneumonia among these children. METHODS: Retrospective
      cohort study of children younger than 5 years seen in an urban pediatric
      emergency department with temperature 39 degrees C or higher, white blood cell
      count 20,000/microL or higher, and chest radiograph performed. Pneumonia was
      defined as focal infiltrate or consolidation on chest radiograph as read by an
      attending radiologist. Occult pneumonia was defined as radiographic pneumonia in
      the absence of lower respiratory tract signs or cough. RESULTS: Before universal
      pneumococcal vaccination, radiographic pneumonia was found in 190 (21%) of 889
      (95% confidence interval [CI], 19-24) eligible children compared with 61 (18%) of
      335 (95% CI: 14, 23) eligible children after universal vaccination (P = 0.27).
      Occult pneumonia was identified in 61 (15%) of 404 (95% CI, 12-19) pre-PCV
      compared with 13 (9%) of 147 (95% CI, 5-15) post-PCV (P = 0.07). In children
      younger than 2 years, radiographic pneumonia was identified in 121 (17%) of 709
      (95% CI, 14-20) pre-PCV and 26 (10%) of 254 (95% CI, 7-15) post-PCV (P = 0.01).
      CONCLUSIONS: Clinicians should continue to consider chest radiography in young
      highly febrile children with leukocytosis and no other identified source of
      infection.

PMID- 19116505
TI  - AlloDerm versus DermaMatrix in immediate expander-based breast reconstruction: a
      preliminary comparison of complication profiles and material compliance.
AB  - BACKGROUND: Allogenic acellular dermal matrix can be used in single-stage,
      expander-based immediate and delayed breast reconstructions to provide
      inferolateral prosthesis coverage and reconstruction of the inframammary fold.
      Two allogenic dermal matrix products currently available, AlloDerm and
      DermaMatrix, differ in method of storage, cost, and intraoperative preparation.
      The purpose of this study was to determine, first, whether there are any
      significant differences in the rates of postoperative complications, material
      compliance, or capsule characteristics; and second, if differences are present,
      whether they had any impact on final outcome. METHODS: After institutional review
      board approval, a retrospective analysis of prospectively collected data of 30
      patients (50 breasts) who underwent immediate expander-based breast
      reconstructions using either AlloDerm (n = 25) or DermaMatrix (n = 25) dermal
      substitutes was performed. Primary endpoints were (1) incidence of seroma, (2)
      wound infection, (3) number of days requiring drains, (4) rate of tissue
      expansion, (5) final expanded volume, (6) final implant volume, and (7)
      neovascularization. RESULTS: The mean follow-up was 6.7 months. During this time,
      no significant differences in the complication profile were found between the two
      groups. Both dermal substitutes were found to be well incorporated, with evidence
      of neovascularization, on histologic examination. CONCLUSIONS: This study
      demonstrated no significant differences in the rate of complications or material
      compliance. The total complication rate was 4 percent, with seroma and wound
      infection being the most common complications. The authors' preliminary findings
      indicate no significant difference between implant/expander-based reconstructions
      using AlloDerm and those using DermaMatrix.

PMID- 19116502
TI  - Simple febrile seizures: are the AAP guidelines regarding lumbar puncture being
      followed?
AB  - BACKGROUND: In 1996, the American Academy of Pediatrics (AAP) published a
      practice parameter recommending that lumbar puncture (LP) be strongly considered
      in infants younger than 12 months presenting with a first febrile seizure.
      OBJECTIVE: We sought: (1) to determine if the recommendations of the AAP are
      being followed by pediatric emergency medicine-trained physicians at our
      institution; (2) to describe the rate of meningitis among patients with febrile
      seizure who underwent LP; and (3) to determine if there were differences in
      performance of LP if children were younger or pretreated with antibiotics.
      METHODS: A retrospective chart review of patients aged 6 to 12 months presenting
      with first simple febrile seizure to the emergency department (ED) at Miami
      Children's Hospital was conducted between January 2001 and November 2005.
      RESULTS: A total of 242 ED records with a discharge diagnosis including the term
      "febrile seizure," "seizure," or "meningitis" were identified. Of those, 56 met
      inclusion criteria for first simple febrile seizure. Lumbar puncture was
      performed in 28 patients (50%) that met inclusion criteria. Younger patients were
      no more likely to have LP performed than older patients (P = 0.15). Ten children
      (17.8%) received antibiotics before the ED visit; of these, 4 (40%) underwent LP
      in the ED. Children who presented with first simple febrile seizure to our
      institution who were pretreated with antibiotics were no more likely to have LP
      performed than those who were not receiving antibiotics (P = 0.48). All
      cerebrospinal fluid cultures were sterile. CONCLUSION: The AAP recommendations
      regarding LP in patients 6 to 12 months of age with first simple febrile seizure
      are not being strictly adhered to. The AAP recommendations regarding simple
      febrile seizures were conceived in a different epidemiologic era of disease
      pathology with data not representative of current prevalence and etiologic issues
      and need to be revisited.

PMID- 19116506
TI  - Satisfactory reconstruction with autologous costal cartilage graft in a geriatric
      microtia patient.

PMID- 19116508
TI  - Tolerance and future directions for composite tissue allograft transplants: part
      II.
AB  - LEARNING OBJECTIVES: After studying this article, the participant should be able
      to: 1. Discuss the definition and basic aspects of tolerance as applied to
      clinical practice. 2. Understand the role of donor bone marrow cells for
      tolerance induction in composite tissue allograft. 3. Understand the role of
      passenger leukocytes in allograft acceptance and rejection. 4. Understand the
      tolerogenic role of dendritic cells and regulatory cells in composite tissue
      allograft transplants. 5. Understand modern approaches to transplantation
      tolerance and their applicability to composite tissue allograft transplants.
      SUMMARY: The introduction of composite tissue allograft transplants into clinical
      practice has become reality because of well-established microsurgical techniques.
      However, the success of composite tissue allograft transplants is still dependent
      on chronic immunosuppression. Clinically applicable protocols for tolerance
      induction in composite tissue allograft would eliminate the need for lifelong
      immunosuppression. The major goal of transplantation immunology is to develop
      immunologic nonresponsiveness (tolerance) to allograft transplants and long-term
      drug-free survival. A number of protocols have been designed to develop tolerance
      in experimental systems; however, none of them has been translated to clinical
      transplantation. In this review, the authors discuss current knowledge and
      strategies used for tolerance induction and the role of passenger leukocytes for
      allograft acceptance and rejection. Tolerogenic properties of dendritic cells and
      immunotherapy with regulatory T cells are introduced as having future potential
      for tolerance induction in solid organ and composite tissue allograft
      transplants. The induction of donor-specific tolerance would generate new options
      for the application of composite tissue allograft transplants and may be
      considered as a future direction in plastic and reconstructive surgery.

PMID- 19116509
TI  - The efficacy of prophylactic low-molecular-weight heparin to prevent pulmonary
      thromboembolism in immediate breast reconstruction using the TRAM flap.
AB  - BACKGROUND: Immediate breast reconstruction using the transverse rectus abdominis
      musculocutaneous (TRAM) flap is associated with multiple risk factors for
      pulmonary thromboembolism, the incidence of which has been reported to be as high
      as 6.3 percent. The authors conducted a prospective study of the efficacy of
      prophylactic use of low-molecular-weight heparin to prevent pulmonary
      thromboembolism. METHODS: Six hundred fifty consecutive patients who underwent
      immediate breast reconstruction with TRAM flaps between August of 2001 and April
      of 2007 were included in this study. No medical prophylaxis was administered for
      the former 450 consecutive patients (group 1). Since February of 2006, enoxaparin
      was routinely given to the latter 200 consecutive patients (group 2) for 7 days,
      from the day of surgery. Fifty-four patients in group 1 (group 1c) and 68
      patients in group 2 (group 2c) were routinely examined for asymptomatic pulmonary
      thromboembolism. Incidences of symptomatic and asymptomatic pulmonary
      thromboembolism, decreases in hemoglobin, and bleeding-related complications were
      compared. RESULTS: Although the incidence of symptomatic pulmonary
      thromboembolism did not differ significantly between groups 1 and 2 (1.8 percent
      versus 0 percent; p = 0.107), that of asymptomatic pulmonary thromboembolism was
      significantly higher in group 1c than in group 2c (16.7 percent versus 0 percent;
      p = 0.009). The hemoglobin decrease was significantly different (2.5 g/dl in
      group 1 versus 2.8 g/dl in group 2; p = 0.001), but the incidences of
      transfusion, hematoma, and seroma showed no statistically significant difference.
      CONCLUSION: : Prophylactic use of low-molecular-weight heparin was effective in
      preventing pulmonary thromboembolism without increasing problematic bleeding
      related complications in TRAM flap immediate breast reconstruction patients.

PMID- 19116510
TI  - The pedicled descending branch muscle-sparing latissimus dorsi flap for breast
      reconstruction.
AB  - BACKGROUND: The pedicled descending branch muscle-sparing latissimus dorsi flap
      with a transversely oriented skin paddle presents distinct advantages in breast
      reconstruction, including reduced donor-site morbidity and greater freedom of
      orientation of the skin paddle. This study reports the anatomical basis, surgical
      technique, complications, and aesthetic and functional outcomes following use of
      this flap for breast reconstruction. METHODS: A retrospective study of 20
      patients who underwent breast reconstruction with a pedicled muscle-sparing
      latissimus dorsi musculocutaneous flap was conducted. Indications for surgery
      included breast reconstruction following mastectomy, lumpectomy, and irradiation,
      and for correction of implant-related complications. Case-note review was
      performed, as was a functional evaluation consisting of a patient questionnaire,
      a Disabilities of the Arm, Shoulder, and Hand form, postoperative range-of-motion
      analysis, and instrumented strength testing comparing the operated and
      nonoperated sides. Aesthetic evaluation of the donor site was conducted by all
      patients. An anatomical study of 15 flaps harvested from fresh cadavers was
      performed to determine the location of the bifurcation of the thoracodorsal
      artery and the course of its descending branch. RESULTS: Twenty-four descending
      branch muscle-sparing latissimus dorsi flaps were harvested. All donor sites were
      closed primarily, with skin paddle sizes ranging up to 25 x 12 cm. There was one
      case of minor flap tip necrosis and no instances of seroma. There was no
      statistically significant difference in strength or range of motion of the
      shoulder joint when comparing the operated to the nonoperated side. Two patients
      reported minor functional impact following surgery. CONCLUSIONS: The pedicled
      descending branch muscle-sparing latissimus dorsi flap with a transversely
      orientated skin paddle results in minimal functional deficit of the donor site,
      absence of seroma, large freedom of orientation of the skin paddle, low rate of
      flap complications, and a cosmetically acceptable scar.

PMID- 19116511
TI  - Unilateral superficial musculoaponeurotic system plication in facial
      reconstructive surgery.

PMID- 19116512
TI  - Vacuum-assisted closure for wound dehiscence in head and neck reconstruction.

PMID- 19116513
TI  - Regional lymphatic dissemination of squamous cell carcinoma of the face.

PMID- 19116514
TI  - Use of platelet gel in Romberg syndrome.

PMID- 19116515
TI  - New concepts related to the tarsus and orbicularis oculi muscle.

PMID- 19116516
TI  - Keeping options open for patients with anticipated postmastectomy chest wall
      irradiation: immediate tissue expansion followed by reconstruction of choice.

PMID- 19116517
TI  - Chondrodermatitis nodularis auricularis: a new name for an old disease.

PMID- 19116518
TI  - Utilization of aquamid as a filler for rhinoplasty in orientals.

PMID- 19116519
TI  - Treatment of bilateral condylar fractures of the mandible with distraction
      osteogenesis device.

PMID- 19116520
TI  - A novel method for neurotization of deep inferior epigastric perforator and
      superficial inferior epigastric artery flaps.

PMID- 19116521
TI  - A modified skin pattern of reduction mammaplasty for wide local excision, or skin
      sparing mastectomy in superficial breast tumors, where skin excision is required.

PMID- 19116523
TI  - Subfascial breast augmentation: thickness of the pectoral fascia.

PMID- 19116522
TI  - Differential effects of TGF-beta1 and TGF-beta3 on chondrogenesis in
      posterofrontal cranial suture-derived mesenchymal cells in vitro.
AB  - BACKGROUND: Transforming growth factor (TGF)-beta1 has been associated with
      cranial suture fusion, whereas TGF-beta3 has been associated with suture patency.
      The mouse posterofrontal suture, analogous to the human metopic suture, fuses
      through endochondral ossification. METHODS: TGF-beta1 and TGF-beta3 expression in
      the posterofrontal suture was examined by immunohistochemistry. Next, the authors
      established cultures of suture-derived mesenchymal cells from the posterofrontal
      suture and examined the cellular responses to TGF-beta1 and TGF-beta3.
      Proliferation in response to TGF-beta isoforms was examined by bromodeoxyuridine
      incorporation. High-density micromass culture of posterofrontal mesenchymal cells
      was used to study the effect of TGF-beta1 and TGF-beta3 on chondrogenic
      differentiation. RESULTS: TGF-beta1 but not TGF-beta3 protein was highly
      expressed in chondrocytes within the posterofrontal suture. Significant increases
      in posterofrontal cell proliferation were observed with TGF-beta3 but not TGF
      beta1. TGF-beta1 led to significant increases in chondrogenic-specific gene
      expression (including Sox9, Col II, Aggrecan, and Col X) as compared with
      moderate effects of TGF-beta3. TGF-beta1 increased cellular adhesion molecule
      expression (N-cadherin and fibronectin) and promoted cellular condensation,
      whereas TGF-beta3 increased cellular proliferation (PCNA expression). Finally,
      TGF-beta1 and, to a lesser extent, TGF-beta3 induced the expression of fibroblast
      growth factors (FGF-2 and FGF-18). CONCLUSIONS: TGF-beta1 and TGF-beta3 exhibit
      marked differences in their effects on chondrogenesis in posterfrontal suture
      derived mesenchymal cells, influencing different stages of chondrogenic
      differentiation. TGF-beta3 significantly increased cellular proliferation,
      whereas TGF-beta1 induced precartilage condensation, promoting chondrocyte
      differentiation.

PMID- 19116524
TI  - Sensory nerves in the lower pole of the breast encountered in breast
      (augmentation) surgery.

PMID- 19116525
TI  - Sweat gland carcinoma.

PMID- 19116526
TI  - Total subperiosteal approach to suprascapular nerve decompression: a technique to
      relieve entrapment by the superior transverse suprascapular ligament.

PMID- 19116527
TI  - Reoperative digital sympathectomy in refractory Raynaud's phenomenon.

PMID- 19116528
TI  - Botox to the rescue.

PMID- 19116529
TI  - Toe-to-hand transplantation after failed osteogenesis distraction: a "peg-in-cup"
      osteosynthesis.

PMID- 19116530
TI  - Intraneural lipoma of the ulnar nerve.

PMID- 19116531
TI  - The role of antibiotic prophylaxis in abdominoplasty: a review of the infection
      rate in 300 cases treated without prophylaxis.

PMID- 19116532
TI  - A modified model for rat sciatic nerve ischemia/reperfusion injury.

PMID- 19116533
TI  - Neurovascular anatomy of sartorius muscle flaps: implications for local
      transposition and facial reanimation.
AB  - BACKGROUND: The sartorius muscle is a superficial muscle of the thigh that
      possesses highly suitable qualities for many uses in local transposition and free
      muscle transfer. However, a paucity of description of the neurovascular anatomy
      of the sartorius has contributed to its infrequent use in these roles. METHODS:
      Both human and canine studies were undertaken to delineate the neurovascular
      anatomy of the sartorius and to determine the role for surgical delay clinically.
      Fifty-five human cadaveric sartorius muscles and 30 canine cadaveric sartorius
      muscles underwent angiographic and dissection studies, and the location and
      course of the vessels and nerves supplying sartorius are described. A subsequent
      study was undertaken in two live canines in which the vascular supply to the
      sartorius was evaluated before and after surgical delay. RESULTS: The sartorius
      is supplied by an average of six or seven vascular pedicles, the size, location,
      and course of which are described. The nerve supply to the sartorius enters at
      its proximal end and uniformly arises from a branch of the femoral nerve.
      Variations in branching patterns and course of nerves and vessels are described.
      Living canine studies demonstrated the dilatation of intramuscular vessels
      following surgical delay, with the contrast injection of a single remaining
      vascular pedicle shown to vascularize the entire length of the sartorius muscle.
      CONCLUSIONS: The sartorius is highly suitable for local transposition and free
      muscle transfer for facial reanimation. The neurovascular anatomy is reliable,
      and the use of surgical delay can augment its vascular supply and increase the
      arc of rotation for local transposition.

PMID- 19116534
TI  - Successful repair of symptomatic extremity muscle herniation with synthetic mesh.

PMID- 19116535
TI  - New technique for ligation of branches in microsurgery.

PMID- 19116536
TI  - Comparative analysis of the influence of perichondrium on conjunctival
      epithelialization on conchal cartilage grafts in eyelid reconstruction:
      experimental study in rabbits.
AB  - BACKGROUND: Although the role of cartilage grafts in reconstruction of the
      posterior eyelid lamella is well established, spontaneous conjunctival
      epithelialization on such grafts has yet to be fully proven. The aim of this
      study was to perform a comparative analysis of the influence of perichondrium on
      conjunctival epithelialization over conchal cartilage grafts used in eyelid
      reconstruction in rabbits. METHODS: The posterior lamellae of 100 lower eyelids
      from 50 rabbits were reconstructed with autogenous grafts of conchal ear
      cartilage. In the right eyelids, cartilage was grafted with the perichondrium in
      direct contact with the eyeball, and the left eyelids were reconstructed in a
      similar manner but using cartilage grafts without perichondrium. The animals were
      killed after 1, 2, 3, 4, and 5 weeks, and their lower eyelids were analyzed
      macroscopically and histologically. RESULTS: The percentage difference in
      conjunctival epithelialization on the cartilage with perichondrium and that
      without perichondrium was 11.41 percent in the first week of the experiment,
      13.64 percent in the second week, 18.69 percent in the third week, 10.38 percent
      in the fourth week, and 6.17 percent in the fifth week. The average percentage
      conjunctival epithelialization in the eyelids reconstructed with a cartilage
      graft with perichondrium was significantly higher throughout the 5 weeks of the
      experiment than in the eyelids reconstructed with cartilage without perichondrium
      (p < 0.0002). CONCLUSION: It was found that the perichondrium had an important
      role in conjunctival epithelialization in eyelids reconstructed with a cartilage
      graft in the present study.

PMID- 19116537
TI  - Prevention of anastomotic thrombosis by botulinum toxin a in an animal model.
AB  - BACKGROUND: Free tissue transfer is used widely for reconstruction of complex
      defects throughout the body. The most common cause for free flap failure remains
      vascular thrombosis. Currently, there exists no animal model for anastomotic
      vasospasm. Botulinum toxin type A has been successfully used to treat vasospasm
      in Raynaud's phenomenon. A blinded, vasospasm animal model was designed to
      determine its ability to prevent anastomotic thrombosis. METHODS: Ten Sprague
      Dawley-derived rats were pretreated with botulinum toxin type A subcutaneously to
      a randomly determined femoral vessel. Animals acted as their own controls,
      receiving saline to the contralateral limb. Five days postoperatively, femoral
      vessels were measured to determine the effect of neuromuscular blockade on
      diameter. Vessels were then divided and reanastomosed. Animals were subjected to
      a systemic treatment with a peripheral vasoconstrictor, phenylephrine, and a
      lower extremity thermic challenge in an ice bath. Vessel patency was recorded
      before cold challenge and 1 hour after. RESULTS: Vessel diameter was consistently
      larger in all neuromuscularly blocked vessels. The botulinum toxin type A-treated
      arterial average was significantly larger than the matched control average, and
      the venous average was significantly larger than the matched control average.
      Difficulty of anastomosis and time of suturing were significantly less in the
      pretreated botulinum toxin type A group. Patency was maintained in 100 percent of
      vessels treated with botulinum toxin type A and in 44 percent of saline-treated
      vessels at 1 hour after vasospastic challenge. CONCLUSIONS: Botulinum toxin type
      A was successful in preventing thrombosis within this model. Its ability to
      decrease vasospasm and thrombosis may have applications for improving free flap
      survival in select patients.

PMID- 19116538
TI  - Use of vascularized periosteum or bone to improve healing of segmental allografts
      after tumor resection: an ovine rib model.
AB  - BACKGROUND: Despite technical advances, nonunion or delayed union remains an
      important clinical problem when segmental allografts are used to repair
      diaphyseal defects after bone tumor resection. Using an ovine rib model, the
      authors studied whether the addition of a vascularized periosteum or bone flap
      improved healing compared with a segmental allograft alone. METHODS: A 4-cm
      segment of rib was resected from four consecutive ribs of 15 sheep. Three
      different reconstructions were compared within the same sheep: allograft alone,
      allograft and vascularized periosteum, and allograft and vascularized bone. One
      defect was not reconstructed and served as a control. Five sheep were humanely
      killed at each of the following time points: 9, 12, and 15 weeks. The host
      allograft junctions were analyzed using plain radiographs, micro-computed
      tomography, and histologic examination. RESULTS: Micro-computed tomographic
      analysis showed significant improvement with each reconstruction technique over
      time. Plain radiographs and histologic analyses demonstrated earlier bridging of
      the host-allograft junction when either vascularized periosteum or vascularized
      bone was used compared with allograft alone. CONCLUSION: Use of vascularized
      periosteum or bone may facilitate healing of the host-allograft junction after
      intercalary allograft reconstruction.

PMID- 19116539
TI  - Three-dimensional angiography of the superior gluteal artery and lumbar artery
      perforator flap.
AB  - BACKGROUND: Three-dimensional angiography was first proposed by Cornelius and
      advanced by Voigt in 1975. Since then, a variety of improvements have been made.
      The three-dimensional evaluation of perforator flaps is no longer a clinical
      curiosity but an absolute necessity. By combining three-dimensional digital
      imaging and angiography, the authors have developed a new three-dimensional
      technique for visualizing blood vessels. This method produces a digitized model
      of the lumbar artery and superior gluteal artery musculocutaneous perforators
      that enables secure elevation of the lumbar and superior gluteal artery cross
      boundary perforator flap. METHODS: Two cadavers underwent whole body lead oxide
      gelatin injection. Spiral computed tomographic scanning was then performed on the
      cadavers and three-dimensional reconstructions were performed. Six fresh bodies
      were used, and underwent latex injection. Specimens were then dissected by layers
      to document the individual perforators. RESULTS: An average of five superior
      gluteal artery musculocutaneous perforators with a diameter of 0.6 mm were
      present in the specimens. The average diameter and area supplied by perforators
      from the lumbar arteries was 0.7 mm and 30 cm, respectively. The three
      dimensional reconstructed model of the lumbar region can display the modality,
      spatial location, and adjacent relationship of the lumbar and superior gluteal
      arteries. CONCLUSIONS: Three-dimensional modeling of lumbar and superior gluteal
      artery perforator flaps could provide greater insight into perforator anatomy in
      combination with traditional sectional imaging. Three-dimensional reconstructive
      modeling is now a clinically available process which, in the future, could
      provide great value in basic science investigation, clinical training,
      preoperative design, and virtual surgical procedures.

PMID- 19116540
TI  - Refinements in nasal reconstruction: the cross-paramedian forehead flap.
AB  - BACKGROUND: Nasal reconstruction can be a challenge for the plastic surgeon. The
      forehead flap is the workhorse in nasal reconstruction, providing similar skin
      color, texture, structure, and reliability. There are disadvantages of the
      forehead flap, including a difficult arc of rotation, which risks displacement of
      medial eyebrow hair. The vertical design can encroach on the scalp, incorporating
      hair into the nasal reconstruction. Forehead flap inset results in an inverted V
      shaped scar visible in the glabella region. This article describes the authors'
      modification of the established oblique paramedian forehead flap. METHODS: This
      retrospective study included a consecutive series of patients over an 11-year
      period (December of 1996 to December of 2007) that underwent nasal reconstruction
      performed by the primary surgeon (J.A.). Information obtained from chart reviews
      included age, sex, cause of nasal defect, complications, and revisions. RESULTS:
      This study population consisted of 94 adults: 54 men (57 percent) and 40 women
      (43 percent) who underwent nasal reconstruction using the cross-paramedian
      forehead flap. All flaps were performed for skin cancer reconstruction. Partial
      flap loss was the most common complication. Tobacco use was associated with half
      of the complications. Further refinements following forehead flap inset were
      performed in 50 percent of patients. CONCLUSIONS: The cross-paramedian forehead
      flap is a useful design when planning subtotal nasal reconstruction. It provides
      a smooth arc of rotation and increased length, avoids an inverted V-shaped
      glabella scar, and minimizes eyebrow distortion. These modifications of the
      forehead flap maintain the reliability and versatility of the flap and provide an
      aesthetically pleasing result.

PMID- 19116542
TI  - An algorithmic approach to reconstructive surgery and prosthetic rehabilitation
      after orbital exenteration.
AB  - BACKGROUND: The authors' goal was to describe an algorithm for surgical
      reconstruction and prosthetic rehabilitation after orbital exenteration. METHODS:
      A review of 79 patients who underwent orbital exenteration between 1999 and 2007
      was performed. Reconstructions were classified as resulting in an "open" cavity
      when a concave orbital socket facilitating prosthetic retention was created or a
      "closed" cavity when the orbit was filled with soft tissue to the level of the
      orbital rim. RESULTS: Reconstructive procedures included skin grafts (n = 18),
      regional flaps (n = 6), and microvascular free flaps (n = 55). Open cavities were
      created in 34 patients and closed cavities were created in 45 patients. Twenty
      one patients (27 percent) experienced surgical complications. There were no
      significant differences in complication rates among various reconstructive
      techniques (skin graft versus regional flap versus free flap) or types of
      cavities created (open versus closed). Of the 17 patients who use prostheses,
      eight (47 percent) wear their prostheses regularly. Fourteen patients (82
      percent) who received an orbital prosthesis had open cavities (p = 0.001). Thirty
      nine percent of patients with a skin graft received orbital prostheses, and 17
      percent with a regional flap and 15 percent with a free flap received orbital
      prostheses (p = 0.01). CONCLUSIONS: The reconstructive method should be tailored
      to the defect and the patient's needs. When a prosthetic is planned, the goal
      should be to create an open cavity with a skin graft, regional flap, or thin free
      flap. Bulky free flaps are indicated when a closed cavity is preferred, such as
      when no prosthetic is planned or the defect is extensive.

PMID- 19116543
TI  - Wound infection rates in elective plastic surgery for HIV-positive patients.
AB  - BACKGROUND: Human immunodeficiency virus (HIV)-positive patients suffer from a
      unique set of aesthetic challenges, frequently requiring plastic and
      reconstructive surgical intervention. This study was designed to evaluate the
      overall wound infection rates for elective surgery in this patient population,
      focusing specifically on differences between transdermal (both open and minimally
      invasive) and transoral procedures. METHODS: Charts were reviewed for all
      patients with an International Classification of Diseases, Ninth Edition code of
      V08 (asymptomatic HIV infection, CD4 count >200 cells/microl) who underwent
      surgery by the senior author (S.P.D.) at this tertiary care hospital between
      January 1, 2000, and October 1, 2007 (39 patients, 98 procedures). Indication for
      surgery, type of procedure performed, wound infection rates, length of follow-up,
      status of HIV infection, and HIV treatment status were all documented. Data were
      collected according to internal review board protocol. Infection rates were
      compared between study groups and with the existing surgical literature. RESULTS:
      Statistical analysis revealed no significant difference in wound infection rate
      between open and minimally invasive procedures when a transdermal approach is
      used (10 percent and 0 percent, respectively; p > 0.05). However, there was a
      significantly increased infection rate in transoral surgery when compared with
      these two groups (71 percent; p < 0.001). CONCLUSIONS: These findings indicate
      that there is a greatly increased risk of wound infections for HIV-positive
      patients undergoing transoral surgery when compared with transdermal surgery and
      historical norms.

PMID- 19116544
TI  - Corneal neurotization: a novel solution to neurotrophic keratopathy.
AB  - BACKGROUND: This study was designed to evaluate the efficacy of direct corneal
      neurotization using contralateral supraorbital and supratrochlear nerves in
      patients with unilateral facial palsy and corneal anesthesia. A novel surgical
      procedure in which these donor nerve branches are inserted at the contralateral
      anesthetic corneal limbus for sensory neurotization is described. METHODS: The
      charts of six patients were reviewed thoroughly to evaluate changes in corneal
      sensibility following surgery for direct corneal neurotization. Visual acuity,
      blink reflex, donor deficit, synesthesia, long-term corneal health, and several
      psychosocial measures and overall patient satisfaction with the procedure are
      reported. RESULTS: Six patients with an average denervation time of 7.00 +/- 8.56
      years before surgery were followed for an average period of 16.3 +/- 2.42 years.
      All six eyes showed improvement of corneal sensibility, visual acuity, and
      corneal health and remained free of ulcers or other signs of advancing
      neurotropic keratopathy. Average corneal sensibility improved from 2.00 +/- 4.47
      mm before surgery to 278.00 +/- 226.00 mm following corneal neurotization (p <
      0.016). CONCLUSIONS: Direct neurotization of the cornea using the contralateral
      supraorbital and supratrochlear branches of the ophthalmic division of the
      trigeminal nerve appears to be an effective method of restoring the corneal
      sensibility in patients with unilateral facial palsy and anesthetic cornea. This
      technique preserves ocular anatomy and cosmesis and restores function by
      improving corneal health and visual acuity.

PMID- 19116545
TI  - The combination of muscle transpositions and static procedures for reconstruction
      in the paralyzed face of the patient with limited life expectancy or who is not a
      candidate for free muscle transfer.
AB  - BACKGROUND: In long-standing complete and irreversible facial palsy where
      reconstruction by nerve grafting alone is no longer sufficient, reconstruction by
      dynamic procedures such as muscle transplantation or muscle transposition is
      required. The authors present the results obtained by regional muscle
      transposition for reconstruction of eye closure and smile in patients with
      irreversible facial palsy. METHODS: Twenty-nine patients treated by temporalis
      transposition for the eye and eight patients treated by masseter transposition
      for the mouth are presented. Assessment of outcome was based on clinical
      examination and analysis of facial movements by three-dimensional video analysis.
      RESULTS: Preoperatively, the paretic eye fissure was on average 2.30 +/- 2.17 mm
      wider than the healthy one. The difference was reduced postoperatively to 0.95 +/
      1.89 mm. Paralytic lagophthalmus during closure of the eyes was 9.59 +/- 3.03 mm
      preoperatively and was reduced postoperatively to 4.33 +/- 2.68 mm. Ocular
      tearing and desiccation were reduced drastically in all patients. Static
      asymmetry of the mouth corner improved from 14.17 +/- 5.26 mm preoperatively to
      5.38 +/- 3.23 mm postoperatively. The index of dynamic symmetry improved from 
      0.17 +/- 0.25 preoperatively to 0.18 +/- 0.19 postoperatively. This means that,
      postoperatively, the amplitude of motion on the reconstructed side reached 18 +/-
      19 percent that of the amplitude on the healthy side, whereas preoperatively a
      shift of the paralyzed mouth corner toward the healthy side occurred.
      CONCLUSIONS: Muscle transposition improves static symmetry and provides dynamic
      activity to a certain degree. It is therefore a valuable concept for patients
      with limited life expectancy.

PMID- 19116546
TI  - Predictors of mortality after muscle flap advancement for deep sternal wound
      infections.
AB  - BACKGROUND: Deep sternal wound infection is a devastating complication following
      median sternotomy, with mortality rates reported from 1.0 to 36 percent. Several
      studies have evaluated the risk factors for the development of a deep sternal
      wound infection, but the factors predicting survival after debridement and muscle
      flap advancement are not well known. METHODS: A retrospective chart review was
      performed from September of 1997 to January of 2004 on all patients referred to a
      single plastic surgeon for treatment of a deep sternal wound infection following
      median sternotomy for cardiovascular surgery. The authors collected
      cardiovascular operative and intensive care unit data and information regarding
      patient demographics, medical history, laboratory studies, and follow-up. Data
      were analyzed as possible prognostic factors. RESULTS: During the collection
      period, a total of 8414 cardiovascular surgery cases were performed through a
      median sternotomy. Deep sternal wound infections were identified and treated with
      muscle flap advancement in 124 patients (1.5 percent). Most patients (90 percent)
      were treated with bilateral pectoralis major flap advancements. Eighty-five
      patients underwent debridement and muscle flap advancement as a single-stage
      procedure. There were 26 perioperative deaths (21 percent). Presternotomy end
      stage renal disease, presternotomy chronic obstructive pulmonary disease, and
      prolonged poststernotomy mechanical ventilation were found to be significant
      independent predictors of mortality despite muscle flap advancement. CONCLUSIONS:
      These data identify patients with deep sternal wound infections who may be at
      increased risk for mortality after debridement and muscle flap advancement. This
      information may help the patient, family, and surgeon modify medical management
      or surgical treatment of this devastating problem.

PMID- 19116547
TI  - 5-Fluorouracil treatment of problematic scars.
AB  - BACKGROUND: Keloids and hypertrophic scars can be uncomfortable, disfiguring, and
      aesthetically undesirable. Anecdotal reports suggest that low-dose intralesional
      fluorouracil can be used to treat these undesirable scars. METHODS: Using a
      prospective case series protocol, both keloid and hypertrophic scar patients were
      included. Keloid patients underwent excision followed by a series of treatments
      with intralesional 5-fluorouracil into the healing scar to prevent recurrence (n
      = 32). The hypertrophic scar patients were treated with the same series of
      injections without scar excision to both control symptoms and improve scar
      appearance (n = 21). The primary outcome measures were scar volume and a symptom
      questionnaire. Patients were followed for 1 year after completing the injection
      treatments. RESULTS: In the keloid group, the recurrence rate was 19 percent at 1
      year follow-up for this group of patients who had failed previous corticosteroid
      injection therapy. In the hypertrophic scar group, 14 percent did not respond to
      the series of injections. In this group, there was a median volume decrease of 50
      percent maintained for 1 year after injection therapy was terminated.
      CONCLUSIONS: Intralesional fluorouracil is a safe and effective means of
      controlling problem scars in terms of both recurrence and symptom control.
      Benefits were maintained for at least 1 year after completion of therapy.
      Intralesional 5-fluorouracil should be considered another option for patients
      suffering from problematic scars.

PMID- 19116549
TI  - Concept and anatomical basis of microdissected tailoring method for free flap
      transfer.
AB  - BACKGROUND: For a refined microsurgical reconstruction, it is desirable to adjust
      the flap to fit the three-dimensional details of the defect. Essentially, each
      vessel arborized in the subcutaneous adipose tissue supplies axial blood flow to
      an individual small area surrounding the vessel. Therefore, free alteration of
      the flap would be possible if the anatomy of these branches could be identified
      during surgery. METHODS: The microdissected tailoring method is a new procedure
      for alteration of the flap, observing the branches of the perforator directly
      after microdissection. By means of this procedure, three flaps were transferred
      to complex tissue defects. In addition, among intraadipose branches of 59
      perforators, 90 cases of three types of microdissected thin perforator flap
      transfer were measured to classify the anatomical variations relating to
      microdissected tailoring of the flap. RESULTS: All flap transfers were uneventful
      and no circulatory failure of the flaps was observed. Statistical analyses reveal
      that the intermuscular septum perforator branches at the deeper layer of the
      adipose tissue and then spreads more widely in the adipose layer than that of
      muscle perforator, regardless of the type of flap and the length of the
      intraadipose vessel. CONCLUSIONS: Microdissected tailoring of the flap provides
      the best solution for flap alteration in the reconstruction of a complex-shaped
      tissue defect. It represents a change in the concept of free flap transfer,
      because the flap is prepared according to the individual anatomy of the
      intraadipose vessel.

PMID- 19116550
TI  - Sensate thoracodorsal artery perforator flap: a focus on its preoperative design
      and harvesting technique.
AB  - BACKGROUND: Free sensate thoracodorsal artery perforator flaps that include the
      posterior divisions of the lateral cutaneous branches of the intercostal nerves
      have been described. The authors used preoperative color Doppler sonography to
      identify the nerves and demonstrate its clinical value. METHODS: Fourteen free
      sensate thoracodorsal artery perforator flaps were collected. Preoperative color
      Doppler sonography was used to identify the locations of thoracodorsal artery
      perforators and the courses of the posterior divisions of the lateral cutaneous
      branches of the intercostal neurovascular bundles. These posterior divisions were
      preserved on flaps and classified into three types. Type A and B nerves sprouted
      cutaneous perforating fascicles over the lateral region of the latissimus dorsi
      muscle. Type C nerves went through the region without any dominant perforating
      fascicle. RESULTS: Twenty-one nerves were mapped, and 24 were found during
      surgery. The sensitivity of preoperative color Doppler sonography was 87.5
      percent. Of the 24 nerves, nine were type A (37.5 percent), 12 were type B (50
      percent), and three were type C (12.5 percent). Ten of the 14 patients (sensate
      group) showed better tactile recovery at both the center and the periphery of
      flap than the other 10 patients who underwent reconstruction with nonsensate
      flaps. CONCLUSIONS: Preoperative color Doppler sonography is an indispensable
      tool for sensate thoracodorsal artery perforator flaps in locating the
      perforators and mapping the posterior divisions of the lateral cutaneous branches
      of the intercostal nerves. The information can be used to design and harvest
      sensate thoracodorsal artery perforator flaps, which are associated with earlier
      and better tactile recovery.

PMID- 19116551
TI  - Surgical outcomes of VRAM versus thigh flaps for immediate reconstruction of
      pelvic and perineal cancer resection defects.
AB  - BACKGROUND: Reconstruction following abdominoperineal resection or pelvic
      exenteration is commonly performed with regional flaps from the thigh or abdomen.
      This study compared the surgical outcomes and complications in cancer patients
      who underwent immediate reconstruction of these defects with vertical rectus
      abdominis myocutaneous (VRAM) versus thigh flaps. METHODS: One hundred thirty
      three patients who underwent abdominoperineal resection or pelvic exenteration
      for cancer resection and immediate VRAM (n = 114) or thigh flap (n = 19)
      reconstruction of the perineal/pelvic defect were studied. Patient, tumor, and
      treatment characteristics; surgical outcomes; and postoperative donor- and
      recipient-site complications were compared between the two groups. Multivariate
      logistic regression analysis was used to identify predictive/protective factors
      for complications. RESULTS: The thigh flap group had a significantly greater
      incidence of major complications (42 percent versus 15 percent) than the VRAM
      flap group. They also had significantly higher rates of donor-site cellulitis (26
      percent versus 6 percent) and recipient-site complications, including cellulitis
      (21 percent versus 4 percent), pelvic abscess (32 percent versus 6 percent), and
      major wound dehiscence (21 percent versus 5 percent). Abdominal wall
      complications were not increased in the VRAM group despite flap harvest from the
      abdominal wall. Obesity was an independent predictor of any donor-site
      complication (odds ratio, 3.3) and previous abdominal surgery was a predictor of
      any complication (odds ratio, 3.6), any recipient-site complication (odds ratio,
      3.5), and any major complication (odds ratio, 3.6). CONCLUSION: Immediate VRAM
      flaps result in fewer major complications than thigh flaps without increased
      early abdominal wall morbidity when used to repair abdominoperineal resection and
      pelvic exenteration defects.

PMID- 19116552
TI  - Marjolin's ulcer: modern analysis of an ancient problem.
AB  - BACKGROUND: Marjolin's ulcer is a rare but highly aggressive squamous cell cancer
      that is most often associated with chronic burn wounds. Although many individual
      case reports exist, no thorough evaluation of Marjolin's ulcer patients has been
      conducted to date. METHODS: The authors present their experience with 10 patients
      encountered over a period of 15 years and analyze 25 previous publications, for a
      total of 443 patients diagnosed with Marjolin's ulcer. RESULTS: Although burn
      scar represents 76.5 percent of patients in the authors' review, venous stasis
      ulcers, traumatic wounds, osteomyelitis, and pressure sores are also represented
      as wound types that can undergo malignant degeneration. CONCLUSIONS: The authors'
      review suggests that there is much variability in the anatomical location of
      Marjolin's ulcers, with the majority occurring in wounds of the upper and lower
      extremities. Marjolin's ulcer appears to be preventable if early wound coverage
      is undertaken. Countries with limited access to medical treatment report a high
      number of Marjolin's ulcers compared with more developed regions.

PMID- 19116553
TI  - Complex torso reconstruction with human acellular dermal matrix: long-term
      clinical follow-up.
AB  - SUMMARY: Although reports have demonstrated good early outcomes with human
      acellular dermal matrix even when used for complex, contaminated defects, no long
      term outcomes have been reported. The authors reviewed the long-term outcomes of
      13 patients who had complex torso reconstructions that included human acellular
      dermal matrix. All patients were at increased risk for mesh-related
      complications. Eight patients died as a result of progression of their oncologic
      disease at a mean of 258 days postoperatively. The mean follow-up for the
      remaining five patients was 43.7 months. Six patients had early complications
      (none were human acellular dermal matrix-related) and were reported on
      previously. Two patients had developed complications since the initial report.
      One patient developed a flap donor-site seroma remote from the reconstruction
      site, and another developed a recurrent ventral hernia. No patients have required
      additional surgery for human acellular dermal matrix-related complications. This
      follow-up report indicates that human acellular dermal matrix repair of large,
      complex torso defects can result in good long-term outcomes even when patients
      are at high risk for mesh-related complications.

PMID- 19116554
TI  - Partial joint denervation I: wrist, shoulder, and elbow.
AB  - BACKGROUND: Partial joint denervation is the concept of preservation of joint
      function and relief of joint pain by interrupting the neural pathways that
      transmit the pain message from the joint to the brain. When traditional,
      nonoperative, musculoskeletal approaches fail, the surgical approach may require
      joint fusion or replacement arthroplasty. The purpose of this article is to
      extend these concepts from the wrist to the elbow and shoulder. METHODS: For each
      joint, research required (1) anatomical dissection to identify innervation of the
      specific joint, (2) identification of route through which to administer local
      anesthetic based on new anatomical knowledge, (3) demonstration that pain relief
      is possible by injection of local anesthetic in patients who have failed
      traditional musculoskeletal treatments for that joint, (4) creation of surgical
      approach(es) to resect involved nerve(s), and (5) documentation of success of
      this approach with an appropriate patient population. RESULTS: The results
      obtained for partial joint denervation of the wrist can be applied successfully
      to the elbow and shoulder. If anesthetic block of joint innervation results in
      greater than or equal to a five-point reduction in visual analogue scale score,
      90 percent of the patients can expect good to excellent pain relief from partial
      joint denervation. CONCLUSIONS: Partial joint denervation offers an outpatient,
      ambulatory operative approach that is joint sparing and rehabilitation free. For
      plastic surgery, this concept opens new areas for patient care, permitting relief
      of pain and restoration of function to joints even proximal to the wrist,
      permitting plastic surgeons to bring this hope to our orthopedic and pain
      management colleagues.

PMID- 19116555
TI  - Partial joint denervation II: knee and ankle.
AB  - BACKGROUND: Partial joint denervation is the concept of preservation of joint
      function and relief of joint pain by interrupting neural pathways that transmit
      the pain message from the joint to the brain. Partial denervation of painful
      wrist, elbow, and shoulder joints was described in part I. Application of these
      principles to the knee and ankle is described in part II. METHODS: Cadaveric
      anatomical studies identified innervation of the knee and the ankle (sinus tarsi)
      to provide a guide to nerve blocks and surgical intervention. Patients were
      evaluated who had sports injuries, trauma, osteoarthritis, or previous
      arthroplasty/scope procedures of the knee and/or ankle who failed to respond to
      traditional musculoskeletal approaches. RESULTS: The results obtained for partial
      joint denervation of the upper extremity can be applied successfully to the knee
      and ankle joints. If anesthetic block of joint innervation results in a reduction
      of 5 or more the visual analogue scale, 90 percent of the patients can expect
      good to excellent pain relief from partial joint denervation. CONCLUSIONS: For
      patients with a structurally intact joint but with chronic knee or ankle pain
      after trauma or arthroplasty, this approach provides an outpatient, ambulatory
      operative approach that is joint sparing and can be rehabilitation-free. Partial
      joint denervation in the lower extremity offers plastic surgeons the opportunity
      to help our colleagues in orthopedic surgery, podiatric medicine, and pain
      management with some of their most difficult pain-related lower extremity patient
      problems.

PMID- 19116556
TI  - Lessons from operation Iraqi freedom: successful subacute reconstruction of
      complex lower extremity battle injuries.
AB  - BACKGROUND: War wounds associated with Operation Iraqi Freedom have created a
      unique reconstructive challenge. The objective of this study was to report and
      analyze the timing and success rates of lower extremity reconstruction associated
      with devastating war wounds. METHODS: A retrospective review was conducted of
      injured personnel requiring extremity flap reconstruction at the National Naval
      Medical Center over a 30-month period. Collected data included mechanism of
      injury, time from initial injury to closure, number of prereconstruction wound
      washouts, types of flap, flap failures, associated injuries, and wound culture
      characteristics. RESULTS: From September of 2004 to February of 2007, 46 (36
      pedicled and 10 free flaps) lower extremity flap reconstructions (10
      fasciocutaneous, 34 musculocutaneous, and two adipofascial) were performed on 43
      patients. Patient age ranged from 19 to 37 years. Time to reconstruction ranged
      from 7 to 82 days (average, 21 days). Seventy-six percent of all injuries were
      associated with an improvised explosive device blast. Mean number of
      prereconstructive washouts was five (range, two to 13). Fifty percent of all
      wounds cultured at admission revealed positive results, of which 57 percent were
      associated with Acinetobacter species. Total flap loss occurred in one flap and
      partial flap loss occurred in two flaps. CONCLUSION: Despite reconstruction in
      the subacute period, the high rate of antimicrobial colonization before wound
      closure, and the devastating nature of improvised explosive device blast
      injuries, early analysis of the National Naval Medical Center war extremity
      reconstruction cohort demonstrates low total and partial flap loss rates and
      acceptable infection rates.

PMID- 19116557
TI  - The use of supermicrosurgery in lower extremity reconstruction: the next step in
      evolution.
AB  - BACKGROUND: The purpose of this study was to evaluate the feasibility of
      supermicrosurgery (perforator-to-perforator anastomosis) in lower extremity
      reconstruction. METHODS: From January of 2007 to February of 2008, a total of 42
      patients were treated for soft-tissue defects of the lower extremity resulting
      from various causes. They were reconstructed with either anterolateral thigh
      perforator flaps (38 flaps) or upper medial thigh perforator flaps (four flaps)
      using the supermicrosurgery technique. The region of the defect was located on
      the knee, including the upper third of the leg in 17 patients and the middle
      third of the leg in 25 patients. All of the flaps were anastomosed between the
      perforators in end-to-end fashion. RESULTS: With the exception of one flap, all
      flaps survived without any complications. One flap was observed to have no flow
      after 24 hours and was deemed unsalvageable. The average time of operation was 3
      hours 20 minutes. Ambulation was allowed within 7 days after surgery if bone
      status was feasible. CONCLUSIONS: The use of supermicrosurgery in lower extremity
      reconstruction allows an increase in selection of recipient pedicles. By using a
      perforator-to-perforator anastomosis approach, less time is consumed in securing
      the recipient vessel and elevating the flap, and the risk for major vessel injury
      is minimized and flap survival is acceptable. However, it requires a steep
      learning curve before the technique can be used comfortably. The
      supermicrosurgery technique is feasible and may be efficient in the hands of a
      skilled surgeon.

PMID- 19116558
TI  - The angiosomes of the thigh and buttock.
AB  - BACKGROUND: The angiosomes of the body were defined in 1987. The recent
      popularity of skin perforator and muscle flaps designed in the thigh, together
      with significant major vessel anomaly and disease, has necessitated a more
      detailed reevaluation of the blood supply to this region. METHODS: Eighteen new
      studies, combined with a review of 36 of the authors' archival studies of the
      buttock and the thigh, have been conducted in fresh human cadavers using arterial
      perfusion with a radiographic lead oxide mixture. RESULTS: The angiosome
      territories of the lumbar, deep circumflex iliac, sacral, gluteal, common
      femoral, superficial femoral, lateral femoral circumflex, medial femoral
      circumflex, profunda, descending genicular, and popliteal source vessels that
      contribute to the thigh and buttock were defined between the skin and the bone.
      The dominant cutaneous supply of perforators of 0.5 mm or greater emerged from
      the deep fascia predominantly in longitudinal rows from the intermuscular septa
      or from intramuscular septa, especially from the buttock muscles. Each muscle was
      supplied from two or more angiosomes, thereby constituting important bypass
      shunts for potential major vessel injury or disease, by means of their
      intramuscular anastomoses. CONCLUSIONS: These results may help the surgeon in the
      design of skin perforator and refined muscle, musculocutaneous, and composite
      flaps in the thigh and the buttock. The study also provides for a better
      understanding of vessel anastomoses in the region.

PMID- 19116559
TI  - The pedicled gastrocnemius muscle flap: a review of 218 cases.
AB  - BACKGROUND: Data regarding donor-site morbidity, postoperative clinical course,
      and functional and aesthetic outcome after gastrocnemius muscle flaps are rare.
      METHODS: Data regarding 218 consecutive patients treated with gastrocnemius
      muscle flaps were acquired from patients' charts and from contact with patients,
      with special reference to treatment and clinical course. Eighty-two were
      interviewed with a standardized questionnaire, 40 were examined physically, and
      34 underwent dynamometric muscle function tests. RESULTS: The authors observed
      wound-healing difficulties in 7 percent, wound infections in 4 percent, and one
      flap loss; 4.5 percent of the lateral gastrocnemius patients suffered from
      postoperative palsy of the peroneal nerve. Eighty-seven percent were not
      significantly limited walking on even ground, but only 42 percent could run, and
      40 percent complained about pain when walking more than 200 m. The average range
      of-motion deficit in the ankle joint for flexion and extension was 11 percent and
      10 percent, respectively. The maximal plantar flexion force in the ankle joint of
      the operated leg was 76.2 percent. Strength endurance was reduced approximately
      24.4 percent in the operated leg compared with the nonaffected side. CONCLUSIONS:
      Gastrocnemius muscle transfer represents a safe and simple procedure in the
      treatment of lower leg defects and in limb preservation. The strength loss and
      functional impairment (and sensation disorders) are considerable but may not be
      exclusively attributable to the muscle transfer but rather the result of the
      preceding trauma, infection, or tumor resection. The donor-site morbidity is well
      tolerated by the majority of the patients.

PMID- 19116560
TI  - Immediate reconstruction of a nonreplantable thumb amputation by great toe
      transfer.
AB  - BACKGROUND: When replantation of an avulsed/amputated thumb is not feasible, toe
      to-hand transfer may be considered as a reconstructive option in appropriately
      chosen patients. Although selection criteria are purposefully restrictive,
      immediate one-stage transfer, as opposed to a delayed procedure, provides many
      advantages. Primary reconstruction reduces hospitalization and operative and
      recovery time. It also may expedite return of function and allow patients to
      return to work sooner. The ability of the patient to undergo extensive
      microvascular reconstruction at the time of injury, the psychological preparation
      required, and the need to understand potential risks are important factors to
      consider. METHODS: In the past 5 years, six patients suffering thumb amputation
      underwent immediate great toe-to-hand transfer. The overall results of these
      thumb reconstructions were evaluated retrospectively with regard to function,
      outcome, length of stay, complications (e.g., infection, contracture,
      reexploration), and time to return to work/normal activity. The authors
      calculated objective and subjective scores with which to quantify patient
      satisfaction and clinical success. RESULTS: All of the authors' patients were
      laborers who suffered work-related avulsion-amputations. No complications were
      reported during initial hospitalization, lasting an average of 12 days. Donor
      site morbidity was minimal. CONCLUSIONS: The data suggest that thumb
      reconstruction using great toe transfer can be safely and reliably performed
      during the initial presentation in selected patients. The economic and
      therapeutic advantages should be weighed against the risks associated with this
      approach when evaluating thumb avulsion-amputations.

PMID- 19116561
TI  - Triple chimeric flap based on anterior tibial vessels for reconstruction of
      severe traumatic injuries of the hand with thumb loss.
AB  - BACKGROUND: Reconstruction of severe traumatic injuries of the hand with digit
      loss may require multiple procedures over a prolonged period. The authors present
      a clinical series of patients in which these types of injuries were reconstructed
      in a single operation. METHODS: A chimeric flap based on the anterior tibial
      vessels is described. A total of three free tissue transfers included an anterior
      tibial flap, a dorsalis pedis flap, and a great toe wrap-around flap. These
      triple flaps were transferred to resurface the defects of the mutilated hand,
      which was involved in the thumb, first web space, volar palm, thenar eminence, or
      radial aspect of wrist. The cumulative size of the defects ranged from 9 x 11 cm
      to 12 x 18 cm. RESULTS: From 2002 to 2007, six patients with multiple defects of
      the hand and thumb underwent reconstruction using the described technique. The
      donor sites were covered by means of split-thickness skin grafting. All flaps
      survived and patients were satisfied with the functional and aesthetic outcome
      postoperatively at 6 to 12 months' follow-up. The average improvement of thumb
      opposition was 4.8 on the Kapandji scale. Sensory recovery of the thumb tip of S3
      was achieved. There were no major donor-site complications. CONCLUSION: A
      chimeric flap based on the anterior tibial vessels is an excellent method of
      reconstruction of severe multilevel injuries of the hand, including thumb loss.

PMID- 19116562
TI  - Sensory recovery of the hand with intercostal nerve transfer following complete
      avulsion of the brachial plexus.
AB  - BACKGROUND: Restoration of sensory function is imperative when prehensile
      function is restored after irreparable brachial plexus injury. However, there are
      few reports that focus on the results of sensory recovery after brachial plexus
      reconstruction. The purpose of this article is to report the results of sensory
      recovery of the hand with intercostal nerve transfer following complete brachial
      plexus injury. METHODS: Seventeen patients with complete brachial plexus injury
      underwent sensory reconstruction of the hand with intercostal nerve transfer to
      the median or ulnar nerve. All patients underwent double free-muscle transfer to
      restore the prehensile function of the hand. Sensory recovery of the hand was
      assessed with Semmes-Weinstein monofilament testing, two-point discrimination,
      vibration perception, temperature perception, and the location of perception of
      sensibility. The average follow-up period was 4.1 years. RESULTS: All patients
      perceived at least the 6.65 filament at the territory of the median or ulnar
      nerve. Best result on Semmes-Weinstein monofilament test was perception of the
      4.31 filament in two patients. None of the patients had two-point discrimination.
      Vibration with 30-cycles/second stimuli was perceived in 12 patients, whereas
      vibration with 256-cycles/second stimuli was perceived in only six patients.
      Eight patients had perception of warmth, and 13 patients had perception of cold.
      Seven patients felt sensation in the cutaneous distribution of the repaired nerve
      of the hand in situ. CONCLUSIONS: Sensory reconstruction with intercostal nerve
      transfer can provide limited sensibility of the hand. However, this limited
      sensory recovery is useful for activities of daily living in severely handicapped
      patients with brachial plexus injury.

PMID- 19116563
TI  - Split-thickness skin flap technique for elevating the radial forearm flap.

PMID- 19116564
TI  - Symptom outcomes following cranial vault expansion for craniosynostosis in
      children older than 2 years.
AB  - BACKGROUND: Most craniosynostosis cases are treated by cranial expansion before 1
      year of age. Occasionally, patients present at a later age with nonspecific
      symptoms of increased intracranial pressure. The purpose of this study was to
      review the symptoms of patients undergoing late cranial vault expansion. In all
      cases, the indication for surgery was treatment of the cranial dysmorphology.
      METHODS: The authors performed a retrospective review of all patients (n = 17)
      undergoing cranial vault expansion from 2000 to 2007 aged older than 2 years
      (median, 7.4 years) for abnormal head shape who also reported preoperative
      symptoms consistent with increased intracranial pressure, including headaches,
      nausea or vomiting, or vision changes. Median follow-up was 30 months; 11
      patients had nonsyndromic and six had syndromic craniosynostosis. RESULTS:
      Fourteen patients had headaches, nine had nausea and vomiting, and 11 had vision
      changes. Ten patients had signs of intracranial pressure elevation, such as a
      computed tomographic scan findings, papilledema, or both. Twelve of 14 patients
      had complete resolution of headaches following surgery and four had late mild
      recurrence. All patients with nausea and vomiting and nine of 11 patients with
      vision changes had resolution of symptoms. CONCLUSIONS: The diagnosis of
      increased intracranial pressure in older children with craniosynostosis is
      difficult in the absence of papilledema or computed tomographic findings.
      Clinical symptoms frequently associated with increased intracranial pressure are
      improved with late cranial vault expansion and demonstrate a possible benefit
      beyond improvement in head shape.

PMID- 19116566
TI  - Comparison of computed tomographic imaging measurements with clinical findings in
      children with unilateral lambdoid synostosis.
AB  - BACKGROUND: In this study, the authors retrospectively reviewed 12 children with
      unilateral lambdoid synostosis to compare and contrast clinical findings and
      associated computed tomographic scan measurements for consistency. METHODS:
      Multidisciplinary chart records were reviewed for descriptive findings of
      unilateral lambdoid synostosis. The preoperative computed tomographic scans
      underwent quantitative analysis of craniofacial morphology. The described
      clinical findings were compared with the associated computed tomographic
      measurements for consistency. RESULTS: Clinical findings of unilateral lambdoid
      synostosis that were consistent with computed tomographic measurements included
      mastoid cant and bulge, and inferior ear position. Ipsilateral posterior ear
      position was clinically noted in half of the cases but was anterior in all cases
      on computed tomographic analysis. Trapezoid head shape was recorded in 11 of the
      12 children but present in only eight computed tomographic scans. Median skull
      base deviation was 9 degrees for the posterior cranial fossa, 10 degrees for the
      middle cranial fossa, 6 degrees for mastoid cant, and 1 degree for facial twist.
      There was no correlation between degree of deformity and extent of suture fusion.
      CONCLUSIONS: Mastoid bossing, skull base cant, and inferior ear deviation
      ipsilateral to the fused sutures were clinical findings that were consistent with
      computed tomographic measurements in these patients. Trapezoid head shape and
      posterior ear deviation were not. Radiographic suture fusion was observed in all
      cases; however, the extent of fusion did not correlate with the degree of
      deformity.

PMID- 19116567
TI  - Three tenets for staged correction of Kleeblattschadel or cloverleaf skull
      deformity.
AB  - BACKGROUND: Patients with cloverleaf skull deformity are known to have high
      morbidity and poor outcome. Physical anomalies include a misshapen, trilobar
      skull, with a high "bossed" forehead, a bulging temporal region, and a flat
      posterior skull from multiple cranial suture fusion. METHODS: Patients with
      cloverleaf skull deformity treated at the University of California, Los Angeles
      from 1990 to 2006 (n = 14) underwent early cranial vault remodeling (group 1) or
      staged correction with ventriculoperitoneal shunt (neonate), fronto-orbital
      advancement (3 to 6 months), and posterior vault remodeling (1 year) (group 2).
      Morbidity, necessary revisions, and neurologic (developmental testing) and
      aesthetic (Whitaker score) outcomes were assessed at follow-up. RESULTS:
      Diagnoses included Apert syndrome, Crouzon syndrome, Pfeiffer syndrome, Saethre
      Chotzen syndrome, and nonsyndromic. Early cranial vault remodeling patients had
      more complications than staged correction patients [pneumonia, meningitis, and
      excessive bleeding (each 66 percent versus 9 percent); wound infection (66
      percent versus 18 percent); and seizure (100 percent versus 0 percent)]. Early
      cranial vault remodeling patients had prolonged intensive care unit and hospital
      stays compared with staged correction patients (13 versus 2 days and 27 versus 5
      days, respectively). The Whitaker score showed acceptable results at 18 months in
      group 2 (1.4, no revisions necessary) but not in group 1 (2.8, minor to major
      bony recontouring). Developmental tests showed that all early cranial vault
      remodeling patients had lower scores in both preschool tests and global
      evaluations compared with normative data (mean preschool receptive scores, 95
      versus 85; mean preschool expressive scores, 94 versus 87). CONCLUSION: Staged
      correction of cloverleaf skull provided acceptable neurologic and aesthetic
      outcomes in the authors' series of patients.

PMID- 19116568
TI  - Application-specific selection of biomaterials for pediatric craniofacial
      reconstruction: developing a rational approach to guide clinical use.
AB  - BACKGROUND: Biomaterials provide an invaluable alternative to autogenous bone
      graft for pediatric craniofacial reconstruction. However, there is no uniform
      agreement on the choice of biomaterial for different reconstructive needs.
      METHODS: Patients who had reconstruction of the craniofacial skeleton with
      alloplastic materials from 1994 to 2006 by a single surgeon were reviewed.
      Biomaterials used consisted of three classes: cement pastes, biomaterials
      designed to be replaced by bone, and prefabricated polymers. The study included
      25 patients with a mean age of 5.5 years and a mean follow-up of 3.3 years.
      RESULTS: Cement pastes used for onlay augmentation to the cranial skeleton in
      eight patients consisted of hydroxyapatite (n = 5) and calcium phosphate (n = 3).
      One patient had a postoperative infection that resolved with partial implant
      removal and antibiotics. Biomaterials designed to be replaced by bone consisted
      of bioactive glass (n = 3) and demineralized bone (n = 8), which were used for
      inlay reconstruction of full-thickness calvarial defects in 11 patients. Computed
      tomographic scanning showed adequate bone mineralization in nine patients; two of
      the three patients with calvarial defects greater than 5 cm in diameter
      demonstrated variable mineralization. Prefabricated porous polyethylene was used
      in six patients for either onlay malar augmentation (n = 3) or inlay calvarial
      reconstruction (n = 3). One patient had a peri-implant infection that resolved
      with aspiration, irrigation, and intravenous antibiotics. CONCLUSIONS: The
      authors developed an algorithm to guide use of biomaterials in craniofacial
      reconstruction based on whether (1) growth of the underlying craniofacial
      skeleton is nearly complete (>90 percent); (2) onlay or inlay reconstruction is
      to be performed; and (3) the reconstruction is performed in a load-bearing or non
      load-bearing area.

PMID- 19116570
TI  - External distraction osteogenesis in the pediatric mandible.
AB  - SUMMARY: Mandibular distraction osteogenesis is an effective tool with which to
      correct facial asymmetry, restore proper occlusion and, more importantly, create
      an appropriate airway in the micrognathic infant. As a component of many
      syndromes, micrognathia can impair feeding and speech development and can
      obstruct the neonatal airway. However, bony lengthening secondary to external
      mandibular distraction osteogenesis can provide added space, preventing
      oropharyngeal soft tissues from occluding the airway. Although external
      distraction of the mandible has been applied for more than a decade, this
      procedure often proves technically challenging. Here, as a supplement to their
      video presentation, the authors present a practical discussion of their current
      technique for mandibular distraction osteogenesis using an external device in a
      child with Treacher Collins syndrome.

PMID- 19116569
TI  - Microsurgical salvage of the intractable oral vestibule.
AB  - BACKGROUND: The significance of the oral vestibule is often underappreciated in
      composite craniomaxillofacial reconstruction, and its deficiency results in
      considerable incompetence. Results of traditional vestibuloplasty techniques are
      unpredictable when the recipient bed is compromised in the setting of trauma or
      irradiation. The authors present an alternative approach for restoring the
      intractable oral vestibule with free tissue transfer. METHODS: An institutional
      review board-approved retrospective review of patients who underwent oral
      vestibular reconstruction was conducted at R Adams Cowley Shock Trauma Center and
      Johns Hopkins Hospital from 2002 to 2007. RESULTS: Thirteen patients were
      identified: six defects resulted from tumor extirpation, six resulted from
      traumatic injury, and one resulted from infection. There were eight men and five
      women, with a mean age of 46 years. Thirteen free tissue transfers of the oral
      vestibule were conducted: six ulnar forearm and seven anterolateral thigh
      perforator flaps. The average follow-up was 17 months. There were no flap
      failures and only one complication noted, which did not result in negative
      sequelae. The functional results were good, with all patients experiencing
      increased labial excursion and subjective improvement in the handling of food
      bolus and saliva. CONCLUSIONS: Preservation of oral vestibular height, width, and
      volume is essential for aesthetic appearance and functional competence. Free
      tissue transfer provides an innovative alternative in the management of the
      intractable and obliterated oral vestibule. It can be performed successfully,
      providing excellent results predictably.

PMID- 19116571
TI  - Nasal tip surgery using a modified septal extension graft by means of extended
      marginal incision.
AB  - BACKGROUND: The columellar strut is considered one of the standard procedures in
      nasal tip surgery, as it provides a structural foundation for the nasal tip.
      Although effective for most Caucasians, the columellar strut often results in a
      suboptimal outcome and does not provide an adequate foundation in Asian tip
      surgery. For an optimal outcome, the authors propose a different surgical
      paradigm for Asian tip surgery. METHODS: Using an extended marginal incision, a
      wide-field endonasal dissection is performed and the distal nasal framework
      including the alar cartilages and the caudal septum is exposed widely. A septal
      extension graft is made from a preoperatively designed paper template, with
      markings for anchoring the alar cartilage and overlapping with the caudal septum.
      The extension graft is fixed to the caudal septum and the alar cartilages are
      sutured to the extension graft at the precise position using markings transferred
      to the extension graft. RESULTS: This procedure was applied in 217 Asian
      rhinoplasties, with all patients having substantial improvement in their nasal
      tip shape. The advantages of this technique are numerous and include stable tip
      support and versatility in nasal tip modification. The same basic techniques and
      sequence can be applied to correct a wide range of tip deformities found in Asian
      noses. CONCLUSIONS: The authors' surgical paradigm combining the modified septal
      extension graft with wide-field endonasal dissections provides a unique
      opportunity to gain greater control and a more predictable outcome in Asian tip
      surgery. Stable septal support is crucial to the success of this technique.

PMID- 19116572
TI  - Preventing and managing dry eyes after periorbital surgery: a retrospective
      review.
AB  - BACKGROUND: Dry eye syndrome is a common sequela associated with periorbital
      surgery. As more patients seek periorbital rejuvenation, understanding the
      pathophysiology, diagnosis, and treatment of this condition perioperatively is
      essential for managing patient expectations and maximizing outcomes. METHODS: A
      retrospective review of charts for 202 consecutive patients (180 women and 22
      men) who underwent upper and/or lower blepharoplasty was performed. Additional
      facial cosmetic procedures were performed in 91 percent of patients. Data were
      collected identifying associated risk factors and the incidence of persistent dry
      eye symptoms. Key elements of perioperative care are described and algorithms for
      detection of those at risk, prevention, and management are outlined. RESULTS: Dry
      eyes persisting longer than 2 weeks after surgery were noted in 22 patients (10.9
      percent) and longer than 2 months in only four patients (2 percent). In most
      cases, dry eyes resolved with conservative management, including artificial
      tears, lubrication, topical and systemic steroids, and night taping. One patient
      (0.5 percent of all studied patients) eventually needed surgical correction of
      lower eyelid retraction after failure of the punctate plug. Persistent chemosis
      occurred in 15 patients (68.2 percent) who had symptomatic dry eyes (p < 0.01).
      CONCLUSION: Recognizing and addressing risk factors before surgery and an
      algorithmic approach to prevention and management of patients undergoing
      periorbital surgery are essential for minimizing the occurrence of dry eye
      syndrome.

PMID- 19116573
TI  - Complications after autologous fat injection to the breast.
AB  - BACKGROUND: Although autologous fat injection (fat grafting) to the breast was
      performed widely throughout the twentieth century, the authors at their hospital
      have recently had to repair the damage suffered by a number of patients subjected
      to this procedure. The authors are concerned that this procedure is being
      performed incorrectly by untrained and untutored individuals, especially in
      Japan. The authors report several cases of complications after this procedure.
      Several related issues are discussed. METHODS: The authors retrospectively
      reviewed 12 patients who had received autologous fat grafts to the breast and
      required breast surgery and/or reconstruction to repair the damage presenting
      between 2001 and 2007. The symptoms are described and the fat grafting procedures
      that were used are analyzed. RESULTS: All 12 patients (mean age, 39.3 years) had
      received fat injections to the breast for augmentation mammaplasty for cosmetic
      purposes. They presented with palpable indurations, three with pain, one with
      infection, one with abnormal breast discharge, and one with lymphadenopathy. Four
      cases had abnormalities on breast cancer screening. All patients underwent
      mammography, computed tomography, and magnetic resonance imaging to evaluate the
      injected fats. CONCLUSIONS: Autologous fat grafting to the breast is not a simple
      procedure and should be performed by well-trained and skilled surgeons. Patients
      should be informed that it is associated with a risk of calcification, multiple
      cyst formation, and indurations, and that breast cancer screens will always
      detect abnormalities. Patients should also be followed up over the long-term and
      imaging analyses (e.g., mammography, echography, computed tomography, and
      magnetic resonance imaging) should be performed.

PMID- 19116575
TI  - Implications of weight loss method in body contouring outcomes.
AB  - BACKGROUND: Patients frequently present for body contouring after massive weight
      loss resulting from bariatric procedures or diet and exercise. The authors
      investigated whether body contouring complications vary by weight loss method.
      METHODS: Four hundred forty-nine patients (511 cases) were entered into a
      prospective registry. Diet and exercise patients were matched to bariatric
      patients based on identical procedures performed. Conditional logistic regression
      was used to test for differences between groups. One-to-one matching was then
      performed by nearest neighbor matching to the most similar patient who underwent
      bariatric procedures based on sex, age, and body mass index. The t test was used
      to compare matched patients. RESULTS: Twenty-nine patients (6.5 percent) lost
      weight exclusively through diet and exercise. They had significantly higher
      preoperative hematocrit (p = 0.02) and hemoglobin (p = 0.05), and tended to have
      multiple procedures performed at the same time, higher absolute complication
      rates, and significantly higher infection rates (p = 0.03). When matched to 191
      bariatric patients based on procedures performed, diet and exercise patients had
      a higher complication rate that did not reach significance (odds ratio, 1.5; p =
      0.28). One-to-one matching resulted in 34 procedure-matched pairs with
      nonsignificant trends toward better nutrition and more complications in diet and
      exercise patients. CONCLUSIONS: Infection rates were higher in patients who had
      body contouring after massive weight loss from diet and exercise versus bariatric
      procedures. When matched, despite lower nutrition markers, patients treated with
      bariatric procedures had outcomes similar to those of diet and exercise patients.
      We did not find evidence for an association between weight loss method and risk
      in the body contouring patient.

PMID- 19116576
TI  - Perioperative management of antidepressants and herbal medications in elective
      plastic surgery.
AB  - BACKGROUND: Patients seeking elective aesthetic surgery often use herbal
      medications and/or antidepressants. As the popularity of these medications grows,
      the plastic surgeon must become familiar with these drugs and their potentially
      harmful effects during the perioperative period. METHODS: The authors performed a
      PubMed search to identify commonly used herbs and antidepressants and their
      effects on patients during elective cosmetic surgery. RESULTS: Case series,
      studies, and reviews for 29 of the most common herbs and antidepressant
      medications were obtained from this search. On the basis of the existing data,
      the authors established recommendations for the management of these medications
      before elective cosmetic surgery. CONCLUSIONS: Most commonly used herbs and
      antidepressant medications have potentially deleterious effects on the patient
      during surgery, ranging from increased risk of bleeding to fatal interactions.
      The plastic surgeon must be familiar with these drugs to manage these patients
      appropriately.

PMID- 19116578
TI  - The error of omission: a simple checklist approach for improving operating room
      safety.
AB  - SUMMARY: The primary goal of patient safety must go hand in hand with the goal of
      producing reliably good aesthetic and functional results. The implementation of a
      proactive checklist improves operating room communication and takes the necessary
      step toward reducing the often neglected errors of omission. These steps are
      necessary if we are to ultimately achieve our goal of improving safety
      comprehensively in the operating room.

PMID- 19116577
TI  - Evidence-based medicine: the fourth revolution in American medicine?
AB  - SUMMARY: The use of evidence has become a force in American medicine to improve
      the quality of health care. Funding decisions from payers will demand studies
      with high-level evidence to support many of the costly interventions in medicine.
      Plastic surgery is certainly not immune to this national tidal wave to revamp the
      health care system by embracing evidence-based medicine in our practices. In
      scientific contributions of plastic surgery research, application of evidence
      based principles should enhance the care of all patients by relying on science
      rather than opinions. In this article, the genesis of evidence-based medicine is
      discussed to guide plastic surgery in this new revolution in American medicine.

PMID- 19116579
TI  - Reducing U.S. health care spending: is it realistic or even desirable?
AB  - BACKGROUND: Many people believe that U.S. health care spending (16.3 percent of
      gross domestic product) and especially the health care spending growth rate (6.7
      percent) are unsustainable by our economy and must be reduced. Its tremendous
      cost, along with indisputable quality and other problems, has led to the judgment
      that our health care system is in crisis. Performance improvement initiatives and
      public policy changes, it is hoped, will result in a "high-performance" health
      care system that simultaneously improves quality and reduces cost. The
      assumptions (1) that it is necessary and desirable to reduce U.S. health care
      spending and (2) that current performance improvement initiatives or politically
      and socially acceptable alternatives can successfully reduce expenditures are
      explored. METHODS: Current relevant health care economics and health care policy
      literature and position articles were reviewed. RESULTS: Initiatives to improve
      health care quality, access, efficiency, and efficacy are needed. Although health
      care expenditure reductions may be achieved by optimizing performance,
      significant and sustainable reductions in aggregate health care spending and
      spending growth rate are unlikely and may not be desirable. CONCLUSIONS: The
      economic and societal benefits associated with health care spending are
      underappreciated and must be recognized. Politicians, business leaders, and
      taxpayers should accept the reality that even if an efficient high-performance
      health care system is actually achieved in the United States, a major reduction
      in spending growth is unlikely unless Americans accept currently unacceptable
      restrictions and limitations in access to technology and services.

PMID- 19116580
TI  - The disruptive physician: righteous Maverick or dangerous Pariah?
AB  - BACKGROUND: "Disruptive physician" is a term appearing more frequently in many
      hospital bylaws. It has significant negative implications that can lead to loss
      of privileges for plastic surgeons. METHODS: Exploring the various definitions of
      disruptive physician reveals palpable differences between those of the Joint
      Commission and the American Medical Association. These discrepancies expose
      plastic surgeons to potential harm when actively addressing quality issues in the
      hospital environment. RESULTS: The disruptive label can be inappropriately
      leveraged by hospital administrators against plastic surgeons who confront
      quality issues. Moreover, the term disruptive is open to subjective
      interpretation. Challenging the disruptive label in court reveals only that the
      justice system is concerned that the actual process leading to the disruptive
      charge is followed appropriately as outlined within the organizational bylaws;
      the courts are not interested in the actual quality issues and generally will not
      second-guess the judgment of peer review panels or hospital administrators.
      CONCLUSIONS: Plastic surgeons would benefit from familiarizing themselves with
      these issues. Hospitals should be required to use root cause analysis when
      dealing with quality issues raised by members of the medical staff. Furthermore,
      findings from root cause analysis should be privileged from legal discovery in
      all jurisdictions to permit honest exploration of quality issues. When a conflict
      does arise, consideration of mediation should be given to resolve disputes.

PMID- 19116581
TI  - The personality factor in medical liability.

PMID- 19116584
TI  - Topical lineage-negative progenitor-cell therapy for diabetic wounds (invited
      discussion).

PMID- 19116585
TI  - Success of the orbicularis oculi myocutaneous vertical v-y advancement flap for
      upper eyelid reconstruction.

PMID- 19116586
TI  - Treatment of recurrent earlobe keloids with surgery and high-dose-rate
      brachytherapy.

PMID- 19116588
TI  - Our technique of "tongue" folding.

PMID- 19116590
TI  - Upper lip augmentation: palmaris longus as an autologous filler.

PMID- 19116592
TI  - A problem of power.

PMID- 19116593
TI  - The reconstruction of Venus: following our legacy.

PMID- 19116594
TI  - The reconstruction of Venus: following our legacy.

PMID- 19116595
TI  - Mandating departments of plastic surgery: the future of plastic surgery is now.

PMID- 19116596
TI  - The reconstruction of Venus: following our legacy.

PMID- 19116598
TI  - Operating room fires.

PMID- 19116599
TI  - Peripheral neuropathy in an adolescent treated with linezolid.
AB  - The increased incidence of methicillin-resistant Staphyloccocus aureus infections
      may increase linezolid use in children. Peripheral neuropathy is a rare adverse
      effect of linezolid therapy and is more frequent with prolonged courses. We
      present an adolescent with peripheral neuropathy after 4 months of linezolid
      therapy and review the literature related to linezolid-induced neuropathies.
      Children receiving long-term linezolid therapy should be monitored for
      neuropathy.

PMID- 19116600
TI  - Ciprofloxacin 0.3%/dexamethasone 0.1% sterile otic suspension for the topical
      treatment of ear infections: a review of the literature.
AB  - The objective of this article is to review the literature related to
      ciprofloxacin 0.3% and dexamethasone 0.1% sterile otic suspension. A systematic
      literature search utilizing Medline was conducted to identify peer-reviewed
      articles related to safety and efficacy. A total of 47 publications were
      identified and reviewed herein. The literature supports the use of
      antibiotic/antiiflammatory combination ear drops in the treatment of both acute
      otitis externa and acute otitis media in pediatric patients with tympanostomy
      tubes. Ciprofloxacin/dexamethasone has been demonstrated as safe and effective
      with regard to clinical cures and microbiological eradication of pathogens in
      either disease with low treatment failure rates. Additionally, the literature
      also provides clear evidence for the contribution of dexamethasone when added to
      ciprofloxacin for the topical treatment of ear infections.

PMID- 19116601
TI  - Intravenous colistimethate (colistin) use in critically ill children without
      cystic fibrosis.
AB  - INTRODUCTION: The increasing frequency of infections caused by multidrug
      resistant (MDR) Gram-negative bacteria has led to the reappraisal of
      colistimethate use. METHODS: We present a case series of critically ill pediatric
      patients without cystic fibrosis who received intravenous colistimethate
      treatment. All available relevant medical records were reviewed. RESULTS: Seven
      children without cystic fibrosis (mean age 7.7 years; 2 female), admitted to the
      intensive care unit of a tertiary-care pediatric hospital in Athens, Greece, were
      identified to have received intravenous colistimethate during October 2004 to May
      2008. MDR Acinetobacter baumannii, Pseudomonas aeruginosa, and/or Klebsiella
      pneumoniae were isolated from blood and/or bronchial secretions specimens in 6 of
      7 reported patients. All isolates were susceptible to colistin. All 7 patients
      received intravenous colistimethate in a dosage of 5 mg/kg daily (divided in 3
      equal doses, administered every 8 hours). Five children received colistimethate
      for 10 days and the remaining 2 for 2 and 23 days, respectively. The infections
      caused by MDR Gram-negative bacteria were improved in 6 children with
      microbiologically documented infections. Five of the 7 children were discharged
      from the ICU. The remaining 2 children died (1 of them had received
      colistimethate for 2 days); their death was not attributed to MDR Gram-negative
      infection. No nephrotoxicity or other type of toxicity of colistimethate was
      noted in this case-series. CONCLUSIONS: Although the small number of included
      cases precludes any firm conclusions, our study suggests that colistimethate may
      have a role for the treatment of infections caused by MDR Gram-negative bacteria
      in critically ill pediatric patients.

PMID- 19116602
TI  - Infection by Helicobacter pylori in Bangladeshi children from birth to two years:
      relation to blood group, nutritional status, and seasonality.
AB  - BACKGROUND: A birth cohort of 238 children was followed in an urban slum in
      Dhaka, Bangladesh, to determine incidence, prevalence, and epidemiologic factors
      related to Helicobacter pylori infection. METHODS: H. pylori infection was
      determined by a specific stool antigen test as well as enzyme-linked
      immunosorbent assay for detecting specific IgA and IgG antibodies in sera in
      children who completed 2 years of follow-up. RESULTS: Using the stool antigen
      test and serology, 50% and 60% of infants respectively, were positive for H.
      pylori by 2 years; an increase in the infection rate was seen after 6 months of
      age. Determination of specific antibodies in sera and detection of H. pylori
      antigen in stool were comparable. A typical seasonality, peaking in spring and
      autumn, was observed for acquisition of initial H. pylori infection. Children
      with blood group "A" were more susceptible to H. pylori infection than those with
      other ABO blood groups. Malnutrition did not seem to promote colonization by H.
      pylori. However, H. pylori-infected children were more often infected by multiple
      enteropathogens, often isolated at different time points. CONCLUSIONS: This study
      shows that noninvasive diagnostic methods such as serology and the stool antigen
      test are suitable for the study of acquisition of H. pylori infections in infants
      and can be used in field settings as well as in laboratories and clinical setting
      having less well equipped facilities. The study also shows seasonality for
      initial H. pylori infection and a relationship between blood group "A" and
      infection.

PMID- 19116603
TI  - A randomized trial to determine the tolerability and immunogenicity of a
      quadrivalent meningococcal glycoconjugate vaccine in healthy adolescents.
AB  - BACKGROUND: Because of the well-documented increased risk of meningococcal
      disease among adolescents, vaccination is recommended for this population in many
      countries, including the United States. This study compared the tolerability and
      immunogenicity in adolescents of a candidate quadrivalent meningococcal CRM197
      glycoconjugate vaccine against serogroups A, C, W-135, and Y (MenACWY-CRM) with
      that of the licensed unconjugated quadrivalent polysaccharide vaccine (MPSV4).
      METHODS: This phase II study was conducted in the United States among 524
      adolescents aged 11-17 years in 2 stages, with different randomization schemes.
      The first 334 participants, enrolled in Stage 1, were randomized (1:1) to receive
      either MenACWY-CRM(+) (with adjuvant) or MPSV4. The next 190 participants,
      enrolled in Stage 2, were randomized (4:1) to receive either MenACWY-CRM(-)
      (without adjuvant) or MPSV4. Safety data were collected using diary cards and
      active surveillance. Human complement serum bactericidal activity (hSBA) titers
      were measured 1 and 12 months postvaccination. RESULTS: MenACWY-CRM and MPSV4
      vaccines were well tolerated (local reactions, 63%-71% vs. 60%-62%; systemic
      reactions, 44%-56% vs. 46%-59%, respectively). One month postvaccination, similar
      hSBA titers were observed with the adjuvanted and nonadjuvanted MenACWY-CRM. The
      immunogenicity of MenACWY-CRM(-), measured by geometric mean titer, was
      significantly (P < 0.05) greater than that of MPSV4 for all 4 vaccine serogroups
      at 1 month. The percentage of subjects with hSBA titers > or =1:4 was also
      significantly greater (P < 0.01) for MenACWY-CRM(-) recipients for serogroups A,
      C, and Y and noninferior for W-135. The proportions of MenACWY-CRM(-) recipients
      with hSBA titers > or =1:4 to the vaccine serogroups at 1 month were 84% to 96%
      and geometric mean titers were 34 to 100. The percentage of subjects with hSBA
      titers > or =1:4 was significantly (P < 0.01) greater than MPSV4 for serogroups
      C, W-135, and Y 12 months postvaccination. CONCLUSIONS: MenACWY-CRM was well
      tolerated and immunogenic, with evidence of persistence of bactericidal
      antibodies for at least 12 months postvaccination.

PMID- 19116604
TI  - Association of serotype of Streptococcus pneumoniae with risk of severe and fatal
      outcome.
AB  - BACKGROUND: Invasive pneumococcal disease (IPD) in children may manifest as
      bacteremia/sepsis, bacteremic pneumonia, or meningitis, with serious outcomes
      that include hospitalization, neurologic sequelae, or death. The risk of severe
      or fatal outcome of disease is associated with host-related factors, such as age
      or comorbid conditions. Furthermore, there is an ongoing discussion about
      organism-related factors, such as the pneumococcal serotype. METHODS: Data on 494
      children aged <16 years hospitalized for IPD between 1997 and 2003 in pediatric
      hospitals in Germany were analyzed. Serotype specific case-fatality rates and
      rates of severe outcome were compared using standardized mortality ratios (SMR).
      The risk of severe or fatal outcome for the serotype with the highest case
      fatality rate was further analyzed using multivariate logistic regression
      adjusting for age younger than 1 year, meningitis, sex, and immunocompromised
      status as potential confounders. RESULTS: The overall case-fatality rate was 5.3%
      and the rate of severe outcome was 17.0%. Serotype 7F had the highest case
      fatality rate (14.8%, SMR 3.1), followed by serotypes 23F (8.3%, SMR 1.7) and 3
      (8.3%, SMR 1.7). The highest rate of severe outcome was also observed for 7F
      (40.7%, SMR 2.4). Multivariate analysis showed an odds ratio of 4.3 (1.3-14.7)
      for fatal outcome and 4.0 (1.6-10.4) for severe outcome comparing 7F to all other
      serotypes. CONCLUSIONS: In this study population, serotype 7F accounted for a
      higher risk of severe and fatal outcome than other serotypes of Streptococcus
      pneumoniae. In describing the epidemiology of IPD, the serotype-specific risk for
      severe or fatal outcome is an important complement to other serotype-specific
      aspects like incidence and antibiotic resistance pattern.

PMID- 19116605
TI  - The changing burden of pediatric bloodstream infections in Calgary, Canada, 2000
      2006.
AB  - BACKGROUND: The epidemiology of pediatric bloodstream infection has not been well
      defined in general populations. The primary objective of this study was to
      describe the burden of illness of pediatric bloodstream infections in a large
      Canadian region and secondarily to assess the effect of implementation of
      universal infant immunization with 7-valent pneumococcal conjugate vaccine (PCV7)
      in 2002. METHODS: Surveillance for all bloodstream infections was conducted among
      pediatric (<18 years) residents of the Calgary Health Region during 2000-2006.
      RESULTS: Nine hundred ninety-five episodes of bloodstream infection occurred for
      an overall annual incidence of 53.7 per 100,000. Forty-eight percent were
      community-acquired, 27% were nosocomial-acquired, and 26% were healthcare
      associated community onset. The risk for bloodstream infection was highest in
      neonates. The annual incidence of bloodstream infection changed significantly (P
      < 0.001) and was attributed to a decreasing incidence of community (P = 0.001)
      acquired disease. The most common species isolated were Streptococcus pneumoniae,
      Staphylococcus aureus, and Escherichia coli. Overall rates of pneumococcal
      infection decreased significantly in the post-PCV7 era (2004-2006) as compared
      with pre-PCV7 era (2000-2001) (4.6 vs. 13.6 per 100,000; P < 0.0001). This was
      even more pronounced in the subset with community-acquired disease (3.0 vs. 11.3
      per 100,000; P < 0.0001) especially in the age group between 1 and 23 months of
      age (7.3 vs. 58.9 per 100,000; P < 0.0001). The overall mortality rate was 2 per
      100,000/yr. CONCLUSIONS: Bloodstream infections are an important cause of disease
      in children. Implementation of PCV7 has been associated with a significant
      reduction in the overall burden of disease.

PMID- 19116606
TI  - Reduced hospitalizations for acute myocardial infarction after implementation of
      a smoke-free ordinance--City of Pueblo, Colorado, 2002-2006.
AB  - Exposure to secondhand smoke (SHS) has immediate adverse cardiovascular effects,
      and prolonged exposure can cause coronary heart disease. Nine studies have
      reported that laws making indoor workplaces and public places smoke-free were
      associated with rapid, sizeable reductions in hospitalizations for acute
      myocardial infarction (AMI). However, most studies examined hospitalizations for
      1 year or less after laws were implemented; thus, whether the observed effect was
      sustained over time was unknown. The Pueblo Heart Study examined the impact of a
      municipal smoke-free ordinance in the city of Pueblo, Colorado, that took effect
      on July 1, 2003. The rate of AMI hospitalizations for city residents decreased
      27%, from 257 per 100,000 person-years during the 18 months before the
      ordinance's implementation to 187 during the 18 months after it (the Phase I post
      implementation period). This report extends that analysis for an additional 18
      months through June 30, 2006 (the Phase II post-implementation period). The rate
      of AMI hospitalizations among city residents continued to decrease to 152 per
      100,000 person-years, a decline of 19% and 41% from the Phase I post
      implementation and pre-implementation period, respectively. No significant
      changes were observed in two comparison areas. These findings suggest that smoke
      free policies can result in reductions in AMI hospitalizations that are sustained
      over a 3-year period and that these policies are important in preventing
      morbidity and mortality associated with heart disease. This effect likely is
      mediated through reduced SHS exposure among nonsmokers and reduced smoking, with
      the former making the larger contribution.

PMID- 19116607
TI  - Campylobacter jejuni infection associated with unpasteurized milk and cheese-
      Kansas, 2007.
AB  - On October 26, 2007, a family health clinic nurse informed the Kansas Department
      of Health and Environment (KDHE) that Campylobacter jejuni had been isolated from
      two ill persons from different families who were members of a closed community in
      a rural Kansas county. By October 29, 17 additional members of the community had
      reported gastrointestinal illness and visited the clinic within a week. All 19
      persons reported consuming fresh cheese* on October 20 that was made the same day
      at a community fair from unpasteurized milk obtained from a local dairy. This
      report summarizes the findings of an investigation by KDHE and the local health
      department to determine the source and extent of the outbreak. Eating fresh
      cheese at the fair was the only exposure associated with illness (relative risk
      [RR] = 13.9). Of 101 persons who ate the cheese, 67 (66%) became ill. C. jejuni
      isolates from two ill persons had indistinguishable pulsed-field gel
      electrophoresis (PFGE) patterns, and the isolate from a third ill person was
      nearly identical to the other two. Although all samples of cheese tested negative
      for Campylobacter, results of the epidemiologic investigation found an
      association between illness and consumption of fresh cheese made from
      unpasteurized milk. To minimize the risk for illness associated with milkborne
      pathogens, unpasteurized milk and milk products should not be consumed.

PMID- 19116608
TI  - Underground coal mining disasters and fatalities--United States, 1900-2006.
AB  - During a 5-month period in 2006, three underground coal mining incidents in the
      United States resulted in the deaths of 19 miners. All three incidents received
      nationwide attention, particularly the Sago Mine disaster, which occurred on
      January 2 and resulted in the deaths of 12 miners. The other two incidents, which
      occurred at the Alma No. 1 Mine on January 19 and the Darby No. 1 Mine on May 20,
      resulted in the deaths of two miners and five miners, respectively. The
      occurrence of three fatal incidents in 5 months was a departure from recent
      trends in underground coal mining safety. Before 2006, the number of mining
      disasters had decreased from a high of 20 in 1909 to an average of one every 4
      years during 1985--2005. Deaths resulting from the three incidents were the
      stimulus for the Mine Improvement and New Emergency Response Act of 2006 (MINER
      Act), which amended the Mine Safety and Health Act of 1977 to improve safety,
      health, preparedness, and emergency response in U.S. mining. This report briefly
      describes the three 2006 mining incidents, reviews mining disasters in the United
      States during 1900--2006, and traces the effect of the disasters and the 2006
      incidents on mining health and safety regulations.

PMID- 19116609
TI  - Predicting free energy changes using structural ensembles.

PMID- 19116610
TI  - Putting super-resolution fluorescence microscopy to work.

PMID- 19116611
TI  - Microscopy and its focal switch.
AB  - Until not very long ago, it was widely accepted that lens-based (far-field)
      optical microscopes cannot visualize details much finer than about half the
      wavelength of light. The advent of viable physical concepts for overcoming the
      limiting role of diffraction in the early 1990s set off a quest that has led to
      readily applicable and widely accessible fluorescence microscopes with nanoscale
      spatial resolution. Here I discuss the principles of these methods together with
      their differences in implementation and operation. Finally, I outline potential
      developments.

PMID- 19116612
TI  - Inhibiting microRNA function in vivo.

PMID- 19116614
TI  - High-throughput screening: designer screens.

PMID- 19116613
TI  - Literature-curated protein interaction datasets.
AB  - High-quality datasets are needed to understand how global and local properties of
      protein-protein interaction, or 'interactome', networks relate to biological
      mechanisms, and to guide research on individual proteins. In an evaluation of
      existing curation of protein interaction experiments reported in the literature,
      we found that curation can be error-prone and possibly of lower quality than
      commonly assumed.

PMID- 19116617
TI  - News feature: 2008 in reflection.

PMID- 19116615
TI  - Enteric infection meets intestinal function: how bacterial pathogens cause
      diarrhoea.
AB  - Infectious diarrhoea is a significant contributor to morbidity and mortality
      worldwide. In bacterium-induced diarrhoea, rapid loss of fluids and electrolytes
      results from inhibition of the normal absorptive function of the intestine as
      well as the activation of secretory processes. Advances in the past 10 years in
      the fields of gastrointestinal physiology, innate immunity and enteric bacterial
      virulence mechanisms highlight the multifactorial nature of infectious diarrhoea.
      This review explores the various mechanisms that contribute to loss of fluids and
      electrolytes following bacterial infections, and attempts to link these events to
      specific virulence factors and toxins.

PMID- 19116619
TI  - Regulatory watch: FDA PDUFA goals missed.

PMID- 19116616
TI  - Reconstruction of biochemical networks in microorganisms.
AB  - Systems analysis of metabolic and growth functions in microbial organisms is
      rapidly developing and maturing. Such studies are enabled by reconstruction, at
      the genomic scale, of the biochemical reaction networks that underlie cellular
      processes. The network reconstruction process is organism specific and is based
      on an annotated genome sequence, high-throughput network-wide data sets and
      bibliomic data on the detailed properties of individual network components. Here
      we describe the process that is currently used to achieve comprehensive network
      reconstructions and discuss how these reconstructions are curated and validated.
      This review should aid the growing number of researchers who are carrying out
      reconstructions for particular target organisms.

PMID- 19116620
TI  - Regulatory watch: Non-inferiority-trial discussions impact new drug applications.

PMID- 19116621
TI  - Trial watch: Protease inhibitors show promise against HCV.

PMID- 19116622
TI  - European patent office's stem-cell decision.

PMID- 19116623
TI  - Steven Paul.

PMID- 19116624
TI  - Tetrabenazine.

PMID- 19116626
TI  - Allosteric modulators of GPCRs: a novel approach for the treatment of CNS
      disorders.
AB  - Despite G-protein-coupled receptors (GPCRs) being among the most fruitful targets
      for marketed drugs, intense discovery efforts for several GPCR subtypes have
      failed to deliver selective drug candidates. Historically, drug discovery
      programmes for GPCR ligands have been dominated by efforts to develop agonists
      and antagonists that act at orthosteric sites for endogenous ligands. However, in
      recent years, there have been tremendous advances in the discovery of novel
      ligands for GPCRs that act at allosteric sites to regulate receptor function.
      These compounds provide high selectivity, novel modes of efficacy and may lead to
      novel therapeutic agents for the treatment of multiple psychiatric and
      neurological human disorders.

PMID- 19116625
TI  - Is NF-kappaB a good target for cancer therapy? Hopes and pitfalls.
AB  - Nuclear factor kappaB (NF-kappaB) transcription factors have a key role in many
      physiological processes such as innate and adaptive immune responses, cell
      proliferation, cell death, and inflammation. It has become clear that aberrant
      regulation of NF-kappaB and the signalling pathways that control its activity are
      involved in cancer development and progression, as well as in resistance to
      chemotherapy and radiotherapy. This article discusses recent evidence from cancer
      genetics and cancer genome studies that support the involvement of NF-kappaB in
      human cancer, particularly in multiple myeloma. The therapeutic potential and
      benefit of targeting NF-kappaB in cancer, and the possible complications and
      pitfalls of such an approach, are explored.

PMID- 19116628
TI  - Clinical significance of colonic intraepithelial lymphocytosis in a pediatric
      population.
AB  - The significance of colonic intraepithelial lymphocytosis has been well described
      in adults, and is associated with lymphocytic colitis, untreated celiac disease,
      and medications, among others. Little is known about the meaning of colonic
      intraepithelial lymphocytosis in the pediatric population; this study examines
      this finding in a cohort of children. Twenty patients in whom colonic
      intraepithelial lymphocytosis was a prominent feature were identified from 1999
      to 2005. Colonic intraepithelial lymphocytosis was defined as 20 or more
      intraepithelial lymphocytes per 100 colonocytes present in at least one colonic
      mucosal biopsy. Each biopsy was examined for numbers of intraepithelial
      lymphocytes per 100 surface and crypt colonocytes; various architectural,
      inflammatory, and metaplastic changes were also noted. When available, concurrent
      duodenal and/or ileal biopsies were examined. Studied clinical parameters
      included indications for biopsy, clinical follow-up, final diagnosis,
      comorbidities, autoimmune serologies, and medications. A total of 121 colonic
      mucosal biopsies were examined in 20 patients who ranged from 1 to 17 years (mean
      10.2 years; 40% male). Common indications for endoscopy included diarrhea and
      abdominal pain. A mean of 29 (+/-22) intraepithelial lymphocytes per 100
      enterocytes were seen. Seven patients had colonic intraepithelial lymphocytosis
      as the only histologic finding. The remaining 13 patients had additional
      architectural, inflammatory, and metaplastic changes. The mean follow-up period
      was 14 months (range 1-48 months). Inflammatory bowel disease was diagnosed in 4
      of 20 patients and was seen chiefly in biopsies in which colonic intraepithelial
      lymphocytosis was associated with architectural or inflammatory changes. Common
      disease associations include celiac disease, lymphocytic colitis, and autoimmune
      enteropathy. Pediatric colonic intraepithelial lymphocytosis, in the absence of
      other histologic findings, is associated with various diseases, including celiac
      disease, lymphocytic colitis, and autoimmune enteropathy. Colonic intraepithelial
      lymphocytosis in the presence of other inflammatory changes indicates the
      possibility of idiopathic inflammatory bowel disease. These findings are similar
      to those seen in adults, with the exception of autoimmune enteropathy.

PMID- 19116627
TI  - Transient receptor potential channels: targeting pain at the source.
AB  - Pain results from the complex processing of neural signals at different levels of
      the central nervous system, with each signal potentially offering multiple
      opportunities for pharmacological intervention. A logical strategy for developing
      novel analgesics is to target the beginning of the pain pathway, and aim
      potential treatments directly at the nociceptors--the high-threshold primary
      sensory neurons that detect noxious stimuli. The largest group of receptors that
      function as noxious stimuli detectors in nociceptors is the transient receptor
      potential (TRP) channel family. This Review highlights evidence supporting
      particular TRP channels as targets for analgesics, indicates the likely efficacy
      profiles of TRP-channel-acting drugs, and discusses the development pathways
      needed to test candidates as analgesics in humans.

PMID- 19116629
TI  - Presence of endometrial adenocarcinoma in situ in complex atypical endometrial
      hyperplasia is associated with increased incidence of endometrial carcinoma in
      subsequent hysterectomy.
AB  - The distinction of complex atypical endometrial hyperplasia from endometrial
      adenocarcinoma is often problematic. Foci of back-to-back arrangement of glands
      or foci of cribriform arrangement of glands smaller than 2.1 mm in diameter are
      considered insufficient for the diagnosis of endometrial adenocarcinoma by some
      authors, and sufficient to be diagnosed as endometrial adenocarcinoma by other
      authors. We refer to these foci as endometrial adenocarcinoma in situ. In this
      study, we evaluated findings in subsequent hysterectomy in complex atypical
      endometrial hyperplasia patients with and without adenocarcinoma in situ. Follow
      up findings, including the presence or absence of endometrial adenocarcinoma in
      the hysterectomy specimen, the grade of the carcinoma and the depth of myometrial
      invasion were analyzed. Of the total 87 patients with complex atypical
      endometrial hyperplasia, 33 patients had adenocarcinoma in situ and 54 lacked
      adenocarcinoma in situ. Of 33 patients 22 (66%) with adenocarcinoma in situ had
      endometrial adenocarcinoma on subsequent hysterectomy vs 13 of 54 (24%) patients
      without adenocarcinoma in situ (P=0.0001). Myoinvasive endometrial adenocarcinoma
      was present in 20 of 33 (61%) patients with adenocarcinoma in situ vs 8 of the 54
      (15%) patients without adenocarcinoma in situ (P< or =0.0001). The depth of
      myometrial invasion in cases with myoinvasion was 24.5+19.4% in patients with
      adenocarcinoma in situ and 12.8+8.5% in patients without adenocarcinoma in situ
      (P=0.05). Among patients younger than age of 50, 5 of the 7 (71%) with
      adenocarcinoma in situ had myoinvasive carcinoma vs 2 of the 13 (15%) without
      adenocarcinoma in situ (P=0.02). The likelihood of finding endometrial
      adenocarcinoma in subsequent hysterectomy in patients with complex atypical
      endometrial hyperplasia is significantly increased if adenocarcinoma in situ is
      present in prior endometrial sampling. Endometrial adenocarcinomas in patients
      with adenocarcinoma in situ are far more frequently myoinvasive, and invade to a
      greater depth than endometrial adenocarcinomas seen in patients without
      adenocarcinoma in situ. Use of adenocarcinoma in situ terminology could lead to
      improved management of patients with complex atypical endometrial hyperplasia.

PMID- 19116630
TI  - Utility of the World Heath Organization classification criteria for the diagnosis
      of systemic mastocytosis in bone marrow.
AB  - In the World Health Organization classification, one major and four minor
      criteria are specified for the diagnosis of systemic mastocytosis. We report our
      experience using these criteria to diagnose systemic mastocytosis involving bone
      marrow. A total of 59 patients with clinically suspected systemic mastocytosis
      underwent comprehensive bone marrow examination, including immunophenotyping by
      immunohistochemistry and/or flow cytometry and molecular studies for KIT exon 17
      mutations. Serum tryptase levels were also assessed. Of these 59, 53 (90%)
      patients met the diagnostic criteria for systemic mastocytosis. In these
      patients, multifocal dense infiltrates of mast cells, the major criterion, was
      observed in 36 (68%) patients. Atypical mast cell morphology was observed in 53
      (100%), an aberrant immunophenotype was identified in 50 of 52 (96%), KIT
      mutation was present in 33 of 44 (75%), and an elevated serum tryptase (>20
      ng/ml) was detected in 44 of 52 (85%). In the six patients in which bone marrow
      examination could not confirm systemic mastocytosis, one had systemic
      mastocytosis involving spleen, one patient had chronic idiopathic myelofibrosis,
      and four had no specific diagnosis, but systemic mastocytosis was still
      considered most likely. Of these six patients, atypical mast cell morphology was
      identified in five, aberrant immunophenotype in five, KIT mutation in two, and
      elevated serum tryptase in two. None of these cases met the major criteria. We
      conclude that the World Health Organization criteria are useful for the diagnosis
      of systemic mastocytosis in bone marrow specimens. The results also show the
      relative values of traditional morphologic criteria (ie, major criterion) and the
      results of ancillary testing (ie, minor criteria). However, as illustrated by the
      case of splenic systemic mastocytosis as well as the patient with chronic
      idiopathic myelofibrosis, the current World Health Organization system is neither
      completely sensitive nor specific for systemic mastocytosis.

PMID- 19116631
TI  - ESCGT 2008: progress in clinical gene therapy.

PMID- 19116634
TI  - Can type VII collagen injections cure dystrophic epidermolysis bullosa?

PMID- 19116635
TI  - Phase ib trial of oncolytic herpes virus G207 shows safety of multiple injections
      and documents viral replication.

PMID- 19116636
TI  - TAGTC meets across the pond. 3rd Transatlantic Gene Therapy Consortium London,
      UK, 2-3 October 2007.

PMID- 19116637
TI  - Expression of hemoglobin in rodent neurons.
AB  - Hemoglobin is the major protein in red blood cells and transports oxygen from the
      lungs to oxygen-demanding tissues, like the brain. Mechanisms that facilitate the
      uptake of oxygen in the vertebrate brain are unknown. In invertebrates, neuronal
      hemoglobin serves as intracellular storage molecule for oxygen. Here, we show by
      immunohistochemistry that hemoglobin is specifically expressed in neurons of the
      cortex, hippocampus, and cerebellum of the rodent brain, but not in astrocytes
      and oligodendrocytes. The neuronal hemoglobin distribution is distinct from the
      neuroglobin expression pattern on both cellular and subcellular levels. Probing
      for low oxygen levels in the tissue, we provide evidence that hemoglobin alpha
      positive cells in direct neighborhood with hemoglobin alpha-negative cells
      display a better oxygenation than their neighbors and can be sharply
      distinguished from those. Neuronal hemoglobin expression is upregulated by
      injection or transgenic overexpression of erythropoietin and is accompanied by
      enhanced brain oxygenation under physiologic and hypoxic conditions. Thus we
      provide a novel mechanism for the neuroprotective actions of erythropoietin under
      ischemic-hypoxic conditions. We propose that neuronal hemoglobin expression is
      connected to facilitated oxygen uptake in neurons, and hemoglobin might serve as
      oxygen capacitator molecule.

PMID- 19116639
TI  - Are we really dressed to kill?

PMID- 19116641
TI  - NADPH oxidase in the kidney: a Janus in determining cell fate.
AB  - NADPH oxidase-derived reactive oxygen species are implicated in apoptosis in
      certain kidney cells. On the other hand, NADPH oxidase is also involved in
      promoting cell proliferation in the kidney. The two faces of NADPH oxidase in
      these situations prompt us to argue that the role of this enzyme in various
      kidney diseases needs to be addressed in a cell-specific manner.

PMID- 19116642
TI  - The Janus effect: two faces of aldosterone.
AB  - Inhibition of the nitric oxide pathway by N(omega)-nitro-l-arginine methyl ester
      (l-NAME) is well known to produce hypertension and proteinuria, but the
      mechanisms are less straightforward. Prolonged administration of
      mineralocorticoids mimics the pathological findings produced by l-NAME. Ikeda and
      colleagues provide a clue to the mechanism by showing that exposure to l-NAME
      increases plasma aldosterone 50-fold, and that spironolactone markedly attenuates
      the renal changes. Thus, chronic l-NAME exposure may turn out to be a model of
      mineralocorticoid excess.

PMID- 19116643
TI  - Improving clinical trial design for inquiries into the mechanisms of cyst growth
      in ADPKD.
AB  - Accurate and reliable estimates of kidney and cyst volume, the hallmark of
      disease progression in ADPKD are now available. These powerful and exciting tools
      make it possible to consider both short and long term randomized clinical trials
      in ADPKD at various stages of disease. Highlights of the work by Kistler and
      colleagues are now provided.

PMID- 19116644
TI  - Palladin is a dynamic actin-associated protein in podocytes.
AB  - Palladin, a cytoskeletal protein with essential functions for stress fiber
      formation, is found in developing and mature tissues, including the kidney. To
      define its role in the kidney, we measured its expression in mouse kidney and
      found it co-localized with F-actin in smooth muscle cells of renal arterial
      vessels, mesangial cells, and podocytes but not in tubular epithelium. Using
      immunoelectron microscopy, we confirmed that palladin was present in podocytes.
      In cultured mouse podocytes, palladin co-localized with F-actin in dense regions
      of stress fibers, focal adhesions, cell-cell contacts and motile cell margins.
      Transfection with the N-terminal half of palladin targeted it to F-actin
      containing structures in podocytes while the C-terminal half accumulated in the
      nucleus, a result also found for endogenous palladin in cultured cells after
      leptomycin B was used to block nuclear export. Green fluorescent protein (GFP)
      tagged palladin was found in dynamic ring-like F-actin structures and ruffles in
      cultured podocytes after stimulation with epidermal growth factor. Inhibition of
      palladin expression by transfection of an antisense construct reduced the
      formation of ring-like structures. Photo-bleaching analysis showed that GFP
      palladin turned over with a half-time of 10 s in focal adhesions and dense
      regions of stress fibers, suggesting that palladin is a dynamic scaffolding
      protein. Our study shows that palladin is expressed in podocytes and plays an
      important role in actin dynamics.

PMID- 19116645
TI  - Altered mental status in a transplant patient. Amantadine toxicity.

PMID- 19116646
TI  - Tc99m WCC identifies occult abscess in a polycystic kidney.

PMID- 19116647
TI  - Gap junction mediated intercellular metabolite transfer in the cochlea is
      compromised in connexin30 null mice.
AB  - Connexin26 (Cx26) and connexin30 (Cx30) are two major protein subunits that co
      assemble to form gap junctions (GJs) in the cochlea. Mutations in either one of
      them are the major cause of non-syndromic prelingual deafness in humans. Because
      the mechanisms of cochlear pathogenesis caused by Cx mutations are unclear, we
      investigated effects of Cx30 null mutation on GJ-mediated ionic and metabolic
      coupling in the cochlea of mice. A novel flattened cochlear preparation was used
      to directly assess intercellular coupling in the sensory epithelium of the
      cochlea. Double-electrode patch clamp recordings revealed that the absence of
      Cx30 did not significantly change GJ conductance among the cochlear supporting
      cells. The preserved electrical coupling is consistent with immunolabeling data
      showing extensive Cx26 GJs in the cochlea of the mutant mice. In contrast, dye
      diffusion assays showed that the rate and extent of intercellular transfer of
      multiple fluorescent dyes (including a non-metabolizable D-glucose analogue, 2
      NBDG) among cochlear supporting cells were severely reduced in Cx30 null mice.
      Since the sensory epithelium in the cochlea is an avascular organ, GJ-facilitated
      intercellular transfer of nutrient and signaling molecules may play essential
      roles in cellular homeostasis. To test this possibility, NBDG was used as a
      tracer to study the contribution of GJs in transporting glucose into the cochlear
      sensory epithelium when delivered systemically. NBDG uptake in cochlear
      supporting cells was significantly reduced in Cx30 null mice. The decrease was
      also observed with GJ blockers or glucose competition, supporting the specificity
      of our tests. These data indicate that GJs facilitate efficient uptake of glucose
      in the supporting cells. This study provides the first direct experimental
      evidence showing that the transfer of metabolically-important molecules in
      cochlear supporting cells is dependent on the normal function of GJs, thereby
      suggesting a novel pathogenesis process in the cochlea for Cx-mutation-linked
      deafness.

PMID- 19116648
TI  - Comparative developmental expression profiling of two C. elegans isolates.
AB  - Gene expression is known to change during development and to vary among
      genetically diverse strains. Previous studies of temporal patterns of gene
      expression during C. elegans development were incomplete, and little is known
      about how these patterns change as a function of genetic background. We used
      microarrays that comprehensively cover known and predicted worm genes to compare
      the landscape of genetic variation over developmental time between two isolates
      of C. elegans. We show that most genes vary in expression during development from
      egg to young adult, many genes vary in expression between the two isolates, and a
      subset of these genes exhibit isolate-specific changes during some developmental
      stages. This subset is strongly enriched for genes with roles in innate immunity.
      We identify several novel motifs that appear to play a role in regulating gene
      expression during development, and we propose functional annotations for many
      previously unannotated genes. These results improve our understanding of gene
      expression and function during worm development and lay the foundation for
      linkage studies of the genetic basis of developmental variation in gene
      expression in this important model organism.

PMID- 19116649
TI  - Demographic and clinical factors associated with response to smallpox vaccine in
      preimmunized volunteers.
AB  - CONTEXT: In March 2003, the French Ministry of Health implemented a program on
      preparedness and response to a biological attack using smallpox as weapon. This
      program included the establishment of a preoutbreak national team that could be
      revaccinated against smallpox. OBJECTIVE: To identify demographic and clinical
      factors associated with vaccination success defined as the presence of a pustule
      at the inoculation site at day 8 (days 7-9), with an undiluted vaccinia virus
      derived from a Lister strain among preimmunized volunteers. VOLUNTEERS AND
      METHODS: From March 2003 to November 2006, we have studied prospectively 226
      eligible volunteers. Demographic data were recorded for each volunteer (age, sex,
      number of previously smallpox vaccinations and date of the last vaccination).
      Smallpox vaccine adverse reactions were diagnosed on the basis of clinical
      examination performed at days 0, 7, 14, 21 and 28 after revaccination. RESULTS: A
      total of 226 volunteers (sex ratio H/F = 2.7) were revaccinated. Median age was
      45 years (range: 27-63 yrs). All volunteers completed follow-up. Median number of
      vaccinations before revaccination was 2 (range: 1-8). The median delay between
      time of the study and the last vaccination was 29 years (range; 18-60 yrs). Sixty
      one volunteers (27%) experienced one (n = 40) or more (n = 21) minor side effects
      during the 2-14 days after revaccination. Successful vaccination was noted in
      216/226 volunteers (95.6%) at day 8 and the median of the pustule diameter was 5
      mm (range: 1-20 mm). Size of the pustule at day 8 was correlated with age (p =
      0.03) and with the presence of axillary adenopathy after revaccination (p =
      0.007). Sex, number of prior vaccinations, delay between the last vaccination and
      revaccination, and local or systemic side effects with the exception of axillary
      adenopathy, were not correlated with the size of the pustule at day 8.
      CONCLUSIONS: Previously vaccinated volunteers can be successfully revaccinated
      with the Lister strain.

PMID- 19116650
TI  - Insect brains use image interpolation mechanisms to recognise rotated objects.
AB  - Recognising complex three-dimensional objects presents significant challenges to
      visual systems when these objects are rotated in depth. The image processing
      requirements for reliable individual recognition under these circumstances are
      computationally intensive since local features and their spatial relationships
      may significantly change as an object is rotated in the horizontal plane. Visual
      experience is known to be important in primate brains learning to recognise
      rotated objects, but currently it is unknown how animals with comparatively
      simple brains deal with the problem of reliably recognising objects when seen
      from different viewpoints. We show that the miniature brain of honeybees
      initially demonstrate a low tolerance for novel views of complex shapes (e.g.
      human faces), but can learn to recognise novel views of stimuli by interpolating
      between or 'averaging' views they have experienced. The finding that visual
      experience is also important for bees has important implications for
      understanding how three dimensional biologically relevant objects like flowers
      are recognised in complex environments, and for how machine vision might be
      taught to solve related visual problems.

PMID- 19116651
TI  - Concurrent generation of effector and central memory CD8 T cells during vaccinia
      virus infection.
AB  - It is generally thought that during the contraction phase of an acute anti-viral
      T cell reponse, the effector T cells that escape activation-induced cell death
      eventually differentiate into central memory T cells over the next several weeks.
      Here we report that antigen-specific CD8T cells with the phenotype and function
      of central memory cells develop concomitantly with effector T cells during
      vaccinia virus (vv) infection. As soon as 5 days after an intraperitoneal
      infection with vv, we could identify a subset of CD44(hi) and CD62L(+) vv
      specific CD8 T cells in the peritoneal exudate lymphocytes. This population
      constituted approximately 10% of all antigen-specific T cells and like central
      memory T cells, they also expressed high levels of CCR7 and IL-7R but expressed
      little granzyme B. Importantly, upon adoptive transfer into naive congenic hosts,
      CD62L(+), but not CD62L(-) CD8 T cells were able to expand and mediate a rapid
      recall response to a new vv challenge initiated 6 weeks after transfer,
      confirming that the CD62L(+) vv-specific CD8 T cells are bonafide memory cells.
      Our results are thus consistent with the branched differentiation model, where
      effector and memory cells develop simultaneously. These results are likely to
      have implications in the context of vaccine design, particularly those based on
      vaccinia virus recombinants.

PMID- 19116652
TI  - Opposing effects of sirtuins on neuronal survival: SIRT1-mediated neuroprotection
      is independent of its deacetylase activity.
AB  - BACKGROUND: Growing evidence suggests that sirtuins, a family of seven distinct
      NAD-dependent enzymes, are involved in the regulation of neuronal survival.
      Indeed, SIRT1 has been reported to protect against neuronal death, while SIRT2
      promotes neurodegeneration. The effect of SIRTs 3-7 on the regulation of neuronal
      survival, if any, has yet to be reported. METHODOLOGY AND PRINCIPAL FINDINGS: We
      examined the effect of expressing each of the seven SIRT proteins in healthy
      cerebellar granule neurons (CGNs) or in neurons induced to die by low potassium
      (LK) treatment. We report that SIRT1 protects neurons from LK-induced apoptosis,
      while SIRT2, SIRT3 and SIRT6 induce apoptosis in otherwise healthy neurons. SIRT5
      is generally localized to both the nucleus and cytoplasm of CGNs and exerts a
      protective effect. In a subset of neurons, however, SIRT5 localizes to the
      mitochondria and in this case it promotes neuronal death. Interestingly, the
      protective effect of SIRT1 in neurons is not reduced by treatments with
      nicotinamide or sirtinol, two pharmacological inhibitors of SIRT1.
      Neuroprotection was also observed with two separate mutant forms of SIRT1, H363Y
      and H355A, both of which lack deacetylase activity. Furthermore, LK-induced
      neuronal death was not prevented by resveratrol, a pharmacological activator of
      SIRT1, at concentrations at which it activates SIRT1. We extended our analysis to
      HT-22 neuroblastoma cells which can be induced to die by homocysteic acid
      treatment. While the effects of most of the SIRT proteins were similar to that
      observed in CGNs, SIRT6 was modestly protective against homocysteic acid toxicity
      in HT-22 cells. SIRT5 was generally localized in the mitochondria of HT-22 cells
      and was apoptotic. CONCLUSIONS/SIGNIFICANCE: Overall, our study makes three
      contributions - (a) it represents the first analysis of SIRT3-7 in the regulation
      of neuronal survival, (b) it shows that neuroprotection by SIRT1 can be mediated
      by a novel, non-catalytic mechanism, and (c) that subcellular localization may be
      an important determinant in the effect of SIRT5 on neuronal viability.

PMID- 19116653
TI  - Reassessment of CXCR4 chemokine receptor expression in human normal and
      neoplastic tissues using the novel rabbit monoclonal antibody UMB-2.
AB  - BACKGROUND: The CXCR4 chemokine receptor regulates migration and homing of cancer
      cells to specific metastatic sites. Determination of the CXCR4 receptor status
      will provide predictive information for disease prognosis and possible
      therapeutic intervention. However, previous attempts to localize CXCR4 using
      poorly characterized mouse monoclonal or rabbit polyclonal antibodies have
      produced predominant nuclear and occasional cytoplasmic staining but did not
      result in the identification of bona fide cell surface receptors.
      METHODOLOGY/PRINCIPAL FINDINGS: In the present study, we extensively
      characterized the novel rabbit monoclonal anti-CXCR4 antibody (clone UMB-2) using
      transfected cells and tissues from CXCR4-deficient mice. Specificity of UMB-2 was
      demonstrated by cell surface staining of CXCR4-transfected cells; translocation
      of CXCR4 immunostaining after agonist exposure; detection of a broad band
      migrating at M(r) 38,000-43,000 in Western blots of homogenates from CXCR4
      expressing cells; selective detection of the receptor in tissues from CXCR4+/+
      but not from CXCR4-/- mice; and abolition of tissue immunostaining by
      preadsorption of UMB-2 with its immunizing peptide. In formalin-fixed, paraffin
      embedded human tumor tissues, UMB-2 yielded highly effective plasma membrane
      staining of a subpopulation of tumor cells, which were often heterogeneously
      distributed throughout the tumor. A comparative analysis of the mouse monoclonal
      antibody 12G5 and other frequently used commercially available antibodies
      revealed that none of these was able to detect CXCR4 under otherwise identical
      conditions. CONCLUSIONS/SIGNIFICANCE: Thus, the rabbit monoclonal antibody UMB-2
      may prove of great value in the assessment of the CXCR4 receptor status in a
      variety of human tumors during routine histopathological examination.

PMID- 19116654
TI  - Evolutionary patterns and selective pressures of odorant/pheromone receptor gene
      families in teleost fishes.
AB  - BACKGROUND: Teleost fishes do not have a vomeronasal organ (VNO), and their
      vomeronasal receptors (V1Rs, V2Rs) are expressed in the main olfactory epithelium
      (MOE), as are odorant receptors (ORs) and trace amine-associated receptors
      (TAARs). In this study, to obtain insights into the functional distinction among
      the four chemosensory receptor families in teleost fishes, their evolutionary
      patterns were examined in zebrafish, medaka, stickleback, fugu, and spotted green
      pufferfish. METHODOLOGY/PRINCIPAL FINDINGS: Phylogenetic analysis revealed that
      many lineage-specific gene gains and losses occurred in the teleost fish TAARs,
      whereas only a few gene gains and losses have taken place in the teleost fish
      vomeronasal receptors. In addition, synonymous and nonsynonymous nucleotide
      substitution rate ratios (K(A)/K(S)) in TAARs tended to be higher than those in
      ORs and V2Rs. CONCLUSIONS/SIGNIFICANCE: Frequent gene gains/losses and high
      K(A)/K(S) in teleost TAARs suggest that receptors in this family are used for
      detecting some species-specific chemicals such as pheromones. Conversely,
      conserved repertoires of V1R and V2R families in teleost fishes may imply that
      receptors in these families perceive common odorants for teleosts, such as amino
      acids. Teleost ORs showed intermediate evolutionary pattern between TAARs and
      vomeronasal receptors. Many teleost ORs seem to be used for common odorants, but
      some ORs may have evolved to recognize lineage-specific odors.

PMID- 19116655
TI  - Negative regulation of syntaxin4/SNAP-23/VAMP2-mediated membrane fusion by
      Munc18c in vitro.
AB  - BACKGROUND: Translocation of the facilitative glucose transporter GLUT4 from an
      intracellular store to the plasma membrane is responsible for the increased rate
      of glucose transport into fat and muscle cells in response to insulin. This
      represents a specialised form of regulated membrane trafficking. Intracellular
      membrane traffic is subject to multiple levels of regulation by conserved
      families of proteins in all eukaryotic cells. Notably, all intracellular fusion
      events require SNARE proteins and Sec1p/Munc18 family members. Fusion of GLUT4
      containing vesicles with the plasma membrane of insulin-sensitive cells involves
      the SM protein Munc18c, and is regulated by the formation of syntaxin
      4/SNAP23/VAMP2 SNARE complexes. METHODOLOGY/PRINCIPAL FINDINGS: Here we have used
      biochemical approaches to characterise the interaction(s) of Munc18c with its
      cognate SNARE proteins and to examine the role of Munc18c in regulating liposome
      fusion catalysed by syntaxin 4/SNAP23/VAMP2 SNARE complex formation. We
      demonstrate that Munc18c makes contacts with both t- and v-SNARE proteins of this
      complex, and directly inhibits bilayer fusion mediated by the syntaxin
      4/SNAP23/VAMP2 SNARE complex. CONCLUSION/SIGNIFICANCE: Our reductionist approach
      has enabled us to ascertain a direct inhibitory role for Munc18c in regulating
      membrane fusion mediated by syntaxin 4/SNAP23/VAMP2 SNARE complex formation. It
      is important to note that two different SM proteins have recently been shown to
      stimulate liposome fusion mediated by their cognate SNARE complexes. Given the
      structural similarities between SM proteins, it seems unlikely that different
      members of this family perform opposing regulatory functions. Hence, our findings
      indicate that Munc18c requires a further level of regulation in order to
      stimulate SNARE-mediated membrane fusion.

PMID- 19116656
TI  - Spent culture medium from virulent Borrelia burgdorferi increases permeability of
      individually perfused microvessels of rat mesentery.
AB  - BACKGROUND: Lyme disease is a common vector-borne disease caused by the
      spirochete Borrelia burgdorferi (Bb), which manifests as systemic and targeted
      tissue inflammation. Both in vitro and in vivo studies have shown that Bb-induced
      inflammation is primarily host-mediated, via cytokine or chemokine production
      that promotes leukocyte adhesion/migration. Whether Bb produces mediators that
      can directly alter the vascular permeability in vivo has not been investigated.
      The objective of the present study was to investigate if Bb produces a
      mediator(s) that can directly activate endothelial cells resulting in increases
      in permeability in intact microvessels in the absence of blood cells.
      METHODOLOGY/PRINCIPAL FINDINGS: The effects of cell-free, spent culture medium
      from virulent (B31-A3) and avirulent (B31-A) B. burgdorferi on microvessel
      permeability and endothelial calcium concentration, [Ca(2+)](i), were examined in
      individually perfused rat mesenteric venules. Microvessel permeability was
      determined by measuring hydraulic conductivity (Lp). Endothelial [Ca(2+)](i), a
      necessary signal initiating hyperpermeability, was measured in Fura-2 loaded
      microvessels. B31-A3 spent medium caused a rapid and transient increase in Lp and
      endothelial [Ca(2+)](i). Within 2-5 min, the mean peak Lp increased to 5.6+/-0.9
      times the control, and endothelial [Ca(2+)](i) increased from 113+/-11 nM to a
      mean peak value of 324+/-35 nM. In contrast, neither endothelial [Ca(2+)](i) nor
      Lp was altered by B31-A spent medium. CONCLUSIONS/SIGNIFICANCE: A mediator(s)
      produced by virulent Bb under culture conditions directly activates endothelial
      cells, resulting in increases in microvessel permeability. Most importantly, the
      production of this mediator is associated with Bb virulence and is likely
      produced by one or more of the 8 plasmid(s) missing from strain B31-A.

PMID- 19116658
TI  - Large-scale differential proteome analysis in Plasmodium falciparum under drug
      treatment.
AB  - Proteome studies contribute markedly to our understanding of parasite biology,
      host-parasite interactions, and mechanisms of drug action. For most antimalarial
      drugs neither mode of action nor mechanisms of resistance development are fully
      elucidated although this would be important prerequisites for successfully
      developing urgently required novel antimalarials. Here, we establish a large
      scale quantitative proteomic approach to examine protein expression changes in
      trophozoite stages of the malarial parasite Plasmodium falciparum following
      chloroquine and artemisinin treatment. For this purpose SIL (stable isotope
      labeling) using (14)N-isoleucine and (13)C(6),(15)N(1)-isoleucine was optimized
      to obtain 99% atomic percent enrichment. Proteome fractionation with anion
      exchange chromatography was used to reduce sample complexity and increase
      quantitative coverage of protein expression. Tryptic peptides of subfractions
      were subjected to SCX/RP separation, measured by LC-MS/MS and quantified using
      the novel software tool Census. In drug treated parasites, we identified a total
      number of 1,253 proteins, thus increasing the overall number of proteins
      identified in the trophozoite stage by 30%. A relative quantification was
      obtained for more than 800 proteins. Under artemisinin and chloroquine treatment
      41 and 38 proteins respectively were upregulated (>1.5) whereas 14 and 8 proteins
      were down-regulated (<0.5). Apart from specifically regulated proteins we also
      identified sets of proteins which were regulated as a general response to drug
      treatment. The proteomic data was confirmed by Western blotting. The methodology
      described here allows for the efficient large-scale differential proteome
      analysis of P. falciparum to study the response to drug treatment or
      environmental changes. Only 100 microg of protein is required for the analysis
      suggesting that the method can also be transferred to other apicomplexan
      parasites.

PMID- 19116657
TI  - Differential requirements of two recA mutants for constitutive SOS expression in
      Escherichia coli K-12.
AB  - BACKGROUND: Repairing DNA damage begins with its detection and is often followed
      by elicitation of a cellular response. In E. coli, RecA polymerizes on ssDNA
      produced after DNA damage and induces the SOS Response. The RecA-DNA filament is
      an allosteric effector of LexA auto-proteolysis. LexA is the repressor of the SOS
      Response. Not all RecA-DNA filaments, however, lead to an SOS Response. Certain
      recA mutants express the SOS Response (recA(C)) in the absence of external DNA
      damage in log phase cells. METHODOLOGY/PRINCIPAL FINDINGS: Genetic analysis of
      two recA(C) mutants was used to determine the mechanism of constitutive SOS
      (SOS(C)) expression in a population of log phase cells using fluorescence of
      single cells carrying an SOS reporter system (sulAp-gfp). SOS(C) expression in
      recA4142 mutants was dependent on its initial level of transcription, recBCD,
      recFOR, recX, dinI, xthA and the type of medium in which the cells were grown.
      SOS(C) expression in recA730 mutants was affected by none of the mutations or
      conditions tested above. CONCLUSIONS/SIGNIFICANCE: It is concluded that not all
      recA(C) alleles cause SOS(C) expression by the same mechanism. It is hypothesized
      that RecA4142 is loaded on to a double-strand end of DNA and that the RecA
      filament is stabilized by the presence of DinI and destabilized by RecX. RecFOR
      regulate the activity of RecX to destabilize the RecA filament. RecA730 causes
      SOS(C) expression by binding to ssDNA in a mechanism yet to be determined.

PMID- 19116659
TI  - Genetically-directed, cell type-specific sparse labeling for the analysis of
      neuronal morphology.
AB  - BACKGROUND: In mammals, genetically-directed cell labeling technologies have not
      yet been applied to the morphologic analysis of neurons with very large and
      complex arbors, an application that requires extremely sparse labeling and that
      is only rendered practical by limiting the labeled population to one or a few
      predetermined neuronal subtypes. METHODS AND FINDINGS: In the present study we
      have addressed this application by using CreER technology to non-invasively label
      very small numbers of neurons so that their morphologies can be fully visualized.
      Four lines of IRES-CreER knock-in mice were constructed to permit labeling
      selectively in cholinergic or catecholaminergic neurons [choline
      acetyltransferase (ChAT)-IRES-CreER or tyrosine hydroxylase (TH)-IRES-CreER],
      predominantly in projection neurons [neurofilament light chain (NFL)-IRES-CreER],
      or broadly in neurons and some glia [vesicle-associated membrane protein2 (VAMP2)
      IRES-CreER]. When crossed to the Z/AP reporter and exposed to 4-hydroxytamoxifen
      in the early postnatal period, the number of neurons expressing the human
      placental alkaline phosphatase reporter can be reproducibly lowered to fewer than
      50 per brain. Sparse Cre-mediated recombination in ChAT-IRES-CreER;Z/AP mice
      shows the full axonal and dendritic arbors of individual forebrain cholinergic
      neurons, the first time that the complete morphologies of these very large
      neurons have been revealed in any species. CONCLUSIONS: Sparse genetically
      directed, cell type-specific neuronal labeling with IRES-creER lines should prove
      useful for studying a wide variety of questions in neuronal development and
      disease.

PMID- 19116660
TI  - Model of For3p-mediated actin cable assembly in fission yeast.
AB  - Formin For3p nucleates actin cables at the tips of fission yeast cells for
      polarized cell growth. The results of prior experiments have suggested a possible
      mechanism for actin cable assembly that involves association of For3p near cell
      tips, For3p-mediated actin polymerization, retrograde flow of actin cables toward
      the cell center, For3p dissociation from cell tips, and cable disassembly. We
      used analytical and computational modeling to test the validity and implications
      of the proposed coupled For3p/actin mechanism. We compared the model to prior
      experiments quantitatively and generated predictions for the expected behavior of
      the actin cable system upon changes of parameter values. We found that the model
      generates stable steady states with realistic values of rate constants and actin
      and For3p concentrations. Comparison of our results to previous experiments
      monitoring the FRAP of For3p-3GFP and the response of actin cables to treatments
      with actin depolymerizing drugs provided further support for the model. We
      identified the set of parameter values that produces results in agreement with
      experimental observations. We discuss future experiments that will help test the
      model's predictions and eliminate other possible mechanisms. The results of the
      model suggest that flow of actin cables may establish actin and For3p
      concentration gradients in the cytoplasm that could be important in global cell
      patterning.

PMID- 19116661
TI  - A naturally occurring mutation in ropB suppresses SpeB expression and reduces
      M1T1 group A streptococcal systemic virulence.
AB  - Epidemiological studies of group A streptococcus (GAS) have noted an inverse
      relationship between SpeB expression and invasive disease. However, the role of
      SpeB in the course of infection is still unclear. In this study we utilize a SpeB
      negative M1T1 clinical isolate, 5628, with a naturally occurring mutation in the
      gene encoding the regulator RopB, to elucidate the role of RopB and SpeB in
      systemic virulence. Allelic exchange mutagenesis was used to replace the mutated
      ropB allele in 5628 with the intact allele from the well characterized isolate
      5448. The inverse allelic exchange was also performed to replace the intact ropB
      in 5448 with the mutated allele from 5628. An intact ropB was found to be
      essential for SpeB expression. While the ropB mutation was shown to have no
      effect on hemolysis of RBC's, extracellular DNase activity or survival in the
      presence of neutrophils, strains with the mutated ropB allele were less virulent
      in murine systemic models of infection. An isogenic SpeB knockout strain
      containing an intact RopB showed similarly reduced virulence. Microarray analysis
      found genes of the SpeB operon to be the primary target of RopB regulation. These
      data show that an intact RopB and efficient SpeB production are necessary for
      systemic infection with GAS.

PMID- 19116662
TI  - Genome scan of M. tuberculosis infection and disease in Ugandans.
AB  - Tuberculosis (TB), caused by Mycobacterium tuberculosis (Mtb), is an enduring
      public health problem globally, particularly in sub-Saharan Africa. Several
      studies have suggested a role for host genetic susceptibility in increased risk
      for TB but results across studies have been equivocal. As part of a household
      contact study of Mtb infection and disease in Kampala, Uganda, we have taken a
      unique approach to the study of genetic susceptibility to TB, by studying three
      phenotypes. First, we analyzed culture confirmed TB disease compared to latent
      Mtb infection (LTBI) or lack of Mtb infection. Second, we analyzed resistance to
      Mtb infection in the face of continuous exposure, defined by a persistently
      negative tuberculin skin test (PTST-); this outcome was contrasted to LTBI.
      Third, we analyzed an intermediate phenotype, tumor necrosis factor-alpha
      (TNFalpha) expression in response to soluble Mtb ligands enriched with molecules
      secreted from Mtb (culture filtrate). We conducted a full microsatellite genome
      scan, using genotypes generated by the Center for Medical Genetics at Marshfield.
      Multipoint model-free linkage analysis was conducted using an extension of the
      Haseman-Elston regression model that includes half sibling pairs, and HIV status
      was included as a covariate in the model. The analysis included 803 individuals
      from 193 pedigrees, comprising 258 full sibling pairs and 175 half sibling pairs.
      Suggestive linkage (p<10(-3)) was observed on chromosomes 2q21-2q24 and 5p13-5q22
      for PTST-, and on chromosome 7p22-7p21 for TB; these findings for PTST- are novel
      and the chromosome 7 region contains the IL6 gene. In addition, we replicated
      recent linkage findings on chromosome 20q13 for TB (p = 0.002). We also observed
      linkage at the nominal alpha = 0.05 threshold to a number of promising candidate
      genes, SLC11A1 (PTST- p = 0.02), IL-1 complex (TB p = 0.01), IL12BR2 (TNFalpha p
      = 0.006), IL12A (TB p = 0.02) and IFNGR2 (TNFalpha p = 0.002). These results
      confirm not only that genetic factors influence the interaction between humans
      and Mtb but more importantly that they differ according to the outcome of that
      interaction: exposure but no infection, infection without progression to disease,
      or progression of infection to disease. Many of the genetic factors for each of
      these stages are part of the innate immune system.

PMID- 19116663
TI  - The Maestro (Mro) gene is dispensable for normal sexual development and fertility
      in mice.
AB  - The mammalian gonad arises as a bipotential primordium from which a testis or
      ovary develops depending on the chromosomal sex of the individual. We have
      previously used DNA microarrays to screen for novel genes controlling the
      developmental fate of the indifferent embryonic mouse gonad. Maestro (Mro), which
      encodes a HEAT-repeat protein, was originally identified as a gene exhibiting
      sexually dimorphic expression during mouse gonad development. Wholemount in situ
      hybridisation analysis revealed Mro to be expressed in the embryonic male gonad
      from approximately 11.5 days post coitum, prior to overt sexual differentiation.
      No significant expression was detected in female gonads at the same developmental
      stage. In order to address its physiological function, we have generated mice
      lacking Maestro using gene targeting. Male and female mice homozygous for a Mro
      null allele are viable and fertile. We examined gonad development in homozygous
      male embryos in detail and observed no differences when compared to wild-type
      controls. Immunohistochemical analysis of homozygous mutant testes of adult mice
      revealed no overt abnormalities. Expression profiling using DNA microarrays also
      indicated no significant differences between homozygote embryonic male gonads and
      controls. We conclude that Maestro is dispensable for normal male sexual
      development and fertility in laboratory mice; however, the Mro locus itself does
      have utility as a site for insertion of transgenes for future studies in the
      fields of sexual development and Sertoli cell function.

PMID- 19116664
TI  - Topoisomerase IIbeta activates a subset of neuronal genes that are repressed in
      AT-rich genomic environment.
AB  - DNA topoisomerase II (topo II) catalyzes a strand passage reaction in that one
      duplex is passed through a transient brake or gate in another. Completion of late
      stages of neuronal development depends on the presence of active beta isoform
      (topo IIbeta). The enzyme appears to aid the transcriptional induction of a
      limited number of genes essential for neuronal maturation. However, this
      selectivity and underlying molecular mechanism remains unknown. Here we show a
      strong correlation between the genomic location of topo IIbeta action sites and
      the genes it regulates. These genes, termed group A1, are functionally biased
      towards membrane proteins with ion channel, transporter, or receptor activities.
      Significant proportions of them encode long transcripts and are juxtaposed to a
      long AT-rich intergenic region (termed LAIR). We mapped genomic sites directly
      targeted by topo IIbeta using a functional immunoprecipitation strategy. These
      sites can be classified into two distinct classes with discrete local GC
      contents. One of the classes, termed c2, appears to involve a strand passage
      event between distant segments of genomic DNA. The c2 sites are concentrated both
      in A1 gene boundaries and the adjacent LAIR, suggesting a direct link between the
      action sites and the transcriptional activation. A higher-order chromatin
      structure associated with AT richness and gene poorness is likely to serve as a
      silencer of gene expression, which is abrogated by topo IIbeta releasing nearby
      genes from repression. Positioning of these genes and their control machinery may
      have developed recently in vertebrate evolution to support higher functions of
      central nervous system.

PMID- 19116665
TI  - Lrp4 modulates extracellular integration of cell signaling pathways in
      development.
AB  - The extent to which cell signaling is integrated outside the cell is not
      currently appreciated. We show that a member of the low-density receptor-related
      protein family, Lrp4 modulates and integrates Bmp and canonical Wnt signalling
      during tooth morphogenesis by binding the secreted Bmp antagonist protein Wise.
      Mouse mutants of Lrp4 and Wise exhibit identical tooth phenotypes that include
      supernumerary incisors and molars, and fused molars. We propose that the
      Lrp4/Wise interaction acts as an extracellular integrator of epithelial
      mesenchymal cell signaling. Wise, secreted from mesenchyme cells binds to BMP's
      and also to Lrp4 that is expressed on epithelial cells. This binding then results
      in the modulation of Wnt activity in the epithelial cells. Thus in this context
      Wise acts as an extracellular signaling molecule linking two signaling pathways.
      We further show that a downstream mediator of this integration is the Shh
      signaling pathway.

PMID- 19116666
TI  - Origins of the Xylella fastidiosa prophage-like regions and their impact in
      genome differentiation.
AB  - Xylella fastidiosa is a Gram negative plant pathogen causing many economically
      important diseases, and analyses of completely sequenced X. fastidiosa genome
      strains allowed the identification of many prophage-like elements and possibly
      phage remnants, accounting for up to 15% of the genome composition. To better
      evaluate the recent evolution of the X. fastidiosa chromosome backbone among
      distinct pathovars, the number and location of prophage-like regions on two
      finished genomes (9a5c and Temecula1), and in two candidate molecules (Ann1 and
      Dixon) were assessed. Based on comparative best bidirectional hit analyses, the
      majority (51%) of the predicted genes in the X. fastidiosa prophage-like regions
      are related to structural phage genes belonging to the Siphoviridae family.
      Electron micrograph reveals the existence of putative viral particles with
      similar morphology to lambda phages in the bacterial cell in planta. Moreover,
      analysis of microarray data indicates that 9a5c strain cultivated under stress
      conditions presents enhanced expression of phage anti-repressor genes, suggesting
      switches from lysogenic to lytic cycle of phages under stress-induced situations.
      Furthermore, virulence-associated proteins and toxins are found within these
      prophage-like elements, thus suggesting an important role in host adaptation.
      Finally, clustering analyses of phage integrase genes based on multiple alignment
      patterns reveal they group in five lineages, all possessing a tyrosine
      recombinase catalytic domain, and phylogenetically close to other integrases
      found in phages that are genetic mosaics and able to perform generalized and
      specialized transduction. Integration sites and tRNA association is also
      evidenced. In summary, we present comparative and experimental evidence
      supporting the association and contribution of phage activity on the
      differentiation of Xylella genomes.

PMID- 19116667
TI  - Morphine exacerbates HIV-1 Tat-induced cytokine production in astrocytes through
      convergent effects on [Ca(2+)](i), NF-kappaB trafficking and transcription.
AB  - Astroglia are key cellular sites where opiate drug signals converge with the
      proinflammatory effects of HIV-1 Tat signals to exacerbate HIV encephalitis.
      Despite this understanding, the molecular sites of convergence driving opiate
      accelerated neuropathogenesis have not been deciphered. We therefore explored
      potential points of interaction between the signaling pathways initiated by HIV-1
      Tat and opioids in striatal astrocytes. Profiling studies screening 152
      transcription factors indicated that the nuclear factor-kappa B (NF-kappaB)
      subunit, c-Rel, was a likely candidate for Tat or Tat plus opiate-induced
      increases in cytokine and chemokine production by astrocytes. Pretreatment with
      the NF-kappaB inhibitor parthenolide provided evidence that Tat+/-morphine
      induced release of MCP-1, IL-6 and TNF-alpha by astrocytes is NF-kappaB
      dependent. The nuclear export inhibitor, leptomycin B, blocked the
      nucleocytoplasmic shuttling of NF-kappaB; causing p65 (RelA) accumulation in the
      nucleus, and significantly attenuated cytokine production in Tat+/-morphine
      exposed astrocytes. Similarly, chelating intracellular calcium ([Ca(2+)](i))
      blocked Tat+/-morphine-evoked MCP-1 and IL-6 release, while artificially
      increasing the concentration of extracellular Ca(2+) reversed this effect. Taken
      together, these results demonstrate that: 1) exposure to Tat+/-morphine is
      sufficient to activate NF-kappaB and cytokine production, 2) the release of MCP-1
      and IL-6 by Tat+/-morphine are highly Ca(2+)-dependent, while TNF-alpha appears
      to be less affected by the changes in [Ca(2+)](i), and 3) in the presence of Tat,
      exposure to opiates augments Tat-induced NF-kappaB activation and cytokine
      release through a Ca(2+)-dependent pathway.

PMID- 19116668
TI  - Validating discovered Cis-acting regulatory genetic variants: application of an
      allele specific expression approach to HapMap populations.
AB  - BACKGROUND: Localising regulatory variants that control gene expression is a
      challenge for genome research. Several studies have recently identified non
      coding polymorphisms associated with inter-individual differences in gene
      expression. These approaches rely on the identification of signals of association
      against a background of variation due to other genetic and environmental factors.
      A complementary approach is to use an Allele-Specific Expression (ASE) assay,
      which is more robust to the effects of environmental variation and trans-acting
      genetic factors. METHODOLOGY/PRINCIPAL FINDINGS: Here we apply an ASE method
      which utilises heterozygosity within an individual to compare expression of the
      two alleles of a gene in a single cell. We used individuals from three HapMap
      population groups and analysed the allelic expression of genes with cis
      regulatory regions previously identified using total gene expression studies. We
      were able to replicate the results in five of the six genes tested, and refined
      the cis- associated regions to a small number of variants. We also showed that by
      using multi-populations it is possible to refine the associated cis-effect DNA
      regions. CONCLUSIONS/SIGNIFICANCE: We discuss the efficacy and drawbacks of both
      total gene expression and ASE approaches in the discovery of cis-acting variants.
      We show that the ASE approach has significant advantages as it is a cleaner
      representation of cis-acting effects. We also discuss the implication of using
      different populations to map cis-acting regions and the importance of finding
      regulatory variants which contribute to human phenotypic variation.

PMID- 19116669
TI  - An epididymis-specific secretory protein HongrES1 critically regulates sperm
      capacitation and male fertility.
AB  - Mammalian sperm capacitation is an essential prerequisite to fertilizion.
      Although progress had been made in understanding the physiology and biochemistry
      of capacitation, little is known about the potential roles of epididymal proteins
      during this process. Here we report that HongrES1, a new member of the SERPIN
      (serine proteinase inhibitor) family exclusively expressed in the rat cauda
      epididymis and up-regulated by androgen, is secreted into the lumen and covers
      the sperm head. Co-culture of caudal sperms with HongrES1 antibody in vitro
      resulted in a significant increase in the percentage of capacitated spermatozoa.
      Furthermore, the percentage of capacitated spermatozoa clearly increased in rats
      when HongrES1 was down-regulated by RNAi in vivo. Remarkably, knockdown of
      HongrES1 in vivo led to reduced fertility accompanied with deformed appearance of
      fetuses and pups. These results identify HongrES1 as a novel and critical
      molecule in the regulation of sperm capacitation and male fertility.

PMID- 19116670
TI  - Calnexin is not essential for mammalian rod opsin biogenesis.
AB  - PURPOSE: Misfolding mutations in rod opsin are a major cause of the inherited
      blindness retinitis pigmentosa. Therefore, understanding the role of molecular
      chaperones in facilitating rod opsin biogenesis and the response to mutant rod
      opsin is important for retinal disease and fundamental retinal cell biology. A
      recent report has shown that Drosophila rhodopsin Rh1 requires calnexin (Cnx) for
      its maturation and correct localization to R1-6 rhabdomeres. In this report, we
      investigate the role of Cnx in the processing of wild-type and mutant mammalian
      rod opsin. METHODS: Mouse embryonic fibroblasts (MEFs) from control mice (WT) and
      mice that express a truncated dysfunctional version of Cnx (sCnx) were used to
      assess the role of Cnx in the biogenesis, maturation, degradation, and
      aggregation of mutant and wild-type rod opsin. The mutant P23H rod opsin was used
      as a prototypical class II misfolding mutant as it is retained in the endoplasmic
      reticulum (ER) and is either degraded by ER associated degradation (ERAD) or
      forms aggregates that coalesce to form intracellular inclusions. RESULTS: Wild
      type rod opsin protein translocated normally to the plasma membrane in both cell
      lines. In contrast, P23H rod opsin was retained in the ER in both cell lines. The
      only difference observed in rod opsin processing between the WT and sCnx MEFs was
      a small increase in the incidence of P23H intracellular inclusions in the sCnx
      cells. This did not appear to be specific for rod opsin, however, as non-rod
      opsin-expressing sCnx cells also had an increased incidence of ubiquitylated
      inclusions. CONCLUSIONS: Our data show that, unlike Drosophila Rh1, mammalian rod
      opsin biogenesis does not appear to have an absolute requirement for Cnx. Other
      chaperones are likely to be more important for mammalian rod opsin biogenesis and
      quality control.

PMID- 19116671
TI  - MULTISCALE TWO-DIMENSIONAL MODELING OF A MOTILE SIMPLE-SHAPED CELL.
AB  - Cell crawling is an important biological phenomenon underlying coordinated cell
      movement in morphogenesis, cancer, and wound healing. In recent decades the
      process of cell crawling has been experimentally and theoretically dissected into
      further subprocesses: protrusion of the cell at its leading edge, retraction of
      the cell body, and graded adhesion. A number of one-dimensional (1-D) models
      explain successfully a proximal-distal organization and movement of the motile
      cell. However, more adequate two-dimensional (2-D) models are lacking. We propose
      a multiscale 2-D computational model of the lamellipodium (motile appendage) of a
      simply shaped, rapidly crawling fish keratocyte cell. We couple submodels of (i)
      protrusion and adhesion at the leading edge, (ii) the elastic 2-D lamellipodial
      actin network, (iii) the actin-myosin contractile bundle at the rear edge, and
      (iv) the convection-reaction-diffusion actin transport on the free boundary
      lamellipodial domain. We simulate the combined model numerically using a finite
      element approach. The simulations reproduce observed cell shapes, forces, and
      movements and explain some experimental results on perturbations of the actin
      machinery. This novel 2-D model of the crawling cell makes testable predictions
      and posits questions to be answered by future modeling.

PMID- 19116674
TI  - [The essence of surgery - a unique relationship between science and art].

PMID- 19116675
TI  - [Cronos "versus" Zeus].

PMID- 19116673
TI  - Normalization of voltage-sensitive dye signal with functional activity measures.
AB  - In general, signal amplitude in optical imaging is normalized using the well
      established DeltaF/F method, where functional activity is divided by the total
      fluorescent light flux. This measure is used both directly, as a measure of
      population activity, and indirectly, to quantify spatial and spatiotemporal
      activity patterns. Despite its ubiquitous use, the stability and accuracy of this
      measure has not been validated for voltage-sensitive dye imaging of mammalian
      neocortex in vivo. In this report, we find that this normalization can introduce
      dynamic biases. In particular, the DeltaF/F is influenced by dye staining
      quality, and the ratio is also unstable over the course of experiments. As
      methods to record and analyze optical imaging signals become more precise, such
      biases can have an increasingly pernicious impact on the accuracy of findings,
      especially in the comparison of cytoarchitechtonic areas, in area-of-activation
      measurements, and in plasticity or developmental experiments. These dynamic
      biases of the DeltaF/F method may, to an extent, be mitigated by a novel method
      of normalization, DeltaF/DeltaF(epileptiform). This normalization uses as a
      reference the measured activity of epileptiform spikes elicited by global
      disinhibition with bicuculline methiodide. Since this normalization is based on a
      functional measure, i.e. the signal amplitude of "hypersynchronized" bursts of
      activity in the cortical network, it is less influenced by staining of non
      functional elements. We demonstrate that such a functional measure can better
      represent the amplitude of population mass action, and discuss alternative
      functional normalizations based on the amplitude of synchronized spontaneous
      sleep-like activity. These findings demonstrate that the traditional DeltaF/F
      normalization of voltage-sensitive dye signals can introduce pernicious
      inaccuracies in the quantification of neural population activity. They further
      suggest that normalization-independent metrics such as waveform propagation
      patterns, oscillations in single detectors, and phase relationships between
      detector pairs may better capture the biological information which is obtained by
      high-sensitivity imaging.

PMID- 19116676
TI  - [The cardiothoracic surgery resident].

PMID- 19116677
TI  - [Surgical management of pulmonary aspergilloma].
AB  - After formation of fungus ball in pre-existing cavities, antifungal agents are
      very hard to control the infection. Surgical resection offers the only realistic
      chance of a permanent cure for aspergilloma. However, surgical indications are
      still a controversy because of the high incidence of postoperative complications.
      The purpose of this study was to evaluate our indications and results in the
      surgical treatment of aspergilloma, focusing attention on the postoperative
      complications and risk factors. From 1990 to 2004, 60 patients with mean age of
      44.6 (range, 20-69) were submitted to pulmonary surgery for excision of
      aspergilloma. Forty-one patients (68.3%) were male, 25 patients (41.7%) were
      smokers and 47 (78.3%) had tuberculosis as the underlying lung disease. The most
      frequent indication for surgery was haemoptysis (88.3%). The cavities were mainly
      situated in the upper lobes (85.0%) and in the right lung (68.3%). Approximately
      half of aspergillomas (56.7%) were classified as complex aspergillomas. The
      procedures performed were : 7 pneumectomies (11.7%), 3 bilobectomies (5.0%), 42
      lobectomies (70.0%), 7 wedge resections (11.7%) and one cavernostomy (1.7%).
      There were 3 postoperative deaths (5%), and major complications occurred in 16.3%
      of the patients including: bleeding (n=3) and bronchopleural fistula (n=2).
      Recurrence rate was 3.3%. Surgical resection of pulmonary aspergilloma is
      effective in preventing recurrence of hemoptysis. Preoperative preparation of the
      patient, meticulous surgical technique, asn postoperative care reduced the rate
      of complications. We recommend early surgical resection of symptomatic cases with
      reasonable complications.

PMID- 19116678
TI  - [Kommerell diverticula associated with dysphagia: a clinical case and review of
      the literature].
AB  - We report the case of a young female with disphagia and weigth loss caused by a
      vascular ring associated with right aortic arch, Kommerell diverticula, and left
      retroesophageal ligamentum arteriosum (ductus arteriosus). The patient underwent
      surgical treatment. A left thoracotomy was performed. Surgical technique included
      diverticulum ressection and an aortopexia. There were no major complications. We
      also discuss the incidence, pathology, diagnosis, clinical features and treatment
      of this rare disease.

PMID- 19116679
TI  - [Carotid body tumors. A 10-years experience in the management of the disease].
AB  - INTRODUCTION: Carotid body tumours (CBT) are neoplasms that develop from
      paragangionic cells of this structure. They are rare, with an estimated incidence
      of 1:30000 and can be associated with other neuro-endocrine neoplasia. The
      authors report their experience in the management of the disease, in the last 10
      years. MATERIAL AND METHODS: Eight patients (with eight tumours) were treated,
      all submitted to tumour resection. 75% were female and the mean age was 56 years.
      We report a 12,5% incidence of neurological sequelae from surgery, and no
      mortality. In the follow-up (which varied between 1 and 10 years), no local or
      contralateral recurrence or metastasis were registered. Also, we did not found
      family cases of this disease. CONCLUSIONS: The authors noticed an unusually high
      proportion of female patients. The tumour resection was curative in all patients,
      with a rate of neurological complications inferior to that reported in other
      published series. These neurological sequelae were reported in patients with
      large tumours, thus reinforcing the outmost importance of an early diagnosis. Pre
      operative selective embolization of these tumours can be helpful in the resection
      of large tumours, allowing a potential reduction in neurological complications.

PMID- 19116680
TI  - [Femoro-distal revascularization surgery: 5-years retrospective analysis of
      results].
AB  - PURPOSE: We describe the outcomes of femoro-distal bypass procedures used to
      treat peripheral arterial occlusive disease (PAOD). The aim of this retrospective
      analysis was to evaluate primary patency and limb salvage at 5 years. METHODS AND
      PATIENTS: We retrospectively studied 122 consecutive patients who underwent
      femoro-distal bypass surgery from 1999 to 2002. Information was collected from
      clinical charts at S. Joao Hospital, Porto, Portugal. Kaplan-Meier curves were
      used to calculate primary patency and limb salvage rates; groups were compared
      using Cox proportional hazards models. RESULTS: Five-year cumulative primary
      patency was 67,1% and limb-salvage rate was 71,1%. Major amputation risk for
      diabetics was significantly higher - 49% - compared with 18% in non-diabetics
      patients (p=0,0001). There were trends associating major amputation with women
      and smokers; there were also trends associating hypertension and in situ
      saphenous vein bypass with lower risk of major amputation . CONCLUSION: Our
      preliminary results support the view that infrainguinal revascularization can be
      safely performed, with acceptable five-year cumulative primary patency and major
      amputation rates. The risk of major amputation, however, is significantly
      increased in diabetic patients.

PMID- 19116681
TI  - [Non-atherosclerotic lower limbs ischemia in young athletes].
AB  - Although rare, the iliac endofibrosis and the popliteal artery entrapment
      syndrome are undoubtfully recognised as causes of intermittent claudication in
      young patients, particularly in athletes. The authors report the clinical case of
      a young female athlete, with disabling claudication of the right lower limb due
      to a stenosis of the external iliac artery and a case of an acute ischemia in a
      male cyclist owing to an extrinsic compression of the popliteal artery by
      anomalous muscular bundles. Both cases underwent successful surgical management.
      The early suspicion and diagnosis of these situations is of utmost importance to
      prevent complications that may be particularly severe.

PMID- 19116682
TI  - [Germ cell tumor of the testis with invasion of inferior vena cava.
      Multidisciplinary surgical management].
AB  - The authors report the clinical case of a 34 years old male, with a germ cell
      tumor of the testis, who developed large retroperitoneal metastasis, with
      compression and later on invasion of the inferior vena cava. The patient
      underwent chemotherapy followed by resection of the original tumor and of the
      retroperitoneal metastasis and the vena cava was replaced by a vascular
      prosthesis. The post operative course was uneventful and one year later he was
      found in excellent condition. The rarity of the situation as well as of its
      surgical management justifies the presentation and the discussion of the case,
      based on the most recent data of the literature dedicated to the topic.

PMID- 19116683
TI  - [Critical appraise of systematic reviews in vascular surgery. A practical
      example].
AB  - Basic and clinical research are the basis for the advances in medicine. Nowadays
      we investigate everything (patients, diseases, health systems, outcomes,
      management, policies, etc.) and this research is reflected in a growing number of
      published medical articles, with millions of papers stored in the biomedical
      databases. There is the need to select, analyze and synthesize all this evidence,
      and making it available in a simple and timely fashion to the decision makers.
      One instrument to achieve this is the guidelines, another is the systematic
      reviews of the literature. Systematic reviews are research projects per si and
      constitute a very significant scientific advance, with clear implications in
      clinical care, scientific research and even policies, because they are
      integrative analytic instruments of the available information, allowing evidence
      based answers. Recently a Cochrane Library systematic review was published
      showing benefits of escin in chronic venous insufficiency. We appraise this study
      in terms of validity, importance and applicability as an example of critical
      appraisal of the scientific evidence.

PMID- 19116684
TI  - [Transfixive gunshot wound of the supraceliac aorta. Successful surgical
      management].

PMID- 19116685
TI  - Comparing evolutionary patterns and variability in the mitochondrial control
      region and cytochrome B in three species of baleen whales.
AB  - The rapidly evolving mitochondrial control region remains an important source of
      information on phylogeography and demographic history for cetaceans and other
      vertebrates, despite great uncertainty in the rate of nucleotide substitution
      across both nucleotide positions and lineages. Patterns of variation in linked
      markers with slower rates of evolution can potentially be used to calibrate the
      rate of nucleotide substitution in the control region and to better understand
      the interplay of evolutionary and demographic forces across the mitochondrial
      genome above and below the species level. We have examined patterns of diversity
      within and between three baleen whale species (gray, humpback, and Antarctic
      minke whales) in order to determine how patterns of molecular evolution differ
      between cytochrome b and the control region. Our results show that cytochrome b
      is less variable than expected given the diversity in the control region for gray
      and humpback whales, even after functional differences are taken into account,
      but more variable than expected for minke whales. Differences in the frequency
      distributions of polymorphic sites and in best-fit models of nucleotide
      substitution indicate that these patterns may be the result of hypervariability
      in the control region in gray and humpback whales but, in minke whales, may
      result from a large, stable or expanding population size coupled with saturation
      at the control region. Using paired cytochrome b and control region data across
      individuals, we show that the average rate of nucleotide substitution in the
      control region may be on average 2.6 times higher than phylogenetically derived
      estimates in cetaceans. These results highlight the complexity of making
      inferences from control region data alone and suggest that applying simple rules
      of DNA sequence analyses across species may be difficult.

PMID- 19116686
TI  - The complete nucleotide sequence and genome structure of potato latent virus.

PMID- 19116689
TI  - A suicidal DNA vaccine co-expressing two major membrane-associated proteins of
      porcine reproductive and respiratory syndrome virus antigens induce protective
      responses.
AB  - We constructed a suicidal DNA vaccine pSFV-ORF5m/ORF6 co-expressing GP5m (a
      modified GP5) and M proteins of porcine reproductive and respiratory syndrome
      virus (PRRSV). In mice immunization, specific immune responses were elicited by
      the suicidal DNA vaccine pSFV-ORF5m/ORF6. The immunogenicity and protective
      efficiency was then evaluated in piglets immunized with pSFV-ORF5m/ORF6 before
      virus challenge: PRRSV-specific neutralizing antibodies and lymphocyte
      proliferative responses were developed. Post-PRRSV challenge, these immune
      responses were further boosted and partial protection was obtained.

PMID- 19116690
TI  - Lentiviral vector-derived shRNAs confer enhanced suppression of Semliki forest
      virus replication in BHK-21 cells compared to shRNAs expressed from plasmids.
AB  - Semliki forest virus (SFV) is a pathogen causing lethal encephalitis in
      laboratory mice. In this study, we obtained three short hairpin RNAs (shRNAs)
      which could specifically target SFV sequence in GFP reporting systems and
      effectively suppress SFV replication in luciferase-containing reporter virus
      system. At a multiplicity of infection (MOI) of 0.001, the luciferase reporter
      activity was reduced by 78-92% by shRNA expression plasmids and virus yields
      reduced 2 to 10-fold at 20 h post-infection. When lentiviral vector-derived
      shRNAs were employed, the virus titers decreased 8 to 126-fold at 24 h post
      infection and 6 to 19-fold at 48 h post-infection and the cell survival was
      prolonged. These data formed the basis for further in vivo studies of RNA
      interference in mouse models.

PMID- 19116691
TI  - Squalene-hopene cyclase (Spterp25) from Streptomyces peucetius: sequence
      analysis, expression and functional characterization.
AB  - Squalene-hopene cyclase, which catalyzes the complex cyclization of squalene to
      the pentacyclic triterpene, hopene, is a key enzyme in the biosynthesis of
      hopanoids. The deduced amino acid sequence of the Streptomyces peucetius gene
      (spterp25) had significant similarity to other prokaryotic squalene-hopene
      cyclases. Like other triterpene cyclases, the S. peucetius squalene-hopene
      cyclase contains eight so-called QW-motifs with an aspartate-rich domain. The
      2,025-bp squalene-hopene cyclase-encoding gene was expressed in Escherichia coli
      BL21(DE3)pLySs, and the in vitro activity of the recombinant cyclase was
      demonstrated using purified membrane protein. The cyclization product hopene was
      identified by gas chromatography/mass spectrometry (GC/MS).

PMID- 19116692
TI  - Probiotic potential of lactic acid bacteria isolated from fermented dairy milks
      on antiproliferation of colon cancer cells.
AB  - Fifty-four strains of lactic acid bacteria obtained from fermented dairy milks
      were investigated for possible use as probiotics and for colon cancer biological
      products. Five of these strains inhibited growth of eight food-borne pathogens
      including Helicobacter pylori, Escherichia coli, and Salmonella typhimurium.
      Three of these strains survived at pH 2.5 and in 0.3% bile salts. Additionally
      they produced no haemolysis, were resistant to kanamycin and adhered to Caco-2
      cells. 16S rRNA gene sequences of probiotic strains indicated that RM11 and RM28
      were Enterococcus faecium and Lactobacillus fermentum, respectively. Both the
      cultured medium and live whole cells from probiotic strains were tested for
      antiproliferation of colon cancer cells through MTT and Trypan Blue exclusion
      assays. The probiotic strains of E. faecium RM11 and L. fermentum RM28 also
      triggered antiproliferation of colon cancer cells at the rates of 21-29%, and 22
      29%, respectively. This suggested that both strains could be used as potential
      probiotics in functional food or for colon cancer biological products.

PMID- 19116693
TI  - Time to "go large" on biofilm research: advantages of an omics approach.
AB  - In nature, the biofilm mode of life is of great importance in the cell cycle for
      many microorganisms. Perhaps because of biofilm complexity and variability, the
      characterization of a given microbial system, in terms of biofilm formation
      potential, structure and associated physiological activity, in a large-scale,
      standardized and systematic manner has been hindered by the absence of high
      throughput methods. This outlook is now starting to change as new methods
      involving the utilization of microtiter-plates and automated spectrophotometry
      and microscopy systems are being developed to perform large-scale testing of
      microbial biofilms. Here, we evaluate if the time is ripe to start an integrated
      omics approach, i.e., the generation and interrogation of large datasets, to
      biofilms--"biofomics". This omics approach would bring much needed insight into
      how biofilm formation ability is affected by a number of environmental,
      physiological and mutational factors and how these factors interplay between
      themselves in a standardized manner. This could then lead to the creation of a
      database where biofilm signatures are identified and interrogated. Nevertheless,
      and before embarking on such an enterprise, the selection of a versatile, robust,
      high-throughput biofilm growing device and of appropriate methods for biofilm
      analysis will have to be performed. Whether such device and analytical methods
      are already available, particularly for complex heterotrophic biofilms is,
      however, very debatable.

PMID- 19116694
TI  - Involvement of G-alpha protein GNA3 in production of cell wall-degrading enzymes
      by Trichoderma reesei (Hypocrea jecorina) during mycoparasitism against Pythium
      ultimum.
AB  - The involvement of the G-alpha protein GNA3 in the production of cell wall
      degrading enzymes (CWDEs) by Trichoderma reesei during antagonism against Pythium
      ultimum was investigated. cAMP content was 2.8-fold higher in the T. reesei
      mutant gna3QL than in the parental TU-6. The gna3QL, like TU-6, inhibited the
      growth of P. ultimum in dual culture assays. Scanning electron microscopy showed
      that the gna3QL promoted more morphological alterations of P. ultimum cell wall
      than TU-6. In general, gna3QL produced higher activities of CWDEs than TU-6. We
      therefore suggest that CWDEs production during mycoparasitism by T. reesei
      against P. ultimum may be associated with the level of GNA3 activity.

PMID- 19116695
TI  - Molecular engineering of the cellulosome complex for affinity and bioenergy
      applications.
AB  - The cellulosome complex has evolved to degrade plant cell walls and, as such,
      combines tenacious binding to cellulose with diverse catalytic activities against
      amorphous and crystalline cellulose. Cellulolytic microorganisms provide an
      extensive selection of domains; those with affinity for cellulose, cohesins and
      their dockerin binding partners that define cellulosome stoichiometry and
      architecture, and a range of catalytic activities against carbohydrates. These
      robust domains provide the building blocks for molecular design. This review
      examines how protein modules derived from the cellulosome have been incorporated
      into chimaeric proteins to provide biosynthetic tools for research and industry.
      These applications include affinity tags for protein purification, and non
      chemical methods for immobilisation and presentation of recombinant protein
      domains on cellulosic substrates. Cellulosomal architecture provides a paradigm
      for design of enzymatic complexes that synergistically combine multiple catalytic
      subunits to achieve higher specific activity than would be obtained using free
      enzymes. Multimeric enzymatic complexes may have industrial applications of
      relevance for an emerging carbon economy. Biocatalysis will lead to more
      efficient utilisation of renewable carbon-fixing energy sources with the added
      benefits of reducing chemical waste streams and reliance on petroleum.

PMID- 19116696
TI  - Pulmonary embolism and portal vein thrombosis in an immunocompetent adolescent
      with acute cytomegalovirus hepatitis.
AB  - Cytomegalovirus infection is usually asymptomatic or resembles infectious
      mononucleosis with fever, pharyngitis, arthralgias, lymphadenopathy, and atypical
      lymphocytosis. Even though primary CMV infection is usually self-limited in
      healthy individuals, significant complications can develop in immunocompromised
      patients. Venous or arterial thromboembolic phenomena are uncommon, yet very
      serious complications of CMV infection. Most published reports describe
      immunosupressed patients after organ transplantation or in the presence of HIV co
      infection. However, thrombotic events in CMV infected immunocompetent individuals
      may occur. We describe the case of an immunocompetent adolescent with acute
      cytomegalovirus hepatitis that was complicated with pulmonary embolism and portal
      vein thrombosis. To our knowledge, this is the first reported case in which these
      two thrombotic phenomena occurred simultaneously in an adolescent with no obvious
      predisposing factors for thrombosis in the setting of an acute CMV infection.

PMID- 19116697
TI  - Spanning the globe.

PMID- 19116698
TI  - Diffusion weighted imaging in heroin-associated spongiform leukoencephalopathy.
AB  - BACKGROUND: Heroin-associated spongiform leukoencephalopathy (HASL) is a rare
      complication of heroin abuse. We report a case that highlights the increased
      sensitivity of diffusion weighted imaging (DWI) compared with T2-weighted imaging
      in the acute setting of HASL. METHODS: Single case report. RESULTS: A 36-year-old
      male with a history of heroin abuse (snorting) presented with a 3-day history of
      lethargy. MRI brain revealed restricted diffusion involving the globus pallidum
      and cerebral cortex bilaterally that was not seen on fluid-attenuated inversion
      recovery (FLAIR) images. The patient was diagnosed with acute HASL. Repeated MRI
      FLAIR at 3 months confirmed the development of atrophy and T2 hyperintensity in
      the subcortical white matter, consistent with leukoencephalopathy. Neurological
      exam at 3-month follow-up was nonfocal. CONCLUSIONS: Restricted diffusion, which
      likely corresponds to electron microscopic findings of fluid entrapment between
      the myelin lamellae, may be detectable earlier than changes on FLAIR. Clinicians
      should be aware of the neuroimaging findings of HASL and the increased
      sensitivity of MRI DWI over T2-weighted images in detecting HASL acutely.

PMID- 19116699
TI  - Relationship between hemoglobin concentrations and outcomes across subgroups of
      patients with aneurysmal subarachnoid hemorrhage.
AB  - OBJECTIVE: Anemia predicts poor outcome following aneurysmal subarachnoid
      hemorrhage (SAH). We hypothesized that this association would be stronger among
      patients with more severe SAH, since these patients are likely to be more
      vulnerable to secondary brain injury in the form of reduced cerebral oxygen
      delivery. METHODS: Daily nadir hemoglobin (Hb) concentrations over 2 weeks
      following SAH were retrieved in 245 consecutive patients, and compared between
      those with a favorable versus unfavorable outcome. The analysis was repeated with
      patients dichotomized as follows: WFNS score 4-5 vs. 1-3; modified Fisher score
      (MFS) 4 vs. 0-3; and vasospasm present vs. absent. Mixed effect models and
      multivariable analysis using the generalized estimating equation were employed to
      assess correlated data with repeated measures. RESULTS: Patients with an
      unfavorable outcome consistently had lower Hb concentrations, especially between
      days 6-11 following SAH (P ranging from <0.001 to 0.009), as well as a greater
      fall in Hb over time (beta = -0.07, P < 0.001). This was true regardless of WFNS
      score, MFS, or the presence or absence of vasospasm. However, the effect was
      somewhat more pronounced among patients with higher WFNS and modified Fisher
      scores. CONCLUSION: Lower Hb levels are associated with worse outcomes regardless
      of SAH severity or the development of vasospasm. This finding may imply that a
      lower Hb concentration is largely a marker for a greater degree of systemic
      illness, rather than necessarily causing direct harm. However, the association is
      somewhat stronger among patients with more severe SAH. Thus, if there is a
      benefit for maintaining higher Hb levels with transfusions or erythropoietin, it
      may be more pronounced among these patients.

PMID- 19116700
TI  - Safety of imipenem/cilastatin in neurocritical care patients.
AB  - BACKGROUND: Infection in the intensive care unit (ICU) empirically requires broad
      spectrum antibiotics. Imipenem/cilastatin, often reserved for more serious
      hospital-acquired infections, is thought to be associated with a higher risk of
      seizures than other penicillins and carbapenems. We sought to evaluate the safety
      of imipenem/cilastatin in the treatment of infections, including meningitis, in
      neurocritical care patients. METHODS: Pertinent literature was identified through
      MEDLINE (1966-2007) using search terms imipenem, seizure, carbapenem, and
      meropenem. A review of the literature is presented. RESULTS: Carbapenem
      antibiotics remain active against most Gram-positive and Gram-negative organisms,
      and are often used in critically ill patients. Drug-induced seizures are a rare
      but serious adverse effect, with carbapenems being one of the most common classes
      of antibiotics associated with seizures. Seizure rates in patients treated with
      imipenem/cilastatin and meropenem are similar. One small pediatric study of 21
      patients showed a high incidence of seizures and is often cited as the reason
      imipenem should not be used in meningitis. However, many studies noting seizures
      with both meropenem and imipenem/cilastatin attribute this to patients with lower
      body weight, elderly, or those with impaired renal function. CONCLUSIONS: When
      dosed appropriately, imipenem/cilastatin may be used to treat serious infections
      in critically ill patients with central nervous system (CNS) disorders or injury
      with minimal seizure risk. Imipenem/cilastatin safety data is lacking for
      meningitis and cautious use is warranted.

PMID- 19116702
TI  - [With good scores in the next 120 years!].

PMID- 19116703
TI  - [30th year of the Ethics Commission of the Medical University of Vienna:
      guarantee for integrity and transparent research].

PMID- 19116704
TI  - [Finding the right words for medical decisions at life's end].

PMID- 19116706
TI  - A case with giant arachnoid cysts manifested as migraine.

PMID- 19116705
TI  - [Medical ethics teaching].
AB  - In most European countries, medical ethics has become a more or less established
      subject in medical school curricula. Accordingly, the need to evaluate its
      success has arisen. In our paper, we describe the controversial debate about the
      proper goals of teaching medical ethics. Secondly, we present an overview of
      current efforts to measure and evaluate the outcome and effect of different
      medical ethics teaching programmes on medical students and young physicians. We
      conclude that medical ethics teaching is amenable to a great variety of teaching
      and evaluation methods. Finally, we argue that medical ethics teaching should
      include: (1) the teaching of moral reasoning skills, (2) the instruction about
      relevant ethical knowledge, as well as (3) the development of certain character
      traits. Methods to evaluate ethical knowledge and moral reasoning skills are
      readily available, while the evaluation of the development of character traits
      poses important conceptual difficulties.

PMID- 19116707
TI  - Prevalence of human papillomavirus types 6, 11, 16 and 18 in young Austrian women
      - baseline data of a phase III vaccine trial.
AB  - INTRODUCTION: Cervical cancer is the second most common cancer among women
      worldwide. In the absence of changing risk or intervention, it is projected that
      in comparison with 2002 there will be a 40% increase in the number of new cases
      of cervical cancer by 2020. HPV types 16 and 18 cause 70% of cervical cancers
      worldwide, 50% of high-grade cervical intraepithelial neoplasias and 25% of low
      grade neoplasias. HPV types 6 and 11 are the causative agent of > 90% of genital
      warts. The aim of this study was to assess the baseline prevalence of infection
      with HPV 6, 11, 16 and 18 in young Austrian women. METHODS: Austrian females aged
      16-24 (n = 123) were enrolled in a double-blind, placebo-controlled, randomized
      phase III trial of a quadrivalent HPV (types 6, 11, 16, 18) vaccine (FUTURE I,
      ClinicalTrials.gov number NCT00092521). Healthy women who were not pregnant and
      had no prior history of genital warts or abnormal results on cervical cytologic
      testing and had fewer than five lifetime sex partners were eligible for
      enrollment. The study sub-population was recruited primarily from university
      settings. RESULTS: Analysis of the sexual history of the Austrian subjects showed
      that 92.7% (114/123) were non-virgins and 46.3% were current smokers. At
      enrollment, 15 (13.5%) had positive serological or PCR tests for HPV 6, 11, 16 or
      18. Serologically, 14 (12.3%) of women were positive to HPV 6, 11, 16 or 18: of
      these, 13 (11.4%) were positive for HPV 16, four (3.5%) were positive for HPV 18,
      and one (0.9%) for HPV 6. By PCR all were negative for HPV 6 and 11, whereas
      seven (6.1%) were positive for HPV 16 and one (0.9%) for HPV 18. Abnormal
      cytology was observed in 12 (10.3%) women. DISCUSSION: Although the prevalence of
      vaccine HPV types among young Austrian women with fewer than five lifetime sexual
      partners was lower than in international data, we observed a high prevalence of
      abnormal cytology and smoking. These data suggest that a substantial number of
      Austrian women are at risk for HPV-related disease.

PMID- 19116708
TI  - Relevance of short-term variation of B-type natriuretic peptide in patients with
      clinically stable heart failure.
AB  - BACKGROUND: In patients with clinically stable chronic heart failure, circulating
      B-type natriuretic peptide (BNP) levels may exhibit considerable variation over a
      period of a few days. The aim of this study was to evaluate the clinical impact
      of this phenomenon. METHODS: In 23 patients with clinically stable mild-to
      moderate systolic heart failure [median (interquartile range) 72 (64-77) years,
      left ventricular ejection fraction 30 (27-40)%] and a history of previous
      hospitalization for heart failure, BNP was measured at two time points [T1 and
      T2, interval 5 (3-7) days] for calculation of the absolute change in BNP
      concentrations between T1 and T2 (DeltaBNP; irrespective of whether there was a
      decrease or increase). Follow-up for rehospitalization was 436 (407-458) days.
      RESULTS: In the group overall, DeltaBNP was 26 (9-116) pg/ml [19 (10-28)% of the
      value at T1]. During follow-up, 8/23 (35%) patients were rehospitalized. BNP
      concentrations at T1 [340 (187-533) vs. 210 (108-606) pg/ml; P = 0.33] and T2
      [328 (125-491) vs. 259 (89-536) pg/ml; P = 0.51] were similar in patients who
      were rehospitalized and those who were not; however, DeltaBNP was higher in
      patients requiring rehospitalization [98 (36-186) vs. 19 (6-93) pg/ml; P = 0.04].
      Patients with DeltaBNP <26 pg/ml had a longer rehospitalization-free survival
      than those with DeltaBNP > or = 26 pg/ml (log rank P = 0.02). Sensitivity and
      specificity of DeltaBNP > or = 26 pg/ml for the prediction of rehospitalization
      were 88% and 67% respectively. CONCLUSIONS: In this small study among patients
      with clinically stable heart failure, higher DeltaBNP over a period of a few days
      was associated with a higher likelihood of rehospitalization during follow-up.

PMID- 19116709
TI  - [Efficacy of glycopyrronium bromide and scopolamine hydrobromide in patients with
      death rattle: a randomized controlled study].
AB  - BACKGROUND: Death rattle is an extremely distressing symptom for the dying
      patient and for his environment. The aim of this study was to assess the efficacy
      of glycopyrronium bromide as compared with scopolamine hydrobromide in
      alleviating death rattle in terminal cancer patients with cognitive impairment.
      METHODS: In a randomized, controlled study design patients were allocated in two
      groups. Group A received scopolamine hydrobromide in a dose of 0.5 mg
      intravenously every 6 hours for a period of 12 hours, group B received
      glycopyrronium bromide 0.4 mg every 6 hours for a period of 12 hours. In
      addition, standardized sedatives were administered as required and the analgesic
      therapy continued either orally or, if necessary, subcutaneously or intravenously
      in equipotent doses. Every 2 hours death rattle was assessed and rated on a scale
      of 1 to 5 (1 = audible breathing noises, 5 = very severe rattling noises). In
      addition, restlessness and expressions of pain were assessed and rated on a scale
      of 1 to 3 (1 = mild, 2 = moderate, 3 = severe). RESULTS: 13 patients were
      included in the study, 7 patients were allocated to group A and 6 patients to
      group B. There were no significant differences in demographic data, age, weight
      and diagnosis distribution between the two groups. Group B demonstrated a
      significant reduction of death rattle in the first 12 hours (p = 0.029) in
      comparison to group A. There were no significant differences concerning the side
      effects (restlessness, expressions of pain) in both groups. CONCLUSION:
      Glycopyrronium bromide given in a dose of 0,4 mg every six hours demonstrated a
      significant reduction of death rattle compared to scopolamine hydrobromide.
      Concerning side effects (restlessness, expressions of pain) there was no
      difference between both substances.

PMID- 19116710
TI  - Differences in risk factors for coronary heart disease in patients from
      continental and Mediterranean regions of Croatia.
AB  - BACKGROUND: There are few data on differences in exposure to risk factors for
      coronary heart disease (CHD) in relation to geographic areas, especially areas
      with large differences in terms of continental and Mediterranean climates. To
      study these differences in Croatia, we analyzed data from the Treatment and
      Secondary Prevention of Ischemic Coronary Events in Croatia V (TASPIC-CRO V)
      study, which recruited Croatian CHD patients in two principal regions
      (Mediterranean and continental) of the country. METHODS: A total of 31 Croatian
      research centers participated in the study. We collected information on personal
      details, demographic characteristics and risk factor exposure from the hospital
      medical records of 3054 CHD patients. Risk factors included history of cigarette
      smoking, hypertension, hyperlipidemia (total cholesterol, triglycerides, HDL
      cholesterol and LDL-cholesterol) and diabetes type 2. RESULTS: Both univariate
      and multivariate analyses showed that the prevalence of hypertension in examined
      CHD patients was significantly higher in the continental part of Croatia than in
      the Mediterranean part (univariate analysis: P < 0.001; multivariate analysis: P
      = 0.003). Multivariate analysis revealed a higher prevalence of decreased HDL
      cholesterol in continental Croatia (P = 0.006) and a higher prevalence of smokers
      in coastal Mediterranean Croatia (P = 0.007). A significant difference in total
      cholesterol levels was noted between hospitalized CHD patients in two
      Mediterranean subregions (P < 0.001). No significant differences between
      continental and coastal Mediterranean parts of Croatia were found for other CHD
      risk factors. CONCLUSIONS: Higher prevalences of both hypertension and decreased
      HDL-cholesterol were recorded in hospitalized CHD patients in the continental
      part of Croatia, but in coastal Mediterranean Croatia there was higher prevalence
      of smokers. Differences in total cholesterol, LDL-cholesterol and triglycerides
      between hospitalized CHD patients in continental and coastal Mediterranean
      Croatia did not follow the expected continental-Mediterranean pattern.

PMID- 19116711
TI  - Unilateral face swelling as first manifestation of metastatic pancreatic cancer:
      case report and review of the literature.
AB  - OBJECTIVE: Metastasis to the jaw is a rare finding in pancreatic cancer; only
      five cases of tumor spread to the oral region have been described. CASE REPORT:
      We report on a previously healthy 54-year-old man who attended the hospital in
      2006 because of a mandibular mass. Histology was positive for adenocarcinoma and
      computed tomography led to the diagnosis of pancreatic cancer. Chemoradiotherapy
      was started but had to be stopped early because of intraoral bleeding from the
      metastasis. The patient subsequently received palliative chemotherapy. The
      primary cancer was stabilized but the mandibular mass progressed despite
      cytostatic therapy. Despite best supportive measures the patient died nine months
      after presentation. CONCLUSION: In making the decision on whether metastasectomy
      should be performed in an uncommon site of metastatic spread such as the
      mandibula, both the possibility of cure and also the potentially decreased
      response to conservative therapy and the patient's decreased quality of life have
      to be considered.

PMID- 19116713
TI  - Tick-borne encephalitis virus - a rare cause of encephalitis in infants.

PMID- 19116712
TI  - Diagnostic algorithms, monitoring, prognostication, and therapy in chronic
      myeloid leukemia (CML): a proposal of the Austrian CML platform.
AB  - Chronic myeloid leukemia (CML) is a stem cell disease characterized by the
      BCR/ABL oncoprotein. The ABL kinase inhibitor imatinib is effective in most
      patients and considered standard first-line therapy. However, not all patients
      show a long-lasting response to this drug. In fact, resistance against imatinib
      has been described and is an emerging clinical problem in CML. For these
      patients, novel multi-kinase inhibitors such as nilotinib or dasatinib as well as
      stem cell transplantation, represent alternative treatment options. The decision
      concerning second-line therapies and selection of drugs is usually based on the
      presence and type of BCR/ABL mutations, the phase of disease, other disease
      related factors as well as patient-related factors including age, co-morbidity,
      and pharmacologic determinants. The current article provides an overview on
      diagnostic and therapeutic strategies for patients with treatment-naive and
      imatinib-resistant CML, together with proposed algorithms that were discussed and
      approved by members of the CML platform of the Austrian Society for Hematology
      and Oncology (OGHO) in 2007 and 2008. The resulting recommendations should assist
      in diagnosis and prognostication in CML, follow-up and disease-monitoring,
      patient selection for interventional therapies, and in the preparation and
      conduct of clinical trials.

PMID- 19116715
TI  - Rituximab-based therapy for gemcitabine-induced hemolytic uremic syndrome in a
      patient with metastatic pancreatic adenocarcinoma: a case report.
AB  - PURPOSE: The purpose of this report is to describe the management and outcome of
      an unusual complication of a commonly used chemotherapeutic agent. Gemcitabine is
      a known risk factor for hemolytic uremic syndrome (HUS), which can often have a
      rapidly fatal clinical course despite intervention with steroids, plasmapheresis
      and hemodialysis. METHODS: A retrospective report of the first case of
      gemcitabine-related HUS, in a patient with metastatic pancreatic adenocarcinoma,
      treated with a variety of standard therapies in addition to rituximab is
      presented. The hematologic response parameters and clinical outcomes to each of
      the therapies given are described. RESULTS: Chemotherapy-induced HUS was
      aggressively treated with plasmapheresis, high-dose steroids, vincristine and
      rituximab. Platelet recovery and clinical improvement coincided with
      administration of rituximab. In addition, aggressive supportive measures to
      manage renal failure (hemodialysis) and labile hypertension, allowed this patient
      to have an extended survival as a result of successful therapy for this
      complication despite an underlying rapidly fatal malignancy. CONCLUSION: This
      case highlights the importance of timely application of aggressive measures even
      in patients with known diagnosis of a fatal malignancy as these interventions can
      prolong life and be of palliative benefit.

PMID- 19116716
TI  - Identification of potential marker genes for Trichoderma harzianum strains with
      high antagonistic potential against Rhizoctonia solani by a rapid subtraction
      hybridization approach.
AB  - A rapid subtraction hybridization approach was used to isolate genes
      differentially expressed during mycelial contact between Trichoderma harzianum
      (Hypocrea lixii) and Rhizoctonia solani, and could serve as marker genes for
      selection of superior biocontrol strains. Putatively positive clones were
      evaluated by transcription analysis during mycelial contact with R. solani versus
      growth on glucose, and for their differential transcription between two strains
      with either strong or poor biocontrol capability before, at, and after contact
      with R. solani. Besides four clones, which had similarity to putative but as yet
      uncharacterized proteins, they comprised ribosomal proteins, proteins involved in
      transcriptional switch and regulation, amino acid and energy catabolism,
      multidrug resistance, and degradation of proteins and glucans. Transcription of
      three clones was evaluated in five T. harzianum strains under confrontation
      conditions with R. solani. Two clones-acetyl-xylane esterase AXE1 and
      endoglucanase Cel61b-showed significant upregulation during in vivo confrontation
      of a T. harzianum strain that successively demonstrated a very high antagonistic
      capability towards R. solani, while expression was progressively lower in a
      series of T. harzianum strains with intermediate to poor antagonistic activity.
      These clones are promising candidates for use as markers in the screening of
      improved T. harzianum biocontrol strains.

PMID- 19116717
TI  - Adrenomedullin inhibits MAPK pathway-dependent rheumatoid synovial fibroblast
      mediated osteoclastogenesis by IL-1 and TNF-alpha.
AB  - The objective of this study is to determine the effects of adrenomedullin (AM) on
      IL-1- and TNF-alpha-induced rheumatoid synovial fibroblasts (RASFs)-mediated
      osteoclastogenesis. The formation of osteoclasts in co-cultures of RASFs and
      peripheral blood mononuclear cells was evaluated by tartrate-resistant acid
      phosphatase and resorption pit formation assay. The expression of RANKL, OPG, p
      ERK, p-p38, and p-JNK was examined by immunoblotting and quantitative reverse
      transcription-polymerase chain reaction. AM (1-52) inhibits IL-1- and TNF-alpha
      induced RASFs-mediated osteoclastogenesis. AM affected IL-1-, TNF-alpha-induced
      RANKL and OPG expression in RASFs. AM also inhibits IL-1 and TNF-alpha-induced
      phosphorylation of ERK-1/2, p38 MAPK, and JNK. Inhibitor of AM (AM 22-52)
      inhibits the effects of AM on the osteoclastogenesis. These results suggest that
      AM might be involved in the inflammatory cytokines-mediated osteoclastogenesis
      and thus bone damage, and indicate that it can be a new therapeutic strategy
      against joint destruction in RA.

PMID- 19116718
TI  - Lung parenchymal consolidation as an uncommon presentation and cause of delayed
      diagnosis in atypical Kawasaki syndrome.
AB  - We report three patients who initially showed prolonged fever, lung parenchymal
      consolidation and laboratory findings of pneumonia, and secondarily presented a
      clinical picture ascribed to Kawasaki syndrome. Two of these children developed
      coronary artery dilations, which regressed upon echocardiography after 12 months.
      In the case of infants showing broncho-pulmonary abnormalities with slow
      resolution, active inflammatory parameters and high fever persistence,
      pediatricians should consider atypical Kawasaki syndrome as a possible
      alternative diagnosis.

PMID- 19116719
TI  - Potential biomarkers for detecting pulmonary arterial hypertension in patients
      with systemic sclerosis.
AB  - Pulmonary arterial hypertension (PAH) is the major complication of systemic
      sclerosis (SSc) and the main cause of morbi-mortality. It is important to find
      predictors for this vascular problem. The objective of this study was to
      determine the serum levels of different biomarkers in patients with SSc and
      secondary PAH and to compare them with those of healthy control subjects to
      define their potential role as predictors of PAH. Cross-section study in which 20
      patients with SSc were included. PAH was diagnosed by echocardiogram. The optical
      densities of endoglin (Eng), endothelin-1 (ET-1), platelet-derived growth factor
      (PDGF), tumoral necrosis factor alpha (TNF-alpha), Transforming growth factor
      beta 2 (TGF-beta2) and Interleukin 8 (IL-8) were measured in 20 patients with SSc
      and 20 healthy controls matched by sex. The differences found between the group
      of patients with PAH and the control group were (mean or median and range): ET-1
      (0.20; 0.10-0.35 vs. 0.16; 0.10-0.24; P = 0.0276), IL-8 (195.7; 45.5-504 vs.
      118.9; 23-299.5; P = 0.0364), TNF-alpha (0.70; 0.50-0.96 vs. 0.48; 0.38-0.65; P =
      1 x 10(-8)) and Eng (0.95; 0.57-1.72 vs. 0.75; 0.57-0.89; P = 0.0028). A
      correlation was found between the progression of the disease and the development
      of Raynaud's phenomenon (Rho: 0.67 and P = 0.0011), ET-1 and Eng (Rho: 0.53 and P
      = 0.0196), and between IL-8 and Eng (Rho: 0.68 and P = 0.0019). In conclusions,
      the elevation of the serum levels of Eng and ET-1 could represent a useful tool
      as PAH biomarkers. Nevertheless, the diagnostic value of these markers needs to
      be determined by prospective studies.

PMID- 19116720
TI  - Functional characterization of a stilbene synthase gene using a transient
      expression system in planta.
AB  - The expression and functionality of a resveratrol synthase (RS) gene from peanut
      (Arachis hypogaea) was studied using an Agrobacterium tumefaciens-mediated
      transient expression system in Nicotiana benthamiana leaves. Functional analysis
      of RS was demonstrated by tracking its expression during 96 h. To measure the
      transcripts levels of RS transgene, real-time qRT-PCR was used and revealed that
      the highest level of transcripts was at 48 h post-transfection. Western blot
      analyses showed that RS protein was accumulated to the highest levels at 72 h
      post-transfection. Finally, HPLC and mass spectrometry analyses revealed the
      production of trans-piceid (resveratrol glucoside) as the major stilbenoid
      compound confirming the functional activity of the RS enzyme in planta. No
      activity of RS transgene was detected in negative controls. This strategy showed
      advantages over conventional systems because it does not require establishment of
      cell cultures, feeding with appropriate substrates or generation of stable
      transgenic plants. This transient system proved to be a rapid and direct approach
      to perform functional analysis of stilbene synthases, such as resveratrol
      synthase. Furthermore, this approach can be useful to study the metabolic effects
      of over-expressing or silencing specific genes within a short period of time.

PMID- 19116721
TI  - Enrollment in mental health courts: voluntariness, knowingness, and adjudicative
      competence.
AB  - Mental health courts (MHCs) are rapidly expanding as a form of diversion from
      jails and prisons for persons with mental illness charged with crimes. Although
      intended to be voluntary, little is known about this aspect of the courts. We
      examined perceptions of voluntariness, and levels of knowingness and legal
      competence among 200 newly enrolled clients of MHCs at two courts. Although most
      clients claimed to have chosen to enroll, at the same time, most claimed not to
      have been told the court was voluntary or told of the requirements prior to
      entering. The majority knew the "basics" of the courts, but fewer knew more
      nuanced information. A minority also were found to have impairments in legal
      competence. Implications are discussed.

PMID- 19116722
TI  - Shifting to first-line regimen after previous failure of irinotecan and
      oxaliplatin containing chemotherapies in unresectable metastatic colorectal
      cancer: a retrospective study of case analysis.
AB  - PURPOSE: Conventional use of FOLFIRI-FOLFOX or the reverse sequence is the
      optional regimen in metastatic unresectable colorectal cancer (CRC). We present
      our experience in chemotherapy (C/T) shifting to first-line regimen after
      previous failure of irinotecan and oxaliplatin containing regimens. MATERIALS AND
      METHODS: A total of 48 patients with metastatic unresectable CRC were examined
      retrospectively. All the patients had both failure of a first-line C/T and a
      second-line C/T. Of these patients, 13 patients received C/T shifting to first
      line regimen. Data were collected retrospectively. RESULTS: Rate of disease
      control of 38.4% was achieved (five in 13 patients). In the positive disease
      control group, metastatic sites were all extra-hepatic (five patients). In the
      negative disease control group, hepatic metastatic rate was 62.5% (five in eight
      patients, P=0.044). CONCLUSIONS: Even after previous failure of irinotecan and
      oxaliplatin containing C/T, we observe positive disease control response and
      survival benefit in selected patients with C/T shifting to the first-line regimen
      especially in extra-hepatic metastasis. The preliminary results are proposed to
      gain insight into the need for further investigations and large-scale studies.

PMID- 19116724
TI  - What happens when vacuum extraction fails?
AB  - OBJECTIVE: To compare maternal and neonatal outcomes of forceps delivery or
      cesarean section (CS) following failed vacuum extraction. METHODS: A
      retrospective cohort study of all women who underwent forceps delivery and/or CS
      after failed vacuum extraction in 1993-2006 was conducted. Cases were identified
      by searching the computerized delivery discharge database. All files were
      reviewed and those who underwent CS were compared to those who underwent forceps
      delivery. RESULTS: Compared to CS (n = 112), forceps delivery (n = 328) was
      associated with a significantly higher risk of adverse composite maternal outcome
      (P = 0.001), third/fourth-degree perineal tears (P = 0.005), prolonged
      hospitalization (P = 0.03), and cephalohematoma (P = 0.04). In the forceps group,
      the risk was increased by nulliparity, occipito-posterior position, S + 1
      station, and pre-pregnancy maternal obesity; in the cesarean group, higher
      maternal risk was associated with delivery in the evening/night and S + 2 or
      lower. In cases of nonreassuring fetal heart rate, composite neonatal outcome was
      worse after CS. CONCLUSION: Forceps delivery after failed vacuum extraction may
      be associated with greater short-term maternal morbidity than CS, although it
      might be associated with better perinatal outcome in cases of nonreassuring fetal
      heart rate.

PMID- 19116725
TI  - Association of chemokines receptor (CCR5 Delta32) in idiopathic recurrent
      miscarriages among north Indians.
AB  - PURPOSE: Human reproduction is a complex process involving multiple factors for
      the success of pregnancy. Chemokines are one of the immunomodulators which may
      determine pregnancy outcome. In the present study, we have tested genetic
      association between CCR5 Delta32 polymorphism and idiopathic recurrent
      miscarriages (IRM) among north Indians. METHODS: Two hundred patients and 300
      age, sex and ethnically matched controls were genotyped for CCR5 Delta32
      polymorphism, genotype and allele frequencies were compared in both the groups.
      RESULTS: IRM patients had a three times higher (5.5 vs. 1.7%) frequency of
      heterozygote genotype (P = 0.0335, OR = 3.43; 95% CI = 1.17-10.04). Allele
      frequency in IRM patients was 3.7 and 0.83% among controls and the differences
      were statistically significant (P = 0.0349, OR = 3.37; 95% CI = 1.16-9.76).
      CONCLUSIONS: Our results demonstrated that it had a higher frequency of CCR5
      Delta32 at allelic level suggesting a possible susceptibility trend (OR = 3.43)
      and CCR5 Delta32 may be a potential genetic risk factor for IRM.

PMID- 19116726
TI  - Clinical management and immunohistochemical analysis of umbilical endometriosis.
AB  - PURPOSE: To established a strategy for diagnostic and therapeutic management of
      umbilical endometriosis and to determine the biological character. METHODS:
      Clinical examination, vaginal and abdominal ultrasound, magnetic resonance
      imaging of the abdominal wall and laparoscopy were performed on a 42-year-old
      woman with umbilical endometriosis. Surgery with umbilical reconstruction was
      performed by a new plastic surgery technique. Immunohistochemical analyses
      (against Ki 67, estrogen/progestogen receptor, CD10, smooth muscle actin, desmin,
      caldesmon, von Willebrandt factor, cyclooxygensae-2 and VEGF) were done to
      characterize the umbilical endometriotic lesion. RESULTS: The extension of the
      endometriotic lesion necessitated total removal of the umbilicus. Umbilical
      reconstruction was performed by a new plastic surgery technique. The lesion did
      express CD10, estrogen and progestogen receptors, and did show a moderate
      proliferation rate. Furthermore, signs of metaplastic processes such as smooth
      muscle metaplasia and angiogenesis were detected. The endometriotic lesion was
      positive not only for smooth muscle actin, caldesmon and desmin, but also for COX
      2 and VEGF. CONCLUSION: Based on a case report and a literature review, we
      discuss the diagnostic and therapeutic management of umbilical endometriosis at
      our endometriosis research center. Furthermore, our data suggest that the
      umbilical endometriotic lesion originated from reactivated multipotent cells.

PMID- 19116727
TI  - Accuracy of frozen section diagnosis in ovarian masses: experience at a tertiary
      oncology center.
AB  - PURPOSE: Accurate frozen section diagnosis is necessary for appropriate surgical
      management. In this study, we planned to determine the accuracy of frozen section
      diagnosis in our center and to study the factors which may influence the accuracy
      of frozen section diagnosis of ovarian tumors. METHODS: In the present study,
      frozen section diagnosis of adnexal masses in 282 patients was compared with
      permanent section diagnosis as the gold standard. RESULTS: The overall accuracy
      of frozen section diagnosis was 95.7%. The sensitivity of frozen section
      diagnosis for benign, borderline and malignant lesions was 99, 60, and 92%,
      respectively. The tumor size in discrepant cases was larger than the concordant
      cases, however no association between mucinous histology and inaccurate diagnosis
      was found. The sensitivities of gross examination and clinical data in
      distinguishing benign from non-benign lesions were 93 and 70%, respectively.
      CONCLUSION: Frozen section is a reliable method for surgical management of
      patients with adnexal masses. Gross examination and clinical data are two
      valuable parts of intraoperative consultation.

PMID- 19116728
TI  - An anionic class III peroxidase from zucchini may regulate hypocotyl elongation
      through its auxin oxidase activity.
AB  - The high number of peroxidase genes explains the description of numerous
      physiological functions and the fact that the in planta function of a single
      isoform has never been characterized yet. We analyzed in transgenic Arabidopsis
      thaliana the localization of a zucchini isoperoxidase (APRX), previously purified
      thanks to its pectin binding ability. We confirmed that the protein is localized
      near the cell wall, mainly produced in the elongation area of the hypocotyls and
      respond to exogenous auxin. In addition, the ectopic overexpression of APRX
      induced changes in growth pattern and a significant reduction of endogenous
      indole-3-acetic acid (IAA) level. In agreement with these observations APRX
      showed an elevated in vitro auxin oxidase activity. We propose that APRX
      participates in the negative feedback regulation of auxin level and consequently
      terminates the hypocotyl elongation process.

PMID- 19116730
TI  - Prairie dog alarm calls encode labels about predator colors.
AB  - Some animals have the cognitive capacity to differentiate between different
      species of predators and generate different alarm calls in response. However, the
      presence of any addition information that might be encoded into alarm calls has
      been largely unexplored. In the present study, three similar-sized human females
      walked through a Gunnison's prairie dog (Cynomys gunnisoni) colony wearing each
      of three different-colored shirts: blue, green, and yellow. We recorded the alarm
      calls and used discriminant function analysis to assess whether the calls for the
      different-colored shirts were significantly different. The results showed that
      the alarm calls for the blue and the yellow shirts were significantly different,
      but the green shirt calls were not significantly different from the calls for the
      yellow shirt. The colors that were detected, with corresponding encoding into
      alarm calls, reflect the visual perceptual abilities of the prairie dogs. This
      study suggests that prairie dogs are able to incorporate labels about the
      individual characteristics of predators into their alarm calls, and that the
      complexity of information contained in animal alarm calls may be greater than has
      been previously believed.

PMID- 19116729
TI  - Non-random X chromosome inactivation in Aicardi syndrome.
AB  - Most females have random X-chromosome inactivation (XCI), defined as an equal
      likelihood for inactivation of the maternally- or paternally-derived X chromosome
      in each cell. Several X-linked disorders have been associated with a higher
      prevalence of non-random XCI patterns, but previous studies on XCI patterns in
      Aicardi syndrome were limited by small numbers and older methodologies, and have
      yielded conflicting results. We studied XCI patterns in DNA extracted from
      peripheral blood leukocytes of 35 girls with typical Aicardi syndrome (AIC) from
      0.25 to 16.42 years of age, using the human androgen receptor assay. Data on 33
      informative samples showed non-random XCI in 11 (33%), defined as a >80:20%
      skewed ratio of one versus the other X chromosome being active. In six (18%) of
      these, there was a >95:5% extremely skewed ratio of one versus the other X
      chromosome being active. XCI patterns on maternal samples were not excessively
      skewed. The prevalence of non-random XCI in Aicardi syndrome is significantly
      different from that in the general population (p < 0.0001) and provides
      additional support for the hypothesis that Aicardi syndrome is an X-linked
      disorder. We also investigated the correlation between X-inactivation patterns
      and clinical severity and found that non-random XCI is associated with a high
      neurological composite severity score. Conversely, a statistically significant
      association was found between random XCI and the skeletal composite score.
      Correlations between X-inactivation patterns and individual features were made
      and we found a significant association between vertebral anomalies and random
      XCI.

PMID- 19116731
TI  - Natural DOM affects copper speciation and bioavailability to bacteria and
      ciliate.
AB  - This study aimed to investigate the influence of natural dissolved organic
      materials (DOM) on copper speciation (total dissolved, particulate, and free Cu2+
      ions) and bioavailability during a two-level experimental microbial food chain.
      Bacteria were used as the first trophic level, and Paramecium caudatum
      (protozoan) as the second. The organisms were obtained from a freshwater
      reservoir and kept under controlled laboratory conditions. Three experimental
      treatments were performed: exposure of the organisms to copper in the absence of
      DOM, exposure to DOM in the absence of copper, and exposure to both copper and
      DOM. Freshwater medium containing natural DOM and copper at a total dissolved
      concentration of 1.8 x 10(-6) mol L(-1) was furnished to bacteria, which was
      further used as food to the protozoan. The results showed that after bacterial
      growth, DOM concentration decreased as quantified by total organic carbon
      determinations. At the same time, free Cu2+ ions concentration increased in the
      medium. A lower copper concentration was detected in both microorganisms in the
      presence of DOM. We conclude that natural DOM reduced copper accumulation in the
      organisms on the first and second trophic levels, thus reducing the entrance of
      copper into the aquatic microbial food chain.

PMID- 19116732
TI  - Aesthetic plastic surgery: junior plastic surgeons' confidence in a training
      program.

PMID- 19116733
TI  - Fifty years of plastic surgery.

PMID- 19116736
TI  - Arachnomelia in Brown Swiss cattle maps to chromosome 5.
AB  - Arachnomelia in Brown Swiss cattle is a monogenic autosomal recessive inherited
      congenital disorder of the skeletal system giving affected calves a spidery look
      (OMIA ID 000059). Over a period of 20 years 15 cases were sampled in the Swiss
      and Italian Brown cattle population. Pedigree data revealed that all affected
      individuals trace back to a single acknowledged carrier founder sire. A genome
      scan using 240 microsatellites spanning the 29 bovine autosomes showed
      homozygosity at three adjacent microsatellite markers on bovine Chr 5 in all
      cases. Linkage analysis confirmed the localization of the arachnomelia mutation
      in the region of the marker ETH10. Fine-mapping and haplotype analysis using a
      total of 34 markers in this region refined the critical region of the
      arachnomelia locus to a 7.19-Mb interval on bovine Chr 5. The disease-associated
      IBD haplotype was shared by 36 proven carrier animals and allows marker-assisted
      selection. As the corresponding human and mouse chromosome segments do not
      contain any clear functional candidate genes for this disorder, the mutation
      causing arachnomelia in the Brown Swiss cattle might help to identify an unknown
      gene in bone development.

PMID- 19116734
TI  - Single port access laparoscopic cholecystectomy (with video).
AB  - BACKGROUND: Single port access (SPA) surgery is a rapidly evolving field due to
      the complexity of NOTES (natural orifice translumenal endoscopic surgery). SPA
      combines the cosmetic advantage of NOTES and possibility to perform surgical
      procedure with standard laparoscopic instruments. We report a technique of
      umbilical SPA cholecystectomy using standard laparoscopic instruments and
      complying with conventional surgical principle and technique of minimally
      invasive cholecystectomy. METHODS: Preliminary, prospective experience of SPA
      cholecystectomy in 11 patients (median age, 46 (range, 27-63) years) scheduled
      for cholecystectomy was evaluated. Diagnoses for cholecystectomy were:
      symptomatic gallbladder lithiasis (n = 7), previous acute cholecystitis (n = 3),
      and biliary pancreatitis (n = 1). RESULTS: SPA cholecystectomy was feasible in
      all patients (median body mass index, 24 (range, 20-34) kg/m(2)) who were
      scheduled for preliminary experience using conventional laparoscopic instruments.
      Median operative time was 52 (range, 40-77) minutes. Intraoperative
      cholangiography was performed in all patients, except one, and was considered
      normal. No peroperative or postoperative complications were recorded. Median
      hospital stay was less than 24 h. CONCLUSIONS: SPA cholecystectomy is feasible
      and seems to be safe when performed by experienced laparoscopic surgeons using
      standard laparoscopic instrumentation. SPA cholecystectomy may be safer than the
      NOTES approach at this time. It has to be determined whether this approach would
      benefit patients, other than cosmesis, compared with standard laparoscopic
      cholecystectomy.

PMID- 19116737
TI  - Impact of obesity on short-term results of laparoscopic rectal cancer resection.
AB  - INTRODUCTION: The influence of obesity [body mass index (BMI) >or= 30 kg/m(2)] on
      the outcome of laparoscopic colorectal surgery remains controversial. The
      complexity of rectal laparoscopic resections requires a specific assessment of
      the impact of obesity on the feasibility and short-term results of the surgery.
      METHODS: Between February 2002 and May 2007, 210 laparoscopic mesorectal
      excisions were performed. Demographic, oncologic and perioperative data were
      entered in a prospective database. Twenty-four patients (11.4%) with BMI over 30
      kg/m(2) formed the obese group (OG). The outcomes in the OG and the nonobese
      group (NOG) were compared. RESULTS: There were significantly more American
      Society of Anesthesiologists (ASA) score 3 patients (26% in OG versus 9% in NOG;
      p = 0.03) in the obese group. Obese patients experienced longer operative times
      (513 min in OG vs. 421 min in NOG; p < 0.01) and more frequent conversion to
      laparotomy (46% in OG vs. 12% in NOG; p < 0.001). Morbidity grade 1 was higher in
      the obese group (29.2% vs. 9.7% in NOG; p = 0.01), but there was no difference in
      regards to morbidity grade 2 or more (33.3% in OG vs. 32.3% in NOG). In addition,
      conversion to laparotomy among the obese did not increase significantly morbidity
      grade 2 or higher (5 of 11 for OG converted vs. 3 of 13 for OG nonconverted; p =
      0.39). Regarding the oncological parameters (e.g. number of lymph nodes removed,
      distal and lateral margins) there was no difference between groups. CONCLUSION:
      Obesity increases operative duration and conversion rate of rectal laparoscopic
      resection for cancer. Although obesity is associated with a worse preoperative
      evaluation, there is no increase in relevant morbidity and no impairment of
      oncological safety.

PMID- 19116738
TI  - Laparoscopic adrenalectomy for pheochromocytoma: take the vein last?
AB  - BACKGROUND: Traditionally, the adrenal vein has been ligated early during
      excision of a pheochromocytoma. Patient anatomy or size of the lesion can
      sometimes make early vein dissection difficult or unsafe. This study aimed to
      demonstrate the safety and efficacy of delayed adrenal vein ligation during
      laparoscopic adrenalectomy for pheochromocytoma. METHODS: A retrospective review
      of all laparoscopic adrenalectomies for pheochromocytoma from 1997 to 2007 was
      conducted. All the patients had confirmed histologic evidence of
      pheochromocytoma. The procedures were performed using the same technique, which
      involved division of the adrenal vein late in the procedure after the gland had
      been dissected free. Patient records were reviewed for evidence of intraoperative
      hemodynamic variations, blood loss, length of stay, and postoperative morbidity.
      RESULTS: The review examined 27 adrenalectomies performed for 25 patients.
      Intraoperative hypertension exceeding 170 mmHg was observed in seven patients
      (26.9%). The overall morbidity was 7.7%, and the mean length of hospital stay was
      1.7 days. No deaths occurred. CONCLUSIONS: Delayed adrenal vein ligation during
      laparoscopic adrenalectomy for pheochromocytoma is safe and effective. The
      intraoperative hemodynamic parameters are comparable with those reported in the
      literature for the "vein first" technique. Dividing the vein late is an
      alternative approach to laparoscopic excision of adrenal pheochromocytoma and
      should be considered in appropriate situations.

PMID- 19116739
TI  - Comparison of laparoscopic versus open liver tumor resection: a case-controlled
      study.
AB  - BACKGROUND: Although there are data in the literature about the safety and
      efficacy of laparoscopic liver resections, there are not many studies comparing
      laparoscopic versus open approaches in a case-matched design. The purpose of this
      study is to compare the perioperative outcome of laparoscopic versus open liver
      resections from a single institution. METHODS: Thirty-one patients underwent
      laparoscopic liver resection between April 1997 and August 2007, with a
      prospective laparoscopic program started in April 2006 (n=25). This group of
      patients was compared with 43 consecutive patients undergoing open resection who
      were matched by size of the lesion (5 cm or less for malignant and 8 cm or less
      for benign), anatomical location (segments 2, 3, 4b, 5, 6), and type of resection
      (wedge resection, segmentectomy, partial liver resection). Data were obtained
      from medical records as well as from a prospective database. Statistical analysis
      was performed using t-test and chi-square. All data are expressed as mean +/-
      standard error on the mean (SEM). RESULTS: Mean age in the laparoscopic group was
      57.6+/-2.7 years versus 61.9+/-2.3 years in the open group (p=0.2). There were
      more women in the laparoscopic group [74% females (n=23) and 26% males (n=8)]
      versus in the open group [40% females (n=17) and 60% males (n=26)] (p=0.003).
      There were more patients with malignant lesions in the open group (73%) versus in
      the laparoscopic group (45%) (p=0.01). Eight patients underwent partial and 23
      patients segmental/wedge liver resection in the laparoscopic group versus 15
      patients who underwent partial and 28 patients segmental/wedge liver resection in
      the open group (p=0.7). Mean tumor size was 3.9+/-0.4 cm in the laparoscopic
      group versus 4.2+/-0.3 cm in the open group (p=0.5). Ten (32%) out of 31 cases in
      the laparoscopic group were hand-assisted. Inflow occlusion was used in 1 case
      (3%) in the laparoscopic group versus 16 (37.2%) in the open group. Mean
      operating time was 201+/-15 min for the laparoscopic group and 172+/-12 min for
      the open group (p=0.1). Mean estimated blood loss during the procedure was
      122.5+/-45.4 cc for the laparoscopic group and 299.6+/-33.6 cc for the open group
      (p=0.002). Surgical margin was similar for malignant cases in both groups. Mean
      hospital stay was 3.2+/-1.0 days for the laparoscopic group and 6.8+/-0.7 days
      for the open group (p=0.004). The incidence of postoperative complications was
      13% (n=4) in the laparoscopic and 16% (n=7) in the open group (p=0.7).
      CONCLUSION: This study shows that, with a longer operative time, the laparoscopic
      approach, despite the learning curve, offers advantages regarding operative blood
      loss, postoperative analgesic requirement, time to regular diet, hospital stay,
      and overall cost compared with the open approach for minor liver resections.

PMID- 19116740
TI  - Laparoscopic-assisted anterior resection with double-stapling technique
      anastomosis: safe and feasible for lower rectal cancer?
AB  - BACKGROUND: Laparoscopic surgery for rectal cancer has been considered more
      demanding than laparoscopic colectomy due to its technical difficulties.
      OBJECTIVE: The aim of this study was to show safety and feasibility of
      laparoscopic low anterior resection for lower rectal cancer reconstructed by
      double-stapling technique (DST). METHODS: The present study reviewed 159 patients
      with rectal cancer undergoing laparoscopic anterior resection reconstructed by
      DST. They were subdivided into two groups: 98 patients with upper rectal cancer
      located between 75 and 150 mm from the anal verge (group A) and 61 with lower
      rectal cancer located within 75 mm from the anal verge (group B). Short-term
      results and pathological findings were compared between the two groups. RESULTS:
      There was no conversion in both groups. Operating time and intraoperative blood
      loss were similar in the two groups. No mortality occurred in either group.
      Overall morbidity rate was 10.2% in group A and 11.5% in group B (p = 0.798).
      Anastomotic leak rate was similar in the two groups (2.0% in group A versus 3.3%
      in group B; p = 0.638). Pathological examination of resected specimen showed no
      involvement of distal resection margin or circumferential resection margin in
      both groups. CONCLUSIONS: The present study shows that laparoscopic surgery is
      safe and feasible for lower rectal cancer in a very select group of patients.

PMID- 19116741
TI  - Multidimensional analysis of the learning curve for laparoscopic colorectal
      surgery: lessons from 1,000 cases of laparoscopic colorectal surgery.
AB  - PURPOSE: We consider quality of surgery throughout the learning curve and attempt
      to determine the learning curve for competency in performing laparoscopic
      colorectal surgery. METHODS: The study included 1,014 patients who underwent
      laparoscopic colorectal resection between June 1996 and December 2007. We
      categorized patients into nine periods according to number of cases performed.
      RESULTS: Operative time continuously decreased for right hemicolectomy (216
      versus 150 min) and anterior resection (214.8 versus 147.7 min), whereas for low
      anterior resection it did not change over many periods and then significantly
      decreased after the ninth period (221.3 versus 176.4 min). The proportion of
      patients who had undergone previous abdominal surgery increased after the second
      period. Anastomotic leakage rate was 6-9% for the first 200 cases, and then
      decreased to less than 2%. More than 10% of operations were converted to open
      surgery during the first period, after which this rate significantly decreased to
      2%. Number of harvested lymph nodes stabilized to 35-40 for right hemicolectomy
      after 200 cases, whereas for anterior and low anterior resection it was
      consistently 15-20 after the initial 20 cases. Overall, disease recurrence rate
      was 16-25%. For rectal cancer, local recurrence rate was highest (12%) in the
      fourth period and decreased thereafter to about 3%. CONCLUSION: Postoperative
      complications and local recurrence rate increased even after accumulation of
      experience because of expansion of indications for laparoscopic procedures.

PMID- 19116742
TI  - Safe and feasible inflow occlusion in laparoscopic liver resection.
AB  - BACKGROUND: A major challenge in laparoscopic liver resection to avoid massive
      hemorrhage from the transection plane. METHODS: This study investigated 32
      consecutive patients who underwent laparoscopic or laparoscopically assisted
      hepatic resection and had the hepatoduodenal ligament encircled by vessel tape
      using an Endo Retract Maxi as a tourniquet for complete interruption of blood
      inflow to the liver. RESULTS: Laparoscopic encircling of the hepatoduodenal
      ligament was performed in a few minutes without any complications for any of the
      32 patients. CONCLUSIONS: Laparoscopic Pringle's maneuver using an Endo Retract
      Maxi can be performed easily for all patients undergoing laparoscopic liver
      resection.

PMID- 19116743
TI  - For patients with predicted low risk for choledocholithiasis undergoing
      laparoscopic cholecystectomy, selective intraoperative cholangiography and
      postoperative endoscopic retrograde cholangiopancreatography is an effective
      strategy to limit unnecessary procedures.
AB  - BACKGROUND: There is debate about whether intraoperative cholangiography (IOC)
      should be performed routinely or selectively during laparoscopic cholecystectomy
      (LC) in patients with suspected choledocholithiasis. The timing of endoscopic
      retrograde cholangiopancreatography (ERCP) in these patients also is an issue. We
      reviewed the experience in our center, where a management algorithm limiting ERCP
      in relation to LC was adopted. METHODS: We retrospectively reviewed every LC
      performed by one surgeon during 6 years and the related ERCPs. RESULTS: A total
      of 264 LCs were performed. In 30 patients, stones were cleared or excluded by
      preoperative ERCP. In the remaining 234 LCs, 31 of 34 IOCs were successfully
      performed. Two of 31 IOCs were positive for bile duct stones; stone removal was
      successful in each patient at subsequent ERCP. Only 10 of 201 patients who did
      not have IOC required postsurgical ERCP within 10 weeks of LC, 3 of whom had
      common bile duct stones at ERCP. CONCLUSIONS: For patients who underwent LC, we
      performed selective IOC with postoperative ERCP for positive studies. Review of
      our experience using this algorithm showed it to be a powerful tool in limiting
      unnecessary ERCPs. Our data suggest that routine preoperative ERCP cannot be
      justified. Selective IOC during LC misses relatively few cases of biliary stones;
      these can be managed quickly by experienced endoscopists.

PMID- 19116744
TI  - Perioperative outcomes of laparoscopic transhiatal inversion esophagectomy
      compare favorably with those of combined thoracoscopic-laparoscopic
      esophagectomy.
AB  - AIMS: Wide acceptance of laparoscopic esophagectomy has been hampered by the
      technical difficulty of the procedure and inconsistent improvements in morbidity
      and mortality. Most case series have utilized a combined thoracoscopic
      laparoscopic approach (TLE), but laparoscopic inversion esophagectomy (LIE), a
      method of transhiatal esophagectomy, has been proposed as an alternative.
      Inversion esophagectomy simplifies retraction and improves exposure during the
      mediastinal dissection; however, no previous studies have directly compared LIE
      outcomes with those of the combined approach. METHODS: Between July 2003 and
      March 2008, 70 consecutive patients underwent minimally invasive esophagectomy by
      LIE (N = 40) or TLE (N = 30). Data for all patients were collected prospectively
      and stored in a relational database. Recorded outcome measures included operative
      time, blood loss, length of hospital stay, intensive care unit stay, and
      perioperative complications. RESULTS: There were no significant differences in
      patient age, gender, body mass index (BMI), or American Society of
      Anesthesiologists (ASA) class between the groups, but LIE patients had lower
      stage of esophageal cancer, and were less likely to have received induction
      chemoradiotherapy than TLE patients. Patients undergoing LIE had significantly
      lower operative time (398 vs. 537 min, p < 0.001), intraoperative blood loss (100
      vs. 200 ml, p < 0.001), and overall length of stay (9 vs. 14 days, p = 0.003)
      compared with TLE patients. LIE yielded a median of 10 lymph nodes removed
      compared with 13 for TLE (p = 0.016). Atrial arrhythmia and postoperative
      pneumonia were less common in LIE patients than in TLE patients, occurring in
      17.5% vs. 27.1% (p = 0.036), and in 7.5% vs. 15.7% of cases (p = 0.029),
      respectively. CONCLUSION: LIE provides safe and effective approach to minimally
      invasive esophagectomy for patients with early esophageal cancer and high-grade
      dysplasia. Compared with TLE, inversion esophagectomy requires less operative
      time and has lower operative blood loss and length of hospital stay. LIE may also
      result in fewer perioperative cardiac and pulmonary complications compared with
      TLE. Based on these results, we reserve TLE for more advanced esophageal cancer
      and those undergoing preoperative radiochemotherapy.

PMID- 19116745
TI  - Development of an articulating ultrasonically activated device for laparoscopic
      surgery.
AB  - BACKGROUND: Ultrasonically activated devices (USADs) offer excellent coagulating
      dissection performance and are broadly used, particularly in endoscopic
      operations. Traditional USADs, however, have fixed linear shape and are thus
      limited in the directions from which organs can be approached. We have developed
      a small USAD transducer attached to the tip of an articulating device, offering a
      new kind of USAD in which the tip can bend as desired. We describe herein an
      evaluation of the coagulating dissection performance of this new articulating
      USAD and an in vivo confirmation of clinical usefulness. METHODS: To evaluate
      coagulating dissection performance, we compared coagulating shearing on porcine
      splenic arteries between the articulating USAD and a Harmonic Scalpel II (HSII),
      representing a traditional USAD. Changing the amplitude of vibration between 60
      microm and 80 microm and grip force among 1, 2, and 3 N, we measured the time
      required for division and bursting pressure of coagulating dissection. An in vivo
      experiment in a pig was also used to confirm the usefulness of the articulating
      USAD in laparoscopic operations. RESULTS: Division time did not differ
      significantly between the articulating USAD and HSII with an 80-microm amplitude
      of vibration and a grip force of 2 or 3 N. Bursting pressure of blood vessels
      showed no significant difference between articulating USAD and HSII under all
      experimental conditions. In the in vivo experiment, the new bendable tip of the
      articulating USAD displayed coagulating dissection performance equivalent to that
      of the traditional USAD. CONCLUSIONS: We have developed a new articulating USAD
      that can broaden the range of methods and approaches available for USADs and
      improve usefulness and safety.

PMID- 19116746
TI  - Predictive factors for surgical complications of laparoscopy-assisted distal
      gastrectomy for gastric cancer.
AB  - BACKGROUND: Some studies have found high incidences of intraoperative and
      postoperative complications for patients with gastric cancer. To determine the
      predictive factors for the surgical complications of laparoscopic gastric
      surgery, surgical outcomes were evaluated. METHODS: Between April 2002 and
      December 2007, 152 patients with preoperatively diagnosed early gastric cancer
      who underwent laparoscopy-assisted distal gastrectomy (LADG) were enrolled.
      Visceral (VFA) and subcutaneous fat areas (SFA) were assessed by Fat Scan
      software. The predictive factors for surgical complications of LADG were
      evaluated by univariate and logistic regression analyses. RESULTS: Of 152
      patients, conversion to open surgery due to uncontrollable bleeding was observed
      in nine male patients, and postoperative complications were detected in seven
      male and one female patient (four anastomotic leakage, two intraabdominal
      abscess, one pancreatic fistula, and one lymphorrhea). High body mass index (BMI)
      and high VFA independently predicted conversion to open surgery and postoperative
      complications. VFA was significantly higher, operation time was longer, blood
      loss was greater, and SFA was lower in male than in female patients, whereas no
      significant difference was observed in BMI between male and female patients.
      CONCLUSIONS: High BMI and high VFA can predict technical difficulties during
      laparoscopic gastric surgery and postoperative complications. Particularly, LADG
      should be performed cautiously to prevent surgical complications for male
      patients with high VFA. Predictive impact of VFA should be further determined in
      a larger set of patients.

PMID- 19116747
TI  - Intraoperative monitoring of laparoscopic skill development based on quantitative
      measures.
AB  - BACKGROUND: Methods for evaluating standard skills in the operating room
      typically are based on direct observation and checklists, but such evaluations
      are time consuming and can be subject to bias. It often is possible to acquire
      more objective measurements using surgical simulators. However, motor performance
      in simulators can differ significantly from that in the operating room.
      Intraoperative assessment is particularly challenging because of the significant
      variability between procedures related to differences in the patients, the
      surgical setup, and the team. This study aimed to evaluate the feasibility of
      using a new framework for interpreting quantitative measures acquired in the
      operating room to distinguish between levels of laparoscopic skill development.
      METHODS: Two levels of surgical skill development were observed, namely, those of
      three fourth-year residents and three attending surgeons performing three
      laparoscopic cholecystectomies each. Electromagnetic position sensors were
      attached by the surgeons to a 5-mm curved dissector and a 5-mm atraumatic
      grasper. From the tools' position histories and video recordings, time,
      kinematics, and movement transition measures were extracted. Various measures
      such as the Kolmogorov-Smirnov statistic and the Jensen-Shanon Divergence were
      used to provide intuitive dimensionless difference measures ranging from 0 to 1.
      These scores were used to compare residents and expert surgeons executing two
      surgical tasks: exposure of Calot's triangle and dissection of the cystic duct
      and artery. RESULTS: The two groups could be clearly differentiated in both tasks
      during monitoring for the dominant hand (analysis of variance [ANOVA] and Mann
      Whitney; p < 0.05) but not for the nondominant hand. CONCLUSIONS: It is practical
      to acquire time, kinematic, and movement transition measures intraoperatively
      using video and electromagnetic position-sensing technologies. Principal
      component analysis proved to be a useful technique for presenting differences
      between skill levels based on those measures. The authors conclude that objective
      assessment of intraoperative surgical motor behavior is feasible and likely
      practical.

PMID- 19116748
TI  - A novel endoesophageal magnetic device to prevent gastroesophageal reflux.
AB  - BACKGROUND: Endoscopic methods to prevent gastroesophageal reflux (GER) show
      scarce effectiveness and may narrow the esophageal lumen more or less stiffly,
      sometimes impairing bolus transit and leading to dysphagia. The aim of this study
      was to demonstrate the possibility of reinforcing lower esophageal sphincter
      (LES) tone by implanting endoluminally a magnetic device. MATERIALS AND METHODS:
      The device consists of two small magnetic plaques to be implanted in the
      submucosa close to LES with opposite polarities facing so that they attract one
      other, closing the esophageal lumen. The magnets were implanted by means of a
      special endoluminal device in five esophageal-gastric ex vivo specimens taken
      from swine. Variation in endoluminal pressure at the LES level was measured by
      means of slow pull-through of a thin side-hole manometric catheter in each
      specimen, before and after insertion of the magnets. RESULTS: The new high
      pressure zone exhibited a length of about 2 cm and a pressure of 14.2+/-1.27 mmHg
      [mean +/- standard deviation (SD)], significantly (p<0.001) higher than that
      measured before insertion of the magnetic valve (1.5+/-0.26 mmHg). CONCLUSIONS:
      The present research demonstrates that it is possible to create at the LES level
      a dynamic closure of a value considered sufficient to prevent GER, by implanting
      in the esophageal submucosa of anatomical specimens a magnetic device by means of
      a special endoluminal probe. Once effectiveness and tolerability of magnets
      covered by a biocompatible sheath have been demonstrated in vivo, this device
      could become a simple and effective nonsurgical solution to GER.

PMID- 19116749
TI  - Video-assisted thoracic surgery (VATS) for resection of metastatic adenocarcinoma
      as an acceptable alternative.
AB  - BACKGROUND: Adenocarcinomas commonly metastasize to the lungs and can be resected
      using open thoracotomy or video-assisted thoracic surgery (VATS). This study
      reviews metastatic resections in primary adenocarcinoma patients, using both
      thoracotomy and VATS. We aim to compare long-term prognoses to test the efficacy
      and viability of VATS. METHODS: A retrospective review of primary adenocarcinoma
      patients who underwent resection of pulmonary metastases from 1990 to 2006 was
      carried out. Information was obtained by chart review. Endpoints analyzed were
      disease-free interval (DFI), survival time, and recurrence-free survival (RFS).
      RESULTS: In a total of 42 (16 male, 26 female; median age 58.5 years) primary
      adenocarcinoma patients, 21 patients underwent first pulmonary metastatic
      resection using VATS (7 male, 14 female; median age 57 years) and 21 using
      thoracotomy (9 male, 12 female; median age 59 years). Primary adenocarcinomas
      were mainly 27 colorectal (64%) and 11 breast (26%). Two VATS (10%) and three
      open patients (14%) had local recurrences of the original cancer. Median
      postoperative follow was 13.3 months [interquartile range (IQR) 4.5-32.8 months]
      for VATS and 36.9 months (IQR 19.3-48.6 months) after thoracotomy. Median DFI-1
      was 22.3 months (IQR 13.5-40.6 months) for VATS patients and 35.6 months (IQR
      26.7-61.3 months) for open patients. Second thoracic occurrences were noted in
      six VATS patients (median DFI-2 9.2 months), and in seven open patients (median
      DFI-2 21.5 months). Third thoracic occurrences were noted in one VATS patient
      (DFI-3 18.7 months) and in one thoracotomy patient (DFI-3 21.8 months). Odds
      ratio of recurrence showed 12.5% less chance of developing recurrence in VATS
      patients. Five-year RFS was 53% in VATS and 57% in thoracotomy patients.
      CONCLUSIONS: VATS has become a viable alternative to open thoracotomy for
      resection of pulmonary metastases. In cases of primary adenocarcinoma, VATS
      showed no increase in number of thoracic recurrences, and comparable RFS. Short
      term follow-up is encouraging; long-term follow-up will be needed to confirm
      these results.

PMID- 19116751
TI  - Lymph node evaluation and long-term survival in Stage II and Stage III colon
      cancer: a national study.
AB  - BACKGROUND: The most important prognostic factor in colonic cancer is the
      presence or absence of regional lymph nodes metastases. The aim of this study was
      to evaluate the relationship between 5-year mortality in the New Zealand
      population, and the number of nodes examined in Stage II and III colon cancers.
      METHODS: New Zealand Cancer Registry data were retrieved for patients with
      colonic cancer from January 1995 to July 2003. Patients with incomplete entries,
      Stage I tumors, and distant metastases were excluded from analysis. Univariate
      and Cox regression models were used with 5-year mortality as the primary
      endpoint. RESULTS: The study identified 4309 patients. Younger age, female
      gender, Pacific Island descent, and right-sided tumors were associated with
      significantly higher lymph node retrieval. Cox regression analysis showed that
      the number of nodes examined was a significant predictor of 5-year mortality when
      age, sex, ethnicity, and site were controlled for. Five-year survival
      consistently improved between nodal strata until the 16-node mark, above which
      survival advantage was minimal. For Stage III cancers, a higher lymph node ratio
      was associated with a significant increase in mortality. CONCLUSIONS: Increased
      rates of nodal examination are associated with a significantly lower 5-year
      mortality for Stage II and III colonic cancer, but this survival advantage
      appears to be minimal after the 16-node mark. The lymph node ratio has been
      validated as a powerful predictor of survival in Stage III cancer. Our results
      support the current practice of harvesting and examining as many nodes as
      possible during attempted curative resection.

PMID- 19116750
TI  - Open randomized clinical trial of laparoscopic versus open incisional hernia
      repair.
AB  - BACKGROUND: Incisional hernia is a common complication following abdominal
      surgery. Although the use of prosthetics has decreased recurrence rates, the
      standard open approach is still unsatisfactory. Laparoscopic techniques are an
      attempt to provide similar outcomes with the advantages of minimally invasive
      surgery. METHODS: Open randomized controlled clinical trial with follow-up at 1,
      2, 3, 7, and 15 days, and 1, 3, and 12 months from hernia repair. The study was
      carried out in the surgery departments of three general hospitals of the Valencia
      Health Agency. OBJECTIVES: To compare laparoscopic with anterior open repair
      using health-related quality of life outcomes as main endpoints. RESULTS: Eighty
      four patients with incisional hernia were randomly allocated to an open group
      (OG) (n = 39) or to a laparoscopic group (LG) (n = 45). Seventy-four patients
      completed 1-year follow up. Mean length of stay and time to oral intake were
      similar between groups. Operative time was 32 min longer in the LG (p < 0.001).
      Conversion rate was 11%. The local complication rate was superior in the LG
      (33.3% versus 5.2%) (p < 0.001). Recurrence rate at 1 year (7.9% versus 9.7%) was
      similar in the two groups. There were no significant differences in the pain
      scores or the EQ5D tariffs between the two groups during follow-up. CONCLUSIONS:
      Laparoscopic incisional hernia repair does not seem to be a better procedure than
      the open anterior technique in terms of operative time, hospitalization,
      complications, pain or quality of life.

PMID- 19116753
TI  - Bedside talc pleurodesis for malignant pleural effusion: factors affecting
      success.
AB  - INTRODUCTION: To determine the factors affecting the success of bedside talc
      slurry (TS) used for symptomatic treatment of patients with malignant pleural
      effusion (MPE). METHODS: Data of 113 effusions in 103 MPE patients treated
      between 1999 and 2007 were retrospectively evaluated for the study. The study
      group involved 73 patients whose follow-up information was available out of 81
      patients treated by TS. Causes of MPE were lung cancer in 22 patients (30.1%) and
      breast carcinoma in 21 patients (28.8%). RESULTS: The success rate of TS was
      significantly higher if the time period between radiological diagnosis of
      effusion and administration of TS was less than 30 days (P= .02), or spontaneous
      expansion was attained after chest tube drainage (CTD) (P= .01). Success rate was
      higher for patients with daily drainage of less than 200 ml before TS than
      patients with more than 200 ml of daily drainage (P= .01). Dose of talc, either 4
      g or above (P= .34), primary cause of MPE (P= .53), time to termination of CTD
      (P= .57), amount of drainage when CTD was terminated (P= .23), and time period
      between CTD and administration of TS (P= .20) did not show a statistically
      significant effect on the success of TS. CONCLUSION: In the treatment of
      malignant pleural effusion, patients with daily drainage of less than 200 ml
      before TS developed less recurrence than patients with daily drainage of more
      than 200 ml. Longer time period between the diagnosis of MPE and onset of CTD
      increased recurrence.

PMID- 19116754
TI  - Circulating cancer cells: could they be used in the clinic as recurrence markers
      for gastric and colorectal cancer?

PMID- 19116755
TI  - Inhibition of autophagy by 3-MA enhances the effect of 5-FU-induced apoptosis in
      colon cancer cells.
AB  - BACKGROUND: 5-fluorouracil-(5-FU)-based adjuvant chemotherapy is widely used for
      the treatment of colorectal cancer. However, 5-FU resistance in the course of
      treatment has become more common. Therefore, new therapeutic strategies and/or
      new adjuvant drugs still need to be explored. METHODS: Two colon-cancer-derived
      cell lines, colon26 and HT29, were used to investigate the effect of 5-FU, 3
      methyladenine (3-MA, an autophagy inhibitor), or their combination on apoptotic
      cell death and autophagy. MTT assay, Hochest plus propidium iodide (PI) staining,
      and DNA fragmentation assay were used to observe apoptosis. Meanwhile,
      monodansylcadaverine (MDC) was used to detect autophagy. Finally, immunoblotting
      assay was used to explore the molecular change that occurred. RESULTS: We
      observed the apoptosis induced by 5-FU in colon cancer cells. Meanwhile,
      autophagy was also stimulated. The combination treatment of 3-MA and 5-FU
      significantly increased the apoptotic cell death. By isolating the subcellular
      fractions of mitochondria and cytosol, we observed that the release of cytochrome
      c was increased in combination-treated cells. Cytochrome c resulted in the
      activation of caspase-3, thus activating PARP. Moreover, the anti-apoptotic
      protein, Bcl-xL, was significantly downregulated by 3-MA. CONCLUSIONS: Our
      results suggest that 5-FU-induced apoptosis in colon cancer cells can be enhanced
      by the inhibitor of autophagy, 3-MA. Autophagy might play a role as a self
      defense mechanism in 5-FU-treated colon cancer cells, and its inhibition could be
      a promising strategy for the adjuvant chemotherapy of colon cancer.

PMID- 19116756
TI  - Tumor-associated macrophage correlated with angiogenesis and progression of
      mucoepidermoid carcinoma of salivary glands.
AB  - BACKGROUND: There is considerable controversy about whether tumor-associated
      macrophages (TAMs) promote or inhibit tumor progression. The present study
      examined the clinicopathologic significance of TAMs and their association with
      tumor angiogenesis, cell proliferation, and apoptosis in mucoepidermoid carcinoma
      (MEC). The potential effect of TAMs on cancer cells was also investigated.
      METHODS: CD68, CD34, Ki-67, and vascular endothelial growth factor (VEGF)-A
      immunohistochemical staining and terminal deoxynucleotidyl transferase-mediated
      dUTP nick-end labeling (TUNEL) were applied to samples from 41 MEC patients. The
      biologic effect of macrophages on MEC cancer cells was examined in a co-culture
      system. RESULTS: The proliferation index (PI) was 11.7+/-5.9%, and the apoptotic
      index (AI) was 4.1+/-2.3% in cancer patients. PI was significantly correlated
      with tumor grade, and the PI/AI ratio was significantly correlated with tumor
      size and stage. The distributions of intratumoral TAMs and microvessel density
      (MVD) were heterogeneous. TAM count associated strongly with tumor size, grading,
      and MEC staging. A greater intratumoral MVD was observed frequently in patients
      with large, intermediate/high-grade, and advanced-stage tumors. VEGF-A expression
      correlated significantly with tumor size and stage. MVD count was closely
      associated with TAM count and VEGF-A expression. Co-cultured cancer cells with
      macrophages increased migration and invasion ability of cancer cells. Co-cultured
      endothelial cells with cancer cells elevated VEGF-A expression, proliferation,
      and migration, and tube formation of endothelial cells. CONCLUSION: Our data
      suggest that TAMs play a tumor-promoting role in MEC. The TAM count, intratumoral
      MVD, and PI/AI ratio are potentially useful markers of progression in patients
      with MEC.

PMID- 19116757
TI  - Readmission after pancreaticoduodenectomy: an issue of survival and survivorship.

PMID- 19116758
TI  - Development of a zebrafish spleen cell line, ZSSJ, and its growth arrest by gamma
      irradiation and capacity to act as feeder cells.
AB  - A zebrafish spleen cell line, ZSSJ, was developed and its growth arrest by gamma
      radiation determined and its capacity to stimulate the proliferation of the
      zebrafish blastula cell line, ZEB2J, measured. ZSSJ was initiated by explant
      outgrowth, grew adherent with mainly an epithelial-like morphology, and stained
      strongly for alkaline phosphatase. ZSSJ was not only grown in L-15 with 15% fetal
      bovine serum at 26 degrees C to 28 degrees degrees C but also grew at room
      temperature. Cultures of ZSSJ have undergone approximately 40 population
      doublings, had few cells staining for b-galactosidase activity, which is commonly
      present in senescent cultures, and many cells with an aneuploid karyotype, which
      is frequently associated with immortalization. ZSSJ growth was arrested by 30 to
      50 Gy of g-irradiation, whereas after 20 Gy, some slight growth was observed. By
      contrast, growth of the rainbow trout spleen stromal cell line, RTS34st, which
      has been used as a feeder for zebrafish ES cell cultures, was arrested completely
      by 20 Gy. In cocultures, nongrowth-arrested ZSSJ stimulated ZEB2J proliferation
      better than growth-arrested ZSSJ and better than RTS34st. ZSSJ should be useful
      as a feeder cell line for zebrafish ES cell cultures.

PMID- 19116760
TI  - FLEXIBLE CULM 1 encoding a cinnamyl-alcohol dehydrogenase controls culm
      mechanical strength in rice.
AB  - Culm mechanical strength is an important agronomic trait in crop breeding. To
      understand the molecular mechanisms that control culm mechanical strength, we
      identified a flexible culm1 (fc1) mutant by screening a rice T-DNA insertion
      mutant library. This mutant exhibited an abnormal development phenotype,
      including late heading time, semi-dwarf habit, and flexible culm. In this study,
      we cloned the FLEXIBLE CULM1 (FC1) gene in rice using a T-DNA tagging approach.
      FC1 encodes a cinnamyl-alcohol dehydrogenase and is mainly expressed in the
      sclerenchyma cells of the secondary cell wall and vascular bundle region. In
      these types of cells, a deficiency of FC1 in the fc1 mutant caused a reduction in
      cell wall thickness, as well as a decrease in lignin. Extracts from the first
      internodes and panicles of the fc1 plants exhibited drastically reduced cinnamyl
      alcohol dehydrogenase activity. Further histological and biochemical analyses
      revealed that the p-hydroxyphenyl and guaiacyl monomers in fc1 cell wall were
      reduced greatly. Our results indicated that FC1 plays an important role in the
      biosynthesis of lignin and the control of culm strength in rice.

PMID- 19116761
TI  - Sorption and bioavailability of arsenic in selected Bangladesh soils.
AB  - The bioavailability of arsenic (As) in the soil environment is largely governed
      by its adsorption-desorption reactions with soil constituents. We have
      investigated the sorption-desorption behaviour of As in four typical Bangladeshi
      soils subjected to irrigation with As-contaminated groundwater. The total As
      content of soils (160 samples) from the Laksham district ranged from <0.03 to
      approximately 43 mg kg(-1). Despite the low total soil As content, the
      concentration of As in the pore water of soils freshly irrigated with As
      contaminated groundwater ranged from 0.01 to 0.1 mg l(-1). However, when these
      soils were allowed to dry, the concentration of As released in the pore water
      decreased to undetectable levels. Remoistening of soils to field moisture over a
      10-day period resulted in a significant (up to 0.06 mg l(-1)) release of As in
      the pore water of soils containing >10 mg As kg(-1) soil, indicating the
      potential availability of As. In soils containing <5 mg As kg(-1), As was not
      detected in the pore water. A comparison of Bangladeshi soils with strongly
      weathered long-term As-contaminated soils from Queensland, Australia showed a
      much greater release of As in water extracts from the Australian soils. However,
      this was attributed to the much higher loading of As in these Australian soils.
      The correlation of pore water As with other inorganic ions (P, S) showed a
      strongly significant (P < 0.001) relationship with P, although there was no
      significant relationship between As and other inorganic cations, such as Fe and
      Mn. Batch sorption studies showed an appreciable capacity for both As(V) and
      As(III) sorption, with As(V) being retained in much greater concentrations than
      As(III).

PMID- 19116763
TI  - Gestalt-binding of tropomyosin to actin filaments.
AB  - We argue that the overall behavior of tropomyosin on F-actin cannot be easily
      discerned by examining thin filaments reduced to their smallest interacting
      units. In isolation, the individual interactions of actin and tropomyosin, by
      themselves, are too weak to account for the specificity of the system. Instead
      the association of tropomyosin on actin can only be fully explained after
      considering the concerted action of the entire acto-tropomyosin system. We
      propose that the low K ( a ) describing tropomyosin:actin interaction, when taken
      together with the form-fitting complementarity of tropomyosin strands on F-actin
      and the tendency for tropomyosin to polymerize end-to-end, make possible unique
      thin filament functions both locally and at higher levels of filament
      organization.

PMID- 19116762
TI  - The role of the MTA family and their encoded proteins in human cancers: molecular
      functions and clinical implications.
AB  - MTA (metastasis-associated gene) is a newly discovered family of cancer
      progression-related genes and their encoded products. MTA1, the first gene found
      in this family, has been repeatedly reported to be overexpressed along with its
      protein product MTA1 in a wide range of human cancers. In addition, the
      expression of MTA1/MTA1 correlates with the clinicopathological properties
      (malignant properties) of human cancers. MTA proteins are transcriptional co
      repressors that function in histone deacetylation and are involved in the NuRD
      complex, which contains nucleosome remodeling and histone deacetylating
      molecules. MTA1 expression correlates with tumor formation in the mammary gland.
      In addition, MTA1 converts breast cancer cells to a more aggressive phenotype by
      repression of the estrogen receptor (ER) alpha trans-activation function through
      deacetylation of the chromatin in the ER-responsive element of ER-responsive
      genes. Furthermore, MTA1 plays an essential role in c-MYC-mediated cell
      transformation. Another member of this family, MTA3, is induced by estrogen and
      represses the expression of the transcriptional repressor Snail, a master
      regulator of "epithelial to mesenchymal transitions", resulting in the expression
      of the cell adhesion molecule E-cadherin and maintenance of a differentiated,
      normal epithelial phenotype in breast cells. In addition, tumor suppressor p53
      protein is deacetylated and inactivated by both MTA1 and MTA2, leading to
      inhibition of growth arrest and apoptosis. Moreover, a hypoxia-inducible factor
      1alpha (HIF-1alpha) is also deacetylated and stabilized by MTA1, resulting in
      angiogenesis. Thus, MTA proteins, especially MTA1, represent a possible set of
      master co-regulatory molecules involved in the carcinogenesis and progression of
      various malignant tumors. MTA proteins are proposed to be important new tools for
      clinical application in cancer diagnosis and treatment.

PMID- 19116764
TI  - Validation of forehead venous pressure as a measure of respiratory effort for the
      diagnosis of sleep apnea.
AB  - OBJECTIVES: The aim of the study was to validate the measurement of Forehead
      Venous Pressure derived from a single site on the forehead as an alternative to
      esophageal manometry and respiratory effort bands in the differential diagnosis
      of sleep apnea. METHODS: Fourteen subjects underwent a laboratory polysomnography
      concurrently with ARES Unicorder at Walter Reed Army Medical Center. Two-hundred
      respiratory events were selected by a scorer boarded in sleep medicine and
      classified into six event categories used in the differential diagnosis of sleep
      disordered breathing. Four sets of events were prepared, each containing airflow
      and one of four measures of respiratory effort (i.e., esophageal manometer, chest
      and abdomen bands, and forehead venous pressure). A second board-certified scorer
      scored each set of events twice while blinded to the type of the effort signal.
      RESULTS: The inter-rater Kappa scores across all event types indicated all four
      effort signals provided moderate agreement (kappa = 0.43-0.47). When comparing
      the intra-rater Kappa scores, the chest belt was superior (kappa = 0.88) to the
      esophageal manometry, FVP and abdomen belt (kappa = 0.78-0.82). The Kappa scores
      for the intra-rater comparison with the esophageal serving as the gold standard,
      FVP abdomen and chest all showed near perfect agreement (kappa = 0.81-0.86). The
      esophageal manometer and FVP provided slightly better inter-rater agreement in
      the detection of both obstructive hypopneas and apneas as compared to the chest
      and abdomen belts. There was a 20-30% drop in inter-rater reliability in the
      detection of flow-limitation and ventilation-change events compared to
      obstructive events, and all effort signals showed poor inter-rater agreement for
      central and mixed events. CONCLUSIONS: The results of the study suggest that the
      FVP can serve as an alternative to respiratory bands in the differential
      diagnosis of sleep disordered breathing, and in the recognition of patients
      appropriate for bilevel continuous positive airway pressure devices.

PMID- 19116765
TI  - Prospective study of physical activity and the risk of ovarian cancer.
AB  - BACKGROUND: Available studies on physical activity and ovarian cancer have
      produced inconsistent findings, with some previous studies reporting a positive
      association between vigorous physical activity and ovarian cancer risk. METHODS:
      We prospectively investigated the relations of self-reported moderate and
      vigorous physical activity to ovarian cancer in a cohort of 96,216 US women aged
      51-72 years at baseline, followed from 1996-1997 to 31 December 2003. RESULTS:
      During seven years of follow-up, we documented 309 cases of epithelial ovarian
      carcinoma. In analyses adjusted for age, the relative risks (RRs) of ovarian
      cancer for individual and joint combinations of moderate and vigorous physical
      activity such as entirely inactive, neither moderate nor vigorous physical
      activity, moderate physical activity only, vigorous physical activity only, and
      both moderate and vigorous physical activity were 0.88, 1.0 (reference), 0.89,
      1.05, and 1.08 (95% confidence interval (CI) = 0.81-1.43, respectively. After
      multivariate adjustment, the relation was essentially unchanged (RR comparing
      women with both moderate and vigorous physical activity to those with neither
      moderate nor vigorous physical activity = 1.10; 95% CI = 0.82-1.48). The null
      association between physical activity and ovarian cancer persisted in subgroups
      of women as defined by body mass index, parity, oral contraceptive use,
      menopausal hormone therapy, family history of ovarian cancer, and other variables
      (all p values for interaction >0.05). CONCLUSIONS: Neither moderate nor vigorous
      physical activity showed a statistically significant association with ovarian
      cancer in this large cohort of women.

PMID- 19116766
TI  - Tyrosine phosphatase beta regulates angiopoietin-Tie2 signaling in human
      endothelial cells.
AB  - OBJECTIVES: The endothelial cell (EC)-selective receptor tyrosine kinase, Tie2,
      and its ligands angiopoietin Ang-1 and Ang-2, are essential for blood vessel
      maintenance and repair. Ang-1 is an agonist of Tie2 receptor activation, whereas
      Ang-2 is a context-dependent antagonist/agonist. Therefore, we investigated the
      role of the EC-selective phosphatase, human protein tyrosine phosphatase beta
      (HPTPbeta), in regulating Tie2 activity. METHODS AND RESULTS: siRNA silencing of
      HPTPbeta enhanced Ang-1 and Ang-2-induced Tie2 phosphorylation at 10 min (2.5
      fold, P < 0.001; and 1.8-fold, P < 0.05, respectively). The cell survival
      response to Ang-1, but not Ang-2, was enhanced by HPTPbeta silencing as measured
      by flow cytometry (0.85-fold to 0.66-fold, P < 0.05) and ELISA (0.88-fold to 0.53
      fold, P < 0.01). Hypoxia, which upregulated HPTPbeta expression in endothelial
      cells, impaired Ang-1-induced Tie2 phosphorylation. CONCLUSIONS: These results
      reveal a novel role for HPTPbeta in modulating Ang-1-Tie2 signaling and
      endothelial cell survival.

PMID- 19116767
TI  - Social rank modulates brain arginine vasotocin immunoreactivity in false clown
      anemonefish (Amphiprion ocellaris).
AB  - The brain nanopeptide arginine vasotocin (AVT) and its mammalian homolog arginine
      vasopressin are involved in the regulation of social and reproductive behavior.
      We investigated the relationship between social rank formation and the brain AVT
      system in the false clown anemonefish (Amphiprion ocellaris), which forms a
      social rank that leads to sex differentiation in higher-ranked individuals. Tanks
      of three sexually immature fish were kept for 90 days and each fish's behavior
      was observed once a month. The social rank of each individual was distinguishable
      by behavior, but gonadosomatic index (GSI) did not differ significantly. The
      number of AVT neurons in the magnocellular layer in the preoptic area (POA)
      increased in subordinate individuals and declined with increasing hierarchical
      dominance. These results suggest that social rank formation modulates AVT
      production in the brain of the clown anemonefish and may influence their later
      sex differentiation.

PMID- 19116769
TI  - Effect of N oxyanions on anaerobic induction of nitrate reductase in subcellular
      fractions of Bradyrhizobium sp. (Lupinus).
AB  - Anaerobic induction of nitrate reductase in subcellular fractions of
      Bradyrhizobium sp. strain USDA 3045 showed fivefold increase of the enzyme
      activity in spheroplasts, considered as the source of intact-membrane-bound
      nitrate reductase, within a 3 h time frame after nitrate addition. Such a
      dynamics was confirmed at the protein level, with antibodies specific to membrane
      bound nitrate reductase. Nitrate reductase activity in the periplasm was one
      order of magnitude lower and significant only at initial 3 h of induction, within
      a narrow range of nitrate added. Nitrite induced the membrane-bound nitrate
      reductase at least 70% as effectively as nitrate, as judged from its activity
      pattern and Western blot analysis. The limited ability of Bradyrhizobium sp. to
      dissimilate > or =5 mM nitrate is not due to direct inhibition of respiratory
      nitrate reductase by accumulated nitrite. Moreover, a synergistic induction of
      membrane-bound nitrate reductase by nitrate and nitrite was indicated due to a
      twofold higher protein synthesis after simultaneous addition of these N oxyanions
      than when they were given separately.

PMID- 19116768
TI  - Induction of phase II enzymes and hsp70 genes by copper sulfate through the
      electrophile-responsive element (EpRE): insights obtained from a transgenic
      zebrafish model carrying an orthologous EpRE sequence of mammalian origin.
AB  - We have evaluated the homology of the electrophile-responsive element (EpRE) core
      sequence, a binding site for the Nrf2 transcription factor, in the proximal
      promoters of the mouse and zebrafish glutathione-S-transferase (gst), glutamate
      cysteine ligase catalytic subunit (gclc) and heat shock protein 70 (hsp70) genes.
      The EpRE sites identified for both species in the three analyzed genes showed a
      high similarity with the putative EpRE core sequence. We also produced a
      transgenic zebrafish model carrying a transgene comprised of the luciferase (luc)
      reporter gene under transcriptional control of a mouse EpRE sequence. This
      transgenic model was exposed to copper sulfate, and the reporter gene was
      significantly activated. The endogenous gst, gclc and hsp70 zebrafish genes were
      analyzed in the EpRE-Luc transgenic zebrafish and showed an expression pattern
      similar to that of the reporter transgene used. Our results demonstrate that EpRE
      is conserved between mouse and zebrafish for detoxification-related genes and
      that the development of genetically modified models using this responsive element
      to drive the expression of reporter genes can be an important tool in
      understanding the action mechanism of aquatic pollutants.

PMID- 19116770
TI  - Knowledge, attitudes, and perceptions of pharmacists to adverse drug reaction
      reporting in Iran.
AB  - OBJECTIVE: Adverse Drug Reactions (ADRs) are a major cause of patient morbidity
      and mortality. Spontaneous reporting of ADRs remains the cornerstone of
      pharmacovigilance and is important in maintaining patient safety. In order to
      determine whether our pharmacovigilance system could be improved, and identify
      reasons for under-reporting, a study to investigate the role of pharmacists in
      ADR reporting was performed in Shiraz. SETTING: The pharmacies in Shiraz, capital
      of Fars province in Iran. METHODS: A questionnaire was prepared to investigate
      knowledge and attitude of pharmacists regarding ADR reporting. The questionnaire
      was given to 200 pharmacists who participated in a pharmacist association
      meeting. MAIN OUTCOMES MEASURED: The knowledge of pharmacovigilance practice,
      reasons for not reporting ADR, and perceptions of the Iranian pharmacists on
      pharmacovigilance practice were evaluated. RESULTS: The response rate was 55% (n
      = 110). 29% of the respondents were not aware of the Iranian Pharmacovigilance
      Center. More than half of those responding felt that ADR reporting should be
      voluntary, while 26% felt it was a professional obligation. As for the purposes
      of ADR reporting scheme, 60% of the pharmacists falsely believed that monitoring
      ADR spontaneous reports aims at measuring the incidence of ADR. 42% of the
      pharmacists indicated that they have suspected an ADR without reporting it. Doubt
      about causality was the major reason for not reporting an ADR. Although our ADR
      center states that all suspected reactions to any drug on the market must be
      reported, only 17% of the respondents seemed to be aware of this responsibility.
      CONCLUSION: Our pharmacists have little knowledge regarding the operation,
      purposes, and usefulness of ADR spontaneous reporting system. However, education
      and training will be important in maintaining and increasing ADR reports from
      pharmacists.

PMID- 19116771
TI  - Serologic detection of coccidioidomycosis antibodies in northeast Brazil.
AB  - Coccidioidomycosis is a systemic infection caused by Coccidioides spp. The
      disease is endemic in Brazil but its incidence is underreported as it is not a
      notifiable disease. This article presents the results of a serologic survey
      carried out with 229 volunteers in northeast Brazil by the immunodiffusion (ID)
      test with commercial Coccidioides spp. antigens. The commercial ID test detected
      15 individuals without clinical diagnosis of the disease and two individuals in
      treatment for coccidioidomycosis. Regarding the epidemiological data, most of the
      positive individuals were male, between 18 and 65 years of age and were engaged
      in armadillo hunting. Three women who had never participated in armadillo hunts
      also displayed positive results for coccidioidal antibodies. Besides armadillo
      hunts, exposure to environmental dust in endemic areas may account for the
      serologic response detected in the study. The data from this study suggest the
      importance of performing epidemiological surveys for coccidioidomycosis in order
      to understand the prevalence of this disease in Brazil.

PMID- 19116772
TI  - Cloning and primarily function study of two novel putative N5-glutamine
      methyltransferase (Hemk) splice variants from mouse stem cells.
AB  - Methylation is one of epigenetic mechanisms regulating gene expression. The
      methylation pattern is determined during embryogenesis and passed over to
      differentiating cells and tissues. Beginning with the ESTs which were highly
      expressed in undifferentiated human ES cells and using homology research in mouse
      dbEST database, we cloned two novel putative (N (5))-glutamine methyltransferase
      (Hemk) splice variants termed mHemk1 and mHemk2 (Genbank accession number
      AY456393 and AY583759). Sequence analysis revealed that mHemk1 and mHemk2 cDNAs
      are 1,792 bp and 1,696 bp in length respectively. The deduced proteins have 214
      amino acid residues (mHemk1) and 138 residues (mHemk2) in length and both share
      significant homology with (N (5))-glutamine methyltransferase (Hemk proteins) in
      database. Northern blot and RT-PCR analysis showed that mHemk mRNAs were
      abundantly expressed in undifferentiated ES cells, testis and brain, weakly
      expressed in differentiated ES cells and kidney, and not expressed in muscle,
      heart, placenta, pancreas, lung and stomach. Immunohistochemical analysis further
      revealed that the protein was most abundant in undifferentiated ES cells. The
      green fluorescent protein produced by pEGFP-C3/mHemk1 was detected mainly in the
      nucleus of COS7 cell lines after 24 h post-transfection. RNA interference (RNAi)
      mediated knock-down method was established. Cell cycle analysis suggests that the
      cell proliferation decreases after RNAi with mHemk1. In vitro bioactivity assay
      showed that no evidence for a DNA adenine-methyltransferase activity was
      detected. The accumulating functional information from Hemk homology proteins in
      bacteria and yeast suggests that it may be an uncharacterized new mammalian N(5)
      glutamine methyltransferase.

PMID- 19116773
TI  - Purification and characterization of the cold-active alkaline protease from
      marine cold-adaptive Penicillium chrysogenum FS010.
AB  - An extracellular cold-active alkaline serine protease from Penicillium
      chrysogenum FS010 has been purified. The purification procedure involved:
      ammonium sulfate precipitation, DEAE ion-exchange chromatography and sephadex G
      100 gel chromatography. SDS-PAGE of the purified enzyme indicated a molecular
      weight of 41,000 +/- 1,000 Da. The protease is stable in a pH range of 7.0-9.0
      and has a maximum activity at pH 9.0. Compared with other industrial proteases,
      the enzyme shows a high hydrolytic activities at lower temperatures and a high
      sensitivity at a temperature over 50 degrees C. The isoelectric point of the
      enzyme is approximate to 6.0. Enzymatic activity is enhanced by the addition of
      divalent cations such as Mg(2+) and Ca(2+) and inhibited by addition of Cu(2+)and
      Co(2+). PMSF and DFP are its specific inhibitors. The application of the cold
      active alkaline protease is extremely extensive, and widely used in detergents,
      feed, food, leather and many other industries.

PMID- 19116774
TI  - Perilipin A and the control of triacylglycerol metabolism.
AB  - Perilipin A is the most abundant protein associated with the lipid droplets of
      adipocytes and functions to control both basal and stimulated lipolysis. Under
      basal or fed conditions, perilipin A shields stored triacylglycerols from
      cytosolic lipases, thus promoting triacylglycerol storage. When catecholamines
      bind to cell surface receptors to initiate signals that activate cAMP-dependent
      protein kinase (PKA), phosphorylated perilipin A facilitates maximal lipolysis.
      Mutagenesis studies have revealed that central sequences of moderately
      hydrophobic amino acids are required to target nascent perilipin A to lipid
      droplets and provide an anchor into the hydrophobic environment of lipid
      droplets. Sequences of amino acids in the unique carboxyl terminus of perilipin A
      and those in amino terminal sequences flanking the first hydrophobic stretch are
      required for the barrier function of perilipin A in promoting triacylglycerol
      storage. Site-directed mutagenesis studies of serine residues within six PKA
      consensus sites of perilipin A reveal functions for phosphorylation of at least
      three of the sites. Phosphorylation of one or more of the serines within three
      amino terminal PKA sites is required to facilitate hormone-sensitive lipase
      access to lipid substrates. Phosphorylation of serines within two carboxyl
      terminal sites is also required for maximal lipolysis. Phosphorylation of serine
      492 (site 5) triggers a massive remodeling of lipid droplets, whereby large peri
      nuclear lipid droplets fragment into myriad lipid micro-droplets that scatter
      throughout the cytoplasm. We hypothesize that perilipin A binds accessory
      proteins to provide assistance in carrying out these functions.

PMID- 19116775
TI  - The role of alpha-synuclein in brain lipid metabolism: a downstream impact on
      brain inflammatory response.
AB  - Alpha-synuclein (Snca) is an abundant small cytosolic protein (140 amino acids)
      that is expressed in the brain, although its physiological role is poorly
      defined. Consistent with its ubiquitous distribution in the brain, we and others
      have established a role for Snca in brain lipid metabolism and downstream events
      such as neuroinflammation. In astrocytes, Snca is important for fatty acid uptake
      and trafficking, where its deletion decreases 16:0 and 20:4n-6 uptake and alters
      targeting to specific lipid pools. Although Snca has no impact on 22:6n-3 uptake
      into astrocytes, it is important for its targeting to lipid pools. Similar
      results for fatty acid uptake from the plasma are seen in studies using whole
      mice coupled with steady-state kinetic modeling. We demonstrate in gene-ablated
      mice a significant reduction in the incorporation rate of 20:4n-6 into brain
      phospholipid pools due to reduced recycling of 20:4n-6 through the ER-localized
      long-chain acyl-CoA synthetases (Acsl). This reduction results in a compensatory
      increase in the incorporation rate of 22:6n-3 into brain phospholipids. Snca is
      also important for brain and astrocyte cholesterol metabolism, where its deletion
      results in an elevation of cholesterol and cholesteryl esters. This increase may
      be due to the interaction of Snca with membrane-bound enzymes involved in lipid
      metabolism such as Acsl. Snca is critical in modulating brain prostanoid
      formation and microglial activities. In the absence of Snca, microglia are
      basally activated and demonstrate increased proinflammatory cytokine secretion.
      Thus, Snca, through its modulation of brain lipid metabolism, has a critical role
      in brain inflammatory responses.

PMID- 19116776
TI  - Diet-induced alterations in intestinal and extrahepatic lipid metabolism in liver
      fatty acid binding protein knockout mice.
AB  - Liver fatty acid binding protein (L-FABP) is highly expressed in both enterocytes
      and hepatocytes and binds multiple ligands, including saturated (SFA),
      unsaturated fatty acids (PUFA), and cholesterol. L-fabp (-/-) mice were protected
      against obesity and hepatic steatosis on a high saturated fat (SF), high
      cholesterol "Western" diet and manifested a similar phenotype when fed with a
      high SF, low cholesterol diet. There were no significant differences in fecal fat
      content or food consumption between the genotypes, and fatty acid (FA) oxidation
      was reduced, rather than increased, in SF-fed L-fabp (-/-) mice as evidenced by
      decreased heat production and serum ketones. In contrast to mice fed with a SF
      diet, L-fabp (-/-) mice fed with a high PUFA diet were not protected against
      obesity and hepatic steatosis. These observations together suggest that L-fabp (
      /-) mice exhibit a specific defect in the metabolism of SFA, possibly reflecting
      altered kinetics of FA utilization. In support of this possibility, microarray
      analysis of muscle from Western diet-fed mice revealed alterations in genes
      regulating glucose uptake and FA synthesis. In addition, intestinal cholesterol
      absorption was decreased in L-fabp (-/-) mice. On the other hand, and in striking
      contrast to other reports, female L-fabp (-/-) mice fed with low fat, high
      cholesterol diets gained slightly less weight than control mice, with minor
      reductions in hepatic triglyceride content. Together these data indicate a role
      for L-FABP in intestinal trafficking of both SFA and cholesterol.

PMID- 19116779
TI  - The Work Disability Prevention CIHR Strategic Training Program: program
      performance after 5 years of implementation.
AB  - INTRODUCTION: The Work Disability Prevention (WDP) Canadian Institutes of Health
      Research (CIHR) Strategic Training Program was developed in 2001 and is a unique
      program in the world. The main objective of this program is to help future
      researchers develop transdisciplinary knowledge, skills and attitudes regarding
      WDP. The purpose of this paper is to present a descriptive portrait of the
      program's performance over the past 5 years, as well as the trainees' and
      alumni's perspectives on the WDP CIHR Training Program. METHODS: Data on the
      program's performance were collected from documents in the program records. The
      trainees' opinions on the WDP training program were obtained through focus groups
      and telephone interviews. The data collected were compiled and divided into
      themes to summarize the qualitative findings pertaining to each question.
      RESULTS: From 2003 to 2007, five successive summer sessions have been offered,
      involving 44 high-caliber applicants from nine countries, 34 mentors and
      collaborators, 29 guest speakers and 15 stakeholders. Overall, trainees
      appreciated the networking, the opportunity to interact with people from
      different disciplines and countries, the openness, and the international
      perspective and uniqueness of the program. The least appreciated aspects
      concerned mainly the e-learning course, evaluations and information on optional
      courses. The coordination and logistics were judged appropriate and several
      topics were suggested to improve the program quality. CONCLUSION: In general, the
      program implementation went well, with good participation from mentors, speakers
      and stakeholders; the program was appreciated by the trainees and alumni. This
      paper underscores the importance of the international perspective, the
      transdisciplinarity and the scientific networking established through the
      program.

PMID- 19116777
TI  - Why lipids are important for Alzheimer disease?
AB  - Several lines of evidence suggest that dysregulated lipid metabolism may
      participate in the pathogenesis of Alzheimer's disease (AD). Epidemiologic
      studies suggest that elevated mid-life plasma cholesterol levels may be
      associated with an increased risk of AD and that statin use may reduce the
      prevalence of AD. Cellular studies have shown that the levels and distribution of
      intracellular cholesterol markedly affect the processing of amyloid precursor
      protein into A beta peptides, which are the toxic species that accumulate as
      amyloid plaques in the AD brain. Most importantly, genetic evidence identifies
      apolipoprotein E, the major cholesterol carrier in the central nervous system, as
      the primary genetic risk factor for sporadic AD. In humans, apoE exists as three
      major alleles (apoE2, apoE3, and apoE4), and inheritance of the apoE4 allele
      increases the risk of developing AD at an earlier age. However, exactly how apoE
      functions in the pathogenesis of AD remains to be fully determined. Our studies
      have identified that the cholesterol transporter ABCA1 is a crucial regulator of
      apoE levels and lipidation in the brain. Deficiency of ABCA1 leads to the loss of
      approximately 80% of apoE in the brain, and the residual 20% that remains is
      poorly lipidated. Several independent studies have shown this poorly lipidated
      apoE increases amyloid burden in mouse models of AD, demonstrating that apoE
      lipidation by ABCA1 affects key steps in amyloid deposition or clearance.
      Conversely, robust overexpression of ABCA1 in the brain promotes apoE lipidation
      and nearly eliminates the formation of mature amyloid plaques. These studies show
      that the lipid binding capacity of apoE is a major mechanism of its function in
      the pathogenesis of AD, and suggest that increasing apoE lipidation may be of
      therapeutic importance for this devastating disease.

PMID- 19116780
TI  - Neomodern insecurity in Haiti and the politics of asylum.
AB  - The term 'asylum' has a dual connotation that generates opposing but related
      forms of intervention: providing sanctuary and protection vs. imposing
      confinement and quarantine. The proliferation of "neomodern insecurity"-
      intrastate violence and the specter of transnational terrorism, arising within
      many postcolonial, postauthoritarian and postsocialist states--generates
      intervention practices that reflect the dual connotations of asylum. In fragile
      states like Haiti, national insecurity (ensekirite) often results in the flight
      of traumatized populations across and within national borders. For these
      individuals, 'asylum' connotes the attainment of political recognition and
      inclusion outside Haiti's space of ensekirite. Ironically, these vulnerable
      persons may be viewed as threats to the nations they seek to enter. In so-called
      secure states like the United States, the threat of insecurity often engenders
      interventions to contain, manage and rehabilitate states of disorder, as well as
      their disordered subjects. By chronicling the case of a young Haitian refugee who
      sought asylum in the United States, was detained and then repatriated after
      manifesting the disordered signs of insecurity, I argue that the Haitian trope of
      ensekirite captures and prefigures the subjective experience of neomodernity, one
      for which there is no asylum.

PMID- 19116781
TI  - A cluster randomized controlled trial of an adolescent HIV prevention program
      among Bahamian youth: effect at 12 months post-intervention.
AB  - Behavioral interventions based on the Protection Motivation Theory (PMT) have
      been demonstrated to reduce HIV risk behavior among mid- and older adolescents in
      different settings across the globe but have not been evaluated among Caribbean
      nations and have received limited evaluation among pre-adolescents. To determine
      (1) the effectiveness among pre-adolescents in The Bahamas of a PMT-based HIV
      prevention program "Focus on Youth in the Caribbean" (FOYC) and (2) the role of
      the targeted PMT constructs in intervention effect. 1,360 sixth grade youth (10
      11 years of age) from 15 urban schools in New Providence, The Bahamas were
      randomized by school to receive either FOYC or a control condition. Data
      collected at baseline, 6 and 12 months post intervention were analyzed. A five
      step scheme was used to assess sexual behavior progression, ranging from "1" = "a
      virgin without intention to have sex" to "5" = "having sex without a condom".
      Group-based trajectory analysis was utilized in assessing the program effect. Two
      sexual behavior progression patterns were detected: slow progressors and quick
      progressors. Receiving FOYC reduced the likelihood for adolescents to become
      quick progressors (adjusted OR = 0.77, 95% CI: 0.64-1.00). The observed
      effectiveness was especially impacted by a subset of the targeted PMT constructs.
      FOYC effectively delays sexual risk among Bahamian pre-adolescents. The group
      based trajectory analysis provides an analytical approach for assessing
      interventions among adolescents with low rates and diverse progression patterns
      of sexual activity.

PMID- 19116782
TI  - HIV services utilization in Los Angeles County, California.
AB  - Recipients of HIV/AIDS prevention services in Los Angeles County California were
      surveyed in 2004 by 220 HIV prevention service provider staff from 51 agencies
      funded by the Office of AIDS Programs and Policy. This resulted in 2,102 usable
      surveys for cluster analysis purposes. This Countywide Risk Assessment Survey
      assessed demographics, sexual history, substance use, perceptions regarding
      HIV/AIDS, and use of 18 different services at both the agency administering the
      survey and at other agencies. The 36 types of service use data were subjected to
      a cluster analysis that found five clusters. These service pattern clusters
      differed from each other on proportion HIV positive, HIV testing history, history
      of abuse, education, type of residence, type of funding, intervention type, and
      ethnicity. The analysis also suggests that domestic violence services
      availability and utilization should be examined more thoroughly in the future for
      HIV infected/affected populations.

PMID- 19116784
TI  - UGT2B7 is not expressed in normal breast.

PMID- 19116785
TI  - Preventing burnout in mental health workers at interpersonal level: an Italian
      pilot study.
AB  - This pilot study longitudinally evaluated the effectiveness of an intervention
      aimed at preventing burnout syndrome through the improvement of interpersonal
      relationship management among Italian mental health workers employed in both
      public and private services. Indeed, previous findings and a large part of the
      target group stated that the interpersonal relationship was one of the most
      important sources of stress at work. The results showed positive effects (i.e. a
      reduction of the level of Depersonalization), both at the end of training
      activities and at the follow-up. Since we did not include any control group, the
      results of this study had to be considered with caution and should be confirmed
      by future research.

PMID- 19116786
TI  - Sellar and suprasellar mixed germ cell tumor mimicking a pituitary adenoma.
AB  - Germ cell tumors (GCT) are a heterogeneous group of lesions whose origin is not
      well established. Several cases of primary intrasellar germinomas have been
      reported, however non-germinomatous GCT have rarely been described. We report the
      case of a young adult male patient with a mixed GCT that presented with a sellar
      tumor with suprasellar extension. The patient seeked medical attention because of
      seizures and magnetic resonance imaging evidenced a tumor of the sellar region.
      Hyperprolactinemia was also present and dopamine agonist therapy was started. As
      there was a rapid tumor growth and the patient had concomitant central diabetes
      insipidus and elevated testosterone levels, a GCT was suspected and confirmed by
      elevated serum concentration of beta-human chorionic gonadotrophin. Patient
      underwent surgical resection of the tumor and histopathological examination
      confirmed the diagnosis of a mixed GCT. Chemotherapy was initiated, followed by
      conventional radiotherapy. In conclusion, although pituitary adenomas respond for
      the vast majority of sellar tumors, concomitant symptoms such as central diabetes
      insipidus and rapid tumor growth should raise the suspicion of a diverse
      diagnosis. The present report intend not only to show a rare case of sellar and
      suprasellar mixed GCT but also to remind clinicians that if laboratory findings
      do not fit into patient's diagnosis (such as high testosterone levels in our
      patient), then the diagnosis should be reviewed.

PMID- 19116787
TI  - Normal parathyroid hormone levels in a diabetic patient with parathyroid adenoma.
AB  - OBJECTIVE: The incidence of diabetes mellitus in patients with primary
      hyperparathyroidism and, conversely, primary hyperparathyroidism in diabetic
      patients are approximately threefold higher than the respective expected
      prevalence in the general populace. The diagnosis is straightforward when the
      patient presents hypercalcemia and inappropriately elevated serum parathyroid
      hormone (PTH) levels. We report a case of parathyroid adenoma in a diabetic
      patient with persistent hypercalcemia and normal PTH levels. PATIENT: A 50-year
      old female patient who was referred to our outpatient clinic presented with
      persistent hypercalcemia (serum Ca levels between 10.5 and 11 mg/dl) with a
      normal serum intact PTH level of 46.1 pg/ml. Her blood pressure was 120/80 mmHg,
      and she was being treated with antihypertensive therapy. Her HbA1c was 7.2%, and
      her triglycerides were in the normal range. A bone densitometry exam revealed
      osteopenia of radius -1.39, femoral neck -1.39, and the total hip -1.04. A neck
      ultrasound revealed a mass of 13 mm next to the inferior and posterior of the
      right thyroid lobe. A dual phase Tc-99m-sestamibi scan revealed an area of
      increased uptake in the same region, which is indicative of a parathyroid
      adenoma. The parathyroid adenoma was removed, which resulted in the achievement
      of normocalcemia. CONCLUSION: Diabetic patients should be evaluated for
      hyperparathyroidism as associated hypertension can complicate the course of the
      disease. These patients should be evaluated for primary hyperparathyroidism when
      they exhibit persistent hypercalcemia and when clinical suspicion is aroused even
      if the serum PTH levels are within the normal range.

PMID- 19116789
TI  - Isolated congenital ossicular anomalies.
AB  - CONCLUSIONS: Isolated congenital ossicular anomalies are diverse. Our proposed
      modified Teunissen and Cremers classification will be helpful for the evaluation
      of congenital ossicular anomalies as well as the prediction of surgical outcome.
      OBJECTIVES: The aim of this study was to describe isolated congenital ossicular
      anomalies encountered in patients who have normal eardrums and to evaluate their
      surgical outcome based on their classification. PATIENTS AND METHODS: A total of
      78 patients (94 ears) with congenital ossicular anomalies were reviewed. The
      preoperative and postoperative audiological findings, surgical findings, and
      temporal bone CT results were analyzed. RESULTS: Twenty-one types of ossicular
      anomalies were identified in this study. A stapes footplate fixation was the most
      common anomaly and this was usually bilateral. However, the anomalies that were
      associated with the incus and malleus were usually unilateral. The congenital
      ossicular anomalies were classified into five types according to the status of
      the stapes footplate. Using this modification of a prior classification system,
      the more severe anomalies of the stapes footplate could be identified, and the
      worst postoperative hearing result could be predicted.

PMID- 19116788
TI  - Selective transcriptional regulation of aromatase gene by vitamin D,
      dexamethasone, and mifepristone in human glioma cells.
AB  - The human aromatase gene (CYP19A1) is controlled by multiple promoters that give
      rise to different aromatase transcripts. Its regulation has been studied in cells
      from multiple origins, including placenta, bone, adipose tissue, and breast
      cancer. However, little is known about its regulation in cells from neural
      origin. We assessed whether vitamin D, dexamethasone, and the glucocorticoid
      receptor antagonist mifepristone regulate the aromatase gene in human glioma,
      neuroblastoma, and breast cancer cells. The results show that these compounds
      enhance the activity of different aromatase promoters in glioma cells, but not in
      neuroblastoma and breast cancer cells. Vitamin D increased the expression of I.3,
      I.7, and I.4 aromatase transcripts and induced de novo expression of the I.6
      transcript; dexamethasone increased the expression of I.4, PII, and I.3
      transcripts and mifepristone increased the expression of PII and I.3 aromatase
      transcripts. The cell specific regulation of CYP19A1 by vitamin D, dexamethasone,
      and mifepristone opens the possibility for cellular selective modulation of
      estrogen biosynthesis within the brain.

PMID- 19116790
TI  - The association of codeine, macrocytosis and bilateral sudden or rapidly
      progressive profound sensorineural deafness.
AB  - CONCLUSIONS: Codeine shows a similar association with profound deafness to other
      opiates. Good cochlear implant outcomes suggest a sensory disorder. Although
      macrocytosis could be due to confounding factors, the lack of other consistent
      findings may signify a vascular pathology. OBJECTIVES: To describe a series of
      patients identified as codeine users after referral for cochlear implantation.
      PATIENTS AND METHODS: This was a retrospective case series review. Patients were
      identified by the senior audiologist. Information regarding mode of onset of
      deafness, past medical history, drug and alcohol history, investigations and
      audiological outcomes following cochlear implantation was collected from hospital
      records and patient questionnaires. RESULTS: Ten patients were included in the
      study. All patients had taken codeine phosphate and paracetamol in combination
      for several years, usually at greater than recommended daily dose. All patients
      presented with sudden or rapidly progressive bilateral deafness. All patients had
      a significant macrocytosis at the time of deafness (mean cell volume (MCV): mean
      115 fL; range 105-132 fL). No other investigation was consistently abnormal. Four
      patients had a history of alcoholism. Seven patients had abnormal liver function
      tests. Patients usually performed well with cochlear implants (CUNY sentence
      scores without lip reading >90% in 9 of 10 patients).

PMID- 19116791
TI  - Synaptic alterations in the medial geniculate bodies and the inferior colliculi
      in Alzheimer's disease: a Golgi and electron microscope study.
AB  - CONCLUSION: The neuronal loss and the alteration of the synapses in the medial
      geniculate bodies and the inferior colliculi may be involved in the impairment of
      communication and symbolic sound perception, which is noticed even in the early
      stages of Alzheimer's disease. OBJECTIVES: Alzheimer's disease (AD) is a
      neurodegenerative disorder, causing a progressive decline of intellectual
      faculties, gradual impairment of behavior and social performance, impairment of
      communication and speech eloquence, and various neurological manifestations. We
      attempted to figure out the synaptic alterations in the medial geniculate bodies
      and the inferior colliculi in 12 early cases of Alzheimer's disease, who
      fulfilled the clinical, and laboratory diagnostic criteria of Alzheimer's
      disease. SUBJECTS AND METHODS: For the histological study we applied routine
      neuropathological techniques as well as Bodian staining and rapid Golgi method.
      We proceeded to electron microscopy for the ultrastructural study of synapses and
      dendritic spines. RESULTS: The morphological and morphometric analysis revealed
      substantial neuronal loss and synaptic alterations in the medial geniculate
      bodies as well as in inferior colliculi. Dendritic spines of the polyhedral and
      elongated cells of the medial geniculate bodies were decreased in number.
      Mitochondrial alterations and fragmentation of Golgi apparatus were seen in 15%
      of the neurons of the medial geniculate bodies and in 5% of the neurons of the
      inferior colliculi. Senile plaques and neurofibrillary tangles were not seen in
      either the medial geniculate bodies or the inferior colliculi.

PMID- 19116795
TI  - Cortical activation during optokinetic stimulation - an fMRI study.
AB  - CONCLUSION: Activation of cortical areas related to visual motion processing and
      control of eye movement, and deactivation of parieto-insular vestibular cortices
      (PIVC) were revealed by functional magnetic resonance imaging (fMRI) with small
      field optokinetic stimulation (OKS). The results agreed well with those of
      previous studies, which indicates that the current protocol is reliable enough to
      be used as a clinical examination. OBJECTIVES: To propose an fMRI set-up with OKS
      that is reliable and simple enough to be performed as a clinical test. SUBJECTS
      AND METHODS: Ten right-handed healthy volunteers participated in this study. fMRI
      was used to measure blood oxygen level-dependent (BOLD) signal increases
      (contrast: OKS - rest) and decreases (contrast: rest - OKS) during small-field
      OKS. Functional images were acquired using a standard clinical scanner operating
      at a magnetic field strength of 1.5 T. The data were analyzed by statistical
      parametric mapping (SPM2), and the significance level was set at p<0.001,
      uncorrected. RESULTS: BOLD signal increases were observed in the visual
      association area of both hemispheres (BA19) (MT/V5), primary visual cortex (BA17)
      of the right hemisphere, bilateral superior parietal lobules (BA7), and bilateral
      frontal eye fields (BA6). Decreases of BOLD signals were observed in the PIVC
      bilaterally.

PMID- 19116798
TI  - Commentary on "marital happiness and sleep disturbances in a multi-ethnic sample
      of middle-aged women".

PMID- 19116799
TI  - Relationship quality and CPAP adherence in patients with obstructive sleep apnea.
AB  - The prospective influence of relationship support and conflict on adherence to
      continuous positive airway pressure (CPAP) was examined over the first 3 months
      of CPAP treatment in 42 married, male patients with obstructive sleep apnea
      (OSA). CPAP adherence reports were available for 23 patients. Patient ratings of
      marital conflict predicted average nightly adherence (beta = -0.357, p < .05),
      but ratings of marital support did not predict adherence. Three-month follow-up
      ratings of marital support and conflict, subjective sleepiness, depression, and
      functional impairment were available for 16 patients from the first sample. Six
      additional patients without adherence reports provided baseline and 3-month
      follow-up questionnaire data, which resulted in a total of 22 patients with
      follow-up questionnaire data. Following 3 months of CPAP, patients reported
      decreased marital conflict (d = 0.43, p < .05), sleepiness (d = 1.13, p < .001),
      depression (d = 0.73, p < .001), and functional impairment (d = 1.48, p < .001).
      These findings highlight the importance of evaluating marital conflict for OSA
      patients and suggest marital conflict may be a target for interventions to
      improve CPAP adherence.

PMID- 19116797
TI  - Marital happiness and sleep disturbances in a multi-ethnic sample of middle-aged
      women.
AB  - Previous research suggests that divorced individuals, particularly women, have
      higher rates of sleep disturbances as compared to married individuals. Among the
      married, however, little is known about the association between relationship
      quality and sleep. The present study examined the association between marital
      happiness and self-reported sleep disturbances in a sample of midlife women drawn
      from the Study of Women's Health Across the Nation (SWAN), a multi-site, multi
      ethnic, community-based study (N = 2,148). Marital happiness was measured using a
      single item from the Dyadic Adjustment Scale, and sleep disturbance was assessed
      using 4 items from the Women's Health Initiative Insomnia Rating Scale (WHIIRS).
      After controlling for relevant covariates, maritally happy women reported fewer
      sleep disturbances, with the association evident among Caucasian women and to a
      lesser extent among African American women.

PMID- 19116800
TI  - Characteristics of individuals with insomnia who seek treatment in a clinical
      setting versus those who volunteer for a randomized controlled trial.
AB  - The generalizability of outcome data derived from insomnia clinical trials is
      based largely on the extent to which research volunteers resemble clinical
      patients. This study compared sociodemographic, sleep, psychological, and medical
      characteristics of individuals who volunteered for an insomnia treatment study (n
      = 120) to patients who sought treatment in a clinical setting (n = 106). The
      samples did not differ on most sleep and medical variables, but clinical patients
      had a higher prevalence of mood disorders, greater anxiety and depression
      symptoms, and higher perceived insomnia severity. Differences on psychological
      variables were accentuated by the research selection process. It is suggested to
      minimize exclusion based on psychological comorbidity in order to enhance
      ecological validity of randomized controlled trials of insomnia treatments.

PMID- 19116801
TI  - Sensory hypersensitivity as a contributing factor in the relation between sleep
      and behavioral disorders in normal schoolchildren.
AB  - Despite growing interest in the relationship between sleep disturbances and
      behavioral disorders-specifically, symptoms of attention deficit/hyperactivity
      disorder (ADHD) in children-the underlying structure of this relationship is
      poorly understood. The aim of the study was to explore the contribution of
      sensory hypersensitivity to this relationship. Parents of 56 schoolchildren
      completed questionnaires reporting sleep habits, behavior, and sensory
      processing. Significant correlations were found between global scores of all 3
      constructs; however, the relationship between sleep and behavior decreased when
      controlling for sensory processing. Among different sensory modalities, tactile
      sensitivity was a significant predictor for sleep, accounting for 25% of the
      variance, F = 16.30, p < .001; and sensation seeking and tactile sensitivity were
      significant predictors for behavior, accounting for 42% of the variance, F =
      17.56, p < .001. If confirmed by further objective investigation, the results of
      this study suggest that sensory profiles of children with sleep or behavioral
      disorders should be routinely assessed in clinical practice.

PMID- 19116803
TI  - Acupuncture for treating menopausal hot flushes: a systematic review.
AB  - OBJECTIVE: To assess the effectiveness of acupuncture as a treatment option for
      menopausal hot flushes. DESIGN: We have searched the literature using 17
      databases from inception to October 10, 2008, without language restrictions. We
      included randomized clinical trials (RCTs) of acupuncture versus sham
      acupuncture. Their methodological quality was assessed using the modified Jadad
      score. RESULTS: In total, six RCTs could be included. Four RCTs compared the
      effects of acupuncture with penetrating sham acupuncture on non-acupuncture
      points. All of these trials failed to show specific effects on menopausal hot
      flush frequency, severity or index. One RCT found no effects of acupuncture on
      hot flush frequency and severity compared with penetrating sham acupuncture on
      acupuncture points that are not relevant for the treatment of hot flushes. The
      remaining RCT tested acupuncture against non-penetrating acupuncture on non
      acupuncture points. Its results suggested favorable effects of acupuncture on
      menopausal hot flush severity. However, this study was too small to generate
      reliable findings. CONCLUSION: Sham-controlled RCTs fail to show specific effects
      of acupuncture for control of menopausal hot flushes. More rigorous research
      seems warranted.

PMID- 19116805
TI  - Utilisation of patient perspective to validate clinical measures of outcome
      following spinal cord injury.
AB  - PURPOSE: The purpose of this article is to utilise the perspective of persons
      with a spinal cord injury (SCI), gained from focus groups, to validate
      recommended clinical measures of outcome. METHOD: Clinical measures of outcome as
      recommended by Wood-Dauphinee and the SCI Consensus Group were categorised using
      the World Health Organisation's International Classification of Functioning,
      Disability and Health (ICF). These were then cross-referenced to the problems of
      functioning identified by patients in 10 focus groups held in New Zealand as part
      of the International ICF Core Set project. The focus groups were performed
      separately for people in the post-acute situation and in the chronic situation to
      address different experiences since SCI. RESULTS: In the post-acute group, the
      recommended measures of functioning, the Functional Independence Measure (FIM),
      Hospital Anxiety and Depression Scale and Visual Analogue Scale for pain
      correlated well against the focus groups identification of problems of
      functioning. In the chronic group, the short-form Craig Handicap Assessment and
      Reporting Technique (sf-CHART), the SF-12 and the Life Satisfaction Questionnaire
      (LSQ) largely captured the problems of functioning identified. There were some
      categories that were common to both patient groups and were not changed by time
      since SCI. In addition, there were some problems of functioning identified by the
      patient groups that were not covered by the suggested measures. CONCLUSIONS:
      Utilisation of a battery of outcome measures based on a theoretical framework can
      quantify problems of functioning in the SCI population. Although the measures
      suggested by SCI Consensus Group largely capture the problems of functioning,
      other outcome measures have been shown to be more responsive to the changes in
      the SCI population and also incorporate more of the identified problems of
      functioning.

PMID- 19116806
TI  - A review of the definitions of 'recovery' used in prognostic studies on whiplash
      using an ICF framework.
AB  - PURPOSE: The purpose of this article is to review the various definitions of
      recovery used in the prognostic whiplash literature to date, and to evaluate them
      from the framework of the International Classification of Functioning, Disability
      and Health (ICF). METHODS: Reference lists of previous systematic reviews and
      meta-analyses on the topic were reviewed and citations were retrieved. An updated
      Medline search was performed. Recovery rates and the method for operationalising
      recovery were extracted and evaluated for their fit within the ICF model of
      health. Descriptive statistics were calculated and presented. RESULTS: Thirty-one
      independent cohorts were identified. In total, 30 different primary methods for
      defining recovery were described in the sample of literature. Eighty-three
      percent of the primary outcomes fit within the body structure and function domain
      of the ICF. Restricted participation was the second most common domain
      represented, followed by activity limitations. Even within each domain, there is
      wide variability in the cut-off values for dichotomising a group as recovered or
      not. CONCLUSIONS: The wide range of recovery rates reported in the literature can
      be at least partly accounted for by the lack of a standardised definition of
      recovery after acute whiplash. The emphasis on symptoms in the current literature
      neglects other important aspects of health as described by the ICF.

PMID- 19116807
TI  - Restrictions in social participation of young adults with spina bifida.
AB  - PURPOSE: To determine participation restrictions of young adults with spina
      bifida (SB) in relation to health condition and activity limitations. METHOD: A
      total of 179 persons aged 16-25 years and born with SB participated in a cross
      sectional study. The main outcome on four domains of participation (independent
      living, employment, education and partner relationships) was assessed using a
      structured questionnaire. RESULTS: At the mean age of 21 years only 16% were
      living independently, more than one-third of the participants went to special
      secondary education, 53% of those who finished education did not have a regular
      job and 71% did not have a partner. Health condition variables (type of SB,
      hydrocephalus and level of lesion) and to a lesser extent activity limitations
      (wheelchair dependence and incontinence) were significant determinants for having
      participation restrictions. Perceived hindrances in participation included long
      distance transportation (19-36%), accessibility (10-42%), physical impairments
      (22-40%), emotional barriers (20-32%) and financial limits (3-17%). More severe
      SB, defined as hydrocephalus, high level of lesion and wheelchair dependence, was
      related with more experienced hindrances due to long-distance transportation
      accessibility of buildings. CONCLUSIONS: Many young adults with spina bifida
      experience participation restrictions. Severity of SB was negatively related to
      participation. Social integration should be a major focus in the professional
      guidance of youngsters with physical disabilities.

PMID- 19116808
TI  - Factors associated with quality of life in patients with chronic respiratory
      failure due to kyphoscoliosis.
AB  - OBJECTIVES: Patients with chronic respiratory failure due to kyphoscoliosis (CHRF
      KS) constitute a specific population with impaired health-related quality of life
      (HRQL). Thus far, no studies have examined factors related to HRQL. The objective
      of the present study was to identify clinical, functional and exertion-related
      factors associated with HRQL. METHODS: We investigated 27 patients (12 males).
      Respiratory function tests, dyspnea ratings, peripheral and respiratory muscle
      function and exercise testing were performed. The Chronic Respiratory Disease
      Questionnaire (CRDQ) was used to assess HRQL. Bivariate correlations were used to
      investigate the relationships between CRDQ dimensions and the clinical,
      functional and exertion-related characteristics of the study participants.
      RESULTS: The general characteristics of the study sample were as follows: age: 61
      (IQR: 12) years, FVC: 32.6% (IQR: 10.2) and pCO2: 48 mmHg (IQR: 8.7). Peripheral
      muscle strength, dyspnea and exercise capacity were identified as significant
      factors associated with poorer HRQL. The CRDQ dimensions of fatigue and emotional
      function showed greater correlations with the patients' general characteristics.
      Dyspnea CRDQ scores did not correlate with dyspnea in any of the scales used.
      CONCLUSION: Of the various factors examined, dyspnea, exercise capacity and
      peripheral muscle strength have been identified as significant factors associated
      with HRQL in CHRF-KS patients.

PMID- 19116809
TI  - A biopsychosocial perspective on adjustment and quality of life following brain
      tumor: a systematic evaluation of the literature.
AB  - PURPOSE: To systematically evaluate the literature on quality of life and
      adjustment to brain tumor from a biopsychosocial perspective. METHODS: On the
      basis of the cancer and brain injury literature, a biopsychosocial organisational
      framework was initially developed to support an evaluative review of the brain
      tumor literature. This framework consisted of four themes relating to pre-illness
      characteristics, neuropathology, personal appraisals and reactions and social
      support. Electronic searches of Medline, PsycINFO and CINAHL databases identified
      48 empirical studies (1980-2007) that investigated factors associated with
      quality of life or the adjustment of adults with brain tumor. A review of studies
      within each theme appraised these findings and evaluated the quality of
      methodology and extent to which biopsychosocial perspectives have guided
      investigations. RESULTS: Overall, the review identified consistent associations
      between depression, performance status, fatigue and quality of life. Seven
      multivariate studies with strong methodology that adopted a biopsychosocial
      perspective were found. In general, the relationships among pre-illness and brain
      tumor characteristics, psychosocial variables and quality of life were unclear
      and various gaps in the literature emerged. CONCLUSIONS: Empirical findings
      within a biopsychosocial perspective may guide the development and delivery of
      support services for individuals with brain tumor; however, many important areas
      exist for future research.

PMID- 19116810
TI  - Post-concussion symptoms after mild traumatic brain injury: influence of
      demographic factors and injury severity in a 1-year cohort study.
AB  - PURPOSE: To assess the prevalence and variation of post-concussion symptoms
      within the first year after mild traumatic brain injury (TBI), and explore the
      association between injury severity, demographic factors and symptoms. METHODS:
      Prospective study of patients with mild TBI followed up at 3, 6 and 12 months (N=
      96 included, n = 52 attending all follow-ups). Sociodemographic factors, injury
      mechanisms and impact of injury (Glasgow Coma Scale score, Abbreviated Injury
      Severity Score (AIS), Injury Severity Score) were recorded at inclusion. Symptoms
      were reported in the Rivermead Post-Concussion Symptoms Questionnaire (RPQ) at
      the follow-ups. The sumscore of all symptoms in RPQ was calculated for each
      subject. Scores were also calculated separately for the cognitive, physical and
      behavioural symptoms. RESULTS: Twenty-nine subjects met the post-concussion
      syndrome criteria at 3 months, and 22 patients at 6 and 12 months. The cognitive
      symptoms were more prominent than the physical and behavioural symptoms. The
      cognitive and physical symptoms were associated with AIS for the head injury at 3
      months, but not at 12 months. Considerable individual variability in the symptom
      pattern was found, and the subjects who attended only the 3-months follow-up
      reported a lower level of symptoms than those attending all follow-ups.
      CONCLUSIONS: Persistence of symptoms was a considerable problem even 1 year after
      the injury, with cognitive symptoms dominating. More severe AIS scores were
      associated with a higher level of cognitive and physical symptoms at 3 months,
      but not at later follow-ups. Strategies to prevent and treat these symptoms
      should be focussed in clinical practice.

PMID- 19116811
TI  - Histopathological diagnosis of a type vii mucopolysaccharidosis after pregnancy
      termination.
AB  - Type VII mucopolysaccharidosis is a very rare recessive lysosomal storage
      disease. We diagnosed a type VII MPS in a case of severe fetal hydrops after
      pregnancy termination at 23 weeks of gestation. The diagnosis was suspected on
      histopathological examination by the presence of foam cells in many viscera and
      foamy placental Hofbauer cells. Enzyme assay on cultured amniotic cells showed a
      markedly deficient beta-glucuronidase activity, thus confirming the diagnosis.
      This report shows the importance of a precise necropsy diagnosis in nonimmune
      hydrops because of putative implications for genetic counseling and prenatal
      diagnosis in subsequent pregnancies.

PMID- 19116812
TI  - Immunohistochemical expression of p57 in placental vascular proliferative
      disorders of preterm and term placentas.
AB  - P57 protein is implicated in some human imprinting disorders such as hydatiform
      mole and Beckwith-Wiedemann syndrome (BWS), both characterized by mesenchymal and
      vascular placental abnormalities. We investigated p57 immunohistochemical
      expression in placental vascular proliferative disorders of preterm and term
      placentas, including chorangiosis (n = 5), chorangiomatosis (n = 2), chorangiomas
      (n = 7), umbilical cord angioma (n = 1), and placental mesenchymal dysplasia
      (PMD) (n = 7). P57 was expressed in decidua, cytotrophoblast, intermediate
      trophoblast and stromal cells of normal terminal, intermediate and stem villi,
      umbilical cord, chorangiosis, chorangiomatosis, and chorangiomas. In contrast,
      there was a loss of p57 expression in stromal cells of dysplastic stem villi in
      all cases of PMD regardless of whether associated with BWS or not. P57 seems to
      be involved in the pathogenesis of a subset of placental vascular proliferative
      disorders in preterm and term placentas, such as PMD. The loss of p57 expression
      in PMD could be of diagnostic value in helping to distinguish this rare placental
      lesion from its mimickers.

PMID- 19116813
TI  - Cerebellar migration defects in aicardi syndrome: an extension of the
      neuropathological spectrum.
AB  - The Aicardi syndrome is characterized by infantile spasms, corpus callosum
      agenesis, and chorioretinal lacunae and almost exclusively affects females (very
      rarely, 47, XXY males). The crucial genetic mishap likely occurs in the
      postzygotic stage, but the variable clinical phenotype among the approximately
      450 known cases has not been explained. No consistent mutations or deletions
      exist among patients. We encountered a baby girl with early onset infantile
      spasms. She had left-sided cleft lip/palate, costovertebral defects, scoliosis,
      callosal agenesis, and microphthalmia. She expired at the age of 3 months of
      respiratory infection. On autopsy she had thoracic hemivertebrae with rib
      defects, bilateral microphthalmia, microcornea, posterior colobomata,
      abnormalities of the retinal pigment epithelium, absence of normal ganglion cells
      in the retina, gross asymmetry of the brain with cerebral polymicrogyria, total
      callosal agenesis, cerebral subcortical and subependymal nodular heterotopias,
      cerebellar nodular heterotopias, and tegmental/basal unilateral brainstem
      hypoplasia. Cerebellar and retinal migration defects have not been described
      before in Aicardi syndrome and may have had a bearing on this patient's eventual
      outcome.

PMID- 19116814
TI  - Disseminated langerhans cell histiocytosis-related sudden unexpected death in
      infancy.
AB  - Sudden unexpected death in infancy (SUDI) is defined as the sudden and unexpected
      death of an infant aged less than 1 year and comprises a heterogeneous group of
      deaths; in around one-third of cases a definite cause of death is identified at
      autopsy, while almost two-thirds of such deaths will remain unexplained despite a
      careful review of the circumstances of death and a detailed postmortem
      examination. We report a case of SUDI due to previously undiagnosed disseminated
      Langerhans cell histiocytosis (LCH) in a 10-month-old male, a disease
      characterized by a clonal proliferation of dendritic Langerhans cells. The
      diagnosis was established on histological examination, which revealed extensive
      infiltration by LCH of the skin, lymph nodes, thymus, spleen, and lungs. Despite
      a high mortality in disseminated disease, to our knowledge, this is the first
      reported case in the English-language literature of disseminated multisystem
      Langerhans cell disease presenting as SUDI. Furthermore, this case demonstrates
      the importance of routine microscopic tissue sampling in all SUDI, as the
      diagnosis required histological examination of the organs and might have been
      missed had histology not been performed.

PMID- 19116816
TI  - Editorial retraction.

PMID- 19116817
TI  - Plagiarism.

PMID- 19116818
TI  - Letter of apology.

PMID- 19116819
TI  - Adapting and testing the Appraisal of Violent Situation scales.
AB  - The purpose of this study was to test the psychometric properties of a vertical
      version of horizontally oriented three Appraisal of Violent Situation scales that
      elicit women's subjective appraisals of severity, dangerousness, and
      controllability of violence. Construct validity of the vertical scale eliciting
      64 abused women's perceptions of severity of violence experienced was supported
      by a low to modest correlation between that scale and the Severity of Violence
      Against Women Scale. Concurrent validity between the horizontal and vertical
      versions of the scales was demonstrated with a subsample of 26 abused women
      completing both. Results provide preliminary support for the revised scales.

PMID- 19116820
TI  - Examination for sexual assault: evaluating the literature for indicators of women
      centered care.
AB  - This study aimed to assess the extent to which recent peer-reviewed published
      literature on the acute management of sexual assault was women-centered. We
      developed indicators and a framework that operationalized women-centered care
      provision in the context of sexual assault. We then reviewed and evaluated the
      literature in relation to these indicators. A systematic search identified a
      total of 20 relevant articles for inclusion in the analysis. These were published
      in medical journals (65%, 13/20), nursing journals (20%, 4/20), and journals
      targeted toward other health care practitioners (15%, 3/20), and originated from
      the United States (65%, 13/20), the United Kingdom (15%, 3/20), Australia (10%,
      2/20), Spain (5%, 1/20), and Canada (5%, 1/20) between January 2000 and August
      2005. We found little acknowledgment of the inherent tensions faced by sexual
      assault examiners in providing women-centered care. Moreover, absent from most
      articles were discussions of the complexities of consent in sexual assault
      examinations, social justice issues, the need for gender-sensitive training for
      health care providers, and a critical appraisal of colposcopic and DNA
      technologies. Indicators of respect, safety and restoring control, and
      connections to community were present in the majority of articles.

PMID- 19116821
TI  - Enculturation as a condition impacting Korean American physicians' responses to
      Korean immigrant women suffering intimate partner violence.
AB  - We explored how Korean American (KA) physicians in the Los Angeles area respond
      in their medical practice to Korean immigrant women with a history of intimate
      partner violence (IPV). Twenty physicians were recruited and interviewed in
      depth. Grounded theory analyses revealed that KA physicians' responses to IPV
      ranged from denying signs of IPV and trivializing IPV to acknowledging IPV.
      Physician response was related to the degree to which he or she was enculturated
      in mainstream medical practice norms in the United States. We advance current
      knowledge on physicians' IPV screening and intervention practices by exploring
      the practices of KA physicians, in particular.

PMID- 19116822
TI  - Striving to make a difference: health care worker experiences with intimate
      partner violence clients in Tanzania.
AB  - In this article we describe health care workers' (HCWs') experiences and
      perceptions of meeting clients exposed to intimate partner violence (IPV).
      Qualitative content analysis of in-depth interviews from 16 informants resulted
      in four main themes. The first, "internalizing women's suffering and
      powerlessness," describes HCWs' perceptions of violence, relating it to gender
      relations. The second, "caught between encouraging disclosure and lack of support
      tools," refers to views on possibilities for transparency and openness. The
      third, "Why bother? A struggle to manage with limited resources," illustrates the
      consequences of a heavy workload. Last; "striving to make a difference,"
      emphasizes a desire to improve abilities to support clients and advocate for
      prevention.

PMID- 19116823
TI  - Marginality and physical and sexual abuse in women.
AB  - We examine the role of marginality as a social determinant of physical and sexual
      abuse in women. In this study of a community sample of 568 women of reproductive
      age, and women with a history of physical and sexual abuse reported significantly
      more marginality than women without a prior history of abuse. An inverse
      relationship between socioeconomic status (SES) and marginality existed. Sexual
      abuse initially experienced in childhood had a more profound impact on
      marginality in women than when the abuse initially occurred in adolescence or
      adulthood. Early identification of abused women in clinical practice may help to
      prevent further marginality and adverse health outcomes.

PMID- 19116824
TI  - Powerlessness, anger, and stress in African American women: implications for
      physical and emotional health.
AB  - African American women find themselves at a high risk of experiencing feelings of
      powerlessness associated with socioeconomic disparities rooted in a history of
      racism and sexism. The authors present a conceptual model that discusses
      powerlessness as a significant variable that contributes to the experience of
      anger and stress in African American women, and consequently to the adverse
      health consequences of such anger and stress. The authors review the current
      literature as well as census and health statistics to discern critical
      historical, social, and cognitive aspects of powerlessness and anger in African
      American women. Implications for practitioners are addressed.

PMID- 19116825
TI  - "Never my daughters": a qualitative study regarding attitude change toward female
      genital cutting among Ethiopian and Eritrean families in Sweden.
AB  - To explore attitudes toward female genital cutting (FGC) in a migration
      perspective, qualitative interviews were conducted with men and women from
      Ethiopia and Eritrea in Sweden. We found firm rejection of all forms of FGC and
      absence of a guiding motive. Informants failed to see any meaning in upholding
      the custom. We conclude that children of Ethiopian or Eritrean parents resident
      in Sweden run little risk of being subjected to FGC. A societal structure
      prepared to deal with suspected cases of FGC with a high level of alertness
      should be combined with a healthy sceptical attitude toward exaggerations of risk
      estimates.

PMID- 19116826
TI  - Strategies used by rural women to stop, avoid, or escape from intimate partner
      violence.
AB  - In this mixed methods study we examined the strategies rural women use to deal
      with intimate partner violence (IPV). The Intimate Partner Violence Strategies
      Index (IPVSI) was used to analyze results from a sample of 43 rural women who had
      left abusive partners. Qualitative interviews then were conducted with a
      different sample of nine rural women to explore their perspectives about the
      findings and their impressions of the influence of rural culture and context on
      women's experiences of IPV. Findings exposed the degree to which social control
      acts as a key determinant of health for rural women exposed to IPV.

PMID- 19116828
TI  - Prenatal exposures to LTP-patterned magnetic fields: quantitative effects on
      specific limbic structures and acquisition of contextually conditioned fear.
AB  - Weak (<1 microT) complex magnetic fields (CMFs) may exert their behavioral
      influences through the hippocampus by resonating by accident or design with
      intrinsic electrical patterns. Rats were exposed prenatally to one of four
      intensities of a CMF (either <5 nanoTesla [nT], 10-50 nT, 50-500 nT, or 500-1000
      nT) designed to interact with the process of Long-Term Potentiation (LTP) in the
      hippocampus. Rats then underwent testing in the forced swim, open field, and fear
      conditioning procedures. The cell densities of all amygdaloid nuclei, specific
      hypothalamic structures, and the major regions of the hippocampus were
      quantified. Results showed that acquisition of conditioned fear was strongly
      inhibited in animals exposed to LTP-CMFs. Rats exposed to intensities above 10 nT
      showed decreased cell density in the CA2 fields of the hippocampus; more neurons
      were present in the CA1 fields of rats exposed to the 10-50 nT intensities
      compared to all other groups. A decrease in cell density in the medial preoptic
      nucleus was linearly dependent on field intensity. In the forced-swim test,
      swimming was decreased in rats that had been exposed to low (10-50 nT) and medium
      intensity (50-500 nT) LTP-CMFs in a manner consistent with monoamine modulation.
      In the open field, exposed rats were indistinguishable from controls. These
      findings support the hypothesis that continuous exposure during prenatal
      development to CMFs designed to simulate intrinsic LTP within the hippocampus can
      affect adult behaviors specific to this structure and produce quantitative
      alterations in neuronal density.

PMID- 19116827
TI  - Violence and women's psychological distress after birth: an exploratory study in
      Italy.
AB  - Our aim in conducting this study was to analyze the relationships between
      violence and maternal psychological distress 8 months after a birth, taking into
      account other important psychosocial factors, known to be associated both with
      violence and with new mothers' mental health. A total of 352 women responded to a
      questionnaire after the birth at a maternity hospital in northern Italy, and 292
      also participated in a telephone interview 8 months later. We evaluated
      psychological distress with the General Health Questionnaire (GHQ), and partner
      and family violence with a 28-item scale. Eight months postpartum, 5% of women
      showed high psychological distress; 10% were currently experiencing violence from
      the partner or another family member. After adjustment for covariates, the odds
      ratio for depressive symptoms was 13.74 for women experiencing violence. We
      believe that these results provide support for the important role of violence in
      postpartum maternal psychological distress.

PMID- 19116829
TI  - Neural precursor cell lines promote neurite branching.
AB  - Schwann cells and primary progenitor cells improve regeneration across peripheral
      nerve defects. This study examined the impact of immortalized neural precursor
      cells on regeneration of rat nerve defects. Across 10-mm gaps, neuromas formed
      without neural cables with C17.2- or RN33B-transplanted cells, but neural cables
      formed across 5-mm gaps seeded with RN33B cells. In vitro, dorsal root ganglia
      neurites elongated across Schwann and RN33B cells; RN33B cells induced neurite
      branching with shorter total outgrowth. Neural cable formation in vivo was likely
      determined by the balance of guidance and branch-inducing factors secreted by
      Schwann and transplanted precursor cells.

PMID- 19116830
TI  - Adolescent and adult male spontaneous hyperactive rats (SHR) respond differently
      to acute and chronic methylphenidate (Ritalin).
AB  - Eight groups of male adolescent and adult spontaneous hyperactive rats (SHR) were
      used in a dose response (saline, 0.6, 2.5, and 10 mg/kg) experiment of
      methylphenidate (MPD). Four different locomotor indices were recorded for 2 hours
      postinjection using a computerized monitoring system. Acutely, the 0.6 mg/kg dose
      of MPD did not elicit an increase in locomotor activity in either the adolescent
      or in the adult male SHR. The 2.5 and the 10.0 mg/kg doses increased activity in
      the adolescent and the adult rats. Chronically, MPD treatment when comparing
      adolescent and adult gave the following results: the 0.6 mg/kg dose of MPD failed
      to cause sensitization in the adolescent group but caused sensitization in the
      adult group, while the 2.5 and 10 mg/kg both caused sensitization in the
      adolescent and adult groups.

PMID- 19116831
TI  - Sex differences on components of mental rotation at different menstrual phases.
AB  - Male (n=18) and female (n=16) subjects completed a three-dimensional mental
      rotation task (MRT). The hormonal and MRT data were collected from female
      subjects at low (menstruation) and high (ovulation) estrogen phases. Each
      subject's reaction time (RT) and error rate (ER) were plotted to give the slope
      and intercept of the functions, relating performance to angular disparity. Males
      showed faster RT and lower ER compared to females at each menstrual phase; the
      difference arises from the slope. These findings suggest that there is a sex
      difference in mental rotation at each menstrual phase.

PMID- 19116832
TI  - Red light facilitates the sensed presence elicited by application of weak, burst
      firing magnetic fields over the temporal lobes.
AB  - To test the hypothesis that the wavelength (color) of ambient lightning should
      modulate experiences of a sensed presence when the right hemisphere was
      stimulated by weak, burst-firing magnetic fields, volunteers were exposed for 30
      min to this condition or to a sham field while they sat (eyes opened) in either
      dim red, green, or white light. Subjects exposed to the magnetic field reported
      significantly more visual sensations along the left side in red light and along
      the right side in green light. The significant interaction between ambient color
      and the field treatment was due to the marked increase in experiences of
      dizziness, sensed presence, "ego-alien" thoughts, and detachment from the body
      and "being somewhere else" for subjects exposed to the magnetic field while
      sitting in red light. The concurrence of entoptic images experienced within the
      upper left peripheral visual field and the sensed presence supported the
      hypothesis that both are associated with the intrusion of right hemispheric
      processes into left hemispheric awareness.

PMID- 19116834
TI  - Are masking abnormalities in schizophrenia limited to backward masking?
AB  - Schizophrenia, it has been proposed, is associated with deficits in the
      magnocellular part of the visual system. In support of this suggestion, it has
      been claimed that schizophrenic subjects have abnormal backward masking. However,
      if this abnormality is to be linked specifically to magnocellular defects, then
      it must be specific to backward masking, and not, also effect, for example,
      forward masking. We examined this issue by reviewing the studies of masking in
      schizophrenic subjects. We find: (i) Most studies (56 out of 67) of backward
      masking have researched only backward masking. This makes it impossible to
      determine if the abnormalities found in these studies are exclusively confined to
      backward masking. (ii) Of those studies (11) that have included both forward and
      backward masking conditions, the majority found some degree of abnormality under
      both forward and backward masking conditions. It is concluded that the evidence
      for linking the abnormalities found in those with schizophrenia specifically to
      backward masking, rather than masking in general, or more general visual
      impairments, is at present relatively weak. Given the rationale for using
      backward masking as a test of magnocellular sensitivity, research in this area
      does not point to a deficit specific to the magnocellular system.

PMID- 19116833
TI  - Neural correlates of winning and losing while watching soccer matches.
AB  - The purpose of this study was to examine the emotions experienced by spectators
      when their favorite team wins or loses a soccer match using fMRI. Those who
      watched winning scenes showed activation of the right and left occipital lobes,
      left temporal lobe, left limbic lobe, middle occipital gyrus, superior temporal
      gyrus, cuneus, and uncus. Those who watched losing scenes showed activation of
      the right frontal lobe and right limbic lobe. This result suggests that emotional
      suppression is much stronger in negative emotional responses than in positive
      responses.

PMID- 19116835
TI  - Thought disorder and executive dysfunction in patients with schizophrenia.
AB  - Although, impairment of executive functioning is often reported in schizophrenia,
      its association with thought disorder has not been fully determined. The present
      study examined the relationships between positive thought disorder assessed using
      the Harrow's Thought Disorder Scale (Harrow's scale) and executive function by
      Wisconsin Card Sorting Test (WCST) in 27 inpatients with schizophrenia. Age at
      onset exhibited a significant negative correlation with Wechsler Adult
      Intelligence Scale comprehension test score of Harrow's scale and a significant
      positive correlation with percentage of perseverative errors on the WCST. No
      significant correlations were found between parameters of positive thought
      disorder and executive function. Thought disorder and executive function may play
      different roles in the pathophysiology of schizophrenia.

PMID- 19116836
TI  - Executive functioning and the two-factor model of psychopathy: no differential
      relation?
AB  - There are indications that the interpersonal affective factor and the social
      deviation factor, both of which are underlying dimensions of psychopathy, have a
      positive and a negative relationship, respectively, with executive functioning.
      However, this is seldom taken into consideration in the research on the
      relationship between executive functioning and psychopathy, which may be an
      explanation for the many inconsistent results in this area as reported in the
      literature (e.g., Rogers, 2006). In the present study, executive functioning was
      studied using the Wisconsin Card Sorting Test (WCST) in 53 inpatients of a Dutch
      forensic psychiatric clinic who were classified by means of the Psychopathy
      Checklist-Revised (PCL-R). Special attention was given to the relationship
      between the two separate factors and executive functioning. Age, educational
      level, and substance abuse were controlled for in the analysis. No difference was
      found between psychopathic (N=17) and nonpsychopathic (N=36) patients in the WCST
      scoring categories, nor was there a significant difference in the four diagnostic
      subgroups defined by the two factors. However, the trends observed do justify
      further study in this direction.

PMID- 19116837
TI  - X-ray exposure induces apoptosis of some proliferative epidermal cells following
      traumatic spinal cord injury in adult rats.
AB  - We investigated whether X-ray radiation induced apoptosis of the proliferative
      ependymal cells (ECs) in adult rats with spinal cord injury (SCI) and the effect
      of X-ray radiation on the proliferative activities of ECs. A rat model with SCI
      was developed and used to determine the proliferation and apoptosis of ECs in the
      spinal cords after X-ray exposure. TUNEL assay and BrdU incorporation were used
      to detect apoptosis and proliferation respectively. We found that there were few
      TUNEL-positive cells in proliferative ependymal zone (EZ) after SCI except at the
      epicenter, and approximately half of the irradiated ECs became TUNEL-positive.
      However, these radiated ECs did not lose their proliferative activity until 1
      week later and started to decrease rapidly after 1 week. The observation
      suggested that only part of ECs were sensitive to radiation and the nonsensitive
      cells continued their mitosis process. These findings indicated that X-ray
      exposure of the rats with SCI in early stage induced apoptosis of the
      proliferative ECs and partially inhibited their proliferative activities.

PMID- 19116838
TI  - Association between symptom duration and cerebrospinal fluid pressure, protein
      concentration, and number of cells in patients with intracranial hypotension.
AB  - We sought to investigate the association between symptom duration and
      cerebrospinal fluid (CSF) pressure, protein concentration, and cell counts in
      patients with intracranial hypotension, in addition to examining differences
      between spontaneous and post-traumatic types. We investigated 115 consecutive
      patients with CSF leaks, demonstrated by radionuclide cisternography. In patients
      with spontaneous CSF leaks, a significant decrease in pressure and increase in
      protein concentration and number of cells were observed in patients with a
      symptom duration of <or=3 months compared to those with >3 months. Symptom
      duration was not associated with those CSF parameters in patients with post
      traumatic CSF leaks.

PMID- 19116839
TI  - The effects of stressful life events on the course of multiple sclerosis: a
      review.
AB  - There is growing body of evidence that support an association between stressful
      life events and an increased risk for Multiple Sclerosis (MS) exacerbations.
      However, the nature of this relationship remains unclear, because of the lack of
      agreement about the definition of stress and/or because of research design
      problems. This article summarizes the psychological and biological mechanisms by
      which stress may impact MS progression. Findings indicate a number of factors,
      including stressor chronicity, frequency, severity and type, depression, anxiety,
      health locus of control, optimism, perceived social support, and coping
      strategies. Applied implications are discussed, concentrating on the need for
      multidisciplinary care interventions that target patients' disease symptoms.

PMID- 19116840
TI  - The effect of C-reactive protein on functional outcome in ischemic stroke
      patients.
AB  - This study was performed to evaluate the effect of C-reactive protein (CRP)
      measured within 24 hr after stroke onset on functional outcome in ischemic stroke
      patients. The medical records of 28 first-ever hemiplegic ischemic stroke
      patients with the lesions on the middle cerebral arterial territory were
      reviewed. Subjects were classified into experimental group (serum CRP >or= 0.5
      mg/dL) and control group (serum CRP<0.5 mg/dL) based on the level of serum CRP
      measured within 24 hr after stroke onset. Serum CRP measured within 24 hr after
      stroke onset was significantly correlated with functional scales in ischemic
      stroke patients.

PMID- 19116841
TI  - Intersession reliability of H:M ratio is greater than the H-reflex at a
      percentage of M-max.
AB  - The purpose of this study was to evaluate the intersession reliability of the
      soleus Hoffmann reflex using two methods of normalizing motoneuron excitability
      over time. Ten subjects reported to the laboratory on two separate occasions.
      Soleus Hoffmann reflexes and muscle responses were evaluated at maximal amplitude
      ratios and at stimuli producing approximately 20% of the maximal muscle response.
      An intraclass correlation coefficient (ICC 2, 1) found strong intersession
      reliability for both measurement techniques. Assessing motoneuron activation
      using maximal amplitude ratios demonstrated a robust ICC of 0.979 compared to an
      ICC of 0.882 when the Hoffmann reflex was assessed at approximately 20% of the
      maximal muscle response.

PMID- 19116842
TI  - Testing the distinctiveness of visual imagery and motor imagery in a reach
      paradigm.
AB  - We examined the distinctiveness of motor imagery (MI) and visual imagery (VI) in
      the context of perceived reachability. The aim was to explore the notion that the
      two visual modes have distinctive processing properties tied to the two-visual
      system hypothesis. The experiment included an interference tactic whereby
      participants completed two tasks at the same time: a visual or motor-interference
      task combined with a MI or VI-reaching task. We expected increased error would
      occur when the imaged task and the interference task were matched (e.g., MI with
      the motor task), suggesting an association based on the assumption that the two
      tasks were in competition for space on the same processing pathway.
      Alternatively, if there were no differences, dissociation could be inferred.
      Significant increases in the number of errors were found when the modalities for
      the imaged (both MI and VI) task and the interference task were matched.
      Therefore, it appears that MI and VI in the context of perceived reachability
      recruit different processing mechanisms.

PMID- 19116843
TI  - Can subdural hematoma be a trigger for Guillain-Barre syndrome?
AB  - Guillain-Barre syndrome (GBS) is an acute inflammatory polyneuropathy which
      follows a precipitating event in approximately two thirds of cases. Although its
      pathogenesis is unclear, it is likely to be a consequence of an immune-mediated
      process. In the literature there are three case reports of GBS following
      subarachnoid hemorrhage, subdural hematoma, and facial bone fracture after head
      trauma.The unique feature of our case with GBS after subdural hematoma is the
      presence of cerebellar symptoms. We believe that GBS results from an aberrant
      immune response following trauma that somehow mistakenly attacks the nerve tissue
      of its host, and we discuss the effects of the trauma of head injury on cellular
      and humoral immunities and the absence of antiganglioside antibody (anti-GD1b
      IgG, which is accused of ataxia and cerebellar symptoms) in this case report.

PMID- 19116844
TI  - Temporal dissociation of global and local features by hierarchy of vision.
AB  - Most objects in our environment are organized hierarchically with a global whole
      embedding its local parts, but the way we recognize these features remains
      unclear. Using a visual masking paradigm, we examined the temporal dissociation
      between global and local feature as proposed in Reverse Hierarchy Theory, RHT
      (Ahissar & Hochstein, 2000), where global and local information are assumed to be
      processed, respectively, by feed-forward and feedback systems. We found that in a
      long Stimulus Onset Asynchrony (SOA) condition, both global and local information
      were recognized adequately. However, in a short SOA condition, global information
      was recognized correctly while local recognition was critically disrupted.
      Consistent with RHT, it is suggested that local information is processed in a
      feedback system; this processing is then interrupted by the mask stimulus
      presented later at the primary visual area. Global information, by contrast, is
      transferred via a feed-forward system, and is not disrupted by the mask.

PMID- 19116845
TI  - Long-term astroglial reaction and neuronal plasticity in the subcortical visual
      pathways after a complete ablation of telencephalon in pigeons (Columba livia).
AB  - This paper analyzes the astroglial and neuronal responses in subtelencephalic
      structures, following a bilateral ablation of the telencephalon in the Columba
      livia pigeons. Control birds received a sham operation. Four months later the
      birds were sacrificed and their brains processed for glial fibrillary acid
      protein (GFAP) and neurofilament immunohistochemistry, markers for astrocytes and
      neurons, respectively. Computer-assisted image analysis was employed for
      quantification of the immunoreactive labeling in the nucleus rotundus (N.Rt) and
      the optic tectum (OT) of the birds. An increased number of GFAP immunoreactive
      astrocytes were found in several subregions of the N.Rt (p< .001), as well as in
      layers 1, 2cd, 3, and 6 of the OT (p< .001) of the lesioned animals.
      Neurofilament immunoreactivity decreased massively in the entire N.Rt of the
      lesioned birds; however, remaining neurons with healthy aspect showing large
      cytoplasm and ramified branches were detected mainly in the periphery of the
      nucleus. In view of the recently described paracrine neurotrophic properties of
      the activated astrocytes, the data of the present study may suggest a long
      lasting neuroglial interaction in regions of the lesioned bird brain far from
      injury. Such events may trigger neuronal plasticity in remaining brain structures
      that may lead spontaneous behavior recovery as the one promoted here even after a
      massive injury.

PMID- 19116846
TI  - Differentiating a network of executive attention: LORETA neurofeedback in
      anterior cingulate and dorsolateral prefrontal cortices.
AB  - INTRODUCTION: This study examines the differential effects of space-specific
      neuro-operant learning, utilizing low-resolution electromagnetic tomographic
      (LORETA) neurofeedback in three regions of training (ROTs), namely, the anterior
      cingulate gyrus (AC) and right and left dorsolateral prefrontal cortices (RPFC
      and LPFC respectively). METHODS: This study was conducted with 14 nonclinical
      students with a mean age of 22. We utilized electrophysiological measurements and
      subtests of the WAIS-III for premeasures and postmeasures. RESULTS: The data
      indicate that the AC shares a significant association with the RPFC and LPFC;
      however, each of the ROTs exhibits different cortical effects in all frequencies
      when trained exclusively. DISCUSSION: LORETA neurofeedback (LNFB) appears to
      enhance the functioning and strengthening of networks of cortical units
      physiologically related to each ROT; moreover, significant changes are mapped for
      each frequency domain, showing the associations within this possible attentional
      network.

PMID- 19116847
TI  - Temporal facilitation prior to voluntary muscle relaxation.
AB  - We investigated the dominancy of excitability changes in motor cortex or spinal
      levels and temporal tuning mechanisms of muscle relaxation. We delivered
      transcranial magnetic stimulation and electric (H-reflex) stimulations relative
      to the application of the response signal under the reaction time task. The
      results showed that a significant change was found in only motor evoked potential
      during the prerelaxation phase, 30 ms after the response signal presented for
      muscle relaxation, but similar changes were not found in H-reflex. We suggested
      that this phenomenon, may be, reflects on excitation of corticospinal neurons,
      which consequently play an important role for muscle relaxation.

PMID- 19116848
TI  - ECG signal compression using combined modified discrete cosine and discrete
      wavelet transforms.
AB  - A new hybrid two-stage electrocardiogram (ECG) signal compression method based on
      the modified discrete cosine transform (MDCT) and discrete wavelet transform
      (DWT) is proposed. The ECG signal is partitioned into blocks and the MDCT is
      applied to each block to decorrelate the spectral information. Then, the DWT is
      applied to the resulting MDCT coefficients. Removing spectral redundancy is
      achieved by compressing the subordinate components more than the dominant
      components. The resulting wavelet coefficients are then thresholded and
      compressed using energy packing and binary-significant map coding technique for
      storage space saving. Experiments on ECG records from the MIT-BIH database are
      performed with various combinations of MDCT and wavelet filters at different
      transformation levels, and quantization intervals. The decompressed signals are
      evaluated using percentage rms error (PRD) and zero-mean rms error (PRD(1))
      measures. The results showed that the proposed method provides low bit-rate and
      high quality of the reconstructed signal. It offers average compression ratio
      (CR) of 21.5 and PRD of 5.89%, which would be suitable for most monitoring and
      diagnoses applications. Simulation results show that the proposed method compares
      favourably with various state-of-the-art ECG compressors.

PMID- 19116849
TI  - Computer-assisted femoral head resurfacing.
AB  - Femoral head resurfacing (FHR) is an alternative to total hip replacement (THR)
      and is particularly suitable for the younger, more active patients. However, this
      procedure is more difficult than THR, the mechanical jigs routinely used to align
      the implant produce significant variability in implant placement, and proper
      positioning process is time-consuming. This paper is concerned with the
      construction of mathematical model of femoral head and neck and a computer
      assisted femoral head resurfacing system. On the basis of numerical optimization
      theory, a series of mathematical equations are derived to describe the femoral
      head and neck. By adopting techniques and tools such as optical tracking,
      numerical analysis, and computer graphics, a 3D digital model of femoral head and
      neck is reconstructed, and a FHR system is developed. With the aid of this
      software, visualization and pin placement can be easily achieved. Experimental
      results in this study show that the FHR system provides a useful tool for
      performing the femoral head resurfacing surgery quickly and accurately.

PMID- 19116850
TI  - An image analysis method for prostate tissue classification: preliminary
      validation with resonance sensor data.
AB  - Resonance sensor systems have been shown to be able to distinguish between
      cancerous and normal prostate tissue, in vitro. The aim of this study was to
      improve the accuracy of the tissue determination, to simplify the tissue
      classification process with computerized morphometrical analysis, to decrease the
      risk of human errors, and to reduce the processing time. In this article we
      present our newly developed computerized classification method based on image
      analysis. In relation to earlier resonance sensor studies we increased the number
      of normal prostate tissue classes into stroma, epithelial tissue, lumen and
      stones. The linearity between the impression depth and tissue classes was
      calculated using multiple linear regression (R(2) = 0.68, n = 109, p < 0.001) and
      partial least squares (R(2) = 0.55, n = 109, p < 0.001). Thus it can be concluded
      that there existed a linear relationship between the impression depth and the
      tissue classes. The new image analysis method was easy to handle and decreased
      the classification time by 80%.

PMID- 19116851
TI  - Study on a miniature robotic system for active monitoring in the human
      respiratory tract.
AB  - A three degrees-of-freedom inchworm-type robot is presented for miniature
      endoscope inspection in the human respiratory system. The robot is actuated with
      pneumatic artificial muscle and clamped by two air chambers. The robot's extra
      resistance in the human trachea is analysed in detail and the dynamic model of
      the robot is built. In order to solve the problems of low stiffness and the
      nonlinear movement characteristic of the pneumatic robotic system, a fuzzy
      wavelet neural network controller is proposed to control the robot position servo
      system using the principle of pulse width modulation. Simulation and experimental
      results both demonstrate that the training of the fuzzy wavelet neural network
      controller is faster and the control quality is effectively improved. The
      monitoring experiments had been done in a swine trachea during mechanical
      ventilation, and the miniature system can dynamically measure respiratory
      parameters.

PMID- 19116852
TI  - Real-life step and activity measurement: reliability and validity.
AB  - OBJECTIVES: Investigation of the reliability and validity of activity monitoring
      using a range of methods, namely manual counting, self report and two
      commercially available activity monitors. STUDY DESIGN: Reliability, accuracy and
      validity study. METHODS: Multiple convenience samples of healthy subjects were
      recruited to the study. Reliability of manual step count was determined using an
      intraclass correlation coefficient (ICC) (n = 10). Relationships between data
      from the Step Watch monitor (SAM) and (a) manual step counts (n = 18); (b) a
      second (different) activity monitor (ActivPAL); and (c) self reported activity
      levels (n = 22) were assessed using correlations. A Pearson's correlation and
      paired t-test was used to assess relations between routinely used monitors.
      RESULTS: Intra-rater reliability for manual step counts was excellent (ICC 0.99),
      but inter-rater reliability was poor (ICC 0.26). Indoor accuracy of the SAM was
      96.06% and outdoor accuracy was 99.58%. Moderate correlations (rho = 0.423 to
      0.595, p < 0.05) were identified between the SAM monitor activity levels and self
      report diaries. The SAM and the ActivPAL were found to be internally reliable
      within themselves (ICC 0.96 and 0.95 respectively), significantly correlated (r =
      0.93, p < 0.001) but also significantly different (t = 2.179, p < 0.05) when used
      simultaneously over the same circuit. CONCLUSIONS: Activity monitors provide
      information that is related to actual activity and provide accurate and reliable
      data when tested on functional walking circuits. Activity monitors should not be
      used interchangeably due to the potential for systematic differences between the
      measurements obtained when applied simultaneously over the same repeated circuit.

PMID- 19116853
TI  - Analysis of epileptic EEG signals using higher order spectra.
AB  - The unpredictability of the occurrence of epileptic seizures contributes to the
      burden of the disease to a major degree. An automatic system that detects seizure
      onsets would allow patients or the people near them to take appropriate
      precautions, and could provide more insight into these phenomena, thereby
      revealing important clinical information. Thus, various methods have been
      proposed to predict the onset of seizures based on EEG recordings. A seemingly
      promising approach involves nonlinear features motivated by the higher order
      spectra (HOS). The goal in this paper is to find the different HOS features for
      normal, pre-ictal (background) and epileptic EEG signals. This may help in the
      detection of seizure onset as early as possible with maximal accuracy. In this
      work, 300 EEG data, each belonging to the three classes, are studied. Our results
      show that the HOS based measures show unique ranges for the different classes
      with high confidence level (p = 0.002).

PMID- 19116854
TI  - The effectiveness of the wavelet transforms method in the heart sounds analysis.
AB  - Heart sounds can be used more efficiently by medical doctors when they are
      displayed visually, rather through a conventional stethoscope. Heart sounds
      provide clinicians with valuable diagnostic and prognostic information. Although
      heart sound analysis by auscultation is convenient as a clinical tool, heart
      sound signals are so complex and non-stationary that they are very difficult to
      analyse in time or frequency domains. We have studied the extraction of features
      from heart sounds in the time-frequency domain for recognition of heart sounds
      through time-frequency analysis. The application of wavelet transform for the
      heart sounds is thus described. The performance of continuous wavelet transform,
      discrete wavelet transform and packet wavelet transform is discussed in this
      paper. After these transformations, we can compare normal and abnormal heart
      sounds to verify clinical usefulness of our extraction methods for recognition of
      heart sounds.

PMID- 19116855
TI  - Multi-sensor radiotelemetry system for intestinal motility measurement.
AB  - In order to measure the important physiological parameters such as temperature,
      pressure and pH value, we developed a miniature, high precision, non-invasive and
      multi-sensor radiotelemetry system. The system comprises multi-sensor
      radiotelemetry capsule, data logger, location device and workstation. The
      radiotelemetry capsule can monitor the pH, pressure and temperature of the entire
      intestinal tract and send the data to the data logger outside the body through a
      wireless communication link. After the capsule is egested from the anus, further
      analysis of the physiological parameter data saved in the data logger can be
      performed via the special software installed at the workstation. Clinical
      experiments prove that the radiotelemetry system is non-invasive and reliable.
      Moreover it is found that the radiotelemetry system is an effective method to
      study intestine motility characteristics.

PMID- 19116856
TI  - A new tool for the management of infection in patients with febrile neutropenia.
AB  - BACKGROUND: We describe a novel analytical technique for determining
      instantaneous trends in body temperature data, which may assist clinicians in
      optimizing antimicrobial therapy in patients with febrile neutropenia. The paper
      presents a new algorithm, based on a modified second backward difference (M2BD)
      matrix filter for monitoring temperature response to anti-microbial
      chemotherapies in neutropenic patients and develops techniques for extracting
      accurate, instantaneous trend data from clinical time series data. Such an
      algorithm is needed because it is difficult to assess patient wellbeing in those
      who are neutropenic. Temperature data, a key indicator of response to
      antimicrobial therapy, are typically very noisy, with many fluctuations, making
      it very difficult to identify underlying trends in real time. Clinicians are
      therefore forced to make important decisions concerning drug therapy on imperfect
      data. METHODS: In order to determine the underlying temperature trend, analysis
      of synthetic time series data (with a known underlying trend) was undertaken
      using both the CUSUM technique and the M2BD matrix filter. The CUSUM analysis was
      undertaken using four reference temperatures, 37.5 degrees C, 38.0 degrees C,
      38.5 degrees C and 39.0 degrees C. A validation study was also undertaken using
      four sets of noisy synthetic temperature data to evaluate the performance of the
      M2BD filter. The M2BD filter was then used to analyse anonymized serial
      temperature data from a neutropenic patient undergoing chemotherapy. RESULTS: For
      all four reference temperatures the CUSUM analysis failed to predict the
      underlying temperature trend. By comparison, the M2BD filter extracted, in real
      time, the underlying temperature trend with great accuracy and no time lag. In
      the validation study, the M2BD filter accurately extracted the underlying
      temperature trend for all four of the synthetic datasets. With regard to the
      anonymized patient data, the M2BD filter again performed well, accurately
      determining the underlying trend. CONCLUSION: The study demonstrated that the
      M2BD filter is capable of instantaneously extracting underlying trends from
      clinical time series data. This finding suggests that this algorithm has great
      potential as a tool for assisting clinicians in the management of patients with
      febrile neutropenia.

PMID- 19116857
TI  - Clinical applications of pulse transit time in paediatric critical care.
AB  - A simple and non-invasive technique, termed pulse transit time (PTT), has shown
      its potential in long-term investigations such as respiratory sleep studies and
      cardiovascular studies. Based on these findings, the PTT technique shows
      relevance for continuous haemodynamic monitoring in critical care. The objective
      of this review is to understand the potential, applications and limitations of
      PTT in this clinical setting. Present non-invasive haemodynamic monitoring
      methods such as automated oscillometric blood pressure (BP) and auscultatory
      techniques have their known limitations. They tend to underestimate systolic BP
      while overestimating diastolic BP. Due to the periodic increase in cuff pressure
      cycles during data acquisition, these techniques may cause much discomfort in
      elderly geriatric patients, or lessen the cooperation of younger paediatric
      patients. Thus, there can be adverse effects on therapeutic decisions and
      possibly clinical outcomes. Documented evidences have indicated that changes
      observed in PTT are inversely correlated to the corresponding BP changes. In
      critical care, a simple and accommodating technique like PTT may be useful in
      providing better comfort for patients during extended monitoring. Being a semi
      quantitative measure, blanket recommendations for its utility can then become
      possible. The basic instrumentations needed are often part of standard critical
      care monitoring system. Furthermore, PTT also has the potential to monitor the
      often tachypnoeic respiratory dependent BP changes seen in small infants during
      critical care.

PMID- 19116858
TI  - Design and development of anthropometric device for the standardization of sizes
      of knee-ankle-foot orthoses.
AB  - An anthropometric device (AD) was designed and developed to collect data on foot
      and knee of locomotor disabled people. The aim was to standardize the sizes of
      knee-ankle-foot orthoses (KAFOs) in a standard modular form so that they can be
      mass produced to cater for fitting to a large number of locomotor disabled
      people. The anthropometric data collected on large numbers of locomotor disabled
      people were processed, with the help of a computer programme, to arrive at
      standard sizes for three modules, i.e. a foot plate (seven sizes), knee pieces
      (six sizes) and a lateral upright in a universal size. These modules were
      produced by plastic injection moulding and compression moulding processes using
      glass-reinforced polypropylene. KAFOs were assembled and fitted to locomotor
      disabled people. Feedback obtained was encouraging and this vindicated the
      concept, design and utility of the AD.

PMID- 19116861
TI  - Applications and findings of an occupational exposure database for synthetic
      vitreous fibers.
AB  - Occupational exposure databases are being used increasingly to characterize
      worker exposures in industries involving a variety of exposure scenarios. The
      glass and rock/slag segments of the synthetic vitreous fiber industry (in the
      United States) has developed a large (>14,000 samples) exposure database that can
      be used to estimate worker exposures based on industry sector, fiber type,
      product type, and job function. This article describes the development of this
      database as part of an industry-Occupational Safety and Health Administration
      collaborative Health and Safety Partnership Program and summarizes the findings
      and potential applications of the database.

PMID- 19116862
TI  - Residual methamphetamine in decontaminated clandestine drug laboratories.
AB  - This pilot cross-sectional study examined three previously decontaminated
      residential clandestine drug laboratories (CDLs) in Washington State to determine
      the distribution and magnitude of residual methamphetamine concentrations
      relative to the state decontamination standard. A total of 159 discrete random
      methamphetamine wipe samples were collected from the three CDLs, focusing on the
      master bedroom, bathroom, living room, and kitchen at each site. Additional
      samples were collected from specific non-random locations likely to be contacted
      by future residents (e.g., door knobs and light switches). Samples were analyzed
      for methamphetamine by EPA method 8270 for semivolatile organic chemicals.
      Overall, 59% of random samples and 75% of contact point samples contained
      methamphetamine in excess of the state decontamination standard (0.1 micro g/100
      cm(2)). At each site, methamphetamine concentrations were generally higher and
      more variable in rooms where methamphetamine was prepared and used. Even compared
      with the less stringent standard adopted in Colorado (0.5 micro g/100cm(2)), a
      substantial number of samples at each site still demonstrated excessive residual
      methamphetamine (random samples, 25%; contact samples, 44%). Independent
      oversight of CDL decontamination in residential structures is warranted to
      protect public health. Further research on the efficacy of CDL decontamination
      procedures and subsequent verification of methods is needed.

PMID- 19116863
TI  - Sexual desire, communication, satisfaction, and preferences of men and women in
      same-sex versus mixed-sex relationships.
AB  - In an online study, measures of subjective sexual experiences in one's current
      relationship were compared across four groups: Men and women in mixed-sex (i.e.,
      heterosexual) and same-sex (i.e., homosexual) relationships. Results indicated
      far more similarities than differences across the four groups, with groups
      reporting almost identical sexual repertoires, and levels of sexual communcation
      with partner. Men reported experiencing somewhat more sexual desire than women,
      while women reported slightly higher levels of general sexual satisfaction than
      men. Those in same-sex relationships reported slightly higher levels of sexual
      desire than those in mixed-sex relationships. Compared to the other three groups,
      heterosexual men reported deriving somewhat less satisfaction from the more
      tender, sensual, or erotic sexual activities. Implications of these findings for
      sex therapists are discussed.

PMID- 19116864
TI  - Early sexual behavior in a sample of low-income, African American Children.
AB  - This study describes the sexual behavior of 2- to 12-year-old African American
      children without known histories of sexual abuse and explores the relation of
      this behavior to gender and age. Primary caregivers were recruited from a public
      "Well Child" clinic and administered the Child Sexual Behavior Inventory (CSBI),
      a parental report measure that assesses a broad range of childhood sexual
      behaviors within 9 specific domains. CSBI data were collected on 249 African
      American children. Results indicate that African American children display a
      broad range of sexual behavior that was not reported to frequently occur. Sexual
      behaviors that involved requesting, planning, or forcing other children and
      adults into sexual activity were not reported. Although significant differences
      were not found between frequency levels of sexual behavior reported for boys and
      girls, the range of sexual behavior observed and reported for girls was narrower
      in comparison to boys. Significant differences were found between frequency
      levels of sexual behavior observed and reported for children of different ages.
      Analysis of the behavioral differences found between children of different ages
      indicates the emergence of a marked interest in sexuality as African American
      children approached puberty.

PMID- 19116865
TI  - Big beautiful women: the body size preferences of male fat admirers.
AB  - This study examined the body size ideals of a group of male fat admirers (FAs) in
      comparison with an age- and body mass index (BMI)-matched control sample. Forty
      seven men, who were involved in the fat acceptance community, and 64 control
      individuals rated a series of 10 images of women that varied in BMI from
      emaciated to obese. As expected, the results showed that FAs rated a
      significantly higher BMI as the most physically attractive compared with the
      control sample. FAs also rated figures with higher BMIs, particularly those in
      overweight and obese categories, more positively than did the control group. In
      addition, FAs perceived a wider range of body sizes to be physically attractive
      than the control group. Participant demographics did not predict ratings over and
      above affiliation with either the FA or control groups. These results are
      discussed in relation to the growing body of work examining fat admiration.

PMID- 19116866
TI  - Downregulation of human telomerase reverse transcriptase through anti-C-myc siRNA
      in human colon cancer Colo 320 cells.
AB  - The c-Myc and human telomerase reverse transcriptase gene (hTERT) gene are
      frequently deregulated and overexpressed in malignancy. hTERT activity is induced
      by c-Myc and strategies designed to inhibit c-Myc expression in cancer cells may
      have considerable therapeutic value. We designed and used a short hairpin RNA to
      inhibit c-Myc expression in Colo 320 cells and validated its effect on cell
      proliferation. In this study, four c-Myc-shRNA expression vectors were
      constructed and introduced into Colo 320 cells. The effects of c-Myc silencing on
      tumor cell growth was assessed by soft agar assay and DNA synthesis and MTT
      experiments. The expressions of c-Myc and hTERT were also assessed by real-time
      reverse transcription-polymerase chain reaction and Western blot analysis. Upon
      transient transfection with plasmid encoding shRNA, it was found that expression
      of c-Myc and hTERT decreased in shRNA-transfected cells. The downregulation of c
      Myc and hTERT inhibited cell growth, shortened telomere lengths, and suppressed
      telomerase activity. In conclusion, our findings demonstrate that shRNA of c-Myc
      can inhibit the DNA replication in Colo 320 cells effectively and reduce telomere
      length and telomerase activity; therefore, it could be used as a new potential
      anticancer tool for therapy of human colon cancer.

PMID- 19116867
TI  - Visible-light photocontrol of (E)/(Z) isomerization of the 4
      (dimethylamino)azobenzene pseudo-nucleotide unit incorporated into an
      oligonucleotide and DNA hybridization in aqueous media.
AB  - We demonstrate significant photoresponsivity in aqueous media to visible light of
      pseudo-oligonucleotides possessing 4-(dimethylamino)azobenzene (4-DMAzo) side
      chains. The spectrum of the 4-DMAzo moiety during 436 nm light irradiation at pH
      >9 was clearly different from that of the all (E)-form, indicating the presence
      of the (Z)-form. Thermal (Z)-to-(E) recovery isomerization was faster at pH 9
      (k(Z)(-E) = approximately 10(1) s(-1)) than at pH 11; however, addition of 50%
      ethanol significantly slowed the thermal recovery isomerization at pH 9 (k(Z)(-E)
      = approximately 2 s(-1)) and increased the magnitude of the spectral changes.
      Significant photoregulation of DNA hybridization by visible light was
      demonstrated under this condition.

PMID- 19116868
TI  - A proposal for a convenient notation for P-chiral nucleotide analogues. Part 4. A
      relationship between the Dp/Lp notation and stereochemistry of reactions.
AB  - Recently, we have proposed a new D(P)/L(P) stereochemical notation for P-chiral
      dinucleoside monophosphate analogues based on a structural relationship between
      compounds. As an extension of this work, we present here applications of the
      D(P)/L(P) notation for tracking stereochemistry of reaction pathways involving H
      phosphonate, phosphoramidite, phosphorotriester, and other intermediates
      frequently met in the nucleotide chemistry.

PMID- 19116869
TI  - 5'-O-D-valyl ara A, a potential prodrug for improving oral bioavailability of the
      antiviral agent vidarabine.
AB  - In order to improve the oral bioavailability of Adenine 9-beta-D
      arabinofuranoside (Vidarabine, also called ara A), an antiviral drug which is
      active against herpes simplex and varicella zoster viruses and the first agent to
      be licensed for the treatment of systematic herpes virus infection in man, the
      corresponding 5'-O-D-valyl ester derivative has been synthesized. Based on their
      physicochemical properties, 5'-O-valyl ara A has emerged as a potential prodrug
      candidate to improve the oral bioavailability of vidarabine. We describe in this
      paper a facile synthesis route for the prodrug and its physicochemical
      properties.

PMID- 19116870
TI  - Facile synthesis and anti-tumor cell activity of Se-containing nucleosides.
AB  - Many organic compounds containing selenium have shown anticancer effects and some
      have been used in chemoprevention of cancers and other diseases. Though Se
      containing amino acids are generally used for these purposes, the natural
      nucleosides may also be used as Se-carriers for these important applications.
      Therefore, we describe here the convenient synthesis of the new 3'-MeSe-thymidine
      nucleoside and the other uridine and thymidine derivatives modified with MeSe at
      the 2' and 5' positions, and report their anti-tumor activity against prostate
      cancer cell lines. Our work demonstrates for the first time anticancer activity
      of the methylseleno nucleosides.

PMID- 19116872
TI  - Pharmacological values of medicinal mushrooms for prostate cancer therapy: the
      case of Ganoderma lucidum.
AB  - Prostate cancer (PCa) is the most common male malignancy in many Western
      countries. Primary PCa is hormone dependent and is manageable by hormonal
      therapy. However, it rapidly develops to hormone-refractory tumors due to the
      accumulation of mutations in the androgen receptor and/or the acquisition of
      alternative cellular pathways that support proliferation and inhibit apoptosis of
      prostate cancer. To date, no effective therapy is available for clinically
      hormone-insensitive or hormone-refractory stages of prostate cancer.

PMID- 19116871
TI  - Alcohol consumption and the risk of nasopharyngeal carcinoma: a systematic
      review.
AB  - The evidence concerning the influence of alcohol drinking on the risk of
      nasopharyngeal carcinoma (NPC) has yielded intriguing findings but has lacked a
      clear-cut interpretation due to inconsistencies. To unify this body of evidence,
      we performed a systematic review. With funding and using a protocol developed by
      the World Cancer Research Fund (WCRF), 15 bibliographic databases were searched
      for epidemiological studies that reported a measure of association between
      alcoholic beverage consumption and NPC. Pooled odds ratios (ORs) for highest-vs.
      lowest categories of total alcohol intake was obtained by using an inverse
      variance weighted random-effects model. A dose-response trend was examined in
      models using generalized least square estimation. The search identified 14 case
      control studies from 5 countries. For total alcohol intake, the pooled ORs in a
      comparison of the highest to the lowest category was 1.33 (95% CI: = 1.09-1.62)
      in 11 studies. Data from 6 studies indicated a J-shape dose-response trend, with
      NPC risk decreasing with up to 15 drinks/wk and increasing with higher intake.
      Fewer data were available to assess the associations between NPC and intake of
      beer, wine, and spirits. The potential J-shaped dose-response trend suggests a
      reduced risk of NPC related to the light alcohol drinking, an observation that
      warrants further study. Considered in total, the quantitative summaries of the
      case-control evidence suggest that heavy alcohol consumption is associated with
      an increased risk of NPC.

PMID- 19116873
TI  - Cancer chemopreventive and therapeutic effects of diosgenin, a food saponin.
AB  - Cancer chemoprevention is a strategy taken to retard, regress, or resist the
      multistep process of carcinogenesis, including the blockage of its vital
      morphogenetic milestones viz. normal-preneoplasia-neoplasia-metastasis. For
      several reasons, including safety, minimal (or no) toxicity and side-effects, and
      better availability, alternatives such as naturally occurring phytochemicals that
      are found in foods are becoming increasingly popular over synthetic drugs. Food
      saponins have been used in complimentary and traditional medicine against a
      variety of diseases including several cancers. Diosgenin, a naturally occurring
      steroid saponin found abundantly in legumes and yams, is a well-known precursor
      of various synthetic steroidal drugs that are extensively used in the
      pharmaceutical industry. Over the past decade, a series of preclinical and
      mechanistic studies have been conducted to understand the role of diosgenin as a
      chemopreventive/therapeutic agent against several cancers. This review highlights
      the biological activity of diosgenin that contributes to cancer chemoprevention
      and control. The anticancer mode of action of diosgenin has been demonstrated via
      modulation of multiple cell signaling events involving critical molecular
      candidates associated with growth, differentiation, apoptosis, and oncogenesis.
      Altogether, these preclinical and mechanistic findings strongly implicate the use
      of diosgenin as a novel, multitarget-based chemopreventive or therapeutic agent
      against several cancer types. Future research in this field will help to
      establish not only whether diosgenin is safe and efficacious as a chemopreventive
      agent against several human cancers, but also to develop and evaluate standards
      of evidence for health claims for diosgenin-containing foods as they become
      increasingly popular and enter the marketplace labeled as functional foods and
      nutraceuticals.

PMID- 19116875
TI  - Colorectal cancer risk and dietary intake of calcium, vitamin D, and dairy
      products: a meta-analysis of 26,335 cases from 60 observational studies.
AB  - In vivo and in vitro studies suggest that dairy products, calcium, and dietary
      vitamin D inhibits the development of colorectal cancer (CRC). A meta-analysis
      was performed to evaluate this relationship in observational studies. Data from
      60 epidemiological studies enrolling 26,335 CRC cases were pooled using a general
      variance-based meta-analytic method. Summary relative risk (RR) estimates and 95%
      confidence intervals (CIs) were calculated for the highest vs. the lowest intake
      categories. Sensitivity analyses tested the robustness of these summary effect
      measures and the statistical heterogeneity. The summary RR for high milk and
      dairy product intake, respectively, on colon cancer risk was 0.78 (95% CI = 0.67
      0.92) and 0.84 (95% CI = 0.75-0.95). Milk intake was unrelated to rectal cancer
      risk. High calcium intake had a greater protective effect against tumors of the
      distal colon and rectal cancer vs. proximal colon. The risk reduction associated
      with calcium was similar for dietary and supplemental sources. Vitamin D was
      associated with a nonsignificant 6% reduction in CRC risk. Higher consumption of
      milk/dairy products reduces the risk of colon cancer, and high calcium intake
      reduces the risk of CRC. Low vitamin D intake in the study populations may limit
      the ability to detect a protective effect if one exists.

PMID- 19116874
TI  - Meat consumption, heterocyclic amines, NAT2, and the risk of breast cancer.
AB  - Meat consumption and heterocyclic amine (HCA) intake have been inconsistently
      associated with breast cancer risk in epidemiologic studies. Genetic variation in
      N-acetyltransferase2 (NAT2) has been suggested to modify the association of meat
      intake with breast cancer through its influence on metabolism of HCAs. We
      examined associations between meat intake, HCA exposure, acetylator genotype, and
      breast cancer risk in a case-control study of 2,686 case women and 3,508
      controls. Women were asked to report their usual intake, cooking method, and
      preferred doneness of specific meats. We observed no association between total
      meat, red meat, or chicken with breast cancer risk. Women who consumed 5 or more
      servings of meat per week had no increased risk of breast cancer compared to
      women consuming fewer than 2 servings per week (OR = 0.99, 95% CI 0.84-1.15). No
      statistically significant associations with breast cancer were found for
      individual HCAs or for total estimated mutagenic activity of meat. Results varied
      modestly according to menopausal status. There were no statistically significant
      interactions with NAT2 genotype. Results do not support an important association
      of HCAs with breast cancer risk, although potential biases in case-control
      studies should be considered.

PMID- 19116876
TI  - Dietary vitamin D intake and cancers of the colon and rectum: a case-control
      study in Italy.
AB  - Epidemiologic evidence indicates that vitamin D is inversely associated with risk
      of colon or rectal cancer or both. Using data from a case-control study conducted
      in Italy between 1992 and 1996, we examined the relation between dietary intake
      of vitamin D and colon and rectal cancer risk. The study population comprised
      patients with incident colon cancer (n = 1,225) or rectal cancer (n = 728) and
      4,154 hospital controls. Odds ratios (OR) and 95% confidence intervals (CI)
      according to deciles of vitamin D intake were estimated by multiple logistic
      regression. In addition, we adjusted for intensity of sunlight exposure through
      stratification by geographic region of residence, and we computed ORs separately
      by anatomic subsite within the colon. Adjusted ORs for colon cancer were seen to
      decrease after the 5th decile of vitamin D intake and reached 0.69 (95% CI = 0.50
      0.96) for the 9th and 10th deciles, reflecting a statistically significant
      inverse trend. The inverse association appeared to be somewhat more pronounced
      for the proximal than the distal colon and was similar among strata of geographic
      region and calcium intake. Rectal cancer was unrelated to vitamin D intake in
      this population. In conclusion, we observed an inverse association between
      dietary vitamin D intake and colon cancer risk among those with the highest
      intake levels, which was somewhat unexpected given that these levels were still
      substantially below the levels considered optimal for colon cancer prevention.

PMID- 19116877
TI  - Coffee, decaffeinated coffee, tea intake, and risk of renal cell cancer.
AB  - The relation between coffee, decaffeinated coffee, and tea intake and renal cell
      carcinoma (RCC) risk was analyzed in a case-control study conducted in Italy
      between 1992 and 2004. Cases were 767 subjects with incident histologically
      confirmed RCC and controls were 1,534 patients in hospital for acute non
      neoplastic conditions. Odds ratios (OR) and 95% confidence intervals (CI) for RCC
      were computed by multiple logistic regression models, conditioned on study
      center, sex, and age. Coffee intake (mostly espresso and mocha) was not
      associated with RCC risk, with an OR of 1.02 (95% CI 0.73-1.43) in drinkers of >
      or = 4 cups/day compared with drinkers of < 1 cup/day. The corresponding ORs were
      1.34 (95% CI 0.87-2.07) in men and 0.67 (95% CI 0.38-1.18) in women, 1.91 (95% CI
      0.85-4.31) in current smokers and 0.74 (95% CI 0.41-1.31) in never smokers, with
      no trend in risk with dose. No relation was observed with decaffeinated coffee
      (OR = 1.38, 95% CI 0.94-2.03 for drinkers compared with nondrinkers) and tea
      intake (OR = 0.78, 95% CI 0.59-1.05 for drinkers of > or = 1 cup/day compared
      with nondrinkers). No significant heterogeneity was found for coffee intake
      across strata of age, education, body mass index, and consumption of sugar. This
      study, based on a large dataset, provides further evidence that coffee,
      decaffeinated coffee, and tea consumption are not related to RCC risk.

PMID- 19116878
TI  - High sucrose diets promote intestinal epithelial cell proliferation and
      tumorigenesis in APC(Min) mice by increasing insulin and IGF-I levels.
AB  - Epidemiological studies report that high sucrose consumption is associated with
      increased risk of colon cancer. One hypothesis is that this association is
      mediated by elevated circulatory insulin and IGF levels promoting intestinal
      proliferation. To test this hypothesis, APC(Min) mice and their wild type
      littermates were fed, starting at 4 wk of age, sucrose or cornstarch as the sole
      carbohydrate source in the absence or presence of low levels of dietary sulindac
      for 10 or 16 wk, respectively. APC(Min) mice fed sucrose had an increased tumor
      number in the proximal third of the small intestine in both studies and a higher
      incidence of papillary colon tumors in the 16-wk feeding study (P < or = 0.05).
      Mice fed sucrose (relative to cornstarch) had higher body weights and greater
      Ki67-labeling indexes in colonic epithelium than mice fed cornstarch in both
      feeding studies (P < or = 0.05). Furthermore, mice fed sucrose had higher serum
      glucose and liver IGF-I mRNA concentrations (P < or = 0.05) and tended to have
      higher serum insulin levels (P = 0.08). These results support the hypothesis that
      high dietary sucrose intake promotes intestinal proliferation and tumorigenesis
      by increasing circulating levels of insulin and IGF-I.

PMID- 19116879
TI  - Carnosol delays chemotherapy-induced DNA fragmentation and morphological changes
      associated with apoptosis in leukemic cells.
AB  - Carnosol, from the herb rosemary, has been shown to induce apoptotic cell death
      in high-risk pre-B acute lymphoblastic leukemia (ALL). In the present study,
      carnosol was tested for its ability to sensitize leukemia cells to
      chemotherapeutic agents. Carnosol reduced the percentage of cell death in the pre
      B ALL lines SEM, RS4;11, and REH when combined with cytarabine, methotrexate, or
      vincristine compared to the chemotherapeutic agents alone. Analysis of DNA strand
      breaks by terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling
      showed that carnosol delayed DNA cleavage in the cells when combined with
      chemotherapeutic drugs. Co-treatment of the cells with carnosol and
      chemotherapeutic drugs did not reduce mitochondrial membrane depolarization
      compared to the drug treatment alone. Time course analysis of caspase-3
      activation by flow cytometry showed co-treatment with carnosol and drugs
      increased the activation of caspase-3 above that observed for the
      chemotherapeutic drugs alone. A lower percentage of caspase-3 positive cells
      progressed to an apoptotic phenotype when co-treated with carnosol and the
      chemotherapeutic drugs compared to drugs alone. These data show that carnosol
      blocks the terminal apoptotic events induced by chemotherapeutic drugs and
      suggest that increased dietary intake of carnosol may potentially decrease the
      effectiveness of some standard chemotherapy treatments used for leukemia.

PMID- 19116880
TI  - Probiotics regulate the expression of COX-2 in intestinal epithelial cells.
AB  - Cyclooxygenase-2 (COX) 2 promotes intestinal wound healing but elicits also
      proinflammatory effects and has been implicated in colorectal carcinogenesis.
      Thus, a balanced expression of COX-2 is essential for intestinal homeostasis.
      This study was designed to evaluate the regulation of COX-2 by probiotic
      organisms and to characterize ligands and receptors involved. Colo320 and SW480
      intestinal epithelial cells (IEC) were stimulated with gastrin or TNF-alpha and
      pre- or coincubated with commensales, bacterial supernatants, or distinct toll
      like receptor (TLR) ligands. COX-2 promoter activity was determined by luciferase
      assays, protein expression by Western blotting, and secretion of prostaglandin
      E(2) (PGE(2)) by ELISA. Commensales differentially regulated COX-2 expression in
      IEC. E. coli Nissle 1917, the probiotic mixture VSL#3, and media conditioned by
      these organisms ameliorated induced COX-2 expression and PGE(2) secretion. Heat
      inactivation and DNase treatment significantly decreased these regulatory
      capacities. Lactobacillus acidophilus, however, significantly increased COX-2
      expression and PGE(2) secretion. TLR agonists differentially ameliorated basal or
      induced COX-2 expression. Distinct probiotics specifically and significantly
      decrease induced COX-2 expression in IEC, most likely mediated by released
      factors and in part by bacterial DNA. A significant involvement of TLRs in these
      regulatory processes remains to be established.

PMID- 19116881
TI  - Conjugated linoleic acid (CLA) inhibits expression of the Spot 14 (THRSP) and
      fatty acid synthase genes and impairs the growth of human breast cancer and
      liposarcoma cells.
AB  - Spot 14 (THRSP, S14) is a nuclear protein involved in the regulation of genes
      required for fatty acid synthesis in normal and malignant mammary epithelial and
      adipose cells. Harvatine and Bauman (1) reported that conjugated linoleic acid
      (CLA) inhibits S14 gene expression in bovine mammary and mouse adipose tissues
      and reduces milk fat production in cows. We hypothesized that CLA inhibits S14
      gene expression in human breast cancer and liposarcoma cells and that this will
      retard their growth. Exposure of T47D breast cancer cells to a mixture of CLA
      isomers reduced the expression of the S14 and fatty acid synthase (FAS) genes.
      The mixture caused a dose-related inhibition of T47D cell growth, as did pure c9,
      t11 and t10, c12-CLA, but not linoleic acid. Similar effects were observed in MDA
      MB-231 breast cancer cells. Provision of 8 mircoM palmitate fully (CLA mix, t10,
      c12-CLA) or partially (c9, t11-CLA) reversed the antiproliferative effect in T47D
      cells. CLA likewise suppressed levels of S14 and FAS mRNAs in liposarcoma cells
      and caused growth inhibition that was prevented by palmitic acid. CLA did not
      affect the growth of nonlipogenic HeLa cells or human fibroblasts. We conclude
      that as in bovine mammary and mouse adipose cells, CLA suppresses S14 and FAS
      gene expression in human breast cancer and liposarcoma cells. Rescue from the
      antiproliferative effect of CLA by palmitic acid indicates that reduced tumor
      lipogenesis is a major mechanism for the anticancer effects of CLA.

PMID- 19116883
TI  - Magnesium deficiency affects mammary epithelial cell proliferation: involvement
      of oxidative stress.
AB  - Low Mg availability reversibly inhibited the growth of mammary epithelial HC11
      cells by increasing the number of cells in the G0/G1 phase of the cell cycle.
      Because low Mg has been reported to promote oxidative reactions, we considered
      that low Mg-dependent growth arrest was mediated by oxidative stress.
      Surprisingly, both dichlorofluorescein-detectable reactive oxygen species and
      hydrogen peroxide-induced oxidative DNA damage were found to be lower in cells
      cultured in low Mg than in cells grown under control or high-Mg conditions. Gene
      expression profiling of low- and high-Mg cells showed the modulation of several
      genes, some regulating cell proliferation. In addition, low Mg cells also
      displayed overexpression of glutathione S-transferase (GST), leading to increased
      enzymatic activity. Of note, GST has been shown to modulate cell growth;
      therefore, we suggest that in low-Mg cells, GST upregulation might have a dual
      role in protecting against oxidative stress and in modulating cell proliferation.

PMID- 19116882
TI  - Growth inhibition and induction of apoptosis of colon cancer cell lines by
      applying marine phospholipid.
AB  - Polyunsaturated fatty acids (PUFAs) exhibit beneficial biological functions in
      carcinogenic processes. We examined the effects of PUFAs in the acid and
      phospholipid forms on three colon cancer cell lines (HT-29, Caco-2, and DLD-1).
      Docosahexaenoic acid (DHA) and eicosapentaenoic (EPA) in both acid and
      phospholipid forms showed growth inhibition effects on experimental colon cancer
      cell lines. But these PUFAs had the strongest growth-inhibitory effect on HT-29
      than Caco-2 and DLD-1. Combined application of PUFAs and sodium butyrate (NaBt)
      increased the growth inhibition. Growth inhibition was apparently caused by
      increased lipid peroxidation. DHA or EPA in combination with NaBt significantly
      increased caspase-3 activity compared to control. DHA and DHA-rich
      phosphatidylcholine decreased Bcl-2 level in HT-29 and Caco-2 cells.

PMID- 19116884
TI  - Involvement of KLF4 in sulforaphane- and iberin-mediated induction of
      p21(waf1/cip1).
AB  - Sulforaphane (SF; 4-methylsulfinylbutyl isothiocyanate), a dietary compound
      derived from broccoli, may exhibit chemopreventive properties by inducing cell
      cycle arrest via induction of cyclin-dependent kinase inhibitor 1A
      (p21(waf1/cip1)), but the exact molecular mechanism has not been determined. Here
      we evaluate the role of the transcription factor Kruppel-like factor 4 (KLF4) in
      mediating the induction of p21(waf1/cip1) and cellular differentiation by SF and
      iberin (IB; 3-methylsulphinyl propyl isothiocyanate), also derived from broccoli.
      Exposure of Caco-2 and Caco-2/TC7 cells to SF and IB increased expression of both
      KLF4 and p21(waf1/cip1), whereas exposure of HT29 cells resulted only in
      induction of p21(waf1/cip1). In Caco-2 cells, small interfering RNA knock down of
      KLF4 expression attenuated induction of p21(waf1/cip1) in response to either SF
      or IB treatment. Contrary to expectation, prolonged exposure to SF reduced
      sucrase isomaltase activity, a marker of small intestinal differentiation in Caco
      2 cells. Additional support for the SF-mediated induction of p21(waf1/cip1) by
      KLF4 was obtained from analyses of gastric tissue of Apc(Min/+) mice following
      acute intervention with SF but not from the analyses of other tissue of the
      intestinal tract. These results suggest that induction of p21(waf1/cip1) by SF or
      IB may be partly mediated by KLF4 in some colon cancer cells and tissues.

PMID- 19116885
TI  - Dietary carbohydrate source alters gene expression profile of intestinal
      epithelium in mice.
AB  - High-sucrose consumption is associated with increased risk of human colon cancer.
      Our previous research indicated that high-sucrose diets (vs. cornstarch) promote
      intestinal epithelial cell proliferation and tumorigenesis as well as increase
      serum glucose and hepatic IGF-I mRNA levels in APC(Min) mice. To examine the role
      of functional pathways, in particular of IGF-I signaling, in sucrose-induced
      intestinal epithelial cell proliferation and tumorigenesis, we examined the
      effects of dietary carbohydrate source (sucrose vs. cornstarch) on gene
      expression in the intestinal epithelium using cDNA microarray and quantitative RT
      PCR analysis. Dietary carbohydrate source significantly (P < 0.05) altered mRNA
      expression of 109 known genes in the small intestinal epithelium, including many
      involved in metabolic pathways. Consumption of high-sucrose diets altered
      expression levels of genes involved in cell adhesion, cell cycle control, and
      transduction signaling, consistent with increased risk of intestinal
      tumorigenesis. High-sucrose intake also affected expression of genes involved in
      IGF-I signaling, including upregulating IGF-II and downregulating IGFBP3, which
      supports our hypothesis that IGF-I signaling could play a role in intestinal
      epithelial cell proliferation and tumorigenesis promoted by high-sucrose
      consumption.

PMID- 19116886
TI  - Prolonged fecal shedding of CTX-M-15-producing Escherichia coli and recurrent
      sepsis in a patient after cord blood stem-cell transplantation.
AB  - An extended-spectrum beta-lactamase (CTX-M-15 type)-producing Escherichia coli
      persisted in the intestinal tract for >5 months in a pediatric patient after cord
      blood stem-cell transplantation and caused 2 episodes of sepsis. The bla(CTX-M
      15) is carried by a large plasmid of approximately 130 kb in size. The prolonged
      shedding of the highly resistant E. coli posed a great challenge to infection
      control and public health.

PMID- 19116887
TI  - Clinical and microbiological effects of biapenem in febrile neutropenic patients
      with hematologic malignancies.

PMID- 19116889
TI  - Effect of chronic psychosocial stress-induced by subordinate colony (CSC) housing
      on brain neuronal activity patterns in mice.
AB  - Chronic subordinate colony (CSC) housing has been recently validated as a murine
      model of chronic psychosocial stress which induces alterations of stress-related
      parameters including decreased body-weight gain and an increased level of anxiety
      in comparison with single housed control (SHC) mice. By using immunohistochemical
      immediate early gene (IEG) mapping we investigated whether CSC housing causes
      alterations in neuronal activation patterns in limbic areas including the
      amygdala, hippocampus, septum and the periaqueductal gray (PAG) and hypothalamic
      paraventricular nucleus (PVN). While CSC housing increased basal Zif-268
      expression in the nucleus accumbens shell compared to SHC, IEG responses to
      subsequent open arm (OA) exposure were attenuated in the ventral and intermediate
      sub-regions of the lateral septum, parvocellular PVN and the dorsal CA3 region of
      the hippocampus of CSC compared with SHC mice. In contrast, a potentiated c-Fos
      response in CSC mice was observed in the dorsomedial PAG after OA exposure.
      Confirming previous findings obtained on the elevated plus-maze, an enhanced
      anxiety-related behavior in CSC compared with SHC mice was also observed during
      OA exposure. In order to investigate the appropriate control conditions for CSC
      housing, group housed control (GHC) mice were additionally included in the
      behavioral testing. Interestingly, GHC as well as CSC mice showed significantly
      less risk assessment/exploratory behavior during OA exposure compared with SHC
      mice indicating that group housing itself is stressful for mice and not an
      adequate control for the CSC paradigm. Overall, CSC housing is an ethologically
      relevant chronic psychosocial stressor which results in an elevated sensitivity
      to a subsequent novel, aversive challenge. However, the CSC-induced increase in
      anxiety-related behavior was accompanied by differences in neuronal activation,
      compared with SHC, in defined sub-regions of brain areas known to be involved in
      the processing of emotionality and stress responses.

PMID- 19116891
TI  - Cathepsins B and D drive hepatic stellate cell proliferation and promote their
      fibrogenic potential.
AB  - Cathepsins have been best characterized in tumorigenesis and cell death and
      implicated in liver fibrosis; however, whether cathepsins directly regulate
      hepatic stellate cell (HSC) activation and proliferation, hence modulating their
      fibrogenic potential, is largely unknown. Here, we show that expression of
      cathepsin B (CtsB) and cathepsin D (CtsD) is negligible in quiescent HSCs but
      parallels the increase of alpha-smooth muscle actin and transforming growth
      factor-beta during in vitro mouse HSC activation. Both cathepsins are necessary
      for HSC transdifferentiation into myofibroblasts, because their silencing or
      inhibition decreased HSC proliferation and the expression of phenotypic markers
      of HSC activation, with similar results observed with the human HSC cell line
      LX2. CtsB inhibition blunted AKT phosphorylation in activated HSCs in response to
      platelet-derived growth factor. Moreover, during in vivo liver fibrogenesis
      caused by CCl(4) administration, CtsB expression increased in HSCs but not in
      hepatocytes, and its inactivation mitigated CCl(4)-induced inflammation, HSC
      activation, and collagen deposition. CONCLUSION: These findings support a
      critical role for cathepsins in HSC activation, suggesting that the antagonism of
      cathepsins in HSCs may be of relevance for the treatment of liver fibrosis.

PMID- 19116892
TI  - PAMAM dendrimers as potential agents against fibrillation of alpha-synuclein, a
      Parkinson's disease-related protein.
AB  - The effect of PAMAM dendrimers (generations G3, G4 and G5) on the fibrillation of
      alpha-synuclein was examined by fluorescence and CD spectroscopy, TEM and SANS.
      PAMAM dendrimers inhibited fibrillation of alpha-synuclein and this effect
      increased both with generation number and PAMAM concentration. SANS showed
      structural changes in the formed aggregates of alpha-synuclein--from cylindrical
      to dense three-dimensional ones--as the PAMAM concentration increased, on account
      of the inhibitory effect. PAMAM also effectively promoted the breaking down of
      pre-existing fibrils of alpha-synuclein. In both processes--that is, inhibition
      and disassociation of fibrils--PAMAM redirected alpha-synuclein to an amorphous
      aggregation pathway.

PMID- 19116893
TI  - Behavior of endothelial cells regulated by a dynamically changed microenvironment
      of biodegradable PLLA-PC.
AB  - The influence of PLLA-PC membranes on the behavior of vascular ECs is studied. It
      was found that the membranes were not cytotoxic. The cell adhesion and spread on
      PLLA-PC 30/1 were initially depressed. After 1 d, however, cells attached and
      spread on the copolymer, and proliferated beyond 2 d. To elucidate the mechanism
      of this behavior, the surface morphology and the degradation products of the
      PLLA/PC 30/1 membrane during the culture period were tested, and Fg adsorption to
      the membranes was examined. It is concluded that the behavior of ECs can be
      regulated by a dynamically changed microenvironment of the PLLA-PC membrane. PLLA
      PC copolymers might therefore serve as a novel material for tissue engineering.

PMID- 19116894
TI  - Interaction of ionic liquids with polysaccharides, 8 - synthesis of cellulose
      sulfates suitable for polyelectrolyte complex formation.
AB  - Water-soluble CS with different DS were synthesized by homogeneous conversion of
      cellulose (microcrystalline cellulose and spruce sulfite pulp) with different
      sulfating agents in the ionic liquids BMIMCl, AMIMCl and EMIMAc. N,N
      Dimethylformamide was used as a dipolar aprotic co-solvent in order to improve
      the miscibility of the reaction mixture. The CS prepared by the new homogeneous
      reaction pathway were studied towards the formation of PEC capsules. CS obtained
      from SSP formed mechanically stable PEC capsules with PolyDADMAC. Exploiting this
      method, the microencapsulation of glucose oxidase was studied and enzyme activity
      tests were performed with encapsulated GOD.

PMID- 19116888
TI  - Stress, depression and cardiovascular dysregulation: a review of neurobiological
      mechanisms and the integration of research from preclinical disease models.
AB  - Bidirectional associations between mood disorders and cardiovascular diseases are
      extensively documented. However, the precise physiological and biochemical
      mechanisms that underlie such relationships are not well understood. This review
      focuses on the neurobiological processes and mediators that are common to both
      mood and cardiovascular disorders. The discussion places an emphasis on the role
      of exogenous stressors in addition to: (a) neuroendocrine and neurohumoral
      changes involving dysfunction of the hypothalamic-pituitary-adrenal axis and the
      activation of the renin-angiotensin-aldosterone system, (b) immune alterations
      including activation of pro-inflammatory cytokines, (c) autonomic and
      cardiovascular dysregulation including increased sympathetic drive, withdrawal of
      parasympathetic tone, cardiac rate and rhythm disturbances, and altered
      baroreceptor reflex function, (d) central neurotransmitter system dysfunction
      involving the dopamine, norepinephrine and serotonin systems, and (e) behavioral
      changes including fatigue and physical inactivity. The review also discusses
      experimental investigations using preclinical disease models to elucidate the
      neurobiological mechanisms underlying the link between mood disorders and
      cardiovascular disease. These include: (a) the chronic mild stress model of
      depression, (b) a model of congestive heart failure, (c) a model of
      cardiovascular deconditioning, (d) pharmacological manipulations of body fluid
      and sodium balance, and (e) pharmacological manipulations of the central
      serotonergic system. In combination with an extensive human research literature,
      the investigation of mechanisms underlying mood and cardiovascular regulation
      using animal models will enhance understanding the association between depression
      and cardiovascular disease. This will ultimately promote the development of
      better treatments and interventions for individuals with co-morbid psychological
      and somatic pathologies.

PMID- 19116895
TI  - Polymers in life sciences.

PMID- 19116897
TI  - Modulation of lubricin biosynthesis and tissue surface properties following
      cartilage mechanical injury.
AB  - OBJECTIVE: To evaluate the effects of injurious compression on the biosynthesis
      of lubricin at different depths within articular cartilage and to examine
      alterations in structure and function of the articular surface following
      mechanical injury. METHODS: Bovine cartilage explants were subdivided into level
      1, with intact articular surface, and level 2, containing middle and deep zone
      cartilage. Following mechanical injury, lubricin messenger RNA (mRNA) levels were
      monitored by quantitative reverse transcriptase-polymerase chain reaction, and
      soluble or cartilage-associated lubricin protein was analyzed by Western blotting
      and immunohistochemistry. Cartilage morphology was assessed by histologic
      staining, and tissue functionality was assessed by friction testing. RESULTS: Two
      days after injury, lubricin mRNA expression was up-regulated approximately 3-fold
      for level 1 explants and was down-regulated for level 2 explants. Lubricin
      expression in level 1 cartilage returned to control levels after 6 days in
      culture. Similarly, lubricin protein synthesis and secretion increased in
      response to injury for level 1 explants and decreased for level 2 cartilage.
      Histologic staining revealed changes in the articular surface of level 1 explants
      following injury, with respect to glycosaminoglycan and collagen content. Injured
      level 1 explants displayed an increased coefficient of friction relative to
      controls. CONCLUSION: Our findings indicate that increased lubricin biosynthesis
      appears to be an early transient response of surface-layer cartilage to injurious
      compression. However, distinct morphologic changes occur with injury that appear
      to compromise the frictional properties of the tissue.

PMID- 19116896
TI  - Sodium oxybate relieves pain and improves function in fibromyalgia syndrome: a
      randomized, double-blind, placebo-controlled, multicenter clinical trial.
AB  - OBJECTIVE: To evaluate the safety and efficacy of sodium oxybate for management
      of the symptoms of fibromyalgia syndrome (FMS). METHODS: Patients with FMS
      (according to the American College of Rheumatology 1990 criteria) were
      randomized, after discontinuing their prestudy medications for FMS, to receive
      4.5 gm or 6 gm of sodium oxybate or matching placebo once per night for 8 weeks.
      The primary outcome variable (POV) was a composite score for changes from
      baseline in 3 coprimary self-report measures: patient's pain rating (in daily
      electronic diaries) on a visual analog scale (PVAS), the Fibromyalgia Impact
      Questionnaire (FIQ) score, and the Patient Global Impression of Change (PGI-C). A
      beneficial response rate for the POV composite score was defined as >or=20%
      improvement in the PVAS and FIQ scores plus a rating of "much better" or "very
      much better" on the PGI-C. Secondary measures included subjective sleep outcomes
      (on the Jenkins Scale for Sleep) and quality-of-life measures. The analyses were
      based on an intent-to-treat (ITT) population. RESULTS: The ITT population
      included 188 patients with FMS, 78% of whom completed the trial. Significant
      benefit was observed with both dosages of sodium oxybate, according to changes in
      the POV and subjective sleep quality. Improvements in the PVAS score were
      significantly correlated with sleep outcomes. Sodium oxybate was well tolerated
      overall; dose-related nausea (<or=28% of patients) and dizziness (<or=18% of
      patients) tended to resolve with continued therapy. CONCLUSION: Sodium oxybate
      therapy was well tolerated and significantly improved the symptoms of FMS.
      Further study of sodium oxybate as a novel therapeutic option for FMS is
      warranted.

PMID- 19116898
TI  - Clinical Images: Lumbar spondylolisthesis caused by tophaceous gout.

PMID- 19116899
TI  - Tumor necrosis factor receptor-associated periodic syndrome: toward a molecular
      understanding of the systemic autoinflammatory diseases.

PMID- 19116900
TI  - Novel markers of inflammation identified in tumor necrosis factor receptor
      associated periodic syndrome (TRAPS) by transcriptomic analysis of effects of
      TRAPS-associated tumor necrosis factor receptor type I mutations in an
      endothelial cell line.
AB  - OBJECTIVE: To analyze the effects of tumor necrosis factor receptor-associated
      periodic syndrome (TRAPS)-associated mutant tumor necrosis factor receptor type I
      (TNFRI) expression in a cell type directly relevant to the inflammation in TRAPS,
      and to identify novel markers associated with mutant TNFRI expression. METHODS:
      Transcriptome analysis on 30,000 human genes was performed on SK-Hep-1 human
      endothelial cells transfected with either wild-type (WT) or TRAPS-associated
      mutant TNFRI. Quantitative reverse transcriptase-polymerase chain reaction and
      protein expression levels measured by enzyme-linked immunosorbent assay verified
      transcriptional changes for selected genes both in supernatants from cells
      expressing mutant TNFRI and in patient plasma. RESULTS: Cells expressing mutant
      TNFRI showed up-regulation of multiple proinflammatory genes relative to WT
      transfectants, including genes for pentraxin 3, granulocyte-macrophage colony
      stimulating factor, granulocyte colony-stimulating factor, CCL2, and CCL5, which
      were also expressed as proteins. In addition, the expression of most of these
      markers was increased in the plasma and peripheral blood mononuclear cells from
      TRAPS patients relative to those from healthy controls. The cysteine mutations
      (C33Y and C52F), which are associated with a more severe clinical phenotype,
      induced more genes than the low-penetrance mutation R92Q, which is associated
      with a milder phenotype. The expression of most genes was induced by a death
      domain (DD)-dependent mechanism, since they were not induced by expression of
      TNFRI mutants with an inactivated DD. CONCLUSION: TRAPS-associated TNFRI mutants
      induce the expression of multiple genes encoding inflammatory molecules, cellular
      receptors, transcription factors, and regulators of apoptosis in endothelial
      cells that require the cytoplasmic signaling properties of the receptor.
      Different mutants have specific expression profiles, indicating mutation-specific
      effects. The expression of some of these markers was also elevated in samples
      from TRAPS patients.

PMID- 19116901
TI  - Independent association of rheumatoid arthritis with increased left ventricular
      mass but not with reduced ejection fraction.
AB  - OBJECTIVE: Rheumatoid arthritis (RA) is a chronic inflammatory disease associated
      with premature atherosclerosis, vascular stiffening, and heart failure. This
      study was undertaken to investigate whether RA is associated with underlying
      structural and functional abnormalities of the left ventricle (LV). METHODS:
      Eighty-nine RA patients without clinical cardiovascular disease and 89 healthy
      matched controls underwent echocardiography, carotid ultrasonography, and radial
      tonometry to measure arterial stiffness. RA patients and controls were similar in
      body size, hypertension and diabetes status, and cholesterol level. RESULTS: LV
      diastolic diameter (4.92 cm versus 4.64 cm; P<0.001), mass (136.9 gm versus 121.7
      gm; P=0.004 or 36.5 versus 32.9 gm/m2.7; P=0.01), ejection fraction (71% versus
      67%; P<0.001), and prevalence of LV hypertrophy (18% versus 6.7%; P=0.023) were
      all higher among RA patients versus controls. In multivariate analysis, presence
      of RA was an independent correlate of LV mass (P=0.004). Furthermore, RA was
      independently associated with presence of LV hypertrophy (odds ratio 4.14 [95%
      confidence interval 1.24, 13.80], P=0.021). Among RA patients, age at diagnosis
      and disease duration were independently related to LV mass. RA patients with LV
      hypertrophy were older and had higher systolic pressure, damage index scores, C
      reactive protein levels, homocysteine levels, and arterial stiffness compared
      with those without LV hypertrophy. CONCLUSION: The present results demonstrate
      that RA is associated with increased LV mass. Disease duration is independently
      related to increased LV mass, suggesting a pathophysiologic link between chronic
      inflammation and LV hypertrophy. In contrast, LV systolic function is preserved
      in RA patients, indicating that systolic dysfunction is not an intrinsic feature
      of RA.

PMID- 19116902
TI  - Systems biology analysis of Sjogren's syndrome and mucosa-associated lymphoid
      tissue lymphoma in parotid glands.
AB  - OBJECTIVE: To identify key target genes and activated signaling pathways
      associated with the pathogenesis of Sjogren's syndrome (SS) by conducting a
      systems analysis of parotid glands manifesting primary SS or primary SS/mucosa
      associated lymphoid tissue (MALT) lymphoma phenotypes. METHODS: A systems biology
      approach was used to analyze parotid gland tissue samples obtained from patients
      with primary SS, patients with primary SS/MALT lymphoma, and subjects without
      primary SS (non-primary SS controls). The tissue samples were assessed
      concurrently by gene-expression microarray profiling and proteomics analysis,
      followed by weighted gene-coexpression network analysis. RESULTS: Gene
      coexpression modules related to primary SS and primary SS/MALT lymphoma were
      significantly enriched with genes known to be involved in the immune/defense
      response, apoptosis, cell signaling, gene regulation, and oxidative stress.
      Detailed functional pathway analyses indicated that primary SS-associated modules
      were enriched with genes involved in proteasome degradation, apoptosis, signal
      peptides of the class I major histocompatibility complex (MHC), complement
      activation, cell growth and death, and integrin-mediated cell adhesion, while
      primary SS/MALT lymphoma-associated modules were enriched with genes involved in
      translation, ribosome biogenesis and assembly, proteasome degradation, class I
      MHC signal peptides, the G13 signaling pathway, complement activation, and
      integrin-mediated cell adhesion. Combined analyses of gene expression and
      proteomics data implicated 6 highly connected "hub" genes for distinguishing
      primary SS from non-primary SS, and 8 hub genes for distinguishing primary
      SS/MALT lymphoma from primary SS. CONCLUSION: Systems biology analyses of the
      parotid glands from patients with primary SS and those with primary SS/MALT
      lymphoma revealed pathways and molecular targets associated with disease
      pathogenesis. The identified gene modules/pathways provide further insights into
      the molecular mechanisms of primary SS and primary SS/MALT lymphoma. The
      identified disease-hub genes represent promising targets for therapeutic
      intervention, diagnosis, and prognosis.

PMID- 19116904
TI  - Differential expression of alphaB-crystallin and evidence of its role as a
      mediator of matrix gene expression in osteoarthritis.
AB  - OBJECTIVE: Alpha B-crystallin belongs to the family of small heat-shock proteins
      (HSPs). The role of this protein family in chondrocytes is not well understood.
      The present study was undertaken to investigate expression levels of alphaB
      crystallin in chondrocytes isolated from healthy subjects and patients with
      osteoarthritis (OA), and to explore the functional role of this potentially
      interesting protein in chondrocyte metabolism. METHODS: Western blot and real
      time reverse transcriptase-polymerase chain reaction (RT-PCR) analyses were
      performed to determine expression levels of alphaB-crystallin in healthy and OA
      chondrocytes cultured in alginate beads. RNA interference-mediated gene knockdown
      was used to explore the role of this small HSP in chondrocyte biology, by
      transfecting low concentrations of small interfering RNA (siRNA) in cultured
      chondrocytes. RESULTS: We initially identified alphaB-crystallin as a small HSP
      that was differentially expressed between healthy and OA-affected chondrocytes.
      The decreased abundance of this protein in OA chondrocytes was confirmed by
      Western blotting. Moreover, real-time RT-PCR confirmed the differential
      expression between chondrocytes isolated from visibly intact and visibly damaged
      zones of OA cartilage. The proinflammatory cytokines interleukin-1beta and tumor
      necrosis factor alpha both down-regulated alphaB-crystallin expression.
      Transfection of low concentrations of siRNA in cultured chondrocytes resulted in
      efficient knockdown of alphaB-crystallin gene expression. This was accompanied by
      altered expression of the chondrocyte-specific bone morphogenetic protein 2,
      aggrecan, and type II collagen genes. CONCLUSION: The present findings identify
      the small HSP alphaB-crystallin as a novel mediator of chondrocyte matrix gene
      expression that may contribute to altered chondrocyte metabolism during the
      development of OA.

PMID- 19116903
TI  - Effect of interleukin-1beta on osteogenic protein 1-induced signaling in adult
      human articular chondrocytes.
AB  - OBJECTIVE: Two major receptor-activated Smad (R-Smad) signaling pathways, bone
      morphogenetic protein (BMP) and MAPK, were examined in a model of interleukin
      1beta (IL-1beta)-induced cartilage degeneration to investigate the effect of IL
      1beta on osteogenic protein 1 (OP-1) signaling in adult human articular
      chondrocytes. METHODS: Chondrocytes from the ankles of 26 normal human donors
      were cultured in high-density monolayers in serum-free medium. The effect of IL
      1beta on BMP receptors was studied by reverse transcription-polymerase chain
      reaction and flow cytometry. Phosphorylation of R-Smads was tested in cells
      treated with IL-1beta (10 ng/ml), OP-1 (100 ng/ml), or the combination of IL
      1beta and OP-1. Cell lysates were analyzed by Western blotting with polyclonal
      antibodies against 2 R-Smad phosphorylation sites (BMP- and MAPK-mediated) or
      with total, nonphosphorylated R-Smad as a control. To identify which MAPKs play a
      role in IL-1beta activation of the linker region, chondrocytes were preincubated
      with specific MAPK inhibitors (PD98059 for MAP/ERK, SP600125 for JNK, and
      SB203580 for p38). RESULTS: IL-1beta reduced the number of activin receptor-like
      kinase 2 (ALK-2) and ALK-3 receptors, inhibited expression of Smad1 and Smad6,
      delayed and prematurely terminated the onset of OP-1-mediated R-Smad
      phosphorylation, and affected nuclear translocation of R-Smad/Smad4 complexes.
      The alternative phosphorylation of R-Smad in the linker region via the MAPK
      pathway (primarily p38 and JNK) was observed to be a possible mechanism through
      which IL-1beta offsets OP-1 signaling and the response to OP-1. Conversely, OP-1
      was found to directly inhibit phosphorylation of p38. CONCLUSION: These findings
      describe new mechanisms of the crosstalk between OP-1 and IL-1beta in
      chondrocytes. The study also identifies potential targets for therapeutic
      interventions in the treatment of cartilage-degenerative processes.

PMID- 19116906
TI  - Successful treatment of idiopathic recurrent pericarditis in children with
      interleukin-1beta receptor antagonist (anakinra): an unrecognized
      autoinflammatory disease?
AB  - Recurrent pericarditis occurs in association with various medical conditions, but
      in most cases the condition appears to be idiopathic. Although high-dose steroid
      treatment is often effective, it may have serious side effects. Herein we
      describe 3 children with recurrent pericarditis who were treated at our hospital,
      during flares, with the interleukin-1beta receptor antagonist anakinra, with
      immediate response. Pericarditis recurred when anakinra treatment was
      discontinued, and no further episodes occurred after it was resumed. Idiopathic
      recurrent pericarditis shares several features with autoinflammatory diseases,
      and anakinra has been efficacious in the treatment of the latter diseases. The
      findings in these patients suggest that idiopathic recurrent pericarditis may be
      a previously unrecognized autoinflammatory disease.

PMID- 19116905
TI  - Blocking vascular endothelial growth factor with soluble Flt-1 improves the
      chondrogenic potential of mouse skeletal muscle-derived stem cells.
AB  - OBJECTIVE: To investigate the effect of vascular endothelial growth factor (VEGF)
      stimulation and the effect of blocking VEGF with its antagonist, soluble Flt-1
      (sFlt-1), on chondrogenesis, using muscle-derived stem cells (MDSCs) isolated
      from mouse skeletal muscle. METHODS: The direct effect of VEGF on the in vitro
      chondrogenic ability of mouse MDSCs was tested using a pellet culture system,
      followed by real-time quantitative polymerase chain reaction (PCR) and histologic
      analyses. Next, the effect of VEGF on chondrogenesis within the synovial joint
      was tested, using genetically engineered MDSCs implanted into rat osteochondral
      defects. In this model, MDSCs transduced with a retroviral vector to express bone
      morphogenetic protein 4 (BMP-4) were coimplanted with MDSCs transduced to express
      either VEGF or sFlt-1 (a VEGF antagonist) to provide a gain- and loss-of-function
      experimental design. Histologic scoring was used to compare cartilage formation
      among the treatment groups. RESULTS: Hyaline-like cartilage matrix production was
      observed in both VEGF-treated and VEGF-blocked (sFlt-1-treated) pellet cultures,
      but quantitative PCR revealed that sFlt-1 treatment improved the expression of
      chondrogenic genes in MDSCs that were stimulated to undergo chondrogenic
      differentiation with BMP-4 and transforming growth factor beta3 (TGFbeta3). In
      vivo testing of articular cartilage repair showed that VEGF-transduced MDSCs
      caused an arthritic change in the knee joint, and sFlt-1 improved the MDSC
      mediated repair of articular cartilage, compared with BMP-4 alone. CONCLUSION:
      Soluble Flt-1 gene therapy improved the BMP-4- and TGFbeta3-induced chondrogenic
      gene expression of MDSCs in vitro and improved the persistence of articular
      cartilage repair by preventing vascularization and bone invasion into the
      repaired articular cartilage.

PMID- 19116907
TI  - Association of the TRAF1/C5 locus with increased mortality, particularly from
      malignancy or sepsis, in patients with rheumatoid arthritis.
AB  - OBJECTIVE: Recent genome-wide association studies have identified TRAF1/C5 as a
      rheumatoid arthritis (RA) susceptibility locus. Tumor necrosis factor receptor
      associated factor 1 (TRAF1) has been implicated in the regulation of
      antiapoptotic pathways, whereas C5 has a well-established role in defense against
      infection. The purpose of this study was to examine the association of the
      TRAF1/C5 locus with death in patients with RA. METHODS: Genomic DNA samples were
      collected from a prospective cohort of 400 RA patients. TRAF1/C5 rs3761847 was
      identified using real-time polymerase chain reaction and melting curve analyses.
      The association of TRAF1/C5 rs3761847 alleles with the risk of death was assessed
      using Cox proportional hazards regression analyses. RESULTS: TRAF1/C5 rs3761847
      GG homozygote status was associated with an increased risk of death (hazard ratio
      3.96 [95% confidence interval 1.24-12.6], P=0.020) as compared with AA homozygote
      status. The excess mortality was attributed to deaths due to malignancies and
      sepsis but not cardiovascular disease (CVD). This polymorphism was one of the
      strongest predictors of death in RA (for TRAF1/C5 GG versus AA, hazard ratio 3.85
      [95% confidence interval 1.18-12.59], P=0.026) alongside the erythrocyte
      sedimentation rate, triglyceride level, prednisolone use, and age. CONCLUSION:
      The risk of death in RA is increased in TRAF1/C5 rs3761847 GG homozygotes and
      appears to be independent of RA activity and severity as well as comorbidities
      relevant to CVD. If this finding is replicated in future studies, TRAF1/C5
      genotyping could identify patients at increased risk of death, particularly death
      due to malignancy or sepsis.

PMID- 19116908
TI  - Stimulation of nicotinic acetylcholine receptors attenuates collagen-induced
      arthritis in mice.
AB  - OBJECTIVE: The parasympathetic nervous system, through the vagus nerve, can down
      regulate inflammation in vivo by decreasing the release of cytokines, including
      tumor necrosis factor alpha (TNFalpha), by activated macrophages. The vagus nerve
      may exert antiinflammatory actions via a specific effect of its principal
      neurotransmitter, acetylcholine, on the alpha7 subunit of nicotinic acetylcholine
      receptors (alpha7nAChR) on macrophages. The present study was undertaken to
      obtain insight into the role of the cholinergic antiinflammatory pathway in
      arthritis. METHODS: To inhibit the cholinergic antiinflammatory pathway, mice
      were subjected to unilateral cervical vagotomy or sham surgery, after which
      arthritis was induced with type II collagen. In a separate study, nicotine was
      added to the drinking water of mice with collagen-induced arthritis (CIA). In
      addition, we investigated the effects of intraperitoneally (IP)-injected nicotine
      and the specific alpha7nAChR agonist AR-R17779. RESULTS: Clinical arthritis was
      exacerbated by vagotomy and ameliorated by oral nicotine administration.
      Moreover, oral nicotine inhibited bone degradation and reduced TNFalpha
      expression in synovial tissue. Both IP-injected nicotine and AR-R17779
      ameliorated clinical arthritis and reduced synovial inflammation. This was
      accompanied by a reduction of TNFalpha levels in both plasma and synovial tissue.
      The effect of AR-R17779 was more potent compared with that of nicotine and was
      associated with delayed onset of the disease as well as with protection against
      joint destruction. CONCLUSION: These data provide the first evidence of a role of
      the cholinergic antiinflammatory pathway in the murine CIA model of rheumatoid
      arthritis.

PMID- 19116910
TI  - The future of folic acid antagonist therapy in rheumatoid arthritis.

PMID- 19116909
TI  - Association of the IL2RA/CD25 gene with juvenile idiopathic arthritis.
AB  - OBJECTIVE: IL2RA/CD25, the gene for interleukin-2 receptor alpha, is emerging as
      a general susceptibility gene for autoimmune diseases because of its role in the
      development and function of regulatory T cells and the association of single
      nucleotide polymorphisms (SNPs) within this gene with type 1 diabetes mellitus
      (DM), Graves' disease, rheumatoid arthritis (RA), and multiple sclerosis (MS).
      The aim of this study was to determine whether SNPs within the IL2RA/CD25 gene
      are associated with juvenile idiopathic arthritis (JIA). METHODS: Three SNPs
      within the IL2RA/CD25 gene, that previously showed evidence of an association
      with either RA, MS, or type 1 DM, were selected for genotyping in UK JIA cases
      (n=654) and controls (n=3,849). Data for 1 SNP (rs2104286) were also available
      from North American JIA cases (n=747) and controls (n=1,161). Association
      analyses were performed using Plink software. Odds ratios (ORs) and 95%
      confidence intervals (95% CIs) were calculated. RESULTS: SNP rs2104286 within the
      IL2RA/CD25 gene was significantly associated with UK JIA cases (OR for the allele
      0.76 [95% CI 0.66-0.88], P for trend=0.0002). A second SNP (rs41295061) also
      showed modest evidence for association with JIA (OR 0.80 [95% CI 0.63-1.0],
      P=0.05). Association with rs2104286 was convincingly replicated in the North
      American JIA cohort (OR 0.84 [95% CI 0.65-0.99], P for trend=0.05). Meta-analysis
      of the 2 cohorts yielded highly significant evidence of association with JIA (OR
      0.76 [95% CI 0.62-0.88], P=4.9x10(-5)). CONCLUSION: These results provide strong
      evidence that the IL2RA/CD25 gene represents a JIA susceptibility locus. Further
      investigation of the gene using both genetic and functional approaches is now
      required.

PMID- 19116911
TI  - Naturally acquired microchimerism: for better or for worse.

PMID- 19116913
TI  - Folate receptor beta as a potential delivery route for novel folate antagonists
      to macrophages in the synovial tissue of rheumatoid arthritis patients.
AB  - OBJECTIVE: To determine the expression of folate receptor beta (FRbeta) in
      synovial biopsy tissues and peripheral blood lymphocytes from rheumatoid
      arthritis (RA) patients and to identify novel folate antagonists that are more
      selective in the targeting and internalization of FRbeta than methotrexate (MTX).
      METHODS: Immunohistochemistry and computer-assisted digital imaging analyses were
      used for the detection of FRbeta protein expression on immunocompetent cells in
      synovial biopsy samples from RA patients with active disease and in
      noninflammatory control synovial tissues. FRbeta messenger RNA (mRNA) levels were
      determined by reverse transcription-polymerase chain reaction analysis. Binding
      affinities of FRbeta for folate antagonists were assessed by competition
      experiments for 3H-folic acid binding on FRbeta-transfected cells. Efficacy of
      FRbeta-mediated internalization of folate antagonists was evaluated by assessment
      of antiproliferative effects against FRbeta-transfected cells. RESULTS:
      Immunohistochemical staining of RA synovial tissue showed high expression of
      FRbeta on macrophages in the intimal lining layer and synovial sublining, whereas
      no staining was observed in T cell areas or in control synovial tissue.
      Consistently, FRbeta mRNA levels were highest in synovial tissue extracts and RA
      monocyte-derived macrophages, but low in peripheral blood T cells and monocytes.
      Screening of 10 new-generation folate antagonists revealed 4 compounds for which
      FRbeta had a high binding affinity (20-77-fold higher than for MTX). One of
      these, the thymidylate synthase inhibitor BCG 945, displayed selective targeting
      against FRbeta-transfected cells. CONCLUSION: Abundant FRbeta expression on
      activated macrophages in synovial tissue from RA patients deserves further
      exploration for selective therapeutic interventions with high-affinity-binding
      folate antagonists, of which BCG 945 may be a prototypical representative.

PMID- 19116914
TI  - Requirement of transforming growth factor beta-activated kinase 1 for
      transforming growth factor beta-induced alpha-smooth muscle actin expression and
      extracellular matrix contraction in fibroblasts.
AB  - OBJECTIVE: Fibrosis is believed to occur through normal tissue remodeling failing
      to terminate. Tissue repair intimately involves the ability of fibroblasts to
      contract extracellular matrix (ECM), and enhanced ECM contraction is a hallmark
      of fibrotic cells in various conditions, including scleroderma. Some fibrogenic
      transcriptional responses to transforming growth factor beta (TGFbeta), including
      alpha-smooth muscle actin (alpha-SMA) expression and ECM contraction, require
      focal adhesion kinase/Src (FAK/Src). The present study was undertaken to assess
      whether TGFbeta-activated kinase 1 (TAK1) acts downstream of FAK/Src to mediate
      fibrogenic responses in fibroblasts. METHODS: We used microarray, real-time
      polymerase chain reaction, Western blot, and collagen gel contraction assays to
      assess the ability of wild-type and TAK1-knockout fibroblasts to respond to
      TGFbeta1. RESULTS: The ability of TGF to induce TAK1 was blocked by the FAK/Src
      inhibitor PP2. JNK phosphorylation in response to TGFbeta1 was impaired in the
      absence of TAK1. TGFbeta could not induce matrix contraction or expression of a
      group of fibrotic genes, including alpha-SMA, in the absence of TAK1. CONCLUSION:
      These results suggest that TAK1 operates downstream of FAK/Src in mediating
      fibrogenic responses and that targeting of TAK1 may be a viable antifibrotic
      strategy in the treatment of certain disorders, including scleroderma.

PMID- 19116915
TI  - Genetic, immunologic, and immunohistochemical analysis of the programmed death
      1/programmed death ligand 1 pathway in human systemic lupus erythematosus.
AB  - OBJECTIVE: A putative regulatory intronic polymorphism (PD1.3) in the programmed
      death 1 (PD-1) gene, a negative regulator of T cells involved in peripheral
      tolerance, is associated with increased risk for systemic lupus erythematosus
      (SLE). We undertook this study to determine the expression and function of PD-1
      in SLE patients. METHODS: We genotyped 289 SLE patients and 256 matched healthy
      controls for PD1.3 by polymerase chain reaction-restriction fragment length
      polymorphism analysis. Expression of PD-1 and its ligand, PDL-1, was determined
      in peripheral blood lymphocytes and in renal biopsy samples by flow cytometry and
      immunohistochemistry. A crosslinker of PD-1 was used to assess its effects on
      anti-CD3/anti-CD28-induced T cell proliferation and cytokine production. RESULTS:
      SLE patients had an increased frequency of the PD1.3 polymorphism (30.1%, versus
      18.4% in controls; P=0.006), with the risk A allele conferring decreased
      transcriptional activity in transfected Jurkat cells. Patients homozygous for
      PD1.3-but not patients heterozygous for PD1.3-had reduced basal and induced PD-1
      expression on activated CD4+ T cells. In autologous mixed lymphocyte reactions
      (AMLRs), SLE patients had defective PD-1 induction on activated CD4+ cells;
      abnormalities were more pronounced among homozygotes. PD-1 was detected within
      the glomeruli and renal tubules of lupus nephritis patients, while PDL-1 was
      expressed by the renal tubules of both patients and controls. PD-1 crosslinking
      suppressed proliferation and cytokine production in both normal and lupus T
      cells; addition of serum from patients with active SLE significantly ameliorated
      this effect on proliferation. CONCLUSION: SLE patients display aberrant
      expression and function of PD-1 attributed to both direct and indirect effects.
      The expression of PD-1/PDL-1 in renal tissue and during AMLRs suggests an
      important role in regulating peripheral T cell tolerance.

PMID- 19116916
TI  - Reply to letter by Volkman commenting on the possible onset of seronegative
      disease in Lyme arthritis.

PMID- 19116918
TI  - Clinical image: Brain perfusion single-photon-emission computed tomography
      findings in a patient with an asymmetric fibromyalgia syndrome.

PMID- 19116917
TI  - Identification of the core element responsive to runt-related transcription
      factor 2 in the promoter of human type X collagen gene.
AB  - OBJECTIVE: Type X collagen and runt-related transcription factor 2 (RUNX-2) are
      known to be important for chondrocyte hypertrophy during skeletal growth and
      repair and development of osteoarthritis (OA) in mice. Aiming at clinical
      application, this study was undertaken to investigate transcriptional regulation
      of human type X collagen by RUNX-2 in human cells. METHODS: Localization of type
      X collagen and RUNX-2 was determined by immunohistochemistry, and their
      functional interaction was examined in cultured mouse chondrogenic ATDC-5 cells.
      Promoter activity of the human type X collagen gene (COL10A1) was examined in
      human HeLa, HuH7, and OUMS27 cells transfected with a luciferase gene containing
      a 4.5-kb promoter and fragments. Binding to RUNX-2 was examined by
      electrophoretic mobility shift assay and chromatin immunoprecipitation. RESULTS:
      RUNX-2 and type X collagen were co-localized in mouse limb cartilage and bone
      fracture callus. Gain and loss of function of RUNX-2 revealed that RUNX-2 is
      essential for type X collagen expression and terminal differentiation of
      chondrocytes. Human COL10A1 promoter activity was enhanced by RUNX-2 alone and
      more potently by RUNX-2 in combination with the coactivator core-binding factor
      beta in all 3 human cell lines examined. Deletion, mutagenesis, and tandem repeat
      analyses identified the core responsive element as the region between -89 and -60
      bp (termed the hypertrophy box [HY box]), which showed specific binding to RUNX
      2. Other putative RUNX-2 binding motifs in the human COL10A1 promoter did not
      respond to RUNX-2 in human cells. CONCLUSION: Our findings indicate that the HY
      box is the core element responsive to RUNX-2 in human COL10A1 promoter. Studies
      on molecular networks related to RUNX-2 and the HY box will lead to treatments of
      skeletal growth retardation, bone fracture, and OA.

PMID- 19116919
TI  - Inflammatory lesions of the spine on magnetic resonance imaging predict the
      development of new syndesmophytes in ankylosing spondylitis: evidence of a
      relationship between inflammation and new bone formation.
AB  - OBJECTIVE: To determine whether a vertebral corner that demonstrates an active
      corner inflammatory lesion (CIL) on magnetic resonance imaging (MRI) in patients
      with ankylosing spondylitis (AS) is more likely to evolve into a de novo
      syndesmophyte visible on plain radiography than is a vertebral corner that
      demonstrates no active inflammation on MRI. METHODS: MRI scans and plain
      radiographs were obtained for 29 patients recruited into randomized placebo
      controlled trials of anti-tumor necrosis factor alpha (anti-TNFalpha) therapy.
      MRI was conducted at baseline, 12 or 24 weeks (n=29), and 2 years (n=22), while
      radiography was conducted at baseline and 2 years. A persistent CIL was defined
      as a CIL that was found on all available scans. A resolved CIL was defined as
      having completely disappeared on either the second or third scan. A validation
      cohort consisted of 41 AS patients followed up prospectively. Anonymized MRIs
      were assessed independently by 3 readers who were blinded with regard to
      radiographic findings. RESULTS: New syndesmophytes developed significantly more
      frequently in vertebral corners with inflammation (20%) than in those without
      inflammation (5.1%) seen on baseline MRI (P<or=0.008 for all reader pairs). They
      also developed more frequently in vertebral corners where inflammation had
      resolved than in those where inflammation persisted after anti-TNF treatment.
      This was confirmed in the analysis of the prospective cohort, in which
      significantly more vertebral corners with inflammation (14.3%) compared with
      those without inflammation (2.9%) seen on baseline MRI developed new
      syndesmophytes (P<or=0.003 for all reader pairs). CONCLUSION: Our findings
      indicate that a syndesmophyte is more likely to develop from a prior inflammatory
      lesion, supporting a relationship between inflammation and ankylosis.

PMID- 19116920
TI  - Role of the NOD2 genotype in the clinical phenotype of Blau syndrome and early
      onset sarcoidosis.
AB  - OBJECTIVE: Blau syndrome and its sporadic counterpart, early-onset sarcoidosis
      (EOS), share a phenotype featuring the symptom triad of skin rash, arthritis, and
      uveitis. This systemic inflammatory granulomatosis is associated with mutations
      in the NOD2 gene. The aim of this study was to describe the clinical
      manifestations of Blau syndrome/EOS in Japanese patients and to determine whether
      the NOD2 genotype and its associated basal NF-kappaB activity predict the Blau
      syndrome/EOS clinical phenotype. METHODS: Twenty Japanese patients with Blau
      syndrome/EOS and NOD2 mutations were recruited. Mutated NOD2 was categorized
      based on its basal NF-kappaB activity, which was defined as the ratio of NF
      kappaB activity without a NOD2 ligand, muramyldipeptide, to NF-kappaB activity
      with muramyldipeptide. RESULTS: All 9 mutations, including E383G, a novel
      mutation that was identified in 20 patients with Blau syndrome/EOS, were detected
      in the centrally located NOD region and were associated with ligand-independent
      NF-kappaB activation. The median age of the patients at disease onset was 14
      months, although in 2 patients in Blau syndrome families (with mutations R334W
      and E383G, respectively) the age at onset was 5 years or older. Most patients
      with Blau syndrome/EOS had the triad of skin, joint, and ocular symptoms, the
      onset of which was in this order. Clinical manifestations varied even among
      familial cases and patients with the same mutations. There was no clear
      relationship between the clinical phenotype and basal NF-kappaB activity due to
      mutated NOD2. However, when attention was focused on the 2 most frequent
      mutations, R334W and R334Q, R334W tended to cause more obvious visual impairment.
      CONCLUSION: NOD2 genotyping may help predict disease progression in patients with
      Blau syndrome/EOS.

PMID- 19116922
TI  - CXCR3+CD4+ T cells are enriched in inflamed kidneys and urine and provide a new
      biomarker for acute nephritis flares in systemic lupus erythematosus patients.
AB  - OBJECTIVE: The high frequency of CD4+ T cells in interstitial infiltrates of
      patients with lupus nephritis suggests a contribution of these cells to local
      pathogenesis. The aim of this study was to examine the role of CXCR3 and the
      chemokine CXCL10 in recruiting these cells into the kidney and to determine
      whether the infiltrating T cells could be monitored in the urine to provide a
      reliable biomarker for acute lupus nephritis. METHODS: The frequencies of CD3+ T
      cells, CXCR3+ cells, and CXCL10+ cells were determined by immunohistochemical and
      immunofluorescence analyses of kidney sections from 18 patients with lupus
      nephritis. The frequency of CXCR3+CD4+ T cells was determined by flow cytometry
      of peripheral blood and urine from 38 patients with systemic lupus erythematosus
      (SLE), and the values were compared with disease activity as determined by the
      Systemic Lupus Erythematosus Disease Activity Index. RESULTS: In renal biopsy
      tissues from patients with lupus nephritis, a mean of 63% of the infiltrating
      cells expressed CXCR3, approximately 60% of them were T cells, and the CXCR3+
      cells colocalized with CXCL10-producing cells. In biopsy tissues from SLE
      patients with acute nephritis, approximately 50% of the urinary CD4+ T cells were
      CXCR3+, as compared with 22% in the peripheral blood, and the frequency of
      urinary CXCR3+CD4+ T cells correlated with disease activity. Moreover, the number
      of urinary CD4+ T cells reflected nephritis activity, and elevation above 800
      CD4+ T cells per 100 ml of urine sharply delineated active from inactive
      nephritis. CONCLUSION: CXCR3+ T cells are recruited into the inflamed kidneys,
      are enriched in the urine, and are a valuable marker of nephritis activity in
      SLE. They also present a potential target for future therapies.

PMID- 19116921
TI  - Different patterns of associations with anti-citrullinated protein antibody
      positive and anti-citrullinated protein antibody-negative rheumatoid arthritis in
      the extended major histocompatibility complex region.
AB  - OBJECTIVE: To identify additional variants in the major histocompatibility
      complex (MHC) region that independently contribute to risk in 2 disease subsets
      of rheumatoid arthritis (RA) defined according to the presence or absence of
      antibodies to citrullinated protein antigens (ACPAs). METHODS: In a multistep
      analytical strategy using unmatched as well as matched analyses to adjust for HLA
      DRB1 genotype, we analyzed 2,221 single-nucleotide polymorphisms (SNPs) spanning
      10.7 Mb, from 6p22.2 to 6p21.31, across the MHC. For ACPA-positive RA, we
      analyzed samples from the Swedish Epidemiological Investigation of Rheumatoid
      Arthritis (EIRA) and the North American Rheumatoid Arthritis Consortium (NARAC)
      studies (totaling 1,255 cases and 1,719 controls). For ACPA-negative RA, we used
      samples from the EIRA study (640 cases and 670 controls). Plink and SAS
      statistical packages were used to conduct all statistical analyses. RESULTS: A
      total of 299 SNPs reached locus-wide significance (P<2.3x10(-5)) for ACPA
      positive RA, whereas surprisingly, no SNPs reached this significance for ACPA
      negative RA. For ACPA-positive RA, we adjusted for known DRB1 risk alleles and
      identified additional independent associations with SNPs near HLA-DPB1
      (rs3117213; odds ratio 1.42 [95% confidence interval 1.17-1.73], Pcombined=0.0003
      for the strongest association). CONCLUSION: There are distinct genetic patterns
      of MHC associations in the 2 disease subsets of RA defined according to ACPA
      status. HLA-DPB1 is an independent risk locus for ACPA-positive RA. We did not
      identify any associations with SNPs within the MHC for ACPA-negative RA.

PMID- 19116923
TI  - Genetic association of the major histocompatibility complex with rheumatoid
      arthritis implicates two non-DRB1 loci.
AB  - OBJECTIVE: The HLA-DRB1 locus within the major histocompatibility complex (MHC)
      at 6p21.3 has been identified as a susceptibility gene for rheumatoid arthritis
      (RA); however, there is increasing evidence of additional susceptibility genes in
      the MHC region. The aim of this study was to estimate their number and location.
      METHODS: A case-control study was performed involving 977 control subjects and
      855 RA patients. The HLA-DRB1 locus was genotyped together with 2,360 single
      nucleotide polymorphisms in the MHC region. Logistic regression was used to
      detect DRB1-independent effects. RESULTS: After adjusting for the effect of HLA
      DRB1, 18 markers in 14 genes were strongly associated with RA (P<10(-4)).
      Multivariate logistic regression analysis of these markers and DRB1 led to a
      model containing DRB1 plus the following 3 markers: rs4678, a nonsynonymous
      change in the VARS2L locus, approximately 1.7 Mb telomeric of DRB1; rs2442728,
      upstream of HLA-B, approximately 1.2 Mb telomeric of DRB1; and rs17499655,
      located in the 5'-untranslated region of DQA2, only 0.1 Mb centromeric of DRB1.
      In-depth investigation of the DQA2 association, however, suggested that it arose
      through cryptic linkage disequilibrium with an allele of DRB1. Two non-shared
      epitope alleles were also strongly associated with RA (P<10(-4)): *0301 with anti
      cyclic citrullinated peptide-negative RA and *0701 independently of autoantibody
      status. CONCLUSION: These results confirm the polygenic contribution of the MHC
      to RA and implicate 2 additional non-DRB1 susceptibility loci. The role of the
      HLA-DQ locus in RA has been a subject of controversy, but in our data, it appears
      to be spurious.

PMID- 19116925
TI  - Clinical images: Hypertension due to otherwise asymptomatic, complete aortic
      occlusion in Takayasu arteritis.

PMID- 19116924
TI  - Tolerization with Hsp65 induces protection against adjuvant-induced arthritis by
      modulating the antigen-directed interferon-gamma, interleukin-17, and antibody
      responses.
AB  - OBJECTIVE: Pretreatment of Lewis rats with soluble mycobacterial Hsp65 affords
      protection against subsequent adjuvant-induced arthritis (AIA). This study was
      aimed at unraveling the mechanisms underlying mycobacterial Hsp65-induced
      protection against arthritis, using contemporary parameters of immunity. METHODS:
      Lewis rats were given 3 intraperitoneal injections of mycobacterial Hsp65 in
      solution prior to the initiation of AIA with heat-killed Mycobacterium
      tuberculosis. Thereafter, mycobacterial Hsp65-specific T cell proliferative,
      cytokine, and antibody responses were tested in tolerized rats. The roles of
      anergy and the indoleamine 2,3 dioxygenase (IDO)-tryptophan pathway in tolerance
      induction were assessed, and the frequency and suppressive function of CD4+FoxP3+
      Treg cells were monitored. Also tested was the effect of mycobacterial Hsp65
      tolerization on T cell responses to AIA-related mycobacterial Hsp70,
      mycobacterial Hsp10, and rat Hsp65. RESULTS: The AIA-protective effect of
      mycobacterial Hsp65-induced tolerance was associated with a significantly reduced
      T cell proliferative response to mycobacterial Hsp65, which was reversed by
      interleukin-2 (IL-2), indicating anergy induction. The production of interferon
      gamma (but not IL-4/IL-10) was increased, with concurrent down-regulation of IL
      17 expression by mycobacterial Hsp65-primed T cells. Neither the frequency nor
      the suppressive activity of CD4+FoxP3+ T cells changed following tolerization,
      but the serum level of anti-mycobacterial Hsp65 antibodies was increased.
      However, no evidence was observed for a role of IDO or cross-tolerance to
      mycobacterial Hsp70, mycobacterial Hsp10, or rat Hsp65. CONCLUSION: Tolerization
      with soluble mycobacterial Hsp65 leads to suppression of IL-17, anergy induction,
      and enhanced production of anti-mycobacterial Hsp65 antibodies, which play a role
      in protection against AIA. These results are relevant to the development of
      effective immunotherapeutic approaches for autoimmune arthritis.

PMID- 19116926
TI  - Thymic function and immune senescence in juvenile idiopathic arthritis: comment
      on the article by Prelog et al.

PMID- 19116932
TI  - Activation of synoviolin promoter in rheumatoid synovial cells by a novel
      transcription complex of interleukin enhancer binding factor 3 and GA binding
      protein alpha.
AB  - OBJECTIVE: Synoviolin is an E3 ubiquitin ligase, and its overexpression is
      implicated in the pathogenesis of rheumatoid arthritis (RA). We reported
      previously that Ets binding site 1 (EBS-1) within the synoviolin promoter is
      crucial for the expression of synoviolin, and GA binding protein (GABP) binds to
      this site. This study was undertaken to elucidate the precise mechanisms of
      transcriptional regulation via EBS-1. METHODS: We performed purification and
      identification of complex components that bind to EBS-1 and inspected their
      contributions to the transcriptional regulation of synoviolin in rheumatoid
      synovial cells. We biochemically purified proteins that had EBS-1 binding
      activity and identified the proteins using liquid chromatography tandem mass
      spectrometry analysis. The identified proteins were verified to recruit and form
      the complex on EBS-1 using electrophoretic mobility shift assay and
      coimmunoprecipitation assay. Furthermore, their transcription activities were
      tested by reporter assays and RNA interference experiments. RESULTS: We
      identified interleukin enhancer binding factor 3 (ILF-3) as a novel factor in the
      complex. ILF-3 was demonstrated to activate the synoviolin promoter via
      association with GABPalpha in rheumatoid synovial cells. In addition, further
      activation was observed with ILF-2 and GABPbeta, previously reported interactants
      of ILF-3 and GABPalpha, respectively. Moreover, ILF-3-knockdown experiments
      showed reduced expression of the synoviolin gene. CONCLUSION: Our findings
      indicate that ILF-3, which has been known to regulate IL-2 expression in T cells,
      up-regulates synoviolin expression with GABPalpha in rheumatoid synovial cells.
      ILF-3 might be a target for RA treatment through its effect on IL-2 in T cells
      and synoviolin in rheumatoid synovial cells.

PMID- 19116933
TI  - Identification of a novel susceptibility locus for juvenile idiopathic arthritis
      by genome-wide association analysis.
AB  - OBJECTIVE: Juvenile idiopathic arthritis (JIA) is a chronic rheumatic disease of
      childhood. Two well-established genetic factors known to contribute to JIA
      susceptibility, HLA and PTPN22, account for less than half of the genetic
      susceptibility to disease; therefore, additional genetic factors have yet to be
      identified. The purpose of this study was to perform a systematic search of the
      genome to identify novel susceptibility loci for JIA. METHODS: A genome-wide
      association study using Affymetrix GeneChip 100K arrays was performed in a
      discovery cohort (279 cases and 184 controls). Single-nucleotide polymorphisms
      (SNPs) showing the most significant differences between cases and controls were
      then genotyped in a validation sample of cases (n = 321) and controls, combined
      with control data from the 1958 UK birth cohort (n = 2,024). In one region in
      which association was confirmed, fine-mapping was performed (654 cases and 1,847
      controls). RESULTS: Of the 112 SNPs that were significantly associated with JIA
      in the discovery cohort, 6 SNPs were associated with JIA in the independent
      validation cohort. The most strongly associated SNP mapped to the HLA region,
      while the second strongest association was with a SNP within the VTCN1 gene. Fine
      mapping of that gene was performed, and 10 SNPs were found to be associated with
      JIA. CONCLUSION: This study is the first to successfully apply a SNP-based genome
      wide association approach to the investigation of JIA. The replicated association
      with markers in the VTCN1 gene defined an additional susceptibility locus for JIA
      and implicates a novel pathway in the pathogenesis of this chronic disease of
      childhood.

PMID- 19116934
TI  - The chromosome 7q region association with rheumatoid arthritis in females in a
      British population is not replicated in a North American case-control series.
AB  - OBJECTIVE: The single-nucleotide polymorphism (SNP) rs11761231 on chromosome 7q
      has been reported to be sexually dimorphic marker for rheumatoid arthritis (RA)
      susceptibility in a British population. We sought to replicate this finding and
      to better characterize susceptibility alleles in the region in a North American
      population. METHODS: DNA from 2 North American collections of RA patients and
      controls (1,605 cases and 2,640 controls) was genotyped for rs11761231 and 16
      additional chromosome 7q tag SNPs using Sequenom iPlex assays. Association tests
      were performed for each collection and also separately, contrasting male cases
      with male controls and female cases with female controls. Principal components
      analysis (EigenStrat) was used to determine association with RA before and after
      adjusting for population stratification in the subset of the samples for which
      there were whole-genome SNP data (772 cases and 1,213 controls). RESULTS: We
      failed to replicate an association of the 7q region with RA. Initially,
      rs11761231 showed evidence for association with RA in the North American
      Rheumatoid Arthritis Consortium (NARAC) collection (P=0.0073), and rs11765576
      showed association with RA in both the NARAC (P=0.038) and RA replication (P =
      0.0013) collections. These markers also exhibited sex differentiation. However,
      in the whole-genome subset, neither SNP showed significant association with RA
      after correction for population stratification. CONCLUSION: While 2 SNPs on
      chromosome 7q appeared to be associated with RA in a North American cohort, the
      significance of this finding did not withstand correction for population
      substructure. Our results emphasize the need to carefully account for population
      structure to avoid false-positive disease associations.

PMID- 19116935
TI  - CTLA-4 (CD152) controls homeostasis and suppressive capacity of regulatory T
      cells in mice.
AB  - OBJECTIVE: CD4+CD25+ regulatory T cells (known as Treg cells) suppress unwanted
      and autoreactive T cell responses. Treg cells express the costimulatory molecule
      CTLA-4 intracellularly, but the mechanisms by which Treg cells exploit CTLA-4
      signaling remain unclear. The present study was undertaken to investigate the
      role of CTLA-4 in controlling the homeostasis and suppressive function of Treg
      cells. METHODS: Murine Treg cells were analyzed by flow cytometry for
      coexpression of CTLA-4 and typical Treg cell-expressed molecules, and the
      influence of CTLA-4 on T cell proliferation, suppression, and apoptosis was
      investigated by in vitro assays. To analyze the importance of CTLA-4 in Treg cell
      mediated suppression in vivo, wild-type Treg cells were transferred into CTLA-4
      deficient mice displaying lymphoproliferation, and survival was monitored over
      time. RESULTS: A strong correlation between expression of forkhead box P3 and ex
      vivo expression of CTLA-4 in Treg cells was observed. Inhibition of CTLA-4
      signaling in Treg cells during in vitro stimulation increased cell cycling and
      led to enhanced activation-induced cell death (AICD), which was mediated by
      CD95/CD95 ligand-induced activation of caspases. Blockade of CTLA-4 signaling
      resulted in impairment of the suppressive capacity of Treg cells. Despite these
      effects, high amounts of Treg cells persisted in CTLA-4-deficient mice. Results
      of transfer experiments in CTLA-4-deficient mice showed that the mice had a
      significantly prolonged lifespan when CTLA-4-competent Treg cells were injected.
      CONCLUSION: Expression of CTLA-4 on Treg cells serves to control T cell
      proliferation, to confer resistance against AICD, and to maintain the suppressive
      function of Treg cells.

PMID- 19116937
TI  - Association between the IRF5 rs2004640 functional polymorphism and systemic
      sclerosis: a new perspective for pulmonary fibrosis.
AB  - OBJECTIVE: There is now growing evidence that connective tissue diseases,
      including systemic sclerosis (SSc), share a common genetic background. Microarray
      studies support a pivotal role of type I interferon (IFN) in the pathophysiology
      of connective tissue diseases. Interferon regulatory factors coordinate the
      expression of type I IFNs, and the IRF5 gene has been identified as a
      susceptibility gene of systemic lupus and Sjogren's syndrome. The aim of this
      study was to determine whether the IRF5 rs2004640 single-nucleotide polymorphism
      is associated with SSc. METHODS: The IRF5 rs2004640 (GT) functional polymorphism
      was genotyped in 1,641 subjects of French European Caucasian origin: a discovery
      set comprising 427 patients with SSc and 380 control subjects and a replication
      set comprising 454 patients with SSc and 380 control subjects. RESULTS: In both
      the discovery set and the replication set, the TT genotype was significantly more
      common in patients with SSc than in control subjects, with an odds ratio (OR) for
      the combined populations of 1.58 (95% confidence interval [95% CI] 1.18-2.11 [P
      for trend 0.002]). Analyses of the whole SSc population showed a significant
      association between homozygosity for the T allele and the presence of antinuclear
      antibodies (corrected P [Pcorr]=0.04, OR 1.59, 95% CI 1.16-2.17) and fibrosing
      alveolitis (Pcorr=0.001, OR 2.07, 95% CI 1.38-3.11). In a multivariate analysis
      model including the diffuse cutaneous subtype of SSc and positivity for anti
      topoisomerase I antibodies, the IRF5 rs2004640 TT genotype remained associated
      with fibrosing alveolitis (P=0.029, OR 1.92, 95% CI 1.07-3.44). CONCLUSION: The
      IRF5 rs2004640 GT substitution is associated with susceptibility to SSc. These
      data provide new insight into the pathogenesis of SSc, including clues to the
      mechanisms leading to fibrosing alveolitis.

PMID- 19116936
TI  - Quadriceps strength and the risk of cartilage loss and symptom progression in
      knee osteoarthritis.
AB  - OBJECTIVE: To determine the effect of quadriceps strength in individuals with
      knee osteoarthritis (OA) on loss of cartilage at the tibiofemoral and
      patellofemoral joints (assessed by magnetic resonance imaging [MRI]) and on knee
      pain and function. METHODS: We studied 265 subjects (154 men and 111 women,
      mean+/-SD age 67+/-9 years) who met the American College of Rheumatology criteria
      for symptomatic knee OA and who were participating in a prospective, 30-month
      natural history study of knee OA. Quadriceps strength was measured at baseline,
      isokinetically, during concentric knee extension. MRI of the knee at baseline and
      at 15 and 30 months was used to assess cartilage loss at the tibiofemoral and
      patellofemoral joints, with medial and lateral compartments assessed separately.
      At baseline and at followup visits, knee pain was assessed using a visual analog
      scale, and physical function was assessed using the Western Ontario and McMaster
      Universities Osteoarthritis Index. RESULTS: There was no association between
      quadriceps strength and cartilage loss at the tibiofemoral joint. Results were
      similar in malaligned knees. However, greater quadriceps strength was protective
      against cartilage loss at the lateral compartment of the patellofemoral joint
      (for highest versus lowest tertile of strength, odds ratio 0.4 [95% confidence
      interval 0.2, 0.9]). Those with greater quadriceps strength had less knee pain
      and better physical function over followup (P<0.001). CONCLUSION: Greater
      quadriceps strength had no influence on cartilage loss at the tibiofemoral joint,
      including in malaligned knees. We report for the first time that greater
      quadriceps strength protected against cartilage loss at the lateral compartment
      of the patellofemoral joint, a finding that requires confirmation. Subjects with
      greater quadriceps strength also had less knee pain and better physical function
      over followup.

PMID- 19116938
TI  - The combination of the biomarkers urinary C-terminal telopeptide of type II
      collagen, serum cartilage oligomeric matrix protein, and serum chondroitin
      sulfate 846 reflects cartilage damage in hemophilic arthropathy.
AB  - OBJECTIVE: Hemophilic arthropathy, with characteristics of inflammatory
      (rheumatoid arthritis) and degenerative (osteoarthritis) joint damage, occurs at
      an early age, is associated with minor comorbidity, and is restricted to 3 pairs
      of large joints. The aim of this study was to determine whether commonly used
      serum and/or urinary biomarkers of cartilage and bone turnover for which assay
      kits are commercially available are associated with the severity of joint damage
      in patients with various degrees of hemophilic arthropathy and, thus, whether
      this disease could be useful in the identification and evaluation of such
      biomarkers. METHODS: Blood and urine samples were collected from 36 patients with
      various degrees of hemophilic arthropathy. Commercially available assays for the
      most frequently investigated serum and urine biomarkers were performed: urinary C
      terminal telopeptide of type I collagen (CTX-I), urinary CTX-II, serum CTX-I,
      serum CTX-II, serum cartilage oligomeric matrix protein (COMP), serum cartilage
      cleavage products C1,2C and C2C, and serum chondroitin sulfate 846 (CS-846).
      Radiographs of the ankles, knees, and elbows in all patients were evaluated for
      the degree of joint damage according to the Pettersson score, which is based on
      cartilage and periarticular bone changes and is specific for hemophilic
      arthropathy. RESULTS: Urinary CTX-II, serum C1,2C, and serum CS-846 levels
      correlated with the overall Pettersson score and with the joint space narrowing
      component. Regression analysis showed that combined indexes of different markers
      increased the degree of correlation for the combination of urinary CTX-II, serum
      COMP, and serum CS-846. Bone-specific markers (urinary/serum CTX-I and serum
      C1,2C) did not correlate with specific bone-related items of the Pettersson score
      (osteoporosis and erosions). CONCLUSION: These results support the idea that a
      combination of biomarkers relates significantly better to the severity of joint
      damage than do individual biomarkers. The combination of urinary CTX-II, serum
      COMP, and serum CS-846 correlated best with the degree of arthropathy. Because of
      its specific characteristics and restricted involvement, hemophilic arthropathy
      may prove useful in the screening of newly developed biomarkers of joint damage.

PMID- 19116939
TI  - Resident macrophages initiating and driving inflammation in a monosodium urate
      monohydrate crystal-induced murine peritoneal model of acute gout.
AB  - OBJECTIVE: To determine whether infiltrating monocytes, neutrophils, or resident
      macrophages contribute to the early inflammatory response to monosodium urate
      monohydrate (MSU) crystals in vivo. METHODS: MSU crystal-induced inflammation was
      monitored using a peritoneal model of acute gout. The production of
      proinflammatory cytokines (interleukin-1beta [IL-1beta], tumor necrosis factor
      alpha [TNFalpha], IL-6) by resident macrophages, infiltrating monocytes, and
      neutrophils during the onset of gout was determined by flow cytometry.
      Infiltrating and resident peritoneal cells were cultured with MSU crystals ex
      vivo, and proinflammatory cytokine production was determined by multiplex
      cytokine array. Activated macrophages on the visceral epithelial lining of the
      peritoneum were identified by immunofluorescence histochemistry. The inflammatory
      immune response to MSU crystals was then compared with the inflammatory response
      in mice depleted of resident macrophages by pretreatment with clodronate
      liposomes. RESULTS: The production of cytokines in vivo preceded the influx of Gr
      1(intermediate)7/4+ monocytes. Monocytes and neutrophils recruited during the
      inflammatory phase of the response to MSU crystals failed to produce
      proinflammatory cytokines either in vivo, or ex vivo following restimulation with
      MSU crystals. Stimulation of the naive peritoneal resident cell population with
      MSU crystals ex vivo resulted in positive staining of resident macrophages for
      the proinflammatory cytokines IL-1beta, TNFalpha, and IL-6. Depletion of the
      resident macrophage population resulted in a significant decrease in both MSU
      crystal-induced neutrophil infiltration and proinflammatory cytokine production
      in vivo despite the presence of infiltrating monocytes. CONCLUSION: These data
      indicate that resident macrophages, rather than infiltrating monocytes or
      neutrophils, are important for initiating and driving the early proinflammatory
      phase of acute gout.

PMID- 19116940
TI  - Treatment with imatinib prevents fibrosis in different preclinical models of
      systemic sclerosis and induces regression of established fibrosis.
AB  - OBJECTIVE: Imatinib is a small-molecule tyrosine kinase inhibitor capable of
      selective, dual inhibition of the transforming growth factor beta and platelet
      derived growth factor (PDGF) pathways. Imatinib has previously been shown to
      prevent the development of inflammation-driven experimental fibrosis when
      treatment was initiated before administration of the profibrotic stimulus. The
      aim of this study was to confirm the efficacy of imatinib in a murine model of
      systemic sclerosis (SSc) that is less driven by inflammation and to investigate
      whether imatinib is also effective for the treatment of established fibrosis.
      METHODS: The tight skin 1 (TSK-1) mouse model of SSc was used to evaluate the
      antifibrotic effects of imatinib in a genetic model of the later stages of SSc.
      In addition, the efficacy of imatinib for the treatment of preestablished
      fibrosis was analyzed in a modified model of bleomycin-induced dermal fibrosis in
      which the application of bleomycin was prolonged and the onset of treatment was
      late. RESULTS: Treatment with imatinib reduced dermal and hypodermal thickening
      in TSK-1 mice and prevented the differentiation of resting fibroblasts into
      myofibroblasts. In the model of preestablished dermal fibrosis, imatinib not only
      stopped further progression of fibrosis but also induced regression of
      preexisting dermal fibrosis, with a reduction in dermal thickness below
      pretreatment levels. CONCLUSION: These results indicate that combined inhibition
      of the tyrosine kinase c-Abl and PDGF receptor might be effective in the later,
      less inflammatory stages of SSc and for the treatment of established fibrosis.
      Thus, imatinib might be an interesting candidate for clinical trials in patients
      with longstanding disease and preexisting tissue fibrosis.

PMID- 19116941
TI  - Association between C-reactive protein and pre-diabetic status in a Chinese Han
      clinical population.
AB  - BACKGROUND: C-reactive protein (CRP) has been showed to be associated with type 2
      diabetes mellitus, but whether CRP underlies glucose disorders in Asian people is
      still unclear, for they have much lower body mass index (BMI) levels than these
      Westerns in previous studies. METHOD: In this clinical-based cross-sectional
      study, the association between CRP and hyperglycaemia in different BMI levels and
      different gender was compared among 1730 Chinese Han men and women, including
      1258 subjects with normal glucose tolerance (NGT), 126 subjects with impaired
      fasting glucose (IFG) and 346 subjects with impaired glucose tolerance (IGT).
      Subjects with isolated IFG or IGT were all newly diagnosed and did not use anti
      diabetic drugs. RESULTS: Compared with subjects with NGT, BMI, fasting blood
      glucose, homoeostasis model assessment insulin resistance (HOMA-IR), blood
      pressure, dyslipidemia, and serum CRP levels were increased in subjects with IGT
      and IFG. In stratified analyses, increasing CRP levels were strongly associated
      with prevalence of IGT and IFG in different BMI strata. After adjustment for sex,
      age, BMI, education, alcohol consumption, smoking, hypertension status,
      recreational physical activity and occupational physical activity, the ORs across
      quartiles of CRP were 1.00, 1.43, 2.14 and 2.29 for IFG (P for trend: 0.025) and
      1.00, 1.85, 2.32 and 2.79 for IGT (P for trend: 0.012). CONCLUSION: These results
      support the hypothesis that chronic inflammation may be involved in the
      development of hyperglycaemia, even though in a thinner and healthy population.

PMID- 19116942
TI  - Early insulin secretion failure leads to diabetes in Chinese subjects with
      impaired glucose regulation.
AB  - BACKGROUND: Both beta-cell dysfunction and decreased insulin sensitivity are
      involved in the pathogenesis of impaired glucose tolerance (IGT) and impaired
      fasting glucose (IFG), while their relative contribution in the progression to
      type 2 diabetes still remains controversial. The aim of the present study is to
      clarify this process in Chinese subjects by using cross-sectional method.
      METHODS: 2,975 Chinese subjects were classified into: normal glucose tolerance
      (NGT), impaired glucose regulations (IGR), and diabetes mellitus (DM) based on
      oral glucose tolerance test (OGTT). The IGR group was sub-classified as isolated
      IFG, isolated IGT and combined glucose intolerance (CGI). The DM group was sub
      classified as normal fasting plasma glucose and 2-hour hyperglycemia (N0D2),
      fasting hyperglycemia and normal 2-hour plasma glucose (D0N2), and both fasting
      and 2-hour hyperglycemia (D0D2). RESULTS: As far as insulinogenic index (IGI) was
      concerned, there was no difference between IFG and IGT in either gender, however,
      HOMA2-B% (homeostasis model assessment for beta-cell function) of IGT was higher
      than that of IFG and CGI in both male and female (P < 0.05). In the diabetic sub
      groups, IGI of N0D2 was higher than that of D0N2, and both deteriorated compared
      with those of IGT and IFG, respectively. HOMA2-B% of N0D2 was still higher than
      that of D0N2 and D0D2. No significant difference was detected in OGIS and HOMA2
      S% (homeostasis model assessment for insulin sensitivity) between IFG and IGT,
      and this was the case between N0D2 and D0N2. OGIS and HOMA-IR of IGR sub-groups
      were not different from those of their diabetic counterparts. CONCLUSION: Failure
      of beta-cell function might be the main reason for both IGT and IFG developing
      into diabetes instead of aggravated insulin resistance.

PMID- 19116944
TI  - Structural characterization of flavonoid glycosides by multi-stage mass
      spectrometry.
AB  - Flavonoids are secondary plant metabolites of great structural variety and high
      medicinal significance. The search for new chemical entities and the quality
      control of flavonoid containing natural products require easy-to-use but reliable
      and robust analytical methodologies. For structural elucidation of flavonoids and
      their glycosides, nuclear magnetic resonance (NMR) and mass spectroscopy (MS) are
      the generally used techniques. In phytochemical analyses, however, high amounts
      of flavonoids are difficult to isolate for NMR, thus low sample volume requiring
      MS based methods are emerging. This review summarizes and compares currently
      available methods for structural elucidation of flavonoids by LC-MS and LC-MS(n),
      and focuses on the identification options of unknown flavonoid glycosides in
      complex samples (e.g., plant extracts) with the emphasis on the differentiation
      of isomeric compounds.

PMID- 19116943
TI  - Acute effects of sildenafil on flow mediated dilatation and cardiovascular
      autonomic nerve function in type 2 diabetic patients.
AB  - BACKGROUND: Sildenafil, frequently used as on demand medication for the treatment
      of erectile dysfunction (ED), has been suggested to improve endothelial function
      but also to alter blood pressure (BP) and induce sympathetic activation. In
      people with type 2 diabetes mellitus (T2DM), a high-risk population, the safety
      profile and the effects on endothelial function of a maximal sildenafil dose (100
      mg) have not been investigated and therefore constituted the aim of our study.
      METHODS: A double-blind, placebo-controlled, cross-over trial using a single dose
      of 100 mg sildenafil or placebo has been conducted in 40 subjects with T2DM
      without known CVD. Haemodynamic parameters, flow mediated dilatation (FMD) in
      brachial artery, cardiovascular autonomic function tests and spontaneous
      baroreflex sensitivity (BRS) were measured. RESULTS: Sixty minutes after
      administration of sildenafil but not placebo, a fall of supine systolic blood
      pressure (SBP) (-5.41 +/- 1.87 vs. + 0.54 +/- 1.71 mmHg) and diastolic blood
      pressure (DBP) (-4.46 +/- 1.13 vs. + 0.89 +/- 0.94 mmHg), as well as orthostatic
      SBP (-7.41 +/- 2.35 vs. + 0.94 +/- 2.06 mmHg) and DBP (-5.65 +/- 1.45 vs. + 1.76
      +/- 1.00 mmHg) during standing occurred, accompanied by an increase in heart rate
      (+1.98 +/- 0.69 vs. - 2.42 +/- 0.59 beats/min) (all p < 0.01 vs. placebo).
      Changes in BP to standing up, FMD, time domain and frequency domain indices of
      heart rate variability (HRV) and BRS were comparable between sildenafil and
      placebo. CONCLUSIONS: Sildenafil administered at a maximum single dose to T2DM
      men results in a mild increase in heart rate and decrease in BP, but it induces
      neither an acute improvement of FMD nor any adverse effects on orthostatic BP
      regulation, HRV and BRS.

PMID- 19116945
TI  - Biophysical characterization and formulation of F1-V, a recombinant plague
      antigen.
AB  - The recombinant plague antigen, F1-V, was studied for its structural
      characteristics using several biophysical techniques. A larger apparent molecular
      weight relative to its calculated molecular weight obtained from size exclusion
      chromatography, an unusually large R(g) obtained from MALS, and ANS dye binding
      studies which indicate that all hydrophobic regions of the protein are exposed to
      solvent demonstrated that F1-V exists like a disordered protein with a worm-like
      conformation. The pH-solubility profile of F1-V showed a solubility minimum at pH
      5, close to its pI, consistent with the lack of repulsive forces that result in
      aggregation. Thus, in contrast to most globular proteins that exhibit a secondary
      and a tertiary structure, F1-V seems to lack tertiary structure and like an
      unfolded protein is more prone to aggregation via hydrophobic interactions.
      Despite this, when renatured gradually using descending guanidine hydrochloride
      concentration dialysis, in the presence of Mg+2, a surfactant and arginine
      hydrochloride at a pH of 7.5, F1-V appears to populate predominantly in its
      monomeric state.

PMID- 19116946
TI  - Proteomics of brain extracellular fluid (ECF) and cerebrospinal fluid (CSF).
AB  - Mass spectrometry has become the gold standard for the identification of proteins
      in proteomics. In this review, I will discuss the available literature on
      proteomic experiments that analyze human cerebrospinal fluid (CSF) and brain
      extracellular fluid (ECF), mostly obtained by cerebral microdialysis. Both
      materials are of high diagnostic value in clinical neurology, for example, in
      cerebrovascular disorders like stroke, neurodegenerative diseases like
      Alzheimer's Disease, Parkinson's Disease, amyotrophic lateral sclerosis (ALS),
      traumatic brain injury and cerebral infectious and inflammatory disease, such as
      multiple sclerosis. Moreover, there are standard procedures for sampling. In a
      number of studies in recent years, biomarkers have been proposed in CSF and ECF
      for improved diagnosis or to control therapy, based on proteomics and mass
      spectrometry. I will also discuss the needs for a transition of research-based
      experimental screening with mass spectrometry to fast and reliable diagnostic
      instrumentation for clinical use.

PMID- 19116947
TI  - Differential regulation of prodynophin, c-fos, and serotonin transporter mRNA
      following withdrawal from a chronic, escalating dose regimen of D-amphetamine.
AB  - Several lines of evidence suggest that D-amphetamine (D-AMPH) withdrawal induces
      a syndrome with symptoms similar to major depressive disorder (MDD). Upregulation
      of dynorphin (DYN) may underlie the symptoms of MDD and contribute to the
      negative emotional symptoms associated with psychostimulant withdrawal. Changes
      in the serotonin transporter (SERT) have also been reported in MDD, and changes
      in the immediate early gene c-fos have been observed in the context of
      psychostimulant withdrawal. This study examined the effects of chronic,
      escalating doses of D-AMPH followed by 24 h of withdrawal on the expression of
      prodynorphin (PD) and c-fos mRNA in limbic regions of the brain, caudate putamen
      (CPu), and brainstem and SERT mRNA expression in the dorsal raphe nucleus (DRN).
      Male Sprague-Dawley rats were treated three times a day for 4 days with
      escalating doses of D-AMPH (1-10 mg/kg) and sacrificed 24 h after the last
      injection. Following 24 h of withdrawal, there was an increase in PD and c-fos
      mRNA expression in the CPu and nucleus accumbens (NAc), and a decrease in PD and
      c-fos expression in hippocampus and amygdala. SERT mRNA expression was decreased
      in the DRN, and PD mRNA expression was increased in the adjacent ventrolateral
      periaqueductal gray (VLPAG) following D-AMPH withdrawal. These data indicate that
      region-specific changes in PD and c-fos expression occur after withdrawal, while
      SERT mRNA expression is suppressed, similar to what has been reported in MDD.
      Alterations in PD, c-fos, and SERT expression could contribute to the depression
      like syndrome associated with psychostimulant withdrawal.

PMID- 19116948
TI  - Presynaptic and postsynaptic modulation of glutamatergic synaptic transmission by
      activation of alpha(1)- and beta-adrenoceptors in layer V pyramidal neurons of
      rat cerebral cortex.
AB  - Adrenergic agonists have different modulatory effects on excitatory synaptic
      transmission depending on the receptor subtypes involved. The present study
      examined the loci of alpha(1)- and beta-adrenoceptor agonists, which have
      opposite effects on excitatory neural transmission, involved in modulation of
      glutamatergic transmission in layer V pyramidal cells of rat cerebral cortex.
      Phenylephrine, an alpha(1)-adrenoceptor agonist, suppressed the amplitude of AMPA
      receptor-mediated excitatory postsynaptic currents evoked by repetitive
      electrical stimulation (eEPSCs, 10 pulses at 33 Hz). The coefficient of variation
      (CV) of the 1st eEPSC amplitude and paired-pulse ratio (PPR), which were
      sensitive to extracellular Ca(2+) concentration, were not affected by
      phenylephrine. Phenylephrine suppressed miniature EPSC (mEPSC) amplitude without
      changing its frequency. In contrast, isoproterenol, a beta-adrenoceptor agonist,
      strongly increased the amplitude of the 1st eEPSC compared with that of the 2nd
      to 10th eEPSCs, which resulted in a decrease in PPR. Isoproterenol-induced
      enhancement of eEPSC amplitude was accompanied by a decrease in CV. Isoproterenol
      increased the frequency of mEPSCs without significant effect on amplitude.
      Phenylephrine suppressed inward currents evoked by puff application of glutamate,
      AMPA, or NMDA, whereas isoproterenol application was not accompanied by
      significant changes in these inward currents. These findings suggest that
      phenylephrine decreases eEPSCs through postsynaptic AMPA or NMDA receptors, while
      the effects of isoproterenol are mediated by facilitation of glutamate release
      from presynaptic terminals without effect on postsynaptic glutamate receptors.
      These two different mechanisms of modulation of excitatory synaptic transmission
      may improve the "signal-to-noise ratio" in cerebral cortex.

PMID- 19116949
TI  - Regional analysis of age-related decline in dopamine transporters and dopamine D2
      like receptors in human striatum.
AB  - The purpose of this study was to evaluate the mechanisms of age-related decline
      of dopamine transporter (DAT) and dopamine D(2)-like receptor (D2R) densities in
      the human striatum by focusing on regional difference. METHODS: Positron emission
      tomography (PET) with [(11)C]CFT and [(11)C]raclopride for measuring DATs and
      D2Rs, respectively, was performed on 16 healthy volunteers ranging from 21 to 74
      years in age. To evaluate in detail the regional difference within the striatum,
      in addition to the conventional region-of-interest-based analysis, we created a
      parametric image that enabled us to visualize the regional decline rate on a
      voxel-by-voxel basis, mapping the slope of the regression line between the age
      and uptake index of each tracer. RESULTS: The decreasing rates corresponded to
      6.1, 5.5, and 5.6% per decade for DATs and 5.8, 4.9, and 4.8% per decade for
      D(2)Rs in the caudate nucleus, anterior putamen, and posterior putamen,
      respectively. The caudate nucleus for both DATs and D(2)Rs were the fastest among
      the striatum, and the regional difference of the decreasing rate for DATs was
      consistently associated with that for D2Rs. Meanwhile, previous histological
      studies have shown that age-related cell loss in the substantia nigra is likely
      to preferentially affect its dorsomedial part, which projects to the caudate
      nucleus. CONCLUSIONS: These results suggested that neuronal cell loss in the
      substantia nigra may be associated with the age-related DAT decline, and DAT
      decline may be associated functionally with age-related D2R decline.

PMID- 19116950
TI  - Immunocytochemical localization of NTPDases1 and 2 in the neural retina of mouse
      and zebrafish.
AB  - Ectonucleoside triphosphate diphosphohydrolases (E-NTPDases) are a family of
      membrane-bound enzymes that hydrolyze extracellular di- and triphosphate
      nucleosides. E-NTPDases have been proposed to control extracellular nucleotide
      levels that mediate intercellular communication by binding to specific membrane
      receptors. Here we show a detailed immunocytochemical localization of two enzymes
      of the E-NTPDase family in the retinal layers of two vertebrate species, namely,
      the mouse and the zebrafish. In the mouse retina, NTPDase2 was chiefly localized
      in Muller glia and ganglion cell processes. NTPDase1 was located on neurons as
      well, since it was expressed by horizontal and ganglion cell processes,
      suggesting that nucleotides such as ATP and ADP can be hydrolyzed at the surface
      of these cells. NTPDase1 was also detected in intraretinal blood vessels of the
      mouse. Regarding zebrafish, NTPDases1 and 2 seem to be differentially localized
      in horizontal cell processes, photoreceptor segments, and ganglion cell dendrites
      and axons, but absent from Muller glia. Moreover, NTPDases1 and 2 appear to be
      expressed within the germinal margin of the zebrafish retina that contains
      proliferative and differentiating cells. Retinal homogenates from both species
      exhibited ecto-ATPase activity which might be attributed at least to NTPDases1
      and 2, whose expression is described in this report. Our results suggest a
      compartmentalized regulation of extracellular nucleotide/nucleoside concentration
      in the retinal layers, supporting a relevant role for extracellular nucleotide
      mediated-signaling in vertebrate retinas.

PMID- 19116952
TI  - Quality-by-design (QbD): an integrated approach for evaluation of powder blending
      process kinetics and determination of powder blending end-point.
AB  - The objective of this study was to develop an integrated process monitoring
      approach for evaluating powder blending process kinetics and determining blending
      process end-point. A mixture design was created to include 26 powder formulations
      consisting of ibuprofen as the model drug and three excipients (HPMC, MCC, and
      Eudragit L100-55). The mixer was stopped at various time points to enable near
      infrared spectroscopy scan of the powder mixture for obtaining the time course of
      the blending process. The evaluation of the blending process kinetics and process
      end-point was studied through three quantitative approaches: (1) Spectra linear
      superposition method; (2) Characteristic peak method; (3) Moving block standard
      deviation method. It was found that the powder blending experienced an initial
      rapid process to reach a quasi- end point within the first few minutes.
      Afterwards, a demixing occurred. Then, a real blending end-point was reached as
      characterized by an inflection point. ANOVA shows that the compositions of
      ibuprofen and MCC are the most statistically significant variables that impact
      the time required to reach the blending end-point. This highlighted the critical
      importance of developing quantitative chemometric approaches to extract critical
      process information and generate essential process knowledge to enable real-time
      release of the blending process.

PMID- 19116951
TI  - A detailed investigation of maternally inherited diabetes and deafness (MIDD)
      including clinical characteristics, C-peptide secretion, HLA-DR and -DQ status
      and autoantibody pattern.
AB  - BACKGROUND: This article presents a clinically characterization of the
      mitochondrial DNA mutation (A3243G) associated with maternally inherited diabetes
      and deafness (MIDD) syndrome in two families. METHODS: Six patients with MIDD and
      one mutation-positive relative with normal glucose tolerance (NGT) were examined.
      Fasting serum C-peptide was measured in all subjects and compared with controls
      having NGT (n = 14). C-peptide response to an intravenous glucose tolerance test
      (IVGTT) was investigated in the diabetic patients not treated with insulin (n =
      3) and in the mutation-positive healthy individual and compared with the
      controls. RESULTS: The A3243G heteroplasmy value varied between 5 and 30%. All
      A3243G carriers had HLA-DR1-DQ5 haplotype, and either the -DQ5 or the -DQ6
      allele. The fasting and the serum C-peptide levels at 120 min during the IVGTT
      did not differ between the A3243G carriers and the controls. A missing first
      phase and a decreased total C-peptide response was detected in the mutation
      positive diabetics compared with controls (p < 0.0001). The same abnormality was
      found in the A3243G carrier with NGT. Circulating islet cell antibody (ICA) was
      present in three patients with MIDD. Glutamic acid decarboxylase (GAD), tyrosine
      phosphatase-like protein IA-2 (IA-2) and mitochondrial antibodies were missing.
      The diagnosis of MIDD was delayed in each case. CONCLUSIONS: A missing first
      phase and a decreased total C-peptide response during an IVGTT was characteristic
      for the A3243G mutation. The fasting C-peptide level of the carriers did not
      differ from the controls. Circulating ICA was present in some patients, but GAD,
      IA-2 and mitochondrial antibodies were absent. All subjects had HLA-DR1-DQ5
      haplotype, and either -DQ5 or -DQ6 alleles.

PMID- 19116953
TI  - The development and validation of a computational model to predict rat liver
      microsomal clearance.
AB  - As the cost of discovering and developing new pharmaceutically relevant compounds
      continues to rise, it is increasingly important to select the right molecules to
      prosecute very early in drug discovery. The development of high throughput in
      vitro assays of hepatic metabolic clearance has allowed for vast quantities of
      data generation; however, these large screens are still costly and remain
      dependant on animal usage. To further expand the value of these screens and
      ultimately aid in animal usage reduction, we have developed an in silico model of
      rat liver microsomal (RLM) clearance. This model combines a large amount of rat
      clearance data (n = 27,697) generated at multiple Pfizer laboratories to
      represent the broadest possible chemistry space. The model predicts RLM stability
      (with 82% accuracy and a kappa value of 0.65 for test data set) based solely on
      chemical structural inputs, and provides a clear assessment of confidence in the
      prediction. The current in silico model should help accelerate the drug discovery
      process by using confidence-based stability-driven prioritization, and reduce
      cost by filtering out the most unstable/undesirable molecules. The model can also
      increase efficiency in the evaluation of chemical series by optimizing iterative
      testing and promoting rational drug design.

PMID- 19116954
TI  - Distribution of saquinavir, methadone, and buprenorphine in maternal brain,
      placenta, and fetus during two different gestational stages of pregnancy in mice.
AB  - Efflux transporters such as P-glycoprotein (P-gp) play a critical role in the
      maternal-to-fetal and blood-to-brain transfer of many drugs. Using a mouse model,
      the effects of gestational age on P-gp and MRP expression in the placenta and
      brain were evaluated. P-gp protein levels in the placenta and brain were greater
      at mid-gestation (gd 13) than late-gestation (gd 18). Likewise, brain MRP1 levels
      were greater at mid-gestation, whereas, placental levels were greater at late
      gestation. To evaluate these effects on drug disposition, concentrations of
      [(3)H]saquinavir, [(3)H]methadone, [(3)H]buprenorphine, and the paracellular
      marker, [(14)C]mannitol were measured in plasma, brain, placenta, and fetal
      samples after i.v. administrations to nonpregnant and pregnant mice. Following
      i.v. administration, [(3)H]saquinavir placenta-to-plasma and fetal-to-plasma
      ratios were significantly greater in late-gestation mice versus mid-gestation.
      Furthermore, late-gestation mice experienced significant increases in the
      [(3)H]saquinavir and [(3)H]methadone brain-to-plasma ratios 60 min after dosing
      relative to mid-gestation (p < 0.05). No significant differences were observed in
      these tissue-to-plasma ratios for buprenorphine or mannitol. Repeated dosing
      (three doses, once daily) decreased the differential uptake of [(3)H]saquinavir
      in brain but potentiated it in the fetus. These results suggest that differential
      expression of P-gp and possibly MRP1 contributes to the gestational-induced
      changes in brain and fetal uptake of saquinavir.

PMID- 19116955
TI  - Emergency department visits attributed to selected analgesics, United States,
      2004-2005.
AB  - PURPOSE: To estimate the rate of emergency department (ED) visits attributed to
      selected analgesic-containing medications. METHODS: We used a nationally
      representative public health surveillance system to provide estimates of adverse
      events identified in EDs, and a national telephone survey to provide estimates of
      selected analgesic-containing medication usage in the US population, 2004-2005.
      Analysis was restricted to products containing acetaminophen, aspirin, ibuprofen,
      or naproxen. Types of adverse events and outcomes were compared. Estimated
      numbers and rates of ED visits were calculated by analgesic groupings and patient
      age groups. RESULTS: The estimated overall rate of ED visits attributed to
      analgesic-containing medications was 1.6 visits /100,000 users per week. The very
      old and very young had the highest rates; there were minimal differences in rates
      by patient gender. Acetaminophen was the attributed drug with the most estimated
      ED visits and generally had the highest rates of ED visits. The highest estimated
      rate for a specific product group was among subjects 18-64 years of age taking
      narcotic-acetaminophen products (8.9 ED visits /100,000 users per week). Overall,
      12% of patients presenting to EDs with analgesic-attributed events were
      hospitalized. CONCLUSIONS: Rates of ED visits due to analgesics vary depending on
      the age of the patient and the product; most do not result in hospitalization.
      Although the rate of emergency visits is relatively low, because of the wide use
      of the analgesics, public health impact is considerable.

PMID- 19116956
TI  - Questionnaire design and the recall of pharmacological treatments: a systematic
      review.
AB  - PURPOSE: We aimed to review systematically the published evidence regarding the
      effect of questionnaire design on the recall of pharmacological treatments.
      METHODS: The electronic databases Pubmed, EMBASE, and Cochrane Library were
      searched from inception to October 2007, using the following search terms: drug
      utilization, pharmaceutical preparations, pharmacoepidemiology, validation
      studies, methods, epidemiologic methods, interviews, data collection, and
      questionnaires. Drug utilization studies comparing different types of
      questionnaire or methods of questionnaire administration were included. Backward
      and forward citation tracking were also conducted. RESULTS: Eight studies were
      included in the systematic review, comparing questions asking for specific drugs
      or indications with open-ended questions (n = 5), evaluating the use of memory
      aids (n = 1), or studying the influence of response order on recall (n = 2). The
      studies were heterogeneous, namely regarding the populations evaluated (e.g.,
      pregnant women, hypertensive patients, general population), mode of questionnaire
      administration (e.g., personal or telephone interview, self-administered), recall
      period (e.g., current use, 1 week, previous episode of a disease), or drugs
      evaluated (e.g., analgesics, antimalarials, all medicines). Despite the lack of
      standardization in presentation of results, the prevalence of drug use may vary
      between 5 and 40% when drug names and indications or pictures are used as memory
      aids, or as a result of primacy effects in self-administered questionnaires. The
      yielding of the questionnaires depended on the pharmacological groups evaluated.
      CONCLUSIONS: Scientific work regarding methods for drug utilization data
      collection is scarce. The available evidence highlights the importance of knowing
      the questionnaire characteristics for a proper interpretation of results from
      drug utilization studies.

PMID- 19116957
TI  - Inconsistency of response to conscious and unconscious motor imagery in complex
      regional pain syndrome: Comment on the article by Moseley et al.

PMID- 19116958
TI  - Recovery: what does this mean to patients with low back pain?
AB  - OBJECTIVE: To explore patients' perceptions of recovery from low back pain, about
      which little is known. METHODS: A qualitative study was conducted in which 36
      participants, either recovered or unrecovered from low back pain, participated in
      focus groups. Interviews were audiorecorded and transcribed verbatim. Framework
      analysis was used to identify emergent themes and domains of recovery. RESULTS:
      Patients' views of recovery encompassed a range of factors that can be broadly
      classified into the domains of symptom attenuation, improved capacity to perform
      a broad scope of self-defined functional activities, and achievement of an
      acceptable quality of life. An interactive model is proposed to describe the
      relationships between these domains, cognitive appraisal of the pain experience,
      and self-rated recovery. Pain attenuation alone was not a reliable indicator of
      recovery. CONCLUSION: The construct of recovery for typical back pain patients
      seeking primary care is more complex than previously recognized and is a highly
      individual construct, determined by appraisal of the impact of symptoms on daily
      functional activities as well as quality of life factors. These findings will be
      valuable for reassessing how to optimize measures of recovery from low back pain
      by addressing the spectrum of factors patients consider meaningful.

PMID- 19116959
TI  - Identification of relevant concepts of functioning in daily life in people with
      systemic lupus erythematosus: A patient Delphi exercise.
AB  - OBJECTIVE: To identify the most important and relevant concepts of daily
      functioning from the perspective of patients with systemic lupus erythematosus
      (SLE). METHODS: We conducted a consensus-building, 3-round, electronic mail
      survey with SLE patients using the Delphi technique. The Delphi technique is a
      structured communication process with 4 key characteristics: anonymity, iteration
      with controlled feedback, statistical group response, and informed input. The
      concepts contained in the answers of the patients were extracted and linked to
      the International Classification of Functioning, Disability and Health (ICF).
      RESULTS: Of the total 225 participants, 194 (86.2%) completed the questionnaires
      from all 3 Delphi rounds. In total, after the third Delphi round, 307 concepts
      were identified. Ninety concepts (55 in the domain body functions and structures,
      16 in activities and participation, and 19 in environmental factors) were
      considered relevant by at least 50% of the participants in the third round and
      linked to the ICF. Twelve concepts were considered important by at least 75% of
      the participants. CONCLUSION: The high number of concepts resulting from this
      large-scale patient Delphi approach underlines the great variety of SLE patients'
      problems in daily functioning. The results of this patient Delphi project
      supplement the findings of our focus-group study in establishing a comprehensive
      overview of the patient perspective in SLE.

PMID- 19116960
TI  - Effects of cryotherapy on arthrogenic muscle inhibition using an experimental
      model of knee swelling.
AB  - OBJECTIVE: Arthrogenic muscle inhibition (AMI) contributes to quadriceps weakness
      and atrophy in knee arthritis and following joint injury. This laboratory-based
      study examined the efficacy of cryotherapy in reducing quadriceps AMI caused by
      intraarticular swelling. METHODS: Sixteen subjects without knee pathology
      participated, and were randomly assigned to a cryotherapy (n = 8) or control (n =
      8) group. Surface electromyography (EMG) from vastus medialis and quadriceps
      torque measurements were recorded during maximum effort isometric contractions.
      All subjects then received an experimental joint infusion, whereby dextrose
      saline was injected into the knee to an intraarticular pressure of 50 mm Hg. EMG
      and torque measurements were repeated. Thereafter, the cryotherapy group had ice
      applied to the knee for 20 minutes while the control group did not receive an
      intervention. EMG and torque measurements were again collected. Quadriceps peak
      torque, muscle fiber conduction velocity (MFCV), and the root mean square (RMS)
      of EMG signals from vastus medialis were analyzed. RESULTS: Quadriceps peak
      torque, MFCV, and RMS decreased significantly following joint infusion (P < or =
      0.001). Cryotherapy led to a significant increase in quadriceps torque and MFCV
      compared with controls (P < 0.05). The difference in RMS did not reach
      statistical significance (P = 0.13). CONCLUSION: The study demonstrated that
      cryotherapy is effective in reducing AMI induced by swelling. Cryotherapy may
      allow earlier and more effective quadriceps strengthening to occur in patients
      with knee joint pathology.

PMID- 19116962
TI  - Inclusion of glucocorticoids in recommendations for the use of nonbiologic and
      biologic disease-modifying antirheumatic drugs in rheumatoid arthritis: Comment
      on the article by Saag et al.

PMID- 19116963
TI  - Risk factors for thrombosis and primary thrombosis prevention in patients with
      systemic lupus erythematosus with or without antiphospholipid antibodies.
AB  - OBJECTIVE: Antiphospholipid antibodies (aPL), namely anticardiolipin antibodies
      (aCL) and lupus anticoagulant (LAC), have been associated with an increased risk
      of thrombosis in systemic lupus erythematosus (SLE). We examined additional
      thrombosis risk factors (aPL profile, SLE-related, and traditional risk factors)
      and the primary thrombosis prevention in SLE patients with and without aPL.
      METHODS: All SLE patients with positive aPL but without previous thrombotic
      manifestations who were regularly followed up at our department (n = 144) and 144
      age- and sex-matched SLE patients with negative aPL were included in this study.
      The median followup times were 104 and 112 months, respectively. The demographic,
      clinical, laboratory, and treatment characteristics and the traditional
      thrombosis risk factors were recorded. RESULTS: The thrombosis rate was 29 per
      144 aPL-positive patients (20.1%) and 11 per 144 aPL-negative patients (7.6%; P =
      0.003). In multiadjusted analysis, significant predictors of thrombosis were male
      sex (hazard ratio [HR] 6.25, P < 0.01), LAC (HR 3.48, P = 0.04), and constantly
      positive aCL (HR 5.87, P = 0.01) for aPL-positive patients, while male sex (HR
      7.14, P = 0.03) and hypertension were predictors for aPL-negative patients (HR
      6.49, P = 0.03). Additionally, the duration of low-dose aspirin treatment played
      a protective role against thrombosis in aPL-positive patients (HR per month 0.98,
      P = 0.05), as did the duration of hydroxychloroquine in both aPL-positive (HR per
      month 0.99, P = 0.05) and aPL-negative patients (HR per month 0.98, P = 0.04).
      CONCLUSION: Independent predictors of thrombosis for aPL-positive patients were
      male sex, LAC, and constantly positive aCL, and for aPL-negative patients were
      male sex and hypertension. The duration of low-dose aspirin use played a
      protective role against thrombosis in aPL-positive patients as did the duration
      of hydroxychloroquine in both groups.

PMID- 19116964
TI  - Patient-reported outcomes for arthritis: time to focus on personal life impact
      measures?

PMID- 19116965
TI  - Patient-reported outcomes in a randomized trial comparing four different
      treatment strategies in recent-onset rheumatoid arthritis.
AB  - OBJECTIVE: To investigate the effectiveness of 4 different treatment strategies
      for recent-onset rheumatoid arthritis (RA) on 2-year patient-reported outcomes,
      including functioning and quality of life. METHODS: A total of 508 patients with
      recent-onset RA were randomly assigned to 1) sequential monotherapy, 2) step-up
      combination therapy, both starting with methotrexate, 3) initial combination
      therapy, including a tapered high-dose prednisone, or 4) initial combination
      therapy with methotrexate and infliximab. Treatment was adjusted every 3 months
      if the Disease Activity Score (DAS) remained >2.4. The McMaster Toronto Arthritis
      Patient Preference Disability Questionnaire, the Short Form 36 (SF-36), and
      scores for pain, global health, and disease activity measured on a 100-mm visual
      analog scale (VAS) were compared between groups at baseline and every 3 months
      thereafter for 2 years. RESULTS: After 2 years, all patient-reported outcomes had
      improved significantly from baseline, irrespective of the treatment strategy. SF
      36 subscale scores approached population norms for 3 physical components, and
      achieved population norms (P > 0.05) for bodily pain and 4 mental components.
      Improvement in functioning, VAS scores, and physical items of the SF-36 occurred
      significantly earlier in patients treated with initial combination therapies (all
      comparisons after 3 months: overall P < 0.001; P < 0.05 for groups 1 and 2 versus
      groups 3 and 4). CONCLUSION: All 4 DAS-driven treatment strategies resulted in
      substantial improvements in functional ability, quality of life, and self
      assessed VAS scores after 2 years. Initial combination therapy led to
      significantly faster improvement in all patient-reported measures.

PMID- 19116966
TI  - Development and testing of a decision board to help clinicians present treatment
      options to lupus nephritis patients in Brazil.
AB  - OBJECTIVE: Decision boards (DBs) help clinicians present options and include
      patients in the decision-making process. Our objective was to describe the steps
      to develop a DB to support shared decision making and assess reliability and
      construct validity. METHODS: Systemic lupus erythematosus (SLE) scenarios were
      designed with the support of experts for disease severity, potential side
      effects, and outcomes. The DB comprised clinical information, 2 different
      treatment options (oral and intravenous), a description of the potential to
      control SLE within 5 years, and a list of potential side effects. Patients
      selected what they thought would be the 3 worst side effects and were informed of
      the probability that these would occur. We presented the DB to 172 patients who
      were asked to select and justify 1 treatment option. Reliability was assessed by
      kappa statistics. Construct validity was tested by an a priori hypothesis,
      analyzing the correlation between treatment decision and side effects selected,
      self-assessment score, educational level, and clinical aspects. RESULTS: Patients
      favored oral medication, and side effects most often listed were iatrogenic
      cancer (44.2%), hair loss (21.6%), and severe infection (19.1%). Justifications
      were risk (48.9%), practicality (36.6%), effectiveness (12.2%), and risk-benefit
      tradeoff (2.3%). Reliability was similar to that found in the test phase (kappa =
      0.689, P < 0.001). Validity was tested by prediction of treatment decision based
      on the undesirable side effects selected (P = 0.047). DB content was clear and
      easy for all patients to understand (P = 0.05). Immunosuppressive drugs
      influenced patient decisions (P = 0.006). CONCLUSION: DB is a reliable and valid
      instrument to assess SLE patient preference.

PMID- 19116967
TI  - How to evaluate and improve the reliability of power Doppler ultrasonography for
      assessing enthesitis in spondylarthritis.
AB  - OBJECTIVE: To evaluate and improve the reliability of power Doppler
      ultrasonography (PDUS) for detecting and scoring enthesitis in patients with
      spondylarthitis, using a 3-step procedure. METHODS: In the first step, we
      evaluated the reliability of 5 sonographers by bilaterally scanning 5 entheses
      twice in 5 patients. In the second step, starting from disagreements observed
      during the first step, we established consensus guidelines. The sonographers'
      implementation was further evaluated in 2 reliability exercises: one on 60 PDUS
      enthesitis images and the other by scanning 5 new patients. In the third step, we
      performed a final reliability evaluation of 5 additional patients after 1 year.
      Kappa coefficients (kappa) as well as variance component analysis (VCA) and
      generalizability theory (GT) were used to assess reliability. RESULTS: The
      initial intra- and interobserver reliability were poor, especially for detecting
      and scoring Doppler signal. VCA and GT showed that most variability was accounted
      for by interaction between sonographer and enthesis. Implementation of consensus
      guidelines was associated with a significant improvement in Doppler reliability
      between the first and second steps (mean interobserver kappa increased from 0.13
      to 0.51 for binary Doppler scoring in patients; P < 0.005), which persisted in
      the third step (mean interobserver kappa = 0.57). The high GT coefficients
      reached in the last steps supported such improvement. CONCLUSION: The 3-step
      procedure used in this study to standardize PDUS technique was associated with a
      significant improvement in interobserver reliability for detecting enthesitis in
      spondylarthritis patients. Such an approach can be useful to standardize PDUS
      assessment of musculoskeletal disorders.

PMID- 19116968
TI  - Effectiveness of treatment of calcific tendinitis of the shoulder by disodium
      EDTA.
AB  - OBJECTIVE: To evaluate the effectiveness of disodium EDTA administration in the
      treatment of calcific tendinitis of the shoulder. METHODS: Eighty patients with
      radiographically verified calcific tendinitis of the shoulder were enrolled
      between September 2001 and October 2003. Patients were randomly assigned to
      either a study group (n = 40) or a control group (n = 40). Pain and functional
      level were evaluated before and after treatment and at 1-year followup.
      Radiographic modifications in calcifications were evaluated before and after
      treatment. Disodium EDTA was administered through single needle mesotherapy and
      15 minutes of pulsed-mode 1 MHz-ultrasound. RESULTS: The study group displayed
      improvement in all of the parameters analyzed after treatment and at the 1-year
      followup. Calcifications disappeared completely in 62.5% of the patients in the
      study group and partially in 22.5%; calcifications partially disappeared in only
      15% of the patients in the control group, and none displayed a complete
      disappearance. CONCLUSION: Our results suggest that the use of disodium EDTA for
      the management of calcific tendinitis of the shoulder is safe and effective,
      leading to a significant reduction in pain, improvement in shoulder function, and
      disappearance of calcifications after 4 weeks, without adverse effects.

PMID- 19116969
TI  - (Mis)understanding in patient-health care provider communication about total knee
      replacement.
AB  - OBJECTIVE: To examine whether communication factors affect health care provider
      and patient agreement on the need for, risks of, and benefits of joint
      replacement, and also whether degree of agreement predicts patient satisfaction
      and intent to follow treatment recommendations. METHODS: Health care providers (n
      = 27) and patients (n = 74) with severe osteoarthritis (OA) were recruited from
      clinics in Houston, Texas. Patients completed a baseline survey prior to the
      consultation. After the visit, patients and providers completed measures of the
      severity of the patient's OA, the expected benefits of total knee replacement
      (TKR), and concern about surgical complications. Patients also completed
      satisfaction and intent to adhere measures. Provider communication and patient
      participation were measured by patient self-report and by observers' codings of
      audiorecordings of the consultations. RESULTS: Provider-patient agreement was
      modest to poor regarding severity of the patient's OA and the expected benefits
      and risks of TKR. Providers and patients were more aligned on the patient's OA
      severity when providers used more partnership building but spent less time simply
      giving information. Differences between providers' and patients' concerns about
      surgery were greater when patients were less participatory, African American, or
      expressed lower trust in their doctors. Patient satisfaction and intent to adhere
      were predicted by provider-patient agreement on the benefits of TKR. CONCLUSION:
      Patients and providers often differ in their beliefs about the need for, risks
      of, and benefits of TKR, and these differences can affect patient satisfaction
      and commitment to treatment. Facilitating active patient participation might
      contribute to greater physician-patient agreement on the patient's concerns about
      OA and surgical interventions.

PMID- 19116970
TI  - Pneumomediastinum in interstitial lung disease associated with dermatomyositis
      and polymyositis.
AB  - OBJECTIVE: Spontaneous pneumomediastinum is a rare complication of
      dermatomyositis (DM) and polymyositis (PM). The aim of this study was to
      characterize this complication and determine its prognostic factors. METHODS: We
      retrospectively collected a multicenter series of PM/DM cases complicated by
      pneumomediastinum. We analyzed all published cases and combined those that were
      exploitable with ours for an investigation of the factors associated with poor
      survival. RESULTS: We collected 11 PM/DM cases complicated by interstitial lung
      disease and pneumomediastinum. Five of the 9 DM patients had clinically
      amyopathic DM without muscle weakness and high serum creatine kinase levels. The
      outcome was favorable in 7 of these patients and 6 had no sequelae. In total,
      approximately 25% of our patients of the 21 analyzable cases studied died within
      1 month. With a median followup of 240 days, the cumulative estimated Kaplan
      Meier survival rate was 64% at 1 year and 55% at 2 years. Poor survival was
      associated with absence of muscle weakness (P = 0.02), initial low vital capacity
      (P = 0.006), and initial low carbon monoxide diffusion capacity (P = 0.04).
      CONCLUSION: In this first large series of patients with connective tissue disease
      complicated by pneumomediastinum to be reported, most patients had DM and half
      amyopathic DM, as in previous reports. Pneumomediastinum may occur before DM
      diagnosis and may thus reveal DM with minimal or no muscle involvement. Death was
      associated with an absence of muscle weakness and severe pulmonary involvement
      before the onset of pneumomediastinum. Corticosteroids and immunosuppressive
      therapy can result in complete recovery, as in half our cases.

PMID- 19116973
TI  - A case-control study to assess sensitivity and specificity of a questionnaire for
      the detection of hip and knee osteoarthritis.
AB  - OBJECTIVE: To assess the performance of a telephone-administered questionnaire
      suitable for use in 2-phase surveys in the detection of symptomatic hip and knee
      osteoarthritis (OA) cases. METHODS: A questionnaire was designed based on typical
      symptoms and self-reported OA diagnosis. Three groups of subjects were
      consecutively enrolled from rheumatology units at French university hospitals.
      The disease status, based on American College of Rheumatology criteria, was first
      confirmed by a rheumatologist. Subjects then completed the screening
      questionnaire administered by interviewers unaware of the diagnosis and the
      clinical examination results. Three screening strategies were evaluated. RESULTS:
      In all, 119 subjects with hip OA, 137 with knee OA, and 111 subjects with other
      rheumatic diseases with lower extremity symptoms were recruited. The highest
      sensitivity for both hip and knee OA was obtained with the strategy based on
      reporting the presence or absence of symptoms (>96%). The specificity of this
      strategy was low (42% for both joints). When taking into account the self
      reported OA diagnosis, the sensitivity slightly decreased (>91%), and the
      specificity increased greatly, from 76% to 78%. The highest specificity was
      obtained with the third strategy, requiring a rheumatologist opinion (from 82% to
      85%) at the expense of lower sensitivity (>90%). CONCLUSION: The questionnaire
      tested in this study is a simple, valid, and reliable instrument to screen
      symptomatic hip and knee OA. As such, it fails to reach complete accuracy and
      clinical examination and radiographs remain necessary for complete ascertainment
      procedure.

PMID- 19116974
TI  - The cost of systemic sclerosis.
AB  - OBJECTIVE: To assess costs related to systemic sclerosis (SSc) and their
      determinants. METHODS: The Canadian Scleroderma Research Group is comprised of 15
      centers contributing to a registry of adult patients with SSc. Available cross
      sectional data included clinical variables and standardized measures of health
      resource use and time loss. Annualized averages of direct medical costs were
      calculated by multiplying health service utilization levels by the appropriate
      unit prices, determined from government fee schedules, professional associations,
      and other sources. Indirect costs were calculated from the subjects' self
      reported time loss related to illness and to seeking health care, as well as
      caregiver time losses. Costs were represented in 2007 Canadian dollars. RESULTS:
      In the sample of 457 patients with SSc, the average direct cost per patient was
      $5,038 per year (95% confidence interval [95% CI] $4,400, $5,676). Regarding
      indirect costs, the value of potential productivity loss related to paid labor
      was estimated at an average of $5,345 per patient per year (95% CI $4,598,
      $6,092), and the cost of lost productivity related to unpaid labor contributed
      another $8,070 per patient annually. The average total annual cost was estimated
      at $18,453 (95% CI $16,598, $20,308) per patient. Total annual costs were
      strongly associated with younger age, greater disease severity, and poorer health
      status. CONCLUSION: Costs related to SSc are considerable, and there is a high
      impact of disease severity and health status on economic burden.

PMID- 19116975
TI  - Time to treatment as an important factor for the response to methotrexate in
      juvenile idiopathic arthritis.
AB  - OBJECTIVE: Methotrexate (MTX) is the most commonly used disease-modifying
      antirheumatic drug in juvenile idiopathic arthritis (JIA). Currently, individual
      response to MTX cannot be reliably predicted. Identification of clinical and
      genetic factors that influence the response to MTX could be helpful in realizing
      the optimal treatment for individual patients. METHODS: A cohort of 128 JIA
      patients treated with MTX were studied retrospectively. Eleven clinical
      parameters and genotypes of 6 single nucleotide polymorphisms in 5 genes related
      to the mechanism of action of MTX were compared between MTX responders and
      nonresponders using a multivariate regression analysis. RESULTS: The time from
      diagnosis to start of MTX treatment, physician's global assessment at baseline,
      and the starting dose were significantly associated with the response to MTX at 6
      months after initiation. Patients with a shorter time from diagnosis to start of
      MTX and a higher disease activity according to the physician but with a lower MTX
      dose showed an increased response. The effect of the starting dose on MTX
      response seemed to be mainly due to the influence of the systemic JIA subtype.
      The time from diagnosis to start of MTX treatment and physician's global
      assessment at baseline were highly correlated. Therefore, the precise effect size
      of each independent variable could not be determined. CONCLUSION: In children
      with JIA, the time from diagnosis to start of MTX appears to be an important
      factor for MTX response. Our results suggest that an earlier start of MTX
      treatment will lead to an increased response.

PMID- 19116976
TI  - Preparing for adulthood: health care transition counseling for youth with
      arthritis.
AB  - OBJECTIVE: To determine the proportion of adolescents with arthritis who receive
      health care transition services and to compare the rates with those reported for
      adolescents with other special health care needs and adolescents with diabetes.
      METHODS: We used data from the 2005-2006 National Survey of Children with Special
      Health Care Needs. A parent/guardian identified youth ages 12-17 years with
      arthritis (n = 1,052), diabetes (n = 389), and special health care needs (n =
      18,189). Four questions examined the extent to which providers discussed health
      care transition issues, including 1) transfer of care to adult providers, 2)
      health care needs of adults, 3) acquiring health insurance, and 4) encouraging
      self-care responsibility. Bivariate comparisons assessed the associations between
      sociodemographic characteristics and health care transition services, and
      multivariate regression models compared outcomes between conditions. RESULTS:
      Many adolescents with arthritis are being encouraged to assume self-care
      responsibilities (74.8%); fewer discussed how health needs will change in
      adulthood (52.1%), acquiring insurance (22.5%), or transferring care to a
      provider who sees adults (19.0%). These results are similar to youth with other
      special health care needs, but behind youth with diabetes. CONCLUSION: Among this
      sample of US adolescents, many report discussions about health care needs and
      self-management, but few are addressing critical aspects of the transition to
      adult-oriented health care.

PMID- 19116977
TI  - Pain induced by injection of hypertonic saline into the infrapatellar fat pad and
      effect on coordination of the quadriceps muscles.
AB  - OBJECTIVE: Musculoskeletal conditions of the knee involve changes in sensorimotor
      function, but it is unclear whether these changes are a cause or result of pain.
      Induction of experimental pain may help solve this issue. Although this is
      commonly achieved by injection of hypertonic saline into muscle, muscle is
      commonly not the source of pain. This study investigated whether pain induced by
      injection of saline into the infrapatellar fat pad changes motor control of the
      quadriceps muscles of the knee. METHODS: Ten participants performed a
      standardized task involving ascending and descending a series of steps.
      Electromyographic activity (EMG) of vastus medialis obliquus (VMO) and vastus
      lateralis (VL) was recorded with surface electrodes. Trials were conducted
      without pain, with anterior knee pain induced by injection (0.25 ml) of
      hypertonic saline (5%) into the infrapatellar fat pad, with anticipation of pain
      associated with unpredictable electrical shocks to the knee, and 20 minutes after
      pain cessation. EMG onset and amplitude were analyzed. RESULTS: When participants
      ascended the steps with pain, the onset of VMO EMG was delayed relative to that
      of VL, in contrast to simultaneous or earlier activation of VMO EMG in the pre-
      and postpain trials. VL EMG amplitude was decreased significantly from the
      control condition. CONCLUSION: These data show that alterations in coordination
      of knee muscle activity can be caused by pain, even when it is of nonmuscle
      origin. Treatment of pain is therefore important to facilitate performance of the
      quadriceps muscles, which are essential for locomotor and functional tasks as
      well as for knee stability.

PMID- 19116978
TI  - Musculoskeletal sonography in juvenile systemic lupus erythematosus.
AB  - OBJECTIVE: To demonstrate the role of sonography in depicting periarticular
      changes in juvenile systemic lupus erythematosus (SLE) and to find out whether
      certain tendons in juvenile SLE patients were different from those of healthy
      controls. METHODS: Thirty juvenile SLE patients (27 female, 3 male) were
      recruited for this study. Sonographic evaluations were performed in the knee,
      ankle, elbow, wrist, and metacarpophalangeal (MCP) joints on the nondominant
      sides of the individuals. For comparison, 32 healthy volunteers were included as
      a control group. RESULTS: Knee effusion was observed more frequently in the
      juvenile SLE group compared with the control group (P = 0.00). When tendon
      thickness measurements were compared between the groups, flexor and extensor
      tendons of the third finger (at MCP joint level) of juvenile SLE patients were
      found to be thinner (P = 0.04 and P = 0.03, respectively). Tendon thickness
      values did not correlate with disease duration or SLE disease activity index
      scores (P > 0.05). CONCLUSION: The main findings of our study were relevant with
      1) increased involvement of the knee, ankle, hand extensor tendons, wrist, elbow,
      and hand flexor tendons (in decreasing order of frequencies) in juvenile SLE, and
      2) decreased extensor/flexor tendon thicknesses in the hands of juvenile SLE
      patients. Physicians should be aware of the potentially disabling scenario of
      tendon pathologies. Defining the extent of joint and tendon pathologies in
      juvenile SLE may guide us in the management of the disease.

PMID- 19116979
TI  - Differences in long-term disease activity and treatment of adult patients with
      childhood- and adult-onset systemic lupus erythematosus.
AB  - OBJECTIVE: To compare differences in long-term outcome between adults with
      childhood-onset (age at diagnosis <18 years) systemic lupus erythematosus (SLE)
      and with adult-onset SLE. METHODS: Data were derived from the University of
      California Lupus Outcomes Study, a longitudinal cohort of 885 adult subjects with
      SLE (90 childhood-onset [cSLE], 795 adult-onset [aSLE]). Baseline and 1-year
      followup data were obtained via structured 1-hour telephone interviews conducted
      between 2002 and 2006. Using self-report data, differences in organ involvement
      and disease morbidity, current disease status and activity, past and current
      medication use, and number of physician visits were compared, based on age at
      diagnosis of SLE. RESULTS: Average disease duration for the cSLE and aSLE
      subgroups was 16.5 and 13.4 years, respectively, and mean age at followup was
      30.5 and 49.9 years, respectively. When compared with aSLE subjects, cSLE
      subjects had a higher frequency of SLE-related renal disease, whereas aSLE
      subjects were more likely to report a history of pulmonary disease. Rates of
      clotting disorders, seizures, and myocardial infarction were similar between the
      2 groups. At followup, cSLE subjects had lower overall disease activity, but were
      more likely to be taking steroids and other immunosuppressive therapies. The
      total number of yearly physician visits was similar between the 2 groups,
      although cSLE subjects had a higher number of nephrology visits. CONCLUSION: This
      study demonstrates important differences in the outcomes of patients with cSLE
      and aSLE, and provides important prognostic information about long-term SLE
      disease activity and treatment.

PMID- 19116980
TI  - A 62-year-old man with wrist and hand pain.

PMID- 19116983
TI  - Comparative proteomic analysis of mesenchymal stem cells derived from human bone
      marrow, umbilical cord, and placenta: implication in the migration.
AB  - Umbilical cord (UC) and placenta (P) have been suggested as alternatives to bone
      marrow (BM) as sources of mesenchymal stem cells (MSC) for cell therapy, with
      both UC- and P-MSC possess immunophenotypic and functional characteristics
      similar to BM-MSC. However, their migration capacity, which is indispensable
      during tissue regeneration process, is unclear. Under defined conditions, the
      migration capacity of BM- and P-MSC was found 5.9- and 3.2-folds higher than that
      of UC-MSC, respectively. By the use of 2-DE and combined MS and MS/MS analysis,
      six differentially expressed proteins were identified among these MSC samples,
      with five of them known to be involved in cell migration as migration enhancing
      or inhibiting proteins. Consistent with their migration capacity, the levels of
      migration enhancing proteins including cathepsin B, cathepsin D and
      prohibitin,were significantly lower in UC-MSC when compared with those in BM- and
      P-MSC. For the migration inhibiting proteins such as plasminogen activator
      inhibitor-1 (PAI-1) and manganese superoxide dismutase, higher expression was
      found in the UC-MSC. We also showed that the overexpression of the PAI-1 impaired
      the migration capacity of BM- and P-MSC while silencing of PAI-1 enhanced the
      migration capacity of UC-MSC. Our study indicates that PAI-1 and other migration
      related proteins are pivotal in governing the migration capacity of MSC.

PMID- 19116987
TI  - Effect of cadmium exposure on the globin protein expression in 4th instar larvae
      of Chironomus riparius Mg. (Diptera: Chironomidae): an ecotoxicoproteomics
      approach.
AB  - In order to identify Chironomus hemoglobin (Hb) as a biomarker of ecotoxicity
      monitoring; herein, the effects of cadmium chloride (Cd) on Hb parameters were
      investigated in the 4th instar larvae of Chironomus riparius. The expressions of
      globin mRNA and hemolymph protein, using ecotoxicoproteomic approach, were
      investigated. Conventional ecotoxicity tests were also conducted to validate the
      ecotoxicological relevance of the response of Chironomus Hb as a biomarker. The
      proteomic analysis indicated that exposure to Cd lead alteration in the
      expression of hemolymph protein, with the total expressions of 12 hemolymph
      protein spots decreasing in response to treatment, with that of two increasing in
      response to Cd exposure. In addition, all of the spots differentially expressed
      in response to Cd treatment were identified as globin proteins. The decreased
      total Hb content observed in the hemolymph of larvae exposed to Cd suggested that
      the decreased expression of selected globin proteins in response to Cd exposure
      impacted on Hb synthesis. The overall results suggested that Hb could be a target
      molecule for exposure to Cd in C. riparius, with a proteomic approach appearing
      to be an ideal tool for the discovery of biomarkers in ecotoxicological research.

PMID- 19116988
TI  - Identification of extracellular delta-catenin accumulation for prostate cancer
      detection.
AB  - BACKGROUND: Prostate cancer is the second leading cause of cancer death in men,
      and early detection is essential to reduce mortality and increase survival. delta
      Catenin is a unique beta-catenin superfamily protein primarily expressed in the
      brain but is upregulated in human prostatic adenocarcinomas. Despite its close
      correlation with the disease, it is unclear whether delta-catenin presents the
      potential in prostate cancer screening because it is an intracellular protein. In
      this study, we investigated the hypothesis of delta-catenin accumulation in the
      urine of prostate cancer patients and its potential pathways of excretion into
      extracellular milieu. METHODS: Prostate cancer cell cultures, human tissue
      biopsies, and voided urines were characterized to determine extracellular delta
      catenin accumulation and co-isolation with exosomes/prostasomes. RESULTS: We
      identified delta-catenin in culture media and in the stroma of human prostate
      cancer tissues. In PC-3 cells in culture, delta-catenin was partially co
      localized and co-isolated with raft-associated membrane protein caveolin-1 and
      glycosylphosphatidylinositol-anchored protein CD59, suggesting its potential
      excretion into extracellular milieu through exosome/prostasome associated
      pathways. Interference with endocytic pathway using wortmannin did not block
      prostasome excretion, but delta-catenin overexpression promoted the extracellular
      accumulation of caveolin-1. delta-Catenin, caveolin-1, and CD59 were all detected
      in cell-free human voided urine prostasomes. delta-Catenin immunoreactivity was
      significantly increased in the urine of prostate cancer patients (P < 0.0005).
      CONCLUSIONS: This study demonstrated, for the first time, the extracellular
      accumulation of delta-catenin in urine supporting its potential utility for non
      invasive prostate cancer detection.

PMID- 19116989
TI  - Switching of vascular phenotypes within a murine breast cancer model induced by
      angiopoietin-2.
AB  - Sustained growth of solid tumours can rely on both the formation of new and the
      co-option of existing blood vessels. Current models suggest that binding of
      angiopoietin-2 (Ang-2) to its endothelial Tie2 receptor prevents receptor
      phosphorylation, destabilizes blood vessels, and promotes vascular permeability.
      In contrast, binding of angiopoietin-1 (Ang-1) induces Tie2 receptor activation
      and supports the formation of mature blood vessels covered by pericytes. Despite
      the intense research to decipher the role of angiopoietins during physiological
      neovascularization and tumour angiogenesis, a mechanistic understanding of
      angiopoietin function on vascular integrity and remodelling is still incomplete.
      We therefore assessed the vascular morphology of two mouse mammary carcinoma
      xenotransplants (M6378 and M6363) which differ in their natural angiopoietin
      expression. M6378 displayed Ang-1 in tumour cells but no Ang-2 in tumour
      endothelial cells in vivo. In contrast, M6363 tumours expressed Ang-2 in the
      tumour vasculature, whereas no Ang-1 expression was present in tumour cells. We
      stably transfected M6378 mouse mammary carcinoma cells with human Ang-1 or Ang-2
      and investigated the consequences on the host vasculature, including
      ultrastructural morphology. Interestingly, M6378/Ang-2 and M6363 tumours
      displayed a similar vascular morphology, with intratumoural haemorrhage and non
      functional and abnormal blood vessels. Pericyte loss was prominent in these
      tumours and was accompanied by increased endothelial cell apoptosis. Thus,
      overexpression of Ang-2 converted the vascular phenotype of M6378 tumours into a
      phenotype similar to M6363 tumours. Our results support the hypothesis that Ang
      1/Tie2 signalling is essential for vessel stabilization and endothelial
      cell/pericyte interaction, and suggest that Ang-2 is able to induce a switch of
      vascular phenotypes within tumours.

PMID- 19116990
TI  - Epithelial-mesenchymal transition induced by biliary innate immunity contributes
      to the sclerosing cholangiopathy of biliary atresia.
AB  - Infections of Reoviridae consisting of a double-stranded RNA (dsRNA) genome and
      the biliary innate immune response to dsRNA are implicated in the
      aetiopathogenesis of biliary atresia (BA). Epithelial-mesenchymal transition
      (EMT) has recently been proposed as a mechanism behind the sclerosing cholangitis
      in BA. We hypothesized that the innate immune response to dsRNA in biliary
      epithelial cells plays an important role in peribiliary fibrosis via biliary EMT.
      Experiments using cultured human biliary epithelial cells revealed that
      stimulation with poly(I : C) (a synthetic analogue of viral dsRNA) increased the
      expression of basic fibroblast growth factor (bFGF, an EMT-inducer), S100A4 (a
      mesenchymal marker) and Snail (a transcriptional factor), and decreased that of
      epithelial markers (biliary-type cytokeratin 19 and E-cadherin) and Bambi (TGF
      beta1 pseudoreceptor). The expression of TGF-beta1 (EMT-inducer) and vimentin (a
      mesenchymal marker) was not affected by poly(I : C). Both EMT-inducers, bFGF and
      TGF-beta1, evoked a decrease and increase in the expression of the epithelial
      markers and of vimentin respectively, and the expression of Bambi was down
      regulated on stimulation with bFGF. Combined treatment with bFGF and TGF-beta1
      quickly and completely induced a transformation of morphology as well as change
      from epithelial to mesenchymal features in cultured biliary epithelial cells.
      Immunohistochemistry revealed that biliary epithelial cells lining extrahepatic
      bile ducts and peribiliary glands in BA frequently show a lack of epithelial
      markers and an aberrant expression of vimentin. Moreover, the biliary epithelium
      showing sclerosing cholangitis expressed bFGF accompanied by bFGF-positive
      mononuclear cells. In conclusion, the EMT may contribute to the histogenesis of
      sclerosing cholangiopathy, and the biliary innate immune response to dsRNA
      viruses induces biliary epithelial cells to undergo EMT via the production of
      bFGF and the increased susceptibility to TGF-beta1 caused by the down-regulation
      of Bambi expression.

PMID- 19116991
TI  - Over-expression of metallothionein predicts chemoresistance in breast cancer.
AB  - Metallothionein (MT) plays a role in fundamental cellular processes such as
      proliferation, apoptosis and differentiation. We examined MT expression in women
      with invasive breast ductal carcinoma who underwent mastectomy/lumpectomy without
      neo-adjuvant treatment. We showed that MT was over-expressed in 87.9% of breast
      cancer tissues examined, with the mean percentage of positive cells at 30%. There
      were two patterns of MT expression: predominantly cytoplasmic in 75.9% and
      nuclear in 24.1% of MT-positive cases. Higher MT scores were associated with
      poorer histological grade (p = 0.009) but were independent of age, tumour size
      and oestrogen receptor status. For patients who were treated with adjuvant
      chemotherapy (cyclophosphamide/methotrexate/5 fluorouracil- or doxorubicin-based
      regimes), those with high MT expression had a significantly lower recurrence-free
      survival (p = 0.048), suggesting a role of MT in predicting disease recurrence.
      Down-regulation of MT in MCF-7 cells by silencing the MT-2A gene (the most
      abundantly expressed of the 10 known functional MT isoforms) increased
      chemosensitivity of the cells to doxorubicin. To examine the mechanisms
      underlying these clinical data, we used siRNAs to decrease MT-2A mRNA expression
      and protein expression. In MT down-regulated cells challenged with the IC(50)
      concentration of doxorubicin, we observed a significant reduction in cell
      viability. Cell cycle analysis also revealed a corresponding increase in
      apoptosis in the MT down-regulated cells following doxorubicin exposure, showing
      that down-regulation of MT increased susceptibility to doxorubicin cytotoxicity.
      The data suggest that MT could be a potential marker of chemoresistance and a
      molecular therapeutic target.

PMID- 19116993
TI  - Ruthenium complexes with cooperative PNP ligands: bifunctional catalysts for the
      dehydrogenation of ammonia-borane.

PMID- 19116994
TI  - Titanium-catalyzed hydroaminoalkylation of alkenes by C-H bond activation at sp3
      centers in the alpha-position to a nitrogen atom.

PMID- 19116992
TI  - Association of reported prostate cancer risk alleles with PSA levels among men
      without a diagnosis of prostate cancer.
AB  - BACKGROUND: Prostate specific antigen (PSA) is widely used for prostate cancer
      screening but its levels are influenced by many non cancer-related factors. The
      goal of the study is to estimate the effect of genetic variants on PSA levels.
      METHODS: We evaluated the association of SNPs that were reported to be associated
      with prostate cancer risk in recent genome-wide association studies with plasma
      PSA levels in a Swedish study population, including 1,722 control subjects
      without a diagnosis of prostate cancer. RESULTS: Of the 16 SNPs analyzed in
      control subjects, significant associations with PSA levels (P < or = 0.05) were
      found for six SNPs. These six SNPs had a cumulative effect on PSA levels; the
      mean PSA levels in men were almost twofold increased across increasing quintile
      of number of PSA associated alleles, P-trend = 3.4 x 10(-14). In this Swedish
      study population risk allele frequencies were similar among T1c case patients
      (cancer detected by elevated PSA levels alone) as compared to T2 and above
      prostate cancer case patients. CONCLUSIONS: Results from this study may have two
      important clinical implications. The cumulative effect of six SNPs on PSA levels
      suggests genetic-specific PSA cutoff values may be used to improve the
      discriminatory performance of this test for prostate cancer; and the dual
      associations of these SNPs with PSA levels and prostate cancer risk raise a
      concern that some of reported prostate cancer risk-associated SNPs may be
      confounded by the prevalent use of PSA screening.

PMID- 19116995
TI  - Easy copper-catalyzed synthesis of primary aromatic amines by couplings aromatic
      boronic acids with aqueous ammonia at room temperature.

PMID- 19116996
TI  - Sigma and pi donation in an unsupported uranium-gallium bond.

PMID- 19116997
TI  - Total synthesis of a protected aglycon of the kedarcidin chromophore.

PMID- 19116998
TI  - Interactions of small protected peptides with aminopyrazole derivatives: the
      efficiency of blocking a beta-sheet model in the gas phase.

PMID- 19116999
TI  - Preparation of rhodium nanoparticles in carbon dioxide induced ionic liquids and
      their application to selective hydrogenation.

PMID- 19117000
TI  - Cyclododecasulfur as a ligand: from gas-phase experiments to the crystal
      structures of [Cu(S12)(S8)]+ and [Cu(S12)(CH2Cl2)]+.

PMID- 19117001
TI  - A photoreactive ruthenium(II) complex tethered to a guanine-containing
      oligonucleotide: a biomolecular tool that behaves as a "seppuku molecule".

PMID- 19117002
TI  - "If pigs could fly" chemistry: a tutorial on the principle of microscopic
      reversibility.
AB  - Through a glass darkly: Several recent autocatalytic reaction models for the
      origin of homochirality have suggested ways in which one enantiomer of the
      product might be reconverted into the other by a recycling reaction in a closed
      system. These models are revealed to violate the principle of microscopic
      reversibility, a powerful tool for assessing the plausibility of proposed
      reaction networks even at far-from-equilibrium conditions.

PMID- 19117003
TI  - Total synthesis of bacilosarcins A and B.

PMID- 19117004
TI  - Synthesis, structure, and complexation properties of partially and completely
      reduced meso-octamethylporphyrinogens (calix[4]pyrroles).
AB  - New tricks for an old dog: Calixpyrroles bind anions efficiently and can be
      transformed into transition-metal complexes only under forcing conditions.
      Reducing the macrocycle creates a ligand that easily forms classical Werner
      complexes with copper, nickel, and palladium ions. The metal complexes present an
      array of four directed hydrogen bonds, which specifically bind the counterions
      (see picture; blue N, white H, green Cl, red Cu, Ni, or Pd).

PMID- 19117005
TI  - Exceptional selectivity in cyclopropanation reactions catalyzed by chiral
      cobalt(II)-porphyrin catalysts.

PMID- 19117006
TI  - Bifunctional dendrimers: from robust synthesis and accelerated one-pot
      postfunctionalization strategy to potential applications.
AB  - A fourth wheel: Two sets of bifunctional AB(2)C dendrimers having internal
      acetylene/azides and external hydroxy groups were constructed utilizing benign
      synthetic protocols. An in situ postfunctionalization strategy was successfully
      carried out to illustrate the chemoselective nature of these dendrimers. The
      dendrimers were also transformed into dendritic nanoparticles or utilized as
      dendritic crosslinkers for the fabrication hydrogels.

PMID- 19117007
TI  - Hypervalent bromine compounds: smaller, more reactive analogues of hypervalent
      iodine compounds.

PMID- 19117008
TI  - Different roles of N- and C- termini in the functional activity of FGF21.
AB  - Fibroblast growth factor 21 is a member of endocrine FGFs subfamily, along with
      FGF19 and FGF23. It is emerging as a novel regulator with beneficial effects on a
      variety of metabolic parameters, including glucose and lipid control. FGF21
      activity depends on membrane protein betaKlotho that physically complexes with
      various FGF receptors, thus conferring them the ability to bind FGF21 and
      activate downstream signaling pathways. FGF21, like other FGFs, folds to a beta
      trefoil-like core region, with disordered N- and C-termini. In order to
      investigate their role in the activity of FGF21, we have constructed a series of
      deletion mutants and tested them for their ability to (1) bind betaKlotho,
      analyzed by surface plasmon resonance spectroscopy (2) signal through MAPK
      phosphorylation and inhibit apoptosis in 3T3-L1/betaKlotho fibroblasts (3)
      stimulate GLUT1 mRNA upregulation and glucose uptake in 3T3-L1 adipocytes.
      Binding studies with betaKlotho revealed that the interaction with the co
      receptor involves the C-terminus, as progressive removal of amino acids from the
      carboxy end decreased affinity for betaKlotho. By contrast, removal of up to 17
      amino acids from the N-terminus had no effect on the interaction with betaKlotho.
      Terminal deletions had greater effect on function, as deletions of six amino
      acids from the amino-terminus and only four from the carboxy-terminus each
      significantly impacted activity (10-fold). Of the extreme terminal truncations,
      with no detectable activity, DeltaN17 acted as competitive antagonist while
      DeltaC20 did not. Our structure/function studies show that the C-terminus is
      important for betaKlotho interaction whereas the N-terminus likely interacts
      directly with FGF receptors.

PMID- 19117009
TI  - An shRNA silencing a non-toxic transgene reduces nutrient consumption and
      increases production of adenoviral vectors in a novel packaging cell.
AB  - During production of an adenoviral vector in a packaging cell, transgene is
      expressed concomitantly with the adenoviral gene. Depending on the protein
      encoded by the transgene, the yield of an adenoviral vector can be reduced or
      blocked as a result of transgene expression in the packaging cell. We tested the
      effect of a short hairpin RNA (shRNA) inhibiting the expression of a transgene
      encoding hIcon, a therapeutic molecule that selectively destroys pathological
      angiogenic blood vessels, on the yield of an adenoviral vector containing the
      transgene. The results showed that the yield of infectious adenoviral vector
      particles was increased about 10-fold in a novel packaging cell with stable
      production of an shRNA that can silence the transgene, as compared to the yield
      in standard packaging line, and the consumption of nutrient in the novel
      packaging cell line is decreased due to silence of adenoviral transgene
      expression. The study indicates that shRNA can increase the production of
      adenoviral vectors by silencing transgene and reducing nutrient consumption of
      the novel packaging cell. The use of shRNA silencing expression of transgenes
      encoding therapeutic molecules can reduce the time and cost of producing
      adenoviral vectors for clinical use.

PMID- 19117010
TI  - Critical size for O(2) dissociation by au nanoparticles.
AB  - Density functional theory calculations predict that the presence of low
      coordination Au atoms is not enough to dissociate O(2), that there is a common
      pathway for O(2) dissociation on Au nanoparticles and that there is critical size
      for Au nanoparticles to dissociate O(2) (see figure).Density functional theory
      calculations carried out for a series of Au nanoparticles as well as for extended
      systems containing low-coordinated sites show that the presence of low-coordinate
      Au atoms is not enough to dissociate O(2). Strong adsorption of molecular oxygen
      on Au nanoparticles is a necessary but not sufficient condition for O(2)
      dissociation, there is a common pathway for O(2) dissociation on these
      nanoparticles and there is critical size for Au nanoparticles to dissociate O(2).

PMID- 19117011
TI  - Estrogen receptor beta-mediated nuclear interaction between IRS-1 and Rad51
      inhibits homologous recombination directed DNA repair in medulloblastoma.
AB  - In medulloblastomas, which are highly malignant cerebellar tumors of the
      childhood genotoxic treatments such as cisplatin or gamma-irradiation are
      frequently associated with DNA damage, which often associates with unfaithful DNA
      repair, selection of new adaptations and possibly tumor recurrences. Therefore,
      better understanding of molecular mechanisms which control DNA repair fidelity
      upon DNA damage is a critical task. Here we demonstrate for the first time that
      estrogen receptor beta (ERbeta) can contribute to the development of genomic
      instability in medulloblastomas. Specifically, ERbeta was found highly expressed
      and active in mouse and human medulloblastoma cell lines. Nuclear ERbeta was also
      present in human medulloblastoma clinical samples. Expression of ERbeta coincided
      with nuclear translocation of insulin receptor substrate 1 (IRS-1), which was
      previously reported to interfere with the faithful component of DNA repair when
      translocated to the nucleus. We demonstrated that ERbeta and IRS-1 bind each
      other, and the interaction involves C-terminal domain of IRS-1 (aa 931-1233).
      Following cisplatin-induced DNA damage, nuclear IRS-1 localized at the sites of
      damaged DNA, and interacted with Rad51--an enzymatic component of homologous
      recombination directed DNA repair (HRR). In medulloblastoma cells, engineered to
      express HRR-DNA reporter plasmid, ER antagonist, ICI 182,780, or IRS mutant (931
      1233) significantly increased DNA repair fidelity. These data strongly suggest
      that both molecular and pharmacological interventions are capable of preventing
      ERbeta-mediated IRS-1 nuclear translocation, which in turn improves DNA repair
      fidelity and possibly counteracts accumulation of malignant mutations in actively
      growing medulloblastomas.

PMID- 19117012
TI  - Chaperone-mediated autophagy is defective in mucolipidosis type IV.
AB  - Mucolipidosis type IV (MLIV) is a lysosomal storage disorder caused by mutations
      in the MCOLN1 gene, a member of the transient receptor potential (TRP) cation
      channel gene family. The encoded protein, transient receptor potential mucolipin
      1 (TRPML1), has been localized to lysosomes and late endosomes but the pathogenic
      mechanism by which loss of TRPML1 leads to abnormal cellular storage and neuronal
      cell death is still poorly understood. Yeast two-hybrid and co
      immunoprecipitation (coIP) experiments identified interactions between TRPML1 and
      Hsc70 as well as TRPML1 and Hsp40. Hsc70 and Hsp40 are members of a molecular
      chaperone complex required for protein transport into the lysosome during
      chaperone-mediated autophagy (CMA). To determine the functional relevance of this
      interaction, we compared fibroblasts from MLIV patients to those from sex- and
      age-matched controls and show a defect in CMA in response to serum withdrawal.
      This defect in CMA was subsequently confirmed in purified lysosomes isolated from
      control and MLIV fibroblasts. We further show that the amount of lysosomal
      associated membrane protein type 2A (LAMP-2A) is reduced in lysosomal membranes
      of MLIV fibroblasts. As a result of decreased CMA, MLIV fibroblasts have
      increased levels of oxidized proteins compared to control fibroblasts. We
      hypothesize that TRPML1 may act as a docking site for intralysosomal Hsc70 (ly
      Hsc70) allowing it to more efficiently pull in substrates for CMA. It is also
      possible that TRPML1 channel activity may be required for CMA. Understanding the
      role of TRPML1 in CMA will undoubtedly help to characterize the pathogenesis of
      MLIV.

PMID- 19117013
TI  - Dystrophin glycoprotein complex-associated Gbetagamma subunits activate
      phosphatidylinositol-3-kinase/Akt signaling in skeletal muscle in a laminin
      dependent manner.
AB  - Previously, we showed that laminin-binding to the dystrophin glycoprotein complex
      (DGC) of skeletal muscle causes a heterotrimeric G-protein (Galphabetagamma) to
      bind, changing the activation state of the Gsalpha subunit. Others have shown
      that laminin-binding to the DGC also leads to Akt activation. Gbetagamma,
      released when Gsalpha is activated, is known to bind phosphatidylinositol-3
      kinase (PI3K), which activates Akt in other cells. Here, we investigate whether
      muscle Akt activation results from Gbetagamma, using immunoprecipitation and
      immunoblotting, and purified Gbetagamma. In the presence of laminin, PI3K-binding
      to the DGC increases and Akt becomes phosphorylated and activated (pAkt), and
      glycogen synthase kinase is phosphorylated. Antibodies, which specifically block
      laminin-binding to alpha-dystroglycan, prevent PI3K-binding to the DGC. Purified
      bovine brain Gbetagamma also caused PI3K and Akt activation. These results show
      that DGC-Gbetagamma is binding PI3K and activating pAkt in a laminin-dependent
      manner. Mdx mice, which have greatly diminished amounts of DGC proteins, display
      elevated pAkt signaling and increased expression of integrin beta1 compared to
      normal muscle. This integrin binds laminin, Gbetagamma, and PI3K. Collectively,
      these suggest that PI3K is an important target for the Gbetagamma, which normally
      binds to DGC syntrophin, and activates PI3K/Akt signaling. Disruption of the DGC
      in mdx mouse is causing dis-regulation of the laminin-DGC-Gbetagamma-PI3K-Akt
      signaling and is likely to be important to the pathogenesis of muscular
      dystrophy. Upregulating integrin beta1 expression and activating the PI3K/Akt
      pathway in muscular dystrophy may partially compensate for the loss of the DGC.
      The results suggest new therapeutic approaches to muscle disease.

PMID- 19117015
TI  - Factors associated with detection failure and false-negative sentinel node biopsy
      findings in gastric cancer: results of prospective single center trials.
AB  - BACKGROUND AND OBJECTIVES: The factors associated with successful sentinel node
      biopsy (SNB) are limited in gastric cancer despite a wide range of sensitivities
      reported. This study was performed to identify the factors associated with
      detection failure and SNB false-negativity in gastric cancer. METHODS: SNB was
      performed on 156 gastric cancer patients from May 2002 to April 2007 at the
      Korean National Cancer Center during three consecutive prospective trials.
      Indications for SNB were determined preoperatively in cT1-2N0 patients. Dissected
      SNs and non-SNs after D2 lymphadenectomy were pathologically evaluated for
      metastasis. Clinical, pathological, and technical factors were analyzed for
      detection failure and false-negativity. RESULTS: SNs were detected in 147
      patients (94.2%) and the median number of SNs detected per patient was 3 (1-12).
      Twenty-five of 37 with nodal metastasis were diagnosed by SNB (sensitivity,
      67.6%). Surgeon's inexperience (<or=30 procedures) and a male patient gender were
      significantly associated with detection failure (P = 0.014 and 0.031,
      respectively). A small number of SNs (<or= 3) was found to be significantly
      associated with false-negativity (P = 0.027). CONCLUSIONS: SNB requires
      experience for successful detection and should be performed cautiously in male
      patients. Harvesting of more than three SNs is warranted to reduce false
      negatives when diagnosing nodal metastasis.

PMID- 19117014
TI  - Role of TLS DNA polymerases eta and kappa in processing naturally occurring
      structured DNA in human cells.
AB  - Accurate DNA replication during S-phase is fundamental to maintain genome
      integrity. During this critical process, replication forks frequently encounter
      obstacles that impede their progression. While the regulatory pathways which act
      in response to exogenous replication stress are beginning to emerge, the
      mechanisms by which fork integrity is maintained at naturally occurring
      endogenous replication-impeding sequences remains obscure. Notably, little is
      known about how cells replicate through special chromosomal regions containing
      structured non-B DNA, for example, G4 quartets, known to hamper fork progression
      or trigger chromosomal rearrangements. Here, we have investigated the role in
      this process of the human translesion synthesis (TLS) DNA polymerases of the Y
      family (pol eta, pol iota, and pol kappa), specialized enzymes known to
      synthesize DNA through DNA damage. We show that depletion by RNA interference of
      expression of the genes for Pol eta or Pol kappa, but not Pol iota, sensitizes
      U2OS cells treated with the G4-tetraplex interactive compound telomestatin and
      triggers double-strand breaks in HeLa cells harboring multiple copies of a G-rich
      sequence from the promoter region of the human c-MYC gene, chromosomally
      integrated as a transgene. Moreover, we found that downregulation of Pol kappa
      only raises the level of DSB in HeLa cells containing either one of two breakage
      hotspot structured DNA sequences in the chromosome, the major break region (Mbr)
      of BCL-2 gene and the GA rich region from the far right-hand end of the genome of
      the Kaposi Sarcoma associated Herpesvirus. These data suggest that naturally
      occurring DNA structures are physiological substrates of both pol eta and pol
      kappa. We discuss these data in the light of their downregulation in human
      cancers.

PMID- 19117016
TI  - Vascular endothelial growth factor-C and -D expression correlates with lymph node
      micrometastasis in pN0 early gastric cancer.
AB  - BACKGROUND AND OBJECTIVES: Vascular endothelial growth factors (VEGF)-C and -D
      play an important role in lymphangiogenesis, and the expressions of these factors
      are related to lymphatic invasion and lymph node metastasis in various malignant
      neoplasms. The present study investigates the expression of VEGF-C and -D in
      early gastric cancer and analyzes its relationship to lymph node micrometastasis
      determined by reverse transcription-polymerase chain reaction (RT-PCR). METHODS:
      We examined 1,828 lymph nodes obtained from 80 patients with node-negative early
      gastric cancer. All dissected lymph nodes were examined by RT-PCR for CEA mRNA in
      addition to hematoxylin-eosin staining. The resected primary specimens were
      immunostained using anti-VEGF-C and -D polyclonal antibodies. RESULTS: The
      incidence of lymph node micrometastasis determined by RT-PCR was 23.8% (19/80).
      The high expression of VEGF-C and -D was found in 27.5% (22/80) and in 21.3%
      (17/80), respectively. The expression of VEGF-C and -D was closely related to
      lymph node micrometastasis (P = 0.0390 and 0.0213, respectively). CONCLUSIONS: We
      demonstrated a close relationship between micrometastasis and VEGF-C and -D
      expression of the primary tumor. Thus, levels of VEGF-C and -D expression might
      be useful for predicting micrometastasis in patients with early gastric cancer.

PMID- 19117017
TI  - Prevalence and risk of asthma symptoms among firefighters in Sao Paulo, Brazil: a
      population-based study.
AB  - The firefighters are at increased risk of respiratory disease as a result of
      exposure to smoke and dust. The aim of this study was to determine the prevalence
      and risk associated with respiratory symptoms among city firefighters in Sao
      Paulo, Brazil. METHODS: A cross-sectional study utilizing the European Community
      Respiratory Health Survey (ECRHS) questionnaire was administered to firefighters
      and police officers, in order to evaluate their respiratory symptoms. RESULTS:
      Complete respiratory data were obtained from 1,235 firefighters and 1,839 police
      officers. Among the firefighters, there were 55.5% never-smokers, 22.4% current
      smokers and 18.2% former smokers (P < 0.05). Among the police officers, there
      were 63.4%, 18.6%, and 9.6% who were never-smokers, current smokers and former
      smokers (P < 0.05), respectively. Compared to police, firefighters experienced an
      increase in wheezing [OR = 1.63 (95% CI: 1.43-1.87)], wheezing with
      breathlessness [OR = 1.34 (95% CI: 1.10-1.64)], wheezing without a cold [OR =
      1.60 (95% CI: 1.32-1.95)], waking with tightness in the chest [OR = 1.20 (95% CI:
      1.02-1.42)], and rhinitis [OR = 1.12 (95% CI: 1.03-1.22)]. The prevalence of
      adult-onset asthma in never-smokers was 9.3% and 6.7% for firefighters and police
      officers [OR = 1.23 (95% CI: 1.01-1.56)]. An independent association was observed
      between years employed, smoking, history of rhinitis, and work as a firefighter
      and respiratory and nasal symptoms. We observed a high prevalence of asthma-like
      symptoms in firefighters who presented respiratory symptoms beginning immediately
      after firefighting. CONCLUSION: These results suggest that the prevalence of
      respiratory symptoms and asthma in firefighters is higher than those in police
      officers. Work-as a firefighter, rhinitis and years employed were risk factors
      for respiratory symptoms of asthma.

PMID- 19117018
TI  - Clinicopathologic characteristics and outcomes of gastric cancers with the MSI-H
      phenotype.
AB  - OBJECTIVES: We examined the correlation between microsatellite instability (MSI)
      status and the clinicopathological features and prognostic value in gastric
      cancer and compared the efficacy of immunohistochemical staining for hMLH1 and
      hMSH2 with a polymerase chain reaction (PCR)-based test. METHODS: MSI status was
      examined in 328 consecutive gastric adenocarcinomas using tissue preserved in
      paraffin blocks. DNA extracted from tumor sections and the corresponding normal
      tissue was analyzed using PCR at the five microsatellite loci recommended by the
      National Cancer Institute (NCI). Immunohistochemical staining for hMLH1 and hMSH2
      was performed and the results were compared with the MSI status measured using
      PCR. The relationship of the clinicopathologic variables to MSI status was
      analyzed. RESULTS: Of the gastric cancers, 8.2% (n = 27) contained MSI-H and this
      was associated with older age (>70 years), distal tumor location, tumor size, and
      intestinal subtype. Lymphatic and vascular invasion were associated with the
      disease-free survival. On immunohistochemical staining, the loss of expression of
      hMLH1 or hMSH2 was observed in 11% (n = 36). The sensitivity, specificity,
      positive predictive value, negative predictive value, and accuracy of
      immunohistochemical staining were 63.0%, 93.7%, 47.2%, 96.6%, and 91.2%,
      respectively. CONCLUSIONS: Gastric cancers with MSI-H have specific
      clinicopathologic characteristics, such as older age at diagnosis, distal tumor
      location, increased tumor size, and intestinal histologic type. However,
      immunohistochemical staining for hMLH1 and hMSH2 is not as accurate as the PCR
      based MSI test.

PMID- 19117019
TI  - Comparative protective effect of N-acetyl cysteine and tetramethylpyrazine in
      rats with gentamicin nephrotoxicity.
AB  - Gentamicin (GM) is used against serious and life-threatening infections, but its
      use is limited by the occurrence of nephrotoxicity, which involves the generation
      of free radicals. In this work we tested the effect of a compound with
      antioxidant properties, tertamethylpyrazine (TMP), a major constituent of the
      Chinese medicinal plant Lingusticum wallichi, on GM-induced nephrotoxicity, and
      compared it with an established anti-oxidant compound N-acetyl cysteine (NAC).
      Six groups of rats were studied: (1) control, treated orally (p.o.) and
      intraperitoneally (i.p.) with saline; (2) treated i.p. with GM (80 mg kg(-1) per
      day for 6 days); (3) TMP, given p.o. (100 mg kg(-1) per day for 10 days) + GM
      (same dose as above during the last 6 days); (4) NAC, given i.p. (500 mg kg(-1)
      per day for 10 days) + GM as above; (5) TMP (100 mg kg(-1) per day for 10 days) +
      saline; (6) NAC (500 mg kg(-1) per day for 10 days) + saline. GM nephrotoxicity
      was characterized by reduced creatinine clearance, increased creatinine and urea
      concentrations in plasma, increased urinary excretion of N-acetyl-beta-d
      glucosaminidase (NAG) and total protein. These functional and structural
      alterations were prevented or ameliorated by NAC treatment, while TMP had only a
      slight mitigating effect that was less marked than that produced by NAC. The
      concentration of GM in the renal cortex of the rats given GM + NAC (but not TMP)
      was lower than that found in rats treated with GM alone by about 25%. The
      mechanism by which NAC and, to a lesser extent TMP, protected against GM-induced
      nephrotoxicity may be related, at least in part, to the decrease in oxidative
      stress in renal cortex.

PMID- 19117020
TI  - Off-pump, minimally invasive and robotic coronary revascularization yield
      improved outcomes over traditional on-pump CABG.
AB  - Coronary artery disease is a global health concern, with increasing morbidity and
      mortality. Surgical coronary artery bypass grafting has been performed on
      cardiopulmonary bypass for nearly four decades, with excellent long-term
      durability. Beating-heart coronary surgery has been increasing in frequency in an
      attempt to decrease cardiopulmonary bypass-related morbidity. Furthermore, with
      increasing expertise and technology, minimally invasive and robotic techniques
      have been developed to enhance post-operative recovery, patient satisfaction and
      cosmesis. Several clinical trials have demonstrated decreased morbidity and more
      rapid recovery following off-pump, minimally invasive and robotic procedures when
      compared to on-pump coronary artery bypass grafts (CABGs). An equivalent extent
      of revascularization and medium-term anastomotic patency has been demonstrated
      among all approaches. Furthermore, for a large number of patients who do not have
      anatomy amenable to traditional coronary revascularization, adjunctive molecular
      therapies may provide alternative myocardial micro-revascularization.

PMID- 19117021
TI  - Jakking up tumor registry reporting of the myeloproliferative neoplasms.

PMID- 19117022
TI  - The influence of genetic variations in HHEX gene on insulin metabolism in the
      German MESYBEPO cohort.
AB  - BACKGROUND: In the present study, we aimed to validate the type 2 diabetes (T2DM)
      susceptibility alleles identified in the first genome-wide association study in
      the hematopoietically expressed homeobox protein (HHEX) gene region (rs1111875
      and rs7923837). Furthermore, we investigated quantitative metabolic risk
      phenotypes of these two variants for association with three key components of the
      insulin metabolism: insulin secretion, insulin sensitivity and insulin
      degradation. METHODS: Two HHEX polymorphisms were genotyped in 1026 subjects from
      the German MESYBEPO cohort. Complete OGTT data were available for a subset of 420
      with normal glucose tolerance (NGT), 282 with impaired glucose tolerance/impaired
      fasting glucose (IGT/IFG) and 146 diabetic subjects. RESULTS: We validated
      association of both HHEX polymorphisms with T2DM. In the non-diabetic subcohort
      including NGT and IFG/IGT subjects, the risk alleles of rs7923837 and rs1111875
      were significantly associated with decreased first and second phases of insulin
      secretion and lower insulinogenic index after oral glucose loading. In healthy,
      normal glucose-tolerant subjects, the same association of HHEX SNP rs1111875 with
      OGTT-derived phases of insulin secretion were detectable, however, rs7923837 was
      only weakly associated with reduced insulinogenic index. For both polymorphisms,
      no significant correlations with insulin sensitivity were obtained. Reduced
      insulin clearance was also observed in heterozygous carriers of rs1111875.
      CONCLUSIONS: We validated the association of polymorphisms of the HHEX gene with
      T2DM in the MESYBEPO cohort. Importantly, variations within the HHEX gene
      conferred the impaired insulin secretion and changes of insulin degradation but
      no alteration in insulin sensitivity in carriers of risk alleles.

PMID- 19117023
TI  - Assembly properties of the Bacillus subtilis actin, MreB.
AB  - The bacterial actin MreB has been implicated in a variety of cellular roles
      including cell shape determination, cell wall synthesis, chromosome condensation
      and segregation, and the establishment and maintenance of cell polarity. Toward
      elucidating a clearer understanding of how MreB functions inside the bacterial
      cell, we investigated biochemically the polymerization of MreB from Bacillus
      subtilis. Light scattering and sedimentation assays revealed pH-, ionic-,
      cationic-, and temperature-dependent behavior. B. subtilis MreB polymerizes in
      the presence of millimolar divalent cations in a protein concentration-dependent
      manner. Polymerization is favored by decreasing pH and inhibited by monovalent
      salts and low temperatures. Although B. subtilis MreB binds and hydrolyzes both
      ATP and GTP, it does not require a bound nucleotide for assembly and polymerizes
      indistinguishably regardless of the nucleotide species bound, with a critical
      concentration of approximately 900 nM. A number of the presently reported
      properties of B. subtilis MreB differ significantly from those of T. maritima
      MreB1 (Bean and Amann [2008]: Biochemistry 47: 826-835), including the nucleotide
      requirements and temperature and ionic effects on polymerization state. These
      observations collectively suggest that additional factors interact with MreB to
      account for its complex dynamic behavior in cells.

PMID- 19117024
TI  - Intracellular signal transduction pathways in the regulation of fowl sperm
      motility: evidence for the involvement of phosphatidylinositol 3-kinase (PI3-K)
      cascade.
AB  - The possible role of PI3-K in the reversible temperature-dependent immobilization
      of fowl sperm motility was investigated by using PI3-K inhibitor (LY294002) and
      its inactive analogue (LY303511). The existence of the PI3-K in fowl spermatozoa
      was also confirmed by Western blotting analysis. Fowl sperm motility in TES/NaCl
      buffer remained negligible at the avian body temperature of 40 degrees C but was
      maintained vigorously when the temperature was decreased to 30 degrees C. At 30
      degrees C, no stimulation or inhibition of motility was observed after the
      addition of 2 mM CaCl2 and 10 microM LY294002 or LY303511: around 70-80% of
      spermatozoa remained motile. In contrast, at 40 degrees C, the motility of
      spermatozoa was activated immediately after the addition of Ca(2+), but the
      subsequent addition of LY294002 inhibited the motility again. The addition of
      LY303511 did not appreciably affect the Ca(2+)-supplemented sperm motility, which
      was maintained for at least 15 min. The ATP concentrations of spermatozoa after
      the addition of LY294002 + Ca(2+) or LY303511 + Ca(2+) were almost the same
      values compared with those of Ca(2+) alone at 40 degrees C, suggesting that the
      addition of LY294002 was not simply affecting membrane damage or inhibiting
      energy production in the spermatozoa, but may be acting on some part of the
      motility-regulating cascade. Immunoblotting of sperm extract using an antibody to
      PI3-K revealed a major cross-reacting protein of 85 kDa, which corresponds to the
      molecular weight of the subunit of PI3-K. These results suggest that PI3-K may be
      positively involved in the calcium-regulated maintenance of flagellar movement of
      fowl spermatozoa at 40 degrees C.

PMID- 19117025
TI  - Consideration of hereditary nonpolyposis colorectal cancer in BRCA mutation
      negative familial ovarian cancers.
AB  - BACKGROUND: Inherited mutations account for approximately 10% of all epithelial
      ovarian cancers. Breast cancer (BRCA1 and BRACA2) gene mutations are responsible
      for up to 85% of inherited breast and/or ovarian cancer. Another condition that
      has been associated with ovarian cancer is hereditary nonpolyposis colorectal
      cancer syndrome (HNPCC), which carries a lifetime risk of up to 13% for ovarian
      cancer. The objective of this study was to determine the incidence of HNPCC
      related gene mutations in patients with familial ovarian cancer who previously
      tested negative for BRCA1 and BRCA2 gene mutations. METHODS: Seventy-seven
      probands were identified who had familial ovarian cancer and negative BRCA gene
      mutation testing. Their pedigrees were analyzed for HNPCC syndrome. DNA samples
      underwent gene sequencing and Southern blot analysis for mutations in the 3 most
      common HNPCC-associated genes: mutL homolog 1 (MLH1) and mutS homolog 2 (MSH2)
      with reflex testing for MSH6 if tests for the first 2 genes were negative.
      RESULTS: None of the probands met Amsterdam criteria for the clinical diagnosis
      of HNPCC. DNA testing revealed 2 patients (2.6%) with deleterious mutations in
      the MSH2 gene. An additional 8 patients (10.4%) had substitutions in either the
      MLH1 gene or the MSH2 gene that were classified as variants of uncertain
      significance. If Amsterdam criteria were expanded to include ovarian cancer, then
      15 of 77 patients (19.5%) would have met these expanded criteria. One deleterious
      mutation was noted in this group, yielding a mutation incidence of 6.7%. This
      percentage may be even higher if any of the identified variants of uncertain
      significance are confirmed to be deleterious. CONCLUSIONS: HNPCC should be
      considered when evaluating patients with suspected hereditary ovarian cancer who
      have had negative BRCA mutation testing.

PMID- 19117026
TI  - Mating modifies apoptosis pattern in epithelial cells of the rat uterus.
AB  - Estrous cycle in mammals includes marked epithelial changes in reproductive
      tract, regulated by sex steroid hormones. In the present work we studied the
      activation of caspases and apoptotic pattern in uterine epithelial cells during
      proestrus and estrus, and the effect of mating in this process. In addition, we
      investigated the role of seminal vesicle secretions on apoptosis of uterine
      epithelia. Apoptotic index was evaluated by TUNEL assay, caspases-8, -9, and -3
      activation was detected by Western blot and active caspase-3 expression was
      detected by immunohistochemistry. Our results show that mating during proestrus
      and estrus transition induced changes in the apoptotic pattern of uterine luminal
      epithelium during estrus, characterized by a delay in the onset of apoptosis as
      compared with that observed in nonmated rats. No differences in the apoptotic
      pattern in the glandular epithelium between mated and nonmated rats were
      observed. Seminal vesicle secretions inhibited luminal epithelium apoptosis,
      while no changes in glandular epithelium apoptosis were observed. We also
      demonstrate that activation of caspases-8, -9, and -3 occurred in both mated and
      nonmated rats. Active caspase-3 was detected in the luminal and glandular
      epithelium in both nonmated and mated rats. The overall results indicate that
      mating delays but does not prevent the cellular death of the rat uterine luminal
      epithelium and seminal vesicle secretions are involved in this delay. Finally,
      the activation of both the mitochondrial and the membrane receptor pathways of
      cell death are implicated in the molecular mechanism of uterine apoptosis.

PMID- 19117027
TI  - The roles of obesity and gender on the relationship between metabolic risk
      factors and non-alcoholic fatty liver disease in Koreans.
AB  - BACKGROUND: The effect of gender and weight status on the association between
      metabolic risk factors and NAFLD has not been well established. This study aimed
      to assess the relationships among obesity, gender, metabolic risk factors, and
      non-alcoholic fatty liver disease (NAFLD) in Korean adults. METHODS: Abdominal
      ultrasounds, anthropometric measurements, and biochemical tests were performed on
      13,768 Korean adults (7,313 men and 6,455 women) recruited from a health
      promotion centre between 2005 and 2006. RESULTS: Of 13,768 subjects, 25% were
      diagnosed with NAFLD. Weight status (obesity vs non-obesity, odds ratio (OR) 4.4
      9.7) and gender (women vs men, OR 0.6) were associated with NAFLD after adjusting
      for age, metabolic risk factors (high blood pressure, high glucose, high TG, low
      HDL, high LDL, and high uric acid), and gamma-glutamyl transferase (gammaGT). For
      subjects with any one risk factor, the OR (95% CI) for mild fatty liver was 27
      (19.3-37.8) in men and 7.9 (6.1-10.2) in women who were obese compared to non
      obese individuals having no risk factors. The ORs in men and women who were not
      obese were 4.7 (3.9-5.6) and 2.5 (2.2-3.0), respectively. The sensitivity and
      specificity for NAFLD with any one risk factor without obesity was 90-91 and 32
      49%, respectively; any one risk factor combined with obesity changed the
      sensitivity and specificity to 64-67 and 77-85%, respectively. CONCLUSIONS:
      Gender and weight status appear to modify the relationship between metabolic risk
      factors and NAFLD.

PMID- 19117028
TI  - Proteopedia.Org: a scientific "Wiki" bridging the rift between 3D structure and
      function of biomacromolecules.

PMID- 19117029
TI  - NMR evidence of charge-dependent interaction between various PND V3 and CCR5 N
      terminal peptides.
AB  - The third variable (V3) loop is an important region of glycoprotein 120 (gp120)
      for many biological processes, as it contains the highly conserved GPGR sequence
      and it represents the binding site for human immunodeficiency virus 1 (HIV-1)
      antibodies and for CCR5 and CXCR4 host cell coreceptors. The interaction of the
      principal neutralizing determinant (PND) V3 with the chemokine receptor CCR5 N
      terminal region has been reported to be crucial for HIV-1 infection. The goal of
      this study is to characterize the solution structures of three HIV-1 gp120 V3
      subtype B peptides and their interaction with a nonsulfated N-terminal CCR5
      peptide. NMR titration experiments revealed that the CCR5Nt-PND V3 interaction is
      dependent on the number of the positively charged V3 residues, which is in
      agreement with the observation that increase in positive charge in the V3
      sequence correlates with the augmentation of the interaction. As expected for
      free peptides in solution, the peptides representing the PND V3 region of gp120
      exhibit conformational flexibility, but they also exhibit a large number of NOEs
      which allowed convergence to a dominant conformation. The PND V3 peptides retain
      the U-turn conformation observed in the crystal structures of gp120 complexes
      independently of CCR5 presence. The interaction of different regions of the
      CCR5Nt peptide is gradually increasing proportionally to the positive charge
      increase in the V3 peptides. The data demonstrate that the PND V3 and CCR5Nt
      peptide sequences have propensities for interaction even in the absence of
      sulfated tyrosines and that their binding and selectivity is determined by simple
      electrostatic attraction mechanisms.

PMID- 19117030
TI  - Helix-coil energetics for helix formers and breakers reflect context and
      temperature: mutants of helically robust, guest-sensitive homopeptide hosts.
AB  - The natural amino acids are primarily helix breakers at the low assignment
      temperatures characteristic of many studies, but recent genomic analyses of
      thermophilic proteins suggest that at high temperatures, some breakers may become
      strong helix formers. Moreover, the breaker/former inventory has not been
      previously characterized at the physiologically relevant temperature of 37
      degrees C. The versatility of 13C==O NMR chemical shifts as helicity reporters
      allows construction of two mutant peptide series, tailored to expand the range of
      temperature assignments for helical propensities and derived from the core hosts
      tL-Ala9XxxAla9-tL and tL-AlaNva4XxxNva4Ala9-tL, Nva=norvaline. For three limiting
      guests Xxx, the helix former Nva and the breakers Gly and Pro, we report wXxx[T]
      assignments at seven temperatures from 2 to 80 degrees C, validating our
      reasoning and paving the way for assignment of a definitive wXxx[T] data-base.

PMID- 19117032
TI  - Nip2/centrobin may be a substrate of Nek2 that is required for proper spindle
      assembly during mitosis in early mouse embryos.
AB  - Nek2 is a mitotic kinase with multiple cellular functions involving
      phosphorylation of diverse substrates. Suppression of Nek2 in early mouse embryos
      has been shown to arrest development at the 4-cell stage with defects in mitotic
      spindle assembly as well as in interphase nuclear morphology. In the present
      study, we suppressed expression of two Nek2 centrosomal substrates, Nip2 and C
      Nap1, in early mouse embryos. The development of the Nip2-suppressed embryo was
      arrested at the 4-cell stage with mitotic defects in the blastomeres. In
      contrast, C-Nap1 suppression did not produce a visible phenotype. The phenotypic
      similarities of the Nip2- and Nek2-suppressed embryos suggest that Nip2 may be a
      substrate of Nek2 that is required for mitotic spindle assembly in early mouse
      embryos.

PMID- 19117031
TI  - Evaluation of binding selectivities and affinities of platinum-based quadruplex
      interactive complexes by electrospray ionization mass spectrometry.
AB  - The quadruplex binding affinities and selectivities of two large pi-surface
      Pt(II) phenanthroimidazole complexes, as well as a smaller pi-surface platinum
      bipyridine complex and a larger Ru(II) complex, were evaluated by electrospray
      ionization mass spectrometry. Circular dichroism (CD) spectroscopy was used to
      determine the structures of various quadruplexes and to study the thermal
      denaturation of the quadruplexes in the absence and presence of the metal
      complexes. In addition, chemical probe reactions with glyoxal were used to
      monitor the changes in the quadruplex conformation because of association with
      the complexes. The platinum phenanthroimidazole complexes show increased affinity
      for several of the quadruplexes with elongated loops between guanine repeats.
      Quadruplexes with shorter loops exhibited insubstantial binding to the transition
      metal complexes. Similarly binding to duplex and single strand oligonucleotides
      was low overall. Although the ruthenium-based metal complex showed somewhat
      enhanced quadruplex binding, the Pt(II) complexes had higher quadruplex
      affinities and selectivities that are attributed to their square planar
      geometries. The chemical probe reactions using glyoxal indicated increased
      reactivity when the platinum phenanthroimidazole complexes were bound to the
      quadruplexes, thus suggesting a conformational change that alters guanine
      accessibility.

PMID- 19117033
TI  - Prevention of postoperative hypocalcemia with routine oral calcium and vitamin D
      supplements in patients with differentiated papillary thyroid carcinoma
      undergoing total thyroidectomy plus central neck dissection.
AB  - BACKGROUND: Routine oral calcium and vitamin D supplementation may prevent
      hypocalcemic crisis, but its efficacy has not been studied in patients undergoing
      thyroidectomy plus central neck dissection (CND). The authors therefore
      prospectively evaluated the clinical usefulness of routine oral calcium and
      vitamin D supplementation for prevention of hypocalcemia after total
      thyroidectomy and CND. METHODS: Of 197 patients with differentiated papillary
      thyroid carcinoma, 49 underwent total thyroidectomy alone, and 148 underwent
      total thyroidectomy plus CND. The latter were randomized to oral calcium (3
      g/day) plus vitamin D (1 mg/day) (Group A, n=49), calcium alone (Group B, n=49),
      or no supplements (Group C, n=50). Hypocalcemic symptoms, serum calcium, and
      parathyroid hormone (PTH) levels were compared among the groups. RESULTS: Group C
      had significantly higher incidences of symptomatic (26.0% vs 6.1%; P<.015) and
      laboratory (44.0% vs 14.3%; P<.015) hypocalcemia than the group without CND. The
      incidences of symptomatic and laboratory hypocalcemia were significantly
      decreased in Groups A (2.0% and 8.2%, respectively) and B (12.2% and 24.5%,
      respectively) (P<.05). Serum calcium levels decreased in most patients after
      surgery, but recovered earliest in Group A. Hypercalcemia and PTH inhibition did
      not occur in gs A and B. CONCLUSIONS: Compared with total thyroidectomy alone,
      CND significantly increases the rate of postoperative hypocalcemia, which can be
      prevented by routine postoperative supplementation with oral calcium and vitamin
      D.

PMID- 19117034
TI  - Chemoimmunotherapy may overcome the adverse prognostic significance of 11q
      deletion in previously untreated patients with chronic lymphocytic leukemia.
AB  - BACKGROUND: An 11q22 deletion is considered an independent factor predicting poor
      survival in chronic lymphocytic leukemia (CLL). METHODS: We searched the
      electronic CLL database for consecutive patients who presented to the M. D.
      Anderson Cancer Center Department of Leukemia from October 2003 to April 2007
      with untreated CLL and who had an 11q22 deletion, detected by fluorescence in
      situ hybridization (FISH) analysis of bone marrow samples. FISH analysis was
      performed using the following probes: trisomy 12 (12p11.1-q11), TP53 (17p13.1),
      ATM (11q22.3), LAMP1 (13q34), and D13S319 loci (13q14.3). RESULTS: Sixty-nine
      patients with untreated CLL with an 11q22 deletion were identified. The median
      patient age was 59 years (range, 26-81 years); 80% were men, 53% had Zubrod
      performance status>0, and 13% had Rai stage III to IV disease. Lymphadenopathy
      (massive), splenomegaly, anemia, and thrombocytopenia were present in 96% (12%),
      19%, 9%, and 4%, respectively. In addition, 62% of patients had deletions in 13q,
      and 3% had trisomy 12. Forty patients required therapy for progressive disease.
      The overall response rates for FCR (fludarabine, cyclophosphamide, and
      rituximab), CFAR (FCR plus alemtuzumab), and rituximab plus granulocyte
      macrophage colony-stimulating factor were 100%, 100%, and 33%, respectively. The
      11q22 deletion was undetectable in 25 of 27 patients monitored after treatment
      using FISH analysis. The median follow-up was 17 months. At 1 and 3 years, the
      survival rates were 97% and 91%, respectively, and the relapse-free survival
      rates were 100% and 77%, respectively. CONCLUSIONS: CLL with an 11q22 deletion
      was associated with high rates of response, survival, and relapse-free survival
      when treated with chemoimmunotherapy.

PMID- 19117035
TI  - Galactomannan serves as a surrogate endpoint for outcome of pulmonary invasive
      aspergillosis in neutropenic hematology patients.
AB  - BACKGROUND: A noninvasive, objective, reproducible, and quantitative Aspergillus
      specific surrogate marker is needed for a more accurate assessment of the outcome
      of invasive aspergillosis (IA) in patients with a hematologic disorder. The
      quantitative serum galactomannan index (GMI) assay seems to fulfill the
      requirements of surrogacy for outcome evaluation. METHODS: Kappa statistics were
      used to determine the strength of correlation between GMI outcome and clinical
      outcome (survival or death), autopsy data, and response outcome of IA in 70
      adults with prolonged neutropenia. All patients underwent serial GMI monitoring
      until discharge or death. RESULTS: The overall correlation between GMI and
      clinical outcome was good at 6 weeks (kappa=0.5882; 95% confidence interval [95%
      CI], 0.4023-0.7741) and was excellent at 12 weeks (kappa=0.8857; 95% CI, 0.7766
      0.9948). Concordance with autopsy findings was perfect (kappa=1). At 6 weeks, the
      correlation between GMI and response outcome (favorable or unfavorable) was
      excellent (kappa=0.7523; 95% CI, 0.5803-0.9243). Survival was significantly
      better in patients who became GMI-negative (P<.0001). CONCLUSIONS: In neutropenic
      patients with seropositive IA, serum galactomannan index outcome strongly
      correlates with survival, autopsy findings, and response outcome. This finding
      may have implications for patient management and for clinical trial design.

PMID- 19117036
TI  - Cloning, characterization and expression of zvep, a novel vitelline envelope
      specific gene in the zebrafish ovary.
AB  - The egg envelope is a specialized extracellular matrix that surrounds and
      protects the oocyte and plays significant roles in animal reproductive and
      developmental processes. Using the NCBI digital differential display program we
      identified an EST sequence (XM_001340234.1) acquired from zebrafish ovary cDNA
      libraries in GeneBank. The full-length cDNA of this transcript was obtained by
      3'and 5' RACE and further confirmed by PCR and sequencing. The full-length cDNA
      of the novel gene is 2,720 bp and encodes a protein of 761 amino acids. RT-PCR
      and Western blot analysis showed its expression in ovary and brain but not in
      other tissues. In situ hybridization demonstrates that the mRNA is transcribed in
      ooplasm of stage I, II, and III oocytes. Interestingly, immunohistochemistry on
      zebrafish ovarian sections showed that protein expression in the vitelline
      envelope was located to two thin positive lines in the stage III oocytes. These
      ovarian expression patterns show that this is a new component of the vitelline
      envelope that is synthesized during early developing oocytes. This protein was
      named ZVEP (zebrafish vitelline envelope protein) and it did not have any
      homology with other known vitelline envelope genes. Thus, we found that zvep is a
      novel gene related to the vitelline envelope in zebrafish.

PMID- 19117037
TI  - Roles of protein kinase C isotypes during seawater-versus cAMP-induced oocyte
      maturation in a marine worm.
AB  - Based on immunoblotting analyses using phospho-specific antibodies, follicle-free
      oocytes of the marine nemertean worm Cerebratulus sp. activate protein kinase C
      (PKC) when induced to mature by either seawater (SW) or cAMP-elevating drugs. In
      SW-stimulated oocytes, the onset of maturation (=germinal vesicle breakdown,
      "GVBD") can be inhibited by broadly acting PKC antagonists such as
      bisindoylmaleimide (BIM)-I or BIM-IX. Conversely, co-treatment with SW solutions
      of BIM-I or BIM-IX plus a cAMP elevator (forskolin, serotonin, or a
      phosphodiesterase inhibitor) restores GVBD, indicating that the blockage of SW
      induced GVBD by PKC antagonists is not simply due to oocyte morbidity and that
      such inhibition is somehow reversible by cAMP signaling. In tests to determine
      which specific PKC may be involved in regulating GVBD, immunoblots fail to
      provide strong evidence for the presence of conventional or novel PKCs, which are
      characteristically activated by 12-O-tetradecanoylphorbol-13-acetate (TPA).
      Moreover, inhibitors of TPA-sensitive PKCs do not prevent SW-induced GVBD, and
      TPA itself serves to downregulate, rather than stimulate, GVBD. Alternatively,
      maturing oocytes apparently possess phosphorylated forms of TPA-insensitive
      isotypes, including an approximately 67-kDa atypical PKC and an approximately 130
      kDa PKC-related kinase (PRK). Accordingly, inhibitors of atypical PKC signaling
      block SW-but not cAMP-induced GVBD, collectively suggesting that instead of
      depending on a conventional or novel isotype, SW-induced GVBD may require
      atypical PKC and/or PRK. In addition, such findings provide further support for
      the view that GVBD in nemertean oocytes can be achieved via multiple mechanisms,
      with SW triggering different signaling pathways than are stimulated in the
      presence of cAMP-elevating drugs.

PMID- 19117038
TI  - Continous improvement of TNM staging system for bladder cancer.

PMID- 19117039
TI  - Twenty-four-month postradiation prostate biopsies are strongly predictive of 7
      year disease-free survival: results from a Canadian randomized trial.
AB  - BACKGROUND: The objective of this study was to evaluate the predictive value of
      prostate biopsies that were obtained 24 months after the completion of
      radiotherapy (RT) with respect to disease-free survival (DFS) in a randomized
      trial that compared 3 months versus 8 months of neoadjuvant hormone therapy
      before conventional dose external RT. METHODS: From February 1995 to June 2001,
      378 men were randomized to receive either 3 months or 8 months of combined
      flutamide and goserelin before they received 66 Gray of RT at 4 participating
      centers. By risk group, 26% of patients were categorized as low risk, 43% were
      categorized as intermediate risk, and 31% were categorized as high risk. The 2
      treatment arms were balanced in terms of age, Gleason score, clinical tumor
      classification, risk group, and presenting prostate-specific antigen level. The
      median follow-up for the patients who remained alive was 6.6 years (range, 1.6
      10.1 years). Of 361 evaluable patients, 290 patients remained alive. Post-RT
      prostate biopsies were performed between 24 and 30 months after the completion of
      RT in 3 of the 4 centers. Biopsies that had residual tumor with severe treatment
      effect were considered indeterminate, and biopsies that had minimal or no
      treatment effect were considered positive. RESULTS: The 5-year rate of actuarial
      freedom from any failure for the 3-month arm versus the 8-month arm was 72%
      versus 75% (P = .18). The DFS for patients who had negative and indeterminate
      biopsies was similar. Two-year post-treatment biopsy status was a strong
      predictor of 5-year DFS rate (82% and 83% for negative and indeterminate
      biopsies, respectively, vs 27% for positive biopsies; P < .0001). Multivariate
      analysis indicated that biopsy status (P < .0001) and Gleason score (P < .0001)
      were the strongest determinates of biochemical DFS. CONCLUSIONS: Two-year post-RT
      prostate biopsies were strongly predictive of subsequent DFS. Biopsies with
      severe treatment effect were considered negative.

PMID- 19117040
TI  - Benign breast lesions at risk of developing cancer--a challenging problem in
      breast cancer screening programs: five years' experience of the Breast Cancer
      Screening Program in Verona (1999-2004).
AB  - BACKGROUND: Cytology and core-needle biopsies are not always sufficient to
      exclude malignancy in benign breast lesions (BBL) that are at risk of developing
      cancer, and open biopsy often is mandatory. In screening programs, open biopsies
      performed for lesions that are at risk of developing malignancy are considered
      benign. The authors of this report evaluated the impact of the screen-detected
      BBL at risk of developing cancer that were counted in the quota of benign breast
      open biopsies in the Breast Cancer Screening Program of Verona. METHODS: Benign
      open biopsies were subdivided into 4 groups according to their risk of developing
      cancer: Histo1, normal histology; Histo2, 'pure' BBL (fibroadenoma, fibrocystic
      disease, mastitis, adenosis); Histo3, BBL with a low risk of developing cancer
      (radial scar, papilloma, papillomatosis, phyllodes tumor, mucocele-like lesion);
      and Histo4, BBL with a high risk of developing cancer (atypical columnar cell
      hyperplasia, atypical ductal hyperplasia, atypical lobular hyperplasia). RESULTS:
      Of 510 open biopsies, 83 biopsies were benign, and the ratio of benign to
      malignant biopsies was 1:5. Histo1 was observed in 4.8% of all benign open
      biopsies, Histo2 was observed in 37.4%, Histo3 was observed in 31.3%, and Histo4
      was observed 26.5%. CONCLUSIONS: BBL at risk of developing cancer may be numerous
      in screening programs. It is inappropriate to include BBL at risk of developing
      cancer in the overall benign open biopsy rate. The authors propose separating
      pure BBL from lesions at higher risk of developing cancer. To date, there is no
      evidence to support the premise that detecting high-risk proliferative lesions
      leads to benefits in terms of reduced mortality; however, these lesions need to
      be counted separately for future evaluations.

PMID- 19117041
TI  - Stressful life events and posttraumatic stress symptoms in children with cancer.
AB  - This study examined the contribution of stressful life events in posttraumatic
      stress symptoms (PTSS) stemming from childhood cancer among 121 patients. When
      controlling for demographic characteristics (age, gender, ethnicity, and
      socioeconomic status), cancer factors (treatment status, time since diagnosis,
      and cancer type), and intensity of parental PTSS, history of stressful life
      events in the child's life emerged as a salient correlate of PTSS across the
      different measures and reporting methods used in the study. Overall, children who
      had experienced more frequent and severe life stressors endorsed greater PTSS in
      relation to the cancer experience. Clinical work and future research on children
      with cancer should focus accordingly on the potential cumulative impact of
      stressful life events on PTSS.

PMID- 19117042
TI  - Evaluation of tumor response after locoregional therapies in hepatocellular
      carcinoma: are response evaluation criteria in solid tumors reliable?
AB  - BACKGROUND: Evaluation of response to treatment is a key aspect in cancer
      therapy. Response Evaluation Criteria in Solid Tumors (RECIST) are used in most
      oncology trials, but those criteria evaluate only unidimensional tumor
      measurements and disregard the extent of necrosis, which is the target of all
      effective locoregional therapies. Therefore, the European Association for the
      Study of the Liver (EASL) guidelines recommended that assessment of tumor
      response should incorporate the reduction in viable tumor burden. The current
      report provides an assessment of the agreement/concordance between both RECIST
      and the EASL guidelines for the evaluation of response to therapy. METHODS: The
      authors evaluated a cohort of 55 patients within prospective studies, including
      24 patients with hepatocellular carcinoma who underwent transarterial
      chemoembolization (TACE) with drug eluting beads (DEB-TACE) and 31 patients who
      underwent percutaneous ablation (percutaneous ethanol injection
      [PEI]/radiofrequency [RF]). Triphasic helical computed tomography scans were
      performed at baseline, at 1 month, and at 3 months after procedure, and 2
      independent radiologists evaluated tumor response. RESULTS: Evaluating response
      according to RECIST criteria, no patients achieved a complete response (CR),
      21.8% of patients achieved a partial response (PR) (none in the PEI/RF group),
      47.3% of patients had stable disease (SD), and 30.9% of patients had progressive
      disease (PD). When response was evaluated according to the EASL guidelines, 54.5%
      of patients achieved a CR, 27.3% of patients achieved a PR, 3.6% of patients had
      SD, and 14.5% had PD. The kappa coefficient was 0.193 (95% confidence interval,
      0.0893-0.2967; P < .0001). CONCLUSIONS: RECIST missed all CRs and underestimated
      the extent of partial tumor response because of tissue necrosis, wrongly
      assessing the therapeutic efficacy of locoregional therapies. This evaluation
      should incorporate the reduction in viable tumor burden as recognized by
      nonenhanced areas on dynamic imaging studies.

PMID- 19117043
TI  - Bright, color-tunable fluorescent dyes in the Vis/NIR region: establishment of
      new "tailor-made" multicolor fluorophores based on borondipyrromethene.
AB  - A new series of high-performance fluorophores named Keio Fluors (KFL), which are
      based on borondipyrromethene (BODIPY), are reported. The KFL dyes cover a wide
      spectral range from the yellow (547 nm) to the near-infrared (NIR, 738 nm)
      region, and their emission wavelength could be easily and subtly controlled based
      on simple molecular modifications only, without losing their optical properties.
      This "tailor-made" synthetic strategy for tuning the emission wavelength enabled
      the creation of fourteen KFL dyes with well-controlled emission colors (yellow,
      orange, red, far-red, and NIR). Moreover, these KFL dyes also retain their
      excellent optical properties, such as spectral bands sharper than quantum dots,
      high extinction coefficients (140,000-316,000 M(-1) cm(-1)), and high quantum
      yields (0.56-0.98), without any critical solvent polarity dependent decrease of
      their brightness. These advantageous characteristics make the KFL dyes
      potentially useful as new candidates of fluorescent standard dyes to substitute
      or to complement existing long-wavelength fluorescent dyes, such as cyanines,
      oxazines, rhodamines, or other BODIPY dyes.

PMID- 19117044
TI  - Development of fully functional proteins with novel glycosylation via enzymatic
      glycan trimming.
AB  - Recombinant glycoproteins present unique challenges to biopharmaceutical
      development, especially when efficacy is affected by glycosylation. In these
      cases, optimizing the protein's glycosylation is necessary, but difficult, since
      the glycan structures cannot be genetically encoded, and glycosylation in
      nonhuman cell lines can be very different from human glycosylation profiles. We
      are exploring a potential solution to this problem by designing enzymatic glycan
      optimization methods to produce proteins with useful glycan compositions. To
      demonstrate viability of this new approach to generating glycoprotein-based
      pharmaceuticals, the N-linked glycans of a model glycoprotein, ribonuclease B
      (RNase B), were modified using an alpha-mannosidase to produce a new glycoprotein
      with different glycan structures. The secondary structure of the native and
      modified glycoproteins was retained, as monitored using circular dichroism. An
      assay was also developed using an RNA substrate to verify that RNase B had indeed
      retained its function after being subjected to the necessary glycan modification
      conditions. This is the first study that verifies both activity and secondary
      structure of a glycoprotein after enzymatic glycan trimming for use in
      biopharmaceutical development methods. The evidence of preserved structure and
      function for a modified glycoprotein indicates that extracellular enzymatic
      modification methods could be implemented in producing designer glycoproteins.

PMID- 19117045
TI  - Influence of plasma protein binding on pharmacodynamics: Estimation of in vivo
      receptor affinities of beta blockers using a new mechanism-based PK-PD modelling
      approach.
AB  - The objective of this investigation was to examine in a systematic manner the
      influence of plasma protein binding on in vivo pharmacodynamics. Comparative
      pharmacokinetic-pharmacodynamic studies with four beta blockers were performed in
      conscious rats, using heart rate under isoprenaline-induced tachycardia as a
      pharmacodynamic endpoint. A recently proposed mechanism-based agonist-antagonist
      interaction model was used to obtain in vivo estimates of receptor affinities
      (K(B,vivo)). These values were compared with in vitro affinities (K(B,vitro)) on
      the basis of both total and free drug concentrations. For the total drug
      concentrations, the K(B,vivo) estimates were 26, 13, 6.5 and 0.89 nM for S(-)
      atenolol, S(-)-propranolol, S(-)-metoprolol and timolol. The K(B,vivo) estimates
      on the basis of the free concentrations were 25, 2.0, 5.2 and 0.56 nM,
      respectively. The K(B,vivo)-K(B,vitro) correlation for total drug concentrations
      clearly deviated from the line of identity, especially for the most highly bound
      drug S(-)-propranolol (ratio K(B,vivo)/K(B,vitro) approximately 6.8). For the
      free drug, the correlation approximated the line of identity. Using this model,
      for beta-blockers the free plasma concentration appears to be the best predictor
      of in vivo pharmacodynamics.

PMID- 19117046
TI  - Enhanced permeation of methotrexate in vitro by ion pair formation with L
      arginine.
AB  - Ion paired solutions of methotrexate in L-arginine/water/propylene glycol systems
      were evaluated for their potential to enhance the permeation of methotrexate
      across rabbit nasal mucosa in vitro. The partition coefficient of methotrexate in
      the methotrexate: L-arginine ion paired systems was observed to be 24 times
      greater than that of the methotrexate system without L-arginine. The ion pair
      formation between methotrexate and L-arginine was confirmed by a decrease in the
      conductivity of the systems in the presence of propylene glycol, a dielectric
      constant reducing agent. The permeation of methotrexate across the rabbit nasal
      mucosa from the ion paired systems was observed to be significantly greater (p <
      0.05) as compared to control systems of methotrexate solution in water and a
      sodium salt. Furthermore, a threefold increase in the flux of methotrexate was
      observed when propylene glycol was added to the ion paired systems. These results
      suggest that methotrexate: L-arginine ion paired systems have potential in
      improving the permeation of methotrexate across rabbit nasal mucosa and may form
      the basis for further development of an intranasal therapeutic system of
      methotrexate.

PMID- 19117047
TI  - Screening of heparin API by near infrared reflectance and Raman spectroscopy.
AB  - Near infrared (NIR) reflectance and laser Raman spectra for a set of 69 heparin
      powder samples obtained from several foreign and domestic suppliers were
      measured. Both the NIR and Raman spectra of individual heparin API powder samples
      were correlated with sample compositions determined from response corrected
      relative peak areas of the capillary electropherograms of the samples using a
      partial least squares (PLS) regression model. Twenty-eight sample spectra were
      used to develop PLS models for the three major sample components; heparin,
      oversulfated chondroitin sulfate (OSCS) and glycosaminoglycans (GAGs). The PLS
      models were then used to successfully predict the compositions of 41 additional
      heparin samples. The success of these rapid, nondestructive technologies to
      identify contamination of heparin with OSCS demonstrates the potential of
      spectroscopy and chemometrics for screening of processed raw materials. These
      technologies are meant for screening purposes and not meant to replace either of
      the methods (capillary electrophoresis and NMR) currently required by USP and
      FDA.

PMID- 19117048
TI  - Iontophoretically enhanced ciclopirox delivery into and across human nail plate.
AB  - Transungual delivery of antifungal drugs is hindered by the low permeability of
      human nail plates, and as such, repeated dosing over a long period of time is
      necessary for effective treatment. The objectives of this study were to explore
      the possibilities of (a) enhancing the delivery of ciclopirox (CIC) across human
      nail plates and (b) sustaining CIC delivery from the larger resultant drug depot
      in the nail plates with constant voltage iontophoresis. In vitro passive and 9 V
      cathodal iontophoretic transport experiments of CIC across human nails were
      performed. Transungual CIC delivery with Penlac was the control. The amounts of
      CIC released from and deposited in the nails were determined in drug release and
      extraction experiments, respectively. Iontophoresis increased the flux of CIC
      permeated across the nail approximately 10 times compared to passive delivery
      from the same formulation or from Penlac. A significant amount of CIC was loaded
      into and released from the nails; the CIC concentrations were estimated to be
      above the minimum inhibitory concentrations of CIC for dermatophytic molds. The
      apparent transport lag time decreased in iontophoretic transport. The results
      demonstrate that iontophoresis was able to deliver an effective amount of CIC
      into and across the nails, and this suggests the feasibility of a constant
      voltage battery-powered transungual iontophoretic device.

PMID- 19117049
TI  - Irontophoresis: transdermal delivery of iron by iontophoresis.
AB  - Transdermal delivery of iron can overcome the GI side effects and the discomfort
      associated with parenteral administration. Slow and prolonged transdermal
      delivery of iron would also avoid potential oversaturation of transferrin and
      overcome accumulation of free iron in the systemic circulation. Ferric
      pyrophosphate (FPP) has been demonstrated to be safe for systemic administration.
      Passive transdermal delivery of FPP is poor due to the impermeable skin barrier.
      Irontophoresis was developed for transdermal delivery of FPP. The predictability
      and programmability of the technique was assessed in vitro across the hairless
      rat skin. Following Irontophoresis for 6 h in hairless rats, the total serum iron
      concentration increased from 182.36 +/- 39.93 microg/dL to 317.56 +/- 28.33
      microg/dL and the transferrin saturation increased from 44.6% +/- 2.2% to 60.8%
      +/- 6.7%. Irontophoresis based iron therapy could be relatively more patient
      compliant, safe and effective treatment for iron deficiency anemia condition.

PMID- 19117050
TI  - Drug delivery trends in clinical trials and translational medicine: Updated
      analysis of ClinicalTrials.gov database.
AB  - While the number of clinical trials has continued to grow by about 20% in the
      past six months, no corresponding growth in product approval by the food and drug
      administration is seen or anticipated in the near future. Late-stage clinical
      failures due to lack of efficacy or toxicity continues to be a challenge. The
      optimization of absorption, distribution, metabolism and elimination (ADME) has
      improved drug candidate selection and reduced early clinical failure. The current
      challenge is how to avoid late stage clinical failures. Expanded knowledge of
      drug target distribution, pharmacokinetics and validated biomarkers will allow
      implementation of appropriate drug delivery and clinical trial designs to reduce
      drug exposure to off-target organs such as the liver and kidney and could reduce
      potential untoward effects. In essence, integration of drug delivery and
      targeting to reduce exposure in off-target tissues in the preclinical and
      clinical program may hold the key to increasing the odds of success in drug
      development. In this update, we briefly review data on clinical trials pertinent
      to drug delivery in the current regulatory environment. It also provides our
      analysis on the emerging trends in second generation antibody therapeutics in
      drug delivery and targeting.

PMID- 19117052
TI  - Altered gene expression in breast cancer liver metastases.
AB  - We previously developed a highly aggressive cell line from heart metastases of
      4T1 breast carcinoma (designated 4THM), which produced liver metastases
      (designated 4TLM). In this study, gene array analysis (GAEA) compared gene
      expression profiles in 4TLM with profiles in 4T1 and 4THM primary tumors. GAEA
      demonstrated that 4T1 and 4THM tumors differed in about 250 genes. Over 1,000
      genes, however, were expressed differently in 4TLM compared with primary tumors.
      A cohort of 16 genes showed significantly decreased expression in 4THM tumors,
      which decreased even further in 4TLM. Many of these genes have been implicated in
      breast cancer, and many are involved in cell adhesion and junctional complexes.
      Expression of multiple tight and adherence junction proteins was either
      downregulated or disappeared in 4TLM; downregulation of claudin 4, claudin 7 and
      gamma-catenin was confirmed by quantitative polymerase chain reaction,
      immunoblot, and immunocytochemical (ICC) analyses. At the protein level, intact
      ZO-1 was also observed in 4T1 tumors, but was not expressed in 4THM or 4TLM
      tumors. ICC demonstrated expression of gamma-catenin at the plasma membrane with
      4T1 tumors, whereas staining appeared to be nuclear/perinuclear in 4THM tumors.
      Claudin 7 staining was also seen in monocyte/pmacrophage-like cells in liver
      around metastatic lesions by ICC, and it appeared that larger 4TLM tumors
      apparently reexpressed claudin 7 RNA and protein. Our results demonstrate that
      decreased or abnormal expression of a number of cell adhesion/junctional
      proteins, including claudin 4, 7, ZO-1 and gamma-catenin, correlates with liver
      metastases, and that cell adhesion molecules in the microenvironment are also
      altered.

PMID- 19117051
TI  - Inducible site-specific recombination in neural stem/progenitor cells.
AB  - To establish a genetic tool for manipulating the neural stem/progenitor cell
      (NSC) lineage in a temporally controlled manner, we generated a transgenic mouse
      line carrying an NSC-specific nestin promoter/enhancer expressing a fusion
      protein encoding Cre recombinase coupled to modified estrogen receptor ligand
      binding domain (ER(T2)). In the background of the Cre reporter mouse strain
      Rosa26(lacZ), we show that the fusion CreER(T2) recombinase is normally silent
      but can be activated by the estrogen analog tamoxifen both in utero, in infancy,
      and in adulthood. As assayed by beta-galactosidase activity in embryonic stages,
      tamoxifen activates Cre recombinase exclusively in neurogenic cells and their
      progeny. This property persists in adult mice, but Cre activity can also be
      detected in granule neurons and Bergmann glia at the anterior of the cerebellum,
      in piriform cortex, optic nerve, and some peripheral ganglia. No obvious Cre
      activity was observed outside of the nervous system. Thus, the nestin regulated
      inducible Cre mouse line provides a powerful tool for studying the physiology and
      lineage of NSCs.

PMID- 19117053
TI  - Does the increase of endogenous steroid hormone levels also affect breast cancer
      risk in Chinese women? A case-control study in Chongqing, China.
AB  - Accumulating epidemiological evidence suggests that sex steroid hormones are
      positively associated with the development of breast cancer. However, most of
      these studies were conducted among Caucasian women and few have been carried out
      in China. To determine whether the associations of sex steroid hormone levels
      with breast cancer risk observed by and large in Caucasian populations are also
      evident in Chinese women, we conducted a case-control study in Chongqing, China.
      The study included 367 incident breast cancer patients and 367 healthy controls
      matched on menstrual status, age and periods of blood collection in the menstrual
      cycle. Plasma concentrations of estradiol, progesterone, testosterone,
      dehydroepiandrosterone sulfate (DHEAS) and sex hormone binding globulin (SHBG)
      were determined by electrochemiluminescene immunoassay (ECLIA). Conditional
      logistic regression analysis was performed to examine their associations with
      breast cancer risk. From comparisons of upper and lower tertiles, we observed
      statistically significant positive associations with breast cancer risk for
      plasma estradiol levels in follicular phase (adjusted odds ratio [OR] = 5.48, 95%
      confidence interval [CI] = 1.58-18.97), luteal phase (OR = 4.23, CI = 1.65-10.87)
      and postmenopausal (OR = 2.67, CI = 1.20-5.93); for progesterone levels in luteal
      phase (OR = 3.11, CI = 1.28-7.56), and for testosterone levels in postmenopausal
      (OR = 2.83, CI = 1.26-6.35). No significant association was found with DHEAS or
      SHBG. Our study suggests that high circulating levels of estradiol and
      testosterone are positively associated with increased breast cancer risk in
      Chinese women, which are generally consistent with the observations in Caucasian
      populations.

PMID- 19117054
TI  - Estradiol downregulation of the tumor suppressor gene BTG2 requires estrogen
      receptor-alpha and the REA corepressor.
AB  - B-cell Translocation Gene 2 (BTG2/TIS21/PC3) is an anti-proliferative tumor
      suppressor gene whose expression is significantly reduced in breast carcinomas,
      and in MCF-7 and T-47D breast cancer cell lines treated with estradiol (E2). In
      this study the mechanisms involved in E2 down regulation of BTG2 gene expression
      were examined. Depletion of ERalpha by siRNA indicated that the receptor is
      required for E2 down regulation of BTG2 mRNA levels, and cycloheximide
      experiments indicated that the effect of E2 on BTG2 expression was independent of
      intermediary protein synthesis. Chromatin immunoprecipitation analyses revealed
      that ERalpha interacts with the BTG2 promoter in a ligand-independent fashion
      whereas transfection experiments indicated that ERalpha's DNA and ligand binding
      domains are required for E2 repression of BTG promoter activity. Surprisingly,
      histone deacetylase (HDACs) activity is essential for basal expression as
      evidenced by trichostatin A inhibition of BTG2 mRNA levels. Estradiol treatment
      did not alter histone H3 acetylation although it did induce displacement of RNA
      polymerase II from the BTG2 gene. Depletion of the ER specific corepressor REA
      (Repressor of Estrogen Receptor Activity) significantly abrogated E2-mediated
      BTG2 repression. Taken together, our results reveal a requirement of HDAC
      activity for basal BTG2 expression and the ERalpha-REA interaction for estrogen
      repression of the BTG2 gene. The ability of E2-bound ERalpha and REA to suppress
      BTG2 expression indicates a positive role for this corepressor in regulation of
      breast cancer cell proliferation.

PMID- 19117055
TI  - Trichomonosis and subsequent risk of prostate cancer in the Prostate Cancer
      Prevention Trial.
AB  - We previously observed a positive association between a history of trichomonosis,
      a sexually transmitted infection caused by the protozoan, Trichomonas vaginalis,
      and prostate cancer risk in the Health Professionals Follow-up Study. To
      determine the reproducibility of this finding, we conducted a second, prospective
      investigation of trichomonosis and prostate cancer in the Prostate Cancer
      Prevention Trial. Participants were men (>or=55 years of age) with no evidence of
      prostate cancer at enrollment (n = 18,882). Men were screened annually for
      prostate cancer, and if not diagnosed during the trial, were offered an end-of
      study prostate biopsy. Cases were a sample of men diagnosed with prostate cancer
      on any biopsy after visit 2 or on their end-of-study biopsy (n = 616). Controls
      were men not diagnosed with prostate cancer during the trial or on their end-of
      study biopsy (n = 616). Controls were frequency-matched to cases by age,
      treatment arm, and family history of prostate cancer. Serum from visit 2 was
      tested for anti-T. vaginalis IgG antibodies. No association was observed between
      T. vaginalis serostatus and prostate cancer. 21.5% of cases and 24.8% of controls
      had low seropositivity, and 15.2% and 15.0% had high seropositivity. Compared to
      seronegative men, the odds ratio of prostate cancer for men with low
      seropositivity was 0.83 [95% confidence interval (CI): 0.63-1.09), and that for
      men with high seropositivity was 0.97 (95% CI: 0.70-1.34). Given the original
      strong biologic rationale and potential for prevention, additional studies are
      warranted to help resolve discrepancies between study findings and to further
      investigate this hypothesis from a variety of different approaches.

PMID- 19117056
TI  - The Karyopherin proteins, Crm1 and Karyopherin beta1, are overexpressed in
      cervical cancer and are critical for cancer cell survival and proliferation.
AB  - The Karyopherin proteins are involved in nucleo-cytoplasmic trafficking and are
      critical for protein and RNA subcellular localization. Recent studies suggest
      they are important in nuclear envelope component assembly, mitosis and
      replication. Since these are all critical cellular functions, alterations in the
      expression of the Karyopherins may have an impact on the biology of cancer cells.
      In this study, we examined the expression of the Karyopherins, Crm1, Karyopherin
      beta1 (Kpnbeta1) and Karyopherin alpha2 (Kpnalpha2), in cervical tissue and cell
      lines. The functional significance of these proteins to cancer cells was
      investigated using individual siRNAs to inhibit their expression. Microarrays,
      quantitative RT-PCR and immunofluorescence revealed significantly higher
      expression of Crm1, Kpnbeta1 and Kpnalpha2 in cervical cancer compared to normal
      tissue. Expression levels were similarly elevated in cervical cancer cell lines
      compared to normal cells, and in transformed epithelial and fibroblast cells.
      Inhibition of Crm1 and Kpnbeta1 in cancer cells significantly reduced cell
      proliferation, while Kpnalpha2 inhibition had no effect. Noncancer cells were
      unaffected by the inhibition of Crm1 and Kpnbeta1. The reduction in proliferation
      of cancer cells was associated with an increase in a subG1 population by cell
      cycle analysis and Caspase-3/7 assays revealed increased apoptosis. Crm1 and
      Kpnbeta1 siRNA-induced apoptosis was accompanied by an increase in the levels of
      growth inhibitory proteins, p53, p27, p21 and p18. Our results demonstrate that
      Crm1, Kpnbeta1 and Kpnalpha2 are overexpressed in cervical cancer and that
      inhibiting the expression of Crm1 and Kpnbeta1, not Kpnalpha2, induces cancer
      cell death, making Crm1 and Kpnbeta1 promising candidates as both biomarkers and
      potential anticancer therapeutic targets.

PMID- 19117057
TI  - MET gene amplification or EGFR mutation activate MET in lung cancers untreated
      with EGFR tyrosine kinase inhibitors.
AB  - We analyzed MET protein and copy number in NSCLC with or without EGFR mutations
      untreated with EGFR tyrosine kinase inhibitors (TKIs). MET copy number was
      examined in 28 NSCLC and 4 human bronchial epithelial cell lines (HBEC) and 100
      primary tumors using quantitative real-time PCR. Positive results were confirmed
      by array comparative genomic hybridization and fluorescence in-situ
      hybridization. Total and phospho-MET protein expression was determined in 24
      NSCLC and 2 HBEC cell lines using Western blot. EGFR mutations were examined for
      exon 19 deletions, T790M, and L858R. Knockdown of EGFR with siRNA was performed
      to examine the relation between EGFR and MET activation. High-level MET
      amplification was observed in 3 of 28 NSCLC cell lines and in 2 of 100 primary
      lung tumors that had not been treated with EGFR-TKIs. MET protein was highly
      expressed and phosphorylated in all the 3 cell lines with high MET amplification.
      In contrast, 6 NSCLC cell lines showed phospho-MET among 21 NSCLC cell lines
      without MET amplification (p = 0.042). Furthermore, those 6 cell lines harboring
      phospho-MET expression without MET amplification were all EGFR mutant (p =
      0.0039). siRNA-mediated knockdown of EGFR abolished phospho-MET expression in
      examined 3 EGFR mutant cell lines of which MET gene copy number was not
      amplified. By contrast, phospho-MET expression in 2 cell lines with amplified MET
      gene was not down-regulated by knockdown of EGFR. Our results indicated that MET
      amplification was present in untreated NSCLC and EGFR mutation or MET
      amplification activated MET protein in NSCLC.

PMID- 19117059
TI  - Downregulation of ZIP kinase is associated with tumor invasion, metastasis and
      poor prognosis in gastric cancer.
AB  - Deletion of 19p13 is one of the most frequent genetic changes in gastric
      carcinoma (GC), implying the existence of a tumor suppressor gene (TSG) that
      plays an important role in GC development. To identify the candidate TSG at 19p,
      array-comparative genomic hybridization (CGH) was applied to study DNA copy
      number changes on chromosomes 3, 5p, 13, 16q and 19. The result showed that gains
      of 16q21, 19q13.1, 5p15.1 and 3q26.31, and losses of 3p21.32, 3p22.2, 19q13.33
      and 19p13.3, were frequently detected by array-CGH. One candidate TSG, ZIP kinase
      (ZIPK), at 19p13.3 was further characterized by immunohistochemistry using a
      tissue microarray containing 172 primary GCs. Downregulation of ZIPK was detected
      in 111/162 informative GCs, which was significantly associated with invasion,
      metastasis and poorer prognosis of GC. To investigate the association of the
      downregulation of ZIPK with apoptosis, apoptosis assay (TUNEL) was used to
      compare the apoptotic index between GCs with normal expression and downregulation
      of ZIPK. TUNEL assay showed that the apoptotic index in GCs with normal ZIPK
      expression was significantly higher than that in GCs with downregulation of ZIPK
      (p < 0.001), indicating that ZIPK plays an important pro-apoptotic role in GC.
      Taken together, we demonstrated here that ZIPK is a tumor suppresser gene and
      plays an important role in GC development through its pro-apoptotic function.
      Downregulation of ZIPK can be used to evaluate tumor invasiveness, metastasis and
      to predict survival of GC.

PMID- 19117058
TI  - Flavonoid intake and ovarian cancer risk in a population-based case-control
      study.
AB  - Several recent studies have evaluated the association between dietary flavonoid
      intake and ovarian cancer risk, and all reported significant or suggestive
      inverse associations with certain flavonoids or flavonoid subclasses; however,
      most of these studies were small to moderate in size. We, therefore, examined
      this association in a large, population-based case-control study. We calculated
      intake of 5 common dietary flavonoids (myricetin, kaempferol, quercetin,
      luteolin, and apigenin), as well as total intake of these flavonoids, for 1,141
      cases and 1,183 frequency-matched controls. We used unconditional logistic
      regression to estimate the relative risk (RR) of ovarian cancer for each quintile
      of flavonoid intake when compared with the lowest quintile. We did not observe an
      association between total flavonoid intake and ovarian cancer risk. The
      multivariable-adjusted RR for the highest versus lowest quintile of total
      flavonoid intake was 1.06 (95% confidence interval [CI] = 0.78-1.45). In analyses
      of each individual flavonoid, only intake of apigenin was associated with a
      borderline significant decrease in risk (RR, highest vs. lowest quintile = 0.79,
      95% CI = 0.59-1.06; p-trend = 0.26), and this association was significant after
      adjustment for intake of the other 4 individual flavonoids (comparable RR = 0.72,
      95% CI = 0.53-0.98; p-trend = 0.09). These results provide limited support for an
      association between flavonoid intake and ovarian cancer risk. However, given the
      findings of previous studies and the biologic plausibility of this association,
      additional studies are warranted.

PMID- 19117060
TI  - Tumour growth fraction measured by immunohistochemical staining of Ki67 is an
      independent prognostic factor in preoperative prostate biopsies with small-volume
      or low-grade prostate cancer.
AB  - Accurate prognostic parameters in prostate biopsies are needed to better counsel
      individual patients with prostate cancer. We evaluated the prognostic impact of
      morphologic and immunohistochemical parameters in preoperative prostate cancer
      biopsies. A consecutive series of prostate biopsies of 279 men (72% with clinical
      stage T1c and 23% with T2) who subsequently underwent radical prostatectomy was
      prospectively analysed for Gleason score, number and percentage of positive cores
      (NPC, PPC), total percentage of biopsy tissue with tumour (TPT), maximum tumour
      percentage per core (MTP), and expression of Ki67, Bcl-2 and p53. All biopsy
      features were significantly associated with at least one feature of the radical
      prostatectomy specimen. pT stage was independently predicted by PSA, seminal
      vesicle invasion by Ki67 LI, positive margins by PSA and MTP, large tumour
      diameter by PSA and PPC, and Gleason score by biopsy Gleason score, MTP, and Ki67
      LI, respectively. Biopsy Gleason score, NPC (1 vs. >1), TPT (<7 vs. >or=7%), and
      Ki67 LI (<10 vs. >or=10%) were significant predictors of biochemical recurrence
      after radical prostatectomy (p < 0.01, each). KI67 LI was the only independent
      prognostic factor in case of a low TPT (<7%) or low Gleason score (<7), the
      hazard ratio being 6.76 and 6.44, respectively. In summary, preoperative Gleason
      score, NPC, TPT and Ki67 LI significantly predict the risk of recurrence after
      radical prostatectomy, and Ki67 is an independent prognosticator in biopsies with
      low-volume or low-grade prostate cancer. Analysis of Ki67 LI in these biopsies
      may help to better identify patients with clinically insignificant prostate
      cancer.

PMID- 19117061
TI  - Sex-specific familial risks of urinary bladder cancer and associated neoplasms in
      Sweden.
AB  - Male gender and a family history of cancer are established risk factors for
      urinary bladder neoplasms. This study used the latest update of the Swedish
      Family-Cancer Database, which includes 42,255 bladder cancer patients, to
      investigate the sex-specific incidences and types of tumors in relatives of
      bladder cancer patients. Men with parents or siblings affected by lung cancer did
      not show an increased risk of bladder neoplasms. Among women, the familial
      association was restricted to daughters of women with lung cancer. Brothers
      showed higher risks than the sons of bladder cancer patients. Men older than 54
      years were at an increased risk of bladder cancer only if their fathers or
      siblings were diagnosed after age 65 years. The present data indicated a limited
      contribution of smoking to the familial clustering of bladder cancer with other
      neoplasms. The dependence of the relative risks on the type of familial
      relationship probably reflected a heterogeneous character of familial
      aggregation. Age-specific results suggested differential risk factors for tumors
      diagnosed before 50 years of age versus neoplasms detected later in life. The
      present data may guide the design of forthcoming gene identification studies and
      the interpretation of the genome-wide association studies that are about to be
      published.

PMID- 19117062
TI  - Gestational morphogenesis of the uterine epithelium of the gummy shark (Mustelus
      antarcticus).
AB  - Developing embryos of the non-placental, viviparous gummy shark (Mustelus
      antarcticus) are supplied with yolk from external and internal yolk sacs
      throughout the initial stages of gestation. Yolk supplies are exhausted by the
      7th month of an 11-12 month gestation. During embryonic development, there is an
      approximate 800% gain in dry mass. These factors suggest nutrients are
      transferred from the mother to the young. The results of the present study
      provide some insights into how this is occurring. The uteri are paired and both
      are functional. Using both light and transmission electron microscopy, regions of
      the uterus were examined throughout maturation and gestation. The layers of the
      uterine wall throughout the entire length are similar to the uteri of other
      chondrichthyans previously examined. The uterine epithelium of the body of the
      uterus is smooth contoured, does not form villi, and undergoes cyclical and
      secretory changes throughout maturity and gestation. In immature uteri, the
      epithelium is simple columnar with minimal periodic acid-Schiff-positive and
      Alcian blue-positive secretory vesicles. In mature uteri, the epithelium is
      highly stratified with cuboidal cells containing numerous Alcian blue-positive
      and periodic acid-Schiff-positive vesicles. With pregnancy, prominent changes
      include a reduction in the number of cell layers, a reduction in cell size, a
      reduction in the connective tissue intervening between epithelium and blood
      vessel endothelium, and an increase in blood vessel number and size, so that at
      term, the uterine compartment consists of a single layer of squamous cells
      immediately underlain by sinusoidal-like blood vessels. These features along with
      a small number of secretory vesicles, dilated intercellular spaces, and clear
      transport vesicles suggest the transepithelial transfer of water and minerals
      from the maternal to embryonic environment, supplemented by minimal uterine
      secretions. This is defined as minimal histotrophy and this article represents
      the first detailed description of this reproductive mode.

PMID- 19117063
TI  - Geographic variation in otolith morphology among freshwater populations of
      Aphanius dispar (Teleostei, Cyprinodontiformes) from the southeastern Arabian
      Peninsula.
AB  - Aphanius Nardo is a large genus of teleost fishes in the Old World, with 19
      described species. Several of these species have only recently been recognized
      and additional species can be expected from isolated populations in remote areas.
      We show here that otolith morphology and statistical analyses of otolith
      variables can contribute to the detection of genetic differentiation in Aphanius.
      We studied samples of eight Aphanius dispar populations from the southeastern
      part of the Arabian Peninsula. Two populations originate from freshwater habitats
      far inland and probably have been isolated since the late Holocene some 4,000
      years ago, three populations come from freshwater habitats with occasional
      connections to the sea, one population originates from a coastal site, and two
      were artificially introduced populations. The coastal population is interpreted
      as possessing the basic otolith type of A. dispar. The basic otolith type also
      occurs in fishes from the freshwater habitat which is located closest to the
      coast. Otoliths from the two other freshwater populations with occasional
      connections to the coast differ slightly from the basic type. However, the two
      populations from the long-term isolated freshwater habitats far inland show
      distinct morphological changes. Our results are consistent with the hypotheses
      that i) otolith morphology is primarily genetically determined and is little
      influenced by physical parameters of the habitat, and ii) isolated A. dispar
      populations may be capable of evolving into new species within short periods of
      time.

PMID- 19117064
TI  - Chondrogenesis and homology of the visceral skeleton in the little skate,
      Leucoraja erinacea (Chondrichthyes: Batoidea).
AB  - Chondrichthyan fishes possess visceral skeletons that differ considerably,
      morphologically, from those of their sister taxon, the osteichthyans. Here, we
      use histological techniques and whole-mount skeletal preparations to visualize
      and describe the sequence of visceral skeletal condensation and chondrogenesis in
      a chondrichthyan, the little skate (Leucoraja erinacea). We demonstrate that
      visceral skeletal condensation begins rostrally, with the mandibular arch, and
      progresses caudally with the hyoid arch and posterior branchial arches condensing
      soon after. We provide a detailed account of the condensation and chondrogenesis
      of all major components of the L. erinacea visceral skeleton and discuss these
      data in the context of what is known from classical descriptions of
      chondrichthyan visceral skeletal development. Significant differences exist
      between the hypobranchial and basibranchial skeleton of L. erinacea and other
      chondrichthyan species, and the possible evolutionary and developmental
      significance of this is considered. We discuss the homology of the chondrichthyan
      hyoid arch and, based on patterns of mesenchymal condensation, we propose a model
      of condensation splitting and diversification that may account for the
      morphological diversification of gnathostome branchial arch derivatives. Finally,
      we suggest that the unique presence of certain visceral skeletal elements in
      chondrichthyans make oviparous chondrichthyans an ideal system for addressing
      questions of endoskeletal axial patterning during development.

PMID- 19117065
TI  - Tension patterns of the anteromedial and posterolateral grafts in a double-bundle
      anterior cruciate ligament reconstruction.
AB  - The two functional bundles of the anterior cruciate ligament (ACL), namely, the
      anteromedial (AM) and posterolateral (PL) bundles, must work in concert to
      control displacement of the tibia relative to the femur for complex motions.
      Thus, the replacement graft(s) for a torn ACL should possess similar tension
      patterns. The objective of the study was to examine whether a double-bundle ACL
      reconstruction with the semitendinosus-gracilis autografts could replicate the
      tension patterns of those for the intact ACL under controlled in vitro loading
      conditions. By means of a robotic/universal force moment sensor (UFS) testing
      system, the in situ force vectors (both magnitude and direction) for the AM and
      PL bundles of the ACL, as well as their respective replacement grafts, were
      determined and compared on nine human cadaveric knees. It was found that double
      bundle ACL reconstruction could closely replicate the in situ force vectors.
      Under a 134-N anterior tibial load, the resultant force vectors for the intact
      ACL and the reconstructed ACL had a difference of 5 to 11 N (p > 0.05) in
      magnitude and 1 to 13 degrees (p > 0.05) in direction. Whereas, under combined
      rotatory loads of 10-N-m valgus and 5-N-m internal tibial torques, the
      corresponding differences were 10 to 16 N and 4 degrees to 11 degrees,
      respectively. Again, there were no statistically significant differences except
      at 30 degrees of flexion where the force vector for the AM graft had a 15 degrees
      (p < 0.05) lower elevation angle than did the AM bundle.

PMID- 19117066
TI  - Low-magnitude high-frequency mechanical signals accelerate and augment
      endochondral bone repair: preliminary evidence of efficacy.
AB  - Fracture healing can be enhanced by load bearing, but the specific components of
      the mechanical environment which can augment or accelerate the process remain
      unknown. The ability of low-magnitude, high-frequency mechanical signals,
      anabolic in bone tissue, are evaluated here for their ability to influence
      fracture healing. The potential for short duration (17 min), extremely low
      magnitude (25 microm), high-frequency (30 Hz) interfragmentary displacements to
      enhance fracture healing was evaluated in a mid-diaphyseal, 3-mm osteotomy of the
      sheep tibia. In a pilot study of proof of concept and clinical relevance, healing
      in osteotomies stabilized with rigid external fixation (Control: n = 4), were
      compared to the healing status of osteotomies with the same stiffness of
      fixation, but supplemented with daily mechanical loading ( EXPERIMENTAL: n = 4).
      These 25-microm displacements, induced by a ferroactive shape-memory alloy
      ("smart" material) incorporated into the body of the external fixator, were less
      than 1% of the 3-mm fracture gap, and less than 6% of the 0.45-mm displacement
      measured at the site during ambulation (p < 0.001). At 10-weeks post-op, the
      callus in the EXPERIMENTAL group was 3.6-fold stiffer (p < 0.03), 2.5-fold
      stronger (p = 0.05), and 29% larger (p < 0.01) than Controls. Bone mineral
      content was 52% greater in the EXPERIMENTAL group (p < 0.02), with a 2.6-fold
      increase in bone mineral content (BMC) in the region of the periosteum (p <
      0.001). These data reinforce the critical role of mechanical factors in the
      enhancement of fracture healing, and emphasize that the signals need not be large
      to be influential and potentially clinically advantageous to the restoration of
      function.

PMID- 19117067
TI  - Kinematical and functional improvements of trigger digits after sonographically
      assisted percutaneous release of the A1 pulley.
AB  - We present evidence of kinematic and functional improvements of the trigger digit
      after sonographically assisted percutaneous release using quantitative motion
      analyses and functional assessments, respectively. Twenty-two patients with
      idiopathic trigger digits, who received the surgery, were recruited. A motion
      tracking system was used to measure the assigned kinematics parameters at the
      presurgical visit and at 1, 4, and 12 weeks after surgery. The hand strength and
      functional outcome were also obtained using dynamometer and self-report
      questionnaire assessments. The hand strength, maximal workspace, and joint range
      of motion of the involved digit were significantly smaller than that of the
      intact finger on the contralateral hand before surgery. The triggering phenomenon
      of the involved digit was significantly higher than that of the corresponding
      finger in the intact hand using a subscribed angular acceleration factor. The
      repeated measures showed that the workspace, joint range of motion, hand
      strength, and triggering effect of the involved hand significantly improved in
      follow-up examinations after the surgical intervention. Painful movement or
      insufficient tendon excursion of the trigger digit can cause loss of movement and
      strength, thus interfering with functional performance. After the disappearance
      of the pain and triggering by sonographically assisted percutaneous release,
      improvements in kinematics and function were objectively quantified in this
      study.

PMID- 19117068
TI  - Relevance of bone graft viability in a goat transverse process model.
AB  - Little is known about the mechanism by which autologous bone grafts are so
      successful. The relevance of viable osteogenic cells, which is a prominent
      difference between autologous bone graft and conventional alternatives, is
      especially controversial. With the emergence of bone tissue engineering,
      knowledge of the exact role of these cells has become crucial. The most obvious
      question to answer is whether viability of the graft has an effect on bone
      formation. In the current study, we investigated this effect of bone graft
      viability in a transverse process model that represents the initial bone
      formation in posterolateral spinal fusion. Eight goats received viable and
      devitalized autologous bone grafts in chambers mounted on the decorticated lumbar
      transverse processes. In addition, five goats received empty chambers. Histology
      and histomorphometry were performed after a 12-week implantation, and the
      dynamics of bone formation was monitored by sequential fluorochrome labeling. An
      obvious qualitative effect of viability was demonstrated by the presence of early
      onset osteogenesis distant from the transverse process bone in the viable grafts
      only. Quantitative analysis indicated about 30% more bone in the viable grafts,
      however, this difference was not statistically significant. In the empty
      chambers, bone was found in comparable quantities. We conclude that there is a
      qualitative advantage of graft viability in terms of early graft-derived
      osteogenesis. However, this advantage did not lead to significantly more bone
      formation in the viable bone grafts.

PMID- 19117072
TI  - Comparison of idiopathic thrombocytopenic purpura in children between 3 months
      and 2 years versus 2-5 years.
AB  - It has been reported that infantile idiopathic thrombocytopenic purpura (ITP) has
      different clinical features than ITP seen in older ages and classification of
      bleeding sites and grading of bleeding severity can be used in determining the
      risk of bleeding. In this study, patients with ITP were divided into two groups
      according to age (<2 years and 2-5 years). The clinical features, laboratory
      findings, treatment modalities, rate of response and chronicity, bleeding sites,
      grades of bleeding were compared between each group. No significant differences
      were established.

PMID- 19117073
TI  - By the way, doctor.  What UVA-blocking ingredients should I look for in a
      sunscreen?  And does a higher SPF rating mean greater UVA protection?

PMID- 19117074
TI  - Abstracts of the HOPA/ISOPP 2008 Joint Annual Conference. June 18-21, 2008.

PMID- 19117075
TI  - [An introduction to kampo medicine].

PMID- 19117076
TI  - Can sugars be produced from fatty acids? A test case for pathway analysis tools.
AB  - MOTIVATION: In recent years, several methods have been proposed for determining
      metabolic pathways in an automated way based on network topology. The aim of this
      work is to analyse these methods by tackling a concrete example relevant in
      biochemistry. It concerns the question whether even-chain fatty acids, being the
      most important constituents of lipids, can be converted into sugars at steady
      state. It was proved five decades ago that this conversion using the Krebs cycle
      is impossible unless the enzymes of the glyoxylate shunt (or alternative
      bypasses) are present in the system. Using this example, we can compare the
      various methods in pathway analysis. RESULTS: Elementary modes analysis (EMA) of
      a set of enzymes corresponding to the Krebs cycle, glycolysis and gluconeogenesis
      supports the scientific evidence showing that there is no pathway capable of
      converting acetyl-CoA to glucose at steady state. This conversion is possible
      after the addition of isocitrate lyase and malate synthase (forming the
      glyoxylate shunt) to the system. Dealing with the same example, we compare EMA
      with two tools based on graph theory available online, PathFinding and Pathway
      Hunter Tool. These automated network generating tools do not succeed in
      predicting the conversions known from experiment. They sometimes generate
      unbalanced paths and reveal problems identifying side metabolites that are not
      responsible for the carbon net flux. This shows that, for metabolic pathway
      analysis, it is important to consider the topology (including bimolecular
      reactions) and stoichiometry of metabolic systems, as is done in EMA.

PMID- 19117077
TI  - Proceedings from the 2006 annual meeting of the ISAM (International Society of
      Addiction Medicine), Oporto, Portugal.

PMID- 19117078
TI  - Readers respond to "Responding to the American siege against continuing medical
      education".

PMID- 19117079
TI  - [Complex neurotropic drugs and the problem of optimizing of pharmacotherapy in
      neurology].

PMID- 19117081
TI  - Readers' and author's responses to "Physicians for sale: how medical professional
      organizations exploit their members".

PMID- 19117080
TI  - Conformational Closure of the Catalytic Site of Human CD38 Induced by Calcium.
AB  - First identified on the surface of lymphoids as a type II transmembrane protein,
      CD38 has now been established to have dual functions not only as a receptor but
      also as a multifunctional enzyme,catalyzing the synthesis of and hydrolysis of a
      general calcium messenger molecule, cyclic ADP-ribose(cADPR). The receptorial
      functions of CD38 include the induction of cell adhesion,
      differentiation,apoptosis, and cytokine production upon antibody ligation. Here
      we determined the crystal structure of calcium-loaded human CD38 at 1.45 A
      resolution which reveals that CD38 undergoes dramatic structural changes to an
      inhibited conformation in the presence of calcium. The structural changes are
      highly localized and occur in only two regions. The first region is part of the
      active site and consists of residues 121-141.In the presence of calcium, W125
      moves 5 A into the active site and forms hydrophobic interactions with W189. The
      movement closes the active site pocket and reduces entry of substrates, resulting
      in inhibition of the enzymatic activity. The structural role of calcium in
      inducing these conformational changes is readily visualized in the crystal
      structure. The other region that undergoes calcium-induced changes is at the
      receptor region, where a highly ordered helix is unraveled to a random coil. The
      results suggest a novel conformational coupling mechanism, whereby protein
      interaction targeted at the receptor region can effectively regulate the
      enzymatic activity of CD38.

PMID- 19117082
TI  - Readers' and author's responses to "Physicians for sale: how medical professional
      organizations exploit their members".

PMID- 19117083
TI  - Readers' and author's responses to "Electronic personal health records: should
      doctors worry?".

PMID- 19117084
TI  - Safety of barley starch syrup in patients with allergy to cereals.
AB  - It is not known whether trace amounts of proteins that may remain in cereal
      starch-derived food ingredients even after food processing can trigger allergic
      symptoms in cereal-allergic individuals. The aim of this study was to find out if
      barley starch syrup causes allergic reactions in patients with allergy to wheat,
      barley, rye or oats. Fifteen children with allergy to these cereals, confirmed by
      double-blind placebo-controlled food challenge (DBPCFC), were selected for the
      study. When exposed to cereals, seven of the children (47%) showed immediate type
      reactions, such as urticaria, rash or anaphylaxis. Eight of the children (53%)
      showed delayed type reactions, such as deterioration of atopic dermatitis or
      diarrhoea. The fifteen children with allergy to cereals were exposed to barley
      starch syrup in DBPCFC and none of them showed any objective signs of allergy. On
      skin-prick tests (SPT), five of the children (33.3%) showed a positive (>or= 3
      mm) reaction to at least one of the cereals but none of them to barley starch
      syrup. This study confirmed with 98% confidence that at least 90% of the patients
      with verified allergy to cereals will not react with allergic symptoms to barley
      starch syrup.

PMID- 19117085
TI  - Changes in tumor vascularity depicted by contrast-enhanced ultrasonography as a
      predictor of chemotherapeutic effect in patients with unresectable pancreatic
      cancer.
AB  - OBJECTIVES: This study was conducted to assess changes in tumor vascularity using
      contrast-enhanced ultrasonography in patients with pancreatic carcinoma under
      systemic chemotherapy and to examine the correlation among vascular change,
      clinicopathologic factors, and outcome. METHODS: Forty-one consecutive patients
      with histopathologically confirmed pancreatic carcinoma who had distant
      metastases and were under systemic chemotherapy were recruited. Contrast-enhanced
      ultrasonography was performed before and after 1 and 2 cycles of treatment.The
      vascular signals from the tumor were continuously recorded,and the highest signal
      intensity was selected and classified into 5 categories by their intensity.
      RESULTS: As for the tumor response determined by dynamic computed tomography
      after 2 cycles, 6 patients showed a partial response, 25 remained stable, and in
      10 patients, the disease progressed. A significant relationship was observed
      between vascular change after 1 cycle and tumor response (P G 0.001). Progression
      free survival and overall survival were significantly short in the case of
      patients showing increased vascularity after 1 and 2 cycles of chemotherapy,
      compared with those who did not (P G 0.001). CONCLUSIONS: Contrast-enhanced
      ultrasonography was useful to evaluate tumor vascular changes and thereby the
      effect of systemic chemotherapy, as well as the prognosis of patients with
      advanced pancreatic carcinoma.

PMID- 19117086
TI  - Antiproliferative effects of CC-8062 and CC-8075 in pancreatic cancer cells.
AB  - OBJECTIVES: Pancreatic cancer is one of the leading causes of cancer related
      deaths in the western world. It is also resistant to most chemotherapeutic
      modalities. Phosphodiesterase-4 inhibitors (PDE4is) have found applications in
      the treatment of respiratory diseases. The aim of this study is to investigate
      the cytotoxic effect of 2 novel PDE4is, the CC-8075 and CC-8062 compounds in
      pancreatic cancer cells. METHODS: Cell proliferation was measured using the
      sulforhodamine B protein dye. Induction of apoptosis was detected using enzyme
      linked immunosorbent assay. Regulation of proteins and posttranslational
      modifications were determined using immunoblotting. RESULTS: Treatment of
      pancreatic cancer cells with CC-8075 and CC-8062 reduces their proliferation and
      increases apoptosis that is caspase dependent in T3M4 cells. Furthermore, PDE4is
      increase phosphorylation of p38MAPK, mitogen-activated protein kinase (MAPK)
      kinase 3/6,MAPKYactivated protein kinase 2, Atf2, and Hsp27. The use of
      thep38MAPK-specific inhibitors SB202190 and SB203580 results in a modest
      reduction in PDE4i-induced apoptosis in T3M4 cells. Also, retinoids enhance
      apoptosis induced by CC-8075 and CC-8062 in GER cells. CONCLUSIONS: These results
      highlight the antiproliferative effects of the phosphodiesterase inhibitors CC
      8075 and CC-8062 in pancreatic cancer cells and suggest that activation of
      p38MAPK signaling pathway may be associated with this process.

PMID- 19117087
TI  - Gene expression profiling of adenosine triphosphate-binding cassette transporters
      in response to K-ras activation and hypoxia in human pancreatic cancer cell
      cultures.
AB  - OBJECTIVES: Pancreatic cancer (PC) is hypoxic and highly resistant to
      conventional chemotherapy. We sought to determine whether K-ras oncogene and/or
      hypoxia can induce expression of drug resistance-promoting adenosine triphosphate
      binding cassette (ABC) transporters in human PC cell lines. METHODS: Immortalized
      near-normal human pancreatic ductal epithelial(HPDE) cells, HPDE cells expressing
      K-rasG12V oncogene, and PCcell lines (MIA PaCa-2, PANC-1, BxPC-3) were subjected
      to hypoxia and examined for messenger RNA expression of 48 ABC transporters.
      RESULTS: Mutant K-ras activation and/or hypoxia of HPDE cells led to induction of
      various ABC transporters. In the case of PC cell lines, no clear correlation was
      found between expression of constitutively active K-ras and global ABC
      transporter expression. Moreover, hypoxic treatment of PC cell lines had
      different effects on ABC transporter expression.Importantly, PC cell lines did
      not express the multidrug resistance 1 ABC transporter, a major mechanism of drug
      resistance. However, multi drug resistance 1 expression in the cells was up
      regulated in response to continuous exposure to low doses of vincristine,
      indicating that drug resistance could be induced. CONCLUSIONS: Expression of K
      ras oncogene and hypoxia, as well as exposure to drugs, can contribute to drug
      resistance in PC cells.

PMID- 19117088
TI  - Response to Linberg et al. Natalizumab alters transcriptional expression profiles
      of blood cell subpopulations of multiple sclerosis patients.

PMID- 19117089
TI  - Airway skills.

PMID- 19117090
TI  - The bunged bung--one-way valve malfunction during elective surgery--reply.

PMID- 19117091
TI  - 'Universal' leak test?

PMID- 19117092
TI  - Using an intravascular device to reverse refractory burn-associated hypothermia.

PMID- 19117093
TI  - The 30th Medical 10 run.

PMID- 19117094
TI  - Minimum FGF2 binding structural requirements of heparin and heparan sulfate
      oligosaccharides as determined by NMR spectroscopy.
AB  - Heparin and heparan sulfate (HS) glycosaminoglycans (HSGAGs) are sulfated
      polysaccharidesthat play important roles in fundamental biological processes by
      binding to proteins. The prototypic exampleof HSGAG-protein interactions is that
      with the fibroblast growth factors (FGFs), specifically FGF1 andFGF2. Structural
      and biochemical studies have shown that the chain length, sulfation pattern,
      andconformation of HSGAGs play a critical role in FGF binding and activity.
      Previously, we showed that atetrasaccharide of the form ANS,6X-I2S-ANS,6X-I2S-OPr
      (where X is OH or O-sulfate and Pr is propyl) withat least one of the ANS,6X
      residues having a 6-O sulfate group was the minimum binding motif for
      FGF1[Guerrini, M., Agulles, T., Bisio, A., Hricovini, M., Lay, L., Naggi, A.,
      Poletti, L., Sturiale, L., Torri, G.,and Casu, B. (2002) Biochem. Biophys. Res.
      Commun. 292, 222-230]. We report NMR structural analysisusing two-dimensional NOE
      spectroscopy (2D-NOESY) and transferred NOESY (trNOESY) on a non-6-O-sulfated
      synthetic tetrasaccharide TETRA (ANS-I2S-ANS-I2S-OPr) both in its free state and
      bound toFGF2. This tetrasaccharide comprises both the structural trisaccharide
      motif ANS-I2S-ANS that forms "kinks"in longer heparin chains induced by FGF
      binding [Raman, R., Venkataraman, G., Ernst, S., Sasisekharan,V., and
      Sasisekharan, R. (2003) Proc. Natl. Acad. Sci. U.S.A. 100, 2357-2362] and the
      common bindingmotif I2S-ANS-I2S present in octasaccharides that exhibited strong
      FGF2 binding [Kreuger, J., Salmivirta,M., Sturiale, L., Gimenez-Gallego, G., and
      Lindahl, U. (2001) J. Biol. Chem. 276, 30744-30752]. Thesedata suggest that TETRA
      could be the shortest HSGAG oligosaccharide that binds to FGF2. Furthermore,our
      study confirms that both the IdoA residues in TETRA adopt the chair 1C4
      conformation upon FGF2binding to provide the best molecular fit in contrast to an
      analogous 6-O-sulfated tetrasaccharide motifobserved in the FGF2-HSGAG cocrystal
      structure where one of the IdoAs adopts skew-boat 2SOconformation. Thus, our
      study highlights the fact that the conformational plurality of IdoA is able
      toaccommodate the changes in the sulfation pattern to provide the necessary
      specificity for protein binding.

PMID- 19117096
TI  - Smoking: unknown cardiovascular risk factors.

PMID- 19117095
TI  - (15)N{(31)P} REDOR NMR studies of the binding of phosphonate reaction
      intermediate analogues to Saccharomyces cerevisiae lumazine synthase.
AB  - Lumazine synthase catalyzes the reaction of 5-amino-6-D-ribitylamino-2,4(1H,3H)
      pyrimidinedione(1) with (S)-3,4-dihydroxybutanone 4-phosphate (2) to afford 6,7
      dimethyl-8-D-ribityllumazine(3), the immediate biosynthetic precursor of
      riboflavin. The overall reaction implies a series of intermediates that are
      incompletely understood. The 15N{31P} REDOR NMR spectra of three metabolically
      stable phosphonate reaction intermediate analogues complexed to Saccharomyces
      cereVisiae lumazine synthase have been obtained at 7 and 12 T. Distances from the
      phosphorus atoms of the ligands to the side chain nitrogens of Lys92, His97,
      Arg136, and His148 have been determined. These distances were used in combination
      with the X-ray crystal coordinates of one of the intermediate analogues complexed
      with the enzyme in a series of distance-restrained molecular dynamics
      simulations. The resulting models indicate mobility of the Lys92 side chain,
      which could facilitate the exchange of inorganic phosphate eliminated from the
      substrate in one reaction, with the organic phosphate-containing substrate
      necessary for the next reaction.

PMID- 19117097
TI  - Peritoneal dialysis: a "kinder,gentler" treatment for the elderly?

PMID- 19117098
TI  - SUMO Protocols. Preface.

PMID- 19117100
TI  - [Breast and endocrine tumor].

PMID- 19117099
TI  - Feminism, pragmatism or both? Czech radical nationalism and the woman question,
      1898-1914.

PMID- 19117101
TI  - [Development of diagnosis technology for breast cancer].

PMID- 19117102
TI  - [Treatment for breast cancer and endocrine neoplasm].

PMID- 19117103
TI  - [International and Japanese views of risk factor for breast cancer].

PMID- 19117104
TI  - Finding local solutions to meet local need.

PMID- 19117105
TI  - Change takes time.

PMID- 19117106
TI  - National party bias obvious.

PMID- 19117108
TI  - Facing the global health crisis.

PMID- 19117107
TI  - A badge for overseas nurses perhaps?

PMID- 19117109
TI  - Hollow victories in a country under seige.

PMID- 19117110
TI  - A mixed pictures: the experiences of overseas-trained nurses in New Zealand.

PMID- 19117111
TI  - Making the case for case study research.

PMID- 19117112
TI  - Journal club offers new opportunities.

PMID- 19117113
TI  - Dedicated education units--a new way of supporting clinical learning.

PMID- 19117114
TI  - The roads less travelled.

PMID- 19117115
TI  - Debating international workforce issues.

PMID- 19117116
TI  - Chronic kidney disease stages 3-5 and cardiovascular disease in the veterans
      affairs population.
AB  - AIM: Cardiovascular complications are common in patients with chronic kidney
      disease in the general population. The study aims to investigate the prevalence
      and prognosis of CKD stages 3-5 in the veterans affairs (VA) population, which is
      sicker with more co-morbid conditions. METHODS: In this case-controlled study of
      6,432 men the associations of risk factors with CKD and its risk of mortality
      were estimated using, primarily, logistic regression analysis. RESULTS: The 1,045
      (16.2%) patients with CKD stages 3-5 were older (72 +/- 10 vs. 59 +/- 13 years, P
      < 0.0001) with more hypertension (53.6 vs. 39.6%, P < 0.0001), diabetes (24.9 vs.
      19.8%, P < 0.0002), and CVD (35.3 vs. 17.8%, P < 0.0001) at baseline. Age > or
      =65 years (odds ratio [95% CI]) (4.95 [4.22-5.82]), hypertension (1.56 [1.34
      1.79]), diabetes mellitus (1.21 [1.03-1.43]), CVD (1.71 [1.47-2.00]), and White
      not Hispanic (1.57 [1.32-1.85]) were independently associated with CKD. The
      prevalence of CVD at baseline increased with decreasing renal function. Old age
      (1.98 [1.66-2.35]), CKD (1.94 [1.61-2.33], CVD (1.46 [1.23-1.74]) and tobacco use
      (1.91 [1.05-3.47]) were independently associated with the 750 (11.7%) deaths.
      CONCLUSION: Among veterans, traditional cardiovascular risk factors, CVD, and CKD
      are highly prevalent. CKD is associated with increased risk of baseline CVD and
      follow-up mortality.

PMID- 19117117
TI  - Melatonin prevents acetaminophen-induced nephrotoxicity in rats.
AB  - Nephrotoxicity is a major complication of acetaminophen (APAP), a widely used
      analgesic and antipyretic drug, and there is no specific treatment for APAP
      induced renal damage. It has been reported that reactive oxygen metabolites or
      free radicals are important mediators of APAP toxicity. In this study, the
      protective role of melatonin (MLT) on APAP-induced nephrotoxicity was
      investigated in rats. For this purpose, nephrotoxicity was induced in male Wistar
      albino rats by intraperitoneal (i.p.) administration of a single dose of 1,000
      mg/kg APAP. Some of these rats also received i.p. melatonin (10 mg/kg) 20 min
      after administration of APAP. The rats were sacrificed 24 h after administration
      of APAP. Urea and creatinine levels were measured in the blood, and levels of
      malondialdehyde (MDA) and glutathione (GSH), and glutathione peroxidase (GSH-Px),
      catalase (CAT), and superoxide dismutase (SOD) activity were determined in renal
      tissue. Serum urea and creatinine levels increased significantly as a result of
      APAP nephrotoxicity. A significant increase in MDA and decreases in GSH level and
      GSH-Px, CAT, and SOD activity indicated that APAP-induced renal damage was
      mediated through oxidative stress. Significant beneficial changes were noted in
      serum and tissue oxidative stress indicators in rats treated with MLT. These
      biochemical observations were supplemented by histopathological examination of
      kidney sections, which revealed that MLT also reduced the severity of APAP
      induced histological alterations in the kidney. These results indicate that
      administration of APAP causes oxidative stress to renal tissue and that MLT
      protects against the oxidative damage associated with APAP.

PMID- 19117118
TI  - Effects of conidia of various Aspergillus species on apoptosis of human
      pneumocytes and bronchial epithelial cells.
AB  - Aspergillus species can cause mycoses in human and animals. Previously, we
      demonstrated that A. fumigatus conidia from a human isolate inhibited apoptosis
      in human pneumocytes and bronchial epithelial cells. In the current study, we
      studied the effects of A. fumigatus conidia non-human origin and A. flavus, A.
      nidulans, A. niger and A. oryzae conidia on human cells apoptosis. Human
      pneumocytes or bronchial epithelial cells were simultaneously exposed to
      apoptotic inductors and aspergilli conidia. The cell cultures were analyzed by
      flow cytometry, immunoblotting, and examination of nuclear morphology. Similar to
      A. fumigatus conidia, A. flavus conidia inhibited cellular apoptosis while A.
      nidulans, A. niger and A. oryzae conidia did not affect apoptosis. We further
      studied the species specificity of conidia: there were no differences in the
      inhibition of apoptosis by A. fumigatus conidia from either human or bird
      isolates. In order to determine whether the inhibition of apoptosis by conidia is
      limited to certain strains, the effect on human cell apoptosis of different A.
      fumigatus human clinical isolates and A. fumigatus of environmental origin was
      evaluated. All A. fumigatus isolates inhibited apoptosis; an anti-apoptotic
      factor was released by conidia. For TNF-induced apoptosis, the anti-apoptotic
      effect of conidia of all isolates was found to be associated with a reduction of
      caspase-3 in human cells. The results suggest that suppression of apoptosis may
      play a role in reducing the efficacy of host defense mechanisms during infection
      with Aspergillus species.

PMID- 19117119
TI  - Applications of RNA interference in cancer therapeutics as a powerful tool for
      suppressing gene expression.
AB  - Cancer poses a tremendous therapeutic challenge worldwide, highlighting the
      critical need for developing novel therapeutics. A promising cancer treatment
      modality is gene therapy, which is a form of molecular medicine designed to
      introduce into target cells genetic material with therapeutic intent. The history
      of RNA interference (RNAi) has only a dozen years, however, further studies have
      revealed that it is a potent method of gene silencing that has developed rapidly
      over the past few years as a result of its extensive importance in the study of
      genetics, molecular biology and physiology. RNAi is a natural process by which
      small interfering RNA (siRNA) duplex directs sequence specific post
      transcriptional silencing of homologous genes by binding to its complementary
      mRNA and triggering its elimination. RNAi has been extensively used as a novel
      and effective gene silencing tool for the fundamental research of cancer
      therapeutics, and has displayed great potential in clinical treatment.

PMID- 19117121
TI  - Influence of preemptive analgesia on pulmonary function and complications for
      laparoscopic cholecystectomy.
AB  - Pain and diaphragmatic dysfunction are the major reasons for postoperative
      pulmonary complications after upper abdominal surgery. Preoperative
      administration of analgesics helps to reduce and prevent pain. The objective of
      this study was first to research the rate of pulmonary complications for
      laparoscopic cholecystectomy (LC) and then analyze the influence of preemptive
      analgesia on pulmonary functions and complications. Seventy patients scheduled
      for elective LC were included in our double-blind, randomized, placebo
      controlled, prospective study. Randomly, 35 patients received 1 g etofenamate
      (group 1) and 35 patients 0.9% saline (group 2) intramuscularly 1 h before
      surgery. All patients underwent physical examination, chest radiography, lung
      function tests, and pulse oxygen saturation measurements 2 h before surgery and
      postoperatively on day 2. Atelectasis was graded as micro, focal, segmental, or
      lobar. With preemptive analgesia, the need for postoperative analgesia decreased
      significantly in group 1. In both groups mean spirometric values were reduced
      significantly after the operation, but the difference and proportional change
      according to preoperative recordings were found to be similar [29.5 vs. 31.3%
      reduction in forced vital capacity (FVC) and 32.9 vs. 33.5% reduction in forced
      expiratory volume in 1 s (FEV(1)) for groups 1 and 2, respectively]. There was an
      insignificant drop in oxygen saturation rates for both groups. The overall
      incidence of atelectasia was similar for group 1 and 2 (30.2 vs. 29.2%). Although
      the degree of atelectesia was found to be more severe in the placebo group, the
      difference was not statistically significant. We concluded that although
      preemptive analgesia decreased the need for postoperative analgesia, this had no
      effect on pulmonary functions and pulmonary complications.

PMID- 19117122
TI  - Multiple tiny ectopic sebaceous glands discovered throughout entire esophageal
      tract.
AB  - A 45-year-old woman complaining of abdominal fullness was referred for endoscopic
      examination. She was a non-smoker and non-drinker. An endoscopic examination
      revealed the presence of more than 100 tiny, rounded, elevated, yellowish lesions
      <0.5 mm in diameter scattered throughout the upper and lower esophagus. Based on
      the endoscopic examination results, her stomach manifested symptoms of mildly
      superficial gastritis. Histopathologic examination of the esophagus biopsy
      specimen revealed that some of the lobules of the cells displayed typical
      sebaceous differentiation covered by a squamous epithelium. No evidence of
      inflammatory reaction, hair follicles, or malignancy was found. The patient's
      blood and serum findings were unremarkable. Our final diagnosis was multiple tiny
      ectopic sebaceous glands in the esophagus. This is an interesting and rare case
      of esophageal sebaceous glands distributed throughout the entire esophagus.
      Because there were no esophageal symptoms or/and eating problems, the patient did
      not require endoscopic surgery or other treatment. Follow-up examinations were
      recommended at intervals between 6 months and 1 year. At the 2-year follow-up, an
      endoscopic examination revealed no change in the size or the number of the tiny
      ectopic esophageal sebaceous glands.

PMID- 19117123
TI  - The influence of zinc supplementation on the pancreas of streptozotocin-diabetic
      rats.
AB  - The aim of this study was to investigate the effects of zinc supplementation on
      somatostatin and insulin peptide expressions and biochemical parameters. Six- to
      6.5-month-old female Swiss albino rats weighing 150-200 g were used. The animals
      were divided into four groups: group I: control (intact) animals; group II:
      control animals given zinc sulfate; group III: streptozotocin (STZ)- induced
      diabetic animals; group IV: STZ-induced diabetic animals given zinc sulfate.
      Fasting blood glucose and glutathione levels were measured at 0, 1, 30 and 60
      days. On day 60, the pancreas tissue and blood samples were taken from the
      animals. Zinc supplementation caused a decrease in hyperglycemia, as well as
      weight increase. Zinc sulfate treatment did not affect the number of somatostatin
      immunoreactive cells in the pancreas. More insulin-immunoreactive cells were
      observed in the pancreatic islets of the diabetic+zinc sulfate group than in the
      diabetic group, although it was not statistically significant. The results show
      that zinc supplementation may prevent diabetes in experimental animals.

PMID- 19117124
TI  - Pattern recognition scavenger receptors, SR-A and CD36, have an additive role in
      the development of colitis in mice.
AB  - The multifunctional pattern recognition scavenger receptors, SR-A and CD36, are
      predominantly expressed by lamina propria macrophages and considered important in
      innate immunity. We examined the role of these receptors in the pathophysiology
      of inflammatory bowel disease. Colitis was induced in wild type (WT), SRA(-/-),
      CD36(-/-), and SR-A/CD36 double deficient mice by administering DSS. DSS-induced
      moderately severe colitis in WT mice was manifested by weight loss, reduced
      hematocrit, and pathology. SR-A/CD36 double deficient mice developed
      significantly more severe colitis as indicated by anemia (P<0.01), decreased
      colonic length due to inflammation (P<0.01), and lesions when compared with WT
      and single deficient animals. Serum amyloid A was significantly more elevated in
      SR-A/CD36(-/-) mice (P<0.01) compared with WT and single deficient animals.
      However, the spleens of WT mice (P<0.05) were significantly enlarged.
      Inflammatory cytokine levels were considerably increased in WT mice (IL-6
      P<0.001, TNFalpha P<0.01). In contrast, SR-A deficient mice maintained more
      normal body and splenic weight and developed less severe colonic lesions compared
      to other groups. In conclusion, our data indicate that SR-A/CD36 double
      deficiency leads to more severe colonic lesions and dysregulated inflammatory
      response as compared with single SR-A or CD36 deficiency in colitis, suggesting
      additive effects between these two receptors in this model.

PMID- 19117125
TI  - The selective inhibition of type IV phosphodiesterase attenuates the severity of
      the acute pancreatitis in rats.
AB  - Phosphodiesterases (PDEs) are enzymes primarily responsible for regulation of the
      intracellular cyclic nucleotides. Among these enzymes, the type 4 PDE is highly
      expressed in most immune and inflammatory cells and its inhibition causes the
      suppression of immune and inflammatory cell activity, including production of
      cytokines. This study was designed to investigate the efficacy of the type 4 PDE
      inhibitor rolipram on acute pancreatitis in rats. Rats were divided into three
      groups--treatment, control, and sham. In the treatment and control groups, rats
      were pretreated with rolipram and vehicle before acute pancreatitis was induced.
      The pretreatment of rats with rolipram significantly reduced the amylase
      (P<0.0001) and IL-1beta levels (P=0.002) compared to vehicle treated rats. Also,
      mean histopathological scores were significantly reduced by rolipram treatment
      (P<0.005). It can be concluded that rolipram ameliorates severity of pancreatitis
      in rats.

PMID- 19117126
TI  - Factors associated with colon cancer stage at diagnosis.
AB  - We analyzed data from 1998-2004 from the National Cancer Data Base to evaluate
      associations between patient/treatment facility factors and stage at diagnosis
      for all colon cancers combined and by anatomic location. Compared to patients
      with private insurance, uninsured patients were significantly more likely to
      present with advanced-stage disease; Medicaid patients had likelihoods of
      advanced-stage colon cancer in-between those of privately insured and uninsured
      patients. Increased odds of advanced-stage colon cancer at diagnosis were also
      observed among Black (vs. White) patients, women (vs. men), and patients from low
      socioeconomic status (SES) regions (vs. those from higher SES regions). While the
      likelihood of advanced-stage disease at diagnosis decreased in later years
      overall, this decrease was not observed among patients with ascending colon
      cancers. Screening disparities may lead to more advanced stage at diagnosis among
      colon cancer patients; programs to improve access to screening among underserved
      populations may address this disparity.

PMID- 19117127
TI  - Identification of gene expression profiling in hepatocellular carcinoma using
      cDNA microarrays.
AB  - The aim of this study was systematic investigation of the differentially
      expressed genes during carcinogenesis in hepatocellular carcinoma (HCC) using
      cDNA microarray technology. The differentially expressed genes between 22 fresh
      HCC tissues and para-cancerous liver tissues (PCLT) were displayed using cDNA
      microarray technology. The result was verified by the reverse transcriptase
      polymerase chain reaction. Among the 8,464 human genes, 507 (5.99%) genes were
      expressed differentially at the mRNA levels between HCC and PCLT. Two hundred
      (2.36%) genes were down-regulated, whereas 307 (3.63%) genes were up-regulated.
      The mRNA expression levels of RhoC and protocadherin LKC detected by reverse
      transcription polymerase chain reaction (RT-PCR) were consistent with the
      microarray experiment. This study describes a gene expression profiling of HCC,
      which provides an extensive list of potential molecular markers for early
      diagnosis and molecular targets for the development of drugs to treat patients
      with primary HCC.

PMID- 19117128
TI  - Ultra-high performance liquid chromatography-mass spectrometry for the
      metabolomic analysis of urine in colorectal cancer.
AB  - We report here the results of a pilot study in which ultra-high performance
      liquid chromatography/time-of- flight-mass spectrometry (UPLC/TOF-MS) and
      multivariate statistical analysis (supervised partial least squares discriminant
      analysis, PLS-DA) were applied for urinary metabolite profiling and data
      interpretation. The results of the PLS-DA indicated that the metabolic pattern as
      a whole was significantly different between the groups of preoperative colorectal
      cancer (CRC) patients, postoperative CRC patients, and healthy volunteers,
      respectively. The preoperative group of patients showed significantly increased
      levels of low-molecular weight compounds (LMC) MW 283 and MW 234 in comparison to
      the group of healthy volunteers group. After the operation, the levels of these
      two LMC significantly decreased. These preliminary results suggest that the UPLC
      MS-based method coupled with pattern recognition will likely lead to procedures
      with the potential to be clinically applicable for the diagnosis of CRC and,
      consequently, to an improvement in patient prognosis.

PMID- 19117130
TI  - Still no meta-analysis of screening colonoscopy for colorectal cancer?

PMID- 19117129
TI  - Bedside sublingual video imaging of microcirculation in assessing bacterial
      infection in cirrhosis.
AB  - Bacterial infections are common in cirrhosis and can lead to life-threatening
      complications. Sidestream dark-field (SDF) imaging has recently emerged as a
      noninvasive tool for capturing real-time video images of sublingual
      microcirculation in critically ill patients with sepsis. The objective of this
      study was to assess the utility of SDF in determining underlying infection in
      patients with cirrhosis. Sublingual microcirculation was compared among patients
      with compensated cirrhosis (Group A, n=13), cirrhosis without sepsis (Group B,
      n=18), cirrhosis with sepsis (Group C, n=14), and sepsis only (Group D, n=10).
      The blood flow was semi-quantitatively evaluated in four equal quadrants in small
      (10-25 mm); medium (26-50 mm); and large (51-100 mm) sublingual capillaries. The
      blood flow was described as no flow (0), intermittent flow (1), sluggish flow
      (2), and continuous flow (3). The overall flow score or microvascular flow index
      (MFI) was measured for quantitative assessment of microcirculation and predicting
      power for concurrent infection in cirrhosis. Marked impairment was observed at
      all levels of microvasculature in Groups B and C when compared with Group A. This
      effect was restricted to small vessels only when Group B was compared with Group
      C. MFI<1.5 was found to have highest sensitivity (100%) and specificity (100%)
      for infection in decompensated cirrhosis. SDF imaging of sublingual
      microcirculation can be a useful bedside diagnostic tool to assess bacterial
      infection in cirrhosis.

PMID- 19117131
TI  - Survival differences by race/ethnicity and treatment for localized hepatocellular
      carcinoma within the United States.
AB  - Racial differences among hepatocellular carcinoma survival have been reported,
      but the etiology behind these disparities remains unclear. Using multi-variable
      logistic regression analysis, our restrospective cohort study investigated the
      demographic disparities in survival among localized hepatocellular carcinoma in
      the United States. From 1998 to 2001, 2,776 cases of localized hepatocellular
      carcinoma were identified. Significant racial/ethnic disparities in overall
      survival and utilization of therapies were identified. Compared with non-Hispanic
      white males, black females were 56% less likely to survive 3 years (OR 0.44; 95%
      CI 0.21-0.93). Treatment-specific models also demonstrated disparities, e.g.,
      compared with non-Hispanic whites, Asians receiving transplantation were 77% more
      likely to survive 3 years (OR, 1.77; 95% CI 1.28-2.44). There are significant
      racial/ethnic disparities in 3-year survival among patients with localized
      hepatocellular carcinoma. These differences are partially explained by
      demographic differences in utilization of therapy and in stage-specific survival
      for each therapy.

PMID- 19117132
TI  - Clinical significance of anti-HEV IgA in diagnosis of acute genotype 4 hepatitis
      E virus infection negative for anti-HEV IgM.
AB  - Anti-HEV IgM is a diagnostic for recent or ongoing HEV infection. However, some
      patients with acute hepatitis E (AHE) negative for anti-HEV IgM in acute period
      were often observed in clinical practice. In this study, we constructed the anti
      HEV IgA indirect ELISA assay to evaluate the significance of anti-HEV IgA. The
      specificity of anti-HEV IgA was 99.6%. Among 245 AHE patients, 84 samples from 84
      patients were positive for HEV RNA. The positive rate of anti-HEV IgA, anti-HEV
      IgM and anti-HEV IgG in 84 samples positive for HEV RNA was 96.3, 97.6, and
      88.1%, respectively, and no sample was negative for anti-HEV IgA and anti-HEV IgM
      simultaneously. Among 245 AHE patients, we found nine samples collected from nine
      patients in acute period were negative for anti-HEV IgM but positive for anti-HEV
      IgA and two samples were positive for HEV RNA. Detection of anti-HEV IgA can be a
      useful supplement for diagnosis of acute HEV infection especially in patients
      negative for anti-HEV IgM.

PMID- 19117133
TI  - Results of lateral internal sphincterotomy with open technique for chronic anal
      fissure: evaluation of complications, symptom relief, and incontinence with long
      term follow-up.
AB  - The aim of this study is to investigate the results of open lateral internal
      sphincterotomy (LIS) and the recurrence and incontinence rate, to perform a long
      term assessment of incontinence and to assess complications and relief of
      symptoms. This clinical prospective study was undertaken in patients undergoing
      open LIS. One hundred and twenty-nine patients entered the study. Mean duration
      of pain relief was 1.2 +/- 0.4 days and mean time before defecation without pain
      was 1.9 +/- 1.0 days. Complication rate was 41.8%. We found that urine retention
      was seen frequently in males. We demonstrated that open LIS up to the dentate
      line does not have a higher rate of incontinence. Incontinence after LIS was only
      to flatus and two-thirds of these resolved in 6 weeks. No patient showed
      improvement of incontinence after 6 weeks.

PMID- 19117134
TI  - Regional and foreign accent processing in English: can listeners adapt?
AB  - Recent data suggest that the first presentation of a foreign accent triggers a
      delay in word identification, followed by a subsequent adaptation. This study
      examines under what conditions the delay resumes to baseline level. The delay
      will be experimentally induced by the presentation of sentences spoken to
      listeners in a foreign or a regional accent as part of a lexical decision task
      for words placed at the end of sentences. Using a blocked design of accents
      presentation, Experiment 1 shows that accent changes cause a temporary
      perturbation in reaction times, followed by a smaller but long-lasting delay.
      Experiment 2 shows that the initial perturbation is dependent on participants'
      expectations about the task. Experiment 3 confirms that the subsequent long
      lasting delay in word identification does not habituate after repeated exposure
      to the same accent. Results suggest that comprehensibility of accented speech, as
      measured by reaction times, does not benefit from accent exposure, contrary to
      intelligibility.

PMID- 19117136
TI  - Nuclear receptors: one big family.
AB  - It is just over 20 years since the first steroid receptor cDNAs were cloned, a
      development that led to the birth of a superfamily of ligand activated
      transcription factors: the nuclear receptors. Natural ligands for nuclear
      receptors are generally lipophilic in nature and include steroid hormones, bile
      acids, fatty acids, thyroid hormones, certain vitamins and prostaglandins. These
      molecules act as sensors of the extracellular and intracellular environment and
      play crucial roles controlling development, differentiation, metabolic
      homeostasis, and reproduction. Since the original cloning experiments
      considerable progress has been made in our understanding of the structure,
      mechanisms of action and biology of this important family of proteins.

PMID- 19117137
TI  - Methods for measuring ligand dissociation and nuclear receptor turnover in whole
      cells.
AB  - Understanding the molecular mechanisms of steroid hormone action requires assays
      that measure rates of ligand dissociation and receptor degradation. Ligand
      dissociation is a pseudo-first order reaction of a high affinity [3H]-labeled
      ligand. Receptor turnover as described here is the rate of degradation of a
      radiolabeled receptor. The methods make use of transient expression of a nuclear
      receptor in cultured cells and are applicable to all nuclear receptors. Rates of
      ligand dissociation and receptor degradation provided the first insight into the
      interdomain interactions of the androgen receptor and the molecular basis for the
      phenotypic effects of naturally occurring androgen receptor loss-of-function
      germline mutations and gain-of-function somatic mutations, and for the potency
      differences between the biologically active androgens, testosterone, and
      dihydrotestosterone.

PMID- 19117135
TI  - Protein binding of antimicrobials: methods for quantification and for
      investigation of its impact on bacterial killing.
AB  - Plasma protein binding of antimicrobial agents is considered to be a key
      characteristic of antibiotics as it affects both their pharmacokinetics and
      pharmacodynamics. However, up to the present, no standard methods for measuring
      protein binding or for quantification of the influence of protein binding on
      antimicrobial activity exist. This short-coming has previously led to conflicting
      results on antibacterial activity of highly protein-bound antibiotics. The
      present review, therefore, set out to summarize (1) methods for quantification of
      protein binding, (2) microbiological growth media used for determination of the
      impact of protein binding on antimicrobial activity of antibiotics, and (3)
      different pharmacodynamic in vitro studies that are used in this context. The
      advantages and disadvantages of a wide range of different approaches are
      discussed and compared. The urgent call for international standardization by
      microbiological societies and laboratories may be considered as a logical
      consequence of the presented data.

PMID- 19117138
TI  - Flow cytometry as a tool for measurement of steroid hormone receptor protein
      expression in leukocytes.
AB  - Measurement of protein expression in live, intact cells using flow cytometry (FC)
      has been employed for several decades in the areas of immunology, cell biology,
      and molecular biology. More recently, this technique has found appreciation in
      applied scientific fields, including cancer biology and endocrinology, to serve
      as a tool for identifying cells more likely to respond to specific treatments.
      FC, also referred to as fluorescence-activated cell sorting (FACS), is an
      antibody-based method that provides the user with an ability to identify proteins
      expressed on surfaces of cells as well as in the cytoplasm, including steroid
      hormone receptors. This technique is most useful for examining specific cell
      types in a heterogeneous population and therefore can be used to identify cells
      more likely to respond to treatments based on expression of the appropriate
      receptor. Isolation of purified subpopulations for further manipulation and
      investigation of functional capacity is also possible using a cell sorter, which
      uses similar technology to isolate cells for use by the researcher. This is
      especially important for studying responses of less abundant cell populations in
      tissues that express high levels of a target protein or receptor of interest.
      Furthermore, FACS analysis is clinically useful to identify and isolate
      responsive cell populations, which may be less appreciable in whole tissues
      because of the diluting effects of surrounding, nonresponding cell types. Immune
      cells are commonly utilized as a source of cell populations in the FC technique
      and have previously been shown to express steroid hormone receptors and respond
      to steroid hormone treatment. Here, we demonstrate that FC is a useful tool for
      identifying immune cells expressing steroid hormone receptor protein. This method
      can also be easily expanded to include other, nonimmune cell populations to
      address specific research questions related to steroid hormone receptor biology.

PMID- 19117139
TI  - X-ray crystallography of agonist/antagonist-bound receptors.
AB  - Crystallographic analysis of the ligand-binding domains of nuclear hormone
      receptors (NR) has provided a unique insight into the molecular events that
      underlie the ligand-mediated control of their transcriptional activity. The
      technique relies on preparing milligram quantities of protein, growing three
      dimensional crystals of the desired protein-ligand complex, collecting X-ray
      diffraction data, and subsequently interpreting the derived electron density maps
      to reveal the structure of the complex.

PMID- 19117140
TI  - FRAP and FRET methods to study nuclear receptors in living cells.
AB  - Quantitative imaging techniques of fluorescently-tagged proteins have been
      instrumental in the study of the behavior of nuclear receptors (NRs) and
      coregulators in living cells. Ligand-activated NRs exert their function in
      transcription regulation by binding to specific response elements in promotor and
      enhancer sequences of genes. Fluorescence recovery after photobleaching (FRAP)
      has proven to be a powerful tool to study the mobility of fluorescently-labeled
      molecules in living cells. Since binding to DNA leads to the immobilization of
      DNA-interacting proteins like NRs, FRAP is especially useful for determining DNA
      binding kinetics of these proteins. The coordinated interaction of NRs with
      promoters/enhancers and subsequent transcription activation is not only regulated
      by ligand but also by interactions with sets of cofactors and, at least in the
      case of the androgen receptor (AR), by dimerization and interdomain interactions.
      In living cells, these interactions can be studied by fluorescence resonance
      energy transfer (FRET). Here we provide and discuss detailed protocols for FRAP
      and FRET procedures to study the behavior of nuclear receptors in living cells.
      On the basis of our studies of the AR, we provide protocols for two different
      FRAP methods (strip-FRAP and FLIP-FRAP) to quantitatively investigate DNA
      interactions and for two different FRET approaches, ratio imaging, and acceptor
      photobleaching FRET to study AR domain interactions and interactions with
      cofactor motifs. Finally, we provide a protocol of a technique where FRAP and
      acceptor photobleaching FRET are combined to study the dynamics of interacting
      ARs.

PMID- 19117141
TI  - Receptor-DNA interactions: EMSA and footprinting.
AB  - Defining the precise promoter DNA sequence motifs where nuclear receptors and
      other transcription factors bind is an essential prerequisite for understanding
      how these proteins modulate the expression of their specific target genes. The
      purpose of this chapter is to provide the reader with a detailed guide with
      respect to the materials and the key methods required to perform this type of DNA
      binding analysis. Irrespective of whether starting with purified DNA-binding
      proteins or somewhat crude cellular extracts, the tried-and-true procedures
      described here will enable one to accurately access the capacity of specific
      proteins to bind to DNA as well as to determine the exact sequences and DNA
      contact nucleotides involved. For illustrative purposes, we primarily have used
      the interaction of the androgen receptor with the rat probasin proximal promoter
      as our model system.

PMID- 19117142
TI  - Chromatin immunoprecipitation (ChIP) methodology and readouts.
AB  - The identification of direct nuclear hormone receptor gene targets provides clues
      to their contribution to both development and cancer progression. Until recently,
      the identification of such direct target genes has relied on a combination of
      expression analysis and in silico searches for consensus binding motifs in gene
      promoters. Consensus binding motifs for transcription factors are often defined
      using in vitro DNA binding strategies. Such in vitro strategies fail to account
      for the many factors that contribute significantly to target selection by
      transcription factors in cells beyond the recognition of these short consensus
      DNA sequences. These factors include DNA methylation, chromatin structure,
      posttranslational modifications of transcription factors, and the cooperative
      recruitment of transcription factor complexes. Chromatin immunoprecipitation
      (ChIP) provides a means of isolating transcription factor complexes in the
      context of endogenous chromatin, allowing the identification of direct
      transcription factor targets. ChIP can be combined with site-specific PCR for
      candidate binding sites or alternatively with cloning, genomic microarrays or
      more recently direct high throughput sequencing to identify novel genomic
      targets. The application of ChIP-based approaches has redefined consensus binding
      motifs for transcription factors and provided important insights into
      transcription factor biology.

PMID- 19117143
TI  - Yeast-based reporter assays for the functional characterization of cochaperone
      interactions with steroid hormone receptors.
AB  - Steroid hormone receptor-mediated reporter assays in the budding yeast
      Saccharomyces cerevisiae have been an invaluable tool for the identification and
      functional characterization of steroid hormone receptor-associated chaperones and
      cochaperones. This chapter describes a hormone-inducible androgen receptor
      mediated beta-galactosidase reporter assay in yeast. In addition, the
      immunophilin FKBP52 is used as a specific example of a receptor-associated
      cochaperone that acts as a positive regulator of receptor function. With the
      right combination of receptor and cochaperone expression plasmids, reporter
      plasmid, and ligand, the assay protocol described here could be used to
      functionally characterize a wide variety of nuclear receptor-cochaperone
      interactions. In addition to the functional characterization of receptor
      regulatory proteins, a modified version of this assay is currently being used to
      screen compound libraries for selective FKBP52 inhibitors that represent
      attractive therapeutic candidates for the treatment of steroid hormone receptor
      associated diseases.

PMID- 19117144
TI  - High throughput analysis of nuclear receptor-cofactor interactions.
AB  - Various assays have been employed to study the nuclear receptor/cofactor
      interactions. Coimmunoprecipitation protocols, both yeast and mammalian two
      hybrid systems, and electrophoretic mobility shift/supershift assays are all
      commonly used. One of the most useful assays for studying direct protein-protein
      interactions is the glutathione-S-transferase "pulldown" assay. We have developed
      a high-throughput version of this assay that utilizes a filter microplate to
      allow parallel processing of many samples, significantly reducing the time and
      reagents required for the assay and increasing the sensitivity of the assay for
      weaker protein-protein interactions.

PMID- 19117145
TI  - Binding affinity and kinetic analysis of nuclear receptor/co-regulator
      interactions using surface plasmon resonance.
AB  - Knowledge of the kinetics of protein-protein interactions has become important in
      defining nuclear receptor function. Such knowledge allows characterization of
      interactions that occur with high affinity and/or selectivity. Surface plasmon
      resonance is a useful and sensitive tool for studying protein-protein
      interactions. This technique involves immobilization of a "ligand" to the surface
      of a sensor chip and subsequently passing over multiple concentrations of
      "analyte" to generate binding curves. Interaction between the receptor and target
      protein is monitored by the density at the sensor chip surface and allows
      calculation of the association and dissociation stages (and therefore affinity)
      of interactions to be assessed in real-time. Using software packages, these
      kinetic parameters can be quantified. Importantly, the levels of recombinant
      protein required are much less than that needed for other affinity techniques
      such as isothermal titration calorimetry and anisotropy fluorescence
      spectroscopy.

PMID- 19117146
TI  - Using RNA interference to study protein function.
AB  - RNA interference can be extremely useful in determining the function of an
      endogenously-expressed protein in its normal cellular environment. In this
      chapter, we describe a method that uses small interfering RNA (siRNA) to knock
      down mRNA and protein expression in cultured cells so that the effect of a
      putative regulatory protein on gene expression can be delineated. Methods of
      assessing the effectiveness of the siRNA procedure using real time quantitative
      PCR and Western analysis are also included.

PMID- 19117148
TI  - Development of phosphorylation site-specific antibodies to nuclear receptors.
AB  - Protein phosphorylation is a versatile posttranslational modification that can
      regulate nuclear receptor function. Although the precise role of receptor
      phosphorylation is not fully understood, it appears that it functions to direct
      or refine receptor activity in response to particular physiological requirements.
      Identifying and characterizing specific nuclear receptor phosphorylation sites is
      an important step in elucidating the role(s) receptor phosphorylation plays in
      function. Although traditional methods of metabolic labeling and in vitro protein
      phosphorylation have been informative, receptor phosphorylation site-specific
      antibodies are simple and reliable tools to study receptor phosphorylation. This
      chapter will discuss how to develop nuclear receptor phosphorylation site
      specific antibodies to elucidate function.

PMID- 19117147
TI  - Using intrinsic fluorescence emission spectroscopy to study steroid receptor and
      coactivator protein conformation dynamics.
AB  - X-ray crystallography and nuclear magnetic resonance (NMR) spectroscopy have
      proved powerful methods for studying the structure of the isolated ligand and DNA
      binding domains of nuclear receptors. However, the N-terminal domain (NTD), which
      in some members of the superfamily is important for transcriptional regulation,
      and the full-length receptor proteins have proved more challenging. The NTD of
      different nuclear receptors show little sequence homology and can vary
      dramatically in length from a few to several hundred amino acids. Low resolution
      structural analysis using circular dichroism, NMR, steady-state fluorescence
      spectroscopy, and Fourier transformed infrared spectroscopy has provided valuable
      information on the conformation and folding of the structurally plastic NTD. In
      this chapter, we discuss protocols for measuring the intrinsic fluorescence
      emission spectrum for tryptophan residues under different experimental conditions
      of protein folding and unfolding.

PMID- 19117149
TI  - Tissue-selective knockouts of steroid receptors: a novel paradigm in the study of
      steroid action.
AB  - The use of tissue-selective rather than ubiquitous knockouts of steroid receptors
      allows a more refined study of the mechanism of steroid action in defined target
      tissues and circumvents problems such as early lethality or major developmental
      defects precluding studies in affected organs. In this chapter, we describe the
      main steps involved in the development of tissue-selective steroid receptor
      knockouts by Cre/loxP technology. Problems in the development of a mouse strain
      with a floxed receptor allele, the selection of a suitable Cre expressing mouse
      strain, the generation of cell-selective knockouts by crossbreeding of the
      mentioned mouse strains, and the control of appropriate receptor inactivation are
      discussed taking the generation of mice with a Sertoli cell-selective ablation of
      the androgen receptor as an example.

PMID- 19117150
TI  - Methods for identifying and studying genetic alterations in hormone-dependent
      cancers.
AB  - Genetic alterations underlying the development of cancer include large
      chromosomal aberrations, such as amplifications, deletions and translocations as
      well as small changes in sequence, i.e. mutations. Thus, different methods are
      needed to reveal various types of genetic changes. Fluorescence in situ
      hybridisation (FISH) is a versatile technique for detecting chromosomal
      alterations either in cultured cells or even in formalin-fixed paraffin-embedded
      tissue. For screening mutations, denaturing high-performance liquid
      chromatography (DHPLC) provides a relatively fast, cheap and sensitive option.
      The only special requirement is the HPLC equipment suitable for the analysis. As
      a screening tool, it does not reveal the actual base pair change, which in the
      end needs to be done by sequencing. FISH and DHPLC can both be utilized in
      research as well as in clinical diagnostic laboratories.

PMID- 19117151
TI  - [Non-opioid and opioid medication in neuropathic pain].
AB  - Treatment of neuropathic pain is difficult despite new treatments and there is no
      single treatment that Works for all conditions and their underlying mechanisms.
      Given the increasing evidence for effective treatments of neuropathic pain, it is
      important for the clinician to know which drugs are most effective neuropathic
      pain relieving pain and associated with the fewest adverse effects and there is a
      need for an evidence-based algorithm to treat neuropathic pain conditions.
      Ideally, the evidence for the non-opioids and opioids choices in such an
      algorithm would be based on direct comparisons of one drug with another, for both
      efficacy and side effects. There are very few such direct comparisons available.

PMID- 19117152
TI  - [Comparison of analgesic activity of intraarticular lornoxicam, bupivacaine and
      saline after knee arthroscopy].
AB  - Postoperative pain is an important parameter in discharge and rehabilitation in
      daycase arthroscopic knee surgery. This study compared the efficacy of
      intraarticular application of lornoxicam, bupivacaine and placebo on
      postoperative pain after arthroscopic knee surgery. With the approval of the
      local ethics committee and informed consent of the patients, 90 patients (ASA
      score I-II), aged between 18-65 years undergoing arthroscopic meniscectomy were
      included in this randomized, blinded, prospective study and were divided into
      three groups (30 patients each): 8 mg lornoxicam was applied to Group L (GL), 50
      mg bupivacaine to Group B (GB) and normal saline to Group S (GS) in 20 mL volume
      intraarticularly. Postoperative analgesia was maintained by intravenous tramadol
      HCl 50 mg/h at the first 4 h and then paracetamol 500 mg plus codeine 7.5 mg
      preparation as needed. The numeric rating scale (NRS) values were evaluated at
      rest and at active-passive motion at 4, 12, 24 and 48 h, total analgesic
      consumption were recorded. There were statistically significant differences
      between GS and GL and GS and GB in term of tramadol consumption (p < 0.05 and p <
      0.05). The analgesiconsumption of GL patients at the end of 48 h were lower than
      GB and GS (p < 0.001 and p < 0.05). The NRS values of GL were always lower than
      the other groups with statistical significance at certain times. We concluded
      that intraarticular lornoxicam provided better pain control than bupivacaine and
      saline in arthroscopic knee surgery.

PMID- 19117153
TI  - [The effect of three different lornoxicam administrations on postoperative
      analgesia].
AB  - In this study we evaluated the postoperative analgesic efficacy of lornoxicam PO,
      IM and IV administration preoperatively. Fourty patients, aged between 18-65
      years, ASA I-II class, were randomized to four groups. Lornoxicam 8 mg was
      administired PO, IM, IV (Group PO, Group IM, Group IV) 1 hour before the
      operation. Analgesia was not performed in control group (Group C). First
      analgesic requirement time, analgesic consumption and the VAS and VRS pain scores
      were recorded postoperatively. When VAS 3 patient controlled analgesia with
      lornoxicam was begun. We found that first analgesic requirement time was shorter,
      postoperative 2nd hour VAS and VRS scores and drug consumptions were higher in
      Grup C cases according to the other groups. There was no significant difference
      in first analgesic requirement time and analgesic consumption. Preoperative
      administration of 8 mg lornoxicam delayed the first analgesic requirement time
      and decreased total analgesic requirement. There was no difference on analgesic
      effect between PO, IM, and IV administrations.

PMID- 19117154
TI  - Comparison of epidural ropivacaine 0.2% and ropivacaine 0.2% in combination with
      sufentanil 0.75 microg mL-1 for postcaesarean analgesia.
AB  - Analgesic techniques after c-section must be effective producing early
      mobilisation to enable mothers to care effort their babies. In this study, the
      comparison of ropivacaine 0.2% alone, with ropivacaine 0.2%+sufentanil 0.75
      microg mL-1 for patient controlled epidural analgesia (PCEA) was aimed. Fifty
      women (ASA-I) were enrolled in the study. All patients had combined spinal
      epidural anaesthesia. Infusion of analgesic solutions was started when sensory
      level decreased by two dermatome levels. The patients randomly assigned, into two
      groups (n=25). In Group-I, ropivacaine 0.2% and sufentanil 0.75 microg mL-1, in
      Group-II, ropivacaine 0.2% alone were applied (bolus 1.25 mL, lockout 30 min,
      with 2.5 mL h-1 background infusion). Pain (Visual Analog Scale), motor blockage
      (Bromage scale) and sedation (Four point scale) were evaluated during 24 hours
      after Caesarean, using the scales of visual analogue, bromage, and four-point,
      respectively. Haemodynamic and respiratory parameters, side effects, total drug
      consumption and additional analgesic need, were recorded. Statistical analysis
      included student-t, chi-square, and Mann Whitney U tests. There was no difference
      in demographic data, sedation scores, haemodynamic and respiratory parameters,
      between the groups. Motor block and pain scores were significantly higher in
      Group-II than in Group-I at 2 and 4. h. Total drug consumption was 65.24+/-4.20
      mL for Group-I and 81.1+/-6.44 mL for Group-II, (P<0.05). Four patients in Group
      I and 21 patients in Group-II received additional analgesic. Pruritus was
      observed more frequently in Group-I. The addition of sufentanil 0.75 microg mL-1
      to ropivacaine 0.2% for PCEA after Caesarean led to more effective analgesia and
      less motor weakness when compared to ropivacaine 0.2% alone, especially during
      early postoperative period.

PMID- 19117155
TI  - [Pain treatment practice according to the WHO analgesic ladder in cancer
      patients: eight years experience of a single center].
AB  - In this study we evaluated the results of pain treatment practices according to
      the World Health Organization analgesic ladder treatment. and other treatment
      modalities in cancer patients who were admitted to an anesthesiology-based pain
      service. Patient characteristics, distribution of the patients according to the
      primary pathologic sites, initial and last distribution of the patients according
      to analgesic ladder treatment, other invasive or non-invasive treatment
      modalities, side effects, and other data related with the patients were examined.
      416 of 475 (87.5%) patients were treated using the WHO analgesic ladder
      treatment, 57 patients (12 %) were treated by invasive techniques. The number of
      successfully treated patients in step I, II and III were 49 (11.77%), 307
      (73.79%) and 60 (14.42) respectively. 181 of 416 (43.50%) patients used
      anticonvulsants or neuroleptics, 341 of 416 (81.97%) patients used
      antidepressants. In 31 of 416 patients (7.5%), non-invasive or invasive treatment
      modalities had become necessary to augment the WHO analgesic ladder treatment.
      Over the entire treatment period, side effects were reported in 17.05% of the
      patients. The follow-up time for the patients was 42 +/- 109.7 days, the mean
      interview number was 5.6+/-7.6, the longest follow-up time was 1380 days, and the
      maximum number of the interviews made by the same patient was 68. In conclusion,
      we think that, using the World Health Organization analgesic ladder treatment and
      administering appropriate analgesics and adjuvants in appropriate oral doses
      determined for appropriate subjects could successfully treat a great number of
      these patients.

PMID- 19117156
TI  - A case of Horner's syndrome following lateral sagittal infraclavicular block.
AB  - Horner's Syndrome results from paralysis of the ipsilateral sympathetic cervical
      chain (stellate ganglion) caused by surgery, drugs (mainly high concentrations of
      local anesthetics), local compression (hematoma or tumor), or inadequate
      perioperative positioning of the patient. It occurs in 100 % of the patients with
      an interscalene block of the brachial plexus and can also occur in patients with
      other types of supraclavicular blocks. Horner's syndrome may be described as an
      unpleasant side effect because it has no clinical consequences in itself. For
      this reason anesthesiologists should be aware of this syndrome and if it occurs
      patients should be reassured and monitored closely. In this case report, we
      presented a case of Horner's Syndrome following lateral sagittal infraclavicular
      block (LSIB), a newly described technique.

PMID- 19117157
TI  - Caudal epidural anesthesia for a 2-year old child with congenital myasthenia
      gravis.
AB  - Myasthenia gravis is an autoimmune disease with antibodies directed against the
      acetylcholine receptor at the neuromuscular junction. Anesthetists have a special
      interest in myasthenia gravis because of its interaction with various anesthetic
      agents. Unlike adult myasthenic patients; very little report has been written
      about the anesthetic management in children, other than in relation to
      thymectomy. Although the use of caudal anesthesia in pediatric patients is
      common, have not seen any report concerning its use in a myasthenic child. In
      this case report, we represented a 2 year-old boy was performed caudal anesthesia
      for orchiopexy operation. He had presented difficulty in breathing, generalized
      weakness and droopy eyes due to congenital myasthenia gravis. In the operating
      room, following the routine monitoring, the patient was sedated with intravenous
      1mg midazolam and 10 mg ketamine. Then caudal block was performed. 17 minutes
      later from the local anesthetic injection; operation was started and lasted 45
      minutes. The patient did not require intraoperative supplemental analgesia and
      postoperative course was uneventful. Specific attention should be paid to
      voluntary and respiratory muscle strength in myasthenia gravis patients. Caudal
      anesthesia allowed airway control of myasthenia gravis patients without
      endotracheal intubations and muscle relaxant. In conclusion, we think that caudal
      anesthetic technique may be considered as a safe and suitable for the myasthenic
      child and it may represent a valid alternative to general anesthesia for these
      patients.

PMID- 19117158
TI  - Digital volume tomography (DVT) as a diagnostic modality of the anterior skull
      base.
AB  - CONCLUSION: Because of high resolution and the relatively lower costs in
      comparison with modern helical CT scanners, digital volume tomography (DVT) can
      be recommended in the diagnosis of the nasal cavity and paranasal sinuses.
      OBJECTIVES: DVT is an advancement of panoramic tomography and is based on the
      principles of rotational tomography. It enables high resolution visualization of
      osseous structures. The slices can be displayed in three orthogonal planes that
      can be changed in angle arbitrarily. Data volumes of up to 12*17 cm can be
      examined with a new generation of the DVT. The aim of this study was to point out
      the potential of DVT in the anterior skull base. SUBJECTS AND METHODS: DVT scans
      with a cylindrical size of 10 cm in diameter and 10 cm in height were performed
      in 23 patients. The identification of surgical key landmarks (uncinate process,
      middle turbinate, ethmoidal bulla, agger nasi cells, Haller cells, frontal
      recess, anterior ethmoidal artery in its relationship to the skull base, the
      cribiform plate of the sphenoidal sinus in relation to the optic nerve, and the
      internal carotid artery) was evaluated. RESULTS: Display of the essential
      surgical key landmarks was possible in all patients.

PMID- 19117159
TI  - An animal model of central auditory pathway imaging in the rat brain by high
      resolution small animal positron emission tomography.
AB  - CONCLUSIONS: Our study demonstrated that high resolution animal positron emission
      tomography (PET) can non-invasively assess the change in glucose metabolism of
      the central auditory pathway including the inferior colliculus and auditory
      cortex in the rat. OBJECTIVES: The traditional in vitro approach with
      immunohistochemical staining or autoradiography to assess chronological changes
      or topographic arrangement of central auditory pathway required sacrificing a
      large number of animals. Inter-individual difference is also a major concern.
      Therefore, development of an in vivo animal model using PET imaging would be a
      rational method to overcome these shortcomings. MATERIALS AND METHODS: Small
      animal PET scan using (18)F-fluorodeoxyglucose (FDG) as a functional marker was
      performed in rats. Each animal was serially scanned before and after unilateral
      cochlear ablation, with and without acoustic stimulation. The images were
      analyzed by the region of interest (ROI) method. Ratios of radioactivity at the
      inferior colliculus and auditory cortex and a referenced cerebral cortex between
      bilateral hemispheres were measured. RESULTS: These scans demonstrated several
      brain structures including the inferior colliculus (IC) and cortex (B). Moreover,
      unilateral cochlear ablation decreased the radioactivity at contralateral IC and
      auditory cortex (C) areas. Differences may reach 33% in IC and 27% in C, and
      average radioactivity ratios were 1.24+/-0.08 and 1.18+/-0.07 in selected
      adjacent sections, respectively.

PMID- 19117161
TI  - Ossiculoplasty with intact stapes: analysis of hearing results according to the
      middle ear risk index.
AB  - CONCLUSIONS: In ossiculoplasty with intact stapes, using autologous incus, cortex
      bone chips and plastipore partial ossicular reconstruction prostheses,
      improvement in hearing was nearly equal. In patients who had mild risk scores,
      the incus had better gain values compared with patients who had severe scores.
      OBJECTIVE: We aimed to prove the utility of the middle ear risk index score and
      its predictive value in hearing outcome. We also evaluated hearing results for
      different reconstruction materials. PATIENTS AND METHODS: This was a
      retrospective chart review of 189 patients who had ossiculoplasty with intact
      stapes using autologous incus, cortex bone chips and plastipore partial ossicular
      reconstruction prostheses. Hearing outcomes and the average improvement in
      hearing with different reconstruction materials were analysed by using middle ear
      risk index scores. RESULTS: The average hearing improvements for incus, cortex
      and partial ossicular reconstruction prostheses were 12.77+/-14.58 (p<0.001),
      12.34+/-15.98 (p=0.005) and 14.10+/-13.87 dB (p<0.001), respectively. The
      postoperative air-bone gap levels were 20.42+/-14.54 dB in incus, 17.33+/-16.86
      dB in cortex and 17.59+/-11.66 dB in partial ossicular reconstruction prostheses.
      When the preoperative middle ear risk index scores and postoperative air-bone gap
      and gain values were compared, in the incus group, statistically significant
      associations were demonstrated between scores and hearing outcomes (p=0.009).

PMID- 19117169
TI  - Experimental evidence suggestive of early intervention in mucoid otitis media.
AB  - CONCLUSIONS: Mucoid effusion can undergo a process of organization related to the
      inflammatory process and hypoventilation; organized effusion in the presence of
      epithelial breaks is a potential source for formation of granulation tissue and
      cholesterol granuloma within 3 months of evolution. OBJECTIVES: The aim of this
      study was to investigate the evolution of mucoid otitis media and its
      relationship with the organized effusion within a time-span of 3 months.
      MATERIALS AND METHODS: Two groups of animals were selected. In group I, 15
      chinchillas had a chemically modified bovine collagen type 2 gelatin membrane
      placed through a mechanically induced tympanic membrane perforation, bridging the
      external auditory canal and the promontory. In group II, 75 cats underwent
      eustachian tube obstruction with soft grade silastic sponges. Experimental phases
      and animal sacrifices were performed under general anesthesia. After sacrifice,
      temporal bones were prepared, stained with hematoxylin and eosin and evaluated
      under light microscopy. RESULTS: The experimental ears in both groups were
      observed to undergo gradual pathological changes with increasing survival times.
      The acute inflammatory phase turned into chronic irreversible changes, which
      correlated directly with the initial amount of effusion and the areas of
      epithelial breaks, granulation tissue, cholesterol granuloma, and epithelial
      migration.

PMID- 19117170
TI  - Simultaneous and non-simultaneous dual electrode stimulation in cochlear
      implants: evidence for two neural response modalities.
AB  - CONCLUSION: There are two modalities of dual electrode stimulation: a shifting,
      continuous excitation, which is the desired effect, and a split excitation with
      considerable variation in loudness. The first one most likely occurs in the basal
      turn, with adjacent contacts, stimulated simultaneously rather than sequentially.
      OBJECTIVES: This study examines the effects on place pitch and loudness of
      simultaneous current steering and sequential stimulation. These can give cochlear
      implant patients access to more perceptual channels than physical contacts in the
      electrode array. MATERIALS AND METHODS: For both lateral wall and perimodiolar
      electrodes, simultaneous current steering as well as sequential stimulation,
      place pitch and loudness of the percept were predicted with a computational model
      of the implanted human cochlea. The loudness predictions were validated with
      psychophysical loudness balancing experiments. RESULTS: Simultaneous stimulation
      with adjacent electrode contacts in the basal end of the cochlea was generally
      able to produce a single, gradually shifting intermediate pitch percept.
      Simultaneous stimulation beyond the first cochlear turn, sequential stimulation
      and simultaneous stimulation with non-adjacent electrode contacts often produced
      two regions of excitation. In the case of sequential stimulation the total amount
      of current to reach most comfortable loudness was raised, both in the model and
      in the patients.

PMID- 19117172
TI  - Totally implantable middle ear device for rehabilitation of sensorineural hearing
      loss: preliminary experience with the Esteem, Envoy.
AB  - CONCLUSION: According to the first series of implanted patients, Esteem 2
      technology can be regarded as a safe and reliable system for hearing restoration
      in case of moderate to severe sensorineural hearing loss. OBJECTIVES: To assess
      the benefit deriving from implantation of a totally implantable middle ear device
      in subjects affected by moderate to severe sensorineural hearing loss, the Esteem
      2 (Envoy Medical), as measured through pure tone audiometry testing carried out
      during the different postoperative fitting sessions. PATIENTS AND METHODS: Six
      patients have been operated on since July 2007. Selection was carried out via
      preoperative audiometric tests and thorough counseling, which considered
      information on previous experience with conventional hearing aids as well as each
      patient's motivation to undergo a surgical application. Specific surgical
      training is needed to accommodate routine surgical steps along with less familiar
      steps, such as placement of cement material and overall fixation of the system.
      RESULTS: The surgical procedure took a long time, but a reduced duration was
      recorded in the last procedure compared with the first one. The implantation
      process induced a deterioration in hearing thresholds, which fully recovered
      after activation of the device. A postoperative hearing gain could be measured in
      all three patients: in this regard, the perceived quality of sound was shown to
      be better than could be expected by the measurable hearing gain.

PMID- 19117173
TI  - Stem cell transplantation in autoimmune diseases. Foreword.

PMID- 19117174
TI  - Current perspectives of autologous stem cell transplantation for severe Juvenile
      Idiopathic Arthritis.
AB  - The majority of children with Juvenile Idiopathic Arthritis can nowadays be
      treated adequately. However despite the use of combinations of antirheumatic
      drugs, corticosteroids and the newer so called biologicals (blocking the TNF,
      Interleukin 1 or Interleukin 6 pathways) a proportion of children with arthritis
      remain resistant also to these therapies and suffer from a very severe,
      debilitating and potentially fatal disease. For such children autologous stem
      cell transplantation (ASCT) is successfully performed since 1997. Here we
      describe the long term outcome of the initial cohort of children with resistant
      Juvenile Idiopathic arthritis, treated with ASCT. The initial cohort of children
      was treated with a conditioning regimen containing Cyclophosphamide, anti
      thymocyte globulins and low dose Total Body irradiation. Overall favourable
      responses were seen, with a drug free remission rate of 50-55 %. In the more
      recent years late relapses were noted with lower percentages for drug free long
      term outcome. Special emphasis is given on 2 cases showing very late relapses,
      occurring after 7 and 9 years. The observed relapses are often less severe
      compared to the situation before SCT and can be treated successfully with
      conventional drugs in the majority of cases. More recently, ASCT was performed in
      4 JIA children with a fludarabin containing regimen in stead of low dose TBI.
      With a 4 to 5 year follow up, these 4 patients are all in drug free full
      remission. Allogeneic transplant with an HLA matched family donor was reported in
      2 JIA cases. Follow up of 1 and 3 year is sofar show clinical disease remission
      and tapering of medition. In conclusion, given the favourable long term outcome,
      SCT remains a valuable treatment option for children with drug resistant JIA.

PMID- 19117177
TI  - The validity of the Color Trail Test in the pre-driver assessment of individuals
      with acquired brain injury.
AB  - PRIMARY OBJECTIVE: To examine the validity of the Color Trails Test (CTT), a
      culture- fair analogue of the Trails Test, in the pre-driver assessment of
      individuals with acquired brain injury (ABI). RESEARCH DESIGN: Retrospective
      study. METHODS AND PROCEDURES: 30 participants with ABI completed the CTT and
      Useful Field of View (UFOV) in a driving rehabilitation clinic. Within the same
      week an on-road evaluation was conducted by a driving rehabilitation specialist,
      and a driving instructor. RESULTS: 50% of the participants passed the on-road
      evaluation and 50% failed. Individuals who passed the on-road test performed the
      CTT1 and CTT2 faster than those who failed, however the difference between the
      pass/fail groups was significant only for the CTT1. A correlation analysis
      between the CTT subtests (CTT1 and CTT2) and the UFOV subtests revealed
      significant, moderate correlations between these measures. CONCLUSIONS: The CTT1
      may contribute to the pre-driving screening by rapidly identifying those
      individuals who are most at risk for unsafe driving behaviors. Further studies
      are required with a larger representative sample.

PMID- 19117178
TI  - A biopsychosocial perspective of aggression in the context of traumatic brain
      injury.
AB  - PRIMARY OBJECTIVE: The aim of this study was to explore the factors associated
      with aggression in the traumatic brain injury population. The focus of the study
      was to evaluate the (a) frequency and severity of aggressive behaviours in
      outpatients with traumatic brain injury (TBI), (b) ecological validity of the
      Ruff Neurobehavioral Inventory (RNBI) Anger scale, and (c) comorbid and pre
      morbid factors associated with aggression in patients with TBIs. RESEARCH DESIGN:
      A multi-group comparative research design was employed. METHODS AND PROCEDURE: An
      outpatient sample of 67 patients with TBIs using the RNBI and clinical
      interviews. MAIN OUTCOMES AND RESULTS: Based on clinical ratings, 25% endorsed no
      aggression, 38% reported mild aggression and 37% reported moderate-to-severe
      aggression, which was validated with the RNBI Anger post-morbid scale. A MANOVA
      found that none of the pre-morbid RNBI scales were significantly elevated across
      the anger groups; however, pre-post-morbid differences between the groups were
      found. A principle component analysis showed three main domains: 'physical,
      cognitive and emotional' that related to elevated post-morbid anger. CONCLUSIONS:
      A biopsychosocial model of post-morbid aggression is proposed to advance both the
      diagnosis and treatment of patients with TBIs who experience elevated anger.

PMID- 19117179
TI  - The Modified Tardieu Scale for the measurement of elbow flexor spasticity in
      adult patients with hemiplegia.
AB  - PRIMARY OBJECTIVE: To investigate the inter-rater reliability of the Modified
      Tardieu Scale (MTS) in the measurement of elbow flexor muscle spasticity in
      patients with adult hemiplegia. RESEARCH DESIGN: A cross-sectional study to
      examine the agreement between two raters on elbow flexor muscle spasticity using
      Modified Tardieu Scale. INTERVENTIONS: Not applicable. METHODS AND PROCEDURES:
      Thirty patients (21 men, nine women) with an age range of 21-79 years (mean =
      54.9; SD = 15.7) were tested. Two inexperienced raters assessed the elbow flexor
      muscle spasticity in the affected side during the same session. The order of
      assessments by the two raters was randomized. The main outcome measure was
      dynamic component of spasticity (R2-R1). Reliability was also calculated for MTS
      scores, angle of muscle reaction (R1), and passive range of motion (R2). MAIN
      OUTCOMES AND RESULTS: The ICC for R2-R1 was 0.72. The ICC for MTS scores, R1 and
      R2 were 0.74, 0.74 and 0.56, respectively. CONCLUSIONS: The Modified Tardieu
      Scale did not provide acceptable high inter-rater reliability in the measurement
      of muscle spasticity in patients with hemiplegia when used by raters of limited
      experience.

PMID- 19117180
TI  - Functional recovery following traumatic vs non-traumatic brain injury: a case
      controlled study.
AB  - PRIMARY OBJECTIVE: To explore differences in rate of recovery and functional
      outcome in case-matched patients with traumatic (TBI) vs non-traumatic brain
      injury (non-TBI) during inpatient rehabilitation and 1 year post-insult. RESEARCH
      DESIGN: Retrospective comparison study and case-controlled design. METHODS AND
      PROCEDURES: Demographic data, severity of injury, functional outcome measures and
      outcomes at 1 year follow-up were collected on 573 patients (404 TBI; 169 non
      TBI) admitted to a multidisciplinary neurorehabilitation programme. After general
      cohort comparisons, 86 TBI and 86 non-TBI patients were matched on age, severity
      of injury and functional outcome scores. MAIN OUTCOMES AND RESULTS: In the
      general cohort analyses, TBI patients demonstrated better outcomes at discharge
      as indicated by lower Disability Rating Scale (DRS) scores and higher gain and
      efficiency scores on both motor and cognitive sub-scales of the Functional
      Independence Measure (FIM). After matching patients, TBI patients showed greater
      functional improvement throughout their rehabilitation stay. Outcomes at 1 year
      follow-up were mixed; TBI patients showed better outcomes compared to non-TBI
      patients on DRS scores; however, FIM scores were not significantly different.
      CONCLUSIONS: Results from the present study support the hypothesis that TBI
      patients achieve greater functional improvements compared to non-TBI patients
      when matched according to injury and demographic characteristics.

PMID- 19117181
TI  - Effect of head-only sub-chronic and chronic exposure to 900-MHz GSM
      electromagnetic fields on spatial memory in rats.
AB  - PRIMARY OBJECTIVE: This study was carried out to investigate the behavioural
      effects of sub-chronic and chronic head-only exposure to 900 MHz GSM (Global
      System for Mobile communications) in male rats. METHODS: Rats were exposed for 45
      minutes per day, at a brain-averaged specific absorption rate (SAR) = 1.5 W Kg(
      1) or 15 minutes per day at a SAR = 6 W Kg(-1), during 8 or 24 weeks. Then, their
      spatial memory was tested using the radial-arm maze. In the first phase (10
      days), rats were trained to visit the eight arms of the maze without returning to
      an arm already visited. In the second phase (8 days), a 45-minute intra-trial
      delay was introduced after four visited arms. RESULTS: Performance of exposed
      rats (1.5 or 6 W Kg(-1)) was compared with that of sham, negative control and
      positive control rats. Scopolamine treatment in the positive control rats induced
      deficit in spatial memory task in the second phase of the test. However, spatial
      memory task was unaffected in exposed rats. CONCLUSION: Sub-chronic and chronic
      head-only exposure of rats to GSM 900 MHz signal (45-minutes, SAR = 1.5 or 15
      minutes, SAR = 6 W Kg(-1)) did not induce spatial memory deficit in the radial
      arm maze.

PMID- 19117182
TI  - Reliability of dynamometry to quantify isometric strength following traumatic
      brain injury.
AB  - OBJECTIVE: To investigate the within-session reliability and test-re-test
      reliability of hand-held dynamometry (HHD) to quantify strength in hip flexors,
      quadriceps, plantarflexors and triceps brachii following traumatic brain injury
      (TBI). DESIGN: Within-session reliability was examined across six consecutive
      trials of HHD. Test-re-test reliability was examined between two sessions
      separated by 7 days. SETTING: Private physical therapy practice, Melbourne,
      Australia. PARTICIPANTS: Ten adults with TBI with a mean age of 32.5 years (range
      = 19-63, SD = 12.8) and mean time after injury of 12.2 years (range = 2.3-26, SD
      = 8.6). MAIN OUTCOME MEASURES: Isometric strength measured by HHD. RESULTS: Test
      re-test reliability of HHD following TBI was good when repeated tests occurred
      within a single session. Within a session, the first trial was the most variable
      out of the six examined. Of the four muscles examined, re-test measures of
      strength for the quadriceps, plantarflexors and triceps were the most reliable.
      For the hip flexors an increase greater than 3.1 kg (28%) was needed before real
      change could be detected. Test-re-test reliability was higher for muscles tested
      on the more affected side (ICC((2,1)) = 0.55-0.93) than muscles tested on the
      less affected side (ICC((2,1)) = 0.09-0.86). CONCLUSIONS: To gain a
      representative measure of isometric strength using HHD in a single session, three
      trials are recommended. The first is for familiarization and trials 2 and 3 are
      averaged to provide a typical measure of isometric muscle strength. Further
      research needs to occur but alternative methods to quantify muscle strength might
      be needed if repeated measures are to be performed over a 7-day interval.

PMID- 19117185
TI  - Topical estrogen therapy in the management of postmenopausal vaginal atrophy: an
      up-to-date overview.
AB  - Vaginal atrophy, a manifestation of estrogen deprivation after the menopause,
      could affect up to 60% of women, with a significant impact on their quality of
      life. It is often under-diagnosed and inadequately treated. Symptoms are more
      common and severe in breast cancer survivors. Systemic estrogen replacement
      therapy may be unacceptable for many women because of the concerns over possible
      risks and may not cure vaginal symptoms in up to 45% of users. Non-medicated
      vaginal lubricants or moisturizers have been found to be no better than placebo
      and less effective than estrogen. Topical vaginal estrogen preparations reverse
      atrophic changes and relieve associated symptoms, while avoiding systemic
      effects. This article provides an up-to-date overview of the role, safety and
      effectiveness of topical vaginal estrogen therapy.

PMID- 19117186
TI  - Assessment of sexuality among middle-aged women using the Female Sexual Function
      Index.
AB  - OBJECTIVE: The purpose of the present investigation was to assess sexual function
      among middle-aged women and determine related risk factors (personal and partner)
      for sexual dysfunction. METHODS: In this cross-sectional study, women aged 40-59
      years were requested to fill out the Female Sexual Function Index (FSFI) and a
      general demographic questionnaire containing personal and partner data. RESULTS:
      A total of 409 women with a mean age of 47 +/- 5.3 years were surveyed. Of these,
      42.1% were premenopausal, 24.4% perimenopausal and 33.5% postmenopausal. At the
      time of survey, 10.5% of women were hysterectomized, 1.5% used psychotropic
      drugs, and 9.8% were on hormone therapy (HT) for the menopause; 28.1% had less
      than 12 years of schooling and 80.4% had only one partner at the moment of
      survey. Among their male partners, 7.3% abused alcohol, 10.3% had erectile
      dysfunction, 11.2% premature ejaculation and 63.83% were faithful partners. Mean
      (+/- standard deviation) scores for the FSFI domains were: desire (3.7 +/- 1.2),
      arousal (3.1 +/- 2.5), lubrication (3.3 +/- 2.6), orgasm (2.6 +/- 2.3),
      satisfaction (4 +/- 1.7), and pain/dyspareunia (3.2 +/- 2.6). The mean total FSFI
      score was 20.1 +/- 12.4 (median 24.7). In this series, the prevalence of female
      sexual dysfunction (FSFI score <or=26.55) was 55.7%, with women presenting
      difficulties across all domains of female sexual function but mostly in the
      dyspareunia and lubrication domains. Logistic regression analysis determined that
      female age (odds ratio (OR) 3.3, 95% confidence interval (CI) 1.6-6.8), p =
      0.001), postmenopausal status (OR 2.8, 95% CI 1.3-6.1, p = 0.007), partner's age
      (OR 2.0, 95% CI 1-4, p = 0.03), educational level (OR 2.7, 95% CI 1.5-5, p =
      0.001), and the presence of erectile dysfunction (OR 3.8, 95% CI 1.3-10.9, p =
      0.01) and premature ejaculation (OR 4.1, 95% CI 1.4-11.7, p = 0.0001)
      significantly increased the risk for female sexual dysfunction. Partner
      faithfulness (OR 0.2, 95% CI 0.1-0.4, p = 0.001) and menopausal HT use (OR 0.4,
      95% CI 0.1-1, p = 0.04) decreased this risk. CONCLUSIONS: In this series, male
      sexual health and demographic profile and female HT use were relevant
      determinants for sexual functioning among middle-aged women.

PMID- 19117187
TI  - Sexuality and amputation: a systematic literature review.
AB  - PURPOSE: To systematically examine the state of research on sexuality and
      amputees. METHODS: A total of five publication databases were searched: Pubmed,
      Cinahl, Embase, Psychinfo and Recall. RESULTS: A total of 11 eligible studies was
      found. The studies were characterised by a diversity of study populations,
      sampling methods, gender and age distributions, assessment methods, and outcomes
      measures. The use of the terminology regarding sexuality was ambiguous. All
      studies found an impact of the amputation of a limb on some part of sexual
      functioning (or concerns about) to some degree. CONCLUSIONS: Studies on sexuality
      and amputees are very diverse and terminology is ambiguous. Amputation of a limb
      has an impact on sexual functioning. Amputees complain that there is little
      support from professionals. The authors recommend the use of the ICF terminology.
      Suggestions for future research are given.

PMID- 19117188
TI  - Disability and rehabilitation: assistive technology. Introduction.

PMID- 19117189
TI  - A study of low-cost, robust assistive listening system (ALS) based on digital
      wireless technology.
AB  - PURPOSE: We have developed a simple, low-cost digital wireless broadcasting
      system prototype, intended for a classroom of hearing impaired students. The
      system is designed to be a low-cost alternative to an existing FM system. METHOD:
      The system implemented is for short-range communication, with a one-transmitter,
      multiple-receiver configuration, which is typical for these classrooms. The data
      is source-coded for voice-band quality, FSK modulated, and broadcasted via a 915
      MHz radio frequency. A DES encryption can optionally be added for better
      information security. RESULTS: Test results show that the system operating range
      is approximately ten metres, and the sound quality is close to telephone quality
      as intended. We also discuss performance issues such as sound, power and size, as
      well as transmission protocols. CONCLUSIONS: The test results are the proof of
      concept that the prototype is a viable alternative to an existing FM system.
      Improvements can be made to the system's sound quality via techniques such as
      channel coding, which is also discussed.

PMID- 19117190
TI  - An experience on wheelchair bank management.
AB  - In this article, we described the wheelchair bank program at a local hospital and
      our experiences in managing the service over the past 10 years from 1996 to 2005.
      This article also reported statistical information related to the acquisitions of
      wheelchairs and adaptive components, including body support and pressure relief
      systems. The cost benefit of recycling seating and mobility equipments for use by
      children with neuromuscular diseases was revealed. With the reference of the
      reported data, the demands on specific types of wheelchairs and adaptive parts
      were disclosed to facilitate budget planning of similar services.

PMID- 19117191
TI  - Axiomatic design theory for the analysis, comparison, and redesign of curriculum
      for special education.
AB  - This paper explores a novel approach to instructional planning using the
      axiomatic design theory to create an optimized curriculum. First, an existing
      piece of curriculum is analyzed by axiomatic design approach and design matrices
      are made to check whether the independence axiom is satisfied or not. Second,
      functional requirements (FRs) are derived from the FRs of the existing
      curriculums developed through conventional methods. Constraints (Cs) are defined
      considering the time and subject. Design parameters (DPs) are conceived in
      physical domain to satisfy these specified FRs and Cs, and two alternative DPs
      for one FR are proposed. One of these alternatives having the least information
      content is selected by defining FRs as the minimization of the irrelevant
      subjects/topics and time. Also feasibility is estimated by comparing the
      information content of the redesigned curriculum with that of other curriculums
      in consideration of costs-involved, time, and subjects-relevance.

PMID- 19117192
TI  - Collaborative path planning for a robotic wheelchair.
AB  - Generating a path to guide a wheelchair's motion faces two challenges. First, the
      path is located in the human environment and that is usually unstructured and
      dynamic. Thus, it is difficult to generate a reliable map and plan paths on it by
      artificial intelligence. Second, the wheelchair, whose task is to carry a human
      user, should move on a smooth and comfortable path adapted to the user's
      intentions. To meet these challenges, we propose that the human operator and the
      robot interact to create and gradually improve a guide path. This paper
      introduces design tools to enable an intuitive interaction, and reports
      experiments performed with healthy subjects in order to investigate this
      collaborative path learning strategy. We analyzed features of the optimal paths
      and user evaluation in representative conditions. This was complemented by a
      questionnaire filled out by the subjects after the experiments. The results
      demonstrate the effectiveness of this approach, and show the utility and
      complementarity of the tools to design ergonomic guide paths.

PMID- 19117193
TI  - Design and development of a novel balancer with variable difficulty for training
      and evaluation.
AB  - This paper presents a novel, portable and cost-effective balance trainer with the
      necessary important features to improve the reach of rehabilitation to the
      masses. There are three factors that contribute to a person's ability to maintain
      standing balance: Proprioceptive feedback (from the joints), vision, and the
      vestibular system. These systems can be affected by injury, infection, or brain
      damage caused by stroke. One example of such injuries is ankle injury. A large
      focus of the physiotherapy and sports medicine community is using postural
      control tasks to prevent, assess and rehabilitate patients. Unfortunately, there
      are presently two extreme ends of balance training devices. On one end, there is
      high-end equipment which only large hospitals are capable of buying. On the other
      end are the simple balance boards which offer limited features. To develop the
      new balance trainer - the Pro.Balance - therapists at the Singapore General
      Hospital drafted a new 'wish list' of requirements. The prototype was built at
      the Nanyang Technological University, Singapore, and was commercialized by Lab
      Rehab Pte Ltd as the Pro.Balance. The device has a small footprint, incorporating
      only the most important and frequently used functions. These functions include
      being able to provide different levels of difficulty, setting different
      difficulties in different directions, the storing of a patient's performance,
      real-time visual feedback to aid the patient and different types of modes for
      different purposes. Springs are used to vary the amount of supporting moments,
      thus varying the difficulty levels. This paper describes the design and features
      of the Pro.Balance.

PMID- 19117194
TI  - Dysarthric speech characteristics of Thai stroke patients.
AB  - The dysarthric speech characteristics of 14 Thai stroke patients were assessed by
      Computerized Articulation Test program 1. Each speaker had been tested for speech
      correctness of all Thai phonemes. As the results, the error patterns were
      analyzed. Vowels and tonal characteristics were the most intact characteristics,
      while speech reduction of the cluster consonants was the most impaired feature.
      Both initial and final consonants were frequently substituted, followed by
      omission and distortion. Generally, monophthong vowels, low and mid tone, and
      unaspirated consonants were produced more precisely than the other features.

PMID- 19117195
TI  - Establishment of resource portal of assistive technology in Taiwan.
AB  - PURPOSE: To establish an Assistive Technology (AT) resource portal for users,
      professionals and policy-makers in Taiwan to provide a new and versatile
      information network for AT popularization. METHOD: The Centre for AT Resources
      and Popularization (CATR@P), integrated the resources primarily from five AT
      Resource Centres of the Ministry of Interior in Taiwan. CATR@P invited
      representatives of organizations for people with disabilities, AT specialists and
      policy-makers to join the task force. A web company was responsible for website
      software design and collaboration with CATR@P, which included planning portal
      functions, all user-friendly interfaces and pilot testing. RESULTS: The Resource
      Portal of AT was officially online in October 2006. The portal was structured
      with 19 main functions and the contents of this new portal are versatile and
      multifunctional. It contains vast amounts of national and international resources
      such as archives of AT centres, AT products, a professionals directory, websites
      linkage, full text of the AT Companion Journal, E-paper, on-line consultation
      services, frequently asked questions, and on-line questionnaires. CONCLUSIONS:
      Integration of Taiwan AT resources in conjunction with the internet technology
      has made resources more available for people with disabilities and society.

PMID- 19117196
TI  - Experiment on a novel user input for computer interface utilizing tongue input
      for the severely disabled.
AB  - PURPOSE: This paper introduces a novel passive tongue control and tracking
      device. The device is intended to be used by the severely disabled or
      quadriplegic person. METHOD: The main focus of this device when compared to the
      other existing tongue tracking devices is that the sensor employed is passive
      which means it requires no powered electrical sensor to be inserted into the
      user's mouth and hence no trailing wires. This haptic interface device employs
      the use of inductive sensors to track the position of the user's tongue. RESULT:
      The device is able perform two main PC functions that of the keyboard and mouse
      function. The results show that this device allows the severely disabled person
      to have some control in his environment, such as to turn on and off or control
      daily electrical devices or appliances; or to be used as a viable PC Human
      Computer Interface (HCI) by tongue control. CONCLUSION: The operating principle
      and set-up of such a novel passive tongue HCI has been established with
      successful laboratory trials and experiments. Further clinical trials will be
      required to test out the device on disabled persons before it is ready for future
      commercial development.

PMID- 19117197
TI  - Touching force response of the piezoelectric Braille cell.
AB  - PURPOSE: The objective of this research is to investigate dynamic responses of
      the piezoelectric Braille cell when it is subjected to both electrical signal and
      touching force. METHOD: Physical behavior of the piezoelectric actuator inside
      the piezoelectric Braille cell is analyzed. The mathematical model of the
      piezoelectric Braille system is presented. Then, data of visually impaired people
      using a Braille Note is studied as design information and a reference input for
      calculation of the piezoelectric Braille response under the touching force.
      RESULTS: The results show dynamic responses of the piezoelectric Braille cell.
      The designed piezoelectric bimorph has a settling time of 0.15 second. The
      relationship between the Braille dot height and applied voltage is linear. The
      behavior of the piezoelectric Braille dot when it is touched during operation
      shows that the dot height is decreased as the force increases. CONCLUSIONS: The
      result provides understanding of the piezoelectric Braille cell behavior under
      both touching force and electrical excitation simultaneously. This is the
      important issue for the design and development of piezoelectric Braille cells in
      senses of controlling Braille dot displacement or force-feedback in the future.

PMID- 19117198
TI  - Proceedings of the inaugural International Convention for Rehabilitation
      Engineering & Assistive Technology (i-CREATe). April 23-26, 2007. Singapore.

PMID- 19117199
TI  - Deciphering a conformation-specific epitope of hCG-beta through Immunokinetics.
AB  - Proteins and peptides are comprised of both sequence-specific and conformation
      specific epitopes. Sequence-specific epitopes are delineated by a peptide
      approach and other robust methods like competition assays, gene expression
      assays, synthetic peptide library based assays, etc. Available methods for
      deciphering conformation-specific epitopes are cumbersome (X-ray crystallography,
      etc.), time-consuming, and require expensive equipment. Therefore, it is
      indispensable to develop a simple method for identification and mapping of
      conformation-specific epitopes. In the present investigation, the radiolabeled
      human chorionic gonadotropin-beta ((125)IhCGbeta) was employed as a probe and
      nitrocellulose (NC) as a solid support to immobilize monoclonal antibody (MAb)
      G(1)G(10).1. The NC-G(1)G(10).1-(125)IhCGbeta complex (NC(com)) was prepared and
      the dissociation of radiolabeled hCGbeta was carried out in the presence of
      excess unlabeled ligate. From the experimental dissociation data under varying
      ionic strength, dissociation constants (k(-1)), association constants (k(+1)),
      and affinity constants (k(a)) were calculated. The values obtained were utilized
      in exploring the amino acid residues constituting an epitopic region of hCGbeta
      involved in interaction with the complementary paratope on MAb G(1)G(10).1.
      Kinetic data of the present study supported our recently published findings
      [using single step-solid phase radioimmunoassay (SS-SPRIA)] that the core region
      of a conformation-specific epitope of hCGbeta consists of Arg (94, 95) and Asp
      (99) while a Lys (104) and a His (106) are in proximity to the core epitopic
      region. Therefore, the results of the present investigation suggested that the
      dissociation kinetics coupled with SS-SPRIA unequivocally assists in deciphering
      amino acid residues constituting a conformation-specific epitope of hCGbeta.

PMID- 19117200
TI  - A new artificial antigen of the hepatitis E virus.
AB  - An artificial antigen composed of 12 small antigenic regions derived from the
      ORF2 and ORF3 HEV proteins was designed. The gene encoding for this artificial
      antigen was assembled from synthetic oligonucleotides by a new method called
      Restriction Enzyme-Assisted Ligation (REAL). The diagnostic relevance of this
      second generation HEV mosaic protein (HEV MA-II) was demonstrated by testing this
      antigen against a panel of 142 well defined anti-HEV positive and anti-HEV
      negative serum samples. The data obtained in this study support the substantial
      diagnostic potential of this HEV mosaic antigen.

PMID- 19117201
TI  - Neutralizing and binding antibodies to interferon beta in patients with multiple
      sclerosis: a comparison of assay results from three italian centres.
AB  - Interferon (IFN) beta therapy for multiple sclerosis (MS) is associated with the
      development of binding antibodies (BAbs) and neutralizing antibodies (NAbs) in a
      percentage of patients. This study investigated the reproducibility of results of
      two different antibody detection techniques using serum from 100 patients with MS
      who were receiving IFN beta therapy. Fifty samples were analysed using a
      commercially available kit-based BAb assay and a further 50 different samples
      were analysed using a widely used NAb cytopathic effect assay, at three different
      laboratories. All three centres agreed on the BAb status of all serum samples.
      However, only 84% agreement was reached on serum NAb status, and there was
      significant inter-laboratory variation in NAb titre values. Further analysis of
      these data revealed a correlation between the mean NAb titre and the coefficient
      of variation of serum samples, indicating greater discordance with higher NAb
      titres. A significant interlaboratory variation in NAb titres does exist; thus,
      caution is required when comparing titres from different centres. It is clear
      that validated detection assays are needed to accurately quantify NAb titres.

PMID- 19117202
TI  - Serum IgG responses to food antigens in the italian population evaluated by
      highly sensitive and specific ELISA test.
AB  - Using an optimized and validated ELISA method, we performed a serum test for
      assaying the binding capacity of serum IgG to proteins extracted from approx. 160
      different foods to investigate the reactivity of specific IgG antibodies in the
      Italian population composed of 6,879 subjects (4,551 females and 2,328 males). 44
      antigens showed an IgG response greater than 10% and only 14 aliments had an
      elevated reactivity greater than 20%, in particular, milk, from cow and goat, and
      several milk derivatives, along with egg albumen and yeasts. The IgG response to
      the high reactive food antigens depending on the age of the 6880 subjects was
      also analyzed. We demonstrated a high IgG response in a very large subject group
      to milk and milk derivatives, and egg albumin antigens, and we conclude that the
      validated ELISA test may be applied for the serum/plasma IgG antibody level
      determination as a useful indicator of adverse reactions to food and food
      hypersensitivity.

PMID- 19117203
TI  - Antibody response to Helicobacter pylori excretory antigen and the cross reaction
      study.
AB  - Helicobacter pylori is recognized as a major case of gastritis and peptic ulcer
      and a key factor in the development of gastric cancer, gastric lymphoma, and non
      ulcerative dyspepsia in man. The detection of antibodies specific for strains of
      H. pylori has demonstrated the value of serology for providing evidence of
      infection. The present study was conducted to detect the antigenic proteins of
      excretory antigen of H. pylori with Western blotting and examine whether anti-H.
      pylori IgG and IgA antibodies from H. pylori positive patients cross-react with
      antigens from other common bacterial pathogens. By using SDS-PAGE, 20 different
      proteins were found in the excretory antigen. By Western blotting and absorption
      studies, there were indications that anti-H. pylori IgA antibodies directed
      against 54 kDa, 50 kDa and 27 kDa cross-reacted with antigens from other
      bacteria, and that H. pylori proteins of 99 kDa, 88 kDa and 81 kDa possibly
      shared similar epitope with antigens of other pathogens not tested in the
      absorption studies. The cross-reactivity occurred in this study was not
      significantly affect the performance of the in-house ELISA.

PMID- 19117204
TI  - Antibody response for L1, E6, E7 HPV 16, and HPV 18 antigens in Tunisian women
      with cervical cancer.
AB  - Results obtained in the present work indicated that the Luminex assay is more
      sensitive than ELISA. The reactivity to the early antigens E6 and E7 was 37%
      versus 42% for HPV 16 and 21% versus 20% for HPV 18 among cervical cancer cases
      using ELISA. However, these ratios were 44% and 61%, respectively, for E6 and E7
      HPV 16 versus 28% and 21% for E6 and E7 HPV 18 when using the Luminex technique.
      Data also indicated that HPV 16 and HPV 18 showed distinct profiles for the
      different antigens tested. Finally, the differences in antibody responses between
      cervical cancer cases and benign cases toward the different antigens were
      significant.

PMID- 19117206
TI  - Isolation and some characteristics of Lipoxygenase from aromatic brown rice
      (Oryza sativa L.) cv. Khao Dawk Mali 105.
AB  - Lipoxygenase from Khao Dawk Mali 105 aromatic brown rice was isolated by
      extracting brown rice liquid nitrogen powder using 0.2 M phosphate buffer pH 7,
      fractionating with 30-60% (NH(4))(2)SO(4), dialyzing and gel filtration on
      Sephadex G-200. The optimum pHs for dialyzed lipoxygenase activity were around
      7.5 and 9.5. The enzyme appeared to be completely inactivated after heating 30
      min at 70 degrees C, 20 min at 80 degrees C and 10 min at 90 degrees C. The
      enzyme could be inhibited by MgCl(2), ZnCl(2), KCl, BHA, vitamin E, vitamin C,
      and BHT; however, CaCl(2) acted as the enzyme activator.

PMID- 19117205
TI  - Determination of trace amount of cyanobacterial toxin in water by microchip based
      enzyme-linked immunosorbent assay.
AB  - Routine monitoring of microcystin in natural waters is difficult because the
      concentration of the toxin is usually lower than the detection limits. As a more
      sensitive detection method for microcystin, we developed a microchip based enzyme
      linked immunosorbent assay (ELISA) based on monoclonal antibodies. New monoclonal
      antibodies against the microcystin leucine-arginine variant (MCLR), a cyclic
      peptide toxin of the freshwater cyanobacterium Microcystis aeruginosa, were
      prepared from cloned hybridoma cell lines. We used keyhole limpet hemocyanin(KLH)
      conjugated MCLR as an immunogen for the production of mouse monoclonal antibody.
      The immunization, cell fusion, and screening of hybridoma cells producing anti
      MCLR antibody were conducted. Since the ELISA test was highly sensitive, the
      newly developed microchip based ELISA can be suitable for the trace analysis of
      cyanobacterial hepatotoxins, microcystins in water. The linear responses of
      monoclonal antibodies with different concentrations of microcystin LR were
      established between 0.025 and 0.3 ng/mL.

PMID- 19117207
TI  - Database for physiologically based pharmacokinetic (PBPK) modeling: physiological
      data for healthy and health-impaired elderly.
AB  - Physiologically based pharmacokinetic (PBPK) models have increasingly been
      employed in chemical health risk assessments. By incorporating individual
      variability conferred by genetic polymorphisms, health conditions, and
      physiological changes during development and aging, PBPK models are ideal for
      predicting chemical disposition in various subpopulations of interest. In order
      to improve the parameterization of PBPK models for healthy and health-impaired
      elderly (herein defined as those aged 65 yr and older), physiological parameter
      values were obtained from the peer-reviewed literature, evaluated, and entered
      into a Microsoft ACCESS database. Database records include values for key age
      specific model inputs such as ventilation rates, organ volumes and blood flows,
      glomerular filtration rates, and other clearance-related processes. In total, 528
      publications were screened for relevant data, resulting in the inclusion of 155
      publications comprising 1051 data records for healthy elderly adults and 115 data
      records for elderly with conditions such as diabetes, chronic obstructive
      pulmonary disease (COPD), obesity, heart disease, and renal disease. There are no
      consistent trends across parameters or their associated variance with age; the
      gross variance in body weight decreased with advancing age, whereas there was no
      change in variance for brain weight. The database contains some information to
      inform ethnic and gender differences in parameters; however, the majority of the
      published data pertain to Asian (mostly Japanese) and Caucasian males. As
      expected, the number of records tends to decrease with advancing age. In addition
      to a general lack of data for parameters in the elderly with various health
      conditions, there is also a dearth of information on blood and tissue composition
      in all elderly groups. Importantly, there are relatively few records for alveolar
      ventilation rate; therefore, the relationship between this parameter and cardiac
      output (usually assumed to be 1:1) in the elderly is not well informed by the
      database. Despite these limitations, the database represents a potentially useful
      resource for parameterizing PBPK models for the elderly to facilitate the
      prediction of dose metrics in older populations for application in risk
      assessment.

PMID- 19117208
TI  - Osprey: worldwide sentinel species for assessing and monitoring environmental
      contamination in rivers, lakes, reservoirs, and estuaries.
AB  - In the United States, many fish and wildlife species have been used nationwide to
      monitor environmental contaminant exposure and effects, including carcasses of
      the bald eagle (Haliaeetus leucocephalus), the only top avian predator regularly
      used in the past. Unfortunately, bald eagles are sensitive to investigator
      intrusion at the nest. Thus, the osprey (Pandion haliaetus) is evaluated as a
      potential sentinel species for aquatic ecosystems. Several characteristics
      support the choice of the osprey as a sentinel species, including: (1) fish
      eating diet atop the aquatic food web, (2) long-lived with strong nest fidelity,
      (3) adapts to human landscapes (potentially the most contaminated), (4) tolerates
      short-term nest disturbance, (5) nests spatially distributed at regular
      intervals, (6) highly visible nests easily located for study, (7) ability to
      accumulate most, if not all, lipophilic contaminants, (8) known sensitivity to
      many contaminants, and (9) nearly a worldwide distribution. These osprey traits
      have been instrumental in successfully using the species to understand population
      distribution, abundance, and changes over time; the effects of various
      contaminants on reproductive success; how contaminants in prey (fish on biomass
      basis) contribute to egg concentrations (i.e., biomagnification factors); and
      spatial residue patterns. Data summarized include nesting population surveys,
      detailed nesting studies, and chemical analyses of osprey egg, organ, blood, and
      feather samples for contaminants that bioaccumulate and/or biomagnify in aquatic
      food webs; and biochemical evaluations of blood and various organs. Studies in
      the United States, Canada, Mexico, Europe, and elsewhere have shown the osprey to
      be a useful sentinel species for monitoring selected environmental contaminants,
      including some emerging contaminants in lakes, reservoirs, rivers, and estuaries.

PMID- 19117209
TI  - Cigarette smoke, inflammation, and lung injury: a mechanistic perspective.
AB  - Inflammation is a common feature in the pathogenesis of cigarette smoke
      associated diseases. The recruitment of inflammatory cells into the lung
      following cigarette smoke exposure presents a risk of tissue damage through the
      release of toxic mediators, including proteolytic enzymes and reactive oxygen
      species. This review represents a toxicological approach to investigation of
      cigarette smoke-induced lung injury, with a focus on laboratory studies and an
      emphasis on inflammatory mechanisms. The studies discussed in this review analyze
      the role of inflammation and inflammatory mediators in the development of injury.
      In cases where information relating to cigarette smoke is limited, examples are
      taken from other models of lung injury applicable to cigarette smoke. The primary
      aim of the review is to summarize published work so as to permit (1) an
      evaluation of chronic lung injury and inflammatory responses in animal models,
      (2) a discussion of inflammatory mediators in the development of chronic injury,
      and (3) identification of immunological mechanisms of injury. These studies
      discuss the currently understood roles of cytokines, cell adhesion molecules, and
      oxidative stress in inflammatory reactions and lung injury. A role for lipocortin
      1 (annexin 1), a naturally occurring defense factor against inflammation, is
      discussed because of the possibility that impaired synthesis and degradation of
      lipocortin 1 will influence immune responses in animals exposed to cigarette
      smoke either by augmenting T helper cell Th1 response or by shifting Th1 to Th2
      response. While Th1 augmentation will increase the risk for development of
      emphysema, Th1 to Th2 shift will favor development of asthma.

PMID- 19117210
TI  - Microcystin dynamics in aquatic organisms.
AB  - Eutrophication of surface water has increased significantly during the past
      decade, resulting in increased occurrences of toxic blooms. Cyanotoxins have
      become a global health threat to humans, wild animals, or domestic livestock.
      Hepatotoxic microcystins (MC) are the predominant cyanotoxins, which accumulate
      in aquatic organisms and are transferred to higher trophic levels. This is an
      issue of major concern in aquatic toxicology, as it involves the risk for human
      exposure through the consumption of contaminated fish and other aquatic
      organisms. The persistence and detoxification of MC in aquatic organisms are
      important issues for public health and fishery economics. Bioaccumulation of MC
      depends on the toxicity of the strains, mode of feeding, and detoxication
      mechanisms. Although mussels, as sessile filter feeders, seem to be organisms
      that ingest more MC, other molluscs like gastropods, as well as zooplankton and
      fish, may also retain average similar levels of toxins. Edible animals such as
      some species of molluscs, crustaceans, and fish present different risk because
      toxins accumulate in muscle at low levels. Carnivorous fish seem to accumulate
      high MC concentrations compared to phytophagous or omnivorous fish. This review
      summarizes the existing data on the distribution and dynamics of MC in
      contaminated aquatic organisms.

PMID- 19117211
TI  - Bioassays for the evaluation of landfill leachate toxicity.
AB  - This article reviews the application of bioassays for assessing the toxicity
      hazard posed by landfill leachate discharged to an aquatic environment. Landfill
      leachate is a complex mixture of chemicals; thus it is difficult to assess the
      risk posed to aquatic wildlife using standard chemical identification techniques,
      such as gas chromatography-mass spectroscopy (GC-MS). From this review it is
      clear that toxicity testing, using species that represent the different trophic
      levels, is a superior way to predict the risk posed by discharge than chemical
      analysis. Previous studies assessed leachate toxicity using bacteria, algae,
      plants, invertebrates, fish, and genotoxicity. Studies showed that leachate
      exhibits a wide range of toxicities to the species tested. Ammonia, alkalinity,
      heavy metals, and recalcitrant organics were identified to be the cause of
      adverse responses from the test organisms. Concentrations of these chemicals were
      found to depend upon the types of waste landfilled. As part of this review,
      Slooff analysis was applied to published results to calculate the sensitivity of
      test species. It was concluded that Lemna minor and Thamnocephalus platyurus were
      the most sensitive tests and, Vibrio fischeri (Microtox) was the least sensitive
      test available. Little is known about the sensitivity of each species to the
      different types of waste that might have been landfilled. A battery of tests
      needed for a more accurate assessment of landfill leachate is proposed. Some of
      the more common tests have been replaced by more sensitive tests that produce
      more relevant results for the industry and regulators.

PMID- 19117212
TI  - Autologous graft-versus-host disease after denileukin diftitox and autologous
      stem cell transplantation for refractory T-cell lymphoma.

PMID- 19117213
TI  - Management of the advanced phases of chronic myelogenous leukemia in the era of
      tyrosine kinase inhibitors.
AB  - Imatinib has revolutionised the management of chronic phase chronic myelogenous
      leukemia (CML). Unfortunately it has had less of an impact on the management of
      the advanced phases of CML. These historically difficult-to-treat phases of
      disease remain largely resistant to therapy. Even when responses are obtained
      with the tyrosine kinase inhibitors, they are brief, particularly in blast phase
      (BP) disease. Allogeneic stem cell transplantation is the only curative option
      for these patients and should be considered early as an integral part of the
      treatment plan. But transplant outcomes are dependent on cytogenetic and gross
      disease burden at the time of transplant. This review will compare and contrast
      the various tyrosine kinase- and non-tyrosine kinase inhibitor-based treatments
      for accelerated and BP CML before allogeneic transplantation.

PMID- 19117214
TI  - Student selected components: do students learn what teachers think they teach?
AB  - BACKGROUND: It is well recognized that what teachers teach and what students
      learn may not be the same. This applies to all parts of the undergraduate medical
      curriculum, but may be especially relevant to student selected components, which
      vary substantially in their educational content. This has not been studied
      previously. AIMS: To compare perceptions of students and supervisors in relation
      to learning outcomes addressed by student selected components, and thus to
      examine differences between what is taught and what is learned. METHODS:
      Supervisors (n = 69) were asked to indicate which of twelve learning outcomes
      they felt were components of teaching and assessment. Upon completion of each
      SSC, students were required to complete the same outcomes template as part of
      their feedback (n = 644). Perceptions were compared in two ways: (1) a colour
      coded 'traffic-light' system was used to record agreement/disagreement between
      students and supervisors of individual SSCs; (2) differences in perception of
      outcomes across the entire SSC programme were compared using the chi(2)
      statistic. RESULTS: (1) The 'traffic-light' system readily identified individual
      SSCs where significant disagreement existed and which were subject to further
      scrutiny. (2) More students than supervisors thought that outcome 2 (competent to
      perform practical procedures) was a component of teaching and assessment (41.8% v
      27.5%, chi(2) = 5.24, p = 0.02), whereas more supervisors than students thought
      that outcome 6 (competent in communication skills) (97.1% v 82.1%, chi(2) = 6.91,
      p = 0.009) and outcome 7 (competent to retrieve and handle information) (100% v
      93.7%, chi(2) = 4.8, p = 0.02) were. CONCLUSIONS: Significant disagreement exists
      about the outcomes addressed by SSCs, suggesting that students do not always
      learn what teachers think they teach. The use of two complementary approaches
      allows global and individual comparisons to be drawn and thus provides a powerful
      tool to address this important issue.

PMID- 19117215
TI  - Public health education in Ege University Medical Faculty: developing a community
      oriented model.
AB  - BACKGROUND: Ege University Medical Faculty (EUMF) introduced a community-oriented
      curriculum in 2001. AIMS: To evaluate the new public health education program in
      EUMF curriculum. METHOD: The study adopted triangulated methods. Quantitatively,
      a comparison of the students who were exposed to a community-oriented curriculum
      (Year 4 in 2007) was made with the students who were exposed to the traditional
      curriculum (Year 4 in 2005) in terms of their assessment of their achievement of
      our learning objectives. A total of 255 students in 2005 (80.7%) and 243 students
      in 2007 (81.5%) were surveyed using a questionnaire. Qualitatively, five focus
      group- and five individual interviews were performed with the 2007 cohort.
      RESULTS: Except the one related to teamwork (p > 0.05) all learning objectives
      yielded significantly higher scores in the 2007 cohort than in the 2005 cohort (p
      < 0.05). The qualitative analysis supported the achievement of objectives in the
      2007 cohort. The students appreciated the relevance of public health education
      with clinical subjects and interactive methods, but criticized didactic lectures
      and written assignments. CONCLUSIONS: A community-oriented approach is more
      effective in achieving a holistic approach to health problems. Improving
      community-based activities and assessment methods would be more successful in
      integrating population health into medical training.

PMID- 19117216
TI  - Implementation of a competency-based residency curriculum: experiences from a
      resource-limited environment in the Caribbean.
AB  - BACKGROUND: The introduction of competency-based curricula in institutions
      situated in resource-limited environments is likely to pose new challenges for
      the implementation process. The St. Elisabeth Hospital (SEHOS) in Curacao, Dutch
      Caribbean, is affiliated to university teaching hospitals in the Netherlands. It
      is a teaching hospital in a resource-limited environment. AIMS: Following the
      revision of the curriculum of the Dutch paediatric residency training, the
      country's paediatric society mandated its implementation in all training
      institutions within Dutch sovereignty. We set out to implement the revised
      curriculum in SEHOS and highlight the benefits it may have in a setting like
      Curacao. METHOD: The intended learning outcomes for the 16-week project were (1)
      the implementation of the core changes in the curriculum and (2) conduct an
      assessment of the learning environment. The strategies used included informative
      meetings, workshop and lecture-based trainings, questionnaire surveys, and focus
      group interviews. RESULTS: Registrars and staff were successfully trained in how
      to use brief clinical assessments and digital portfolios. 'Departmental
      portfolio' was introduced as an innovative method of evaluating and monitoring
      departmental educational activities. CONCLUSIONS: Competency-based curricula can
      be successfully implemented in resource-limited environments. Educational experts
      in the local setting are crucial for the success of the process.

PMID- 19117217
TI  - Strengthening public health medicine training for medical students: development
      and evaluation of a lifestyle curriculum.
AB  - BACKGROUND: Lifestyle factors are major determinants for health and safety.
      Although many graduates lack interviewing and observational skills for prevention
      and student lifestyle often deteriorates during training, few medical schools
      teach comprehensive assessment of lifestyle, particularly in the context of the
      home environment. AIMS: A lifestyle curriculum was developed to teach basic
      causality and provide practical experience in assessing nutrition, exercise,
      safety, tobacco addiction, and food hygiene, together with generic skills in
      history taking, on-site observation, researching and presenting. METHODS:
      Lifestyle has been integrated into the first-year curriculum, evaluated, and
      improved at the United Arab Emirates University since 2001. After an introduction
      to determinants of health, students conduct a home interview and observational
      survey for family residential and traffic safety, smoking, and food hygiene. For
      nutrition and exercise, students assess personal lifestyle. Generic skills are
      developed in the context of lifestyle. Evaluations were by faculty and students,
      including assessed impact on knowledge, skills, and personal lifestyle. The
      lifestyle curriculum was compared with other countries by detailed search.
      RESULTS: Detailed evaluation found strong agreement/agreement among students that
      knowledge had improved on: counselling of patients and families 97%, promoting
      healthy lifestyles 100%; interviewing 88%; history taking 84%; using research for
      medical practice 89%; and importance of prevention 96%. Eighty six percent were
      stimulated to think in new ways about health. Improved personal diet was reported
      by 60% (p < 0.0004) and exercise by 55% (p < 0.0004), while 36% of non-users
      started wearing a safety belt in front (p < 0.0004) and 20% in the rear (p =
      0.008). Literature review found comprehensive lifestyle curricula to be rare.
      CONCLUSIONS: A lifestyle curriculum developed prevention-oriented history-taking
      and observation skills for health maintenance, addressing health priorities,
      improving medical student lifestyle, and strengthening generic skills. Since
      lifestyle is a major determinant of health, medical schools should consider
      development of an appropriate curriculum to address their local and national
      health priorities.

PMID- 19117218
TI  - Attitudes to e-learning, learning style and achievement in learning neuroanatomy
      by medical students.
AB  - BACKGROUND: Two main learning approaches adopted by students have been identified
      by research: deep (seeking for meaning motivated by interest in the subject
      matter) and surface (rote-learning motivated by fear of failure). There is
      evidence that learning approach is influenced by learning environment (e.g.
      Trigwell et al. 1999). Online courses pose the challenge of designing software
      that will encourage the more desirable approach to learning. AIMS: The aims were
      to evaluate how successful an online course is at encouraging deep approach to
      learning, which factors might influence the approach adopted towards it, and
      whether the approach adopted is related to academic performance. METHOD: Using
      205 second-year pre-clinical medical students, we compared their approach to
      learning, as measured by Biggs et al. (2001) 2F-SPQ-R, for a computer-aided
      learning (CAL) course in Neuroanatomy with that for their studies in general. We
      then examined student attitudes towards the CAL course and the ratings of the
      course Web pages in terms of the learning approach they encourage (done by 18
      independent raters). RESULTS: The students reported using significantly less deep
      approach to learning for the CAL course. However, their approach for the course
      was not related to results on a neuroanatomy assessment based on it. Enjoyment of
      the course, assessment of the amount of information in it as appropriate, and
      ease of understanding the course were all associated with a deeper approach. The
      only agreement between the raters of the CAL course was for some pages that
      included patient case studies, which were unanimously given a very high deep
      rating. Assessment marks for questions referring to these pages were higher than
      for the rest of the assessment. CONCLUSIONS: The study suggests that maximizing
      the use of clinical relevance should increase the interest and enjoyableness of
      the course and thereby aid deep learning and retention of information.

PMID- 19117219
TI  - Critical care recognition, management and communication skills during an
      emergency medicine clerkship.
AB  - BACKGROUND: Medical students need to learn how to recognize and manage critically
      ill patients; to communicate in critical situations with patients, families, and
      the healthcare team; and finally, to integrate technical knowledge with
      communication skills in caring for these patients. Meeting their needs will help
      prepare them to demonstrate, as physicians, the ability to synthesize information
      while simultaneously caring for patients, that the American Medical Association
      recently characterized as vital. AIMS: Responding to these needs, we developed
      and implemented a curriculum to enable students in a required emergency medicine
      clerkship to recognize, manage, and simultaneously communicate with critically
      ill patients. METHODS: The curriculum consisted of lectures and exercises on
      caring for the critically ill including: an introduction to the systematic
      approach; an interactive lecture on comprehensive communication; observation and
      discussion of real patients in the emergency department; participation in a
      single standardized patient encounter while peers and a faculty member observed
      them; assessment of students' own videotaped performance of the examination by
      using critical care and communication/interpersonal skills checklists; and
      receipt of private feedback based on the checklists from the faculty and the
      standardized patient. Students evaluated the curriculum at the end of the
      clerkship. RESULTS: Complete performance data for 46 students and curriculum
      evaluation data from 42 students were available. According to faculty assessment,
      students as a group performed 79.6% (SD 0.15) of the critical care and 70.9% (SD
      11.5%) of the communication skills. Students most often demonstrated Basic
      Interpersonal Skills (97.9%, SD 0.056) and least often demonstrated Empathy
      skills (41.7%, SD 0.235). Students rated the curriculum positively. CONCLUSIONS:
      It is feasible to integrate the teaching of communication skills with the
      recognition and management of critically ill patients. The next step will be to
      revise the curriculum to address student deficiencies and to evaluate its
      effectiveness more rigorously.

PMID- 19117220
TI  - Death by PowerPoint - the need for a 'fidget index'.
AB  - PowerPoint is an application designed to help the speaker or lecturer assemble
      professional looking slides to be used in oral presentations. The result sadly is
      often an unending stream of slides with bullet lists, animations that obscure
      rather than clarify the point and cartoons that distract from rather than convey
      the message. This paper examines what the speaker can do to avoid 'death by
      PowerPoint'. The options of an alternative communication format or an alternative
      presentation tool are considered. For most speakers, however, the problem is not
      with PowerPoint but with how they make use of it. Three approaches to making
      presentations using PowerPoint are described which should yield rich rewards and
      a more attentive and appreciative audience.

PMID- 19117221
TI  - Setting and maintaining standards in multiple choice examinations: AMEE Guide No.
      37.
AB  - The process of setting a standard when pass/fail decisions have to be made
      inevitably involves judgment about the point on the test score scale where
      performance is deemed to be adequate for the purpose for which the examination is
      set. As with any process which involves human judgment, setting this standard is
      likely to include a certain degree of error, which may result in some false
      positive and false negative decisions. The customary practice of maintaining a
      constant point on the test score scale at which pass/fail separations are made
      cannot be justified, as examinations vary in difficulty. The aim of standard
      setting procedures is to minimize such errors while accounting for the varying
      difficulty of examinations. A standard may be norm-referenced, where it is
      dependent on the performance of the particular group of examinees, or criterion
      referenced, where it is based on predetermined criteria, irrespective of examinee
      performance. Where certification of competence is the primary purpose of an
      examination, the latter is preferred as the decision to be made is whether an
      individual is competent to practise rather than competent compared to peers.
      Several methods of standard setting have been used, some of which are based
      solely on predetermined criteria, while others compromise between norm- and
      criterion-referenced standards. This guide examines the more commonly used
      methods of standard setting, illustrates the procedure used in each with the help
      of an example, and discusses the advantages and disadvantages associated with the
      use of each. The common errors made by judges in the standard setting process are
      pointed out and the manner in which judges should be selected, trained and
      instructed emphasized. A method used for equating similar tests set at different
      times with the intention of maintaining standards from one examination to the
      next is illustrated with an example. Finally, the guide proposes a practical
      method for arriving at a pre-determined standard by the proportionate selection
      of test-items of known relative difficulties in relation to minimally competent
      examinees.

PMID- 19117222
TI  - Medical education in Japan: a challenge to the healthcare system.
AB  - In response to a change in health and societal need, the system of medical
      education in Japan has undergone major reform within the last two decades.
      Although the general health status of Japanese citizens ranks amongst the highest
      in the world, a rapidly increasingly elderly population, a social insurance
      system in crisis and a decrease in the number of practicing physicians is
      severely affecting this enviable position. To compensate, the Government has
      reversed its previous decision to reduce the number of doctors. Concomitantly,
      public opinion is changing to that of support and sympathy for the practicing
      physician. In order to produce a new breed of future doctors, Japanese medical
      education has undergone major reform: problem-based learning and clinical skills
      development has been instituted in most medical schools, more rigid assessment
      methods, ensuring competency and fitness to practice have been introduced, and
      there has been an increase in purposeful clinical attachments with a hands-on
      approach rather than a traditional observation model. A new postgraduate
      residency programme, introduced in 2004, hopes to improve general competency
      levels, while medical schools throughout the country are paying attention to
      modern medical education and faculty development.

PMID- 19117225
TI  - Do you know?

PMID- 19117223
TI  - Formative evaluation of a pediatric digital library's educational content and
      comparison to national curricular standards.
AB  - BACKGROUND: U.S. medical education has undergone numerous regulatory changes; to
      maintain educational consistency and quality, these changes must be met with
      innovative educational methods. AIM: A formative evaluation of a pediatric
      digital library (PDL) documenting its content and comparing it to 3 national
      medical education curricula was performed. METHODS: The PDL's weekly cases are
      written using templates based on specific educational constructs. Cases (N = 150)
      were evaluated in November 2007. Data was tabulated by age group, specialty,
      symptom/presentation and disease/problem. Curriculum maps were developed from 3
      national curricula and topics were mapped to one or more equivalent PDL topics.
      Data was tabulated for total national curriculum topics, mapped PDL topics and
      weekly cases. RESULTS: The cases covered 100% of all pediatric age groups (N = 9)
      and specialties (N = 42). They covered 85% of the symptoms/problems (N = 127) and
      37.2% of the diseases/problems (N = 707). Although the PDL was not explicitly
      designed to meet these national curricula standards, >80% of the topics in these
      curricula were covered. CONCLUSIONS: The PDL broadly covered national curricular
      standards and represents an unstructured pediatric curriculum. It offers a
      complementary and alternative educational method of medical education for
      educators and learners at all stages of professional development.

PMID- 19117227
TI  - eMedical Teacher.

PMID- 19117229
TI  - Thirty-degree optical system for laparoscopic training.
AB  - The training systems used by starting laparoscopic surgeons for visual and motor
      adaptation employ zero-degree optics. However, as new laparoscopic surgery
      techniques make such optics obsolete, there is a need to design training and
      adaptation tools with other optics.

PMID- 19117230
TI  - Further arguments in support of a social humanistic perspective in physiotherapy
      versus the biomedical model.

PMID- 19117231
TI  - Philosophy of science and physiotherapy: an insight into practice.
AB  - This article presents an overview of the philosophy of science and applies such
      philosophical theory to clinical practice within physiotherapy. A brief history
      of science is followed by the theories of the four most commonly acknowledged
      philosophers, introduced in the context of examples from clinical practice. By
      providing direct links to practical examples, it demonstrates the possibilities
      of relating the logical basis of this field of study to the clinical setting. The
      relevance to physiotherapy is that, by relating this theory, clinicians can
      better understand and analyse the fundamental logic behind their practice. The
      insight this provides can benefit professional development in several ways. For
      the clinician, it permits more comprehensive and coherent reasoning and helps to
      relate evidence with respect to individual patients. On a larger scale, it
      encourages reflective discussion between peers around the virtues of alternative
      treatment approaches. Thus, this topic has the potential to guide clinical
      practice toward being more scientific and may help raise the credibility of the
      profession as a whole.

PMID- 19117232
TI  - An ethnographic study of physiotherapists' perceptions of their interactions with
      patients on a chronic pain unit.
AB  - Changes in health care brought about by the increased incidence of chronic
      conditions have resulted in an increased focus on patient self-directed care.
      This ethnographic study explores from the therapists' perspectives how
      therapist/patient interactions influence success or contribute to meeting the
      patients' goals on a pain management program. A team of physiotherapists were
      observed individually with their patients over a period of 6 months. Their
      interactions were audiotaped, transcribed, analysed, and cross-referenced to the
      field notes and the follow-up interviews with the therapists after each
      observation. The analysis was iterative, guided by questions and contextualised.
      Codes, categories, and evolving patterns of behaviour were documented, and three
      major themes were identified. The therapist/patient interactions demonstrated
      certain consistent standpoints toward the purpose of the program. The team judged
      those who achieved positive outcomes, as having entered into interactions
      typified by assertiveness, negotiation, and critical reflection. However, even
      the most able team of therapists will not be able to create a collaborative
      framework unless their patients are willing to grasp the opportunity offered to
      them, and they judged their least successful patients as having adopted unwilling
      and unrealistic interactions. Interactions of resistance or an inability to carry
      over problem solving skills into their lives resulted in a negative outcome for
      the patients and a stunting of the team's potential.

PMID- 19117233
TI  - After-hour physiotherapy services in a tertiary general hospital.
AB  - The aims of the present study were to describe the after-hour physiotherapy
      services in a tertiary general hospital, the patients and their demographics, and
      to determine which independent variables would predict physiotherapists'
      referrals to after-hour physiotherapy. A retrospective record review from April
      1, 2004, to April 30, 2005, identified 992 patients (mean age 63.8 years; 95%
      confidence interval [CI] 62.6-65.0 years) who were either referred by daytime
      physiotherapists (68%) or referred by medical practitioners for urgent attendance
      after hours (32%). Pneumonia was formally diagnosed medically in 20% (n=197) of
      the patients. Of all the patients who had surgery, upper abdominal or thoracic
      incisions formed the majority (61%; n=236). Whether patients had upper
      abdominal/thoracic surgery (estimated odds ratio 3.4; 95% CI 2.3-4.9) and the
      presence of pneumonia (2.8; 95% CI 1.9-4.2) were two independent factors
      identified from a logistic regression model predicting daytime physiotherapists'
      referral of patients to after-hour service. This model correctly predicted 65.5%
      of the cases. Most patients were seen for mucociliary clearance. Referral
      behaviour by physiotherapists reflects the basis of their clinical decision
      making and has implications for practice, training, and further research.

PMID- 19117234
TI  - Comparison of cervical vertebral separation in the supine and seated positions
      using home traction units.
AB  - This study was performed for the purpose of comparing the magnitude of cervical
      vertebral separation during cervical traction in supine and seated positions
      using home traction units. A repeated measures design with two within-subject
      factors (type of traction and time) was used. Seventeen asymptomatic volunteers
      received cervical traction in seated and supine position. Subjects received 5
      minutes of static traction in sitting or supine using a force of 13.6 kg while in
      15 degrees of neck flexion. A lateral radiograph of the cervical spine was taken
      before traction force was applied and after five minutes of static traction.
      Anterior and posterior distances between the inferior border of C2 and the
      superior border of C7 were measured by a radiologist. After supine traction there
      were significant increases (p=0.001) in posterior cervical vertebral separation
      compared to any changes after seated traction. There were no significant changes
      in anterior vertebral separation during either supine or seated traction
      positions (p=0.769). Supine cervical traction may be more effective for
      increasing posterior vertebral separation than seated cervical traction.

PMID- 19117235
TI  - Documentation of daily sit-to-stands performed by community-dwelling adults.
AB  - No information exists about how many sit-to-stands (STSs) are performed daily by
      community-dwelling adults. We, therefore, examined the feasibility of using a
      tally counter to document daily STSs, documented the number of daily STSs
      performed, and determined if the number of STSs was influenced by demographic or
      health variables. Ninety-eight community-dwelling adults (19-84 years) agreed to
      participate. After providing demographic and health information, subjects used a
      tally counter to document the number of STSs performed daily for 7 consecutive
      days. All but two subjects judged their counter-documented STS number to be
      accurate. Excluding data from these and two other subjects, the mean number of
      STSs for subjects was 42.8 to 49.3, depending on the day. The number was
      significantly higher on weekdays than weekends. No demographic or health variable
      was significantly related to the number of STSs in univariate or multivariate
      analysis. In conclusion, this study suggests that a tally counter may be a
      practical aid to documenting STS activity. The STS repetitions recorded by the
      counter in this study provide an estimate of the number of STSs that community
      dwelling adults perform daily.

PMID- 19117237
TI  - A model for left ventricular hypertrophy enabling non-invasive assessment of
      cardiac function.
AB  - OBJECTIVE: To develop a porcine model for Left Ventricular Hypertrophy (LVH) in
      which cardiac performance could be quantified non-invasively by Doppler
      ultrasound. DESIGN: Sixteen 5 kg piglets were divided into two groups. In the
      first group (n=12) we performed an aortic banding and in the second group (n=4) a
      sham-operation. Endpoints were echo-assessed left ventricular midseptal and free
      wall thickness, heart/body-weight ratio and cardiac myocyte diameter. RESULTS:
      Free-wall thickness: 0.77+/-0.013 cm in the intervention group and 0.60+/-0.006
      cm in the control group (p=0.015). Midseptal thickness: 0.79+/-0.015 cm in the
      intervention group and 0.58+/-0.010 cm in the control group (p=0.012). Heart/body
      weight ratio: 7.73+/-0.970 in the intervention group and 6.23+/-0.430 in the
      control group (p=0.003). Cardiac myocyte diameter: 19.6+/-4.9 microm in the
      intervention group and 11.0+/-1.9 microm in the control group (p=0.000).
      CONCLUSION: A chronic porcine model for LVH has been established in which Doppler
      ultrasound can be used to quantify cardiac function non-invasively.

PMID- 19117238
TI  - Better results with the new generation bare metal stents.

PMID- 19117239
TI  - Prognostic impact of hs-CRP and IL-6 in patients undergoing radiofrequency
      catheter ablation for atrial fibrillation.
AB  - AIM: The aim of this study was to assess the predictive value of inflammatory
      markers in patients with paroxysmal/persistent atrial fibrillation (AF) treated
      with radiofrequency (RF) catheter ablation. METHODS: Forty-six consecutive
      patients, mean age 55 years (range 31 - 81 yrs), with paroxysmal or persistent AF
      were treated with either segmental or circumferential pulmonary vein isolation
      ablation technique. All patients presented with sinus rhythm on inclusion. Holter
      monitoring lasting at least 14 days was performed before ablation and after 3
      months. Recurrent symptomatic AF or atrial tachycardia >10 minutes was considered
      failure and patients were offered a second ablation session. Interleukin-6 and
      high-sensitivity C-reactive protein were measured prior to ablation and at follow
      up visits. RESULTS: After a maximum of two ablations, 19 patients (41%) had SR
      without recurrence of AF after 12 months. Patients in SR had significantly lower
      left atrium diameter (p = 0.007) and lower values of both IL-6 (p = 0.007) and hs
      CRP (p = 0.018) at baseline before ablation. IL-6 concentration prior to ablation
      was an independent predictor of recurrent AF (p = 0.027). CONCLUSION: In patients
      with a history of paroxysmal or persistent AF treated with RF catheter ablation,
      elevated levels of IL-6 and hs-CRP before ablation are independent predictors of
      recurrence of AF.

PMID- 19117240
TI  - A characterization in childhood inflammatory bowel disease, a new population
      based inception cohort from South-Eastern Norway, 2005-07, showing increased
      incidence in Crohn's disease.
AB  - OBJECTIVE: Owing to rising incidence rates in inflammatory bowel disease (IBD),
      there has been increased interest in causal relationships in pediatric disease.
      The present population-based inception cohort was recruited in the Oslo area from
      2005 to 2007, with the aim of conducting a detailed characterization of treatment
      naive patients at diagnosis. MATERIAL AND METHODS: After an invitation was
      extended to all general practitioners in the catchment area, patients aged <18
      years with suspected IBD were diagnosed by proximal and distal endoscopy, MRI,
      demographic, clinical, and histological and molecular characteristics.
      Symptomatic non-IBD patients served as controls. RESULTS: Of 100 pediatric
      patients, 62 had IBD (39 Crohn's disease (CD), 19 ulcerative colitis (UC), 4 IBD
      unclassified (IBDU)) and 38 other diseases. Median age at diagnosis for IBD was
      13.1 years (56.4% males), median symptom duration 6 months, and 69% L3 (Vienna
      classification). With 195,000 children aged <18 years in the catchment area, the
      incidence rate of IBD per 100,000/years inhabitants was 10.9 (6.8 for CD, 3.6 for
      UC, and 0.6 IBDU) and for those aged <16 years (178,500) the incidence rate was
      10.6. The higher NOD2 allele frequency among children may partly contribute to
      the increase. CONCLUSIONS: The results indicate a marked rise in the incidence of
      CD in contrast to no increase in UC in South-Eastern Norway, compared with the
      figures from the last 15 years. Time from onset of symptoms to diagnosis still
      represents a challenge for early characterization in IBD.

PMID- 19117241
TI  - Peginterferon alfa-2a relapse rates depend on weight-based ribavirin dosage in
      HCV-infected patients with genotype 1: results of a retrospective evaluation.
AB  - OBJECTIVE: The cumulative dosage of ribavirin per kilogram of body-weight
      prevents relapse and thus is a significant predictor of sustained virological
      response (SVR). Comparison of peginterferon (peg-IFN) alfa-2b/ribavirin and peg
      IFN alfa-2a/ribavirin shows that the rates of SVR are similar, but the rates of
      relapse are significantly lower under the peg-IFN alfa-2b regimen. Depending on
      the weight-based ribavirin dose, patients with >105 kg reach a maximum of 13.2
      mg/kg body-weight ribavirin in the peg-IFN alfa-2b regimen as opposed to only
      11.3 mg/kg in the peg-IFN alfa-2a regimen. The aim of these investigations was to
      determine relapse rates in a retrospective analysis of 98 patients chronically
      infected with hepatitis C virus (HCV) genotype (GT) 1 in relation to the weight
      based ribavirin dose. MATERIAL AND METHODS: All patients completed treatment with
      peg-IFN alfa-2a/ribavirin (1000 mg/d or 1200 mg/d for patients weighing <75 kg or
      > or =75 kg) for 48 weeks. Classification of a low ribavirin dose with <13.2
      mg/kg body-weight was used. Patients with a ribavirin dose > or =13.2 mg/kg were
      compared with those with a dose <13.2 mg/kg. RESULTS: Patients with a ribavirin
      dose > or = 13.2 mg/kg (n=84) showed a relapse rate of 19.0% in contrast to 71.4%
      in patients with a ribavirin dose of <13.2 mg/kg (n=14) (p=0.0013). The SVR rate
      was significantly higher in the > or =13.2 mg/kg ribavirin dosed group (59.5%
      versus 28.6%). CONCLUSIONS: Weight-adapted ribavirin dosing in combination with
      peg-IFN alfa-2a to avoid giving low doses of ribavirin should be evaluated. This
      will minimize relapse, especially in HCV GT 1 patients.

PMID- 19117242
TI  - Randomized controlled trial of endoscopic ultrasound-guided fine-needle sampling
      with or without suction for better cytological diagnosis.
AB  - OBJECTIVE: Endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) is a
      highly accurate method to obtain specific diagnosis in various diseases. The
      optimal method of EUS-guided sampling of material for pathologic diagnosis has
      not been clearly established. The aim of our study was to compare two different
      techniques of EUS-guided sampling of solid masses, using either non-suction or
      suction with a 10-ml syringe. MATERIAL AND METHODS: Patients assessed during a 6
      month period were randomized to three passes of EUS-guided sampling with suction
      (26 patients) or non-suction (26 patients). The samples were characterized for
      cellularity and bloodiness, with a final cytology diagnosis established blindly.
      The final diagnosis was reached either by EUS-FNA if malignancy was definite, or
      by surgery and/or clinical follow-up of a minimum of 6 months in the cases of non
      specific benign lesions. RESULTS: EUS-guided fine-needle sampling with suction of
      solid masses increased the number of pathology slides (17.8+/-7.1 slides for
      suction as compared with 10.2+/-5.5 for non-suction, p=0.0001), without
      increasing the overall bloodiness of each sample. Sensitivity and the negative
      predictive values were higher when suction was applied, as compared to the non
      suction group (85.7% as compared with 66.7%, p=0.05). CONCLUSIONS: This
      prospective randomized study showed that EUS-guided fine-needle sampling of solid
      masses using suction yields a higher number of slides without increasing
      bloodiness. Although, the proportion of target cells was relatively similar
      between the suction and non-suction sampling techniques, the sensitivity and
      negative predictive values of the procedure were significantly higher when
      suction was added.

PMID- 19117243
TI  - Leprosy in sarawak, East malaysian borneo.

PMID- 19117244
TI  - Complicated community acquired pneumonia in children prior to the introduction of
      the pneumococcal conjugated vaccine.
AB  - Increasing prevalence of pleural empyema (PE) complicating community acquired
      pneumonia (CAP) is reported worldwide. We compared hospitalized children with PE
      or non-purulent pleural effusion (NP-PEF) prior to the inclusion of the
      pneumococcal conjugated vaccine (PCV7) in the Israeli immunization schedule. We
      conducted a retrospective analysis of medical files of all children <18 y of age
      hospitalized with either PE or NP-PEF and CAP during 1990-2002. 75 children with
      NP-PEF and 37 with PE were identified. PE annual incidence increased from 0.5 in
      1990 to 4.2 per 100,000 children in 2002. Higher WBC and absolute neutrophils
      counts were found in sera and pleural fluid of PE. The leading pathogens included
      Streptococcus pneumoniae (42%, all penicillin-susceptible) and Staphylococcus
      aureus (23%, all methicillin-susceptible). Blood cultures were positive only in
      children with PE (12/37, 32.4%). Patients with PE presented with higher
      respiratory rate and required longer hospitalization, more PICU admission, and
      more patients needed mechanical ventilation. PE prevalence increased in southern
      Israel during the study period. Streptococcus pneumoniae (62.5% serotype 1) was
      the most common pathogen causing PE before the introduction of PCV7. Future
      introduction of PCV7 or equivalents in the immunization schedule may impact
      clinical presentation and epidemic trends and will require future consideration.

PMID- 19117245
TI  - Cerebrospinal fluid analysis in children with seizures from respiratory syncytial
      virus infection.
AB  - We report 3 cases of respiratory syncytial virus infection-associated seizures;
      their abnormalities of cerebrospinal fluid (increased interleukin-6 and positive
      for virus by highly sensitive assay) were documented. These data revealed that
      neurological involvement might be caused by a direct invasion.

PMID- 19117246
TI  - Surgical site infection due to Aeromonas species: report of nine cases and
      literature review.
AB  - Gastrointestinal and wound infections are the most common clinical presentation
      of Aeromonas. Surgical site infections (SSIs) due to this microorganism are rare.
      We studied the clinical and microbiological characteristics of 9 cases that
      appeared at 2 Spanish hospitals and reviewed 15 cases available in the
      literature. All patients (including our cases) had gastrointestinal or biliary
      diseases. 21 patients (91.3%) developed SSIs after abdominal or pelvic surgery.
      The mean duration from surgery to the onset of wound infection was 2.2 d in our 9
      patients. The infection was polymicrobial in 17 patients (77.2%) and 19 cases
      were nosocomial (95%). Clinical outcome of all cases was uniformly good after
      treatment except for 2 patients. Two patients were cured only with surgical
      drainage. In conclusion, SSIs due to Aeromonas species have a probable endogenous
      source after abdominal or pelvic surgery and the onset is rapid in most cases.
      Clinical outcome is good after antibiotic treatment but surgical drainage without
      antibiotic therapy can be sufficient to clear the infection in some cases.

PMID- 19117247
TI  - Rheumatoid arthritis in UK primary care: incidence and prior morbidity.
AB  - OBJECTIVES: To estimate the incidence of rheumatoid arthritis (RA) in primary
      care and to investigate associations with consultation behaviour, risk factors,
      and comorbidities, using the UK General Practice Research Database (GPRD).
      METHODS: Subjects with a first-ever diagnosis of RA between 1 January 1996 and 31
      December 1997 (n = 579) were identified from a cohort of 1 206 918 subjects aged
      20-79 years without cancer. Controls from the same cohort were frequency-matched
      to the RA group by age, sex, and calendar year (n = 4234). Odds ratios (ORs) and
      95% confidence intervals (CIs) of being diagnosed with RA in association with a
      range of factors were estimated using logistic regression analysis. RESULTS: RA
      incidence was 0.15 per 1000 person-years, was higher in women than in men, and
      increased with age in both sexes. Consultations and use of non-steroidal anti
      inflammatory drugs (NSAIDs) prior to diagnosis were increased in subjects with
      RA. An increased risk of RA was observed in association with anaemia in the
      previous year (OR 2.63, 95% CI 1.54-4.48) and with smoking (1.33, 1.07-1.67). A
      decreased risk of RA was observed in association with infectious diseases (0.68,
      0.50-0.94) and pregnancy in the previous year (0.22, 0.06-0.77), diabetes (0.45,
      0.26-0.78), and hypertension (0.74, 0.57-0.94). We found no association with
      alcohol intake, obesity, or use of low-dose aspirin, oral contraceptives, or
      hormone replacement therapy (HRT). CONCLUSIONS: Smoking was identified as the
      only significant lifestyle-related risk factor for RA. Infection in the previous
      year was associated with a reduced likelihood of RA.

PMID- 19117248
TI  - Occurrence of systemic lupus erythematosus in a Danish community: an 8-year
      prospective study.
AB  - OBJECTIVES: To determine the prevalence and annual incidence of definite systemic
      lupus erythematosus (D-SLE) and incomplete SLE (I-SLE) in a community-based lupus
      cohort of predominantly Nordic ancestry in an 8-year prospective study from 1995
      to 2003, and also to calculate the annual transition rate of I-SLE to D-SLE.
      METHODS: In 1995 all SLE patients in the county of Funen were retrieved from four
      separate and independent sources. Incident cases were subsequently identified by
      surveillance of these sources. RESULTS: During the 8-year study period the median
      annual incidence of D-SLE (1.04 per 100 000) and I-SLE (0.36 per 100 000)
      remained almost constant. The point prevalence (PP) of D-SLE increased from 21.9
      to 28.3 per 100 000, and from 6.19 to 7.53 per 100 000 for I-SLE. During follow
      up, seven I-SLE patients transformed into D-SLE at a progression rate of 3.64 per
      100 person-years at risk [95% confidence interval (CI) 1.44-7.55]. CONCLUSIONS:
      Denmark is a low-incidence lupus area but lupus prevalence is increasing slowly.
      I-SLE is a disease variant that may eventually convert into D-SLE.

PMID- 19117249
TI  - Genital cancer and oral contraceptives. The good news!

PMID- 19117250
TI  - Sexual and reproductive health issues of Turkish immigrants in the Netherlands.
AB  - OBJECTIVE: To identify factors that influence aspects of sexual and reproductive
      health behaviour, such as contraceptive use and teenage pregnancies, among
      Turkish immigrants in the Netherlands. METHOD: This socio-cultural review
      compares data from demographic surveys and opinion studies. The explanation for
      the trends found in these data was sought in the differences between the cultural
      backgrounds of immigrant and host populations, and in the socio-cultural changes
      that people undergo after immigration. DATA: In the Netherlands, 2.3% of the
      population are first- and second-generation Turkish immigrants. These people
      often originate from more traditional or underdeveloped rural areas in Eastern
      and Southern Turkey. Reproductive behaviour in the Netherlands differs greatly
      from that in Eastern and Southern Turkey, especially with regard to the use of
      contraception, abortion and the age at which women have children. These
      differences are largely the result of community-bound sets of opinions and role
      patterns. CONCLUSION: After immigration, the acculturation process will lead to a
      change in behaviour. During this process conflicts in relationships will arise
      within and between first- and second generation Turkish immigrants. These
      conflicts are particularly evident within the second generation that grew up in
      the Netherlands. These persons have adopted a number of opinions prevailing in
      the host country but, at the same time, cling to various traditional values.
      Second-generation Turkish women seem to adapt faster to the new culture than
      their male counterparts.

PMID- 19117251
TI  - Update on nonoxynol-9 as vaginal spermicide.
AB  - Nonoxynol-9 (N-9) is a typical surfactant. For more than 30 years that very
      property of N-9 has been successfully exploited for its spermicidal action. It is
      available as an over-the-counter, locally acting vaginal spermicide. The
      suitability of N-9 as a spermicide is elaborated in this article. The reasons why
      N-9 may fail as a contraceptive are discussed. In spite of many drawbacks, which
      are mentioned in the article, N-9 is still often resorted to as a locally acting
      contraceptive. The review ends with suggestions to alter the molecular structure
      of N-9 and to adjust the dosages.

PMID- 19117252
TI  - Emergency contraception in South Africa: a literature review.
AB  - OBJECTIVES: Since emergency contraception (EC) products became available over the
      counter in South Africa in 2000 a number of studies have emerged. This paper
      reviews the growing body of literature on EC in that country. METHODS: Standard
      computer database searches identified published articles and reports on EC in
      South Africa. RESULTS: The level of awareness of EC is fairly low, especially
      among public sector clients. Most studies suggest that very few people have even
      heard of it. Several studies also indicate that provider knowledge of and
      attitude towards EC vary greatly. While many providers are aware of the
      indications and efficacy of the method, not all health care professionals are
      sufficiently knowledgeable and misperceptions persist. The limited knowledge of
      EC among health professionals may, in turn, prevent them from discussing it with
      clients. CONCLUSION: The existing literature suggests that the greater
      availability of EC is not sufficient to increase uptake and that interventions
      are needed to ensure that women become aware of this option.

PMID- 19117253
TI  - The feasibility of European reproductive health indicators.
AB  - OBJECTIVE: The elaboration of a European health monitoring system is an ongoing
      process. Our aim was to study the availability, feasibility and comparability of
      the reproductive health indicators and to illustrate whether cross-country
      comparisons are feasible for pinpointing areas of concern and future research.
      METHODS: We surveyed 18 reproductive health indicators from eight countries:
      Finland, France, Germany, Italy, Latvia, Poland, Romania and Spain. The data were
      obtained from national sources and international health databases. RESULTS:
      Indicators based on routine health and population statistics and registers were
      available, reliable, and comparable. The only exceptions were the proportion of
      children born after assisted reproductive technology and age-specific teenage
      birth rates, which were less commonly available. There were more problems in
      obtaining comparable information for indicators which are to be taken from health
      surveys. In many cases the data did not exist at all or were old. The
      comparability was also affected by the significant variation in data collection
      methods, inclusion criteria and survey-question wording. Consequently, the
      comparability could not be ascertained with our data. CONCLUSIONS: Health surveys
      seldom include questions on reproductive and sexual health. The European Health
      Interview should include core questions on reproductive and sexual health.

PMID- 19117254
TI  - Etonogestrel implant in women with diabetes mellitus.
AB  - OBJECTIVES: To evaluate the effect of etonogestrel implant on the control of the
      carbohydrate and lipid metabolism and on the progression of vascular
      complications in diabetic women treated with insulin, and to assess the
      acceptability of this modality of contraception in these patients. METHODS:
      Prospective-observational study of 23 women with insulin-treated diabetes.
      Clinical and metabolic evaluation was performed before and at 3, 6, 12, and 24
      months after implant insertion. Changes from baseline were compared using the
      mixed effects models or Wilcoxon matched-pairs signed-rank tests. RESULTS: There
      were no significant changes in BMI, in daily insulin requirement and in mean
      HbA1c. There was a significant reduction of total serum cholesterol (TC) at 6 and
      12 months, of triglyceride levels at 6, 12 and 24 months, and of high-density
      lipoprotein cholesterol (HDL-C) at 6, 12 and 24 months. Neither the low-density
      lipoprotein (LDL) levels nor the HDL/TC ratio changed. Albuminuria decreased
      significantly at 12 and 24 months. No deterioration of the retina was observed
      over the study period. Amenorrhoea and infrequent bleeding were the most common
      menstrual bleeding patterns. One woman discontinued the method due to frequent
      bleeding. CONCLUSION: We found no evidence of impaired control of the
      carbohydrate and lipid metabolism or aggravation of vascular lesions during the
      two years an etonogestrel implant was used by diabetic women.

PMID- 19117255
TI  - Women's awareness of long-acting, reversible contraceptive methods (LARCs) in
      community family planning clinics and general practice.
AB  - OBJECTIVES: To investigate whether awareness and choice of long-acting reversible
      contraceptives (LARCs) of women attending a community family planning clinic
      differ from those of women seeing general practitioners (GPs). METHODS:
      Information was collected from women in their reproductive years about their
      current contraceptive method, their awareness of LARCs and whether they felt well
      informed about their options. After additional information was provided the
      respondents were asked whether they would consider changing their method and if
      their GP offered this option. RESULTS: Questionnaires were completed by 177 women
      attending a city-centre contraception and sexual health (CASH) clinic (n = 96)
      and a GP's surgery in a neighbouring city (n = 81). Forty percent of women in the
      CASH cohort and 6% in the primary care group were using LARCs. Women attending
      the CASH service were more aware of their contraceptive options and felt better
      informed but less than 50% in either group had heard of the levonorgestrel
      releasing intrauterine system. At least 50% of women would consider using a LARC
      yet few knew if their GP fitted/provided these methods. CONCLUSION: LARC usage
      was considerably higher in CASH services compared to primary care. Those
      providing contraceptive care should give up-to-date information covering all
      methods and referral to local specialist services, as appropriate.

PMID- 19117256
TI  - Male partner involvement and assistance in female condom use.
AB  - OBJECTIVE: To investigate how males assist their partners in using the female
      condom. METHODS: A multi-site, randomized, cross-over trial was conducted to test
      the performance and acceptability of the Reality female condom compared to a
      prototype similar in design and appearance but made of synthetic latex (FC2). In
      this study women were asked about male partner assistance in FC use. RESULTS:
      Partner assistance in FC use was similar across FC type. Of the women who
      returned for the first follow-up visit (n = 233), just over a third (35.2%)
      reported that the male partner assisted in the insertion compared to 26.4% of the
      201 women who returned for the second visit. In most cases where the partner
      assisted, the device was inserted using the inner ring, as recommended in the
      instructions for use. A small number (6%) mentioned that partners assisted in
      removal. CONCLUSION: Men have a role to play in the use of the female condom and
      are willing to assist their partners in using it.

PMID- 19117257
TI  - The role of parity in medical abortion up to 49 days of amenorrhoea.
AB  - OBJECTIVE: To identify possible risk factors for failure of medical abortion.
      METHOD: Retrospective study of data collected between 1 January 2001 and 31
      December 2005, concerning 1850 women who, for medical abortion up to 49 days of
      amenorrhoea, had received 600 mg oral mifepristone followed 48 h later by 400
      microg oral misoprostol and, if necessary, a second oral dose of 400 microg.
      RESULTS: The method was effective in 97.1% of cases. Fifty four failures (2.9%)
      were recorded, including seven continuing pregnancies (0.4%). The global efficacy
      rate of this mifepristone-misoprostol regimen is among the best using similar
      treatment protocols. The proportion of failures augmented with parity.
      CONCLUSION: This study suggests that parity is a major factor influencing the
      success of medical abortion. A greater parity of the patients was associated with
      a lower efficacy of treatment.

PMID- 19117258
TI  - Determinants of choosing withdrawal over modern contraceptive methods in Turkey.
AB  - OBJECTIVES: The determinants of the use of withdrawal in Turkey are examined
      using a multinomial logistic model. METHODS: Data were drawn from a nation-wide
      population-based cross-sectional study, the Turkish Demographic Health Surveys
      that took place in 1998 and 2003. Detailed interviews were conducted with 8576
      women aged 15-49 and analysed using SPSS. RESULTS: Contextual, cultural and
      demographic characteristics define women's choice of withdrawal over modern
      methods. Socio-economic status, education, employment status, and past fertility
      behaviour are among key determinants. First-ever used contraception method has a
      very strong impact on later choices. Urban women, the more educated, those with
      better socioeconomic status, and those living in less crowded households resort
      less to withdrawal. Experience and empowerment positively linked to modern
      contraceptive use among women in Turkey. CONCLUSIONS: The use of contraceptive
      methods in Turkey differs greatly. Empowerment of women in terms of better
      socioeconomic status, better education, modern and liberal attitudes towards
      women and family planning seem to reduce withdrawal use as the main method of
      contraception. The results suggest the need for education (particularly targeting
      young women and couples), information and provision of modern contraceptive
      services particularly for disadvantaged groups.

PMID- 19117259
TI  - Socio-demographic factors influence contraception use among female students of
      the University of Novi Sad (Serbia).
AB  - OBJECTIVES: To identify some of the socio-demographic factors that influence the
      use of contraception among female university students and to gain a deeper
      insight into their contraceptive behaviour. METHODS: The study encompassed 597
      randomly chosen, sexually active, second- and third-year female students of the
      University of Novi Sad (Serbia). The questionnaire, specially designed for the
      purpose of this investigation, covered a number of socio-demographic factors that
      could presumably influence the contraceptive behaviour of the polled students.
      RESULTS: Statistically significant differences among the respondents with respect
      to contraception use appeared to be: mother's education, presence of an elder
      sibling in the family, motivation for engaging in sexual intercourse, talking
      with friends, as well as self-assessment of the knowledge about contraception.
      CONCLUSION: The identified socio-demographic factors that influence the
      contraceptive behaviour of female students should allow to devise appropriate
      strategies for the promotion of the use of contraception by this young
      population.

PMID- 19117260
TI  - Vascular endothelial growth factor (VEGF) and inducible nitric oxide synthase
      (iNOS) immunoreactivities in rat ovaries and uterine tubes after tubal ligation:
      a controlled immunohistochemical study.
AB  - OBJECTIVE: To evaluate the effects of tubal ligation on ovarian and tubal tissues
      by means of immunohistochemical evaluation of two hypoxia related mediators:
      vascular endothelial growth factor (VEGF) and inducible nitric oxide synthase
      (iNOS). DESIGN: Fourteen Sprague-Dawley female rats were divided into two groups:
      a tubal ligation (Pomeroy technique) was carried out on rats in group 1 (n = 7)
      whereas those in group 2 served as controls (n = 7). Salpingo-oophorectomy was
      performed in group 1 during the second oestrous period following tubal ligation.
      Rats in group 2 were submitted to a salpingo-oophorectomy, as well. VEGF and iNOS
      immunoreactivities in ovarian and tubal tissues were evaluated by means of
      immunohistochemistry. Immunohistochemical scores and number of antral follicles
      were compared. RESULTS: In the ovary, VEGF immunoreactivity was significantly
      more intense in the granulosa (p = 0.002) and the theca cells (p = 0.001) of rats
      in group 1 but, in ovarian medulla (p = 0.259) and germinal epithelium (p =
      0.209), it was not significantly different from that of rats in group 2. The iNOS
      immunoreactivity in ovarian granulosa cells (p = 0.073) and germinal epithelial
      cells (p = 0.805) did not differ between the two groups. The cytoplasmic VEGF (p
      = 0.001) and iNOS (p = 0.017) immunoreactivities in the uterine tube, were
      significantly more intense in group 1. However, VEGF immunoreactivity in the
      lamina propria of the uterine tube (p = 0.209) was of similar intensity in both
      groups. CONCLUSION: Tubal ligation may lead to supraphysiological hypoxia as
      evidenced by increased VEGF and iNOS immunoreactivities in ovarian and tubal
      tissues.

PMID- 19117263
TI  - Incidence of thin basement membrane nephropathy in 990 consecutive renal biopsies
      examined with electron microscopy.
AB  - Thin basement membrane nephropathy is one of the main causes of hematuria in both
      children and adults. It is often associated with a family history and its true
      incidence is unknown. Accurate diagnosis of thin basement membrane nephropathy
      relies on the presence of attenuated glomerular basement membranes, a finding
      that can be appreciated only by examination in the electron microscope. In Cyprus
      the department of electron microscopy has received 990 consecutive renal biopsies
      for diagnosis. The aim of this study is to define the incidence of thin basement
      membrane nephropathy in this population sample based on the results of electron
      microscopy.

PMID- 19117264
TI  - New diagnostic and molecular characteristics of malignant mesothelioma.
AB  - Malignant mesothelioma is a primary cancer of the serosal cavities, an anatomic
      site that is also frequently affected by metastatic disease, predominantly from
      primary carcinomas of the lung, breast, and ovary. Advances in
      immunohistochemistry have resulted in improved diagnostic sensitivity and
      specificity in the differential diagnosis between metastatic adenocarcinoma and
      malignant mesothelioma in both cytological and histological material. Recently,
      the author's group applied high throughput technology to the identification of
      new markers that may aid in differentiating malignant mesothelioma from ovarian
      and peritoneal serous carcinoma, tumors with closely related histogenesis and
      antigenic profile. In addition to the improved tools available for serosal cancer
      diagnosis, knowledge regarding the biology of malignant mesothelioma has been
      accumulating in recent years. This review presents current data regarding the
      diagnostic and biological aspects of malignant mesothelioma.

PMID- 19117265
TI  - Ultrastructural studies of glioma stem cells/progenitor cells.
AB  - Although the ultrastructural features of several brain tumor cells have been
      studied in details, the ultrastructure of glioma stem cells/progenitors cells
      (GSPC) has rarely been reported. In this paper, the authors describe the
      ultrastructural features of GSPCs isolated from both a glioma tissue and the
      human glioma cell SHG-44 cell line. The ultrastructural features of the two kinds
      of GSPCs were similar, with relatively developed mitochondria, Golgi apparatuses,
      ribosomes, undeveloped rough endoplasmic reticula, seldom lysosomes and no
      typical autophagosomes, and high nuclear-cytoplasmic ratio. Their nuclei,
      frequently containing huge amounts of euchromatin and a small quantity of
      heterochromatin, were mostly globular; and the majority of the nuclei had only
      one nucleole. Typical apoptotic cells could hardly be found in tumor spheres, and
      between adjacent cells there were cell junctions, which probably were
      incompletely developed desmosomes or intermediate junctions. In conclusion, their
      ultrastructural features showed that GSPCs were at the primary stage of
      differentiation, and could even partially reveal the underlying reasons for the
      malignant proliferation and differential inhibition of GSPCs.

PMID- 19117266
TI  - BACE2 is stored in secretory granules of mouse and rat pancreatic beta cells.
AB  - BACE2 is a protease homologous to BACE1 protein, an enzyme involved in the
      amyloid formation of Alzheimer disease (AD). However, despite the high homology
      between these two proteins, the biological role of BACE2 is still controversial,
      even though a few studies have suggested a pathogenetic role in sporadic
      inclusion-body myositis and hereditary inclusion-body myopathy, which are
      characterized by vacuolization of muscular fibers with intracellular deposits of
      proteins similar to those found in the brain of AD patients. Although BACE2 has
      also been identified in the pancreas, its function remains unknown and its
      specific localization in different pancreatic cell types has not been
      definitively ascertained. For these reasons, the authors have investigated the
      cellular and subcellular localization of BACE2 in normal rodent pancreases. BACE2
      immunoreactivity was found in secretory granules of beta cells, co-stored with
      insulin and IAPP, while it was lacking in the other endocrine and exocrine cell
      types. The presence of BACE2 in secretory granules of beta cells suggests that it
      may play a role in diabetes-associated amyloidogenesis.

PMID- 19117267
TI  - Renal medullary carcinoma: ultrastructural studies may benefit diagnosis.
AB  - Renal medullary carcinoma is a recently described highly aggressive malignancy
      that in most instances exhibits a constellation of clinical and light microscopic
      features sufficiently distinctive to enable a quick and confident diagnosis.
      Presented are three examples where, because of unusual elements in the clinical
      presentation, electron microscopic examination proved beneficial in establishing
      the diagnosis.

PMID- 19117271
TI  - Evaluation of a cancer exercise program: patient and physician beliefs.
AB  - OBJECTIVE: Participation in an exercise intervention during cancer treatment
      diminishes the side effects associated with cancer therapies, although such
      benefits vary according to the disease and the patient characteristics. A
      structured exercise program providing an individualized fitness program tailored
      to the patients' illness, treatment, and fitness level would address this
      variability. However, the need, desired components, and anticipated barriers of
      such a program have not been systematically explored from either the point of
      view of cancer patients or treating oncologists. METHODS: Sixty-six cancer
      patients and 18 medical and radiation oncologists were surveyed on the above
      variables. RESULTS: Cancer patients and oncologists alike perceived a need for a
      structured exercise program during and after medical treatment for cancer. Among
      cancer patients, the most commonly preferred feature was access to consultation
      with an exercise specialist who could take into account the patient's previous
      exercise and medical history. Over a third of patients reported interest in a
      hospital-based fitness program. Oncologists were in favor of appropriate
      supervision of patients during exercise, and noted insufficient time to discuss
      exercise in their practice. Respondents noted time and parking as barriers to
      participation. CONCLUSION: Overall, results support the need for a supervised
      exercise program during active treatment for cancer and highlight the desired
      features of such a program.

PMID- 19117272
TI  - Modification of native collagen with cell-adhesive peptide to promote RPE cell
      attachment on Bruch's membrane.
AB  - Current efforts to reverse loss of visual function due to Age-related Macular
      Degeneration point to the restoration of the Retinal Pigment Epithelial (RPE)
      layer. Restoration of the RPE layer involves replacing lost RPE cells as well as
      addressing the degeneration of the underlying Bruch's membrane (BM). To advance
      the potential of using donor BM, we present a strategy to achieve specific and
      controllable modification of the inner collagenous layer (ICL) of the Bruch's
      membrane. In particular, interaction between a collagen binding peptide (CBP)
      sequence with exposed collagen fibers on the ICL surface is utilized to anchor
      bioactive molecules. Here, a cell-adhesion sequence is added to the collagen
      binding sequence to promote attachment and survival of ARPE-19. First, the
      binding specificity of the CBP sequence is verified with a fluorescent binding
      assay. Subsequently, the effect of modification using the peptide is studied
      qualitatively using confocal fluorescent imaging and quantitatively through a
      cell proliferation assay. Results of these experiments indicate that the peptide
      sequence binds specifically to collagen fibers. Additionally, modification using
      the peptide enhanced cell adhesion, allowing large uniform cell networks to be
      formed on the surface. Furthermore, modification with the peptide also delayed
      the onset of apoptosis on adherent cells.

PMID- 19117273
TI  - Assessment of fetal canine cardiac myocyte survival in a dual-side flow
      bioreactor with modeled hypoxia/reperfusion injury.
AB  - The present study introduces a new experimental model of hypoxia/reperfusion
      injury using a newly developed bioreactor system. The injury is introduced and
      kept localized via fluid dynamic manipulation. Using low Reynolds number fluid
      flow, regions of the culture can be injured while maintaining physiological
      conditions in the remaining culture. This approach enables both normal and
      injured cells within the same monolayer to be investigated side-by-side. The
      current study evaluated the ability of the model to induce localized reperfusion
      injury in a monolayer of fetal canine cardiomyocytes (FCCs). Significant
      apoptosis was found in the hypoxia/reperfusion-injured but not normal-flow
      regions of the myocyte cultures. The model holds the potential to help elucidate
      the fundamental mechanisms of hypoxic/reperfusion insults in myocardium.

PMID- 19117274
TI  - Neural correlates of resolving uncertainty in driver's decision making.
AB  - Neural correlates of driving and of decision making have been investigated
      separately, but little is known about the underlying neural mechanisms of
      decision making in driving. Previous research discusses two types of decision
      making: reward-weighted decision making and cost-weighted decision making. There
      are many reward-weighted decision making neuroimaging studies but there are few
      cost-weighted studies. Considering that driving involves serious risk, it is
      assumed that decision making in driving is cost weighted. Therefore, neural
      substrates of cost-weighted decision making can be assessed by investigation of
      driver's decision making. In this study, neural correlates of resolving
      uncertainty in driver's decision making were investigated. Turning right in left
      hand traffic at a signalized intersection was simulated by computer graphic
      animation based videos. When the driver's view was occluded by a big truck, the
      uncertainty of the oncoming traffic was resolved by an in-car video assist system
      that presented the driver's occluded view. Resolving the uncertainty reduced
      activity in a distributed area including the amygdala and anterior cingulate.
      These results implicate the amygdala and anterior cingulate as serving a role in
      cost-weighted decision making.

PMID- 19117276
TI  - Repetition suppression for performed hand gestures revealed by fMRI.
AB  - The functional components of the human motor system that are used to retrieve and
      execute simple intransitive hand gestures were identified with a repetition
      suppression (RS) paradigm. Participants performed movements with the right hand
      to text instructions in a rapid event related design with a pseudo-random
      stimulus order. Brain areas associated with action retrieval were identified by
      comparing trials where an action was repeated to trials that involved a new
      action. Performance of a novel action, collapsed across individual actions,
      resulted in significantly greater activity in a left hemisphere predominant
      fronto-parietal circuit involving inferior frontal gyrus and inferior parietal
      cortex (supramarginal gyrus). This is consistent with previous action retrieval
      tasks using go, no-go paradigms and lesion studies of patients with apraxia that
      emphasize a role of these areas in action organization. In addition, RS effects
      were present in left primary sensorimotor cortex. These effects cannot be
      ascribed to kinematic differences, simple action related activity or differences
      of cognitive set. Significant RS effects for action retrieval could be identified
      with as little as 5 min of fMRI data and underscores the potential of using RS to
      characterize representational structure within the motor system.

PMID- 19117275
TI  - Improved EEG source analysis using low-resolution conductivity estimation in a
      four-compartment finite element head model.
AB  - Bioelectric source analysis in the human brain from scalp electroencephalography
      (EEG) signals is sensitive to geometry and conductivity properties of the
      different head tissues. We propose a low-resolution conductivity estimation
      (LRCE) method using simulated annealing optimization on high-resolution finite
      element models that individually optimizes a realistically shaped four-layer
      volume conductor with regard to the brain and skull compartment conductivities.
      As input data, the method needs T1- and PD-weighted magnetic resonance images for
      an improved modeling of the skull and the cerebrospinal fluid compartment and
      evoked potential data with high signal-to-noise ratio (SNR). Our simulation
      studies showed that for EEG data with realistic SNR, the LRCE method was able to
      simultaneously reconstruct both the brain and the skull conductivity together
      with the underlying dipole source and provided an improved source analysis
      result. We have also demonstrated the feasibility and applicability of the new
      method to simultaneously estimate brain and skull conductivity and a
      somatosensory source from measured tactile somatosensory-evoked potentials of a
      human subject. Our results show the viability of an approach that computes its
      own conductivity values and thus reduces the dependence on assigning values from
      the literature and likely produces a more robust estimate of current sources.
      Using the LRCE method, the individually optimized four-compartment volume
      conductor model can, in a second step, be used for the analysis of clinical or
      cognitive data acquired from the same subject.

PMID- 19117277
TI  - Increased self-focus in major depressive disorder is related to neural
      abnormalities in subcortical-cortical midline structures.
AB  - Patients with major depressive disorder (MDD) often show a tendency to strongly
      introspect and reflect upon their self, which has been described as increased
      self-focus. Although subcortical-cortical midline structures have been associated
      with reflection and introspection of oneself in healthy subjects, the neural
      correlates of the abnormally increased attribution of negative emotions to
      oneself, i.e. negative self-attribution, as hallmark of the increased self-focus
      in MDD remain unclear. The aim of the study was, therefore, to investigate the
      neural correlates during judgment of self-relatedness of positive and negative
      emotional stimuli thereby testing for emotional self-attribution. Using fMRI, we
      investigated 27 acute MDD patients and compared them with 25 healthy subjects
      employing a paradigm that focused on judgment of self-relatedness when compared
      with mere perception of the very same emotional stimuli. Behaviourally, patients
      with MDD showed significantly higher degrees of self-relatedness of specifically
      negative emotional stimuli when compared with healthy subjects. Neurally,
      patients with MDD showed significantly lower signal intensities in various
      subcortical and cortical midline regions like the dorsomedial prefrontal cortex
      (DMPFC), supragenual anterior cingulate cortex, precuneus, ventral striatum (VS),
      and the dorsomedial thalamus (DMT). Signal changes in the DMPFC correlated with
      depression severity and hopelessness whereas those in the VS and the DMT were
      related to judgment of self-relatedness of negative emotional stimuli. In
      conclusion, we present first evidence that the abnormally increased negative self
      attribution as hallmark of the increased self-focus in MDD might be mediated by
      altered neural activity in subcortical-cortical midline structures.

PMID- 19117278
TI  - Postconcussion syndrome after minor head injury: brain activation of working
      memory and attention.
AB  - After minor head injury (MHI) postconcussive symptoms (PCS) such as memory and
      attention deficits frequently occur. It has been hypothesised that PCS are caused
      by microstructural damage to the brain due to shearing injury, which is not
      detectable with conventional imaging, and may be responsible for a functional
      deficit. The purpose of this study was to correlate functional magnetic resonance
      imaging brain activation of working memory and selective attention with PCS. 21
      MHI patients and 12 healthy controls were scanned at 3T. Stimulation paradigms
      were the n-back and Counting Stroop tasks to engage working memory and selective
      attention, respectively. Functional data analysis consisted of random effects
      group analyses, correlating brain activation patterns with the severity of PCS as
      evaluated with the Rivermead postconcussion symptoms questionnaire. At minimal
      working memory load, activation was seen in patients with greater severity of PCS
      in the working memory network. With an increase of working memory load, increase
      of activation was more pronounced in patients with greater severity of PCS. At
      high and increased working memory load, activation associated with the severity
      of PCS was seen in the posterior parietal area, parahippocampal gyrus, and
      posterior cingulate gyrus. Activation related to selective attention processing
      was increased with greater severity of PCS. The increased activity in relation to
      working memory and attention, and the recruitment of brain areas outside the
      working memory network at high working memory load, may be considered a
      reflection of the brain's compensatory response to microstructural injury in
      patients with PCS.

PMID- 19117279
TI  - The report of coping strategies and psychosocial adjustment in Korean mothers of
      children with cancer.
AB  - OBJECTIVE: Parents of children with cancer must cope with multiple challenges
      over time. As most research on parental coping has been conducted in Western
      countries, little information is available on the parental experience of coping
      in non-Western countries. Using a new cultural sample of Korean mothers, this
      study describes their coping strategies. In addition, the association of
      particular coping patterns with mothers' report of psychosocial adjustment is
      investigated. METHODS: A total of 200 Korean mothers of children with cancer
      participated in the study. Coping strategies were measured by the Coping Health
      Inventory for Parents in the following three categories: Maintaining Family
      Integration and an Optimistic Outlook for the Situation, Seeking Social Support,
      and Seeking Information. Maternal psychosocial adjustment was measured by
      psychological distress, family relationship, and social relationship subscales
      from the Psychosocial Adjustment to Illness Scale. RESULTS: Korean mothers
      reported coping strategies related to Maintaining Family Integration and an
      Optimistic Outlook for the Situation as being most helpful. More frequent use of
      coping pattern, Maintaining Family Integration and an Optimistic Outlook for the
      Situation, and less frequent use of coping pattern, Information-Seeking were
      significantly associated with lower psychological distress and better family
      relationship after children's medical and maternal characteristics were
      controlled for. Coping pattern, Seeking Social Support was only predictive of
      social relationships. CONCLUSIONS: This study suggests that culture may play a
      significant role in the report of coping among Korean mothers. Future studies
      should consider culturally preferred coping methods and available resources as
      they relate to different adjustment outcomes.

PMID- 19117281
TI  - Drilling speaking valves: a modification to improve vocalization in tracheostomy
      dependent children.
AB  - Pediatric tracheostomy dependence is associated with a variety of sequelae.
      Vocalization delay is commonplace and may result in long-term communication
      disability. Passy-Muir speaking valves are routinely used to allow such children
      to vocalize. Unfortunately, not all tracheostomy dependent children can tolerate
      the placement of a speaking valve. Elevated transtracheal pressures are often
      associated with failure. We describe a method of modifying a standard Passy-Muir
      valve to decrease transtracheal pressures and thus improve tolerance of the
      valve. In our practice, the modification allows a broader range of children
      experience the benefit of speaking valve placement.

PMID- 19117282
TI  - Prolonged stenting of the frontal sinus.
AB  - OBJECTIVES: Stenting of the frontal sinus outflow tract is occasionally used
      following surgery to prevent stenosis. The optimal length of stent retention has
      not been defined and some experts advocate up to 6 months prior to removal. The
      tolerance of even longer periods of stenting is unknown. STUDY DESIGN:
      Retrospective review. METHODS: We identified adult patients in a tertiary
      rhinology practice with frontal sinus stents placed between July 2000 and
      December 2006 and in place at least 6 months. Length of stenting and condition at
      last follow-up were determined. RESULTS: : During the 6-year study period, 10
      frontal sinus stents were placed out of over 450 endoscopic frontal sinus surgery
      procedures. Each patient had only one stent placed. Of these 10 patients, one was
      excluded because the stent was electively removed at eight weeks. None of the
      remaining nine has been lost to follow-up. The mean length of stenting was 32.6
      months (median 17, range 11 to 73). One patient had the stent removed at 61
      months because of infection. Another had the stent removed at 11 months because
      of pain and edema. The remaining seven patients remain asymptomatic with patent
      stents and no granulation tissue seen on nasal endoscopy. CONCLUSIONS: In this
      group, long-term frontal stenting was rarely used but relatively well tolerated
      with only two of nine patients requiring removal up to 6 years after placement.
      With the optimal length for frontal stenting unknown, risks and benefits of
      removal at each evaluation point must be weighed.

PMID- 19117283
TI  - Validation of a laryngeal dissection module for phonomicrosurgical training.
AB  - OBJECTIVES: To validate the use of a new phonomicrosurgical trainer called the
      laryngeal dissection module. STUDY DESIGN: The module used synthetic,
      multilayered vocal folds inside a model larynx mounted on a platform, a
      microscope, and microsurgical instruments. The study was designed to test the
      module's ability to differentiate novices from expert surgeons and to test the
      module's ability to improve novice performance with training. METHODS: Expert (n
      = 5) and novice (n = 21) phonomicrosurgeons were instructed to remove a
      superficial ovoid lesion from a synthetic, right vocal fold. The task was
      assessed for total errors, total operating time, and injury to the superficial
      peripheral tissue, the lesion, and the deep tissue. Novice and expert performance
      was compared using an independent samples t test and a Fisher exact test.
      Subsequently, novices completed three practice trials and a posttraining trial,
      which was assessed for improvement compared with pretraining performance using a
      Wilcoxon signed rank test. RESULTS: Experts completed the task with fewer total
      errors than novices (P < .001) and made fewer injuries to the oval lesion (P =
      .01). Novices improved performance with training, making fewer total errors in
      the posttraining trial (P = .003), reducing injury to the superficial peripheral
      tissue (P = .02), and taking less time to complete the task (P = .04).
      CONCLUSIONS: The laryngeal dissection module was validated as a surgical trainer.
      It was able to differentiate expert versus novice performance, and it improved
      novice performance through training.

PMID- 19117284
TI  - Evolution of endoscopic surgical therapy for Zenker's diverticulum.
AB  - Zenker's diverticulum is a rare anatomic defect that physicians have confronted
      for almost 250 years. Its location at the interface of the pharynx, neck, and
      mediastinum makes surgical access difficult and risks severe morbidity. Minimally
      invasive endoscopic surgical repair of Zenker's diverticulum has been attempted
      for more than a century as an alternative to reduce morbidity of an open
      transcervical approach. However, limitations due to available antibiotics,
      instrumentation, and laryngoscopes, as well as a general discomfort with a
      sutureless closure of the mucosal excision, have delayed widespread adoption of
      minimally invasive repair until the last 10 to 15 years. This manuscript will
      detail the historical evolution of endoscopic surgical therapy for Zenker's
      diverticulum and highlight the work of two otolaryngologists, Chevalier Jackson
      and Gosta Dohlman, who were critical in advancing the surgical technique and
      reducing morbidity. Lastly, this manuscript will analyze the delay in widespread
      application of endoscopic surgical repair of Zenker's diverticulum.

PMID- 19117285
TI  - The effect of multilevel upper airway surgery on continuous positive airway
      pressure therapy in obstructive sleep apnea/hypopnea syndrome.
AB  - OBJECTIVE: To investigate the effect of multilevel upper airway surgery (USA) on
      subsequent continuous positive airway pressure (CPAP) therapy in patients with
      obstructive sleep apnea/hypopnea syndrome (OSAHS). STUDY DESIGN: Fifty-two
      patients who underwent multilevel UAS with persistent symptoms of OSAHS represent
      the cohort for this study. All patients had undergone manual CPAP titrations both
      pre- and postoperatively. Patients were used as their own controls and were
      compared pre- and postoperatively with regard to body mass index, full night
      polysomnography (PSG), optimal CPAP pressure settings, presence of rapid eye
      movement (REM) sleep, identification of mouth leakage, and CPAP compliance.
      RESULTS: Postoperative values for apnea index (AI), apnea hypopnea index (AHI),
      and minimum oxygen saturation (min SaO(2)) were all significantly decreased from
      their preoperative levels. Compliance with CPAP therapy significantly increased
      from a mean 0.02 +/- 0.14 hours per night prior to surgery to a 3.2 +/- 2.6 hours
      per night following surgery (P < .001). In addition, the optimal CPAP pressure
      setting decreased significantly for a preoperative value of 10.6 +/- 2.1 cm H(2)O
      to 9.8 +/- 2.1 cm H(2)O following surgery. Fifty of the 52 patients (96.2%)
      studied were able to maintain optimal pressure settings without mouth leak,
      postoperatively. CONCLUSIONS: In this study, most patients who had persistent
      symptoms of OSAHS after multilevel UAS did not have significant mouth leak that
      would preclude CPAP therapy. In this cohort of patients, CPAP pressure setting as
      well as compliance was significantly improved postoperatively.

PMID- 19117286
TI  - Minimally invasive endoscopic pericranial flap: a new method for endonasal skull
      base reconstruction.
AB  - OBJECTIVES: One of the major challenges of cranial base surgery is reconstruction
      of the dural defect. Following a craniofacial resection, the standard
      reconstructive technique is direct suture repair of the dural defect with a
      fascial graft and rotation of an anteriorly based pericranial scalp flap to cover
      the dura. The introduction of endoscopic techniques and an endonasal approach to
      the ventral skull base has created new challenges for reconstruction. The
      nasoseptal flap has become the workhorse for vascularized endoscopic skull base
      reconstruction; however at times, the septal mucosal flap may be unavailable for
      reconstruction. This can be due to prior surgical resection or involvement of the
      nasal septum by sinonasal cancer. We have developed a minimally invasive
      endoscopic pericranial flap for endoscopic skull base reconstruction. The use of
      a pericranial scalp flap for reconstruction during endonasal skull base surgery
      using minimally invasive techniques has not been previously reported. METHODS: We
      performed cadaveric studies to illustrate feasibility of an endoscopic
      pericranial flap for endonasal skull base reconstruction, then applied this novel
      technique to an elderly patient after endonasal skull base and dural resection of
      an esthesioneuroblastoma. RESULTS: The technical report of the minimally invasive
      pericranial flap is outlined and the advantages and limitations during endonasal
      skull base reconstruction are discussed. The patient had excellent healing of her
      skull base and had no evidence of any postoperative cerebrospinal fluid leak.
      CONCLUSIONS: The minimally invasive endoscopic pericranial flap provides another
      option for endonasal reconstruction of cranial base defects. There is minimal
      donor site morbidity, and it provides a large flap that can cover the entire
      ventral skull base. The issues of intranasal tissue tumor involvement and the
      need for radiotherapy make the endoscopic pericranial flap an ideal
      reconstruction for anterior cranial base defects resulting from endonasal
      sinonasal and skull base cancer resections.

PMID- 19117287
TI  - Comparison of three common tonsillectomy techniques: a prospective randomized,
      double-blinded clinical study.
AB  - OBJECTIVE: To evaluate three current tonsillectomy techniques--intracapsular
      microdebridement, intracapsular coblation, and traditional extracapsular
      electrocautery dissection--comparing surgical parameters, efficacy, and morbidity
      in the treatment for obstructive sleep disordered breathing in children. STUDY
      DESIGN: Prospective, double-blinded study with follow-up by telephone interview.
      METHOD: From February 2004 to July 2006, a total of 156 patients between the ages
      of 6 months and 22 years scheduled for adenotonsillectomy were randomly assigned
      to electrocautery, coblator, and microdebrider groups. OUTCOME MEASURES: 1)
      Patient demographics; 2) Intraoperative time; 3) Surgeon's perception of
      difficulty; 4) Indicators of postoperative morbidity: pain, use of pain
      medication, return to diet, and activity level; 5) Complications; 6) Cost.
      RESULTS: Microdebrider technique produced the shortest total surgical time,
      averaging 16 minutes. Use of coblation resulted in 2 less days of pain medication
      compared to electrocautery. Patients in the coblator and microdebrider groups
      returned to a normal diet 1.51 days and 1.77 days earlier, respectively, than in
      the electrocautery group. They also returned to preoperative activity levels 1.85
      days and 2.06 days earlier than in the electrocautery group. Of all three
      methods, the microdebrider was the most cost effective. The coblator and
      microdebrider did not differ significantly from each other in all other
      parameters. The three techniques showed no statistically significant difference
      in assessment of difficulty, average pain scores, or postoperative complications.
      CONCLUSIONS: Postoperative recovery following intracapsular adenotonsillectomy in
      children with obstructive sleep apnea is significantly earlier with use of either
      the coblator or microdebrider versus traditional extracapsular tonsillectomy with
      electrocautery. Microdebrider and coblator were comparable in all other areas
      except for shorter operative time and less cost for the microdebrider.

PMID- 19117289
TI  - Would Dr. Ogura approve of endoscopic resection of esthesioneuroblastomas? An
      analysis of endoscopic resection data versus that of craniofacial resection.

PMID- 19117288
TI  - Subcutaneous implants coated with tissue-engineered cartilage.
AB  - OBJECTIVE: To investigate the ability to coat two alloplastic implants, porous
      high-density polyethylene (PHDPE) and expanded polytetrafluoroethylene (e-PTFE),
      with tissue-engineered cartilage (TEC) from human septal chondrocytes in a mouse
      model. STUDY DESIGN: Prospective study. METHODS: PHDPE and e-PTFE disks were
      coated with alginate impregnated with human septal chondrocytes and implanted
      into athymic nude mice. A control group consisting of PHDPE and e-PTFE disks
      coated with alginate only were implanted. Gross, histological, and biochemical
      characteristics of the TEC constructs were examined at 10 and 20 weeks following
      implantation. RESULTS: One animal in the experimental group and one animal in the
      control group died. Implants coated with TEC were successfully generated in 18
      (94.7%) mice in the experimental group (n = 19) and in zero (0%) of the control
      group (n = 17). The final weight of each harvested specimen decreased in the
      control group and increased in the experimental group, when compared with
      preimplant weight. Mean decrease in weight in the control group was greater at 20
      weeks than at 10 weeks (P = .017). Mean increase in weight in the experimental
      group was greater at 20 weeks than at 10 weeks (P = .009). The diameter of the
      control group decreased, while the diameter of the experimental group was
      maintained. The reduction in diameter was less in the experimental group than in
      the control group at 10 (P = .018) and 20 weeks (P = .01). Gross and histological
      examination confirmed the formation of neocartilage, with characteristics similar
      to native cartilage, in the experimental group at 10 and 20 weeks.
      Glycosaminoglycan content in the experimental group at 20 weeks was approximately
      80% of that measured in implanted human septal cartilage. Cartilaginous and
      fibrovascular ingrowth into implant pores was more extensive in the PHDPE than
      the e-PTFE experimental group. CONCLUSIONS: Implants coated with TEC from human
      septal cartilage can be reliably produced in the athymic nude mouse model.
      Maintenance of shape, as measured by the conservation of construct diameter, is
      possible. Fibrovascular ingrowth and cartilage formation into the pores of the
      alloplastic implants was observed. This integration of a construct composed of a
      synthetic implant coated with TEC may improve the performance of alloplastic
      implants through better long-term fixation and increased resistance to infection.

PMID- 19117290
TI  - Reflux as a cause of tracheoesophageal puncture failure.
AB  - OBJECTIVE: To evaluate the response to empiric reflux management in treatment of
      tracheoesophageal punctures (TEP) failures. METHODS: A retrospective chart review
      of patients with failed TEP was performed (n = 37). Only those patients without
      any documented anatomic cause for failure (n = 22) were then further reviewed to
      determine if empiric treatment for reflux improved voicing. Evidence of reflux
      was determined by either using video flexible scope of the neopharynx, barium
      swallows, 24-hour pH probes, and /or transnasal esophagoscopy (TNE). In 13 of 22
      patients who had voicing difficulties and no evidence of reflux on these tests,
      empiric treatment with antireflux medications had been documented. The 22
      patients were closely monitored to determine the role of reflux therapy and
      subsequent voicing outcomes. RESULTS: Of the 22 patients studied, 9 were noted to
      have granulation tissue on the tracheal side of the prosthesis. All nine patients
      had complete resolution of the granulation tissue after antireflux treatment, and
      seven of nine were able to voice again. Of the patients with no obvious reason
      for TEP failure who were empirically treated for reflux, 62% (8 of 13) had TEP
      voice after treatment. Seventy-seven percent of our patients (17 of 22) had a
      positive response to treatment with aggressive reflux therapy. CONCLUSIONS:
      Previous studies have demonstrated patients with a total laryngectomy and/or
      radiation therapy have increased reflux. This study addresses reflux as a
      potential cause of TEP voicing problems. We noted 41% (9 of 22) of patients with
      voicing difficulties had granulation tissue surrounding the prosthesis as a
      result of reflux. Aggressive antireflux therapy proved beneficial in eradicating
      this problem. Prophylactic antireflux therapy may be warranted for patients
      undergoing TEP to reduce voicing problems.

PMID- 19117291
TI  - EGFR expression in primary squamous cell carcinoma of the thyroid.
AB  - We present the case of a 57-year-old male with primary squamous cell carcinoma of
      the thyroid (PSCCT). Epidermal growth factor receptor (EGFR) staining was
      strongly positive. Pharmaceuticals targeting EGFR may provide an additional
      therapeutic option for this rare disease with extremely poor prognosis.

PMID- 19117292
TI  - Vacuum-assisted closure therapy in the management of head and neck wounds.
AB  - OBJECTIVES: The wound vacuum-assisted closure (VAC) has been used in many areas
      of surgery to promote healing and facilitate secondary reconstruction. Until
      recently, this treatment modality was overlooked in the otolaryngology
      literature, and the authors propose that its use should be routine in the
      treatment of complex head and neck wounds. STUDY DESIGN: An unbiased cohort study
      without conflict of interest at two tertiary care centers. MATERIALS AND METHODS:
      All patients treated by the authors presented with complex head and neck wounds
      from 2005 to 2007 and were subjected to wound VAC therapy. The wound VAC dressing
      was changed every 72 hours, and the wound etiology, wound site, history of
      chemotherapy and radiation, hospital duration, gender, outcome, and ancillary
      procedures were recorded. RESULTS: Nineteen patients with 33 wounds were treated
      using VAC therapy. Eighty-four percent of these patients healed completely
      without the need for further surgical intervention. The mean age of this cohort
      was 63.2 years, with a range of 48-75 years. Males far outnumbered females in
      this study (17:2). Outpatient therapy commenced at discharge after an average of
      11.4 days following a hospital stay ranging between 5 and 28 days. Adjunctive
      procedures performed during and after VAC therapy included hyperbaric oxygen
      treatment, dermal grafts, salivary diversion, and regional flap reconstruction.
      CONCLUSIONS: This study shows the applicability and versatility of vacuum
      assisted wound closure in the head and neck. Based on our results the authors
      feel that this mode of therapy should be a routine part of the Otolaryngologist's
      armamentarium for the treatment of complex and refractory head and neck wounds.

PMID- 19117293
TI  - The predictive and therapeutic value of thymidine phosphorylase and
      dihydropyrimidine dehydrogenase in capecitabine (Xeloda)-based chemotherapy for
      head and neck cancer.
AB  - OBJECTIVES: To evaluate whether two molecular biomarkers, thymidine phosphorylase
      (TP) and dihydropyrimidine dehydrogenase (DPD), could be clinically useful in
      predicting and improving the chemotherapeutic outcome of the oral
      fluoropyrimidine capecitabine (5'-DFUR or Xeloda), in the treatment of human head
      and neck squamous cell carcinoma (HNSCC). EXPERIMENTAL DESIGN: Quantitative
      reverse-transcriptase polymerase chain reaction was used to determine the TP and
      DPD expression levels in different HNSCC cell lines. The TP to DPD ratio was
      calculated and compared to the relative chemosensitivity between cell lines after
      treatment with 5'-DFUR. The effect of TP transgene expression to alter the TP to
      DPD ratio and hence optimize the therapeutic outcome of capecitabine treatment
      was further evaluated in a murine model of human HNSCC using immunohistochemistry
      to detect TP and DPD expression in vivo. RESULTS: No correlation was detected
      between sensitivity to 5'-DFUR and the relative expression levels of TP or DPD in
      the multiple HNSCC cell lines tested. However, significant correlation was
      observed between the TP to DPD ratio versus drug resistance of the HNSCC cells (r
      = -0.914, p = 0.0281). In addition, we demonstrate that transgene expression of
      TP significantly enhanced the tumoricidal effect of capecitabine in HNSCC tumors
      with otherwise low endogenous TP to DPD ratios. This antitumor effect was
      observed up to 30 days after treatment. CONCLUSIONS: The results of this study
      suggest that HNSCC patients who would most benefit from capecitabine-based
      chemotherapy could be identified by examining the TP to DPD ratio of their
      tumors. Furthermore, we demonstrate the potential role of TP gene therapy in TP
      to DPD ratio manipulation to optimize the tumoricidal effect of capecitabine.

PMID- 19117294
TI  - Regeneration of aged vocal fold: first human case treated with fibroblast growth
      factor.
AB  - BACKGROUND/OBJECTIVES: Aged vocal folds are characterized by atrophy of the
      mucosa, which caused dysphonia and is difficult to treat. We have revealed a
      therapeutic potential of basic fibroblast growth factor (bFGF) for tissue
      regeneration of the aged vocal fold. We report here the first human case that has
      been treated with bFGF. STUDY DESIGN: Institutional review board-approved
      clinical human trial. METHODS: A 63-year-old male with atrophied vocal folds was
      treated by local injection of 10 mug of bFGF into the left vocal fold under
      topical anesthesia. The effects of the injection were examined after 1 to 3
      months by videostroboscopy, acoustic, and aerodynamic measurements. RESULTS: The
      atrophy of the vocal fold was improved at 1 week after the injection, and glottic
      gap disappeared. Aerodynamic and acoustic parameters also showed remarkable
      improvement. These positive effects were maintained up to 3 months. CONCLUSIONS:
      The first case with aged vocal folds treated with bFGF administration was
      presented. The results are encouraging, suggesting therapeutic effects of bFGF
      for atrophied vocal folds in human.

PMID- 19117295
TI  - Genes involved in radiation therapy response in head and neck cancers.
AB  - OBJECTIVES: This is a pilot study designed to identify gene expression profiles
      able to stratify head and neck squamous cell carcinoma (HNSCC) tumors that may or
      may not respond to chemoradiation or radiation therapy. STUDY DESIGN: We
      prospectively evaluated 14 HNSCC specimens, arising from patients undergoing
      chemoradiotherapy or radiotherapy alone with curative intent. A complete response
      was assessed by clinical evaluation with no evidence of gross tumor after a 2
      year follow-up period. METHODS: Residual biopsy samples from eight complete
      responders (CR) and six nonresponders (NR) were evaluated by genome-wide gene
      expression profiling using HG-U133A 2.0 arrays. Univariate parametric t-tests
      with proportion of false discoveries controlled by multivariate permutation tests
      were used to identify genes with significantly different gene expression levels
      between CR and NR cases. Six different prediction algorithms were used to build
      gene predictor lists. Three representative genes showing 100% crossvalidation
      support after leave-one-out crossvalidation (LOOCV) were further validated using
      real-time QRT-PCR. RESULTS: We identified 167 significant probe sets that
      discriminate between the two classes, which were used to build gene predictor
      lists. Thus, 142 probe sets showed an accuracy of prediction ranging from 93% to
      100% across all six prediction algorithms. The genes represented by these 142
      probe sets were further classified into different functional networks that
      included cellular development, cellular movement, and cancer. CONCLUSIONS: The
      results presented herein offer encouraging preliminary data that may provide a
      basis for a more precise prognosis of HNSCC, as well as a molecular-based therapy
      decision for the management of these cancers.

PMID- 19117296
TI  - Iatrogenic esophageal submucosal dissection after attempted diagnostic
      gastroscopy (with videos).
AB  - Diagnostic esophagogastroduodenoscopy (EGD) is generally a very safe procedure.
      We report the first case of iatrogenic esophageal submucosal dissection after an
      attempted diagnostic gastroscopy in a patient with a small previously undiagnosed
      Zenker's diverticulum (ZD). After EGD, she developed severe dysphagia with the
      inability to swallow solids, liquids, and even her own saliva. On barium swallow
      study, there was a column of contrast below the upper esophageal sphincter, and
      this was misdiagnosed as a large ZD by the radiologist. The resultant stricture
      was successfully managed with endoscopic balloon dilatation under fluoroscopy
      with wire-guided cannulation. The ZD was treated with flexible endoscopic clip
      assisted diverticulotomy. Iatrogenic submucosal dissection is a unique
      complication of upper endoscopy. Endoscopists, otolaryngologists, radiologists,
      and cardiothoracic surgeons should be aware of this condition and prepare to
      manage it appropriately. If the patient is stable and the possibility of
      perforation is small, conservative and supportive care can be tried first. A
      surgical gastrostomy tube can be placed for enteral feeding. In patients with ZD,
      ZD recognition and gentle manipulation is strongly recommended during esophageal
      intubation.

PMID- 19117297
TI  - Transforming growth factor-beta1 shows an incremental osteoinductive dose
      response relationship.
AB  - OBJECTIVE: To determine if there is a dose-response curve for TGF-beta1 in a
      rabbit calvarial defect model. STUDY DESIGN: Controlled animal study using arms
      of increasing concentrations of TGF-beta1 to evaluate the osteoinductive
      potential of each arm. METHODS: Sixteen skeletally mature New Zealand white
      rabbits were randomized into control and experimental arms. Incremental doses of
      TGF-beta1 delivered in an inactivated guanidine-extracted demineralized bone
      matrix (Gu-DBM) carrier were implanted into a critically sized calvarial defect.
      The animals were sacrificed at 4 weeks and histomorphometric analysis was then
      accomplished. RESULTS: TGF-beta1 showed a dose-response relationship, with the
      higher doses chosen for this study causing more robust osteoinduction.
      CONCLUSIONS: In this pilot dosing study, TGF-beta1 demonstrates increasing
      osteoinduction with increasing dose levels in this animal model.

PMID- 19117298
TI  - Stellate cells in the human child vocal fold macula flava.
AB  - OBJECTIVES: Vitamin A-storing vocal fold stellate cells (SCs) in the macula flava
      (MF) are hypothesized to be involved in the metabolism of extracellular matrices
      (EM) of the human vocal fold mucosa (VFM). The SCs in the child VFM were
      examined. STUDY DESIGN: Histologic analysis of cadaveric human child VFM.
      METHODS: Light and electron microscopic investigations of SCs in the human child
      VFM were carried out on three excised human child larynges. RESULTS: The SCs were
      stellate and dense in the child MF. They had cytoplasmic processes, possessed
      lipid droplets, and stored vitamin A in their cytoplasm. The SCs had a small
      nucleus-cytoplasm ratio and rough endoplasmic reticula, suggesting constant
      protein synthesis in these cells. There were vesicles along the periphery of the
      cytoplasm, and newly released amorphous materials were seen on the cell surface.
      There were dense reticular, collagenous, and elastic fibers around SCs. The SCs
      exhibited strong cytoplasm staining with periodic acid-Schiff stain and type III
      collagen. Most of the VFSCs showed CD44 (a cell surface receptor for hyaluronic
      acid) expression, and a large amount of hyaluronic acid was present immediately
      adjacent to SCs. This study revealed several morphologic differences between the
      SCs in the MF and the conventional fibroblasts in the VFM. CONCLUSIONS: The SCs
      in the child MF constantly synthesized EM, essential for viscoelastic properties
      of the lamina propria of the human VFM, in the stage of vocal fold growth and
      development. The SCs in the MF were inferred to be involved in the growth and
      development of human VFM.

PMID- 19117299
TI  - Incidence and indications for revision cochlear implant surgery in adults and
      children.
AB  - OBJECTIVES/HYPOTHESIS: To identify the incidence of and common causes for
      cochlear implant revision. STUDY DESIGN: Retrospective case series. METHODS:
      Operative records were reviewed for all cases of revision cochlear implantation
      from 1992 to 2006. The causes for reimplantation were classified as hard device
      failure, soft device failure, exposure/infection, receiver/stimulator migration,
      and electrode migration. Manufacturers' failure analysis of explanted devices was
      likewise determined. RESULTS: Eight hundred and six cochlear implants were
      performed during the study period including 44 (5.5%) revision procedures. The
      revision rate was 7.3% for children and 3.8% for adults and reached statistical
      significant difference. The most common reasons for revision were device failure
      (78%; 55% hard failure, 23% soft failure) followed by electrode migration (9%)
      and receiver/stimulator migration (7%). Manufacturers' analysis of failed devices
      revealed loss of hermetic seal and cracked cases to be the most common causes of
      failure. Bench analysis of 5/10 explanted devices that were soft failures
      demonstrated identifiable device defects. CONCLUSIONS: Revision cochlear implant
      surgery is an infrequent occurrence. Its incidence appears to be higher in
      children than in adults, although in this series does not appear to be due to
      increased wound complications, infections, or trauma. Explanted implants that
      have soft failure as the etiology may have demonstrable defects on bench testing.

PMID- 19117300
TI  - Monitoring stress levels in postgraduate medical training.
AB  - OBJECTIVES: The Accreditation Council for Graduate Medical Education (ACGME)
      mandates that residency Program Directors (PD) monitor resident well-being,
      including stress. Burnout, as a measure of work-related stress, is defined by a
      high degree of emotional exhaustion and depersonalization, and a low degree of
      personal accomplishment using the Maslach Burnout Inventory-Human Services Survey
      (MBI-HSS). The purpose of this study is to describe the use of the MBI-HSS as a
      method of monitoring stress levels in an academic otolaryngology residency
      training program and introduce this survey as a tool for wider use in meeting
      ACGME requirements. METHODS: The MBI-HSS was administered to residents in an
      academic otolaryngology residency training program on three separate occasions:
      at the beginning, middle, and end of different academic years. In addition, at
      the time of the third administration, the MBI-HSS was completed by faculty and
      staff in the same department. Surveys were completed and collected anonymously.
      Responses were scored against normative data from the MBI-HSS overall sample and
      the medicine subscale. Low, average, and high levels of burnout were identified
      for the individual categories of emotional exhaustion (EE), depersonalization
      (DP), and personal accomplishment (PA); average levels for each category were
      calculated. RESULTS: Twenty-two residents completed the first survey, taken near
      the end of an academic year; 19 completed the second administration in the middle
      of the following academic year; and 24 completed the third survey at the
      beginning of the subsequent academic year. Thirteen faculty and 23 staff also
      completed the third survey. We found that three, one, and one residents reported
      high levels of burnout on the first, second, and third surveys, respectively.
      These figures compare to one faculty member and no staff members in the same
      department reporting high levels of burnout. CONCLUSIONS: The MBI-HSS is an
      established and validated tool for identifying burnout in resident physicians.
      Residency PDs may find the MBI-HSS useful as an aid in monitoring resident well
      being and stress. In our own department, we found levels of burnout comparable to
      those previously reported for residents and faculty in this specialty.

PMID- 19117301
TI  - An early detection protocol for invasive fungal sinusitis in neutropenic patients
      successfully reduces extent of disease at presentation and long term morbidity.
AB  - OBJECTIVES: To evaluate a multidisciplinary early intervention protocol for
      invasive fungal sinusitis (IFS) in neutropenic patients and its effect on degree
      of tissue involvement at time of presentation and effect on morbidity and
      mortality. STUDY DESIGN: Retrospective review. METHODS: A chart review was
      performed for cases of acute fulminant IFS in neutropenic patients at Emory
      University Hospital from 1995 to 2007. Inclusion required tissue diagnosis of
      IFS, neutropenia, and adequate records of the following: tissue involvement at
      presentation, number and extent of surgical procedures performed, morbidity, and
      mortality. Group 1 included patients prior to 2001, and group 2 included patients
      after protocol initiation in 2001. The groups were compared for the number of
      tissue sites involved at presentation, number of surgical procedures performed,
      long-term morbidity, and mortality. RESULTS: Twenty-eight cases of IFS were
      identified. The average number of sites involved at presentation was 2.5 in group
      1 and 1.5 in group 2 (P = .059). The average number of procedures was 2.2 in
      group 1 and 1.0 in group 2 (P = .026). Long-term morbidity occurred in 43% (6/14)
      of group 1 patients compared with 7.1% (1/14) of group 2 patients (P = .029).
      Mortality from IFS was 7.1% in group 1 and 7.1% in group 2. CONCLUSIONS: IFS
      requires early diagnosis and treatment for optimum outcome. A protocol of early
      intervention for neutropenic patients is effective in early detection of IFS with
      fewer sites of involvement at diagnosis, fewer surgeries, and less long-term
      morbidity. No difference in survival was found, as this is more a factor of the
      underlying cause of the neutropenia.

PMID- 19117302
TI  - Modeling flow in a compromised pediatric airway breathing air and heliox.
AB  - OBJECTIVES/HYPOTHESIS: The aim of this study was to perform computer simulations
      of flow within an accurate model of a pediatric airway with subglottic stenosis.
      It is believed that the airflow characteristics in a stenotic airway are strongly
      related to the sensation of dyspnea. METHODS: Computed tomography images through
      the respiratory tract of an infant with subglottic stenosis were used to
      construct the three-dimensional geometry of the airway. By using computational
      fluid dynamics (CFD) modeling to capture airway flow patterns during inspiration
      and expiration, we obtained information pertaining to flow velocity, static
      airway wall pressure, pressure drop across the stenosis, and wall shear stress.
      These simulations were performed with both air and heliox (helium-oxygen
      mixture). RESULTS: Unlike air, heliox maintained laminar flow through the
      stenosis. The calculated pressure drop over stenosis was lower for the heliox
      flow in contrast to the airflow case. This led to an approximately 40% decrease
      in airway resistance when using heliox and presumably causes a decrease in the
      level of effort required for breathing. CONCLUSIONS: CFD simulations offer a
      quantitative method of evaluating airway flow dynamics in patients with airway
      abnormalities. CFD modeling illustrated the flow features and quantified flow
      parameters within a pediatric airway with subglottic stenosis. Simulations with
      air and heliox conditions mirrored the known clinical benefits of heliox compared
      with air. We anticipate that computer simulation models will ultimately allow a
      better understanding of changes in flow caused by specific medical and surgical
      interventions in patients with conditions associated with dyspnea.

PMID- 19117303
TI  - Predictability of cochlear implant outcome in families.
AB  - OBJECTIVES: The purpose of this study is to determine if the performance of the
      first implanted member of a family predicts the performance of subsequently
      implanted family members. STUDY DESIGN: Retrospective chart review. METHODS:
      Seventy-one cochlear implant recipients, each belonging to a family with two or
      more implanted members, were the subjects of this study. Routine audiometric
      measurements and age-appropriate speech perception tests were performed pre- and
      postoperatively. In addition, length of deafness, age at implantation, etiology,
      and length of device usage were correlated to outcome. RESULTS: All implant
      recipients within a family showed improvement postimplantation, and the
      predictive component between family members was strong. Presence of GJB2
      mutations and greater age at implantation were predictive of poorer
      rehabilitative outcome, while length of device usage was associated with improved
      speech perception scores. CONCLUSIONS: On average, if the first implanted family
      member performs well with a cochlear implant, those following will do well;
      however, GJB2-related deafness and increased age at implantation are associated
      with poorer outcome. These findings have important implications for members of
      families considering cochlear implantation.

PMID- 19117304
TI  - Tonsillectomy vs. deep tonsil biopsies in detecting occult tonsil tumors.
AB  - OBJECTIVES: To compare the yield of detecting occult tumors by performing
      tonsillectomy and deep tonsil biopsies in patients with metastatic carcinoma to
      the neck in whom a primary tumor was not evident on physical examination,
      radiography, or panendoscopy. STUDY DESIGN: Retrospective study. METHODS: Over a
      10-year period, the charts of all patients diagnosed with metastatic carcinoma to
      the neck in whom a primary tumor was not evident on examination, imaging, and
      panendoscopy were reviewed. Specifically, we compared groups of patients who had
      undergone diagnostic tonsillectomy with those who had undergone deep tonsil
      biopsies in search of an occult primary tumor. RESULTS: One hundred twenty-two
      patients were identified as meeting study criteria. All underwent directed
      biopsies of the tongue base, hypopharynx, and nasopharynx as well as either deep
      tonsil biopsies or diagnostic tonsillectomy. Deep tonsil biopsies were performed
      in 95 patients. In this group, 11 primary tumors were subsequently identified
      (11.6%): three in the tonsil, six in the tongue base, one in the hypopharynx, and
      one in the nasopharynx. Tonsillectomy was performed in 27 patients. Eleven
      primary tumors were identified (40.7%): eight in the tonsils, two in the tongue
      base, and one in the hypopharynx. All tonsil primary tumors identified were
      ipsilateral to the presenting neck mass. The overall yield of finding an occult
      primary carcinoma in the tonsil was 3.2% for deep tonsil biopsies vs. 29.6% for
      tonsillectomies (P < .0002). CONCLUSIONS: Tonsillectomy offers a significantly
      higher likelihood of finding occult tonsillar tumors than deep tonsil biopsy.

PMID- 19117305
TI  - Role of vortices in voice production: normal versus asymmetric tension.
AB  - OBJECTIVES: Decreasing the closing speed of the vocal folds can reduce loudness
      and energy in the higher frequency harmonics, resulting in reduced voice quality.
      Our aim was to study the correlation between higher frequencies and the
      intraglottal vorticity (which contributes to rapid closing by producing transient
      negative intraglottal pressures). METHODS: Using six excised canine larynges
      (three with symmetric and three with asymmetric, periodic vocal fold motion),
      intraglottal vorticity was calculated from 2D velocity fields measured using
      particle imaging velocimetry. RESULTS: There is a strong correlation between
      intraglottal vorticity and acoustic energy in the higher frequencies; in periodic
      asymmetric motion, the vorticity and higher frequencies are both reduced.
      CONCLUSIONS: For unilateral vocal fold paralysis, these findings suggest one
      reason why periodic, asymmetric motion, may produce an abnormal voice. Further
      study will help determine when and why reinnervation, as opposed to
      medialization, may result in better voice quality.

PMID- 19117306
TI  - Endoscopic endonasal surgery for petrous apex lesions.
AB  - BACKGROUND: Endoscopic endonasal approaches to the ventral skull base are
      categorized based on their orientation in coronal and sagittal planes. For all of
      these approaches, the sphenoid sinus is the starting point, and provides
      orientation to important vascular and neural structures. Surgical approaches to
      the petrous apex include 1) a medial approach, 2) a medial approach with internal
      carotid artery (ICA) lateralization, and 3) a transpterygoid infrapetrous
      approach (inferior to the petrous internal carotid artery). The choice of a
      surgical approach depends on the relationship of the lesion to the internal
      carotid artery (medial or inferior), degree of medial expansion, and pathology.
      The purpose of this paper is to discuss the anatomic and technical features of
      endoscopic surgical approaches to the petrous apex, provide a new classification
      for approaches that focuses on the relationship of the lesion to the petrous
      internal carotid artery, and provide outcomes data on our first 20 endoscopic
      petrous apex approaches. METHODS: A retrospective clinical outcome study of
      endoscopic petrous apex surgeries was performed at the University of Pittsburgh
      Medical Center. The medical records from patients with endoscopic endonasal
      approaches to isolated petrous apex lesions were reviewed for demographics,
      diagnoses, presentation, endoscopic approach, and clinical outcomes. Patients
      with lesions that extended into the petrous apex but were not isolated to the
      petrous apex were excluded (e.g., clival chordoma with extension into the petrous
      apex). RESULTS: Twenty patients were included in the analysis: 13 inflammatory
      cystic lesions (9 cholesterol granulomas and four petrous apicitis) and 7 solid
      lesions. Chondrosarcoma was the most common solid petrous apex lesion in our
      series. Twelve of 13 cystic lesions were drained endoscopically (one surgery was
      aborted early in the series). All drained patients had resolution of presenting
      symptoms. One patient had closure of the outflow tract without return of symptoms
      and one patient had revision endoscopic drainage due to scarring and neo
      osteogenesis and return of unilateral headache. No carotid injuries and no new
      cranial neuropathies occurred perioperatively. The advantages and limitations of
      the medial transsphenoidal approaches (with and without carotid mobilization) and
      the transpterygoid infrapetrous approach are discussed. CONCLUSIONS: The
      endoscopic endonasal approach to petrous apex lesions is safe and effective for
      appropriately selected patients in the hands of experienced endoscopic skull base
      surgeons. If offers advantages of removing the hearing and facial nerve risks
      from the transtemporal/transcranial approaches and allows for a larger and more
      natural drainage pathway into the sinuses.

PMID- 19117307
TI  - Destructive otomastoiditis by MRSA from porcine origin.
AB  - A 63-year-old female pig farmer was referred to our department with a protracted
      course of otomastoiditis with destruction of the tympanic roof and cerebrospinal
      fluid leakage. The patient underwent a cortical mastoidectomy with closure of a
      large dural defect. Cultures of the middle ear effusion yielded a methicillin
      resistant Staphylococcus aureus (MRSA), which upon further analysis was found to
      be from porcine origin. To our knowledge, this is the first report of a
      complicated case of otomastoiditis caused by a pig-type MRSA.

PMID- 19117308
TI  - Control of vocal fold cover stiffness by laryngeal muscles: a preliminary study.
AB  - OBJECTIVES: To perform preliminary measurements of the shear modulus of the vocal
      fold cover layer during intrinsic laryngeal muscle contraction. STUDY DESIGN:
      Shear modulus was measured in an in vivo canine larynx and an ex vivo human
      larynx. METHODS: Shear stress was applied to the transverse axis of the vocal
      fold using a modified linear skin rheometer (LSR) via an attached suction probe.
      The probe displacement in response to the applied force was measured at various
      levels of laryngeal muscle contraction. The force-displacement data were used to
      derive the shear modulus using a simple shear model. In the ex vivo human larynx,
      lateral cricoarytenoid (LCA) muscle and cricothyroid (CT) muscle activity was
      simulated with arytenoid adduction and cricothyroid approximation sutures,
      respectively. In the in vivo canine, adductor muscle and CT muscle contraction
      was induced with graded stimulation of the recurrent laryngeal nerve (RLN) and
      the superior laryngeal nerves (SLN), respectively. RESULTS: : Baseline shear
      modulus was between 1,076 and 1,307 Pascals. In the ex vivo human larynx, the
      shear modulus increased gradually to a maximum of 1.6 times baseline value with
      graded arytenoid adduction and 3.7 times baseline value with cricothyroid
      approximation. In the in vivo larynx, the shear modulus increased to a maximum of
      1.6 times baseline value with RLN stimulation and 2.5 times baseline value with
      SLN stimulation. CONCLUSIONS: Findings are in agreement with the cover-body model
      in that cricothyroid muscle activity generates a greater change in cover
      stiffness than laryngeal adductors. The role of the individual laryngeal
      adductors (thyroarytenoid [TA] vs. LCA) in control of vocal fold cover stiffness
      remains to be further elucidated.

PMID- 19117309
TI  - Endoscopic CO2 laser cricopharyngeal myotomy.
AB  - OBJECTIVES: Over the past 10 years, endoscopic cricopharyngeal myotomy laser
      surgery has been proposed as an alternative to transcervical cricopharyngeal
      myotomy. We will describe the technique and review the literature so that it may
      gain credence as a viable option for the treatment of cricopharyngeal achalasia.
      METHODS: A literature review of endoscopic and transcervical cricopharyngeal
      myotomy will be performed. The technical aspects of endoscopic cricopharyngeal
      myotomy will be presented and accompanied by intraoperative photographs,
      illustrations, and an online video demonstration. RESULTS: Endoscopic
      cricopharyngeal myotomy is a well-tolerated procedure with low morbidity and good
      outcomes. It can be performed by surgeons who are comfortable with transoral
      laryngopharyngeal laser surgery. CONCLUSIONS: Endoscopic cricopharyngeal myotomy
      is a viable alternative to classic transcervical cricopharyngeal myotomy with
      equivalent outcomes and comparable if not less morbidity.

PMID- 19117310
TI  - The health and resource utilization of Canadians with chronic rhinosinusitis.
AB  - OBJECTIVES: To determine the impact of chronic rhinosinusitis (CRS) on the
      physical and mental health and health-resource utilization of Canadians. STUDY
      DESIGN: Cross-sectional. METHODS: Data from the detailed health portion of cycle
      3 (1998-1999) of the National Population Health Survey (NPHS), which involved
      17,000 Canadians, were used to evaluate Canadians with self-reported CRS.
      RESULTS: NPHS data confirmed lower mental and physical health, with CRS sufferers
      being almost three times more likely to report their health as poor (4.6% vs.
      1.7%). Health Utility Index data identified a significant decline in the mental
      health of patients with CRS, which was associated with more depression (8.4% vs.
      4.1%), more antidepressant use (9.1% vs. 4.6%), and more visits to mental-health
      professionals (11.8% vs. 7.0%). CONCLUSIONS: CRS significantly affects both
      physical and mental health. The mental impact of CRS remains largely unrecognized
      and should be of greater focus during patient care and in further research.

PMID- 19117311
TI  - Application of the Vibrant Soundbridge to unilateral osseous atresia cases.
AB  - OBJECTIVES/HYPOTHESIS: Patients with high-grade atresia-microtia suffer from a
      combined malformation of the outer and middle ears, typically leading to a severe
      hearing impairment. Long-term results of middle ear reconstruction with
      tympanoplasty are often insufficient due to persistent air-bone gaps, and new
      techniques in hearing rehabilitation are required. The objective of this research
      is to evaluate the active middle ear implant, the Vibrant Soundbridge (VSB), for
      hearing rehabilitation of patients with unilateral osseous aural atresia. STUDY
      DESIGN: Prospective analysis of a consecutive cohort of seven atresia patients
      (mean age = 15 years). METHODS: During plastic auricular reconstruction of
      unilateral atresia-microtia cases, an access through the bony atresia plate was
      drilled. The floating mass transducer was coupled to the stapes (or remaining
      stapes suprastructure), ossicular chain, or round window, depending on the
      anatomic needs of the patient. Audiometric testing, including pure-tone
      thresholds, and speech testing in quiet and noise were performed. RESULTS: : The
      mean threshold with the VSB activated in the free field warble tone audiometry
      was 23.8 dB hearing level (HL). Mean functional gain was 45.5 dB HL. Mean aided
      free field speech discrimination in quiet was 64% at 50 dB, 99% at 65 dB, and
      100% at 80 dB. CONCLUSIONS: By circumventing the malformed middle ear and
      directly stimulating the cochlea, the VSB provides a new rehabilitation option
      for atresia patients. We conclude that the procedure is safe and effective and
      can be implemented in combination with outer ear reconstruction.

PMID- 19117312
TI  - Maxillary mucosal cyst is not a manifestation of rhinosinusitis: results of a
      prospective three-dimensional CT study of ophthalmic patients.
AB  - BACKGROUND: Mucosal cysts in the maxillary antrum (MMC) are a common finding in
      imaging of the paranasal sinuses. Their significance remains in doubt and their
      prevalence in the general nonrhinitic population is unknown. OBJECTIVES: To
      establish the prevalence of MMCs in patients without nasal complaints and
      identify any association with putative causative factors. To identify any
      correlation between objective radiologic evidence of chronic rhinosinusitis or
      dental disease and the presence of cysts. STUDY DESIGN: Prospective case series.
      METHODS: Computed tomography (CT) images from 257 patients undergoing scans of
      the orbits for ophthalmic reasons were entered into this study. Patients
      responded to a questionnaire prior to scanning inquiring about nasal complaints,
      treatment for nasal disorders, previous nasal injury, allergy, asthma, recent
      upper respiratory tract infection, and dental root disease of the upper jaw.
      RESULTS: Overall 35.6% of patients studied had radiologic evidence of at least
      one maxillary mucosal cyst. There was no association between the presence of
      cysts and subjective or objective evidence of sinus or dental disease.
      Specifically, there was no correlation between the presence of cysts and the
      total and ostiomeatal complex Lund-Mackay radiologic scores. CONCLUSIONS:
      Maxillary mucosal cysts are prevalent in nonrhinitic patients and do not reflect
      sinus or dental disease. Their presence should not be an indication for sinus
      surgery.

PMID- 19117314
TI  - Long-term outcomes of intraoral submandibular stone removal in children as
      compared with adults.
AB  - OBJECTIVES: To investigate the long-term outcomes of intraoral submandibular
      stone removal in children as compared with those in adult patients. STUDY DESIGN:
      Retrospective clinical review. METHODS: We retrospectively analyzed the medical
      records of 17 children and 48 adult patients who had undergone intraoral stone
      removal for submandibular sialolithiasis and followed up for more than 24 months.
      The mean durations of follow-up were 43.4 months and 49.4 months for children and
      adults, respectively. The long-term outcomes were compared between the two age
      groups. RESULTS: Intraoral submandibular stone removal achieved the status of
      "symptom-free" in 82.4% of child and 83.3% of adult patients. Recurrence in the
      affected gland was not found in any children but was found in two adult patients
      (4.2%). In pediatric patients with calculi around the hilum, a higher incidence
      (50%) of having long-term complaints was noted as compared with cases with
      calculi in the proximal and distal duct (P = .029). However, this difference was
      not evident in adult patients. CONCLUSIONS: Intraoral removal of submandibular
      stones is an effective treatment option with an acceptable long-term outcome for
      children. Nevertheless, in cases with calculi around the hilum, a careful
      surgical approach is required.

PMID- 19117313
TI  - EMLA Cream coated on the rigid bronchoscope for tracheobronchial foreign body
      removal in children.
AB  - OBJECTIVES: Removal of a tracheal or bronchial foreign body is a common emergent
      surgical procedure in children. The anesthetic management can be challenging.
      EMLA Cream (EC) has been widely used to provide topical anesthesia. In the
      present study, we evaluate the efficacy and safety of EC coated on the rigid
      bronchoscope for tracheobronchial foreign body removal in children undergoing
      intravenous anesthesia with spontaneous ventilation. STUDY DESIGN: The authors
      conducted a randomized, double-blind, placebo-controlled clinical trial. METHODS:
      Thirty patients were randomized to receive either EC or placebo (lubricant
      ointment) coated on the rigid bronchoscope. Intravenous anesthesia and
      spontaneous ventilation were performed in all patients. Heart rate, blood
      pressure, pulse oxygen saturation (SpO(2)) and frequency and degree of breath
      holding were recorded. After surgery, the bronchoscopist rated overall surgical
      manipulation as excellent, fair, and poor. The durations of postoperative care
      were also recorded. RESULTS: Episodes of oxygen desaturation (SpO(2) < 90%)
      occurred in 3/15 (20%) patients in the EC group and in 9/15 (60%) patients in the
      control group (P < .05). Occurrences and degrees of breath holding were less in
      the EC group than that in the control group (P < .05). Ranks of surgical
      manipulation were excellent in 80% of patients in the EC group versus 13% of
      patients in the control group (P < .05). The durations of postoperative care were
      shorter in the EC group than that in the control group (P < .05). CONCLUSIONS: EC
      coated on the rigid bronchoscope combined with intravenous anesthesia could
      provide more efficacious and safer anesthesia for tracheobronchial foreign body
      removal in children under spontaneous ventilation.

PMID- 19117315
TI  - Susac's syndrome: intratympanic therapy for hearing loss and a review of the
      literature.
AB  - Two cases of Susac's Syndrome are presented with a discussion of treatment
      modalities for the associated severe sensorineural deafness. Patients were
      managed with high dose oral steroids, anticoagulants and immunosuppressive drugs.
      The addition of intratympanic methylprednisolone injections were added to one
      patient's regimen with initial improvement but subsequent relapse and progression
      to profound deafness. The management of Susac's syndrome is difficult and still
      in need of innovative methods as the standard treatment continues to be
      ineffective in the long term.

PMID- 19117317
TI  - Lingual abscess from a grill cleaning brush bristle.
AB  - OBJECTIVES: 1) Describe the clinical presentation of a lingual abscess secondary
      to a foreign body. 2) Discuss the workup of glossopharyngeal neuralgia (GN). 3)
      Review existing literature. METHODS: Illustrative case report and literature
      review generated by PubMed citation search. RESULTS: This is a report of a
      patient who presented with severe tongue and ear pain, initially diagnosed with
      glossopharyngeal neuralgia. He subsequently returned with acute neck swelling,
      altered mental status, and rapidly progressive airway edema. After securing his
      airway, radiographic imaging confirmed a lingual abscess with a linear foreign
      body. He was taken emergently to the operating room for neck exploration with
      incision and drainage of the abscess. Despite inability to locate the foreign
      body, he had complete resolution of the abscess and airway edema. Subsequent CT
      scanning confirms the continued presence of the foreign body consistent with a
      grill cleaning brush bristle. DISCUSSION: Lingual abscesses are extremely
      uncommon. Diagnosis may be difficult and as a consequence, when they occur, they
      may result in airway compromise or sepsis. Major textbooks often omit description
      of this entity, which has been associated with oral trauma and with retained
      foreign bodies such as fish bones. This is the first case report of a near fatal
      lingual abscess due to a bristle from a grill cleaning brush. CONCLUSIONS: To
      date, there has been no published literature describing the development of a
      lingual abscess secondary to a bristle from a grill cleaning brush. We describe
      the presentation and management of this condition and how it may mimic
      glossopharyngeal neuralgia.

PMID- 19117316
TI  - Efficacy and safety of OK-432 immunotherapy of lymphatic malformations.
AB  - OBJECTIVES: To determine the efficacy and safety of the immunostimulant OK-432
      (Picibanil) as a treatment option in the management of children with
      cervicofacial lymphatic malformations. STUDY DESIGN: A prospective, randomized,
      multi-institutional phase II clinical trial at 27 U.S. academic medical centers.
      METHODS: 182 patients with lymphatic malformations (LM) were enrolled between
      January 1998 and November 2004. Of the 151 patients with complete case report
      forms, 117 patients were randomized into immediate or delayed treatment groups;
      34 patients were nonrandomized and assigned to the open-label group. Treatment
      consisted of a four-dose intralesional injection series of OK-432 at eight-week
      intervals. Patients randomized into the delayed treatment group served as
      observational controls for spontaneous regression. Response to therapy was
      measured radiographically by quantitating change in lesion size and graded as
      complete (90%-100%), substantial (60%-89%), intermediate (20%-59%), or none
      (<20%). RESULTS: Of 117 patients randomized with intent-to-treat, 68%
      demonstrated a complete or substantial response to OK-432 immunotherapy. Response
      data for macrocystic LM were higher, with a complete or substantial response in
      94% of patients; 63% of patients with mixed macrocystic-microcystic LM responded
      to treatment; no patients with microcystic LM responded to treatment. Spontaneous
      resolution occurred in less than 2% of patients. Median follow-up of 2.9 years
      demonstrated a 9% recurrence rate. Major adverse effects related to therapy
      occurred in 11 patients. As compared to historical surgical data on LM, OK-432
      immunotherapy is more effective (P < .001) and has a lower morbidity (P < .001).
      CONCLUSIONS: OK-432 immunotherapy is an effective, safe, and simple treatment
      option for the management of macrocystic cervicofacial LM. TRIAL REGISTRATION:
      ClinicalTrials.gov Identifier: NCT00010452.

PMID- 19117318
TI  - Glossopharyngeal schwannomas: a 100 year review.
AB  - OBJECTIVES: To review the literature on glossopharyngeal schwannomas with a focus
      on clinical presentation, radiologic/audiologic characteristics, and management
      options, and to propose a mechanism explaining the nature of vestibulocochlear
      dysfunction seen with these tumors. STUDY DESIGN: Contemporary review. METHODS:
      English literature search for cases of primary isolated glossopharyngeal
      schwannomas and chart review of two new cases. RESULTS: A total of 42
      glossopharyngeal schwannoma cases between 1908-2008 were reviewed. Of these 84%
      presented with vestibulocochlear symptoms whereas only 30% presented with
      glossopharyngeal symptoms. Tumors can occur anywhere along the CNIX; however, the
      majority of symptomatic cases are intracranial/intraosseous, which present with
      vestibulocochlear dysfunction. Reviewed cases typically described the caliber of
      CNVII and VIII on CT/MRI as normal. We present a case where notching and
      displacement of CNVIII by the tumor can be appreciated on MRI, allowing for the
      first correlation between clinical symptoms and imaging findings. Mid frequency
      SNHL was prevalent in contrast to the high-frequency pattern typical of
      vestibular schwannomas. Tonotopic studies of CNVIII mapped low-to-mid frequency
      fibers along the posterior medial surface corresponding to the area of greatest
      compression by glossopharyngeal schwannomas. CONCLUSION: Glossopharyngeal
      schwannomas usually present with vestibulocochlear rather than glossopharyngeal
      symptoms, likely due to CNVIII compression and displacement by tumor, which can
      be better appreciated with modern imaging. The tumor's location posterior and
      medial to CNVIII combined with the complex CNVIII tonotopic organization may
      account for the preferential mid-frequency hearing loss seen in these patients.

PMID- 19117319
TI  - IgE response to staphylococcal enterotoxins in adenoid tissues from atopic
      children.
AB  - OBJECTIVES/HYPOTHESIS: To evaluate local production of staphylococcal
      superantigen (SAg)-specific IgE in adenoid tissue and to compare its prevalence
      with that in the tonsil and serum, as well as its relationship with markers of
      allergic inflammation within adenoid tissue. STUDY DESIGN: Prospective randomized
      study. METHODS: We recruited 18 atopic children who had rhinitis symptoms and
      were sensitized to more than one common aeroallergen, and 22 nonatopic children
      undergoing adenotonsillectomy. Immunoassays were performed using adenoid tissue
      homogenate to quantify the levels of three staphylococcal SAg-specific IgE (SEA,
      SEB, and TSST-1), total IgE, eosinophil cationic protein (ECP), mast cell
      tryptase, and soluble CD23. RESULTS: Three kinds of SAg-specific IgE were
      detected in the adenoid and tonsil tissues of atopic patients, but not in those
      of nonatopic patients. In atopic children, the prevalence of SEA-, SEB-, and TSST
      1-specific IgE in adenoid tissues (61.1%, 27.8%, 33.3%, respectively) were higher
      than those in tonsil tissues (38.9%, 5.6%, 11.1%, respectively) and in sera
      (11.1%, 27.8%, 16.7%, respectively). Subjects with high SEA levels showed
      significantly higher serum and adenoid total IgE, with higher eosinophilia.
      Significant correlations were noted between SAg-specific IgE levels and tryptase
      levels in adenoid tissue. CONCLUSIONS: Local specific IgE response to
      staphylococcal SAgs, especially SEA may contribute to ongoing allergic
      inflammation in adenoid tissue from atopic children.

PMID- 19117320
TI  - Level of physical activity and characteristics associated with change following
      breast cancer diagnosis and treatment.
AB  - OBJECTIVE: While the physical and psychosocial benefits of participating in
      physical activity (PA) during and following breast cancer treatment are well
      understood, less is known about rates and uptake of PA following diagnosis. This
      paper explores the levels and patterns of PA among women recently diagnosed with
      breast cancer and the factors associated with change in activity levels. METHODS:
      Using a population-based recruitment approach, PA levels of 287 breast cancer
      patients were assessed at 6, 12 and 18 months post-diagnosis using the Behavioral
      Risk Factor Surveillance System, and then converted to MET (metabolic equivalent
      task)-hours/week. Regression analyses were used to explore the correlates
      associated with change between 6 and 18 months post-diagnosis. RESULTS: Although
      more than 80% of women participated in PA at each testing phases, more than 50%
      were considered insufficiently active or sedentary according to national
      recommendations and less than one-third reported engagement in vigorous or
      strength activities. Mean change in total MET-hours/week between 6 and 18 months
      post-diagnosis was minor (mean=0.10, median=0.0), however individual changes were
      substantial (ranging from -100 to +174 MET-hours/week). Results are more
      encouraging for the lower threshold of 3+ MET-hours/week, which may be most
      relevant specifically for breast cancer outcomes. CONCLUSIONS: Since the majority
      of women report insufficient levels of PA, there is a clear need for exercise
      interventions during and following breast cancer treatment. Few characteristics
      predict declines or improvements in PA levels, hence for optimal benefit,
      interventions should target the entire breast cancer population.

PMID- 19117321
TI  - Insights into prevention of human neural tube defects by folic acid arising from
      consideration of mouse mutants.
AB  - Almost 30 years after the initial study by Richard W. Smithells and coworkers, it
      is still unknown how maternal periconceptional folic acid supplementation
      prevents human neural tube defects (NTDs). In this article, questions about human
      NTD prevention are considered in relation to three groups of mouse models: NTD
      mutants that respond to folate, NTD mutants and strains that do not respond to
      folate, and mutants involving folate-pathway genes. Of the 200 mouse NTD mutants,
      only a few have been tested with folate; half respond and half do not. Among
      responsive mutants, folic acid supplementation reduces exencephaly and/or spina
      bifida aperta frequency in the Sp(2H), Sp, Cd, Cited2, Cart1, and Gcn5 mutants.
      Prevention ranges from 35 to 85%. The responsive Sp(2H) (Pax3) mutant has
      abnormal folate metabolism, but the responsive Cited2 mutant does not. Neither
      folic nor folinic acid reduces NTD frequency in Axd, Grhl3, Fkbp8, Map3k4, or Nog
      mutants or in the curly tail or SELH/Bc strains. Spina bifida frequency is
      reduced in Axd by methionine and in curly tail by inositol. Exencephaly frequency
      is reduced in SELH/Bc by an alternative commercial ration. Mutations in folate
      pathway genes do not cause NTDs, except for 30% exencephaly in folate-treated
      Folr1. Among folate-pathway mutants, neural tube closure is normal in Cbs, Folr2,
      Mthfd1, Mthfd2, Mthfr, and Shmt1 mutants. Embryos die by midgestation in Folr1,
      Mtr, Mtrr, and RFC1 mutants. The mouse models point to genetic heterogeneity in
      the ability to respond to folic acid and also to heterogeneity in genetic cause
      of NTDs that can be prevented by folic acid.

PMID- 19117326
TI  - Neurosonography to detect brain injury in a surviving monochorionic twin after
      demise of its co-twin.

PMID- 19117328
TI  - A randomized control trial of a supervised versus a self-directed exercise
      program for allogeneic stem cell transplant patients.
AB  - OBJECTIVES: To determine if therapist supervision of an exercise program produced
      better functional outcomes in allogeneic stem cell transplant patients than a
      patient-directed exercise program. METHODS: Sixty-one patients who were less than
      6 months post allogeneic stem cell transplant were randomly assigned to either a
      therapist supervised training group (supervised) or a patient-directed training
      group (Self-directed). Training consisted of aerobic exercises (treadmill,
      bicycle ergometer versus walking) and resistance exercises (free weights, weight
      machines versus resistive band activities). Subjects completed physical
      performance tests (50-foot fast walk, 6-min walk, forward reach, repeated sit-to
      stand, uniped stance) and the Brief Fatigue Inventory (BFI) before and after 4
      weeks of training. Pre- and post-training outcomes and group differences were
      analyzed by a Student t-test. RESULTS: Patients in both groups were similarly
      deconditioned at baseline. Training increased the 6-min walk distance and 50-foot
      walk in the supervised group by 12 and 14%, respectively, and increased the 6-min
      walk distance by 10% in the Self-directed group (p<0.05). BFI score for worst
      level of fatigue declined in both groups but not significantly. CONCLUSIONS:
      These results demonstrate that allogeneic transplant patients derive functional
      benefits from short-term exercise training regardless of how the training program
      is supervised. Determining (1) the reasons for the low participation rate (28%),
      (2) the patient-preferred characteristics of each exercise supervision style and
      (3) how best to match patient preference to exercise supervision style remain
      significant issues in this area of patient delivery services.

PMID- 19117329
TI  - Reach out to ENhancE Wellness in Older Cancer Survivors (RENEW): design, methods
      and recruitment challenges of a home-based exercise and diet intervention to
      improve physical function among long-term survivors of breast, prostate, and
      colorectal cancer.
AB  - OBJECTIVE: Cure rates for cancer are increasing, especially for breast, prostate,
      and colorectal cancer. Despite positive trends in survivorship, a cancer
      diagnosis can trigger accelerated functional decline that can threaten
      independence, reduce quality-of-life and increase healthcare costs, especially
      among the elderly who comprise the majority of survivors. Lifestyle interventions
      may hold promise in reorienting functional decline in older cancer survivors, but
      few studies have been conducted. METHODS: We describe the design and methods of a
      randomized controlled trial, RENEW (Reach out to ENhancE Wellness), that tests
      whether a home-based multi-behavior intervention focused on exercise, and
      including a low saturated fat, plant-based diet, would improve physical
      functioning among 641 older, long-term (>or=5 years post-diagnosis) survivors of
      breast, prostate, or colorectal cancer. Challenges to recruitment are examined.
      RESULTS: Twenty thousand and fifteen cases were approached, and screened using a
      two-step screening process to assure eligibility. This population of long-term,
      elderly cancer survivors had lower rates of response (approximately 11%) and
      higher rates of ineligibility (approximately 70%) than our previous intervention
      studies conducted on adults with newly diagnosed cancer. Significantly higher
      response rates were noted among survivors who were White, younger, and more
      proximal to diagnosis and breast cancer survivors (p-values<0.001). CONCLUSION:
      Older cancer survivors represent a vulnerable population for whom lifestyle
      interventions may hold promise. RENEW may provide guidance in allocating limited
      resources in order to maximize recruitment efforts aimed at this needy, but hard
      to-reach population.

PMID- 19117330
TI  - Ginger's (Zingiber officinale Roscoe) inhibition of rat colonic adenocarcinoma
      cells proliferation and angiogenesis in vitro.
AB  - Ginger's (Zingiber officinale Roscoe) natural bioactives, specifically ginger
      extract and 6-gingerol, were measured for their in vitro inhibition of two key
      aspects of colon cancer biology--cancer cell proliferation and angiogenic
      potential of endothelial cell tubule formation. Ginger extract was obtained via
      column distillation, while the 6-gingerol was purchased from Calbiochem.
      Antiproliferation activity was assessed through tritiated thymidine ([(3)H]Tdr)
      incorporation studies of YYT colon cancer cells; the anti-angiogenic ability of
      gingerol was assessed by a Matrigel assays using MS1 endothelial cells. These
      selected ginger bioactives had: 1) a direct effect on YYT rat cancer cell
      proliferation (6-1.5% ginger extract; 100-4 microM 6-gingerol); 2) an indirect
      effect on MS1 endothelial cell function either at the level of endothelial cell
      proliferation or through inhibition of MS1 endothelial cell tube formation (100
      0.8 microM). Compound 6-gingerol was most effective at lower doses in inhibiting
      endothelial cell tube formation. These in vitro studies show that 6-gingerol has
      two types of antitumor effects: 1) direct colon cancer cell growth suppression,
      and 2) inhibition of the blood supply of the tumor via angiogenesis. Further
      research is warranted to test 6-gingerol in animal studies as a potential
      anticancer plant bioactive in the complementary treatment of cancer.

PMID- 19117331
TI  - Anti-inflammatory effect of Ishige okamurae ethanolic extract via inhibition of
      NF-kappaB transcription factor in RAW 264.7 cells.
AB  - Nowadays, much attention has been paid to the development of anti-inflammatory
      agents from marine natural resources. As a result of screening anti-inflammatory
      agents from marine algae using immunoassay, we found for the first time that
      ethanolic extract of Ishige okamurae (IO) classified into brown algae was
      effective in inhibiting the production of inflammatory mediators, such as tumor
      necrosis factor-alpha, interleukin-1beta, interleukin-6 and prostaglandin E(2),
      in RAW264.7 cells stimulated by lipopolysaccharide, compared with dexamethasone
      and aspirin used as positive control in this study. Moreover, transcriptional
      activation of NF-kappaB transcription factor that regulates the expression of
      these inflammatory mediators was also examined using reporter gene assay and
      western blot analysis. It was observed that IO extract exerted anti-inflammatory
      effect via inactivation of NF-kappaB transcription factor in macrophages. In
      addition, the expression and activity of matrix metalloproteinase-2 and 9 that
      play an important role in chronic inflammation were decreased in dose-dependent
      manner in the presence of IO extract in HT1080 cells. The above results suggest
      that IO extract can inhibit inflammation through inactivation of NF-kappaB
      transcription factor in macrophage.

PMID- 19117332
TI  - Dolichandroside A, a new alpha-glucosidase inhibitor and DPPH free-radical
      scavenger from Dolichandrone falcata seem.
AB  - A new phenylpropanoid glycoside, dolichandroside-A, together with seven known
      compounds alpha-lapachone, lapachol, aloesaponarin II, 8-hydroxydehydroiso-alpha
      lapachone, beta-sitosterol, 3,8-dihydroxydehydroiso-alpha-lapachone and
      verbascoside were isolated from the active ethyl acetate soluble extract of
      heartwood of Dolichandrone falcata. All except for dolichandroside-A are known
      compounds, but have been isolated for the first time from this plant. The
      structure of all these compounds was determined on the basis of 1D- and 2D-NMR
      spectral data. All the isolates were tested for alpha-glucosidase inhibitory and
      DPPH radical scavenging activity. This is the first report identifying DPPH
      scavenging activity and alpha-glucosidase inhibitory activity in D. falcata.
      Furthermore, along with a new compound, dolichandroside-A, this study also
      assigns for the first time alpha-glucosidase inhibitory activity to verbascoside
      and aloe saponarin-II.

PMID- 19117333
TI  - Lipid extract from completely sporoderm-broken germinating Ganoderma sinensis
      spores elicits potent antitumor immune responses in human macrophages.
AB  - Ganoderma sinensis has been used widely in Oriental countries for the prevention
      and treatment of various diseases including cancer. Previous studies have shown
      that the lipid extract from Ganoderma exhibits direct cytotoxicity against tumor
      cells. Here, it is reported that the lipid extract from germinating G. sinensis
      spores, at lower concentrations that have no direct tumoricidal activity, induce
      potent antitumor immune responses in human monocytes/macrophages. Upon
      stimulation with the lipid extract, monocytes/macrophages exhibited markedly
      increased production of proinflammatory cytokines and surface expression of
      costimulatory molecules. Conditioned medium from stimulated cells effectively
      suppressed the growth of tumor cells. Apparently, the lipid extract triggered
      macrophage activation via a mechanism different from that associated with LPS.
      Moreover, it was observed that the lipid extract could partially re-establish the
      antitumor activity of the immunosuppressive tumor-associated macrophages. These
      results indicated that in addition to its direct tumoricidal activity, the lipid
      extract from G. sinensis spores could exert antitumor activity by stimulating the
      activation of human monocytes/macrophages.

PMID- 19117334
TI  - Vocal cord immobility caused by the long-standing impaction of a fishbone in the
      hypopharynx.
AB  - Vocal cord immobility is a rare presentation of an impacted fishbone in the
      pharynx. The mechanisms can be classified into either mechanical articular
      fixation or direct/indirect neuropathy of the recurrent laryngeal nerve. We
      report a case of vocal cord immobility secondary to long-standing impaction of a
      fishbone in the hypopharynx for at least 9 months. The diagnosis was made by
      computed tomography (CT) and rigid laryngoscopy because no reliable history was
      available. The cricoarytenoid joint was not fixed and the function of the vocal
      cords returned one month after removal of the fishbone. The mechanism of the
      vocal cord immobility was an injury to the recurrent laryngeal nerve due to the
      chronic inflammatory reaction in the paraglottic space.

PMID- 19117335
TI  - Defective inhibition and inter-regional phase synchronization in pianists with
      musician's dystonia: an EEG study.
AB  - Recent neurophysiological studies have associated focal-task specific dystonia
      (FTSD) with impaired inhibitory function. However, it remains unknown whether
      FTSD also affects the inhibition (INH) of long-term overlearned motor programs.
      Consequently, we investigated in a Go/NoGo paradigm the neural correlates
      associated with the activation (ACT) and inhibition of long-term overlearned
      motor memory traces in pianists with musician's dystonia (MD), a form of FTSD,
      during a relevant motor task under constraint timing conditions with multichannel
      EEG. In NoGo trials, the movement related cortical potentials showed a positive
      shift after the NoGo signal related to inhibition and was significantly smaller
      over sensorimotor areas in musicians with MD. Further, we observed an increase at
      850-900 ms in the power of beta oscillations which was significantly weaker for
      the patient group. The role of the inter-electrode phase coupling in the
      sensorimotor integration of inhibitory processes turned out to be the most
      relevant physiological marker: the global phase synchronization during INH
      exhibited an increase between 230 and 330 ms and 7-8 Hz, increase which was
      significantly smaller for pianists with MD. This effect was due to a weaker phase
      synchronization between the supplementary motor cortex and left premotor and
      sensorimotor electrodes in patients. Thus, our findings support the hypothesis of
      a deficient phase coupling between the neuronal assemblies required to inhibit
      motor memory traces in patients with MD. EMG recorded from the right flexor
      pollicis longus muscle confirmed that patients with MD had a disrupted INH in
      NoGo trials.

PMID- 19117336
TI  - IDH1 mutations at residue p.R132 (IDH1(R132)) occur frequently in high-grade
      gliomas but not in other solid tumors.
AB  - Systematic sequence profiling of the Glioblastoma Multiforme (GBM) genome has
      recently led to the identification of somatic mutations in the isocitrate
      dehydrogenase 1 (IDH1) gene. Interestingly, only the evolutionarily conserved
      residue R132 located in the substrate binding site of IDH1 was found mutated in
      GBM. At present, the occurrence and the relevance of p.R132 (IDH1(R132)) variants
      in tumors other than GBMs is largely unknown. We searched for mutations at
      position R132 of the IDH1 gene in a panel of 672 tumor samples. These included
      high-grade glioma, gastrointestinal stromal tumors (GIST), melanoma, bladder,
      breast, colorectal, lung, ovarian, pancreas, prostate, and thyroid carcinoma
      specimens. In addition, we assessed a panel of 84 cell lines from different tumor
      lineages. Somatic mutations affecting the IDH1(R132) residue were detected in 20%
      (23 of 113) high-grade glioma samples. In addition to the previously reported
      p.R132H and p.R132S alleles, we identified three novel somatic mutations
      (p.R132C, p.R132G, and p.R132L) affecting residue IDH1(R132) in GBM. Strikingly,
      no IDH1 mutations were detected in the other tumor types. These data indicate
      that cancer mutations affecting IDH1(R132) are tissue-specific, and suggest that
      it plays a unique role in the development of high-grade gliomas.

PMID- 19117337
TI  - Dopamine agonists restore cortical plasticity in patients with idiopathic
      restless legs syndrome.
AB  - In the present work, we aimed at assessing whether patients with idiopathic
      restless legs syndrome (RLS) showed alterations of sensory-motor plasticity, an
      indirect probe for motor learning, within the motor cortex (M1). Previous
      findings suggest that learning in human M1 occurs through LTP-like mechanisms. To
      test our hypothesis, we employed the paired associative stimulation (PAS)
      protocol by transcranial magnetic stimulation (TMS), which is able to induce LTP
      like effects in the motor cortex of normal subjects. Twelve patients with
      idiopathic RLS and 10 age- and sex-matched control subjects were recruited. PAS
      protocol consisted of 0.05 Hz electrical median nerve stimulation (90 stimuli),
      paired with 0.05 Hz TMS (90 stimuli) over the hot spot for stimulating the
      abductor pollicis brevis (APB) muscle given 25 milliseconds after the onset of
      the electrical stimulus. Corticospinal excitability recorded in APB muscle, as
      indexed by MEP obtained after single stimulus, was tested before and up to 30
      minutes after PAS protocol. Eight of 12 patients were studied before and after 4
      weeks of dopaminergic treatment. PAS protocol increased significantly
      corticospinal excitability as long as 30 minutes in healthy subjects. On the
      contrary, PAS protocol did not change the amplitude of MEPs in patients with
      idiopathic RLS without treatment. PAS associative plasticity was restored after 4
      weeks of dopaminergic treatment. Our data demonstrated that associative sensory
      motor plasticity, an indirect probe for motor learning, is impaired in idiopathic
      RLS patients but may be reverted to normal after dopaminergic treatment.

PMID- 19117338
TI  - Stereotactic radiotherapy for pancreatic cancer?

PMID- 19117339
TI  - A novel ferritin light chain gene mutation in a Japanese family with
      neuroferritinopathy: description of clinical features and implications for
      genotype-phenotype correlations.
AB  - Neuroferritinopathy is a hereditary neurodegenerative disorder caused by
      mutations in the ferritin light chain gene (FTL1). The cardinal features are
      progressive movement disturbance, hypoferritinemia, and iron deposition in the
      brain. To date, five mutations have been described in Caucasian and Japanese
      families, but the genotype-phenotype correlations remain to be established. We
      identified a novel FTL1 mutation (exon 4, c.641/642, 4-nucletotide duplication)
      in a Japanese family and compared the clinical traits with those previously
      reported. All mutations but one are insertions in exon 4, resulting in
      frameshifts. Clinical features are similar among patients with the same
      mutations. Middle-age onset chorea is common in patients with insertions in the
      5' portion of exon 4 including our cases, whereas patients with insertions in the
      3' portion of exon 4 develop early-onset tremor, suggesting genotype-phenotype
      correlations. In this family, male predominance and normal serum ferritin levels
      are characteristic.

PMID- 19117340
TI  - Bendamustine: a new look at an old drug.
AB  - Alkylating agents form the basis of most combination treatment regimens for low
      grade lymphoproliferative disorders. Bendamustine is a unique alkylating agent
      that has distinctive preclinical activity in cell lines resistant to other
      alkylators. Furthermore, clinical activity has been demonstrated in patients with
      alkylating agent resistant disease. Recently, larger studies have been organized
      to study the clinical effects of bendamustine further. In indolent B-cell non
      Hodgkin lymphoma that is resistant to rituximab, bendamustine induced a remission
      in 77% of patients. Myelosuppression was identified as the most common toxicity.
      In 2 studies of similar populations of patients, the combination of bendamustine
      and rituximab induced remission 90% of patients with a median progression-free
      survival of 23-24 months. The overall remission rate was 59% in a prospective,
      randomized study of untreated patients with chronic lymphocytic leukemia, which
      was significantly greater than the rate of 26% in the chlorambucil control arm (P
      < 0.001). Combined with rituximab, bendamustine induces a remission in 67% of
      patients with relapsed or refractory chronic lymphocytic leukemia. Bendamustine
      is an active agent for the treatment of low-grade lymphoproliferative disorders
      and more study is needed to determine which dose and schedule is optimal, and
      which patients will derive the greatest benefit from its use.

PMID- 19117341
TI  - Cost-effectiveness analysis of lapatinib in HER-2-positive advanced breast
      cancer.
AB  - BACKGROUND: A recent clinical trial demonstrated that the addition of lapatinib
      to capecitabine in the treatment of HER-2-positive advanced breast cancer (ABC)
      significantly increases median time to progression. The objective of the current
      analysis was to assess the cost-effectiveness of this therapy from the US
      societal perspective. METHODS: A Markov model comprising 4 health states (stable
      disease, respond-to-therapy, disease progression, and death) was developed to
      estimate the projected-lifetime clinical and economic implications of this
      therapy. The model used Monte Carlo simulation to imitate the clinical course of
      a typical patient with ABC and updated with response rates and major adverse
      effects. Transition probabilities were estimated based on the results from the
      EGF100151 and EGF20002 clinical trials of lapatinib. Health state utilities,
      direct and indirect costs of the therapy, major adverse events, laboratory tests,
      and costs of disease progression were obtained from published sources. The model
      used a 3% discount rate and reported in 2007 US dollars. RESULTS: Over a
      lifetime, the addition of lapatinib to capecitabine as combination therapy was
      estimated to cost an additional $19,630, with an expected gain of 0.12 quality
      adjusted life years (QALY) or an incremental cost-effectiveness ratio (ICER) of
      $166,113 per QALY gained. The 95% confidence limits of the ICER ranged from
      $158,000 to $215,000/QALY. A cost-effectiveness acceptability curve indicated
      less than 1% probability that the ICER would be lower than $100,000/QALY.
      CONCLUSIONS: Compared with commonly accepted willingness-to-pay thresholds in
      oncology treatment, the addition of lapatinib to capecitabine is not clearly cost
      effective; and most likely to result in an ICER somewhat higher than the societal
      willingness-to-pay threshold limits.

PMID- 19117342
TI  - Psychogenic nocturnal stridor in a child: a case report.

PMID- 19117343
TI  - Esophageal tumor length is independently associated with long-term survival.
AB  - BACKGROUND: Esophageal cancer staging uses tumor depth as the sole criterion for
      assessment of the primary tumor (pT). To the authors' knowledge the impact of
      esophageal tumor length on long-term outcome and the esophageal cancer staging
      system has not been fully evaluated in the current era. METHODS: All esophageal
      cancer patients (n = 209) undergoing surgery from 1995 to 2005 who did not
      receive preoperative chemotherapy or radiotherapy were reviewed. Maximum
      esophageal tumor length along a craniocaudal axis was determined pathologically
      after surgical resection. Univariate and multivariate analyses were used to
      assess the impact of esophageal tumor length (< or = 3 cm vs >3 cm) on long-term
      survival. RESULTS: Esophageal tumor length was closely associated with long-term
      survival (hazards ratio [HR] of 6.14 [95% confidence interval (95% CI), 4.1
      9.25]; 5-year survival: < or = 3 cm = 68%, >3 cm = 10% [P < .001]). Multivariate
      Cox regression analyses demonstrated tumor length (HR of 2.13 [95% CI, 1.26
      3.63]) was found to be a significant independent predictor of long-term survival
      even when controlled for sex, age, tumor location, histology, margin positivity,
      surgical procedure, and current pTNM criteria. The incorporation of tumor length
      in pTNM staging significantly improves the ability to predict the long-term
      survival of patients (5-year survival for patients with tumors < or = 3 cm and
      stages I, IIA, IIB, and III disease = 86%, 62%, 49%, and 22%, respectively;
      survival for patients with tumors measuring >3 cm and stages I, IIA, IIB, and III
      disease = 27%, 22%, 0%, and 8%, respectively [P < .1]). CONCLUSIONS: Esophageal
      tumor length is an independent predictor of long-term survival in the current era
      and should be considered for incorporation into the current esophageal cancer
      staging system to better predict long-term survival and identify high-risk
      patients for postoperative therapy.

PMID- 19117344
TI  - Phase 1/2 study of intravenous paclitaxel and oral cyclophosphamide in pretreated
      metastatic urothelial bladder cancer patients.
AB  - BACKGROUND: To the authors' knowledge, no previous studies have been reported
      with the combination of paclitaxel and oral cyclophosphamide in patients with
      metastatic bladder cancer. A phase 1/2 study was conducted of paclitaxel in
      combination with oral cyclophosphamide for patients with advanced urothelial
      bladder cancer who had been previously treated with gemcitabine/cisplatin
      chemotherapy as first-line metastatic treatment. METHODS: This was a single-arm
      phase 1/2 study. Patients were treated with paclitaxel and oral cyclophosphamide
      at 3-week intervals until disease progression or irreversible toxicity occurred.
      Primary endpoints were to determine the maximum tolerated doses (MTD) and
      objective response rate; secondary endpoints were safety, time to disease
      progression (TTP), and overall survival (OS). RESULTS: Forty-four patients were
      enrolled. Dose levels of paclitaxel of 175 mg/m(2) (Day 1) and cyclophosphamide
      of 50 mg (Days 1-7 orally) (dose level I) of a 21-day cycle were tolerated
      without dose-limiting toxicities (DLTs). At a cyclophosphamide dose of 100 mg
      (dose level II) the MTD was exceeded; 3 of 6 patients experienced a DLT (grade 3
      constipation and grade 4 neutropenia and thrombocytopenia [toxicities were graded
      using National Cancer Institute Common Toxicity Criteria (version 3.0)]). Dose
      level I was expanded and determined to be the MTD. A total of 32 patients were
      treated at dose level I in the phase 2 portion. Partial responses were observed
      in 31% of patients (10 of 32 patients; 95% confidence interval [95% CI], 17%
      45%). Grade 1/2 vomiting, peripheral neuropathy, and neutropenia were the most
      common side effects, noted in 11 (34%), 8 (25%), and 10 (31%) patients,
      respectively. The median TTP was 5 months (95% CI, 2 months-7.5 months) and the
      median OS was 8 months (95% CI, 4 months-14 months). CONCLUSIONS: The combination
      of paclitaxel and cyclophosphamide is well tolerated and associated with
      promising efficacy. Further trials are needed to confirm these preliminary
      results.

PMID- 19117346
TI  - The extent of minimal residual disease reduction after the first 4-week imatinib
      therapy determines outcome of allogeneic stem cell transplantation in adults with
      Philadelphia chromosome-positive acute lymphoblastic leukemia.
AB  - BACKGROUND: Previously, the authors demonstrated the positive impact of imatinib
      on the outcome of allogeneic stem cell transplantation in adults with
      Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph-positive ALL).
      Here, the authors analyzed for risk factors that affect transplantation outcome,
      and they focused particularly on the prognostic relevance of minimal residual
      disease level at each treatment stage. METHODS: Fifty-two patients with newly
      diagnosed Ph-positive ALL who completed allogeneic stem cell transplantation
      following imatinib therapy were enrolled in this study. For minimal residual
      disease monitoring, 548 marrow samples were analyzed by a real-time quantitative
      polymerase chain reaction assay. RESULTS: After the first 4-week imatinib
      therapy, 11 patients (21.2%) achieved molecular remission, and the remaining 41
      patients had a reduction in BCR-ABL transcript levels (median, 3.21 log) from
      baseline value. The frequency of achieving a reduction in BCR-ABL transcript
      levels of at least 3 log at this stage was 36 (69.2%). Forty-eight (92.3%) of the
      52 patients received stem cell transplantation during first complete remission.
      With a median follow-up of 49 months after stem cell transplantation, the 4-year
      relapse rate and disease-free survival rate were 21.2% and 69.8%, respectively. A
      reduction in BCR-ABL transcript levels of at least 3 log after the first 4-week
      imatinib therapy was identified as the most powerful predictor of lower relapse
      (12.1% vs 45.1%, P = .011) and better disease-free survival (82.1% vs 41.7%, P =
      .009) rates. CONCLUSIONS: Prospective assessment of the extent of minimal
      residual disease reduction after the first 4-week imatinib therapy may allow the
      authors to identify subgroups of Ph-positive ALL transplants at high risk of
      relapse.

PMID- 19117345
TI  - Efficacy of imatinib dose escalation in patients with chronic myeloid leukemia in
      chronic phase.
AB  - BACKGROUND: Imatinib mesylate given orally at a daily dose of 400 mg is the
      standard of care as initial therapy for patients with chronic myeloid leukemia
      (CML) in chronic phase (CML-CP). Treatment guidelines propose dose escalation
      based on clinical assessments of disease response. METHODS: Response and survival
      were analyzed in a cohort of patients (n = 106) with newly diagnosed CML-CP who
      were enrolled on the International Randomized Study of Interferon and STI571
      (IRIS) trial, who began treatment with imatinib at a dose of 400 mg daily, and
      who subsequently underwent dose escalation to either 600 mg or 800 mg daily.
      Reasons for dose escalation were evaluated retrospectively based on 2 sets of
      criteria: the IRIS protocol-defined criteria (n = 39 patients) and the European
      LeukemiaNet (ELN) recommendations (n = 48 patients). RESULTS: Among all 106
      patients who underwent dose escalation, the rates of freedom from progression to
      accelerated phase or blast phase and overall survival were 89% and 84% at 3 years
      after dose increase, respectively. A cytogenetic response was obtained in 42% of
      patients who had their dose escalated based on protocol criteria and in 38% of
      patients who had their dose escalated according to the ELN recommendations.
      CONCLUSIONS: The results from this retrospective analysis supported imatinib dose
      escalation as an appropriate initial option for patients with CML-CP who were
      experiencing suboptimal cytogenetic response or resistance.

PMID- 19117347
TI  - High serum des-gamma-carboxy prothrombin level predicts poor prognosis after
      radiofrequency ablation of hepatocellular carcinoma.
AB  - BACKGROUND: Currently, surgical resection is considered the first-line treatment
      for early stage hepatocellular carcinoma (HCC). Radiofrequency ablation (RFA) has
      been an alternative choice for unresectable HCC. However, RFA is expected to have
      similar therapeutic efficacy for early stage HCC with fewer invasions. METHODS:
      The authors retrospectively analyzed 199 patients who underwent surgery and 209
      patients who underwent RFA for HCC with a maximum diameter of < or = 3 cm and
      tumors numbering < or = 3. All patients were complicated with Child-Pugh A
      cirrhosis. RESULTS: The 3- and 5-year survival rates of the resection (90.3%,
      79.0%, respectively) and RFA groups were similar (87.4%, 74.8). The 1- and 3-year
      tumor recurrence-free survival rates of the resection group (83.1%, 51.0%,
      respectively) were higher than in the RFA group (82.7%, 41.8%; P = .011).
      Multivariate analysis identified prothrombin time > or = 80% (hazard ratio [HR],
      2.72; 95% confidence interval [CI], 1.56-4.74; P < .001) as an independent
      prognostic factor for survival in the resection group. Des-gamma-carboxy
      prothrombin (DCP) <100 arbitrary units (AU)/L (HR, 5.49; CI, 2.23-13.5; P < .001)
      and platelet count > or = 1.0 x 10(5) (HR, 2.70; CI, 1.24-5.88; P = .012) were
      significant markers in the RFA group. Among patients with DCP > or = 100 AU/L,
      treatment procedure (HR, 1.26; CI, 1.04-1.53; P = .020) was a significant
      prognostic factor for survival. CONCLUSIONS: High DCP levels reflect the biologic
      aggressiveness and progression of HCC tumors. In the aforementioned cases, we
      recommend surgical resection rather than RFA for such patients.

PMID- 19117348
TI  - Early changes in tumor size in patients treated for advanced stage nonsmall cell
      lung cancer do not correlate with survival.
AB  - BACKGROUND: In clinical trials, change in tumor size is used to stratify patients
      into response categories. The objective of the current study was to: 1) determine
      whether early change in the tumor size were correlated with survival in patients
      with advanced nonsmall cell lung cancer (NSCLC) using modified response
      categories from the Response Evaluation Criteria in Solid Tumors (RECIST), and 2)
      to determine whether there was an optimal percentage change in tumor size that
      could be used to define a partial response that also correlated with survival.
      METHODS: A total of 99 consecutive patients presenting for the treatment of
      advanced NSCLC during the year 2003 who had computed tomography (CT) scans before
      and after treatment available for review were included in the study. The largest
      target thoracic lesion was measured on CT before treatment, and again 2 months to
      3 months after the initiation of treatment. Percent change in tumor size was
      calculated. The relation between tumor response and patient survival was
      investigated. RESULTS: There was no definite relation noted between early tumor
      response and patient survival (P = .754). Patients who had any initial reduction
      in tumor size were not found to have a significantly different survival compared
      with patients with initial disease progression (P = .580). In addition, there was
      no particular percent reduction in tumor size that was found to optimally
      correlate with survival. CONCLUSIONS: There is no evidence of a relation between
      early changes in tumor size and survival among patients with advanced stage
      NSCLC. To predict survival in patients with advanced NSCLC, response criteria
      other than change in lesion size are needed.

PMID- 19117349
TI  - Promoting physical activity in childhood cancer survivors: results from the
      Childhood Cancer Survivor Study.
AB  - BACKGROUND: Although physical activity may modify the late effects of childhood
      cancer treatment, from 20% to 52% of adult survivors are sedentary. The authors
      of this report sought to identify modifiable factors that influence survivors'
      participation in physical activity. METHODS: Structural equation modeling of data
      were derived from the Childhood Cancer Survivors Study of adult survivors
      (current mean age, 30.98 years; mean years since diagnosis, 23.74; mean age at
      diagnosis, 9.25 years) who were diagnosed between 1970 and 1986. RESULTS:
      Approximately 40% of the variance in male survivors' recent participation versus
      nonparticipation in physical activity was explained directly and/or indirectly by
      self-reported health fears (P = .01), perceived primary-care physician (PCP)
      expertise (P = .01), baseline exercise frequency (P < or = .001), education level
      (P = .01), self-reported stamina (P = .01), cancer-related pain (P < or = .001),
      fatigue (P < or = .001), age at diagnosis (P = .01), cancer-related anxiety (P <
      or = .001), motivation (P = .01), affect (P = .01), and discussion of subsequent
      cancer risk with the PCP (P < or = .001) (N = 256; chi-square test statistic =
      53.38; degrees of freedom [df] = 51; P = .38, Comparative Fit Index [CFI] =
      1.000; Tucker Lewis Index [TLI] = 1.000; root mean square of approximation
      [RMSEA] = 0.014; weighted root mean square residual [WRMR] = 0.76). Thirty-one
      percent of the variance in women' recent physical activity participation was
      explained directly and/or indirectly by self-reported stamina (P < or = .001),
      fatigue (P = .01), baseline exercise frequency (P = .01), cancer-related pain (P
      < or = .001), cancer-related anxiety (P = .01), recency of visits with PCP
      (<0.001), quality of interaction with the PCP (P = .01), and motivation (P < or =
      .001; N = 366; chi-square test statistic = 67.52; df = 55; P = .12; CFI = 0.98;
      TLI = 0.98; RMSEA = 0.025; WRMR = 0.76). CONCLUSIONS: Gender-tailored
      intervention strategies in which providers specifically target motivation, fear,
      and affect may support physical activity in childhood cancer survivors.

PMID- 19117350
TI  - Phase 1 study of an oxaliplatin and etoposide regimen in pediatric patients with
      recurrent solid tumors.
AB  - BACKGROUND: The combination of a platinating agent and etoposide has induced
      responses in various pediatric tumors. The study estimated the maximum tolerated
      dose (MTD) of an oxaliplatin and etoposide regimen in children with recurrent
      solid tumors. METHODS: Oxaliplatin was administered on Day 1 and etoposide on
      Days 1 to 3 of each 21-day course. Cohorts of 3 to 6 patients were enrolled at 3
      dose levels: 1) oxaliplatin at a dose of 130 mg/m(2) and etoposide at a dose of
      75 mg/m(2), 2) oxaliplatin at a dose of 130 mg/m(2) and etoposide at a dose of
      100 mg/m(2), and 3) oxaliplatin at a dose of 145 mg/m(2) and etoposide at a dose
      of 100 mg/m(2). Calcium and magnesium infusions were used at dose level 3 in an
      attempt to escalate the oxaliplatin dose past the single-agent MTD. RESULTS: The
      16 patients received a total of 63 courses. At dose level 1, dose-limiting
      epistaxis, neuropathy, and neutropenia occurred in 1 of 6 patients. No dose
      limiting toxicity (DLT) occurred at dose level 2 (n = 6). At dose level 3, 2 of 4
      patients experienced dose-limiting neutropenia; none experienced grade 3 or 4
      acute neuropathy. Six patients required prolongation of the oxaliplatin infusion
      because of acute sensory neuropathy. Responses were observed in patients with
      medulloblastoma (1 complete response) and pineoblastoma (1 partial response); 3
      others with atypical teratoid rhabdoid tumor, ependymoma, and soft tissue sarcoma
      had prolonged disease stabilization. CONCLUSIONS: The MTD of this regimen was
      found to be oxaliplatin at a dose of 130 mg/m(2) given on Day 1 and etoposide at
      a dose of 100 mg/m(2)/d given on Days 1 to 3. Neutropenia was found to be the
      DLT. Calcium and magnesium infusions did not allow escalation of the oxaliplatin
      dose. The combination was well-tolerated and demonstrated antitumor activity.

PMID- 19117351
TI  - Stereotactic radiotherapy for unresectable adenocarcinoma of the pancreas.
AB  - BACKGROUND: The authors report on the local control and toxicity of stereotactic
      body radiotherapy (SBRT) for patients with unresectable pancreatic
      adenocarcinoma. METHODS: Seventy-seven patients with unresectable adenocarcinoma
      of the pancreas received 25 gray (Gy) in 1 fraction. Forty-five patients (58%)
      had locally advanced disease, 11 patients (14%) had medically inoperable disease,
      15 patients (19%) had metastatic disease, and 6 patients (8%) had locally
      recurrent disease. Nine patients (12%) had received prior chemoradiotherapy.
      Sixteen patients (21%) received between 45 to 54 Gy of fractionated radiotherapy
      and SBRT. Various gemcitabine-based chemotherapy regimens were received by 74
      patients (96%), but 3 patients (4%) did not receive chemotherapy until they had
      distant failure. RESULTS: The median follow-up was 6 months (range, 3-31 months)
      and, among surviving patients, it was 12 months (range, 3-31 months). The overall
      rates of freedom from local progression (FFLP) at 6 months and 12 months were 91%
      and 84%, respectively. The 6- and 12-month isolated local recurrence rates were
      5% and 5%, respectively. There was no difference in the 12-month FFLP rate based
      on tumor location (head/uncinate, 91% vs body/tail, 86%; P = .52). The
      progression-free survival (PFS) rates at 6 months and 12 months were 26% and 9%,
      respectively. The PFS rate at 6 months was superior for patients who had
      nonmetastatic disease versus patients who had metastatic disease (28% vs 15%; P =
      .05). The overall survival (OS) rates at 6 months and 12 months from SBRT were
      56% and 21%, respectively. Four patients (5%) experienced grade > or = 2 acute
      toxicity. Three patients (4%) experienced grade 2 late toxicity, and 7 patients
      (9%) experienced grade > or = 3 late toxicity. At 6 months and 12 months, the
      rates of grade > or = 2 late toxicity were 11% and 25%, respectively.
      CONCLUSIONS: SBRT for pancreatic adenocarcinoma was effective for local control
      with associated risk of toxicity and should be used with rigorous attention to
      quality assurance. Efforts to reduce complications are warranted. Distant
      metastases account for the vast majority of disease-related mortality.

PMID- 19117352
TI  - The volume to be irradiated during selective neck irradiation in nasopharyngeal
      carcinoma: analysis of the spread patterns in lymph nodes by magnetic resonance
      imaging.
AB  - BACKGROUND: For this report, the authors analyzed the spread pattern of lymph
      node (LN) metastases in patients with nasopharyngeal carcinoma (NPC) by using
      magnetic resonance imaging (MRI). In addition, the efficacy of selective neck
      irradiation was assessed based on the volume irradiated. METHODS: This was a
      retrospective review of data from 924 patients with newly diagnosed and
      nondisseminated NPC who underwent MRI and treatment between January 2003 and
      December 2004. RESULTS: According to the criteria for involved LNs detected by
      MRI, the incidence of LN metastases was 85.1% (786 of 924 patients). An analysis
      of the distribution of LN metastases in these 786 patients demonstrated that the
      retropharyngeal LNs (RLN) and Level II LNs were the most frequently involved
      regions, followed in order by Level III and Level V LNs, Level IV LNs, and
      supraclavicular fossa (SCF) LNs. In only 4 of 786 patients (0.5%) did metastasis
      skip LNs in their progression. In addition, 5 of 354 patients (1.4%) who had
      unilateral, higher level LN metastases (including RLNs and Level II LNs) had
      contralateral or bilateral, lower level LN involvement (including Level III,
      Level IV, Level V, and SCF LNs). In patients who had LN-negative (N0) disease,
      the risks of regional recurrence and distant metastasis did not differ
      statistically between patients with inferior border of the neck irradiation field
      either at the cricoid cartilage or below the cricoid cartilage. CONCLUSIONS: By
      using MRI, LN metastases spread in an orderly fashion from higher level LNs to
      lower level LNs. The current results did not support prophylactic irradiation of
      Level IV and SCF LNs in patients who were negative for LN metastases, and these
      concepts need to be tested clinically before they may be recommended generally.

PMID- 19117353
TI  - Induction of human tumor-associated differentially expressed gene-12 (TADG
      12/TMPRSS3)-specific cytotoxic T lymphocytes in human lymphocyte antigen-A2.1
      positive healthy donors and patients with advanced ovarian cancer.
AB  - BACKGROUND: Tumor-associated differentially expressed gene-12 (TADG-12) is a
      serine protease recently found highly differentially expressed in epithelial
      ovarian cancer. The goal of this study was to identify potential immunogenic
      peptides derived from TADG-12 for immunotherapy of ovarian carcinoma. METHODS: A
      bioinformatics approach (ie, the BIMAS algorithm, National Institutes of Health,
      http://bimas.dcrt.nih.gov/molbio/hla_bind) was used to identify multiple
      immunogenic peptides derived from TADG-12 that bind to human leukocyte antigen
      A2.1 and elicit peptide-specific human cytotoxic T lymphocyte (CTL) responses in
      healthy individuals and in patients with advanced stage ovarian cancer. RESULTS:
      CD8+ CTL populations generated against 5 TADG-12-derived peptides were
      consistently able to induce lysis of autologous peptide-loaded target cells above
      background. Importantly, TADG-12 YLPKSWTIQV peptide-specific CTLs from healthy
      donors and ovarian cancer patients were found to effectively kill ovarian cancer
      cells naturally expressing TADG-12. Cytotoxicity was significantly inhibited by
      anti-human lymphocyte antigen (HLA)-A2.1 (BB7-2) and anti-HLA class I (W6 of 32)
      monoclonal antibodies, whereas natural killer-sensitive K562 cells were not
      lysed. TADG-12 YLPKSWTIQV peptide-specific CTL precursor frequency was low in
      peripheral blood leukocytes of normal donors and ovarian cancer patients, as
      determined by interferon-gamma production in enzyme-linked immunosorbent spot
      forming cell assays. Intracellular cytokine expression measured by flow cytometry
      after OKT-3 monoclonal antibody stimulation showed a type 1 cytokine profile in
      YLPKSWTIQV peptide-specific CTLs. CONCLUSIONS: The TADG-12 YLPKSWTIQV peptide is
      an immunogenic epitope in ovarian tumors and may represent an attractive target
      for immunotherapy of ovarian cancer. These data may pave the way for TADG-12
      peptide-derived cell-based therapy, including dendritic cell immunotherapy, for
      the vaccination of ovarian cancer patients harboring chemotherapy-resistant or
      residual disease.

PMID- 19117355
TI  - Evaluation of the use of prophylactic cranial irradiation in small cell lung
      cancer.
AB  - BACKGROUND: Prophylactic cranial irradiation has been used in patients with small
      cell lung cancer to reduce the incidence of brain metastasis after primary
      therapy. The purpose of this study was to evaluate the effects of prophylactic
      cranial irradiation (PCI) on overall survival and cause-specific survival.
      METHODS: A total of 7995 patients with limited stage small cell lung cancer
      diagnosed between 1988 and 1997 were retrospectively identified from centers
      participating in the National Cancer Institute's Surveillance, Epidemiology, and
      End Results (SEER) Program. Of them, 670 were identified as having received PCI
      as a component of their first course of therapy. Overall survival and cause
      specific survival were estimated by the Kaplan-Meier method, comparing patients
      treated with or without prophylactic whole-brain radiotherapy. The Cox
      proportional hazards model was used in the multivariate analysis to evaluate
      potential prognostic factors. RESULTS: The median follow-up time was 13 months
      (range, 1 month to 180 months). Overall survival at 2 years, 5 years, and 10
      years was 23%, 11%, and 6%, respectively, in patients who did not receive PCI. In
      patients who received PCI, the 2-year, 5-year, and 10-year overall survival rates
      were 42%, 19%, and 9%, respectively (P =or <.001). The cause-specific survival
      rate at 2 years, 5 years, and 10 years was 28%, 15%, 11%, respectively, in
      patients who did not receive PCI and 45%, 24%, 17%, respectively, in patients who
      did receive PCI (P =or <.001). On multivariate analysis of cause-specific and
      overall survival, age at diagnosis, sex, grade, extent of primary disease, size
      of disease, extent of lymph node involvement, and PCI were found to be
      significant (P = or<.001). The hazards ratios for disease-specific and all cause
      mortality were 1.13 and 1.11, respectively, for those not receiving PCI.
      CONCLUSIONS: Significantly improved overall and cause-specific survival was
      observed in patients treated with prophylactic cranial irradiation on unadjusted
      and adjusted analyses. This study concurs with the previously published European
      experience. Prophylactic cranial irradiation should be considered for patients
      with limited stage small cell lung cancer.

PMID- 19117356
TI  - Daily energy expenditure, physical activity, and weight loss in Parkinson's
      disease patients.
AB  - Patients with Parkinson's disease (PD) commonly exhibit weight loss (WL) which
      investigators attribute to various factors, including elevated energy
      expenditure. We tested the hypothesis that daily energy expenditure (DEE) and its
      components, resting energy expenditure (REE) and physical activity (PA) energy
      expenditure (PAEE), are elevated in WL compared with weight stable (WS) PD
      patients. We measured DEE in 10 PD WL patients and 10 PD WS patients using doubly
      labeled water (DLW). PAEE was estimated with DLW, activity monitors, and activity
      questionnaires. REE was measured with indirect calorimetry. We evaluated energy
      intake (EI) with a patient's 3-day food diary. Data was assessed employing SPSS,
      Spearman correlation coefficients, and Bland and Altman plots. There was no
      difference in DEE between the WL and WS groups measured with DLW. There were no
      differences in REE and EI between groups. DEE (r = 0.548, P < 0.05) and PAEE (r =
      0.563, P < 0.01) are related with caloric intake. The WL group had higher PA than
      the WS group (P < 0.042) only when measured with wrist activity monitors. Results
      suggest that WL in PD patients cannot be fully explained by an increase in DEE.
      Large longitudinal studies to examine multiple relationships between variables
      might provide us with a better understanding of WL among PD patients.

PMID- 19117354
TI  - Meta-analysis of sentinel lymph node positivity in thin melanoma (<or=1 mm).
AB  - BACKGROUND: Despite the lack of an established survival benefit of sentinel lymph
      node (SLN) biopsy, this technique has been increasingly applied in the staging of
      thin (<or=1 mm) melanoma patients, without clear evidence to support this
      recommendation. The authors performed a meta-analysis to estimate the risk,
      potential predictors, and outcome of SLN positivity in this group of patients.
      METHODS: MEDLINE, EMBASE, and Cochrane databases were searched for rates of SLN
      positivity in patients with thin melanoma. The methodologic quality of included
      studies was assessed using the Methodological Index for Non-Randomized Studies
      criteria. Heterogeneity was assessed using the Cochran Q statistic, and
      publication bias was examined through funnel plot and the Begg and Mazumdar
      method. Overall SLN positivity in thin melanoma patients was estimated using the
      DerSimonial-Laird random effect method. RESULTS: Thirty-four studies comprising
      3651 patients met inclusion criteria. The pooled SLN positivity rate was 5.6%.
      Significant heterogeneity among studies was detected (P = .005). There was no
      statistical evidence of publication bias (P = .21). Eighteen studies reported
      select clinical and histopathologic data limited to SLN-positive patients (n =
      113). Among the tumors from these patients, 6.1% were ulcerated, 31.5%
      demonstrated regression, and 47.5% were Clark level IV/V. Only 4 melanoma-related
      deaths were reported. CONCLUSIONS: Relatively few patients with thin melanoma
      have a positive SLN. To the authors' knowledge, there are no clinical or
      histopathologic criteria that can reliably identify thin melanoma patients who
      might benefit from this intervention. Given the increasing diagnosis of thin
      melanoma, in addition to the cost and potential morbidity of this procedure,
      alternative strategies to identify patients at risk for lymph node disease are
      needed.

PMID- 19117357
TI  - Zonisamide for essential tremor: an evaluator-blinded study.
AB  - In this evaluator-blinded open-treatment trial, subjects with moderate/severe
      upper limb essential tremor were titrated to 300 mg/day zonisamide, or adjusted
      to a lesser dose if symptoms warranted, as monotherapy or as adjunct to stable
      antitremor medication, followed by a 12-week extension phase. The primary
      efficacy outcome variables were blinded rater videotaped/drawing tremor score
      changes at the Treatment and Extension visits compared to Baseline, based on Fahn
      Tolosa-Marin and Postural Tremor Scales. Subjects also rated Functional
      Disabilities. Primary outcomes showed reduced tremor scores at the Treatment (P <
      0.00001, n = 25) and Extension (n = 16) visits, at mean doses of 252 and 225
      mg/day, respectively. Subject ratings indicated 200 mg/day was superior to 100
      mg/day, whereas 300 mg/day produced no additional benefit, but instead was
      associated with more adverse symptoms, most commonly somnolence, poor energy,
      imbalance, and altered taste. Future double-blind placebo-controlled trials are
      warranted.

PMID- 19117358
TI  - Validity of the Cornell scale for depression in dementia in Parkinson's disease
      with and without cognitive impairment.
AB  - Valid tools are needed to assess depression across the spectrum of cognitive
      impairment in Parkinson's disease (PD). The validity of the Cornell scale for
      depression in dementia (CSDD) was tested in a PD sample with a range of cognitive
      impairment. Psychiatric diagnoses were established according to DSM-IV-TR.
      Receiver operating characteristic curves tested the discriminant validity of the
      CSDD compared to the clinical diagnoses of major and minor depression. The curve
      for symptomatic depression had an area under the curve of 0.82. For the cut-off
      score >or= 6, sensitivity was 0.83 and specificity was 0.73; for the cut-off
      score >or= 8, sensitivity was 0.75 and specificity was 0.82. There was no
      evidence for differential measurement with respect to cognitive impairment or any
      other demographic or clinical variables. This study suggests that the CSDD is a
      valid tool for identifying depressive disorders in patients with PD across a
      spectrum of cognitive impairment.

PMID- 19117359
TI  - Walking along circular trajectories in Parkinson's disease.
AB  - We hypothesized that gait capacities would be more stressed in patients with
      Parkinson's disease (PD) when walking along curved than straight trajectories,
      owing to the complex adaptations required for this walking task. Twenty on-phase
      patients with PD and 20 healthy subjects walked eyes-open along straight and
      curved trajectories for 1 minute at self-paced cadence and velocity. Step
      frequency along straight and curved trajectories was computed from video
      recordings of the lower limbs. Step frequency was not affected by trajectory
      shape in either patients with PD or healthy subjects. Distances run by the
      patients were shorter than normal under both conditions. However, in PD,
      distances were relatively shorter during curved than straight walking; therefore,
      decreased distances in PD were connected with decreased mean step length (as the
      ratio between distance and step number). No correlation was found between the
      above mentioned variables and the severity or duration of the disease or the
      frequency of falls. Walking along curved trajectories can highlight impaired gait
      control in on-phase patients with PD, and can be suitable for the routine
      evaluation of possible walking disorders when straight walking is not
      significantly affected.

PMID- 19117361
TI  - Myoclonus-dystonia: an update.
AB  - Our knowledge of the clinical, neurophysiological, and genetic aspects of
      myoclonus-dystonia (M-D) has improved markedly in the recent years. Basic
      research has provided new insights into the complex dysfunctions involved in the
      pathogenesis of M-D. On the basis of a comprehensive literature search, this
      review summarizes current knowledge on M-D, with a focus on recent findings. We
      also propose modified diagnostic criteria and recommendations for clinical
      management.

PMID- 19117362
TI  - "Jerky" dystonia in children: spectrum of phenotypes and genetic testing.
AB  - Hyperkinetic dystonia is characterized by phasic, tremulous, and "jerky"
      movements in addition to twisting postures. We studied longitudinally 23 index
      patients with hyperkinetic dystonia from a quaternary pediatric movement disorder
      clinic in Ireland. Four clinical categories emerged: (1) Eight patients were
      diagnosed with myoclonus-dystonia, of whom seven carried heterozygous epsilon
      sarcoglycan (SGCE) mutations, including a novel deletion of exon 10. Gait
      disorder, unsteadiness, or frequent falls before 18 months were detected in all
      SGCE mutation carriers, whereas the typical neck-predominant presentation
      developed only years later. (2) One patient classified as benign hereditary
      chorea, because jerks were choreiform and continuous rather than action-induced,
      carried a heterozygous stop mutation of the TITF-1 gene (Y114X, exon 2). (3)
      Three mutation-negative patients were grouped as "myoclonic dystonia" with jerks
      only in the body regions affected by dystonia. (4) Eleven patients presented with
      a novel combination of dystonia and low amplitude poly-mini myoclonus of the
      upper limbs and pectoral muscles (D-PMM). In early childhood up to 3 years of
      age, an initial presentation with predominant gait impairment with only subtle
      jerks should prompt consideration of SGCE mutation analysis in addition to
      testing for DYT1 mutations. A causative gene for D-PMM remains to be identified.

PMID- 19117363
TI  - Haplotype analysis of the PARK 11 gene, GIGYF2, in sporadic Parkinson's disease.
AB  - Familial Parkinsonism (PARK) genes are strong candidates for conferring
      susceptibility to common forms of PD. However, most studies to date have provided
      little evidence that their common variants substantially influence disease risk.
      Recently, mutations were described in the gene, GIGYF2 (TNRC15), located at the
      PARK11 locus (2q37.1). Here, we use a haplotype tagging approach to examine
      common variation in the GIGYF2 gene and PD risk. PD cases (n = 568) and age and
      gender-matched control subjects (n = 568) were recruited from three specialist
      movement disorder clinics in Brisbane (Australia) and the Australian electoral
      roll. Twelve tagging SNPs were assessed in all subjects and haplotype and
      genotype associations were explored. Overall our findings suggest that common
      genetic variants of GIGYF2 do not significantly affect sporadic PD risk in
      Australian Caucasians.

PMID- 19117364
TI  - Progression of dysprosody in Parkinson's disease over time--a longitudinal study.
AB  - Parkinsonian speech or hypokinetic dysarthria results from a multidimensional
      impairment of phonation, articulation, and prosody. Although the dysprosody in
      Parkinson's disease (PD) is well described (alterations in speech rate and pause
      time, speech intensity and pitch variation), little is known about alterations of
      these single prosodic parameters over a longer time course. The objective of this
      study is to analyze changes of speech rate and pitch variation in patients with
      PD over time and to compare these findings with healthy controls. Patients with
      PD (N = 50; 27 male and 23 female) and n = 50 age-matched healthy controls (25
      male, 25 female) were tested and retested after at least 7 months (mean: 25.02;
      median: 21; SD: 17.44; range: 7-79 months). In the PD group, motor impairment
      according to UPDRS motor score was similar at first and second visit. The
      participants had to accomplish a standardized four sentence reading task. The
      acoustical analysis was performed using a standard head-worn microphone for voice
      recordings and commercial audio software (WaveLab). For the determination of
      intonation based upon fundamental frequency (F(0)) variation, we used a computer
      analysis program (Praat). Articulatory velocity was determined by measurement of
      syllable rate and pause ratios. In the PD group, total speech rate (syllables per
      second related to total speech time/TSR) and net speech rate declined from first
      to second examination, especially in the male patients, but showed no significant
      differences to the control group. The course of pitch variation revealed some
      gender particularities. Whereas female patients' pitch variability declined over
      time, male patients' intonation variability remained relatively stable. F(0)
      variation in male and female patients with PD were significantly reduced compared
      with the control group in the first examination and the follow up as well.
      Progression of prosodic impairment over time showed no correlation to disease
      duration or UPDRS motor score. Some aspects of dysprosody in PD show
      characteristic changes over time, but show no clear correlation with general
      motor impairment as assessed by UPDRS motor score. Therefore, we suspect that the
      underlying mechanism could be independent from dopaminergic deficits.

PMID- 19117365
TI  - Restless legs syndrome in multiple sclerosis: a case-control study.
AB  - The aim of our study was to explore restless legs syndrome (RLS) frequency in
      multiple sclerosis (MS)-patients and establish whether RLS could be a symptom of
      MS. Over a period of 1 year, we consecutively enrolled 202 MS-patients and 212
      healthy controls, matched for sex and age, in a case-control study. All of them
      filled in a structured questionnaire according to IRLSSG criteria. Those patients
      who fit the diagnostic criteria were subsequently examined by a neurologist to
      verify the effective presence of RLS. A total of 91 MS-patients (45%) responded
      positively to the questionnaires. The diagnosis of RLS was carried out in 29
      subjects (14.4%). Among the healthy controls, a definite diagnosis of RLS was
      achieved only in 6 subjects (2.8%). The risk of MS patients to present RLS was
      significantly higher (OR.5.76 P:0.00002) than the general population. None of
      them was affected by other medical conditions related to RLS developing. The 62
      remaining patients presented numbness and weakness of the legs not suggestive of
      RLS. Our findings confirm a significant correlation between MS and RLS. In our
      opinion, MS must be definitively included among RLS causes.

PMID- 19117366
TI  - Neuroprotection trials in Parkinson's disease: systematic review.
AB  - Treatments to slow the progression are a major unmet need in Parkinson's disease.
      Detailed assessment of randomized trials testing putative neuroprotective drugs
      was undertaken to inform the design, reporting, and interpretation of future
      studies. This study is a systematic review of trials testing neuroprotective
      drugs. Data were extracted independently by two coauthors. Fifteen completed,
      published trials involving 4,087 participants tested 13 different drugs in 18
      double-blind comparisons with placebo. Seven comparisons involving 2,000 subjects
      assessed MAO-B inhibitors. The primary outcome was change in the Unified
      Parkinson's Disease Rating Scale score in eight trials and time to need for
      dopaminergic therapy in seven. Mean participant age was 62 years, 35% were women,
      the interval from diagnosis to entry averaged 11 months, and the number of
      participants averaged 272 (largest = 806). Follow-up averaged <16 months in all
      but two trials. Detailed randomization methods and success of double-blinding
      were reported in 20% and 13%, respectively. Based on the investigators'
      conclusions, six trials were interpreted as consistent with a neuroprotective
      effect, three as negative, and five as either confounded or not meeting criteria
      for futility. Neuroprotection trials have involved relatively uniform groups of
      participants early in the clinical disease course, with outcomes weighted heavily
      toward motor deterioration. Future trials should include participants with wider
      ranges of disease stages and assess broader neurological outcomes.

PMID- 19117367
TI  - Diffusion-weighted imaging in multiple system atrophy: a comparison between
      clinical subtypes.
AB  - Multiple system atrophy can be classified into two main types, a Parkinsonian
      (MSA-P) and a cerebellar (MSA-C) variant based on clinical presentation. We
      obtained diffusion-weighted magnetic resonance imaging (DWI) in 9 MSA-P and 12
      MSA-C patients and 11 controls, and correlated DWI changes with disease duration
      and severity. We found that Trace (D) values in the entire and anterior putamen
      were significantly higher in MSA-P than in MSA-C patients and controls, whereas
      Trace (D) values in the cerebellum and middle cerebellar peduncle (MCP) were
      significantly higher in MSA-C than in MSA-P patients and controls. Increased
      disease duration was significantly correlated with increased Trace (D) values in
      pons of MSA-P patients, and in cerebellum and MCP of MSA-C patients. Both UMSARS
      and UPDRS motor scores positively correlated with entire and posterior putaminal
      Trace (D) values in MSA-P patients. The diffusivity changes parallel phenotypical
      and pathologic differences between MSA-P and MSA-C patients, suggesting that DWI
      is a feasible tool for in vivo evaluation of neurodegeneration in MSA. Based on
      our findings, Trace (D) measurements in the putamen and pons in MSA-P patients
      and in the cerebellum and MCP in MSA-C patients could serve as quantitative
      markers for microstructural damage in the course of disease.

PMID- 19117368
TI  - Transfer of the shared epitope through microchimerism in women with rheumatoid
      arthritis.
AB  - OBJECTIVE: Rheumatoid arthritis (RA) is an autoimmune disease that affects mostly
      women and is associated with HLA-DRB1 genes having in common a shared epitope
      sequence. In parallel, cells and/or DNA originating from pregnancy
      (microchimerism) persist for decades and could contribute to autoimmunity. The
      aim of this study was to examine whether microchimerism may be a source of the
      shared epitope among women with RA. METHODS: Women with RA and healthy women who
      lacked RA-associated genes such as HLA-DRB1*01 (n=33 and n=46, respectively)
      and/or HLA-DRB1*04 (n=48 and n=64, respectively), were tested for DRB1*01 or
      DRB1*04 microchimerism by HLA-specific quantitative polymerase chain reaction
      assays. As controls, alleles not associated with RA (DQB1*02 and DRB1*15/16) were
      also analyzed. RESULTS: Compared with healthy women, women (42% with RA had a
      higher frequency and higher levels of DRB1*04 microchimerism versus 8%;
      P=0.00002) as well as DRB1*01 microchimerism (30% versus 4%; P=0.0015). Moreover,
      no difference in microchimerism was observed for alleles not associated with RA.
      CONCLUSION: Women with RA had microchimerism with RA-associated HLA alleles, but
      not with non-RA-associated HLA alleles, more often and at higher levels compared
      with healthy women. These observations are the first to indicate that
      microchimerism can contribute to the risk of an autoimmune disease by providing
      HLA susceptibility alleles.

PMID- 19117369
TI  - Parkinson's disease is overdiagnosed clinically at baseline in diagnostically
      uncertain cases: a 3-year European multicenter study with repeat [123I]FP-CIT
      SPECT.
AB  - Overdiagnosis of Parkinson's disease (PD) is suggested by specialist review of
      community diagnosis, and in postmortem studies. In specialist centers 4 to 15% of
      patients entered into clinical trials as early PD do not have functional imaging
      support for a PD diagnosis. In a European multicenter, prospective, longitudinal
      study, we compared clinical diagnosis with functional SPECT imaging using
      [123I]FP-CIT (DaTSCAN, GE Healthcare). Repeat observations were performed over 3
      years in patients with tremor and/or parkinsonism in whom there was initial
      diagnostic uncertainty between degenerative parkinsonism and nondegenerative
      tremor disorders. Video-recording of clinical features was scored independently
      of functional imaging results by two blinded clinicians at 36 months (= gold
      standard clinical diagnosis). Three readers, unaware of the clinical diagnosis,
      classified the images as normal or abnormal by visual inspection. The main
      endpoint was the sensitivity and specificity of SPECT imaging at baseline
      compared with the gold standard. In 99 patients completing the three serial
      assessments, on-site clinical diagnosis overdiagnosed degenerative parkinsonism
      at baseline in diagnostically uncertain cases compared with the gold standard
      clinical diagnosis (at 36 months), the latter giving a sensitivity of 93% and
      specificity of 46%. The corresponding baseline [123I]FP-CIT SPECT results showed
      a mean sensitivity of 78% and a specificity of 97%. Inter-reader agreement for
      rating scans as normal or abnormal was high (Cohen's kappa = 0.94-0.97).

PMID- 19117375
TI  - Chemoattraction and host preference of the gastropod parasitic nematode
      Phasmarhabditis hermaphrodita.
AB  - Phasmarhabditis hermaphrodita is a parasitic nematode that has been formulated
      into a biological control agent for slugs. The nematode responds to slug
      associated cues such as mucus and feces in order to locate potential hosts. We
      assessed the olfactory response of P. hermaphrodita to mucus from 9 species of
      slugs, 2 snails, and 2 earthworms (non-hosts). We then examined the
      susceptibility of each invertebrate test species to high doses of P.
      hermaphrodita to determine whether susceptible species are more attractive than
      non-susceptible species to the nematode. We also studied the numbers of infective
      juveniles produced in each test species, as well as infectivity. Phasmarhabditis
      hermaphrodita showed strong attraction to mucus from the non-susceptible slug
      Arion subfuscus, the snail Helix aspersa, and the highly susceptible slug
      Deroceras reticulatum. In reproduction experiments, P. hermaphrodita produced the
      highest number of infective juveniles in D. reticulatum and Deroceras
      panormitanum; however, there was no significant relationship with attraction.
      Phasmarhabditis hermaphrodita caused significant mortality in 5-11 gastropod
      species tested (and showed no chemotactic preference for susceptible or non
      susceptible species). There was a significant positive relationship between
      numbers of P. hermaphrodita penetrating into non-susceptible species and
      chemotaxis response. These necromenic species represent ideal hosts for P.
      hermaphrodita in terms of providing protection against abiotic and biotic factors
      as well as transport to many diverse areas.

PMID- 19117376
TI  - Screening membrane interactions of pesticides by cells decorated with chromatic
      polymer nanopatches.
AB  - Elucidating the factors contributing to the cell toxicity of pesticides and other
      environmentally sensitive small molecules is critical for evaluation of their
      health impacts and for understanding the biological processes that they affect.
      Disruption and permeation of the plasma membrane, which constitutes the critical
      interface between the cell and its environment, are recognized initiators of
      cytotoxicity. We present a new approach for predicting pesticide cytotoxicity
      through rapid screening of membrane interactions of pesticides using a recently
      developed live-cell chromatic sensor. The sensing platform comprises living
      mammalian cells labeled with polydiacetylene (PDA), a chromatic polymer that
      undergoes intense fluorescence transformations induced by structural
      perturbations of the membrane bilayer. Within a short time after the addition of
      membrane-interacting tested compounds to the labeled cells, the PDA patches emit
      high fluorescence, which can be monitored by conventional spectroscopy and
      microscopy apparatuses. The chromatic technology facilitates rapid evaluation of
      membrane activity of pesticide compounds and is capable of distinguishing between
      toxic effects associated with membrane interactions vs intracellular mechanisms.

PMID- 19117377
TI  - PEGylated and MMP-2 specifically dePEGylated quantum dots: comparative evaluation
      of cellular uptake.
AB  - Polyethylene glycol (PEG)-immobilized quantum dot (QD) nanoparticles, which could
      be specifically dePEGylated in response to the presence of the matrix
      metalloprotease-2 (MMP-2) enzyme, were prepared. The degree of PEGylation (MW
      3400) on the surface of 12 nm streptavidin-coated QDs was stoichiometrically
      controlled by varying the feed amount of a biotin-substrate-PEG conjugate, where
      the substrate contained an MMP-2 cleavable peptide sequence. A biotin-cell
      penetrating peptide (CPP) conjugate was also immobilized onto the surface of the
      PEGylated QD surface to enhance the cellular uptake after dePEGylation. It was
      found that more than nine PEG chains per single QD were required to effectively
      inhibit the cellular uptake of modified QD particles down to around 20%, as
      compared with that of QD without PEG chains. However, the treatment of MMP-2
      enzyme in the medium resulted in a substantial enhancement in the extent of QD
      cellular uptake by dePEGylation with concomitant resurfacing of sterically hidden
      CPP moieties. This study analyzed the effects of surface PEGylation density and
      MMP-2 specific dePEGylation on the cellular uptake of CPP-QD nanoparticles in a
      quantitative manner.

PMID- 19117371
TI  - Origin and evolution of the genetic code: the universal enigma.
AB  - The genetic code is nearly universal, and the arrangement of the codons in the
      standard codon table is highly nonrandom. The three main concepts on the origin
      and evolution of the code are the stereochemical theory, according to which codon
      assignments are dictated by physicochemical affinity between amino acids and the
      cognate codons (anticodons); the coevolution theory, which posits that the code
      structure coevolved with amino acid biosynthesis pathways; and the error
      minimization theory under which selection to minimize the adverse effect of point
      mutations and translation errors was the principal factor of the code's
      evolution. These theories are not mutually exclusive and are also compatible with
      the frozen accident hypothesis, that is, the notion that the standard code might
      have no special properties but was fixed simply because all extant life forms
      share a common ancestor, with subsequent changes to the code, mostly, precluded
      by the deleterious effect of codon reassignment. Mathematical analysis of the
      structure and possible evolutionary trajectories of the code shows that it is
      highly robust to translational misreading but there are numerous more robust
      codes, so the standard code potentially could evolve from a random code via a
      short sequence of codon series reassignments. Thus, much of the evolution that
      led to the standard code could be a combination of frozen accident with selection
      for error minimization although contributions from coevolution of the code with
      metabolic pathways and weak affinities between amino acids and nucleotide
      triplets cannot be ruled out. However, such scenarios for the code evolution are
      based on formal schemes whose relevance to the actual primordial evolution is
      uncertain. A real understanding of the code origin and evolution is likely to be
      attainable only in conjunction with a credible scenario for the evolution of the
      coding principle itself and the translation system.

PMID- 19117378
TI  - Spacer-modulated aggregation of the cyanine dye on the vesicles of gemini
      amphiphiles.
AB  - A series of gemini amphiphiles (bis(2'-heptadecyl-3'-ethylimidazolium)-1,n-alkane
      dibromide, abbreviated as Gn, n = 2, 4, 6, 8, 10) was found to form vesicles
      under ultrasonication in aqueous solution at very low concentration (5 microM),
      which was confirmed by dynamic light scattering (DLS) and transmission electron
      microscopy (TEM). The adsorption and interaction of a cyanine dye (3,3'
      disulfopropyl-4,5,4',5'-dibenzo-9-methyl-thiacarbocyanine triethylammonium salt,
      abbreviated as MTC) on the vesicles was investigated. It was found that the
      cyanine dye could exhibit different colors when interacting with the vesicles.
      The UV-vis spectral measurements revealed the formation of the H or J aggregates
      of the cyanine dye on the vesicles, which is spacer length dependent: the short
      spacer length prefers the formation of the H-aggregate, whereas the longer spacer
      favors the J-aggregate formation. In addition, these aggregates showed different
      absorption positions from those on the planar films. Furthermore, by mixing the
      G2 and G10 vesicles in different ways, the selective aggregation of the cyanine
      dye on the vesicles was realized.

PMID- 19117379
TI  - Electrooxidation of methanol on Pt-modified conductive polymer PEDOT.
AB  - Platinum nanoparticles on a conductive polymer, poly(3,4-ethylenedioxythiophene)
      (PEDOT), exhibit a high catalytic activity for electrooxidation of methanol. Pt
      nanoparticles are prepared by potentiostatic deposition in chloroplatinic acid
      solution at 0.1 V versus standard calomel electrode (SCE) on PEDOT coated carbon
      paper. PEDOT on the substrate facilitates the formation of uniform, well
      dispersed, small clusters of Pt that consist of nanosize particles. The cyclic
      voltammogram of methanol oxidation is characterized by a forward oxidation peak
      current at 0.60 V vs SCE and a backward oxidation peak current at 0.50 V vs SCE.
      The mass specific peak current is found to be as high as 614 mA mg(-1). The
      effects of concentration of H2SO4, mass of Pt, and quantity of PEDOT on mass
      specific activity are studied.

PMID- 19117380
TI  - Counterattack mode differential acetylative deprotection of phenylmethyl ethers:
      applications to solid phase organic reactions.
AB  - A counterattack protocol for differential acetylative cleavage of phenylmethyl
      ether has been developed. The phenylmethyl moiety is liberated as benzyl bromide
      that is isolated and reused providing advantages in terms of waste
      minimization/utilization and atom economy. The applicability of this methodology
      has been extended for solid phase organic reactions with the feasibility of reuse
      of the solid support.

PMID- 19117381
TI  - Phase transitions in the water-hydrogen system at pressures up to 4.7 kbar.
AB  - Using a volumetric technique, a T-P diagram of phase transformations between the
      hydrogen-rich clathrate hydrate (sII phase), hydrogen-filled ice II (C(1) phase),
      and the liquid (L) is studied in the H(2)O-H(2) system at pressures up to 4.7
      kbar and temperatures from -22 to +15 degrees C. The volume and entropy effects
      of these transformations are established in the vicinity of the triple point of
      the L + sII + C(1) equilibrium located at P = 3.6(1) kbar and T = +1(1) degrees
      C. The estimated molar ratios H(2)/H(2)O of phases at the triple point are X(L) =
      0.04(2), X(sII) = 0.32(2), and X(C1) = 0.10(2).

PMID- 19117383
TI  - Atmospheric oxidation mechanism of 1,2-dibromoethane.
AB  - The complete atmospheric oxidation mechanism of 1,2-dibromoethane is proposed.
      There are 32 species and 22 transition state species involved in the proposed
      mechanism. Geometry optimizations and frequency computations are performed using
      the second-order Moller-Plesset perturbation theory and the 6-31G(d) basis set
      for all species and transition states. Single-point energy computations are
      performed using fourth-order Moller-Plesset perturbation theory and coupled
      cluster theory. Potential energy surfaces, including activation energies and
      enthalpies, are determined from the computations. Final products of this
      degradation include OH, CO(2), CO, CH(2)(O), CH(O)CH(O) (glyoxal), bromine
      radicals, CH(O)Br, HOBr, and a reservoir for a new atmospheric compound,
      BrC(O)C(O)Br.

PMID- 19117384
TI  - Efficient peroxide-mediated oxidative refolding of a protein at physiological pH
      and implications for oxidative folding in the endoplasmic reticulum.
AB  - The majority of secreted and outer membrane eukaryotic proteins contain disulfide
      bonds, formed by complex interdependent pathways in the endoplasmic reticulum.
      The current model for the major route of disulfide formation is the regulated
      flow of oxidizing equivalents from molecular oxygen to the membrane-associated
      enzyme Ero1 to protein disulfide isomerase, and hence to substrate proteins. One
      molecule of hydrogen peroxide is produced by Ero1 per disulfide bond made. This
      peroxide is usually considered to be a dangerous by-product. Here we show that
      peroxide, added to a refolding buffer or generated enzymatically in situ, results
      in the efficient refolding of a model protein to the native state. At pH 7.0, the
      kinetics of obtaining the native folded state are more efficient using peroxide
      than by the use of a glutathione redox buffer. Disulfide bond formation by
      peroxide is kinetically favored over oxidation of cysteine to cysteine sulfinic
      acid and over the oxidation of other amino acids in the proteins such as
      methionine. Hence, unless peroxides are added in excess, oxidative damage to the
      folding protein is minimal. Our results offer insights into potential mechanisms
      for disulfide bond formation in vivo.

PMID- 19117385
TI  - Cluster hydration model for binding energy calculations of protein-ligand
      complexes.
AB  - We present a new model for predicting the binding affinity in protein-ligand
      complexes based on an explicit solvent treatment. The model is referred to as the
      cluster hydration model. Test calculations were performed on complexes of FK506
      binding protein (FKBP) and its six ligands. The calculated binding energies had a
      good correlation with experimental binding affinities; the correlation
      coefficient r(2) was 0.93. Moreover, we examined the competition between the
      residue-ligand interactions and the desolvation energies of residues. The results
      suggested that, for the stabilization of the complexes in solution, the
      contributions of nonpolar residues at the binding site are larger than those of
      charged and polar ones because the electrostatic interaction energies between the
      residues and the ligand were mostly canceled by the desolvation penalties.

PMID- 19117386
TI  - Diversity of catalysis by an imido-hydrido complex of molybdenum. Mechanism of
      carbonyl hydrosilylation and silane alcoholysis.
AB  - New Imido hydride complex 1 catalyzes a variety of silylation reactions that
      proceed via initial substrate activation but not silane addition.

PMID- 19117387
TI  - Role of sequence in salt-bridge formation for alkali metal cationized GlyArg and
      ArgGly investigated with IRMPD spectroscopy and theory.
AB  - The roles of hydrogen bonding, electrostatic interactions, sequence, gas-phase
      basicity, and molecular geometry in determining the structures of protonated and
      alkali metal-cationized glycyl-L-arginine (GlyArg) and L-arginylglycine (ArgGly)
      were investigated using infrared multiple photon dissociation spectroscopy in the
      spectral range 900-1800 cm(-1) and theory. The IRMPD spectra clearly indicate
      that GlyArg x M(+), M = Li, Na, and Cs, form similar salt-bridge (SB) structures
      that do not depend significantly on metal ion size. In striking contrast, ArgGly
      x Li(+) exists in a charge-solvated (CS) form, whereas ArgGly x M(+), M = K and
      Cs, form SB structures. SB and CS structures are similarly populated for ArgGly x
      Na(+). Computed energies of low-energy structures are consistent with these
      results deduced from the experimental spectra. By comparison to Arg x M(+),
      GlyArg x M(+) and ArgGly x M(+) have a greater and lesser propensity,
      respectively, to form SB structures. The greater propensity for GlyArg to adopt
      SB structures in complexes with smaller metal cations than for ArgGly is due to
      the ability of alkali metal-cationized GlyArg to adopt a nearly linear
      arrangement of formal charge sites, a structure unfavorable for ArgGly complexes
      due to geometric constraints induced by its different amino acid sequence. The
      amide carbonyl oxygen solvates charge in both the SB and CS form of both
      dipeptides. ArgGly is calculated to be slightly more basic than GlyArg,
      indicating that differences in intrinsic basicity do not play a role in the
      relative SB stabilization of these ions. Loss of a neutral water molecule from
      complexes in which SB structures are most stable indicates that CS structures are
      intermediates in the dissociation pathway, but these intermediates do not
      contribute to the measured IRMPD spectra.

PMID- 19117388
TI  - Borabicyclo[3.3.2]decanes and the stereoselective asymmetric synthesis of 1,3
      diol stereotriads from 1,3-diborylpropenes.
AB  - The synthesis of mixed borabicyclodecane (BBD)-derived 1,3-diborylpropenes (trans
      1) is described. These new bimetallic reagents are effective for the selective
      asymmetric allylboration first of ketones (or ketimines) and second of aldehydes
      (or aldimines). Formed as a thermodynamic mixture of trans regioisomers from cis
      1 through a series of 1,3-borotropic shifts, only trans-1 undergoes the
      monoallylation of ketones. After this single addition, this process is
      effectively shut down after the reaction of the 10-Ph-9-BBD portion in 1. Serving
      as a molecular gate, the rearranged 10-TMS-9-BBD trans-allylborane intermediate
      11 reacts only after an aldehyde (or aldimine) is added. This allylation fixes
      the last two stereogenic centers of the 2-vinyl-1,3-diol stereotriad, ultimately
      resulting in 16 (or 1,3-amino alcohols) in 50-72% yield (>98% ee) as single
      observable diastereomers. These reagents 1 uniquely function as the equivalent of
      1,1-bimetallic allylic reagents, adding sequentially first to ketones and second
      to aldehydes.

PMID- 19117389
TI  - Accurate-mass databases for comprehensive screening of pesticide residues in food
      by fast liquid chromatography time-of-flight mass spectrometry.
AB  - Because of the international trade of fruits and vegetables and the lack of
      harmonized regulations on the use of pesticides worldwide, the development of
      comprehensive screening methods for analyzing hundreds of pesticides and other
      banned chemicals is very convenient. This work reports the development and
      evaluation of a rapid automated screening method for determining pesticide
      residues in food using liquid chromatography electrospray time-of-flight mass
      spectrometry (LC-TOFMS) based on the use of an accurate-mass database. The
      database created includes data not only on the accurate masses of the target ions
      but also the characteristic in-source fragment ions (over 400 fragments included)
      and retention time data. This customized database was associated to commercially
      available software which extracted all the potential compounds of interest from
      the LC-TOFMS raw data of each sample and matched them against the database to
      search for targeted compounds in the sample. This automatic screening method
      requires a careful optimization of the accurate-mass window and retention time
      tolerances, which play a determinant role on the selectivity, accuracy, and
      throughput of the whole procedure. Values of 10 mDa for preliminary screening and
      1 mDa/5 ppm for confirmation along with a +/-0.15 min retention time window were
      found to be optimum for the compounds and samples tested. The optimized methods
      enable the automated screening of ca. 300 compounds in less than 20 min including
      the LC-MS run and data processing. The proposed method was applied to 60 real
      samples, and the results of the positive findings compared well with those
      obtained using a liquid chromatography tandem mass spectrometry (LC-MS/MS) method
      (triple quadrupole). The rates obtained on the identification of compounds in
      spiked and real samples in an automated fashion at different concentration levels
      were over 95% of the compounds, thus revealing as a convenient tool for the large
      scale screening of pesticides in foodstuffs.

PMID- 19117391
TI  - Amperometric oxygen sensor based on a platinum nanoparticle-modified
      polycrystalline boron doped diamond disk electrode.
AB  - Pt nanoparticle (NP)-modified polycrystalline boron-doped diamond (pBDD) disk
      electrodes have been fabricated and employed as amperometric sensors for the
      determination of dissolved oxygen concentration in aqueous solution. pBDD columns
      were cut using laser micromachining techniques and sealed in glass, in order to
      make disk electrodes which were then characterized electrochemically.
      Electrodeposition of Pt onto the diamond electrodes was optimized so as to give
      the maximum oxygen reduction peak current with the lowest background signal. Pt
      NPs, >0-10 nm diameter, were found to deposit randomly across the pBDD electrode,
      with no preference for grain boundaries. The more conductive grains were found to
      promote the formation of smaller nanoparticles at higher density. With the use of
      potential step chronoamperometry, in which the potential was stepped to a
      diffusion-limited value, a four electron oxygen reduction process was found to
      occur at the Pt NP-modified pBDD electrode. Furthermore the chronoamperometric
      response scaled linearly with dissolved oxygen concentration, varied by changing
      the oxygen/nitrogen ratio of gas flowed into solution. The sensor was used to
      detect dissolved oxygen concentrations with high precision over the pH range 4
      10.

PMID- 19117390
TI  - Dynamics of "flap" structures in three HIV-1 protease/inhibitor complexes probed
      by total chemical synthesis and pulse-EPR spectroscopy.
AB  - The unliganded form of nitroxide spin-labeled HIV-1 protease and three different
      complexes with inhibitors were studied by pulse-EPR spectroscopy to determine
      "interflap" distance distributions in solution. In the unliganded enzyme, we
      observed a rather broad distribution with three maxima corresponding to three
      flap conformers; the principal form is a "semiopen/semiopen" conformer. In the
      complexes with inhibitors, the dominant conformer is an asymmetric
      "closed/semiopen" form. Moreover, the distance distribution profile is
      significantly varied among the different inhibitors, which mimic different
      species on the reaction coordinate for enzyme catalyzed proteolysis.

PMID- 19117392
TI  - Electrogenerated chemiluminescence of partially oxidized highly oriented
      pyrolytic graphite surfaces and of graphene oxide nanoparticles.
AB  - Electrogenerated chemiluminescence (ECL) can be obtained from an
      electrochemically oxidized highly oriented pyrolytic graphite electrode or a
      graphene oxide suspension in an aqueous solution containing 0.1 M NaClO(4),
      phosphate buffer (PBS) (pH = 7.0) and 13 mM tri-n-propylamine. Single ECL events
      from individual graphene oxide nanosheets can be observed. The observation of ECL
      in such systems may lead to the development of a new class of carbon-based
      nanomaterials for potentially highly sensitive analytical applications.

PMID- 19117393
TI  - A strategy for synthesis of ionic metal-organic frameworks.
AB  - For the first time, we designed and synthesized a new kind of ionic metal-organic
      framework with lanthanide ions and a carboxyl-functionalized ionic liquid,
      including [Er(4)(mu(3)-OH)(4)(mu(2)-O)(0.5)OL(4)(H(2)O)(3)] x Br(2.90) x Cl(1.10)
      x 2 H(2)O (MOF-1) and [PrL(H(2)O)(4)Cl] x Br x H(2)O(MOF-2).

PMID- 19117395
TI  - Design, synthesis, and biological evaluation of fluorinated analogues of
      salicylihalamide.
AB  - Salicylihalamide A (SA), a benzolactone enamide compound, possesses potent
      cytotoxicity against human tumor cell lines. SA is a selective inhibitor of
      mammalian vacuolar type H(+)-ATPase (V-ATPase), and is distinct from previously
      known V-ATPase inhibitors such as bafilomycins and concanamycins that do not
      discriminate between mammalian and nonmammalian V-ATPases. Because of its potent
      antitumor activity and structural simplicity, SA is a promising candidate for an
      anticancer drug. Although a number of structure-activity relation studies using
      synthetic analogues have been reported, no fluorinated derivative of SA has been
      evaluated even though selective addition of a fluorine atom into a therapeutic
      small molecule candidate often enhances pharmacokinetic and physicochemical
      properties. We designed and synthesized fluorinated analogues of SA and evaluated
      their V-ATPase inhibitory activities. Compared to the natural product, the
      synthetic analogues were potent V-ATPase inhibitors, suggesting that these
      analogues are potential drug candidates and potential molecular probes for mode
      of-action studies using fluorine-based analytical methods such as (19)F-NMR
      spectroscopy.

PMID- 19117394
TI  - Initiation of DNA strand cleavage by 1,2,4-benzotriazine 1,4-dioxide antitumor
      agents: mechanistic insight from studies of 3-methyl-1,2,4-benzotriazine 1,4
      dioxide.
AB  - The antitumor agent 3-amino-1,2,4-benzotriazine 1,4-dioxide (tirapazamine, TPZ,
      1) gains medicinal activity through its ability to selectively damage DNA in the
      hypoxic cells found inside solid tumors. This occurs via one-electron enzymatic
      reduction of TPZ to yield an oxygen-sensitive drug radical (2) that leads to
      oxidatively generated DNA damage under hypoxic conditions. Two possible
      mechanisms have been considered to account for oxidatively generated DNA damage
      by TPZ. First, homolysis of the N-OH bond in 2 may yield the well-known DNA
      damaging agent, hydroxyl radical. Alternatively, it has been suggested that
      elimination of water from 2 generates a benzotriazinyl radical (4) as the
      ultimate DNA-damaging species. In the studies described here, the TPZ analogue 3
      methyl-1,2,4-benzotriazine 1,4-dioxide (5) was employed as a tool to probe the
      mechanism of DNA damage within this new class of antitumor drugs. Initially, it
      was demonstrated that 5 causes redox-activated, hypoxia-selective oxidation of
      DNA and small organic substrates in a manner that is completely analogous to TPZ.
      This suggests that 5 and TPZ damage DNA by the same chemical mechanism.
      Importantly, the methyl substituent in 5 provides a means for assessing whether
      the putative benzotriazinyl intermediate 7 is generated following one-electron
      reduction. Two complementary isotopic labeling experiments provide evidence
      against the formation of the benzotriazinyl radical intermediate. Rather, a
      mechanism involving the release of hydroxyl radical from the activated drug
      radical intermediates can explain the DNA-cleaving properties of this class of
      antitumor drug candidates.

PMID- 19117396
TI  - Direct determination of phosphite in fertilizers by amperometric titration.
AB  - Amperometric titration using two Pt microelectrodes for the determination of
      phosphite in fertilizers based on the oxidation of analyte by iodine is proposed.
      The influence of pH, buffer composition, temperature, and foreign species on the
      end point and titration time was investigated. For titrations carried out at 70
      degrees C using the pH 6.8 phosphate buffer, samples containing ca. 0.4% (m/v)
      P(2)O(5) could be titrated with 0.050 mol L(-1) iodine titrant, and the end point
      determined by extrapolating the linear portions of the plot to their intersection
      coincided with the end point identified by spectrophotometry. Accuracy was
      checked for phosphite determination in five fertilizer samples. Results were in
      agreement at the 95% confidence level (paired t test) with spectrophotometry.
      Recoveries of phosphite added to fertilizer samples ranged from 97% to 102%
      regardless of the amount of spiking in several determinations. The relative
      standard deviation (n = 10) was 1.0% for a diluted sample containing 0.050 mol L(
      1) Na(2)HPO(3).

PMID- 19117397
TI  - Development of an enzyme-linked immunosorbent assay for residue analysis of the
      insecticide emamectin benzoate in agricultural products.
AB  - A direct competitive enzyme-linked immunosorbent assay (dc-ELISA) for the
      analysis of emamectin residues in agricultural products was developed using a
      prepared mouse monoclonal antibody. The working range was 0.3-3.0 ng/mL, and the
      50% inhibition concentration (IC(50)) was 1.0 ng/mL. The assay was sufficiently
      sensitive for analysis of the maximum residue limits in agricultural products in
      Japan (>0.1 microg/g). Emamectin residues contain the following metabolites: the
      4''-epi-amino analogue, the 4''-epi-(N-formyl)amino analogue, the 4''-epi-(N
      formyl-N-methyl)amino analogue, and the 8,9-Z isomer. The dc-ELISA reacted with
      these compounds at ratios of 113, 55, 38, and 9.1% of the IC(50) value of
      emamectin benzoate. Seven kinds of vegetables were spiked with emamectin benzoate
      at concentrations of 15-300 ng/g, and the recoveries were 91-117% in the dc
      ELISA. The dc-ELISA results agreed reasonably well with results obtained by
      liquid chromatography-tandem mass spectrometry (LC-MS/MS) using spiked samples
      and actual (incurred) samples. The results indicate that the dc-ELISA was useful
      for the analysis of emamectin benzoate residues in agricultural products.

PMID- 19117398
TI  - Effects of thermal treatment on the coagulation of soy proteins induced by
      subtilisin Carlsberg.
AB  - The effects of thermal treatment on the subtilisin Carlsberg-induced coagulations
      of soy protein isolate (SPI) and soy proteins in 7S and 11S fractions, most of
      which are beta-conglycinin and glycinin, respectively, were examined by measuring
      the turbidity (OD(660)) of the reaction solutions. With the treatment at 37-60
      degrees C, the turbidity did not increase at all by the proteolysis, while with
      the treatment at 70-96 degrees C, it drastically increased. The degree of the
      coagulation is the highest for the treatment at 80 degrees C and the most
      remarkable for 11S soy protein. Changes in the sodium dodecyl sulfate
      polyacrylamide gel electrophoresis pattern of the digests during the proteolysis
      were in good agreement with those in the turbidities for SPI and 7S and 11S soy
      proteins. Circular dichroism analysis revealed that the amounts of nonstructured
      protein in SPI and 7S and 11S soy proteins were initially 40-50%, increased to 55
      60% by the treatment at 80 degrees C, and further increased to 65-75% by the
      proteolysis. The maximum fluorescence intensity of SPI and 7S and 11S soy
      proteins increased with an increase in the incubation temperature up to 80
      degrees C. These findings suggest that the thermal treatment at 80 degrees C most
      effectively changes the secondary structure of soy proteins and renders them
      coagulate when hydrolyzed by subtilisin Carlsberg.

PMID- 19117400
TI  - Palladium-catalyzed sequential arylation and allylic alkylation of highly
      functionalized ketones: a concise synthesis of mesembrine.
AB  - An unprecedented palladium-catalyzed sequential procedure toward arylation and
      allylic alkylation of highly functionalized cyclohexenones was developed. This
      new protocol leads to useful building blocks containing a benzylic quaternary
      carbon in only one step. A concise total synthesis of mesembrine based on this
      procedure was achieved in only five steps with 22% overall yield.

PMID- 19117399
TI  - Arenamides A-C, cytotoxic NFkappaB inhibitors from the marine actinomycete
      Salinispora arenicola.
AB  - Three new cyclohexadepsipeptides, arenamides A-C (1-3), were isolated from the
      fermentation broth of a marine bacterial strain identified as Salinispora
      arenicola. The planar structures of these compounds were assigned by detailed
      interpretation of NMR and MS/MS spectroscopic data. The absolute configurations
      of the amino acids, and those of the chiral centers on the side chain, were
      established by application of the Marfey and modified Mosher methods. The effect
      of arenamides A and B on NFkappaB activity was studied with stably transfected
      293/NFkappaB-Luc human embryonic kidney cells induced by treatment with tumor
      necrosis factor (TNF). Arenamides A (1) and B (2) blocked TNF-induced activation
      in a dose- and time-dependent manner with IC(50) values of 3.7 and 1.7 microM,
      respectively. In addition, the compounds inhibited nitric oxide (NO) and
      prostaglandin E(2) (PGE(2)) production with lipopolysaccharide (LPS)-induced RAW
      264.7 macrophages. Moderate cytotoxicity was observed with the human colon
      carcinoma cell line HCT-116, but no cytotoxic effect was noted with cultured RAW
      cells. Taken together, these data suggest that the chemoprevention and anti
      inflammatory characteristics of arenamides A and B warrant further investigation.

PMID- 19117401
TI  - Synthesis of 3-hydroxypyridines using ruthenium-catalyzed ring-closing olefin
      metathesis.
AB  - New synthetic routes to substituted 3-hydroxypyridines 6 are presented. Ring
      closing olefin metathesis (RCM)/elimination and RCM/oxidation/deprotection of
      nitrogen-containing dienes 4 are the key processes of the routes. An application
      of RCM/oxidation/deprotection to the synthesis of 3-aminopyridine 13f is also
      described.

PMID- 19117402
TI  - Amyloid-degrading ability of nattokinase from Bacillus subtilis natto.
AB  - More than 20 unrelated proteins can form amyloid fibrils in vivo which are
      related to various diseases, such as Alzheimer's disease, prion disease, and
      systematic amyloidosis. Amyloid fibrils are an ordered protein aggregate with a
      lamellar cross-beta structure. Enhancing amyloid clearance is one of the targets
      of the therapy of these amyloid-related diseases. Although there is debate on
      whether the toxicity is due to amyloids or their precursors, research on the
      degradation of amyloids may help prevent or alleviate these diseases. In this
      study, we explored the amyloid-degrading ability of nattokinase, a fibrinolytic
      subtilisin-like serine protease, and determined the optimal conditions for
      amyloid hydrolysis. This ability is shared by proteinase K and subtilisin
      Carlsberg, but not by trypsin or plasmin.

PMID- 19117403
TI  - In vivo tissue response and degradation behavior of PLLA and stereocomplexed PLA
      nanofibers.
AB  - Biocompatibility of PLLA and stereocomplexed PLA nanofibers was evaluated by
      subcutaneous implantation in rats for 4-12 weeks. Characterization of the
      nanofibers was performed by GPC, SEM, wide-angle X-ray diffraction, and optical
      microscopy of hematoxylin-eosin stained ultrathin sections of explanted
      nanofibers. Stereocomplexed PLA nanofiber showed slower degradation than PLLA
      nanofiber and thus retained their shape after prolonged implantation.
      Furthermore, stereocomplexed PLA nanofiber caused milder inflammatory reaction
      than PLLA nanofiber. These results offer the potential use of PLLA and
      stereocomplexed PLA nanofibers as a biomaterial for short-term and long-term
      tissue regeneration, respectively. Stereocomplexed PLA nanofiber after in vitro
      degradation showed smaller degree of swelling than PLLA nanofiber. Taking the
      results of in vivo degradation together with in vitro degradation into
      consideration, bioabsorption mechanism of the in vivo degradation of the
      nanofibers is proposed.

PMID- 19117404
TI  - New generation of hybrid poly/oligosaccharide nanoparticles as carriers for the
      nasal delivery of macromolecules.
AB  - We have recently reported a new generation of polysaccharide nanoparticles
      consisting of chitosan (CS) and cyclodextrin (CD) derivatives, which exhibit a
      number of advantages when compared to the classical CS nanoparticles. In the
      present work our goal was to explore the potential of these hybrid CS/CD
      nanoparticles as carriers for the nasal delivery of macromolecules. First, we
      evaluated the effect of the amount and type of CD (sulfobutylether-beta-CD or
      carboximethyl-beta-CD) on the physicochemical properties of the nanocarriers.
      Second, we investigated the interaction of CS/CD nanoparticles with the nasal
      epithelium by studying their ability to modulate the tight junctions between
      epithelial cells (Calu-3 cell model) as well as their capacity to overcome
      mucosal barriers (nasal epithelium of rats). Finally, we loaded two selected
      nanocarriers with insulin and studied their potential for enhancing the nasal
      transport of insulin in rabbits. The results showed that CS/CD nanoparticles
      caused a reversible reduction in the transepithelial resistance of the cell
      monolayer, thus increasing the membrane permeability. Moreover, the results
      obtained following the in vivo administration of fluorescent CS/CD nanoparticles
      to rats evidenced their capability to overcome the nasal mucosal barrier.
      Finally, the in vivo evaluation in conscious rabbits revealed that insulin-loaded
      nanoparticles (association efficiencies > 88%) were able to significantly
      decrease plasma glucose levels (more than 35% reduction). Overall, these results
      suggest that these new nanoparticles work as nasal carriers and, therefore, have
      a potential for enhancing the transport of complex molecules across the nasal
      barrier.

PMID- 19117405
TI  - Proteomic profiling identifies aberrant epigenetic modifications induced by
      hepatitis B virus X protein.
AB  - The hepatitis B virus-encoded X (HBx) protein coactivates transcription of a
      variety of viral and cellular genes and it is believed to play essential roles in
      viral replication and hepatocarcinogenesis. To examine the pleiotropic effects of
      HBx protein on host cell protein expression, we utilized 2-DE and MS analysis to
      compare and identify differentially expressed proteins between a stable HBx
      transfected cell line (HepG2-HBx), constitutively expressing HBx, and vector
      control cells. Of the 60 spots identified as differentially expressed (+/- over 2
      fold, p < 0.05) between the two cell lines, 54 spots were positively identified
      by MS/MS analysis. Several recent studies suggested that HBx was involved in
      regional hypermethylation of tumor suppressor genes and global hypomethylation of
      satellite 2 repeats during hepatocarcinogenesis; however, no specific gene has
      been reported as hypomethylated by HBx. Promoter methylation analysis was
      examined for those protein spots showing significant alterations, and our results
      revealed that specific genes, such as aldehyde dehydrogenase 1 (ALDH1), can be
      hypomethylated by HBx, and two calcium ion-binding proteins, S100A6 and S100A4,
      were hypermethylated by HBx and could be re-expressed by AZA (DNA methylase
      inhibitor) treatment. Moreover, via cluster and pathway analysis, we proposed a
      hypothetical model for the HBx regulatory circuit involving aberrant methylation
      of retinol metabolism-related genes and calcium homeostasis-related genes. In
      summary, we profiled proteome alterations between HepG2-HBx and control cells,
      and found that HBx not only induces regional hypermethylation but also specific
      hypomethylation of host cell genes.

PMID- 19117406
TI  - SYBR Green-based real-time PCR assay for detection of VKORC1 and CYP2C9
      polymorphisms that modulate warfarin dose requirement.
AB  - BACKGROUND: Polymorphisms in VKORC1 (vitamin K epoxide reductase complex subunit
      1) and CYP2C9 (cytochrome P450 2C9) genes are considered the major genetic
      factors modulating warfarin dose requirement. As a result, a rapid and economic
      method for genotyping patients for predicting warfarin dose could be useful in
      clinical applications. METHODS: In this study, we developed and validated a
      melting temperature (T(m))-shift genotyping assay for detection of VKORC1 C1173T
      and CYP2C9 A1075C polymorphisms by using SYBR Green-based multiplex allele
      specific PCR and consequent melting curve analysis. In this T(m)-shift genotyping
      assay, a GC-tail was incorporated into one of the two allele-specific primers to
      increase the melting temperature of PCR product, such that both alleles can be
      differentially detected simultaneously at their respective melting curve
      patterns. In total, 100 randomly selected samples of both VKORC1 and CYP2C9 genes
      from each genotype group determined by melting curve were validated by direct DNA
      sequencing and denaturing high-performance liquid chromatography (DHPLC)
      analysis. RESULTS: There was 100% concordance between the results of DNA
      sequencing and T(m)-shift genotyping, and 99% concordance between the results of
      DHPLC assay and T(m)-shift genotyping. CONCLUSIONS: This allele-specific PCR
      assay is convenient, inexpensive and will be useful for VKORC1 and CYP2C9
      genotyping in a clinic laboratory.

PMID- 19117407
TI  - Functional polymorphisms in ACE and CYP11B2 genes and atrial fibrillation in
      patients with hypertensive heart disease.
AB  - BACKGROUND: The activated renin-angiotensin-aldosterone system has been reported
      to play an important role in the pathogenesis of atrial fibrillation (AF). We
      hypothesized that functional genetic variations of angiotensin-converting enzyme
      (ACE) and CYP11B2 genes may influence the susceptibility to AF in patients with
      hypertensive heart disease. METHODS: The I/D polymorphism of ACE was detected by
      polymerase chain reaction (PCR), and the -344C/T polymorphism of the CYP11B2 gene
      was detected using PCR and subsequent cleavage by HaeIII restriction
      endonuclease. RESULTS: The overall distribution of ACE I/D genotypes in patients
      with and without AF was significantly different (p=0.001). The frequency of the
      DD genotype was significantly higher in patients with AF than in patients without
      AF (20.6% vs. 8.1%, OR 2.94, 95% CI 1.64-5.26, p<0.001). The frequency of the D
      allele was significantly higher in the AF group than in the non-AF group
      (p=0.001). After adjustment for age and left atrial dimension, multivariable
      analysis showed that the DD genotype of the ACE gene was an independent risk
      factor for AF in patients with hypertensive heart disease. No relationship
      between -344 C/T CYP11B2 polymorphism and AF was found in this cohort.
      CONCLUSIONS: Our study suggests that ACE I/D polymorphism is associated with AF
      and the DD genotype may be an independent predictive factor for AF in patients
      with hypertensive heart disease.

PMID- 19117408
TI  - Validation for quantification of immunoglobulins by Fourier transform infrared
      spectrometry.
AB  - BACKGROUND: The objective of this study was to develop a robust quantification
      method for simultaneously analyzing molecules in human plasma using the Fourier
      transform infrared (FT-IR) system with a partial least square (PLS) regression.
      METHODS: Plasma spectra were analyzed from 4000 to 500 cm(-1) (with 2.0 cm(-1) of
      resolution and 32 scans), and the molecule concentrations (IgA, IgG, IgM) were
      measured blindly by using a cross-validation model prepared by PLS analysis of
      data from 135 samples. RESULTS: There was a significant correlation between the
      FT-IR predicted concentration and the concentration obtained with the clinical
      reference method: R(2)=0.98 (IgA), R(2)=0.98 (IgG), and R(2)=0.97 (IgM). The root
      mean square error of prediction (RMSEP) was 0.05 g.L(-1) (IgA), 0.4 g.L(-1)
      (IgG), and 0.03 g.L(-1) (IgM). Variability of inter-experimenter reproducibility
      was less than 2%. The interchangeability of the two methods was studied by using
      the Bland-Altman method. CONCLUSIONS: Together with PLS analysis, FT-IR
      spectrometry appears to be an easy-to-use and accurate method to determine
      multianalyte concentrations in dried human plasma. It could be an alternative
      tool for rapidly quantifying many molecules after developing a specific
      predictive model.

PMID- 19117409
TI  - Albumin-based or albumin-linked calibrators cause a positive bias in serum
      proteins assayed by the biuret method.
AB  - BACKGROUND: Assay of total serum protein by the biuret method calibrated with
      albumin standards according to the reference method provides results with a
      positive bias approximately 3%-5% exceeding the total error of 3.4% allowable for
      total protein in serum analysis made by analysers using two-part reagents and
      short-term procedures. METHODS: We used two types of two-part biuret reagents
      utilised in a short-term measurement in analysers with albumin or serum
      calibrators, in which protein was attested by the Kjeldahl method. RESULTS: Tests
      with potentially interfering substances proved that serum blanking used in a
      short-term biuret procedure is not capable of sufficiently eliminating effects of
      serum interferents. A short-term blanking is evidently capable of suppressing
      only an absorbance caused by serum-present coloured and turbid interferents, but
      its capacity to transform them (oxidise, hydrolyse, saponify, etc.) to some other
      not-interfering substances is very low compared with a long-term blanking. Lipids
      and bilirubin are responsible for significant positive bias of total protein in
      normal serum samples (approximately 3%) and even a greater positive offset in
      lipaemic and icteric sera (approximately 5%). We verified that interference tests
      based on a normal serum spiked with endogenous lipids and bilirubin give quite
      false and misleading results in the biuret reaction. A pure albumin, not
      depending on its bovine/human origin, gives absorbance responding only to its
      copper complexes with protein with a biuret regent, while its absorbance with a
      serum also includes the absorbance of interferents present in serum. The simplest
      way to improve current short-term biuret procedures is the use of a human serum
      calibrator with total protein attested by the Kjeldahl method. A serum
      calibrator, behaving analogously to serum samples, compensates for a positive
      bias in most normal sera. Reagents with a greater concentration of active biuret
      components (copper and alkali, reference method included) seem to be
      unnecessarily aggressive to proteins and are responsible for a lower accuracy
      when used in short-term measurements. CONCLUSIONS: Standard Reference Material
      927c based on pure bovine albumin is still recommended and used as the primary
      standard for assays of total protein by colourimetric methods. The albumin
      calibrator is responsible for a positive bias of approximately 3%-5% in serum
      total protein assayed by the biuret reaction both in the reference and in current
      methods. Its substitution by a serum calibrator attested by the Kjeldahl method
      could solve this drawback. Clin Chem Lab Med 2009;47:91-101.

PMID- 19117410
TI  - Falsely elevated carbohydrate antigen 19-9 level due to heterophilic antibody
      interference but not rheumatoid factor: a case report.

PMID- 19117411
TI  - An unusual interference in parathormone assay caused by anti-goat IgG: a case
      report.

PMID- 19117412
TI  - Sublethal concentrations of ammonia impair performance of the teleost fast-start
      escape response.
AB  - The fast-start escape response in fish is essential for predator avoidance, but
      almost nothing is known about whether sublethal concentrations of pollutants can
      impair this reflex. Ammonia, a pervasive pollutant of aquatic habitats, is known
      to have toxic effects on nervous and muscle function in teleost fish. Golden gray
      mullet (Liza aurata L.) were exposed for 24 h to sublethal ammonia concentrations
      in seawater (control, 400 micromol L(-1), or 1,600 micromol L(-1) NH(4)Cl), and
      then their response to startling with a mechanical stimulus was measured with
      high-speed video. Initiation of the escape response was significantly slowed by
      ammonia exposure: response latency rose proportionally from <50 ms in controls to
      >300 ms at a concentration of 1,600 micromol L(-1 ) NH(4)Cl. This indicates toxic
      effects on nervous function within the reflex arc. Impaired escape performance
      was also observed: maximum turning rate, distance covered, velocity, and
      acceleration were significantly reduced by >45% at a concentration of 1,600
      micromol L(-1) NH(4)Cl. This indicates toxic effects on fast-twitch glycolytic
      white muscle function, the muscle type that powers the fast-start response. These
      neuromotor impairments were associated with significant ammonia accumulations in
      venous plasma and white muscle and brain tissue. These results indicate that
      anthropogenic ammonia pollution in aquatic habitats may increase the
      vulnerability of fish to predation, especially by birds and mammals that are not
      affected by water ammonia concentrations.

PMID- 19117413
TI  - Molecular dynamics simulation of the early stages of the synthesis of periodic
      mesoporous silica.
AB  - We present results of detailed atomistic modeling of the early stages of the
      synthesis of periodic mesoporous silica using molecular dynamics. Our simulations
      lead to the proposal of a mechanism that validates several previous experimental
      and modeling studies and answers many controversial issues regarding the
      synthesis of mesoporous silicas. In particular, we show that anionic silicates
      interact very strongly with cationic surfactants and significantly adsorb on the
      surface of micelles, displacing a fraction of previously bound bromide
      counterions. This induces an increase in micelle size and also enhances silica
      condensation at the micelle surface. The presence of larger silica aggregates in
      solution further promotes the growth of micelles and, by binding to surfactant
      molecules in different micelles, their aggregation. This work demonstrates the
      crucial role played by silica in influencing, by way of a cooperative templating
      mechanism, the structure of the eventual liquid-crystal phase, which in turn
      determines the structure of the porous material.

PMID- 19117414
TI  - Tailoring the photoluminescence properties of ionic iridium complexes.
AB  - Density functional theory/time-dependent density functional theory (DFT/TD-DFT)
      calculations were performed to investigate the structural, electronic, and
      optical properties of ionic Ir complexes with several different substituents on
      the cyclometalated ligand. Geometric parameters, highest occupied molecular
      orbital-lowest unoccupied molecular orbital (HOMO-LUMO) energy gap, and Mulliken
      charge on different parts of the molecule were obtained and correlated to the
      calculated emission and absorption energies. We also discuss the influence of the
      position of fluoro-substituent on the spectroscopic properties of Ir complexes.
      As a major trend, the investigated complexes exhibit band shifts that correlate
      with the electron-withdrawing nature of the ligand substituent. Our results also
      show that the lowest emission wavelength is observed at ortho position with
      respect to the coordinating carbon. The different variations observed are
      discussed in terms of emissive states and, more especially, in terms of the
      mixture of ligand-ligand charge-transfer (LLCT) and metal-ligand charge-transfer
      (MLCT) states.

PMID- 19117415
TI  - Structure-activity relationship and studies on the molecular mechanism of
      leishmanicidal N,C-coupled arylisoquinolinium salts.
AB  - Alternative drugs against leishmaniasis are desperately needed. Antimonials, the
      main chemotherapeutic tool, cause serious side effects and promote
      chemoresistance. We previously demonstrated that representatives of N,C-linked
      arylisoquinolines are promising leishmanicidal drug candidates. We now performed
      structure-activity relationship studies varying the aryl portion of our lead
      substrate. The new series of compounds show an enhanced selectivity against
      Leishmania major in comparison to their major host cell, the macrophage. Our
      results suggest that the arylisoquinolinium salts decrease the macrophage
      infection rate acting directly on the intracellular parasites. However, the
      activity of the 4'-i-propyl derivative might also involve the modulation of
      cytokine and nitric oxide production by host macrophages. Additionally, this
      isoquinoline acts synergistically with amphotericin B and does not interact with
      drug-metabolizing cytochrome P450 enzymes involved in the metabolism of
      antileishmanial drugs. The results demonstrate that the newly synthesized
      structurally simplified N,C-coupled arylisoquinolinium salts are promising
      candidates to be considered as leishmanicidal pharmacophores.

PMID- 19117416
TI  - Design, synthesis, and evaluation in vitro of quinoline-8-carboxamides, a new
      class of poly(adenosine-diphosphate-ribose)polymerase-1 (PARP-1) inhibitor.
AB  - Poly(ADP-ribose)polymerase-1 is an important target enzyme in drug design;
      inhibitors have a wide variety of therapeutic activities. A series of quinoline-8
      carboxamides was designed to maintain the required pharmacophore conformation
      through an intramolecular hydrogen bond. 3-Substituted quinoline-8-carboxamides
      were synthesized by Pd-catalyzed couplings (Suzuki, Sonogashira, Stille) to 3
      iodoquinoline-8-carboxamide, an efficient process that introduces diversity in
      the final step. 2-Substituted quinoline-8-carboxamides were prepared by selective
      Pd-catalyzed couplings at the 2-position of 2,8-dibromoquinoline, followed by
      lithium-bromine exchange of the intermediate 2-(alkyl/aryl)-8-bromoquinolines and
      reaction with trimethylsilyl isocyanate. The intramolecular hydrogen bond was
      confirmed by X-ray and by NMR. The SAR of the 3-substituted compounds for
      inhibition of human recombinant PARP-1 activity showed a requirement for a small
      narrow group. Substituents in the 2-position increased potency, with the most
      active 2-methylquinoline-8-carboxamide having IC(50) = 500 nM (IC(50) = 1.8
      microM for 5-aminoisoquinolin-1-one (5-AIQ, a standard water-soluble inhibitor)).

PMID- 19117417
TI  - Synthesis and herbicidal activity of 12-(aryloxyacyloxyimino)-1,15
      pentadecanlactone derivatives.
AB  - A series of novel 12-(aryloxyacyloxyimino)-1,15-pentadecanlactone derivatives (3)
      were synthesized, and their structures including configuration of C=N bond were
      confirmed by (1)H NMR, elemental analysis and X-ray diffraction analysis. The
      bioassay showed that some of them exhibited excellent herbicidal activity against
      Amaranthus tricolor L. The activity of compounds 3 except compounds 3A1-2 was
      much higher than the commercial herbicide 2,4-D and the activity of about half of
      compounds 3 was comparable to the commercial herbicide tribenuron-methyl. The
      further bioassay showed that the representative of compounds 3, 3A1-12, exhibited
      excellent herbicidal activity not only against dicotyledon, such as Amaranthus
      tricolor L., Cucumis sativus L., Glycine max L., and Phaseolus radiatus L., but
      also against monocotyledon, such as Zea mays L. and Oryza sativa L.

PMID- 19117418
TI  - Caffeic acid as antioxidant in fish muscle: mechanism of synergism with
      endogenous ascorbic acid and alpha-tocopherol.
AB  - In an emulsion of corn oil in water with the addition of caffeic acid (Caf-OH)
      and alpha-tocopherol (alpha-TOH), Caf-OH was found to be very active in delaying
      lipid oxidation without affecting significantly the kinetics for alpha-TOH
      degradation. In contrast, Caf-OH addition to fish muscle retarded both the
      degradation of endogenous alpha-TOH and the propagation of lipid oxidation,
      measured by peroxide value (PV) and thiobarbituric acid reactive substances
      (TBARS), with increasing effect with increasing Caf-OH addition (55.5-555.1
      micromol/kg). Electron spin resonance (ESR) spectroscopy confirmed a higher
      capacity of Caf-OH to regenerate alpha-TOH via reduction of the alpha
      tocopheroxyl radical compared to other cinnamic acid derivatives (o-coumaric,
      ferulic, and chlorogenic acids). Degradation of endogenous ascorbate (AscH(-))
      was accelerated at higher concentration of Caf-OH in fish tissue, suggesting a
      role of AscH(-) in the regeneration of Caf-OH. These results indicate that the
      antioxidant mechanism of Caf-OH implies the protection of endogenous alpha-TOH
      localized in tissue membranes where lipid oxidation is initiated and, at the same
      time, Caf-OH regeneration by the endogenous AscH(-). These combined effects
      result in a stronger antioxidant protection against lipid oxidation by favoring,
      as a final point, the protection of alpha-TOH, which is suggested as the last
      defense of fish muscle against lipid oxidation.

PMID- 19117419
TI  - Synthesis of new cationic donor-stabilized phosphenium adducts and their
      unexpected P-substituent exchange reactions.
AB  - The reaction between two 1,3-dialkylimidazolium-2-carboxylates 1a and 1b and two
      different dichlorophosphines (RPCl(2), with R = Ph and NEt(2)) led to new donor
      stabilized phosphenium adducts. When the reaction was performed with the 1,3
      dimethylimidazolium-2-carboxylate 1a and PhPCl(2) in a 2:1 ratio, the phosphine
      4a, bearing two imidazolium moieties, was obtained and led to 5a, after an anion
      exchange reaction with KPF(6), the latter being fully characterized by an X-ray
      structure analysis. In similar conditions, the bis-imidazolium phosphine or
      phosphene-di-ium, 4b, which is analogous to 4a, has been obtained by the addition
      of PhPCl(2) to the 1-dodecyl-3-methylimidazolium-2-carboxylate 1b. However, by
      the use of dichloro(diethylamino)phosphine, (Et(2)N)PCl(2), instead of PhPCl(2),
      the reaction with 1a did not afford the biscationic phosphorus product 6a, an
      analogue to 4a, but, instead, the water-soluble mixed mono-imidazolium
      chlorophosphine 7a. Subsequently, additional kinetic experiments have been
      investigated to rationalize the different reactivities observed with imidazolium
      2-carboxylates and the phosphorus halide derivatives. We, thus, found that the
      bis-imidazolium phosphine 4b was very rapidly formed in the above-mentioned
      reaction and was slowly converted, thereafter, back to the mixed mono-imidazolium
      chlorophosphine 8b in the presence of the residual starting dichlorophosphine.
      Additionally, the addition of PhPCl(2) to the phosphene-di-ium 4b represents, to
      our knowledge, the first example of a P-substituent exchange reaction involving a
      P-C bond formation in imidazolium phosphines. On the other hand, the air
      stability and the solubility of these new cationic functional phosphines in
      different media render such ligands very appealing in coordination chemistry for
      catalysis in mono- or biphasic media.

PMID- 19117420
TI  - Isolation and structural characterization of a binuclear intermediate species
      pertinent to transmetalation of Zn(salphen) complexes and the formation of
      polynuclear salen structures.
AB  - Zinc(II) salphen complexes equipped with additional alkoxy donor groups at the 3
      position of the salicylideneimine groups have been prepared to bind metal
      acetates in a second coordination sphere close to the central Zn(II) ion. The
      isolated binuclear monosalphen complexes have been studied in detail using NMR
      and MS techniques. Further synthesis has revealed that the formation of binuclear
      species from the parent salphen ligands is dependent on the nature of the
      bridging group between the two salicylideneimine groups and is prevented by
      replacement of one of the alkoxy substituents for a bulky t-Bu group. One of the
      binuclear Zn2 complexes was crystallographically characterized and can be
      regarded as a structural model for the intermediate stage of the transmetalation
      of the central Zn(II) center within these dinuclear compounds by other metal
      acetate salts. Furthermore, the X-ray diffraction structure also relates well
      with some intermediate structural stages of the buildup of various polynuclear
      salen structures.

PMID- 19117421
TI  - Self-assembly of a series of cobalt(II) coordination polymers constructed from
      H2tbip and dipyridyl-based ligands.
AB  - A series of interesting Co(II)-H(2)tbip coordination polymers incorporating
      different auxiliary ligands, {[Co(tbip)(bipy)(H(2)O)(3)] x 0.5(bipy) x H(2)O}(n)
      (1), [Co(tbip)(bipy)](n) (2), {[Co(3)(tbip)(3)(dpe)(3)] x 0.5(dpe) x 3 H(2)O}(n)
      (3), [Co(2)(tbip)(2)(dpe)(H(2)O)](n) (4), [Co(2)(tbip)(2)(bpa)(H(2)O)](n) (5),
      and {[Co(2)(tbip)(2)(bpa)(2)] x 2.5 H(2)O}(n) (6) (H(2)tbip = 5-tert-butyl
      isophthalic acid; bipy = 4,4'-bipyridine; dpe = 1,2-di (4-pyridyl)ethylene; bpa =
      1,2-bi(4-pyridyl)ethane) were synthesized. X-ray structural analyses of 1-6
      reveal a diverse range of structures, ranging from 1D (1) to 2D (2, 6) to 3D (3,
      4, 5). Complex 1 shows 1D zigzag bipy-bridged polymeric chains with the terminal
      tbip ligands as pendants, which are extended to a 3D hydrogen-bonded
      supramolecular framework involving 1D open channels which encapsulate guest bipy
      molecules. Polymers 2 and 6 feature similar 2D infinite layer frameworks
      consisting of cobalt dimers. The structure of 3 is constructed from
      [Co(2)(tbip)(2)](n) layers, which consists of alternating left- and right-handed
      helical chains, and further pillared by dpe ligands into a 3D six-connected self
      penetrating 4(8).6(6).8 network. The prominent cavities in 3 are parallel to the
      (101) plane and encapsulate free dpe as guest molecules. Polymers 4 and 5 are
      isostructural, showing 2-fold interpenetrating 3D alpha-Po networks constructed
      from binuclear cobalt nodes. The thermal stabilities and X-ray powder diffraction
      studies indicate that the framework of 3 can keep stable after the loss of guest
      molecules. Studies of the magnetic susceptibilities of 2-6 reveal weak
      antiferromagnetic exchange interactions between adjacent Co(II) centers.

PMID- 19117422
TI  - Findings of the challenge to predict aqueous solubility.

PMID- 19117423
TI  - Synthesis of novel 4,6-di(substituted)amino-1,2-dihydro-1,3,5-triazine
      derivatives as topical antiseptic agents.
AB  - A series of novel 4,6-di(substituted)amino-1,2-dihydro-1,3,5-triazine derivatives
      designed to have ClogP of 5.1-7.5 was synthesized and evaluated for their
      antiseptic properties by MIC and MBC tests against Gram-positive and Gram
      negative bacteria, including MRSA, VRE, and P. aeruginosa. Among these compounds,
      4-alkyl-6-aralkyl derivatives having ClogP of 6.6-7.1 and 4-alkyl-6-aryl or 4,6
      dialkyl derivatives with ClogP of 6.0-6.4 showed pronounced antibacterial
      activities in both tests.

PMID- 19117424
TI  - Emergence and maintenance of nutrient limitation over multiple timescales in
      terrestrial ecosystems.
AB  - Nutrient availability often limits primary production, yet the processes
      governing the dynamics of nutrient limitation are poorly understood. In
      particular, plant-available (e.g., nitrate) versus plant-unavailable (e.g.,
      dissolved organic nitrogen) nutrient losses may have qualitatively different
      impacts on nutrient limitation. We examine processes controlling equilibrium and
      transient nutrient dynamics at three separate timescales in a model of a nutrient
      cycling through plants and soil. When the only losses are from the plant
      available nutrient pool, nutrient limitation at a long-term equilibrium is
      impossible under a wide class of conditions. However, plant biomass will appear
      to level off on a timescale controlled by plant nutrient turnover (years in
      grasslands, decades to centuries in forests), even though it can grow slowly
      forever. Primary production can be nutrient limited in the long-term when there
      are losses of plant-unavailable nutrients or when the mineralization flux
      saturates with increasing detrital mass. The long timescale required for soil
      nutrient buildup is set by the plant-unavailable loss rate (centuries to
      millennia). The short timescale (hours to days) at which available nutrients in
      the soil equilibrate in the model is controlled by biotic uptake. These insights
      into processes controlling different timescales in terrestrial ecosystems can
      help guide empirical and experimental studies.

PMID- 19117425
TI  - Is storage an adaptation to spatial variation in resource availability?
AB  - When individuals store resources acquired while moving through a spatially
      variable habitat, a form of population structure arises. The theoretical
      consequences of this process for resource competition are studied for
      phytoplankton species consuming a single nutrient resource, using a Lagrangian
      modeling approach. Each competitor population is divided into many subpopulations
      that move through two model habitats with gradients in nutrient availability: an
      unstirred chemostat and a partially mixed water column. The results provide
      little indication that resource storage contributes to competitive fitness in the
      scenarios analyzed. Superior competitors usually reduce the limiting nutrient to
      low concentrations at steady state or sometimes have high maximal growth rates.
      Resource storage enhances competitive fitness in temporally variable habitats
      where encounters with rich nutrient pulses are strongly periodic. However, in
      purely spatially variable habitats where encounters with rich nutrient patches
      are random, resource storage does not appear to provide much benefit, at least
      for passively moving organisms that cannot control their location.

PMID- 19117426
TI  - Visualizing solution-phase reaction dynamics with time-resolved X-ray
      liquidography.
AB  - Most chemical reactions occur in solution, and complex interactions between
      solute and solvent influence the rich chemistry of these processes. To track time
      dependent processes in such reactions, researchers often use time-resolved
      spectroscopy. In these experiments, an optical pulse (pump) initiates a reaction,
      and another time-delayed optical pulse (probe) monitors the progress of the
      reaction. However, because of the wavelength range of the probe light used in
      these experiments, from infrared to ultraviolet, researchers cannot directly
      determine detailed structural information such as the bond lengths and bond
      angles of reaction intermediates. In addition, not all intermediates might be
      sensitive to the spectroscopic signal chosen for the experiment. This Account
      describes time-resolved X-ray liquidography (TRXL), a technique that overcomes
      these problems. In this technique, we replace the optical probe with the
      diffraction of hard X-ray pulses emitted from a synchrotron source. In TRXL,
      diffraction signals are sensitive to all chemical species simultaneously. In
      addition, each chemical species has a characteristic diffraction signal, a
      fingerprint, that we calculate from its three-dimensional atomic coordinates.
      Because, X-rays scatter from all atoms in the solution sample, including both the
      solute and the solvent, the analysis of TRXL data can track not only the reaction
      pathways of the solute molecules but also the solvent behavior and the solute
      solvent arrangement, thus providing a global picture of the reactions. We have
      used TRXL to study structural dynamics and spatiotemporal kinetics of many
      molecular systems including diatomic molecules, haloalkanes, organometallic
      complexes, and protein molecules over timescales from picoseconds to
      milliseconds. We have observed that TRXL data adds to and, in some cases,
      contradicts results from time-resolved spectroscopy. For example, TRXL has shown
      that the reaction intermediates upon C-I bond dissociation in C(2)H(4)I(2) and
      C(2)F(4)I(2) have completely different structures and corresponding subsequent
      reaction pathways, underscoring the dramatic effect of the fluorine substitution.
      We have also used TRXL to identify a new reaction intermediate of the photolysis
      of Ru(3)(CO)(12) that has no bridging carbonyl groups. Though not detected by
      time-resolved infrared spectroscopy, this intermediate predominates based on the
      TRXL data. In looking at the quaternary conformational changes of hemoglobin,
      TRXL analysis suggests a faster transition than was suggested by optical
      spectroscopy. The time resolution of TRXL is currently limited by the X-ray pulse
      width available from synchrotron sources ( approximately 100 ps). The resolution
      should improve to 100 fs or better with X-ray free electron lasers. With this
      higher resolution, real time observation of ultrafast chemical events such as
      bond-breaking and bond-making will be possible.

PMID- 19117428
TI  - The PREP Act: liability protection for medical countermeasure development,
      distribution, and administration.

PMID- 19117429
TI  - Biosafety laboratories.

PMID- 19117430
TI  - Are Londoners prepared for an emergency? A longitudinal study following the
      London bombings.
AB  - The UK government sees increasing individual preparedness as a priority, but the
      level of preparedness of people in the UK for a large-scale emergency is not
      known. The London bombings of July 7, 2005, affected many Londoners and may have
      altered their sense of vulnerability to a future terrorist attack. We used a
      longitudinal study design to assess individual preparedness within the same
      sample of Londoners at 2 points in time: immediately after the bombings (T(1))
      and 7 to 8 months later (T(2)). A demographically representative sample of 1,010
      Londoners participated in a phone interview at T(1). Subsequently, at T(2), 574
      of the same people participated in a follow-up phone interview. At T(1) 51% of
      Londoners had made 4 or more relevant emergency plans; 48% had gathered 4 or more
      relevant supplies in case of emergency. There was evidence of increased
      preparedness at T(2), by which time 90% had made 4 or more emergency plans.
      Ethnicity, low social status, and having felt a sense of threat during the
      bombings predicted increased preparedness between T(1) and T(2). Women in
      general, and women of low social status in particular, perceived themselves to be
      unprepared in the event of a future terrorist attack. In summary, Londoners show
      moderate levels of emergency preparedness, which increased following the London
      bombings. Although we cannot know whether this association is causal, the
      prospective nature of the study increases the likelihood that it is. However,
      preparedness is still patchy, and there are important demographic associations
      with levels of preparedness and perception of vulnerability. These findings have
      implications for future development of individual and community emergency
      preparedness policy.

PMID- 19117431
TI  - The anthrax vaccine and research: reactions from postal workers and public health
      professionals.
AB  - During the 2001 anthrax attacks, public health agencies faced operational and
      communication decisions about the use of antibiotic prophylaxis and the anthrax
      vaccine with affected groups, including postal workers. This communication
      occurred within an evolving situation with incomplete and uncertain data.
      Guidelines for prophylactic antibiotics changed several times, contributing to
      confusion and mistrust. At the end of 60 days of taking antibiotics, people were
      offered an additional 40 days' supply of antibiotics, with or without the anthrax
      vaccine, the former constituting an investigational new drug protocol. Using data
      from interviews and focus groups with 65 postal workers in 3 sites and structured
      interviews with 16 public health professionals, this article examines the
      challenges for public health professionals who were responsible for communication
      with postal workers about the vaccine. Multiple factors affected the response,
      including a lack of trust, risk perception, disagreement about the
      recommendation, and the controversy over the military's use of the vaccine. Some
      postal workers reacted with suspicion to the vaccine offer, believing that they
      were the subjects of research, and some African American workers specifically
      drew an analogy to the Tuskegee syphilis study. The consent forms required for
      the protocol heightened mistrust. Postal workers also had complex and ambivalent
      responses to additional research on their health. The anthrax attacks present us
      with an opportunity to understand the challenges of communication in the context
      of uncertain science and suggest key strategies that may improve communications
      about vaccines and other drugs authorized for experimental use in future public
      health emergencies.

PMID- 19117432
TI  - Pandemic influenza and acute care centers: taking care of sick patients in a
      nonhospital setting.
AB  - The ongoing spread of H5N1 avian influenza in Southeast Asia has raised concern
      about a worldwide influenza pandemic and has made clear the need to plan in
      advance for such an event. The federal government has stressed the importance of
      planning and, in particular, has asked hospitals and public health agencies to
      develop plans to care for patients outside of traditional healthcare settings.
      These alternative or acute care centers (ACCs) would be opened when hospitals,
      emergency departments (EDs), and clinics are overwhelmed by an influenza
      pandemic. The University of Michigan Hospital System (UMHS), a large tertiary
      care center in southeast Michigan, has been developing a model for offsite care
      of patients during an influenza pandemic. This article summarizes our planning
      efforts and the lessons learned from 2 functional exercises over the past 3
      years.

PMID- 19117433
TI  - Emergency preparedness training for veterinarians: prevention of zoonotic
      transmission.
AB  - Natural zoonotic outbreaks can cause widespread devastation, and several zoonoses
      can be transmitted as agents of bioterrorism. Although veterinarians can be vital
      in controlling the transmission of zoonotic diseases, many lack knowledge about
      their roles in emergency response and about zoonoses. A training session titled
      "Prevention of Zoonotic Disease Transmission" was provided for New York
      veterinarians. The training was evaluated using pre-training, post-training, and
      follow-up surveys, which measured increase in and retention of knowledge. Seventy
      five (75) veterinary professionals participated in the training, and 91%
      responded on pre- and post-training surveys. The percentage of respondents who
      correctly answered the objective knowledge questions increased from pre-training
      to post-training. Furthermore, follow-up surveys demonstrated that participants
      were able to retain much of the information from the training session. Very
      little research has been found that evaluates a similar training event. As
      knowledge increases, additional training conferences could benefit veterinarians
      and supplement this research. The results of the pre-training, post-training, and
      follow-up surveys indicate that veterinary professionals' knowledge of zoonoses
      can be significantly improved after receiving training; participants found the
      training to be useful and requested additional training, indicating that
      veterinary professionals have a desire to learn about emergency preparedness
      topics.

PMID- 19117434
TI  - What role can alternative care facilities play in an influenza pandemic?

PMID- 19117435
TI  - Medical reserve corps: engaging volunteers in public health preparedness and
      response.

PMID- 19117438
TI  - Smectic C to cubic phase transition of 4'-n-docosyloxy-3'-nitrobiphenyl-4
      carboxylic acid (ANBC-22) and alternating-current electric field effect.
AB  - Smectic C (SmC) to cubic (Cub) phase transition behavior of 4'-n-docosyloxy-3'
      nitrobiphenyl-4-carboxylic acid (ANBC-22) and alternating-current (AC) electric
      field effect on the SmC phase were examined. The most important and unexpected
      finding is that even at a temperature 8 K below the zero-field SmC to Cub phase
      transition temperature (T(SmC-Cub) approximately 408 K) determined previously for
      the compound and without field, the Cub phase growth occurs, after a very long
      induction period of several hours. The X-ray diffraction measurements revealed
      the formation of an Im3m-type Cub phase at the temperature. It is suggested that
      the "true" transition temperature, which is difficult to determine precisely,
      exists around 396 K. The time-dependence of the Cub phase growth both without
      field and under field was analyzed using the well-known Avrami equation, implying
      the nucleation and growth mechanism mainly operating in the SmC to Cub phase
      transformation. The fact uncovered is that between 408 and 396 K, the SmC to Cub
      transformation is virtually prohibited by the strongly limited nucleation. It is
      concluded that the effect of the electric field on the transition is to promote
      the nucleation of the Cub phase in the temperature region where the Cub phase is
      potentially more stable than the precursory SmC phase.

PMID- 19117444
TI  - Hydrophoretic sorting of micrometer and submicrometer particles using anisotropic
      microfluidic obstacles.
AB  - We describe a hydrophoretic device that uses rotational flows induced by
      regularly patterned obstacles only on the top wall for preparing samples of
      biological particles, including micrometer and submicrometer particles, and DNA
      molecules. Many of the current continuous separation devices based on physical
      fields are limited to the separation of cells and micrometer-sized particles due
      to their dependence on a particle volume, and the purely hydrodynamic separation
      of macromolecules such as DNA or protein complexes remains a challenge.
      Hydrophoresis is entirely based on hydrodynamics using rotational flows induced
      by anisotropic obstacles. Different sizes of micrometer and submicrometer beads,
      as well as DNA molecules, were separated into distinct trajectories using two
      kinds of hindrance mechanisms. Continuous separation of these particles was
      achieved using the obstacles, demonstrating the potential of hydrophoresis for
      biological sample preparation on the micro- and nanoscales, with the advantages
      of continuous flow and sheathless passive operation.

PMID- 19117445
TI  - Analysis of the interface and its position in C60(n+) secondary ion mass
      spectrometry depth profiling.
AB  - C60(n+) ions have been shown to be extremely successful for SIMS depth profiling
      of a wide range of organic materials, causing significantly less degradation of
      the molecular information than more traditional primary ions. This work focuses
      on examining the definition of the interface in a C60(n+) SIMS depth profile for
      an organic overlayer on a wafer substrate. First it investigates the optimum
      method to define the organic/inorganic interface position. Variations of up to 8
      nm in the interface position can arise from different definitions of the
      interface position in the samples investigated here. Second, it looks into the
      reasons behind large interfacial widths, i.e., poor depth resolution, seen in
      C60(n+) depth profiling. This work confirms that, for Irganox 1010 deposited on a
      wafer, the depth resolution at the Irganox 1010/substrate interface is directly
      correlated to the roughening of material. C60n+

PMID- 19117446
TI  - Electrostatic interaction based approach to thrombin detection by surface
      enhanced Raman spectroscopy.
AB  - We have developed an electrostatic interaction based biosensor for thrombin
      detection using surface-enhanced Raman spectroscopy (SERS). This method utilized
      the electrostatic interaction between capture (thrombin aptamer) and probe
      (crystal violet, CV) molecules. The specific interaction between thrombin and
      aptamer could weaken the electrostatic barrier effect from the negative charged
      aptamer SAMs to the diffusion process of the positively charged CV from the bulk
      solution to the Au nanoparticle surface. Therefore, the more the bound thrombin,
      the more the CV molecules near the Au nanoparticle surface and the stronger the
      observed Raman signal of CV, provided the Raman detections were set at the same
      time point for each case. This procedure presented a highly specific selectivity
      and a linear detection of thrombin in the range from 0.1 nM to 10 nM with a
      detection limit of about 20 pM and realized the thrombin detection in human blood
      serum solution directly. The electrostatic interaction based technique provides
      an easy and fast-responding optical platform for a "signal-on" detection of
      proteins, which might be applicable for the real time assay of proteins.

PMID- 19117447
TI  - Profiling of endogenous serum phosphorylated peptides by titanium (IV)
      immobilized mesoporous silica particles enrichment and MALDI-TOFMS detection.
AB  - Phosphorylation is one of the most important post-translational modifications of
      proteins, which modulates a wide range of biological functions and activities of
      proteins. The phosphorylation of proteins is also associated with the pathway of
      cancer cells. We have previously enriched the low molecular weight proteome from
      human plasma based on the combination of size exclusion and adsorption mechanism
      by using highly ordered mesoporous silica particles. Herein, highly ordered
      mesoporous silica particles were modified with titanium phosphonate to
      selectively capture the phosphopeptides from complex peptide and protein
      mixtures. The limit of detection for phosphopeptides from beta-casein and
      standard phosphopeptide spiked in human serum was as low as 1.25 fmol based on
      MALDI-TOFMS detection. The modified mesoporous silica particles were further used
      to enrich phosphopeptides from serum of hepatocellular carcinoma patients and
      healthy individuals and then analyzed with MALDI-TOFMS. The combination of
      isobaric tagging for relative and absolute quantitation labeling with MALDI
      TOFMS/MS was further applied to validate the serum phosphopeptide profiling
      result of MALDI-TOFMS. The profiling of the serum phosphopeptides between the
      cancer patients and healthy persons was distinguishingly different, which
      indicated the potential ability of this technique for cancer diagnosis and
      biomarker discovery. The approach developed here would be applicable to other
      biological samples and a wide variety of diseases.

PMID- 19117449
TI  - Cyclic voltammograms at coplanar and shallow recessed microdisk electrode arrays:
      guidelines for design and experiment.
AB  - Although microdisk electrode arrays (MEAs) have been extensively used for more
      than three decades, the existing rules do not provide an unambiguous formula for
      the calculation of the minimum interelectrode distance (d) necessary for steady
      state current response. With the aim of formulating generally applicable
      guidelines for design and experiment with MEAs, cyclic voltammograms were
      simulated for coplanar and shallow recessed microdisk electrode arrays with
      various interelectrode distances and dimensionless scan rates (V). The
      dimensionless scan rate (V) is a function of the radius (a) of the individual
      electrodes in the array, the diffusion coefficient (D) of the analyte, and the
      potential scan rate (v). The cyclic voltammograms at microdisk electrode arrays
      are grouped into five categories corresponding to the contributions of linear and
      radial diffusion to the overall responses. These categories are illustrated in a
      zone diagram based on the effect of V and d on the shape of cyclic voltammograms.
      The zone diagram reveals the minimum d and a cluster of linked d and V values
      that are incident to sigmoidal wave responses. For shallow recessed microdisk
      electrode arrays, the zones representing hemispherical diffusion are larger than
      that for coplanar arrays. The minimum d necessary for hemispherical diffusion
      becomes smaller as recess depth increases. With the zone diagram, one can predict
      the type of the cyclic voltammograms that can be expected for different
      microelectrode array geometries and experimental conditions. The fitting between
      simulation and experimental data validates our conclusions.

PMID- 19117448
TI  - Mass spectrometric determination of disulfide linkages in recombinant therapeutic
      proteins using online LC-MS with electron-transfer dissociation.
AB  - In the biotechnology industry, the generation of incorrectly folded recombinant
      proteins, either from an E.coli expression system or from an overexpressed CHO
      cell line (disulfide scrambling), is often a great concern as such incorrectly
      folded forms may not be completely removed in the final product. Thus,
      significant efforts have been devoted to map disulfide bonds to ensure drug
      quality. Similar to ECD, disulfide bond cleavages are preferred over peptide
      backbone fragmentation in ETD. Thus, an online LC-MS strategy combining collision
      induced dissociation (CID-MS(2)), electron-transfer dissociation (ETD-MS(2)), and
      CID of an isolated product ion derived from ETD (MS(3)) has been used to
      characterize disulfide-linked peptides. Disulfide-linked peptide ions were
      identified by CID and ETD fragmentation, and the disulfide-dissociated (or
      partially dissociated) peptide ions were characterized in the subsequent MS(3)
      step. The online LC-MS approach is successfully demonstrated in the
      characterization of disulfide linkages of recombinant human growth hormone
      (Nutropin), a therapeutic monoclonal antibody, and tissue plasminogen activator
      (Activase). The characterization of disulfide-dissociated or partially
      dissociated peptide ions in the MS(3) step is important to assign the disulfide
      linkages, particularly, for intertwined disulfide bridges and the unexpected
      disulfide scrambling of tissue plasminogen activator. The disulfide-dissociated
      peptide ions are shown to be obtained either directly from the ETD fragmentation
      of the precursors (disulfide-linked peptide ions) or indirectly from the charge
      reduced species in the ETD fragmentation of the precursors. The simultaneous
      observation of disulfide-linked and disulfide-dissociated peptide ions with high
      abundance not only provided facile interpretation with high confidence but also
      simplified the conventional approach for determination of disulfide linkages,
      which often requires two separate experiments (with and without chemical
      reduction). The online LC-MS with ETD methodology represents a powerful approach
      to aid in the characterization of the correct folding of therapeutic proteins.

PMID- 19117450
TI  - Bioanalysis without sample cleanup or chromatography: the evaluation and initial
      implementation of direct analysis in real time ionization mass spectrometry for
      the quantification of drugs in biological matrixes.
AB  - Two key bottlenecks in pharmaceutical bioanalysis are sample cleanup and
      chromatographic separations. Although multiple approaches have been developed in
      the past decade to either shorten or multiplex these steps, they remain the rate
      limiting steps as ADME (Absorption, Distribution, Metabolism, and Excretion)
      property screening is being routinely incorporated into the drug discovery
      process. In this work, a novel system incorporating an automated Direct Analysis
      in Real Time (DART) ionization source coupled with a triple-quadrupole mass
      spectrometer has been developed and evaluated for quantitative bioanalysis. This
      system has the capability of directly analyzing samples from their biological
      matrixes and therefore potentially eliminating the need for sample cleanup and
      chromatographic separations. A LEAP Technologies autosampler was customized to
      perform the automated sample introduction into the DART beam with high precision,
      which significantly improved the reproducibility of the method. Additional
      pumping was applied to the atmospheric pressure inlet on the mass spectrometer to
      compensate for the increased vacuum load because of the use of high-flow helium
      by the DART. This resulted in an improvement of detection sensitivity by a factor
      of 10 to 100 times. Matrix effects for a diversified class of compounds were
      evaluated directly from untreated raw plasma and were found to range from
      approximately 0.05 to 0.7. Precision and accuracy were also tested for multiple
      test compounds over a dynamic range of four orders of magnitude. The system has
      been used to analyze biological samples from both in vivo pharmacokinetic studies
      and in vitro microsomal/S9 stability studies, and the results generated were
      similar to those obtained with conventional LC/MS/MS methods. Overall, this new
      automated DART-triple quadrupole mass spectrometer system has demonstrated
      significant potential for high-throughput bioanalysis.

PMID- 19117451
TI  - Unlocking interpretation in near infrared multivariate calibrations by orthogonal
      partial least squares.
AB  - Near infrared spectroscopy (NIR) was developed primarily for applications such as
      the quantitative determination of nutrients in the agricultural and food
      industries. Examples include the determination of water, protein, and fat within
      complex samples such as grain and milk. Because of its useful properties, NIR
      analysis has spread to other areas such as chemistry and pharmaceutical
      production. NIR spectra consist of infrared overtones and combinations thereof,
      making interpretation of the results complicated. It can be very difficult to
      assign peaks to known constituents in the sample. Thus, multivariate analysis
      (MVA) has been crucial in translating spectral data into information, mainly for
      predictive purposes. Orthogonal partial least squares (OPLS), a new MVA method,
      has prediction and modeling properties similar to those of other MVA techniques,
      e.g., partial least squares (PLS), a method with a long history of use for the
      analysis of NIR data. OPLS provides an intrinsic algorithmic improvement for the
      interpretation of NIR data. In this report, four sets of NIR data were analyzed
      to demonstrate the improved interpretation provided by OPLS. The first two sets
      included simulated data to demonstrate the overall principles; the third set
      comprised a statistically replicated design of experiments (DoE), to demonstrate
      how instrumental difference could be accurately visualized and correctly
      attributed to Wood's anomaly phenomena; the fourth set was chosen to challenge
      the MVA by using data relating to powder mixing, a crucial step in the
      pharmaceutical industry prior to tabletting. Improved interpretation by OPLS was
      demonstrated for all four examples, as compared to alternative MVA approaches. It
      is expected that OPLS will be used mostly in applications where improved
      interpretation is crucial; one such area is process analytical technology (PAT).
      PAT involves fewer independent samples, i.e., batches, than would be associated
      with agricultural applications; in addition, the Food and Drug Administration
      (FDA) demands "process understanding" in PAT. Both these issues make OPLS the
      ideal tool for a multitude of NIR calibrations. In conclusion, OPLS leads to
      better interpretation of spectrometry data (e.g., NIR) and improved understanding
      facilitates cross-scientific communication. Such improved knowledge will decrease
      risk, with respect to both accuracy and precision, when using NIR for PAT
      applications.

PMID- 19117452
TI  - Single drop microextraction using commercial capillary electrophoresis
      instruments.
AB  - Single drop microextraction (SDME), a simple and efficient sample
      preconcentration method for capillary electrophoresis (CE), was performed using
      two different commercial CE instruments. With a CE instrument providing
      adjustable forward and backward pressures, a single drop of an aqueous acceptor
      phase covered with a thin layer of an organic phase was formed at the capillary
      tip by programming the sample-handling functions of the instrument to perform 3
      phase SDME where the organic film is essentially a membrane. Analytes from an
      acidic donor phase were concentrated into a basic acceptor phase yielding 190
      fold enrichment in 10 min. When the donor phase was agitated using a
      microstirrer, a 2000-fold enrichment was obtained in 10 min. For a less flexible
      CE instrument, 2-phase SDME was carried out with a large volume pentanol drop
      held by a Teflon sleeve, yielding 110-fold enrichments in 30 min. We demonstrate
      a practical and automated SDME-CE technique with accuracy and reproducibility
      that is easy to practice to attain matrix isolation and high concentration
      sensitivity.

PMID- 19117453
TI  - Conjugated polyelectrolyte based real-time fluorescence assay for adenylate
      kinase.
AB  - Addition of adenosine 5'-triphosphate (ATP) to a solution of the anionic
      conjugated polyelectrolyte PPECO2 and copper(II) ion (Cu2+) recovers the Cu2+
      quenched fluorescence of PPECO(2) to a significantly greater extent compared with
      the addition of adenosine 5'-diphosphate (ADP) or adenosine 5'-monophosphate
      (AMP) at the same concentration levels. Taking advantage of the differential
      response of the PPECO2-Cu2+ system to ATP, ADP and AMP, we have developed
      fluorescence turn-off and turn-on assays that monitor the catalytic activity of
      adenylate kinase (ADK) in the equilibrium transphosphorylation reaction (ATP +
      AMP <--> 2ADP). The fluorescence turn-on and turn-off assays monitor the forward
      and reverse transphosphorylation reactions, respectively. The forward assay
      operates with ATP substrate present at the submillimolar concentration range and
      offers a straightforward and rapid detection of ADK catalytic activity with the
      enzyme present in the nanomolar range, in either end-point or real-time formats.
      The real-time fluorescence intensity from PPECO2 can be converted to substrate
      (ATP) concentration in the forward reaction assay by using an ex-situ calibration
      curve, allowing ADK catalyzed reaction rates and kinetic parameters to be
      determined. ADK activation by Mg2+ and inhibition by Ag+ and product are analyzed
      using the optimized assay system. Non-specific interactions are observed between
      the assay complex and other proteins, but the signal response to the ADK assay is
      demonstrated to mainly arise from the specific enzyme catalyzed
      transphosphorylation reaction.

PMID- 19117454
TI  - Characterization of phosphorylated peptides using traveling wave-based and drift
      cell ion mobility mass spectrometry.
AB  - Phosphorylation is one the most studied and important post translational
      modifications. Nano electrospray mass spectrometry coupled with traveling wave (T
      Wave)-based ion mobility has been used to filter for phosphorylated peptides in
      tryptic protein digests. T-Wave parameters have been optimized to maximize the
      separation between phosphorylated and non-phosphorylated peptides. A method to
      calibrate the T-Wave device, to provide estimates of collision cross sections, is
      presented, and these estimates are in excellent agreement with values obtained on
      drift cell instrumentation. Phosphorylated peptides have smaller cross sections
      which enables their separation from non-phosphorylated peptides of the same m/z.
      Post-mobility fragmentation is used to obtain the primary sequence for peptides
      of interest. This approach is shown to have potential as an additional screen for
      phosphorylated peptides, where up to 40% of observed peptides can be eliminated
      from the study.

PMID- 19117455
TI  - Barometric sensitive coatings based upon osmium complexes dissolved in a
      fluoroacrylic polymer.
AB  - Pressure sensitive paints (PSP) that measure the changes in air pressure have
      proved to be useful in the design of aircraft and other vehicles. In this study
      we incorporate highly luminescent divalent osmium complexes into PSP. The
      divalent osmium complexes were heptafluorobutyrate salts of [Os(N-N)2(L-L)]2+ or
      [Os(L-L)2(N-N)]2+, where N-N is a derivative of 1,10-phenanthroline, and L-L is a
      diphosphine or diarsine ligand. The complexes were dissolved into
      poly(1,1,1,3,3,3-hexafluoroisopropylmethacrylate-co-1H,1H
      dihydroperflurobutylmethacrylate) (FIB) at a concentration of 0.002 g of complex
      to 1.000 g of polymer. The luminescence of the coatings was tested for pressure
      sensitivity, temperature dependence, and photodegradation. The paints featured
      strong pressure response, and the temperature dependence of the luminescence was
      measured as low as -0.11% degrees C(-1). Several of the complexes exhibited
      little photodegradation upon prolonged exposure to 400 nm light. These attributes
      make the complexes very desirable luminescent dyes for PSP.

PMID- 19117456
TI  - Dynamic biochemical information recovery in spontaneous human seminal fluid
      reactions via 1H NMR kinetic statistical total correlation spectroscopy.
AB  - Human seminal fluid (HSF) is a complex mixture of reacting glandular metabolite
      and protein secretions that provides critical support functions in fertilization.
      We have employed 600-MHz (1)H NMR spectroscopy to compare and contrast the
      temporal biochemical and biophysical changes in HSF from infertile men with
      spinal cord injury compared to age-matched controls. We have developed new
      approaches to data analysis and visualization to facilitate the interpretation of
      the results, including the first application of the recently published K-STOCSY
      concept to a biofluid, enhancing the extraction of information on biochemically
      related metabolites and assignment of resonances from the major seminal protein,
      semenogelin. Principal components analysis was also applied to evaluate the
      extent to which macromolecules influence the overall variation in the metabolic
      data set. The K-STOCSY concept was utilized further to determine the
      relationships between reaction rates and metabolite levels, revealing that
      choline, N-acetylglucosamine, and uridine are associated with higher peptidase
      activity. The novel approach adopted here has the potential to capture dynamic
      information in any complex mixture of reacting chemicals including other
      biofluids or cell extracts.

PMID- 19117457
TI  - In situ analysis of a bimodal size distribution of superparamagnetic
      nanoparticles.
AB  - The dispersed iron oxide nanoparticles of ferrofluids in aqueous solution are
      difficult to characterize due to their protective polymer coatings. We report on
      the bimodal size distribution of superparamagnetic iron oxide nanoparticles found
      in the MRI contrast agent Resovist, which is a representative example of
      commercial nanoparticle-based pharmaceutical formulations. The radii of the
      majority of the nanoparticles (>99%) range from 4 to 13 nm (less than 1% of the
      particles display radii up to 21 nm). The maxima of the size distributions are at
      5.0 and 9.9 nm. The analysis was performed with in situ characterization of
      Resovist via online coupling of asymmetrical flow field-flow fractionation (A4F)
      with small-angle X-ray scattering (SAXS) using a standard copper X-ray tube as a
      radiation source. The outlet of the A4F was directly coupled to a flow capillary
      on the SAXS instrument. SAXS curves of nanoparticle fractions were recorded at 1
      min time intervals. We recommend using the A4F-SAXS coupling as a routine method
      for analysis of dispersed nanoparticles with sizes in the range of 1-100 nm. It
      allows a fast and quantitative comparison of different batches without the need
      for sample preparation.

PMID- 19117458
TI  - Newborn screening of inborn errors of metabolism by capillary electrophoresis
      electrospray ionization-mass spectrometry: a second-tier method with improved
      specificity and sensitivity.
AB  - The advent of electrospray-ionization mass spectrometry (ESI-MS) has given rise
      to expanded newborn screening programs for the early detection of inborn errors
      of metabolism (IEM). Despite the benefit of high-throughput screening for disease
      prognosis, conventional ESI-MS methods are limited by inadequate specificity,
      complicated sample handling, and low positive predictive outcome that can
      contribute to a high rate of false-positives. Herein, we report a robust strategy
      for neonatal screening based on capillary electrophoresis-electrospray ionization
      mass spectrometry (CE-ESI-MS) that offers a convenient platform for the direct
      analysis of amino acids, acylcarnitines, and their stereoisomers from dried blood
      spot (DBS) extracts without chemical derivatization. On-line sample
      preconcentration with desalting by CE-ESI-MS allowed for improved concentration
      sensitivity when detecting poorly responsive metabolites in complex biological
      samples without ionization suppression or isomeric/isobaric interferences. Method
      validation demonstrated that accurate yet precise quantification can be achieved
      for 20 different amino acid and acylcarnitine biomarkers associated with IEMs
      when using a single non-deuterated internal standard. CE-ESI-MS represents a
      promising second-tier method in newborn screening programs that is compatible
      with ESI-MS/MS technology in cases when improved specificity and sensitivity is
      warranted for diagnosis confirmation and subsequent monitoring.

PMID- 19117459
TI  - Simulations and experimental investigation of atmospheric transport in an ambient
      metastable-induced chemical ionization source.
AB  - Since its inception, Direct Analysis in Real Time (DART) has seen utility in a
      wide range of applications including chemical reaction monitoring, pharmaceutical
      screening, and forensic mass spectrometry. Despite the growing interest in DART
      applications, there has been limited research into the fundamental physiochemical
      phenomena affecting sampling, ionization, and atmospheric ion transport.
      Presented here are the first experimentally validated finite element method
      simulations of an ambient DART-type metastable-induced chemical ionization
      source. It was found that complex coupled fluid dynamics, heat transfer, and
      electrostatic phenomena within the sampling region determine the variability in
      ion transmission efficiencies affecting the overall sensitivity of analysis.
      Particle tracing plots of a circular acetaminophen tablet placed in various
      positions and orientations yielded insight into optimal sample placement and
      evidence for sweet spots conducive to better ion transport. Experiments in a wide
      range of electric field conditions were performed, finding that under optimum
      sample placement, sensitivity could be improved by as much as 128% if ion
      mobility contributions were minimized.

PMID- 19117460
TI  - Digital microfluidic method for protein extraction by precipitation.
AB  - We present the first microfluidic method for extracting proteins from
      heterogeneous fluids by precipitation. The new method comprises an automated
      protocol for precipitation of proteins onto surfaces, rinsing the precipitates to
      remove impurities, and resolubilization in buffer for further analysis. The
      method is compatible with proteins representing a range of different
      physicochemical properties, as well as with complex mixtures such as fetal bovine
      serum and cell lysate. In all cases, the quantitative performance (measured using
      a fluorescent assay for % recovery) was comparable to that of conventional
      techniques, which are manual and require more time. Thus, this work represents an
      important first step in efforts to develop fully automated microfluidic methods
      for proteomic analyses.

PMID- 19117461
TI  - Biotin-avidin binding kinetics measured by single-molecule imaging.
AB  - The high affinity of avidin for biotin has made it useful for many bioanalytical
      applications involving the immobilization of proteins, vesicles, and other
      biomolecules to surfaces. To understand the formation and stability of the
      resulting biotin-avidin complex, it is useful to know the kinetics of the binding
      reaction, especially for situations where the complex is formed at a liquid-solid
      interface typically used in sensor or separation applications. In this work, a
      single-molecule fluorescence method is developed for measuring the kinetics and
      affinity constant for the binding of neutravidin, a deglycosylated variant of
      avidin, to surface-immobilized biotin. Biotin was immobilized using succinimidyl
      ester chemistry onto amine sites on glass surfaces. The surface density of biotin
      was controlled by the extreme dilution of 3-aminopropyltriethoxysilane into a
      monolayer of 2-cyanoethyltriethoxysilane. The resulting biotin binding sites are
      spaced apart by micrometer distances, and this avoids crowding effects and makes
      the resolution of single molecules possible. The binding and unbinding of
      individual tetramethylrhodamine-labeled neutravidin molecules is measured in situ
      by total-internal-reflection fluorescence (TIRF) microscopy imaging. Single
      molecule detection and counting is readily achieved by this measurement, where
      quantitative control is established by determining the probabilities of false
      positive and negative events based on the intensity distributions of background
      and single-molecule spots and by comparing the bound molecule populations with
      the independently measured density of binding sites on the surface. The kinetics
      of binding and unbinding are evaluated by intermittent imaging and counting the
      number of bound neutravidin molecules versus time, following introduction of a
      neutravidin solution or its replacement by buffer over the low-density
      biotinylated surface. The neutravidin binding kinetics were found to be fast,
      essentially diffusion-controlled, while the stability of the complex and its
      dissociation rate appear to be influenced by the chemistry of biotin
      immobilization.

PMID- 19117462
TI  - Anticancer drug-DNA interactions measured using a photoinduced electron-transfer
      mechanism based on luminescent quantum dots.
AB  - A sensing system based on the photoinduced electron transfer of quantum dots
      (QDs) was designed to measure the interaction of anticancer drug and DNA, taking
      mitoxantrone (MTX) as a model drug. MTX adsorbed on the surface of QDs can quench
      the photoluminescence (PL) of QDs through the photoinduced electron-transfer
      process; and then the addition of DNA will bring the restoration of QDs PL
      intensity, as DNA can bind with MTX and remove it from QDs. Sensitive detection
      of MTX with the detection limit of 10 nmol L(-1) and a linear detection range
      from 10 nmol L(-1) to 4.5 micromol L(-1) was achieved. The dependence of PL
      intensity on DNA amount was successfully utilized to investigate the interactions
      between MTX and DNA. Both the binding constants and the sizes of binding site of
      MTX-DNA interactions were calculated based on the equations deduced for the PL
      recovery process. The binding constant obtained in our experiment was generally
      consistent with previous reports. The sensitive and speedy detection of MTX as
      well as the avoidance of modification or immobilization process made this system
      suitable and promising in the drug-DNA interaction studies.

PMID- 19117463
TI  - Combined charged residue-field emission model of macromolecular electrospray
      ionization.
AB  - The mechanism of the multiple charging of macromolecules in electrospray
      ionization (ESI) continues to inspire debate and controversy. Recently, we
      proposed that the number of charges on a macromolecule is determined by the
      emission of small charge carriers from macromolecule-containing nanodroplets and
      that, after solvent evaporation, the remaining charge is transferred to the
      macromolecule. In this study, we tested the applicability of this new theory for
      macromolecular, positive-ion ESI mass spectrometry by measuring the mean charge
      states and charge distributions of globular proteins under non-denaturing and
      denaturing conditions. Predictions of protein mean charge states for native state
      proteins are in excellent agreement with mass spectrometric measurements, giving
      strong credence to the proposed theory. Theoretical predictions are also in good
      agreement with mean charge states measured for proteins in basic solutions (pH =
      11.5). For some proteins in acidic solutions (pH = 2.1), the measured mean charge
      states are anomalously higher than the Rayleigh limit of a water droplet with a
      volume equivalent to that of the protein. We propose that some macromolecules
      that are highly charged in solution may desorb from charged droplets of the same
      polarity in a similar manner to that whereby charge carriers emit from
      nanodroplets, leading to "supercharged" macromolecular ions. Examination of rate
      expressions for solvent evaporation and charge-carrier emission demonstrates that
      the newly proposed model for ESI is consistent with previously reported ion
      emission kinetics. Overall, we obtained additional experimental evidence for the
      charge carrier emission model for macromolecular charging, suggesting
      opportunities for understanding and applying ESI-MS.

PMID- 19117464
TI  - Absolute peptide quantification by lutetium labeling and nanoHPLC-ICPMS with
      isotope dilution analysis.
AB  - The need of analytical methods for absolute quantitative protein analysis spurred
      research on new developments in recent years. In this work, a novel approach was
      developed for accurate absolute peptide quantification based on metal labeling
      with lutetium diethylenetriamine pentaacetic acid (Lu-DTPA) and nanoflow high
      performance liquid chromatography-inductively coupled plasma isotope dilution
      mass spectrometry (nanoHPLC-ICP-IDMS). In a two-step procedure peptides were
      derivatized at amino groups with diethylenetriamine pentaacetic anhydride (DTPAA)
      followed by chelation of lutetium. Electrospray ionization mass spectrometry (ESI
      MS) of the reaction product demonstrated highly specific peptide labeling. Under
      optimized nanoHPLC conditions the labeled peptides were baseline-separated, and
      the excess labeling reagent did not interfere. A 176Lu-labeled spike was
      continuously added to the column effluent for quantification by ICP-IDMS. The
      recovery of a Lu-DTPA-labeled standard peptide was close to 100% indicating high
      labeling efficiency and accurate absolute quantification. The precision of the
      entire method was 4.9%. The detection limit for Lu-DTPA-tagged peptides was 179
      amol demonstrating that lutetium-specific peptide quantification was by 4 orders
      of magnitude more sensitive than detection by natural sulfur atoms present in
      cysteine or methionine residues. Furthermore, the application to peptides in
      insulin tryptic digest allowed the identification of interfering reagents
      decreasing the labeling efficiency. An additional advantage of this novel
      approach is the analysis of peptides, which do not naturally feature ICPMS
      detectable elements.

PMID- 19117465
TI  - Water as an in situ NMR indicator for impurity acids in ionic liquids.
AB  - A sensitive in situ NMR spectroscopic method for detecting acids contaminating
      ionic liquids (ILs) has been developed. The chemical shift and the spectral width
      of water added to ILs were used as indicators to measure the impurity acid level.
      Owing to the high resolution power of NMR, the detection limit is below the level
      of 10(-3) mol kg(-1). A new method is applicable to a number of commonly used ILs
      such as the imidazolium- and ammonium-based ILs except for those composed of
      acidic cations or anions. The method was utilized to monitor the purification
      efficiency in the recrystallization of a typical hydrophilic IL, 1-butyl-3
      methylimidazolium methanesulfonate from acetone. It was demonstrated that
      impurity acids can be almost perfectly removed by single or double
      recrystallization.

PMID- 19117466
TI  - Carbon nanotube-ionic liquid composite sensors and biosensors.
AB  - A new composite electrode has been fabricated using multiwall carbon nanotubes
      (MWCNT) and the ionic liquid n-octylpyridinum hexafluorophosphate (OPFP). This
      electrode shows very attractive electrochemical performances compared to other
      conventional electrodes using graphite and mineral oil, notably improved
      sensitivity and stability. One major advantage of this electrode compared to
      other electrodes using carbon nanotubes and other ionic liquids is its extremely
      low capacitance and background currents. A 10% (w/w) loading of MWCNT was
      selected as the optimal composition based on voltammetric results, as well as the
      stability of the background response in solution. The new composite electrode
      showed good activity toward hydrogen peroxide and NADH, with the possibility of
      fabricating a sensitive biosensor for glucose and alcohol using glucose oxidase
      and alcohol dehydrogenase, respectively, by simply incorporating the specific
      enzyme within the composite matrix. The marked electrode stability and
      antifouling features toward NADH oxidation was much higher for this composite
      compared to a bare glassy carbon electrode. While a loading of 2% MWCNT showed
      very poor electrochemical behavior, a large enhancement was observed upon gentle
      heating to 70 degrees C, which gave a response similar to the optimum composition
      of 10%. The ease of preparation, low background current, high sensitivity,
      stability, and small loading of nanotubes using this composite can create new
      novel avenues and applications for fabricating robust sensors and biosensors for
      many important species.

PMID- 19117467
TI  - Probing the ionic atmosphere of single-stranded DNA using continuous flow
      capillary electrophoresis and fluorescence correlation spectroscopy.
AB  - Two-beam fluorescence cross-correlation spectroscopy coupled with continuous flow
      capillary electrophoresis (2bFCCS-CFCE) was used to study the relationship
      between diffusion and effective charge of a fluorescently labeled 40-base
      polythymine single-stranded DNA (ssDNA) as a function of Mg2+ concentration.
      Cross-correlation analysis of the fluorescence monitored from two spatially
      offset microscopic detection volumes revealed the diffusion and electrophoretic
      migration of ssDNA at a range of Mg2+ concentrations and electric field
      strengths. The effective charge of the ssDNA could then be determined using
      simple calculations. It was found that as the Mg2+ concentration in the buffer
      solution increased, the diffusion of the ssDNA also increased, while the
      effective charge of the ssDNA decreased. This was believed to be caused by
      increased association of the Mg2+ counterions with the negatively charged
      backbone of the ssDNA, which partially neutralized the negatively charged
      functional groups and allowed the ssDNA to adopt a more compact structure. To our
      knowledge, this is the first demonstration of the measurement of effective charge
      of ssDNA in relation to Mg2+ concentration.

PMID- 19117468
TI  - Screening of biomineralization using microfluidics.
AB  - Biomineralization is the process where biological systems produce well-defined
      composite structures such as shell, teeth, and bones. Currently, there is
      substantial momentum to investigate the processes implicated in biomineralization
      and to unravel the complex roles of proteins in the control of polymorph
      switching. An understanding of these processes may have wide-ranging significance
      in health care applications and in the development of advanced materials. We have
      demonstrated a microfluidic approach toward these challenges. A reversibly sealed
      T-junction microfluidic device was fabricated to investigate the influence of
      extrapallial (EP) fluid proteins in polymorph control of crystal formation in
      mollusk shells. A range of conditions were investigated on chip, allowing fast
      screening of various combinations of ion, pH, and protein concentrations. The
      dynamic formation of crystals was monitored on chip and combined with in situ
      Raman to reveal the polymorph in real time. To this end, we have demonstrated the
      unique advantages of this integrated approach in understanding the processes
      involved in biomineralization and revealing information that is impossible to
      obtain using traditional methods.

PMID- 19117469
TI  - Evaluation of ultrafast 2D NMR for quantitative analysis.
AB  - Recent ultrafast methods make it possible to obtain two-dimensional (2D) nuclear
      magnetic resonance (NMR) spectra in a fraction of a second. This paper presents
      the first evaluation of ultrafast 2D NMR for quantitative analysis. On the basis
      of optimized conditions presented in recent studies, two homonuclear ultrafast
      techniques, J-resolved spectroscopy and TOCSY, are evaluated on model mixtures in
      terms of repeatability, long time stability, and linearity. The results are
      compared to conventional 1D (1)H NMR spectroscopy. Repeatabilities better than 1%
      for ultrafast J-resolved spectra and better than 7% for TOCSY spectra are
      obtained. The long-term stability is better than 4% for J-resolved spectroscopy
      and between 2% and 11% for TOCSY. Moreover, both methods are characterized by
      excellent linearities. This new analytical method opens important perspectives
      for fast, precise, and accurate quantitative analysis of complex mixtures and for
      the quantitative study of short time scale phenomena.

PMID- 19117470
TI  - Highly specific enrichment of glycopeptides using boronic acid-functionalized
      mesoporous silica.
AB  - A novel boronic acid functionalized mesoporous silica, which holds the attractive
      features of high surface area and large accessible porosity, was developed to
      enrich glycopeptides. This is the first time that mesoporous material has been
      introduced into glycoproteome. In comparison to direct (traditional) analysis,
      this novel method enabled 2 orders of magnitude improvement in the detection
      limit of glycopeptides. The unbiased nature of organo-boronic acid groups also
      made this method applicable to all kinds of glycopeptides regardless of their
      sizes, structures, and hydrophilicities.

PMID- 19117471
TI  - Plasma yolk precursor dynamics during egg production by female greater scaup
      (Aythya marila): Characterization and indices of reproductive state.
AB  - We characterized dynamics of the plasma yolk precursors vitellogenin (VTG), very
      low-density lipoprotein (total VLDL-TG), and VLDL particle size distribution
      during egg production by female greater scaup (order: Anseriformes, Aythya
      marila). We also evaluated VTG and total VLDL-TG as physiological indices of
      reproductive state. Mean (+/-1 SE) plasma concentrations of VTG and total VLDL-TG
      for females with nondeveloped ovaries were 0.58 +/- 0.05 microg Zn mL(-1) and
      3.75 +/- 0.29 mmol TG L(-1), respectively. Yolk precursor concentrations
      increased rapidly to maximum levels in association with small increases in ovary
      mass during rapid follicle growth. Mean concentrations of VTG and total VLDL-TG
      for females with a full ovarian follicle hierarchy were 3.38 +/- 0.40 microg Zn
      mL(-1) and 7.31 +/- 2.56 mmol TG L(-1), respectively. Concentrations of VTG and
      total VLDL remained elevated throughout the laying cycle and decreased markedly
      by 3 d into incubation. Individual reproductive state (non-egg producing vs. egg
      producing) was more accurately identified by plasma profiles of VTG (90%) than by
      those of total VLDL-TG (74%). Greater scaup VLDL particle sizes during egg
      production were within the range for predicted yolk-targeted VLDL size (25-44
      nm). We conclude that plasma profiles of VTG and total VLDL-TG can be used as
      nonlethal, physiological indices of reproductive state in greater scaup and
      should be of great utility to a variety of evolutionary, ecological, and applied
      conservation studies of reproduction in waterfowl.

PMID- 19117472
TI  - Does competition allow male mate choosiness in threespine sticklebacks?
AB  - The theory of mate choice posits that intensified competition for mates can
      generate variation in either the strength or the direction of mate preferences
      within the competing sex. Here, we show that intensified male competition,
      manipulated through the operational sex ratio, induced differential mate
      choosiness among threespine stickleback males Gasterosteus aculeatus. In the
      absence of male competition, males were choosy independent of their condition
      when presented sequentially with a large and a small female. However, in a male
      biased social setting, males in poor condition became indiscriminate, whereas
      good-condition males continued to be selective. Hence, competition induced
      condition-dependent mate choosiness. This was probably due to mating
      opportunities decreasing more for poor-condition than for good-condition males
      when competition intensified, resulting in condition-dependent cost of choice.
      Variation in condition and cost of choice could thus allow the persistence of
      male mate choosiness in populations experiencing intense male competition.

PMID- 19117473
TI  - Organic supernanostructures self-assembled via solution process for explosive
      detection.
AB  - Three different polymorphic crystalline structures, including microbelts and
      flowerlike supernanostructures, were obtained via a simple solution process by
      utilizing different solvents from an oligoarene derivative. Explosive
      chemosensors based on these self-assembled organic crystalline nanostructures
      were successfully fabricated. The differences in the structures on the
      microscopic level and in the film morphologies led to dramatic enhancements of
      the explosive detection speed. With the evolution of structures from the netted
      1D microbelts to the flowerlike supernanostructures, the detection speed of the
      chemosensors for DNT and TNT was improved by more than 700 times. Our discovery
      demonstrates that the morphology control through self-assembly provides a new
      platform to utilize organic crystalline microstructures for chemosensors,
      optoelectronics, biosensors and bioelectronics, and so forth.

PMID- 19117474
TI  - IR spectroscopic testing of surfaces in water ice and in icy mixtures with
      prussic acid or ammonia.
AB  - An experimental technique is developed for spectral studies of ice films
      deposited at 77 K onto the ZnSe inner windows of a cell, so that the spectra
      could be registered in the presence of gaseous adsorbate. Pure H2O or D2O ice as
      well as HCN/D2O and ND3/D2O mixed icy films with different dopant/water ratios
      (1:10, 1:5, and 1:1) were investigated. The surface area of ice deposited at 77 K
      H2O estimated from adsorption measurements was about 160 m2/g. Bands of dangling
      hydroxyl groups disappear on raising the temperature up to 130-160 K when the
      changes of bulk absorption provide evidence for a phase transition from amorphous
      to polycrystalline ice. Surface properties of icy films were characterized by low
      temperature adsorption of CO and CHF3. Insertion of small doses of HCN or ammonia
      does not change the acid/base strength of dangling hydroxyl groups or
      coordinately unsaturated surface oxygen atoms, but it changes the proportion
      between the concentrations of these sites as compared with pure water ice. For
      high dopant concentrations, the dangling hydroxyls were not observed, and the
      dominant adsorption sites for CO are likely to be the unsaturated oxygen atoms,
      while serious structural changes occur in the bulk of ices.

PMID- 19117475
TI  - Solid-state NMR studies of aminocarboxylic salt bridges in L-lysine modified
      cellulose.
AB  - LysCel is a cellulose-based material in which l-lysine molecules are grafted with
      their amino side chains to the cellulose hydroxyl groups. This modification
      increases considerably the mechanical strength and resistance of cellulosic
      structures toward water. It has been attributed to the formation of double salt
      bridges between lysine aminocarboxyl groups in the zwitterionic state. In order
      to characterize this unusual structure, we have performed high-resolution solid
      state (15)N and (13)C CPMAS NMR experiments on LysCel samples labeled with (15)N
      in the alpha-position or epsilon-position. Furthermore, (13)C-(15)N REDOR
      experiments were performed on LysCel where half of the aminocarboxyl groups were
      labeled in 1-position with 13C and the other half in alpha-position with (15)N.
      The comparison with the 13C and 15N chemical shifts of l-leucine lyophilized at
      different pH shows that the aminocarboxyl groups of LysCel are indeed
      zwitterionic. The REDOR experiments indicate distances of about 3.5 A between the
      carboxyl carbon and the nitrogen atoms of different aminocarboxyl groups,
      indicating that the latter are in close contact with each other. However, the
      data are not compatible with isolated aminocarboxyl dimers but indicate the
      assembly of zwitterionic aminocarboxyl dimers either in a flat ribbon or as
      tetramers, exhibiting similar intra- and interdimer (13)C...(15)N distances. This
      interaction of several aminocarboxyl groups is responsible for the zwitterionic
      state, in contrast to the gas phase, where amino acid dimers exhibiting two OHN
      hydrogen bonds are neutral.

PMID- 19117476
TI  - Highly efficient and highly enantioselective asymmetric hydrogenation of ketones
      with TunesPhos/1,2-diamine-ruthenium(II) complexes.
AB  - The TunePhos/diamine-Ru(II) complex combined with t-BuOK in 2-propanol
      effectively catalyzes enantioselective hydrogenation of a wide range of simple
      ketones including aromatic, heteroaromatic, alpha,beta-unsaturated, and
      cyclopropyl ketones, affording high reactivity (up to 1,000,000 TON) and
      excellent enantioselectivities (>99% ee for 13 examples).

PMID- 19117477
TI  - Efficient biosensor interfaces based on space-controlled self-assembled
      monolayers.
AB  - In this paper we demonstrate control over the spacing of surface-modifying probe
      molecules through the use of labile dendron spacers. During this process, anchor
      molecules are first adsorbed to a surface, with dendron modifiers attached.
      Steric interactions of the bulky dendrons control the density of anchor molecules
      bound to the surface. The dendron branches are subsequently detached from the
      anchor molecules, and the anchors are chemically modified with probe molecules,
      resulting in a surface with controlled spacing between probe molecules. Control
      over this spacing is important when the probe size is small in comparison with
      the target molecule. This importance is demonstrated for the binding of protein
      (streptavidin) targets to the probe (biotin) surface. The effect of probe space
      control on the efficiency of target capture is evaluated by examining the binding
      of streptavidin to thiolated biotin for a series of mixed monolayers. Surface
      modification is monitored by Fourier transform infrared reflection absorption
      spectroscopy (FTIR-RAS). The relative concentration of probe molecules at the
      surface is measured using X-ray photoelectron spectroscopy (XPS) measurements.
      Thiolated-biotin surfaces with optimized spacing show an increased capture
      efficiency for streptavidin relative to surfaces with nonoptimal or no control
      over probe spacing, as measured by surface plasmon resonance (SPR) spectroscopy.
      These results are of potential significance for the optimization and fabrication
      of micro- and nanoarrays used in chemical and biochemical measurements.

PMID- 19117478
TI  - Regioselective knitting of aniline via ortho-C-N bond fusion using OsO4 as a
      template.
AB  - This communication discloses the first examples of multiple ortho-C(arom)-N bond
      construction in aniline. The chemical reaction between aniline and OsO(4) has
      produced the higher homologues of aniline via ortho-C-N bond fusion. Formation of
      an open chain hexanilido ligand from the reaction clearly reveals the use of
      maximum possible coordination sites of the osmium template. The redox properties
      of the complexes are rich and have generated the possibilities of isolation of
      metal complexes containing organic radicals.

PMID- 19117479
TI  - Dispersive solid phase extraction for in-sorbent surface attenuated total
      reflection infrared detection.
AB  - The combination of dispersive solid phase extraction (DSPE) and attenuated total
      reflection (ATR) infrared spectroscopy is presented using the joint determination
      of sorbic and benzoic acids in juice samples as a model analytical problem. The
      dispersive extraction process allows the selective extraction of the target
      analytes from the sample matrix allowing their preconcentration prior to their
      infrared detection. The extraction efficiency is improved compared to the
      conventional procedures since the interaction between sorbent and analytes is
      favored with the stirring process. Moreover, the extracted analytes are directly
      determined in the sorbent. As no elution step is required, analyte dilutions and
      consumption of organic solvents are avoided. The proposed approach has been
      qualitative and quantitative studied. The hierarchical cluster analysis permits
      the sample classification according to the relative concentration of the
      analytes. The precision of the quantitative analysis was better than 6% with
      analyte recoveries in the range 87-90%. The proposed method was applied to the
      analysis of different commercial fruit juice samples. Finally, the main
      advantages and limitations of the new proposal are presented and compared with
      existing alternatives.

PMID- 19117480
TI  - Multiplex immunoassay using fluorescent-surface enhanced Raman spectroscopic dots
      for the detection of bronchioalveolar stem cells in murine lung.
AB  - Immunoassays using nanomaterials have been rapidly developed for the analysis of
      multiple biomolecules. Highly sensitive and biocompatible surface enhanced Raman
      spectroscopy-active nanomaterials have been used for biomolecule analysis by many
      research groups in order to overcome intrinsic problems of conventional
      immunoassays. We used fluorescent surface-enhanced Raman spectroscopic dots (F
      SERS dots) to detect biomolecules in this study. The F-SERS dots are composed of
      silver nanoparticle-embedded silica nanospheres, organic Raman tagging materials,
      and fluorescent dyes. The F-SERS dots demonstrated highly sensitive, selective,
      and multifunctional characteristics for multiplex targeting, tracking, and
      imaging of cellular and molecular events in the living organism. We successfully
      applied F-SERS dots for the detection of three cellular proteins, including CD34,
      Sca-1, and SP-C. These proteins are simultaneously expressed in bronchioalveolar
      stem cells (BASCs) in the murine lung. We analyzed the relative expression ratios
      of each protein in BASCs since external standards were used to evaluate SERS
      intensity in tissue. Quantitative comparisons of multiple protein expression in
      tissue were first attempted using SERS-encoded nanoprobes. Our results suggested
      that immunoassays using F-SERS dots offered significant increases in sensitivity
      and selectivity. Such immunoassays may serve as the primary next-generation
      labeling technologies for the simultaneous analysis of multiple biomolecules.

PMID- 19117482
TI  - Cleavage of a N-H bond of ammonia at room temperature by a germylene.
AB  - The reaction of LGeCl [1; L = CH{(CMe)(2,6-(i)Pr(2)C(6)H(3)N)}(2)] with 1,3-di
      tert-butylimidazol-2-ylidene results in the formation of the germylene L'Ge [2;
      L' = CH{(C=CH(2))(CMe)(2,6-(i)Pr(2)C(6)H(3)N)(2)}]. 2 reacts with ammonia under N
      H cleavage to give LGeNH(2) (3). This type of reaction can also be used to
      activate primary amines. 3 is characterized by microanalysis, multinuclear NMR
      spectroscopy, and X-ray structural analysis. The single-crystal X-ray structural
      analysis indicates 3 to be a monomer, and the germanium atom shows a trigonal
      pyramidal environment with a stereochemically active lone pair.

PMID- 19117481
TI  - Structural and functional glycosphingolipidomics by glycoblotting with an
      aminooxy-functionalized gold nanoparticle.
AB  - Glycosphingolipids (GSLs) synthesized in Golgi apparatus by sequential transfer
      of sugar residues to a ceramide lipid anchor are ubiquitously distributing on
      vertebrate plasma membranes. A standardized method allowing for high-throughput
      structural profiling and functional characterization of living cell surface GSLs
      is of growing importance because they function as crucial signal transduction
      molecules in various processes of dynamic cellular recognitions. However, methods
      are not available for amplification of GSLs, while the genomic scale PCR
      amplification permits large-scale mammalian proteomic analysis. Here we
      communicate such an approach to a novel "omics", namely, glycosphingolipidomics
      based on the "glycoblotting" method. The method, which involves selective
      ozonolysis of the C-C double bond in the ceramide moiety and subsequent
      enrichment of generated GSL aldehydes by chemical ligation using an aminooxy
      functionalized gold nanoparticle (aoGNP) should be of widespread utility for
      identifying and characterizing whole GSLs present in the living cell surfaces.
      The present protocol using glycoblotting permitted MALDI-TOFMS-based high
      throughput structural profiling of mouse brain gangliosides such as GM1,
      GD1a/GD1b, and GT1b for adult or GD3 in the case for the embryonic mouse. When
      mouse melanoma B16 cells were subjected to this protocol, it was demonstrated
      that gangliosides enriched from the plasma membranes are the only GM3 bearing
      microheteogeneity in the structure of the N-acyl chain. Surface plasmon resonance
      analysis revealed that aoGNP displaying whole GSLs blotted from mouse B16
      melanoma cell surfaces can be used directly for monitoring the specific
      interaction with the self-assembled monolayer (SAM) of Gg3Cer
      (gangliotriaosylceramide). Our results indicate that GSL-selective enrichment
      onto aoGNP from living cell surfaces allows for rapid reconstruction of plasma
      membrane models mimicking the intact GSL microdomain feasible for further
      structural and functional characterization.

PMID- 19117483
TI  - A new doubly interlocked [2]catenane.
AB  - The synthesis and the crystal structure of a doubly braided [2]catenane, a new
      molecular Solomon link, obtained by a 5-component-self-assembly process based on
      coordinative bonds, pi-donor/pi-acceptor interactions, and hydrogen bonding is
      reported.

PMID- 19117484
TI  - Alpha- to beta-(dmes)BiI(5) (dmes = dimethyl(2-ethylammonium)sulfonium dication):
      umbrella reversal of sulfonium in the solid state and short I...I interchain
      contacts--crystal structures, optical properties, and theoretical investigations
      of 1D iodobismuthates.
AB  - Syntheses, X-ray structural characterization, optical properties, and electronic
      structures of 1D metal(III) iodide hybrids, namely, alpha
      ((CH(3))(2)S(CH(2))(2)NH(3))BiI(5) (1a), beta-((CH(3))(2)S(CH(2))(2)NH(3))BiI(5)
      (1b), ((CH(3))(2)S(CH(2))(2)NH(3))SbI(5) (2), and
      (HO(2)C(C(6)H(4))CH(2)NH(3))BiI(4) (3), are reported. According to the results of
      single-crystal X-ray diffraction analyses, the 1D inorganic chains are
      constructed by corner-shared M(III)I(6) octahedra in 1a, 1b, and 2 and by edge
      shared ones in 3. In polymorphs 1a, 1b, and 2, the polymeric BiI(5)(2-) anionic
      chains are charge-balanced by the dimethyl(2-ethylammonium)sulfonium (dmes)
      dications. Complex 1a crystallizes in the polar space group of P2(1)cn. A
      spectacular umbrella reversal of half sulfonium parts together with the
      conformational change of half polymeric anions in the crystal structure of 1a
      occurs at moderate temperature (73 degrees C), leading to the beta-phase 1b,
      through a reversible single-crystal-to-single-crystal process. Complex 1b, as
      well as the isotype structure of 2, crystallize in the nonpolar acentric space
      group of P2(1)2(1)2(1). Because of their acentric structural characteristic,
      second harmonic generation (SHG) optical properties are observed in the
      polycrystalline powder samples of 1a, 1b, and 2. It is notable that the SHG
      signal of 1a is much stronger than that of 1b and 2 owing to the polarity of 1a.
      Remarkably, the peculiar dissymmetrical dication of dmes is able to modify the
      bonding features of the inorganic frameworks through shortening I...I distances
      between adjacent chains (d(I...I) < 4A). The structure of 3, which crystallizes
      in the triclinic space group P1, features a polymeric anionic chain constructed
      from edge-shared BiI(6) octahedra. The charge is balanced by the pairs of trans-4
      (ammoniummethyl)-cyclohexane-carboxylic acid, which are linked together via the H
      bonding between the carboxylic groups to form a pseudodication. The results of
      DFT calculations based on the structures of 1a and 3 indicate that the narrower
      band gap in 1 appears to be associated on the one hand with a sigma* I-p/Bi-s
      interaction that moves the Fermi level to higher energy and on the other hand
      with the interchain I...I contacts.

PMID- 19117485
TI  - LCMS and GCMS for the screening of alkaloids in natural and in vitro extracts of
      Leucojum aestivum.
AB  - HPLC coupled to a mass spectrometer (MS) was used for the analysis of
      galanthamine and lycorine in natural extracts of Leucojum aestivum and in their
      in vitro cultures grown with a precursor (ACC), inhibitors (AgNO(3), STS), or an
      absorber (KMnO(4)) of ethylene. The maximum galanthamine (0.002%) and lycorine
      (0.02%) concentrations in tissue cultures were obtained in the presence of
      KMnO(4). GCMS was used to investigate underivatized alkaloid mixtures from L.
      aestivum. Seven alkaloids were identified in in vivo bulbs. KMnO(4) led to the
      highest diversity of alkaloids in tissue culture extracts.

PMID- 19117486
TI  - Ambuic acid and torreyanic acid derivatives from the endolichenic fungus
      Pestalotiopsis sp.
AB  - Six new ambuic acid (1) derivatives (2-7) and a new torreyanic acid analogue (8)
      have been isolated from the crude extract of endophytic fungus Pestalotiopsis sp.
      inhabiting the lichen Multiclavula [corrected] sp. The structures of these
      compounds were elucidated primarily by NMR and MS methods, and their absolute
      configurations were assigned by application of the CD excitation chirality
      method. Compounds 1 and 2 displayed antimicrobial activity against the Gram
      positive bacterium Staphylococcus aureus.

PMID- 19117487
TI  - Skeletal and stereochemical diversification of tricyclic frameworks inspired by
      Ca(2+)-ATPase inhibitors, artemisinin and transtaganolide D.
AB  - Inspired by the common skeletal motifs of Ca(2+)-ATPases inhibitors involving
      artemisinin and transtaganolide D, small molecule collections with the three
      dimensional structural diversity of tricyclic systems were designed and
      expeditiously synthesized (4-5 steps). A synthetic strategy featuring
      stereochemical diversification of ring-junctions and control of cyclization modes
      was devised to access varied molecular architectures in a systematic fashion.

PMID- 19117488
TI  - A novel approach to the CDE ring system of pectenotoxin-4 triggered by
      VO(acac)(2)-induced epoxy-acetalization.
AB  - A novel approach to the CDE fragment of pectenotoxin-4 is described wherein the
      bicyclic acetal is constructed via a cascade cyclization induced by VO(acac)(2)
      epoxidation of a homoallylic alcohol.

PMID- 19117489
TI  - Synthesis of chromans via [3 + 3] cyclocoupling of phenols with allylic alcohols
      using a Mo/o-chloranil catalyst system.
AB  - The combination of a molybdenum complex (CpMoCl(CO)(3) or [CpMo(CO)(3)](2)) and o
      chloranil was used as a catalyst in the [3 + 3] cyclocoupling of phenols and
      allylic alcohols under microwave heating conditions. Substituted chromans were
      selectively obtained in moderate to good isolated yields.

PMID- 19117490
TI  - Designer discodermolide segments via ozonolysis of vinyl phosphonates.
AB  - To apply our collection of enantiopure 7-ring vinyl sulfones to probe the
      anticancer SAR of a series of computer-designed (+)-discodermolide analogs, the
      ozonolytic reactivity of transposed cyclic vinyl phosphonates was explored.
      Successful preparation of the desired aldehyde-esters and lactones from vinyl
      phosphonates via an oxidative cleavage-phosphite/methanol exchange sequence is
      described.

PMID- 19117491
TI  - Highly enantioselective vinyl additions of vinylaluminum to ketones catalyzed by
      a titanium(IV) catalyst of (S)-BINOL.
AB  - We report a novel asymmetric addition of vinyl group to ketones using
      vinylaluminum reagents catalyzed by in situ prepared Ti(O(i)Pr)(4) complexes of
      (S)-BINOL to afford diversified tertiary allylic alochols. Varieties of aromatic
      ketones bearing either an electron-donating or an electron-withdrawing
      substituent on the aromatic ring were examined to afford products in excellent
      enantioselectivities of up to 98% ee with high yields. A 10-fold scale-up
      reaction afforded the product in a similar yield with a comparable
      enantioselectivity. More importantly, additions of a variety of vinyl reagents
      including functionalized vinyls were demonstrated, affording tertiary allylic
      alcohols with good to excellent enantioselectivities of up to 96% ee.

PMID- 19117492
TI  - Synthesis and characterization of nonsteroidal-linked M(CO)(3)+ (M = 99mTc, Re)
      compounds based on the androgen receptor targeting molecule flutamide.
AB  - Androgen receptors are overexpressed in most primary and metastatic prostate
      cancers. A series of single photon emission computed tomography imaging agents
      (SPECT) utilizing the organometallic radioactive imaging species, fac
      99mTc(OH(2))(3)(CO)(3)+, were prepared on the basis of the structure of
      Flutamide, a potent nonsteroidal antiandrogen prostate cancer drug. Novel
      bifunctional chelate-linked Flutamide analogues were prepared using a newly
      developed universal alkylating reagent, 2-bromo-N-[4-nitro-3
      (trifluoromethyl)phenyl]-acetamide, 1. From compound 1, several ligands (i.e.,
      cysteine 2, histidine 5, imidazole 3) were conjugated to the flutamide derivative
      to yield targeting ligands capable of either tridentate or monodentate
      coordination in a "2 + 1" complex. fac-Re(CO)(3)+ complexes were prepared and
      characterized with the functionalized conjugates to yield fac-Re(CO)(3)(2-amino-3
      (1-(2-(4-nitro-3-(trifluoromethyl)phenylamino)-2-oxoethyl)-1H-imidazol-4-yl)
      propanoate), 4, fac-Re (CO)(3)(2-(S-cysteinyl)-N-[4-nitro-3-(trifluoromethyl)
      phenyl]-acetamide), 6, and fac-Re(CO)(3)(picolinate)(2-(1H-imidazol-1-yl)-N-[4
      nitro-3-(trifluoromethyl)phenyl]-acetamide), 7. The corresponding radioactive
      99mTc analogues were prepared and stability studies of the radioactive compounds
      were also conducted.

PMID- 19117493
TI  - Adhesion-induced unclasping of cytoplasmic tails of integrin alpha(IIb)beta3.
AB  - Integrin alpha(IIb)beta(3) plays a pivotal role in hemostasis and thrombosis by
      mediating adhesive interactions of platelets. Binding of alpha(IIb)beta(3) to its
      physiological ligands, immobilized fibrinogen and fibrin, induces outside-in
      signaling in platelets, leading to their adhesion and spreading even without
      prior stimulation by agonists. Implicit in these phenomena is a requirement for
      the linkage between integrins' cytoplasmic tails and intracellular proteins.
      However, the nature of the initiating signal has not been established. In this
      study, we examined whether binding of alpha(IIb)beta(3) to immobilized
      fibrin(ogen), per se, triggers interaction of the integrin with cytoplasmic
      proteins. Using the integrin-binding skelemin fragment as a marker of exposure of
      residues involved in the clasp between alpha(IIb) and beta(3) cytoplasmic tails,
      we showed that its binding site in the membrane-proximal beta(3) 715-730 segment
      is cryptic and becomes exposed as a result of binding of isolated
      alpha(IIb)beta(3) to immobilized ligands. Furthermore, the skelemin-like protein
      present in platelets and CHO cells does not associate with alpha(IIb)beta(3) in
      resting platelets or suspended alpha(IIb)beta(3)-expressing CHO cells but is
      recruited to integrin during cell adhesion. In addition, not only beta(3) but
      also the membrane-proximal 989-1000 segment of the alpha(IIb) cytoplasmic tail
      binds the skelemin fragment. Finally, the same residues, alpha(IIb) Val(990),
      alpha(IIb) Arg(995), and beta(3) His(722), involved in the formation of the clasp
      between the tails are also required for skelemin binding. These studies suggest
      that ligation of alpha(IIb)beta(3) by immobilized ligands during platelet
      adhesion induces a transmembrane conformation change in the integrin, resulting
      in unclasping of the complex between the membrane-proximal parts of cytoplasmic
      tails, thereby unmasking residues involved in binding the skelemin-like protein.
      Thus, the junction between alpha(IIb) and beta(3) cytoplasmic tails may contain
      the critical structural information for the initiation of outside-in signaling.

PMID- 19117494
TI  - Radio-frequency-free cell for electron capture dissociation in tandem mass
      spectrometry.
AB  - A radio frequency-free (RFF), analyzer-independent cell has been devised for
      electron-capture dissociation (ECD) of ions. The device is based on interleaving
      a series of electrostatic lenses with the periodic structure of magnetostatic
      lenses commonly found in a traveling wave tube. The RFF
      electrostatic/magnetostatic ECD cell was installed in a Finnigan TSQ700 ESI
      triple quadrupole (QqQ) spectrometer, and its performance was evaluated by
      recording product-ion spectra of doubly protonated substance P, doubly protonated
      gramicidin S, doubly protonated neurotensin, and triply protonated neurotensin.
      These spectra were readily obtained without recourse to a buffering gas or
      synchronizing electron injection with a specific phase of an RF field. The mass
      spectra produced with the modified instrument appear in all respects (other than
      resolution and mass accuracy, which were limited by the mass spectrometer used)
      to be at least as good for purposes of peptide identification as those recorded
      with Fourier transform ion cyclotron resonance (FT ICR) instruments; however, the
      effort and time to produce the mass spectra were much less than required to
      produce their FT ICR counterparts. The cell's design and compact construction
      should allow it to be incorporated at relatively little cost into virtually any
      type of tandem mass spectrometer, for example, triple quadrupole, hybrid
      quadrupole ion trap, hybrid quadrupole time-of-flight, or even FT-ICR.

PMID- 19117495
TI  - Computationally and experimentally derived general rules for fragmentation of
      various glycosyl bonds in sodium adduct oligosaccharides.
AB  - Mechanisms of fragmentation of glycosyl bond linkages in various saccharides were
      investigated by using computational calculations to find general rules of
      fragmentation of sodiated oligosaccharides in mass spectrometry. The calculations
      revealed that alpha-Glc, alpha-Gal, beta-Man, alpha-Fuc, beta-GlcNAc, and beta
      GalNAc linkages were cleaved more easily than beta-Glc, beta-Gal, and alpha-Man
      linkages because the transition states of the former were stabilized by the
      anomeric effect. The 1-6 linkage was more stable than the others, since
      saccharides with flexible 1-6 linkages were more stabilized in energy than the
      other linkages by the sodium cation. The sialyl linkage was the most labile of
      all the linkages investigated. Comparison of activation energies and binding
      affinities to the sodium cation revealed an increase in activation energy in
      proportion to the increment in binding affinity. The calculated stabilities of
      glycosyl bonds were: alpha-Man (Manalpha1-3Man, Manalpha1-4Man, Manalpha1-6Man) >
      beta-Gal (Galbeta1-4Gal) > alpha-GalNAc (GalNAcalpha1-4GalNAc) > beta-Man
      (Manbeta1-4GlcNAc) > alpha-Gal (Galalpha1-3Gal, Galalpha1-4Gal, Galalpha1-6Gal) >
      beta-Man (Manbeta1-4Man) > beta-GalNAc (GalNAcbeta1-4GalNAc) > alpha-Fuc
      (Fucalpha1-6GlcNAc) > alpha-Fuc (Fucalpha1-4GlcNAc) > beta-GlcNAc (GlcNAcbeta1
      4GlcNAc) > alpha-Fuc (Fucalpha1-3GlcNAc) > alpha-NeuNAc (NeuNAcalpha2-3Gal,
      NeuNAcalpha2-6Gal); this result was close to the experimentally deduced trend.
      These theoretically and experimentally derived general rules for fragmentation
      should be useful for analyzing the experimentally obtained mass spectra of
      oligosaccharides.

PMID- 19117496
TI  - Outcomes from a Respiratory Coordinated Care Program (RCCP) providing community
      based interventions for COPD patients from 1998 to 2006.
AB  - The Respiratory Coordinated Care Program (RCCP) based at St George Hospital, is a
      specialised community program designed to assist people with advanced COPD (DRG
      groupings E65A/E65B) to live optimally well at home. The aim of the program is to
      reduce hospital admission rates, readmission rates, and hospital length of stay
      (LOS). Additional components of RCCP include a Pulmonary Rehabilitation program
      and an early discharge service. An improvement in patient outcomes over
      subsequent years 1998-2006, is demonstrated when compared to the national peer
      DRG with regards to LOS, readmission rates and hospital admissions per patient
      per year, pre and post recruitment to the RCCP. The chronic long term component
      of the RCCP shows that the mean LOS and the number of hospital admissions was
      significantly lower when compared to the national DRG average. Since its
      inception, the RCCP has consistently demonstrated a cost effective reduction in
      hospital admission rates, LOS and reduced readmission.

PMID- 19117497
TI  - A woman centred service in termination of pregnancy: a grounded theory study.
AB  - The issue of abortion is contentious. It challenges those involved emotionally
      and ethically and, although in the UK it is set within legal parameters, it
      remains controversial. The involvement of nurses and midwives in abortion care
      has not been explored to any great depth. In the UK, there has been a sustained
      increase in the number of medical compared to surgical terminations over the last
      decade. Nurses/midwives are at the forefront of this procedure and, because of
      the current political climate, their involvement is likely to increase in the
      future. This grounded theory study aimed to explore how nurses and midwives
      perceive their role with women undergoing termination of pregnancy and how they
      cope with their increased involvement with these women.

PMID- 19117498
TI  - Relationships between aggression management training, perceived self-efficacy and
      rural general hospital nurses' experiences of patient aggression.
AB  - Relationships between nurses' experiences of patient aggression in the previous
      three months, participation in aggression management training in the previous
      five years and perceived self-efficacy in dealing with patient aggression are
      reported. Over 76 per cent of general hospital nurses employed by a rural Area
      Health Service in New South Wales, Australia experienced patient aggression
      within a three-month period. Registered Nurses and Midwifes were most affected,
      with over 83 per cent experiencing recent patient aggression. Most of this
      aggression was in the form of verbal abuse. Almost 40 per cent of nurses had not
      participated in aggression management training or updates in the previous five
      years. Approximately 70 per cent of survey respondents reported their perceived
      self-efficacy in dealing with patient aggression in the low to medium-high range.
      No significant association was detected between participation in aggression
      management training in the previous five years and the frequency of patient
      aggression experienced in the previous three months. Significant though very weak
      associations were detected between participation in aggression management
      training, the proportion of patient aggression experienced as verbal abuse and
      perceived self-efficacy in dealing with patient aggression. The findings of this
      and other studies highlight the need for more rigorous approaches to evaluating
      the effectiveness of aggression management training and undertaking patient
      aggression management research more broadly.

PMID- 19117499
TI  - Senior nurses as patients: narratives of special and meagre care.
AB  - Like the general population, nurses become patients within the health care
      services available to them. They write anecdotal accounts of their experience and
      research the experience of their colleagues. This paper reports a small
      descriptive study of how the positions of senior nurses who experienced a life
      threatening condition influenced their illness trajectories. Eleven nurses in
      both New Zealand and Australia told stories of their experiences which focussed
      on intercessions/intervention by themselves, their family and the health care
      team. Themes identified were: looking after our own, the gaze of family and
      friends in advocacy and intercession, stereotypes of nurses as patients, senior
      nurses as vulnerable patients - existential healing through the small things, and
      senior nurses as knowledgeable people. Within these themes were narratives of
      special and meagre care. The authors conclude that all senior nurses should
      receive care that is regardful of who they are as senior nurses and vulnerable
      patients.

PMID- 19117500
TI  - Prevalence, risk factors and strategies to prevent dehydration in older adults.
AB  - The treatment of dehydration in older adults admitted from residential care to an
      acute hospital setting may lead to haemodynamic stability. There is however an
      increased risk for short or long term alterations in physiological, cognitive and
      psychological status and ultimately, decreased quality of life. Such acute care
      admissions could be decreased where preventative strategies tailored to address
      individual risk factors are combined with more frequent assessment of the degree
      of hydration. The questionable reliability of assessment criteria in older adults
      increases the need to use multiple signs and symptoms in the identification and
      differentiation of early and late stages of dehydration. This article reviews
      various risk factors, explores the reliability of clinical signs and symptoms and
      reinforces the need to use multiple patient assessment cues if nurses are to
      differentiate between, and accurately respond to, the various causes of
      dehydration. Specific strategies to maintain hydration in older adults are also
      identified.

PMID- 19117501
TI  - Supporting fathers in the transition to parenthood.
AB  - Knowledge of the experience of parenthood is usually from a woman's perspective.
      The resulting outcome is that knowledge about the experience of fatherhood has
      been limited. Fathers are starting to change this situation by sharing their
      experience as is evidenced by the overall response of 267 fathers to this study.
      This paper focuses on the exploration of 22 men's feelings and beliefs about
      fatherhood; and their expectations and views about parenting. The paper will also
      investigate how fathers' antenatal expectations matched the reality of early
      family life including emotional well-being, attitudes to parenting, adjustment to
      family life and sources of support. The quantitative and qualitative data of the
      22 fathers who responded to both the antenatal and postnatal questionnaires used
      within this paper are drawn from a larger Queensland survey of women and men
      during the antenatal and postnatal period.

PMID- 19117502
TI  - A demographic snapshot of midwives in Victoria.
AB  - Midwifery in Victoria has experienced significant change over the last twenty
      years. Over more recent years, midwifery workforce issues have become prominent
      with studies highlighting an ageing midwifery population and a high proportion of
      part time employment. During a study conducted in 2005 that explored midwives'
      attitudes to online and computer based learning the demographic data proved to
      warrant more detailed analysis. This paper presents a discussion on that data.
      Participants for the study were drawn from the membership of the Australian
      College of Midwives (ACM) Victorian branch. However, while the sample was small
      (n=169), the findings presented in the paper add to the existing body of
      knowledge around the midwifery workforce in Victoria. They reinforce that the
      midwifery workforce remained an ageing one, predominantly female, and a
      significant percentage were employed on part time or casual bases. With graduates
      emerging from recently introduced undergraduate midwifery programs, it is argued
      that it is timely for larger studies of the midwifery workforce to be conducted.
      Studies should seek to explore a range of factors such as reasons why midwives
      are choosing not to work in full time employment.

PMID- 19117503
TI  - A prospective descriptive study of women attending a colposcopy clinic.
AB  - This paper reports the findings of a prospective convenience sample cohort study
      investigating self-reported purpose of pap smears and worry interference
      associated with having abnormal pap smear results in women attending a public
      colposcopy service between 05 April and 19 December 2003. Intrusive thoughts
      about cancer have been postulated to be associated with dysfunction in women at
      increased risk of developing breast or ovarian cancer. A study designed
      questionnaire and the Multidimensional Health Locus of Control was completed by
      the women whilst waiting to have colposcopy. This study shows that Asian women
      need to have information about abnormal pap smear results explained well in order
      to avoid intrusive thoughts and anxiety. It also demonstrates that nurses provide
      a key role in providing information that leads to less concern and better
      understanding of the concepts.

PMID- 19117504
TI  - Perception of intensive care unit stressors in Malaysian Federal Territory
      hospitals.
AB  - The Intensive Care Unit (ICU) is a therapeutic place for monitoring critically
      ill patients. However, it is a stressful area for the patients and it is causing
      them great anxiety. Previous studies have identified three groups of stressors in
      ICU namely; physical, psychological and environmental. The aims of this study
      were to determine the ICU stressors as experienced by patients and to determine
      the level of stressors felt by patients in ICU. A cross sectional study was done
      on 70 patients from two tertiary hospitals in Malaysia. A face-to-face interview
      with structured questionnaire was used for patients. Data collection occurred
      from 15 December 2006 to 31 January 2007. The five major ICU stressors perceived
      by patients were pain, being stuck with needles, boredom, missing their spouses
      and being too hot/cold. The ICU physical stressors were the major items ranked by
      post ICU patients. The findings from this study provided a set of baseline
      information to the health care providers, particularly ICU nurses in Malaysia,
      with which to provide better care for the patients in ICU.

PMID- 19117506
TI  - A checklist of macroparasites of Liza haematocheila (Temminck & Schlegel)
      (Teleostei: Mugilidae).
AB  - BACKGROUND: The mugilid fish Liza haematocheila (syn. Mugil soiuy), native to
      the Western North Pacific, provides opportunities to examine the changes of its
      parasite fauna after its translocation to the Sea of Azov and subsequent
      establishment in the Black Sea. However, the information on macroparasites of
      this host in both ranges of its current distribution comes from isolated studies
      published in difficult-to-access literature sources. MATERIALS AND METHODS: Data
      from 53 publications, predominantly in Chinese, Russian and Ukrainian, were
      compiled from an extensive search of the literature and the Host-Parasite
      Database maintained up to 2005 at the Natural History Museum, London. RESULTS:
      The complete checklist of the metazoan parasites of L. haematocheila throughout
      its distributional range comprises summarised information for 69 nominal species
      of helminth and ectoparasitic crustacean parasites, from 45 genera and 27
      families (370 host-parasite records in total) and includes the name of the
      parasite species, the area/locality of the host capture, and the author and date
      of the published record. The taxonomy is updated and the validity of the records
      and synonymies are critically evaluated. A comparison of the parasite faunas
      based on the records in the native and introduced/invasive range of L.
      haematocheila suggests that a large number of parasite species was 'lost' in the
      new distributional range whereas an even greater number was 'gained'. CONCLUSION:
      Although the present checklist provides information that will facilitate future
      studies, the interesting question of macroparasite faunal diversity in L.
      haematocheila in its natural and introduced/invasive ranges cannot be dealt with
      the current data because of unreliability associated with the large number of non
      documented and questionable records. This stresses the importance of data quality
      analysis in using host-parasite database and checklist data.

PMID- 19117505
TI  - Gene methylation profiles of normal mucosa, and benign and malignant colorectal
      tumors identify early onset markers.
AB  - BACKGROUND: Multiple epigenetic and genetic changes have been reported in
      colorectal tumors, but few of these have clinical impact. This study aims to
      pinpoint epigenetic markers that can discriminate between non-malignant and
      malignant tissue from the large bowel, i.e. markers with diagnostic potential.
      The methylation status of eleven genes (ADAMTS1, CDKN2A, CRABP1, HOXA9, MAL,
      MGMT, MLH1, NR3C1, PTEN, RUNX3, and SCGB3A1) was determined in 154 tissue samples
      including normal mucosa, adenomas, and carcinomas of the colorectum. The gene
      specific and widespread methylation status among the carcinomas was related to
      patient gender and age, and microsatellite instability status. Possible CIMP
      tumors were identified by comparing the methylation profile with microsatellite
      instability (MSI), BRAF-, KRAS-, and TP53 mutation status. RESULTS: The mean
      number of methylated genes per sample was 0.4 in normal colon mucosa from tumor
      free individuals, 1.2 in mucosa from cancerous bowels, 2.2 in adenomas, and 3.9
      in carcinomas. Widespread methylation was found in both adenomas and carcinomas.
      The promoters of ADAMTS1, MAL, and MGMT were frequently methylated in benign
      samples as well as in malignant tumors, independent of microsatellite
      instability. In contrast, normal mucosa samples taken from bowels without tumor
      were rarely methylated for the same genes. Hypermethylated CRABP1, MLH1, NR3C1,
      RUNX3, and SCGB3A1 were shown to be identifiers of carcinomas with microsatellite
      instability. In agreement with the CIMP concept, MSI and mutated BRAF were
      associated with samples harboring hypermethylation of several target genes.
      CONCLUSION: Methylated ADAMTS1, MGMT, and MAL are suitable as markers for early
      tumor detection.

PMID- 19117507
TI  - Diagnosis of foot-and mouth disease by real time reverse transcription polymerase
      chain reaction under field conditions in Brazil.
AB  - BACKGROUND: Foot-and-mouth disease (FMD) is an economically important and highly
      contagious viral disease that affects cloven-hoofed domestic and wild animals.
      Virus isolation and enzyme-linked immunosorbent assay (ELISA) are the gold
      standard tests for diagnosis of FMD. As these methods are time consuming, assays
      based on viral nucleic acid amplification have been developed. RESULTS: A
      previously described real-time reverse transcriptase polymerase chain reaction
      (RT-PCR) assay with high sensitivity and specificity under laboratorial and
      experimental conditions was used in the current study. To verify the
      applicability of this assay under field conditions in Brazil, 460 oral swabs from
      cattle were collected in areas free of FMD (n = 200) and from areas with
      outbreaks of FMD (n = 260). Three samples from areas with outbreaks of FMD were
      positive by real-time RT-PCR, and 2 of those samples were positive by virus
      isolation and ELISA. Four other samples were considered inconclusive by real-time
      RT-PCR (threshold cycle [Ct] > 40); whereas all 200 samples from an area free of
      FMD were real-time RT-PCR negative. CONCLUSION: real-time RT-PCR is a powerful
      technique for reliable detection of FMDV in a fraction of the time required for
      virus isolation and ELISA. However, it is noteworthy that lack of infrastructure
      in certain areas with high risk of FMD may be a limiting factor for using real
      time RT-PCR as a routine diagnostic tool.

PMID- 19117508
TI  - Neonatal high pressure hydrocephalus is associated with elevation of pro
      inflammatory cytokines IL-18 and IFNgamma in cerebrospinal fluid.
AB  - BACKGROUND: In human neonatal high pressure hydrocephalus (HPHC), diffuse white
      matter injury and gliosis predispose to poor neuro-developmental outcome. The
      underlying mechanism for diffuse white matter damage in neonatal HPHC is still
      unclear. Analogous to inflammatory white matter damage after neonatal
      hypoxemia/ischemia, we hypothesized that pro-inflammatory cytokines could be
      involved in neonatal HPHC. If so, early anti-inflammatory therapy could
      ameliorate white matter damage in HPHC, before irreversible apoptosis has
      occurred. In HPHC and control neonates, we therefore aimed to compare
      cerebrospinal fluid (CSF) concentrations of IL18, IFNgamma and sFasL (interleukin
      18, interferon gamma and apoptosis marker soluble-Fas ligand, respectively).
      METHODS: In neonatal HPHC (n = 30) and controls (n = 15), we compared CSF
      concentrations of IL18, IFNgamma and sFasL using sandwich ELISA. HPHC was grouped
      according to etiology: spina bifida aperta (n = 20), aqueduct stenosis (n = 4),
      and fetal intra-cerebral haemorrhage (n = 6). Neonatal control CSF was derived
      from otherwise healthy neonates (n = 15), who underwent lumbar puncture for
      exclusion of meningitis. RESULTS: In all three HPHC groups, CSF IL18
      concentrations were significantly higher than control values, and the fetal
      intracranial haemorrhage group was significantly higher than SBA group.
      Similarly, in all HPHC groups CSF-IFNgamma concentrations significantly exceeded
      the control group. In both HPHC and control neonates, CSF FasL concentrations
      remained within the range of reference values. CONCLUSION: Independent of the
      pathogenesis, neonatal HPHC is associated with the activation of the pro
      inflammatory cytokines (IL-18 and IFNgamma) in the CSF, whereas CSF apoptosis
      biomarkers (sFasL) were unchanged. This suggests that anti-inflammatory treatment
      (in addition to shunting) could be helpful to preserve cerebral white matter.

PMID- 19117509
TI  - Arduous implementation: does the Normalisation Process Model explain why it's so
      difficult to embed decision support technologies for patients in routine clinical
      practice.
AB  - BACKGROUND: Decision support technologies (DSTs, also known as decision aids)
      help patients and professionals take part in collaborative decision-making
      processes. Trials have shown favorable impacts on patient knowledge,
      satisfaction, decisional conflict and confidence. However, they have not become
      routinely embedded in health care settings. Few studies have approached this
      issue using a theoretical framework. We explained problems of implementing DSTs
      using the Normalization Process Model, a conceptual model that focuses attention
      on how complex interventions become routinely embedded in practice. METHODS: The
      Normalization Process Model was used as the basis of conceptual analysis of the
      outcomes of previous primary research and reviews. Using a virtual working
      environment we applied the model and its main concepts to examine: the
      'workability' of DSTs in professional-patient interactions; how DSTs affect
      knowledge relations between their users; how DSTs impact on users' skills and
      performance; and the impact of DSTs on the allocation of organizational
      resources. RESULTS: A conceptual analysis using the Normalization Process Model
      provided insight on implementation problems for DSTs in routine settings. Current
      research focuses mainly on the interactional workability of these technologies,
      but factors related to divisions of labor and health care, and the organizational
      contexts in which DSTs are used, are poorly described and understood. CONCLUSION:
      The model successfully provided a framework for helping to identify factors that
      promote and inhibit the implementation of DSTs in healthcare and gave us insights
      into factors influencing the introduction of new technologies into contexts where
      negotiations are characterized by asymmetries of power and knowledge. Future
      research and development on the deployment of DSTs needs to take a more holistic
      approach and give emphasis to the structural conditions and social norms in which
      these technologies are enacted.

PMID- 19117510
TI  - Smoking characteristics of Polish immigrants in Dublin.
AB  - BACKGROUND: This study examined two main hypotheses: a) Polish immigrants'
      smoking estimates are greater than their Irish counterparts (b) Polish immigrants
      purchasing cigarettes from Poland smoke "heavier" (>/= 20 cigarettes a day) when
      compared to those purchasing cigarettes from Ireland. The study also set out to
      identify significant predictors of 'current' smoking (some days and everyday)
      among the Polish immigrants. METHODS: Dublin residents of Polish origin (n =
      1,545) completed a previously validated Polish questionnaire in response to an
      advertisement in a local Polish lifestyle magazine over 5 weekends (July-August,
      2007). The Office of Tobacco Control telephone-based monthly survey data were
      analyzed for the Irish population in Dublin for the same period (n = 484).
      RESULTS: Age-sex adjusted smoking estimates were: 47.6% (95% Confidence Interval
      [CI]: 47.3%; 48.0%) among the Poles and 27.8% (95% CI: 27.2%; 28.4%) among the
      general Irish population (p < 0.001). Of the 57% of smokers (n = 345/606) who
      purchased cigarettes solely from Poland and the 33% (n = 198/606) who purchased
      only from Ireland, 42.6% (n = 147/345) and 41.4% (n = 82/198) were "heavy"
      smokers, respectively (p = 0.79). Employment (Odds Ratio [OR]: 2.89; 95% CI: 1.25
      6.69), lower education (OR: 3.76; 95%CI: 2.46-5.74), and a longer stay in Ireland
      (>24 months) were significant predictors of current smoking among the Poles. An
      objective validation of the self-reported smoking history of a randomly selected
      sub-sample immigrant group, using expired carbon monoxide (CO) measurements,
      showed a highly significant correlation coefficient (r = 0.64) of expired CO
      levels with the reported number of cigarettes consumed (p < 0.0001). CONCLUSION:
      Polish immigrants' smoking estimates are higher than their Irish counterparts,
      and particularly if employed, with only primary-level education, and are overseas
      >2 years.

PMID- 19117511
TI  - Current status of haploidentical stem cell transplantation for leukemia.
AB  - Haploidentical hematopoietic stem cell transplantation has made tremendous
      progress over the past 20 years and has become a feasible option for leukemia
      patients without a HLA identical sibling donor. The early complications of severe
      graft-versus-host disease (GVHD), graft failure and delayed engraftment, as well
      as disease recurrence have limited the use of this approach. Newer strategies
      have been applied and overcome some of the problems, including the use of T-cell
      depleted graft, "mega" dose of stem cells, intensive post-transplant
      immunosuppression and manipulation of the graft. These have decreased the
      transplant related mortality and GVHD associated with haploidentical
      transplantation, however, the major problems of disease relapse and infection,
      which related to late immune reconstitution, limit the development of
      haploidentical HSCT. Future challenges remain in improving post-transplant immune
      reconstitution and finding the best approach to reduce the incidence and severity
      of GVHD, while preserving graft-versus-leukemia effect to prevent the recurrence
      of underlying malignancy.

PMID- 19117512
TI  - Laparoscopic-assisted small bowel resection for treatment of adult small bowel
      intussusception: a case report.
AB  - BACKGROUND: Intussuception is a rare cause of intestinal obstruction in adults.
      Diagnosis is often difficult due to the variable and sometimes episodic nature of
      symptoms. Surgery is the recommended treatment option in adults if the diagnosis
      is proven. CASE PRESENTATION: We present a case of a 33 year old Caucasian female
      admitted with a small bowel obstruction and no history of previous abdominal
      surgery. Patient did not improve with medical management consisting of bowel rest
      and nasogastric tube decompression. Surgery was consulted and patient was taken
      to the operating room for a laparoscopic-assisted small bowel resection for a
      small bowel intussusception caused by a submucosal fibroma. CONCLUSION: Our case
      highlights the feasibility and potential benefits of laparoscopy in assisting the
      diagnosis and treatment of small bowel obstructions.

PMID- 19117513
TI  - Implementing an innovative consent form: the PREDICT experience.
AB  - BACKGROUND: In the setting of coronary angiography, generic consent forms permit
      highly variable communication between patients and physicians. Even with the
      existence of multiple risk models, clinicians have been unable to readily access
      them and thus provide patients with vague estimations regarding risks of the
      procedure. METHODS: We created a web-based vehicle, PREDICT, for embedding
      patient-specific estimates of risk from validated multivariable models into
      individualized consent documents at the point-of-care. Beginning August 2006,
      outpatients undergoing coronary angiography at the Mid America Heart Institute
      received individualized consent documents generated by PREDICT. In February 2007
      this approach was expanded to all patients undergoing coronary angiography within
      the four Kansas City hospitals of the Saint Luke's Health System. Qualitative
      research methods were used to identify the implementation challenges and
      successes with incorporating PREDICT-enhanced consent documents into routine
      clinical care from multiple perspectives: administration, information systems,
      nurses, physicians, and patients. RESULTS: Most clinicians found usefulness in
      the tool (providing clarity and educational value for patients) and satisfaction
      with the altered processes of care, although a few cardiologists cited delayed
      patient flow and excessive patient questions. The responses from administration
      and patients were uniformly positive. The key barrier was related to informatics.
      CONCLUSION: This preliminary experience suggests that successful change in
      clinical processes and organizational culture can be accomplished through
      multidisciplinary collaboration. A randomized trial of PREDICT consent,
      leveraging the accumulated knowledge from this first experience, is needed to
      further evaluate its impact on medical decision-making, patient compliance, and
      clinical outcomes.

PMID- 19117514
TI  - Malignant melanoma associated with a blue naevus: a case report.
AB  - INTRODUCTION: Combined malignant naevi are characterised pathologically by the
      association of a melanoma with one or more different types of benign melanocytic
      naevi in a single lesion. CASE PRESENTATION: We show here a case of malignant
      combined naevus made up of a blue naevus and a melanoma, presenting as a slowly
      progressing and asymptomatic pigmented lesion on the trunk of a 35-year-old man.
      Dermoscopic examination was not conclusive for a malignant lesion, showing only
      an atypical brown pigment network. The definitive diagnosis was reached only at
      the hystopathological examination. CONCLUSION: This finding suggests that
      combined naevi should be always excised and histologically examined to achieve a
      correct diagnosis and avoid risk of misclassification.

PMID- 19117515
TI  - Molecular profiling of T-helper immune genes during dengue virus infection.
AB  - In this study, we provide a comprehensive molecular profiling of the involvement
      of T- helper (Th) genes during dengue virus infection of different cell types.
      The Th gene profiles of three human cell types (monocytes, T-cells and
      hepatocytes) were analyzed simultaneously via array-based RT-PCR upon infection
      with dengue virus. Differential regulation of 41 Th genes was identified and of
      which 20 of those genes may contribute to immuno-pathogenesis of dengue virus
      infection by regulating inflammation, thrombocytopenia and vascular permeability.
      Among the strongly up-regulated genes were the RANTES, CC-CKR3, IRF4, CLEC2C, IL
      6 and TLR6, which are potent inducer of inflammation and vascular permeability.
      Profiling genes obtained from this study may serve as potential biomarkers and
      the modulation of Th immune responses during dengue virus infection has important
      implications in disease outcome.

PMID- 19117516
TI  - Mismatch oligonucleotides in human and yeast: guidelines for probe design on
      tiling microarrays.
AB  - BACKGROUND: Mismatched oligonucleotides are widely used on microarrays to
      differentiate specific from nonspecific hybridization. While many experiments
      rely on such oligos, the hybridization behavior of various degrees of mismatch
      (MM) structure has not been extensively studied. Here, we present the results of
      two large-scale microarray experiments on S. cerevisiae and H. sapiens genomic
      DNA, to explore MM oligonucleotide behavior with real sample mixtures under
      tiling-array conditions. RESULTS: We examined all possible nucleotide
      substitutions at the central position of 36-nucleotide probes, and found that
      nonspecific binding by MM oligos depends upon the individual nucleotide
      substitutions they incorporate: C-->A, C-->G and T-->A (yielding purine-purine
      mispairs) are most disruptive, whereas A-->X were least disruptive. We also
      quantify a marked GC skew effect: substitutions raising probe GC content exhibit
      higher intensity (and vice versa). This skew is small in highly-expressed regions
      (+/- 0.5% of total intensity range) and large (+/- 2% or more) elsewhere.
      Multiple mismatches per oligo are largely additive in effect: each MM added in a
      distributed fashion causes an additional 21% intensity drop relative to PM, three
      fold more disruptive than adding adjacent mispairs (7% drop per MM). CONCLUSION:
      We investigate several parameters for oligonucleotide design, including the
      effects of each central nucleotide substitution on array signal intensity and of
      multiple MM per oligo. To avoid GC skew, individual substitutions should not
      alter probe GC content. RNA sample mixture complexity may increase the amount of
      nonspecific hybridization, magnify GC skew and boost the intensity of MM oligos
      at all levels.

PMID- 19117517
TI  - Impact of contractile reserve on acute response to cardiac resynchronization
      therapy.
AB  - BACKGROUND: Cardiac resynchronization therapy (CRT) provides benefit for
      congestive heart failure, but still 30% of patients failed to respond to such
      therapy. This lack of response may be due to the presence of significant amount
      of scar or fibrotic tissue at myocardial level. This study sought to investigate
      the potential impact of myocardial contractile reserve as assessed during
      exercise echocardiography on acute response following CRT implantation. METHODS:
      Fifty-one consecutive patients with heart failure (LV ejection fraction 27% +/-
      5%, 67% ischemic cardiomyopathy) underwent exercise Doppler echocardiography
      before CRT implantation to assess global contractile reserve (improvement in LV
      ejection fraction) and local contractile reserve in the region of the LV pacing
      lead (assessed by radial strain using speckle tracking analysis). Responders were
      defined by an increase in stroke volume > or = 15% after CRT. RESULTS: Compared
      with nonresponders, responders (25 patients) showed a greater exercise-induced
      increase in LV ejection fraction, a higher degree of mitral regurgitation and a
      significant extent of LV dyssynchrony. The presence of contractile reserve was
      directly related to the acute increase in stroke volume (r = 0.48, p < 0.001).
      Baseline myocardial deformation as well as contractile reserve in the LV pacing
      lead region was greater in responders during exercise than in nonresponders (p <
      0.0001). CONCLUSION: The present study showed that response to CRT largely
      depends not only on the extent of LV dyssynchrony and the severity of mitral
      regurgitation but also on the presence of contractile reserve.

PMID- 19117518
TI  - OpenADAM: an open source genome-wide association data management system for
      Affymetrix SNP arrays.
AB  - BACKGROUND: Large scale genome-wide association studies have become popular since
      the introduction of high throughput genotyping platforms. Efficient management of
      the vast array of data generated poses many challenges. DESCRIPTION: We have
      developed an open source web-based data management system for the large amount of
      genotype data generated from the Affymetrix GeneChip Mapping Array and Affymetrix
      Genome-Wide Human SNP Array platforms. The database supports genotype calling
      using DM, BRLMM, BRLMM-P or Birdseed algorithms provided by the Affymetrix Power
      Tools. The genotype and corresponding pedigree data are stored in a relational
      database for efficient downstream data manipulation and analysis, such as
      calculation of allele and genotype frequencies, sample identity checking, and
      export of genotype data in various file formats for analysis using commonly
      available software. A novel method for genotyping error estimation is implemented
      using linkage disequilibrium information from the HapMap project. All
      functionalities are accessible via a web-based user interface. CONCLUSION:
      OpenADAM provides an open source database system for management of Affymetrix
      genome-wide association SNP data.

PMID- 19117519
TI  - A rapid biosensor-based method for quantification of free and glucose-conjugated
      salicylic acid.
AB  - BACKGROUND: Salicylic acid (SA) is an important signalling molecule in plant
      defenses against biotrophic pathogens. It is also involved in several other
      processes such as heat production, flowering, and germination. SA exists in the
      plant as free SA and as an inert glucose conjugate (salicylic acid 2-O-beta-D
      glucoside or SAG). Recently, Huang et al. developed a bacterial biosensor that
      responds to free SA but not SAG, designated as Acinetobacter sp. ADPWH_lux. In
      this paper we describe an improved methodology for Acinetobacter sp. ADPWH_lux
      based free SA quantification, enabling high-throughput analysis, and present an
      approach for the quantification of SAG from crude plant extracts. RESULTS: On the
      basis of the original biosensor-based method, we optimized extraction and
      quantification. SAG content was determined by treating crude extracts with beta
      glucosidase, then measuring the released free SA with the biosensor. beta
      glucosidase treatment released more SA in acetate buffer extract than in Luria
      Bertani (LB) extract, while enzymatic hydrolysis in either solution released more
      free SA than acid hydrolysis. The biosensor-based method detected higher amounts
      of SA in pathogen-infected plants than did a GC/MS-based method. SA
      quantification of control and pathogen-treated wild-type and sid2 (SA induction
      deficient) plants demonstrated the efficacy of the method described. Using the
      methods detailed here, we were able to detect as little as 0.28 mug SA/g FW.
      Samples typically had a standard deviation of up to 25% of the mean. CONCLUSION:
      The ability of Acinetobacter sp. ADPWH_lux to detect SA in a complex mixture,
      combined with the enzymatic hydrolysis of SAG in crude extract, allowed the
      development of a simple, rapid, and inexpensive method to simultaneously measure
      free and glucose-conjugated SA. This approach is amenable to a high-throughput
      format, which would further reduce the cost and time required for biosensor-based
      SA quantification. Possible applications of this approach include
      characterization of enzymes involved in SA metabolism, analysis of temporal
      changes in SA levels, and isolation of mutants with aberrant SA accumulation.

PMID- 19117520
TI  - OxyGene: an innovative platform for investigating oxidative-response genes in
      whole prokaryotic genomes.
AB  - BACKGROUND: Oxidative stress is a common stress encountered by living organisms
      and is due to an imbalance between intracellular reactive oxygen and nitrogen
      species (ROS, RNS) and cellular antioxidant defence. To defend themselves against
      ROS/RNS, bacteria possess a subsystem of detoxification enzymes, which are
      classified with regard to their substrates. To identify such enzymes in
      prokaryotic genomes, different approaches based on similarity, enzyme profiles or
      patterns exist. Unfortunately, several problems persist in the annotation,
      classification and naming of these enzymes due mainly to some erroneous entries
      in databases, mistake propagation, absence of updating and disparity in function
      description. DESCRIPTION: In order to improve the current annotation of oxidative
      stress subsystems, an innovative platform named OxyGene has been developed. It
      integrates an original database called OxyDB, holding thoroughly tested anchor
      based signatures associated to subfamilies of oxidative stress enzymes, and a new
      anchor-driven annotator, for ab initio detection of ROS/RNS response genes. All
      complete Bacterial and Archaeal genomes have been re-annotated, and the results
      stored in the OxyGene repository can be interrogated via a Graphical User
      Interface. CONCLUSION: OxyGene enables the exploration and comparative analysis
      of enzymes belonging to 37 detoxification subclasses in 664 microbial genomes. It
      proposes a new classification that improves both the ontology and the annotation
      of the detoxification subsystems in prokaryotic whole genomes, while discovering
      new ORFs and attributing precise function to hypothetical annotated proteins.
      OxyGene is freely available at: http://www.umr6026.univ
      rennes1.fr/english/home/research/basic/software.

PMID- 19117521
TI  - Accuracy of drug advertisements in medical journals under new law regulating the
      marketing of pharmaceutical products in Switzerland.
AB  - BACKGROUND: New legal regulations for the marketing of pharmaceutical products
      were introduced in 2002 in Switzerland. We investigated whether claims in drug
      advertisements citing published scientific studies were justified by these
      studies after the introduction of these new regulations. METHODS: In this cross
      sectional study, two independent reviewers screened all issues of six major Swiss
      medical journals published in the year 2005 to identify all drug advertisements
      for analgesic, gastrointestinal and psychopharmacologic drugs and evaluated all
      drug advertisements referring to at least one publication. The pharmaceutical
      claim was rated as being supported, being based on a potentially biased study or
      not to be supported by the cited study according to pre-specified criteria. We
      also explored factors likely to be associated with supported advertisement
      claims. RESULTS: Of 2068 advertisements 577 (28%) promoted analgesic,
      psychopharmacologic or gastrointestinal drugs. Among them were 323 (56%)
      advertisements citing at least one reference. After excluding multiple
      publications of the same drug advertisement and advertisements with non
      informative references, there remained 29 unique advertisements with at least one
      reference to a scientific study. These 29 advertisements contained 78 distinct
      pairs of claims of analgesic, gastrointestinal and psychopharmacologic drugs and
      referenced studies. Thirty-seven (47%) claims were supported, 16 (21%) claims
      were not supported by the corresponding reference, and 25 (32%) claims were based
      on potentially biased evidence, with no relevant differences between drug groups.
      Studies with conflict of interest and studies stating industry funding were more
      likely to support the corresponding claim (RR 1.52, 95% CI 1.07-2.17 and RR 1.50,
      95% CI 0.98-2.28) than studies without identified conflict of interest and
      studies without information on type of funding. CONCLUSION: Following the
      introduction of new regulations for drug advertisement in Switzerland, 53% of all
      assessed pharmaceutical claims published in major medical journals are not
      supported by the cited referenced studies or based on potentially biased study
      information. In light of the discrepancy between the new legislation and the
      endorsement of these regulations, physicians should not trust drug advertisement
      claims even when they seem to refer to scientific studies.

PMID- 19117522
TI  - Human prostate supports more efficient replication of HIV-1 R5 than X4 strains ex
      vivo.
AB  - BACKGROUND: In order to determine whether human prostate can be productively
      infected by HIV-1 strains with different tropism, and thus represent a potential
      source of HIV in semen, an organotypic culture of prostate from men undergoing
      prostatic adenomectomy for benign prostate hypertrophy (BPH) was developed. The
      presence of potential HIV target cells in prostate tissues was investigated using
      immunohistochemistry. The infection of prostate explants following exposures with
      HIV-1 R5, R5X4 and X4 strains was analyzed through the measure of RT activity in
      culture supernatants, the quantification of HIV DNA in the explants and the
      detection of HIV RNA+ cells in situ. RESULTS: The overall prostate
      characteristics were retained for 21/2 weeks in culture. Numerous potential HIV-1
      target cells were detected in the prostate stroma. Whilst HIV-1 R5SF162 strain
      consistently productively infected prostatic T lymphocytes and macrophages, the
      prototypic X4IIIB strain and a primary R5X4 strain showed less efficient
      replication in this organ. CONCLUSION: The BPH prostate is a site of HIV-1 R5
      replication that could contribute virus to semen. A limited spreading of HIV-1 X4
      and R5X4 in this organ could participate to the preferential sexual transmission
      of HIV-1 R5 strains.

PMID- 19117523
TI  - Detergent resistant membrane-associated IDE in brain tissue and cultured cells:
      Relevance to Abeta and insulin degradation.
AB  - BACKGROUND: Insulin degrading enzyme (IDE) is implicated in the regulation of
      amyloid beta (Abeta) steady-state levels in the brain, and its deficient
      expression and/or activity may be a risk factor in sporadic Alzheimer's disease
      (AD). Although IDE sub-cellular localization has been well studied, the
      compartments relevant to Abeta degradation remain to be determined. RESULTS: Our
      results of live immunofluorescence, immuno gold electron-microscopy and gradient
      fractionation concurred to the demonstration that endogenous IDE from brain
      tissues and cell cultures is, in addition to its other localizations, a detergent
      resistant membrane (DRM)-associated metallopeptidase. Our pulse chase experiments
      were in accordance with the existence of two pools of IDE: the cytosolic one with
      a longer half-life and the membrane-IDE with a faster turn-over. DRMs-associated
      IDE co-localized with Abeta and its distribution (DRMs vs. non-DRMs) and activity
      was sensitive to manipulation of lipid composition in vitro and in vivo. When IDE
      was mis-located from DRMs by treating cells with methyl-beta-cyclodextrin
      (MbetaCD), endogenous Abeta accumulated in the extracellular space and exogenous
      Abeta proteolysis was impaired. We detected a reduced amount of IDE in DRMs of
      membranes isolated from mice brain with endogenous reduced levels of cholesterol
      (Chol) due to targeted deletion of one seladin-1 allele. We confirmed that a
      moderate shift of IDE from DRMs induced a substantial decrement on IDE-mediated
      insulin and Abeta degradation in vitro. CONCLUSION: Our results support the
      notion that optimal substrate degradation by IDE may require its association with
      organized-DRMs. Alternatively, DRMs but not other plasma membrane regions, may
      act as platforms where Abeta accumulates, due to its hydrophobic properties,
      reaching local concentration close to its Km for IDE facilitating its clearance.
      Structural integrity of DRMs may also be required to tightly retain insulin
      receptor and IDE for insulin proteolysis. The concept that mis-location of Abeta
      degrading proteases away from DRMs may impair the physiological turn-over of
      Abeta in vivo deserves further investigation in light of therapeutic strategies
      based on enhancing Abeta proteolysis in which DRM protease-targeting may need to
      be taken into account.

PMID- 19117524
TI  - Developing a national dissemination plan for collaborative care for depression:
      QUERI Series.
AB  - BACKGROUND: Little is known about effective strategies for disseminating and
      implementing complex clinical innovations across large healthcare systems. This
      paper describes processes undertaken and tools developed by the U.S. Department
      of Veterans Affairs (VA) Mental Health Quality Enhancement Research Initiative
      (MH-QUERI) to guide its efforts to partner with clinical leaders to prepare for
      national dissemination and implementation of collaborative care for depression.
      METHODS: An evidence-based quality improvement (EBQI) process was used to develop
      an initial set of goals to prepare the VA for national dissemination and
      implementation of collaborative care. The resulting product of the EBQI process
      is referred to herein as a "National Dissemination Plan" (NDP). EBQI participants
      included: a) researchers with expertise on the collaborative care model for
      depression, clinical quality improvement, and implementation science, and b) VA
      clinical and administrative leaders with experience and expertise on how to adapt
      research evidence to organizational needs, resources and capacity. Based on EBQI
      participant feedback, drafts of the NDP were revised and refined over multiple
      iterations before a final version was approved by MH-QUERI leadership. 'Action
      Teams' were created to address each goal. A formative evaluation framework and
      related tools were developed to document processes, monitor progress, and
      identify and act upon barriers and facilitators in addressing NDP goals. RESULTS:
      The National Dissemination Plan suggests that effectively disseminating
      collaborative care for depression in the VA will likely require attention to:
      Guidelines and Quality Indicators (4 goals), Training in Clinical Processes and
      Evidence-based Quality Improvement (6 goals), Marketing (7 goals), and
      Informatics Support (1 goal). Action Teams are using the NDP as a blueprint for
      developing infrastructure to support system-wide adoption and sustained
      implementation of collaborative care for depression. To date, accomplishments
      include but are not limited to: conduct of a systematic review of the literature
      to update VA depression treatment guidelines to include the latest evidence on
      collaborative care for depression; training for clinical staff on TIDES
      (Translating Initiatives for Depression into Effective Solutions project) care;
      spread of TIDES care to new VA facilities; and integration of TIDES depression
      assessment tools into a planned update of software used in delivery of VA mental
      health services. Thus far, common barriers encountered by Action Teams in
      addressing NDP goals include: a) limited time to address goals due to competing
      tasks/priorities, b) frequent turnover of key organizational
      leaders/stakeholders, c) limited skills and training among team members for
      addressing NDP goals, and d) difficulty coordinating activities across Action
      Teams on related goals. CONCLUSION: MH-QUERI has partnered with VA organizational
      leaders to develop a focused yet flexible plan to address key factors to prepare
      for national dissemination and implementation of collaborative care for
      depression. Early indications suggest that the plan is laying an important
      foundation that will enhance the likelihood of successful implementation and
      spread across the VA healthcare system.

PMID- 19117525
TI  - Patterns of knowledge and condom use among population groups: results from the
      2005 Ethiopian behavioral surveillance surveys on HIV.
AB  - BACKGROUND: Behavioral surveys help interpret the magnitude of HIV/AIDS. We
      analyzed indicators of knowledge on HIV/AIDS and condom use among sub populations
      selected for behavioral surveillance in Ethiopia. METHODS: We used 2005 HIV/AIDS
      behavioral data from ten target groups. These were female sex workers, defense
      forces, police force, pastoralists, truck drivers, intercity bus drivers, road
      construction workers, teachers, factory workers and people in ANC catchment
      areas. RESULTS: Data from 14,524 individuals were analyzed. The majority were
      males (63.6%). Overall, knowledge of the three preventive methods, misconceptions
      and comprehensive knowledge was 57%, 75% and 18.5%, respectively. Female sex
      workers and the defense force showed some behavioral change in using a condom
      during the most recent sexual encounter and consistently used a condom with non
      regular sexual partners and paying partners. Women, pastoralists and the
      illiterate were less likely to use condom. CONCLUSION: Misconceptions about the
      transmission of HIV were high and comprehensive knowledge about HIV & AIDS was
      low, particularly among pastoralists. Consistent condom use and condom use during
      the last sexual encounter were high among both female sex workers and defense
      force employees, both with paying and non-regular sexual partners. This might be
      a positive sign, though a considerable proportion in each target group did not
      report using a condom during sex with non-regular partners.

PMID- 19117526
TI  - Inhibition of HMG CoA reductase reveals an unexpected role for cholesterol during
      PGC migration in the mouse.
AB  - BACKGROUND: Primordial germ cells (PGCs) are the embryonic precursors of the
      sperm and eggs. Environmental or genetic defects that alter PGC development can
      impair fertility or cause formation of germ cell tumors. RESULTS: We demonstrate
      a novel role for cholesterol during germ cell migration in mice. Cholesterol was
      measured in living tissue dissected from mouse embryos and was found to
      accumulate within the developing gonads as germ cells migrate to colonize these
      structures. Cholesterol synthesis was blocked in culture by inhibiting the
      activity of HMG CoA reductase (HMGCR) resulting in germ cell survival and
      migration defects. These defects were rescued by co-addition of isoprenoids and
      cholesterol, but neither compound alone was sufficient. In contrast, loss of the
      last or penultimate enzyme in cholesterol biosynthesis did not alter PGC numbers
      or position in vivo. However embryos that lack these enzymes do not exhibit
      cholesterol defects at the stage at which PGCs are migrating. This demonstrates
      that during gestation, the cholesterol required for PGC migration can be supplied
      maternally. CONCLUSION: In the mouse, cholesterol is required for PGC survival
      and motility. It may act cell-autonomously by regulating clustering of growth
      factor receptors within PGCs or non cell-autonomously by controlling release of
      growth factors required for PGC guidance and survival.

PMID- 19117527
TI  - Perinatal HIV transmission and the cost-effectiveness of screening at 14 weeks
      gestation, at the onset of labour and the rapid testing of infants.
AB  - BACKGROUND: Preventing HIV transmission is a worldwide public health issue.
      Vertical transmission of HIV from a mother can be prevented with diagnosis and
      treatment, but screening incurs cost. The U.S. Virgin Islands follows the
      mainland policy on antenatal screening for HIV even though HIV prevalence is
      higher and rates of antenatal care are lower. This leads to many cases of
      vertically transmitted HIV. A better policy is required for the U.S. Virgin
      Islands. METHODS: The objective of this research was to estimate the cost
      effectiveness of relevant HIV screening strategies for the antenatal population
      in the U.S. Virgin Islands. An economic model was used to evaluate the
      incremental costs and incremental health benefits of nine different combinations
      of perinatal HIV screening strategies as compared to existing practice from a
      societal perspective. Three opportunities for screening were considered in
      isolation and in combination: by 14 weeks gestation, at the onset of labor, or of
      the infant after birth. The main outcome measure was the cost per life year
      gained (LYG). RESULTS: Results indicate that all strategies would produce
      benefits and save costs. Universal screening by 14 weeks gestation and screening
      the infant after birth is the recommended strategy, with cost savings of
      $1,122,787 and health benefits of 310 LYG. Limitations include the limited
      research on the variations in screening acceptance of screening based on specimen
      sample, race and economic status. The benefits of screening after 14 weeks
      gestation but before the onset of labor were also not addressed. CONCLUSION: This
      study highlights the benefits of offering screening at different opportunities
      and repeat screening and raises the question of generalizing these results to
      other countries with similar characteristics.

PMID- 19117528
TI  - "There's nothing I can't do--I just put my mind to anything and I can do it": a
      qualitative analysis of how children with chronic disease and their parents
      account for and manage physical activity.
AB  - BACKGROUND: This paper reports the findings of a South Australian qualitative,
      exploratory study of children and young people living with a chronic disease, and
      their perceptions and experiences of physical activity. The perceptions and
      experiences of their parents were also explored. The chronic diseases were type 1
      diabetes, asthma and cystic fibrosis. METHODS: Multiple qualitative data
      collection techniques were used to elicit the children and young people's
      perspectives and experiences of physical activity, including focus groups, maps,
      photos and 'traffic light posters'. The children's parents were interviewed
      separately to ascertain their views of their child's participation in physical
      activities. RESULTS: Children and young people described their active
      participation in a wide variety of physical activities including organised sports
      and play, but made very little mention of any negative influence or impact due to
      their disease. Their parents' stories described the diligent background planning
      and management undertaken to enable their child to participate in a wide range of
      physical activities. CONCLUSION: The results of this study suggest that for these
      children and young people, having a chronic disease was not perceived as a
      barrier to participation in organised sport and recreational activities. They
      were physically active and perceived themselves to be no different from their
      peers. Their positive beliefs were shared by their parents and the level of
      participation described was enabled by the high level of parental support and
      background planning involved in managing their child's health care needs.

PMID- 19117529
TI  - Stent angioplasty of narrowed portocaval shunt in Budd Chiari syndrome: a case
      report.
AB  - BACKGROUND: Hepatic vein thrombosis (Budd-Chiari Syndrome) is a rare disorder
      resulting from an obstruction to the outflow of blood from the liver. Early
      decompression is needed to prevent liver dysfunction and death. Radiological
      intervention includes angioplasty of stenosis and webs and the placement of
      transjugular intrahepatic portosystemic shunts (TIPPS). Side-to-side portacaval
      shunt (SSPCS) remains the gold standard for achieving good long-term results.
      CASE PRESENTATION: A 37-year old lady underwent side-to-side portacaval shunt for
      Budd Chiari syndrome. She had early shunt blockage and this was successfully
      treated with the placement of a metallic stent across the shunt. CONCLUSION: At
      five years, she remains asymptomatic, with normal liver functions, no ascites,
      and normal flow through the stent on Colour Doppler examination.

PMID- 19117531
TI  - DNA-PK: the means to justify the ends?
AB  - The DNA-dependent protein kinase (DNA-PK) is central to the process of
      nonhomologous end joining because it recognizes and then binds double strand
      breaks initiating repair. It has long been appreciated that DNA-PK protects DNA
      ends to promote end joining. Here we review recent work from our laboratories and
      others demonstrating that DNA-PK can regulate end access both positively and
      negatively. This is accomplished via distinct autophosphorylation events that
      result in opposing effects on DNA end access. Additional autophosphorylations
      that are both physically and functionally distinct serve to regulate kinase
      activity and complex dissociation. Finally, DNA-PK both positively and negatively
      regulates DNA end access to repair via the homologous recombination pathway. This
      has particularly important implications in human cells because of DNA-PK's
      cellular abundance.

PMID- 19117532
TI  - Thymic microenvironments for T-cell repertoire formation.
AB  - Functionally competent immune system includes a functionally competent T-cell
      repertoire that is reactive to foreign antigens but is tolerant to self-antigens.
      The repertoire of T cells is primarily formed in the thymus through positive and
      negative selection of developing thymocytes. Immature thymocytes that undergo
      V(D)J recombination of T-cell antigen receptor (TCR) genes and that express the
      virgin repertoire of TCRs are generated in thymic cortex. The recent discovery of
      thymoproteasomes, a molecular complex specifically expressed in cortical thymic
      epithelial cells (cTEC), has revealed a unique role of cTEC in cuing the further
      development of immature thymocytes in thymic cortex, possibly by displaying
      unique self-peptides that induce positive selection. Cortical thymocytes that
      receive TCR-mediated positive selection signals are destined to survive for
      further differentiation and are induced to express CCR7, a chemokine receptor.
      Being attracted to CCR7 ligands expressed by medullary thymic epithelial cells
      (mTEC), CCR7-expressing positively selected thymocytes relocate to thymic
      medulla. The medullary microenvironment displays another set of unique self
      peptides for trimming positively selected T-cell repertoire to establish self
      tolerance, via promiscuous expression of tissue-specific antigens by mTEC and
      efficient antigen presentation by dendritic cells. Recent results demonstrate
      that tumor necrosis factor (TNF) superfamily ligands, including receptor
      activating NF-kappaB ligand (RANKL), CD40L, and lymphotoxin, are produced by
      positively selected thymocytes and pivotally regulate mTEC development and thymic
      medulla formation.

PMID- 19117530
TI  - Cis-regulatory elements and epigenetic changes control genomic rearrangements of
      the IgH locus.
AB  - Immunoglobulin variable region exons are assembled from discontinuous variable
      (V), diversity (D), and joining (J) segments by the process of V(D)J
      recombination. V(D)J rearrangements of the immunoglobulin heavy chain (IgH) locus
      are tightly controlled in a tissue-specific, ordered and allele-specific manner
      by regulating accessibility of V, D, and J segments to the recombination
      activating gene proteins which are the specific components of the V(D)J
      recombinase. In this review we discuss recent advances and established models
      brought forward to explain the mechanisms underlying accessibility control of
      V(D)J recombination, including research on germline transcripts, spatial
      organization, and chromatin modifications of the immunoglobulin heavy chain (IgH)
      locus. Furthermore, we review the functions of well-described and potential new
      cis-regulatory elements with regard to processes such as V(D)J recombination,
      allelic exclusion, and IgH class switch recombination.

PMID- 19117533
TI  - Pathogenesis of myocarditis and dilated cardiomyopathy.
AB  - Myocarditis is a disease with a variable clinical presentation, ranging from
      asymptomatic to a fatal outcome. Among the recognized causes of myocarditis are
      mutations in multiple genes; infection by bacterial, rickettsial, mycotic,
      protozoan, and viral agents; and exposure to drugs, toxins, and alcohol. Some
      subtypes of myocarditis, such as giant cell myocarditis or eosinophilic
      necrotizing myocarditis, are suspected to be caused by an autoimmune
      inflammation. Several lines of evidence support the involvement of autoimmunity
      in myocarditis. These include the production of antibodies against relevant self
      antigens, the fact that myocarditis symptoms can be relieved by immunosuppressive
      therapy in some patients, and a co-occurrence of myocarditis with other
      autoimmune diseases. Most of the evidence that myocarditis is an autoimmune
      disease comes from animal models. In this chapter, we discuss coxsackievirus B3
      induced myocarditis and myosin-induced myocarditis as models of both viral and
      autoimmune inflammation in the heart. The latest advances in the study of
      autoimmunity have been concentrated on T helper cells, particularly the newly
      discovered subset, Th17 cells. Experimental autoimmune myocarditis (EAM), a mouse
      model of myocarditis induced by cardiac myosin, is partly an IL-17-driven
      disease. However, we have shown recently in IL-13 knockout mice that the disease
      can be driven through other pathways, and that the Th1 helper cells also lead to
      severe heart inflammation. Most importantly, IL-17A knockout mice are not fully
      protected against EAM and still develop mild myocarditis. The most abundant cells
      in heart infiltrate in human giant cell myocarditis or EAM are
      monocyte/macrophages, and there is now evidence that macrophages play a decisive
      role in the course of EAM.

PMID- 19117534
TI  - Emergence of the Th17 pathway and its role in host defense.
AB  - Recently, a paradigm shift has emerged in T-cell-mediated adaptive immunity. On
      the heels of the discovery of T cells with immunosuppressive function, so-called
      regulatory T cells (Tregs), the diversity of effector cells has expanded to
      include a third helper T cell, termed Th17. The appreciation that Th17 cells are
      products of a distinct effector pathway depended critically on observations made
      during investigations of mouse models of autoimmunity, advanced by discovery of
      the cytokines IL-17 and IL-23. These studies understandably led investigators to
      highlight the role played by Th17 cells in autoimmunity. Yet while the
      dysfunctional behavior of this phenotype as a contributor to inflammatory disease
      remains a central issue, this pathway evolved to meet a need for host protection
      against potential pathogens. It has become apparent that the Th17 pathway
      promotes host defense against certain extracellular bacteria and fungi, but more
      recent studies also implicate a role in protection against some protozoa and
      viruses. Here we review the experimental history that ultimately uncovered the
      existence and nature of Th17 cells, and then turn the reader's attention to what
      is currently known about Th17 cells as a bulwark against pathogens.

PMID- 19117535
TI  - Peptides presented in vivo by HLA-DR in thyroid autoimmunity.
AB  - The association of the major histocompatibility complex (MHC) genes with
      autoimmune diseases together with the ectopic expression of class II molecules by
      epithelial cells of the target tissue gives to these molecules a central role in
      the pathogenesis of the disease, in its regulation and in the persistence of the
      immune response in situ. HLA-DR molecules expressed by thyroid follicular cells
      in thyroid autoimmune diseases are compact molecules stably associated with
      peptides. The nature of these peptides is of vital importance in the
      understanding of the disease, since these MHC-II-peptide complexes are going to
      be recognized by both effector and regulatory T cells in situ. In this chapter,
      we review the current state of the analysis of naturally processed peptides
      presented by MHC class II molecules in the context of autoimmunity and we discuss
      our data of natural HLA-DR ligands eluted from Graves' disease affected thyroid
      glands, from where autoantigen-derived peptides have been identified.

PMID- 19117536
TI  - Treatment of mitochondrial diseases strengthening mitochondria by stimulating
      glycolysis with insulin.

PMID- 19117537
TI  - Knowledge transfer and practice change.

PMID- 19117538
TI  - Heavy breathing: energy conversion by mitochondrial respiratory supercomplexes.
AB  - The phrase "respiratory chain" implies that energy that is ultimately derived
      from mitochondrial oxidative phosphorylation is produced via a linear arrangement
      of discrete electron transfer complexes. A recent paper in Molecular Cell (Acin
      Perez et al., 2008) calls this model into question.

PMID- 19117539
TI  - Models use leptin and calculus to count calories.
AB  - Thermostats have "set-points" that engineers design with mathematical rigor. Work
      in this issue of Cell Metabolism (Tam et al., 2009) applies similar modeling
      strategies to explore the control of murine energy and body weight homeostasis by
      leptin.

PMID- 19117540
TI  - The liver--a potential new player in islet regeneration?
AB  - Pancreatic islet beta cell mass expands in response to certain physiological
      conditions such as pregnancy and obesity, but the signaling pathways involved are
      not well understood. Possible insights come from a newly described regulatory
      circuit through which obesity-enhanced kinase signaling in the liver triggers
      expansion of islet mass and enhanced insulin secretion.

PMID- 19117541
TI  - Branching out on AMPK Regulation.
AB  - AMP-activated protein kinase (AMPK) regulates cellular metabolism in response to
      available energy at both the cellular and whole-body levels. In this issue,
      McBride et al. (2009) show that AMPK is inhibited by glycogen, adding another
      tier to its regulation and suggesting that it can act as a glycogen sensor.

PMID- 19117542
TI  - Structure of full-length PPARgamma-RXRalpha: a snapshot of a functional complex?
AB  - The first crystal structure of a full-length nuclear receptor complex on DNA
      reveals an interdomain contact between the ligand- and DNA-binding domains of
      subunits and illuminates the role of the 5' extension of the binding site in
      polarity of positioning. These findings have possible functional implications.

PMID- 19117543
TI  - Oxygen sensors at the crossroad of metabolism.
AB  - Aerobic organisms developed mechanisms to protect themselves against a shortage
      of oxygen (O(2)). Recent studies reveal that O(2) sensors, belonging to the novel
      class of 2-oxoglutarate dependent iron(ii)-dioxygenases, have more important
      roles in metabolism than anticipated. Here, we provide a "metabolo-centric"
      overview of the role of the PHD/FIH members of this family in metabolism, in
      particular on how they regulate O(2) supply and consumption, energy compensation
      and conservation, O(2) conformance and hypoxia tolerance, redox and pH
      homeostasis, and other vital metabolic processes with implications in health and
      disease. These insights may offer novel opportunities for the treatment of
      ischemic diseases.

PMID- 19117544
TI  - The glycogen-binding domain on the AMPK beta subunit allows the kinase to act as
      a glycogen sensor.
AB  - AMPK beta subunits contain a conserved domain that causes association with
      glycogen. Although glycogen availability is known to affect AMPK regulation in
      vivo, the molecular mechanism for this has not been clear. We now show that AMPK
      is inhibited by glycogen, particularly preparations with high branching content.
      We synthesized a series of branched oligosaccharides and show that those with a
      single alpha1-->6 branch are allosteric inhibitors that also inhibit
      phosphorylation by upstream kinases. Removal of the outer chains of glycogen
      using phosphorylase, thus exposing the outer branches, renders inhibition of AMPK
      more potent. Inhibition by all carbohydrates tested was dependent on the glycogen
      binding domain being abolished by mutation of residues required for carbohydrate
      binding. Our results suggest the hypothesis that AMPK, as well as monitoring
      immediate energy availability by sensing AMP/ATP, may also be able to sense the
      status of cellular energy reserves in the form of glycogen.

PMID- 19117545
TI  - Endoplasmic reticulum stress plays a central role in development of leptin
      resistance.
AB  - Leptin has not evolved as a therapeutic modality for the treatment of obesity due
      to the prevalence of leptin resistance in a majority of the obese population.
      Nevertheless, the molecular mechanisms of leptin resistance remain poorly
      understood. Here, we show that increased endoplasmic reticulum (ER) stress and
      activation of the unfolded protein response (UPR) in the hypothalamus of obese
      mice inhibits leptin receptor signaling. The genetic imposition of reduced ER
      capacity in mice results in severe leptin resistance and leads to a significant
      augmentation of obesity on a high-fat diet. Moreover, we show that chemical
      chaperones, 4-phenyl butyric acid (PBA), and tauroursodeoxycholic acid (TUDCA),
      which have the ability to decrease ER stress, act as leptin-sensitizing agents.
      Taken together, our results may provide the basis for a novel treatment of
      obesity.

PMID- 19117546
TI  - A mathematical model of murine metabolic regulation by leptin: energy balance and
      defense of a stable body weight.
AB  - We have developed a physiologically based mathematical model, with parameters
      derived from published experimental data, to simulate the regulatory effects of
      the leptin pathway on murine energy homeostasis. Model outcomes are consistent
      with data reported in the literature and reproduce key characteristics of the
      energy regulatory system, including compensatory responses that counteract
      changes in body weight and the failure of this ability when the leptin pathway is
      disrupted. Our model revealed the possibility of multiple steady states for body
      weight. It also provided a unified theoretical framework for two historically
      antagonistic hypotheses regarding body weight regulation ("set-point" versus
      "settling point"). Finally, our model has identified potential avenues for future
      investigations.

PMID- 19117547
TI  - Enhanced orexin receptor-2 signaling prevents diet-induced obesity and improves
      leptin sensitivity.
AB  - The hypothalamic orexin neuropeptide acutely promotes appetite, yet orexin
      deficiency in humans and mice is associated with obesity. Prolonged effects of
      increased orexin signaling upon energy homeostasis have not been fully
      characterized. Here, we examine the metabolic effects of orexin gain of function
      utilizing genetic and pharmacologic techniques in mice. Transgenic orexin
      overexpression confers resistance to high-fat diet-induced obesity and insulin
      insensitivity by promoting energy expenditure and reducing consumption. Genetic
      studies indicate that orexin receptor-2 (OX2R), rather than OX1R signaling,
      predominantly mediates this phenotype. Likewise, prolonged central administration
      of an OX2R-selective peptide agonist inhibits diet-induced obesity. While orexin
      overexpression enhances the anorectic-catabolic effects of central leptin
      administration, obese leptin-deficient mice are completely resistant to the
      metabolic effects of orexin overexpression or OX2R agonist infusion. We conclude
      that enhanced orexin-OX2R signaling confers resistance to diet-induced features
      of the metabolic syndrome through negative energy homeostasis and improved leptin
      sensitivity.

PMID- 19117548
TI  - The nuclear orphan receptor COUP-TFII plays an essential role in adipogenesis,
      glucose homeostasis, and energy metabolism.
AB  - Adipose tissue development and function play a central role in the pathogenesis
      and pathophysiology of metabolic syndromes. Here, we show that chicken ovalbumin
      upstream promoter transcription factor II (COUP-TFII) plays a pivotal role in
      adipogenesis and energy homeostasis. COUP-TFII is expressed in the early stages
      of white adipocyte development. COUP-TFII heterozygous mice (COUP-TFII(+/-)) have
      much less white adipose tissue (WAT) than wild-type mice (COUP-TFII(+/+)). COUP
      TFII(+/-) mice display a decreased expression of key regulators for WAT
      development. Knockdown COUP-TFII in 3T3-L1 cells resulted in an increased
      expression of Wnt10b, while chromatin immunoprecipitation analysis revealed that
      Wnt10b is a direct target of COUP-TFII. Moreover, COUP-TFII(+/-) mice have
      increased mitochondrial biogenesis in WAT, and COUP-TFII(+/-) mice have improved
      glucose homeostasis and increased energy expenditure. Thus, COUP-TFII regulates
      adipogenesis by regulating the key molecules in adipocyte development and can
      serve as a target for regulating energy metabolism.

PMID- 19117549
TI  - The Pro12Ala PPARgamma2 variant determines metabolism at the gene-environment
      interface.
AB  - The metabolic impact of the common peroxisome proliferator-activated receptor
      gamma isoform 2 (PPARgamma2) variant Pro12Ala in human populations has been
      widely debated. We demonstrate, using a Pro12Ala knockin model, that on chow
      diet, Ala/Ala mice are leaner, have improved insulin sensitivity and plasma lipid
      profiles, and have longer lifespans. Gene-environment interactions played a key
      role as high-fat feeding eliminated the beneficial effects of the Pro12Ala
      variant on adiposity, plasma lipids, and insulin sensitivity. The underlying
      molecular mechanisms involve changes in cofactor interaction and adiponectin
      signaling. Altogether, our results establish the Pro12Ala variant of Ppargamma2
      as an important modulator in metabolic control that strongly depends on the
      metabolic context.

PMID- 19117550
TI  - Hypoxia-independent angiogenesis in adipose tissues during cold acclimation.
AB  - The molecular mechanisms of angiogenesis in relation to adipose tissue metabolism
      remain poorly understood. Here, we show that exposure of mice to cold led to
      activation of angiogenesis in both white and brown adipose tissues. In the
      inguinal depot, cold exposure resulted in elevated expression levels of brown-fat
      associated proteins, including uncoupling protein-1 (UCP1) and PGC-1alpha.
      Proangiogenic factors such as VEGF were upregulated, and endogenous angiogenesis
      inhibitors, including thrombospondin, were downregulated. In wild-type mice, the
      adipose tissues became hypoxic during cold exposure; in UCP1(-/-) mice, hypoxia
      did not occur, but, remarkably, the augmented angiogenesis was unaltered and was
      thus hypoxia independent. Intriguingly, VEGFR2 blockage abolished the cold
      induced angiogenesis and significantly impaired nonshivering thermogenesis
      capacity. Unexpectedly, VEGFR1 blockage resulted in the opposite effects:
      increased adipose vascularity and nonshivering thermogenesis capacity. Our
      findings have conceptual implications concerning application of angiogenesis
      modulators for treatment of obesity and metabolic disorders.

PMID- 19117551
TI  - Dental caries, tooth wear and diet in an adult medieval (12th-14th century)
      population from mediterranean France.
AB  - OBJECTIVES: The aims of the present work were to determine the frequency and
      distribution of caries and tooth wear on paired maxillae of a mediaeval sample
      from southwest France in which the sex of the remains had been established, and
      to make a relation with the diet of this population. MATERIALS AND METHODS: The
      sample analysed consisted of the dental remains of 58 adult individuals (29 men
      and 29 women) excavated from the mediaeval cemetery of the archaeological site of
      Vilarnau d'Amont (southwest France). A total of 1395 teeth were examined.
      RESULTS: The frequency of ante-mortem tooth loss for the sample was 8.7% and the
      frequency of caries was 17.5%. The frequencies of carious lesions in adult men
      and women's dentition were 21.9% and 14.0%. The most frequent were occlusal
      (49.7% and 34.3%) and approximal caries (26.5% and 37.4%). Concerning tooth wear,
      all 58 individuals were affected by attrition (100%) and more than 90% of the
      teeth were concerned. Most of them showed the presence of dentin clusters. There
      was no significant difference between men and women for caries and tooth wear.
      DISCUSSION: These findings are similar to those of other studies on European
      populations of the same socio-economic status and confirm the predominance of
      tooth wear over carious lesions during this period. Both caries and tooth wear
      may be related to the regional diet of this rural population.

PMID- 19117552
TI  - Do anxious parents interpretive biases towards threat extend into their child's
      environment?
AB  - Anxiety disorders are known to run in families [Turner, S. M., Beidel, D. C., &
      Costello, A. (1987). Psychopathology in the offspring of anxiety disorder
      patients. Journal of Consulting and Clinical Psychology, 55(2), 229-235] and
      environmental factors may largely account for the concordance between parental
      and child anxieties. Cognitive psychology models emphasise the importance of
      interpretive biases towards threat in the maintenance of anxiety and it is well
      established that anxious adults and children display similar interpretive biases
      and that these biases in anxious parents and their children are correlated. This
      raises the question of whether anxious cognitions/cognitive style may be
      transmitted from parent to child. We propose that this is more likely if anxious
      parents demonstrate interpretive biases not only about potential threats in their
      own environment but also about potential threats in their child's environment.
      Forty parents completed a recognition memory measure of interpretation bias
      adapted from Eysenck, Mogg, May, Richards, and Mathews (1991) [Bias in
      interpretation of ambiguous sentences related to threat in anxiety. Journal of
      Abnormal Psychology, 100(2), 144-150] to measure biases in response to
      potentially threat provoking situations involving themselves and their child. The
      interpretive biases demonstrated by parents were similar across situations
      involving themselves and their children. As expected, parental interpretive
      biases were further modified by anxiety with higher levels of parental anxiety
      associated with more negative interpretive biases about situations in their own
      and their child's environment, although this association was significantly
      stronger for potentially threat provoking situations in their own environment.
      These results are consistent with parent's interpretive biases extending beyond
      their own environment into their child's environment, although future research
      should continue to consider the mechanisms by which anxious parents may transmit
      fear cognitions to their children.

PMID- 19117553
TI  - Structure of the O-antigen of Yersinia pseudotuberculosis O:4a revised.
AB  - The O-specific polysaccharide was isolated by mild acid degradation of the
      lipopolysaccharide of Yersinia pseudotuberculosis O:4a and studied by NMR
      spectroscopy, including 2D ROESY and (1)H, (13)C HMBC experiments. The following
      structure of the pentasaccharide repeating unit of the polysaccharide was
      established, which differs from the structure reported earlier [Gorshkova, R. P.
      et al., Bioorg. Khim. 1983, 9, 1401-1407] in the linkage modes between the
      monosaccharides: [carbohydrate sequence see in text] where Tyv stands for 3,6
      dideoxy-D-arabino-hexose (tyvelose). The structure of the Y. pseudotuberculosis
      O:4a antigen resembles that of Y. pseudotuberculosis O:2c, which differs in the
      presence of abequose (3,6-dideoxy-D-xylo-hexose) in place of tyvelose only.

PMID- 19117554
TI  - Writing about mirror writing.

PMID- 19117556
TI  - A 6-year review of total parenteral nutrition use and association with late-onset
      acute respiratory distress syndrome among ventilated trauma victims.
AB  - AIM: To establish whether total parenteral nutrition (TPN) for ventilated trauma
      victims is associated with late-onset acute respiratory distress syndrome (ARDS)
      independent of ventilation and transfusion parameters. METHOD: Intensive care
      unit data over 6 years from a level I centre regarding all trauma victims > or =
      16 years old who underwent mechanical ventilation within the first 48 h of
      admission were examined. Patients were prospectively followed for late ARDS.
      Variables were examined for significant changes over time and independent
      associations with late ARDS were determined. RESULTS: Of 2346 eligible patients
      among whom 404 (17.2%) were exposed to TPN, 192 (8.2%) met criteria for late
      ARDS. The incidence of late ARDS among those exposed to TPN was 28.7% (116/404)
      compared with 3.9% (76/1942) among those not so exposed. Adjustments for
      potential confounding associated risk factors were made. CONCLUSIONS: TPN
      administration is independently associated with late ARDS, and its use among
      critically ill trauma victims should be carefully scrutinised.

PMID- 19117555
TI  - Examination of the relationships between environmental exposures to volatile
      organic compounds and biochemical liver tests: application of canonical
      correlation analysis.
AB  - This study was to explore the relationships between personal exposure to 10
      volatile organic compounds (VOCs) and biochemical liver tests with the
      application of canonical correlation analysis. Data from a subsample of the 1999
      2000 National Health and Nutrition Examination Survey were used. Serum albumin,
      total bilirubin (TB), alanine aminotransferase (ALT), aspartate aminotransferase
      (AST), lactate dehydrogenase (LDH), alkaline phosphatase (ALP), and gamma
      glutamyl transferase (GGT) served as the outcome variables. Personal exposures to
      benzene, chloroform, ethylbenzene, tetrachloroethene, toluene, trichloroethene, o
      xylene, m-,p-xylene, 1,4-dichlorobenzene, and methyl tert-butyl ether (MTBE) were
      assessed through the use of passive exposure monitors worn by study participants.
      The first two canonical correlations were 0.3218 and 0.2575, suggesting a
      positive correlation mainly between the six VOCs (benzene, ethylbenzene, toluene,
      o-xylene, m-,p-xylene, and MTBE) and the three biochemical liver tests (albumin,
      ALP, and GGT) and a positive correlation mainly between the two VOCs (1,4
      dichlorobenzene and tetrachloroethene) and the two biochemical liver tests (LDH
      and TB). Subsequent multiple linear regressions show that exposure to benzene,
      toluene, or MTBE was associated with serum albumin, while exposure to
      tetrachloroethene was associated with LDH and total bilirubin. In conclusion,
      exposure to certain VOCs as a group or individually may influence certain
      biochemical liver test results in the general population.

PMID- 19117557
TI  - Repeated successful anaesthesia in a 110-year old.

PMID- 19117558
TI  - 30 years of polytrauma care: An analysis of the change in strategies and results
      of 4849 cases treated at a single institution.
AB  - The quality and progress of treatment of 4849 multiple trauma patients treated at
      one institution was reviewed retrospectively. Three periods, 1975-1984 (decade I;
      n=1469) and 1985-1994 (decade II; n=1937) and 1995-2004 (decade III; n=1443) were
      compared. 65% of multiple trauma patients had cerebral injuries, 58% thoracic
      trauma and 81% extremity fractures (37% open injuries). Injury combinations
      decreased during all decades with head/extremity injuries being the most common
      combination. Throughout the three decades pre-hospital care became more
      aggressive with an increase of intravenous fluid resuscitation (I: 80%, II: 97%,
      III: 98%). Chest tube insertion decreased after an initial increase (I: 41%, II:
      83%, III: 27%) as well as intubation (I: 82%, II: 94%, III: 59%). Rescue times
      were progressively shortened. For initial clinical diagnosis of massive abdominal
      haemorrhage ultrasound (I: 17%, II: 92%, III: 97%) replaced peritoneal lavage (I:
      44%, II: 28%, III: 0%). CT-scans were used more frequently for the initial
      diagnosis of head injuries and other injuries to the trunk throughout the
      observation time. With regard to complications, acute renal failure decreased by
      half (I: 8.4%; II: 3.7%; III: 3.9%), ARDS initially decreased but increased again
      in the last decade (I: 18.1%, II: 13.4%, III: 15.3%), whereas the rate of
      multiple organ dysfunction syndrome (MODS) increased continuously (I: 14.2%, II:
      18.9%, III: 19.8%) probably due to a decline of the mortality rate from 37% in
      the first to 22% in the second and 18% in the third decade and parallel increase
      of the time of death. These treatment results summarise the enormous clinical
      effort as well as medical progress in polytrauma management over the past 30
      years. Further reduction of mortality is desirable, but probably only possible
      when immediate causal therapy of later posttraumatic organ failure can be
      established.

PMID- 19117559
TI  - The role of erythropoietin in the acute phase of trauma management: evidence
      today.
AB  - Trauma patients often present in a state of haemorrhagic shock. Blood products
      remain the gold standard of resuscitation, but allogeneic blood transfusions
      (ABTs) are associated with several risks. The stimulating effect of recombinant
      erythropoietin (EPO-A) on erythropoiesis has raised interest in its
      administration as an alternative. The existing evidence on the early use of EPO-A
      in the acute phase of trauma patients management consists of only 14
      publications. The level of evidence of these studies and the number of treated
      patients was not found to be adequate to support its generalised use, despite
      their favourable results. Its safety profile, the preliminary proofs of its
      efficacy, and the additional cyto-protective properties of EPO-A strongly
      encourage further controlled studies assessing its use in the acute setting of
      initial trauma management.

PMID- 19117560
TI  - The evolution of the diagnostic work-up for stab wounds to the back and flank.
AB  - BACKGROUND: Stab wounds to the back and flank infrequently cause injuries
      requiring operative treatment. Triple-contrast CT scan (3CT) has essentially
      replaced diagnostic peritoneal lavage (DPL) as the primary means of identifying
      patients who require operative intervention. This study aims to review the
      evolution of the diagnostic work-up for stab wounds to the back and flank.
      METHODS: We performed a retrospective review of haemodynamically stable patients
      with stab wound to the back or flank treated at a single Level 1 trauma centre
      over a 10-year period. Diagnostic accuracy of DPL and 3CT screening tests were
      evaluated against the patient's subsequent clinical course. The elapsed time
      between emergency department (ED) presentation and test results was recorded and
      compared. RESULTS: A total of 177 patients were identified. 76 patients had stab
      wounds isolated to the back, 90 had stab wounds isolated to the flank and 11 had
      wounds in both locations. CT ultimately became the predominant initial diagnostic
      test during the study period. Although less frequently used over time, DPL
      retained good sensitivity and specificity for injuries requiring operative
      intervention (92% and 83%, respectively). 3CT identified all injuries requiring
      laparotomy (100% sensitivity) and had a specificity of 96%. 3CT was a more time
      consuming process, with results available at a median of 3:31h after arrival to
      the ED, as compared to 1:03h for DPL (p<0.01). CONCLUSIONS: 3CT diagnosed all
      injuries requiring operative intervention, and its use was associated with a
      lower rate of non-therapeutic laparotomies. However, average time to diagnosis by
      3CT was prolonged compared to DPL. Although 3CT has become the predominant
      diagnostic test when evaluating patients with stab wounds to the back and flank
      at our institution, efforts to further expedite the diagnostic work-up are
      necessary.

PMID- 19117561
TI  - Delayed pneumothorax after stab wound to thorax and upper abdomen: Truth or myth?
AB  - BACKGROUND: Stab wounds to the thorax and upper abdomen have the potential to
      cause pneumothorax (PTX). When a CXR (CXR) obtained during initial resuscitation
      is negative, a second CXR (CXR-2) is commonly performed with the goal of
      identifying delayed PTX. OBJECTIVES: To assess the diagnostic yield of the CXR-2
      in identifying delayed PTX. METHODS: Prospective observational study of patients
      (age >or=13 years) with stab wounds to the thorax (chest/back) and upper abdomen
      with suspected PTX, in a level 1 trauma centre. Patients were included if they
      had a negative initial CXR followed by a repeat CXR 3-6h after the initial one.
      EXCLUSION CRITERIA: patients who died, were transferred out of the ED, or
      received chest tubes before the second CXR. The outcome of interest was delayed
      PTX. All CXR were read by an attending radiologist. To test the inter-observer
      agreement, another blinded radiologist reviewed 20% of CXR. Continuous data is
      presented as mean+/-standard deviation and categorical data as percentages with
      95% confidence interval (CI). Kappa statistics were used to measure the inter
      observer agreement between radiologists. RESULTS: Between January 2003 and
      December 2006 a total of 185 patients qualified for the enrollment (mean age:
      28+/-10 years, age range: 13-65, 94% male). Only 2 patients (1.1%, 95% CI, 0.4-
      4.1%) had PTX on the CXR-2. Both patients received chest tubes. The inter
      observer agreement for radiology reports was high (kappa: 0.79). CONCLUSION:
      Occurrence of delayed PTX in patients with stab wounds to the thorax and upper
      abdomen and negative triage CXR is rare.

PMID- 19117562
TI  - Improved trauma patient outcomes after implementation of a dedicated trauma
      admitting service.
AB  - BACKGROUND: Regionalised trauma systems have been shown to improve the outcome of
      seriously injured patients. However, it is not clear which components of these
      systems have the most impact on patient outcomes. The study evaluates the
      association between implementation of a single, dedicated trauma admitting
      service at an urban trauma centre and subsequent patient outcomes. METHODS: This
      was a retrospective review of prospectively collected trauma registry data at the
      St George Public Hospital, a level I urban trauma centre in Sydney, Australia.
      Two concurrent 18-month periods, before and after implementation of a full-time
      trauma service, were compared for differences in patient mortality, complication
      rates, and ED, ICU and hospital lengths of stay. RESULTS: There were 962 patients
      admitted to the hospital in the 18 months immediately preceding the
      implementation of the trauma service (the PRE group) and 990 patients in the
      subsequent 18 months (the POST group). There were no significant differences
      between groups with respect to patient demographics or mechanism of injury,
      although a higher proportion of patients in the POST group had injury severity
      scores (ISS) above 15 (30.6% versus 24.8%, p=0.02). There was an 8% reduction in
      death rate among the most severely injured patients (ISS>15), in the POST group
      as compared to the PRE group (12.2% and 20.2% respectively, p=0.007).
      CONCLUSIONS: The implementation of a full-time trauma service in this hospital
      was associated with a reduction in death rate among the most severely injured
      patients, and a decrease in LOS in patients with an ISS<15.

PMID- 19117563
TI  - Quantifying the amount of padding improves the comfort and function of a
      fibreglass below-elbow cast.
AB  - AIM: To determine the quantity of cotton underpadding needed for a comfortable,
      functional, below-elbow fibreglass cast. METHODS: In this randomised,
      prospective, crossover, clinical trial, 45 people with minimally displaced distal
      radial fractures were enrolled to randomly receive, 14 days after injury, a
      fibreglass below-elbow cast with either two or four layers of cotton
      underpadding. The characteristics of the recipients were recorded. After 2 weeks
      of immobilisation, participants completed a numerical survey evaluating
      parameters of comfort and underwent clinical and radiographic assessment. They
      then crossed over to receive the other fibreglass cast design, the process was
      repeated, and they indicated their cast preference, if any. RESULTS: Of 37 people
      who completed the study, 20 preferred the two-layer model, 13 the four-layer
      model and 4 had no preference. No significant trend for one design over the other
      was shown (p=0.1), nor any statistical association between preference and
      participant characteristics or the order in which cast models were received.
      CONCLUSIONS: Participants did state a preference, but this was not related to
      recipient characteristics. Neither cast design was significantly the more
      comfortable; and both models were safe and functionally satisfactory.

PMID- 19117564
TI  - The injury profile after the 2008 earthquakes in China.
AB  - The 8.0 magnitude earthquake that struck China on May 12, 2008, was the deadliest
      earthquake in 30 years. Most hospitals were destroyed and limited facilities were
      available for medical service in the earthquake regions. Over the first 5 days,
      three general hospitals and one children's hospital admitted 1770 injured
      individuals. METHODS: We retrospectively collected data on 1770 injured subjects
      in three general hospitals (n=1723) and one children's hospital (n=47) in the
      quake-area during the first 5 days after the event. The diagnosis for the
      injuries was based on the final hospital diagnosis made by the physicians and
      classified by two-independent researchers using the International Statistical
      Classification of Diseases and Related Health Problems ICD-10 (WHO ICD-10
      Code.1993). To ensure the accuracy of the information, any questionable data was
      reviewed by phone with hospital staff. RESULTS: In three general hospitals, 848
      patients (48%) were male and 922 (52%) were female. Nine percent (n=84) of
      females and 8.8% (n=75) of males were over the age of 75. Four (0.4%) females and
      5 (0.5%) males were less than 1-year old. The most common injuries were the
      injuries of the knee, lower leg, ankle and foot (36%), followed by head injuries
      (18%). In the children's hospital, 31 (65%) of the patients were males and 16
      (35%) were females. 40% of the subjects were 10-14, while 21% were less than 1
      year old. The most frequently seen injuries were also of the knee, lower leg,
      ankle or foot (19%), and of the abdomen, lower back, lumbar spine and pelvis, and
      hip and thigh (15%). CONCLUSIONS: We gathered information from resources in
      Chinese, which at the time contained more records on this event than any
      documents in English. The age of the patients ranged from 7 days to 84 years old.
      Subjects over age 75 and children between 10 and 14 were the largest population
      in their respective hospitals, indicating that these groups required the greatest
      medical resources. The injury profile presented here serves as a reference not
      only for present injury intervention but also for future earthquake disaster
      response.

PMID- 19117565
TI  - Factors affecting anatomical region of injury, severity, and mortality for road
      trauma in a high-income developing country: lessons for prevention.
AB  - OBJECTIVES: To study the factors affecting anatomical region of injury, severity,
      and mortality among road users in United Arab Emirates so as to improve
      preventive measures. METHODS: Data of the Trauma Registry of Al Ain city were
      collected prospectively over 3 years (2003-2006) at the main trauma hospital. For
      traffic injuries, the following were assessed: gender, nationality, road user
      type, anatomical region(s) of injury, systolic blood pressure on admission,
      Glasgow Coma Scale (GCS), Injury Severity Score (ISS), and mortality. Analysis
      included frequencies, cross-tabulations, and logistic regression. RESULTS: There
      were 1070 patients, 89% male, 25% UAE nationals, and with a mean age of 31 years.
      Expatriates, mainly from non-Arabic speaking, low-income countries, accounted for
      88% of injured pedestrians, whilst nationals were overrepresented among vehicle
      occupants (29%), and motorcyclists 37%. Injuries of the extremities and head were
      frequent among pedestrians, motorcyclists, and bicyclists, whilst head and spine
      injuries were most common among front and rear vehicle occupants and drivers. The
      median ISS was five for pedestrians and four for all other road user types,
      including rear vehicle occupants. The mean hospitalisation was 9.7 days; 13% of
      patients were admitted to ICU with mean stay of 6.5 days. Overall mortality was
      4%; pedestrians accounted for 61% of deaths. Predictors of mortality were GCS
      (p<0.001), ISS (p<0.01) and systolic blood pressure on admission (p<0.03).
      CONCLUSIONS: Head injury was a major factor affecting mortality, followed by
      injury severity and hypotension. To reduce injury incidence and severity,
      legislation and education are needed to ensure use of seat belts by all vehicle
      occupants including rear passengers, high-visibility devices by other road users,
      helmets by motorcyclists and bicyclists, protective clothing and boots for
      motorcyclists, and traffic engineering for pedestrians.

PMID- 19117566
TI  - Venous glucose and arterial lactate as biochemical predictors of mortality in
      clinically severely injured trauma patients--a comparison with ISS and TRISS.
AB  - BACKGROUND: Early assessment of injury severity is important in trauma. Trauma
      scores are calculated after the fact and are useful for audit and research, but
      not in the emergency clinical setting. Glucose metabolism is altered in trauma,
      and we hypothesised that alterations in glucose and lactate levels would be an
      early predictor of mortality. METHODS: Review of trauma registry data identified
      1197 patients between May 2000 and September 2006 who had a trauma-team call out.
      Data collected included trauma scores, venous glucose (gluc), and arterial
      lactate (lact) on arrival. The predictive value of these variables was compared
      by ROC curves. RESULTS: The mortality rate for patients with gluc >11.0mmol/L was
      13.4% compared to 1.8% in those with gluc <or=11.0mmol/L (p<0.0001). Gluc had a
      specificity of 93.2% and a sensitivity of 37.9% for death. 13.0% of patients with
      lact >2.0mmol/L died, versus 2.7% with lact <or=2.0mmol/L, (p0.0003, specificity
      56.8% and sensitivity 81.0%). Glucose was the better biochemical predictor of
      mortality compared to lactate (ROC area 0.845 and 0.716, respectively). The TRISS
      (trauma and injury severity score) was a very accurate predictor (ROC 0.963),
      whereas the ISS (injury severity score) significantly less so (ROC 0.854). There
      was a significant correlation between gluc, ISS, and TRISS (p 0.01), as well as
      lactate and ISS (p 0.01). CONCLUSION: Glucose and lactate can predict mortality
      in severe trauma. The predictive value of glucose is comparable to that of ISS,
      and can be more easily employed in the clinical setting.

PMID- 19117567
TI  - Nursing sensitive quality indicators for nursing home care: international review
      of literature, policy and practice.
AB  - OBJECTIVES: To review nursing sensitive indicators used for nursing home care
      across seven nations with similar elder care (USA, Australia, Norway, New
      Zealand, England, Sweden and Denmark), and to evaluate their validity. DESIGN:
      Systematic search in the literature and other sources to find descriptions of
      development and validity testing of national quality indicators. DATA SOURCES:
      Papers from scientific databases, relevant websites, additional papers and
      reports, and personal communication with experts in the field. The material was
      included if it contributed to the description of each country's processes in
      defining nursing sensitive quality indicators for nursing home care, and the main
      focus was use, developing and/or testing of quality. REVIEW METHODS: An overview
      of each country's utilization of nursing sensitive quality indicators was
      obtained. The evidence for the validity in development and testing procedures was
      analyzed using a set of evaluation criteria. RESULTS: All countries, except
      Sweden, have nationally standardized assessment of the patient before admission
      to the nursing home. There is large variation in the way these data collection
      tools were developed and how the data is used. Only the USA has systematically
      developed quality indicators on the basis of resident assessments. Twenty-three
      indicators used nationally in USA, thirteen in Australia, four in Norway, three
      in New Zealand and three in England were selected for review, and were evaluated
      for their validity as described in the literature. All selected indicators had
      satisfactory face validity, and for the twenty-three indicators used in the USA
      there was evidence for reliability testing. None of the quality indicators met
      all the criteria for validity. Evidence that the quality indicators can
      demonstrate meaningful differences in care and that the information can be
      extracted with minimal extra efforts was not found. Thresholds for high or low
      quality were determined only for the US quality indicators. CONCLUSIONS: There
      are concerns about the validity and reliability of nursing sensitive quality
      indicators for nursing home care. The indicator development is sparsely
      documented. It is recommended that the development of quality indicators follows
      a sound process and that extensive empirical testing of the indicators is done.

PMID- 19117568
TI  - The postmodernist war on evidence-based practice.
AB  - In this paper, we examine the war of words between those who contend that health
      care practice, including nursing, should primarily be informed by research (the
      evidence-based practice movement), and those who argue that there should be no
      restrictions on the sources of knowledge used by practitioners (the
      postmodernists). We review the postmodernist interventions of Dave Holmes and his
      colleagues, observing that the postmodernist style to which they adhere, which
      includes the use of continental philosophy, metaphors, and acerbic delivery,
      tends to obscure their substantive arguments. The heated nature of some responses
      to them has tended to have the same effect. However, the substantive arguments
      are important. Five main postmodernist charges are identified and discussed. The
      first argument, that the notion of 'best evidence' implies a hierarchical and
      exclusivist approach to knowledge, is persuasive. However, the contention that
      this hierarchy is maintained by the combined pressures of capitalism and vested
      interests within academia and the health services, is less well founded.
      Nevertheless, postmodernist contentions that the hierarchy embraced by the
      evidence-based practice movement damages health care because it excludes other
      forms of evidence that are needed to understand the complexity of care, it
      marginalizes important aspects of clinical knowledge, and it fails to take
      account of individuals or their experience, are all seen to be of some merit.
      However, we do not share the postmodernist conclusion that this adds up to a
      fascist order. Instead, we characterize evidence-based practice as a necessary
      but not sufficient component of health care knowledge.

PMID- 19117569
TI  - Estimating nursing costs--a methodological review.
AB  - A critical cost accounting issue relating to nursing costs is that nursing costs
      are currently averaged into the daily room rate in the hospitals. This accounting
      practice treats nursing units as cost centers as nursing costs are bundled into a
      per diem rate instead of billed separately. As a result, all patients in a given
      care unit of the hospital are presumed to consume the same amount of nursing care
      resources. This costing and billing system creates a mismatch between resources
      consumption and billed charges. The objective of this paper is to (1) demonstrate
      current practice to estimate nursing costs, (2) classify nursing costs into
      direct and indirect costs in order to refine the existing approaches and (3)
      argue that a system of billing nursing costs separately better reflects the costs
      of patient care.

PMID- 19117570
TI  - PPARgamma promoter polymorphisms and acute coronary syndrome.
AB  - BACKGROUND: PPARgamma (PPARg) is a nuclear transcription factor involved in the
      control of lipid and glucose homeostasis. Two PPARg common polymorphisms,
      Pro12Ala and 161C>T, have been found to be associated with cardiovascular
      disease. In this study, in addition to PPARg coding region, we looked for genetic
      variations in promoters and their association with acute coronary syndrome (ACS).
      METHODS: We studied 202 Italian patients with ACS, and 295 healthy Italian
      subjects by dHPLC (denaturing high-performance liquid chromatography),
      heteroduplex analysis and direct sequencing or RFLP (restriction fragment length
      polymorphism) analysis for screening mutations. RESULTS: We identified 7 new and
      2 already published polymorphisms in PPARg promoters. The C>T93695 (promoter 4)
      mutation showed significantly different genotype distribution and allele
      frequency between controls and ACS patients (p<0.001); the T allele conferred a
      protection against ACS at both univariate (OR: 0.45, 95% CI 0.29-0.69: p<0.001)
      and multivariate analysis adjusted for sex, age and traditional cardiovascular
      risk factors (OR: 0.44, 95% CI 0.25-0.76: p<0.005). Moreover, the 161C>T
      polymorphism allele frequency (p=0.03) and genotype distribution (p=0.015)
      resulted to be different in ACS group if compared to healthy controls.
      CONCLUSIONS: The protective role of 93695C>T polymorphism in PPARg promoter in
      ACS suggests that PPARg genetic variants may affect the susceptibility to
      atherosclerotic diseases.

PMID- 19117571
TI  - Asymmetrical strain distributions and neutral axis location of cartilage in
      flexure.
AB  - Flexural deformation has been used for the biomechanical characterization of
      native and engineered cartilage and as a mechanical stimulus to induce alteration
      of cartilage shape during in vitro culture. Flexure is also a physiologically
      relevant mode of deformation for various cartilaginous structures such as the
      ears and nose, but a kinematic description of cartilage in flexure is lacking
      even for simple deformations. The hypothesis of this study was that tension
      compression (T-C) nonlinearity of cartilage will result in asymmetrical strain
      distributions during bending, while a material with similar behavior in tension
      and compression, such as alginate, will have a more symmetrical distribution of
      strains. Strips of calf articular cartilage and alginate were tested under
      uniform circular bending, and strains were determined by a micromechanical
      analysis of images acquired by epifluorescence microscopy. This experimental
      analysis was interpreted in the context of a model of small-deflection, pure
      bending of thin, homogeneous beams of a bimodular elastic material. The results
      supported the hypothesis and showed that marked asymmetry existed in cartilage
      flexural strains where the location of the neutral axis was significantly
      different than the midline and closer to the tensile surface. In contrast,
      alginate samples had a centrally located neutral axis. These experimental results
      were supported by the model indicating that the bimodular simplification of
      cartilage properties is a useful first approximation of T-C nonlinearity in these
      tests. The neutral axis location in cartilage samples was not influenced by the
      testing orientation (towards or away from the superficial-most tissue) or
      magnitude of flexure. These findings characterize the kinematics of cartilage at
      equilibrium during simple bending and indicate that T-C nonlinearity is an
      important determinant of the flexural strain distributions in the tested tissue.

PMID- 19117572
TI  - Rolling rhythms in front crawl swimming with six-beat kick.
AB  - The purpose of this study was to establish the rhythm characteristics of skilled
      front crawl swimmers using a six-beat kick. These included the amplitudes of the
      first three Fourier harmonics (H1, H2, H3) and their percent contributions to
      power contained in the angular displacement signals of the shoulders, hips,
      knees, and ankles with respect to the longitudinal axis in line with the swimming
      direction. Three-dimensional video data of seven national/international level
      swimmers were collected during simulated 200m front crawl races in which swimmers
      maintained six-beat kicking patterns. Swimmers differed in all variables but had
      small variability across the four 50m laps. Modest changes occurred during the
      200m, with the exception of shoulder roll, which remained constant and was
      represented almost entirely by a single sinusoid (H1). Changes across laps
      reached significance for swimming speed, stroke rate, hip roll, and H3 wave
      velocity between the knee and ankle. A H3 body wave of moderate and increasing
      velocity travelled caudally from hip to ankle. In the light of existing knowledge
      of aquatic locomotion this was compatible with the goal of generating propulsion
      in an efficient manner.

PMID- 19117573
TI  - Influence of chondroitin sulfate on the biochemical, mechanical and frictional
      properties of cartilage explants in long-term culture.
AB  - A recent study [Basalo et al., 2007. Chondroitin sulfate reduces the friction
      coefficient of articular cartilage. J. Biomech. 40(8), 1847-1854] has shown that
      the friction coefficient of bovine articular cartilage is reduced significantly
      by the supplementation of chondroitin sulfate (CS) at a concentration of
      100mg/ml. This result suggests that intra-articular injection of CS may be used
      as a prophylactic treatment against the progression of osteoarthritis. The
      objective of this study was to test the hypothesis that long-term culture of
      cartilage explants in CS produces no adverse mechanical, biochemical, or
      cytotoxic effects, while reducing the friction coefficient relative to the
      control group. Long-term cultures of live bovine articular cartilage explants
      were performed with incubation in media containing CS of three different
      concentrations (0, 10 and 100mg/ml). Frictional tests (cartilage-on-glass) were
      performed under constant stress (0.5MPa) for 3600s and the time-dependent
      friction coefficient was measured. Samples incubated in a 100mg/ml of CS solution
      exhibited a significantly lower equilibrium friction coefficient than the control
      (0.05+/-0.01 vs. 0.18+/-0.02 on Day 0, 0.04+/-0.01 vs. 0.14+/-0.04 on Day 7 and
      0.04+/-0.01 vs. 0.15+/-0.06 on Day 14). Samples incubated in 10mg/ml of CS did
      not exhibit any significant decrease in the friction coefficient. Cell viability
      and DNA content were maintained in all groups. However, after 28 days of culture,
      the Young's modulus and glycosaminoglycan content of explants incubated in
      100mg/ml of CS decreased to 5% and 40% of their initial levels, respectively.
      Based on this adverse outcome the hypothesis of this study is rejected, dampening
      our enthusiasm for the use of intra-articular CS injections as a prophylactic
      treatment in osteoarthritis.

PMID- 19117574
TI  - Characterization of pore structure of a strong anion-exchange membrane adsorbent
      under different buffer and salt concentration conditions.
AB  - The quantitative characterization of pore structure of Sartobind Q, a strongly
      basic membrane anion exchanger that is formed by cross-linked cellulose support
      and a hydrogel layer on its pore surface, was made combining the results obtained
      by several experimental techniques: liquid impregnation, batch size-exclusion,
      inverse size-exclusion chromatography, and permeability. Mercury intrusion and
      nitrogen sorption porosimetry were carried out for a dry cellulose support
      membrane in order to get additional information for building a model of the
      bimodal pore structure. The model incorporated the distribution of the total pore
      volume between transport and gel-layer pores and the partitioning of solutes of
      different molecular weights was expressed through the cylindrical pore model for
      the transport pores and random plane model for the gel layer. The effect of
      composition of liquid phase on the pore structure was investigated in redistilled
      water, phosphate and Tris-HCl buffers containing up to 1M NaCl. Evident
      differences in the bimodal pore structure were observed here when both the
      specific volume and size of the hydrogel layer pores significantly decreased with
      the ionic strength of liquid phase.

PMID- 19117575
TI  - Editorial on "Integrated fluidic systems on a nanometer scale and the study on
      behavior of liquids in small confinement" by A. Hibara, T. Tsukahara and T.
      Kitamori.

PMID- 19117576
TI  - Purification of human immunoglobulin G via Fc-specific small peptide ligand
      affinity chromatography.
AB  - Chromatographic resins of a family of linear Fc-binding hexamer peptides (HWRGWV,
      HYFKFD, and HFRRHL) exhibited the ability to selectively adsorb and isolate human
      IgG (hIgG) from complete mammalian cell culture medium (cMEM). Among them, the
      HWRGWV resin with a peptide density of 0.08 mequiv./g of resin was able to purify
      hIgG from cMEM with both purity and yield as high as 95%, comparable to Protein A
      and A2P agarose gels. The influences of N-terminal acetylation of the HWRGWV
      resin, ligand density on the resin, initial hIgG concentration, and temperature
      on IgG isolation were also investigated. The results indicate that these small
      peptide ligands, especially HWRGWV, offer a potential alternative to the use of
      Protein A or Protein G for large scale affinity chromatography.

PMID- 19117577
TI  - Sources of sedimentary PAHs in tropical Asian waters: differentiation between
      pyrogenic and petrogenic sources by alkyl homolog abundance.
AB  - We collected surface sediment samples from 174 locations in India, Indonesia,
      Malaysia, Thailand, Vietnam, Cambodia, Laos, and the Philippines and analyzed
      them for polycyclic aromatic hydrocarbons (PAHs) and hopanes. PAHs were widely
      distributed in the sediments, with comparatively higher concentrations in urban
      areas (Sigma PAHs: approximately 1000 to approximately 100,000 ng/g-dry) than in
      rural areas ( approximately 10 to approximately 100g-dry), indicating large
      sources of PAHs in urban areas. To distinguish petrogenic and pyrogenic sources
      of PAHs, we calculated the ratios of alkyl PAHs to parent PAHs:
      methylphenanthrenes to phenanthrene (MP/P), methylpyrenes+methylfluoranthenes to
      pyrene+fluoranthene (MPy/Py), and methylchrysenes+methylbenz[a]anthracenes to
      chrysene+benz[a]anthracene (MC/C). Analysis of source materials (crude oil,
      automobile exhaust, and coal and wood combustion products) gave thresholds of
      MP/P=0.4, MPy/Py=0.5, and MC/C=1.0 for exclusive combustion origin. All the
      combustion product samples had the ratios of alkyl PAHs to parent PAHs below
      these threshold values. Contributions of petrogenic and pyrogenic sources to the
      sedimentary PAHs were uneven among the homologs: the phenanthrene series had a
      greater petrogenic contribution, whereas the chrysene series had a greater
      pyrogenic contribution. All the Indian sediments showed a strong pyrogenic
      signature with MP/P approximately 0.5, MPy/Py approximately 0.1, and MC/C
      approximately 0.2, together with depletion of hopanes indicating intensive inputs
      of combustion products of coal and/or wood, probably due to the heavy dependence
      on these fuels as sources of energy. In contrast, sedimentary PAHs from all other
      tropical Asian cities were abundant in alkylated PAHs with MP/P approximately 1
      4, MPy/Py approximately 0.3-1, and MC/C approximately 0.2-1.0, suggesting a
      ubiquitous input of petrogenic PAHs. Petrogenic contributions to PAH homologs
      varied among the countries: largest in Malaysia whereas inferior in Laos. The
      higher abundance of alkylated PAHs together with constant hopane profiles
      suggests widespread inputs of automobile-derived petrogenic PAHs to Asian waters.

PMID- 19117578
TI  - Radionuclide ((137)Cs and (40)K) concentrations in the muscle of Baikal seal
      (Pusa sibirica) from Lake Baikal.

PMID- 19117579
TI  - Development and evaluation of a spatially-explicit index of Chesapeake Bay
      health.
AB  - In an effort to better portray changing health conditions in Chesapeake Bay and
      support restoration efforts, a Bay Health Index (BHI) was developed to assess the
      ecological effects of nutrient and sediment loading on 15 regions of the estuary.
      Three water quality and three biological measures were combined to formulate the
      BHI. Water quality measures of chlorophyll-a, dissolved oxygen, and Secchi depth
      were averaged to create the Water Quality Index (WQI), and biological measures of
      the phytoplankton and benthic indices of biotic integrity (P-IBI and B-IBI,
      respectively) and the area of submerged aquatic vegetation (SAV) were averaged to
      create the Biotic Index (BI). The WQI and BI were subsequently averaged to give a
      BHI value representing ecological conditions over the growing season (i.e., March
      October). Lower chlorophyll-a concentrations, higher dissolved oxygen
      concentrations, deeper Secchi depths, higher phytoplankton and benthic indices
      relative to ecological health-based thresholds, and more extensive SAV area
      relative to restoration goal areas, characterized the least-impaired regions. The
      WQI, P-IBI and BHI were significantly correlated with (1) regional river flow (r=
      0.64, -0.57 and -0.49, respectively; p<0.01), (2) nitrogen (N), phosphorus (P)
      and sediment loads (all positively correlated with flow), and (3) the sum of
      developed and agricultural land use (highest annual r(2)=0.86, 0.71 and 0.68,
      respectively) in most reporting regions, indicating that the BHI is strongly
      regulated by nutrient and sediment loads from these land uses. The BHI uses
      ecological health-based thresholds that give an accurate representation of the
      health conditions in Chesapeake Bay and was the basis for an annual, publicly
      released environmental report card that debuted in 2007.

PMID- 19117580
TI  - Public health and human rights: there is no question of 'if'.

PMID- 19117581
TI  - Inequalities, social ties and health in France.
AB  - OBJECTIVES: To discuss the evidence of social health inequalities in France and,
      in this context, to examine the association of social ties and socio-economic
      status (SES) with self-reported health (SRH). STUDY DESIGN: A literature search
      and a nationally representative cross-sectional study of 5046 French adults with
      data about SRH, socio-economic status and relationships with family and friends
      etc. METHODS: SRH was analysed by three measures of SES: income, education and
      socioprofessional group. The frequency of five single and four composite measures
      of social ties by SES was calculated. Logistic regression models estimated the
      association between SRH and the social ties variables. RESULTS: Compared with
      other countries in Western Europe, France has large social class health
      inequalities, particularly in relation to premature male mortality. This study
      found that 'less than good' SRH was significantly more likely to be reported by
      people in lower education, lower socioprofessional and lower income groups.
      Social isolation and weak social relationships were associated with low SES. For
      eight of the nine variables, weak social ties were associated with 'less than
      good' SRH even after adjusting for SES. CONCLUSION: Weak social ties are
      associated with poor health. In the context of a country with large health
      inequalities, the effect of social isolation on health is independent of SES.

PMID- 19117582
TI  - A zoospore inhibition technique to evaluate the activity of antifungal compounds
      against Batrachochytrium dendrobatidis and unsuccessful treatment of
      experimentally infected green tree frogs (Litoria caerulea) by fluconazole and
      benzalkonium chloride.
AB  - Effective and safe treatments of chytridiomycosis in amphibians, caused by
      Batrachochytrium dendrobatidis, are needed to help prevent mortality in captive
      programs for threatened species, to reduce the risk of spread, and to better
      manage the disease in threatened populations. We describe a simple method to
      determine minimum inhibitory concentrations (MICs) of antifungal agents that
      involves adding zoospores to various drug concentrations in 96 well plates and
      microscopic observation after four days. We report results from testing 10
      commercially available antifungal compounds: benzalkonium chloride (<0.78
      microg/ml), povidone iodine (312.5 microg/ml), amphotericin B (3.125 microg/ml),
      fluconazole (<1.56 microg/ml), itraconazole (<1.56 microg/ml), enilconazole
      (<1.56 microg/ml), mercurochrome (6.25 microg/ml), sodium chloride (12.5mg/ml),
      methylene blue (<1.56 microg/ml) and Virkon (3.125 microg/ml). For treatment
      trials of juvenile Litoria caerulea, baths of benzalkonium chloride at 1mg/L and
      fluconazole at 25mg/L were used on 18 experimentally infected frogs per
      treatment. Although these treatments resulted in longer survival times (mean
      43.7+/-11.3 days) than in the untreated controls (37.9+/-9.3 days), the mortality
      rate was still 100%. Higher doses of fluconazole are suggested for further animal
      trials.

PMID- 19117583
TI  - Rapid diagnosis of duck plagues virus infection by loop-mediated isothermal
      amplification.
AB  - Duck virus enteritis is a serious disease among farmed and free-living ducks
      (Anatidae) and a constant threat to the commercial duck industry in China. In
      this study, a loop-mediated isothermal amplification (LAMP) assay was developed
      to rapidly detect and diagnose duck plague virus (DPV) in both farmed and wild
      waterfowl, and compared with polymerase chain reaction (PCR) method and real-time
      PCR method in accuracy, sensitivity and specificity. A set of four specific
      primers was successfully designed to recognize six distinct genomic sequences of
      UL6 protein from DPV, including one forward inner primer, one back inner primer
      and two outer primers. The optimum reaction temperature and time were verified to
      be 61.5 degrees C and 60 min, respectively. Comparative experiments showed that
      LAMP assay was a simple, rapid, accurate, sensitive and specific method for
      detecting DPV, and was superior to PCR assay in sensitivity and specificity for
      DNA amplification. In addition, challenge tests indicated the newly developed
      LAMP method was more sensitive for the diagnosis of DPV infection than virus
      isolation and PCR. LAMP assay would be a good alternative method for on-farm
      disease diagnosis.

PMID- 19117584
TI  - Nonparametric spatial analysis to detect high-risk regions for schistosomiasis in
      Guichi, China.
AB  - Schistosomiasis control in China is facing a new challenge due to the rebound of
      epidemics in many areas and the unsustainable effects of the chemotherapy-based
      control strategy. Identifying high-risk regions for schistosomiasis is an
      important first step for an effective and sustainable strategy. Direct
      surveillance of snail habitats to detect high-risk regions is costly and no
      longer a desirable approach, while indirect monitoring of acute schistosomiasis
      may be a satisfactory alternative. To identify high-risk regions for
      schistosomiasis, we jointly used multiplicative and additive models with the
      kernel smoothing technique as the main approach to estimate the relative risk
      (RR) and excess risk (ER) surfaces by analyzing surveillance data for acute
      schistosomiasis. The feasibility of detecting high-risk regions for
      schistosomiasis through nonparametric spatial analysis was explored and confirmed
      in this study, and two significant high-risk regions were identified. The results
      provide useful hints for improving the national surveillance network for acute
      schistosomiasis and possible approaches to utilizing surveillance data more
      efficiently. In addition, the commonly used epidemiological indices, RR and ER,
      are examined and emphasized from the spatial point of view, which will be helpful
      for exploring many other epidemiological indices.

PMID- 19117585
TI  - Two amino acid residues in the matrix protein M1 contribute to the virulence
      difference of H5N1 avian influenza viruses in mice.
AB  - A/duck/Guangxi/53/2002 (DKGX/53) and A/duck/Fujian/01/2002 (DKFJ/01) are H5N1
      avian influenza viruses that are lethal in chickens. In mice, however, DKFJ/01 is
      highly pathogenic, whereas DKGX/53 displays low pathogenicity. In this study, we
      used reverse genetics to demonstrate that two amino acid residues at positions 30
      and 215 of the M1 protein of these two viruses are important determinants for
      pathogenicity in mice. We thus firstly prove the M1 protein contributes to the
      virulence of H5N1 viruses in mice, and the amino acid residues shown to attenuate
      the virulence could be targeted in influenza virus candidates for live vaccine
      development.

PMID- 19117586
TI  - Effect of mucosal fluid from women with bacterial vaginosis on HIV trans
      infection mediated by dendritic cells.
AB  - Women with bacterial vaginosis (BV) have a higher risk of HIV transmission but
      the cause of risk is unknown. Dendritic cells (DC) are implicated in transmission
      of HIV and we previously observed that DC mature when exposed to mucosal fluid
      from women with BV. We hypothesized that maturation of DC by BV mucosal fluid
      would enhance DC-mediated trans-infection of HIV. Monocyte-derived DC (MDDC) were
      treated with mucosal fluid, incubated with HIV(Bal), and HIV trans-infection was
      evaluated. While LPS-treated MDDC increased HIV(Bal)trans-infection, BV fluid
      reduced trans-infection. HIV(Bal) DNA levels in MDDC were not affected by BV
      fluid or LPS but productive infection of MDDC was decreased by LPS and BV fluid.
      Mucosal fluid from women with BV does not increase MDDC-mediated trans-infection
      suggesting that BV does not increase HIV susceptibility by increasing DC-mediated
      trans-infection. However, indirect effects of DC maturation on HIV transmission
      cannot be ruled out.

PMID- 19117587
TI  - Effects of stratification on chloramine decay in distribution system service
      reservoirs.
AB  - Water quality in chloraminated distribution systems is affected by microbial
      activity, particularly due to nitrifiers that accelerate chloramine decay. In
      summer, continuous thermal stratification increases retention time and lowers
      chloramine residual in some parts of a system service reservoir (tank), relative
      to fully mixed conditions. According to temperature and chemical indicators,
      cooling in winter destratifies these reservoirs naturally. Traditional (chemical)
      indicators of nitrification also suggest that destratification occurs with
      respect to microbiological activity. In contrast, the microbial decay factor
      (F(m)) method, which separates microbiological and chemical decay in bulk water,
      identifies strong microbial stratification, even in winter. F(m) can also be used
      to predict the exacerbated loss of chloramine residual in the following summer,
      which enables early intervention by system managers to minimise such loss, and so
      maintain an adequate residual through the distribution system.

PMID- 19117588
TI  - Growing season surface water loading of fecal indicator organisms within a rural
      watershed.
AB  - The loading of microbial contaminants was examined within the Thomas Brook
      watershed, a 784 ha mixed land-use catchment located in the headwaters of the
      Cornwallis River drainage basin (Nova Scotia, Canada). The objectives were to:
      (i) examine spatial and temporal characteristics of fecal bacteria loading during
      the growing season from five subwatersheds, and (ii) develop areal fecal
      indicator organism export coefficients for rural landscapes. Fecal coliform,
      Escherichia coli, total suspended solids (TSS) concentrations and stream flow
      were monitored at five locations in the watershed over six consecutive growing
      seasons (May-Oct, 2001-2006). A nested watershed monitoring approach was used to
      determine bacterial loading from distinct source types (residential vs.
      agricultural) during both baseflow and stormflow periods. Areal bacterial loading
      rates increased in each nested watershed moving downstream through the watershed
      and were highest in the three subcatchments dominated by agricultural activities.
      Upper watershed bacterial loading throughout the growing season from an
      agricultural subcatchment (Growing Season Avg 8.92 x 10(10) CFU ha(-1)) was
      consistently higher than a residential subcatchment (Growing Season Avg 8.43 x
      10(9) CFU ha(-1)). As expected, annual average stormflow bacterial loads were
      higher than baseflow loads, however baseflow loads still comprised between 14 and
      35% of the growing season bacterial loads in the five subwatersheds. Fecal
      bacteria loads were greater during years with higher annual precipitation. A
      positive linear relationship was observed between E. coli and TSS loading during
      the 2005 and 2006 growing seasons when both parameters were monitored, indicating
      that the processes of sediment transport and bacterial transport are linked. It
      is anticipated that computed areal microbial loading coefficients will be useful
      in developing watershed management plans. More intensive sampling during
      stormflow events is recommended for improving these coefficients.

PMID- 19117589
TI  - Mechanism and kinetics of sulfamethoxazole photocatalytic ozonation in water.
AB  - The photocatalytic ozonation of sulfamethoxazole (SMT) has been studied in water
      under different experimental conditions. The effect of gas flow rate, initial
      concentration of ozone, SMT and TiO2 has been investigated to establish the
      importance of mass transfer and chemical reaction. Under the conditions
      investigated the process is chemically controlled. Both, SMT and TOC kinetics
      have been considered. Fast and slow kinetic regime of ozone reactions have been
      observed for SMT and TOC oxidation, respectively. Application of different
      inhibitors allows for the establishment of reaction mechanism involving direct
      ozonation, direct photolysis, hydroxyl radical reactions and photocatalytic
      reactions. Rate constants of the direct reaction between ozone and protonated,
      non-protonated and anionic SMT species have been determined to be 1.71 x 10(5),
      3.24 x 10(5) and 4.18 x 10(5) M(-1) s(-1), respectively. SMT quantum yield at 313
      nm was found to be 0.012 moles per Einstein at pH 5 and 0.003 moles per Einstein
      at pHs 7 and 9. Main contributions to SMT removal were direct ozone reaction,
      positive hole oxidation and hydroxyl radical reactions. For TOC removal, main
      contributions were due to positive hole oxidation and hydroxyl radical reactions.

PMID- 19117590
TI  - Enhanced performance of crumb rubber filtration for ballast water treatment.
AB  - Waste-tire-derived crumb rubber was utilized as filter media to develop an
      efficient filter for ballast water treatment. In this study, the effects of
      coagulation, pressure filtration and dual-media (gravity) filtration on the
      performance of the crumb rubber filtration were investigated. The removal
      efficiencies of turbidity, phytoplankton and zooplankton, and head loss
      development were monitored during the filtration process. The addition of a
      coagulant enhanced the removal efficiencies of all targeted matter, but resulted
      in substantial increase of head loss. Pressure filtration increased filtration
      rates to 220 m(3)h(-1)m(-2) for 8-h operation and improved the zooplankton
      removal. Dual-media (crumb rubber/sand) gravity filtration also improved the
      removal efficiencies of phytoplankton and zooplankton over mono-media gravity
      crumb rubber filtration. However, these filtration techniques alone did not meet
      the criteria for removing indigenous organisms from ballast water. A combination
      of filtration and disinfection is suggested for future studies.

PMID- 19117591
TI  - Pentachlorophenol decomposition by electron beam process enhanced in the presence
      of Fe(III)-EDTA.
AB  - This study focuses on the enhanced decomposition of pentachlorophenol (PCP) in an
      electron beam (E-beam) process. To attain this objective, we investigated a
      synergistic effect of ferric-ethylenediamineacetate (Fe(III)-EDTA) and H(2)O(2)
      as additives to produce additional hydroxyl radical (*OH) at low dose. In this
      process, aqueous electron and hydrogen atom rapidly react with O(2) molecules,
      thereby forming hydroperoxyl/superoxide anion radical (HO2*/O(2)(-)), which
      reduces the Fe(III)-EDTA into Fe(II)-EDTA. Further *OH is produced by a well
      known Fenton-like reaction of Fe(II)-EDTA with H(2)O(2) formed newly in E-beam.
      The complete decomposition of the initial PCP at 0.1mM was enhanced even at very
      low dose (<10 kGy) with 20 microM Fe(III)-EDTA and H(2)O(2) less than 1mM. This
      observation was supported by the increased amount of Cl(-) produced by the
      decomposition of PCP. Thus, in the presence of Fe(III)-EDTA during E-beam
      irradiation, the HO2*/O(2)(-)-driven Fenton-like reaction produces much more
      ()OH, which is significant for the complete degradation of PCP.

PMID- 19117592
TI  - Octanol-air partition coefficients of polybrominated biphenyls.
AB  - The octanol-air partition coefficients (K(OA)) for PBB15, PBB26, PBB31, PBB49,
      PBB103 and PBB153 were determined as a function of temperature using a gas
      chromatographic retention time technique with 1,1,1-trichloro-2,2-bis (4
      chlorophenyl) ethane (p,p'-DDT) as a reference substance. The internal energies
      of phase change from octanol to air (Delta(OA)U) were calculated for the six
      compounds and were in the range from 74 to 116 kJ mol(-1). Simple regression
      equations of log K(OA) versus relative retention times (RRTs) on gas
      chromatography (GC), and log K(OA) versus molecular connectivity indexes (MCI)
      were obtained, for which the correlation coefficients (r(2)) were greater than
      0.985 at 283.15K and 298.15K. Thus the K(OA) values of the remaining PBBs can be
      predicted by using their RRTs and MCI according to these relationships.

PMID- 19117593
TI  - Trace element deposition and trends during a ten year period in Finland.
AB  - The deposition of aluminium, arsenic, cadmium, chromium, copper, iron, lead,
      manganese, nickel, vanadium and zinc in bulk precipitation was examined at eight
      background stations in Finland during the last 10 years (1998-2007). The annual
      deposition was from the lowest values to the highest Cd<As<Cr<Ni<V<Cu and
      Pb<Mn<Zn<Al<Fe. Most of the elements had a south to north decreasing gradient
      mainly due to minor domestic emissions in the north, growing distance to the
      large European source areas and differences in the length of snow-cover period.
      Element enrichment factors divided the trace elements to the following
      categories: (1) slightly enriched Cr, Fe and Mn; (2) moderately enriched Cu, Ni
      and V; and (3) highly enriched As, Cd, Pb and Zn. Trend analysis of annual
      depositions showed that the established decreasing trend in As and Pb deposition
      continued during our study period while Cr, Cu and Fe depositions have lately
      increased. No statistically significant trends were detected for Cd, Mn, Ni, V
      and Zn during the studied years. Additionally, the measurement uncertainty of
      trace elements was evaluated for the whole measurement chain.

PMID- 19117594
TI  - Antimony sinks in the weathering crust of bullets from Swiss shooting ranges.
AB  - Shooting ranges represent sites heavily polluted by Pb, Sb, Cu, Ni, and Zn, which
      are released during the weathering of bullets. The pristine bullets are made of a
      Pb-Sb core, Fe mantle, and minor amounts of Cu, Ni, and Zn in an interlayer
      between the core and mantle. At two selected sampling sites (Losone and Lucerne,
      both in Switzerland), corroding bullets were collected to determine the sinks of
      Sb within the weathering crust of the bullets. Bulk Sb concentrations in the
      crust were found to be as high as 1.3 wt.%. The oxalate-extractable fraction of
      Fe showed that the amorphous Fe oxides (e.g., ferrihydrite) prevail over goethite
      and lepidocrocite, which were identified by bulk X-ray diffraction experiments.
      Crystalline Pb phases are litharge (only found by X-ray diffraction) and
      cerussite, which result from weathering of the Pb core. No distinct Sb minerals
      were identified by X-ray diffraction. Investigations with electron microprobe
      (EMP) showed that Sb is mostly accumulated in those regions in the weathering
      crust where there is also a high concentration of Fe. In the weathering crust
      from Losone, such Fe-rich regions with Sb are represented by material that
      cements or rims silicate mineral grains. The cement was identified as
      lepidocrocite by micro-Raman analysis. At Lucerne, Sb is found in Fe-oxide
      aggregates, in sawdust particles where it may be bound to organic matter, or in
      aggregates enriched in Pb and depleted in Fe. Bulk EXAFS experiments suggested
      that the Fe oxides are the most important sink for Sb. Our modelling of Sb next
      nearest neighbours suggests two types of inner-sphere complexes on the surfaces
      of Fe oxides. These are edge- and corner-sharing adsorption complexes. Hence, the
      predominant sink of Sb in the weathering crust of the bullets at the selected
      shooting ranges is Fe oxides, amorphous or crystalline.

PMID- 19117595
TI  - The risk of infections with biologic therapies for rheumatoid arthritis.
AB  - OBJECTIVES: To assess the risk of serious and nonserious bacterial and viral
      infections associated with the use of biologic therapy (abatacept, adalimumab,
      anakinra, etanercept, infliximab, and rituximab) in patients with rheumatoid
      arthritis (RA). METHODS: Information was derived from PubMed, EMBASE, and the
      Cochrane clinical trials register and database of systematic reviews and relevant
      congress abstracts up to and including February 2008. RESULTS: Compared with the
      general population, patients with RA have a heightened risk of infection,
      including tuberculosis. Long-term clinical trials and postmarketing studies
      indicate that anakinra and the tumor necrosis factor (TNF) inhibitors are
      associated with an increased risk of infections versus conventional disease
      modifying antirheumatic drugs (DMARDs), especially early in the course of
      treatment. The most common sites of infection are the respiratory tract
      (including pneumonia), skin and soft tissue, and the urinary tract. The risk of
      tuberculosis also appears higher with TNF inhibitors (in particular, infliximab)
      versus DMARDs, although this can be reduced by screening and prophylaxis. TNF
      inhibitors do not appear to significantly increase the risk of reactivating
      chronic viral infections. Influenza and pneumococcal vaccinations are generally
      effective in the face of TNF inhibitors or abatacept. Available data suggest that
      the risk of infections and serious infections with abatacept and rituximab may be
      similar to that of the TNF inhibitors. To date, there have been no reports from
      clinical trials of increased tuberculosis or opportunistic infections with
      abatacept or rituximab. CONCLUSIONS: All marketed TNF inhibitors for compared to
      control RA appear to increase the risk of serious and nonserious infections
      compared with DMARDs. Although suggestive, data for abatacept and rituximab are
      less definitive and longer periods of patient exposure to these agents are needed
      before an assessment of their risks can be made.

PMID- 19117597
TI  - JAK2V617F mutation screening in patients with retinal vein thrombosis or
      recurrent fetal loss.

PMID- 19117596
TI  - First report on the effect of thrombin and factor Xa on cardiomyocytes in a three
      dimensional cell culture model.

PMID- 19117598
TI  - Intraoperative gross assessment of myometrial invasion and cervical involvement
      in endometrial cancer: Role of tumor grade and size.
AB  - OBJECTIVES: To evaluate the accuracy of visual examination of myometrial invasion
      and the involvement of the cervix in the hysterectomy specimen and to explore the
      role of tumor grade and size in the accuracy of gross estimation of myometrial
      invasion. METHODS: In 142 patients with apparent early endometrial cancer the
      uterus was opened after its removal and inspected. The size of the tumor (<or= or
      >2 cm), the depth of myometrial invasion (less or greater than 50%) and the
      involvement of the cervix (as positive or negative) were visually estimated and
      recorded. All patients underwent surgical staging. The gross findings were
      compared with the final histological results. Estimations of myometrial
      invasiveness were analyzed according to the tumor grade and size. Accuracy,
      specificity, sensitivity, positive and negative predictive values were
      calculated. RESULTS: The overall accuracy rate for myometrial invasion was 81.7%
      (116/142). False positive and false negative results noted in 17/101 (17%) and
      9/41 (21.9%) of patients. Sensitivity, specificity, positive and negative
      predictive values were 78%, 83.2%, 65.3% and 90.3% respectively. Gross estimation
      of invasion was more often successful in patients with smaller (<or=2 cm) than in
      those with grater tumors (accuracy 88.9% vs. 79.2%). Increasing tumor grade found
      to diminish the rate of correct prediction. The accuracy for grade I tumors was
      93.5%, for grade II 80.4% and only 58.6% for grade III lesions. Cervical
      involvement was correctly evaluated in 138/142 patients with one false positive
      and 3 false negative results. CONCLUSION: These data show that gross estimation
      of myometrial invasion is highly accurate in small (<or=2 cm) and grade I tumors.
      Visual evaluation of cervical involvement is also reliable. However, prediction
      of myometrial invasion is lower in tumors with higher grade, being poor in grade
      III lesions. Inaccuracies of preoperative histology may decrease the sensitivity
      of intraoperative assessment based on final grade.

PMID- 19117599
TI  - Anaphylaxis fatalities and admissions in Australia.
AB  - BACKGROUND: Detailed data on fatal anaphylaxis are limited, with national
      anaphylaxis fatality data for the United Kingdom and food-induced anaphylaxis
      fatality data for the United States. Time trends for anaphylaxis fatalities are
      not available. OBJECTIVE: We examined causes, demographics, and time trends for
      anaphylaxis fatalities in Australia between January 1997 and December 2005 and
      compared these with findings for anaphylaxis admissions. METHODS: Data on
      anaphylaxis deaths and hospital admissions were extracted from a national
      database. Death certificate codes were analyzed to determine the likely cause and
      associated comorbidities. RESULTS: There were 112 anaphylaxis fatalities in
      Australia over 9 years. Causes were as follows: food, 7 (6%); drugs, 22 (20%);
      probable drugs, 42 (38%); insect stings, 20 (18%); undetermined, 15 (13%); and
      other, 6 (5%). All food-induced anaphylaxis fatalities occurred between 8 and 35
      years of age with female preponderance, despite the majority of food-induced
      anaphylaxis admissions occurring in children less than 5 years of age. Most
      insect sting-induced anaphylaxis deaths occurred between 35 and 84 years almost
      exclusively in male subjects, although bee sting-induced admissions peak between
      5 and 9 years of age with a male/female ratio of 2.7. However, most drug-induced
      anaphylaxis deaths occurred between 55 and 85 years with equal sex distribution
      similar to drug-induced anaphylaxis admissions. There was no evidence of an
      increase in death rates for food-induced anaphylaxis, despite food-induced
      anaphylaxis admissions increasing approximately 350%. In contrast, drug-induced
      anaphylaxis deaths increased approximately 300% compared with an approximately
      150% increase in drug-induced anaphylaxis admissions. CONCLUSION: The
      demographics for anaphylaxis deaths are different to those for anaphylaxis
      presentations. Anaphylaxis mortality rates remain low and stable, despite
      increasing anaphylaxis prevalence, with the exception of drug-induced anaphylaxis
      deaths, which have increased.

PMID- 19117601
TI  - Evaluation of oxidative DNA damage promoted by storage in sperm from sex-reversed
      rainbow trout.
AB  - Short-term storage and cryopreservation of sperm are two common procedures in
      aquaculture, used for routine practices in artificial insemination reproduction
      and gene banking, respectively. Nevertheless, both procedures cause injuries
      affecting sperm motility, viability, cell structure and DNA stability, which
      diminish reproductive success. DNA modification is considered extremely
      important, especially when sperm storage is carried out with gene banking
      purposes. DNA damage caused by sperm storage is not well characterized and
      previous studies have reported simple and double strand breaks that have been
      attributed to oxidative events promoted by the generation of free radicals during
      storage. The objective of this study was to reveal DNA fragmentation and to
      explore the presence of oxidized bases that could be produced by oxidative events
      during short-term storage and cryopreservation in sex-reversed rainbow trout
      (Oncorhynchus mykiss) spermatozoa. Sperm from six males was analyzed separately.
      Different aliquots of the samples were stored 2h (fresh) or 5 days at 4 degrees C
      or were cryopreserved. Then spermatozoa were analyzed using the Comet assay, as
      well as combining this method with digestion with two endonucleases from
      Escherichia coli (Endonuclease III, that cut in oxidized cytosines, and FPG,
      cutting in oxidized guanosines). Both storage procedures yielded DNA
      fragmentation, but only short-term storage oxidative events were clearly
      detected, showing that oxidative processes affect guanosines rather than
      cytosines. Cryopreservation increases DNA fragmentation but the presence of
      oxidized bases was not noticed, suggesting that mechanisms other than oxidative
      stress could be involved in DNA fragmentation promoted by freezing.

PMID- 19117600
TI  - Administration of sulpiride or domperidone for advancing the first ovulation in
      deep anestrous mares.
AB  - Since results with using sulpiride and domperidone are conflicting and since both
      have not been tested at the same time, the aim of this study was to compare the
      efficacy of these substances for the induction of ovulation in deep anestrous
      mares in the same experimental conditions and to determine their fertility after
      artificial insemination (AI) at the induced estrus. Twenty-six non-pregnant, non
      lactating standardbred anestrous mares were randomly assigned to three groups and
      treated daily for 25 days (from February 3rd to February 28th) with either
      sulpiride (1mg/kg of body weight im SID, n=10), or domperidone (1mg/kg po SID,
      n=10); 6 animals were used as control. The beginning of the transition period and
      the first ovulation were hastened in sulpiride (16.4+/-0.8 days) but not in
      domperidone (46.0+/-3.3 days) treated mares (P<0.05). The diameter of the largest
      follicle was affected by treatment, time and interaction of treatment-by-day
      (P<0.05) and significantly increased in the sulpiride group (P<0.05). Although a
      main effect of treatment on plasma LH concentration was not observed (P=0.06),
      time and interaction of treatment-by-day were statistically significant (P<0.05).
      The interval from the beginning of treatment to first ovulation was shorter
      (P<0.05) in the sulpiride group (36.9+/-2.5 days) than in the domperidone (74.7+/
      3.3 days) and control (81.4+/-3.1) groups. The establishment of pregnancy was
      significantly (P<0.05) hastened in sulpiride (61.0+/-35.2 days) but not in
      domperidone (83.0+/-44.0 days) treated mares. Treated mares not pregnant after
      the first AI, showed normal estrous cycles with regular interovulatory intervals
      (P>0.05). It was concluded that sulpiride is effective in advancing the beginning
      of transition period and the first ovulation whereas domperidone is successful
      only in some mares.

PMID- 19117602
TI  - Higher non-return rate associated with Mycobacterium avium subspecies
      paratuberculosis infection at early stage in Holstein dairy cows.
AB  - The effects of infection by Mycobacterium avium paratuberculosis (Map) on dairy
      cows are poorly documented and quite controversial. This retrospective study
      aimed at quantifying the variation in non-return to service of Holstein dairy
      cows according to their Map-infection status. Three different statuses were
      defined based on both individual and herd tests results: ELISA positive cow, all
      tests negative cow in a negative herd and all tests negative cow in a positive
      herd. Whatever the age at Map testing, the status was attributed to a cow from
      its first lactation onwards. Non-return to service was determined at 200 days
      after first and second services. The study was performed from 1999 to 2007 on
      185,950 AI from 48,914 cows in early stage of the infection in 1069 herds by
      logistic regression controlling for known factors influencing non-return rate.
      Non-return rate was higher for infected cows compared to negative cows from
      negative herds (RR of 1.10 or +3.9 points of % of non-return rate). The effect
      was significant for parities 1 and 2 (RR of 1.11 and 1.12, respectively) but not
      for higher ones. This effect was lower when comparing positive cows to negative
      cows in the same herds but relative risks were still above 1. The hypothesis that
      the effect of Map on non-return depends upon the stage of infection is
      formulated.

PMID- 19117603
TI  - Ultrastructural characterization of fresh and cryopreserved in vivo produced
      ovine embryos.
AB  - Controlled slow freezing and vitrification have been successfully used for ovine
      embryo cryopreservation. Selection of embryos for transfer is based on
      stereomicroscopical embryo scoring after thawing, but the subjectivity inherent
      to this selection step has been demonstrated by ultrastructural studies of
      controlled slow frozen, in vivo produced ovine morulae and blastocysts. These
      studies have shown that certain abnormalities remain undetected by
      stereomicroscopy only. In the present study, using ovine in vivo produced morulae
      and blastocysts, we have studied the ultrastructural alterations induced by open
      pulled straw vitrification (OPS) and controlled slow freezing, compared
      stereomicroscopical embryo scoring with light microscopy evaluation of embryo's
      semithin sections, and related the ultrastructural cellular damage with the
      embryo classification by stereomicroscopical embryo scoring of embryos' and
      semithin section evaluation by light microscopy. The ultrastructural lesions
      found for OPS-vitrified and controlled slow frozen embryos were similar,
      independently of embryo stage. A significant higher number of grade 3 embryos was
      found at stereomicroscopical scoring after controlled slow freezing (P=0.02), and
      a significant higher number of grade 3 blastocysts was found at semithin
      sectioning after OPS vitrification (P=0.037). The extension of ultrastructural
      damage, especially of mitochondria and cytoskeleton, was related to the semithin
      classification but not to stereomicroscopical scoring at thawing. This suggests
      that semithin scoring is a useful tool for predicting ultrastructural lesions and
      new improvements in cryopreservation and thawing methods of ovine embryos are
      still warranted, including in the case of blastocysts cryopreserved by OPS
      vitrification.

PMID- 19117604
TI  - Effect of semen dilution to low-sperm number per dose on motility and
      functionality of cryopreserved bovine spermatozoa using low-density lipoproteins
      (LDL) extender: comparison to Triladyl and Bioxcell.
AB  - Artificial insemination with doses containing low-sperm numbers has been utilized
      to optimize the use of elite bulls. Hen egg yolk is widely used as a
      cryoprotective agent in semen freezing extender protecting the spermatozoa. Its
      action is due to the presence of low-density lipoproteins (LDL) in the hen egg
      yolk. The objectives of the present study were to evaluate the effects of the
      semen dilution to low-sperm number/dose on sperm motility and integrity of sperm
      plasma membrane in the cryopreservation process, using two commercial extenders
      (Triladyl, Bioxcell and LDL extender prepared in our laboratory, 97% purity.
      Fifteen ejaculates were collected from five fertile crossbred bulls (Bos
      taurusxBos indicus). After collection, sperm motility was examined by Computer
      Assisted Semen Analysis (Hamilton Thorne), morphological sperm characteristics
      were evaluated by differential interference microscopy and the integrity of
      plasma membranes was determined using the hypo-osmotic swelling test. The semen
      was subsequently divided into three aliquots and diluted with the three extenders
      into 120 x 10(6), 60 x 10(6) and 20 x 10(6)sperm/mL, corresponding to 30 x 10(6),
      15 x 10(6) and 5 x10(6) sperm/dose, respectively. This study revealed that LDL
      extender was more effective in preservation of motility and integrity of the
      plasma membrane of spermatozoa than Bioxcell and Triladyl (p<0.05), but no
      significant difference was observed between Triladyland Bioxcell. Therefore we
      can conclude that LDL extender could be used instead of Triladyl or Bioxcellat
      low semen concentration per dose for elite bulls, it also could be envisaged for
      the industry of sex-stored semen.

PMID- 19117605
TI  - Semantic domain-specific functional integration for action-related vs. abstract
      concepts.
AB  - A central topic in cognitive neuroscience concerns the representation of concepts
      and the specific neural mechanisms that mediate conceptual knowledge. Recently
      proposed modal theories assert that concepts are grounded on the integration of
      multimodal, distributed representations. The aim of the present work is to
      complement the available neuropsychological and neuroimaging evidence suggesting
      partially segregated anatomo-functional correlates for concrete vs. abstract
      concepts, by directly testing the semantic domain-specific patterns of functional
      integration between language and modal semantic brain regions. We report evidence
      from a functional magnetic resonance imaging study, in which healthy participants
      listened to sentences with either an action-related (actions involving physical
      entities) or an abstract (no physical entities involved) content. We measured
      functional integration using dynamic causal modeling, and found that the left
      superior temporal gyrus was more strongly connected: (1) for action-related vs.
      abstract sentences, with the left-hemispheric action representation system,
      including sensorimotor areas; (2) for abstract vs. action-related sentences, with
      left infero-ventral frontal, temporal, and retrosplenial cingulate areas. A
      selective directionality effect was observed, with causal modulatory effects
      exerted by perisylvian language regions on peripheral modal areas, and not vice
      versa. The observed condition-specific modulatory effects are consistent with
      embodied and situated language processing theories, and indicate that linguistic
      areas promote a semantic content-specific reactivation of modal simulations by
      top-down mechanisms.

PMID- 19117606
TI  - Endogenous inhibitors of angiogenesis: a historical review.
AB  - Under physiological conditions, angiogenesis is regulated by the local balance
      between endogenous stimulators and inhibitors of this process. In pathological
      states such as chronic inflammation and tumor growth, there is an imbalance
      between endogenous stimulator and inhibitor levels, leading to an "angiogenic
      switch". Various inhibitors of angiogenesis, including angiostatin, endostatin
      and thrombospondins, are found in the body. It is uncertain why the body
      possesses so many inhibitors, and also how these inhibitors interact to overcome
      the effects of angiogenesis stimulators. This review summarizes the present
      knowledge about endogenous inhibitors of angiogenesis.

PMID- 19117607
TI  - Acute-phase protein response in pigs experimentally infected with Haemophilus
      parasuis.
AB  - The acute-phase protein (APP) response to an infection caused by Haemophilus
      parasuis, the etiological agent of Glasser's disease in pigs, was characterized
      measuring serum concentrations of pig major acute-phase protein (pig MAP),
      haptoglobin (HPT), C-reactive protein (CRP) and apolipoprotein A-I (ApoA-I) in
      colostrum-deprived pigs. They were divided into six experimental groups: non
      immunized control group (I); immunized with a non-commercial bacterin (II); with
      an OMP-vaccine (III); with a sublethal dose (IV); and with two commercial
      bacterins (V and VI). All groups were challenged intratracheally with 5 *
      10(9)CFU of H. parasuis 37 days after immunisation. The highest levels of the
      positive APPs (pig MAP, HPT and CRP) and the lowest levels of the negative APPs
      (ApoA-I) were observed in the animals that died as a consequence of the
      infection, both those in the non-immunized and in the immunized groups. However,
      the surviving animals (all of them in groups II, V and VI, two pigs in group III,
      and three in group IV) showed a minor variation in APP response, mainly on day 1
      post-challenge (p.c.), and then tended to recover the initial values. APP
      response was still less pronounced in the groups of pigs previously immunized
      with bacterins. In conclusion, APP response can reflect Glasser-disease ongoing,
      showing a correlation between the severity and duration of the clinical signs and
      lesions and the magnitude of changes in the APP levels.

PMID- 19117608
TI  - Biological effects of a complex of vanadium(V) with salicylaldehyde semicarbazone
      in osteoblasts in culture: mechanism of action.
AB  - Vanadium compounds display important pharmacological actions in vivo and in vitro
      systems. Semicarbazones are versatile ligands with therapeutic effects. Herein,
      we report the effects of V(V)O(2)(salicylaldehydesemicarbazone) (V(V)-Salsem) on
      two osteoblast cell lines in culture (MC3T3-E1 and UMR106). V(V)-Salsem inhibited
      cell proliferation in a dose response manner. At 100muM, the complex caused an
      inhibition of ca. 48% and 38% for the normal and the tumoral osteoblasts,
      respectively (p<0.001). This inhibition could be partially reversed to 35% and
      28% by NAC (N-acetylcysteine) and a mixture of vitamins E and C. Changes in cell
      proliferation correlated with morphological alterations and the disruption of
      actin cytoskeleton fibers. The complex also enhanced the level of ROS (reactive
      oxygen species) up to ca. 100% over basal in both cell lines. Activation of ERK
      signalling cascade was also observed. These events led to apoptosis (up to 44% in
      MC3T3-E1 and 33% in UMR106 cells). Scavengers of ROS and inhibitors of ERK
      cascade allowed to elucidate the mechanisms involved in the cytotoxicity. In
      conclusion, V(V)-Salsem displayed cytotoxic effects on osteoblasts in culture
      through the production of free radicals and the activation of ERK cascade. These
      mechanisms triggered the apoptotic events that conveyed to cell death.

PMID- 19117609
TI  - Diagnosis and prevalence of enteropathogenic bacteria in children less than 5
      years of age with acute diarrhea in Tehran children's hospitals.
AB  - INTRODUCTION: Acute diarrhea disease is the second cause of death among all
      infectious diseases in children younger than 5 years of age worldwide. The aim of
      this study was to employ a combination of biochemical, microbiological and
      molecular diagnostic techniques to investigate the stools of Iranian children
      with acute diarrhea for bacterial enteropathogens. METHOD: Diarrheagenic
      Escherichia coli, Shigella spp., Salmonella spp., Campylobacter spp. and Yersinia
      spp., were investigated from June 2003 to June 2005, in 1087 children less than 5
      years old with acute diarrhea. Stool specimens from children were studied for
      enteropathogens both by standard culturing and molecular methods. This study was
      designed on hospital based. RESULT: The highest incidence values were found in
      the summer and in children less than 1-year-old (42.7%). The Pathogenic bacteria
      recovered out from fecal samples of 555 (55.1%) patients had the following
      profile: Shigella spp. (26.7%) was the most prevalent bacterial pathogen and
      Shiga-like toxin producing E. coli (STEC) and Enteroaggregative E. coli (EAEC)
      105 (18.9%) and 92 (16.6%) had the second and third highest prevalence,
      respectively. Enteropathogenic E. coli (EPEC), Campylobacter, Salmonella and
      Enterotoxigenic E. coli (ETEC) were found in 70 (12.6%), 60 (10.8%), 42 (7.6%),
      and 38 (6.8%) positive samples, respectively. In this study neither Yersinia nor
      E. coli O157:H7 were found. Of the 30 co-infections detected, Shigella flexneri
      and Campylobacter jejuni accounted for more than 50%. CONCLUSION: Information
      about the prevalence of wide-range Shigella and STEC may facilitate the control
      and management of infant diarrhea diseases in Iran. The results of this study
      suggest that comprehensive surveys are needed in different parts of the country
      in order to identify the incidence of different enteropathogenic diarrhea,
      especially diarrheagenic E. coli in children in Iran.

PMID- 19117610
TI  - Cognitive functioning of bipolar I patients and relatives from families with or
      without schizophrenia or schizoaffective disorder.
AB  - BACKGROUND: Bipolar I disorder patients show cognitive impairments, and genetic
      vulnerability to other psychotic disorders may modify these impairments. We set
      out to assess cognitive functions and estimate their heritability in bipolar I
      disorder patients (bipolar families) and unaffected relatives in a group of
      families with bipolar I disorder only and in another group of families with both
      bipolar I disorder and schizophrenia or schizoaffective disorder (mixed
      families). METHODS: A neuropsychological test battery was administered to 20
      bipolar patients and 36 relatives from bipolar families, 19 bipolar patients and
      28 relatives from mixed families and 55 controls, all representing population
      based samples. RESULTS: Irrespective of the family group, patients and relatives
      were impaired in psychomotor processing speed. Both patient groups were impaired
      in executive functioning, but the deficit was more severe in patients from mixed
      families. Patients from bipolar families scored lower than controls in nearly all
      measures of verbal memory. All relatives were slightly impaired in executive
      functioning. The heritability of cognitive functions was generally similar
      irrespective of psychopathology in the family. However, there were greater
      genetic effects in several cognitive tasks in mixed families. LIMITATIONS: The
      small sample size and familial type of bipolar disorder could limit the
      generalizability of the results. CONCLUSION: Impaired psychomotor processing
      speed and executive functions may represent markers of susceptibility to bipolar
      I disorder irrespective of psychopathology within the family. Generalized
      impairment in verbal memory, in turn, may associate more with bipolar disorder
      than to vulnerability to other psychotic disorders.

PMID- 19117612
TI  - Expressed gene sequence of bovine IL23A and IL23R.
AB  - The cloning and characterization of bovine IL23A and IL23 receptor cDNA from
      total RNA of PBMC and the genomic organization of the coding sequences are
      reported. The IL23A partial coding region was found to be 578 nucleotides coded
      for in 4 exons and shared 84% and 76% identity with human and mouse sequences,
      respectively. The IL23R complete coding region had 1890 nucleotides coded for in
      10 exons and shared 87% and 73% homology with the human and mouse sequences,
      respectively. Both bovine sequences were more closely related to the human
      sequences than were mouse sequence. This work was done as part of the U.S.
      Veterinary Immune Reagent Network whose goal is to develop reagents for
      investigating diseases in livestock species, poultry and fish.

PMID- 19117611
TI  - Molecular cloning, in vitro expression and bioactivity of dog A proliferation
      inducing ligand (APRIL).
AB  - A proliferation-inducing ligand (APRIL) is a novel member of the tumor necrosis
      factor (TNF) family, which is involved in immune regulation. In this study, the
      cDNA of dog APRIL (dAPRIL) was amplified from dog spleen by RT-PCR. The open
      reading frame (ORF) of dAPRIL encodes a protein of 250-amino acid, containing a
      predicted transmembrane domain and a putative furin protease cleavage site like
      other mammalian APRILs. The amino acid identities between biologically soluble
      dAPRIL and its pig, human, rabbit and mouse counterparts are 91%, 86%, 88% and
      86%, respectively, dramatically higher than most other known cytokines. The
      result of real-time PCR revealed that dAPRIL is expressed in various tissues and
      is elevated in thymus and spleen. Recombinant soluble dAPRIL (dsAPRIL) fused with
      NusA.tag was efficiently produced in Origami B (DE3) pLysS expression host
      strain. In vitro, purified dsAPRIL was able to co-stimulate the proliferation of
      dog splenic B cells in response to anti-IgM. These findings indicate that dAPRIL
      plays an important role in survival/proliferation of dog B cells and provide the
      basis for investigation on the roles of APRIL in this important domestic species.

PMID- 19117613
TI  - Molecular cloning, expression, and bioactivity of dove B lymphocyte stimulator
      (doBAFF).
AB  - B cell activating factor (BAFF) belonging to the tumor necrosis factor (TNF)
      family is a novel member of the tumor necrosis factor ligand family and plays an
      important role in B lymphocyte maturation and survival. cDNA of dove B lymphocyte
      stimulator (doBAFF) was amplified from total RNA of dove spleen by RT-PCR
      (reverse transcription PCR). The open reading frame of doBAFF consists 867 bases
      encoding a protein of 288 amino acids. Sequence comparison indicated the amino
      acid sequence of doBAFF showed high identity to hBAFF (50.66%) and cBAFF
      (91.32%). The result of RT-PCR showed that doBAFF was highly expressed in the
      spleen and bursa of fabricius. To enhance the soluble expression of doBAFF in
      Escherichia coli, we fused the extracellular region of doBAFF gene with a small
      ubiquitin-related modifier gene (SUMO) by over-lap PCR. The resulting fused
      protein SUMO-sdoBAFF was highly expressed in DE3(BL21) with a molecular weight of
      35kDa. The fusion protein was purified by Ni-NTA affinity chromatography and
      cleaved by a SUMO-specific protease, Ulp1. The sdoBAFF protein was further
      purified by Ni-NTA affinity chromatography. In vitro, the MTT assays indicated
      that the purified doBAFF as well as SUMO-sdoBAFF proteins were able to promote
      bursa lymphocyte survival in dose-dependent manner.

PMID- 19117614
TI  - Neonatal bacterial endotoxin challenge interacts with stress in the adult male
      rat to modify KLH specific antibody production but not KLH stimulated ex vivo
      cytokine release.
AB  - While postnatal bacterial infection is capable of inducing a variety of long
      lasting functional alterations in immune function, the specific physiological
      pathways responsible for this modification are largely unknown. In the current
      investigation we explore the hypothesis that early life exposure to endotoxin
      permanently modifies the function of T helper (Th) cell activity. Therefore we
      examined Th-cell regulated in vivo humoral and ex vivo cellular responses to
      keyhole limpet hemocyanin (KLH). Given that stress has been shown to exacerbate
      some of the immunological alterations exhibited by the neonatally endotoxin
      challenged adult, we examined the adult's Th1/Th2 responses to KLH under
      conditions of no stress, acute stress (2 daysx2 h), and chronic stress (7 daysx2
      h). Our results demonstrate that adults neonatally challenged with endotoxin were
      found to produce significantly less IgG1 following KLH challenge following acute
      stress (p<0.05). Neonatally endotoxin treated animals exposed to acute stress
      were also found to produce less IgM than saline or endotoxin treated animals
      exposed to no-stress or chronic stress. No neonatal treatment group differences
      observed in the production of INF-gamma or IL-4 in adulthood. In summary, the
      results from the present study provide little evidence to directly support the
      hypothesis that neonatal endotoxin exposure significantly alters the Th1/Th2
      balance in adulthood.

PMID- 19117616
TI  - Ectopic cervical thymus: is empiric surgical excision necessary?
AB  - Ectopic cervical thymus (ECT) is an uncommon cause of pediatric neck masses. We
      present the first algorithm for conservative management of this benign disease.
      The natural history of ECT is unclear since most cases in the literature have
      undergone surgical excision. This is due to concern for malignant transformation,
      however, no convincing evidence was found in the literature to support this. With
      accurate diagnosis, clinically asymptomatic patients can be conservatively
      managed, as the thymus is expected to involute naturally.

PMID- 19117615
TI  - The effect of increased inner ear pressure on tympanic membrane vibration.
AB  - BACKGROUND & OBJECTIVE: It has been suggested that increased inner ear pressure
      can affect the stiffness of the tympano-ossicular conductive system. However, the
      published literature contains few studies on changes of middle ear mechanics
      caused by increased inner ear pressure. In this study, we evaluated the effects
      of increased inner ear pressure on tympanic membrane vibration in guinea pigs
      using a laser Doppler vibrometer (LDV). MATERIALS AND METHODS: We used 10 male
      guinea pigs (weighing 250 g each) with normal eardrums and Preyer reflexes were
      used for the experiment. Inner ear pressure was modified by two approaches-
      directly via a tube placed in the inner ear (n=5) and indirectly via a tube
      placed in the subaracnoid space (n=5). Slow uniform pressure (microl/min) was
      infused until constant pressure was maintained. At this time, an artificial
      endolymph or perilymph was injected with a constant pressure of 100 and 300 mm
      H2O. We measured the umbo velocity using a LDV. RESULTS: A positive pressure load
      decreased the umbo vibration at low frequencies but did not change the umbo
      vibration at mid and high frequencies. The umbo velocity had a greater reduction
      for an endolymphatic pressure load than for a perilymphatic pressure load. The
      largest change in velocity was noted at a frequency of 0.1 kHz. There was no
      significant change in velocity at higher frequencies, except for 5 kHz.
      CONCLUSION: LDV is a good tool to analyze middle ear function and it has the
      potential indirectly to diagnose an increase in endolymphatic or perilymphatic
      pressure.

PMID- 19117617
TI  - In vivo experiments for the evaluation of genotoxic and cytotoxic effects of
      Triclosan in Zebra mussel hemocytes.
AB  - In this work, we investigated the possible genotoxic and cytotoxic effects of the
      antibacterial agent Triclosan in hemocytes of the freshwater bivalve Zebra mussel
      (Dreissena polymorpha). For this study, we used several biomarkers for in vivo
      experiments (96h of exposure) carried out at three possible environmental
      Triclosan concentrations (1, 2, 3nM). We used the single cell gel electrophoresis
      (SCGE) assay, the micronucleus test (MN test) and the measure of the apoptotic
      frequency (Halo assay) to measure the genotoxic potential of Triclosan, and the
      neutral red retention assay (NRRA) as a measure of lysosomal membrane stability
      to identify general cellular stress. We observed significant increases in all of
      the genotoxic biomarkers examined as early as 24h after initial exposure, as well
      as a clear destabilization of lysosomal membranes (after 48h), indicating that
      this chemical is potentially dangerous for the entire aquatic biocoenosis. A
      comparison of these in vivo data with existing data from in vitro experiments
      allowed us to suggest possible mechanisms of action for Triclosan in this
      bivalve. Although further studies are needed to confirm the possible modes of
      action, our study is the first to report on the effects of this widespread
      antibiotic on freshwater invertebrates.

PMID- 19117618
TI  - Satisfaction of the complete denture wearers related to various factors.
AB  - All dentists who have worked with complete denture wearers know that patient
      satisfaction is not based only on the technical quality of the dentures. The aim
      of this study was at assessing the effect of gender, the number of the dentures
      used before, the length of time of denture usage, education and age on the
      satisfaction of the complete denture wearers. The students of the Dental Faculty
      of Marmara University (Turkey) made new dentures for 342 patients who were asked
      to participate in the investigation. The subjects (137 men and 205 women) were 39
      89 years of age with a mean of 61.62 years. The attitude toward dentures in
      general was measured by means of 11 items of a questionnaire. The 10 main
      questions of the questionnaire were answered by the participants, and quantified
      on a 7-point scale, while the 11th issue (general satisfaction) was evaluated on
      a scale of 1-10. All main factors were also estimated in subgroups. For example,
      the education was analyzed in 4 subgroups, the time of denture usage was divided
      into two subgroups (below and above 3 years) and the number of dentures used
      before was also taken as up to 3 or more than 3 dentures. The age of the subjects
      was taken in 3 subgroups: 40-55, 56-65 and >65 years. One-way ANOVA, Tukey and
      Student t-tests were used to evaluate the answers to the questionnaire. Our
      patients displayed statistically significant differences only in the topics of
      their ability of cleaning their dentures, due to education and number of
      previously used dentures.

PMID- 19117619
TI  - Effect of successful parathyroidectomy on 24-hour ambulatory blood pressure in
      patients with primary hyperparathyroidism.
AB  - OBJECTIVE: The pathogenesis of hypertension in patients with primary
      hyperparathyroidism (PHPT) is unclear, and the prevailing opinion is that
      parathyroidectomy does not affect the blood pressure (BP). Most previous studies
      have been based on BP measurements at rest in a clinical setting. The aim of this
      study was to get additional information by 24-hour ambulatory measurements.
      DESIGN AND PATIENTS: Forty-nine consecutive patients with PHPT (age 63+/-12
      years, 44 women) were examined before and 6 months after curative parathyroid
      surgery. MEASUREMENTS: Serum concentrations of calcium and PTH, and 24-hour
      ambulatory mean, minimum, and maximum systolic (S) and diastolic BP, and mean
      arterial BP. RESULTS: On average, the patients showed no BP change after
      parathyroidectomy. However, those with a history of hypertension (n=20) showed
      generally increased BP values after parathyroidectomy, with significantly
      increased minimum and average SBP (P=0.02 and P=0.04, respectively), whereas
      patients without a history of hypertension (n=29) showed unchanged or slightly
      reduced BP values after parathyroidectomy, with significantly decreased maximum
      SBP (P=0.04). Serum concentrations of PTH and calcium were not significantly
      related to any of the BP variables measured. CONCLUSIONS: The novel finding that
      patients with both PHPT and hypertension may show increased BP after
      parathyroidectomy warrants intensified BP control postoperatively in these
      patients, and motivates early treatment of PHPT in order to prevent the
      development of complicating hypertension.

PMID- 19117620
TI  - Pulmonary vein and atrial wall pathology in human total anomalous pulmonary
      venous connection.
AB  - BACKGROUND: Normally, the inside of the left atrial (LA) body and pulmonary veins
      (PVs) is lined by vessel wall tissue covered by myocardium. In total anomalous
      pulmonary venous connection (TAPVC), no connection of the PVs with the LA body
      exists. These veins have an increased incidence of PV stenosis. We describe the
      consequences of the absent connection for the histopathology of the wall of the
      LA body and the PVs, and hypothesize on a mechanism predisposing to PV stenosis.
      METHODS AND RESULTS: In 10 human neonates with TAPVC, the wall of the LA body and
      PVs were studied using histological and immunohistochemical techniques. As
      controls, 2 normal neonatal and adult hearts and 5 neonatal hearts with partial
      anomalous venous connection (PAPVC) or situs inversus were studied. In hearts
      with TAPVC no vessel wall tissue was found in the LA body and its myocardial
      layer was hypoplastic. No myocardial sleeve was found around the abnormally
      draining PVs. In hearts with PAPVC, only the non-LA draining PV lacked myocardial
      covering, whereas in situs inversus PVs connecting to the right-sided LA, were
      normally myocardialized. CONCLUSION: An open connection of the PVs with the
      morphological LA is necessary for the presence of vessel wall tissue in the LA
      and myocardialization of the PVs. Absence of myocardium covering the PVs is
      hypothesized to enhance susceptibility to PV stenosis and prevent onset of PV
      originating arrhythmias. The embryonic posterior heart field may be responsible
      for the abnormal myocardialization and smooth muscle cell formation in TAPVC.

PMID- 19117621
TI  - May emergency hypertension be reason of spontaneous coronary artery dissection?
AB  - Spontaneous coronary artery dissection is an uncommon clinical condition. It has
      most often been described in healthy peripartum women with no risk factors for
      atherosclerosis. We present a patient of a 40 year-old man with emergency
      hypertension. His coronary angiography revealed dissection of the left anterior
      descending coronary artery which was treated with angioplasty and stenting. We
      postulate that emergency hypertension may be a reason of spontaneous coronary
      artery dissection.

PMID- 19117622
TI  - Revelation of Brugada electrocardiographic pattern during a febrile state.
AB  - The prevalence of the Brugada-type ECG and its natural history are still unclear.
      The Brugada syndrome is usually identified by a characteristic Brugada-type ECG
      that consists of ST elevation of a coved type in the precordial leads V1 to V3
      and ventricular fibrillation that can lead to sudden cardiac death, although
      affected individuals may have a normal ECG. Mutations in the cardiac sodium
      channel gene SCN5A, which encodes the alpha-subunit of the human cardiac voltage
      dependent Na+ channel (Na(v)1.5), are identified in 15-30% of patients with
      Brugada syndrome. Most SCN5A mutations lead to a 'loss-of-function' phenotype,
      reducing the Na+ current during the early phases of the action potential. Several
      nongenetic factors have been mentioned in the literature as possible inductors of
      the ECG pattern resembling Brugada syndrome. As such, a Brugada-type ECG may
      appear in some patients during febrile states and in those who are under the
      influence of cocaine and pharmaceutical drugs that have a sodium channel-blocking
      effect. It has been also reported that chest pain and ST elevation Brugada
      pattern occur during febrile states. We present a case of revelation of Brugada
      pattern in a 61-year-old Italian man complaining of pain in the left hipocondrium
      during a febrile state. Also this report confirms that Brugada pattern should be
      considered as one of differential diagnoses when we examine the patients during a
      febrile state.

PMID- 19117623
TI  - A case of paclitaxel-eluting stent fracture after successful recanalization of
      chronic total occlusion using a retrograde approach.
AB  - Drug-eluting stents (DES) have greatly reduced the possibility of in-stent
      restenosis by inhibiting neointimal growth. But recently stent fracture has
      emerged as a complication. We describe a case of paclitaxel-eluting stent
      fracture after successful percutaneous coronary intervention (PCI) for chronic
      total occlusion using retrograde approach.

PMID- 19117624
TI  - Death caused by simultaneous subacute stent thrombosis of sirolimus-eluting
      stents in left anterior descending artery and left circumflex artery.
AB  - Simultaneous drug-eluting stent thrombosis in multivessel disease is a low
      incidence, but could cause lethal clinical event. We report a case with death
      caused by simultaneous subacute stent thrombosis of sirolimus-eluting stents in
      the proximal left anterior descending artery and in the proximal left circumflex
      artery.

PMID- 19117625
TI  - Effect of obesity on coronary artery plaque using 64 slice multidetector cardiac
      computed tomography angiography.
AB  - Patients with a coronary artery calcification score (CACS) of zero and an
      intermediate risk of coronary artery disease have been shown to have a low
      prevalence of non-calcified coronary artery plaque (NCP). 181 consecutive
      patients with CAC 'zero', undergoing cardiac computed tomography angiography
      (CCTA) angiography at our center were evaluated. Presence of detectable NCP on
      CCTA in these patients was 13.8%. Mild non-obstructive disease (<30% and limited
      to one segment) was present in 76% of patients while only one patient (0.6%) had
      significant stenosis (>50%). Traditional risk factors were not found to be
      associated with the presence of NCP. However higher body mass index (BMI) was
      strongly found to be associated with NCP (31.6 in patients with NCP vs. 27.6
      kg/m(2) in patients without NCP, p<.05). Obesity was 2.76 times more likely to be
      associated with NCP as compared to normal BMI (p<0.05).

PMID- 19117626
TI  - A new treatment modality in management of patients with cardiac syndrome X:
      enhanced external counterpulsation.

PMID- 19117627
TI  - Designing strategies to control coronary atherosclerosis using a new model.

PMID- 19117628
TI  - Macro-CK in 82 year old woman. A case report.
AB  - We report the case of an 82-year old female patient admitted to the emergency
      department after fainting episode, low blood pressure, and arrhythmia. The
      patient reported a watery diarrhea of 3 weeks duration. Extremely high total
      creatinine kinase (CK) and CK-MB activity but normal troponin level were
      measured. Laboratory investigation showed the presence of macro form of CK.
      Abnormal CK and CK-MB activity was still measured eight months after patient
      episode. Due to unexplained watery diarrhea during three weeks before admission
      several tests for presence of autoantibodies were performed. The only positive
      result has been noted for anti-Saccharomyces cerevisiae antibodies (ASCA), IgG
      isotype.

PMID- 19117629
TI  - Ecophysiological factor effect on growth rate, lag phase and ochratoxin A
      production by Aspergillus niger aggregate strains on irradiated peanut seeds.
AB  - The aims of this study were to evaluate the effects of water activity,
      temperature, incubation time and their interactions on lag phase, growth rate and
      ochratoxin A (OTA) production by strains belonging to the Aspergillus niger
      aggregate on irradiated peanut seeds. In the temperature and water activity range
      assayed, the optimal conditions of growth for RCP42 and RCP176 strains on
      irradiated peanut seeds were 0.995 a(w) and 30 degrees C being the growth rates
      of 12.4 and 14.6 mm/day, respectively. The maximum OTA production occurred at
      0.973 a(w) and 25 degrees C for both strains assayed; whereas the minimum OTA
      production was obtained at 0.951 a(w) and 15 degrees C, at 14 and 21 days of
      incubation for RCP42 and RCP176 strains, respectively. The amount of OTA
      accumulated during 21 days assayed by both strains varied from 6.5 to 460
      microg/g and from 10 to 210 microg/g with mean levels of 119.2 and 97.5 microg/g
      for RCP42 and RCP176 strains, respectively. The variance analysis (ANOVA)
      revealed that OTA concentration produced by RCP42 strain was significantly
      (p<0.0001) greater than that produced by RCP176 strain. If the strains with which
      the experiments were carried out were representative of the Aspergillus niger
      aggregate toxigenic species and the water activity in peanut seeds stored at
      0.910 or lower was maintained, OTA production would be reduced during at least 21
      days at variable temperatures.

PMID- 19117630
TI  - Association of fasting and post-prandial hyperglycemia on the risk of
      cardiovascular and all-cause death among non-diabetic Chinese.
AB  - The role of post-prandial glucose on cardiovascular risk among Chinese adults
      without diabetes was investigated. In a median follow-up of 3.5 years on 16,590
      participants, 95 cardiovascular deaths were found. The relative risk in the
      highest quintile post-prandial glucose was 1.61 (P for trend, 0.05) for
      cardiovascular death.

PMID- 19117632
TI  - Two cases of type 1 diabetic women with diabetic ketoacidosis presenting as
      alkalaemia.
AB  - We report two type 1 diabetic patients with diabetic ketoacidosis accompanied by
      alkalaemia. Twenty-three cases have been reported to date, and the main causes
      for alkalaemia were vomiting, alkali ingestion, and diuretics use. Our report
      indicated that poorly controlled diabetic patients who already had autonomic
      neuropathy are at risk.

PMID- 19117631
TI  - Risk factors for developing osteomyelitis in patients with diabetic foot wounds.
AB  - AIMS: Osteomyelitis worsens the prognosis in the diabetic foot, but predisposing
      factors remain largely undefined. In a prospectively followed cohort we assessed
      risk factors for developing osteomyelitis. METHODS: We enrolled consecutive
      persons with diabetes who presented to a managed-care diabetes disease management
      program. The patients underwent standardized assessments. We monitored for all
      foot complications, defined infections by criteria consistent with International
      Working Group guidelines, and defined osteomyelitis as a positive culture from a
      bone specimen. RESULTS: 1666 persons were enrolled, 50% male, mean age 69 years.
      Over a mean of 27.2 months of follow-up, 151 patients developed foot infections,
      30 (19.9%) of which involved bone. Independent risk factors for osteomyelitis
      were: wounds that extended to bone or joint (relative risk [RR]=23.1), previous
      history of a wound prior to enrollment (RR=2.2), and recurrent or multiple wounds
      during the study period (RR=1.9). CONCLUSIONS: In this study population, managed
      in a specialized diabetic foot care center, the results suggest that independent
      risk factors for developing osteomyelitis are deep, recurrent and multiple
      wounds. These results may help clinicians target their efforts at diagnosing foot
      osteomyelitis to the highest risk patients.

PMID- 19117633
TI  - NO-mediated cytotoxicity contributes to multiple low-dose streptozotocin-induced
      diabetes but not to NOD diabetes.
AB  - Type 1 diabetes (T1D) is caused mostly by autoimmune destruction of pancreatic
      beta-cells, the precise mechanism of which remains unclear. Two major effector
      mechanisms have been proposed: direct cell-mediated and indirect cytokine
      mediated cytotoxicity. Cytokine-mediated beta-cell destruction is presumed mainly
      caused by NO production. To evaluate the role of iNOS expression in T1D, this
      study used a novel iNOS inhibitor ONO-1714. ONO-1714 significantly reduced
      cytokine-mediated cytotoxicity and NO production in both MIN6N9a cells and
      C57BL/6 islets in the presence of IL-1beta, TNF-alpha, and IFN-gamma. To evaluate
      whether NO contributes to diabetes progression in vivo, ONO-1714 was administered
      to four different mouse models of autoimmune diabetes: multiple low-dose STZ
      (MLDS)-induced C57BL/6, CY-induced, adoptive transfer and spontaneous NOD
      diabetes. Exposure to STZ in vitro induced NO production in MIN6N9a cells and
      C57BL/6 islets, and in vivo injection of ONO-1714 to MLDS-treated mice
      significantly reduced hyperglycemia and interestingly, led to complete
      suppression of cellular infiltration of pancreatic islets. In contrast, when ONO
      1714 was injected into spontaneous NOD mice and CY-induced and adoptive transfer
      models of NOD diabetes, overt diabetes could not be inhibited in these models.
      These findings suggest that NO-mediated cytotoxicity significantly contributes to
      MLDS-induced diabetes but not to NOD diabetes.

PMID- 19117634
TI  - Depression is greater in non-English speaking hospital outpatients with type 2
      diabetes.
AB  - This study aimed to compare the prevalence of depression and anxiety in English
      (ES) and non-English speaking (NES) hospital outpatients with type 2 diabetes.
      Overall, depression and/or anxiety were present in 31% of patients. The
      prevalence of depression was significantly higher in NES than ES patients
      (p=0.03).

PMID- 19117635
TI  - What does it mean to trust a health system? A qualitative study of Canadian
      health care values.
AB  - OBJECTIVES: We used a qualitative empirical study of Canadians' values toward
      their health system to develop more meaningful conceptualizations of trust and
      health systems that can inform the pursuit of more trustworthy health systems.
      METHODS: We convened nine focus groups in three Canadian cities in 2002 and 2004
      in conjunction with a national public opinion telephone survey of Canadians'
      attitudes and values toward their health system. Health system trust emerged as a
      significant theme in focus group discussions and was investigated using a
      modified grounded theory approach. FINDINGS: Respondents construct cleavages and
      alliances to position themselves in relation to different features of the trusted
      health system. The health system and Canadian Medicare are identified sources of
      trust just as are individual health care providers. Core to the trust
      relationship is the experience of vulnerability which provides the impetus for
      placing trust (in providers, governments and health systems) or seeds distrust,
      mistrust and resilience in the same. CONCLUSIONS: We offer a more robust
      conceptualization of what it means to trust a health system. Policy maker efforts
      to intervene to restore lost trust could usefully be informed by these findings.

PMID- 19117636
TI  - Perceptions of medical malpractice and medical malpractice reform among first-
      and fourth-year medical students.
AB  - OBJECTIVES: Comparison of first- and fourth-year medical student perceptions of
      the U.S. medical malpractice system and their disposition toward reform, and
      examination of the relationship between school year and other potential
      correlates of these perceptions. METHODS: Data derived from 109 students at Brown
      Medical School who responded to a 2006 web-based survey of attitudes and
      background characteristics. We report student perceptions stratified by medical
      school year. We use Mann-Whitney U and chi2 tests to examine the correlates of
      perceptions and linear regression to examine these in a multivariate context.
      RESULTS: There were no significant differences in the dispositions of first- and
      fourth-year students toward the current system (p> or =0.05). However, fourth
      year students were more likely to favor screening panels for malpractice cases
      (82.2% vs. 70.4%) and capping pain and suffering damages (68.9% vs. 55.2%) (both
      p<0.05). Multivariate results reveal greater concern about malpractice among
      students intending to specialize in high-risk areas (both p<0.001). Bivariate
      results reveal greater concern among students with lawyer relatives (p<0.05).
      CONCLUSIONS: First- and fourth-year students had overwhelmingly negative
      perceptions of the medical malpractice system. This implies attitudes toward
      malpractice are formed before medical school, with intended specialty and other
      background characteristics more negatively influencing students' views.

PMID- 19117637
TI  - Design, development, exploitation and assessment of a Cardiology Web PACS.
AB  - Healthcare institutions are increasingly turning to digital medical imaging
      systems to promote better diagnosis and treatment of their patients. The
      implementation of the Picture Archiving and Communication System (PACS) clearly
      contributes to an increase in the productivity of health professionals. However,
      despite the amount of research that has been done in the past two decades, there
      are still several technological hurdles that hinder the wide adoption of PACS in
      the Web environment. In this paper, we present a Web-enabled PACS that through
      the inclusion of several DICOM services and compression methods promotes medical
      image availability and greater accessibility to users.

PMID- 19117638
TI  - Plasminogen activator inhibitor variants PAI-1 A15T and PAI-2 S413C influence
      lung cancer prognosis.
AB  - The plasminogen pathway plays an important role in the behavior of many tumors
      including lung cancer. Hence genetic variants encoding plasminogen activator
      (PLAU), plasminogen receptor (PLAUR), plasminogen activator inhibitor 1 (PAI-1)
      and plasminogen activator inhibitor 2 (PAI-2) may contribute to lung cancer
      prognosis. To investigate this proposition we genotyped PAI-1 A15T, PLAU L141P,
      PLAUR L317P and PAI-2 S413C variants in 698 patients with lung cancer, 522 with
      non-small cell (NSCLC) and 176 with small cell lung cancer (SCLC). PAI-1 A15T was
      significantly associated with overall survival (OS), with carriers of variant
      alleles having a worse prognosis (hazard ratio (HR)=1.14; 95% confidence interval
      [CI]: 1.03-1.26). An association was also detected between OS in NSCLC and
      carrier status for PAI-2 413C (HR=1.13; 95% CI: 1.01-1.24). These common genetic
      variants identified warrant further evaluation as promising prognostic markers of
      patient outcome.

PMID- 19117639
TI  - Modelling the fate of styrene in a mixed petroleum hydrocarbon plume.
AB  - Severe petroleum hydrocarbon contamination (styrene and the BTEX compounds:
      benzene, toluene, ethylbenzene and the isomers of xylene) from leaking sewers was
      detected in a Quaternary aquifer below a chemical plant in the Padana Plain,
      Italy. From 1994, active pump and treat remediation has been employed. The site
      is bordered by canals which, in combination with variable pumping rates and
      groundwater flow directions, control groundwater levels. In this study we sought
      to determine the fate of styrene at the site within a mixed styrene/BTEX plume
      where the hydraulic boundaries induced strong seasonal variations in flows. In
      order to determine the fate of styrene, detailed field investigations provided
      intensive depth profile information. This information was then incorporated into
      a staged flow and reactive transport modelling. Three sets of measurements were
      obtained from sampling multilevel samplers (MLSs) under different hydraulic
      conditions at the site. These included measurements of BTEX, styrene, all major
      ions, pH and redox potential. A three-dimensional transient flow model was
      developed and calibrated to simulate an unconfined sandy aquifer with a variable
      flow field. Subsequently a reactive, multi-component transport model was employed
      to simulate the fate of dissolved BTEX and styrene along a selected flow line at
      the site. Each petroleum hydrocarbon compound was transported as independent
      species. Different, kinetically controlled degradation rates and a toxicity
      effect were simulated to explain the observed, selective degradation of
      pollutants in groundwater. Calibration of the model was accomplished by
      comparison with the three different sets of measurements obtained from the MLS
      devices. The results from various scenarios show that the detailed simulation of
      geochemical changes can be very useful to improve the site's conceptual model.

PMID- 19117640
TI  - Unexpected localization of a lipid transfer protein in germinating sunflower
      seeds.
AB  - Plant lipid transfer proteins (LTPs) are low-molecular-mass proteins whose
      biological function still remains elusive. They are synthesized with a signal
      peptide that drives them to the secretory pathway. We have previously described
      the occurrence of an apoplastic LTP named Ha-AP10, present in sunflower seeds.
      Using a biochemical approach we now demonstrate that a fraction of Ha-AP10 is
      perispherically bound to membranes of germinating seeds. Purification of plasma
      membranes revealed the presence of Ha-AP10 in this fraction.
      Fluorimmunolocalization studies on germinating sunflower seeds demonstrated that
      in addition to the apoplastic and plasma membrane localization, Ha-AP10 is also
      present intracellularlly associated to unidentified structures. This varied
      distribution of Ha-AP10 in sunflower seeds may give novel clues to understand the
      role of LTPs in seed physiology.

PMID- 19117642
TI  - Phenylpyrrole derivatives as neural and inducible nitric oxide synthase (nNOS and
      iNOS) inhibitors.
AB  - We have previously described a series of 3-phenyl-4,5-dihydro-1H-pyrazole
      derivatives as moderately potent nNOS inhibitors. As a follow up of these
      studies, several new 5-phenyl-1H-pyrrole-2-carboxamide derivatives have been
      synthesized, and their biological evaluation as in vitro inhibitors of both
      neural and inducible Nitric Oxide Synthase (nNOS and iNOS) is described. Some of
      these compounds show good iNOS/nNOS selectivity and the more potent compounds 5
      (2-aminophenyl)-1H-pyrrole-2-carboxilic acid methylamide (QFF205) and
      cyclopentylamide (QFF212) have been tested as regulators of the in vivo nNOS and
      iNOS activity. Both compounds prevented the increment of the inducible NOS
      activity in both cytosol (iNOS) and mitochondria (i-mtNOS) observed in the MPTP
      model of Parkinson's disease.

PMID- 19117641
TI  - Epigenetic changes in Alzheimer's disease: decrements in DNA methylation.
AB  - DNA methylation is a vital component of the epigenetic machinery that
      orchestrates changes in multiple genes and helps regulate gene expression in all
      known vertebrates. We evaluated immunoreactivity for two markers of DNA
      methylation and eight methylation maintenance factors in entorhinal cortex layer
      II, a region exhibiting substantial Alzheimer's disease (AD) pathology in which
      expression changes have been reported for a wide variety of genes. We show, for
      the first time, neuronal immunoreactivity for all 10 of the epigenetic markers
      and factors, with highly significant decrements in AD cases. These decrements
      were particularly marked in PHF1/PS396 immunoreactive, neurofibrillary tangle
      bearing neurons. In addition, two of the DNA methylation maintenance factors,
      DNMT1 and MBD2, have been reported also to interact with ribosomal RNAs and
      ribosome synthesis. Consistent with these findings, DNMT1 and MBD2, as well as
      p66alpha, exhibited punctate cytoplasmic immunoreactivity that co-localized with
      the ribosome markers RPL26 and 5.8s rRNA in ND neurons. By contrast, AD neurons
      generally lacked such staining, and there was a qualitative decrease in RPL26 and
      5.8s rRNA immunoreactivity. Collectively, these findings suggest epigenetic
      dysfunction in AD-vulnerable neurons.

PMID- 19117643
TI  - Metastasis of carcinosarcoma of oesophagus to gastrostomy site.
AB  - Patients with head and neck cancers need a percutaneous endoscopic gastrosotomy
      (PEG) before start of treatment to ensure adequate nutrition because worsening
      dysphagia during chemo radiation [Nicholson FB, Korman MG, Richardson MA.
      Percutaneous endoscopic gastrostomy: a review of indications, complications and
      outcome. J. Gastroenterol Hepatol 2000; 15: 21-5; Beer KT, Krause KB, Zuercher T,
      Stanga Z. Early percutaneous endoscopic gastrostomy insertion maintains
      nutritional state in patients with aerodigestive tract cancer. Nutr Cancer 2005;
      52: 29-34.]. However implantation of original tumor to the gastrostomy exit site
      is rare but serious complication of this procedure and here we report a case of
      PEG site metastasis along with relevant review of literature.

PMID- 19117644
TI  - Why do women request caesarean section in a normal, healthy first pregnancy?
AB  - BACKGROUND AND CONTEXT: a growing number of childbearing women are reported to
      prefer a caesarean section in the absence of a medical reason. Qualitative
      research describing factors influencing this preference in pregnant women is
      lacking. OBJECTIVE: to describe Australian women's request for caesarean section
      in the absence of medical indicators in their first pregnancy. DESIGN:
      advertisements were placed in local newspapers inviting women to participate in a
      telephone interview exploring women's experience of caesarean section. Thematic
      analysis was used to analyse data. SETTING: two states of Australia: Queensland
      and Western Australia. PARTICIPANTS: a community sample of women (n=210)
      responded to the advertisements. This paper presents the findings elicited from
      interviews conducted with 14 women who requested a caesarean section during their
      first pregnancy in the absence of a known medical indication. FINDINGS:
      childbirth fear, issues of control and safety, and a devaluing of the female body
      and birth process were the main themes underpinning women's requests for a non
      medically-indicated caesarean section. Women perceived that medical discourses
      supported and reinforced their decision as a 'safe' and 'responsible' choice. KEY
      CONCLUSIONS AND RECOMMENDATIONS FOR PRACTICE: these findings assist women and
      health professionals to better understand how childbirth can be constructed as a
      fearful event. In light of the evidence about the risks associated with surgical
      birth, health-care professionals need to explore these perceptions with women and
      develop strategies to promote women's confidence and competence in their ability
      to give birth naturally.

PMID- 19117645
TI  - Discussions of findings from a Cochrane review of midwife-led versus other models
      of care for childbearing women: continuity, normality and safety.

PMID- 19117646
TI  - Enhancing safety in the maternity services: a greater role for midwife-led care?

PMID- 19117647
TI  - The importance of ammonium mobility in nitrogen-impacted unfertilized grasslands:
      a critical reassessment.
AB  - The physico-chemical absorption characteristics of ammonium-N for 10 soils from 5
      profiles in York, UK, show its high potential mobility in N deposition-impacted,
      unfertilized, permanent grassland soils. Substantial proportions of ammonium-N
      inputs were retained in the solution phase, indicating that ammonium
      translocation plays an important role in the N cycling in, and losses from, such
      soils. This conclusion was further supported by measuring the ammonium-N leaching
      from intact plant/soil microcosms. The ammonium-N absorption characteristics
      apparently varied with soil pH, depth and soil texture. It was concluded for the
      most acid soils especially that ammonium-N leached from litter horizons could be
      seriously limiting the capacity of underlying soils to retain ammonium. Contrary
      to common opinion, more attention therefore needs to be paid to ammonium leaching
      and its potential role in biogeochemical N cycling in semi-natural soil systems
      subject to atmospheric pollution.

PMID- 19117648
TI  - Effects of fulvic acid concentration and origin on photodegradation of polycyclic
      aromatic hydrocarbons in aqueous solution: importance of active oxygen.
AB  - With an Xe arc lamp house as simulated sunlight, the influences of fulvic acid
      (FA) concentration and origins on photodegradation of acenaphthene, fluorine,
      phenanthrene, fluoranthene and pyrene in aqueous solution have been studied.
      Similar effects of FAs, collected from five places around China, on polycyclic
      aromatic hydrocarbon (PAH) photodegradation have been observed. Active oxygen was
      of significance in PAH photodegradation with the presence of FAs. For systems
      with 1.25 mg L(-1) FAs, the contributions of 8*OH to PAH photodegradation rates
      were from 33% to 69%. FAs had two opposite effects, i.e., stimulating the
      generation of active oxygen and advancing PAH photodegradation; competing with
      PAHs for energy and photons and restraining PAH photodegradation. Generally,
      photodegradation rates of the 5 PAHs decreased with the increase of FAs
      concentration; except fluoranthene and pyrene were advanced in solutions with low
      FA concentration. The influences of FA concentration on PAH photodegradation were
      more significant than FA origin.

PMID- 19117649
TI  - Production and sedimentation of peptide toxins nodularin-R and microcystin-LR in
      the northern Baltic Sea.
AB  - This seven-year survey was primarily targeted to quantification of production of
      nodularin-R (NOD-R), a cyclic pentapeptide hepatotoxin, in Baltic Sea
      cyanobacteria waterblooms. Additionally, NOD-R and microcystin-LR (MC-LR; a
      cyclic heptapeptide toxin) sedimentation rates and NOD-R sediment storage were
      estimated. NOD-R production (70-2450 microg m(-3); approximately 1 kg km(-2) per
      season) and sedimentation rates (particles; 0.03-5.7 microg m(-2)d(-1);
      approximately 0.3kg km(-2) per season) were highly variable over space and time.
      Cell numbers of Nodularia spumigena did not correlate with NOD-R quantities.
      Dissolved NOD-R comprised 57-100% of total NOD-R in the predominantly senescent,
      low-intensity phytoplankton blooms and seston. Unprecedentedly intensive MC-LR
      sedimentation (0.56 microg m(-2)d(-1)) occurred in 2004. Hepatotoxin
      sedimentation rates highly exceeded those of anthropogenic xenobiotics. NOD-R
      storage in surficial sediments was 0.4-20 microg kg(-1) ( approximately 0.1 kg
      km(-2)). Loss of NOD-R within the chain consisting of phytoplankton, seston and
      soft sediments seemed very effective.

PMID- 19117650
TI  - Heavy metal exposure in large game from a lead mining area: effects on oxidative
      stress and fatty acid composition in liver.
AB  - The Pb mining area of the valley of Alcudia and the Sierra Madrona mountains (S.
      Spain) has been exploited intermittently for over 2100 years, since Roman
      occupation and up until the late 1900s. Red deer (n=168) and wild boar (n=58)
      liver and bone (metacarpus) were analyzed for Pb, Zn, Cu, Cd, As and Se. Lipid
      peroxidation, total and oxidized glutathione (GSH), superoxide dismutase (SOD),
      GSH peroxidase (GPX) and fatty acid composition were studied in liver of red
      deer. The concentrations of Pb in liver and bone of red deer and wild boar were
      higher in the mining area than in the control area, and higher in the wild boar
      than red deer, but well below the level associated with clinical signs of Pb
      poisoning. Liver levels of Cu, Cd and Se were also higher in red deer from the
      mining area. Red deer from the mining area had 39% less total GSH than in the
      control area. The percentage of docosahexaenoic acid in liver of red deer from
      the mining area was 16% lower than in the control area.

PMID- 19117651
TI  - Detection of DDT and its metabolites in two estuaries of South China using a SPME
      based device: first report of p,p'-DDMU in water column.
AB  - A solid-phase microextration-based sampling method was employed to determine the
      concentrations of 1,1,1-trichloro-2,2-bis(p-chlorophenyl)ethane (DDT) and its
      metabolites, 1,1-dichloro-2,2-bis(p-chlorophenyl)ethane (DDD), 1,1-dichloro-2,2
      bis(p-chlorophenyl)ethene (DDE) and 1-chloro-2,2-bis(p-chlorophenyl)ethene
      (DDMU), in two estuarine bays, Daya Bay and Hailing Bay, of South China. Six DDT
      components including p,p'-DDT, o,p'-DDD, p,p'-DDD, o,p'-DDE, p,p'-DDE, and p,p'
      DDMU were detected in Hailing Bay, while only p,p'-DDD was found in Daya Bay.
      p,p'-DDD was the most abundant DDT component in both bays, sharply different from
      the previous finding in the water column of the Palos Verdes Shelf, California,
      USA that p,p'-DDE was prevalent. In addition, the occurrence of p,p'-DDMU (with a
      range of 0.047-0.21 ng/L in Hailing Bay) has not been reported around the globe,
      and its presence in our study region appeared to stem from dehydrochlorination of
      p,p'-DDD, favored under aerobic conditions, but further investigations are
      clearly needed to confirm the mechanism for generation of DDMU in estuarine
      environments.

PMID- 19117652
TI  - Sediment processes and mercury transport in a frozen freshwater fluvial lake
      (Lake St. Louis, QC, Canada).
AB  - An open-bottom and a closed-bottom mesocosm were developed to investigate the
      release of mercury from sediments to the water column in a frozen freshwater
      lake. The mesoscosms were deployed in a hole in the ice and particulate mercury
      (Hg(P)) and total dissolved mercury (TDHg) were measured in sediments and in
      water column vertical profiles. In addition, dissolved gaseous mercury (DGM) in
      water and mercury water/airflux were quantified. Concentrations of TDHg, DGM, and
      mercury flux were all higher in the open-bottom mesocosm than in the closed
      bottom mesocosm. In this paper we focus on the molecular diffusion of mercury
      from the sediment in comparison with the TDHg accumulation in the water column.
      We conclude that the molecular diffusion and sediment resuspension play a minor
      role in mercury release from sediments suggesting that solute release during
      ebullition is an important transport process for mercury in the lake.

PMID- 19117653
TI  - The impact of semiconductor, electronics and optoelectronic industries on
      downstream perfluorinated chemical contamination in Taiwanese rivers.
AB  - This study provides the first evidence on the influence of the semiconductor and
      electronics industries on perfluorinated chemicals (PFCs) contamination in
      receiving rivers. We have quantified ten PFCs, including perfluoroalkyl
      sulfonates (PFASs: PFBS, PFHxS, PFOS) and perfluoroalkyl carboxylates (PFCAs:
      PFHxA, PFHpA, PFOA, PFNA, PFDA, PFUnA, PFDoA) in semiconductor, electronic, and
      optoelectronic industrial wastewaters and their receiving water bodies (Taiwan's
      Keya, Touchien, and Xiaoli rivers). PFOS was found to be the major constituent in
      semiconductor wastewaters (up to 0.13 mg/L). However, different PFC distributions
      were found in electronics plant wastewaters; PFOA was the most significant PFC,
      contributing on average 72% to the effluent water samples, followed by PFOS (16%)
      and PFDA (9%). The distribution of PFCs in the receiving rivers was greatly
      impacted by industrial sources. PFOS, PFOA and PFDA were predominant and
      prevalent in all the river samples, with PFOS detected at the highest
      concentrations (up to 5.4 microg/L).

PMID- 19117654
TI  - Mass flows of endocrine disruptors in the Glatt River during varying weather
      conditions.
AB  - This study focused on the occurrence and behaviour in wastewater and surface
      waters of several phenolic endocrine disrupting compounds (EDCs) including
      parabens, alkylphenolic compounds, phenylphenol (PhP) and bisphenol A (BPA).
      Analytical procedures using solid-phase-extraction and LC-MS/MS techniques were
      applied to samples of influents and effluents of wastewater treatment plants
      (WWTPs) discharging into the Glatt River (Switzerland) as well as to river water
      samples. A mass flow analysis provided insight into the main sources and the fate
      of these contaminants during different weather conditions. Concentrations in
      influents were in the low microg/L range for most analytes. Removal of parabens
      in the WWTPs was mostly above 99%. Nonylphenol polyethoxylates (A(9)PEO) removal
      amounted to 98%, but in some cases nonylphenoxy acetic acid (A(9)PEC) or
      nonylphenols (NP) were formed. In effluents, concentrations were highest for the
      A(9)PEC, A(9)PEO and NP. Concentrations in river water were in the high ng/L
      range for alkylphenolic compounds and in the low ng/L range for BPA, PhP and the
      parabens. During the sampling period, in which several rain events occurred, both
      water flows and mass flows varied strongly. Mass flows in WWTP effluents and in
      the river increased with increasing water flows for most compounds indicating
      that higher water flows do not lead necessarily to a proportional dilution of the
      pollutants. Throughout the low water flow period, mass flows predicted from the
      known inputs were similar to the actual mass flows at the end of the river for
      most analytes. For none of the EDCs, significant in-stream removal could be
      observed. In the periods with high water flows, mass flows in the river were much
      higher than can be explained by the initially defined sources. Discharge of
      untreated wastewater influent into the river was assessed as an additional
      source. Adding this source improved the mass balance for some, but not all of the
      analytes.

PMID- 19117655
TI  - Responses of herbaceous plants to urban air pollution: effects on growth,
      phenology and leaf surface characteristics.
AB  - Vehicle exhaust emissions are a dominant feature of urban environments and are
      widely believed to have detrimental effects on plants. The effects of diesel
      exhaust emissions on 12 herbaceous species were studied with respect to growth,
      flower development, leaf senescence and leaf surface wax characteristics. A
      diesel generator was used to produce concentrations of nitrogen oxides (NO(x))
      representative of urban conditions, in solardome chambers. Annual mean NO(x)
      concentrations ranged from 77 nl l(-l) to 98 nl l(-1), with NO:NO(2) ratios of
      1.4-2.2, providing a good experimental simulation of polluted roadside
      environments. Pollutant exposure resulted in species-specific changes in growth
      and phenology, with a consistent trend for accelerated senescence and delayed
      flowering. Leaf surface characteristics were also affected; contact angle
      measurements indicated changes in surface wax structure following pollutant
      exposure. The study demonstrated clearly the potential for realistic levels of
      vehicle exhaust pollution to have direct adverse effects on urban vegetation.

PMID- 19117656
TI  - Treatment of idiopathic retroperitoneal fibrosis with colchicine and steroids: a
      case series.
AB  - BACKGROUND: Idiopathic retroperitoneal fibrosis (IRPF) is an uncommon, but
      increasingly recognized, disease. Autoimmune mechanisms probably participate in
      its pathogenesis. Patients have been treated with high-dose steroids and
      sometimes immunosuppressive drugs, resulting in toxicity risk during prolonged
      treatments; thus, it would be wise to look for safer drugs. Colchicine has
      antifibrotic, anti-inflammatory, and immunosuppressive effects. Hence, it is a
      potential therapeutic resource. STUDY DESIGN: Case series. SETTING &
      PARTICIPANTS: 7 consecutives patients with IRPF diagnosed since 1993 at a navy
      hospital were prescribed colchicine plus prednisone or deflazacort. After
      reaching a clinical response, the steroid dose was tapered, maintaining daily
      colchicine therapy. OUTCOMES & MEASUREMENTS: Symptomatic improvement was defined
      as time to relief of symptoms; clinical improvement, time to normalization of
      inflammatory parameters with symptomatic improvement; radiological changes,
      percentage of decrease in retroperitoneal mass; recurrence, as the need to
      increase steroid dose or add immunosuppressors because of reactivation of
      inflammation; and treatment failure, as persistence of signs of active
      inflammation and/or decrease in retroperitoneal mass less than 50% and/or
      deterioration in kidney function at the last visit. RESULTS: At month 3 of
      treatment, all patients had symptomatic improvement and 67% had clinical
      improvement. Between 8 and 12 months, 67% of patients had a decrease in
      retroperitoneal mass greater than 50%. No recurrence or treatment failure was
      observed during follow-up (mean, 72.5 months). At the last visit, all patients
      had a significant decrease in retroperitoneal mass (mean, 79.8% +/- 19.7%). One
      patient died of septic shock on day 21 of treatment. LIMITATIONS: This series did
      not have a control group. CONCLUSIONS: Colchicine in association with a low
      induction dose of steroids (<0.5 mg/kg/d) produced remission rates in patients
      with IRPF similar to those for regimens using greater steroid doses alone or in
      combination with immunosuppressive drugs. In addition, colchicine may have
      contributed to recurrence prevention.

PMID- 19117657
TI  - Resuscitation of acute anthracycline-induced cardiogenic shock and refractory
      hypoxemia with mechanical circulatory supports: Pitfalls and strategies.

PMID- 19117658
TI  - Intraosseous infusion using the bone injection gun in the prehospital setting.

PMID- 19117659
TI  - Cognitive impairments in survivors of out-of-hospital cardiac arrest: a
      systematic review.
AB  - OBJECTIVE: To describe the current evidence on the frequency and nature of
      cognitive impairments in survivors of out-of-hospital cardiac arrest. DESIGN:
      Systematic review. DATA SOURCES: Pubmed, Embase, PsychInfo and Cinahl (1980
      2006). No language restriction was imposed. REVIEW METHODS: The following
      inclusion criteria were used: participants had to be survivors of out-of-hospital
      cardiac arrest, 18 years or older, and there had to be least one cognitive
      outcome measure with a follow-up of 3 months or more. Case reports and
      qualitative studies were excluded. The articles were screened on title, abstract
      and full text by two reviewers. All selected articles were reviewed and assessed
      by two reviewers independently using a quality criteria list. RESULTS: Out of the
      286 articles initially identified, 28 were selected for final evaluation. There
      was a high heterogeneity between the studies with regard to study design, number
      of participants, outcome measures and duration of follow-up. In general, the
      quality of the articles appeared low, with a few positive exceptions. The
      reported frequency of cognitive impairments in survivors of out-of-hospital
      cardiac arrest ranged from 6% to 100%. Memory problems were the most common
      cognitive impairment, followed by impairments in attention and executive
      functioning. Three high-quality prospective studies found that cognitive problems
      occurred in about half of the survivors of out-of-hospital cardiac arrest.
      CONCLUSION: There are few good studies on the frequency of cognitive impairments
      after out-of-hospital cardiac arrest. However, cognitive problems, in particular
      memory problems, seem common in survivors of out-of-hospital cardiac arrest.

PMID- 19117660
TI  - Multi-scale modelling of amyloid formation from unfolded proteins using a set of
      theory derived rate constants.
AB  - Traditional simulation and analysis of amyloid aggregation kinetics has involved
      the examination of a single lumped parameter taken to reflect the total mass of
      protein in amyloid form. However use of increasingly sophisticated multi
      experimental strategies capable of providing information on the structure of the
      growing fibril at the mesoscopic and atomistic level, has put extra information
      within the experimenter's reach. Although such data can be presented empirically,
      its incorporation into a theoretical model is more problematic due to scaling
      issues associated with modern day approaches which fall into either the particle
      based or statistical based categories. Here we present a coarse grained multi
      scale simulation of irreversible amyloid formation that straddles this simulation
      divide by using a set of theory derived size and conformation specific rate
      constants to simulate the kinetic evolution of the amyloid fibril population.
      This approach represents a potentially profitable simulation/analytical strategy
      that will help to probe more deeply into the underlying molecular driving forces
      behind the phenomenon of amyloid formation.

PMID- 19117661
TI  - Bisection of biotinylated soft spherical structures.
AB  - Biotin, a water soluble vitamin, upon conjugation with ditryptophan methyl ester
      affords soft spherical structures in the nanometer to micrometer range. The
      evolution of such morphology is ascribed to favorable interaction between biotin
      and tryptophan residues as suggested for high affinity biotin-avidin interaction.
      We report unprecedented observation that biotinylated soft spherical structures
      undergo bisection to reveal hemispherical capsule-like structures, in the
      presence of avidin. This study suggests singular approach of tuning bioinspired
      morphologies via natural principles of interaction and affinity. We envisage that
      such hemispherical capsules provide an expeditious entry into interesting soft
      structures which may be harnessed for potential applications.

PMID- 19117662
TI  - On the structure-based design of novel inhibitors of H5N1 influenza A virus
      neuraminidase (NA).
AB  - The structure-based design of novel H5N1 neuraminidase inhibitors is currently a
      research topic of vital importance owing to both a recent pandemic threat by the
      worldwide spread of H5N1 avian influenza and the high resistance of H5N1 virus to
      the most widely used commercial drug, oseltamivir-OTV (Tamiflu). A specific
      criterion used in this work for determining fully acceptable conformations of
      potential inhibitors is a previous experimental proposal of exploiting potential
      benefits for drug design offered by the '150-cavity' adjacent to the NA active
      site. Using the crystal structure of H5N1 NA (PDB ID: 2hty) as the starting
      point, in a set of 54 inhibitors previously proposed by modifying the side chains
      of oseltamivir, 4 inhibitors were identified using two different computational
      strategies (ArgusLab4.0.1, FlexX-E3.0.1) both to lower the binding free energy
      (BFE) of oseltamivir and to have partially acceptable conformations. These 4
      oseltamivr structure-based analogues were found to adopt the most promising
      conformations by identifying the guanidinium side chain of Arg156 as a
      prospective partner for making polar contacts, but none of the modified 4-amino
      groups of oseltamivir in the 4 favorable conformations was found to make polar
      contacts with the guanidinium side chain of Arg156. Hence, the structures of two
      additional inhibitors were designed and shown to further lower the binding free
      energy of OTV relative to the previous 54 inhibitors. These two novel structures
      clearly suggest that it may be possible for a new substituent to be developed by
      functional modifications at position of the 4-amino group of oseltamivir in order
      to make polar contacts with the guanidinium side chain of Arg156, and thereby
      enhance the binding of a more potent inhibitor. Several standpoints of vital
      importance for designing novel structures of potentially more effective H5N1 NA
      inhibitors are established.

PMID- 19117663
TI  - Improvement of fruit and vegetable waste anaerobic digestion performance and
      stability with co-substrates addition.
AB  - The effect of fish waste (FW), abattoir wastewater (AW) and waste activated
      sludge (WAS) addition as co-substrates on the fruit and vegetable waste (FVW)
      anaerobic digestion performance was investigated under mesophilic conditions
      using four anaerobic sequencing batch reactors (ASBR) with the aim of finding the
      better co-substrate for the enhanced performance of co-digestion. The reactors
      were operated at an organic loading rate of 2.46-2.51 g volatile solids (VS)l(
      1)d(-1), of which approximately 90% were from FVW, and a hydraulic retention time
      of 10 days. It was observed that AW and WAS additions with a ratio of 10% VS
      enhanced biogas yield by 51.5% and 43.8% and total volatile solids removal by 10%
      and 11.7%, respectively. However FW addition led to improvement of the process
      stability, as indicated by the low VFAs/Alkalinity ratio of 0.28, and permitted
      anaerobic digestion of FVW without chemical alkali addition. Despite a
      considerable decrease in the C/N ratio from 34.2 to 27.6, the addition of FW
      slightly improved the gas production yield (8.1%) compared to anaerobic digestion
      of FVW alone. A C/N ratio between 22 and 25 seemed to be better for anaerobic co
      digestion of FVW with its co-substrates. The most significant factor for enhanced
      FVW digestion performance was the improved organic nitrogen content provided by
      the additional wastes. Consequently, the occurrence of an imbalance between the
      different groups of anaerobic bacteria which may take place in unstable anaerobic
      digestion of FVW could be prevented.

PMID- 19117664
TI  - Laparoscopic radical prostatectomy as our bridge to the future?

PMID- 19117665
TI  - Reversible grasp reflexes in normal pressure hydrocephalus.
AB  - We present two cases of normal pressure hydrocephalus in combination with grasp
      reflexes. In both cases the grasp reflexes disappeared following high volume
      cerebrospinal fluid removal. In one of the cases the grasp reflexes returned over
      a period of weeks but again resolved following definitive cerebrospinal fluid
      shunting surgery, and remained absent until final follow up at 9 months. We
      hypothesise that resolving grasp reflexes following high volume CSF removal has
      both diagnostic and prognostic value in normal pressure hydrocephalus,
      encouraging larger studies on the relevance of primitive reflexes in NPH.

PMID- 19117666
TI  - Alterations in lipid peroxidation and antioxidant status in different types of
      intracranial tumors within their relative peritumoral tissues.
AB  - OBJECTIVES: Elevated levels of lipid peroxidation and changes in the
      concentration of enzymatic and non-enzymatic antioxidant systems have been
      reported in various cancers, but there are very few reports available of lipid
      peroxidation due to oxidative stress in patients with intracranial neoplasms. The
      purpose of this study was to assess alterations in lipid peroxidation and
      antioxidant status in different types of tumors and to compare the results with
      their relative peritumoral tissues and compare the oxidative status in different
      grades of tumors. PATIENTS AND METHODS: We investigated the extent of oxidative
      stress and the levels of antioxidants in 16 astrocytomas and 38 other different
      types intracranial tumors comparing the results with their corresponding
      peritumoral tissues and comparing the levels in between low-grade and high-grade
      tumors. The extent of lipid peroxidation as evidenced by the formation of
      thiobarbituric acid-reacting substances (TBARS), as well as the status of the
      antioxidant systems such as superoxide dismutase (SOD), glutathione reductase
      (GR) and reduced glutathione (GSH) in tumor tissues and adjacent peritumoral
      tissues was estimated. The tumoral tissues were also compared as to their degrees
      of malignancy. RESULTS: According to our results lipid peroxidation in brain
      tumor tissues was enhanced compared to the corresponding adjacent peritumoral
      tissues. This was accompanied by a significant tumoral decrease in both enzymatic
      and non-enzymatic antioxidants. The low levels of antioxidants in tumor tissues,
      might be related to an increased use of antioxidant systems to scavenge lipid
      peroxides. Also a striking elevation in TBARS levels, and decrease in SOD
      activity and GSH levels were seen in high-grade tumors when compared with low
      grades. CONCLUSION: These findings emphasize a consistent difference in the level
      of antioxidants between the tumoral sample and its corresponding peritumoral
      tissue, independently of the tumoral type, and the most pivotal action would seem
      to minimise exposure to endogenous and exogenous sources of oxidative stress.

PMID- 19117667
TI  - Atypical causes of nontraumatic intracranial subarachnoid hemorrhage.
AB  - BACKGROUND: To analyze the management and outcome of patients presenting with
      atypical causes of intracranial subarachnoid hemorrhage (SAH). METHODS: We
      performed a review of our last 820 nontraumatic-SAH patients and analyzed the
      management and outcome of patients where the SAH origin was not a ruptured
      aneurysm. The Glasgow Outcome Scale (GOS) was used to assess outcome 3 months
      after event. RESULTS: Thirty-two patients had atypical causes of SAH. In 15
      patients with Hunt and Hess (H&H) scores from 1 to 3 without focal neurological
      deficit (FND), 8 perimesencephalic non-aneurysmal SAH, 4 blood coagulation
      disorders, 1 sinus thrombosis, 1 vasculitis, and 1 unknown-origin-SAH (UOS) were
      diagnosed. Fourteen (93%) of these 15 patients were conservatively treated. In 17
      patients with H&H scores from 3 to 5 and FND, 8 tumors, 1 cavernoma, 1 sinus
      thrombosis, 1 arteriovenous malformation, 1 blood coagulation disorders, 2 UOS,
      and 3 dural fistulas were diagnosed. Fifteen (88%) of these 17 patients were
      interventionally treated. The neurological condition 3 months later was good (GOS
      4 and 5) in 12 of the 15 cases (80%) admitted with low-H&H scores, as well as in
      13 of the 17 cases (76%) admitted with high-H&H scores. Three patients died and
      four developed a severe disability. CONCLUSIONS: Patients presenting with
      atypical causes of SAH and high-H&H scores at admission are likely to harbor an
      intracranial organic process producing the bleeding. Despite this poor initial
      condition, their 3-month outcome can be similar to those of patients with low-H&H
      scores if the origin of the bleeding is properly treated.

PMID- 19117668
TI  - Early clinical and neuroradiological worsening after radiotherapy and concomitant
      temozolomide in patients with glioblastoma: tumour progression or radionecrosis?
AB  - OBJECTIVES: This study investigates the diagnosis and management of patients with
      resected brain glioblastomas who presented early clinical and neuroradiological
      worsening after the completion of the Stupp protocol. Its aim is to discuss the
      occurrence of early radionecrosis. METHODS: Fifty patients with brain
      glioblastoma treated by surgical resection and Stupp protocol were reviewed; 15
      among them (30%) had early clinical and neuroradiological worsening at the 6
      month follow-up. The MR spectroscopy and surgical findings of these patients are
      reviewed. RESULTS: MR spectroscopy was in favour of tumour recurrence in 14 among
      15 patients and showed radionecrosis in one. Among 10 patients who were
      reoperated on, 7 had histologically verified tumour recurrence or regrowth,
      whereas in 3 histopathology showed necrosis without evidence of tumour. The 7
      patients with tumour progression had prevalence of focal neuroradiological signs
      (6/7) and a survival of 7.5-12 months (median survival 10 months). The 4 patients
      with early radionecrosis (including one patient who was not reoperated on) had
      clinical worsening with mental deterioration, confusion and ataxia, and MR
      spectroscopy positive for tumour recurrence in 3. Three were alive 24-30 months
      after the end of the radiotherapy, whereas one died at 40 months. CONCLUSION:
      Early radionecrosis after the Stupp protocol is not a rare event due to the
      radiosensitization effect of temozolomide. This phenomenon may predict a durable
      response to radiotherapy. MR spectroscopy may simulate tumour recurrence. A
      correct diagnosis is necessary to avoid useless reoperations and incorrect
      withdrawal of temozolomide.

PMID- 19117669
TI  - Redox regulation in radiation-induced cytochrome c release from mitochondria of
      human lung carcinoma A549 cells.
AB  - Mitochondria in mammalian cells are well-known to play an important role in the
      intrinsic pathway of genotoxic-agent-induced apoptosis by releasing cytochrome c
      into cytosol and to be a major source of reactive oxygen species (ROS). The aim
      of this study was to examine whether mitochondrial ROS are involved in radiation
      induced apoptotic signaling in A549 cells. Post-irradiation treatment with N
      acetyl-L-cysteine (NAC) inhibited cytochrome c release from mitochondria but did
      not affect expression levels of Bcl-2, Bcl-X(L) and Bax, suggesting that late
      production of ROS triggered cytochrome c release. Experiments using DCFDA (a
      classical ROS fluorescence probe) and MitoAR (a novel mitochondrial ROS probe)
      demonstrated that intracellular and mitochondrial ROS were enhanced 6h after X
      irradiation. Furthermore, the O(2)(-*) production ability of mitochondria
      isolated from A549 cells was evaluated by ESR spectroscopy combined with a spin
      trapping reagent (CYPMPO). When isolated mitochondria were incubated with NADH,
      succinate and CYPMPO, an ESR spectrum due to CYPMPO-OOH was detected. This
      NADH/succinate-dependent O(2)(-*) production from mitochondria of irradiated
      cells was significantly increased in comparison with that of unirradiated cells.
      These results indicate that ionizing radiation enhances O(2)(-*) production from
      mitochondria to trigger cytochrome c release in A549 cells.

PMID- 19117670
TI  - Integrated treatment of landfill leachates including electrooxidation at pilot
      plant scale.
AB  - This paper reports the integration of advanced and conventional technologies to
      deal with the treatment of landfill leachates. The raw leachate, with average
      values of COD=4430 mg/L and N-NH(4)(+)=1225 mg/L, was first treated on site by an
      activated sludge large-scale process reducing the former parameters to 1750 mg/L
      (av.) of COD and 750 mg/L (av.) of N-NH(4)(+). Next, 50 L/h of the effluent were
      pumped to a pilot plant that included Fenton oxidation followed by an
      electrooxidation unit, provided with boron doped diamond anodes (anode area=1.05
      m(2)); almost complete removal of the organic matter and ammonium nitrogen was
      achieved. Comparison of the results with those obtained in the laboratory (70
      cm(2) of anode area) was performed observing a similar performance in the
      kinetics of COD removal, while differences were found in the ammonium removal
      rates. The specific energy consumption necessary to electro-oxidize the organic
      load below the disposal limit (COD<160 mg/L) at pilot plant scale was 35
      kWh/m(3).

PMID- 19117671
TI  - Peat filter performance under changing environmental conditions.
AB  - Peat is a candidate filter material for in situ treatment of urban runoff,
      contaminated groundwater and landfill leachates. Until now research has focused
      on peat sorption in batch experiments and there is a lack of knowledge on peat
      performance in filter beds. In this project column tests were carried out to
      evaluate the capacity of peat to remove As, Cd, Cu, Cr, Ni, Pb and Zn in multi
      metal solution under a range of environmental conditions that may be encountered
      in real-life applications (draining, water stagnation, freezing, change in pH and
      metal concentrations, input of NaCl and elevated DOC). The removal capacity was
      91-98% for Cd, Cu, Zn, Ni and Pb and the efficiency was unaffected by the changes
      of physical factors, but temporarily inhibited for solutions containing NaCl.
      Leaching of DOC from peat was detected in the initial samples and temporarily
      decreased metal removal. The peat filters showed high removal rates for Cd, Cu,
      Zn, Ni and Pb under all experimental conditions and are recommended for treatment
      of waters containing these elements. In contrast, peat was not found to be
      efficient for treatment of As and Cr in the multi-metal contaminated water at the
      pH range (6.7-8.0) studied.

PMID- 19117672
TI  - Solidified floating organic drop microextraction (SFODME) for simultaneous
      separation/preconcentration and determination of cobalt and nickel by graphite
      furnace atomic absorption spectrometry (GFAAS).
AB  - Solidified floating organic drop microextraction (SFODME), combined with graphite
      furnace atomic absorption spectrometry (GFAAS) was proposed for simultaneous
      separation/enrichment and determination of trace amounts of nickel and cobalt in
      surface waters and sea water. 1-(2-Pyridylazo)-2-naphthol (PAN) was used as
      chelating agent. The main parameters affecting the performance of SFODME, such as
      pH, concentration of PAN, extraction time, stirring rate, extraction temperature,
      sample volume and nature of the solvent were optimized. Under the optimum
      experimental conditions, a good relative standard deviation for six determination
      of 20 ng l(-1) of Co(II) and Ni(II) were 4.6 and 3.6%, respectively. An
      enrichment factor of 502 and 497 and detection limits of 0.4 and 0.3 ng l(-1) for
      cobalt and nickel were obtained, respectively. The procedure was applied to tap
      water, well water, river water and sea water, and accuracy was assessed through
      the analysis of certified reference water or recovery experiments.

PMID- 19117673
TI  - Treatment of anaerobic sludge digester effluents by the CANON process in an air
      pulsing SBR.
AB  - The CANON (Completely Autotrophic Nitrogen removal Over Nitrite) process was
      successfully developed in an air pulsing reactor type SBR fed with the
      supernatant from an anaerobic sludge digester and operated at moderately low
      temperatures (18-24 degrees C). The SBR was started up as a nitrifying reactor,
      lowering progressively the dissolved oxygen concentration until reaching partial
      nitrification. Afterwards, an inoculation with sludge containing Anammox biomass
      was carried out. Nitrogen volumetric removal rates of 0.25 g NL(-1)d(-1) due to
      Anammox activity were measured 35 d after inoculation even though the inoculum
      constituted only 8% (w/w) of the biomass present in the reactor and it was poorly
      enriched in Anammox bacteria. The maximal nitrogen removal rate was of 0.45 g NL(
      1)d(-1). By working at a dissolved oxygen concentration of 0.5 mg L(-1) in the
      bulk liquid, nitrogen removal percentages up to 85% were achieved. The reactor
      presented good biomass retention capacity allowing the accumulation of 4.5 g VSS
      L(-1). The biomass was composed by ammonia oxidizing bacteria (AOB) forming
      fluffy structures and granules with an average diameter of 1.6mm. These granules
      were composed by Anammox bacteria located in internal anoxic layers surrounded by
      an external aerobic layer where AOB were placed.

PMID- 19117674
TI  - Adsorption of Cr(VI) using silica-based adsorbent prepared by radiation-induced
      grafting.
AB  - Silica-based adsorbent was prepared by radiation-induced grafting of
      dimethylaminoethyl methacrylate (DMAEMA) onto the silanized silica followed by a
      protonation process. The FTIR spectra and XPS analysis proved that DMAEMA was
      grafted successfully onto the silica surface. The resultant adsorbent manifested
      a high ion exchange capacity (IEC) of ca. 1.30 mmol/g and the Cr(VI) adsorption
      behavior of the adsorbent was further investigated, revealing the recovery of
      Cr(VI) increased with the adsorbent feed and the equilibrium adsorption could be
      achieved within 40 min. The adsorption capacity, strongly depended on the pH of
      the solution, reached a maximum Cr(VI) uptake (ca. 68 mg/g) as the pH was in the
      range of 2.5-5.0. Furthermore, even in strong acidic (4.0 mol/L HNO(3)) or
      alkaline media (pH 11.0), the adsorbent had a sound Cr(VI) uptake capacity (ca.
      22 and 30 mg/g, respectively), and the adsorption followed Langmuir mode. The
      results indicated that this adsorbent, prepared via a convenient approach, is
      applicable for removing heavy-metal-ion pollutants (e.g. Cr(VI)) from waste
      waters.

PMID- 19117675
TI  - Diesel oil pool fire characteristic under natural ventilation conditions in
      tunnels with roof openings.
AB  - In order to research the fire characteristic under natural ventilation conditions
      in tunnels with roof openings, full-scale experiment of tunnel fire is designed
      and conducted. All the experimental data presented in this paper can be further
      applied for validation of numerical simulation models and reduced-scale
      experimental results. The physical model of tunnel with roof openings and the
      mathematical model of tunnel fire are presented in this paper. The tunnel fire
      under the same conditions as experiment is simulated using CFD software. From the
      results, it can be seen that most smoke is discharged directly off the tunnel
      through roof openings, so roof openings are favorable for exhausting smoke. But
      along with the decrease of smoke temperatures, some smoke may backflow and mix
      with the smoke-free layer below, which leads to fall in visibility and is
      unfavorable for personnel evacuation. So it is necessary to research more
      efficient ways for improving the smoke removal efficiency, such as early fire
      detection systems, adequate warning signs and setting tunnel cap.

PMID- 19117676
TI  - Structural modification of mordenite zeolite with Fe for the photo-degradation of
      EDTA.
AB  - Fe(2+) was incorporated inside mordenite through ion exchange technique in
      aqueous solution. The amount of Fe loading was 25-100 wt %, using FeSO(4).7H(2)O
      as precursor and Na-mordenite starting material Na-M. The Fe incorporated (Fe-M)
      thus prepared was characterized by XRD, FTIR and N(2) adsorption measurements. It
      was found that Fe mordenite retained the same structure as that for Na-mordenite
      which may indicate that Fe well dispersed into mordenite channels. BET indicated
      that Fe-M samples possessed higher surface area compared to the parent Na-M.
      Photocatalytic degradation of EDTA was carried out in presence of the prepared Fe
      M catalysts. Effects of catalyst concentration and temperature were also studied.
      Thermodynamic parameters calculated for 50% Fe-M showed the highest catalytic
      activity toward EDTA degradation.

PMID- 19117677
TI  - Extreme localization of electrons in space and time.
AB  - Electron emission from sharp metal tips can take place on sub-femtosecond time
      scales if the emission is driven by few cycle femtosecond laser pulses. Here we
      outline the experimental prerequisites in detail, discuss emission regimes and
      relate them to recent experiments in the gas phase (attosecond physics). We
      present a process that leads to single atom tip emitters that are stable under
      laser illumination and conclude with a discussion of how to achieve short
      electron pulses at a target.

PMID- 19117678
TI  - Correlation of the orientation of stacked aragonite platelets in nacre and their
      connection via mineral bridges.
AB  - In this work, we studied the correlation of the orientation of stacked aragonite
      platelets of Haliotis laevigata nacre, using selected area diffraction (SAD) in
      transmission electron microscopy (TEM). From the position of the center of Laue
      circle (COLC) within the diffraction patterns the tilt angles of the investigated
      platelets relatively to a reference platelet (oriented in zone axis) are
      determined. The strong correlation of the platelets supports the existence of
      mineral bridges, which connect the stacked platelets and enable a transfer of the
      platelet orientation during growth. Electron tomography and subsequent
      reconstruction of the obtained data yield information about the shape of the
      mineral bridges. The crystalline structure of the material within the mineral
      bridges was investigated by high resolution TEM (HRTEM).

PMID- 19117679
TI  - Identification of phases in gas-atomised droplets by combination of neutron and X
      ray diffraction techniques with atom probe tomography.
AB  - Powders of Al(68.5)Ni(31.5) alloy have been produced by gas atomisation and
      sieved in different grain size families. The resulting families have been
      analysed by combined neutron and X-ray diffraction in order to investigate the
      structure and identify the existing phases at the surface and in the bulk of the
      grains. The weight fraction of the identified phases (Al(3)Ni(2), Al(3)Ni and Al)
      has been estimated from a profile refinement with the FULLPROF computer codes. An
      additional phase was observed but could not be identified in the diffraction
      patterns. Starting from grains less than 5mum in diameter, samples have been
      shaped by annular focused ion beam into needles that were suitable for atom probe
      investigations. The structure and morphologies observed by different techniques
      are compared and discussed. It has also been possible to estimate the crystallite
      sizes and the strains corresponding to the different phases present in the
      powders from the refinement of the ND patterns. In addition to Al(3)Ni(2) and
      Al(3)Ni, a phase of composition close to the nominal one of the alloy was
      observed in the atom probe measurements. This phase could be one of the decagonal
      ones referred to in the literature. Small particles of composition close to
      Al(82)Ni(18) are attributed to the metastable Al(9)Ni(2) phase. The achieved
      conclusions demonstrate the complementarity of X-ray and neutron diffraction
      techniques and atom probe tomography to analyse complex structures.

PMID- 19117680
TI  - Prevalence of and risk factors associated with shedding of Cryptosporidium felis
      in domestic cats of Mississippi and Alabama.
AB  - The prevalence of and risk factors associated with the shedding of
      cryptosporidial oocysts were determined for domestic cats in northeastern
      Mississippi and northwestern Alabama. Cryptosporidial oocysts were found in a
      single fecal samples from 30 of 250 cats using a centrifugal concentration
      technique followed by an immunofluorescent assay. The odds of a cat shedding
      oocysts were increased when another cat shedding oocysts was present in the
      household. Logistic regression analysis showed only concurrent shedding of
      Giardia cysts to be significantly associated with the presence of Cryptosporidium
      oocysts in the feces. Oocysts from 12 cats were successfully genotyped, based on
      sequencing of a fragment of the 18S rRNA gene, all isolates were Cryptosporidium
      felis.

PMID- 19117681
TI  - Protective immunity of recombinant Mycobacterium bovis BCG expressing rhomboid
      gene against Eimeria tenella challenge.
AB  - Two recombinant Mycobacterium bovis BCG (rBCG) strains carrying the Eimeria
      tenella rhomboid gene (Rho) delivered by extrachromosomal vector pMV261 and
      integrative vector pMV361 were evaluated for their ability to protect chickens
      against E. tenella challenge. The chickens were immunized intranasal with BCG,
      rBCG pMV261-Rho, or rBCG pMV361-Rho twice at a 2-week interval. All the
      recombinant BCG immunized chickens developed specific immune responses, and there
      was a significant increases of the percentages of CD4(+) and CD8(+) cells
      compared to the control (P<0.05). Challenge experiments demonstrated that the two
      rBCG strains could provide significant protection against E. tenella challenge.
      But vaccination with rBCG pMV261-Rho induced higher specific antibody titers and
      produced greater protection rate (56.04%) than rBCG pMV361-Rho group (P<0.05).
      These results indicated that M. bovis BCG is a novel vaccine vector to express
      and present antigens of E. tenella, and rBCG has a potential as vaccine in
      chickens.

PMID- 19117682
TI  - Two new records of helminth parasites of domestic cat from Uruguay: Alaria alata
      (Goeze, 1782) (Digenea, Diplostomidae) and Lagochilascaris major Leiper, 1910
      (Nematoda, Ascarididae).
AB  - Eight helminth taxa were recovered from the necropsy of four stray domestic cats
      from Colonia Miguelete, county of Colonia, Uruguay. Two of them are recorded for
      the first time for domestic cats in that country: Alaria alata (Goeze, 1782) from
      the small intestine (which is also the first trematode species found in domestic
      cat in Uruguay), and Lagochilascaris major Leiper, 1910 from the pharynx. The
      remaining helminth species found were Toxocara mystax (Zeder, 1800) and
      Spirometra sp. from the small intestine, Trichuris serrata (von Linstow, 1879)
      from the caecum, Eucoleus aerophilus (Creplin, 1839) from the trachea, and
      Pearsonema feliscati (Diesing, 1851) from the urinary bladder. Moreover, four
      female specimens of an unidentified Spiruroidea were collected from the stomach
      and small intestine of one host.

PMID- 19117683
TI  - The immune response in Taenia solium neurocysticercosis in pigs is associated
      with astrogliosis, axonal degeneration and altered blood-brain barrier
      permeability.
AB  - Immunohistochemistry was used to examine the immuno-pathological changes and the
      extent of neuronal damage caused by either viable or dead Taenia solium
      cysticerci during porcine neurocysticercosis. Thirty pig brains with cerebral
      cysticercosis and 5 brains from T. solium free pigs were used in this study.
      Results revealed extensive astrogliosis, neuronal and mostly axonal damage in
      both early (grade I) and late (grades III and V) lesions as evidenced by an
      increased expression of glial fibrillary acidic protein (GFAP) and neurofilament
      protein (NFP). In many late lesions, astrocyte end-feet formed glial scars that
      surrounded the dead parasite. Rapid angiogenesis resulted in blood vessels
      lacking astrocyte end-feet suggesting loss of blood-brain barrier (BBB) hence
      allowing an influx of peripheral blood immune cells such as eosinophils,
      macrophages, CD3+ T cells, B lymphocytes and plasma cells into lesions. This
      study showed that porcine NCC was associated with severe nervous tissue damage,
      the host response of which is a collaborative effort between the local and
      peripheral immune responses comparable to that observed in human NCC. Results
      further implied that porcine NCC could be a useful model for understanding the
      course of NCC in human as well as provide useful information for therapeutic
      and/or immune strategies.

PMID- 19117684
TI  - Natural infection by Cryptosporidium sp., Giardia sp. and Eimeria leuckarti in
      three groups of equines with different handlings in Rio de Janeiro, Brazil.
AB  - To detect Cryptosporidium sp., Giardia sp. and Eimeria leuckarti in horses, fecal
      samples were collected from three different handling horse groups from the state
      of Rio de Janeiro, Brazil. Group A was composed of "Mangalarga Marchador" pure
      breed horses, Group B was formed by horses of a Military Corporation and Group C
      by stray horses captured by the Center of Zoonosis Control Paulo Dacorso Filho. A
      total of 396 fecal samples were collected, 212 samples from Group A, 154 samples
      from Group B and 30 from Group C. The material was submitted to the
      centrifugation - flotation technique and staining by the safranin-methylene blue
      technique and analyzed. Oocysts of Cryptosporidium sp. were identified in 0.75%
      of the samples (n=3); cysts of Giardia sp. in 0.5% (n=2) and oocysts of E.
      leuckarti in 0.5% (n=2). One case of E. leuckarti in group A and one of
      Cryptosporidium sp. in group B were observed. In group C were observed two cases
      of Cryptosporidium, two of Giardia and one of E. leuckarti,. Horses of group C
      were more parasitized by the three protozoans than animals from the other groups
      (p<0.01). It was possible to verify that factors related to the animals, like
      host individual susceptibility and sanitary factors may influence the occurrence
      of natural infections by gastrointestinal protozoans, although the age did not
      have influence. This study reports, for the first time, the occurrence of
      Cryptosporidium sp., Giardia sp. and E. leuckarti in equines of the State of Rio
      de Janeiro.

PMID- 19117685
TI  - TRAIL receptor signalling and modulation: Are we on the right TRAIL?
AB  - Tumour necrosis factor-related apoptosis-inducing ligand or Apo2 ligand
      (TRAIL/Apo2L) is a member of the tumour necrosis factor (TNF) superfamily of
      cytokines that induces apoptosis upon binding to its death domain-containing
      transmembrane receptors, death receptors 4 and 5 (DR4, DR5). Importantly, TRAIL
      preferentially induces apoptosis in cancer cells while exhibiting little or no
      toxicity in normal cells. To date, research has focused on the mechanism of
      apoptosis induced by TRAIL and the processes involved in the development of TRAIL
      resistance. TRAIL-resistant tumours can be re-sensitized to TRAIL by a
      combination of TRAIL with chemotherapeutics or irradiation. Studies suggest that
      in many cancer cells only one of the two death-inducing TRAIL receptors is
      functional. These findings as well as the aim to avoid decoy receptor-mediated
      neutralization of TRAIL led to the development of receptor-specific TRAIL
      variants and agonistic antibodies. These molecules are predicted to be more
      potent than native TRAIL in vivo and may be suitable for targeted treatment of
      particular tumours. This review focuses on the current status of TRAIL receptor
      targeting for cancer therapy, the apoptotic signalling pathway induced by TRAIL
      receptors, the prognostic implications of TRAIL receptor expression and
      modulation of TRAIL sensitivity of tumour cells by combination therapies. The
      mechanisms of TRAIL resistance and the potential measures that can be taken to
      overcome them are also addressed. Finally, the status of clinical trials of
      recombinant TRAIL and DR4-/DR5-specific agonistic antibodies as well as the pre
      clinical studies of receptor-selective TRAIL variants is discussed including the
      obstacles facing the use of these molecules as anti-cancer therapeutics.

PMID- 19117687
TI  - Clinical relevance of EGFR- and KRAS-status in colorectal cancer patients treated
      with monoclonal antibodies directed against the EGFR.
AB  - The epidermal growth factor receptor (EGFR) plays an important role in
      tumorigenesis and tumor progression of colorectal cancer (CRC). As a result, the
      EGFR has evolved as a relevant target in the treatment of metastatic CRC. KRAS
      serves as a mediator between extracellular ligand binding and intracellular
      transduction of signals from the EGFR to the nucleus. The presence of activating
      KRAS mutations has been identified as a potent predictor of resistance to EGFR
      directed antibodies such as cetuximab or panitumumab. These agents should
      therefore be applied only in tumors with a wild-type status of the KRAS gene.
      Further parameters of resistance are lack of EGFR amplification, PTEN loss or
      BRAF mutation. However, they are less well studied or associated with less
      consistent data and therefore require prospective analyses before integration
      into clinical decision making. Future studies need to identify patterns of single
      or multiple mutations to further increase the power of patient selection for anti
      EGFR therapy. While molecular parameters help to predict treatment efficacy
      upfront, skin toxicity has been accepted as an independent predictor of response
      during exposure to anti-EGFR therapy.

PMID- 19117686
TI  - Microtubule dynamics as a target in oncology.
AB  - Drugs that affect microtubule dynamics, including the taxanes and vinca
      alkaloids, have been a mainstay in the treatment of leukemias and solid tumors
      for decades. New, more effective microtubule-targeting agents continue to enter
      into clinical trials and some, including the epothilone ixapebilone, have been
      approved for use. In contrast, several other drugs of this class with promising
      preclinical data were later shown to be ineffective or intolerable in animal
      models or clinical trials. In this review, we discuss the molecular mechanisms as
      well as preclinical and clinical results for a variety of microtubule-targeting
      agents in various stages of development. We also offer a frank discussion of
      which microtubule-targeting agents are amenable to further development based on
      their availability, efficacy and toxic profile.

PMID- 19117688
TI  - The 3beta-hydroxysteroid dehydrogenase inhibitor trilostane shows antidepressant
      properties in mice.
AB  - Changes in neuro(active)steroid levels are involved in depressive states and mood
      disorders. For instance, dehydroepiandrosterone or pregnenolone sulfate showed
      anti-stress and antidepressant activity in rodents and regulation of
      allopregnanolone levels appeared to be one of the consequence of an effective
      antidepressant therapy in patients. 4alpha,5-Epoxy-17beta-hydroxy-3-oxo-5alpha
      androstane-2alpha-carbonitrile (trilostane) inhibits the activity of 3beta
      hydroxysteroid dehydrogenase (3beta-HSD) that, in particular, converts
      pregnenolone into progesterone. We examined whether systemic administration of
      trilostane affects the response to stress and depression. An acute treatment with
      trilostane (6.3-50mg/kg SC injected twice -16 and -2h before the measure)
      increased 3beta-HSD mRNA levels in the hippocampus and adrenals, but had little
      effect on protein levels. The trilostane treatment failed to affect open-field,
      locomotor or exploratory behaviors, but significantly reduced the immobility
      duration in the forced swimming test, measuring antidepressant-like activity, and
      increased the time spent in open arm in the elevated plus-maze, measuring anxiety
      response. The antidepressant-like effect of trilostane was effective after a
      repeated treatment (2.5-20mg/kgSC twice-a-day during 7 days) or in mice submitted
      to a restraint stress during 21 days and showing several behavioral and
      physiological parameters of depression (decreased body weight, increased adrenal
      glands weight and anhaedonia). Trilostane also reduced stress-induced increase in
      plasma corticosterone and ACTH levels, showing direct effect on HPA axis
      activity. These observations suggest that the 3beta-HSD inhibitor trilostane
      present antidepressant-like activity, putatively by regulating brain and
      peripheral levels of neuroactive steroids.

PMID- 19117689
TI  - Asymptomatic urinary abnormalities: histopathological analysis.
AB  - The aim of the study was to assess the characteristics of histopathological
      changes in 120 young males, both recruits and soldiers, who had undergone
      successful renal biopsy due to asymptomatic urinary abnormalities. The patients
      were subdivided into a group with isolated microhematuria (IMH-62 patients) and a
      group with asymptomatic microhematuria and proteinuria (MHP-58 patients). Light,
      immunofluorescence, and electron microscopy revealed that MHP was associated with
      more severe morphological changes, than IMH. The latter group included 6 subjects
      with normal biopsies and 13 subjects with minor abnormalities found only in two
      patients with MHP. The frequencies of particular nephropathies in the groups with
      IMH and MHP were as follows: 35% and 55% for IgA nephritis, 24% and 31% for non
      IgA mesangioproliferative glomerulonephritis (GN), 2% and 3% for focal
      proliferative GN, 3% and 3% for diffuse proliferative GN, 5% and 1% for thin
      basement membrane nephropathy, respectively. Rebiopsy, performed in eight
      patients due to worsening of proteinuria during the follow-up period, showed
      evidence of progression of morphological changes. Patients with IMH had
      significantly less prominent histopathological changes than patients with MHP.
      Therefore, renal biopsy cannot be recommended for patients with IMH unless
      specific indications are present.

PMID- 19117690
TI  - A Phase II study of synchronous three-dimensional conformal boost to the gross
      tumor volume for patients with unresectable Stage III non-small-cell lung cancer:
      results of Korean Radiation Oncology Group 0301 study.
AB  - PURPOSE: We evaluated the efficacy of synchronous three-dimensional (3D)
      conformal boost to the gross tumor volume (GTV) in concurrent chemoradiotherapy
      for patients with locally advanced non-small-cell lung cancer (NSCLC). METHODS
      AND MATERIALS: Eligibility included unresectable Stage III NSCLC with no pleural
      effusion, no supraclavicular nodal metastases, and Eastern Cooperative Oncology
      Group performance score of 0-1. Forty-nine patients with pathologically proven
      NSCLC were enrolled. Eighteen patients had Stage IIIA and 31 had Stage IIIB. By
      using 3D conformal radiotherapy (RT) techniques, a dose of 1.8 Gy was delivered
      to the planning target volume with a synchronous boost of 0.6 Gy to the GTV, with
      a total dose of 60 Gy to the GTV and 45 Gy to the planning target volume in 25
      fractions during 5 weeks. All patients received weekly chemotherapy consisting of
      paclitaxel and carboplatin during RT. RESULTS: With a median follow-up of 36.8
      months (range, 29.0-45.5 months) for surviving patients, median survival was 28.1
      months. One-, 2- and 3-year overall survival rates were 77%, 56.4%, and 43.8%,
      respectively. Corresponding local progression-free survival rates were 71.2%,
      53.7%, and 53.7%. Compliance was 90% for RT and 88% for chemotherapy. Acute
      esophagitis of Grade 2 or higher occurred in 29 patients. Two patients with T4
      lesions died of massive bleeding and hemoptysis during treatment (Grade 5).
      Overall late toxicity was acceptable. CONCLUSIONS: Based on the favorable outcome
      with acceptable toxicity, the acceleration scheme using 3D conformal GTV boost in
      this trial is warranted to compare with conventional fractionation in a Phase III
      trial.

PMID- 19117691
TI  - Pretreatment serum testosterone and androgen deprivation: effect on disease
      recurrence and overall survival in prostate cancer patients treated with
      brachytherapy.
AB  - PURPOSE: Low testosterone has been implicated as a possible adverse prognostic
      factor in patients with newly diagnosed prostate cancer. We evaluated the impact
      of pretreatment serum testosterone on survival after prostate brachytherapy.
      METHODS AND MATERIALS: From October 2001 to November 2004, 619 patients underwent
      brachytherapy and 546 had a pretreatment serum testosterone level measured.
      Pretreatment serum testosterone levels were assigned by the following criteria:
      below-normal (n = 105), low normal (n = 246), mid normal (n = 132), high normal
      (n = 50), and above normal (n = 13). Median follow-up was 5.2 years. Cause of
      death was determined for each deceased patient. RESULTS: Six-year biochemical
      progression-free survival (bPFS), cause-specific survival (CSS), and overall
      survival (OS) were 97.7%, 99.8%, and 89.2%. When comparing patients with low or
      low normal testosterone with those with average or higher testosterone, there was
      no significant difference in bPFS (97.6% vs. 98.4%; p = 0.72), CSS (99.8% vs.
      100%; p = 0.72), or OS (88.9% vs. 90.8%; p = 0.73). Among patients with average
      and higher pretreatment testosterone, there was no significant difference in
      outcomes when comparing patients who did and did not receive androgen deprivation
      therapy (ADT). For patients with low or low normal testosterone levels, there was
      no significant difference in bPFS or CSS when comparing patients who did and did
      not receive ADT. However, there was a trend toward lower OS in patients with
      baseline lower testosterone levels who also received ADT (83.9% vs. 91.3%, p =
      0.075). CONCLUSIONS: Low pretreatment testosterone levels alone did not affect
      disease recurrence or OS. Patients with baseline low testosterone who also were
      treated with ADT had a trend toward decreased OS.

PMID- 19117692
TI  - Long-term outcomes and toxicity of concurrent paclitaxel and radiotherapy for
      locally advanced head-and-neck cancer.
AB  - PURPOSE: To report the long-term outcomes and toxicity of a regimen of infusion
      paclitaxel delivered concurrently with radiotherapy in patients with locally
      advanced squamous cell carcinoma of the head and neck. PATIENTS AND METHODS:
      Between 1995 and 1999, 35 patients with nonmetastatic, Stage III or IV squamous
      cell carcinoma of the head and neck were treated with three cycles of paclitaxel
      as a 120-h continuous infusion beginning on Days 1, 21, and 42, concurrent with
      radiotherapy. The initial 16 patients received 105 mg/m(2)/cycle, and the
      subsequent 19 patients received 120 mg/m(2)/cycle. External beam radiotherapy was
      delivered to a dose of 70.2-72 Gy at five fractions weekly. Patients were
      followed to evaluate the disease outcomes and late toxicity of this regimen.
      RESULTS: The median follow-up for all patients was 56.5 months. The median
      survival was 56.5 months, and the median time to local recurrence was not
      reached. Of the 35 patients, 15 (43%) developed hypothyroidism. Of the 33
      patients who underwent percutaneous endoscopic gastrostomy tube placement, 11
      were percutaneous endoscopic gastrostomy tube dependent until death or their last
      follow-up visit. Also, 5 patients (14%) required a tracheostomy until death, and
      3 (9%) developed a severe esophageal stricture. All evaluated long-term survivors
      exhibited salivary hypofunction. Fibrosis in the radiation field occurred in 24
      patients (69%). CONCLUSION: The results of our study have shown that concurrent
      chemoradiotherapy with a 120-h infusion of paclitaxel provides long-term local
      control and survival in patients with squamous cell carcinoma of the head and
      neck. Xerostomia, hypothyroidism, esophageal and pharyngeal complications, and
      subcutaneous fibrosis were common long-term toxicities; however, the vast
      majority of toxicities were grade 1 or 2.

PMID- 19117693
TI  - Changes in excision cavity volume: prediction of the reduction in absolute volume
      during breast irradiation.
AB  - PURPOSE: The aim of this study was to determine the changes in the excision
      cavity volume due to the resolution of the surgical effects during the whole
      breast treatment. MATERIALS AND METHODS: Seventy-seven patients with early-stage
      (T1-2 N0) breast cancer treated with breast-conserving therapy were included for
      this study. All patients underwent a standard planning computed tomography (CT)
      scan before irradiation treatment. A second CT scan was performed in the week
      before the start of the boost. Excision cavity volumes were delineated based on
      the surgical clips and the (surrounding) seroma or hematoma or other surgical
      changes on both scans by an experienced physician. This resulted in the gross
      tumor volumes GTV1 and GTV2. RESULTS: The delineated volumes of the GTVs were on
      average 78.7 cm(3) (range, 1.1-236.0 cm(3)) and 29.7 cm(3) (range, 1.3-123.6
      cm(3)) for, respectively, GTV1 and GTV2. The time between the CT scans was on
      average 37 days (range, 29-74 days). This resulted in a reduction of on average
      62%. The absolute reduction per day of the GTV1 was -1.3 cm(3)/day (range, 0.3 to
      -5.4 cm(3)/day). A linear correlation (correlation coefficient r(2) = 0.81) was
      observed between the absolute volume of GTV1 and the absolute reduction per day.
      CONCLUSION: A significant reduction in excision cavity volume during whole breast
      irradiation was shown. The observed correlation might be helpful in the decision
      to perform a second CT scan to adapt the treatment plan.

PMID- 19117694
TI  - White matter fractional anisotropy correlates with speed of processing and motor
      speed in young childhood cancer survivors.
AB  - PURPOSE: To determine whether childhood medulloblastoma and acute lymphoblastic
      leukemia (ALL) survivors have decreased white matter fractional anisotropy (WMFA)
      and whether WMFA is related to the speed of processing and motor speed. METHODS
      AND MATERIALS: For this study, 17 patients (6 medulloblastoma, 5 ALL treated with
      high-dose methotrexate (MTX) (4 x 5 g/m(2)) and 6 with low-dose MTX (3 x 2
      g/m(2))) and 17 age-matched controls participated. On a 3.0-T magnetic resonance
      imaging (MRI) scanner, diffusion tensor imaging (DTI) was performed, and WMFA
      values were calculated, including specific regions of interest (ROIs), and
      correlated with the speed of processing and motor speed. RESULTS: Mean WMFA in
      the patient group, mean age 14 years (range 8.9 - 16.9), was decreased compared
      with the control group (p = 0.01), as well as WMFA in the right inferior fronto
      occipital fasciliculus (IFO) (p = 0.03) and in the genu of the corpus callosum
      (gCC) (p = 0.01). Based on neurocognitive results, significant positive
      correlations were present between processing speed and WMFA in the splenium (sCC)
      (r = 0.53, p = 0.03) and the body of the corpus callosum (bCC) (r = 0.52, p =
      0.03), whereas the right IFO WMFA was related to motor speed (r = 0.49, p <
      0.05). CONCLUSIONS: White matter tracts, using a 3.0-T MRI scanner, show
      impairment in childhood cancer survivors, medulloblastoma survivors, and also
      those treated with high doses of MTX. In particular, white matter tracts in the
      sCC, bCC and right IFO are positively correlated with speed of processing and
      motor speed.

PMID- 19117695
TI  - Fractionated stereotactic radiotherapy as reirradiation for locally recurrent
      head and neck cancer.
AB  - PURPOSE: We report early preliminary experience with CyberKnife radiosurgery (RS)
      as salvage treatment for locally recurrent head and neck cancer (HNC). METHODS
      AND MATERIALS: Between March 2004 and August 2006, 36 patients (44 sites) were
      treated with CyberKnife RS as reirradiation for locally recurrent HNC. Treatment
      sites were as follows: nasopharynx (8), maxillary sinus (8), neck lymph nodes
      (8), skull base (7), nasal cavity (4), retropharyngeal lymph nodes (3), orbit
      (2), and others (4). Total doses administered were 18-40 Gy (median, 30 Gy) in 3
      to 5 fractions to the 65%-85% isodose line for 3-5 consecutive days. Previous
      external radiation dose ranged from 39.6 to 134.4 Gy (median, 70.2 Gy). Gross
      tumor volume ranged from 0.2 to 114.9 cm(3) (median, 22.6 cm(3)). Median follow
      up was 17.3 months. RESULTS: Thirty-five of 44 sites were evaluated for response.
      Fifteen (42.9%) sites achieved complete response, 13 sites (37.1%) achieved a
      partial response, 3 (8.6%) sites maintained stable disease, and 4 sites (11.4%)
      showed tumor progression. Grade III acute complications were noted in 13
      patients. Late complications were observed in three patients (1 bone necrosis, 2
      soft tissue necrosis) during follow-up. CONCLUSION: These preliminary results
      suggest that fractionated stereotactic radiosurgery is an effective treatment
      modality as a salvage treatment with good short-term local control. The early
      overall response rate is encouraging. However, more experience and a longer
      follow-up are necessary to determine the role of fractionated stereotactic
      radiosurgery as a salvage treatment of locally recurrent HNC and to define long
      term complications.

PMID- 19117696
TI  - Elective clinical target volumes for conformal therapy in anorectal cancer: a
      radiation therapy oncology group consensus panel contouring atlas.
AB  - PURPOSE: To develop a Radiation Therapy Oncology Group (RTOG) atlas of the
      elective clinical target volume (CTV) definitions to be used for planning pelvic
      intensity-modulated radiotherapy (IMRT) for anal and rectal cancers. METHODS AND
      MATERIALS: The Gastrointestinal Committee of the RTOG established a task group
      (the nine physician co-authors) to develop this atlas. They responded to a
      questionnaire concerning three elective CTVs (CTVA: internal iliac, presacral,
      and perirectal nodal regions for both anal and rectal case planning; CTVB:
      external iliac nodal region for anal case planning and for selected rectal cases;
      CTVC: inguinal nodal region for anal case planning and for select rectal cases),
      and to outline these areas on individual computed tomographic images. The imaging
      files were shared via the Advanced Technology Consortium. A program developed by
      one of the co-authors (I.E.N.) used binomial maximum-likelihood estimates to
      generate a 95% group consensus contour. The computer-estimated consensus contours
      were then reviewed by the group and modified to provide a final contouring
      consensus atlas. RESULTS: The panel achieved consensus CTV definitions to be used
      as guidelines for the adjuvant therapy of rectal cancer and definitive therapy
      for anal cancer. The most important difference from similar atlases for
      gynecologic or genitourinary cancer is mesorectal coverage. Detailed target
      volume contouring guidelines and images are discussed. CONCLUSION: This report
      serves as a template for the definition of the elective CTVs to be used in IMRT
      planning for anal and rectal cancers, as part of prospective RTOG trials.

PMID- 19117697
TI  - Fractionated stereotactic radiotherapy treatment of cavernous sinus meningiomas:
      a study of 100 cases.
AB  - PURPOSE: We discuss our experiences with fractionated stereotactic radiotherapy
      (FSR) in the treatment of cavernous sinus meningiomas. METHODS AND MATERIALS:
      From 1995 to 2006, we monitored 100 patients diagnosed with cavernous sinus
      meningiomas; 84 female and 16 male patients were included. The mean patient age
      was 56 years. The most common symptoms were a reduction in visual acuity (57%),
      diplopia (50%), exophthalmy (30%), and trigeminal neuralgia (34%). Surgery was
      initially performed on 26 patients. All patients were treated with FSR. A total
      of 45 Gy was administered to the lesion, with 5 fractions of 1.8 Gy completed
      each week. Patient treatment was performed using a Varian Clinac linear
      accelerator used for cranial treatments and a micro-multileaf collimator.
      RESULTS: No side effects were reported. Mean follow-up period was 33 months, with
      20% of patients undergoing follow-up evaluation of more than 4 years later. The
      tumor control rate at 3 years was 94%. Three patients required microsurgical
      intervention because FSR proved ineffective. In terms of functional symptoms, an
      81% improvement was observed in patients suffering from exophthalmy, with 46% of
      these patients being restored to full health. A 52% improvement was observed in
      diplopia, together with a 67% improvement in visual acuity and a 50% improvement
      in type V neuropathy. CONCLUSIONS: FSR facilitates tumor control, either as an
      initial treatment option or in combination with microsurgery. In addition to
      being a safe procedure with few side effects, FSR offers the significant benefit
      of superior functional outcomes.

PMID- 19117698
TI  - The associations of binge alcohol use with HIV/STI risk and diagnosis among
      heterosexual African American men.
AB  - BACKGROUND: Studies on the mechanisms of the association between illicit drug use
      and HIV/STI provide important insight into why there are disproportionate rates
      of HIV/STI among heterosexual African American men; far less work has been
      conducted to examine the associations between binge alcohol use and HIV/STI risks
      in this population. OBJECTIVE: To assess whether binge alcohol use is associated
      with risky sexual behaviors and recent HIV/STI diagnosis among heterosexual
      African American men reporting multiple sex partners in the past year. METHODS:
      Participants (n=672) were heterosexually active African American men age 18-65
      years recruited from urban health centers and clinics in Boston, MA, and who
      participated in a health survey. Logistic regression analyses were used to assess
      associations between past 30 day binge drinking and the following outcome
      variables: unprotected sex, six or more sex partners in the past year, sex trade
      involvement, and past 6 month HIV/STI diagnosis. Analyses were adjusted to
      control demographics, incarceration history, illicit drug use, and injection drug
      use. RESULTS: Significant associations were observed between binge alcohol use
      and unprotected vaginal sex with non-main female partners (AOR=1.7, 95% CI=1.2
      2.3), unprotected anal sex with non-main female partners (AOR=2.3, 95% CI=1.4
      4.0), sex trade involvement (AOR=2.1, 95% CI=1.3-3.5), and recent HIV/STI
      diagnosis (AOR=1.9; 95% CI=1.05-3.6). CONCLUSION: Heterosexual African American
      men engaging in binge alcohol use may be at increased risk for HIV/STI; findings
      support the need for integrating alcohol risk reduction into HIV prevention
      programs targeting this population.

PMID- 19117699
TI  - Genetic diversity and correlation with feline infectious peritonitis of feline
      coronavirus type I and II: a 5-year study in Taiwan.
AB  - The outcomes of feline coronavirus (FCoV) infection vary greatly from
      asymptomatic or mild enteric infection to fatal feline infectious peritonitis
      (FIP). On the basis of in vitro neutralization tests, FCoVs can be divided into
      two serotypes. To explore the correlation between different types of FCoV and
      FIP, clinical specimens collected from 363 naturally infected cats during 2003
      2007 were analyzed. Amplification of a portion of the S gene from the FCoV was
      performed and a total of 222 cases were differentiated. Among them, 197 (88.7%)
      cats were type I-positive, 13 (5.9%) were type II-positive, and 12 (5.4%) were
      positive for both types. Irrespective of the predominance of type I FCoV
      infection in Taiwan, type II FCoV demonstrated a significantly higher correlation
      with FIP (p<0.01). Analysis of partial S gene sequences of the local type I and
      II FCoVs strains revealed that type I viruses were more genetically divergent
      (6.2-11.7%) than type II viruses (0.6-3.2%) within the 5-year study period. The
      higher genetic diversity of type I FCoVs might be due to the larger infected cat
      population and to the long period of viral persistence in asymptomatic cats in
      comparison to type II viruses.

PMID- 19117700
TI  - Identification of novel potential virulence-associated factors in Haemophilus
      parasuis.
AB  - Haemophilus (H.) parasuis is best known as the cause of Glasser's disease, a
      potentially fatal polyserositis in pigs. The mechanisms underlying virulence
      differences on the molecular level are largely unknown to date. We have compared
      the serotype 5 (causes polyserositis) and 11 (described as avirulent) reference
      strains by modified representational difference analysis, and identified five
      potentially virulence associated factors present in the invasive serotype 5
      strain, but not in the avirulent serotype 11 strain. Among these, a putative
      hemolysin operon, hhdBA, was identified, which is also present in half of the
      serotype reference strains described as virulent, but not in those reference
      strains that were reported to cause no disease in animal infection experiments.
      The presence of all identified genes was investigated in serotype reference
      strains as well as in 26 field isolates from clinically ill pigs. Determining the
      presence of these genes may be useful in H. parasuis diagnostics to judge a
      strain's potential to cause disease.

PMID- 19117701
TI  - Characterization of beta-hemolytic streptococci isolated from southern sea otters
      (Enhydra lutris nereis) stranded along the California coast.
AB  - The goal of this study was to characterize the beta-hemolytic streptococci
      cultured from southern sea otters (Enhydra lutris nereis) stranded off the coast
      of California (USA) and to verify identifications made using the Lancefield
      system. Lancefield serotyping and biochemical analysis alone was inadequate for
      isolate characterization. Final identification was based on sequence analysis of
      a portion of the 16s ribosomal RNA gene from 12 of the 35 total isolates. The
      majority of isolates (10 of 12; 83.3%) were Streptococcus phocae and reacted with
      Lancefield group G and F antisera or were less frequently untypeable. The
      remaining isolates belonging to Lancefield group G were identified as S.
      dysgalactiae subsp. equisimilis (2 of 12; 16.7%). This is the first report of S.
      phocae in southern sea otters and further evidence of S. phocae expressing cell
      surface antigens compatible with Lancefield group G typing.

PMID- 19117702
TI  - Identification of PDC-109-like protein(s) in buffalo seminal plasma.
AB  - The FN-2 family of seminal plasma proteins represents the major protein fraction
      of bovine seminal plasma. These proteins also constitute the major seminal plasma
      proteins fraction in horse, goat and bison seminal plasma and are present in pig,
      rat, mouse, hamster and human seminal plasma. BSP-A1 and BSP-A2, the predominant
      proteins of the FN-2 family, are collectively termed as PDC-109. Fn-2 proteins
      play an important role in fertilization, including sperm capacitation and
      formation of oviductal sperm reservoirs. Significantly, BSP proteins were also
      shown to have negative effects in the context of sperm storage. No conclusive
      evidence for the presence of buffalo seminal plasma protein(s) similar to PDC-109
      exists. Studies with buffalo seminal plasma indicated that isolation and
      identification of PDC-109-like protein(s) from buffalo seminal plasma by
      conventional methods might be difficult. Thus, antibodies raised against PDC-109
      isolated, and purified from cattle seminal plasma, were used for investigating
      the presence of PDC-109-like protein(s) in buffalo seminal plasma. Buffalo
      seminal plasma proteins were resolved on SDS-PAGE, blotted to nitro cellulose
      membranes and probed for the presence of PDC-109-like protein(s) using the PDC
      109 antisera raised in rabbits. A distinct immunoreactive band well below the 20
      kDa regions indicated the presence of PDC-109-like protein(s) in buffalo seminal
      plasma.

PMID- 19117703
TI  - Interrelationships among morphology, echotexture, and function of the bovine
      corpus luteum during the estrous cycle.
AB  - It has been suggested that ultrasound image attributes are a potential indicator
      of physiological and functional status of the corpus luteum (CL) in several
      species, including cattle. The aims of this study were to evaluate CL
      morphological, functional and echotextural characteristics, and also to
      investigate the hypothesis that those attributes are correlated and change
      similarly throughout an estrous cycle. Ovaries of crossbred (Bos taurus taurus x
      Bos taurus indicus) heifers were evaluated using ultrasonography daily throughout
      an interestrus interval using a B-mode, real-time ultrasound machine equipped
      with a 5 MHz linear-array rectal transducer, during a natural estrous cycle
      (Experiment 1; n=12) or during a shortened cycle, with luteolysis induction 10d
      after estrus (Experiment 2; n=6). Blood samples were collected for assay of
      plasma progesterone concentrations. Corpora lutea areas were measured and daily
      images of each CL were videotaped and digitized for computer-assisted analysis
      using custom-developed software. In Experiment 1, area of luteal tissue increased
      until a maximum value 10d after estrus (P<0.001), followed by a plateau phase,
      and then a decline beginning 14 d after estrus. Luteal tissue area was highly
      correlated to plasma progesterone concentrations (r=0.86; P<0.001). When
      luteolysis was induced in Experiment 2, loss of CL function (decrease in plasma
      progesterone concentrations to metestrous values) preceded tissue regression by
      48 h (24h compared with 72 h; P<0.001). The mean pixel value of ultrasound images
      did not change in Experiment 1 (P>0.70), but a day effect on this attribute was
      observed in Experiment 2 (P=0.052). In contrast, mean pixel value was correlated
      to plasma progesterone concentrations in Experiment 1 (r=-0.63; P<0.05), but not
      in Experiment 2 (r=-0.28; P>0.10). In regard to CL heterogeneity, defined as the
      standard deviation of the mean pixel value of the luteal tissue, a time effect
      was observed following both natural (Experiment 1; P<0.009) and luteolysis
      induced (Experiment 2; P<0.05) estrous cycles (P<0.05). Moreover, this variable
      was correlated with plasma progesterone concentrations (r=-0.71 and -0.58 in
      Experiments 1 and 2, respectively; P<0.01), indicating that CL images were more
      heterogeneous during metestrus and after luteolysis (functional regression). In
      summary, morphological and echotextural attributes were correlated with CL
      function and underwent similar changes during the estrous cycle. Luteal tissue
      heterogeneity, assessed by ultrasonography, is considered a potential indicator
      of CL functional status, because it is correlated to circulating progesterone
      concentrations.

PMID- 19117704
TI  - Cell cycle and apoptosis in normal and cloned bovine near-term placentae.
AB  - The bovine maternal epithelium is composed of cuboidal cells interspersed with
      low columnar cells having centrally located nuclei. Bovine trophoblast is
      composed of two cell types: mononuclear trophoblastic and giant trophoblastic
      cells that can have two or more nuclei. Number of apoptotic cells and
      proliferative cells are variable in both cell populations. This study compared
      tissue growth and apoptosis by flow cytometry in the cell population found at
      distinct placental regions (central region of placentomes, < or =1-cm
      microplacentomes and the interplacentomal region) between normal and cloned near
      term bovine pregnancies. After a morphological comparison between regions and
      groups (controls vs. clones), a lesser proportion of diploid to tetraploid cells
      was observed in the central region of placentomes and in microplacentomes from
      cloned-derived pregnancies. In addition, cloned animals had a fewer apoptotic
      cells in the central region of the placentome and in interplacentomal region and
      a greater proliferative capacity in all regions (cells in G(2)/M) near term as
      opposed to control animals. These results may reveal the existence of a
      relationship between such changes in the proportions of uterine and trophoblastic
      epithelial cells at the end of pregnancy and normal placental function. This
      could be related to faulty placentation in early pregnancy, placental
      insufficiency during pregnancy or lack of placental and/or fetal maturation in
      late pregnancy, which may contribute to some of the abnormalities after in vitro
      embryo manipulations, such as poor preparation and initiation of parturition,
      prolonged gestation and lesser post-natal survival in some cloned animals.

PMID- 19117705
TI  - An unusual case of suicide by sharp force.
AB  - A 43-year-old woman was found dead inside the bathtub in a sitting position with
      a knife embedded in chest. Multiple sharp force wounds were present: 4 stab
      wounds in the sternal region, 2 cut wounds in the neck, several longitudinal and
      transverse cuts in the arms. Scene circumstances and autopsy findings pointed
      toward a suicidal etiology. The case presented some particular aspects that
      allowed us to identify the mechanism of production of the lethal thoracic wound
      and to partially reconstruct the time-sequence of injuries.

PMID- 19117706
TI  - Postmortem blood concentrations of organophosphorus pesticides.
AB  - Cases involving acute fatalities due to ingestion of organophosphorus pesticides
      (OPs), such as chlorpyrifos, diazinon, malathion and parathion, are presented.
      Solid-phase extraction (SPE) and gas chromatography/mass spectrometry (GC/MS)
      were used for the analysis of OPs in postmortem blood. After extraction with an
      Oasis HLB cartridge, the eluent was evaporated to dryness under a nitrogen stream
      at 35 degrees C, reconstituted with ethanol, and then analyzed by GC/MS. Terbufos
      was used as an internal standard. Verification procedures, such as the limit of
      detection, limit of quantification, linearity of the calibration, precision and
      recovery were performed. Validation data were adequate for analyzing OPs in
      blood. Chlorpyrifos, diazinon, malathion and parathion were detected in 31
      postmortem blood samples. Parathion was the most frequently detected compound
      among the four pesticides. The mean concentrations of chlorpyrifos, diazinon,
      malathion and parathion were 0.72, 1.03, 0.82 and 2.90 mg/L, respectively.

PMID- 19117707
TI  - Age determination from central incisors of fetuses and infants.
AB  - Age at time of death for a fetus or infant is an important issue in the field of
      forensic science. Dental development can give an accurate measure of infant and
      fetal age and current literature does not include any studies of dental age from
      central incisor development. The objective of this study is to determine the age
      of deceased fetuses and infants by examining metric tooth development of central
      incisors in deceased fetuses and infants. Five dimensions of 76 maxillary and
      mandibular central incisors were measured: mesio-distal (MD), bucco-lingual (BL),
      crown height (CH), crown thickness (CT), and root height (RH). The results showed
      that 44.45+/-0-2 weeks is a sectional time for age calculations, which
      corresponds to 40 weeks from conception plus 4 to 5 weeks after birth. Four ATA
      entitled age formulas are derived to give the relation of age with tooth
      dimensions before and after 44.45 weeks [ATA is the special name given to the
      honor of the great Turkish leader Mustafa Kemal Ataturk (1881-1938)]. Age
      estimation can be calculated from these formulas with an accuracy of the age +/-0
      2 weeks. Also, calcification time can be determined from ATA formulas. In
      conclusion, the age of fetuses and infants can be assessed by the measurements of
      a single central incisor. According to this research, when estimating age during
      identification studies, forensic researchers must take into consideration the
      period of embryonic human growth and development.

PMID- 19117708
TI  - Case of three delayed complications of radiotherapy: bilateral vocal cord
      immobility, esophageal obstruction and ruptured pseudoaneurysm of carotid artery.
AB  - We report the first case of three delayed complications following irradiation for
      laryngeal carcinoma: bilateral vocal cord immobility, obstruction of esophagus
      and spontaneously ruptured pseudoaneurysm of common carotid artery. Medial
      fixation of bilateral vocal cords and stenosis of cervical esophagus were noted
      at 28 years after radiotherapy. Spontaneous rupture of a pseudoaneurysm bulging
      into the hypopharynx and obstruction of the esophagus occurred at 35 years after
      irradiation. The life-threatening hemorrhage was successfully treated by
      microcoil embolization of the common carotid artery. The relationship between
      these complications and irradiation is also discussed.

PMID- 19117709
TI  - Bilateral myoepithelioma of the nasopharynx: a case report.
AB  - Myoepithelioma is a rare salivary tumour which is usually encountered in the
      parotid gland. Outside the parotid, myoepithelioma may arise from minor salivary
      glands of the hard palate and less frequently in bronchi or breast. In this
      report we describe the unique case of a metachronous bilateral nasopharyngeal
      myoepithelioma arising from the tubaric regions. Its microscopic features,
      immunophenotype, and the differential diagnosis together with a review of
      literature are discussed.

PMID- 19117710
TI  - A simple method to monitor serum concentrations of fluoxetine and its major
      metabolite for pharmacokinetic studies.
AB  - A rapid, selective and sensitive isocratic reversed-phase HPLC assay coupled with
      MS/MS detection for simultaneous quantification of fluoxetine and its major
      active metabolite in serum samples has been developed. Analytes were extracted
      with a simple three step liquid-liquid procedure and chromatographic separation
      was achieved on a C18 column. Because of its sensitivity, this HPLC/MS/MS method
      is suitable both for routine therapeutic drug monitoring and for pharmacokinetic
      studies, due to its low limits of quantification.

PMID- 19117711
TI  - Liquid chromatography-electrospray ionization mass spectrometry determination of
      methylphenidate and ritalinic acid in conventional and non-conventional
      biological matrices.
AB  - A procedure based on liquid chromatography-electrospray ionization mass
      spectrometry is described for determination of methylphenidate (MPH) and its
      principal metabolite ritalinic acid (RA) in plasma, urine, oral fluid and sweat
      using 3,4-methylendioxypropylamphetamine (MDPA) as internal standard. Aliquots of
      100microL biological fluids and sweat patch were initially treated with
      acetonitrile, centrifuged, and clear supernatants evaporated and redissolved in
      10mM ammonium acetate. Chromatography was performed on a reversed-phase column
      using a gradient of 10mM ammonium acetate and acetonitrile as a mobile phase at a
      flow rate of 1mL/min. Separated analytes were confirmed and quantified by
      positive electrospray ionization mass spectrometry and selected ion monitoring
      acquisition mode. Limits of quantifications were 1ng/mL plasma, 1ng/sweat patch,
      0.5ng/mL oral fluid and urine for MHF; 1ng/mL plasma and oral fluid, 1ng/sweat
      patch, 0.5ng/mL urine for RA using 100microL biological fluids or one sweat-patch
      per assay. Calibration curves were linear over the calibration ranges for both
      MPH and RA, with r(2)>0.99. At three concentrations spanning the linear dynamic
      range of the assay, mean recoveries ranged between 67.9-90.3% for MPH and 36.3
      92.4% for RA in the different biological matrices. This method was applied to
      therapeutic monitoring of MHP and RA in conventional and non-conventional
      biological matrices from individuals in drug treatment.

PMID- 19117712
TI  - Artificial neural networks analysis used to evaluate the molecular interactions
      between selected drugs and human alpha1-acid glycoprotein.
AB  - Quantitative structure-retention relationships (QSRR) were proposed for alpha(1)
      acid glycoprotein (AGP) column using physicochemical molecular descriptors of the
      selected drugs and interacting with that column. The set of 52 structurally
      diverse drug compounds, with experimentally derived logarithms of retention
      factors (log k) values was considered. Thirty-six physicochemical property
      descriptors were calculated by standard molecular modeling and used to establish
      QSRR and predict the retention data by artificial neural network (ANN). The QSRR
      indicated that heat of formation (HF), Moriguchi n-octanol-water partition
      coefficient (M log P) and the energy of the highest occupied molecular orbital
      (HOMO) are the most important for interactions between drugs and AGP. The
      proposed ANN model based on selected molecular descriptors showed a high degree
      of correlation between log k observed and computed. The final model possessed a
      36-5-1 architecture and correlation coefficients for learning, validating and
      testing sets equaled 0.975, 0.950 and 0.972, respectively.

PMID- 19117713
TI  - Twelve years of coccidioidomycosis in Ceara State, Northeast Brazil:
      epidemiologic and diagnostic aspects.
AB  - Coccidioidomycosis is an endemic infection in the Americas caused by the
      dimorphic fungi Coccidioides immitis and Coccidioides posadasii. Although the
      disease occurs in Brazil in sporadic form, little information about these cases
      is available. In this study, we summarize the most important clinical,
      epidemiologic, and diagnostic features of coccidioidomycosis in Ceara State
      (Northeast Brazil) during the past 12 years. In this period, 19 cases of
      coccidioidomycosis were diagnosed. All the patients were young males and came
      from semiarid areas of the state. The majority of cases were associated to
      armadillo hunting, and pulmonary disease was the most common clinical
      presentation. In our laboratory, coccidioidomycosis was confirmed by culture,
      serology, and polymerase chain reaction tests, which together were very suitable
      for the diagnosis of this disease. Based on our local experience, we believe many
      cases of this disease are misdiagnosed or not diagnosed in our region. Therefore,
      some strategies for improvement of diagnosis should be encouraged by local
      authorities.

PMID- 19117714
TI  - A novel molecular pattern for methicillin-resistant Staphylococcus aureus in
      Milwaukee, WI clinical isolates.
AB  - Methicillin-resistant Staphylococcus aureus is a significant problem in
      healthcare settings around the world. To effectively track different strains, we
      used a number of genetic procedures. In this study, 252 clinical isolates from
      the Milwaukee, WI, area were analyzed by the multiplex polymerase chain reaction
      (PCR) method to determine which of the described types were present. Most strains
      were categorized into one of the known groups, although types III and IIIA
      strains were not found. An unusual variant was found in 17% of the samples. This
      variant (v1) contains an 800-base pair amplimer that was created from a unique
      configuration of 2 primers from different sets in the multiplex PCR procedure.
      Although superficially similar to a type I pattern, sequencing of the amplimer
      demonstrated that it is identical to a sequence from the USA300 strain, a type IV
      strain. It is suggested that this variant may have resulted from acquisition of
      an IS431 element near the dcs region. There is potential for misidentification of
      strains because of slight genetic alterations such as this one. Statistical
      analysis using a chi(2) contingency table demonstrated that
      amoxicillin/clavulanic acid resistance was significantly lower in types I and IA
      when compared with the other types, whereas erythromycin resistance was
      significantly lower in type I when compared with other types. However, there was
      not a significant difference for any of the new variants.

PMID- 19117715
TI  - Protein kinase C isoforms in the porcine corpus luteum: temporal and spatial
      expression patterns.
AB  - Porcine corpora lutea (CL) fail to show a luteolytic response to prostaglandin-F
      2alpha (PGF-2alpha) (ie, luteolytic sensitivity, or LS) until approximately day
      13 of the estrous cycle. In view of the importance of protein kinase C (PRKC) in
      PGF-2alpha signal transduction, it was hypothesized that limiting levels of 1 or
      more PRKC isoforms may explain the lack of LS before day 13. This hypothesis was
      tested by examining expression of mRNA and protein, and the cellular localization
      patterns of the 11 PRKC isoforms throughout the porcine estrous cycle, to
      determine whether PRKC expression correlates with and thus may be associated with
      the control of the acquisition of LS in the pig. The expression patterns show
      that for most PRKC isoforms (ie, PRKC alpha, beta 1, beta 2, delta, epsilon,
      theta, iota, and zeta), mRNA was maximally expressed on day 7 or day 10 (protein
      kinase D1 only) of the cycle, whereas PRKCs gamma, eta, and lambda were
      unchanged. At the protein level, only PRKC epsilon (PRKCE) significantly changed
      during the estrous cycle and was elevated on day 13 (versus days 4, 7, and 15;
      P<0.05). By immunofluoresence, most PRKC isoforms, including PRKCE, were
      localized to steroidogenic large luteal cells (LLC) and small (nonendothelial
      cell) luteal cell subtypes (SLC). In conclusion, since the increase in PRKCE
      protein expression (day 13) occurred coincidentally with the onset of LS (> or
      =day 12), these results support a potential role for PRKCE in control of the
      acquisition of LS in the pig.

PMID- 19117716
TI  - Surgical treatment of gastric cancer in Latvia: results of centralized
      experience.
AB  - BACKGROUND: Although the mortality for gastric cancer is decreasing in Western
      Europe and United States, it still remains high in Eastern Europe. This study was
      aimed at evaluating short- and long-term results of surgical treatment of gastric
      cancer performed in Latvia Oncology Center. METHODS: Retrospectively collected
      data from 461 patients who underwent gastrectomy with curative intent in Latvia
      Oncology Center from January 2001 to December 2005 were analyzed statistically.
      RESULTS: An average (range) of 92.2 (81-102) R0-R1 gastrectomies was performed
      each year. Post-operative complications occurred in 75 patients (16.3%); in
      hospital mortality was 3.3%. The overall 5-year survival was 50.8%. In 444 cases
      (96.3%) there was histopathologic confirmation of R0-resection with a 5-year
      survival of 52.5% (P<0.001). Considering pT category, 5-year survival was 88.6%
      for pT1 patients, 65% for pT2, 42.3% for pT3 and 27% for pT4 (P<0.001).
      Considering pN category, 5-year survival was 67% for pN0 patients, 30% for pN1
      and 29% for pN2-3 (P<0.001). CONCLUSIONS: Clinico-pathologic characteristics of
      patients who underwent resection with curative intent are comparable to other
      Western experiences. Short- as well as long-term results are also similar if not
      for pN+ patients where no difference between pN1 and pN2 cases was observed.

PMID- 19117717
TI  - [Bacterial infections in palliative care: antibiotics and therapeutic
      limitations].
AB  - The benefits of antibiotics treatments are not obvious at the end of life except
      for the symptomatic urinary infections. The numerous antibiotics prescribed raise
      economic and ecological problems in terms of bacterial resistances development
      and also in terms of quality of life. The control of symptoms has to be the main
      indication to prescribe antibiotics at the end of life. It is the general state,
      the prognostic of the patient, his wishes and those of his family, and his
      symptoms, controlled or not, that direct the decision to prescribe an antibiotic.
      Physicians must consider the objective of antibiotic treatment, the risk of side
      effects and the constraints related to this treatment before prescribing it for
      terminally ill people. They have to respect the bioethical principles, primarily
      the principles of beneficence, non-maleficience, and the respect to autonomy of
      the patient. In the event of decision of an antibiotic treatment at a patient at
      the end of the lifetime, the choice of this one must answer obviously the same
      requirements as in the other medical situations, within the framework of
      comprehensive and rigorous process.

PMID- 19117718
TI  - [Post-traumatic right diaphragmatic rupture].

PMID- 19117719
TI  - Relationships between memory inconsistency for traumatic events following 9/11
      and PTSD in disaster restoration workers.
AB  - The present study examined the relationships between memories for a single
      incident traumatic event - the 9/11 attack on the World Trade Center (WTC)--and
      posttraumatic stress disorder (PTSD). 2641 disaster restoration workers deployed
      at the WTC site in the aftermath of the attack were evaluated longitudinally, one
      year apart, for PTSD, using clinical interviews. Their recollection of the
      traumatic events was also assessed at these times. The results showed that recall
      of traumatic events amplified over time and that increased endorsement of traumas
      at Time 2 was associated with more severe PTSD symptoms. It was also shown that,
      of all the exposure variables targeted, memory of the perception of life threat
      and of seeing human remains were differentially associated with PTSD symptoms.
      Implications of the results are also discussed.

PMID- 19117720
TI  - Memory modification as an outcome variable in anxiety disorder treatment.
AB  - Learning and memory are interdependent processes. Memories are learned, and
      cumulative learning requires memory. It is generally accepted that learning
      contributes to psychopathology and consequently to pertinent memory formation.
      Neuroscience and psychological research have established that memory is an active
      reconstructive process that is influenced by thoughts, feelings, and behaviors
      including post-event information. Recent research on the treatment of anxiety
      disorders using medications (i.e., d-cyclcloserine) to alter neurological systems
      associated with memory used in conjunction with behavior therapy suggests that
      memory is part of a central mechanism in the etiology and maintenance of these
      conditions. The main thesis of this article is that learning-based interventions
      create new memories that may modify existing ones. This raises the possibility of
      using such memory modifications to measure intervention outcome. A connectionist
      context for understanding this phenomenon and informing intervention is provided,
      with specific reference to post-traumatic stress disorder, obsessive-compulsive
      disorder, and generalized anxiety disorder. Recommendations for future research
      examining the role of memory change in treatment outcome are suggested.

PMID- 19117721
TI  - The relation between public speaking anxiety and social anxiety: a review.
AB  - This article reviewed the literature on public speaking anxiety in the context of
      social phobia subtyping. In total, 18 empirical studies on subtype issues related
      to public speaking anxiety were analyzed. Results of the reviewed studies are
      discussed in relation to their research method, that is, whether it focused on
      qualitative or quantitative aspects of subtype differences and whether it used a
      clinical or community sample. Evidence supported the premise that public speaking
      anxiety is a distinct subtype, qualitatively and quantitatively different from
      other subtypes of social phobia. The significance of this finding for social
      phobia studies using speech tasks to assess participants' state anxiety and
      behavioral performance is discussed.

PMID- 19117722
TI  - Upgraded technology for contingent stimulation of mouth wiping by two persons
      with drooling and profound developmental disabilities.
AB  - Many persons with developmental and physical disabilities experience drooling
      (i.e., loss of saliva from the mouth). Technology was recently developed to help
      two of these persons reduce the negative effects of drooling by increasing mouth
      wiping responses. This study upgraded our initial approach and tested it with the
      two persons who we previously treated. Upgrading ensured that all technology
      components, including the stimulation sources, were on the participant's body and
      that stimulation for mouth wiping caused no (or limited) environmental
      disturbance. We also conducted a social validation assessment of the new
      technology and its effects, employing university students as social raters.
      Evidence showed that the participants used the upgraded technology successfully
      in settings attended by varieties of other persons. The university students
      involved in the social validation viewed the use of the technology as enjoyable,
      beneficial, and environmentally acceptable, and they largely supported it.

PMID- 19117723
TI  - Dynamic liquid association: complex learning without implausible guidance.
AB  - Simple associative networks have many desirable properties, but are fundamentally
      limited by their inability to accurately capture complex relationships. This
      paper presents a solution significantly extending the abilities of associative
      networks by using an untrained dynamic reservoir as an input filter. The
      untrained reservoir provides complex dynamic transformations, and temporal
      integration, and can be viewed as a complex non-linear feature detector from
      which the associative network can learn. Typically reservoir systems utilize
      trained single layer perceptrons to produce desired output responses. However
      given that both single layer perceptions and simple associative learning have the
      same computational limitations, i.e. linear separation, they should perform
      similarly in terms of pattern recognition ability. Further to this the extensive
      psychological properties of simple associative networks and the lack of explicit
      supervision required for associative learning motivates this extension overcoming
      previous limitations. Finally, we demonstrate the resulting model in a robotic
      embodiment, learning sensorimotor contingencies, and matching a variety of
      psychological data.

PMID- 19117724
TI  - Pseudo-pericardial tamponade after cardiac surgery.
AB  - Cardiac tamponade is a common cause of hypotension and low output after cardiac
      surgery. The authors present a case of false tamponade diagnosis on
      transesophageal echocardiography in a patient who underwent mitral valve
      replacement and coronary artery bypass grafting. The diagnosis was not confirmed
      at surgery, and the cause of the abnormal right atrial filling was a prominent
      Eustachian valve trapped in the suture for correction of an iatrogenic inferior
      vena cava laceration. Such a complication must be kept in mind when repairing
      inferior vena cava lacerations and should be more widely known.

PMID- 19117725
TI  - A new adaptive interpolation algorithm for 3D ultrasound imaging with speckle
      reduction and edge preservation.
AB  - Conventional interpolation algorithms for reconstructing freehand three
      dimensional (3D) ultrasound data always contain speckle noises and artifacts.
      This paper describes a new algorithm for reconstructing regular voxel arrays with
      reduced speckles and preserved edges. To study speckle statistics properties
      including mean and variance in sequential B-mode images in 3D space, experiments
      were conducted on an ultrasound resolution phantom and real human tissues. In the
      volume reconstruction, the homogeneity of the neighborhood for each voxel was
      evaluated according to the local variance/mean of neighboring pixels. If a voxel
      was locating in a homogeneous region, its neighboring pixels were averaged as the
      interpolation output. Otherwise, the size of the voxel neighborhood was
      contracted and the ratio was re-calculated. If its neighborhood was deemed as an
      inhomogeneous region, the voxel value was calculated using an adaptive Gaussian
      distance weighted method with respect to the local statistics. A novel method was
      proposed to reconstruct volume data set with economical usage of memory.
      Preliminary results obtained from the phantom and a subject's forearm
      demonstrated that the proposed algorithm was able to well suppress speckles and
      preserve edges in 3D images. We expect that this study can provide a useful
      imaging tool for clinical applications using 3D ultrasound.

PMID- 19117726
TI  - Familial disease, the HLA-DRB1 shared epitope and anti-CCP antibodies influence
      time at appearance of substantial joint damage in rheumatoid arthritis.
AB  - Rheumatoid arthritis (RA) progresses more rapidly in some patients than in others
      and diverse factors influence radiographic progression in a specific population.
      Thus, we searched for variables that are associated with an early appearance of
      substantial joint damage in patients with RA by using radiographic assessments. A
      cohort of 157 consecutively enrolled Colombian RA patients was followed for an
      average of 3.2+/-3.1 years. Information on patient demographics and cumulative
      clinical and laboratory manifestations over the course of the disease was
      registered, including family history of RA in first-degree relatives, extra
      articular manifestations, rheumatoid factor, anti-CCP3 antibodies, TNF single
      nucleotide polymorphism at -308 position, and HLA-DRB1 status. Radiographs were
      scored according to the Sharp-van der Heijde method. Survival analyses of the
      time at appearance of substantial joint damage were performed by using Weibull
      models. A review of literature about the influence of familial RA on the
      progression of disease was done. Our results show that family history of RA is
      consistently associated with joint damage (i.e. erosive and joint narrowing
      disease). This effect was not found in all the populations reviewed. In addition,
      we confirm the effect of HLA-DRB1 shared epitope and anti-CCP seropositivity on
      erosive disease. Family history of RA is a key risk factor for joint damage and
      depends on the investigated population because variations in both additive and
      non-additive genetic factors and the environmental variance are specific to the
      population. Our results emphasize the usefulness of assessing familial disease,
      testing anti-CCP antibodies and genotyping HLA-DRB1 gene in patients with RA
      because these factors may be used to predict clinical outcomes and guide
      therapeutic interventions.

PMID- 19117727
TI  - 360 degrees peri-implant, keratinised, soft-tissue grafting with
      stereolithographic-aided dressing plate.
AB  - Surgical procedures to improve the quality of peri-implant soft tissue are a
      routine part of dental implant practice, especially in the edentulous patient
      with a significant lack of attached keratinised tissue. The use of a dressing
      plate at the recipient site can be beneficial in supporting free, keratinised,
      soft-tissue grafts during the early healing phase, especially if grafting is
      undertaken around all aspects of the implant and not just to the facial section.
      This paper outlines the use of a dressing plate, constructed on a
      stereolithographic model, for use at second-stage implant surgery to allow for
      360 degrees peri-implant, keratinised, soft-tissue grafting.

PMID- 19117728
TI  - MMP-3 activation is a hallmark indicating an early change in TMJ disorders, and
      is related to nitration.
AB  - Recent studies on temporomandibular joint (TMJ) disorders have suggested that
      matrix metalloproteinases (MMPs) are closely involved in the pathophysiological
      progression of the internal derangement (ID) of TMJ. The aim of this study was to
      investigate MMPs in synovial fluid (SF) at different stages of ID. To examine the
      relationship between MMP activation and ID progression, 54 SF samples from ID
      patients were classified based on the criteria of Wilkes and were assayed for MMP
      activity. It was found that MMP-3 activity was transiently increased in the
      intermediate stage. This increase in the active form of MMP-3 was also confirmed
      by Western blotting. When the 54 samples were classified into two groups based on
      the presence or absence of inflammatory findings, the intensity of MMP-3 activity
      correlated with the inflammatory symptoms. These findings suggest that MMP-3
      activation is a hallmark of early degenerative changes in ID. The tylosin
      nitration by the peroxynitrite can regulate the enzyme activity. To elucidate the
      activating pathway of MMPs in vivo, nitrated proteins in SF were analysed by
      immunoprecipitation. Some nitrated proteins in SF were identified as MMP-2 and 
      3, and the nitration of MMP-3 rendered them active in vitro.

PMID- 19117730
TI  - Increased CCL1 levels in the sera and blister fluid of patients with bullous
      pemphigoid.

PMID- 19117731
TI  - Efficacy of teicoplanin for the prevention of surgical site infections after
      total hip or knee arthroplasty: a prospective, open-label study.
AB  - A prospective randomised study was conducted in three centres to evaluate the
      efficacy of teicoplanin as antimicrobial prophylaxis for arthroplasties. From a
      total of 616 patients undergoing total hip or knee arthroplasty, 278 patients
      operated on in one centre were administered a single dose of 10mg/kg teicoplanin
      upon introduction of anaesthesia and the remaining 338 patients operated on in
      the other two centres were administered multiple doses of comparators for 4-6
      days as decided by the attending physicians. Follow-up was done for 24 months. No
      differences were found between the two groups regarding gender, underlying
      diseases and duration of the operation. Surgical site infections (SSIs) were
      present in two patients in the teicoplanin arm (0.78%) and in 11 patients in the
      comparator arm (3.53%) (P=0.025 between groups). These were deep SSIs in four
      patients (two in each arm). Two cases of severe allergic reaction occurred, one
      in the teicoplanin arm and another in the comparator arm. It is concluded that
      single-dose teicoplanin was more effective as prophylaxis for total hip or knee
      arthroplasty compared with multiple doses of broad-spectrum antimicrobials.

PMID- 19117732
TI  - Regional cerebral blood flow patterns of change following the own body image
      exposure in eating disorders: a longitudinal study.
AB  - OBJECTIVE: The aim of the present study is to see if the changes in the regional
      cerebral blood flow (rCBF) experienced by restrictive anorexia nervosa (AR) and
      bulimia nervosa (BN) patients, following the exposure to their own body image,
      persist at follow-up. METHODS: Three single photon emission computed tomography
      (SPECT) were performed on nine patients with a DSM-IV diagnosis of AR, 13 with
      BP, and 12 controls: at rest, following a neutral stimulus, and after exposure to
      their previously filmed whole body image. Body dissatisfaction was measured by
      means of the Body Dissatisfaction Questionnaire (BSQ). One year later the same
      assessment was repeated. RESULTS: Following the exposure to their own body image,
      BN showed an increase in body dissatisfaction, which was associated with the
      increase in the rCBF of the Right Temporal Area. Those changes persisted at
      follow-up. DISCUSSION: More specific long term therapies are needed for the
      treatment of the averse response showed by ED patients to their own body image
      exposure that is associated with the hyperactivation of the right temporal area
      when they are confronted with their whole body image.

PMID- 19117733
TI  - Two-dimensional (43)Ca-(1)H correlation solid-state NMR spectroscopy.
AB  - Calcium-43 (nuclear spin, S=7/2) is an NMR insensitive low-gamma quadrupolar
      nucleus and up until recently only one-dimensional solid-state (43)Ca NMR spectra
      have been reported. Through-space correlation experiments are challenging between
      spin-12 and low-gamma quadrupolar nuclei because of the intrinsically weak
      dipolar interaction and the often-low natural abundance of the quadrupolar
      nucleus. Rotary-resonance recoupling (R(3)) has recently been used to re
      introduce hetero-nuclear dipolar interactions for sensitive high-gamma
      quadrupolar nuclei, but has not yet been applied in the case of low-gamma half
      integer quadrupolar nuclei. Here an effective and robust 2D (1)H-(43)Ca NMR
      correlation experiment combining the R(3) dipole-recoupling scheme with 2D HMQC
      is presented. It is demonstrated that the weak (43)Ca-(1)H dipolar coupling in
      hydroxyapatite and oxy-hydroxyapatite can be readily re-introduced and that this
      recoupling scheme is more efficient than conventional cross-polarization
      transfer. Moreover, three (43)Ca-(1)H dipolar coupled calcium environments are
      clearly resolved in the structurally unknown oxy-hydroxyapatite. This local
      information is not readily available from other techniques such as powder XRD and
      high resolution electron microscopy. R(3)-HMQC is also a desirable experiment
      because the set-up is simple and it can be applied using conventional multi
      resonance probes.

PMID- 19117734
TI  - Fabrication of the nanogapped gold nanoparticles film for direct electrical
      detection of DNA and EcoRI endonuclease.
AB  - In situ seeding growth of gold nanoparticles (AuNPs) by the reaction of HAuCl4
      and NH2OH has been employed in the fabrication of the nanogapped AuNPs film for
      direct electrical detection of DNA hybridization and DNA cleavage by EcoRI
      endonuclease. The distance between neighboring gold nanoparticles is less than
      the length of the probe DNA, implying that the DNA strand could bridge the AuNPs
      to provide an electron tunneling path between microelectrodes. The double
      stranded DNA (dsDNA) formed by hybridization of probe and target DNA is detected
      by current-voltage (I-V) curve measurements. When dsDNA is cleaved by restriction
      endonuclease EcoRI, the electron tunneling path can be cut off, which is
      reflected from the different slopes of I-V curves between dsDNA and dsDNA
      cleavage by EcoRI in the label-free electrical measurements. The novel and simple
      method of fabricating the nanogapped AuNPs film by in situ seeding growth could
      provide a promising bioanalytical platform for studying both DNA-DNA and DNA
      protein interactions.

PMID- 19117735
TI  - Diffusion of permanent liquid dye molecules in human hair investigated by
      positron lifetime spectroscopy.
AB  - The diffusion behavior of a commercial permanent liquid hair dye in human hair
      has been investigated using positron annihilation lifetime spectroscopy (PALS)
      and gravimetric sorption method. The positron technique makes it possible to non
      invasively characterize the angstrom sized free volume holes in hair, which are
      supposed to be express pathways for diffusion of small molecules. The o-Ps
      lifetime parameters tau3 and I3 decrease rapidly during the first 60 min of
      sorption time. The overall decrease in o-Ps lifetime (tau3) was well over 200 ps
      and o-Ps intensity (I3) drops by 3.5%. These positron results are explained in
      terms of dye molecules filling the free volume holes and hair morphology. The dye
      penetrates the cuticle rapidly, but slowly in cortex. The first hour of dyeing
      appears to be the most effective period of deposition of dye molecules within
      hair. These results are well corroborated by the sorption results which suggest
      that the dye diffusion is essentially a diffusion controlled (i.e. Fickian)
      process, with no observable relaxation effects. In the latter part of the
      sorption, where positron parameters remain almost constant, mass increase might
      be due to surface adhesion. These two stages of sorption are well separated by
      the positron technique. The sorption curve also yielded an average value of
      apparent diffusivity of the dye in hair. From this study, we conclude that the
      free volume theory and positron technique, widely used in polymer research, may
      expediently be used to understand hair properties, more importantly diffusion of
      dye molecules.

PMID- 19117736
TI  - Surface modification of PVDF porous membranes via poly(DOPA) coating and heparin
      immobilization.
AB  - Based on the strong adhesive behavior of poly(3,4-dihydroxy-l-phenylalanine) (or
      poly(DOPA)) on solid surface, poly(vinylidene fluoride) (PVDF) microporous
      membranes were surface-modified by the self-polymerization of DOPA in aqueous
      solution. Subsequently, heparin was immobilized covalently onto the obtained
      PVDF/poly(DOPA) composite membranes by the coupling between heparin and
      poly(DOPA) coating. The modified membranes were subjected to a long-term washing,
      and the firm immobilization of poly(DOPA) and heparin was confirmed by X-ray
      photoelectron spectroscopy (XPS). The results of water contact angle measurements
      showed that the hydrophilicity of PVDF membranes was significantly improved by
      the incorporation of poly(DOPA) and heparin. The effects of poly(DOPA) and
      heparin on membrane surface morphologies were also investigated by scanning
      electron microscopy (SEM).

PMID- 19117737
TI  - Effect of water vapor on the surface characteristics and cell compatibility of
      zein films.
AB  - In this study, zein microsphere films were fabricated via a solution casting
      method, and their surfaces were subsequently treated with a higher relative
      humidity. Changes in surface properties were characterized by contact-angle
      measurement and scanning electron microscopy (SEM). Human hepatoma cells (BEL
      7402) were used as model cells to evaluate cell adhesion, spreading and
      proliferation on zein films before and after treatment. Additionally, the
      adhesion and morphologies of rat platelets on zein films were also investigated
      to evaluate the blood compatibility of the films. The results showed that the
      hydrophilicity of zein films was changed after treatment, and the surface
      morphology varied, gradually becoming more smooth and the microspheres in the
      films disappeared. As the result, the adhesion and proliferation of BEL-7402
      cells were significantly improved, while HUVECs were more sensitive than BEL-7402
      cells to cell-substrate interactions. Adhesion of rat platelets could be
      inhibited on the treated zein films. The results suggest that the synergistic
      actions of hydrophilic properties and micro morphologies are responsible for the
      cell behaviors.

PMID- 19117738
TI  - [Active drug monitoring of adverse drug reactions in pediatric emergency
      department].
AB  - OBJECTIVES: The aim of this study was to systematically evaluate adverse drug
      reactions (ADRs) in children consulting at the pediatric emergency unit during a
      6-month period. METHOD: The regional pharmacovigilance center (CRPV) and the
      department of clinical pharmacology prospectively and systematically recorded all
      potential ADRs among patients younger than 18 years of age in the pediatric
      emergency unit reported at the daily staff meetings. All cases were then screened
      and validated by the CRPV. For validated cases, preventability, seriousness, and
      off-label use were evaluated. RESULTS: During the study period, from 1 March to 1
      September 2005, 90 children presented potential adverse drug events. ADRs were
      confirmed in 43 patients, 19 females and 24 males. Thirty-four patients (79%)
      were under the age of 5. According to the European definition, 14 patients (33%)
      had serious ADRs. One anaphylactic shock after amoxicillin injection;
      antimalarial prophylaxis misuse leading to convulsive status epilepticus,
      convulsion, and coma after hepatitis B and MMR vaccines were deemed life
      threatening. Three ADRs were considered avoidable. Antibiotics and vaccines were
      the most common possible cause of ADRs (76%). Skin reactions (n=27), fever (n=8),
      and gastric disorders (n=5) were the most common clinical manifestations.
      CONCLUSIONS: Because ADRs were reported by clinicians on a voluntary basis,
      serious ADRs were probably reported more systematically. Compared to a similar
      period without active monitoring, active drug monitoring of ADRs doubled the
      number of confirmed cases 43 vs 17, p<0.001. Close collaboration between the
      pharmacovigilance center, pharmacologists, and clinicians is necessary and seems
      feasible for improving the monitoring of ADRs in children.

PMID- 19117739
TI  - Using WordNet synonym substitution to enhance UMLS source integration.
AB  - OBJECTIVE: Synonym-substitution algorithms have been developed for the purpose of
      matching source vocabulary terms with existing Unified Medical Language System
      (UMLS) terms during the integration process. A drawback is the possible explosion
      in the number of newly generated (potential) synonyms, which can tax
      computational and expert review resources. Experiments are run using a synonym
      substitution approach based on WordNet to see how constraining two methodological
      parameters, namely, "maximum number of substitutions per term" and "maximum term
      length," affects performance. Our hypothesis is that these values can be
      constrained rather tightly--thus greatly speeding up the methodology--without a
      marked decline in the additional matches produced. Furthermore, we investigate
      whether a limitation on only the first of the two parameters is sufficient to
      achieve the same results. METHODS: A four-stage synonym-substitution methodology
      using WordNet is presented. A group of experiments is carried out in which the
      two methodological parameters "maximum number of substitutions per term" and
      "maximum term length" are varied. The purpose is to examine their effect on the
      growth in the number of potential synonyms generated and the associated loss of
      results. The experiments are based on the re-integration of the "Minimal Standard
      Terminology" (MST) into the UMLS. Synonym-substitution matches found to be
      inconsistent with the current content of the UMLS and thus deemed to be incorrect
      are further manually scrutinized as an audit of the original integration of the
      MST. RESULTS: An increase of 11% in the number of "MST term/UMLS term" matches
      was achieved using the synonym-substitution methodology. Importantly, this result
      prevailed when tight threshold values (such as a maximum of two synonym
      substitutions per term) were imposed on the parameters. Furthermore, it was found
      that limiting only the "maximum number of substitutions per term" parameter was
      sufficient to obtain the performance enhancement. During the additional audit
      phase, a number of the reported mismatches were actually seen to be correct,
      representing an additional 10% increase in the number of matches obtained.
      CONCLUSION: A synonym-substitution methodology that utilizes WordNet is a useful
      automated aide in UMLS source integration. Experiments showed that there was a
      significant speed-up but no degradation in match results when the methodology's
      "maximum number of substitutions per term" parameter was relatively tightly
      constrained. The methodology also helped to discover errors in the MST's original
      integration, and improve the quality of the UMLS's conceptual content.

PMID- 19117740
TI  - Bronchial and peripheral airway nitric oxide in primary ciliary dyskinesia and
      bronchiectasis.
AB  - Primary ciliary dyskinesia (PCD) is a genetic condition resulting in
      bronchiectasis. Exhaled gas nitric oxide (FE(NO)) is reduced in PCD. A model of
      pulmonary NO exchange dynamics can be used to demonstrate relative contributions
      of bronchial (J'aw(NO)) and peripheral airway (Calv(NO)) NO to the final FE(NO)
      concentration. The aim of this study was to compare bronchial and peripheral
      airway contribution to FE(NO) in patients with PCD, non-PCD bronchiectasis and
      healthy controls in order to establish the source of present FE(NO) in these
      conditions and to compare these with severity of disease. NO was measured at 50,
      100, and 200 ml/s using an NO analyser (NiOx Sweden). J'aw(NO) and Calv(NO) were
      calculated according to a model of pulmonary exchange dynamics. PCD patients had
      reduced levels of J'aw(NO) compared to healthy controls whereas patients with non
      PCD bronchiectasis had elevated J'aw(NO) levels. There was no difference in
      Calv(NO) between the three groups. In the disease groups Calv(NO) correlated
      negatively with FEV(1). In conclusion patients with PCD had significantly reduced
      FE(NO) at all expiratory flow rates. This was due to a significantly low
      bronchial NO. In contrast, peripheral airway NO was increased with more severe
      disease.

PMID- 19117741
TI  - Impact of graft colonization with gram-negative bacteria after lung
      transplantation on the development of bronchiolitis obliterans syndrome in
      recipients with cystic fibrosis.
AB  - Bronchiolitis obliterans syndrome (BOS) represents the leading cause of late
      mortality after lung transplantation (LTx). Cystic fibrosis (CF) patients
      frequently show airway colonization with gram-negative bacteria (GNB) both before
      and after LTx. Graft colonization with GNB and its relevance towards BOS
      development were investigated in a CF population after LTx. Adult CF patients
      receiving LTx and surviving at least 6 months were included in this prospective
      observational study between 1/1/2002 and 30/6/2006 in a single center and
      followed until 31/3/2007. Pre- and post-LTx respiratory culture samples were
      compared for the presence of identical GNB. BOS-free survival was compared in
      colonized and non-colonized patients. Fifty-nine adult CF patients with a median
      age at LTx of 25.5 (18-49) years were included and had a median follow-up of 966
      (128-1889) days. Seven patients (15%) demonstrated immediate eradication of GNB
      in lower respiratory tract samples. A further 18 patients (34%) demonstrated
      transient colonization. Thirty-four recipients had further positive samples after
      LTx. Eighteen patients (31%) developed BOS >or=stage 1, 508 (114-1167) days after
      LTx. Freedom of graft colonization with pseudomonads was independently associated
      with less frequent development of BOS (p=0.006). Persistent graft colonization
      with pseudomonads increases the prevalence of BOS after LTx in CF patients. A
      significant proportion of post-LTx CF patients demonstrates subsequent GNB
      eradication during later follow-up and this may have a protective role against
      development of BOS. Strategies to eradicate airway colonization or reduce
      bacterial load may prevent BOS in CF patients after LTx.

PMID- 19117742
TI  - Pregnancy experiences among women with lymphangioleiomyomatosis.
AB  - Lymphangioleiomyomatosis (LAM) is a rare lung disease affecting women. Following
      case reports that pregnancy exacerbates LAM, patients are frequently advised to
      avoid pregnancy. Our objective was to determine pregnancy and health outcomes in
      LAM to provide better evidence with which to council patients contemplating
      pregnancy. We surveyed 328 women with LAM regarding pregnancy outcomes, pulmonary
      function, subjective and psychological functioning, quality of life, dyspnoea and
      fatigue. Amongst childless women the main reason not to attempt pregnancy was
      based on concerns about potential effects of pregnancy on LAM. Almost two thirds
      of patients had been pregnant, the majority before LAM was diagnosed, in whom
      pregnancy outcome was generally favourable. Women diagnosed with LAM (n=15)
      during pregnancy had high rates of pneumothorax (67%), miscarriage (7%) and
      premature birth (47%). The group diagnosed with LAM before or during pregnancy
      (n=12) had lower mean FEV(1), FVC and DLCO after pregnancy compared with those
      diagnosed following pregnancy or never pregnant. There were no differences in
      subjective or psychological functioning, quality of life, dyspnoea or fatigue
      scores between groups. In newly diagnosed LAM patients there was a high incidence
      of premature birth and pneumothorax. These adverse outcomes may be a marker of
      aggressive LAM.

PMID- 19117743
TI  - A comparison of four algorithms for the measurement of interrupter respiratory
      resistance in adults.
AB  - The aim of our study was to compare four algorithms for the measurement of
      respiratory resistance in adults using the interrupter technique. Four methods to
      estimate alveolar pressure from the mouth pressure during occlusion were assessed
      in 122 normal adults (57 males, 65 females, aged 18-79 yr, mean 41.2 +/- 15.6):
      taking the mean oscillation pressure (Rint), performing a linear back
      extrapolation (RintL) or a linear regression for the whole curve (RintRL), taking
      the end-occlusion pressure (RintE). Mean values for Rint, RintL and RintRL in
      males were respectively 0.23 +/- 0.04, 0.22 +/- 0.04 and 0.22 +/- 0.04 kPa s L(
      1), not statistically different. In females values were respectively 0.27 +/-
      0.05, 0.26 +/- 0.05 and 0.26 +/- 0.05 kPa s L(-1), not statistically different.
      RintE was higher than the remainder and was the only measure correlating weakly
      with morphometric variables: RintE = 1.152 - (0.00152 x age (yr)) - (0.00382 x
      height (cm)), r = 0.31 (p < 0.05) in females; RintE = 0.227 - (0.00122 x age
      (yr)) + (0.00830 x body mass index (kg m(-2))) with r = 0.34 (p < 0.05) in males.
      We conclude that it is equivalent to estimate alveolar pressure from or
      extrapolating it to the beginning of occlusion in healthy adults but when taking
      the end-occlusion pressure, resistance is higher and depends in part on
      morphometric parameters.

PMID- 19117744
TI  - Duration of pulmonary rehabilitation to achieve a plateau in quality of life and
      walk test in COPD.
AB  - OBJECTIVE: To address the minimum duration of pulmonary rehabilitation necessary
      for patients with chronic obstructive pulmonary disease (COPD) to achieve a
      plateau in Health-Related Quality of Life (HRQL) and exercise tolerance. METHODS:
      COPD patients with a dyspnea rating of at least 2 on the Medical Research Council
      scale participated in an outpatient rehabilitation program of 3 weekly sessions
      for 12 weeks. Measurements included HRQL and exercise tolerance 2 weeks before
      the program started and every 2 weeks thereafter. Patients were considered to
      have reached a plateau if they showed no improvement beyond 20% of the minimal
      important difference between 2 consecutive evaluations on HRQL score or walk
      tests. RESULTS: Twenty-eight patients participated. The number of patients
      achieving stability after 8 weeks, showing continued improvement after 8 weeks,
      and demonstrating an erratic pattern of change was as follows: for physical
      function 16 (56%), 10 (37%) and 2 (7%) patients; for emotional function 22 (79%),
      5 (18%) and 1 (4%); and for 6-min walk test 21 (75%), 5 (18%) and 2 (7%). More
      severe patients demonstrated a greater likelihood (76%) of achieving stability in
      physical function at 12 weeks than did less severe patients (27%; p on
      difference=0.003). The likelihood of stability at 12 weeks in emotional function
      and the 6-min walk test did not differ by severity. CONCLUSIONS: A program of 3
      weekly 3-h sessions of outpatient pulmonary rehabilitation program should last at
      least 8 weeks in order to achieve optimal HRQL and exercise tolerance for most
      patients.

PMID- 19117745
TI  - Cytokine gene polymorphisms and BALF cytokine levels in interstitial lung
      diseases.
AB  - BACKGROUND: The aim of our study is to investigate correlations of T(H)1/T(H)2
      cytokine gene polymorphisms and bronchoalveolar lavage fluid (BALF) cytokine
      values in interstitial lung diseases (ILD). METHODS: In 16 sarcoidosis, 7
      idiopathic pulmonary fibrosis (IPF) and 8 hypersensitivity pneumonitis (HP)
      patients we evaluated IL-1 alpha, -1R, -1RA, -2, -4, -4R alpha, -6, -10, -12, IFN
      gamma, TGF-beta1 and TNF-alpha gene polymorphisms in peripheral blood, and MCP
      1,MIP-1 alpha, MIP-1 beta, RANTES, ENA-78, FGF, G-CSF, GM-CSF, IFN-gamma, IL-1
      alpha, IL-1RA, IL-1 beta, -2, -4, -5, -6, -8, -10, -17, TNF-alpha, Tpo and VEGF
      values in BALF. RESULTS: We found higher TNF-alpha values in IL-1R pst 1970 TT
      homozygotes regardless of diagnosis (p=0.0126). In the sarcoidosis group IL-4R
      alpha(+1902)AA and IL-10(-1082)G allele correlated with higher BALF ENA-78 levels
      (p=0.0258, p=0.0230). In the HP group the IL-6(-174)CG and IL-6(nt565)AG
      correlated with higher ENA-78 BALF levels (p=0.0253). In the IPF group the IL-1
      beta +3962 CC homozygotes had lower IL-1RA BALF values (p=0.046). BALF chemokine
      values did not differ between ILD subgroups, except for IL-8, which was higher in
      stage III sarcoidosis patients compared to stage I. CONCLUSION: Our results show
      a probable influence of gene polymorphisms, namely IL-4R alpha and IL-10 on ENA
      78 BALF levels in sarcoidosis, IL-6 on ENA-78 BALF levels in HP and IL-1-beta on
      IL-1RA BALF values in the IPF group. The TNF-alpha BALF values correlated with IL
      1R pst 1970 gene polymorphisms.

PMID- 19117746
TI  - A statistical analysis to assess the maturity and stability of six composts.
AB  - Despite the long-time application of organic waste derived composts to crops,
      there is still no universally accepted index to assess compost maturity and
      stability. The research presented in this article investigated the suitability of
      seven types of seeds for use in germination bioassays to assess the maturity and
      phytotoxicity of six composts. The composts used in the study were derived from
      cow manure, sea weeds, olive pulp, poultry manure and municipal solid waste. The
      seeds used in the germination bioassays were radish, pepper, spinach, tomato,
      cress, cucumber and lettuce. Data were analyzed with an analysis of variance at
      two levels and with pair-wise comparisons. The analysis revealed that composts
      rendered as phytotoxic to one type of seed could enhance the growth of another
      type of seed. Therefore, germination indices, which ranged from 0% to 262%, were
      highly dependent on the type of seed used in the germination bioassay. The
      poultry manure compost was highly phytotoxic to all seeds. At the 99% confidence
      level, the type of seed and the interaction between the seeds and the composts
      were found to significantly affect germination. In addition, the stability of
      composts was assessed by their microbial respiration, which ranged from
      approximately 4 to 16g O(2)/kg organic matter and from 2.6 to approximately 11g
      CO(2)-C/kg C, after seven days. Initial average oxygen uptake rates were all less
      than approximately 0.35g O(2)/kg organic matter/h for all six composts. A high
      statistically significant correlation coefficient was calculated between the
      cumulative carbon dioxide production, over a 7-day period, and the radish seed
      germination index. It appears that a germination bioassay with radish can be a
      valid test to assess both compost stability and compost phytotoxicity.

PMID- 19117747
TI  - Ultrasensitive detection of testosterone using conjugate linker technology in a
      nanoparticle-enhanced surface plasmon resonance biosensor.
AB  - A rationally designed oligoethylene glycol linker conjugate to testosterone was
      synthesised and covalently immobilized on a surface plasmon resonance (SPR)
      biosensor surface. The sensing surface was stable for more than 330 binding and
      regeneration cycles allowing a high degree of re-use. This surface was then used
      in the development of an ultrasensitive immunobiosensor system for testosterone
      in buffer utilizing both secondary antibody and gold nanoparticle signal
      enhancement. The mechanism for the increased sensitivity results from increased
      binding mass and a gold plasmon coupling effect. The addition of a secondary
      antibody with an attached gold nanoparticle increased the signal sensitivity of
      the assay 12.5-fold compared with primary antibody alone. In the enhanced format
      the assay had limits of detection (LOD) of 3.7 pgml(-1) with standard in running
      buffer, and 15.4 pgml(-1) in a stripped human saliva matrix. This immunobiosensor
      system has sufficient sensitivity to measure testosterone across the broad
      physiologically relevant range in male saliva (29-290 pgml(-1)) in under 13 min
      allowing monitoring of testosterone in near real-time.

PMID- 19117748
TI  - Aptasensors for detection of microbial and viral pathogens.
AB  - Aptamers are specific nucleic acid sequences that can bind to a wide range of non
      nucleic acid targets with high affinity and specificity. These molecules are
      identified and selected through an in vitro process called SELEX (systematic
      evolution of ligands by exponential enrichment). Proteins are the most common
      targets in aptamer selection. In diagnostic and detection assays, aptamers
      represent an alternative to antibodies as recognition agents. Cellular detection
      is a promising area in aptamer research. One of its principal advantages is the
      ability to target and specifically differentiate microbial strains without having
      previous knowledge of the membrane molecules or structural changes present in
      that particular microorganism. The present review focuses on aptamers, SELEX
      procedures, and aptamer-based biosensors (aptasensors) for the detection of
      pathogenic microorganisms and viruses. Special emphasis is placed on nanoparticle
      based platforms.

PMID- 19117749
TI  - Vulvar squamous cell carcinoma development after diagnosis of VIN increases with
      age.
AB  - OBJECTIVE: The purpose of the present study is to investigate the trends in
      incidence of both usual (u) and differentiated (d) vulvar intraepithelial
      neoplasia (VIN) separately, their malignant potential and the relation with other
      HPV related anogenital lesions in the Netherlands during a 14-year-period.
      METHODS: The incidences of both types of VIN and vulvar SCC were retrieved from
      the Nationwide Netherlands Database of Histo- and Cytopathology. Population data
      were retrieved from the Database of Statistics Netherlands. RESULTS: In the study
      period, the incidence of uVIN and dVIN increased, while the incidence of vulvar
      SCC remained stable. The overall percentage of uVIN patients that were later
      diagnosed with vulvar SCC was 5.7%, which was significantly lower than the
      percentage for dVIN patients (32.8%). In addition to this 5.6-fold increased
      conversion rate, the time of progression from dVIN to SCC development was
      significantly shorter than that of uVIN (p=0.005). Percentage of uVIN patients
      that were later diagnosed with SCC significantly increased with age (p=0.005),
      whereas the time to SCC significantly shortened with age (p=0.05). Forty-one
      percent of uVIN patients had a past, concomitant or future HPV-associated lesion
      of the lower genital tract, which is in contrast to the 3% for dVIN patients.
      CONCLUSIONS: An increase in diagnoses of both uVIN and dVIN has not led to an
      increase in vulvar SCC incidence. The malignant potential of dVIN is higher than
      that for uVIN. For uVIN the malignant potential increases with age.

PMID- 19117750
TI  - Evaluation of data quality in the cancer registry: principles and methods. Part
      I: comparability, validity and timeliness.
AB  - The value of the modern cancer registry and its ability to carry out cancer
      control activities rely heavily on the underlying quality of its data and the
      quality control procedures in place. This two-part review provides an update of
      the practical aspects and techniques for addressing data quality at the cancer
      registry. This first installment of the review examines the factors influencing
      three of the four key aspects, namely, the comparability, validity and timeliness
      of cancer registry data. Comparability of cancer data may be established through
      a comprehensive review of the registration routines in place. Validity is
      examined via numerical indices of that permit comparisons with other registries,
      or, within a registry, over time, or with respect to specified subsets of cases.
      There are no international guidelines for timeliness at present, although
      specific standards for the abstraction and reporting of registry have been set
      out by certain organisations.

PMID- 19117751
TI  - Removal of Cu(II) ions by biosorption onto powdered waste sludge (PWS) prior to
      biological treatment in an activated sludge unit: a statistical design approach.
AB  - Biological treatment of synthetic wastewater containing Cu(II) ions was realized
      in an activated sludge unit with pre-adsorption of Cu(II) onto powdered waste
      sludge (PWS). Box-Behnken experimental design method was used to investigate
      Cu(II), chemical oxygen demand (COD) and toxicity removal performance of the
      activated sludge unit under different operating conditions. The independent
      variables were the solids retention time (SRT, 5-30 d), hydraulic residence time
      (HRT, 5-25 h), feed Cu(II) concentration (0-50 mg L(-1)) and PWS loading rate (0
      4 g h(-1)) while percent Cu(II), COD, toxicity (TOX) removals and the sludge
      volume index (SVI) were the objective functions. The data were correlated with a
      quadratic response function (R2=0.99). Cu(II), COD and toxicity removals
      increased with increasing PWS loading rate and SRT while decreasing with the
      increasing feed Cu(II) concentration and HRT. Optimum conditions resulting in
      maximum Cu(II), COD, toxicity removals and SVI values were found to be SRT of 30
      d, HRT 15 h, PWS loading rate 3 g h(-1) and feed Cu(II) concentration of less
      than 30 mg L(-1).

PMID- 19117752
TI  - Effect of salinity on vanadate biosorption by Halomonas sp. GT-83: preliminary
      investigation on biosorption by micro-PIXE technique.
AB  - Thirty-eight soil samples were collected from crude oil contaminated land in
      south of Iran. Initial screening of a total of 100 bacterial isolates, resulted
      in the selection of one isolate with maximum adsorption capacity of 52.7 mg
      vanadate/g dry weight. It was tentatively identified as Halomonas sp. according
      to morphological and biochemical properties and named strain GT-83. Removal of
      vanadate by biosorption with Halomonas sp. GT-83 was very sensitive to solution
      pH. Vanadate adsorption decreased with increasing pH, with maximum adsorption
      capacities achieved in at pH 3.0 in the absence and in the presence of increasing
      concentrations of salt. Vanadate-salt biosorption studies were also performed at
      this pH value. Equilibrium uptakes of vanadate increased with increasing vanadate
      concentration up to 600 mg/l. Maximum metal removal (91.8%) took place at pH 3.0
      with initial vanadate concentration of 100mg/l, which got reduced (84.8%) in the
      presence of 50 g/l salt. The equilibrium sorption data were analyzed by using
      Freundlich isotherm. The specific uptake of vanadate increased at low cell
      concentration and decreased when cell concentration exceeded 0.75 g/l. The paper
      also demonstrates the potential value of micro-PIXE in biosorption studies.

PMID- 19117753
TI  - Process characteristics and products of olive kernel high temperature steam
      gasification (HTSG).
AB  - Exploitation of olive kernel for bioenergy production, with respect to the green
      house gases (GHGs) mitigation, is the main aim of this work. In this study, olive
      kernels were used as a solid biofuel, and high temperature steam gasification
      (HTSG) was investigated, in the fixed bed unit at KTH Sweden, with regard to
      hydrogen maximization in the produced gasification gas. Experiments were carried
      out in a temperature range of 750-1050 degrees C, with steam as the gasifying
      agent. The behaviour of olive kernels, under residence times from 120 up to 960
      s, has been studied. At 1050 degrees C, a medium to high calorific value gas was
      obtained (LHVgas=13.62 MJ/Nm3), while an acquired H2/CO molar ratio equal to four
      proved that olive kernel HTSG gasification could be an effective technology for a
      hydrogen-rich gas production (approximately 40%vv H2 in the produced gasification
      gas at 1050 degrees C). The produced char contained 79%ww of fixed carbon, low
      chlorine and sulphur content, which enables it for further re-use for energetic
      purposes. Tar content in the produced gas at 750 degrees C was 124.07 g/Nm3,
      while a 1050 degrees C at 79.64% reduction was observed and reached the value of
      25.26 g/Nm3.

PMID- 19117754
TI  - Bone selective effect of an estradiol conjugate with a novel tetracycline-derived
      bone-targeting agent.
AB  - In this study a novel bone-targeting agent containing elements of the
      tricarbonylmethane system of ring A of tetracycline was developed and was shown
      to bind to the mineral constituent of bone, hydroxyapatite. Conjugation of this
      bone-targeting agent to estradiol resulted in a bone-targeted estrogen (BTE(2)
      A1) with an enhanced ability to bind to hydroxyapatite. In an ovariectomized rat
      model of osteoporosis a partial separation of the skeletal effects of estradiol
      from the uterine effects was observed following subcutaneous administration of
      BTE(2)-A1. This novel bone-targeting estradiol delivery system has the potential
      to improve the safety profile of estradiol in the treatment of osteoporosis.

PMID- 19117755
TI  - Electrochemical activity of holotransferrin and its electrocatalysis-mediated
      process of artemisinin.
AB  - Holotransferrin, the iron (III) transport protein in the blood, can significantly
      increase the anticancer activity of artemisinin, which is isolated from the
      Chinese plant qinghaosu. This paper investigates the action process of
      holotransferrin-induced electrocatalytic reduction of artemisinin by
      spectroscopic and electrochemical techniques. Results show that
      holotransferrin(Fe(III)) is the electrochemical sites of holotransferrin, which
      can catalyze the reduction of artemisinin through lowering the overpotential by
      about 80 mV. Compared with the different electrochemical behaviors of artemisinin
      with apotransferrin and holoprotein (apotransferrin in the presence of Fe(III)),
      respectively, it demonstrates that holotransferrin(Fe(III)) plays an important
      role in the electrocatalytic reduction of artemisinin, which can catalyze the
      cleavage of the endoperoxide bridge in artemisinin. A reliable two-step process
      is proposed to explain that artemisinin is activated by holotransferrin(Fe(III))
      mediated electrocatalytic reduction. These results can provide further
      information for better understanding the anticancer action of holotransferrin
      conjugated artemisinin.

PMID- 19117756
TI  - Investigation of ketone warheads as alternatives to the nitrile for preparation
      of potent and selective cathepsin K inhibitors.
AB  - Amino ketone warheads were explored as alternatives to the nitrile group of a
      potent and selective cathepsin K inhibitor. The resulting compounds were potent
      and selective inhibitors of cathepsin K and these nitrile replacements had a
      significant effect on metabolism and pharmacokinetics.

PMID- 19117757
TI  - Japonicones A-D, bioactive dimeric sesquiterpenes from Inula japonica Thunb.
AB  - Four new dimeric sesquiterpene lactones japonicones A-D (1-4), comprised by
      eudesmane and guaiane sesquiterpenes, were isolated from the aerial part of Inula
      japonica Thunb. The structures and stereochemistry of 1-4 were elucidated by use
      of 2D NMR spectroscopic techniques, X-ray crystallography and modified Mosher
      method. Japonicone A (1) showed the most potent cytotoxicities against four tumor
      cell lines, A549, LOVO, CEM and MDA-MB-435.

PMID- 19117758
TI  - Efficient synthesis and biological evaluation of 1,2,9-trisubstituted 1,9-dihydro
      6H-purin-6-ones.
AB  - The carbodiimides 4, obtained from aza-Wittig reactions of iminophosphorane 3
      with aromatic isocyanates, reacted with amines in the presence of a catalytic
      amount of RO(-)Na(+) to give the 1,2,9-trisubstituted 1,9-dihydro-6H-purin-6-ones
      6 in good yields. Compound 6 exhibited cytotoxicity against various cancer cells.
      For example, compounds 6b showed the best inhibition activities against KB, HepG2
      and OVCAR3 with IC(50) 9.5, 20.4 and 10.0 microM.

PMID- 19117759
TI  - New quinoline NK3 receptor antagonists with CNS activity.
AB  - Lead optimisation starting from the previously reported selective quinoline NK(3)
      receptor antagonists talnetant 2 (SB-223412) and 3 (SB-222200) led to the
      identification of 3-aminoquinoline NK(3) antagonist 10 (GSK172981) with excellent
      CNS penetration. Investigation of a structurally related series of sulfonamides
      with reduced lipophilicity led to the discovery of 20 (GSK256471). Both 10 and 20
      are high affinity, potent NK(3) receptor antagonists which despite having
      different degrees of CNS penetration produced excellent NK(3) receptor occupancy
      in an ex vivo binding study in gerbil cortex.

PMID- 19117760
TI  - Structure-based virtual screening for novel inhibitors of the sarco/endoplasmic
      reticulum calcium ATPase and their experimental evaluation.
AB  - A public compound library with 260,000 compounds was screened virtually by
      computational docking for novel inhibitors of the transmembrane enzyme
      sarco/endoplasmic reticulum calcium ATPase (SERCA). Docking was performed with
      the program GOLD in conjunction with a high resolution X-ray crystal structure of
      SERCA. Compounds that were predicted to be active were tested in bioassays.
      Nineteen novel compounds were discovered that were capable of inhibiting the ATP
      hydrolysis activity of SERCA at concentrations below 50 microM. Crucial
      enzyme/inhibitor interactions were identified by analyzing the docking-predicted
      binding poses of active compounds. Like other SERCA inhibitors, the newly
      discovered compounds are of considerable medicinal interest because of their
      potential for cancer chemotherapy.

PMID- 19117761
TI  - Design, synthesis and biological evaluation of novel stilbene-based antitumor
      agents.
AB  - A series of novel stilbene derivatives has been synthesized and studied with the
      main goal to investigate SAR of the amino compound 1a, as well as to improve its
      water solubility, a potentially negative aspect of the molecule that could be a
      serious obstacle for a pre-clinical development. We have obtained derivatives
      with good cytotoxic activity, in particular, the derivatives 5c and 6b could
      represent two novel leads for further investigation. Compound 8b, a morpholino
      carbamate derivative, prodrug of 1a, has a very good solubility in water, and is
      active in suppressing growth of tumor cells at a concentration of 5000 nM, which
      is a concentration 100 times higher than the parent stilbene 1a.

PMID- 19117762
TI  - Calculations of the thermal and fast neutron fluxes in the Syrian miniature
      neutron source reactor using the MCNP-4C code.
AB  - The MCNP-4C code, based on the probabilistic approach, was used to model the 3D
      configuration of the core of the Syrian miniature neutron source reactor (MNSR).
      The continuous energy neutron cross sections from the ENDF/B-VI library were used
      to calculate the thermal and fast neutron fluxes in the inner and outer
      irradiation sites of MNSR. The thermal fluxes in the MNSR inner irradiation sites
      were also measured experimentally by the multiple foil activation method ((197)Au
      (n, gamma) (198)Au and (59)Co (n, gamma) (60)Co). The foils were irradiated
      simultaneously in each of the five MNSR inner irradiation sites to measure the
      thermal neutron flux and the epithermal index in each site. The calculated and
      measured results agree well.

PMID- 19117763
TI  - Hormones in the grains and roots in relation to post-anthesis development of
      inferior and superior spikelets in japonica/indica hybrid rice.
AB  - Grain filling is usually not adequate in later-flowering inferior spikelets in
      japonica/indica (J/I) hybrid rice (Oryza sativa) although it shows stronger
      hybrid vigor than indica/indica (I/I) hybrid. This study investigated the
      potential causes by examining changes in zeatin (Z)+zeatin riboside (ZR), indole
      3-acetic acid (IAA), gibberellins (GAs, GA(1)+GA(4)), and abscisic acid (ABA) in
      spikelets and roots during the grain filling period. The inferior spikelets of
      J/I hybrid exhibited low rate of endosperm cell division and slow grain filling.
      During the early grain filing period, they had less Z+ZR, IAA, and ABA, but more
      GAs, than the earlier-flowering superior spikelets. If compared to the inferior
      spikelets of the I/I hybrid, the J/I inferior spikelets also had less Z+ZR, IAA,
      and ABA. Rates of endosperm cell division and grain filling were positively and
      significantly correlated with Z+ZR and ABA contents in both grains and roots or
      IAA in grains, whereas not significantly correlated with GAs either in grains or
      roots or IAA in roots. Applications of kinetin, IAA, or ABA to spikelets, or
      kinetin and ABA to roots, enhanced cell division and grain filling in the
      inferior spikelets. Results suggest that low contents of cytokinins and ABA in
      both grains and roots and low contents of IAA in grains may result in the poor
      filling of inferior spikelets in the J/I hybrid.

PMID- 19117764
TI  - Dealing with aberrant vessels in radial forearm flaps - report of a case and
      review of literature.
AB  - INTRODUCTION: Anomalies of the radial artery are uncommon. A brief tabulated
      review of the literature is presented. CASE REPORT: We report a rare anomaly of
      the forearm vascular anatomy we encountered when elevating a radial forearm free
      flap. This is a previously unreported anatomical variation. The radial artery
      divided into medial and lateral branches (accompanied by their respective venae
      commitantes) about 1.5 cm below the bifurcation of the brachial artery. The skin
      paddle was predominantly supplied by the aberrant medial branch and was raised on
      this branch along with its venae commitantes up to the point of division.
      CONCLUSION: This case highlights the need for vigilance when raising free flaps
      and the techniques employed to avoid compromising both limb and skin paddle
      perfusion.

PMID- 19117765
TI  - Oropharyngeal airway changes following bimaxillary surgery in Class III female
      adults.
AB  - AIM: The aim of this study was to evaluate oropharyngeal airway changes following
      Le Fort I maxillary advancement and impaction with mandibular setback in Class
      III deformity. SUBJECTS AND METHODS: 53 female Class III patients (mean age:
      24.9+/-0.8 years) had Le Fort I maxillary advancement with impaction, and
      mandibular setback osteotomies. Lateral cephalograms were taken before (T0), one
      week postoperatively (T1) and 1.3+/-0.2 years after (T2) bimaxillary surgery.
      Paired t and Pearson tests were used to evaluate the changes. RESULTS: The
      mandibular plane-hyoid, upper retropalatal airway space (URP) and hyoid to
      horizontal reference plane (HY-HOR) distances significantly increased and the
      third vertebra to menton, hyoid to vertical reference plane (HY-VER) distances
      decreased in the T0-T1 period. Relapses were found in mandibular plane to hyoid
      (MP-HY), URP, HY-HOR, third cervical vertebra to menton (C3-Me) and HY-VER
      distances in T1-T2 period. Correlations were found between the mandibular
      retraction and increases of the narrowest retropalatal (r: 0.29, p<0.05) and
      lowest retropalatal airway spaces (r: -0.30, p<0.05) and posterior movement of
      hyoid (r: 0.60, p<0.001). CONCLUSIONS: Bimaxillary surgery caused an increase in
      the URP, together with posterior and inferior movement of hyoid bone one week
      postoperatively. Some relapse was found in these changes over one year later.

PMID- 19117766
TI  - Progressive right ventricular failure is not explained by myocardial ischemia in
      a pig model of right ventricular pressure overload.
AB  - BACKGROUND: Current concepts of acute pulmonary embolism suggest that right
      ventricular (RV) dilatation and failure are the consequence of pressure overload
      induced RV hypoperfusion and ischemia. METHODS: Sixteen human-sized hybrid pigs
      were instrumented for the measurement of RV and aortic pressure, aortic and right
      coronary artery blood flow (RCA BF), RV oxygen consumption (RV MVO(2)) and RV
      free wall segment length. The pulmonary artery was constricted (PAC) to increase
      RV peak pressure acutely 2.5-fold (from 27+/-2 to 64+/-3 mmHg, n=9), and the
      constriction was maintained for 6h. RESULTS: At 10 min after PAC, a RV work index
      (RVWI, RV pressure-segment length loops) was increased 2.3-fold, indicating an
      initial RV adaptation to increased afterload. At 1h, 3h and 6h after PAC,
      however, RVWI decreased progressively towards control levels, while RCA BF and RV
      MVO(2) continued to increase. The arterial-coronary venous pH difference did not
      increase throughout the protocol. Arterial troponin T concentration increased
      from 0.08+/-0.03 to 0.80+/-0.20ng/ml at 6h after PAC. None of the parameters
      changed in control animals (n=7). CONCLUSION: We conclude that in our model RV
      failure during PAC develops in spite of increased coronary blood flow and MVO(2).
      Thus, mechanisms different from ischemia may contribute to progressive RV failure
      after pulmonary embolism.

PMID- 19117768
TI  - The effects of muscle architectural change with a pre-motion silent period on the
      subsequent muscular output during rapid voluntary movement.
AB  - This study aimed to determine the characteristics of the in vivo behaviour of
      human muscle architecture during a pre-motion silent period (PMSP) using
      ultrasonography. Subjects were requested to perform rapid knee extension with
      vertical jumping. Electromyographic signals were recorded from the vastus
      lateralis (VL), vastus medialis, and biceps femoris muscles. Ultrasonic images
      were recorded from the VL. We found that the cross point between the fascicle and
      deep aponeurosis in the VL moved to the distal side before the rapid vertical
      jumps with PMSP. This cross point movement with PMSP was of low amplitude (mean:
      1.0+/-0.3mm) and velocity (22.2+/-6.1mm/s). The amplitude and velocity of the
      cross point movement were significantly positively related to the angular peak
      velocity of knee extensor during rapid vertical jumping in trials with PMSP.
      These results suggest that although low levels of pre-movement muscle
      architectural change with PMSP may be the result of muscle relaxation behaviour
      rather than the result of muscle stretching behaviour, this pre-movement effect
      can influence subsequent muscular performance during a rapid voluntary movement.
      PMSP may allow pre-movement muscle architectural change to generate a better
      muscular condition to increase neural activation during the subsequent rapid
      voluntary contraction.

PMID- 19117767
TI  - Endogenous hydrogen sulfide reduces airway inflammation and remodeling in a rat
      model of asthma.
AB  - Endogenous hydrogen sulfide (H(2)S) is hypothesized to have an important role in
      systemic inflammation. We investigated if endogenous H(2)S may be a crucial
      mediator in airway inflammation and airway remodeling in a rat model of asthma
      and if endogenous H(2)S may exert its anti-inflammatory effect by inhibiting
      inducible nitric oxide synthase (iNOS)/NO pathway. Cystathionine-gamma-lyase
      (CSE; a H(2)S-synthesizing enzyme) was mainly expressed in airway and vascular
      smooth muscle cells in rat lung tissue. Levels of endogenous H(2)S was decreased
      in pulmonary tissue in ovalbumin (OVA)-treated rats. Exogenous administration of
      NaHS alleviated airway inflammation and airway remodeling: peak expiratory flow
      (PEF) increased, goblet cell hyperplasia and collagen deposition score decreased,
      with decreased total cells recovered from bronchoalveolar fluid (BALF) and influx
      of eosinophils and neutrophils. The H(2)S levels of serum and lung tissue were
      positively correlated with PEF and negatively correlated with the level of
      eosinophils and neutrophils in BALF, score of lung pathology. NaHS treatment
      significantly attenuated pulmonary iNOS activation in OVA-treated rats. These
      results suggest that the CSE/H(2)S pathway plays an anti-inflammatory and anti
      remodeling part in asthma pathogenesis and could be a novel target in prevention
      and treatment of asthma.

PMID- 19117769
TI  - Survival analysis in men undergoing radical prostatectomy at an age of 70 years
      or older.
AB  - OBJECTIVES: To compare comorbidity measures and to analyze survival rates in men
      undergoing radical prostatectomy at age 70 years or older. MATERIALS AND METHODS:
      A total of 329 consecutive patients aged 70 or more years who underwent radical
      prostatectomy between 1992 and 2004 were studied. The patients were stratified by
      5 comorbidity classifications, tumor stage, Gleason score, and PSA value.
      Mortality was subdivided into overall, comorbid, competing, prostate cancer
      specific, and second cancer-specific mortality. Competing risk and Kaplan-Meier
      survival curves as well as Mantel-Haenszel hazard ratios were calculated.
      Comparisons were made with the log-rank test. Cox proportional hazard models were
      used to determine the independent significance of prognostic variables. RESULTS:
      Considering the dose-response relationship, P values and the discrimination of 2
      risk groups, the Charlson score was the best of the tested comorbidity
      classifications in men selected for radical prostatectomy at age 70 years or
      older. Beside the tumor-related factors Gleason score 8-10 (hazard ratio 2.61, P
      = 0.0234) and lymph node involvement (hazard ratio 2.89, P = 0.0145), a Charlson
      score of 1 or greater was identified as an independent predictor of overall
      mortality (hazard ratio 2.16, P = 0.0441). Without comorbidity or adverse tumor
      related risk factors, elderly men had an excellent 10-year overall survival
      probability (77% to 100%, depending on the classification used), whereas 10-year
      overall survival was distinctly poor in the presence of lymph node metastases
      (30%) or Gleason score 8-10 disease (33%). CONCLUSIONS: The Charlson comorbidity
      score may be used to stratify men selected for radical prostatectomy at age 70
      years or older and to estimate long-term survival probability. In the absence of
      adverse tumor-related parameters or serious comorbidity, long-term survival
      probability is excellent in this subgroup.

PMID- 19117770
TI  - Genetic polymorphism of glutathione S-transferases M1 and T1 in Egyptian patients
      with bilharzial bladder cancer.
AB  - OBJECTIVE: To assess the influence of glutathione S-transferases M1 and T1 (GSTM1
      and T1) genotype on the risk of bladder cancer in patients with urinary
      bilharziasis. MATERIALS AND METHODS: This study was designed as a case-control
      study that involved 60 individuals who were enrolled into 3 equal groups. The
      first one included patients with bilharzial bladder cancer, the second one had
      those with nonmalignant urinary bilharziasis, and the last one was the control
      group. All of the participants were adult males, nonsmokers, and with matched
      ages. All of them underwent an assessment of the serum level of the total GST
      concentration and the polymerase chain reaction (PCR) was used for determination
      of the GSTM1 and T1 genotypes. RESULTS: The lower most GST enzyme concentration
      was reported in patients with bilharzial bladder cancer (26 +/- 4.4 ng/ml) with
      significant difference between it and that of the second group (36.8 +/- 4.1
      ng/ml, P < 0.05) and that of the controls (40.4 +/- 4 ng/ml, P < 0.005). The PCR
      results have demonstrated that the frequency of combined GSTM1 and T1 genes
      deletion (M1-ve T1-ve) was significantly higher in cases of bladder cancer (40%)
      than those of the controls (5%, P < 0.005) and those of the second group (10%, P
      < 0.05). The unconditional logistic regression test revealed that patients with
      urinary bilharziasis and combined GSTM1 and T1 genes deletion are at a
      significant risk for malignant transformation (OR = 6.3, P < 0.05). CONCLUSIONS:
      Patients with urinary bilharziasis and GSTM1-ve and T1-ve genes might be at
      increased risk of bladder cancer. However, larger studies are needed for
      confirmation of these results.

PMID- 19117772
TI  - MicroRNAs and cancer: current state and future perspectives in urologic oncology.
AB  - MicroRNAs (miRNAs) are small non-protein coding RNAs that regulate basic cellular
      processes and are associated with cancer characteristics. It is the aim of this
      review to describe the basics of the biogenesis and function of miRNAs, provide
      their role in tumorigenesis, and demonstrate their clinical potential in general
      and especially in urologic oncology. For that purpose, a PubMed search up to
      August 2008 was conducted using the Medical Subject Heading (MeSH) terms for
      miRNAs alone and the urological carcinomas of kidney, prostate, bladder, testis,
      and penis combined with the Boolean operator "AND". Until August 2008, about
      3,500 miRNA publications were included in the PubMed database. It has been
      estimated that about 1,500 would be published in 2008 alone. Several miRNA
      expression studies and corresponding functional experiments in various cancers
      showed the important role of miRNAs in cancer initiation and progression and
      proved their potential as diagnostic, prognostic, and predictive biomarkers and
      as basis for novel therapeutic strategies. However, in uro-oncology, only a few
      miRNA related articles (22 for prostate, 4 for kidney, 3 for bladder, and 6 for
      testis) were published. Cancer-specific expressions of miRNA patterns were shown,
      but the limited and partly inconsistent data underscore that we are at an early
      stage regarding this topic in urology. In spite of the obvious significance of
      miRNAs in malignant tumors, the relatively sparse data on miRNAs in uro-oncology
      clearly advocate that this area should be more intensively studied. Detailed
      understanding of the characteristic miRNA abnormalities could contribute to novel
      approaches in diagnosis and treatment of urological tumors.

PMID- 19117771
TI  - Does the presence of hydronephrosis on preoperative axial CT imaging predict
      worse outcomes for patients undergoing nephroureterectomy for upper-tract
      urothelial carcinoma?
AB  - OBJECTIVES: Hydronephrosis at the time of diagnosis of bladder cancer is
      associated with advanced disease and is a predictor of poorer outcomes. There is,
      however, limited information addressing whether a similar relationship exists for
      upper-tract urothelial carcinoma (UTUC). We investigate the prognostic impact of
      hydronephrosis on preoperative axial imaging on clinical outcomes after radical
      nephroureterectomy. MATERIALS AND METHODS: The records for 106 patients with UTUC
      who underwent radical nephroureterectomy at 2 medical centers were reviewed.
      Preoperative computed tomography (CT) images were evaluated for ipsilateral
      hydronephrosis by radiologists blinded to clinical outcomes. Association of
      hydronephrosis with pathologic features and oncologic outcomes after surgery was
      assessed. RESULTS: Sixty-seven men and 39 women with a median age of 69 years
      (range, 36 to 90) were evaluated. One-third of these patients had muscle invasive
      disease or greater (>=T2), 44% had high grade tumors, and 3% had lymph node (LN)
      metastases. At a median follow-up of 47 months (range, 1 to 164), 43% of patients
      experienced disease recurrence, 18% developed metastasis, and 12% died of their
      cancer. Thirty-nine patients (37%) had hydronephrosis on preoperative axial
      imaging; 35% of these patients had ureteral tumors, and 27% had multifocal
      disease. The presence of hydronephrosis was associated with advanced pathologic
      stage (P = 0.03) and disease in the ureter (vs. renal pelvis) (P = 0.007).
      Hydronephrosis was a predictor of non-organ confined disease on final pathology
      (hazard ratio [HR] 3.7, P = 0.01). On preoperative multivariable analysis
      controlling for age, gender, tumor location, ureteroscopic biopsy grade, and
      urinary cytology, hydronephrosis was independently associated with cancer
      metastasis (HR 8.2, P = 0.02) and cancer-specific death (HR 12.1, P = 0.03).
      CONCLUSIONS: Preoperative hydronephrosis on axial imaging is associated with
      features of aggressive disease and predicts advanced pathologic stage for UTUC.
      Hydronephrosis can be a valuable prognostic tool for preoperative planning and
      counseling regarding disease outcomes.

PMID- 19117773
TI  - Matrix metalloproteinase-2 polymorphism is associated with prognosis in prostate
      cancer.
AB  - OBJECTIVE: Prostate cancer (PCa) is the most frequent tumor in males in Brazil.
      Single nucleotide polymorphisms (SNP) have been demonstrated in the promoter
      region of matrix metalloproteinases (MMPs) genes and have been associated with
      development and progression of some cancers. In this study, our aim was to
      investigate a possible relation between polymorphism of the promoter region of
      the MMP2 gene and classical prognostic parameters in prostate cancer. MATERIALS
      AND METHODS: Genomic DNA was extracted using conventional protocols. The DNA
      sequence containing the polymorphic site was amplified by real-time polymerase
      chain reaction, using fluorescent probes (TaqMan). RESULTS: In patients with
      tumors of a higher stage (pT3), a polymorphic allele in the MMP2 gene was more
      frequent (P = 0.026) than in patients with lower tumor stage. A polymorphic
      allele in the MMP2 gene was more frequent in Gleason >= 7 than in Gleason <= 6 (P
      = 0.042). CONCLUSIONS: We conclude that MMP2 polymorphism can be used together
      with pathological stage and Gleason score to identify patients with worse
      prognosis. Our results illustrate the potential use of MMP2 SNP as a molecular
      marker for prostate cancer.

PMID- 19117775
TI  - Measurement of health-related quality of life with the Dutch translated Aberdeen
      Varicose Vein Questionnaire before and after treatment.
AB  - OBJECTIVE: This clinical trial evaluated the use of the Dutch translated Aberdeen
      Varicose Vein Questionnaire (AVVQ) and SF-36 before and after treatment in
      patients with clinical-severity classes 1-6 venous disease of the lower limb.
      METHODS: A total of 145 patients with symptomatic venous disease of the leg were
      included. Numbers of patients were evenly distributed among the six clinical
      severity classes 1-6 (clinical, aetiology, anatomy and pathophysiology; CEAP).
      Patients completed two preoperative AVVQ questionnaires and one short-form health
      survey with 36 items (SF-36) questionnaire to evaluate test-re-test reliability
      of the AVVQ. Patients completed one postoperative AVVQ and SF-36 to evaluate the
      effect of treatment. RESULTS: The test (99%) and re-test responses (97%) of the
      AVVQ were sufficient. Internal consistency of the Dutch translated AVVQ showed a
      Cronbach's alpha of 0.76. Correlation of test and re-test of the AVVQ was high
      (rho=0.86, P<0.001). A significant negative association, by Spearman's
      correlation coefficient, was found between the preoperative baseline Dutch
      translated AVVQ score and all eight domains of the preoperative SF-36 (P<0.001).
      These significant associations were also found in the postoperative scores. The
      mean preoperative AVVQ score of 19.5 (SD 11.8) and mean postoperative AVVQ score
      of 16.1 (SD 12.0) differed significantly (P<0.01). Analysis of three subgroups of
      clinical-severity classes (C1-2, C3-4 and C5-6) showed significant score changes
      before and after surgery (P<0.01). Preoperative and postoperative SF-36 scores
      were not significantly different. CONCLUSIONS: This study established the use of
      the Dutch translated AVVQ as a valid, health-related quality of life (QOL)
      questionnaire for measuring QOL before and after treatment in patients with
      clinical-severity classes 1-6 venous disease of the leg.

PMID- 19117774
TI  - Patient risk stratification using Gleason score concordance and upgrading among
      men with prostate biopsy Gleason score 6 or 7.
AB  - PURPOSE: To define the impact of discordant Gleason sum (GS) between prostate
      biopsy (Pbx) tissue and radical prostatectomy (RP) specimen among men initially
      diagnosed with Gleason 6 or 7 prostate adenocarcinoma. MATERIALS AND METHODS: We
      evaluated patients diagnosed with GS 6 or 7 and treated primarily with RP. We
      defined the frequency of GS discordance between Pbx and RP pathology reports. We
      analyzed pretreatment parameters associated with GS discordance and compared
      immediate postprostatectomy outcome variables across patient groups defined by
      their GS and concordance. We then conducted survival analysis for biochemical
      recurrence across patient groups defined by their GS and concordance status.
      RESULTS: Among patients with GS 6 on Pbx, 681/1,847 (36.86%) patients were
      upgraded to GS 7 or higher after RP. Surgical margin, capsular involvement,
      seminal vesicle, and nodal involvement status were more favorable in patients
      with concordant Pbx and RP specimen with GS 6 (P < 0.0001). Patients with smaller
      transrectal ultrasound (TRUS) prostate volume were found to have higher PSA
      densities and were more likely to be upgraded at RP. Multivariate survival
      analysis also predicted fewer biochemical recurrence events over time in men with
      concordant Pbx tissue and RP specimen of GS 6 vs. 6/7 or 7/7 (P = 0.0025)
      controlling for other relevant covariates. CONCLUSIONS: GS discordance between
      Pbx tissue and RP specimens among prostate cancer patients initially diagnosed
      with either GS 6 or 7 adenocarcinoma of the prostate is substantial. This
      discordance has potential clinical significance in predicting oncologic outcomes.

PMID- 19117776
TI  - Homotopic stimulation can reduce the area of allodynia in patients with
      neuropathic pain.
AB  - Allodynia is a common, troublesome feature of neuropathic pain conditions. In a
      previous study of postherpetic neuralgia we observed that repeated tactile
      stimulation appeared to reduce the size of the area of allodynia in some
      patients. We have undertaken a pragmatic clinical study to characterise this
      phenomenon in neuropathic pain patients with a range of different aetiologies.
      Neuropathic pain patients with a discrete area of tactile allodynia were
      recruited (n=20). We assessed the sensitive area using punctate and dynamic
      tactile stimuli, and thermal quantitative sensory testing. On two separate
      testing visits, the patients had repeated (10x over 1 min) noxious heat or cotton
      bud strokes applied to the affected site or contralaterally. Tactile stimulation
      of the affected area evoked pain (median 7 NRS) and a reduction (>30%) in the
      area of allodynia in 9/18 patients (maximum -48+/-9%, after 20 min), although the
      intensity of allodynic pain was unchanged. This effect persisted for over 1h and
      was present the following day in all patients tested (n=5/5). No subjects showed
      an increase in area after allodynic stimulation. There was no change in heat pain
      threshold at a distant site following allodynic stimulation, suggesting no
      activation of diffuse noxious inhibitory control. Repeated thermal noxious
      stimulation (median NRS 7) could also elicit changes (>30%) in the area of
      allodynia in some patients (reductions in 7/20, increases in 3/20). Thus, we have
      found that a brief period of homotopic painful stimulation can reduce the area of
      allodynia in around half of patients with established neuropathic pains.

PMID- 19117777
TI  - Lateral rectus restriction secondary to traumatic orbital exostosis.
AB  - Bony exostoses can occur at the site of a fracture but are rare in facial bones.
      We report a case of lateral rectus restriction secondary to a traumatic exostosis
      in the lateral orbital wall with resolution of diplopia after surgical removal of
      the lesion. Although orbital masses may cause extraocular muscle restriction, to
      our knowledge, restriction secondary to an exostosis has not been previously
      reported. A bony exostosis should therefore be included in the differential
      diagnosis of mechanical restriction of extraocular muscle movement, and surgical
      treatment is recommended in symptomatic patients.

PMID- 19117778
TI  - Management of vertical deviations after vertical rectus transposition surgery.
AB  - PURPOSE: To describe options for the management of vertical deviations after
      vertical rectus muscle transposition surgery (VRT). METHODS: Retrospective case
      series including 7 children who underwent VRT for esotropic Duane syndrome and
      developed the complication of a vertical deviation. RESULTS: Eighty-two
      consecutive children underwent VRT for Duane syndrome. Seven eyes of 7 patients
      (4 boys, 3 girls) were found to have induced vertical deviations postoperatively.
      Average length of follow-up was 12.7 months (range, 3-28 months). Median induced
      vertical deviation was 10.1(Delta) (range, 8-12). All patients required only one
      additional surgery to ameliorate the vertical deviation. At final follow-up, the
      mean vertical tropic deviation was 0. Six patients were operated on within 4 days
      of VRT. Surgical strategies included recession of one vertical rectus muscle and
      repositioning of a posterior fixation suture. CONCLUSIONS: In children undergoing
      VRT for esotropic Duane syndrome, the complication of a vertical deviation
      occurred in 8.5% of cases. The vertical deviation was completely ameliorated in
      each case by one surgical procedure involving recession of one of the transposed
      muscles.

PMID- 19117779
TI  - Design and QSAR study of analogs of gamma-tocotrienol with enhanced
      antiproliferative activity against human breast cancer cells.
AB  - Quantitative structure-activity relationships (QSAR) study has been performed for
      two sets of the antitumor drugs against human breast cancer MCF-7 cell lines,
      alpha-tocopherol and cholesterol derivatives. Constitutional, geometrical,
      physico-chemical and electronic descriptors (using the density functional theory,
      B3LYP/6-31G (d,p) basis set) were computed and analyzed. The most relevant of
      these descriptors were grouped and multiple linear regressions have been carried
      out. Optimal QSAR models with three and four variables, R(2)>0.95 and cross
      validation parameter q(pre)(2)>0.88, were selected. Based on the QSAR study,
      novel vitamin-E derivatives (compounds D-1 and D-2) were designed and their
      antiproliferative activities were evaluated using the proposed regression models.
      Calculated antiproliferative activities of the designed compounds, IC(50) (D-1):
      3.09 microM and IC(50) (D-2): 3.54 microM, were significantly stronger than
      anticancer effect of the other analyzed compounds IC(50): 4-1461 microM.

PMID- 19117780
TI  - CoMFA and CoMSIA studies on thiazolidin-4-one as anti-HIV-1 agents.
AB  - Comparative molecular field analysis (CoMFA) and comparative molecular similarity
      indices analysis (CoMSIA) were performed on thiazolidin-4-one class of compounds
      as HIV-1 reverse transcriptase (HIV-1 RT) inhibitors using global minima and
      crystal structure conformations. Results obtained from the crystal structure
      based model yielded superior statistical data (r(cv)(2) values of 0.683 for CoMFA
      and 0.678 for CoMSIA) when compared to those obtained by the global minima-based
      model (r(cv)(2) values of 0.625 and 0.654 for CoMFA and CoMSIA, respectively).
      The models were validated using an external test set of 47 compounds. The
      predictive r(2) values for the crystal-based CoMFA and CoMSIA models were 0.735
      and 0.739, respectively, while the corresponding predictive r(2) values for the
      global minima-based CoMFA and CoMSIA models were 0.654 and 0.635, respectively.
      3D contour maps generated from these models provide the regions in space where
      interactive fields may influence the activity. The superimposition of contour
      maps on the active site of HIV-1 reverse transcriptase additionally helped in
      understanding the structural requirements of these inhibitors. The results
      provide insight for predictive and diagnostic aspects of this class of HIV-1 RT
      inhibitors for better activity.

PMID- 19117781
TI  - IGF-I replacement therapy in children with congenital IGF-I deficiency (Laron
      syndrome) maintains heart dimension and function.
AB  - OBJECTIVE: Untreated patients with congenital growth hormone deficiency (GHD) and
      IGF-I deficiency are characterized not only by dwarfism but also by acromicria
      and organomicria, such as the heart. We assessed cardiac dimensions and function
      in very young patients with Laron syndrome (LS) undergoing IGF-I replacement
      therapy. DESIGN: Two to seven echocardiographic measurements were performed
      during IGF-I replacement therapy on male (n=4) and female (n=4) LS -patients,
      mean+/-SD age of 7.1+/-3.6 years (range 1.6-11.6 years), weight 16.1+/-9.7 kg,
      and height 89.9+/-18.5 cm. As aged- and gender-matched controls served 44 healthy
      children, age: 8.7+/-5.5 years, weight: 36.1+/-22.4 kg, and height: 129.7+/
      33.1cm. Data of LS patients were normalized to body surface area and compared to
      the control group as well as nomograms of normal echocardiographic parameters for
      this age group. RESULTS: Left ventricular diastolic and systolic dimensions
      (LVDD/ LVSD, mm) and LV mass (gr) were significantly smaller in boys and girls
      with IGF-I treated LS compared with controls while the shortening fraction (%)
      and intraventricular septum thickness (mm) were similar. When compared with
      standard values for this age group, all treated LS patients were within 1
      standard deviation of the mean. CONCLUSION: IGF-I therapy of young patients with
      Laron syndrome maintain LV dimensions and function within the normal range of
      aged-matched controls.

PMID- 19117782
TI  - Immunological diagnosis of human angiostrongyliasis due to Angiostrongylus
      cantonensis (Nematoda: Angiostrongylidae).
AB  - Angiostrongylus cantonensis-associated eosinophilic meningitis in humans has been
      commonly reported worldwide. However parasitologically confirmed cases are not
      common, as the parasite has been recovered only infrequently from the
      cerebrospinal fluid of patients. The potential value of immunodiagnosis is
      therefore self-evident. Immunological tests can also help in the differential
      diagnosis of parasitic (particularly helminths) infections that cause
      eosinophilic meningitis. This paper summarizes the state of and advances in the
      immunological diagnosis of human angiostrongyliasis due to Angiostrongylus (=
      Parastrongylus) cantonensis. A specific antigen is available for the definitive
      diagnosis and unequivocal differentiation of eosinophilic meningitis due to
      helminth infections. Rapid diagnostic kits based on dot-blot ELISA have been
      developed and have proved to be simple, effective, and economical for field use.

PMID- 19117783
TI  - [Combined fracture of the distal radius and scaphoid in children. Report of two
      cases].
AB  - The authors report two cases of concomitant scaphoid and distal radial fractures,
      a rare combination of lesions in children. The first case was in a 14-year-old
      boy who presented a midscaphoid fracture associated with a distal forearm
      fracture. The second case concerned a 13-year-old boy who presented a midscaphoid
      fracture associated with a Salter type II distal radial fracture. Both fractures
      were reduced under general anaesthesia. The total period of immobilisation was 3
      months, using a large arm thumb cast. Associated scaphoid fractures should be
      suspected with all types of distal forearm injuries in children. Reduction of the
      radius fracture should be done carefully to avoid possible displacement of the
      scaphoid fracture.

PMID- 19117784
TI  - [Against systematic lombo-aortic lymphadenectomy in endometrial cancer].

PMID- 19117785
TI  - [Urinary incontinence, should fertile women undergo surgical procedure?].
AB  - The goal of this study was to make a Medline research about pregnancies which
      occur after surgical procedures for stress urinary incontinence (SUI). Therefore,
      we do not know the recurrence rate of SUI after pregnancy and the influence of
      the way of delivery on the risk of recurrence. We do not know either if we should
      apply a surgical procedure on women who have not achieved their pregnancies. In
      1998, a questionnaire based survey conducted in the USA showed a lower risk of
      recurrence after a caesarean section than after a vaginal delivery (p=0,03) when
      women had previously colposuspension or sling procedures. We found ten case
      reports and a French national survey (2006) about pregnancies after TOT or TVT
      procedure. No complication related to the tape was described during pregnancy.
      The recurrence rate along the pregnancy is about 15%, and the global recurrence
      rate (during pregnancy and after the childbirth) is about 20%. As a conclusion,
      pregnancy itself has an influence, and vaginal delivery seams to increase the
      risk of recurrence after the birth compare to the c-section. However this
      recurrence rate and these data do not appear enough to us to refuse a surgical
      treatment for women who have not completed their pregnancies and who suffer from
      UI without efficacy of physiotherapy. We do not have objective data to assess the
      best way of delivery. Further and large studies are needed although they are
      difficult to be carried through.

PMID- 19117786
TI  - [Impact of infertility and assisted reproductive techniques on sexuality].
AB  - OBJECTIVE: We studied the impact of infertility and all the more Assisted
      Reproductive Techniques on marital relations and sexuality. MATERIAL AND METHOD:
      Our study is based on a questionnaire distributed in our centre and on a review
      of literature. RESULTS: Our inquest shows that both partners keep a good
      relationship in their couple and support each other. But, whereas pleasure during
      intercourse is little affected, many couples feel a reduction of their desires.
      DISCUSSION AND CONCLUSION: This diminution of sexual desires, also noted in
      literature, can be explained by medical requirements intrusive for intimacy and
      also by strategies settled by the couples themselves during intercourse in order
      to optimise the chance of pregnancy. Medical staffs should take into
      consideration eventual sexual difficulties of the couples. Making them aware that
      their intimate life must remain or become again an end in itself, and not only a
      way of procreation, often permits a beneficial change of behaviour.

PMID- 19117787
TI  - [Radioguided occult lesion localization in breast cancer (ROLL): new
      techniques?].
AB  - Radioguided occult lesion localisation (ROLL) is a new technique which allows
      identification of non palpable breast lesion in breast cancer using, on the model
      of sentinel node procedure, injection of a radiotracer over the tumour lesion.
      With a gamma detection probe, it is then possible during surgery to identify in
      the same time the lesion and the sentinel lymph nodes. Compared with the wire
      guided localisation (WGL), ROLL seems easier to achieve for radiologists, the
      excision procedure seems to be simpler with a good lesions resection in sano rate
      and a good cosmetic result.

PMID- 19117788
TI  - Robust automatic detection and removal of fiducial projections in fluoroscopy
      images: an integrated solution.
AB  - Automatic detection and removal of fiducial projections in fluoroscopy images is
      an essential prerequisite for C-arm calibration. This paper presents an
      integrated solution to fulfill this task. A custom-designed calibration cage with
      a two-plane pattern of fiducials is utilized in our solution. The cage is
      attached to the C-arm image intensifier and acquired images are calibrated
      automatically by a three-step on-line calibration algorithm including fiducial
      projection detection, image calibration, and fiducial projection removal. A
      sequence of carefully designed image processing operations consisting of image
      binarization, connected-component labeling, region classification, adaptive
      template matching, and shape analysis, are developed for an accurate and robust
      localization of fiducial projections. A similarity measure that is proposed
      previously for image-based 2D-3D registration is employed in the adaptive
      template matching to improve the detection accuracy. Shape analysis based on the
      design information of the calibration cage is used to further improve the
      robustness of the detection. Thin-plate spline based vector transforms are used
      to correct the image distortion. The detected fiducial projections are then
      removed by an image inpainting technique based on the fast marching method for
      level set applications. Our in vitro experiments show on average 4s execution
      time on a Pentium IV machine, a zero false-detection rate, a miss-detection rate
      of 1.6+/-2.3%, and a sub-pixel localization error. Using a custom-made tool for
      checking accuracy, a forward projection error of 1.0+/-0.4 pixels and a backward
      projection error of 0.3+/-0.1 mm were found. We are confident that our solution
      is fast, robust, and accurate enough for image-guided interventional
      applications.

PMID- 19117789
TI  - Comparison of cage application modality in posterior lumbar interbody fusion with
      posterior instrumentation--a finite element study.
AB  - BACKGROUND: Posterior lumbar interbody fusion (PLIF) cages have achieved
      satisfactory fusion results, but cases of cage migration or mechanical failure
      were repeatedly reported. Therefore, we conducted a finite element study to
      determine the impact of cage applications including number, positioning, and
      adding posterior instrumentation (PI). METHODS: A finite element model of the
      lumbar spine was generated from Computer Tomography scans and was validated.
      Partial laminectomy, diskectomy with partial facetectomy, and single or double
      cage insertion were simulated onto the model, with or without posterior pedicle
      screws instrumentation. The maximal von Mises stresses between different loading
      conditions were compared between modalities to evaluate the risks of migration or
      mechanical failure. RESULTS: Posterior instrumentation decreases at least half
      the distortion stress of cage-endplate interface and facet joints, and diminishes
      the differences between the stresses of inserting one or two cages. Based on one
      cage insertion, adding posterior instrumentation provides more efficient
      stability than an additional cage. Furthermore, an obliquely inserted cage with
      posterior instrumentation produced lower stress than a cage inserted on one side
      due to better structural symmetry. Conclusively, one oblique anterior cage and
      bilateral posterior pedicle screws reconstructed the tripod system as the intact
      disc and facet joints, and provided similar stability as two cages did.

PMID- 19117790
TI  - Finite element analysis of side branch access during bifurcation stenting.
AB  - Stent implantation has become a widely accepted endovascular intervention for the
      treatment of stenosed arteries. This minimally invasive technique has shown
      excellent results in unbranched arteries. However, stenting bifurcation lesions
      remains a challenge in coronary intervention as it is associated with a lower
      success rate. Many different techniques have been proposed in medical practice
      but all the suggested methodologies have specific limitations. Numerical
      simulations may help to understand and eliminate the shortcomings of current
      clinical techniques and devices. In this study, one of the currently applied
      techniques is analysed which involves the implantation of a stent in the main
      branch, followed by subsequent inflation of a balloon through the side of the
      stent. This improves the side branch patency and provides access to the side
      branch for later stent implantations. The impact of using different balloon sizes
      and stent designs was investigated. The stent cell through which the balloon is
      inflated increases considerably and as intuitively expected, using a larger
      balloon results in a larger opening. Furthermore, it was observed that this
      procedure may compromise the downstream main branch lumen. These observations
      correspond well with previously reported results, which were based on in vitro
      studies. The added value of the proposed numerical model is the ability to study
      many different techniques/stents, without the need for various expensive stent
      samples.

PMID- 19117791
TI  - Virtual optimization of self-expandable braided wire stents.
AB  - At present, the deployment of self-expandable braided stents has become a common
      and widely used minimally invasive treatment for stenotic lesions in the
      cardiovascular, gastrointestinal and respiratory system. To improve these
      revascularization procedures (e.g. increase the positioning accuracy) the optimal
      strategy lies in the further development of the stent design. In the context of
      optimizing braided stent designs, computational models can provide an excellent
      research tool complementary to analytical models. In this study, a finite element
      based modelling strategy is proposed to investigate and optimize the mechanics of
      braided stents. First a geometrical and finite element model of a braided Urolume
      endoprosthesis was built with the open source pyFormex design tool. The results
      of the reference simulation of the Urolume stent are in close agreement with both
      analytical and experimental data. Subsequently, a simplex-based design
      optimization algorithm automatically adjusts the reference Urolume geometry to
      facilitate precise positioning by reducing the foreshortening with 20% while
      maintaining the radial stiffness. Therefore, the proposed modelling strategy
      appears to be a promising optimization methodology in braided stent design.

PMID- 19117792
TI  - The buffering effects of ethnic density on experienced racism and health.
AB  - Studies in the United Kingdom (UK) show a consistent inequality between the
      health of ethnic minorities and that of white people. This is exacerbated by the
      over-representation of ethnic minorities in deprived areas, which have been
      associated with poorer infant and child health, chronic disease, and high
      mortality rates. Ethnic density, defined as the proportion of ethnic minority
      residents in an area, is generally thought of in relation to the negative impacts
      of area effects on health. However, it can be considered in terms of social
      networks and supportive communities, possibly mitigating the detrimental impact
      of racism on the health of ethnic minority people. This study investigated the
      ethnic density effect and hypothesised that ethnic minority people who live in
      areas of high ethnic density would report decreased experienced racism and better
      health outcomes compared to their counterparts living in areas of low ethnic
      density. Multiple logistic regressions were conducted using data from the Fourth
      National Survey of Ethnic Minorities and the 1991 UK Census. Results showed a
      negative association between ethnic density and psychotic symptomatology, but no
      evidence of an association between ethnic density and general self-rated health.
      Findings confirm that the experience of racism is lower in places of higher
      ethnic density and indicate a tendency for a weaker association between racism
      and health as ethnic density increases.

PMID- 19117793
TI  - Functional genomics of root growth and development in Arabidopsis.
AB  - Roots are vital for the uptake of water and nutrients, and for anchorage in the
      soil. They are highly plastic, able to adapt developmentally and physiologically
      to changing environmental conditions. Understanding the molecular mechanisms
      behind this growth and development requires knowledge of root transcriptomics,
      proteomics, and metabolomics. Genomics approaches, including the recent
      publication of a root expression map, root proteome, and environment-specific
      root expression studies, are uncovering complex transcriptional and post
      transcriptional networks underlying root development. The challenge is in further
      capitalizing on the information in these datasets to understand the fundamental
      principles of root growth and development. In this review, we highlight progress
      researchers have made toward this goal.

PMID- 19117794
TI  - Micelle-enhanced and terbium-sensitized spectrofluorimetric determination of
      gatifloxacin and its interaction mechanism.
AB  - A terbium-sensitized spectrofluorimetric method using an anionic surfactant,
      sodium dodecyl benzene sulfonate (SDBS), was developed for the determination of
      gatifloxacin (GFLX). A coordination complex system of GFLX-Tb(3+)-SDBS was
      studied. It was found that SDBS significantly enhanced the fluorescence intensity
      of the complex (about 11-fold). Optimal experimental conditions were determined
      as follows: excitation and emission wavelengths of 331 and 547nm, pH 7.0, 2.0x10(
      4)moll(-1) terbium (III), and 2.0x10(-4)moll(-1) SDBS. The enhanced fluorescence
      intensity of the system (DeltaI(f)) showed a good linear relationship with the
      concentration of GFLX over the range of 5.0x10(-10) to 5.0x10(-8)moll(-1) with a
      correlation coefficient of 0.9996. The detection limit (3sigma) was determined as
      6.0x10(-11)moll(-1). This method has been successfully applied to the
      determination of GFLX in pharmaceuticals and human urine/serum samples. Compared
      with most of other methods reported, the rapid and simple procedure proposed in
      the text offers higher sensitivity, wider linear range, and better stability. The
      interaction mechanism of the system is also studied by the research of
      ultraviolet absorption spectra, surface tension, solution polarity and
      fluorescence polarization.

PMID- 19117795
TI  - Estimation of firing temperature of some archaeological pottery shreds excavated
      recently in Tamilnadu, India.
AB  - An attempt has been made in the present work to estimate the firing temperature
      of the archaeological pottery shreds excavated from the three archaeological
      sites namely Maligaimedu, Thiruverkadu and Palur in the state of Tamilnadu in
      INDIA. The lower limit of firing temperature of the Archaeological pottery shreds
      were estimated by refiring the samples to different temperatures and recording
      the corresponding FT-IR spectrum. The firing methods and conditions of firing
      were inferred from the characteristic absorption positions and the bands observed
      due to the presence of magnetite and hematite in the samples. In addition, the
      Scanning Electron Microscopic analysis were carried out to study the internal
      morphology, vitrification factor and the upper limit of the firing temperature of
      the potteries fired at the time of manufacture.

PMID- 19117796
TI  - Raman and micro-thermometric investigation of the fluid inclusions in quartz in a
      gold-rich formation from Lepaguare mining district (Honduras, Central America).
AB  - Fluid inclusions in the quartz crystals present in gold-rich veins from central
      Honduras have been studied by means of micro-thermometry and micro-Raman
      spectroscopy in order to provide information on the physico-chemical conditions
      and chemical composition of the mineralizing fluids. The use of a confocal micro
      Raman apparatus allowed to obtain information on the fluid composition, in
      particular on the gas phase, minimizing the contributions of the host matrix to
      the Raman signal. The samples studied were collected from an area (Lepaguare
      mining district, Northern-Central Honduras) rich in ore deposits due to the
      Cenozoic magmatic activity, where the gold and sulphide mineralization is
      connected with a system of quartz veins (few decimetres thick) occurring in low
      grade metamorphic rocks and produced by hydrothermal fluids. The quartz crystals
      present in the gold-rich veins often contain fluid inclusions. Four types of
      fluid inclusions have been observed, but their assemblage in the same clusters
      and fracture systems, as well as their comparable salinity and homogenization
      data, suggest that they have the same origin. Micro-thermometry and Raman
      spectroscopy provide a composition of the mineralizing fluids attributable to the
      system H(2)O-NaCl-KCl-CO(2)-CH(4), with temperature and pressure intervals of 210
      413 degrees C and 1050-3850 bar, respectively. These data agree with an
      epigenetic origin of the gold deposit (depth < 6 km) related to granitoid or
      granodiorite intrusions associated to orogenic environments.

PMID- 19117797
TI  - Synthesis and spectral investigations of mononuclear [N(6)], [N(8)] and dinuclear
      [N(10)] complexes of polyamide macrocycles: (57)Fe Mossbauer parameters of
      Fe(III) complexes.
AB  - New stable Fe(III) complexes of tetraamide [N(6)], [N(8)] and [N(10)] macrocyclic
      ligands are reported. One of them, [N(10)] is dinucleating, with two Fe(III)
      nuclei in the macrocyclic cavities. The structural features have been discussed
      on the basis of analytical, ESI mass, FT-IR, electronic, (1)H and (13)C NMR
      spectral studies. Magnetic moment studies indicate presence of anti
      ferromagnetically coupled (Fe(3+)-Fe(3+)=S(5/2)-S(5/2)) spin-spin interactions in
      the dinuclear [N(10)] complex. (57)Fe Mossbauer measurements confirm Fe(+/-3/2-
      >+/-1/2) nuclear transitions supporting high-spin configuration of Fe(III) nuclei
      with the presence of Kramer's double degeneracy.

PMID- 19117798
TI  - Tensions associated with the use of electronic knowledge resources within
      clinical decision-making processes: a multiple case study.
AB  - CONTENT AND OBJECTIVE: Health professionals now routinely use electronic
      knowledge resources (EKRs). Few studies have considered EKR-related tensions
      which may arise in a clinical decision-making context. The present study aims to
      explore three types of tension: (1) user-computer tension, (2) social tensions,
      and (3) organizational tensions (constraints associated with organizational
      routines and health policies). DESIGN, PARTICIPANTS, INTERVENTION, SETTING: We
      conducted a multiple case study, examining Family Medicine residents' searches
      for information in everyday life. Cases were defined as critical searches for
      information among 17 first year family medicine residents using InfoRetriever
      2003/2004 on a PDA over 1.5 months at McGill University. InfoRetriever-derived
      information was used within a resident-patient decision-making context in 84 of
      156 cases. For each case, residents were interviewed, and extracts of interview
      transcripts were assigned to themes using specialized software (presence of
      tension; type of tension). Further computer-assisted lexical-semantic analysis
      was performed on transcripts. Authors reached consensus on assignments. RESULTS:
      Twenty-five cases with tension were identified (one case had two types of
      tension), and illustrate the above mentioned types of tensions: (T1) tension
      between the resident and InfoRetriever (N=16); (T2) InfoRetriever-related tension
      between the resident and other social actors, specifically supervisors, other
      health care professionals and patients (N=7); (T3) InfoRetriever-related tension
      between the resident and the health organization/system (N=3). CONCLUSIONS:
      Results suggest EKR usage in a clinical decision-making context may have negative
      consequences when three types of tension arise in a clinical decision-making
      context. Illustrated types of tension are interrelated and not mutually
      exclusive. Awareness of EKR-related tensions may help clinicians to integrate
      EKRs in practice.

PMID- 19117799
TI  - Oropouche fever epidemic in Northern Brazil: epidemiology and molecular
      characterization of isolates.
AB  - BACKGROUND: Oropouche fever virus is an important arbovirus associated with
      febrile disease that re-emerged in 2006 in several municipalities of Para State,
      Bragantina region, Amazon, Brazil, 26 years after the last epidemic. OBJECTIVE:
      To investigate an Oropouche fever outbreak in this region. STUDY DESIGN: A
      serologic survey and prospective study of acute febrile cases were performed in
      Magalhaes Barata (urban and rural areas) and Maracana (rural area)
      municipalities. Serology (IgM-ELISA and hemagglutination-inhibition [HI]), virus
      isolation, RT-PCR and real-time-PCR were used to confirm Oropouche virus (OROV)
      as responsible for the febrile outbreaks. RESULTS: Real-time-PCR showed high
      titers of OROV in acute-phase serum samples from febrile patients. From 113 of
      119 acutely febrile patients with paired serum samples, OROV infections was
      confirmed by serologic conversion (n=76) or high titers (n=37) for both HI and
      IgM-ELISA. Patients had a febrile disease characterized by headache, chills,
      dizziness, photophobia, myalgia, nausea, and vomiting. Females and children under
      15 years of age were most affected. Nucleotide sequencing of six OROV isolates
      identified that genotype II was associated with the human disease epidemic.
      CONCLUSIONS: Oropouche fever, which has re-emerged in the Bragantina region in
      eastern Amazon 26 years after the last epidemic, is caused by genotype II, a
      lineage previously found only in Peru and western Brazil.

PMID- 19117800
TI  - Transposition of the great arteries, interrupted inferior vena cava and
      intestinal atresia: a new association?
AB  - We present a neonate with transposition of the great arteries, ventricular septal
      defect, inferior vena caval interruption with azygous continuation and intestinal
      atresia. This concurrence of anomalies has not been previously reported.

PMID- 19117801
TI  - Protocol based on thromboelastograph (TEG) out-performs physician preference
      using laboratory coagulation tests to guide blood replacement during and after
      cardiac surgery: a pilot study.
AB  - BACKGROUND: Allogenic blood transfusion may affect clinical outcomes negatively.
      Up to 20% of blood transfusions in the United States are associated with cardiac
      surgery and so strategies to conserve usage are of importance. This study
      compares administration according to physician's choice based on laboratory
      coagulation tests with application of a strict protocol based on the
      thromboelastograph (TEG). METHODS: Sixty-nine patients presenting for cardiac
      surgery were randomised to either study or control groups. In the study group a
      strict protocol was followed covering usage of all blood products according to
      TEG patterns. In the control group, the physician directed product administration
      with reference to activated partial thromboplastin time (APTT), international
      normalised ratio (INR), fibrinogen and platelet count. Bleeding, re-sternotomy,
      minimum haemoglobin, intubation time, and ICU stay were documented. RESULTS: TEG
      based management reduced total product usage by 58.8% in the study group but this
      was not statistically significant. This was associated with a statistically
      insignificant trend towards better short-term outcomes. CONCLUSIONS: This pilot
      study suggests that a strict protocol for blood product replacement based on the
      TEG might be highly effective in reducing usage without impairing short-term
      outcome.

PMID- 19117802
TI  - Left anterior descending artery endarterectomy by hydrodissection.
AB  - Complete revascularisation of a diffusely diseased left anterior descending (LAD)
      coronary artery is best done by endarterectomy in conjunction with coronary
      artery bypass grafting. We describe a simple, effective, and safe technique of
      performing LAD endarterectomy by hydrodissection.

PMID- 19117803
TI  - Efficacy of high-flow dialysate continuous hemodiafiltration in the treatment of
      fulminant hepatic failure.
AB  - We compared the clinical efficacy of high-flow dialysate continuous
      hemodiafiltration (HFCHDF) performed as artificial liver support (ALS) in
      fulminant hepatic failure (FHF) with those of conventional ALS techniques. Ninety
      patients were divided into non-HFCHDF and HFCHDF groups. Rate of recovery from
      coma was significantly higher in the HFCHDF group (70.2%) than in the non-HFCHDF
      group (44.2%) (p<0.01). The excellent recovery rate from coma achieved in
      patients with FHF by HFCHDF may be due to its enhanced capacity for liver support
      enabling efficient removal of substances causing hepatic coma from blood. HFCHDF
      should thus be useful for ALS.

PMID- 19117804
TI  - Histological evaluation of an alternative method of neophalloplasty based on two
      lower abdominal skin flaps and simultaneous buccal mucosa graft in the ventral
      surface of the neophallus (two-stage urethroplasty): experimental study in
      rabbits.
AB  - OBJECTIVE: To evaluate, in an experimental study in rabbits, a new model of
      neophalloplasty based on two lower abdominal skin flaps and ventral buccal mucosa
      graft for planned two-stage urethroplasty procedure. MATERIAL AND METHODS:
      Sixteen rabbits were operated and divided into four equal groups which were
      sacrificed at 2, 4, 8 and 12 weeks. The inflammatory pattern, presence of sub
      epithelial fibrosis and epithelial changes in the grafted area were evaluated
      histologically. RESULTS: There were no deaths and no dehiscence of the wound was
      seen. One animal in the 2-week group developed an ulcer in the grafted area. We
      found minimal contracture of the neophallus, but this was not statistically
      significant between groups. Buccal mucosa graft showed good uptake in all groups,
      with vascular support from subcutaneous tissue of the flaps. The grafted area
      developed epithelial metaplasia, showing a decrease in cell layers with time,
      with disappearance of the sub-epithelial papillae and appearance of stratum
      granulosum and keratinization of the epithelial graft surface. A decrease in sub
      epithelial fibrosis with replacement of immature by mature (eosinophilic)
      collagen was found. In the later groups was also observed an important decrease
      in inflammatory response, and the chorion of the grafted area presented a dilated
      capillary network, indicating that the process of neoangiogenesis was effective.
      CONCLUSION: Buccal mucosa displayed histological integration in the abdominal
      flaps with epithelial metaplasia in all groups. The surgical aspect of the
      neophallus was cosmetically acceptable, with minimal contracture.

PMID- 19117805
TI  - This is the reason why we are exploring the possibility of rewarding courageous
      contributors and reviewers by giving them CME points for their hard work.

PMID- 19117806
TI  - Miniaturized hollow fiber assisted liquid-phase microextraction and gas
      chromatography-mass spectrometry for the measurement of progesterone in human
      serum.
AB  - Miniaturized hollow fiber assisted liquid-phase microextraction (HF-LPME) and gas
      chromatography-mass spectrometry (GC-MS) for the determination of progesterone in
      human serum sample is described. The detection limit and the quantification limit
      of progesterone in human serum sample are 0.5 and 2 ng mL(-1) (ppb),
      respectively. The calibration curve for progesterone is linear with a correlation
      coefficient of >0.999 in the range of 2-500 ng mL(-1). The average recoveries of
      progesterone in human serum samples spiked with 5, 50 and 200 ng mL(-1)
      progesterone are 97.4% (R.S.D.: 9.3%), 100.3% (R.S.D.: 4.7%) and 99.8% (R.S.D.:
      3.4%), respectively. This simple, accurate, sensitive and selective analytical
      method can be applicable for the determination of progesterone in human serum
      samples.

PMID- 19117807
TI  - Online capillary solid phase extraction and liquid chromatographic separation
      with quantitative tandem mass spectrometric detection (SPE-LC-MS/MS) of
      ximelagatran and its metabolites in a complex matrix.
AB  - This work presents the development and validation of a fully automated
      quantitative analysis method of melagatran, its prodrug ximelagatran, and its
      major metabolites for the study of drug behavior in biofluids. The method
      involves online sample clean-up and enrichment on a C(4) capillary column
      followed by separation on a capillary C(18) column. Electrospray ionization
      tandem mass spectrometric detection in positive ion mode was performed with
      multiple reactions monitoring of eight different transients, divided into two
      time segments with four transients each. The structural similarity, the
      complexity of the matrix (pig liver extract) and the formation of isobaric
      fragment ions, made efficient chromatographic separation necessary. The analysis
      method provides valid accuracy (<9%; RSD%), precision (<8%; RSD%), linearity
      (<1.2 nM-1 microM; R(2)>0.999), limit of quantitation (<3.6 nM), retention
      repeatability (<1.2%; RSD%), selectivity, as well as analyte and column
      stabilities over a wide concentration range.

PMID- 19117808
TI  - Determination of kanamycin A, amikacin and tobramycin residues in milk by
      capillary zone electrophoresis with post-column derivatization and laser-induced
      fluorescence detection.
AB  - An analytical method for kanamycin A, amikacin and tobramycin of aminoglycoside
      (AG) antibiotics in milk samples was proposed using capillary zone
      electrophoresis (CZE) with post-column derivatization and laser-induced
      fluorescence detection. A simple and convenient homemade coaxial-gap reactor was
      adopted in the post-column derivatization of the AGs with 1.0 mmol/L naphthalene
      2,3-dicarboxaldehyde and 8.0 mmol/L 2-mercaptoethanol in 35 mmol/L sodium
      tetraborate buffer (pH 10.0) of 30% (v/v) methanol. 50 mmol/L sodium acetate (pH
      5.0) containing 0.5 mmol/L cetyltrimethyl ammonium bromide was used as the
      separation buffer. The linear calibration concentrations and detection limits
      were from 2.1 x 10(-5) to 5.0 x 10(-2)g/L and in the range of 7 x 10(-6) to 2 x
      10(-5)g/L, respectively. The recoveries of the AGs in milk samples were from 81.6
      to 93.1% (n=3).

PMID- 19117809
TI  - Miniaturized hollow fiber assisted liquid-phase microextraction and gas
      chromatography-mass spectrometry for determination of benzophenone and derivates
      in human urine sample.
AB  - The determination of benzophenones (BPs) in human urine sample by miniaturized
      hollow fiber assisted liquid-phase microextraction (HF-LPME) and gas
      chromatography-mass spectrometry (GC-MS) is described. As analytes, BP, its
      metabolites benzhydrol (BP-OH) and 2-hydroxybenzophenone (2OH-BP), and its
      derivatives 2-hydroxy-4-methoxybenzophenone (BP-3) and 2-hydroxy-4-methoxy-4'
      methylbenzophenone (BP-10) were selected. The detection limit and the
      quantification limit of BPs in human urine sample are 5-10 and 20-50 pg mL(-1),
      respectively. The calibration curve for BPs is linear with correlation
      coefficient higher than 0.99 in the range of 0.02-10 or 0.05-10 ng mL(-1). The
      average recoveries of BPs in human urine samples spiked with 0.5 and 5 ng mL(-1)
      BPs are 89.8-100.2% (RSD: 2.5-9.3%) and 89.3-99.9% (RSD: 2.9-3.7%), respectively.
      Ten human urine samples were analyzed using the present method. BP-OH and BP-3
      were detected in all the samples within the range of 0.24-5.91 and 0.43-5.17 ng
      mL(-1), respectively. This simple, sensitive, and selective analytical method was
      successfully applied to the determination of trace amounts of BPs in human urine
      samples.

PMID- 19117810
TI  - Performance of polymeric materials for solid phase extraction prior to
      chromatographic analysis.
AB  - Synthetic polymeric materials such as polyethylene and polyurethane (PU) were
      compared to conventional adsorbents for solid phase extraction for cleaning up
      biological samples. Efficiency in eliminating proteins and other components
      usually present in biological samples, such as serum, urine, and tissues
      extracts, was evaluated. The assays consisted of measuring the remaining protein
      content in serum and tissue homogenates (liver) and collecting the spectra in the
      UV region for urine samples. Since the analysis of many endogenous and exogenous
      species in these matrices usually involves chromatographic separation, the
      efficiency of the clean-up procedures was also evaluated by injecting cleaned
      samples into a C-18 chromatographic column with UV detection. Among the
      investigated polymers, polytetrafluorethylene, high density polyethylene (HDPE)
      and ultra-high molecular weight polyethylene (UHMWPE) presented the best
      performance in retaining serum proteins. Proteic components of the liver
      homogenate were completely retained on polyurethane and polybutadiene (PB). Urine
      samples were cleaned by crossing columns of polytetrafluorethylene, ultra-high
      molecular weight polyethylene, high density polyethylene, polyurethane, and
      polyethylene co-butyl acrylate co-anhydride maleic (PEco), since the spectra
      collected after column percolation presented no peaks in the region between 190
      and 390 nm. SPE cartridges showed different behavior, but along the lines of
      their usual performance; neither serum proteins nor urine components were
      retained on the phases and the liver components, though partially retained, were
      not desorbed with either water or methanol washes, with the exception of SAX.
      Chromatograms of samples cleaned with high density polyethylene showed that
      polymeric materials can be satisfactorily used as adsorbent for biological matrix
      components.

PMID- 19117811
TI  - Electrophoresis and liquid chromatography/tandem mass spectrometry in disease
      biomarker discovery.
AB  - The search for disease markers is not new; however, with the emergence of new
      technologies such as nano-HPLC and electrospray ionization and time of flight
      mass spectrometry, the search has intensified considerably. Genomic, proteomic
      and metabolomic technologies are being used to search for novel disease markers.
      In this manuscript emphasis will be on different HPLC and MS methods that are
      used to search for metabolites and proteins that can be used for the discovery of
      novel, sensitive and specific disease biomarkers. Definitions of terms such as
      sensitivity, specificity, and protein profiles will be given. Methods used for
      effective fractionation, separation and quantitation of proteins and peptides
      using HPLC/MS will be discussed and examples are presented. A brief discussion of
      electrophoretic procedures used for protein fractionation and biomarker discovery
      is also included.

PMID- 19117812
TI  - Liquid chromatography-tandem mass spectrometric assay for sorafenib and sorafenib
      glucuronide in mouse plasma and liver homogenate and identification of the
      glucuronide metabolite.
AB  - The first bioanalytical assay for the simultaneous determination of sorafenib and
      sorafenib-glucuronide in mouse plasma and liver homogenate was developed and
      validated. In addition, the structure of the glucuronide metabolite was
      elucidated. The quantitative assay started with addition of isotopically labeled
      internal standards to a 20 microl sample volume and protein precipitation with
      acetonitrile, the supernatant was diluted with water and injected into the
      chromatographic system. A polar embedded reversed-phase column with gradient
      elution using formic acid in water-acetonitrile was used. The eluate was
      transferred into an electrospray interface with positive ionization and the
      analytes were detected and quantified using triple quadrupole mass spectrometry.
      The assay was validated in the ranges 10-5000 ng/ml for sorafenib and 1-500 ng/ml
      for sorafenib-glucuronide, the lowest levels of these ranges (10 and 1 ng/ml)
      being the lower limits of quantification (LLQ). Within day precisions were 2-8%,
      between day precisions 2-10% (both excluded the LLQ level of the glucuronide) and
      accuracies were between 89% and 106%. Both analytes were chemically stable under
      all relevant conditions. The assay was successfully applied in pilot in vivo
      pharmacokinetic studies with sorafenib in mice.

PMID- 19117813
TI  - Validation and performance comparison of two carbon isotope ratio methods to
      control the misuse of androgens in humans.
AB  - Carbon isotope ratio of androgens in urine specimens is routinely determined to
      exclude an abuse of testosterone or testosterone prohormones by athletes.
      Increasing application of gas chromatography/combustion/isotope ratio mass
      spectrometry (GC/C/IRMS) in the last years for target and systematic
      investigations on samples has resulted in the demand for rapid sample throughput
      as well as high selectivity in the extraction process particularly in the case of
      conspicuous samples. For that purpose, we present herein the complimentary use of
      an SPE-based assay and an HPLC fractionation method as a two-stage strategy for
      the isolation of testosterone metabolites and endogenous reference compounds
      prior to GC/C/IRMS analyses. Assays validation demonstrated acceptable
      performance in terms of intermediate precision (range: 0.1-0.4 per thousand) and
      Bland-Altman analyses revealed no significant bias (0.2 per thousand). For
      further validation of this two-stage analyses strategy, all the specimens (n=124)
      collected during a major sport event were processed.

PMID- 19117814
TI  - Hepatitis B surface antibody purification with hepatitis B surface antibody
      imprinted poly(hydroxyethyl methacrylate-N-methacryloyl-L-tyrosine methyl ester)
      particles.
AB  - Hepatitis B surface antibody imprinted poly(hydroxyethyl methacrylate-N
      methacryloyl-L-tyrosine methyl ester) particles were prepared for the
      purification of hepatitis B surface antibody from human plasma. N-methacryloyl-L
      tyrosine methyl ester was chosen as a complexing agent for hepatitis B surface
      antibodies. Hepatitis B surface antibody imprinted poly(hydroxyethyl methacrylate
      N-methacryloyl-L-tyrosine methyl ester) particles were characterized by surface
      area measurements, swelling test, scanning electron microscopy, elemental
      analysis, and Fourier transform infrared spectroscopy. Ethylene glycol (1.0M) was
      used as desorption agent. Adsorption studies were performed from hepatitis B
      surface antibody and anti-hepatitis A antibody positive human plasma. Effects of
      antibody concentration, contact time, N-methacryloyl-L-tyrosine methyl ester
      content and temperature on the adsorption capacity were investigated. The amount
      of hepatitis B surface antibody adsorbed per unit mass increased with increasing
      hepatitis B surface antibody concentration, then reached saturation. Maximum
      hepatitis B surface antibody adsorption amount was 21.4 mIU/mg. Adsorption
      process reached the equilibrium in 60 min. Competitive adsorption of hepatitis B
      surface antibody, total anti-hepatitis A antibody and total immunoglobulin E was
      investigated for showing the selectivity. Hepatitis B surface antibody-imprinted
      particles could adsorb hepatitis B surface antibody 18.3 times more than anti
      hepatitis A antibody and 2.2 times more than immunoglobulin E. It can be
      concluded that hepatitis B surface antibody-imprinted particles have significant
      selectivity for hepatitis B surface antibody.

PMID- 19117815
TI  - Determination of a benzamide histone deacetylase inhibitor, MS-275, in human
      plasma by liquid chromatography with mass-spectrometric detection.
AB  - An analytical method was developed and validated for the quantitative
      determination of the histone deacetylase inhibitor MS-275 in human plasma.
      Calibration curves were linear in the concentration range of 1-250 ng/mL. Sample
      pretreatment involved a liquid-liquid extraction of 0.1 mL aliquots of plasma
      with methyl tert-butyl ether. MS-275 and the internal standard, benzanilide, were
      separated on a Zorbax SB-Phenyl column (4.6 mm x 75 mm I.D., 3.5 microm), using a
      mobile phase composed of methanol and 10 mM ammonium formate (pH 2.9). The column
      eluent was monitored by mass spectrometry with electrospray ionization. Accuracy
      and precision of three concentrations of quality control samples ranged from
      96.56 to 107.02% and 0.97 to 4.29%, respectively. This method represents an
      improvement over the previously published analytical assay for this agent,
      increasing the accuracy and precision (through addition of a suitable internal
      standard) and expanding the analytical range. The developed method was applied to
      study the pharmacokinetics of MS-275 in 724 clinical samples.

PMID- 19117816
TI  - Cassette analysis of eight beta-blockers in bovine eye sclera, choroid-RPE,
      retina, and vitreous by liquid chromatography-tandem mass spectrometry.
AB  - A simple, selective, and sensitive LC-MS/MS method was developed for the
      simultaneous extraction and determination of eight beta-blockers (atenolol,
      sotalol, nadolol, pindolol, timolol, metoprolol, betaxolol and propranolol) in
      various bovine eye tissues including sclera, choroid-RPE, retina, and vitreous.
      The analytes were extracted by liquid-liquid extraction after samples were
      alkalinized with 2% NaOH solution in water. The chromatographic separation was
      performed on a Hypersil-ODS C18 column (100 mm x 2.1 mm, 3.9 microm) using a
      gradient mixture of (A) 5 mM ammonium formate in water (pH 3.5 adjusted with
      formic acid) and (B) acetonitrile:methanol (75:25) containing 0.02% triethyl
      amine (pH 4.0; adjusted with formic acid) as mobile phase at a flow rate of 0.4
      ml/min. The compounds were ionized in the positive electrospray ionization (ESI)
      mode and detected in the multiple reaction monitoring (MRM) mode. The average
      recoveries in all four eye tissues for all beta-blockers were >82%, except for
      sotalol (>51%). The matrix effect for beta-blockers ranged from 81 to 110% in the
      four eye tissues. This analytical method was validated and applied successfully
      for simultaneous quantification of the beta-blockers in sclera after tissue
      exposure using cassette dosing method. The calibration curve was linear in the
      range of 10-2000 ng/ml for all analytes, with the correlation coefficient >0.996.
      Intra-day and inter-day precision (% CV) was less than 15%, and accuracy ranged
      from 85 to 110% for all analytes. Scleral uptake was the lowest for sotalol and
      atenolol, two hydrophilic beta-blockers, and the highest for propranolol, a
      lipophilic beta-blocker.

PMID- 19117817
TI  - High-density polyethylene facial implants show surface oxidation in SEM and EDX
      examination: a pilot study.
AB  - Previous histopathological studies on explanted Medpor high-density polyethylene
      (HDPE) facial implants indicated signs of material destruction and claimed to
      observe phagocytized HDPE particles within the tissue samples beside the usual
      type IV reaction with severe fibrosis. We examined new and explanted Medpor
      material with scanning electron microscopy (SEM) and energy-dispersive X-ray
      analysis (EDX). The implant surface of three patient-derived specimens showed
      significantly higher oxygenation in EDX analysis and morphological changes in SEM
      compared to the new unused material directly after opening of the package and
      after 1 year of exposure to air. Our preliminary findings indicate a possible
      oxidative biocorrosion in HDPE surgical implants. Further studies should confirm
      these pilot project results.

PMID- 19117818
TI  - Molecular dynamics simulations on the interaction between polymers and
      hydroxyapatite with and without coupling agents.
AB  - Molecular dynamics (MD) simulations were employed to study
      hydroxyapatite/biopolymer interface interactions in composites for biomedical
      applications. The study analyzed the binding energies between hydroxyapatite (HA)
      and three polymers: polyethylene (PE), polyamide (PA) and polylactic acid (PLA).
      The interactions of polymers on HA crystallographic planes (001), (100) and (110)
      were simulated. The effects of the silane coupling agent (A174) on interfacial
      binding energies were also examined. The results show that HA (110) has the
      highest binding energy with these polymers because of its higher planar atom
      density than that of HA (001) and (100). The binding energies of PA/HA and PLA/HA
      are much higher than that of PE/HA, which might be attributed to large number of
      polar groups in PA and PLA chains. The silane coupling agent A174 increases the
      binding energy between PE and HA, but not for the PA/HA and PLA/HA systems. The
      MD results can be used to guide the design of polymer/HA composites and to select
      proper coupling agents.

PMID- 19117819
TI  - Morphological control and assembly of zinc oxide using a biotemplate.
AB  - Zinc oxide is a wide band gap material that has significant applications in
      photovoltaics, piezoelectrics and optoelectronics. Traditionally, ZnO has been
      synthesized using high temperatures and harsh reaction conditions. Recently,
      benign reaction conditions have been used to synthesize ZnO using amine and
      citrate additives. In this study, peptide phage display was performed to identify
      a peptide, termed Z1, that binds to and directs the growth of ZnO hexagonal
      nanocrystals. By altering the concentration of Z1 peptide, the ZnO nanocrystal
      morphology can be tailored. Additionally, Z1 peptide was used to direct the
      growth of ZnO structures on free-standing silk films. The results presented here
      demonstrate the utility of peptides in controlling the structure and deposition
      of ZnO.

PMID- 19117820
TI  - Modular injectable matrices based on alginate solution/microsphere mixtures that
      gel in situ and co-deliver immunomodulatory factors.
AB  - Biocompatible polymer solutions that can crosslink in situ following injection to
      form stable hydrogels are of interest as depots for sustained delivery of
      therapeutic factors or cells, and as scaffolds for regenerative medicine. Here,
      injectable self-gelling alginate formulations obtained by mixing alginate
      microspheres (as calcium reservoirs) with soluble alginate solutions were
      characterized for potential use in immunotherapy. Rapid redistribution of calcium
      ions from microspheres into the surrounding alginate solution led to crosslinking
      and formation of stable hydrogels. The mechanical properties of the resulting
      gels correlated with the concentration of calcium-reservoir microspheres added to
      the solution. Soluble factors such as the cytokine interleukin-2 were readily
      incorporated into self-gelling alginate matrices by simply mixing them with the
      formulation prior to gelation. Using alginate microspheres as modular components,
      strategies for binding immunostimulatory CpG oligonucleotides onto the surface of
      microspheres were also demonstrated. When injected subcutaneously in the flanks
      of mice, self-gelling alginate formed soft macroporous gels supporting cellular
      infiltration and allowing ready access to microspheres carrying therapeutic
      factors embedded in the matrix. This in situ gelling formulation may thus be
      useful for stimulating immune cells at desired locales, such as solid tumors or
      infection sites, as well as for other soft tissue regeneration applications.

PMID- 19117821
TI  - Finite element analysis of a four-unit all-ceramic fixed partial denture.
AB  - All-ceramic restorations are known to be prone to brittle fracture. However, a
      previously performed in vitro study indicates that four-unit fixed partial
      dentures (FPDs) with a zirconia framework are sufficiently strong to withstand
      occlusal forces in the posterior region. The aim of this study was to determine
      the stress distribution in such a four-unit FPD made of yttria-stabilized
      polycrystalline tetragonal zirconia (Y-TZP), under an occlusal load. A three
      dimensional finite element model was constructed and a stress analysis performed
      with a force of 1630 N applied at the centre of the middle connector area. The
      location of maximum tensile stress according to finite element analysis coincided
      with the fracture origin of all 10 specimens fractured within the previous in
      vitro study. The maximum tensile stress in the area of the middle connector
      amounted to 633 MPa. It increased with the load being applied from the oral
      towards the buccal side (648 MPa) and decreased with the load being applied from
      the buccal towards the oral side (570 MPa). These stresses are of the same order
      as the flexural strength of Y-TZP, determined under standardized test conditions
      to be 600-1000 MPa. The model presented is intended to be used for further
      investigations, including thermally induced stresses during veneering.

PMID- 19117822
TI  - What is the learning curve for intraoperative neuromonitoring in thyroid surgery?
AB  - BACKGROUND: The study describes the initial experience and learning curve of
      intraoperative neuromonitoring (IONM) during thyroidectomy. We describe the
      prevalence and patterns of IONM technical problems. METHODS: Prospective series
      of 152 consecutive thyroid operations (304 nerves at risk) were analyzed.
      Standard technique consists of monitoring vagal and RLNs before, during and after
      resection. Personal gain of experience was defined by the preceding number of
      thyroid operations. To establish the number of thyroidectomies required before
      achieving an effective and safe IONM technique, all of the procedures were
      divided into three chronological groups of about 50 cases (groups 1, 2, and 3).
      RESULTS: Patients (90%) had successful IONM with initial endotracheal tube
      position. Fifteen patients (10%) needed further tube adjustment. Out of 15
      patients 14 (93%) were due to non-optimal contact of endotracheal surface
      electrodes to vocal cords. Tube malrotation was the main reason for initial
      failure (53%). The success rates of prompt IONM technique were 80% in group 1,
      92% in group 2, and 98% in group 3 (p<0.05). Mean operating time was low in group
      3 (p<0.03). Vagus and RLNs were localized and monitored in all the cases (100%).
      The incidence of temporary RLN injury was 2.6%. No permanent complications
      occurred. Negative EMG response indicated an altered function of RLN and stage
      thyroidectomies were scheduled. Transient RLN palsies were seen without changes
      during the entire study period. CONCLUSIONS: This is the first series of
      thyroidectomies with standardized IONM technique performed in Italy.
      Neuromonitoring was effective in providing identification and function of
      laryngeal nerves. IONM successful rates were affected considerably by the extent
      of surgical and anaesthesiological experiences, starting with relatively low
      rates in the beginner group and then increasing. We assessed the learning curve:
      improved operative variables and safe technique were seen in about 50 patients.

PMID- 19117823
TI  - Transplanted endothelial progenitor cells increase neo-vascularisation of rat pre
      fabricated flaps.
AB  - BACKGROUND: Flap pre-fabrication is dependent on the eventual re-vascularisation
      of the implanted vascular carrier and the presence of a desirable, donor-skin
      site. However, insufficient neo-vascularisation and subsequent necrosis is an
      obstacle for this technique. A recent discovery demonstrated that endothelial
      progenitor cells (EPCs) augment post-natal neo-vascularisation in ischaemic
      tissues. As a result, we examined whether transplantation of bone-marrow-derived
      EPCs (BM-EPCs) increases neo-vascularisation and augments the survival areas of
      pre-fabricated flap in a rat model. METHODS: Rat bone-marrow-derived mononuclear
      cells (BM-MNCs) were isolated by density gradient centrifugation and cultured in
      EGM-2MV. The EPCs derived from BM-MNCs were identified by surface makers such as
      CD34, KDR, CD133 and double-positive staining with 1,1'-dioctadecyl-3,3,3',3'
      tetramethylindocarbocyanine-labelled acetylated low-density lipoprotein (Dil-Ac
      LDL) and FITC-labelled Ulex europaeus agglutinin-1 (FITC-UEA-1). Pre-fabricated
      flaps were created by ligating the right femoral vascular pedicle and implanting
      it underneath the abdominal flap. Forty-five rats were randomly divided into
      three equal groups. The implantation site around the pedicle was injected
      subcutaneously with fluorescence-labelled BM-EPCs in group I (n=15), with
      vascular endothelium growth factor (VEGF) protein in group II (n=15) and with
      phosphate-buffered saline (PBS) in control group III. Four weeks after injection,
      the abdominal island flap was elevated and sutured back. Then, neo
      vascularisation and flap viability was evaluated on day 7. The labelled EPCs were
      examined by fluorescence microscopy. RESULTS: After 7 days of culture, the
      attached cells were spindle shaped and expressed CD34, KDR and CD133. These cells
      incorporated DiI-Ac-LDL and bound FITC-UEA-1. Greater augmentation of flap
      survival (87.26+/-10.13% vs. 66.13+/-9.9% and 55.59+/-13.06%, P<0.001), higher
      capillary density (38.67+/-9.52 capillaries per mm(2) vs. 25.83+/-6.34
      capillaries per mm(2) and 26.5+/-5.61 capillaries per mm(2), P<0.05) and larger
      vascular territories on the microangiogram were observed in the EPCs-treated
      group relative to the other two groups. The labelled cells formed new vessel
      structures and expressed von Willebrand factor (vWF) in the pre-fabricated flap.
      CONCLUSIONS: Local transplantation of BM-EPCs may be a useful strategy for
      increasing the survival of pre-fabricated flaps, which is consistent with
      'therapeutic vasculogenesis'. EPCs are superior to VEGF in their neo
      vascularisation ability.

PMID- 19117824
TI  - Self-esteem and personality in subjects with and without body dysmorphic disorder
      traits undergoing cosmetic rhinoplasty: preliminary data.
AB  - BACKGROUND: Many individuals with body dysmorphic disorder (BDD) seek non
      psychiatric treatment. BDD occurs in about 5% of patients who seek cosmetic
      surgery, and rhinoplasty is the most frequently sought treatment. A correlation
      exists between individuals' self-esteem and demand for cosmetic surgery.
      OBJECTIVE: To investigate whether those subjects with BDD traits requesting
      cosmetic rhinoplasty differ from those without BDD traits in self-esteem,
      personality and quality of life. METHODS: This study included 54 patients
      applying to the 1st ENT Division of Turin University. Assessment of the patients
      before cosmetic rhinoplasty includes: nasal obstruction symptom evaluation,
      health-related quality of life, Rosenberg self-esteem scale, body dysmorphic
      disorder questionnaire (BDDQ) and temperament and character inventory (TCI).
      Based on their responses to BDDQ questions 1, 3 and 4, patients were subdivided
      into subgroups and then compared. RESULTS: No difference emerged in the objective
      data. Lower self-esteem, higher harm avoidance (HA) and lower self-directedness
      (SD) are found in subjects who are worried about how they look, in those with
      interference in their social life due to this worry and in those who spend more
      than 3h per day thinking about the way they look. Novelty seeking (NS) is
      significantly higher in subjects who think about their looks for up to 3h than in
      those who spend less than 1h. CONCLUSION: Different subgroups of patients are
      identified. The first group includes pessimistic, shy, insecure subjects; people
      with fragile and immature personality and poor self-esteem; individuals concerned
      about the way they look and those who spend more time thinking about it. The
      second group includes more confident subjects with stronger personality and
      greater self-esteem. A third, less differentiated group, includes more impulsive
      (high NS) subjects who spend an intermediate amount of time thinking about the
      way they look. Patients should be carefully screened and assessed before cosmetic
      surgery interventions to avoid frustration to both, clinicians and patients.

PMID- 19117825
TI  - Is the foot elevation the optimal position for wound healing of a diabetic foot?
AB  - In managing diabetic foot ulcers, foot elevation has generally been recommended
      to reduce oedema and prevent other sequential problems. However, foot elevation
      may decrease tissue oxygenation of the foot more than the dependent position
      since the dependent position is known to increase blood flow within the arterial
      system. In addition, diabetic foot ulcers, which have peripheral vascular
      insufficiency, generally have less oedema than other wounds. Therefore, we argue
      that foot elevation may not be helpful for healing of vascularly compromised
      diabetic foot ulcers since adequate tissue oxygenation is an essential factor in
      diabetic wound healing. The purpose of this study was to evaluate the influence
      of foot height on tissue oxygenation and to determine the optimal foot position
      to accelerate wound healing of diabetic foot ulcers. This study included 122
      cases (73 males and 47 females; two males had bilateral disease) of diabetic foot
      ulcer patients aged 40-93 years. Trans-cutaneous partial oxygen tension (TcpO(2))
      values of diabetic feet were measured before and after foot elevation (n=21).
      Elevation was achieved by placing a foot over four cushions. We also measured
      foot TcpO(2) values before and after lowering the feet (n=122). Feet were lowered
      to the patient's tibial height, approximately 30-35 cm, beside a bed handrail.
      Due to the large number of lowering measurements, we divided them into five sub
      groups according to initial TcpO(2.) Tissue oxygenation values were compared.
      Foot-elevation-lowered TcpO(2) values before and after elevation were 32.5+/-22.2
      and 23.8+/-23.1 mmHg (p<0.01), respectively. Foot-lowering-augmented TcpO(2)
      values before and after lowering were 44.6+/-23.8 and 58.0+/-25.9 mmHg (p<0.01),
      respectively. The lower the initial TcpO(2) level, the more the TcpO(2) level
      increased. The foot lowering, rather than elevation, significantly augments
      TcpO(2) and may stimulate healing of diabetic foot ulcers.

PMID- 19117826
TI  - Autogenous digital artery graft for repair of digital nerve defects in emergency
      hand reconstruction: two-year follow-up.

PMID- 19117827
TI  - What do midwives need to understand/know about smoking in pregnancy?
AB  - AIM: This paper seeks to help midwives more fully understand smoking in
      pregnancy, particularly from a midwifery partnership perspective. METHOD: Using
      the midwifery philosophy of partnership as a framework for reviewing literature
      on smoking in pregnancy, we explored the literature on nicotine metabolism and
      addiction in general, and the changes that occur in pregnancy. Quit smoking
      interventions commonly used were examined to see if knowledge about addiction and
      the physiological adaptations of pregnancy are incorporated into anti-smoking
      efforts aimed at pregnant women. RESULTS: Quitting is harder for the pregnant
      woman because the physiological adaptations of pregnancy increase the clearance
      of nicotine thus lowering nicotine levels and increasing the desire to smoke.
      Women who continue to smoke generally have fewer external sources of pleasure and
      satisfaction in their lives, which, when combined with the physiological and
      emotional challenges of pregnancy, means that they are less likely to quit
      smoking and remain abstinent. These factors do not appear to be taken into
      account for pregnant smokers. The concept of partnership between women and
      midwives during anti-smoking interactions is lacking. CONCLUSION: Midwives are in
      a position to support women and their families in all health related issues,
      including smoking cessation. We recommend that midwives ask permission before
      making enquires about sensitive issues such as smoking. When discussing smoking
      with pregnant women, midwives work within the philosophy of midwifery, with the
      emphasis on building trust and maintaining relationships. Great sensitivity is
      required and as much as possible the conversation should be a dialogue, not a
      monologue.

PMID- 19117828
TI  - Rates and determinants of uptake and use of an internet physical activity and
      weight management program in office and manufacturing work sites in England:
      cohort study.
AB  - BACKGROUND: Internet-based physical activity (PA) and weight management programs
      have the potential to improve employees' health in large occupational health
      settings. To be successful, the program must engage a wide range of employees,
      especially those at risk of weight gain or ill health. OBJECTIVE: The aim of the
      study was to assess the use and nonuse (user attrition) of a Web-based and
      monitoring device-based PA and weight management program in a range of employees
      and to determine if engagement with the program was related to the employees'
      baseline characteristics or measured outcomes. METHODS: Longitudinal
      observational study of a cohort of employees having access to the MiLife Web
      based automated behavior change system. Employees were recruited from
      manufacturing and office sites in the North West and the South of England.
      Baseline health data were collected, and participants were given devices to
      monitor their weight and PA via data upload to the website. Website use, PA, and
      weight data were collected throughout the 12-week program. RESULTS: Overall, 12%
      of employees at the four sites (265/2302) agreed to participate in the program,
      with 130 men (49%) and 135 women (51%), and of these, 233 went on to start the
      program. During the program, the dropout rate was 5% (11/233). Of the remaining
      222 Web program users, 173 (78%) were using the program at the end of the 12
      weeks, with 69% (153/222) continuing after this period. Engagement with the
      program varied by site but was not significantly different between the office and
      factory sites. During the first 2 weeks, participants used the website, on
      average, 6 times per week, suggesting an initial learning period after which the
      frequency of website log-in was typically 2 visits per week and 7 minutes per
      visit. Employees who uploaded weight data had a significant reduction in weight (
      2.6 kg, SD 3.2, P< .001). The reduction in weight was largest for employees using
      the program's weight loss mode (-3.4 kg, SD 3.5). Mean PA level recorded
      throughout the program was 173 minutes (SE 12.8) of moderate/high intensity PA
      per week. Website interaction time was higher and attrition rates were lower (OR
      1.38, P= .03) in those individuals with the greatest weight loss. CONCLUSIONS:
      This Web-based PA and weight management program showed high levels of engagement
      across a wide range of employees, including overweight or obese workers, shift
      workers, and those who do not work with computers. Weight loss was observed at
      both office and manufacturing sites. The use of monitoring devices to capture and
      send data to the automated Web-based coaching program may have influenced the
      high levels of engagement observed in this study. When combined with objective
      monitoring devices for PA and weight, both use of the website and outcomes can be
      tracked, allowing the online coaching program to become more personalized to the
      individual.

PMID- 19117829
TI  - Antibody library-based tumor endothelial cells surface proteomic functional
      screen reveals migration-stimulating factor as an anti-angiogenic target.
AB  - Angiogenesis is critical for cancer development and metastasis. Here we have
      employed a functional antibody library-based proteomic screen to identify
      proteins that participate in and might be used as therapeutic targets for tumor
      related angiogenesis. Mice were immunized with human esophageal cancer
      endothelial cells (HECEC). The antibody library was established with the mouse
      spleen cells the serum of which had most anti-angiogenic effect. Monoclonal
      antibodies were subjected to an immunoreactive and functional screen and
      monoclonal antibodies that reacted strongly with cell surface antigens of HECECs
      and influenced their behavior were selected. Antigens that recognized by the
      antibodies were obtained by immunoprecipitation and then identified by mass
      spectrometry analysis. Migration-stimulating factor (MSF), the antigen of 1D2
      antibody was identified using this approach. Further studies demonstrated that
      the 1D2 antibody suppressed MSF-effected migration and adhesion of HECECs on
      fibronectin matrix. Biodistribution assay showed that MSF targeting antibody 1D2
      could specifically home to the xenograft with humanized blood vessel. Targeting
      treatment with 1D2 antibody significantly suppressed tumor growth through
      inhibition of human tumor-related angiogenesis. These results indicate that the
      functional antibody library-based proteomic screen can successfully identify
      proteins that involved in tumor-related angiogenesis and MSF may be a target for
      the anti-angiogenic treatment of the esophageal cancer.

PMID- 19117831
TI  - Intrauterine, early neonatal, and postdischarge growth and neurodevelopmental
      outcome at 5.4 years in extremely preterm infants after intensive neonatal
      nutritional support.
AB  - OBJECTIVE: Extremely preterm infants are at risk for poor growth and impaired
      neurodevelopment. The objective of this study was to determine whether
      intrauterine, early neonatal, or postdischarge growth is associated with
      neurocognitive and motor-developmental outcome in extremely preterm infants.
      METHODS: Surviving children who were born between July 1996 and June 1999 at <30
      weeks' gestation and with a birth weight <1500 g were evaluated at the age of
      school entry by application of (1) a standardized neurologic evaluation, (2) the
      Kaufmann Assessment Battery for Children, and (3) the Gross Motor Function
      Classification Scale. Growth was assessed on the basis of SD scores of weight and
      head circumference measured at birth, at discharge, and at the time of the follow
      up examination. All infants had received intensive early nutritional support.
      RESULTS: A total of 219 (83%) of 263 long-term survivors were evaluated at a
      median corrected age of 5.4 years. Increasing SD scores for weight and head
      circumference from birth to discharge were associated with a reduced risk for an
      abnormal neurologic examination. Catch-up growth of head circumference from birth
      to discharge was also associated with a reduced risk for impaired mobility.
      Weight SD score at birth, an increase of weight SD score from birth to discharge,
      and an increase of head circumference SD score from discharge to follow-up had an
      effect on the mental processing composite score. The effects of growth on
      neurodevelopment were by far exceeded by the consequences of intraventricular and
      periventricular hemorrhage. CONCLUSIONS: Growth from birth to discharge seemed to
      be associated with long-term motor development. Cognitive development was
      associated with intrauterine growth measured as weight at birth, early neonatal
      weight gain, and postdischarge head circumference growth. Improving particularly
      early neonatal growth may improve long-term outcome in extremely preterm infants,
      but the effects of improved growth may only be small.

PMID- 19117830
TI  - Foxp3 processing by proprotein convertases and control of regulatory T cell
      function.
AB  - Foxp3 is a 47-kDa transcription factor central to regulatory T cell (Treg)
      function. The importance of Foxp3(+) Tregs in controlling self-reactive T cells
      and preventing autoimmunity is well established. Our analysis of Foxp3 expression
      in natural Tregs led to identification of a shorter 41-kDa Foxp3 species in
      activated Tregs, indicating that Foxp3 may be processed by proteolytic cleavage
      upon cell activation. Searches of murine and human Foxp3 sequences for potential
      cleavage sites responsible for the generation of the short Foxp3 species revealed
      the presence of two RXXR proprotein convertase (PC) motifs, (48)RDLR(51) and
      (414)RKKR(417), located near the N- and C-terminal ends, respectively. We show,
      using retroviral expression of Foxp3 in CD4(+) T cells, that Foxp3 is cleaved at
      both the N- and C-terminal RXXR sites and that mutagenesis of the RXXR motif
      prevents cleavage. The cleaved forms of Foxp3 are found in the chromatin fraction
      but not in nuclear or cytoplasmic extracts. CD4(+) T cells expressing Foxp3
      species engineered to mimic N-terminally, C-terminally, or N- and C-terminally
      cleaved Foxp3 forms are functionally distinct, as indicated by differences in
      expression of key Treg genes, such as interleukin-10 and cytotoxic T-lymphocyte
      antigen 4 (CTLA-4). In addition, CD4(+) cells expressing C-cleaved Foxp3 are
      superior to those that express WT Foxp3 in preventing experimental colitis.
      Coexpression of Foxp3 with PC1 or PC7 results in cleavage of the Foxp3 C
      terminus. The mechanism by which Foxp3 is processed likely extends to other
      members of the FoxP subfamily, because Foxp1 and Foxp2 also have N-terminal RXXR
      proteolytic cleavage motifs at similar locations to Foxp3. Our results indicate
      that the generation of fully functionally competent Tregs is complex and
      dependent on the generation of multiple forms of Foxp3 that have differing
      effects on Treg cytokine production and suppressive function.

PMID- 19117832
TI  - Patient teenagers? A comparison of the sexual behavior of virginity pledgers and
      matched nonpledgers.
AB  - OBJECTIVE: The US government spends more than $200 million annually on abstinence
      promotion programs, including virginity pledges. This study compares the sexual
      activity of adolescent virginity pledgers with matched nonpledgers by using more
      robust methods than past research. SUBJECTS AND METHODS: The subjects for this
      study were National Longitudinal Study of Adolescent Health respondents, a
      nationally representative sample of middle and high school students who, when
      surveyed in 1995, had never had sex or taken a virginity pledge and who were >15
      years of age (n = 3440). Adolescents who reported taking a virginity pledge on
      the 1996 survey (n = 289) were matched with nonpledgers (n = 645) by using exact
      and nearest-neighbor matching within propensity score calipers on factors
      including prepledge religiosity and attitudes toward sex and birth control.
      Pledgers and matched nonpledgers were compared 5 years after the pledge on self
      reported sexual behaviors and positive test results for Chlamydia trachomatis,
      Neisseria gonorrhoeae, and Trichomonas vaginalis, and safe sex outside of
      marriage by use of birth control and condoms in the past year and at last sex.
      RESULTS: Five years after the pledge, 82% of pledgers denied having ever pledged.
      Pledgers and matched nonpledgers did not differ in premarital sex, sexually
      transmitted diseases, and anal and oral sex variables. Pledgers had 0.1 fewer
      past-year partners but did not differ in lifetime sexual partners and age of
      first sex. Fewer pledgers than matched nonpledgers used birth control and condoms
      in the past year and birth control at last sex. CONCLUSIONS: The sexual behavior
      of virginity pledgers does not differ from that of closely matched nonpledgers,
      and pledgers are less likely to protect themselves from pregnancy and disease
      before marriage. Virginity pledges may not affect sexual behavior but may
      decrease the likelihood of taking precautions during sex. Clinicians should
      provide birth control information to all adolescents, especially virginity
      pledgers.

PMID- 19117833
TI  - Effect of bimonthly supplementation with oral cholecalciferol on serum 25
      hydroxyvitamin D concentrations in HIV-infected children and adolescents.
AB  - OBJECTIVE: Vitamin D insufficiency occurs commonly in HIV-infected youth in the
      United States. In light of the importance of vitamin D for skeletal and
      nonskeletal health, including innate immunity, developing methods for improving
      vitamin D status in HIV-infected children and adolescents is an important area of
      clinical research. The objective of this study was to evaluate the effect of
      administration of oral cholecalciferol, 100,000 IU every 2 months, and 1 g/day
      calcium on serum 25-hydroxyvitamin D concentrations, serum and urine calcium, and
      HIV disease progression during a 12-month period. METHODS: HIV-infected children
      and adolescents who were aged 6 to 16 years were randomly assigned to receive
      vitamin D (100,000 IU bimonthly) and calcium (1 g/day; n = 29) or double placebo
      (n = 27). Serum 25-hydroxyvitamin D concentrations as measured by
      radioimmunoassay, albumin-corrected calcium concentrations, and spot urinary
      calcium-creatinine ratios were determined monthly. RESULTS: No abnormalities in
      serum calcium concentration were observed. One participant who received placebo
      developed hypercalciuria. No group differences were seen in the change in CD4
      count or CD4% or viral load during 12 months. The overall mean monthly serum 25
      hydroxyvitamin D concentrations were higher in the group that received vitamin D
      and calcium than in the placebo group, as was the monthly serum 25-hydroxyvitamin
      D area under the curve. After completing 12 months of study, 2 (6.7%)
      participants in the group that received vitamin D and calcium had a trough serum
      25-hydroxyvitamin D concentration <20 ng/mL compared with 14 (50%) in the placebo
      group. Twelve (44.4%) in the group that received vitamin D and calcium had a
      trough serum 25-hydroxyvitamin D concentration of > or =30 ng/mL compared with 3
      (11.1%) in the placebo group. CONCLUSIONS: Administration of oral cholecalciferol
      to HIV-infected children and adolescents at a dosage of 100,000 IU every 2
      months, together with 1 g/day calcium, is safe and results in significant
      increases in serum 25-hydroxyvitamin D concentrations.

PMID- 19117834
TI  - Pedometer accuracy for children: can we recommend them for our obese population?
AB  - OBJECTIVE: In this study, we investigated the accuracy of measuring walking steps
      with commercially available pedometers and an accelerometer-based step-counter in
      normal and overweight children. Our primary hypothesis was that commercially
      available pedometers are not an accurate measure of walking steps in normal and
      overweight children while walking. Our secondary hypothesis was that the
      accelerometer-based step-counter provides an accurate measure of walking steps in
      normal and overweight children. METHODS: Thirteen boys (11 +/- 1 years) and 14
      girls (11 +/- 1 years) who ranged in BMI from 15 to 27 kg/m(2) (16 normal and 11
      overweight or obese) were recruited. Each child wore 4 pedometers at the waist
      and 1 accelerometer-based step-counter on each ankle. Steps were manually counted
      and energy expenditure was measured while the child walked on the treadmill at
      0.5, 1.0, 1.5, and 2.0 mph, each for 5 minutes. The step-counting devices were
      also validated while children walked on level ground at a self-selected pace.
      RESULTS: For the commercially available pedometers at the lowest speed of 0.5
      mph, the percentage error approximated 100% for both of the pedometers. At the
      fastest speed of 2.0 mph, the percentage error approximated 60%. Conversely the
      accelerometer-based step-counter showed a percentage error of 24% +/- 22% (mean
      +/- SD) at 0.5 mph; however, as walking speed increased, the error declined to 5%
      +/- 8% at 1.0 mph, 4% +/- 5% at 1.5 mph, and 2% +/- 2% at 2.0 mph. The
      relationship between steps counted and walking energy expenditure showed good
      linear correlation. CONCLUSIONS: Commercially available pedometers are less
      accurate for measuring walking and require discretion in their use for children.
      The accuracy of the accelerometer-based step-counter enables it to be used as a
      tool to assess and potentially promote physical activity in normal and overweight
      children.

PMID- 19117835
TI  - Failure of ductus arteriosus closure is associated with increased mortality in
      preterm infants.
AB  - OBJECTIVE: Because the standard of care has been to attempt to close the patent
      ductus arteriosus in preterm neonates, there is a paucity of information on the
      outcome of patients with a persistent patent ductus arteriosus. Our objective was
      to compare the mortality of preterm infants with and without a persistent patent
      ductus arteriosus. METHODS: This was a single-center, retrospective study. Very
      preterm infants (birth weight < or = 1500 g and gestational age < or = 29 weeks)
      who survived beyond the first 3 postnatal days and did not undergo surgical
      ligation were included in the primary analysis. Mortality of neonates with a
      persistent and a closed patent ductus arteriosus was compared during the initial
      hospitalization by using the chi(2) test. Cox proportional hazard regression and
      logistic regression were used to take into account the time until death and
      assess the independent effect of each risk factor on mortality. We also performed
      3 secondary analyses by excluding patients who died during the first 7 and 14
      postnatal days and including patients who underwent surgical ligation by using
      different group assignments. A persistent patent ductus arteriosus was defined as
      a failure of either spontaneous or pharmacologic ductal closure during the
      initial hospitalization. RESULTS: Patients with a persistent patent ductus
      arteriosus (n = 41) had lower birth weight and were less mature than those with a
      closed ductus (n = 260). Unadjusted mortality rate was higher in patients with a
      persistent (70.7%) than with a closed (11.2%) ductus. After adjustment for
      perinatal factors, level of maturity, disease severity, and morbid pathologies,
      the hazard for death in neonates with a persistent ductus was eightfold higher
      than in those with a closed ductus. Exclusion of patients who died during the
      first 2 weeks or inclusion of those who underwent ductal ligation did not change
      the findings. CONCLUSION: Failure of ductal closure is associated with an
      increase in mortality in very preterm infants.

PMID- 19117836
TI  - Planning for health care transitions: results from the 2005-2006 National Survey
      of Children With Special Health Care Needs.
AB  - OBJECTIVES: Many youth with special health care needs have difficulties
      transferring to adult medical care. To address this, the Maternal and Child
      Health Bureau has made receipt of transition services a core performance outcome
      for community-based systems of care for youth with special health care needs. In
      this article we describe the results for the transition core outcome from the
      2005-2006 National Survey of Children With Special Health Care Needs. We also
      describe changes in the measurement strategy for this outcome since the first
      National Survey of Children With Special Health Care Needs in 2001. METHODS: In
      the nationally representative, cross-sectional 2005-2006 National Survey of
      Children With Special Health Care Needs, parent or guardian respondents of 18198
      youth with special health care needs (aged 12-17) were asked if they have had
      discussions with their child's health care providers about (1) future adult
      providers, (2) future adult health care needs, (3) changes in health insurance,
      and (4) encouraging their child to take responsibility for his or her care. All 4
      components had to be met for the youth to meet the overall transition core
      outcome. Those who had not had transition discussions reported if such
      discussions would have been helpful. RESULTS: Overall, 41% of youth with special
      health care needs met the core performance outcome for transition. Forty-two
      percent had discussed shifting care to an adult provider, 62% discussed their
      child's adult health care needs, and 34% discussed upcoming changes in health
      insurance. Most (78%) respondents said that providers usually or always encourage
      their child to take responsibility for his or her health. Non-Hispanic black or
      Hispanic race/ethnicity, lower income level, not speaking English, and not having
      a medical home reduced the odds of meeting the transition core outcome.
      CONCLUSIONS: Current performance on the transition core outcome leaves much room
      for improvement. Many parents feel that having transition-related discussions
      with their health care providers would be helpful. Future clinical and policy
      level research should be directed at identifying barriers to, and recommending
      content for, health transition discussions.

PMID- 19117837
TI  - Trends in the diagnosis of overweight and obesity in children and adolescents:
      1999-2007.
AB  - OBJECTIVE: Pediatric overweight and obesity are increasingly prevalent problems
      and have received much attention in recent years, but it is unclear whether this
      publicity has affected diagnosis by clinicians. We undertook the current study to
      assess trends in diagnosis rates of overweight and obesity in children. PATIENTS
      AND METHODS: We analyzed electronic medical record data from 60711 patients aged
      2 through 18 years with at least 1 well-child visit between June 1999 and October
      2007 in a large academic medical system in northeast Ohio. Diagnosis of weight
      problems among children classified as overweight and obese was assessed by using
      International Classification of Diseases, Ninth Revision codes. Logistic
      regression was used to examine the impact of patient characteristics on diagnosis
      and to investigate trends over the study period. RESULTS: On retrospective review
      of BMI measurements recorded for patients during the study period, 19% of the
      children were overweight, 23% were obese, and 8% (33% of the obese patients) were
      severely obese; among these, 10% of overweight patients, 54% of obese patients,
      and 76% of severely obese patients had their conditions diagnosed. BMI, age, and
      number of overweight visits were positively associated with diagnosis. Female
      patients were more likely to have been diagnosed than male patients. Black and
      Hispanic patients were more likely to have been diagnosed than white patients.
      There was a statistically significant trend toward increasing diagnosis during
      the study period, although the percentage of patients diagnosed per year seemed
      to plateau or decrease after 2005. CONCLUSIONS: Although clear BMI definitions of
      pediatric weight problems exist, a large percentage of overweight and obese
      patients remain undiagnosed. Diagnosis increased during the study period but
      remained low among overweight children, for whom early intervention may be more
      effective. Identification of overweight and obese patients is the first step in
      addressing this growing epidemic.

PMID- 19117838
TI  - The problem with Dr Bob's alternative vaccine schedule.
AB  - In October 2007, Dr Robert Sears, in response to growing parental concerns about
      the safety of vaccines, published The Vaccine Book: Making the Right Decision for
      Your Child. Sears' book is enormously popular, having sold >40000 copies. At the
      back of the book, Sears includes "Dr Bob's Alternative Vaccine Schedule," a
      formula by which parents can delay, withhold, separate, or space out vaccines.
      Pediatricians now confront many parents who insist that their children receive
      vaccines according to Sears' schedule, rather than that recommended by the
      American Academy of Pediatrics, the Centers for Disease Control and Prevention,
      and the American Academy of Family Physicians. This article examines the reasons
      for the popularity of Sears' book, deconstructs the logic and rationale behind
      its recommendations, and describes how Sears' misrepresentation of vaccine
      science misinforms parents trying to make the right decisions for their children.

PMID- 19117839
TI  - Apparent life-threatening events and over-the-counter cough and cold medications.

PMID- 19117840
TI  - Pediatric autoimmune neuropsychiatric disorders associated with streptococcus.

PMID- 19117841
TI  - Early antibiotic treatment of pyelonephritis in children is still mandatory.

PMID- 19117842
TI  - Early antibiotic treatment of pyelonephritis in children is still mandatory.

PMID- 19117843
TI  - New Advisory Committee on Immunization Practices guidelines for rotavirus vaccine
      allow more children to receive vaccine.

PMID- 19117844
TI  - Response to the commentary "Advancing medical education training in adolescent
      health".

PMID- 19117845
TI  - Juggling work and breastfeeding: effects of maternity leave and occupational
      characteristics.
AB  - OBJECTIVES: Juggling breastfeeding and paid work can challenge breastfeeding
      success. We examined the relationship between breastfeeding and maternity leave
      before and after delivery among working mothers in Southern California.
      California is 1 of only 5 states in the United States providing paid pregnancy
      leave that can be extended for infant bonding. PATIENTS AND METHODS: Drawing from
      a case-control study of preterm birth and low birth weight, 770 full-time working
      mothers were compared on whether they established breastfeeding in the first
      month. For those who established breastfeeding, we examined duration. Eligible
      women participated in California's Prenatal Screening Program; delivered live
      births between July 2002 and December 2003; were > or =18 years old; had a
      singleton birth without congenital anomalies; and had a US mailing address. We
      assessed whether maternity leave and other occupational characteristics predicted
      breastfeeding cessation and used multivariate regression models weighted for
      probability of sampling to calculate odds ratios for breastfeeding establishment
      and hazards ratios for breastfeeding cessation. RESULTS: A maternity leave of <
      or =6 weeks or 6 to 12 weeks after delivery was associated, respectively, with a
      fourfold and twofold higher odds of failure to establish breastfeeding and an
      increased probability of cessation after successful establishment, relative to
      women not returning to work, after adjusting for covariates. The impact of short
      postpartum leave on breastfeeding cessation was stronger among nonmanagers, women
      with inflexible jobs, and with high psychosocial distress. Antenatal leave in the
      last month of pregnancy was not associated with breastfeeding establishment or
      duration. CONCLUSIONS: Postpartum maternity leave may have a positive effect on
      breastfeeding among full-time workers, particularly those who hold nonmanagerial
      positions, lack job flexibility, or experience psychosocial distress.
      Pediatricians should encourage patients to take maternity leave and advocate for
      extending paid postpartum leave and flexibility in working conditions for
      breastfeeding women.

PMID- 19117846
TI  - Psychiatric morbidity in adolescents and young adults born preterm: a Swedish
      national cohort study.
AB  - OBJECTIVE: Increasing numbers of infants born preterm survive into adulthood.
      Previous studies have reported increased levels of neurologic and cognitive
      disabilities in these children. In this study, we analyzed the effect of having
      been born preterm on psychiatric morbidity. METHODS: A Swedish national cohort of
      545628 individuals born in 1973-1979 was followed up in the national registers
      during 1987-2002. Multivariate Cox analysis of proportional hazards was used to
      estimate the hazard ratios of hospital admissions for psychiatric disorders and
      alcohol/illicit drug abuse. RESULTS: There was a stepwise increase in psychiatric
      hospital admissions with an increasing degree of preterm birth. A total of 5.2%
      of children born at 24 to 28 weeks' gestation and 3.5% born at 29 to 32 weeks'
      gestation had been hospitalized because of a psychiatric disorder. The hazard
      ratios for psychiatric disorders were 1.68 in the group of very preterm children
      (gestational weeks 24-32), 1.21 in the moderately preterm group (gestational
      weeks 33-36), and 1.08 in the early term group (gestational weeks 37-38) after
      adjustment for socioeconomic confounders. Moderately preterm and early term birth
      accounted for 85% of the risk attributed to preterm/early term birth. The effect
      of preterm birth was greater in households with low socioeconomic status.
      CONCLUSION: Preterm birth carries some risk for psychiatric disorders requiring
      hospitalization in adolescence and young adulthood (ages 8-29 years). Even if
      this risk increases with degree of preterm birth, most subjects are moderately
      preterm, a group in need of more attention in research and secondary prevention.

PMID- 19117847
TI  - Assessing the impact of the introduction of the World Health Organization growth
      standards and weight-for-height z-score criterion on the response to treatment of
      severe acute malnutrition in children: secondary data analysis.
AB  - OBJECTIVE: The objective of our study was to assess the impact of adopting the
      World Health Organization growth standards and weight-for-height z-score
      criterion on the response to treatment of severe acute malnutrition in children
      compared with the use of the National Center for Health Statistics growth
      reference. METHODS: We used data from children aged 6 to 59 months with acute
      malnutrition who were admitted to the Medecins sans Frontieres nutrition program
      in Maradi, Niger, during 2006 (N = 56214). Differences in weight gain, duration
      of treatment, recovery from malnutrition, mortality, loss to follow-up, and need
      for inpatient care were compared for severely malnourished children identified
      according to the National Center for Health Statistics reference and weight-for
      height <70% of the median criterion versus the World Health Organization
      standards and the weight-for-height less than -3 z-score criterion. RESULTS: A
      total of 8 times more children (n = 25754) were classified as severely
      malnourished according to the World Health Organization standards compared with
      the National Center for Health Statistics reference (n = 2989). Children included
      according to the World Health Organization standards had shorter durations of
      treatment, greater rates of recovery, fewer deaths, and less loss to follow-up or
      need for inpatient care. CONCLUSIONS: The introduction of the World Health
      Organization standards with the z-score criterion to identify children for
      admission into severe acute malnutrition treatment programs would imply the
      inclusion of children who are younger but have relatively higher weight for
      height on admission compared with the National Center for Health Statistics
      reference. These children have fewer medical complications requiring inpatient
      care and are more likely to experience shorter durations of treatment and lower
      mortality rates. The World Health Organization standards with the z-score
      criterion might become a useful tool for the early detection of acute
      malnutrition in children, although additional research on the resource
      implications of this transition is required.

PMID- 19117848
TI  - School absenteeism, health status, and health care utilization among children
      with asthma: associations with parental chronic disease.
AB  - OBJECTIVE: Parents with chronic disease may be more likely than healthy parents
      to perceive their children with chronic conditions as medically vulnerable. Our
      objective for this study was to determine if children with asthma whose parents
      have chronic disease differ in health care utilization, school absenteeism, and
      reported child health status compared with those whose parents do not have
      chronic disease. PATIENTS AND METHODS: We selected children with asthma, 5 to 17
      years of age, and their parents from the 2003 National Health Interview Survey.
      We determined whether parents had chronic disease and examined associations of
      parental chronic disease with child health status, school absenteeism, and health
      care utilization. We controlled for factors known to influence our dependent
      variables, including an indicator of child disease severity, in multivariable
      regression. RESULTS: Among 561 parent-child dyads, children with asthma whose
      parents had chronic disease were more likely to have less than very good health
      and missed an average of 1.3 more school days annually than other children with
      asthma. Among children with less severe asthma, those whose parents had chronic
      disease had lower reported health status but did not miss more school (mean
      difference: 0.39) than children whose parents did not have chronic disease.
      Having a parent with chronic disease was not associated with increased health
      care utilization. CONCLUSIONS: Compared with other children with asthma, children
      whose parents have chronic disease have worse health status and miss more school,
      particularly among children with more severe asthma. Understanding how parents'
      health influences children's health care and health status may help providers
      work with parents to more effectively and efficiently manage their children's
      asthma care so they can more fully participate in school and other activities.

PMID- 19117849
TI  - Contribution of early weight gain to childhood overweight and metabolic health: a
      longitudinal study (EarlyBird 36).
AB  - BACKGROUND: Early weight gain (0-5 years) is thought to be an important
      contributor to childhood obesity and consequently metabolic risk. There is a
      scarcity of longitudinal studies in contemporary children reporting the impact of
      early weight gain on metabolic health. OBJECTIVE: We aimed to assess the impact
      of early weight gain on metabolic health at 9 years of age. METHOD: Two hundred
      thirty-three children (134 boys, 99 girls) with a gestational age of >37 weeks
      were assessed at birth, 5 years of age, and 9 years of age. Measures included
      weight SD scores at each time point and excess weight gained (Delta weight SD
      score) between them. The outcome measure included composite metabolic score (sum
      of internally derived z scores of insulin resistance, mean blood pressure,
      triglyceride level, and total cholesterol/high-density lipoprotein cholesterol
      ratio). RESULTS: Weight SD score increased by 0.29 SD score in girls and 0.26 SD
      score in boys from 0 to 5 years of age and by 0.03 SD score in girls and 0.11 SD
      score in boys from 5 to 9 years of age. Weight SD score correlated poorly to
      moderately before 5 years of age but strongly after 5 years of age. Birth weight
      SD score predicted (girls/boys) 2.4%/0% of the variability in composite metabolic
      score at 9 years of age. Adding Delta weight SD score (0-5 years old) contributed
      (girls/boys) 11.2%/7.0% to the score, and adding Delta weight SD score (5-9 years
      old) additionally contributed (girls/boys) 26.4%/16.5%. Importantly, once weight
      SD score at 9 years of age was known, predictive strength was changed little by
      adding Delta weight SD score. CONCLUSIONS: Most excess weight before puberty is
      gained before 5 years of age. Weight at 5 years of age bears little relation to
      birth weight but closely predicts weight at 9 years of age. Single measures of
      current weight are predictive of metabolic health, whereas weight gain within a
      specific period adds little. A single measure of weight at 5 years of age
      provides a pointer to future health for the individual. If metabolic status at 9
      years of age means future risk, diabetes/cardiovascular prevention strategies
      might better focus on preschool-aged children, because the die seems to be
      largely cast by 5 years of age, and a healthy weight early in childhood may be
      maintained at least into puberty.

PMID- 19117850
TI  - Beliefs about the health effects of "thirdhand" smoke and home smoking bans.
AB  - OBJECTIVE: There is no safe level of exposure to tobacco smoke. Thirdhand smoke
      is residual tobacco smoke contamination that remains after the cigarette is
      extinguished. Children are uniquely susceptible to thirdhand smoke exposure. The
      objective of this study was to assess health beliefs of adults regarding
      thirdhand smoke exposure of children and whether smokers and nonsmokers differ in
      those beliefs. We hypothesized that beliefs about thirdhand smoke would be
      associated with household smoking bans. METHODS: Data were collected by a
      national random-digit-dial telephone survey from September to November 2005. The
      sample was weighted by race and gender within Census region on the basis of US
      Census data. The study questions assessed the level of agreement with statements
      that breathing air in a room today where people smoked yesterday can harm the
      health of children. RESULTS: Of 2000 eligible respondents contacted, 1510 (87%)
      completed surveys, 1478 (97.9%) answered all questions pertinent to this
      analysis, and 273 (18.9%) were smokers. Overall, 95.4% of nonsmokers versus 84.1%
      of smokers agreed that secondhand smoke harms the health of children, and 65.2%
      of nonsmokers versus 43.3% of smokers agreed that thirdhand smoke harms children.
      Strict rules prohibiting smoking in the home were more prevalent among
      nonsmokers: 88.4% vs 26.7%. In multivariate logistic regression, after
      controlling for certain variables, belief that thirdhand smoke harms the health
      of children remained independently associated with rules prohibiting smoking in
      the home. Belief that secondhand smoke harms the health of children was not
      independently associated with rules prohibiting smoking in the home and car.
      CONCLUSIONS: This study demonstrates that beliefs about the health effects of
      thirdhand smoke are independently associated with home smoking bans. Emphasizing
      that thirdhand smoke harms the health of children may be an important element in
      encouraging home smoking bans.

PMID- 19117851
TI  - Physical fitness and physical activity at age 13 years as predictors of
      cardiovascular disease risk factors at ages 15, 25, 33, and 40 years: extended
      follow-up of the Oslo Youth Study.
AB  - OBJECTIVE: Few studies have examined the association of childhood physical
      activity and physical fitness with cardiovascular disease risk factors in
      adulthood. Furthermore, interpretation of these findings is hampered by
      methodologic shortcomings. In a population-based cohort study, we explored the
      influence, if any, of childhood physical activity and physical fitness on later
      cardiovascular disease risk factors. METHODS: Data were taken from the Oslo Youth
      Study, a prospective cohort study that began in 1979, when 1016 students (mean
      age: 13 years; range: 11-15 years) who were attending 6 schools were invited to
      participate in a health education intervention. Cardiovascular disease risk
      factor data were collected at baseline and again in 1981 (mean age: 15 years;
      range: 13-17 years), 1991 (mean age: 25; range: 23-27 years), 1999 (mean age: 33;
      range: 31-35 years), and 2006 (mean age: 40; range: 38-42 years). RESULTS: At
      baseline, physical fitness was inversely related to BMI, triceps skinfold
      thickness, and blood pressure (systolic and diastolic; N = 716). These
      associations were also present in prospective analyses at ages 15 (N = 472), 25
      (N = 280; except for systolic blood pressure), and 33 years (N = 410, only BMI
      measured)-albeit with progressively diminishing magnitude-but were lost at 40
      years (N = 294). There were fewer relationships with cardiovascular disease risk
      factors when physical activity was the exposure of interest. Controlling for
      educational attainment of both the parent and the study member had little impact
      on these associations. CONCLUSIONS: Although childhood physical fitness seems to
      reveal some inverse associations with obesity and blood pressure in early
      adulthood, these effects diminished markedly into middle age.

PMID- 19117852
TI  - Construction of a parent-derived questionnaire to measure end-of-life care after
      withdrawal of life-sustaining treatment in the neonatal intensive care unit.
AB  - OBJECTIVES: The objective of this study was to develop and pretest a
      questionnaire to assess the practice of withdrawal of life-sustaining treatment
      in the NICU on the basis of the experiences of bereaved parents. METHODS: We
      conducted semistructured interviews with 11 parents whose infants had undergone
      withdrawal of life-sustaining treatment in the NICU at McMaster University
      Medical Centre to obtain their views on helpful practices. Interviews continued
      until no new items were obtained (ie, saturation point). A total of 370 items
      were distilled into 82 questionnaire statements on care by a multidisciplinary
      team and grouped for analysis into 6 domains: communication, quality of care,
      quality of life, shared decision-making, withdrawal of life-sustaining treatment
      process, and bereavement care. Respondents were asked to rank how frequently
      events occurred on a 7-point Likert scale anchored from 1 = never to 7 = always.
      A score of >5 was considered favorable. The questionnaire was distributed to a
      pretest sample of perinatal social workers who attended a bereavement workshop at
      an international conference. RESULTS: The response rate was 48%. Respondents
      ranked items that pertained to the withdrawal of life-sustaining treatment
      process highest, indicating that items were done well. Items related to quality
      of care and bereavement care ranked lowest. Other domains ranked as follows:
      communication, shared decision-making, and quality of life. Consistency of items
      within domains was tested by Cronbach's alpha and split-half testing and were
      >0.6 for most domains. CONCLUSIONS: Parents' views on important aspects of end-of
      life care in the NICU were incorporated into a quality assurance questionnaire.
      Pretesting assessed the performance of the instrument and the perceptions of
      social workers on the effectiveness of end-of-life practices. Respondents
      identified that parents' practical needs were met during the withdrawal process
      but were not consistently met in regard to the quality of in-hospital and follow
      up bereavement care.

PMID- 19117853
TI  - Prevalence and time course of acute mountain sickness in older children and
      adolescents after rapid ascent to 3450 meters.
AB  - OBJECTIVE: Acute mountain sickness is a frequent and debilitating complication of
      high-altitude exposure, but there is little information on the prevalence and
      time course of acute mountain sickness in children and adolescents after rapid
      ascent by mechanical transportation to 3500 m, an altitude at which major tourist
      destinations are located throughout the world. METHODS: We performed serial
      assessments of acute mountain sickness (Lake Louise scores) in 48 healthy
      nonacclimatized children and adolescents (mean +/- SD age: 13.7 +/- 0.3 years; 20
      girls and 28 boys), with no previous high-altitude experience, 6, 18, and 42
      hours after arrival at the Jungfraujoch high-altitude research station (3450 m),
      which was reached through a 2.5-hour train ascent. RESULTS: We found that the
      overall prevalence of acute mountain sickness during the first 3 days at high
      altitude was 37.5%. Rates were similar for the 2 genders and decreased
      progressively during the stay (25% at 6 hours, 21% at 18 hours, and 8% at 42
      hours). None of the subjects needed to be evacuated to lower altitude. Five
      subjects needed symptomatic treatment and responded well. CONCLUSION: After rapid
      ascent to high altitude, the prevalence of acute mountain sickness in children
      and adolescents was relatively low; the clinical manifestations were benign and
      resolved rapidly. These findings suggest that, for the majority of healthy
      nonacclimatized children and adolescents, travel to 3500 m is safe and
      pharmacologic prophylaxis for acute mountain sickness is not needed.

PMID- 19117854
TI  - Utility of lumbar puncture for first simple febrile seizure among children 6 to
      18 months of age.
AB  - OBJECTIVES: American Academy of Pediatrics consensus statement recommendations
      are to consider strongly for infants 6 to 12 months of age with a first simple
      febrile seizure and to consider for children 12 to 18 months of age with a first
      simple febrile seizure lumbar puncture for cerebrospinal fluid analysis. Our aims
      were to determine compliance with these recommendations and to assess the rate of
      bacterial meningitis detected among these children. METHODS: A retrospective
      cohort review was performed for patients 6 to 18 months of age who were evaluated
      for first simple febrile seizure in a pediatric emergency department between
      October 1995 and October 2006. RESULTS: First simple febrile seizure accounted
      for 1% of all emergency department visits for children of this age, with 704
      cases among 71 234 eligible visits during the study period. Twenty-seven percent
      (n = 188) of first simple febrile seizure visits were for infants 6 to 12 months
      of age, and 73% (n = 516) were for infants 12 to 18 months of age. Lumbar
      puncture was performed for 38% of the children (n = 271). Samples were available
      for 70% of children 6 to 12 months of age (131 of 188 children) and 25% of
      children 12 to 18 months of age (129 of 516 children). Rates of lumbar puncture
      decreased significantly over time in both age groups. The cerebrospinal fluid
      white blood cell count was elevated in 10 cases (3.8%). No pathogen was
      identified in cerebrospinal fluid cultures. Ten cultures (3.8%) yielded a
      contaminant. No patient was diagnosed as having bacterial meningitis.
      CONCLUSIONS: The risk of bacterial meningitis presenting as first simple febrile
      seizure at ages 6 to 18 months is very low. Current American Academy of
      Pediatrics recommendations should be reconsidered.

PMID- 19117855
TI  - Obesity and excessive daytime sleepiness in prepubertal children with obstructive
      sleep apnea.
AB  - INTRODUCTION: The epidemic of childhood obesity has prompted remarkable changes
      in the relative proportions of symptomatic overweight or obese children being
      referred for evaluation of habitual snoring. However, it remains unclear whether
      obesity modifies the relative frequency of daytime symptoms such as excessive
      daytime sleepiness. METHODS: Fifty consecutive, nonobese, habitually snoring,
      otherwise-healthy children (age range: 6-9 years) and 50 age-, gender-, and
      ethnicity-matched obese children (BMI z score: >1.67) underwent an overnight
      polysomnographic evaluation, followed by a multiple sleep latency test the
      following day. RESULTS: The mean obstructive apnea/hypopnea index values for the
      2 groups were similar (nonobese: 12.0 +/- 1.7 episodes per hour of total sleep
      time; obese: 10.9 +/- 1.5 episodes per hour of total sleep time). However, the
      mean sleep latency for obese children was significantly shorter (12.9 +/- 0.9
      minutes) than that for nonobese children (17.9 +/- 0.7 minutes). Furthermore, 21
      obese children had mean sleep latencies of < or =12.0 minutes, compared with only
      5 nonobese children. Although significant associations emerged between mean sleep
      latency, obstructive apnea/hypopnea index, proportion of total sleep time with
      oxygen saturation of <95%, and respiratory arousal index for the whole cohort,
      the slopes and intersects of the linear correlation of mean sleep latency with
      any of these polygraphic measures were consistently greater in the obese cohort.
      CONCLUSIONS: The likelihood of excessive daytime sleepiness for obese children is
      greater than that for nonobese children at any given level of obstructive sleep
      apnea severity and is strikingly reminiscent of excessive daytime sleepiness
      patterns in adults with obstructive sleep apnea.

PMID- 19117856
TI  - Mucopolysaccharidosis I: management and treatment guidelines.
AB  - OBJECTIVE: Disease management for mucopolysaccharidosis type I has been
      inconsistent because of disease rarity (approximately 1 case per 100,000 live
      births), phenotypic heterogeneity, and limited therapeutic options. The
      availability of hematopoietic stem cell transplantation and the recent
      introduction of enzyme replacement therapy for mucopolysaccharidosis I
      necessitate the establishment of system-specific management guidelines for this
      condition. METHODS: Twelve international experts on mucopolysaccharidosis I met
      in January 2003 to draft management and treatment guidelines for
      mucopolysaccharidosis I. Initial guidelines were revised and updated in 2008, on
      the basis of additional clinical data and therapeutic advances. Recommendations
      are based on our extensive clinical experience and a review of the literature.
      RESULTS: All patients with mucopolysaccharidosis I should receive a comprehensive
      baseline evaluation, including neurologic, ophthalmologic, auditory, cardiac,
      respiratory, gastrointestinal, and musculoskeletal assessments, and should be
      monitored every 6 to 12 months with individualized specialty assessments, to
      monitor disease progression and effects of intervention. Patients are best
      treated by a multidisciplinary team. Treatments consist of palliative/supportive
      care, hematopoietic stem cell transplantation, and enzyme replacement therapy.
      The patient's age (>2 years or < or =2 years), predicted phenotype, and
      developmental quotient help define the risk/benefit profile for hematopoietic
      stem cell transplantation (higher risk but can preserve central nervous system
      function) versus enzyme replacement therapy (low risk but cannot cross the blood
      brain barrier). CONCLUSION: We anticipate that provision of a standard of care
      for the treatment of patients with mucopolysaccharidosis I will optimize clinical
      outcomes and patients' quality of life.

PMID- 19117857
TI  - Latent tuberculosis diagnosis in children by using the QuantiFERON-TB Gold In
      Tube test.
AB  - BACKGROUND: The QuantiFERON-TB Gold test was the first blood test to be approved
      for the diagnosis of latent tuberculosis infection. Although it has been shown to
      be sensitive and specific in adults, limited data on its performance in children
      are available. METHODS: This was a prospective study of children receiving health
      care in New York, New York. Each child was assessed for risk factors for
      Mycobacterium tuberculosis infection, underwent tuberculin skin testing, and had
      a QuantiFERON-TB Gold In-Tube test performed. The concordance between tuberculin
      skin test and QuantiFERON-TB Gold In-Tube test results was calculated, and the
      results were analyzed according to the likelihood of exposure to M tuberculosis.
      RESULTS: Data for 207 children with valid tuberculin skin test and QuantiFERON-TB
      Gold In-Tube test results were analyzed. There was excellent correlation between
      negative tuberculin skin test results and negative QuantiFERON-TB Gold In-Tube
      test results; however, only 23% of children with positive tuberculin skin test
      results had positive QuantiFERON-TB Gold In-Tube test results. Positive
      QuantiFERON-TB Gold In-Tube test results were associated with increased
      likelihood of M tuberculosis exposure, and interferon gamma levels were higher in
      children with known recent exposure to M tuberculosis, compared with children
      with older exposure histories. Younger children produced lower interferon gamma
      levels in response to the mitogen (phytohemagglutinin) control used in the
      QuantiFERON-TB Gold In-Tube test, but indeterminant results were low for children
      of all ages. Performance characteristics were similar across all age groups.
      CONCLUSION: The QuantiFERON-TB Gold In-Tube test is a specific test for M
      tuberculosis exposure in children, with performance characteristics similar to
      those for adults residing in regions with low levels of endemic disease. Concerns
      about test sensitivity, especially for children <2 years of age, will require
      additional prospective long-term evaluation.

PMID- 19117858
TI  - Comparison of T-SPOT.TB assay and tuberculin skin test for the evaluation of
      young children at high risk for tuberculosis in a community setting.
AB  - OBJECTIVE: We wished to compare the sensitivity of an enzyme-linked immunospot
      assay (T-SPOT.TB; Oxford Immunotec, Oxford, United Kingdom) and the tuberculin
      skin test for the detection of tuberculosis infection in very young children
      being evaluated for active tuberculosis in a rural community setting. METHODS:
      Children with a history of exposure to tuberculosis and children presenting to a
      local clinic or hospital with symptoms suggesting tuberculosis were admitted to a
      dedicated case verification ward. T-SPOT.TB testing was performed, and children
      were evaluated with a clinical examination, a tuberculin skin test, chest
      radiographs, and cultures of induced sputum and gastric lavage specimens. The
      diagnosis was determined by using a clinical algorithm. RESULTS: A total of 243
      children (median age: 18 months) were recruited, of whom 214 (88%) had
      interpretable T-SPOT.TB results. Children > or =12 months of age were more likely
      than younger children to have positive T-SPOT.TB results, whereas tuberculin skin
      test results were unaffected by age. The sensitivity of the T-SPOT.TB was no
      better than that of the tuberculin skin test for culture-confirmed tuberculosis
      (50% and 80%, respectively) and was poorer for the combined group of culture
      confirmed and clinically probable tuberculosis (40% and 52%, respectively). For
      the 50 children clinically categorized as not having tuberculosis, the
      specificity of both the T-SPOT.TB and the tuberculin skin test was 84%.
      CONCLUSIONS: For young children presenting in a community setting after exposure
      to tuberculosis or with symptoms suggesting tuberculosis, T-SPOT.TB cannot be
      used to exclude active disease. The sensitivity of this assay may be impaired for
      very young children.

PMID- 19117859
TI  - Reduction in the incidence of chronic lung disease in very low birth weight
      infants: results of a quality improvement process in a tertiary level neonatal
      intensive care unit.
AB  - OBJECTIVE: Our objective was to reduce the incidence of chronic lung disease by
      introducing potentially better practices in our delivery room and NICU. METHODS:
      We compared the incidences of chronic lung disease in infants with birth weights
      of 501 to 1500 g in 2002 and 2005, after implementation of the changes. Medical
      records for infants of 501 to 1500 g who were born in 2002 and 2005 were reviewed
      for maternal characteristics, care of the infant in the delivery room and the
      NICU (including surfactant usage, duration of ventilation, duration of continuous
      positive airway pressure therapy, and duration of oxygen treatment), length of
      stay, and short-term clinical outcomes (eg, pneumothorax, severe intracranial
      hemorrhage, retinopathy of prematurity, and weight gain). RESULTS: There was a
      significant reduction in our incidence of chronic lung disease, from 46.5% in
      2002 to 20.5% in 2005. The number of infants discharged from the hospital with
      oxygen therapy also decreased significantly, from 16.4% in 2002 to 4.1% in 2005.
      The overall relative risk reduction for chronic lung disease in 2005, compared
      with 2002, was 55.8%. CONCLUSIONS: By using a quality improvement process that
      included avoidance of intubation, adoption of new pulse oximeter limits, and
      early use of nasal continuous positive airway pressure therapy, we demonstrated a
      significant reduction in the incidence of chronic lung disease in infants with
      birth weights of <1500 g in 2005, in comparison with 2002. These results have
      persisted to date. There were no significant short-term complications.

PMID- 19117860
TI  - Nutritional practices in the neonatal intensive care unit: analysis of a 2006
      neonatal nutrition survey.
AB  - OBJECTIVE: The goal of this investigation was to determine how current parenteral
      nutrition and enteral nutrition practice intentions for preterm infants compare
      with published recommendations and previous feeding practices. METHODS: A survey
      of feeding strategies for 3 preterm infant weight groups was sent to NICU
      directors, neonatal fellowship directors, neonatologists, neonatal nurse
      practitioners, and neonatal dieticians. A total of 775 surveys were distributed
      by both electronic and standard mail services. RESULTS: There were 176 survey
      responses (23%). The majority of practitioners initiated parenteral nutrition for
      very preterm infants in the first day of life. Ninety-one percent of respondents
      increased protein delivery daily. Most respondents increased lipid delivery at a
      fixed rate, rather than on the basis of triglyceride levels. Insulin was used in
      98% of units, but only 12% of the time as a nutritional adjuvant to increase
      weight gain. Across all birth weight categories, breast milk was prescribed most
      commonly for the first enteral feeding. Enteral feedings were started earlier and
      increased faster than in the past, especially for extremely low birth weight
      infants (<1000 g). The majority of respondents prescribed enteral feedings for
      infants with indwelling umbilical arterial (75%) and umbilical venous (93%)
      catheters. Despite data that more rapid feeding advancement is safe, >80% of
      respondents increased feedings at rates of 10 to 20 mL/kg per day across all
      weight categories. CONCLUSIONS: Clinicians reported that they are initiating
      parenteral and enteral nutrition earlier and in larger volumes than in the past,
      reflecting increased knowledge about best nutritional practices in very preterm
      neonates. The data suggest that the persistent extrauterine growth failure of
      preterm infants is not attributable to a lack of best nutritional practice
      knowledge and intention.

PMID- 19117862
TI  - Photoisomers: obfuscating factors in clinical peroxidase measurements of unbound
      bilirubin?
AB  - OBJECTIVES: The objectives of the study were to measure the effect of 4Z,15E
      bilirubin on peroxidase free bilirubin measurements and to review the literature
      on this topic. METHODS: 4Z,15E-Bilirubin was generated in situ in serum or serum
      albumin solution through controlled irradiation of isomerically pure 4Z,15Z
      bilirubin IXalpha, under conditions in which the total amount of bilirubin
      remained constant. Reactions were monitored by difference spectroscopy, to ensure
      that solutions were not irradiated beyond the initial photostationary state and
      that concentrations of other isomers were kept to a minimum. Prepared in this
      way, 10% to 25% of the total bilirubin in the final solutions was in the form of
      the 4Z,15E-isomer. Free bilirubin in the solutions was measured with a peroxidase
      method, before and after irradiation. The use of bovine serum albumin as a
      surrogate for human albumin in in vitro studies also was investigated. RESULTS:
      The findings of previous studies are not altogether consistent, with a common
      flaw in several being the failure to measure photoisomer concentrations. For
      bilirubin in serum albumin solution, conversion of approximately 25% of the
      4Z,15Z-isomer to 4Z,15E-bilirubin led to a much smaller decrease (<20%) in the
      apparent free bilirubin concentration; for bilirubin in serum, conversion of
      approximately 15% of the 4Z,15Z-isomer to photoisomers resulted in a much larger
      increase ( approximately 40%). Irradiation of bilirubin in bovine serum albumin
      solution generated a very different array of photoisomers than that observed in
      human albumin solutions. CONCLUSIONS: The effect of photoisomers on the accuracy
      and specificity of free 4Z,15Z-bilirubin measurements remains uncertain. In a
      clinical setting, free bilirubin measurements need to be interpreted with caution
      when samples contain photoisomers. Irradiated bovine albumin solutions of
      isomerically impure bilirubin used in previous studies are poor models for
      investigating the effects of phototherapy in humans and the albumin binding of
      photoisomers.

PMID- 19117863
TI  - An investment in health: anticipating the cost of a usual source of care for
      children.
AB  - OBJECTIVES: Among adults, having a usual source of care has been associated with
      lower health care expenditures primarily through decreased emergency department
      and inpatient expenditures. The extent of this effect among children is unknown.
      We hypothesized that children with a usual source of care would have greater odds
      of having any outpatient expenditures, lower odds of emergency department and
      inpatient expenditures, and lower expenditures overall. PATIENTS AND METHODS:
      Using a 2-part model, we studied expenditures among children < or =17 years of
      age in the 2004 Medical Expenditure Panel Survey (N = 8810). Logistic regression
      was used to assess the relationship between having a usual source of care and the
      odds of having any outpatient, emergency department, and inpatient expenditures,
      and ordinary least-squares regression was used to compare the amount of total,
      outpatient, emergency department, and inpatient expenditures among children with
      and without a usual source of care, controlling for confounders. RESULTS: The
      odds of having any expenditures overall and any outpatient expenditures were 2.42
      and 2.91 times higher among children with a usual source of care than among those
      without a usual source of care. The odds of having any emergency department or
      inpatient visits did not differ between groups. Having a usual source of care was
      associated with higher total expenditures and lower inpatient expenditures.
      CONCLUSIONS: Having a usual source of care is associated with increased odds of
      having any expenditures overall and any outpatient expenditures, higher total
      expenditures, and lower inpatient expenditures. Because emergency department and
      inpatient visits are less common among children than among adults, reductions in
      receipt of such care do not offset the associated increase in total expenditures
      and may not be appropriate indicators of the benefit of having a usual source of
      care among children. Intermediate indicators such as receipt of age-appropriate
      preventive services should be assessed.

PMID- 19117861
TI  - Prolonged duration of initial empirical antibiotic treatment is associated with
      increased rates of necrotizing enterocolitis and death for extremely low birth
      weight infants.
AB  - OBJECTIVES: Our objectives were to identify factors associated with the duration
      of the first antibiotic course initiated in the first 3 postnatal days and to
      assess associations between the duration of the initial antibiotic course and
      subsequent necrotizing enterocolitis or death in extremely low birth weight
      infants with sterile initial postnatal culture results. METHODS: We conducted a
      retrospective cohort analysis of extremely low birth weight infants admitted to
      tertiary centers in 1998-2001. We defined initial empirical antibiotic treatment
      duration as continuous days of antibiotic therapy started in the first 3
      postnatal days with sterile culture results. We used descriptive statistics to
      characterize center practice, bivariate analyses to identify factors associated
      with prolonged empirical antibiotic therapy (> or =5 days), and multivariate
      analyses to evaluate associations between therapy duration, prolonged empirical
      therapy, and subsequent necrotizing enterocolitis or death. RESULTS: Of 5693
      extremely low birth weight infants admitted to 19 centers, 4039 (71%) survived >5
      days, received initial empirical antibiotic treatment, and had sterile initial
      culture results through the first 3 postnatal days. The median therapy duration
      was 5 days (range: 1-36 days); 2147 infants (53%) received prolonged empirical
      therapy (center range: 27%-85%). Infants who received prolonged therapy were less
      mature, had lower Apgar scores, and were more likely to be black. In multivariate
      analyses adjusted for these factors and center, prolonged therapy was associated
      with increased odds of necrotizing enterocolitis or death and of death. Each
      empirical treatment day was associated with increased odds of death, necrotizing
      enterocolitis, and the composite measure of necrotizing enterocolitis or death.
      CONCLUSION: Prolonged initial empirical antibiotic therapy may be associated with
      increased risk of necrotizing enterocolitis or death and should be used with
      caution.

PMID- 19117864
TI  - Thelarche, pubarche, and menarche attainment in children with normal and elevated
      body mass index.
AB  - BACKGROUND: The early onset of puberty may be related to obesity, so there is a
      need to know the prevalence of early pubertal milestones in nonoverweight
      children. OBJECTIVE. We compared attainment of stage 2 breasts, stage 3 (sexual)
      pubic hair, and menarche in the Third National Health and Nutrition Examination
      Survey sample of children with normal BMI with those with excessive BMI (> or
      =85th percentile). DESIGN/METHODS: The ages at which 5%, 50%, and 95% of youth
      had attained key pubertal stages were estimated by probit models. Logit models
      were then fit to compare attainment of these milestones in children of excessive
      and normal BMI. RESULTS: Pubertal signs occurred before 8.0 years of age in <5%
      of the normal-BMI general and non-Hispanic white female population. However,
      pubertal milestones generally appeared earlier in normal-BMI non-Hispanic black
      and Mexican American girls; thelarche occurred before age 8.0 in 12% to 19% of
      these groups, and the 5th percentile for menarche was 0.8 years earlier for non
      Hispanic black than non-Hispanic white subjects. Pubarche was found in < or =3%
      of 8.0-year-old girls with normal BMI of all of these ethnic groups but was
      significantly earlier in minority groups. Pubarche appeared before 10.0 years in
      <2% of normal-BMI boys. Girls with excessive BMI had a significantly higher
      prevalence of breast appearance from ages 8.0 through 9.6 years and pubarche from
      ages 8.0 through 10.2 years than those with normal BMI. Menarche was also
      significantly more likely to occur in preteen girls with an elevated BMI.
      CONCLUSIONS: Prevalence estimates are given for the key pubertal milestones in
      children with normal BMI. Breast and sexual pubic hair development are premature
      before 8 years of age in girls with normal BMI in the general population.
      Adiposity and non-Hispanic black and Mexican American ethnicity are independently
      associated with earlier pubertal development in girls.

PMID- 19117866
TI  - Severe acute respiratory syndrome-associated coronavirus infection in Toronto
      children: a second look.
AB  - OBJECTIVES: During the severe acute respiratory syndrome outbreak of 2003, there
      was an impetus to provide clinical information to the medical community in a
      timely manner. Accordingly, a preliminary report of our experience of suspected
      severe acute respiratory syndrome-associated coronavirus infections in children
      was published without microbiological findings. This report provides an update on
      pediatric severe acute respiratory syndrome-associated coronavirus infections in
      Toronto, Ontario, Canada, that includes microbiological findings. METHODS: All of
      the children admitted to the Hospital for Sick Children between March 14 and June
      15, 2003, with suspect severe acute respiratory syndrome-associated coronavirus
      infection were included. A proven case was defined as one that fulfilled the
      clinical criteria for suspect severe acute respiratory syndrome-associated
      coronavirus infection and demonstrated a serologic response to severe acute
      respiratory syndrome-associated coronavirus. Serology results, from a
      neutralizing antibody assay, were considered positive if the sera inhibited the
      development of a severe acute respiratory syndrome-associated coronavirus
      specific cytopathic effect at a dilution of > or =1:8. RESULTS: Neutralizing
      antibody to severe acute respiratory syndrome-associated coronavirus was
      demonstrated in 8 of 25 children admitted with suspect severe acute respiratory
      syndrome-associated coronavirus infection. In 3 of these 8 children, severe acute
      respiratory syndrome-associated coronavirus was also detected by reverse
      transcription polymerase chain reaction in the stool. All 8 had documented
      exposure to > or =1 severe acute respiratory syndrome-associated coronavirus
      infected adults residing in the same household. Exposure that was limited to
      visiting a Toronto hospital at which severe acute respiratory syndrome-associated
      coronavirus-infected patients were admitted or travel from a country in which
      severe acute respiratory syndrome had been reported did not result in documented
      infection in any of our cases. On the basis of our clinical case definition, 6 of
      8 microbiologically confirmed case had been classified as having probable severe
      acute respiratory syndrome-associated coronavirus infection. Clinical disease was
      mild, nonspecific, and self-limited and was indistinguishable from that reported
      with other common respiratory viruses. CONCLUSIONS: The factor most strongly
      associated with severe acute respiratory syndrome-associated coronavirus
      infection in Toronto children was a history of close contact with an adult severe
      acute respiratory syndrome-associated coronavirus case. This serves to reinforce
      the importance of routinely obtaining a thorough epidemiologic travel and
      exposure history for all subjects with suspected infectious diseases.

PMID- 19117865
TI  - A pilot randomized, controlled trial of later treatment with a peptide
      containing, synthetic surfactant for the prevention of bronchopulmonary
      dysplasia.
AB  - OBJECTIVE: Oxidant injury and lung inflammation in extremely premature infants
      are associated with the development of bronchopulmonary dysplasia. Surfactant
      dysfunction resulting from these events may contribute to the pathogenesis of
      bronchopulmonary dysplasia. Treatment with exogenous surfactant may decrease the
      incidence or severity of bronchopulmonary dysplasia. We conducted a masked,
      multicenter, multinational, randomized, controlled, pilot study to estimate the
      effects of treating infants at high risk for developing bronchopulmonary
      dysplasia with lucinactant, a synthetic, peptide-containing surfactant, on safety
      during dosing and the incidence of death or bronchopulmonary dysplasia. METHODS:
      Preterm infants between 600 and 900 g requiring mechanical ventilation and a
      fraction of inspired oxygen of > or =0.30 between 3 and 10 days of age were
      randomly assigned to receive either sham air (placebo) or 1 of 2 doses of
      lucinactant (90 or 175 mg/kg total phospholipid) every 48 hours to a maximum of 5
      doses, if they remained on mechanical ventilation. RESULTS: Of 136 infants
      enrolled at 34 sites, 44 received placebo, 47 received 90 mg/kg total
      phospholipid, and 45 received 175 mg/kg total phospholipid. The 90 mg/kg group
      had a significantly higher percentage of boys (64%) compared with the placebo
      group (39%); no other significant differences in baseline characteristics among
      groups were present. Compared with placebo, both the 90 mg/kg and 175 mg/kg
      groups experienced a significantly higher incidence of desaturation and
      bradycardia during dosing. Twenty-four hours after dosing, the mean fraction of
      inspired oxygen was lower in both lucinactant groups (33%) compared with the
      placebo group (39%). The incidence of mortality or bronchopulmonary dysplasia was
      66% in the placebo group, 79% in the 90 mg/kg group, and 58% in the 175 mg/kg
      group. These differences were not statistically significant. There were no
      statistical differences among groups for pneumothorax, pulmonary interstitial
      emphysema, intraventricular hemorrhage, periventricular leukomalacia, retinopathy
      of prematurity, or mortality. CONCLUSIONS: There were trends toward lower oxygen
      requirements and toward a lower incidence of mortality or bronchopulmonary
      dysplasia at 36 weeks' postmenstrual age in infants who received the higher dose
      of lucinactant, and this warrants further investigation.

PMID- 19117867
TI  - Growth-curve standards and the assessment of early excess weight gain in infancy.
AB  - OBJECTIVES: Increasing overweight and obesity are growing problems among children
      worldwide. Prevention requires an understanding of when excess weight gain begins
      and the determinants that place children at risk. The aim of our study was to
      illustrate how the growth curve used to assess growth influences the
      interpretation of weight gain and the age of onset of higher weight gains in
      infancy. METHODS: This was a longitudinal study of Canadian infants from birth to
      18 months of age. Infant feeding pattern was recorded monthly, and weight and
      length of 73 infants were measured at 8 different ages. Weight, length, weight
      for length, and BMI z scores were compared with the Centers for Disease Control
      and Prevention 2000 growth curves and World Health Organization growth standard.
      RESULTS: Comparison with the Centers for Disease Control and Prevention growth
      curves showed that Canadian infants grew similarly or slightly slower than their
      US counterparts. Using the World Health Organization growth standard, an increase
      in body weight occurred between 6 and 9 months of age, associated with a change
      from breastfeeding to formula feeding and introduction of solid foods. When
      compared with the World Health Organization standards, breastfed infants followed
      the standards, but formula-fed infants deviated with higher weight for age. When
      compared with the Centers for Disease Control and Prevention charts, breastfed
      infants showed an apparent decline in weight for age beginning at approximately 6
      months. CONCLUSIONS: The choice of growth curve is important to interpreting
      infant growth and identifying the onset of excess weight gain. Identification of
      the prevalence and age of onset of early excess weight gains among Canadian
      infants will be best achieved by using the World Health Organization growth
      standards.

PMID- 19117868
TI  - Perinatal outcomes associated with preterm birth at 33 to 36 weeks' gestation: a
      population-based cohort study.
AB  - OBJECTIVE: The aim of our population-based study was to compare the mortality and
      morbidity of late-preterm infants to those born at term. Advancement in the care
      of extremely preterm infants has led to a shift of focus away from the more
      mature preterms, who are being managed as "near terms" and treated as "near
      normal." Some recent studies have suggested an increased risk of mortality and
      morbidity in this group compared with infants born at term. However, there are
      few population-based mortality and morbidity statistics for this cohort,
      particularly reflecting current practice. METHODS: Using data from the British
      Columbia Perinatal Database Registry we analyzed all singleton births between 33
      and 40 weeks' gestation from April 1999 to March 2002 in the province of British
      Columbia, Canada. We divided this birth cohort into late preterm (33-36 weeks, n
      = 6381) and term (37-40 weeks, n = 88 867) groups. We compared mortality and
      morbidity data and associated maternal factors between the 2 groups. RESULTS:
      Stillbirth rate and perinatal, neonatal, and infant mortality rates were
      significantly higher in the late-preterm group. Infants in this group needed
      resuscitation at birth more frequently than those in the term group. Late-preterm
      infants had a significantly higher incidence of respiratory morbidity and
      infection and had a significantly longer duration of hospital stay. Maternal
      factors that were more common in the late-preterm group included
      chorioamnionitis, hypertension, diabetes, thrombophilia, prelabor rupture of
      membranes, primigravida, and teenage pregnancy. CONCLUSIONS: Our data support
      recent literature regarding neonatal mortality and morbidity in late-preterm
      infants and warrants a review of care for this group at the local, national, and
      global levels. Reorganization of services and increased resource allocation may
      be needed in most hospitals and community settings to achieve optimization of
      care for this group of infants.

PMID- 19117869
TI  - Sport-related concussion.
AB  - Sport-related concussion is a common injury in children and adolescents. Athletes
      seldom report concussive symptoms, which makes the diagnosis a challenge. The
      management of sport-related concussion has changed significantly over the last
      several years. The previously used grading systems and return-to-play guidelines
      have been abandoned in favor of more individualized assessment and management.
      Neuropsychological testing is being used more frequently to assist in management.
      After recovery, it is recommended that an athlete's return-to-play progress in a
      gradual, stepwise fashion while being monitored by a health care provider. Proper
      assessment and management of a sport-related concussion is crucial, because
      repeat concussions can result in decreased neurocognitive functioning, increased
      symptomatology, and, at times, catastrophic outcomes.

PMID- 19117870
TI  - Neurofibromatosis type 1 revisited.
AB  - Neurofibromatosis type 1 (NF1) is an autosomal dominant condition with a
      worldwide incidence of approximately 1 per 2500 to 3000 individuals. Caused by a
      germ-line-inactivating mutation in the NF1 gene on chromosome 17, the disease is
      associated with increased morbidity and mortality. In the past several years,
      significant progress has been made in standardizing management of the major
      clinical features of neurofibromatosis type 1. Moreover, improved understanding
      of how the neurofibromatosis type 1 protein, neurofibromin, regulates cell growth
      recently provided insight into the pathogenesis of the disease and has led to the
      development of new therapies. In this review, we describe the clinical
      manifestations, recent molecular and genetic findings, and current and developing
      therapies for managing clinical problems associated with neurofibromatosis type
      1.

PMID- 19117871
TI  - The Pediatric AIDS Corps: responding to the African HIV/AIDS health professional
      resource crisis.
AB  - Health professional capacity for delivery of HIV/AIDS care and treatment is
      severely constrained across sub-Saharan Africa. African health professional
      expertise in pediatrics is in particularly short supply. Here we describe a
      Pediatric AIDS Corps program that was designed to place pediatricians and other
      physicians in Africa on a long-term basis to expand existing health professional
      capacity for pediatric and family HIV/AIDS care and treatment. In the first 2
      years of this program, 76 physicians were placed in 5 African countries that have
      been hit hard by HIV/AIDS. Enrollment of HIV-infected children in care more than
      quadrupled over a 24-month period, to 26 590. We believe that this pilot program
      can serve as a model for larger-scale efforts to immediately expand access for
      African children and families to life-saving HIV/AIDS care and treatment.

PMID- 19117872
TI  - Very early surfactant without mandatory ventilation in premature infants treated
      with early continuous positive airway pressure: a randomized, controlled trial.
AB  - BACKGROUND: Chronic lung disease is one of the most frequent and serious
      complications of premature birth. Because mechanical ventilation is a major risk
      factor for chronic lung disease, the early application of nasal continuous
      positive airway pressure has been used as a strategy for avoiding mechanical
      ventilation in premature infants. Surfactant therapy improves the short-term
      respiratory status of premature infants, but its use is traditionally limited to
      infants being mechanically ventilated. Administration of very early surfactant
      during a brief period of intubation to infants treated with nasal continuous
      positive airway pressure may improve their outcome and further decrease the need
      for mechanical ventilation. OBJECTIVE: Our goal was to determine if very early
      surfactant therapy without mandatory ventilation improves outcome and decreases
      the need for mechanical ventilation when used in very premature infants treated
      with nasal continuous positive airway pressure soon after birth. DESIGN/METHODS:
      Eight centers in Colombia participated in this randomized, controlled trial.
      Infants born between 27 and 31 weeks' gestation with evidence of respiratory
      distress and treated with supplemental oxygen in the delivery room were randomly
      assigned within the first hour of life to intubation, very early surfactant,
      extubation, and nasal continuous positive airway pressure (treatment group) or
      nasal continuous airway pressure alone (control group). The primary outcome was
      the need for subsequent mechanical ventilation using predefined criteria.
      RESULTS: From January 1, 2004, to December 31, 2006, 279 infants were randomly
      assigned, 141 to the treatment group and 138 to the control group. The need for
      mechanical ventilation was lower in the treatment group (26%) compared with the
      control group (39%). Air-leak syndrome occurred less frequently in the treatment
      group (2%) compared with the control group (9%). The percentage of patients
      receiving surfactant after the first hour of life was also significantly less in
      the treatment group (12%) compared with the control group (26%). The incidence of
      chronic lung disease (oxygen treatment at 36 weeks' postmenstrual age) was 49% in
      the treatment group compared with 59% in the control group. All other outcomes,
      including mortality, intraventricular hemorrhage, and periventricular
      leukomalacia were similar between the groups. CONCLUSIONS: In premature infants
      treated with nasal continuous positive airway pressure early after birth, the
      addition of very early surfactant therapy without mandatory ventilation decreased
      the need for subsequent mechanical ventilation, decreased the incidence of air
      leak syndrome, and seemed to be safe. Reduction in the need for mechanical
      ventilation is an important outcome when medical resources are limited and may
      result in less chronic lung disease in both developed and developing countries.

PMID- 19117873
TI  - Chronic diarrhea and juvenile cataracts: think cerebrotendinous xanthomatosis and
      treat.
AB  - Cerebrotendinous xanthomatosis is an autosomal recessive disease of bile acid
      synthesis caused by 27-hydroxylase deficiency. Treatment with chenodeoxycholic
      acid normalizes cholestanol concentrations and abrogates progression of the
      disease. We present 4 patients with cerebrotendinous xanthomatosis within 1
      family who were treated with chenodeoxycholic acid for 14 years. Two young
      sisters started treatment at the preclinical stage before the appearance of major
      symptoms. Their 2 older uncles, who had already developed the complete phenotypic
      form of cerebrotendinous xanthomatosis when diagnosed, commenced treatment at the
      same time as the sisters, thus establishing a natural control group. After 14
      years of chenodeoxycholic acid therapy, the cholestanol levels of all 4 patients
      decreased to normal levels (<6 microg/mL). Both sisters remained asymptomatic.
      Only moderate improvement in symptoms was observed in their uncles. In this long
      term study, prompt preclinical administration of chenodeoxycholic acid in early
      childhood completely prevented the cerebrotendinous xanthomatosis phenotype in 2
      sisters. Pediatricians should be aware of this diagnostic possibility of
      cerebrotendinous xanthomatosis in children presenting with chronic diarrhea and
      juvenile cataracts. Prevention is particularly significant in light of the
      availability of early genetic diagnosis and the devastating effects of this
      illness if not treated.

PMID- 19117874
TI  - Looking back on 34 years of the journal: 1974-20??

PMID- 19117875
TI  - Editorial transitions: continuing to build on the strong foundation of our
      predecessors.

PMID- 19117876
TI  - Pediatrics launches redesign of Web site.

PMID- 19117877
TI  - The global problem of injuries to children and adolescents.

PMID- 19117878
TI  - Blood gas values during hypothermia in asphyxiated term neonates.

PMID- 19117879
TI  - 21st-century use for surfactant?

PMID- 19117880
TI  - Evaluation and management of the infant exposed to HIV-1 in the United States.
AB  - The pediatrician plays a key role in the prevention of mother-to-child
      transmission of HIV-1 infection. For infants born to women with HIV-1 infection
      identified during pregnancy, the pediatrician ensures that antiretroviral
      prophylaxis is provided to the infant to decrease the risk of acquiring HIV-1
      infection and promotes avoidance of postnatal HIV-1 transmission by advising HIV
      1-infected women not to breastfeed. The pediatrician should perform HIV-1
      antibody testing for infants born to women whose HIV-1 infection status was not
      determined during pregnancy or labor. For HIV-1-exposed infants, the pediatrician
      monitors the infant for early determination of HIV-1 infection status and for
      possible short- and long-term toxicity from antiretroviral exposures. Provision
      of chemoprophylaxis for Pneumocystis jiroveci pneumonia and support of families
      living with HIV-1 by providing counseling to parents or caregivers are also
      important components of care.

PMID- 19117881
TI  - Recommended childhood and adolescent immunization schedules--United States, 2009.

PMID- 19117882
TI  - Underinsurance of adolescents: recommendations for improved coverage of
      preventive, reproductive, and behavioral health care services.
AB  - The purpose of this policy statement is to address the serious underinsurance
      (ie, insurance that exists but is inadequate) problems affecting insured
      adolescents' access to needed preventive, reproductive, and behavioral health
      care. In addition, the statement addresses provider payment problems that
      disproportionately affect clinicians who care for adolescents. Among adolescents
      with insurance, particularly private health insurance, coverage of needed
      services is often inadequate. Benefits are typically limited in scope and amount;
      certain diagnoses are often excluded; and cost-sharing requirements are often too
      high. As a result, underinsurance represents a substantial problem among
      adolescents and adversely affects their health and well-being. In addition to
      underinsurance problems, payment problems in the form of inadequate payment,
      uncompensated care for confidential reproductive services, and the failure of
      insurers to recognize and pay for certain billing and diagnostic codes are
      widespread among both private and public insurers. Payment problems negatively
      affect clinicians' ability to offer needed services to adolescents, especially
      publicly insured adolescents.

PMID- 19117883
TI  - Family burden after traumatic brain injury in children.
AB  - OBJECTIVE: Traumatic brain injury has a substantial impact on caregivers. This
      study describes the burden experienced by caregivers of children with traumatic
      brain injury and examines the relationship between child functioning and family
      burden during the first year after injury. PATIENTS AND METHODS: Children aged 5
      to 15 years hospitalized for traumatic brain injury at 4 participating trauma
      centers were eligible. Caregivers completed baseline and 3- and 12-month
      telephone interviews measuring the child's health-related quality of life using
      the Pediatric Quality of Life Inventory. The emotional impact scale of the Child
      Health Questionnaire was used to identify caregivers with substantial distress,
      including general worry or interference with family routine. Caregiver
      perceptions of whether health care needs were met or unmet and days missed from
      work were also measured. RESULTS: A total of 330 subjects enrolled; follow-up was
      conducted with 312 at 3 months and 288 at 12 months. Most subjects were white
      (68%) and male (69%). Abnormal Pediatric Quality of Life Inventory subscores were
      related to substantial caregiver burden (either general worry or interference in
      routine). These abnormalities were reported by >75% of patients at 3 months and
      persisted to 1 year in some patients. Parental perception of unmet health care
      needs was strongly related to family burden outcomes, with up to 69% of this
      subset of parents reporting substantial worry, and nearly one quarter reporting
      interference with daily routine/concentration 1 year after injury. Child
      dysfunction predicted parental burden at 3 and 12 months. Burden was greater when
      health care need was unmet. Abnormalities on the Pediatric Quality of Life
      Inventory predicted the amount of work missed by parents, especially in the
      presence of unmet needs. CONCLUSIONS: Caregivers are more likely to report family
      burden problems when child functioning is poorer and health care needs are unmet.
      Improved identification and provision of services is a potentially modifiable
      factor that may decrease family burden after pediatric traumatic brain injury.

PMID- 19117884
TI  - Neurodevelopmental outcome of extremely low birth weight infants randomly
      assigned to restrictive or liberal hemoglobin thresholds for blood transfusion.
AB  - BACKGROUND AND OBJECTIVE: Extremely low birth weight infants frequently receive
      red cell transfusions. We sought to determine whether a restrictive versus
      liberal hemoglobin transfusion threshold results in differences in death or
      adverse neurodevelopmental outcomes of extremely low birth weight infants.
      PATIENTS AND METHODS: Extremely low birth weight infants previously enrolled in
      the Preterm Infants in Need of Transfusion Trial, a randomized, controlled trial
      of low versus high hemoglobin transfusion thresholds, were followed up at 18 to
      21 months' corrected age. Erythrocyte transfusion was determined by an algorithm
      of low (restrictive) or high (liberal) hemoglobin transfusion thresholds,
      differing by 10 to 20 g/L and maintained until first hospital discharge. The
      primary composite outcome was death or the presence of cerebral palsy, cognitive
      delay, or severe visual or hearing impairment. RESULTS: Of 451 enrolled infants,
      the primary outcome was available in 430. There was no statistically significant
      difference in the primary outcome, found in 94 (45%) of 208 in the restrictive
      group and 82 (38%) of 213 in the liberal group. There were no statistically
      significant differences in preplanned secondary outcomes. However, the difference
      in cognitive delay (Mental Development Index score < 70) approached statistical
      significance. A posthoc analysis with cognitive delay redefined (Mental
      Development Index score < 85) showed a significant difference favoring the
      liberal threshold group. CONCLUSIONS: Maintaining the hemoglobin of extremely low
      birth weight infants at these restrictive rather than liberal transfusion
      thresholds did not result in a statistically significant difference in combined
      death or severe adverse neurodevelopmental outcome.

PMID- 19117885
TI  - Reversal of type 2 diabetes mellitus and improvements in cardiovascular risk
      factors after surgical weight loss in adolescents.
AB  - OBJECTIVES: Type 2 diabetes mellitus is associated with obesity, dyslipidemia,
      and hypertension, all well-known risk factors for cardiovascular disease.
      Surgical weight loss has resulted in a marked reduction of these risk factors in
      adults. We hypothesized that gastric bypass would improve parameters of metabolic
      dysfunction and cardiovascular risk in adolescents with type 2 diabetes mellitus.
      PATIENTS AND METHODS: Eleven adolescents who underwent Roux-en-Y gastric bypass
      at 5 centers were included. Anthropometric, hemodynamic, and biochemical measures
      and surgical complications were analyzed. Similar measures from 67 adolescents
      with type 2 diabetes mellitus who were treated medically for 1 year were also
      analyzed. RESULTS: Adolescents who underwent Roux-en-Y gastric bypass were
      extremely obese (mean BMI of 50 +/- 5.9 kg/m(2)) with numerous cardiovascular
      risk factors. After surgery there was evidence of remission of type 2 diabetes
      mellitus in all but 1 patient. Significant improvements in BMI (-34%), fasting
      blood glucose (-41%), fasting insulin concentrations (-81%), hemoglobin A1c
      levels (7.3%-5.6%), and insulin sensitivity were also seen. There were
      significant improvements in serum lipid levels and blood pressure. In comparison,
      adolescents with type 2 diabetes mellitus who were followed during 1 year of
      medical treatment demonstrated stable body weight (baseline BMI: 35 +/- 7.3
      kg/m(2); 1-year BMI: 34.9 +/- 7.2 kg/m(2)) and no significant change in blood
      pressure or in diabetic medication use. Medically managed patients had
      significantly improved hemoglobin A1c levels over 1 year (baseline: 7.85% +/-
      2.3%; 1 year: 7.1% +/- 2%). CONCLUSIONS: Extremely obese diabetic adolescents
      experience significant weight loss and remission of type 2 diabetes mellitus
      after Roux-en-Y gastric bypass. Improvements in insulin resistance, beta-cell
      function, and cardiovascular risk factors support Roux-en-Y gastric bypass as an
      intervention that improves the health of these adolescents. Although the long
      term efficacy of Roux-en-Y gastric bypass is not known, these findings suggest
      that Roux-en-Y gastric bypass is an effective option for the treatment of
      extremely obese adolescents with type 2 diabetes mellitus.

PMID- 19117886
TI  - Using telemedicine to improve the care delivered to sexually abused children in
      rural, underserved hospitals.
AB  - OBJECTIVE: We used live telemedicine consultations to assist remote providers in
      the examination of sexually assaulted children presenting to rural, underserved
      hospitals. We hypothesized that telemedicine would increase the ability of the
      rural provider to perform a complete and accurate sexual assault examination.
      PATIENTS AND METHODS: Child abuse experts from a university children's hospital
      provided 24/7 live telemedicine consultations to clinicians at 2 rural,
      underserved hospitals. Consultations consisted of videoconferencing to assist in
      the examination and interpretation of findings during live examinations.
      Consecutive female patients <18 years of age presenting to the 2 participating
      hospitals were included. We developed and used an instrument to assess the
      quality of care and the interventions provided via telemedicine as it related to
      patient history, physical examination, colposcopic and manual manipulation
      techniques, interpretation of findings, and treatment plans for victims of child
      sexual abuse. RESULTS: Data from 42 live telemedicine consultations were
      analyzed. The mean duration of the consultations was 71 minutes (range: 25-210
      minutes). The consultations resulted in changes in interview methods (47%), the
      use of the multimethod examination technique (86%), and the use of adjunct
      techniques (40%). There were 9 acute sexual assault telemedicine consults that
      resulted in changes to the collection of forensic evidence (89%). Rankings of
      practitioners' skills and the telemedicine consult effectiveness were high, with
      the majority of cases scoring > or =5 on a 7-point Likert scale. CONCLUSIONS: The
      use of telemedicine to assist in the examination of sexually assaulted children
      presenting to underserved, rural communities results in significant changes in
      the methods of examination and evidence collection. It is possible that this
      model of care results in increased quality of care and appropriate forensic
      evidence collection.

PMID- 19117887
TI  - Long-term efficacy and safety of laronidase in the treatment of
      mucopolysaccharidosis I.
AB  - OBJECTIVE: Our goal was to evaluate the long-term safety and efficacy of
      recombinant human alpha-l-iduronidase (laronidase) in patients with
      mucopolysaccharidosis I. PATIENTS AND METHODS: All 45 patients who completed a 26
      week, double-blind, placebo-controlled trial of laronidase were enrolled in a 3.5
      year open-label extension study. Mean patient age at baseline was 16 (range: 6
      43) years. All patients had attenuated disease (84% Hurler-Scheie, 16% Scheie
      phenotypes). Clinical, biochemical, and health outcomes measures were evaluated
      through the extension phase. Changes are presented as the mean +/- SEM. RESULTS:
      All 40 patients (89%) who completed the trial received at least 80% of scheduled
      infusions. As shown in earlier trials, urinary glycosaminoglycan levels decreased
      within the first 12 weeks and liver volume decreased within the first year.
      Percent predicted forced vital capacity remained stable, with a linear slope of 
      0.78 percentage points per year. The 6-minute walk distance increased 31.7 +/-
      10.2 m in the first 2 years, with a final gain of 17.1 +/- 16.8 m. Improvements
      in the apnea/hypopnea index (decrease of 7.6 +/- 4.5 events per hour among the
      patients with significant baseline sleep apnea) and shoulder flexion (increase of
      17.4 degrees +/- 3.6 degrees) were most rapid during the first 2 years.
      Improvements in the Child Health Assessment Questionnaire/Health Assessment
      Questionnaire disability index (decrease of 0.31 +/- 0.11, signifying a
      clinically meaningful improvement in activities of daily living) were gradual and
      sustained over the treatment period. Laronidase infusions were generally well
      tolerated except in 1 patient who experienced an anaphylactic reaction. Infusion
      associated reactions, which occurred in 53% of the patients, were mostly mild,
      easily managed, and decreased markedly after 6 months. One patient died as a
      result of an upper respiratory infection unrelated to treatment. Antibodies to
      laronidase developed in 93% of the patients; 29% of the patients were
      seronegative at their last assessment. CONCLUSIONS: This trial demonstrates the
      long-term clinical benefit and safety of laronidase in attenuated patients with
      mucopolysaccharidosis I and highlights the magnitude and chronology of treatment
      effects. Prompt diagnosis and early treatment will maximize treatment outcomes.

PMID- 19117888
TI  - Improving early relationships: a randomized, controlled trial of an age-paced
      parenting newsletter.
AB  - OBJECTIVES: Parenting is recognized as a key mediator in both health and
      educational outcomes. Much is known on the value of support and group work in
      benefiting parenting, but little is known on the effect of written information. A
      randomized, controlled trial was conducted to evaluate the effect of a parenting
      newsletter, sent monthly to the parents' home from birth to 1 year, on maternal
      well-being and parenting style. We tested the hypothesis that mothers receiving
      the newsletter would show less stress and better parenting characteristics than
      controls. METHODS: Parents of first infants born in a North East England District
      General Hospital between February and October 2003 who consented to take part in
      the study were randomly allocated to either the intervention or control arm.
      Those in the intervention arm were sent 12 monthly issues of an age-paced
      parenting newsletter containing information on emotional development, parent
      child interaction, and play. Both the intervention and control group received
      normal parenting support. Mothers in both groups completed the Well-being Index,
      Parenting Daily Hassles Scale, and the Adult-Adolescent Parenting Inventory at
      birth and at 1 year. RESULTS: One hundred eighty-five mothers were recruited,
      with 94 randomly assigned to the intervention group, and 91 controls. Allowing
      for differences at recruitment, there were significant differences between the
      groups at 1 year: the intervention mothers had lower frequency and intensity of
      perceived hassles and fewer inappropriate expectations of the infant on the Adult
      Adolescent Parenting Inventory than the control mothers. CONCLUSIONS: A monthly
      parenting newsletter sent directly to the home in the first year of life seems to
      help parents to understand their infant better and feel less hassled. This
      intervention is low cost and can be applied to all parents, so it is
      nonstigmatizing.

PMID- 19117889
TI  - Attention-deficit/hyperactivity disorder: how much responsibility are
      pediatricians taking?
AB  - BACKGROUND: Attention-deficit/hyperactivity disorder, the most common childhood
      behavioral condition, is one that pediatricians think they should identify and
      treat/manage. OBJECTIVE: Our goals were to explore the relationships between
      pediatricians' self-reports of their practice behaviors concerning usually
      inquiring about and treating/managing attention-deficit/hyperactivity disorder
      and (1) attitudes regarding perceived responsibility for attention
      deficit/hyperactivity disorder and (2) personal and practice characteristics.
      METHODS: We analyzed data from the 59th Periodic Survey of the American Academy
      of Pediatrics for the 447 respondents who practice exclusively in general
      pediatrics. Bivariate and logistic regression analyses were used to identify
      attitudes and personal and practice characteristics associated with usually
      identifying and treating/managing attention-deficit/hyperactivity disorder.
      RESULTS: A total of 67% reported that they usually inquire about and 65% reported
      that they usually treat/manage attention-deficit/hyperactivity disorder. Factors
      positively associated with usually inquiring about attention
      deficit/hyperactivity disorder in adjusted multivariable analyses include
      perceived high prevalence among current patients, attendance at a
      lecture/conference on child mental health in the past 2 years, having patients
      who are assigned or can select a specific pediatrician, practicing in suburban
      communities, practicing for > or =10 years, and being female. Pediatricians'
      attitudes about responsibility for identification of attention
      deficit/hyperactivity disorder were not associated with usually inquiring about
      attention-deficit/hyperactivity disorder in either unadjusted or adjusted
      analyses. Attitudes about treating/managing attention-deficit/hyperactivity
      disorder were significantly associated with usually treating/managing attention
      deficit/hyperactivity disorder in unadjusted and adjusted analyses. Those who
      perceived that pediatricians should be responsible for treating/managing had
      almost 12 times the odds of reporting treating/managing attention
      deficit/hyperactivity disorder, whereas those who believe physicians should refer
      had threefold decreased odds of treating/managing. Other physician/practice
      characteristics significantly associated with the odds of usually
      treating/managing attention-deficit/hyperactivity disorder include belief that
      attention-deficit/hyperactivity disorder is very prevalent among current
      patients, seeing patients who are assigned or can select a specific pediatrician,
      and practice location. CONCLUSIONS: Taking responsibility for treating attention
      deficit/hyperactivity disorder and practice characteristics seem to be important
      correlates of pediatrician self-reported behavior toward caring for children with
      attention-deficit/hyperactivity disorder.

PMID- 19117890
TI  - Has prenatal screening influenced the prevalence of comorbidities associated with
      Down syndrome and subsequent survival rates?
AB  - OBJECTIVES: With this study we aimed to compare survival rates for children with
      Down syndrome in 2 time periods, 1 before prenatal screening (1988-1990) and 1
      contemporaneous with screening (1998-2000), and to examine the frequency of
      comorbidities and their influence on survival rates. METHODS: Record-linkage was
      performed between the population-based Victorian Birth Defects Register and
      records of deaths in children up to 15 years of age collected under the auspice
      of the Consultative Council on Obstetric and Pediatric Mortality and Morbidity.
      Cases of Down syndrome were coded according to the presence or absence of
      comorbidities by using the International Classification of Diseases, Ninth
      Revision classification of birth defects. Kaplan-Meier survival functions and log
      rank tests for equality of survival distributions were performed. RESULTS: Of
      infants liveborn with Down syndrome in 1998-2000, 90% survived to 5 years of age,
      compared with 86% in the earlier cohort. With fetal deaths excluded, the
      proportion of isolated Down syndrome cases in the earlier cohort was 48.7%
      compared with 46.1% in the most recent cohort. In 1988-1990 there was at least 1
      cardiac defect in 41.1% of cases and in 45.4% in 1998-2000. There was significant
      variation in survival rates for the different comorbidity groupings in the 1988
      1990 cohort, but this was not so evident in the 1998-2000 cohort. CONCLUSIONS:
      Survival of children with Down syndrome continues to improve, and there is an
      overall survival figure of 90% to at least 5 years of age. It is clear from this
      study that prenatal screening technologies are not differentially ascertaining
      fetuses with Down syndrome and additional defects, because there has been no
      proportional increase in births of isolated cases with Down syndrome.

PMID- 19117891
TI  - Cost-effectiveness of early treatment for retinopathy of prematurity.
AB  - BACKGROUND: The Early Treatment for Retinopathy of Prematurity trial demonstrated
      that peripheral retinal ablation of eyes with high-risk prethreshold retinopathy
      of prematurity (early treatment) is associated with improved visual outcomes at 9
      months' corrected gestational age compared with treatment at threshold disease
      (conventional management). However, early treatment increased the frequency of
      laser therapy, anesthesia with intubation, treatment-related systemic
      complications, and the need for repeat treatments. OBJECTIVE: To determine the
      cost-effectiveness of an early treatment strategy for retinopathy of prematurity
      compared with conventional management. DESIGN/METHODS: We developed a stochastic
      decision analytic model to assess the incremental cost of early treatment per eye
      with severe visual impairment prevented. We derived resource-use and efficacy
      estimates from the Early Treatment for Retinopathy of Prematurity trial's
      published outcome data. We used a third-party payer perspective. Our primary
      analysis focused on outcomes from birth through 9 months' corrected gestational
      age. A secondary analysis used a lifetime horizon. Parameter uncertainty was
      quantified by using probabilistic and deterministic sensitivity analyses.
      RESULTS: The incremental cost-effectiveness of early treatment was $14,200 per
      eye with severe visual impairment prevented. There was a 90% probability that the
      cost-effectiveness of early treatment would be less than $40,000 per eye with
      severe visual impairment prevented and a 0.5% probability that early treatment
      would be cost-saving (less costly and more effective). Limiting early treatment
      to more severely affected eyes (eyes with "type 1 retinopathy of prematurity" as
      defined by the Early Treatment for Retinopathy of Prematurity trial) had a cost
      effectiveness of $6,200 per eye with severe visual impairment prevented. Analyses
      that considered long-term costs and outcomes found that early treatment was cost
      saving. CONCLUSIONS: Early treatment of retinopathy of prematurity is both
      efficacious and economically desirable. Because of the high lifetime costs of
      severe visual impairment, the early treatment strategy provides long-term cost
      savings.

PMID- 19117892
TI  - Predicting stuttering onset by the age of 3 years: a prospective, community
      cohort study.
AB  - OBJECTIVES: Our goals were to document (1) the onset of stuttering and (2)
      whether specific child, family, or environmental factors predict stuttering onset
      in children aged up to 3 years. METHODS: Participants included a community
      ascertained cohort of 1619 2-year-old Australian children recruited at 8 months
      of age to study the longitudinal development of early language. The main outcome
      measure was parental telephone report of stuttering onset, verified by face-to
      face expert diagnosis. Preonset continuous measures of the child's temperament
      (approach/withdrawal) and language development were available. Information on a
      range of predictor measures hypothesized to be associated with stuttering onset
      was obtained (maternal mental health and education levels, gender, premature
      birth status, birth weight, birth order, twinning, socioeconomic status, family
      history of stuttering). RESULTS: By 3 years of age, the cumulative incidence of
      stuttering onset was 8.5%. Onset often occurred suddenly over 1 to 3 days (49.6%)
      and involved the use of word combinations (97.1%). Children who stuttered were
      not more shy or withdrawn. Male gender, twin birth status, higher vocabulary
      scores at 2 years of age, and high maternal education were associated with
      stuttering onset. The multivariable model, however, had low predictive strength;
      just 3.7% of the total variation in stuttering onset was accounted for.
      CONCLUSIONS: The cumulative incidence of stuttering onset was much higher than
      reported previously. The hypothesized risk factors for stuttering onset together
      explained little of the variation in stuttering onset up to 3 years of age. Early
      onset was not associated with language delay, social and environmental factors,
      or preonset shyness/withdrawal. Health professionals can reassure parents that
      onset is not unusual up to 3 years of age and seems to be associated with rapid
      growth in language development.

PMID- 19117893
TI  - Platelet transfusion practices among neonatologists in the United States and
      Canada: results of a survey.
AB  - OBJECTIVE: In the absence of scientific evidence, current neonatal platelet
      transfusion practices are based on physicians' preferences, expert advice, or
      consensus-driven recommendations. We hypothesized that there would be significant
      diversity in platelet transfusion triggers, product selection, and dosing among
      neonatologists in the United States and Canada. METHODS: A Web-based survey on
      neonatal platelet transfusion practices was distributed to all members of the
      American Academy of Pediatrics Perinatal Section in the United States and to all
      physicians listed in the 2005 Canadian Neonatology Directory. RESULTS: The
      overall response rate was 37% (1060 of 2875). In the United States, 37% (1007 of
      2700) responded, of which 52% practiced at academic centers. Thirty percent (53
      of 175) of Canadians responded, of whom 94% practiced at academic centers. As
      hypothesized, there was significant practice diversity in both countries. The
      survey also revealed that platelet transfusions are frequently administered to
      nonbleeding neonates with platelet counts of >50 x 10(9)/L. This practice is
      particularly prevalent among neonates with specific clinical conditions,
      including indomethacin treatment, preceding procedures, in the postoperative
      period, or with intraventricular hemorrhages. CONCLUSIONS: There is great
      variability in platelet transfusion practices among US and Canadian
      neonatologists, suggesting clinical equipoise in many clinical scenarios.
      Prospective randomized clinical trials to generate evidence-based neonatal
      platelet transfusion guidelines are needed.

PMID- 19117894
TI  - How well can hospital readmission be predicted in a cohort of hospitalized
      children? A retrospective, multicenter study.
AB  - BACKGROUND: Children with complex chronic conditions depend on both their
      families and systems of pediatric health care, social services, and financing.
      Investigations into the workings of this ecology of care would be advanced by
      more accurate methods of population-level predictions of the likelihood for
      future hospitalization. METHODS: This was a retrospective cohort study. Hospital
      administrative data were collected from 38 children's hospitals in the United
      States for the years 2003-2005. Participants included patients between 2 and 18
      years of age discharged from an index hospitalization during 2004. Patient
      characteristics documented during the index hospitalization or any previous
      hospitalization during the preceding 365 days were included. The main outcome
      measure was readmission to the hospital during the 365 days after discharge from
      the index admission. RESULTS: Among the cohort composed of 186856 patients
      discharged from the participating hospitals during 2004, the mean age was 9.2
      years, with 54.4% male and 52.9% identified as non-Hispanic white. A total of
      17.4% were admitted during the previous 365 days, and among those discharged
      alive (0.6% died during the admission), 16.7% were readmitted during the ensuing
      365 days. The final readmission model exhibited a c statistic of 0.81 across all
      hospitals, with a range from 0.76 to 0.84 for each hospital. Bootstrap-based
      assessments demonstrated the stability of the final model. CONCLUSIONS: Accurate
      population-level prediction of hospital readmissions is possible, and the
      resulting predicted probability of hospital readmission may prove useful for
      health services research and planning.

PMID- 19117895
TI  - Functional magnetic resonance imaging of the sensorimotor system in preterm
      infants.
AB  - OBJECTIVE: Preterm birth at <32 weeks' gestational age has a specific
      predilection for periventricular white matter injury. Early prediction of
      concomitant motor sequelae is a fundamental clinical issue. Recently, functional
      MRI was introduced as a noninvasive method for investigating the functional
      integrity of the neonatal brain. We aimed at implementing a unilateral passive
      forearm extension/flexion functional MRI paradigm in a routine clinical MRI setup
      to allow noninvasive mapping of the sensorimotor system in preterm infants and to
      relate the functional data to structural and behavioral data. PATIENTS AND
      METHODS: Eight patients (median gestational age: 26.5 weeks; median birth weight:
      885 g) were included. The functional MRI was performed at term-equivalent age
      (median: 39 weeks' postconceptional age) under chloral hydrate (50 mg/kg)
      sedation. In 5 of 8 patients, functional MRI data acquisition was successful.
      This resulted in 10 functional data sets (5 for passive stimulation of each
      forearm). RESULTS: Unilateral stimulation was associated with mainly bilateral
      activation of the primary sensorimotor cortex (n = 7 of 10 data sets), the
      prevailing hemodynamic response being a negative blood oxygenation level
      dependent signal. Positive blood oxygenation level-dependent response or failure
      to activate the sensorimotor cortex (n = 3 of 10 data sets) were seen in those
      patients with aberrant structural/behavioral indices. CONCLUSIONS: Our data show
      the feasibility of passive unilateral sensorimotor stimulation during neonatal
      clinical MRI protocols. The bilateral activation pattern observed at this age is
      compatible with a bilaterally distributed sensorimotor system. Our data validate
      initial accounts for a raised incidence of negative blood oxygenation level
      dependent responses in the primary sensorimotor cortex at this developmental
      stage. The negative blood oxygenation level-dependent response is likely to
      reflect a reduction of the oxy/deoxy-hemoglobin ratio during a maturational stage
      characterized by rapid formation of synapses, yet ineffective processing.
      Positive blood oxygenation level-dependent responses or failure to activate the
      sensorimotor cortex may be an early indicator of abnormal development and will
      have to be followed up carefully.

PMID- 19117896
TI  - Safety and immunogenicity of a pentavalent vaccine compared with separate
      administration of licensed equivalent vaccines in US infants and toddlers and
      persistence of antibodies before a preschool booster dose: a randomized, clinical
      trial.
AB  - OBJECTIVE: Our goal was to compare the safety and immunogenicity of a combination
      vaccine (DTaP(5)-IPV-Hib; Pentacel) with that of its separately administered, US
      licensed equivalent vaccines (diphtheria, tetanus, 5-component acellular
      pertussis vaccine [DTaP(5); Daptacel], inactivated poliovirus vaccine [IPV;
      IPOL], and Haemophilus influenzae type b [Hib] vaccine [ActHIB]), when
      administered to infants and toddlers concomitantly with other routinely
      recommended vaccines and to assess antibody persistence from the fourth dose in
      toddlers to the fifth (preschool) DTaP(5) dose. SUBJECTS AND METHODS: In this
      randomized, multicenter study, 1939 healthy infants were immunized at 2, 4, and 6
      months of age with 1 of 3 lots of DTaP(5) coadministered with IPV and Hib
      vaccines or 1 lot of DTaP(5)-IPV-Hib combination vaccine. Subsequently, 849 of
      these study participants were given a fourth dose of DTaP(5) and Hib vaccines or
      a fourth dose of DTaP(5)-IPV-Hib at 1 to 16 months of age. Safety was monitored
      throughout the study, and blood specimens were obtained to assess antibody
      responses. RESULTS: DTaP(5)-IPV-Hib elicited similar or fewer solicited injection
      site and systemic reactions as compared with the separate administration of US
      licensed DTaP(5), IPV, and Hib vaccines. Seroresponse and seroprotection rates
      elicited by DTaP(5)-IPV-Hib were noninferior to US-licensed equivalent vaccines
      after the infant series and after the fourth dose. Children immunized with
      DTaP(5)-IPV-Hib had higher antibody geometric mean concentrations to pertussis
      toxoid and filamentous hemagglutinin; children immunized with the separate
      vaccines had higher responses to pertactin. Hib antibody responses to Hib
      polysaccharide were nearly identical in the DTaP(5)-IPV-Hib and separate-vaccine
      groups. Persistence of antibodies to the fifth (preschool) dose was also similar
      between groups. CONCLUSIONS: DTaP(5)-IPV-Hib combination vaccine was shown to be
      immunogenic and well tolerated. No clinically important differences in the safety
      or immunologic profiles were noted for DTaP(5)-IPV-Hib versus the separately
      administered, US-licensed equivalent vaccines. DTaP(5)-IPV-Hib is a suitable
      replacement for separately administered DTaP, IPV, and Hib vaccines.

PMID- 19117898
TI  - Comparison of computer tomography and magnetic resonance imaging scans on the
      third day of life in term newborns with neonatal encephalopathy.
AB  - OBJECTIVE: Our goal was to compare the patterns of brain injury detected by
      computed tomography, conventional MRI (T1- and T2-weighted sequences), and
      diffusion-weighted MRI in a cohort of term newborns with neonatal encephalopathy
      studied uniformly with all 3 modalities on the third day of life. METHODS: Term
      newborns (> or =36 weeks' gestation) admitted to our center with neonatal
      encephalopathy were scanned with computed tomography, MRI, and diffusion-weighted
      MRI at 72 (+/-12) hours of life (n = 48). Each modality was scored independently
      of the other with previously validated scoring systems. The predominant pattern
      of brain injury was classified as: normal, watershed, basal nuclei, total
      (maximal basal nuclei and watershed), and focal-multifocal (presence of strokes
      and/or white matter injury alone). RESULTS: The agreement for the predominant
      pattern of injury was excellent between MRI and diffusion-weighted MRI (77%
      agreement). The agreement for the pattern of injury was also good for computed
      tomography and diffusion-weighted MRI (67% agreement). The extent of cortical
      injury and focal-multifocal lesions, such as strokes and white matter injury,
      were less apparent on computed tomography than diffusion-weighted MRI. In 19
      newborns with a repeat MRI in the second week of life, the predominant pattern
      seen on the day 3 diffusion-weighted MRI was confirmed. CONCLUSIONS: Diffusion
      weighted MRI is the most sensitive technique with which to assess brain injury on
      day 3 of life in term newborns with neonatal encephalopathy, particularly for
      cortical injury and focal-multifocal lesions such as stroke and white matter
      injury. All 3 modalities identify the most serious patterns of brain injury
      similarly.

PMID- 19117899
TI  - Hyperbilirubinemia and language delay in premature infants.
AB  - OBJECTIVE: Our goal was to evaluate whether language delay at 3 years in
      premature infants is associated with previous exposure to hyperbilirubinemia
      during the first 2 weeks after birth. PATIENTS AND METHODS: We performed a
      retrospective case-control study of infants admitted to the NICU between January
      and October 2003. Inclusion criteria included a birth weight of < or =1500 g and
      follow-up to age 3 years. Exclusion criteria included genetic disorders and
      hearing loss or recurrent ear infections. Peak total serum bilirubin levels
      during the first 2 weeks and duration of hyperbilirubinemia (days with total
      serum bilirubin level at >8 mg/dL) were determined. Infants with language delay
      and who were receiving speech therapy by 3 years were identified through
      developmental clinic charts and a tracking program and compared with infants who
      had normal language development. RESULTS: A total of 125 infants with birth
      weight of < or =1500 g were admitted to the NICU between January and October
      2003. Fifteen infants died, and 110 were discharged from the hospital. A total of
      102 (93%) of 110 infants had follow-up to the age of 3 years. Four infants were
      excluded (1 genetic disorder, 3 delayed hearing loss or recurrent ear
      infections). Twenty-four infants had a language delay and received speech
      therapy, whereas 74 infants had normal language development. There was no
      significant difference in peak total serum bilirubin level and duration of
      hyperbilirubinemia between the 2 groups. On logistic regression, only
      bronchopulmonary dysplasia was associated with language delay. CONCLUSIONS:
      Hyperbilirubinemia, defined as peak total serum bilirubin level or duration of
      elevated bilirubin in days, is not associated with language delay in premature
      infants. However, this issue deserves investigation, because other measures of
      bilirubin, such as unbound bilirubin, may be associated with language delay.

PMID- 19117900
TI  - A single-blinded, randomized comparison of laparoscopic versus open hernia repair
      in children.
AB  - OBJECTIVE: The role of laparoscopic surgery in pediatric inguinal hernia repair
      is unclear. We aimed to compare day-case laparoscopic hernia repair with open
      repair. METHODS: A prospective, single-blinded randomized study in children aged
      4 months to 16 years with unilateral inguinal hernia was performed. The primary
      outcome measure was the time to normal daily activities after surgery. Secondary
      outcome measures included postoperative pain, time in the operation room,
      results, and complications. RESULTS: Eighty-nine patients were enrolled
      (laparoscopic hernia repair: 47, open repair: 42). The mean number of days to
      normal activity after laparoscopic hernia repair and open repair was 2.4 and 2.5,
      respectively. Thirty-seven (79%) patients with laparoscopic hernia repair and 20
      (42%) with open repair required rescue analgesia postoperatively. The median pain
      score in the second postoperative morning was significantly higher after
      laparoscopic hernia repair. The median times in the operation room for
      laparoscopic hernia repair and open repair were 63 and 38 minutes, respectively.
      Surgical and cosmetic results were similar at up to 2 years' follow-up.
      CONCLUSIONS: Recovery and outcome were similar after open repair and laparoscopic
      hernia repair in children. Laparoscopic hernia repair was associated with
      increased theater time and postoperative pain.

PMID- 19117897
TI  - Using a count of neonatal morbidities to predict poor outcome in extremely low
      birth weight infants: added role of neonatal infection.
AB  - OBJECTIVE: A count of 3 neonatal morbidities (bronchopulmonary dysplasia, brain
      injury, and severe retinopathy of prematurity) strongly predict the risk of death
      or neurosensory impairment in extremely low birth weight infants who survive to
      36 weeks' postmenstrual age. Neonatal infection has also been linked with later
      impairment. We examined whether the addition of infection to the count of 3
      neonatal morbidities further improves the prediction of poor outcome. METHODS: We
      studied 944 infants who participated in the Trial of Indomethacin Prophylaxis in
      Preterms and survived to 36 weeks' postmenstrual age. Culture-proven sepsis,
      meningitis, and stage II or III necrotizing enterocolitis were recorded
      prospectively. We investigated the incremental prognostic importance of neonatal
      infection by adding terms for the different types of infection to a logistic
      model that already contained terms for the count of bronchopulmonary dysplasia,
      brain injury, and severe retinopathy. Poor outcome at 18 months of age was death
      or survival with 1 or more of the following: cerebral palsy, cognitive delay,
      severe hearing loss, and bilateral blindness. RESULTS: There were 414 (44%)
      infants with at least 1 episode of infection or necrotizing enterocolitis.
      Meningitis and the presence of any type of infection added independent prognostic
      information to the morbidity-count model. The odds ratio associated with
      infection or necrotizing enterocolitis in this model was 50% smaller than the
      odds ratio associated with each count of the other 3 neonatal morbidities.
      Meningitis was rare and occurred in 22 (2.3%) of 944 infants. CONCLUSIONS: In
      this cohort of extremely low birth weight infants who survived to 36 weeks'
      postmenstrual age, neonatal infection increased the risk of a late death or
      survival with neurosensory impairment. However, infection was a weaker predictor
      of poor outcome than bronchopulmonary dysplasia, brain injury, and severe
      retinopathy.

PMID- 19117901
TI  - Impact of fundoplication versus gastrojejunal feeding tubes on mortality and in
      preventing aspiration pneumonia in young children with neurologic impairment who
      have gastroesophageal reflux disease.
AB  - OBJECTIVE: Aspiration pneumonia is the most common cause of death in children
      with neurologic impairment who have gastroesophageal reflux disease.
      Fundoplications and gastrojejunal feeding tubes are frequently employed to
      prevent aspiration pneumonia in this population. Which of these approaches is
      more effective in preventing aspiration pneumonia and/or improving survival is
      unknown. The objective of this study was to compare outcomes for children with
      neurologic impairment and gastroesophageal reflux disease after either a first
      fundoplication or a first gastrojejunal feeding tube. PATIENTS AND METHODS: This
      was a retrospective, observational cohort study of children with neurologic
      impairment who had either a fundoplication or gastrojejunal feeding tube between
      January 1997 and December 2005 at a tertiary care children's hospital. Main
      outcome measures were postprocedure aspiration pneumonia-free survival and
      mortality. Propensity analyses were used to control for bias in treatment
      assignment and prognostic imbalances. RESULTS: Of the 366 children with
      neurologic impairment and gastroesophageal reflux disease, 43 had a first
      gastrojejunal feeding tube and 323 underwent a first fundoplication. Median
      length of follow-up was 3.4 years. Children who received a first fundoplication
      had similar rates of aspiration pneumonia and mortality after the procedure
      compared with those who had a first gastrojejunal feeding tube, when adjusting
      for the treatment assignment using propensity scores. CONCLUSIONS: Aspiration
      pneumonia and mortality are not uncommon events after either a first
      fundoplication or a first gastrojejunal feeding tube for the management of
      gastroesophageal reflux disease in children with neurologic impairment. Neither
      treatment option is clearly superior in preventing the subsequent aspiration
      pneumonia or improving overall survival for these children. This complex clinical
      scenario needs to be studied in a prospective, multicenter, randomized control
      trial to evaluate definitively whether 1 of these 2 management options is more
      beneficial.

PMID- 19117902
TI  - Family rejection as a predictor of negative health outcomes in white and Latino
      lesbian, gay, and bisexual young adults.
AB  - OBJECTIVE: We examined specific family rejecting reactions to sexual orientation
      and gender expression during adolescence as predictors of current health problems
      in a sample of lesbian, gay, and bisexual young adults. METHODS: On the basis of
      previously collected in-depth interviews, we developed quantitative scales to
      assess retrospectively in young adults the frequency of parental and caregiver
      reactions to a lesbian, gay, or bisexual sexual orientation during adolescence.
      Our survey instrument also included measures of 9 negative health indicators,
      including mental health, substance abuse, and sexual risk. The survey was
      administered to a sample of 224 white and Latino self-identified lesbian, gay,
      and bisexual young adults, aged 21 to 25, recruited through diverse venues and
      organizations. Participants completed self-report questionnaires by using either
      computer-assisted or pencil-and-paper surveys. RESULTS: Higher rates of family
      rejection were significantly associated with poorer health outcomes. On the basis
      of odds ratios, lesbian, gay, and bisexual young adults who reported higher
      levels of family rejection during adolescence were 8.4 times more likely to
      report having attempted suicide, 5.9 times more likely to report high levels of
      depression, 3.4 times more likely to use illegal drugs, and 3.4 times more likely
      to report having engaged in unprotected sexual intercourse compared with peers
      from families that reported no or low levels of family rejection. Latino men
      reported the highest number of negative family reactions to their sexual
      orientation in adolescence. CONCLUSIONS: This study establishes a clear link
      between specific parental and caregiver rejecting behaviors and negative health
      problems in young lesbian, gay, and bisexual adults. Providers who serve this
      population should assess and help educate families about the impact of rejecting
      behaviors. Counseling families, providing anticipatory guidance, and referring
      families for counseling and support can help make a critical difference in
      helping decrease risk and increasing well-being for lesbian, gay, and bisexual
      youth.

PMID- 19117903
TI  - Inhaled corticosteroids and asthma control in children: assessing impairment and
      risk.
AB  - OBJECTIVE: To review the use of inhaled corticosteroids on asthma control in
      children by using the new therapeutic paradigm outlined in the Expert Panel
      Report 3: Guidelines for the Diagnosis and Management of Asthma. METHODS: A
      systematic review of the literature was performed by using the Medline and Embase
      databases (January 1996 to October 2007). RESULTS: A total of 18 placebo
      controlled, clinical trials in >8000 children (aged 0-17 years) with asthma met
      the criteria for evaluating monotherapy with inhaled corticosteroids: 13 double
      blind studies of inhaled corticosteroids versus placebo and 5 controlled studies
      that compared inhaled corticosteroids to a nonsteroid antiinflammatory agent. The
      findings can be summarized as follows: (1) Compared with placebo, inhaled
      corticosteroid treatment was associated with reductions in both the impairment
      and risk domains. (2) Improvements in impairment and risk observed with inhaled
      corticosteroids were generally greater than those observed with nonsteroid
      antiinflammatory comparator medications. (3) Inhaled corticosteroids were well
      tolerated. (4) Small reductions in growth rates were evident when compared with
      placebo and/or comparator nonsteroid antiinflammatory medication use in the long
      term (>1-year) studies, but when measured, the reductions diminished with time.
      CONCLUSIONS: Treatment with inhaled corticosteroids improves the asthma-control
      domains of impairment and risk in children. Differences in study protocols make
      detailed comparisons difficult. Specific needs for additional trials include (1)
      more studies using appropriate indicators for impairment (eg, rescue-medication
      use; symptoms scores; asthma/episode-free days) and risk (eg, forced expiratory
      volume in 1 second in children who can perform spirometry; exacerbations
      requiring oral corticosteroids; urgent care usage) and (2) more studies
      evaluating adolescents; the majority of the data reported were for children up to
      the age of 12 years, and data for adolescents are often lost (either grouped with
      adults [eg, studies in patients > or =12 years old] or not included [eg, studies
      of school-aged children < or =12 years old]). Attention should be given to
      standardizing variables that will permit comparison of outcomes between trials.

PMID- 19117904
TI  - Finding the optimal postnatal dexamethasone regimen for preterm infants at risk
      of bronchopulmonary dysplasia: a systematic review of placebo-controlled trials.
AB  - CONTEXT: Postnatal dexamethasone therapy reduces the incidence of
      bronchopulmonary dysplasia in preterm infants but may be associated with an
      increased risk for adverse neurodevelopmental outcome. OBJECTIVE: Our goal was to
      determine if the effects of dexamethasone on mortality and pulmonary and
      neurodevelopmental sequelae in preterm infants are modified by the cumulative
      dose given. METHODS: Randomized, controlled trials comparing dexamethasone with
      placebo in ventilated preterm infants >7 days old were identified by searching
      the electronic databases and the abstracts from the Pediatric Academic societies
      and by performing manual reference searches. Two reviewers independently assessed
      eligibility and quality of trials and extracted data on study design, patient
      characteristics, and relevant outcomes. Original trialists were asked to provide
      additional data. RESULTS: Sixteen trials including 1136 patients were analyzed by
      using meta-analysis and metaregression. Additional data were provided by 12
      original trialists. Trials with a moderately early (7- to 14-day) or delayed (>3
      week) postnatal treatment onset were analyzed separately. Higher dexamethasone
      doses reduced the relative risk for the combined outcome, mortality or
      bronchopulmonary dysplasia, with the largest effect in trials that used a
      cumulative dose of >4 mg/kg. No effect was found of doses on the risk of
      neurodevelopmental sequelae in the delayed treatment studies, but in the
      moderately-early-treatment studies the risk of mortality or cerebral palsy
      decreased by 6.2%, and the risk of a Mental Developmental Index below -2 SDs
      decreased by 6.6% for each incremental mg/kg cumulative dexamethasone dose.
      CONCLUSIONS: Higher cumulative dexamethasone doses administered after the first
      week of life may decrease the risk for bronchopulmonary dysplasia without
      increasing the risk for neurodevelopmental sequelae in ventilated preterm
      infants. A large randomized trial is needed to confirm or refute these findings.

PMID- 19117906
TI  - Clinical and molecular study of 320 children with Marfan syndrome and related
      type I fibrillinopathies in a series of 1009 probands with pathogenic FBN1
      mutations.
AB  - From a large series of 1009 probands with pathogenic FBN1 mutations, data for 320
      patients <18 years of age at the last follow-up evaluation were analyzed (32%).
      At the time of diagnosis, the median age was 6.5 years. At the last examination,
      the population was classified as follows: neonatal Marfan syndrome, 14%; severe
      Marfan syndrome, 19%; classic Marfan syndrome, 32%; probable Marfan syndrome,
      35%. Seventy-one percent had ascending aortic dilation, 55% ectopia lentis, and
      28% major skeletal system involvement. Even when aortic complications existed in
      childhood, the rates of aortic surgery and aortic dissection remained low (5% and
      1%, respectively). Some diagnostic features (major skeletal system involvement,
      striae, dural ectasia, and family history) were more frequent in the 10- to <18
      year age group, whereas others (ascending aortic dilation and mitral
      abnormalities) were more frequent in the population with neonatal Marfan
      syndrome. Only 56% of children could be classified as having Marfan syndrome,
      according to international criteria, at their last follow-up evaluation when the
      presence of a FBN1 mutation was not considered as a major feature, with
      increasing frequency in the older age groups. Eighty-five percent of child
      probands fulfilled international criteria after molecular studies, which
      indicates that the discovery of a FBN1 mutation can be a valuable diagnostic aid
      in uncertain cases. The distributions of mutation types and locations in this
      pediatric series revealed large proportions of probands carrying mutations
      located in exons 24 to 32 (33%) and in-frame mutations (75%). Apart from lethal
      neonatal Marfan syndrome, we confirm that the majority of clinical manifestations
      of Marfan syndrome increase with age, which emphasizes the poor applicability of
      the international criteria to this diagnosis in childhood and the need for follow
      up monitoring in cases of clinical suspicion of Marfan syndrome.

PMID- 19117905
TI  - Advances in the treatment of fragile X syndrome.
AB  - The FMR1 mutations can cause a variety of disabilities, including cognitive
      deficits, attention-deficit/hyperactivity disorder, autism, and other
      socioemotional problems, in individuals with the full mutation form (fragile X
      syndrome) and distinct difficulties, including primary ovarian insufficiency,
      neuropathy and the fragile X-associated tremor/ataxia syndrome, in some older
      premutation carriers. Therefore, multigenerational family involvement is commonly
      encountered when a proband is identified with a FMR1 mutation. Studies of
      metabotropic glutamate receptor 5 pathway antagonists in animal models of fragile
      X syndrome have demonstrated benefits in reducing seizures, improving behavior,
      and enhancing cognition. Trials of metabotropic glutamate receptor 5 antagonists
      are beginning with individuals with fragile X syndrome. Targeted treatments,
      medical and behavioral interventions, genetic counseling, and family supports are
      reviewed here.

PMID- 19117908
TI  - Models of comprehensive multidisciplinary care for individuals in the United
      States with genetic disorders.
AB  - Approaches to providing comprehensive coordinated care for individuals with
      complex diseases include the medical home approach, the chronic care model in
      primary care, and disease-specific, multidisciplinary specialty clinics. There is
      uneven availability and utilization of multidisciplinary specialty clinics for
      different genetic diseases. For 2 disorders (ie, hemophilia and cystic fibrosis),
      effective national networks of specialty clinics exist and reach large
      proportions of the target populations. For other disorders, notably, sickle cell
      disease, fewer such centers are available, centers are less likely to be
      networked, and centers are used less widely. Models of comanagement are essential
      for promoting ongoing communication and coordination between primary care and
      subspecialty services, particularly during the transition from pediatric care to
      adult care. Evaluation of the effectiveness of different models in improving
      outcomes for individuals with genetic diseases is essential.

PMID- 19117907
TI  - Childhood obesity and medical neglect.
AB  - The incidence of childhood obesity has increased dramatically, including severe
      childhood obesity and obesity-related comorbid conditions. Cases of severe
      childhood obesity have prompted the following question: does childhood obesity
      ever constitute medical neglect? In our opinion, removal of a child from the home
      is justified when all 3 of the following conditions are present: (1) a high
      likelihood that serious imminent harm will occur; (2) a reasonable likelihood
      that coercive state intervention will result in effective treatment; and (3) the
      absence of alternative options for addressing the problem. It is not the mere
      presence or degree of obesity but rather the presence of comorbid conditions that
      is critical for the determination of serious imminent harm. All 3 criteria are
      met in very limited cases, that is, the subset of obese children who have serious
      comorbid conditions and for whom all alternative options have been exhausted. In
      these limited cases, a trial of enforced treatment outside the home may be
      indicated, to protect the child from irreversible harm.

PMID- 19117909
TI  - The rebirth of pediatrics.

PMID- 19117910
TI  - Complementary roles for amygdala and periaqueductal gray in temporal-difference
      fear learning.
AB  - Pavlovian fear conditioning is not a unitary process. At the neurobiological
      level multiple brain regions and neurotransmitters contribute to fear learning.
      At the behavioral level many variables contribute to fear learning including the
      physical salience of the events being learned about, the direction and magnitude
      of predictive error, and the rate at which these are learned about. These
      experiments used a serial compound conditioning design to determine the roles of
      basolateral amygdala (BLA) NMDA receptors and ventrolateral midbrain
      periaqueductal gray (vlPAG) mu-opioid receptors (MOR) in predictive fear
      learning. Rats received a three-stage design, which arranged for both positive
      and negative prediction errors producing bidirectional changes in fear learning
      within the same subjects during the test stage. Intra-BLA infusion of the NR2B
      receptor antagonist Ifenprodil prevented all learning. In contrast, intra-vlPAG
      infusion of the MOR antagonist CTAP enhanced learning in response to positive
      predictive error but impaired learning in response to negative predictive error-
      a pattern similar to Hebbian learning and an indication that fear learning had
      been divorced from predictive error. These findings identify complementary but
      dissociable roles for amygdala NMDA receptors and vlPAG MOR in temporal
      difference predictive fear learning.

PMID- 19117911
TI  - Critical role of the cholinergic system for object-in-place associative
      recognition memory.
AB  - Object-in-place memory, which relies on the formation of associations between an
      object and the place in which it was encountered, depends upon a neural circuit
      comprising the perirhinal (PRH) and medial prefrontal (mPFC) cortices. This study
      examined the contribution of muscarinic cholinergic neurotransmission within this
      circuit to such object-in-place associative memory. Intracerebral administration
      of scopolamine in the PRH or mPFC impaired memory acquisition, but not retrieval
      and importantly we showed that unilateral blockade of muscarinic receptors
      simultaneously in both regions in opposite hemispheres, significantly impaired
      performance. Thus, object-in-place associative memory depends upon cholinergic
      modulation of neurones within the PRH-PFC circuit.

PMID- 19117912
TI  - Social modulation of associative fear learning by pheromone communication.
AB  - Mice communicate through visual, vocal, and olfactory cues that influence innate,
      nonassociative behavior. We here report that exposure to a recently fear
      conditioned familiar mouse impairs acquisition of conditioned fear and
      facilitates fear extinction, effects mimicked by both an olfactory chemosignal
      emitted by a recently fear-conditioned familiar mouse and by the putative stress
      related anxiogenic pheromone beta-phenylethylamine (beta-PEA). Together, these
      findings suggest social modulation of higher-order cognitive processing through
      pheromone communication and support the concurrent excitor hypothesis of
      extinction learning.

PMID- 19117913
TI  - Circadian modulation of short-term memory in Drosophila.
AB  - Endogenous biological clocks are widespread regulators of behavior and
      physiology, allowing for a more efficient allocation of efforts and resources
      over the course of a day. The extent that different processes are regulated by
      circadian oscillators, however, is not fully understood. We investigated the role
      of the circadian clock on short-term associative memory formation using a
      negatively reinforced olfactory-learning paradigm in Drosophila melanogaster. We
      found that memory formation was regulated in a circadian manner. The peak
      performance in short-term memory (STM) occurred during the early subjective night
      with a twofold performance amplitude after a single pairing of conditioned and
      unconditioned stimuli. This rhythm in memory is eliminated in both timeless and
      period mutants and is absent during constant light conditions. Circadian gating
      of sensory perception does not appear to underlie the rhythm in short-term memory
      as evidenced by the nonrhythmic shock avoidance and olfactory avoidance
      behaviors. Moreover, central brain oscillators appear to be responsible for the
      modulation as cryptochrome mutants, in which the antennal circadian oscillators
      are nonfunctional, demonstrate robust circadian rhythms in short-term memory.
      Together these data suggest that central, rather than peripheral, circadian
      oscillators modulate the formation of short-term associative memory and not the
      perception of the stimuli.

PMID- 19117914
TI  - Genetic inactivation of D-amino acid oxidase enhances extinction and reversal
      learning in mice.
AB  - Activation of the N-methyl-D-aspartate receptor (NMDAR) glycine site has been
      shown to accelerate adaptive forms of learning that may benefit psychopathologies
      involving cognitive and perseverative disturbances. In this study, the effects of
      increasing the brain levels of the endogenous NMDAR glycine site agonist D
      serine, through the genetic inactivation of its catabolic enzyme D-amino acid
      oxidase (DAO), were examined in behavioral tests of learning and memory. In the
      Morris water maze task (MWM), mice carrying the hypofunctional Dao1(G181R)
      mutation demonstrated normal acquisition of a single platform location but had
      substantially improved memory for a new target location in the subsequent
      reversal phase. Furthermore, Dao1(G181R) mutant animals exhibited an increased
      rate of extinction in the MWM that was similarly observed following
      pharmacological administration of D-serine (600 mg/kg) in wild-type C57BL/6J
      mice. In contextual and cued fear conditioning, no alterations were found in
      initial associative memory recall; however, extinction of the contextual fear
      memory was facilitated in mutant animals. Thus, an augmented level of D-serine
      resulting from reduced DAO activity promotes adaptive learning in response to
      changing conditions. The NMDAR glycine site and DAO may be promising therapeutic
      targets to improve cognitive flexibility and inhibitory learning in psychiatric
      disorders such as schizophrenia and anxiety syndromes.

PMID- 19117916
TI  - Role of dopamine receptors subtypes, D1-like and D2-like, within the nucleus
      accumbens subregions, core and shell, on memory consolidation in the one-trial
      inhibitory avoidance task.
AB  - Recent evidence demonstrated that dopamine within the nucleus accumbens mediates
      consolidation of both associative and nonassociative memories. However, the
      specific contribution of the nucleus accumbens subregions, core and shell, and of
      D1 and D2 receptors subtypes has not been yet clarified. The aim of this study
      was, therefore, to directly compare the effect of D1 and D2 dopamine receptor
      blockade within the core and the shell subregions of the nucleus accumbens on
      memory consolidation. Using the one-trial inhibitory avoidance task in CD1 mice,
      we demonstrated that SCH 23390 (vehicle, 12.5, 25, 50 ng/side) administration
      within the core, but not the shell, impaired step-through latency 24 h after the
      administration if injected immediately, but not 120 min post-training.
      Interestingly, sulpiride (vehicle, 25, 50 ng/side) injection in both the core and
      the shell of the accumbens affected step-through latency 24 h later; also, in
      this case the impairment was time dependent. These data provide the most complete
      and direct demonstration to date that early consolidation of aversive memory
      requires D2 receptor activation in both nucleus accumbens subregions, and D1
      activation selectively in the nucleus accumbens core.

PMID- 19117915
TI  - Hippocampal and extrahippocampal systems compete for control of contextual fear:
      role of ventral subiculum and amygdala.
AB  - Two neural systems, a hippocampal system and an extrahippocampal system compete
      for control over contextual fear, and the hippocampal system normally dominates.
      Our experiments reveal that output provided by the ventral subiculum is critical
      for the hippocampal system to win this competition. Bilateral electrolytic
      lesions of the ventral subiculum after conditioning, but not before conditioning,
      impaired contextual fear conditioning. Reversibly inactivating this region by
      bilateral injections of muscimol produced the same results-no impairment when the
      injection occurred prior to conditioning but a significant impairment when this
      region was inactivated after conditioning. Thus, the extrahippocampal system can
      support contextual fear conditioning if the ventral subiculum is disabled before
      conditioning but not if it is disabled after conditioning. Our experiments also
      reveal that the basolateral region of the amygdala (BLA) is where the two systems
      compete for associative control of the fear system. To test this hypothesis we
      reasoned that the extrahippocampal system would also acquire associative control
      over the fear system, even if the hippocampal system were functional, if the
      basal level of plasticity potential in the BLA could be increased. We did this by
      injecting the D1 dopamine agonist, SKF82958, into the BLA just prior to
      conditioning. This treatment resulted in a significant increase in freezing when
      the ventral subiculum was disabled prior to the test. These results are discussed
      in relationship to the idea that D1 agonists increase plasticity potential by
      increasing the pool of available extrasynaptic GluR1 receptors in the population
      of neurons supporting acquired fear.

PMID- 19117917
TI  - Prevalence of blindness and visual impairment in Nigeria: the National Blindness
      and Visual Impairment Study.
AB  - PURPOSE: To determine the prevalence of blindness and visual impairment among
      adults aged > or = 40 years in Nigeria. METHODS: Multistage, stratified, cluster
      random sampling with probability proportional to size procedures was used to
      identify a cross-sectional nationally representative sample of 15,027 persons >
      or = 40 years of age from all 36 states in Nigeria and the Federal Capital
      Territory. Distance visual acuity (VA) was measured with a reduced logMAR
      tumbling-E chart at 4 and 1 m. Presenting and best corrected visual acuities were
      recorded. Autorefraction was performed in all examined adults. Clinical
      evaluations included examination under dilation for those with presenting vision
      < 6/12 in either eye. RESULTS: In the study, 15,122 persons aged > or = 40 years
      were enumerated and 13,599 (89.9%) examined. Prevalence of blindness (< 20/400 in
      the better eye) and severe visual impairment (< 20/200-20/400; presenting vision)
      was 4.2% (95% confidence interval [CI]: 3.8%-4.6%) and 1.5% (95% CI: 1.3%-1.7%),
      respectively. Blindness was associated with increasing age, being female, poor
      literacy, and residence in the North. Participants residing in the South West had
      the lowest prevalence while those in the North East had the highest prevalence of
      blindness. It is estimated that 4.25 million adults aged > or = 40 years have
      moderate to severe visual impairment or blindness (< 20/63 in the better eye).
      CONCLUSIONS: There is a high prevalence of blindness and severe visual impairment
      among those aged > or = 40 years in Nigeria. Significant differences exist
      between the geopolitical zones and emphasis should be on ensuring eye services
      across Nigeria, which means that planning at the regional level is necessary.

PMID- 19117918
TI  - Life history of cones in the rhodopsin-mutant P23H-3 rat: evidence of long-term
      survival.
AB  - PURPOSE: To follow the status of cones over the life of the P23H-3 transgenic
      rat, while the rod population is depleted. METHODS: P23H-3 heterozygous and
      Sprague-Dawley (SD) control rats were raised in dim, cyclic light from postnatal
      day (P)10 to P540. Retinas were examined for cone density, cone outer segment
      (OS) length, cone axon and soma morphology, and the amplitude of rod and cone
      components of the electroretinogram (ERG) were determined. RESULTS: In the P23H-3
      retina, cone density followed a developmental pattern, increasing from P10 until
      P20, declining during early adult life (to P150), then steadying at levels found
      in the SD retina until P540. Cone OSs elongated to P30 and then slowly shortened
      during late adulthood; at P350 and P540, cone OSs were significantly shorter than
      in the background SD strain. Cone axons shortened slowly throughout adult life as
      the outer nuclear layer thinned. The rod a-wave declined steadily in the P23H-3
      retina from P10, falling below amplitudes seen in the SD strain from early life.
      By contrast, the cone b-wave maintained amplitude at SD levels, until P380.
      CONCLUSIONS: Despite the ongoing loss of rod function and numbers, cone numbers
      in the P23H-3 retina were maintained at levels found in the SD rat to the oldest
      age examined, and cone function and OS morphology were maintained for
      approximately 1 year, indicating a long period of cone independence. The long
      period of cone survival creates an opportunity to induce self-repair, if the
      stress causing their dysfunction can be reduced.

PMID- 19117919
TI  - Autologous transplantation of retinal pigment epithelium-Bruch's membrane complex
      for hemorrhagic age-related macular degeneration.
AB  - PURPOSE: To evaluate a surgical procedure for patients with hemorrhagic age
      related macular degeneration (AMD). METHODS: This procedure consisted of excision
      of the choroidal neovascular membrane and transplantation of autologous retinal
      pigment epithelium (RPE)-Bruch's membrane complex. The RPE-Bruch's membrane
      complex for transplantation was surgically developed by dissecting Bruch's
      membrane with the choriocapillaris from the medium size choroidal vessel layer at
      the midperipheral region of the choroid. Twenty-one eyes of 21 patients had this
      surgical procedure. Visual function tests included best corrected visual acuity
      (BCVA), multifocal (mf)ERG, and microperimetry. Optical coherence tomography
      (OCT), fluorescein angiography, and autofluorescence examinations were performed
      to study the status of the transplanted graft. RESULTS: Among the 21 eyes, 17
      with complete clinical data and qualified follow-up durations, which were 20.35
      +/- 10.31 months on average, were analyzed in this series. On the last follow-up
      visit, the mean for the ETDRS scores increased from 28.65 +/- 23.99 before
      surgery to 47.76 +/- 17.22 after surgery. Microperimetry showed that after
      surgery, seven eyes gained central fixation at the 12-month follow-up
      examination. However, two eyes lost their central fixation on the last follow-up
      visit. Fourteen (82.35%) of the transplanted patches preserved normal color
      without depigmentation. Among the 21 eyes, proliferative vitreoretinopathy (PVR)
      occurred in 3 (14.29%), and a recurrent neovascular membrane was observed in one
      eye (4.76%). CONCLUSIONS: The transplantation of the autologous RPE-Bruch's
      membrane complex can increase the visual acuity of patients with hemorrhagic AMD.
      The surviving transplanted graft with functional overlying retina was observed
      after surgery.

PMID- 19117920
TI  - Single choroideremia gene in nonmammalian vertebrates explains early embryonic
      lethality of the zebrafish model of choroideremia.
AB  - PURPOSE: Mutations of the CHM gene underlie the X-linked chorioretinal
      degeneration choroideremia (CHM). The affected gene product, Rab Escort Protein
      (REP)1, mediates the posttranslational prenyl modification of Rab GTPases. In
      patients with CHM, the related REP2 partially compensates for the loss of
      function of REP1. The objective of this investigation was to study the natural
      history of disease in a zebrafish model of CHM. METHODS: Zebrafish chm(-/-) were
      bred and subjected to extensive histologic analysis and TUNEL assays, and
      cellular extracts were used for immunoblot and in vitro prenylation assays. A
      detailed evolutionary analysis was performed on the REP family. RESULTS: The
      retina of chm(-/-) zebrafish develops normally for the first 4 days
      postfertilization (dpf) but that catastrophic multilayer degeneration synchronous
      with severe multisystem disease follows. Mean survival time is 4.8 dpf. At the
      onset of generalized disease, a significant reduction in rep expression levels
      and activity, with unprenylated rabs accumulating in the cytosol was
      demonstrated. Extensive bioinformatic analysis of the REP family of proteins
      revealed a single rep isoform in fish and other nonmammalian vertebrates and
      invertebrates that is similar to mammalian REP1. CONCLUSIONS: REP1 appears to be
      the ancestral gene in the family, whereas the intronless REP2 gene is restricted
      to the mammalian lineage. The results of this study propose that in chm(-/-)
      zebrafish, maternally derived rep allows initial successful development of the
      embryo, but its gradual loss leads to multisystem disease and invariably to
      lethality. In its current form, the chm(-/-) zebrafish has limited usefulness.

PMID- 19117921
TI  - Fibrocontractive Muller cell phenotypes in proliferative diabetic retinopathy.
AB  - PURPOSE: To evaluate Muller cells as a potential source of fibrocontractive cells
      in proliferative diabetic retinopathy. METHODS: Temporal changes in glial
      fibrillary acidic protein (GFAP), vimentin, glutamine synthetase, and alpha
      smooth muscle actin (alphaSMA) expression in cultures of freshly isolated porcine
      Muller cells were evaluated by indirect immunofluorescence and Western blotting.
      A similar evaluation was performed on freshly isolated Muller cells maintained in
      high- and low-glucose culture. Cryosections of six diabetic epiretinal tissues
      were evaluated for the same antigens. RESULTS: Muller cell changes in culture
      included loss of glutamine synthetase and GFAP, with coincident gains in alphaSMA
      immunoreactivity. Vimentin immunoreactivity persisted without obvious change.
      Similar changes were observed when the cells were maintained in high- or low
      glucose culture medium. All six diabetic epiretinal membranes contained
      positively identified Muller cells with vimentin, GFAP, and glutamine synthetase
      immunoreactivities. There was a progressive loss of glutamine synthetase and GFAP
      content and a coincident increase in alphaSMA content as the cells assumed an
      elongated, fibroblastlike morphology. CONCLUSIONS: Continuous culture in high-
      versus low-glucose medium does not influence Muller cell phenotype changes.
      Positively identified Muller cells are present in diabetic epiretinal tissues and
      appear to undergo the same progression of phenotype changes observed in culture.
      Cells capable of generating tractional forces associated with proliferative
      diabetic retinopathy can arise from Muller cells.

PMID- 19117922
TI  - Defining the residual vision in leber congenital amaurosis caused by RPE65
      mutations.
AB  - PURPOSE: To quantify the residual vision in Leber congenital amaurosis (LCA)
      caused by RPE65 mutations. METHODS: Patients with RPE65-LCA (n = 30; ages, 4-55)
      were studied using electroretinography (ERG), full-field stimulus testing (FST),
      kinetic and static threshold perimetry, and optical coherence tomography (OCT).
      RESULTS: All patients with RPE65-LCA had abnormal ERGs even at the youngest ages.
      There were no detectable rod ERGs and only reduced cone ERGs. By chromatic FST,
      however, 59% of patients had measurable rod- and cone-mediated function. The
      remaining 41% had only cone-mediated function. Extent of kinetic fields varied
      widely in the first two decades of life but, by the end of the third decade,
      there was very little measurable field. Regional patterns of visual loss were
      evident using dark-adapted static threshold perimetry. The mildest dysfunctions
      showed relatively homogeneous sensitivity loss beyond the central field. Mid
      peripheral dysfunction was a later feature; finally, only central and peripheral
      islands remained. Colocalized measures of visual function and retinal structure
      by OCT showed that visual function was detectable when a photoreceptor layer was
      detectable. CONCLUSIONS: Residual rod as well as cone function is detectable in
      RPE65-LCA. The finding of different regional patterns of visual loss in these
      patients suggests that the optimal retinal site(s) for subretinal gene delivery
      to achieve efficacy are likely to change with disease progression.

PMID- 19117923
TI  - Oxygen saturation in human retinal vessels is higher in dark than in light.
AB  - PURPOSE: Animal studies have indicated that retinal oxygen consumption is greater
      in dark than light. In this study, oxygen saturation is measured in retinal
      vessels of healthy humans during dark and light. METHODS: The oximeter consists
      of a fundus camera, a beam splitter, a digital camera and software, which
      calculates hemoglobin oxygen saturation in the retinal vessels. In the first
      experiment, 18 healthy individuals underwent oximetry measurements after 30
      minutes in the dark, followed by alternating 5-minute periods of white light (80
      cd/m(2)) and dark. In the second experiment, 23 volunteers underwent oximetry
      measurements after 30 minutes in the dark, followed by light at 1, 10, and 100
      cd/m(2). Three subjects were excluded from analysis in the first experiment and
      four in the second experiment because of poor image quality. RESULTS: In the
      first experiment, the arteriolar saturation decreased from 92% +/- 4% (n = 15;
      mean +/- SD) after 30 minutes in the dark to 89% +/- 5% after 5 minutes in the
      light (P = 0.008). Corresponding numbers for venules are 60% +/- 5% in the dark
      and 55% +/- 10% (P = 0.020) in the light. In the second experiment, the
      arteriolar saturation was 92% +/- 4% in the dark and 88% +/- 7% in 100 cd/m(2)
      light (n = 19, P = 0.012). The corresponding values for venules were 59% +/- 9%
      in the dark and 55% +/- 10% in 100 cd/m(2) light (P = 0.065). CONCLUSIONS: Oxygen
      saturation in retinal blood vessels is higher in dark than in 80 or 100 cd/m(2)
      light in human retinal arterioles and venules. The authors propose that this is a
      consequence of increased oxygen demand in the outer retina in the dark.

PMID- 19117924
TI  - The circadian curve of intraocular pressure: can we estimate its characteristics
      during office hours?
AB  - PURPOSE: To verify whether office-hour measurements in patients in different body
      positions can estimate the characteristics of 24-hour intraocular pressure (IOP).
      METHODS: The 24-hour IOP curves of 29 healthy subjects (10 young adults, 19
      elderly) and 30 patients with untreated glaucoma were analyzed. Measurements were
      taken at 9 AM; 12, 3, 6, and 9 PM; and 12, 3, and 6 AM, both in the supine and
      sitting (Goldmann tonometer) positions. Peak, mean, and fluctuation of 24-hour
      IOP curves were compared with office-hour measurements obtained in subjects in
      the sitting position alone and with combined pressures obtained in the sitting
      and supine positions (four measurements in each body position from 9 AM to 6 PM).
      The percentage of subjects with estimates of all IOP parameters within a cutoff
      of +/-1 (peak and mean) and +/-2 mm Hg (fluctuation) was calculated. RESULTS:
      Office-hour sitting measurements correctly identified peak, mean, and IOP
      fluctuation in 10% of the young adults, 32% of the elderly control subjects, and
      20% of the patients with glaucoma, whereas the combination of supine and sitting
      measurements correctly identified them in 30%, 85%, and 46% of cases,
      respectively. It is noteworthy that office-hour measurements did not characterize
      any 24-hour parameter in 20% of patients with glaucoma. CONCLUSIONS: Compared
      with sitting measurements alone, the collection of supine and sitting office-hour
      measurements may enhance the correct identification of 24-hour IOP
      characteristics in both control subjects and untreated patients with glaucoma,
      thus reducing the need for obtaining 24-hour curves to a minority of patients.

PMID- 19117925
TI  - Effects of prostanoid EP agonists on mouse intraocular pressure.
AB  - PURPOSE: To investigate the ocular hypotensive effect and change of outflow
      facilities by prostaglandin E2 (PGE2) and selective agonists of PGE2 receptor
      subtypes (EP1, -2, -3, -4) using C57BL/6 (wild-type [WT]) mice or FP, EP1, -2,
      and -3 receptor-deficient mice. METHODS: IOP was measured with a microneedle, and
      IOP reduction was evaluated by the difference in IOP between the treated eye and
      the contralateral control eye. The time course and dose dependency of IOP
      reduction with PGE2 and the four selective EP receptor agonists were assessed.
      Aqueous humor outflow facility was measured by a two-level constant-pressure
      perfusion METHOD:  RESULTS: PGE2, ONO-AE1-259-01 (EP2 agonist), and ONO-AE1-329
      (EP4 agonist) significantly reduced IOP in a dose-dependent manner, whereas ONO
      DI-004 (EP1 agonist) and ONO-AE-248 (EP3 agonist) had no effect. Peak IOP
      reduction at 2 hours with 0.1% ONO-AE1-259-01 (EP2 agonist) and ONO-AE1-329 (EP4
      agonist) were 21.1% +/- 4.8% and 17.5% +/- 2.9%, respectively (P < 0.01). IOP
      reduction with ONO-AE1-259-01 (EP2 agonist) was completely eliminated in EP2
      knockout mice, but IOP reduction in other knockout mice was similar to that
      observed in WT mice. The effects of ONO-AE1-259-01 (EP2 agonist) and ONO-AE1-329
      (EP4 agonist) on the outflow facility were similar to those of their carrier.
      CONCLUSIONS: EP2 and EP4 receptors mediated IOP reduction in mice, whereas the
      contribution of EP1 and EP3 receptors was insignificant. The EP2 and EP4 receptor
      mediated mechanisms of IOP reduction were different from those mediated by the FP
      receptor.

PMID- 19117926
TI  - Upregulation of connexin43 expression in corneal fibroblasts by corneal
      epithelial cells.
AB  - PURPOSE: The authors have previously shown that the expression of tight-junction
      proteins in corneal epithelial cells is regulated by corneal fibroblasts in a
      coculture system. They have now examined the effect of corneal epithelial cells
      on the expression of the gap-junction protein connexin43 in corneal fibroblasts.
      METHODS: Human corneal fibroblasts and simian virus 40-transformed human corneal
      epithelial (HCE) cells were cultured on opposite sides of a collagen vitrigel
      membrane. Expression of junctional proteins in corneal fibroblasts was examined
      by reverse transcription-polymerase chain reaction, immunoblot, and
      immunofluorescence analyses. The effect of a small interfering RNA specific for
      insulin-like growth factor-1 (IGF-1) mRNA on connexin43 expression was determined
      by transfection. RESULTS: The amounts of connexin43 mRNA and protein in corneal
      fibroblasts were increased by the presence of HCE cells. HCE cells had no effect
      on the expression of the tight-junction proteins ZO-1, occludin, and claudin in
      corneal fibroblasts. The effect of HCE cells on connexin43 expression was
      mimicked by exposure of corneal fibroblasts to IGF-1. Furthermore, depletion of
      IGF-1 in HCE cells by RNA interference largely abolished the effect of these
      cells on connexin43 expression in corneal fibroblasts. Finally, the upregulation
      of connexin43 expression in corneal fibroblasts by HCE cells was blocked by
      inhibitors of signaling by the mitogen-activated protein kinases ERK (PD98059)
      and p38 MAPK (SB203580). CONCLUSIONS: The presence of corneal epithelial cells
      upregulated the expression of connexin43 in corneal fibroblasts, suggesting that
      corneal epithelial cells are important for the maintenance of gap junction
      mediated communication among corneal fibroblasts.

PMID- 19117927
TI  - Poly-epsilon-caprolactone intravitreous devices: an in vivo study.
AB  - PURPOSE: The objective of this study was to evaluate the long-term safety and
      pharmacokinetic profile of a dexamethasone-loaded poly-epsilon-caprolactone (PCL)
      intravitreous implant. METHODS: The PCL devices were prepared by compression and
      were inserted into the vitreous of pigmented rabbits. At different time points,
      vitreous samples were retrieved, and dexamethasone concentration was analyzed by
      high-performance liquid chromatography. The biodegradation of the implants was
      evaluated by scanning electron microscopy, and the dexamethasone remaining was
      evaluated at the end of follow-up. Clinical and histologic examinations were
      performed to evaluate the implant's tolerance. RESULTS: The PCL implant allows
      for a controlled and prolonged delivery of dexamethasone in rabbits eyes since it
      released the drug within the therapeutic range for at least 55 weeks. At 55 weeks
      approximately 79% of the drug was still present in the implant. Biodegradation
      study showed that PCL implants degradation is very slow. Clinical and histologic
      observations showed that the devices were very well tolerated in the rabbit eye.
      CONCLUSIONS: This study demonstrates the feasibility and tolerance of
      intravitreous PCL drug delivery systems, which can offer a wide range of
      applications for intraocular drug delivery because of their controlled and
      prolonged release over months or even years.

PMID- 19117928
TI  - Otago Glaucoma Surgery Outcome Study: the pattern of expression of MMPs and TIMPs
      in bleb capsules surrounding Molteno implants.
AB  - PURPOSE: To determine whether MMPs and TIMPs are present in the bleb wall of
      Molteno implants. METHODS: An observational case series consisting of ocular
      specimens from 10 human eyes obtained postmortem from patients who had undergone
      placement of Molteno implants for glaucoma. Immunohistochemistry was performed on
      the specimens to determine the distribution of MMP1, -2, and -3 and TIMP1, -2,
      and -3 in each bleb. The immunohistochemical staining was correlated with the
      histologic features observed in hematoxylin and eosin (H&E)-stained sections of
      the bleb wall. RESULTS: The specimens demonstrated extensive cytoplasmic staining
      for MMP1, -2, and -3 in fibroblasts within the bleb wall and in degenerating
      collagen near inner bleb wall fibroblasts undergoing apoptosis. In addition,
      there was staining for the presence of TIMP2 but not -1 or -3. CONCLUSIONS: MMPs
      are present in the bleb walls of Molteno implants. TIMP2 is expressed in most
      bleb capsules. The observations from this study support the hypothesis that bleb
      capsules undergo a cycle of collagen breakdown and renewal throughout the life of
      the bleb as members of the MMP family were localized in the bleb wall.

PMID- 19117929
TI  - The flavonoid, eriodictyol, induces long-term protection in ARPE-19 cells through
      its effects on Nrf2 activation and phase 2 gene expression.
AB  - PURPOSE: Eriodictyol, a flavonoid found in citrus fruits, is among the most
      potent compounds reported to protect human RPE cells from oxidative stress
      induced cell death. The present study sought to determine whether eriodictyol
      induced phase 2 protein expression further enhances the resistance of human ARPE
      19 cells to oxidative stress. METHODS: The ability of eriodictyol to activate
      Nrf2 and to induce the phase 2 proteins heme-oxygenase (HO)-1 and NAD(P)H:quinone
      oxidoreductase (NQO)-1, and the cellular antioxidant glutathione (GSH) were
      analyzed. Cytoprotection assays in ARPE-19 cells that were overexpressing HO-1 or
      NQO-1 were performed, cell survival after short-term and long-term eriodictyol
      treatment was compared, and the mechanism of protection using a dominant negative
      Nrf2 and shRNA specific for HO-1 was tested. RESULTS: Eriodictyol induced the
      nuclear translocation of Nrf2, enhanced the expression of HO-1 and NQO-1, and
      increased the levels of intracellular glutathione. ARPE-19 cells that overexpress
      HO-1 or NQO-1 were more resistant to oxidative stress-induced cell death than
      control cells. Eriodictyol induced long-term protection significantly greater
      than its short-term protection. This effect was correlated temporally with the
      activation of Nrf2 and the induction of phase 2 enzymes and could be blocked with
      the use of a dominant negative Nrf2 and shRNA specific to HO-1. CONCLUSIONS:
      These findings indicate that the greatest benefit from eriodictyol may be its
      ability to regulate gene expression and enhance multiple cellular defenses to
      oxidative injury.

PMID- 19117930
TI  - Vision- and health-related quality of life in patients with visual field loss
      after postchiasmatic lesions.
AB  - PURPOSE: The purpose of the study was to assess vision-related quality of life
      (QoL) in patients with visual field loss (VFL) after lesions of the
      postchiasmatic visual pathway and to investigate the influence of VFL and reduced
      visual acuity (VA) on vision-related QoL. METHODS: In 312 patients with
      postchiasmatic damage, VFL was measured by automated computer campimetry, and
      vision-related QoL was assessed by the National Eye Institute Visual Functioning
      Questionnaire (NEI-VFQ). Health-related QoL was obtained by the SF-36 Health
      Survey in 272 patients. In addition, 90 degrees visual fields and VA data were
      obtained. NEI-VFQ and SF-36 scores were compared with those of healthy subjects
      and poststroke, brain-injured patients in general. Multiple analyses of
      covariance and multiple linear regression models for QoL results were performed
      with VA and VFL as independent variables. RESULTS: Patients with postchiasmatic
      lesions who had VFL had markedly lower NEI-VFQ scores than did healthy subjects
      and also lower SF-36 scores than did poststroke, brain-injured patients,
      particularly in the domain of role functioning. VFL and VA correlated
      significantly with vision-related but not with health-related QoL estimates when
      age was considered as confounding variable. Most scales of NEI-VFQ (9/12) were
      sensitive to differences in VFL. CONCLUSIONS: VFL and VA had a coordinate
      influence on vision-related QoL in brain-injured patients with postchiasmatic
      lesions. Diminished health-related QoL was not associated with VFL and VA. Both
      VFL and VA should be considered when trying to explain variance of NEI-VFQ
      results in patients with postchiasmatic lesions of the visual pathway.

PMID- 19117931
TI  - Relationship among oxidative stress, DNA damage, and proliferative capacity in
      human corneal endothelium.
AB  - PURPOSE: To determine whether human corneal endothelial cells (HCECs) exhibit
      signs of oxidative DNA damage and to test whether oxidative stress affects the
      proliferative capacity of HCECs. METHODS: Donor human corneas were divided into
      two age groups: young (<30 years) and older (>50 years). An 8-hydroxy-2'
      deoxyguanosine (8-OHdG) ELISA assay was used to quantify oxidative DNA damage in
      HCECs freshly isolated from ex vivo corneas. 8-OHdG immunostaining localized the
      sites of oxidative DNA damage in corneal wholemounts and cultured HCECs. To test
      whether oxidative stress induces oxidative DNA damage, HCECs cultured from young
      donors were treated with increasing concentrations of hydrogen peroxide
      (H(2)O(2)) and immunostained for 8-OHdG. To test the effect of oxidative stress
      on proliferative capacity, HCECs cultured from young donors were treated with
      H(2)O(2) and cell numbers determined by WST-8 assay. RESULTS: 8-OHdG levels were
      significantly higher (P = 0.0031) in the central endothelium of older donors than
      of young donors. Intense nuclear staining for 8-OHdG was observed in central
      endothelium of older, but not young, donors. The relative intensity of 8-OHdG in
      the nuclei of cultured HCECs was similar to that observed in ex vivo corneas.
      Treatment of cultured HCECs from young donors with increasing concentrations of
      H(2)O(2) resulted in a dose-dependent increase in nuclear 8-OHdG staining and a
      decrease in proliferative capacity similar to that observed in untreated HCECs
      from older donors. CONCLUSIONS: Age-dependent and topographical decreases in
      proliferative capacity observed in HCECs resulted, at least in part, from nuclear
      oxidative DNA damage.

PMID- 19117932
TI  - Mertk drives myosin II redistribution during retinal pigment epithelial
      phagocytosis.
AB  - PURPOSE: Mertk is a key phagocytic receptor in the immune, male reproductive, and
      visual systems. In the retinal pigment epithelium, Mertk is required for the
      daily ingestion of photoreceptor outer segment (OS) tips. Loss of Mertk function
      causes retinal degeneration in rats, mice, and humans; however, little is known
      about the mechanism by which Mertk regulates the ingestion phase of retinal
      pigment epithelial (RPE) phagocytosis. To address this, the authors sought
      proteins that associated with Mertk during OS phagocytosis. METHODS: Lysates of
      RPE-J cells challenged with OS for various times were immunoprecipitated with
      Mertk antibody. Potential interacting proteins were identified by mass
      spectrometry and characterized with confocal microscopy, pharmacologic
      inhibition, and siRNA knockdown coupled with an in vitro phagocytic assay in
      primary RPE cells. RESULTS: Myh9, the non-muscle myosin II-A heavy chain, was
      enriched in immunoprecipitates from OS-treated samples. Myosin II-A and II-B
      isoforms exhibited a striking redistribution in wild-type rat primary RPE cells
      challenged with OS, moving from the cell periphery to colocalize with ingested OS
      over time. In contrast, myosin II-A redistribution in response to OS was blunted
      in primary RPE cells from RCS rats, which lack functional Mertk. Wild-type rat
      primary RPE cells treated with the myosin II-specific inhibitor blebbistatin or
      myosin II siRNAs exhibited a significant phagocytic defect. CONCLUSIONS: Mertk
      mobilizes myosin II from the RPE cell periphery to sites of OS engulfment, where
      myosin II function is essential for the normal phagocytic ingestion of OS.

PMID- 19117933
TI  - Tight junction transmembrane protein claudin subtype expression and distribution
      in human corneal and conjunctival epithelium.
AB  - PURPOSE: The combination of the tight junction transmembrane protein claudin
      subtypes is one of the most important determinants of variations in the tightness
      of individual paired tight junction strands. The barrier function of corneal
      epithelium is much stronger than that of conjunctival epithelium. In this study,
      the expression and cellular distribution of claudin species in in vivo human
      corneal and conjunctival epithelium were investigated. METHODS: Reverse
      transcription-polymerase chain reaction was used to reveal the claudin mRNA.
      Immunohistochemistry was used to determine the tissue distribution of tight
      junction-related proteins and MUC5AC. RESULTS: Transcripts for claudin-1, -2, -3,
      -4, -7, -9, and -14 were identified in human corneal epithelium. Transcripts for
      claudin-1, -2, -4, -7, -9, -10, and -14 were identified in human conjunctival
      epithelium. By immunohistochemistry, claudin-1, -4, and -7 were found to be
      localized at the membrane of human corneal and conjunctival epithelial cells. In
      human conjunctival epithelium, claudin-10 staining was observed at several, but
      not all, apical epithelial cell-to-goblet cell junctions. CONCLUSIONS: Claudin-1,
      -4, and -7 are expressed in corneal and conjunctival epithelia. Claudin-10 is
      prominent at several junctions between apical epithelial cells and goblet cells
      in conjunctival epithelium. Except for claudin-10 expression in conjunctival
      epithelium, the claudin subtype expressions of corneal and conjunctival epithelia
      are similar. Therefore, there must be a difference between these two epithelial
      types with regard to the specific ratio of claudin subtypes expressed or their
      phosphorylation status. The distribution of goblet cells in conjunctival
      epithelium also influences the difference in barrier function.

PMID- 19117934
TI  - Age- and sex-related differences in contrast sensitivity in C57BL/6 mice.
AB  - PURPOSE: To measure contrast sensitivity in C57BL/6, the most commonly used mouse
      in behavioral neuroscience, and to study the effect of sex, age, and miotic drugs
      on the contrast sensitivity function. In addition, the authors tested a mutant in
      which plasticity in the cerebellum is impaired by expressing a protein kinase C
      inhibitor. This inhibitor is also expressed in the retina, possibly affecting
      vision. METHODS: The gain of the optokinetic reflex (OKR) decreases as stimuli
      become more difficult to see. Recording OKR gains evoked by moving sine gratings
      shows whether the stimulus was distinguished from a homogeneous background and
      how well the stimulus was distinguished. RESULTS: Female mice have lower OKR
      gains than male mice (both groups: n = 10, P = 0.001). A similar difference was
      observed between 4-month-old (n = 10) and 9-month-old (n = 5) C57Bl/6 mice (P =
      0.001). These differences could not be detected with earlier dichotomic tests.
      C57BL/6 mice are able to see contrasts as low as 1%, well below the previously
      reported 5% threshold. Pilocarpine had no significant effect on contrast
      sensitivity (both groups: n = 10, P = 0.89). Vision in L7-PKCi mutants was
      unaffected (both groups: n = 10, P = 0.82). CONCLUSIONS: OKR gains decrease as
      stimuli become more difficult to see, making the OKR a powerful tool to quantify
      contrast sensitivity. In C57BL/6 these response magnitudes vary greatly between
      sexes and between mice that differ only a few months in age. Therefore, it is
      important to match groups according to age and sex in experiments that require
      unimpaired vision. Otherwise, impaired vision can be misinterpreted as a learning
      or motor problem.

PMID- 19117935
TI  - Orbital fibroblasts from patients with thyroid-associated ophthalmopathy
      overexpress CD40: CD154 hyperinduces IL-6, IL-8, and MCP-1.
AB  - PURPOSE: Fibroblast diversity represents an emerging concept critical to our
      understanding of tissue inflammation, repair, and remodeling. Orbital fibroblasts
      heterogeneously display Thy-1 and exhibit unique phenotypic attributes that may
      explain the susceptibility of the human orbit to thyroid-associated
      ophthalmopathy (TAO). In the present study the authors investigated the role of
      CD40 ligation on macrophage chemoattractant protein-1 (MCP-1), IL-6, and IL-8
      expression in fibroblasts from patients with TAO. METHODS: Human orbital
      fibroblasts were cultured from tissues obtained with informed consent from
      patients with TAO and from patients undergoing surgery for other noninflammatory
      conditions. The fibroblasts were then examined by flow cytometry, microscopy, and
      cytokine assays. RESULTS: The authors report that orbital fibroblasts from
      patients with TAO expressed elevated levels of CD40. Surface CD40 could be
      further upregulated by IFN-gamma in TAO and control fibroblasts. This
      upregulation was mediated through Jak2 and could be blocked by dexamethasone and
      AG490, a powerful and specific inhibitor of tyrosine kinase. Treatment with
      CD154, the ligand for CD40, upregulated the expression of IL-6, IL-8, and MCP-1
      in TAO fibroblasts but failed to do so in control cultures. Thy-1(+) fibroblasts
      displayed higher CD40 levels than did their Thy-1(-) counterparts and were
      largely responsible for this cytokine production. IL-1beta also induced MCP-1, IL
      6, and IL-8 more vigorously in TAO-derived fibroblasts. CONCLUSIONS:
      Characterization of orbital fibroblasts and their differential expression of
      cytokines and receptors should prove invaluable in understanding the site
      specific nature of TAO and the development of specific therapies.

PMID- 19117936
TI  - Prediction model for prevalence and incidence of advanced age-related macular
      degeneration based on genetic, demographic, and environmental variables.
AB  - PURPOSE: The joint effects of genetic, ocular, and environmental variables were
      evaluated and predictive models for prevalence and incidence of AMD were
      assessed. METHODS: Participants in the multicenter Age-Related Eye Disease Study
      (AREDS) were included in a prospective evaluation of 1446 individuals, of which
      279 progressed to advanced AMD (geographic atrophy or neovascular disease) and
      1167 did not progress during 6.3 years of follow-up. For prevalent AMD, 509
      advanced cases were compared with 222 controls. Covariates for the incidence
      analysis included age, sex, education, smoking, body mass index (BMI), baseline
      AMD grade, and the AREDS vitamin-mineral treatment assignment. DNA specimens were
      evaluated for six variants in five genes related to AMD. Unconditional logistic
      regression analyses were performed for prevalent and incident advanced AMD. An
      algorithm was developed and receiver operating characteristic curves and C
      statistics were calculated to assess the predictive ability of risk scores to
      discriminate progressors from nonprogressors. RESULTS: All genetic polymorphisms
      were independently related to prevalence of advanced AMD, controlling for genetic
      factors, smoking, BMI, and AREDS treatment. Multivariate odds ratios (ORs) were
      3.5 (95% confidence interval [CI], 1.7-7.1) for CFH Y402H; 3.7 (95% CI, 1.6-8.4)
      for CFH rs1410996; 25.4 (95% CI, 8.6-75.1) for LOC387715 A69S (ARMS2); 0.3 (95%
      CI, 0.1-0.7) for C2 E318D; 0.3 (95% CI, 0.1-0.5) for CFB; and 3.6 (95% CI, 1.4
      9.4) for C3 R102G, comparing the homozygous risk/protective genotypes to the
      referent genotypes. For incident AMD, all these variants except CFB were
      significantly related to progression to advanced AMD, after controlling for
      baseline AMD grade and other factors, with ORs from 1.8 to 4.0 for presence of
      two risk alleles and 0.4 for the protective allele. An interaction was seen
      between CFH402H and treatment, after controlling for all genotypes. Smoking was
      independently related to AMD, with a multiplicative joint effect with genotype on
      AMD risk. The C statistic for the full model with all variables was 0.831 for
      progression to advanced AMD. CONCLUSIONS: Factors reflective of nature and
      nurture are independently related to prevalence and incidence of advanced AMD,
      with excellent predictive power.

PMID- 19117937
TI  - Posterior juxtascleral infusion of modified triamcinolone acetonide formulation
      for refractory diabetic macular edema: one-year follow-up.
AB  - PURPOSE: To evaluate prospectively the efficacy and safety of posterior
      juxtascleral infusion of a new formulation of triamcinolone acetonide for
      refractory diffuse diabetic macular edema. METHODS: This was an interventional
      case series. Twenty-two consecutive eyes of 18 patients with refractory diffuse
      diabetic macular edema were included in the study. Each patient underwent a
      complete ophthalmic examination, including optical coherence tomography (OCT) and
      digital fluorescein angiography (FA). All patients received a suspension of 40 mg
      triamcinolone acetonide, 20 mg sodium chondroitin sulfate, and 15 mg sodium
      hyaluronate (1.5 mL), delivered posteriorly through a conjunctival and Tenon's
      incision. All patients completed the 1-year follow-up. RESULTS: On average,
      studied eyes received 1.5 treatments. Mean preoperative foveal thickness (+/-SD)
      and visual acuity (+/-SD) were 474.2 +/- 136.6 microm and 0.6 +/- 0.37 logarithm
      of the minimum angle of resolution (logMAR), respectively. The central foveal
      thickness was significantly reduced from baseline at every follow-up visit (P <
      0.001). Mean (+/-SD) reductions in macular thickness were 136 +/- 108 microm at 1
      week and 128 +/- 122 microm after 1 year of follow-up. Mean (+/-SD) improvement
      in visual acuity at 12 months was 0.15 +/- 0.21 logMAR (P = 0.008). Visual acuity
      improvement of one or more lines and three or more lines were observed in 14
      (63.6%) and 6 (27.3%) eyes, respectively. Seven eyes (31.8%) required topical
      treatment due to a significant intraocular pressure increase. CONCLUSIONS:
      Posterior juxtascleral infusion of a new formulation of triamcinolone acetonide
      is an effective treatment for diffuse diabetic macular edema unresponsive to
      conventional grid laser photocoagulation. A randomized, larger study is
      warranted.

PMID- 19117938
TI  - Acid-sensing ion channel 3 in retinal function and survival.
AB  - PURPOSE: Changes in extracellular pH occur in the retina and directly affect
      retinal activity and phototransduction. The authors analyzed the expression in
      rodent retina of ASIC3, a sensor of extracellular acidosis, and used ASIC3
      knockout mice to explore its role in retinal function and survival. METHODS: The
      expression and the role of ASIC3 were examined by immunolocalization and by
      comparing retinas from wild-type and knockout mice at different ages through
      electroretinography, retinal histology (light and electron microscopy),
      expression of glial fibrillary acidic protein (GFAP), analysis of cell apoptosis
      (TUNEL assay), and patch-clamp recordings in primary cultures of retinal ganglion
      cells (RGCs). RESULTS: ASIC3 is present in the rod inner segment of
      photoreceptors and in horizontal and some amacrine cells. ASIC3 is also detected
      in RGCs but does not significantly contribute to ASIC currents recorded in
      cultured RGCs. At 2 to 3 months, knockout mice experience a 19% enhancement of
      scotopic electroretinogram a-wave amplitude and a concomitant increase of b-wave
      amplitude without alteration of retinal structure. Older (8-month-old) knockout
      mice have 69% and 64% reductions in scotopic a- and b-waves, respectively, and
      reductions in oscillatory potential amplitudes associated with complete
      disorganization of the retina and degenerating rod inner segments. GFAP and TUNEL
      staining performed at 8 and 12 months of age revealed an upregulation of GFAP
      expression in Muller cells and the presence of apoptotic cells in the inner and
      outer retina. CONCLUSIONS: Inactivation of ASIC3 enhances visual transduction at
      2 to 3 months but induces late-onset rod photoreceptor death, suggesting an
      important role for ASIC3 in maintaining retinal integrity.

PMID- 19117939
TI  - Low intensity shear stress increases endothelial ELR+ CXC chemokine production
      via a focal adhesion kinase-p38{beta} MAPK-NF-{kappa}B pathway.
AB  - CXC chemokines with a glutamate-leucine-arginine (ELR) tripeptide motif (ELR(+)
      CXC chemokines) play an important role in leukocyte trafficking into the tissues.
      For reasons that are not well elucidated, circulating leukocytes are recruited
      into the tissues mainly in small vessels such as capillaries and venules. Because
      ELR(+) CXC chemokines are important mediators of endothelial-leukocyte
      interaction, we compared chemokine expression by microvascular and aortic
      endothelium to investigate whether differences in chemokine expression by various
      endothelial types could, at least partially, explain the microvascular
      localization of endothelial-leukocyte interaction. Both in vitro and in vivo
      models indicate that ELR(+) CXC chemokine expression is higher in microvascular
      endothelium than in aortic endothelial cells. These differences can be explained
      on the basis of the preferential activation of endothelial chemokine production
      by low intensity shear stress. Low shear activated endothelial ELR(+) CXC
      chemokine production via cell surface heparan sulfates, beta(3)-integrins, focal
      adhesion kinase, the mitogen-activated protein kinase p38beta, mitogen- and
      stress-associated protein kinase-1, and the transcription factor.

PMID- 19117940
TI  - The HLA-DRalpha chain is modified by polyubiquitination.
AB  - Ubiquitination plays a major role in regulating cell surface and intracellular
      localization of major histocompatibility complex class II molecules. Two E3
      ligases, MARCH I and MARCH VIII, have been shown to polyubiquitinate lysine
      residue 225 in the cytoplasmic tail of I-Abeta and HLA-DRbeta. We show that
      lysine residue 219 in the cytoplasmic tail of DRalpha is also subject to
      polyubiquitination. Each chain of the HLA-DR heterodimer is independently
      recognized and ubiquitinated, but DRbeta is more extensively modified. In the
      cytoplasmic tail of DRbeta lysine, residue 225 is the only residue that is
      absolutely required for ubiquitination; all other residues can be deleted or
      substituted without loss of function. In contrast, although lysine 219 is
      absolutely required for modification of DRalpha, other features of the DRalpha
      tail act to limit the extent of ubiquitination.

PMID- 19117941
TI  - The eukaryotic ribosome: current status and challenges.
AB  - Despite having been identified first, their greater degree of complexity has
      resulted in our understanding of eukaryotic ribosomes lagging behind that of
      their bacterial and archaeal counterparts. A much more complicated biogenesis
      program results in ribosomes that are structurally, biochemically, and
      functionally more complex. However, recent advances in molecular genetics and
      structural biology are helping to reveal the intricacies of the eukaryotic
      ribosome and to address many longstanding questions regarding its many roles in
      the regulation of gene expression.

PMID- 19117942
TI  - Head and rod 1 interactions in vimentin: identification of contact sites,
      structure, and changes with phosphorylation using site-directed spin labeling and
      electron paramagnetic resonance.
AB  - We have used site-directed spin labeling (SDSL) and electron paramagnetic
      resonance (EPR) to identify residues 17 and 137 as sites of interaction between
      the head domain and rod domain 1A of the intermediate filament protein vimentin.
      This interaction was maximal when compared with the spin labels placed at up- and
      downstream positions in both head and rod regions, indicating that residues 17
      and 137 were the closest point of interaction in this region. SDSL EPR
      characterization of residues 120-145, which includes the site of head contact
      with rod 1A, reveals that this region exhibits the heptad repeat pattern
      indicative of alpha-helical coiled-coil structure, but that this heptad repeat
      pattern begins to decay near residue 139, suggesting a transition out of coiled
      coil structure. By monitoring the spectra of spin labels placed at the 17 and 137
      residues during in vitro assembly, we show that 17-137 interaction occurs early
      in the assembly process. We also explored the effect of phosphorylation on the 17
      137 interaction and found that phosphorylation-induced changes affected the head
      head interaction (17-17) in the dimer, without significantly influencing the rod
      rod (137-137) and head-rod (17-137) interactions in the dimer. These data provide
      the first direct evidence for, and location of, head-rod interactions in
      assembled intermediate filaments, as well as direct evidence of coiled-coil
      structure in rod 1A. Finally, the data identify changes in the structure in this
      region following in vitro phosphorylation.

PMID- 19117943
TI  - Zinc can play chaperone-like and inhibitor roles during import of mitochondrial
      small Tim proteins.
AB  - Zinc is an essential cofactor required for the function of approximately 8% of
      the yeast and 10% of the human proteome. All of the "small Tim" proteins of the
      mitochondrial intermembrane space contain a strictly conserved "twin CX(3)C" zinc
      finger motif, which can bind zinc ions in the Cys-reduced form. We have shown
      previously that although disulfide bond formation is essential for the function
      of these proteins in mitochondria, only reduced proteins can be imported into
      mitochondria (Lu, H., Allen, S., Wardleworth, L., Savory, P., and Tokatlidis, K.
      (2004) J. Biol. Chem. 279, 18952-18958 and Morgan, B., and Lu, H. (2008) Biochem.
      J. 411, 115-122). However, the role of zinc during the import of these proteins
      is unclear. This study shows that the function of zinc is complex. It can play a
      thiol stabilizer role preventing oxidative folding of the small Tim proteins and
      maintaining the proteins in an import-competent form. On the other hand, zinc
      bound forms cannot be imported into mitochondria efficiently. Furthermore, our
      results show that zinc is a powerful inhibitor of Erv1, an essential component of
      the import pathway used by the small Tim proteins. We propose that zinc plays a
      chaperone-like role in the cytosol during biogenesis of the small Tim proteins
      and that the proteins are imported into mitochondria through the apo-forms.

PMID- 19117944
TI  - Disruption of a Plasmodium falciparum multidrug resistance-associated protein
      (PfMRP) alters its fitness and transport of antimalarial drugs and glutathione.
AB  - ATP-binding cassette transporters play an important role in drug resistance and
      nutrient transport. In the human malaria parasite Plasmodium falciparum, a
      homolog of the human p-glycoprotein (PfPgh-1) was shown to be involved in
      resistance to several drugs. More recently, many transporters were associated
      with higher IC(50) levels in responses to chloroquine (CQ) and quinine (QN) in
      field isolates. Subsequent studies, however, could not confirm the associations,
      although inaccuracy in drug tests in the later studies could contribute to the
      lack of associations. Here we disrupted a gene encoding a putative multidrug
      resistance-associated protein (PfMRP) that was previously shown to be associated
      with P. falciparum responses to CQ and QN. Parasites with disrupted PfMRP
      (W2/MRPDelta) could not grow to a parasitemia higher than 5% under normal culture
      conditions, possibly because of lower efficiency in removing toxic metabolites.
      The W2/MRPDelta parasite also accumulated more radioactive glutathione, CQ, and
      QN and became more sensitive to multiple antimalarial drugs, including CQ, QN,
      artemisinin, piperaquine, and primaquine. PfMRP was localized on the parasite
      surface membrane, within membrane-bound vesicles, and along the straight side of
      the D-shaped stage II gametocytes. The results suggest that PfMRP plays a role in
      the efflux of glutathione, CQ, and QN and contributes to parasite responses to
      multiple antimalarial drugs, possibly by pumping drugs outside the parasite.

PMID- 19117945
TI  - mDia2 shuttles between the nucleus and the cytoplasm through the importin
      {alpha}/{beta}- and CRM1-mediated nuclear transport mechanism.
AB  - Mammalian homolog of Drosophila diaphanous (mDia) consisting of three isoforms,
      mDia1, mDia2, and mDia3, is an effector of Rho GTPases that catalyzes actin
      nucleation and polymerization. Although the mDia actions on actin dynamics in the
      cytoplasm have been well studied, whether mDia accumulates and functions in the
      nucleus remains largely unknown. Given the presence of actin and actin-associated
      proteins in the nucleus, we have examined nuclear localization of mDia isoforms.
      We expressed each of mDia isoforms as a green fluorescent protein fusion protein
      and examined their localization. Although all the mDia isoforms were localized
      predominantly in the cytoplasm under the steady-state conditions, mDia2 and not
      mDia1 or mDia3 accumulated extensively in the nucleus upon treatment with
      leptomycin B (LMB), an inhibitor of CRM1-dependent nuclear export. The LMB
      induced nuclear accumulation was confirmed for endogenous mDia2 by using an
      antibody specific to mDia2. Studies using green fluorescent protein fusions of
      various truncation mDia2 mutants and point mutants of some of these proteins
      identified a functional nuclear localization signal in the N terminus of mDia2
      and at least one functional nuclear export signal in the C terminus. The nuclear
      localization signal of mDia2 bound to importin-alpha and was imported into the
      nucleus by importin-alpha/beta complex in an in vitro transport assay.
      Consistently, depletion of importin-beta with RNA interference suppressed the LMB
      induced nuclear localization of endogenous mDia2. These results suggest that
      mDia2 continuously shuttles between the nucleus and the cytoplasm using specific
      nuclear transport machinery composing of importin-alpha/beta and CRM1.

PMID- 19117946
TI  - Flexibility in anaerobic metabolism as revealed in a mutant of Chlamydomonas
      reinhardtii lacking hydrogenase activity.
AB  - The green alga Chlamydomonas reinhardtii has a network of fermentation pathways
      that become active when cells acclimate to anoxia. Hydrogenase activity is an
      important component of this metabolism, and we have compared metabolic and
      regulatory responses that accompany anaerobiosis in wild-type C. reinhardtii
      cells and a null mutant strain for the HYDEF gene (hydEF-1 mutant), which encodes
      an [FeFe] hydrogenase maturation protein. This mutant has no hydrogenase activity
      and exhibits elevated accumulation of succinate and diminished production of CO2
      relative to the parental strain during dark, anaerobic metabolism. In the absence
      of hydrogenase activity, increased succinate accumulation suggests that the cells
      activate alternative pathways for pyruvate metabolism, which contribute to
      NAD(P)H reoxidation, and continued glycolysis and fermentation in the absence of
      O2. Fermentative succinate production potentially proceeds via the formation of
      malate, and increases in the abundance of mRNAs encoding two malate-forming
      enzymes, pyruvate carboxylase and malic enzyme, are observed in the mutant
      relative to the parental strain following transfer of cells from oxic to anoxic
      conditions. Although C. reinhardtii has a single gene encoding pyruvate
      carboxylase, it has six genes encoding putative malic enzymes. Only one of the
      malic enzyme genes, MME4, shows a dramatic increase in expression (mRNA
      abundance) in the hydEF-1 mutant during anaerobiosis. Furthermore, there are
      marked increases in transcripts encoding fumarase and fumarate reductase, enzymes
      putatively required to convert malate to succinate. These results illustrate the
      marked metabolic flexibility of C. reinhardtii and contribute to the development
      of an informed model of anaerobic metabolism in this and potentially other algae.

PMID- 19117947
TI  - Cdk2ap1 is required for epigenetic silencing of Oct4 during murine embryonic stem
      cell differentiation.
AB  - Oct4 is a known master regulator of stem cell renewal and differentiation.
      Expression of Oct4 during differentiation is regulated by promoter methylation by
      the nucleosome remodeling and histone deacetylation (NuRD) complex. Here, we show
      that Cdk2ap1, a negative regulator of Cdk2 function and cell cycle, promotes Oct4
      promoter methylation during murine embryonic stem cell differentiation to down
      regulate Oct4 expression. We further show that this repressor function of Cdk2ap1
      is dependent on its physical interaction with the methyl DNA-binding protein,
      Mbd3. Our data support a potential molecular link between the known
      differentiation promoters, including bone morphogenetic proteins and transforming
      growth factor signaling, and embryonic stem cell differentiation.

PMID- 19117948
TI  - PTEN, stem cells, and cancer stem cells.
AB  - Like normal stem cells, "cancer stem cells" have the capacity for indefinite
      proliferation and generation of new cancerous tissues through self-renewal and
      differentiation. Among the major intracellular signaling pathways, WNT, SHH, and
      NOTCH are known to be important in regulating normal stem cell activities, and
      their alterations are associated with tumorigenesis. It has become clear recently
      that PTEN (phosphatase and tensin homologue) is also critical for stem cell
      maintenance and that PTEN loss can cause the development of cancer stem cells and
      ultimately tumorigenesis.

PMID- 19117949
TI  - Primary steps of the Na+-translocating NADH:ubiquinone oxidoreductase catalytic
      cycle resolved by the ultrafast freeze-quench approach.
AB  - The Na(+)-translocating NADH:ubiquinone oxidoreductase (Na(+)-NQR) is a component
      of respiratory chain of various bacteria, and it generates a redox-driven
      transmembrane electrochemical Na(+) potential. Primary steps of the catalytic
      cycle of Na(+)-NQR from Vibrio harveyi were followed by the ultrafast freeze
      quench approach in combination with conventional stopped-flow technique. The
      obtained sequence of events includes NADH binding ( approximately 1.5 x 10(7) m(
      1) s(-1)), hydride ion transfer from NADH to FAD ( approximately 3.5 x 10(3) s(
      1)), and partial electron separation and formation of equivalent fractions of
      reduced 2Fe-2S cluster and neutral semiquinone of FAD ( approximately 0.97 x
      10(3) s(-1)). In the last step, a quasi-equilibrium is approached between the two
      states of FAD: two-electron reduced (50%) and one-electron reduced (the other
      50%) species. The latter, neutral semiquinone of FAD, shares the second electron
      with the 2Fe-2S center. The transient midpoint redox potentials for the cofactors
      obtained during the fast kinetics measurements are very different from ones
      achieved during equilibrium redox titration and show that the functional states
      of the enzyme realized during its turning over cannot be modeled by the
      equilibrium approach.

PMID- 19117950
TI  - Atrogin-1/MAFbx enhances simulated ischemia/reperfusion-induced apoptosis in
      cardiomyocytes through degradation of MAPK phosphatase-1 and sustained JNK
      activation.
AB  - Atrogin-1/MAFbx is a major atrophy-related E3 ubiquitin ligase that is expressed
      specifically in striated muscle. Although the contribution of atrogin-1 to
      cardiac and muscle hypertrophy/atrophy has been examined extensively, it remains
      unclear whether atrogin-1 plays an essential role in the simulated
      ischemia/reperfusion-induced apoptosis of primary cardiomyocytes. Here we showed
      that atrogin-1 markedly enhanced ischemia/reperfusion-induced apoptosis in
      cardiomyocytes via activation of JNK signaling. Overexpression of atrogin-1
      increased phosphorylation of JNK and c-Jun and decreased phosphorylation of
      Foxo3a. In addition, atrogin-1 decreased Bcl-2, increased Bax, and enhanced the
      activation of caspases. Furthermore, JNK inhibitor SP600125 markedly blocked the
      effect of atrogin-1 on cell apoptosis and the expression of apoptotic-related
      proteins and caspases. Importantly, atrogin-1 induced sustained activation of JNK
      through a mechanism that involved degradation of MAPK phosphatase-1 (MKP-1)
      protein. Atrogin-1 interacted with and triggered MKP-1 for ubiquitin-mediated
      degradation. In contrast, proteasome inhibitors markedly blocked the degradation
      of MKP-1. Taken together, these results demonstrate that atrogin-1 promotes
      degradation of MKP-1 through the ubiquitin-proteasome pathway, thereby leading to
      persistent activation of JNK signaling and further cardiomyocyte apoptosis
      following ischemia/reperfusion injury.

PMID- 19117951
TI  - Interaction of APC/C-E3 ligase with Swi6/HP1 and Clr4/Suv39 in heterochromatin
      assembly in fission yeast.
AB  - Heterochromatin assembly in fission yeast is initiated by binding of Swi6/HP1 to
      the Lys-9-dimethylated H3 followed by spreading via cooperative recruitment of
      Swi6/HP1. Recruitment of Cohesin by Swi6/HP1 further stabilizes the
      heterochromatin structure and integrity. Subsequently, polyubiquitylation of Cut2
      by anaphase-promoting complex-cyclosome (APC/C)-ubiquitin-protein isopeptide
      ligase (E3 ligase) followed by degradation of Cut2 releases Cut1, which cleaves
      the Rad21 subunit of Cohesin, facilitating sister chromatid separation during
      mitosis. Here, we demonstrate a surprising role of APC/C in assembly of
      heterochromatin and silencing at mating type, centromere, and ribosomal DNA loci.
      Coincidentally with the loss of silencing, recruitment of Swi6, H3-Lys-9-Me2, and
      Clr4 at dg-dh repeats at cen1 and the K region of mat locus is abrogated in
      mutants cut4, cut9, and nuc2. Surprisingly, both Cut4 and Cut9 are also highly
      enriched at these regions in wild type and depleted in swi6Delta mutant. Cut4 and
      Cut9 interact directly with Swi6/HP1 and Clr4, whereas the mutant Cut4 does not,
      suggesting that a direct physical interaction of APC subunits Cut4 and Cut9 with
      Swi6 and Clr4 is instrumental in heterochromatin assembly. The silencing defect
      in APC mutants is causally related to ubiquitylation activity of APC-E3 ligase.
      Like swi6 mutant, APC mutants are also defective in Cohesin recruitment and
      exhibit defects like lagging chromosomes, chromosome loss, and aberrant
      recombination in the mat region. In addition, APC mutants exhibit a bidirectional
      expression of dh repeats, suggesting a role in the RNA interference pathway.
      Thus, APC and heterochromatin proteins Swi6 and Clr4 play a mutually cooperative
      role in heterochromatin assembly, thereby ensuring chromosomal integrity,
      inheritance, and segregation during mitosis and meiosis.

PMID- 19117952
TI  - Lipid droplet biogenesis induced by stress involves triacylglycerol synthesis
      that depends on group VIA phospholipase A2.
AB  - This work investigates the metabolic origin of triacylglycerol (TAG) formed
      during lipid droplet (LD) biogenesis induced by stress. Cytotoxic inhibitors of
      fatty acid synthase induced TAG synthesis and LD biogenesis in CHO-K1 cells, in
      the absence of external sources of fatty acids. TAG synthesis was required for LD
      biogenesis and was sensitive to inhibition and down-regulation of the expression
      of group VIA phospholipase A(2) (iPLA(2)-VIA). Induction of stress with acidic
      pH, C(2)-ceramide, tunicamycin, or deprivation of glucose also stimulated TAG
      synthesis and LD formation in a manner dependent on iPLA(2)-VIA. Overexpression
      of the enzyme enhanced TAG synthesis from endogenous fatty acids and LD
      occurrence. During stress, LD biogenesis but not TAG synthesis required
      phosphorylation and activation of group IVA PLA(2) (cPLA(2)alpha). The results
      demonstrate that iPLA(2)-VIA provides fatty acids for TAG synthesis while
      cPLA(2)alpha allows LD biogenesis. LD biogenesis during stress may be a survival
      strategy, recycling structural phospholipids into energy-generating substrates.

PMID- 19117953
TI  - Crystal structure of procaspase-1 zymogen domain reveals insight into
      inflammatory caspase autoactivation.
AB  - One key event in inflammatory signaling is the activation of the initiator
      caspase, procaspase-1. Presented here is the crystal structure of the procaspase
      1 zymogen without its caspase recruitment domain solved to 2.05 A. Although the
      isolated domain is monomeric in solution, the protein appeared dimeric in
      crystals. The loop arrangements in the dimer provide insight into the first
      autoproteolytic events that occur during activation by oligomerization.
      Additionally, in contrast to other caspases, we demonstrate that autoproteolysis
      at the second cleavage site, Asp316, is necessary for conversion to a stable
      dimer in solution. Critical elements of secondary structure are revealed in the
      crystal structure that explain why a dimeric protein is favored after proteolysis
      at this aspartic acid. Dimer stabilization is concurrent with a 130-fold increase
      in kcat, the sole contributing kinetic factor to an activated and efficient
      mediator of inflammation.

PMID- 19117954
TI  - Fibroblast growth factor receptor 2 promotes osteogenic differentiation in
      mesenchymal cells via ERK1/2 and protein kinase C signaling.
AB  - Mesenchymal stem cells (MSCs) are able to differentiate into several lineages
      including osteoblasts. The signaling mechanisms involved in the osteogenic
      differentiation of MSCs are however not fully understood. We investigated the
      role of fibroblast growth factor receptor 2 (FGFR2) in osteoblast committment and
      differentiation of murine mesenchymal C3H10T1/2 cells stably transfected with
      wild type (WT) or activated FGFR2 due to Apert S252W genetic mutation (MT). WT
      FGFR2 slightly increased, whereas MT FGFR2 strongly increased, FGFR2 tyrosine
      phosphorylation, indicating activation of the receptor. WT and MT FGFR2 increased
      C3H10T1/2 cell proliferation but not survival. Both WT and MT FGFR2 increased
      early and late osteoblast gene expression and matrix mineralization. Forced
      expression of WT and MT FGFR2 also increased osteoblast gene expression in MC3T3
      E1 calvaria osteoblasts. In both cell types, MT FGFR2 was more effective than WT
      FGFR2. In contrast, WT and MT FGFR2 decreased adipocyte differentiation of
      C3H10T1/2 cells. WT and MT FGFR2 induced ERK1/2 but not JNK or PI3K/AKT
      phosphorylation. MT, but not WT, also increased protein kinase C (PKC) activity.
      Pharmacological inhibition of ERK1/2 prevented cell proliferation induced by WT
      and MT FGFR2. Using dominant-negative ERK and PKCalpha vectors, we demonstrated
      that WT and MT FGFR2 promoted osteoblast gene expression through ERK1/2 and
      PKCalpha signaling, respectively. This study identifies FGFR2 as a novel
      regulatory molecule that promotes osteogenic differentiation in murine MSCs. The
      promoting effect of WT and MT FGFR2 is mediated by ERK1/2 and PKCalpha pathways
      that play essential and distinct roles in FGFR2-induced osteogenic
      differentiation of mesenchymal cells.

PMID- 19117955
TI  - Structural basis of focal adhesion localization of LIM-only adaptor PINCH by
      integrin-linked kinase.
AB  - The LIM-only adaptor PINCH (the particularly interesting cysteine- and histidine
      rich protein) plays a pivotal role in the assembly of focal adhesions (FAs),
      supramolecular complexes that transmit mechanical and biochemical information
      between extracellular matrix and actin cytoskeleton, regulating diverse cell
      adhesive processes such as cell migration, cell spreading, and survival. A key
      step for the PINCH function is its localization to FAs, which depends critically
      on the tight binding of PINCH to integrin-linked kinase (ILK). Here we report the
      solution NMR structure of the core ILK.PINCH complex (28 kDa, K(D) approximately
      68 nm) involving the N-terminal ankyrin repeat domain (ARD) of ILK and the first
      LIM domain (LIM1) of PINCH. We show that the ILK ARD exhibits five sequentially
      stacked ankyrin repeat units, which provide a large concave surface to grip the
      two contiguous zinc fingers of the PINCH LIM1. The highly electrostatic interface
      is evolutionally conserved but differs drastically from those of known ARD and
      LIM bound to other types of protein domains. Consistently mutation of a hot spot
      in LIM1, which is not conserved in other LIM domains, disrupted the PINCH binding
      to ILK and abolished the PINCH targeting to FAs. These data provide atomic
      insight into a novel modular recognition and demonstrate how PINCH is
      specifically recruited by ILK to mediate the FA assembly and cell-extracellular
      matrix communication.

PMID- 19117957
TI  - Calculation of the indoor gamma dose rate distribution due to building materials
      in the Netherlands.
AB  - In this study, a model to determine the indoor absorbed dose rate in air due to
      building materials is applied to a representative set of 1336 Dutch dwellings of
      which the areas occupied by the various kinds of building material are well
      documented. Using a Monte Carlo method, the building material and housing data
      are combined with activity concentrations and densities of 90 samples of building
      material. From (100,000) repeated calculations according to the model, the
      distribution of the absorbed dose rate in Dutch livings is computed. The outcomes
      are compared with those of earlier national measuring campaigns on the indoor
      dose rate. When corrected for cosmic and terrestrial radiation, a similar
      distribution of the indoor dose rate is found with an average value within 5% of
      that found by measurements. A sensitivity analysis revealed that the three most
      influential input parameters of the model are the density and thickness of the
      construction parts, the presence of doors and windows and attenuation by the
      inner cavity wall.

PMID- 19117956
TI  - Structural analysis of the DNA-binding domain of the Helicobacter pylori response
      regulator ArsR.
AB  - The Helicobacter pylori ArsS-ArsR two-component signal transduction system,
      comprised of a sensor histidine kinase (ArsS) and a response regulator (ArsR),
      allows the bacteria to regulate gene expression in response to acidic pH. We
      expressed and purified the full-length ArsR protein and the DNA-binding domain of
      ArsR (ArsR-DBD), and we analyzed the tertiary structure of the ArsR-DBD using
      solution nuclear magnetic resonance (NMR) methods. Both the full-length ArsR and
      the ArsR-DBD behaved as monomers in size exclusion chromatography experiments.
      The structure of ArsR-DBD consists of an N-terminal four-stranded beta-sheet, a
      helical core, and a C-terminal beta-hairpin. The overall tertiary fold of the
      ArsR-DBD is most closely related to DBD structures of the OmpR/PhoB subfamily of
      bacterial response regulators. However, the orientation of the N-terminal beta
      sheet with respect to the rest of the DNA-binding domain is substantially
      different in ArsR compared with the orientation in related response regulators.
      Molecular modeling of an ArsR-DBD-DNA complex permits identification of protein
      elements that are predicted to bind target DNA sequences and thereby regulate
      gene transcription in H. pylori.

PMID- 19117958
TI  - Aptamers influence the hemostatic system by activating the intrinsic coagulation
      pathway in an in vitro Chandler-Loop model.
AB  - One class of oligonucleotides with a high potential for use in medical
      applications is short nucleic acids, widely known as aptamers. Although several
      aptamers are already being used clinically, there are very few studies dealing
      with the impact aptamers have on the hemostatic system. In this study, we have
      performed a comprehensive evaluation of the hemostatic system including
      coagulation, platelets, complement, and inflammatory activation by using
      different aptamer concentrations and fresh human whole blood in a well
      established flow model. We found that single-stranded aptamers did not have a
      negative influence on platelets, complement, or inflammation but were able to
      activate factor XII, kallikrein, and prothrombin in a concentration-dependent
      manner. Consequently, the influence of aptamers on the coagulation system should
      be taken into consideration before the use of any aptamer-based drugs in
      patients.

PMID- 19117959
TI  - Optimal dosing of intravenous unfractionated heparin bolus in transient ischemic
      attack or stroke.
AB  - Early initiation of heparin therapy for treatment of stroke is not only
      associated with an improved outcome, but also with the risk of hemorrhagic
      transformation. We compared the efficacy of three unfractionated heparin bolus
      regimens (0 U/kg, 30 U/kg, or 80 U/kg) in achieving a therapeutic activated
      partial thromboplastin time over the first 6-hour period in a cohort of 54
      patients admitted with transient ischemic attack or stroke. Patients treated with
      the low bolus dose (30 U/kg) were more often within the therapeutic range for
      activated partial thromboplastin time at two hours after the initial bolus than
      patients treated with the other regimens. The percentage of therapeutic activated
      partial thromboplastin time results within the first six hours of treatment was
      greater in the group treated with the low bolus dose. Using the low bolus dose
      may reduce complication rates and improve clinical outcomes in the future
      clinical trials.

PMID- 19117960
TI  - Catheter-related thrombosis: biological and clinical evidence for risk with
      currently available anticoagulants.
AB  - Anticoagulants used during percutaneous coronary intervention (PCI) should not
      only prevent coronary events, but also minimize the risk of periprocedural
      complications. Current anticoagulation therapies for PCI include unfractionated
      heparin (UFH), enoxaparin, fondaparinux, and bivalirudin. UFH and enoxaparin have
      good efficacy and safety profiles in PCI; furthermore, associated periprocedural
      complications such as catheter thrombosis are rare. Although newer anticoagulants
      seem safe and effective in patients with acute coronary syndrome, clinical trial
      data suggest that some pure factor Xa (FXa) inhibitors are associated with
      increased rates of catheter thrombosis, compared with heparin-based agents.
      Experimental systems show that polytherapeutic agents, including UFH and
      enoxaparin, are more effective anticoagulants than certain single-target agents.
      More studies are needed to assess whether catheter thrombosis is a class-, drug-,
      or dose-related effect, and how best to prevent it. Future trials should report
      the rates of periprocedural complications when assessing the safety of novel
      anticoagulation therapies in PCI.

PMID- 19117962
TI  - SASAT (South Asian Society on Atherosclerosis & Thrombosis) proposal for
      regulatory guidelines for generic low-molecular weight heparins (LMWHs).

PMID- 19117963
TI  - Gastrointestinal complications after 3 months of dual antiplatelet therapy for
      drug-eluting stents as assessed by wireless capsule endoscopy.
AB  - Little is known about the frequency of symptomatic and asymptomatic
      gastrointestinal complications of dual antiplatelet therapy. We recruited 30
      patients between 18 and 80 years who were started on aspirin and clopidogrel
      following percutaneous coronary intervention with drug-eluting stents. We
      hypothesized that the 3 months of dual antiplatelet therapy would be associated
      with frequent upper gastrointestinal endoscopic abnormalities. Patients were
      followed with weekly phone calls to inquire about the new gastrointestinal
      symptoms and after a minimum of 80 days, their upper gastrointestinal mucosa was
      visualized with PillCam ESO wireless capsule endoscopy. 18 (90%) of the 20
      successful wireless capsule endoscopies revealed at least 1 type of
      gastrointestinal mucosal lesion. Gastric erosions (n = 14, 70%) were the most
      common abnormality. We believe this is the first noninvasive endoscopic study of
      gastrointestinal complications of dual antiplatelet therapy in patients who
      undergo percutaneous coronary intervention with drug-eluting stents. Future
      studies should expand on our observations to determine whether prophylaxis with
      proton pump inhibitors is warranted.

PMID- 19117964
TI  - Assessment of fibrinolytic activity by measuring the lysis time of a tissue
      factor-induced clot: a feasibility evaluation.
AB  - A clot lysis time assay in which a tissue factor-induced fibrin clot is lysed by
      exogenously added tissue plasminogen activator has been recently reported. We
      evaluated the feasibility of clot lysis time in a routine hemostasis laboratory,
      and its correlation with thrombin activatable fibrinolysis inhibitor and
      plasminogen activator inhibitor-1 levels and changes with aging in 185 healthy
      participants. Clot lysis time was assessed by monitoring changes in turbidity
      during clot formation and subsequent lysis using a computerized kinetic
      spectrophotometric microtiter plate. After preliminary experiments, 100 and 160
      ng/mL tissue plasminogen activator concentrations were chosen for the study. Clot
      lysis time was calculated by a new mathematical analysis of the lysis curve based
      on discrete derivative. Clot lysis time, thrombin activatable fibrinolysis
      inhibitor, and plasminogen activator inhibitor-1 plasma levels showed a normal
      distribution. For both concentrations of tissue plasminogen activator, clot lysis
      time progressively increased with increase in age (P < .0001) and was
      significantly correlated with thrombin activatable fibrinolysis inhibitor
      antigen, thrombin activatable fibrinolysis inhibitor activity, and plasminogen
      activator inhibitor-1 antigen (at least P < .01). During linear regression
      analysis, thrombin activatable fibrinolysis inhibitor and plasminogen activator
      inhibitor-1 antigen were found to significantly influence clot lysis time (at
      least P < .01). Clot lysis time determination has a good laboratory performance.
      Our new method of calculation is independent of the time of reading and allows a
      more accurate and consistent detection of both short and prolonged lysis times.
      Our data suggest the feasibility of the use of this test in the work of routine
      hemostasis laboratory.

PMID- 19117965
TI  - Effect of sulodexide on plasma transforming growth factor-beta1 in healthy
      volunteers.
AB  - It is unknown whether the glycosaminoglycan drug sulodexide interferes with
      transforming growth factor-beta1--a member of heparin-binding family and a potent
      regulator of human biology and diseases. Hence, a 2-week pilot study was
      performed in 11 healthy men. Sulodexide was initially administered intravenously
      in a single dose, then--orally for 12 days and--again intravenously on study
      completion. Initial injection had no effect on activated form of the growth
      factor measured in plasma after 10 and 120 min; no change was also observed after
      120 min from drug ingestion on day 7. On final intravenous administration, the
      growth factor levels increased by almost 60% after 10 min and remained elevated;
      the 120-min levels directly correlated with sulodexide dosage. Baseline cytokine
      levels decreased during the 2-week trial by more than 50%. In conclusion,
      transforming growth factor-beta1 release and likely downregulation of its
      expression may constitute novel pharmacological effects of sulodexide.

PMID- 19117966
TI  - Comparison of immunogenic potentials of bovine thrombin preparations.
AB  - Using a membrane filtration step, bovine crude thrombin was purified into
      thrombin 4A and 4B preparations. The purpose of this study was to determine
      whether the improved purity of a bovine thrombin preparation can reduce its
      overall immunogenic potential and lower the risk of development of factor V
      antibodies. Bovine crude thrombin and its purified versions, thrombin 4A and 4B,
      were administered to individual groups of rabbits on days 0, 21, 42, 91, 123, and
      151 using standard immunologic methods. Blood was drawn from each rabbit on days
      30, 50, 105, 137, and 165, and the pooled antisera from individual groups were
      purified to obtain the Ig Gs using protein G affinity columns. Using Western
      blotting, the specificity of each immunoglobulin G collected at the first time
      point (day 30) and last time point (day 165) was determined. The results of
      Western blotting using the Ig Gs collected on days 30 and 165 were consistent;
      both demonstrating that thrombin 4B has the least immunogenic potential among the
      3 thrombin preparations tested. Compared with the immunoglobulin Gs collected on
      day 30, the Ig Gs from day 165 did not show obvious difference regarding their
      ability to detect antigens in bovine thrombin samples. Neither showed cross
      reactivity with human coagulation factors nor the recognition of bovine factor Va
      antigens. These results suggest that despite the presence of a trace amount of
      bovine factor Va antigen in bovine thrombin preparations, these contaminants
      failed to elicit the generation of antibodies against factor Va light chain in
      rabbit.

PMID- 19117967
TI  - In vivo hemostatic effect of the medicinal plant extract Ankaferd  Blood Stopper
      in rats pretreated with warfarin.
AB  - AIM: Ankaferd comprises a mixture of Thymus vulgaris, Glycyrrhiza glabra, Vitis
      vinifera, Alpinia officinarum and Urtica dioica. Ankaferd Blood Stopper (ABS) has
      been approved in the management of bleedings. This study aimed to evaluate in
      vivo hemostatic effect of ABS in rats pretreated with warfarin. MATERIALS AND
      METHODS: Wistar rats (210-270 g) were treated either with warfarin (2 mg/kg) or
      vehicle (0.9% NaCl) orally before bilateral hind leg amputation. ABS was
      administered topically to one of the amputed legs. The duration of bleeding and
      the amount of bleeding were measured to evaluate the hemostatic effect of ABS.
      RESULTS: Topical ABS administration to amputed leg shortened the duration of
      bleeding markedly in both untreated and warfarin-treated rats by 31.9% [1.42 min
      (95% CI: 0.35-2.49)] and 43.5% [5.12 min (95% CI: 2.16-8.07)] respectively. The
      amount of bleeding in ABS-administered amputed leg showed a decrease by 53.8% in
      warfarin-treated group. CONCLUSIONS: ABS has in vivo hemostatic actions that may
      provide a therapeutic potential for the management of patients with deficient
      primary hemostasis in clinical medicine.

PMID- 19117968
TI  - Venous thromboembolism in young female while on oral contraceptives: high
      frequency of inherited thrombophilia and analysis of thrombotic events in 400
      czech women.
AB  - Oral contraceptive use is a common risk factor for venous thromboembolism in
      women of reproductive age. The presence of inherited thrombophilia further
      increases this risk. METHODS: We analyzed a large group of 400 Czech women with
      venous thromboembolism in association with oral contraceptive with regard to
      duration of use at the time of manifestation of venous thromboembolism, the
      frequency of inherited and acquired thrombophilia, the frequency of eliciting
      risk factor for thrombosis including immobilization, surgery, administration of
      plaster cast, long travel, and so on, and the type of thrombosis. The mean age of
      the women was 26 years, and the average duration of use was 45 months at the
      onset of thrombosis. RESULTS: Venous thrombosis solely due to the pill occurred
      in 57% of the women, and in the other 43%, an additional transient eliciting
      factor was recognized. Among the clinical manifestation, distal thrombosis
      prevailed (N = 231, 58%) followed by proximal deep vein thrombosis (N = 65, 16%),
      pulmonary embolism (N = 21, 5%), and thrombosis in unusual sites (N = 20, 5%).
      Inherited or acquired thrombophilia was diagnosed in 195 (49%) women: factor V
      Leiden mutation in 35%, congenital deficiency of antithrombin in 1.8%, protein C
      in 0.8%, protein S in 1%, F IIG20210A in 5%, and antiphospholipid syndrome (APS)
      in 5.3%. Among the most common risk factors were immobilization of lower limb,
      minor and major surgery, and trauma. CONCLUSION: The results confirm that venous
      thromboembolism is a multifactorial disease in which thrombophilia screening is
      needed in young symptomatic women on the pill with thrombosis. The results also
      emphasize the value of proper thromboprophylaxis in women while on oral
      contraceptive in situations of increased risk for venous thromboembolism.

PMID- 19117969
TI  - Inhibition of ovulation by a lipoxygenase inhibitor involves reduced
      cyclooxygenase-2 expression and prostaglandin E2 production in gonadotropin
      primed immature rats.
AB  - Potential roles of cyclooxygenase (COX) pathway of arachidonic acid (AA)
      metabolism are established in a murine model of induced ovulation.
      Pharmacological inhibition of an alternative lipoxygenase (LOX) pathway has been
      shown to cause defective ovulation, but the mechanism is still undefined. This
      study investigated the effects of two LOX inhibitors and their time dependency on
      ovulation and COX activity in gonadotropins (eCG and human chorionic gonadotropin
      (hCG))-primed immature rats. Intra-ovarian bursal treatment with a general LOX
      inhibitor nordihydroguaiaretic acid (NDGA) at 0 h post-hCG (hCG0h) dose
      dependently inhibited ovulation rate. The drug was still but less effective when
      treated at hCG6h. A more specific inhibitor, 3,4-dihydroxyphenyl ethanol (DPE)
      was also inhibitory when treated at hCG0h but not at hCG6h. Interestingly,
      treatment with DPE at hCG0h resulted in attenuated expression of immunoreactive
      PTGS2 in granulosa layers and concomitant decrease in ovarian prostaglandin E(2)
      (PGE(2)) content at hCG8h. NDGA treatment reduced immunoreactive PTGS2. Ovulatory
      impairment by both inhibitors was prevented by systemic administration of PGE(2)
      at hCG6h. Immunohistochemistry revealed the expression of ALOX5 and ALOX12 in
      both thecal and granulosa layers of preovulatory follicles and, notably, the
      augmented immunoreactivities during 8 h after hCG treatment. Our results indicate
      the probable presence of multiple LOX isoforms and that specific inhibition of
      LOX at an early stage of hCG-signaling led to reduced PTGS2 activity and thus
      defective ovulation. They reveal a probable relationship between two pathways of
      AA metabolism and account at least partly for the mechanism by which the LOX
      inhibitor causes impaired ovulation.

PMID- 19117970
TI  - Hepatic rosai-dorfman disease with coincidental lymphoma: report of a case.
AB  - Rosai-Dorfman disease (RDD; sinus histiocytosis with massive lymphoadenopathy) is
      a rare, usually nodal self-limited disease. Sometimes nodal disease is coupled
      with extranodal localizations, in which case the disease can follow a protracted
      clinical course characterized by remissions and relapses and, exceptionally, a
      fatal outcome. Exclusive extranodal localizations are rare and their prognosis
      variable. This study reports a case of RDD apparently limited to the liver
      coexisting with a diffuse (stage IV) relapsing follicular lymphoma. The patient
      is alive and well 24 months after the diagnosis of the lymphoma. It is
      conceivable that the lymphoma has induced RDD via an immunological disorder,
      possibly involving interleukin expression. The favorable outcome supports the
      belief that the prognosis of RDD is largely dependent on the number of extranodal
      sites involved, rather than on the specific sites themselves.

PMID- 19117971
TI  - Images in pathology. Mixed tumour of the skin with extensive ossification and
      bone marrow formation on the scalp of a young patient.

PMID- 19117972
TI  - Images in pathology. Multifocal sclerosing thyroiditis.

PMID- 19117973
TI  - The histological features of intestinal spirochetosis in a series of 113
      patients.
AB  - A multicenter retrospective review of cases diagnosed as spirochetosis was
      performed to determine the presenting symptoms and histological changes. A total
      of 113 cases were retrieved from the archives, consisting of 97 colorectal
      specimens and 16 appendices. In only 25 cases was the presenting symptom recorded
      as diarrhea. Of the colorectal specimens, 87 (90%) showed no mucosal abnormality
      (apart from the spirochetes); the other 10 showed mucosal inflammation but 6 of
      them had a diagnosis of another inflammatory disease process accounting for the
      inflammatory changes. Five appendices showed acute appendicitis; the other 11
      were unremarkable. It is concluded that spirochetosis in an unselected general
      population is unlikely to be of pathological significance. Furthermore, if
      spirochetosis is observed in an inflamed biopsy, it is most likely to be an
      incidental finding.

PMID- 19117974
TI  - Diffusely infiltrating endometrial carcinomas with no stromal response: report of
      a series, including cases with cervical and ovarian involvement and emphasis on
      the potential for misdiagnosis.
AB  - Endometrial carcinomas, particularly of endometrioid type, can invade the
      myometrium or cervix without eliciting a stromal desmoplastic or inflammatory
      response and have been referred to as diffusely infiltrating endometrial
      carcinomas. This study describes a series of 14 endometrial carcinomas
      infiltrating as single "naked" glands without a stromal response. The neoplasms
      consisted of 12 endometrioid carcinomas, 1 mixed endometrioid and clear cell
      carcinoma, and 1 serous carcinoma. In all cases, there was myometrial invasion
      without stromal response. Seven cases exhibited cervical stromal involvement and
      in 2 there was involvement of both ovaries in a similar pattern. Several of the
      cases were seen in consultation and the pattern of infiltration raised a number
      of differential diagnoses, both benign and malignant, depending on the site of
      tumor involvement, including adenomyosis, adenomyoma, primary endocervical
      glandular lesions, cervical mesonephric remnants, endometriosis or
      tuboendometrioid metaplasia, and ovarian cortical inclusion cysts. Although this
      pattern of invasion has been reported previously, it continues to present
      diagnostic difficulties.

PMID- 19117975
TI  - Simultaneous occurrence of IgG4-related chronic sclerosing dacryoadenitis and
      chronic sclerosing sialadenitis associated with lymph node involvement and
      Warthin's tumor.
AB  - Chronic sclerosing dacryoadenitis and chronic sclerosing sialadenitis have been
      shown to belong to the group of diseases referred to as IgG4-related sclerosing
      disease. The authors report a case of the simultaneous occurrence of IgG4-related
      sclerosing disease in both lacrimal and submandibular glands, clinically
      simulating malignant lymphoma. A cervical lymph node and a Warthin's tumor were
      also involved. This unique case of multiple organ involvement in IgG4-related
      sclerosing disease is documented.

PMID- 19117976
TI  - Treatment in an outpatient setting for a patient with an infected, surgical wound
      with hypergranulation tissue.
AB  - The purpose of this article is to describe a multifaceted approach to wound care
      in an outpatient setting for a patient with an infected, nonhealing surgical
      wound with hypergranulation tissue following fasciotomy for acute compartment
      syndrome. A 44-year-old male underwent an anterior and lateral lower extremity
      compartment fasciotomy and developed a persistent right anterolateral lower leg
      wound. Thirty-six days after fasciotomy he came to the authors' clinic after 2
      failed skin grafts with an infected wound covered in hypergranulation tissue.
      Treatment included sharp debridement, saline irrigation, patient education, and
      dressing changes during 9 treatment sessions. The patient's total wound surface
      area decreased from 5.2 cm x 17.3 cm to 4 cm x 15 cm with increased
      epithelialization from approximately 40% to 85% after 29 days of treatment. This
      article demonstrates the positive effect of a multifaceted approach for
      facilitation of wound healing in a lower extremity wound following fasciotomy.

PMID- 19117977
TI  - Novel hands-free pointer improves instruction efficiency in laparoscopic surgery.
AB  - To improve instruction efficiency during advanced laparoscopic surgery, a hands
      free, head-controlled, multimonitor pointer was developed. One instructor guided
      20 trainees to locate critical points on a simulated laparoscopic cholecystectomy
      model. Twenty points, visible to the instructor only, were selected on a photo of
      a partially dissected gallbladder placed within a laparoscopic trainer box. For
      each trainee, the points were randomized to 2 groups of 10 points with the
      instructor providing verbal guidance only or guidance assisted by the head
      controlled pointer that appeared on both the instructor's and trainees' monitors.
      The primary outcome was the time to locate 10 points. Total time was shorter with
      the pointer than with verbal guidance alone (65 +/- 14 vs 119 +/- 34 seconds, P <
      .001). The average of mean individual times to locate each point was shorter with
      the pointer than without (5.4 +/- 0.5 vs 11.9 +/- 2.4 seconds, P < .001). The
      instructor's efficiency improved over time with both verbal guidance (P = .007)
      and with the pointer (P = .001). The benefit of pointer instruction was greater
      in trainees with laparoscopic experience compared with those without experience
      (P = .006). Use of a hands-free pointer improved instruction efficiency in
      simulated laparoscopy. Experienced surgeons benefited the most.

PMID- 19117978
TI  - The year ahead.

PMID- 19117979
TI  - Macrophage inhibitory cytokine-1: possible bridge molecule of inflammation and
      prostate cancer.
AB  - There is emerging evidence that inflammation may lead to prostate cancer
      development. Although inflammation is an essential response to injury or
      infection, chronic inflammation is harmful and causes tissue damage. Increasing
      evidence suggests that inflammation leads to the development of epithelial
      cancers; however, studies on inflammation-targeted genes that might contribute to
      the development of cancer are at the beginning stage. Here, we describe
      macrophage inhibitory cytokine-1, which provides a potential link between
      inflammation and prostate cancer. Understanding the regulation of macrophage
      inhibitory cytokine-1 in response to inflammation may have potential for novel
      therapeutic strategies.

PMID- 19117980
TI  - Adenoviral E1A function through Myc.
AB  - The study of DNA tumor viruses has been invaluable in uncovering the cellular
      nodes and pathways that contribute to oncogenesis. Perhaps one of the best
      studied oncoproteins encoded by a DNA tumor virus is adenovirus E1A, which
      modifies the function of key regulatory proteins such as retinoblastoma (Rb) and
      the chromatin remodeling protein p400. Although the interaction of E1A with Rb
      has long been known to target regulation of the E2F transcription factors, the
      downstream target of the E1A-p400 interaction has remained elusive. We have
      recently reported that a critical downstream link of the E1A-p400 nexus is the
      oncoprotein transcription factor c-Myc. Through its interaction with p400, E1A
      stabilizes Myc and promotes formation of Myc-p400 complexes on chromatin, leading
      to activation of Myc target genes. These findings point to an important role for
      p400 in Myc function and reveal that E1A drives oncogenesis by tapping into two
      important transcriptional networks: those of E2F and Myc.

PMID- 19117981
TI  - Sequence variants at 22q13 are associated with prostate cancer risk.
AB  - To search for genetic variants that are associated with prostate cancer risk in
      the genome, we combined the data from our genome-wide association study (GWAS) in
      a population-based case-control study in Sweden with publicly available GWAS data
      from the Cancer Genetic Markers of Susceptibility (CGEMS) study. We limited the
      cases to those with aggressive disease in an attempt to identify risk variants
      that are associated with this most clinically relevant form of the disease. Among
      the most likely candidate single nucleotide polymorphisms (SNP) identified from
      the two GWAS, we sequentially confirmed one SNP at 22q13 in two independent study
      populations: the remaining subjects in Cancer of the Prostate in Sweden and a
      hospital-based case-control study at Johns Hopkins Hospital. Association of
      aggressive prostate cancer with the SNP at 22q13 was also observed in the
      publicly available data of four additional study populations from the second
      stage of the CGEMS study. In all seven study populations examined, the frequency
      of allele "C" of rs9623117 at 22q13 was consistently higher in aggressive cases
      than in controls. The combined allelic test was highly significant, with P = 5.0
      x 10(-7). The odds ratio (OR) of allele C for aggressive prostate cancer was
      estimated to be 1.18 [95% confidence interval (95% CI), 1.11-1.26]. However, the
      SNP was also associated with nonaggressive prostate cancer, with an estimated OR
      of 1.11 (95% CI, 1.04-1.19; P = 0.004). The risk-associated variants are located
      within the genomic region of TNRC6B, a gene involved in miRNA-mediated mRNA
      degradation. Additional studies are warranted to further confirm the association.

PMID- 19117982
TI  - Ligand-independent androgen receptor variants derived from splicing of cryptic
      exons signify hormone-refractory prostate cancer.
AB  - Suppression of androgen production and function provides palliation but not cure
      in men with prostate cancer (PCa). Therapeutic failure and progression to hormone
      refractory PCa (HRPC) are often accompanied by molecular alterations involving
      the androgen receptor (AR). In this study, we report novel forms of AR alteration
      that are prevalent in HRPC. Through in silico sequence analysis and subsequent
      experimental validation studies, we uncovered seven AR variant transcripts
      lacking the reading frames for the ligand-binding domain due to splicing of
      "intronic" cryptic exons to the upstream exons encoding the AR DNA-binding
      domain. We focused on the two most abundantly expressed variants, AR-V1 and AR
      V7, for more detailed analysis. AR-V1 and AR-V7 mRNA showed an average 20-fold
      higher expression in HRPC (n = 25) when compared with hormone-naive PCa (n = 82;
      P < 0.0001). Among the hormone-naive PCa, higher expression of AR-V7 predicted
      biochemical recurrence following surgical treatment (P = 0.012). Polyclonal
      antibodies specific to AR-V7 detected the AR-V7 protein frequently in HRPC
      specimens but rarely in hormone-naive PCa specimens. AR-V7 was localized in the
      nuclei of cultured PCa cells under androgen-depleted conditions, and
      constitutively active in driving the expression of canonical androgen-responsive
      genes, as revealed by both AR reporter assays and expression microarray analysis.
      These results suggest a novel mechanism for the development of HRPC that warrants
      further investigation. In addition, as expression markers for lethal PCa, these
      novel AR variants may be explored as potential biomarkers and therapeutic targets
      for advanced PCa.

PMID- 19117983
TI  - GEMS (Gene Expression MetaSignatures), a Web resource for querying meta-analysis
      of expression microarray datasets: 17beta-estradiol in MCF-7 cells.
AB  - With large amounts of public expression microrray data being generated by
      multiple laboratories, it is a significant task for the bench researcher to
      routinely identify available datasets, and then to evaluate the collective
      evidence across these datasets for regulation of a specific gene in a given
      system. 17beta-Estradiol stimulation of MCF-7 cells is a widely used model in the
      growth of breast cancer. Although myriad independent studies have profiled the
      global effects of this hormone on gene expression in these cells, disparate
      experimental variables and the limited power of the individual studies have
      combined to restrict the agreement between them as to the specific gene
      expression signature elicited by this hormone. To address these issues, we have
      developed a freely accessible Web resource, Gene Expression MetaSignatures (GEMS)
      that provides the user a consensus for each gene in the system. We conducted a
      weighted meta-analysis encompassing over 13,000 genes across 10 independent
      published datasets addressing the effect of 17beta-estradiol on MCF-7 cells at
      early (3-4 hours) and late (24 hours) time points. In a literature survey of 58
      genes previously shown to be regulated by 17beta-estradiol in MCF-7 cells, the
      meta-analysis combined the statistical power of the underlying datasets to call
      regulation of these genes with nearly 85% accuracy (false discovery rate
      corrected P < 0.05). We anticipate that with future expression microarray dataset
      contributions from investigators, GEMS will evolve into an important resource for
      the cancer and nuclear receptor signaling communities.

PMID- 19117984
TI  - Functional interaction between BubR1 and securin in an anaphase-promoting
      complex/cyclosomeCdc20-independent manner.
AB  - Activation of the mitotic checkpoint requires the precise timing and spatial
      organization of mitotic regulatory events, and ensures accurate chromosome
      segregation. Mitotic checkpoint proteins such as BubR1 and Mad2 bind to Cdc20,
      and inhibit anaphase-promoting complex/cyclosome(Cdc20)-mediated securin
      degradation and the onset of anaphase. BubR1 mediates the proper attachment of
      microtubules to kinetochores, and links the regulation of chromosome-spindle
      attachment to mitotic checkpoint signaling. Therefore, disruption of BubR1
      activity results in a loss of the checkpoint control, chromosome instability,
      and/or early onset of malignancy. In this study, we show that BubR1 directly
      interacts with securin in vitro and in vivo. In addition, the BubR1 interaction
      contributes to the stability of securin, and there is a significant positive
      correlation between BubR1 and securin expressions in human cancer. Importantly,
      BubR1 competes with Cdc20 for binding to securin, and thereby the interaction
      between BubR1 and securin is greatly increased by the depletion of Cdc20. Our
      findings may identify a novel regulation of BubR1 that can generate an additional
      anaphase-inhibitory signal through the Cdc20-independent interaction of BubR1
      with securin.

PMID- 19117985
TI  - TGFBI deficiency predisposes mice to spontaneous tumor development.
AB  - Loss of TGFBI, a secreted protein induced by transforming growth factor-beta, has
      been implicated in cell proliferation, tumor progression, and angiogenesis by in
      vitro studies. However, in vivo antitumor functions of TGFBI as well as the
      underlying molecular mechanism are not well understood. To these aims, we have
      generated a mouse model with disruption of TGFBI genomic locus. Mice lacking
      TGFBI show a retarded growth and are prone to spontaneous tumors and 7,12
      dimethylbenz(a)anthracene-induced skin tumors. In relation to wild-type (WT)
      mouse embryonic fibroblasts (MEF), TGFBI(-/-) MEFs display increased frequencies
      of chromosomal aberration and micronuclei formation and exhibit an enhanced
      proliferation and early S-phase entry. Cyclin D1 is up-regulated in TGFBI(-/-)
      MEFs, which correlates with aberrant activation of transcription factor cyclic
      AMP-responsive element binding protein (CREB) identified by chromatin
      immunoprecipitation and luciferase reporter assays. TGFBI reconstitution in
      TGFBI(-/-) cells by either retroviral infection with WT TGFBI gene or supplement
      with recombinant mouse TGFBI protein in the culture medium leads to the
      suppression of CREB activation and cyclin D1 expression, and further inhibition
      of cell proliferation. Cyclin D1 up-regulation was also identified in most of the
      tumors arising from TGFBI(-/-) mice. Our studies provide the first evidence that
      TGFBI functions as a tumor suppressor in vivo.

PMID- 19117987
TI  - Inhibition of DNA methyltransferase activates tumor necrosis factor alpha-induced
      monocytic differentiation in acute myeloid leukemia cells.
AB  - Transcriptional silencing via promoter methylation of genes important for cell
      growth and differentiation plays a key role in myeloid leukemogenesis. We find
      that clinically achievable levels of 5-aza-2'-deoxycytidine (5-AZA-dC), a potent
      inhibitor of DNA methylation, can modify chromatin and restore the ability of
      tumor necrosis factor alpha (TNFalpha) to induce monocytic differentiation of the
      acute myeloid leukemia cells NB4 and U937. Although 5-AZA-dC cannot fully induce
      differentiation, we show that 5-AZA-dC acts directly on TNFalpha-responsive
      promoters to facilitate TNFalpha-induced transcriptional pathways leading to
      differentiation. 5-AZA-dC regulates the expression of Dif-2, a TNFalpha target
      gene, by deacetylating chromatin domains in a methylation-dependent manner.
      Chromatin immunoprecipitation analyses of the Dif-2 promoter show histone
      hyperacetylation and a recruitment of the nuclear factor-kappaB transcription
      factor in response to 5-AZA-dC. Furthermore, 5-AZA-dC plus TNFalpha enhances the
      level of phosphorylated RNA Pol II at the Dif-2 promoter via synergistic
      recruitment of TFIIH. We conclude that nonspecific changes in chromatin can allow
      a specific transcriptional inducer to overcome blocks in leukemic cell
      differentiation. Our results support the concept of low doses of 5-AZA-dC acting
      in combination with other agents to target epigenetic changes that drive
      malignant growth in leukemic cells. [Cancer Res 2009;69(1):55-64].

PMID- 19117986
TI  - Impaired Bub1 function in vivo compromises tension-dependent checkpoint function
      leading to aneuploidy and tumorigenesis.
AB  - Bub1 is a serine/threonine kinase originally described as a core component of the
      spindle assembly checkpoint (SAC) mechanism in yeast. Bub1 binding at
      kinetochores has been reported to be required for SAC function and localization
      of other SAC components. A proper SAC is believed to be essential for murine
      embryonic development, as all previously described null mutations in SAC
      components in mice cause embryonic lethality. We produced mice harboring a Bub1
      mutant allele lacking exons 2 and 3, resulting in a hypomorphic mutant expressed
      at <5% of wild-type levels. Despite this significant reduction, homozygous mutant
      animals are viable on a mixed 129P2/B6 or FVB background but display increased
      tumorigenesis with aging, whereas mice with a C57Bl/6J background die
      perinatally. Bub1 mutant murine embryonic fibroblasts (MEFs) display defects in
      chromosome congression to the metaphase plate, severe chromosome missegregation,
      and aneuploidy accompanied by high levels of premature senescence. Mutant MEFs
      have a robust SAC in response to nocodazole treatment but an impaired response to
      Taxol. Mutant MEFs also show reduced kinetochore localization of BubR1, but not
      of Mad2. The significant reduction in SAC response to Taxol, but not nocodazole,
      coupled with the reduced binding of BubR1, but not Mad2, indicates that Bub1 is
      particularly critical for the SAC response to a lack of tension on kinetochores.
      Thus, Bub1 is essential for proper chromosome segregation, a defect that can lead
      to severe phenotypes, including perinatal lethality and a predisposition to
      cancer.

PMID- 19117989
TI  - Silencing PinX1 compromises telomere length maintenance as well as tumorigenicity
      in telomerase-positive human cancer cells.
AB  - The nucleolar protein PinX1 has been proposed to be a putative tumor suppressor
      due to its binding to and inhibition of the catalytic activity of telomerase, an
      enzyme that is highly expressed in most human cancers in which it counteracts
      telomere shortening-induced senescence to confer cancer cell immortalization.
      However, the role of PinX1 in telomere regulation, as well as in cancer, is still
      poorly understood. In this study, we showed that the PinX1 protein is
      constitutively expressed in various human cells regardless of their telomerase
      activity and malignant status. Most interestingly, we found that silencing PinX1
      expression by a potent short hairpin RNA construct led to a robust telomere
      length shortening and growth inhibition in telomerase-positive but not in
      telomerase-negative human cancer cells. We further showed that silencing PinX1
      significantly reduced the endogenous association of telomerase with the Pot1
      containing telomeric protein complex, and therefore, could account for the
      phenotypic telomere shortening in the affected telomerase-positive cancer cells.
      Our results thus reveal a novel positive role for PinX1 in telomerase/telomere
      regulations and suggest that the constitutive expression of PinX1 attributes to
      telomere maintenance by telomerase and tumorigenicity in cancer cells.

PMID- 19117988
TI  - A feed-forward loop involving protein kinase Calpha and microRNAs regulates tumor
      cell cycle.
AB  - Protein kinase Calpha (PKCalpha) has been implicated in cancer, but the mechanism
      is largely unknown. Here, we show that PKCalpha promotes head and neck squamous
      cell carcinoma (SCCHN) by a feed-forward network leading to cell cycle
      deregulation. PKCalpha inhibitors decrease proliferation in SCCHN cell lines and
      xenografted tumors. PKCalpha inhibition or depletion in tumor cells decreases DNA
      synthesis by suppressing extracellular signal-regulated kinase phosphorylation
      and cyclin E synthesis. Additionally, PKCalpha down-regulates miR-15a, a microRNA
      that directly inhibits protein synthesis of cyclin E, as well as other cell cycle
      regulators. Furthermore, both PKCalpha and cyclin E protein expression are
      increased in primary tumors, and PKCalpha inversely correlates with miR-15a
      expression in primary tumors. Finally, PKCalpha is associated with poor prognosis
      in SCCHN. These results identify PKCalpha as a key regulator of SCCHN tumor cell
      growth by a mechanism involving activation of mitogen-activated protein kinase,
      an initiator of the cell cycle, and suppression of miR-15a, an inhibitor of DNA
      synthesis. Although the specific components may be different, this type of feed
      forward loop network, consisting of a stimulus that activates a positive signal
      and removes a negative brake, is likely to be a general one that enables
      induction of DNA synthesis by a variety of growth or oncogenic stimuli.

PMID- 19117990
TI  - Distinct roles for mammalian target of rapamycin complexes in the fibroblast
      response to transforming growth factor-beta.
AB  - Transforming growth factor-beta (TGF-beta) promotes a multitude of diverse
      biological processes, including growth arrest of epithelial cells and
      proliferation of fibroblasts. Although the TGF-beta signaling pathways that
      promote inhibition of epithelial cell growth are well characterized, less is
      known about the mechanisms mediating the positive response to this growth factor.
      Given that TGF-beta has been shown to promote fibrotic diseases and desmoplasia,
      identifying the fibroblast-specific TGF-beta signaling pathways is critical.
      Here, we investigate the role of mammalian target of rapamycin (mTOR), a known
      effector of phosphatidylinositol 3-kinase (PI3K) and promoter of cell growth, in
      the fibroblast response to TGF-beta. We show that TGF-beta activates mTOR complex
      1 (mTORC1) in fibroblasts but not epithelial cells via a PI3K-Akt-TSC2-dependent
      pathway. Rapamycin, the pharmacologic inhibitor of mTOR, prevents TGF-beta
      mediated anchorage-independent growth without affecting TGF-beta transcriptional
      responses or extracellular matrix protein induction. In addition to mTORC1, we
      also examined the role of mTORC2 in TGF-beta action. mTORC2 promotes TGF-beta
      induced morphologic transformation and is required for TGF-beta-induced Akt S473
      phosphorylation but not mTORC1 activation. Interestingly, both mTOR complexes are
      necessary for TGF-beta-mediated growth in soft agar. These results define
      distinct and overlapping roles for mTORC1 and mTORC2 in the fibroblast response
      to TGF-beta and suggest that inhibitors of mTOR signaling may be useful in
      treating fibrotic processes, such as desmoplasia.

PMID- 19117991
TI  - K-ras and Wnt signaling synergize to accelerate prostate tumorigenesis in the
      mouse.
AB  - Aberrant Ras and Wnt signaling are emerging as key events in the multistep nature
      of prostate tumorigenesis and progression. Here, we report the generation of a
      compound model of prostate cancer to define the synergism of activated K-ras (K
      ras(+/V12)) and dominant stabilized beta-catenin (Catnb(+/lox(ex3))) in the
      murine prostate. Recombination of floxed alleles and subsequent expression of
      oncogenic transgenes was mediated by Cre recombinase expression governed by the
      composite Probasin (PB) promoter (termed PBCre). Concomitant with elevated
      mitogen-activated protein kinase (MAPK) signaling, PBCre(+)K-ras(+/V12) mice
      developed AH at 100 days (100% incidence) and low-grade prostate intraepithelial
      neoplasia and adenocarcinoma (60% and 7% incidence) by 500 days.
      PBCre(+)Catnb(+/lox(ex3)) mice showed reduced longevity (average 428 days) and
      were predisposed to PIN-like keratinized squamous metaplasia at 100 days (100%
      incidence) and adenocarcinoma (100% incidence) at end-point. These lesions
      displayed elevated Wnt signaling and basal levels of MAPK signaling. Synchronous
      activation of K-ras and beta-catenin significantly reduced survival (average 189
      days), reflecting accelerated tumorigenesis and the development of invasive
      carcinoma that displayed activated Wnt and MAPK signaling. Notably, expression of
      the basal cell marker p63 negatively correlated with tumor grade, resembling
      human prostate adenocarcinoma. Taken together, our data show that combinatorial
      oncogenic mutations of K-ras and beta-catenin drive rapid progression of prostate
      tumorigenesis to invasive carcinoma, characterized by the synergistic elevation
      of androgen receptor, cyclooxygenase-2, and c-Myc.

PMID- 19117992
TI  - PCPH/ENTPD5 expression confers to prostate cancer cells resistance against
      cisplatin-induced apoptosis through protein kinase Calpha-mediated Bcl-2
      stabilization.
AB  - Prostate cancer (PCa) frequently develops antiapoptotic mechanisms and acquires
      resistance to anticancer drugs. Therefore, identifying PCa drug resistance
      determinants should facilitate designing more effective chemotherapeutic
      regimens. Recently, we described that the PCPH protein becomes highly expressed
      in human prostatic intraepithelial neoplasia and in PCa, and that the functional
      interaction between PCPH and protein kinase Cdelta (PKCdelta) increases the
      invasiveness of human PCa. Here, we report that the functional interaction
      between PCPH and a different PKC isoform, PKCalpha, confers resistance against
      cisplatin-induced apoptosis to PCa cells. This interaction elicits a mechanism
      ultimately resulting in the posttranslational stabilization and subsequent
      elevated expression of Bcl-2. Stable knockdown of either PCPH, mt-PCPH, or
      PKCalpha in PCa cells decreased Ser70-phosphorylated Bcl-2 and total Bcl-2
      protein, thereby increasing their cisplatin sensitivity. Conversely, forced
      expression of the PCPH protein or, in particular, of the mt-PCPH oncoprotein
      increased the levels of phosphorylated PKCalpha concurrently with those of Ser70
      phosphorylated and total Bcl-2 protein, thus promoting cisplatin resistance.
      Consistently, Bcl-2 knockdown sensitized PCa cells to cisplatin treatment and,
      more importantly, reversed the cisplatin resistance of PCa cells expressing the
      mt-PCPH oncoprotein. Moreover, reexpression of Bcl-2 in PCPH/mt-PCPH knockdown
      PCa cells reversed the cisplatin sensitization caused by PCPH or mt-PCPH down
      regulation. These findings identify PCPH and mt-PCPH as important participants in
      the chemotherapy response of PCa cells, establish a role for PCPH-PKCalpha-Bcl-2
      functional interactions in the drug response process, and imply that targeting
      PCPH expression before, or simultaneously with, chemotherapy may improve the
      treatment outcome for PCa patients.

PMID- 19117993
TI  - BRCA1-associated protein 1 interferes with BRCA1/BARD1 RING heterodimer activity.
AB  - The breast and ovarian tumor suppressor BRCA1 constitutes a RING heterodimer E3
      ligase with BARD1. BRCA1-associated protein 1 (BAP1) is a ubiquitin COOH-terminal
      hydrolase that was initially identified as a protein that bound to the RING
      finger domain of BRCA1. However, how BAP1 contributes to the E3 activity of
      BRCA1/BARD1 is unclear. Here, we report that BAP1 interacts with BARD1 to inhibit
      the E3 ligase activity of BRCA1/BARD1. Domains comprised by residues 182-365 of
      BAP1 interact with the RING finger domain of BARD1, and surface plasmon resonance
      spectroscopy (BIAcore) analyses showed that BAP1 interferes with the BRCA1/BARD1
      association. The perturbation resulted in inhibition of BRCA1 autoubiquitination
      and NPM1/B23 ubiquitination by BRCA1/BARD1. Although BAP1 was capable of
      deubiquitinating the polyubiquitin chains mediated by BRCA1/BARD1 in vitro, a
      catalytically inactive mutant of BAP1, C91S, still inhibited the ubiquitination
      in vitro and in vivo, implicating a second mechanism of action. Importantly,
      inhibition of BAP1 expression by short hairpin RNA resulted in hypersensitivity
      of the cells to ionizing irradiation and in retardation of S-phase progression.
      Together, these results suggest that BAP1 and BRCA1/BARD1 coordinately regulate
      ubiquitination during the DNA damage response and the cell cycle.

PMID- 19117994
TI  - A new model for prediction of drug distribution in tumor and normal tissues:
      pharmacokinetics of temozolomide in glioma patients.
AB  - Difficulties in direct measurement of drug concentrations in human tissues have
      hampered the understanding of drug accumulation in tumors and normal tissues. We
      propose a new system analysis modeling approach to characterize drug distribution
      in tissues based on human positron emission tomography (PET) data. The PET system
      analysis method was applied to temozolomide, an important alkylating agent used
      in the treatment of brain tumors, as part of standard temozolomide treatment
      regimens in patients. The system analysis technique, embodied in the convolution
      integral, generated an impulse response function that, when convolved with
      temozolomide plasma concentration input functions, yielded predicted normal brain
      and brain tumor temozolomide concentration profiles for different temozolomide
      dosing regimens (75-200 mg/m(2)/d). Predicted peak concentrations of temozolomide
      ranged from 2.9 to 6.7 microg/mL in human glioma tumors and from 1.8 to 3.7
      microg/mL in normal brain, with the total drug exposure, as indicated by the
      tissue/plasma area under the curve ratio, being about 1.3 in tumor compared with
      0.9 in normal brain. The higher temozolomide exposures in brain tumor relative to
      normal brain were attributed to breakdown of the blood-brain barrier and possibly
      secondary to increased intratumoral angiogenesis. Overall, the method is
      considered a robust tool to analyze and predict tissue drug concentrations to
      help select the most rational dosing schedules.

PMID- 19117996
TI  - Amyloid precursor protein is a primary androgen target gene that promotes
      prostate cancer growth.
AB  - Androgen receptor (AR) is a critical transcription factor that regulates various
      target genes and contributes to the pathophysiology of prostate cancer hormone
      dependently. Here, we identify amyloid precursor protein (APP) as a primary
      androgen target through chromatin immunoprecipitation (ChIP) combined with genome
      tiling array analysis (ChIP-chip). ChIP-treated DNA were obtained from prostate
      cancer LNCaP cells with R1881 or vehicle treatment using AR or acetylated histone
      H3 antibodies. Ligand-dependent AR binding was further enriched by PCR
      subtraction. Using chromosome 21/22 arrays, we identified APP as one of the
      androgen-regulated genes with adjacent functional AR binding sites. APP
      expression is androgen-inducible in LNCaP cells and APP immunoreactivity was
      correlated with poor prognosis in patients with prostate cancer. Gain-of-function
      and loss-of-function studies revealed that APP promotes the tumor growth of
      prostate cancer. The present study reveals a novel APP-mediated pathway
      responsible for the androgen-dependent growth of prostate cancer. Our findings
      will indicate that APP could be a potential molecular target for the diagnosis
      and treatment of prostate cancer.

PMID- 19117995
TI  - Regulation of estrogen-dependent transcription by the LIM cofactors CLIM and RLIM
      in breast cancer.
AB  - Mammary oncogenesis is profoundly influenced by signaling pathways controlled by
      estrogen receptor alpha (ERalpha). Although it is known that ERalpha exerts its
      oncogenic effect by stimulating the proliferation of many human breast cancers
      through the activation of target genes, our knowledge of the underlying
      transcriptional mechanisms remains limited. Our published work has shown that the
      in vivo activity of LIM homeodomain transcription factors (LIM-HD) is critically
      regulated by cofactors of LIM-HD proteins (CLIM) and the ubiquitin ligase RING
      finger LIM domain-interacting protein (RLIM). Here, we identify CLIM and RLIM as
      novel ERalpha cofactors that colocalize and interact with ERalpha in primary
      human breast tumors. We show that both cofactors associate with estrogen
      responsive promoters and regulate the expression of endogenous ERalpha target
      genes in breast cancer cells. Surprisingly, our results indicate opposing
      functions of LIM cofactors for ERalpha and LIM-HDs: whereas CLIM enhances
      transcriptional activity of LIM-HDs, it inhibits transcriptional activation
      mediated by ERalpha on most target genes in vivo. In turn, the ubiquitin ligase
      RLIM inhibits transcriptional activity of LIM-HDs but enhances transcriptional
      activation of endogenous ERalpha target genes. Results from a human breast cancer
      tissue microarray of 1,335 patients revealed a highly significant correlation of
      elevated CLIM levels to ER/progesterone receptor positivity and poor
      differentiation of tumors. Combined, these results indicate that LIM cofactors
      CLIM and RLIM regulate the biological activity of ERalpha during the development
      of human breast cancer.

PMID- 19117997
TI  - Mutations in the phosphatidylinositol-3-kinase pathway predict for antitumor
      activity of the inhibitor PX-866 whereas oncogenic Ras is a dominant predictor
      for resistance.
AB  - The novel phosphatidylinositol-3-kinase (PI3K) inhibitor PX-866 was tested
      against 13 experimental human tumor xenografts derived from cell lines of various
      tissue origins. Mutant PI3K (PIK3CA) and loss of PTEN activity were sufficient,
      but not necessary, as predictors of sensitivity to the antitumor activity of the
      PI3K inhibitor PX-866 in the presence of wild-type Ras, whereas mutant oncogenic
      Ras was a dominant determinant of resistance, even in tumors with coexisting
      mutations in PIK3CA. The level of activation of PI3K signaling measured by tumor
      phosphorylated Ser(473)-Akt was insufficient to predict in vivo antitumor
      response to PX-866. Reverse-phase protein array revealed that the Ras-dependent
      downstream targets c-Myc and cyclin B were elevated in cell lines resistant to PX
      866 in vivo. Studies using an H-Ras construct to constitutively and
      preferentially activate the three best-defined downstream targets of Ras, i.e.,
      Raf, RalGDS, and PI3K, showed that mutant Ras mediates resistance through its
      ability to use multiple pathways for tumorigenesis. The identification of Ras and
      downstream signaling pathways driving resistance to PI3K inhibition might serve
      as an important guide for patient selection as inhibitors enter clinical trials
      and for the development of rational combinations with other molecularly targeted
      agents.

PMID- 19117999
TI  - The mechanisms of differential sensitivity to an insulin-like growth factor-1
      receptor inhibitor (BMS-536924) and rationale for combining with EGFR/HER2
      inhibitors.
AB  - Overexpression and enhanced activity of insulin-like growth factor-I receptor
      (IGF-IR) in diverse tumor types make it an attractive target for cancer therapy.
      BMS-536924 is a potent small molecule inhibitor of IGF-IR, which shows antitumor
      activity in multiple tumor models, including sarcoma. To facilitate the
      development of IGF-IR inhibitors as cancer therapy, identification of biomarkers
      for selecting patients most likely to derive clinical benefit is needed. To do
      so, 28 sarcoma and neuroblastoma cell lines were screened for in vitro response
      to BMS-536924 to identify sensitive and resistant cell lines. Notably, Ewing's
      sarcoma, rhabdomyosarcoma, and neuroblastoma are more responsive to BMS-536924,
      suggesting these specific subtypes may represent potential targeted patient
      subpopulations for the IGF-IR inhibitor. Gene expression and protein profiling
      were performed on these cell lines, and candidate biomarkers correlating with
      intrinsic and/or acquired resistance to BMS-536924 were identified. IGF-I, IGF
      II, and IGF-IR were highly expressed in sensitive cell lines, whereas IGFBP-3 and
      IGFBP-6 were highly expressed in resistant lines. Overexpression of epidermal
      growth factor receptor (EGFR) and its ligands in resistant cell lines may
      represent one possible resistance mechanism by the adaptation of IGF-IR
      independent growth using alternative signaling pathways. Based on cross-talk
      between IGF-IR and EGFR pathways, combination studies to target both pathways
      were performed, and enhanced inhibitory activities were observed. These results
      provide a strategy for testing combinations of IGF-IR inhibitors with other
      targeted therapies in clinical studies to achieve improved patient outcomes.
      Further exploration of mechanisms for intrinsic and acquired drug resistance by
      these preclinical studies may lead to more rationally designed drugs that target
      multiple pathways for enhanced antitumor efficacy.

PMID- 19117998
TI  - Aberrant activation of androgen receptor in a new neuropeptide-autocrine model of
      androgen-insensitive prostate cancer.
AB  - Treatment of advanced prostate cancer with androgen deprivation therapy
      inevitably renders the tumors castration-resistant and incurable. Under these
      conditions, neuroendocrine differentiation of prostate cancer (CaP) cells is
      often detected and neuropeptides released by these cells may facilitate the
      development of androgen independence. Exemplified by gastrin-releasing peptide
      (GRP), these neuropeptides transmit their signals through G protein-coupled
      receptors, which are often overexpressed in prostate cancer, and aberrantly
      activate androgen receptor (AR) in the absence of androgen. We developed an
      autocrine neuropeptide model by overexpressing GRP in LNCaP cells and the
      resultant cell line, LNCaP-GRP, exhibited androgen-independent growth with
      enhanced motility in vitro. When orthotopically implanted in castrated nude mice,
      LNCaP-GRP produced aggressive tumors, which express GRP, prostate-specific
      antigen, and nuclear-localized AR. Chromatin immunoprecipitation studies of LNCaP
      GRP clones suggest that GRP activates and recruits AR to the cognate promoter in
      the absence of androgen. A Src family kinase (SFK) inhibitor, AZD0530, inhibits
      androgen-independent growth and migration of the GRP-expressing cell lines, and
      blocks the nuclear translocation of AR, indicating the involvement of SFK in the
      aberrant activation of AR and demonstrating the potential use of SFK inhibitor in
      the treatment of castration-resistant CaP. In vivo studies have shown that
      AZD0530 profoundly inhibits tumor metastasis in severe combined immunodeficient
      mice implanted with GRP-autocrine LNCaP cells. This xenograft model shows
      autocrine, neuropeptide- and Src kinase-mediated progression of androgen
      independent CaP postcastration, and is potentially useful for testing novel
      therapeutic agents.

PMID- 19118000
TI  - Indibulin, a novel microtubule inhibitor, discriminates between mature neuronal
      and nonneuronal tubulin.
AB  - Microtubule inhibitors interfere with microtubule dynamics, causing cell cycle
      arrest and apoptosis. These effects are responsible for the chemotherapeutic
      activities of members of the taxane and Vinca alkaloid families in oncology.
      Unfortunately, a major side effect of the taxanes and Vinca alkaloids is the
      development of peripheral neuropathies. Indibulin (N-[pyridin-4-yl]-[1-(4
      chlorbenzyl)-indol-3-yl]-glyoxyl-amid; D-24851; ZIO-301), a novel synthetic small
      molecule microtubule inhibitor, destabilizes microtubules and has antitumor
      activity but does not exhibit neurotoxicity in preclinical animal studies. In the
      present study, it has been found that indibulin is able to discriminate between
      highly posttranslationally modified tubulin present in mature neuronal
      microtubules, and less-modified tubulin present in immature neuronal or
      nonneuronal microtubules. Vincristine and colchicine act on either tubulin
      equally well. The binding site of indibulin on mature neuronal microtubules seems
      to be inaccessible due to the posttranslational modifications, a theory that is
      supported by the observation that indibulin did not disrupt the integrity of
      highly modified microtubules present in neurites of pheochromocytoma (PC12)
      cells. The specificity of indibulin for unmodified microtubules seems to be
      dependent on the pyridyl moiety of indibulin because derivatives that have the
      pyridyl moiety replaced are not able to discriminate between highly and less
      modified tubulins. The observed broad antitumor activity of indibulin and the
      lack of central and peripheral nervous system toxicity in preclinical studies
      make it a promising candidate for development as a cancer treatment. Indibulin is
      currently in phase I clinical trials.

PMID- 19118001
TI  - Human multidrug resistance protein 7 (ABCC10) is a resistance factor for
      nucleoside analogues and epothilone B.
AB  - Multidrug resistance protein 7 (MRP7; ABCC10) is an ATP-binding cassette
      transporter which is able to transport amphipathic anions and confer resistance
      to docetaxel and, to a lesser extent, vincristine and paclitaxel. Whereas some
      detail on the resistance profile of MRP7 is known, the activities of the pump
      have not been completely determined. Here, it is shown by the analysis of MRP7
      transfected HEK293 cells that, in addition to natural product agents, MRP7 is
      also able to confer resistance to nucleoside-based agents, such as the anticancer
      agents cytarabine (Ara-C) and gemcitabine, and the antiviral agents 2',3'
      dideoxycytidine and PMEA. Consistent with the operation of an efflux pump,
      expression of MRP7 reduced the accumulation of Ara-C and PMEA. In addition, MRP7
      is also able to confer resistance to the microtubule-stabilizing agent epothilone
      B. Ectopic expression of MRP7 in mouse embryo fibroblasts deficient in P
      glycoprotein and Mrp1 revealed that MRP7 has a broad resistance profile for
      natural product agents. In this drug-sensitive cellular background, MRP7
      conferred high levels of resistance to docetaxel (46-fold), paclitaxel (116
      fold), SN-38 (65-fold), daunorubicin (7.5-fold), etoposide (11-fold), and
      vincristine (56-fold). Buthionine sulfoximine did not attenuate MRP7-conferred
      resistance to docetaxel or Ara-C. These experiments indicate that the resistance
      capabilities of MRP7 include nucleoside-based agents and a range of natural
      product anticancer agents that includes nontaxane antimicrotubule agents that are
      not susceptible to P-glycoprotein-mediated transport and that, unlike MRP1 and
      MRP2, MRP7-mediated drug transport does not involve glutathione.

PMID- 19118002
TI  - Pretargeted radioimmunotherapy using anti-CD45 monoclonal antibodies to deliver
      radiation to murine hematolymphoid tissues and human myeloid leukemia.
AB  - Radioimmunotherapy (RIT) for treatment of hematologic malignancies frequently
      fails because of disease recurrence. We therefore conducted pretargeted (P)RIT
      studies to augment the efficacy in mice of therapy using a pretargeted anti-human
      (h)CD45 antibody (Ab)-streptavidin (SA) conjugate followed by a biotinylated
      clearing agent and radiolabeled 1,4,7,10-tetraazacylodode cane N,N',N",N'''
      tetraacetic (DOTA)-biotin. Tumor-to-blood ratios at 24 hours were 20:1 using
      pretargeted anti-hCD45 RIT and <1:1 with conventional RIT. In vivo imaging
      studies confirmed that the PRIT approach provided high-contrast tumor images with
      minimal blood-pool activity, whereas directly labeled anti-hCD45 Ab produced
      distinct tumor images but the blood pool retained a large amount of labeled Ab
      for a prolonged time. Therapy experiments showed that (90)Y-DOTA-biotin
      significantly prolonged survival of mice treated with pretargeted anti-hCD45 Ab
      SA compared with mice treated with conventional RIT using (90)Y-labeled anti
      hCD45 Ab at 200 muCi. Because human CD45 antigens are confined to xenograft tumor
      cells in this model, and all murine tissues are devoid of hCD45 and will not bind
      anti-hCD45 Ab, we also compared one-step and PRIT using an anti-murine (m)CD45 Ab
      where the target antigen is present on normal hematopoietic tissues. After 24 h,
      27.3% +/- 2.8% of the injected dose of activity was delivered per gram (% ID/g)
      of lymph node using (131)I-A20-Ab compared with 40.0 +/- 5.4% ID/g for
      pretargeted (111)In-DOTA-biotin. These data suggest that pretargeted methods for
      delivering RIT may be superior to conventional RIT when targeting CD45 for the
      treatment of leukemia and may allow for the intensification of therapy, while
      minimizing toxicities.

PMID- 19118003
TI  - Cryptotanshinone inhibits constitutive signal transducer and activator of
      transcription 3 function through blocking the dimerization in DU145 prostate
      cancer cells.
AB  - Because signal transducer and activator of transcription 3 (STAT3) is
      constitutively activated in most human solid tumors and is involved in the
      proliferation, angiogenesis, immune evasion, and antiapoptosis of cancer cells,
      researchers have focused on STAT3 as a target for cancer therapy. We screened for
      natural compounds that inhibit the activity of STAT3 using a dual-luciferase
      assay. Cryptotanshinone was identified as a potent STAT3 inhibitor.
      Cryptotanshinone rapidly inhibited STAT3 Tyr705 phosphorylation in DU145 prostate
      cancer cells and the growth of the cells through 96 hours of the treatment.
      Inhibition of STAT3 Tyr705 phosphorylation in DU145 cells decreased the
      expression of STAT3 downstream target proteins such as cyclin D1, survivin, and
      Bcl-xL. To investigate the cryptotanshinone inhibitory mechanism in DU145 cells,
      we analyzed proteins upstream of STAT3. Although phosphorylation of Janus
      activated kinase (JAK) 2 was inhibited by 7 micromol/L cryptotanshinone at 24
      hours, inhibition of STAT3 Tyr705 phosphorylation occurred within 30 minutes and
      the activity of the other proteins was not affected. These results suggest that
      inhibition of STAT3 phosphorylation is caused by a JAK2-independent mechanism,
      with suppression of JAK2 phosphorylation as a secondary effect of
      cryptotanshinone treatment. Continuing experiments revealed the possibility that
      cryptotanshinone might directly bind to STAT3 molecules. Cryptotanshinone was
      colocalized with STAT3 molecules in the cytoplasm and inhibited the formation of
      STAT3 dimers. Computational modeling showed that cryptotanshinone could bind to
      the SH2 domain of STAT3. These results suggest that cryptotanshinone is a potent
      anticancer agent targeting the activation STAT3 protein. It is the first report
      that cryptotanshinone has antitumor activity through the inhibition of STAT3.

PMID- 19118004
TI  - Identification of an indispensable role for tyrosine kinase 2 in CTL-mediated
      tumor surveillance.
AB  - We showed previously that Tyk2(-/-) natural killer cells lack the ability to lyse
      leukemic cells. As a consequence, the animals are leukemia prone. Here, we show
      that the impaired tumor surveillance extends to T cells. Challenging Tyk2(-/-)
      mice with EL4 thymoma significantly decreased disease latency. The crucial role
      of Tyk2 for CTL function was further characterized using the ovalbumin-expressing
      EG7 cells. Tyk2(-/-) OT-1 mice developed EG7-induced tumors significantly faster
      compared with wild-type (wt) controls. In vivo assays confirmed the defect in
      CD8(+) cytotoxicity on Tyk2 deficiency and clearly linked it to type I IFN
      signaling. An impaired CTL activity was only observed in IFNAR1(-/-) animals but
      not on IFNgamma or IL12p35 deficiency. Accordingly, EG7-induced tumors grew
      faster in IFNAR1(-/-) and Tyk2(-/-) but not in IFNgamma(-/-) or IL12p35(-/-)
      mice. Adoptive transfer experiments defined a key role of Tyk2 in CTL-mediated
      tumor surveillance. In contrast to wt OT-1 cells, Tyk2(-/-) OT-1 T cells were
      incapable of controlling EG7-induced tumor growth.

PMID- 19118005
TI  - Genetic regulation of the response to Her-2 DNA vaccination in human Her-2
      transgenic mice.
AB  - Genetic regulation of immune reactivity to Her-2 vaccination and the consequent
      antitumor effect was tested in human Her-2 transgenic (Tg) mice of C57BL/6 (B6),
      BALB/c (BALB), and (B6x BALB) F1 (F1) background. Mice were electrovaccinated
      with Her-2 DNA with or without pretreatment with CD25 monoclonal antibody to
      remove CD25(hi) regulatory T cells. When CD25(+) T cells were intact, BALB Her-2
      Tg mice were more responsive than the other two strains in both humoral and
      cellular immunities, and their tumor growth was significantly delayed. B6 Her-2
      Tg mice responded poorly and F1 mice showed modest immune reactivity, but tumor
      growth did not change in either strain. Depletion of CD25(hi) T cells before
      vaccination significantly improved protection from tumor challenge in F1 Her-2 Tg
      mice. This was associated with elevated levels of Her-2 IgG1, IgG2a, and IgG2c
      antibodies, and some mice also showed IFN-gamma producing T-cell response. The
      same treatment induced modest improvement in B6 Her-2 Tg mice. In BALB Her-2 Tg
      mice, however, depletion of CD25(hi) T cells did not further improve antitumor
      efficacy. Although their Her-2-specific IgG1 and interleukin-5-secreting T cells
      increased, the levels of IgG2a and IFN-gamma-secreting T cells did not change.
      These results are the first to show genetic regulation of the response to a
      cancer vaccine and an unequal effect of removing CD25(hi) T cells on antitumor
      immunity. These results warrant individualized treatment plans for patients with
      heterogeneous genetic backgrounds and possibly differential intrinsic immune
      reactivity to tumor antigens.

PMID- 19118006
TI  - Tumor protein 53-induced nuclear protein 1 is a major mediator of p53 antioxidant
      function.
AB  - p53 exerts its tumor suppressor function mainly through transcriptional induction
      of target genes involved in several processes, including cell cycle checkpoints,
      apoptosis, and regulation of cell redox status. p53 antioxidant function is
      dependent on its transcriptional activity and proceeds by sequential induction of
      antioxidant and proapoptotic targets. However, none of the thus far renowned p53
      targets have proved able to abolish on their own the intracellular reactive
      oxygen species (ROS) accumulation caused by p53 deficiency, therefore pointing to
      the existence of other prominent and yet unknown p53 antioxidant targets. Here,
      we show that TP53INP1 represents such a target. Indeed, TP53INP1 transcript
      induction on oxidative stress is strictly dependent on p53. Mouse embryonic
      fibroblasts (MEF) and splenocytes derived from TP53INP1-deficient (inp1(-/-))
      mice accumulate intracellular ROS, whereas overexpression of TP53INP1 in p53
      deficient MEFs rescues ROS levels to those of p53-proficient cells, indicating
      that TP53INP1 antioxidant function is p53 independent. Furthermore, accumulation
      of ROS in inp1(-/-) cells on oxidant challenge is associated with decreased
      expression of p53 targets p21/Cdkn1a, Sesn2, TAp73, Puma, and Bax. Mutation of
      p53 Ser(58) (equivalent to human p53 Ser(46)) abrogates transcription of these
      genes, indicating that TP53INP1-mediated p53 Ser(58) phosphorylation is
      implicated in this process. In addition, TP53INP1 deficiency results in an
      antioxidant (N-acetylcysteine)-sensitive acceleration of cell proliferation.
      Finally, TP53INP1 deficiency increases oxidative stress-related lymphoma
      incidence and decreases survival of p53(+/-) mice. In conclusion, our data show
      that TP53INP1 is a major actor of p53-driven oxidative stress response that
      possesses both a p53-independent intracellular ROS regulatory function and a p53
      dependent transcription regulatory function.

PMID- 19118007
TI  - Epigenetic profiles distinguish pleural mesothelioma from normal pleura and
      predict lung asbestos burden and clinical outcome.
AB  - Mechanisms of action of nonmutagenic carcinogens such as asbestos remain poorly
      characterized. As pleural mesothelioma is known to have limited numbers of
      genetic mutations, we aimed to characterize the relationships among gene-locus
      specific methylation alterations, disease status, asbestos burden, and survival
      in this rapidly fatal asbestos-associated tumor. Methylation of 1505 CpG loci
      associated with 803 cancer-related genes were studied in 158 pleural
      mesotheliomas and 18 normal pleura. After false-discovery rate correction, 969
      CpG loci were independently associated with disease status (Q < 0.05).
      Classifying samples based on CpG methylation profile with a mixture model
      approach, methylation classes discriminated tumor from normal pleura (permutation
      P < 0.0001). In a random forests classification, the overall misclassification
      error rate was 3.4%, with <1% (n = 1) of tumors misclassified as normal (P <
      0.0001). Among tumors, methylation class membership was significantly associated
      with lung tissue asbestos body burden (P < 0.03), and significantly predicted
      survival (likelihood ratio P < 0.01). Consistent with prior work, asbestos burden
      was associated with an increased risk of death (hazard ratio, 1.4; 95% confidence
      interval, 1.1-1.8). Our results have shown that methylation profiles powerfully
      differentiate diseased pleura from nontumor pleura and that asbestos burden and
      methylation profiles are independent predictors of mesothelioma patient survival.
      We have added to the growing body of evidence that cellular epigenetic
      dysregulation is a critical mode of action for asbestos in the induction of
      pleural mesothelioma. Importantly, these findings hold great promise for using
      epigenetic profiling in the diagnosis and prognosis of human cancers.

PMID- 19118008
TI  - NORE1B is a putative tumor suppressor in hepatocarcinogenesis and may act via
      RASSF1A.
AB  - Recently, we found epigenetic silencing of the Ras effector genes NORE1B and/or
      RASSF1A in 97% of the hepatocellular carcinoma (HCC) investigated. This is strong
      evidence that the two genes are of major significance in hepatocarcinogenesis.
      Although RASSF1A serves as a tumor suppressor gene, the functions of NORE1B are
      largely unknown. Here, we studied the role of NORE1B for growth and
      transformation of cells. To understand the molecular mechanisms of action of the
      gene, we used the wild-type form and deletion mutants without the NH(2) terminus
      and CENTRAL domain, the Ras association (RA) domain, or the COOH-terminal SARAH
      domain. Intact RA and SARAH-domains were found to be necessary for NORE1B (a) to
      increase the G(0)-G(1) fraction in hepatoma cells, (b) to suppress c-Myc/Ha-Ras
      induced cell transformation, and (c) to interact closely with RASSF1A, as
      determined with fluorescence resonance energy transfer. In further studies, cell
      cycle delay by NORE1B was equally effective in hepatocyte cell lines with wild
      type or mutant Ras suggesting that NORE1B does not interact with either Ras. In
      conclusion, NORE1B suppresses replication and transformation of cells as
      effectively as RASSF1A and thus is a putative tumor suppressor gene. NORE1B
      interacts physically with RASSF1A and functional loss of one of the interacting
      partners may lead to uncontrolled growth and transformation of hepatocytes. This
      may explain the frequent epigenetic silencing of NORE1B and/or RASSF1A in HCC.

PMID- 19118009
TI  - Quantitative analysis of DNA methylation profiles in lung cancer identifies
      aberrant DNA methylation of specific genes and its association with gender and
      cancer risk factors.
AB  - The global increase in lung cancer burden, together with its poor survival and
      resistance to classical chemotherapy, underscores the need for identification of
      critical molecular events involved in lung carcinogenesis. Here, we have applied
      quantitative profiling of DNA methylation states in a panel of five cancer
      associated genes (CDH1, CDKN2A, GSTP1, MTHFR, and RASSF1A) to a large case
      control study of lung cancer. Our analyses revealed a high frequency of aberrant
      hypermethylation of MTHFR, RASSF1A, and CDKN2A in lung tumors as compared with
      control blood samples, whereas no significant increase in methylation levels of
      GSTP1 and CDH1 was observed, consistent with the notion that aberrant DNA
      methylation occurs in a tumor-specific and gene-specific manner. Importantly, we
      found that tobacco smoking, sex, and alcohol intake had a strong influence on the
      methylation levels of distinct genes (RASSF1A and MTHFR), whereas folate intake,
      age, and histologic subtype had no significant influence on methylation states.
      We observed a strong association between MTHFR hypermethylation in lung cancer
      and tobacco smoking, whereas methylation levels of CDH1, CDKN2A, GSTP1, and
      RASSF1A were not associated with smoking, indicating that tobacco smoke targets
      specific genes for hypermethylation. We also found that methylation levels in
      RASSF1A, but not the other genes under study, were influenced by sex, with males
      showing higher levels of methylation. Together, this study identifies aberrant
      DNA methylation patterns in lung cancer and thus exemplifies the mechanism by
      which environmental factors may interact with key genes involved in tumor
      suppression and contribute to lung cancer.

PMID- 19118010
TI  - Role of cyclin D1 as a mediator of c-Met- and beta-catenin-induced
      hepatocarcinogenesis.
AB  - Activation of c-Met signaling and beta-catenin mutations are frequent genetic
      events observed in liver cancer development. Recently, we demonstrated that
      activated beta-catenin can cooperate with c-Met to induce liver cancer formation
      in a mouse model. Cyclin D1 (CCND1) is an important cell cycle regulator that is
      considered to be a downstream target of beta-catenin. To determine the importance
      of CCND1 as a mediator of c-Met- and beta-catenin-induced hepatocarcinogenesis,
      we investigated the genetic interactions between CCND1, beta-catenin, and c-Met
      in liver cancer development using mouse models. We coexpressed CCND1 with c-Met
      in mice and found CCND1 to cooperate with c-Met to promote liver cancer
      formation. Tumors induced by CCND1/c-Met had a longer latency period, formed at a
      lower frequency, and seemed to be more benign compared with those induced by beta
      catenin/c-Met. In addition, when activated beta-catenin and c-Met were coinjected
      into CCND1-null mice, liver tumors developed despite the absence of CCND1.
      Intriguingly, we observed a moderate accelerated tumor growth and increased tumor
      malignancy in these CCND1-null mice. Molecular analysis showed an up-regulation
      of cyclin D2 (CCND2) expression in CCND1-null tumor samples, indicating that
      CCND2 may replace CCND1 in hepatic tumorigenesis. Together, our results suggest
      that CCND1 functions as a mediator of beta-catenin during HCC pathogenesis,
      although other molecules may be required to fully propagate beta-catenin
      signaling. Moreover, our data suggest that CCND1 expression is not essential for
      liver tumor development induced by c-Met and beta-catenin.

PMID- 19118011
TI  - Consistent up-regulation of Stat3 Independently of Jak2 mutations in a new murine
      model of essential thrombocythemia.
AB  - Janus-activated kinase 2 (JAK2) mutations are common in myeloproliferative
      disorders; however, although they are detected in virtually all polycythemia vera
      patients, they are found in approximately 50% of essential thrombocythemia (ET)
      patients, suggesting that converging pathways/abnormalities underlie the onset of
      ET. Recently, the chromosomal translocation 3;21, leading to the fusion gene
      AML1/MDS1/EVI1 (AME), was observed in an ET patient. After we forced the
      expression of AME in the bone marrow (BM) of C57BL/6J mice, all the reconstituted
      mice died of a disease with symptoms similar to ET with a latency of 8 to 16
      months. Peripheral blood smears consistently showed an elevated number of
      dysplastic platelets with anisocytosis, degranulation, and giant size. Although
      the AME-positive mice did not harbor Jak2 mutations, the BM of most of them had
      significantly higher levels of activated Stat3 than the controls. With combined
      biochemical and biological assays we found that AME binds to the Stat3 promoter
      leading to its up-regulation. Signal transducers and activators of transcription
      3 (STAT3) analysis of a small group of ET patients shows that in about half of
      the patients, there is STAT3 hyperactivation independently of JAK2 mutations,
      suggesting that the hyperactivation of STAT3 by JAK2 mutations or promoter
      activation may be a critical step in development of ET.

PMID- 19118012
TI  - Cyclin-dependent kinase-3-mediated c-Jun phosphorylation at Ser63 and Ser73
      enhances cell transformation.
AB  - c-Jun is a component of the activator protein-1 (AP-1) complex, which plays a
      crucial role in the regulation of gene expression, cell proliferation, and cell
      transformation, as well as cancer development. Herein, we found that cyclin
      dependent kinase (Cdk)-3, but not Cdk2 or c-Jun NH(2)-terminal kinase, is a novel
      kinase of c-Jun induced by stimulation with growth factors such as epidermal
      growth factor (EGF). Cdk3 was shown to phosphorylate c-Jun at Ser63 and Ser73 in
      vitro and ex vivo. EGF-induced Cdk3 activation caused c-Jun phosphorylation at
      Ser63 and Ser73, resulting in increased AP-1 transactivation. Ectopic expression
      of Cdk3 resulted in anchorage-independent cell transformation of JB6 Cl41 cells
      induced by EGF and foci formation stimulated by constitutively active Ras
      (Ras(G12V)), which was mediated by AP-1 in NIH3T3 cells. These results showed
      that the Cdk3/c-Jun signaling axis plays an important role in EGF-stimulated cell
      proliferation and cell transformation.

PMID- 19118013
TI  - A multifactorial signature of DNA sequence and polycomb binding predicts aberrant
      CpG island methylation.
AB  - Aberrant CpG island methylation is associated with transcriptional silencing of
      regulatory genes in human cancer. Although most CpG islands remain unmethylated,
      a subset accrues aberrant methylation in cancer via unknown mechanisms.
      Previously, we showed that CpG islands differ in their intrinsic propensity
      towards hypermethylation. We developed a classifier (PatMAn) based on the
      frequencies of seven DNA sequence patterns that discriminated methylation-prone
      (MP) and methylation-resistant (MR) CpG islands. Here, we report on the genome
      wide application and direct testing of PatMAn in cancer. Although trained on data
      from a cell culture model of de novo methylation involving the overexpression of
      DNMT1, PatMAn accurately predicted CpG islands at increased risk of
      hypermethylation in cancer cell lines and primary tumors. Analysis of CpG islands
      predicted to be MP revealed a strong association with embryonic targets of
      polycomb-repressive complex 2 (PRC2), indicating that PatMAn predicts not only
      aberrant methylation, but also PRC2 binding. A second classifier (SUPER-PatMAn)
      that integrates the seven PatMAn DNA patterns with SUZ12 enriched regions as a
      marker of PRC2 occupancy showed improved performance (prediction accuracy, 81
      88%). In addition to many non-PRC2 targets, SUPER-PatMAn identified a subset of
      PRC2 targets that were more likely to be hypermethylated in cancer. Genome-wide,
      CpG islands predicted to be MP were enriched in genes known to undergo
      hypermethylation in cancer, genes functioning in transcriptional regulation, and
      components of developmental pathways. These findings show that hypermethylation
      of certain gene loci is controlled in part by an underlying susceptibility
      influenced by both local sequence context and trans-acting factors.

PMID- 19118014
TI  - High frequency of LMAN1 abnormalities in colorectal tumors with microsatellite
      instability.
AB  - Glycosyl epitopes have been identified as tumor-specific markers in colorectal
      tumors and various lines of evidence indicate the significance of altered
      synthesis, transport, and secretion of glycoproteins in tumorigenesis. However,
      aberrant glycosylation has been largely ignored in microsatellite unstable (MSI
      H) colorectal tumors. Therefore, we analyzed mutation frequencies of genes of the
      cellular glycosylation machinery in MSI-H tumors, focusing on frameshift
      mutations in coding MNRs (cMNRs). Among 28 candidate genes, LMAN1/ERGIC53, a
      mannose-specific lectin mediating endoplasmatic reticulum (ER)-to-Golgi transit
      of glycosylated proteins, showed high mutation frequency in MSI-H colorectal
      cancer cell lines (52%; 12 of 23), carcinomas (45%; 72 of 161), and adenomas
      (40%; 8 of 20). Biallelic mutations were observed in 17% (4 of 23) of MSI-H
      colorectal cancer cell lines. LMAN1 was found to be transcribed but truncated
      protein remained undetectable in these LMAN1-mutant cell lines.
      Immunohistochemical and molecular analysis of LMAN1-mutated carcinomas and
      adenomas revealed regional loss of LMAN1 expression due to biallelic LMAN1 cMNR
      frameshift mutations. In LMAN1-deficient colorectal cancer cell lines, secretion
      of the LMAN1 client protein alpha-1-antitrypsin (A1AT), an inhibitor of
      angiogenesis and tumor growth, was significantly impaired but could be restored
      upon LMAN1 re-expression. These results suggest that LMAN1 mutational
      inactivation is a frequent and early event potentially contributing to MSI-H
      tumorigenesis.

PMID- 19118015
TI  - Identification of novel alternative splice isoforms of circulating proteins in a
      mouse model of human pancreatic cancer.
AB  - To assess the potential of tumor-associated, alternatively spliced gene products
      as a source of biomarkers in biological fluids, we have analyzed a large data set
      of mass spectra derived from the plasma proteome of a mouse model of human
      pancreatic ductal adenocarcinoma. MS/MS spectra were interrogated for novel
      splice isoforms using a nonredundant database containing an exhaustive three
      frame translation of Ensembl transcripts and gene models from ECgene. This
      integrated analysis identified 420 distinct splice isoforms, of which 92 did not
      match any previously annotated mouse protein sequence. We chose seven of those
      novel variants for validation by reverse transcription-PCR. The results were
      concordant with the proteomic analysis. All seven novel peptides were
      successfully amplified in pancreas specimens from both wild-type and mutant mice.
      Isotopic labeling of cysteine-containing peptides from tumor-bearing mice and
      wild-type controls enabled relative quantification of the proteins. Differential
      expression between tumor-bearing and control mice was notable for peptides from
      novel variants of muscle pyruvate kinase, malate dehydrogenase 1, glyceraldehyde
      3-phosphate dehydrogenase, proteoglycan 4, minichromosome maintenance, complex
      component 9, high mobility group box 2, and hepatocyte growth factor activator.
      Our results show that, in a mouse model for human pancreatic cancer, novel and
      differentially expressed alternative splice isoforms are detectable in plasma and
      may be a source of candidate biomarkers.

PMID- 19118016
TI  - The origins of breast cancer prognostic gene expression profiles.
AB  - Recent high profile clinical trials show that microarray-based gene expression
      profiling has the potential to become an important tool for predicting prognosis
      in breast cancer. Earlier work in our laboratory using mouse models and human
      breast cancer populations has enabled us to show that metastasis susceptibility
      is an inherited trait. This same combined approach facilitated the identification
      of a number of candidate genes that, when dysregulated, have the potential to
      induce prognostic gene expression profiles in human data sets. To investigate if
      these gene expression signatures were of somatic or germline origin and to assess
      the contribution of different cell types to the induction of these signatures, we
      have performed a series of expression profiling experiments in a mouse model of
      metastatic breast cancer. These results show that both the tumor epithelium and
      invading stromal tissues contribute to the development of prognostic gene
      signatures. Furthermore, analysis of normal tissues and tumor transplants
      suggests that prognostic signatures result from both somatic and inherited
      components, with the inherited components being more consistently predictive.

PMID- 19118017
TI  - Inducible cutaneous inflammation reveals a protumorigenic role for keratinocyte
      CXCR2 in skin carcinogenesis.
AB  - Transgenic mice that overexpress PKCalpha in the epidermis (K5-PKCalpha mice)
      exhibit acute CXCR2-mediated intraepidermal neutrophilic inflammation and a
      strong epidermal hyperplasia in response to application of 12-O
      tetradecanoylphorbol-13-acetate (TPA). We now show that hyperplasia is
      independent of infiltrating neutrophils. Furthermore, when K5-PKCalpha mice were
      initiated with 7,12-dimethylbenz(a)anthracene (DMBA) and promoted with a low dose
      of TPA, 58% of K5-PKCalpha mice developed skin papillomas that progressed to
      carcinoma, whereas wild-type mice did not develop tumors. We confirmed that CXCR2
      is expressed by keratinocytes and showed that transformation by oncogenic ras (a
      hallmark of DMBA initiation) or TPA exposure induced all CXCR2 ligands. Ras
      induction of CXCR2 ligands was mediated by autocrine activation of epidermal
      growth factor receptor and nuclear factor-kappaB, and potentiated by PKCalpha.
      Oncogenic ras also induced CXCR2 ligands in keratinocytes genetically ablated for
      CXCR2. However, ras transformed CXCR2 null keratinocytes formed only small skin
      tumors in orthotopic skin grafts to CXCR2 intact hosts, whereas transformed wild
      type keratinocytes produced large tumors. In vitro, CXCR2 was essential for CXCR2
      ligand-stimulated migration of ras-transformed keratinocytes and for ligand
      activation of the extracellular signal-regulated kinase (ERK) and Akt pathways.
      Both migration and activation of ERK and Akt were restored by CXCR2
      reconstitution of CXCR2 null keratinocytes. Thus, activation of CXCR2 on ras
      transformed keratinocytes has both promigratory and protumorigenic functions. The
      up-regulation of CXCR2 ligands after initiation by oncogenic ras and promotion
      with TPA in the mouse skin model provides a mechanism to stimulate migration by
      both autocrine and paracrine pathways and contribute to tumor development.

PMID- 19118018
TI  - Interleukin-6 in the bone marrow microenvironment promotes the growth and
      survival of neuroblastoma cells.
AB  - Neuroblastoma, the second most common solid tumor in children, frequently
      metastasizes to the bone marrow and the bone. Neuroblastoma cells present in the
      bone marrow stimulate the expression of interleukin-6 (IL-6) by bone marrow
      stromal cells (BMSC) to activate osteoclasts. Here we have examined whether
      stromal-derived IL-6 also has a paracrine effect on neuroblastoma cells. An
      analysis of the expression of IL-6 and its receptor, IL-6R, in 11 neuroblastoma
      cell lines indicated the expression of IL-6 in 4 cell lines and of IL-6R in 9
      cell lines. Treatment of IL-6R-positive cells with recombinant human IL-6
      resulted in signal transducer and activator of transcription-3 and extracellular
      signal-regulated kinase-1/2 activation. Culturing IL-6R-positive neuroblastoma
      cells in the presence of BMSC or recombinant human IL-6 increased proliferation
      and protected tumor cells from etoposide-induced apoptosis, whereas it had no
      effect on IL-6R-negative tumor cells. In vivo, neuroblastoma tumors grew faster
      in the presence of a paracrine source of IL-6. IL-6 induced the expression of
      cyclooxygenase-2 in neuroblastoma cells with concomitant release of prostaglandin
      E2, which increased the expression of IL-6 by BMSC. Supporting a role for stromal
      derived IL-6 in patients with neuroblastoma bone metastasis, we observed elevated
      levels of IL-6 in the serum and bone marrow of 16 patients with neuroblastoma
      bone metastasis and in BMSC derived from these patients. Altogether, the data
      indicate that stromal-derived IL-6 contributes to the formation of a bone marrow
      microenvironment favorable to the progression of metastatic neuroblastoma.

PMID- 19118019
TI  - Low levels of tumor necrosis factor alpha increase tumor growth by inducing an
      endothelial phenotype of monocytes recruited to the tumor site.
AB  - Microenvironmental cues instruct infiltrating tumor-associated myeloid cells to
      drive malignant progression. A subpopulation of tumor-associated myeloid cells
      coexpressing endothelial and myeloid markers, although rare in peripheral blood,
      are primarily associated with tumors where they enhance tumor growth and
      angiogenesis. These biphenotypic vascular leukocytes result from the endothelial
      differentiation of myeloid progenitors, a process regulated by tumor necrosis
      factor (TNF)alpha in vitro. An in vivo increase in tumor-derived TNFalpha
      expression promoted tumor growth and vascularity of mouse melanoma, lung cancer,
      and mammary tumors. Notably, tumor growth was accompanied by a significant
      increase in myeloid/endothelial biphenotypic populations. TNFalpha-associated
      tumor growth, vascularity, and generation of tumor vascular leukocytes in mouse
      melanoma tumors were dependent on intact host TNFalpha receptors. Importantly,
      TNFalpha-expressing tumors did not exhibit increased inflammation over control
      tumors, suggesting a unique action related to myeloid to endothelial
      differentiation. Our studies suggest that TNFalpha constitutes a tumor
      microenvironment signal that biases recruited monocytes toward a
      proangiogenic/provasculogenic myeloid/endothelial phenotype.

PMID- 19118020
TI  - Vascular endothelial growth factor-C and C-C chemokine receptor 7 in tumor cell
      lymphatic cross-talk promote invasive phenotype.
AB  - Most carcinomas spread to distant sites through lymphatic vessels. Several
      preclinical and clinical studies have shown a positive correlation between the
      incidence of lymph node metastasis and secretion of the lymphatic growth factor
      vascular endothelial growth factor-C (VEGF-C) by tumor cells, suggesting tumor
      lymphangiogenesis as an escape mechanism. However, recent evidence has shown VEGF
      receptor-3 (VEGFR-3) expression on tumor cells and autocrine signaling, which
      increase metastatic potential. Furthermore, there is growing evidence implicating
      lymphatic-homing chemokine receptors, particularly C-C chemokine receptor 7
      (CCR7), in lymph node metastasis. We report here that expressions of VEGF-C and
      CCR7 by tumor cells act synergistically to promote their invasion toward
      lymphatics. First, VEGF-C acts to increase lymphatic secretion of CCL21, which in
      turn drives CCR7-dependent tumor chemoinvasion toward lymphatics. Second, VEGF-C
      acts in an autocrine fashion to increase tumor invasiveness by increasing the
      proteolytic activity and motility of tumor cells in a three-dimensional matrix.
      Both of these effects are VEGFR-3 dependent and evident only in three-dimensional
      environments. We further verified that VEGF-C induces lymphatic CCL21 up
      regulation in vivo by direct injection of VEGF-C protein intradermally in the
      mouse. Taken together, these results bridge the prometastatic functions of CCR7
      and VEGF-C in tumors and show that, beyond lymphangiogenesis, VEGF-C promotes
      tumor invasion toward lymphatics by both autocrine and CCR7-dependent paracrine
      signaling mechanisms, which may be a significant cause of lymph node metastasis.

PMID- 19118021
TI  - Hypoxia-inducible carbonic anhydrase IX and XII promote tumor cell growth by
      counteracting acidosis through the regulation of the intracellular pH.
AB  - Acidosis of the tumor microenvironment is typical of a malignant phenotype,
      particularly in hypoxic tumors. All cells express multiple isoforms of carbonic
      anhydrase (CA), enzymes catalyzing the reversible hydration of carbon dioxide
      into bicarbonate and protons. Tumor cells express membrane-bound CAIX and CAXII
      that are controlled via the hypoxia-inducible factor (HIF). Despite the
      recognition that tumor expression of HIF-1alpha and CAIX correlates with poor
      patient survival, the role of CAIX and CAXII in tumor growth is not fully
      resolved. To understand the advantage that tumor cells derive from expression of
      both CAIX and CAXII, we set up experiments to either force or invalidate the
      expression of these enzymes. In hypoxic LS174Tr tumor cells expressing either one
      or both CA isoforms, we show that (a) in response to a "CO(2) load," both CAs
      contribute to extracellular acidification and (b) both contribute to maintain a
      more alkaline resting intracellular pH (pH(i)), an action that preserves ATP
      levels and cell survival in a range of acidic outside pH (6.0-6.8) and low
      bicarbonate medium. In vivo experiments show that ca9 silencing alone leads to a
      40% reduction in xenograft tumor volume with up-regulation of ca12 mRNA levels,
      whereas invalidation of both CAIX and CAXII gives an impressive 85% reduction.
      Thus, hypoxia-induced CAIX and CAXII are major tumor prosurvival pH(i)-regulating
      enzymes, and their combined targeting shows that they hold potential as
      anticancer targets.

PMID- 19118022
TI  - Paracrine signaling by platelet-derived growth factor-CC promotes tumor growth by
      recruitment of cancer-associated fibroblasts.
AB  - Cancer results from the concerted performance of malignant cells and stromal
      cells. Cell types populating the microenvironment are enlisted by the tumor to
      secrete a host of growth-promoting cues, thus upholding tumor initiation and
      progression. Platelet-derived growth factors (PDGF) support the formation of a
      prominent tumor stromal compartment by as of yet unidentified molecular
      effectors. Whereas PDGF-CC induces fibroblast reactivity and fibrosis in a range
      of tissues, little is known about the function of PDGF-CC in shaping the tumor
      stroma interplay. Herein, we present evidence for a paracrine signaling network
      involving PDGF-CC and PDGF receptor-alpha in malignant melanoma. Expression of
      PDGFC in a mouse model accelerated tumor growth through recruitment and
      activation of different subsets of cancer-associated fibroblasts. In seeking the
      molecular identity of the supporting factors provided by cancer-associated
      fibroblasts, we made use of antibody arrays and an in vivo coinjection model to
      identify osteopontin as the effector of the augmented tumor growth induced by
      PDGF-CC. In conclusion, we establish paracrine signaling by PDGF-CC as a
      potential drug target to reduce stromal support in malignant melanoma.

PMID- 19118024
TI  - Comment re: Cancer incidence falls for oldest.

PMID- 19118025
TI  - Setting the standard for translational cancer research.

PMID- 19118026
TI  - Peroxisome proliferator-activated receptor gamma pathway targeting in
      carcinogenesis: implications for chemoprevention.
AB  - The peroxisome proliferator-activated receptor (PPAR) gamma is one member of the
      nuclear receptor superfamily that contains in excess of 80 described receptors.
      PPARgamma activators are a diverse group of agents that range from endogenous
      fatty acids or derivatives (linolenic, linoleic, and 15-deoxy-Delta(12,14)
      prostaglandin J(2)) to Food and Drug Administration-approved thiazolidinedione
      drugs [pioglitazone (Actos) and rosiglitazone (Avandia)] for the treatment of
      diabetes. Once activated, PPARgamma will preferentially bind with retinoid X
      receptor alpha and signal antiproliferative, antiangiogenic, and
      prodifferentiation pathways in several tissue types, thus making it a highly
      useful target for down-regulation of carcinogenesis. Although PPAR-gamma
      activators show many anticancer effects on cell lines, their advancement into
      human advanced cancer clinical trials has met with limited success. This article
      will review translational findings in PPARgamma activation and targeting in
      carcinogenesis prevention as they relate to the potential use of PPARgamma
      activators clinically as cancer chemoprevention strategies.

PMID- 19118027
TI  - Heat shock protein 90 as a drug target: some like it hot.
AB  - Heat shock protein 90 (HSP90) is a ubiquitously expressed chaperone that is
      involved in the posttranslational folding and stability of proteins. Inhibition
      at the NH(2)-terminal ATP-binding site leads to the degradation of client
      proteins by the ubiquitin proteasome pathway. Inhibition of HSP90 leads to the
      degradation of known oncogenes, such as ERB-B2, BRAF, and BCR-ABL, leading to the
      combinatorial blockade of multiple signal transduction pathways, such as the RAS
      RAF-mitogen-activated protein/extracellular signal-regulated kinase kinase
      extracellular signal-regulated kinase and phosphatidylinositol 3-kinase pathways.
      Multiple structurally diverse HSP90 inhibitors are undergoing early clinical
      evaluation. The clinical focus of these drugs should be solid tumors, such as
      breast, prostate, and lung cancers, along with malignant melanoma, in addition to
      hematologic malignancies, such as chronic myeloid leukemia and multiple myeloma.
      HSP90 inhibitors can be used as single agents or in combination with other
      targeted treatments or conventional forms of treatment such as chemotherapy and
      radiotherapy. Clinical trials evaluating efficacy of these agents should include
      innovative designs to capture cytostasis evidenced by clinical nonprogression and
      enrichment of patient populations by molecular characterization. The results of
      clinical trials evaluating the efficacy of drugs targeting this exciting target
      are awaited.

PMID- 19118028
TI  - Clinical implications of CYP2D6 genotyping in tamoxifen treatment for breast
      cancer.
AB  - In October 2006 the Food and Drug Administration recommended an update in the
      tamoxifen label to reflect the increased risk of recurrence in breast cancer
      patients who are cytochrome P450 2D6 (CYP2D6) poor metabolizers. This
      recommendation was based on only a few studies at that time. More clinical
      studies addressing the relation between the CYP2D6 genotype and tamoxifen
      efficacy have been published since, mostly describing Caucasian populations in
      the adjuvant treatment setting. An updated analysis of the literature is
      presented. Furthermore, the possibility to implement CYP2D6 genotyping in
      clinical practice is evaluated by analyzing the results of six studies on mainly
      Caucasian patients using adjuvant tamoxifen. Three studies were consistent with
      the FDA advice, but the three other studies showed contradictory results.
      Although some of the published criticism on the negative studies is justified,
      this does not imply that these results should be discarded. The reviewed
      literature is put in perspective acknowledging the limiting effect of Mendelian
      randomization on confounding and the limitations of the various study designs.
      The current accumulation of data showing worse clinical outcome in patients with
      decreased CYP2D6 metabolism in other types of populations still indicates that
      the CYP2D6 genotype may well become a clinically relevant predictive marker. The
      CYP2D6 genotype might be one of the first predictors of therapeutic response in
      cancer care based on germline DNA creating the possibility to analyze blood
      instead of tumor.

PMID- 19118029
TI  - S100A2 induces metastasis in non-small cell lung cancer.
AB  - PURPOSE: S100 proteins are implicated in metastasis development in several
      cancers. In this study, we analyzed the prognostic role of mRNA levels of all
      S100 proteins in early stage non-small cell lung cancer (NSCLC) patients as well
      as the pathogenetic of S100A2 in the development of metastasis in NSCLC.
      EXPERIMENTAL DESIGN: Microarray data from a large NSCLC patient cohort was
      analyzed for the prognostic role of S100 proteins for survival in surgically
      resected NSCLC. Metastatic potential of the S100A2 gene was analyzed in vitro and
      in a lung cancer mouse model in vivo. Overexpression and RNAi approaches were
      used for analysis of the biological functions of S100A2. RESULTS: High mRNA
      expression levels of several S100 proteins and especially S100A2 were associated
      with poor survival in surgically resected NSCLC patients. Upon stable
      transfection into NSCLC cell lines, S100A2 did not alter proliferation. However,
      S100A2 enhanced transwell migration as well as transendothelial migration in
      vitro. NOD/SCID mice injected s.c. with NSCLC cells overexpressing S100A2
      developed significantly more distant metastasis (64%) than mice with control
      vector transfected tumor cells (17%; P < 0.05). When mice with S100A2 expressing
      tumors were treated i.v. with shRNA against S100A2, these mice developed
      significantly fewer lung metastasis than mice treated with control shRNA (P =
      0.021). CONCLUSIONS: These findings identify S100A2 as a strong metastasis
      inducer in vivo. S100A2 might be a potential biomarker as well as a novel
      therapeutic target in NSCLC metastasis.

PMID- 19118030
TI  - Array comparative genomic hybridization analysis of PTCL-U reveals a distinct
      subgroup with genetic alterations similar to lymphoma-type adult T-cell
      leukemia/lymphoma.
AB  - PURPOSE: Peripheral T-cell lymphoma, unspecified (PTCL-U) comprises
      histopathologically and clinically heterogeneous groups. The purpose of this
      study was to identify subgroups with distinct genetic, histopathologic, and
      prognostic features. EXPERIMENTAL DESIGN: We used array comparative genomic
      hybridization (CGH) for high-resolution analysis of 51 PTCL-U patients and the
      array data for examining possible correlations of histopathologic and clinical
      features. Moreover, we compared the genetic, histopathologic, and prognostic
      features of the PTCL-U cases with those of 59 cases of lymphoma-type adult T-cell
      leukemia/lymphoma (ATLL). RESULTS: We identified 32 regions with frequent genomic
      imbalance, 1 region with high copy number gain at 14q32.2, and 1 region with
      homozygous loss at 9p21.3. Gains of 7p and 7q and loss of 9p21.3 showed a
      significant association with poor prognosis. PTCL-U cases with genomic imbalance
      showed distinct histopathologic and prognostic features compared with such cases
      without alteration and a marked genetic, histopathologic, and prognostic
      resemblance to lymphoma-type ATLL. CONCLUSIONS: The array CGH enabled us to
      identify the frequently altered genomic regions with strong prognostic power
      among PTCL-U cases. A correlative analysis using the array CGH data disclosed a
      subgroup in PTCL-U with genomic alterations and with histopathologic and clinical
      relevance. In addition to histopathologic similarity, the strong genetic and
      prognostic resemblance between PTCL-U cases with genomic imbalance detected by
      array CGH and lymphoma-type ATLL seems to support the notion that the former may
      constitute a distinct PTCL-U subgroup.

PMID- 19118031
TI  - In vivo knockdown of the androgen receptor results in growth inhibition and
      regression of well-established, castration-resistant prostate tumors.
AB  - PURPOSE: Progression to the castration-resistant state is the incurable and
      lethal end stage of prostate cancer, and there is strong evidence that androgen
      receptor (AR) still plays a central role in this process. We hypothesize that
      knocking down AR will have a major effect on inhibiting growth of castration
      resistant tumors. EXPERIMENTAL DESIGN: Castration-resistant C4-2 human prostate
      cancer cells stably expressing a tetracycline-inducible AR-targeted short hairpin
      RNA (shRNA) were generated to directly test the effects of AR knockdown in C4-2
      human prostate cancer cells and tumors. RESULTS: In vitro expression of AR shRNA
      resulted in decreased levels of AR mRNA and protein, decreased expression of
      prostate-specific antigen (PSA), reduced activation of the PSA-luciferase
      reporter, and growth inhibition of C4-2 cells. Gene microarray analyses revealed
      that AR knockdown under hormone-deprived conditions resulted in activation of
      genes involved in apoptosis, cell cycle regulation, protein synthesis, and
      tumorigenesis. To ensure that tumors were truly castration-resistant in vivo,
      inducible AR shRNA expressing C4-2 tumors were grown in castrated mice to an
      average volume of 450 mm(3). In all of the animals, serum PSA decreased, and in
      50% of them, there was complete tumor regression and disappearance of serum PSA.
      CONCLUSIONS: Whereas castration is ineffective in castration-resistant prostate
      tumors, knockdown of AR can decrease serum PSA, inhibit tumor growth, and
      frequently cause tumor regression. This study is the first direct evidence that
      knockdown of AR is a viable therapeutic strategy for treatment of prostate tumors
      that have already progressed to the castration-resistant state.

PMID- 19118032
TI  - Intracellular clusterin inhibits mitochondrial apoptosis by suppressing p53
      activating stress signals and stabilizing the cytosolic Ku70-Bax protein complex.
AB  - PURPOSE: Secretory clusterin (sCLU)/apolipoprotein J is an extracellular
      chaperone that has been functionally implicated in DNA repair, cell cycle
      regulation, apoptotic cell death, and tumorigenesis. It exerts a prosurvival
      function against most therapeutic treatments for cancer and is currently an
      antisense target in clinical trials for tumor therapy. However, the molecular
      mechanisms underlying its function remained largely unknown. EXPERIMENTAL DESIGN:
      The molecular effects of small interfering RNA-mediated sCLU depletion in
      nonstressed human cancer cells were examined by focusing entirely on the
      endogenously expressed sCLU protein molecules and combining molecular,
      biochemical, and microscopic approaches. RESULTS: We report here that sCLU
      depletion in nonstressed human cancer cells signals stress that induces p53
      dependent growth retardation and high rates of endogenous apoptosis. We
      discovered that increased apoptosis in sCLU-depleted cells correlates to altered
      ratios of proapoptotic to antiapoptotic Bcl-2 protein family members, is
      amplified by p53, and is executed by mitochondrial dysfunction. sCLU depletion
      related stress signals originate from several sites, because sCLU is an integral
      component of not only the secretory pathway but also the nucleocytosolic
      continuum and mitochondria. In the cytoplasm, sCLU depletion disrupts the Ku70
      Bax complex and triggers Bax activation and relocation to mitochondria. We show
      that sCLU binds and thereby stabilizes the Ku70-Bax protein complex serving as a
      cytosol retention factor for Bax. CONCLUSIONS: We suggest that elevated sCLU
      levels may enhance tumorigenesis by interfering with Bax proapoptotic activities
      and contribute to one of the major characteristics of cancer cells, that is,
      resistance to apoptosis.

PMID- 19118034
TI  - Niche-dependent tumorigenic capacity of malignant ovarian ascites-derived cancer
      cell subpopulations.
AB  - PURPOSE: In previous studies, we have used human embryonic stem cells (hESC) to
      generate a tissue microenvironment in immunocompromised mice as an experimental
      approach for studying human tumorigenesis. We now examine the attributes of such
      a cellular microenvironment in supporting the growth of human cancer cells
      freshly harvested from malignant ovarian ascites and to determine whether there
      are differences among subsets of ascites-derived cancer cells in terms of
      tumorigenic capacity in the conventional murine xenograft model and in the hESC
      derived microenvironment. EXPERIMENTAL DESIGN: Freshly harvested malignant
      ovarian ascites-derived cancer cells and six derivative ovarian cancer cell
      subpopulations (CCSP) were characterized for ovarian cancer-associated biomarker
      expression both in vitro and in vivo and for their capacity to generate tumors in
      the two models. RESULTS: Ovarian cancer-associated biomarkers were detected in
      the ascites-derived cancer cells and in the six newly established CCSPs.
      Nevertheless, certain CCSPs that did not develop into tumors in a conventional
      murine xenograft model did generate tumors in the hESC-derived cellular
      microenvironment, indicating variable niche dependency for the tumorigenic
      capacity of the different CCSPs. The hESC-derived microenvironment provided an
      improved niche for supporting growth of certain tumor cell subpopulations.
      CONCLUSIONS: The results highlight the experimental utility of the hESC-derived
      cellular microenvironment to enable functional distinction of CCSPs, including
      the identification of cells that do not grow into a tumor in the conventional
      direct tumor xenograft platform, thereby rendering such cells accessible to
      characterization and testing of anticancer therapies.

PMID- 19118033
TI  - Proapoptotic function of integrin beta(3) in human hepatocellular carcinoma
      cells.
AB  - PURPOSE: This study evaluates the proapoptotic function of integrin beta(3) in
      human hepatocellular carcinoma (HCC). EXPERIMENTAL DESIGN: The expression of
      integrin beta(3) in 67 HCC specimens paired with corresponding neighboring
      nontumorous tissue was studied by quantitative real-time PCR and Western blot.
      The proapoptotic function of integrin beta(3) in SMMC-7721 human hepatoma cells
      overexpressing ITGB3 (gene coding integrin beta(3)) was determined through colony
      formation, serum starvation, and anoikis assay. RESULTS: Compared with
      neighboring pathologically normal liver tissue, approximately 60% of the HCC
      specimens showed a significant down-regulated level of integrin beta(3)
      expression. Transient expression of integrin beta(3) in SMMC-7721 resulted in an
      enhanced level of apoptosis and suppression of colony formation. Cell growth
      inhibition on serum/ligand deprivation and incidences of anoikis were remarkably
      increased in SMMC-7721 with stable expression of integrin beta(3) in comparison
      with vector control transfectants. In addition, expression of fibrinogen and
      vitronectin, two native ligands for integrin alpha(v)beta(3) in liver, was
      inhibited, which was correlated with the decreased integrin beta(3) expression.
      Replenishing these ligands to the starved SMMC-7721 stable transfectants
      effectively restored the proapoptotic function of integrin beta(3). CONCLUSIONS:
      Down-regulation of integrin beta(3) and its ligands in liver is related to the
      aggressive growth of HCC. Thus, reconstitution of integrin beta(3) in HCC may be
      a potential therapeutic approach to inhibit aggressive growth of liver cancer.

PMID- 19118035
TI  - Cytoplasmic sequestration of p27 via AKT phosphorylation in renal cell carcinoma.
AB  - PURPOSE: p27 localization and expression has prognostic and predictive value in
      cancer. Little is known regarding expression patterns of p27 in renal cell
      carcinoma (RCC) or how p27 participates in disease progression or response to
      therapy. EXPERIMENTAL DESIGN: RCC-derived cell lines, primary tumors, and normal
      renal epithelial cells were analyzed for p27 expression, phosphorylation (T157 of
      the NLS), and subcellular localization. RCC-derived cell lines were treated with
      phosphatidylinositol 3-kinase (PI3K) and mammalian target of rapamycin (mTOR)
      inhibitors and effects on p27 localization were assessed. The potential
      contribution of cytoplasmic p27 to resistance to apoptosis was also evaluated.
      RESULTS: p27 was elevated in tumors compared with matched controls, and
      cytoplasmic mislocalization of p27 was associated with increasing tumor grade.
      Cytoplasmic localization of p27 correlated with phosphorylation at T157, an AKT
      phosphorylation site in the p27 NLS. In RCC cell lines, activated PI3K/AKT
      signaling was accompanied by mislocalization of p27. AKT activation and
      phosphorylation of p27 was associated with resistance to apoptosis, and small
      interfering RNA knockdown of p27 or relocalization to the nucleus increased
      apoptosis in RCC cells. Treatment with the PI3K inhibitors LY294002 or wortmannin
      resulted in nuclear relocalization of p27, whereas mTOR inhibition by rapamycin
      did not. CONCLUSIONS: In RCC, p27 is phosphorylated at T157 of the NLS, with
      increasing tumor grade associated with cytoplasmic p27. PI3K inhibition (which
      reduces AKT activity) reduces T157 phosphorylation and induces nuclear
      relocalization of p27, whereas mTOR inhibition does not. Clinical testing of
      these findings may provide a rational approach for use of mTOR and PI3K/AKT
      pathway inhibitors in patients with RCC.

PMID- 19118036
TI  - Histone deacetylase 8 in neuroblastoma tumorigenesis.
AB  - PURPOSE: The effects of pan-histone deacetylase (HDAC) inhibitors on cancer cells
      have shown that HDACs are involved in fundamental tumor biological processes such
      as cell cycle control, differentiation, and apoptosis. However, because of the
      unselective nature of these compounds, little is known about the contribution of
      individual HDAC family members to tumorigenesis and progression. The purpose of
      this study was to evaluate the role of individual HDACs in neuroblastoma
      tumorigenesis. EXPERIMENTAL DESIGN: We have investigated the mRNA expression of
      all HDAC1-11 family members in a large cohort of primary neuroblastoma samples
      covering the full spectrum of the disease. HDACs associated with disease stage
      and survival were subsequently functionally evaluated in cell culture models.
      RESULTS: Only HDAC8 expression was significantly correlated with advanced disease
      and metastasis and down-regulated in stage 4S neuroblastoma associated with
      spontaneous regression. High HDAC8 expression was associated with poor prognostic
      markers and poor overall and event-free survival. The knockdown of HDAC8 resulted
      in the inhibition of proliferation, reduced clonogenic growth, cell cycle arrest,
      and differentiation in cultured neuroblastoma cells. The treatment of
      neuroblastoma cell lines as well as short-term-culture neuroblastoma cells with
      an HDAC8-selective small-molecule inhibitor inhibited cell proliferation and
      clone formation, induced differentiation, and thus reproduced the HDAC8 knockdown
      phenotype. Global histone 4 acetylation was not affected by HDAC8 knockdown or by
      selective inhibitor treatment. CONCLUSIONS: Our data point toward an important
      role of HDAC8 in neuroblastoma pathogenesis and identify this HDAC family member
      as a specific drug target for the differentiation therapy of neuroblastoma.

PMID- 19118037
TI  - Intracellular MUC1 peptides inhibit cancer progression.
AB  - PURPOSE: During cancer progression, the oncoprotein MUC1 binds beta-catenin while
      simultaneously inhibiting the degradation of the epidermal growth factor receptor
      (EGFR), resulting in enhanced transformation and metastasis. The purpose of this
      study was to design a peptide-based therapy that would block these intracellular
      protein-protein interactions as a treatment for metastatic breast cancer.
      EXPERIMENTAL DESIGN: The amino acid residues responsible for these interactions
      lie in tandem in the cytoplasmic domain of MUC1, and we have targeted this
      sequence to produce a MUC1 peptide that blocks the protumorigenic functions of
      MUC1. We designed the MUC1 inhibitory peptide (MIP) to block the intracellular
      interactions between MUC1/beta-catenin and MUC1/EGFR. To allow for cellular
      uptake we synthesized MIP adjacent to the protein transduction domain, PTD4
      (PMIP). RESULTS: We have found that PMIP acts in a dominant-negative fashion,
      blocking both MUC1/beta-catenin and MUC1/EGFR interactions. In addition, PMIP
      induces ligand-dependent reduction of EGFR levels. These effects correspond to a
      significant reduction in proliferation, migration, and invasion of metastatic
      breast cancer cells in vitro, and inhibition of tumor growth and recurrence in an
      established MDA-MB-231 immunocompromised (SCID) mouse model. Importantly, PMIP
      also inhibits genetically driven breast cancer progression, as injection of tumor
      bearing MMTV-pyV mT transgenic mice with PMIP results in tumor regression and a
      significant inhibition of tumor growth rate. CONCLUSIONS: These data show that
      intracellular MUC1 peptides possess significant antitumor activity and have
      important clinical applications in the treatment of cancer.

PMID- 19118038
TI  - Broad antitumor activity in breast cancer xenografts by motesanib, a highly
      selective, oral inhibitor of vascular endothelial growth factor, platelet-derived
      growth factor, and Kit receptors.
AB  - PURPOSE: Angiogenesis plays a critical role in breast cancer development and
      progression. Vascular endothelial growth factor (VEGF) is a potent angiogenic
      factor that regulates endothelial cell proliferation and survival. We
      investigated the effects of motesanib, a novel, oral inhibitor of VEGF receptors
      1, 2, and 3; platelet-derived growth factor receptor; and Kit receptor, on the
      growth of xenografts representing various human breast cancer subtypes.
      EXPERIMENTAL DESIGN: Athymic nude mice were implanted with MCF-7 (luminal) or MDA
      MB-231 (mesenchymal) tumor fragments or Cal-51 (mixed/progenitor) tumor cells.
      Once tumors were established, animals were randomized to receive increasing doses
      of motesanib alone or motesanib plus cytotoxic chemotherapy (docetaxel,
      doxorubicin, or tamoxifen). RESULTS: Across all three xenograft models, motesanib
      treatment resulted in significant dose-dependent reductions in tumor growth,
      compared with vehicle-treated controls, and in marked reductions in viable tumor
      fraction and blood vessel density. No significant effect on body weight was
      observed with compound treatment compared with control-treated animals. Motesanib
      did not affect the proliferation of tumor cells in vitro. There was a
      significantly greater reduction in xenograft tumor growth when motesanib was
      combined with docetaxel (MDA-MB-231 tumors) or with the estrogen receptor
      modulator tamoxifen (MCF-7 tumors), compared with either treatment alone, but not
      when combined with doxorubicin (Cal-51 tumors). CONCLUSIONS: Treatment with
      motesanib alone or in combination with chemotherapy inhibits tumor growth in vivo
      in various models of human breast cancer. These data suggest that motesanib may
      have broad utility in the treatment of human breast cancer.

PMID- 19118039
TI  - Preferential killing of breast tumor initiating cells by N,N-diethyl-2-[4
      (phenylmethyl)phenoxy]ethanamine/tesmilifene.
AB  - PURPOSE: N,N-Diethyl-2-[4-(phenylmethyl)phenoxy]ethanamine (DPPE; tesmilifene) is
      thought to potentiate the antineoplastic effect of cytotoxic drugs. In a phase
      III randomized trial for metastatic breast cancer using doxorubicin with or
      without DPPE, addition of the latter resulted in a significant improvement in
      overall survival and a trend toward a difference in progression-free survival
      but, paradoxically, no difference in objective tumor response. Here we tested the
      hypothesis that DPPE targets breast tumor-initiating cells (TICs). EXPERIMENTAL
      DESIGN: Human breast TICs from pleural effusions were identified as CD44(+):CD24(
      /low) cells by flow cytometry and functionally by their ability to form
      nonadherent spheres in culture. Mouse mammary TICs from two different models of
      breast cancer were identified as cells capable of initiating spheres in culture
      and secondary tumors following transplantation into the mammary gland of
      syngeneic mice. RESULTS: We show that at physiologically attainable
      concentrations, treatment with DPPE alone reduced tumorsphere formation and
      viability of CD44(+):CD24(-/low) breast cancer cells. The kinetics of killing
      varied for the different breast tumor cells and required continuous exposure to
      the drug. Whereas doxorubicin killed CD44(+):CD24(-/low) and CD44(-):CD24(+)
      cells equally well, DPPE induced apoptosis preferentially in CD44(+):CD24(-/low)
      cells. Treatment of Her2/Neu(+) mammary tumor cells with DPPE in vitro
      efficiently killed TICs, as determined by flow cytometry and transplantation
      assays; DPPE further cooperated with doxorubicin to completely eradicate
      tumorigenic cells. CONCLUSIONS: Our results show that continuous treatment with
      DPPE alone directly targets breast TICs, and provide rationale to test for
      cooperation between DPPE and known drugs with efficacy toward breast cancer
      subtypes.

PMID- 19118040
TI  - Intratumoral delivery of beta-lapachone via polymer implants for prostate cancer
      therapy.
AB  - PURPOSE: beta-Lapachone (ARQ 501, a formulation of beta-lapachone complexed with
      hydroxypropyl-beta-cyclodextrin) is a novel anticancer agent with selectivity
      against prostate cancer cells overexpressing the NAD(P)H:quinone oxidoreductase-1
      enzyme. Lack of solubility and an efficient drug delivery strategy limits this
      compound in clinical applications. In this study, we aimed to develop beta
      lapachone-containing polymer implants (millirods) for direct implantation into
      prostate tumors to test the hypothesis that the combination of a tumor-specific
      anticancer agent with site-specific release of the agent will lead to significant
      antitumor efficacy. EXPERIMENTAL DESIGN: Survival assays in vitro were used to
      test the killing effect of beta-lapachone in different prostate cancer cells.
      beta-Lapachone release kinetics from millirods was determined in vitro and in
      vivo. PC-3 prostate tumor xenografts in athymic nude mice were used for antitumor
      efficacy studies in vivo. RESULTS: beta-Lapachone killed three different prostate
      cancer cell lines in an NAD(P)H:quinone oxidoreductase-1-dependent manner. Upon
      incorporation of solid-state inclusion complexes of beta-lapachone with
      hydroxypropyl-beta-cyclodextrin into poly(D,L-lactide-co-glycolide) millirods,
      beta-lapachone release kinetics in vivo showed a burst release of approximately
      0.5 mg within 12 hours and a subsequently sustained release of the drug (
      approximately 0.4 mg/kg/d) comparable with that observed in vitro. Antitumor
      efficacy studies showed significant tumor growth inhibition by beta-lapachone
      millirods compared with controls (P < 0.0001; n = 10 per group). Kaplan-Meier
      survival curves showed that tumor-bearing mice treated with beta-lapachone
      millirods survived nearly 2-fold longer than controls, without observable
      systemic toxicity. CONCLUSIONS: Intratumoral delivery of beta-lapachone using
      polymer millirods showed the promising therapeutic potential for human prostate
      tumors.

PMID- 19118041
TI  - Induction of apoptosis in human leukemia cells by grape seed extract occurs via
      activation of c-Jun NH2-terminal kinase.
AB  - PURPOSE: To characterize the functional role of c-Jun NH(2)-terminal kinase (JNK)
      and other apoptotic pathways in grape seed extract (GSE)-induced apoptosis in
      human leukemia cells by using pharmacologic and genetic approaches. EXPERIMENTAL
      DESIGN: Jurkat cells were treated with various concentrations of GSE for 12 and
      24 h or with 50 microg/mL GSE for various time intervals, after which apoptosis,
      caspase activation, and cell signaling pathways were evaluated. Parallel studies
      were done in U937 and HL-60 human leukemia cells. RESULTS: Exposure of Jurkat
      cells to GSE resulted in dose- and time-dependent increase in apoptosis and
      caspase activation, events associated with the pronounced increase in Cip1/p21
      protein level. Furthermore, treatment of Jurkat cells with GSE resulted in marked
      increase in levels of phospho-JNK. Conversely, interruption of the JNK pathway by
      pharmacologic inhibitor (e.g., SP600125) or genetic (e.g., small interfering RNA)
      approaches displayed significant protection against GSE-mediated lethality in
      Jurkat cells. CONCLUSIONS: The result of the present study showed that GSE
      induces apoptosis in Jurkat cells through a process that involves sustained JNK
      activation and Cip1/p21 up-regulation, culminating in caspase activation.

PMID- 19118042
TI  - BH3 mimetic obatoclax enhances TRAIL-mediated apoptosis in human pancreatic
      cancer cells.
AB  - PURPOSE: Prosurvival Bcl-2 proteins inhibit the mitochondrial and death receptor
      mediated apoptotic pathways. Obatoclax is a small-molecule antagonist of the BH3
      binding groove of Bcl-2 proteins that may enhance tumor necrosis factor-related
      apoptosis-inducing ligand (TRAIL) sensitivity and efficacy. EXPERIMENTAL DESIGN:
      Human pancreatic cancer cell lines were incubated with obatoclax and/or TRAIL and
      cell viability, Annexin V labeling, caspase cleavage, and cytochrome c release
      were measured. In drug-treated cell lines, protein-protein interactions were
      studied by immunoprecipitation. Bax/Bak activation was analyzed using
      conformation-specific antibodies. Lentiviral short hairpin RNA was used to
      knockdown Bim, Bid, and apoptosis-inducing factor (AIF) expression. RESULTS:
      Obatoclax reduced the viability of PANC-1 and BxPC-3 cell lines and
      synergistically enhanced TRAIL-mediated cytotoxicity. Obatoclax enhanced TRAIL
      mediated apoptosis, as shown by Annexin V labeling, which was accompanied by
      caspase activation (caspase-8, -9, and -3) and cleavage of Bid. Obatoclax
      potentiated TRAIL-mediated Bax/Bak activation and the release of mitochondrial
      cytochrome c, Smac, and AIF. Mechanisms underlying the apoptotic effect of
      obatoclax include displacement of Bak from its sequestration by Bcl-x(L) or Mcl-1
      and release of Bim from Bcl-2 or Mcl-1. Bid knockdown by short hairpin RNA
      attenuated caspase cleavage and cytotoxicity of obatoclax plus TRAIL. Bim
      knockdown failed to inhibit the cytotoxic effect of obatoclax alone or combined
      with TRAIL yet attenuated TRAIL-mediated cytotoxicity. AIF knockdown attenuated
      cytotoxicity of the drug combination. CONCLUSIONS: Obatoclax potentiates TRAIL
      mediated apoptosis by unsequestering Bak and Bim from Bcl-2/Bcl-x(L) or Mcl-1
      proteins. This drug combination enhances Bid-mediated cross-talk between the
      mitochondrial and death receptor-mediated apoptotic pathways and may represent a
      novel therapeutic strategy against pancreatic cancer.

PMID- 19118043
TI  - Reoxygenation of hypoxic glioblastoma multiforme cells potentiates the killing
      effect of an interleukin-13-based cytotoxin.
AB  - PURPOSE: Hypoxia is a cause for resistance to cancer therapies. Molecularly
      targeted recombinant cytotoxins have shown clinical efficacy in the treatment of
      patients with primary brain tumors, glioblastoma multiforme, but it is not known
      whether hypoxia influences their antitumor effect. EXPERIMENTAL DESIGN: We have
      exposed glioblastoma multiforme cells, such as U-251 MG, U-373 MG, SNB-19, and A
      172 MG, to either anoxia or hypoxia and then reoxygenated them while treating
      with an interleukin (IL)-13-based diphtheria toxin (DT)-containing cytotoxin, DT
      IL13QM. We measured the levels of immunoreactive IL-13Ralpha2, a receptor that
      mediates IL-13-cytotoxin cell killing, and the levels of active form of furin, a
      protease that activates the bacterial toxin portion in a cytotoxin. RESULTS: We
      found that anoxia/hypoxia significantly alters the responsiveness of glioblastoma
      multiforme cells to DT-IL13QM. Interestingly, bringing these cells back to
      normoxia caused them to become even more susceptible to the cytotoxin than the
      cells maintained under normoxia. Anoxia/hypoxia caused a highly prominent
      decrease in the immunoreactive levels of both IL-13R and active forms of furin,
      and reoxygenation not only restored their levels but also became higher than that
      in normoxic glioblastoma multiforme cells. CONCLUSIONS: Our results show that a
      recombinant cytotoxin directed against glioblastoma multiforme cells kills these
      cells much less efficiently under anoxic/hypoxic conditions. The reoxygenation
      brings unexpected additional benefit of making glioblastoma multiforme cells even
      more responsive to the killing effect of a cytotoxin.

PMID- 19118044
TI  - Characterization of genetically modified T-cell receptors that recognize the
      CEA:691-699 peptide in the context of HLA-A2.1 on human colorectal cancer cells.
AB  - PURPOSE: Carcinoembryonic antigen (CEA) is a tumor-associated protein expressed
      on a variety of adenocarcinomas. To develop an immunotherapy for patients with
      cancers that overexpress CEA, we isolated and genetically modified a T-cell
      receptors (TCRs) that specifically bound a CEA peptide on human cancer cells.
      EXPERIMENTAL DESIGN: HLA-A2.1 transgenic mice were immunized with CEA:691-699. A
      CEA-reactive TCR was isolated from splenocytes of these mice and was genetically
      introduced into human peripheral blood lymphocytes via RNA electroporation or
      retroviral transduction. Amino acid substitutions were introduced throughout the
      complementarity determining regions (CDR1, CDR2, and CDR3) of both TCR alpha and
      beta chains to improve recognition of CEA. RESULTS: Murine lymphocytes bearing
      the CEA-reactive TCR specifically recognized peptide-loaded T2 cells and HLA
      A2.1(+) CEA(+) human colon cancer cells. Both CD8(+) and CD4(+) human lymphocytes
      expressing the murine TCR specifically recognized peptide-loaded T2 cells.
      However, only gene-modified CD8(+) lymphocytes specifically recognized HLA
      A2.1(+) CEA(+) colon cancer cell lines, and tumor cell recognition was weak and
      variable. We identified two substitutions in the CDR3 of the alpha chain that
      significantly influenced tumor cell recognition by human peripheral blood
      lymphocytes. One substitution, T for S at position 112 (S112T), enhanced tumor
      cell recognition by CD8(+) lymphocytes, and a second dually substituted receptor
      (S112T L110F) enhanced tumor cell recognition by CD4(+) T cells. CONCLUSIONS: The
      modified CEA-reactive TCRs are good candidates for future gene therapy clinical
      trials and show the power of selected amino acid substitutions in the antigen
      binding regions of the TCR to enhance desired reactivities.

PMID- 19118045
TI  - Polymeric tubulysin-peptide nanoparticles with potent antitumor activity.
AB  - PURPOSE: Tubulysins are naturally occurring tetrapeptides with potent
      antiproliferative activity against multiple cancer cell lines. However, they are
      also highly toxic in animal models. In order to improve the therapeutic index of
      this class of compounds, a nanoparticle prodrug of tubulysin A (TubA) was
      synthesized and evaluated in vitro and in vivo. EXPERIMENTAL DESIGN: A thiol
      derivative of TubA was covalently attached to a linear, beta-cyclodextrin based
      polymer through a disulfide linker (CDP-TubA). The polymer conjugate assembled
      into stable nanoparticles. Inhibition of tubulin polymerization and
      antiproliferative activity of the polymer conjugate were evaluated in vitro. The
      preclinical efficacy of CDP-TubA administered i.v. was evaluated in nude mice
      bearing s.c. implanted human HT29 colorectal and H460 non-small cell lung
      carcinoma tumors. RESULTS: The IC(50) of CDP-TubA (in Tub A equivalents) was 24,
      5, and 10 nmol/L versus 3, 1, and 2 nmol/L for Tub A in NCI-H1299 (lung), HT-29
      (colon), and A2780 (ovarian) cell lines, respectively. Tub A and the active thiol
      derivative were potent inhibitors of tubulin polymerization, whereas CDP-TubA
      showed minimal inhibition, indicating that target inhibition requires release of
      the peptide drug from the nanoparticles. The maximum tolerated dose of CDP-TubA
      was 6 mg/kg (in TubA equivalents) versus 0.05 mg/kg for TubA in nude mice. In
      vivo, a single treatment cycle of three weekly doses of CDP-TubA showed a potent
      antitumor effect and significantly prolonged survival compared with TubA alone.
      CONCLUSIONS: Cyclodextrin polymerized nanoparticles are an enabling technology
      for the safe and effective delivery of tubulysins for the treatment of cancer.

PMID- 19118046
TI  - RRR-alpha-vitamin E succinate potentiates the antitumor effect of calcitriol in
      prostate cancer without overt side effects.
AB  - PURPOSE: To determine the antitumor efficacy of using calcitriol combined with
      RRR-alpha-vitamin E succinate (VES) on prostate cancer. EXPERIMENTAL DESIGN: The
      effects of VES or VES in combination with calcitriol on the calcitriol target
      genes were evaluated by Western blot and real-time PCR. The antiproliferation
      effect of the combination in prostate cancer cells was evaluated by the
      combination index method. The role of the vitamin D(3) receptor (VDR) in the
      enhanced antitumor effects of the combination was confirmed by small interfering
      RNA knockdown strategy. Xenograft-bearing mice were used to reaffirm the
      antitumor efficacy of this combination. Pathohistology analyses and expressions
      of VDR and its target genes were analyzed in untreated and treated tumors.
      RESULTS: VES selectively increased VDR protein in different prostate cancer
      cells. Low doses of calcitriol combined with VES were significantly superior to
      the additive effect of individual treatments against prostate cancer cell
      proliferation. The expression of VDR target genes involved in antiproliferation
      were further sensitized in the presence of VES. Knockdown of VDR expression
      abolished the combination benefits in LNCaP and PC3 cells. Consistently, in
      prostate cancer xenograft models, VES enhanced the therapeutic efficacy of a
      tolerated dose of calcitriol yet without overt evidence of systemic toxicity and
      hypercalcemia. This notable in vivo effect was also accompanied by up-regulation
      of VDR target genes. CONCLUSIONS: Low-dose calcitriol combined with vitamin E
      analogue could be a solution to the calcemic side effect. The demonstration of
      superior antitumor activity of low-dose calcitriol plus VES provides the
      preclinical basis for developing a useful therapeutic strategy for prostate
      cancer.

PMID- 19118047
TI  - Tissue specific cytotoxicity of colon cancer cells mediated by nanoparticle
      delivered suicide gene in vitro and in vivo.
AB  - PURPOSE: This study aimed to develop an efficient and safe strategy to introduce
      suicide genes into colon cancer cells. EXPERIMENTAL DESIGN: In this study, we
      fused an enhanced carcinoembryonic antigen promoter (CEA) to a suicide gene,
      cytosine deaminase (CD). This construct was delivered into colon cancer cells
      using calcium phosphate nanoparticles (CPNP). The cells were then treated with
      the prodrug 5-FC. The therapeutic effect was evaluated in vitro and in vivo.
      RESULTS: Our study showed that the CEA promoter-driven, CPNP-delivered suicide
      gene was only expressed in CEA-positive colon cancer cells, and resulted in
      significant cytotoxicity after administration of the prodrug 5-FC in vitro.
      Moreover, our in vivo study showed that CPNP-mediated CEA-CD delivery, together
      with 5-FC treatment, resulted in significant tumor growth delay in xenograft
      human colon carcinoma. CONCLUSIONS: Our study indicates that the combination of
      CPNP and CEA-CD gene expression represents a novel approach for CEA-positive
      tumor gene therapy.

PMID- 19118048
TI  - rNAPc2 inhibits colorectal cancer in mice through tissue factor.
AB  - PURPOSE: Recombinant nematode anticoagulant protein c2 (rNAPc2) is a specific
      inhibitor of tissue factor (TF)/factor VIIa complex with novel antithrombotic
      activity. TF is highly expressed in human colorectal tumors, and levels are
      positively correlated with disease progression. EXPERIMENTAL DESIGN: To explore
      the therapeutic potential and mechanism of action of rNAPc2 during tumor growth
      and metastasis, we tested rNAPc2 in several experimental colorectal cancer models
      in mice. RESULTS: Administration of rNAPc2 inhibited pulmonary metastasis in mice
      systemically disseminated with CT26 murine colon carcinoma cells in a dose
      dependent fashion. Combining rNAPc2 with the cytotoxic agent 5-fluorouracil or
      bevacizumab (humanized anti-vascular endothelial growth factor monoclonal
      antibody) resulted in additive growth inhibition and simultaneous reduction of
      microvessel density in HCT116 human colorectal tumor xenografts in nude mice.
      Furthermore, rNAPc2 potentiated CPT-11 in inhibiting hepatic metastasis in nude
      mice with portal vein injection of HCT116 tumor cells. Long-term administration
      of rNAPc2 significantly suppressed spontaneous formation of intestinal tumors in
      Apc(Min/+) mice. Using a RNA interference approach, we showed that TF expression
      is necessary for rNAPc2-mediated inhibition of HCT116 human colorectal tumor
      xenograft growth in nude mice, indicating that the antitumor effect of rNAPc2 may
      be transduced through TF that is expressed on tumor cells. CONCLUSIONS: rNAPc2 is
      a potent anticancer agent when used in combination with chemotherapy or
      antiangiogenic therapy in mouse models of colorectal cancer, and TF positivity
      appears to be required for its activity.

PMID- 19118049
TI  - Mechanism and management of AKT inhibitor-induced hyperglycemia.
AB  - PURPOSE: Insulin-like growth factor-I receptor and phosphoinositide 3
      kinase/AKT/mammalian target of rapamycin pathways are among the most active areas
      of drug discovery in cancer research. However, due to their integral roles in
      insulin signaling, inhibitors targeting these pathways often lead to
      hyperglycemia and hyperinsulinemia. We investigated the mechanism of
      hyperglycemia induced by GSK690693, a pan-AKT kinase inhibitor in clinical
      development, as well as methods to ameliorate these side effects. EXPERIMENTAL
      DESIGN: The effect of GSK690693 on blood glucose, insulin, and glucagon levels
      was characterized in mice. We then evaluated the effects of commonly prescribed
      antidiabetic agents on GSK690693-induced hyperglycemia. The mechanism of blood
      glucose increase was evaluated using fasting and tracer uptake studies and by
      measuring liver glycogen levels. Finally, approaches to manage AKT inhibitor
      induced hyperglycemia were designed using fasting and low carbohydrate diet.
      RESULTS: We report that treatment with antidiabetic agents does not significantly
      affect GSK690693-induced hyperglycemia in rodents. However, administration of
      GSK690693 in mice significantly reduces liver glycogen (approximately 90%),
      suggesting that GSK690693 may inhibit glycogen synthesis and/or activate
      glycogenolysis. Consistent with this observation, fasting before drug
      administration reduces baseline liver glycogen levels and attenuates
      hyperglycemia. Further, GSK690693 also inhibits peripheral glucose uptake and
      introduction of a low-carbohydrate (7%) or 0% carbohydrate diet after GSK690693
      administration effectively reduces diet-induced hyperglycemia in mice.
      CONCLUSIONS: The mechanism of GSK690693-induced hyperglycemia is related to
      peripheral insulin resistance, increased gluconeogenesis, and/or hepatic
      glycogenolysis. A combination of fasting and low carbohydrate diet can reduce the
      magnitude of hyperglycemia induced by an AKT inhibitor.

PMID- 19118050
TI  - BMS-536924 reverses IGF-IR-induced transformation of mammary epithelial cells and
      causes growth inhibition and polarization of MCF7 cells.
AB  - PURPOSE: This study aimed to test the ability of a new insulin-like growth factor
      receptor (IGF-IR) tyrosine kinase inhibitor, BMS-536924, to reverse the ability
      of constitutively active IGF-IR (CD8-IGF-IR) to transform MCF10A cells, and to
      examine the effect of the inhibitor on a range of human breast cancer cell lines.
      EXPERIMENTAL DESIGN: CD8-IGF-IR-MCF10A cells were grown in monolayer culture,
      three-dimensional (3D) culture, and as xenografts, and treated with BMS-536924.
      Proliferation, cell cycle, polarity, and apoptosis were measured. Twenty-three
      human breast cancer cell lines were treated in monolayer culture with BMS-536924,
      and cell viability was measured. MCF7, MDA-MB-231, and MDA-MB-435 were treated
      with BMS-536924 in monolayer and 3D culture, and proliferation, migration,
      polarity, and apoptosis were measured. RESULTS: Treatment of CD8-IGF-IR-MCF10A
      cells grown in 3D culture with BMS-536924 caused a blockade of proliferation,
      restoration of apical-basal polarity, and enhanced apoptosis, resulting in a
      partial phenotypic reversion to normal acini. In monolayer culture, BMS-536924
      induced a dose-dependent inhibition of proliferation, with an accumulation of
      cells in G(0)/G(1,), and completely blocked CD8-IGF-IR-induced migration,
      invasion, and anchorage-independent growth. CD8-IGF-IR-MCF10A xenografts treated
      with BMS-536924 (100 mg/kg/day) showed a 76% reduction in xenograft volume. In a
      series of 23 human breast cancer cell lines, BMS-536924 inhibited monolayer
      proliferation of 16 cell lines. Most strikingly, treatment of MCF7 cells grown in
      3D culture with BMS-536924 caused blockade of proliferation, and resulted in the
      formation of hollow polarized lumen. CONCLUSIONS: These results show that the new
      small molecule BMS-536924 is an effective inhibitor of IGF-IR, causing a
      reversion of an IGF-IR - mediated transformed phenotype.

PMID- 19118051
TI  - Advancing bioluminescence imaging technology for the evaluation of anticancer
      agents in the MDA-MB-435-HAL-Luc mammary fat pad and subrenal capsule tumor
      models.
AB  - PURPOSE: Tumors grafted s.c. or under the mammary fat pad (MFP) rarely develop
      efficient metastasis. By applying bioluminescence imaging (BLI) technology, the
      MDA-MB-435-HAL-Luc subrenal capsule (SRC) model was compared with the MFP model
      for disease progression, metastatic potential, and response to therapy.
      EXPERIMENTAL DESIGN: The luciferase-expressing MDA-MB-435-HAL-Luc cell line was
      used in both MFP and SRC models. BLI technology allowed longitudinal assessment
      of disease progression and the therapeutic response to PD-0332991, Avastin, and
      docetaxel. Immunohistochemical analysis of Ki67 and CD31 staining in the primary
      tumors was compared in these models. Caliper measurement was used in the MFP
      model to validate the BLI quantification of primary tumors. RESULTS: The primary
      tumors in MDA-MB-435-HAL-Luc MFP and SRC models displayed comparable growth rates
      and vascularity. However, tumor-bearing mice in the SRC model developed lung
      metastases much earlier (4 weeks) than in the MFP model (>7 weeks), and the
      metastatic progression contributed significantly to the survival time. In the MFP
      model, BLI and caliper measurements were comparable for quantifying palpable
      tumors, but BLI offered an advantage for detecting the primary tumors that fell
      below a palpable threshold and for visualizing metastases. In the SRC model, BLI
      allowed longitudinal assessment of the antitumor and antimetastatic effects of PD
      0332991, Avastin, and docetaxel, and the results correlated with the survival
      benefits of these agents. CONCLUSIONS: The MDA-MB-435-HAL-Luc SRC model and the
      MFP model displayed differences in disease progression. BLI is an innovative
      approach for developing animal models and creates opportunities for improving
      preclinical evaluations of anticancer agents.

PMID- 19118052
TI  - Imaging intratumoral convection: pressure-dependent enhancement in
      chemotherapeutic delivery to solid tumors.
AB  - PURPOSE: Low-molecular weight (LMW) chemotherapeutics are believed to reach
      tumors through diffusion across capillary beds as well as membrane transporters.
      Unexpectedly, the delivery of these agents seems to be augmented by reductions in
      tumor interstitial fluid pressure, an effect typically associated with high
      molecular weight molecules that reach tumors principally through convection. We
      investigated the hypothesis that improved intratumoral convection can alter tumor
      metabolism and enhance the delivery of a LMW chemotherapeutic agent to solid
      tumors. EXPERIMENTAL DESIGN: For this purpose, we applied 31P/19F magnetic
      resonance spectroscopy (MRS) and magnetic resonance spectroscopic imaging (MRSI)
      to examine the influence of type I collagenase on tumor bioenergetics and the
      delivery of 5-fluorouracil (5FU) to HT29 human colorectal tumors grown s.c. in
      mice. RESULTS: Collagenase effected a 34% reduction in tumor interstitial fluid
      pressure with an attendant disintegration of intratumoral collagen. Neither mice
      administered collagenase nor controls receiving PBS showed changes in
      (31)phosphorus MRS-measured tumor bioenergetics; however, a time-dependent
      increase in the content of extracellular inorganic phosphate (Pi(e)) was observed
      in tumors of collagenase-treated animals. (31)Phosphorus MRSI showed that this
      increase underscored a more homogeneous distribution of Pi(e) in tumors of
      experimental mice. (19)Fluorine MRS showed that these changes were associated
      with a 50% increase in 5FU uptake in tumors of experimental versus control
      animals; however, this increase resulted in an increase in 5FU catabolites rather
      than fluoronucleotide intermediates that are required for subsequent
      cytotoxicity. CONCLUSIONS: These data indicate that the modulation of convective
      flow within tumors can improve the delivery of (LMW) chemotherapeutics and show
      the potential role for noninvasive imaging of this process in vivo.

PMID- 19118053
TI  - Involvement of epithelial cell transforming sequence-2 oncoantigen in lung and
      esophageal cancer progression.
AB  - PURPOSE: This study aims to isolate potential molecular targets for diagnosis,
      treatment, and/or prevention of lung and esophageal carcinomas. EXPERIMENTAL
      DESIGN: We screened for genes that were frequently overexpressed in the tumors
      through gene expression profile analyses of 101 lung cancers and 19 esophageal
      squamous cell carcinomas (ESCC) by cDNA microarray consisting of 27,648 genes or
      expressed sequence tags. In this process, we identified epithelial cell
      transforming sequence 2 (ECT2) as a candidate. Tumor tissue microarray was
      applied to examine the expression of ECT2 protein in 242 archived non-small-cell
      lung cancers (NSCLC) and 240 ESCC specimens and to investigate its prognostic
      value. A role of ECT2 in lung and esophageal cancer cell growth and/or survival
      was examined by small interfering RNA experiments. Cellular invasive activity of
      ECT2 in mammalian cells was examined using Matrigel assays. RESULTS: Northern
      blot and immunohistochemical analyses detected expression of ECT2 only in testis
      among 23 normal tissues. Immunohistochemical staining showed that a high level of
      ECT2 expression was associated with poor prognosis for patients with NSCLC (P =
      0.0004) as well as ESCC (P = 0.0088). Multivariate analysis indicated it to be an
      independent prognostic factor for NSCLC (P = 0.0005). Knockdown of ECT2
      expression by small interfering RNAs effectively suppressed lung and esophageal
      cancer cell growth. In addition, induction of exogenous expression of ECT2 in
      mammalian cells promoted cellular invasive activity. CONCLUSIONS: ECT2 cancer
      testis antigen is likely to be a prognostic biomarker in clinic and a potential
      therapeutic target for the development of anticancer drugs and cancer vaccines
      for lung and esophageal cancers.

PMID- 19118054
TI  - Validation of a standardized method for enumerating circulating endothelial cells
      and progenitors: flow cytometry and molecular and ultrastructural analyses.
AB  - PURPOSE: Antigenic overlap among circulating endothelial cells (CEC) and
      progenitors (CEP), platelets, and other blood cells led to the need to develop a
      reliable standardized method for CEC and CEP quantification. These cells are
      emerging as promising preclinical/clinical tools to define optimal biological
      doses of antiangiogenic therapies and to help stratify patients in clinical
      trials. EXPERIMENTAL DESIGN: We report the experimental validation of a novel
      flow cytometry method that precisely dissects CEC/CEP from platelets and other
      cell populations and provides information about CEC/CEP viability. RESULTS:
      Sorted DNA/Syto16(+)CD45(-)CD31(+)CD146(+) CECs, investigated by electron
      microscopy, were found to be bona fide endothelial cells by the presence of
      Weibel-Palade bodies. More than 75% of the circulating mRNAs of the endothelial
      specific gene, VE-cadherin, found in the blood were present in the sorted
      population. CECs were 140 +/- 171/mL in healthy subjects (n = 37) and 951 +/-
      1,876/mL in cancer patients (n = 78; P < 0.0001). The fraction of
      apoptotic/necrotic CECs was 77 +/- 14% in healthy subjects and 43 +/- 23% in
      cancer patients (P < 0.0001). CEPs were 181 +/- 167/mL in healthy donors and 429
      +/- 507/mL in patients (P = 0.00019). Coefficients of variation were 4 +/- 4%
      (intrareader), 17 +/- 4% (interreader), and 17 +/- 7% (variability over 0-72 h),
      respectively. Parallel samples were frozen by a standardized protocol. After
      thawing, coefficients of variation were 12 +/- 8% (intrareader), 16 +/- 10%
      (interreader), and 26 +/- 16% (variability over 0-14 days of frozen storage),
      respectively. CONCLUSIONS: This procedure enumerates a truly endothelial cell
      population with limited intrareader and interreader variability. It appears
      possible to freeze samples for large-scale CEC enumeration during clinical
      trials. This approach could be enlarged to investigate other angiogenic cell
      populations as well.

PMID- 19118055
TI  - SCG3 transcript in peripheral blood is a prognostic biomarker for REST-deficient
      small cell lung cancer.
AB  - PURPOSE: Specific markers of circulating tumor cells may be informative in
      managing lung cancer. Because the RE-1 silencing transcription factor (REST/NRSF)
      is a transcriptional repressor that is inactivated in neuroendocrine lung cancer,
      we identified REST-regulated transcripts (CHGA, CHGB, SCG3, VGF, and PCSK1) for
      evaluation as biomarkers in peripheral blood. EXPERIMENTAL DESIGN: Transcripts
      were screened across lung cancer and normal cell lines. Candidates were assessed
      by reverse transcription-PCR and hybridization of RNA extracted from the
      peripheral blood of 111 lung cancer patients obtained at clinical presentation
      and from 27 cancer-free individuals. RESULTS: Expression profiling revealed
      multiple chromogranin transcripts were readily induced on REST depletion, most
      notably SCG3 was induced >500-fold. The SCG3 transcript was also overexpressed by
      12,000-fold in neuroendocrine compared with nonneuroendocrine lung cancer cells.
      In peripheral blood of lung cancer patients and cancer-free individuals, we found
      that SCG3 was more tumor-specific and more sensitive than other chromogranin
      transcripts as a biomarker of circulating tumor cells. Overall, 36% of small cell
      lung cancer (SCLC) and 16% of non-SCLC patients scored positively for normalized
      SCG3 transcript. This correlated with worse survival among SCLC patients with
      limited disease (n = 33; P = 0.022) but not extensive disease (n = 29; P =
      0.459). Interestingly, the subcohort of 6 SCLC patients with resistance to
      platinum/etoposide chemotherapy all scored positively for peripheral blood SCG3
      transcript (P = 0.022). CONCLUSIONS: SCG3 mRNA, a component of the REST-dependent
      neurosecretory transcriptional profile, provides a sensitive prognostic biomarker
      for noninvasive monitoring of neuroendocrine lung cancer.

PMID- 19118056
TI  - An immune response enriched 72-gene prognostic profile for early-stage non-small
      cell lung cancer.
AB  - PURPOSE: Current staging methods are imprecise for predicting prognosis of early
      stage non-small-cell lung cancer (NSCLC). We aimed to develop a gene expression
      profile for stage I and stage II NSCLC, allowing identification of patients with
      a high risk of disease recurrence within 2 to 3 years after initial diagnosis.
      EXPERIMENTAL DESIGN: We used whole-genome gene expression microarrays to analyze
      frozen tumor samples from 172 NSCLC patients (pT1-2, N0-1, M0) from five European
      institutions, who had undergone complete surgical resection. Median follow-up was
      89 months (range, 1.2-389) and 64 patients developed a recurrence. A random two
      thirds of the samples were assigned as the training cohort with the remaining
      samples set aside for independent validation. Cox proportional hazards models
      were used to evaluate the association between expression levels of individual
      genes and patient recurrence-free survival. A nearest mean analysis was used to
      develop a gene-expression classifier for disease recurrence. RESULTS: We have
      developed a 72-gene expression prognostic NSCLC classifier. Based on the
      classifier score, patients were classified as either high or low risk of disease
      recurrence. Patients classified as low risk showed a significantly better
      recurrence-free survival both in the training set (P < 0.001; n = 103) and in the
      independent validation set (P < 0.01; n = 69). Genes in our prognostic signature
      were strongly enriched for genes associated with immune response. CONCLUSIONS:
      Our 72-gene signature is closely associated with recurrence-free and overall
      survival in early-stage NSCLC patients and may become a tool for patient
      selection for adjuvant therapy.

PMID- 19118057
TI  - Cyclooxygenase-2 is an independent prognostic factor in gastric carcinoma
      patients receiving adjuvant chemotherapy and is not associated with EBV
      infection.
AB  - PURPOSE: Cyclooxygenase-2 (COX-2) is believed to be involved in carcinogenesis in
      patients with chronic gastritis with Helicobacter pylori infection. EBV is
      detected in approximately 10% of gastric carcinomas and H. pylori induces EBV
      reactivation in the gastric epithelium. We aimed to evaluate significance of COX
      2 in gastric carcinoma occurred in EBV and H. pylori prevalent area. EXPERIMENTAL
      DESIGN: Tissue microarray samples from 457 gastric carcinoma patients who
      underwent gastrectomy and adjuvant chemotherapy were studied with EBER1 in situ
      hybridization for EBV and immunohistochemistry for COX-2 and other gastric
      carcinoma-related proteins (hMLH1, E-cadherin, c-erbB, and cyclin D1). RESULTS:
      EBV infection was observed in 10.9% of gastric carcinomas and was associated with
      proximal tumor location, increased numbers of lymph node, and E-cadherin
      expression (P < 0.01). COX-2 overexpression was closely associated with
      intestinal histologic type and lower tumor stage (P = 0.01). Univariate analysis
      showed that pT, pN, lymph node ratio, American Joint Committee on Cancer stage,
      numbers of negative lymph nodes, and resection margin <1 cm were significant
      prognostic factors. The Cox proportional hazards regression analysis indicated
      that lack of COX-2 expression and resection margin <1 cm were independent
      prognostic factors for disease-free survival (P = 0.008 and 0.03, respectively)
      and overall survival (P = 0.01 and 0.007, respectively). CONCLUSIONS: EBV
      infection is not associated with COX-2 expression or survival in gastric
      carcinoma. Lack of COX-2 expression is an independent prognostic factor in both
      overall and disease-free survival in gastric carcinoma. Our results indicate that
      COX-2 may play a role in the progression of gastric carcinoma regardless of EBV
      infection and is closely associated with histologic differentiation and
      prognosis.

PMID- 19118058
TI  - HLA class I - associated immunodominance affects CTL responsiveness to an ESO
      recombinant protein tumor antigen vaccine.
AB  - PURPOSE: Vaccination with full-length human tumor antigens aims at inducing or
      increasing antitumor immune responses, including CD8 CTL in cancer patients
      across the HLA barrier. We have recently reported that vaccination with a
      recombinant tumor-specific NY-ESO-1 (ESO) protein, administered with Montanide
      and CpG resulted in the induction of specific integrated antibody and CD4 T cell
      responses in all vaccinated patients examined, and significant CTL responses in
      half of them. Vaccine-induced CTL mostly recognized a single immunodominant
      region (ESO 81-110). The purpose of the present study was to identify genetic
      factor(s) distinguishing CTL responders from nonresponders. EXPERIMENTAL DESIGN:
      We determined the HLA class I alleles expressed by CTL responders and
      nonresponders using high-resolution molecular typing. Using short overlapping
      peptides spanning the ESO immunodominant CTL region and HLA class I/ESO peptide
      tetramers, we determined the epitopes recognized by the majority of vaccine
      induced CTL. RESULTS: CTL induced by vaccination with ESO protein mostly
      recognized distinct but closely overlapping epitopes restricted by a few
      frequently expressed HLA-B35 and HLA-Cw3 alleles. All CTL responders expressed at
      least one of the identified alleles, whereas none of the nonresponders expressed
      them. CONCLUSIONS: Expression of HLA-B35 and HLA-Cw3 is associated with the
      induction of immunodominant CTL responses following vaccination with recombinant
      ESO protein. Because recombinant tumor-specific proteins are presently among the
      most promising candidate anticancer vaccines, our findings indicate that the
      monitoring of cancer vaccine trials should systematically include the assessment
      of HLA association with responsiveness.

PMID- 19118059
TI  - Nonpegylated liposomal doxorubicin (TLC-D99), paclitaxel, and trastuzumab in HER
      2-overexpressing breast cancer: a multicenter phase I/II study.
AB  - PURPOSE: To determine the recommended dose, cardiac safety, and antitumor
      activity of nonpegylated liposomal doxorubicin (TLC-D99), paclitaxel, and the
      anti-HER-2 monoclonal antibody trastuzumab in patients with HER-2-overexpressing
      locally advanced nonoperable breast cancer (LABC) and metastatic breast cancer
      (MBC). EXPERIMENTAL DESIGN: Women with measurable, previously untreated, HER-2
      overexpressing LABC and MBC with a baseline left ventricular ejection fraction
      (LVEF) >50% received weekly trastuzumab in combination with escalating doses of
      weekly paclitaxel and TLC-D99 every 3 weeks for 6 cycles. LVEF monitoring was
      done every 3 weeks for the first 18 weeks and every 8 weeks thereafter. RESULTS:
      Sixty-nine patients participated, 15 in the dose escalating part and 54 at the
      recommended phase II dose (28 patients with LABC and 26 patients with MBC). The
      recommended doses of TLC-D99 and paclitaxel were 50 mg/m(2) every 3 weeks and 80
      mg/m(2)/wk, respectively. Twelve (17%) patients developed asymptomatic declines
      in LVEF. In 8 of these patients, LVEF recovered to >or=50% after a median time of
      9 weeks (range, 3-38 weeks). In the rest of patients, LVEF ranged from 44% to
      49%. No patients developed symptomatic cardiac heart failure. The overall
      response rate was 98.1% (95% confidence interval, 90.1-99.9) with a median time
      to progression not reached in LABC and of 22.1 months (95% confidence interval,
      16.4-46.3) in MBC patients. CONCLUSIONS: Nonpegylated doxorubicin, paclitaxel,
      and trastuzumab combination is safe, does not result in clinically manifest
      cardiac toxicity, and has a high rate of durable responses in HER-2
      overexpressing breast cancer patients. Further exploration of this combination is
      warranted.

PMID- 19118060
TI  - DNA methylation markers predict outcome in node-positive, estrogen receptor
      positive breast cancer with adjuvant anthracycline-based chemotherapy.
AB  - PURPOSE: We have shown that DNA methylation of the PITX2 gene predicts risk of
      distant recurrence in steroid hormone receptor-positive, node-negative breast
      cancer. Here, we present results from a multicenter study investigating whether
      PITX2 and other candidate DNA methylation markers predict outcome in node
      positive, estrogen receptor-positive, HER-2-negative breast cancer patients who
      received adjuvant anthracycline-based chemotherapy. EXPERIMENTAL DESIGN: Using a
      microarray platform, we analyzed DNA methylation in regulatory regions of PITX2
      and 60 additional candidate genes in 241 breast cancer specimens. Using Cox
      regression analysis, we assessed the predictive power of the individual
      marker/marker panel candidates. Clinical endpoints were time to distant
      metastasis, disease-free survival, and overall survival. A nested bootstrap/cross
      validation strategy was applied to identify and validate marker panels. RESULTS:
      DNA methylation of PITX2 and 14 other genes was correlated with clinical outcome.
      In multivariate models, each methylation marker added significant information to
      established clinical factors. A four-marker panel including PITX2, BMP4, FGF4,
      and C20orf55 was identified that resulted in improvement of outcome prediction
      compared with PITX2 alone. CONCLUSIONS: This study provides further evidence for
      the PITX2 biomarker, which has now been successfully confirmed to predict outcome
      among different breast cancer patient populations. We further identify new DNA
      methylation biomarkers, three of which can be combined into a panel with PITX2 to
      increase the outcome prediction performance in our anthracycline-treated primary
      breast cancer population. Our results show that a well-defined panel of DNA
      methylation markers enables outcome prediction in lymph node-positive, HER-2
      negative breast cancer patients treated with anthracycline-based chemotherapy.

PMID- 19118061
TI  - Overexpression of the KIT/SCF in uveal melanoma does not translate into clinical
      efficacy of imatinib mesylate.
AB  - PURPOSE: Recently, gene amplification and overexpression of KIT as well as
      activating mutations in the KIT gene have been described to occur in certain
      subsets of melanoma. These findings suggest KIT as a potential target for therapy
      with imatinib mesylate in these melanomas. To date, data on the KIT status in
      uveal melanoma (UM) is limited. EXPERIMENTAL DESIGN: We analyzed the expression
      of the KIT protein (CD117, c-kit) and its ligand, stem cell factor (SCF), in
      primary and metastatic UM. RESULTS: By immunohistochemistry, SCF-positive tumor
      cells (>90%) were detectable in 43% of primary UM and in 58% of UM metastases.
      Strong expression of KIT (>90%) in tumor cells was present in 55% of primary UM
      and in 76% of UM metastases. This overexpression of both KIT and SCF suggests the
      clinical application of imatinib mesylate in metastatic UM. This notion was
      tested in a clinical study using Simon's two-stage design. Patients received
      imatinib (600 mg p.o. daily) until progress or unacceptable toxicities. The trial
      did not enter stage II as no objective response was observed in the first group.
      This observation prompted further molecular analysis, which revealed no mutations
      in the genomic sequence of KIT in exons 11, 13, 17, and 18. Moreover, the mitogen
      activated protein kinase pathway was not activated in any of the tumors as
      measured by ERK phosphorylation. CONCLUSIONS: These results show the lack of
      clinical effectiveness of imatinib in UM, which was originally anticipated based
      on the high levels of KIT and SCF expression.

PMID- 19118062
TI  - Phase II study of protracted daily temozolomide for low-grade gliomas in adults.
AB  - PURPOSE: Resistance to temozolomide chemotherapy is partly mediated by O(6)
      methylguanine-DNA methlytransferase (MGMT). Protracted treatment with
      temozolomide potentially overcomes MGMT resistance and improves outcome. We
      conducted a phase II study of protracted daily temozolomide in adults with low
      grade gliomas. EXPERIMENTAL DESIGN: Patients with newly diagnosed
      oligodendroglioma or oligoastrocytoma with a MIB-1 index of >5% or recurrent low
      grade gliomas received temozolomide (75 mg/m(2)/day in 11-week cycles of 7 weeks
      on/4 weeks off). Treatment continued for a total of six cycles or until tumor
      progression or unacceptable toxicity. Primary end point was best overall response
      rate; secondary end points were progression-free survival, overall survival, and
      toxicity. We correlated response with MGMT promoter methylation and chromosome
      1p/19q deletion status. RESULTS: Forty-four patients were treated (14 female, 30
      male) with a median follow-up of 39.4 months. Median age was 43 years (range, 20
      68 years) and median Karnofsky performance status was 90 (range, 70-100). The
      regimen was well tolerated. No patients had a complete response (0%), 9 had
      partial response (20%), 33 had stable disease (75%), and 2 had progressive
      disease (5%). A total of 21 patients eventually progressed with an overall median
      progression-free survival of 38 months. Patients with methylated MGMT promoter
      had a longer overall survival (P = 0.008). Deletion of either 1p or 19q
      chromosomes also predicted longer overall survival (hazard ratio, 0.17; 95%
      confidence interval, 0.03-0.93; log-rank P = 0.02). CONCLUSIONS: A protracted
      course of daily temozolomide is a well-tolerated regimen and seems to produce
      effective tumor control. This compares favorably with historical data on the
      standard 5-day temozolomide regimen.

PMID- 19118064
TI  - Population pharmacokinetic/pharmacodynamic analyses of pemetrexed and
      neutropenia: effect of vitamin supplementation and differences between Japanese
      and Western patients.
AB  - PURPOSE: The objectives of the analysis were to characterize the time course of
      neutropenia after pemetrexed administration using an established semimechanistic
      physiologic model, characterize the relationship between pemetrexed exposure and
      neutropenia, and describe differences in neutropenic response by vitamin
      supplementation status and between Japanese and Western patients. EXPERIMENTAL
      DESIGN: An eight-compartment population pharmacokinetic/pharmacodynamic model was
      used to describe the absolute neutrophil count (ANC)-time profile (neutropenic
      response) following pemetrexed doses of 300 to 1,400 mg/m(2) administered every
      21 days. The analyses pooled data from 13 studies including 279 patients (161
      supplemented with oral folic acid and intramuscular vitamin B(12), and 118
      unsupplemented; 248 Western and 31 Japanese) who received 857 treatment cycles.
      RESULTS: Vitamin supplementation status, ethnic origin, and drug exposure were
      the dominant predictors of neutropenic response. Vitamin supplementation
      diminishes neutropenic response to pemetrexed. Model-predicted ANC nadirs for the
      "typical" Western patient receiving 500 mg/m(2) pemetrexed +/- vitamin
      supplementation were 2.74 x 10(9)/L and 1.70 x 10(9)/L, respectively. Japanese
      patients had a less pronounced neutropenic response to pemetrexed relative to
      Western patients. The model-predicted ANC nadir for Japanese patients receiving
      500 mg/m(2) pemetrexed with vitamin supplementation was 2.66 x 10(9)/L. Values
      for the 1,000 mg/m(2) dose with vitamin supplementation were 1.91 x 10(9)/L and
      1.34 x 10(9)/L for Japanese and Western patients, respectively. Increased
      albumin, decreased cystathionine, and decreased body surface area were also
      associated with increased neutropenic response. CONCLUSIONS: The neutropenic
      response to higher pemetrexed doses administered with vitamin supplementation is
      tolerable. All other factors equal, Japanese patients have a lesser neutropenic
      response to pemetrexed relative to Western patients.

PMID- 19118063
TI  - O6-methylguanine DNA methyltransferase deficiency and response to temozolomide
      based therapy in patients with neuroendocrine tumors.
AB  - PURPOSE: Recent studies suggest that temozolomide has activity in neuroendocrine
      tumors. Low levels of the DNA repair enzyme, O(6)-methylguanine DNA
      methyltransferase (MGMT), are associated with sensitivity to temozolomide in
      other tumor types. We evaluated the prevalence of MGMT deficiency in
      neuroendocrine tumors and correlated MGMT deficiency with treatment response to
      temozolomide-based regimens. EXPERIMENTAL DESIGN: The prevalence of MGMT
      deficiency, measured by immunohistochemistry, was assessed in 97 archival
      neuroendocrine tumor specimens. Rates of treatment response and survival were
      next evaluated in a cohort of 101 consecutive neuroendocrine tumor patients who
      had received treatment with a temozolomide-based regimen at one of three
      institutions. MGMT expression was directly correlated with treatment response in
      21 patients who had available tumor tissue and response data. RESULTS: In
      archival specimens, MGMT deficiency was observed in 19 of 37 (51%) pancreatic
      neuroendocrine tumors and 0 of 60 (0%) carcinoid tumors (P < 0.0001). In the
      clinical cohort, 18 of 53 (34%) patients with pancreatic neuroendocrine tumors
      but only 1 of 44 (2%) patients with carcinoid tumors (P < 0.001) experienced a
      partial or complete response to temozolomide-based therapy. Among 21 patients
      with evaluable tumor tissue who had also received treatment with temozolomide, 4
      of 5 patients with MGMT-deficient tumors (all pancreatic neuroendocrine tumors)
      and 0 of 16 patients with tumors showing intact MGMT expression responded to
      treatment (P = 0.001). CONCLUSIONS: MGMT deficiency, measured by
      immunohistochemistry, is more common in pancreatic neuroendocrine tumors than in
      carcinoid tumors as is treatment response to temozolomide-based therapy. Absence
      of MGMT may explain the sensitivity of some pancreatic neuroendocrine tumors to
      treatment.

PMID- 19118065
TI  - Lenalidomide and rituximab in Waldenstrom's macroglobulinemia.
AB  - PURPOSE: Thalidomide and its more potent immunomodulatory derivative lenalidomide
      enhance rituximab-mediated antibody-dependent cell-mediated cytotoxicity. We
      therefore evaluated lenalidomide and rituximab in symptomatic Waldenstrom's
      macroglobulinemia (WM) patients naive to either agent. EXPERIMENTAL DESIGN:
      Intended therapy consisted of 48 weeks of lenalidomide (25 mg/d for 3 weeks and
      then 1 week off) along with rituximab (375 mg/m(2)/wk) dosed on weeks 2 to 5 and
      13 to 16. Sixteen patients were enrolled, 12 of whom were previously untreated.
      RESULTS: Unexpectedly, we observed an acute decrease in hematocrit in 13 of 16
      patients (median hematocrit decrease, 4.8%), which was attributable to
      lenalidomide patients and which led to cessation of further enrollment on this
      study. Lenalidomide-related anemia was observed even at doses as low as 5 mg/d
      and occurred in the absence of hemolysis or other cytopenias. The overall
      response and major response (<50% decrease in serum IgM) rates were 50% and 25%,
      respectively, on an intent-to-treat basis. With a median follow-up of 31.3
      months, 4 of 8 responding patients have progressed with a median time to
      progression of 18.9 months. CONCLUSION: Lenalidomide produces unexpected but
      clinically significant acute anemia in patients with WM. In comparison with our
      previous study with thalidomide and rituximab in an analogous patient population,
      the responses achieved in WM patients with lenalidomide and rituximab appear less
      favorable.

PMID- 19118067
TI  - Alemtuzumab therapy for hypereosinophilic syndrome and chronic eosinophilic
      leukemia.
AB  - PURPOSE: Patients with hypereosinophilic syndrome (HES) or chronic eosinophilic
      leukemia (CEL) that are refractory to standard therapies are difficult to manage
      and have significantly shortened life expectancy. EXPERIMENTAL DESIGN: CD52 is a
      surface glycoprotein highly expressed on eosinophils. We treated 11 patients with
      advanced HES/CEL with alemtuzumab, a humanized anti-CD52 monoclonal antibody.
      Alemtuzumab was administered, in general, first in escalating doses (5, 10, 30 mg
      i.v. on days 1-3), then at the tolerated dose thrice per week for a total of 12
      doses. Patients with complete hematologic response (CHR; normal percent and
      absolute eosinophil count) were allowed to continue therapy once weekly as
      maintenance. RESULTS: Ten patients (91%) achieved CHR after a median of 2 weeks
      (0.5-5 weeks) of therapy. Bone marrow eosinophilia resolved in four of seven
      evaluable patients. The median duration of CHR was 3 months (1.5-17+ months).
      Seven of the 10 CHR patients relapsed, five while off-therapy. Two patients
      achieved second CHR upon alemtuzumab rechallenge. Three patients experienced mild
      infusion-related symptoms, two developed cytomegalovirus reactivation requiring
      therapy, and one developed orbital lymphoma that was successfully treated.
      CONCLUSIONS: Our limited experience suggests alemtuzumab to be a valuable therapy
      for advanced HES or CEL, refractory to standard therapies, and supports the
      clinical evaluation of alemtuzumab in a larger trial.

PMID- 19118066
TI  - A phase I trial of a human papillomavirus DNA vaccine for HPV16+ cervical
      intraepithelial neoplasia 2/3.
AB  - PURPOSE: To evaluate the safety and immunogenicity of a therapeutic human
      papillomavirus (HPV)16 DNA vaccine administered to women with HPV16+cervical
      intraepithelial neoplasia (CIN)2/3. EXPERIMENTAL DESIGN: This phase I trial
      incorporated the standard '3+3'' dose-escalation design with an additional 6
      patients allocated to the maximally tolerated dose. Healthy adult women with
      colposcopically directed, biopsy-proven HPV16+ CIN2/3 received 3 i.m.
      vaccinations (0.5, 1, or 3 mg) of a plasmid expressing a Sig-E7(detox)-heat shock
      protein 70 fusion protein on days 0, 28, and 56, and underwent standard
      therapeutic resection of the cervical squamocolumnar junction at day 105 (week
      15). The safety and immunogenicity of the vaccine and histologic outcome based on
      resection at week 15 were assessed. RESULTS: Fifteen patients were evaluable (3
      each at 0.5 and 1mg, 9 at 3 mg). The vaccine was well tolerated: most adverse
      events were mild, transient injection-site discomfort; no dose-limiting
      toxicities were observed. Although HPVE7-specific T-cell responses to E7 detected
      by enzyme-linked immunospot assays (IFN-gamma) were of low frequency and
      magnitude, detectable increases in response subsequent to vaccination were
      identified in subjects in the second and third cohorts. Complete histologic
      regression occurred in 3 of 9 (33%; 7-70% confidence interval) individuals in the
      highest-dose cohort. Although the difference is not significant, it is slightly
      higher than would be expected in an unvaccinated cohort (25%). CONCLUSIONS: This
      HPV16 DNA vaccine was safe and well tolerated. Whereas it seems possible to
      elicit HPV-specific T-cell responses in patients with established dysplastic
      lesions, other factors are likely to play a role in lesion regression.

PMID- 19118068
TI  - Phase I and pharmacokinetic study of gimatecan given orally once a week for 3 of
      4 weeks in patients with advanced solid tumors.
AB  - PURPOSE: A phase I study was conducted to determine the dose-limiting toxicities
      (DLT) and maximum tolerated dose (MTD) of gimatecan, a lipophilic camptothecin
      analogue, administered orally once a week for 3 weeks. EXPERIMENTAL DESIGN: Adult
      patients with advanced solid tumors with good performance status and adequate
      hematologic, hepatic, and renal function were eligible for the study. The plasma
      pharmacokinetics of the drug was characterized during the initial 28-day cycle.
      RESULTS: A total of 33 patients were evaluated at 7 dose levels ranging from 0.27
      to 3.20 mg/m(2)/wk. Anemia, fatigue, neutropenia, nausea, and vomiting were the
      principal toxicities. DLTs experienced by 3 of 7 patients in dose level 7 (3.20
      mg/m(2)) were grade 2 hyperbilirubinemia and grade 3 to 4 fatigue. DLT (anorexia
      and nausea) occurred in only 1 of 11 patients evaluated at the MTD of 2.40
      mg/m(2). There were no objective responses, although disease stabilization was
      observed in 4 patients. Gimatecan has a very long apparent biological half-life
      (mean +/- SD, 77 +/- 37 h) and exists in plasma almost entirely as the
      pharmacologically active intact lactone form. At the MTD, mean peak
      concentrations of the drug in plasma ranged from 67 to 82 ng/mL for the 3 weekly
      doses and the mean concentration 7 days after dosing was 15 +/- 18 ng/mL.
      CONCLUSIONS: Administration of gimatecan orally once a week at doses that are
      well tolerated provides continuous exposure to potentially effective plasma
      concentrations of the biologically active form of the drug. This regimen deserves
      further evaluation to define its antitumor activity in specific tumor types
      either alone or in combination with other agents.

PMID- 19118069
TI  - Phase I and pharmacokinetic study of pemetrexed plus cisplatin in chemonaive
      patients with locally advanced or metastatic malignant pleural mesothelioma or
      non-small cell lung cancer.
AB  - PURPOSE: Pemetrexed is approved as monotherapy and in combination with cisplatin.
      The established combination dose was identified before the addition of folic acid
      and vitamin B(12) to the treatment regimen. We evaluated the toxicity and
      pharmacokinetics (PK) of higher pemetrexed doses with cisplatin and vitamin
      supplementation. EXPERIMENTAL DESIGN: Patients with malignant pleural
      mesothelioma or non-small cell lung cancer received pemetrexed doses from 500 to
      900 mg/m(2) + 75 mg/m(2) cisplatin once every 21 days. Folic acid and vitamin
      B(12) were administered per label recommendations. RESULTS: Twenty-one patients
      received a combined total of 84 cycles. The maximum tolerated dose was 900
      mg/m(2) pemetrexed + 75 mg/m(2) cisplatin. Dose-limiting toxicities at this dose
      included grade 3 anemia, bronchopneumonia, and neutropenia, and 1 death from
      sepsis secondary to grade 4 febrile neutropenia, considered possibly related to
      study drugs. The recommended dose was 800 mg/m(2) pemetrexed + 75 mg/m(2)
      cisplatin. Pemetrexed PK were consistent across doses; pemetrexed did not seem to
      affect total or free platinum PK. CONCLUSIONS: Pemetrexed with vitamin
      supplementation was safe and well tolerated at higher doses than the currently
      established 500 mg/m(2) + 75 mg/m(2) cisplatin. Based on this study, the
      recommended dose would be 800 mg/m(2) pemetrexed + 75 mg/m(2) cisplatin. However,
      recent studies showed a lack of improved efficacy for 900 or 1,000 mg/m(2) single
      agent pemetrexed versus 500 mg/m(2) and a lack of PK/pharmacodynamic exposure
      response relationship for the pemetrexed/cisplatin combination across pemetrexed
      exposures corresponding to this dose range. Based on currently available
      evidence, we recommend retaining the established dose.

PMID- 19118070
TI  - Intratumoral immune cell infiltrates, FoxP3, and indoleamine 2,3-dioxygenase in
      patients with melanoma undergoing CTLA4 blockade.
AB  - PURPOSE: CTL-associated antigen 4 (CTLA4)-blocking monoclonal antibodies induce
      long-term regression of metastatic melanoma in some patients, but the exact
      mechanism is unknown. In this study, biopsies of selected accessible tumor
      lesions from patients treated with tremelimumab were examined to further
      elucidate the mechanism of its antitumor activity. EXPERIMENTAL DESIGN: Fifteen
      tumor biopsies from 7 patients who had been treated with tremelimumab (CP
      675,206) were collected. Samples were analyzed for melanoma markers, immune cell
      subset markers, the presence of the T regulatory-specific transcription factor
      FoxP3 and the immunosuppressive enzyme indoleamine 2,3-dioxygenase (IDO).
      RESULTS: Clinically responding lesions had diffuse intratumoral infiltrates of
      CD8(+) T cells that were markedly increased in cases where comparison with a
      baseline biopsy was available. Nonregressing lesions had sparse, patchy CD8(+)
      intratumoral infiltrates. Patients with regressing lesions had an increased
      frequency of CD8(+) cells with or without a concomitant increase in CD4(+) cells.
      Two of 3 responding patients with paired samples showed a slight increase in the
      number of FoxP3(+) cells in the postdosing biopsies. In patients with regressing
      lesions who had paired samples, the intensity of IDO staining in macrophages
      and/or melanoma cells showed no clear pattern of change postdosing. CONCLUSIONS:
      Administration of tremelimumab was associated with massive intratumoral
      infiltrates of CD8(+) CTLs in patients with regressing tumors but had varying
      effects on intratumoral infiltrates of CD4(+) and FoxP3(+) cells or intratumoral
      expression of IDO.

PMID- 19118071
TI  - Interactions of IL-12A and IL-12B polymorphisms on the risk of cervical cancer in
      Chinese women.
AB  - PURPOSE: Accumulative evidence suggests that interleukin-12 (IL-12) plays a
      central role in the Th1 responses and thus participates in the carcinogenesis of
      human papillomavirus-related cervical cancer. We hypothesized that potentially
      functional polymorphisms in IL12A and IL12B may individually and jointly
      contribute to cervical cancer risk. EXPERIMENTAL DESIGN: We genotyped IL12A
      rs568408 [3' untranslated region (UTR) G>A] and rs2243115 (5'UTR T>G) and IL12B
      rs3212227 (3'UTR A>C) in a hospital-based study of 404 cervical cancer cases and
      404 cancer-free controls. RESULTS: The IL12A rs568408 GA/AA and IL12B rs3212227
      AC/CC variant genotypes were associated with a significantly increased risk of
      cervical cancer [adjusted odds ratio, 1.43; 95% confidence interval (CI), 1.06
      1.93; and adjusted odds ratio, 1.30; 95% CI, 0.97-1.75, respectively], compared
      with their corresponding wild-type homozygotes. Moreover, a significant gene-gene
      interaction of these 2 loci were evident in the risk of cervical cancer, and
      subjects carrying variant genotypes of both loci had a 1.82-fold (95% CI, 1.28
      2.57) increased risk of cervical cancer. In the stratified analyses, the combined
      genetic effect was more pronounced in patients who had early-stage tumors or more
      parities. Subjects carrying rs568408 AG/AA and rs3212227 AC/CC genotypes and
      having >2 parities showed a 6.00-fold (95% CI, 2.86-12.56) elevated cervical
      cancer risk (P for multiplicative interaction = 0.046). CONCLUSION: These
      findings suggest that IL12A rs568408 and IL12B rs3212227 may individually and
      jointly contribute to the risk of cervical cancer and may modify cervical cancer
      risk associated with parity, but these data need further validation.

PMID- 19118072
TI  - Role of the N-acetyltransferase 2 detoxification system in thyroid cancer
      susceptibility.
AB  - PURPOSE: Genetic polymorphisms in genes encoding for enzymes involved in the
      biotransformation of carcinogens have been shown to be relevant as risk for
      cancer and may be of considerable importance from a public health point of view.
      Considering that N-acetyltransferase 2 (NAT2) polymorphisms modulate the response
      to ionizing radiation, the strongest risk factor recognized to cause
      differentiated thyroid cancer (DTC) thus far, we sought to determine the
      influence of NAT2 detoxification system on thyroid cancer susceptibility.
      EXPERIMENTAL DESIGN: We conducted a prospective case-control study, comparing 195
      patients presenting with DTC that were previously genotyped for GSTT1, GSTM1,
      GSTP1, and CYP1A1, comprising 164 papillary carcinomas and 31 follicular
      carcinomas, with 196 control individuals paired for gender, age, ethnicity, diet
      routine, lifetime occupational history, smoking history, general health
      conditions, and previous diseases. We used PCR-RFLP assays and the combination of
      6 variant alleles to define 18 NAT2 haplotypes that characterized slow,
      intermediate, or rapid phenotypes. RESULTS: A multivariate logistic regression
      analysis identified the presence of *12A and the absence of *12B, *13, *14B,
      *14D, *6A, and *7A NAT2 haplotypes as risk factors for DTC. The inheritance of a
      rapid acetylation phenotype doubled the risk for a papillary carcinoma (odds
      ratio, 2.024; 95% confidence interval, 1.252-3.272). We found no relationship
      between genotypes and clinical, pathologic, or laboratory features of patients or
      between genotypes and outcome. CONCLUSIONS: We showed that NAT2 genotypes and the
      NAT2 rapid acetylation phenotype are important susceptibility factors for DTC,
      suggesting that NAT2 detoxification system is involved in this tumor
      pathogenesis.

PMID- 19118074
TI  - Prediction of cancer relapse after prostatectomy: use the postoperative nomogram.

PMID- 19118076
TI  - Biomarkers and response to therapy in breast cancer.

PMID- 19118077
TI  - Dr. Ehrlich and Dr. Atomic: beauty vs. horror in science.

PMID- 19118078
TI  - Discovery in the lab: Plato's paradox and Delbruck's principle of limited
      sloppiness.

PMID- 19118079
TI  - Umbilicus as a fitness signal in humans.
AB  - Typically, mammalian umbilical cord forms a tiny, stable, and asymmetrical scar.
      In contrast, humans have a clearly visible umbilicus that changes with age and
      nutrients gathered. Based on this, I propose that umbilicus, together with the
      surrounding skin area, is an honest signal of individual vigour. More precisely,
      I suggest that the symmetry, shape, and position of umbilicus can be used to
      estimate the reproductive potential of fertile females, including risks of
      certain genetically and maternally inherited fetal anomalies. The idea is
      supported by a comparative study where symmetrical t-shaped and oval-shaped
      umbilici of fertile females were considered the most attractive. Further support
      comes from observations that abnormal velocity of umbilical cord has been
      associated with fetal brain development, diabetes, and other fitness-related
      properties with a strong genetically or maternally inherited component. In
      addition, umbilicus and the umbilical skin area may reveal nutrimental
      competitive ability, and need for social care in small children and pregnant
      females. The novel hypothesis explains why umbilicus has aesthetic value, and why
      umbilicus has had a distinctive role in different cultures. If further research
      confirms the signalling hypothesis, female umbilici may be routinely measured to
      detect risk pregnancies of several fetal abnormalities.

PMID- 19118080
TI  - Intramedullary nailing of clavicular midshaft fractures with the titanium elastic
      nail: problems and complications.
AB  - BACKGROUND: Intramedullary nailing of clavicular midshaft fractures using the
      titanium elastic nail has been described as a technically easy, minimally
      invasive operation with few complications and an early return to competitive
      sports. HYPOTHESIS: The results reported thus far have been positive. The
      titanium elastic nail is associated with multiple intraoperative and
      postoperative problems. STUDY DESIGN: Case series; Level of evidence, 4. METHODS:
      From April 2004 to March 2007, 34 patients at our institution were treated with
      intramedullary nailing. A standard titanium elastic nail was used in 19 cases and
      a titanium elastic nail with an end cap in 15 cases. The titanium elastic nail
      was inserted and advanced under fluoroscopic control. A short incision at the
      fracture site was made for open reduction if needed. Postoperatively, free range
      of motion was allowed. RESULTS: In 62% of patients, open reduction was necessary
      independent of fracture type, flattening of the titanium elastic nail, or
      transverse fragments. Operating time was 44 minutes (range, 10-105 minutes) and
      fluoroscopy time 9 minutes (range, 2-25 minutes). In 70% of patients, problems or
      complications occurred (7 medial perforations, 7 lateral penetrations, 1 titanium
      elastic nail breakage, 1 titanium elastic nail dislocation, 7 hardware
      irritations). The reoperation rate was 36%. Medial migration and pain were
      significantly reduced by using an end cap. CONCLUSION: Intramedullary nailing of
      clavicular midshaft fractures using the titanium elastic nail is a technically
      demanding operation with various complications in the postoperative phase. This
      study might explain why the implant has not yet achieved widespread application,
      despite the fact that other authors have reported good results. Amending the
      operative technique and postoperative treatment might improve the outcome in the
      future.

PMID- 19118081
TI  - Structural damage and chemical contaminants on reprocessed arthroscopic shaver
      blades.
AB  - BACKGROUND: In response to socioeconomic pressure to cut budgets in medicine,
      single-use surgical instruments are often reprocessed despite potential
      biological hazard. PURPOSE: To evaluate the quality and contaminants of
      reprocessed shaver blades. HYPOTHESIS: Reprocessed shaver blades have mechanical
      damage and chemical contamination. STUDY DESIGN: Controlled laboratory study.
      METHODS: Seven blades and 3 abraders were reprocessed 1 time or 3 times and then
      were assessed. In the first part of the study, structural damage on the blades
      after 3 reprocessings was compared to that after 1 reprocessing using optical
      microscopy. In the second part, surface damage was observed using optical
      microscopy and scanning electron microscopy; elemental and chemical analyses of
      contaminants found by the microscopy were performed using scanning electron
      microscopy/energy dispersive x-ray spectroscopy, scanning Auger microscopy, and
      Fourier transform infrared spectroscopy. RESULTS: Optical microscopic examination
      revealed abrasion on the surface of the inner blade and cracks on the inner tube
      after 1 reprocessing. These changes were more evident after 3 reprocessings.
      Scanning electron microscopy/energy dispersive x-ray spectroscopy of the inner
      cutter of the blade reprocessed once showed contaminants containing calcium,
      carbon, oxygen, and silicon, and Fourier transform infrared spectroscopy
      demonstrated biological protein consisting mainly of collagen, some type of
      salts, and polycarbonate used in plastic molding. Scanning electron
      microscopy/energy dispersive x-ray spectroscopy of the inner cutter of the
      reprocessed abrader revealed contaminants containing carbon, calcium,
      phosphorous, and oxygen, and Fourier transform infrared spectroscopy showed H2O,
      hydroxyapatite, and hydroxyl proteins. Scanning Auger microscopy showed that the
      tin-nickel plating on the moving blade and abrader was missing in some locations.
      CONCLUSION: This is the first study to evaluate both mechanical damage and
      chemical contaminants containing collagen, hydroxyapatite, and salts on the
      reprocessed arthroscopic shaver blades. CLINICAL RELEVANCE: Surgeons should keep
      in mind that mechanical damage and chemical contamination are found on
      reprocessed arthroscopic blades.

PMID- 19118082
TI  - Tension level during preconditioning influences hamstring tendon graft
      properties.
AB  - BACKGROUND: Hamstring tendon grafts used for anterior cruciate ligament
      reconstruction are preconditioned to reduce the influence of viscoelasticity on
      the stiffness and tension. HYPOTHESIS: Increasing the tension applied during
      preconditioning will decrease the loss of tension and stiffness due to
      viscoelasticity. STUDY DESIGN: Controlled laboratory study. METHODS: Six
      quadruple-strand hamstring tendon grafts were tested twice in vitro with 2
      tension levels applied during preconditioning. The grafts were preconditioned at
      80 N or 160 N, followed by 15 minutes of relaxation, and subsequently loaded to
      80 N to represent application of initial tension. After 5 minutes of relaxation,
      the tension was recorded and the stiffness was measured over 0.06 mm of
      displacement. The tension and stiffness measurements were repeated 3 hours later.
      The data were compared between the 2 preconditioning levels with a 2-way repeated
      measures analysis of variance. RESULTS: Graft tension and stiffness were
      significantly larger (P < .05) for 160 N during preconditioning. For 80 N, the
      average tension at 5 minutes and 3 hours was 40 N and 21 N, respectively,
      compared with 50 N and 30 N, respectively, for 160 N. For 80 N, the average
      stiffness at 5 minutes and 3 hours was 152 N/mm and 124 N/mm, respectively,
      compared with 173 N/mm and 146 N/mm, respectively, for 160 N. CONCLUSION:
      Increasing the tension applied to hamstring tendon grafts during preconditioning
      can decrease the postoperative loss of tension and stiffness due to
      viscoelasticity. CLINICAL RELEVANCE: The increased graft tension and stiffness
      could reduce postoperative knee laxity.

PMID- 19118083
TI  - Ketoconazole increases fingolimod blood levels in a drug interaction via CYP4F2
      inhibition.
AB  - The sphingosine-1-phosphate receptor modulator fingolimod is predominantly
      hydroxylated by cytochrome CYP4F2. In vitro experiments showed that ketoconazole
      significantly inhibited the oxidative metabolism of fingolimod by human liver
      microsomes and by recombinant CYP4F2. The authors used ketoconazole as a putative
      CYP4F2 inhibitor to quantify its influence on fingolimod pharmacokinetics in
      healthy subjects. In a 2-period, single-sequence, crossover study, 22 healthy
      subjects received a single 5-mg dose of fingolimod in period 1. In period 2,
      subjects received ketoconazole 200 mg twice daily for 9 days and a single 5-mg
      dose of fingolimod coadministered on the 4th day of ketoconazole treatment.
      Ketoconazole did not affect fingolimod t(max) or half-life, but there was a weak
      average increase in C(max) of 1.22-fold (90% confidence interval, 1.15-1.30). The
      AUC over the 5 days of ketoconazole coadministration increased 1.40-fold (1.31
      1.50), and the full AUC to infinity increased 1.71-fold (1.53-1.91). The AUC of
      the active metabolite fingolimod-phosphate was increased to a similar extent by
      1.67-fold (1.50-1.85). Ketoconazole predose plasma levels were not altered by
      fingolimod. The magnitude of this interaction suggests that a proactive dose
      reduction of fingolimod is not necessary when adding ketoconazole to a fingolimod
      regimen. The clinician, however, should be aware of this interaction and bear in
      mind the possibility of a fingolimod dose reduction based on clinical monitoring.

PMID- 19118084
TI  - Outbreak of Streptococcus pneumoniae serotype 1 pneumonia in a United Kingdom
      school.

PMID- 19118085
TI  - Google watches over flu.

PMID- 19118086
TI  - Apology sought for Australian doctor accused of involvement in UK bomb attacks.

PMID- 19118088
TI  - The complex role of fibrin in acute lung injury.

PMID- 19118089
TI  - Airway inflammatory cell responses to intra-amniotic lipopolysaccharide in a
      sheep model of chorioamnionitis.
AB  - Chorioamnionitis, a risk factor for bronchopulmonary dysplasia in preterm
      infants, causes an influx of inflammatory cells into the fetal lung. Using a
      fetal sheep model, we evaluated the time course of activation, functional
      maturity, and apoptosis of the leukocytes recruited to the fetal air spaces by
      lipopolysaccharide (LPS). Time-mated sheep were given intra-amniotic injections
      with 10 mg of Escherichia coli LPS or saline 2 or 7 days before preterm delivery
      at 124 days of gestation (term is 150 days). Both neutrophils and monocytes in
      bronchoalveolar lavage fluid (BALF) had activated NF-kappaB after 2- and 7-day
      LPS exposures. These neutrophils and monocytes expressed the activation factor
      CD11b and the maturation factor PU.1 at 2 days, and increased PU.1 expression was
      detected in macrophages at 7 days. Leukocyte oxidative burst activity was
      greatest at 7 days. BALF lipid peroxidation increased fivefold at 2 days, while
      protein carbonyls increased eightfold at 7 days. Nitrative stress was not
      detected in the BALF, but leukocytes in the lung expressed nitric oxide synthase
      (NOS)II (inducible NOS). BALF leukocytes expressed the antioxidant peroxiredoxin
      V. Lung glutathione peroxidase was also increased with LPS exposure. There was
      minimal apoptosis of airway and lung leukocytes assessed by caspase-3 activation.
      Intra-amniotic LPS recruits leukocytes to the fetal air space that have a
      persistent activation. These results have implications for the pathogenesis of
      lung inflammatory disorders in the preterm.

PMID- 19118091
TI  - Gene regulation in the adaptive process to hypoxia in lung epithelial cells.
AB  - Lung alveolar epithelial cells are normally very well oxygenated but may be
      exposed to hypoxia in many pathological conditions such as pulmonary edema, acute
      respiratory distress syndrome, chronic obstructive pulmonary diseases, or in some
      environmental conditions such ascent to high altitude. The ability of alveolar
      epithelial cells to cope with low oxygen tensions is crucial to maintain the
      structural and functional integrity of the alveolar epithelium. Alveolar
      epithelial cells appear to be remarkably tolerant to oxygen deprivation as they
      are able to maintain adequate cellular ATP content during prolonged hypoxic
      exposure when mitochondrial oxidative phosphorylation is limited. This property
      mostly relies on the ability of the cells to rapidly modify their gene expression
      program, stimulating the expression of genes involved in anaerobic energy supply
      and repressing expression of genes involved in some ATP-consuming cellular
      processes. This adaptive strategy of the cells is mostly, but not entirely,
      dependent on the expression of hypoxia-inducible factors (HIFs), known to be
      responsible for orchestrating a large number of hypoxia-sensitive genes. This
      review focuses on the role of HIF isoforms expressed in alveolar epithelial cells
      exposed to hypoxia and on the specific hypoxic gene regulation that takes place
      in alveolar epithelial cells either through HIF-dependent or -independent
      pathways.

PMID- 19118090
TI  - Modulation of PKCdelta signaling alters the shear stress-mediated increases in
      endothelial nitric oxide synthase transcription: role of STAT3.
AB  - We have previously shown that the regulation of endothelial nitric oxide synthase
      (eNOS) in endothelial cells isolated from fetal lamb under static conditions is
      positively regulated by PKCdelta. In this study, we explore the role of PKCdelta
      in regulating shear-induced upregulation of eNOS. We found that shear caused a
      decrease in PKCdelta activation. Modulation of PKCdelta before shear with a
      dominant negative mutant of PKCdelta (DN PKCdelta) or bryostatin (a known
      PKCdelta activator) demonstrated that PKCdelta inhibition potentiates the shear
      mediated increases in eNOS expression and activity, while PKCdelta activation
      inhibited these events. To gain insight into the mechanism by which PKCdelta
      inhibits shear-induced eNOS expression, we examined activation of STAT3, a known
      target for PKCdelta phosphorylation. We found that shear decreased the
      phosphorylation of STAT3. Further the transfection of cells with DN PKCdelta
      reduced, while PKCdelta activation enhanced, STAT3 phosphorylation in the
      presence of shear. Transfection of cells with a dominant negative mutant of STAT3
      enhanced eNOS promoter activity and nitric oxide production in response to shear.
      Finally, we found that mutating the STAT3 binding site sequence within the eNOS
      promoter increased promoter activity in response to shear and that this was no
      longer inhibited by bryostatin. In conclusion, shear decreases PKCdelta activity
      and, subsequently, reduces STAT3 binding to the eNOS promoter. This signaling
      pathway plays a previously unidentified role in the regulation of eNOS expression
      by shear stress.

PMID- 19118092
TI  - Early response of gene clusters is associated with mouse lung resistance or
      sensitivity to cigarette smoke.
AB  - We have investigated the effects of cigarette smoke exposure in three different
      strains of mice. DBA/2 and C57BL/6J are susceptible to smoke and develop
      different lung changes in response to chronic exposure, whereas ICR mice are
      resistant to smoke and do not develop emphysema. The present study was carried
      out to determine early changes in the gene expression profile of mice exposed to
      cigarette smoke with either a susceptible or resistant phenotype. The three
      strains of mice were exposed to smoke from three cigarettes per day, 5 days/wk,
      for 4 wk. Microarray analysis was carried out on total RNA extracted from the
      lung using the Affymetrix platform. Cigarette smoke modulates several clusters of
      genes (i.e., proemphysematous, acute phase response, and cell adhesion) in smoke
      sensitive DBA/2 or C57BL/6J strains, but the same genes are not altered by smoke
      in ICR resistant mice. Only a few genes were commonly modulated by smoke in the
      three strains of mice. This pattern of gene expression suggests that the response
      to smoke is strain-dependent and may involve different molecular signaling
      pathways. Real-time quantitative PCR was used to verify the pattern of modulation
      of selected genes and their potential biological relevance. We conclude that gene
      expression response to smoke is highly dependent on the mouse genetic background.
      We speculate that the definition of gene clusters associated, to various degrees,
      with mouse susceptibility or resistance to smoke may be instrumental in defining
      the molecular basis of the individual response to smoke-induced lung injury in
      humans.

PMID- 19118093
TI  - Trauma-hemorrhagic shock-induced pulmonary epithelial and endothelial cell injury
      utilizes different programmed cell death signaling pathways.
AB  - Intestinal ischemia after trauma-hemorrhagic shock (T/HS) results in gut barrier
      dysfunction and the production/release of biologically active and tissue
      injurious factors in the mesenteric lymph, which, in turn, causes acute lung
      injury and a systemic inflammatory state. Since T/HS-induced lung injury is
      associated with pulmonary endothelial and epithelial cell programmed cell death
      (PCD) and was abrogated by mesenteric lymph duct ligation, we sought to
      investigate the cellular pathways involved. Compared with trauma-sham shock
      (T/SS) rats, a significant increase in caspase-3 and M30 expression was detected
      in the pulmonary epithelial cells undergoing PCD, whereas apoptosis-inducing
      factor (AIF), but not caspase-3, was detected in endothelial cells undergoing
      PCD. This AIF-mediated pulmonary endothelial PCD response was validated in an in
      situ femoral vein assay where endothelial cells were found to express AIF but not
      caspase-3. To complement these studies, human umbilical vein endothelial cell
      (HUVEC), human lung microvascular endothelial cell (HLMEC), and human alveolar
      type II epithelial cell (A549) lines were used as in vitro models. T/HS lymph
      induced the nuclear translocation of AIF in HUVEC and HLMEC, and caspase
      inhibition in these cells did not afford any cytoprotection. For proof of
      principle, AIF silencing in HUVEC reversed the cytotoxic effects of T/HS on cell
      viability and DNA fragmentation. In A549 cells, T/HS lymph activated caspase-3
      mediated apoptosis, which was partially abrogated by N-benzyloxycarbonyl-Val-Ala
      Asp (zVAD). Additionally, T/HS lymph did not cause the nuclear translocation of
      AIF in A549 cells. Collectively, T/HS-induced pulmonary endothelial PCD occurs
      via an AIF-dependent caspase-independent pathway, whereas epithelial cells
      undergo apoptosis by a caspase-dependent pathway.

PMID- 19118094
TI  - Ventromedial nucleus neurons are less sensitive to leptin excitation in rats bred
      to develop diet-induced obesity.
AB  - Maternal obesity accentuates offspring obesity in dams bred to develop diet
      induced obesity (DIO) on a 31% fat, high energy (HE) diet but has no effect on
      offspring of diet-resistant (DR) dams. Only DIO dams became obese on HE diet when
      they and DR dams were fed 5% fat chow or HE diets throughout gestation and
      lactation. Leptin sensitivity of dissociated arcuate (ARC) and ventromedial (VMN)
      hypothalamic nucleus neurons from the 3- to 4-wk-old offspring was assessed using
      fura-2 calcium imaging to monitor leptin-induced changes in intracellular calcium
      ([Ca(2+)](i)) as an index of neuronal activity. At 0.1, 1, 10 fmol/l leptin,
      approximately 4 times more VMN and ARC neurons were excited than inhibited by
      leptin. In the VMN, leptin excited up to 41% fewer neurons, and these excited
      neurons were less sensitive to increasing doses of leptin in DIO compared with DR
      offspring. Also, maternal HE diet intake decreased the percentage of leptin
      excited VMN neurons in both DIO and DR offspring and decreased the percentage of
      leptin-inhibited VMN neurons by 36% only in DIO offspring. In the ARC, there were
      no genotype or maternal diet effects on the percentage of ARC neurons excited by
      leptin. However, those DR neurons that were leptin excited were more sensitive to
      leptin than were those from DIO offspring. These data suggest that reduced
      responsiveness of DIO VMN neurons to leptin's excitatory effects may be an
      important contributing factor to the reduced anorectic and thermogenic leptin
      responsiveness of DIO rats in vivo.

PMID- 19118095
TI  - ATP-induced vasodilation and purinergic receptors in the human leg: roles of
      nitric oxide, prostaglandins, and adenosine.
AB  - Plasma ATP is thought to contribute to the local regulation of skeletal muscle
      blood flow. Intravascular ATP infusion can induce profound limb muscle
      vasodilatation, but the purinergic receptors and downstream signals involved in
      this response remain unclear. This study investigated: 1) the role of nitric
      oxide (NO), prostaglandins, and adenosine as mediators of ATP-induced limb
      vasodilation and 2) the expression and distribution of purinergic P(2) receptors
      in human skeletal muscle. Systemic and leg hemodynamics were measured before and
      during 5-7 min of femoral intra-arterial infusion of ATP [0.45-2.45 micromol/min]
      in 19 healthy male subjects with and without coinfusion of N(G)-monomethyl-l
      arginine (l-NMMA; NO formation inhibitor; 12.3 +/- 0.3 (SE) mg/min), indomethacin
      (INDO; prostaglandin formation blocker; 613 +/- 12 microg/min), and/or
      theophylline (adenosine receptor blocker; 400 +/- 26 mg). During control
      conditions, ATP infusion increased leg blood flow (LBF) from baseline conditions
      by 1.82 +/- 0.14 l/min. When ATP was coinfused with either l-NMMA, INDO, or l
      NMMA + INDO combined, the increase in LBF was reduced by 14 +/- 6, 15 +/- 9, and
      39 +/- 8%, respectively (all P < 0.05), and was associated with a parallel
      lowering in leg vascular conductance and cardiac output and a compensatory
      increase in leg O(2) extraction. Infusion of theophylline did not alter the ATP
      induced leg hyperemia or systemic variables. Real-time PCR analysis of the mRNA
      content from the vastus lateralis muscle of eight subjects showed the highest
      expression of P(2Y2) receptors of the 10 investigated P(2) receptor subtypes.
      Immunohistochemistry showed that P(2Y2) receptors were located in the endothelium
      of microvessels and smooth muscle cells, whereas P(2X1) receptors were located in
      the endothelium and the sacrolemma. Collectively, these results indicate that NO
      and prostaglandins, but not adenosine, play a role in ATP-induced vasodilation in
      human skeletal muscle. The expression and localization of the nucleotide
      selective P(2Y2) and P(2X1) receptors suggest that these receptors may mediate
      ATP-induced vasodilation in skeletal muscle.

PMID- 19118096
TI  - Attenuated PGI2 synthesis in obese Zucker rats.
AB  - In obesity, skeletal muscle blood flow during exercise (functional hyperemia) is
      impaired. We have indirectly demonstrated that an altered arachidonic acid
      metabolism is responsible for the impaired functional vasodilation in the obese
      Zucker rat (OZR), a model of obesity. In this study, we tested the hypothesis
      that there is an impaired release of PGI(2) due to a nitration of PGI(2) synthase
      (PGIS), which is associated with a decreased prostanoid receptor expression.
      PGI(2), PGE(2), and thromboxane A(2) (TXA(2)) release were determined in vitro
      using ELISA under basal conditions and in response to arachidonic acid (AA)
      administration (50 microM). Immunofluorescence of PGI(2) and TXA(2) receptors (IP
      and TP, respectively) was determined in dispersed vascular smooth muscle cells
      (VSMCs). Nitration of tyrosine residues of the PGIS enzyme was determined using
      immunoprecipitation and Western blot analysis. Following AA administration,
      PGI(2) and PGE(2) release were attenuated in OZR compared with lean Zucker rats
      (LZR; controls). Basal and AA-induced TXA(2) release were not significantly
      different between groups. IP and TP immunofluorescence were not significantly
      different between OZR and LZR groups. OZR exhibited elevated nitration of
      tyrosine residues of PGIS compared with LZR. These results suggest that
      alterations in the PGI(2) pathway (attenuated PGI(2) synthesis), and not the
      TXA(2) pathway (normal TXA(2) synthesis/no change in TP receptor expression),
      underlie the attenuated functional hyperemia in the OZR.

PMID- 19118097
TI  - Protein synthesis and the expression of growth-related genes are altered by
      running in human vastus lateralis and soleus muscles.
AB  - Recent evidence suggests aerobic exercise may help preserve soleus muscle mass
      during unloading. The purpose of this investigation was to examine the muscle
      specific metabolic response to running as it relates to muscle growth. Mixed
      muscle protein synthesis [fractional synthetic rate (FSR)] and gene expression
      (GE) were examined in the vastus lateralis (VL) and soleus (SOL) muscles from
      eight men (26 +/- 2 yr; Vo(2max) 63 +/- 2 ml.kg(-1).min(-1)) before and after a
      45-min level-grade treadmill run at 77 +/- 1% intensity. Muscle glycogen
      utilization was similar between muscles. Resting FSR was similar between the VL
      (0.080 +/- 0.007 %/h) and SOL (0.086 +/- 0.008 %/h) and was higher (P < 0.05) 24
      h postexercise compared with rest for both muscles. The absolute change in FSR
      was not different between muscles (0.030 +/- 0.007 vs. 0.037 +/- 0.012 %/h for VL
      and SOL). At baseline, myostatin GE was approximately twofold higher (P < 0.05)
      in SOL compared with VL, while no other muscle-specific differences in GE were
      present. After running, myostatin GE was suppressed (P < 0.05) in both muscles at
      4 h and was higher (P < 0.05) than baseline at 24 h for VL only. Muscle
      regulatory factor 4 mRNA was elevated (P < 0.05) at 4 h in both SOL and VL; MyoD
      and peroxisome-proliferator-activated receptor-gamma coactivator-1alpha (PGC
      1alpha) were higher (P < 0.05) at 4 h, and forkhead box [FOXO]3A was higher at 24
      h in SOL only, while muscle-RING-finger protein-1 (MuRF-1) was higher (P < 0.05)
      at 4 h in VL only. Myogenin and atrogin-1 GE were unaltered. The similar
      increases between muscles in FSR support running as part of the exercise
      countermeasure to preserve soleus mass during unloading. The subtle differences
      in GE suggest a potential mechanism for muscle-specific adaptations to chronic
      run training.

PMID- 19118098
TI  - Role of central nervous system aldosterone synthase and mineralocorticoid
      receptors in salt-induced hypertension in Dahl salt-sensitive rats.
AB  - In Dahl salt-sensitive (S) rats, high salt intake increases cerebrospinal fluid
      (CSF) Na(+) concentration ([Na(+)]) and blood pressure (BP).
      Intracerebroventricular (ICV) infusion of a mineralocorticoid receptor (MR)
      blocker prevents the hypertension. To assess the role of aldosterone locally
      produced in the brain, we evaluated the effects of chronic central blockade with
      the aldosterone synthase inhibitor FAD286 and the MR blocker spironolactone on
      changes in aldosterone and corticosterone content in the hypothalamus and the
      increase in CSF [Na(+)] and hypertension induced by high salt intake in Dahl S
      rats. After 4 wk of high salt intake, plasma aldosterone and corticosterone were
      not changed, but hypothalamic aldosterone increased by approximately 35% and
      corticosterone tended to increase in Dahl S rats, whereas both steroids decreased
      by approximately 65% in Dahl salt-resistant rats. In Dahl S rats fed the high
      salt diet, ICV infusion of FAD286 or spironolactone did not affect the increase
      in CSF [Na(+)]. ICV infusion of FAD286 prevented the increase in hypothalamic
      aldosterone and 30 mmHg of the 50-mmHg BP increase induced by high salt intake.
      ICV infusion of spironolactone fully prevented the salt-induced hypertension.
      These results suggest that, in Dahl S rats, high salt intake increases
      aldosterone synthesis in the hypothalamus and aldosterone acts as the main MR
      agonist activating central pathways contributing to salt-induced hypertension.

PMID- 19118099
TI  - Expression of rainbow trout glucose transporters GLUT1 and GLUT4 during in vitro
      muscle cell differentiation and regulation by insulin and IGF-I.
AB  - Insulin is an important factor for the maintenance of glucose homeostasis,
      enhancing glucose uptake in its target tissues in a process that has been
      conserved between fish and mammals. In fish skeletal muscle cells, like in
      mammals, insulin promotes GLUT4 translocation to the plasma membrane and,
      consequently, glucose uptake, but its role regulating the expression of glucose
      transporters in vitro has not been demonstrated to date. Thus, we investigated
      the expression of GLUT4 and GLUT1 throughout skeletal muscle cell differentiation
      and their regulation by insulin and IGF-I using a primary culture of trout muscle
      cells. GLUT4 expression gradually increased during the muscle cell
      differentiation process, whereas GLUT1 expression remained fairly constant.
      Insulin and IGF-I similarly increased the mRNA levels of GLUT4 in myoblasts and
      myotubes. On the other hand, IGF-I appeared to be more potent than insulin in
      stimulating GLUT1 expression, particularly at the myoblast stage. Therefore, this
      work provides the first demonstration in nonmammalian vertebrates that insulin
      and IGF-I may act directly on trout muscle cells to regulate the expression of
      GLUT4 and GLUT1.

PMID- 19118100
TI  - Ghrelin modulates electrical activity of area postrema neurons.
AB  - Ghrelin, a peptide hormone secreted from the stomach, is known to have a potent
      appetite-stimulating activity. Recently, it has been shown that area postrema
      (AP), a caudal brain stem center that lacks a blood-brain barrier, is a key site
      of activity for ghrelin in stimulating appetite and regulating pancreatic protein
      secretion. In this study, we have examined the ability of ghrelin to regulate the
      electrical activity of area postrema neurons using patch-clamp electrophysiology.
      Using current-clamp configuration, we found that at a concentration of 10 nM,
      ghrelin caused inhibition in 19% of neurons tested, while a further 19% were
      excited by similar application of ghrelin. The remaining 62% of AP neurons were
      insensitive to ghrelin. These effects were concentration dependent, with an
      apparent EC(50) of 1.9 nM. Voltage-clamp recordings revealed that ghrelin caused
      a potentiation of voltage-gated K(+) currents in neurons that exhibited a
      hyperpolarization and a potentiation of a depolarizing nonspecific cation current
      (NSCC) in those neurons that exhibited a depolarization of membrane potential.
      These are the first data showing that ghrelin exerts a direct effect on
      electrical activity of AP neurons and supports the notion that ghrelin can act
      via the AP to regulate energy homeostasis.

PMID- 19118101
TI  - Adenosine A1 and A2a receptors modulate insulinemia, glycemia, and lactatemia in
      fetal sheep.
AB  - Adenosine A(1) and A(2A) receptor subtypes modulate metabolism in adult mammals.
      This study was designed to determine the role of these receptors in regulating
      plasma levels of insulin, glucose, and lactate in 20 chronically catheterized
      fetal sheep (>0.8 term). In normoxic fetuses (Pa(O(2)) approximately 24 Torr),
      systemic blockade of A(1) receptors with DPCPX (n = 6) increased plasma
      concentrations of insulin, glucose, and lactate, but antagonism of A(2A)
      receptors with ZM-241385 (n = 5) had no significant effects. Intravascular
      administration of adenosine (n = 9) reduced insulin concentrations and elevated
      glucose and lactate levels. DPCPX (n = 6) augmented the glycemic and lactatemic
      responses of adenosine. In contrast, ZM241385 (n = 5) virtually abolished
      adenosine-induced hyperglycemia and hyperlactatemia. Isocapnic hypoxia (Pa(O(2))
      approximately 13 Torr) suppressed insulinemia and enhanced glycemia and
      lactatemia, but only the hyperglycemia was blunted by blockade of A(1) (n = 6) or
      A(2A) (n = 6) receptors. We conclude that 1) endogenous adenosine via A(1)
      receptors depresses plasma concentrations of insulin, glucose, and lactate; 2)
      exogenous adenosine via A(2A) receptors increases glucose and lactate levels, but
      these responses are dampened by stimulation of A(1) receptors; and 3) hypoxia,
      which increases endogenous adenosine concentrations, induces hyperglycemia that
      is partly mediated by activation of A(1) and A(2A) receptors. We predict that
      adenosine, via A(1) receptors, facilitates at least 12% of glucose uptake and
      utilization in normoxic fetuses.

PMID- 19118102
TI  - B cells from periodontal disease patients express surface Toll-like receptor 4.
AB  - Chronic systemic inflammation links periodontal disease (PD) to increased
      incidence of cardiovascular disease. Activation of TLRs, particularly TLR4,
      promotes chronic inflammation in PD by stimulating myeloid cells. B cells from
      healthy individuals are generally refractory to TLR4 agonists as a result of low
      surface TLR4 expression. Unexpectedly, a significantly increased percentage of
      gingival and peripheral blood B cells from patients with PD expressed surface
      TLR4. Surface expression correlated with an active TLR4 promoter that mimicked
      the TLR4 promoter in neutrophils. B cells from PD patients were surface myeloid
      differentiation protein 2-positive and also packaged the enhancer of a
      proinflammatory cytokine, IL-1 beta, into an active structure, demonstrating that
      these cells harbor key characteristics of proinflammatory cell types.
      Furthermore, B cells lacked activating signatures of a natural IL-1 beta
      inhibitor, IL-1 receptor antagonist. Surprisingly, despite multiple signatures of
      proinflammatory cells, freshly isolated B cells from PD patients had decreased
      expression of TLR pathway genes compared with B cells from healthy individuals.
      Decreases in inflammatory gene expression were even more dramatic in B cells
      stimulated with a TLR4 ligand from a periodontal pathogen, Porphyromonas
      gingivalis LPS 1690. In contrast, B cell TLR4 was not activated by the prototypic
      TLR4 ligand Escherichia coli LPS. These findings raise the unexpected possibility
      that TLR4 engagement modulates B cell activation in PD patients.

PMID- 19118103
TI  - Identification of biologically active peptides that inhibit binding of human
      CXCL8 to its receptors from a random phage-epitope library.
AB  - A random bacteriophage peptide library was used to map structural features of
      human (h)CXCR1 and hCXCR2 by determining the epitopes of neutralizing mAb 5A12
      anti-hCXCR1 and mAb 6C6 anti-hCXCR2. After three rounds of biopanning, five mAb5
      A12- and four mAb 6C6-binding peptides were identified from a 6-mer peptide
      library. Consensus sequences (S/T)(1)(F/A/N/D)(2)(I/M)(3)W(4)D(5)F(6) and
      F/L/M)(1)W(2)(D/N/L)(3)D(4)F(5)W(6) were deduced from sequences of these
      peptides. They correspond to a highly conserved N-domain sequence (9)MWDF(12) of
      hCXCR1 and (13)DFW(15) of hCXCR2. The phage bearing the peptides showed specific
      binding to immobilized mAb 5A12 or mAb 6CC, and over 86% of phages bound were
      competitively inhibited by free synthetic peptides. In FACScan analysis, all
      selected phage peptides were able to strongly inhibit the binding of mAb 5A12 and
      mAb 6C6 to hCXCR1- and hCXCR2-transfected preB 300-19 murine cells. Furthermore,
      synthetic peptides of the corresponding phage epitopes were effective in blocking
      the antibody-CXCR1/2 interactions and to inhibit the binding of hCXCL8 to hCXCR1
      and hCXCR2 transfectants. Peptides 5A12/2 (SAMWDF) and 6C6/1 (FWDDFW) competed
      effectively for (125)I-hCXCL8 binding to hCXCR1 and hCXCR2 with IC(50),
      respectively, equal to 10 muM and 5.4 muM. Calcium release and chemotaxis of
      hCXCR1/2 transfectants or human neutrophils were inhibited by all peptides in a
      dose-dependent manner. Furthermore, the peptide 6C6/1 FWDDFW showed inhibitory
      effects on chemotaxis of human netrophils induced by hCXCR2 chemokines such as
      hCXCL1-3 and hCXCL5. Specificities of peptides 5A12/2 and 6C6/1 were assessed
      with hCXCR3, hCXCR4, hCXCR5, hCCR3, and hCCR5 receptors. In vivo, peptides 5A12/2
      and p6C6/1 blockade hCXCL8-induced neutrophil recruitment in skin inflammation in
      rabbits. Taken together, these data demonstrate that phage-display analysis
      provides information about the relative location of amino acids on the N-domain
      surfaces of hCXCR1 and hCXCR2 proteins using antibody imprints of the receptor
      surface structure. The derived mimotopes could be used as inhibitors of hCXCL8
      induced activities related to its interaction with the N-domain of hCXCR1 and
      hCXCR2.

PMID- 19118104
TI  - OAG induces an additional PKC-, PI3K-, and Rac2-mediated signaling pathway up
      regulating NOX2 activity, independently of Ca2+ entry.
AB  - The requirement of calcium ion (Ca(2)(+)) entry for neutrophil NADPH oxidase
      (NOX2) regulation is clearly established. However, its role in the signaling
      pathway leading to NOX2 activation is still elusive. 1-oleoyl-2-acetyl-sn
      glycerol (OAG) causes an increase in NOX2 activity and has been shown to directly
      modulate Ca(2)(+) channels unrelated to the well-known store-operated Ca(2)(+)
      entry (SOCE) mechanism. In our study, we have investigated the potential role of
      OAG in Ca(2)(+) influx-mediated NOX2 activity in neutrophil-like-differentiated
      HL-60 cells to further characterize second signals involved in the regulation of
      NOX2. OAG inhibited fMLF- and thapsigargin-induced Ca(2)(+) entry, a phenomenon
      that was not restored by protein kinase C (PKC) or PI3K blockade. Addition of OAG
      resulted in a rapid decrease of maximal intracellular Ca(2)(+) concentration
      induced by thapsigargin. Both results suggest that OAG has an inhibitory effect,
      independent of PI3K and PKC, on the regulation of SOCE. In contrast to SOCE
      inhibition, OAG-induced NOX2 activation was mediated by PKC and PI3K. Our data
      establish that both kinases exert their effects through the regulation of Rac2
      activity. In addition, OAG potentiated the effect of fMLF on the activation of
      NOX2 and led to a discernible activity of NOX2 upon thapsigargin stimulation. In
      conclusion, our results demonstrate that an additional PKC- and/or PI3K-dependent
      signal may act in synergy with Ca(2)(+) influx to trigger NOX2 activation.

PMID- 19118105
TI  - Quantitative assessment of the distributions of membrane conductances involved in
      action potential backpropagation along basal dendrites.
AB  - Basal dendrites of prefrontal cortical neurons receive strong synaptic drive from
      recurrent excitatory synaptic inputs. Synaptic integration within basal dendrites
      is therefore likely to play an important role in cortical information processing.
      Both synaptic integration and synaptic plasticity depend crucially on dendritic
      membrane excitability and the backpropagation of action potentials. We carried
      out multisite voltage-sensitive dye imaging of membrane potential transients from
      thin basal branches of prefrontal cortical pyramidal neurons before and after
      application of channel blockers. We found that backpropagating action potentials
      (bAPs) are predominantly controlled by voltage-gated sodium and A-type potassium
      channels. In contrast, pharmacologically blocking the delayed rectifier
      potassium, voltage-gated calcium, or I(h) conductance had little effect on
      dendritic AP propagation. Optically recorded bAP waveforms were quantified and
      multicompartmental modeling was used to link the observed behavior with the
      underlying biophysical properties. The best-fit model included a nonuniform
      sodium channel distribution with decreasing conductance with distance from the
      soma, together with a nonuniform (increasing) A-type potassium conductance. AP
      amplitudes decline with distance in this model, but to a lesser extent than
      previously thought. We used this model to explore the mechanisms underlying two
      sets of published data involving high-frequency trains of APs and the local
      generation of sodium spikelets. We also explored the conditions under which I(A)
      down-regulation would produce branch strength potentiation in the proposed model.
      Finally, we discuss the hypothesis that a fraction of basal branches may have
      different membrane properties compared with sister branches in the same dendritic
      tree.

PMID- 19118106
TI  - Modularity of endpoint force patterns evoked using intraspinal microstimulation
      in treadmill trained and/or neurotrophin-treated chronic spinal cats.
AB  - Chronic spinal cats with neurotrophin-secreting fibroblasts (NTF) transplants
      recover locomotor function. To ascertain possible mechanisms, intraspinal
      microstimulation was used to examine the lumbar spinal cord motor output of four
      groups of chronic spinal cats: untrained cats with unmodified-fibroblasts graft
      (Op-control) or NTF graft and locomotor-trained cats with unmodified-fibroblasts
      graft (Trained) or NTF graft (Combination). Forces generated via intraspinal
      microstimulation at different hindlimb positions were recorded and interpolated,
      generating representations of force patterns at the paw. Electromyographs (EMGs)
      of hindlimb muscles, medial gastrocnemius, tibialis anterior, vastus lateralis,
      and biceps femoris posterior, were also collected to examine relationships
      between activated muscles and force pattern types. The same four force pattern
      types obtained in spinal-intact cats were found in chronic spinal cats.
      Proportions of force patterns in spinal cats differed significantly from those in
      intact cats, but no significant differences in proportions were observed among
      individual spinal groups (Op-control, NTF, Trained, and Combination). However,
      the proportions of force patterns differed significantly between trained (Trained
      and Combination) and untrained groups (Op-control and NTF). Thus the frequency of
      expression of some response types was modified by injury and to a lesser extent
      by training. Force pattern laminar distribution differed in spinal cats compared
      with intact, with more responses obtained dorsally (0-1,000 microm) and fewer
      ventrally (3,200-5,200 microm). EMG analysis demonstrated that muscle activity
      highly predicted some force pattern types and was independent of hindlimb
      position. We conclude that spinal motor output modularity is preserved after
      injury.

PMID- 19118107
TI  - Contribution of commissural projections to bulbospinal activation of locomotion
      in the in vitro neonatal rat spinal cord.
AB  - Commissural projections are required for left-right coordination during
      locomotion. However, their role, if any, in rhythm production is unknown. This
      study uses the neonatal rat in vitro brain stem-spinal cord model to examine the
      rostrocaudal distribution of locomotor-related commissural projections and study
      whether commissural connections are needed for the generation of hindlimb
      rhythmic activity in response to electrical stimulation of the brain stem.
      Midsagittal lesions were made at a wide range of rostrocaudal levels. Locomotor
      like activity persisted in some preparations despite midsagittal lesions
      extending from C(1) to the mid-L(1) level or from the conus medullaris to the
      T(12/13) junction. In some preparations, midsagittal lesions throughout the
      entire spinal cord had no effect on locomotor-like activity if two or three
      contiguous segments remained intact. Those bridging segments had to include the
      T(13) and/or L(1) levels. These observations suggested that commissural
      projections in the thoracolumbar junction region were critical. However,
      locomotor-like activity was also elicited in preparations with limited
      midsagittal lesions focused on the thoracolumbar junction (T(12) through L(1) or
      L(2) inclusive). In other experiments, locomotor-like activity was evoked by bath
      applied 5-hydroxytryptamine (5-HT) and N-methyl-d-aspartate (NMDA). Appropriate
      side-to-side coordination was observed, even when only one segment remained
      bilaterally intact. Commissural projections traversing the thoracolumbar junction
      region were most effective. In combination, these results suggest that locomotor
      related commissural projections are redundantly distributed along a bi
      directional gradient that centers on the thoracolumbar junction. This commissural
      system not only provides a robust left-right coordinating mechanism but also
      supports locomotor rhythm generation in response to brain stem stimulation.

PMID- 19118108
TI  - The pontomedullary reticular formation contributes to the compensatory postural
      responses observed following removal of the support surface in the standing cat.
AB  - This study was designed to determine the contribution of reticular neurons in the
      pontomedullary reticular formation (PMRF) to the postural responses produced to
      compensate for an unexpected perturbation. We recorded the activity of 48 neurons
      in the PMRF, including 41 reticulospinal neurons, to removal of the support
      surface under each of the four limbs in four cats. The perturbations produced
      robust postural responses that were divided into three periods: an initial
      postural response (P1) that displaced the center of vertical pressure over the
      two diagonal supporting limbs; a secondary response (P2) during which the cat
      restored a tripedal support pattern; and a prolonged tertiary response (P3) that
      maintained a stable posture over all three supporting limbs. Most (44/48)
      reticular neurons showed modified activity to perturbation of at least one limb
      and a majority (39/48) showed changes in activity to perturbations of more than
      one limb. A few (7/48) discharged to perturbations of all four limbs. Discharge
      frequency in neurons showing increased activity during P1 was relatively high
      (>100 Hz in 57% of the neurons responding to perturbations of either the left or
      right forelimbs, lFl and rFL) and of short latency (17 ms for the lFL and 14 ms
      for the rFL). Discharge activity in most neurons was sustained throughout P2 and
      P3 but at a reduced level. These data show that neurons in the PMRF discharge
      strongly in response to unexpected perturbations and in a manner consistent with
      a contribution to the compensatory responses that restore equilibrium.

PMID- 19118109
TI  - Reflex control of the human inner ear: a half-octave offset in medial efferent
      feedback that is consistent with an efferent role in the control of masking.
AB  - The high sensitivity and frequency selectivity of the mammalian cochlea is due to
      amplification produced by outer hair cells (OHCs) and controlled by medial
      olivocochlear (MOC) efferents. Data from animals led to the view that MOC fibers
      provide frequency-specific inhibitory feedback; however, these studies did not
      measure intact MOC reflexes. To test whether MOC inhibition is primarily at the
      frequency that elicits the MOC activity, acoustically elicited MOC effects were
      quantified in humans by the change in otoacoustic emissions produced by 60-dB SPL
      tone and half-octave-band noise elicitors at different frequencies relative to a
      40-dB SPL, 1-kHz probe tone. On average, all elicitors produced MOC effects that
      were skewed (elicitor frequencies -1 octave below the probe produced larger
      effects than those -1 octave above). The largest MOC effects were from elicitors
      below the probe frequency for contra- and bilateral elicitors but were from
      elicitors centered at the probe frequency for ipsilateral elicitors. Typically,
      ipsilateral elicitors produced larger effects than contralateral elicitors and
      bilateral elicitors produced effects near the ipsi+contra sum. Elicitors at
      levels down to 30-dB SPL produced similar patterns. Tuning curves (TCs)
      interpolated from these data were V-shaped with Q10s approximately 2. These are
      sharper than MOC-fiber TCs found near 1 kHz in cats and guinea pigs. Because
      cochlear amplification is skewed (more below the best frequency of a cochlear
      region), these data are consistent with an anti-masking role of MOC efferents
      that reduces masking by reducing the cochlear amplification seen at 1 kHz.

PMID- 19118110
TI  - The Na+/Ca2+ exchanger inhibitor, KB-R7943, blocks a nonselective cation channel
      implicated in chemosensory transduction.
AB  - The mechanism(s) of olfactory transduction in invertebrates remains to be fully
      understood. In lobster olfactory receptor neurons (ORNs), a nonselective sodium
      gated cation (SGC) channel, a presumptive transient receptor potential (TRP)C
      channel homolog, plays a crucial role in olfactory transduction, at least in part
      by amplifying the primary transduction current. To better determine the
      functional role of the channel, it is important to selectively block the channel
      independently of other elements of the transduction cascade, causing us to search
      for specific pharmacological blockers of the SGC channel. Given evidence that the
      Na(+)/Ca(2+) exchange inhibitor, KB-R7943, blocks mammalian TRPC channels, we
      studied this probe as a potential blocker of the lobster SGC channel. KB-R7943
      reversibly blocked the SGC current in both inside- and outside-out patch
      recordings in a dose- and voltage-dependent manner. KB-R7943 decreased the
      channel open probability without changing single channel amplitude. KB-R7943 also
      reversibly and in a dose-dependent manner inhibited both the odorant-evoked
      discharge of lobster ORNs and the odorant-evoked whole cell current. Our findings
      strongly imply that KB-R7943 potently blocks the lobster SGC channel and likely
      does so directly and not through its ability to block the Na(+)/Ca(2+) exchanger.

PMID- 19118111
TI  - Theta and gamma coherence along the septotemporal axis of the hippocampus.
AB  - Theta and gamma rhythms synchronize neurons within and across brain structures.
      Both rhythms are widespread within the hippocampus during exploratory behavior
      and rapid-eye-movement (REM) sleep. How synchronous are these rhythms throughout
      the hippocampus? The present study examined theta and gamma coherence along the
      septotemporal (long) axis of the hippocampus in rats during REM sleep, a
      behavioral state during which theta signals are unaffected by external sensory
      input or ongoing behavior. Unilateral entorhinal cortical inputs are thought to
      play a prominent role in the current generation of theta, whereas current
      generation of gamma is primarily due to local GABAergic neurons. The septal 50%
      (4-5 mm) of the dentate gyrus (DG) receives a highly divergent, unilateral
      projection from any focal point along a lateral band of entorhinal neurons near
      the rhinal sulcus. We hypothesized that theta coherence in the target zone
      (septal DG) of this divergent entorhinal input would not vary, while gamma
      coherence would significantly decline with distance in this zone. However, both
      theta and gamma coherence decreased significantly along the long axis in the
      septal 50% of the hippocampus across both DG and CA1 electrode sites. In
      contrast, theta coherence between homotypic (e.g., DG to DG) sites in the
      contralateral hemisphere ( approximately 3-5 mm distant) were quite high (
      approximately 0.7-0.9), much greater than theta coherence between homotypic sites
      3-5 mm distant ( approximately 0.4-0.6) along the long axis. These findings
      define anatomic variation in both rhythms along the longitudinal axis of the
      hippocampus, indicate the bilateral CA3/mossy cell projections are the major
      determinant of theta coherence during REM, and demonstrate that theta coherence
      varies as a function of anatomical connectivity rather than physical distance. We
      suggest CA3 and entorhinal inputs interact dynamically to generate theta field
      potentials and advance the utility of theta and gamma coherence as indicators of
      hippocampal dynamics.

PMID- 19118112
TI  - Fusion of visual and vestibular tilt cues in the perception of visual vertical.
AB  - We investigated the effect of visual and vestibular body-tilt cues on the
      subjective visual vertical (SVV) in six human observers at roll tilts of 0, 60,
      and 120 degrees . Subjects adjusted a small luminous test line parallel to the
      perceived direction of gravity, in the presence of a large peripheral visual
      frame line. These settings, referred to as the frame SVV, were compared with the
      SVV in complete darkness (dark SVV). The frame SVV was virtually identical to the
      dark SVV for frame lines parallel or orthogonal to the dark SVV. Away from these
      neutral positions, the frame induced a periodic SVV modulation, which was small
      in upright observers, but became quite pronounced when subjects were tilted. For
      upright, where the dark SVV was very accurate, the frame SVV showed errors in
      both directions, following a roughly symmetrical pattern. At 120 degrees tilt,
      where the dark SVV invariably showed tilt undercompensation (A-effect), the frame
      effect became asymmetrical, with a stronger tendency to improve than to worsen
      accuracy. We tested whether our findings could be explained by two spatial
      orientation models: Mittelstaedt's idiotropic model and a Bayesian scheme with a
      stage for the processing of visual cues. Both models show a periodic frame effect
      that becomes stronger with increasing body tilt and can explain why frame lines
      parallel or perpendicular to the dark SVV are ineffective. Based on their
      performance, we conclude that perception of the visual vertical is based on a
      centrally weighted fusion of visual, vestibular, and egocentric references.

PMID- 19118113
TI  - Early but not late administration of glucagon-like peptide-2 following ileo-cecal
      resection augments putative intestinal stem cell expansion.
AB  - Expansion of intestinal progenitors and putative stem cells (pISC) occurs early
      and transiently following ileo-cecal resection (ICR). The mechanism controlling
      this process is not defined. We hypothesized that glucagon-like peptide-2 (GLP-2)
      would augment jejunal pISC expansion only when administered to mice immediately
      after ICR. Since recent reports demonstrated increases in intestinal insulin-like
      growth factor (IGF)-I following GLP-2 administration, we further hypothesized
      that increased intestinal IGF-I expression would correlate with pISC expansion
      following ICR. To assess this, GLP-2 or vehicle was administered to mice either
      immediately after resection (early) or before tissue harvest 6 wk following ICR
      (late). Histological analysis quantified proliferation and intestinal
      morphometrics. Serum levels of GLP-2 were measured by ELISA and jejunal IGF-I
      mRNA by qRT-PCR. Expansion of jejunal pISC was assessed by fluorescent-activated
      cell sorting of side population cells, immunohistochemistry for phosphorylated
      beta-catenin at serine 552 (a pISC marker), percent of crypt fission, and total
      numbers of crypts per jejunal circumference. We found that early but not late GLP
      2 treatment after ICR significantly augmented pISC expansion. Increases in
      jejunal IGF-I mRNA correlated temporally with early pISC expansion and effects of
      GLP-2. Early GLP-2 increased crypt fission and accelerated adaptive increases in
      crypt number and intestinal caliber. GLP-2 increased proliferation and intestinal
      morphometrics in all groups. This study shows that, in mice, GLP-2 promotes
      jejunal pISC expansion only in the period immediately following ICR. This is
      associated with increased IGF-I and accelerated adaptive increases in mucosal
      mass. These data provide clinical rationale relevant to the optimal timing of GLP
      2 in patients with intestinal failure.

PMID- 19118114
TI  - Lymphocyte-derived interferon-gamma mediates ischemia-reperfusion-induced
      leukocyte and platelet adhesion in intestinal microcirculation.
AB  - Although previous studies have implicated lymphocytes in the gut microvascular
      and inflammatory responses to ischemia-reperfusion (I/R), the lymphocyte
      population and lymphocyte-derived products that mediate these responses have not
      been defined. Platelet and leukocyte adhesion was measured in intestinal
      postcapillary venules of wild-type (WT) mice and mice genetically deficient in
      either CD4+ T cells (CD4-/-), CD8+ T cells (CD8-/-), B cells (B cell-/-), or
      interferon-gamma (IFN-gamma-/-) subjected to 45 min of ischemia and 4 h of
      reperfusion. The I/R-induced platelet and leukocyte recruitment responses were
      also evaluated following adoptive transfer of WT splenocytes into CD4-/-, CD8-/-,
      B cell-/-, and IFN-gamma-/- mice. WT mice exposed to gut I/R exhibited
      significant increases in the adhesion of both platelets and leukocytes, compared
      with sham-WT mice. These blood cell adhesion responses to I/R were greatly
      attenuated in CD4-/-, CD8-/-, B cell-/-, and IFN-gamma-/- mice. Adoptive transfer
      of WT splenocytes restored the WT responses to I/R in all mutants except the B
      cell-/- mice. These findings implicate both T and B cells and lymphocyte-derived
      IFN-gamma as mediators of the proinflammatory and prothrombogenic phenotype
      assumed by intestinal microvessels after I/R.

PMID- 19118115
TI  - Short food deprivation inhibits orexin receptor 1 expression and orexin-A induced
      intracellular calcium signaling in acutely isolated duodenal enterocytes.
AB  - Close intra-arterial infusion of the appetite regulating peptide orexin-A
      stimulates bicarbonate secretion from the duodenal mucosa. The aim of the present
      study was to elucidate the ability of orexin-A to induce intracellular calcium
      signaling in acutely isolated duodenal enterocytes. Freshly isolated clusters of
      enterocytes, obtained from rat duodenal mucosa or human duodenal biopsies, were
      loaded with fura 2-AM and mounted in a perfusion chamber. Cryptlike enterocytes
      were selected (caged), and changes in intracellular calcium concentration
      ([Ca2+]i) were evaluated by fluorescence imaging. Total RNA was extracted from
      pellets of enterocytes and reverse transcribed to cDNA, and expression of orexin
      receptors 1 and 2 (OX1R and OX2R) was measured by quantitative real-time PCR.
      Orexin-A at all concentrations tested (1-100 nM) increased [Ca2+]i in enterocytes
      isolated from continuously fed rats, and the OX1R-antagonist SB-334867 (10 nM)
      attenuated the response. The primary [Ca2+]i response was a slow increase to a
      sustained plateau persisting after orexin-A removal, and a similar response was
      observed in enterocytes from human biopsies. In contrast to orexin-A, the OX2R
      agonist (Ala11,D-Leu15)-orexin-B (1-10 nM) did not induce calcium signaling.
      There were no significant [Ca2+]i responses in enterocytes from animals food
      deprived overnight, and overnight fasting decreased (P<0.01) enterocyte OX1R as
      well as OX2R mRNA. Induction of intracellular calcium signaling in isolated
      duodenal enterocytes is thus mediated primarily by OX1R receptors. Short
      (overnight) food deprivation markedly depresses receptor expression and inhibits
      orexin-A induced increases in [Ca2+]i. Studies of enterocyte signaling and
      intestinal secretion requires particular evaluation regarding feeding status.

PMID- 19118116
TI  - Association of markers of iron stores with outcomes in patients with nondialysis
      dependent chronic kidney disease.
AB  - BACKGROUND AND OBJECTIVES: Assessments of iron stores by serum iron saturation
      ratio (ISAT) and ferritin are used to direct anemia therapy in chronic kidney
      disease (CKD) and are associated with clinical outcomes in patients on dialysis.
      The association of ISAT and ferritin with outcomes in patients with nondialysis
      dependent CKD (NDD-CKD) has not been studied. DESIGN, SETTING, PARTICIPANTS, &
      MEASUREMENTS: All-cause mortality and progression of CKD [slopes of estimated GFR
      (eGFR)] were examined in 453 men with NDD-CKD. Mortality and the composite of
      mortality and ESRD were studied in Cox models. Slopes of eGFR were examined in
      mixed-effects models. RESULTS: Lower ISAT was associated with higher mortality;
      adjusted hazard ratio [95% confidence interval (CI)] with ISAT of <12%, 13 to
      17%, and >23% versus 18 to 23%; 1.40 (0.99 to 1.98), 1.20 (0.82 to 1.76), and
      0.97 (0.67 to 1.41), P = 0.025 for trend. ISAT was also associated with steeper
      slopes of eGFR (one log-unit higher ISAT associated with a slope of -0.89
      ml/min/1.73 m(2) /yr (95% CI: -1.75, -0.02, P = 0.044). Serum ferritin level
      showed no significant association with outcomes overall, but a trend for higher
      mortality was observed in patients with a serum ferritin level >250 ng/ml.
      CONCLUSIONS: Higher ISAT is associated with lower mortality and with more
      progressive CKD. Clinical trials are needed to examine if correction of low iron
      levels can improve mortality without affecting kidney function in NDD-CKD.

PMID- 19118117
TI  - Outcomes of Staphylococcus aureus infection in hemodialysis-dependent patients.
AB  - BACKGROUND AND OBJECTIVES: Staphylococcus aureus is a leading cause of infection
      in patients with ESRD. Clinical and economic outcomes associated with S. aureus
      bacteremia and other S. aureus infections in patients with ESRD were examined.
      DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: Laboratory, clinical, and hospital
      billing data from a randomized trial of 3359 hemodialysis-dependent patients
      hospitalized with S. aureus infection in the United States whose vascular access
      type was fistula or graft and who were hospitalized with S. aureus infection to
      evaluate inpatient costs, hospital days, and mortality over 12 wk were used.
      Generalized linear regression was used to identify independent predictors of 12
      wk costs, inpatient days, and mortality. RESULTS: Of the 279 patients (8.3%) who
      developed S. aureus infection during approximately 1 yr of follow-up, 25.4% were
      treated as outpatients. Among patients for whom billing data were available, 89
      patients hospitalized with S. aureus bacteremia incurred mean 12-wk inpatient
      costs of $19,454 and 11.9 inpatient days. Among the 70 patients hospitalized with
      non-bloodstream S. aureus infections, mean inpatient costs were $19,222 and the
      mean number of inpatient days was 11.3. Twelve-week mortality was 20.2 and 15.7%
      for patients with S. aureus bloodstream and non-bloodstream infections,
      respectively. Older age was independently associated with higher risk of death
      among patients with S. aureus bacteremia and with higher inpatient costs and more
      hospital days among patients with non-bloodstream infections. CONCLUSIONS:
      Hemodialysis-dependent patients with fistula or graft access incur high costs and
      long inpatient stays when hospitalized for S. aureus infection.

PMID- 19118118
TI  - Improvement in sleep apnea during nocturnal peritoneal dialysis is associated
      with reduced airway congestion and better uremic clearance.
AB  - BACKGROUND AND OBJECTIVES: Among peritoneal dialysis (PD) patients, nocturnal PD
      (NPD) is known to improve sleep apnea compared with continuous ambulatory
      peritoneal dialysis (CAPD), but the contributing factors are unclear. DESIGN,
      SETTING, PARTICIPANTS, AND MEASUREMENTS: Thirty-eight incident ESRD patients
      underwent overnight polysomnography (PSG) during NPD and CAPD. Bioelectrical
      impedance analysis, magnetic resonance imaging of the upper airway, and urea
      kinetics (Kt/V) during sleep were measured on both occasions. RESULTS: The
      prevalence of severe sleep apnea (apnea-hypopnea index, AHI > or = 15/h) was
      21.1% during NPD, and 42.1% during CAPD. Mean AHI increased from 9.6 +/- 2.7/h
      during NPD to 21.5 +/- 4.2/h during CAPD. Both obstructive and central apnea
      worsened after conversion to CAPD. NPD achieved greater reductions in total body
      water, hydration fraction, and net ultrafiltration than CAPD during sleep.
      Overnight peritoneal Kt/V and creatinine clearance were lower after conversion.
      Both peritoneal Kt/V and peritoneal creatinine clearance correlated with AHI, as
      did their changes after conversion. Volumetric magnetic resonance imaging
      revealed reduced pharyngeal volumes and cross-sectional area, and tongue
      enlargement after conversion. CONCLUSIONS: Improvement in sleep apnea during NPD
      versus CAPD is associated with better fluid and uremic clearance and reduced
      upper airway congestion during sleep.

PMID- 19118119
TI  - Circulating bacterial-derived DNA fragments and markers of inflammation in
      chronic hemodialysis patients.
AB  - BACKGROUND AND OBJECTIVES: Bacterial-derived DNA fragments (BDNAs) have been
      shown to be present in dialysis fluid, to pass through dialyzer membranes, and to
      induce IL-6 (IL-6) in mononuclear cells. The present study aimed at assessing the
      eventual presence of BDNAs in the blood of hemodialysis (HD) patients and if this
      is associated with markers of chronic inflammation. DESIGN, SETTING,
      PARTICIPANTS, & MEASUREMENTS: Fifty-eight HD patients and 30 controls were
      included in the study. A blood sample was collected from a peripheral vein and
      from the central venous catheter (CVC) or the arteriovenous fistula (AVF) and
      examined for presence of BDNAs by 16S rRNA gene PCR amplification, bacterial
      growth, and measurement of C-reactive protein and IL-6. Thirty minutes after the
      start of HD, a sample of dialysis fluid was collected before the entry into and
      at the exit of the dialyzer and examined for presence of BDNAs. RESULTS: Controls
      had negative blood cultures and absence of blood BDNAs. All HD patients had
      negative blood cultures, but in 12 (20.7%), BDNAs were present in the whole
      blood. In five of the latter, BDNAs were also found in the dialysis fluid. C
      reactive protein serum levels (mg/L) were significantly higher in patients with
      than in those without BDNAs. Likewise, IL-6 serum levels (pg/ml) were
      significantly higher in patients with BDNA than in those without. CONCLUSIONS:
      Circulating BDNAs are associated with higher levels of C-reactive protein and IL
      6 in HD patients.

PMID- 19118121
TI  - Screening for CKD in children: a global controversy.
AB  - This review addresses the relevance of urinary screening for chronic kidney
      disease (CKD) in children. Ambiguity about screening children exists because of
      the uncertainty as to whether early detection of renal disorders in childhood
      will lead to effective interventions and reduction in the number of individuals
      who subsequently progress to ESRD. A related concern is whether the adoption of
      urinary screening programs is cost effective. The most common method that is used
      for screening children for CKD involves the measurement of spot samples of urine
      for hematuria and or proteinuria. Although mass screening is now well established
      in Japan, Taiwan, and Korea, there appears to be movement away from mass
      screening to detect CKD in children and adolescents in North America and Europe.
      In December 2007, the American Academy of Pediatrics published their latest
      recommendations, in which no urinalyses were recommended at any age during
      childhood. The second issue addressed in this review is the reporting of
      estimated glomerular filtration rates (GFR) in children by clinical laboratories.

PMID- 19118120
TI  - Design of combination angiotensin receptor blocker and angiotensin-converting
      enzyme inhibitor for treatment of diabetic nephropathy (VA NEPHRON-D).
AB  - Both angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin receptor
      blockers (ARBs) can slow the progression of diabetic nephropathy. Even with ACEI
      or ARB treatment, the proportion of patients who progress to end-stage renal
      disease (ESRD) remains high. Interventions that achieve more complete blockade of
      the renin-angiotensin system, such as combination ACEI and ARB, might be
      beneficial. This approach may decrease progression of nondiabetic kidney disease.
      In diabetic nephropathy, combination therapy decreases proteinuria, but its
      effect in slowing progression is unknown. In addition, the potential for
      hyperkalemia may limit the utility of combined therapy in this population. VA
      NEPHRON-D is a randomized, double-blind, multicenter clinical trial to assess the
      effect of combination losartan and lisinopril, compared with losartan alone, on
      the progression of kidney disease in 1850 patients with diabetes and overt
      proteinuria. The primary endpoints are time to (1) reduction in estimated GFR
      (eGFR) of > 50% (if baseline < 60 ml/min/1.73 m(2)); (2) reduction in eGFR of 30
      ml/min/1.73 m(2) (if baseline > or = 60 ml/min/1.73 m(2)); (3) progression to
      ESRD (need for dialysis, renal transplant, or eGFR < 15 ml/min/1.73 m(2)); or (4)
      death. The secondary endpoint is time to change in eGFR or ESRD. Tertiary
      endpoints are cardiovascular events, slope of change in eGFR, and change in
      albuminuria at 1 yr. Specific safety endpoints are serious hyperkalemia
      (potassium > 6 mEq/L, requiring admission, emergency room visit, or dialysis),
      all-cause mortality, and other serious adverse events. This paper discusses the
      design and key methodological issues that arose during the planning of the study.

PMID- 19118122
TI  - Modulation of excitatory synaptic transmission by Delta 9-tetrahydrocannabinol
      switches from agonist to antagonist depending on firing rate.
AB  - Delta(9)-tetrahydrocannabinol (THC), the principal psychoactive ingredient in
      marijuana, acts as a partial agonist on presynaptic cannabinoid type 1 (CB1)
      receptors to inhibit neurotransmitter release. Here, we report that THC inhibits
      excitatory neurotransmission between cultured rat hippocampal neurons in a manner
      highly sensitive to stimulus rate. THC (1 microM) inhibited excitatory
      postsynaptic currents (EPSCs) and whole-cell I(Ca) evoked at 0.1 Hz but at 0.5 Hz
      THC had little effect. The cannabinoid receptor full agonists [(R)-(+)-[2,3
      dihydro-5-methyl-3[(4-morpholinyl)methyl]pyrrolo[1,2,3-de]-1,4-benzoxazinyl]-(1
      naphthalenyl)methanone mesylate salt] (Win55212-2) (100 nM) and 2
      arachidonylglycerol (1 microM) inhibited EPSCs independent of stimulation at 0.1
      or 0.5 Hz. THC occupied CB1 receptors at 0.5 Hz, but the receptors failed to
      couple to presynaptic Ca(2+) channels. Consequently, 1 microM THC blocked the
      inhibition of EPSC amplitude by Win55212-2 when EPSCs were evoked at 0.5 Hz. A
      depolarizing prepulse to 0 mV reversed THC inhibition of I(Ca), but reversal of
      the inhibition produced by Win55212-2 required a pulse to +80 mV, suggesting that
      the voltage-dependent reversal of Gbetagamma inhibition of voltage-gated Ca(2+)
      channels accounts for the frequency-dependence of cannabinoid action. THC blocked
      depolarization-induced suppression of EPSCs evoked at 0.5 Hz, indicating that it
      inhibited retrograde endocannabinoid signaling in a frequency-dependent manner.
      Thus, THC displayed a state-dependent switching from agonist to antagonist that
      may account for its complex actions in vivo.

PMID- 19118123
TI  - Anterograde trafficking of G protein-coupled receptors: function of the C
      terminal F(X)6LL motif in export from the endoplasmic reticulum.
AB  - We have reported previously that the F(X)(6)LL motif in the C termini is
      essential for export of alpha(2B)-adrenergic (alpha(2B)-AR) and angiotensin II
      type 1 receptors (AT1Rs) from the endoplasmic reticulum (ER). Here, we further
      demonstrate that mutation of the F(X)(6)LL motif similarly abolished the cell
      surface expression of alpha(2B)-AR, AT1R, alpha(1B)-AR, and beta(2)-AR,
      suggesting that the F(X)(6)LL motif plays a general role in ER export of G
      protein-coupled receptors (GPCRs). Mutation of Phe to Val, Leu, Trp, and Tyr, and
      mutation of LL to FF and VV, markedly inhibited alpha(2B)-AR transport,
      indicating that the F(X)(6)LL function cannot be fully substituted by other
      hydrophobic residues. The structural analysis revealed that the Phe residue in
      the F(X)(6)LL motif is buried in the transmembrane domains and possibly interacts
      with Ile58 in beta(2)-AR and Val42 in alpha(2B)-AR, whereas the LL motif is
      exposed to the cytosolic space. Indeed, mutation of Ile58 in beta(2)-AR and Val42
      in alpha(2B)-AR markedly disrupted cell surface transport of the receptors. It is
      noteworthy that the Val and Ile residues are highly conserved among the GPCRs
      carrying the F(X)(6)LL motif. Furthermore, the Phe mutant exhibited a stronger
      interaction with ER chaperones and was more potently rescued by physical and
      chemical treatments than the LL mutant. These data suggest that the Phe residue
      is probably involved in folding of alpha(2B)-AR and beta(2)-AR, possibly through
      interaction with other hydrophobic residues in neighboring domains. These data
      also provide the first evidence implying crucial roles of the C termini possibly
      through modulating multiple events in anterograde trafficking of GPCRs.

PMID- 19118124
TI  - How does cyclic electron flow alleviate photoinhibition in Arabidopsis?
AB  - Cyclic electron flow (CEF) around photosystem I has a role in avoiding
      photoinhibition of photosystem II (PSII), which occurs under conditions in which
      the rate of photodamage to PSII exceeds the rate of its repair. However, the
      molecular mechanism underlying how CEF contributes to photoprotection is not yet
      well understood. We examined the effect of impairment of CEF and thermal energy
      dissipation (qE) on photoinhibition using CEF (pgr5) and qE (npq1 and npq4)
      mutants of Arabidopsis (Arabidopsis thaliana) exposed to strong light. Impairment
      of CEF by mutation of pgr5 suppressed qE and accelerated photoinhibition. We
      found that impairment of qE, by mutations of pgr5, npq1, and npq4, caused
      inhibition of the repair of photodamaged PSII at the step of the de novo
      synthesis of the D1 protein. In the presence of the chloroplast protein synthesis
      inhibitor chloramphenicol, impairment of CEF, but not impairment of qE,
      accelerated photoinhibition, and a similar effect was obtained when leaves were
      infiltrated with the protonophore nigericin. These results suggest that CEF
      dependent generation of DeltapH across the thylakoid membrane helps to alleviate
      photoinhibition by at least two different photoprotection mechanisms: one is
      linked to qE generation and prevents the inhibition of the repair of photodamaged
      PSII at the step of protein synthesis, and the other is independent of qE and
      suppresses photodamage to PSII.

PMID- 19118125
TI  - An integrated genomics approach to define niche establishment by Rhodococcus
      fascians.
AB  - Rhodococcus fascians is a Gram-positive phytopathogen that induces shooty
      hyperplasia on its hosts through the secretion of cytokinins. Global
      transcriptomics using microarrays combined with profiling of primary metabolites
      on infected Arabidopsis (Arabidopsis thaliana) plants revealed that this
      actinomycete modulated pathways to convert its host into a niche. The transcript
      data demonstrated that R. fascians leaves a very characteristic mark on
      Arabidopsis with a pronounced cytokinin response illustrated by the activation of
      cytokinin perception, signal transduction, and homeostasis. The microarray data
      further suggested active suppression of an oxidative burst during the R. fascians
      pathology, and comparison with publicly available transcript data sets implied a
      central role for auxin in the prevention of plant defense activation. Gene
      Ontology categorization of the differentially expressed genes hinted at a
      significant impact of infection on the primary metabolism of the host, which was
      confirmed by subsequent metabolite profiling. The much higher levels of sugars
      and amino acids in infected plants are presumably accessed by the bacteria as
      carbon and nitrogen sources to support epiphytic and endophytic colonization.
      Hexoses, accumulating from a significantly increased invertase activity, possibly
      inhibited the expression of photosynthesis genes and photosynthetic activity in
      infected leaves. Altogether, these changes are indicative of sink development in
      symptomatic tissues. The metabolomics data furthermore point to the possible
      occurrence of secondary signaling during the interaction, which might contribute
      to symptom development. These data are placed in the context of regulation of
      bacterial virulence gene expression, suppression of defense, infection phenotype,
      and niche establishment.

PMID- 19118126
TI  - Eternal youth, the fate of developing Arabidopsis leaves upon Rhodococcus
      fascians infection.
AB  - The phytopathogenic actinomycete Rhodococcus fascians induces neoplastic shooty
      outgrowths on infected hosts. Upon R. fascians infection of Arabidopsis
      (Arabidopsis thaliana), leaves are formed with small narrow lamina and serrated
      margins. These symptomatic leaves exhibit reduced tissue differentiation, display
      more but smaller cells that do not endoreduplicate, and accumulate in the G1
      phase of the cell cycle. Together, these features imply that leaf growth occurs
      primarily through mitotic cell division and not via cell expansion. Molecular
      analysis revealed that cell cycle gene expression is activated continuously
      throughout symptomatic leaf development, ensuring persistent mitotic cycling and
      inhibition of cell cycle exit. The transition at the two major cell cycle
      checkpoints is stimulated as a direct consequence of the R. fascians signals. The
      extremely reduced phenotypical response of a cyclind3;1-3 triple knockout mutant
      indicates that the D-type cyclin/retinoblastoma/E2F transcription factor pathway,
      as a major mediator of cell growth and cell cycle progression, plays a key role
      in symptom development and is instrumental for the sustained G1-to-S and G2-to-M
      transitions during symptomatic leaf growth.

PMID- 19118128
TI  - What do motor "recovery" and "compensation" mean in patients following stroke?
AB  - There is a lack of consistency among researchers and clinicians in the use of
      terminology that describes changes in motor ability following neurological
      injury. Specifically, the terms and definitions of motor compensation and motor
      recovery have been used in different ways, which is a potential barrier to
      interdisciplinary communication. This Point of View describes the problem and
      offers a solution in the form of definitions of compensation and recovery at the
      neuronal, motor performance, and functional levels within the framework of the
      International Classification of Functioning model.

PMID- 19118127
TI  - Highly diversified molecular evolution of downstream transcription start sites in
      rice and Arabidopsis.
AB  - Alternative usage of transcription start sites (TSSs) is one of the key
      mechanisms to generate gene variation in eukaryotes. Here, we show diversified
      molecular evolution of TSSs in remotely related flowering plants, rice (Oryza
      sativa) and Arabidopsis (Arabidopsis thaliana), by comprehensive analyses of
      large collections of full-length cDNAs and genome sequences. We determined 45,917
      representative TSSs within 23,445 loci of rice and 35,313 TSSs within 16,964 loci
      of Arabidopsis, about two TSSs per locus in either species. The nucleotide
      features around TSSs displayed distinct patterns when the most upstream TSSs were
      compared with downstream TSSs. We found that CG-skew and AT-skew were clearly
      different between upstream and downstream TSSs, and that this difference was
      commonly observed in rice and Arabidopsis. Relative entropy analysis revealed
      that the most upstream TSSs had retained canonical cis elements, whereas
      downstream TSSs showed atypical nucleotide features. Expression patterns were
      distinguishable between upstream and downstream TSSs. These results indicate that
      plant TSSs were generally diversified in downstream regions, resulting in the
      development of new gene expression patterns. Furthermore, our comparative
      analysis of TSS variation between the species showed a positive correlation
      between TSS number and gene conservation. Rice and Arabidopsis might have evolved
      novel TSSs in an independent manner, which led to diversification of these two
      species.

PMID- 19118129
TI  - Is visuospatial hemineglect really a determinant of postural control following
      stroke? An acute-phase study.
AB  - OBJECTIVE: The purpose of this study was to determine the independent
      contribution of visuospatial hemineglect to impaired postural control in the
      acute phase (<2 weeks) of stroke compared with other possible clinical and
      biological determinants. METHODS: This study was conducted in 4 hospitals in the
      mid-east region of the Netherlands. A total of 78 consecutive patients with a
      first-ever acute supratentorial stroke was included. Functional balance was
      measured with the Trunk Impairment Scale, the Trunk Control Test, the Berg
      Balance Scale, and the Functional Ambulation Categories. Visuospatial hemineglect
      was assessed by means of an asymmetry index obtained from the Behavioral
      Inattention Test. The Motricity Index, vibration threshold, sustained attention,
      and the presence of hemianopia were registered as other possible clinical
      determinants. Stepwise backward multiple linear regression analysis was performed
      introducing all selected clinical determinants as well as age and poststroke time
      as possible biological determinants. RESULTS: Hemineglect was present in 17
      patients (21.8%). The groups with and without hemineglect were different for
      gender and the proportion of right hemisphere strokes, but not for age, type of
      stroke, or poststroke time. Neglect patients had on average lower scores on all
      functional balance tests as well as on the clinical assessments. Multivariate
      linear regression showed that, besides hemineglect, only muscle strength and age
      independently contributed to impaired balance explaining 65% to 72% of variance
      of the selected outcomes. CONCLUSION: This study showed that hemineglect
      independently contributes to impaired postural control in the acute phase of
      stroke.

PMID- 19118130
TI  - Effects of constraint-induced therapy versus bilateral arm training on motor
      performance, daily functions, and quality of life in stroke survivors.
AB  - BACKGROUND AND OBJECTIVE: This study investigated the relative effects of
      distributed constraint-induced therapy (CIT) and bilateral arm training (BAT) on
      motor performance, daily function, functional use of the affected arm, and
      quality of life in patients with hemiparetic stroke. METHODS: A total of 60
      patients were randomized to distributed CIT, BAT, or a control intervention of
      less specific but active therapy. Each group received intensive training for 2
      hours/day, 5 days/week, for 3 weeks. Pretreatment and posttreatment measures
      included the Fugl-Meyer Assessment (FMA), Functional Independence Measure (FIM),
      Motor Activity Log (MAL), and Stroke Impact Scale (SIS). The proximal and distal
      scores of FMA were used to examine separate upper limb (UL) elements of movement.
      RESULTS: The distributed CIT and BAT groups showed better performance in the
      overall and the distal part score of the FMA than the control group. The BAT
      group exhibited greater gains in the proximal part score of the FMA than the
      distributed CIT and control groups. Enhanced performance was found for the
      distributed CIT group in the MAL, the subtest of locomotion in the FIM, and
      certain domains of the SIS (eg, ADL/IADL). CONCLUSION: BAT may uniquely improve
      proximal UL motor impairment. In contrast, distributed CIT may produce greater
      functional gains for the affected UL in subjects with mild to moderate chronic
      hemiparesis.

PMID- 19118131
TI  - Plasticity of the attentional network after brain injury and cognitive
      rehabilitation.
AB  - BACKGROUND: This study aimed to delineate the cerebral attentional network in
      patients with traumatic brain injury (TBI) and assess for adaptations in this
      network in response to a rehabilitation intervention. METHODS: Seventeen patients
      with TBI and 15 healthy subjects underwent functional magnetic resonance imaging
      (fMRI) using a visuospatial attention task. Ten TBI patients who successfully
      completed attentional training had a follow-up fMRI. RESULTS: In the TBI
      patients, fMRI analysis showed more activation in the frontal and temporoparietal
      lobes, as well as less activation in the anterior cingulated gyrus, SMA, and
      temporooccipital regions compared to the healthy subjects. Following cognitive
      training, the TBI patients improved performance of attention tasks accompanied by
      changes in attentional network activation; the activity of the frontal lobe
      decreased, whereas activation of the anterior cingulate cortices and precuneus
      increased. CONCLUSIONS: These findings demonstrate the plasticity and training
      induced redistribution of the visuospatial attentional network in TBI patients.

PMID- 19118132
TI  - Multidrug resistance protein 2-mediated estradiol-17beta-D-glucuronide transport
      potentiation: in vitro-in vivo correlation and species specificity.
AB  - Multidrug resistance protein 2 (MRP2) is a multispecific organic anion
      transporter expressed at important pharmacological barriers, including the
      canalicular membrane of hepatocytes. At this location it is involved in the
      elimination of both endogenous and exogenous waste products, mostly as
      conjugates, to the bile. Estradiol-17beta-d-glucuronide (E(2)17betaG), a widely
      studied endogenous substrate of MRP2, was shown earlier to recognize two binding
      sites of the transporter in vesicular transport assays. MRP2 modulators
      (substrates and nonsubstrates) potentiate the transport of E(2)17betaG by MRP2.
      We correlated data obtained from studies of different complexities and
      investigated the species-specific differences between rat and human MRP2-mediated
      transport. We used vesicular transport assays, sandwich-cultured primary
      hepatocytes, and in vivo biliary efflux in rats. Our results demonstrate that the
      rat Mrp2 transporter, unlike the human MRP2, transports E(2)17betaG according to
      Michaelis-Menten type kinetics. Nevertheless, in the presence of modulator drugs
      E(2)17betaG transport mediated by the rat transporter also shows cooperative
      kinetics as potentiation of E(2)17betaG transport was observed in the vesicular
      transport assay. We also demonstrated that the potentiation exists both in rat
      and in human hepatocytes and in vivo in rats.

PMID- 19118133
TI  - Vascular perfused segments of human intestine as a tool for drug absorption.
AB  - Blood-based vascular perfusion of isolated segments of human jejunum was
      developed as a tool for drug absorption studies before clinical trials.
      Acceptance criteria for viable human gut preparations included stable blood flow,
      arterial pressure, glucose utilization, active peristalsis, oxygen uptake, less
      than 3% absorption of a 70,000 mol. wt. dextran, and a ratio of first-order
      absorption rate constants (k(a)) of antipyrine to terbutaline of > or =1.4.
      Mannitol absorption was less than that of antipyrine but larger than that of
      terbutaline and could not be used as a negative control in absorption studies
      with human intestine. In separate perfusions (n = 3) a cassette of nine drugs was
      administered into the gut lumen, and the net absorption of each drug into the
      circulation was measured over 75 min. Using the mean values of k(a), the test
      compounds could be ranked into four groups: group 1: sulfasalazine and
      furosemide, k(a) = 3.9 to 4.0 x 10(-3) min(-1); group 2: cimetidine, timolol,
      nadolol, and ranitidine, k(a) = 6.4 to 8.3 x 10(-3) min(-1); group 3: atenolol
      and metoprolol, k(a) = 9.6 x 10(-3) min(-1); and group 4: theophylline, k(a) =
      17.5 x 10(-3) min(-1). The rationale for evaluating yet another oral absorption
      system was as follows: first, a human gut segment with an intact vascular system
      is the closest system available to a clinical trial without performing one; and
      second, the data generated would be a direct measure of net drug transport from
      the gut lumen into the vascular circulation under near physiological conditions,
      which is not possible in models lacking a blood supply.

PMID- 19118135
TI  - Vegetarian diets in children and adolescents.

PMID- 19118134
TI  - Synergy between enzyme inhibitors of fatty acid amide hydrolase and
      cyclooxygenase in visceral nociception.
AB  - The present study investigated whether inhibition of fatty acid amide hydrolase
      (FAAH), the enzyme responsible for anandamide catabolism, produces
      antinociception in the acetic acid-induced abdominal stretching model of visceral
      nociception. Genetic deletion or pharmacological inhibition of FAAH reduced
      acetic acid-induced abdominal stretching. Transgenic mice that express FAAH
      exclusively in the nervous system displayed the antinociceptive phenotype,
      indicating the involvement of peripheral fatty acid amides. The cannabinoid
      receptor 1 (CB(1)) receptor antagonist, rimonabant, but not the cannabinoid
      receptor 2 (CB(2)) receptor antagonist, SR144528, blocked the antinociceptive
      phenotype of FAAH(-/-) mice and the analgesic effects of URB597 (3'-carbamoyl
      biphenyl-3-yl-cyclohexylcarbamate) or OL-135 (1-oxo-1[5-(2-pyridyl)-2-yl]-7
      phenyl heptane), respective irreversible and reversible FAAH inhibitors,
      administered to C57BL/6 mice. The opioid receptor antagonist, naltrexone, did not
      block the analgesic effects of either FAAH inhibitor. URB597, ED(50) [95%
      confidence interval (CI) = 2.1 (1.5-2.9) mg/kg], and the nonselective
      cyclooxygenase inhibitor, diclofenac sodium [ED(50) (95% CI) = 9.8 (8.2-11.7)
      mg/kg], dose-dependently inhibited acetic acid-induced abdominal stretching.
      Combinations of URB597 and diclofenac yielded synergistic analgesic interactions
      according to isobolographic analysis. It is important that FAAH(-/-) mice and
      URB597-treated mice displayed significant reductions in the severity of gastric
      irritation caused by diclofenac. URB597 lost its gastroprotective effects in
      CB(1)(-/-) mice, whereas it maintained its efficacy in CB(2)(-/-) mice,
      indicating a CB(1) mechanism of action. Taken together, the results of the
      present study suggest that FAAH represents a promising target for the treatment
      of visceral pain, and a combination of FAAH inhibitors and NSAIDs may have great
      utility to treat visceral pain, with reduced gastric toxicity.

PMID- 19118137
TI  - Acute fever.

PMID- 19118138
TI  - Index of suspicion.

PMID- 19118139
TI  - Pediatrics in the community: practicing pediatrics with the meter running.

PMID- 19118140
TI  - What's new: Cervical cancer screening in adolescents.

PMID- 19118141
TI  - Visual diagnosis: A 5-year-old male who has an intensely pruritic maculopapular
      rash.

PMID- 19118142
TI  - Hematopoietic growth factors in pediatric patients.

PMID- 19118143
TI  - Care of the very low-birthweight infant.

PMID- 19118144
TI  - Cross dendritic cells anger T cells after kidney injury.

PMID- 19118145
TI  - Yin and Yang: acute kidney injury and chronic kidney disease.

PMID- 19118146
TI  - Salt in the wound.

PMID- 19118147
TI  - Targeting cyst initiation in ADPKD.

PMID- 19118148
TI  - HIF in kidney disease and development.
AB  - Tissue hypoxia is a pathologic feature of many human diseases including cancer,
      myocardial infarction, stroke, and kidney disease. An evolutionarily conserved
      oxygen-sensing mechanism enables cells to adapt and maintain homeostasis under
      hypoxic conditions by transcriptional activation of a host of genes that mediate
      metabolic adaptation, angiogenesis, energy conservation, erythropoiesis, and cell
      survival. The hypoxia-inducible factors (HIFs) comprise a family of oxygen
      sensitive basic helix-loop-helix proteins that control the cellular
      transcriptional response to hypoxia. Inappropriate activation of the HIF system
      is linked to the development and/or progression of many human malignancies
      including clear cell renal cancer. HIFs are now postulated to play contrasting
      protective and pathogenic roles in acute and chronic kidney diseases,
      respectively. In this review, we discuss the mechanisms of oxygen sensing in
      renal cells and highlight the role of hypoxia and HIF activation under
      physiologic conditions and in renal development as well as in acute and chronic
      kidney diseases.

PMID- 19118149
TI  - Impaired tubular uptake explains albuminuria in early diabetic nephropathy.
AB  - Understanding the pathogenesis of albuminuria in diabetic nephropathy is
      important to improve methods for early diagnosis and treatment. In this study, we
      addressed whether albuminuria in diabetes results from altered glomerular
      filtration and/or altered processing of filtered albumin by the proximal tubule.
      Type 1 diabetic Munich Wistar rats developed albuminuria after 12 wk of diabetes.
      Intravital two-photon microscopy revealed similar glomerular permeability in the
      diabetic and control animals, assessed using both albumin-Alexa568 and 69-kD FITC
      dextran; however, diabetic animals demonstrated significantly less filtered
      fluorescent albumin in renal proximal tubule (PT) cells compared with control
      animals. We also observed increased albumin-derived urinary peptide excretion in
      diabetic animals, and hyperglycemia modulated this peptideuria. In conclusion, in
      the early stages of diabetic nephropathy, the PT plays a major role in the
      development of albuminuria, which may be preceded by peptideuria.

PMID- 19118150
TI  - Pregnancy and the kidney.
AB  - Nephrologists are frequently called on to diagnose and treat renal disorders in
      pregnant women. In this review, we update recent literature pertinent to
      pregnancy and renal disease. We initially begin by describing the application of
      common clinical estimators of GFR and proteinuria in pregnancy and then summarize
      recent studies regarding pregnancy in women with chronic kidney disease and the
      latest information on the use of common renal medications in pregnancy. In the
      final section, we describe advances in our understanding of the pathophysiology
      of preeclampsia and the potential clinical implications of these discoveries for
      screening, prevention, and treatment of preeclampsia.

PMID- 19118151
TI  - Plasma ADMA predicts restenosis of arteriovenous fistula.
AB  - Plasma levels of asymmetrical dimethylarginine (ADMA), an endogenous inhibitor of
      nitric oxide production, correlate with endothelial dysfunction and the
      development of cardiovascular events in patients with uremia. It is not known
      whether endothelial dysfunction contributes to the dysfunction of arteriovenous
      fistulas (AVFs) in hemodialysis patients. Here, we studied the predictive value
      of baseline plasma ADMA for symptomatic restenosis of an AVF after percutaneous
      transluminal angioplasty in dialysis patients. We obtained baseline plasma ADMA
      levels before percutaneous transluminal angioplasty in 100 consecutive patients
      with dysfunctional AVFs. Patients were followed up clinically for up to 6 mo
      after angioplasty for recurrent dysfunction. During the 6 mo after angioplasty,
      46 patients experienced recurrent dysfunction of their AVF; of these, follow-up
      fistulography showed restenosis at the same location in 41, new stenosis at
      different locations in two, and no significant stenosis in three patients. Up to
      60% of the patients with high levels of ADMA (>0.910 microM) had target lesion
      restenosis compared with 25% of those with low levels (<0.910 microM; P < 0.001).
      In multivariate analysis, plasma ADMA independently nearly tripled the risk for
      recurrent symptomatic stenosis of an AVF after percutaneous transluminal
      angioplasty (hazard ratio 2.65; 95% confidence interval 1.33 to 5.28). These
      results suggest a role for ADMA in the progression of symptomatic restenoses of
      AVFs after percutaneous transluminal angioplasty and call for preventive
      strategies that target ADMA and/or endothelial dysfunction to decrease the risk
      for AVF restenosis.

PMID- 19118154
TI  - Making "time" for alveolar recruitment.

PMID- 19118153
TI  - NFATc1 identifies a population of proximal tubule cell progenitors.
AB  - Recovery from acute kidney injury requires regeneration of tubule cells. Because
      calcineurin induces nuclear transport of NFATc proteins, whose expression pattern
      correlates with the nephron segments injured by calcineurin inhibitors, we
      hypothesized that NFATc1 plays a role in modifying epithelial regeneration after
      injury. To test this, we induced proximal tubular cell (PTC) injury in Balb/c
      mice and Nfatc1(+/-) mice with mercuric chloride; the PTCs of Nfatc1(+/-) mice
      demonstrated increased apoptosis, sustained injury, and delayed regeneration. To
      attenuate NFATc1 activity further, we injected cyclosporin A daily. Cyclosporin A
      treated Nfatc1(+/-) mice demonstrated rapid and severe injury after
      administration of mercuric chloride, with increased serum creatinine, increased
      apoptosis, decreased PTC proliferation, and increased mortality compared with
      similarly treated wild-type mice. Using a novel NFATc1 transgenic line that
      reports activation of an NFATc1 enhancer domain critical for NFATc1
      autoamplification, we demonstrated accentuated NFATc1 expression in a PTC
      subpopulation after mercuric chloride-induced injury. In addition, NFATc1
      labeled, apoptosis-resistant PTCs proliferated to repair the damaged proximal
      tubule segment. These data provide evidence for a resident progenitor PTC
      population and suggest a role for NFATc1 in the regeneration of injured proximal
      tubules.

PMID- 19118152
TI  - Nephronophthisis: disease mechanisms of a ciliopathy.
AB  - Nephronophthisis (NPHP), a recessive cystic kidney disease, is the most frequent
      genetic cause of end-stage kidney disease in children and young adults.
      Positional cloning of nine genes (NPHP1 through 9) and functional
      characterization of their encoded proteins (nephrocystins) have contributed to a
      unifying theory that defines cystic kidney diseases as "ciliopathies." The theory
      is based on the finding that all proteins mutated in cystic kidney diseases of
      humans or animal models are expressed in primary cilia or centrosomes of renal
      epithelial cells. Primary cilia are sensory organelles that connect
      mechanosensory, visual, and other stimuli to mechanisms of epithelial cell
      polarity and cell-cycle control. Mutations in NPHP genes cause defects in
      signaling mechanisms that involve the noncanonical Wnt signaling pathway and the
      sonic hedgehog signaling pathway, resulting in defects of planar cell polarity
      and tissue maintenance. The ciliary theory explains the multiple organ
      involvement in NPHP, which includes retinal degeneration, cerebellar hypoplasia,
      liver fibrosis, situs inversus, and mental retardation. Positional cloning of
      dozens of unknown genes that cause NPHP will elucidate further signaling
      mechanisms involved. Nephrocystins are highly conserved in evolution, thereby
      allowing the use of animal models to develop future therapeutic approaches.

PMID- 19118155
TI  - Signals of motor command bias joint position sense in the presence of feedback
      from proprioceptors.
AB  - Joint position sense is believed to be mediated by muscle afferent signals.
      Because a "phantom" hand produced by a sensory and motor nerve block appears to
      move in the direction of voluntary effort, signals of "motor command" or "effort"
      can influence perceived joint position. To determine whether this occurs when
      sensory signals are available, three studies assessed position sense when motor
      command and afferent signals were available, but joint movement was prevented.
      First, the hand was positioned to stop movement at the proximal joint of the
      middle finger, and movement at the distal joint was impossible because the
      muscles had been "disengaged". Voluntary efforts produced illusory position
      changes in the direction of the effort (12.6 +/- 2.0 degrees distal joint; 12.3
      +/- 2.3 degrees proximal joint for efforts at 30% maximum; means +/- SD). Second,
      when subjects attempted to move the index finger under isometric conditions, the
      index finger appeared to move 7.4 +/- 1.2 degrees in the direction of efforts.
      These illusions graded with the level of effort (10 or 30% maximum) and far
      exceeded any real joint movement. Finally, because changes in muscle afferent
      feedback might have accompanied the voluntary efforts, all forearm and hand
      muscles were completely paralyzed by locally infused rocuronium. During
      paralysis, passive wrist position was signaled accurately, but, during attempted
      efforts (30% maximum), perceived wrist position changed by 9.7 +/- 4.9 degrees .
      Before paralysis, isometric efforts changed it by 6.7 +/- 3.6 degrees . Thus all
      studies concur: when joint movement is prevented, signals of motor command
      contribute to joint position sense.

PMID- 19118156
TI  - Ultrasonic evaluations of Achilles tendon mechanical properties poststroke.
AB  - Spasticity, contracture, and muscle weakness are commonly observed poststroke in
      muscles crossing the ankle. However, it is not clear how biomechanical properties
      of the Achilles tendon change poststroke, which may affect functions of the
      impaired muscles directly. Biomechanical properties of the Achilles tendon,
      including the length and cross-sectional area, in the impaired and unimpaired
      sides of 10 hemiparetic stroke survivors were evaluated using ultrasonography.
      Elongation of the Achilles tendon during controlled isometric ramp-and-hold and
      ramping up then down contractions was determined using a block-matching method.
      Biomechanical changes in stiffness, Young's modulus, and hysteresis of the
      Achilles tendon poststroke were investigated by comparing the impaired and
      unimpaired sides of the 10 patients. The impaired side showed increased tendon
      length (6%; P = 0.04), decreased stiffness (43%; P < 0.001), decreased Young's
      modulus (38%; P = 0.005), and increased mechanical hysteresis (1.9 times higher;
      P < 0.001) compared with the unimpaired side, suggesting Achilles tendon
      adaptations to muscle spasticity, contracture, and/or disuse poststroke. In vivo
      quantitative characterizations of the tendon biomechanical properties may help us
      better understand changes of the calf muscle-tendon unit as a whole and
      facilitate development of more effective treatments.

PMID- 19118157
TI  - Postnatal development of metabolic rate during normoxia and acute hypoxia in
      rats: implication for a sensitive period.
AB  - Previously, we reported that the hypoxic ventilatory response (HVR) in rats was
      weakest at postnatal day (P) P13, concomitant with neurochemical changes in
      respiratory nuclei. A major determinant of minute ventilation (Ve) is reportedly
      the metabolic rate [O(2) consumption (Vo(2)) and CO(2) production (Vco(2))]. The
      present study aimed at testing our hypothesis that daily metabolic rates changed
      in parallel with ventilation during development and that a weak HVR at P13 was
      attributable mainly to an inadequate metabolic rate in hypoxia. Ventilation and
      metabolic rates were monitored daily in P0-P21 rats. We found that 1) ventilation
      and metabolic rates were not always correlated, and Ve/Vo(2) and Ve/Vco(2) ratios
      were not constant during development; 2) metabolic rate and Ve/Vo(2) and
      Ve/Vco(2) ratios at P0-P1 were significantly different from the remaining first
      postnatal week in normoxia and hypoxia; 3) at P13, metabolic rates and Ve/Vo(2)
      and Ve/Vco(2) ratios abruptly increased in normoxia and were compromised in acute
      hypoxia, unlike more stable trends during the remaining second and third
      postnatal weeks; and 4) the respiratory quotient (Vco(2)/Vo(2)) was quite stable
      in normoxia and fluctuated slightly in hypoxia from P0 to P21. Thus our data
      revealed heretofore unsuspected metabolic adjustments at P0-P1 and P13. At P0-P1,
      ventilation and metabolic rates were uncorrelated, whereas at P13, they were
      closely correlated under normoxia and hypoxia. The findings further strengthened
      the existence of a critical period of respiratory development around P13, when
      multiple physiological and neurochemical adjustments occur simultaneously.

PMID- 19118159
TI  - Optic nerve sheath diameter correlates with the presence and severity of acute
      mountain sickness: evidence for increased intracranial pressure.
AB  - Increased intracranial pressure is suspected in the pathogenesis of acute
      mountain sickness (AMS), but no studies have correlated it with the presence or
      severity of AMS. We sought to determine whether increased optic nerve sheath
      diameter, a surrogate measure of intracranial pressure, is associated with the
      presence and severity of AMS. We performed a cross-sectional study of travelers
      ascending through Pheriche, Nepal (4,240 m), from March 3 to May 14, 2006. AMS
      was assessed using the Lake Louise score. Optic nerve sheath diameter was
      measured by ultrasound. Ultrasound exams were performed and read by separate
      blinded observers. Two-hundred eighty seven subjects were enrolled. Ten of these
      underwent repeat examination. Mean optic nerve sheath diameter was 5.34 mm [95%
      confidence interval (CI) 5.18-5.51 mm] in the 69 subjects with AMS vs. 4.46 mm
      (95% CI 4.39-4.54 mm) in the 218 other subjects (P < 0.0001). There was also a
      positive association between optic nerve sheath diameter and total Lake Louise
      score (P for trend < 0.0001). In a multivariate logistic regression model of
      factors associated with AMS, optic nerve sheath diameter was strongly associated
      with AMS (odds ratio 6.3; 95% CI, 3.7-10.8; P < 0.001). In 10 subjects with
      repeat examinations, change in Lake Louise score had a strong positive
      correlation with change in optic nerve sheath diameter (R(2) = 0.84, P < 0.001).
      Optic nerve sheath diameter, a proxy for intracranial pressure, is associated
      with the presence and severity of AMS.

PMID- 19118158
TI  - Influence of cerebral blood flow on breathing stability.
AB  - Our previous work showed a diminished cerebral blood flow (CBF) response to
      changes in Pa(CO(2)) in congestive heart failure patients with central sleep
      apnea compared with those without apnea. Since the regulation of CBF serves to
      minimize oscillations in H(+) and Pco(2) at the site of the central
      chemoreceptors, it may play an important role in maintaining breathing stability.
      We hypothesized that an attenuated cerebrovascular reactivity to changes in
      Pa(CO(2)) would narrow the difference between the eupneic Pa(CO(2)) and the
      apneic threshold Pa(CO(2)) (DeltaPa(CO(2))), known as the CO(2) reserve, thereby
      making the subjects more susceptible to apnea. Accordingly, in seven normal
      subjects, we used indomethacin (Indo; 100 mg by mouth) sufficient to reduce the
      CBF response to CO(2) by approximately 25% below control. The CO(2) reserve was
      estimated during non-rapid eye movement (NREM) sleep. The apnea threshold was
      determined, both with and without Indo, in NREM sleep, in a random order using a
      ventilator in pressure support mode to gradually reduce Pa(CO(2)) until apnea
      occurred. results: Indo significantly reduced the CO(2) reserve required to
      produce apnea from 6.3 +/- 0.5 to 4.4 +/- 0.7 mmHg (P = 0.01) and increased the
      slope of the ventilation decrease in response to hypocapnic inhibition below
      eupnea (control vs. Indo: 1.06 +/- 0.10 vs. 1.61 +/- 0.27 l x min(-1) x mmHg(-1),
      P < 0.05). We conclude that reductions in the normal cerebral vascular response
      to hypocapnia will increase the susceptibility to apneas and breathing
      instability during sleep.

PMID- 19118160
TI  - Dissecting the functions of protein-protein interactions: caveolin as a
      promiscuous partner. Focus on "Caveolin-1 scaffold domain interacts with TRPC1
      and IP3R3 to regulate Ca2+ store release-induced Ca2+ entry in endothelial
      cells".

PMID- 19118161
TI  - Podocalyxin-like protein is an E-/L-selectin ligand on colon carcinoma cells:
      comparative biochemical properties of selectin ligands in host and tumor cells.
AB  - Selectins facilitate metastasis and tumor cell arrest in the microvasculature by
      mediating binding of selectin-expressing host cells to ligands on tumor cells. We
      recently identified CD44 variant isoforms as functional P-, but not E-/L-,
      selectin ligands on colon carcinoma cells. Furthermore, a approximately 180-kDa
      sialofucosylated glycoprotein(s) mediated selectin binding in CD44-knockdown
      cells. Using immunoaffinity chromatography and tandem mass spectrometry, we
      identify podocalyxin-like protein (PCLP) as an alternative selectin ligand. Blot
      rolling and cell-free flow-based adhesion assays disclose that PCLP on LS174T
      colon carcinoma cells possesses E-/L-, but not P-, selectin binding activity. The
      selectin-binding determinants on LS174T PCLP are non-MECA-79-reactive
      sialofucosylated structures displayed on O-linked glycans, distinct from the MECA
      79-reactive O-glycans on PCLP expressed by high endothelial venules, which is an
      L-selectin ligand. PCLP on CD44-knockdown LS174T cells exhibits higher HECA-452
      immunoreactivity than PCLP on wild-type cells, suggesting that PCLP functions as
      an alternative acceptor for selectin-binding glycans. The enhanced expression of
      HECA-452 reactivity on PCLP from CD44-knockdown cells correlates with the
      increased avidity of PCLP for E- but not L-selectin. The novel finding that PCLP
      is an E-/L-selectin ligand on carcinoma cells offers a unifying perspective on
      the apparent enhanced metastatic potential associated with tumor cell PCLP
      overexpression and the role of selectins in metastasis.

PMID- 19118163
TI  - VASP is involved in cAMP-mediated Rac 1 activation in microvascular endothelial
      cells.
AB  - Accumulating evidence points to a significant role of vasodilator-stimulated
      phosphoprotein (VASP) in the maintenance of endothelial barrier functions. We
      have recently shown that impaired barrier functions in VASP-deficient
      microvascular myocardial endothelial cells (MyEnd VASP(-/-)) correlated with
      decreased Rac 1 activity. To further test the hypothesis that VASP is involved in
      regulation of Rac 1 activity, we studied cAMP-dependent Rac 1 activation. Both
      inhibition of Rac 1 activation by NSC-23766 and inhibition of PKA by PKI
      completely blunted the efficacy of forskolin/rolipram (F/R)-mediated cAMP
      increase to stabilize barrier functions as revealed by measurements of
      transendothelial resistance (TER). Because these results indicate that PKA/Rac 1
      activation is important for barrier stabilization, we tested this signaling
      pathway in VASP(-/-) cells. We found that F/R and isoproterenol reduced
      permeability measured as FITC-dextran flux across VASP(-/-) monolayers, but not
      below baseline levels of wild-type cells (WT). Moreover, cAMP-mediated Rac 1
      activation was reduced to approximately 50% of WT levels, and both PKA inhibition
      by PKI and PKA anchoring via A kinase anchoring peptides (AKAPs) by HT31 almost
      completely abolished Rac 1 activation in VASP(-/-) and WT endothelium.
      Accordingly, HT31 significantly reduced F/R-mediated TER increase in WT cells and
      completely blocked the protective effect of cAMP on endothelial barrier
      properties. Together, our data underline the significant role of cAMP-mediated
      Rac 1 activation for endothelial barrier stabilization and demonstrate that both
      AKAP-mediated PKA anchoring and VASP are required for this process.

PMID- 19118162
TI  - Nox4 NADPH oxidase mediates oxidative stress and apoptosis caused by TNF-alpha in
      cerebral vascular endothelial cells.
AB  - Inflammatory brain disease may damage cerebral vascular endothelium leading to
      cerebral blood flow dysregulation. The proinflammatory cytokine TNF-alpha causes
      oxidative stress and apoptosis in cerebral microvascular endothelial cells
      (CMVEC) from newborn pigs. We investigated contribution of major cellular sources
      of reactive oxygen species to endothelial inflammatory response. Nitric oxide
      synthase and xanthine oxidase inhibitors (N(omega)-nitro-l-arginine and
      allopurinol) had no effect, while mitochondrial electron transport inhibitors
      (CCCP, 2-thenoyltrifluoroacetone, and rotenone) attenuated TNF-alpha-induced
      superoxide (O(2)(*-)) and apoptosis. NADPH oxidase inhibitors (diphenylene
      iodonium and apocynin) greatly reduced TNF-alpha-evoked O(2)(*-) generation and
      apoptosis. TNF-alpha rapidly increased NADPH oxidase activity in CMVEC. Nox4, the
      cell-specific catalytic subunit of NADPH oxidase, is highly expressed in CMVEC,
      contributes to basal O(2)(*-) production, and accounts for a burst of oxidative
      stress in response to TNF-alpha. Nox4 small interfering RNA, but not Nox2,
      knockdown prevented oxidative stress and apoptosis caused by TNF-alpha in CMVEC.
      Nox4 is colocalized with HO-2, the constitutive isoform of heme oxygenase (HO),
      which is critical for endothelial protection against TNF-alpha toxicity. The
      products of HO activity, bilirubin and carbon monoxide (CO, as a CO-releasing
      molecule, CORM-A1), inhibited Nox4-generated O(2)(*-) and apoptosis caused by TNF
      alpha stimulation. We conclude that Nox4 is the primary source of inflammation-
      and TNF-alpha-induced oxidative stress leading to apoptosis in brain endothelial
      cells. The ability of CO and bilirubin to combat TNF-alpha-induced oxidative
      stress by inhibiting Nox4 activity and/or by O(2)(*-) scavenging, taken together
      with close intracellular compartmentalization of HO-2 and Nox4 in cerebral
      vascular endothelium, may contribute to HO-2 cytoprotection against inflammatory
      cerebrovascular disease.

PMID- 19118164
TI  - Nardilysin convertase regulates the function of the maxi-K channel isoform mK44
      in human myometrium.
AB  - In smooth muscle, large-conductance Ca(2+)- and voltage-activated K(+) channels
      from the gene KCNMA (maxi-K channels) generate isoforms with disparate responses
      to contractile stimuli. We previously showed that the human myometrium expresses
      high levels of the splice variant of the maxi-K channel containing a 44-amino
      acid insertion (mK44). The studies presented here demonstrate that nardilysin
      convertase, a Zn(2+)-dependent metalloprotease of the insulinase family,
      regulates the plasma membrane expression of mK44 and its response to increases in
      intracellular Ca(2+). We show that nardilysin convertase isoform 1 is present in
      human myometrium and colocalizes with mK44. Studies indicate that nardilysin
      convertase regulates 1) retention of the mK44 COOH-terminal fragment in the
      endoplasmic reticulum in quiescent myometrial smooth muscle and 2) Ca(2+)-induced
      translocation of mK44 to the plasma membrane. In mouse fibroblasts, nardilysin
      convertase significantly attenuates mK44-dependent current. In human myometrial
      smooth muscle cells, inhibition of nardilysin convertase promotes membrane
      localization of mK44 and an increase in maxi-K current. Overall, our data
      indicate that, in human myometrium, nardilysin convertase and mK44 channels are a
      part of the molecular mechanism that regulates the excitability of smooth muscle
      cells.

PMID- 19118165
TI  - Cell-type-dependent molecular composition of the axon initial segment.
AB  - The exact site of initiation and shape of action potentials vary among different
      neuronal types. The reason for this variability is largely unknown, but the
      subunit composition, density and distribution of voltage-gated sodium (Nav) and
      potassium (Kv) channels within the axon initial segment (AIS) are likely to play
      a key role. Here, we asked how heterogeneous are the density and distribution of
      Nav and Kv channels within the AISs of a variety of excitatory and inhibitory
      neurons. Most of the studied cell types expressed a high density of Nav1.6,
      Kv1.1, and Kv1.2 subunits in their AIS, but the Nav1.1 subunit could only be
      detected in GABAergic interneurons. A proximo-distal gradient in the density of
      these subunits was observed within the AIS of certain nerve cells but not in
      others. For example, a gradual increase of the Nav1.6 subunit was observed in
      cortical layer 2/3 and hippocampal CA1 pyramidal cell (PC) AISs, whereas its
      density was rather uniform in layer 5 PC AISs. The Nav1.1 subunit was distributed
      evenly along the AIS of short-axon cells of the main olfactory bulb but was
      restricted to the proximal part of the AIS in cortical and cerebellar
      interneurons. Our results reveal a cell type-dependent expression of sodium and
      potassium channel subunits with varying densities along the proximo-distal axis
      of the AISs. This precise arrangement is likely to contribute to the diversity of
      firing properties observed among central neurons.

PMID- 19118166
TI  - The bifunctional microRNA miR-9/miR-9* regulates REST and CoREST and is
      downregulated in Huntington's disease.
AB  - The transcription factor REST silences neuronal gene expression in non-neuronal
      cells. In neurons, the protein is sequestered in the cytoplasm in part through
      binding to huntingtin. Polyglutamine expansions in huntingtin, which causes
      Huntington's disease (HD), abrogates REST-huntingtin binding. Consequently, REST
      translocates to the nucleus, occupies RE1 repressor sequences and decreases
      neuronal gene expression. In this work, we found that levels of several microRNAs
      (miRNAs) with upstream RE1 sites are decreased in HD patient cortices relative to
      healthy controls. Interestingly, one of these, the bifunctional brain enriched
      miR-9/miR-9*, targets two components of the REST complex: miR-9 targets REST and
      miR-9* targets CoREST. These data provide evidence for a double negative feedback
      loop between the REST silencing complex and the miRNAs it regulates.

PMID- 19118168
TI  - Differential cAMP signaling at hippocampal output synapses.
AB  - cAMP is a critical second messenger involved in synaptic transmission and
      synaptic plasticity. Here, we show that activation of the adenylyl cyclase by
      forskolin and application of the cAMP-analog Sp-5,6-DCl-cBIMPS both mimicked and
      occluded tetanus-induced long-term potentiation (LTP) in subicular bursting
      neurons, but not in subicular regular firing cells. Furthermore, LTP in bursting
      cells was inhibited by protein kinase A (PKA) inhibitors Rp-8-CPT-cAMP and H-89.
      Variations in the degree of EPSC blockade by the low-affinity competitive AMPA
      receptor-antagonist gamma-d-glutamyl-glycine (gamma-DGG), analysis of the
      coefficient of variance as well as changes in short-term potentiation suggest an
      increase of glutamate concentration in the synaptic cleft after expression of
      LTP. We conclude that presynaptic LTP in bursting cells requires activation of
      PKA by a calcium-dependent adenylyl cyclase while LTP in regular firing cells is
      independent of elevated cAMP levels. Our results provide evidence for a
      differential role of cAMP in LTP at hippocampal output synapses.

PMID- 19118167
TI  - Stimulus-induced changes in blood flow and 2-deoxyglucose uptake dissociate in
      ipsilateral somatosensory cortex.
AB  - The present study addresses the relationship between blood flow and glucose
      consumption in rat primary somatosensory cortex (SI) in vivo. We examined
      bilateral neuronal and hemodynamic changes and 2-deoxyglucose (2DG) uptake, as
      measured by autoradiography, in response to unilateral forepaw stimulation. In
      contrast to the contralateral forepaw area, where neuronal activity, blood
      oxygenation/flow and 2DG uptake increased in unison, we observed, in the
      ipsilateral SI, a blood oxygenation/flow decrease and arteriolar vasoconstriction
      in the presence of increased 2DG uptake. Laminar electrophysiological recordings
      revealed an increase in ipsilateral spiking consistent with the observed increase
      in 2DG uptake. The vasoconstriction and the decrease in blood flow in the
      presence of an increase in 2DG uptake in the ipsilateral SI contradict the
      prominent metabolic hypothesis regarding the regulation of cerebral blood flow,
      which postulates that the state of neuroglial energy consumption determines the
      regional blood flow through the production of vasoactive metabolites. We propose
      that other factors, such as neuronal (and glial) release of messenger molecules,
      might play a dominant role in the regulation of blood flow in vivo in response to
      a physiological stimulus.

PMID- 19118169
TI  - RTP801 is induced in Parkinson's disease and mediates neuron death by inhibiting
      Akt phosphorylation/activation.
AB  - Previously, we reported that RTP801, a stress regulated protein, is induced in
      multiple cellular models of Parkinson's disease (PD), in an animal model of PD
      and in dopaminergic neurons of PD patients. In cellular PD models, RTP801 is both
      sufficient and necessary for death. We further showed that RTP801 and PD mimetics
      such as 6-OHDA trigger neuron death by suppressing activation of the key kinase
      mammalian target of rapamycin (mTOR). Here, we report that as a consequence of
      mTOR signaling blockade, 6-OHDA suppresses the phosphorylation and activation of
      Akt, a major supporter of neuron survival. This effect is mediated by RTP801 and
      appears to underlie neuron death induced by 6-OHDA. Examination of postmortem
      dopaminergic neurons reveals a consistent depletion of phospho-Akt, but not of
      total Akt in PD patients. These observations support a sequential mechanism in
      which PD-associated stresses induce RTP801, suppress mTOR signaling, deplete
      phosphorylated/activated Akt and permit neuron degeneration and death.

PMID- 19118170
TI  - Midbrain dopamine receptor availability is inversely associated with novelty
      seeking traits in humans.
AB  - Novelty-seeking personality traits are a major risk factor for the development of
      drug abuse and other unsafe behaviors. Rodent models of temperament indicate that
      high novelty responding is associated with decreased inhibitory autoreceptor
      control of midbrain dopamine neurons. It has been speculated that individual
      differences in dopamine functioning also underlie the personality trait of
      novelty seeking in humans. However, differences in the dopamine system of rodents
      and humans, as well as the methods for assessing novelty responding/seeking
      across species leave unclear to what extent the animal models inform our
      understanding of human personality. In the present study we examined the
      correlation between novelty-seeking traits in humans and D(2)-like (D(2)/D(3))
      receptor availability in the substantia nigra/ventral tegmental area. Based on
      the rodent literature we predicted that novelty seeking would be characterized by
      lowered levels of D(2)-like (auto)receptor availability in the midbrain. Thirty
      four healthy adults (18 men, 16 women) completed the Tridimensional Personality
      Questionnaire-Novelty-Seeking Scale and PET scanning with the D(2)/D(3) ligand
      [(18)F]fallypride. Novelty-Seeking personality traits were inversely associated
      with D(2)-like receptor availability in the ventral midbrain, an effect that
      remained significant after controlling for age. We speculate that the lower
      midbrain (auto)receptor availability seen in high novelty seekers leads to
      accentuated dopaminergic responses to novelty and other conditions that induce
      dopamine release.

PMID- 19118171
TI  - Bursicon functions within the Drosophila CNS to modulate wing expansion behavior,
      hormone secretion, and cell death.
AB  - Hormones are often responsible for synchronizing somatic physiological changes
      with changes in behavior. Ecdysis (i.e., the shedding of the exoskeleton) in
      insects has served as a useful model for elucidating the molecular and cellular
      mechanisms of this synchronization, and has provided numerous insights into the
      hormonal coordination of body and behavior. An example in which the mechanisms
      have remained enigmatic is the neurohormone bursicon, which, after the final
      molt, coordinates the plasticization and tanning of the initially folded wings
      with behaviors that drive wing expansion. The somatic effects of the hormone are
      governed by bursicon that is released into the blood from neurons in the
      abdominal ganglion (the B(AG)), which die after wing expansion. How bursicon
      induces the behavioral programs required for wing expansion, however, has
      remained unknown. Here we show by targeted suppression of excitability that a
      pair of bursicon-immunoreactive neurons distinct from the B(AG) and located
      within the subesophageal ganglion in Drosophila (the B(SEG)) is involved in
      controlling wing expansion behaviors. Unlike the B(AG), the B(SEG) arborize
      widely in the nervous system, including within the abdominal neuromeres,
      suggesting that, in addition to governing behavior, they also may modulate the
      B(AG.) Indeed, we show that animals lacking bursicon receptor function have
      deficits both in the humoral release of bursicon and in posteclosion apoptosis of
      the B(AG). Our results reveal novel neuromodulatory functions for bursicon and
      support the hypothesis that the B(SEG) are essential for orchestrating both the
      behavioral and somatic processes underlying wing expansion.

PMID- 19118173
TI  - Cytoplasmic inclusions of Htt exon1 containing an expanded polyglutamine tract
      suppress execution of apoptosis in sympathetic neurons.
AB  - Proteins containing extended polyglutamine repeats cause at least nine
      neurodegenerative disorders, but the mechanisms of disease-related neuronal death
      remain uncertain. We show that sympathetic neurons containing cytoplasmic
      inclusions formed by 97 glutamines expressed within human huntingtin exon1
      enhanced green fluorescent protein (Q97) undergo a protracted form of
      nonapoptotic death that is insensitive to Bax deletion or caspase inhibition but
      is characterized by mitochondrial dysfunction. By treating the neurons with
      combined cytosine arabinoside and NGF withdrawal, we demonstrate that Q97 confers
      a powerful resistance to apoptosis at multiple levels: despite normal
      proapoptotic signaling (elevation of P-ser15-p53 and BimEL), there is no increase
      of Puma mRNA or Bax activation, both necessary for apoptosis. Even restoration of
      Bax translocation with overexpressed Puma does not activate apoptosis. We
      demonstrate that this robust inhibition of apoptosis is caused by Q97-mediated
      accumulation of Hsp70, which occurs through inhibition of proteasomal activity.
      Thus, apoptosis is reinstated by short hairpin RNA-mediated knockdown of Hsp70.
      These findings explain the rarity of apoptotic death in Q97-expressing neurons.
      Given the proteasomal blockade, we test whether enhancing lysosomal-mediated
      degradation with rapamycin reduces Q97 accumulation. Rapamycin reduces the amount
      of nonpathological Q25 by 70% over 3 d, but Q97 accumulation is unaffected.
      Interestingly, Q47 inclusions form more slowly as a result of constitutive
      lysosomal degradation, but faster-forming Q97 inclusions escape lysosomal
      control. Thus, cytoplasmic Q97 inclusions are refractory to clearance by
      proteasomal and lysosomal systems, leading to a toxicity that dominates over
      neuroprotective Hsp70. Our findings may explain the rarity of apoptosis but the
      inevitable cell death associated with polyQ inclusion diseases.

PMID- 19118172
TI  - Deletion of Mint proteins decreases amyloid production in transgenic mouse models
      of Alzheimer's disease.
AB  - Mints/X11s are neuronal adaptor proteins that bind to amyloid-beta precursor
      protein (APP). Previous studies suggested that Mint/X11 proteins influence APP
      cleavage and affect production of pathogenic amyloid-beta (Abeta) peptides in
      Alzheimer's disease; however, the biological significance of Mint/X11 binding to
      APP and their possible role in Abeta production remain unclear. Here, we crossed
      conditional and constitutive Mint1, Mint2, and Mint3 knock-out mice with
      transgenic mouse models of Alzheimer's disease overproducing human Abeta
      peptides. We show that deletion of all three individual Mint proteins delays the
      age-dependent production of amyloid plaque numbers and Abeta40 and Abeta42 levels
      with loss of Mint2 having the largest effect. Acute conditional deletion of all
      three Mints in cultured neurons suppresses the accumulation of APP C-terminal
      fragments and the secretion of ectodomain APP by decreasing beta-cleavage but
      does not impair subsequent gamma-cleavage. These results suggest that the three
      Mint/X11 proteins regulate Abeta production by a novel mechanism that may have
      implications for therapeutic approaches to altering APP cleavage in Alzheimer's
      disease.

PMID- 19118174
TI  - Encoding human sexual chemosensory cues in the orbitofrontal and fusiform
      cortices.
AB  - Chemosensory communication of affect and motivation is ubiquitous among animals.
      In humans, emotional expressions are naturally associated with faces and voices.
      Whether chemical signals play a role as well has hardly been addressed. Here, we
      use functional magnetic resonance imaging to show that the right orbitofrontal
      cortex, right fusiform cortex, and right hypothalamus respond to airborne natural
      human sexual sweat, indicating that this particular chemosensory compound is
      encoded holistically in the brain. Our findings provide neural evidence that
      socioemotional meanings, including the sexual ones, are conveyed in the human
      sweat.

PMID- 19118175
TI  - Transcranial magnetic stimulation to the frontal operculum and supramarginal
      gyrus disrupts planning of outcome-based hand-object interactions.
AB  - Behavioral data suggest that goals inform the selection of motor commands during
      planning. We investigated the neural correlates that mediate planning of goal
      oriented actions by asking 10 healthy subjects to prepare either a goal-specific
      movement toward a common object (a cup), with the intent of grasping-to-pour
      (liquid into it) or grasping-to-move (to another location) the object, or
      performing a non-object-oriented stimulus-response task (move a finger). Single
      pulse transcranial magnetic stimulation was administered on 50% of trials to the
      supramarginal gyrus (SMG), anterior intraparietal sulcus, inferior frontal gyrus
      opercularis (IFGo), and triangularis during motor planning. Stimulation to SMG
      and IFGo caused a significant delay in planning goal-oriented actions but not
      responses to an arbitrary stimulus. Despite the delay, movement execution was not
      affected, suggesting that the motor plan remained intact. Our data implicate the
      SMG and IFGo in planning goal-oriented hand-object interactions.

PMID- 19118176
TI  - A common single nucleotide polymorphism alters the synthesis and secretion of
      neuropeptide Y.
AB  - A single nucleotide polymorphism (SNP) in the neuropeptide Y gene has been
      associated with elevated serum lipid levels and cardiovascular disease. The
      polymorphism (T1128C) changes the seventh amino acid in the prohormone from
      leucine to proline. It has been speculated this alters neuropeptide Y (NPY)
      synthesis, trafficking, or secretion. We tested this hypothesis by expressing the
      mutant and wild-type prohormones in CNS neurons and endocrine cells. Synthesis
      and trafficking were followed using immunocytochemistry and fluorescent protein
      tagged fusion constructs. Mutant prohormone was synthesized and entered the
      regulated secretory pathway. When expressed in endocrine cells, wild-type and
      mutant proteins were found in the same large dense core granules. However, the
      T1128C polymorphism altered the degree of copackaging, and, on average,
      individual granules contained more mutant prohormone. This was not attributable
      to codon bias but to the change in prohormone sequence. Global prohormone
      targeting was normal, because in hippocampal neurons, the polarized distribution
      of the mutant prohormone was indistinguishable from the wild-type. When secretion
      was measured from chromaffin cells, brief depolarizations triggered peptide
      secretion, confirming the entry of the mutant prohormone into the regulated
      secretory pathway. However, cells that expressed the mutant protein had increased
      levels of peptide secretion. We conclude that the T1128C polymorphism alters the
      packaging and secretion of NPY. In contrast to SNPs in other prohormones, we
      could not find a phenotype until the prohormone was tracked at the single granule
      level. These results are consistent with studies showing the T1128C polymorphism
      has pleiotropic effects.

PMID- 19118177
TI  - Electrical coupling of lobula plate tangential cells to a heterolateral motion
      sensitive neuron in the fly.
AB  - Many motion-sensitive tangential cells of the lobula plate in blowflies are well
      described with respect to their visual response properties and the connectivity
      among them. In addition to extensive connections between tangential cells within
      the lobula plate of one brain hemisphere, there exist many connections between
      the two hemispheres. Most of these connections have been found for neurons
      sensitive to horizontal motion. For neurons sensitive to vertical motion,
      however, only the connection of vertical sensitive cells (VS cells) and a cell
      (V1 cell) projecting to the other hemisphere has been demonstrated thus far. The
      ability to identify the presynaptic and postsynaptic cells as well as the good
      accessibility has made this specific synapse a model for graded transmission of
      synapses. However, the exact type of synapse, electrical or chemical, is not
      known. Investigating the connectivity between VS cells 1-3 and the V1 cell by
      means of dual recordings, we find that the VS cells are coupled via electrical
      synapses to the V1 cell. The results were confirmed by visualizing dye coupling
      between VS cells and V1.

PMID- 19118178
TI  - Spred1 is required for synaptic plasticity and hippocampus-dependent learning.
AB  - Germline mutations in SPRED1, a negative regulator of Ras, have been described in
      a neurofibromatosis type 1 (NF1)-like syndrome (NFLS) that included learning
      difficulties in some affected individuals. NFLS belongs to the group of
      phenotypically overlapping neuro-cardio-facial-cutaneous syndromes that are all
      caused by germ line mutations in genes of the Ras/mitogen-activated protein
      kinase extracellular signal-regulated kinase (ERK) pathway and that present with
      some degree of learning difficulties or mental retardation. We investigated
      hippocampus-dependent learning and memory as well as synaptic plasticity in
      Spred1(-/-) mice, an animal model of this newly discovered human syndrome.
      Spred1(-/-) mice show decreased learning and memory performance in the Morris
      water maze and visual-discrimination T-maze, but normal basic neuromotor and
      sensory abilities. Electrophysiological recordings on brain slices from these
      animals identified defects in short- and long-term synaptic hippocampal
      plasticity, including a disequilibrium between long-term potentiation (LTP) and
      long-term depression in CA1 region. Biochemical analysis, 4 h after LTP
      induction, demonstrated increased ERK-phosphorylation in Spred1(-/-) slices
      compared with those of wild-type littermates. This indicates that deficits in
      hippocampus-dependent learning and synaptic plasticity induced by SPRED1
      deficiency are related to hyperactivation of the Ras/ERK pathway.

PMID- 19118179
TI  - Synaptic vesicles in mature calyx of Held synapses sense higher nanodomain
      calcium concentrations during action potential-evoked glutamate release.
AB  - During development of the calyx of Held synapse, presynaptic action potentials
      (APs) become substantially faster and briefer. Nevertheless, this synapse is able
      to upregulate quantal output triggered by arriving APs. Briefer APs lead to less
      effective gating of voltage-gated Ca(2+) channels (VGCCs). Therefore, mechanisms
      downstream of Ca(2+) entry must effectively compensate for the attenuated Ca(2+)
      influx associated with shorter APs in more mature calyces. This compensation
      could be achieved by tighter spatial coupling between VGCCs and synaptic
      vesicles, so that the latter are exposed to higher intracellular Ca(2+)
      concentration ([Ca(2+)](i)). Alternatively or additionally, the Ca(2+)
      sensitivity of the release apparatus may increase during synapse development. To
      differentiate between these possibilities, we combined paired patch-clamp
      recordings with Ca(2+) imaging and flash photolysis of caged Ca(2+) and estimated
      the [Ca(2+)](i) requirements for vesicle release in the developing mouse calyx of
      Held synapse. Surprisingly, the dose-response relationship between [Ca(2+)](i)
      and release rate was shifted slightly to the right in more mature calyces,
      rendering their vesicles slightly less sensitive to incoming Ca(2+). Taking into
      account the time course and peak rates of AP-evoked release transients for the
      corresponding developmental stages, we estimate the local [Ca(2+)](i)"seen" by
      the Ca(2+) sensors on synaptic vesicles to increase from 35 to 56 mum [from
      postnatal day 9 (P9)-P11 to P16-P19]. Our results reinforce the idea that
      developmental tightening of the spatial coupling between VGCCs and synaptic
      vesicles plays a predominant role in enhancing quantal output at this synapse and
      possibly other central synapses.

PMID- 19118180
TI  - Neural dissociation of delay and uncertainty in intertemporal choice.
AB  - Decision makers often face choices whose consequences unfold over time. To
      explore the neural basis of such intertemporal choice behavior, we devised a
      novel two-alternative choice task with probabilistic reward delivery and
      contrasted two conditions that differed only in whether the outcome was revealed
      immediately or after some delay. In the immediate condition, we simply varied the
      reward probability of each option and the outcome was revealed immediately. In
      the delay condition, the outcome was revealed after a delay during which the
      reward probability was governed by a constant hazard rate. Functional imaging
      revealed a set of brain regions, such as the posterior cingulate cortex,
      parahippocampal gyri, and frontal pole, that exhibited activity uniquely
      associated with the temporal aspects of the task. This engagement of the so
      called "default network" suggests that during intertemporal choice, decision
      makers simulate the impending delay via a process of prospection.

PMID- 19118182
TI  - Ongoing activity fluctuations in hMT+ bias the perception of coherent visual
      motion.
AB  - We have recently shown that intrinsic fluctuations of ongoing activity during
      baseline have an impact on perceptual decisions reported for an ambiguous visual
      stimulus (Hesselmann et al., 2008). To test whether this result generalizes from
      the visual object domain to other perceptual and neural systems, the current
      study investigated the effect of ongoing signal fluctuations in motion-sensitive
      brain regions on the perception of coherent visual motion. We determined motion
      coherence thresholds individually for each subject using a dynamic random dot
      display. During functional magnetic resonance imaging (fMRI), brief events of
      subliminal, supraliminal, and periliminal coherent motion were presented with
      long and variable interstimulus intervals between them. On each trial, subjects
      reported whether they had perceived "coherent" or "random" motion, and fMRI
      signal time courses were analyzed separately as a function of stimulus and
      percept type. In the right motion-sensitive occipito-temporal cortex (hMT+),
      coherent percepts of periliminal stimuli yielded a larger stimulus-evoked
      response than random percepts. Prestimulus baseline activity in this region was
      also significantly higher in these coherent trials than in random trials. As in
      our previous study, however, the relation between ongoing and evoked activity was
      not additive but interacted with perceptual outcome. Our data thus suggest that
      endogenous fluctuations in baseline activity have a generic effect on subsequent
      perceptual decisions. Although mainstream analytical techniques used in
      functional neuroimaging do not capture this nonadditive effect of baseline on
      evoked response, it is in accord with postulates from theoretical frameworks as,
      for instance, predictive coding.

PMID- 19118181
TI  - Sensory responses during sleep in primate primary and secondary auditory cortex.
AB  - Most sensory stimuli do not reach conscious perception during sleep. It has been
      thought that the thalamus prevents the relay of sensory information to cortex
      during sleep, but the consequences for cortical responses to sensory signals in
      this physiological state remain unclear. We recorded from two auditory cortical
      areas downstream of the thalamus in naturally sleeping marmoset monkeys. Single
      neurons in primary auditory cortex either increased or decreased their responses
      during sleep compared with wakefulness. In lateral belt, a secondary auditory
      cortical area, the response modulation was also bidirectional and showed no clear
      systematic depressive effect of sleep. When averaged across neurons, sound-evoked
      activity in these two auditory cortical areas was surprisingly well preserved
      during sleep. Neural responses to acoustic stimulation were present during both
      slow-wave and rapid-eye movement sleep, were repeatedly observed over multiple
      sleep cycles, and demonstrated similar discharge patterns to the responses
      recorded during wakefulness in the same neuron. Our results suggest that the
      thalamus is not as effective a gate for the flow of sensory information as
      previously thought. At the cortical stage, a novel pattern of
      activation/deactivation appears across neurons. Because the neural signal reaches
      as far as secondary auditory cortex, this leaves open the possibility of altered
      sensory processing of auditory information during sleep.

PMID- 19118183
TI  - NMDA- and beta-amyloid1-42-induced neurotoxicity is attenuated in serine racemase
      knock-out mice.
AB  - D-Serine is detected in the brain and acts as a coagonist at the "glycine-site"
      of the NMDA-type glutamate receptor. Although D-serine can be directly produced
      from L-serine by serine racemase (SR), the relative contribution of SR in D
      serine formation in vivo is not known. Pathological roles of brain D-serine
      mediating NMDA receptor overactivation are suggested in studies using in vitro
      culture systems. However, we have recently demonstrated the differential SR
      protein expression in vivo and in culture. Here, we reported an approximately 90%
      decrease in forebrain D-serine content in SR knock-out (KO) mice. We also found a
      reduced neurotoxicity induced by NMDA- and Abeta(1-42)- peptide injections into
      the forebrain in SR KO mice. These results suggest that SR is the major enzyme
      for D-serine production in the brain, D-serine is the predominant endogenous
      coagonist of the NMDA receptor in the forebrain, and D-serine may be involved in
      controlling the extent of NMDA receptor-mediated neurotoxic insults observed in
      disorders including Alzheimer's disease. The control of SR activity and D-serine
      level in the brain may lead to a novel strategy for neuroprotection against
      various neurodegenerative diseases.

PMID- 19118184
TI  - Neurogenic and neuroendocrine effects of goldfish pheromones.
AB  - Goldfish (Carassius auratus) use reproductive hormones as endocrine signals to
      synchronize sexual behavior with gamete maturation and as exogenous signals
      (pheromones) to mediate spawning interactions between conspecifics. We examined
      the differential effects of two hormonal pheromones, prostaglandin F(2alpha)
      (PGF(2alpha)) and 17alpha,20beta-dihydroxy-4-pregnen-3-one (17,20beta-P) on
      neurogenesis, neurotransmission, and neuronal activities, and on plasma
      androstenedione (AD) levels. Exposure to waterborne PGF(2alpha) induced a
      multitude of changes in male goldfish brain. Histological examination indicated
      an increase in the number of dividing cells in male diencephalon (p < 0.05,
      Kruskal-Wallis test). Real-time quantitative PCR tests showed elevated levels of
      transcripts for the salmon gonadotropin-releasing hormone (GnRH) in the male
      telencephalon and cerebellum (p < 0.005, one-way ANOVA) and for ChAT (choline
      acetyltransferase) in the male vagal lobe and the brainstem underneath the vagal
      lobe (p < 0.05, one-way ANOVA). Therefore, PGF(2alpha) seemed to modulate male
      brain plasticity that coincided with behavioral changes during spawning season.
      Exposure to waterborne 17,20beta-P, however, increased circulatory levels of
      immunoreactive AD in males and the transcripts of androgen receptor and cGnRH-II
      (chicken-II GnRH) in the female cerebellum (p < 0.05, one-way ANOVA). PGF(2alpha)
      and 17,20beta-P thereby seemed to act through distinct pathways to elicit
      different responses in the neuroendocrine system. This is the first finding that
      links a specific pheromone molecule (PGF(2alpha)) to neurogenesis in a vertebrate
      animal.

PMID- 19118185
TI  - Loss-of-function analysis suggests that Omi/HtrA2 is not an essential component
      of the PINK1/PARKIN pathway in vivo.
AB  - Recently, a mutation in the mitochondrial protease Omi/HtrA2, G399S, was found in
      sporadic Parkinson's disease (PD) patients, leading to the designation of
      Omi/HtrA2 as PD locus 13 (PARK13). G399S reportedly results in reduced Omi
      protease activity. In vitro studies have suggested that Omi/HtrA2 acts downstream
      of PINK1, mutations in which mediate recessive forms of PD. We, as well as other,
      have previously shown that the Drosophila homologs of the familial PD genes,
      PINK1 (PARK6) and PARKIN (PARK2), function in a common genetic pathway to
      regulate mitochondrial integrity and dynamics. Whether Omi/HtrA2 regulates
      mitochondrial integrity and whether it acts downstream of PINK1 in vivo remain to
      be explored. Here, we show that Omi/HtrA2 null mutants in Drosophila, in contrast
      to pink1 or parkin null mutants, do not show mitochondrial morphological defects.
      Extensive genetic interaction studies do not provide support for models in which
      Omi/HtrA2 functions in the same genetic pathway as pink1, or carries out
      partially redundant functions with pink1, at least with respect to regulation of
      mitochondrial integrity and dynamics. Furthermore, Omi/HtrA2 G399S retains
      significant, if not full, function of Omi/HtrA2, compared with expression of
      protease-compromised versions of the protein. In light of recent findings showing
      that G399S can be found at comparable frequencies in PD patients and healthy
      controls, we do not favor a hypothesis in which Omi/HtrA2 plays an essential role
      in PD pathogenesis, at least with respect to regulation of mitochondrial
      integrity in the pink1/parkin pathway.

PMID- 19118186
TI  - Spatial learning impairment, enhanced CDK5/p35 activity, and downregulation of
      NMDA receptor expression in transgenic mice expressing tau-tubulin kinase 1.
AB  - Tau-tubulin kinase-1 (TTBK1) is involved in phosphorylation of tau protein at
      specific Serine/Threonine residues found in paired helical filaments, suggesting
      its role in tauopathy pathogenesis. We found that TTBK1 levels were upregulated
      in brains of human Alzheimer' disease (AD) patients compared with age-matched non
      AD controls. To understand the effects of TTBK1 activation in vivo, we developed
      transgenic mice harboring human full-length TTBK1 genomic DNA (TTBK1-Tg).
      Transgenic TTBK1 is highly expressed in subiculum and cortical pyramidal layers,
      and induces phosphorylated neurofilament aggregation. TTBK1-Tg mice show
      significant age-dependent memory impairment as determined by radial arm water
      maze test, which is associated with enhancement of tau and neurofilament
      phosphorylation, increased levels of p25 and p35, both activators of cyclin
      dependent protein kinase 5 (CDK5), enhanced calpain I activity, and reduced
      levels of hippocampal NMDA receptor types 2B (NR2B) and D. Enhanced CDK5/p35
      complex formation is strongly correlated with dissociation of F-actin from p35,
      suggesting the inhibitory mechanism of CDK5/p35 complex formation by F-actin.
      Expression of recombinant TTBK1 in primary mouse cortical neurons significantly
      downregulated NR2B in a CDK5- and calpain-dependent manner. These data suggest
      that TTBK1 in AD brain may be one of the underlying mechanisms inducing CDK5 and
      calpain activation, NR2B downregulation, and subsequent memory dysfunction.

PMID- 19118187
TI  - Enhanced adult neurogenesis and angiogenesis and altered affective behaviors in
      mice overexpressing vascular endothelial growth factor 120.
AB  - Vascular endothelial growth factor (VEGF) is implicated as a molecular mediator
      for adult neurogenesis and behavioral effects of antidepressant drugs. However,
      these potential roles of VEGF in the CNS have not been clarified in model
      animals. Here we have created transgenic mice overexpressing a short active
      variant of VEGF-A (VEGF120) in forebrain. Expression of VEGF120 significantly
      enhanced cell proliferation and angiogenesis, as exemplified by the formation of
      an enlarged reddish brain. Adult neurogenesis in hippocampus was markedly
      stimulated without affecting cell differentiation of neural progenitor cells.
      Hippocampal neurogenesis was particularly robust in young adult animals, but it
      declined with age and reduced to control levels by 20 weeks under continuous
      expression of VEGF120. Thus, VEGF alone is not sufficient to support the long
      term enhancement of adult neurogenesis, and VEGF-induced vascularization per se
      does not necessarily predict increased neurogenesis. In transgenic mice, we
      observed significant changes in affective behaviors. VEGF was found to have not
      only antidepressant effects but also anxiolytic effects. In addition, we found
      that VEGF significantly reduced fear and aggression. In contrast, basal
      activities under natural conditions were not affected much. Unexpectedly, these
      characteristic behaviors were maintained in older transgenic mice undergoing a
      reduced level of cell proliferation in hippocampus, suggesting that there is
      potential dissociation between adult neurogenesis and mood regulation. Our data
      indicate that VEGF exerts strong neurogenic and angiogenic effects in postnatal
      brain and influences different forms of affective behaviors.

PMID- 19118189
TI  - Preso, a novel PSD-95-interacting FERM and PDZ domain protein that regulates
      dendritic spine morphogenesis.
AB  - PSD-95 is an abundant postsynaptic density (PSD) protein involved in the
      formation and regulation of excitatory synapses and dendritic spines, but the
      underlying mechanisms are not comprehensively understood. Here we report a novel
      PSD-95-interacting protein Preso that regulates spine morphogenesis. Preso is
      mainly expressed in the brain and contains WW (domain with two conserved Trp
      residues), PDZ (PSD-95/Dlg/ZO-1), FERM (4.1, ezrin, radixin, and moesin), and C
      terminal PDZ-binding domains. These domains associate with actin filaments, the
      Rac1/Cdc42 guanine nucleotide exchange factor betaPix, phosphatidylinositol-4,5
      bisphosphate, and the postsynaptic scaffolding protein PSD-95, respectively.
      Preso overexpression increases the density of dendritic spines in a manner
      requiring WW, PDZ, FERM, and PDZ-binding domains. Conversely, knockdown or
      dominant-negative inhibition of Preso decreases spine density, excitatory
      synaptic transmission, and the spine level of filamentous actin. These results
      suggest that Preso positively regulates spine density through its interaction
      with the synaptic plasma membrane, actin filaments, PSD-95, and the betaPix-based
      Rac1 signaling pathway.

PMID- 19118188
TI  - Picomolar amyloid-beta positively modulates synaptic plasticity and memory in
      hippocampus.
AB  - Amyloid-beta (Abeta) peptides are produced in high amounts during Alzheimer's
      disease, causing synaptic and memory dysfunction. However, they are also released
      in lower amounts in normal brains throughout life during synaptic activity. Here
      we show that low picomolar concentrations of a preparation containing both
      Abeta(42) monomers and oligomers cause a marked increase of hippocampal long-term
      potentiation, whereas high nanomolar concentrations lead to the well established
      reduction of potentiation. Picomolar levels of Abeta(42) also produce a
      pronounced enhancement of both reference and contextual fear memory. The
      mechanism of action of picomolar Abeta(42) on both synaptic plasticity and memory
      involves alpha7-containing nicotinic acetylcholine receptors. These findings
      strongly support a model for Abeta effects in which low concentrations play a
      novel positive, modulatory role on neurotransmission and memory, whereas high
      concentrations play the well known detrimental effect culminating in dementia.

PMID- 19118190
TI  - Validation of multivariate model of leaf ionome is fundamentally confounded.

PMID- 19118191
TI  - Constraining the loop, releasing prion infectivity.

PMID- 19118192
TI  - Continuous elimination of oxidized nucleotides is necessary to prevent rapid
      onset of cellular senescence.
AB  - Reactive oxygen species (ROS) appear to play a role in limiting both cellular and
      organismic lifespan. However, because of their pleiotropic effects, it has been
      difficult to ascribe a specific role to ROS in initiating the process of cellular
      senescence. We have studied the effects of oxidative DNA damage on cell
      proliferation, believing that such damage is of central importance to triggering
      senescence. To do so, we devised a strategy to decouple levels of 8-oxoguanine, a
      major oxidative DNA lesion, from ROS levels. Suppression of MTH1 expression,
      which hydrolyzes 8-oxo-dGTP, was accompanied by increased total cellular 8
      oxoguanine levels and caused early-passage primary and telomerase-immortalized
      human skin fibroblasts to rapidly undergo senescence, doing so without altering
      cellular ROS levels. This senescent phenotype recapitulated several salient
      features of replicative senescence, notably the presence of senescence-associated
      beta-galactosidase (SA beta-gal) activity, apparently irreparable genomic DNA
      breaks, and elevation of p21(Cip1), p53, and p16(INK4A) tumor suppressor protein
      levels. Culturing cells under low oxygen tension (3%) largely prevented the
      shMTH1-dependent senescent phenotype. These results indicate that the nucleotide
      pool is a critical target of intracellular ROS and that oxidized nucleotides,
      unless continuously eliminated, can rapidly induce cell senescence through
      signaling pathways very similar to those activated during replicative senescence.

PMID- 19118193
TI  - Teaching Cre to follow directions.

PMID- 19118194
TI  - Localizing interference during naming: convergent neuroimaging and
      neuropsychological evidence for the function of Broca's area.
AB  - To produce a word, the intended word must be selected from a competing set of
      other words. In other domains where competition affects the selection process,
      the left inferior frontal gyrus (LIFG) responds to competition among incompatible
      representations. The aim of this study was to test whether the LIFG is necessary
      for resolution of competition in word production. Using a methodological approach
      applying the same rigorous analytic methods to neuropsychological data as is done
      with neuroimaging data, we compared brain activation patterns in normal speakers
      (using fMRI) with the results of lesion-deficit correlations in aphasic speakers
      who performed the same word production task designed to elicit competition during
      lexical selection. The degree of activation of the LIFG in normal speakers and
      damage to the LIFG in aphasic speakers was associated with performance on the
      production task. These convergent findings provide strong support for the
      hypothesis that the region of cortex commonly known as Broca's area (i.e., the
      posterior LIFG) serves to bias competitive interactions during language
      production.

PMID- 19118195
TI  - On the fate of anthropogenic nitrogen.
AB  - This article provides a synthesis of literature values to trace the fate of 150
      Tg/yr anthropogenic nitrogen applied by humans to the Earth's land surface.
      Approximately 9 TgN/yr may be accumulating in the terrestrial biosphere in pools
      with residence times of ten to several hundred years. Enhanced fluvial transport
      of nitrogen in rivers and percolation to groundwater accounts for approximately
      35 and 15 TgN/yr, respectively. Greater denitrification in terrestrial soils and
      wetlands may account for the loss of approximately 17 TgN/yr from the land
      surface, calculated by a compilation of data on the fraction of N(2)O emitted to
      the atmosphere and the current global rise of this gas in the atmosphere. A
      recent estimate of atmospheric transport of reactive nitrogen from land to sea
      (NO(x) and NH(x)) accounts for 48 TgN/yr. The total of these enhanced sinks, 124
      TgN/yr, is less than the human-enhanced inputs to the land surface, indicating
      areas of needed additional attention to global nitrogen biogeochemistry. Policy
      makers should focus on increasing nitrogen-use efficiency in fertilization,
      reducing transport of reactive N to rivers and groundwater, and maximizing
      denitrification to its N(2) endproduct.

PMID- 19118196
TI  - Combined targeting of lentiviral vectors and positioning of transduced cells by
      magnetic nanoparticles.
AB  - Targeting of viral vectors is a major challenge for in vivo gene delivery,
      especially after intravascular application. In addition, targeting of the
      endothelium itself would be of importance for gene-based therapies of vascular
      disease. Here, we used magnetic nanoparticles (MNPs) to combine cell transduction
      and positioning in the vascular system under clinically relevant, nonpermissive
      conditions, including hydrodynamic forces and hypothermia. The use of MNPs
      enhanced transduction efficiency of endothelial cells and enabled direct
      endothelial targeting of lentiviral vectors (LVs) by magnetic force, even in
      perfused vessels. In addition, application of external magnetic fields to mice
      significantly changed LV/MNP biodistribution in vivo. LV/MNP-transduced cells
      exhibited superparamagnetic behavior as measured by magnetorelaxometry, and they
      were efficiently retained by magnetic fields. The magnetic interactions were
      strong enough to position MNP-containing endothelial cells at the intima of
      vessels under physiological flow conditions. Importantly, magnetic positioning of
      MNP-labeled cells was also achieved in vivo in an injury model of the mouse
      carotid artery. Intravascular gene targeting can be combined with positioning of
      the transduced cells via nanomagnetic particles, thereby combining gene- and cell
      based therapies.

PMID- 19118197
TI  - Structural basis for selectin mechanochemistry.
AB  - Selectins are adhesion molecules that resist large tensile forces applied by
      hydrodynamic forces to leukocytes binding to vessel walls. In crystals, the
      liganded (high-affinity) and unliganded (low-affinity) conformations differ in
      orientation between their tandem lectin and EGF domains. I examine how tensile
      force exerted on a selectin-ligand complex in vivo could favor the more extended,
      high-affinity conformation. Allostery is transmitted from the EGF-lectin domain
      interface to the ligand-binding interface on the lectin domain, 30 A away. Trp-1
      of the lectin domain and the long axis of the EGF domain form an L-shaped prybar
      that is welded together by hydrogen bonds to the Trp-1 alpha-amino group.
      Pivoting of the prybar induced by force demolishes an interface between the Trp-1
      side chain and the lectin domain at a switch1 region. These changes are
      transmitted by rigid body movement of the switch2 region to rearrangements in the
      switch3 region at the ligand binding site. Another switch region corresponds to a
      single residue in the EGF domain with large effects on ligand binding and rolling
      adhesion. Allostery in selectins, and the alignment of tensile force on a
      selectin-ligand complex with the transition pathway for conformational change,
      explain much of the structural basis for selectin mechanochemistry.

PMID- 19118198
TI  - Neuronal activity regulates phosphorylation-dependent surface delivery of G
      protein-activated inwardly rectifying potassium channels.
AB  - G protein-activated inwardly rectifying K(+) (GIRK) channels regulate neuronal
      excitability by mediating inhibitory effects of G protein-coupled receptors for
      neurotransmitters and neuromodulators. Notwithstanding many studies reporting
      modulation of GIRK channel function, whether neuronal activity regulates GIRK
      channel trafficking remains an open question. Here we report that NMDA receptor
      activation in cultured dissociated hippocampal neurons elevates surface
      expression of the GIRK channel subunits GIRK1 and GIRK2 in the soma, dendrites,
      and dendritic spines within 15 min. This activity-induced increase in GIRK
      surface expression requires protein phosphatase-1-mediated dephosphorylation of a
      serine residue (Ser-9) preceding the GIRK2 Val-13/Leu-14 (VL) internalization
      motif, thereby promoting channel recycling. Because activation of GIRK channels
      hyperpolarizes neuronal membranes, the NMDA receptor-induced regulation of GIRK
      channel trafficking may represent a dynamic adjustment of neuronal excitability
      in response to inhibitory neurotransmitters and/or neuromodulators.

PMID- 19118199
TI  - G protein-activated inwardly rectifying potassium channels mediate depotentiation
      of long-term potentiation.
AB  - Excitatory synapses in the brain undergo activity-dependent changes in the
      strength of synaptic transmission. Such synaptic plasticity as exemplified by
      long-term potentiation (LTP) is considered a cellular correlate of learning and
      memory. The presence of G protein-activated inwardly rectifying K(+) (GIRK)
      channels near excitatory synapses on dendritic spines suggests their possible
      involvement in synaptic plasticity. However, whether activity-dependent
      regulation of GIRK channels affects excitatory synaptic plasticity is unknown. In
      a companion article we have reported activity-dependent regulation of GIRK
      channel density in cultured hippocampal neurons that requires activity of NMDA
      receptors (NMDAR) and protein phosphatase-1 (PP1) and takes place within 15 min.
      In this study, we performed whole-cell recordings of cultured hippocampal neurons
      and found that NMDAR activation increases basal GIRK current and GIRK channel
      activation mediated by adenosine A(1) receptors, but not GABA(B) receptors. Given
      the similar involvement of NMDARs, adenosine A(1) receptors, and PP1 in
      depotentiation of LTP caused by low-frequency stimulation that immediately
      follows LTP-inducing high-frequency stimulation, we wondered whether NMDAR
      induced increase in GIRK channel surface density and current may contribute to
      the molecular mechanisms underlying this specific depotentiation. Remarkably,
      GIRK2 null mutation or GIRK channel blockade abolishes depotentiation of LTP,
      demonstrating that GIRK channels are critical for depotentiation, one form of
      excitatory synaptic plasticity.

PMID- 19118200
TI  - ChIP-on-chip significance analysis reveals large-scale binding and regulation by
      human transcription factor oncogenes.
AB  - ChIP-on-chip has emerged as a powerful tool to dissect the complex network of
      regulatory interactions between transcription factors and their targets. However,
      most ChIP-on-chip analysis methods use conservative approaches aimed at
      minimizing false-positive transcription factor targets. We present a model with
      improved sensitivity in detecting binding events from ChIP-on-chip data. Its
      application to human T cells, followed by extensive biochemical validation,
      reveals that 3 oncogenic transcription factors, NOTCH1, MYC, and HES1, bind to
      several thousand target gene promoters, up to an order of magnitude increase over
      conventional analysis methods. Gene expression profiling upon NOTCH1 inhibition
      shows broad-scale functional regulation across the entire range of predicted
      target genes, establishing a closer link between occupancy and regulation.
      Finally, the increased sensitivity reveals a combinatorial regulatory program in
      which MYC cobinds to virtually all NOTCH1-bound promoters. Overall, these results
      suggest an unappreciated complexity of transcriptional regulatory networks and
      highlight the fundamental importance of genome-scale analysis to represent
      transcriptional programs.

PMID- 19118201
TI  - Microbe hunting in the 21st century.

PMID- 19118202
TI  - Transmission of allostery through the lectin domain in selectin-mediated cell
      adhesion.
AB  - The selectins are cell adhesion proteins that must resist applied forces to
      mediate leukocyte tethering and rolling along the endothelium and have 2
      conformational states. Selectin-ligand bond dissociation increases only modestly
      with applied force, and exhibits catch bond behavior in a low-force regime where
      bond lifetimes counterintuitively increase with increasing force. Both allosteric
      and sliding-rebinding models have emerged to explain catch bonds. Here, we
      introduce a large residue into a cleft that opens within the lectin domain to
      stabilize the more extended, high-affinity selectin conformation. This mutation
      stabilizes the high-affinity state, but surprisingly makes rolling less stable.
      The position of the mutation in the lectin domain provides evidence for an
      allosteric pathway through the lectin domain, connecting changes at the lectin
      EGF interface to the distal binding interface.

PMID- 19118203
TI  - The specificity of T cell regulation that enables self-nonself discrimination in
      the periphery.
AB  - It was recently shown that perceiving the avidity of T cell activation can be
      translated into peripheral T cell regulation to control autoimmune disease. This
      regulation is achieved by CD8(+) T cells that recognize a common surrogate target
      structure, Qa-1/Hsp60sp, preferentially expressed by activated T cells of
      intermediate but not high avidity. A truncated self-reactive repertoire, devoid
      of high-avidity T cells, generated by thymic negative selection, allows selective
      down-regulation of intermediate-avidity T cells to accomplish self-nonself
      discrimination in the periphery. Identification of the common surrogate target
      structure expressed on intermediate-avidity T cells opens up a conceptual theme
      to understand the relationship between the specificity of peripheral immune
      regulation and self-nonself discrimination. Here, we investigated peptide
      vaccination induced cross-protection mediated by CD8(+) T cells in two autoimmune
      disease models, experimental allergic encephalomyelitis (EAE) and type 1 diabetes
      (T1D). We show that Qa-1 restricted CD8(+) T cells cross-protect animals from
      either EAE or T1D without abrogating the immune response to foreign antigens.
      Cross-protection occurs because potentially pathogenic self-reactive T cells
      included in the pool of intermediate-avidity T cells are capable of
      preferentially expressing common surrogate target structures on their surface to
      render themselves subject to the down-regulation, independent of the specificity
      of the antigens that they are triggered by. Thus, like in the thymus, the immune
      system discriminates self from nonself, during adaptive immunity in the
      periphery, not by recognizing the structural differences between self and foreign
      antigens, but rather by perceiving the avidity of T cell activation.

PMID- 19118204
TI  - Dynamics of one-state downhill protein folding.
AB  - The small helical protein BBL has been shown to fold and unfold in the absence of
      a free energy barrier according to a battery of quantitative criteria in
      equilibrium experiments, including probe-dependent equilibrium unfolding, complex
      coupling between denaturing agents, characteristic DSC thermogram, gradual
      melting of secondary structure, and heterogeneous atom-by-atom unfolding
      behaviors spanning the entire unfolding process. Here, we present the results of
      nanosecond T-jump experiments probing backbone structure by IR and end-to-end
      distance by FRET. The folding dynamics observed with these two probes are both
      exponential with common relaxation times but have large differences in amplitude
      following their probe-dependent equilibrium unfolding. The quantitative analysis
      of amplitude and relaxation time data for both probes shows that BBL folding
      dynamics are fully consistent with the one-state folding scenario and
      incompatible with alternative models involving one or several barrier crossing
      events. At 333 K, the relaxation time for BBL is 1.3 micros, in agreement with
      previous folding speed limit estimates. However, late folding events at room
      temperature are an order of magnitude slower (20 micros), indicating a relatively
      rough underlying energy landscape. Our results in BBL expose the dynamic features
      of one-state folding and chart the intrinsic time-scales for conformational
      motions along the folding process. Interestingly, the simple self-averaging
      folding dynamics of BBL are the exact dynamic properties required in molecular
      rheostats, thus supporting a biological role for one-state folding.

PMID- 19118205
TI  - Can neurosphere production help restore inner ear transduction?

PMID- 19118206
TI  - Integrin special issue.

PMID- 19118207
TI  - Integrin signalling at a glance.

PMID- 19118208
TI  - Linking integrin conformation to function.
AB  - Integrins are alphabeta heterodimeric adhesion receptors that relay signals
      bidirectionally across the plasma membrane between the extracellular matrix and
      cell-surface ligands, and cytoskeletal and signalling effectors. The physical and
      chemical signals that are controlled by integrins are essential for intercellular
      communication and underpin all aspects of metazoan existence. To mediate such
      diverse functions, integrins exhibit structural diversity, flexibility and
      dynamism. Conformational changes, as opposed to surface expression or clustering,
      are central to the regulation of receptor function. In recent years, there has
      been intense interest in determining the three-dimensional structure of
      integrins, and analysing the shape changes that underpin the interconversion
      between functional states. Considering the central importance of the integrin
      signalling nexus, it is perhaps no surprise that obtaining this information has
      been difficult, and the answers gained so far have been complicated. In this
      Commentary, we pose some of the key remaining questions that surround integrin
      structure-function relationships and review the evidence that supports the
      current models.

PMID- 19118209
TI  - Integrins and cell-fate determination.
AB  - All cellular processes are determined by adhesive interactions between cells and
      their local microenvironment. Integrins, which constitute one class of cell
      adhesion receptor, are multifunctional proteins that link cells to the
      extracellular matrix and organise integrin adhesion complexes at the cell
      periphery. Integrin-based adhesions provide anchor points for assembling and
      organising the cytoskeleton and cell shape, and for orchestrating migration.
      Integrins also control the fate and function of cells by influencing their
      proliferation, apoptosis and differentiation. Moreover, new literature
      demonstrates that integrins control the cell-division axis at mitosis. This
      extends the influence of integrins over cell-fate decisions, as daughter cells
      are frequently located in new microenvironments that determine their behaviour
      following cell division. In this Commentary, I describe how integrins influence
      cell-fate determination, placing particular emphasis on their role in influencing
      the direction of cell division and the orientation of the mitotic spindle.

PMID- 19118210
TI  - The mechanical integrin cycle.
AB  - Cells govern tissue shape by exerting highly regulated forces at sites of matrix
      adhesion. As the major force-bearing adhesion-receptor protein, integrins have a
      central role in how cells sense and respond to the mechanics of their
      surroundings. Recent studies have shown that a key aspect of mechanotransduction
      is the cycle by which integrins bind to the matrix at the leading cell edge,
      attach to the cytoskeleton, transduce mechanical force, aggregate in the plasma
      membrane as part of increasingly strengthened adhesion complexes, unbind and,
      ultimately, are recycled. This mechanical cycle enables the transition from early
      complexes to larger, more stable adhesions that can then rapidly release. Within
      this mechanical cycle, integrins themselves exhibit intramolecular conformational
      change that regulates their binding affinity and may also be dependent upon
      force. How the cell integrates these dynamic elements into a rigidity response is
      not clear. Here, we focus on the steps in the integrin mechanical cycle that are
      sensitive to force and closely linked to integrin function, such as the lateral
      alignment of integrin aggregates and related adhesion components.

PMID- 19118211
TI  - Mechanisms that regulate adaptor binding to beta-integrin cytoplasmic tails.
AB  - Cells recognize and respond to their extracellular environment through
      transmembrane receptors such as integrins, which physically connect the
      extracellular matrix to the cytoskeleton. Integrins provide the basis for the
      assembly of intracellular signaling platforms that link to the cytoskeleton and
      influence nearly every aspect of cell physiology; however, integrins possess no
      enzymatic or actin-binding activity of their own and thus rely on adaptor
      molecules, which bind to the short cytoplasmic tails of integrins, to mediate and
      regulate these functions. Many adaptors compete for relatively few binding sites
      on integrin tails, so regulatory mechanisms have evolved to reversibly control
      the spatial and temporal binding of specific adaptors. This Commentary discusses
      the adaptor proteins that bind directly to the tails of beta integrins and, using
      talin, tensin, filamin, 14-3-3 and integrin-linked kinase (ILK) as examples,
      describes the ways in which their binding is regulated.

PMID- 19118212
TI  - Integrins in cell migration--the actin connection.
AB  - The connection between integrins and actin is driving the field of cell migration
      in new directions. Integrins and actin are coupled through a physical linkage,
      which provides traction for migration. Recent studies show the importance of this
      linkage in regulating adhesion organization and development. Actin polymerization
      orchestrates adhesion assembly near the leading edge of a migrating cell, and the
      dynamic cross-linking of actin filaments promotes adhesion maturation. Breaking
      the linkage between actin and integrins leads to adhesion disassembly. Recent
      quantitative studies have revealed points of slippage in the linkage between
      actin and integrins, showing that it is not always efficient. Regulation of the
      assembly and organization of adhesions and their linkage to actin relies on
      signaling pathways that converge on components that control actin polymerization
      and organization.

PMID- 19118213
TI  - Integrins in mammary-stem-cell biology and breast-cancer progression--a role in
      cancer stem cells?
AB  - Cancer cells with stem cell-like properties (cancer stem cells) are believed to
      drive cancer and are associated with poor prognosis. Data from mouse models have
      demonstrated that integrins, the major cellular receptors for extracellular
      matrix components, have essential roles both during cancer initiation and
      progression, and during cell differentiation in normal development. By presenting
      an overview of the role of integrins in stem-cell biology and in cancer
      progression, this Commentary aims to present evidence for a role of integrins in
      the biology of cancer stem cells. Given the recent interest in the role of
      integrins in breast-cancer initiation and progression, we focus on the role of
      the members of the integrin family and their coupled signaling pathways in
      mammary-gland development and tumorigenesis.

PMID- 19118214
TI  - Integrins in immunity.
AB  - A successful immune response depends on the capacity of immune cells to travel
      from one location in the body to another--these cells are rapid migrators,
      travelling at speeds of microm/minute. Their ability to penetrate into tissues
      and to make contacts with other cells depends chiefly on the beta2 integrin known
      as LFA-1. For this reason, we describe the control of its activity in some
      detail. For the non-immunologist, the fine details of an immune response often
      seem difficult to fathom. However, the behaviour of immune cells, known as
      leukocytes (Box 1), is subject to the same biological rules as many other cell
      types, and this holds true particularly for the functioning of the integrins on
      these cells. In this Commentary, we highlight, from a cell-biology point of view,
      the integrin-mediated immune-cell migration and cell-cell interactions that occur
      during the course of an immune response.

PMID- 19118215
TI  - Mice that lack activity of alphavbeta6- and alphavbeta8-integrins reproduce the
      abnormalities of Tgfb1- and Tgfb3-null mice.
AB  - The arginine-glycine-aspartate (RGD)-binding integrins alphavbeta6 and
      alphavbeta8 activate latent TGFbeta1 and TGFbeta3 in vivo, but it is uncertain
      whether other RGD-binding integrins such as integrins alphavbeta5 and alphavbeta3
      activate these TGFbeta isoforms. To define the combined role of alphavbeta6- and
      alphavbeta8-integrin in TGFbeta activation, we analyzed mice lacking function of
      both integrins by means of gene deletion and/or pharmacologic inhibition. Most
      Itgb6-/-;Itgb8-/- embryos die at mid-gestation; those that survive develop cleft
      palate-as observed in Tgfb3-/- mice. Itgb8-/- mice treated with an anti
      alphavbeta6-integrin antibody develop severe autoimmunity and lack Langerhans
      cells-similar to Tgfb1-null mice. These results support a model in which TGFbeta3
      mediated palate fusion and TGFbeta1-mediated suppression of autoimmunity and
      generation of Langerhans cells require integrins alphavbeta6 and alphavbeta8 but
      not other RGD-binding integrins as TGFbeta activators.

PMID- 19118216
TI  - Integrins are required for the differentiation of visceral endoderm.
AB  - Integrins of the beta1 subfamily are highly expressed in the early mouse embryo
      and are essential for the formation of primitive germ layers from the inner cell
      mass (ICM). We investigated the mechanisms by which alphabeta1 integrins regulate
      ICM morphogenesis by using the embryonic-stem-cell-derived embryoid body (EB), a
      model for peri-implantation development. Ablation of integrin beta1 in EBs
      resulted in endoderm detachment and in maturation defects, which were manifested
      by the mislocalization of GATA4 in the cytoplasm and the markedly reduced
      synthesis of basement membrane (BM) components and the lineage marker disabled
      homolog 2. The mutant endoderm cells failed to spread on BM substrates, but could
      spread on vitronectin, which induced upregulation of alphavbeta3 integrin and
      integrin-dependent GATA4 nuclear translocation. Forced expression of integrin
      beta3 in the mutant EBs completely rescued endoderm morphogenesis, suggesting
      that integrin beta3 can substitute for integrin beta1 in the endoderm.
      Furthermore, the mitogen-activated protein kinases (MAPKs) ERK1 and ERK2 (ERK1/2)
      and p38 were activated in endoderm in an integrin-dependent fashion.
      Pharmacological inhibition of ERK1/2 or p38 MAPK blocked vitronectin-induced
      GATA4 nuclear translocation and endoderm maturation, whereas expression of a
      constitutively active ERK kinase (MEK1) or p38 MAPK in the mutant cells rescued
      endoderm maturation in integrin-beta1-null endoderm cells. Collectively, these
      results suggest that integrins are required for both the stable adhesion and
      maturation of visceral endoderm, the latter being mediated through the activation
      of ERK1/2 and p38 MAPK.

PMID- 19118217
TI  - EphA1 interacts with integrin-linked kinase and regulates cell morphology and
      motility.
AB  - The Eph-ephrin receptor-ligand system is implicated in cell behavior and
      morphology. EphA1 is the founding member of the Eph receptors, but little is
      known about its function. Here, we show that activation of EphA1 kinase inhibits
      cell spreading and migration in a RhoA-ROCK-dependent manner. We also describe a
      novel interaction between EphA1 and integrin-linked kinase (ILK), a mediator of
      interactions between integrin and the actin cytoskeleton. The C-terminal sterile
      alpha motif (SAM) domain of EphA1 is required and the ankyrin region of ILK is
      sufficient for the interaction between EphA1 and ILK. The interaction is
      independent of EphA1 kinase activity but dependent on stimulation of the EphA1
      ligand ephrin-A1. Activation of EphA1 kinase resulted in a decrease of ILK
      activity. Finally, we demonstrated that expression of a kinase-active form of ILK
      (S343D) rescued the EphA1-mediated spreading defect, and attenuated RhoA
      activation. These results suggest that EphA1 regulates cell morphology and
      motility through the ILK-RhoA-ROCK pathway.

PMID- 19118218
TI  - Integrin-linked kinase is required for vitronectin-mediated internalization of
      Streptococcus pneumoniae by host cells.
AB  - By interacting with components of the human host, including extracellular matrix
      (ECM) proteins, Streptococcus pneumoniae has evolved various strategies for
      colonization. Here, we characterized the interaction of pneumococci with the
      adhesive glycoprotein vitronectin and the contribution of this protein to
      pneumococcal uptake by host cells in an integrin-dependent manner. Specific
      interaction of S. pneumoniae with the heparin-binding sites of purified
      multimeric vitronectin was demonstrated by flow cytometry analysis. Host-cell
      bound vitronectin promoted pneumococcal adherence to and invasion into human
      epithelial and endothelial cells. Pneumococci were trapped by microspike-like
      structures, which were induced upon contact of pneumococci with host-cell-bound
      vitronectin. Alphavbeta3 integrin was identified as the major cellular receptor
      for vitronectin-mediated adherence and uptake of pneumococci. Ingestion of
      pneumococci by host cells via vitronectin required a dynamic actin cytoskeleton
      and was dependent on integrin-linked kinase (ILK), phosphatidylinositol 3-kinase
      (PI3K), and protein kinase B (Akt), as demonstrated by gene silencing or in
      inhibition experiments. In conclusion, pneumococci exploit the vitronectin
      alphavbeta3-integrin complex as a cellular receptor for invasion and this
      integrin-mediated internalization requires the cooperation between the host
      signalling molecules ILK, PI3K and Akt.

PMID- 19118219
TI  - JAM-A promotes neutrophil chemotaxis by controlling integrin internalization and
      recycling.
AB  - The membrane-associated adhesion molecule JAM-A is required for neutrophil
      infiltration in inflammatory or ischemic tissues. JAM-A expressed in both
      endothelial cells and neutrophils has such a role, but the mechanism of action
      remains elusive. Here we show that JAM-A has a cell-autonomous role in neutrophil
      chemotaxis both in vivo and in vitro, which is independent of the interaction of
      neutrophils with endothelial cells. On activated neutrophils, JAM-A concentrates
      in a polarized fashion at the leading edge and uropod. Surprisingly, a
      significant amount of this protein is internalized in intracellular endosomal
      like vesicles where it codistributes with integrin beta1. Clustering of beta1
      integrin leads to JAM-A co-clustering, whereas clustering of JAM-A does not
      induce integrin association. Neutrophils derived from JAM-A-null mice are unable
      to correctly internalize beta1 integrins upon chemotactic stimuli and this causes
      impaired uropod retraction and cell motility. Consistently, inhibition of
      integrin internalization upon treatment with BAPTA-AM induces a comparable
      phenotype. These data indicate that JAM-A is required for the correct
      internalization and recycling of integrins during cell migration and might
      explain why, in its absence, the directional migration of neutrophils towards an
      inflammatory stimulus is markedly impaired.

PMID- 19118220
TI  - Integrin alpha3beta1 inhibits directional migration and wound re
      epithelialization in the skin.
AB  - Re-epithelialization after skin wounding requires both migration and
      hyperproliferation of keratinocytes. Laminin-332 is deposited during migration
      over the provisional matrix. To investigate the function of the laminin-332
      binding integrin alpha3beta1 in wound re-epithelialization, we generated
      Itga3flox/flox; K14-Cre mice lacking the alpha3 subunit specifically in the basal
      layer of the epidermis. These mice are viable but display several skin defects,
      including local inflammation, hair loss, basement membrane duplication and
      microblistering at the dermal-epidermal junction, whereas hemidesmosome assembly
      and keratinocyte differentiation are not impaired. Wound healing is slightly
      faster in the absence of integrin alpha3beta1, whereas proliferation, the
      distribution of other integrins and the deposition of basement membrane proteins
      in the wound bed are unaltered. In vitro, cell spreading is rescued by increased
      surface expression of alpha6beta1 integrin in the absence of integrin alpha3. The
      alpha3-deficient keratinocytes migrate with an increased velocity and
      persistence, whereas proliferation, growth factor signaling, hemidesmosome
      assembly, and laminin-332 deposition appeared to be normal. We suggest that
      integrin alpha3beta1 delays keratinocyte migration during wound re
      epithelialization, by binding to the laminin-332 that is newly deposited on the
      wound bed.

PMID- 19118223
TI  - Pulmonary infiltrates in patients with malignancies: why and how neutropenia
      influences clinical reasoning.

PMID- 19118221
TI  - Binding of laminin-1 to monosialoganglioside GM1 in lipid rafts is crucial for
      neurite outgrowth.
AB  - Laminin-1, an extracellular matrix molecule, promotes neurite outgrowth through
      the interaction of integrin and actin. Monosialoganglioside GM1 in the lipid
      rafts associates with and activates the NGF receptor TrkA, and enhances neurite
      outgrowth. However, the role of GM1 in laminin-1-induced neurite outgrowth was
      still unclear. Here, we describe that laminin-1 binds to GM1 through a
      carbohydrate moiety and a specific conformation of GM1, induces focal formation
      of large clusters of GM1, and enhances the relocation of TrkA in the membrane of
      dorsal root ganglion (DRG) and PC12 cells. We found that laminin-1-mediated
      clustering of GM1 causes the translocation and enrichment of beta1 integrin in
      lipid rafts--where TrkA colocalizes with beta1 integrin--and the activation of
      Lyn, Akt and MAPK to promote the outgrowth of neurites. Our results suggest that
      the binding of laminin-1 to GM1 facilitates the formation of a focal microdomain
      in the membrane, and enhances signal transduction that promotes neurite outgrowth
      by linking NGF-TrkA signaling with the laminin-integrin signaling pathways.

PMID- 19118222
TI  - Safety of long-acting beta-agonists: urgent need to clear the air remains.

PMID- 19118224
TI  - Asthma therapy: how far have we come, why did we fail and where should we go
      next?
AB  - Reversible airflow obstruction and nonspecific airway hyperresponsiveness are: 1)
      the two key features of asthma; 2) the primary concern for asthma patients; and
      3) both directly caused by the airway smooth muscle (ASM). As such, controlling
      bronchoconstriction should be of primary importance. Unfortunately, all existing
      pharmacological asthma therapies that specifically target the ASM are based on
      decades old strategies. In the present study, the evolution of pharmacological
      asthma therapy will be briefly discussed, some explanations will be suggested as
      to why substantial new advances in this area have not occurred in several years
      and, finally, several new directions for novel asthma therapies will be proposed.

PMID- 19118225
TI  - Macrophages within NSCLC tumour islets are predominantly of a cytotoxic M1
      phenotype associated with extended survival.
AB  - There is a marked survival advantage for patients with nonsmall cell lung cancer
      (NSCLC) expressing high numbers of macrophages in their tumour islets. The
      primary aim of the present study was to determine the immunological phenotype of
      NSCLC-associated macrophages. CD68(+) macrophages expressing markers of a
      cytotoxic M1 phenotype or a noncytotoxic M2 phenotype were identified in the
      islets and stroma of surgically resected tumours from 20 patients with extended
      survival (median 92.7 months) and 20 with poor survival (median 7.7 months),
      using immunohistochemistry. The islet density of both M1 and M2 macrophages was
      markedly increased in extended compared with poor survival patients. In the
      extended survival group, M1 islet density was significantly increased compared
      with M2 density, 70% of islet macrophages were positive for M1 markers versus 38%
      for M2, and the islet:stromal ratio of M1 macrophages was markedly increased
      compared with M2. The 5-yr survival for patients with above and below median
      expression of M1 macrophages in the islets was >75 and <5%, respectively.
      Macrophages infiltrating the tumour islets in nonsmall cell lung cancer were
      predominantly of the M1 phenotype in patients with extended survival. The
      survival advantage conferred by islet macrophage infiltration may be related to
      their cytotoxic antitumour activity.

PMID- 19118226
TI  - Long-term relapses after 12-month treatment for Mycobacterium kansasii lung
      disease.
AB  - Long-lasting therapy for Mycobacterium kansasii lung disease with rifampin
      containing multidrug regimens is needed to avoid relapses. The aim of the present
      study is to evaluate a short multidrug treatment regimen for M. kansasii lung
      disease. A retrospective observational study of 75 patients with M. kansasii lung
      disease was conducted in a teaching hospital from January 1990 to December 2005.
      In total, 75 (67.6%) out of 111 patients diagnosed with M. kansasii lung disease
      completed a 12-month multidrug treatment regimen, including rifampin, isoniazid
      and ethambutol, supplemented with streptomycin during the first 2-3 months. After
      a 41.5-month median follow-up, five (6.6%) patients relapsed. The relapse rate
      was 2.19 (95% confidence interval 0.71-5.12) per 100 person.yrs. Treatment
      compliance was considered to be appropriate in all five patients and no drug
      resistance developed in any case. In conclusion, a 12-month fixed-course
      treatment is effective in most cases of Mycobacterium kansasii lung disease, but
      may not be long enough for all patients.

PMID- 19118227
TI  - Reversing the tuberculosis upwards trend: a success story in Romania.
AB  - At present, no published evidence is available on the effectiveness of the DOTS
      (directly observed treatment, short-course) strategy in reducing the incidence of
      tuberculosis (TB) within a country in the European "hot spots". The present study
      aimed to demonstrate the effectiveness of the strategy implementation in
      reversing the epidemiological TB trend in Romania based on programmatic data
      analysis. Key programme indicators were analysed from 1998 to 2007, and included
      DOTS coverage, case-detection rate, treatment success and overall incidence of
      notified cases. Internationally agreed definitions were used. The key programme
      indicators began declining and the World Health Assembly targets were reached
      (79% case-detection of new sputum-smear positive cases and 85.5% success rate in
      new culture-positive TB cases), 7 yrs after initiation of the DOTS expansion. The
      success story in Romania suggests that other middle-income, high-incidence
      countries (i.e. those belonging to the former Soviet Union) might be able to
      reach the World Health Assembly Targets and curb the burden of tuberculosis.

PMID- 19118228
TI  - Long-term macrolide therapy in chronic inflammatory airway diseases.
AB  - In addition to direct antibacterial actions, 14- and 15-member-ring macrolides
      have immune modulating effects that appear to be the reason for clinical benefit
      in diffuse panbronchiolitis. A literature search was conducted for studies of the
      clinical effectiveness of macrolides in other chronic lung conditions. A number
      of studies were identified that showed short-term beneficial outcomes or the
      potential for such outcomes in cystic fibrosis, bronchiectasis, chronic
      obstructive pulmonary disease, asthma and post-transplant obliterative
      bronchiolitis. The studies were limited by small patient numbers, different
      outcome measures and short-term follow-up, and were not designed to assess
      potentially harmful effects. Further large prospective and long-term studies are
      required in order to identify potential benefit and harm before these agents can
      be recommended routinely for these conditions.

PMID- 19118229
TI  - Animal models of ventilator-associated pneumonia.
AB  - Animal models are an essential step between "in vitro" testing and clinical
      studies. Different animal models have been useful for the study of
      pathophysiology, diagnosis and therapy in ventilator-associated pneumonia (VAP).
      Aspiration has been studied in dog and cat models and bacteriological diagnosis
      has been evaluated in baboons. Pigs have been used for studying either
      spontaneous or induced VAP. Intubated piglets in prone position were administered
      analgesia and muscle paralysis was induced, and the intubated piglets underwent
      mechanical ventilation for several days. In this model, spontaneous VAP due to
      common bacterial pig colonisation develops within a few days. Pneumonia can also
      be induced by inoculating high concentrations of microorganisms (Pseudomonas
      aeruginosa and methicillin-resistant Staphylococcus aureus). Different clinical,
      physiological, microbiological and pathological parameters of infection have been
      studied in this model. In addition, administration of antibiotics and
      inflammatory modulators and their consequences in microbiological eradication and
      local and systemic inflammation have been evaluated with interesting
      translational results. Although bronchial inoculation of healthy subjects does
      not resemble the common pathophysiological mechanisms, the experimental model of
      ventilator-associated pneumonia induced by the inoculation of high concentrations
      of microorganisms in mechanically ventilated piglets is useful for the study of
      the local and systemic responses of lung infection and for the determination of
      potential measures of prevention or therapeutic modulation.

PMID- 19118230
TI  - Pulmonary veno-occlusive disease.
AB  - Pulmonary veno-occlusive disease (PVOD) is currently classified as a subgroup of
      pulmonary arterial hypertension (PAH) and accounts for 5-10% of cases initially
      considered to be idiopathic PAH. PVOD has been described as idiopathic or
      complicating other conditions, including connective tissue diseases, HIV
      infection, bone marrow transplantation, sarcoidosis and pulmonary Langerhans cell
      granulomatosis. PVOD shares broadly similar clinical presentation, genetic
      background and haemodynamic characteristics with PAH. Compared to PAH, PVOD is
      characterised by a higher male/female ratio, higher tobacco exposure, lower
      arterial oxygen tension at rest, lower diffusing capacity of the lung for carbon
      monoxide, and lower oxygen saturation nadir during the 6-min walk test. High
      resolution computed tomography (HRCT) of the chest can be suggestive of PVOD in
      the presence of centrilobular ground-glass opacities, septal lines and lymph node
      enlargement. Similarly, occult alveolar haemorrhage is associated with PVOD. A
      noninvasive diagnostic approach using HRCT of the chest, arterial blood gases,
      pulmonary function tests and bronchoalveolar lavage could be helpful for the
      detection of PVOD patients and in avoiding high-risk surgical lung biopsy for
      histological confirmation. PVOD is characterised by a poor prognosis and the
      possibility of developing severe pulmonary oedema with specific PAH therapy. Lung
      transplantation is the treatment of choice. Cautious use of specific PAH therapy
      can, however, be helpful in some patients.

PMID- 19118231
TI  - Integrated PET/CT in the staging of nonsmall cell lung cancer: technical aspects
      and clinical integration.
AB  - Lung cancer is a common disease and is a leading cause of death in many
      countries. The management of lung cancer is directed by an optimal staging of the
      tumour. Integrated positron emission tomography (PET)/computed tomography (CT) is
      an anatomo-metabolic imaging modality that has recently been introduced to
      clinical practice and combines two different techniques: CT, which provides very
      detailed anatomic information; and PET, which provides metabolic information. One
      of the advantages of PET/CT is the improved image interpretation. This
      improvement can result in the detection of lesions initially not seen on CT or
      PET, a more precise location of lesions, a better characterisation of the lesion
      as benign or malignant and a better differentiation between tumour and
      surrounding structures. Initial studies demonstrate better results for PET/CT in
      the staging of lung cancer in comparison with PET alone, CT alone or visual
      correlation of PET and CT. The purpose of the present article is to discuss
      technical aspects of integrated PET/CT and to attempt to outline how to introduce
      integrated PET/CT in clinical and daily practice.

PMID- 19118232
TI  - Pulmonary veno-occlusive disease in myeloproliferative disorder.
AB  - The present study reports a case of biopsy-proven pulmonary veno-occlusive
      disease as a cause of severe pulmonary hypertension in a patient suffering from a
      chronic myeloproliferative disorder. The pulmonary disease evolved favourably
      under treatment with defibrotide, a pro-fibrinolytic medication used in hepatic
      veno-occlusive disease.

PMID- 19118233
TI  - Animal models of airway hyperresponsiveness.

PMID- 19118234
TI  - Re: Are asymptomatic airway hyperresponsiveness and allergy risk factors for
      asthma? A longitudinal study.

PMID- 19118235
TI  - Anti-elastin autoantibodies are not present in combined pulmonary fibrosis and
      emphysema.

PMID- 19118236
TI  - Pre-immigration screening for pulmonary tuberculosis: the unanswered questions.

PMID- 19118238
TI  - The art of primary prevention and risk assessment: homocysteine revisited.

PMID- 19118239
TI  - Understanding stroke in women: similar care, worse outcomes?

PMID- 19118240
TI  - Lack of impact of paramedic training and use of the cincinnati prehospital stroke
      scale on stroke patient identification and on-scene time.
AB  - BACKGROUND AND PURPOSE: The Cincinnati Prehospital Stroke Scale (CPSS) is
      recommended for emergency medical services use in identifying patients with
      stroke. Data evaluating its performance in the field are limited. We assessed the
      impact of training and use of the CPSS on the accuracy of paramedics' stroke
      patient identification and on-scene time. METHODS: A 1-hour interactive
      educational presentation on the use of the CPSS was conducted for paramedics
      transporting patients to an academic medical center. Patients with
      stroke/transient ischemic attack (TIA) were identified retrospectively from
      paramedic records and were compared with the hospital's prospective stroke
      registry for the year before and after the training. RESULTS: There were 154
      patients with suspected stroke/transient ischemic attack identified (56% women,
      53% white, 44% black, mean age 67+/-16 years). There was no difference in
      paramedics' use of the CPSS (37.5% versus 23.8%, P=0.123) or accuracy of
      stroke/TIA patient identification (40.5% versus 38.9%, P=0.859) before and after
      training. Of responsive patients identified by paramedics as having a stroke/TIA,
      57% had an abnormality in at least one CPSS item with no effect on on-scene time
      (17+/-6 minutes with a normal versus 18+/-6 minutes with an abnormal CPSS,
      P=0.492). Those with a final diagnosis of stroke/TIA (n=61, 40%) more frequently
      had at least one abnormal CPSS item (70% versus 30%, P=0.008, sensitivity 0.71,
      specificity 0.52) with 49% of patients with an abnormality having a discharge
      diagnosis of stroke/TIA. CONCLUSIONS: Paramedic training in the CPSS, or its use,
      had no impact on the accuracy of their identification of patients with stroke/TIA
      or on-scene time.

PMID- 19118241
TI  - Interhemispheric distribution of Alzheimer disease and vascular pathology in
      brain aging.
AB  - BACKGROUND AND PURPOSE: Most of the neuropathological studies in brain aging were
      based on the assumption of a symmetrical right-left hemisphere distribution of
      both Alzheimer disease and vascular pathology. To explore the impact of
      asymmetrical lesion formation on cognition, we performed a clinicopathological
      analysis of 153 cases with mixed pathology except macroinfarcts. METHODS:
      Cognitive status was assessed prospectively using the Clinical Dementia Rating
      scale; neuropathological evaluation included assessment of Braak neurofibrillary
      tangle and Ass deposition staging, microvascular pathology, and lacunes. The
      right-left hemisphere differences in neuropathological scores were evaluated
      using the Wilcoxon signed rank test. The relationship between the
      interhemispheric distribution of lesions and Clinical Dementia Rating scores was
      assessed using ordered logistic regression. RESULTS: Unlike Braak neurofibrillary
      tangle and Ass deposition staging, vascular scores were significantly higher in
      the left hemisphere for all Clinical Dementia Rating scores. A negative
      relationship was found between Braak neurofibrillary tangle, but not Ass staging,
      and vascular scores in cases with moderate to severe dementia. In both
      hemispheres, Braak neurofibrillary tangle staging was the main determinant of
      cognitive decline followed by vascular scores and Ass deposition staging. The
      concomitant predominance of Alzheimer disease and vascular pathology in the right
      hemisphere was associated with significantly higher Clinical Dementia Rating
      scores. CONCLUSIONS: Our data show that the cognitive impact of Alzheimer disease
      and vascular lesions in mixed cases may be assessed unilaterally without major
      information loss. However, interhemispheric differences and, in particular,
      increased vascular and Alzheimer disease burden in the right hemisphere may
      increase the risk for dementia in this group.

PMID- 19118242
TI  - Thrombolysis in childhood stroke: report of 2 cases and review of the literature.
AB  - BACKGROUND AND PURPOSE: No controlled, randomized trial has investigated whether
      intravenous, intra-arterial (IAT), or mechanical thrombolysis is beneficial in
      children with ischemic stroke. We report 2 children who underwent IAT for acute
      ischemic stroke and include them in a review about intravenous thrombolysis, IAT,
      and mechanical thrombolysis for childhood stroke. METHODS: We searched in MEDLINE
      and EMBASE for studies that reported on treatment of childhood stroke with
      intravenous thrombolysis, IAT, or mechanical thrombolysis in the presence of
      occlusion of the basilar artery, sphenoidal, or insular middle cerebral artery.
      To be included in this review, the following findings had to be reported: (1)
      stroke severity at presentation; (2) cerebral imaging findings before
      thrombolysis; (3) time to treatment; (4) dose of the thrombolytic agent; (5) pre-
      and postinterventional angiographic findings in IAT; and (6) outcome assessed at
      hospital discharge or within 12 months after thrombolysis. RESULTS: Adequate data
      were available in 17 children (including our 2 own cases) who underwent
      intravenous thrombolysis (n=6), IAT (n=10), or mechanical thrombolysis (n=1). No
      symptomatic intracranial hemorrhage occurred, but 2 asymptomatic intracranial
      hemorrhages were present. Sixteen children (94%) survived, and 12 (71%) had a
      good outcome (modified Rankin Scale score 0 or 1). CONCLUSIONS: The available
      data about thrombolysis in pediatric stroke are limited. They suggest that this
      treatment may be beneficial in children with ischemic stroke. Controlled,
      randomized trials are needed to determine whether thrombolysis is useful in
      childhood stroke.

PMID- 19118244
TI  - Involvement of PTEN promoter methylation in cerebral cavernous malformations.
AB  - BACKGROUND AND PURPOSE: Cerebral cavernous malformations (CCMs) are prevalent
      cerebral vascular lesions involving aberrant angiogenesis. However, the
      underlying mechanism is poorly understood. Phosphatase and tension homolog
      deleted on chromosome 10 (PTEN), a tumor suppressor, is frequently deficient in
      various pathologies due to mutation or epigenetic alterations. PTEN promoter
      hypermethylation is a major epigenetic silencing mechanism leading to activation
      of angiogenesis in tumors. The present study aimed to investigate whether PTEN
      promoter methylation was involved in CCMs. METHODS: PTEN promoter methylation was
      detected in surgical specimens of CCMs (n=69) by methylation-specific polymerase
      chain reaction. The methylation status was correlated to the clinical
      manifestations and to PTEN expression, which was analyzed by both Western blot
      and immunohistochemistry. To investigate the endothelial proliferation and the
      potential signaling pathways affected by PTEN methylation, proliferating cell
      nuclear antigen as well as phosphor-Akt and phosphor-Erk1,2 were detected by
      immunofluorescence and Western blot, respectively, in CCM specimens. RESULTS:
      Methylation-specific polymerase chain reaction revealed PTEN promoter methylation
      in 15.9% CCMs. Strikingly, 5 of 6 familial CCMs showed PTEN promoter methylation
      (83.3%), which was significantly higher than in sporadic cases (9.4%; P<0.001).
      In addition, PTEN promoter methylation appeared more frequently in multiple CCMs,
      including familial cases (46.7%), than that in single-lesioned CCMs (11.8%;
      P<0.05). Immunostaining and Western blot revealed a more significant PTEN
      downregulation in PTEN-methylated CCMs in comparison to PTEN-unmethylated CCMs.
      Reduced PTEN expression was inversely correlated to the expression of
      proliferating cell nuclear antigen and to the activation of Erk1,2, but not of
      Akt. CONCLUSIONS: We reported here for the first time the involvement of PTEN
      promoter methylation in CCMs, particularly in familial CCMs, suggesting this
      epigenetic alteration as a potential pathomechanism of CCMs. The identification
      of Erk1,2 as triggered signaling in the lesions may be valuable for the
      development of effective therapy for this disease.

PMID- 19118245
TI  - Impaired baroreceptor reflex sensitivity in acute stroke is associated with
      insular involvement, but not with carotid atherosclerosis.
AB  - BACKGROUND AND PURPOSE: Impaired baroreflex sensitivity (BRS) has been previously
      shown to be of prognostic value in patients with cardiovascular disease and
      stroke. Because baroreflex seems to be blunted by both carotid atherosclerosis
      and by lesions affecting central processing, controversy exists regarding the
      etiology of stroke-related baroreflex changes. The insula may play a central role
      in baroreflex modulation. The aim of the study was therefore to examine BRS in
      patients with acute stroke with regard to carotid atherosclerosis and insular
      involvement. METHODS: We evaluated spontaneous BRS in 96 patients with acute
      stroke within 72 hours of ictus and 41 control subjects using a sequential
      crosscorrelation method. RESULTS: Fifty-two patients with ischemic stroke and 44
      patients with intracerebral hemorrhage, mean age 58.4 years, were included. With
      comparable carotid atherosclerosis profiles, patients with stroke had
      significantly lower BRS than control subjects (3.3 versus 5.3, P<0.001). Carotid
      atherosclerosis had no influence on variance of the BRS values in the acute
      stroke group. Patients with insular involvement had significantly lower BRS than
      patients with no insular involvement (2.55 versus 4.35, P=0.001) or control
      subjects (2.55 versus 5.3, P<0.001). Furthermore, patients with left insular
      involvement had significantly lower BRS than patients with right insular
      involvement (2.3 versus 3.5, P=0.049). There was no significant difference
      between patients with no insular lesions and control subjects (P=0.263).
      CONCLUSIONS: We demonstrated that baroreflex impairment in acute stroke is not
      associated with carotid atherosclerosis but with insular involvement. Both
      insulae seem to participate in processing the baroreceptor information with the
      left insula being more dominant.

PMID- 19118243
TI  - High-dose B vitamin supplementation and progression of subclinical
      atherosclerosis: a randomized controlled trial.
AB  - BACKGROUND AND PURPOSE: Although plasma total homocysteine (tHcy) levels are
      associated with cardiovascular disease, it remains unclear whether homocysteine
      is a cause or a marker of atherosclerotic vascular disease. We determined whether
      reduction of tHcy levels with B vitamin supplementation reduces subclinical
      atherosclerosis progression. METHODS: In this double-blind clinical trial, 506
      participants 40 to 89 years of age with an initial tHcy >8.5 micromol/L without
      diabetes and cardiovascular disease were randomized to high-dose B vitamin
      supplementation (5 mg folic acid+0.4 mg vitamin B(12)+50 mg vitamin B(6)) or
      matching placebo for 3.1 years. Subclinical atherosclerosis progression across 3
      vascular beds was assessed using high-resolution B-mode ultrasonography to
      measure carotid artery intima media thickness (primary outcome) and multidetector
      spiral CT to measure aortic and coronary artery calcium (secondary outcome).
      RESULTS: Although the overall carotid artery intima media thickness progression
      rate was lower with B vitamin supplementation than with placebo, statistically
      significant between-group differences were not found (P=0.31). However, among
      subjects with baseline tHcy >or=9.1 micromol/L, those randomized to B vitamin
      supplementation had a statistically significant lower average rate of carotid
      artery intima media thickness progression compared with placebo (P=0.02); among
      subjects with a baseline tHcy <9.1 micromol/L, there was no significant treatment
      effect (probability value for treatment interaction=0.02). B vitamin
      supplementation had no effect on progression of aortic or coronary artery
      calcification overall or within subgroups. CONCLUSIONS: High-dose B vitamin
      supplementation significantly reduces progression of early-stage subclinical
      atherosclerosis (carotid artery intima media thickness) in well-nourished healthy
      B vitamin "replete" individuals at low risk for cardiovascular disease with a
      fasting tHcy >or=9.1 micromol/L.

PMID- 19118246
TI  - Sex differences in stroke care and outcome in the Swedish national quality
      register for stroke care.
AB  - BACKGROUND AND PURPOSE: Previous reports concerning sex-related differences in
      stroke management and outcome are inconsistent and are sometimes difficult to
      interpret. We used data from a national stroke register to further explore
      possible differences between men and women in baseline characteristics, stroke
      treatment, and outcome. METHODS: This study included 24633 stroke events
      registered in Riks-Stroke, the Swedish national quality register for stroke care,
      during 2006. Information on background variables and treatment was collected
      during the hospital stay. After 3 months, the patients' living situation and
      outcome were assessed. RESULTS: Women were older than men when they had their
      stroke (mean age, 78.4 versus 73.6 years; P<0.001). On admission to the hospital,
      women were more often unconscious. Among conscious patients, there was no sex
      related difference in the use of stroke unit care. Men and women had equal
      probability to receive thrombolysis and oral anticoagulants. Women were more
      likely to develop deep venous thromboses and fractures, whereas men were more
      likely to develop pneumonia during their hospital stay. Women had a lower 3-month
      survival, a difference that was associated with higher age and impaired level of
      consciousness on admission. Women were less often living at home at the 3-month
      follow-up. However, the difference in residency was not present in patients <85
      years who were living at home without community support before the stroke.
      CONCLUSIONS: Reported sex differences in stroke care and outcome were mainly
      explained by the women's higher age and lower level of consciousness on
      admission.

PMID- 19118247
TI  - Autopsy prevalence of proximal extracranial atherosclerosis in patients with
      fatal stroke.
AB  - BACKGROUND AND PURPOSE: Extracranial atherosclerosis, proximal to the carotid
      bifurcation and V3 segment of the vertebral artery, is considered to be an
      infrequent condition with a benign prognosis. However, its prevalence may be
      underestimated due to lack of data. We aimed to determine the prevalence of
      proximal extracranial plaques and stenosis in the common carotid artery,
      innominate and subclavian arteries, and proximal vertebral artery. METHODS: We
      performed a systematic analysis of intra- and extracranial arteries, the aortic
      arch, and the heart in 339 consecutive autopsies of patients with stroke; 259
      patients had brain infarction; 80 patients had brain hemorrhage and were used as
      control subjects. Clinical history, risk factors, imaging data, and general
      autopsy reports were analyzed. RESULTS: Proximal extracranial plaques and
      stenosis were present in the arteries of 46.9% and 19.8% of patients,
      respectively, without a significant difference between brain infarction and brain
      hemorrhage groups. Proximal extracranial atherosclerosis occurred more frequently
      in the proximal vertebral artery than in other arteries (stenosis prevalence
      12.7% versus 5.3% in the common carotid artery) and in patients with posterior
      circulation brain infarction (except for the posterior cerebral artery
      territory). More specifically, atherosclerosis in the proximal vertebral artery
      was significantly associated with posterior circulation brain infarction (age-
      and sex-adjusted OR, 2.31; 95% CI, 1.28 to 4.17 for plaques and 2.10; 95% CI,
      1.01 to 4.38 for stenosis) using patients with isolated anterior circulation
      infarctions as control subjects. CONCLUSIONS: Proximal extracranial
      atherosclerosis was frequent and was significantly associated with brainstem
      infarcts. These findings support the importance of a systematic workup, including
      the evaluation of proximal extracranial atherosclerotic lesions.

PMID- 19118248
TI  - Isolated lateral sinus thrombosis: a series of 62 patients.
AB  - BACKGROUND AND PURPOSE: Isolated lateral sinus thrombosis was long considered a
      complication of middle ear disease. Little attention has been recently paid to
      this variety of thrombosis. We therefore reviewed all cases of isolated lateral
      sinus thrombosis prospectively collected in our center (1997 to 2006). METHODS:
      Among 195 patients with cerebral venous thrombosis (CVT), we identified 157
      patients with lateral sinus thrombosis, including 62 patients with isolated
      lateral sinus thrombosis. Clinical, etiologic, and prognostic features were
      compared with those of other 133 CVT cases. RESULT: Sixty-two patients (32%) had
      isolated lateral sinus thrombosis. Headaches were present in 95% of patients. The
      main clinical presentation was isolated headache in 28 patients (45%), whereas 15
      (24%) had isolated intracranial hypertension. Nineteen patients (31%) had at
      least one focal sign (deficit and/or focal seizure). Dysphasia was the most
      common one (8 patients). Compared with the other 133 CVT cases, presentation with
      isolated headaches was the most frequent one (P<0.001). Parenchymal lesions were
      found in 19 cases and were less frequent than in other CVT cases (P=0.007).
      Numerous causes or predisposing factors were identified without a difference in
      repartition with other patients with CVT, particularly for local or infectious
      causes. Treatment consisted of anticoagulation in all patients. Clinical outcome
      was good with complete recovery in 57 patients (92%). One patient died after the
      occurrence of massive pulmonary emboli despite adequate anticoagulation. Three
      patients had sequelae (no difference with the other CVT). CONCLUSIONS: Isolated
      lateral sinus thrombosis is a frequent variety of CVT, accounting for one third
      of all CVT. It presents in more than two thirds of cases with headache as the
      only symptom either isolated or less frequently associated with papilledema. This
      stresses the need for CVT workup in a patient with a recent unexplained headache.

PMID- 19118249
TI  - Cardiovascular death and nonfatal myocardial infarction in acute coronary
      syndrome patients receiving coronary stenting are predicted by residual platelet
      reactivity to ADP detected by a point-of-care assay: a 12-month follow-up.
AB  - BACKGROUND: The clinical impact of platelet aggregation assessed by point-of-care
      assays is unknown. We sought to evaluate whether high residual platelet
      reactivity (RPR) to ADP during clopidogrel therapy, measured by a point-of-care
      assay, predicts adverse clinical events in acute coronary syndrome patients
      undergoing percutaneous coronary intervention. METHODS AND RESULTS: We used the
      VerifyNow P2Y12 assay (Accumetrics Inc, San Diego, Calif) to determine RPR to ADP
      in 683 patients with acute coronary syndrome undergoing dual-antiplatelet therapy
      who underwent percutaneous coronary intervention with bare-metal or drug-eluting
      stent implantation. All patients received a single 600-mg clopidogrel loading
      dose followed by 75 mg of clopidogrel daily and 100 to 325 mg of aspirin daily.
      The end points of the study at follow-up of 12 months were cardiovascular death,
      nonfatal myocardial infarction (MI), and target-vessel revascularization. At a 12
      month follow-up, we found 51 ischemic events (24 cardiovascular deaths [3.5%], 27
      nonfatal MIs [3.9%]) and 40 target-vessel revascularizations (5.8%). By receiver
      operating characteristic curve (ROC) analysis, the optimal cutoff value in
      predicting 12-month cardiovascular death and nonfatal MI was P2Y12 reaction unit
      values > or =240. RPR, defined in the presence of P2Y12 reaction unit values
      above this cutoff, was found to be a significant and independent predictor of
      cardiovascular death and nonfatal MI in a model that adjusted for cardiovascular
      risk factors, renal failure, reduced left ventricular ejection fraction,
      multivessel disease, total stent length, bifurcation lesions, number of lesions
      treated, type of stent, and use of glycoprotein IIb/IIIa inhibitors
      (cardiovascular death: hazard ratio 2.55, 95% CI 1.08 to 6.07, P=0.034; nonfatal
      MI: hazard ratio 3.36, 95% CI 1.49 to 7.58, P=0.004). No significant association
      was found between high RPR and the risk of target-vessel revascularization.
      CONCLUSIONS: RPR to ADP with clopidogrel therapy, measured by the point-of-care
      assay VerifyNow P2Y12, is able to detect acute coronary syndrome patients at risk
      of 12-month cardiovascular death and nonfatal MI. The optimal cutoff value was
      identified as being 240 P2Y12 reaction units.

PMID- 19118250
TI  - Disruption of striated preferentially expressed gene locus leads to dilated
      cardiomyopathy in mice.
AB  - BACKGROUND: The striated preferentially expressed gene (Speg) generates 4
      different isoforms through alternative promoter use and tissue-specific splicing.
      Depending on the cell type, Speg isoforms may serve as markers of striated or
      smooth muscle differentiation. METHODS AND RESULTS: To elucidate function of Speg
      gene isoforms, we disrupted the Speg gene locus in mice by replacing common exons
      8, 9, and 10 with a lacZ gene. beta-Galactosidase activity was detected in
      cardiomyocytes of the developing heart starting at day 11.5 days post coitum
      (dpc). beta-Galactosidase activity in other cell types, including vascular smooth
      muscle cells, did not begin until 18.5 dpc. In the developing heart, protein
      expression of only Spegalpha and Spegbeta isoforms was present in cardiomyocytes.
      Homozygous Speg mutant hearts began to enlarge by 16.5 dpc, and by 18.5 dpc, they
      demonstrated dilation of right and left atria and ventricles. These cardiac
      abnormalities in the absence of Speg were associated with a cellular hypertrophic
      response, myofibril degeneration, and a marked decrease in cardiac function.
      Moreover, Speg mutant mice exhibited significant neonatal mortality, with
      increased death occurring by 2 days after birth. CONCLUSIONS: These findings
      demonstrate that mutation of the Speg locus leads to cardiac dysfunction and a
      phenotype consistent with a dilated cardiomyopathy.

PMID- 19118251
TI  - Single versus combined blood pressure components and risk for cardiovascular
      disease: the Framingham Heart Study.
AB  - BACKGROUND: The utility of single versus combined blood pressure (BP) components
      in predicting cardiovascular disease (CVD) events is not established. We compared
      systolic BP (SBP) and diastolic BP (DBP) versus pulse pressure (PP) and mean
      arterial pressure (MAP) combined and each of these 4 BP components alone in
      predicting CVD events. METHODS AND RESULTS: In participants in the original
      (n=4760) and offspring (n=4897) Framingham Heart Study who were free of CVD
      events and BP-lowering therapy, 1439 CVD events occurred over serial 4-year
      intervals from 1952 to 2001. In pooled logistic regression with the use of BP
      categories, combining SBP with DBP and PP with MAP improved model fit compared
      with individual BP components (P<0.05 to P<0.0001). Significant interactions were
      noted between SBP and DBP (P=0.02) and between PP and MAP (P=0.01) in their
      respective multivariable models. Models with continuous variables for SBP+DBP and
      PP+MAP proved identical in predicting CVD events (Akaike Information Criteria=10
      625 for both). Addition of a quadratic DBP(2) term to DBP and SBP further
      improved fit (P=0.0016). CONCLUSIONS: Combining PP with MAP and SBP with DBP
      produced models that were superior to single BP components for predicting CVD,
      and the extent of CVD risk varied with the level of each BP component. The
      combination of PP+MAP (unlike SBP+DBP) has a monotonic relation with risk and may
      provide greater insight into hemodynamics of altered arterial stiffness versus
      impaired peripheral resistance but is not superior to SBP+DBP in predicting CVD
      events.

PMID- 19118252
TI  - Mechanisms of aortic and cardiac dysfunction in uremic mice with aortic
      calcification.
AB  - BACKGROUND: Chronic renal failure (CRF) is associated with cardiac dysfunction
      and increased aortic stiffness. The mechanisms involved are not clearly
      understood. We examined changes over time in cardiac and aortic function in a
      murine CRF model. METHODS AND RESULTS: Eight-week-old mice were randomly assigned
      to 1 of 4 groups: wild-type non-CRF, wild-type CRF, apolipoprotein E knockout non
      CRF, and apolipoprotein E knockout CRF. Echocardiography was performed and blood
      samples were taken at baseline and after 6 and 10 weeks of CRF. Vascular
      reactivity and adhesion molecule expression were studied after 6 and 10 weeks of
      CRF. Left ventricular hypertrophy, altered left ventricular relaxation, and
      increased aortic stiffness were observed after 6 weeks of CRF and persisted after
      10 weeks. The 4 groups of mice did not significantly differ in terms of arterial
      blood pressure and aortic structure. The degree of vascular calcification and
      serum total cholesterol concentration were higher in the CRF groups than in the
      non-CRF groups. These changes, however, could not explain the cardiac and
      vascular differences seen in the 2 CRF groups. In contrast, alterations in
      vascular reactivity, the upregulation of adhesion molecule expression, and CRF
      status were significantly associated with these changes. CONCLUSIONS: In a mouse
      model of CRF, left ventricular hypertrophy, cardiac diastolic dysfunction, and
      increased aortic stiffness were not related to structural changes in the aorta
      (including aortic calcification) or high serum cholesterol levels. However,
      cardiac and aortic abnormalities were associated with the extent of
      subendothelial dysfunction and the severity of CRF.

PMID- 19118253
TI  - Derivation and validation of a preoperative prediction rule for delirium after
      cardiac surgery.
AB  - BACKGROUND: Delirium is a common outcome after cardiac surgery. Delirium
      prediction rules identify patients at risk for delirium who may benefit from
      targeted prevention strategies, early identification, and treatment of underlying
      causes. The purpose of the present prospective study was to develop a prediction
      rule for delirium in a cardiac surgery cohort and to validate it in an
      independent cohort. METHODS AND RESULTS: Prospectively, cardiac surgery patients
      > or =60 years of age were enrolled in a derivation sample (n=122) and then a
      validation sample (n=109). Beginning on the second postoperative day, patients
      underwent a standardized daily delirium assessment, and delirium was diagnosed
      according to the confusion assessment method. Delirium occurred in 63 (52%) of
      the derivation cohort patients. Multivariable analysis identified 4 variables
      independently associated with delirium: prior stroke or transient ischemic
      attack, Mini Mental State Examination score, abnormal serum albumin, and the
      Geriatric Depression Scale. Points were assigned to each variable: Mini Mental
      State Examination < or =23 received 2 points, and Mini Mental State Examination
      score of 24 to 27 received 1 point; Geriatric Depression Scale >4, prior
      stroke/transient ischemic attack, and abnormal albumin received 1 point each. In
      the derivation sample, the cumulative incidence of delirium for point levels of
      0, 1, 2, and > or =3 was 19%, 47%, 63%, and 86%, respectively (C statistic,
      0.74). The corresponding incidence of delirium in the validation sample was 18%,
      43%, 60%, and 87%, respectively (C statistic, 0.75). CONCLUSIONS: Delirium occurs
      frequently after cardiac surgery. Using 4 preoperative characteristics,
      clinicians can determine cardiac surgery patients' risk for delirium. Patients at
      higher delirium risk could be candidates for close postoperative monitoring and
      interventions to prevent delirium.

PMID- 19118254
TI  - Pulmonary vascular reactivity and prognosis in patients with chronic
      thromboembolic pulmonary hypertension: a pilot study.
AB  - BACKGROUND: Surgical pulmonary endarterectomy is the preferred treatment for
      chronic thromboembolic pulmonary hypertension. Persistent pulmonary hypertension
      after pulmonary endarterectomy has been recognized as a major determinant of poor
      outcome. We tested whether acute vasoreactivity identifies chronic thromboembolic
      pulmonary hypertension patients prone to develop persistent/recurrent pulmonary
      hypertension after pulmonary endarterectomy and whether the degree of acute
      vasoreactivity affects survival or freedom from lung transplantation. METHODS AND
      RESULTS: Right-sided heart catheterization at baseline and after inhalation of 40
      ppm nitric oxide for 20 minutes was performed in 103 patients (56.3+/-15.3 years
      old, 53 women). Reductions in mean pulmonary arterial pressure (DeltamPAP; -8.8+/
      12.6%; P<0.0001) and pulmonary vascular resistance (-16.1+/-18.1%; P<0.0001) and
      an increase in mixed venous saturation during inhaled nitric oxide (9.1+/-11.6%;
      P<0.0001) were observed. Sixty-two patients underwent pulmonary endarterectomy
      after a median of 49 days (25th and 75th percentiles: 24 and 123 days). Operated
      patients were followed up for a median of 70.9 months (25th and 75th percentiles:
      14 and 97 months). Change in mPAP during inhaled NO was identified as a predictor
      of persistent/recurrent pulmonary hypertension after pulmonary endarterectomy.
      Patients experiencing a reduction in mPAP >10.4% with nitric oxide inhalation had
      a better postoperative outcome. A significant correlation was found between
      DeltamPAP and immediate postoperative pulmonary vascular resistance (r=0.5,
      P<0.0001). CONCLUSIONS: A total of 80 (77.7%) of 103 patients demonstrated acute
      pulmonary vascular reactivity of some degree. A decrease in mPAP >10.4% under
      inhaled nitric oxide is a predictor of long-term survival and freedom from lung
      transplantation in adult patients with chronic thromboembolic pulmonary
      hypertension who are undergoing pulmonary endarterectomy.

PMID- 19118255
TI  - Multipotent mesenchymal stem cells acquire a lymphendothelial phenotype and
      enhance lymphatic regeneration in vivo.
AB  - BACKGROUND: The importance and therapeutic value of stem cells in
      lymphangiogenesis are poorly understood. We evaluated the potential of human and
      murine mesenchymal stem cells (MSCs) to acquire a lymphatic phenotype in vitro
      and to enhance lymphatic regeneration in vivo. METHODS AND RESULTS: We assessed
      the lymphendothelial differentiation of human and murine MSCs after induction
      with supernatant derived from human dermal microvascular endothelial cells,
      isolated lymphatic endothelial cells, and purified vascular endothelial growth
      factor (VEGF)-C in vitro. We used human or murine progenitor MSC lines and then
      characterized the lymphatic phenotype by morphology, migratory capacity, and the
      expression of lymphatic markers such as Prox-1, podoplanin, Lyve-1, VEGF receptor
      2, and VEGF receptor-3. Using a murine lymphatic edema model, we assessed the
      potential of these cells to form a functional lymphatic vasculature in vivo after
      injection of syngeneic MSCs. Incubation with supernatant from lymphatic
      endothelial cells induced an endothelium-like morphology and the expression of
      lymphendothelial markers in both human and murine MSCs in vitro. MSCs showed
      migratory activity along a VEGF-C gradient, which was enhanced by VEGF-C
      conditioning. In vivo, the local application of MSCs resulted in a significant
      decrease in edema formation (-20.1%; P<0.01 versus untreated tails) after 3
      weekly cell injections and restored the drainage of intradermally injected
      methylene blue after 7 weekly injections. CONCLUSIONS: MSCs were capable of
      expressing a lymphatic phenotype when exposed to lymph-inductive media and
      purified VEGF-C. Migratory activity toward VEGF-C in vitro suggests homing
      capability in vivo. Restoration of lymphatic drainage after injection of MSCs in
      a lymphedema model indicates that MSCs play a role in lymphatic regeneration. The
      potential clinical application of MSC in wound healing and reduction of lymphatic
      edema warrants further research.

PMID- 19118256
TI  - Physical activity during daily life and functional decline in peripheral arterial
      disease.
AB  - BACKGROUND: Few modifiable behaviors have been identified that are associated
      with slower rates of functional decline in persons with lower-extremity
      peripheral arterial disease. We determined whether higher levels of physical
      activity during daily life are associated with less functional decline in persons
      with peripheral arterial disease. METHODS AND RESULTS: The study population
      included 203 peripheral arterial disease participants who underwent vertical
      accelerometer-measured physical activity continuously over 7 days and were
      followed up annually for up to 4 years (mean, 33.6 months). Outcomes were average
      annual changes in 6-minute walk performance, usual-paced and fast-paced 4-m
      walking velocity, and the short performance physical battery. Analyses were
      adjusted for age, sex, race, comorbidities, body mass index, ankle brachial
      index, smoking, and walking exercise frequency. Higher baseline physical activity
      levels measured by a vertical accelerometer were associated with significantly
      less average annual decline in 6-minute walk performance (P for trend=0.010),
      fast-paced 4-m walking velocity (P for trend=0.002), and the short performance
      physical battery (P for trend=0.001). Compared with the lowest baseline quartile,
      those in the highest baseline quartile of physical activity had less annual
      decline in 6-minute walk performance (-50.82 versus -107.0 ft/y; P=0.019), fast
      paced 4-m walking speed (-0.0034 versus -0.111 m . s(-1) . y(-1); P=0.002), and
      the short performance physical battery (-0.074 versus -0.829; P=0.005).
      CONCLUSIONS: Higher physical activity levels during daily life are associated
      with less functional decline among people with peripheral arterial disease. These
      findings may be particularly important for the large number of peripheral
      arterial disease persons without access to supervised walking exercise programs.

PMID- 19118257
TI  - Pressure overload-induced alterations in fibrillar collagen content and
      myocardial diastolic function: role of secreted protein acidic and rich in
      cysteine (SPARC) in post-synthetic procollagen processing.
AB  - BACKGROUND: Chronic pressure overload causes myocardial hypertrophy, increased
      fibrillar collagen content, and abnormal diastolic function. We hypothesized that
      one determinant of these pressure overload-induced changes is the extracellular
      processing of newly synthesized procollagen into mature collagen fibrils. We
      further hypothesized that secreted protein acidic and rich in cysteine (SPARC)
      plays a key role in post-synthetic procollagen processing in normal and pressure
      overloaded myocardium. METHODS AND RESULTS: To determine whether pressure
      overload-induced changes in collagen content and diastolic function are affected
      by the absence of SPARC, age-matched wild-type (WT) and SPARC-null mice underwent
      either transverse aortic constriction (TAC) for 4 weeks or served as nonoperated
      controls. Left ventricular (LV) collagen content was measured histologically by
      collagen volume fraction, collagen composition was measured by hydroxyproline
      assay as soluble collagen (1 mol/L NaCl extractable) versus insoluble collagen
      (mature cross-linked collagen), and collagen morphological structure was examined
      by scanning electron microscopy. SPARC expression was measured by immunoblot. LV,
      myocardial, and cardiomyocyte structure and function were assessed by
      echocardiographic, papillary muscle, and isolated cardiomyocyte studies. In WT
      mice, TAC increased LV mass, SPARC expression, myocardial diastolic stiffness,
      fibrillar collagen content, and soluble and insoluble collagen. In SPARC-null
      mice, TAC increased LV mass to an extent similar to WT mice. In addition, in
      SPARC-null mice, TAC increased fibrillar collagen content, albeit significantly
      less than that seen in WT TAC mice. Furthermore, the proportion of LV collagen
      that was insoluble was less in the SPARC-null TAC mice (86+/-2%) than in WT TAC
      mice (99+/-2%, P<0.05), and the proportion of collagen that was soluble was
      greater in the SPARC-null TAC mice (14+/-2%) than in WT TAC mice (1+/-2%, P<0.05)
      As a result, myocardial diastolic stiffness was lower in SPARC-null TAC mice
      (0.075+/-0.005) than in WT TAC mice (0.045+/-0.005, P<0.05). CONCLUSIONS: The
      absence of SPARC reduced pressure overload-induced alterations in extracellular
      matrix fibrillar collagen and diastolic function. These data support the
      hypothesis that SPARC plays a key role in post-synthetic procollagen processing
      and the development of mature cross-linked collagen fibrils in normal and
      pressure-overloaded myocardium.

PMID- 19118259
TI  - Hypoxia induces near-native mechanical properties in engineered heart valve
      tissue.
AB  - BACKGROUND: Previous attempts in heart valve tissue engineering (TE) failed to
      produce autologous valve replacements with native-like mechanical behavior to
      allow for systemic pressure applications. Because hypoxia and insulin are known
      to promote protein synthesis by adaptive cellular responses, a physiologically
      relevant oxygen tension and insulin supplements were applied to the growing heart
      valve tissues to enhance their mechanical properties. METHODS AND RESULTS:
      Scaffolds of rapid-degrading polyglycolic acid meshes coated with poly-4
      hydroxybutyrate were seeded with human saphenous vein myofibroblasts. The tissue
      engineered constructs were cultured under normal oxygen tension (normoxia) or
      hypoxia (7% O(2)) and incubated with or without insulin. Glycosaminoglycan
      production in the constructs approached that of native values under the influence
      of hypoxia and under the influence of insulin. Both insulin and hypoxia were
      associated with enhanced matrix production and improved mechanical properties;
      however, a synergistic effect was not observed. Although the amount of collagen
      and cross-links in the engineered tissues was still lower than that in native
      adult human aortic valves, constructs cultured under hypoxic conditions reached
      native human aortic valve levels of tissue strength and stiffness after 4 weeks
      of culturing. CONCLUSIONS: These results indicate that oxygen tension may be a
      key parameter for the achievement of sufficient tissue quality and mechanical
      integrity in tissue-engineered heart valves. Engineered tissues of such strength,
      based on rapid-degrading polymers, have not been achieved to date. These findings
      bring the potential use of tissue-engineered heart valves for systemic
      applications a step closer and represent an important improvement in heart valve
      tissue engineering.

PMID- 19118258
TI  - High efficacy of beta-blockers in long-QT syndrome type 1: contribution of
      noncompliance and QT-prolonging drugs to the occurrence of beta-blocker treatment
      "failures".
AB  - BACKGROUND: Beta-blocker efficacy in long-QT syndrome type 1 is good but variably
      reported, and the causes of cardiac events despite beta-blocker therapy have not
      been ascertained. METHODS AND RESULTS: This was a retrospective study of the
      details surrounding cardiac events in 216 genotyped long-QT syndrome type 1
      patients treated with beta-blocker and followed up for a median time of 10 years.
      Before beta-blocker, cardiac events occurred in 157 patients (73%) at a median
      age of 9 years, with cardiac arrest (CA) in 26 (12%). QT-prolonging drugs were
      used by 17 patients; 9 of 17 (53%) had CA compared with 17 of 199 nonusers (8.5%;
      odds ratio, 12.0; 95% confidence interval, 4.1 to 35.3; P<0.001). After beta
      blocker, 75% were asymptomatic, and cardiac events were significantly reduced
      (P<0.001), with a median event count (quartile 1 to 3) per person of 0 (0 to 1).
      Twelve patients (5.5%) suffered CA/sudden death, but 11 of 12 (92%) were
      noncompliant (n=8), were on a QT-prolonging drug (n=2), or both (n=1) at the time
      of the event. The risk for CA/sudden death in compliant patients not taking QT
      prolonging drugs was dramatically less compared with noncompliant patients on QT
      prolonging drugs (odds ratio, 0.03; 95% confidence interval, 0.003 to 0.22;
      P=0.001). None of the 26 patients with CA before beta-blocker had CA/sudden death
      on beta-blockers. CONCLUSIONS: beta-Blockers are extremely effective in long-QT
      syndrome type 1 and should be administered at diagnosis and ideally before the
      preteen years. beta-Blocker noncompliance and use of QT-prolonging drug are
      responsible for almost all life-threatening "beta-blocker failures." beta
      Blockers are appropriate therapy for asymptomatic patients and those who have
      never had a CA or beta-blocker therapy. Routine implantation of cardiac
      defibrillators in such patients does not appear justified.

PMID- 19118260
TI  - The Ross procedure: a systematic review and meta-analysis.
AB  - BACKGROUND: Reports on outcome after the Ross procedure are limited by small
      study size and show variable durability results. A systematic review of evidence
      on outcome after the Ross procedure may improve insight into outcome and
      potential determinants. METHODS AND RESULTS: A systematic review of reports
      published from January 2000 to January 2008 on outcome after the Ross procedure
      was undertaken. Thirty-nine articles meeting the inclusion criteria were
      allocated to 3 categories: (1) consecutive series, (2) adult patient series, and
      (3) pediatric patient series. With the use of an inverse variance approach,
      pooled morbidity and mortality rates were obtained. Pooled early mortality for
      consecutive, adult, and pediatric patients series was 3.0% (95% confidence
      interval [CI], 1.8 to 4.9), 3.2% (95% CI, 1.5 to 6.6), and 4.2% (95% CI, 1.4 to
      11.5). Autograft deterioration rates were 1.15% (95% CI, 1.06 to 2.06), 0.78%
      (95% CI, 0.43 to 1.40), and 1.38%/patient-year (95% CI, 0.68 to 2.80),
      respectively, and for right ventricular outflow tract conduit were 0.91% (95% CI,
      0.56 to 1.47), 0.55% (95% CI, 0.26 to 1.17), and 1.60%/patient-year (95% CI, 0.84
      to 3.05), respectively. For studies with mean patient age >18 years versus mean
      patient age < or =18 years, pooled autograft and right ventricular outflow tract
      deterioration rates were 1.14% (95% CI, 0.83 to 1.57) versus 1.69% (95% CI, 1.02
      to 2.79) and 0.65% (95% CI, 0.41 to 1.02) versus 1.66%/patient-year (95% CI, 0.98
      to 2.82), respectively. CONCLUSIONS: The Ross procedure provides satisfactory
      results for both children and young adults. Durability limitations become
      apparent by the end of the first postoperative decade, in particular in younger
      patients.

PMID- 19118261
TI  - Synthesis and functional activity of tRNAs labeled with fluorescent hydrazides in
      the D-loop.
AB  - We describe an optimized procedure for replacing the dihydrouridine residues of
      charged tRNAs with Cy3 and Cy5 dyes linked to a hydrazide group, and demonstrate
      that the labeled molecules are functional in ribosomal activities including 30S
      initiation complex formation, EF-Tu-dependent binding to the ribosome,
      translocation, and polypeptide synthesis. This procedure should be
      straightforwardly generalizable to the incorporation of other hydrazide-linked
      fluorophores into tRNA or other dihydrouridine-containing RNAs. In addition, we
      use a rapid turnover FRET experiment, measuring energy transfer between Cy5
      labeled tRNA(fMet) and Cy3-labeled fMetPhe-tRNA(Phe), to obtain direct evidence
      supporting the hypothesis that the early steps of translocation involve movements
      of the flexible 3'-single-stranded regions of the tRNAs, with the considerable
      increase in the distance separating the two tRNA tertiary cores occurring later
      in the process.

PMID- 19118263
TI  - Gastroesophageal reflux disease is associated with poor asthma control, quality
      of life, and psychological status in Chinese asthma patients.
AB  - BACKGROUND: Both asthma and gastroesophageal reflux disease (GERD) are common,
      often coexist, and have significant impact on a patient's quality of life. Our
      aim was to determine the prevalence of GERD in asthmatic patients at a major
      hospital in Hong Kong, and to examine the impact of GERD and its association with
      asthma control. METHODS: Patients with asthma who attended the respiratory clinic
      at Queen Mary Hospital, Hong Kong, were recruited. Demographic data were
      collected, and a validated Chinese GERD questionnaire was used. The Medical
      Outcomes Study 36-item short form (SF-36) was used to assess quality of life, and
      the Hospital Anxiety and Depression Scale (HADS) was used to assess psychological
      status. Asthma control was assessed by the asthma control test. RESULTS: A total
      of 218 patients were recruited; 40.4% of asthmatic patients (88 patients) had
      GERD, as defined by the GERD questionnaire. Compared with those patients without
      GERD, those with GERD had significantly worse asthma control (p = 0.022), worse
      quality of life in all domains of the SF-36 (all p < 0.01), and more anxiety
      (6.82 vs 4.90, respectively; p < 0.001) and depression (6.09 vs 4.05,
      respectively; p < 0.001) as reflected by HADSs. CONCLUSIONS: A significant
      proportion of asthmatic patients in Hong Kong have GERD, and this is associated
      with poorer asthmatic control, quality of life, and psychological status.

PMID- 19118264
TI  - Safety of maximal cardiopulmonary exercise testing in pediatric patients with
      pulmonary hypertension.
AB  - BACKGROUND: Maximal cardiopulmonary exercise testing (CPX) is valuable to
      quantifying functional capacity in patients with pulmonary hypertension (PH), but
      information on CPX in children is limited possibly because of safety concerns.
      The purpose of this study was to examine the safety of CPX in pediatric patients
      with PH. METHODS: Data were obtained retrospectively from patients referred for
      CPX at our institution between January 2001 and September 2007. Patients with a 6
      min walk distance < 275 m were excluded. Exercise test complications were grouped
      according to ischemic ECG changes, presence of arrhythmia, and oxygen
      desaturation at peak exercise and were graded as mild, moderate, or severe.
      RESULTS: Twenty-seven patients (4 with idiopathic PH, 23 with secondary PH), 12.5
      years of age (range, 6.9 to 18 years), participated in 64 CPX sessions. The mean
      (+/- SD) peak oxygen uptake was 23.3 +/- 5.4 mL/kg/min, with a mean decrease in
      arterial oxygen saturation to 85% +/- 15.7% at peak exercise. Mild arrhythmia was
      detected in 30% of the patients. ST-segment depression was graded as mild (19%)
      or moderate (1.5%). There were no significant adverse events, such as syncope,
      chest pain, or dizziness. CPX was stopped for fatigue in 53% of patients, leg
      fatigue in 23%, dyspnea in 21%, and miscellaneous reasons in 3%. CONCLUSIONS:
      This study suggests that CPX can be performed safely in pediatric patients with
      PH, with the exception of patients with severe limitation who were excluded from
      exercise testing. Although the number of patients in the sample is small, the
      data imply that the absence of significant patient symptoms and low incidence of
      arrhythmia or significant ST-segment depression make CPX a safe choice for
      measuring functional capacity in this patient population.

PMID- 19118262
TI  - Oxidative damage to nucleic acids in severe emphysema.
AB  - BACKGROUND: Oxidative stress is a key element in the pathogenesis of emphysema,
      but oxidation of nucleic acids has been largely overlooked. The aim of this study
      was to investigate oxidative damage to nucleic acids in severe emphysematous
      lungs. METHODS: Thirteen human severe emphysematous lungs, including five with
      alpha(1)-antitrypsin deficiency (AATD), were obtained from patients receiving
      lung transplantation. Control lung tissue was obtained from non-COPD lungs (n =
      8) and donor lungs (n = 8). DNA and RNA oxidation were investigated by
      immunochemistry. Morphometry (mean linear intercept [Lm] and CT scan) and
      immunostaining for CD68 and neutrophil elastase also were performed. RESULTS:
      Nucleic acid oxidation was increased in alveolar wall cells in emphysematous
      lungs compared to non-COPD and donor lungs (p < 0.01). In emphysematous lungs,
      oxidative damage to nucleic acids in alveolar wall cells was increased in the
      more severe emphysematous areas assessed by histology (Lm, > 0.5 mm; p < 0.05)
      and CT scan (< -950 Hounsfield units; p < 0.05). Compared to classic emphysema,
      AATD lungs exhibited higher levels of nucleic acid oxidation in macrophages (p <
      0.05) and airway epithelial cells (p < 0.01). Pretreatments with DNase and RNase
      demonstrated that RNA oxidation was more prevalent than DNA oxidation in alveolar
      wall cells. CONCLUSIONS: We demonstrated for the first time that nucleic acids,
      especially RNA, are oxidized in human emphysematous lungs. The correlation
      between the levels of oxidative damage to nucleic acids in alveolar wall cells
      and the severity of emphysema suggest a potential role in the pathogenesis of
      emphysema.

PMID- 19118265
TI  - Comparative evaluation of two asthma care quality measures among Medicaid
      beneficiaries.
AB  - BACKGROUND: The relative performance of asthma care quality measures has not been
      evaluated in Medicaid populations. METHODS: Using complete claims and
      pharmaceutical data for 19,076 patients with persistent asthma (based on Health
      Effectiveness and Data Information Set criteria) in five Medicaid populations, we
      compared the following two measures of asthma care quality: filling prescriptions
      for controller asthma medications within 1 year and the ratio of controller
      medication to the total number of asthma medication prescriptions filled within 1
      year. We calculated whether meeting each quality measure was associated with
      decreased odds of emergency department (ED) treatment episodes. We then compared
      the odds ratios, receiver operating characteristic (ROC) curves, and deviances
      between models, using each measure to predict ED utilization in Medicaid
      populations. RESULTS: Although meeting each measure was associated with lower
      odds of ED utilization, this decrease was larger if the controller asthma
      medication measure was met rather than the ratio measure. Additionally, models
      using the controller medication measure had greater areas under the ROC curve and
      smaller deviances than models using the ratio measure. CONCLUSIONS: Both
      administrative measures of asthma care quality were associated with lower odds of
      ED utilization. The controller medication measure of asthma care quality may be
      better than the ratio measure in relation to emergency asthma care utilization by
      Medicaid beneficiaries.

PMID- 19118266
TI  - The influence of obstructive sleep apnea and gender on genioglossus activity
      during rapid eye movement sleep.
AB  - BACKGROUND: The mechanisms contributing to worsening of obstructive sleep apnea
      (OSA) during rapid eye movement (REM) sleep have been minimally studied. Reduced
      upper-airway muscle tone may be an important contributor. Because respiratory
      events and the associated blood gas changes can influence genioglossus (GG)
      activity, we compared GG activity between OSA patients and control subjects
      during REM sleep using continuous positive airway pressure (CPAP) to minimize the
      influences of upper-airway resistance (RUA) and blood gas disturbances on GG
      activity. METHODS: Twenty subjects (10 female subjects), 12 healthy individuals,
      and 8 OSA patients, were studied overnight. Sleep staging, epiglottic pressure,
      minute ventilation, and GG electromyogram (GGEMG) were recorded. GGEMG was
      compared between REM sleep with (phasic REM) and without (tonic REM) eye
      movements, non-REM (NREM) sleep, and wakefulness. RESULTS: Breathing frequency
      increased from stable NREM, to tonic REM to phasic REM sleep, whereas tidal
      volume and GGEMG decreased (ie, peak GGEMG: 3.0 +/- 0.7 vs 1.7 +/- 0.4 vs 1.2 +/-
      0.3% max, respectively; p < 0.001). Reductions in GGEMG during REM sleep were not
      different between OSA patients and control subjects or between genders.
      CONCLUSIONS: When RUA and blood gas disturbances are minimized by CPAP,
      genioglossal activity is reduced in a stepwise manner from stable NREM, to tonic
      REM to phasic REM sleep to a similar extent in OSA and healthy individuals of
      both genders. Thus, an inherent abnormality in GG neural control in OSA patients
      during REM sleep is unlikely to explain the increased upper-airway collapse in
      this sleep stage. Rather, a generalized reduction in GG activity during REM
      likely renders individuals who are highly reliant on upper-airway dilator muscles
      vulnerable to pharyngeal collapse during REM sleep.

PMID- 19118267
TI  - Application of endobronchial ultrasound-guided transbronchial needle aspiration
      following integrated PET/CT in mediastinal staging of potentially operable non
      small cell lung cancer.
AB  - BACKGROUND: The role of endobronchial ultrasound-guided transbronchial needle
      aspiration (EBUS-TBNA) following integrated PET/CT scanning in mediastinal
      staging of non-small cell lung cancer (NSCLC) has not been assessed. METHODS: We
      prospectively evaluated the diagnostic values of PET/CT scanning and EBUS-TBNA
      for mediastinal staging in 117 patients with potentially operable NSCLC with
      accessible mediastinal lymph nodes (diameter range, 5 to 20 mm) by EBUS-TBNA.
      Subgroup analysis according to histologic type was performed. RESULTS: Of 30
      cases of mediastinal metastasis, 27 were confirmed by EBUS-TBNA and 3 were
      confirmed by surgery. EBUS-TBNA results confirmed all cases with true-positive
      PET/CT scan findings and six of nine cases with false-negative PET/CT scan
      findings. The sensitivity, specificity, positive predictive value, negative
      predictive value (NPV), and accuracy of EBUS-TBNA in the detection of mediastinal
      metastasis were 90.0%, 100%, 100%, 96.7%, and 97.4%, respectively. For PET/CT
      scans, the values were 70.0%, 59.8%, 37.5%, 85.2%, and 62.4%, respectively (p =
      0.052; p < 0.001; p < 0.001; p = 0.011; p < 0.001, respectively). In
      adenocarcinoma (n = 55), EBUS-TBNA detected four of six cases with false-negative
      PET/CT scan findings, and the NPV was higher for EBUS-TBNA than for PET/CT scans
      (94.6% vs 77.8%, respectively; p = 0.044). In squamous cell carcinoma (n = 53),
      the NPV of EBUS-TBNA and PET/CT scans were similarly high (97.9% vs 96.3%,
      respectively; p = 0.689). CONCLUSIONS: EBUS-TBNA was an effective invasive method
      following PET/CT scanning in the mediastinal staging of potentially operable
      NSCLC. In mediastinal PET/CT scan-positive cases, EBUS-TBNA was an excellent tool
      for detecting mediastinal metastasis. Even in mediastinal PET/CT scan-negative
      cases, EBUS-TBNA can be useful for confirming mediastinal metastases, especially
      in adenocarcinoma.

PMID- 19118268
TI  - Prolonged acute mechanical ventilation: implications for hospital benchmarking.
AB  - BACKGROUND: Hospital performance measures rely on aggregate outcomes. For
      patients receiving mechanical ventilation (MV), outcomes depend on severity of
      illness, hospital MV volume, and case mix. Patients requiring prolonged acute MV
      (PAMV) [MV for >or= 96 h] comprise a resource-intensive group, but the impact of
      its volume on aggregate outcomes is unknown. We investigated whether observed
      outcomes differed from those predicted by APACHE (acute physiology and chronic
      health evaluation) IV risk adjustment and the relationship between hospital MV
      volume and outcomes among patients receiving PAMV. METHODS: We conducted a
      retrospective cohort study using the APACHE IV database between the years 2001
      and 2005. RESULTS: Of the 94,553 patients receiving MV at 45 hospitals, 24,366
      (25.8%) were receiving PAMV. Unadjusted mortality was 32.3% for patients
      receiving PAMV and 22.9% for patients receiving short-term MV (STMV) [< 96 h].
      Although mortality predictions were accurate in both groups, the length-of-stay
      (LOS) predictions underestimated duration of MV, ICU LOS, and hospital LOS by
      5.2, 4.6, and 5.4 days, respectively, in the PAMV group. After stratifying the
      PAMV group by hospital MV volume, except for quintile 1, the standardized
      mortality ratio (SMR) was found to be inversely related to the volume quintile.
      The difference between actual and predicted MV durations, however, exhibited a
      consistent direct relationship with the MV volume. CONCLUSIONS: In patients
      requiring PAMV, the SMR is inversely proportional to hospital MV volume.
      Conversely, the PAMV group had a disproportionate effect on durations of MV, ICU
      LOS, and hospital LOS, and these marginal excesses increased with the hospital MV
      volume quintile. Development of specific predictive equations for patients
      receiving PAMV is recommended. Benchmarking measures must consider the case mix
      of patients receiving STMV vs those receiving PAMV.

PMID- 19118269
TI  - Association of IL-17RB gene polymorphism with asthma.
AB  - BACKGROUND: Interleukin (IL)-17E is a member of the IL-17 family, which induces
      IL-4, IL-5, IL-13, and eotaxin in experimental animals via IL-17 receptor B (IL
      17RB). The activation of IL-17RB amplifies allergic-type inflammatory responses
      by inducing Jun kinase (or JNK), p38 mitogen-activated protein kinase (or MAPK),
      and nuclear factor-kappaB. OBJECTIVES: We examined the association of
      polymorphisms in the IL-17RB gene with asthma susceptibility and investigated the
      effects of those polymorphisms on the transcription of various IL-17RB isoforms.
      METHODS: In total, 954 asthmatic patients or 265 healthy control subjects were
      screened for polymorphisms in IL-17RB by single-base extension. The messenger RNA
      expression IL-17RB in B-cell lines derived from patients was also measured by
      reverse transcription-polymerase chain reaction. RESULTS: Direct sequencing of 24
      unrelated Korean DNA samples revealed 18 genetic variants, including four
      insertion/deletions and 14 single-nucleotide polymorphisms (SNPs). Six of the
      SNPs (-1465G>A, +5661G>A, +6297T>C [Y123Y], +13797C>T, +18661C>T, and +18965G>A)
      were used to screen a larger group of subjects. Intronic polymorphism +5661G>A
      was significantly associated with the development of asthma (p = 0.001);
      moreover, a minor allele of IL-17RB +5661G>A appeared at a lower frequency in the
      asthmatic patients than in the healthy control subjects (0.13 vs 0.19,
      respectively). The IL-17RB messenger RNA expression in B cells homozygous for IL
      17RB+ 5661GG was significantly higher than that in B cells homozygous for IL
      17RB+5661AA (p = 0.002). CONCLUSIONS: A rare allele of IL-17RB +5661G>A may have
      a protective role against the development of asthma via regulation at the level
      of transcription. The SNPs identified in this study may be used to develop
      markers to assess the risk of asthma.

PMID- 19118270
TI  - Treatment of sarcoidosis-associated pulmonary hypertension. A two-center
      experience.
AB  - BACKGROUND: Pulmonary hypertension (PH) is a common complication of sarcoidosis
      that is associated with increased mortality. The pathogenesis of PH in
      sarcoidosis is uncertain, and the role of pulmonary arterial hypertension (PAH)
      specific therapies remains to be determined. METHODS: We conducted a
      retrospective study of patients with sarcoidosis and PH at two referral centers.
      New York Heart Association (NYHA) functional class, exercise capacity,
      hemodynamic data, pulmonary function tests, and survival were collected and
      analyzed. RESULTS: Twenty-two sarcoidosis patients treated with PAH-specific
      therapies were identified. After a median of 11 months of follow-up, NYHA class
      was improved in nine subjects. Mean 6-min walk distance (n = 18) increased by 59
      m (p = 0.032). Patients with a higher FVC experienced a greater increment in
      exercise capacity. Among 12 patients with follow-up hemodynamic data, mean
      pulmonary artery pressure was reduced from 48.5 +/- 4.3 to 39.4 +/- 2.8 mm Hg (p
      = 0.008). The 1- and 3-year transplant-free survival rates were 90% and 74%,
      respectively. CONCLUSIONS: PAH-specific therapy may improve functional class,
      exercise capacity, and hemodynamics in PH associated with sarcoidosis.
      Prospective, controlled trials of PAH therapies for sarcoidosis are warranted to
      verify this apparent benefit. Mortality among the study population was high,
      highlighting the need for urgent evaluation at a lung transplant center.

PMID- 19118271
TI  - Distinguishing obstructive from central sleep apnea events: diaphragm
      electromyogram and esophageal pressure compared.
AB  - BACKGROUND: Distinguishing central sleep apnea (CSA) from obstructive sleep apnea
      (OSA) can be clinically important because different types of apnea may require
      different treatment approaches. Academically, this distinction is important for
      investigating the pathological mechanism of different types of sleep apnea.
      Conventional polysomnography (PSG) with recording of chest and abdominal movement
      may overestimate the frequency of CSA, leading to inappropriate treatment of
      sleep-disordered breathing. We hypothesized that diaphragm electromyogram (EMGdi)
      could be a useful technique to assess neural respiratory drive and respiratory
      effort and, therefore, to distinguish accurately CSA from OSA. METHODS: A
      multipair esophageal electrode catheter mounted with a balloon was used to record
      the EMGdi and esophageal pressure (Pes) during overnight PSG. Nineteen patients
      were included in the study, 12 of whom had previously been identified as having
      central apnea-hypopnea on a diagnostic PSG undertaken for symptoms that suggest
      OSA and 7 of whom were known to have heart failure. RESULTS: A good relationship
      was found between the swing of Pes and the root mean (+/- SD) square of the EMGdi
      during OSA events (0.89 +/- 0.10). About one third of CSA events diagnosed by
      uncalibrated respiratory inductance plethysmography could not be confirmed by Pes
      or EMGdi. No difference was found in the number of CSAs diagnosed by Pes (1,319)
      vs EMGdi (1,293; p > 0.01). CONCLUSIONS: We conclude that both Pes and EMGdi
      measurements are useful in accurately differentiating central from obstructive
      respiratory events. Conventional PSG with recording of chest and abdominal
      movement overestimates the frequency of CSA events.

PMID- 19118272
TI  - Grading of pulmonary right-to-left shunt with transthoracic contrast
      echocardiography: does it predict the indication for embolotherapy?
AB  - RATIONALE: Pulmonary arteriovenous malformations (PAVMs) are associated with
      severe neurologic complications in patients with hereditary hemorrhagic
      telangiectasia (HHT). Therefore, screening is warranted. Transthoracic contrast
      echocardiography (TTCE) can effectively detect a pulmonary right-to-left shunt
      (RLS). OBJECTIVES: To determine prospectively the predictive value of TTCE
      grading to detect PAVMs on high-resolution CT (HRCT) scans of the chest and the
      indication for embolotherapy. METHODS: Three hundred seventeen patients, referred
      for possible HHT, were screened for PAVMs. Patients who underwent both chest HRCT
      scanning and TTCE were included in the study (n = 281). For the purposes of this
      study we used a 3-point grading scale, and shunt grades 3 and 4 according to the
      classification model of Barzilai et al were combined. Embolotherapy was performed
      of all PAVMs judged large enough for treatment. RESULTS: Echocardiographic
      criteria for a pulmonary RLS were present in 105 patients (41%) [mean (+/- SD)
      age, 43.7 +/- 15.7 years; female gender, 63%]. Chest HRCT scan findings were
      positive in 55 patients (52%) in this group. The positive predictive value of
      shunt grade for the presence of PAVMs on chest HRCT scans was 22.9% for grade 1
      (n = 35), 34.8% for grade 2 (n = 23), and 83.0% for grade 3 (n = 47),
      respectively. None of the patients with PAVMs seen on chest HRCT scans and a TTCE
      grade 1 (n = 8) or 2 (n = 8) were candidates for embolotherapy. Of 39 patients
      with TTCE grade 3 and PAVMs seen on chest HRCT scans, 26 patients (67%) underwent
      embolotherapy. CONCLUSION: An increased echocardiographic shunt grade correlates
      with an increased probability of PAVMs seen on chest HRCT scans. Only patients
      with a TTCE grade 3 displayed PAVMs on chest HRCT scans that were large enough
      for embolotherapy.

PMID- 19118274
TI  - ARDS: a clinicopathological confrontation.
AB  - BACKGROUND: The heterogeneity of populations meeting criteria for ARDS may
      explain in part why no specific treatment has yet been shown to decrease
      mortality. To define the pathologic alterations associated with the syndrome,
      particularly the typical pattern of diffuse alveolar damage (DAD), and to
      evaluate whether etiologies or precipitating factors were missed, we evaluated
      patients who died with a clinical diagnosis of ARDS and who had a postmortem
      examination. METHODS: We conducted a 3-year (2002 to 2004) review of all patients
      with ARDS (using the American-European Consensus Conference criteria) who died in
      our ICU and had a postmortem examination. Discrepancies between antemortem and
      postmortem diagnoses were classified as major and minor using the Goldman
      classification. RESULTS: Of 9,184 hospital admissions, 376 patients had a
      clinical diagnosis of ARDS. Of these, 169 died; 69 had a postmortem examination,
      and 64 of these had complete data for analysis. The main cause of death was
      multiple organ failure (27 of 64 patients). Postmortem examination revealed DAD
      in 32 patients (50%), pneumonia without DAD in 16 patients (25%), and invasive
      pulmonary aspergillosis in 8 patients (12.5%). Major unexpected findings were
      found in 15 patients (23%): 7 Goldman class I (including 4 cases of invasive
      pulmonary aspergillosis and 1 of disseminated tuberculosis) and 8 Goldman class
      II. CONCLUSIONS: In this study, ARDS remains a heterogeneous syndrome because
      only half of patients with ARDS had typical DAD. Open lung biopsy, if performed,
      might have led to appropriate therapy and potentially better outcome in five of
      the patients.

PMID- 19118275
TI  - Validity of asthma control test for asthma control assessment in Chinese primary
      care settings.
AB  - OBJECTIVE: To evaluate the validity of the Asthma Control Test (ACT) for
      assessing clinical asthma control in Chinese patients in primary care settings.
      METHODS: This multicenter study involved 403 asthma patients from 15 primary care
      settings in China, who had completed the ACT, Asthma Control Questionnaire (ACQ),
      and spirometry testing. According to the rating of asthma control by asthma
      specialists in line with the Global Initiative for Asthma 2006 guidelines,
      patients were divided into uncontrolled, partly controlled, and controlled groups
      to evaluate the reliability, empirical validity, and screening accuracy of the
      ACT. The screening accuracy of the ACT and ACQ was analyzed comparatively, and
      the asthma control levels rated by the patients and the specialists were also
      compared. RESULTS: The five-item ACT had an internal consistency reliability of
      0.861 and a correlation coefficient with the specialists' rating of 0.697. The
      ACT scores showed significant differences between different levels of FEV(1)
      percent predicted (F = 37.59; p < 0.0001) and specialists' ratings of asthma
      control (F = 169.53; p < 0.0001), and also between patients requiring different
      treatment adjustments (F = 111.33; p < 0.0001). The asthma was controlled for an
      ACT score of >/= 20, partly controlled for scores of 19 and 18, and uncontrolled
      for a score of </= 17. The ACT showed similar percentages of correctly classified
      results with ACQ. The patients' self-rated asthma control level was significantly
      higher than that rated by the specialists (z = 5.93; p < 0.0001). CONCLUSIONS:
      The ACT is reliable, valid, and practicable for asthma control assessment in
      Chinese patients in the primary care setting.

PMID- 19118273
TI  - Leukotriene pathways and in vitro adenotonsillar cell proliferation in children
      with obstructive sleep apnea.
AB  - INTRODUCTION: The abundant expression of leukotrienes (LTs) and their receptors
      in adenotonsillar tissues of children with obstructive sleep apnea (OSA) suggest
      that LT antagonists could be useful in treating OSA. METHODS: The effects of LTD4
      and of LT receptor antagonists zileuton, montelukast, and BAY u9773 were examined
      on mixed cell cultures prepared from dissociated tonsils or adenoids harvested
      intraoperatively from children with polysomnographically diagnosed OSA.
      Proliferation was assessed by (3)[H]-thymidine incorporation, and inflammatory
      cytokine production (tumor necrosis factor [TNF]-alpha, interleukin [IL]-6, IL-8,
      IL-10, and IL-12) was assessed in supernatants using enzyme-linked immunosorbent
      assay. RESULTS: LTD4 elicited dose-dependent increases in adenotonsillar cell
      proliferation (p < 0.001; n = 12). All LT antagonists exhibited dose-dependent
      reductions in adenotonsillar cellular proliferation rates, with montelukast more
      than BAY u9773 more than zileuton (n = 14/group; p < 0.001). However, BAY u9773
      showed partial agonist effects and increased cellular proliferation at higher
      concentrations (10(-4) mmol/L; p < 0.01; n = 12). LTD4 effects were partially
      blocked by montelukast and BAY u9773 but not by zileuton. All three antagonists
      reduced TNF-alpha, IL-6, and IL-12 concentrations, with selective changes in IL-8
      and no effects on IL-10 levels. CONCLUSIONS: LT pathways mediate intrinsic
      proliferative and inflammatory signaling pathways in adenotonsillar tissues from
      children with OSA, and targeted pharmacologic disruption of these pathways may
      provide nonsurgical alternatives for prevention and treatment of this disease.

PMID- 19118276
TI  - Diffuse pulmonary arteriovenous malformations in hereditary hemorrhagic
      telangiectasia: long-term results of embolization according to the extent of lung
      involvement.
AB  - OBJECTIVES: To review the safety of embolization in patients affected with
      hereditary hemorrhagic telangiectasia (HHT) presenting with diffuse pulmonary
      arteriovenous malformations (PAVMs). To correlate the initial presentation and
      long-term results of embolization according to the distribution of PAVMs.
      MATERIALS AND METHODS: All consecutively treated patients were divided into three
      groups, according to the involvement of every subsegmental pulmonary artery
      (group 1), segmental artery (group 2), or both (group 3) of at least one lobe.
      Age, sex, initial clinical presentation, and Pao(2) were recorded before
      embolization. Per and postprocedural complications were carefully recorded.
      Clinical outcome and imaging follow-up were obtained at 6 months and annually
      thereafter. RESULTS: Thirty-nine patients (31 women, 8 men; mean age, 35 years),
      all of them with bilateral lung involvement, were treated. Group 1 consisted of
      8, group 2 of 17, and group 3 of 14 patients. Dyspnea was present in 35 of the
      patients (90%) and cyanosis in 17 patients (44%). Preembolization Pao(2) was
      different between groups 1 (52.6 +/- 11.6 mm Hg) and 3 (70.7 +/- 14.1 mm Hg).
      Neurologic events were more frequently reported before treatment in group 1
      (62.5%) than in group 2 (35%) or in group 3 (43%). Eighty percent of patients
      reported improvement in their dyspnea after embolization. Pao(2) levels improved
      more in group 2 than in groups 1 and 3. Eight ischemic or infectious
      complications occurred in 4 patients (10%) due to reperfusion of embolized PAVMs
      or enlargement of non-embolized PAVMs. Complete and partial treatment success was
      reported using CT scanning in 59% and 38% of cases, respectively. CONCLUSION:
      Dyspnea and paradoxical embolism are frequently encountered in HHT patients with
      diffuse PAVMs. Prevention of complications and improvement of dyspnea can be
      achieved after successful embolization in most patients. Better improvement of
      Pao(2) can be achieved in group 2.

PMID- 19118277
TI  - Voltage sensor charge loss accounts for most cases of hypokalemic periodic
      paralysis.
AB  - BACKGROUND: Several missense mutations of CACNA1S and SCN4A genes occur in
      hypokalemic periodic paralysis. These mutations affect arginine residues in the
      S4 voltage sensors of the channel. Approximately 20% of cases remain genetically
      undefined. METHODS: We undertook direct automated DNA sequencing of the S4
      regions of CACNA1S and SCN4A in 83 cases of hypokalemic periodic paralysis.
      RESULTS: We identified reported CACNA1S mutations in 64 cases. In the remaining
      19 cases, mutations in SCN4A or other CACNA1S S4 segments were found in 10,
      including three novel changes and the first mutations in channel domains I
      (SCN4A) and III (CACNA1S). CONCLUSIONS: All mutations affected arginine residues,
      consistent with the gating pore cation leak hypothesis of hypokalemic periodic
      paralysis. Arginine mutations in S4 segments underlie 90% of hypokalemic periodic
      paralysis cases.

PMID- 19118278
TI  - Response to the letter by Rose et al.

PMID- 19118279
TI  - Serotonin 5-HT2B receptor in cardiac fibroblast contributes to cardiac
      hypertrophy: a new therapeutic target for heart failure?

PMID- 19118280
TI  - Suppression of peroxisome proliferator-activated receptor-gamma activity by
      angiotensin II in vascular smooth muscle involves Bcr kinase: the fire that
      drowns the water.

PMID- 19118281
TI  - O-linked beta-N-acetylglucosamine: a new piece of the cardioprotection puzzle?

PMID- 19118282
TI  - A new look at the eye: aldosterone and mineralocorticoid receptors as novel
      targets in retinal vasculopathy.

PMID- 19118283
TI  - Transcriptional and posttranslational modifications of titin: implications for
      diastole.

PMID- 19118284
TI  - Developmental basis for electrophysiological heterogeneity in the ventricular and
      outflow tract myocardium as a substrate for life-threatening ventricular
      arrhythmias.
AB  - Reentry is the main mechanism of life-threatening ventricular arrhythmias,
      including ventricular fibrillation and tachycardia. Its occurrence depends on the
      simultaneous presence of an arrhythmogenic substrate (a preexisting condition)
      and a "trigger," and is favored by electrophysiological heterogeneities. In the
      adult heart, electrophysiological heterogeneities of the ventricle exist along
      the apicobasal, left-right, and transmural axes. Also, conduction is
      preferentially slowed in the right ventricular outflow tract, especially during
      pharmacological sodium channel blockade. We propose that the origin of
      electrophysiological heterogeneities of the adult heart lies in early heart
      development. The heart is formed from several progenitor regions: the first heart
      field predominantly forms the left ventricle, whereas the second heart field
      forms the right ventricle and outflow tract. Furthermore, the embryonic outflow
      tract consists of slowly conducting tissue until it is incorporated into the
      ventricles and develops rapidly conducting properties. The subepicardial myocytes
      and subendocardial myocytes run distinctive gene programs from their formation
      onwards. This review discusses the hypothesis that electrophysiological
      heterogeneities in the adult heart result from persisting patterns in gene
      expression and function along the craniocaudal and epicardial-endocardial axes of
      the developing heart. Understanding the developmental origins of
      electrophysiological heterogeneity contributing to ventricular arrhythmias may
      give rise to new therapies.

PMID- 19118285
TI  - The American Diabetes Association (ADA) has been actively involved in the
      development and dissemination of diabetes care standards, guidelines, and related
      documents for many years. Introduction.

PMID- 19118287
TI  - Summary of revisions for the 2009 Clinical Practice Recommendations.

PMID- 19118288
TI  - Executive summary: standards of medical care in diabetes--2009.

PMID- 19118289
TI  - Diagnosis and classification of diabetes mellitus.

PMID- 19118286
TI  - Standards of medical care in diabetes--2009.

PMID- 19118290
TI  - Diabetes care in the school and day care setting.

PMID- 19118291
TI  - Diabetes management in correctional institutions.

PMID- 19118292
TI  - Diabetes and employment.

PMID- 19118293
TI  - Third-party reimbursement for diabetes care, self-management education, and
      supplies.

PMID- 19118297
TI  - List of position statements.

PMID- 19118298
TI  - Images in clinical medicine. Monocular paralysis of vertical ductions after
      facial trauma.

PMID- 19118294
TI  - National standards for diabetes self-management education.

PMID- 19118299
TI  - Communicating medical news--pitfalls of health care journalism.

PMID- 19118300
TI  - The many causes of severe congenital neutropenia.

PMID- 19118301
TI  - Machine perfusion or cold storage in deceased-donor kidney transplantation.
AB  - BACKGROUND: Static cold storage is generally used to preserve kidney allografts
      from deceased donors. Hypothermic machine perfusion may improve outcomes after
      transplantation, but few sufficiently powered prospective studies have addressed
      this possibility. METHODS: In this international randomized, controlled trial, we
      randomly assigned one kidney from 336 consecutive deceased donors to machine
      perfusion and the other to cold storage. All 672 recipients were followed for 1
      year. The primary end point was delayed graft function (requiring dialysis in the
      first week after transplantation). Secondary end points were the duration of
      delayed graft function, delayed graft function defined by the rate of the
      decrease in the serum creatinine level, primary nonfunction, the serum creatinine
      level and clearance, acute rejection, toxicity of the calcineurin inhibitor, the
      length of hospital stay, and allograft and patient survival. RESULTS: Machine
      perfusion significantly reduced the risk of delayed graft function. Delayed graft
      function developed in 70 patients in the machine-perfusion group versus 89 in the
      cold-storage group (adjusted odds ratio, 0.57; P=0.01). Machine perfusion also
      significantly improved the rate of the decrease in the serum creatinine level and
      reduced the duration of delayed graft function. Machine perfusion was associated
      with lower serum creatinine levels during the first 2 weeks after transplantation
      and a reduced risk of graft failure (hazard ratio, 0.52; P=0.03). One-year
      allograft survival was superior in the machine-perfusion group (94% vs. 90%,
      P=0.04). No significant differences were observed for the other secondary end
      points. No serious adverse events were directly attributable to machine
      perfusion. CONCLUSIONS: Hypothermic machine perfusion was associated with a
      reduced risk of delayed graft function and improved graft survival in the first
      year after transplantation. (Current Controlled Trials number, ISRCTN83876362.)

PMID- 19118302
TI  - Decontamination of the digestive tract and oropharynx in ICU patients.
AB  - BACKGROUND: Selective digestive tract decontamination (SDD) and selective
      oropharyngeal decontamination (SOD) are infection-prevention measures used in the
      treatment of some patients in intensive care, but reported effects on patient
      outcome are conflicting. METHODS: We evaluated the effectiveness of SDD and SOD
      in a crossover study using cluster randomization in 13 intensive care units
      (ICUs), all in The Netherlands. Patients with an expected duration of intubation
      of more than 48 hours or an expected ICU stay of more than 72 hours were
      eligible. In each ICU, three regimens (SDD, SOD, and standard care) were applied
      in random order over the course of 6 months. Mortality at day 28 was the primary
      end point. SDD consisted of 4 days of intravenous cefotaxime and topical
      application of tobramycin, colistin, and amphotericin B in the oropharynx and
      stomach. SOD consisted of oropharyngeal application only of the same antibiotics.
      Monthly point-prevalence studies were performed to analyze antibiotic resistance.
      RESULTS: A total of 5939 patients were enrolled in the study, with 1990 assigned
      to standard care, 1904 to SOD, and 2045 to SDD; crude mortality in the groups at
      day 28 was 27.5%, 26.6%, and 26.9%, respectively. In a random-effects logistic
      regression model with age, sex, Acute Physiology and Chronic Health Evaluation
      (APACHE II) score, intubation status, and medical specialty used as covariates,
      odds ratios for death at day 28 in the SOD and SDD groups, as compared with the
      standard-care group, were 0.86 (95% confidence interval [CI], 0.74 to 0.99) and
      0.83 (95% CI, 0.72 to 0.97), respectively. CONCLUSIONS: In an ICU population in
      which the mortality rate associated with standard care was 27.5% at day 28, the
      rate was reduced by an estimated 3.5 percentage points with SDD and by 2.9
      percentage points with SOD. (Controlled Clinical Trials number, ISRCTN35176830.)

PMID- 19118303
TI  - A syndrome with congenital neutropenia and mutations in G6PC3.
AB  - BACKGROUND: The main features of severe congenital neutropenia are the onset of
      severe bacterial infections early in life, a paucity of mature neutrophils, and
      an increased risk of leukemia. In many patients, the genetic causes of severe
      congenital neutropenia are unknown. METHODS: We performed genomewide genotyping
      and linkage analysis on two consanguineous pedigrees with a total of five
      children affected with severe congenital neutropenia. Candidate genes from the
      linkage interval were sequenced. Functional assays and reconstitution experiments
      were carried out. RESULTS: All index patients were susceptible to bacterial
      infections and had very few mature neutrophils in the bone marrow; structural
      heart defects, urogenital abnormalities, and venous angiectasia on the trunk and
      extremities were additional features. Linkage analysis of the two index families
      yielded a combined multipoint lod score of 5.74 on a linkage interval on
      chromosome 17q21. Sequencing of G6PC3, the candidate gene encoding glucose-6
      phosphatase, catalytic subunit 3, revealed a homozygous missense mutation in exon
      6 that abolished the enzymatic activity of glucose-6-phosphatase in all affected
      children in the two families. The patients' neutrophils and fibroblasts had
      increased susceptibility to apoptosis. The myeloid cells showed evidence of
      increased endoplasmic reticulum stress and increased activity of glycogen
      synthase kinase 3beta (GSK-3beta). We identified seven additional, unrelated
      patients who had severe congenital neutropenia with syndromic features and
      distinct biallelic mutations in G6PC3. CONCLUSIONS: Defective function of glucose
      6-phosphatase, catalytic subunit 3, underlies a severe congenital neutropenia
      syndrome associated with cardiac and urogenital malformations.

PMID- 19118305
TI  - Radiation therapy for early-stage breast cancer after breast-conserving surgery.

PMID- 19118304
TI  - Giant osteoclast formation and long-term oral bisphosphonate therapy.
AB  - BACKGROUND: Bisphosphonates decrease bone resorption and are commonly used to
      treat or prevent osteoporosis. However, the effect of bisphosphonates on their
      target cells remains enigmatic, since in patients benefiting from therapy, little
      change, if any, has been observed in the number of osteoclasts, which are the
      cells responsible for bone resorption. METHODS: We examined 51 bone-biopsy
      specimens obtained after a 3-year, double-blind, randomized, placebo-controlled,
      dose-ranging trial of oral alendronate to prevent bone resorption among healthy
      postmenopausal women 40 through 59 years of age. The patients were assigned to
      one of five groups: those receiving placebo for 3 years; alendronate at a dose of
      1, 5, or 10 mg per day for 3 years; or alendronate at a dose of 20 mg per day for
      2 years, followed by placebo for 1 year. Formalin-fixed, undecalcified planar
      sections were assessed by bone histomorphometric methods. RESULTS: The number of
      osteoclasts was increased by a factor of 2.6 in patients receiving 10 mg of
      alendronate per day for 3 years as compared with the placebo group (P<0.01).
      Moreover, the number of osteoclasts increased as the cumulative dose of the drug
      increased (r=0.50, P<0.001). Twenty-seven percent of these osteoclasts were giant
      cells with pyknotic nuclei that were adjacent to superficial resorption cavities.
      Furthermore, giant, hypernucleated, detached osteoclasts with 20 to 40 nuclei
      were found after alendronate treatment had been discontinued for 1 year. Of these
      large cells, 20 to 37% were apoptotic, according to both their morphologic
      features and positive findings from in situ end labeling. CONCLUSIONS: Long-term
      alendronate treatment is associated with an increase in the number of
      osteoclasts, which include distinctive giant, hypernucleated, detached
      osteoclasts that are undergoing protracted apoptosis.

PMID- 19118306
TI  - Images in clinical medicine. Chondrocalcinosis and hypomagnesemia.

PMID- 19118307
TI  - Clinical problem-solving. Keeping an open mind.

PMID- 19118308
TI  - Organ procurement and perfusion before transplantation.

PMID- 19118309
TI  - The deceiving appearances of osteoclasts.

PMID- 19118310
TI  - Does the Trojan horse have an Achilles' heel?

PMID- 19118311
TI  - Calcific aortic stenosis.

PMID- 19118312
TI  - Analyses of cancer data from three ezetimibe trials.

PMID- 19118313
TI  - Lung cancer.

PMID- 19118314
TI  - Persistent fainting after implantation of a "curative" pacemaker.

PMID- 19118315
TI  - Reports of esophageal cancer with oral bisphosphonate use.

PMID- 19118316
TI  - Antidepressants on trial: how valid is the evidence?
AB  - A recent meta-analysis concluded that newer antidepressant drugs are equivalent
      to or no better than placebos, a conclusion at some variance with their commonly
      judged clinical effectiveness. The 'disconnect' between randomised controlled
      trials and clinical practice would benefit from dissection of contributing
      factors, and redressing limitations to current trial procedures.

PMID- 19118318
TI  - Lamotrigine for treatment of bipolar depression: independent meta-analysis and
      meta-regression of individual patient data from five randomised trials.
AB  - BACKGROUND: There is uncertainty about the efficacy of lamotrigine in bipolar
      depressive episodes. AIMS: To synthesise the evidence for the efficacy of
      lamotrigine in bipolar depressive episodes. METHOD: Systematic review and meta
      analysis of individual patient data from randomised controlled trials comparing
      lamotrigine with placebo. RESULTS: Individual data from 1072 participants from
      five randomised controlled trials were obtained. More individuals treated with
      lamotrigine than placebo responded to treatment on both the Hamilton Rating Scale
      for Depression (HRSD) (relative risk (RR)=1.27, 95% CI 1.09-1.47, P=0.002) and
      Montgomery-Asberg Depression Rating Scale (MADRS) (RR=1.22, 95% CI 1.06-1.41,
      P=0.005). There was an interaction (P=0.04) by baseline severity of depression:
      lamotrigine was superior to placebo in people with HRSD score >24 (RR=1.47, 95%
      CI 1.16-1.87, P=0.001) but not in people with HRSD score < or =24 (RR=1.07, 95%
      CI 0.90-1.27, P=0.445). CONCLUSIONS: There is consistent evidence that
      lamotrigine has a beneficial effect on depressive symptoms in the depressed phase
      of bipolar disorder. The overall pool effect was modest, although the advantage
      over placebo was larger in more severely depressed participants.

PMID- 19118319
TI  - Excess mortality, causes of death and prognostic factors in anorexia nervosa.
AB  - BACKGROUND: Anorexia nervosa is a mental disorder with high mortality. AIMS: To
      estimate standardised mortality ratios (SMRs) and to investigate potential
      prognostic factors. METHOD: Six thousand and nine women who had in-patient
      treatment for anorexia nervosa were followed-up retrospectively using Swedish
      registers. RESULTS: The overall SMR for anorexia nervosa was 6.2 (95% CI 5.5
      7.0). Anorexia nervosa, psychoactive substance use and suicide had the highest
      SMR. The SMR was significantly increased for almost all natural and unnatural
      causes of death. The SMR 20 years or more after the first hospitalisation
      remained significantly high. Lower mortality was found during the last two
      decades. Younger age and longer hospital stay at first hospitalisation was
      associated with better outcome, and psychiatric and somatic comorbidity worsened
      the outcome. CONCLUSIONS: Anorexia nervosa is characterised by high lifetime
      mortality from both natural and unnatural causes. Assessment and treatment of
      psychiatric comorbidity, especially alcohol misuse, may be a pathway to better
      long-term outcome.

PMID- 19118320
TI  - Beyond the critical period: longitudinal study of 8-year outcome in first-episode
      non-affective psychosis.
AB  - BACKGROUND: The critical period hypothesis proposes that deterioration occurs
      aggressively during the early years of psychosis, with relative stability
      subsequently. Thus, interventions that shorten the duration of untreated
      psychosis (DUP) and arrest early deterioration may have long-term benefits. AIMS:
      To test the critical period hypothesis by determining whether outcome in non
      affective psychosis stabilises beyond the critical period and whether DUP
      correlates with 8-year outcome; to determine whether duration of untreated
      illness (DUI) has any independent effect on outcome. METHOD: We recruited 118
      people consecutively referred with first-episode psychosis to a prospective,
      naturalistic cohort study. RESULTS: Negative and disorganised symptoms improved
      between 4 and 8 years. Duration of untreated psychosis predicted remission,
      positive symptoms and social functioning at 8 years. Continuing functional
      recovery between 4 and 8 years was predicted by DUI. CONCLUSIONS: These results
      provide qualified support for the critical period hypothesis. The critical period
      could be extended to include the prodrome as well as early psychosis.

PMID- 19118321
TI  - Neural correlates of executive function and working memory in the 'at-risk mental
      state'.
AB  - BACKGROUND: People with prodromal symptoms have a very high risk of developing
      psychosis. AIMS: To use functional magnetic resonance imaging to examine the
      neurocognitive basis of this vulnerability. METHOD: Cross-sectional comparison of
      regional activation in individuals with an'at-risk mental state' (at-risk group:
      n=17), patients with first-episode schizophreniform psychosis (psychosis group:
      n=10) and healthy volunteers (controls: n=15) during an overt verbal fluency task
      and an N-back working memory task. RESULTS: A similar pattern of between-group
      differences in activation was evident across both tasks. Activation in the at
      risk group was intermediate relative to that in controls and the psychosis group
      in the inferior frontal and anterior cingulate cortex during the verbal fluency
      task and in the inferior frontal, dorsolateral prefrontal and parietal cortex
      during the N-back task. CONCLUSIONS: The at-risk mental state is associated with
      abnormalities of regional brain function that are qualitatively similar to, but
      less severe than, those in patients who have recently presented with psychosis.

PMID- 19118323
TI  - Diagnostic accuracy of 123I-FP-CIT SPECT in possible dementia with Lewy bodies.
AB  - BACKGROUND: (123)I-FP-CIT SPECT (single photon emission computed tomography) can
      help in the differential diagnosis of probable dementia with Lewy bodies (Lewy
      body dementia) and Alzheimer's disease. AIMS: Our aim was to determine the
      accuracy of (123)I-FP-CIT SPECT in diagnosing people with possible dementia with
      Lewy bodies. METHOD: We undertook a 12-month follow-up of 325 individuals with
      probable or possible Lewy body or non-Lewy body dementia who had previously
      undergone (123)I-FP-CIT SPECT. A consensus panel, masked to SPECT findings,
      established diagnosis at 12 months in 264 people. RESULTS: Of 44 people with
      possible dementia with Lewy bodies at baseline, at follow-up the diagnosis for 19
      people was probable dementia with Lewy bodies (43%), in 7 people non-Lewy body
      dementia (16%) and for 18 individuals it remained possible dementia with Lewy
      bodies (41%). Of the 19 who at follow-up were diagnosed with probable dementia
      with Lewy bodies, 12 had abnormal scans at baseline (sensitivity 63%); all 7
      individuals with a possible diagnosis who were diagnosed as having Alzheimer's
      disease at follow-up had normal scans (specificity 100%). CONCLUSIONS: Our
      findings confirm the diagnostic accuracy of (123)I-FP-CIT SPECT in distinguishing
      Lewy body from non-Lewy body dementia and also suggest a clinically useful role
      in diagnostically uncertain cases, as an abnormal scan in a person with possible
      dementia with Lewy bodies is strongly suggestive of dementia with Lewy bodies.

PMID- 19118324
TI  - Aripiprazole monotherapy in acute mania: 12-week randomised placebo- and
      haloperidol-controlled study.
AB  - BACKGROUND: Well-tolerated and effective therapies for bipolar mania are
      required. AIMS: To evaluate the efficacy and tolerability of aripiprazole as
      acute and maintenance of effect therapy in patients with bipolar I disorder
      experiencing manic or mixed episodes. METHOD: Patients were randomised to double
      blind aripiprazole (15 or 30 mg/day; n=167), placebo (n=153) or haloperidol (5-15
      mg/day, n=165) for 3 weeks (trial registration NCT00097266). Aripiprazole- and
      haloperidol-treated patients remained on masked treatment for 9 additional weeks.
      RESULTS: Mean change in Young Mania Rating Scale Total score (primary end-point)
      at week 3 was significantly greater with aripiprazole (-12.0; P<0.05) and
      haloperidol (-12.8; P<0.01) than with placebo (-9.7). Improvements were
      maintained to week 12 for aripiprazole (-17.2) and haloperidol (-17.8).
      Aripiprazole was well tolerated. Extrapyramidal adverse events were more frequent
      with haloperidol than aripiprazole (53.3% v. 23.5%). CONCLUSIONS: Clinical
      improvements with aripiprazole were sustained to week 12. Aripiprazole was
      generally well tolerated.

PMID- 19118325
TI  - Patients' views and readmissions 1 year after involuntary hospitalisation.
AB  - BACKGROUND: Little is known about the long-term outcome of involuntary admissions
      to psychiatric hospitals. AIMS: To assess involuntary readmissions and patients'
      retrospective views of the justification of the admission as 1-year outcomes and
      to identify factors associated with these outcomes. METHOD: Socio-demographic
      data and readmissions were collected for 1570 involuntarily admitted patients.
      Within the first week after admission 50% were interviewed, and of these 51% were
      re-interviewed after 1 year. RESULTS: At 1 year, 15% of patients had been
      readmitted involuntarily, and 40% considered their original admission justified.
      Lower initial treatment satisfaction, being on benefits, living with others and
      being of African and/or Caribbean origin were associated with higher involuntary
      readmission rates. Higher initial treatment satisfaction, poorer initial global
      functioning and living alone were linked with more positive retrospective views
      of the admission. CONCLUSIONS: Patients' views of treatment within the first week
      are a relevant indicator for the long-term prognosis of involuntarily admitted
      patients.

PMID- 19118326
TI  - Developing a care pathway for advance decisions and powers of attorney:
      qualitative study.
AB  - BACKGROUND: The Mental Capacity Act for England and Wales empowers individuals to
      plan ahead for when they may lack capacity. AIMS: To develop a care pathway for
      advance decisions and powers of attorney using Huntington's disease as an
      exemplar. METHOD: Qualitative study using in-depth individual interviews with
      service users and carers, and focus groups with professionals. Inductive
      qualitative analysis was used to develop themes to construct a care pathway that
      was then piloted and further evaluated to achieve a final pathway. RESULTS: A
      care pathway was developed that incorporated an early introduction through a
      formal education session and a minimum of two sessions separated by at least 2
      weeks before advance decision completion. Optimal delivery of this intervention
      requires significant clinical and administrative commitment. CONCLUSIONS: We have
      developed a simple, easy-to-follow care pathway that was acceptable to users and
      providers.

PMID- 19118328
TI  - Psychopathy traits in adolescents with childhood attention-deficit hyperactivity
      disorder.
AB  - BACKGROUND: Children with attention-deficit hyperactivity disorder (ADHD) are
      thought to be at higher risk of psychopathy. Early biological and social
      adversity may contribute to this risk. AIMS: To examine psychopathy traits in
      ADHD. METHOD: In a sample of children with ADHD who had reached adolescence,
      total psychopathy and 'emotional-dysfunction' scores (e.g. callousness, lack of
      affect) were assessed using the Hare Psychopathy Checklist-Youth Version.
      RESULTS: A total of 156 (79%) eligible families participated. Total psychopathy
      and emotional-dysfunction scores were elevated in comparison to published UK
      norms but none scored in the clinical range for psychopathy. Adjusting for
      associated conduct problems, total psychopathy scores were associated with
      maternal smoking during pregnancy, emotional-dysfunction scores were associated
      with birth complications, and neither was associated with family adversity.
      CONCLUSIONS: Children with ADHD show psychopathy traits but are not
      'psychopaths'. Early adversity, indexed by pre- or perinatal adversity but not
      family factors, appears to be associated.

PMID- 19118330
TI  - Self-harm in adolescents: self-report survey in schools in Scotland.
AB  - BACKGROUND: The suicide rate in Scotland is twice as high as that in England.
      However, the prevalence of self-harm is unknown. AIMS: To determine the
      prevalence of self-harm in adolescents in Scotland and the factors associated
      with it. METHOD: A total of 2008 pupils aged 15-16 years completed an anonymous
      lifestyle and coping survey. Information was obtained on demographic
      characteristics, lifestyle, life events and problems, social influences,
      psychological variables and self-harm. RESULTS: Self-harm was reported by 13.8%
      of the respondents. The majority (71%) of those who had self-harmed had done so
      in the past 12 months and girls were approximately 3.4 times more likely to
      report self-harm than boys. In multivariate analyses, smoking, bullying, worries
      about sexual orientation, self-harm by family and anxiety were associated with
      self-harm in both genders. In addition, drug use, physical abuse, serious
      boy/girlfriend problems, self-harm by friends and low levels of optimism were
      also associated with self-harm in girls. CONCLUSIONS: Despite markedly different
      national suicide rates, the prevalence of self-harm in Scotland is similar to
      that in England with girls at least three times more likely to report self-harm
      than boys. The findings suggest a role for emotional literacy programmes in
      schools and highlight the importance of promoting positive mental health among
      adolescents.

PMID- 19118331
TI  - Repetition of acute poisoning in Oslo: 1-year prospective study.
AB  - BACKGROUND: The repetition of acute poisoning occurs frequently. The intention
      may change between episodes and many poisonings are treated outside the hospital
      setting. Few studies have taken this into account. AIMS: To quantify the
      repetition frequency regardless of the level of health care or the intention
      behind the poisoning, and to identify possible risk factors for repetition.
      METHOD: A prospective multicentre study of all acute poisonings in Oslo treated
      in hospital, at an out-patient clinic or by the ambulance service. Repetition was
      estimated using Kaplan-Meier calculations, and predictive factors were identified
      using Cox regression analysis. RESULTS: The estimated 1-year repetition rate was
      30% (95% CI 24-35). Independent predictors of repetition were middle age (30-49
      years), poisoning with opiates or sedatives, unemployment or living on social
      welfare, a previous suicide attempt, and a history of psychiatric treatment.
      Intention was not a significant predictor. CONCLUSIONS: Repetition of acute
      poisoning is high, irrespective of the level of healthcare and the intention
      behind the poisoning.

PMID- 19118332
TI  - Effect of 7 July 2005 terrorist attacks in London on suicide in England and
      Wales.
AB  - BACKGROUND: A reduction in suicide in England and Wales has been reported after
      the attacks of 11 September 2001 in the USA. It may be plausible therefore to
      expect a much greater impact on suicide in the UK in response to the events of 7
      July 2005, caused by the first suicide terrorist attack by Islamic extremists on
      British soil. AIMS: To examine the effect of the 7 July 2005 terrorist attacks in
      London on suicide rates in England and Wales. METHOD: Analysis of number of
      suicide (ICD-10 codes X60-X84) and undetermined injury deaths (ICD-10 codes Y10
      Y34) reported in England and Wales in the 12 weeks before and after 7 July 2005.
      We used Shewhart Control Charts based on Poisson rates to explore adjusted daily
      and weekly suicide rates and rate differences with respect to 7 July 2005.
      RESULTS: A brief but significant reduction in daily suicide rate was observed a
      few days after the terrorist attack in London on 7 July 2005. Further reduction
      was also observed on the 21 July 2005, coinciding with the second wave of
      attacks. No similar reduction in suicide was seen during the same period in the
      previous 4 years. Poisson regression models with indicator variables for each day
      in July 2005 revealed a reduction of 40% of the expected daily rate for these 2
      days only. We found no evidence of any longer-term effect on suicide.
      CONCLUSIONS: The study findings are contrary to our expectation and only weakly
      support Durkheim's theory that periods of national threat lower the suicide rate
      through the impact on social cohesion. It is possible that previous experience of
      IRA terrorism in the UK may have limited the effect of the 7 July 2005 attacks on
      suicide in England and Wales. The shock value of suicide terrorism and its
      psychological potency appear to diminish over time as the tactic becomes
      overused.

PMID- 19118334
TI  - Family participation in treatment, post-discharge appointment and medication
      adherence at a Nigerian psychiatric hospital.
AB  - In low-income countries, clinicians must seek strategies to improve treatment
      adherence that are non-resource intensive and easily integrated into existing
      treatment structures. We conducted a prospective observational cohort study to
      investigate the relationship of family engagement in treatment during
      hospitalisation with post-discharge appointment and medication adherence in 81
      patients from a Nigerian psychiatric hospital. After controlling for gender,
      diagnosis, mental state at discharge, and marital status, family involvement was
      significantly associated with appointment (P=0.047) but not medication adherence
      (P=0.590). Studies are needed to determine whether interventions based on
      engaging families in treatment can improve post-discharge adherence in this
      setting.

PMID- 19118335
TI  - One ace and three faults don't win the set.

PMID- 19118336
TI  - Prisoners with mental disorders in Europe.

PMID- 19118337
TI  - Aetiological significance of middle-ear disease in schizophrenia.

PMID- 19118339
TI  - DSM-V: should PTSD be in a class of its own?

PMID- 19118340
TI  - A pivotal role for the response regulator DegU in controlling multicellular
      behaviour.
AB  - Bacteria control multicellular behavioural responses, including biofilm formation
      and swarming motility, by integrating environmental cues through a complex
      regulatory network. Heterogeneous gene expression within an otherwise isogenic
      cell population that allows for differentiation of cell fate is an intriguing
      phenomenon that adds to the complexity of multicellular behaviour. This review
      focuses on recent data about how DegU, a pleiotropic response regulator, co
      ordinates multicellular behaviour in Bacillus subtilis. We review studies that
      challenge the conventional understanding of the molecular mechanisms underpinning
      the DegU regulatory system and others that describe novel targets of DegU during
      activation of biofilm formation by B. subtilis. We also discuss a novel role for
      DegU in regulating multicellular processes in the food-borne pathogen Listeria
      monocytogenes.

PMID- 19118341
TI  - Early molecular-recognition events in the synthesis and export of group 2
      capsular polysaccharides.
AB  - The outer membrane (OM) of almost all Gram-negative bacteria is composed of
      phospholipids, lipopolysaccharide, proteins and capsular or loosely adherent
      polysaccharides that together mediate cellular interactions with diverse
      environments. Most OM components are synthesized intracellularly or at the inner
      membrane (IM) and thus require an export mechanism. This mini-review focuses on
      recent progress in understanding how synthesis of one kind of capsular
      polysaccharide (group 2) is coupled to the export apparatus located in the IM and
      spanning the periplasmic space, thus providing a transport channel to the cell
      surface. Although the model system for these investigations is the medically
      important extraintestinal pathogen Escherichia coli K1 and its polysialic acid
      capsule, the conclusions are general for other group 2 and group 2-like
      polysaccharides synthesized by many different bacterial species.

PMID- 19118342
TI  - Pathway for H2O2 and O2 detoxification in Clostridium acetobutylicum.
AB  - An unusual non-haem diiron protein, reverse rubrerythrin (revRbr), is known to be
      massively upregulated in response to oxidative stress in the strictly anaerobic
      bacterium Clostridium acetobutylicum. In the present study both in vivo and in
      vitro results demonstrate an H2O2 and O2 detoxification pathway in C.
      acetobutylicum involving revRbr, rubredoxin (Rd) and NADH : rubredoxin
      oxidoreductase (NROR). RevRbr exhibited both NADH peroxidase (NADH : H2O2
      oxidoreductase) and NADH oxidase (NADH : O2 oxidoreductase) activities in in
      vitro assays using NROR as the electron-transfer intermediary from NADH to
      revRbr. Rd increased the NADH consumption rate by serving as an intermediary
      electron-transfer shuttle between NROR and revRbr. While H2O2 was found to be the
      preferred substrate for revRbr, its relative oxidase activity was found to be
      significantly higher than that reported for other Rbrs. A revRbr-overexpressing
      strain of C. acetobutylicum showed significantly increased tolerance to H2O2 and
      O2 exposure. RevRbr thus appears to protect C. acetobutylicum against oxidative
      stress by functioning as the terminal component of an NADH peroxidase and NADH
      oxidase.

PMID- 19118343
TI  - Role of calcium in acclimation of the cyanobacterium Synechococcus elongatus PCC
      7942 to nitrogen starvation.
AB  - A Ca2+ signal is required for the process of heterocyst differentiation in the
      filamentous diazotrophic cyanobacterium Anabaena sp. PCC 7120. This paper
      presents evidence that a transient increase in intracellular free Ca2+ is also
      involved in acclimation to nitrogen starvation in the unicellular non
      diazotrophic cyanobacterium Synechococcus elongatus PCC 7942. The Ca2+ transient
      was triggered in response to nitrogen step-down or the addition of 2-oxoglutarate
      (2-OG), or its analogues 2,2-difluoropentanedioic acid (DFPA) and 2
      methylenepentanedioic acid (2-MPA), to cells growing with combined nitrogen,
      suggesting that an increase in intracellular 2-OG levels precedes the Ca2+
      transient. The signalling protein P(II) and the transcriptional regulator NtcA
      appear to be needed to trigger the signal. Suppression of the Ca2+ transient by
      the intracellular Ca2+ chelator N,N'-[1,2-ethanediylbis(oxy-2,1-phenylene)]bis[N
      [2-[(acetyloxy)methoxy]-2-oxoethyl]]-,bis[(acetyloxy)methyl] ester (BAPTA-AM)
      inhibited expression of the glnB and glnN genes, which are involved in
      acclimation to nitrogen starvation and transcriptionally activated by NtcA. BAPTA
      AM treatment partially inhibited expression of the nblA gene, which is involved
      in phycobiliprotein degradation following nutrient starvation and is regulated by
      NtcA and NblR; in close agreement, BAPTA-AM treatment partially inhibited
      bleaching following nitrogen starvation. Taken together, the results presented
      here strongly suggest an involvement of a defined Ca2+ transient in acclimation
      of S. elongatus to nitrogen starvation through NtcA-dependent regulation.

PMID- 19118344
TI  - Disruption of the epithelial barrier by botulinum haemagglutinin (HA) proteins -
      differences in cell tropism and the mechanism of action between HA proteins of
      types A or B, and HA proteins of type C.
AB  - Orally ingested botulinum neurotoxin (BoNT) causes food-borne botulism, but BoNT
      must pass through the gut lining and enter the bloodstream. We have previously
      found that type B haemagglutinin (HA) proteins in the toxin complex play an
      important role in the intestinal absorption of BoNT by disrupting the
      paracellular barrier of the intestinal epithelium, and therefore facilitating the
      transepithelial delivery of BoNT. Here, we show that type A HA proteins in the
      toxin complex have a similar disruptive activity and a greater potency than type
      B HA proteins in the human intestinal epithelial cell lines Caco-2 and T84 and in
      the canine kidney epithelial cell line MDCK I. In contrast, type C HA proteins in
      the toxin complex (up to 300 nM) have no detectable effect on the paracellular
      barrier in these human cell lines, but do show a barrier-disrupting activity and
      potent cytotoxicity in MDCK I. These findings may indicate that type A and B HA
      proteins contribute to the development of food-borne botulism, at least in
      humans, by facilitating the intestinal transepithelial delivery of BoNTs, and
      that the relative inability of type C HA proteins to disrupt the paracellular
      barrier of the human intestinal epithelium is one of the reasons for the relative
      absence of food-borne human botulism caused by type C BoNT.

PMID- 19118346
TI  - Differential metabolic activity by dental plaque bacteria in association with two
      preparations of MUC5B mucins in solution and in biofilms.
AB  - Salivary mucin, MUC5B, is an oligomeric glycoprotein, heterogeneous in size and
      with a diverse repertoire of oligosaccharides, which differ in composition and
      charge. Since complex salivary glycoproteins are considered to be the major
      source of nutrients for the oral supragingival microbiota, the major aim of the
      current study was to determine whether different preparations of non-denatured
      MUC5B could be isolated exhibiting different biological properties in relation to
      the microflora associated with the surfaces of the oral cavity. Two preparations,
      solMUC5B and gelMUC5B, were isolated by density-gradient centrifugation and were
      shown to have different buoyant densities, carbohydrate content and surface
      adsorbing characteristics. To ascertain differences in biological activity, the
      two mucin preparations, both in solution and adsorbed to a model surface, were
      incubated with freshly isolated dental plaque and assayed for metabolic
      (dehydrogenase) activity with the fluoresecent substrate CTC (5-cyano-2,3-ditolyl
      tetrazolium chloride). The plaque bacteria exhibited higher metabolism with the
      solMUC5B preparation in solution, with 79.4 % active plaque cells compared to the
      controls without mucin (9.6 %), while gelMUC5B showed 48.2 % active cells with
      the same plaque population. In contrast, the same mucins adhered to a surface
      elicited a significantly lower metabolic response, with surface-associated plaque
      cells showing only 12.1 % active cells with solMUC5B and 29.2 % with gelMUC5B.
      These results suggested that the metabolism by the plaque cells adsorbed to
      surface-associated mucins was downregulated compared to the same cells suspended
      in mucin solution. This was confirmed in an experiment where active dispersed
      plaque/solMUC5B suspensions were shown to lose significant metabolic activity
      (e.g. 74.9 to 19.3 %) when allowed to interact with gelMUC5B adsorbed to a
      surface. Clearly, the solMUC5B and gelMUC5B preparations exhibited different
      biological activity when assayed with freshly plaque bacteria in suspension and
      in a biofilm.

PMID- 19118345
TI  - Biofilm formation by group A Streptococcus: a role for the streptococcal
      regulator of virulence (Srv) and streptococcal cysteine protease (SpeB).
AB  - Recently, biofilms have become a topic of interest in the study of the human
      pathogen group A Streptococcus (GAS). In this study, we sought to learn more
      about the make-up of these structures and gain insight into biofilm regulation.
      Enzymic studies indicated that biofilm formation by GAS strain MGAS5005 required
      an extracellular protein and DNA component(s). Previous results indicated that
      inactivation of the transcriptional regulator Srv in MGAS5005 resulted in a
      significant decrease in virulence. Here, inactivation of Srv also resulted in a
      significant decrease in biofilm formation under both static and flow conditions.
      Given that production of the extracellular cysteine protease SpeB is increased in
      the srv mutant, we tested the hypothesis that increased levels of active SpeB may
      be responsible for the reduction in biofilm formation. Western immunoblot
      analysis indicated that SpeB was absent from MGAS5005 biofilms. Complementation
      of MGAS5005Deltasrv restored the biofilm phenotype and eliminated the
      overproduction of active SpeB. Inhibition of SpeB with E64 also restored the
      MGAS5005Deltasrv biofilm to wild-type levels.

PMID- 19118347
TI  - A phenotypic microarray analysis of a Streptococcus mutans liaS mutant.
AB  - Streptococcus mutans, a biofilm-forming Gram-positive bacterium that resides in
      the human oral cavity, is considered to be the primary aetiological agent of
      human dental caries. A cell-envelope stress-sensing histidine kinase, LiaS, is
      considered to be important for expression of virulence factors such as glucan
      binding protein C and mutacin production. In this study, a liaS mutant was
      subjected to phenotypic microarray (PM) analysis of about 2000 phenotypes,
      including utilization of various carbon, nitrogen, phosphate and sulfur sources;
      osmolytes; metabolic inhibitors; and susceptibility to toxic compounds, including
      several types of antibiotics. Compared to the parental strain UA159, the liaS
      mutant strain (IBS148) was more tolerant to various inhibitors that target
      protein synthesis, DNA synthesis and cell-wall biosynthesis. Some of the key
      findings of the PM analysis were confirmed in independent growth studies and by
      using antibiotic discs and E-test strips for susceptibility testing.

PMID- 19118348
TI  - Characterization of an NADH oxidase of the flavin-dependent disulfide reductase
      family from Methanocaldococcus jannaschii.
AB  - Methanocaldococcus jannaschii, a deeply rooted hyperthermophilic anaerobic
      methanarchaeon from a deep-sea hydrothermal vent, carries an NADH oxidase (Nox)
      homologue (MJ0649). According to the characteristics described here, MJ0649
      represents an unusual member within group 3 of the flavin-dependent disulfide
      reductase (FDR) family. This FDR group comprises Nox, NADH peroxidases (Npx) and
      coenzyme A disulfide reductases (CoADRs); each carries a Cys residue that forms
      Cys-sulfenic acid during catalysis. A sequence analysis identified MJ0649 as a
      CoADR homologue. However, recombinant MJ0649 (rMJNox), expressed in Escherichia
      coli and purified to homogeneity an 86 kDa homodimer with 0.27 mol FAD (mol
      subunit)(-1), showed Nox but not CoADR activity. Incubation with FAD increased
      FAD content to 1 mol (mol subunit)(-1) and improved NADH oxidase activity 3.4
      fold. The FAD-incubated enzyme was characterized further. The optimum pH and
      temperature were > or =10 and > or =95 degrees C, respectively. At pH 7 and 83
      degrees C, apparent Km values for NADH and O2 were 3 microM and 1.9 mM,
      respectively, and the specific activity at 1.4 mM O2 was 60 micromol min(-1) mg(
      1); 62 % of NADH-derived reducing equivalents were recovered as H2O2 and the rest
      probably generated H2O. rMjNox had poor NADPH oxidase, NADH peroxidase and
      superoxide formation activities. It reduced ferricyanide, plumbagin and 5,5'
      dithiobis(2-nitrobenzoic acid), but not disulfide coenzyme A and disulfide
      coenzyme M. Due to a high Km, O2 is not a physiologically relevant substrate for
      MJ0649; its true substrate remains unknown.

PMID- 19118349
TI  - Metabolite and transcriptome analysis of Campylobacter jejuni in vitro growth
      reveals a stationary-phase physiological switch.
AB  - Campylobacter jejuni is a prevalent cause of food-borne diarrhoeal illness in
      humans. Understanding of the physiological and metabolic capabilities of the
      organism is limited. We report a detailed analysis of the C. jejuni growth cycle
      in batch culture. Combined transcriptomic, phenotypic and metabolic analysis
      demonstrates a highly dynamic 'stationary phase', characterized by a peak in
      motility, numerous gene expression changes and substrate switching, despite
      transcript changes that indicate a metabolic downshift upon the onset of
      stationary phase. Video tracking of bacterial motility identifies peak activity
      during stationary phase. Amino acid analysis of culture supernatants shows a
      preferential order of amino acid utilization. Proton NMR (1H-NMR) highlights an
      acetate switch mechanism whereby bacteria change from acetate excretion to
      acetate uptake, most probably in response to depletion of other substrates.
      Acetate production requires pta (Cj0688) and ackA (Cj0689), although the acs
      homologue (Cj1537c) is not required. Insertion mutants in Cj0688 and Cj0689
      maintain viability less well during the stationary and decline phases of the
      growth cycle than wild-type C. jejuni, suggesting that these genes, and the
      acetate pathway, are important for survival.

PMID- 19118350
TI  - Involvement of the oscA gene in the sulphur starvation response and in Cr(VI)
      resistance in Pseudomonas corrugata 28.
AB  - Pseudomonas corrugata 28 is a Cr(VI)-hyper-resistant bacterium. A Cr(VI)
      sensitive mutant was obtained by insertional mutagenesis using EZ-Tn5
      <R6Kgammaori/KAN-2>Tnp. The mutant strain was impaired in a gene, here named oscA
      (organosulphur compounds), which encoded a hypothetical small protein of unknown
      function. The gene was located upstream of a gene cluster that encodes the
      components of the sulphate ABC transporter, and it formed a transcriptional unit
      with sbp, which encoded the periplasmic binding protein of the transporter. The
      oscA-sbp transcriptional unit was strongly and quickly overexpressed after
      chromate exposure, suggesting the involvement of oscA in chromate resistance,
      which was further confirmed by means of a complementation experiment. Phenotype
      MicroArray (PM) analysis made it possible to assay 1536 phenotypes and also
      indicated that the oscA gene was involved in the utilization of organosulphur
      compounds as a sole source of sulphur. This is believed to be the first evidence
      that oscA plays a role in activating a sulphur starvation response, which is
      required to cope with oxidative stress induced by chromate.

PMID- 19118351
TI  - Role of the sRNA GcvB in regulation of cycA in Escherichia coli.
AB  - In Escherichia coli, the gcvB gene encodes a small non-translated RNA that
      regulates several genes involved in transport of amino acids and peptides
      (including sstT, oppA and dppA). Microarray analysis identified cycA as an
      additional regulatory target of GcvB. The cycA gene encodes a permease for the
      transport of glycine, d-alanine, d-serine and d-cycloserine. RT-PCR confirmed
      that GcvB and the Hfq protein negatively regulate cycA mRNA in cells grown in
      Luria-Bertani broth. In addition, deletion of the gcvB gene resulted in increased
      sensitivity to d-cycloserine, consistent with increased expression of cycA. A
      cycA : : lacZ translational fusion confirmed that GcvB negatively regulates cycA
      expression in Luria-Bertani broth and that Hfq is required for the GcvB effect.
      GcvB had no effect on cycA : : lacZ expression in glucose minimal medium
      supplemented with glycine. However, Hfq still negatively regulated the fusion in
      the absence of GcvB. A set of transcriptional fusions of cycA to lacZ identified
      a sequence in cycA necessary for regulation by GcvB. Analysis of GcvB identified
      a region complementary to this region of cycA mRNA. However, mutations predicted
      to disrupt base-pairing between cycA mRNA and GcvB did not alter expression of
      cycA : : lacZ. A model for GcvB function in cell physiology is discussed.

PMID- 19118352
TI  - Role of the Escherichia coli Hfq protein in GcvB regulation of oppA and dppA
      mRNAs.
AB  - The gcvB gene encodes a small non-translated RNA (referred to as GcvB) that
      regulates oppA and dppA, two genes that encode periplasmic binding proteins for
      the oligopeptide and dipeptide transport systems. Hfq, an RNA chaperone protein,
      binds many small RNAs and is required for the small RNAs to regulate expression
      of their respective target genes. We showed that repression by GcvB of dppA : :
      lacZ and oppA : : phoA translational fusions is dependent upon Hfq. Double
      mutations in gcvB and hfq yielded similar expression levels of dppA : : lacZ and
      oppA : : phoA compared with gcvB or hfq single mutations, suggesting that GcvB
      and Hfq repress by the same mechanism. The effect of Hfq is not through
      regulation of transcription of gcvB. Hfq is known to increase the stability of
      some small RNAs and to facilitate the interactions between small RNAs and
      specific mRNAs. In the absence of Hfq, there is a marked decrease in the half
      life of GcvB in cells grown in both Luria-Bertani broth and glucose minimal
      medium with glycine, suggesting that part of the role of Hfq is to stabilize
      GcvB. Overproduction of GcvB in wild-type Escherichia coli results in
      superrepression of a dppA : : lacZ fusion, but overproduction of GcvB in an hfq
      mutant does not result in significant repression of the dppA : : lacZ fusion.
      These results suggest that Hfq also is likely required for GcvB-mRNA pairing.

PMID- 19118353
TI  - Regulation of the PcoI/PcoR quorum-sensing system in Pseudomonas fluorescens 2P24
      by the PhoP/PhoQ two-component system.
AB  - A quorum-sensing locus, pcoI/pcoR, which is involved in the regulation of root
      colonization and plant disease-suppressive ability, was previously identified in
      Pseudomonas fluorescens 2P24. In this study, we performed random mutagenesis
      using mini-Tn5 in order to screen the upstream transcriptional regulators of
      pcoI, a biosynthase gene responsible for the synthesis of N-acylhomoserine
      lactone signal molecules. Two mutants, PM400 and PM410, with elevated pcoI gene
      promoter activity, were identified from approximately 10,000 insertion clones.
      The amino acid sequences of the interrupted genes in these two mutants were
      highly similar to PhoQ, a sensor protein of the two-component regulatory system
      PhoP/PhoQ, which responds to environmental Mg2+ starvation and regulates
      virulence in Salmonella typhimurium and antimicrobial peptide resistance in
      Pseudomonas aeruginosa. The promoter activity of pcoI was also induced under low
      Mg2+ conditions in the 2P24 strain of P. fluorescens. Deletion mutagenesis and
      complementation experiments demonstrated that the transcription of pcoI was
      negatively regulated by the sensor PhoQ but positively regulated by the response
      regulator PhoP. Genetic evidence also indicated that transcription of the outer
      membrane protein gene oprH was induced by Mg2+ starvation through regulation of
      the wild-type PhoP/PhoQ system. Additionally, PhoQ was involved in biofilm
      formation by 2P24 under low-Mg2+ conditions through a PhoP-independent pathway.

PMID- 19118354
TI  - In the absence of Lgt, lipoproteins are shed from Streptococcus uberis
      independently of Lsp.
AB  - The role of lipoprotein diacylglyceryl transferase (Lgt) and lipoprotein signal
      peptidase (Lsp) responsible for processing lipoproteins was investigated in
      Streptococcus uberis, a common cause of bovine mastitis. In the absence of Lgt,
      three lipoproteins [MtuA (SUB0473), Hap (SUB1625) and an extracellular solute
      binding protein (SUB0365)] were detected in extracellular locations. All were
      shown by Edman degradation analysis to be cleaved on the carboxy side of the LXXC
      lipobox. Detection of MtuA, a lipoprotein shown previously to be essential for
      infectivity and virulence, was used as a surrogate lipoprotein marker to locate
      and assess processing of lipoproteins. The absence of Lgt did not prevent
      location of MtuA to the cell membrane, its location in the wild-type strain but,
      in contrast to the situation with wild-type, did result in a widespread location
      of this protein. In the absence of both Lgt and Lsp, MtuA was similarly released
      from the bacterial cell. In such strains, however, the cell-associated MtuA
      represented the full-length gene product, indicating that Lsp was able to cleave
      non-lipidated (lipo)proteins but was not responsible for their release from this
      bacterium.

PMID- 19118355
TI  - hag expression in Bacillus subtilis is both negatively and positively regulated
      by ScoC.
AB  - In Bacillus subtilis, motility and chemotaxis require the expression of hag,
      which encodes flagellin. This gene is transcribed by the sigma(D) form of RNA
      polymerase and is regulated by a group of proteins called transition state
      regulators (TSRs). Our studies show that hag transcription is negatively
      regulated by the transition state regulator ScoC, by binding to its promoter.
      Furthermore, ScoC, indirectly, also positively regulates hag by increasing the
      availability of sigma(D) by downregulating the levels of the anti-sigma(D)-factor
      FlgM. We further show that the positive regulation by ScoC predominates over the
      negative regulation.

PMID- 19118356
TI  - Characterization of the LacI-type transcriptional repressor RbsR controlling
      ribose transport in Corynebacterium glutamicum ATCC 13032.
AB  - The gene products of the rbsRACBD (rbs) operon of C. glutamicum (cg1410-cg1414)
      encode a ribose-specific ATP-binding cassette (ABC) transport system and its
      corresponding regulatory protein (RbsR). Deletion of the structural genes rbsACBD
      prohibited ribose uptake. Deletion of the regulatory gene rbsR resulted in an
      increased mRNA level of the whole operon. Analysis of the promoter region of the
      rbs operon by electrophoretic mobility shift assays identified a catabolite
      responsive element (cre)-like sequence as the RbsR-binding site. Additional RbsR
      binding sites were identified in front of the recently characterized uriR operon
      (uriR-rbsK1-uriT-uriH) and the ribokinase gene rbsK2. In vitro, the repressor
      RbsR bound to its targets in the absence of an effector. A probable negative
      effector of RbsR in vivo is ribose 5-phosphate or a derivative thereof, since in
      a ribokinase (rbsK1 rbsK2) double mutant, no derepression of the rbs operon in
      the presence of ribose was observed. Analysis of the ribose stimulon in the C.
      glutamicum wild-type revealed transcriptional induction of the uriR and rbs
      operons as well as of the rbsK2 gene. The inconsistency between the existence of
      functional RbsR-binding sites upstream of the ribokinase genes, their
      transcriptional induction during growth on ribose, and the missing induction in
      the rbsR mutant suggested the involvement of a second transcriptional regulator.
      Simultaneous deletion of the regulatory genes rbsR and uriR finally demonstrated
      a transcriptional co-control of the rbs and uriR operons and the rbsK2 gene by
      both regulators, RbsR and UriR, which were furthermore shown to recognize the
      same cognate DNA sequences in the operators of their target genes.

PMID- 19118358
TI  - Comparative EST analysis of a Zoophthora radicans isolate derived from Pieris
      brassicae and an isogenic strain adapted to Plutella xylostella.
AB  - Zoophthora radicans is an entomopathogenic fungus with the potential to be used
      as an insect biological control agent. To better understand the mechanisms used
      by Z. radicans to infect different hosts, we generated expressed sequence tag
      (EST) datasets from a Z. radicans strain originally isolated from Pieris
      brassicae, and an isogenic strain passaged through Plutella xylostella. In total,
      1839 ESTs were generated which clustered into 466 contigs and 433 singletons to
      provide a set of 899 unique sequences. Approximately 85 % of the ESTs were
      significantly similar (E< or =e(-03)) to other fungal genes, of which 69.6 %
      encoded proteins with a reported function. Proteins involved in protein synthesis
      and metabolism were encoded by 38.3 % of the ESTs, while 26.3 % encoded proteins
      involved in cell-cycle regulation, DNA synthesis, protein fate, transport, cell
      defence, transcription and RNA synthesis, and 4.9 % encoded proteins associated
      with cellular transport, signal transduction, control of cellular organization
      and cell-wall degradation. Several proteinases, including aspartic proteinases,
      trypsins, trypsin-like serine proteases and metalloproteases, with the potential
      to degrade insect cuticle were expressed by the two isolates.

PMID- 19118357
TI  - The two-component system BfrAB regulates expression of ABC transporters in
      Streptococcus gordonii and Streptococcus sanguinis.
AB  - The putative two-component system BfrAB is involved in Streptococcus gordonii
      biofilm development. Here, we provide evidence that BfrAB regulates the
      expression of bfrCD and bfrEFG, which encode two ATP-binding cassette (ABC)
      transporters, and bfrH, which encodes a CAAX amino-terminal protease family
      protein. BfrC and BfrE are ATP-binding proteins, and BfrD, BfrF and BfrG are
      homologous membrane-spanning polypeptides. Similarly, BfrABss, the BfrAB
      homologous system in Streptococcus sanguinis, controls the expression of two
      bfrCD-homologous operons (bfrCDss and bfrXYss), a bfrH-homologous gene (bfrH1ss)
      and another CAAX amino-terminal protease family protein gene (bfrH2ss).
      Furthermore, we demonstrate that the purified BfrA DNA-binding domain from S.
      gordonii binds to the promoter regions of bfrCD, bfrEFG, bfrH, bfrCDss, bfrXYss
      and bfrH1ss in vitro. Finally, we show that the BfrA DNA-binding domain
      recognizes a conserved DNA motif with a consensus sequence of
      TTTCTTTAGAAATATTTTAGAATT. These data suggest, therefore, that S. gordonii BfrAB
      controls biofilm formation by regulating multiple ABC-transporter systems.

PMID- 19118360
TI  - Attenuated enzootic (pestoides) isolates of Yersinia pestis express active
      aspartase.
AB  - It is established that Yersinia pestis, the causative agent of bubonic plague,
      recently evolved from enteropathogenic Yersinia pseudotuberculosis by undergoing
      chromosomal degeneration while acquiring two unique plasmids that facilitate
      tissue invasion (pPCP) and dissemination by fleabite (pMT). Thereafter, plague
      bacilli spread from central Asia to sylvatic foci throughout the world. These
      epidemic isolates exhibit a broad host range including man as opposed to enzootic
      (pestoides) variants that remain in ancient reservoirs where infection is limited
      to muroid rodents. Cells of Y. pseudotuberculosis are known to express glucose-6
      phosphate dehydrogenase (Zwf) and aspartase (AspA); these activities are not
      detectable in epidemic Y. pestis due to missense mutations (substitution of
      proline for serine at amino position 155 of Zwf and leucine for valine at
      position 363 of AspA). In this study, functional Zwf was found in pestoides
      strains E, F and G but not seven other enzootic isolates; enzymic activity was
      associated with retention of serine at amino acid position 155. Essentially, full
      AspA activity occurred in pestoides isolates where valine (pestoides A, B, C and
      D) or serine (pestoides E, F, G and I) occupied position 363. Reduced activity
      occurred in strains Angola and A16, which contained phenylalanine at this
      position. The kcat but not Km of purified AspA from strain Angola was
      significantly reduced. In this context, aspA of the recently described attenuated
      enzootic microtus biovar encodes active valine at position 363, further
      indicating that functional AspA is a biomarker for avirulence of Y. pestis in
      man.

PMID- 19118361
TI  - Identification of iron-responsive proteins expressed by Chlamydia trachomatis
      reticulate bodies during intracellular growth.
AB  - The obligate intracellular bacterium Chlamydia trachomatis serovar E is the most
      prevalent cause of bacterial sexually transmitted disease. With an established
      requirement for iron, the developmental cycle arrests at the intracellular
      reticulate body stage during iron restriction, resulting in a phenomenon termed
      persistence. Persistence has implications in natural infections for altered
      expression of virulence factors and antigens, in addition to a potential role in
      producing chronic infection. In this study, chlamydial proteins in iron
      restricted, infected HEC-1B cells were radiolabelled during mid-developmental
      cycle growth, harvested, and separated using two-dimensional polyacrylamide gel
      electrophoresis (2D-PAGE). Of approximately 250 radiolabelled protein species
      visualized, densitometric analysis revealed 25 proteins that increased in
      expression under iron restriction compared to iron-sufficient control samples;
      ten protein species identified by mass spectrometry are involved in the oxidative
      damage response (alkyl hydroperoxide reductase, 6-phosphogluconolactonase and
      acyl carrier protein synthase), transcription (RNA polymerase subunit alpha and
      transcription anti-termination factors NusA and NusG), protein modification
      (peptide deformylase and trigger factor), and virulence (Chlamydia protein
      associating with death domains, CADD). Transcript-level expression patterns of
      ahpC, devB, cadd, fabF and ct538 were measured by quantitative RT-PCR throughout
      the developmental cycle, and each gene examined demonstrated a significant but
      small mid-cycle increase in transcript level in iron-restricted cultures compared
      to iron-replete controls. Taken together, these data suggest that the primary
      response of chlamydiae to reduced iron availability is to increase expression of
      proteins involved in protection against oxidative damage via iron-catalysed
      generation of reactive oxygen species and adaptation to stress by increasing
      expression of transcriptional machinery and other stress-responsive proteins.

PMID- 19118359
TI  - Experimental determination of translational start sites resolves uncertainties in
      genomic open reading frame predictions - application to Mycobacterium
      tuberculosis.
AB  - Correct identification of translational start sites is important for
      understanding protein function and transcriptional regulation. The annotated
      translational start sites contained in genome databases are often predicted using
      bioinformatics and are rarely verified experimentally, and so are not all
      accurate. Therefore, we devised a simple approach for determining translational
      start sites using a combination of epitope tagging and frameshift mutagenesis.
      This assay was used to determine the start sites of three Mycobacterium
      tuberculosis proteins: LexA, SigC and Rv1955. We were able to show that proteins
      may begin before or after the predicted site. We also found that a small, non
      annotated open reading frame upstream of Rv1955 was expressed as a protein, which
      we have designated Rv1954A. This approach is readily applicable to any bacterial
      species for which plasmid transformation can be achieved.

PMID- 19118362
TI  - Deletion of tolA in Salmonella Typhimurium generates an attenuated strain with
      vaccine potential.
AB  - The Gram-negative Tol-Pal system of envelope proteins plays a key role in
      maintaining outer membrane integrity and contributes to the virulence of several
      pathogens. We have investigated the role of one of these proteins, TolA, in the
      biology of Salmonella enterica serovar Typhimurium. Deletion of tolA rendered
      strain SL1344 more susceptible to killing by bile and human serum. In addition
      the mutant had impaired membrane integrity and displayed alterations in LPS
      production. The tolA mutant was highly attenuated in mouse infections via the
      oral and intravenous routes. Importantly, each phenotype displayed by the mutant
      was complemented by provision of tolA in trans. The tolA gene therefore
      contributes to virulence, membrane integrity, LPS production and bile and serum
      resistance in S. enterica serovar Typhimurium SL1344. Finally, immunization with
      the tolA mutant provided significant protection against subsequent challenge with
      wild-type SL1344. The Tol-Pal system is therefore a potential target in the
      development of novel attenuated live vaccines against Salmonella and other Gram
      negative pathogens.

PMID- 19118363
TI  - Osmoregulated periplasmic glucans of Salmonella enterica serovar Typhimurium are
      required for optimal virulence in mice.
AB  - We purified osmoregulated periplasmic glucans (OPGs) from Salmonella enterica
      serovar Typhimurium and found them to be composed of 100 % glucose with 2-linked
      glucose as the most abundant residue, with terminal glucose, 2,3-linked and 2,6
      linked glucose also present in high quantities. The two structural genes for OPG
      biosynthesis, opgG and opgH, form a bicistronic operon, and insertion of a
      kanamycin resistance gene cassette into this operon resulted in a strain devoid
      of OPGs. The opgGH mutant strain was impaired in motility and growth under low
      osmolarity conditions. The opgGH mutation also resulted in a 2 log increase in
      the LD50 in mice compared to the wild-type strain SL1344. Inability to synthesize
      OPGs had no significant impact on the organism's lipopolysaccharide pattern or
      its ability to survive antimicrobial peptides-, detergent-, pH- and nutrient
      stress conditions. We observed that the opgGH-defective strain respired at a
      reduced rate under acidic growth conditions (pH 5.0) and had lower ATP levels
      compared to the wild-type strain. These data indicate that OPGs of S. Typhimurium
      contribute towards mouse virulence as well as growth and motility under low
      osmolarity growth conditions.

PMID- 19118364
TI  - SufA - a bacterial enzyme that cleaves fibrinogen and blocks fibrin network
      formation.
AB  - Finegoldia magna is a member of the normal human bacterial flora on the skin and
      other non-sterile body surfaces, but this anaerobic coccus is also an important
      opportunistic pathogen. SufA was the first F. magna proteinase to be isolated and
      characterized. Many bacterial pathogens interfere with different steps of blood
      coagulation, and here we describe how purified SufA efficiently and specifically
      cleaves fibrinogen in human plasma. SufA is both secreted by F. magna and
      associated with the bacterial surface. Successful gene targeting has previously
      not been performed in anaerobic cocci, but in order to study the role of the SufA
      that is present at the bacterial surface, we constructed an F. magna mutant that
      expresses a truncated SufA lacking proteolytic activity. In contrast to wild-type
      bacteria that delayed the coagulation of human plasma, mutant bacteria had no
      such effect. Wild-type and mutant bacteria adhered to keratinocytes equally well,
      but in a plasma environment only wild-type bacteria blocked the formation of
      fibrin networks surrounding adherent bacteria. The effective cleavage of
      fibrinogen by SufA suggests that the interference with fibrin network formation
      represents an adaptive mechanism of F. magna with potential implications also for
      pathogenicity.

PMID- 19118365
TI  - The Na+-translocating NADH : ubiquinone oxidoreductase of Azotobacter vinelandii
      negatively regulates alginate synthesis.
AB  - Azotobacter vinelandii is a nitrogen-fixing soil bacterium that produces the
      exopolysaccharide alginate. In this report we describe the isolation and
      characterization of A. vinelandii strain GG4, which carries an nqrE : : Tn5
      mutation resulting in alginate overproduction. The nqrE gene encodes a subunit of
      the Na+-translocating NADH : ubiquinone oxidoreductase (Na+-NQR). As expected,
      Na+-NQR activity was abolished in mutant GG4. When this strain was complemented
      with the nqrEF genes this activity was restored and alginate production was
      reduced to wild-type levels. Na+-NQR may be the main sodium pump of A. vinelandii
      under the conditions tested ( approximately 2 mM Na+) since no Na+/H+-antiporter
      activity was detected. Collectively our results indicate that in A. vinelandii
      the lack of Na+-NQR activity caused the absence of a transmembrane Na+ gradient
      and an increase in alginate production.

PMID- 19118366
TI  - SMb20651 is another acyl carrier protein from Sinorhizobium meliloti.
AB  - Acyl carrier proteins (ACPs) are small acidic proteins that carry growing acyl
      chains during fatty acid or polyketide synthesis. In rhizobia, there are four
      different and well-characterized ACPs: AcpP, NodF, AcpXL and RkpF. The genome
      sequence of Sinorhizobium meliloti 1021 reveals two additional ORFs that possibly
      encode additional ACPs. One of these, smb20651, is located on the plasmid pSymB
      as part of an operon. The genes of the operon encode a putative asparagine
      synthetase (AsnB), the predicted ACP (SMb20651), a putative long-chain fatty acyl
      CoA ligase (SMb20650) and a putative ammonium-dependent NAD+ synthetase (NadE1).
      When SMb20651 was overexpressed in Escherichia coli, [3H]beta-alanine, a
      biosynthetic building block of 4'-phosphopantetheine, was incorporated into the
      protein in vivo. The purified SMb20651 was modified with 4'-phosphopantetheine in
      the presence of S. meliloti holo-ACP synthase (AcpS). Also, holo-SMb20651 was
      modified in vitro with a malonyl group by malonyl CoA-ACP transacylase. In E.
      coli, coexpression of SMb20651 together with other proteins such as AcpS and
      SMb20650 led to the formation of additional forms of SMb20651. In this bacterium,
      acylation of SMb20651 with C12 : 0 or C18 : 0 fatty acids was detected,
      demonstrating that this protein is involved in fatty acid biosynthesis or
      transfer. Expression of SMb20651 was detected in S. meliloti as holo-SMb20651 and
      acyl-SMb20651.

PMID- 19118367
TI  - In vivo measurement of cytosolic and mitochondrial pH using a pH-sensitive GFP
      derivative in Saccharomyces cerevisiae reveals a relation between intracellular
      pH and growth.
AB  - The specific pH values of cellular compartments affect virtually all biochemical
      processes, including enzyme activity, protein folding and redox state. Accurate,
      sensitive and compartment-specific measurements of intracellular pH (pHi)
      dynamics in living cells are therefore crucial to the understanding of stress
      response and adaptation. We used the pH-sensitive GFP derivative 'ratiometric
      pHluorin' expressed in the cytosol and in the mitochondrial matrix of growing
      Saccharomyces cerevisiae to assess the variation in cytosolic pH (pHcyt) and
      mitochondrial pH (pHmit) in response to nutrient availability, respiratory chain
      activity, shifts in environmental pH and stress induced by addition of sorbic
      acid. The in vivo measurement allowed accurate determination of organelle
      specific pH, determining a constant pHcyt of 7.2 and a constant pHmit of 7.5 in
      cells exponentially growing on glucose. We show that pHcyt and pHmit are
      differentially regulated by carbon source and respiratory chain inhibitors. Upon
      glucose starvation or sorbic acid stress, pHi decrease coincided with growth
      stasis. Additionally, pHi and growth coincided similarly in recovery after
      addition of glucose to glucose-starved cultures or after recovery from a sorbic
      acid pulse. We suggest a relation between pHi and cellular energy generation, and
      therefore a relation between pHi and growth.

PMID- 19118368
TI  - Interaction of the mechanism-based inactivator acetylene with ammonia
      monooxygenase of Nitrosomonas europaea.
AB  - The ammonia monooxygenase (AMO) of Nitrosomonas europaea is a metalloenzyme that
      catalyses the oxidation of ammonia to hydroxylamine. We have identified histidine
      191 of AmoA as the binding site for the oxidized mechanism-based inactivator
      acetylene. Binding of acetylene changed the molecular mass of His-191 from 155.15
      to 197.2 Da (+42.05), providing evidence that acetylene was oxidized to ketene
      (CH2CO; 42.04 Da) which binds specifically to His-191. It must be assumed that
      His-191 is part of the acetylene-activating site in AMO or at least directly
      neighbours this site.

PMID- 19118369
TI  - Mechanism of conjugated linoleic acid and vaccenic acid formation in human faecal
      suspensions and pure cultures of intestinal bacteria.
AB  - Faecal bacteria from four human donors and six species of human intestinal
      bacteria known to metabolize linoleic acid (LA) were incubated with LA in
      deuterium oxide-enriched medium to investigate the mechanisms of conjugated
      linoleic acid (CLA) and vaccenic acid (VA) formation. The main CLA products in
      faecal suspensions, rumenic acid (cis-9,trans-11-CLA; RA) and trans-9,trans-11
      CLA, were labelled at C-13, as were other 9,11 geometric isomers. Traces of trans
      10,cis-12-CLA formed were labelled to a much lower extent. In pure culture,
      Bifidobacterium breve NCFB 2258 formed labelled RA and trans-9,trans-11-CLA,
      while Butyrivibrio fibrisolvens 16.4, Roseburia hominis A2-183T, Roseburia
      inulinivorans A2-192T and Ruminococcus obeum-like strain A2-162 converted LA to
      VA, labelled in a manner indicating that VA was formed via C-13-labelled RA.
      Propionibacterium freudenreichii subsp. shermanii DSM 4902T, a possible
      probiotic, formed mainly RA with smaller amounts of trans-10,cis-12-CLA and trans
      9,trans-11-CLA, labelled the same as in the mixed microbiota. Ricinoleic acid (12
      OH-cis-9-18 : 1) did not form CLA in the mixed microbiota, in contrast to CLA
      formation described for Lactobacillus plantarum. These results were similar to
      those reported for the mixed microbiota of the rumen. Thus, although the
      bacterial genera and species responsible for biohydrogenation in the rumen and
      the human intestine differ, and a second route of RA formation via a 10-OH-18 : 1
      is present in the intestine, the overall labelling patterns of different CLA
      isomers formation are common to both gut ecosystems. A hydrogen-abstraction
      enzymic mechanism is proposed that may explain the role of a 10-OH-18 : 1
      intermediate in 9,11-CLA formation in pure and mixed cultures.

PMID- 19118370
TI  - Oxidative stress and disruption of labile iron generate specific auxotrophic
      requirements in Salmonella enterica.
AB  - The response of a cell to integrated stresses was investigated using
      environmental and/or genetic perturbations that disrupted labile iron homeostasis
      and increased oxidative stress. The effects of the perturbations were monitored
      as nutritional requirements, and were traced to specific enzymic targets. A yggX
      gshA cyaY mutant strain required exogenous thiamine and methionine for growth.
      The thiamine requirement, which had previously been linked to the Fe-S cluster
      proteins ThiH and ThiC, was responsive to oxidative stress and was not directly
      affected by manipulation of the iron pool. The methionine requirement was
      associated with the activity of sulfite reductase, an enzyme that appeared
      responsive to disruption of labile iron homeostasis. The results are incorporated
      in a model to suggest how the activity of iron-containing enzymes not directly
      sensitive to oxygen can be decreased by oxidation of the labile iron pool.

PMID- 19118371
TI  - Citrate-mediated iron uptake in Pseudomonas aeruginosa: involvement of the
      citrate-inducible FecA receptor and the FeoB ferrous iron transporter.
AB  - In an attempt to identify components of a ferric citrate uptake system in
      Pseudomonas aeruginosa, a mutant library of a siderophore-deficient strain
      (IA614) was constructed and screened for defects in citrate-promoted growth in an
      Fe-restricted medium. A mutant disrupted in gene PA3901, encoding a homologue of
      the outer-membrane ferric citrate receptor, FecA, of Escherichia coli
      (FecA(E.c.)), was recovered and shown to be deficient in citrate-promoted growth
      and citrate-mediated Fe uptake. A mutant disrupted in gene PA4825, encoding a
      homologue of the MgtA/MgtB Mg2+ transporters in Salmonella enterica, was
      similarly deficient in citrate-promoted growth, though this was due to a citrate
      sensitivity of the mutant apparently resulting from citrate-promoted acquisition
      of Fe2+ and resultant oxidative stress. Consistent with citrate delivering Fe to
      cells as Fe2+, a P. aeruginosa mutant lacking the FeoB Fe2+ transporter
      homologue, PA4358, was compromised for citrate-promoted growth in Fe-restricted
      medium and showed markedly reduced citrate-mediated Fe uptake. Subsequent
      elimination of two Fe3+ transporter homologues, PA5216 and PA4687, in the feoB
      mutant failed to further compromise citrate-promoted growth or Fe uptake, though
      the additional loss of pcoA, encoding a periplasmic ferroxidase implicated in
      Fe2+ acquisition, completely abrogated citrate-mediated Fe uptake. Fe acquisition
      mediated by other siderophores (e.g. pyoverdine) was, however, unaffected in the
      quadruple knockout strain. These data indicate that Fe delivered to P. aeruginosa
      by citrate is released as Fe2+, probably in the periplasm, prior to its transport
      into cells via Fe transport components.

PMID- 19118372
TI  - Prognostic implications of anemia in older adults.

PMID- 19118373
TI  - Paroxysmal nocturnal hemoglobinuria and myelodysplastic syndromes: clonal
      expansion of PIG-A-mutant hematopoietic cells in bone marrow failure.

PMID- 19118374
TI  - Clinical relevance of JAK2 (V617F) mutant allele burden.

PMID- 19118375
TI  - Treatment of acute myeloid leukemia.

PMID- 19118376
TI  - Clinicobiological, prognostic and therapeutic implications of the tumor
      microenvironment in follicular lymphoma.

PMID- 19118377
TI  - Obituary: Ernest Beutler (1928-2008).

PMID- 19118378
TI  - A low dose of ritonavir-boosted atazanavir provides adequate pharmacokinetic
      parameters in HIV-1-infected Thai adults.
AB  - Several dose-finding studies of boosted protease inhibitors have demonstrated
      that doses lower than those recommended in Caucasian populations exhibit in the
      Thai population similar pharmacokinetic (PK) properties with sustained
      virological suppression but reduced toxicity. We therefore evaluated the PK
      profiles of lower than the standard doses of atazanavir/ritonavir (ATV/RTV) in 22
      adult Thai patients with well-suppressed human immunodeficiency virus 1 (HIV-1)
      infection. The PK parameters of ATV/RTV at a dosage of 200/100 mg once daily,
      plus two nucleoside reverse transcriptase inhibitors, were significantly lower
      than those associated with a dosage of 300/100 mg once daily in the same
      patients. In addition, the PK parameters for the lower dosage in these Thai
      patients were comparable to historical data from Caucasian cohorts who received
      the standard dose of ATV/RTV (300/100 mg). None of the patients showed
      subtherapeutic values of <0.15 mg/l at any time point. Bilirubin concentration
      decreased significantly after dose reduction, and viral load remained at <50
      copies/ml in all subjects. Therefore, ATV/RTV at a dose of 200/100 mg once daily
      (plus appropriate backbone medication) warrants further long-term efficacy
      studies, particularly in patients of Thai and other Asian ethnicities.

PMID- 19118379
TI  - Impact of different low-dose ritonavir regimens on lipids, CD36, and adipophilin
      expression.
AB  - We investigated the relationship between ritonavir concentrations and changes in
      lipids, vascular inflammation markers, CD36, and adipophilin expression in
      volunteers randomly assigned to groups receiving 100 mg of ritonavir once daily
      or twice daily. In both groups decreases in high-density lipoprotein (HDL) (6%, P
      = 0.010; and 10%, P < 0.001, respectively) and CD36 (14%, P = 0.012; and 16%, P =
      0.006, respectively) and increases in the vascular inflammation marker sCD40L
      (12%, P = 0.008; 19%, P = 0.003, respectively) were seen. Increases in
      adipophilin (30%, P = 0.044) and triglycerides (32%, P = 0.044) were seen only in
      the group receiving ritonavir twice daily. The ritonavir concentration in the
      plasma correlated with changes in triglycerides, HDL, and adipophilin (r = 0.34,
      P = 0.030; r = 0.33, P = 0.040; and r = 0.4, P = 0.01, respectively).

PMID- 19118380
TI  - Abacavir pharmacokinetics during chronic therapy in HIV-1-infected adolescents
      and young adults.
AB  - The pharmacokinetics of abacavir and its metabolites were investigated in 30
      human immunodeficiency virus (HIV)-infected adolescents and young adults 13-25
      years of age, equally divided into two groups: <18 years of age and >or=18 years
      of age. All the subjects received the recommended adult dose of 300 mg twice
      daily. The area under the plasma concentration-time curve (AUC) and half-life of
      abacavir did not differ significantly between the age groups or by gender or
      race, and there were only modest associations of age with apparent abacavir
      clearance and with volume of distribution. There were no significant correlations
      of carboxylate or glucuronide metabolite levels with age or gender, although
      glucuronide AUC was higher in Hispanic subjects than in African-American
      subjects. Zidovudine and lamivudine concentration profiles were also similar in
      the two age groups. A novel aspect of the study included an assessment of
      intracellular carbovir, zidovudine, and lamivudine triphosphate levels, and these
      were found to be similar in the two age-based groups. Overall, these findings
      suggest that current recommendations relating to adult dosages are appropriate
      for adolescents and young adults.

PMID- 19118381
TI  - Pyrrolysyl-tRNA synthetase-tRNA(Pyl) structure reveals the molecular basis of
      orthogonality.
AB  - Pyrrolysine (Pyl), the 22nd natural amino acid, is genetically encoded by UAG and
      inserted into proteins by the unique suppressor tRNA(Pyl) (ref. 1). The
      Methanosarcinaceae produce Pyl and express Pyl-containing methyltransferases that
      allow growth on methylamines. Homologous methyltransferases and the Pyl
      biosynthetic and coding machinery are also found in two bacterial species. Pyl
      coding is maintained by pyrrolysyl-tRNA synthetase (PylRS), which catalyses the
      formation of Pyl-tRNA(Pyl) (refs 4, 5). Pyl is not a recent addition to the
      genetic code. PylRS was already present in the last universal common ancestor; it
      then persisted in organisms that utilize methylamines as energy sources. Recent
      protein engineering efforts added non-canonical amino acids to the genetic code.
      This technology relies on the directed evolution of an 'orthogonal' tRNA
      synthetase-tRNA pair in which an engineered aminoacyl-tRNA synthetase (aaRS)
      specifically and exclusively acylates the orthogonal tRNA with a non-canonical
      amino acid. For Pyl the natural evolutionary process developed such a system some
      3 billion years ago. When transformed into Escherichia coli, Methanosarcina
      barkeri PylRS and tRNA(Pyl) function as an orthogonal pair in vivo. Here we show
      that Desulfitobacterium hafniense PylRS-tRNA(Pyl) is an orthogonal pair in vitro
      and in vivo, and present the crystal structure of this orthogonal pair. The
      ancient emergence of PylRS-tRNA(Pyl) allowed the evolution of unique structural
      features in both the protein and the tRNA. These structural elements manifest an
      intricate, specialized aaRS-tRNA interaction surface that is highly distinct from
      those observed in any other known aaRS-tRNA complex; it is this general property
      that underlies the molecular basis of orthogonality.

PMID- 19118382
TI  - Photon capture and signalling by melanopsin retinal ganglion cells.
AB  - A subset of retinal ganglion cells has recently been discovered to be
      intrinsically photosensitive, with melanopsin as the pigment. These cells project
      primarily to brain centres for non-image-forming visual functions such as the
      pupillary light reflex and circadian photoentrainment. How well they signal
      intrinsic light absorption to drive behaviour remains unclear. Here we report
      fundamental parameters governing their intrinsic light responses and associated
      spike generation. The membrane density of melanopsin is 10(4)-fold lower than
      that of rod and cone pigments, resulting in a very low photon catch and a
      phototransducing role only in relatively bright light. Nonetheless, each captured
      photon elicits a large and extraordinarily prolonged response, with a unique
      shape among known photoreceptors. Notably, like rods, these cells are capable of
      signalling single-photon absorption. A flash causing a few hundred isomerized
      melanopsin molecules in a retina is sufficient for reaching threshold for the
      pupillary light reflex.

PMID- 19118383
TI  - Casein kinase 1alpha governs antigen-receptor-induced NF-kappaB activation and
      human lymphoma cell survival.
AB  - The transcription factor NF-kappaB is required for lymphocyte activation and
      proliferation as well as the survival of certain lymphoma types. Antigen receptor
      stimulation assembles an NF-kappaB activating platform containing the scaffold
      protein CARMA1 (also called CARD11), the adaptor BCL10 and the paracaspase MALT1
      (the CBM complex), linked to the inhibitor of NF-kappaB kinase complex, but
      signal transduction is not fully understood. We conducted parallel screens
      involving a mass spectrometry analysis of CARMA1 binding partners and an RNA
      interference screen for growth inhibition of the CBM-dependent 'activated B-cell
      like' (ABC) subtype of diffuse large B-cell lymphoma (DLBCL). Here we report that
      both screens identified casein kinase 1alpha (CK1alpha) as a bifunctional
      regulator of NF-kappaB. CK1alpha dynamically associates with the CBM complex on T
      cell-receptor (TCR) engagement to participate in cytokine production and
      lymphocyte proliferation. However, CK1alpha kinase activity has a contrasting
      role by subsequently promoting the phosphorylation and inactivation of CARMA1.
      CK1alpha has thus a dual 'gating' function which first promotes and then
      terminates receptor-induced NF-kappaB. ABC DLBCL cells required CK1alpha for
      constitutive NF-kappaB activity, indicating that CK1alpha functions as a
      conditionally essential malignancy gene-a member of a new class of potential
      cancer therapeutic targets.

PMID- 19118384
TI  - The Fas-FADD death domain complex structure unravels signalling by receptor
      clustering.
AB  - The death inducing signalling complex (DISC) formed by Fas receptor, FADD (Fas
      associated death domain protein) and caspase 8 is a pivotal trigger of apoptosis.
      The Fas-FADD DISC represents a receptor platform, which once assembled initiates
      the induction of programmed cell death. A highly oligomeric network of homotypic
      protein interactions comprised of the death domains of Fas and FADD is at the
      centre of DISC formation. Thus, characterizing the mechanistic basis for the Fas
      FADD interaction is crucial for understanding DISC signalling but has remained
      unclear largely because of a lack of structural data. We have successfully formed
      and isolated the human Fas-FADD death domain complex and report the 2.7 A crystal
      structure. The complex shows a tetrameric arrangement of four FADD death domains
      bound to four Fas death domains. We show that an opening of the Fas death domain
      exposes the FADD binding site and simultaneously generates a Fas-Fas bridge. The
      result is a regulatory Fas-FADD complex bridge governed by weak protein-protein
      interactions revealing a model where the complex itself functions as a
      mechanistic switch. This switch prevents accidental DISC assembly, yet allows for
      highly processive DISC formation and clustering upon a sufficient stimulus. In
      addition to depicting a previously unknown mode of death domain interactions,
      these results further uncover a mechanism for receptor signalling solely by
      oligomerization and clustering events.

PMID- 19118385
TI  - Calcium flickers steer cell migration.
AB  - Directional movement is a property common to all cell types during development
      and is critical to tissue remodelling and regeneration after damage. In migrating
      cells, calcium has a multifunctional role in directional sensing, cytoskeleton
      redistribution, traction force generation, and relocation of focal adhesions.
      Here we visualize high-calcium microdomains ('calcium flickers') and their
      patterned activation in migrating human embryonic lung fibroblasts. Calcium
      flicker activity is dually coupled to membrane tension (by means of TRPM7, a
      stretch-activated Ca(2+)-permeant channel of the transient receptor potential
      superfamily) and chemoattractant signal transduction (by means of type 2 inositol
      1,4,5-trisphosphate receptors). Interestingly, calcium flickers are most active
      at the leading lamella of migrating cells, displaying a 4:1 front-to-rear
      polarization opposite to the global calcium gradient. When exposed to a platelet
      derived growth factor gradient perpendicular to cell movement, asymmetric calcium
      flicker activity develops across the lamella and promotes the turning of
      migrating fibroblasts. These findings show how the exquisite spatiotemporal
      organization of calcium microdomains can orchestrate complex cellular processes
      such as cell migration.

PMID- 19118386
TI  - A discrete-time survival analysis of the relationship between truancy and the
      onset of marijuana use.
AB  - OBJECTIVE: Despite truancy being a common behavior among teenagers, little
      research has assessed its deleterious effects. In this study, the effect of
      truancy on the initiation of marijuana use was examined. METHOD: Using data from
      the Rochester Youth Development Study (a longitudinal sample of predominantly
      minority youth), discrete time survival analyses were estimated to assess the
      effect of truancy on the subsequent initiation of marijuana use. The current
      analyses used 5 years of panel data collected from youth and their primary
      caregiver every 6 months throughout adolescence. RESULTS: Truancy was a
      significant predictor of the initiation of marijuana use during each subsequent 6
      month period. The effect was more robust in earlier compared with later
      adolescence. These effects persisted after controlling for potential risk factors
      that are shared by both truancy and drug use, including commitment to school,
      grade-point average, delinquent values, prior involvement in delinquency, peer
      reactions to delinquency, parental monitoring, affective ties to the child, and
      positive parenting. CONCLUSIONS: We argue that the effect is, in part, the result
      of reduced social control (i.e., disengagement from pro-social entities such as
      school) and, in part, the result of the unsupervised, unmonitored time afforded
      by truancy. Prevention initiatives aimed at reducing truancy also may have a
      beneficial impact on preventing the initiation of drug use among adolescents.

PMID- 19118387
TI  - Drinking context and drinking problems among black, white, and Hispanic men and
      women in the 1984, 1995, and 2005 U.S. National Alcohol Surveys.
AB  - OBJECTIVE: The purpose of this study was to investigate the preferred drinking
      contexts of different gender and ethnic groups (white, black, and Hispanic men
      and women), by examining where these groups do most of their drinking and to what
      extent drinking contexts preferences are associated with certain drinking-related
      consequences. METHOD: The study used data from the 1984, 1995, and 2005 U.S.
      National Alcohol Surveys. Among current drinkers, cluster analyses of volume
      drunk in six contexts (restaurants, bars, others' parties, or when spending a
      quiet evening at home, having friends drop over at home, and hanging out in
      public places) were used to classify individuals by their drinking context
      preferences in each gender by ethnicity subgroup. RESULTS: We identified three
      highly similar drinking context-preference clusters within each of the six
      subgroups: (1) bar-plus group (did most drinking in bars, plus much in other
      venues), (2) home group (did most drinking at home, and a fair amount elsewhere),
      and (3) light group (drank almost nothing quietly at home and also less in other
      settings than the other two clusters). For a number of ethnic-by-gender groups,
      context preference group assignment predicted drinking-related problems, over and
      above general drinking patterns. For example, for all groups, the bar-plus
      preference group relative to the light group showed higher risk of arguments,
      fighting, and drunk driving, after taking into account the volume consumed,
      frequency of heavy drinking, age, and year of survey. CONCLUSIONS: Examining
      individuals' preferred drinking contexts may provide important information to
      augment overall drinking patterns in risk and prevention studies.

PMID- 19118388
TI  - Associations between acculturation and alcohol consumption of Latino men in the
      United States.
AB  - OBJECTIVE: This study examined the relationship between acculturation and six
      distinct drinking outcomes. We expected high levels of acculturation to be
      associated with higher odds of being a drinker and, among drinkers, with lower
      frequency of drinking, less alcohol consumption per year, less heavy drinking,
      fewer episodes of drunkenness, and fewer dependence symptoms. METHOD: The data
      consisted of a nationally representative sample of Latino men ages 18 and older
      (N = 784) from the 2005 National Alcohol Survey. The men were predominantly
      Mexican and Mexican American (64%), and most were born outside the United States
      (68%). Analyses included both bivariate and multivariate regression models using
      weights to adjust for sampling and nonresponse. RESULTS: The hypotheses were
      partially supported. Men at high levels of acculturation were more likely than
      their peers at low levels of acculturation to be drinkers but only if they had
      above-average incomes. Counter to expectations, among drinkers there was a
      protective effect of medium, rather than high, levels of acculturation on
      frequency of drinking, volume of alcohol consumed, drinking to drunkenness, and
      dependence symptoms, with a protective effect approaching significance for heavy
      drinking. CONCLUSIONS: The findings have implications for future research and
      public health programs designed to reach Latino men in the United States.

PMID- 19118389
TI  - Impact of substance-use disorder treatment on women involved in prostitution:
      substance use, mental health, and prostitution one year after treatment.
AB  - OBJECTIVE: Prostitution is common among women with substance-use disorders
      (SUDs). However, little is known about the outcomes of SUD treatment for women
      involved in prostitution relative to their peers or the impact of SUD treatment
      on subsequent prostitution. METHOD: Participants were 1,287 women from a national
      study of SUD treatment sites. Women completed a baseline interview at entry to
      SUD treatment and a follow-up interview roughly 1 year after discharge. We
      compared the substance-related and mental health outcomes at follow-up of women
      involved in prostitution and women not involved in prostitution, and determined
      if prostitution declined significantly at follow-up. Among women reporting
      prostitution at baseline (n = 533), we examined whether receipt of specific
      ancillary services (medical, mental health, psychosocial) was associated with
      cessation of prostitution and whether cessation of prostitution was associated
      with better substance-related and mental health outcomes. RESULTS: Women
      reporting prostitution at baseline had more frequent drug and alcohol use,
      reduced abstinence rates, and more mental health symptoms at follow-up compared
      with their peers. However, the rate of prostitution declined from baseline to
      follow-up. Receipt of more mental health and psychosocial services during
      treatment was associated with the cessation of prostitution at follow-up, and
      cessation of prostitution was associated with lower substance use, higher rates
      of abstinence, and fewer mental health symptoms at follow-up. CONCLUSIONS:
      Comprehensive services may be needed to effect significant reductions in
      substance use and mental health symptoms among women engaged in prostitution.

PMID- 19118391
TI  - Three brief alcohol screens for detecting hazardous drinking in incarcerated
      women.
AB  - OBJECTIVE: Screening methods for hazardous drinking have not been evaluated in a
      population of incarcerated women. This study examines abbreviated versions of the
      Alcohol Use Disorders Identification Test (AUDIT) and the National Institute on
      Alcohol Abuse and Alcoholism (NIAAA) heavy episodic drinking criterion in a
      sample of female detainees. METHOD: A total of 2,079 women at the Adult
      Correctional Institute in Rhode Island were approached for screening between
      February 2004 and June 2007. The AUDIT-consumption (AUDIT-C), AUDIT-3, and the
      NIAAA heavy episodic drinking criterion (four or more drinks on one occasion for
      women) were compared with the full AUDIT at different cut points. RESULTS: More
      than 55% of the sample endorsed an AUDIT score of 4 or greater--the NIAAA
      recommended threshold for detecting hazardous drinking. The three-item AUDIT-C
      with a cut score of 3 yielded a classification most consistent with the AUDIT
      score of 4 or more; sensitivity and specificity exceeded .9, and 91.5% of
      participants were correctly classified. The AUDIT-3 and NIAAA episodic drinking
      criteria were less sensitive measures. We found no evidence of interactions
      between the screening instruments and age or ethnicity. CONCLUSIONS: The three
      item AUDIT-C has robust test characteristics for detecting hazardous drinking in
      female inmates. Universal screening for hazardous drinking is recommended for
      incarcerated women, given their high rates of alcohol misuse.

PMID- 19118390
TI  - Revictimization as a moderator of psychosocial risk factors for problem drinking
      in female sexual assault survivors.
AB  - OBJECTIVE: Adult sexual assault (ASA) survivors report greater levels of problem
      drinking than do other women, and research suggests that their coping strategies,
      reactions from their social networks, and traumatic life events affect their
      problem drinking. The links between these factors and problem drinking may be
      moderated by whether survivors are revictimized, yet research has not examined
      this possibility. Therefore, the current study examined psychosocial factors,
      problem drinking, and revictimization in women ASA survivors. METHOD: Community
      dwelling urban women (n = 555) who had experienced an ASA completed a mail survey
      at Time 1 (T1) and were resurveyed 1 year later to examine how revictimization
      between survey waves moderated the effects of coping strategies, social reactions
      to assault disclosures, and traumatic life events on problem drinking at Time 2
      (T2). RESULTS: The findings showed that recent revictimization that occurred
      between surveys was related to increased problem drinking at T2, after T1 problem
      drinking was controlled for. Moderated hierarchical multiple regressions showed
      that survivors who engaged in drinking to cope with distress, who received
      negative social reactions in response to recent assault disclosures, or who
      experienced additional traumatic events had increased T2 problem drinking only if
      they were revictimized since T1. CONCLUSIONS: Psychosocial factors relate to
      increases in problem drinking for sexually revictimized women but not for
      nonrevictimized women. Interventions to reduce problem drinking in women ASA
      survivors should target drinking to cope with assault-related symptomatology,
      informal social networks to improve their supportiveness, and safety issues
      through risk-reduction education and self-defense training for women when
      appropriate.

PMID- 19118392
TI  - Relationships of hazardous alcohol use, alcohol expectancies, and emotional
      commitment to male sexual coercion and aggression in dating couples.
AB  - OBJECTIVE: The current research was designed to identify subgroups among dating
      couples based on individual characteristics and a couple's dyadic pairing that
      contribute to the risk for male perpetration of sexual aggression and female
      victimization. METHOD: Heterosexual dating couples (N = 164) were recruited from
      a large university. They separately completed measures assessing the frequency of
      sexually aggressive acts perpetrated by the male partner (revised Conflict
      Tactics Scales), hazardous alcohol use (AUDIT-C), alcohol expectancies (shortened
      Alcohol Expectancies Questionnaire), emotional commitment, and relationship
      length. RESULTS: A two-step cluster analyses revealed two distinct subgroups of
      dating couples. Dating partners in Cluster 2, compared with Cluster 1, were less
      emotionally committed, in a shorter relationship, engaged in more hazardous
      alcohol use, possessed stronger alcohol expectancies, and were younger. Further,
      male partners in Cluster 2 perpetrated more sexual aggression, sexual coercion,
      and threatened/forced sex compared with men in Cluster 1. CONCLUSIONS: Using
      cluster analytic techniques, this study extended past research by identifying
      individual and couple-level characteristics that contributed to the risk for male
      sexual aggression perpetration and female victimization. Younger couples in the
      early stages of a dating relationship, who are less committed to each other, and
      who are both engaging in hazardous drinking and possess stronger alcohol
      expectancies are more at risk. Including a discussion in prevention programs that
      make individuals cognizant of not only their own but also their partner's
      characteristics as a risk for sexual aggression and coercion might provide young
      adults with better skills to assess risky situations.

PMID- 19118393
TI  - Perceived local enforcement, personal beliefs,and underage drinking: an
      assessment of moderating and main effects.
AB  - OBJECTIVE: Strategies to enforce underage drinking laws are aimed at reducing
      youth access to alcohol from commercial and social sources and deterring its
      possession and use. However, the processes through which enforcement strategies
      may affect underage drinking are not well understood. This study examined three
      possible processes by which perceived enforcement of underage drinking laws and
      personal beliefs (perceived alcohol availability, perceived harm, and personal
      disapproval of alcohol use) may influence alcohol use among adolescents. METHOD:
      Survey data were obtained from 20,747 adolescents (48.3% males) in 115 school
      districts who participated in the 2006 Oregon Healthy Teens survey. Linear
      regression analyses were conducted to examine possible interactive and main
      effects of perceived enforcement and personal beliefs on past-30-day alcohol use.
      Analyses were adjusted for clustering of observations within school districts and
      included student demographics and age of alcohol use initiation as covariates.
      RESULTS: Statistically significant interaction effects on past-30-day alcohol use
      were found for perceived police enforcement and the three personal beliefs
      variables, indicating weaker associations between personal beliefs and past-30
      day alcohol use at higher levels of perceived enforcement. Main effects of
      perceived enforcement and personal beliefs variables were also observed in the
      presence of interaction effects. CONCLUSIONS: Evidence for a moderating effect of
      perceived local enforcement on the relationships between personal beliefs and
      drinking behaviors suggests that the combination of individually focused
      prevention programs and local enforcement of underage drinking laws may have the
      greatest impact on underage drinking.

PMID- 19118394
TI  - Gender-specific intervention to reduce underage drinking among early adolescent
      girls: a test of a computer-mediated, mother-daughter program.
AB  - OBJECTIVE: This study evaluated a gender-specific, computer-mediated intervention
      program to prevent underage drinking among early adolescent girls. METHOD: Study
      participants were adolescent girls and their mothers from New York, New Jersey,
      and Connecticut. Participants completed pretests online and were randomly divided
      between intervention and control arms. Intervention-arm girls and their mothers
      interacted with a computer program aimed to enhance mother-daughter relationships
      and to teach girls skills for managing conflict, resisting media influences,
      refusing alcohol and drugs, and correcting peer norms about underage drinking,
      smoking, and drug use. After intervention, all participants (control and
      intervention) completed posttest and follow-up measurements. RESULTS: Two months
      following program delivery and relative to control-arm participants, intervention
      arm girls and mothers had improved their mother-daughter communication skills and
      their perceptions and applications of parental monitoring and rule-setting
      relative to girls' alcohol use. Also at follow-up, intervention-arm girls had
      improved their conflict management and alcohol use-refusal skills; reported
      healthier normative beliefs about underage drinking; demonstrated greater self
      efficacy about their ability to avoid underage drinking; reported less alcohol
      consumption in the past 7 days, 30 days, and year; and expressed lower intentions
      to drink as adults. CONCLUSIONS: Study findings modestly support the viability of
      a mother-daughter, computer-mediated program to prevent underage drinking among
      adolescent girls. The data have implications for the further development of
      gender-specific approaches to combat increases in alcohol and other substance use
      among American girls.

PMID- 19118395
TI  - Modeling cognitive influences on drinking and alcohol problems.
AB  - OBJECTIVE: We explored the relationships between two domains of alcohol-related
      cognitions (expectations and reasons for drinking) and their associations with
      alcohol consumption and alcohol dependence. It is hypothesized that alcohol
      related cognitions will relate directly to drinking behaviors and indirectly to
      alcohol dependence. METHOD: Data came from the 1995 National Alcohol Survey,
      which included black and Hispanic oversamples. The analysis was restricted to
      2,817 respondents who reported alcohol consumption at least once in the past
      year. Path analysis, including key demographic factors, modeled the associations
      between expectations, reasons for drinking, frequency of heavy drinking, and
      alcohol dependence. RESULTS: Exploratory and confirmatory factor analyses yielded
      separate latent variables for expectations (positive and negative), reasons for
      drinking (social and escape), frequency of heavy alcohol use, and alcohol
      dependence symptoms. Associations between positive expectations and frequency of
      heavy drinking were partially mediated by social and escape reasons for drinking.
      Associations between negative expectancies and alcohol dependence were partially
      mediated by escape reasons for drinking. Associations between reasons for
      drinking and alcohol dependence were partially mediated by the frequency of heavy
      drinking. Associations between demographic variables and alcohol dependence were
      mediated by the frequency of heavy drinking; black race and Hispanic ethnicity
      also showed additional direct effects on dependence. CONCLUSIONS: Alcohol-related
      cognitions exhibit complex associations with drinking behaviors and alcohol
      dependence. Implications for research on ethnic minority health disparities and
      public policy are discussed.

PMID- 19118396
TI  - Family history of alcohol-use disorders and spatial working memory: effects on
      adolescent alcohol expectancies.
AB  - OBJECTIVE: Family history (FH) of alcohol-use disorders (AUDs) has been
      associated with frontal lobe deficits, more positive expectations for alcohol
      effects, and increased risk of developing AUDs. We tested the hypothesis that
      anterior brain regions mediate the relationship between FH of AUDs and alcohol
      expectancies in adolescents. METHOD: Nondrinking adolescents (N = 50) ages 12-14
      completed measures of FH of AUDs, alcohol expectancies, and substance use and
      performed spatial working memory and vigilance tasks during functional magnetic
      resonance imaging. RESULTS: Activation of the anterior cingulate significantly
      predicted alcohol expectancies (R(2)Delta = 9%, beta = .32, F(change) = 6.09,
      1/43 df, p < .05). However, FH of AUDs was not associated with brain response or
      alcohol expectancies. CONCLUSIONS: Although a mediational model was not
      supported, activation in the anterior cingulate was linked to alcohol
      expectancies, such that adolescents with less neural differentiation to task
      demands had more positive expectancies for alcohol's effects. These results
      provide a greater understanding of the interrelations among risk factors for AUD
      and point to individuals who might be targeted for early, cognitively based
      interventions.

PMID- 19118397
TI  - Perceived approval of friends and parents as mediators of the relationship
      between self-determination and drinking.
AB  - OBJECTIVE: Within the context of self-determination theory, individuals vary in
      the extent to which they are oriented toward autonomy and control. Previous
      research on the relationship between motivational orientations and drinking
      behavior among college students has suggested that students who are more
      autonomously oriented consume less alcohol whereas those who are more control
      oriented consume more alcohol. This research evaluated the extent to which these
      relationships are mediated by the perceived approval of friends and parents, both
      of which are important sources of potential influence on the behavior of college
      students. METHOD: First-year students (N = 818, 58% female) who reported one or
      more heavy drinking episodes in the previous month completed online assessments
      of their drinking behavior, autonomous and controlled orientations, and
      perceptions of the approval of drinking (injunctive norms) by important others
      (friends and parents). RESULTS: The results suggested that controlled orientation
      was associated with greater alcohol use and that this association was mediated by
      perceptions of friends being more approving of problematic drinking. In contrast,
      autonomous orientation was associated with less alcohol use and this association
      was mediated by perceptions of friends being less supportive of problematic
      drinking. No support was found for perceptions of parents' approval as a mediator
      of the associations between either orientation and drinking. CONCLUSIONS: The
      findings highlight the importance of perceptions of friends' approval or
      disapproval of problematic drinking in understanding the relationship between
      self-determination and heavy drinking among college students.

PMID- 19118398
TI  - Therapist adherence to a motivational-interviewing intervention improves
      treatment entry for substance-misusing adolescents with low problem perception.
AB  - OBJECTIVE: This study evaluated whether adherence to the Strengths-Oriented
      Referral for Teens (SORT) model, a motivational interviewing (MI)-consistent
      intervention addressing ambivalence about attending treatment, positively
      predicted adolescents' initial-session attendance. METHOD: Therapist adherence
      was rated in 54 audiotaped SORT sessions by coders who were blind to treatment
      entry status. Higher adherence scores reflected greater use of MI and solution
      focused language, discussion of client strengths, and dialogue with families on
      treatment need and options. RESULTS: Therapist adherence during adolescent
      segments interacted with adolescent problem perception. Predicted probabilities
      of attending initial sessions increased for low-problem-perception adolescents at
      increasingly higher therapist adherence. CONCLUSIONS: Although replication
      studies are needed, the SORT model of providing MI-consistent debriefing
      following initial assessments appears to be a promising approach for increasing
      treatment entry. Initial support for the treatment-matching hypothesis was found
      for substance-misusing adolescents contemplating treatment entry.

PMID- 19118399
TI  - A cross-lagged evaluation of eating disorder symptomatology and substance-use
      problems.
AB  - OBJECTIVE: The purpose of this study was to conduct a temporal examination of the
      associations among disordered eating behaviors, substance use, and use-related
      negative consequences in female college students-a population at high risk for
      developing eating and substance-use disorders. METHOD: Participants completed
      assessments of disordered eating behaviors, alcohol and drug use, and use-related
      negative consequences. RESULTS: Results support previous research suggesting that
      disordered eating behaviors are more strongly associated with alcohol- and
      substance-related problems rather than use per se. With respect to temporal
      precedence, results indicated that binge eating preceded alcohol-use problems,
      but a bidirectional relationship was found for vomiting. With regard to drug
      problems, laxatives use preceded drug problems, whereas drug problems preceded
      fasting. These associations were not better accounted for by pre-existing eating
      or substance-use problems or psychiatric distress (e.g., depression, anxiety).
      CONCLUSIONS: This study further supports the importance of assessing
      consequences, in addition to use patterns, when examining substance use in
      individuals demonstrating threshold and subthreshold eating-disordered behaviors.

PMID- 19118400
TI  - Predictors of initial AA-related helping: findings from project MATCH.
AB  - OBJECTIVE: The purpose of this article is to identify the factors that predict
      initial Alcoholics Anonymous (AA)-related helping following treatment admission.
      METHOD: Data were derived from Project MATCH (Matching Alcoholism Treatments to
      Client Heterogeneity), a longitudinal investigation of the efficacy of three
      behavioral treatments for alcohol abuse and dependence. Cox proportional hazard
      regressions were performed to determine the extent to which demographic,
      clinical, belief, and AA factors predicted initial AA-related helping. RESULTS:
      Demographic characteristics, drinking severity, antisocial personality, and
      purpose in life were not associated with initial AA-related helping. Increased
      self-efficacy, faith-based practices, meeting attendance, number of steps worked,
      having a sponsor, and length of sobriety predicted initial AA-related helping.
      Alcoholics reported elevated depressive symptoms before initial AA-related
      helping, lowered depressive symptoms at the start of AA-related helping, and
      similarly lowered depressive symptoms in the interval following initial AA
      related helping. CONCLUSIONS: The profile of prospective helpers in AA is not
      limited to alcoholics from certain backgrounds or higher functioning in terms of
      drinking or clinical severity. To increase participation in AA-related helping,
      and hence outcomes, results suggest strengthening self-efficacy and progress in
      other AA programmatic components.

PMID- 19118401
TI  - Effects of Sunday sales restrictions on overall and day-specific alcohol
      consumption: evidence from Canada.
AB  - OBJECTIVE: The aim of this study was to estimate the effect of Sunday alcohol
      sales policies on day-specific and overall alcohol consumption. METHOD:
      Individual-level data on overall and day-specific alcohol consumption from
      Canada's National Population Health Surveys, 1994-1999, were linked to province
      level policy variation in whether a Sunday sales restriction was present. We
      compared individuals in provinces with sales restrictions with those in provinces
      without such restrictions, and we estimated models of day-specific and overall
      alcohol consumption. We used a standard cross-section model as well as a quasi
      experimental approach that relied on Ontario's liberalization of Sunday sales in
      1997. RESULTS: Sunday sales were associated with a significant increase in
      drinking on Sundays of 7% to 15%. We found evidence of substitution away from
      drinking on Saturdays and no evidence for increases in overall drinking.
      CONCLUSIONS: Our results suggest that repealing Sunday sales prohibitions is
      unlikely to result in increased overall alcohol consumption, although such
      liberalization may change the within-week distribution.

PMID- 19118402
TI  - Gambling, alcohol, and other substance use among youth in the United States.
AB  - OBJECTIVE: Problem gambling has been linked with substance misuse among youth in
      a number of regional studies, yet there have been no large representative U.S.
      surveys of gambling behaviors and substance use among youth. The present study is
      designed to compare the patterns and co-occurrence of gambling and alcohol and
      other substance use among youth in the United States. METHOD: A random telephone
      survey was conducted with 2,274 youth ages 14-21 years old living in households
      in every area of the United States. RESULTS: Problem gambling and substance
      misuse are prevalent among young people. For instance, 17% of youth reported
      gambling 52 or more times in the past year, and the same percentage of youth
      drank five or more drinks on 12 or more days in the past year. Ten percent of
      youth reported having three or more gambling problems in the past year, and 15%
      of young people reported having three or more alcohol problems. Controlling for
      gender, age, and socioeconomic status, black youth have a significantly increased
      probability of frequent gambling compared with other racial/ethnic groups, yet
      they have a significantly decreased probability of heavy drinking. Alcohol
      problems and gambling problems show high co-occurrence, especially for male youth
      and black youth. CONCLUSIONS: Population subgroups with a high co-occurrence of
      alcohol and gambling problems are important for targeted prevention and
      intervention strategies.

PMID- 19118403
TI  - Validation of a DIS-III-R rescoring algorithm for DSM-IV alcohol-use disorders.
AB  - OBJECTIVE: The aim of this study was to evaluate the validity of the Diagnostic
      Interview Schedule, Version III, Revised (DIS-IIIR), rescoring algorithm when
      compared with Diagnostic and Statistical Manual of Mental Disorders, Fourth
      Edition (DSM-IV), diagnoses established using the Composite International
      Diagnostic Interview (CIDI). The research question is "Does our DIS-III-R rescore
      accurately reflect DSM-IV diagnoses established independently using the CIDI?"
      METHOD: One hundred subjects were administered the CIDI and the DISIII-R alcohol
      use modules. The DIS-III-R criteria were rescored to the DSM-IV diagnosis using
      our published algorithm. The specificity of the rescore, along with the
      sensitivity for abuse and dependence diagnoses, was computed. RESULTS: The
      rescoring algorithm showed good sensitivity for lifetime alcohol abuse (60.4%)
      and dependence (80.0%) but poor specificity (0.0%). Current alcohol dependence
      was diagnosed with high sensitivity (100.0%) and moderate specificity (40.2%).
      Current alcohol abuse was diagnosed with poor sensitivity (18.2%). CONCLUSIONS:
      Our algorithm can be used to rescore DIS-III-R data to DSM-IV alcohol-use
      diagnoses, but one must use caution with respect to the timeframe of alcohol-use
      disorders and the specific diagnosis.

PMID- 19118404
TI  - Substitutions of 169Lys and 173Thr in nonstructural protein 1 influence the
      infectivity and pathogenicity of XJ-160 virus.
AB  - An infectious clone (pBR-XJ160) was constructed using the full-length cDNA of the
      Sindbis-like XJ-160 virus. Two nucleotide mutations, causing amino acid changes
      at residue 169 from Lys to Arg and at residue 173 from Thr to Ile in the
      nonstructural protein (nsP) 1 coding region, strongly influenced the infectivity
      of in vitro-synthesized RNA. We used site-directed mutagenesis to obtain clones
      encoding a change to Arg at residue 169 of nsP1 (pBR-169), a change to Ile at
      residue 173 (pBR-173), or both changes (pBR-6973). Infectivity of RNA from pBR
      169 was abolished, but viral forms BR-173 and BR-6973 were obtained from pBR-173
      and pBR-6973, respectively. Further, BR-173 exhibited higher propagation than BR
      XJ160 in cell culture and higher neurovirulence in a suckling mouse model. BR
      6973 possessed an intermediate phenotype. BR-173 and BR-6973 showed increased
      sensitivity to 3-deazaadenosine (3-DZA), which inhibits S-adenosylhomocysteine
      hydrolase. Thus, mutagenesis at residue 169 in the nsP1 region of XJ-160 is
      lethal, but mutation at residue 173 from Thr to Ile enhances viral infectivity
      and neurovirulence and suppresses the lethal effect of the mutation at residue
      169. These mutations might be associated with the RNA methyltransferase (MTase)
      activity of nsP1.

PMID- 19118405
TI  - Quantity discrimination in Tenebrio molitor: evidence of numerosity
      discrimination in an invertebrate?
AB  - Numerosity discrimination, the ability to distinguish between sets with more and
      less items, is recognised as the foundation for higher numerical abilities.
      Understanding numerosity discrimination from a comparative perspective is hence
      pivotal in tracing the evolution of numerical representation systems. However,
      numerosity discrimination has been well studied only in vertebrates, where two
      innate systems of number representation have been described: an 'analog magnitude
      system' used to discriminate among numerosities by representing them as cardinal
      magnitudes and a 'parallel individualisation system' that allows precise
      discrimination among small arrays of items (< or =4) by representing objects
      individually. We investigated the existence of quantity discrimination in an
      insect species (Tenebrio molitor) by using a spontaneous two-choice procedure in
      which males were exposed to substrates bearing odours from different numbers of
      females (< or =4) in increasing numerosity ratios (1:4, 1:3 and 1:2). We show
      that males can discriminate sources of odours reflecting 1 versus 4 and 1 versus
      3 females, but not 2 versus 4 or 1 versus 2, indicating that T. molitor males
      exhibit a marked preference for sources reflecting more female donors only when
      numerosity ratios are below 1:2. We discuss the functional significance of this
      finding and whether our pattern of results could be best explained by summation
      of a non-numerical continuous variable or by the existence of a numerosity
      discrimination mechanism with an operational signature ratio of 1:2.

PMID- 19118406
TI  - Karyotypic and molecular polymorphisms in Ctenomys torquatus (Rodentia:
      Ctenomyidae): taxonomic considerations.
AB  - The rodent genus Ctenomys (tuco-tucos) comprises more than 60 described species,
      and shows extraordinary inter- and intraspecific karyotypic variation. The most
      widely distributed species of Ctenomys in Brazil is C. torquatus. Although
      several cytogenetic studies have been done, the karyotypic variability of this
      species is still poorly known. In this paper we report two new diploid numbers
      for C. torquatus: 2n = 40 and 2n = 42, both showing AN = 72. The new distribution
      limits of C. torquatus here reported include localities in the southern, central
      and western parts of Rio Grande do Sul (RS) State in southern Brazil. The
      phylogenetic relationship between C. torquatus from Alegrete, RS, and Ctenomys
      sp. from Corrientes, Argentina, is described by means of mtDNA cytochrome b
      analysis. Although both entities share similar karyotypes and sperm morphology,
      these two species are not phylogenetically close.

PMID- 19118407
TI  - Cloning, heterologous expression, and functional characterization of the
      nicotinate dehydrogenase gene from Pseudomonas putida KT2440.
AB  - 6-hydroxynicotinate can be used for the production of drugs, pesticides and
      intermediate chemicals. Some Pseudomonas species were reported to be able to
      convert nicotinic acid to 6-hydroxynicotinate by nicotinate dehydrogenase. So
      far, previous reports on NaDH in Pseudomonas genus were confused and
      contradictory each other. Recently, Ashraf et al. reported an NaDH gene cloned
      from Eubacterium barkeri and suggested some deducted NaDH genes from other nine
      bacteria. But they did not demonstrate the activity of recombinant NaDH and did
      not mention NaDH gene in Pseudomonas. In this study we cloned the gene of NaDH,
      ndhSL, from Pseudomonas putida KT2440. NdhSL in P. putida KT2440 is composed of
      two subunits. The small subunit contains [2Fe2S] iron sulfur domain, while the
      large subunit contains domains of molybdenum cofactor and cytochrome c.
      Expression of recombinant ndhSL in P. entomophila L48, which lacks the ability to
      produce 6-hydroxynicotinate, enabled the resting cell and cell extract of
      engineering P. entomophila L48 to hydroxylate nicotinate. Gene knockout and
      recovery studies further confirmed the ndhSL function.

PMID- 19118408
TI  - Subclinical inflammation/oxidation as revealed by altered gene expression
      profiles in subjects with impaired glucose tolerance and Type 2 diabetes
      patients.
AB  - Although subclinical inflammation and oxidative stress are implicated in the
      aetiology of diabetes, there are hardly any studies in prediabetes. Therefore, we
      made an attempt to study the gene expression pattern of certain
      inflammatory/oxidative genes using lymphocytes from Type 2 diabetic patients,
      impaired glucose tolerance (IGT), and normal glucose tolerance (NGT) subjects.
      Compared to NGT group, interleukin-6, tumor necrosis factor-alpha (TNF-alpha),
      p(22)Phox NADPH oxidase, and thioredoxin interacting protein (TXNIP) mRNA levels
      were higher and suppressor of cytokine signaling (SOCS-3) mRNA was lower in
      subjects with IGT and diabetes. The mean (+/-SE) levels of thiobarbituric acid
      reactive substances and protein carbonyl content were also elevated in glucose
      intolerant subjects. In multiple linear regression analysis, TXNIP and TNF-alpha
      showed a significant association with HbA1c even after adjusting for TBARS and
      PCO (TXNIP: beta = 1.70, P < 0.01; TNF-alpha: beta = 1.86, P < 0.01). Increased
      subclinical inflammation/oxidation is seen in Asian Indians with not only Type 2
      diabetes but also IGT.

PMID- 19118409
TI  - Alteration of 11beta-hydroxysteroid dehydrogenase type 1 in skeletal muscle in a
      rat model of type 2 diabetes.
AB  - Recent investigations have demonstrated that activation of 11beta-hydroxysteroid
      dehydrogenase type 1 (11beta-HSD1) in liver and adipose tissue is closely related
      to the pathogenesis of obesity and diabetes. However, the relationship between
      alteration of 11beta-HSD1 and the pathogenesis of type 2 diabetes in skeletal
      muscle is still unclear. A rat model of Type 2 diabetes was developed by high fat
      diet feeding combined with multiple low dose streptozotocin injection (30 mg/kg,
      i.p. twice). Intraperitoneal glucose tolerance test, insulin tolerance test were
      performed. Fasting blood glucose, fasting insulin, total cholesterol,
      triglyceride were measured. The protein and mRNA level of 11beta-HSD1 and
      glucocorticoid receptor in gastrocnemius muscle were determined. The alteration
      of insulin signaling pathway related protein was investigated. We found that the
      protein levels of 11beta-HSD1 and glucocorticoid receptor were significantly
      increased (P < 0.05); the mRNA level of 11beta-HSD1 was also elevated (P < 0.05);
      the mRNA level of glucocorticoid receptor was decreased (P < 0.05). After insulin
      stimulation, diabetic rats had no significant changes in the level of the insulin
      receptor beta-subunit (IR-beta), AKT, as in phosphorylated AKT in the
      gastrocnemius muscle compared to its basal state. Similar results were observed
      in the protein expression level of glucose transporter 4 (GLUT4). Our data
      indicate that the alteration of 11beta-HSD1 at protein and mRNA level may be
      related to the abnormality of insulin signal pathway in skeletal muscle, this
      effect may be mediated by glucocorticoid receptor.

PMID- 19118410
TI  - Molecular dynamics study of the interaction between fatty acid binding proteins
      with palmitate mini-micelles.
AB  - The fatty acid binding proteins (FAPBs) function as intracellular carriers of
      fatty acid (FA) and related compounds. During the digestion of lipids, the local
      concentration of FA exceeds their critical micellar concentration; the excess
      ratio of FA/FABP can be as high as approximately 1,000/1, consequently building
      micelles. Considering that the micelle formation is a rapid process, the FABP
      must be able to remove the mini-micelle. In this study, we describe the results
      of molecular dynamics simulations of liver basic FABP (Lb-FABP), carried out in
      the presence of approximately 20 mM palmitate ions, all in the presence of
      explicit water and at ionic strength of approximately 100 mM, approximating
      physiological conditions. The Lb-FABP appears to react, along with a free FA,
      with mini-micelle creating a stable complex (on the time scale of the
      simulations), which is attached to the anti-portal domain of the protein. The
      complex may be formed by the stepwise addition of free FA or through the
      interaction of a pre-formed mini-micelle with the free protein. The driving force
      of the mini-micelle-FABP complex is a combination of electrostatic attraction
      between the negative carboxylates of the mini-micelle with the positive charge of
      the N terminal amine residues and Lennard-Jones FA-protein interactions. The
      preferred tendency of the mini-micelle to react with the anti-portal domain
      retains the alpha-helixes of the portal region free for its electrostatic
      interaction with the membrane, ensuring a rapid unloading of the cargo on the
      membrane.

PMID- 19118411
TI  - Nanocomposite degradable hydrogels: demonstration of remote controlled
      degradation and drug release.
AB  - PURPOSE: To demonstrate remote controlled degradation of degradable nanocomposite
      hydrogels by application of an alternating magnetic field (AMF). Further, it was
      desired to study the AMF effect on the drug release properties of these systems.
      METHODS: Degradable nanocomposite hydrogels were synthesized by incorporating
      iron oxide nanoparticles into a degradable hydrogel that exhibited temperature
      dependent degradation. Heating, degradation, and drug release studies were
      conducted by application of an AMF to determine if modulation of degradation and
      drug release could be attained. RESULTS: Hydrogels were successfully prepared,
      shown to have temperature dependent degradation, and shown to heat when exposed
      to the AMF. The degradation rate of the exposed samples was demonstrated to be
      higher than control samples, thus modulation of degradation was obtained. The
      release of a model drug from the system was modulated by exposure to the AMF.
      CONCLUSIONS: This is the first demonstration of remote controlled degradation
      using an AMF stimulus. Here, the proof of the concept has been presented, and
      there is great potential to enhance this effect through various methods. The
      ability to remotely control degradation of an implanted device opens a new area
      of improved medical devices.

PMID- 19118412
TI  - Voltammetric bioassay of caffeine using sensor implant.
AB  - In this article, we examined the performance of the voltammetric assay of
      caffeine using DNA immobilized onto a carbon nanotube paste electrode (DPE) and
      compared it with that of an ordinary carbon nanotube paste electrode (PE). Under
      optimal conditions, the working ranges for caffeine were from 0.1 to 12 mg l(-1)
      (for DPE) and 30-230 mg l(-1) (for PE). Detection limits (DLs) of 0.068 mg l(-1)
      (3.50 x 10(-7) M) DPE and 9.94 mg l(-1) (5.12 x 10(-5) M) PE were obtained and
      the relative standard deviation at the caffeine concentration of 5.0 mg l(-1) was
      0.064% (n = 15) DPE under optimum conditions. The sensor could be implanted in a
      leaf skin or animal brain cell, which can then be interfaced with an
      electrochemical workstation. It can be used in real-time in vivo caffeine
      analysis in a live cell or leaf skin.

PMID- 19118413
TI  - Percutaneous endoscopic gastrostomy tube removal and replacement after "buried
      bumper syndrome": the simple way.
AB  - BACKGROUND: Percutaneous endoscopic gastrostomy (PEG) feeding tubes are required
      for an increasing number of patients with long-term nutritional requirements.
      "Buried bumper syndrome" (BBS) occurs in 2-6% of PEG placements. In the past,
      this has been a difficult problem to resolve. The authors aimed to design a safe
      and simple method of dealing with BBS that can be performed by any endoscopist on
      a routine endoscopic list with the patient under sedation. METHODS: For 6 years,
      the authors have used a minimally invasive way to deal with BBS. They have
      successfully treated 20 BBS patients on a routine endoscopy list with the patient
      under sedation. The existing PEG is divided 5 cm from the skin. A pair of stent
      grasping forceps is inserted via the tube. A snare then is passed via the
      gastroscope, caught in the stent-grasping forceps, and brought out via the PEG
      tube. Next, the tube is split as deeply as possible into the PEG exit site, and
      the snare is closed around the tube. Gentle traction is applied along the
      endoscope, allowing the internal bumper to concertina and pop through the mucosa.
      Another PEG can now be placed at a separate site, although the authors have
      successfully used the same tract. RESULTS: All the patients were followed up,
      with no further problems related to BBS. CONCLUSIONS: The authors' method is a
      simple way of addressing the difficult BBS problem. It can be used to remove and
      replace a PEG with a buried bumper on a routine endoscopy list with the patient
      under sedation.

PMID- 19118415
TI  - Experimental trial of transvaginal cholecystectomy: an ex vivo analysis of the
      learning process for a novel single-port technique.
AB  - BACKGROUND: Interest in natural orifice transluminal endoscopic surgery (NOTES)
      has expanded, and the first experiences with patients using different techniques
      have been reported. However, no work has addressed the learning process or the
      limitations of the procedures. The relation between inexperience and
      complications became a major concern after the introduction of laparoscopic
      surgery. This study investigates the learning process for a new technique using
      specially designed instruments in an ex vivo model before clinical application.
      METHODS: Specially designed instruments and a single-port technique using the
      Tuebingen Trainer were used to evaluate instrument and surgeon performance
      (learning curve) in terms of time and errors. A total of 90 procedures performed
      by three surgeons were evaluated. Group and individual learning curves were
      plotted. RESULTS: All the surgeons showed a reduction in both mean
      cholecystectomy time (subject A: 27.2 vs 16.6 min; subject B: 21.4 vs 19.22 min;
      subject C: 21 vs 19.7 min) and mean errors (subject A: 2.8 vs 1.6; subject B: 3.5
      vs 2.6; subject C: 3.5 vs 2). A plateau was reached after approximately 15
      procedures. Group learning curve analysis showed a significant reduction in time
      between the first group (mean, 24.97 +/- 5.8 min) and last group (mean, 19.30 +/-
      3.09 min; F[1,28] = 11.83; p = 0.001) for 15 procedures, as well as reduced
      technical errors in the fifth group, from 3.7 +/- 1.65 to 1.6 +/- 1.04 (F[1,28] =
      8.90; p < 0.01), demonstrating a learning effect. The number of optic and access
      port position changes were recorded, setting a standard for normal instrument
      performance. CONCLUSION: This study shows that the tasks of cholecystectomy can
      be learned safely in a reasonable number of simulations with the new instruments.
      Although this is a new technique, prior laparoscopic surgery experience is
      helpful. The technique offers an advantage over those using flexible endoscopes.

PMID- 19118414
TI  - The value of haptic feedback in conventional and robot-assisted minimal invasive
      surgery and virtual reality training: a current review.
AB  - BACKGROUND: Virtual reality (VR) as surgical training tool has become a state-of
      the-art technique in training and teaching skills for minimally invasive surgery
      (MIS). Although intuitively appealing, the true benefits of haptic (VR training)
      platforms are unknown. Many questions about haptic feedback in the different
      areas of surgical skills (training) need to be answered before adding costly
      haptic feedback in VR simulation for MIS training. This study was designed to
      review the current status and value of haptic feedback in conventional and robot
      assisted MIS and training by using virtual reality simulation. METHODS: A
      systematic review of the literature was undertaken using PubMed and MEDLINE. The
      following search terms were used: Haptic feedback OR Haptics OR Force feedback
      AND/OR Minimal Invasive Surgery AND/OR Minimal Access Surgery AND/OR Robotics
      AND/OR Robotic Surgery AND/OR Endoscopic Surgery AND/OR Virtual Reality AND/OR
      Simulation OR Surgical Training/Education. RESULTS: The results were assessed
      according to level of evidence as reflected by the Oxford Centre of Evidence
      based Medicine Levels of Evidence. CONCLUSIONS: In the current literature, no
      firm consensus exists on the importance of haptic feedback in performing
      minimally invasive surgery. Although the majority of the results show positive
      assessment of the benefits of force feedback, results are ambivalent and not
      unanimous on the subject. Benefits are least disputed when related to surgery
      using robotics, because there is no haptic feedback in currently used robotics.
      The addition of haptics is believed to reduce surgical errors resulting from a
      lack of it, especially in knot tying. Little research has been performed in the
      area of robot-assisted endoscopic surgical training, but results seem promising.
      Concerning VR training, results indicate that haptic feedback is important during
      the early phase of psychomotor skill acquisition.

PMID- 19118416
TI  - Colonic sterilization for natural orifice translumenal endoscopic surgery (NOTES)
      procedures: a comparison of two decontamination protocols.
AB  - BACKGROUND: This study aimed to evaluate the effect of two different
      sterilization protocols on the bacterial counts in the swine colon as preparation
      for natural orifice translumenal endoscopic surgery (NOTES) surgery. METHODS: In
      this study, 16 swine were randomized to two different colonic sterilization
      protocols: low colonic irrigation using 300 ml of a 1:1 dilution of 10% povidone
      iodine (Betadine) with sterile saline, followed by 1 g of cefoxitin dissolved in
      300 ml of saline or two consecutive 300-ml irrigations using a quaternary
      ammonium antimicrobial agent (Onamer M). Colonic cultures were taken before
      colonic cleansing after a decontamination protocol and after completion of the
      NOTES procedure. The Invitrogen live/dead bacterial viability kit was used to
      assess for change in the bacterial load. A qualitative culture of peritoneal
      fluid was obtained at the end of the NOTES procedure. Colon mucosal biopsies
      obtained immediately after the sterilization procedure and at the 2-week necropsy
      point were evaluated for mucosal changes. RESULTS: Protocol 1 resulted in an
      average 93% decrease in live colonic bacteria versus 90% with protocol 2
      (nonsignificant difference). After a NOTES procedure, group 1 had a 62% increase
      in live bacteria and group 2 had a 31% increase (nonsignificant difference).
      Peritoneal cultures also were obtained. Bacteria were isolated from the
      peritoneal fluid of all the animals, and two or more species were isolated from
      75% of the animals. There was no evidence of peritoneal infection at necropsy.
      Reactive epithelial changes and mild inflammation were the only pathologic
      abnormalities. No changes were noted at histologic evaluation of colonic mucosa
      after 2 weeks, demonstrating that these were temporary changes. CONCLUSION:
      Colonic irrigation with Betadine and antibiotics are as effective for bacterial
      decontamination of the swine colon as a quaternary ammonium compound. The results
      of this study support the use of either protocol. Despite thorough
      decontamination, peritoneal contamination occurs. The significance of this for
      humans is unknown.

PMID- 19118417
TI  - Video. When sleeve gastrectomy fails: adding a laparoscopic adjustable gastric
      band to increase restriction.
AB  - The use of laparoscopic sleeve gastrectomy (LSG) as a procedure for morbid
      obesity has recently increased. The LSG procedure is used most often as a part of
      a biliopancreatic diversion with duodenal switch (BPDDS) or as a first stage that
      can be converted to a BPDDS or Roux-en-Y gastric bypass (RYGB). However, the
      surgical indications for LSG have rapidly expanded, and some centers use the
      sleeve as the primary operation for morbid obesity.The utility of LSG as a
      primary procedure is controversial, with consensus lacking in the literature.
      Whether the etiology of failed sufficient weight loss is the result of an
      inadequate sleeve or attributable to dilation or hypertrophy of the sleeve, the
      incidence of failed sleeve gastrectomies may be significant.In the treatment of a
      patient with a failed LSG, the options typically include creation of a tighter
      sleeve or conversion to biliopancreatic diversion or RYGB. These procedures,
      however, are complex and can carry significant morbidity.The authors report a
      case of a morbidly obese 42-year-old man who failed to lose sufficient weight
      after an LSG. Because the patient was dependent on several oral antipsychotic
      medications, he refused any malabsorptive procedure, and a decision was made to
      proceed with laparoscopic adjustable gastric banding (LAGB). The case proceeded
      successfully, and at this writing, 9 months after surgery, the patient has
      achieved a 57% excess weight loss from an original weight of 390 lb.The insertion
      of an LAGB into its normal anatomic position is feasible after a sleeve
      gastrectomy, and its use can induce sufficient restriction and weight loss
      results equivalent to those of a sleeve or band alone and possibly better.

PMID- 19118418
TI  - Laparoscopic transperitoneal inguinal hernia repair (TAPP) after radical
      prostatectomy: is it safe? Results of prospectively collected data of more than
      200 cases.
AB  - BACKGROUND: Feasibility of laparoscopic transperitoneal inguinal hernia repair
      (TAPP) in primary hernias has been well established, but can the TAPP also be
      recommended after radical prostatectomy? METHODS: Our prospectively collected
      patient database was reviewed from March 1996 until December 2006 in order to
      compare operative data and postoperative outcomes in 264 TAPPs after
      prostatectomy with 10,962 TAPPs because of primary hernias. Patients operated
      after prostatectomy were divided into two subgroups (year of surgery March 1996
      July 2002 and August 2002-December 2006, with 132 TAPPs per group) to check for a
      possible learning curve. RESULTS: In the group operated after prostatectomy
      patients were older (70 vs. 59 years), duration of operation was longer (59 vs.
      40 min) and morbidity was higher (5.7 vs. 2.8%), but recurrence rate was similar
      (0.8 vs. 0.7%) as was body mass index (BMI) (25 kg/m(2)). Subgroup analysis
      showed a clear learning curve with a decrease of morbidity (9.8-1.5%) and
      recurrence rate (1.5-0%) but similar results in operation time (60 and 58 min).
      CONCLUSIONS: Even if TAPP after radical prostatectomy is a difficult operation it
      can be performed efficiently and safely. However, for a definite decision
      regarding recurrence rate long-term results have to be waited for.

PMID- 19118419
TI  - Single-trocar cholecystectomy using a flexible endoscope and articulating
      laparoscopic instruments: a bridge to NOTES or the final form?
AB  - INTRODUCTION: NOTES cholecystectomy, may eliminate complications related to
      abdominal incisions. However, the nonmandatory gastrotomy and its safe closure is
      the main controversy accompanying this approach. Transvaginal access has minimal
      closure consequences but the safety of inserting extralong instruments between
      the intestines and having the angle of approach from below rather than from above
      is questionable. We conducted a study for performing cholecystectomy using a
      single laparoscopic trocar. METHODS: The single-trocar cholecystectomy technique
      was developed on five porcine animal models weighing 35-40 kg each. A 15-mm
      trocar was used, inserted transumbilicaly. Retraction of the gallbladder was
      achieved using an endoloop and transabdominal anchoring. Hartman's pouch was
      manipulated with an endoscopic grasper, which was passed through the working
      channel of the endoscope, while dissection of the triangle of Callot was
      performed using articulating laparoscopic instruments. RESULTS: Single-trocar
      cholecystectomy was successfully performed in four of five porcine models.
      Average surgery time was 90 min (35-180 min). The technique was modified and
      improved throughout the study. No intraoperative complications occurred.
      CONCLUSIONS: Single-trocar cholecystectomy is feasible and offers safe approach
      to this procedure. We assume that a single incision at the umbilicus generates
      minimal somatic pain, and achieves excellent cosmetic results. The translation of
      this technique to human subjects seems straightforward and raises the question of
      whether NOTES is the preferred technique for cholecystectomy.

PMID- 19118420
TI  - Hybrid transvaginal cholecystectomy, NOTES, and minilaparoscopy: analysis of a
      prospective clinical series.
AB  - INTRODUCTION: Natural orifice transluminal endoscopic surgery (NOTES) makes it
      possible to perform intraperitoneal surgical procedures with a minimal number of
      access points in the abdominal wall. It is not yet possible to perform these
      interventions without the help of abdominal wall entryways, so these procedures
      are hybrids, a fusion of minilaparoscopy and transluminal endoscopic surgery. In
      this paper we present a prospective clinical series of 15 patients who underwent
      transvaginal hybrid cholecystectomy for cholelithiasis. METHODS: This was a
      prospective clinical series of 15 consecutive female patients, nonrandomly chosen
      and without a control group, who underwent a fusion transvaginal NOTES and
      minilaparoscopy procedure with two entryways for cholelithiasis. One was
      umbilical and measured 5 mm in diameter, and the other was in the right upper
      quadrant and measured 3 mm in diameter. RESULTS: The scheduled surgical
      intervention was performed on the 15 patients in whom it had been indicated.
      There were no intraoperative complications. One patient had mild hematuria that
      resolved in less than 12 h; there were no other complications after average
      follow-up of 124 days. Nine patients were discharged in 24 h, and two were
      discharged less than 12 h after the procedure. DISCUSSION: Hybrid transvaginal
      cholecystectomy is a good surgical model for minimally invasive surgery, a
      combination of NOTES and minilaparoscopy. It can be performed in surgical
      settings where laparoscopy is practised regularly, using the instruments normally
      used for endoscopy and laparoscopic surgery. Owing to the reproducibility of the
      intervention and the ease of vaginal closure, hybrid transvaginal cholecystectomy
      will permit further development of NOTES in the future.

PMID- 19118421
TI  - Can prolonged sick leave after gynecologic surgery be predicted? An observational
      study in The Netherlands.
AB  - BACKGROUND: Sick leave frequently has been used as an outcome to evaluate minimal
      invasive surgery compared with conventional open surgery. However, sick leave is
      determined not only by the surgical approach. Recently, a postoperative recovery
      specific quality-of-life questionnaire, the Recovery Index (RI-10), has been
      developed and validated. This study investigated the relation of the Recovery
      Index 10, the RI-6 (a subset of 6 questions), and the type of surgery to sick
      leave. METHODS: The study enrolled 46 patients with a paid job scheduled for
      elective gynecologic surgery, who filled out the RI-10. After 8 weeks, the
      patients were approached by telephone to give information on their return to
      work. RESULTS: Of the 46 patients, 23 (50%) returned to work completely after 8
      weeks, 14 (30%) resumed work partly, and 9 (20%) did not resume work at all. In
      the analysis, the patients who completely returned to work were compared with
      those who did not return or partially returned. Recovery as expressed in the RI-6
      improved with time after surgery. It appeared that the measurement 2 weeks after
      surgery showed the best discriminative capacity to predict sick leave after 8
      weeks, with an area under the curve of 0.88 (confidence interval, 0.74-1.03). The
      subjective postoperative recovery as expressed by the RI-6 is more closely
      related to the type of surgery (p = 0.001) sick leave is (p = 0.14). CONCLUSIONS:
      The subjective recovery scored by the patient on a questionnaire of six questions
      is a better outcome than sick leave for evaluating surgical approaches. If
      administered 2 weeks after surgery, it may predict prolonged sick leave.

PMID- 19118422
TI  - Prognostic significance of endoscopic ultrasound-defined pleural, pericardial or
      peritoneal fluid in oesophageal cancer.
AB  - BACKGROUND: Endoscopic ultrasound (EUS) is known to detect smaller effusion
      volumes than computerised tomography (CT), yet the outcomes for patients
      diagnosed with oesophageal carcinoma and EUS-defined pleural, pericardial or
      ascitic fluid effusions (EDFE) are unknown. The aim of this study was to
      determine the outcome of multidisciplinary stage directed treatment for such
      patients. METHODS: Forty-nine (9.2%) out of a consecutive 527 patients diagnosed
      with oesophageal cancer from a single regional upper gastrointestinal (GI) cancer
      network were found to have evidence of EDFE undetected by CT. Thirty-nine (79.6%)
      patients had pleural effusions, eight (16.3%) pericardial effusions, and two
      (4.1%) ascites. RESULTS: Twelve (24.4%) underwent surgery, 3 (6.1%) received
      neoadjuvant chemotherapy without subsequent surgery, 12 (24.5%) received
      definitive chemoradiotherapy (dCRT), and 22 (44.9%) received palliative
      treatment. Survival in patients with EDFE was significantly shorter (median and 2
      year survival 15.6 months and 24%, respectively) when compared with patients
      without EDFE (26.7 months and 40%, respectively, p = 0.001), and was unrelated to
      EDFE type (p = 0.192). Two-year survival after oesophagectomy with or without
      neoadjuvant therapy was 45% in patients with EDFE compared with 42% in patients
      without EDFE (p = 0.668). CONCLUSIONS: EDFE was an important adverse prognostic
      indicator, but patients deemed to have operable tumours should still be treated
      with radical intent.

PMID- 19118423
TI  - The use of laparoscopic subtotal cholecystectomy for complicated cholelithiasis.

PMID- 19118424
TI  - Radiation exposure during laparoscopic cholecystectomy with routine
      intraoperative cholangiography.
AB  - BACKGROUND: For many years, intraoperative cholangiography during cholecystectomy
      to aid definition of the biliary anatomy and to detect choledocholithiasis has
      been advocated. Although radiation exposure in fluoroscopic procedures is a
      concern, few available data exist regarding the radiation exposure incurred
      during intraoperative cholangiography. This study aimed to determine the average
      radiation exposure sustained during this procedure. METHODS: Radiation dose data
      were recorded between 5 September 2007 and 21 July 2008 for 108 consecutive
      patients undergoing laparoscopic cholecystectomy with intraoperative
      cholangiography. Dose area product values were used to calculate the entrance
      skin dose, an indicator of potential skin damage, and the effective dose, an
      indicator of long-term cancer risk, for each patient. RESULTS: The median age of
      the 108 patients (67% females) included in the data analysis was 51 years (range,
      17-87 years). The mean entrance skin dose during intraoperative cholangiography
      was 0.0069 +/- 0.0066 Gy, and the mean effective dose was 0.18 +/- 0.17 mSv. No
      results exceeded the threshold of 2 Gy for skin damage, and the lifetime risk for
      the development of new cancer due to intraoperative cholangiography was less than
      0.001%. CONCLUSION: Radiation doses administered during intraoperative
      cholangiography are safe and do not represent a contraindication to this
      procedure.

PMID- 19118425
TI  - Natural orifice translumenal endoscopic surgery: critical appraisal of
      applications in clinical practice.
AB  - BACKGROUND: Natural orifice translumenal endoscopic surgery (NOTES), with its
      focus on eliminating incision-related complications, promises to revolutionize
      the way surgery is performed. This study aimed to summarize the clinical
      applications of NOTES for humans, outline the techniques used, and discuss the
      complications and limitations of current techniques. METHODS: A literature search
      was performed using PubMed and Medline search tools to review the extent and
      outcomes of human procedures undertaken using the NOTES technique in its pure
      form or as a hybrid procedure reported until July 2008. The end points were the
      types of operation performed, the approach and technique used for each operation,
      and the procedure-related complications and technical limitations. RESULTS: This
      review considered 16 publications reporting on 49 human subjects. All the studies
      except three used hybrid NOTES procedures, with varying amounts of transabdominal
      assistance. Three transvaginal cholecystectomies, one transvaginal appendectomy,
      and eight transgastric appendectomies have been performed using a pure NOTES
      technique. To date, 15 NOTES transvaginal cholecystectomies and 10 NOTES
      appendectomies (8 transgastric and 2 transvaginal) are reported. Other procedures
      including peritoneoscopy and sigmoid colectomy are described. Three cases of
      minor morbidity are reported and no mortality. CONCLUSIONS: Although initial
      human results seem encouraging, it is important that this research be conducted
      in a way that minimizes bad publicity and describes both favorable and adverse
      outcomes. Robust trials must be conducted at established centers with appropriate
      experience and institutional board ethical review to allow safe introduction of
      this novel technique, with adequate and expedient reporting of serious adverse
      events. The limitations of the current tools and methods are discussed, and
      suggestions are made for further improvements in the technology to facilitate
      NOTES operations.

PMID- 19118426
TI  - Feasibility of laparoscopic Nissen fundoplication as a day-case procedure.
AB  - BACKGROUND: The aim of this prospective double-cohort pilot study is to evaluate
      the feasibility and desirability of laparoscopic Nissen fundoplication (LNF)
      performed in day-care when compared with laparoscopic cholecystectomy (LC) in day
      care. METHODS: Patients who underwent a LNF in day-care were prospectively
      evaluated. LNF patients were treated according to LC in day-care protocol.
      Outcome parameters were EQ-5D, visual analogue scale (VAS), and patient
      satisfaction. RESULTS: From October 2005 to March 2008, 22 patients underwent LNF
      and 48 patients LC in day-care. After LNF, 21 out of 22 (95%) patients were
      discharged the same day. Seven (32%) patients were seen postoperatively in the
      Emergency Department with dysphagia or pain and two (9%) patients were
      readmitted. After LC, 45 out of 48 (94%) patients were discharged the same day.
      Six (12.5%) patients were seen postoperatively in the Emergency Department
      because of wound infection or pain and three (6%) were readmitted. EQ-5D and VAS
      scores were significantly worse after LNF in day-care (repeated measurements, p <
      0.0001 and p < 0.0001). In a telephone survey 66.7% preferred a short hospital
      stay over day-care surgery after LNF compared with 30.9% after LC (p = 0.011).
      CONCLUSIONS: LNF in day-care is feasible and safe, but postoperative pain scores
      are high and most prefer short hospital stay.

PMID- 19118427
TI  - Meaningful assessment method for laparoscopic suturing training in augmented
      reality.
AB  - BACKGROUND: To be an effective training tool, a laparoscopic simulator has to
      provide metrics that are meaningful and informative to the trainee. Time, path
      length and smoothness are often used parameters, but are not very informative on
      the quality of the performance. This study aims to validate a newly developed
      assessment method for laparoscopic suturing on the ProMIS augmented reality
      simulator, and compares it with scores of objective observers. METHODS: Twenty
      four participants practised their suturing skills on the augmented reality
      suturing module: experienced participants (n = 10), >50 clinical laparoscopic
      suturing experience; and novice participants (n = 14), without laparoscopic
      experience. The performances were recorded and assessed by two unrelated
      observers and compared with the assessment scores. The assessment score was a
      calculation of time spent in the correct area and quality (strength) of the knot.
      To test the accuracy of the individual assessment parameters, we compared these
      with each other. RESULTS: The experienced participants had significantly higher
      performance scores than the novice participants in the beginner-level mode (mean
      95.73 vs. 60.89, standard deviation 2.63 vs. 17.09, p < 0.001, independent t
      test). The performance scores of the assessment method (n = 43) correlated
      significantly with the scorings of the objective observers (Spearman's rho 0.672;
      p < 0.001). The parameter time spent in correct area had a calculated significant
      correlation with the strength of the knot (n = 229, Spearman's rho 0.257, p <
      0.001), but this was clinically irrelevant. CONCLUSION: This assessment method is
      a valid tool for objectively assessing laparoscopic suturing skills. Although
      assessment parameters can correlate, to provide informative feedback it is
      important to combine meaningful measurements in the assessment of suturing
      skills.

PMID- 19118428
TI  - Transumbilical laparoscopically assisted appendectomy in children.

PMID- 19118429
TI  - Utility of endoscopy in patients with incidental gastrointestinal luminal wall
      thickening detected with CT.
AB  - BACKGROUND: Reports of incidental gastrointestinal luminal wall thickening
      (IGILWT) on computed tomography (CT) in patients without gastrointestinal
      complaints are not rare. Currently there is no consensus about what to do in
      those cases. The aim of this study was to evaluate the utility of endoscopic
      study in asymptomatic patients with IGILWT. MATERIAL AND METHODS: Retrospective
      analysis of data obtained prospectively between September 2004 and March 2007 was
      carried out. Patients without gastrointestinal symptoms/signs with IGILWT and
      assessed by endoscopy were included. The endoscopic findings were classified as
      follows: normal, abnormal or nonspecific. RESULTS: A total of 10,161
      abdominal/pelvic CT scans were performed. Thirty-one patients were included (14
      women and 17 men). Median age was 59 years (19-84 years). Distribution of IGILWT
      along the gastrointestinal (GI) tract was as follows: 1 esophagus, 19 stomach, 1
      small-bowel, and 10 colon. Endoscopy was normal in 19 cases (61.2%) and
      abnormal/nonspecific in 12 cases (38.8%). Nine (29%) patients had cancer as a
      final diagnosis (gastric cancer in six, colon cancer in two, and non-Hodgkin's
      lymphoma in one). On multivariate analysis hemoglobin <12 g/dl was the only
      significant variable to predict an abnormal result by endoscopy. CONCLUSION:
      Endoscopic study is useful in patients with IGILWT. More than one-third of
      patients with IGILWT have a significant finding by endoscopic evaluation, mainly
      cancer. Absence of GI symptoms/signs, age or gender are not valid criteria to
      decide about further endoscopic evaluation.

PMID- 19118430
TI  - Outcomes analysis of laparoscopic ventral hernia repair in transplant patients.
AB  - BACKGROUND AND AIM: Postoperative wound complications are minimized after
      laparoscopic ventral hernia repair (LVHR) while maintaining low recurrence rates
      and acceptable morbidity. The purpose of this study is to evaluate efficacy and
      safety of LVHR in patients after organ transplantation in comparison to a large
      cohort of nontransplantation patients after LVHR. METHODS: A retrospective,
      institutional review board (IRB)-approved review was performed on 347 patients
      who underwent LVHR between July 2000 and December 2007. RESULTS: LVHR was
      successfully completed in 38/38 transplantation patients (n = 21 liver, n = 5
      cardiac, n = 8 kidney, n = 1 lung/kidney, n = 2 kidney/pancreas, n = 1 double
      lung) without conversion and in 301/309 (97.4%) nontransplant patients. Previous
      hernia repairs were attempted in 5/38 (13.2%) of the transplant patients and
      108/309 (35.0%) of nontransplantation patients. Mean defect size was 256 cm(2) (p
      < 0.00001) and mesh size 780 cm(2) (p < 0.00001) in the transplantation patients,
      and 140 cm(2) and 426 cm(2) in nontransplantation patients, respectively. Mean
      operating time was similar between the two groups (216.9 min versus 184.0 min).
      Perioperative complication rate was similar between groups (34.2% versus 34.3%, p
      = 1.0). There were three (1.0%) mesh infections and two (0.6%) mortalities in the
      nontransplantation patients and one mesh infection and no mortalities in the
      transplantation group. At mean follow-up of 20.0 (range 1.1-41) months in the
      transplantation group and 5.0 (range 1-38) months in the nontransplantation
      group, the hernia recurrence rate was 7.9% and 2.9%, respectively (p = 0.1330).
      CONCLUSION: Perioperative complication and hernia recurrence rates in transplant
      patients after LVHR are comparable to nontransplant patients, although the
      transplantation patients had significantly larger hernias. LVHR should be
      considered to manage ventral incisional hernias post transplantation.

PMID- 19118431
TI  - Antegrade stenting in laparoscopic pyeloplasty: feasibility of the technique and
      time required for stent insertion.
AB  - BACKGROUND: This study aimed to evaluate the authors' initial experience with
      antegrade stenting. It focused on the success rate, time required for stent
      insertion, possible complications, and relative solutions in the first 44
      procedures. METHODS: Between March 2005 and April 2008, 44 patients (21 women and
      23 men) with a mean age of 33 years (range, 17-59 years) underwent
      transperitoneal laparoscopic Anderson-Hynes pyeloplasty in the authors'
      department. Antegrade stenting was attempted for all the patients. The time
      required for stent insertion was recorded as the time from cannula insertion to
      the correct positioning of the stent in the pelvis. A 4.8-Fr, 26-cm stent was the
      stent of choice for the first four cases. Then the 6-Fr, 26-cm stent was adopted
      for all the remaining patients except for one, for whom a 6-Fr, 28-cm stent was
      adopted. RESULTS: The mean operative time was 197 min (median, 180 min; range,
      150-390 min). No conversions to open surgery were required. The stent was
      positioned correctly in the bladder at the end of the antegrade procedure in
      97.7% of the patients without the need for a postoperative X-ray in 95% of the
      cases. The mean time required for antegrade insertion of the stent was 7 min 30 s
      (median, 6 min 13 s; range, 3 min 40 s to 22 min 30 s). In the final 12
      procedures, the time for stent insertion was constantly reduced to a mean of 4
      min 10 s (median, 4 min; range, 3 min 40 s to 7 min). Neither intraoperative nor
      postoperative complications related to antegrade stent positioning were observed.
      CONCLUSION: Our data confirm the antegrade procedure to be an easy-to-learn,
      safe, and reliable stenting technique, with an overall mean time of 7 min 30 s
      required for insertion, and with a mean time of 4 min 10 s required for insertion
      in the final 12 procedures. It obviates the problem of having the stent in the
      renal pelvis during dissection and suturing and of repositioning the patient onto
      the flank for the laparoscopic procedure.

PMID- 19118432
TI  - Risk factors for cholecystectomy in patients with gallbladder stones after
      endoscopic clearance of common bile duct stones.
AB  - BACKGROUND: Cholecystectomy usually is recommended for patients with gallbladder
      (GB) stones who previously underwent endoscopic removal of common bile duct (CBD)
      stones. However, in practice, many patients still have GB stones after
      improvement of their biliary symptoms. This study aimed to evaluate risk factors
      for cholecystectomy in patients with GB stones after complete endoscopic
      clearance of CBD stones. METHODS: From August 2003 to April 2006, the medical
      data of 61 patients with concomitant GB stones who underwent complete endoscopic
      clearance of CBD stones were reviewed retrospectively. The risk factors for
      subsequent cholecystectomy were evaluated during a 24-month of follow-up period.
      RESULTS: Among the 61 patients, 12 (19.7%) subsequently required cholecystectomy
      for recurrence of biliary symptoms, and 11 of these 12 patients (91.7%) needed
      cholecystectomy within 12 months. Gallbladder stones 10 mm or larger (p = 0.037)
      and the acute pancreatitis (p = 0.049) were the independent risk factors for
      subsequent cholecystectomy. The actuarial probability of remaining free of
      subsequent cholecystectomy during the follow-up period was higher for the
      patients with GB stones smaller than 10 mm than for the patients with GB stones
      10 mm or larger (86.7% vs. 62.5%; p = 0.037). In addition, the patients with
      acute pancreatitis had a higher tendency for subsequent cholecystectomy than the
      patients without acute pancreatitis (50% vs. 16.4%; p = 0.078). CONCLUSIONS: Only
      a small number of patients subsequently needed to undergo cholecystectomy for
      recurrence of biliary symptoms, and most events developed within 12 months. For
      the patients with GB stones 10 mm or larger or acute pancreatitis, prophylactic
      cholecystectomy is strongly recommended after complete clearance of CBD stones.

PMID- 19118433
TI  - Laparoscopic resection of extraperitoneal rectal cancer: a comparative analysis
      with open resection.
AB  - PURPOSE: The aim of this study was to compare the outcomes of laparoscopic
      surgery with those of open resection in patients with extraperitoneal rectal
      cancer. METHODS: Five hundred forty-four patients with extraperitoneal rectal
      cancer who underwent curative resection between 1996 and 2007 were included.
      Patients were divided into a laparoscopic surgery group (LAP, n = 170) and an
      open surgery group (OPEN, n = 374). RESULTS: Morbidity requiring surgical
      correction was 5.8% in the LAP group and 4.8% in the OPEN group (p = 0.75). The
      anastomotic leakage rate was similar in both groups (5.7% in both; p = 0.98).
      Differences were found in preoperative carcinoembryonic antigen (CEA) (LAP group
      4.6 ng/ml, OPEN group 7.7 ng/ml, p = 0.001), sphincter preservation (LAP group
      82.9%, OPEN group 69.8%, p = 0.001), and mean distance from anal verge (LAP group
      4.6 cm, OPEN group 5.2 cm, p = 0.002). Local recurrence and metastasis were
      similar by stage. CONCLUSIONS: The results of this study show that laparoscopic
      resection of extraperitoneal rectal cancer was safe and effective.

PMID- 19118434
TI  - A new electrocautery pleural biopsy technique using an insulated-tip diathermic
      knife during semirigid pleuroscopy.
AB  - BACKGROUND: The biopsy size obtained with standard flexible forceps (SFF) during
      semirigid pleuroscopy is often insufficient for pathological examination. An
      insulated-tip diathermic knife (IT knife) allows safe resection of a larger
      lesion during gastrointestinal endoscopy. We sought to validate an electrocautery
      pleural biopsy technique using the IT knife during semirigid pleuroscopy. We
      compared the diagnosis of specimens obtained using the IT knife and SFF in 20
      subjects with unexplained pleural effusion, and reviewed pleuroscopic parameters
      such as complications, procedure time, and diameter of the specimens. METHODS:
      After injecting saline with lidocaine and epinephrine below the affected pleura,
      the lesion was incised in a circular shape with full thickness by manipulating
      the IT knife. RESULTS: Diagnostic yields from specimens obtained with the IT
      knife and SFF were 85% (17 of 20 cases) and 60% (12 of 20 cases), respectively.
      The IT knife biopsy was superior to SFF in 8 of 20 patients (malignant pleural
      mesothelioma in three, nonspecific inflammation in two, metastatic breast cancer
      in one, and tuberculosis in one). These pleural lesions revealed thickened,
      smooth abnormal appearances. The overall diagnostic yield for both IT knife and
      SFF was 100%. Median time of the procedure, from first pleural injection to
      specimen removal, was 21 min (range 12-92 min), and median diameter of specimen
      was 13 mm (range 6-23 mm). There were no severe complications during the
      procedure. CONCLUSIONS: Electrocautery biopsy using the IT knife during semirigid
      pleuroscopy has great potential for diagnosing smooth abnormal pleura which are
      difficult to biopsy with SFF.

PMID- 19118435
TI  - Laparoscopic parastomal hernia repair using a keyhole technique results in a high
      recurrence rate.
AB  - INTRODUCTION: Parastomal herniation is a common complication of stoma formation,
      and its operative treatment is notoriously difficult. Recently we have reported
      the promising short-term results of a keyhole technique in which a Gore-Tex Dual
      Mesh with a central keyhole is laparoscopically fashioned around the bowel to
      close the hernia. In the long-term, recurrence is one of the major issues in
      hernia repair, therefore, this aspect was prospectively investigated. METHODS:
      Since 2002, a total of 55 consecutive patients (27 men; median age, 63 years)
      with a symptomatic primary (n = 45) or recurrent parastomal hernia (n = 10) were
      electively operated using this technique. Patients were invited to the outpatient
      clinic on a regular basis and were examined for the occurrence of a recurrent
      hernia. At the last visit, all patients were asked to complete a short
      questionnaire. RESULTS: Median follow-up (98%) was 36 (range, 12-72) months.
      During follow-up a recurrent parastomal hernia was diagnosed in 20 patients
      (37%). Three recurrences were asymptomatic and were treated conservatively. The
      other 17 patients (85%) developed mild-to-severe symptoms necessitating redo
      surgery in 9 (45%) patients. Surprisingly, satisfaction with the procedure was
      high among patients (89%), even in the presence of a recurrence. Patients who
      reported unsatisfactory results belonged mainly to the group in whom the initial
      laparoscopic approach had to be converted to an open procedure. CONCLUSIONS:
      Based on the results from the present study, which represents one of the largest
      patient series with the longest follow up available to date, it is concluded that
      laparoscopic parastomal hernia repair using a keyhole technique has an
      intolerably high recurrence rate with the currently available meshes. A new mesh
      with a less pliable central part and without the tendency to shrink is awaited.

PMID- 19118436
TI  - Transumbilical single-port laparoscopic cholecystectomy : scarless
      cholecystectomy.
AB  - BACKGROUND: Many laparoscopic surgeons have been attempting to reduce incisional
      morbidity and improve cosmetic outcomes by using fewer and smaller ports. We
      performed transumbilical single-port laparoscopic cholecystectomy (TUSPLC) in 15
      patients with cholelithiasis by using a special "single-port" with virtually no
      scar. METHODS: We used an extra-small wound retractor and a surgical glove as the
      "single-port." The wound retractor was set up through the small umbilical
      incision and the surgical glove attached with one trocar and two pipes was then
      fixed to the outer ring of the wound retractor. The commonly used trocar and two
      slim pipes attached to the surgical glove served as three working channels. Using
      this single-port and conventional laparoscopic instruments, such as a straight 5
      mm dissector, grasper, scissors, and a 30-degree 5-mm rigid laparoscope, we
      performed TUSPLC in 15 patients with cholelithiasis. The overall procedure was
      similar to three-port laparoscopic cholecystectomy. RESULTS: Fifteen well
      selected patients with cholelithiasis underwent TUSPLC (4 males and 11 females;
      mean age, 39 (range, 29-63) years). Body mass index ranged from 20 to 34 (mean,
      25.2). No case required extra-umbilical skin incisions or conversion to standard
      laparoscopy. The mean operative time was 79 (range, 35-165) min. Blood loss was
      minimal in all cases. The mean postoperative hospital stay was 1.6 (range, 1.0
      2.5) days. No postoperative complications were observed. CONCLUSIONS: The results
      of our initial experience of TUSPLC in 15 well-selected patients with
      cholelithiasis are encouraging. All procedures were completed successfully within
      a reasonable time. No extra-umbilical incisions were used and virtually no scar
      remained. TUSPLC could be a promising alternative method for the treatment of
      some patients with symptomatic gallstone disease as scarless abdominal surgery.

PMID- 19118437
TI  - Indexes of surgical quality in gastric cancer surgery: experience of an Italian
      network.
AB  - BACKGROUND: Short-term results of gastric cancer surgery vary remarkably
      worldwide, and international surgical quality criteria are urgently needed. To
      contribute to defining these criteria, we reviewed short-term results of
      gastrectomy for gastric cancer in three centers of the Italian Research Group for
      Gastric Cancer, with an average of 24.7, 29.5, and 18 gastrectomies per year.
      METHODS: Between 1988 and 2002, 1,032 patients underwent gastrectomy for gastric
      cancer in Verona, Siena, and Padua. D1, D2, and D3 lymphadenectomy were
      performed, respectively, in 228, 584, and 220 cases. RESULTS: The median number
      of retrieved lymph nodes was 14 (interquartile range 9-18.75) after D1, 29 (21
      38) after D2, and 46.5 (37-57) after D3. Fewer than 15 nodes were retrieved in
      54.5%, 6.2%, and 1.4% of cases undergoing, respectively, D1, D2, and D3. Adjacent
      organ removal was rare during D1 (splenectomy: 6.1%, splenopancreasectomy: 1.8%),
      and quite common during D3 (11.4%, 11.4%). Forty patients (3.9%) died
      postoperatively. Neither postoperative morbidity nor mortality was significantly
      associated with extension of lymphadenectomy. CONCLUSION: We conclude that at
      least D2 lymphadenectomy is necessary to achieve adequate disease staging (>or=15
      nodes retrieved). Spleen and pancreas tail are more frequently removed during D3,
      but this removal is not associated with higher postoperative morbidity or
      mortality.

PMID- 19118438
TI  - Dihydro-alpha-lipoic acid has more potent cytotoxicity than alpha-lipoic acid.
AB  - Alpha-lipoic acid has been shown to possess cancer-cell-killing activity via
      activation of the apoptosis pathway. In this study, the cytotoxic activities of
      alpha-lipoic and dihydro-alpha-lipoic acid were compared in HL-60 cells. The cell
      killing activity of dihydro-alpha-lipoic acid was higher than that of alpha
      lipoic acid. Both alpha-lipoic and dihydro-alpha-lipoic acid induced caspase-3
      cleavage and internucleosomal DNA fragmentation in treated cells. On the other
      hand, apparent necrotic or late-stage apoptotic cell populations could be
      detected in dihydro-alpha-lipoic acid cells but not in those treated with alpha
      lipoic acid. Moreover, dihydro-alpha-lipoic acid, but not alpha-lipoic acid,
      induced marked mitochondrial permeability transition. Antioxidants could not
      prevent dihydro-alpha-lipoic- or alpha-lipoic-acid-induced cell death. In
      addition, dihydro-alpha-lipoic and alpha-lipoic acid did not up-regulate cellular
      reactive oxygen level. These results indicated that dihydro-alpha-lipoic acid
      exerts more potent cytotoxicity than alpha-lipoic acid through different
      cytotoxic actions.

PMID- 19118440
TI  - Isolation and culture of human umbilical artery smooth muscle cells expressing
      functional calcium channels.
AB  - The human umbilical cord is a biological sample that can be easily obtained just
      after birth. A methodology was developed to perform cultures of human umbilical
      artery smooth muscle cells (HUASMC) expressing contractile proteins and
      functional ionic channels. To avoid fibroblast and endothelial cell
      contamination, we mechanically separated the tunica media, which only contains
      HUASMC and matrix proteins. To isolate the cells, collagenase V and elastase were
      used as hydrolyzing enzymes. The isolated cells were plated in collagen-coated
      dishes to obtain cultures of HUASMC. The cells obtained after different passages
      (1 to 6) exhibit the characteristic vascular smooth cell morphology and express
      smooth muscle alpha-2 actin, myosin heavy chain SM1, and alpha subunits of L- and
      T-type calcium channels (Cav 1.2, Cav 1.2, and Cav 3.2). Electrophysiology
      recordings for L- and T-type calcium channels were made, indicating that these
      channels are functional in the cultured cells. In conclusion, the procedure
      developed allows obtaining cultures of HUASMC expressing contractile proteins and
      also functional ionic channels. These cells could be used to study cellular and
      molecular aspects about the regulation of the vascular function.

PMID- 19118441
TI  - Goat serum as an alternative to establish cell culture from Indian major carp,
      Cirrhinus mrigala.
AB  - Serum from goat, calf, and chicken sources were evaluated in terms of attachment,
      growth, and proliferation of explants of Indian major carp, Cirrhinus mrigala.
      The attachment of explants viz. heart, liver, and kidney was directly
      proportional to the concentration of the serum. Among these sera, the highest
      percentage of attachment, growth, and proliferation was recorded for 10% goat
      serum and 15% newborn calf serum without affecting their cell morphology. On
      contrary to these sera, chicken serum at 15% concentration was found to be mildly
      toxic for all the explants. The cell count was significantly high for the kidney,
      liver, and heart at 10% goat serum among all the tested sera as well as
      concentration. Similarly, the liver, heart, and kidney explants were found to
      survive up to the tenth, seventh, and ninth passage, respectively. Therefore, the
      goat serum at 10% concentration can be used as effectively as newborn calf serum
      for routine culture of fish cells.

PMID- 19118439
TI  - Granulocytic differentiation of HL-60 promyelocytic leukemia cells is associated
      with increased expression of Cul5.
AB  - The human HL-60 promyelocytic leukemia cell line has been widely used as a model
      for studying granulocytic differentiation. All-trans retinoic acid (ATRA)
      treatment of HL-60 cells promotes granulocytic differentiation and is effective
      as differentiation therapy for patients with acute promyelocytic leukemia. The
      identification of genes that are transcriptionally regulated by ATRA has provided
      insight into granulocytic differentiation and differentiation therapy. The Asb-2
      (ankyrin repeat SOCS box 2) gene has previously been identified as a
      transcriptional target in ATRA-treated HL-60 cells. The ASB-2 protein forms an E3
      ubiquitin ligase complex with the proteins, Cul5, regulator of cullin 2 (ROC2),
      and elongin B and C. The purpose of this study was to determine if there is
      increased expression of Cul5 during granulocytic differentiation of HL-60 cells.
      To induce granulocytic differentiation, HL-60 cells were treated for 5 d with
      ATRA and differentiation was confirmed by examining superoxide anion production,
      nuclear morphology, and changes in the expression of CD11b, CD13, and CD15.
      Quantitative real-time RT-PCR was used to measure Cul5 mRNA expression and also
      the expression of other components of the E3 ubiquitin ligase (ASB-2, ROC2,
      elongin B and C). Granulocytic differentiation of HL-60 cells was associated with
      a 1.6-, 1.7-, and 23-fold statistically significant (P <or= 0.05) increase in
      mRNA expression for Cul5, ROC2, and ASB-2, respectively. No significant change
      was found in elongin B and C mRNA expression. Using Western blot analysis, the
      expression of Cul5 protein was increased 6.5-fold with granulocytic
      differentiation of the HL-60 cells. Increased expression of multiple components
      of the Cul5-containing E3 ubiquitin ligase complex with ATRA treatment of HL-60
      cells indicates that this complex may play an important role in granulocytic
      differentiation.

PMID- 19118442
TI  - Is there a "continental" view of health economics evaluation?

PMID- 19118443
TI  - Studies on residues of pesticides used in rape plants protection in surface
      waters of intensively exploited arable lands in Wielkopolska Province of Poland.
AB  - Samples of surface waters of intensively exploited arable lands in Wielkopolska
      Province of Poland were collected in 2006 and 2007. The studies included 13
      insecticides used in rape plants protection against pests. All selected
      pesticides were extracted from water samples by means of solid phase extraction
      (SPE, carbon black) followed by reverse phase ultra performance liquid
      chromatography analysis with quadrupole mass detection (RP-UPLC-MS/MS). Totally,
      123 samples from lakes, rivers, ponds, field watercourses and drainages were
      collected (i.e. 79 and 44 in 2006 and 2007, respectively). Of all samples, 36
      (29.3 %) were contaminated with residues of plant protection products used for
      protection of rape crops. Contamination with thiametoxam and acetamiprid in 17.1
      % and 11.4 % of the samples, respectively, were mostly detected, and the highest
      concentration was determined in sample from field watercourse taken in spring
      2007 containing 1.341 microg/l of acetamiprid. Totally, ten of thirteen studied
      insecticides were found; however, concentrations of their residues were usually
      very low. Among all analyzed samples only three exceeded the level of plant
      protection products established in Directive 2000/60/EC on the level of maximum
      admissible concentrations (MAC) of harmful substances in water. Although
      condition of Wielkopolan waters analyzed within the framework of this paper is
      not alarming, there is a need to take measures directed towards systematic
      monitoring contamination of water with pesticides used currently in intensive
      plant production.

PMID- 19118444
TI  - EDTA as a potential agent preventing formation of Staphylococcus epidermidis
      biofilm on polichloride vinyl biomaterials.
AB  - Polichloride vinyl (PCV) is a widely used thermoplastic polymer, also in the
      production of medical devices. In the present study we assess the influence of
      EDTA in vitro on the biofilm structure formed by Staphylococcus epidermidis
      isolates on PCV biomaterials (Nelaton and Thorax catheters). The 6 strains of S.
      epidermidis were isolated from nasopharynx of hospitalised patients. It was found
      that all isolates were able to form the biofilm on both PCV biomaterials,
      irrespective of adhesion properties (cell surface properties, ability to slime
      production, minimal time needed for adhesion). The EDTA showed bacteriostatic
      effect against planktonic cells of the isolates (MIC = 0.25-0.5 mmol/l; MBC =
      10.0- >25.0 mmol/l; MBC/MIC = 20, 30, 40, >50). The adhesion process and also
      formation of the biofilm was inhibited by EDTA at concentrations 1.0-2.0 mmol/l
      (2-8 x MIC). The eradication of the mature biofilm was achieved at 2.0-4.0 mmol/l
      EDTA (4-8 x MIC ) for two strains, while for the other four isolates,
      concentration of EDTA needed for eradication effect was >32 mmol/l (> 128 x MIC
      ). Data obtained in this paper suggest that EDTA may be regarded as a useful
      agent preventing formation of the S. epidermidis biofilm on PCV biomaterials.

PMID- 19118446
TI  - Presto change-o: the epithelial-mesenchymal transition.

PMID- 19118445
TI  - Endotoxin exposure in sewage treatment workers: investigation of exposure
      variability and comparison of analytical techniques.
AB  - INTRODUCTION: Objectives were to give an overview of endotoxin exposure and its
      determinants in sewage treatment workers, and to study exposure to culturable and
      non-culturable microorganisms and the applicability of the LAL assay in this work
      environment. MATERIAL AND METHODS: In 43 Dutch sewage treatment plants 470 full
      shift, 123 task-based personal and 54 stationary inhalable dust samples were
      collected. Endotoxin concentration was determined with the LAL-assay. Mixed
      effects models were used to investigate possible determinants of exposure.
      Simultaneous parallel filter samples, impinger samples and viable total bacteria
      and Gram-negative bacterial samples were taken to compare analytical techniques.
      Filter and impinger samples were analyzed with the LAL-assay, gas chromatography
      mass spectrometry (GC-MS) and fluorescence microscopy. RESULTS: Endotoxin
      exposure levels were moderate to low (geometric mean personal exposure 27
      EU/m(3), stationary 33 EU/m(3), task-based 64 EU/m(3)), yet differences between
      jobs and sources and some determinants of exposure were identified. Exposure
      varied more from day to day than between workers. Concentrations in filter
      samples were higher and more consistent than in impinger samples. Fungi and Gram
      positive bacteria were found in higher levels than Gram-negative bacteria. The
      LAL assay and GC-MS showed comparable endotoxin levels. DISCUSSION AND
      CONCLUSION: Endotoxin exposure in Dutch sewage treatment workers was relatively
      low. Comparison of sampling and analytical techniques suggests that the LAL-assay
      did not result in much exposure misclassification. It thus seems justified to
      perform filter measurements in combination with the LAL-assay to measure
      endotoxin exposure in sewage treatment plants.

PMID- 19118447
TI  - Nothing to spit at: the salivary proteome of type 2 diabetes.

PMID- 19118449
TI  - Imaging-based live cell yeast screen identifies novel factors involved in
      peroxisome assembly.
AB  - We describe an imaging-based method in intact cells to systematically screen
      yeast mutant libraries for abnormal morphology and distribution of fluorescently
      labeled subcellular structures. In this study, chromosomally expressed green
      fluorescent protein (GFP) fused to the peroxisomal targeting sequence 1,
      consisting of serine-lysine-leucine, was introduced into 4740 viable yeast
      deletion mutants using a modified synthetic genetic array (SGA) technology. A
      benchtop robot was used to create ordered high-density arrays of GFP-expressing
      yeast mutants on solid media plates. Immobilized live yeast colonies were
      subjected to high-resolution, multidimensional confocal imaging. A software tool
      was designed for automated processing and quantitative analysis of acquired
      multichannel three-dimensional image data. The study resulted in the
      identification of two novel proteins, as well as of all previously known proteins
      required for import of proteins bearing peroxisomal targeting signal PTS1, into
      yeast peroxisomes. The modular method enables reliable microscopic analysis of
      live yeast mutant libraries in a universally applicable format on standard
      microscope slides, and provides a step toward fully automated high-resolution
      imaging of intact yeast cells.

PMID- 19118450
TI  - Temporal quantitative proteomics by iTRAQ 2D-LC-MS/MS and corresponding mRNA
      expression analysis identify post-transcriptional modulation of actin
      cytoskeleton regulators during TGF-beta-Induced epithelial-mesenchymal
      transition.
AB  - To gain insights into how TGF-beta regulates epithelial-mesenchymal transition
      (EMT), we assessed the time course of proteins and mRNAs during EMT by multiplex
      iTRAQ labeling and 2D-LC-MS/MS, and by hybridization, respectively. Temporal
      iTRAQ analysis identified 66 proteins as differentially expressed during EMT,
      including newly associated proteins calpain, fascin and macrophage-migration
      inhibitory factor (MIF). Comparing protein and mRNA expression overtime showed
      that all the 14 up-regulated proteins involved in the actin-cytoskeleton
      remodeling were accompanied by increases in corresponding mRNA expression.
      Interestingly, siRNA mediated knockdown of cofilin1 potentiated TGF-beta-induced
      EMT. Further analysis of cofilin1 and beta-actin revealed an increase in their
      mRNA stability in response to TGF-beta, contributing to the observed increase in
      mRNA and protein expression. These results are the first demonstration of post
      transcriptional regulation of cytoskeletal remodelling and a key role for
      cofilin1 during TGF-beta-induced EMT.

PMID- 19118451
TI  - Comparative temporal proteomics of a response regulator (SO2426)-deficient strain
      and wild-type Shewanella oneidensis MR-1 during chromate transformation.
AB  - Predicted orphan response regulators encoded in the Shewanella oneidensis MR-1
      genome are poorly understood from a cellular function perspective. Our previous
      transcriptomic and proteomic analyses demonstrated that an annotated DNA-binding
      response regulator, SO2426, was significantly up-regulated in wild-type S.
      oneidensis cells at both the mRNA and protein levels in response to acute
      chromate [Cr(VI)] challenge, suggesting a potential regulatory role for this
      protein in metal stress pathways. To investigate the impact of SO2426 activity on
      chromate stress response at a genome-wide scale, we describe here comparative and
      temporal proteome characterizations using multidimensional HPLC-MS/MS and
      statistical analysis to identify differentially expressed proteins in biological
      replicates of wild-type S. oneidensis MR-1 and a so2426 deletion (Deltaso2426)
      strain, which exhibited an impaired Cr(VI) transformation rate compared to that
      of the parental strain. Global protein profiles were examined at different time
      intervals (0, 1, 3, 4 h) following exogenous chromate challenge. Results
      indicated that deletion of the so2426 gene negatively affected expression of a
      small protein subset (27 proteins) including those with annotated functions in
      siderophore biosynthesis (SO3032), Fe uptake (SO4743), intracellular Fe storage
      (Bfr1), and other transport processes. Cr(VI) exposure and subsequent
      transformation dramatically increased the number of differentially expressed
      proteins detected, with up-regulated abundance patterns observed largely for
      proteins involved in general stress protection and detoxification strategies,
      cell motility, and protein fate. In addition, the proteome data sets were mined
      for amino acids with potential post-translational modifications (PTMs) indicative
      of a level of gene expression regulation extending beyond the transcriptional
      control imposed by SO2426.

PMID- 19118452
TI  - Proteomic identification of salivary biomarkers of type-2 diabetes.
AB  - The identification of biomarkers to noninvasively detect prediabetes/diabetes
      will facilitate interventions designed to prevent or delay progression to frank
      diabetes and its attendant complications. The purpose of this study was to
      characterize the human salivary proteome in type-2 diabetes to identify potential
      biomarkers of diabetes. Whole saliva from control and type-2 diabetic individuals
      was characterized by multidimensional liquid chromatography/tandem mass
      spectrometry (2D-LC-MS/MS). Label-free quantification was used to identify
      differentially abundant protein biomarkers. Selected potential biomarkers were
      then independently validated in saliva from control, diabetic, and prediabetic
      subjects by Western immunoblotting and ELISA. Characterization of the salivary
      proteome identified a total of 487 unique proteins. Approximately 33% of these
      have not been previously reported in human saliva. Of these, 65 demonstrated a
      greater than 2-fold difference in abundance between control and type-2 diabetes
      samples. A majority of the differentially abundant proteins belong to pathways
      regulating metabolism and immune response. Independent validation of a subset of
      potential biomarkers utilizing immunodetection confirmed their differential
      expression in type-2 diabetes, and analysis of prediabetic samples demonstrated a
      trend of relative increase in their abundance with progression from the
      prediabetic to the diabetic state. This comprehensive proteomic analysis of the
      human salivary proteome in type-2 diabetes provides the first global view of
      potential mechanisms perturbed in diabetic saliva and their utility in detection
      and monitoring of diabetes. Further characterization of these markers in a larger
      cohort of subjects may provide the basis for new, noninvasive tests for diabetes
      screening, detection, and monitoring.

PMID- 19118453
TI  - First Archaeal PEPB-Serine Protease Inhibitor from Sulfolobus solfataricus with
      Noncanonical Amino Acid Sequence in the Reactive-Site Loop.
AB  - The specific inhibition of serine proteinases, which are crucial switches in many
      important physiological processes, is of great value both for basic research and
      for therapeutic applications. In this study, we report the molecular cloning of
      the sso0767 gene from Sulfolobus solfataricus, and the functional
      characterization of its product, SsCEI, which represents the first archaeal
      phosphatidylethanolamine-binding protein (PEBP)-serine proteinase inhibitor,
      reported to date. SsCEI is a monomer protein with a molecular mass of 19.0 kDa
      and a pI of 6.7, which is able to inhibit the serine proteases alpha-chymotrypsin
      and elastase with K(i) values of 0.08 and 0.1 microM, respectively. Moreover
      SsCEI is extremely resistant to both thermal inactivation and proteolytic attack
      suggesting compact folding of the protein. Within the I51 family, the archaeal
      inhibitor shows strong similarity to the human and murine members. The three
      dimensional model of SsCEI revealed a general beta-fold and the presence of an
      anion-binding pocket, the hallmark of the PEBP family. Moreover SsCEI binds the
      cognate proteases according to a common, substrate-like standard mechanism. Point
      mutation experiments supported the prediction of the protease-binding site
      located on the surface at the C- terminal region of the protein. Interestingly,
      searches based on preidentified structural reactive loop motifs revealed the
      occurrence of a sequence (T123-N130) that is not represented in all serine
      protease inhibitor families. This unique motif may provide new insights into both
      the inhibitor/protease binding mode and the specific biological functions of
      SsCEI within the PEBP family.

PMID- 19118455
TI  - The nitrone free radical scavenger NXY-059 is neuroprotective when administered
      after traumatic brain injury in the rat.
AB  - Reactive oxygen species (ROS) are important contributors to the secondary injury
      cascade following traumatic brain injury (TBI), and ROS inhibition has
      consistently been shown to be neuroprotective following experimental TBI. NXY
      059, a nitrone free radical trapping compound, has been shown to be
      neuroprotective in models of ischemic stroke but has not been evaluated in
      experimental TBI. In the present study, a continuous 24-h intravenous infusion of
      NXY-059 or vehicle was initiated 30 min following a severe lateral fluid
      percussion brain injury (FPI) in adult rats (n=22), and histological and
      behavioral outcomes were evaluated. Sham-injured animals (n=22) receiving
      identical drug infusion were used as controls. Visuospatial learning was
      evaluated in the Morris water maze at post-injury days 11-14, followed by a probe
      trial (memory test) at day 18. The animals were sacrificed at day 18, and loss of
      hemispheric brain tissue was measured in microtubule-associated protein (MAP)-2
      stained sections. Brain-injured, NXY-059-treated animals showed a significant
      reduction of visuospatial learning deficits when compared to the brain-injured,
      vehicle-treated control animals (p < 0.05). NXY-059-treated animals significantly
      reduced the loss of hemispheric tissue compared to brain-injured controls (43.0
      +/- 11 mm3 versus 74.4 +/- 19 mm3, respectively; p < 0.01). The results show that
      post-injury treatment with NXY-059 significantly attenuated the loss of injured
      brain tissue and improved cognitive outcome, suggesting a major role for ROS in
      the pathophysiology of TBI.

PMID- 19118454
TI  - Improvements in orthostatic instability with stand locomotor training in
      individuals with spinal cord injury.
AB  - Prospective assessment of cardiovascular control in individuals with spinal cord
      injury (SCI) in response to active stand training. Cardiovascular parameters were
      measured at rest and in response to orthostatic challenge before and after
      training in individuals with clinically complete SCI. The goal of this study was
      to evaluate the effect of active stand training on arterial blood pressure and
      heart rate and changes in response to orthostatic stress in individuals with SCI.
      Measurements were obtained in individuals with SCI (n=8) prior to and after 40
      and 80 sessions of the standing component of a locomotor training intervention
      (stand LT). During standing, all participants wore a harness and were suspended
      by an overhead, pneumatic body weight support (BWS) system over a treadmill.
      Trainers provided manual facilitation as necessary at the trunk and legs. All
      individuals were able to bear more weight on their legs after the stand LT
      training. Resting arterial blood pressure significantly increased in individuals
      with cervical SCI after 80 training sessions. At the end of the training period,
      resting systolic blood pressure (BP) in individuals with cervical SCI in a seated
      position, increased by 24% (from 84 +/- 5 to 104 +/- 7 mmHg). Furthermore,
      orthostatic hypotension present in response to standing prior to training
      (decrease in systolic BP of 24 +/- 14 mmHg) was not evident (decrease in systolic
      BP of 0 +/- 11 mmHg) after 80 sessions of stand LT. Hemodynamic parameters of
      individuals with thoracic SCI were relatively stable prior to training and not
      significantly different after 80 sessions of stand LT. Improvements in resting
      arterial blood pressure and responses to orthostatic stress in individuals with
      clinically complete cervical SCI occurred following intensive stand LT training.
      These results may be attributed to repetitive neuromuscular activation of the
      legs from loading and/or conditioning of cardiovascular responses from
      repetitively assuming an upright posture.

PMID- 19118456
TI  - Role of vasopressin V(1a) and V2 receptors for the development of secondary brain
      damage after traumatic brain injury in mice.
AB  - Brain edema is still one of the most deleterious sequels of traumatic brain
      injury (TBI), and its pathophysiology is not sufficiently understood. The goal of
      the current study was to investigate the role of arginine vasopressin (AVP), also
      known as antidiuretic hormone (ADH), an important regulator of tissue water
      homeostasis, for the formation of post-traumatic brain edema, intracranial
      pressure (ICP), brain damage, and functional deficits following brain trauma.
      C57/B16 mice (n=112) were subjected to controlled cortical impact (CCI; 8m/s, 1
      mm). At 3 min after trauma, animals received 500 ng of the AVP V(1a)-receptor
      antogonist (deamino-Pen(1), O-Me-Tyr(2), Arg(8)]-Vasopressin) or 500 ng of the
      AVP V2-receptor antagonist (adamantaneacetyl(1), O-Et-D-Tyr(2),Val(4),
      Abu(6),Arg(8,9)]-Vasopressin) by intracerebroventricular injection. After trauma,
      cerebral water content (24 h), ICP (24 h), contusion volume (24 h and 7 days),
      and functional outcome (1-7 days) were assessed (n=8 per experimental group).
      Post-traumatic inhibition of AVP V(1A) receptors reduced ICP by 29% (p < 0.05),
      brain water content by 45% (p < 0.05), and secondary contusion expansion by 37%
      (p < 0.05), and it significantly improved motor function 6 and 7 days after
      trauma (p < 0.05). Inhibition of AVP V2 receptors had no significant effect. The
      current results demonstrate that vasopressin V(1A) receptors are involved in the
      pathogenesis of brain edema formation and the subsequent development of secondary
      brain damage after traumatic brain injury. Accordingly, our study suggests that
      vasopressin V(1A) receptors may represent a novel therapeutic target for the
      treatment of post-traumatic brain edema and secondary brain damage.

PMID- 19118457
TI  - Hypermetabolism following moderate to severe traumatic acute brain injury: a
      systematic review.
AB  - Elevations of metabolic rate following traumatic brain injury (TBI) have been
      reported previously, with estimates ranging from 32% to 200% above normal values.
      The aim of this systematic review was to describe the pattern of energy
      expenditure during the first 30 days following TBI. We searched six databases for
      trials that measured the energy expenditure at least once during the first 30
      days post-injury and compared that value to one that would be predicted in the
      non-injured state. We identified 24 studies, three of which were randomized
      controlled trials (RCTs). The sample sizes of the included studies ranged from 6
      to 80 (mean, 24.7), and the mean Glasgow Coma Scale (GCS) score of subjects was
      4.8. Mean energy expenditure, expressed as a percentage of a predicted value,
      ranged from 75% to 200%. The lowest values were reported in patients admitted in
      brain death. Several factors were found to have modulating effects on energy
      expenditure. The administration of paralyzing agents, sedatives, or barbiturates
      reduced metabolic rate by approximately 12-32%. Propranolol and morphine were
      associated with smaller decreases in energy expenditure. Factors that do not
      appear to augment the hypermetabolic response included the administration of
      steroids and method of feeding (enteral vs. parenteral). Based on our results, it
      was unclear if elevated temperature, the presence of extracranial injury, or the
      severity of injury further exacerbate hypermetabolism. We conclude that energy
      expenditure following TBI is highly variable, and the use of standard factors to
      estimate the energy needs of individual patients are inappropriate and should be
      discouraged.

PMID- 19118458
TI  - A transition to laparoendoscopic single-site surgery (LESS) radical
      prostatectomy: human cadaver experimental and initial clinical experience.
AB  - BACKGROUND AND PURPOSE: Laparoendoscopic single-site surgery (LESS) represents a
      novel approach to abdominal surgery. Several applications have already been
      described. Drawbacks include limited range of motion and need for articulated
      instruments. Robotic technology could overcome such technical difficulties. We
      report our experience with LESS radical prostatectomy (LESS-RP) in a cadaver and
      LESS robot-assisted radical prostatectomy (LESS-RARP) in a human patient.
      MATERIAL AND METHODS: Standard laparoscopic instruments (SLI) and articulated
      laparoscopic instruments were used in the cadaveric LESS-RP. The da Vinci system
      was used in the LESS-RARP. Both procedures reproduced standard extraperitoneal
      laparoscopic prostatectomy as performed at Institut Montsouris. Control of the
      dorsal venous complex (DVC) and urethrovesical anastomosis (UVA) were key
      elements evaluated for feasibility. RESULTS: Cadaveric model: Total operative
      time (TOT) was 160 minutes, with 5 minutes for the DVC (one stitch) and 35
      minutes for the UVA (six stitches). Although articulated instruments were helpful
      in the operation, SLI remained essential for the procedure. Clinical experience:
      LESS-RARP was performed for T(1c) prostate cancer. TOT was 150 minutes, including
      5 minutes for the DVC (one figure-of-eight stitch) and 30 minutes for the UVA
      (six interrupted stitches). Blood loss was 500 mL. Bilateral neurovascular
      preservation was performed, and results of final pathologic examination showed
      negative surgical margins. CONCLUSIONS: The human cadaver is an adequate model
      for LESS-RP, and LESS-RARP is feasible to be performed in the clinical arena. The
      synergy of robotic technology and LESS represents a new generation of surgery.

PMID- 19118459
TI  - Measuring stone surface area from a radiographic image is accurate and
      reproducible with the help of an imaging program.
AB  - BACKGROUND AND PURPOSE: The surface area of the stone from a radiographic image
      is one of the more suitable parameters defining stone bulk. The widely accepted
      method of measuring stone surface area is to count the number of square
      millimeters enclosed within a tracing of the stone outline on graph paper. This
      method is time consuming and cumbersome with potential for human error,
      especially when multiple measurements are needed. The purpose of this study was
      to evaluate the accuracy, efficiency, and reproducibility of a commercially
      available imaging program, Adobe Photoshop 7.0 for the measurement of stone
      surface area. MATERIALS AND METHODS: The instructions to calculate area using the
      software are simple and easy in a Windows-based format. The accuracy of the
      imaging software was estimated by measuring surface areas of shapes of known
      mathematical areas. The efficiency and reproducibility were then evaluated from
      radiographs of 20 persons with radiopaque upper-tract urinary stones. The surface
      areas of stone images were measured using both graph paper and imaging software.
      Measurements were repeated after 10 days to assess the reproducibility of the
      techniques. The time taken to measure the area by the two methods was also
      assessed separately. RESULTS: The accuracy of the imaging software was estimated
      to be 98.7%. The correlation coefficient between the two methods was R(2) = 0.97.
      The mean percentage variation using the imaging software was 0.68%, while it was
      6.36% with the graph paper. The mean time taken to measure using the image
      analyzer and graph paper was 1.9 +/- 0.8 minutes and 4.5 +/- 1.08 minutes,
      respectively (P < 0.001) CONCLUSION: The imaging program is accurate, fast, and
      highly reproducible in estimating two-dimensional stone surface area from
      radiographs compared with manual measurements using graph paper.

PMID- 19118460
TI  - Foley catheter characteristics: predicting problems.
AB  - PURPOSE: To evaluate the physical properties of urethral catheters that are
      predictive of ease of placement and risk of urethral trauma: Stiffness, buckling,
      and friction forces. MATERIALS AND METHODS: Eleven Bard Lubri-Sil and 10 Kendall
      Dover 16F Foley catheters were tested using a linear motion stage driven by a
      stepper motor with a resolution of 5 microns/step or by hand. Force was measured
      at a sampling rate of 5 Hz with a Wagner FDIX digital force gauge. Friction force
      was measured by pulling each Foley catheter at a rate of 2.5 mm/s through a 15.6F
      hole drilled in 36-mm thick biologic material (Oscar Meyer Beef Light bologna 12
      oz package). Ease of advancement was measured by the force necessary to maneuver
      a catheter around a 90-degree turn in a bulbar urethra modeled by 5/16 inch inner
      diameter silicone tubing and lubricant. Buckling forces were measured at the tip
      (8 mm), from the distal end of the balloon to the tip (30 mm), and along a 20 cm
      section of the shaft using the appropriate size force gauge. RESULTS: No
      significant difference was noted for friction force. The Kendall catheters
      (0.0686 +/- 0.102 lb(f)) took more force to advance around a 90-degree turn,
      compared with the Bard (0.602 +/- 0.110 lb(f), P = 0.003). Buckling force along
      the shaft and from the balloon to the tip was significantly greater for the Bard
      (0.051 +/- 0.02 lb(f), P < 0.001 and 0.892 +/- 0.166 lb(f), P < 0.001) compared
      with the Kendall (0.027 +/- 0.007 lb(f) and 0.803 +/- 0.129 lb(f)) catheters.
      Stiffness of the tip was significantly greater for the Kendall (2.644 +/- 0.552
      lb(f), P < 0.001) compared with the Bard (2.101 +/- 0.437 lb(f)) Foley catheters.
      CONCLUSIONS: Traumatic catheterization is a major cause of urethral stricture.
      Catheter stiffness may increase the risk of urethral injury and subsequent
      stricture formation. Ease of advancement and tip stiffness may be important at
      predicting clinical performance of urethral catheters.

PMID- 19118461
TI  - Nephron-sparing diagnosis and management of renal keratinizing desquamative
      squamous metaplasia.
AB  - BACKGROUND AND PURPOSE: Keratinizing desquamative squamous metaplasia (KDSM) of
      the upper urinary tract is a rare condition for which there is no defined
      management plan. A condition historically treated with extirpative surgery,
      conservative management would be preferable, because this is almost certainly a
      benign condition. We report the favorable clinical course of two cases of renal
      KDSM diagnosed and managed with a nephron-sparing approach, relying on
      ureteroscopy and serial imaging. PATIENTS AND METHODS: Retrospective chart review
      was performed to obtain history, physical examination results, radiographic
      imaging, and diagnostic procedures. RESULTS: Both patients were referred to our
      institution for evaluation of complex cystic renal masses. Both reported passing
      flaky material in their urine. Flexible ureteroscopy revealed waxy sediment in
      the collecting system, which broke up easily with manipulation and proved to be
      squamous keratin debris on cytologic and histologic examination. In 1 patient, we
      obtained a percutaneous needle biopsy as well, which revealed benign keratinizing
      squamous epithelium. All findings were consistent with KDSM. Each patient has
      since been followed conservatively with CT. In 1 case, there has been slight
      growth of the mass but no worrisome changes after 42 months. In the other case,
      there were several new renal collecting system filling defects on CT 17 months
      after diagnosis. Another ureteroscopy revealed the same findings as the original,
      with the addition of keratin debris draining out of the lesion into the rest of
      the kidney. CONCLUSIONS: Our two cases of KDSM confirm the feasibility of nephron
      sparing management using a combination of diagnostic ureteroscopy and imaging
      surveillance. The duration of follow-up without adverse events suggests that the
      finding of renal KDSM is not necessarily an indication for extirpative surgery,
      and that conservative management is an appropriate option.

PMID- 19118462
TI  - Robot-assisted ureterectomy and ureteral reconstruction for urothelial carcinoma.
AB  - BACKGROUND AND PURPOSE: Urothelial carcinoma of the distal ureter can be managed
      by ureterectomy followed by reconstruction of the urinary system. We review our
      experience with robot-assisted ureterectomy. PATIENTS AND METHODS: Nine
      consecutive patients who were candidates for ureterectomy underwent robot
      assisted surgery between 7/8/2005 and 7/25/2006. Patient characteristics,
      intraoperative parameters, and short-term outcomes were retrospectively reviewed.
      RESULTS: Mean operative time was 252 minutes. The mean blood loss was 44 mL, and
      no patient needed a transfusion. The mean hospital stay was 1.5 days. Six
      patients needed a psoas hitch; one patient each underwent a primary ureteral
      anastomosis, a direct ureteral reimplant into the dome of the bladder, and distal
      ureterectomy for tumor in a ureteral stump after nephrectomy. The ureteral
      reimplant was performed intravesically in one patient and extravesically in five
      patients. A bladder cuff was excised in all patients who were undergoing a distal
      ureterectomy. All surgical margins were negative, and five patients had high
      grade tumor. A ureteral stricture developed in one patient, and a patient
      experienced aspiration pneumonia in the postoperative period. CONCLUSIONS: Robot
      assisted ureterectomy and ureteral reconstruction is safe and feasible, and
      offers patients the advantages of minimally invasive surgery. Future studies with
      additional patients and longer follow-up will determine the oncologic
      effectiveness of this procedure.

PMID- 19118463
TI  - Laparoscopic pyeloplasty using the postanastomotic dismemberment method:
      technique and results.
AB  - BACKGROUND AND PURPOSE: Despite excellent results, widespread acceptance of the
      laparoscopic dismembered Anderson-Hynes pyeloplasty (AH) is hampered by its steep
      learning curve. Laparoscopic nondismembered pyeloplasty techniques, although
      simpler, have not matched the results of AH. We have been using a technical
      modification of AH to combine its excellent outcome with technical ease of
      nondismembered pyeloplasties. We describe the procedure and results of
      laparoscopic postanastomotic dismemberment (PAD) pyeloplasty for primary
      ureteropelvic junction (UPJ) obstruction. PATIENTS AND METHODS: PAD technique
      involves an initial partial division of the dilated pelvis and ureteral
      spatulation without dismembering the UPJ. Both layers of ureteropelvic
      anastomosis are completed before dismemberment and pelvic reduction. Forty-one
      PAD procedures in 40 patients with UPJ obstruction and follow-up of at least 3
      months were evaluated. Mean age was 37.2 years (range 2-82 years) with 22
      patients younger than 15 years. The UPJ was dependent in 31 and had high
      insertion in 10 (24.4%). The stenotic segment was long (> or =1.5 cm) in 18
      (43.9%). Crossing vessels and secondary calculi were observed in six (14.6%) and
      seven (17.1%) units. RESULTS: Mean (+/- SD) blood loss, hospital stay,
      convalescence, and analgesia requirement were 68.1 +/- 37.6 mL, 3.8 +/- 1.1 days,
      11.4 +/- 3.9 days, and 204.8 +/- 60.5 mg diclofenac, respectively. The mean
      operative time was 97.6 +/- 22.1 minutes. There was one intraoperative
      complication in the form of injury to a renal vein tributary, with no
      transfusions or conversions. Postoperative complications included pain after
      stent removal, persistent drainage, and pyelonephritis in 1, 2, and 4 patients,
      respectively. Mean follow-up was 19.5 months (range 3-58 months), with a success
      rate of 95.1%. Failures were not attributable to UPJ configuration, length of
      stenosis, or age. CONCLUSIONS: The PAD technique has several practical advantages
      with a shorter operative time compared with other historical series of
      laparoscopic pyeloplasty (LP). It combines the ease of nondismembered LP with the
      excellent outcome of dismembered techniques.

PMID- 19118464
TI  - Laparoscopic radical nephrectomy for very large renal tumors (> or =10 cm): is
      there a size limit?
AB  - BACKGROUND AND PURPOSE: The role of laparoscopic radical nephrectomy (LRN) for
      very large renal tumors remains to be defined. We review our experience with LRN
      for very large (> or =10 cm) renal malignancies. PATIENTS AND METHODS: A
      retrospective analysis of 360 consecutive patients who underwent LRN for renal
      tumors between October 1999 and May 2007 in a tertiary academic center identified
      11 patients with malignancies > or =10 cm. RESULTS: Median age was 67 years
      (range 48-80 y), operative time was 170 minutes (range 80-240 min), estimated
      blood loss was 150 mL (range 50-300 mL), and length of stay was 2 days (range 1-6
      d). There were two minor postoperative complications (acute renal insufficiency
      and ileus). Median tumor size was 12 cm (range 10-21 cm). Pathologic stage for
      patients with renal cell carcinoma was T(2), T(3a), T(3b), and T(4), in five,
      three, two, and one patient(s), respectively. One patient died after brain
      metastasis developed. Two patients in whom pulmonary metastases developed were
      still alive at last follow-up. CONCLUSIONS: LRN was successfully performed in
      patients with renal tumors up to 21 cm. Important considerations when performing
      LRN include the individual clinical picture, surgeon experience, tumor location,
      and patient well-being. LRN for very large tumors is feasible in properly
      selected patients and can have significant benefits in the palliative setting.

PMID- 19118465
TI  - Health-related quality of life in I-125 prostate brachytherapy patients treated
      with and without volume-reducing hormone therapy: results of a short-term
      prospective study.
AB  - PURPOSE: This study describes the differences in short-term effects of health
      related quality of life (HRQOL) in I-125 prostate brachytherapy patients who were
      treated with and without volume-reducing hormone therapy. PATIENTS AND METHODS:
      Prostate cancer patients (N = 312) filled out questionnaires on HRQOL (European
      Organization of Research and Treatment of Cancer Quality of Life Questionnaire
      [EORTC-QLQ]-C30 and EORTC-QLQ-PR25) before treatment and 6 weeks and 3 months
      after treatment. HRQOL was compared between the two groups: Patients who were
      receiving brachytherapy (n = 233) and patients who were receiving brachytherapy
      with volume-reducing hormone therapy (n = 79). Duration of androgen ablation was
      9 months, starting 3 months before I-125 implantation. RESULTS: After treatment,
      patients reported significant and clinically relevant decreased scores on the
      following subscales: Global health status, role functioning, social functioning,
      pain, insomnia, bowel symptoms and functioning, and treatment-related functions,
      regardless of the therapy they received. Results showed that prostate cancer
      patients receiving brachytherapy with volume-reducing hormone therapy also
      experienced lower treatment-related functions and lower sexual function.
      Significant time by treatment interaction effects were found for treatment
      related functions. The subscale treatment-related functions was the only scale
      that showed a difference over time, between treatments, and time by treatment.
      CONCLUSIONS: The differences in HRQOL between brachytherapy and brachytherapy
      with volume-reducing hormone therapy are small; they both decrease HRQOL and
      increase treatment-related problems. A long-term prospective study on long-term
      effects on HRQOL is needed to obtain a more comprehensive view of the
      consequences of a specific treatment modality over time. Our results can help to
      identify the problems patients face after brachytherapy with or without hormone
      therapy; these problems deserve additional attention during the period of
      recovery.

PMID- 19118466
TI  - Double-j stenting compared with one night externalized ureteral catheter
      placement in tubeless percutaneous nephrolithotomy.
AB  - PURPOSE: We prospectively analyzed the outcome of tubeless percutaneous
      nephrolithotomies (PCNLs) using two different stenting techniques (i.e.,
      externalized ureteral catheter compared with Double-J placement) without strict
      exclusion or inclusion criteria. PATIENTS AND METHODS: Forty-six patients who
      were undergoing tubeless PCNL were randomized to two groups: Group 1 (tubeless
      PCNL with externalized ureteral catheter) and group 2 (tubeless PCNL with Double
      J placement). The only exclusion criterion was presence of significant residual
      stones. The two groups were comparable with regard to age, sex, stone laterality,
      stone burden, and number of previous open renal surgeries. Factors evaluated
      included operative time, stent-related symptoms, analgesic requirement,
      postoperative pain, postoperative morbidity, hospital stay, blood loss, and
      success rates. RESULTS: The mean operative times, mean number of accesses,
      percentage of supracostal accesses, mean visual analog scale scores, analgesic
      requirements, mean decreases in hemoglobin level, blood transfusion rates,
      success rates, and mean hospital stays were not statistically significant in both
      groups. The only statistically significant difference between groups was the
      postoperative stent-related symptoms. In group 2, 52.1% experienced some sort of
      stent-related symptoms. In most of the patients, these symptoms were not severe;
      however, in two of them (16.6 %), oral medication therapy with anticholinergics
      was needed. None of the patients in group 1 had stent-related symptoms and needed
      medication (P < 0.01). CONCLUSIONS: Tubeless PCNL with externalized ureteral
      catheter is as feasible as Double-J stenting. Moreover, stent-related discomforts
      because of the presence of a Double-J stent and the need for postoperative
      cystoscopy to remove the Double-J stent can be avoided with an externalized
      ureteral catheter.

PMID- 19118467
TI  - Case report: percutaneous catheter management of persistent urine leak due to
      iatrogenic infundibular stenosis after partial nephrectomy.
AB  - We describe two cases of persistent urine leak after partial nephrectomies that
      were both due to surgically induced isolated calices. We hypothesize that the
      isolated calices were created while suturing the collecting systems, with
      inadvertent closure of single infundibula. Both cases were managed by
      percutaneous nephrostomy tube drainage of the renal pelvises and the isolated
      calices, in addition to indwelling ureteral stents. This novel management
      technique has not been described in the literature and served as an effective
      management tool for this rare complication after partial nephrectomy.

PMID- 19118468
TI  - Laparoscopic management of potentially malignant or complex adrenal cysts abiding
      by the principles of surgical oncology.
AB  - BACKGROUND AND PURPOSE: Few articles have illustrated minimally invasive
      management of potentially malignant adrenal cysts. The aim of this study was to
      evaluate the feasibility of laparoscopic adrenalectomy for potentially malignant
      adrenal cysts. PATIENTS AND METHODS: Eight patients with potentially malignant or
      complex cysts were treated by laparoscopic adrenalectomy in the past 10 years at
      our institution. The operative techniques strictly abided by the principles of
      surgical oncology. The entire adrenal gland, including the cyst, was excised en
      bloc via a lateral transperitoneal laparoscopic approach and moved into a LapSac
      bag. After protecting the exterior abdominal surface, we pulled the LapSac's
      opening out of the periumbilical wound and opened the cyst wall to siphon all the
      fluid content with a sucker tip dipped into the cyst cavity. Then the remaining
      cyst components and the adrenal gland were removed with the bag. RESULTS: All of
      the laparoscopic operations were successful without intraoperative or
      postoperative morbidity, open conversion, or mortality. Mean operative time was
      135 minutes with minimal blood loss. Mean hospital stay was 3.4 days.
      Histopathologic examinations revealed five hemorrhagic pseudocysts, two
      endothelial cysts, and a cystic pheochromocytoma. There was involvement of
      periadrenal adipose tissues by the chromium-staining tumor cells in the cystic
      pheochromocytoma, and malignancy could not be excluded. At a mean follow-up of 40
      months, all patients were asymptomatic and had no radiographic evidence of
      recurrence or dissemination. CONCLUSIONS: To our knowledge, this report
      represents the largest series of laparoscopic excisions for complex adrenal
      cysts. This technique is safe and feasible, while maintaining the benefits of
      minimal invasiveness.

PMID- 19118470
TI  - Dynamics of charging of muscovite mica: measurement and modeling.
AB  - The advent of a new method for measuring the zeta potential of planar surfaces,
      the rotating disk, allowed the investigation of the charging process of mica
      after immersion in water. The zeta potential of freshly cleaved muscovite mica
      was recorded within seconds of immersion of the sample and in fractions of a
      second thereafter. The zeta potential of mica in water at pH = 5.6 with no added
      potassium changed by 40-50 mV over approximately 1 min. A model of adsorption and
      desorption of potassium ions and protons captured this behavior and provided a
      framework for determination of surface adsorption rate constants. The charging of
      mica in alkaline KCl solutions of arbitrary concentration, however, was too fast
      for observation. The equilibrium zeta potential depended on the logarithm of salt
      concentration, in agreement with a model based on ion exchange reactions. The
      average values of the proton adsorption, proton desorption, potassium adsorption,
      and potassium desorption rate coefficients were 45 L/s +/- 15, 0.0014/s +/-
      0.0006, 58 L/s +/- 5, and 0.14/s +/- 0.03, respectively. An equation giving the
      zeta potential as a function of the rate parameters and the concentrations of
      potassium ions and protons was derived. It is demonstrated that subtraction of
      zeta potentials, measured at different solution compositions within the same
      experiment, eliminates extrinsic factors and brings data from disparate
      measurements into agreement.

PMID- 19118469
TI  - Competitive adsorption of glycine and water on the fluorapatite (100) surface.
AB  - The atomic structure of the aqueous glycine-fluorapatite (100) interface was
      investigated using grazing incidence X-ray diffraction. Experimental data
      analysis of crystal truncation rod intensities revealed detailed information on
      lateral as well as perpendicular ordering of the adsorbate molecules and the
      nature of atomic relaxations in the fluorapatite (FAp) (100) surface. Glycine and
      water molecules are arranged in two periodically ordered layers at the aqueous
      glycine-mineral interface. The adsorption process on the mineral surface is site
      competitive as both the glycine and water molecules show equal affinity toward
      surface Ca2+ cations. The glycine molecules interact directly with the FAp (100)
      surface, where one of their carboxylate groups coordinates with the surface Ca2+
      cations. From the surface structure refinement, atomic positions of one glycine
      and four water molecules per unit cell were determined, along with the atomic
      relaxations in the FAp (100) surface. Molecular dynamic simulations were used to
      determine the long-range order of the adsorbate layers by investigating the
      hydrogen bonds.

PMID- 19118471
TI  - Percutaneous nephrolithotripsy in patients with diabetes mellitus.
AB  - PURPOSE: To compare the surgical outcomes in a cohort of patients with diabetes
      who were undergoing percutaneous nephrolithotripsy (PCNL) for renal stone disease
      to a nondiabetic group of patients at a single center. PATIENTS AND METHODS:
      Between July 1990 and December 2005, all patients scheduled for PCNL were
      prospectively included in a single-center database. Preoperative, intraoperative,
      and postoperative data were prospectively collected and analyzed. Primary
      outcomes evaluated were stone-free rates and complications, including the need
      for blood transfusion, while the secondary outcome was length of hospital stay.
      This report specifically reviews these outcomes in patients known to have
      diabetes at the time of surgery. Both outcomes were compared with those obtained
      in our nondiabetic patient population. RESULTS: Analysis of the data from 183
      (13.7%) patients with diabetes of the 1338 patients undergoing PCNL revealed that
      patient age (63.1 years), surgical time (90.8 minutes), and complications (major
      2.2%), including need for transfusion (0.5%) and stone-free rate (94.5%), were
      not significantly different from those observed in our nondiabetic patients. The
      average length of hospital stay was significantly longer in the diabetic group
      (4.4 days vs 3.9 days, P = 0.022). Uric acid stone composition was found to be
      the most common stone composition among the patients with diabetes in this study
      (41%). CONCLUSIONS: PCNL can be performed with excellent stone-free rates and
      with an acceptable complication risk in the diabetic population. The incidence of
      uric acid stone disease appears to be significantly higher than previously
      reported and warrants heightened efforts directed toward stone prevention in this
      population.

PMID- 19118472
TI  - Peptides grafted from solids for the control of interfacial properties.
AB  - We have used solid-phase peptide synthesis to graft a peptide monolayer from a
      solid in order to modify the interfacial properties. We grafted a 15-residue
      peptide, EKEKEKEKEKEKEGG, containing a zwitterionic sequence of alternating
      lysine and glutamic acid residues from the surface of an aminosilanized silicon
      wafer by placing the silicon wafer within a commercial microwave peptide
      synthesizer. Such synthesizers are routinely used to make peptides on porous
      beads, but the peptides are subsequently cleaved and used independently of the
      solid support; our aim is to utilize the covalently bound peptide to control the
      surface properties without the need for cleavage and reattachment. We confirmed
      the presence of this peptide layer on the surface by X-ray photoelectron
      spectroscopy and ellipsometry. Atomic force microscopy was then used to study the
      forces between the peptide-modified surface and a borosilicate glass sphere as a
      function of the solution pH. The adsorbed peptide makes the silicon wafer pH
      responsive: at high pH the glass particle is repelled from the wafer, and at low
      pH it is attracted. Previous studies with synthetic polymers have shown that the
      "grafting from" method allows a much higher film density than "grafting to". We
      propose that the application of grafting from strategies to peptide layers may
      offer three additional benefits: (1) the film density can be controlled
      independently of the primary sequence of the peptide, (2) the sequence
      constraints for spontaneous adsorption are removed, and (3) the procedure is fast
      and efficient, which may lead to lower costs and the ability for high-throughput
      surface biofunctionalization. Moreover, peptide layers offer increased sequence
      diversity, control, and functionality compared to conventional polymer brushes.

PMID- 19118473
TI  - Gasless hand-assisted retroperitoneoscopic nephroureterectomy.
AB  - PURPOSE: To assess the efficacy of gasless hand-assisted retroperitoneoscopic
      nephroureterectomy (HARNU). PATIENTS AND METHODS: A total of 54 patients who
      underwent HARNU were enrolled in the study. Patients were divided into two
      groups: Retroperitoneoscopic nephroureterectomy with hand port (traditional
      HARNU) and without hand port (gasless HARNU). Each group was then divided further
      based on whether body mass index (BMI) value was greater or less than 24 kg/m(2).
      Operative times, blood loss, and hospital stay were recorded and compared between
      traditional HARNU and gasless HARNU groups by two-paired Student t test and
      Wilcoxon sign rank test. These results were also compared between different BMI
      groups. RESULTS: There were no open surgery conversions in this study. Only one
      patient needed repeated surgery because of urine leakage from the bladder cuff
      into the peritoneal space. No statistically significant differences existed in
      operative times, blood loss, and hospital stay between the hand port and no hand
      port groups in retroperitoneoscopic nephroureterectomy. Notably, no statistically
      significant differences existed regardless of whether BMI exceeded 24 kg/m(2) in
      each group. CONCLUSION: Gasless retroperitoneoscopic nephroureterectomy proved
      that the surgery can be performed without a hand port. Obesity did not cause an
      increase in operative time and blood loss in this study. Therefore, gasless
      retroperitoneoscopic nephroureterectomy is safe and provides the alternative
      choice for nephroureterectomy.

PMID- 19118474
TI  - Three metabolites from the mangrove endophytic fungus Sporothrix sp. (#4335) from
      the South China Sea.
AB  - Three metabolites, sporothrins A, B, and C (1-3), were isolated from the mangrove
      endophytic fungus Sporothrix sp. (#4335). Their structures were identified by the
      spectral data and X-ray diffractive techniques, with compound 1 showing strong
      inhibition of acetylcholine esterase. 1,3,6,8-Tetrahydroxynaphthalene (T4HN) was
      deduced as one of the precursors in the biosynthesis of 1 and 2. In a primary
      biosynthesis gene study, the partial gene fragment obtained with the LC1-Im/2c-Im
      primer pair was shown to be closely related to genes encoding T4HN synthase. The
      deduced protein sequences were highly homologous to the ketosynthase domains of
      other fungal PKS genes involved in T4HN biosynthesis.

PMID- 19118475
TI  - Management of renal masses with laparoscopic-guided radiofrequency ablation
      versus laparoscopic partial nephrectomy.
AB  - BACKGROUND AND PURPOSE: Laparoscopic-guided radiofrequency ablation (LRFA) has
      been introduced as a minimally invasive nephron-sparing management option for
      renal tumors. Many patients who desire treatment present with multiple
      comorbidities, which poses a therapeutic challenge. Our purpose is to determine
      if multipass LRFA is comparable, in terms of surgical risk and immediate
      postoperative outcomes, to laparoscopic partial nephrectomy (LPN). PATIENTS AND
      METHODS: A retrospective study identified 36 and 33 patients who underwent LRFA
      and LPN, respectively. Perioperative demographic data, tumor characteristics, and
      follow-up data were evaluated. Statistical analysis was performed using the
      Student t test and chi-square analysis. RESULTS: Age, American Society of
      Anesthesiology score, and Charlson Comorbidity Index were significantly higher in
      the LRFA group than the LPN group (P < 0.001). Average tumor size was 2.8 cm and
      3.1 cm for the LRFA and LPN groups, respectively. There were no significant
      differences in change between the preoperative and postoperative
      creatinine/glomerular filtration rate values or perioperative complication rates
      for the groups. Estimated blood loss and length of stay were significantly lower
      for the LRFA group than the LPN group (P < 0.05). Follow-up ranged 6 to 23 months
      and 6 to 58 months for the LRFA and the LPN groups, respectively. There has been
      no evidence of tumor recurrence in the follow-up period. CONCLUSIONS: We present
      our initial report comparing patients undergoing LRFA v LPN for the management of
      renal tumors. Our preliminary results with our experience with multipass
      laparoscopic-guided RFA demonstrate that this technique can be safely used in an
      elderly, higher risk population. Long-term follow-up is needed to determine
      oncologic efficacy.

PMID- 19118476
TI  - Aggregation of conjugated polymers in aromatic solvent.
AB  - Segments of conjugated polymers display the propensity to aggregate in solutions
      with common organic solvents. Here we revealed that the segmental aggregation of
      a conjugated polymer, poly(9,9-bis(2-ethylhexyl)fluorene-2,7-diyl), (PF2/6), in
      toluene was stabilized by the polymer-solvent complex formation through pi-pi
      stacking induction of solvent molecules and polymer segments. In this case, a
      portion of the solvent was trapped inside the aggregate domains upon bringing the
      system to the subambient temperatures. The residence time of these associated
      solvent molecules became long enough to yield a separate upfield-shifted NMR
      resonance. The line-shape of this resonance revealed alignment of the polymer
      segments in the aggregates. A portion of the solvent was frozen in the compact
      structure due to the formation of strong polymer-solvent complex.

PMID- 19118477
TI  - A general synthetic route to enantiopure 5-substituted cis-decahydroquinolines.
AB  - A practical synthetic route to enantiopure 5-substituted cis-decahydroquinolines
      has been developed, the key steps being a stereoselective cyclocondensation of 2
      substituted 6-oxocyclohexenepropionates 2 with (R)-phenylglycinol, the
      stereoselective hydrogenation of the resulting unsaturated tricyclic lactams, and
      the stereoselective reductive cleavage of the oxazolidine ring.

PMID- 19118478
TI  - Revision of purity criteria for tested compounds.

PMID- 19118481
TI  - Photodissociation dynamics of nitromethane at 226 and 271 nm at both nanosecond
      and femtosecond time scales.
AB  - Photodissociation of nitromethane has been investigated for decades both
      theoretically and experimentally; however, as a whole picture, the dissociation
      dynamics for nitromethane are still not clear, although many different mechanisms
      have been proposed. To make a complete interpretation of these different
      mechanisms, photolysis of nitromethane at 226 and 271 nm under both collisional
      and collisionless conditions is investigated at nanosecond and femtosecond time
      scales. These two laser wavelengths correspond to the pi* <-- pi and pi* <-- n
      excitations of nitromethane, respectively. In nanosecond 226 nm (pi* <-- pi)
      photolysis experiments, CH(3) and NO radicals are observed as major products
      employing resonance enhanced multiphoton ionization techniques and time-of-flight
      mass spectrometry. Additionally, OH and CH(3)O radicals are weakly observed as
      dissociation products employing laser induced fluorescence spectroscopy; the
      CH(3)O product is only observed under collisional conditions. In femtosecond 226
      nm experiments, CH(3), NO(2), and NO products are observed. These results confirm
      that rupture of C-N bond should be the main primary process for the photolysis of
      nitromethane after the pi* <-- pi excitation at 226 nm, and the NO(2) molecule
      should be the precursor of the observed NO product. Formation of the CH(3)O
      radical after the recombination of CH(3) and NO(2) species under collisional
      conditions rules out a nitro-nitrite isomerization mechanism for the generation
      of CH(3)O and NO from pi pi* CH(3)NO(2). The OH radical formation for pi pi*
      CH(3)NO(2) should be a minor dissociation channel because of the weak OH signal
      in both nanosecond and femtosecond (nonobservable) experiments. Single color
      femtosecond pump-probe experiments at 226 nm are also employed to monitor the
      dynamics of the dissociation of nitromethane after the pi* <-- pi excitation.
      Because of the ultrafast dynamics of product formation at 226 nm, the pump-probe
      transients for the three dissociation products are measured as an autocorrelation
      of the laser pulse, indicating the dissociation of nitromethane in the pi pi*
      excited state is faster than the laser pulse duration (180 fs). In nanosecond 271
      nm (pi* <-- n) photolysis experiments, pump-probe experiments are performed to
      detect potential dissociation products, such as CH(3), NO(2), CH(3)O, and OH;
      however, none of them is observed. In femtosecond 271 nm laser experiments, the
      nitromethane parent ion is observed with major intensity, together with CH(3),
      NO(2), and NO fragment ions with only minor intensities. Pump-probe transients
      for both nitromethane parent and fragment ions at 271 nm excitation and 406.5 nm
      ionization display a fast exponential decay with a constant time of 36 fs, which
      we suggest to be the lifetime of the excited n pi* state of nitromethane.
      Combined with the 271 nm nanosecond pump-probe experiments, in which none of the
      CH(3), NO(2), CH(3)O, or OH fragment is observed, we suggest that all the
      fragment ions generated in 271 nm femtosecond laser experiments are derived from
      the parent ion, and dissociation of nitromethane from the n pi* excited
      electronic state does not occur in a supersonic molecular beam under
      collisionless conditions.

PMID- 19118482
TI  - Primary atmospheric oxidation mechanism for toluene.
AB  - The products of the primary OH-initiated oxidation of toluene were investigated
      using the turbulent flow chemical ionization mass spectrometry technique at
      temperatures ranging from 228 to 298 K. A major dienedial-producing pathway was
      detected for the first time for toluene oxidation, and glyoxal and methylglyoxal
      were found to be minor primary oxidation products. The results suggest that
      secondary oxidation processes involving dienedial and epoxide primary products
      are likely responsible for previous observations of glyoxal and methylglyoxal
      products from toluene oxidation. Because the dienedial-producing pathway is a
      null cycle for tropospheric ozone production and glyoxal and methylglyoxal are
      important secondary organic aerosol precursors, these new findings have important
      implications for the modeling of toluene oxidation in the atmosphere.

PMID- 19118483
TI  - Products and kinetics of the liquid-phase reaction of glyoxal catalyzed by
      ammonium ions (NH4(+)).
AB  - Glyoxal, a common atmospheric gas, has been reported to be depleted in some
      regions of the atmosphere. The corresponding sink could be accounted for by
      reactions in or at the surface of atmospheric particles, but these reactions were
      not identified. Recently, we showed that inorganic ammonium ions, NH(4)(+), are
      efficient catalysts for reactions of carbonyl compounds, including glyoxal, in
      the liquid phase. To determine whether ammonium-catalyzed reactions can
      contribute to depletion of glyoxal in the atmosphere, the reactivity of this
      compound in aqueous solutions containing ammonium salts (ammonium sulfate,
      chloride, fluoride, and phosphate) at 298 K has been studied. The products
      identified by LC-HRMS and UV absorption revealed a mechanism involving two
      distinct pathways: a Bronsted acid pathway and an iminium pathway. The kinetics
      of the iminium pathway was studied by monitoring formation of a specific product.
      This pathway was second order in glyoxal in most of the solutions studied and
      should therefore be second order in most ammonium-containing aerosols in the
      atmosphere. The corresponding rate constant, k(II) (M(-1) s(-1)), increased
      strongly with ammonium ion activity, a(NH(4)(+)), and pH: k(II) (M(-1) s(-1)) =
      (2 +/- 1) x 10(-10) exp((1.5 +/- 0.8)aNH(4)(+)) exp((2.5 +/- 0.2)pH). This
      iminium pathway is a lower limit for the ammonium-catalyzed consumption of
      glyoxal, but the contribution of the acid pathway is expected to be small in
      tropospheric aerosols. With these results the reactive uptake of glyoxal on
      ammonium-containing aerosols was estimated and shown to be a possible explanation
      for depletion of this compound in Mexico City.

PMID- 19118484
TI  - Modulation of tris(o-phenylenedioxy)cyclotrisphosphazene (TPP) properties for
      zeolite use: effect of pi-conjugation length and CH/N heterosubstitution.
AB  - Highly accurate quantum chemical calculations were used in a comparative study of
      the pi-conjugation length and CH/N heterosubstitution effects on the structure
      and a number of properties of tris(o-phenylenedioxy)cyclotrisphosphazene (TPP)
      derivatives to identify the role of each of them in the modulation of the
      host...guest complex stability and available space for the adsorbate within TPP
      like organic zeolite (OZ). From the BH&HLYP/6-31G(d,p) structures it was found
      that extending the side fragment with a phenyl ring and substituting CH/N
      preserve the "paddle wheel" molecular shape, a key factor in the tunnel formation
      on which the organic zeolite use of TPP is based on. Compared to the
      unsubstituted molecules, the side fragment is shortened for CH/N
      heterosubstitution, which may decrease the diameter of the tunnel. In addition,
      through accurate ionization potential (IP) calculations (at the HF/6-311+G(d)
      level) the electron-donor (E-D) capacity was found to be more significantly
      enhanced by a lateral than a linear extension with phenyl ring, while it
      decreased upon CH/N heterosubstitution, which can affect the stability of some
      related host...guest complexes in the same order. Finally, as recently reported
      for TPP, the current results based on PBE0/6-31G(d,p) show that upon release of
      an electron the structural stability may not be altered by a CH/N mono- or
      disubstitution. From these features it was concluded that if the crystal
      requirement can be attained clathrates of good tolerance toward guest molecules
      in a wide range of Lewis acidity with variable E-D strength and available space
      for adsorbates may be reasonably awaited by exploiting these two approaches.

PMID- 19118486
TI  - Li-ion diffusion in the equilibrium nanomorphology of spinel Li(4+x)Ti(5)O(12).
AB  - Li(4)Ti(5)O(12) spinel as Li-ion electrode material combines good capacity,
      excellent cycleability with a high rate capability. Although the potential of
      about 1.56 V vs Li is relatively high, these features make it the anode of choice
      for state of the art high power Li-ion batteries. Although the flat voltage
      profile reflects a two-phase reaction during lithiation, the small change in
      lattice parameters upon lithiation ("zero-strain" property) leads to a solid
      solution in equilibrium, as recently demonstrated with diffraction. In this
      study, the morphology and Li-ion mobility is studied by NMR spectroscopy leading
      to a more detailed picture, showing that the solid solution in Li(4+x)Ti(5)O(12)
      spinel should actually be described as domains with sizes less than 9 nm having
      either tetrahedral (8a) Li occupation or octahedral (16c) Li occupation. The
      abundant domain boundaries and the associated disorder appear to be responsible
      for the facile diffusion through the lattice, and hence these nm-sized domains
      are most likely the origin of the relative high rate capability of this material
      as electrode for Li-ion batteries. The small domain size, smaller than typical
      Debye lengths, makes that the material electrochemically behaves as a solid
      solution. As such, the results give insight in the fundamental properties of the
      "zero-strain" Li(4)Ti(5)O(12) spinel material explaining the favorable Li-ion
      battery electrode properties on an atomic level.

PMID- 19118487
TI  - Titratable amino acid solvation in lipid membranes as a function of protonation
      state.
AB  - Knowledge about the insertion and stabilization of membrane proteins is a key
      step toward understanding their function and enabling membrane protein design.
      Transmembrane helices are normally quite hydrophobic so as to efficiently insert
      into membranes, but there are many exceptions with polar or titratable residues.
      An obvious example is the S4 helices of voltage-gated ion channels with up to 4
      arginines, leading to vivid discussion about whether such helices can insert
      spontaneously, and if so, what their conformation, protonation state, and cost of
      insertion really are. To address this question, we have determined geometric and
      energetic solvation properties for different protonation states of the
      titrateable amino acids, including hydration, side chain orientation, free energy
      profiles, and effects on the membrane thickness. As expected, charged states are
      significantly more expensive to insert (8-16 kcal/mol) than neutral variants (1-3
      kcal/mol). Although both sets of values exhibit quite high relative correlation
      with experimental in vivo hydrophobicity scales, the magnitudes of the in vivo
      hydrophobicity scales are much lower and strikingly appears as a compressed
      version of the calculated values. This agrees well with computational studies on
      longer lipids but results in an obvious paradox: the differences between in vivo
      insertion and simulations cannot be explained by methodological differences in
      force fields, possible limited hydrophobic thickness of the endoplasmic reticulum
      (ER) membrane, or parameters; even anionic lipid head groups (PG) only have
      limited effect on charged side chains, and virtually none for hydrophobic ones.
      This leads us to propose a model for in vivo insertion that could reconcile these
      differences and explain the correlation: if there are considerable hydrophobic
      barriers inside the translocon, the experimental reference state for the
      solvation free energy when comparing insertion/translocation in vivo would be
      quite close to the bilayer environment rather than water.

PMID- 19118488
TI  - Utilizing the charge field effect on amide (15)N chemical shifts for protein
      structure validation.
AB  - Of all the nuclei in proteins, the nuclear magnetic resonance (NMR) chemical
      shifts of nitrogen are the theoretically least well understood. In this study,
      quantum chemical methods are used in combination with polarizable-continuum
      models in order to show that consideration of the effective electric field,
      including charge screening due to solvation, improves considerably the
      consistencies of statistical relationships between experimental and computed
      amide (15)N shifts between various sets of charged and uncharged oligopeptides
      and small organic molecules. A single conversion scheme between shielding
      parameters from first principles using density functional theory (DFT) and
      experimental shifts is derived that holds for all classes of compounds examined
      here. This relationship is then used to test the accuracy of such (15)N chemical
      shift predictions in the cyclic decapeptide antibiotic gramicidin S (GS). GS has
      previously been studied in great detail, both by NMR and X-ray crystallography.
      It adopts a well-defined backbone conformation, and hence, only a few discrete
      side chain conformational states need to be considered. Moreover, a charge-relay
      effect of the two cationic ornithine side chains to the protein backbone has been
      described earlier by NMR spectroscopy. Here, DFT-derived backbone amide nitrogen
      chemical shifts were calculated for multiple conformations of GS. Overall, the
      structural dynamics of GS is revisited in view of chemical shift behavior along
      with energetic considerations. Together, the study demonstrates proof of concept
      that (15)N chemical shift information is particularly useful in the analysis and
      validation of protein conformational states in a charged environment.

PMID- 19118489
TI  - A novel one-step synthesis of imidazo[5,1-a]isoquinolines via a tandem Pd
      catalyzed alkylation-direct arylation sequence.
AB  - A palladium-catalyzed/norbornene-mediated one-step synthesis of highly
      functionalized imidazoles via a sequential alkyl-aryl and aryl-heteroaryl bond
      formation is devised. This method provides an efficient route to a wide variety
      of substituted imidazo[5,1-a]isoquinolines from readily accessible N-bromoalkyl
      imidazoles and aryl iodides.

PMID- 19118490
TI  - End-organ dysfunction and cardiovascular outcomes: the role of the
      microcirculation.
AB  - Risk factors for cardiovascular disease mediate their effects by altering the
      structure and function of wall and endothelial components of arterial blood
      vessels. A pathological change in the microcirculation plays a pivotal role in
      promoting end-organ dysfunction that not only predisposes to further organ
      damage, but also increases the risk for future macrovascular events. The
      microcirculation is recognized as the site where the earliest manifestations of
      cardiovascular disease, especially inflammatory responses, occur that may play a
      pivotal role in driving the atherosclerotic process in conduit vessels.
      Furthermore, the vast surface area of the endothelium compared with conduit
      vessels means that the vascular effects of endothelial dysfunction or activation
      will be most apparent in this section of the vasculature. Current techniques
      providing indices of vascular health focus on large arteries without providing
      insight into the structure and function of small vessels. Techniques capable of
      detecting microvascular damage and monitoring the response to therapeutic
      interventions, especially in vulnerable target organs of interest, may improve
      risk stratification and represent a valuable surrogate for future cardiovascular
      outcome.

PMID- 19118491
TI  - FoxO proteins: cunning concepts and considerations for the cardiovascular system.
AB  - Dysfunction in the cardiovascular system can lead to the progression of a number
      of disease entities that can involve cancer, diabetes, cardiac ischaemia,
      neurodegeneration and immune system dysfunction. In order for new therapeutic
      avenues to overcome some of the limitations of present clinical treatments for
      these disorders, future investigations must focus upon novel cellular processes
      that control cellular development, proliferation, metabolism and inflammation. In
      this respect, members of the mammalian forkhead transcription factors of the O
      class (FoxOs) have increasingly become recognized as important and exciting
      targets for disorders of the cardiovascular system. In the present review, we
      describe the role of these transcription factors in the cardiovascular system
      during processes that involve angiogenesis, cardiovascular development,
      hypertension, cellular metabolism, oxidative stress, stem cell proliferation,
      immune system regulation and cancer. Current knowledge of FoxO protein function
      combined with future studies should continue to lay the foundation for the
      successful translation of these transcription factors into novel and robust
      clinical therapies.

PMID- 19118494
TI  - A model to prioritize access to elective surgery on the basis of clinical urgency
      and waiting time.
AB  - BACKGROUND: Prioritization of waiting lists for elective surgery represents a
      major issue in public systems in view of the fact that patients often suffer from
      consequences of long waiting times. In addition, administrative and standardized
      data on waiting lists are generally lacking in Italy, where no detailed national
      reports are available. This is true although since 2002 the National Government
      has defined implicit Urgency-Related Groups (URGs) associated with Maximum Time
      Before Treatment (MTBT), similar to the Australian classification. The aim of
      this paper is to propose a model to manage waiting lists and prioritize
      admissions to elective surgery. METHODS: In 2001, the Italian Ministry of Health
      funded the Surgical Waiting List Info System (SWALIS) project, with the aim of
      experimenting solutions for managing elective surgery waiting lists. The project
      was split into two phases. In the first project phase, ten surgical units in the
      largest hospital of the Liguria Region were involved in the design of a pre
      admission process model. The model was embedded in a Web based software, adopting
      Italian URGs with minor modifications. The SWALIS pre-admission process was based
      on the following steps: 1) urgency assessment into URGs; 2) correspondent
      assignment of a pre-set MTBT; 3) real time prioritization of every referral on
      the list, according to urgency and waiting time. In the second project phase a
      prospective descriptive study was performed, when a single general surgery unit
      was selected as the deployment and test bed, managing all registrations from
      March 2004 to March 2007 (1809 ordinary and 597 day cases). From August 2005,
      once the SWALIS model had been modified, waiting lists were monitored and
      analyzed, measuring the impact of the model by a set of performance indexes
      (average waiting time, length of the waiting list) and Appropriate Performance
      Index (API). RESULTS: The SWALIS pre-admission model was used for all
      registrations in the test period, fully covering the case mix of the patients
      referred to surgery. The software produced real time data and advanced
      parameters, providing patients and users useful tools to manage waiting lists and
      to schedule hospital admissions with ease and efficiency. The model protected
      patients from horizontal and vertical inequities, while positive changes in API
      were observed in the latest period, meaning that more patients were treated
      within their MTBT. CONCLUSION: The SWALIS model achieves the purpose of providing
      useful data to monitor waiting lists appropriately. It allows homogeneous and
      standardized prioritization, enhancing transparency, efficiency and equity. Due
      to its applicability, it might represent a pragmatic approach towards surgical
      waiting lists, useful in both clinical practice and strategic resource
      management.

PMID- 19118492
TI  - PPARgamma and its ligands: therapeutic implications in cardiovascular disease.
AB  - The relevance of PPARgamma (peroxisome-proliferator-activated receptor gamma) as
      an important therapeutic target for the treatment of diabetes arises from its
      hypoglycaemic effects in diabetic patients and also from the critical role in the
      regulation of cardiovascular functions. From a clinical perspective, differences
      between current FDA (Food and Drug Administration)-approved PPARgamma drugs have
      been observed in terms of atherosclerosis and cardiac and stroke events. The
      adverse effects of PPARgamma-specific treatments that hamper their cardiovascular
      protective roles, affirm the strong need to evaluate the efficacy of the current
      drugs. Therefore active research is directed towards high-throughput screening
      and pharmacological testing of a plethora of newly identified natural or
      synthetic compounds. In the present review we describe the rationale behind drug
      design strategies targeting PPARgamma, based on current knowledge regarding the
      effects of such drugs in experimental animal models, as well as in clinical
      practice. Regarding endogenous PPARgamma ligands, several fatty acid derivatives
      bind PPARgamma with different affinities, although the physiological relevance of
      these interactions is not always evident. Recently, NO-derived unsaturated fatty
      acids were found to be potent agonists of PPARs, with preferential affinity for
      PPARgamma, compared with oxidized fatty acid derivatives. Nitroalkenes exert
      important bioactivities of relevance for the cardiovascular system including anti
      inflammatory and antiplatelet actions, and are important mediators of vascular
      tone. A new generation of insulin sensitizers with PPARgamma function for the
      treatment of diabetes may serve to limit patients from the increased
      cardiovascular burden of this disease.

PMID- 19118493
TI  - Role of TNF-alpha in vascular dysfunction.
AB  - Healthy vascular function is primarily regulated by several factors including
      EDRF (endothelium-dependent relaxing factor), EDCF (endothelium-dependent
      contracting factor) and EDHF (endothelium-dependent hyperpolarizing factor).
      Vascular dysfunction or injury induced by aging, smoking, inflammation, trauma,
      hyperlipidaemia and hyperglycaemia are among a myriad of risk factors that may
      contribute to the pathogenesis of many cardiovascular diseases, such as
      hypertension, diabetes and atherosclerosis. However, the exact mechanisms
      underlying the impaired vascular activity remain unresolved and there is no
      current scientific consensus. Accumulating evidence suggests that the
      inflammatory cytokine TNF (tumour necrosis factor)-alpha plays a pivotal role in
      the disruption of macrovascular and microvascular circulation both in vivo and in
      vitro. AGEs (advanced glycation end-products)/RAGE (receptor for AGEs), LOX-1
      [lectin-like oxidized low-density lipoprotein receptor-1) and NF-kappaB (nuclear
      factor kappaB) signalling play key roles in TNF-alpha expression through an
      increase in circulating and/or local vascular TNF-alpha production. The increase
      in TNF-alpha expression induces the production of ROS (reactive oxygen species),
      resulting in endothelial dysfunction in many pathophysiological conditions. Lipid
      metabolism, dietary supplements and physical activity affect TNF-alpha
      expression. The interaction between TNF-alpha and stem cells is also important in
      terms of vascular repair or regeneration. Careful scrutiny of these factors may
      help elucidate the mechanisms that induce vascular dysfunction. The focus of the
      present review is to summarize recent evidence showing the role of TNF-alpha in
      vascular dysfunction in cardiovascular disease. We believe these findings may
      prompt new directions for targeting inflammation in future therapies.

PMID- 19118497
TI  - Peters plus syndrome and absence of kidney: a case report.
AB  - A case of bilateral Peters anomaly with missing kidney on left was examined. The
      case of missing kidney in Peters anomaly has not been reported in literature to
      our knowledge, making this case a unique one.

PMID- 19118496
TI  - Regularized gene selection in cancer microarray meta-analysis.
AB  - BACKGROUND: In cancer studies, it is common that multiple microarray experiments
      are conducted to measure the same clinical outcome and expressions of the same
      set of genes. An important goal of such experiments is to identify a subset of
      genes that can potentially serve as predictive markers for cancer development and
      progression. Analyses of individual experiments may lead to unreliable gene
      selection results because of the small sample sizes. Meta analysis can be used to
      pool multiple experiments, increase statistical power, and achieve more reliable
      gene selection. The meta analysis of cancer microarray data is challenging
      because of the high dimensionality of gene expressions and the differences in
      experimental settings amongst different experiments. RESULTS: We propose a Meta
      Threshold Gradient Descent Regularization (MTGDR) approach for gene selection in
      the meta analysis of cancer microarray data. The MTGDR has many advantages over
      existing approaches. It allows different experiments to have different
      experimental settings. It can account for the joint effects of multiple genes on
      cancer, and it can select the same set of cancer-associated genes across multiple
      experiments. Simulation studies and analyses of multiple pancreatic and liver
      cancer experiments demonstrate the superior performance of the MTGDR. CONCLUSION:
      The MTGDR provides an effective way of analyzing multiple cancer microarray
      studies and selecting reliable cancer-associated genes.

PMID- 19118495
TI  - Modeling ERBB receptor-regulated G1/S transition to find novel targets for de
      novo trastuzumab resistance.
AB  - BACKGROUND: In breast cancer, overexpression of the transmembrane tyrosine kinase
      ERBB2 is an adverse prognostic marker, and occurs in almost 30% of the patients.
      For therapeutic intervention, ERBB2 is targeted by monoclonal antibody
      trastuzumab in adjuvant settings; however, de novo resistance to this antibody is
      still a serious issue, requiring the identification of additional targets to
      overcome resistance. In this study, we have combined computational simulations,
      experimental testing of simulation results, and finally reverse engineering of a
      protein interaction network to define potential therapeutic strategies for de
      novo trastuzumab resistant breast cancer. RESULTS: First, we employed Boolean
      logic to model regulatory interactions and simulated single and multiple protein
      loss-of-functions. Then, our simulation results were tested experimentally by
      producing single and double knockdowns of the network components and measuring
      their effects on G1/S transition during cell cycle progression. Combinatorial
      targeting of ERBB2 and EGFR did not affect the response to trastuzumab in de novo
      resistant cells, which might be due to decoupling of receptor activation and cell
      cycle progression. Furthermore, examination of c-MYC in resistant as well as in
      sensitive cell lines, using a specific chemical inhibitor of c-MYC (alone or in
      combination with trastuzumab), demonstrated that both trastuzumab sensitive and
      resistant cells responded to c-MYC perturbation. CONCLUSION: In this study, we
      connected ERBB signaling with G1/S transition of the cell cycle via two major
      cell signaling pathways and two key transcription factors, to model an
      interaction network that allows for the identification of novel targets in the
      treatment of trastuzumab resistant breast cancer. Applying this new strategy, we
      found that, in contrast to trastuzumab sensitive breast cancer cells,
      combinatorial targeting of ERBB receptors or of key signaling intermediates does
      not have potential for treatment of de novo trastuzumab resistant cells. Instead,
      c-MYC was identified as a novel potential target protein in breast cancer cells.

PMID- 19118498
TI  - Bone mass in schizophrenia and normal populations across different decades of
      life.
AB  - BACKGROUND: Chronic schizophrenic patients have been reported as having higher
      osteoporosis prevalence. Survey the bone mass among schizophrenic patients and
      compare with that of the local community population and reported data of the same
      country to figure out the distribution of bone mass among schizophrenic patients.
      METHODS: 965 schizophrenic patients aged 20 years and over in Yuli Veterans
      Hospital and 405 members aged 20 and over of the community living in the same
      town as the institute received bone mass examination by a heel qualitative
      ultrasound (QUS) device. Bone mass distribution was stratified to analyzed and
      compared with community population. RESULTS: Schizophrenic patients have lower
      bone mass while they are young. But aging effect on bone mass cannot be seen.
      Accelerated bone mass loss during menopausal transition was not observed in the
      female schizophrenic patients as in the subjects of the community female
      population. CONCLUSION: Schizophrenic patients have lower bone mass than
      community population since they are young. Further study to investigate the
      pathophysiological process is necessary to delay or avoid the lower bone mass in
      schizophrenia patients.

PMID- 19118499
TI  - Is overexpression of HER-2 a predictor of prognosis in colorectal cancer?
AB  - BACKGROUND: The development of novel chemotherapeutic agents in colorectal cancer
      has improved survival. Following initial response to chemotherapeutic strategies
      many patients develop refractory disease. This poses a significant challenge
      common to many cancer subtypes. Newer agents such as Bevacizumab have
      successfully targeted the tyrosine kinase receptor epidermal growth factor
      receptor in metastatic colorectal cancer. Human epidermal growth factor receptor
      2 is another member of the tyrosine kinase receptor family which has been
      successfully targeted in breast cancer. This may play a role in colorectal
      cancer. We conducted a clinicopathological study to determine if overexpression
      of human epidermal growth factor receptor-2 is a predictor of outcome in a cohort
      of patients with colorectal cancer. METHODS: Clinicopathological data and
      paraffin-embedded specimens were collected on 132 consecutive patients who
      underwent colorectal resections over a 24-month period at Mayo General Hospital.
      Twenty-six contained non-malignant disease. Her-2/neu protein overexpression was
      detected using immunohistochemistry (IHC). The HER-2 4B5 Ventana monoclonal
      antibody was used. Fluorescent insitu hybridisation (FISH) was performed using
      INFORM HER-2/Neu Plus. Results were correlated with established clinical and
      pathological predictors of outcome including TNM stage. Statistical analysis was
      performed using SPSS version 11.5. RESULTS: 114 were HER-2/Neu negative using
      IHC, 7 showed barely perceptible positivity (1+), 9 showed moderate staining (2+)
      and 2 were strongly positive (3+). There was no correlation with gender, age,
      grade, Dukes' stage, TNM stage, time to recurrence and 5-year survival (p >
      0.05). FISH was applied to all 2+ and 3+ cases as well as some negative cases
      selected at random. Three were amplified (2 were 3+ and 1 was 2+). Similarly, HER
      2 gene overexpression did not correlate with established prognostic indicators.
      CONCLUSION: HER-2 protein is over expressed in 11% of colorectal cancer patients.
      The gene encoding HER-2 is amplified in 3% of cases. Overexpression of HER-2 is
      not a predictor of outcome. However, patients who over express HER-2 may respond
      to Herceptin therapy.

PMID- 19118500
TI  - Synthetic control of a fitness tradeoff in yeast nitrogen metabolism.
AB  - BACKGROUND: Microbial communities are involved in many processes relevant to
      industrial and medical biotechnology, such as the formation of biofilms,
      lignocellulosic degradation, and hydrogen production. The manipulation of
      synthetic and natural microbial communities and their underlying ecological
      parameters, such as fitness, evolvability, and variation, is an increasingly
      important area of research for synthetic biology. RESULTS: Here, we explored how
      synthetic control of an endogenous circuit can be used to regulate a tradeoff
      between fitness in resource abundant and resource limited environments in a
      population of Saccharomyces cerevisiae. We found that noise in the expression of
      a key enzyme in ammonia assimilation, Gdh1p, mediated a tradeoff between growth
      in low nitrogen environments and stress resistance in high ammonia environments.
      We implemented synthetic control of an endogenous Gdh1p regulatory network to
      construct an engineered strain in which the fitness of the population was tunable
      in response to an exogenously-added small molecule across a range of ammonia
      environments. CONCLUSION: The ability to tune fitness and biological tradeoffs
      will be important components of future efforts to engineer microbial communities.

PMID- 19118501
TI  - Combined xanthorrhizol-curcumin exhibits synergistic growth inhibitory activity
      via apoptosis induction in human breast cancer cells MDA-MB-231.
AB  - BACKGROUND: It has been suggested that combined effect of natural products may
      improve the treatment effectiveness in combating proliferation of cancer cells.
      The present study was undertaken to evaluate the possibility that the combination
      of xanthorrhizol and curcumin might show synergistic growth inhibitory effect
      towards MDA-MB-231 human breast cancer cells via apoptosis induction. The
      effective dose that produced 50% growth inhibition (GI50) was calculated from the
      log dose-response curve of fixed-combinations of xanthorrhizol and curcumin
      generated from the sulforhodamine B (SRB) assay. The experimental GI50 value was
      used to determine the synergistic activity of the combination treatment by
      isobolographic analysis and combination-index method. Further investigation of
      mode of cell death induced by the combination treatment was conducted in the
      present study. RESULTS: Isobole analysis revealed that substances interaction was
      synergistic when xanthorrhizol and curcumin were added concurrently to the
      cultures but merely additive when they were added sequentially. The synergistic
      combination treatment was then applied to the cultures to investigate the mode of
      cell death induced by the treatment. Immunofluorescence staining using antibody
      MitoCapturetrade mark revealed the possibility of altered mitochondrial
      transmembrane potential, which is one of the hallmark of apoptosis. Hoechst 33258
      nuclear staining assay showed the rate of apoptosis of MDA-MB-231 cells to
      increase in response to the treatment. Apoptotic cell death was further confirmed
      by DNA fragmentation assay, where internucleosomal excision of DNA was induced
      upon treatment with xanthorrhizol-curcumin. CONCLUSION: This is the first time
      the combined cytotoxic effect of xanthorrhizol and curcumin on MDA-MB-231 cells
      has been documented and our findings provide experimental support to the
      hypothesis that combined xanthorrhizol-curcumin showed synergistic growth
      inhibitory activity on MDA-MB-231 cells via apoptosis induction.

PMID- 19118503
TI  - Effects of Ginkgo biloba on airway histology in a mouse model of chronic asthma.
AB  - Platelet-activating factor (PAF) is an inflammatory mediator involved in the
      pathophysiology of asthma, suggesting a therapy antagonizing its effects may play
      a role in the disease treatment. The aim of the study was to determine the
      effects of Ginkgo biloba, a PAF antagonist, on lung histology. Thirty-five BALB/c
      mice were divided into five groups; A, B, C, D, and the control. All mice except
      controls were sensitized and challenged with ovalbumin. Mice in group A (placebo)
      received saline; group B received G. biloba, 100 mg/kg; group C received G.
      biloba, 150 mg/kg; and group D received dexamethasone, 1 mg/kg via orogastric
      gavage for 7 consecutive days. Chronic structural changes and airway remodeling
      were evaluated by using light and electron microscopy in all groups. Evaluation
      of lung histology indicated that the number of goblet cells, mast cells,
      thicknesses of epithelium, and basement membrane were significantly improved in
      groups B and C when compared with group A. There was no statistically significant
      difference in thicknesses of subepithelial smooth muscle between groups A, B, and
      C. When doses of G. biloba were compared with each other, only the number of
      goblet cells was significantly lower in group C than in group B. When G. biloba
      and dexamethasone groups were compared with each other, thicknesses of basement
      membrane and subepithelial smooth muscle were found to be lower in group D than
      in groups B and C. G. biloba alleviates all established chronic histological
      changes of lung except smooth muscle thickness in a mouse model of asthma.

PMID- 19118502
TI  - Identification and bioinformatic characterization of a multidrug resistance
      associated protein (ABCC) gene in Plasmodium berghei.
AB  - BACKGROUND: The ATP-binding cassette (ABC) superfamily is one of the largest
      evolutionarily conserved families of proteins. ABC proteins play key roles in
      cellular detoxification of endobiotics and xenobiotics. Overexpression of certain
      ABC proteins, among them the multidrug resistance associated protein (MRP),
      contributes to drug resistance in organisms ranging from human neoplastic cells
      to parasitic protozoa. In the present study, the Plasmodium berghei mrp gene
      (pbmrp) was partially characterized and the predicted protein was classified
      using bioinformatics in order to explore its putative involvement in drug
      resistance. METHODS: The pbmrp gene from the P. berghei drug sensitive, N clone,
      was sequenced using a PCR strategy. Classification and domain organization of
      pbMRP were determined with bioinformatics. The Plasmodium spp. MRPs were aligned
      and analysed to study their conserved motifs and organization. Gene copy number
      and organization were determined via Southern blot analysis in both N clone and
      the chloroquine selected line, RC. Chromosomal Southern blots and RNase
      protection assays were employed to determine the chromosomal location and
      expression levels of pbmrp in blood stages. RESULTS: The pbmrp gene is a single
      copy, intronless gene with a predicted open reading frame spanning 5820
      nucleotides. Bioinformatic analyses show that this protein has distinctive
      features characteristic of the ABCC sub-family. Multiple sequence alignments
      reveal a high degree of conservation in the nucleotide binding and transmembrane
      domains within the MRPs from the Plasmodium spp. analysed. Expression of pbmrp
      was detected in asexual blood stages. Gene organization, copy number and mRNA
      expression was similar in both lines studied. A chromosomal translocation was
      observed in the chloroquine selected RC line, from chromosome 13/14 to chromosome
      8, when compared to the drug sensitive N clone. CONCLUSION: In this study, the
      pbmrp gene was sequenced and classified as a member of the ABCC sub-family.
      Multiple sequence alignments reveal that this gene is homologous to the
      Plasmodium y. yoelii and Plasmodium knowlesi mrp, and the Plasmodium vivax and
      Plasmodium falciparum mrp2 genes. There were no differences in gene organization,
      copy number, or mRNA expression between N clone and the RC line, but a
      chromosomal translocation of pbmrp from chromosome 13/14 to chromosome 8 was
      detected in RC.

PMID- 19118505
TI  - Generation and regulation of CD8(+) regulatory T cells.
AB  - Research into the suppressive activity of CD4(+)FoxP3(+) T regulatory cells
      (Treg) has defined a sublineage of CD4(+) cells that contribute to self-tolerance
      and resistance to autoimmune disease. Much less attention has been given to the
      potential contribution of regulatory sublineages of CD8(+) cells. Analysis of a
      small fraction of CD8(+) cells that target autoreactive CD4(+) cells through
      recognition of the MHC class Ib molecule Qa-1 in mouse and HLA-E in human has
      revitalized interest in CD8(+) Treg. Here we summarize recent progress and future
      directions of research into the role of this CD8(+) sublineage in resistance to
      autoimmune disease.

PMID- 19118506
TI  - Acquired pMHC I complexes greatly enhance CD4(+) Th cell's stimulatory effect on
      CD8(+) T cell-mediated diabetes in transgenic RIP-mOVA mice.
AB  - CD4(+) helper T (Th) cells play pivotal roles in induction of CD8(+) CTL
      immunity. However, the mechanism of CD4(+) T cell help delivery to CD8(+) T cells
      in vivo is still elusive. In this study, we used ovalbumin (OVA)-pulsed dendritic
      cells (DC(OVA)) to activate OT-II mouse CD4(+) T cells, and then studied the help
      effect of these CD4(+) T cells on CD8(+) cytotoxic T lymphocyte (CTL) responses.
      We also examined CTL mediated islet beta cell destruction which led to diabetes
      in wild-type C57BL/6 mice and transgenic rat insulin promoter (RIP)-mOVA mice
      expressing beta cell antigen OVA with self OVA-specific tolerance, respectively.
      In adoptive transfer experiments, we demonstrated that help, in the form of
      peptide/major histocompatibility complex (pMHC) I acquired from DC(OVA) by
      DC(OVA) activation, was required for induction of OVA-specific CTL responses in
      C57BL/6 mice. However, in combination with TCR transgenic OT-I mouse CD8(+) T
      cells, the tolerogenic dosage of CD4(+) Th cells with acquired pMHC I, but not
      CD4(+) K(b-/-) Th cells without acquired pMHC I were able to cause diabetes in
      8/10 (80%) RIP-mOVA mice. This study thus expands the current knowledge in T cell
      mediated autoimmunity and provides insight into the nature of CD4(+) T cell
      mediated help in CD8(+) CTL induction.

PMID- 19118507
TI  - Transplantation of human bone marrow mesenchymal stem cell ameliorates the
      autoimmune pathogenesis in MRL/lpr mice.
AB  - Recent evidence indicates that mesenchymal stem cells (MSC) possess
      immunosuppressive properties both in vitro and in vivo. We previously
      demonstrated the functional abnormality of bone marrow derived MSC in patients
      with systemic lupus erythematosus (SLE). In this study, we aimed to investigate
      whether transplantation of human bone marrow derived MSC affects the autoimmune
      pathogenesis in MRL/lpr mice. We found that human MSC from healthy donors reduced
      the proliferation of T lymphocytes from MRL/lpr mice in a dose-dependent fashion.
      Two weeks after in vivo transfer of MSC, we detected significantly reduced serum
      levels of anti ds-DNA antibodies and 24 hour proteinuria in MRL/lpr mice as
      compared with control groups without MSC transplantation. Moreover, flow
      cytometric analysis revealed markedly reduced number of CD4(+) T cells while
      increased Th1 subpopulation in MSC group and MSC + CTX group when compared with
      controls. Histopathological examination showed significantly reduced renal
      pathology in MSC-treated mice. Immunohistochemical studies further revealed
      reduced expression of TGF-beta, FN, VEGF and the deposition of complement C3 in
      renal tissue after MSC and MSC + CTX treatment. Taken together, we have
      demonstrated that transplantation of human MSC can significantly inhibit the
      autoimmune progression in MRL/lpr mice.

PMID- 19118508
TI  - Inhibitory effect of recombinant IL-25 on the development of dextran sulfate
      sodium-induced experimental colitis in mice.
AB  - The role of interleukin 25 (IL-25) in a number of human diseases still has not
      been extensively studied, here we attempt to evaluate the role of recombinant IL
      25 (rIL-25) in the development of dextran sulfate sodium (DSS)-induced
      experimental colitis. Acute colitis was induced in female C57BL/6 mice by oral
      administration of 2.5% DSS in drinking water ad libitum. At the same time as the
      start of DSS exposure, mice were injected intraperitoneally with 0.4 microg of
      rIL-25 or PBS. Then disease activity index (DAI), histological changes and
      survival rate were observed. The levels of IL-17, IL-23, and TGF-beta1 in colon
      tissues were determined by ELISA, and the production of IL-17 by CD4(+)/CD8(+) T
      cells was detected by intracellular flow cytometry. In contrast to the DSS
      treated mice, DSS + rIL-25 treated mice displayed a lower DAI, limited
      histological changes and prolonged survival. The levels of IL-23 and TGF-beta1
      were significantly elevated in the DSS + rIL-25 treated mice compared to the DSS
      treated mice. There was no significant difference in the production of IL-17 in
      colon tissues and CD4(+)/CD8(+) T cells between the DSS + rIL-25 treated mice and
      DSS treated mice. Our findings suggest the role of IL-25 in inhibiting
      development and progression of acute colitis in DSS-induced mouse colitis model.

PMID- 19118509
TI  - Inhibition of the antigen-induced activation of RBL-2H3 cells by Gab2 siRNA.
AB  - Gab2 plays an important role in FcepsilonRI mediated signal events which lead to
      degranulation from mast cells. The present study was designed to investigate the
      effect of the synthetic Gab2 (scaffolding adapter Grb2-associated binder 2) siRNA
      on the antigen-induced activation of RBL-2H3 cells. A double stranded siRNA
      against Gab2-mRNA was synthesized and transfected into RBL-2H3 cells. After 6 h,
      cells were then sensitized with dinitrophenyl (DNP)-specific IgE overnight and
      challenged with dinitrophenyl-human serum albumin (DNP-HSA) to induce mast cell
      degranulation before supernatants were collected. Effects of Gab2 siRNA on
      antigen-induced release of beta-hexosaminidase and histamine, cytokine production
      and regulation of the proteins in the pathway were measured by enzymatic assay,
      EIA, ELISA and Western blotting. Treatment with Gab2 siRNA significantly
      decreased Gab2 expression, inhibited the FcepsilonRI-mediated mast cell release
      of beta-hexosaminidase and histamine, reduced the production of IL-4 and TNF
      alpha and inhibited the phosphorylation of Akt, PKCdelta and p38 mitogen
      activated protein kinase (MAPK). Data showed that Gab2 siRNA could suppress the
      antigen-induced activation of RBL-2H3 cells and suggested a possible mechanism
      through inhibition of signaling molecules downstream of Gab2 in the FcepsilonRI
      mediated Ca(2+)-independent pathway. Furthermore, potential usefulness of Gab2
      knock-down as a method for inhibition of mast cell-mediated allergic reactions
      was demonstrated.

PMID- 19118510
TI  - Protection of immuno-compromised mice from lethal infection of Klebsiella
      pneumonia by rAAV2-BPI23-Fcgamma1 gene transfer.
AB  - In previous research, chimerical BPI23-Fcgamma1 gene which consisted of human
      bactericidal/permeability increasing protein (BPI) gene of encoding the
      functional N terminus (amino acid residues 1 to 199) of human BPI and Fcgamma1
      gene of encoding the Fc segment of human immunoglobulin G1 was successfully
      reconstructed within a recombinant adeno-associated virus serotype 2 (rAAV2)
      vector as rAAV2-BPI23-Fcgamma1. Here, to evaluate the potentiality of applying
      gene therapy to gram negative bacterial (GNB) infection in high-risk patients, we
      investigated protection of immuno-compromised mice and immunocompetent mice from
      challenge with minimal lethal dose (MLD) Klebsiella pneumonia infection after
      rAAV2-BPI23-Fcgamma1 gene transferred. The results showed that the survival rate
      of rAAV2-BPI23-Fcgamma1 transferred immunocompetent mice as well as immuno
      compromised mice (40.0% and 44.4%, respectively) were significantly higher than
      that of corresponding control mice (6.7% and 4.4%, respectively); the bacteria
      counting, level of endotoxin and proinflammatory cytokines in the rAAV2-BPI23
      Fcgamma1 transferred immuno-compromised mice were markedly lower than that of
      rAAV2-EGFP and rAAV2-Null transferred immuno-compromised mice. Our data suggest
      that rAAV2-BPI23-Fcgamma1 gene transferring offered immuno-compromised mice with
      resistance against GNB infection, so it is quite potential in preventing GNB
      infection of clinical high-risk patients.

PMID- 19118511
TI  - The Leu477 and Leu613 of ORF2-encoded protein are critical in forming
      neutralization antigenic epitope of hepatitis E virus genotype 4.
AB  - Hepatitis E virus (HEV) genotype 4 was originally identified in China. Its
      neutralization antigenic epitopes have not been characterized. Recently, we
      identified a neutralizing monoclonal antibody (mAb) 1G10, which was generated
      following immunization of mice with p166Chn, a recombinant protein comprising 464
      629 amino acids (aa) of the HEV genotype 4 capsid protein. In this study, a panel
      of 22 N- and/or C-terminal truncated and 6 site-directed mutated p166Chn proteins
      were prepared. Only those N- or C-terminal truncated proteins containing the
      region 477-613 aa could react with the mAb 1G10, suggesting the neutralization
      epitope of HEV genotype 4 is located between aa477 and aa613. However, a both N-
      and C-terminal truncated protein, pN477-C613, neither reacted to 1G10 nor
      elicited neutralizing antibodies in mice, while another both terminal truncated
      protein, pN472-C617, did, suggesting the flanking regions of the pN477-C613 could
      help to stabilize and allow presentation of the neutralization epitope to the
      immune system. Substituting Leu477 and/or Leu613 with the polar, uncharged
      threonine (Thr) caused > or =50% reduction of the mutants' immunoreactivity to
      1G10, whereas replacement by hydrophobic phenylalanine (Phe) made little impact
      on the immunoreactivity, revealing functional associations between hydrophobicity
      of aa at positions 477 and 613 and the antigenicity of p166Chn. These data
      suggested Leu477 and Leu613 are critical in forming the neutralization epitope of
      HEV genotype 4.

PMID- 19118512
TI  - Association of KIR genotypes and haplotypes with susceptibility to chronic
      hepatitis B virus infection in Chinese Han population.
AB  - Killer immunoglobulin-like receptor (KIR) genes can regulate the activation of NK
      and T cells upon interaction with HLA class I molecules. Hepatitis B virus (HBV)
      infection has been regarded as a multi-factorial disorder disease. Previous
      studies revealed that KIRs were involved in HCV and HIV infection or clearance.
      The aim of this study was to explore the possibility of the inheritance of KIR
      genotypes and haplotypes as a candidate for susceptibility to persistent HBV
      infection or HBV clearance. The sequence specific primer polymerase chain
      reaction (SSP-PCR) was employed to identify the KIR genes and pseudogenes in 150
      chronic hepatitis B (CHB) patients, 251 spontaneously recovered (SR) controls,
      and 412 healthy controls. The frequencies of genotype G, M, FZ1 increased in CHB
      patients compared with healthy control subjects. The frequency of genotype AH was
      higher in SR controls than that in both CHB patients and healthy controls. The
      carriage frequencies of genotype G and AH were higher; while, the frequencies of
      AF and AJ were lower in SR controls than those in healthy control subjects. The
      frequency of A haplotype was lower, whereas, the frequency of B haplotype was
      higher in CHB patients and SR controls than those in healthy controls. In healthy
      controls, haplotype 4 was found lower compared with that in CHB patients and SR
      controls and the frequency of haplotype 5 was higher in SR controls than that in
      other two groups. Based on these findings, it seems that the genotypes M and FZ1
      are HBV susceptive genotypes; AH, on the other hand, may be protective genotypes
      that facilitate the clearance of HBV. It appears that the haplotype 4 is HBV
      susceptive haplotype, whereas, haplotype 5 may be the protective haplotype that
      facilitates the clearance of HBV.

PMID- 19118513
TI  - The abnormal high expression of B cell activating factor belonging to TNF
      superfamily (BAFF) and its potential role in kidney transplant recipients.
AB  - B cell activating factor belonging to TNF superfamily (BAFF) is a critical
      regulator of B cell maturation and survival. In this present study, the
      expression characteristic of BAFF in kidney transplantation recipients was
      investigated, its potential significance was analyzed and peripheral blood of
      follow-up kidney transplant recipients was studied. Flow cytometric assay results
      showed that, cell-surface BAFF was significantly highly expressed on peripheral
      CD3(+) T lymphocytes in > or = 5 yrs group of kidney transplant recipients,
      compared with other groups (p < 0.05). BAFF expression could be found on CD4(+) T
      cells and CD8(+) T cells. The BAFF mRNA levels in peripheral mononuclear cells
      were consistent with the protein levels. However, serum soluble BAFF levels were
      inter-individually different in each group. Stratified by renal function, it was
      found that cell-surface BAFF levels were significantly higher in those with
      abnormal renal function, compared with recipients with normal renal function (p <
      0.05). ELISA assay results showed that expression levels of cell surface BAFF
      were significantly correlated with anti-HLA I & II antibodies. These results
      indicate that BAFF may be involved in the development of graft-loss and
      influences the long-time outcome of kidney allograft, likely mediated by
      interfering with immune response.

PMID- 19118514
TI  - Expression of recombinant human FADD, preparation of its polyclonal antiserum and
      the application in immunoassays.
AB  - The wild-type human Fas-associated death domain (FADD) protein was expressed as a
      His-tag fusion protein in Escherichia coli. Recombinant FADD proteins were
      purified under the denatured condition. After denatured protein purification, it
      was refolded and obtained at a yield of about 23 mg/L. Purified FADD exhibited as
      a homogenous band corresponding to the molecular weight of 31 kDa. Immunization
      of rabbits against the refolded FADD protein was allowed the production of high
      titre polyclonal antiserum. This new polyclonal antibody could recognize
      recombinant FADD protein in Western blot. Immunoreactivity was also observed in
      immunofluorescence assay. The low cost polyclonal antiserum was applicable to
      extensive detection of FADD in various immunoassays.

PMID- 19118515
TI  - Hepatitis C virus infection downregulates the ligands of the activating receptor
      NKG2D.
AB  - Natural killer (NK) cells are a major component of the host innate immune defense
      against various pathogens. Several viruses, including hepatitis C virus (HCV),
      have developed strategies to evade the NK-cell response. In our study, we found
      HCV infection could trigger DNA damage response by both ataxia telangiectasia
      mutated (ATM) and ATM- and Rad3-related (ATR) pathways. Recent reports had
      revealed that NKG2D ligands (NK cell-activating ligands) were upregulated when a
      major DNA damage checkpoint pathway was activated. However, here we found that
      DNA damage response was activated but NKG2D ligands were downregulated upon HCV
      infection. Further studies showed that the protease NS3/4A of HCV which had been
      shown relation with immune invasion contributed to the reduced expression of
      NKG2D ligands. These findings provide a novel insight into the mechanisms evolved
      by HCV to escape from the NK cell response.

PMID- 19118516
TI  - Peptide induced demixing in PG/PE lipid mixtures: a mechanism for the specificity
      of antimicrobial peptides towards bacterial membranes?
AB  - Antimicrobial peptides attract a lot of interest as potential candidates to
      overcome bacterial resistance. So far, nearly all the proposed scenarios for
      their mechanism of action are associated with perforating and breaking down
      bacterial membranes after a binding process. In this study we obtained additional
      information on peptide induced demixing of bacterial membranes as a possible
      mechanism of specificity of antimicrobial peptides. We used DSC and FT-IR to
      study the influence of a linear and cyclic arginine- and tryptophan-rich
      antimicrobial peptide having the same sequence (RRWWRF) on the thermotropic phase
      transitions of lipid membranes. The cyclization of the peptide was found to
      enhance its antimicrobial activity and selectivity ( Dathe, M. Nikolenko, H.
      Klose, J. Bienert, M. Biochemistry 43 (2004) 9140-9150). A particular preference
      of the binding of the peptides to DPPG headgroups compared to other headgroups of
      negatively charged phospholipids, namely DMPA, DPPS and cardiolipin was observed.
      The main transition temperature of DPPG bilayers was considerably decreased by
      the bound peptides. The peptides caused a substantial down-shift of the
      transition of DPPG/DMPC. In contrast, they induced a demixing in DPPG/DPPE
      bilayers and led to the appearance of two peaks in the DSC curves indicating a
      DPPG-peptide-enriched domain and a DPPE-enriched domain. These results could be
      confirmed by FT-IR-spectroscopic measurements. We therefore propose that the
      observed peptide-induced lipid demixing in PG/PE-membranes could be a further
      specific effect of the antimicrobial peptides operating only on bacterial
      membranes, which contain appreciable amounts of PE and PG, and which could in
      principle also occur in liquid-crystalline membranes.

PMID- 19118517
TI  - The structure of detergent-resistant membrane vesicles from rat brain cells.
AB  - The size and the bilayer thickness of detergent-resistant membranes isolated from
      rat brain neuronal membranes using Triton X-100 or Brij 96 in buffers with or
      without the cations, K+/Mg2+ at a temperature of either 4 degrees C or 37 degrees
      C were determined by dynamic light scattering and small-angle neutron scattering.
      Regardless of the precise conditions used, isolated membrane preparations
      consisted of vesicles of approximately 100 to 200 nm diameter as determined by
      dynamic light scattering methods, equating to an area of the lipid based membrane
      microdomain size of 200 to 400 nm diameter. By means of small angle neutron
      scattering it was established that the average thickness of the bilayers of the
      complete population of detergent-resistant membranes was similar to that of the
      parental membrane at between 4.6 and 5.0 nm. Detergent-resistant membranes
      prepared using buffers containing K+/Mg2+ uniquely formed unilamellar vesicles
      while membranes prepared in the absence of K+/Mg2+ formed a mixture of uni- and
      oligolamellar structures indicating that the arrangement of the membrane differs
      from that observed in the presence of cations. Furthermore, the detergent
      resistant membranes prepared at 37 degrees C were slightly thicker than those
      prepared at 4 degrees C, consistent with the presence of a greater proportion of
      lipids with longer, more saturated fatty acid chains associated with the Lo
      (liquid-ordered) phase. It was concluded that the preparation of detergent
      resistant membranes at 37 degrees C using buffer containing cations abundant in
      the cytoplasm might more accurately reflect the composition of lipid rafts
      present in the plasma membrane under physiological conditions.

PMID- 19118519
TI  - Mechanistic role of ergosterol in membrane rigidity and cycloheximide resistance
      in Saccharomyces cerevisiae.
AB  - Mutants of Saccharomyces cerevisiae defective in the late steps of ergosterol
      biosynthesis are viable but accumulate structurally altered sterols within the
      plasma membrane. Despite the significance of pleiotropic abnormalities in the erg
      mutants, little is known about how sterol alterations mechanically affect the
      membrane structure and correlate with individual mutant phenotypes. Here we
      demonstrate that the membrane order and occurrence of voids are determinants of
      membrane rigidity and hypersensitivity to a drug. Among five ergDelta mutants,
      the erg2Delta mutant exhibited the most marked sensitivity to cycloheximide.
      Notably, measurement of time-resolved anisotropy indicated that the erg2Delta
      mutation decreased the membrane order parameter (S), and dramatically increased
      the rotational diffusion coefficient (D(w)) of 1-[4-(trimethylamino)pheny]-6
      phenyl-1,3,5-hexatriene (TMA-DPH) in the plasma membrane by 8-fold, providing
      evidence for the requirement of ergosterol for membrane integrity. The IC(50) of
      cycloheximide was closely correlated with S/D(w) in these strains, suggesting
      that the membrane disorder and increasing occurrence of voids within the plasma
      membrane synergistically enhance passive diffusion of cycloheximide across the
      membrane. Exogenous ergosterol partially restored the membrane properties in the
      upc2-1erg2Delta strain. In this study, we describe the ability of ergosterol to
      adjust the dynamic properties of the plasma membrane, and consider the relevance
      of drug permeability.

PMID- 19118518
TI  - Environmental tobacco smoke effects on lung surfactant film organization.
AB  - Adsorption of the clinical lung surfactants (LS) Curosurf or Survanta from
      aqueous suspension to the air-water interface progresses from multi-bilayer
      aggregates through multilayer films to a coexistence between multilayer and
      monolayer domains. Exposure to environmental tobacco smoke (ETS) alters this
      progression as shown by Langmuir isotherms, fluorescence microscopy and atomic
      force microscopy (AFM). After 12 h of LS exposure to ETS, AFM images of Langmuir
      Blodgett deposited films show that ETS reduces the amount of material near the
      interface and alters how surfactant is removed from the interface during
      compression. For Curosurf, ETS prevents refining of the film composition during
      cycling; this leads to higher minimum surface tensions. ETS also changes the
      morphology of the Curosurf film by reducing the size of condensed phase domains
      from 8-12 microm to approximately 2 microm, suggesting a decrease in the line
      tension between the domains. The minimum surface tension and morphology of the
      Survanta film are less impacted by ETS exposure, although the amount of material
      associated with the film is reduced in a similar way to Curosurf. Fluorescence
      and mass spectra of Survanta dispersions containing native bovine SP-B treated
      with ETS indicate the oxidative degradation of protein aromatic amino acid
      residue side chains. Native bovine SP-C isolated from ETS exposed Survanta had
      changes in molecular mass consistent with deacylation of the lipoprotein. Fourier
      Transform Infrared Spectroscopy (FTIR) characterization of the hydrophobic
      proteins from ETS treated Survanta dispersions show significant changes in the
      conformation of SP-B and SP-C that correlate with the altered surface activity
      and morphology of the lipid-protein film.

PMID- 19118520
TI  - Thiazolidinediones inhibit REG Ialpha gene transcription in gastrointestinal
      cancer cells.
AB  - REG (Regenerating gene) Ialpha protein functions as a growth factor for
      gastrointestinal cancer cells, and its mRNA expression is strongly associated
      with a poor prognosis in gastrointestinal cancer patients. We here demonstrated
      that PPARgamma-agonist thiazolidinediones (TZDs) inhibited cell proliferation and
      REG Ialpha protein/mRNA expression in gastrointestinal cancer cells. TZDs
      inhibited the REG Ialpha gene promoter activity, via its cis-acting element which
      lacked PPAR response element and could not bind to PPARgamma, in PPARgamma
      expressing gastrointestinal cancer cells. The inhibition was reversed by co
      treatment with a specific PPARgamma-antagonist GW9662. Although TZDs did not
      inhibit the REG Ialpha gene promoter activity in PPARgamma-non-expressing cells,
      PPARgamma overexpression in the cells recovered their inhibitory effect. Taken
      together, TZDs inhibit REG Ialpha gene transcription through a PPARgamma
      dependent pathway. The TZD-induced REG Ialpha mRNA reduction was abolished by
      cycloheximide, indicating the necessity of novel protein(s) synthesis. TZDs may
      therefore be a candidate for novel anti-cancer drugs for patients with
      gastrointestinal cancer expressing both REG Ialpha and PPARgamma.

PMID- 19118521
TI  - A steered molecular dynamics method with adaptive direction adjustments.
AB  - In this paper, a new steered molecular dynamics (SMD) method with adjusting
      pulling direction is proposed to search an optimum trajectory of ligand
      dissociation. A multiobjective model and a searching technique based on
      information entropy with multi-population are developed to optimize the pulling
      direction. The improved method has been used to dissociate the substrate-bound
      complex structure of cytochrome P450 3A4-metyrapone. A more favorable
      dissociation pathway can be gained. The results show that the new pathway
      obtained by the proposed method has less dissociation time, smaller rupture force
      and lower energy barrier than that by the conventional SMD.

PMID- 19118522
TI  - Th1 and Th2 cytokines are elevated in HCV-infected SVR(-) patients treated with
      interferon-alpha.
AB  - Interferon-alpha-based treatment is a standard therapy to cure hepatitis C virus
      infected patients. However, the reasons for the failure of interferon-alpha
      treatment in some patients have not been fully elucidated. We evaluated the
      differences in the expression levels of various cytokines among patients with and
      without sustained viral response (SVR). We found that the chemokines (MIG and IP
      10) and inflammation-related cytokines (IL-6) were transiently elevated in
      patients with SVR(+) before interferon-alpha treatment and in the early phase of
      treatment (week 2), indicating that these cytokines may be related to viral
      clearance. Furthermore, higher serum levels of Th1 and Th2 cytokines (IL-2, IL-4,
      IL-5, IL-10, tumor necrosis factor, and IFN-gamma) were observed in SVR(-) than
      in SVR(+) patients, indicating that they may be associated with ineffective anti
      HCV immune response. Our data revealed that the patterns of cytokines varied
      greatly between SVR(+) and SVR(-) patients before and after IFN-alpha treatment.

PMID- 19118523
TI  - Parvovirus capsid disorders cholesterol-rich membranes.
AB  - In this study canine parvovirus, CPV, was found to induce disorder in
      DPPC:cholesterol membranes in acidic conditions. This acidicity-induced
      fluidizing effect is suggested to originate from the N-terminus of the viral
      capsid protein VP1. In accordance with the model membrane studies, a fluidizing
      effect was seen also in the endosomal membranes during CPV infection implying an
      important functional role of the fluidization in the endocytic entry of the
      virus.

PMID- 19118524
TI  - Suppression of interleukin-6-induced C-reactive protein expression by FXR
      agonists.
AB  - C-reactive protein (CRP), a human acute-phase protein, is a risk factor for
      future cardiovascular events and exerts direct pro-inflammatory and pro
      atherogenic properties. The farnesoid X receptor (FXR), a member of the nuclear
      hormone receptor superfamily, plays an essential role in the regulation of
      enterohepatic circulation and lipid homeostasis. In this study, we report that
      two synthetic FXR agonists, WAY-362450 and GW4064, suppressed interleukin-6
      induced CRP expression in human Hep3B hepatoma cells. Knockdown of FXR by short
      interfering RNA attenuated the inhibitory effect of the FXR agonists and also
      increased the ability of interleukin-6 to induce CRP production. Furthermore,
      treatment of wild type C57BL/6 mice with the FXR agonist, WAY-362450, attenuated
      lipopolysaccharide-induced serum amyloid P component and serum amyloid A3 mRNA
      levels in the liver, whereas no effect was observed in FXR knockout mice. These
      data provide new evidence for direct anti-inflammatory properties of FXR.

PMID- 19118525
TI  - Tosylcyclonovobiocic acids promote cleavage of the hsp90-associated cochaperone
      p23.
AB  - The cochaperone p23 is required for the chaperoning cycle of hsp90 and to enhance
      the maturation of several client proteins. Tosylcyclonovobiocic acids (4TCNA and
      7TCNA) are potent analogs of novobiocin and induce cell cycle arrest, apoptosis
      and degradation of hsp90 client proteins in a panel of cancer cells. In this
      study, Western blotting shows that 4TCNA and 7TCNA triggered processing of the
      hsp90 cochaperone p23 in a dose-dependent manner. Small interfering RNA (siRNA)
      mediated reduction of p23 expression in MCF-7 breast cancer cells did not block
      4TCNA-induced caspase activation as assessed by the cleavage of PARP. This result
      indicates that 4TCNA-mediated cell death is a p23-independent process. In HT29
      colon cancer cells, 4TCNA and 7TCNA up-regulated GRP78 and GRP94 supporting
      involvement of ER stress in apoptosis.

PMID- 19118526
TI  - Activation of transgene expression in skeletal muscle by focused ultrasound.
AB  - To correlate thermal dose from focused ultrasound (FUS) with gene expression and
      tissue injury, a temperature plateau strategy was employed. Plasmids encoding
      luciferase gene under the control of hsp70B promoter were transfected into the
      right gastrocnemius muscle in a rat via electroporation. One day after
      transfection, hind limbs were treated with 3.3-MHz focused ultrasound, using one
      of four different temperature plateaus with spatial-peak time-average focal
      temperatures (T(SPTA)) of 46 degrees C, 48 degrees C, 51 degrees C and 62 degrees
      C. The treatment duration at the plateau temperature was varied from 0 to 30s.
      Gene expression was analyzed in vivo one day following FUS treatment, and H&E
      staining was employed to assess tissue injury. Gene activation and tissue damage
      correlated closely with thermal dose. The highest level of gene activation was
      induced by FUS at T(SPTA)=51 degrees C for 20s, which was found to be
      statistically equivalent to that produced by water-bath hyperthermia.

PMID- 19118527
TI  - Hydrostatic pressure promotes Wnt10b and Wnt4 expression dependent and
      independent on ERK signaling in early-osteoinduced MSCs.
AB  - Recent publications have shown that mechanical stress can regulate the direction
      of stem cell differentiation. The exact mechanobiological effects of pressure on
      initial osteodifferentiation have not been determined. Here, we show that ERK
      signaling participates in early osteodifferentiation and plays a positive but non
      critical role in mechanotransduction, whereas p38 MAPK is not involved in this
      process. Moreover, our findings provide evidence that in response to both types
      of pressure with high sensitivity, Wnt10b mRNA is ERK-dependent whereas Wnt4 mRNA
      is upregulated by treatment of the inhibitor of ERK signaling. The findings
      suggest novel mechanisms of the initial biological responses of bone remodeling
      and regeneration upon mechanical stimuli.

PMID- 19118528
TI  - Simple ortho- and para-hydroquinones as compounds neuroprotective against
      oxidative stress in a manner associated with specific transcriptional activation.
AB  - Electrophilic compounds protect neurons through the activation of the Keap1/Nrf2
      pathway and the induction of phase-2 enzymes [T. Satoh, S.A. Lipton, Redox
      regulation of neuronal survival by electrophilic compounds, Trends Neurosci. 30
      (2007) 38-45; T. Satoh, S. Okamoto, J. Cui, Y. Watanabe, K. Furuta, M. Suzuki, K.
      Tohyama, S.A. Lipton, Activation of the Keap1/Nrf2 pathway for neuroprotection by
      electrophilic phase II inducers. Proc. Natl. Acad. Sci. USA 103 (2006) 768-773].
      Hydroquinone-type electrophilic compounds such as tert-butyl hydroquinone (TBHQ)
      and carnosic acid (CA) have attracted special attention, because the oxidative
      conversion of "hydroquinone" to "quinone" is essential for the transcriptional
      activation of the above-mentioned enzymes [T. Satoh, K. Kosaka, K. Itoh, A.
      Kobayashi, M. Yamamoto, Y. Shimojo, C. Kitajima, J. Cui, J. Kamins, S. Okamoto,
      T. Shirasawa, S.A. Lipton, Carnosic acid, a catechol-type electrophilic compound,
      protect neurons both in vitro and in vivo through activation of the Keap1/Nrf2
      pathway via S-alkylation of specific cysteine, J. Neurochem. 104 (2008) 1161
      1131; A.D. Kraft, D.A. Johnson, J.A. Johnson, Nuclear factor E2-related factor 2
      dependent antioxidant response element activation by tert-butylhydroquinone and
      sulforaphane occurring preferentially in astrocytes conditions neurons against
      oxidative insult, J. Neurosci. 24 (2004) 1101-1112]. In the present study, we
      examined the relationship between electrophilicity and the protective effects
      afforded by electrophilic compounds. Electrophilicity was assessed in terms of
      the ability of a compound to bind to a cysteine on bovine serum albumin, by which
      we found that neuroprotective hydroquinones [TBHQ (para-) and CA (ortho-)] had
      distinctive patterns of cysteine binding compared with other electrophilic
      compounds. Further, we found that isomers of simple ortho- and para-hydroquinones
      such as 2-methylhydroquinone (para-) and 4-methyl-catechol (ortho-) [not in
      abstract] had similar properties of cysteine binding as TBHQ and CA, which
      compounds were associated with the transcriptional activation and an increase in
      the level of reduced glutathione. These results suggest that para- and ortho
      dihydroquinones may be neuroprotective compounds active against oxidative stress.

PMID- 19118530
TI  - Proportion between wild-type and mutant protein in truncated compared to full
      length ATTR: an analysis on transplanted transthyretin T60A amyloidosis patients.
AB  - Familial ATTR amyloidosis is caused by point mutations in the transthyretin gene.
      The clinical manifestations are highly varied but polyneuropathy and/or
      cardiomyopathy are generally the main symptoms. The amyloid fibrils can either be
      composed of only intact ATTR molecules or intact together with fragmented ATTR
      species. As plasma TTR is almost exclusively synthesized in the liver, liver
      transplantation is performed in order to eliminate the mutant plasma TTR. The
      procedure has shown best results among patients with the V30M mutation, while a
      rapid continued cardiac deposition of wild-type (wt) TTR has been seen for many
      other mutations. In this paper we investigated the proportion of wtATTR in two
      TTRT60A patients that underwent liver transplantation; one patient died 3 weeks
      after surgery, the other patient survived for 12 months. As the role of
      fragmented TTR species in the pathogenesis is far from understood, we
      investigated the proportion of wt in these species separately to the full-length
      molecules, which has not been done before in transplanted patients. The results
      show a higher proportion of wtTTR in the 12-months-surviving patient than the 3
      weeks-surviving patient, but interestingly this difference in wt proportion is
      mainly seen among the full-length, and not the fragmented, molecules.

PMID- 19118529
TI  - Identification of novel targets for PGC-1alpha and histone deacetylase inhibitors
      in neuroblastoma cells.
AB  - Recent evidence suggests that the transcriptional coactivator peroxisome
      proliferator activated receptor gamma coactivator 1alpha (PGC-1alpha) is involved
      in the pathology of Huntington's Disease (HD). While animals lacking PGC-1alpha
      express lower levels of genes involved in antioxidant defense and oxidative
      phosphorylation in the brain, little is known about other targets for PGC-1alpha
      in neuronal cells and whether there are ways to pharmacologically target PGC
      1alpha in neurons. Here, PGC-1alpha overexpression in SH-SY5Y neuroblastoma cells
      upregulated expression of genes involved in mitochondrial function, glucose
      transport, fatty acid metabolism, and synaptic function. Overexpression also
      decreased vulnerability to hydrogen peroxide-induced cell death and caspase 3
      activation. Treatment of cells with the histone deacetylase inhibitors (HDACi's)
      trichostatin A and valproic acid upregulated PGC-1alpha and glucose transporter 4
      (GLUT4). These results suggest that PGC-1alpha regulates multiple pathways in
      neurons and that HDACi's may be good candidates to target PGC-1alpha and GLUT4 in
      HD and other neurological disorders.

PMID- 19118531
TI  - Gene expression profiles of dynamically compressed single chondrocytes and
      chondrons.
AB  - A chondrocyte produces a hydrated pericellular matrix (PCM); together they form a
      chondron. Previous work has shown that the presence of the PCM influences the
      biological response of chondrocytes to loading. The objective of this study was
      to determine the gene expression profiles of enzymatically isolated single
      chondrocytes and chondrons in response to dynamic compression. Cartilage specific
      extracellular matrix components and transcription factors were examined.
      Following dynamic compression, chondrocytes and chondrons showed variations in
      gene expression profiles. Aggrecan, Type II collagen and osteopontin gene
      expression were significantly increased in chondrons. Lubricin gene expression
      decreased in both chondrons and chondrocytes. Dynamic compression had no effect
      on SOX9 gene expression. Our results demonstrate a clear role for the PCM in
      interfacing the mechanical signalling in chondrocytes in response to dynamic
      compression. Further investigation of single chondrocytes and chondrons from
      different zones within articular cartilage may further our understanding of
      cartilage mechanobiology.

PMID- 19118532
TI  - Mechanisms of LPS-induced CD40 expression in human peripheral blood monocytic
      cells.
AB  - CD40 plays important roles in cell-mediated and humoral immune responses. In this
      study, we explored mechanisms underlying lipopolysaccharide (LPS)-induced CD40
      expression in purified human peripheral blood monocytic cells (PBMCs) from
      healthy volunteers. Exposure to LPS induced increases in CD40 mRNA and protein
      expression on PBMCs. LPS stimulation caused IkappaBalpha degradation. Inhibition
      of NFkappaB activation abrogated LPS-induced CD40 expression. LPS stimulation
      also resulted in phosphorylation of mitogen-activated protein kinases, however,
      only Jun N-terminal kinase (JNK) was partially involved in LPS-induced CD40
      expression. In addition, LPS exposure resulted in elevated interferon gamma
      (IFNgamma) levels in the medium of PBMCs. Neutralization of IFNgamma and IFNgamma
      receptor using specific antibodies blocked LPS-induced CD40 expression by 44% and
      37%, respectively. In summary, LPS-induced CD40 expression on human PBMCs through
      activation of NFkappaB and JNK, and partially through the induction of IFNgamma
      production.

PMID- 19118533
TI  - Human selenium binding protein-1 (hSP56) interacts with VDU1 in a selenium
      dependent manner.
AB  - Reduced expression of the 56-kDa human selenium binding protein-1 (hSP56) has
      been reported in many types of human malignancies, including prostate, lung,
      ovarian, thyroid and colorectal cancers. hSP56 also has been implicated in
      selenium-dependent cell growth inhibition. However, the molecular basis of
      hSP56's function has not been elucidated. In the present study, we identified von
      Hippel-Lindau protein (pVHL)-interacting deubiquitinating enzyme 1 (VDU1) as a
      protein partner of hSP56 using a yeast two-hybrid screen. The interaction between
      hSP56 and VDU1 was confirmed by yeast two-hybrid analysis and in vitro binding
      experiments. hSP56 and VDU1 co-localized in the perinuclear region of LNCaP human
      prostate cancer cells. The full-length VDU1 specifically interacted with a
      selenium-replete form of hSP56. We also demonstrate stable incorporation of
      selenium into hSP56, in a mode distinct from conventional selenocysteine
      containing selenoproteins. These findings suggest that hSP56 may play a role in
      ubiquitination/deubiquitination-mediated protein degradation pathways in a
      selenium-dependent manner.

PMID- 19118534
TI  - Modulations of AtGSTF10 expression induce stress tolerance and BAK1-mediated cell
      death.
AB  - Glutathione-S-transferases are essential proteins involved in cellular
      detoxification. The expression of GSTs has been studied extensively under various
      environmental stressors including xenobiotics. Here, we have isolated AtGST10,
      one of the phi classes of AtGSTs on the basis of its interaction with BAK1 in a
      yeast two-hybrid screen. BAK1 is an LRR-RLK, acting in both brassinosteroid
      signaling and plant defense responses. We found that AtGSTF10 binds to BAK1
      through its N-terminal domain. AtGSTF10 is expressed ubiquitously in plant
      tissues, and the endogenous transcript level of AtGSTF10 was not induced by plant
      growth regulators or abiotic stressors, except drought, unlike other GSTs.
      Overexpression of AtGSTF10 conferred higher tolerance to salt and disturbed redox
      status of transgenic plants. The down-regulation of AtGSTF10 produced by RNA
      interference caused reduced tolerance to abiotic stress and an accelerated
      senescence of transformants, indicating that AtGSTF10 is involved in stress
      tolerance and the BAK1-mediated spontaneous cell death signaling pathway in
      Arabidopsis.

PMID- 19118535
TI  - Increased densities of monocarboxylate transporter MCT1 after chronic
      hyperglycemia in rat brain.
AB  - The brain is capable of taking up monocarboxylates as energy substrates. Under
      physiological conditions, plasma levels of monocarboxylates are very low and
      glucose is the primary energy substrate in brain metabolism. However, given
      conditions such as hyperglycemia and ketosis, levels of circulating
      monocarboxylates such as lactate and pyruvate are elevated. Previous studies
      reported an increased expression of monocarboxylate transporter MCT1 in brain
      following ketotic diet. The major aim of the present study was to answer the
      question whether chronic hyperglycemia is likewise sufficient to change local
      densities of MCT1 in the brain. Moreover, chronic hyperglycemia increases local
      cerebral glucose utilization (LCGU) in particular brain areas. Glucose hereby
      enters the brain parenchyma via glucose transporters and is partially metabolised
      by astrocytes, which then release lactate to meet the energetic demands of
      surrounding neurons. Streptozotocin was given intravenously to induce chronic
      hyperglycemia and local densities of MCT1 were measured by immunoautoradiographic
      methods in cryosections of rat brains. The density of monocarboxylate transporter
      MCT1 was significantly increased in 10 of 24 brain structures investigated
      (median increase 11.7+/-3.4 %). Immunocytochemical stainings of these
      substructures revealed an expression of MCT1 within endothelial cells and
      astrocytes. A comparison of MCT1 densities with LCGU measured in a previous study
      under normo- and hyperglycemic conditions revealed a partial correlation between
      both parameters and under both conditions. Four out of 10 brain areas, which
      showed a significant increase in MCT1 density due to hyperglycemia, also showed a
      significant increase in LCGU. In summary, our data show that chronic
      hyperglycemia induces a moderate increase of local and global density of MCT1 in
      several brain structures. However, in terms of brain topologies and substructures
      this phenomenon did only partially match with increased LCGU. It is concluded
      that MCT1 transporters were up-regulated during chronic hyperglycemia at the
      level of brain substructures and independently of LCGU.

PMID- 19118536
TI  - Effects of perinatal asphyxia on the neurobehavioral and retinal development of
      newborn rats.
AB  - Perinatal asphyxia during delivery produces long-term deficits and represents a
      major problem in both neonatal and pediatric care. Several morphological,
      biochemical and behavioral changes have been described in rats exposed to
      perinatal asphyxia. The aim of the present study was to evaluate how perinatal
      asphyxia affects the complex early neurobehavioral development and retinal
      structure of newborn rats. Asphyxia was induced in ready-to-deliver mothers by
      removing the pups by cesarian section after 15 min of asphyxia. Somatic and
      neurobehavioral development was tested daily during the first 3 weeks, and motor
      coordination tests were performed on postnatal weeks 3-5. After completion of the
      testing procedure, retinas were removed for histological analysis. We found that
      in spite of the fast catch-up-growth of asphyctic pups, nearly all examined
      reflexes were delayed by 1-4 days: negative geotaxis, sensory reflexes, righting
      reflexes, development of fore- and hindlimb grasp and placing, gait and auditory
      startle reflexes. Time to perform negative geotaxis, surface righting and gait
      reflexes was significantly longer during the first few weeks in asphyctic pups.
      Among the motor coordination tests, a markedly weaker performance was observed in
      the grid walking and footfault test and in the walk initiation test. Retinal
      structure showed severe degeneration in the layer of the photoreceptor and
      bipolar cell bodies. In summary, our present study provided a detailed
      description of reflex and motor development following perinatal asphyxia, showing
      that asphyxia led to a marked delay in neurobehavioral development and a severe
      retinal degeneration.

PMID- 19118537
TI  - Brain structural differences associated with the behavioural phenotype in
      children with Williams syndrome.
AB  - BACKGROUND: We investigated structural brain morphology of intellectually
      disabled children with Williams (WS) syndrome and its relationship to the
      behavioural phenotype. METHODS: We compared the neuroanatomy of 15 children (mean
      age:13+/-2) with WS and 15 age/gender-matched healthy children using a manual
      region-of-interest analysis to measure bulk (white+grey) tissue volumes and
      unbiased fully-automated voxel-based morphometry to assess differences in
      grey/white matter throughout the brain. Ratings of abnormal behaviours were
      correlated with brain structure. RESULTS: Compared to controls, the brains of
      children with WS had a decreased volume of the right parieto-occipital regions
      and basal ganglia. We identified reductions of grey matter of the parieto
      occipital regions, left putamen/globus pallidus and thalamus; and in white matter
      of the basal ganglia and right posterior cingulate gyrus. In contrast,
      significant increases of grey matter were identified in the frontal lobes,
      anterior cingulate gyrus, left temporal lobe, and of white matter bilaterally in
      the anterior cingulate. Inattention in WS was correlated with volumetric
      differences in the frontal lobes, caudate nucleus and cerebellum, and
      hyperactivity was related to differences in the left temporal and parietal lobes
      and cerebellum. Finally, ratings of peer problems were related to differences in
      the temporal lobes, right basal ganglia and frontal lobe. CONCLUSIONS: In one of
      the first studies of brain structure in intellectually disabled children with WS
      using voxel-based morphometry, our findings suggest that this group has specific
      differences in grey/white matter morphology. In addition, it was found that
      structural differences were correlated to ratings of inattention, hyperactivity
      and peer problems in children with WS.

PMID- 19118538
TI  - NMDA preconditioning and neuroprotection in vivo: delayed onset of kainic acid
      induced neurodegeneration and c-Fos attenuation in CA3a neurons.
AB  - Intraventricular (i.c.v.) kainic acid (KA) causes an acute excitotoxic lesion to
      the CA3 region of rodent hippocampus. Recent evidence implicated c-fos gene in
      regulating neuron survival and death following an excitotoxic insult. In this
      study we attempted to prevent KA-induced damage in CA3 neurons with NMDA
      preconditioning, which produced a marked expression of c-fos in the hippocampus.
      NMDA (0.6-6 microg, i.c.v.) was injected to anesthetized rats alone or 1 h before
      KA (0.15 microg, i.c.v.). Following KA injection, vibratome sections were
      processed for immunohistochemistry/electron microscopy. c-Fos and Nissl staining
      were used to estimate the extent of neuronal excitation and damage, respectively.
      Quantitative evaluation of c-Fos-labeled cells showed significantly less c-Fos in
      CA3a than in neighboring CA3b and CA2 from 1 to 4 h after KA alone. Attenuation
      of expressed c-Fos in CA3a was accompanied by damage of neurons with more
      apoptotic than necrotic signs. NMDA preconditioning elevated CA3a c-Fos
      expression and at 1 and 2 h exceeded markedly that after KA alone. However, at 4
      h after KA, NMDA-preconditioned c-Fos induction in CA3a diminished to the same
      level as that seen after KA alone. The onset of neuronal degeneration was delayed
      in similar way. While NMDA-induced c-Fos expression in CA3a could be blocked by
      MK-801 completely, MK-801 and CNQX were both without significant effect on KA
      induced c-Fos expression and neuronal damage. In conclusion, inhibition of c-Fos
      expression and onset of neuronal damage in CA3a following icv KA injection might
      be transiently delayed by i.c.v. NMDA preconditioning.

PMID- 19118539
TI  - Strategy for sensitive and specific detection of molecular forms of PSA based on
      2DE and kinetic analysis: a step towards diagnosis of prostate cancer.
AB  - BACKGROUND: Prostate specific antigen (PSA) present in human seminal fluid exists
      in many isoforms due to different sequence, glycosylation pattern and polypeptide
      length. Its presence in various stages of cancer has already been reported.
      METHODS: We identified 8 forms of PSA followed by purification of 3 forms. We
      compared their binding affinities to designed synthetic peptides, by using
      surface plasmon resonance (SPR). PSA forms were purified using various
      chromatographic procedures and characterized by 2D gel electrophoresis (2DE),
      matrix-assisted laser desorption/ionization-time of flight mass spectrometry
      (MALDI-TOF MS) and sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS
      PAGE). RESULTS: The heterogeneity of purified PSA was demonstrated by 2DE
      analysis. The peptides were designed on the basis of cleavage map of insulin-like
      growth factor binding protein 3 (IGFBP-3) subsequently, these peptides showed the
      binding affinities in the range of 10(-5) to 10(-12) M. Out of 7 peptides, VLLH
      showed maximum affinity to intact PSA, while FLSYK showed maximum affinity to
      cleaved forms of PSA. On the other hand, FLSYK in the presence of zinc showed
      higher affinity to intact PSA. These peptides showed higher affinity to PSA
      compared to zinc, which is a known inhibitor of PSA. CONCLUSIONS: This study
      reports purification and characterization of 3 forms of PSA simultaneously.
      Furthermore, we have reported specific peptides for different forms of PSA which
      are either responsible for prostate cancer (PCa) or benign prostatic hyperplasia
      (BPH). Our study aids the existing information on categorizing the molecular
      heterogeneity of PSA.

PMID- 19118540
TI  - Evaluation of high-resolution melting analysis for screening the LDL receptor
      gene.
AB  - OBJECTIVES: High-resolution melting analysis has been validated for screening
      several genes of clinical significance. We evaluated whether it would be useful
      for detecting mutations in the LDL receptor gene (LDLR). DESIGN AND METHODS: We
      analysed 60 samples heterozygous for different LDLR sequence variants, and
      compared the melting curves to those of the corresponding homozygous normal
      amplicons to assess whether they would be detected in a mutation scanning screen
      using melting analysis. RESULTS: Although six mutations in exon 4 did not yield
      usable melting data, 96% (52/54) of the other variants were detected by the
      melting analysis, while two variants were poorly resolved. CONCLUSIONS: Melting
      analysis is a rapid and sensitive mutation scanning technique, but is not
      suitable for some GC-rich amplicons such as LDLR exon 4, or exons with high
      frequencies of benign polymorphisms which would require follow-up DNA sequencing.
      We developed a successful strategy which combines melting analysis with direct
      sequencing of problematic amplicons.

PMID- 19118541
TI  - Intracellular ice formation in yeast cells vs. cooling rate: predictions from
      modeling vs. experimental observations by differential scanning calorimetry.
AB  - To survive freezing, cells must not undergo internal ice formation during
      cooling. One vital factor is the cooling rate. The faster cells are cooled, the
      more their contents supercool, and at some subzero temperature that supercooled
      cytoplasm will freeze. The question is at what temperature? The relation between
      cooling rate and cell supercooling can be computed. Two important parameters are
      the water permeability (Lp) and its temperature dependence. To avoid
      intracellular ice formation (IIF), the supercooling must be eliminated by
      dehydration before the cell cools to its ice nucleation temperature. With an
      observed nucleation temperature of -25 degrees C, the modeling predicts that IIF
      should not occur in yeast cooled at <20 degrees C/min and it should occur with
      near certainty in cells cooled at >or=30 degrees C/min. Experiments with
      differential scanning calorimetry (DSC) confirmed these predictions closely. The
      premise with the DSC is that if there is no IIF, one should see only a single
      exotherm representing the freezing of the external water. If IIF occurs, one
      should see a second, lower temperature exotherm. A further test of whether this
      second exotherm is IIF is whether it disappears on repeated freezing. IIF
      disrupts the plasma membrane; consequently, in a subsequent freeze cycle, the
      cell can no longer supercool and will not exhibit a second exotherm. This proved
      to be the case at cooling rates >20 degrees C/min.

PMID- 19118542
TI  - The HLH protein Extramacrochaetae is required for R7 cell and cone cell fates in
      the Drosophila eye.
AB  - Notch signaling is one of the most important pathways in development and
      homeostasis, and is altered in multiple pathologies. Study of Drosophila eye
      development shows that Notch signaling depends on the HLH protein
      Extramacrochaetae. Null mutant clones show that extramacrochaetae is required for
      multiple aspects of eye development that depend on Notch signaling, including
      morphogenetic furrow progression, differentiation of R4, R7 and cone cell types,
      and rotation of ommatidial clusters. Detailed analysis of R7 and cone cell
      specification reveals that extramacrochaetae acts cell autonomously and
      epistatically to Notch, and is required for normal expression of bHLH genes
      encoded by the E(spl)-C which are effectors of most Notch signaling. A model is
      proposed in which Extramacrochaetae acts in parallel to or as a feed-forward
      regulator of the E(spl)-Complex to promote Notch signaling in particular cellular
      contexts.

PMID- 19118543
TI  - Functions of Fyn kinase in the completion of meiosis in mouse oocytes.
AB  - Oocyte maturation invokes complex signaling pathways to achieve cytoplasmic and
      nuclear competencies for fertilization and development. The Src-family kinases
      FYN, YES and SRC are expressed in mammalian oocytes but their function during
      oocyte maturation remains an open question. Using chemical inhibitor, siRNA
      knockdown, and gene deletion strategies the function of Src-family kinases was
      evaluated in mouse oocytes during maturation under in vivo and in vitro
      conditions. Suppression of Src-family as a group with SKI606 greatly reduced
      meiotic cell cycle progression to metaphase-II. Knockdown of FYN kinase
      expression after injection of FYN siRNA resulted in an approximately 50%
      reduction in progression to metaphase-II similar to what was observed in oocytes
      isolated from FYN (-/-) mice matured in vitro. Meiotic cell cycle impairment due
      to a Fyn kinase deficiency was also evident during oocyte maturation in vivo
      since ovulated cumulus oocyte complexes collected from FYN (-/-) mice included
      immature metaphase-I oocytes (18%). Commonalities in meiotic spindle and
      chromosome alignment defects under these experimental conditions demonstrate a
      significant role for Fyn kinase activity in meiotic maturation.

PMID- 19118544
TI  - Cortical deficiency of laminin gamma1 impairs the AKT/GSK-3beta signaling pathway
      and leads to defects in neurite outgrowth and neuronal migration.
AB  - Laminins have dramatic and varied actions on neurons in vitro. However, their in
      vivo function in brain development is not clear. Here we show that knockout of
      laminin gamma1 in the cerebral cortex leads to defects in neuritogenesis and
      neuronal migration. In the mutant mice, cortical layer structures were disrupted,
      and axonal pathfinding was impaired. During development, loss of laminin
      expression impaired phosphorylation of FAK and paxillin, indicating defects in
      integrin signaling pathways. Moreover, both phosphorylation and protein levels of
      GSK-3beta were significantly decreased, but only phosphorylation of AKT was
      affected in the mutant cortex. Knockout of laminin gamma1 expression in vitro,
      dramatically inhibited neurite growth. These results indicate that laminin
      regulates neurite growth and neuronal migration via integrin signaling through
      the AKT/GSK-3beta pathway, and thus reveal a novel mechanism of laminin function
      in brain development.

PMID- 19118545
TI  - Transcriptional regulation of NF-kappaB by ring type decoy oligodeoxynucleotide
      in an animal model of nephropathy.
AB  - Inflammation of the tubulointerstitial compartment, leading to fibrosis, is a
      major factor in the progressive loss of renal function in a wide variety of
      kidney diseases. In order to develop a therapeutic approach for nephropathy, we
      examined the simultaneous inhibition of transcription factor nuclear factor
      kappaB (NF-kappaB), which is responsible for a wide range of cellular processes,
      especially inflammation, in a mouse model of unilateral ureteral obstruction. In
      this study, we employed a ring-type NF-kappaB (R-NF-kappaB) decoy
      oligodeoxynucleotide (ODN), containing consensus promoter sequences of NF-kappaB.
      This R-NF-kappaB decoy ODN is more highly resistant to degradation by nucleases
      than is the current phosphothiolated double stranded NF-kappaB decoy ODN. The
      inhibitory effect of R-NF-kappaB decoy ODN on nephropathy was confirmed by
      molecular and histological examinations. In addition, treatment with R-NF-kappaB
      decoy ODN reduced the activities of inflammatory cytokines, such as tumor
      necrosis factor-alpha and interleukin-1beta. Interestingly, the treatment with R
      NF-kappaB decoy ODN also suppressed the gene expression of transforming growth
      factor-beta1 and fibronectin, resulting in the inhibition of fibrotic changes.
      These results suggest that the inhibition of NF-kappaB using R-NF-kappaB decoy
      ODN has potential therapeutic application in the prevention of renal fibrosis.

PMID- 19118547
TI  - Ankyrin repeat domain 28 (ANKRD28), a novel binding partner of DOCK180, promotes
      cell migration by regulating focal adhesion formation.
AB  - DOCK180 is a guanine exchange factor of Rac1 originally identified as a protein
      bound to an SH3 domain of the Crk adaptor protein. DOCK180 induces tyrosine
      phosphorylation of p130(Cas), and recruits the Crk-p130(Cas) complex to focal
      adhesions. To understand the role of DOCK180 in cell adhesion and migration, we
      searched for DOCK180-binding proteins with a nano-LC/MS/MS system, and identified
      ANKRD28, a protein that contains twenty-six ankyrin domain repeats. Knockdown of
      ANKRD28 by RNA interference reduced the velocity of migration of HeLa cells,
      suggesting that this protein plays a physiologic role in the DOCK180-Rac1
      signaling pathway. Furthermore, knockdown of ANKRD28 was found to alter the
      distribution of focal adhesion proteins such as Crk, paxillin, and p130(Cas). On
      the other hand, expression of ANKRD28, p130(Cas), Crk, and DOCK180 induced hyper
      phosphorylation of p130(Cas), and impaired detachment of the cell membrane during
      migration. Consequently, cells expressing ANKRD28 exhibited multiple long
      cellular processes. ANKRD28 associated with DOCK180 in an SH3-dependent manner
      and competed with ELMO, another protein bound to the SH3 domain of DOCK180. In
      striking contrast to ANKRD28, overexpression of ELMO induced extensive
      lamellipodial protrusion around the entire circumference. These data suggest that
      ANKRD28 specifies the localization and the activity of the DOCK180-Rac1 pathway.

PMID- 19118546
TI  - Functional determinants of ras interference 1 mutants required for their
      inhbitory activity on endocytosis.
AB  - In this study, we initiated experiments to address the structure-function
      relationship of Rin1. A total of ten substitute mutations were created, and their
      effects on Rin1 function were examined. Of the ten mutants, four of them (P541A,
      E574A, Y577F, T580A) were defective in Rab5 binding, while two other Rin1 mutants
      (D537A, Y561F) partially interacted with Rab5. Mutations in several other
      residues (Y506F, Y523F, T572A, Y578F) resulted in partial loss of Rab5 function.
      Biochemical studies showed that six of them (D537A, P541A, Y561F, E574A, Y577F,
      T580A) were unable to activate Rab5 in an in vitro assay. In addition, Rin1:
      D537A and Rin1: Y561F mutants showed dominant inhibition of Rab5 function.
      Consistent with the biochemical studies, we observed that these two Rin1 mutants
      have lost their ability to stimulate the endocytosis of EGF, form enlarged Rab5
      positive endosomes, or support in vitro endosome fusion. Based on these data, our
      results showed that mutations in the Vps9 domain of Rin1 lead to a loss-of
      function phenotype, indicating a specific structure-function relationship between
      Rab5 and Rin1.

PMID- 19118548
TI  - Hypoxia/reoxygenation induces CTGF and PAI-1 in cultured human retinal pigment
      epithelium cells.
AB  - Early age-related macular degeneration (AMD) is characterized by thickening of
      Bruch's membrane due to the accumulation of extracellular matrix (ECM). This
      finding could be related to hypoxia of the retinal pigment epithelium (RPE). In
      the present study, we investigated the effects of hypoxia and reoxygenation on
      the expression of connective tissue growth factor (CTGF), plasminogen activator
      inhibitor-1 (PAI-1), collagen type IV (Col IV) and fibronectin (Fn) in cultured
      human RPE cells. Cultured human RPE cells were kept for 12-36h under hypoxic
      conditions (1% O(2)). Reoxygenation was conducted for 24h. Hypoxia-mediated CTGF
      and PAI-1 expression were analyzed by using immunohistochemistry, Northern and
      Western blot analysis. Actinomycin D was added to examine whether hypoxia induces
      the transcription of CTGF and PAI-1 mRNA. Furthermore, cells were transfected
      with siRNA against hypoxia-inducible factor-1alpha (HIF-1alpha) and kept under
      hypoxic conditions. The effects of antioxidants on hypoxia/reoxygenation-mediated
      CTGF and PAI-1 expression were tested by real-time PCR analysis. Production of
      Col IV and Fn were investigated by real-time PCR and Western blot analysis. Both
      hypoxia and hypoxia/reoxygenation increased the expression of CTGF, PAI-1, Col IV
      and Fn. Actinomycin D prevented the new transcription of CTGF and PAI-1 mRNA by
      hypoxia. Using siRNA against HIF-1alpha, the hypoxia-mediated increase of CTGF
      and PAI-1 was inhibited. Antioxidants attenuated the reoxygenation-mediated
      increase of CTGF and PAI-1. The process of hypoxia/reoxygenation in the RPE may
      lead to an increase of ECM in the RPE and thus may contribute to the accumulation
      of ECM in Bruch's membrane.

PMID- 19118549
TI  - Environmental enrichment enhances cellular plasticity in transgenic mice with
      Alzheimer-like pathology.
AB  - Alzheimer's disease (AD) is accompanied by hippocampal neuronal loss and abnormal
      neurogenesis, both of which probably contributing to AD-related cognitive
      deficits. Mounting evidence indicates that cognitive and physical stimulation
      provided by environmental enrichment improves neurogenesis in healthy animals and
      counteracts beta-amyloid pathology in mouse models of AD. Here, we hypothesized
      that environmental enrichment has also an impact on hippocampal neurogenesis in
      mice with AD-like pathology. Therefore, TgCRND8 mice and wild type littermates
      were either housed under standard conditions or in an enriched environment for 4
      months. Standard housed TgCRND8 mice revealed diminished hippocampal cell
      proliferation and reduced number of mature newborn neurons compared to wild type
      littermates under the same housing condition. However, environmental enrichment
      reversed this genotype effect. Here, we show that cognitive and physical
      stimulation is capable of increasing the number of newborn mature hippocampal
      neurons in transgenic mice to wild type levels. Moreover, the expression of
      various plasticity associated molecules was enhanced in transgenic mice due to
      enriched housing. This study identifies that environmental enrichment improves
      diminished cellular plasticity in AD brain, probably enhancing the brain capacity
      to better compensate for neurodegeneration.

PMID- 19118550
TI  - Secondary degeneration of the optic nerve following partial transection: the
      benefits of lomerizine.
AB  - Secondary degeneration is a form of 'bystander' damage that can affect neural
      tissue both nearby and remote from an initial injury. Partial optic nerve
      transection is an excellent model in which to unequivocally differentiate events
      occurring during secondary degeneration from those resulting from primary CNS
      injury. We analysed the primary injury site within the optic nerve (ON) and
      intact areas vulnerable to secondary degeneration. Areas affected by the primary
      injury showed morphological disruption, loss of beta-III tubulin axonal staining,
      reduced myelinated axon density, greater proteoglycan expression (phosphacan),
      increased microglia and macrophage numbers and increased oxidative stress.
      Similar, but less extreme, changes were seen in areas of the optic nerve
      undergoing secondary degeneration. The CNS-specific L- and T-type calcium channel
      blocker lomerizine alleviated some of the changes in areas vulnerable to
      secondary degeneration. Lomerizine reduced morphological disruption, oxidative
      stress and phosphacan expression, and limited early increases in macrophage
      numbers. However, lomerizine failed to prevent progressive de-myelination of ON
      axons. Within the retina, secondary retinal ganglion cell (RGC) death was
      significant in areas vulnerable to secondary degeneration. Lomerizine protected
      RGCs from secondary death at 4 weeks but did not fully restore behavioural
      function (optokinetic nystagmus). We conclude that blockade of calcium channels
      is neuroprotective and limits secondary degenerative changes following CNS
      injury. However such an approach may need to be combined with other treatments to
      ensure long-term maintenance of full visual function.

PMID- 19118551
TI  - Experimental and theoretical characterization of the voltage distribution
      generated by deep brain stimulation.
AB  - Deep brain stimulation (DBS) is an established therapy for the treatment of
      Parkinson's disease and shows great promise for numerous other disorders. While
      the fundamental purpose of DBS is to modulate neural activity with electric
      fields, little is known about the actual voltage distribution generated in the
      brain by DBS electrodes and as a result it is difficult to accurately predict
      which brain areas are directly affected by the stimulation. The goal of this
      study was to characterize the spatial and temporal characteristics of the voltage
      distribution generated by DBS electrodes. We experimentally recorded voltages
      around active DBS electrodes in either a saline bath or implanted in the brain of
      a non-human primate. Recordings were made during voltage-controlled and current
      controlled stimulation. The experimental findings were compared to volume
      conductor electric field models of DBS parameterized to match the different
      experiments. Three factors directly affected the experimental and theoretical
      voltage measurements: 1) DBS electrode impedance, primarily dictated by a voltage
      drop at the electrode-electrolyte interface and the conductivity of the tissue
      medium, 2) capacitive modulation of the stimulus waveform, and 3) inhomogeneity
      and anisotropy of the tissue medium. While the voltage distribution does not
      directly predict the neural response to DBS, the results of this study do provide
      foundational building blocks for understanding the electrical parameters of DBS
      and characterizing its effects on the nervous system.

PMID- 19118552
TI  - Task-dependent compensation after pyramidal tract and dorsolateral spinal lesions
      in rats.
AB  - The purpose of this research was to investigate whether pathways in the dorsal
      part of the lateral spinal funiculus (DLF) can compensate for loss of
      corticospinal input (CST) to the spinal cord. The CST is known to control skilled
      limb movements in rats. The DLF contains several different pathways, including
      the rubrospinal tract (RST) which is also thought to influence limb movements.
      After lesions of either the corticospinal or the rubrospinal system, it is
      unclear how much of the remaining forelimb function is due to the presence of the
      alternate pathway. To begin to address this issue, the present study investigates
      the compensatory role of pathways in the DLF, including the rubrospinal tract,
      after bilateral lesions of the pyramidal tract (PT). We initially performed
      bilateral PT lesions in rats, which effectively removed the CST input to the
      spinal cord. We tested these rats during overground locomotion, skilled
      locomotion and skilled forelimb usage. After a 6 week recovery period, we then
      performed bilateral DLF lesions and compared the behavioural abilities of these
      rats to those of animals which underwent simultaneous PT and DLF lesions. If DLF
      pathways do compensate for PT lesions, then animals with PT lesions would rely
      more on DLF pathways than animals without PT lesions. Thus we hypothesized that
      animals with DLF lesions which were performed 6 weeks after PT lesions would
      exhibit more deficits on several behavioural tasks compared to animals which
      received PT and DLF lesions simultaneously. Our hypothesis was supported only for
      skilled pellet retrieval. Hence some DLF pathways, including the RST, were able
      to compensate for loss of CST input during skilled reaching but not during
      overground or skilled locomotion in PT-lesioned rats. These differential
      responses suggest that behavioural tasks vary in their reliance on specific
      pathways after injury, and, furthermore, that compensation for loss of specific
      connections can arise from numerous sources.

PMID- 19118553
TI  - Normal cortical excitability in Myoclonus-Dystonia--a TMS study.
AB  - OBJECTIVE: The aim of the present study is to investigate cortical excitability
      in patients with DYT 11 positive Myoclonus-Dystonia (M-D), using transcranial
      magnetic stimulation (TMS). METHODS: Silent period, motor evoked potential (MEP)
      recruitment curve, short interval intracortical inhibition (SICI), intracortical
      facilitation (ICF) and short interval intracortical facilitation (SICF), with
      short interstimulus intervals (ISIs) ranging from 1.2 to 3.2 ms, were studied in
      15 DYT 11-positive M-D patients and their matched controls. In four patients and
      matched controls peripheral double pulse electrical nerve stimulation was
      performed. RESULTS: All TMS parameters of cortical excitability were normal
      compared to healthy controls. In the SICF protocol we observed more variable and
      polyphasic MEPs in M-D patients. Cross-covariance analysis of MEP area revealed a
      significant correlation difference at ISI 2.2 and 2.8 ms. This increased
      variability was not seen in other TMS protocols or with peripheral nerve
      stimulation. CONCLUSIONS: In contrast with other types of dystonia, no changes in
      cortical excitability were found in DYT 11 patients. Our findings suggest that M
      D is both clinically and pathophysiologically a separate entity from other
      dystonic disorders. Polyphasic MEPs during the SICF protocol in M-D patients
      could reflect central neuron membrane instability. Application of the SICF
      protocol in other patient groups has to prove its value in movement disorders.

PMID- 19118554
TI  - B cells suppress the inflammatory response in a mouse model of primary biliary
      cirrhosis.
AB  - BACKGROUND & AIMS: Mice that express a dominant-negative form of transforming
      growth factor-beta receptor restricted to T cells (dnTGF-betaRII) develop
      antimitochondrial antibodies and liver inflammation similar to human primary
      biliary cirrhosis. METHODS: To address the role of B cells in this model of
      primary biliary cirrhosis, we bred B cell-deficient mice (Igmu(-/-)) with dnTGF
      betaRII mice, creating Igmu(-/-)dnTGF-betaRII mice, and compared the resulting
      disease phenotype with that of dnTGF-betaRII mice (controls). We also performed
      adoptive transfer of dnTGF-betaRII CD8(+) splenocytes, with or without B cells,
      to 8-week-old female Rag-1(-/-) mice to assess the role of B cells in the
      inflammatory response. RESULTS: The B cell-deficient Igmu(-/-)dnTGF-betaRII mice
      unexpectedly developed a more severe form of cholangitis than controls (dnTGF
      betaRII mice) and had a significantly greater frequency of activated CD4(+) and
      CD8(+) T cells in the liver. They also had reduced frequency of Foxp3(+)
      regulatory T cells in the hepatic CD4(+) T-cell population and natural killer
      (NK) T cells (NK1.1(+) CD3(+)) in hepatic inflammatory cell infiltrates. The
      Igmu(-/-)dnTGF-betaRII mice had increased levels of proinflammatory cytokines
      (tumor necrosis factor-alpha and interleukin-6) and developed a more severe form
      of colitis than controls. Adoptive transfer of CD8(+) splenocytes from dnTGF
      betaRII mice and peritoneal cavity-derived, but not spleen-derived, CD19(+) B
      cells into Rag-1(-/-) mice resulted in decreased amounts of liver inflammation
      and bile duct damage, compared with Rag-1(-/-) mice in which only CD8(+)
      splenocytes were transferred. CONCLUSION: B cells have a suppressive effect on
      the inflammatory response in the dnTGF-betaRII model of primary biliary
      cirrhosis.

PMID- 19118555
TI  - Mass spectrometric map of neuropeptide expression and analysis of the gamma
      prepro-tachykinin gene expression in the medaka (Oryzias latipes) brain.
AB  - Neuropeptides have important roles in modulating behavioral patterns such as
      social interaction. With the aim to determine the presence of neuropeptides known
      to be involved in social interaction as well as novel peptides, we used MALDI
      TOF/MS to analyze neuropeptide profiles in some medaka brain regions. In the
      telencephalon, hypothalamus, and pituitary gland, 3, 6, and 10 peaks,
      respectively, were identified as neuropeptides (Arg-vasotocin [AVT], growth
      hormone-releasing hormone [GHRH], neuropeptide FF, substance P [SP], somatostatin
      1 and -2, melanin-concentrating hormone [MCH], MCH gene-related peptide [Mgrp],
      melanocyte-stimulating hormone [MSH], corticotropin-like intermediate lobe
      peptide [CLIP], and beta-endorphin). The neuropeptide profile of telencephalon
      similar to that of the hypothalamus, but completely different from that of
      pituitary gland. For the future genetic analysis, we identified cDNAs encoding
      precursor proteins for the identified peptides. We also detect its expression of
      gamma-prepro-tachykinin gene encoding a SP precursor protein in both the
      telencephalon and hypothalamus. Our results indicated that the medaka brain
      contains some neuropeptides (AVT, SP, and somatostatins) that may be involved in
      modulating medaka behaviors such as social interaction.

PMID- 19118556
TI  - Allatotropin-like peptide in Malpighian tubules: insect renal tubules as an
      autonomous endocrine organ.
AB  - Malpighian tubules (MTs) are recognised as the main excretory organ in insects,
      ensuring water and mineral balance. Haematophagous insects incorporate with each
      meal a large quantity of blood, producing a particularly large volume of urine in
      a few hours. In the present study, we report the presence of an allatotropin-like
      (AT-like) peptide in MTs of Triatoma infestans (Klug). The AT-like content in MTs
      decreased during the first hours after blood-intake, correlating with the post
      prandial diuresis. In vivo artificial dilution of haemolymph showed a similar
      effect. Isolated MTs challenged with a diluted saline solution resulted in an
      autonomous and reversible response of the organ regulating the quantity of
      peptide released to the medium, and suggesting that MTs synthesise the AT-like
      peptide. While MTs are recognised as the target for several hormones, our results
      corroborate that they also have the ability to produce and secrete a hormone in
      an autonomous way.

PMID- 19118557
TI  - Romantic love modulates women's identification of men's body odors.
AB  - Romantic love is one of our most potent and powerful emotions, but very little is
      known with respect to the hormonal and psychological mechanisms in play. Romantic
      love is thought to help intimate partners stay committed to each other and two
      mechanisms have been proposed to mediate this commitment: increased attention
      towards one's partner or deflected attention away from other potential partners.
      Both mechanisms find support in the literature. We explored the potential
      influence of each of these mechanisms by assessing women's ability to identify
      (ID) body odors originating from their boyfriend, a same-sex friend, and an
      opposite-sex friend and the relationship between this ability and the degree of
      romantic love expressed towards their boyfriend. We hypothesized that an increase
      in attention towards one's partner would render a positive correlation between ID
      of a boyfriend's body odor and degree of romantic love; conversely, we
      hypothesized that attention deflected away from other potential partners would
      render a negative correlation between ID of an opposite-sex friend's body odor
      and degree of romantic love for the boyfriend. Our results supported the
      deflection theory as we found a negative correlation between the degree of
      romantic love for the subjects' boyfriends and their ability to ID the body odor
      of an opposite-sex friend but not of their boyfriend or same-sex friend. Our
      results indicate that romantic love deflects attention away from potential new
      partners rather than towards the present partner. These changes are likely
      mediated by circulating neuropeptides and a testable model is suggested.

PMID- 19118558
TI  - Neonatal hyperleptinaemia programmes anxiety-like and novelty seeking behaviours
      but not memory/learning in adult rats.
AB  - Leptin treatment during lactation programmes for leptin resistance at adulthood,
      evidenced by hyperleptinaemia, hyperphagia and overweight. Since leptin is known
      to affect stress response, emotional behaviour and memory/learning performance,
      the objective of the present study was to evaluate whether neonatal
      hyperleptinaemia programmes anxiety-like and novelty-seeking behaviours as well
      as memory/learning in adult male rats. During the first 10 days of lactation
      (from PN1 to PN10), pups were s.c. injected once per day with either 50 microL of
      saline (SAL) or murine leptin (LEP - 8 microg/100 g of body mass, saline
      diluted). Serum leptin was assessed at PN10 and at PN150. Two separate
      experiments were carried out: 1) experiment one: at PN137, 29 SAL and 30 LEP rats
      were tested in the elevated plus-maze (EPM) and, at PN142, their behaviour was
      assessed in the hole board (HB) arena; 2) experiment two: at PN140, a different
      group of rats consisting of 53 SAL and 56 LEP animals were tested in the radial
      arm water maze (RAWM). Serum leptin concentration was higher in the LEP group at
      PN10 and at PN150. LEP animals spent significantly less time in the open arms of
      the EPM. Furthermore, the number of nose-pokes in the HB arena was higher in LEP
      rats. There were no differences between groups regarding latency to find the
      hidden platform in the RAWM. Our results suggests that a central mechanism of
      leptin resistance at adulthood, caused by neonatal hyperleptinaemia, is
      associated with an increased level of anxiety and also that it intensifies
      novelty seeking-behaviour.

PMID- 19118559
TI  - A Gag peptide encompassing B- and T-cell epitopes of the caprine arthritis
      encephalitis virus functions as modular carrier peptide.
AB  - Short synthetic peptides are important tools in biomedical research permitting to
      generate hapten specific polyclonal sera for analytical purposes or functional
      studies. In this paper we provide proof of principle that a peptide located in a
      highly conserved portion of the Gag protein of the caprine arthritis encephalitis
      virus and carrying an immunodominant T helper cell epitope functions as an
      efficient carrier peptide, mediating a strong antibody response to a peptidic
      hapten encompassing a well-characterized B cell epitope of Env. The carrier and
      hapten peptides were collinearly synthesized permutating their molecular
      arrangement. While the antibody response to the hapten was similar for both
      constructs, the antibody response to a B cell epitope overlapping the T helper
      cell epitope of the Gag carrier peptide was considerably different. This permits
      a modular use of the carrier peptide to generate antibody directed exclusively to
      the hapten peptide or a strong humoral response to both carrier- and hapten
      peptide. Finally, we have mapped the epitopes involved in this polarized antibody
      response and discussed the potential immunological implications.

PMID- 19118561
TI  - Domain organization in Clostridium botulinum neurotoxin type E is unique: its
      implication in faster translocation.
AB  - Clostridium botulinum produces seven antigenically distinct neurotoxins [C.
      botulinum neurotoxins (BoNTs) A-G] sharing a significant sequence homology. Based
      on sequence and functional similarity, it was believed that their three
      dimensional structures will also be similar. Indeed, the crystal structures of
      BoNTs A and B exhibit similar fold and domain association where the translocation
      domain is flanked on either side by binding and catalytic domains. Here, we
      report the crystal structure of BoNT E holotoxin and show that the domain
      association is different and unique, although the individual domains are similar
      to those of BoNTs A and B. In BoNT E, both the binding domain and the catalytic
      domain are on the same side of the translocation domain, and all three have
      mutual interfaces. This unique association may have an effect on the rate of
      translocation, with the molecule strategically positioned in the vesicle for
      quick entry into cytosol. Botulism, the disease caused by BoNT E, sets in faster
      than any other serotype because of its speedy internalization and translocation,
      and the present structure offers a credible explanation. We propose that the
      translocation domain in other BoNTs follows a two-step process to attain
      translocation-competent conformation as in BoNT E. We also suggest that this
      translocation-competent conformation in BoNT E is a probable reason for its
      faster toxic rate compared to BoNT A. However, this needs further experimental
      elucidation.

PMID- 19118562
TI  - Interaction in vivo between the two matrix attachment regions flanking a single
      chromatin loop.
AB  - In interphase nuclei as in metaphase chromosomes, the genome is organized into
      topologically closed loop domains. Here, we have mapped the ends of the loop
      domain that contains the Ifng (interferon-gamma) gene in primary and cultured
      murine T-lymphocytes. To determine whether the ends of the loop are located in
      close proximity to each other in the nuclear space, the 3C (chromosome
      conformation capture) technique, which detects protein-mediated DNA-DNA
      interactions, was utilized. A strong interaction was demonstrated between the two
      ends of the loop, which were close enough to become cross-linked in vivo in the
      presence of paraformaldehyde. Chromatin immunoprecipitation combined with the 3C
      technique demonstrated that topoisomerase IIalpha and MeCP2, but not
      topoisomerase IIbeta, heterochromatin-associated protein HP1 or CTCF, were
      involved in this interaction. The present findings have important implications in
      terms of mechanisms of illegitimate recombination that can result in chromosomal
      translocations and deletions.

PMID- 19118560
TI  - Cardioprotective signaling to mitochondria.
AB  - Mitochondria are central players in the pathophysiology of ischemia-reperfusion.
      Activation of plasma membrane G-coupled receptors or the Na,K-ATPase triggers
      cytosolic signaling pathways that result in cardioprotection. Our working
      hypothesis is that the occupied receptors migrate to caveolae, where signaling
      enzymes are scaffolded into signalosomes that bud off the plasma membrane and
      migrate to mitochondria. The signalosome-mitochondria interaction then initiates
      intramitochondrial signaling by opening the mitochondrial ATP-sensitive K(+)
      channel (mitoK(ATP)). MitoK(ATP) opening causes an increase in ROS production,
      which activates mitochondrial protein kinase C epsilon (PKCvarepsilon), which
      inhibits the mitochondrial permeability transition (MPT), thus decreasing cell
      death. We review the experimental findings that bear on these hypotheses and
      other modes of protection involving mitochondria.

PMID- 19118563
TI  - Transcriptional regulation of the human prostacyclin receptor gene is dependent
      on Sp1, PU.1 and Oct-1 in megakaryocytes and endothelial cells.
AB  - Prostacyclin plays a central role in hemostasis, inflammation and nociception.
      However, the factors regulating expression of the prostacyclin receptor (IP) gene
      in humans and in other species have not been identified. In this study, we sought
      to identify the key trans-acting factors and cis-acting elements regulating IP
      expression in the megakaryoblastic human erythroleukemia (HEL) 92.1.7 and
      vascular endothelial EA.hy 926 cell lines. With the use of deletion and genetic
      reporter analyses, the essential core promoter, termed PrmIP, was localized to
      the -1022 to -895 region proximal to the transcription initiation site, while an
      upstream repressor region, localized to -1502 to -1271, was also identified.
      Bioinformatic analysis revealed evolutionarily conserved Sp1, PU.1 and Oct-1
      sites within the core PrmIP, and disruption of these elements each led to
      substantial reductions in PrmIP-directed gene expression in both HEL and EA.hy
      926 cells. Electrophoretic mobility shift and supershift assays established that
      Sp1, PU.1 and Oct-1 can bind to elements within the core promoter in vitro, while
      chromatin immunoprecipitation assays confirmed their specific binding to
      chromatin in vivo. Furthermore, combination mutations of the Sp1, PU.1 and Oct-1
      elements revealed that they act independently to co-regulate basal transcription
      of the IP gene, while ectopic expression of each of the trans-acting factors led
      to substantial increases in PrmIP-directed gene expression and IP mRNA expression
      in both HEL and EA.hy 926 cells. While electrophoretic mobility shift and
      antibody supershift assays established that the Ets family member Fli1, but not
      Ets-1, is capable of binding to the PU.1 element within PrmIP in vitro, chromatin
      immunoprecipitation analysis established that neither Fli1 nor Ets-1 binds to
      that element in vivo. Collectively, these data provide critical insights into the
      transcriptional regulation of the IP gene in human megakaryocytic and endothelial
      cells, identifying Sp1, PU.1 and Oct-1 as the critical factors involved in its
      basal regulation in humans.

PMID- 19118564
TI  - Angiogenesis, hypoxia and VEGF expression during tumour growth in a human
      xenograft tumour model.
AB  - Tumour growth and spread of tumour cells requires angiogenesis. Incipient
      angiogenesis is not induced by tumour cell hypoxia but probably by proangiogenic
      factors. During growth tumours depend on a further induction of vascular
      development for adequate oxygen and nutrient supply. If the oxygen supply is
      insufficient, the resulting hypoxia stimulates angiogenesis through upregulation
      of HIF-1 alpha and VEGF. VEGF upregulation is associated with a poor response to
      treatment and poor prognosis. The aim of the study was to analyze the
      interrelationship between hypoxia and angiogenesis during tumour growth.
      Therefore the tumour vasculature architecture and functional properties of the
      vessels were studied during subsequent phases of tumour growth in relation to
      hypoxia and VEGF-expression. Tumours from the human glioblastoma multiforme
      tumour line E106 were transplanted in athymic mice. Tumours were harvested at 2
      days after transplantation and when tumours reached a mean size of 2, 4, 6, 8 and
      10 mm. VEGF was present early in the onset of angiogenesis independent of HIF-1
      alpha. During tumour growth VEGF increased from 0.94 to 7.27 ng/mg assessed by
      ELISA. However, there was increasing intratumoural heterogeneity in the
      architecture of the tumours, even in the largest tumours small well oxygenated
      areas were detected resembling the relatively well organized architecture of the
      smallest tumours. The observation that tumour vasculature develops in early
      phases under normoxic and at later phases under hypoxic conditions with the
      presence of both conditions in the larger tumours, suggested that anti-angiogenic
      therapy should be directed towards HIF-1 alpha dependent and HIF 1-alpha
      independent pathways.

PMID- 19118565
TI  - Another look at the Muller-Lyer illusion: different gaze patterns in vision for
      action and perception.
AB  - Following Goodale and Milner's [Goodale, M. A., & Milner, A. D. (1992). Separate
      visual pathways for perception and action. Trends in Neurosciences, 15(1), 20-25]
      proposal to distinguish the dorsal and ventral systems on basis of the functional
      demands they serve (i.e., action and perception), a vast literature has emerged
      that scrutinized if the dorsal and ventral systems indeed process information
      into egocentric and allocentric codes in accordance with their respective
      functions. However, a corollary of Goodale and Milner's original proposal, that
      these functional demands also impose different constraints on information
      detection, has been largely overlooked. In the present study, we measured gaze
      patterns to investigate how information detection for action and perception
      differs. In two conditions, participants (N=9) grasped or made a manual estimate
      of the length of a shaft embedded in a Muller-Lyer configuration. The illusion
      significantly affected the manual estimates, but not the hand aperture during
      grasping. In line with these behavioral findings, significant differences in gaze
      patterns were revealed between the two tasks. Participants spent more time
      looking at areas that contain egocentric information (i.e., centre of the shaft)
      when grasping as compared to making a manual length estimate. In addition,
      participants, made more gaze shifts (i.e., especially between the two areas
      surrounding the shaft endpoints and including the arrowheads) when making the
      manual length estimate, enabling the pick up of allocentric information. This
      difference was more pronounced during task execution as compared to task
      preparation (i.e., before movement onset). These results support the contention
      that the functional distinction between the dorsal and ventral systems is not
      limited to the processing of information, but also encompasses the detection of
      information.

PMID- 19118566
TI  - Integrated actions of progesterone receptor and cell cycle machinery regulate
      breast cancer cell proliferation.
AB  - Multiple laboratories have investigated progesterone receptor (PR) involvement in
      breast cancer cell cycle progression. There is now a growing body of evidence
      demonstrating complex interactions between PR and cell cycle regulatory proteins.
      Here we review the current literature linking PR to cell cycle control and
      discuss gaps in the current knowledge. A more complete understanding of the
      relationships between PR and cell cycle regulatory molecules may reveal
      additional avenues for prevention and treatment of steroid receptor positive
      breast cancers.

PMID- 19118567
TI  - Use of mRNA expression to detect the induction of drug metabolising enzymes in
      rat and human hepatocytes.
AB  - It is important to investigate the induction of cytochrome P450 (CYP) enzymes by
      drugs. The most relevant end point is enzyme activity; however, this requires
      many cells and is low throughput. We have compared the CYP1A, CYP2B and CYP3A
      induction response to eight inducers in rat and human hepatocytes using enzyme
      activities (CYP1A2 (ethoxyresorufin), 2B (benzoxyresorufin for rat and bupropion
      for human) and CYP3A (testosterone)) and Taqman Low Density Array (TLDA)
      analysis. There was a good correlation between the induction of CYP1A2, CYP2B6
      and CYP3A4 enzyme activities and mRNA expression in human hepatocytes. In
      contrast, BROD activities and mRNA expression in rat hepatocytes correlated
      poorly. However, bupropion hydroxylation correlated well with Cyp2b1 expression
      in rat hepatocytes. TLDA analysis of a panel of mRNAs encoding for CYPs, phase 2
      enzymes, nuclear receptors and transporters revealed that the main genes induced
      by the 8 compounds tested were the CYPs. AhR ligands also induced UDP
      glucuronosyltransferases and glutathione S-transferases in rat and human
      hepatocytes. The transporters, MDR1, MDR3 and OATPA were the only transporter
      genes significantly up-regulated in human hepatocytes. In rat hepatocytes Bsep,
      Mdr2, Mrp2, Mrp3 and Oatp2 were up-regulated. We could then show a good in
      vivo:in vitro correlation in the induction response of isolated rat hepatocytes
      and ex-vivo hepatic microsomes for the drug development candidate, EMD392949. In
      conclusion, application of TLDA methodology to investigate the potential of
      compounds to induce enzymes in rat and human hepatocytes increases the throughput
      and information gained from one assay, without reducing the predictive capacity.

PMID- 19118568
TI  - Toxicokinetics of acrylamide in rats and humans following single oral
      administration of low doses.
AB  - The rodent carcinogen acrylamide (AA) is formed during preparation of starch
      containing foods. AA is partly metabolized to the genotoxic epoxide glycidamide
      (GA). After metabolic processing, the mercapturic acids N-acetyl-S-(2
      carbamoylethyl)-L-cysteine (AAMA), rac-N-acetyl-S-(2-carbamoyl-2-hydroxyethyl)-L
      cysteine (GAMA) and rac-N-acetyl-S-(1-carbamoyl-moyl-2-hydroxyethyl)-L-cysteine
      (iso-GAMA) are excreted with urine. In humans, AAMA can be sulfoxidized to AAMA
      sulfoxide. The aim of this study was to assess potential species-differences in
      AA-toxicokinetics in rats and humans after single oral administration of doses
      similar to the daily human dietary exposure. Male Fischer 344 rats (n=5/dose
      group) were administered 20 and 100 microg/kg b.w. (13)C(3)-AA in deionized water
      via oral gavage. Human subjects (n=3/gender) were orally administered 0.5 and 20
      microg/kg b.w. (13)C(3)-AA with drinking water. Urine samples were collected in
      intervals for 96 and 94 h, respectively. Urinary concentrations of (13)C(3)-AAMA,
      (13)C(3)-GAMA and (13)C(3)-AAMA-sulfoxide were monitored by liquid chromatography
      tandem mass spectrometry. The recovered urinary metabolites accounted for 66.3%
      and 70.5% of the 20 and 100 microg/kg b.w. doses in rats and for 71.3% and 70.0%
      of the 0.5 and 20 microg/kg b.w. doses in humans. In rats, (13)C(3)-AAMA
      accounted for 33.6% and 38.8% of dose and 32.7% and 31.7% of dose was recovered
      as (13)C(3)-GAMA; (13)C(3)-AAMA-sulfoxide was not detected in rat urine. In
      humans, (13)C(3)-AAMA, (13)C(3)-GAMA and (13)C(3)-AAMA-sulfoxide accounted for
      51.7% and 49.2%, 6.3% and 6.4% and 13.2% and 14.5% of the applied dose,
      respectively. The obtained results suggest that the extent of AA bioactivation to
      GA in humans is lower than in rodents.

PMID- 19118569
TI  - Induction of hsp70, hsp60, hsp83 and hsp26 and oxidative stress markers in
      benzene, toluene and xylene exposed Drosophila melanogaster: role of ROS
      generation.
AB  - Exposure to benzene, toluene and xylene in the human population may pose a health
      risk. We tested a working hypothesis that these test chemicals cause cellular
      toxicity to a non-target organism, Drosophila melanogaster. Third instar larvae
      of D. melanogaster transgenic for hsp70, hsp83 and hsp26 and Oregon R(+) strain
      were exposed to 1.0-100.0 mM benzene, toluene and xylene for 2-48 h to examine
      the heat shock proteins (hsps), ROS generation, anti-oxidant stress markers and
      developmental end points. The test chemicals elicited a concentration- and time
      dependent significant (p<0.01) induction of the hsps in the exposed organism in
      the order of hsp70>hsp83>or=hsp26 as evident by beta-galactosidase activity after
      24 h. RT-PCR amplification studies in Oregon R(+) larvae revealed a similar
      induction pattern of these genes along with hsp60 in the order of
      hsp70>hsp60>hsp26>or=hsp83. Under similar experimental conditions, a significant
      induction of ROS generation and oxidative stress markers viz. superoxide
      dismutase, catalase, glutathione S-transferase, thioredoxin reductase,
      glutathione, malondialdehyde and protein carbonyl content was observed. Sub
      organismal response was propagated towards organismal response i.e., a delay in
      the emergence of flies and their reproductive performance. While hsp70 was
      predominantly induced in the organism till 24 h of treatment with the test
      chemicals, a significant or insignificant regression of Hsp70 after 48 h was
      concurrent with a significant induction (p<0.01) of hsp60>hsp83>or=hsp26 in
      comparison to the former. A significant positive correlation was observed between
      ROS generation and these hsps in the exposed organism till 24 h and a negative
      correlation between ROS generation and hsp70 in them after 48 h indicating a
      modulatory role of ROS in the induction of hsps. The study suggests that among
      the tested hsps, hsp70 may be used as an early bioindicator of cellular toxicity
      against benzene, toluene and xylene and D. melanogaster as an alternative animal
      model for screening the risk posed by environmental chemicals.

PMID- 19118570
TI  - Race and the validity of self-reported cancer screening behaviors: development of
      a conceptual model.
AB  - BACKGROUND: Many estimates of cancer screening are based on self-reported
      screening behavior. There is growing concern that self-reported screening
      measures may be less accurate among members of racial and ethnic minority groups.
      This would have considerable implications for research on racial and ethnic
      disparities in cancer screening. OBJECTIVES: To review the literature on the
      relationship between race/ethnicity and the accuracy of self-reported cancer
      screening behavior and develop a conceptual framework that would provide a deeper
      understanding of factors underlying this relationship. METHODS: We developed a
      conceptual framework drawing from diverse literatures including validation
      studies examining the accuracy of self-reported cancer screening behaviors and
      articles on survey response bias. RESULTS AND CONCLUSIONS: Evidence suggests that
      racial and ethnic minorities may be less likely to provide accurate reports of
      their cancer screening behavior and that overreporting may be particularly
      problematic. Research conducted in other areas suggests that these sources of
      measurement error may stem from cognitive and motivational processes and that
      they can be moderated by question wording and data collection characteristics. At
      this point, however, the quality of the evidence is not strong and more research
      is needed before definitive conclusions can be drawn.

PMID- 19118571
TI  - Co-application of arsenic trioxide (As2O3) and cisplatin (CDDP) on human SY-5Y
      neuroblastoma cells has differential effects on the intracellular calcium
      concentration ([Ca2+]i) and cytotoxicity.
AB  - Arsenic trioxide (As(2)O(3)) and cisplatin (CDDP) are clinically relevant
      chemotherapeutics which modulate the intracellular calcium concentration
      ([Ca(2+)](i)) by different mechanisms: As(2)O(3) depletes intracellular calcium
      stores while CDDP triggers an influx of Ca(2+). We investigate whether co
      application of As(2)O(3) and CDDP has an effect on [Ca(2+)](i) homeostasis,
      resulting in an increase of cytotoxicity/apoptosis in human SY-5Y neuroblastoma
      cells. Confocal imaging with Ca(2+)-sensitive dye (fluo-4) was used for
      investigating [Ca(2+)](i) dynamics. The induction of cell death was assayed using
      Trypan blue exclusion and Hoechst 33347 staining. Application of As(2)O(3)
      (1microM) or CDDP (1microM) increased [Ca(2+)](i). The largest elevation was
      observed when the basic [Ca(2+)](i) concentration was low. Both, transient and
      sustained [Ca(2+)](i)-increases were observed in response to a single application
      of As(2)O(3) or CDDP. Sustained increase showed clear additive effects when both
      drugs were co-applied. The magnitude of the [Ca(2+)](i)-increase depends on the
      order of application; the most pronounced effect occurred when the cells were
      preincubated with CDDP followed by a co-application with As(2)O(3). The sustained
      [Ca(2+)](i) elevations resulted in increased cytotoxicity and apoptosis.
      Therefore, co-treatment with CDDP and As(2)O(3) may be a more effective anti
      cancer therapy then either agent alone.

PMID- 19118572
TI  - The R6 lines of transgenic mice: a model for screening new therapies for
      Huntington's disease.
AB  - Huntington's disease (HD) is a hereditary neurodegenerative disorder caused by an
      expanded CAG repeat in the HD gene that results in cortical and striatal
      degeneration, and mutant huntingtin aggregation. Current treatments are
      unsatisfactory. R6 transgenic mice replicate many features of the human
      condition, show early onset of symptoms and fast disease progression, being one
      of the most used models for therapy screening. Here we review the therapies that
      have been tested in these mice: environmental enrichment, inhibition of histone
      deacetylation and methylation, inhibition of misfolding and oligomerization,
      transglutaminase inhibition, rescue of metabolic impairment, amelioration of the
      diabetic phenotype, use of antioxidants, inhibition of excitotoxicity, caspase
      inhibition, transplantation, genetic manipulations, and restoration of
      neurogenesis. Although many of these treatments were beneficial in R6 mice, they
      may not be as effective in HD patients, and thus the search for a combination of
      therapies that will rescue the human condition continues.

PMID- 19118573
TI  - Effective electromagnetic noise cancellation with beamformers and synthetic
      gradiometry in shielded and partly shielded environments.
AB  - The major challenge of MEG, the inverse problem, is to estimate the very weak
      primary neuronal currents from the measurements of extracranial magnetic fields.
      The non-uniqueness of this inverse solution is compounded by the fact that MEG
      signals contain large environmental and physiological noise that further
      complicates the problem. In this paper, we evaluate the effectiveness of magnetic
      noise cancellation by synthetic gradiometers and the beamformer analysis method
      of synthetic aperture magnetometry (SAM) for source localisation in the presence
      of large stimulus-generated noise. We demonstrate that activation of primary
      somatosensory cortex can be accurately identified using SAM despite the presence
      of significant stimulus-related magnetic interference. This interference was
      generated by a contact heat evoked potential stimulator (CHEPS), recently
      developed for thermal pain research, but which to date has not been used in a MEG
      environment. We also show that in a reduced shielding environment the use of
      higher order synthetic gradiometry is sufficient to obtain signal-to-noise ratios
      (SNRs) that allow for accurate localisation of cortical sensory function.

PMID- 19118575
TI  - Test-retest reliability of motor evoked potentials (MEPs) at the submental muscle
      group during volitional swallowing.
AB  - Motor evoked potentials (MEPs) recorded from pharyngeal and anterior hyo
      mandibular (submental) muscles at rest have been used to evaluate treatment
      effects on neural pathways underlying swallowing. This study documents a novel
      methodological approach of recording reliable intra- and inter-session MEPs at
      the submental muscle group during task-related volitional swallowing. MEPs were
      elicited by single-pulse transcranial magnetic stimulation (TMS), triggered by a
      custom-made system when a pre-set level of surface electromyographic activity in
      the target muscles was breached. Fifteen MEPs were recorded during each of four
      sessions. Intraclass correlation coefficients (ICCs) were used to assess test
      retest reliability within and across sessions for blocks of 3, 5, 10 and 15
      trials. Highly reliable intra-session reliability was achieved, maximal for
      blocks of five trials (0.915). Inter-session reliability varied between 0.474
      (three trials per block) and 0.909 (10 trials per block). Surface
      electromyography-triggered TMS allows reliable measurement of MEP amplitude at
      the submental muscle group within and across sessions when muscles are pre
      activated during volitional swallowing. This methodology will be useful for
      future investigations on the effects of pathology and modulation of swallowing
      neural pathways.

PMID- 19118574
TI  - Effects of ciliary neurotrophic factor and leukemia inhibiting factor on oxytocin
      and vasopressin magnocellular neuron survival in rat and mouse hypothalamic
      organotypic cultures.
AB  - Organotypic cultures of mouse and rat magnocellular neurons (MCNs) in the
      hypothalamo-neurohypophysial system (HNS) have served as important experimental
      models for the molecular and physiological study of this neuronal phenotype.
      However, it has been difficult to maintain significant numbers of the MCNs,
      particularly vasopressin MCNs, in these cultures for long periods. In this paper,
      we describe the use of the neurotrophic factors, leukemia inhibiting factor (LIF)
      and ciliary neurotrophic factor (CNTF) to rescue rat vasopressin (Avp)- and
      oxytocin (Oxt)-MCNs from axotomy-induced, programmed cell death in vitro.
      Quantitative data are presented for the efficacy of the LIF family of
      neurotrophic factors on the survival of MCNs in three nuclei, the paraventricular
      (PVN), supraoptic (SON), and accessory (ACC) nuclei in the mouse and rat
      hypothalamus.

PMID- 19118576
TI  - Premature senescence of T lymphocytes from patients with beta-thalassemia major.
AB  - Several researches have demonstrated a suppressed cell mediated immunity in
      patients with beta-thalassemia major. To know whether the premature aging of T
      cells is involved in abnormalities of cell mediated immunity, the biomarkers of
      immunosenescence including telomerase activity, apoptosis, and the expression of
      CD28 and CD95 were evaluated in T lymphocytes from beta-thalassemia major
      patients. The ex vivo spontaneous apoptosis in CD4(+) or CD8(+) T cells from
      patients and healthy subjects was assessed by an in situ TdT mediated dUTP-biotin
      nick end labelling (TUNEL) assay after 24h incubation in medium. Flow cytometric
      data revealed that lymphocytes from beta-thalassemia patients were resistant to
      spontaneous apoptosis compared to the normal lymphocytes. Moreover, the
      percentages of TUNEL(+)CD4(+) or TUNEL(+)CD8(+) T cells from patients were
      significantly lower than those control cells. Quantitative determination of
      telomerase activity in resting and activated T cells was performed using the
      Telomeric Repeat Amplification Protocol (TRAP). The results showed a decreased
      telomerase activity of activated T cells in patients with thalassemia major
      compared to that in healthy controls. However, the percentages of CD8(+)CD28(-)
      and CD3(+)CD95(+) T lymphocytes were significantly higher in thalassemia
      patients, indicating the phenotypes associated with senescent T lymphocytes.
      These data provide evidences for the occurrence of accelerated aging of T cells
      in beta-thalassemia major; possibly result in abnormal T cell function leading to
      suppressed cell mediated immunity.

PMID- 19118577
TI  - Effective suppression of replication of porcine reproductive and respiratory
      syndrome virus by adenovirus-mediated small interfering RNAs targeting ORF1b, 5
      and 7 genes.
AB  - Porcine reproductive and respiratory syndrome virus has caused hundreds of
      thousands of deaths in pig farms in many swine-producing areas in the world in
      recent years. However, at present there is no effective method to prevent and
      control the disease, and there is a need to develop new antiviral strategies. In
      this study, four recombinant adenoviruses expressing shRNAs targeting ORF1b, ORF5
      and ORF7 were constructed, and it was found that they could down-regulate
      effectively specific gene expression and inhibit viral replication in MARC-145
      cells when compared to the controls. They could also inhibit effectively PRRSV
      replication in porcine alveolar macrophages. The inhibition effect was dose
      dependent and could be sustained for at least 96h in macrophages. In addition,
      PRRSV replication could be suppressed significantly by shRNA in cells infected
      previously or simultaneously with PRRSV. The results indicated that the shRNA
      expressing rAd5 targeting to various gene regions of PRRSV might be a potential
      anti-PRRSV strategy.

PMID- 19118578
TI  - Advantages of COS-1 monkey kidney epithelial cells as packaging host for small
      volume production of high-quality recombinant lentiviruses.
AB  - The HEK293T human embryonic kidney cells have been used widely as a packaging
      host for transfection-based production of recombinant lentiviruses. The present
      study describes advantages of using COS-1 African green monkey kidney cells
      versus HEK293T cells as a packaging host for small-volume production of high
      quality recombinant lentiviruses. The particle performance index, defined as the
      ratio of infection-competent viral particles to the total number of particles,
      was three- to four-fold greater in transfection supernatants generated using COS
      1 cells than that generated using HEK293T cells. Adhesion of HEK293T cells to the
      cell culture-treated plastic surface was weak, causing significant HEK293T cell
      contamination in the transfection supernatants produced by laboratory automation
      using the 96-well cell culture plates. In contrast, COS-1 cells adhered strongly
      to the plastic surface, and cell contamination was not detected in the
      transfection supernatants. These results suggest that COS-1 cells may be a useful
      alternative packaging host for use for automated generation of large numbers of
      high-quality lentivirus reagents, particularly because they eliminate the need
      for additional purification steps to remove viral particles from cell culture
      supernatant.

PMID- 19118579
TI  - High-throughput screening using pseudotyped lentiviral particles: a strategy for
      the identification of HIV-1 inhibitors in a cell-based assay.
AB  - Two decades after its discovery the human immunodeficiency virus (HIV) is still
      spreading worldwide and killing millions. There are 25 drugs formally approved
      for HIV currently on the market, but side effects as well as the emergence of HIV
      strains showing single or multiple resistances to current drug-therapy are causes
      for concern. Furthermore, these drugs target only 4 steps of the viral cycle,
      hence the urgent need for new drugs and also new targets. In order to tackle this
      problem, we have devised a cell-based assay using lentiviral particles to look
      for post-entry inhibitors of HIV-1. We report here the assay development,
      validation as well as confirmation of the hits using both wild-type and drug
      resistant HIV-1 viruses. The screening was performed on an original library, rich
      in natural compounds and pure molecules from Traditional Chinese Medicine
      pharmacopoeia, which had never been screened for anti-HIV activity. The
      identified hits belong to four chemical sub-families that appear to be all non
      nucleoside reverse transcriptase inhibitors (NNRTIs). Secondary tests with live
      viruses showed that there was good agreement with pseudotyped particles,
      confirming the validity of this approach for high-throughput drug screens. This
      assay will be a useful tool that can be easily adapted to screen for inhibitors
      of viral entry.

PMID- 19118580
TI  - Parcellation of parietal cortex: convergence between lesion-symptom mapping and
      mapping of the intact functioning brain.
AB  - Spatial-attentional deficits are highly prevalent following stroke. They can be
      clinically detected by means of conventional bedside tests such as target
      cancellation, line bisection and the visual extinction test. Until recently,
      lesion mapping studies and functional imaging of the intact brain did not agree
      very well on exactly which parietal areas play a key role in selective attention:
      the inferior parietal lobule or the intraparietal sulcus. Recently, the use of a
      contrastive approach in patients akin to that commonly used in functional imaging
      studies in healthy volunteers together with voxel-based lesion-symptom mapping
      have allowed to bring the patient lesion mapping much closer to the functional
      imaging results obtained in healthy controls. In this review we focus on
      converging evidence obtained from patient lesion studies and from fMRI studies in
      the intact brain in humans. This has yielded novel insights into the functional
      segregation between the middle third of the intraparietal sulcus, the superior
      parietal lobule and the temporoparietal junction in the intact brain and also
      enhanced our understanding of the pathogenetic mechanisms underlying deficits
      arising in patients.

PMID- 19118583
TI  - Role of intracellular calcium and S-glutathionylation in cell death induced by a
      mixture of isothiazolinones in HL60 cells.
AB  - Previously we reported that brief exposure of HL60 cells to a mixture of 5-chloro
      2-methyl-4-isothiazolin-3-one (CMI) and 2-methyl-4-isothiazolin-3-one (MI) shifts
      the cells into a state of oxidative stress that induces apoptosis and necrosis.
      In this study, flow cytometric analysis showed that CMI/MI induces early
      perturbation of calcium homeostasis, increasing cytosolic and mitochondrial
      calcium and depleting the intracellular endoplasmic reticulum (ER) stores. The
      calcium chelator BAPTA-AM reduced necrosis and secondary necrosis, the loss of
      DeltaPsim and S-glutathionylation induced by necrotic doses of CMI/MI, but did
      not protect against CMI/MI-induced apoptosis, mitochondrial calcium uptake and
      mitochondrial hyperpolarization. This indicates that increased cytoplasmic
      calcium does not have a causal role in the induction of apoptosis, while cross
      talk between the ER and mitochondria could be responsible for the induction of
      apoptosis. GSH-OEt pretreatment, which enhances cellular GSH content, reduced S
      glutathionylation and cytosolic and mitochondrial calcium levels, thus protecting
      against both apoptosis and necrosis shifting to apoptosis. Therefore, the degree
      of GSH depletion, paralleled by the levels of protein S-glutathionylation, may
      have a causal role in increasing calcium levels. The mitochondrial calcium
      increase could be responsible for apoptosis, while necrosis is associated with
      cytoplasmic calcium overload. These findings suggest that S-glutathionylation of
      specific proteins acts as a molecular linker between calcium and redox
      signalling.

PMID- 19118582
TI  - A novel mode of translocation for cytolethal distending toxin.
AB  - Thermal instability in the toxin catalytic subunit may be a common property of
      toxins that exit the endoplasmic reticulum (ER) by exploiting the mechanism of ER
      associated degradation (ERAD). The Haemophilus ducreyi cytolethal distending
      toxin (HdCDT) does not utilize ERAD to exit the ER, so we predicted the
      structural properties of its catalytic subunit (HdCdtB) would differ from other
      ER-translocating toxins. Here, we document the heat-stable properties of HdCdtB
      which distinguish it from other ER-translocating toxins. Cell-based assays
      further suggested that HdCdtB does not unfold before exiting the ER and that it
      may move directly from the ER lumen to the nucleoplasm. These observations
      suggest a novel mode of ER exit for HdCdtB.

PMID- 19118584
TI  - Relative effects of demand and control on task-related cardiovascular reactivity,
      task perceptions, performance accuracy, and mood.
AB  - The hypothesis that work control has beneficial effects on well-being is the
      basis of the widely applied, yet inconsistently supported, Job Demand Control
      (JDC) Model [Karasek, R.A., 1979. Job demands, job decision latitude and mental
      strain: Implications for job redesign. Adm. Sci. Q. 24, 285-308.; Karasek, R.,
      Theorell, T., 1990. Healthy Work: Stress, Productivity, and the Reconstruction of
      Working Life. Basic Books, Oxford]. The model was tested in an experiment (N=60)
      using a cognitive stressor paradigm that sought to prevent confounding between
      demand and control. High-demand was found to be associated with deleterious
      effects on physiological, subjective, and performance outcomes. In contrast, few
      main effects were found for control. Evidence for the buffer interpretation of
      the JDC Model was limited to a significant demand-control interaction for
      performance accuracy, whereas substantial support was found for the strain
      interpretation of the model [van der Doef, M., Maes, S., 1998. The job demand
      control(-support) model and physical health outcomes: A review of the strain and
      buffer hypotheses. Psychol. Health 13, 909-936., van der Doef, M., Maes, S.,
      1999. The Job Demand-Control(-Support) model and psychological well-being: A
      review of 20 years of empirical research. Work Stress 13, 87-114]. Manipulation
      checks revealed that objective control altered perceptions of control but not
      perceptions of demand. It is suggested that beneficial effects of work-related
      control are unlikely to occur in the absence of reductions in perceived demand.
      Thus, contrary to the propositions of Karasek and colleagues, demand and control
      do not appear to be independent factors.

PMID- 19118585
TI  - Adult neurogenesis and its alteration under pathological conditions.
AB  - Even in the adult brain, neural stem cells in the dentate gyrus and
      subventricular zone continue to produce neuronal precursors, which migrate and
      differentiate into functional mature neurons. This physiological neurogenesis is
      thought to be involved in neuronal plasticity. Moreover, recent studies indicate
      that adult neurogenesis can change in response to various brain insults,
      including psychiatric diseases, stroke, and neurodegenerative disorders. Although
      increased neurogenesis in these pathological conditions could contribute to the
      restoration and regeneration of the damaged brain, an inadequate and/or excessive
      supply of new neurons, or suppressed neurogenesis, could contribute to their
      pathophysiology. To develop successful regenerative treatments for the injured
      brain, we need to understand more precisely and comprehensively the mechanisms
      regulating adult neurogenesis under both physiological and pathological
      conditions.

PMID- 19118586
TI  - Southern tomato virus: The link between the families Totiviridae and
      Partitiviridae.
AB  - A dsRNA virus with a genome of 3.5 kb was isolated from field and greenhouse
      grown tomato plants of different cultivars and geographic locations in North
      America. Cloning and sequencing of the viral genome showed the presence of two
      partially overlapping open reading frames (ORFs), and a genomic organization
      resembling members of the family Totiviridae that comprises fungal and protozoan
      viruses, but not plant viruses. The 5'-proximal ORF codes for a 377 amino acid
      long protein of unknown function, whereas the product of ORF2 contains typical
      motifs of an RNA-dependant RNA-polymerase and is likely expressed by a +1
      ribosomal frame shift. Despite the similarity in the genome organization with
      members of the family Totiviridae, this virus shared very limited sequence
      homology with known totiviruses or with other viruses. Repeated attempts to
      detect the presence of an endophytic fungus as the possible host of the virus
      failed, supporting its phytoviral nature. The virus was efficiently transmitted
      by seed but not mechanically and/or by grafting. Phylogenetic analyses revealed
      that this virus, for which the name Southern tomato virus (STV) is proposed,
      belongs to a partitivirus-like lineage and represents a species of a new taxon of
      plant viruses.

PMID- 19118587
TI  - The A312L 5'-UTR of Chlorella virus PBCV-1 is a translational enhancer in
      Arabidopsis thaliana.
AB  - PBCV-1 (Paramecium bursaria Chlorella virus) is a large double stranded DNA virus
      that replicates in certain eukaryotic chlorella like green algae. The PBCV-1
      A312L gene encodes a 33-kDa protein whose function currently is unknown. The 5'
      UTR of the A312L mRNA is 153 nucleotides, longer than the 5'-UTR in any other
      PBCV-1 gene. The sequence 5'-AAAC was repeated 17 times within 156bp 5' to the
      A312L gene start codon and this sequence was repeated 13 times continuously in
      the 5'-UTR of the mRNA. Recombinant genes were constructed in vector pBI121 that
      contained the A312L 5'-UTR, in both the forward and inverse-complement
      orientations, fused to the GUS gene under the control of the CaMV 35S promoter.
      These constructs were introduced into Arabidopsis thaliana and the results
      indicated that the A312L 5'-UTR functions as a translational enhancer only in the
      forward orientation. Overall, the ratio of GUS enzyme activity to GUS mRNA was 15
      fold higher in constructs derived from the A312L 5'-UTR in the forward
      orientation as compared to constructs containing the 5'-UTR in the inverse
      complement orientation or those lacking the A312L 5'-UTR.

PMID- 19118581
TI  - Generation and analysis of expressed sequence tags from a cDNA library of
      Moniezia expansa.
AB  - The Moniezia expansa is a parasite of sheep that causes diarrhea and fleshless
      leading to stockbreeding losses. A genomic resource for large-scale molecular
      studies in this parasite is lacking. To study the gene expression including
      development, digestion and reproduction organs of M. expansa, a cDNA library had
      been constructed and expressed sequence tags (ESTs) had been analyzed, which were
      helpful for the development of a powerful microarray platform which are used to
      analyze gene expression in this species. cDNAs are useful resources in annotating
      genes and providing functional analysis of genes. In this study, a cDNA library
      from adult cestode of M. expansa was created and 2642 ESTs from 5'-ends of the
      cDNA clones representing 1081 unigenes were obtained. Cluster analysis of these
      ESTs allowed identification of 1081 unique sequences containing 351 contigs and
      730 singletons. BLASTX searches identified 780 significant (E-value<10(-5)) hits
      and further Gene Ontology (GO) analysis was used to annotate these genes. All the
      EST sequences were deposited under dbEST in GenBank (GenBank: FE905224-FE905315,
      FE942104-FE942773, FE969189-FE969190, FF677548-FF677734, FF848124-FF848253).
      Although we only obtained 1081 unigenes, the set of ESTs identified represents a
      significant proportion of the M. expansa and provides molecular resource for the
      development of microarrays for gene expression studies concerning development,
      metabolism and reproduction.

PMID- 19118588
TI  - A novel mycovirus associated with four double-stranded RNAs affects host fungal
      growth in Alternaria alternata.
AB  - Four double-stranded RNAs (dsRNAs), referred to as dsRNA 1 (3617 bp), dsRNA 2
      (2794 bp), dsRNA 3 (2576 bp) and dsRNA 4 (1420 bp), were detected in the EGS 35
      193 strain of Alternaria alternata at high concentration ( approximately 3
      microg/g dried mycelium). This strain had an impaired growth phenotype. By
      exposing the strain to cycloheximide during hyphal tip isolation, we isolated
      strains which had normal mycelial growth and pigmentation, in which decreased
      levels of the dsRNAs were observed ( approximately 0.3 microg/g dried mycelium).
      These results indicate that this dsRNA mycovirus might be involved in modulating
      traits of its fungal host, A. alternata. The buoyant density of isometric virus
      particles (about 33 nm in diameter) containing these dsRNAs in CsCl was 1.35-1.40
      g/cm(3) depending on the size of the packaged dsRNAs. The dsRNA 1 encodes a
      single open reading frame (3447 nt) containing the conserved motifs of viral RNA
      dependent RNA polymerase (RdRp), which is related to the ORF encoded by dsRNA 1
      of Aspergillus mycovirus 341. It is noteworthy that all of the coding strands of
      the four dsRNA genomes have 3'-poly (A) tails ranging from 33 to 50 nt in length.
      We named this novel dsRNA mycovirus in the EGS 35-193 strain A. alternata virus-1
      (AaV-1).

PMID- 19118589
TI  - Physiological and pharmacological roles of ABCG2 (BCRP): recent findings in Abcg2
      knockout mice.
AB  - The multidrug transporter ABCG2 (BCRP/MXR/ABCP) can actively extrude a broad
      range of endogenous and exogenous substrates across biological membranes. ABCG2
      limits oral availability and mediates hepatobiliary and renal excretion of its
      substrates, and thus influences the pharmacokinetics of many drugs. Recent work,
      relying mainly on the use of Abcg2(-/-) mice, has revealed important
      contributions of ABCG2 to the blood-brain, blood-testis and blood-fetal barriers.
      Together, these functions indicate a primary biological role of ABCG2 in
      protecting the organism from a range of xenobiotics. In addition, several other
      physiological functions of ABCG2 have been observed, including extrusion of
      porphyrins and/or porphyrin conjugates from hematopoietic cells, liver and
      harderian gland, as well as secretion of vitamin B(2) (riboflavin) and possibly
      other vitamins (biotin, vitamin K) into breast milk. However, the physiological
      significance of these processes has been difficult to establish, indicating that
      there is still a lot to learn about this intriguing protein.

PMID- 19118590
TI  - Structural characterization of five post-translationally modified isomorphs of a
      novel putative delta-conotoxin from the vermivorous snail Conus delessertii from
      the Mexican Caribbean Sea.
AB  - A novel peptide, de7b, was isolated from the venom of Conus delessertii, a worm
      hunting species collected in the Caribbean Sea off the Yucatan Peninsula. Its
      primary structure was determined by automated Edman degradation and confirmed by
      mass spectrometry: it contains 28 amino acids, including six Cys residues.
      Peptide de7b is the second, O-conotoxin-like peptide isolated from the venom of
      this species, and it exists in different post-translationally modified isomorphs,
      some of which contain gamma-carboxy-glutamate (gamma) and/or 4-hydroxy-proline
      (O) at positions 4, 7, and/or 14. Its primary structure is
      DCI(P/O)GG(E/gamma)NCDVFR(O/P)YRCCSGYCILLLCA, with molecular masses varying from
      3078.6 to 3154.6Da, depending on the number and kind of modified amino acid
      residues. Peptide de7b shows significant sequence identity with several O
      conotoxins purified and biologically characterized from molluscivorous and
      piscivorous cone snails of the Indo-Pacific region, the tropical Atlantic and
      Eastern Pacific Oceans, especially with the delta-conotoxins but also with the
      omega-conotoxins from molluscivorous species, which suggests that it might affect
      voltage-gated Na(+) or Ca(2+)channels. Peptide de7b has 32% sequence identity
      with putative gamma-conotoxin de7a, previously characterized from the same
      species; both peptides contain the same number of amino acid residues and of non
      Cys residues between the pairs of consecutive Cys residues. However, these
      peptides have charge differences at seven positions within the N-terminal half
      indicating that they might have distinct molecular targets that remain to be
      identified.

PMID- 19118591
TI  - Electrophysiological effects of ghrelin on pedunculopontine tegmental neurons in
      rats: An in vitro study.
AB  - Ghrelin is a potent stimulant for growth hormone (GH) secretion and feeding.
      Recent studies further show a critical role of ghrelin in the regulation of sleep
      wakefulness. Pedunculopontine tegmental nucleus (PPT), which regulates waking and
      rapid eye movement (REM) sleep, expresses GH secretagogue receptors (GHS-Rs).
      Thus, the present study was carried out to examine electrophysiological effects
      of ghrelin on PPT neurons using rat brainstem slices, and to determine the ionic
      mechanism involved. Whole cell recording revealed that ghrelin depolarizes PPT
      neurons dose-dependently in normal artificial cerebrospinal fluid (ACSF). The
      depolarization persisted in tetrodotoxin-containing ACSF, although action
      potentials did not occur. Application of [d-Lys(3)]-GHRP-6, a selective
      antagonist for GHS-Rs, almost blocked the ghrelin-induced depolarization.
      Furthermore, the ghrelin-induced depolarization was reduced in high K(+) ACSF or
      low Na(+) ACSF, and abolished in high K(+)-low Na(+) ACSF or in a combination of
      low Na(+) ACSF and recordings with Cs(+)-containing pipettes. An inhibitor of
      Na(+)/Ca(2+) exchanger had no effect on the depolarization. Most of the PPT
      neurons recorded were characterized by an A-current or both the A-current and a
      low threshold Ca(2+) spike, and they were predominantly cholinergic as revealed
      by nicotinamide adenine dinucleotide phosphate-diaphorase staining. These results
      suggest that ghrelin depolarizes PPT neurons postsynaptically and dose
      dependently via GHS-Rs, and that the ionic mechanisms underlying the ghrelin
      induced depolarization include a decrease of K(+) conductance and an increase of
      non-selective cationic conductance. The results also support the notion that
      ghrelin plays a role in the regulation of sleep-wakefulness.

PMID- 19118592
TI  - Systemic administration of ghrelin increases extracellular dopamine in the shell
      but not the core subdivision of the nucleus accumbens.
AB  - The gut-hormone ghrelin endogenously binds to the ghrelin receptor (GHS-R) to
      promote foraging and feeding behaviours mainly via the hypothalamic arcuate
      nucleus (ARC). GHS-Rs are also expressed in midbrain dopaminergic neurons of the
      ventral tegmental area (VTA) suggesting that ghrelin may modulate the mesolimbic
      dopamine (DA) system. In support of this hypothesis, previous results have shown
      that intraventricular administration of ghrelin in rats increases DA levels in
      the nucleus accumbens (NAc). In the present study, the systemic doses of ghrelin
      capable of triggering central activation were first determined, and growth
      hormone (GH) levels were used as a marker of ghrelin-induced activation. Similar
      dose regimen was then used to measure ghrelin-induced effects on extracellular
      levels of monoamines in the shell and core subdivisions of the NAc using
      microdialysis in freely moving rats. We show that subcutaneous (s.c.)
      administration of ghrelin produced an increase in basal plasmatic ghrelin
      concentrations that was paralleled by enhanced GH secretion. In addition, a
      significant increase in extracellular levels of DA was observed specifically in
      the NAc shell, with no effect in the core subdivision. Extracellular serotonin (5
      HT) levels were also affected in the shell subregion, but without reaching
      statistical significance. Increased extracellular DA levels in the NAc shell have
      been typically associated with the acute reinforcing effects of addictive drugs.
      The present findings therefore suggest that systemic ghrelin may modulate the
      valence of reinforcers such as food and drugs of abuse by interfering with
      mesolimbic DA activity.

PMID- 19118593
TI  - Dual DNA vaccination of rainbow trout (Oncorhynchus mykiss) against two different
      rhabdoviruses, VHSV and IHNV, induces specific divalent protection.
AB  - DNA vaccines encoding the glycoprotein genes of the salmonid rhabdoviruses VHSV
      and IHNV are very efficient in eliciting protective immune responses against
      their respective diseases in rainbow trout (Oncorhynchus mykiss). The early anti
      viral response (EAVR) provides protection by 4 days post vaccination and is non
      specific and transient while the specific anti-viral response (SAVR) is long
      lasting and highly specific. Since both VHSV and IHNV are endemic in rainbow
      trout in several geographical regions of Europe and Atlantic salmon (Salmo salar)
      on the Pacific coast of North America, co-vaccination against the two diseases
      would be a preferable option. In the present study we demonstrated that a single
      injection of mixed DNA vaccines induced long-lasting protection against both
      individual and a simultaneous virus challenge 80 days post vaccination.
      Transfected muscle cells at the injection site expressed both G proteins. This
      study confirms the applied potential of using a combined DNA vaccination for
      protection of fish against two different rhabdoviral diseases.

PMID- 19118594
TI  - Model based analysis of hepatitis B vaccination strategies in the Netherlands.
AB  - We used a mathematical model for the transmission of hepatitis B infection to
      compare the effectiveness of different vaccination strategies in the Netherlands.
      Vaccination of children of immigrants from high and medium endemic countries is
      an effective strategy in countries with substantial immigration of carriers from
      high and medium endemic countries. A targeted vaccination programme for sexually
      highly active risk groups has a moderate additional effect if continued over a
      long time period. Universal vaccination has the largest effect on the incidence
      of new infections at the cost of having to vaccinate many more individuals than
      in targeted programmes. The impact on the prevalence of chronic hepatitis B
      infection, however, remains limited.

PMID- 19118595
TI  - Gene expression signatures in peripheral blood cells from Japanese women exposed
      to environmental cadmium.
AB  - The objective of this study was to examine the effects of environmental cadmium
      (Cd) exposure on the gene expression profile of peripheral blood cells, using an
      original oligoDNA microarray. The study population consisted of 20 female
      residents in a Cd-polluted area (Cd-exposed group) and 20 female residents in a
      non-Cd-polluted area individually matched for age (control group). The mRNA
      levels in Cd-exposed subjects were compared with those in respective controls,
      using a microarray containing oligoDNA probes for 1867 genes. Median Cd
      concentrations in blood (3.55 microg/l) and urine (8.25 microg/g creatinine) from
      the Cd-exposed group were 2.4- and 1.9-times higher than those of the control
      group, respectively. Microarray analysis revealed that the Cd-exposed group
      significantly up-regulated 137 genes and down-regulated 80 genes, compared with
      the control group. The Ingenuity Pathway Analysis Application (IPA) revealed that
      differentially expressed genes were likely to modify oxidative stress and
      mitochondria-dependent apoptosis pathways. Among differentially expressed genes,
      the expression of five genes was positively correlated with Cd concentrations in
      blood or urine. Quantitative real-time PCR (RT-PCR) analysis validated the
      significant up-regulation of CASP9, TNFRSF1B, GPX3, HYOU1, SLC3A2, SLC19A1,
      SLC35A4 and ITGAL, and down-regulation of BCL2A1 and COX7B. After adjustment for
      differences in the background characteristics of the two groups, we finally
      identified seven Cd-responsive genes (CASP9, TNFRSF1B, GPX3, SLC3A2, ITGAL,
      BCL2A1, and COX7B), all of which constituted a network that controls oxidative
      stress response by IPA. These seven genes may be marker genes useful for the
      health risk assessment of chronic low level exposure to Cd.

PMID- 19118596
TI  - Reversible hyperglycemia in rats following acute exposure to acephate, an
      organophosphorus insecticide: role of gluconeogenesis.
AB  - The present study was undertaken to investigate the hyperglycemic potential of
      acute exposure to acephate and its etiology employing rat model system. Oral
      administration of acephate (140mg/kg b.w.) caused reversible hyperglycemia as
      evidenced by peak increase in blood glucose at 2h after the administration (87%
      over control) followed by trend of normalization. In further experiment carried
      out to understand the etiology of the induced hyperglycemia, we observed that 2h
      exposure to acephate caused significant increase in blood glucose, plasma
      corticosterone (78%) and activities of two gluconeogenesis enzymes in liver viz.,
      glucose-6-phosphatase (91%) and tyrosine aminotransferase (84%) compared to that
      in control. When rats were exposed to acephate for 6h, decrement was observed in
      elevated levels of blood glucose, plasma corticosterone and the gluconeogenesis
      enzymes of the liver. Adrenal cholesterol levels in acephate-exposed rats were
      significantly depleted. While the glycogen content in liver of 2-h exposure group
      was comparable to control, a tremendous increase in liver glycogen content (
      approximately 3.5 folds) was observed in rats of the 6-h exposure group. Our
      results demonstrate that acephate causes reversible hyperglycemia in rats
      probably by enhancing hepatic glucose output via gluconeogenesis. A role for
      hyperactivity of adrenal cortex is suggested in increased gluconeogenesis while
      significant attenuation in elevated levels of blood glucose and the activity the
      gluconeogenesis enzyme, glucose-6-phosphatase in liver with concomitant increase
      in liver glycogen are indicative of the onset of counter-regulatory responses
      such as hyperinsulinemia, to overcome the induced hyperglycemia.

PMID- 19118597
TI  - Designing convergent cellular automata.
AB  - Cellular automata (CA) have been used by biologists to study dynamic non-linear
      systems where the interaction between cell behaviour and end-pattern is
      investigated. It is difficult to achieve convergence of a CA towards a specific
      static pattern and a common solution is to use genetic algorithms and evolve a
      ruleset that describes cell behaviour. This paper presents an alternative means
      of designing CA to converge to specific static patterns. A matrix model is
      introduced and analysed then a design algorithm is demonstrated. The algorithm is
      significantly less computationally intensive than equivalent evolutionary
      algorithms, and not limited in scale, complexity or number of dimensions.

PMID- 19118598
TI  - Neuroadaptations in the cellular and postsynaptic group 1 metabotropic glutamate
      receptor mGluR5 and Homer proteins following extinction of cocaine self
      administration.
AB  - This study examined the role of group1 metabotropic glutamate receptor mGluR5 and
      associated postsynaptic scaffolding protein Homer1b/c in behavioral plasticity
      after three withdrawal treatments from cocaine self-administration. Rats self
      administered cocaine or saline for 14 days followed by a withdrawal period during
      which rats underwent extinction training, remained in their home cages, or were
      placed in the self-administration chambers in the absence of extinction.
      Subsequently, the tissue level and distribution of proteins in the synaptosomal
      fraction associated with the postsynaptic density were examined. Cocaine self
      administration followed by home cage exposure reduced the mGluR5 protein in
      nucleus accumbens (NA) shell and dorsolateral striatum. While extinction training
      reduced mGluR5 protein in NAshell, NAcore and dorsolateral striatum did not
      display any change. The scaffolding protein PSD95 increased in NAcore of the
      extinguished animals. Extinction of drug seeking was associated with a
      significant decrease in the synaptosomal mGluR5 protein in NAshell and an
      increase in dorsolateral striatum, while that of NAcore was not modified.
      Interestingly, both Homer1b/c and PSD95 scaffolding proteins were decreased in
      the synaptosomal fraction after extinction training in NAshell but not NAcore.
      Extinguished drug-seeking behavior was also associated with an increase in the
      synaptosomal actin proteins in dorsolateral striatum. Therefore, extinction of
      cocaine seeking is associated with neuroadaptations in mGluR5 expression and
      distribution that are region-specific and consist of extinction-induced reversal
      of cocaine-induced adaptations as well as emergent extinction-induced
      alterations. Concurrent plasticity in the scaffolding proteins further suggests
      that mGluR5 receptor neuroadaptations may have implications for synaptic
      function.

PMID- 19118599
TI  - Imaging of phosphatidylcholines in the adult rat brain using MALDI-TOF MS.
AB  - Phosphatidylcholines (PCs) are the most abundant constituents of lipid in the
      brain. PCs function as major structural components of cell membranes and as
      important sources for signaling molecules. In the brain, three kinds of PCs,
      dipalmitoyl PC, palmitoyloleoyl PC, and stearoyloleoyl PC have been reported to
      be major species. They have different chemical and biological characteristics
      depending on the length of alkyl chains and the degree of saturation, suggesting
      that the abundance of PCs might be important to keep specialized membrane
      structures in the brain, such as myelin and synaptic membranes. However, detailed
      imaging of PCs in the total rat brain has not done yet. Thus, using imaging
      technology by matrix-assisted laser desorption/ionization mass spectrometry
      (MALDI-MS), we investigated the total distribution of PC32:0, PC34:1, and PC36:1
      in the rat brain. PC32:0 and PC34:1 were more abundantly observed in the gray
      matter areas than in the white matter areas throughout the central nervous system
      (CNS), while PC36:1 was evenly seen at low levels in both areas. In addition, we
      found that PC32:0 and PC34:1 were detected at very high levels in the granular
      layer of the olfactory bulb, piriform cortex, insular cortex, and molecular layer
      of the cerebellum, which are known for areas showing high neuronal plasticity.
      The present imaging data clearly show that various PCs are differentially
      distributed throughout the rat CNS, and suggest that these differential
      distributions of various PCs are necessary to keep normal brain functions.

PMID- 19118600
TI  - Expression of angiotensin II and its receptors in the normal and hypoxic amoeboid
      microglial cells and murine BV-2 cells.
AB  - Involvement of the local angiotensin receptor system in the central nervous
      system is well documented, yet its cellular localization and role in the glial
      cells have remained elusive. This study reports expression of angiotensin II and
      its receptors namely, angiotensin II receptor type 1 (AT(1)) and angiotensin II
      receptor type 2 (AT(2)) in the amoeboid microglial cells in the neonatal rat
      brain. In rats subjected to hypoxia, the amount of angiotensin II released in the
      corpus callosal tissue was reduced as revealed by enzyme immunoassay. Expression
      of AT(1) mRNA and protein was down-regulated after hypoxic exposure, but AT(2)
      was up-regulated. In BV-2 cells exposed to hypoxia for 4 h, expression of AT(1)
      mRNA was reduced but AT(2) was increased. These changes were further intensified
      respectively in LPS-stimulated microglia. Edaravone enhanced AT(1) expression but
      suppressed AT(2) expression significantly in lipopolysaccharide-stimulated cells.
      Neutralization of AT(2) with its antiserum significantly increased mRNA
      expression of tumor necrosis factor-alpha and interleukin-1beta but decreased
      that of transforming growth factor-beta1. In conclusion, the present results
      suggest that AT(1) may be linked to regulation of vasodilation for increase of
      blood flow in hypoxic conditions, while up-regulated expression of AT(2) may
      reduce inflammatory responses through suppression of proinflammatory cytokines
      and elimination of free radicals.

PMID- 19118601
TI  - Immunolocalization of alpha-synuclein in the rat spinal cord by two novel
      monoclonal antibodies.
AB  - This study provides the first immunohistochemical evidence of the presence and
      distribution patterns in the rat spinal cord of alpha-synuclein (alpha-Syn), a
      soluble acidic protein, widely expressed in the CNS and closely associated to the
      pathogenesis of neurodegenerative conditions such as Parkinson's and Alzheimer's
      diseases. We used two novel homemade monoclonal antibodies (2E3 and 3D5)
      recognizing two different epitopes of alpha-Syn. Both antibodies localized alpha
      Syn within the nerve terminals, whereas 3D5 alone also localized it within the
      neuronal nuclei. alpha-Syn-immunoreactive nervous elements were widely recognized
      throughout rat spinal cord and in almost all the gray matter laminae. However,
      they appeared particularly concentrated within laminae I, II, VII and X and more
      scattered in the others. Double immunofluorescent labeling showed that alpha-Syn
      colocalized with synaptophysin in the presynaptic nerve terminals, with
      neuropeptide Y (NPY) in lamina I, II, IX and X, and had close relationships with
      tyrosine hydroxylase (TH) immunoreactive neurons in laminae VII and X.
      Interestingly, the alpha-Syn-immunoreactive nerve elements, in lamina X,
      contained little of calbindin-28KD and calretinin-31KD. Our findings could help
      in understanding the genesis of some early clinical symptoms of Parkinson's
      disease (PD), such as pain and dysautonomic disorders, and indicate the spinal
      cord as their probable starting point, according to the ascending theory of PD,
      proposed by Braak.

PMID- 19118602
TI  - Putative neuroprotective role of centrally administered corticotropin-releasing
      factor in low-temperature-exposed neonatal chicks.
AB  - Corticotropin-releasing factor (CRF) modulates the activity of the hypothalamic
      pituitary-adrenal axis, and has a key role in mediating neuroendocrine effects
      that occur in response to stressful stimuli. We have recently shown that exposure
      of neonatal chicks to low-temperature resulted in increased oxidative damage to
      the brain and i.c.v. injection of CRF increased homeothermy that was associated
      with tissue specific enhancement of mitochondrial fatty acid oxidation enzyme
      activities. These observations prompted an investigation into the potential role
      of CRF in a state of oxidative damage in the brain and other vital organs in low
      temperature-exposed chicks. In the first experiment, neonatal chicks (Gallus
      gallus) were given i.c.v. injection of CRF (42 pmol) or saline and were then
      exposed to low-temperature (20 degrees C) for 3 h. Malondialdehyde (MDA) levels
      were measured in the plasma, brain, heart and skeletal muscle. In the second
      experiment, to confirm the modulatory role of CRF in the brain oxidative damage,
      as observed in the first experiment, neonatal chicks were given the i.c.v.
      injection of CRF (42 pmol), astressin (6 nmol, CRF receptor antagonist), or CRF
      (42 pmol) plus astressin (6 nmol) in combination, and were then exposed to low
      temperature (20 degrees C) for 3 h. CRF significantly decreased the weight gain
      and feed consumption of chicks that were recovered by astressin. In the plasma,
      significantly higher MDA levels were observed in i.c.v. CRF chicks exposed to low
      temperature, but this pattern was not observed in the brain, heart and skeletal
      muscle. Brain MDA levels in i.c.v. CRF chicks were decreased as compared with
      that of i.c.v. saline chicks on low-temperature exposure while i.c.v. astressin
      increased the MDA levels. In conclusion, CRF plays a putative neuroprotective
      role in the brain of low-temperature-exposed neonatal chicks.

PMID- 19118603
TI  - Kv1.1 expression in microglia regulates production and release of proinflammatory
      cytokines, endothelins and nitric oxide.
AB  - Potassium channels play an important role in microglial activation but their
      involvement in main functions of microglia including secretion of proinflammatory
      cytokines has remained uncertain. This study has revealed the specific expression
      of Kv1.1 in microglia both in vivo and in vitro. Kv1.1 immunoreactivity was
      localized in the amoeboid microglia in the rat brain between postnatal (P) day 1
      (P1) and day 10 (P10); it was, however, progressively reduced with age and was
      hardly detected at P14 and P21 in ramified microglia, a derivative cell of
      amoeboid microglia. Following hypoxic exposure, Kv1.1 expression in amoeboid
      microglia was enhanced or induced in ramified microglia in more mature brain at
      P21 when compared with their matching controls. RT-PCR and Western blot analysis
      confirmed Kv1.1 mRNA and protein expression in murine BV-2 cells which was up
      regulated by hypoxia or lipopolysaccharide (LPS) treatment; it was reduced
      significantly by dexamethasone. Neutralization with Kv1.1 antibody suppressed the
      expression and release of tumor necrosis factor-alpha, interleukin-1beta,
      endothelins and nitric oxide (NO) in LPS-activated BV-2 cells. It is concluded
      that Kv1.1, constitutively expressed by microglia, is elicited by hypoxia and LPS
      and this may be linked to production of proinflammatory cytokines, endothelins
      and NO.

PMID- 19118605
TI  - Structure elucidation and complete NMR spectral assignment of two triterpenoid
      saponins from Radix Hedysari.
AB  - A new oleanane-type triterpenoid saponin with a carbonyl group at C-15, named
      polybosaponin A (1), together with a known triterpenoid saponin,
      dehydrosoyasaponin I (2), were isolated from Radix Hedysari. On the basis of one-
      and two-dimensional NMR and high resolution electrospray ionization mass
      spectrometry, the structure of 1 were elucidated and the (1)H and (13)C NMR
      spectral signals were assigned totally. In addition, the complete assignment of
      (1)H NMR signals and revision of incorrect assignment of (13)C NMR signals for 2
      were also achieved based on one- and two-dimensional NMR spectrometry.

PMID- 19118604
TI  - Neurotensin inversely modulates maternal aggression.
AB  - Neurotensin (NT) is a versatile neuropeptide involved in analgesia, hypothermia,
      and schizophrenia. Although NT is released from and acts upon brain regions
      involved in social behaviors, it has not been linked to a social behavior. We
      previously selected mice for high maternal aggression (maternal defense), an
      important social behavior that protects offspring, and found significantly lower
      NT expression in the CNS of highly protective females. Our current study directly
      tested NT's role in maternal defense. Intracerebroventricular (i.c.v.) injections
      of NT significantly impaired defense in terms of time aggressive and number of
      attacks at all doses tested (0.05, 0.1, 1.0, and 3.0 microg). Other maternal
      behaviors, including pup retrieval, were unaltered following NT injections (0.05
      microg) relative to vehicle, suggesting specificity of NT action on defense.
      Further, i.c.v. injections of the NT receptor 1 (NT1) antagonist, SR 48692 (30
      microg), significantly elevated maternal aggression in terms of time aggressive
      and attack number. To understand where NT may regulate aggression, we examined
      Fos following injection of either 0.1 microg NT or vehicle. Thirteen of 26 brain
      regions examined exhibited significant Fos increases with NT, including regions
      expressing NT1 and previously implicated in maternal aggression, such as lateral
      septum, bed nucleus of stria terminalis, paraventricular nucleus, and central
      amygdala. Together, our results indicate that NT inversely regulates maternal
      aggression and provide the first direct evidence that lowering of NT signaling
      can be a mechanism for maternal aggression. To our knowledge, this is the first
      study to directly link NT to a social behavior.

PMID- 19118606
TI  - The evolution of two partner LINE/SINE families and a full-length chromodomain
      containing Ty3/Gypsy LTR element in the first reptilian genome of Anolis
      carolinensis.
AB  - Transposable elements have been characterized in a number of vertebrates,
      including whole genomes of mammals, birds, and fishes. The Anolis carolinensis
      draft assembly provides the first opportunity to study retroposons in a reptilian
      genome. Here, we identified and reconstructed a number of retroposons based on
      database searches: Five Sauria short interspersed element (SINE) subfamilies, 5S
      Sauria SINE chimeras, Anolis Bov-B long interspersed element (LINE), Anolis SINE
      2, Anolis LINE 2, Anolis LINE 1, Anolis CR 1, and a chromodomain-containing
      Ty3/Gypsy LTR element. We focused on two SINE families (Anolis Sauria SINE and
      Anolis SINE 2) and their partner LINE families (Anolis Bov-B LINE and Anolis LINE
      2). We demonstrate that each SINE/LINE pair is distributed similarly and predict
      that the retrotransposition of evolutionarily younger Sauria SINE members is via
      younger Bov-B LINE members while a correlation also exists between their
      respective evolutionarily older SINE/LINE members. The evolutionarily youngest
      Sauria SINE sequences evolved as part of novel rolling-circle transposons. The
      evolutionary time frame when Bov-B LINEs and Sauria SINEs were less active in
      their retrotransposition is characterized by a high retrotransposition burst of
      Anolis SINE 2 and Anolis LINE 2 elements. We also characterized the first full
      length chromoviral LTR element in amniotes (Amn-ichi). This newly identified
      chromovirus is widespread in the Anolis genome and has been very well preserved,
      indicating that it is still active. Transposable elements in the Anolis genome
      account for approximately 20% of the total DNA sequence, whereas the proportion
      is more than double that in many mammalian genomes in which such elements have
      important biological functions. Nevertheless, 20% transposable element coverage
      is sufficient to predict that Anolis retroposons and other mobile elements also
      may have biologically and evolutionarily relevant functions. The new SINEs and
      LINEs and other ubiquitous genomic elements characterized in the Anolis genome
      will prove very useful for studies in comparative genomics, phylogenetics, and
      functional genetics.

PMID- 19118607
TI  - Catalytic activity-independent pathway is involved in phospholipase A(2)-induced
      apoptotic death of human leukemia U937 cells via Ca(2+)-mediated p38 MAPK
      activation and mitochondrial depolarization.
AB  - In view of the controversial role of catalytic activity on the cytotoxicity of
      phospholipase A(2) (PLA(2)), the present study is conducted to explore whether
      PLA(2) induces apoptotic process of human leukemia U937 cells through catalytic
      activity-independent pathway. Modification of His-48 (according to the sequence
      alignment with porcine pancreatic PLA(2)) with p-bromophenacyl bromide (BPB)
      caused over 99.9% drop in enzymatic activity Naja naja atra PLA(2). It was found
      that BPB-PLA(2)-induced apoptotic death of U937 cells was associated with
      mitochondrial depolarization, modulation of Bcl-2 family members, cytochrome c
      release and activation of caspases 9 and 3. Upon exposure to BPB-PLA(2),
      elevation of intracellular Ca(2+) levels and p38 MAPK activation were observed in
      U937 cells. Pretreatment with BAPTA-AM (Ca(2+) chelator) and nifedipine (L-type
      Ca(2+) channel blocker) abrogated Ca(2+) increase and p38 MAPK activation, and
      rescued viability of BPB-PLA(2)-treated U937 cells. BPB-PLA(2)-induced
      dissipation of mitochondrial membrane potential and down-regulation of Bcl-2 were
      suppressed by SB202190 (p38MAPK inhibitor). Although PLA(2) mutants in which His
      48 and Asp-49 were substituted by Ala and Lys, respectively, did not display
      detectable PLA(2) activity, they induced death of U937 cells. The signaling
      pathway of PLA(2) mutants in inducing cell death was indistinguishable from that
      of BPB-PLA(2). Taken together, our data indicate that catalytic activity
      independent pathway is involved in PLA(2)-induced apoptotic death of human
      leukemia U937 cells via mitochondria-mediated death pathway triggering by Ca(2+)
      mediated p38 MAPK activation.

PMID- 19118608
TI  - Toxicology of engineered nanomaterials - introduction.

PMID- 19118609
TI  - Pharmaceuticals in the environment: good practice in predicting acute
      ecotoxicological effects.
AB  - Improvements in analytical techniques have led to an increased awareness of the
      presence of pharmaceuticals in the environment. Concern is now raised as to the
      potential adverse effects these compounds may have on non-target organisms,
      particularly under conditions of chronic exposure. There is a paucity of
      experimental ecotoxicity data available for pharmaceuticals, hence the use of in
      silico tools to predict toxicity is a pragmatic option. Previous studies have
      used the ECOSAR program to predict environmental toxicity of pharmaceuticals,
      however, these models were developed using industrial chemicals and the
      applicability of the models to predict effects of pharmaceuticals should be
      carefully considered. In this study ECOSAR was used to assign 364 diverse
      pharmaceuticals to recognised chemical classes and hence predict their aquatic
      toxicity. Confidence in the predictions was assessed in terms of whether the
      assigned class was realistically representative of the pharmaceutical in
      question. The correlation between experimentally determined toxicity values
      (where these were available) and those predicted by ECOSAR was investigated in
      terms of confidence in the prediction. ECOSAR was shown to make reasonable
      predictions for certain pharmaceuticals considered to be within the applicability
      domain of the models, but predictions were less reliable for compounds judged to
      fall outwith the domain of the models. This study is not critical of ECOSAR or
      the class based approach to predicting toxicity, but demonstrates the importance
      of using expert judgement to ascertain whether or not use of a particular model
      is appropriate when the specific chemistry of a query compound is considered.

PMID- 19118610
TI  - Endocrine effects of hexabromocyclododecane (HBCD) in a one-generation
      reproduction study in Wistar rats.
AB  - The brominated flame retardant (BFR) hexabromocyclododecane was tested in a one
      generation reproduction assay in Wistar rats, enhanced for endocrine parameters.
      A solution of the compound in corn oil was mixed in the feed, targeting at
      dietary exposure of 0-0.1-0.3-1-3-10-30-100 mg/kg body weight/day (mkd) in
      parental rats during 10 (males) or 2 (females) weeks premating, during gestation
      and lactation, and in their F1 offspring from weaning until final necropsy.
      Effects were assessed in F1 animals. Livers of these animals showed increased
      HBCD concentrations, in a dose-dependent way. The trabecular bone mineral density
      of the tibia was dose-dependently decreased in females (BenchMark Dose Lower
      confidence bound, BMDL=0.056 mkd). The IgG response after immunization with sheep
      red blood cells (SRBC) was increased in males (BMDL=0.46 mkd). Further sensitive
      effects were decreased weight of the testis (BMDL=1.5 mkd), increased fraction of
      neutrophilic granulocytes (BMDL=7.7 mkd), decreased concentration of apolar
      retinoids in female livers (BMDL=1.3 mkd), and decreased plasma alkaline
      phosphatase in females (BMDL=8.6 mkd). CYP19/aromatase activity in the ovary was
      correlated to the concentration of gamma-HBCD in the liver. A developmental
      origin of these effects is considered, and this is also true for sensitive
      effects observed in neurobehavioural testing in littermates from the same
      experiment, i.e. in the brainstem auditory evoked potentials and in a catalepsy
      test [Lilienthal, H., Van der Ven, L.T.M., Piersma, A.H., Vos, J.G.
      Neurobehavioral effects of the brominated flame retardant hexabromocyclododecane
      (HBCD) in rats after pre- and postnatal exposure, in press]. The low BMDLs of
      these effects may raise concern for human health, particularly when based on body
      burdens of HBCD, which leads to critical margins of exposure particularly for the
      occupational setting.

PMID- 19118611
TI  - Characterization of the inhibition of breast cancer resistance protein-mediated
      efflux of mitoxantrone by pharmaceutical excipients.
AB  - Previously we showed that some excipients can inhibit breast cancer resistance
      protein (BCRP/ABCG2) in vitro and in vivo. We then evaluated the reversibility
      and the mode of BCRP inhibition of excipients, such as Tween 20 and Pluronic P85,
      by the intracellular mitoxantrone uptake study. To evaluate the reversibility of
      BCRP inhibitory effects, BCRP expressing cells were preincubated with the
      excipients and the intracellular mitoxantrone uptake was determined after
      removing or not removing the excipients. To evaluate the mode of BCRP inhibitory
      effects, the intracellular mitoxantrone uptake at the different mitoxantrone
      concentrations in the medium with the excipients was determined. Both Tween 20
      and Pluronic P85 increased the mitoxantrone uptake in BCRP expressing cells, but
      these effects were disappeared when the excipients were removed. Moreover, both
      excipients increased the uptake at low substrate concentrations. However, at high
      substrate concentrations, Tween 20 increased the uptake to less extent compared
      with low substrate concentrations, whereas there was no such effect of Pluronic
      P85. Taken together, Pluronic P85 and Tween 20 appear to inhibit BCRP-mediated
      efflux of mitoxantrone reversibly and the inhibition mode of Pluronic P85 may be
      competitive but not that of Tween 20, which may be mixed type.

PMID- 19118612
TI  - Novel drug delivery devices for providing linear release profiles fabricated by
      3DP.
AB  - Novel doughnut-shaped multi-layered drug delivery devices (DDDs) were developed
      with local variations of the drug and release-retardant material for providing
      linear release profiles. Based on computer-aided design models, different DDDs
      containing acetaminophen as a model drug, hydroxypropyl methylcellulose as matrix
      and ethyl cellulose (EC) as a release-retardant material were prepared
      automatically using a three-dimensional printing (3DP) system. In vitro
      dissolution assays demonstrated that all the 3DP DDDs had with different
      diameters, heights, concentrations of EC and central hole diameters were able to
      give linear release profiles. Morphological and erosion studies showed that
      acetaminophen was released through a simultaneous surface erosion process
      involving the outer peripheries and inner apertures. The barrier layers on both
      bases of DDDs had good adhesion strength with the drug-contained regions and
      offered consistent release retardation for the whole duration of the dissolution
      process. The release time periods of the DDDs were dependent on the annular
      thicknesses or the passes of binder solution containing a release-retardant
      material. The dosage of the DDD can be adjusted independently by changing the
      heights of the DDDs. Thus, 3DP is capable of offering novel strategies for
      developing DDDs with complex design features for desired drug release profiles.

PMID- 19118613
TI  - Overcome side identification in PPOP by making orifices on both layers.
AB  - The original purpose of this research was to build a database for an expert
      system. Unexpectedly, it was found that the color-identifying device in push-pull
      osmotic pump (PPOP) manufacturing process could be unnecessary. Water-insoluble
      drug indapamide, gliclazide and dipyridamole were employed as model drugs.
      Bunches of conventional formulations were designed; and traditional preparation
      procedures were used. In vitro drug release was studied; and the similarity
      between the conditions of orifice only on the side of the drug layer and orifices
      of the same diameter on both sides was evaluated. It was found that the drug
      release from PPOP could be influenced by formulation and core hardness while it
      could hardly be influenced by orifice size. No significant difference was
      observed between the dissolution profiles of orifice only on the side of the drug
      layer and orifices of the same diameter on both sides. Mechanism of drug release
      was discussed. The conclusion was that the disadvantage of side identification in
      PPOP manufacturing process could be overcome by drilling orifices on both sides.

PMID- 19118614
TI  - Enhanced electrostatic interaction between chitosan-modified PLGA nanoparticle
      and tumor.
AB  - In our previous study, lung tumor-specific targeting of paclitaxel was achieved
      in mice by intravenous administration of chitosan-modified paclitaxel-loaded PLGA
      nanoparticles (C-NPs-paclitaxel). Transient formation of aggregates in the blood
      stream followed by enhanced trapping in the capillaries was proposed as a
      mechanism of the lung-specific accumulation of paclitaxel. In the present study,
      the mechanism of tumor lung preferential accumulation of paclitaxel from C-NPs
      paclitaxel was investigated. Zeta potential and in vitro cellular cytotoxicity
      (A549 cells and CT-26 cells) of C-NPs-paclitaxel, and in vitro uptake of coumarin
      6 to these cells from chitosan-modified coumarin 6 containing PLGA nanoparticles
      (C-NPs-coumarin 6) were examined as a function of pH (6.8, 7.4 and 8.0). The zeta
      potential of C-NPs-paclitaxel increased as the medium pH became more acidic. In
      vitro uptake of coumarin 6 by A549 cells and CT-26 cells was enhanced at lower pH
      for C-NPs-coumarin 6. In vitro cytotoxicity experiment with C-NPs-paclitaxel
      demonstrated enhanced cytotoxicity as the pH became more acidic. Therefore,
      enhanced electrostatic interaction between chitosan-modified PLGA nanoparticles
      and acidic microenvironment of tumor cells appears to be an underlying mechanism
      of lung tumor-specific accumulation of paclitaxel from C-NPs-paclitaxel.

PMID- 19118615
TI  - Antiurolithic effect of Bergenia ligulata rhizome: an explanation of the
      underlying mechanisms.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: Bergenia ligulata is widely used plant in South
      Asia, mainly India and Pakistan, as a traditional medicine for treatment of
      urolithiasis. AIM OF THE STUDY: To rationalize the Bergenia ligulata use in
      kidney stones and to explain the underlying mechanisms. MATERIALS AND METHODS:
      The crude aqueous-methanolic extract of Bergenia ligulata rhizome (BLR) was
      studied using in vitro and in vivo methods. RESULTS: BLR inhibited calcium
      oxalate (CaC(2)O(4)) crystal aggregation as well as crystal formation in the
      metastable solutions and exhibited antioxidant effect against 1,1-diphenyl-2
      picrylhydrazyl free radical and lipid peroxidation in the in vitro. BLR caused
      diuresis in rats accompanied by a saluretic effect. In an animal model of
      urolithiasis, developed in male Wistar rats by adding 0.75% ethylene glycol (EG)
      in drinking water, BLR (5-10 mg/kg) prevented CaC(2)O(4) crystal deposition in
      the renal tubules. The lithogenic treatment caused polyuria, weight loss,
      impairment of renal function and oxidative stress, manifested as increased
      malondialdehyde and protein carbonyl contents, depleted reduced glutathione and
      decreased antioxidant enzyme activities of the kidneys, which were prevented by
      BLR. Unlike the untreated animals, EG intake did not cause excessive
      hyperoxaluria and hypocalciuria in BLR treated groups and there was a significant
      increase in the urinary Mg(2+), instead of a slight decrease. CONCLUSIONS: These
      data indicate the antiurolithic activity in Bergenia ligulata mediated possibly
      through CaC(2)O(4) crystal inhibition, diuretic, hypermagneseuric and antioxidant
      effects and this study rationalizes its medicinal use in urolithiasis.

PMID- 19118616
TI  - Carbon tetrachloride-induced nephrotoxicity in rats: protective role of Digera
      muricata.
AB  - Digera muricata is used in renal disorders in folk medicine. Generation of
      reactive radicals has been implicated in carbon tetrachloride-induced
      nephrotoxicity, which are involved in lipid peroxidation, accumulation of
      dysfunctional proteins, leading to injuries in kidneys. The present study was
      aimed to evaluate the efficacy of Digera muricata on the kidney function in
      CCl(4)-induced injuries. CCl(4) treatment (5 ml/kg body wt., i.p. CCl(4):olive
      oil; 1:9) significantly increased the level of urine creatinine, protein,
      nitrite, urobilinogen, red blood cells (RBCs), leucocytes count, and levels of
      blood urea nitrogen (BUN). Level of proteins and DNA fragmentation %,
      argyrophilic nucleolar organizer regions (AgNORs) count in renal tissues was also
      significantly increased. Activity of antioxidant enzymes; catalase, peroxidase,
      superoxide dismutase and reduced glutathione (GSH) were decreased while
      thiobarbituric acid reactive substances (TBARSs) were increased with CCl(4)
      treatment. DNA ladder assay was intimately related with the DNA fragmentation
      assay. Telomerase activity was determined in the CCl(4)-treated renal tissue
      homogenate. Treatment with n-hexane (HDMP) and methanolic (MDMP) extracts of
      Digera muricata (200 and 250 mg/kg body wt., oral, respectively) effectively
      attenuated the alterations in the biochemical markers, telomerase activity was
      inhibited and confirms the restoration of normalcy and accredits the protective
      role of Digera muricata against CCl(4)-induced nephrotoxicity.

PMID- 19118617
TI  - Treatment of perennial allergic rhinitis using Shi-Bi-Lin, a Chinese herbal
      formula.
AB  - AIM OF THE STUDY: Shi-Bi-Lin (SBL) is modified from the classic formula Cang-Er
      Zi-San which has been used to treat chronic rhinitis, paranasal sinusitis and
      allergic rhinitis by herbal practitioners. The present study aimed at patients
      with moderate to severe perennial allergic rhinitis. SBL which has been shown
      effective in treating a guinea-pig model of allergic rhinitis, was evaluated for
      its efficacy and safety. MATERIALS AND METHODS: 126 allergic rhinitis patients
      were recruited in a double-blind randomized control trial. Half of the patients
      received SBL capsules and the others half received placebo for 4 weeks. Symptoms
      scores, physician's evaluation, nose examination, quality of life, adverse
      effects, serum cytokines were evaluated before and after treatment. RESULTS: SBL
      was found to be safe and effective in relieving some symptoms of perennial
      allergic rhinitis, improving the nose condition, and enhancing some domains of
      quality of life when compare to placebo, (p<0.05). In the 2 weeks follow up after
      treatment completion, the SBL enjoyed a prolongation of symptom control (p=0.05).
      CONCLUSION: SBL relieved symptoms of nose blockage among patients with perennial
      allergic rhinitis, and some aspects of the quality of life were also improved.
      The improvement was sustained for at least 2 weeks after treatment. No serious
      adverse events were encountered.

PMID- 19118618
TI  - WITHDRAWN: Prenatal exposure to MDMA induces sex-dependent and region-specific
      modifications in brain dopamine systems at adult age in the rat.
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- 19118619
TI  - Sophora flavescens Aiton inhibits the production of pro-inflammatory cytokines
      through inhibition of the NF kappaB/IkappaB signal pathway in human mast cell
      line (HMC-1).
AB  - The dried roots of Sophora flavescens Aiton (SFA) has been used in traditional
      medicine for treatment of inflammation, gastrointestinal hemorrhage, diarrhea,
      and asthma. In the present study, we investigated the effect of SFA on the
      inflammatory allergic reaction using human mast cell-1 (HMC-1). SFA (200mg/kg)
      inhibited the mast cell-mediated passive cutaneous anaphylaxis reaction in vivo
      and the release of histamine from rat peritoneal mast cells by compound 48/80. In
      addition, the expression levels of phorbol 12-myristate 13-acetate (PMA) and
      calcium ionophore A23187-stimulated TNF-alpha, IL-6, and IL-8 were also decreased
      by SFA treatment. In molecular mechanism level, this study showed that SFA
      inhibited the nuclear translocation of nuclear factor (NF) kappaB through
      inhibition of the phosphorylation and degradation of IkappaB-alpha, which is an
      inhibitor of NF kappaB. Moreover, SFA suppressed PMA plus A23187-induced
      phosphorylation of the mitogen-activated protein kinase p38 and c-jun N-terminal
      kinase. The inhibited induction of NF kappaB promoter by SFA was determined using
      luciferase activity. These results suggest that SFA could be used as a treatment
      for mast cell-derived allergic inflammatory diseases.

PMID- 19118620
TI  - Alteration of testicular steroidogenesis and histopathology of reproductive
      system in male rats treated with triclosan.
AB  - Triclosan (TCS), a chlorophenol, is widely used as a preservative in different
      types of commercial preparations. The reports on TCS-mediated endocrine
      disruption are controversial and the present study aimed to elucidate the
      probable mode of action of TCS as an antiandrogenic compound using a robust study
      design. Male albino rats, Rattus norvegicus, were treated with three doses of
      triclosan for a period of 60 days followed by the analysis of various biochemical
      parameters. RT-PCR analysis demonstrated a significant decrease in mRNA levels
      for testicular steroidogenic acute regulatory (StAR) protein, cytochrome
      P450(SCC), cytochrome P450(C17), 3beta-hydroxysteroid dehydrogenase (3beta-HSD),
      17beta-hydroxysteroid dehydrogenase (17beta-HSD) and androgen receptor (AR) in
      TCS treated rats (p<0.05). TCS also induced a perturbed translation of testicular
      StAR, and AR proteins as shown by Western blot analysis in treated groups of
      rats. A reduced level of StAR was further indicated by immunohistochemistry in
      testicular Leydig cells. Further, there was a significant decrease (p<0.05) in
      the level of serum lutenizing hormone (LH), follicle stimulating hormone (FSH),
      cholesterol, pregnenolone, and testosterone. In vitro assays demonstrated more
      than 30% decrease in testicular 3beta-HSD and 17beta-HSD enzyme activities in
      treated group of animals. Extensive histopathological malformations were observed
      in the testis and sex accessory tissues of the treated rats. Overall this study
      showed that TCS decreased the synthesis of androgens followed by reduced sperm
      production in treated male rats which could be mediated by a decreased synthesis
      of LH and FSH thus involving hypothalamo-pituitary-gonadal axis.

PMID- 19118621
TI  - G proteins in rat prefrontal cortex (PFC) are differentially activated as a
      function of oxygen status and PFC region.
AB  - This study tested the hypothesis that activation of guanine nucleotide binding
      (G) proteins in rat prefrontal cortex (PFC) is altered by hypoxia. G protein
      activation by the cholinergic agonist carbachol and the opioid agonist DAMGO was
      quantified using [(35)S]GTPgammaS autoradiography. G protein activation was
      expressed as nCi/g tissue in the PFC of 18 rats exposed for 14 consecutive days
      to sustained hypoxia (10% O(2)), intermittent hypoxia (10% and 21% O(2)
      alternating every 90 s), or room air (21% O(2)). Relative to basal levels of G
      protein activation, carbachol and DAMGO increased G protein activation by
      approximately 70% across all oxygen concentrations. Compared to the room air
      condition, sustained hypoxia caused a significant increase in G protein
      activation in frontal association (FrA) region of the PFC. Region-specific
      comparisons revealed that intermittent and sustained hypoxia caused greater DAMGO
      stimulated G protein activation in the FrA than in the pre-limbic (PrL). The data
      show for the first time that hypoxia increased G protein activation in PFC. The
      results suggest the potential for hypoxia-induced enhancements in G protein
      activation to alter PFC function.

PMID- 19118622
TI  - Expression of mu- and delta-opioid receptors in song control regions of adult
      male zebra finches (Taenopygia guttata).
AB  - The opioid system is known to play a role in various aspects of learning and
      memory in diverse species of mammals and birds. Earlier studies have localized
      the endogenous opioids, met- and leu-enkephalin, in the song control regions of
      male zebra finches (Taenopygia guttata), a sexually dimorphic species of
      songbirds wherein only males sing. Recent research has shown that levels of
      enkephalin increase in some of the song control regions during singing and that
      blocking opioid receptors with the antagonist naloxone decreases the frequency of
      singing in songbirds. However, the distribution of receptors specific to the
      opioid system has not been studied in zebra finches. In the present study, we
      used reverse transcriptase PCR (RT-PCR) and quantitative real-time PCR (qRT-PCR)
      to demonstrate that the song control regions lateral magnocellular nucleus of the
      anterior nidopallium (LMAN), Area X, MSt (medial striatum), HVC and RA (robust
      nucleus of the arcopallium) expressed higher levels of mu-OR mRNA compared to
      delta-OR mRNA. In situ hybridization was used to demonstrate that neither LMAN
      nor Area X could be delineated from the surrounding brain regions [anterior
      nidopallium (ANP) and MSt, respectively], based on OR mRNA expression. However,
      HVC and RA neurons expressed marginally higher levels of mu-OR mRNA compared to
      the posterior nidopallium, which was confirmed by immunohistochemical
      localization. We also found that the dorsolateral subdivision of DLM
      (dorsolateral nucleus of the medial thalamus) demonstrated high levels of mu-OR
      immunoreactivity. Our results suggest that the ORs may be involved in modulating
      different aspects of vocalization and/or gating auditory input, as well as motor
      control.

PMID- 19118623
TI  - Glutathione depletion in immortalized midbrain-derived dopaminergic neurons
      results in increases in the labile iron pool: implications for Parkinson's
      disease.
AB  - Glutathione depletion is one of the earliest detectable events in the
      Parkinsonian substantia nigra (SN), but whether it is causative for ensuing
      molecular events associated with the disease is unknown. Here we report that
      reduction in levels of glutathione in immortalized midbrain-derived dopaminergic
      neurons results in increases in the cellular labile iron pool (LIP). This
      increase is independent of either iron regulatory protein/iron regulatory element
      (IRP/IRE) or hypoxia inducible factor (HIF) induction but is both H(2)0(2) and
      protein synthesis-dependent. Our findings suggest a novel mechanistic link
      between dopaminergic glutathione depletion and increased iron levels based on
      translational activation of TfR1. This may have important implications for
      neurodegeneration associated with Parkinson's disease in which both glutathione
      reduction and iron elevation have been implicated.

PMID- 19118624
TI  - S100beta upregulation: a possible mechanism of deltamethrin toxicity and motor
      coordination deficits.
AB  - Deltamethrin (DLT) is a type II synthetic pyrethroid with insecticidal
      properties. It has been considered safe to humans. Excessive exposure of DLT is
      being variously reported, recently, to cause potential neurotoxicity in adults,
      as characterized by ataxia, loss of coordination, hyperexcitability, convulsions
      and paralysis. However, limited information is available on its impact at
      lower/safe to human doses during development. The present study was designed to
      assess the postnatal (P) exposure of DLT (as low as 0.7 mg/kg, i.p.) on S-100beta
      expression in developing rat cerebellum and its impact on Purkinje cell
      morphogenesis and dendritogenesis, and subsequent spontaneous motor activity
      (SMA) deficits. Wistar rat pups born to healthy mothers were injected with DLT
      (Sigma) at a dosage of 0.7 mg/kg body wt., i.p. dissolved in DMSO (Sigma) during
      P0-7th (DLT-I) and P9-13th day (DLT-II). The control pups were injected with
      equivalent volumes of DMSO. The pups of both the groups were used to assess the
      spontaneous motor activity P21 onwards. The cryocut sections (30 microm) of the
      cerebella were used for anti-S-100beta antibody labeling using streptavidin
      biotin HRP method. An upregulation of S-100beta expression in Bergmann glial
      fibers was recorded at P12 and P15 day preparations in both DLT-I and DLT-II
      treated groups. However, such upregulation of S-100beta was more prominent in DLT
      II treated group animals with a large number of strongly S-100beta immunopositive
      astrocytes flanking around the Purkinje neurons. In Golgi preparation the
      Purkinje neurons in DLT treated groups had reduced dendritic arbor with short
      primary dendrites and much reduced dendritic branches which appeared stumpy and
      hypertrophied. The granule cell proliferation and migration as well as Purkinje
      cell morphogenesis and dendritogenesis are affected following DLT exposure in the
      present investigation. This may also affect the mossy fiber-granule cell-parallel
      pathway formation which in turn may decrease the firing of Purkinje cells
      (GABAergic inhibitory projections) and thus an increase in the output of the
      neurons in the deep cerebellar nuclei neurons and disturbed motor coordination.

PMID- 19118625
TI  - Dpp of posterior origin patterns the proximal region of the wing.
AB  - The decapentaplegic (dpp) gene encodes a long-range morphogen that plays a key
      role in the patterning of the wing imaginal disc of Drosophila (Nellen, D.,
      Burke, R., Struhl, G. and Basler, K. 1996. Direct and long-range action of a DPP
      morphogen gradient. Cell 85, 357-368.). The current view is that dpp is
      transcriptionally active in a narrow band of anterior compartment cells close to
      the anterio-posterior (A/P) compartment border. Once the Dpp protein is
      synthesised, it travels across the A/P border and diffuses forming concentration
      gradients in the two compartments (reviewed in Lawrence, P.A., Struhl, G. 1996.
      Morphogens, compartments, and pattern: lessons from drosophila? Cell 85, 951
      961.). We have found a new site of dpp expression in the posterior wing
      compartment which appears during the third larval period. This source of Dpp
      signal generates a local gradient of Dpp pathway activity, which is independent
      of that originating in the anterior compartment. We show that this posterior tier
      of Dpp activity is functionally required for normal wing development: the
      elimination of dpp expression in the posterior compartment results in defective
      adult wings in which pattern elements such as the alula and much of the axillary
      cord are not formed. Moreover, these structures develop normally in the absence
      of anterior dpp expression. Thus the normal wing pattern requires distinct Dpp
      organizer activities in the anterior and posterior compartments. We further show
      that, unlike the anterior dpp expression domain, the posterior one is not
      dependent on Hedgehog activity but is dependant on the activity of the IRO
      complex gene mirror. Since there is a similar expression in the haltere disc, we
      suggest that this late appearing posterior Dpp activity may be an attribute of
      dorsal thoracic discs.

PMID- 19118626
TI  - Non-invasive in vivo methods for investigation of the skin barrier physical
      properties.
AB  - Skin as an organ of protection covers the body and accomplishes multiple
      defensive functions. The intact skin represents a barrier to the uncontrolled
      loss of water, proteins, and plasma components from the organism. Due to its
      complex structure, the epidermal barrier with its major component, stratum
      corneum, is the rate-limiting unit for the penetration of exogenous substances
      through the skin. The epidermal barrier is not a static structure. The
      permeability barrier status can be modified by different external and internal
      factors such as climate, physical stressors, and a number of skin and systemic
      diseases. Today, different non-invasive approaches are used to monitor the skin
      barrier physical properties in vivo. The quantification of parameters such as
      transepidermal water loss, stratum corneum hydration, and skin surface acidity is
      essential for the integral evaluation of the epidermal barrier status. Novel
      methods such as in vivo confocal Raman microspectroscopy offer the possibility
      for precise and detailed characterization of the skin barrier. This paper will
      allow the readership to get acquainted with the non-invasive, in vivo methods for
      the investigation of the skin barrier.

PMID- 19118627
TI  - A freeze-dried formulation of bacteriophage encapsulated in biodegradable
      microspheres.
AB  - With the emergence of widespread antibiotic resistance, there has been renewed
      interest in the use of bacteriophages. While their potency, safety and
      specificity have underpinned their clinical potential, to date, little work has
      been focussed on their formulation with respect to controlled release and/or
      passive targeting. Here, we show that bacteriophages selective for Staphylococcus
      aureus or Pseudomonas aeruginosa can be encapsulated into biodegradable polyester
      microspheres via a modified w/o/w double emulsion-solvent extraction protocol
      with only a partial loss of lytic activity. Loss of lytic activity could be
      attributed to the exposure of the bacteriophages to the water-dichloromethane
      interface, with the lyophilization process itself having little effect. The
      microspheres were engineered to have an appropriate size and density to
      facilitate inhalation via a dry-powder inhaler and fluorescently labeled
      bacteriophages were distributed entirely within the internal porous matrix. The
      release profile showed a burst release phase (55-63% release within 30 min),
      followed by a sustained release till around 6h, as appropriate for pulmonary
      delivery. Despite the poor shelf-life of the formulation, the work is proof-of
      concept for the formulation and controlled delivery of bacteriophages, as
      suitable for the treatment of bacterial lung infections.

PMID- 19118628
TI  - Dopamine D3 receptor stimulation underlies the development of L-DOPA-induced
      dyskinesia in animal models of Parkinson's disease.
AB  - Development of L-DOPA-induced dyskinesia (LID) remains a major problem in the
      long-term treatment of Parkinson's disease (PD). Sensitization to L-DOPA
      correlates with ectopic expression of D3 dopamine receptors in the striatum,
      implicating D3 receptors in development of LID. We demonstrate that the selective
      D3 antagonist S33084 abolishes development of LID over 30 days in MPTP-lesioned
      marmosets without effecting the anti-parkinsonian actions of L-DOPA. Furthermore,
      following a 14 day washout, when challenged with L-DOPA in the absence of S33084,
      these animals continued to exhibit reduced LID. In the 6-OHDA-lesioned rat,
      S33084 similarly attenuated development of behavioural sensitization to L-DOPA.
      Additionally, L-DOPA-induced elevations in striatal pre-proenkephalin-A (PPE-A)
      (but not PPE-B, phospho[Thr(34)]DARPP-32, D1, and D2 receptor mRNA or D3 receptor
      levels) were reduced in S33084 treated animals. Our data suggest a role for D3
      receptors in the development of LID and suggest that initiating L-DOPA treatment
      with a D3 antagonist may reduce the development of LID in PD.

PMID- 19118629
TI  - Medial temporal lobe glutathione concentration in first episode psychosis: a 1H
      MRS investigation.
AB  - Glutathione (GSH) is implicated in the pathophysiology of schizophrenia. Previous
      brain spectroscopy studies, however, have been inconsistent, and there is little
      data available from first episode psychosis patients. This study compared brain
      GSH in a first episode cohort (n=30) to controls (n=18), using magnetic resonance
      spectroscopy (MRS), examining a temporal lobe voxel. Short-echo (TE 30 ms)
      acquisition proton MRS was performed on a 3T clinical magnetic resonance scanner.
      Comparison of the first-episode and control groups' GSH concentrations revealed a
      significant main effect of group (F(1,46)=4.7, p=0.035), but no main effect of
      hemisphere (F(1,46)=2.3, p=0.137) or group-by-side interactions (F(1,46)=0.4,
      p=0.513). Medial temporal lobe GSH concentrations in the first episode group were
      22% higher than those in the control group. This study provides further evidence
      of significant perturbations in brain GSH in first episode psychosis, and
      supports a broader involvement of GSH in the pathophysiology of schizophrenia.

PMID- 19118630
TI  - RGD-mediated adhesive interactions are important for peripheral axon outgrowth in
      vivo.
AB  - We identify an essential role for the RGD (Arg-Gly-Asp tripeptide) moiety in vivo
      during adult peripheral neuron regenerative growth. Beyond a peripheral nerve
      transection there were rises in the fibronectin extracellular matrix, and
      striking rises in the mRNA and protein expression of integrin subunits sensitive
      to RGD/fibronectin signalling. Neuron perikarya, axons and Schwann cells all
      expressed RGD/fibronectin sensitive integrins after injury. To evaluate the
      significance of RGD/fibronectin-integrin interactions, we infused solutions of a
      pentapeptide including the RGD motif (sRGD) serially and directly within the
      milieu of early axon growth across rat sciatic transection injuries. While low
      dose infusions of sRGD facilitated early axon ingrowth, we encountered inhibition
      of ingrowth and bridge formation with higher doses of sRGD indicating competitive
      disruption of RGD/fibronectin-integrin signalling. Fibronectin RGD moieties serve
      a critical and important role during peripheral axon outgrowth.

PMID- 19118631
TI  - Astrocyte-secreted GDNF and glutathione antioxidant system protect neurons
      against 6OHDA cytotoxicity.
AB  - In recent years, GDNF has emerged as a protective and restorative agent in
      several models of neurodegeneration; however, the exact molecular mechanisms
      responsible for these effects are not yet fully understood. Here we examined the
      effects of astrocytes secreting GDNF on neurons subjected to 6OHDA toxicity using
      in vitro neuron-astroglia co-cultures. Astrocytes were transduced with lentiviral
      vectors carrying the GDNF gene under the control of either human glial fibrillary
      acidic protein or cytomegalovirus promoters. The overexpression of GDNF,
      regardless of the promoter employed, had no obvious adverse effects on astroglia
      and the engineered cells stably produced and secreted GDNF for extended periods
      of time (> or =3 weeks). These astrocytes very effectively protected neurons
      against 6OHDA, in both mouse and human co-culture systems. The neuroprotective
      effects were mediated not only by GDNF, but also by the antioxidant GSH since its
      depletion reduced the level of GDNF protection. Furthermore, neurons and
      astrocytes expressed different components of GDNF signaling complex, suggesting
      that they might utilize separate pathways to mediate autocrine and paracrine
      effects of GDNF.

PMID- 19118634
TI  - Entomologically famous, evolutionarily unexplored: the first phylogeny of the
      lanternfly family Fulgoridae (Insecta: Hemiptera: Fulgoroidea).
AB  - Lanternflies (Insecta: Hemiptera: Fulgoridae) are frequently used as examples of
      unusual morphological evolution, with some species (such as the peanut-headed
      bug, Fulgora laternaria Linnaeus) also ubiquitously cited as icons of tropical
      insect biodiversity. Despite that entomological notoriety, the phylogeny of this
      charismatic planthopper family has never before been studied. Presented here are
      the results of a phylogenetic investigation of Fulgoridae based on DNA nucleotide
      sequence data from five genetic loci (18S rDNA, 28S rDNA, histone 3, wingless,
      and cytochrome oxidase I). The resulting topologies are used to test the higher
      classification of Fulgoridae, which is based primarily on characters associated
      with the curious head morphology of many included species. Analyses include a
      taxonomic sample of 69 fulgorid species representing 46 (of 110) genera, 10 (of
      11) tribes, and all 8 currently recognized subfamilies. Results of this study:
      (1) demonstrate the need for a revised classification of Fulgoridae, particularly
      at the higher taxonomic levels; (2) suggest that the genus Zanna is excluded from
      a monophyletic Fulgoridae; (3) indicate that there have been multiple losses of
      the extended head process across fulgorid evolution, with what appears to be
      convergence (in shape and/or loss) in distantly related lineages; and (4) suggest
      two alternative biogeographic hypotheses to explain the distribution of extant
      Fulgoridae, with either an Old World origin and a single subsequent colonization
      of the New World, or a contemporaneous diversification of Old and New World
      lineages.

PMID- 19118633
TI  - Characterization of cerebrovascular responses to hyperoxia and hypercapnia using
      MRI in rat.
AB  - Understanding cerebrovascular responses to hyperoxia and hypercapnia is important
      for investigating exogenous regulation of cerebral hemodynamics. We characterized
      gas-induced vascular changes in the brains of anesthetized healthy rats using
      magnetic resonance imaging (MRI) while the rats inhaled 100% O(2) (hyperoxia) and
      5% CO(2) (hypercapnia). We used echo planar imaging (EPI), arterial spin labeling
      (ASL), and intravascular superparamagnetic iron oxide nanoparticles (SPION) to
      quantify vascular responses as measured by blood oxygenation level dependence
      (BOLD), cerebral blood flow (CBF), cerebral blood volume (CBV), microvascular
      volume (MVV), and vessel size index (VSI) in multiple brain regions. Hyperoxia
      resulted in a statistically significant increase in BOLD-weighted MRI signal and
      significant decrease in CBF and CBV (P<0.05). During hypercapnia, we observed
      significant increases in BOLD signal, CBF, MVV, and CBV (P<0.05). Despite the
      regional variability, general trends of vasoconstriction and vasodilation were
      reflected in VSI changes during O(2) and CO(2) challenges. Interestingly, there
      was an evident spatial disparity between the O(2) and CO(2) stimuli-induced
      functional activation maps; that is, cortical and subcortical regions of the
      brain exhibited notable differences in response to the two gases. Hemodynamic
      parameters measured in the cortical regions showed greater reactivity to CO(2),
      whereas these same parameters measured in subcortical regions showed greater
      responsivity to O(2). Our results demonstrate significant changes of hemodynamic
      MRI parameters during systemic hypercapnia and hyperoxia in normal cerebral
      tissue. These gas-dependent changes are spatiotemporally distinctive, suggesting
      important feasibility for exogenously controlling local cerebral perfusion.

PMID- 19118632
TI  - Nanobody-aided structure determination of the EpsI:EpsJ pseudopilin heterodimer
      from Vibrio vulnificus.
AB  - Pseudopilins form the central pseudopilus of the sophisticated bacterial type 2
      secretion systems. The crystallization of the EpsI:EpsJ pseudopilin heterodimer
      from Vibrio vulnificus was greatly accelerated by the use of nanobodies, which
      are the smallest antigen-binding fragments derived from heavy-chain only camelid
      antibodies. Seven anti-EpsI:EpsJ nanobodies were generated and co-crystallization
      of EpsI:EpsJ nanobody complexes yielded several crystal forms very rapidly. In
      the structure solved, the nanobodies are arranged in planes throughout the
      crystal lattice, linking layers of EpsI:EpsJ heterodimers. The EpsI:EpsJ dimer
      observed confirms a right-handed architecture of the pseudopilus, but, compared
      to a previous structure of the EpsI:EpsJ heterodimer, EpsI differs 6 degrees in
      orientation with respect to EpsJ; one loop of EpsJ is shifted by approximately 5A
      due to interactions with the nanobody; and a second loop of EpsJ underwent a
      major change of 17A without contacts with the nanobody. Clearly, nanobodies
      accelerate dramatically the crystallization of recalcitrant protein complexes and
      can reveal conformational flexibility not observed before.

PMID- 19118635
TI  - Evolution underground: a molecular phylogenetic investigation of Australian
      burrowing freshwater crayfish (Decapoda: Parastacidae) with particular focus on
      Engaeus Erichson.
AB  - Phylogenetic relationships and species boundaries of Australian burrowing
      freshwater crayfish belonging to the genera Engaeus, Engaewa, Geocharax,
      Gramastacus and Tenuibranchiurus are investigated using combined mitochondrial
      and nuclear DNA sequence data and Bayesian and Maximum Parsimony methods.
      Phylogenies are statistically compared to previously published hypotheses.
      Engaeus, Engaewa, Geocharax, Gramastacus and Tenuibranchiurus form a strongly
      supported monophyletic clade. This grouping is independently supported by
      morphology but unites geographically highly disjunct lineages. Our data show two
      cryptic species in Geocharax, one cryptic species in Gramastacus and two cryptic
      species within the highly divergent Engaeus lyelli lineage. Using a Bayesian
      relaxed molecular clock method, the 16S rDNA data show generic-level
      diversification coinciding with the transition from a wet to arid palaeoclimate
      near the mid Miocene.

PMID- 19118637
TI  - Calcium transport in strongly calcifying laying birds: mechanisms and regulation.
AB  - Birds that lay long clutches (series of eggs laid sequentially before a "pause
      day"), among them the high-producing, strongly-calcifying Gallus gallus
      domesticus (domestic hen) and Coturnix coturnix japonica (Japanese quail),
      transfer about 10% of their total body calcium daily. They appear, therefore, to
      be the most efficient calcium-transporters among vertebrates. Such intensive
      transport imposes severe demands on ionic calcium (Ca2+) homeostasis, and
      activates at least two extremely effective mechanisms for Ca2+ transfer from food
      and bone to the eggshell. This review focuses on the development, action and
      regulation of the mechanisms associated with paracellular and transcellular Ca2+
      transport in the intestine and the eggshell gland (ESG); it also considers some
      of the proteins (calbindin, Ca2+ATPase, Na+/Ca2+ exchange, epithelial calcium
      channels (TRPVs), osteopontin and carbonic anhydrase (CA) associated with this
      phenomenon. Calbindins are discussed in some detail, as they appear to be a major
      component of the transcellular transport system, and as only they have been
      studied extensively in birds. The review aims to gather old and new knowledge,
      which could form a conceptual basis, albeit not a completely accepted one, for
      our understanding of the mechanisms associated with this phenomenon. In the
      intestine, the transcellular pathway appears to compensate for low Ca2+ intake,
      but in birds fed adequate calcium the major drive for calcium absorption remains
      the electrochemical potential difference (ECPD) that facilitates paracellular
      transport. However, the mechanisms involved in Ca2+ transport into the ESG lumen
      are not yet established. In the ESG, the presence of Ca2+-ATPase and calbindin-
      two components of the transcellular transport pathway--and the apparently uphill
      transport of Ca2+ support the idea that Ca2+ is transported via the transcellular
      pathway. However, the positive (plasma with respect to mucosa) electrical
      potential difference (EPD) in the ESG, among other findings, indicates that there
      may be major alternative or complementary paracellular passive transport
      pathways. The available evidence hints that the flow from the gut to the ESG,
      which occurs during a relatively short period (11 to 14 h out the 24- to 25.5-h
      egg cycle), is primarily driven by carbonic anhydrase (CA) activity in the ESG,
      which results in high HCO3(-) content that, in turn, "sucks out" Ca2+ from the
      intestinal lumen via the blood and ESG cells, and deposits it in the shell
      crystals. The increased CA activity appears to be dependent on energy input,
      whereas it seems most likely that the Ca2+ movement is secondary, that it
      utilizes passive paracellular routes that fluctuate in accordance with the
      appearance of the energy-dependent CA activity, and that the level of Ca2+
      movement mimics that of the CA activity. The on-off signals for the overall
      phenomenon have not yet been identified. They appear to be associated with the
      circadian cycle of gonadal hormones, coupled with the egg cycle: it is most
      likely that progesterone acts as the "off" signal, and that the "on" signal is
      provided by the combined effect of an as-yet undefined endocrine factor
      associated with ovulation and with the mechanical strain that results from "egg
      white" formation and "plumping". This strain may initially trigger the formation
      of the mammillae and the seeding of shell calcium crystals in the isthmus, and
      thereafter initiate the formation of the shell in the ESG.

PMID- 19118636
TI  - The resistance of electron-transport chain Fe-S clusters to oxidative damage
      during the reaction of peroxynitrite with mitochondrial complex II and rat-heart
      pericardium.
AB  - The effects of peroxynitrite and nitric oxide on the iron-sulfur clusters in
      complex II (succinate dehydrogenase) isolated from bovine heart have been studied
      primarily by EPR spectroscopy and no measurable damage to the constitutive 2Fe
      2S, 3Fe-4S, or 4Fe-4S clusters was observed. The enzyme can be repeatedly
      oxidized with a slight excess of peroxynitrite and then quantitatively re-reduced
      with succinate. When added in large excess, peroxynitrite reacted with at least
      one tyrosine in each subunit of complex II to form 3-nitrotyrosines, but activity
      was barely compromised. Examination of rat-heart pericardium subjected to
      conditions leading to peroxynitrite production showed a small inhibition of
      complex II (16%) and a greater inhibition of aconitase (77%). In addition,
      experiments performed with excesses of sodium citrate and sodium succinate on rat
      heart pericardium indicated that the "g approximately 2.01" EPR signal observed
      immediately following the beginning of conditions modeling oxidative/nitrosative
      stress, could be a consequence of both reversible oxidation of the constitutive
      3Fe-4S cluster in complex II and degradation of the 4Fe-4S cluster in aconitase.
      However, the net signal envelope, which becomes apparent in less than 1min
      following the start of oxidative/nitrosative conditions, is dominated by the
      component arising from complex II. Taking into account the findings of a previous
      study concerning complexes I and III (L.L. Pearce, A.J. Kanai, M.W. Epperly, J.
      Peterson, Nitrosative stress results in irreversible inhibition of purified
      mitochondrial complexes I and III without modification of cofactors, Nitric Oxide
      13 (2005) 254-263) it is now apparent that, with the exception of the cofactor in
      aconitase, mammalian (mitochondrial) iron-sulfur clusters are surprisingly
      resistant to degradation stemming from oxidative/nitrosative stress.

PMID- 19118638
TI  - On the role of Cdc2 kinase during meiotic maturation of oocyte in the Chinese
      mitten crab, Eriocheir sinensis.
AB  - Cdc2 kinase is a catalytic subunit of maturation-promoting factor (MPF), a
      central factor for inducing the meiotic maturation of oocyte. To understand the
      role of Cdc2 kinase on the oocyte maturation in crustacean, a complete cDNA
      sequence of Cdc2 kinase was cloned from Chinese mitten crab Eriocheir sinensis
      and its spatial-temporal expression profiles were analyzed during oogenesis at
      RNA and protein levels. The crab Cdc2 cDNA (1364 bp) encodes for a 299 amino
      acids protein with calculated molecular weight of 34.7 kDa. The Cdc2 mRNAs level
      showed no significant change in the ovary during oogenesis, whereas higher
      protein level was found at previtellogenesis, late vitellogenesis and germinal
      vesicle breakdown (GVBD) stages. Two forms (35 kDa and 34 kDa) of Cdc2 proteins
      were simultaneously identified in ovary at all stages. Immunocytochemistry
      analysis revealed that Cdc2 proteins locate exclusively in ooplasm of
      previtellogenic oocyte, and then relocate into germinal vesicle at vitellogenesis
      stage and accumulate on meiotic spindle at oocyte maturation. These findings
      suggest that Cdc2 kinase has essential roles in inducing GVBD and generating
      meiotic apparatus during the crab oocyte maturation.

PMID- 19118639
TI  - Compartmentalization of proteins in lipid droplet biogenesis.
AB  - Our existing understanding of the structure, protein organization and biogenesis
      of the lipid droplet has relied heavily on microscopical techniques that lack
      resolution and the ability to preserve native cellular and protein composition.
      The electron microscopic technique of freeze-fracture replica immunogold labeling
      (FRIL) overcomes these problems, and is currently providing new perspectives in
      the field. Because of the property of frozen lipids to deflect the fracture
      plane, en face views of the lipid droplet and its component layers are revealed
      for high resolution visualization. By means of immunogold labeling, proteins
      involved in the accretion and mobilization of lipids, notably the PAT family
      proteins, can be localized at and in the droplet. Application of this approach
      demonstrates that, contrary to prevailing wisdom, the PAT family proteins are not
      invariably restricted to the surface of the lipid droplet but can occur
      throughout the core. The notion that lipid droplet biogenesis involves neutral
      lipid accumulation within the ER membrane bilayer followed by budding off,
      enclosed by a protein-containing phospholipid monolayer, is not substantiated.
      Instead, lipid droplets appear to develop externally to both ER membranes at
      specialized sites in which the ER enwraps the droplet, and the facing leaflets of
      the ER membrane and droplet surface are enriched in adipophilin. PAT family
      proteins are not, as often stated, specific to the lipid droplet, but are widely
      present in the plasma membrane where, under conditions of lipid loading, they
      adopt a similar configuration to that of specialized sites in the ER. FRIL has
      further provided new insights into the mechanism of secretion of a special type
      of lipid droplet, the milk fat globule. These examples highlight the contribution
      of the FRIL technique to critical appraisal and development of concepts in the
      lipid droplet field.

PMID- 19118640
TI  - Knowledge of, perceptions of, and attitudes toward epilepsy among university
      students in Kuwait.
AB  - The aim of this study was to explore, using a self-administered questionnaire,
      university students' knowledge of, perceptions of, and attitudes toward epilepsy.
      Approximately 1.7% considered epilepsy a contagious disease, and 10.5%, a form of
      insanity. About 25 and 34% of students thought that epilepsy is caused by an evil
      spirit and the evil eye, respectively, and 17.4% thought epilepsy is punishment
      from God. About 8% believed patients with epilepsy should not marry, and 12.5%
      thought they should not have children. Similarly, 11.7% thought patients with
      epilepsy cannot think or judge like people without epilepsy, and 26.2% would not
      employ someone with epilepsy in a clerical job. Approximately 56% objected to
      marrying someone with epilepsy, and 12.5% would not allow their child to play
      with a child with epilepsy. In conclusion, university students in Kuwait have a
      vague knowledge of the causes of epilepsy. Misconceptions about and negative
      attitudes toward epilepsy are unexpectedly high among these university students.

PMID- 19118641
TI  - Prospective study of long-term results and prognostic factors after conservative
      surgery for small bowel Crohn's disease.
AB  - BACKGROUND & AIMS: Several bowel-sparing techniques have been proposed for
      treating patients with CD, but there have been no prospective studies analyzing
      risk factors and long-term outcome. We prospectively evaluated safety and long
      term efficacy of conservative surgery for patients with complicated CD. METHODS:
      From 1993-2007, 393 of 502 consecutive patients underwent surgery for complicated
      CD of the small bowel. Those with colonic involvement were excluded. The Student
      t test, chi(2) test, Kaplan-Meier estimates, and Cox proportional hazard model
      were used to analyze postoperative complications and long-term outcome. RESULTS:
      A total of 865 jejunoileal segments underwent 318 small bowel resections and 367
      strictureplasties (either classic or nonconventional). There were no deaths; the
      complication rate was 5.6%, and the cumulative 10-year recurrence rate was 35%.
      None of the prognostic factors were correlated with postoperative complications.
      Younger age, an upper jejunoileal location, stricturing behavior, and small-bowel
      wall thickening 12 months after surgery showed hazard ratios of 2.4 (95%
      confidence interval [CI], 1-5.4; P = .03), 2.5 (95% CI, 1.3-4.7; P = .004), 2.2
      (95% CI, 1.1-4.1; P = .01), and 4.5 (95% CI, 2.3-8.6; P = .000), respectively.
      Immunomodulator therapy failed to reduce long-term surgical recurrence.
      CONCLUSIONS: Young patients with extended and stricturing disease are at high
      risk for disease recurrence after surgery. Bowel wall thickening was a reliable
      prognostic factor for these patients. Conservative surgery is safe and effective
      in treating patients with jejunoileal CD and should be considered as the first
      line surgical treatment, preventing the risk of short bowel syndrome caused by
      repeated resections.

PMID- 19118642
TI  - A case-control study of sociodemographic and geographic characteristics of 335
      children with eosinophilic esophagitis.
AB  - BACKGROUND & AIMS: The epidemiology of pediatric eosinophilic esophagitis (EE) is
      poorly characterized. In this study, we aimed to determine demographic,
      socioeconomic, and geographic characteristics of our cohort of EE children.
      METHODS: A case-control design was used to compare 335 EE subjects with control
      subjects from gastroenterology (GI) and allergy clinics as well as 2000 U.S.
      census data. RESULTS: EE subjects were significantly different than the greater
      Philadelphia population as well as control subjects from our gastroenterology and
      allergy clinics. EE subjects were 83.6% Caucasian, compared with 70.9% of GI
      control subjects (odds ratio [OR], 2.17; P < .001; confidence interval [CI], 1.52
      3.11), 64.9% of allergy control subjects (OR, 2.83; P < .001; CI, 1.99-4.04), and
      73.0% of the greater Philadelphia population. EE subjects were 75.8% male,
      compared with 48.0% of GI control subjects (OR, 3.39; P < .001; CI, 2.47-4.65),
      60.4% of allergy control subjects (OR, 1.62; P < .001; CI, 1.19-2.19), and 48.0%
      of the greater Philadelphia population. We initially demonstrated that EE
      subjects are more affluent, more educated, and reside more often in suburban
      areas. However, Caucasian race was a significant confounding variable and
      accounted for socioeconomic or geographic differences among EE subjects and our
      control populations with one exception. A significant difference remained between
      suburban and urban residence in EE and allergy control populations. CONCLUSIONS:
      EE subjects are significantly different than control groups in their demographic
      characteristics of Caucasian race and male sex. EE subject socioeconomic and
      geographic characteristics are not different than our typical referral patterns
      to GI clinic when adjusted for race as a confounding factor.

PMID- 19118643
TI  - Integration of racial, cultural, ethnic, and socioeconomic factors into a
      gastrointestinal pathophysiology course.
AB  - BACKGROUND & AIMS: Our study describes a faculty development program to encourage
      the integration of racial, cultural, ethnic, and socioeconomic factors such as
      obesity, inability to pay for essential medications, the use of alternative
      medicine, dietary preferences, and alcoholism in a gastrointestinal
      pathophysiology course. METHODS: We designed a 1-hour faculty development session
      with longitudinal reinforcement of concepts. The session focused on showing the
      relevance of racial, ethnic, cultural, and socioeconomic factors to
      gastrointestinal diseases, and encouraged tutors to take an active and pivotal
      role in discussion of these factors. The study outcome was student responses to
      course evaluation questions concerning the teaching of cultural and ethnic issues
      in the course as a whole and by individual tutorials in 2004 (pre-faculty
      development) and in 2006 to 2008 (post-faculty development). RESULTS: Between
      2004 and 2008, the proportion of students reporting that "Issues of culture and
      ethnicity as they affect topics in this course were addressed" increased
      significantly (P = .000). From 2006 to 2008, compared with 2004, there was a
      significant increase in the number of tutors who "frequently" taught culturally
      competent care according to 60% or greater of their tutorial students (P = .003).
      The tutor's age, gender, prior tutor experience, rank, and specialty did not
      significantly impact results. CONCLUSIONS: An innovative faculty development
      session that encourages tutors to discuss racial, cultural, ethnic, and
      socioeconomic issues relevant to both care of the whole patient and to the
      pathophysiology of illness is both effective and applicable to other preclinical
      and clinical courses.

PMID- 19118644
TI  - Noninvasive assessment of hepatic steatosis.
AB  - Hepatic steatosis, the accumulation of lipids within hepatocytes, is a common
      condition. The prevalence of its most frequent manifestation, nonalcoholic fatty
      liver disease (NAFLD), has been estimated to be as high as 35% in some
      populations. Currently, liver biopsy is the gold standard for the diagnosis and
      assessment of severity of hepatic steatosis, staging of fibrosis, and is the only
      modality able to differentiate bland steatosis from steatohepatitis. However, its
      invasiveness, significant side effect profile, and susceptibility to sampling
      error ultimately make it a suboptimal tool. Accordingly, focus has been placed on
      noninvasive radiologic techniques for hepatic fat detection and quantification.
      The rationale, performance characteristics, and limitations of traditional
      noninvasive measures, including ultrasound, computed tomography, and magnetic
      resonance (MR) spectroscopy and imaging, are reviewed. A novel MR method, the
      spectrally modeled relaxation-invariant technique, overcomes the inherent
      weaknesses of conventional MR to diagnose and quantify hepatic steatosis over its
      entire range of severity. Noninvasive radiologic techniques, particularly MR, can
      be applied broadly, including in the diagnosis of NAFLD in asymptomatic patients
      with elevated serum aminotransferase levels, longitudinal monitoring of disease
      progression or response to treatment, population-based epidemiologic or
      observational studies, and drug discovery.

PMID- 19118645
TI  - VITO-2, a new SID domain protein, is expressed in the myogenic lineage during
      early mouse embryonic development.
AB  - MCAT elements and its cognate binding partners, the transcription enhancer
      factors (TEFs) play important roles in the regulation of expression of several
      muscle-specific genes. The biological effects of TEFs strongly depend on
      different co-factors, which might act as co-activators or anti-repressors to
      enable transcriptional activation of target genes by TEFs. Previously, we have
      cloned and characterized VITO-1, which acts as a skeletal muscle-specific
      transcriptional co-activator of TEFs. Here we describe the cloning and expression
      profile of a related gene, VITO-2 (also termed Vgl-3), which shares a high
      homology with VITO-1 in the SID domain responsible for interaction with TEFs.
      During early embryonic and fetal development VITO-2 is mainly expressed in the
      myogenic lineage with an onset of expression in the myotomes of somites VI at
      E9.5 slightly later than VITO-1. At later developmental stages VITO-2 is
      predominantly found in the nervous system. In adult mice VITO-2 was detected in
      different tissues, including skeletal muscle, heart, kidney, liver and brain,
      where it was found in cortical and cerebellar neurons as well as in Purkinje
      cells. The expression of VITO-2 in the mesoderm was repressed by the notch/delta
      pathway and activated by Myf-5 since Dll-1 mutant showed an aberrant expression
      of VITO-2 but not VITO-1 in the tail bud and in the caudal neural tube at E10.5
      while Myf-5 mutant mice lack expression of VITO-1 and VITO-2 in somites until
      E10.5.

PMID- 19118646
TI  - Evolutionary biology, community ecology and avian influenza research.
AB  - The epidemiology of H5N1 HPAI is still unclear despite the efforts of the
      research community. Studies bringing new insights add more variability in the
      host-pathogen system and uncertainty in the prediction of local risks. Global
      analyses of the pathways of wild birds in parallel with virus outbreaks have
      brought limited conclusions once the raw information was extracted from relevant
      maps. In this article, we propose an integration of epidemiology, evolutionary
      biology and community ecology on a local level in a research framework. This
      multidisciplinary approach aims at understanding the pathogen transmission
      processes at the interface between different bird groups whether wild or
      domesticated. We believe that this ecological data brought together with the
      epidemiological and molecular data is a key element to explore the mechanism of
      the AIV ecology in their hosts.

PMID- 19118648
TI  - Inducible nitric oxide synthase inhibition attenuates lung tissue responsiveness
      and remodeling in a model of chronic pulmonary inflammation in guinea pigs.
AB  - We evaluated the influence of iNOS-derived NO on the mechanics, inflammatory, and
      remodeling process in peripheral lung parenchyma of guinea pigs with chronic
      pulmonary allergic inflammation. Animals treated or not with 1400 W were
      submitted to seven exposures of ovalbumin in increasing doses. Seventy-two hours
      after the 7th inhalation, lung strips were suspended in a Krebs organ bath, and
      tissue resistance and elastance measured at baseline and after ovalbumin
      challenge. The strips were submitted to histopathological measurements. The
      ovalbumin-exposed animals showed increased maximal responses of resistance and
      elastance (p<0.05), eosinophils counting (p<0.001), iNOS-positive cells
      (p<0.001), collagen and elastic fiber deposition (p<0.05), actin density (p<0.05)
      and 8-iso-PGF2alpha expression (p<0.001) in alveolar septa compared to saline
      exposed ones. Ovalbumin-exposed animals treated with 1400 W had a significant
      reduction in lung functional and histopathological findings (p<0.05). We showed
      that iNOS-specific inhibition attenuates lung parenchyma constriction,
      inflammation, and remodeling, suggesting NO-participation in the modulation of
      the oxidative stress pathway.

PMID- 19118649
TI  - Rapid elevation of Inos and decreases in abundance of other proteins at pupal
      diapause termination in the flesh fly Sarcophaga crassipalpis.
AB  - We analyzed changes in brain proteins 24 h after pupal diapause termination in
      Sarcophaga crassipalpis by a combination of 2-dimensional gel electrophoresis and
      mass spectrometry. The proteome analysis revealed significant changes in 20
      proteins, 11 of which represented >or=2.5-fold changes. Three proteins were
      present only in the brains of diapausing pupae. Among the most abundant proteins
      that showed a change, 1 was more abundant, 7 were less abundant, and 2 were
      absent following diapause termination. The protein that increased in abundance
      following diapause termination showed highest identity to myo-inositol-1
      phosphate synthase (Inos). Proteins that decreased at diapause termination
      included those showing highest identities to fatty acid binding protein, CG2331
      PA, twinstar, catalase, and a histone. Proteins absent at diapause termination
      included ribosomal protein L17A and one unnamed protein. An increase of Inos
      protein level was confirmed using Western blot analysis. Attempts to terminate
      diapause by injection of several Inos-related metabolites failed, thus suggesting
      that the elevation of Inos at diapause termination is downstream of the
      physiological regulation that initiates development.

PMID- 19118650
TI  - Transition of haemoglobin between two tertiary conformations: Inositol
      hexakisphosphate increases the transition constant and the affinity of sheep
      haemoglobin for 5,5'-dithiobis(2-nitrobenzoate).
AB  - The equilibrium constant (K(equ)) for the reaction of 5,5'-dithiobis(2
      nitrobenzoate) - DTNB - with the CysF9[93]beta sulphydryl group of the
      haemoglobins of the sheep decreases by about two orders of magnitude between pH
      approximately 5.6 and 9.2: from a mean of 7.2+/-1 to a mean of 0.044+/-0.01.
      Calculations from the pH dependence of K(equ) show that in the r-t tertiary
      conformational transition of haemoglobin the t isomer population is 50.7 and
      61.8% for the major and minor haemoglobins, respectively. In the presence of
      inositol hexakisphosphate (inositol-P(6)), K(equ) increases for both haemoglobins
      by about an order of magnitude through most of the pH range. The t isomer
      population also increases to 82.1 and 79.6% for the major and minor haemoglobins,
      respectively. These results indicate that inositol-P(6) increases the affinity of
      the sulphydryl for DTNB by increasing the population of the t isomer. It is
      highly probable that a minimum four-state model that includes the r-t transition
      is required for a full understanding of haemoglobin function.

PMID- 19118647
TI  - Role of chemoreceptors in mediating dyspnea.
AB  - Dyspnea, or the uncomfortable awareness of respiratory distress, is a common
      symptom experienced by most people at some point during their lifetime. It is
      commonly encountered in individuals with pulmonary disease, such as chronic
      obstructive pulmonary disease (COPD), but can also be seen in healthy individuals
      after strenuous exercise, at altitude or in response to psychological stress.
      Dyspnea is a multifactorial sensation involving the brainstem, cortex, and limbic
      system, as well as mechanoreceptors, irritant receptors and chemoreceptors.
      Chemoreceptors appear to contribute to the sensation of dyspnea in two ways. They
      stimulate the respiratory control system in response to hypoxia and/or
      hypercapnia, and the resultant increase respiratory motor output can be
      consciously perceived as unpleasant. They also can induce the sensation of
      dyspnea through an as yet undetermined mechanism-potentially via direct ascending
      connections to the limbic system and cortex. The goal of this article is to
      briefly review how changes in blood gases reach conscious awareness and how
      chemoreceptors are involved in dyspnea.

PMID- 19118651
TI  - Differential proteomic analysis of soluble extracellular proteins reveals the
      cysteine protease and cystatin involved in suspension-cultured cell proliferation
      in rice.
AB  - Extracellular matrix proteins play crucial roles in plant development,
      morphogenesis, cell division, and proliferation. To identify extracellular
      proteins that regulate cell growth, the soluble proteins of extracellular matrix
      were extracted from suspension-cultured rice cells for different lengths of time.
      The extract obtained from 3-d cultures was found to increase cells' fresh weight,
      while extracts from 6-d and 9-d cultures showed no effect on cells' growth. A
      comparative proteomic analysis was used to identify soluble extracellular
      proteins differentially expressed between 3 and 6 days in suspension-cultured
      cells. Ten unique protein spots were isolated and identified by mass
      spectrometry. Among them, included a cysteine protease (OsCP) and a putative
      cysteine protease inhibitor (cystatin, OC-I). OsCP has been down regulated in
      vivo using RNAi transgenic lines. The fresh and dry weight growth rates of OsCP
      RNAi cell lines were lower than empty vector control. Recombinant protein of OC-I
      could inhibit the OsCP protease activity, also it could inhibit the weight
      increase of suspension-culture cell as well as extracellular protease activity.
      These results suggest that OsCP and OC-I may be involved in the process of
      suspension-cultured rice cells proliferation.

PMID- 19118652
TI  - Molecular determinants of substrate and inhibitor specificities of the
      Penicillium griseofulvum family 11 xylanases.
AB  - Penicillium griseofulvum possesses two endo-(1,4)-beta-xylanase genes, PgXynA and
      PgXynB, belonging to family 11 glycoside hydrolases. The enzymes share 69%
      identity, a similar hydrolysis profile i.e. the predominant production of
      xylobiose and xylotriose as end products from wheat arabinoxylan and a
      specificity region of six potential xylose subsites, but differ in terms of
      catalytic efficiency which can be explained by subtle structural differences in
      the positioning of xylohexaose in the PgXynB model. Site-directed mutagenesis of
      the "thumb" region revealed structural basis of PgXynB substrate and inhibitor
      specificities. We produced variants displaying increased catalytic efficiency
      towards wheat arabinoxylan and xylo-oligosaccharides and identified specific
      determinants in PgXynB "thumb" region responsible for resistance to the wheat
      xylanase inhibitor XIP-I. Based on kinetic analysis and homology modeling, we
      suggested that Pro130(PgXynB), Lys131(PgXynB) and Lys132(PgXynB) hamper
      flexibility of the loop forming the "thumb" and interfere by steric hindrance
      with the inhibitor.

PMID- 19118653
TI  - Redox properties and crystal structures of a Desulfovibrio vulgaris flavodoxin
      mutant in the monomeric and homodimeric forms.
AB  - The mutant S64C of the short-chain flavodoxin from Desulfovibrio vulgaris has
      been designed to introduce an accessible and reactive group on the protein
      surface. Crystals have been obtained of both the monomeric and homodimeric forms
      of the protein, with the cofactor FMN in either the oxidized or the one electron
      reduced (semiquinone) state, and the structures have been determined to high
      resolution. The redox properties of the different species have been investigated
      and the variations observed with respect to wild type have been related to the
      structural changes induced by the mutation and S-S bridge formation.

PMID- 19118654
TI  - Barley seed proteomics from spots to structures.
AB  - Barley is a major cereal crop grown mainly for feed and malting. Two-dimensional
      gel electrophoresis has been used to analyse barley proteins for over 20 years
      and more recently, mass spectrometry was applied. In the absence of a genome
      sequence, barley gene and EST sequences combined with information from rice and
      other cereals facilitate identification of barley proteins. Several hundred
      barley seed proteins are identified and lower abundance proteins including
      membrane proteins are now being analysed. In the present review we focus on
      variation in protein profiles of seed tissues during grain filling, maturation,
      germination and radicle elongation. Cultivar comparisons and genetic mapping of
      polymorphic protein spots in doubled haploid populations provide a means to link
      the genome to the proteome and identify proteins that can influence grain
      quality. Many proteins appear in multiple forms on 2D-gels. Specific protein
      families, including peroxidases and alpha-amylases have been subjected to in
      depth analysis resulting in characterisation of different isozymes, post
      translational modifications and processing. A functional proteomics study
      focusing on the seed thioredoxin system has led to identification of thioredoxin
      target proteins, quantitative analysis of reduction of individual target
      disulphides and structural studies to gain insight into determinants for target
      protein recognition by thioredoxin.

PMID- 19118655
TI  - Comparative proteomics analysis of caspase-9-protein complexes in untreated and
      cytochrome c/dATP stimulated lysates of NSCLC cells.
AB  - Apoptosis is a process of cellular suicide executed by caspases. Impaired
      activation of caspase-9 may contribute to chemoresistance in cancer. Activation
      of caspase-9 occurs after binding to Apaf-1 and formation of the apoptosome in
      the presence of cytochrome c/(d)ATP. We used a proteomics approach to identify
      proteins in caspase-9-protein complexes in extracts derived from NSCLC cells
      with(out) cytochrome c/dATP. Using co-immunoprecipitation, one-dimensional gel
      electrophoresis and tandem mass spectrometry, 38 proteins were identified of
      which 24 differential interactors. The differential interactors can be
      functionally assigned to cytoskeletal (re)organization and cell motility,
      catalytic activity, and transcriptional processes and apoptosis. The interaction
      of caspase-9 with Apaf-1 was confirmed and acetylserotonin-O-methyltransferase
      like protein was identified as a candidate substrate of caspase-9. Novel
      interactors were found including galectin-3, swiprosin-1 and the membrane
      cytoskeleton linkers Ezrin/Radixin/Moesin. Co-immunoprecipitation and Western
      blot experiments confirmed the interaction of caspase-9 with several identified
      binding partners. A large number of cytoskeletal proteins associated with
      unprocessed caspase-9 may indicate a scaffold function of this structure and/or
      may act as caspase substrates during apoptosis. Together, our results indicate
      that proteomic analysis of the caspase-9-associated protein complexes is a
      powerful exploratory approach to identify novel caspase substrates and/or
      regulators of caspase-9-dependent apoptosis.

PMID- 19118656
TI  - Sites of 18S rRNA contacting mRNA 3' and 5' of the P site codon in human
      ribosome: a cross-linking study with mRNAs carrying 4-thiouridines at specific
      positions.
AB  - Long synthetic mRNAs were used to study the positioning of the E site codon, the
      2nd and 3rd nucleotides of the A site bound codon and a nucleotide 3' of this
      codon with respect to the 18S rRNA in the human 80S ribosome. The mRNAs contained
      a GAC triplet coding for Asp and a single 4-thiouridine residue (s(4)U) upstream
      or downstream of the GAC codon. In the presence of tRNA(Asp), the GAC codon of
      the mRNAs was targeted to the ribosomal P site thus placing s(4)U in one of the
      following positions -3, -2, -1, +5, +6 or +7 with respect to the first nucleotide
      of the P site bound codon. It was found that mRNAs that bore s(4)U in positions
      +5 to +7 cross-linked to the 18S rRNA nucleotides C1696, C1698 and 1820-1825, the
      distribution of cross-links among these targets depending on the position of
      s(4)U. Cross-links of mRNAs containing s(4)U in positions -3 to -1 were found in
      the region 1699-1704 of the 18S rRNA. In the absence of tRNA, all mRNAs cross
      linked only to C1696 and C1698. Absence of the cross-linked nucleotides C1696 and
      C1698 in the case of mRNAs containing s(4)U in positions -3 to -1 confirmed that
      tRNA(Asp) actually phased the mRNA on the ribosome.

PMID- 19118657
TI  - Involvement of Oct-1 in the regulation of CDKN1A in response to clinically
      relevant doses of ionizing radiation.
AB  - CDKN1A is a cyclin-dependent kinase inhibitor that plays a critical role in cell
      cycle checkpoint regulation. It is transcriptionally induced by TP53 (p53)
      following exposure to ionizing radiation (IR). Induction of CDKN1A after
      irradiation is closely related to IR-sensitivity of tumor cells, but the
      underlying mechanisms remain obscure because conventional reporter gene systems
      respond poorly to IR unless hyperlethal doses are used. Here, we performed a
      promoter analysis of the CDKN1A gene following irradiation with clinically
      relevant doses of IR using the adeno-associated virus-mediated reporter system
      which we have recently shown to be highly responsive to IR. We demonstrate that
      there are regulatory elements at -1.1 kb, -1.4 kb, and -1.8 kb, and deletion of
      these elements attenuate induction of the CDKN1A gene promoter in response to 0.2
      2.0 Gy of IR. EMSA and ChIP assays showed that Oct-1 binds constitutively to the
      elements at -1.1 kb and -1.8 kb. Functional involvement of Oct-1 was confirmed by
      RNA interference targeting the Oct-1 gene, which suppressed both the basal and IR
      inducible components of the CDKN1A expression. Thus, our results reveal that Oct
      1 is crucial to the TP53-mediated regulation of the CDKN1A gene promoter
      following exposure to clinically relevant doses of IR.

PMID- 19118658
TI  - Green tea polyphenols mitigate deterioration of bone microarchitecture in middle
      aged female rats.
AB  - Our previous study demonstrated that green tea polyphenols (GTP) benefit bone
      health in middle-aged female rats without (sham, SH) and with ovariectomy (OVX),
      because of GTP's antioxidant capacity. The current study further evaluates
      whether GTP can restore bone micro-structure in both gonad-intact and gonadal
      hormone-deficient middle-aged female rats. A 16-week study was performed based on
      a 2 (SH vs. OVX)x3 (no GTP, 0.1% GTP, and 0.5% GTP in drinking water) factorial
      design using 14-month-old female rats (n=10/group). An additional 10 rats were
      euthanized at the beginning of study to provide baseline parameters. Analysis
      using dual-energy X-ray absorptiometry, histomorphometry, and micro-computed
      tomography showed that GTP supplementation resulted in (a) increased trabecular
      volume, thickness, number, and bone formation of proximal tibia, periosteal bone
      formation rate of tibia shaft, and cortical thickness and area of femur, and (b)
      decreased trabecular separation and bone erosion of proximal tibia, and
      endocortical bone eroded surface of tibia shaft. We concluded that drinking water
      supplemented with GTP mitigated deterioration of bone microarchitecture in both
      intact and ovariectomized middle-aged female rats by suppressing bone erosion,
      enhancing bone formation, and modulating endocortical and cancellous bone
      compartments, resulting in a larger net bone volume.

PMID- 19118659
TI  - Tibial geometry in individuals with neurofibromatosis type 1 without
      anterolateral bowing of the lower leg using peripheral quantitative computed
      tomography.
AB  - INTRODUCTION: Lower leg bowing with tibial pseudarthrosis is associated with
      neurofibromatosis type 1 (NF1). The objective of the study is to determine if the
      geometry of the lower limb in individuals with neurofibromatosis type 1 (NF1)
      differs from controls, and to characterize the osseous components of the tibia in
      NF1. METHODS: Peripheral quantitative computed tomography (pQCT) of the lower
      limb was performed (90 individuals with NF1 without tibial and/or fibular
      dysplasia: 474 healthy individuals without NF1). Subjects were 4-18 years of age.
      Individuals with NF1 were compared to controls using an analysis-of-covariance
      with a fixed set of covariates (age, weight, height, Tanner stage, and gender).
      RESULTS: Using pQCT, NF1 individuals without bowing of the lower leg have smaller
      periosteal circumferences (p<0.0001), smaller cortical area (p<0.0001), and
      decreased tibial cortical and trabecular bone mineral content (BMC) (p<0.0001)
      compared to controls. DISCUSSION: Individuals with NF1 have a different geometry
      of the lower leg compared to healthy controls suggesting that NF1
      haploinsufficiency impacts bone homeostasis although not resulting in overt
      anterolateral bowing of the lower leg.

PMID- 19118660
TI  - Overexpression of cathepsin K accelerates the resorption cycle and osteoblast
      differentiation in vitro.
AB  - Bone resorption is a multistep process including osteoclast attachment,
      cytoskeletal reorganization, formation of four distinct plasma membrane domains,
      and matrix demineralization and degradation followed by cell detachment. The
      present study describes the intracellular mechanisms by which overexpression of
      cathepsin K in osteoclasts results in enhanced bone resorption. Osteoclasts and
      bone marrow-derived osteoclast and osteoblast precursors were isolated from mice
      homozygous (UTU17(+/+)) and negative for the transgene locus. Cells cultured on
      bovine cortical bone slices were analyzed by fluorescence and confocal laser
      scanning microscopy, and bone resorption was studied by measurements of
      biochemical resorption markers, morphometry, and FESEM. Excessive cathepsin K
      protein and enzyme activity were microscopically observed in various
      intracellular vesicles and in the resorption lacunae of cathepsin K
      overexpressing osteoclasts. The number of cathepsin K-containing vesicles in
      UTU17(+/+) osteoclasts was highly increased, and co-localization with markers for
      the biosynthetic and transcytotic pathways was observed throughout the cytoplasm.
      As a functional consequence of cathepsin K overexpression, biochemical resorption
      markers were increased in culture media of UTU17(+/+) osteoclasts. Detailed
      morphometrical analysis of the erosion in bone slices indicated that the
      increased biosynthesis of cathepsin K was sufficient to accelerate the
      osteoclastic bone resorption cycle. Cathepsin K overexpression also enhanced
      osteogenesis and induced the formation of exceptionally small, actively resorbing
      osteoclasts from their bone marrow precursors in vitro. The present study
      describes for the first time how enhancement in one phase of the osteoclastic
      resorption cycle also stimulates its other phases and further demonstrate that
      tight control and temporal coupling of mesenchymal and hematopoietic bone cells
      in this multistep process.

PMID- 19118661
TI  - Sex determination and sexual development. Preface.

PMID- 19118662
TI  - Somatic sexual differentiation in Caenorhabditis elegans.
AB  - The two sexes of the nematode Caenorhabditis elegans are the self-fertile
      hermaphrodite (essentially a female with a mixed germ line) and the male, and
      these differ extensively in anatomy, physiology, and behavior. At hatching, C.
      elegans larvae of each sex are nearly indistinguishable, differing mainly in the
      sex-specific death of a handful of neurons. After birth, however, a number of
      blast cells undergo radically different lineages and differentiation programs in
      the two sexes, leading to adults in which about one-third of cells are overtly
      dimorphic. The first C. elegans mutants causing discordance between genetic and
      phenotypic sex were isolated more than 30 years ago. Since then much progress has
      been made in uncovering the chromosomal elements and downstream regulatory
      pathways that control sex determination and sexual differentiation in the worm.
      The primary signal for sex determination is the ratio of X chromosomes to sets of
      autosomes, with hermaphrodites normally having two X chromosomes (XX) and males
      one (XO). The X:A signal is exquisitely dose-sensitive and operates via a group
      of X-linked regulators acting in opposition to a group of autosomal regulators
      that compete for the control of the master sex regulator xol-1. The activity of
      xol-1 coordinately regulates the formation of an active X chromosome dosage
      compensation complex and the activity of a sex determination regulatory cascade.
      The sex determination pathway globally controls all sexually dimorphic features
      by conferring sex specificity on downstream regulatory modules, largely via the
      action of TRA-1, a Ci/GLI family transcription factor with high activity in
      hermaphrodites and low activity in males. Much of this regulation involves the
      imposition of sex-specific activity on general developmental regulators in
      specific cell lineages. Recent work has answered long-standing questions about
      the molecular mechanisms controlling the sex determination pathway and shown that
      some C. elegans sexual regulators have counterparts regulating sexual development
      in other phyla.

PMID- 19118663
TI  - Sex determination in the Caenorhabditis elegans germ line.
AB  - Sexual identity is one of the most important factors that determine how an animal
      will develop. Although it controls many dimorphic tissues in the body, its most
      ancient role is in the germ line, where it species that some cells become sperm,
      and others become eggs. In most animals, these two fates occur in distinct sexes.
      However, certain nematodes like C. elegans produce XX hermaphrodites, which make
      both types of gametes. In these animals, a core sex-determination pathway
      regulates the development of both the body and the germ line. However, modifier
      genes alter the activity of this pathway in germ cells, and these changes are
      critical for allowing XX animals to produce oocytes and sperm in an otherwise
      female body. In this review, I focus on (1) the core sex-determination pathway,
      (2) the activity of the transcription factor TRA-1 and its immediate targets fog
      1 and fog-3 in germ cells, (3) how the regulation of tra-2 activity allows XX
      spermatogenesis, and (4) how the regulation of fem-3 activity maintains the
      appropriate balance between TRA-2 and FEM-3 in the germ line. Finally, I consider
      the major questions in this field that are driving new research.

PMID- 19118664
TI  - The creation of sexual dimorphism in the Drosophila soma.
AB  - Animals have evolved a fascinating array of mechanisms for conducting sexual
      reproduction. These include producing the sex-specific gametes, as well as
      mechanisms for attracting a mate, courting a mate, and getting the gametes
      together. These processes require that males and females take on dramatically
      different forms (sexual dimorphism). Here, we will explore the problem of how sex
      is determined in Drosophila, and pay particular attention to how information
      about sexual identity is used to instruct males and females to develop
      differently. Along the way, we will highlight new work that challenges some of
      the traditional views about sex determination. In Drosophila, it is commonly
      thought that every cell decides its own sex based on its sex chromosome
      constitution (XX vs. XY). However, we now know that many cell types undergo
      nonautonomous sex determination, where they are told what sex to be through
      signals from surrounding cells, independent of their own chromosomal content.
      Further, it now appears that not all cells even "know" their sex, since key
      members of the sex determination pathway are not expressed in all cells. Thus,
      our understanding of how sex is determined, and how sexual identity is used to
      create sexual dimorphism, has changed considerably.

PMID- 19118665
TI  - Drosophila germline sex determination: integration of germline autonomous cues
      and somatic signals.
AB  - The Drosophila testis and ovary are major genetically tractable systems for
      studying stem cells and their regulation. This has resulted in a deep
      understanding of germline stem cell regulation by the microenvironment, or niche.
      The male and female germline niches differ. Since sex is determined through
      different mechanisms in the soma than in the germline, genetic or physical
      manipulations can be used to experimentally mismatch somatic and germline sexual
      identities. The phenotypic consequences of these mismatches have striking
      similarities to those resulting from manipulations of signals within the niche. A
      critical role of the germline sex determination pathway may therefore be to
      ensure the proper receipt and processing of signals from the niche.

PMID- 19118666
TI  - Sexual development of the soma in the mouse.
AB  - Sex determination in mammals results in two discrete sexes, male and female. The
      sexes are genetically distinct at fertilization (XY = male and XX = female).
      However, there is little evidence for differences in their development until mid
      gestation when the gonadal primordium forms. Recent research suggests that
      signals within this tissue maintain the gonad in a bipotential state, balanced
      between two alternative fates, testis or ovary. At mid-gestation, expression of
      the Y-linked gene Sry in gonadal cells triggers the divergence of gonad
      development toward the testis pathway. The critical role of Sry may be simply to
      promote the stable expression of SOX9 in the key cell population in the gonad.
      Establishment of SOX9 in this lineage is opposed by female promoting factors that
      push the gonad toward an ovarian fate. Both the male and female sides of these
      antagonistic pathways are augmented by feedback loops and reinforcing signals
      that canalize development, once the initial choice is made. Hormones and growth
      factors produced by the developing testis regulate the male differentiation of
      the sex ducts and the external genitalia during fetal life. In contrast, the
      ovary is not required for the fetal development of female genital ducts or female
      external genitalia, as these organs develop in the absence of a gonad. At
      puberty, hormones produced by the testis or the ovary control the sex-specific
      differentiation of the musculature, mammary tissue, and body hair. Male or female
      development of the brain was previously thought to depend on hormones produced by
      the testis or ovary. However, recent evidence reveals expression differences
      between XX and XY brains prior to the time that hormones are circulating,
      suggesting that some influences on brain development may be autonomous to the
      cells of the brain.

PMID- 19118667
TI  - Development of germ cells in the mouse.
AB  - In mammals, germ cells are induced from a population of cells at the base of the
      allantois. This regulative mechanism of germ line induction depends on Bmp
      signals and a combination of epigenetic changes that silence somatic
      differentiation genes and activate pluripotency genes. RNA binding proteins are a
      conserved feature of germ cell development in mammals, and play critical roles in
      the establishment and maintenance of pluripotency. After their specification,
      germ cells move through the gut to the gonads under the influence of migratory
      and attractive cues. In the gonad, germ cells initiate sex-specific
      differentiation. Germ cells that arrive in the ovary enter meiosis, whereas germ
      cells that arrive in the testis undergo mitotic arrest. Entry into meiosis is
      controlled by retinoic acid signals that are blocked in the testis. The signals
      regulating mitotic arrest in the testis are still not completely understood, but
      likely involve RNA-binding proteins. Epigenetic reprograming occurs during
      specification, migratory stages, and sex-specific stages, when maternal and
      paternal imprints are established. The facility of transitions between germ cells
      and stem cells suggests a close relationship among their genomic programs.

PMID- 19118668
TI  - The neuroendocrine control of sex specific behavior in vertebrates: lessons from
      mammals and birds.
AB  - The question of how sex differences in behavior among vertebrates emerge and are
      expressed has been the topic of intense study for over 50 years. Convergent
      evidence from birds and mammals, primarily rodents, has provided certain common
      principles while highlighting other species-specific properties. The importance
      of early hormonal effects on the developing brain to adult behavioral profile is
      pervasive throughout the vertebrate phyla and assures that brain sex phenotype
      will match gonadal phenotype. Variation in the magnitude of differences between
      males and females in sexual behavior, parenting and aggression are influenced by
      environmental and physiological parameters. Recent advances in the cellular and
      molecular mechanisms of steroid hormones in both organizing and activating neural
      circuits to control behavior reveal a wide variety of effector pathways and
      emphasize how much we have to learn.

PMID- 19118669
TI  - Yet it is clear that to understand living systems, one must also make
      measurements of their components and interactions at all levels of biological
      organization. Preface.

PMID- 19118670
TI  - Chapter 1: In vivo applications of fluorescence correlation spectroscopy.
AB  - Fluorescence correlation spectroscopy provides a sensitive optical probe of the
      molecular dynamics of life in vivo and in vitro. The kinetics of chemical
      binding, transport, and changes in molecular conformations are detected by
      measurement of fluctuations of fluorescence emission by sensitive marker
      fluorophores. The fluorophores within a defined volume are illuminated by laser
      light that excites their fluorescence. While conventional confocal illumination
      by short-wavelength laser light is sufficient for two-dimensional targets,
      multiphoton fluorescence excitation by simultaneous quantum absorption of two or
      more long-wavelength photons of approximately 100 fs laser pulses provides the
      more precise submicron three-dimensional spatial resolution required in cells and
      tissues. Chemical kinetics, molecular aggregation, molecular diffusion, fluid
      flows, photophysical interactions, conformational fluctuations, concentration
      fluctuations, and other dynamics of biological processes can be measured and
      monitored in volumes approximately 1 mum(3) at timescales from <1 mus and upward
      for many orders of magnitude. Theory, motivations, methods, in vivo applications,
      and future directions for improvement and new applications for fluorescence
      correlation spectroscopy are summarized in this chapter.

PMID- 19118671
TI  - Chapter 2: Molecular sensors based on fluorescence resonance energy transfer to
      visualize cellular dynamics.
AB  - Visualizing a variety of signaling events in the native cellular environment is
      now possible with the advent of genetically encodable fluorescent labels like
      green fluorescent proteins made de novo by living cells themselves. The focus of
      this method chapter is on genetically encodable molecular sensors based on
      fluorescence resonance energy transfer (FRET) for visualization of cellular
      dynamics. This chapter discusses the process of developing a molecular sensor,
      from choosing donor-acceptor pairs to designing the protein modules that actually
      sense the signaling events. A few examples of biosensors are discussed to
      showcase the designs of such FRET-based sensors for live-cell imaging of
      signaling events. Subsequently, Section III covers the experimental procedure of
      DNA work, microscope instrumentation, data collection through imaging
      acquisition, data comprehension, and evaluation. Furthermore, a case study of the
      PI3K/Akt signaling pathway using a series of FRET sensors highlights the
      tremendous potential of the method in exploring relevant biological systems.

PMID- 19118673
TI  - Chapter 4: Combining microfluidics and quantitative fluorescence microscopy to
      examine pancreatic islet molecular physiology.
AB  - Pancreatic islets are functional micro-organs involved in maintaining
      normoglycemia through regulated secretion of insulin and other hormones.
      Extracellular glucose stimulates insulin secretion from islet beta-cells through
      an increase in metabolic state, which can be measured using two-photon NAD(P)H
      imaging. Extracellular glucose concentrations of >7 mM generate synchronous beta
      cell calcium (Ca(2+)) oscillations leading to pulsatile insulin secretion. Our
      studies have focused on the coupling of cells within the islet using quantitative
      fluorescence imaging of metabolic (NAD(P)H) and electrical (Ca(2+)) responses.
      This imaging requires immobilization of the tissue to achieve subcellular spatial
      and subsecond temporal resolutions. We have developed microfluidic devices to
      stimulate islets while holding them stationary against a glass coverslip. One
      device is a dual-channel microfluidic that allows heterogeneous islet stimulation
      by introducing a standing gradient in glucose concentration across the islet. The
      second device is a single channel microfluidic with the general utility to hold
      islets static. This chapter will describe the fabrication and use of these
      devices, with specific reference to their demonstrated utility for quantitative
      and dynamic imaging of living pancreatic islets. We will also highlight the
      general utility of these devices as a paradigm transferable to the study of other
      tissues.

PMID- 19118672
TI  - Chapter 3: A fluorescent window into protein folding and aggregation in cells.
AB  - Evolutionary selective pressures have tuned the efficiency of the protein-folding
      reaction in the crowded complex environment in the cell. Nevertheless, the
      fidelity of folding is imperfect, leading to off-pathway intermolecular
      interactions that compete with proper folding and to consequent formation of
      thermodynamically stable aggregates. Such aggregates constitute the
      histopathological hallmarks of many neurodegenerative pathologies. Yet, most of
      the approaches to characterize protein folding and/or misfolding are limited to
      in vitro conditions. Here, we describe a strategy to directly monitor the
      behavior of a protein in prokaryotic and eukaryotic cells. The method is based on
      incorporation of structurally non-perturbing, specific binding motifs for a bis
      arsenical fluoroscein dye, FlAsH, in sites that result in distinct dye
      fluorescence signals for the folded and unfolded states of the protein under
      study. Our approach has been developed using as a case study the predominantly
      beta-sheet intracellular lipid-binding protein, cellular retinoic acid-binding
      protein, alone or as a chimera fused to the exon 1-encoded fragment of
      huntingtin, which harbors a polyglutamine repeat tract. We have designed
      protocols to label this protein in vivo and to monitor the resulting fluorescence
      signal, which reports on any misfolding transition and formation of aggregates,
      yielding quantitatively interpretable data.

PMID- 19118674
TI  - Chapter 5: Imaging in depth: controversies and opportunities.
AB  - One enduring challenge of biological imaging is achieving depth of penetration
      into cells, tissues, and animals. How deeply can we probe and with what
      resolution and efficacy? These are critical issues as microscopists seek to push
      ever deeper, while resolving structural details and observing specific molecular
      events. In this guide to depth-appropriate modalities, standard optical platforms
      such as confocal and two-photon microscopes are considered along with
      complementary imaging modalities that range in depth of penetration. After an
      introduction to basic techniques, the trade-offs and limitations that distinguish
      competing technologies are considered, with emphasis on the visualization of
      subcellular structures and dynamic events. Not surprisingly, there are
      differences of opinion regarding imaging technologies, as highlighted in a
      section on point-scanning and Nipkow-disk style confocal microscopes. Confocal
      microscopy is then contrasted with deconvolution and multi-photon imaging
      modalities. It is also important to consider the detectors used by current
      instruments (such as PMTs and CCD cameras). Ultimately specimen properties, in
      conjunction with instrumentation, determine the depth at which subcellular
      operations and larger-scale biological processes can be visualized. Relative
      advantages are mentioned in the context of experiment planning and instrument
      purchase decisions. Given the rate at which new optical techniques are being
      invented, this report should be viewed as a snapshot of current capabilities,
      with the goal of providing a framework for thinking about new developments.

PMID- 19118675
TI  - Chapter 6: Principles and practice in electron tomography.

PMID- 19118676
TI  - Chapter 7: Total internal reflection fluorescence microscopy.
AB  - Total internal reflection fluorescence microscopy (TIRFM), also known as
      evanescent wave microscopy, is used in a wide range of applications, particularly
      to view single molecules attached to planar surfaces and to study the position
      and dynamics of molecules and organelles in living culture cells near the contact
      regions with the glass coverslip. TIRFM selectively illuminates fluorophores only
      in a very thin (less than 100 nm deep) layer near the substrate, thereby avoiding
      excitation of fluorophores outside this subresolution optical section. This
      chapter reviews the history, current applications in cell biology and
      biochemistry, basic optical theory, combinations with numerous other optical and
      spectroscopic approaches, and a range of setup methods, both commercial and
      custom.

PMID- 19118677
TI  - Chapter 8: Spatiotemporal dynamics in bacterial cells: real-time studies with
      single-event resolution.
AB  - To produce a quantitative picture of cellular life, one has to study the
      processes comprising it in individual living cells, quantifying intracellular
      dynamics with sufficient resolution to describe individual events in space and
      time. To perform such studies, we have recently developed a novel measurement
      approach, based on quantitative fluorescence microscopy, and applied it to the
      study of transcription in Escherichia coli and of the spatiotemporal dynamics of
      individual mRNA molecules in the cell (Golding and Cox, 2004, 2006a; Golding et
      al., 2005). The ability to detect individual events in real time depends on the
      engineering of an endogenous cellular process for amplifying the biological
      signal, in a way which allows signal detection to be independent of slow and
      highly stochastic cellular processes (Golding and Cox, 2006a). In this chapter,
      we describe the ingredients of our system and the way data is acquired and
      analyzed. We attempt to give general lessons for researchers who wish to
      implement a similar approach for the study of transcription in other organisms
      and, more generally, for the study of cellular processes with single-event
      resolution.

PMID- 19118678
TI  - Chapter 9: Counting proteins in living cells by quantitative fluorescence
      microscopy with internal standards.
AB  - This chapter describes how a confocal microscope can be treated as a
      spectrophotometer to measure the absolute number of fluorescent molecules in live
      cells (Wu and Pollard, 2005).(1) The method provides dynamic range of over three
      orders of magnitude for counting the number of molecules in a single cell. We
      present a step-by-step guide to measure concentrations in vivo, explaining many
      of the practical considerations for using this technique. This chapter is meant
      as a resource for cell biologists, biochemists, and biophysicists interested in
      quantifying macromolecules involved in their favorite molecular pathways in live
      cells.

PMID- 19118679
TI  - Chapter 10: Infrared and Raman microscopy in cell biology.
AB  - This chapter presents novel microscopic methods to monitor cell biological
      processes of live or fixed cells without the use of any dye, stains, or other
      contrast agent. These methods are based on spectral techniques that detect
      inherent spectroscopic properties of biochemical constituents of cells, or parts
      thereof. Two different modalities have been developed for this task. One of them
      is infrared micro-spectroscopy, in which an average snapshot of a cell's
      biochemical composition is collected at a spatial resolution of typically 25 mum.
      This technique, which is extremely sensitive and can collect such a snapshot in
      fractions of a second, is particularly suited for studying gross biochemical
      changes. The other technique, Raman microscopy (also known as Raman micro
      spectroscopy), is ideally suited to study variations of cellular composition on
      the scale of subcellular organelles, since its spatial resolution is as good as
      that of fluorescence microscopy. Both techniques exhibit the fingerprint
      sensitivity of vibrational spectroscopy toward biochemical composition, and can
      be used to follow a variety of cellular processes.

PMID- 19118680
TI  - Chapter 11: Imaging fluorescent mice in vivo using confocal microscopy.
AB  - In vivo imaging is the most direct way to uncover the dynamic events that occur
      during neural development. This approach is especially challenging in developing
      mammals where technical hurdles related to optical resolution, animal movement,
      phototoxicity, and postoperative complications need to be addressed. In our work
      concerning the process of naturally occurring synapse elimination at developing
      neuromuscular junctions, these technical issues are critical because we need to
      resolve multiple and very fine single axons that converge on the same synaptic
      site. In previous studies, we used wide-field microscopy with either intensified
      or high quantum efficiency cameras. We now have begun to use laser scanning
      confocal microscopy which improves contrast and resolution but comes with its own
      challenges. In this chapter, we describe the approaches we have taken to permit
      both rapid time-lapse (minutes to hours) and long-term time-lapse (days to
      months) to visualize the synaptic alterations associated with the development and
      maturation of the neuromuscular system.

PMID- 19118681
TI  - Chapter 12: Nanoscale biological fluorescence imaging: breaking the diffraction
      barrier.
AB  - Biological imaging has been limited by the finite resolution of light microscopy.
      Recent developments in ultra-high-resolution microscopy methods, many of which
      are based on fluorescence, are breaking the diffraction barrier; it is becoming
      possible to image intracellular protein distributions with resolution of tens of
      nanometers or better. Fluorescence photoactivation localization microscopy
      (FPALM) is an example of such an ultra-high-resolution method which can image
      living or fixed cells with demonstrated lateral resolution of better than 20 nm.
      A detailed description of the methods involved in FPALM imaging of biological
      samples is presented here, accompanied by comparison with existing methods from
      the literature.

PMID- 19118682
TI  - Chapter 13: Imaging of cells and tissues with mass spectrometry: adding chemical
      information to imaging.
AB  - Techniques that map the distribution of compounds in biological tissues can be
      invaluable in addressing a number of critical questions in biology and medicine.
      One of the newer methods, mass spectrometric imaging, has enabled investigation
      of spatial localization for a variety of compounds ranging from atomics to
      proteins. The ability of mass spectrometry to detect and differentiate a large
      number of unlabeled compounds makes the approach amenable to the study of complex
      biological tissues. This chapter focuses on recent advances in the
      instrumentation and sample preparation protocols that make mass spectrometric
      imaging of biological samples possible, including strategies for both tissue and
      single-cell imaging using the following mass spectrometric ionization methods:
      matrix-assisted laser desorption/ionization, secondary ion, electrospray, and
      desorption electrospray.

PMID- 19118683
TI  - Chapter 14: Electron microscopy of hydrated samples.
AB  - Conventional electron microscopy offers a substantial resolution advantage over
      light microscopy, but requires difficult and often destructive preparation
      techniques. Recent advances in electron microscopy allow for imaging of hydrated
      samples, retaining the resolution advantage while removing the difficulty in
      preparation. Two new techniques, environmental scanning electron microscopy and
      wet electron microscopy offer this advantage, allowing for new possibilities in
      biological imaging.

PMID- 19118684
TI  - Chapter 15: Live-cell single-molecule force spectroscopy.
AB  - We describe a method to measure the kinetics and micromechanical properties of
      individual receptor-ligand bonds formed between two living cells. Using living
      cells rather than recombinant proteins ensures that the orientation, surface
      density, and posttranslational modifications of the probed receptors are
      physiological and that their regulated attachment to the cytoskeleton can occur.
      A cell is tethered to a flexible cantilever and brought into contact with cells
      adherent to a substratum before being pulled at a controlled retraction velocity.
      Measurements of bond rupture forces and associated bond loading rates over an
      extended range of retraction velocities allow us to compute precisely the tensile
      strength, reactive compliance, lifetime, and dissociation rate of individual
      intercellular receptor-ligand bonds. We also describe tests of specificity and
      Monte Carlo simulations, which ensure that measurements obtained by this method
      correspond to a single type of intercellular adhesion bond. We illustrate this
      live-cell single molecule force spectroscopy assay by characterizing homotypic
      bonds composed of vascular endothelial -cadherin pairs formed between living
      endothelial cells. This versatile assay could be used to establish the molecular
      principles that drive a wide range of important physiological processes involving
      receptor-mediated intercellular adhesion, such as the immunological synapse
      between a lymphocyte and an antigen-presenting cell and synaptic interactions
      between neuron cells, and pathological processes resulting in altered
      intercellular adhesion.

PMID- 19118685
TI  - Chapter 16: Magnetic manipulation for force measurements in cell biology.
AB  - Life is a mechanical process. Cells, tissues, and bodies must act within their
      environments to grow, divide, move, communicate, and defend themselves. The
      stiffness and viscosity of cells and biologic materials will vary depending upon
      a wide variety of variables including for example environmental conditions,
      activation of signaling pathways, stage of development, gene expression. By
      pushing and pulling cells or materials such as mucus or extracellular matrix, one
      can learn about their mechanical properties. By varying the conditions, signaling
      pathways or genetic background, one can also assess how the response of the cell
      or material is modulated by that pathway. Magnetic particles are available
      commercially in many useful sizes, magnetic contents, and surface chemistries.
      The variety of surface chemistries allow forces to be applied to a specimen
      through specific linkages such as receptors or particular proteins, allowing the
      biologist to ask fundamental questions about the role of those linkages in the
      transduction of force or motion. In this chapter, we discuss the use of a
      magnetic system designed to apply a wide range of forces and force patterns fully
      integrated into a high numerical aperture inverted fluorescence microscope. Fine,
      thin and flat magnetic poles allow the use of high magnification microscope
      objectives, and flexible software to control the direction and pattern of applied
      forces supports a variety of experimental situations. The system can be coupled
      with simple video acquisition for medium-bandwidth, two-dimensional particle
      tracking. Alternatively, the system can be coupled with a laser tracking and
      position feedback system for higher resolution, high bandwidth, three-dimensional
      tracking.

PMID- 19118686
TI  - Chapter 17: Application of laser tweezers to studies of membrane-cytoskeleton
      adhesion.
AB  - Interaction between the plasma membrane and cytoskeleton is important in
      regulating cell functions such as lamellipodial extension, cell motility, and
      endocytosis. Here, we describe a method to determine plasma membrane-cytoskeleton
      adhesion by measuring tether force using laser optical tweezers. We show the
      basic components and instrumental setup of a laser optical tweezers system which
      is used to pull thin membrane tethers from the cell surface using one micron
      polystyrene beads coated with membrane binding ligands. We also show an
      application of tether force measurements in elucidating regulation of membrane
      cytoskeleton adhesion. That phosphatidylinositol-4,5-biphosphate (PIP2) may play
      an important role in regulating membrane-cytoskeleton adhesion is suggested by
      correlating the plasma membrane concentration of PIP2 with membrane-cytoskeleton
      adhesion using tether force measurements. The assay described here enables us to
      investigate mechanochemical components of many important cellular processes, such
      as lamellipodial extension, cell motility, membrane resealing after cell
      wounding, and endocytosis. Furthermore, this method could be used to establish
      the link between biochemical function and physical properties of the plasma
      membrane which drives these dynamic cellular processes.

PMID- 19118687
TI  - Chapter 18: Sensing cytoskeletal mechanics by ballistic intracellular
      nanorheology (BIN) coupled with cell transfection.
AB  - Key processes in normal and diseased cells depend directly or indirectly on the
      viscoelastic properties of the cytoplasm. Particle-tracking microrheology is a
      highly versatile method that measures the viscoelastic properties of cytoplasm
      directly by tracking fluorescent nanoparticles embedded in the cytoskeleton with
      high spatial and temporal resolutions. Here we present a new method that combines
      cell transfection, ballistic injection, and particle-tracking microrheology to
      monitor changes in cytoplasmic micromechanics following controlled changes in
      protein expression. We demonstrate that cells transfected with GFP (green
      fluorescent protein) display viscoelastic properties identical to untransfected
      fibroblasts, that low levels of expression of GFP-alpha-actinin do not affect
      cell microrheology, and that the transient transfection with GFP-C3 transferase
      reduces the elasticity of the cytoplasm of fibroblasts to a similar extent as C3
      transferase toxin, which de-activates the GTPase Rho. Combining cell transfection
      with particle-tracking microrheology opens the way to quantitative, single live
      cell mechanical studies where stable cell lines cannot be easily established, but
      where commonly used transfections can be exploited to manipulate cytoskeletal
      organization.

PMID- 19118689
TI  - Chapter 20: Automated spatial mapping of microtubule catastrophe rates in fission
      yeast.
AB  - Microtubules (MTs) are cytoskeletal polymers whose spatial organization is
      dynamically regulated, depending on their biological function during different
      cell cycle stages. Growing MT ends are, for example, specifically targeted
      towards the cortex of motile or growing cells during interphase or towards
      chromosomal attachment sites during mitosis. An important parameter that cells
      use to control the average length of MTs, and thus the distance over which these
      targeting processes may operate, is the so-called catastrophe frequency f(cat):
      the rate at which MTs switch from a growing to a shrinking state. To understand
      how spatial targeting and the local control of f(cat) are related, quantitative
      in vivo measurements are needed that allow for the measurement of f(cat) in a
      spatially resolved way. Since catastrophes are intrinsically stochastic events,
      it is essential to acquire enough statistics to obtain the underlying rate
      constant f(cat). Here, we present automated image processing methodology,
      developed using GFP-tubulin expressing fission yeast cells, that makes it
      possible to measure f(cat) both spatially resolved and with high statistical
      accuracy. Although certain aspects of the analysis are specific to the system
      under investigation the basic concepts of the methodology are applicable to any
      kind of movies of fluorescently labeled MTs.

PMID- 19118688
TI  - Chapter 19: Mechanical response of cytoskeletal networks.
AB  - The cellular cytoskeleton is a dynamic network of filamentous proteins,
      consisting of filamentous actin (F-actin), microtubules, and intermediate
      filaments. However, these networks are not simple linear, elastic solids; they
      can exhibit highly nonlinear elasticity and a thermal dynamics driven by ATP
      dependent processes. To build quantitative mechanical models describing complex
      cellular behaviors, it is necessary to understand the underlying physical
      principles that regulate force transmission and dynamics within these networks.
      In this chapter, we review our current understanding of the physics of networks
      of cytoskeletal proteins formed in vitro. We introduce rheology, the technique
      used to measure mechanical response. We discuss our current understanding of the
      mechanical response of F-actin networks, and how the biophysical properties of F
      actin and actin cross-linking proteins can dramatically impact the network
      mechanical response. We discuss how incorporating dynamic and rigid microtubules
      into F-actin networks can affect the contours of growing microtubules and
      composite network rigidity. Finally, we discuss the mechanical behaviors of
      intermediate filaments.

PMID- 19118690
TI  - Chapter 21: Quantitative fluorescence lifetime imaging in cells as a tool to
      design computational models of ran-regulated reaction networks.
AB  - The understanding of cell function often requires that complex intracellular
      pathways are considered in quantitative terms. The access to precise measurement
      of activities in live cells is increasingly provided by the advances in
      fluorescence lifetime imaging microscopy (FLIM) of Forster (or fluorescence)
      resonance energy transfer (FRET)-based molecular biosensors. We discuss how
      quantitative in vivo imaging can be combined with in vitro biochemical
      characterization to develop computational systems models simulating the behavior
      of biochemical networks. We describe the application of such approach in
      computational modeling of the Ran GTPase function in mitotic spindle assembly.
      The RanGTP concentration gradient surrounding mitotic chromosomes induces the
      formation of a gradient of spindle assembly factors (SAFs) activated by RanGTP
      induced release from inhibitory complexes of SAFs with importin beta. To
      visualize the gradient of activated SAFs in live cells, we used FLIM to detect
      the signal of a FRET-based biosensor that reports its RanGTP-induced liberation
      from importin beta. We review the technical aspects of FRET measurements by FLIM
      and discuss the step-wise design of systems models aided by quantitative imaging.
      As evidenced by the example of mitotic Ran gradient studies, the computational
      simulations are a powerful tool to test new hypotheses on biological function.

PMID- 19118691
TI  - Chapter 22: Quantitation of protein-protein interactions: confocal FRET
      microscopy.
AB  - Forster resonance energy transfer (FRET) is an effective and high resolution
      method to monitor protein-protein interactions in live or fixed specimens. FRET
      can be used to estimate the distance between interacting protein molecules in
      vivo or in vitro using laser-scanning confocal FRET microscopy. The spectral
      overlap of donor and acceptor-essential for FRET-also generates a contamination
      of the FRET signal, which should be removed in order to carry out quantitative
      data analysis with confidence. Quantitative FRET data analysis addresses the
      wealth of information contained in the data set, once optimized FRET imaging has
      been completed. In this chapter, we describe step-by-step what the issues are in
      quantitative FRET data analysis, using membrane receptor trafficking and
      organization as an example. The assays described are applicable to many other
      biological applications.

PMID- 19118692
TI  - Chapter 23: Stochastic modeling methods in cell biology.
AB  - Stochastic methods have been a staple for understanding complex systems in
      chemistry and physics. In the biological context, they are useful for
      understanding phenomena ranging from molecular-level fluctuations to cellular
      movement. We review the basic formalism behind stochastic methods and outline how
      they can be implemented for quantifying gene expression, movement of molecular
      motors, and the dynamics of cytoplasmic components. We show that stochastic
      methods are quantitative checks for proposed molecular mechanisms and can pose
      new questions for experiments. Structural information of cellular components can
      be incorporated into stochastic models to reveal new biological insights.

PMID- 19118693
TI  - Chapter 24: Computational modeling of self-organized spindle formation.
AB  - In this chapter, we provide a derivation and computational details of a
      biophysical model we introduced to describe the self-organized mitotic spindle
      formation properties in the chromosome dominated pathway studied in Xenopus
      meiotic extracts. The mitotic spindle is a biological structure composed of
      microtubules. This structure forms the scaffold on which mitosis and cytokinesis
      occurs. Despite the seeming mechanical simplicity of the spindle itself, its
      formation and the way in which it is used in mitosis and cytokinesis is complex
      and not fully understood. Biophysical modeling of a system as complex as mitosis
      requires contributions from biologists, biochemists, mathematicians, physicists,
      and software engineers. This chapter is written for biologists and biochemists
      who wish to understand how biophysical modeling can complement a program of
      biological experimentation. It is also written for a physicist, computer
      scientist, or mathematician unfamiliar with this class of biological physics
      model. We will describe how we built such a mathematical model and its numerical
      simulator to obtain results that agree with many of the results found
      experimentally. The components of this system are large enough to be described in
      terms of coarse-grained approximations. We will discuss how to properly model
      such systems and will suggest effective tradeoffs between reliability, simulation
      speed, and accuracy. At all times we have in mind the realistic biophysical
      properties of the system we are trying to model.

PMID- 19118694
TI  - The myth of clinical precision.

PMID- 19118695
TI  - Influence of blue-light-filtering intraocular lenses on color perception and
      contrast acuity.
AB  - PURPOSE: To compare contrast acuity at different illumination levels and color
      vision and the subjective impression in patients after bilateral cataract surgery
      with a mixed implantation of a blue-light-filtering and an ultraviolet (UV)
      filtering intraocular lens (IOL). DESIGN: Randomized, controlled, double-masked,
      and bilateral study with intraindividual comparison. PARTICIPANTS: This study
      included 48 eyes of 24 consecutive patients with age-related cataract. METHODS:
      Each patient had standardized small incision cataract surgery with IOL
      implantation into the capsular bag. Patients were randomly assigned to receive a
      blue-light-filtering Hoya AF-1 (UY) YA-60BB IOL in one eye and a UV-filtering
      Hoya AF-1 (UV) VA-60BB IOL (Hoya Medical Europe, Frankfurt/Main, Germany) in the
      contralateral eye. Contrast acuity was measured at illumination levels of 500, 5,
      and 0.5 lux and contrast levels of 100%, 50%, 25%, 12.5%, and 6.25%. Color vision
      was assessed using the Lanthony desaturated D-15 test, the Lanthony new color
      test (Munsell chroma 2 and 4), and an anomaloscope. Blue/yellow foveal threshold
      was tested applying short-wave automated perimetry. The subjective visual
      impression of patients was evaluated using a questionnaire. MAIN OUTCOME
      MEASURES: Contrast acuity, color vision, and foveal threshold. RESULTS: The blue
      light-filtering IOLs had worse contrast acuity (P = 0.0004) and foveal threshold
      (P = 0.008) compared with the UV-filtering IOLs. Color vision tests and high
      contrast visual acuity did not show any statistically significant differences
      between IOLs (P>0.05). On questioning, 3 of 24 patients noticed a difference
      between the implanted IOLs concerning visual impression. CONCLUSIONS: This study
      shows that blue-light-filtering IOLs negatively affect contrast acuity and
      blue/yellow foveal threshold when compared with UV-filtering IOLs. Although the
      differences were small, the results suggest bilateral implantation of the same
      IOL type and avoidance of a mixed implantation of a blue-light-filtering IOL in
      one and a non-blue-light-filtering IOL in the contralateral eye in patients with
      high demands in color vision. FINANCIAL DISCLOSURE(S): The author(s) have no
      proprietary or commercial interest in any materials discussed in this article.

PMID- 19118697
TI  - A systematic correlation of angiography and high-resolution optical coherence
      tomography in diabetic macular edema.
AB  - PURPOSE: To correlate leakage patterns in fluorescein angiography (FA) images and
      retinal morphologic features in high-definition optical coherence tomography (HD
      OCT) images in diabetic macular edema. DESIGN: Prospective pilot study and case
      series. PARTICIPANTS: Nine consecutive patients (10 eyes) with diabetic macular
      edema. METHODS: All patients were examined using FA (HRA 2; Heidelberg
      Engineering) and HD OCT (Carl Zeiss Meditec; resolution, 512x128 pixels, 5.8x5.8
      mm, and high-resolution scans consisting of 4096 A scans) on the same day. Using
      Adobe Photoshop (CS2 Version 9.0; Adobe Systems Incorporated, San Jose, CA) a
      grid containing 15x7 fields was superimposed on the HD OCT en face image and a
      late-phase FA image according to retinal landmarks. In each patient, a
      standardized analysis of 105 subfields was performed to provide a
      characterization of the type of vascular leakage in FA and the associated retinal
      morphologic changes in corresponding locations. MAIN OUTCOME MEASURES:
      Angiographic leakage type and structural alteration in retinal morphologic
      features in OCT. RESULTS: There was a high consistency between FA and OCT in the
      petaloid pattern of hyperfluorescence that correlated with the presence of large
      cystic spaces in the outer nuclear layer (ONL) and the outer plexiform layer
      (OPL) with or without subretinal fluid in 30.4% and 69.6% of graded fields,
      respectively. A honeycomblike pattern of hyperfluorescence was associated with
      swelling and cystic spaces in ONL, OPL, the inner nuclear, and the inner
      plexiform layer in 71.4% of graded fields. Diffuse patterns of hyperfluorescence
      did not correlate with characteristic retinal changes in HD OCT, but rather
      showed diversity in the type of morphologic alteration. The presence of central
      fluid pooling, such as subretinal fluid, could be identified only by HD OCT and
      not by FA. CONCLUSIONS: In the examined patients, a petaloid pattern and a
      honeycomb pattern of hyperfluorescence observed in FA were found to correlate to
      characteristic changes in HD OCT, whereas a diffuse leakage pattern was
      associated with nonuniform changes in retinal morphologic features. FINANCIAL
      DISCLOSURE(S): The author(s) have no proprietary or commercial interest in any
      materials discussed in this article.

PMID- 19118698
TI  - Association of vitreous inflammatory factors with diabetic macular edema.
AB  - PURPOSE: To evaluate the association between vitreous inflammatory factors and
      the severity of diabetic macular edema (DME). DESIGN: Retrospective case-control
      study. PARTICIPANTS: Fifty-three patients with DME, 15 patients with nondiabetic
      ocular disease, and 8 diabetic patients without retinopathy. METHODS: Vitreous
      fluid samples were obtained during vitreoretinal surgery, and the levels of
      vascular endothelial growth factor (VEGF), intercellular adhesion molecule (ICAM)
      1, interleukin (IL)-6, monocyte chemotactic protein (MCP)-1, and pigment
      epithelium-derived factor (PEDF) were measured by enzyme-linked immunosorbent
      assay. Multivariate analysis was performed to assess the association of these
      factors with the severity of DME. MAIN OUTCOME MEASURES: Vitreous fluid levels of
      inflammatory factors. RESULTS: Vitreous fluid levels of VEGF, ICAM-1, IL-6, and
      MCP-1 were significantly higher in patients with DME than in nondiabetic patients
      (P<0.05, all respectively) or diabetic patients without retinopathy (P<0.05, all
      respectively). In contrast, the PEDF level was significantly lower in patients
      with DME than in nondiabetic patients (P<0.05) or diabetic patients without
      retinopathy (P<0.05). Vitreous levels of VEGF, ICAM-1, IL-6, and MCP-1 were
      significantly higher in patients with hyperfluorescent DME than in those with
      minimally fluorescent DME (P = 0.0018, P = 0.0022, P = 0.0032, and P = 0.0053,
      respectively). Conversely, the vitreous level of PEDF was significantly lower in
      hyperfluorescent DME than in minimally fluorescent DME (P = 0.0134). Vitreous
      levels of VEGF, ICAM-1, IL-6, MCP-1, and PEDF were significantly correlated with
      the retinal thickness at the central fovea (P<0.0001, P<0.0001, P = 0.0282, P =
      0.0009, and P = 0.0466, respectively). VEGF and ICAM-1 had a stronger influence
      on the severity of DME than the other factors (P = 0.0004 and P = 0.0372,
      respectively). CONCLUSIONS: Vitreous fluid levels of VEGF, ICAM-1, IL-6, MCP-1,
      and PEDF were related to retinal vascular permeability and the severity of DME.
      VEGF and ICAM-1 had a stronger influence than the other factors. FINANCIAL
      DISCLOSURE(S): The authors have no proprietary or commercial interest in any
      materials discussed in this article.

PMID- 19118696
TI  - Ranibizumab versus verteporfin photodynamic therapy for neovascular age-related
      macular degeneration: Two-year results of the ANCHOR study.
AB  - OBJECTIVE: The 2-year, phase III trial designated Anti-vascular endothelial
      growth factor (VEGF) Antibody for the Treatment of Predominantly Classic
      Choroidal Neovascularization (CNV) in Age-related Macular Degeneration (ANCHOR)
      compared ranibizumab with verteporfin photodynamic therapy (PDT) in treating
      predominantly classic CNV. DESIGN: Multicenter, international, randomized, double
      masked, active-treatment-controlled clinical trial. PARTICIPANTS: Patients with
      predominantly classic, subfoveal CNV not previously treated with PDT or
      antiangiogenic drugs. INTERVENTION: Patients were randomized 1:1:1 to verteporfin
      PDT plus monthly sham intraocular injection or to sham verteporfin PDT plus
      monthly intravitreal ranibizumab (0.3 mg or 0.5 mg) injection. The need for PDT
      (active or sham) retreatment was evaluated every 3 months using fluorescein
      angiography (FA). MAIN OUTCOME MEASURES: The primary, intent-to-treat efficacy
      analysis was at 12 months, with continued measurements to month 24. Key measures
      included the percentage losing <15 letters from baseline visual acuity (VA) score
      (month 12 primary efficacy outcome measure), percentage gaining >or=15 letters
      from baseline, and mean change over time in VA score and FA-assessed lesion
      characteristics. Adverse events were monitored. RESULTS: Of 423 patients (143
      PDT, 140 each in the 2 ranibizumab groups), the majority (>or=77% in each group)
      completed the 2-year study. Consistent with results at month 12, at month 24 the
      VA benefit from ranibizumab was statistically significant (P<0.0001 vs. PDT) and
      clinically meaningful: 89.9% to 90.0% of ranibizumab-treated patients had lost
      <15 letters from baseline (vs. 65.7% of PDT patients); 34% to 41.0% had gained
      >or=15 letters (vs. 6.3% of PDT group); and, on average, VA was improved from
      baseline by 8.1 to 10.7 letters (vs. a mean decline of 9.8 letters in PDT group).
      Changes in lesion anatomic characteristics on FA also favored ranibizumab (all
      comparisons P<0.0001 vs. PDT). Overall, there was no imbalance among groups in
      rates of serious ocular and nonocular adverse events. In the pooled ranibizumab
      groups, 3 of 277 (1.1%) patients developed presumed endophthalmitis in the study
      eye (rate per injection = 3/5921 [0.05%]). CONCLUSIONS: In this 2-year study,
      ranibizumab provided greater clinical benefit than verteporfin PDT in patients
      with age-related macular degeneration with new-onset, predominantly classic CNV.
      Rates of serious adverse events were low. FINANCIAL DISCLOSURE(S): Proprietary or
      commercial disclosure may be found after the references.

PMID- 19118699
TI  - Effect of intravitreal bevacizumab injection on aqueous humor cytokine levels in
      clinically significant macular edema.
AB  - PURPOSE: To determine the effect of intravitreal bevacizumab (Avastin, Genentech,
      Inc., San Francisco, CA) injection on aqueous humor cytokine levels in clinically
      significant macular edema (CSME). DESIGN: Retrospective, comparative study.
      PARTICIPANTS: Seventeen eyes undergoing intravitreal injection for CSME and 11
      eyes undergoing cataract surgery as negative controls. Nine patients with CSME
      were naive to intravitreal bevacizumab injection (CSME group 1), and 8 patients
      previously received 1 intravitreal bevacizumab injection at a mean of 9.6+/-1.4
      weeks earlier (CSME group 2). METHODS: Aqueous humor samples were collected
      before performing intravitreal injection in the CSME group and during cataract
      surgery in the control group. Aqueous cytokine levels were determined by
      immunoassay using multianalyte biochip array technology. MAIN OUTCOME MEASURES:
      The concentration of cytokines in the aqueous humor was recorded as a mean (+/-
      standard deviation) in CSME groups 1 and 2 and the control group. Correlations of
      aqueous humor cytokine levels were evaluated. RESULTS: Significantly higher
      levels of interleukin (IL)-6, IL-8, and monocyte chemoattractant protein (MCP)-1
      were noted in patients with CSME compared with controls. Although higher vascular
      endothelial growth factor (VEGF) levels were noted in CSME group 1 (P = 0.001), a
      lower level of VEGF was noted after intravitreal bevacizumab injection in CSME
      group 2 (P = 0.004) compared with the control group. VEGF levels were also lower
      in CSME group 2 compared with CSME group 1 (P = 0.001). In CSME group 2, a
      significant negative correlation was observed between VEGF and IL-6 (rho = 
      0.833, P = 0.01) and VEGF and MCP-1 (rho = -0.736, P = 0.037). CONCLUSIONS:
      Significantly higher levels of IL-6, IL-8, VEGF, and MCP-1 were noted in the
      aqueous humor of CSME. However, recurrence of macular edema was noted with
      significantly lower concentrations of VEGF after a single intravitreal injection
      of bevacizumab. This suggests the potential importance of IL-6 and MCP-1 in the
      pathogenesis of CSME. FINANCIAL DISCLOSURE(S): The author(s) have no proprietary
      or commercial interest in any materials discussed in this article.

PMID- 19118700
TI  - Vitreous levels of interleukin-6 and vascular endothelial growth factor in
      macular edema with central retinal vein occlusion.
AB  - OBJECTIVE: To investigate whether interleukin (IL)-6 or vascular endothelial
      growth factor (VEGF) influences macular edema in patients with central retinal
      vein occlusion (CRVO). DESIGN: Retrospective case-control study. PARTICIPANTS:
      Twenty-seven patients who had macular edema with CRVO and 16 patients with
      nonischemic ocular diseases (control group). METHODS: Retinal ischemia was
      evaluated by measuring the area of capillary nonperfusion using fluorescein
      angiography and the public domain Scion Image program, and macular edema was
      examined by optical coherence tomography. Vitreous fluid samples were obtained at
      pars plana vitrectomy. VEGF and IL-6 levels in vitreous fluid and plasma were
      determined with enzyme-linked immunosorbent assay kits. MAIN OUTCOME MEASURES:
      Vitreous fluid levels of IL-6 and VEGF. RESULTS: The vitreous fluid levels of
      VEGF (median: 435 pg/ml) and IL-6 (median: 51.2 pg/ml) were significantly higher
      in the patients with CRVO than in the control group (median: 62.4 pg/ml and 1.07
      pg/ml, respectively; P = 0.0046 and P<0.0001, respectively). The vitreous fluid
      level of VEGF was significantly correlated with that of IL-6 (P = 0.0029).
      Vitreous fluid levels of both VEGF and IL-6 were significantly higher in patients
      with CRVO who had retinal ischemia than in those without ischemia (P<0.0001 and P
      = 0.0003, respectively). Vitreous fluid levels of VEGF and IL-6 were also
      significantly correlated with the severity of macular edema (P = 0.0014 and P =
      0.0047, respectively). CONCLUSIONS: Both IL-6 and VEGF were elevated in the
      vitreous fluid of patients with ischemic CRVO and macular edema. VEGF may
      increase vascular permeability in patients with macular edema and CRVO, whereas
      IL-6 may also contribute by acting together with or via VEGF. FINANCIAL
      DISCLOSURE(S): The author(s) have no proprietary or commercial interest in any
      materials discussed in this article.

PMID- 19118701
TI  - I-125 brachytherapy for choroidal melanoma photographic and angiographic
      abnormalities: the Collaborative Ocular Melanoma Study: COMS Report No. 30.
AB  - OBJECTIVES: (1) To summarize the protocol used for grading features of
      postradiation abnormalities from fundus photographs and fluorescein angiograms of
      patients enrolled in the Collaborative Ocular Melanoma Study (COMS); (2) to
      document the prevalence of features of interest in the posterior pole of these
      eyes during 8 years of follow-up; and (3) to investigate baseline patient, tumor,
      and treatment characteristics associated with posterior pole features. DESIGN:
      Observational case series within a randomized, multicenter clinical trial.
      PARTICIPANTS: We evaluated 650 patients who were assigned to and received iodine
      125 brachytherapy in the COMS for medium-sized tumors. METHODS: Color fundus
      photographs and fluorescein angiograms were taken at baseline and 2, 5, and 8
      years; 30 features were graded according to a standard protocol. MAIN OUTCOME
      MEASURES: Prevalence at selected time intervals of fundus photographic features
      associated with retinopathy and optic neuropathy. RESULTS: The percentage of
      patients with >/=1 feature of interest was 49.2% at baseline, 84.4% at 2 years,
      91.2% at 5 years, and 90.7% at 8 years. The most frequent findings across all
      follow-up examinations were macular microaneurysms (75.6% of examinations),
      macular angiographic leakage (75.1%), and optic disc hyperfluorescence (62.8%).
      The median number of features present increased significantly with each follow-up
      to a maximum of 7 features at 8 years. The prevalence of neovascularization of
      the disc at 5 years was 5.2%. The prevalence of optic neuropathy at 5 years was
      27.4%. Prognostic factors for more prevalent and severe posterior pole
      abnormalities were diabetes, tumor location close to both optic nerve and foveal
      avascular zone, and greater dose of radiation to the foveola and optic nerve
      head. CONCLUSIONS: The amount and severity of retinopathy and optic neuropathy
      after iodine-125 brachytherapy increased through 8 years of follow-up. Assessment
      of photographs and angiograms taken in accord with a standard protocol provided
      reliable estimates of rates of development of features of retinopathy and optic
      neuropathy in eyes treated using the COMS brachytherapy protocol. Our findings
      support earlier reports that tumor factors in addition to radiation treatment may
      contribute to posterior pole abnormalities. FINANCIAL DISCLOSURE(S): The authors
      have no proprietary or commercial interest in any materials discussed in this
      article.

PMID- 19118702
TI  - Primary treatment of acute dacryocystitis by endoscopic dacryocystorhinostomy
      with silicone intubation guided by a soft probe.
AB  - PURPOSE: To investigate the suitability of cold steel endonasal endoscopic
      dacryocystorhinostomy (EES-DCR) with circular bicanalicular intubation with
      silicone tubes (CBIST) guided by a soft probe for the primary treatment of acute
      purulent dacryocystitis (APD). DESIGN: Prospective, randomized, interventional
      case series. PARTICIPANTS: Seventy-two patients (59 females, 13 males) with a
      median presenting age of 55+/-12 years (range, 28-71 years). METHODS: Eighty-four
      patients with unilateral APD were equally and randomly divided into 2 groups.
      Cold steel EES-DCR was performed after the lacrimal abscess formation, and
      external dacryocystorhinostomy (E-DCR) was performed 1 to 2 weeks after
      resolution of the acute inflammation. In both groups, CBIST guided by a soft
      probe was performed and the silicone tubes were kept in the lacrimal passages for
      3 months. Postoperative follow-up ranged from 12 to 24 months. Outcomes were
      compared between both groups, considering resolution time for external acute
      inflammation, success rate of free lacrimal passage reconstruction, and lack of
      complications as indicators of treatment suitability. MAIN OUTCOME MEASURES: Time
      for resolution of the external acute inflammation, success rate of free lacrimal
      passage reconstruction, and complications. RESULTS: In this study, complete
      postoperative data were acquired from 40 patients in the EES-DCR group and from
      32 patients in the E-DCR group, and the outcomes were compared. Acute
      inflammation resolved more quickly in the EES-DCR group than in the E-DCR group
      (P<0.05). Ostium patency at 12 months after silicone tube removal was achieved in
      significantly more patients in the EES-DCR group (36/40 [90%]) than in the E-DCR
      group (21/32 [65.7%]; P<0.01). In the EES-DCR group, lacrimal passage
      reconstruction failed because of intranasal ostial closure in 3 patients and
      because of common canaliculus obstruction in 1 patient. In the E-DCR group,
      lacrimal passage reconstruction failed because of intranasal ostial closure in 3
      patients, lacrimal sac fibrosis, granulation, or both in 6 patients, and common
      canaliculus obstruction in 2 patients. Other than the slight laceration of the
      inferior puncta, no significant complications arose from the treatments.
      CONCLUSIONS: Cold steel EES-DCR with CBIST guided by a soft probe is a promising
      alternative for the primary treatment of APD with abscess formation. FINANCIAL
      DISCLOSURE(S): The authors have no proprietary or commercial interest in any
      materials discussed in this article.

PMID- 19118703
TI  - Uveal schwannoma surgery.

PMID- 19118704
TI  - Corneal endotheliitis.

PMID- 19118705
TI  - Achromobacter keratopathy.

PMID- 19118706
TI  - TGF-beta(2) antibody in trabeculectomy.

PMID- 19118707
TI  - Cost-effectiveness.

PMID- 19118708
TI  - Aspirin and dry eye?

PMID- 19118710
TI  - Pharmacokinetics.

PMID- 19118713
TI  - Dengue optic neuropathy.

PMID- 19118714
TI  - Upper eyelid laxity.

PMID- 19118716
TI  - Mobilization of bone marrow-derived Oct-4+ SSEA-4+ very small embryonic-like stem
      cells in patients with acute myocardial infarction.
AB  - OBJECTIVES: This study sought to assess of the mobilization of nonhematopoietic
      very small embryonic-like stem cells (VSELs) in acute myocardial infarction (MI).
      BACKGROUND: Acute MI induces mobilization of bone marrow stem cells. Recently, a
      rare population of VSELs, expressing markers of embryonic pluripotent stem cells
      (PSCs), was identified in adult murine bone marrow and human umbilical cord
      blood. METHODS: Thirty-one patients with acute MI and 30 healthy subjects were
      enrolled. Blood was sampled on admission, after 24 h, and 5 days later.
      Erythrocytes were lysed and lin(-)CD45(-) VSELs were isolated using a live cell
      sorting system (FACSAria, Beckton Dickinson, San Jose, California). RESULTS: In
      healthy subjects the median number of circulating VSELs was very low (median 0.8
      [range 0 to 1.3]) cells/microl. In acute MI, VSELs were mobilized early (median
      2.7 [range 0.2 to 3.9] cells/microl; p < 0.001) and remained elevated after 24 h
      and 5 days (median 4.7 [range 0.2 to 6.4] cells/microl; p < 0.003, and median 2.6
      [range 0.3 to 3.6] cells/microl; p < 0.03, respectively). The mobilization of
      VSEL was significantly reduced in patients older than 50 years and with diabetes
      in comparison with younger and nondiabetic patients. Circulating VSELs were small
      (7 to 8 microm) and enriched in the messenger ribonucleic acid of PSC markers
      (Oct-4, Nanog), cardiac lineage (GATA-4, Nkx2.5/Csx, MEF2C), and endothelial (VE
      cadherin) markers. The presence of PSC markers (Oct-4, SSEA-4) and the chemokine
      receptor CXCR4 in circulating VSELs was confirmed at the protein level by
      immunofluorescent staining and ImageStream system (Amnis Corporation, Seattle,
      Washington) analysis. CONCLUSIONS: Acute MI induced mobilization of VSELs
      expressing pluripotent markers, early cardiac and endothelial markers, and
      chemokine receptor CXCR4.

PMID- 19118718
TI  - Declining in-hospital mortality and increasing heart failure incidence in elderly
      patients with first myocardial infarction.
AB  - OBJECTIVES: The purpose of this study was to examine the long-term incidence of
      heart failure (HF) in elderly patients with myocardial infarction (MI).
      BACKGROUND: In-hospital HF is common after MI and is associated with poor short
      term prognosis. Limited data exist concerning the long-term incidence or
      prognosis of HF after MI, particularly in the era of coronary revascularization.
      METHODS: A population-based cohort of 7,733 patients > or = 65 years of age
      hospitalized for a first MI (International Classification of Diseases-9th
      Revision-Clinical Modification code 410.x) and without a prior history of HF was
      established between 1994 and 2000 in Alberta, Canada, and followed up for 5
      years. RESULTS: During the index MI hospitalization, 2,831 (37%) MI patients were
      diagnosed with new HF and 1,024 (13%) died. Among hospital survivors who did not
      have HF during their index hospitalization (n = 4,291), an additional 3,040
      patients (71%) developed HF by 5 years, 64% of which occurred in the first year.
      In total, 5,871 (76%) elderly patients who survived their first MI developed HF
      over 5 years. Among those who survived the index hospitalization, the 5-year
      mortality rate was 39.1% for those with HF during the index MI hospitalization
      compared with 26.7% among those without HF (p < 0.0001) during the index MI
      hospitalization. Over the study period, the 5-year mortality rate after MI
      decreased by 28%, whereas the 5-year rate of HF increased by 25%. CONCLUSIONS: In
      this large cohort of elderly patients without a history of HF, HF developed in
      three-quarters in the 5 years after their first MI; this proportion increased
      over time as peri-MI mortality rates declined. New-onset HF significantly
      increases the mortality risk among these patients.

PMID- 19118717
TI  - A big promise from the very small identification of circulating embryonic stem
      like pluripotent cells in patients with acute myocardial infarction.

PMID- 19118719
TI  - Increasing post-myocardial infarction heart failure incidence in elderly patients
      a call for action.

PMID- 19118720
TI  - Prevention of recurrent lone atrial fibrillation by the angiotensin-II converting
      enzyme inhibitor ramipril in normotensive patients.
AB  - OBJECTIVES: The aim of the present study was to verify whether angiotensin-II
      converting enzyme (ACE) inhibition is also effective in preventing relapses of
      lone atrial fibrillation (LAF), that is, in the absence of hypertension and/or
      heart disease. BACKGROUND: Several studies have shown that ACE inhibitors are
      effective in preventing atrial fibrillation (AF) relapses in patients with
      arterial hypertension or several forms of heart disease, that is, in the presence
      of clinical conditions that are recognized as causing a higher risk of atrial
      arrhythmias. METHODS: Sixty-two patients admitted to the emergency department of
      our institution for a first-ever episode of LAF were enrolled in the study after
      excluding the presence of cardiac or extracardiac conditions known to be
      associated with an increased risk of AF, by medical history, physical
      examination, complete echocardiographic study, and the evaluation of blood
      pressure, thyroid function, urinary catecholamines, serum electrolytes, blood
      glucose, red blood cell count, and arterial blood gases. After cardioversion to
      sinus rhythm by intravenous propafenone, patients were randomized to either
      ramipril 5 mg/day (n = 31) or placebo (n = 31). Holter monitoring and clinical
      examination were performed every 3 months. RESULTS: After a 3-year follow-up, AF
      relapses were observed in 3 patients treated with ramipril and in 10 patients
      allocated to placebo (p < 0.03, Kaplan-Meier, log-rank test). During follow-up,
      none of the patients developed arterial hypertension or other cardiac or
      extracardiac condition known to be associated with increased risk of AF, that is,
      in all patients the diagnosis of LAF was confirmed. CONCLUSIONS: Ramipril is
      effective in preventing relapses of LAF.

PMID- 19118721
TI  - Atrial fibrillation, maybe it is not so lone?

PMID- 19118722
TI  - Safety and efficacy of commercially available ultrasound contrast agents for rest
      and stress echocardiography a multicenter experience.
AB  - OBJECTIVES: The authors sought to define the risks versus benefits of ultrasound
      contrast agents in patients undergoing stress echocardiography. BACKGROUND: The
      Food and Drug Administration recently placed a "black box" warning on the
      ultrasound contrast agents Definity (Bristol-Myers Squibb Medical Imaging,
      Billerica, Massachusetts) and Optison (GE Healthcare, Princeton, New Jersey)
      after their use was temporally related to 4 deaths. The safety of contrast has
      not been systematically evaluated. METHODS: We retrospectively analyzed 42,408
      patients at 3 different institutions who had baseline suboptimal images and/or
      underwent myocardial perfusion imaging and received contrast agents; 18,749 of
      these underwent stress echocardiography. The outcomes (death and myocardial
      infarction [MI]) within 30 min, 24 h, and during long-term follow-up were
      recorded. RESULTS: No deaths or MIs were observed within 30 min; 1 death and 5
      nonfatal MIs were observed within 24 h. This was not different from a matched
      cohort of 15,989 patients not receiving contrast. At 1 h and at 30 days after
      contrast administration, no significant differences in death rates or MIs were
      observed between patients who did and did not receive contrast during their
      stress echocardiogram. Endocardial border visualization in patients with
      suboptimal images resulted in comparable sensitivity (81% vs. 73%, p = NS) and
      diagnostic accuracy (82% vs. 77%, p = NS) for wall motion analysis compared with
      patients with optimal image quality. At long-term follow-up, abnormal wall motion
      and/or myocardial perfusion predicted adverse outcomes (20.6%) when compared with
      patients with normal studies (3.7%). CONCLUSIONS: Despite recent warnings
      regarding echocardiographic contrast, our findings indicate it is a safe and
      useful diagnostic tool in assessment of patients suspected of having coronary
      artery disease.

PMID- 19118723
TI  - Impact of prosthesis-patient mismatch on long-term survival after aortic valve
      replacement: influence of age, obesity, and left ventricular dysfunction.
AB  - OBJECTIVES: This study was designed to evaluate the effect of valve prosthesis
      patient mismatch (PPM) on late survival after aortic valve replacement (AVR) and
      to determine if this effect is modulated by patient age, body mass index (BMI),
      and pre-operative left ventricular (LV) function. BACKGROUND: We recently
      reported that PPM is an independent predictor of operative mortality after AVR,
      particularly when associated with LV dysfunction. METHODS: The indexed valve
      effective orifice area (EOA) was estimated in 2,576 patients having survived AVR
      and was used to define PPM as not clinically significant if it was >0.85
      cm(2)/m(2), as moderate if >0.65 and < or =0.85 cm(2)/m(2), and severe if < or
      =0.65 cm(2)/m(2). RESULTS: After adjustment for other risk factors, severe PPM
      was associated with increased late overall mortality (hazard ratio [HR]: 1.38; p
      = 0.03) and cardiovascular mortality (HR: 1.63; p = 0.0006) in the whole cohort.
      Severe PPM was also associated with increased overall mortality in patients <70
      years old (HR: 1.77; p = 0.002) and in patients with a BMI <30 kg/m(2) (HR: 2.1;
      p = 0.006), but had no impact in older patients or in obese patients. Moderate
      PPM was a predictor of mortality in patients with LV ejection fraction <50% (HR:
      1.21; p = 0.01), but not in patients with preserved LV function. CONCLUSIONS:
      Moderate PPM is associated with increased late mortality in patients with LV
      dysfunction, but with normal prognosis in those with preserved LV function.
      Notwithstanding the previously demonstrated deleterious effect of severe PPM on
      early mortality, this factor appears to increase late mortality only in patients
      <70 years old and/or with a BMI <30 kg/m(2) or an LV ejection fraction <50%.

PMID- 19118724
TI  - Efficacy of cilostazol after endovascular therapy for femoropopliteal artery
      disease in patients with intermittent claudication.
AB  - OBJECTIVES: The purpose of this study was to investigate whether cilostazol
      reduces restenosis and revascularization after endovascular therapy (EVT) for
      femoropopliteal lesions. BACKGROUND: Cilostazol improves walking distance in
      patients with intermittent claudication and reduces restenosis after coronary
      intervention, but its efficacy remains unclear after EVT for femoropopliteal
      disease. METHODS: This study was performed as a multicenter, randomized, open
      label clinical trial. Eighty patients (mean age 70.7 +/- 6.2 years, 84% men) with
      intermittent claudication due to a femoropopliteal lesion were randomly assigned
      to receive or not receive cilostazol in addition to aspirin. The primary end
      point was freedom from target vessel revascularization, and the secondary end
      points were the rate of restenosis and freedom from target lesion
      revascularization and major adverse cardiovascular events, defined as all-cause
      death, myocardial infarction, stroke, repeat revascularization, and leg
      amputation. RESULTS: Clinical follow-up information was obtained in all patients.
      Patient, lesion, and procedural characteristics did not differ significantly
      between the 2 groups. Stenting was performed in 36 patients (cilostazol, 16;
      control, 20; p = 0.36). Freedom from target vessel revascularization at 2 years
      after EVT was significantly higher compared with the control group (84.6% vs.
      62.2%, p = 0.04). The rate of restenosis was lower in the cilostazol group (43.6%
      vs. 70.3%, p = 0.02), and freedom from target lesion revascularization and major
      adverse cardiovascular events was higher in the cilostazol group (87.2% vs.
      67.6%, p = 0.046, 76.8% vs. 45.6%, p = 0.006, respectively). There was no major
      bleeding in either group during follow-up period. CONCLUSIONS: Cilostazol reduced
      restenosis and repeat revascularization after EVT in patients with intermittent
      claudication due to femoropopliteal disease.

PMID- 19118725
TI  - The year in cardiac imaging.

PMID- 19118726
TI  - Lipomatous hypertrophy of interatrial septum combined with thrombus in the region
      of terminal crest of the myocardium.

PMID- 19118728
TI  - Role of mitral valve surgery for secondary mitral regurgitation in heart failure.

PMID- 19118730
TI  - ACCF/ACR/AHA/ASE/ASNC/HRS/NASCI/RSNA/SAIP/SCAI/SCCT/SCMR 2008 Health Policy
      Statement on Structured Reporting in Cardiovascular Imaging.

PMID- 19118731
TI  - ACC/AHA/ACR/ASE/ASNC/HRS/NASCI/RSNA/SAIP/SCAI/SCCT/SCMR/SIR 2008 Key Data
      Elements and Definitions for Cardiac Imaging A Report of the American College of
      Cardiology/American Heart Association Task Force on Clinical Data Standards
      (Writing Committee to Develop Clinical Data Standards for Cardiac Imaging).

PMID- 19118732
TI  - ACCF 2008 Training Statement on Multimodality Noninvasive Cardiovascular Imaging
      A Report of the American College of Cardiology Foundation/American Heart
      Association/American College of Physicians Task Force on Clinical Competence and
      Training Developed in Collaboration With the American Society of
      Echocardiography, the American Society of Nuclear Cardiology, the Society of
      Cardiovascular Computed Tomography, the Society for Cardiovascular Magnetic
      Resonance, and the Society for Vascular Medicine.

PMID- 19118733
TI  - Fit patients with small abdominal aortic aneurysms (AAAs) do not benefit from
      early intervention.
AB  - OBJECTIVES: The UK Small Aneurysm Trial (UKSAT) and the American Aneurysm
      Detection and Management (ADAM) trial both concluded that early elective open
      surgery does not confer any late survival advantage in patients with small
      abdominal aortic aneurysm (AAA) with diameter 4.0 to 5.5 cm. However, two trials
      of endovascular aneurysm repair in small AAA have started based upon speculation
      that a sub-group of particularly fit patients, with low operative mortality, may
      benefit from early intervention. Here we investigate whether the fittest patients
      from the UKSAT might have benefited from early intervention. METHODS: A total of
      1090 patients randomized into the UKSAT between 1991 and 1995 were followed for
      an average of 12 years for mortality. Baseline data were used to calculate the
      Customized Probability Index (CPI), a validated prognostic risk score for
      operative mortality after elective open aneurysm repair that assigns risk points
      for history of cardiac, pulmonary, and renal disease and subtracts risk points
      for use of statins and beta-blockers. Cox regression was used to assess any
      differences in all-cause or aneurysm-related mortality between policies of early
      surgery or surveillance across the fitness spectrum. Tests for interaction used
      CPI scores as a continuous variable but patients also were stratified into
      tertile groups for descriptive purposes. Hazard ratios were adjusted for age,
      gender, and aneurysm diameter. RESULTS: A total of 714 deaths (95 aneurysm
      related) occurred in 8485 person-years (number of patients multiplied by average
      years of conditional follow-up). The mean (standard deviation [SD]) CPI score was
      8.1 (9.9) with similar scores between randomized groups. The tertile groups had
      mean (SD) scores of -1.8 (3.7) for the 389 fittest patients, 8.8 (3.3) for the
      438 moderately fit, 21.4 (6.6) for the 261 least fit with missing scores in 2
      patients. The tests for interaction were non-significant for both all-cause (P =
      .176) and aneurysm-related mortality (.178). However, for the least fit patients
      a survival advantage was seen in the early surgery group; adjusted hazard ratios
      0.73 (95% confidence interval [CI] 0.56-0.96) and 0.46 (95% CI 0.22-0.98) for all
      cause and aneurysm-related mortality respectively. CONCLUSION: Early elective
      surgery did not confer any survival benefit in the fittest patients. On the
      contrary, the possibility of a survival benefit from early intervention in
      patients of poor fitness merits further investigation through meta-analysis or
      validation in other prospective studies.

PMID- 19118736
TI  - Preprocedural neutrophil count predicts outcome in patients with advanced
      peripheral vascular disease undergoing percutaneous transluminal angioplasty.
AB  - BACKGROUND: The neutrophil count has been associated with adverse cardiovascular
      events after percutaneous coronary intervention. There are limited data on risk
      stratification of patients with advanced peripheral vascular disease (PVD) using
      white blood cell (WBC) subtypes. This study assessed the association of total and
      differential WBC counts with adverse outcome in patients with advanced PVD
      undergoing percutaneous transluminal angioplasty (PTA). METHODS: In a
      retrospective cohort study, consecutive de novo procedures were analyzed for
      patients with Rutherford category 4 or 5 PVD who underwent successful
      nonemergency PTA. Cardiovascular risk factors, baseline total and differential
      WBC counts, and angiographic data were recorded. Primary outcome was a composite
      of events of target vessel revascularization (repeat PTA or vascular bypass
      operation) or lower limb amputation. RESULTS: A total of 101 patients were
      studied. Their mean age was 76 +/- 10 years, 54% had diabetes mellitus, 68% were
      hypertensive, and 12% had had previous myocardial infarction. We observed 29
      events during a median period of 14 months (interquartile range, 4-26). Cox
      regression analysis found diabetes mellitus (odds ratio [OR], 4.67; 95%
      confidence interval [CI], 1.35-16.14; P = .02), Rutherford category 5 (OR, 4.18;
      95% CI, 1.06-16.51; P = .04), poor tibial runoff (OR, 4.42; 95% CI, 1.16-16.82; P
      = .03), and preprocedural neutrophil count in the third tertile (OR, 10.77; 95%
      CI, 2.19-52.91; P = .003) were independent predictors of outcome. CONCLUSIONS:
      The results suggest that the preprocedural neutrophil count could be used in
      global risk factor assessment of patients with advanced PVD who are being
      considered for PTA. The neutrophil count may reflect the burden of
      atherosclerosis and tissue damage, and so could identify patients who need more
      aggressive intervention for advanced PVD.

PMID- 19118735
TI  - Risk stratification in critical limb ischemia: derivation and validation of a
      model to predict amputation-free survival using multicenter surgical outcomes
      data.
AB  - BACKGROUND: Patients with critical limb ischemia (CLI) are a heterogeneous
      population with respect to risk for mortality and limb loss, complicating
      clinical decision-making. Endovascular options, compared with bypass, offer a
      tradeoff between reduced procedural risk and inferior durability. Risk stratified
      data predictive of amputation-free survival (AFS) may improve clinical decision
      making and allow for better assessment of new technology in the CLI population.
      METHODS: This was a retrospective analysis of prospectively collected data from
      patients who underwent infrainguinal vein bypass surgery for CLI. Two datasets
      were used: the PREVENT III randomized trial (n = 1404) and a multicenter registry
      (n = 716) from three distinct vascular centers (two academic, one community
      based). The PREVENT III cohort was randomly assigned to a derivation set (n =
      953) and to a validation set (n = 451). The primary endpoint was AFS. Predictors
      of AFS identified on univariate screen (inclusion threshold, P < .20) were
      included in a stepwise selection Cox model. The resulting five significant
      predictors were assigned an integer score to stratify patients into three risk
      groups. The prediction rule was internally validated in the PREVENT III
      validation set and externally validated in the multicenter cohort. RESULTS: The
      estimated 1-year AFS in the derivation, internal validation, and external
      validation sets were 76.3%, 72.5%, and 77.0%, respectively. In the derivation
      set, dialysis (hazard ratio [HR] 2.81, P < .0001), tissue loss (HR 2.22, P
      =.0004), age >or=75 (HR 1.64, P = .001), hematocrit <or=30 (HR 1.61, P = .012),
      and advanced CAD (HR 1.41, P = .021) were significant predictors for AFS in the
      multivariable model. An integer score, derived from the ss coefficients, was used
      to generate three risk categories (low <or= 3 [44.4% of cohort], medium 4-7
      [46.7% of cohort], high >or=8 [8.8% of cohort]). Stratification of the patients,
      in each dataset, according to risk category yielded three significantly different
      Kaplan-Meier estimates for 1-year AFS (86%, 73%, and 45% for low, medium, and
      high risk groups, respectively). For a given risk category, the AFS estimate was
      consistent between the derivation and validation sets. CONCLUSION: Among patients
      selected to undergo surgical bypass for infrainguinal disease, this parsimonious
      risk stratification model reliably identified a category of CLI patients with a
      >50% chance of death or major amputation at 1 year. Calculation of a "PIII risk
      score" may be useful for surgical decision making and for clinical trial designs
      in the CLI population.

PMID- 19118737
TI  - Use of vacuum-assisted closure (VAC) therapy in treating lymphatic complications
      after vascular procedures: new approach for lymphoceles.
AB  - OBJECTIVE: Lymphatic complications, such as lymphocutaneous fistula (LF) and
      lymphocele, are relatively uncommon after vascular procedures, but their
      treatment represents a serious challenge. Vacuum assisted closure (VAC) therapy
      has been reported to be an effective therapeutic option for LF, but the
      effectiveness of VAC therapy for lymphoceles is unclear. METHODS: For LF, we
      apply the VAC directly to the skin defect after extending it to achieve a clean
      wound of at least one inch in length. To treat lymphocele, we convert the
      lymphocele to a LF in a sterile fashion by making a one inch incision in the
      overlying skin and applying the VAC. The setting was a community teaching
      hospital. We used 10 patients that we treated with VAC therapy for LF (n = 4) and
      lymphoceles (n = 6). RESULTS: Duration of in-patient stay, duration of in-patient
      VAC treatment, duration of out-patient VAC treatment, total duration of VAC
      treatment. The median duration of in-patient stay was 4 (range, 0-18) days, the
      median duration of in-patient VAC treatment was 1 (range, 0-5) days, the median
      duration of out-patient VAC treatment was 16 (range, 7-28) days), and the median
      total duration of VAC therapy was 18 (range, 13-29) days. Successful wound
      healing was achieved in all patients with no recurrence after VAC removal. VAC
      therapy for treatment of both LFs and lymphoceles resulted in early control of
      drainage, rapid wound closure, and short hospital stays. CONCLUSION: Our results
      suggest that VAC therapy is a convenient and effective therapeutic option for
      both LFs and lymphoceles.

PMID- 19118739
TI  - Spontaneous re-expansion of a collapsed thoracic endoprosthesis: case report.
AB  - A 43-year-old woman with a type B aortic dissection underwent insertion of a
      Zenith stent graft (Cook Inc, Bloomington, Ind). Chest pain developed 36 hours
      after the procedure. A computed tomography scan showed reopening of the false
      proximal lumen and almost complete device collapse. Because of hemodynamic
      stability and absence of signs of malperfusion, the patient was treated
      conservatively. A control computed tomography scan 7 days later showed full re
      expansion of the endoprosthesis. This case illustrates that in extremely rare
      cases, spontaneous reexpansion of a collapsed thoracic endoprosthesis can occur
      after conservative management.

PMID- 19118738
TI  - Cellular and molecular mechanism regulating blood flow recovery in acute versus
      gradual femoral artery occlusion are distinct in the mouse.
AB  - BACKGROUND: Most current animal models of hindlimb ischemia use acute arterial
      occlusion that does not accurately reflect the pathogenesis of gradual arterial
      occlusion in humans. We, therefore, developed the first mouse model of gradual
      arterial occlusion and tested the hypothesis that the mechanisms regulating blood
      flow recovery are critically dependent on the rate of arterial occlusion.
      METHODS: Gradual arterial occlusion was induced by placing ameroid constrictors
      on the proximal and distal left femoral artery, and ligating the femoral arterial
      branches (n = 36). Acute arterial occlusion was accomplished by excising the left
      femoral artery (n = 36). The blood flow recovery was studied by laser Doppler
      imaging. Differential gene expression between these two models was assessed by
      quantitative real-time polymerase chain reactions (PCR). Inflammatory and
      progenitor cells recruitment were determined by immunohistochemistry. RESULTS: We
      found that hypoxia-related genes increased significantly in the calf, but not in
      the thigh, after gradual and acute femoral arterial occlusion (P < .05). Shear
      stress dependent genes and inflammatory genes were upregulated immediately in the
      thigh only after acute femoral arterial occlusion (P < .05). These differences in
      gene expression were consistent with increased SDF-1alpha expression, recruitment
      of macrophages and hemangiocytes, and higher blood flow recovery after acute
      arterial occlusion than after gradual arterial occlusion (P < .05). CONCLUSION:
      This is the first study to show the mechanisms that regulate blood flow recovery
      are critically dependent on the rate of arterial occlusion. This novel model of
      gradual arterial occlusion may more closely resemble the human diseases, and may
      provide more accurate mechanistic insights for creating novel molecular
      therapies.

PMID- 19118740
TI  - Hypoplasia and fibromuscular dysplasia of infrarenal abdominal aorta with
      downstream aneurysm: case report and review of the literature.
AB  - Fibromuscular dysplasia represents one of the more common types of arterial
      fibrodysplasia, a heterogeneous group of nonatherosclerotic vascular occlusive
      and aneurysmal diseases. This disorder mainly affects renal and cerebral
      arteries, and less frequently, arm, leg, and visceral arteries. Exceptionally, it
      has been described in the abdominal aorta. Aortic hypoplasia is a tubular
      narrowing of a long segment of the aorta and is a rare congenital defect,
      different from coarctation, which is a focal stricture. We present the first
      case, to our knowledge, of an elderly man with infrarenal aortic fibromuscular
      dysplasia associated with aortic hypoplasia, without involvement of renal
      arteries, and contiguous aortoiliac aneurysm.

PMID- 19118741
TI  - A staged replacement of the entire aorta from the ascending arch to the
      hypogastric arteries using a hybrid approach.
AB  - Combined open and endovascular hybrid procedures can be used to treat complex
      aortic pathology. This article reports a five-stage hybrid repair for a complex
      thoracoabdominal aneurysm with dissection in a 57-year-old man. To our knowledge,
      this is the first reported case of replacement and exclusion of the entire native
      human aorta from the root to the iliac bifurcations using a combined open and
      endovascular approach without neurologic complication. Bilateral hypogastric and
      femoral circulation was preserved. Aggressive spinal protective measures,
      including spinal drainage, motor-evoked potentials, and prevention of
      intraoperative and perioperative hypotension, were used during this staged
      approach.

PMID- 19118743
TI  - Reconstruction of occluded thoracic duct for treatment of chylopericardium: a
      novel surgical therapy.
AB  - Chylopericardium is an uncommon disease predominantly caused by trauma. Prolonged
      chyle depletion may result in nutritional, metabolic, and immunologic
      deficiencies due to loss of essential proteins, immunoglobulins, fat, vitamins,
      electrolytes, and water. Medical treatment includes a low-fat diet with medium
      chain triglyceride restriction, cardiac support, diuretic medications, and
      drainage of the pericardial effusion. Conventional surgical therapy consists of
      pericardial fenestration and thoracic duct ligation. We report a case of massive
      secondary chylous pericardial effusion successfully treated with microsurgical
      lymphovenous anastomosis, reconnecting the occluded thoracic duct to the internal
      jugular vein. This case highlights features and management strategies of this
      perplexing clinical condition.

PMID- 19118742
TI  - Endovascular management of a large post-traumatic iliac arteriovenous fistula:
      utilization of a septal occlusion device.
AB  - We describe the management of a large iliac arteriovenous fistula in a 48-year
      old patient presenting with heart failure and pulmonary hypertension. The
      presumptive etiology was a left-lower back stab wound approximately 20 years
      earlier. A large communication between the left internal iliac artery and the
      left internal iliac vein was successfully treated with a septal occlusion device.

PMID- 19118744
TI  - An unusual presentation of pedunculated thrombus in the distal arch of the aorta
      after splenectomy for B-cell lymphoma.

PMID- 19118745
TI  - A modified technique for iliac artery branched endografting using a "tromboned"
      sheath.
AB  - The iliac branched device (IBD) is the only totally endovascular option to
      preserve flow to the internal iliac artery for the treatment of aorto-iliac or
      solitary iliac artery aneurysms. This technique involves the use of two parallel
      guide wires, including the indwelling through-and-through wire and a wire to
      introduce the bridging stent-graft. We describe a technique which uses
      "tromboned" sheaths (ie, a 7F ANL 1 inside a 10F Balkin sheath) for increased
      cross-over stability and avoids problems associated with the use of parallel
      wires inside one sheath. In addition, reduction of the gap between the IBD and
      the origin of the internal iliac artery may result in a more stable position of
      the device.

PMID- 19118746
TI  - Endovascular repair of stent graft collapse by stent-protected angioplasty using
      a femoral-brachial guidewire.
AB  - This report aims to describe an effective endovascular technique to repair a
      stent graft collapse in the distal aortic arch. We report a case of a stent graft
      collapse after off-label endovascular treatment of a traumatic aortic transection
      using a Gore TAG endoprosthesis (oversizing 12%). The collapse was treated by off
      label stent-protected angioplasty (Palmaz stent, Cordis, Miami, Fla) over a stiff
      guidewire, which was passed from the right femoral artery through the collapsed
      stent graft and out at the right brachial artery. We believe that this technique
      enables more precise stent deployment and is safer than the regular guidewire
      position in the ascending aorta.

PMID- 19118747
TI  - The Society for Vascular Surgery--state of the society, 2008.

PMID- 19118748
TI  - Just how far goes DNR?
AB  - Mr T. Ragic presented with a thrombosed limb of an aortobifemoral graft placed
      over 2 decades ago. He has unresectable stage VI lung cancer and do not
      resuscitate (DNR) orders that were suspended during the thrombectomy. A cardiac
      arrest resulted in him being in the intensive care unit a day later ventilator
      dependent and comatose, and repeated computed tomography scans show severe
      cerebral edema. He has frequent ventricular dysrhythmias. His eldest daughter is
      about to deliver his first grandchild, which is the main reason that he requested
      the procedure to extend his life. In discussions with the family, they express
      uncertainty about the implications of his DNR order for current treatment. They
      ask you for your thinking on this matter.

PMID- 19118750
TI  - Regarding "Growth predictors and prognosis of small abdominal aortic aneurysms".

PMID- 19118751
TI  - Regarding "Statins are independently associated with reduced mortality in
      patients undergoing infrainguinal bypass graft surgery for critical limb
      ischemia".

PMID- 19118753
TI  - Carotid artery stenting: a promising therapeutic option for carotid artery
      stenosis or a bubble about to burst?

PMID- 19118755
TI  - Regarding "Easy alternatives to difficult clamping of distal vessels of the leg".

PMID- 19118756
TI  - Regarding "Peroneal artery-only runoff following endovascular revascularization
      is effective for limb salvage in patients with tissue loss".

PMID- 19118758
TI  - Regarding "Side-to-side arteriovenous fistula at the elbow with perforating vein
      ligation".

PMID- 19118759
TI  - Reply.

PMID- 19118763
TI  - A 20-year milestone.

PMID- 19118764
TI  - In the beginning.

PMID- 19118765
TI  - 20 years old and going strong.

PMID- 19118766
TI  - Daytime sleepiness, nighttime sleep quality, stressful life events, and HIV
      related fatigue.
AB  - In this report, the authors describe the relationships between daytime
      sleepiness, nighttime sleep quality, stressful life events, and HIV-related
      fatigue in a sample of 128 individuals; they report the baseline results of a
      longitudinal observational study. They examined sleep using the Pittsburgh Sleep
      Quality Index (a measure of the quality of nighttime sleep), and the Epworth
      Sleepiness Scale, (a measure of daytime sleepiness). Recent stressful life events
      were measured via a methodology developed in a previous 9-year HIV study. Poor
      nighttime sleep was significantly correlated with fatigue intensity (r = .46, p <
      .05), as was daytime sleepiness (r = .20, p < .05). However, in multiple
      regression models, the association between stress and fatigue intensity was not
      explained by daytime sleepiness and was only partially explained by nighttime
      sleep quality. Further research is needed to better elucidate these
      relationships.

PMID- 19118768
TI  - Stigma reported by people living with HIV in south central China.
AB  - This cross-sectional study described the level of stigma reported by people
      living with HIV (PLWH) in south central China and identified factors associated
      with the individuals' perceptions of stigma. The authors carried out face-to-face
      interviews among 322 PLWH. Over half (51%) reported experiencing stigma, 78%
      reported feelings of negative self-worth, 75% reported interpersonal insecurity,
      84% experienced financial problems, and 58% worried about disclosure of their
      disease. High levels of self-perceived stigma were associated with subjects who
      were injection drug users (p = .001), who were less satisfied with responses from
      family members (p = .001), who had disclosed their HIV status widely (p = .001),
      and who reported poorer health status (p = .001). Nurses working with PLWH should
      carry out psychological assessments and care without judgmental attitudes and
      help PLWH disclose their HIV status to family members, which could reduce HIV
      related stigma in the context of Chinese culture.

PMID- 19118769
TI  - Safe sex fatigue, treatment optimism, and serosorting: new challenges to HIV
      prevention among men who have sex with men.
AB  - As the HIV epidemic enters its third decade in the United States, there have been
      few changes in the demographics of the populations most affected by HIV. Twenty
      years of HIV has resulted in changing attitudes toward prevention and infection
      in the population of men who have sex with men (MSM). This article presents a
      review of the recent research regarding HIV risks and attitudes among MSM and
      reports on several trends that have repeatedly emerged from the literature.
      Concepts such as safe sex, treatment optimism, and serosorting have recently
      become common among MSM communities and present a challenge to all who work in
      HIV prevention. Suggestions are made regarding implications for nursing and areas
      for future research.

PMID- 19118767
TI  - HIV stigma and nurse job satisfaction in five African countries.
AB  - This study explored the demographic and social factors, including perceived HIV
      stigma, that influence job satisfaction in nurses from 5 African countries. A
      cross-sectional survey was conducted of nurses (n = 1,384) caring for patients
      living with HIV infection in Lesotho, Malawi, South Africa, Swaziland, and
      Tanzania. Total job satisfaction in this sample was lower than 2 comparable
      studies in South Africa and the United Kingdom. The Personal Satisfaction
      subscale was the highest in this sample, as in the other 2. Job satisfaction
      scores differed significantly among the 5 countries, and these differences were
      consistent across all subscales. A hierarchical regression showed that mental and
      physical health, marital status, education level, urban/rural setting, and
      perceived HIV stigma had significant influence on job satisfaction. Perceived HIV
      stigma was the strongest predictor of job dissatisfaction. These results provide
      new areas for intervention strategies that might enhance the work environment for
      nurses in these countries.

PMID- 19118770
TI  - Changes in transmission risk behaviors across stages of HIV disease among people
      living with HIV.
AB  - Advances in treatments for HIV infection and related opportunistic illnesses have
      significantly extended the life expectancy of people living with HIV. A review of
      the literature on HIV transmission risks among HIV-infected individuals shows
      patterns of risk behavior that vary according to HIV disease stage. Studies
      confirm that the period immediately preceding HIV infection is characterized by
      high rates of risk behaviors, indicating the potential for rapid spread of HIV
      during acute infection. Reductions in risk behavior are often seen immediately
      following an HIV diagnosis. However, these behavioral changes are not universal,
      and an individual's state of health is an important factor relating to
      transmission risks. Chronic periods of asymptomatic HIV infection are generally
      associated with some degree of reverting to risky behaviors. CD4 cell counts
      below 200 cells/mm(3), resulting in a formal diagnosis of AIDS, are associated
      with decreased sexual and drug-related risk behaviors. HIV risk reduction
      interventions for HIV-infected persons, therefore, require tailoring to address
      the health and psychological challenges individuals face as they progress through
      stages of HIV disease. Additional research on both risk behaviors of long-term
      HIV-infected persons and longitudinal data on risk behaviors is needed.

PMID- 19118771
TI  - Factors influencing adherence to antiretroviral therapy for HIV-infected female
      inmates.
AB  - New HIV cases are increasing among women, especially women of color. Moreover,
      the rate of infection for incarcerated women is twice that of incarcerated men.
      With advances in medication therapy, HIV has become a chronic illness that can be
      successfully treated, provided the patient is able to achieve adherence with the
      prescribed antiretroviral medication regimen. Incarcerated women, however,
      frequently come from environments burdened with violence, substance and physical
      abuse, homelessness, child-care issues, and mental illness. Such burdens
      negatively affect the ability of these women to adhere to the medication plan.
      This study explored incarcerated HIV-infected women's barriers to and
      facilitators of adherence to antiretroviral therapy (ART), the role of health
      care provider relationships in adherence, and the ways in which issues of medical
      privacy influence ability or desire to adhere while incarcerated. A secondary
      analysis of an existing set of qualitative interviews with HIV-infected female
      inmates was conducted.

PMID- 19118772
TI  - Sexual behaviors and practices of women living with HIV in relation to pregnancy.
AB  - It has been estimated that 80% of women infected with HIV are of childbearing
      age. Few data exist to describe the sexual behaviors and practices in relation to
      pregnancy and childbearing of women living with HIV. This study is a secondary
      analysis of qualitative data previously gathered to explore the lived experience
      of pregnancy after diagnosis with HIV. Interviews with a purposive sample of 9
      mothers ages 34 to 53 who were previously diagnosed with HIV were tape recorded,
      transcribed, and analyzed to describe sexual behaviors and practices of women
      living with HIV in relation to childbearing. The data showed three themes: (a)
      unprotected sexual relations with the intent to become pregnant, (b) shifting
      responsibility for condom use as the relationship progressed, and (c)
      insufficient knowledge of how to reduce partner transmission risk in relation to
      childbearing. Participants were knowledgeable about the means to minimize
      transmission to the fetus. Consideration of this information may enhance the
      provision of health care to minimize transmission risk and encourage the
      development of further studies about this topic.

PMID- 19118773
TI  - Spiritual well-being and spiritual practices in HIV-infected women: a preliminary
      study.
AB  - Today in the United States, women account for more than one quarter of all HIV
      diagnoses; globally, HIV is the leading cause of death among women ages 35 to 44
      years. There is a growing body of research regarding spirituality among those who
      are infected with HIV. The purposes of this quantitative descriptive study were
      to (a) describe two dimensions of spirituality (spiritual well-being and
      spiritual practices), and (b) determine relationships between these dimensions of
      spirituality in HIV-infected women. Participants were 83 HIV-infected women. The
      average age of the women was 43 years, and the majority of the participants were
      African American (62%). The three most frequently used spiritual practices were
      praying alone, helping others, and listening to music. A high level of spiritual
      well-being was evident among the participants, and a positive relationship was
      shown between spiritual well-being and number of spiritual practices used.
      Recommendations for future research are included.

PMID- 19118774
TI  - A training program for nurses and other health professionals in rural-based
      settings on screening and clinical management of HIV and other sexually
      transmitted infections.
AB  - Populations at risk for HIV and other sexually transmitted infections (STIs)
      include those living in rural areas. The authors describe a statewide training
      program that targeted rural-based health professionals. This program focused on
      HIV, STIs, and viral hepatitis and was designed to (a) enhance participants'
      ability to conduct sexual histories and risk assessments, (b) educate clients
      about risk reduction and prevention, (c) screen for and diagnose these
      infections, (d) clinically manage clients with positive screening test results,
      (e) access prevention and other educational materials, and (f) conduct other
      clinical and public health activities. A total of 122 participants reflecting a
      wide variety of practice settings attended training at five sites throughout
      Minnesota; 74% of participants were nurses and 81% characterized employment
      settings as rural. Nurses and other health professionals in rural settings are an
      important training priority and can play an important role in education,
      prevention, screening, and clinical care for HIV and other STIs.

PMID- 19118775
TI  - Renal cell carcinoma: assessment of key pathologic prognostic parameters and
      patient characteristics in 47,909 cases using the National Cancer Data Base.
AB  - On the basis of the National Cancer Data Base (NCDB), we describe the disease
      characteristics and use of conventional prognostic parameters in a hospital-based
      cohort of pathologically confirmed renal cell carcinomas (RCCs). Between 1993 and
      1998, the NCDB obtained 149 424 cases of kidney (and renal pelvis) cancers from
      registries all over the United States. This database was queried for 47 909
      histologically specified RCCs. Survival outcome was analyzed based on
      conventional clinical and pathologic parameters reported to the database (up to
      2003). Renal cell carcinoma was more common in men (male-female ratio = 1.6:1).
      The mean age was 62.6 years. Most (66.6%) were organ-confined (stage I/II) at the
      time of diagnosis. The mean tumor size was 6.49 cm. The 5-year observed survival
      of RCC was 62.9% for male and 68.1% for female and was 81.0% for younger than 40
      years old and 64.2% for older than 40 years old. The 5-year observed survival of
      RCC patients by the fifth edition 1997 American Joint Committee on Cancer TNM
      staging were stages I, 77.8%; II, 72.8%; III, 55.0%; and IV, 16.9%, demonstrating
      a dramatic decline in patient survival at stage IV. By reported pathologic grade,
      significant stratification was achieved in the observed survival for RCC overall
      irrespective of histologic subtypes (grade 1, 77.8%; 2, 69.6%; 3, 48.8%; and 4,
      35.3% 5-year observed survival). These large NCDB data in RCC confirm the
      importance of pathologic evaluation of traditional prognostic parameters of stage
      and grade in RCC and is a powerful resource in defining cancer patient
      characteristics and analysis of prognostic variables that helps influence future
      cancer care planning and resource allocation.

PMID- 19118776
TI  - Synchronous renal and adrenal masses: an analysis of 80 cases.
AB  - Synchronous renal and adrenal masses are uncommon. Although adrenal masses in the
      context of renal cell carcinoma (RCC) are often suspected as metastasis, other
      adrenal lesions with different therapeutic and prognostic implications may
      coexist with RCC. In a retrospective review of 550 radical nephrectomies with
      ipsilateral adrenalectomy, 80 cases of coexisting renal and adrenal masses were
      identified. The renal masses included 76 RCCs, 3 oncocytomas, and 1 malignant
      pheochromocytoma of adrenal gland involving the kidney. Although the gross
      pathologic impression of adrenal masses in the presence of RCC was metastasis, on
      histologic examination, 56% of them were found to be benign lesions (mostly
      adrenal adenoma/hyperplasia), whereas malignant involvement from RCC was seen in
      43%. The benign and malignant nature of the adrenal lesions in the context of RCC
      could not be discriminated based on the size of adrenal mass. Because of the
      prognostic implication of direct or metastatic involvement of adrenal gland in
      the setting of RCC and the possibility of finding small metastatic foci, a
      meticulous gross and microscopic examination of adrenal glands is emphasized.
      Rare unusual combinations of renal and adrenal lesions such as RCC and adrenal
      histoplasmosis, RCC and adrenal myelolipoma, renal oncocytoma, and adrenal
      pheochromocytoma are also described.

PMID- 19118777
TI  - Epidemiology of bone tumors in Mexico City: retrospective clinicopathologic study
      of 566 patients at a referral institution.
AB  - A retrospective analysis of all bone tumors accessioned at a large referral
      center (Instituto Nacional de Rehabilitacion) in Mexico City between 2000 and
      2005 is presented. A total of 6216 biopsies and surgical resection specimens were
      reviewed during this period, of which 566 corresponded to bone tumors. Benign
      bone tumors accounted for 71.6% of cases and malignant bone tumors for 28.4%. The
      tumors affected men in 53.7% of cases and women in 46.3% of cases, with an
      average age at presentation of 25 years. The femur was the most common location
      of the tumors (39.9%), followed by the tibia (17.7%) and humerus (11.8%). The
      commonest malignant bone tumors were osteosarcoma (46.6%) and chondrosarcoma
      (8.7%). Of malignant bone tumors, 18.6% corresponded to metastases of carcinomas
      from internal organs and 8.1% were multiple myeloma. The most common benign bone
      tumor was osteochondroma (43.7%) followed by giant cell tumor of bone (14.6%) and
      enchondroma (10.1%). The age distribution showed a peak in children and
      adolescents comprised predominantly of benign lesions and a second peak in young
      adults that corresponded to malignant bone tumors (principally osteosarcoma).
      Malignant bone tumors most often involved the femur, vertebra, and tibia. Our
      results parallel the findings previously reported in the world literature and
      show a similar distribution and epidemiology as in other developed and
      underdeveloped countries. Geographic location does not appear to represent a risk
      factor for any particular type of bone tumor and does not affect the age
      distribution, location, or histopathologic type of the lesions.

PMID- 19118778
TI  - Changes in immunoexpression of E-cadherin and beta-catenin in oral squamous cell
      carcinoma with and without nodal metastasis.
AB  - The aim of this study is to analyze the immunohistochemical expression of E
      cadherin and beta-catenin in oral squamous cell carcinoma to better understand
      the biological behavior of this lesion. The sample consisted of 15 cases of the
      tongue and 15 of the lower lip. The pattern and intensity of the labeling and the
      analysis of the percentage of tumor cells immunopositive in membrane for E
      cadherin and beta-catenin were related to the anatomic location of the lesion,
      the presence or absence of nodal metastasis, and the histological gradation of
      malignancy in the tumor invasion front. The presence or absence of cytoplasmic
      and nuclear labeling was also recorded. The membrane expression for E-cadherin
      and beta-catenin predominately displayed a heterogeneous pattern in the
      carcinomas studied. No significant difference was observed between the expression
      pattern and the quantity of cells immunopositive for E-cadherin and beta-catenin
      and the anatomic location of the lesion or the presence or absence of nodal
      metastasis. However, a statistically significant difference was found between the
      reduced expressio?n of these proteins and the high malignancy score. The reduced
      immunoexpression of these proteins in the membrane may be related to the high
      degree of cell indifferentiation in cases of oral squamous cell carcinoma with
      high scores.

PMID- 19118779
TI  - Primary gastrointestinal clear cell sarcoma: report of 2 cases, one case
      associated with IgG4-related sclerosing disease, and review of literature.
AB  - Clear cell sarcoma (CCS) is a distinctive soft tissue sarcoma that shows
      melanocytic differentiation. Primary gastrointestinal (GI) CCSs have been rarely
      reported, but to our knowledge, no association between GI CCSs and immunoglobulin
      G4 (IgG4)-related sclerosing disease has been described in the literature. We
      experienced 2 cases of CCS that arose in the small intestine and metastasized to
      the liver. Histologic features and immunophenotype were typical of CCS. One of
      them showed a unique peritumoral sclerosing inflammatory reaction, which was
      highly reminiscent of IgG4-related sclerosing inflammatory disease. Dense
      lymphoplasmacytic infiltration with extensive sclerosis and obliterative
      phlebitis was observed in the immediate vicinity of the primary and metastatic
      tumors, but not in the distant areas from the tumor. The average number of IgG4
      positive plasma cells was more than 50 per high-power field. We report 2 cases of
      primary GI CCS with one case showing a unique peritumoral IgG4-related
      lymphoplasmacytic sclerosing inflammation.

PMID- 19118780
TI  - Lipomatous supratentorial primitive neuroectodermal tumor with glioblastomatous
      differentiation.
AB  - Cases of cerebral neuroblastoma or supratentorial primitive neuroectodermal tumor
      with malignant gliomatous components are relatively uncommon. Less frequent is
      the combination of these 2 elements with a mesenchymal component. This is a case
      report of a lipomatous supratentorial primitive neuroectodermal tumor with
      glioblastomatous differentiation occurring in a 48-year-old woman. She presented
      with headaches and confusion. A right parietal lobe mass was excised and
      subsequently recurred, requiring additional surgery 10 months later. The patient
      died 13 months after initial surgery. Histologic findings showed a proliferation
      of small rounded synaptophysin-positive neural cells consistent with
      neuroblastoma. These cells were arranged against a benign lipomatous background.
      The second resection consisted primarily of glioblastomatous-like tissue with
      intermixed lipomatous component. The glioblastoma component was marked by
      prominent cellularity, moderate nuclear pleomorphism, readily identifiable
      mitotic activity, vascular proliferative changes, and necrosis. The
      glioblastomatous component of the tumor demonstrated glial fibrillary acidic
      protein immunoreactivity. A Ki-67 labeling index of 18.9% was noted in the
      initial resection. The literature on similar-appearing lesions is reviewed.

PMID- 19118781
TI  - Sinonasal chondromyxoid fibroma.
AB  - Chondromyxoid fibroma (CMF) is a rare benign cartilaginous tumor that usually
      arises from the metaphysis of long bones. In rare cases, however, CMF presents in
      unusual locations, such as the facial bones and sinonasal tract. We present a
      case of a 60-year-old woman with a CMF of the nasal septum. The initial
      radiographic findings were suggestive of a vascular tumor or a malignancy, but
      microscopic examination revealed the typical pathologic features of CMF, and SOX9
      immunostaining confirmed its cartilaginous origin. The tumor was successfully
      excised, and the patient was free of disease at 12-month follow-up. Recognizing
      CMF is important when it presents in unexpected locations, especially because of
      its histologic resemblance to chondrosarcoma. We believe that the use of SOX9 in
      our case assisted in the recognition of the chondroid nature of the lesion and
      facilitated the diagnosis of CMF.

PMID- 19118782
TI  - Mantle cell lymphoma in a tubular adenoma: unusual presentation with synchronous
      colonic carcinoma.
AB  - An 80-year-old man underwent sigmoidectomy for adenocarcinoma. Six months later,
      after a near-syncope incident, pancytopenia was detected in the absence of occult
      blood in the stools. A bone marrow biopsy showed malignant lymphoma, suggestive
      of mantle cell lymphoma (MCL). Colonoscopy at this time revealed 3 colonic
      tubular adenomas. Reassessment of the histology of the colonic polyps and
      appropriate immunohistochemical stains showed that the lamina propria of one of
      the tubular adenomas was infiltrated by MCL. Reexamination of the sections taken
      at the time of the original sigmoidectomy showed MCL in 2 of the regional lymph
      nodes removed at that time, but no evidence of lymphoma in the colon was found.
      To our knowledge, this is the fifth reported case of synchronous occurrence of
      intestinal MCL and colonic carcinoma and the first report of MCL presenting in a
      tubular adenoma of the colon.

PMID- 19118783
TI  - Diffuse ganglioneuromatosis in small intestine associated with neurofibromatosis
      type 1.
AB  - Ganglioneuromatosis of the gastrointestinal tract is a rare condition that has an
      established association with the multiple endocrine neoplasia syndrome, type IIb.
      Its occurrence in neurofibromatosis, in which the large intestine is usually
      affected, is much rarer. We report a case of diffuse ganglioneuromatosis of the
      small bowel, found incidentally during surgery for a malignant peripheral nerve
      sheath tumor arising in the retroperitoneum in a 32-year-old man with
      neurofibromatosis type 1, and review previously reported cases.

PMID- 19118784
TI  - Cerebellar medulloblastoma in the elderly.
AB  - Although medulloblastoma is the most common central nervous system malignancy in
      children, cases are much less common in adults. Moreover, this tumor is
      exceedingly rare in patients older than 65 years. Analysis of previous case
      reports reveals that medulloblastoma in the elderly is more commonly seen in
      males in a lateral location; histologically, medulloblastomas in aged individuals
      usually belong to the classic subtype. During intraoperative consultation, the
      pathologist should consider medulloblastoma in the differential diagnosis of a
      cerebellar mass in the elderly because cytologic features may overlap with
      metastatic small cell carcinoma or lymphoma. We present a case of medulloblastoma
      in a 66-year-old man and review the literature on the subject.

PMID- 19118786
TI  - Surgery for malignant pleural mesothelioma.

PMID- 19118785
TI  - Necrotizing sialometaplasia of the palate associated with angiocentric T-cell
      lymphoma.
AB  - In this article we present 2 cases of necrotizing sialometaplasia (NS) associated
      with angiocentric lymphoma of the midline. Immunohistochemical analysis confirmed
      a T-cell origin, and in situ hybridization in one case revealed its relationship
      to Epstein-Barr virus. These findings suggest that vascular occlusion by the
      neoplastic cells produces ischemia, which leads to local infarction contributing
      to the salivary gland lesion. To our knowledge, the association between
      angiocentric lymphoma and NS has been previously reported in only one instance,
      and we suggest that this particular type of lymphoma should be added to the list
      of related conditions for NS.

PMID- 19118788
TI  - Changes in masseter muscle trigger points following strain-counterstrain or neuro
      muscular technique.
AB  - The aim of this study was to compare the immediate effects, on pressure pain
      sensitivity and active mouth opening, following the application of neuromuscular
      or strain/counter-strain technique in latent myofascial trigger points (MTrPs) in
      the masseter muscle. Seventy-one subjects, 34 men and 37 women, aged 20-65 years
      old, participated in this study. Subjects underwent a screening process to
      establish the presence of MTrPs in the masseter muscle. Subjects were divided
      randomly into three groups: group A which was treated with a neuromuscular
      intervention, group B treated with the strain/counter-strain technique, and group
      C as control group. Each treatment group received a weekly treatment session
      during 3 consecutive weeks. Outcomes measures were pressure pain thresholds
      (PPTs), active mouth opening and local pain (visual analogue scale, VAS) elicited
      by the application of 2.5kg/cm(2) of pressure over the MTrP. They were captured
      at baseline and 1 week after discharge by an assessor blinded to the treatment
      allocation of the subject. The ANOVA found a significant groupxtime interaction
      (F=25.3; p<0.001) for changes in PPT, changes in active mouth opening (F=10.5;
      p<0.001), and local pain evoked by 2.5kg/cm(2) of pressure (F=10.1; p<0.001).
      Within-group effect sizes were large (d>1) for PPT and mouth opening, and
      moderate for local pain (d<0.7, 0.5) in both intervention groups; but small
      (d<0.2) for the control group in all outcomes. No significant differences between
      both intervention groups were found for any outcome (p>0.8). Our results suggest
      that neuromuscular or strain/counter-strain technique might be employed in the
      management of latent MTrPs in the masseter muscle.

PMID- 19118789
TI  - Investigation into the long-term effects of static and PNF stretching exercises
      on range of motion and jump performance.
AB  - The purpose of the present study was to investigate the long-term effects of two
      different stretching techniques on the range of motion (ROM) and on drop jump
      (DJ). DJ scores were assessed by means of a contact mat connected to a digital
      timer. ROM was measured by use of a goniometer. The training was carried out four
      times a week for 6 weeks on 10 subjects as passive static stretching (SS), and on
      9 subjects as contract-relax PNF (CRPNF) stretching. The remaining nine subjects
      did not perform any exercises (control group). One-way Analysis of Variance
      (ANOVA) results indicated that the differences among groups on DJ were not
      statistically different (F(2,27)=.41, p>.05). ROM values were significantly
      higher for both stretching groups, while no change was observed for the control
      group. In conclusion, static and proprioceptive neuromuscular facilitation (PNF)
      stretching techniques improved the ROM, but neither of the stretching exercises
      had any statistically significant effect on the DJ scores.

PMID- 19118790
TI  - The attitudes toward massage (ATOM) scale: reliability, validity, and associated
      findings.
AB  - Despite the key role of attitudes in guiding behavior, no systematic examination
      of attitudes toward massage has been conducted and no standard assessments have
      been created. We developed the attitudes toward massage (ATOM) scale, a nine-item
      measure of an overall attitude toward massage that includes two distinct
      subscales assessing the attitudes of Massage as Healthful and Massage as
      Pleasant. These subscales are reliable (alpha>.70 and >.80, respectively), covary
      with major personality traits and dispositional sensitivities, and are positively
      correlated with broader attitudes toward complementary and alternative medicine.
      Clinical evidence suggests that these attitudes change in response to receiving
      massage, though further research is needed. Supplemental items administered with
      the ATOM illustrate a general preference for female massage therapists while also
      showing this preference to be stronger in men. Attitudes pertaining to massage
      and sexual arousal, which may stand in the way of trying massage for some
      persons, are also examined. With or without the supplemental items, the ATOM
      scale is an easily administered measure for assessing attitudes toward massage
      that can be used in research or practice settings.

PMID- 19118791
TI  - Surface EMG based muscle activity analysis for aerobic cyclist.
AB  - In this study, we determined the muscle activity of aerobic cyclist on biceps
      brachii medial, trapezius medial, latissimus dorsi medial, and erector spinae
      muscles bilaterally during 30 min of cycling. Thirteen male volunteers were
      chosen and placed in two groups (with and without low back pain (LBP)). Surface
      electromyography (sEMG) was recorded bilaterally from selected muscle groups for
      30 min of cycling for each subject. Statistical tests were performed to determine
      the difference in fatigue, using mean power frequency difference. LBP group
      showed a significantly higher fatigue (p<0.05) in left biceps brachii medial when
      compared to the control group. High fatigue in the back muscles in the LBP group
      was not found; however, when linear regression was performed for these
      individuals, the data showed a possibility of worsening in their condition due to
      30 min of cycling.

PMID- 19118792
TI  - The horse as the healer-a study of riding in patients with back pain.
AB  - A total of 24 patients, considerably disabled in daily activities by back pain,
      participated in an Equine Assisted Therapy (EAT) programme. The patients also had
      several health problems in addition to their current pain. The programme
      emphasised the principles of body awareness. The study is aimed at investigating
      not only whether symptom reduction would be achieved, but also at identifying
      qualities of EAT that were particularly beneficial for the patients' well being.
      The study was performed according to action research principles. The treatment
      reduced the pain and lessened other symptoms. The EAT also had an influence on
      the patients' self-image and a positive chain of effects was observed. The
      consequences were described according to four dimensions; the dimension of body
      awareness, competence, emotion and environment. The dimensions were interrelated
      having the simultaneous influence of a transition process and symptom reduction
      towards health.

PMID- 19118793
TI  - Anatomical study of myofascial continuity in the anterior region of the upper
      limb.
AB  - Fifteen unembalmed cadavers were dissected in order to study the "anatomical
      continuity" between the various muscles involved in the movement of flexion of
      the upper limb. This study demonstrated the existence of specific myofascial
      expansions, with a nearly constant pattern, which originate from the flexor
      muscles and extend to the overlying fascia. The clavicular part of the pectoralis
      major sends a myofascial expansion, with a mean length of 3.6cm, to the anterior
      region of the brachial fascia, and the costal part sends one to the medial region
      of the brachial fascia (mean length: 6.8cm). The biceps brachii presents two
      expansions: the lacertus fibrosus, oriented medially, with a mean height of 4.7cm
      and a base of 1.9cm, and a second, less evident, longitudinal expansion (mean
      length: 4.5cm, mean width: 0.7cm). Lastly, the palmaris longus sends an expansion
      to the fascia overlying the thenar muscles (mean length: 1.6cm, mean width:
      0.5cm). During flexion, as these muscles contract, the anterior portion of the
      brachial and antebrachial fascia is subject to tension. As the fascia is rich in
      proprioceptive nerve endings, it is hypothesized that this tension activates a
      specific pattern of receptors, contributing to perception of motor direction. If
      the muscular fascia is in a non-physiological state, these mechanisms are
      altered, and the proprioceptors in the fascia may be incorrectly activated, thus
      giving rise to many types of extra-articular pain.

PMID- 19118794
TI  - Gua sha research and the language of integrative medicine.
AB  - This article is based on research findings published by Nielsen et al. [2007a.
      The effect of 'Gua sha' treatment on the microcirculation of surface tissue: a
      pilot study in healthy subjects. EXPLORE: The Journal of Science and Healing 3,
      456-466]. The abstract was accepted for poster session at the conference on
      fascia (www.fascia2007.com) and appears in the conference text Fascia Research
      [Nielsen, A., Knoblauch, N., Dobos, G., Michalsen, A., Kaptchuk, T., 2007b. The
      effect of 'Gua sha' treatment on the microcirculation of surface tissue: a pilot
      study in healthy subjects. In: Findley, T.W., Schleip, R. (Eds.), Fascia
      Research: Basic Science and Implications for Conventional and Complementary
      Health Care. Elsevier, Munich, Germany, pp. 249-250]. Our Gua sha perfusion
      study, the abstract of which is reprinted in Box 1, was the first investigation
      into the physiology of Gua sha, a technique of traditional East Asian medicine
      used to treat conditions that have features of blood stasis, pain, and/or
      inflammation. Issues raised by our study are discussed here such as the
      significance of the terms used in Western medical literature to describe
      traditional indigenous therapies like Gua sha and the implication of our findings
      not only for future research but toward a shift in how the integrative medical
      community signifies its work.

PMID- 19118795
TI  - Treating patellar tendinopathy with Fascial Manipulation.
AB  - According to Fascial Manipulation theory, patellar tendon pain is often due to
      uncoordinated quadriceps contraction caused by anomalous fascial tension in the
      thigh. Therefore, the focus of treatment is not the patellar tendon itself, but
      involves localizing the cause of this incoordination, considered to be within the
      muscular fascia of the thigh region. Eighteen patients suffering from patellar
      tendon pain were treated with the Fascial Manipulation technique. Pain was
      assessed (in VAS) before (VAS 67.8/100) and after (VAS 26.5/100) treatment, plus
      a follow-up evaluation at 1 month (VAS 17.2/100). Results showed a substantial
      decrease in pain immediately after treatment (p<0.0001) and remained unchanged or
      improved in the short term. The results show that the patellar tendon may be only
      the zone of perceived pain and that interesting results can be obtained by
      treating the muscular fascia of the quadriceps muscle, whose alteration may cause
      motor incoordination and subsequent pathology.

PMID- 19118796
TI  - The 'Bunkie' test: assessing functional strength to restore function through
      fascia manipulation.
AB  - It has been speculated that repetitive patterns of movement will lead to specific
      patterns in fascia contraction, which, if it exceeds a specific limit, will lead
      to injury. Therapists working in the athletic environment are challenged to find
      ways not only to assess and measure fascia dysfunction, but also to restore
      functional strength by manipulating the fascia back to its neutral position. The
      'Bunkie' test was developed over a period of 12 years to measure the function of
      the specific fascia lines in athletes. Numerous athletes from various sports were
      assessed and treated. Results have shown over the years that this test can be
      used successfully to find the cause of and treat injuries and to determine the
      progress of treatment in elite and recreational athletes.

PMID- 19118797
TI  - From journal page to treatment space.

PMID- 19118798
TI  - Yoga techniques as a means of core stability training.
AB  - Core stability in general involves the muscular control required around the
      lumbar spine to maintain functional stability. Stability and movement are
      critically dependent on the coordination of all the muscles surrounding the
      lumbar spine. This paper aims to show that an age-old yoga practice, called
      Uddhyana Bhanda and Nouli, is an effective means of core stability.

PMID- 19118799
TI  - Altered motor control, posture and the Pilates method of exercise prescription.
AB  - The objectives of this study were to compare the effects of three different
      Pilates regimes on chronic, mild low back pain symptoms and to determine whether
      the efficiency of load transfer through the pelvis is improved by those
      exercises. A between subjects equivalent group experimental design was used. The
      independent variable was the type of exercise training (three groups) and the two
      dependent variables were low back pain symptoms and load transfer through the
      pelvis. The outcome measures of the first-dependent variable were a comparison
      between modified Oswestry Disability Questionnaires (one of the standard pain
      instruments) completed pre- and post-program and frequency, intensity and
      duration of low back pain. The outcome measure of the second-dependent variable,
      efficiency of load transfer through the pelvis was the Stork test (one-legged
      standing test) in weight bearing. Although all groups experienced statistically
      significant reductions in frequency, intensity and duration of low back pain
      across the weeks of exercising, there were no significant differences between the
      groups relative to each other.

PMID- 19118800
TI  - Self-management: patient section the new abds.

PMID- 19118801
TI  - In silico modeling system: a national research resource for simulation of complex
      brain disorders.

PMID- 19118802
TI  - Commentary on "In silico modeling system: a national research resource for
      simulation of complex brain disorders".

PMID- 19118803
TI  - Commentary on "In silico modeling system: a national research resource for
      simulation of complex brain disorders".

PMID- 19118804
TI  - Commentary on "In silico modeling system: a national research resource for
      simulation of complex brain disorders." A proposed mathematical and computational
      foundation.

PMID- 19118805
TI  - Activity loss is associated with cognitive decline in age-related macular
      degeneration.
AB  - BACKGROUND/METHODS: The objective of this study was to determine whether
      relinquishing cognitive, physical, and social activities is associated with an
      increased risk of cognitive decline in patients with age-related macular
      degeneration (AMD). We conducted a 3-year longitudinal study of 206 nondemented
      patients with AMD. RESULTS: Twenty-three subjects (14.4%) declined cognitively.
      Age, sex, education, decline in visual acuity, and number of dropped activities
      were associated with cognitive decline; each additional dropped activity
      increased the risk by 58%. Subjects who relinquished three activities were 3.87
      times (95% confidence interval, 1.95-7.76) more likely to become demented than
      subjects who relinquished no activities; those who relinquished five activities
      were 9.54 times (95% confidence interval, 3.05-30.43) more likely. A multivariate
      model demonstrated that number of dropped activities was a powerful predictor of
      cognitive decline after controlling for relevant risk factors, particularly for
      subjects younger than 80 years of age. CONCLUSIONS: Relinquishing valued
      activities is associated with an increased risk of cognitive decline in older
      patients with vision loss caused by AMD. These data suggest the importance of
      promoting optimal cognitive and physical health in patients with AMD and perhaps
      other chronic diseases.

PMID- 19118807
TI  - Physician outpatient contacts and hospitalizations among cognitively impaired
      elderly.
AB  - BACKGROUND: This study examined how physician contacts and hospitalizations vary
      in relation to cognitive function level among community-residing older adults.
      METHODS: Analysis of the 1998 wave of the Health and Retirement Survey (HRS) was
      conducted to create three levels of cognitive function among 6,991 older adults
      by using direct measures for self-respondents and proxy evaluations. Ordinary
      least square regression analyses were used to estimate the probability of
      physician outpatient contacts, number of hospitalizations, and nights
      hospitalized during the last 2 years. RESULTS: Lower cognitive function level was
      found to be associated with decreasing levels of physician contacts and
      increasing levels of hospitalizations as well as nights hospitalized. In
      addition, lower cognitive function levels were consistently related to a variety
      of comorbidities. Moreover, many older adults with low cognitive function levels
      reported or were reported by their proxies as not having a diagnosis of a memory
      related disease (MRD). Finally, having a diagnosis of an MRD was found to be
      associated with more physician contacts but fewer hospital nights compared with
      those who had never received such a diagnosis. CONCLUSIONS: The findings suggest
      the need for increased outreach targeted at identification of community-dwelling
      older adults with decline in cognitive function who are in need of care but are
      underdiagnosed, underutilize physician care, and are overhospitalized.

PMID- 19118808
TI  - Dementia literacy: recognition and beliefs on dementia of the Australian public.
AB  - BACKGROUND: Dementia is a growing health problem worldwide and in Australia.
      Little research has been conducted on dementia literacy in the community.
      METHODS: The aim of this study was to investigate the recognition of dementia and
      beliefs regarding prognosis, cause, and risk reduction in the Australian public.
      A cross-sectional telephone survey of 2,000 randomly selected community-dwelling
      adults (23.4% response rate) was conducted. RESULTS: Eighty-two percent of the
      sample correctly identified "dementia" or "Alzheimer's" from a vignette. There
      were no differences in recognition rates between vignettes describing mild or
      moderate dementia symptoms. Almost half thought that at least partial recovery
      would occur, given appropriate treatment. More than 80% of the sample thought
      that genetics, old age, brain disease, and stroke or mini-stroke contributed to a
      person getting dementia. Seventy-two percent thought that the risk of dementia
      could be reduced. The most frequently suggested methods for risk reduction were
      mental exercise (38.8%), eating healthily (31.0%), physical exercise (30.2%), and
      socializing more (13.9%). Sociodemographic characteristics were associated with
      dementia knowledge and beliefs. CONCLUSIONS: The majority of the Australian
      public recognize the symptoms of dementia and think dementia risk can be reduced.
      However, most do not know of the association between dementia and cardiovascular
      factors. Public awareness campaigns need to increase accurate knowledge of
      factors consistently found to be associated with dementia.

PMID- 19118806
TI  - Amyloid beta peptides in human plasma and tissues and their significance for
      Alzheimer's disease.
AB  - BACKGROUND: We evaluated the amounts of amyloid beta (Abeta)) peptides in the
      central nervous system (CNS) and in reservoirs outside the CNS and their
      potential impact on Abeta plasma levels and Alzheimer's disease (AD) pathology.
      METHODS: Amyloid beta levels were measured in (1) the plasma of AD and
      nondemented (ND) controls in a longitudinal study, (2) the plasma of a cohort of
      AD patients receiving a cholinesterase inhibitor, and (3) the skeletal muscle,
      liver, aorta, platelets, leptomeningeal arteries, and in gray and white matter of
      AD and ND control subjects. RESULTS: Plasma Abeta levels fluctuated over time and
      among individuals, suggesting continuous contributions from brain and peripheral
      tissues and associations with reactive circulating proteins. Arteries with
      atherosclerosis had larger amounts of Abeta40 than disease-free vessels.
      Inactivated platelets contained more Abeta peptides than activated ones.
      Substantially more Abeta was present in liver samples from ND patients. Overall,
      AD brain and skeletal muscle contained increased levels of Abeta. CONCLUSIONS:
      Efforts to use plasma levels of Abeta peptides as AD biomarkers or disease
      staging scales have failed. Peripheral tissues might contribute to both the
      circulating amyloid pool and AD pathology within the brain and its vasculature.
      The wide spread of plasma Abeta values is also due in part to the ability of
      Abeta to bind to a variety of plasma and membrane proteins. Sources outside the
      CNS must be accounted for because pharmacologic interventions to reduce cerebral
      amyloid are assessed by monitoring Abeta plasma levels. Furthermore, the long
      range impact of Abeta immunotherapy on peripheral Abeta sources should also be
      considered.

PMID- 19118809
TI  - Immediate and delayed effects of cognitive interventions in healthy elderly: a
      review of current literature and future directions.
AB  - BACKGROUND: Research on the potential effects of cognitive intervention in
      healthy elderly has been motivated by (1) the apparent effectiveness of cognitive
      rehabilitation in Alzheimer's disease (AD) patients; (2) the face validity of
      bolstering skills eventually burdened by disease; (3) interest in low
      cost/noninvasive methods of preventing or delaying onset of disease; (4) the
      epidemiologic research suggesting protective effects of educational attainment
      and lifelong participation in cognitively stimulating activities; (5) the
      burgeoning industry of brain training products and requisite media attention; and
      (6) the aging world population. METHODS: We performed a systematic review with
      meta-analytic techniques to analyze randomized controlled trials of cognitive
      interventions in healthy elderly. RESULTS: The weighted mean effect size (Cohen's
      d) of cognitive intervention across all outcome measures after training was .16
      (95% confidence interval, .138 to .186). The existing literature is limited by a
      lack of consensus on what constitutes the most effective type of cognitive
      training, insufficient follow-up times, a lack of matched active controls, and
      few outcome measures showing changes in daily functioning, global cognitive
      skills, or progression to early AD. CONCLUSIONS: Our review was limited by a
      small, heterogeneous, and methodologically limited literature. Within this
      literature, we found no evidence that structured cognitive intervention programs
      delay or slow progression to AD in healthy elderly. Further work that accounts
      for the limitations of past efforts and subsequent clear and unbiased reporting
      to the public of the state and progress of research on this topic will help the
      elderly make informed decisions about a range of potential preventive lifestyle
      measures including cognitive intervention.

PMID- 19118810
TI  - French lessons: leadership in Alzheimer's disease.

PMID- 19118811
TI  - The basis for disease-modifying treatments for Alzheimer's disease: the Sixth
      Annual Mild Cognitive Impairment Symposium.
AB  - At the Sixth Annual Mild Cognitive Impairment Symposium in Miami Beach, Florida,
      a multidisciplinary group of experts from the Alzheimer's disease (AD) community
      met to discuss the current status of AD intervention trials and future plans for
      designing trials of prodromal AD and/or mild cognitive impairment. There is no
      agreement regarding a single pathogenic mechanism to be targeted, although a
      consensus seems to be emerging that effective treatment will require attacking
      multiple targets. These targets include beta amyloid (Ass) aggregates (including
      different isoforms and different aggregation species), neurofibrillary tangles
      composed of hyperphosphorylated tau, neuronal and synaptic loss, and mechanisms
      that contribute to Ass deposition-induced inflammation and immune dysregulation.
      Vascular disease, which is very common in the elderly, also appears to be a
      contributor to AD pathogenesis and might be modifiable through pharmacologic and
      lifestyle interventions to reduce the impact of conditions such as hypertension
      and metabolic syndrome. Potential disease-modifying approaches that were
      discussed, including pharmacologic agents that target Abeta, immunotherapy to
      eliminate plaques in the brain, passive immunotherapy, and secretase inhibitors.
      Nonpharmacologic approaches included stimulation of endogenous bone marrow cells,
      which can enter the brain and remove amyloid deposits, and cognitive and exercise
      training. Innovative trial designs are required that will allow a drug's
      effectiveness to be determined efficiently in the transition from normal to mild
      cognitive impairment to probable AD. This might be achieved through the use of
      various forms of imaging and measurement of biochemical markers in the blood or
      cerebrospinal fluid, as well as measures that assess very early cognitive and
      behavioral changes. In the absence of effective treatments for AD, clinicians are
      faced with a dilemma about why, when, and how to disclose the diagnosis to
      patients and their family members and/or caregivers. The issues were discussed
      from multiple perspectives by a panel that included a lay representative,
      neurologist, psychiatrist, primary care physician, and a psychosocial researcher.

PMID- 19118812
TI  - Additional evidence for antagonistic pleiotropic effects of APOE.

PMID- 19118813
TI  - Fine mapping on chromosome 10q22-q23 implicates Neuregulin 3 in schizophrenia.
AB  - Linkage studies have implicated 10q22-q23 as a schizophrenia (SZ) susceptibility
      locus in Ashkenazi Jewish (AJ) and Han Chinese from Taiwan populations. To
      further explore our previous linkage signal in the AJ population (NPL score:
      4.27, empirical p = 2 x 10(-5)), we performed a peakwide association fine mapping
      study by using 1414 SNPs across approximately 12.5 Mb in 10q22-q23. We genotyped
      1515 AJ individuals, including 285 parent-child trios, 173 unrelated cases, and
      487 unrelated controls. We analyzed the binary diagnostic phenotype of SZ and 9
      heritable quantitative traits derived from a principal components factor analysis
      of 73 items from our consensus diagnostic ratings and direct assessment
      interviews. Although no marker withstood multiple test correction for association
      with the binary SZ phenotype, we found strong evidence of association by using
      the "delusion" factor as the quantitative trait at three SNPs (rs10883866,
      rs10748842, and rs6584400) located in a 13 kb interval in intron 1 of Neuregulin
      3 (NRG3). Our best p value from family-based association analysis was 7.26 x 10(
      7). We replicated this association in the collection of 173 unrelated AJ cases (p
      = 1.55 x 10(-2)), with a combined p value of 2.30 x 10(-7). After performing
      10,000 permutations of each of the phenotypes, we estimated the empirical study
      wide significance across all 9 factors (90,000 permutations) to be p = 2.7 x 10(
      3). NRG3 is primarily expressed in the central nervous system and is one of three
      paralogs of NRG1, a gene strongly implicated in SZ. These biological properties
      together with our linkage and association results strongly support NRG3 as a gene
      involved in SZ.

PMID- 19118814
TI  - Genome-wide association study implicates a chromosome 12 risk locus for late
      onset Alzheimer disease.
AB  - Only Apolipoprotein E polymorphisms have been consistently associated with the
      risk of late-onset Alzheimer disease (LOAD), but they represent only a minority
      of the underlying genetic effect. To identify additional LOAD risk loci, we
      performed a genome-wide association study (GWAS) on 492 LOAD cases and 498
      cognitive controls using Illumina's HumanHap550 beadchip. An additional 238 cases
      and 220 controls were used as a validation data set for single-nucleotide
      polymorphisms (SNPs) that met genome-wide significance. To validate additional
      associated SNPs (p < 0.0001) and nominally associated candidate genes, we imputed
      SNPs from our GWAS using a previously published LOAD GWAS(1) and the IMPUTE
      program. Association testing was performed with the Cochran-Armitage trend test
      and logistic regression, and genome-wide significance was determined with the
      False Discovery Rate-Beta Uniform Mixture method. Extensive quality-control
      methods were performed at both the sample and the SNP level. The GWAS confirmed
      the known APOE association and identified association with a 12q13 locus at
      genome-wide significance; the 12q13 locus was confirmed in our validation data
      set. Four additional highly associated signals (1q42, 4q28, 6q14, 19q13) were
      replicated with the use of the imputed data set, and six candidate genes had SNPs
      with nominal association in both the GWAS and the joint imputated data set. These
      results help to further define the genetic architecture of LOAD.

PMID- 19118815
TI  - Infection-triggered familial or recurrent cases of acute necrotizing
      encephalopathy caused by mutations in a component of the nuclear pore, RANBP2.
AB  - Acute necrotizing encephalopathy (ANE) is a rapidly progressive encephalopathy
      that can occur in otherwise healthy children after common viral infections such
      as influenza and parainfluenza. Most ANE is sporadic and nonrecurrent (isolated
      ANE). However, we identified a 7 Mb interval containing a susceptibility locus
      (ANE1) in a family segregating recurrent ANE as an incompletely penetrant,
      autosomal-dominant trait. We now report that all affected individuals and
      obligate carriers in this family are heterozygous for a missense mutation
      (c.1880C-->T, p.Thr585Met) in the gene encoding the nuclear pore protein Ran
      Binding Protein 2 (RANBP2). To determine whether this mutation is the
      susceptibility allele, we screened controls and other patients with ANE who are
      unrelated to the index family. Patients from 9 of 15 additional kindreds with
      familial or recurrent ANE had the identical mutation. It arose de novo in two
      families and independently in several other families. Two other patients with
      familial ANE had different RANBP2 missense mutations that altered conserved
      residues. None of the three RANBP2 missense mutations were found in 19 patients
      with isolated ANE or in unaffected controls. We conclude that missense mutations
      in RANBP2 are susceptibility alleles for familial and recurrent cases of ANE.

PMID- 19118817
TI  - Prevention of falls during stairway descent in older adults.
AB  - A prospective design was applied to examine how older adults would adapt stairway
      intervention stimuli to gait patterns during stairway descent to prevent falls.
      Ambient lighting and an auditory signal were used as stairway intervention
      stimuli. The gait pattern changes with and without stimuli were compared. No
      significant change of angular displacement was found between normal condition and
      intervention conditions under daylight and nightlight. The lighting intervention
      tended to increase the knee's angular velocity for both daylight and nightlight
      conditions, but not the ankle's angular velocity. However, adding the auditory
      signal to the lighting intervention under nightlight condition increased the
      ankle's angular velocity. Under the daylight condition, every intervention was
      significantly helpful to make people step on the floor more confidently compared
      to the condition without interventions. However, the intervention of lighting had
      an opposite effect on the confidence of stepping under the nightlight condition.
      The intervention of lighting may contribute to increase of confidence during
      stair descent while compromising the declined stride length in older adults and
      the potential "rush" factor for falls on stairs.

PMID- 19118816
TI  - Deleterious variants of FIG4, a phosphoinositide phosphatase, in patients with
      ALS.
AB  - Mutations of the lipid phosphatase FIG4 that regulates PI(3,5)P(2) are
      responsible for the recessive peripheral-nerve disorder CMT4J. We now describe
      nonsynonymous variants of FIG4 in 2% (9/473) of patients with amyotrophic lateral
      sclerosis (ALS) and primary lateral sclerosis (PLS). Heterozygosity for a
      deleterious allele of FIG4 appears to be a risk factor for ALS and PLS, extending
      the list of known ALS genes and increasing the clinical spectrum of FIG4-related
      diseases.

PMID- 19118818
TI  - Is control a viable goal in the treatment of pathological gambling?
AB  - According to a report of National Gambling Impact Study Commission (National
      Gambling Impact Study Commission (1999). Final report. Washington, DC: Government
      Printing Office.), 97% of problem gamblers in the United States do not seek
      treatment. Within the small proportion of problem gamblers who enter into
      treatment, a high percentage drops out. Despite the fact that some researchers
      argue against abstinence as the only acceptable treatment goal and that regaining
      control over gambling behaviour appears to be possible for some pathological
      gamblers (PG), abstinence has been the only gambling intervention treatment goal.
      The primary goal of this study was to verify whether controlled gambling is a
      viable goal for pathological gamblers. The second goal was to identify the
      characteristics that predicted a successful outcome for treatment with a
      controlled gambling goal. Eighty-nine PGs were enrolled in cognitive-behavioural
      treatment aimed at controlled gambling. Six and twelve month follow-ups were
      conducted in order to evaluate the maintenance of therapeutic gains and to
      identify significant predictors of successful controlled gambling. Results showed
      that using the intent-to-treat procedure, 63% had a score of 4 or less on the DSM
      IV at the end of treatment. That proportion was 56% and 51% at the 6- and 12
      month follow-ups. If we retain only those who completed the treatment, these
      proportions increased to 92%, 80% and 71% at post-treatment, 6- and 12-month
      follow-ups, respectively. On the majority of the measures, significant
      improvements were found at post-treatment and the therapeutic gains were
      maintained at the 6- and 12-month follow-ups. However, few variables were
      identified to predict who would benefit from control rather than abstinence. The
      clinical and philosophical implications of these results are discussed in this
      paper.

PMID- 19118819
TI  - The GAB2 gene and the risk of Alzheimer's disease: replication and meta-analysis.
AB  - BACKGROUND: Recently, GAB2 has been suggested to modify the risk of late-onset
      Alzheimer's disease (AD) among APOEepsilon4 carriers. However, replication data
      are inconsistent. METHODS: In a population-based cohort study (n = 5507; age >
      55) with 443 incident AD cases, we investigated the association between rs4945261
      and AD. Because we used high-density genotyping, we also investigated other
      polymorphisms within and around GAB2 and performed a meta-analysis with published
      studies. RESULTS: We found that rs4945261 was associated with AD among
      APOEepsilon4 carriers (p = .02) but not among noncarriers (p = .26). Fifteen of
      the 20 remaining polymorphisms within GAB2 and several polymorphisms in the
      250kbp-region surrounding GAB2 were also associated with AD among carriers and
      only one among noncarriers. For rs2373115, meta-analysis yielded an odds ratio of
      1.58 (1.17-2.14) with p = 3.0 * 10(-3) among carriers and 1.09 (.97-1.23) with p
      = .16 among noncarriers. For rs4945261, the pooled odds ratio was 1.75 (1.21
      2.55) with p = 3.0 * 10(-3) among carriers and 1.20 (1.01-1.41) with p = .03
      among noncarriers. CONCLUSIONS: We found GAB2 to be associated with AD.
      Furthermore, the meta-analysis also suggests that GAB2 modifies the risk of AD in
      APOEepsilon4 carriers.

PMID- 19118820
TI  - Depressive symptoms are associated with soluble P-selectin reactivity to acute
      exercise in heart failure.
AB  - BACKGROUND: To determine the effects of depressive symptom severity on the
      circulating soluble adhesion molecule response to an acute exercise challenge in
      patients with heart failure (HF) compared with control subjects. METHODS: Thirty
      eight male HF patients and 19 male control subjects (mean age +/- SEM: 55.5 +/-
      1.9) completed the Beck Depression Inventory (BDI) before undergoing a moderate
      20-minute bicycle exercise at approximately 65% to 70% VO(2peak). Plasma levels
      of the soluble adhesion molecules P-selectin (sP-selectin) (sCD62P) and soluble
      intercellular adhesion molecule-1 (sICAM-1) were determined immediately before
      and after and 10 minutes after exercise. RESULTS: Higher BDI scores moderated
      greater increases in sP-selectin levels in response to exercise over time in HF
      patients as compared with control subjects [F(1.8/84.5) = 3.25, p = .05]. Post
      hoc testing revealed that in HF patients, but not in control subjects, higher BDI
      scores were significantly associated with greater increases in sP-selectin levels
      over time in response to exercise [BDI by exercise interaction: F(1.6/49.6) =
      5.67, p = .010]. Also, in HF patients, but not in control subjects, higher BDI
      scores were associated with higher sP-selectin levels at pre-exercise and
      postexercise time points [main effect BDI: F(1/31) = 4.86, p = .035].
      CONCLUSIONS: Our findings suggest that in male HF patients with increasing
      depressive symptom severity, levels of the adhesion molecule sP-selectin are
      higher before and after exercise and have greater increases in response to
      exercise. This could have implications for acute coronary syndromes associated
      with exercise and thereby may impact mortality.

PMID- 19118822
TI  - Regioselective synthesis of a glycomimetic trisaccharide of Sialyl Lewis (sLex).
AB  - Sialyl Lewis (sLe(x)) is the smallest naturally occurring carbohydrate ligand
      that binds to E-Selectin on the activated endothelium. We report here the total
      synthesis of acetic acid-sLe(x) analog (12), for testing as a therapeutic agent.
      Methoxyethyl 4-O-(3,4-O-isopropylidene-beta-D-galactopyranosyl)-beta-D
      glucopyranoside (3) was prepared starting from the methoxyethyl-beta-D-lactoside
      (2), which was selectively benzoylated to give the methoxyethyl 2,6-di-O-benzoyl
      4-O-(2,6-di-O-benzoyl-3,4-O-isopropylidene-beta-D-galactopyranosyl)-beta-D
      glucopyranoside (4). Glycosylation of acceptor 4 with methyl 2,3,4-tri-O-benzyl-1
      thio-beta-L-fucopyranoside (5) in the presence of cupric bromide and
      tetrabutylammonium bromide afforded the corresponding methoxyethyl 2,6-di-O
      benzyl-3-O-(2,3,4-tri-O-benzyl-alpha-L-fucopyranosyl)-4-O-(2,6-di-O-benzyl-3,4-O
      isopropylidene-beta-D-galactopyranosyl)-beta-D-glucopyranoside (6). Selective
      removal of the 4'',6''-O-isopropylidene group from 6 gave the deprotected
      trisaccharide 7. The regioselective esterification of O-3'' of trisaccharide 8
      (obtained from the dibutylstannylene derivative of 7) with benzyl-2-bromoacetate
      and tetrabutylammonium bromide afforded the 3''-O-carbobenzyloxymethyl
      trisaccharide derivative 9, which on saponification and hydrogenolysis with
      palladium-charcoal afforded the target trisaccharide 12 glycomimetic of Sialyl
      Lewis (sLe(x)) trisaccharide omitting the sialic acid moiety.

PMID- 19118823
TI  - Categorizing moving objects into film genres: the effect of animacy attribution,
      emotional response, and the deviation from non-fiction.
AB  - The reported study follows the footsteps of Heider, and Simmel (1944) [Heider,
      F., & Simmel, M. (1944). An experimental study of apparent behavior. American
      Journal of Psychology, 57, 243-249] and Michotte (1946/1963) [Michotte, A.
      (1963). The perception of causality (T.R. Miles & E. Miles, Trans.). London:
      Methuen (Original work published 1946)] who demonstrated the role of object
      movement in attributions of life-likeness to figures. It goes one step further in
      studying the categorization of film scenes as to genre as a function of object
      movements. In an animated film scene portraying a chase, movements of the chasing
      object were systematically varied as to parameters: velocity, efficiency,
      fluency, detail, and deformation. The object movements were categorized by
      viewers into genres: non-fiction, comedy, drama, and action. Besides this
      categorization, viewers rated their animacy attribution and emotional response.
      Results showed that non-expert viewers were consistent in categorizing the genres
      according to object movement parameters. The size of its deviation from the
      unmanipulated movement scene determined the assignment of any target scene to one
      of the fiction genres: small and moderate deviations resulted in categorization
      as drama and action, and large deviations as comedy. The results suggest that
      genre classification is achieved by, at least, three distinct cognitive
      processes: (a) animacy attribution, which influences the fiction versus non
      fiction classification; (b) emotional responses, which influences the
      classification of a specific fiction genre; and (c) the amount of deviation from
      reality, at least with regard to movements.

PMID- 19118824
TI  - Does history repeat itself? Cortical columns 3. A cortex of columns.

PMID- 19118821
TI  - Strain specific synaptic modifications on ventral tegmental area dopamine neurons
      after ethanol exposure.
AB  - BACKGROUND: Genetic factors and previous alcohol experience influence alcohol
      consumption in both humans and rodents. Specifically, a prior experience with
      ethanol increases ethanol intake in both ethanol-preferring C57BL/6 (C57) and
      ethanol non-preferring DBA/2 (DBA) mice. Whereas the ventral tegmental area (VTA)
      importantly regulates dopamine levels and ethanol intake, it is unknown whether
      ethanol experience differentially alters synaptic properties of VTA dopamine
      neurons in ethanol-preferring and non-preferring mice. METHODS: The properties of
      excitatory and inhibitory inputs and the ability to elicit long-term potentiation
      (LTP) were assessed with whole-cell patch-clamp recordings in VTA dopamine
      neurons from C57 and DBA mice 24 hours after a single ethanol (2 g/kg, IP) or
      equivalent saline injection. RESULTS: Ethanol exposure increased gamma
      aminobutyric acid (GABA) release onto VTA dopamine neurons in DBA mice, as
      previously observed in C57 mice. However, a single ethanol exposure reduced alpha
      amino-3-hydroxy-5-methylisoxazole-4-propionic acid receptor (AMPAR) and N-methyl
      D-aspartate receptor (NMDAR) function and LTP in VTA dopamine neurons from DBA
      but not C57 mice. CONCLUSIONS: A single ethanol exposure selectively reduced
      glutamate receptor function in VTA dopamine neurons from the ethanol non
      preferring DBA strain but enhanced GABA signaling in both C57 and DBA strains.
      These results support the notion that VTA dopamine neurons are a central target
      of ethanol-induced neural plasticity, which could contribute to ethanol
      consumption. Furthermore, these findings highlight the possible need for
      specialized therapeutic interventions for alcoholism based on individual
      intrinsic differences.

PMID- 19118825
TI  - Changes in serum cortisol and prolactin associated with acupuncture during
      controlled ovarian hyperstimulation in women undergoing in vitro fertilization
      embryo transfer treatment.
AB  - OBJECTIVE: To determine whether changes in serum cortisol (CORT) and PRL are
      affected by acupuncture (Ac) in Ac-treated IVF patients. DESIGN: Prospective
      cohort clinical study. SETTING: Private practice reproductive endocrinology and
      infertility clinic and private practice acupuncture consortium. PATIENT(S): Sixty
      seven reproductive-age infertile women undergoing IVF. INTERVENTION(S): Blood
      samples were obtained from all consenting new infertility patients and serum CORT
      and serum PRL were obtained prospectively. Patients were grouped as controls (IVF
      with no Ac) and treated (IVF with Ac) according to acupuncture protocols derived
      from randomized controlled trials. MAIN OUTCOME MEASURE(S): Serum levels of CORT
      and PRL were measured and synchronized with medication stimulation days of the
      IVF cycle (e.g., day 2 of stimulation, day 3, etc.). Reproductive outcomes were
      collected according to Society for Assisted Reproductive Technology protocols,
      and results were compared between controls and those patients treated with Ac.
      RESULT(S): CORT levels in Ac group were significantly higher on IVF medication
      days 7, 8, 9, 11, 12, and 13 compared with controls. PRL levels in the Ac group
      were significantly higher on IVF medication days 5, 6, 7, and 8 compared with
      controls. CONCLUSION(S): In this study, there appears to be a beneficial
      regulation of CORT and PRL in the Ac group during the medication phase of the IVF
      treatment with a trend toward more normal fertile cycle dynamics.

PMID- 19118826
TI  - Risk factors for psychiatric disorders in infertile women and men undergoing in
      vitro fertilization treatment.
AB  - OBJECTIVE: To identify risk factors associated with depression and anxiety in
      infertile women and men undergoing in vitro fertilization (IVF). DESIGN:
      Prospective study. SETTING: A university hospital in Sweden during a 2-year
      period. PATIENT(S): 825 participants (413 women and 412 men). INTERVENTION(S):
      Primary Care Evaluation of Mental Disorders (PRIME-MD), based on the Diagnostic
      and Statistical Manual of Mental Disorders, 4th edition (DSM-IV), as the
      diagnostic tool for evaluating mood and anxiety disorders, and fertility history
      and outcome of IVF treatment collected from the patients' medical records. MAIN
      OUTCOME MEASURE(S): Risk factors associated with depression and anxiety
      disorders. RESULT(S): A negative pregnancy test and obesity were the independent
      risk factors for any mood disorders in women. Among men, the only independent
      risk factor for depression was unexplained infertility. No IVF-related risk
      factors could be identified for any anxiety disorder. CONCLUSION(S): A negative
      pregnancy test is associated with an increased risk for depression in women
      undergoing IVF, but no risk of developing anxiety disorders is associated with
      the pregnancy test result after IVF. Pregnancy test results were not a risk
      factor for depression or anxiety among men.

PMID- 19118828
TI  - Biopsychosocial factors are associated with low back pain in female nursing
      students: a cross-sectional study.
AB  - BACKGROUND: Occupational low back pain is a significant problem among nurses.
      Recent literature suggests current occupational preventative strategies for
      nurses have not been effective. Given low back pain is already prevalent before
      commencing employment, nursing students should be the target of preventative
      interventions. Modifiable personal factors which contribute to low back pain have
      proven difficult to identify, but are thought to play an important role in the
      biopsychosocial nature of low back pain. OBJECTIVES: To evaluate the contribution
      of personal biopsychosocial factors to low back pain in nursing students. DESIGN:
      Cross-sectional study comprising physical testing and questionnaires. SETTINGS:
      Two university undergraduate nursing schools in Western Australia. PARTICIPANTS:
      170 female undergraduate nursing students. METHODS: Low back pain and control
      subjects were compared across social, lifestyle (physical activity),
      psychological (stress, anxiety, depression, back pain beliefs, coping strategies
      and catastrophising) and physical (spinal postures and spinal kinematics in
      functional tasks, leg and back muscle endurance, spinal repositioning error and
      cardiovascular fitness) characteristics. Low back pain was considered as either
      "minor" or "significant" depending upon pain severity, duration, impact and level
      of disability. RESULTS: Over 30% of all subjects (mean age 22.5+/-4.5 years)
      reported "significant" low back pain in the preceding 12 months. Univariate
      analysis: social measures did not distinguish between groups. Subjects with
      "significant" low back pain were more physically active (p=0.04), had higher
      stress scores (p=0.01) and used passive coping strategies (p<0.001) more than
      other subjects. "Significant" low back pain subjects held their lower lumbar
      spine in a more extended posture during transfers at bed height than other
      subjects. No differences between groups were found for sagittal spinal mobility,
      static spinal posture, muscle endurance, spinal repositioning error,
      cardiovascular fitness or other psychological measures. Multivariate analysis:
      regression analysis revealed stress, coping, physical activity, spinal
      kinematics, and age all contributed independently to the presence of low back
      pain, representing a significant 23% of variance. CONCLUSIONS: Modifiable
      lifestyle, psychological and physical factors were independently associated with
      low back pain in nursing students. Targeting personal factors associated with low
      back pain in nursing students, rather than occupational factors in working nurses
      may help improve the impact of low back pain in nurses. Prospective studies are
      required to confirm the relevance of these findings for risk of future low back
      pain in nurses.

PMID- 19118829
TI  - The calcimimetic R-568 retards uremia-enhanced vascular calcification and
      atherosclerosis in apolipoprotein E deficient (apoE-/-) mice.
AB  - OBJECTIVE: Secondary hyperparathyroidism of chronic kidney disease promotes
      vascular calcification. Calcimimetics reduce serum parathyroid hormone, calcium
      (Ca), and phosphorus by calcium-sensing receptor (CaR) activation. Here we
      examined possible effects of the calcimimetic R-568 (R-568) on the progression of
      aortic calcification and atherosclerosis in apoE(-/-) mice with chronic renal
      failure (CRF) and the potential implication of aortic smooth muscle cell CaR.
      METHODS AND RESULTS: ApoE(-/-) mice were assigned to 3 CRF groups and 1 non-CRF
      group receiving daily gavage with R-568, calcitriol, or vehicle. Serum Ca and
      phosphorus and parathyroid gland volume of CRF mice were decreased by R-568,
      whereas elevated serum FGF23 and total cholesterol remained unchanged. Both
      aortic plaque and non-plaque calcification was lower in R-568 mice, and so was
      atherosclerotic plaque area fraction. In vitro, R-568 induced a decrease in
      smooth muscle cell calcification when cultured in high phosphate medium. This
      decrease was abolished in CaR-SiRNA-transfected cells. CONCLUSIONS: The
      calcimimetic R-568 delayed the progression of both aortic calcification and
      atherosclerosis in uremic apoE(-/-) mice. This effect was mediated via a better
      control of hyperparathyroidism including serum Ca and phosphorus. Direct vascular
      CaR activation also could have played a role in the observed effects.

PMID- 19118830
TI  - Visceral adipose tissue, adiponectin levels and insulin resistance are related to
      atherosclerosis as assessed by whole-body magnetic resonance angiography in an
      elderly population.
AB  - OBJECTIVE: The principal aim of this study was to determine whether the amount of
      visceral adipose tissue (VAT) is more related than subcutaneous adipose tissue
      (SAT) to atherosclerosis assessed by whole-body MRA (WBMRA). A further objective
      was to investigate whether traditional risk factors, inflammation, or adipokines
      could explain the hypothesized relationship between VAT and atherosclerosis.
      METHODS: Men and women aged 70 were recruited from the general population into
      the Prospective Investigation of The Vasculature in Uppsala Seniors (PIVUS) and
      306 of them underwent WBMRA in a clinical 1.5-T scanner. The arterial tree was
      assessed for degree of stenosis or occlusion and a total atherosclerotic score
      (TAS) was established. Information on risk factors and BMI and on SAT and VAT,
      segmented on an axial MR scan was collected. Adiponectin, leptin, and high
      sensitive C-reactive protein (hsCRP) were measured in serum. HOMA index was used
      as a marker of insulin resistance. RESULTS: VAT was related to TAS independently
      of gender, total obesity (BMI), amount of SAT, hsCRP and also to the traditional
      risk factors included in the Framingham risk score (FRS) in an elderly
      population. Adiponectin or the HOMA insulin resistance, but not leptin or VAT,
      together with FRS was significantly related to TAS in a multiple censored
      regression model. CONCLUSION: Adiponectin attenuated the relationship between VAT
      and TAS, suggesting that adiponectin and insulin resistance is an important link
      between visceral adiposity and atherosclerosis.

PMID- 19118831
TI  - Validation of subject-specific automated p-FE analysis of the proximal femur.
AB  - BACKGROUND: The use of subject-specific finite element (FE) models in clinical
      practice requires a high level of automation and validation. In Yosibash et al.
      [2007a. Reliable simulations of the human proximal femur by high-order finite
      element analysis validated by experimental observations. J. Biomechanics 40, 3688
      3699] a novel method for generating high-order finite element (p-FE) models from
      CT scans was presented and validated by experimental observations on two fresh
      frozen femurs (harvested from a 30 year old male and 21 year old female). Herein,
      we substantiate the validation process by enlarging the experimental database (54
      year old female femur), improving the method and examine its robustness under
      different CT scan conditions. APPROACH: A fresh frozen femur of a 54 year old
      female was scanned under two different environments: in air and immersed in water
      (dry and wet CT). Thereafter, the proximal femur was quasi-statically loaded in
      vitro by a 1000N load. The two QCT scans were manipulated to generate p-FE models
      that mimic the experimental conditions. We compared p-FE displacements and
      strains of the wet CT model to the dry CT model and to the experimental results.
      In addition, the material assignment strategy was reinvestigated. The
      inhomogeneous Young's modulus was represented in the FE model using two different
      methods, directly extracted from the CT data and using continuous spatial
      functions as in Yosibash et al. [2007a. Reliable simulations of the human
      proximal femur by high-order finite element analysis validated by experimental
      observations. J. Biomechanics 40, 3688-3699]. RESULTS: Excellent agreement
      between dry and wet FE models was found for both displacements and strains, i.e.
      the method is insensitive to CT conditions and may be used in vivo. Good
      agreement was also found between FE results and experimental observations. The
      spatial functions representing Young's modulus are local and do not influence
      strains and displacements prediction. Finally, the p-FE results of all three
      fresh frozen human femurs compare very well to experimental observations
      exemplifying that the presented method may be in a mature stage to be used in
      clinical computer-aided decision making.

PMID- 19118832
TI  - Fingerprinting and source identification of an oil spill in China Bohai Sea by
      gas chromatography-flame ionization detection and gas chromatography-mass
      spectrometry coupled with multi-statistical analyses.
AB  - This paper describes a case study in which advanced chemical fingerprinting and
      data interpretation techniques were used to characterize the chemical composition
      and determine the source of an unknown spilled oil reported on the beach of China
      Bohai Sea in 2005. The spilled oil was suspected to be released from nearby
      platforms. In response to this specific site investigation need, a tiered
      analytical approach using gas chromatography-mass spectrometry (GC-MS) and gas
      chromatography-flame ionization detection (GC-FID) was applied. A variety of
      diagnostic ratios of "source-specific marker" compounds, in particular isomers of
      biomarkers, were determined and compared. Several statistical data correlation
      analysis methods were applied, including clustering analysis and Student's t-test
      method. The comparison of the two methods was conducted. The comprehensive
      analysis results reveal the following: (1) The oil fingerprinting of three
      spilled oil samples (S1, S2 and S3) positively match each other; (2) The three
      spilled oil samples have suffered different weathering, dominated by evaporation
      with decrease of the low-molecular-mass n-alkanes at different degrees; (3) The
      oil fingerprinting profiles of the three spilled oil samples are positive match
      with that of the suspected source oil samples C41, C42, C43, C44 and C45; (4)
      There are significant differences in the oil fingerprinting profiles between the
      three spilled oil samples and the suspected source oil samples A1, B1, B2, B3,
      B4, C1, C2, C3, C5 and C6.

PMID- 19118833
TI  - Determination of four heterocyclic insecticides by ionic liquid dispersive liquid
      liquid microextraction in water samples.
AB  - A novel microextraction method termed ionic liquid dispersive liquid-liquid
      microextraction (IL-DLLME) combining high-performance liquid chromatography with
      diode array detection (HPLC-DAD) was developed for the determination of
      insecticides in water samples. Four heterocyclic insecticides (fipronil,
      chlorfenapyr, buprofezin, and hexythiazox) were selected as the model compounds
      for validating this new method. This technique combines extraction and
      concentration of the analytes into one step, and the ionic liquid was used
      instead of a volatile organic solvent as the extraction solvent. Several
      important parameters influencing the IL-DLLME extraction efficiency such as the
      volume of extraction solvent, the type and volume of disperser solvent,
      extraction time, centrifugation time, salt effect as well as acid addition were
      investigated. Under the optimized conditions, good enrichment factors (209-276)
      and accepted recoveries (79-110%) were obtained for the extraction of the target
      analytes in water samples. The calibration curves were linear with correlation
      coefficient ranged from 0.9947 to 0.9973 in the concentration level of 2-100
      microg/L, and the relative standard deviations (RSDs, n=5) were 4.5-10.7%. The
      limits of detection for the four insecticides were 0.53-1.28 microg/L at a signal
      to-noise ratio (S/N) of 3.

PMID- 19118834
TI  - Comparison of electrospray ionization, atmospheric pressure chemical ionization
      and atmospheric pressure photoionization for determining estrogenic chemicals in
      water by liquid chromatography tandem mass spectrometry with chemical
      derivatizations.
AB  - This study compared the sensitivities and matrix effects of four ionization modes
      and four reversed-phase liquid chromatographic (LC) systems on analyzing estrone
      (E1), 17beta-estradiol (E2), estriol (E3), 17alpha-ethinylestradiol (EE2), 4
      nonylphenol (NP), 4-tert-octylphenol (OP), bisphenol A (BPA) and their
      derivatives of dansyl chloride or pentafluorobenzyl bromide (PFBBr) in water
      matrixes using a triple-quadrupole mass spectrometer with selected reaction
      monitoring (SRM). The four probes were electrospray ionization (ESI), atmospheric
      pressure chemical ionization (APCI), atmospheric pressure photoionization (APPI)
      and APCI/APPI; the four LC systems were ultra-performance liquid chromatography
      (UPLC) with or without post-column split, a mixed-mode column and two-dimensional
      LC (2D-LC). Dansylated compounds with ESI at UPLC condition had the most intense
      signals and less matrix effects of the various combinations of ionization and LC
      systems. The on-column limits of detection (LODs) of dansylated estrogens by SRM
      were 0.05-0.20 pg, and the LODs in sewage treatment plant effluent and in river
      water were 0.23-0.52 and 0.56-0.91 ng/L, respectively. The LODs using selected
      ion monitoring (SIM) reached low ng/L levels in real samples and measured
      concentrations were comparable with those of SRM.

PMID- 19118835
TI  - Limits of separation of a multi-capillary column with mixtures of volatile
      organic compounds for a flame ionization detector and a differential mobility
      detector.
AB  - The resolving power of a multi-capillary column (MCC) was evaluated using 14
      mixtures of volatile organic compounds with known composition and complexity
      which was incremented stepwise up to 129 constituents. The number of constituents
      in these mixtures versus the number of components separated and detected with a
      flame ionization detector showed a proportional rise, with a decreasing slope, to
      76 peaks after which a plateau was reached. This was improved 23.7% to 94
      constituents, or 73% of all compounds in the mixture, after simplex optimization
      of carrier gas linear velocity, initial temperature and program rate. When the
      detection method was differential mobility spectrometry (DMS), additional
      selectivity was introduced through ion formation and separation. Fifty nine
      compounds were detected by DMS and 46 were separated by retention time; 13 were
      co-eluted and 7 of these were resolved by differential ion mobility (90% of all
      components ionized). A correlation of -0.412 between retention time for gas
      chromatography (GC) and differential mobility for DMS suggested a significant
      level of orthogonal character and the method of GC-DMS should not be seen as
      sequential only.

PMID- 19118836
TI  - Versatile method for electroosmotic flow measurements in microchip
      electrophoresis.
AB  - A novel versatile method for the determination of low or high electroosmotic
      mobility values in microdevices of variable microchannel design is presented. The
      electroosmotic flow (EOF) calculation is based on the difference between the
      apparent and effective mobilities of a reference compound. The proposed method
      uses microchip frontal electrophoresis for the determination of these mobilities.
      This requires simple monochannel microchip design and demonstrates versatile and
      time-saving procedure when compared to conventional current monitoring method
      when measuring low EOF. It has been applied successfully to the characterization
      of different coating procedure in glass and poly(dimethylsiloxane) microchips.

PMID- 19118837
TI  - C18, C8, and perfluoro reversed phases on diamond for solid-phase extraction.
AB  - In spite of advances in solid-phase extraction (SPE) technology there are certain
      disadvantages to current SPE silica-based, column packings. The pH range over
      which extraction can occur is limited and each column is generally only used
      once. New diamond-based reversed SPE phases (C(18), C(8), and perfluorinated)
      were developed in our laboratories. Studies were done which show that these
      phases do not have the same limitations as traditional silica-based stationary
      phases. The synthesis and properties of these diamond-based phases are presented,
      and the stability, percent recovery, and column capacity are given for the C(18)
      phase.

PMID- 19118838
TI  - Adsorption of poly(ethylene oxide) on smectite: Effect of layer charge.
AB  - The adsorption of polymers on clay is important in many applications. However the
      mechanisms of poly(ethylene oxide) (PEO) adsorption on smectite is not well
      elucidated at present. The aim of this study was to investigate the effect of
      layer charge density on the adsorption of PEO by smectite. The results indicated
      that both the hydrophobic interaction (between CH(2)CH(2) groups and siloxane
      surface) and the hydrogen bonding (between ether oxygen of PEO and structure OH
      of smectite) lead to PEO preferential adsorption on the surface of low-charge
      smectite. In addition, the delamination of low-charge smectite in water is
      enhanced upon PEO adsorption presumably due to the hydrophilic ether oxygen of
      adsorbed PEO.

PMID- 19118839
TI  - Sorption phenomena of modification of clinoptilolite tuffs by surfactant cations.
AB  - The sorption of cationic surfactant hexadecyltrimethylammonium (HDTMA) onto the
      solid/liquid interfaces of different clinoptilolite rich tuffs (CT) is examined.
      Examined were CT from Serbia with 75% clinoptilolite, CT from Turkey with 70%
      clinoptilolite, and CT from Croatia with 60% clinoptilolite. The sorption of
      HDTMA cations increased in the following order: CT from Serbia>CT from Turkey>CT
      from Croatia. The maximum amounts of sorbed HDTMA cations, normalized with regard
      to external cation exchange capacities of tuffs, were 1.79, 1.70, and 1.14 for
      Serbian, Turkish, and Croatian CT. FTIR analysis of samples with the maximum
      amount of sorbed HDTMA cations showed that HDTMA chains on Serbian CT adopt
      mainly a stretched all-trans conformation, while at the surfaces of CT from
      Turkey and Croatia the amount of gauche conformations increased. The zeta
      potentials of CT samples with the maximum amount of sorbed HDTMA cations and the
      sorption of benzoate anions on these samples increased in the following order: CT
      from Turkey>CT from Serbia>CT from Croatia. It can be assumed that on the surface
      of CT from Turkey iron (hydr)oxide clusters or nanoparticles with positive
      surface sites are present, due to which the isoelectric point is sifted toward
      lower and the zeta potential toward higher values. Therefore, the sorption of
      benzoate anions on modified CT from Turkey is also higher.

PMID- 19118840
TI  - Biscationic bicephalic (double-headed) amphiphiles with an aromatic spacer and a
      single hydrophobic tail.
AB  - We report the synthesis and aggregation studies of a homologous family of
      biscationic "bicephalic" amphiphiles. Each of has a linear alkoxy chain and two
      trimethylammonium bromide headgroups connected to a benzene ring. Krafft
      temperatures (T(K)) in water were determined by differential scanning calorimetry
      (DSC) and conductivity. Critical micelle concentration (cmc) and ionization
      degree (alpha) values were determined by monitoring the conductivity of aqueous
      solutions as a function of concentration, and confirmed by monitoring the (1)H
      NMR chemical shift of the terminal methyl group as a function of concentration.
      Values for log(cmc) decrease linearly with increasing chain length, with a
      smaller dependence on chain length than for single-headed amphiphiles, consistent
      with literature reports on other bicephalic amphiphiles. Comparison to two
      related amphiphiles, each with a single headgroup reveals that the addition of a
      second head group results in an increase in cmc and a decrease of T(K). These
      effects are attributed to greater water solubility due to the incorporation of a
      second, hydrophilic headgroup. The effect on alpha is also discussed.

PMID- 19118841
TI  - Tissue calcium content in piglets with inguinal or scrotal hernias or
      cryptorchidism.
AB  - Scrotal and inguinal hernias are of great economic importance to the pig
      industry. These lesions are thought to result from incomplete closure of the
      inguinal ring and/or a patent processus vaginalis. Impairment of programmed cell
      death (PCD) may be involved in these abnormalities. As tissue Ca(2+) overload may
      be used as a measure of cell death, the aim of this study was to determine the
      tissue Ca(2+) content in samples of hernia sac, peritoneum, cremaster muscle and
      aqueous fluid from newborn piglets with scrotal or inguinal hernias (n=18) or
      cryptorchidism (n=18). Control samples from healthy piglets (n=20) were also
      evaluated. Tissue Ca(2+) content was determined by atomic absorption
      spectrophotometry. Significantly less Ca(2+) was found in the sacs (0.005 mg/g
      wt), peritoneal tissue (0.100 mg/g wt) and cremaster muscles (0.008 mg/g wt) of
      piglets with inguinal or scrotal hernias compared with control tissues (0.184,
      0.144 and 0.048 mg/g wt for sacs, peritoneal tissue and cremaster muscles,
      respectively). These findings suggest that there may be perturbation of the
      apoptotic pathway in the urogenital tissues of affected piglets.

PMID- 19118842
TI  - Systemic administration of interleukin-10 attenuates early ischemic response
      following spinal cord ischemia reperfusion injury in rats.
AB  - BACKGROUND: The aim of this experimental study was to investigate the early
      effects of interleukin-10 (IL-10) and interleukin-1beta antagonist (anti-IL
      1beta) against cellular damage, inflammatory reactivity, lipid peroxidation
      (LPO), and myeloperoxidase (MPO) activity induced by spinal cord ischemia
      reperfusion injury (IRI). METHODS: Thirty-two single strain female Albino rats
      were divided into four groups: control (sham-operated), IRI-alone, IL-10-treated
      (100 mug/kg), and anti-IL-1beta-treated (1 mg/kg) groups after IRI. IRI was
      induced by balloon occlusion of the aorta and simultaneous hypovolemia during
      occlusion. The animals were sacrificed at 24 h. Histopathological and
      ultrastructural analyses, biochemical studies for determination of LPO and MPO
      activity and Comet assays (single cell electrophoresis for detecting DNA single
      strand breaks) were performed in all study groups. RESULTS: Compared with the
      levels of control (sham-operated) animals, IRI produced a significant increase in
      the levels of LPO and MPO activity, and prominent tissue damage characterized by
      leukocyte infiltration, edema and neuronal and glial damage in the affected
      spinal cord in 24 h. The administration of IL-10 decreased LPO and MPO activity,
      and suppressed initial inflammatory response in the first 24 h. The effects of
      anti-IL-1beta were limited to decrease in LPO activity without considerable
      evidence of cellular preservation. CONCLUSIONS: These data suggest that systemic
      administration of IL-10 attenuates the early ischemic response, and may restrict
      the tissue damage in the first 24 h after spinal cord ischemia reperfusion
      injury. Anti-IL-1beta has no considerable effect in this time window. The results
      of this preliminary study promote further studies with longer time windows on the
      effects of anti-inflammatory cytokines in spinal cord IRI.

PMID- 19118843
TI  - Monochloramine impairs caspase-3 through thiol oxidation and Zn2+ release.
AB  - BACKGROUND: Caspase-3, a pro-apoptotic enzyme, represents a class of proteins in
      which the active site contains reduced thiol (S-H) groups and is modulated by
      heavy metal cations, such as Zn(2+). We explored the effects of the thiol oxidant
      monochloramine (NH(2)Cl) on caspase-3 activity within cells of isolated rabbit
      gastric glands. In addition, we tested the hypothesis that NH(2)Cl-induced
      alterations of caspase-3 activity are modulated by oxidant-induced accumulation
      of Zn(2+) within the cytoplasm. MATERIALS AND METHODS: Isolated gastric glands
      were prepared from rabbit mucosa by collagenase digestion. Caspase-3 activity was
      measured colorimetrically in suspensions of healthy rabbit gastric glands,
      following exposure to various concentrations of NH(2)Cl with or without the zinc
      chelator TPEN [tetrakis-(2-pyridylmethyl)ethylene diamine] for 1 h, and re
      equilibration in Ringer's solution for 5 h. Conversion of procaspase-3 to active
      caspase-3 was monitored by Western blot. RESULTS: Monochloramine inhibited
      caspase-3 activity in a dose-dependent fashion. At concentrations of NH(2)Cl up
      to 100 microM, these effects were prevented if TPEN was given concurrently and
      were partly reversed if TPEN was given 1 h later. Caspase-3 activity was
      preserved by concurrent treatment with a thiol-reducing agent, dithiothreitol.
      CONCLUSIONS: At pathologically relevant concentrations, NH(2)Cl impairs caspase-3
      activity through oxidation of its thiol groups. Independently from its thiol
      oxidant effects on the enzyme, NH(2)Cl-induced accumulation of Zn(2+) in the
      cytoplasm is sufficient to restrain endogenous caspase-3 activity. Our studies
      suggest that some bacterially generated oxidants, such as NH(2)Cl, impair host
      pathways of apoptosis through release of Zn(2+) from endogenous pools.

PMID- 19118844
TI  - A prospective study on the influence of a fast-track program on postoperative
      fatigue and functional recovery after major colonic surgery.
AB  - INTRODUCTION: Enhanced Recovery After Surgery (ERAS) programs have demonstrated
      significant reduction in hospital stay for patients undergoing colonic surgery;
      however, their impact on long-term outcomes, such as postoperative fatigue (POF),
      has not been fully established. AIM: To assess the impact of an ERAS program on
      POF and recovery following elective open colonic surgery. METHOD: In a
      prospective study, 26 consecutive patients undergoing open colonic surgery under
      a conventional care plan were compared with 26 consecutive patients in an ERAS
      program. RESULTS: Demographic and clinical characteristics were comparable at
      baseline. The median duration of total hospital stay (4 versus 7 d, P < 0.001),
      rates of urinary tract infections (P = 0.028) and ileus (P = 0.042) were
      significantly smaller in the ERAS group. Postoperatively, POF significantly
      increased in both groups. However, peak POF score was significantly lower in the
      ERAS group (P = 0.001). In the first 30 d after surgery, Fatigue Consequence
      scores were also significantly smaller in the ERAS group. Overall, the total
      fatigue experience (P = 0.035) and the total fatigue impact (P = 0.005) were
      significantly smaller in the ERAS group. CONCLUSION: The impact of ERAS programs
      may extend beyond the commonly reported short-term outcomes, and ERAS may
      accelerate overall recovery and return to normal function.

PMID- 19118845
TI  - Triphala incorporated collagen sponge--a smart biomaterial for infected dermal
      wound healing.
AB  - BACKGROUND: Wound infection is a major problem in the medical community since
      many types of wounds are more prone to microbial contamination leading to
      infection. Triphala (a traditional ayurvedic herbal formulation) incorporated
      collagen sponge was investigated for its healing potential on infected dermal
      wound in albino rats. MATERIALS AND METHODS: Methanol extract of triphala was
      prepared and analyzed for the presence of catechin by high-pressure liquid
      chromatography analysis. Collagen sponge was prepared by incorporating triphala
      into collagen sponge. The triphala incorporated collagen was characterized by
      Fourier transform infrared spectroscopy, differential scanning calorimetry, and
      water uptake analysis. Infected wound was dressed with triphala incorporated
      collagen sponge. Wound reduction rate, collagen content, and matrix
      metalloproteinases in the granulation tissue, histology, and Fourier transform
      electron microscopy analysis were done to obtain the healing pattern. RESULTS:
      High-pressure liquid chromatography analysis showed the presence of (
      )epigallocatechin gallate. FT-IR spectroscopy study revealed the interaction of
      polyphenols with the collagen. Triphala incorporated collagen sponge has shown to
      increase thermal stability and water uptake capability, faster wound closure,
      improved tissue regeneration, collagen content at the wound site, and supporting
      histopathological parameters pertaining to wound healing. Matrix
      metalloproteinases expression was correlated well with reduction in the
      inflammatory phase, thus confirming efficacy of the dressing. CONCLUSIONS: Better
      healing efficacy of triphala incorporated collagen sponge may provides a
      scientific rationale for the use of this dressing as an effective wound cover in
      the management of infected dermal wound.

PMID- 19118847
TI  - The protective effect of ischemic preconditioning associated with altered gene
      expression profiles in intestinal grafts after reperfusion.
AB  - BACKGROUND: Ischemia-reperfusion injury after small bowel transplantation (SBT)
      has been considered as a trigger for early graft rejection. Ischemic
      preconditioning (IPC) may improve the tolerance of the small intestine to
      ischemic insults; however, the mechanism of IPC is still not completely
      elucidated. Accordingly, the aim of the present research is to investigate the
      molecular mechanism of IPC through a large-scale expression measurement of
      intragraft gene profiles by complementary DNA microarrays in SBT. MATERIALS AND
      METHODS: Three groups of rats were studied: S group (sham group), SBT group, and
      ISBT group (IPC plus SBT), in which IPC was carried out before the graft was
      harvested. Samples were collected from the different groups 1 h after
      reperfusion. Gene expression profiles of intestinal graft from the SBT group or
      ISBT group relative to gene expression profiles of normal intestine from the S
      group were analyzed respectively using 4096 gene chips. RESULTS: Microarray
      analysis showed that 14 genes were up-regulated more than 2-fold after
      reperfusion compared with normal intestine, and 17 genes were down-regulated in
      the SBT group. In the ISBT group, 84 genes with differential expression were
      detected after reperfusion compared with normal intestine. It was found that 16
      genes had differential expression in both the SBT and ISBT groups. These
      differentially expressed genes were primarily associated with cellular adhesion,
      energetic and substrate metabolism, and intracellular signal transduction. In
      addition, a number of novel genes were found. CONCLUSIONS: The protective effect
      of IPC was correlated with regulation of cellular adhesion, improvement on
      energetic and substrate metabolism, and activation of intracellular signal
      transduction.

PMID- 19118846
TI  - Exacerbation of bleomycin-induced injury and fibrosis by pneumonectomy in the
      residual lung of mice.
AB  - BACKGROUND: Lung resection after induction chemotherapy and/or radiotherapy for
      down-staging of locally advanced lung cancer can be complicated with lethal
      interstitial pneumonia. We studied the effects of pneumonectomy on bleomycin
      induced lung injury and fibrosis in mice. METHODS: The mice underwent left
      pneumonectomy or a sham thoracotomy after intratracheal administration of saline
      or bleomycin. Lung permeability index, wet-to-dry weight ratio, histological
      changes, collagen contents, and concentrations of inflammatory mediators and cell
      counts in broncho-alveolar lavage (BAL) fluid were assessed in the residual right
      lung 7 d after surgery. RESULTS: The index of capillary permeability, lung water
      content, and inflammatory cell counts in BAL fluid were significantly increased
      by pneumonectomy. These measurements were highest in the mice with both
      pneumonectomy and intratracheal administration of bleomycin. Similarly, fibrotic
      change in lung pathology, as well as an increase in lung collagen content, was
      most prominent in the mice exposed to both interventions. The BAL fluid
      concentrations of interleukin-1beta, interleukin-6, RANTES, and high mobility
      group box 1 were significantly increased by pneumonectomy and enhanced by the
      additional administration of bleomycin. CONCLUSIONS: The results of this study
      indicate that pneumonectomy alone causes noncritical lung injury, which amplifies
      the inflammatory response to bleomycin and promotes lung fibrosis. Several
      inflammatory mediators appear to be involved in the exacerbation of bleomycin
      induced lung injury and fibrosis.

PMID- 19118848
TI  - Plan-view photos, benthic grabs, and sediment-profile images: Using complementary
      techniques to assess response to seafloor disturbance.
AB  - A monitoring survey was conducted in July 2005 at the Rhode Island Sound Disposal
      Site (RISDS) as part of the Disposal Area Monitoring System (DAMOS) program. The
      survey included the collection of sediment-profile and plan-view images, and
      benthic biology grabs. Each of these techniques provides a different, yet
      complementary perspective on benthic community conditions. These complementary
      techniques aided in the assessment of the benthic recovery process within RISDS
      following the placement of dredged material from the Providence River and Harbor
      Maintenance Dredging Project (PRHMDP). Based on observed patterns of physical,
      chemical, and biological responses of seafloor environments to dredged material
      disposal activity it was expected that the benthic community within RISDS would
      be in an intermediate phase of recolonization (Stage II). Results of the 2005
      RISDS survey indicated that in the six months since disposal activities at RISDS
      had concluded, the biological community at RISDS was recovering relatively
      rapidly and Stages II and III infauna were present throughout the region.

PMID- 19118849
TI  - The effects of p-hydroxycinnamaldehyde from Alpinia galanga extracts on human
      chondrocytes.
AB  - Osteoarthritis (OA) is the most common form of arthritis and affects millions of
      people worldwide. Patients have traditionally been treated with non-steroidal
      anti-inflammatory drugs (NSAIDs), but these are associated with significant side
      effects. Purification of the acetone extract of Alpinia galanga afforded p
      hydroxycinnamaldehyde, as identified by nuclear magnetic resonance and mass
      spectrometry analyses. By exploiting the cartilage explant culture, p
      hydroxycinnamaldehyde suppressed loss of uronic acid, resulting in release of
      hyaluronan (HA), sulfated glycosaminoglycans (s-GAGs) and matrix
      metalloproteinases (MMPs). p-Hydroxycinnamaldehyde and interleukin-1beta (IL
      1beta), when incubated in primary human chondrocytes, also reduced release of HA,
      s-GAG and MMP-2. The results demonstrated: (a) that expression levels of the
      catabolic genes MMP-3 and MMP-13 were suppressed and (b) mRNA expression levels
      of anabolic genes of collagen II, SOX9 and aggrecan were increased. This study
      shows that p-hydroxycinnaldehyde from A. galanga Linn. is a potential therapeutic
      agent for treatment of OA.

PMID- 19118850
TI  - Detection and genetic characterisation of Hepatitis E virus in Czech pig
      production herds.
AB  - The objective of the present study was to carry out a small surveillance
      programme in Czech pig production herds using the nested reverse transcriptase
      polymerase chain reaction (nRT-PCR) technique to trace Hepatitis E virus (HEV) in
      different biological samples and to characterise the detected swine HEV isolates
      by phylogenetic analysis. A total of 32 piglets from 11 herds clinically
      suspected of postweaning multisystemic wasting syndrome (PMWS) were examined.
      Bile, liver tissue and serum samples were collected from each animal. Due to the
      high genetic variability of HEV, three sets of primers targeting each of the open
      reading frames (ORFs) of its genome were used. HEV RNA was most frequently
      detected in the bile samples (40.0%), followed by liver tissue (16.1%) and serum
      (3.2%). Seven (63.6%) of the 11 monitored farms were found to have at least one
      HEV RNA positive piglet. Specific 242 bp sequences within the ORF1 coding non
      structural proteins were sequenced and phylogenetically analysed. Phylogenetic
      analysis using the neighbor-joining and maximum parsimony method confirmed that
      all detected Czech swine HEV isolates belonged to genotype III. Comparison of the
      Czech swine HEV isolates with corresponding sequences of swHEV available in
      GenBank failed to find any 100% homologous HEV isolate.

PMID- 19118851
TI  - [Multifocal motor neuropathy: a retrospective study of sensory nerve conduction
      velocities in long-term follow-up of 21 patients].
AB  - INTRODUCTION: Multifocal motor neuropathy is a well described condition
      characterized by slowly progressive, predominantly distal, asymmetric limb
      weakness and wasting, predominantly in the arms within an anatomical distribution
      of individual motor nerves, with minimal or no sensory involvement. METHOD: The
      aim of this retrospective study was to look for a significant reduction of the
      amplitude of sensory potentials in a cohort of 21 patients with defined
      multifocal motor neuropathy according to the Workshop Report criteria [Workshop
      Report, 2001. 79th ENMC International Workshop. Multifocal motor neuropathy 14-15
      April 2000, Hilversum. The Netherlands. Muscle Nerve 11, 309-314], within a
      follow-up of at least 3 years. RESULT: Thirteen patients (62%) (Group 1) had a
      reduction of the amplitude of at least one sensory potential, of whom four
      patients had abnormalities of two or more sensory potentials, while eight
      patients (Group 2) had no abnormality. No significant differences were found for
      gender, age at onset, number of involved motor nerves, CSF protein count,
      presence/absence of anti-GM1 serum antibodies and response to IgIV between the
      two groups. CONCLUSION: This study underlines the difficulty in defining criteria
      for multifocal motor neuropathies capable of distinguishing them from other
      chronic acquired demyelinating polyneuropathies, and mainly from multifocal
      acquired demyelinating sensory and motor (MADSAM) neuropathy, also called Lewis
      Sumner's syndrome.

PMID- 19118852
TI  - Analysis of an acute Chagas disease outbreak in the Brazilian Amazon: human
      cases, triatomines, reservoir mammals and parasites.
AB  - An outbreak of Chagas disease occurred in Mazagao, Amapa, Brazilian Amazon in
      1996. Seventeen of 26 inhabitants presented symptoms compatible with acute Chagas
      disease and were submitted to parasitological and serological tests. All 17 were
      positive in at least one parasitological test and 11 were also IgM or IgG anti
      Trypanosoma cruzi positive. The nine asymptomatic patients were negative for
      parasites and one was positive for IgG anti-T. cruzi. Sixty-eight triatomines
      were captured (66 Rhodnius pictipes; two Panstrongylus geniculatus); 45 were
      infected with T. cruzi (43 R. pictipes; two P. geniculatus). Thirteen
      trypanosomatid strains were isolated: eight from humans and five from R.
      pictipes. Four were genotyped as T. cruzi I (two from humans; two from R.
      pictipes), seven as T. cruzi Z3 (six from humans; one from R. pictipes) and two
      as T. cruzi Z3 and T. rangeli (from R. pictipes). Treatment started for all
      patients leading to a decrease in parasitaemia in 16 during the follow-up period
      (6 months, 1, 5 and 7 years). All were serologically negative 7 years post
      treatment. There was an overlap of genotypes in the same ecotope, raising the
      possibility of transmission through the oral route and the need for early
      therapeutic intervention for better patient management in the Brazilian Amazon.

PMID- 19118853
TI  - Platelet function and the von Willebrand factor antigen in the hepatosplenic form
      of schistosomiasis mansoni.
AB  - Forty-five individuals with hepatosplenic schistosomiasis mansoni were studied
      with the aim of measuring levels of von Willebrand factor antigen (vWF:Ag),
      detecting abnormalities in platelet morphology and aggregation, and identifying
      changes to surface antigens. Haemograms, platelet aggregation tests, flow
      cytometry investigations of CD41/CD42b antibody and vWF:Ag assays were performed.
      Mean platelet counts were low (77,522/mm3) and 82.2% of patients presented
      thrombocytopenia. An inverse relationship between spleen size and platelet count
      was seen. Macroplatelets were found in 57.1% of patients, indicating good bone
      marrow response, but were insufficient to compensate for the decrease in
      platelets due to splenomegaly. Decreased or absent platelet aggregation was seen
      in 50% of patients, probably due to low platelet counts. Markers for GPIIb/IIIa
      were normal in more than 90% of patients, not supporting the increased capture
      and destruction of platelets in the spleen that is hypothesized to occur with
      cirrhosis. Similar to cirrhosis, vWF:Ag levels were high or very high in 70.5% of
      patients. High levels of vWF:Ag were associated with platelet counts
      <100,000/mm3, larger spleen diameter and oesophageal varices. In conclusion,
      hepatosplenic schistosomiasis leads to a lower platelet count due to pooling in
      the spleen and, consequently, impaired aggregation, but not to increased capture
      and destruction of platelets in the spleen. High vWF:Ag levels probably promote
      stabilization of platelet microaggregates and prevent minor manifestations of
      thrombocytopenia such as petechiae, ecchymosis and gingival bleeding.

PMID- 19118854
TI  - Risks associated with vaccinia virus in the laboratory.
AB  - Vaccinia virus (VACV) is used commonly in research laboratories. Non-highly
      attenuated strains of VACV are potentially pathogenic in humans, and VACV
      vaccination and biosafety level 2 facilities and protocols are currently
      recommended for vaccinated laboratory workers in the United States who handle non
      highly attenuated strains of the virus. Despite this, laboratory-related VACV
      exposures continue to occur and a number of recent instances of VACV infection in
      non-vaccinated laboratory workers have been documented. We provide a discussion
      of the usage and risks associated with VACV in laboratory research.

PMID- 19118855
TI  - N-nitrosodimethylamine (NDMA) as a product of potassium permanganate reaction
      with aqueous solutions of dimethylamine (DMA).
AB  - The reactivity of permanganate with dimethylamine, as possible path of NDMA
      formation, has been investigated. The results have shown that potassium
      permanganate reaction with aqueous solutions of dimethylamine (DMA) leads to the
      formation of N-nitrosodimethylamine (NDMA). The contact time, the molar ratio of
      permanganate and DMA, pH and presence of nitrite are the key factors influencing
      the efficiency of NDMA formation. Significant conversion rates of DMA to NDMA
      were observed only for the high doses of permanganate, which were many times
      higher than those typically used in water treatment. This reaction however is of
      importance for water treatment technology, since it shows the possibility of NDMA
      formation as a result of oxidation of DMA. It is likely that nitrosation is the
      main path of the reaction. An important role of MnO2 suspension, formed as a
      result of permanganate reduction in NDMA formation is emphasized. Significant
      influence of MnO2 suspension on NDMA formation should draw our attention to the
      potential impact of MnO2 activated filtration beds on NDMA formation.

PMID- 19118856
TI  - Evaluation of public health risks at recreational beaches in Lake Michigan via
      detection of enteric viruses and a human-specific bacteriological marker.
AB  - Each year the National Resource Defense Council addresses the quality of US
      beaches by routine bacterial indicators. In the Great Lakes region the indicator
      used is Escherichia coli and for 2007 more beaches were closed and impacted than
      ever before. In this study, water quality was addressed at two Lake Michigan
      Beaches over the 2004 swimming season by monitoring infectious enteric viruses by
      cell culture and integrated PCR and for a human sewage marker based on the
      Enterococcal Surface Protein (esp). Our goals for this study were to 1) examine
      the occurrence and variety of human enteric viruses present during peak usage of
      the beaches 2) determine key variables for development of predictive models for
      viruses; and 3) use quantitative risk assessment to estimate the potential health
      impact. Our results demonstrate that for both beaches predictive models of virus
      pollution were best described utilizing physical parameters like wind speed, wind
      direction and water temperature. The esp marker was not predictive of human
      viruses. The daily risk of acquiring a viral infection at either of the beaches
      ranged from 0.2 to 2.4/1000 swimmers using a quantitative microbial risk
      assessment model, with three swims during a day at the beach for children and
      over the season, the risk was 9-15/1000 swimmers using adenovirus as the model.
      CONCLUSIONS: Lake Michigan recreational beaches are being adversely impacted by
      human fecal pollution. Monitoring for the traditional indicators of water quality
      does not address viral risks and models can be developed and potentially used as
      real-time water quality forecasting tools.

PMID- 19118857
TI  - Efficacy of controlled-release KMnO4 (CRP) for controlling dissolved TCE plume in
      groundwater: a large flow-tank study.
AB  - A well-based, reactive barrier system using controlled-release potassium
      permanganate (CRP system) was recently developed as a long-term treatment option
      for dilute plumes of chlorinated solvents in groundwater. In this study, we
      performed large-scale (L x W x D = 8 m x 4 m x 2 m) flow-tank experiments to
      examine remedial efficacy of the CRP system. A total of 110 CRP rods (OD x L=5 cm
      x 150 cm) were used to construct a well-based CRP system (L x W x D = 3 m x 4 m x
      1.5 m) comprising three discrete barriers installed at 1-m interval downstream.
      Natural sands having oxidant demand of 3.7 g MnO(4)(-)kg(-1) for 500 mg L(
      1)MnO(4)(-) were used as porous media. After MnO(4)(-) concentrations were
      somewhat stabilized (0.5-6.0 mg L(-1)), trichloroethylene (TCE) plume was flowed
      through the flow-tank for 53 d by supplying 1.19 m(3)d(-1) of TCE solution. Mean
      initial TCE concentrations were 87 microg L(-1) for first 20 d and 172 microg L(
      1) for the next 33 d. During TCE treatment, flow velocity (0.60md(-1)), pH (7.0
      8.2), and concentrations of dissolved metals ([Al]=0.7 mg L(-1), [Fe]=0.01 mg L(
      1)) showed little variations. The MnO(2)(s) contents in the sandy media measured
      after the TCE treatment ranged from 21 to 26 mg kg(-1), slightly increased from
      mean baseline value of 17 mg kg(-1). Strengths of the TCE plume considerably
      diminished by the CRP system. For the 87 microg L(-1) plume, TCE concentrations
      decreased by 38% (53), 67% (29), and 74% (23 microg L(-1)) after 1st, 2nd, and
      3rd barriers, respectively. For the 172 microg L(-1) plume, TCE concentrations
      decreased by 27% (125), 46% (93), and 65% (61 microg L(-1)) after 1st, 2nd, and
      3rd barriers, respectively. Incomplete destruction of TCE plume was attributed to
      the lack of lateral dispersion in the unpumped well-based barrier system.
      Development of delivery systems that can facilitate lateral spreading and mixing
      of permanganate with contaminant plume is warranted.

PMID- 19118858
TI  - Oxidative degradation of 1,5-naphthalenedisulfonic acid in aqueous solutions by
      microwave irradiation in the presence of H2O2.
AB  - Sulfonated aromatic pollutants such as Armstrong's acid, or 1,5
      naphthalenedisulfonic acid (NDS), are recalcitrant to environmental breakdown and
      microbial treatment. This study investigated the effects of H(2)O(2)
      concentration, pH, microwave (MW) power and irradiation time on the oxidative
      degradation of NDS in aqueous solutions. The formation of hydroxyl radicals as
      the active oxidant was confirmed by electron paramagnetic resonance spin
      trapping. A combination of both H(2)O(2) and MW heating proved essential for NDS
      degradation. Degradation factors of f70% were obtained after about 20min of
      irradiation at [H(2)O(2)]:[NDS] ratios=10. Acidic conditions were found to be
      more favorable to the degradation of NDS, and the process follows pseudo-first
      order kinetics. Attempts to scale-up the process using a conventional MW reactor
      provided less striking results.

PMID- 19118859
TI  - Electrochemical incineration of cresols: a comparative study between PbO2 and
      boron-doped diamond anodes.
AB  - The electrooxidation of aqueous solutions containing 5mM of o-, m- and p-cresol
      at pH 4.0 has been investigated using a flow filter-press reactor with a boron
      doped diamond (BDD) under galvanostatic electrolysis. All cresols are degraded at
      similar rate up to attaining overall mineralization. Comparable treatment of the
      m-cresol effluent on PbO(2) leads to partial electrochemical incineration.
      However, this pollutant is more rapidly removed with PbO(2) than with BDD. The
      decay kinetics of all cresols follows a pseudo-first-order reaction. Aromatic
      intermediates such as 2-methylhydroquinone and 2-methyl-p-benzoquinone and
      carboxylic acids such as maleic, fumaric, pyruvic, malonic, tartronic, glycolic,
      glyoxylic, acetic, oxalic and formic, have been identified and followed during
      the m-cresol treatment by chromatographic techniques. From these oxidation by
      products, a plausible reaction sequence for m-cresol mineralization on both
      anodes is proposed. The energy consumption for the corresponding electrochemical
      process is also calculated.

PMID- 19118861
TI  - Effects of turning frequency on compost stability and some chemical
      characteristics in a rotary drum composter.
AB  - Effect of turning frequency on quality, namely some chemical characteristics
      (temperature, moisture content, pH, electrical conductivity, total organic
      matter, nitrogen dynamics, phosphorus and trace elements) and stability of
      compost (biochemical oxygen demand, chemical oxygen demand, rate of oxygen
      consumption and carbon dioxide evolution) in a rotary drum were studied.
      Composting was stimulated by three turns of rotary drum at different time
      intervals i.e. at the gap of 6h (Run A), 12h (Run B), 18 h (Run C) and 24h (Run
      D) for 15 d. It was observed that Run D (24h turning frequency) caused longer
      thermophilic phase (4d) with a higher rise at temperature 58 degrees C;
      consequently, peak of maximum temperature was shifted along with the increase of
      turning frequency. Around 23% of available carbon in Run D was utilized by micro
      organisms and contained lower final electrical conductivity (1.32 dS m(-1))
      possibly causing lesser phytotoxicity effects on the growth of plants. The
      percentage increase in total nitrogen and total phosphorus (organic and
      inorganic) in Run D was found to be 45% and 37% as compared to 7% and 17%, 6% and
      32% and 18% and 30% in Run A, B, and C, respectively, indicating higher
      mineralization. The final values of respiration rates (CO(2) evolution and oxygen
      uptake rate) for Run D was found to be the lowest, nevertheless, other runs also
      provided relatively stable compost.

PMID- 19118860
TI  - Polychlorinated dibenzo-p-dioxin and dibenzofurans (PCDD/Fs), polybrominated
      diphenyl ethers (PBDEs), and polychlorinated biphenyls (PCBs) monitored by tree
      bark in an E-waste recycling area.
AB  - To investigate the environmental levels and profiles of polychlorinated dibenzo-p
      dioxins and dibenzofurans (PCDD/Fs), polybrominated diphenyl ethers (PBDEs), and
      polychlorinated biphenyls (PCBs), tree bark samples (n=22) were collected from
      Luqiao, an E-waste recycling area, in east China in July 11-13, 2006. The average
      concentrations of PCDD/Fs, PBDEs, and PCBs determined by isotope dilution-high
      resolution gas chromatography (HRGC) coupled with high resolution mass
      spectrometer (HRMS) were 0.1+/-0.0, 1.4+/-0.2, and 6.5+/-0.8 microg g(-1) lipid
      weight, respectively. PCDD/F-toxic equivalent (TEQ, WHO-1998), PCB-TEQs, and
      total dioxin-like TEQs were 1.3+/-0.1, 0.5+/-0.0, and 1.8+/-0.2 ng g(-1) lipid
      weight, respectively. The profiles of these pollutants in the tree bark were also
      discussed. Tetra-CDFs, deca-BDE and tri-CBs were the main homologues and
      accounted for 47% of total PCDD/Fs, 79.3% of total PBDEs, and 33.2% of total
      PCBs, respectively; As for TEQs, 2,3,4,7,8-PeCDF and PCB126 were the main
      contributors and accounted for 36% of the total PCDD/F-TEQs and 81.2% of the
      total PCB-TEQs, respectively. High accumulation of PCDD/Fs, PBDEs, and PCBs
      detected in the tree bark indicated heavy contaminations of these pollutants in
      Luqiao area.

PMID- 19118862
TI  - Removal of ammonia by immobilized Nitrosomonas europaea in a biotrickling filter
      packed with polyurethane foam.
AB  - A biotrickling filter with Nitrosomonas europaea immobilized on polyurethane foam
      is proposed for treating ammonia contaminated air. The effect of the surface
      velocity of the recirculation medium, nitrite concentration, pH, empty bed
      residence time (EBRT) and ammonia inlet load on the NH(3) removal process was
      investigated. The total amount of biomass immobilized on the carrier was 3.29+/
      0.52 x 10(10) cells g(-1) dry carrier. The maximum elimination capacity of the
      biotrickling filter was 270 g Nm(-3)h(-1) at pH 7.5, an EBRT of 11s, and nitrite
      concentrations below 100mM. These results show that system studied can be
      considered as a viable alternative for the treatment of gaseous emissions
      containing high concentrations of ammonia.

PMID- 19118863
TI  - Auto- and heterotrophic acidophilic bacteria enhance the bioremediation
      efficiency of sediments contaminated by heavy metals.
AB  - This study deals with bioremediation treatments of dredged sediments contaminated
      by heavy metals based on the bioaugmentation of different bacterial strains. The
      efficiency of the following bacterial consortia was compared: (i) acidophilic
      chemoautotrophic, Fe/S-oxidising bacteria, (ii) acidophilic heterotrophic
      bacteria able to reduce Fe/Mn fraction, co-respiring oxygen and ferric iron and
      (iii) the chemoautotrophic and heterotrophic bacteria reported above, pooled
      together, as it was hypothesised that the two strains could cooperate through a
      mutual substrate supply. The effect of the bioremediation treatment based on the
      bioaugmentation of Fe/S-oxidising strains alone was similar to the one based only
      on Fe-reducing bacteria, and resulted in heavy-metal extraction yields typically
      ranging from 40% to 50%. The efficiency of the process based only upon
      autotrophic bacteria was limited by sulphur availability. However, when the
      treatment was based on the addition of Fe-reducing bacteria and the Fe/S
      oxidizing bacteria together, their growth rates and efficiency in mobilising
      heavy metals increased significantly, reaching extraction yields >90% for Cu, Cd,
      Hg and Zn. The additional advantage of the new bioaugmentation approach proposed
      here is that it is independent from the availability of sulphur. These results
      open new perspectives for the bioremediation technology for the removal of heavy
      metals from highly contaminated sediments.

PMID- 19118864
TI  - Organic residues as immobilizing agents in aided phytostabilization: (I) effects
      on soil chemical characteristics.
AB  - A greenhouse experiment was conducted to evaluate the effect of three different
      organic residues, sewage sludge (SS), municipal solid waste compost (MSWC), and
      garden waste compost (GWC), as immobilizing agents in aided phytostabilization of
      a highly acidic metal-contaminated soil, affected by mining activities, using
      perennial ryegrass (Lolium perenne L.). The organic residues were applied at 25,
      50 and 100 Mg ha(-1) (dry weight basis), and their effects on soil chemical
      characteristics and on relative plant growth and metal concentrations were
      assessed. All the organic residues tested immobilized Cu, Pb and Zn, decreasing
      their mobile fractions. This was corroborated by negative correlations obtained
      between mobile Cu, Pb and Zn and other soil chemical characteristics, which rose
      as a consequence of the amendments applied (i.e., pH, electrical conductivity,
      organic matter, nitrogen content, available P and available K), and by the
      multivariate exploratory techniques performed that showed an inverse correlation
      between these groups of variables. The greatest increase in ryegrass relative
      growth (more than three times) was obtained in the presence of 50 MgMS WC ha(-1),
      followed by SS at the same application dosage. GWC did not contribute to an
      increase in shoot growth, due to its small capacity to correct soil acidity and
      to supply essential macronutrients (N, P, K). No extractant was able of
      demonstrating by a linear correlation the uptake of Cu, Pb and Zn by ryegrass.
      This plant was therefore not a good "indicator" of Cu, Pb and Zn availability in
      the soil. The results obtained in this study suggest that ryegrass can be used in
      aided phytostabilization for this type of mine contaminated soils and that MSWC,
      and to a minor extent SS, applied at 50Mg ha(-1), were effective in the in situ
      immobilization of metals, improving soil chemical properties and leading to a
      large increase in plant biomass.

PMID- 19118865
TI  - Particle size distributions and health-related exposures of polychlorinated
      dibenzo-p-dioxins and dibenzofurans (PCDD/Fs) of sinter plant workers.
AB  - This study measured particle size distributions of polychlorinated dibenzo-p
      dioxins and dibenzofurans (PCDD/Fs) in two workplace atmospheres of the sintering
      grate and rough roll shredder in a sintering plant, and to assess their workers'
      health-related exposures. We found that the PCDD/F concentration of the sintering
      grate (site A=14.47 pg m(-3)) was lower than that of the rough roll shredder
      (site B=17.20 pg m(-3)). Particle size distributions of PCDD/Fs were in the form
      of the unimodal with the mass median aerodynamic diameter (MMAD) of 4.74 microm
      and 5.23 microm, and geometric standard deviation (sigma(g)) of 3.15 and 2.15 for
      the site A and B, respectively. The above results suggest that the workplace of
      the site A had a less fraction of coarse particles than that of the site B. The
      estimated PCDD/F concentrations of the inhalable fraction (11.0 pg m(-3)) and
      thoracic fraction (8.89 pg m(-3)) of the site A were lower than those of the site
      B (12.4 and 9.39 pg m(-3), respectively). But to the contrary the estimated
      respirable fraction of the site A (5.05 pg m(-3)) was slightly higher than that
      of the site B (4.93 pg m(-3)). Our results clearly indicate the importance to
      conduct particle size segregating samplings for assessing human PCDD/F exposures.

PMID- 19118866
TI  - Allometric scaling of infraorbital surface topography in Homo.
AB  - Infraorbital morphology is often included in phylogenetic and functional analyses
      of Homo. The inclusion of distinct infraorbital configurations, such as the
      "canine fossa" in Homo sapiens or the "inflated" maxilla in Neandertals, is
      generally based on either descriptive or qualitative assessments of this
      morphology, or simple linear chord and subtense measurements. However, the
      complex curvilinear surface of the infraorbital region has proven difficult to
      quantify through these traditional methods. In this study, we assess infraorbital
      shape and its potential allometric scaling in fossil Homo (n=18) and recent
      humans (n=110) with a geometric morphometric method well-suited for quantifying
      complex surface topographies. Our results indicate that important aspects of
      infraorbital shape are correlated with overall infraorbital size across Homo.
      Specifically, individuals with larger infraorbital areas tend to exhibit
      relatively flatter infraorbital surface topographies, taller and narrower
      infraorbital areas, sloped inferior orbital rims, anteroinferiorly oriented
      maxillary body facies, posteroinferiorly oriented maxillary processes of the
      zygomatic, and non-everted lateral nasal margins. In contrast, individuals with
      smaller infraorbital regions generally exhibit relatively depressed surface
      topographies, shorter and wider infraorbital areas, projecting inferior orbital
      rims, posteroinferiorly oriented maxillary body facies, anteroinferiorly oriented
      maxillary processes, and everted lateral nasal margins. These contrasts form a
      continuum and only appear dichotomized at the ends of the infraorbital size
      spectrum. In light of these results, we question the utility of incorporating
      traditionally polarized infraorbital morphologies in phylogenetic and functional
      analyses without due consideration of continuous infraorbital and facial size
      variation in Homo. We conclude that the essentially flat infraorbital surface
      topography of Neandertals is not unique and can be explained, in part, as a
      function of possessing large infraorbital regions, the ancestral condition for
      Homo. Furthermore, it appears likely that the diminutive infraorbital region of
      anatomically modern Homo sapiens is a primary derived trait, with related
      features such as depressed infraorbital surface topography expressed as
      correlated secondary characters.

PMID- 19118867
TI  - New geochronological, paleoclimatological, and archaeological data from the
      Narmada Valley hominin locality, central India.
AB  - The oldest known fossil hominin in southern Asia was recovered from Hathnora in
      the Narmada Basin, central India in the early 1980's. Its age and taxonomic
      affinities, however, have remained uncertain. Current estimates place its maximum
      age at >236ka, but not likely older than the early middle Pleistocene. The
      calvaria, however, could be considerably younger. We report recent fieldwork at
      Hathnora and associated Quaternary type-sections that has provided new geological
      and archaeological insights. The portion of the exposed 'Boulder Conglomerate'
      within the Surajkund Formation, which forms a relict terrace and has yielded the
      hominin fossils, contains reworked and stylistically mixed lithic artifacts and
      temporally mixed fauna. Three mammalian teeth stratigraphically associated with
      the hominin calvaria were dated by standard electron spin resonance (ESR).
      Assuming an early uranium uptake (EU) model for the teeth, two samples collected
      from the reworked surface deposit averaged 49+/-1ka (83+/-2ka, assuming linear
      uptake [LU]; 196+/-7ka assuming recent uptake [RU]). Another sample recovered
      from freshly exposed, crossbedded gravels averaged 93+/-5ka (EU), 162+/-8ka (LU)
      or 407+/-21ka (RU). While linear uptake models usually provide the most accurate
      ages for this environment and time range, the EU ages represent the minimum
      possible age for fossils in the deposit. Regardless, the fossils are clearly
      reworked and temporally mixed. Therefore, the current data constrains the minimum
      possible age for the calvaria to 49+/-1ka, although it could have been reworked
      and deposited into the Hathnora deposit any time after 160ka (given the LU uptake
      ages) or earlier (given the RU ages). At Hathnora, carbonaceous clay, bivalve
      shells, and a bovid tooth recovered from layers belonging to the overlying Baneta
      Formation have yielded (14)C ages of 35.66+/-2.54cal ky BP, 24.28+/-0.39cal ky
      BP, and 13.15+/-0.34ky BP, respectively. Additional surveys yielded numerous
      lithics and fossils on the surface and within the stratigraphic sequence. At the
      foot of the Vindhyan Hills 2km from the river, we recovered a typologically Early
      Acheulean assemblage comprised of asymmetrical bifaces, large cleavers with
      minimal working, trihedral picks, and flake tools in fresh condition. These tools
      may be the oldest Acheulean in the Narmada Valley. Several lithics recovered from
      the Dhansi Formation may represent the first unequivocal evidence for an early
      Pleistocene hominin presence in India. In situ invertebrate and vertebrate
      fossils, pollen, and spores indicate a warm, humid climate during the late middle
      Pleistocene. High uranium concentrations in the mammalian teeth indicate exposure
      to saline water, suggesting highly evaporative conditions in the past. Late
      Pleistocene sediment dated between 24.28+/-0.39cal ky BP and 13.15+/-340ky BP has
      yielded pollen and spores indicating cool, dry climatic conditions corresponding
      to Oxygen Isotope Stage 2 (OIS 2). An early Holocene palynological assemblage
      from the type locality at Baneta shows evidence for relatively dry conditions and
      a deciduous forest within the region. The Dhansi Formation provisionally replaces
      the Pilikarar Formation as the oldest Quaternary formation within the central
      Narmada Basin. The Baneta Formation, previously dated at 70ka to 128ka,
      correlates with the late Pleistocene and early Holocene. Our results highlight
      the need for further Quaternary geological and paleoanthropological research
      within the Narmada Basin, especially because dam construction threatens these
      deposits.

PMID- 19118868
TI  - Modelling and simulation of concrete leaching under outdoor exposure conditions.
AB  - Recently, a demand regarding the assessment of release of dangerous substances
      from construction products was raised by European Commission which has issued the
      Mandate M/366 addressed to CEN. This action is in relation with the Essential
      Requirement No. 3 "Hygiene, Health and Environment" of the Construction Products
      Directive (89/106/EC). The potential hazard for environment and health may arise
      in different life cycle stages of a construction product. During the service life
      stage, the release of substances due to contact with the rain water is the main
      potential hazard source, as a consequence of the leaching phenomenon. The
      objective of this paper is to present the development of a coupled chemical
      transport model for the case of a concrete based construction product, i.e.
      concrete paving slabs, exposed to rain water under outdoor exposure conditions.
      The development of the model is based on an iterative process of comparing the
      experimental results with the simulated results up to an acceptable fit. The
      experiments were conducted at laboratory scale (equilibrium and dynamic leaching
      tests) and field scale. The product was exposed for one year in two types of
      leaching scenarios under outdoor conditions, "runoff" and "stagnation", and the
      element release was monitored. The model was calibrated using the experimental
      data obtained at laboratory scale and validated against measured field data, by
      taking into account the specific rain water balance and the atmospheric CO2
      uptake as input parameters. The numerical tool used in order to model and
      simulate the leaching behaviour was PHREEQC, coupled with the Lawrence Livermore
      National Laboratory (LLNL) thermodynamic data base. The simulation results are
      satisfying and the paper demonstrates the feasibility of the modelling approach
      for the leaching behaviour assessment of concrete type construction materials.

PMID- 19118869
TI  - Natural organic matter and sunlight accelerate the degradation of 17ss-estradiol
      in water.
AB  - Nanomolar concentrations of steroid hormones such as 17beta-estradiol can
      influence the reproductive development and sex ratios of invertebrate and
      vertebrate populations. Thus their release into surface and ground waters from
      wastewater facilities and agricultural applications of animal waste is of
      environmental concern. Many of these compounds are chromophoric and susceptible
      to photolytic degradation. High intensity UV-C radiation has been demonstrated to
      degrade some of these compounds in engineered systems. However, the degradation
      efficacy of natural solar radiation in shallow fresh waters is less understood.
      Here photolytic experiments with 17beta-estradiol demonstrated modest
      photodegradation (~26%) when exposed to simulated sunlight between 290 and 720
      nm. Photodegradation significantly increased (~40-50%) in the presence of 2.0
      15.0 mg/l of dissolved organic carbon (DOC) derived from humic acids of the
      Suwannee River, GA. However, rates of photodegradation reached a threshold at
      approximately 5.0 mg/l DOC. Observed suppression of photolysis in the presence of
      a radical inhibitor (i.e. 2-propanol) indicated that a significant proportion of
      the degradation was due to radicals formed from the photolysis of DOC. Although
      photodegradation was greatest in full sunlight containing UV-B (290-320 nm),
      degradation was also detected with UV-A (320-400 nm) and visible light (400-720
      nm) alone.

PMID- 19118870
TI  - HLA class II and autoimmunity: epitope selection vs differential expression.
AB  - Autoimmune diseases like rheumatoid arthritis (RA), multiple sclerosis, psoriasis
      and insulin-dependent diabetes mellitus are subject to a complex pathogenesis
      controlled by multiple genes and numerous environmental factors. The strongest
      genetic association is with certain HLA class II haplotypes and we here summarize
      the evidence supporting differential expression as a mechanism supporting the
      autoimmune process.

PMID- 19118871
TI  - Concurrence of klinefelter syndrome with hypospadias and chordee in identical
      twins: a rare presentation.
AB  - Klinefelter syndrome (KFS), is the most common disorder of the sex chromosomes,
      affecting 1/1000 male births, and presents with underdeveloped secondary sexual
      characteristics, infertility, and increased urinary excretion of gonadotropin.
      External genitourinary malformations in KFS are not common, except for small
      testes. We present identical twins with a 47XXY karyotype and discordant
      hypospadias and concomitant chordee. To our knowledge, this is the first report
      of such an association. The diverse possible etiologies explaining the
      relationship between the presenting congenital defects in identical twins are
      discussed. We believe that 1 known genetic malformation such as KFS warrants
      additional urologic assessment.

PMID- 19118872
TI  - Vena cava air embolism after traumatic Foley catheter placement.
AB  - We report a case of traumatic Foley catheter placement and manipulation that
      resulted in a large, symptomatic, vena cava air embolism confirmed on computed
      tomography. To the best of our knowledge, our report represents the first case of
      a large, symptomatic, vena cava air embolism as a direct result of Foley catheter
      trauma. The included computed tomography images are unique in that they
      simultaneously show an improperly positioned Foley catheter and a large vena cava
      air embolism.

PMID- 19118873
TI  - Are lower urinary tract symptoms influenced by metabolic syndrome?
AB  - OBJECTIVES: To determine the role of the metabolic syndrome (MS) in the genesis
      of lower urinary tract symptoms (LUTS) in both sexes. The MS and LUTS are highly
      prevalent disorders, both increasing with increasing age. METHODS: Participants
      in a health-screening project underwent a detailed health examination, including
      all factors associated with the MS, and were assessed regarding LUTS. The MS was
      defined according to the International Diabetes Federation consensus definition
      of 2005, and LUTS were quantified using the International Prostate Symptom Score
      (IPSS). RESULTS: A total of 2371 men (mean age 46.1 years) and 731 women (mean
      age 53.9 years) were analyzed. In the men, moderate-to-severe LUTS (IPSS >7) were
      present in 13.1%; in the women, the corresponding value was 23.5%. The proportion
      of the MS diagnosed during the health investigation was 33.8% in the men and
      30.2% in the women. On multiple linear regression analysis, the MS was not
      associated with the IPSS, IPSS obstructive or irritative subscore, or LUTS. The
      proportion of LUTS and mean IPSS did not significantly differ regarding the
      presence or absence of the MS in either sex. CONCLUSIONS: According to our
      results, the MS did not turn out to be significantly and independently involved
      in the genesis of LUTS in men or women.

PMID- 19118874
TI  - Laparoscopic marsupialization before inguinal repair of large abdominoscrotal
      hydroceles in infants: observation of natural history and description of
      technique.
AB  - OBJECTIVES: To develop a surgical procedure that would minimize the difficult
      proximal spermatic cord dissection during excision of the abdominal component of
      abdominoscrotal hydroceles (ASHs). Because the abdominal component is derived
      from the peritoneum, we postulated that complete removal of all tissue is
      unnecessary and laparoscopic creation of a wide peritoneal window is sufficient
      for treatment before inguinal repair of the scrotal component. METHODS: We
      describe a series of 4 patients who underwent laparoscopic marsupialization of
      the abdominal component of an ASH before inguinal repair. In addition, we
      describe the natural history of a patient who had had initial normal evaluation
      of bilateral scrotal hydroceles on ultrasonography and subsequently developed the
      abdominal portion during the first year after birth. RESULTS: Four patients
      underwent successful laparoscopic marsupialization of the abdominal component
      before inguinal repair of the ASH. No postoperative complications occurred, and
      no patient required repeat operation. CONCLUSIONS: Laparoscopic marsupialization
      of the abdominal portion of an ASH is a practical surgical alternative that may
      reduce the morbidity of extensive dissection.

PMID- 19118875
TI  - Testosterone gel monotherapy improves sexual function of hypogonadal men mainly
      through restoring erection: evaluation by IIEF score.
AB  - OBJECTIVES: To use the International Index of Erectile Function (IIEF) to
      evaluate the improvement of erectile function and other sexual functions after
      testosterone monotherapy. Testosterone replacement therapy alone was reported to
      be effective for the improvement in sexual function in hypogonadal males.
      However, it is still unclear that which kind of the sexual function is most
      beneficial and to what extent the sexual function could be improved. METHODS: A
      double-blind, randomized, placebo-controlled study was conducted with a treatment
      group (n = 20) and control group (n = 20). Using a critical review of the
      different sexual functional domain scores of the IIEF-15 and the scores of the
      IIEF-5, we evaluated the sexual function of men in hypogonadal status before and
      after 3 months of testosterone gel treatment. Effect size was used to compare the
      drug effects for each sexual functional domain, and the results were confirmed by
      multivariate analysis. RESULTS: A total of 30 men remained at the end of the
      study. After 3 months of testosterone gel therapy for the hypogonadal men, the
      most beneficial effect on sexual function was erectile function, with sexual
      desire and orgasmic satisfaction insignificantly affected. CONCLUSIONS: The
      results of our study have shown that transdermal testosterone gel treatment for
      hypogonadal patients can improve their sexual dysfunction mainly through
      restoring erectile function.

PMID- 19118876
TI  - Perioperative outcomes of elderly patients undergoing laparoscopic renal
      procedures.
AB  - OBJECTIVES: To assess the perioperative outcomes in patients >75 years old to
      better define the role of laparoscopic renal surgery in this expanding segment of
      the U.S. population. The outcomes of elderly patients undergoing laparoscopic
      renal procedures are less well defined than those of younger patients. METHODS:
      We retrospectively reviewed the records of 115 patients >75 years old who had
      undergone laparoscopic renal surgery. The clinical and pathologic features and
      complication rates were analyzed. The patients were substratified according to
      the type of laparoscopic procedure performed and extreme age (>80 years).
      RESULTS: The mean age of our 115 patients was 79.9 years (range 75-91). The
      median estimated blood loss was 200 mL (interquartile range 100-387). The
      transfusion rate was 9.6%. The median length of stay was 4 days (interquartile
      range 3-5). The overall complication rate for the entire cohort was 22.6% and was
      13.7% in those >80 years. The number of patients who experienced a complication
      was 22 (19.1%). Patients with a Charlson comorbidity index >2 were more likely to
      experience a perioperative complication than were patients with a Charlson
      comorbidity index <1 (35% vs 16%; P = .034). CONCLUSIONS: Our data support the
      safety and feasibility of laparoscopic renal procedures in elderly patients.
      Furthermore, this safety extends to patients of advanced age (>80 years). The
      overall complication rates and other perioperative parameters appear to be
      comparable to those in published studies; however, patients with a Charlson
      comorbidity index >2 are at a greater risk of complications in the perioperative
      period.

PMID- 19118877
TI  - Effect of uniform consensus recommendations for PCa screening in older
      population: differential effects and perceptions of healthcare providers and
      patients.
AB  - OBJECTIVES: To develop and distribute consensus recommendations to encourage a
      uniform approach to screening for prostate cancer (PCa) in men >75 years old. We
      also surveyed healthcare providers and men >75 years old to determine whether
      provider attitudes toward continued PCa screening in older men had changed.
      METHODS: We mailed surveys to 2809 Iowa providers to assess their practice toward
      PCa screening and adoption of the consensus recommendations. The results were
      compared with those from a preintervention survey. We also surveyed 9000 Iowa men
      >75 years old to determine whether their providers had changed their screening
      methods. RESULTS: A total of 614 providers (29%) and 1650 men (18%) >75 years old
      responded. Only 48% of providers intended to screen men >75 years old, which was
      reduced from the 63% reported in the preintervention survey. Of the 31% of
      providers who had knowledge of the consensus recommendations, 72% indicated they
      had adopted, or intended to adopt, the recommendations. Of the men >75 years old,
      84% had undergone a prostate-specific antigen test during their life, and 75% had
      continued to be screened after 75 years of age. Also, 54% indicated that their
      provider had discussed screening when they turned 75. Only 18% noted a change in
      their physician's approach to PCa screening after the consensus recommendations
      had been released. CONCLUSIONS: Provider-based education can assist in
      formulating a thoughtful approach to screening and treatment of older men. A
      combination of patient- and provider-directed education could help to encourage
      focused and appropriate PCa screening in older men.

PMID- 19118878
TI  - Effect of dietary changes on urinary oxalate excretion and calcium oxalate
      supersaturation in patients with hyperoxaluric stone formation.
AB  - OBJECTIVES: To test the hypothesis that patients with hyperoxaluria, who modified
      their dietary calcium intake, would reduce their urinary oxalate excretion
      without raising their urinary calcium excretion. Diet is a major factor in
      idiopathic calcium oxalate urolithiasis, yet controversy exists regarding the
      ideal clinical recommendations. Approximately 20% of patients with calcium
      oxalate stone formation have hyperoxaluria (> or = 45 mg oxalate/d). Calcium
      supplements to bind dietary oxalate have been suggested, but clinical evidence of
      this therapy is lacking. METHODS: Of 144 adult patients with stone formation seen
      by a registered dietitian from September 2006 to September 2007, 26 (18%) had
      hyperoxaluria on > or = 1 24-hour urinalyses. Of those with > or = 2 complete 24
      hour collections and whose hyperoxaluria was observed before their last visit
      with the registered dietitian, 22 patients were identified. The patients were
      retrospectively separated into 2 groups according to whether they had been
      advised dietary changes alone (diet group, n = 10) or calcium citrate with meals,
      in addition to the dietary changes (supplement group, n = 12). The mean follow-up
      time was 317 and 266 days for the diet and supplement groups, respectively.
      Statistical comparisons within and between groups were made for urinary risk
      factors. RESULTS: Urinary oxalate excretion decreased from 56 to 43 mg/d and from
      60 to 46 mg/d in the diet and supplement groups, respectively (P = .003 and P =
      .038, respectively). Calcium oxalate supersaturation decreased from 3.48 to 1.83
      and from 2.37 to 1.52 in the diet and supplement groups, respectively (P = .043
      and P = .002, respectively). Urinary calcium excretion did not change in either
      group. CONCLUSIONS: Gastrointestinal binding of oxalate by calcium is an
      effective clinical strategy for hyperoxaluria, whether mediated by calcium
      citrate with meals or by inclusion of calcium-containing foods with meals.

PMID- 19118879
TI  - Removal of an eroded transobturator tape from the bladder using laser
      cystolithotripsy and cystoscopic resection.
AB  - This case presentation describes a unique minimally invasive technique of
      treating transobturator tape erosion into the urinary bladder with calculus
      growth. A 42-year-old woman was admitted for recurrent urinary tract infections,
      9 months after a transobturator tape procedure. Pelvic sonography, followed by
      cystourethroscopy, demonstrated an eroded tape in the bladder with heavy calculus
      growth and diffuse mucosal inflammation. The calculus was fragmented by using
      laser cystolithotripsy, and the tape was excised and removed by using cystoscopic
      resection. Intravesical tape erosion with calculus growth can complicate
      transobturator tape procedures, and is amenable to transurethral laser
      cystolithotripsy and cystoscopic resection.

PMID- 19118880
TI  - Clinical phenotyping of patients with chronic prostatitis/chronic pelvic pain
      syndrome and correlation with symptom severity.
AB  - OBJECTIVES: To propose a clinical phenotype system (urinary, psychosocial, organ
      specific, infection, neurologic/systemic, and tenderness [UPOINT]) to classify
      patients with urologic pelvic pain to help understand the etiology and guide
      therapy. We wished to validate this system in men with chronic pelvic pain
      syndrome (CPPS). CPPS is a heterogeneous syndrome with a variable treatment
      response. METHODS: A total of 90 men with CPPS were retrospectively classified in
      each domain of our UPOINT system and the symptoms were measured using the Chronic
      Prostatitis Symptom Index. RESULTS: The percentage of patients positive for each
      domain was 52%, 34%, 61%, 16%, 37%, and 53% for the urinary, psychosocial, organ
      specific, infection, neurologic/systemic, and tenderness domains, respectively.
      Of the 90 patients, 22% were positive for only 1 domain, and a significant
      stepwise increase was found in the total Chronic Prostatitis Symptom Index score
      as the number of positive domains increased. A symptom duration of >2 years was
      associated with an increase in positive domains (2.9 +/- 0.21 vs 2.3 +/- 0.14, P
      = .01). Comparing the total Chronic Prostatitis Symptom Index score with the
      presence of each domain revealed significantly increased symptoms in patients
      positive for the urinary, psychosocial, organ specific, and neurologic/systemic
      domains. When this analysis was repeated for the pain subscore, the psychosocial,
      neurologic/systemic, and tenderness domains had significantly greater scores.
      Only the psychosocial and neurologic domains influenced the patients' quality of
      life. CONCLUSIONS: Applying the UPOINT system to patients with CPPS can
      discriminate clinical phenotypes, allowing for hypothesis testing for etiology
      and therapy. The number of positive domains correlated with symptom severity and
      a longer duration of symptoms increased the number of positive domains. Because
      each domain has specific targeted therapies, we propose that multimodal therapy
      might best be guided by the UPOINT phenotype.

PMID- 19118881
TI  - Clinical experience and sexual function outcome of patients with priapism treated
      with penile cavernosal-dorsal vein shunt using saphenous vein graft.
AB  - OBJECTIVES: To assess the outcome of new penile cavernosal-dorsal vein shunt
      using a saphenous vein graft. Traditional surgeries for priapism have high
      failure rate and subsequent impotence. METHODS: We reviewed the medical records
      of, and administered a questionnaire and the International Index of Erectile
      Function to, 16 consecutive patients with priapism who had treated with the
      penile cavernosal-dorsal vein shunt from 1997 to 2007. Their age was 15-65 years.
      The duration of ischemic priapism was 32 hours to 8 days. Ten patients had
      previously undergone shunt surgery by other urologists. Of the 16 patients, 5
      returned the questionnaires. RESULTS: Priapism resolved or was improved after
      surgery in all 16 patients. One patient was lost to follow-up. One pediatric
      patient was excluded from the analysis. One patient with nonischemic priapism
      continued to have sexual intercourse. Of the 13 adult patients with ischemic
      priapism and follow-up for < or = 6.5 years, 3 patients had no erection, 1 had
      very little erection, and 9 (69%) had erection. Of the 9 patients with erections
      possible, six had had sexual intercourse (International Index of Erectile
      Function score 32-70) and 3 had not; 1 had a mental disorder, 1 was in prison,
      and for 1, the reason was unknown. After surgery, color Doppler ultrasound
      studies showed a patent shunt in all patients and restoration of cavernosal
      arterial flow in 12 of 13 patients studied. CONCLUSIONS: A penile cavernosal
      dorsal shunt appears effective for priapism. It resulted in priapism resolution
      even in patients who had experienced a previous failed cavernosal-glandular shunt
      or cavernosal-spongiosal shunt, with a high rate of sexual function preservation.

PMID- 19118882
TI  - Prevalence of painful bladder syndrome in older women.
AB  - OBJECTIVES: To examine the prevalence of and symptoms associated with painful
      bladder syndrome (PBS) in a population of older women, utilizing the Nurses'
      Health Study (NHS) cohort. METHODS: In 2004, NHS participants were asked by
      mailed questionnaire, "In the past 10 years, have you experienced bladder or
      pelvic pain associated with urinary symptoms for more than 3 consecutive months?"
      Women who responded "yes" were sent a detailed supplementary questionnaire. A
      severity score was calculated according to information about symptoms and bother
      in the previous 6 months. RESULTS: The PBS screening question was answered by
      67,095 participants. A supplemental questionnaire was sent to all 4005 women who
      answered yes, and 3042 (76%) responded. Symptoms consistent with PBS were
      reported by 1548 respondents (51%), representing 2.3% of the screened cohort. The
      prevalence of PBS was 1.7% in those younger than 65 years and increased
      progressively to 4.0% in women aged 80 years and older (P trend <0.001).
      Severity, based on both symptoms and bother, was mild in 14.8% of women with PBS,
      moderate in 29.0%, and severe in 56.2%. CONCLUSIONS: Painful bladder syndrome is
      a common condition in women. The prevalence of PBS increases with age, and the
      vast majority of women with PBS have moderate or severe symptoms.

PMID- 19118883
TI  - Neonatal imperforate hymen causing obstruction of the urinary tract.
AB  - An imperforate hymen associated with urinary retention, bilateral hydronephrosis,
      and bilateral hydrosalpinx is extremely rare in the neonatal period. We present a
      case of a 2-day-old neonate with a marked interlabial swelling causing urinary
      retention. Imaging revealed hydrometrocolpos, hydrosalpinx, and bilateral
      hydronephrosis. Her symptoms resolved after hymenectomy.

PMID- 19118884
TI  - Accuracy of percutaneous core biopsy in management of small renal masses.
AB  - OBJECTIVES: To determine the sufficiency and accuracy of percutaneous core needle
      renal biopsy in patients with small renal masses (SRMs). METHODS: A retrospective
      chart review was performed on those patients who had undergone image-guided 18
      gauge core renal biopsy of SRMs < or = 4 cm from February 1999 to October 2006.
      The information obtained included the initial biopsy technique, pathologic
      findings, and the clinical outcome. RESULTS: A total of 110 renal biopsies were
      performed for masses < or = 4 cm. The average renal mass size biopsied was 2.7
      cm, with a median of 4 cores taken. Of the 110 biopsies, 100 (90.9%) were
      sufficient for diagnosis and 10 (9.1%) were indeterminate or provided
      insufficient tissue. Of the 100 diagnostic biopsies, 65% were interpreted as
      malignant and 35% as benign. There were 8 complications (7.2%), with 2
      postprocedural hematomas (1.8%). Thirty-four patients underwent surgical
      extirpation; the ultimate histopathologic accuracy of biopsy compared with the
      final surgical pathologic finding was 100% (34/34) in these patients.
      CONCLUSIONS: Image-guided core needle biopsy is highly accurate in SRMs, and more
      than one third of these lesions will be benign. With a low complication rate,
      core biopsy provides a histopathologic diagnosis that aids in decision-making for
      the growing number of incidentally detected SRMs.

PMID- 19118885
TI  - Antitumor effects of an imidazoquinoline in renal cell carcinoma.
AB  - OBJECTIVES: To evaluate the effects of imidazoquinolines in renal cell carcinoma
      (RCC). METHODS: In vitro experiments were carried out using mouse (RENCA) and
      human (CAKI-1, CAKI-2, and A-498) RCC cell lines. Toll-like receptor-7 (TLR7)
      expression was assessed by Western blot. We determined the ability of
      imidazoquinolines to induce apoptosis and inhibit cell viability in vitro. For in
      vivo experiments, RENCA cells were injected into the tail vein of syngeneic mice.
      One week after injection, mice were given oral imidazoquinoline or placebo for 14
      days. Mice were then sacrificed, and lungs were inspected for tumor nodules.
      Immunohistochemical staining was used to assess apoptosis in vivo. RESULTS: Toll
      like receptor-7 was expressed in all cell lines tested, with RENCA cells showing
      the highest level of expression. Imidazoquinolines inhibited in vitro cell
      viability of RENCA, CAKI-2, and A-498 cell lines in a time-dependent manner.
      Viability of CAKI-1 was not inhibited significantly. Apoptosis induction was
      pronounced in RENCA cells treated with imidazoquinoline. Compared with placebo,
      oral imidazoquinoline significantly reduced the number of pulmonary metastasis
      and increased cell death in vivo. CONCLUSIONS: Imidazoquinolines inhibit cell
      viability and cause deoxyribonucleic acid fragmentation leading to apoptosis in
      RCC cell lines, potentially working through the TLR7 expressed by RCC cell lines.
      Preliminary data from a mouse model of metastatic RCC also suggest antitumor
      effects and induction of apoptosis in vivo.

PMID- 19118886
TI  - Laparoscopic orchiectomy and subsequent internal ring closure for extra-abdominal
      testicular nubbin in children.
AB  - OBJECTIVES: To present our preliminary experience with laparoscopic groin
      exploration and subsequent laparoscopic orchiectomy and internal ring closure for
      testicular nubbin in children and discuss the usefulness of our new treatment
      strategy. The advantages of laparoscopic orchiopexy for intra-abdominal testis
      are the ability to start treatment as soon as a diagnosis has been made and to
      permit minimally invasive surgery. These advantages can apply to laparoscopic
      orchiectomy for a testicular nubbin. METHODS: A total of 6 boys with a testicular
      nubbin (age range 14-76 months, mean age 27.3 months) underwent laparoscopic
      orchiectomy at our institution from June 2007 to June 2008. We opened the
      posterior parietal peritoneum by incising the peritoneum lateral to the spermatic
      vessel, distal to the patent processus vaginalis and medial and distal to the vas
      deferens (laparoscopic groin exploration). Next, the testicular nubbin was pulled
      out into the abdomen and was then removed laparoscopically after identification
      and division of the gubernaculums. Finally, laparoscopic complete internal ring
      and peritoneal defect closure was performed with 5-0 Vicryl suture. RESULTS: The
      average operative time, including the diagnostic time, was 64 minutes. No
      intraoperative or postoperative complications developed. In 1 boy with a
      testicular nubbin, an open processus vaginalis was present, and simultaneous
      laparoscopic transection of the processus vaginalis and subsequent internal ring
      closure were performed. CONCLUSIONS: All patients with a testicular nubbin could
      be treated as soon as the diagnosis was made using only laparoscopic management,
      with minimal morbidity and good short-term results.

PMID- 19118887
TI  - Effect of aberrant vasculature during cryosurgery for prostate cancer.
AB  - Efficacy of cryosurgery for treatment of prostate cancer is based on completely
      freezing the prostate and all malignant tissues. The image from this patient
      demonstrates aberrant periprostatic vascular anatomy featuring two vessels that
      created a "heat sink" that overcame the outer extension of the ice ball,
      resulting in potential incomplete freeze in the area of the vessels.

PMID- 19118888
TI  - Stage II uterine papillary serous carcinoma: Carboplatin/paclitaxel chemotherapy
      improves recurrence and survival outcomes.
AB  - OBJECTIVES: To determine recurrence patterns and survival outcomes of stage II
      uterine papillary serous carcinoma (UPSC) patients treated by various modalities
      with an emphasis on carboplatin/paclitaxel-based chemotherapy (CT)+/-radiotherapy
      (RT). METHODS: A retrospective, multi-institution study of women with stage II
      UPSC diagnosed from 1992 to 2006 was performed. All patients underwent
      comprehensive surgical staging. Treatment included observation (OBS), RT (vaginal
      brachytherapy, whole pelvic and/or whole abdominal therapy), or >or=3 cycles
      carboplatin/paclitaxel alone or with RT. Recurrence and survival outcomes were
      determined. RESULTS: We identified 55 subjects: 10 treated with OBS, 26 with RT
      alone and 19 with CT+/-RT. After a median follow-up of 33 mos (range, 10-119), 20
      recurrences (36%) were observed. There was an overall difference in recurrence
      based upon treatment (p=.013). Specifically, all CT+/-RT treated patients had a
      lower risk of recurrence (11%) compared to patients treated by RT alone (50%) or
      OBS (50%). No patients treated with both CT+RT (n=12) experienced a recurrence.
      Treatment with CT was also associated with a decreased risk of recurrence on
      multivariate analysis (p=.015). Most recurrences were extra-pelvic (70%),
      occurred within 2 years (85%) and were not salvageable (84%). Five-year
      progression-free survival was 86% in chemotherapy-treated patients versus 41% in
      those not receiving chemotherapy (p=.010); overall survival was 88% in
      chemotherapy-treated patients versus 64% in those not receiving chemotherapy
      (p=.115). CONCLUSIONS: Stage II UPSC patients have a significant risk for
      unsalvageable, extra-pelvic recurrence. However, treatment with platinum/taxane
      therapy+/-RT appears to reduce this risk and is associated with improved
      progression free survival outcomes.

PMID- 19118889
TI  - In vitro production of cattlexbuffalo hybrid embryos using cattle oocytes and
      African buffalo (Syncerus caffer caffer) epididymal sperm.
AB  - Interspecies hybridization of bovids occurs between domestic cattle and at least
      three other species; American bison (Bison bison), yak (Bos grunniens) and
      banteng (Bos banteng). Birth of a cattlexbuffalo (Bubalus bubalis) hybrid has
      reportedly occurred in Russia and in China, but these reports were not
      authenticated. Such hybrids could be important in improving livestock production
      and management of diseases that impede production in tropical Africa. This study
      investigated hybridization between cattle and its closest African wild bovid
      relative, the African buffalo (Syncerus caffer caffer). In an attempt to produce
      cattlexbuffalo hybrid embryos in vitro, matured cattle oocytes were subjected to
      a standard in vitro fertilization (IVF) procedure with either homologous cattle
      (n=1166 oocytes) or heterologous African buffalo (n=1202 oocytes) frozen-thawed
      epididymal sperm. After IVF, 67.2% of the oocytes inseminated with the homologous
      cattle sperm cleaved. In contrast, fertilization with buffalo sperm resulted in
      only a 4.6% cleavage rate. The cleavage intervals were also slower in hybrid
      embryos than in the IVF-derived cattle embryos. Of the cleaved homologous cattle
      embryos 52.2% progressed to the morula stage compared with 12.7% for the buffalo
      hybrid embryos. No hybrid embryos developed beyond the early morula stage, while
      40.1% of the cleaved cattlexcattle embryos developed to the blastocyst stage.
      Transfer of buffalo hybrid IVF embryos to domestic cattle surrogates resulted in
      no pregnancies at 60 days post-transfer. This study indicates that interspecies
      fertilization of cattle oocytes with African buffalo epididymal sperm can occur
      in vitro, and that a barrier to hybridization occurs in the early stages of
      embryonic development. Chromosomal disparity is likely the cause of the
      fertilization abnormalities, abnormal development and subsequent arrest impairing
      the formation of hybrid embryos beyond the early morula stage. Transfer of the
      buffalo hybrid embryos did not rescue the embryos from development arrest.

PMID- 19118890
TI  - A sensitive and efficient detection method for bovine viral diarrhea virus (BVDV)
      in single preimplantation bovine embryos.
AB  - The objective was to develop a method to accurately and efficiently detect minute
      amounts of bovine viral diarrhea virus (BVDV) associated with a single embryo.
      There are two major challenges for BVDV detection in a single embryo: the test
      sensitivity and the efficiency of viral molecule recovery. These become even more
      critical when attempts are made to detect BVDV infections that occurred
      naturally, not through artificial exposure of the embryos to high affinity BVDV
      strains. We have developed a one-step sample preparation method that has
      increased the viral molecule recovery rate compared to the standard RNA isolation
      procedure by 7-100-fold. Instead of using the traditional virus exposure
      approach, we generated BVDV positive embryos via somatic cell nuclear transfer
      (SCNT) technology using BVDV positive donor cells. By combining the highly
      efficient sample preparation procedure with a sensitive one-step, real-time PCR
      system, we have developed a sensitive test that allows detection of as low as two
      copies of BVDV in a single embryo. This method will allow systematic risk
      assessment for BVDV transmission during in vitro embryo production via IVF or
      SCNT procedures.

PMID- 19118891
TI  - Correlation of anisotropic cell behaviors with topographic aspect ratio.
AB  - In this study, we have used nanoimprinting to create a range of micro- and
      nanoscale gratings, or their combination, in bulk polystyrene plates to
      investigate anisotropic cell behaviors of human dermal fibroblasts with respect
      to the aspect ratio (depth/width) of gratings. The depth and width of the
      polystyrene gratings both show strong effects individually on cell alignment and
      elongation that are qualitatively similar to the results of other studies.
      However, consistent quantitative comparison of these individual parameters with
      different studies is complicated by the diversity of combinations of width and
      depth that have been tested. Instead, the aspect ratio of the gratings as a
      unified description of grating topography is a more consistent parameter to
      interpret topographic dependence of cell morphology. Both cell alignment and
      elongation increase with increasing aspect ratio, and even a shallow grating
      (aspect ratio of approximately 0.05) is sufficient to induce 80% cell alignment.
      Re-plotting data recently published by other groups vs. aspect ratio shows a
      similar dependence, despite differences in cell types and surface structures.
      This consistency indicates that aspect ratio is a general factor to characterize
      cell behaviors. The relationship of cell elongation and alignment with
      topographic aspect ratio is interpreted in terms of the theory of contact
      guidance. This model provides simplicity and flexibility in geometry design for
      devices and materials that interface with cells.

PMID- 19118892
TI  - The role of the silicatein-alpha interactor silintaphin-1 in biomimetic
      biomineralization.
AB  - Biosilicification in sponges is initiated by formation of proteinaceous
      filaments, predominantly consisting of silicateins. Silicateins enzymatically
      catalyze condensation of silica nanospheres, resulting in symmetric skeletal
      elements (spicules). In order to create tailored biosilica structures in
      biomimetic approaches it is mandatory to elucidate proteins that are fundamental
      for the assembly of filaments. Silintaphin-1 is a core component of modularized
      filaments and also part of a spicule-enfolding layer. It bears no resemblance to
      other proteins, except for the presence of an interaction domain that is
      fundamental for its function as scaffold/template. In the presence of silicatein
      silintaphin-1 facilitates the formation of in vitro filaments. Also, it directs
      the assembly of gamma-Fe(2)O(3) nanoparticles and surface-immobilized silicatein
      to rod-like biocomposites, synthetic spicules. Thus, silintaphin-1 will
      contribute to biomimetic approaches that pursue a controlled formation of
      patterned biosilica-based materials. Its combination with gamma-Fe(2)O(3)
      nanoparticles and immobilized silicatein will furthermore inspire future
      biomedical applications and clinical diagnostics.

PMID- 19118893
TI  - The influence of laminin-derived peptides conjugated to Lys-capped PLLA on
      neonatal mouse cerebellum C17.2 stem cells.
AB  - Chemical guiding cues are being exploited to stimulate neuron adhesion and
      neurite outgrowth. In this study, an amino-functioned PLLA, lysine-capped PLLA [K
      (CH(2))(n)-PLLA (n=2, 5, 8)], was synthesized with different length of linking
      spaces between lysine molecule and PLLA backbone. Drop-cast films were fabricated
      from K-(CH(2))(n)-PLLA/PLLA blends (10/90, w/w) and amino groups were detected on
      the surfaces of the resultant films. More amine groups were detected on the
      surface and the hydrophilicity of the films was obviously improved by annealing
      the films in water. The representative atomic force microscopy (AFM) images
      indicated that incorporation of lysine-capped PLLA into PLLA matrix increased the
      roughness of the films and resulted in a phase separation with distinct two nano
      domains which may correspond to the hydrophilic and hydrophobic domains.
      Furthermore, the laminin-derived peptides, CYIGSR (Cys-Tyr-Ile-Gly-Ser-Arg) and
      CSIKVAV (Cys-Ser-Ile-Lys-Val-Ala-Val), were jointly tethered to the amine groups
      of lysine-capped PLLA by a linking reagent sulfo-succinimidyl 4-(N
      maleimidomethyl) cyclohexane-1-carboxylate (Sulfo-SMCC). The neonatal mouse
      cerebellum C17.2 stem cells were seeded on the peptides-grafted K-(CH(2))(n)
      PLLA/PLLA (n=2, 5, 8) films and pure PLLA films were used as controls. Improved
      viability and longer neurites were obtained on the peptide-grafted films than
      PLLA film over the cultivation period, especially for K-(CH(2))(5)-PLLA/PLLA,
      which had the highest peptide density of 0.28+/-0.03 microg/cm(2). This study
      highlights the potential of using the lysine-capped PLLA with laminin-derived
      peptides for promoting nerve regeneration.

PMID- 19118894
TI  - Inhibition of titanium particle-induced osteoclastogenesis through inactivation
      of NFATc1 by VIVIT peptide.
AB  - Osteoclastogenesis induced by particulate wear debris is a major pathological
      factor contributing to periprosthetic osteolysis. Although the nuclear factor of
      activated T cells c1 (NFATc1) is known to be involved in osteoclast
      differentiation, its effect on osteoclastogenesis in response to wear particles
      remains unclear. In the present study, we investigated the role of NFATc1 in the
      regulation of osteoclast differentiation from bone marrow macrophages (BMMs)
      stimulated with titanium (Ti) particles. The results showed that Ti particles
      could stimulate BMMs to produce proinflammatory cytokines (tumor necrosis factor
      (TNF)-alpha, interleukin (IL)-1beta, and IL-6) and differentiate into
      multinucleated osteoclasts in the presence of receptor activator of nuclear
      factor-kappaB ligand (RANKL). NFATc1 was expressed in BMMs and multinucleated
      cells cultured with Ti particles and RANKL. Inactivation of NFATc1 by 11R-VIVIT
      peptide potently impeded the Ti particle-induced osteoclastogenesis. 11R-VIVIT
      peptide does not have toxic effect on BMMs. Based on these data, we conclude that
      inactivation of NFATc1 by VIVIT peptide would provide a promising therapeutic
      target for the treatment of periprosthetic osteolysis.

PMID- 19118895
TI  - The behavior of endothelial cells on polyurethane nanocomposites and the
      associated signaling pathways.
AB  - A series of nanocomposites from polyurethane (PU) incorporated with various low
      concentrations (17.4-174 ppm) of gold nanoparticles (approximately 5 nm) (denoted
      "PU-Au") were used as a model system to study the mechanisms that influenced
      endothelial cell (EC) migration on biomaterial surfaces. The migration rate of
      ECs on the PU-Au nanocomposites was determined by a real-time image system. It
      was found that ECs had the highest migration rate on the nanocomposite containing
      43.5 ppm of gold ("PU-Au 43.5 ppm"). The high EC migration rate was associated
      with increased levels of endothelial nitric oxide synthase (eNOS) and
      phosphorylated-Akt (p-Akt) expressed by ECs cultured on PU-Au. The inductions of
      both eNOS and p-Akt on PU-Au were abolished by the addition of LY294002 (PI3K
      inhibitor), suggesting that these cellular events may be regulated through the
      PI3K signaling pathway. Using a biotinylated VEGF-165 that recognizes VEGF
      receptors and by FACS analysis, slightly higher expression of VEGF receptors for
      ECs on PU-Au was also demonstrated. Phalloidin staining showed that actin
      appeared as a circumferential band surrounding each cell on tissue culture
      polystyrene, whereas on PU-Au, especially on PU-Au 43.5 ppm, the cells had their
      margin spread out and extend processes with stress fibers in the protruding
      lamellipodia. Moreover, the higher EC migration rate on PU-Au 43.5 ppm was
      suppressed by LY294002. The higher protein expression of focal adhesion kinase
      (FAK) on PU-Au 43.5 ppm was observed in FAK-GFP transfected ECs. It was concluded
      that PU-Au nanocomposites activated FAK and the PI3K/Akt signaling pathway in
      ECs, leading to proliferation and migration of ECs on these surfaces.

PMID- 19118896
TI  - Gabor Than Award Lecture 2008: pre-eclampsia - from placental oxidative stress to
      maternal endothelial dysfunction.
AB  - Pre-eclampsia is the most important complication of human pregnancy worldwide and
      a major contributor to maternal and fetal morbidity and mortality. Strong
      evidence exists that generation of placental oxidative stress, secondary to
      deficient spiral artery remodelling, is a key intermediary event, triggering the
      secretion of a mixture of placental factors that culminate in an enhanced
      maternal inflammatory response. Reactive oxygen species (ROS) have been
      recognised as secondary messengers in intracellular signalling cascades.
      Experiments studying placental ischaemia-reperfusion in vitro or in vivo during
      labour provide strong evidence suggesting that oxidative stress and ROS
      production can activate downstream stress-signalling pathways, p38 and SAPK/JNK
      MAPK, and the pro-inflammatory NF-kappaB signalling pathway, culminating in the
      release of inflammatory mediators, apoptotic debris, anti-angiogenic factors and
      other mediators, which then stimulate a maternal inflammatory reaction that
      manifests in endothelial dysfunction and the symptoms of pre-eclampsia. Addition
      of anti-oxidants or blocking the stress or inflammatory pathways in vitro
      attenuates these effects and opens possibilities for therapeutic intervention.

PMID- 19118897
TI  - Validation of a new three-color fluorescence in situ hybridization (FISH) method
      to detect CHIC2 deletion, FIP1L1/PDGFRA fusion and PDGFRA translocations.
AB  - The PDGRFA locus has become a gene of interest based on mutational activation in
      various myeloid neoplasms and the availability of targeted therapies (i.e.,
      imatinib mesylate) to its overexpression. We studied a new FISH method to detect
      CHIC2 deletion, FIP1L1/PDGFRA fusion and PDGFRA translocation in patients with
      myeloid neoplasms associated with eosinophilia. A total of 46 specimens were
      studied, including 15 from patients with a CHIC2 abnormality and six patients
      with an abnormality involving PDGFRA. Our results revealed this new FISH assay
      accurately detects these abnormalities and will be a useful clinical test for
      patients with myeloid neoplasms and eosinophilia.

PMID- 19118898
TI  - sFRP1 promoter methylation is associated with persistent Philadelphia chromosome
      in chronic myeloid leukemia.
AB  - Epigenetic silencing of sFRP genes has been shown to lead to constitutive
      activation of the canonical Wnt-signaling pathway. The first description of
      deregulated Wnt-signaling activation in a hematological malignancy was reported
      in chronic myeloid leukemia (CML). To investigate whether epigenetic silencing of
      sFRP is responsible for the observed Wnt activation in CML, we studied the
      methylation and mutational status of the sFRP1 promoter in 48 chronic phase CML
      patients. Of the 48 CML patients 41 were shown to be unmethylated, 6 patients
      hemi-methylated and 1 patient fully methylated at the sFRP1 promoter. Albeit
      observed infrequently in chronic phase CML, sFRP1 promoter methylation correlated
      with primary cytogenetic resistance to imatinib mesylate. sFRP1 promoter
      methylation may indicate a genetically more unstable form of disease resistant to
      therapy and provide a key biological difference in therapy resistant patients, in
      addition to a possible mechanism for the observed activation of canonical Wnt
      signaling in CML.

PMID- 19118899
TI  - Karyopherin alpha 1 is a putative substrate of the RAG1 ubiquitin ligase.
AB  - The RAG1 recombinase, which participates in DNA manipulation during rearrangement
      of antigen receptor genes in developing immune cells, possesses ubiquitin ligase
      activity. The nuclear transport protein karyopherin alpha 1 (KPNA1) binds to RAG1
      upstream of its ubiquitin ligase domain, but this interaction is not required for
      nuclear localization of RAG1. We found that the isolated ubiquitin ligase domain
      of RAG1 (amino acids 218-389) promoted ubiquitylation of purified KPNA1. While
      RAG1 auto-ubiquitylation is dependent on the ubiquitin conjugating enzyme CDC34,
      ubiquitylation of KPNA1 was best supported by UbcH2/Rad6 and UbcH5a.
      Ubiquitylation of KPNA1 required the lysine/arginine-rich region spanning RAG1
      amino acids 218-263 upstream of the RAG1 ubiquitin ligase domain, but RAG1 was
      still able to undergo auto-ubiquitylation in this region even in the presence of
      KPNA1. This is the first putative substrate identified for the RAG1 ubiquitin
      ligase, and to our knowledge it is the first reported case of ubiquitylation of
      KPNA1.

PMID- 19118900
TI  - PAX2 oncogene negatively regulates the expression of the host defense peptide
      human beta defensin-1 in prostate cancer.
AB  - Human beta defensin-1 (hBD1) is a component of the immune system which links the
      innate and adaptive immune responses. We have demonstrated that hBD1 induces
      rapid cytolysis of prostate cancer cells and that it may also possess tumor
      suppressive abilities. In addition, there is a high frequency of cancer-specific
      loss of hBD1 expression which further suggests its potential role in tumor
      progression. However, the factors responsible for the loss of hBD1 expression are
      not known. PAX2, a transcriptional regulator normally expressed during early
      development, has been implicated as an oncogene in carcinomas of the kidney,
      prostate, breast and ovary. It is known that expression of PAX2 in these tumor
      cells mediates the evasion of cell death through the suppression of cell death
      pathways involving the p53 tumor suppressor. However, we have demonstrated that
      knock-down of PAX2 expression results in cell death independent of p53 status,
      thus suggesting that additional cell death pathways are negatively regulated by
      PAX2. Here we describe a novel pathway in which PAX2 represses hBD1 expression
      through binding of the PAX2 homeodomain to the hBD1 promoter. Furthermore, knock
      down of PAX2 expression results in the re-expression of hBD1, and subsequently
      prostate cancer cell death. These findings are the first to demonstrate that the
      PAX2 oncogene suppresses hBD1 expression in cancer and further implicate PAX2 as
      a novel therapeutic target for prostate cancer treatment.

PMID- 19118901
TI  - Rac1 regulates peptidoglycan-induced nuclear factor-kappaB activation and
      cyclooxygenase-2 expression in RAW 264.7 macrophages by activating the
      phosphatidylinositol 3-kinase/Akt pathway.
AB  - Previously, we found that peptidoglycan (PGN), a cell wall component of the gram
      positive bacterium Staphylococcus aureus, may activate the Ras/Raf
      1/extracellular signal-regulated kinase (ERK) pathway, which in turn initiates
      IkappaB kinases alpha/beta (IKKalpha/beta) and nuclear factor-kappaB (NF-kappaB)
      activation, and ultimately induces cyclooxygenase-2 (COX-2) expression in RAW
      264.7 macrophages. In this study, we further investigated the roles of Rac1,
      phosphatidylinositol 3-kinase (PI3K), and Akt in PGN-induced NF-kappaB activation
      and COX-2 expression in RAW 264.7 macrophages. PGN-induced COX-2 expression was
      attenuated by a Rac1 dominant negative mutant (RacN17), PI3K inhibitors
      (wortmannin and LY 294002), and an Akt inhibitor (1L-6-hydroxymethyl-chiro
      inositol2-[(R)-2-O-methyl-3-O-octadecylcarbonate]). PGN-induced PGE(2) release
      was also inhibited by RacN17. Treatment of RAW 264.7 macrophages with PGN caused
      the activation of Rac and Akt. PGN-induced Akt activation was inhibited by
      RacN17, LY 294002, and the Akt inhibitor. Stimulation of RAW 264.7 macrophages
      with PGN resulted in an increase in IKKalpha/beta phosphorylation and p65 Ser536
      phosphorylation; these effects were inhibited by RacN17, LY 294002, an Akt
      inhibitor, and an Akt dominant negative mutant (AktDN). The PGN-induced increases
      in kappaB-luciferase activity were also inhibited by RacN17, wortmannin, LY
      294002, an Akt inhibitor, and AktDN. Treatment of macrophages with PGN induced
      the recruitment of p85alpha and Rac1 to Toll-like receptor 2 (TLR2) in a time
      dependent manner. These results indicate that PGN may activate the Rac1/PI3K/Akt
      pathway through the recruitment of p85alpha and Rac1 to TLR2 to mediate
      IKKalpha/beta activation and p65 phosphorylation, which in turn induces NF-kappaB
      transactivation, and ultimately causes COX-2 expression in RAW 264.7 macrophages.

PMID- 19118902
TI  - Dicer is regulated by cellular stresses and interferons.
AB  - The generation of microRNAs is dependent on the RNase III enzyme Dicer, the
      levels of which vary in different normal cells and in disease states. We
      demonstrate that Dicer protein expression in JAR trophoblast cells, and several
      other cell types, was inhibited by multiple stresses including reactive oxygen
      species, phorbol esters and the Ras oncogene. Additionally, double-stranded RNA
      and Type I interferons repress Dicer protein in contrast to IFN-gamma which
      induces Dicer. The effects of stresses and interferons are primarily post
      transcriptional. The findings suggest that Dicer is a stress response component
      and identifies interferons as potentially important regulators of Dicer
      expression.

PMID- 19118903
TI  - Non-canonical anchor motif peptides bound to MHC class I induce cellular
      responses.
AB  - The major histocompatibility complex (MHC) on the surface of antigen presenting
      cells functions to display peptides to the T cell receptor (TCR). Recognition of
      peptide-MHC by T cells initiates a cascade of signals, which results in the
      initiation of a T cell dependent immune response. An understanding of how
      peptides bind to MHC molecules is important for determining the structural basis
      for T cell dependent immune responses and facilitates the structure-based design
      of peptides as candidate vaccines to elicit a specific immune response. To date,
      crystal structures, immunogenicity and in vivo biological relevance have mainly
      been characterized for high affinity peptide-MHC interactions. From the crystal
      structures of numerous peptide-MHC complexes it became apparent what canonical
      sequence features were required for high affinity binding, which led to the
      ability to predict in most instances peptides with high affinity for MHC. We
      previously identified the crystal structures of non-canonical peptides in complex
      with MHC class I (one bound with low affinity and the other with high affinity,
      but utilizing novel peptide anchors and MHC pockets). It is becoming increasingly
      evident that other non-canonical peptides can also bind, such as long-, short-
      and glyco-peptides. However, the in vivo role of non-canonical peptides is not
      clear and we present here the immunogenicity of two non-canonical peptides and
      their affinity when bound to MHC class I, H2K(b). Comparison of the three
      dimensional structures in complex with MHC suggests major differences in hydrogen
      bonding patterns with H2K(b), despite sharing similar binding modes, which may
      account for the differences in affinity and immunogenicity. These studies provide
      further evidence for the diverse range of peptide ligands that can bind to MHC
      and be recognized by the TCR, which will facilitate approaches to peptide-based
      vaccine design.

PMID- 19118904
TI  - Comparison of sleep/wake parameters for self-monitoring bipolar disorder.
AB  - BACKGROUND: Psychosocial interventions may teach patients with bipolar disorder
      to successfully detect warning signs of relapse. These interventions often
      include ongoing self-monitoring of sleep. We previously reported that a change in
      sleep duration (sleep plus bedrest) of >3 h may indicate that a mood change is
      imminent. This analysis further investigated whether sleep duration, sleep onset
      or sleep offset was the most useful sleep/wake parameter to monitor for an
      oncoming mood change. METHODS: 101 adult outpatients receiving treatment as usual
      recorded mood, sleep and medications every day on a home computer for a mean of
      265+/-103 days. A daily time series of mood, sleep duration (sleep plus bedrest),
      sleep onset and sleep offset was constructed for each patient. After applying an
      ARIMA (0,1,1) filter, a cross correlation function was used to analyze the
      temporal relationship between the residuals for lags of +/-7 days. RESULTS: Less
      frequent significant correlations were found between a change in either sleep
      onset or sleep offset and mood, than between sleep duration and mood. Patients
      with a significant correlation between sleep duration and mood included 86% of
      those with a significant correlation between sleep onset or sleep offset and
      mood. Mean sleep duration when euthymic was long (> or =8 h in 89% of patients, >
      or =9 h in 51% of patients). LIMITATIONS: Self-reported data, naturalistic study,
      and computer access required. CONCLUSIONS: Self-monitoring of sleep duration is
      recommended for patients with bipolar disorder. Better understanding of the long
      sleep duration of euthymic patients is required.

PMID- 19118905
TI  - Molecular characterization of chicken prion proteins by C-terminal-specific
      monoclonal antibodies.
AB  - We obtained seven monoclonal antibodies (mAbs) against chicken cellular prion
      protein (ChPrP(C)) by immunizing BALB/c mice with recombinant prion protein
      (rChPrP). Of the seven mAbs, two mAbs (6 and 26) could recognize rChPrP, but not
      ChPrP(C), in chicken brain lysate via Western blot (WB) analysis. Three C
      terminal linear epitopes (AAANQTEVEM, RWWS and SPVPQD) were identified in ChPrP
      amino acids by pepspot analysis with five mAbs. The mAbs recognizing the C
      terminal epitopes in ChPrP(C) predominantly reacted with the N-terminal truncated
      ChPrP(C) in WB analysis, which differed from the reaction with N-terminal
      proline/glycine-rich repeats recognizing rabbit polyclonal antibody. These mAbs
      will soon be available as a useful tool to characterize the biology of ChPrP(C)
      in birds.

PMID- 19118906
TI  - Effect of porcine circovirus type 2 infection and replication on activated
      porcine peripheral blood mononuclear cells in vitro.
AB  - The goal of this study was to examine the effect of porcine circovirus type 2
      (PCV2) infection and replication on peripheral blood mononuclear cells (PBMCs) in
      the presence of mitogens, concanavalin A (ConA) or pokeweed mitogen (PWM) in
      vitro. The level of PCV2 replication and the impact of infection on PBMC
      proliferation, viability and the level of apoptosis in the presence or absence of
      mitogen stimulation were assessed. Mitogen stimulation increased viral
      replication in PBMCs as measured by the amount of spliced capsid mRNA (Cap mRNA).
      However, cell proliferation alone had no significant impact on PCV2 replication
      as the level of Cap mRNA in ConA or PWM stimulated PBMCs was not increased in
      proliferating cells compared to non-proliferating cells. No significant
      differences were observed in the level of PCV2 replication product in PBMCs
      stimulated with ConA for 12, 36, and 72 h prior to infection. Infection with PCV2
      did not affect the ability of PBMCs to proliferate in response to ConA or PWM
      stimulation in vitro. Increased apoptosis was associated with PCV2 infection in
      PWM stimulated PBMCs. Interestingly, a significantly lower apoptotic index was
      observed in PCV2 infected PBMCs compared to mock-infected cells in the absence of
      mitogens. This study determined that the rate of PCV2 replication increases with
      cell stimulation and apoptosis is increased following PCV2 infection under
      certain stimulation conditions. These results further suggest that PCV2 requires
      a specific stimulation or trigger for increased viral replication, which is
      independent of cell proliferation.

PMID- 19118907
TI  - Tissue concentrations of 4-HNE in the black walnut extract model of laminitis:
      indication of oxidant stress in affected laminae.
AB  - In the septic horse prone to laminitis, a similar activation of the innate immune
      system appears to occur as reported in the septic human prone to organ failure.
      Because oxidant injury plays a central role in organ failure occurring due to an
      overzealous innate immune response in human sepsis, this study was performed to
      determine whether there was evidence of oxidant stress in the laminar tissue in
      the early stages of laminitis. 4-Hydroxy-2-nonenal (4-HNE), a lipid aldehyde that
      forms due to lipid peroxidation occurring during episodes of oxidant stress,
      readily forms adducts with cellular proteins; these adducts can be assessed as a
      marker of oxidant stress in the form of lipid peroxidation. In this study, a slot
      blot technique was used to assess 4-HNE adduct concentrations in the laminae,
      lung, liver, and intestinal tract in the black walnut extract (BWE) model of
      laminitis. Significant increases in laminar 4-HNE adduct concentrations were
      identified at two early stages in the BWE model, in the absence of such changes
      in the other tissues. These data indicate that oxidant stress may play an
      important role in the laminar failure in laminitis, and further support the
      concept that a poor antioxidant response in the laminae relative to other equine
      tissues may be responsible for failure of the laminae in the septic horse. In
      contrast, tissues such as the lung and liver that undergo oxidant injury in human
      sepsis appear to be relatively protected in horses.

PMID- 19118908
TI  - Old patients in intensive care unit (ICU): what decisions to make?
AB  - This report is aimed at identifying and suggesting a decision-making approach to
      handle old patients in ICUs in the light of current epidemiological findings and
      literature. We reviewed the data provided by the GIVITI network on 107,459
      patients admitted to 150 Italian ICUs between 2000 and 2005; patients were
      divided into age groups (18-65 years: group I; 66-75 years: group II; 76-85
      years: group III; > or =85 years: group IV). Comorbidities were recorded on
      admission in all groups [I (62.2%), II (92.2%), III (94.9%) and IV (94.5%),
      respectively]. Therapeutic means were virtually applied in the same way to all
      groups under examination [I (82.1%), II (83.9%), III (85.9%) and IV (83.5%),
      respectively]. Mortality in ICU was higher in group IV (27.2%), followed by
      groups III (24.3%), II (19.1%) and I (13.2%). The multivariate logistic
      regression analysis of GIVITI and some reviewed studies suggest that age is an
      independent mortality factor; however, current literature is controversial. The
      choice of admitting and treating old patients in ICUs should result from a
      balance between clinical and ethical factors.

PMID- 19118909
TI  - Relationship between -592A/C polymorphism of interleukin-10 (IL-10) gene and risk
      of early carotid atherosclerosis.

PMID- 19118911
TI  - Characteristics of undiagnosed diabetes mellitus in a population undergoing
      health screening in Japan: target populations for efficient screening.
AB  - AIMS: To estimate the prevalence of undiagnosed diabetes mellitus and its
      relationship with various risk factors in a population undergoing health
      screening in Japan. METHODS: Oral glucose tolerance tests were carried out in a
      total sample of 14,674 Japanese subjects undergoing health screening, aged 20-83
      years and without known diabetes. The prevalence of glucose tolerance categories
      (1999 WHO criteria) was adjusted for sample probabilities. The optimal FPG cut
      off point for screening diabetes was estimated using ROC curve analysis for the
      continuous value of FPG corresponding to a 2-h PG of 200 mg/dl. The number needed
      to screen (NNTS) to identify one person with undiagnosed diabetes with various
      risk factors was estimated using the following equation: the number of
      undiagnosed diabetic plus nondiabetic subjects/the number of undiagnosed diabetic
      subjects. RESULTS: The prevalence of undiagnosed diabetes among men and women was
      6.4% (NNTS 15.7) and 3.2% (NNTS 31.7), respectively. The optimal FPG cut-off
      point for screening diabetes among men and women was 105 and 106 mg/dl,
      respectively. NNTS was lower in individuals with more risk factors, e.g. aging (>
      or =50), BMI (> or =25), hypertension (SBP> or =140 mmHg and/or DBP> or =90 mmHg)
      and dyslipidemia (TC> or =220 and/or HDL-C<40 and/or TG> or =150 mg/dl),
      resulting in the lowest NNTS in individuals having all four risk factors among
      men (6.1) and women (6.7), respectively. CONCLUSIONS: In Japan, screening for
      diabetes may be more efficient among individuals having an FPG of more than 105
      106 mg/dl and with more risk factors, especially in men.

PMID- 19118910
TI  - Telmisartan improves vascular function independently of metabolic and
      antihypertensive effects in hypertensive subjects with impaired glucose
      tolerance.
AB  - BACKGROUND: Hypertensive patients with IGT have increased risk for cardiovascular
      disease and progression to diabetes mellitus. Clinical trials suggest that the
      ARB telmisartan uniquely possesses PPARgamma agonistic properties and improves
      insulin resistance as well as vascular endothelial dysfunction. The aim of the
      present study was to compare vascular effects of telmisartan and losartan in
      relation to their metabolic and antihypertensive effects in hypertensive patients
      with IGT. MATERIALS AND METHODS: 24 patients were randomised in a double-blind,
      prospective, cross-over trial. At baseline and after 12 weeks of either treatment
      an oGTT, and endothelial function testing was performed. RESULTS: Endothelial
      function improved significantly by telmisartan treatment but not by losartan
      treatment (FMD; T: 7.9 +/- 0.7%, vs B: 6.4 +/- 0.8, p<0.01; vs L: 6.4 +/- 0.6,
      p<0.001) at almost identical antihypertensive effect of both agents. Insulin
      resistance assessed by HOMA (T: 2.20 +/- 0.47 vs B: 3.04 +/- 0.60, p<0.01; vs L:
      3.38 +/- 0.84, T vs L p<0.05) and ISI120 (T: 0.114 +/- 0.003 vs B: 0.092 +/-
      0.002, p<0.001; vs L: 0.090 +/- 0.006, T vs L p<0.01) improved significantly
      after telmisartan only, as did glucose tolerance (p<0.01). The improvement of the
      endothelial function observed, significantly depended on pretreatment insulin
      resistance but was independent of improvements of insulin resistance, blood
      pressure or glucose tolerance. CONCLUSION: In hypertensive patients with IGT
      telmisartan compared to losartan improved endothelial function and insulin
      resistance independently, supporting the hypothesis that glucometabolic and
      vascular insulin resistance are differentially regulated.

PMID- 19118912
TI  - Cost of medical care among type 2 diabetic patients with a co-morbid condition-
      hypertension in India.
AB  - The aim was to estimate the cost of medical care among hospitalized diabetic
      patients and to assess the influence of an additional co-morbid condition
      hypertension. A pre tested and validated questionnaire was interviewer
      administered among 443 (male:female, 235:208) hospitalized diabetic patients. The
      JNC VII criteria for hypertension was considered to divide the study population
      into two groups; group I - diabetic patients without hypertension (n=269) and
      group II - diabetic patients with hypertension (n=174). Details of cost of
      inpatient and out-patient care and expenditure on hospitalization for the
      previous 2 years were obtained. The prevalence of hypertension among the study
      subjects was 39.3% (174 subjects). Presence of hypertension made a significant
      impact on the expenditure pattern. On an average a diabetic patient with
      hypertension spent 1.4 times more than a diabetic subject without hypertension.
      Median cost per hospitalization, length of stay during admission, and cost of 2
      years for inpatient admission were all significantly higher for diabetic patients
      with a co-morbid condition. There is a need to develop a protocol on cost
      effective strategy for diabetes care. Strict control of hypertension should be
      targeted to avoid excess treatment cost on diabetes care.

PMID- 19118914
TI  - Usefulness of serum cystatin C in Japanese patients with type 2 diabetes mellitus
      and nephropathy.
AB  - We examined usefulness of serum cystatin C to detect chronic kidney disease (CKD)
      stage >or=3, which was defined by Modification of Diet in Renal Disease formula.
      Serum cystatin C could detect CKD stage >or=3 with high efficacy in 289 Japanese
      patients with type 2 diabetes and nephropathy.

PMID- 19118913
TI  - Vildagliptin dose-dependently improves glycemic control in Japanese patients with
      type 2 diabetes mellitus.
AB  - OBJECTIVE: To assess the efficacy and tolerability of vildagliptin (10, 25 or
      50mg bid) in Japanese patients with type 2 diabetes mellitus (T2DM). METHODS:
      This 12-week, multicenter, randomized, double-blind, placebo-controlled, parallel
      group study was performed in 291 patients. The primary assessment was change from
      baseline to endpoint in HbA1c. RESULTS: Baseline HbA1c averaged 7.4%, and the
      between-treatment difference (vildagliptin-placebo) in the HbA1c adjusted mean
      change was -0.8%, -1.0% and -1.2% with vildagliptin 10, 25 and 50mg bid,
      respectively (p<0.001). Relative to baseline, body weight did not change
      significantly in vildagliptin groups. There was no increase in incidence of
      adverse events in the vildagliptin groups (62.0%, 62.5% and 61.8%, 10, 25 and
      50mg bid, respectively) compared to placebo (73.6%). No deaths or drug-related
      serious adverse events were reported. Seven hypoglycemic events were observed
      (four events (n=3), two events (n=2), and one event (n=1) in the vildagliptin 10
      and 50mg bid, and placebo, respectively) and none of them were severe or dose
      related. CONCLUSION: Vildagliptin 50mg bid was considered to be the most
      effective and well-tolerated dose, and therefore can be considered the
      recommended clinical dose for Japanese patients with T2DM.

PMID- 19118915
TI  - Genotype-phenotype correlation in Italian children with Wilson's disease.
AB  - BACKGROUND/AIMS: Wilson's disease phenotype is very variable for clinical and
      laboratory features. Our aim was to assess the role of the type of ATP7B disease
      causing mutations on Wilson's disease phenotype. METHODS: We retrospectively
      evaluated the data of children with Wilson's disease from eight pediatric
      departments. RESULT: Fifty-eight patients (34 male, median age at diagnosis 7.4
      years) from 47 unrelated families were studied, carrying 34 different mutations.
      The most common mutations were the missense p.H1069Q and p.M769V, the nonsense
      p.R1319X, the frameshift c.2299delC, c.2298_2299insC and c.2530delA, and the
      splice site mutation c.2447+5G>A. Serum ceruloplasmin and copper were lower among
      the patients' homozygotes for nonsense and frameshift mutations than in patients
      with missense mutations. A normalization of serum alanine aminotransferase after
      therapy was not achieved in 23.6% of patients with missense mutations versus
      45.5% of patients with nonsense/frameshift mutations. A direct linear correlation
      was found between age at diagnosis and urinary copper excretion at diagnosis.
      CONCLUSIONS: The type of mutation explains at least a part of Wilson's disease
      phenotype, and mutation analysis should be considered as an integrative tool for
      such a challenging diagnosis. Urinary copper excretion appears to be correlated
      to the age at diagnosis rather than genotype.

PMID- 19118916
TI  - Role of genotyping in Wilson's disease.

PMID- 19118917
TI  - Challenges for performance assessment and improvement in primary health care: the
      case of the Portuguese health centres.
AB  - Primary care is currently at the heart of health service policy, both in Portugal
      and internationally. At the same time, interest in the measurement of efficiency
      of health care delivery has increased considerably. However, very few studies
      have focused specifically on performance assessment in primary health care
      provision. In this paper we aim to contribute to a discussion regarding
      appropriate ways to compare the performance of primary health care providers.
      Following a review of the literature, a conceptual framework for performance
      assessment of health centres is developed and tested using the Portuguese case.
      Our empirical analysis uses data from 2004 and 2005 for all the Portuguese health
      centres and compares the geographical equity of access to services, technical
      efficiency and quality of services across district health authorities. Data
      envelopment analysis is the technique used to measure technical efficiency. From
      our empirical analysis, we conclude that there is evidence of large variation in
      equity of access to services, in technical efficiency and quality of services
      across district health authorities. Our findings suggest that a better use of
      resources could lead to more and improved services. Whilst formative evaluation
      could contribute to this, the challenge is to engage health care professionals in
      the evaluation exercise.

PMID- 19118918
TI  - Commissioning NHS dentistry in England: issues for decision-makers managing the
      new contract with finite resources.
AB  - OBJECTIVES: To explore the views of dental decision-makers in Primary Care
      Organisations with regard to the management of NHS dental services, and to gauge
      participants' awareness of economics-based approaches including programme
      budgeting and marginal analysis, with which to potentially structure
      commissioning decisions. METHODS: Recorded semi-structured interviews were
      conducted with 18 NHS dental decision-makers (mixed clinical and finance
      backgrounds) predominantly across Primary Care Trusts in England. Data were
      analysed using qualitative methods and the constant comparative approach.
      RESULTS: Participants were generally involved with contracting rather than
      commissioning new dental services at the time of interview. It was unclear how
      oral health needs assessments would guide future resource shifts and how
      commissioners would ensure the efficient use of finite resources. Whilst many
      participants thought that economic approaches would assist their commissioning
      decisions, few participants were aware of programme budgeting and marginal
      analysis as an alternative economics-based approach. CONCLUSIONS: An assessment
      of the extent to which finite resources actually maximise the oral health of
      local populations is timely. Pragmatic economic approaches such as programme
      budgeting and marginal analysis may offer a framework to guide decision-makers
      through commissioning and the stages which lie beyond oral health needs
      assessments.

PMID- 19118919
TI  - Efficacy of intensified chemotherapy with hematopoietic progenitors in small-cell
      lung cancer: A meta-analysis of the published literature.
AB  - OBJECTIVE: It remains controversial whether intensified chemotherapy with
      hematopoietic progenitors (ICHP) is effective for small-cell lung cancer. This
      meta-analysis was performed to evaluate the efficacy and safety of ICHP in
      patients with small-cell lung cancer. METHODS: MEDLINE and EMBASE databases were
      searched for English-language studies published through October 12, 2008.
      Randomized phase II and III clinical trials comparing ICHP with control therapy.
      Response rates, overall survival, and toxicity were analyzed. RESULTS: Five
      assessable trials were identified including 641 patients. No significant increase
      in the odds ratio for response was attributable to ICHP (odds ratio, 1.29; 95%
      confidence interval, 0.87-1.93; p=0.206). No statistically significant increase
      in overall survival was found when ICHP were compared to control regimens (hazard
      ratio, 0.94; 95% confidence interval, 0.80-1.10; p=0.432). The toxicity of ICHP
      was significantly higher for hematologic toxicity, including hemoglobin nadir and
      platelet nadir. CONCLUSIONS: ICHP was not superior to control chemotherapy in
      terms of both objective response and overall survival, and was related to more
      significant hemoglobin nadir and platelet nadir.

PMID- 19118920
TI  - A comparison of the antibacterial efficacy and cytotoxicity to cultured human
      skin cells of 7 commercial hand rubs and Xgel, a new copper-based biocidal hand
      rub.
AB  - BACKGROUND: Hand cleanliness is important in hospital infection control, but skin
      irritation from frequent alcohol-based hand rub use reduces compliance. We have
      compared a new copper biocide/Aloe vera-based biocidal hand rub (Xgel) with 7
      commercially available hand rubs. METHODS: Hand rubs were cultured with human
      skin cells for 24 hours after which cytotoxicity was assessed using the
      sulforhodamine B assay. The EN 12054 bacterial suspension test protocol was used
      to assess biocidal activity of 2 of the least cytotoxic hand rubs (Xgel and
      Purell). RESULTS: Hand rubs had 50% cytotoxic concentrations ranging from >10% to
      <0.1% vol/vol. In the EN12054 assay, Xgel reduced colony forming units (CFU) by
      >10(8) with methicillin-resistant Staphylococcus aureus (MRSA) and Acinetobacter
      in 1 minute, whereas Purell only reduced CFU by 10(4) and 10(5), respectively.
      Purell was ineffective against C difficile spores, whereas Xgel produced a 3 x
      10(3) reduction in CFU. CONCLUSION: The hand rubs had a wide range of
      cytotoxicity values for human skin cells, with Xgel being the least cytotoxic to
      human skin cells. In the EN 12054 bacterial suspension test, Xgel was more
      effective than Purell against all organisms tested. It should be noted that these
      in vitro results may not translate into clinical differences.

PMID- 19118921
TI  - Measuring adherence to hand hygiene guidelines: a field survey for examples of
      effective practices.
AB  - BACKGROUND: Measuring adherence to hand hygiene guidelines is resource intensive
      and complicated by lack of standardized methodology. The multiplicity of
      approaches in use makes it difficult to meaningfully compare performance across
      health care organizations. The goal of this project was to identify promising and
      effective practices for measuring adherence with hand hygiene guidelines across a
      variety of settings. METHODS: A cross-sectional survey was conducted
      electronically in February 2007 to collect information on aspects of hand hygiene
      measured (eg, frequency, thoroughness of technique, glove use, product
      consumption), data collection approaches, training and resources, reports, and
      others. Invitations to respond were widely distributed through Web site
      announcements and list-serve messages of The Joint Commission and collaborating
      organizations. A panel of national experts developed and applied criteria for
      evaluating the methods. RESULTS: Two hundred forty-two responses were submitted
      from a variety of settings and countries. Most (approximately 75%) measured
      frequency of hand hygiene; approximately 50% measured thoroughness, glove use,
      product usage, patient and provider satisfaction, or other aspects. Seventy-two
      percent relied exclusively on manual data collection, and most methods (80%) had
      been in use for less than 3 years. Most (65%) spent less than 1 hour in training
      data collectors, and few had evidence of reliability or validity. Forty
      submissions met most criteria for inclusion in an educational monograph.
      CONCLUSION: Among respondents who considered their approach to be an example of
      an effective practice, there was substantial variation in methods and little
      evidence of reliability. Standardization of methods is needed to compare
      performance across organizations or within an organization over time.

PMID- 19118922
TI  - The changing susceptibilities of methicillin-resistant Staphylococcus aureus at a
      midwestern hospital: the emergence of "community-associated" MRSA.
AB  - BACKGROUND: The emergence of community-associated methicillin-resistant
      Staphylococcus aureus (CA-MRSA) has been well described; however, few studies
      have reviewed long-term hospital-wide data. METHODS: This retrospective study of
      adult patients used the first culture per patient per visit positive for MRSA for
      1996 to 2005. Isolates were categorized as community-associated or health care
      associated phenotype based on antibiotic susceptibilities. chi(2) tests for trend
      and linear regression analyses were performed. RESULTS: The annual prevalence of
      CA-MRSA increased significantly over the 10-year study period (from 43 of 507
      [8.9%] MRSA cultures in 1996 to 672 of 1697 [39.6%] MRSA cultures in 2005; P <
      .01). The proportion of MRSA cultures obtained within 48 hours of hospital
      admission increased from 50.5% to 79.5% (P < .01). The median age of patients
      with MRSA decreased, from 60 to 49 years (P < .01). Among the CA-MRSA cases, the
      proportion of non-Caucasian patients increased from 30.2% to 60.4% (P < .01) and
      the proportion of patients categorized as low socioeconomic status increased from
      25.6% to 35.6% (P < .01). Significant consistent trends were not observed for
      patient sex or body sites of the cultures. CONCLUSION: An increasing number of
      MRSA with a community-associated phenotype occurred during the 10-year study
      period. Patterns of decreasing age, increasing non-Caucasian races, and
      decreasing socioeconomic status were observed among patients with MRSA.

PMID- 19118923
TI  - The role of interventional molecular epidemiology in controlling clonal clusters
      of multidrug resistant Pseudomonas aeruginosa in critically ill cancer patients.
AB  - BACKGROUND: Pseudomonas aeruginosa is one of the leading causes of hospital
      acquired infections in intensive care units (ICUs). The objective was to evaluate
      the impact of molecular identification of clonal multidrug-resistant (MDR) P
      aeruginosa strains and the implementation of infection control measures. METHODS:
      One hundred seventy-seven strains from ICU patients infected or colonized with
      MDR P aeruginosa from May 2001 to April 2006 were collected. In vitro
      susceptibility to 16 antibiotics was done. Pulsed-field gel electrophoresis was
      performed to identify clonal strains. Nosocomial outbreak was defined as the
      presence of > or =3 MDR P aeruginosa over < or =3 consecutive months. RESULTS:
      During the 5 years of the study, 25 infected and 14 colonized patients with a
      clonal strain of MDR P aeruginosa were distributed among 5 episodic clusters.
      These strains were only susceptible to ceftazidime and colistin. Molecular
      biology identification, diligent monitoring, and multidisciplinary infection
      control interventions were implemented to suppress this clonal strain after each
      cluster. Even more, after the last outbreak (June-August 2005), the infection
      control measures were able to reduce the MDR P aeruginosa to zero during the last
      8 months of this study. CONCLUSION: Interventional molecular epidemiology
      combined with early identification, monitoring, and implementation of
      multidisciplinary infection control measures can control temporarily the
      transmission of MDR P aeruginosa infection in ICUs.

PMID- 19118925
TI  - QSAR model for predicting radical scavenging activity of di(hetero)arylamines
      derivatives of benzo[b]thiophenes.
AB  - A QSAR study was developed in order to model the antioxidant activity,
      specifically the radical scavenger activity (RSA), of 26 di(hetero)arylamines'
      derivatives of benzo[b]thiophenes. The QSAR model was constructed, using the
      partial least squares projection of latent structures (PLS) method, and its
      robustness and predictability were verified by internal and external cross
      validation methods. A total of 4 molecular descriptors, belonging to RDF (Radial
      Distribution Function) descriptors (RDF020e and RDF045e) and 2D-autocorrelation
      descriptors (GATS8p and MATS5e) were selected to build the QSAR model. RDF
      descriptors seem to relate the presence of electronegative atoms at the inner
      atmosphere of the compounds to increase RSA. 2D-Autocorrelation descriptors
      associate the presence of polarizable and electronegative pairs of atoms, at
      specific topological distance, with the RSA of the compounds. Finally this QSAR
      model proved to be a useful tool in the prediction of radical scavenger activity
      of congeneric compounds and will be used to guide the synthesis of new
      diarylamines in our laboratory.

PMID- 19118924
TI  - Age-associated changes in synaptic lipid raft proteins revealed by two
      dimensional fluorescence difference gel electrophoresis.
AB  - Brain aging is associated with a progressive decline in cognitive function though
      the molecular mechanisms remain unknown. Functional changes in brain neurons
      could be due to age-related alterations in levels of specific proteins critical
      for information processing. Specialized membrane microdomains known as 'lipid
      rafts' contain protein complexes involved in many signal transduction processes.
      This study was undertaken to determine if two-dimensional fluorescence difference
      gel electrophoresis (2D DIGE) analysis of proteins in synaptic membrane lipid
      rafts revealed age-dependent alterations in levels of raft proteins. Five pairs
      of young and aged rat synaptic membrane rafts were subjected to DIGE separation,
      followed by image analysis and identification of significantly altered proteins.
      Of 1046 matched spots on DIGE gels, 94 showed statistically significant
      differences in levels between old and young rafts, and 87 of these were decreased
      in aged rafts. The 41 most significantly altered (p<0.03) proteins included
      several synaptic proteins involved in energy metabolism, redox homeostasis, and
      cytoskeletal structure. This may indicate a disruption in bioenergetic balance
      and redox homeostasis in synaptic rafts with brain aging. Differential levels of
      representative identified proteins were confirmed by immunoblot analysis. Our
      findings provide novel pathways in investigations of mechanisms that may
      contribute to altered neuronal function in aging brain.

PMID- 19118926
TI  - [Gleich's syndrome: a case report].
AB  - The Gleich's syndrome is a rare disease that causes recurrent angioedema
      associated with major eosinophilia with good response to corticosteroids. We
      describe a 53-year-old man who presented with a Gleich's syndrome with a 6-year
      follow-up and propose a literature review. This case emphazises the favourable
      prognosis of this disease. In case of poor tolerance of corticosteroids,
      mepolizumab could be tested.

PMID- 19118927
TI  - The subject of pedagogy from theory to practice--the view of newly registered
      nurses.
AB  - The aim was to describe, from the newly registered nurses' perspective, specific
      events when using their pedagogical knowledge in their everyday clinical
      practice. The design was qualitative and the critical incident technique was
      used. Data was collected via interviews with ten newly registered nurses who
      graduated from the same University program 10 months earlier and are now employed
      at a university hospital. Two categories emerged in the analyses. The first
      category was "Pedagogical methods in theory" with the sub-categories Theory and
      the application of the course in practice, Knowledge of pedagogy and Information
      as a professional competence. The second category was "Pedagogical methods in
      everyday clinical practice" with sub-categories Factual knowledge versus
      pedagogical knowledge, Information and relatives, Difficulties when giving
      information, Understanding information received, Pedagogical tools, Collaboration
      in teams in pedagogical situations, and Time and giving information. By
      identifying specific events regarding pedagogical methods the findings can be
      useful for everyone from teachers and health-care managers to nurse students and
      newly registered nurses, to improve teaching methods in nurse education.

PMID- 19118928
TI  - Job satisfaction of nurse teachers: a literature review. Part II: Effects and
      related factors.
AB  - This paper reports the effects and related factors of nurse teachers' job
      satisfaction. Much of the research to date has focused on the factors of job
      satisfaction with recent studies providing some evidence about its predictors.
      However, little research has focused on the effects of job satisfaction on
      individual nurse teachers or from an organizational or student perspective
      despite the growing global shortage of nurse teachers. The challenge and
      potential direction of research are discussed and it is argued that there is a
      need to establish a comprehensive model of job satisfaction and measure the
      impact of nurse teachers' job satisfaction from the perspective of key
      stakeholders.

PMID- 19118929
TI  - Panendoscopy and simultaneous primary tumours in patients presenting with early
      carcinoma of the mobile tongue.
AB  - Many patients who present with primary malignant disease of the head and neck are
      examined under anaesthesia to see if they have synchronous tumours. Although
      previous studies have attempted to establish whether this is either efficient or
      cost-effective, the patients included tended to include heterogeneous index sites
      as well as newly-diagnosed and previously-diagnosed tumours. Seventy-four
      patients who presented with newly-diagnosed early carcinoma of the mobile tongue
      (T1 N0 / T2 N0) were studied. None had any symptoms of other upper aerodigestive
      tract disease and all had panendoscopy including bronchoscopy and oesophagoscopy.
      Only three had serious abnormalities, of which two were synchronous carcinomas.
      In no patient did the findings of the panendoscopy influence definitive treatment
      of the index tumour.Although there was no morbidity associated with panendoscopy
      among these patients, the routine use of panendoscopy we conclude that it is not
      warranted.

PMID- 19118930
TI  - Fixed and mobile bearing total knee arthroplasty--influence on wear generation,
      corresponding wear areas, knee kinematics and particle composition.
AB  - BACKGROUND: Several studies in literature are dealing with a direct comparison
      between fixed and mobile bearing knee replacements, but to our knowledge there is
      no published data comparing the wear behaviour of the two design principles based
      on the same femur and superior gliding surface geometry. The objective of our
      study was to investigate a fixed and mobile bearing knee design with identical
      femoral articulation in regard to wear, tibio-femoral kinematics and particle
      size distribution. METHODS: In vitro wear simulation according to ISO 14243-1 has
      been performed with the Columbus knee system (Aesculap, Tuttlingen) in the
      configurations fixed and mobile bearing for five million cycles on a customized
      four station knee wear simulator. The tests were running under force control and
      the tibio-femoral kinematics were assessed. A particle analysis has been
      undergone after each inspection interval when the lubricant was replaced.
      FINDINGS: Due to the additional wear in the tibial articulation of the mobile
      bearing design the mean gravimetric wear rates are not statistically different
      between the two groups. Apart of that there is a substantial reduction in the
      amount of wear per area unit for the mobile versus the fixed bearing gliding
      surfaces. Both groups show comparable tibio-femoral kinematics and a similar wear
      debris morphology. INTERPRETATION: Our investigation of a fixed and mobile
      bearing knee design with identical femoral articulation demonstrates that there
      are no significant differences in wear rate, resulting kinematics and
      polyethylene particle release. Therefore it can be recommended that surgeons
      decision for one or the other design principle should be based on the individual
      patient profile.

PMID- 19118931
TI  - Comparison of concentrations of mercury in ambient air to its accumulation by
      leafy vegetables: an important step in terrestrial food chain analysis.
AB  - A biomonitoring network with leafy vegetables was established near a chlor-alkali
      plant in order to compare the accumulation of mercury to the atmospheric total
      gaseous mercury (TGM) concentration. Based on data obtained in the reference area
      the 'normal' mercury concentration in vegetables is between 0.6 and 5.4 microg
      kg(-1) FW. The effect detection limits (EDLs) are between 1.2 and 11.0 microg kg(
      1) FW and the biological detection limits (BDLs), the lowest [TGM] that can be
      detected significantly, are between 3 and 4 ng m(-3). The accumulation rate is
      lowest for lettuce and high for curly kale that proved to be an excellent
      accumulator and as such it is very useful for biomonitoring purposes. A
      comparison made in the 1980s between biomonitoring results with grass and the
      mercury concentration in leafy vegetables from private gardens nearby proved to
      be valid when applied to the current biomonitoring results with vegetables.

PMID- 19118932
TI  - Source identification of copper, lead, nickel, and zinc loading in wastewater
      reclamation plant influents from corrosion of brass in plumbing fixtures.
AB  - A natural experiment indicated that a link between the presence and concentration
      of four elements, copper, lead, nickel, and zinc in the influent to two
      wastewater reclamation plants to the presence and concentrations of the same four
      elements in the tap water of residential properties. There were 36 populations of
      results that were assessed for the normality of their distribution, the
      difference in their median concentrations, the similarity in the ratios of their
      median concentrations, and the correlations of the concentrations. The results of
      this study suggest that brass corrosion is the major source of these four
      elements in the water reclamation plants influent and that there are two distinct
      populations of brass sources, those in the early stages of dezincification where
      the release of the non-copper elements is dominant and those in the later stages
      where the release of copper dominates and the type of brass that is corroding.

PMID- 19118933
TI  - Arsenic stability and mobilization in soil at an amenity grassland overlying
      chemical waste (St. Helens, UK).
AB  - A 6.6 ha grassland, established on a former chemical waste site adjacent to a
      residential area, contains arsenic (As) in surface soil at concentrations 200
      times higher than UK Soil Guideline Values. The site is not recognized as
      statutory contaminated land, partly on the assumption that mobility of the
      metalloid presents a negligible threat to human health, groundwater and
      ecological receptors. Evidence for this is evaluated, based on studies of the
      effect of organic (green waste compost) and inorganic (iron oxides, lime and
      phosphate) amendments on As fractionation, mobility, plant uptake and earthworm
      communities. Arsenic mobility in soil was low but significantly related to
      dissolved organic matter and phosphate, with immobilization associated with iron
      oxides. Plant uptake was low and there was little apparent impact on earthworms.
      The existing vegetation cover reduces re-entrainment of dust-blown particulates
      and pathways of As exposure via this route. Minimizing risks to receptors
      requires avoidance of soil exposure, and no compost or phosphate application.

PMID- 19118934
TI  - Is population mixing associated with childhood type 1 diabetes in Canterbury, New
      Zealand?
AB  - There is growing evidence to support a role for infections in the aetiology of
      childhood type 1 diabetes. However, previous studies suggest that infections can
      either protect against or initiate type 1 diabetes onset, depending on the timing
      of exposure. Population mixing has recently been employed as a proxy measure for
      area-level infectious exposure in childhood diabetes research. Research has found
      that the incidence of type 1 diabetes tends to be higher in areas with low
      population mixing, suggesting that children with low infectious exposure in early
      life have increased susceptibility to the disease. Subsequent exposure to
      infection could act as the final trigger to type 1 diabetes development. We
      assess whether an increase in population mixing over a short time period is
      associated with a higher incidence of type 1 diabetes. We test this hypothesis
      using data on childhood type 1 diabetes from the Canterbury region in New Zealand
      for the period 1999-2004, and population mixing change measures derived from the
      1996 and 2001 censuses. We found that the incidence of type 1 diabetes was higher
      in areas where population mixing had increased the most. This effect was small,
      but remained significant after adjustment for potential confounding variables.
      The findings suggest that large increases in population mixing, over short time
      periods, could act as a trigger for type 1 diabetes development in children.

PMID- 19118935
TI  - Anaphylaxis-Junior doctors' knowledge of guidelines.

PMID- 19118936
TI  - Reducing the costs of meeting regional water demand through risk-based transfer
      agreements.
AB  - Transfers of treated water among inter-connected utilities is becoming more
      common as the cost of developing new supplies grows, and transfer agreements
      require well developed rules describing when and how much water will be
      transferred. The nature of the decision rules governing an agreement must also be
      coordinated with respect to the treatment and conveyance capacity required to
      execute the transfers. This study explores different combinations of
      infrastructure and agreement type that define three different transfer programs,
      describing the frequency and volume of transfers associated with each, as well as
      their costs. The agreements are described in terms of the type of decision rule
      employed: Take-or-Pay, where the timing and quantity of transfers is fixed; Days
      of Supply Remaining (DSR), which uses a static hydrologic indicator to trigger
      transfers; and Risk-of-Failure, a probability-based decision rule that involves
      consideration of both supply and demand. This analysis is conducted within the
      context of the Research Triangle area of North Carolina (USA), a rapidly growing
      area that is beginning to approach the practical limits of water resource
      development. The Risk-of-Failure agreement is shown to reduce the average volume
      of transfers by over 80% compared to a Take-or-Pay agreement and by roughly half
      relative to the DSR agreement, leading to significant cost reductions. A
      utility's willingness to accept something less than guaranteed access to a
      specified quantity of water (i.e. an interruption) also has a significant impact
      on cost. Interruptions do not necessarily lead to lower reliability, but rather
      to the purchasing utility acquiring more water during off-peak periods when the
      seller has excess treatment capacity available. The lowest cost guaranteed
      agreement is 40-50% more expensive than the lowest cost interruptible contract.

PMID- 19118937
TI  - An innovative modeling approach using Qual2K and HEC-RAS integration to assess
      the impact of tidal effect on River Water quality simulation.
AB  - Water quality modeling has been shown to be a useful tool in strategic water
      quality management. The present study combines the Qual2K model with the HEC-RAS
      model to assess the water quality of a tidal river in northern Taiwan. The
      contaminant loadings of biochemical oxygen demand (BOD), ammonia nitrogen (NH(3)
      N), total phosphorus (TP), and sediment oxygen demand (SOD) are utilized in the
      Qual2K simulation. The HEC-RAS model is used to: (i) estimate the hydraulic
      constants for atmospheric re-aeration constant calculation; and (ii) calculate
      the water level profile variation to account for concentration changes as a
      result of tidal effect. The results show that HEC-RAS-assisted Qual2K simulations
      taking tidal effect into consideration produce water quality indices that, in
      general, agree with the monitoring data of the river. Comparisons of simulations
      with different combinations of contaminant loadings demonstrate that BOD is the
      most import contaminant. Streeter-Phelps simulation (in combination with HEC-RAS)
      is also performed for comparison, and the results show excellent agreement with
      the observed data. This paper is the first report of the innovative use of a
      combination of the HEC-RAS model and the Qual2K model (or Streeter-Phelps
      equation) to simulate water quality in a tidal river. The combination is shown to
      provide an alternative for water quality simulation of a tidal river when
      available dynamic-monitoring data are insufficient to assess the tidal effect of
      the river.

PMID- 19118938
TI  - Monitoring of cell death in epithelial cells using high frequency ultrasound
      spectroscopy.
AB  - Spectral and wavelet analyses were performed on ultrasound radiofrequency (RF)
      data collected from centrifuged cell samples containing HEp-2 cells after
      induction of apoptosis by exposure to camptothecin. Samples were imaged at
      several time points after drug exposure using high-frequency ultrasound in the
      range from 10-60 MHz. A 20-MHz transducer with a f-number of 2.35 and a 40-MHz
      transducer with a f-number of 3 were used for collecting the RF data. Normalized
      power spectra were computed from the backscattered ultrasound signals within a
      region-of-interest (ROI) for further analysis. Spectral slopes, integrated
      backscatter coefficients (IBCs) and wavelet parameters were estimated as a
      function of treatment time to monitor acoustic property changes during apoptosis.
      Changes in spectral parameters were detected starting six hours after treatment
      and coincided with changes in corresponding histology. Throughout the course of
      chemotherapy, variation in estimates of the spectral slope of up to 35% were
      observed. During the treatment, IBCs increased by 400% compared with estimates
      obtained from the control samples. Changes in spectral parameters are
      hypothesized to be linked to structural cell changes during apoptosis. In
      addition, the sensitivity of a wavelet-based analysis to the ultrasonic
      assessment of cellular changes was investigated. Results of the wavelet analysis
      showed variations similar to the spectral parameters. Where values of the
      spectral slope decreased, estimates of the scaling factors increased. Because
      wavelet analysis preserves the signal-time localization, its application will be
      potentially beneficial for assessing treatment responses in vivo. The current
      study contributes toward the development of a non-invasive method for monitoring
      apoptosis as a measure of the success of chemotherapeutic treatment of cancer.

PMID- 19118939
TI  - Evidence of mitochondrial damage in the levator ani muscle of women with pelvic
      organ prolapse.

PMID- 19118940
TI  - Bilateral ballism induced by gabapentin in idiopatic Parkinson's disease.

PMID- 19118941
TI  - Neuromedin U is overexpressed in pancreatic cancer and increases invasiveness via
      the hepatocyte growth factor c-Met pathway.
AB  - Neuromedin U (NmU) is a bioactive peptide, ubiquitously expressed in the
      gastrointestinal tract. Here, we analyzed the role of NmU in pancreatic ductal
      adenocarcinoma (PDAC) pathogenesis. NmU and NmU receptor-2 mRNA were
      significantly overexpressed in PDAC and in metastatic tissues. NmU and NmU
      receptor-2 were localized predominantly in cancer cells. NmU serum levels
      decreased after tumor resection. Although NmU exerted no effects on cancer cell
      proliferation, it induced c-Met and a trend towards increased invasiveness as
      well as an increased hepatocyte growth factor (HGF)-mediated scattering. Thus,
      NmU may be involved in the HGF-c-Met paracrine loop regulating cell migration,
      invasiveness and dissemination of PDAC.

PMID- 19118942
TI  - Strain-dependent differences in susceptibility to lung cancer in inbred mice
      exposed to mainstream cigarette smoke.
AB  - It is becoming increasingly clear that genetic susceptibility is an important
      host factor determining the effects of exposure to a number of airborne particles
      and gases. Although numerous studies have identified a genetic component for
      spontaneous pulmonary tumor development and for chemically induced lung cancer
      (e.g., urethane) in mice, a systematic examination of murine inter-strain
      differences in response to cigarette smoke inhalation has not been conducted. We
      addressed this research gap by examining the strain distribution pattern of lung
      cancer in nine inbred strains of mice exposed to 258 mg/m(3) mainstream cigarette
      smoke for 5 months followed by 4 months of rest. Lung tumors were enumerated on
      fixed lungs visualized at low magnification and on serial step sections examined
      microscopically. With the low magnification examination, we observed
      statistically significant increases in the number of lung tumors in cigarette
      smoke-exposed A/J and the genetically-related A/HeJ mice (p<0.05). While fewer
      tumors were identified by the microscopic enumeration method, it confirmed that
      significant increases in lung tumors occurred only in A/J and A/HeJ mice exposed
      to cigarette smoke (p<0.05). Thus, as predicted by epidemiologic studies and
      animal experiments using chemically induced lung cancer models, these findings
      suggest that genetic host factors play a significant role in the pulmonary
      tumorigenic response of mice to mainstream cigarette smoke.

PMID- 19118943
TI  - Coal fly ash-slag-based geopolymers: microstructure and metal leaching.
AB  - This study deals with the use of fly ash as a starting material for geopolymeric
      matrices. The leachable concentrations of geopolymers were compared with those of
      the starting fly ash to evaluate the retention of potentially harmful elements
      within the geopolymer matrix. Geopolymer matrices give rise to a leaching
      scenario characterised by a highly alkaline environment, which inhibits the
      leaching of heavy metals but may enhance the mobilization of certain oxyanionic
      species. Thus, fly ash-based geopolymers were found to immobilize a number of
      trace pollutants such as Be, Bi, Cd, Co, Cr, Cu, Nb, Ni, Pb, Sn, Th, U, Y, Zr and
      rare earth elements. However, the leachable levels of elements occurring in their
      oxyanionic form such as As, B, Mo, Se, V and W were increased after
      geopolymerization. This suggests that an optimal dosage, synthesis and curing
      conditions are essential in order to obtain a long-term stable final product that
      ensures an efficient physical encapsulation.

PMID- 19118944
TI  - Ozonation of tannery effluent for removal of cod and color.
AB  - Ozonation of leather dye effluent for removal of color and COD reduction covering
      wide range in operating parameters forms the scope of the present work. The
      influence of parameters such as influent pH, ozone flow rate and initial effluent
      concentration on ozonation efficiency has been critically examined. It has been
      observed from the present investigation that a maximum of COD removal efficiency
      of 92% has been achieved under optimum operating conditions. Further the
      biodegradability index of the tannery effluent has increased from an initial
      value of 0.18 to 0.49 during ozonation indicating favorable adaptation of
      ozonation as a primer to the biochemical technique to enhance the efficiency of
      biochemical treatment.

PMID- 19118945
TI  - A new hybrid ion exchanger: effect of system parameters on the adsorption of
      vanadium (V).
AB  - The hybrid ion exchanger consisted of PONF-g-GMA anion fibrous exchanger and IRA
      96 bead-type anion exchanger was developed by combining different types of layers
      with hot-melt adhesive. Its ion exchange capacity and the pressure drop with flow
      rate of water were measured and the adsorption of vanadium (V) ions on the hybrid
      ion exchanger was evaluated with various process parameters such as pH, initial
      concentration, and temperature. It was observed that the adsorption kinetics of
      vanadium (V) ions on the hybrid ion exchanger could be analyzed with pseudo
      second-order model.

PMID- 19118946
TI  - Chemical and ecotoxicological characterization of solid residues produced during
      the co-pyrolysis of plastics and pine biomass.
AB  - A mixture of 70% (w/w) pine biomass and 30% (w/w) plastics (mixture of
      polypropylene, polyethylene, and polystyrene) was subjected to pyrolysis at 400
      degrees C, for 15 min, with an initial pressure of 40 MPa. Part of the solid
      residue produced was subjected to extraction with dichloromethane (DCM). The
      extracted residue (residue A) and raw residue (residue B) were analyzed by weight
      loss combustion and submitted to the leaching test ISO/TS 21268-2 using two
      different leachants: DCM (0.2%, v/v) and calcium chloride (0.001 mol/L). The
      concentrations of the heavy metals Cd, Cr, Ni, Zn, Pb and Cu were determined in
      the eluates and in the two residues. The eluates were further characterized by
      determining their pH and the concentrations of benzene, toluene, ethylbenzene and
      xylenes (BTEX). The presence of other organic contaminants in the eluates was
      qualitatively evaluated by gas chromatography, coupled with mass spectrometry. An
      ecotoxicological characterization was also performed by using the bio-indicator
      Vibrio fischeri. The chemical and ecotoxicological results were analyzed
      according to the French proposal of Criteria on the Evaluation Methods of Waste
      Ecotoxicity (CEMWE). Residue A was not considered to be ecotoxic by the
      ecotoxicological criterion (EC(50) (30 min) >or=10%), but it was considered to be
      ecotoxic by the chemical criterion (Ni>or=0.5mg/L). Residue B was considered to
      be ecotoxic by the ecotoxicological criterion: EC(50) (30 min)<or=10%. Besides
      that, residue B was considered to be hazardous according the European legislation
      (BTEX concentrations higher than 100 ppb). The results indicate that volatile
      organic contaminants can be present in sufficient amounts in these residues and
      their eluates to induce ecotoxicity levels. The extraction of the pyrolysis
      residue with DCM was an efficient method for removing lighter organic
      contaminants.

PMID- 19118947
TI  - Ablation mechanism of polymer layered silicate nanocomposite heat shield.
AB  - Recent advances in polymer layered silicate nanocomposites especially improve
      flammability resistance; encourage the examination of this unique class of
      evolving materials as potential ablatives. Polymer layered silicate
      nanocomposites show excellent potential as ablative heat shields. Determining the
      thermal diffusivity together with the mass and energy transfer is an important
      problem encountered in design of heat shield system which pyrolyses and ablates
      at high temperature. The aim of this work is to give information on the influence
      of the experimental conditions to the estimated effective thermal diffusivity of
      ablative nanocomposite and composite materials. Here, we present the inverse
      solution to estimate the parameter used to identify the effective thermal
      diffusivity of resol type phenolic resin-asbestos cloth montmorillonite layered
      silicate nanocomposite and its composite counterpart. The experimental setup
      consists of a standard oxyacetylene flame test. The transient temperature
      measurements, taken from the top surface and through the thickness of the
      samples, are used in the inverse analysis to estimate the change of the effective
      thermal diffusivity. The results of this work clarify the mechanism of the
      ablation and thermal diffusivity of the layered silicate nanocomposite heat
      shields due to the high temperature degradation in comparison with its composite
      counterpart.

PMID- 19118948
TI  - Adsorption studies of methylene blue and phenol onto vetiver roots activated
      carbon prepared by chemical activation.
AB  - Vetiver roots have been utilized for the preparation of activated carbon (AC) by
      chemical activation with different impregnation ratios of phosphoric acid, X(P)
      (gH(3)PO(4)/g precursor): 0.5:1; 1:1 and 1.5:1. Textural characterization,
      determined by nitrogen adsorption at 77K shows that mixed microporous and
      mesoporous structures activated carbons (ACs) with high surface area (>1000
      m(2)/g) and high pore volume (up to 1.19 cm(3)/g) can be obtained. The surface
      chemical properties of these ACs were investigated by X-ray photoelectron
      spectroscopy (XPS) and Boehm titration. Their textural and chemical
      characteristics were compared to those of an AC sample obtained by steam
      activation of vetiver roots. Classical molecules used for characterizing liquid
      phase adsorption, phenol and methylene blue (MB), were used. Adsorption kinetics
      of MB and phenol have been studied using commonly used kinetic models, i.e., the
      pseudo-first-order model, the pseudo-second-order model, the intraparticle
      diffusion model and as well the fractal, BWS (Brouers, Weron and Sotolongo)
      kinetic equation. The correlation coefficients (R(2)) and the normalized standard
      deviation Deltaq (%) were determined showing globally, that the recently derived
      fractal kinetic equation could best describe the adsorption kinetics for the
      adsorbates tested here, indicating a complex adsorption mechanism. The
      experimental adsorption isotherms of these molecules on the activated carbon were
      as well analysed using four isotherms: the classical Freundlich, Langmuir,
      Redlich-Peterson equations, but as well the newly published deformed Weibull
      Brouers-Sotolongo isotherm. The results obtained from the application of the
      equations show that the best fits were achieved with the Brouers-Sotolongo
      equation and with the Redlich-Peterson equation. Influence of surface functional
      groups towards MB adsorption is as well studied using various ACs prepared from
      vetiver roots and sugar cane bagasse. Opposite effects governing MB and phenol
      adsorption mechanism on ACs are demonstrated. The various effects involved in
      adsorption mechanisms of each molecule are demonstrated.

PMID- 19118949
TI  - Evaluation of phosphate fertilizers for the stabilization of cadmium in highly
      contaminated soils.
AB  - The efficiency of three phosphate fertilizers including triple superphosphate
      (TSP), diammonium phosphate (DAP), and phosphate rock (PR) as stabilizing agents
      of cadmium-contaminated soils has been assessed in this study. Two types of
      assessment criteria, (a) the reduction of leachable cadmium concentration; and
      (b) the changes in Cd association with specific operational soil fraction based
      on the sequential extraction data, are used in the evaluation of stabilization
      performance of each fertilizer. Results of the study showed that after the 60-day
      stabilization, the leachable concentrations of Cd in PR-, DAP- and TSP- treated
      soils reduced from 306 mg/kg (the control) to 140, 34, and 12 mg/kg with the
      stabilization efficiency as TSP>DAP>PR. Results from the assessment of Cd
      speciation via sequential extraction procedure revealed that the soluble
      exchangeable fraction and the surface adsorption fraction of Cd in the soils
      treated with PO(4) fertilizers, especially with TSP, have been reduced
      considerably. In addition, it is found that the reduction was correspondingly
      related with the increase of more stable forms of cadmium: the metal bound to
      manganese oxides and the metal bound to crystalline iron oxides. Treatment
      efficiency increased as the phosphate dose (based on the molar ratio of PO(4)/Cd)
      increased. In addition, it was observed that stabilization was most effective
      when using the molar ratio of PO(4)/Cd at 2:1 and at least 21-day and 28-day
      stabilization time for TSP and DAP, respectively.

PMID- 19118950
TI  - 5-HT7 receptor activation inhibits mechanical hypersensitivity secondary to
      capsaicin sensitization in mice.
AB  - This work aimed to evaluate the potential role of the 5-HT(7) receptor in
      nociception secondary to a sensitizing stimulus in mice. For this purpose, the
      effects of relevant ligands (5-HT(7) receptor agonists: AS-19, MSD-5a, E-55888; 5
      HT(7) receptor antagonists: SB-258719, SB-269970; 5-HT(1A) receptor agonist: F
      13640; 5-HT(1A) receptor antagonist: WAY-100635) were assessed on capsaicin
      induced mechanical hypersensitivity, a pain behavior involving hypersensitivity
      of dorsal horn neurons (central sensitization). For the 5-HT(7) receptor agonists
      used, binding profile and intrinsic efficacy to stimulate cAMP formation in HEK
      293F cells expressing the human 5-HT(7) receptor were also evaluated. AS-19 and E
      55888 were selective for 5-HT(7) receptors. E-55888 was a full agonist whereas AS
      19 and MSD-5a behaved as partial agonists, with maximal effects corresponding to
      77% and 61%, respectively, of the cAMP response evoked by the full agonist 5-HT.
      Our in vivo results revealed that systemic administration of 5-HT(7) receptor
      agonists exerted a clear-cut dose-dependent antinociceptive effect that was
      prevented by 5-HT(7) receptor antagonists, but not by the 5-HT(1A) receptor
      antagonist. The order of efficacy (E-55888>AS-19>MSD-5a) matched their in vitro
      efficacy as 5-HT(7) receptor agonists. Contrary to agonists, a dose-dependent
      promotion of mechanical hypersensitivity was observed after administration of 5
      HT(7) receptor antagonists, substantiating the involvement of the 5-HT(7)
      receptor in the control of capsaicin-induced mechanical hypersensitivity. These
      findings suggest that serotonin exerts an inhibitory role in the control of
      nociception through activation of 5-HT(7) receptors, and point to a new potential
      therapeutic use of 5-HT(7) receptor agonists in the field of analgesia.

PMID- 19118951
TI  - Reciprocal space representations of helical objects and their projection images
      for helices constructed from motifs without spherical symmetry.
AB  - Formulas for predicting the 3-D reciprocal space cube and 2-D reciprocal space
      images that are slices of the cube (corresponding to real space images that are
      projections of the real space cube) are derived for the case when the motif of a
      helical object is not spherically symmetric. These formulas generalize much-used
      formulas due to Cochran et al. [The structure of synthetic polypeptides. I. The
      transform of atoms on a helix, Acta Crystallogr. 5 (1952) 581-586], for the case
      of a spherically symmetric motif. The new formulas allow control of the spatial
      resolution of the motif ranging from low-resolution spherically symmetric motifs
      as in Cochran et al. through moderate-resolution nonsymmetrical motifs to atomic
      resolution nonsymmetrical motifs which can also be treated by the methods of
      Cochran et al. as a superposition of spherically symmetric atomic motifs. The
      ability to control resolution may be useful in reconstruction algorithms
      analogous to phase extension algorithms in X-ray crystallography.

PMID- 19118952
TI  - Quantitative EFTEM mapping of near physiological calcium concentrations in
      biological specimens.
AB  - Although electron energy-loss spectroscopy (EELS) in the scanning transmission
      electron microscope (STEM) provides high sensitivity for measuring the important
      element, calcium, in biological specimens, the technique has been difficult to
      apply routinely, because of long acquisition times required. Here we describe a
      refinement of the complementary analytical technique of energy-filtered
      transmission electron microscopy (EFTEM), which enables rapid imaging of large
      cellular regions and measurement of calcium concentrations approaching
      physiological levels. Extraction of precise quantitative information is possible
      by averaging large numbers of pixels that are contained in organelles of
      interest. We employ a modified two-window approach in which the behavior of the
      background signal in the EELS spectrum can be modeled as a function of specimen
      thickness t expressed in terms of the inelastic mean free path lambda. By
      acquiring pairs of images, one above and one below the Ca L(2,3) edge, together
      with zero-loss and unfiltered images, which are used to determine a relative
      thickness (t/lambda) map, it is possible to correct the Ca L(2,3) signal for
      plural scattering. We have evaluated the detection limits of this technique by
      considering several sources of systematic errors and applied this method to
      determine mitochondrial total calcium concentrations in freeze-dried cryosections
      of rapidly frozen stimulated neurons. By analyzing 0.1 microm2 areas of specimen
      regions that do not contain calcium, it was found that the standard deviation in
      the measurement of Ca concentrations was about 20 mmol/kg dry weight,
      corresponding to a Ca:C atomic fraction of approximately 2 x 10(-4). Calcium
      concentrations in peripheral mitochondria of recently depolarized, and therefore
      stimulated and Ca loaded, frog sympathetic neurons were in reasonable agreement
      with previous data.

PMID- 19118953
TI  - Pulmonary vein electric shunting for therapy of atrial fibrillation.

PMID- 19118954
TI  - Within-subject comparison of the psychopharmacological profiles of oral
      hydrocodone and oxycodone combination products in non-drug-abusing volunteers.
AB  - BACKGROUND: Non-medical use and abuse of prescription opioids is a significant
      problem in the United States. Little attention has been paid to assessing the
      relative psychopharmacological profile (including abuse liability-related
      effects) of specific prescription opioids. The purpose of this study was to
      directly compare the psychopharmacological profile of two widely prescribed and
      abused oral opioid combination products within the same subject. METHODS: Twenty
      non-drug-abusing volunteers participated in a crossover, randomized, double-blind
      study in which they received, all p.o.: placebo; 975 mg acetaminophen (ACET);
      10mg oxycodone (OXY)/487 mg ACET; 20mg OXY/975 mg ACET; 15 mg hydrocodone
      (HYD)/487 mg ACET; and 30mg HYD/975 mg ACET. OXY and HYD doses were chosen to
      equate the drugs on an objective measure of opiate effects: miosis. Dependent
      measures were subjective, psychomotor/cognitive, reinforcing, and physiological
      effects, and relative potency estimates. RESULTS: In general, the two opioid
      combination products at equi-miotic doses produced similar prototypic opiate-like
      effects and psychomotor impairment, and of similar magnitude. The higher dose of
      OXY/ACET produced slightly more abuse liability-related subjective effects than
      the higher dose of HYD/OXY, but also produced slightly more negative effects.
      Neither drug at either dose functioned as a reinforcer, as measured by the
      Multiple Choice Procedure. Relative potency ratios indicated that OXY/ACET was
      approximately 1.5 times more potent than HYD/ACET. CONCLUSIONS: Consistent with a
      recent study published in this journal using identical doses of HYD and OXY
      (without ACET) in prescription opioid abusers (Walsh, S.L., Nuzzo, P.A., Lofwall,
      M.R., Holtman Jr., J.R., 2008. The relative abuse liability of oral oxycodone,
      hydrocodone and hydromorphone assessed in prescription drug abusers. Drug Alcohol
      Depend. 198, 191-202), we found little difference in the pharmacodynamic effects
      of HYD/ACET and OXY/ACET in non-drug-abusing volunteers.

PMID- 19118955
TI  - Evaluation of l-glutamine for cryopreservation of boar spermatozoa.
AB  - The aim of the present study was to evaluate the protective effect of L-glutamine
      (L-Gln) against cryopreservation injuries on boar sperm. In Experiment 1, L-Gln
      from 20 to 80 mM was evaluated as a supplement for a standard freezing extender
      (egg yolk - EY - 20%, and glycerol 3%). No significant improvement (P>0.05) was
      obtained for any post-thaw sperm parameter assessed (objective sperm motility -
      CASA system - and flow cytometric analysis of plasma and acrosomal membrane
      integrity -SYBR14/PI/PE-PNA- and plasma membrane stability -M540/YoPro1-). In
      Experiment 2, L-Gln was evaluated as a partial glycerol substitute in the
      freezing extender. Significant (P<0.05) enhancement of post-thaw sperm motion
      parameters was achieved in sperm frozen in the presence of 2% glycerol and 80 mM
      L-Gln compared to control (3% glycerol). In Experiment 3, L-Gln was evaluated as
      an EY substitute in the freezing extender, and no functional sperm were recovered
      after thawing sperm frozen in the presence of L-Gln and the absence of EY. In
      conclusion, L-Gln has the ability to cryoprotect boar sperm when it is used as a
      partial glycerol substitute in the freezing extender.

PMID- 19118956
TI  - Changes in body composition following a dietary and lifestyle intervention trial:
      the postmenopausal health study.
AB  - OBJECTIVE: To examine whether dietary changes and the consumption of dairy
      products fortified with calcium and vitamin D3 versus the use of a calcium
      supplement alone could have any effect on anthropometric and body composition
      indices of postmenopausal women over a 12-month period. METHODS: 101 healthy
      postmenopausal women were randomized to a dietary intervention group (DG: n=39),
      receiving approximately 1200 mg of calcium and 7.5 microg of vitamin D3 per day
      via fortified dairy products and attending biweekly dietary and lifestyle
      intervention sessions; a calcium supplemented group (CaG: n=26) receiving a total
      of 1200 mg calcium per day; and a control group who continued with their usual
      diet (CG: n=36). Dietary, physical activity, anthropometric, body composition and
      distribution (based on DXA) data were collected at baseline and after 12 months
      of intervention. RESULTS: No significant differences were observed in the mean 12
      month changes in certain anthropometric (i.e. weight, BMI) and DXA (i.e. total
      body fat and lean mass) indices between groups. However, the DG was found to have
      a lower decrease in mid-arm muscle circumference (P<0.001) and a lower increase
      in the sum of skinfolds' thickness (P=0.042) compared with the CaG and the CG.
      Furthermore, the DG was also found to have a greater decrease in the percentage
      of legs' fat mass (P=0.025) and a higher increase in the percentage of legs' lean
      mass (P=0.012) compared with the two other groups. CONCLUSION: The application of
      a holistic intervention approach combining nutrition and lifestyle counseling
      with consumption of fortified dairy products for 12 months was found to have
      favourable changes in certain anthropometric and body composition indices
      compared to calcium supplementation alone.

PMID- 19118957
TI  - Intestinal intussusception in elderly patients.
AB  - Intussusception is the most common cause of bowel obstruction in children, but it
      is a very rare cause of bowel obstruction in the elderly. Diagnosis is based on a
      high index of suspicion, complete anamnestic recall, physical examination, and
      imaging modalities. We find abdominal CT scans to be highly sensitive and
      accurate for making the diagnosis. Treatment of intussusception in adults is
      always surgical. Segmental bowel resection must be performed. The extent of
      resection should include any nonviable bowel as well as the leading point of the
      intussusception. We present a case of an 82-year-old patient with ileo-cecal
      intussusception, followed by a discussion of the diagnostic and therapeutic
      options.

PMID- 19118958
TI  - Progestogen use in women approaching the menopause and breast cancer risk.
AB  - OBJECTIVE: Progestogens, particularly synthetic progestins, are widely used to
      contrast the clinical consequences of the relative hyperestrogenism that
      characterizes the years preceding the menopause. As a large body of data on
      postmenopausal hormone therapy (HT) demonstrates that the addition of synthetic
      progestins to estrogen increases the breast cancer risk compared to estrogen
      alone, it is important to evaluate if the use of progestogens in premenopausal
      years is associated with the risk of breast cancer. METHODS: Main literature data
      on the association with breast cancer risk of progestogens, either used alone in
      premenopausal years or added to estrogen in postmenopausal HT, were reviewed.
      RESULTS: Available data suggest that long-term current use of progestogens in
      premenopausal women after the age of 40 years can increase the risk of breast
      cancer. Consistently with the data on postmenopausal HT, the risk increase is
      higher for lobular cancer than for ductal cancer. CONCLUSIONS: The most important
      and widely accepted indications to the use of progestogens in the years preceding
      the menopause are anovulatory menstrual disorders, for which a limited period of
      treatment is generally sufficient. Awaiting for further data, when using
      progestogens for longer periods to treat other problems (endometriosis, cyclical
      mastalgia, etc.), the possibility of increased breast cancer risk and clinical
      benefits have to be weighed. Anyway, as micronized progesterone and
      dydrogesterone, at least when they were used in postmenopausal HT, seem to have,
      according to a large observational study, a safer risk profile on the breast, the
      preferential use of these preparations could be suggested.

PMID- 19118959
TI  - Synchronous laryngeal squamous cell carcinoma and Hodgkin lymphoma of the head
      and neck region.
AB  - During the pathologic examination of neck dissection specimens, unexpected
      findings may occasionally be encountered. Such findings include the presence of a
      second primary tumor or a chronic infectious or inflammatory disease. We report a
      case of a 65-year-old man who underwent a supracricoid partial laryngectomy and
      bilateral neck dissection for squamous cell carcinoma of the larynx.
      Histopathologic examination of the larynx revealed well-differentiated squamous
      cell carcinoma, but examination of the neck dissection specimen revealed a mixed
      cellularity subtype of classical Hodgkin lymphoma.

PMID- 19118960
TI  - A pilot study on the changes in immunity after ACTH therapy in patients with West
      syndrome.
AB  - Adrenocorticotropic hormone (ACTH) has been the first-line drug for the treatment
      of West syndrome, although the therapy has various adverse effects. ACTH
      depresses resistance to a variety of bacterial, viral, protozoal, and fungal
      agents. The timing of the various vaccinations is delayed after ACTH therapy in
      Japan, because the immune system is believed to be affected for approximately 6
      months. However, the duration of the effect of ACTH on the immune system is not
      known. Therefore, we examined changes in the immunity levels before and after
      ACTH therapy. We measured white blood cell counts, lymphocyte counts, T/B cell
      counts, CD4(+) and CD8(+) T cell counts, CD 4/8 ratio, lymphocyte blastoid
      transformation by PHA or Con-A, and the levels of IgA, IgM, and IgG before,
      immediately after, and 1, 3, 6, and 12 months after ACTH therapy. The lymphocyte
      counts and CD4(+) T cell counts were significantly decreased immediately after
      and at 1 and 3 months after the therapy, and did not return to the previous
      levels even at 6 months and 12 months after ACTH treatment; however, these levels
      returned to within normal limits (within the 95% confidence interval).
      Immunoglobulin levels did not change after the ACTH therapy. Helper T cells were
      more depressed than cytotoxic T cells after ACTH therapy.

PMID- 19118961
TI  - Intracerebral cell transplantation therapy for murine GM1 gangliosidosis.
AB  - We performed a cell transplantation study to treat the brain involvement in
      lysosomal storage diseases. We used acid beta-galactosidase knock-out mice (BKO)
      from C57BL/6 as recipients. To minimize immune responses, we used cells derived
      from transgenic mice of C57BL/6 overexpressing the normal human beta
      galactosidase. Fetal brain cells (FBC), bone marrow-derived mesenchymal stem
      cells (MSC), and mixed FBC and MSC cells were prepared and injected into the
      ventricle of newborn BKO mouse brain. The mice were examined at 1, 2, 4, and 8
      weeks and 6 months after injection. In each experiment, the injected cells
      migrated into the whole brain effectively and survived for at least 8 weeks.
      Decrease in ganglioside GM1 level was also observed. FBC could survive for 6
      months in recipient brain. However, the number of transplanted FBC decreased. In
      the brains of MSC- or mixed cell-treated mice, no grafted cells could be found at
      6 months. To achieve sufficient long-term effects on the brain, a method of
      steering the immune response away from cytotoxic responses or of inducing
      tolerance to the products of therapeutic genes must be developed.

PMID- 19118962
TI  - [Metronidazole-induced reversible cerebellar lesions and peripheral neuropathy].
AB  - INTRODUCTION: Metronidazole is a widely prescribed treatment for amoebic and
      anaerobic germ infections. Its neurologic toxicity is rare but can be serious.
      CASE REPORT: We report the case of a 27-year-old male patient, treated with
      metronidazole for a cerebral abscess. He presented with a cerebellar syndrome and
      peripheral neuropathy at a cumulative metronidazole dose of 60g. The MRI aspect
      of the cerebellar lesions in addition to their reversibility after treatment
      cessation led to the diagnosis of metronidazole induced neurologic toxicity.
      CONCLUSION: The occurrence of neurologic disorders in patients treated with
      metronidazole must suggest drug toxicity and lead to cessation of treatment.

PMID- 19118963
TI  - [An update on rickettsiosis].
AB  - Rickettsiae are strictly intracellular bacteria belonging to the Rickettsiaceae
      family. They are transmitted by various arthropods species, which are either
      vectors or reservoirs for the bacteria. The specific association between
      Rickettsieae and the vector are extensively studied, moreover Rickettsieae
      associated diseases are part of a continuously evolving field. Nevertheless, some
      rickettsiosis, such as epidemic typhus, have been described since the 16th
      century. Emerging diseases related to these bacteria are being investigated as
      well as new species, the implication of which is not always clear in human
      pathology when they are discovered. Some of these diseases are benign, others may
      be potentially fatal. Clinicians must therefore be aware of them. These issues
      are reviewed.

PMID- 19118964
TI  - [Urinary tract infections in Ain M'lila (Algeria). Antibiotic resistance of 239
      strains isolated between 2006 and 2007].

PMID- 19118965
TI  - TNF antagonists in the treatment of inflammatory bowel disease: results of a
      survey of gastroenterologists in the French region of Lorraine.
AB  - BACKGROUND AND OBJECTIVE: We conducted a survey of nonacademic
      gastroenterologists to evaluate the use of tumor necrosis factor (TNF)
      antagonists in inflammatory bowel disease (IBD). METHODS: A total of 100
      questionnaires were sent by mail to a representative sample of
      gastroenterologists practicing in the French region of Lorraine. RESULTS: Forty
      six practitioners responded to the survey, of whom 95.5% prescribed scheduled
      infliximab treatment. After 6 months of infliximab in combination with
      azathioprine, 55% then prescribed infliximab as monotherapy. A complete
      pretherapeutic assessment was performed by only one fourth of the
      gastroenterologists. When the PPD skin test measured 7 mm, nearly half of the
      physicians introduced anti-TNF therapy without chemoprophylaxis (versus only 2.4%
      when the diameter was 11 mm). In the event of quiescent Crohn's disease (CD)
      after 1 year of anti-TNF treatment, 35.7% stopped the drug. In refractory CD,
      72.7% prescribed infliximab as the first-line therapy (versus 27.3% who used
      adalimumab). In patients with urinary tract infection, 44.2% initiated
      antibiotics and delayed anti-TNF treatment, while 46.5% initiated anti-TNF
      therapy along with antibiotic therapy. CONCLUSION: This study is the first survey
      upon the use of TNF antagonists by nonacademic gastroenterologists, and the
      findings suggest that physicians using these drugs may require more information
      about the pretherapeutic assessment and management of the infectious risk.

PMID- 19118966
TI  - Prevention of relapse by mesalazine (Pentasa) in pediatric Crohn's disease: a
      multicenter, double-blind, randomized, placebo-controlled trial.
AB  - AIM: This study aimed to test the efficacy of mesalazine in maintaining remission
      in pediatric Crohn's disease (CD) following successful flare-up treatment.
      METHODS: In this double-blind, randomized, placebo-controlled trial, 122 patients
      received either mesalazine 50mg/kg per day (n=60) or placebo (n=62) for one year.
      Treatment allocation was stratified according to flare-up treatment (nutrition or
      medication alone). Recruitment was carried out over two periods, as the first
      period's results showed a trend favoring mesalazine. Relapse was defined as a
      Harvey-Bradshaw score more than or equal to 5. Time to relapse was analyzed using
      the Cox model. RESULTS: The one-year relapse rate was 57% (n=29) and 63% (n=35)
      in the mesalazine and placebo groups, respectively. We demonstrated a twofold
      lower relapse risk (P<0.02) in patients taking mesalazine in the medication
      stratum (first recruitment period), and a twofold higher risk in patients taking
      mesalazine in the nutrition stratum (second recruitment period), compared with
      the other groups. None of the children's characteristics, which differed across
      the two recruitment periods, accounted for the between-period variation in
      mesalazine efficacy. One serious adverse event was reported in each treatment
      group. CONCLUSION: Overall, mesalazine does not appear to be an effective
      maintenance treatment in pediatric CD.

PMID- 19118967
TI  - MR imaging of the small bowel in Crohn's disease.
AB  - MR and CT techniques optimized for small bowel imaging are playing an increasing
      role in the evaluation of small bowel disorders. Several studies have shown the
      advantage of these techniques over tradition barium fluoroscopic examinations
      secondary to improvements in spatial and temporal resolution combined with
      improved bowel distending agents. The preference of MR vs. CT has been
      geographical and based on expertise and public policy. With the increasing
      awareness of radiation exposure, there has been a more global interest in
      implementing techniques that either reduce or eliminate radiation exposure
      [Brenner DJ, Hall EJ. Computed tomography--an increasing source of radiation
      exposure. N Engl J Med 2007;357:2277-84]. This is especially important in
      patients with chronic diseases such as inflammatory bowel disease who may require
      multiple studies over a lifetime or in studies that require sequential imaging
      time points such as in assessment of gastrointestinal motility [Froehlich JM,
      Patak MA, von Weymarn C, Juli CF, Zollikofer CL, Wentz KU. Small bowel motility
      assessment with magnetic resonance imaging. J Magn Reson Imaging 2005;21:370-75].
      A recent study showed that certain subgroups of patients with Crohn's disease may
      be exposed to higher doses of radiation; those diagnosed at an early age, those
      with upper tract inflammation, penetrating disease, requirement of intravenous
      steroids, infliximab or multiple surgeries [Desmond AN, O'Regan K, Curran C, et
      al. Crohn's disease: factors associated with exposure to high levels of
      diagnostic radiation. Gut 2008;57:1524-29]. Therefore it has been suggested that
      techniques that can reduce or eliminate radiation exposure should be considered
      for imaging [Brenner DJ, Hall EJ. Computed tomography--an increasing source of
      radiation exposure. N Engl J Med 2007;357:2277-84]. Owing to the excellent
      softtissue contrast, direct multiplanar imaging capabilities, new ultrafast
      breath-holding pulse sequences, lack of ionizing radiation and availability of a
      variety of oral contrast agents, MR is well suited to play a critical role in the
      imaging of small bowel disorders. In this article we will review the technical
      issues related to the performance of MR enterography and enteroclysis and discuss
      the role and controversies of using MR in the assessment of inflammatory bowel
      disease.

PMID- 19118968
TI  - CT enterography: principles, technique and utility in Crohn's disease.
AB  - CT enterography is a modification of conventional CT technique optimized for the
      evaluation of small bowel. This technique utilizes multidetector scanners with
      high spatial and temporal resolution; multiplanar reconstructions; and large
      volumes of enteric contrast to provide bowel distension. This article discusses
      the essential principles of the exam and its use in the evaluation of Crohn's
      disease of the small bowel.

PMID- 19118969
TI  - Toxicity phenotype does not correlate with phylogeny of Cylindrospermopsis
      raciborskii strains.
AB  - Cylindrospermopsis raciborskii is a species of freshwater, bloom-forming
      cyanobacterium. C. raciborskii produces toxins, including cylindrospermopsin
      (hepatotoxin) and saxitoxin (neurotoxin), although non toxin-producing strains
      are also observed. In spite of differences in toxicity, C. raciborskii strains
      comprise a monophyletic group, based upon 16S rRNA gene sequence identities
      (greater than 99%). We performed phylogenetic analyses; 16S rRNA gene and 16S-23S
      rRNA gene internally transcribed spacer (ITS-1) sequence comparisons, and genomic
      DNA restriction fragment length polymorphism (RFLP), resolved by pulsed-field gel
      electrophoresis (PFGE), of strains of C. raciborskii, obtained mainly from the
      Australian phylogeographic cluster. Our results showed no correlation between
      toxic phenotype and phylogenetic association in the Australian strains. Analyses
      of the 16S rRNA gene and the respective ITS-1 sequences (long L, and short S)
      showed an independent evolution of each ribosomal operon. The genes putatively
      involved in the cylindrospermopsin biosynthetic pathway were present in one locus
      and only in the hepatotoxic strains, demonstrating a common genomic organization
      for these genes and the absence of mutated or inactivated biosynthetic genes in
      the non toxic strains. In summary, our results support the hypothesis that the
      genes involved in toxicity may have been transferred as an island by processes of
      gene lateral transfer, rather than convergent evolution.

PMID- 19118970
TI  - Quantitative determination of zidovudine diaryl phosphate triester pro-drugs in
      rat plasma by high-performance liquid chromatography-electrospray ionization
      tandem mass spectrometry.
AB  - A rapid, simple, and sensitive high-performance liquid
      chromatography/electrospray ionization tandem mass spectrometry (HPLC/ESI-MS/MS)
      method was developed and validated for quantitative analysis of 3'-azido-3'
      deoxythymidine (zidovudine, AZT) diaryl phosphate triester pro-drugs, in rat
      plasma using 2',3'-dideoxy-2'3'-didehydrothymidine (d4T) as internal standard
      (IS). The analytes were extracted from rat plasma with methanol after protein
      precipitation. The compounds were separated by HPLC with gradient elution (on a
      Shim-pack VP-ODS C(18) analytical column using a mobile phase of methanol/10mM
      ammonium acetate). All the analytes were detected in positive ion mode using
      multiple reaction monitoring (MRM). The method was validated and the specificity,
      linearity, lower limit of quantitation (LLOQ), precision, accuracy, recoveries
      and stability were determined. LLOQs were 10 ng mL(-1) for M1, M2, M3, M4, and
      M5, respectively. Correlation coefficient (r) values for the linear range of 10
      10,000 ng mL(-1) were greater than 0.999 for all the analytes. The intra-day and
      inter-day precision and accuracy were higher than 7.13%. The relative and
      absolute recovery was above 72% and no matrix effects were observed for all the
      analytes. This validated method provides a modern, rapid, and robust procedure
      for the pharmacokinetic studies of the pro-drugs after intravenous administration
      to rats. Some important results of AZT diaryl phosphate triester pro-drugs
      concerning chemical effect on pharmacokinetic performance are also studied.

PMID- 19118971
TI  - Process evaluation of a self-management cognitive program for persons with
      multiple sclerosis.
AB  - OBJECTIVE: Cognitive changes are highly prevalent in multiple sclerosis (MS)
      however evidence-based research on cognitive rehabilitation programs for this
      population is only beginning to emerge. This article presents results from a
      process evaluation of a group-based, self-management cognitive intervention
      program developed specifically for people with MS. METHODS: Quantitative and
      qualitative data were collected using focus group interviews, facilitator
      reflection notes, and program evaluations. The data were used to identify the
      strengths and limitations of the program and to document recommendations for
      future development. Forty-one individuals met eligibility criteria and were
      enrolled in the program. RESULTS: Overall, participants reported that the program
      had a positive impact on their ability to manage cognitive symptoms. Program
      components that contributed to successful application of cognitive management
      strategies included increasing participant's knowledge of cognitive changes,
      problem-solving through cognitive challenges, practicing strategies through
      homework assignments, and conducting the program in a group format. Participants
      recommended that caregivers be included in future programs. CONCLUSION: Both
      content and structural components of the program facilitated participants'
      ability to manage cognitive changes and contributed to behavior changes made by
      the participants. PRACTICE IMPLICATIONS: This study points to the benefits of
      incorporating self-management programs into the cognitive rehabilitation process
      in MS.

PMID- 19118972
TI  - Fatigue communication at the out-patient clinic of Rheumatology.
AB  - OBJECTIVE: To describe nurse-patient and rheumatologist-patient interaction in
      fatigue communication at the rheumatology out-patient clinic. METHODS:
      Consultations of 20 rheumatoid arthritis (RA) patients with the nurse specialist
      and the rheumatologist were videotaped and analysed using the Medical Interview
      Aural Rating Scale (MIARS). Subsequently, patients were asked to fill out a
      concern questionnaire asking how worried they felt and how satisfied they were
      with attention given by both healthcare professionals. Finally, patients were
      interviewed on reasons for being not or not completely satisfied with the care
      received. RESULTS: Fatigue was discussed in 42% of the rheumatologists'
      consultations and 83% of the nurse specialists' consultations. RA patients more
      often used implicit cues instead of explicit concerns related to fatigue. Almost
      72% of the patients felt worried about fatigue and in general they were more
      satisfied with the nurse specialist's attention to fatigue than with the
      attention from the rheumatologist. CONCLUSION: Fatigue is not structurally
      communicated at the rheumatology out-patient clinic and exploring and
      acknowledging communication techniques can help patients to express their
      concerns about fatigue. PRACTICE IMPLICATIONS: Healthcare professionals must
      recognise fatigue as a severe problem for RA patients and start the conversation
      on fatigue instead of waiting for the patient to mention fatigue spontaneously.

PMID- 19118973
TI  - Assessing risk communication in breast cancer: are continuous measures of patient
      knowledge better than categorical?
AB  - OBJECTIVE: To compare the performance of categorical and continuous measures of
      patient knowledge in the context of risk communication about breast cancer, in
      terms of statistical and clinical significance as well as efficiency. METHODS:
      Twenty breast cancer patients provided estimates of 10-year mortality risk before
      and after their oncology visit. The oncologist reviewed risk estimates from
      Adjuvant!, a well-validated and commonly used prognostic model. Using the
      Adjuvant! estimates as a gold standard, we calculated how accurate the patient
      estimates were before and after the visit. We used three novel continuous
      measures of patient accuracy, the absolute bias, Brier, and Kullback-Leibler
      scores, and compared them to a categorical measure in terms of sensitivity to
      intervention effects. We also calculated the sample size required to replicate
      the primary study using the categorical and continuous measures, as a means of
      comparing efficiency. RESULTS: In this sample, the Kullback-Leibler measure was
      most sensitive to the intervention effects (p=0.004), followed by Brier and
      absolute bias (both p=0.011), and finally the categorical measure (0.125). The
      sample size required to replicate the primary study was 18 for the Kullback
      Leibler measure, 23 for absolute bias and Brier, and 37 for the categorical
      measure. CONCLUSIONS: The continuous measures led to more efficient sample sizes
      and to rejection of the null hypothesis of no intervention effect. However, the
      difference in sensitivity of the continuous measures was not statistically
      significant, and the performance of the categorical measure depends on the
      researcher's categorical cutoff for accuracy. Continuous measures of patient
      accuracy may be more sensitive and efficient, while categorical measures may be
      more clinically relevant. PRACTICE IMPLICATIONS: Researchers and others
      interested in assessing the accuracy of patient knowledge should weigh the trade
      offs between clinical relevance and statistical significance while designing or
      evaluating risk communication studies.

PMID- 19118974
TI  - [Alveolar echinococcosis].

PMID- 19118975
TI  - Treatment of elopement in individuals with developmental disabilities: a
      systematic review.
AB  - We reviewed studies involving the treatment of elopement in individuals with
      developmental disabilities. Systematic searches of three electronic databases,
      journals, and reference lists identified 10 studies meeting the inclusion
      criteria. These studies were evaluated in terms of: (a) participants, (b)
      procedures used to assess elopement, (c) intervention procedures, (d) results of
      the intervention, and (e) certainty of evidence. Across the 10 studies,
      intervention was provided to a total of 53 participants aged 3-47 years.
      Assessment procedures included anecdotal staff reports, participant interviews,
      direct observation, and modified analog functional analysis. Intervention
      approaches included differential reinforcement, extinction, functional
      communication training, response blocking, non-contingent reinforcement, shaping,
      and scheduled exercise. Positive outcomes were reported in 80% of the reviewed
      studies. The evidence base suggests that function-based assessment (e.g.
      functional analysis procedures) and function-based treatments (e.g. functional
      communication training) may be most effective in the treatment of elopement in
      this population. Directions for future research are offered.

PMID- 19118976
TI  - A signal theory approach to support vector classification: the sinc kernel.
AB  - Fourier-based regularisation is considered for the support vector machine
      classification problem over absolutely integrable loss functions. By invoking the
      modest assumption that the decision function belongs to a Paley-Wiener space, it
      is shown that the classification problem can be developed in the context of
      signal theory. Furthermore, by employing the Paley-Wiener reproducing kernel,
      namely the sinc function, it is shown that a principled and finite kernel hyper
      parameter search space can be discerned, a priori. Subsequent simulations
      performed on a commonly-available hyperspectral image data set reveal that the
      approach yields results that surpass state-of-the-art benchmarks.

PMID- 19118977
TI  - On periodic solutions of neural networks via differential inclusions.
AB  - Discontinuous dynamical systems, especially neural networks with discontinuous
      activation functions, arise in a number of applications and have received
      considerable research attention in recent years. However, there still remain some
      fundamental issues to be investigated, for instance, how to define the solutions
      of such discontinuous systems and what conditions can guarantee the existence and
      stability of the solutions. In this paper, based on the concept of Filippov
      solution, the dynamics of a general class of neural networks with discontinuous
      activation functions is investigated. Sufficient conditions are obtained to
      ensure the existence and stability of the unique periodic solution for the neural
      networks by using the differential inclusions theory, the Lyapunov-Krasovskii
      functional method and linear matrix inequality (LMI) technique. Two numerical
      examples are given to illustrate the theoretical results.

PMID- 19118978
TI  - A cone-beam CT based technique to augment the 3D virtual skull model with a
      detailed dental surface.
AB  - Cone-beam computed tomography (CBCT) is used for maxillofacial imaging. 3D
      virtual planning of orthognathic and facial orthomorphic surgery requires
      detailed visualisation of the interocclusal relationship. This study aimed to
      introduce and evaluate the use of a double CBCT scan procedure with a modified
      wax bite wafer to augment the 3D virtual skull model with a detailed dental
      surface. The impressions of the dental arches and the wax bite wafer were scanned
      for ten patient separately using a high resolution standardized CBCT scanning
      protocol. Surface-based rigid registration using ICP (iterative closest points)
      was used to fit the virtual models on the wax bite wafer. Automatic rigid point
      based registration of the wax bite wafer on the patient scan was performed to
      implement the digital virtual dental arches into the patient's skull model.
      Probability error histograms showed errors of < or =0.22 mm (25% percentile), <
      or =0.44 mm (50% percentile) and < or =1.09 mm (90% percentile) for ICP surface
      matching. The mean registration error for automatic point-based rigid
      registration was 0.18+/-0.10 mm (range 0.13-0.26 mm). The results show the
      potential for a double CBCT scan procedure with a modified wax bite wafer to set
      up a 3D virtual augmented model of the skull with detailed dental surface.

PMID- 19118979
TI  - Interictal epileptogenic fast oscillations on neonatal and infantile EEGs in
      hemimegalencephaly.
AB  - PURPOSE: Hemimegalencephaly is an epileptic encephalopathy which presents during
      the neonatal period. Our aims are to analyze interictal fast oscillations and EEG
      patterns in neonates and infants with hemimegalencephaly. METHODS: We collected
      scalp EEGs and applied multiple band frequency analysis (MBFA) to analyze
      frequency and power of interictal fast oscillations (FOs). RESULTS: We studied 18
      scalp EEGs in 7 patients with catastrophic epilepsy secondary to
      hemimegalencephaly, between 3 days and 24 months of age. Maximum frequency of FOs
      (22-57 Hz; mean, 42 Hz) on the hemimegalencephalic side was significantly higher
      than those (8-27 Hz; mean, 18 Hz) in the unaffected side (p<0.05). Differences in
      maximum FOs remained within 1-8 Hz (mean, 3 Hz) across consecutive EEGs. We found
      four EEG patterns: (1) suppression burst pattern (7 EEGs, 6 patients), (2)
      continuous triphasic complex pattern (5 EEGs, 3 patients), (3) continuous high
      amplitude slow waves with spikes (3 EEGs, 2 patients) and (4) frequent spike and
      slow waves (3 EEGs, 2 patients). Five patients with multiple EEG recordings
      showed changing EEG patterns. CONCLUSION: We confirmed the interictal
      epileptogenic FOs in neonatal EEGs of patients with hemimegalencephaly. The
      frequency of epileptogenic FOs remains stable from the neonates through
      increasing age while the patterns of EEG changed during brain maturation.

PMID- 19118980
TI  - Proton MR spectroscopy of metabolite concentrations in temporal lobe epilepsy and
      effect of temporal lobe resection.
AB  - PURPOSE: To use proton Magnetic Resonance Spectroscopy (MRS) to measure in vivo
      temporal lobe GABA and glutamate plus glutamine (GLX) concentrations in patients
      with temporal lobe epilepsy (TLE) attributable to unilateral hippocampal
      sclerosis (HS) before and following anterior temporal lobe resection (ATLR).
      METHODS: We obtained quantitative short echo time MRS in both temporal lobes of
      15 controls and 16 patients with TLE and HS, and repeat spectra in 10 patients
      after ATLR. We measured the concentrations of N-acetyl aspartate+N-acetyl
      aspartyl-glutamate (NAAt), creatine plus phosphocreatine (Cr), and
      glutamate+glutamine (GLX) using a metabolite-nulled sequence designed to minimize
      macromolecule artifact. GABA concentrations were measured using a previously
      described double quantum filter. RESULTS: In patients with TLE, NAAt/Cr was
      reduced in ipsilateral and contralateral temporal lobes. No significant variation
      in GLX/Cr or GABA+/Cr was evident in any group although GABA+/Cr was highest in
      the ipsilateral temporal lobe in TLE. After ATLR there was a trend to
      normalization of NAAt/Cr in the contralateral temporal lobe but no change in
      individual metabolite concentrations, GLX/Cr or GABA+/Cr compared to pre-surgery
      levels. DISCUSSION: Temporal lobe epilepsy was associated with bilateral
      reduction in NAAt/Cr but not significant abnormality in GABA+/Cr or GLX/Cr.
      Normalization of NAAt/Cr in the contralateral temporal lobe was seen following
      successful ATLR.

PMID- 19118981
TI  - Dichotomous effect of ultraviolet B on the expression of corneodesmosomal enzymes
      in human epidermal keratinocytes.
AB  - BACKGROUND: The stratum corneum chymotryptic enzyme (SCCE) and the stratum
      corneum tryptic enzyme (SCTE) are serine proteases of the kallikrein family that
      are encoded by the KLK7 and KLK5 genes, respectively. They might play a role in
      desquamation by cleaving corneodesmosomal proteins. Their activities are
      regulated by lympho-ephithelial Kazal-type related inhibitor (LEKTI), which is
      encoded by the SPINK5 gene. OBJECTIVE: To elucidate the role of these molecules
      in ultraviolet B (UVB)-induced desquamation of the stratum corneum, we examined
      the effect of UVB irradiation on the expression of these enzymes in human
      epidermal keratinocytes. METHODS: The effects of UVB on SCCE (KLK7), SCTE (KLK5)
      and LEKTI (SPINK5) expression in keratinocytes were estimated using HaCaT cells,
      normal human epidermal keratinocytes and a reconstructed human epidermis model.
      RESULTS: UVB irradiation significantly reduced the expression of SPINK5 and
      increased the expression of KLK5 and KLK7, as assessed by real-time PCR, and
      reduced the expression of LEKTI and increased the expression of SCTE and SCCE by
      Western blotting and/or immunofluorescence analysis. Protease activity, as
      assessed by in situ zymography, was enhanced in the epidermis following exposure
      to UVB irradiation compared with sham-irradiated epidermis. CONCLUSION: These
      results suggest that reduced expression of LEKTI and increased expression of SCCE
      and SCTE in human epidermal keratinocytes after UVB irradiation may contribute to
      desquamation of the stratum corneum.

PMID- 19118982
TI  - Antimicrobial properties of shiitake mushrooms (Lentinula edodes).

PMID- 19118983
TI  - Belgian Schizophrenia Outcome Survey - results of a 2-year naturalistic study in
      patients stabilised on monotherapy with olanzapine, risperidone or haloperidol.
AB  - OBJECTIVES: This Schizophrenia Outcome Survey compared medical costs,
      psychopathology and adverse events in outpatients for 2 years following
      hospitalisation for an acute schizophrenic episode. METHODS: Adults stabilised
      with haloperidol, olanzapine or risperidone entered this observational study
      <or=1 month after discharge and were assessed at baseline, 3, 6, 12, 18 and 24
      months using Brief Psychiatric Rating Scale (BPRS), Clinical Global Impression
      (CGI), Global Assessment of Functioning and adverse events reporting. RESULTS:
      Among 323 patients (haloperidol 32, olanzapine 149, risperidone 142), baseline
      characteristics were similar in the olanzapine and risperidone groups, except for
      more first episodes in the risperidone group (p=0.01). Haloperidol patients were
      more often single and institutionalised, less educated, had more residual
      schizophrenia, were longer hospitalised in the previous year, took more
      corrective and psychotropic drugs and had more extrapyramidal symptoms (EPS) and
      gynaecomastia (all significantly). Sixty-eight percent of patients completed a 2
      year follow-up. In all groups, CGI and GAF improved during the first 3 months
      (both p<0.0001) while BPRS deteriorated in the first year (all within group
      changes p<0.05, between group changes NS) before it stabilised. There were no
      significant differences in hospitalisations and no change in social profile. At
      the last visit, 66% of haloperidol (p<0.01), 35% of olanzapine (NS) and 39% (NS)
      of risperidone patients had >or=1 EPS; 69% (p<0.013), 40 and 44%, respectively,
      had >or=1 sexual problem (NS). Mean weight gain was 0.4 (NS), 2.6 (p<0.05) and
      2.6 kg (p<0.05), respectively. CONCLUSIONS: In this naturalistic study, treatment
      allocation might have introduced a bias in the interpretation of efficiency
      results, but olanzapine and risperidone caused less EPS than haloperidol during 2
      years of outpatient follow-up.

PMID- 19118984
TI  - Obsessive-compulsive personality disorder traits and personality dimensions in
      parents of children with obsessive-compulsive disorder.
AB  - PURPOSE: To compare patterns of temperament and character and the prevalence of
      Obsessive-Compulsive Personality Disorder (OCPD) and OCPD traits in parents of
      children with OCD and parents of healthy controls. METHODS: TCI and SCID-II were
      administered to 63 parents of 32 children with OCD and 63 parents of age- and sex
      matched controls with no psychiatric diagnosis. Interviewers were not blind to
      proband status. Personality dimension scores and frequencies of OCPD criteria in
      both groups were compared after excluding parents with a diagnosis of OCD.
      Relationships between TCI dimensions and OCPD symptoms in parents and the
      clinical characteristics of OCD children were also studied. RESULTS: Parents of
      OCD children presented significantly higher scores in harm avoidance and lower
      scores in self-directedness, cooperativeness and reward dependence than parents
      of healthy children. A higher incidence of OCPD was found in parents of probands
      (p<0.02). Hoarding, perfectionism and preoccupation with details were
      significantly more frequent in parents of OCD children. Counting, ordering and
      cleaning compulsions in OCD children predicted elevated odds of perfectionism and
      rigidity in their parents. CONCLUSIONS: The existence of the dimensional
      personality profile associated with OCD in parents of children with OCD and the
      higher number of OCPD criteria in these parents in comparison to parents of
      healthy children highlight the importance of the role of personality factors in
      familial OCD.

PMID- 19118985
TI  - 5-HT(1A) receptor and 5-HTT binding during the menstrual cycle in healthy women
      examined with [(11)C] WAY100635 and [(11)C] MADAM PET.
AB  - The aim of the present study was to explore the effects of the menstrual cycle
      phases on 5-HT(1A) receptor and 5-HTT binding potentials (BPs) in healthy women
      by using positron emission tomography (PET). Women were investigated in the
      follicular and luteal phase of the menstrual cycle with radioligands
      [(11)C]WAY10035 (n=13) and [(11)C]MADAM (n=8) to study 5-HT(1A) and 5-HTT BPs.
      The BPs values were quantified using the simplified reference tissue model. The
      phases of the menstrual cycle were characterized by transvaginal ultrasound (TSV)
      and plasma levels of hormones estradiol (E(2)), progesterone (P(4)), follicle
      stimulating hormone (FSH) and luteinizing hormone (LH).The 5-HT(1A) receptor and
      5-HTT BPs did not significantly differ between follicular and luteal phases in
      any of the investigated regions. There were no significant correlations between
      the change in E(2) or P(4) values with the change in 5-HT(1A) receptor or 5-HTT
      BPs. The results provide principally a new in vivo finding in human female
      biology, suggesting the absence of influence of menstrual cycle phase on 5-HT(1A)
      receptors or 5-HTT. The finding however does not preclude that gonadal hormones
      differentially influence central serotonin system inwomen and men, which might
      contribute to gender differences in serotonin-associated disorders.

PMID- 19118986
TI  - Adsorption of bovine serum albumin on fused silica: Elucidation of protein
      protein interactions by single-molecule fluorescence microscopy.
AB  - The adsorption of bovine serum albumin (BSA) on fused silica at pH 4.7 was
      studied at the single molecules level by total-internal-reflection fluorescence
      microscopy. This pH value was the isoelectric point of BSA. At low [BSA] of 20pM,
      protein molecules adsorbed as monomers. At intermediate [BSA] of 500pM, protein
      molecules adsorbed as clusters of about five monomers on average. Both monomers
      and clusters had adsorption rate coefficients of the order 10(-7)ms(-1) and
      desorption rate coefficients of about 2x10(-2)s(-1). The respective steady-state
      coverage was about 10x higher than that at neutral pH, presumably because of the
      more favorable BSA-silica electrostatics. At pH 4.7 and with [BSA] higher than
      100nM, adsorption begot further adsorption to produce nonlinear isotherms. The
      coverage at 1microM BSA was 2.5x that of the linearly extrapolated coverage. This
      suggests that at pH 4.7, solute-adsorbate affinity was the dominant factor that
      explains the enhanced adsorption observed in ensemble measurements.

PMID- 19118987
TI  - Spectroscopic studies on the interaction of cationic surfactants with bovine
      serum albumin.
AB  - The interaction of the cationic surfactant cetyltrimethylammonium bromide (CTAB)
      with bovine serum albumin (BSA), a globular protein, has been studied by small
      angle neutron scattering (SANS), fluorescence and circular dichroism (CD). SANS
      measurements show that at low [CTAB] the protein shows a native-like behavior. On
      the other hand, at high [CTAB], surfactant molecules result in the formation of a
      fractal structure representing a 'necklace model' of micelle-like clusters
      randomly distributed along the polypeptide chain. The overall size of the complex
      increases and the fractal dimension decreases on increasing the surfactant
      concentration. The size of the micelle-like clusters does not show any
      considerable change while the number of such clusters and their aggregation
      number increases with increasing [CTAB]. Some extrapolatory experiments were
      performed with tetradecyltrimethylammonium bromide (TTAB) and the surfactant was
      found to behave similarly leading to an increase in the size of protein along the
      semi-major axis at low concentrations and formation of a fractal structure at
      high concentrations. The fluorescence studies undertaken were found to be
      consistent with the SANS measurements. Native-like behavior of the protein mixed
      with low concentration of the surfactant was also concluded from the circular
      dichroism (CD) spectra where the spectra in presence of high [CTAB] could not be
      monitored because of high dynode voltage.

PMID- 19118988
TI  - Structural and calorimetrical studies of the effect of different aminoglycosides
      on DPPC liposomes.
AB  - The effects of tobramycin, spectinomycin and streptomycin on 1,2-dipalmitoyl-sn
      glycero-3-phosphocholine (DPPC)/water vesicle system were studied by using
      differential scanning calorimetry (DSC) and simultaneous small- and wide-angle X
      ray scattering (SWAXS) in the 0-1 lipid/aminoglycoside molar range. The changes
      in enthalpy between the thermally adjacent phases are decreased, but the pace of
      decrease is totally different for the three investigated AGs. The alterations in
      the lamellar arrangement and the chain packing are rather tendentious and are
      extended by increased AG concentrations depending on the type of the AG. In the
      case of tobramycin and streptomycin, still sharp Bragg peaks of SAXS curves shift
      to smaller values of the scattering variable, while spectinomycin results in an
      entire loss of multilayer correlation representing an increased amount of unbound
      bilayers.

PMID- 19118989
TI  - Surface properties of new virginiamycin M(1) derivatives.
AB  - Three kinds of derivatives of the M(1) factor of virginiamycin have been
      synthesised: esters with long chain fatty acids, oximes with modified polar amino
      acids and bis-derivatives with both the ester and oxime function. The study of
      the surface tension time dependence of M(1) and its derivatives has shown that it
      is necessary to enhance simultaneously the hydrophobicity and the hydrophilicity
      of M(1) to render M(1) surface-active. A structure/function relationship study of
      the surface-active bis-derivatives has shown that enhancing the hydrophobicity of
      the molecule led to slower adsorption kinetics, higher stability of the
      monolayers formed and a better capacity to penetrate a membrane model. The
      repulsive electrostatic forces due to the presence of charges on the amino acids
      linked to M(1) lead to higher surface tensions, a greater molecular area at the
      interface and lower penetration into a membrane model. This study has
      demonstrated that modifying systematically the hydrophobicity and hydrophilicity
      of a non surface-active molecule allows the production of surface-active
      derivatives.

PMID- 19118990
TI  - Breathing with your belly: abdominal exhalation, loco-ventilatory integration and
      size constraints on locomotion in small mammals.
AB  - In mammals, diaphragmatic contractions control inhalation while contraction of
      some thoracic hypaxial muscles and the transversus abdominis muscle contribute to
      exhalation. Additional thoracic hypaxial muscles are recruited as accessory
      ventilatory muscles to improve inhalation and exhalation during locomotion.
      However, the contribution of abdominal hypaxial muscles to resting and locomotor
      ventilation is little understood in mammals and loco-ventilatory integration has
      not been studied in small basal mammals. We show for the first time that all of
      the abdominal hypaxial muscles actively contribute to both resting and locomotory
      ventilation in mammals but in a size-dependent manner. In large opossums
      (Didelphis), hypaxial muscles exhibit uniform mild tonus during resting
      ventilation (pressurizing the gut to aid in exhalation) and shift to phasic
      bursts of activity during each exhalation during locomotion. Smaller opossums
      (Monodelphis) actively exhale by firing the abdominal hypaxial muscles at
      approximately 10Hz at both rest and at preferred locomotor speeds. Furthermore,
      the large opossums entrained ventilation to limb cycling as speed increased while
      the small opossums entrained limb cycling to the resting ventilation rate during
      locomotion. Differences in these species are related to size effects on the
      natural frequency of the ventilatory system and increasing resting ventilation
      rates at small size. Large mammals, with lower resting ventilation rates, can
      increase ventilatory rates during locomotion, while the high resting ventilation
      rates of small mammals limits their ability to increase ventilation rates during
      locomotion. We propose that increase in mammalian body size during the Cenozoic
      may have been an adaptation or exaptation to overcome size effects on ventilation
      frequency.

PMID- 19118991
TI  - Synergy research: vitamins and secondary plant components in the maintenance of
      the redox-homeostasis and in cell signaling.
AB  - The maintenance of the redox-homeostasis is an essential task of antioxidants.
      Reactive oxygen species (ROS) formed during oxidative stress can potentially
      damage the normal cellular functions and support pathological processes like
      atherosclerosis in vessels or malignant growth in other tissues, but also the
      aging process. However, recent findings link ROS also to cell survival and/or
      proliferation, which revolutionises the age-old dogmatic view of ROS being
      exclusively involved in cell damage and death. Low concentrations of
      hydrogenperoxide e.g. are involved in cell signaling and can activate mitogen
      activated kinases (MAPK) to initiate cell growth. Nutritional antioxidants like
      vitamin C or E can promote endothelial cell growth, but can also inhibit growth
      of muscle cells, and influence MAPK. Thus, keeping the redox-homeostasis in a
      steady state especially in the context of tissue regeneration appears to be more
      important than previously known and seems to be a controlled synergistic action
      of antioxidants and ROS. The present review summarizes the properties and
      functions of ROS and nutritional antioxidants like the vitamins C and E, and
      polyphenols in redox-homeostasis. Their relevance in the treatment of various
      diseases is discussed in the context of a multitarget therapy with nutraceuticals
      and phytotherapeutic drugs.

PMID- 19118992
TI  - Human milk arachidonic acid and docosahexaenoic acid contents increase following
      supplementation during pregnancy and lactation.
AB  - INTRODUCTION: Docosahexaenoic acid (DHA) and arachidonic acid (AA) are important
      for neurodevelopment. Maternal diet influences milk DHA, whereas milk AA seems
      rather constant. We investigated milk AA, DHA and DHA/AA after supplementation of
      AA plus DHA, or DHA alone during pregnancy and lactation. SUBJECTS AND METHODS:
      Women were supplemented with AA+DHA (220mg each/day), DHA (220mg/day) or placebo
      during pregnancy and lactation. Milk samples were collected at 2 (n=86) and 12
      weeks (n=69) postpartum. RESULTS: Supplementation of AA+DHA elevated milk AA
      (week 2, 14%; week 12, 23%) and DHA (43% and 52%) as compared to placebo. DHA
      tended to decrease milk AA and vice versa. Milk AA, DHA and DHA/AA decreased from
      2 to 12 weeks postpartum. CONCLUSIONS: Milk AA and in particular DHA are
      sensitive to maternal supplementation. It seems that maternal AA and notably DHA
      status decline with advancing lactation.

PMID- 19118993
TI  - Prevalence of airflow obstruction in patients attending a rapid access chest pain
      clinic.
AB  - BACKGROUND: Many UK hospitals have set-up specialised chest pain clinics to deal
      promptly and efficiently with cases of possible cardiac chest pain. It is
      possible that a proportion of patients attending these clinics will have a
      respiratory cause for their chest pain, or respiratory disease in addition to
      their cardiac pain. This study aimed to determine the prevalence of airflow
      obstruction, ischaemic heart disease and dual pathology in such patients.
      METHODS: Spirometry was performed on patients referred to a rapid access chest
      pain clinic over a 12-month period (target population of 400 patients). The main
      outcome measure was the prevalence of airflow obstruction (defined using
      spirometry), ischaemic heart disease and dual pathology. RESULTS: 405 subjects
      participated in the study. Abnormal spirometry was detected in 21% of patients
      (n=85). Airflow obstruction was the predominant lung function abnormality and was
      detected in 60 patients. Ischaemic heart disease was diagnosed in 21% of patients
      (n=85). Dual pathology was found in 4% of patients (n=17). CONCLUSIONS: Previous
      studies have reported a link between impaired lung function and future
      cardiovascular morbidity and mortality. This study suggests that airflow
      obstruction is an important alternative differential diagnosis in patients
      referred to a rapid access chest pain clinic. The identification of abnormal
      spirometry may help to better risk-stratify patients for future cardiovascular
      events and allow interventions to be instituted.

PMID- 19118994
TI  - Inhaled colistin as monotherapy for multidrug-resistant gram (-) nosocomial
      pneumonia: a case series.
AB  - BACKGROUND: Reports of patients with polymyxin-only susceptible gram-negative
      nosocomial pneumonia treated with inhaled, but without concurrent intravenous,
      colistin are rare. METHODS: Patients admitted in a tertiary 450-bed tertiary care
      centre during the period 05/01/2005-05/31/2007 and receiving colistin through
      nebulization, but not systemically, were included in this retrospective case
      series. RESULTS: Five patients (three with ventilator-associated pneumonia and
      two with nosocomial pneumonia) received colistin through nebulization without
      concomitant intravenous colistin. The isolated pathogens were Acinetobacter
      baumannii (three cases), Pseudomonas aeruginosa (one case) and the combination of
      Klebsiella pneumoniae, A. baumannii and P. aeruginosa (one case). They were
      susceptible only to colistin (three cases) or to colistin and gentamicin (two
      cases). Intravenous antimicrobial agents given concurrently were
      piperacillin/tazobactam, meropenem, ceftriaxone and ciprofloxacin; isolated
      pathogens were resistant to these agents. Four (80%) out of the five patients
      were cured, survived and were discharged. One patient died. No colistin-related
      adverse event was observed. CONCLUSIONS: The experience from this case series and
      other relevant recent reports suggest that treatment of pneumonia due to
      polymyxin-only susceptible gram-negative bacilli with inhaled colistin (without
      concurrent systemic administration) deserves further careful investigation.

PMID- 19118995
TI  - Cement based solidification/stabilization of arsenic-contaminated mine tailings.
AB  - Cement was used to solidify/stabilize the abandoned mine tailings contaminated
      primarily with arsenic (up to 88mg/kg) and lead (up to 35mg/kg).
      Solidified/stabilized (s/s) forms with a range of cement contents, 5-30wt%, were
      evaluated to determine the optimal binder content. Unconfined compression
      strength test (UCS), Korean standard leaching tests, toxicity characteristic
      leaching procedures (TCLP), and synthetic precipitation leaching procedure (SPLP)
      were used for physical and chemical characterization of the s/s forms. Addition
      of 5% cement was enough for the s/s forms to satisfy the UCS requirements
      (0.35MPa). The addition of 7.5% cement remarkably reduced the leachability of
      arsenic in tailings. However, that of lead tends to increase slightly with
      increase of cement content due to its amphoteric nature. The discussions were
      made for determination of optimal binder content and for results from different
      evaluation procedures.

PMID- 19118996
TI  - A QCM-D-based biosensor for E. coli O157:H7 highlighting the relevance of the
      dissipation slope as a transduction signal.
AB  - A biosensor for detection of viable Escherichia coli (E. coli) O157:H7 is
      developed using a quartz crystal microbalance with dissipation monitoring (QCM
      D). The detection platform is based on the immobilization of affinity purified
      polyclonal antibodies onto gold-coated QCM-D quartz crystals via a cysteamine
      self-assembled monolayer. QCM-D measurements conducted over a broad range of
      bacterial cell concentrations show that the optimal biosensor response is the
      initial slope of the dissipation shift as a function of elapsed time (D(slope)).
      A highly log-log linear response in the initial D(slope) is obtained for
      detection of E. coli O157:H7 over a wide range of cell concentrations from 3 x
      10(5) to 1 x 10(9)cells/mL. The prepared biosensor also exhibits a log-log linear
      working range from 10(7) to 10(9)cells/mL for E. coli K12 D21, a non-pathogenic
      model organism and further shows satisfactory selectivity using Bacillus
      subtilis. To our knowledge, this is the first study demonstrating the use of the
      initial D(slope) as a sensor response when using QCM-D technology.

PMID- 19118997
TI  - Electrowetting-based pH- and biomolecule-responsive valves and pH filters.
AB  - An electrowetting-based pH-responsive valve that uses a nonstandard
      electrochemical three-electrode system is proposed. The system comprises a gold
      valve electrode and an iridium electrode that act as the working and auxiliary
      electrodes, depending on the purpose, while an iridium oxide pH-sensitive
      electrode acts as the reference electrode. To make the valve open at pH higher
      than a threshold, the gold valve electrode is used as the working electrode and a
      voltage is applied to it with respect to the pH-sensitive reference electrode. To
      make the valve open at pH lower than the threshold, the gold valve electrode is
      used as the auxiliary electrode, while the iridium electrode is used as the
      working electrode. The wettability of the valve electrode is altered when a
      voltage is applied to it. When the pH of a solution crosses the threshold, the
      potential of the gold valve electrode exceeds a threshold potential because of
      the change in the potential of the pH-sensitive reference electrode.
      Consequently, the gold valve electrode becomes more hydrophilic, thereby allowing
      the solution to pass through the valve. Furthermore, by combining two valve
      electrodes, we realized a pH filter that allows solutions with pH within a
      limited range to pass through it. Urea- and glucose-responsive valves that opened
      at concentrations higher than the threshold could also be formed by immobilizing
      an enzyme on the pH-sensitive reference electrode.

PMID- 19118998
TI  - The expression of the novel CYP2W1 enzyme is an independent prognostic factor in
      colorectal cancer - a pilot study.
AB  - AIM: Cytochrome P450 (CYP) enzymes are important for drug metabolism. A novel
      cytochrome P450 enzyme, CYP2W1, has recently been identified. This enzyme is
      mainly found in foetal colon tissue and in tumour tissue. In this pilot study, we
      have investigated the expression of CYP2W1 in 162 tumours from patients with
      stages II and III colorectal cancer. METHODS: The expression of CYP2W1 enzyme was
      immunohistochemically detected using a polyclonal antibody. Staining intensity
      was defined using a visual grading scale from 0 to 3. Grades 0-2 were classified
      as low, and grade 3 was classified as high expression of CYP2W1. RESULTS: About
      64% of the tumours expressed a low level of CYP2W1-expression, and 36% expressed
      a high level. CYP2W1-expression was an independent prognostic factor for overall
      survival (p=0.007), where a high expression was associated with a worse clinical
      outcome. CONCLUSIONS: Immunohistochemically assessed expression of CYP2W1 is an
      independent prognostic factor in patients with stages II and III colorectal
      cancer.

PMID- 19118999
TI  - Natural orifice transluminal endoscopic surgery (N.O.T.E.S.) for oncologic
      disease.

PMID- 19119000
TI  - Biodiesel production from rice bran oil and supercritical methanol.
AB  - In this study, production of biodiesel from low cost raw materials, such as rice
      bran and dewaxed-degummed rice bran oil (DDRBO), under supercritical condition
      was carried out. Carbon dioxide (CO2) was employed as co-solvent to decrease the
      supercritical temperature and pressure of methanol. The effects of different raw
      materials on the yield of biodiesel production were investigated. In situ
      transesterification of rice bran with supercritical methanol at 30MPa and 300
      degrees C for 5 min was not a promising way to produce biodiesel because the
      purity and yield of fatty acid methyl esters (FAMEs) obtained were 52.52% and
      51.28%, respectively. When DDRBO was reacted, the purity and yield were 89.25%
      and 94.84%, respectively. Trans-FAMEs, which constituted about 16% of biodiesel,
      were found. They were identified as methyl elaidate [trans-9], methyl
      linoleaidate [trans-9, trans-12], methyl linoleaidate [cis-9, trans-12], and
      methyl linoleaidate [trans-9, cis-12]. Hydrocarbons, which constituted about 3%
      of the reaction product, were also detected.

PMID- 19119001
TI  - Releasing behavior of copper in recirculated bioreactor landfill.
AB  - The purpose of this study was to determine the releasing behavior of copper in
      municipal solid waste (MSW) in landfill with respect to refuse and leachate as an
      inseparable system. Two simulated bioreactor landfills, one with leachate
      recirculation and the other without, were operated in room temperature for 320
      days. Copper in refuse showed behaviors of staggered migration and retention,
      which corresponded with the degradation process of landfill obviously. The
      significant different amounts of Cu2+ leached out from refuse into leachate of
      two landfills were 24.74 mg and 118.53 mg after 320 days' operation,
      respectively. It also reflected the releasing behavior of copper in landfill
      refuse at different stage accordingly. The results confirmed that the refuse in
      landfill had high potential of secondary pollution after closure.

PMID- 19119002
TI  - Composting of animal manures and chemical criteria for compost maturity
      assessment. A review.
AB  - New livestock production systems, based on intensification in large farms,
      produce huge amount of manures and slurries without enough agricultural land for
      their direct application as fertilisers. Composting is increasingly considered a
      good way for recycling the surplus of manure as a stabilised and sanitised end
      product for agriculture, and much research work has been carried out in the last
      decade. However, high quality compost should be produced to overcome the cost of
      composting. In order to provide and review the information found in the
      literature about manure composting, the first part of this paper explains the
      basic concepts of the composting process and how manure characteristics can
      influence its performance. Then, a summary of those factors such as nitrogen
      losses (which directly reduce the nutrient content), organic matter humification
      and compost maturity which affect the quality of composts produced by manure
      composting is presented. Special attention has been paid to the relevance of
      using an adequate bulking agent for reducing N-losses and the necessity of
      standardising the maturity indices due to their great importance amongst compost
      quality criteria.

PMID- 19119003
TI  - Performance of a composite membrane bioreactor treating toluene vapors: inocula
      selection, reactor performance and behavior under transient conditions.
AB  - In this study, a membrane biofilm reactor performance for toluene as a model
      pollutant is presented. A composite membrane consisting of a porous
      polyacrylonitrile (PAN) support layer coated with a very thin (0.3 microm) dense
      polydimethylsiloxane (PDMS) top layer was used. Batch experiments were performed
      to select an appropriate inocula (slaughterhouse wastewater treatment sludge with
      a specific toluene consumption rate of 118+/-23 microg g(-1) VSS L(-1)) among the
      three available sources of inoculums. The maximum elimination capacity gas-side
      reactor volume based (EC)v and membrane based (EC)(m, max) obtained were 609 g m(
      3) h(-1) and 1.2 g m(-2) h(-1) respectively, which is much higher than other
      membrane bioreactors. Further experiments involved the study of the membrane
      biofilm reactor flexibility when operational parameters as temperature, loading
      rate etc. were modified. In all cases, the membrane biofilm reactor showed a
      rapid adaptation and new steady-states were obtained within hours. Overall, the
      results illustrate that membrane bioreactors can potentially be a good option for
      treatment of air pollutants such as toluene.

PMID- 19119004
TI  - A multi-criteria ranking of different technologies for the anaerobic digestion
      for energy recovery of the organic fraction of municipal solid wastes.
AB  - This paper describes a conceptual framework and methodological tool developed for
      the evaluation of different anaerobic digestion technologies suitable for
      treating the organic fraction of municipal solid waste, by introducing the multi
      criteria decision support method Electre III and demonstrating its related
      applicability via a test application. Several anaerobic digestion technologies
      have been proposed over the last years; when compared to biogas recovery from
      landfills, their advantage is the stability in biogas production and the
      stabilization of waste prior to final disposal. Anaerobic digestion technologies
      also show great adaptability to a broad spectrum of different input material
      beside the organic fraction of municipal solid waste (e.g. agricultural and
      animal wastes, sewage sludge) and can also be used in remote and isolated
      communities, either stand-alone or in conjunction to other renewable energy
      sources. Main driver for this work was the preliminary screening of such methods
      for potential application in Hellenic islands in the municipal solid waste
      management sector. Anaerobic digestion technologies follow different approaches
      to the anaerobic digestion process and also can include production of compost. In
      the presented multi-criteria analysis exercise, Electre III is implemented for
      comparing and ranking 5 selected alternative anaerobic digestion technologies.
      The results of a performed sensitivity analysis are then discussed. In
      conclusion, the performed multi-criteria approach was found to be a practical and
      feasible method for the integrated assessment and ranking of anaerobic digestion
      technologies by also considering different viewpoints and other uncertainties of
      the decision-making process.

PMID- 19119005
TI  - Sulfite pretreatment (SPORL) for robust enzymatic saccharification of spruce and
      red pine.
AB  - This study established a novel process using sulfite pretreatment to overcome
      recalcitrance of lignocellulose (SPORL) for robust and efficient bioconversion of
      softwoods. The process consists of sulfite treatment of wood chips under acidic
      conditions followed by mechanical size reduction using disk refining. The results
      indicated that after the SPORL pretreatment of spruce chips with 8-10% bisulfite
      and 1.8-3.7% sulfuric acid on oven dry (od) wood at 180 degrees C for 30 min,
      more than 90% cellulose conversion of substrate was achieved with enzyme loading
      of about 14.6 FPU cellulase plus 22.5 CBU beta-glucosidase per gram of od
      substrate after 48 h hydrolysis. Glucose yield from enzymatic hydrolysis of the
      substrate per 100 g of untreated od spruce wood (glucan content 43%) was about 37
      g (excluding the dissolved glucose during pretreatment). Hemicellulose removal
      was found to be as critical as lignin sulfonation for cellulose conversion in the
      SPORL process. Pretreatment altered the wood chips, which reduced electric energy
      consumption for size reduction to about 19 Wh/kg od untreated wood, or about 19 g
      glucose/Wh electricity. Furthermore, the SPORL produced low amounts of
      fermentation inhibitors, hydroxymethyl furfural (HMF) and furfural, of about 5
      and 1 mg/g of untreated od wood, respectively. In addition, similar results were
      achieved when the SPORL was applied to red pine. By building on the mature
      sulfite pulping and disk refining technologies already practiced in the pulp and
      paper industry, the SPORL has very few technological barriers and risks for
      commercialization.

PMID- 19119006
TI  - Benzyldihydroxyoctenone, a novel anticancer agent, induces apoptosis via
      mitochondrial-mediated pathway in androgen-sensitive LNCaP prostate cancer cells.
AB  - This study was aimed to evaluate detailed mechanisms on the apoptotic induction
      of benzyldihydroxyoctenone, a novel compound isolated from Streptomyces sp.
      KACC91015, in androgen-sensitive LNCaP prostate cancer cells.
      Benzyldihydroxyoctenone, designated as F3-2-5 in the current study, caused
      accumulation of apoptotic sub-G(1) phase in the flow cytometric analysis using
      propidium iodide staining. Moreover, the typical apoptotic DNA fragmentation of
      the LNCaP cells treated with 30 microM of F3-2-5 was confirmed using the TUNEL
      assay. This apoptotic induction of F3-2-5 in the LNCaP cells was associated with
      the cytochrome c release from mitochondria to cytosol, and the activation of
      procaspase-8, -9, and -3, as well as the specific proteolytic cleavage of
      poly(ADP-ribose) polymerase (PARP). In addition, F3-2-5 treatment caused the down
      regulation of the antiapoptotic protein, such as Bcl-2 and Bcl-X(L), but the
      proapoptotic protein, such as Bax, was not influenced. To investigate whether
      apoptotic induction by F3-2-5 is also due to the down-regulation of androgen
      receptor (AR), Western blot analysis and quantitative RT-PCR were conducted in F3
      2-5-treated LNCaP prostate cancer cells. We found that F3-2-5 significantly
      inhibited the expression levels of AR and prostate-specific antigen (PSA)
      proteins in a time-dependent manner, as well as F3-2-5 abrogated the up
      regulation of AR and PSA genes with and without DHT. Therefore, F3-2-5 has been
      shown to be an androgen antagonist, suggesting that F3-2-5 could be a potent
      agent for the treatment of both androgen-dependent and hormone-refractory
      prostate cancer.

PMID- 19119007
TI  - Novel imidazole-based histamine H3 antagonists.
AB  - A novel series of imidazole containing histamine H(3) receptor ligands were
      investigated and found to be potent functional antagonists. After improving the
      stability of these molecules towards liver microsomes, these compounds were found
      to have no appreciable affinity for CYP P450s. Subsequent in vivo experiments
      showed significant brain uptake of (4-chloro-phenyl)-[2-(1-isopropyl-piperidin-4
      ylmethoxy)-3-methyl-3H-imidazol-4-yl]-methanone 22.

PMID- 19119008
TI  - Probing UDP-galactopyranose mutase binding pocket: a dramatic effect on
      substitution of the 6-position of UDP-galactofuranose.
AB  - UDP-galactopyranose mutase (UGM) catalyzes the isomerization of UDP
      galactopyranose (UDP-Galp) into UDP-galactofuranose (UDP-Galf), an essential step
      of the mycobacterial cell wall biosynthesis. UDP-(6-deoxy-6-fluoro)-D
      galactofuranose 1 was tested as substrate of UGM. Turnover could be observed by
      HPLC. The k(cat) (7.4s(-1)) and the K(m) (24 mM) of 1 were thus measured and
      compared with those of UDP-Galf and other fluorinated analogs. The presence of
      the fluorine atom at the 6-position had a moderate effect on the rate of the
      reaction but a huge one on the interactions between the enzyme and its substrate.
      This result demonstrated that key interactions occur at the vicinity of the 6
      position of UDP-galactose in the Michaelis complex.

PMID- 19119009
TI  - Oxidosqualene cyclase from Saccharomyces cerevisiae, Trypanosoma cruzi,
      Pneumocystis carinii and Arabidopsis thaliana expressed in yeast: a model for the
      development of novel antiparasitic agents.
AB  - A series of 25 compounds, some of which previously were described as inhibitors
      of human liver microsomal oxidosqualene cyclase (OSC), were tested as inhibitors
      of Saccharomyces cerevisiae, Trypanosoma cruzi, Pneumocystis carinii and
      Arabidopsis thaliana OSCs expressed in an OSC-defective strain of S. cerevisiae.
      The screening identified three derivatives particularly promising for the
      development of novel anti-Trypanosoma agents and eight derivatives for the
      development of novel anti-Pneumocystis agents.

PMID- 19119010
TI  - Ants learn geometry and features.
AB  - Rats trained to relocate a particular corner in a rectangular arena
      systematically confound the correct corner and the diametrically opposite one-
      this rotational error demonstrates the use of the geometry of space (i.e., the
      spatial arrangement of the different components of a visual scene). In many
      cases, geometric information is preferentially used over other spatial cues,
      suggesting the presence of a dedicated geometric module located in the
      parahippocampus and processing only geometric information. Since rotational
      errors were first demonstrated in 1986, the use of the geometry of space has
      attracted great interest and now seems to be widespread in vertebrate species,
      including humans. Until now, rotational errors have only been considered in
      vertebrate species. Here, for the first time, rotational errors are demonstrated
      in an insect. Our results, similar to those obtained with vertebrates, can be
      parsimoniously explained by a view-based matching strategy well known in insects,
      thereby challenging the hypothesis of a "geometric module" located in the
      animal's brain. While introducing a new concept of flexibility in the view-based
      matching theory, this study creates a link between two major topics of animal
      navigation: rotational errors in vertebrates and view-based navigation in
      insects.

PMID- 19119011
TI  - Three distinct condensin complexes control C. elegans chromosome dynamics.
AB  - BACKGROUND: Condensin complexes organize chromosome structure and facilitate
      chromosome segregation. Higher eukaryotes have two complexes, condensin I and
      condensin II, each essential for chromosome segregation. The nematode
      Caenorhabditis elegans was considered an exception, because it has a mitotic
      condensin II complex but appeared to lack mitotic condensin I. Instead, its
      condensin I-like complex (here called condensin I(DC)) dampens gene expression
      along hermaphrodite X chromosomes during dosage compensation. RESULTS: Here we
      report the discovery of a third condensin complex, condensin I, in C. elegans. We
      identify new condensin subunits and show that each complex has a conserved five
      subunit composition. Condensin I differs from condensin I(DC) by only a single
      subunit. Yet condensin I binds to autosomes and X chromosomes in both sexes to
      promote chromosome segregation, whereas condensin I(DC) binds specifically to X
      chromosomes in hermaphrodites to regulate transcript levels. Both condensin I and
      II promote chromosome segregation, but associate with different chromosomal
      regions during mitosis and meiosis. Unexpectedly, condensin I also localizes to
      regions of cohesion between meiotic chromosomes before their segregation.
      CONCLUSIONS: We demonstrate that condensin subunits in C. elegans form three
      complexes, one that functions in dosage compensation and two that function in
      mitosis and meiosis. These results highlight how the duplication and divergence
      of condensin subunits during evolution may facilitate their adaptation to
      specialized chromosomal roles and illustrate the versatility of condensins to
      function in both gene regulation and chromosome segregation.

PMID- 19119012
TI  - New N-substituted 9-azabicyclo[3.3.1]nonan-3alpha-yl phenylcarbamate analogs as
      sigma2 receptor ligands: synthesis, in vitro characterization, and evaluation as
      PET imaging and chemosensitization agents.
AB  - A series of N-substituted 9-azabicyclo[3.3.1]nonan-3alpha-yl phenylcarbamate
      analogs were synthesized. Among them, WC-26 and WC-59 were identified as the most
      potent sigma(2) receptor ligands (K(i)=2.58 and 0.82 nM, respectively) with high
      selectivity against sigma(1) (K(i) of sigma(1)/sigma(2) ratio=557 and 2087,
      respectively). [(18)F]WC-59 was radiolabeled via a nucleophilic substitution of a
      mesylate precursor by [(18)F]fluoride, and in vitro direct binding studies of
      [(18)F]WC-59 were conducted using membrane preparations from murine EMT-6 solid
      breast tumors. The results indicate that [(18)F]WC-59 binds specifically to
      sigma(2) receptors in vitro (K(d)= approximately 2 nM). Biodistribution studies
      of [(18)F]WC-59 in EMT-6 tumor-bearing mice indicated that the tracer was a less
      suitable candidate for clinical imaging studies than existing F-18 labeled
      sigma(2) receptor ligands. The ability of WC-26 to enhance the cytotoxic effects
      of the chemotherapy drug, doxorubicin, was evaluated in cell culture using the
      mouse breast tumor EMT-6 and the human tumor MDA-MB435. WC-26 greatly increased
      the ability of doxorubicin to kill these two tumor cell lines in vitro. These
      results indicate that WC-26 is potentially a useful chemosensitizer for the
      treatment of cancer when combined with conventional chemotherapeutics.

PMID- 19119013
TI  - Synthesis and evaluation of rifabutin analogs against Mycobacterium avium and
      H(37)Rv, MDR and NRP Mycobacterium tuberculosis.
AB  - Clinical utility of rifabutin 1 (RBT), a potent antibiotic used in multidrug
      regimens for tuberculosis (TB) as well as for infections caused by Mycobacterium
      avium complex (MAC), has been hampered due to dose-limiting toxicity. RBT analogs
      2-11 were synthesized and evaluated against M. avium 1581 and Mycobacterium
      tuberculosis susceptible and resistant strains in vitro. A selection of
      candidates were also assayed against non-replicating persistent (NRP) M.
      tuberculosis. Subsequent in vivo studies with the best preclinical candidate
      drugs 5 and 8, in a model of progressive pulmonary tuberculosis of Balb/C mice
      infected either with H(37)Rv drug-sensible strain or with multidrug resistant
      (MDR) clinical isolates, resistant to all primary antibiotics including
      rifampicin, were performed. The results disclosed here suggest that 5 and 8 have
      potential for clinical application.

PMID- 19119014
TI  - Carbonic anhydrase inhibitors. Comparison of chlorthalidone, indapamide,
      trichloromethiazide, and furosemide X-ray crystal structures in adducts with
      isozyme II, when several water molecules make the difference.
AB  - Thiazide and high ceiling diuretics were recently shown to inhibit all mammalian
      isoforms of carbonic anhydrase (CA, EC 4.2.1.1) with a very different profile as
      compared to classical inhibitors, such as acetazolamide, methazolamide, and
      ethoxzolamide. Some of these structurally related compounds have a very different
      behavior against the widespread isozyme CA II, with chlorthalidone,
      trichloromethiazide, and furosemide being efficient inhibitors against CA II
      (K(I)s of 65-138 nM), whereas indapamide is a much weaker one (K(I) of 2520 nM).
      Furthermore, some of these diuretics are quite efficient (low nanomolar)
      inhibitors of other isoforms, for example, chlorthalidone against hCA VB, VII,
      IX, and XIII; indapamide against CA VII, IX, XII, and XIII, trichloromethiazide
      against CA VII and IX, and furosemide against CA I and XIV. Examining the four X
      ray crystal structures of their CA II adducts, we observed several (2-3) active
      site water molecules interacting with the chlorthalidone, trichloromethiazide,
      and furosemide scaffolds which may be responsible for this important difference
      of activity. Indeed, indapamide bound to CA II has no interactions with active
      site water molecules. Chlorthalidone bound within the CA II active site is in an
      enolic (lactimic) tautomeric form, with the enolic OH also participating in two
      strong hydrogen bonds with Asn67 and a water molecule. The newly evidenced
      binding modes of these diuretics may be exploited for designing better CA II
      inhibitors as well as compounds with selectivity/affinity for various isoforms
      with medicinal chemistry applications.

PMID- 19119015
TI  - Extended radiation source imaging with a prototype Compton imager.
AB  - This paper reports results from a prototype Compton imager (PCI) which consists
      of three planes of silicon pixel detectors as a scattering detector followed by
      an array of CsI(Tl) crystals as an absorbing detector. The CsI(Tl) array is
      mounted directly behind the silicon detectors. Simple back-projection algorithms
      are not sufficient to resolve extended shapes, but iterative algorithms provide
      the necessary de-convolution. List-mode maximum likelihood expectation
      maximization (LM-MLEM) is an iterative algorithm that reconstructs the most
      probable source distribution for a given data set. LM-MLEM attempts to
      reconstruct an image by finding successive approximations to the true source
      data. Each data set imaged is different, but the number of iterations required
      for convergence is typically 10-30 for the PCI. In this paper, reconstructed
      images of point and extended sources using measured PCI data are presented. Data
      are corroborated using GEANT4 simulations.

PMID- 19119017
TI  - Temporalis myofascial flap in maxillary reconstruction: anatomical study and
      clinical application.
AB  - The authors describe indications and advantages of temporalis myofascial flap in
      the reconstruction of surgical defects after partial maxillectomies. This flap is
      thin and reliable and can be used as an alternative to free flap tissue transfer
      in the reconstruction of partial defects of the upper maxilla. The surgical steps
      to raise the flap are simple, but the dissection must be careful to avoid damages
      to the fronto-temporal branches of the facial nerve on the outer surface, and to
      the feeding vessels on the inner surface of the temporal muscle. In the present
      series no major surgical complications were observed. No injuries to the facial
      nerve branches were reported. Neither total nor partial flap losses were
      experienced. Post-operative aesthetic and functional results were satisfying.
      Temporalis muscle flap can be considered as a first-line reconstructive option
      for limited resection of the upper maxilla with sparing of the orbital floor and
      of the anterior alveolar crest.

PMID- 19119016
TI  - The root application of a purified leonardite humic acid modifies the
      transcriptional regulation of the main physiological root responses to Fe
      deficiency in Fe-sufficient cucumber plants.
AB  - The aim of this study is to investigate the effect of a well-characterized
      purified humic acid (non-measurable concentrations of the main plant hormones
      were detected) on the transcriptional regulation of the principal molecular
      agents involved in iron assimilation. To this end, non-deficient cucumber plants
      were treated with different concentrations of a purified humic acid (PHA) (2, 5,
      100 and 250 mg of organic carbonL(-1)) and harvested 4, 24, 48, 76 and 92 h from
      the onset of the treatment. At harvest times, the mRNA transcript accumulation of
      CsFRO1 encoding for Fe(III) chelate-reductase (EC 1.16.1.7); CsHa1 and CsHa2
      encoding for plasma membrane H+-ATPase (EC 3.6.3.6); and CsIRT1 encoding for
      Fe(II) high-affinity transporter, was quantified by real-time RT-PCR. Meanwhile,
      the respective enzyme activity of the Fe(III) chelate-reductase and plasma
      membrane H+-ATPase was also investigated. The results obtained indicated that PHA
      root treatments affected the regulation of the expression of the studied genes,
      but this effect was transient and differed (up-regulation or down-regulation)
      depending on the genes studied. Thus, principally the higher doses of PHA caused
      a transient increase in the expression of the CsHa2 isoform for 24 and 48 h
      whereas the CsHa1 isoform was unaffected or down-regulated. These effects were
      accompanied by an increase in the plasma membrane H+-ATPase activity for 4, 48
      and 96 h. Likewise, PHA root treatments (principally the higher doses) up
      regulated CsFRO1 and CsIRT1 expression for 48 and 72 h; whereas these genes were
      down-regulated by PHA for 96 h. These effects were associated with an increase in
      the Fe(III) chelate-reductase activity for 72 h. These effects were not
      associated with a significant decrease in the Fe root or leaf concentrations,
      although an eventual effect on the Fe root assimilation pattern cannot be ruled
      out. These results stress the close relationships between the effects of humic
      substances on plant development and iron nutrition. However, further studies are
      needed in order to elucidate if these effects at molecular level are caused by
      mechanisms involving hormone-like actions and/or nutritional factors.

PMID- 19119018
TI  - A submaximal test to assess back muscle capacity: evaluation of construct
      validity.
AB  - A functional endurance test more specific to common occupational tasks is
      proposed for assessing back muscle capacity. The test involves static
      intermittent contractions (8-s work-rest cycles) using a predefined absolute load
      (90 Nm) across subjects. Since the test involved an absolute endurance task, it
      was hypothesized that performance would be influenced by both the strength and
      relative endurance of the subjects, thus demonstrating the construct validity of
      this new test. Fifteen males and 17 females were assessed on three different days
      to allow familiarization and to measure their Strength as well as their absolute
      and relative endurance. Absolute and relative endurance were defined as the time
      to reach exhaustion (Tend(abs) and Tend(rel), respectively) during a fatigue
      protocol including both an absolute (90 Nm) and a relative (40% of individual
      strength) load (extension moment at the L5/S1 joint). Strength and Tend(rel) each
      explained an almost equivalent portion of Tend(abs) (total variance explained:
      61.5%), thus confirming the construct validity of the functional endurance test.
      This new test should better identify the back muscle impairments (weakness,
      fatigability) often observed in chronic low-back-pain patients.

PMID- 19119019
TI  - Subscapularis function after primary tendon to tendon repair in patients after
      replacement arthroplasty of the shoulder.
AB  - HYPOTHESIS: We studied the results of tendon-to-tendon repair of the
      subscapularis during total shoulder arthroplasty (TSA) to compare its clinical
      results relative to more recent studies looking at osteotomy of the lesser
      tuberosity. MATERIALS AND METHODS: This study analyzed the postoperative
      integrity of the subscapularis by a tendon-to-tendon repair in 45 arthroplasties
      in 43 patients. RESULTS: Preoperatively, 23 patients had a negative lift-off
      test; 22 could not perform the test. Postoperatively, 41 patients had a negative
      lift-off test; four could not reach behind themselves to do the test. All 45
      shoulders had a negative belly-press test pre-operatively and post-operatively.
      DISCUSSION: Tendon-to-tendon repair is simpler, quicker, and avoids the
      possibility of an osteotomy nonunion. Tendon-to-tendon repair of the
      subscapularis tenotomy in shoulder arthroplasty remains an option in the presence
      of reasonable quality tendon, utilizing relaxing sutures (partial closure of the
      lateral rotator interval), and limiting early postoperative passive external
      rotation. LEVEL OF EVIDENCE: Level 4; Retrospective case series, no control
      group.

PMID- 19119020
TI  - Transfusion after shoulder arthroplasty: an analysis of rates and risk factors.
AB  - HYPOTHESIS: Advancing age, lower preoperative hemoglobin levels, and more complex
      procedures are risk factors in transfusion requirements following shoulder
      arthroplasty. MATERIALS AND METHODS: We retrospectively reviewed the records of
      196 consecutive shoulder arthroplasties performed by a single surgeon (including
      113 primary noncomplex total shoulder arthroplasties, 27 primary noncomplex
      hemiarthroplasties, 37 revision or complex arthroplasties, and 19 reverse
      shoulder arthroplasties). Logistic regression analysis was used to determine
      which clinical variables were associated with the need for postoperative
      transfusion. RESULTS: The overall transfusion rate was 43% (84/196). The presence
      of preoperative anemia (males <13 g/dl, females <12 g/dl), decreasing
      preoperative hemoglobin levels, female gender, increasing age, and implantation
      of a reverse shoulder arthroplasty were independent risk factors for
      postoperative transfusion. Operative time, estimated blood loss, anesthesia type,
      preoperative use of anticoagulants and body mass index (BMI) were not found to be
      predictive of transfusion. DISCUSSION: Our results corroborate the few existing
      studies regarding the effects of lower preoperative hemoglobin levels on
      transfusion risk following shoulder arthroplasty. In contrast to these studies,
      however, we found increasing age and the implantation of a reverse shoulder
      arthroplasty to be independent predictors for transfusion. CONCLUSION: The
      results of the present study support close postoperative monitoring of older,
      female patients (>65 years), patients with preoperative anemia (males <13 g/dl,
      females <12 g/dl), and those undergoing reverse shoulder replacement. These
      patients should be educated before surgery of the potential need for
      postoperative blood transfusion. LEVEL OF EVIDENCE: Level 4; Retrospective case
      series, no control group.

PMID- 19119021
TI  - Isolated suprascapular nerve injury below the spinoglenoid notch after SLAP
      repair.

PMID- 19119022
TI  - Serious psychological distress and health outcomes for persons with epilepsy in
      poverty.
AB  - Epidemiology literature demonstrates socioeconomic status as an important
      variable for outcomes in persons with epilepsy. However, no previous studies have
      analyzed the association between poverty and epilepsy in the United States. Forty
      one percent (246/604) of persons with a history of epilepsy (PWHE) in the 2005
      California Health Interview Survey (n=43,020) had an annual income <200% Federal
      Poverty Level (FPL), adjusted lifetime prevalence rate 0.5% [98.33% CI 0.4-0.7].
      Four groups are presented in the analyses: (1) those with a history of epilepsy
      <200% FPL, (2) those with a history of epilepsy > or =200% FPL, (3) those not
      reporting a history of epilepsy <200% FPL and (4) those not reporting a history
      of epilepsy > or =200% FPL. PWHE in poverty reported significantly higher amounts
      of serious psychological distress, based on the validated Kessler 6 (K6) scale,
      than both non-epilepsy populations. After adjusting for demographics and other
      comorbid conditions, logistic regression analyses show PWHE in poverty are
      significantly more likely to report fair or poor self-rated health status when
      compared to the PWHE not in poverty and both non-epilepsy populations. PWHE in
      poverty are also more likely to report > or =14 generally unhealthy days and > or
      =14 physically unhealthy days in the past 30 days compared to the PWHE not in
      poverty and both non-epilepsy populations. Psychological well-being needs to be
      incorporated into any comprehensive treatment strategy for managing epilepsy.

PMID- 19119023
TI  - Fatal hepatitis mediated by tumor necrosis factor TNFalpha requires caspase-8 and
      involves the BH3-only proteins Bid and Bim.
AB  - Apoptotic death of hepatocytes, a contributor to many chronic and acute liver
      diseases, can be a consequence of overactivation of the immune system and is
      often mediated by TNFalpha. Injection with lipopolysaccharide (LPS) plus the
      transcriptional inhibitor D(+)-galactosamine (GalN) or mitogenic T cell
      activation causes fatal hepatocyte apoptosis in mice, which is mediated by
      TNFalpha, but the effector mechanisms remain unclear. Our analysis of gene
      targeted mice showed that caspase-8 is essential for hepatocyte killing in both
      settings. Loss of Bid, the proapoptotic BH3-only protein activated by caspase-8
      and essential for Fas ligand-induced hepatocyte killing, resulted only in a minor
      reduction of liver damage. However, combined loss of Bid and another BH3-only
      protein, Bim, activated by c-Jun N-terminal kinase (JNK), protected mice from
      LPS+GalN-induced hepatitis. These observations identify caspase-8 and the BH3
      only proteins Bid and Bim as potential therapeutic targets for treatment of
      inflammatory liver diseases.

PMID- 19119024
TI  - Late developmental plasticity in the T helper 17 lineage.
AB  - Development of T helper (Th) 17 cells requires transforming growth factor (TGF)
      beta and interleukin (IL)-6 and is independent of the Th1 pathway. Although T
      cells that produce interferon (IFN)-gamma are a recognized feature of Th17 cell
      responses, mice deficient for STAT4 and T-bet-two prototypical Th1 transcription
      factors-are protected from autoimmunity associated with Th17 pathogenesis. To
      examine the fate and pathogenic potential of Th17 cells and origin of IFN-gamma
      producing T cells that emerge during Th17 immunity, we developed IL-17F reporter
      mice that identify cells committed to expression of IL-17F and IL-17A. Th17 cells
      required TGF-beta for sustained expression of IL-17F and IL-17A. In the absence
      of TGF-beta, both IL-23 and IL-12 acted to suppress IL-17 and enhance IFN-gamma
      production in a STAT4- and T-bet-dependent manner, albeit with distinct
      efficiencies. These results support a model of late Th17 developmental plasticity
      with implications for autoimmunity and host defense.

PMID- 19119026
TI  - Induction of autoantibody-mediated spontaneous arthritis critically depends on
      follicular dendritic cells.
AB  - Follicular dendritic cells (FDCs) are important for the induction of protective T
      cell-dependent humoral responses, but their contribution to autoimmunity remains
      elusive. Here, gene-targeted interruption of FDC development was combined with
      the K/BxN mouse model of arthritis. We found that FDCs were essential for
      autoantibody production through two distinct but cooperative functions. In a T
      cell-independent fashion, FDCs loaded with autoantigen-containing immune
      complexes supported germinal center (GC) B cell development. Additionally, the
      integrity of FDC networks was required for the recruitment of arthritogenic
      follicular helper T cells, a process that drove T-B cell interactions and
      productive GC reactivity. Importantly, pharmacological interference in the
      maintenance of FDCs ameliorated disease development, suggesting the FDC as a
      potential target for dampening autoimmunity.

PMID- 19119025
TI  - Insights into MHC class I peptide loading from the structure of the tapasin-ERp57
      thiol oxidoreductase heterodimer.
AB  - Tapasin is a glycoprotein critical for loading major histocompatibility complex
      (MHC) class I molecules with high-affinity peptides. It functions within the
      multimeric peptide-loading complex (PLC) as a disulfide-linked, stable
      heterodimer with the thiol oxidoreductase ERp57, and this covalent interaction is
      required to support optimal PLC activity. Here, we present the 2.6 A resolution
      structure of the tapasin-ERp57 core of the PLC. The structure revealed that
      tapasin interacts with both ERp57 catalytic domains, accounting for the stability
      of the heterodimer, and provided an example of a protein disulfide isomerase
      family member interacting with substrate. Mutational analysis identified a
      conserved surface on tapasin that interacted with MHC class I molecules and was
      critical for peptide loading and editing functions of the tapasin-ERp57
      heterodimer. By combining the tapasin-ERp57 structure with those of other defined
      PLC components, we present a molecular model that illuminates the processes
      involved in MHC class I peptide loading.

PMID- 19119027
TI  - Implementation of endovenous laser ablation for varicose veins in a large
      community hospital: the first 400 procedures.
AB  - Endovenous laser ablation (ELA) has become a standard treatment of the
      incompetent great saphenous vein (GSV). Our prospective audit examines the
      implementation of this new method in a large community hospital with special
      attention to obstacles, technical results, pain scores, failures and our learning
      curve. METHODS: Three hundred and twenty-three patients (403 limbs) with
      incompetence of the GSV underwent ELA. Patients were assessed by clinical
      examination and venous duplex ultrasound was performed 6 weeks after operation.
      Visual analog scale (VAS) pain scores of the first postoperative week were
      recorded. Operative time and success rate were analysed. RESULTS: After 6 weeks,
      301 (74.7%) treated legs were examined by duplex ultrasound imaging. Successful
      complete occlusion was present in 282 (93.7%) GSVs. Partial occlusion was present
      in 12 (4.0%) GSVs. In seven (2.3%) limbs the GSV was not occluded. The maximum
      mean VAS pain score was noted on the 5th postoperative day. From the start of
      this series, the operation time decreased rapidly for each surgeon, stabilising
      after 15 limbs. CONCLUSION: ELA of the incompetent GSV is effective and safe. ELA
      is simple to perform, well accepted by patients and relatively atraumatic. In our
      opinion, ELA can be easily implemented in surgical practice.

PMID- 19119028
TI  - Expansion of small-diameter abdominal aortic aneurysms is not reflected by the
      release of inflammatory mediators IL-6, MMP-9 and CRP in plasma.
AB  - OBJECTIVES: The aim of this study was to evaluate a possible correlation between
      plasma levels of interleukin-6 (IL-6), metalloproteinase-9 (MMP-9) and C-reactive
      protein (CRP) and the expansion of small abdominal aortic aneurysms (AAAs).
      DESIGN: Patients were selected from a prospective randomised clinical trial and
      categorised in two groups, in which one group received active treatment
      (azithromycin) and the other received placebo. No statistical difference in the
      expansion rate of AAAs between the groups was found and the two groups were
      considered as one cohort in the present study. MATERIAL AND METHODS: In this
      study, 213 patients with AAAs between 35 and 49 mm were followed-up with
      ultrasound examination every 6th month. Blood samples were taken on two occasions
      (6 months apart). IL-6 and MMP-9 were analysed on one occasion using Quantikine
      analysing kits (R&D Systems, Inc., USA). CRP was analysed using sensitive-CRP
      method. RESULTS: Levels of IL-6, MMP-9 and CRP did not correlate with AAA
      expansion. Neither was there any correlation between statin medication and
      changes in MMP-9 levels over the 6-month period. Patients on statins had a lower
      expansion rate than those not taking statins: 0.16 versus 0.25 cm per year.
      CONCLUSION: No correlation was found between levels of circulating IL-6, MMP-9,
      CRP and the expansion of small-diameter AAAs, indicating no clinical use of these
      markers in AAA surveillance.

PMID- 19119029
TI  - Applications of transcranial magnetic stimulation in sleep medicine.
AB  - Transcranial magnetic stimulation (TMS) is a new method, developed nearly 20
      years ago, that allows the study of cortical excitability. The whole brain
      undergoes profound changes in sleep. Motor evoked potentials (MEPs) have been
      used to trace the effects of sleep on cortical excitability and to the
      corticomotoneuron connections. Although in the past some technical aspects
      limited the application of TMS in sleep, recently we observed a new explosion of
      interest in this field. The main body of data was gathered on sleep physiology,
      but its diseases or syndromes were also studied in detail. Many single and paired
      pulse-TMS variables were applied. Moreover, TMS variables were investigated as a
      potential tool for the diagnosis or the differential diagnosis of sleep
      disorders. In the recent years, the advent of repetitive TMS offered some
      therapeutic perspectives, which are under current investigation in few of these
      disorders. Combining repetitive TMS with electroencephalogram (EEG) represents a
      new and probably useful approach to sleep. Among the main entities classified in
      the sleep disease group, the following were subject to TMS studies: obstructive
      sleep apnoea syndrome (OSAS), propriospinal myoclonus, restless legs syndrome
      (RLS) with periodic limb movement and narcolepsy. For each of these, we examine
      the applications of TMS separately.

PMID- 19119030
TI  - Quantitative real-time PCR detection of insulin signalling-related genes in
      pancreatic islets isolated from healthy cats.
AB  - The cat has recently been proposed as a valuable model for type 2 diabetes
      mellitus (T2DM), because feline diabetes shares several similarities with the
      disease in humans. Impaired beta-cell function, decreased beta-cell mass, insulin
      resistance that is often related to obesity, and pancreatic amyloid deposition,
      are among these common features. In this study, and to further develop the cat as
      a model of T2DM, feline pancreatic islets were isolated and real-time PCR
      quantification of mRNA transcripts of genes central to beta-cell function and
      survival established. In particular, mRNA quantification systems were determined
      for insulin, the insulin enhancer pancreatic duodenal homeobox-1 (PDX-1), the
      insulin suppressor CCAAT/enhancer binding protein-beta (C/EBPbeta), glucose
      transporter isoform 2 (GLUT2), Fas receptor, the caspase-8 inhibitor FLIP (FLICE
      [caspase-8]-inhibitory protein) and two chemokines, interleukin (IL)-8 and
      monocyte chemoattractant protein-1 (MCP-1). Pancreatic islets were isolated by
      collagenase digestion from healthy cat donors. Partial feline mRNA sequences were
      determined for PDX-1, C/EBPbeta, GLUT2 and FLIP using primers identified from
      conserved regions of human, dog and rat mRNA. These novel and the previously
      available sequences (insulin, Fas receptor, IL-8 and MCP-1) were used to design
      feline-specific primers suitable for real-time PCR in isolated pancreatic islets.
      The adopted protocol of collagenase digestion yielded pancreatic islets that were
      frequently surrounded by acinar cells. Quantification of mRNA transcripts was
      simple and reproducible in healthy cats. Characterisation of genes related to
      insulin signalling in cats will prove useful to better understand the
      pathogenesis of feline diabetes and possibly of human T2DM.

PMID- 19119031
TI  - Categories of congruence between inpatient self-reported pain and nurses
      evaluation.
AB  - OBJECTIVE: To enhance the awareness that biased pain estimation may undermine its
      treatment, we sought to determine the congruence categories (CCs) between
      inpatient self-reported pain (PSRP) and nurse pain-evaluation (NEP) and to look
      for associations between CCs and inpatient and situational moderators. DESIGN: A
      point cross-sectional survey. SUBJECTS: The inpatient population [(n=869), > or =
      6 years old and hospitalised for at least 24h] and n=115 nurses of the University
      of Bologna's teaching hospital, Italy. MEASURES: Using numerical rating scale,
      inpatients self-reported their pain while nurses indirectly rated these patients'
      pain using information acquired during their professional activity prior to the
      study and by reviewing patients' medical charts. OUTCOME MEASURES: Congruence
      moderator data were: gender, age, marital status, clinical area and length of
      hospital stay. The study was set to assess: PSRP-NEP mean of absolute difference
      (MAD), agreement and correlation; and to analyse the CCs dependence upon the PSRP
      and the congruence moderator variables. RESULTS: PSRP-NEP agreement and
      correlation were mild and moderate, respectively, while their MAD=2.0 (95% CI 1.8
      2.2). Congruence was found in 50% of the cases. Under-estimation (21%) was
      directly proportional to the PSRP severity, while congruence and over-estimation
      (29%) were inversely proportional to it. The 'PSRP effect' on the CCs detected
      was further modulated by the moderators studied. CONCLUSIONS: PSRP-NEP congruence
      was limited while CCs were associated with PSRP, inpatient and situational
      moderators. Further prospective studies are needed to verify generalization and
      whether the studied moderators operate through patient stereotyping mechanisms.
      Awareness of the influence of such mechanisms on pain evaluation may ameliorate
      pain assessment.

PMID- 19119032
TI  - Systemic administration of lidocaine suppresses the excitability of rat cervical
      dorsal horn neurons and tooth-pulp-evoked jaw-opening reflex.
AB  - Although systemic lidocaine has been demonstrated to have analgesic actions in
      neuropathic pain conditions, the effect of intravenous lidocaine on trigeminal
      pain has not been elucidated. The aim of the present study is to investigate the
      effect of intravenous lidocaine administration on the excitability of the upper
      cervical dorsal horn (C1) neuron having convergent inputs from both tooth-pulp
      (TP) and facial skin as well as nociceptive jaw-opening reflex (JOR). After
      electrical stimulation of TP, extracellular single-unit recordings from 19 C1
      neurons and the digastric muscle electromyogram (dEMG) were made in pentobarbital
      anesthetized rats. These neurons also responded to non-noxious and noxious
      mechanical stimulation (touch and pinch) of facial skin, and every neuron was
      considered to be a wide dynamic range (WDR) neuron. The TP-evoked C1 neuronal and
      dEMG activities were dose-dependently inhibited by systematic administration of
      lidocaine (1-2 mg/kg, i.v.). After intravenous injection of lidocaine, the unit
      discharges induced by both touch and pinch stimuli were inhibited, and the size
      of the receptive field for pinch was also significantly decreased. The mean
      spontaneous discharge frequencies were significantly inhibited by the application
      of lidocaine. These changes were reversed within -20 min. These results suggest
      that in the absence of neuropathic pain intravenous lidocaine injection
      suppresses the trigeminal nociceptive reflex as well as the excitability of C1
      neurons having convergent inputs from TP and somatic afferents. Systemic
      lidocaine administration, therefore, may contribute to the alleviation of
      trigeminal-referred pain associated with tooth pain.

PMID- 19119033
TI  - Goal frustration, coping and well-being in the context of adolescent headache: a
      self-regulation approach.
AB  - The aim of this study was to investigate the relationships between goal
      frustration, coping and well-being in the context of adolescent headache.
      Firstly, we investigated whether adolescents with weekly, monthly or no headache
      complaints differed with regard to the importance assigned to their personal
      goals, experience of goal frustration, coping with goal frustration and well
      being. Secondly, the extent to which goal and coping factors contributed to well
      being and whether this relationship differed according to the frequency of
      headache complaints was examined. For this purpose, 1202 adolescents aged 12-18
      completed self-report questionnaires in schools. Adolescents were divided into
      three groups based on their experience of headache: no headache reported (38%);
      monthly headache (40%); weekly headache (18%). Results show that these groups did
      not differ with respect to the importance they attach to goals. They did,
      however, differ according to experience of goal frustration, use of strategies to
      cope with goal frustration and well-being, although effect sizes were small.
      After controlling for individual and headache characteristics, frustration of
      self acceptance and health goals, and the use of self blame, rumination and other
      blame were consistently related to lower well-being. Moreover, interactions with
      headache group indicated that for adolescents with weekly headache, greater
      frustration of school and self acceptance goals and a lower importance assigned
      to health goals was more detrimental to well-being than for those with no
      headache complaints. We conclude that frustration to goal pursuit and strategies
      for coping with this frustration are important factors in adolescent well-being
      and may offer important targets for intervention.

PMID- 19119034
TI  - Optimal control in NMR spectroscopy: numerical implementation in SIMPSON.
AB  - We present the implementation of optimal control into the open source simulation
      package SIMPSON for development and optimization of nuclear magnetic resonance
      experiments for a wide range of applications, including liquid- and solid-state
      NMR, magnetic resonance imaging, quantum computation, and combinations between
      NMR and other spectroscopies. Optimal control enables efficient optimization of
      NMR experiments in terms of amplitudes, phases, offsets etc. for hundreds-to
      thousands of pulses to fully exploit the experimentally available high degree of
      freedom in pulse sequences to combat variations/limitations in experimental or
      spin system parameters or design experiments with specific properties typically
      not covered as easily by standard design procedures. This facilitates
      straightforward optimization of experiments under consideration of rf and static
      field inhomogeneities, limitations in available or desired rf field strengths
      (e.g., for reduction of sample heating), spread in resonance offsets or coupling
      parameters, variations in spin systems etc. to meet the actual experimental
      conditions as close as possible. The paper provides a brief account on the
      relevant theory and in particular the computational interface relevant for
      optimization of state-to-state transfer (on the density operator level) and the
      effective Hamiltonian on the level of propagators along with several
      representative examples within liquid- and solid-state NMR spectroscopy.

PMID- 19119035
TI  - Normograde, minimally invasive technique for oesophagostomy in cats.
AB  - A percutaneous technique to place oesophageal feeding tubes in cats is described.
      Nineteen traumatised cats underwent different surgical procedures for facial
      and/or oral trauma and subsequent oesophagostomy. The tube placement was easy to
      perform, requiring a 14G over-the-needle vascular catheter, a curved forceps and
      a 1.2mm feeding tube. During insertion, the tube was directed aborally
      (normograde direction) to its definitive position in a one-step procedure. The
      tube was removed when the patient started to eat voluntarily. A major limit of
      this technique was represented by the small diameter of the feeding tube,
      requiring the use of a liquid diet. However, considering the absence of
      complications, the rapidity of the procedure and its cost efficacy, it was
      considered as an effective alternative to more complicated and invasive
      techniques, in particular if a short period of starvation is predictable.

PMID- 19119036
TI  - Mycobacterium neoaurum infection in a patient with renal failure.
AB  - Mycobacterium neoaurum, a member of the Mycobacterium parafortuitum complex, has
      only rarely been reported as a pathogen of human infections. We report a case of
      catheter-related bloodstream infection (CRBSI) due to M. neoaurum in a patient on
      hemodialysis. The isolate was identified by conventional methods as well as by
      16S rRNA gene analysis. The patient was successfully treated with intravenous
      antibiotics (meropenem and amikacin) for three weeks and the catheter was
      removed. M. neoaurum should be considered as a possible cause of CRBSI in
      patients with renal failure. Combination antimicrobial therapy and catheter
      removal can lead to a favorable clinical outcome.

PMID- 19119037
TI  - Re-emergence of tularemia in Turkey.
AB  - Four tularemia epidemics were reported from three different regions of Turkey
      between 1936 and 1953. After a long interval, a new tularemia epidemic was
      reported from the area around Bursa in the northwestern part of Turkey in 1988.
      Following this first epidemic in Bursa, small epidemics occurred in areas around
      Bursa between 1988 and 2002. Other tularemia epidemics in different regions of
      Turkey were reported between 1988 and 2005. Almost all of the cases involved the
      oropharyngeal form of the disease. However, ulceroglandular and oculoglandular
      forms were detected in the Bursa epidemics; all of the ulceroglandular cases had
      dermatitis on their hands. To date, 1300 cases have been serologically confirmed.
      We reviewed one of the biggest tularemia epidemics in Europe.

PMID- 19119038
TI  - Improved diagnosis of tuberculosis in HIV-positive patients using RD1-encoded
      antigen CFP-10.
AB  - OBJECTIVE: The present study was aimed at determining the serodiagnostic
      potential of 38-kDa (Rv0934, Mycobacterium tuberculosis complex-specific antigen)
      and CFP-10 (Rv3874, RD1 antigen) antigens among HIV-positive and HIV-negative
      patients with pulmonary TB. METHODS: The diagnostic potential of native 38-kDa
      (n38-kDa) and recombinant CFP-10 (rCFP-10) antigens was ascertained in terms of
      sensitivity and specificity using an indirect ELISA. The study included 508 HIV
      seronegative TB patients (TB), 54 HIV-seropositive TB patients (HIV-TB), 30 HIV
      positive patients without TB (HIV), and 256 controls. RESULTS: In HIV-TB, the
      sensitivities for individual antigens ranged from 14.8% to 31.5% and the
      specificity was >98% for IgG. When IgA results were added to IgG, the sensitivity
      increased to 25.9% for 38-kDa and 57.4% for CFP-10; specificity changed to 97.5%
      for 38-kDa and 98.1% for CFP-10. The combined results of both the antigens gave
      59.3% sensitivity and 95.6% specificity. In TB, the sensitivity was 82.8% when
      the antigen results were combined. None of the HIV-infected controls showed
      positivity for IgG to either of the two antigens. CONCLUSION: Use of CFP-10
      enhances the sensitivity of 38-kDa, and therefore the 38-kDa and CFP-10 antigen
      combination can be a diagnostic marker in HIV-TB.

PMID- 19119039
TI  - Splenic tuberculosis: a case report.
AB  - Splenic tuberculosis is an unusual clinical phenomenon, especially in
      immunocompetent hosts. It often demonstrates diagnostic complexity, which makes
      the identification of the agent difficult. We encountered the case of a middle
      aged immunocompetent male who claimed to be suffering from pain in the left
      hypochondriac region without any indication of cough, hemoptysis, weight loss or
      fever. When physically examined, he had splenomegaly without any other clinical
      findings. This was further confirmed by imaging. A splenectomy was performed, and
      samples were taken for histopathological examination and microbiological
      analysis. Gross examination of the specimen showed multiple nodules coalescing to
      form a large yellowish-white mass of solid consistency. Histopathological
      examination showed large areas of caseation surrounded by multiple granulomas of
      epitheloid cells and Langhan's type giant cells throughout the splenic pulp. PCR
      verified the diagnosis of Mycobacterium tuberculosis infection. No primary focus
      of infection was detected in the lungs or any other organs.

PMID- 19119040
TI  - [Phyllodes tumors of the breast: analysis of 53 patients].
AB  - PURPOSE: Phyllode tumors of the breast are fibroepithelial tumors similar to
      fibroadenomas but with a predominant conjunctive tissue component. These are
      composed of a connective tissue stroma and epithelial elements. They are rare
      with an incidence of 0.3-0.9% of all breast neoplasms. The present study
      demonstrates the recent experiences in diagnosis, therapeutical management and
      clinical follow-up of this disease. PATIENTS AND METHODS: This is a retrospective
      study of the experience of the Institut National d'Oncologie (INO, Rabat) from
      1998 to 2006. RESULTS: We included 53 patients. Median age was 37.2 years (15
      67), tumor size was 1-30cm (median 10.25cm). The histological diagnosis was based
      on the biopsy in (7.8%) cases and extemporany in 22% cases, distant metastasis
      occurred in two patients; the treatment consisted of a surgery. The median follow
      up was three years. Local recurrence occurred in ten patients. Distant metastasis
      occurred in two patients and five patients have died. CONCLUSION: The
      confrontation of our results to the data of the international literature shows
      that the diagnosis of the phyllodes tumours is histological. The basis of the
      treatment is surgery. The adjuvant radiotherapy is very important in patients at
      high risk for local recurrence; chemotherapy has a badly defined place. The
      prognostic is based on the histological characters of the tissue conjunctive
      component of these tumours.

PMID- 19119041
TI  - [Radiosurgery of cerebral arteriovenous malformations: a prescription algorithm].
AB  - PURPOSE: To study prognostic factors of obliteration and risk factors of brain
      radiation necrosis in order to propose an algorithm for radiosurgery prescription
      for cerebral arteriovenous malformations (cAVM). MATERIAL AND METHODS: One
      hundred and seventy-nine patients were analysed. Radiosurgery delivered 6 or 10
      MV X-rays by arc therapy in 84% of cases, or by fixed field in 16% of cases using
      two different micro-multileaf collimators (micro-MLC). Follow-up consisted of
      screening radiation necrosis by MRI every 6 months, and assessing local control
      by arteriography every 2 years. Obliteration was defined as at least 95%
      reduction of cAVM volume. Cox proportional hazard model was used to evaluate the
      local control and the appearance of radiation necrosis over time. RESULTS: Local
      control rate was 82.7% with the mean follow-up of 3.1 years (0.5-11). Significant
      prognostic factors were: simple nidus (RR=2.8, p<0.0001), number of embolizations
      before radiosurgery below 4 (RR=2.9, p<0.0001), prescribed dose to the periphery
      of at least 18 Gy (RR=2, p=0.0002), nidus volume below8cm(3) (RR=1.9, p=0.0002),
      and number of table positions below six (RR=1.4, p=0.05). Radiation necrosis rate
      was 11.2% with a mean time to onset of 18 months. Significant predictive factors
      were: fixed field versus arc therapy (according to MLC RR=9.1, p<0.0001, and
      RR=15.1, p=0.01), age below 30 years (RR=2.5, p=0.04), depth of cAVM greater than
      or equal to 7 cm (RR=7.6, p=0.008), and volume of brain tissue covered by the 12
      Gy isodose (V12 Gy) of at least 11 cm(3) (RR=7.8, p=0.05). CONCLUSION: A
      radiosurgery prescription algorithm taking into account the prescribed dose to
      the periphery (> or = 18 Gy) and reduction of V12 Gy was elaborated from these
      data.

PMID- 19119042
TI  - Reliability of a modified Modic classification of bone marrow changes in lumbar
      spine MRI.
AB  - OBJECTIVE: The purpose of this study was to determine the intra- and
      interobserver reliability of a modified Modic classification for bone marrow
      changes seen on lumbar spine magnetic resonance imaging (MRI), taking into
      consideration mixed signals. METHODS: Lumbar MRI scans from 94 patients with low
      back pain were assessed independently by 2 spine specialists (senior [senior1],
      junior) and a radiologist (senior2). One reviewer (senior1) assessed the MR
      images twice at a three-week interval for evaluation of intraobserver
      reliability. Senior2 and junior reviewers assessed the MR images once. Pure edema
      endplate signal changes were classified as Modic type I, and pure fatty endplate
      changes as Modic type II. A mixture of types I and II but predominantly edema
      signal changes was classified as Modic I-2 and a mixture of types I and II but
      predominantly fatty changes was classified as Modic II-1. RESULTS: The
      intraobserver agreement was excellent (weighted kappa 0.85). The interobserver
      agreement was moderate to substantial (weighted kappa range 0.56-0.74).
      Interobserver reliability depended on the experience of the observer, thus
      highlighting the importance of a learning curve. CONCLUSION: This study shows
      that the modified Modic classification is reliable and easy to apply for
      observers with different clinical experience. The inclusion of mixed marrow
      changes in the modified classification may have clinical and therapeutic
      implications.

PMID- 19119043
TI  - Erdheim-Chester disease with predominant mesenteric localization: lack of
      efficacy of interferon alpha.

PMID- 19119044
TI  - Clinical significance of MEFV mutations in ankylosing spondylitis.
AB  - OBJECTIVE: The aim of the present study was to investigate the prevalence of MEFV
      gene mutations in patients with ankylosing spondylitis (AS) and to assess the
      clinical significance of the MEFV gene mutations in AS. METHODS: Eighty AS
      patients and 85 healthy controls were examined for 12 common MEFV mutations via
      strip-assay technique. Bath ankylosing spondylitis disease activity index
      (BASDAI), bath ankylosing spondylitis functional index (BASFI), visual analogue
      scale (VAS) for pain, erythrocyte sedimentation rate (ESR), C-reactive protein
      (CRP), Schober test, chest expansion measurements, hip involvement, ocular
      involvement, articular pain, and presence of syndesmophytes were used to assess
      the disease severity in patients. RESULTS: Twenty-four of the AS patients (30%)
      and 17 of the healthy controls (20%) were found to carry a single MEFV mutation.
      There was no significant difference between the AS patients and controls in terms
      of MEFV gene mutation frequency (p = 0.13, OR: 1.71, 95% CI: 0.83-3.50). When the
      patients were divided into two groups as MEFV mutation carriers and noncarriers,
      there was significant difference between the groups regarding BASFI and BASDAI
      whereas there was no significant difference in VAS score for pain. No association
      was found with the clinical findings and MEFV mutation except hip involvement.
      While there was no significant difference in CRP levels, individuals with MEFV
      mutation had a higher ESR than the noncarriers. CONCLUSION: MEFV gene mutation
      carriage rate was not found to be significantly higher in AS patients when
      compared with healthy controls. However having an MEFV mutation seems to
      aggravate the disease course in AS.

PMID- 19119045
TI  - [The false equivalent Galeazzi in children].
AB  - We report the case of a false Galeazzi equivalent in children. This injury is
      characterised by an epiphyseal detachment of the distal extremity of the ulna
      rather than a distal radio-ulnar dislocation. A 16-year-old patient was injured
      in a fall from a bike. Radiographs showed a fracture of the radial shaft with
      anterior angulation, together with a type II Salter-Harris epiphyseal injury at
      the level of the distal ulna. We were unable to perform a closed reduction under
      general anesthesia due to interposition of periosteum at the fracture site. Thus
      surgical management was the only option, which consisted of removing the
      offending periosteum and performing osteosynthesis of the radial shaft fracture
      with a plate, and the epiphyseal detachment with pins. After 10 months, we noted
      no bone growth disturbance, or any reduced mobility of the wrist. We will
      continue the follow-up to monitor bone growth disturbance of the distal extremity
      of the ulna.

PMID- 19119046
TI  - [Necessary processes for gynaecological practice setting-up including surgery and
      no obstetrics].

PMID- 19119047
TI  - [Eclampsia: retrospective study about 16 cases].
AB  - OBJECTIVE: To determine the etiologic factors, circumstances of diagnosis,
      obstetrical management and complications of eclampsia and to value the maternal
      and perinatal outcomes. PATIENTS AND METHODS: We conducted a retrospective
      descriptive study, from January 1996 to December 2006 in a maternity type IIB.
      RESULTS: Sixteen cases of eclampsia were studied. The prevalence of eclampsia
      over the study period was 8.1 per 10,000 births, without annual change in the
      incidence. The mean age of the patients was 27.8+/-6.7 years. The major risk
      factor was the primipaternity (87.5%). The eclampsia occurred in ante-, peri- and
      post-partum in 56, 6 and 38% of the cases, respectively. In cases of eclampsia,
      75% of the patients had elevated blood pressure, 93% presented headache, but 62%
      presented with an atypical form with less than three functional symptoms
      (headache, visual trouble, hyperreflexia). Various treatments had been started:
      antihypertensive treatment (75%), antiepileptic treatment (69%) and magnesium
      sulphate (94%). Eleven patients had developed complications, mainly HELLP
      syndrome (10 patients). No maternal death was noted. The mean birth weight was
      2366+/-818 g, 43.8% of children had birth weight less than the 10th percentile,
      and 87.5% of children were girls. One fetal and one perinatal death at day 19 had
      been noted. DISCUSSION AND CONCLUSION: Nowadays, the physiopathology of eclampsia
      remains misunderstood. It is difficult to establish risk factors, the
      primipaternity being certainly one of these. Eclampsia may occur in an atypical
      and unforeseeable form in well followed patients, without risk factor. The
      diagnosis should be done quickly for an adapted treatment and obstetrical
      management.

PMID- 19119048
TI  - [Juvenile granulosa-cell tumor: clinical and molecular expression].
AB  - Ovarian sex cord-stromal tumors are rare tumors that originate from the
      nongerminal cells of ovary. Two decades ago, the identification of juvenile
      granulosa-cell tumors (GCT), as a specific entity inside this group, allowed a
      better treatment of these tumors in children. However, little data have been
      reported on the natural course of the disease and reliable prognostic factors
      have not been yet defined. We here review the clinical and genetics aspects of
      granulosa tumors, based on a series of 40 children. This national collaborative
      study involved the French Society of Children Cancer and eight clinical
      departments of pediatric endocrinology. We found that early diagnosis of a tumor,
      revealed by clinical signs of hyperoestrogeny, is an important prognostic factor.
      The pathophysiology of these tumors is still debatable and several cellular- and
      molecular-abnormal signals could be implicated in their development. The role of
      growth factors and oncogenes through the signaling pathway of MAP kinase is still
      discussed. According to our data, FSH signaling-transduction pathway, such as a
      constitutionally activated Galphas, could also be implicated in the induction of
      granulosa cell proliferation and seems to modulate the invasiveness of the tumor.
      Last, we have described a low-expression pattern or an extinction of an ovarian
      determination gene, FOXL2, which is related to a worse prognosis of this tumor.

PMID- 19119049
TI  - [Effects of electrostimulation (Veinoplus) on lower limbs venous insufficiency
      related symptoms during pregnancy. Preliminary study].
AB  - OBJECTIVE: To assess if electrostimulation of lower limbs relieves lower limbs
      venous insufficiency-related symptoms during pregnancy. PATIENTS AND METHODS: A
      two-step study was conducted. First, a monocentric prospective preliminary study
      including 30 pregnant women was conducted to assess the effects of
      electrostimulation on fetal monitoring and uterine contractions. Then, a
      multicentric prospective non-randomised study including 58 pregnant women with a
      gestational age between 23 and 33 weeks of amenorrhoea was conducted to evaluate
      the electrostimulation treatment. This evaluation was based on a clinical
      examination performed pre- and post-treatment, a CIVIQ questionnaire filled out
      pre- and post-treatment and a daily diary filled out by the patient during
      treatment duration. Treatment duration was 21 days including two daily treatment
      sequences of 20 min. Three groups of patients were identified based on initial
      intensity of venous insufficiency-related symptoms (group 1 minor symptoms, group
      2 moderate symptoms, group 3 severe symptoms). RESULTS: Preliminary study showed
      no interferences between electrostimulation and fetal cardiac rhythm, uterine
      contractions and maternal uterine and fetal umbilical arteries Doppler.
      Concerning the evaluation of the electrostimulation: in group 1,
      electrostimulation significantly reduced heavy legs sensation (p<0,001) and
      calves pain (p=0,02) between the beginning and the end of the treatment. The four
      scores calculated with the CIVIQ questionnaire decreased after treatment and a
      significant reduction was noted for generalised pain feeling (p=0,04) and
      psychological impact (p=0,03). In group 2, a significant decrease was noted for
      tiredness (p<0,001), heavy legs sensation (p<0,001), calves pain (p<0,001) and
      edema (p=0,02) between the beginning and the end of the treatment. The four
      scores calculated with the CIVIQ questionnaire significantly decrease after 21
      days of treatment. In group 3, a significant decrease of heavy legs sensation
      (p=0,03) and calves and malleoli perimeters (p<0,05) was noted. After 21 days of
      treatment, the four scores calculated with the CIVIQ questionnaire significantly
      decrease (p<0,05). When comparing the three groups, beneficial effects of the
      treatment are most marked in group 2 regarding subjective symptoms, CIVIQ
      questionnaire scores and leg pain. According to the patients, effectiveness and
      tolerance of the treatment ranged from good to excellent in the three groups.
      DISCUSSION AND CONCLUSION: Electrostimulation is an effective and well-tolerated
      treatment of lower limbs venous insufficiency-related symptoms in pregnant women.
      Its use during pregnancy did not show any effects on fetus and pregnancy.

PMID- 19119050
TI  - [Models to predict non sentinel lymph node status in breast cancer patients with
      metastatic sentinel lymph node].
AB  - In breast cancer, nine models have been developed to predict non SN status in
      patients with SN metastasis. Four models are nomograms: the Memorial Sloan
      Kettering Cancer Center nomogram (MSKCC nomogram), the nomogram of Degnim et al.
      (Mayo nomogram), the nomogram of Pal et al. (Cambridge nomogram), and the
      nomogram of Kohrt et al. (Stanford nomogram). Three models are scoring systems:
      the Tenon score, the score from the M.D. Anderson Cancer Center (MDA score), and
      the score of Saidi et al. Finally, two are recursive partitioning tools developed
      by Kohrt et al. Before being used in routine, these models have to be validated
      in independent populations based on discrimination and calibration. However, the
      main issue is their clinical utility based not only on the low false negative
      rate but also its potential to discriminate patients with a low risk of non SN
      involvement. Several institutions have tested the MSKCC nomogram, with AUC
      ranging from 0.58 to 0.86. It was not validated by four studies which did not
      recommend its use even in patients with micrometastasis.The external validation
      of the Tenon score confirmed its relevance with an AUC of 0.82.

PMID- 19119051
TI  - Cavitation occurrence around ultrasonic dental scalers.
AB  - Ultrasonic scalers are used in dentistry to remove calculus and other
      contaminants from teeth. One mechanism which may assist in the cleaning is
      cavitation generated in cooling water around the scaler. The vibratory motion of
      three designs of scaler tip in a water bath has been characterised by laser
      vibrometry, and compared with the spatial distribution of cavitation around the
      scaler tips observed using sonochemiluminescence from a luminol solution. The
      type of cavitation was confirmed by acoustic emission analysed by a 'Cavimeter'
      supplied by NPL. A node/antinode vibration pattern was observed, with the maximum
      displacement of each type of tip occurring at the free end. High levels of
      cavitation activity occurred in areas surrounding the vibration antinodes,
      although minimal levels were observed at the free end of the tip. There was also
      good correlation between vibration amplitude and sonochemiluminescence at other
      points along the scaler tip. 'Cavimeter' analysis correlated well with luminol
      observations, suggesting the presence of primarily transient cavitation.

PMID- 19119052
TI  - Prevalence of restless legs syndrome: a community-based study from Argentina.
AB  - BACKGROUND AND PURPOSE: The number of restless legs syndrome (RLS) prevalence
      studies performed outside Europe and North America remains small. We conducted a
      community-based study to estimate the relative prevalence of RLS in Argentina.
      PATIENTS AND METHODS: A total sample of 471 participants from high (Buenos Aires)
      and low population density areas (three cities with <35,000 inhabitants),
      completed a self-assessment questionnaire, including the International Restless
      Legs Syndrome Study Group (IRLSSG) diagnostic criteria, to determine RLS
      symptoms. RESULTS: In the present study, the four RLS criteria were reported in
      20.2%. In accordance with other studies, we found a female/male ratio of 3:1,
      with women being younger than men. However, RLS prevalence in "clinically
      significant" participants, that is symptoms present at least two or more times a
      week, were 10.8% (12.4% in participants from high population density versus 2.60%
      in participants from low population density areas). CONCLUSIONS: In the present
      study, RLS appears as a common disorder in this population. The RLS prevalence
      found is in agreement with some epidemiological reports from the American and
      European populations but it is significantly higher than the prevalence reported
      for Native South Americans (i.e., 0.8-3.2%). These differences could be explained
      by the composition of the Argentinean population with predominantly European
      roots. Taking into account the significant impact of RLS on health and quality of
      life, our study represents a preliminary approach to characterize this chronic
      disease in this community.

PMID- 19119053
TI  - Parolees' physical closeness to health service providers: a study of California
      parolees.
AB  - We studied a sample of parolees and health service providers in the state of
      California in 2005-2006 to examine the relative physical closeness to health
      providers (and the potential demand of these providers) of parolees based on
      their demographic and prior offending characteristics. Although African-American
      and Latino parolees have more health providers nearby, these providers have
      considerably more potential demand. The health providers near long-term prisoners
      and sex offenders have more potential demand. The results suggest inequity in
      access to services, as minority parolees and those with greater needs may live
      near more impacted providers. The results also suggest some differences in access
      based on rural, suburban, or urban location.

PMID- 19119054
TI  - The influence of increasing sacroiliac joint force closure on the hip and lumbar
      spine extensor muscle firing pattern.
AB  - The prone hip extension (PHE) test is commonly used in the evaluation of lumbo
      pelvic dysfunction. It has been suggested that altered motor control identified
      by the PHE test can be improved with the application of compression force across
      the pelvis, to increase force closure on the sacroiliac joint (SIJ). This
      repeated measure study design investigated the effect of three levels of pelvis
      compression (0N, 50N, 100N) on the muscle firing pattern during the PHE test in
      20 asymptomatic male subjects tested on two occasions 4-weeks apart. The right
      gluteus maximus, right semitendinosus and bilateral lumbar erector spinae were
      analyzed using surface electromyography (EMG). Subjects were instructed to
      perform right hip extension in prone position while maintaining knee-extension in
      each measurement condition. Compared with the onset of the semitendinosus muscle,
      gluteus maximus became active 263.3+/-99.5 ms later with no pelvic compression,
      183.5+/-77.9 ms later with 50N compression, 91.5+/-49.7 ms later with 100N
      compression. While significant differences (alpha=0.05) were found in EMG onset
      for gluteus maximus under different levels of pelvis compression, this was not
      the case for the erector spinae, which had an inconsistent pattern of temporal
      onset and was not influenced by the level of pelvis compression force.

PMID- 19119055
TI  - Simulation of brain tumors in MR images for evaluation of segmentation efficacy.
AB  - Obtaining validation data and comparison metrics for segmentation of magnetic
      resonance images (MRI) are difficult tasks due to the lack of reliable ground
      truth. This problem is even more evident for images presenting pathology, which
      can both alter tissue appearance through infiltration and cause geometric
      distortions. Systems for generating synthetic images with user-defined
      degradation by noise and intensity inhomogeneity offer the possibility for
      testing and comparison of segmentation methods. Such systems do not yet offer
      simulation of sufficiently realistic looking pathology. This paper presents a
      system that combines physical and statistical modeling to generate synthetic
      multi-modal 3D brain MRI with tumor and edema, along with the underlying
      anatomical ground truth, Main emphasis is placed on simulation of the major
      effects known for tumor MRI, such as contrast enhancement, local distortion of
      healthy tissue, infiltrating edema adjacent to tumors, destruction and
      deformation of fiber tracts, and multi-modal MRI contrast of healthy tissue and
      pathology. The new method synthesizes pathology in multi-modal MRI and diffusion
      tensor imaging (DTI) by simulating mass effect, warping and destruction of white
      matter fibers, and infiltration of brain tissues by tumor cells. We generate
      synthetic contrast enhanced MR images by simulating the accumulation of contrast
      agent within the brain. The appearance of the the brain tissue and tumor in MRI
      is simulated by synthesizing texture images from real MR images. The proposed
      method is able to generate synthetic ground truth and synthesized MR images with
      tumor and edema that exhibit comparable segmentation challenges to real tumor
      MRI. Such image data sets will find use in segmentation reliability studies,
      comparison and validation of different segmentation methods, training and
      teaching, or even in evaluating standards for tumor size like the RECIST criteria
      (response evaluation criteria in solid tumors).

PMID- 19119056
TI  - David and Goliath: what can the tiny weed Arabidopsis teach us to improve biomass
      production in crops?
AB  - In the next decades, the world market for plant-derived products is expected to
      expand exponentially. Not only do we rely on plants to feed the growing world
      population, but plants will also play a pivotal role in providing a significant
      part of our increasing energy demands. Whereas in the 1960s the green revolution
      contributed to increase plant productivity, it is expected that biotechnological
      advances will further boost biomass production and plant yield. To do this
      effectively, it will be necessary to understand how the molecular machinery that
      determines yield parameters operates. Although of no direct economic
      significance, the model plant Arabidopsis can be used to find genes and
      regulatory networks controlling biomass production, which, in turn, can be
      applied for further growth improvement in other species including cereals.

PMID- 19119057
TI  - Proton-induced fluorescent switching of a new 2D-pi-A type vinylcyanoacetate
      pyran dye.
AB  - A new 2D-pi-A type vinylcyanoacetate-pyran dye, ethyl 2-(2,6-bis(2-butoxy-4
      (diethylamino)styryl)-4H-pyran-4-ylidene)-2-cyanoacetate (BDPC) was prepared by
      condensation reaction. The chemical structures of all the intermediates and the
      BDPC dye are characterized by (1)H NMR, MS. It showed interestingly
      solvatochromic and solvatofluorchromic properties in various solvents. Its LUMO
      and HOMO values were obtained by the theoretical calculation. The fluorescent
      intensity of BDPC dye can be reversibly selected by protonation/deprotonation of
      the amine moiety via control of intramolecular charge transfer (ICT), leading to
      a fluorescent molecular switch with two distinguished "on" and "off" states.

PMID- 19119058
TI  - Optical, structural and thermodynamic properties of the interaction between
      tradimefon and serum albumin.
AB  - The biological toxicity of a chloric pesticide, tradimefon to bovine serum
      albumin (BSA) were studied by fluorescence and absorption spectroscopy. The
      fluorescence quenching mechanism analysis indicates the quenching of BSA by TDF
      was caused by BSA-TDF complex formation and electrostatic interaction played
      major role in the reaction. The number of binding sites n and observed binding
      constant K(b) was measured by fluorescence quenching method. The thermodynamic
      parameters DeltaH(theta), DeltaG(theta), DeltaS(theta) at different temperatures
      were calculated, and the distance r between donor (BSA) and acceptor (TDF) was
      obtained according to Forster theory of non-radiation energy transfer. Three
      dimensional fluorescence spectra, circular dichroism (CD) spectra and synchronous
      fluorescence spectra were used to investigate the structural change of BSA
      molecules with addition of TDF and the mechanism of binding reaction was analyzed
      at molecular level.

PMID- 19119059
TI  - FT-IR, FT-Raman and DFT calculations of 4-chloro-2-(3,4
      dichlorophenylcarbamoyl)phenyl acetate.
AB  - FT-IR and FT-Raman spectra of 4-chloro-2-(3,4-dichlorophenylcarbamoyl)phenyl
      acetate were recorded and analyzed. Synthesis and elemental analysis are also
      reported. The vibrational wavenumbers of the compound have been computed on the
      basis of density functional theory using B3LYP/6-31G* basis set. The predicted
      infrared intensities and Raman activities are reported.

PMID- 19119060
TI  - Synthesis and anti-fungicidal activity of some transition metal complexes with
      benzimidazole dithiocarbamate ligand.
AB  - Seven transition metal complexes of benzimidazole ligand (HL) are reported and
      characterized based on elemental analyses, IR, solid reflectance, magnetic
      moment, molar conductance and thermal analyses (TGA and DTA). From the obtained
      data, the complexes were proposed to have the general formulae
      [MX(2)(HL)(H(2)O)].yH(2)O, where M=Mn(II), Co(II), Ni(II), Cu(II), Zn(II),
      Cr(III); X=Cl(-), SO(4)(2-) and y=0-4. The molar conductance data revealed that
      all the metal chelates were non-electrolytes. From the magnetic and solid
      reflectance spectra, it was found that the geometrical structure of these
      complexes is octahedral. The thermal behaviour of these chelates showed that the
      hydrated complexes loss water molecules of hydration in the first step followed
      immediately by decomposition of the anions and ligand molecules in the subsequent
      steps. Fungicidal activity of the prepared complexes and free ligand was
      evaluated against three soil borne fungi. Data obtained showed the higher
      biological activity of the prepared complexes than the parent Schiff base ligand.
      Formulation of the most potent complex was carried out in the form of 25% WP.
      Fungicidal activity of the new formulation was evaluated and compared with the
      standard fungicide Pencycuron (Monceren 25% WP). In most cases, the new
      formulation possessed higher fungicidal activity than the standard fungicide
      under the laboratory conditions.

PMID- 19119061
TI  - DNA interaction studies of a platinum(II) complex, PtCl(2)(NN) (NN=4,7-dimethyl
      1,10-phenanthroline), using different instrumental methods.
AB  - The Pt(II) complex, PtCl(2)(4,7-Me(2)phen) (4,7-Me(2)phen=chelating dinitrogen
      ligand: 4,7-dimethyl-1,10-phenanthroline) was synthesized and characterized by
      spectroscopic ((1)H, (13)C NMR) and elemental analysis techniques. Binding
      interaction of this complex with calf thymus (CT) DNA has been investigated by
      emission, absorption, circular dichroism, viscosity and DNA thermal denaturation
      studies. The complex displays significant binding properties to the CT DNA. In
      fluorimeteric studies, the binding mode of complex with CT DNA was studied by
      using methylene blue as a fluoresce probe. As evidenced by the increasing
      fluorescence of methylene blue-DNA solutions in presence of increasing amount of
      complex, PtCl(2)(NN) complex is able to displace the methylene blue intercalated
      into DNA completely as to indicate intercalation. Furthermore, mentioned complex
      induces detectable changes in the CD spectrum of CT-DNA, an increase in T(m)
      value, and an increase in its viscosity. The experimental results showed that
      Pt(II) complex bound to DNA by an intercalative mode of binding.

PMID- 19119062
TI  - Spectroscopic characterizations and biological studies on newly synthesized
      Cu(2+) and Zn(2+) complexes of first and second generation dendrimers.
AB  - The novel Cu(II) and Zn(II) complexes of first and second generation
      poly(propylene amine) dendrimers (PPA), comprising 1,8-naphthalimde units on
      periphery have been synthesized. These new complexes were characterized by
      elemental analysis, molar conductivity, spectral methods (IR, (1)H NMR and UV-vis
      spectra) and thermal analysis (TG and DTG) techniques. From elemental analysis as
      well as thermal studies it has found that the first generation dendrimer behaves
      as bidentate ligand and forming chelates with 1:2 (ligand:metal) and 1:4
      (ligand:metal) stoichiometry for second generation dendrimer. Different kinetic
      parameters namely activation energy (DeltaE*), enthalpy of activation (DeltaH*),
      entropy of activation (DeltaS*) and free energy change of activation (DeltaG*)
      are calculated using Coats-Redfern equation. The antibacterial activity of
      dendrimers and their complexes was evaluated against some Gram positive and
      negative bacteria.

PMID- 19119063
TI  - Template synthesis and physico-chemical characterization of 14-membered
      tetraimine macrocyclic complexes, [MLX(2)] [M=Co(II), Ni(II), Cu(II) and Zn(II)].
      DNA binding study on [CoLCl(2)] complex.
AB  - The template condensation reaction between glyoxal and 1,8-diaminonaphthalene
      resulted a few novel mononuclear 14-membered tetraimine macrocyclic complexes of
      the type, [MLX(2)] [M=Co(II), Ni(II), Cu(II) and Zn(II), for X=Cl or NO(3)]. The
      stoichiometry and the nature of the complexes have been deduced from the results
      of elemental analyses and conductance data. The formation of macrocyclic
      framework has been inferred from the appearance of imine upsilon(CN) and
      upsilon(MN) band in IR spectra and the resonance signals observed in (1)H and
      (13)C-NMR spectra. However, the overall geometry of the complexes has been
      assigned on the positions of bands in electronic spectra and magnetic moment
      data. The distortion in Cu(II) complexes has been deduced on EPR data. The
      thermal behavior of these complexes has been studied by TGA analysis. Absorption
      and circular dichroism studies on the complex proved a significant binding to
      calf thymus DNA.

PMID- 19119064
TI  - Barrett's oesophagus; acid and the human papilloma virus?

PMID- 19119065
TI  - Are anabolic-androgenic steroid users polysubstance users?

PMID- 19119066
TI  - Health-enhancing physical activity behaviour and related factors in postpartum
      women with recent gestational diabetes mellitus.
AB  - This is one of the first studies to explore known preventive behaviours for type
      2 diabetes (T2DM) among women with recent gestational diabetes (GDM), and the
      first to do so in a representative population sample. The aim of this study was
      to describe the prevalence of health-enhancing physical activity (PA) and explore
      its association with psychosocial and sociodemographic factors, in postnatal
      women with recent GDM. Cross-sectional telephone surveys were conducted among
      Queensland women with a recent history (>or=6 months and <or=3 years since
      diagnosis) of GDM (N=331), which included measures on PA behaviour, social
      support and self-efficacy for regular PA. The prevalence of health-enhancing PA
      among women with recent GDM was 37.2%. In multivariate analysis, both social
      support (OR=1.06, 95% CI 1.03-1.09) and self-efficacy (OR=1.04, 95% CI 1.004
      1.07) were significantly associated with health-enhancing PA. The findings from
      this study demonstrate the need for postnatal follow-up to increase PA levels in
      women with recent GDM as this may reduce the risk of developing type 2 diabetes
      (T2DM) in this at-risk population. Strategies that address social support and
      self-efficacy for PA may be effective in increasing health-enhancing PA among
      women with recent GDM.

PMID- 19119067
TI  - Changes in physiological and stroking parameters during interval swims at the
      slope of the d-t relationship.
AB  - The slope of the distance-time relationship from maximal 200 and 400 m bouts
      (S(200-400)) has been increasingly employed for setting training intensities in
      swimming. However, physiological and mechanical responses at this speed are
      poorly understood. Thus, this study investigated blood lactate, heart rate (HR),
      stroke rate (SR), stroke length (SL) and RPE responses to an interval swimming
      set at S(200-400) in trained swimmers. In a 50-m pool, twelve athletes (16.5+/
      1.2 yr, 176+/-7 cm, 68.4+/-5.4 kg, and 7.8+/-2.5% body fat) performed maximal 200
      and 400 m crawl trials for S(200-400) determination (1.28+/-0.05 m/s).
      Thereafter, swimmers were instructed to perform 5 x 400 m at this speed with 1.5
      min rest between repetitions. Three athletes could not complete the set
      (exhaustion at 21.0+/-3.1 min). For the remaining swimmers (total set
      duration=32.0+/-1.3 min) significant increases (p<0.05) in blood lactate (5.7+/
      0.8-7.9+/-2.4 mmol/l), SR (29.6+/-3.2-32.1+/-4.1 cycles/min), HR (169+/-11-181+/
      8 bpm) and RPE (13.3+/-1.6-16.3+/-2.6) were observed through the IS. Conversely,
      SL decreased significantly (p<0.05) from the first to the fifth repetition
      (2.48+/-0.22-2.31+/-0.24 m/cycle). These results suggest that interval swimming
      at S(200-400) represents an intense physiological, mechanical and perceptual
      stimulus that can be sustained for a prolonged period by most athletes.

PMID- 19119068
TI  - The L-type Ca(2+) channel as a potential mediator of pathology during alterations
      in cellular redox state.
AB  - The L-type Ca(2+) channel is the main route for calcium influx into cardiac
      myocytes and an important determinant of calcium homeostasis. There is now
      considerable evidence that the function of the L-type Ca(2+) channel is
      influenced by the cell's redox state. Reactive oxygen species such as hydrogen
      peroxide and superoxide can regulate biological function by directly altering the
      thiol redox state of proteins. Under conditions where cellular redox state
      varies, L-type Ca(2+) channel function and diastolic calcium levels can be
      significantly altered. This article will present the evidence for alterations in
      L-type Ca(2+) channel function by reactive oxygen species and the potential role
      for the channel in development of acute electrophysiological instability or
      chronic pathological remodelling under conditions of persistent oxidative stress.

PMID- 19119069
TI  - Evidence for a causal role of oxidative stress in the myocardial complications of
      insulin resistance.

PMID- 19119070
TI  - NICE guidance on familial hypercholesterolaemia: all sugar and spice?

PMID- 19119071
TI  - Where on the healthcare continuum should we invest? The case for primary care?
AB  - Cardiovascular diseases and particularly coronary heart disease are associated
      with the major personal and economic health burden in Australia. They are also
      the major cause of health inequalities. The associated economic burden is
      projected to increase markedly with ageing of the population and decrease in case
      fatality rates with acute events such as myocardial infarction. Prevention has
      recently been listed second among the priorities of the newly formed National
      Health and Hospitals Reform Commission. It is logical that strategies to prevent
      CVD events should impact across the healthcare continuum. These should include
      population-wide measures to counter the epidemic of overweight, targeted cost
      effective approaches to high-risk asymptomatic individuals, more effective
      management of acute events and systems of care to support implementation of
      evidence-based secondary prevention therapies. Recent cost-utility analyses
      support the proposition that the general practice environment should be a
      particular focus for CHD primary and secondary prevention approaches.

PMID- 19119073
TI  - Reassessment of radiation risks from electrophysiology procedures compared to
      coronary angiography.
AB  - BACKGROUND: Electrophysiology (EP) procedures have been reported to carry a
      significantly greater radiation risk than that of coronary angiography (CA). This
      is largely due to numerous reports linking severe deterministic radiation effects
      to long procedure and fluoroscopy times (FTs). This study documents low radiation
      doses achieved by strategies involving operator training and education as well as
      equipment and technique optimisation to reduce radiation risks. METHODS: Records
      relating to 732 diagnostic EP and 1744 therapeutic EP procedures performed
      between January 2002 and December 2007 were analysed. Data from 1458 diagnostic
      only CA procedures performed in 2006 was used for comparison. For each procedure
      type, FT, number of digital frames acquired and estimated effective dose (E) were
      compared. RESULTS: Although the FT for CA procedures is significantly less than
      for therapeutic EP procedures (FT for diagnostic EP being similar), EP procedures
      generally are associated with lower E, the exception being procedures for atrial
      fibrillation (AF). CONCLUSION: Through the application of a comprehensive
      exposure minimisation strategy, the radiation risk to patients undergoing
      diagnostic and, therapeutic EP procedures (except AF ablation procedures) is
      significantly less than that faced by patients undergoing CA. E, however, is
      heavily dependent on procedure type and as such care must be taken in undertaking
      generalised comparisons for audit and benchmarking purposes.

PMID- 19119072
TI  - Congenital left atrial appendage aneurysm: a case report and brief review of
      literature.
AB  - A 28-year-old woman with congenital aneurysm of the left atrial appendage was
      successfully treated by aneurysmectomy and is reported for its rarity. The exact
      diagnosis is relatively easy to make by contrast echocardiography, magnetic
      resonance imaging, and/or computerised tomographic angiography, provided the
      possibility is entertained. Because of supraventricular arrhythmias and systemic
      thromboembolism, surgical resection was deemed the best curative option to avoid
      further episodes and recurrence. Published reports detailing the diagnostic
      evaluation and surgical management for congenital left atrial appendage aneurysm
      are also discussed.

PMID- 19119074
TI  - Hybrid procedure for acute severe aortic regurgitation in an uncorrected adult
      tetralogy of Fallot.
AB  - Adult survivors of surgically uncorrected complex tetralogy of Fallot [TOF] with
      multiple aorto-pulmonary coronary arteries [MAPCAs] are unusual and the
      development of severe aortic regurgitation [AR] due to endocarditis is a rare and
      difficult problem to manage. We report a successful hybrid approach utilising
      temporary balloon occlusion of the collaterals during the cross-clamp time as a
      strategy to allow adequate brain perfusion and safe aortic root replacement.

PMID- 19119075
TI  - Methicillin resistant Staphylococcus aureus endocarditis in an Australian
      tertiary hospital: 1991-2006.
AB  - BACKGROUND: Methicillin resistant Staphylococcus aureus (MRSA) endocarditis is
      increasing in frequency and has a high mortality. This condition has not been
      specifically described in an Australian population previously. AIM: To describe
      the characteristics, management and outcomes of patients with MRSA endocarditis
      in an Australian hospital and identify trends in this group over 16 years.
      METHODS: Retrospective case series of MRSA endocarditis patients between 1991 and
      2006. RESULTS: Between 1991 and 2006, 27 patients were managed for MRSA
      endocarditis. This group consisted of 18 males (67%). The median age was 64
      years. Infection was related to a prosthetic valve or annular ring in 10 patients
      (37%). The most common comorbidities were diabetes mellitus 8 (30%) and
      malignancy 8 (30%). Nosocomial acquisition occurred in 16 (59%), non-nosocomial
      healthcare associated acquisition in 10 (37%) and community acquisition in 1
      (4%). Management was with a single antimicrobial agent in 5 (19%) and combination
      antimicrobial therapy in 22 (81%). Surgery was undertaken in 16 patients (59%).
      The mortality was 66%. Over this time there was increased non-nosocomial
      acquisition and presentations to non-tertiary hospitals. There was no clear
      improvement in survival over the 16 years. CONCLUSION: In this Australian
      setting, MRSA endocarditis was mostly nosocomial or healthcare associated. Common
      characteristics were older patients with multiple co-morbidities. Despite high
      rates of combination antibiotic therapy and surgery, mortality was very high.
      There is a need for randomised comparative antibiotic studies.

PMID- 19119076
TI  - Cell therapy for heart disease: great expectations, as yet unmet.
AB  - Regenerative medicine is often touted as an achievement of the new millennium,
      but many approaches to improve health by stimulating the organism's own capacity
      for healing have existed for a long time. Some components of today's regenerative
      medicine, however, are indeed fundamentally new developments, and one of those is
      the concept of increasing the number of contractile cells in the heart to cure
      heart failure, either by stimulating intrinsic regeneration processes or by
      transplanting exogenous cells. The aim of this paper is to review the current
      status of some key aspects of cell therapy and obstacles to clinical translation.

PMID- 19119077
TI  - Advances in coronary microvascular dysfunction.
AB  - Considerable focus has been directed towards coronary arterial disease in the
      management of coronary heart disease, however the coronary microcirculation plays
      a major role in the regulation of coronary blood flow. Thus while we have
      multiple medical and revascularisation therapies to treat large vessel coronary
      artery disease, therapies directed towards the microcirculation are very limited.
      This review paper summarises important aspects of coronary microvascular
      dysfunction including (a) methods of assessment, (b) clinical classification of
      associated disorders, (c) possible pathophysiological mechanisms, and (d)
      potential therapies. Hence this will provide important background to advancing
      our understanding and management of coronary heart disease by targeting the
      coronary microcirculation.

PMID- 19119078
TI  - Bronchogenic cysts of the lung: report of 29 cases.
AB  - BACKGROUND: Intrapulmonary bronchogenic cysts are congenital anomalies of the
      tracheobronchial tree and foregut. The aim of this retrospective study was to
      review the diagnosis, clinical and histological features, operative techniques,
      outcomes and follow-up of intrapulmonary bronchogenic cysts treated in a single
      institute. METHODS: Twenty-nine patients with intrapulmonary bronchogenic cysts
      were treated surgically between 1990 and 2005. There were 17 female and 12 male
      patients and their ages ranged from 7 to 68 years. Patients were divided into two
      groups according to surgical procedure. Resection (lobectomy or wedge resection)
      was performed on Group I (n=18), and partial excision with de-epithelisation was
      performed on Group II (n=11). RESULTS: Twenty-five patients (86.2%) were
      symptomatic. Cough and sputum were the most common symptoms. Twenty-four of the
      29 BCs were simple cysts (82.7%) whereas 5 (17.3%) were complicated cysts.
      Postoperative hospital stay was 4.55+/-0.86 days in group I and 6.54+/-3.34 days
      in group II (P=0.172). Complications in Group I were pneumonia in one case and
      wound infection in two cases; prolonged air leakage were observed in two cases of
      Group II. No statistical difference was determined between the complication rates
      of the two groups (P=0.91). However a significant difference was determined
      between the complication rates of simple and complicated cysts (P=0.026). Two
      cases in Group II showed recurrence, whereas no recurrence occurred in Group I.
      (P=0.065) No postoperative mortality was observed in any of the groups.
      CONCLUSIONS: All bronchogenic cysts should be treated surgically. We believe that
      partial excision with de-epithelisation may be an alternative to resection in
      symptomatic patients with limited respiratory capacity.

PMID- 19119079
TI  - Breast cancer follow up: a randomised controlled trial comparing point of need
      access versus routine 6-monthly clinical review.
AB  - AIM: To examine a model of care for breast cancer patients based on the concept
      of point of need access and investigate the effectiveness of this model compared
      to routine 6-monthly clinical reviews. DESIGN: A parallel randomised controlled
      trial was used to examine point of need access to specialist care via the nurse
      specialist, compared to routine hospital based 6-monthly clinical review at year
      two post breast cancer diagnosis. A total of 237 patients were recruited to the
      study. METHODS: Outcome measures at baseline, 9 and 18 months included
      psychological morbidity using the GHQ12 questionnaire, quality of life using the
      FACT-B plus endocrine subscale, fear and isolation. An analysis of covariance was
      used to detect changes over time. Recurrences and methods of detection were
      recorded as secondary outcome measures. RESULTS: Two hundred and fourteen
      patients completed the study. Overall patients were not exposed to risks of
      increased psychological morbidity (p=0.767) or decline of quality of life
      (p=0.282) when routine review was discontinued and no significant differences
      were detected during an 18-month period. Patients not receiving regular review
      did not feel isolated, and at the end of 18 months did not wish to return to 6
      monthly clinical reviews. The presentation of recurrences and short symptom
      history demonstrate that the recurrences observed were unlikely to have been
      detected at a routine visit. CONCLUSIONS: Point of need access is acceptable to
      the majority of patients. Although a third of patients may wish to maintain a
      regular review, patient choice is important. Findings suggest that after 2 years
      following the diagnosis of breast cancer there is no evidence to support the view
      that regular clinical review improves psychological morbidity or quality of life.
      Patients do not appear to be compromised in terms of early detection of
      recurrence. Point of need access can be provided by suitably trained specialist
      nurses and provides a fast, responsive management system at a time when patients
      really need it.

PMID- 19119080
TI  - Lysophosphatidic acid (LPA) and its receptors.
AB  - Lysophosphatidic acid (LPA), a bioactive phospholipid, and its family of cognate
      G protein-coupled receptors have demonstrated roles in many biological functions
      in the nervous system. To date, five LPA receptors have been identified, and
      additional receptors may exist. Most of these receptors have been genetically
      deleted in mice toward identifying biological and medically relevant roles. In
      addition, small molecule agonists and antagonists have been reported. Here we
      review recent data on the nervous system functions of LPA signaling, and
      summarize data on reported agonists and antagonists of LPA receptors.

PMID- 19119081
TI  - Interaction of imatinib with liposomes: voltammetric and AFM characterization.
AB  - The interaction of imatinib with 1,2-dipalmitoyl-sn-glycero-3-phosphocholine
      (DPPC) and 2-oleoyl-1-stearoyl-sn-glycero-3-phosphocholine (OSPC) liposomes and
      the adsorption of DPPC and OSPC were studied using atomic force microscopy (AFM)
      at highly oriented pyrolytic graphite (HOPG) and differential pulse voltammetry
      at glassy carbon electrode (GCE). The HOPG induces the rupture of the liposomes
      and allows the lipids to adsorb along one of the three axes of symmetry of the
      HOPG basal planes, forming well-ordered lamellar structures. After interaction,
      both DPPC monolayers and DPPC-imatinib complexes are adsorbed onto HOPG. The OSPC
      imatinib complexes self-organize only into ordered but larger domains of parallel
      stripes that maintain the threefold symmetry of the HOPG, due to an easier
      imatinib penetration into the unsaturated OSPC liposome bilayers. The
      voltammetric results show that upon interaction, the electrochemical active
      moiety of imatinib is incorporated into the lipid bilayer becoming unavailable to
      the GCE surface for oxidation, leading to local structural modifications of the
      lipid bilayer which were also electrochemically detected. A model is proposed for
      the liposome-imatinib interaction considering that imatinib interacts primarily
      by van der Waals and hydrogen bonds with the phosphatidylcholine headgroups,
      leading to defects in the liposome bilayer and allowing further incorporation of
      imatinib into the liposome lamellae.

PMID- 19119082
TI  - Dynamic rejection of colloidal particles with generating dextran by enzymatic
      reaction.
AB  - Dextransucrase forms a complex with dextran during an enzymatic reaction with
      sucrose. Using its enzymatic character, we performed a continuous and dynamic
      rejection of colloidal particles by generating dextran with dextransucrase
      immobilized in an inorganic porous membrane. Inorganic membranes having 1.9 and
      3.0 U/g of immobilized dextransucrase, and 4.1 and 9.4 mg/g of generated dextran,
      respectively, had constant rejection percentages for 55 and 100 nm colloidal
      particles in permeating solutions. On the other hand, permeating sucrose
      solutions containing colloidal particles through a dextran-immobilized membrane
      dynamically increased the rejection percentages of the colloidal particles owing
      to dextran generation via enzymatic reaction. The dynamic increase was due to the
      gradually generating dextran dynamically occupying the membrane pore with its
      steric volume.

PMID- 19119083
TI  - Determination of a potent urokinase-type plasminogen activator, UK-356,202, in
      plasma at pg/mL levels using column-switching HPLC and fluorescence detection.
AB  - A rapid, sensitive and selective method using column-switching HPLC with
      fluorescence detection has been developed for the determination of UK-356,202, a
      potent urokinase-type plasminogen activator, in human plasma. A structural isomer
      of UK-356,202 is used as an internal standard. The lower limit of quantification
      is 20 pg/mL and the method is linear over a 100-fold concentration range. UK
      356,202 is extracted from plasma simply through the removal of proteins by
      precipitation with acetonitrile. The HPLC system comprises three columns and the
      cycle time is 9.5 min per sample. The eluate from the extraction column is heart
      cut onto a trace enrichment cartridge which is then back-flushed onto a narrow
      bore Supelco ABZ+ Plus analytical column. The method has been used to analyze
      many thousands of samples from clinical and toxicological studies support. Its
      ruggedness is demonstrated by the use of a single extraction column for the
      analysis of over 1200 clinical samples.

PMID- 19119084
TI  - Quantitative measurements of corticosteroids in ex vivo samples using on-line SPE
      LC/MS/MS.
AB  - Abnormal elevation of 11beta-HSD1 activities in tissues, such as fat and brain,
      may contribute to the development of the abdominal obesity and Alzheimer disease,
      and the inhibition of 11beta-HSD1 might be beneficial to the management of these
      diseases. To assess the effects of pharmacologic inhibitors of 11beta-HSD1, we
      developed a fast LC/MS/MS method to quantify corticosteroids in minced tissue
      samples in the presence of 11beta-HSD substrates. The novel on-line SPE-LC/MS/MS
      method was developed with dual binary gradient and a throughput of 4.5
      min/sample. A total of six corticosteroids (cortisol, cortisone, corticosterone,
      dehydrocorticosterone, dexamethasone, and dehydrodexamethasone) were studied. The
      lower limit of quantitation from 0.40 to 11.4 fmol and 4.5 orders magnitude of
      dynamic range were obtained for these six compounds. Three novel enzymatic bi
      products, all isomers of cortisol, were observed in the liver or fat samples. Two
      of them were identified by matching the HPLC retention times and MS/MS spectra
      with authentic compounds. The potential interferences of these isomers and their
      removal are discussed.

PMID- 19119085
TI  - In situ cell culture monitoring on a Ti-6Al-4V surface by electrochemical
      techniques.
AB  - In this work, the in situ interaction between Ti-6Al-4V alloy and osteoblastic
      cells has been studied by electrochemical techniques as a function of time. The
      interaction has been monitored for cell adhesion and growth of human osteoblastic
      Saos-2 cells on Ti-6Al-4V samples. The study has been carried out by
      electrochemical techniques, e.g., studying the evolution of corrosion potential
      with exposure time and by electrochemical impedance spectroscopy. The impedance
      results have been analyzed by using different equivalent circuit models that
      simulate the interface state at each testing time. The adhesion of the
      osteoblastic cells on the Ti-6Al-4V alloy leads to surface areas with different
      cell coverage rates, thus showing the different responses in the impedance
      diagrams with time. The effect of the cells on the electrochemical response of Ti
      6Al-4V alloy is clearly seen after 4 days of testing, in which two isolated and
      well-differentiated time constants are clearly observed. One of these is
      associated with the presence of the cells and the other with a passive film on
      the Ti-6Al-4V alloy. After 7 days of culture, the system is governed by a
      resistive component over a wide frequency range which is associated with an
      increase in the cell coverage rate on the surface due to the extracellular
      matrix.

PMID- 19119086
TI  - Mechanism for converting Al2O3-containing borate glass to hydroxyapatite in
      aqueous phosphate solution.
AB  - The effect of replacing varying amounts (0-2.5 mol.%) of B2O3 with Al2O3 in a
      borate glass on (1) the conversion of the glass to HA in an aqueous phosphate
      solution and (2) the compressive strength of the as-formed HA product was
      investigated. Samples of each glass (10 x 10 x 8 mm) were placed in 0.25 M K2HPO4
      solution at 60 degrees C, and the conversion kinetics to HA were determined from
      the weight loss of the glass and the pH of the solution. The structure and
      composition of the solid reaction products were characterized using X-ray
      diffraction, Fourier transform infrared spectroscopy and scanning electron
      microscopy. While the conversion rate of the glass to HA decreased considerably
      with increasing Al2O3 content, the microstructure of the HA product became denser
      and the compressive strength of the HA product increased. The addition of SiO2 to
      the Al2O3-containing borate glass reversed the deterioration of the conversion
      rate, and produced a further improvement in the strength of the HA product. The
      compressive strength of the HA formed from the borate glass with 2.5 mol.% Al2O3
      and 5 mol.% SiO2 was 11.1 +/- 0.2 MPa, which is equal to the highest strengths
      reported for trabecular bone. The results indicated that simultaneous additions
      of Al2O3 and SiO2 could be used to control the bioactivity of the borate glass
      and to enhance the mechanical strength of the HA product. Furthermore, the HA
      product formed from the glass containing both SiO2 and Al2O3 could be applied to
      bone repair.

PMID- 19119087
TI  - Defining the learning curve for video-assisted thyroidectomy.
AB  - BACKGROUND AND AIM: Several studies have demonstrated that endoscopic
      thyroidectomy is a safe technique. Aim of the study is to evaluate the
      feasibility of video-assisted thyroidectomy (VAT) performed by a junior surgeon.
      MATERIALS AND METHODS: We consider 67 consecutive standard VAT gasless
      approaches. VAT was performed by an under 35-years-old surgeon trained in basic
      laparoscopy tutored by an experienced surgeon. Outcome measures were operative
      and hospitalization times, incision length, and complications. Conversion to open
      surgery was defined as the need to perform a longer incision. To establish the
      number of procedures required before achieving a safe VAT technique, procedures
      were divided into three chronological groups of about 30 lobectomies (Groups 1,
      2, and 3). RESULTS: Success rates of VAT were 90% in group 1, 97% group 2, 100%
      group 3 respectively (P<0.05). Most conversions were due to bleeding. In group 1,
      the overall mean operative time was 111 min, group 2, 93 min, group 3, 86 min
      (P<0.03). Mean length of incision significantly increased from the initial
      incision: group 1, +1.3 cm, group 2, +0.9, group 3, +0.5 cm (P>0.05). Group 3 had
      a faster recovery after surgery. The incidences of temporary hypoparathyroidism
      were 8.9%. The incidences of temporary RLN injury were 2.9%. CONCLUSIONS: To date
      there are no recommendations regarding the amount of endoscopic training required
      to safely perform VAT, but our experience demonstrated that surgeon's age cannot
      be considered having a negative effects on results. Success of VAT technique was
      considerably associated with experience: improved operative variables and safe
      technique were seen after 30 lobectomies.

PMID- 19119089
TI  - The first year of modernizing medical careers: are national standards in plastic
      surgical training being met?

PMID- 19119088
TI  - Does near total thyroidectomy offer advantage over total thyroidectomy in terms
      of postoperative hypocalcemia?
AB  - Total thyroidectomy (TT) has emerged as a surgical option in the surgical
      treatment of patients with multinodular goiter. TT carries potential risk to all
      parathyroid glands and both recurrent laryngeal nerve. The aims of this study are
      to evaluate the difference between serum calcium levels before and after total
      and near total thyroidectomy and to compare the rate of postoperative
      hypocalcemia according to surgical procedures. This prospective study included
      143 consecutive patients undergoing surgical therapy for non-toxic multinodular
      goiter. Patients were randomly assigned to surgical procedures. Patients in group
      1 (n=75) performed TT, and patients in group 2 (n=68) performed near total
      thyroidectomy (NTT). The difference between serum calcium levels and percentage
      decrease in serum calcium levels before and after thyroidectomy were calculated.
      TT had a 33-fold (OR: 33.1; 95% CI: 7.5-145.02) increased risk for hypocalcemia.
      Moreover, TT had a 8-fold (OR: 8.09; 95% CI: 3-21.4) and a 27-fold (OR: 27.9; 95%
      CI: 3.5-219.6) higher risk than NTT for moderate and severe percentage decreases
      in serum calcium level, respectively. NTT can offer an advantage over TT in terms
      of postoperative hypocalcemia in the patients with benign multinodular goiter.

PMID- 19119090
TI  - Pedicled TRAM flap unaffected by clindamycin hypersensitivity reaction.

PMID- 19119091
TI  - Hematopoietic stem cells do not depend on N-cadherin to regulate their
      maintenance.
AB  - According to the "osteoblastic niche" model, hematopoietic stem cells (HSCs) are
      maintained by N-cadherin-mediated homophilic adhesion to osteoblasts at the bone
      marrow endosteum. In contrast to this model, we cannot detect N-cadherin
      expression by HSCs, and most HSCs do not localize to the endosteal surface. It
      has nonetheless been suggested that HSCs express low levels of N-cadherin that
      regulate HSC maintenance. To test this, we conditionally deleted N-cadherin from
      HSCs and other hematopoietic cells in adult Mx-1-Cre(+)N-cadherin(fl/-) mice. N
      cadherin deficiency had no detectable effect on HSC maintenance or hematopoiesis.
      N-cadherin deficiency did not affect bone marrow cellularity or lineage
      composition, the numbers of colony-forming progenitors, the frequency of HSCs,
      the ability of HSCs to sustain hematopoiesis over time, or their ability to
      reconstitute irradiated mice in primary or secondary transplants. Loss of N
      cadherin does not lead to HSC depletion. N-cadherin expression by HSCs is not
      necessary for niche function.

PMID- 19119092
TI  - Reviewing medical books: a quarter century of observations.

PMID- 19119093
TI  - Small RNAs in development and disease.
AB  - MicroRNAs (miRNAs) and short interfering RNAs (siRNAs) are classes of regulatory
      small RNA molecules, ranging from 18 to 24 nucleotides in length, whose roles in
      development and disease are becoming increasingly recognized. They function by
      altering the stability or translational efficiency of messenger RNAs (mRNAs) with
      which they share sequence complementarity, and are predicted to affect up to one
      third of all human genes. Computer algorithms and microarray data estimate the
      presence of nearly 1000 human miRNAs, and direct examination of candidate miRNAs
      has validated their involvement in various cancers, disorders of neuronal
      development, cardiac hypertrophy, and skin diseases such as psoriasis. This
      article reviews the history of miRNA and siRNA discovery, key aspects of their
      biogenesis and mechanism of action, and known connections to human health, with
      an emphasis on their roles in skin development and disease.

PMID- 19119094
TI  - Self-esteem and body satisfaction among late adolescents with acne: results from
      a population survey.
AB  - BACKGROUND: The association of acne and self-evaluation is barely explored among
      late adolescents in the general population. OBJECTIVE: We sought to explore self
      esteem, body satisfaction, and acne among 18-year-old young adults at a community
      level. METHODS: We conducted a questionnaire-based survey among 3775 late
      adolescents. RESULTS: Our response rate was 80%. The prevalence of acne was
      13.5%. Girls and boys with acne had significantly more depressive symptoms, lower
      self-attitude, more feelings of uselessness, fewer feelings of pride, lower self
      worth, and lower body satisfaction than those without acne. In a regression model
      adjusting for body mass index and depressive symptoms, acne explained
      significantly poor self-attitude for boys only (odds ratio 2.07 [confidence
      interval 1.10; 3.88]) and poor self-worth for girls only (odds ratio 1.88
      [confidence interval 1.23; 2.88]). LIMITATIONS: Not all items of the self-esteem
      instrument were included. CONCLUSIONS: At age 18 years, acne is related to self
      evaluation independent of body mass index and depressive symptoms.

PMID- 19119095
TI  - The impact of psoriasis on health care costs and patient work loss.
AB  - BACKGROUND: There are few comprehensive estimates of the cost of psoriasis in the
      United States. OBJECTIVE: We sought to quantify the incremental direct medical
      and indirect work loss costs associated with psoriasis. METHODS: A de-identified
      claims database from 31 self-insured employers during the period 1998 to 2005 was
      used. Patients with at least two psoriasis diagnosis claims (N = 12,280) were
      compared with 3 control subjects (matched on year of birth and sex) without
      psoriasis. Multivariate two-part regression analysis was used to isolate the
      incremental cost of psoriasis by controlling for comorbidities and other
      confounding factors. RESULTS: After multivariate adjustment, the incremental
      direct and indirect costs of psoriasis were approximately $900 and $600 (P <
      .001) per patient per year, respectively. LIMITATIONS: The database used in this
      study does not contain information on patient out-of-pocket costs or loss of
      productivity costs at work. CONCLUSION: The incremental cost of psoriasis is
      approximately $1500 per patient per year, with work loss costs accounting for 40%
      of the cost burden.

PMID- 19119096
TI  - Unifocality of extramammary Paget disease.
AB  - Extramammary Paget disease is a rare tumor that often is associated with multiple
      recurrences after wide local excision. Over the years, the theory that this tumor
      is multicentric has been accepted without detailed scrutiny. We describe a
      patient with unifocal extramammary Paget disease. Axillary extramammary Paget
      disease was treated with Mohs micrographic surgery and intraoperative cytokeratin
      7 immunostaining. With the use of the information from scouting biopsies and the
      Mohs map, a two-dimensional recreation of the tumor showed two contiguous, thin,
      long, finger-like projections extending from the main body of the tumor.
      Extramammary Paget disease may be a contiguous tumor with a highly irregular
      pattern of spread on the skin. It can have finger-like projections beyond the
      main body of the tumor. These subclinical projections may not be observed with
      routine hematoxylin-eosin staining. Cytokeratin 7 immunostaining is required to
      visualize Paget cells that extend beyond the main body of the tumor.

PMID- 19119097
TI  - Sampling of melanocytic nevi for research purposes: a prospective, pilot study to
      determine effect on diagnosis.
AB  - BACKGROUND: Research on melanocytic nevi predominantly utilizes formalin-fixed,
      paraffin-embedded tissue, largely limiting research to morphologic and
      immunohistochemical observations. Withholding portions of fresh nevus tissue for
      molecular studies could result in the loss of important diagnostic material.
      OBJECTIVE: This study prospectively evaluated melanocytic nevi for histologic
      homogeneity to determine if using a portion for research would have affected
      diagnosis. METHODS: Thirty-three subjects were enrolled in a prospective study in
      which pigmented lesions were chosen for biopsy on a clinical basis. Lesions were
      sectioned and each piece submitted in a separate block (mean, 2.7; range 2-5
      blocks per lesion). Slides from nevi were examined in two phases. In phase I,
      sections of nevi were randomized and a diagnosis was rendered for each section of
      nevus. In phase II, the dermatopathologist reviewed all slides for each nevus as
      a case, similar to the original interpretation of the lesion provided to the
      clinician. Diagnoses from phases I and II were compared with the original
      diagnosis. RESULTS: Case material included 51 melanocytic lesions from 31
      subjects. The phase I diagnosis matched the original diagnosis for 99 of 121
      slides that showed a melanocytic lesion (82%). The phase II diagnosis matched the
      original diagnosis for 45 of 51 specimens (88%). LIMITATIONS: The study was
      limited by: a small number of specimens; the clinician could have chosen
      clinically homogeneous nevi for biopsy; effect of interobserver and intraobserver
      variability on diagnosis. CONCLUSIONS: For the majority of melanocytic nevi in
      this study, the diagnostic information present in one section of a melanocytic
      nevus could be extrapolated to the remainder of the specimen without adverse
      consequences from a diagnostic or therapeutic perspective.

PMID- 19119098
TI  - The use of C3d and C4d immunohistochemistry on formalin-fixed tissue as a
      diagnostic adjunct in the assessment of inflammatory skin disease.
AB  - BACKGROUND: Direct immunofluorescent (DIF) testing defines an important
      diagnostic adjunct in the classification of various inflammatory skin conditions;
      it requires fresh tissue, a laboratory equipped to perform the procedure, and a
      pathologist skilled in its interpretation. Although advances have been made in
      the development of antibodies that can be applied to paraffin-embedded tissue,
      there has been no reported success on the application of paraffin tissue-based
      immunohistochemistry as a potential substitute for DIF testing on skin biopsy
      material. OBJECTIVE: We applied C3d and C4d immunohistochemistry on paraffin
      embedded, formalin-fixed tissue to define a potential application of these two
      antibodies as a diagnostic adjunct in the evaluation of various inflammatory skin
      diseases. DESIGN: A natural language search identified cases submitted for both
      light microscopic and DIF studies from July 2006 to August 2007. We prospectively
      included similar cases encountered from August 2007 to March 2008. We correlated
      the C3d and C4d staining pattern with the DIF and light microscopic findings.
      RESULTS: All cases of scarring discoid lupus erythematosus (LE) (20/20) and
      systemic LE (5/5) showed prominent granular C3d along the dermoepidermal junction
      (DEJ) and a positive lupus band test result in the latter by DIF. All systemic LE
      cases demonstrated granular DEJ C4d with C3d or C4d in blood vessels (BV). There
      was a negative lupus band test result without DEJ C3d or C4d in all cases of
      subacute cutaneous lupus erythematosus (SCLE) (15/15). There were, however,
      deposits of C4d within epidermal keratinocytes (7/7), corresponding to IgG
      decoration of keratinocytes by DIF and the presence of anti-Ro antibodies.
      Dermatomyositis cases showed prominent mural C3d and C4d in BV corresponding to
      C5b-9 by DIF (12/12) and one case of hydroxyurea-induced dermatomyositis lacked
      this staining. Although by DIF all dermatomyositis cases had a negative lupus
      band test result, 25% of cases showed staining for C3d along the DEJ (3/9).
      Bullous pemphigoid cases demonstrated homogenous DEJ C3d (17/17) whereas C4d was
      characteristically negative; there was 100% concordance with linear IgG and C3d
      by DIF. Eighty two percent of pemphigus cases demonstrated prominent
      intercellular C3d and C4d, roughly mirroring the intercellular pattern for IgG
      and complement seen by DIF (9/11). Porphyria cases showed homogeneous and
      granular C3d (11/11) and C4d (7/11), mirroring the vascular immunoglobulin and
      C5b-9 by DIF. All cases of urticarial (5), leukocytoclastic (6), and lymphocytic
      (1) vasculitis exhibited prominent mural C3d and C4d in BV, whereas Henoch
      Schonlein purpura (10/10) showed primarily mural BV C3d without C4d, with IgA by
      DIF. Three cases of relapsing polychondritis showed C3d and C4d within
      chondrocyte nuclei (3/3), in contrast to negative staining in chondrodermatitis
      nodularis helicis (0/2). Hypersensitivity reactions were negative for C3d and
      C4d. LIMITATIONS: The small sample size in each category is a limitation. The
      lack of literature precedent with regard to immunohistochemical assessment of
      extracellular antigens on paraffin-embedded tissue in skin samples is another
      limitation of this study. CONCLUSIONS: When correlated with the light microscopic
      and clinical findings, the C3d and C4d assay has significant application in the
      assessment of select inflammatory skin diseases including vasculopathic
      conditions, collagen vascular disease, and autoimmune vesiculobullous disorder.
      It may prompt further DIF testing or, in some instances, may even define a
      reasonable substitute for DIF and/or add to the morphologic assessment of a
      biopsy specimen submitted for routine light microscopic assessment primarily in
      the setting of autoimmune vesiculobullous disease and collagen vascular disease.

PMID- 19119099
TI  - Androgen receptor expression patterns in Becker's nevi: an immunohistochemical
      study.
AB  - BACKGROUND: Becker's nevus (BN) is a hyperpigmented patch that traditionally
      presents on the upper torso in adolescent males. Previous studies have reported
      an association with increased androgen receptors (ARs) in lesional skin in men
      and women who have associated physical abnormalities. OBJECTIVE: This study was
      conducted to assess the presence of ARs immunohistochemically in female patients
      with BN but no other physical abnormalities and compare this finding with BN in
      males and in normal skin. METHODS: Biopsy specimens from Becker's nevi in 3 women
      and 3 men as well as normal skin in the 3 female subjects were stained with AR
      antibody, and the level of expression in various cutaneous structures was
      measured. RESULTS: ARs were increased in dermal fibroblasts in Becker's nevi
      compared to that found in normal skin. LIMITATIONS: The major limitation of the
      study was the small sample size. CONCLUSION: In BN there is increased AR
      expression in dermal fibroblasts; immunohistochemical staining may aid in making
      the biopsy diagnosis.

PMID- 19119100
TI  - Vasculitis in erythema induratum of Bazin: a histopathologic study of 101 biopsy
      specimens from 86 patients.
AB  - BACKGROUND: Erythema induratum of Bazin is a mostly lobular panniculitis. There
      is considerable controversy in the literature about whether or not vasculitis is
      a histopathologic requirement to establish the diagnosis of erythema induratum of
      Bazin. Even accepting vasculitis as a histopathologic criterion, there is no
      agreement about the nature and size of the involved vessels. OBJECTIVE: The main
      goal of our study was to investigate whether or not vasculitis was present in a
      large series of cases of erythema induratum of Bazin and, when vasculitis was
      found, to determine the nature and localization of the involved vessels. METHODS:
      We studied 101 skin biopsy specimens from 86 patients with clinicopathologic
      diagnosis of erythema induratum of Bazin. Histopathologic criteria required in
      each case to be included in this study were: (1) a mostly lobular panniculitis
      with necrotic adipocytes at the center of the fat lobule; (2) inflammatory
      infiltrate within the fat lobule mostly composed of neutrophils in early lesions
      and granulomatous infiltrate in fully developed lesions; (3) significant fat
      necrosis; and (4) absence of other histopathologic findings that allow a specific
      diagnosis of other lobular panniculitis different from erythema induratum of
      Bazin. We also recorded the nature of the inflammatory cells involving the fat
      lobule, and the lesions were classified into two main categories: (1) early
      lesions, when the inflammatory infiltrate was mainly composed of neutrophils,
      with or without leukocytoclasis; and (2) fully developed lesions, when
      histiocytes and lipophages were the predominant inflammatory cells within the
      involved fat lobule. RESULTS: Some type of vasculitis was evident in 91 cases
      (90.09%). A total of 47 biopsy specimens (46.5%) showed a mostly lobular
      panniculitis with necrotizing vasculitis involving the small vessels, probably
      venules, of the center of the fat lobule. Thirteen biopsy specimens (12.8%)
      showed a mostly lobular panniculitis with vasculitis involving both large septal
      veins and small vessels, probably venules, of the center of the fat lobule.
      Twelve biopsy specimens (11.8%) showed a mostly lobular panniculitis with
      vasculitis involving large septal veins, with no involvement or other septal or
      lobular vessels. Ten biopsy specimens (9.9%) showed a mostly lobular panniculitis
      with vasculitis involving large septal vessels, both arteries and veins, and
      necrotizing vasculitis involving the small vessels, probably venules, of the
      center of the fat lobule. Nine biopsy specimens (8.9%) showed a mostly lobular
      panniculitis with vasculitis involving large septal vessels, both arteries and
      veins, but with no involvement of the small blood vessels of the center of the
      fat lobule. Finally, 10 biopsy specimens (9.9%) showed a mostly lobular
      panniculitis without evidence of septal or lobular vasculitis in serial sections.
      Associated diseases included history of extracutaneous tuberculosis (including
      tuberculosis of the lung, lymph nodes, kidney, or bowel) in 12 cases (13.95%),
      previous episodes of superficial thrombophlebitis of the lower legs in 3 cases
      (3.72%), rheumatoid arthritis in one case (1.16%), Crohn disease in one case
      (1.16%), chronic lymphocytic leukemia in two cases (2.32%), hypothyroidism in two
      cases (2.32%), and positive serology for hepatitis B virus in 4 cases (4.65%) and
      for hepatitis C virus in 5 cases (5.81%). LIMITATIONS: Serial sections were not
      performed in all cases. At least 10 sections were studied in each case. When
      vasculitis was evident in some of these first 10 sections, no further sections
      were cut, but when histopathologic features of vasculitis were not found in the
      first 10 sections, serial sections throughout the specimen were performed looking
      for vasculitis. Because some type of vasculitis was evident in the first 10
      sections of 91 cases, serial sections were performed only in the remaining 10
      cases and they failed to demonstrate clear-cut histopathologic features of
      vasculitis. On the other hand, this is a retrospective study that was performed
      from the histopathologic slides of our files, and only the clinical information
      contained in the report accompanying the biopsy specimen could be recorded.
      CONCLUSIONS: In our experience, vasculitis is present in most lesions of erythema
      induratum of Bazin, and the nature, location, and size of the involved vessels
      is, from more to less frequent, as follows: (1) small venules of the fat lobule;
      (2) both veins of the connective tissue septa and venules of the fat lobule; (3)
      only veins of the connective tissue septa; (4) veins and arteries of the
      connective tissue septa and venules of the fat lobule; and (5) veins and arteries
      of the connective tissue septa. However, in some cases with all clinicopathologic
      features of erythema induratum of Bazin vasculitis could not be demonstrated with
      serial sections throughout the specimen and, therefore, the presence of
      vasculitis should be not considered as a criterion sine qua non for
      histopathologic diagnosis of erythema induratum of Bazin.

PMID- 19119102
TI  - Lipodystrophies and the metabolic syndrome.

PMID- 19119101
TI  - Skin cancers, blindness, and anterior tongue mass in African brothers.

PMID- 19119103
TI  - A critical assessment of composite and coprimary endpoints: a complex problem.

PMID- 19119104
TI  - Dermatology physician extenders: a new risk factor?

PMID- 19119105
TI  - The EuroSCAR study: cannot agree with the conclusions.

PMID- 19119106
TI  - Possible environmental effects of sunscreen run-off.

PMID- 19119111
TI  - Congenital pilar leiomyoma.
AB  - Piloleiomyomas are benign smooth muscle tumors arising from the arrectores
      pilorum muscles in the skin. They usually occur as multiple firm dermal nodules
      located on the extremities and trunk. Solitary lesions are rare. Leiomyomas
      usually develop during adolescence or early adult life. Congenital pilar
      leiomiyoma is an extremely rare entity. We present a case of congenital solitary
      pilar leiomyoma located on the face.

PMID- 19119112
TI  - Dermatoscopy of an invasive melanoma on the upper lip shows possible association
      with Laugier-Hunziker syndrome.
AB  - We report mucosal melanoma of the upper lip in a patient affected by the Laugier
      Hunziker disease. Using dermatoscopy, two distinct parts were identified in the
      same mucosal area: nodular (malignant) and macular (benign). A complete surgical
      excision was performed and the patient has been free of disease for 16 months.

PMID- 19119113
TI  - Massive localized lymphedema: an emerging dermatologic complication of obesity.

PMID- 19119114
TI  - Persistent CD20-negative primary cutaneous marginal zone lymphoma after treatment
      with intralesional rituximab therapy.

PMID- 19119115
TI  - Aquagenic syringeal acrokeratoderma.

PMID- 19119116
TI  - Treatment of juvenile pityriasis rubra pilaris with etanercept.

PMID- 19119117
TI  - Primary pyoderma gangrenosum of the lungs.

PMID- 19119118
TI  - Eruptive keratoacanthoma following topical imiquimod for in situ squamous cell
      carcinoma of the skin in a renal transplant recipient.

PMID- 19119119
TI  - Adalimumab therapy of psoriasis and psoriatic arthritis in a patient with
      cirrhosis of the liver.

PMID- 19119120
TI  - "Strawberry gums" in sarcoidosis.

PMID- 19119121
TI  - Efalizumab treatment associated with Candida colitis.

PMID- 19119122
TI  - Hypopigmented T-cell dyscrasia evolving to hypopigmented mycosis fungoides during
      etanercept therapy.

PMID- 19119123
TI  - Multiple eccrine hidrocystomas treated with glycopyrrolate.

PMID- 19119124
TI  - Acrylate allergy induced by acrylic nails resulting in prosthesis failure.

PMID- 19119125
TI  - Angiokeratoma induced by injection of etanercept for psoriasis.

PMID- 19119126
TI  - Scalp sarcoidosis with systemic involvement.

PMID- 19119127
TI  - Erythema multiforme-like presentation of chronic graft versus host disease.

PMID- 19119128
TI  - Infliximab monotherapy as first-line treatment for adult-onset pityriasis rubra
      pilaris: case report and review of the literature on biologic therapy.
AB  - Pityriasis rubra pilaris (PRP) is a rare, chronic papulosquamous disorder of
      unknown etiology that often progresses to disabling palmoplantar keratoderma and
      erythroderma. There is currently no universally effective treatment for PRP, and
      some cases are resistant to multiple topical and systemic therapies. Systemic
      retinoids, methotrexate, several immunosuppressive agents, fumaric acid esters,
      stanozolol, and phototherapy have all been used with varying degrees of success.
      Recently, a few reports have appeared in the literature concerning the use of
      biologics in combination therapies and/or in refractory PRP cases. We report a
      case of type I adult-onset PRP successfully treated with infliximab monotherapy
      as initial systemic therapy, and provide a comprehensive literature review on
      biologic therapy for PRP. The complete and persistent response to infliximab in
      our patient and in the previously reported cases confirms a role for anti-tumor
      necrosis factor-alfa therapy as an effective option in the treatment of PRP.
      Further studies are warranted to evaluate possible differences in efficacy among
      the different biologics.

PMID- 19119129
TI  - Ichthyosis prematurity syndrome: a well-defined congenital ichthyosis subtype.
AB  - Ichthyosis prematurity syndrome is a rare syndrome characterized by the clinical
      triad of premature birth, thick caseous desquamating epidermis, and neonatal
      asphyxia. We describe two siblings with ichthyosis prematurity syndrome. The
      index patient was born at gestational week 34. Immediately after birth he
      developed respiratory distress and needed intubation. Remarkable skin changes
      were noticed with universal red, edematous and desquamating, spongy skin giving
      an impression of excessive vernix caseosa. Marked regression of the edema and
      ichthyotic scaling was observed within a few weeks. The parents recalled that his
      elder sister had similar but milder skin changes and respiratory distress
      syndrome at birth. Ichthyosis prematurity syndrome was suggested and the
      diagnosis supported by electron microscopy of a skin biopsy specimen showing
      pathognomonic trilamellar membrane aggregations in the stratum corneum and
      stratum granulosum. Diagnosing this syndrome is important to reassure parents,
      obstetricians, and pediatricians about its benign course after complications in
      the perinatal period.

PMID- 19119130
TI  - Photodynamic therapy of onychomycosis caused by Trichophyton rubrum.
AB  - A combination of topical and oral antifungals is widely used to treat
      onychomycosis, but treatment failure is common and oral drugs may cause toxicity
      and potential drug interactions. For this reason, new approaches and strategies
      should be considered. The following case shows that photodynamic therapy (PDT)
      may represent an alternative noninvasive approach to treatment of onychomycosis.

PMID- 19119131
TI  - Comma hairs: a dermatoscopic marker for tinea capitis: a rapid diagnostic method.
AB  - BACKGROUND: Dermatoscopy and videodermatoscopy have been used for several years
      in the diagnosis of skin disorders. OBJECTIVE: We sought to determine whether
      tinea capitis (TC) shows characteristic videodermatoscopy features that may
      facilitate its differentiation from alopecia areata (AA). METHODS: Two patients
      with TC caused by Microsporum canis, confirmed by mycological culture and
      fluorescence under Wood lamp, were examined with videodermatoscopy and results
      were compared with videodermatoscopy results of 12 patients with AA. RESULTS: The
      distinctive and most prominent feature of TC was presence of commalike structures
      (comma hairs). These were accompanied by broken and dystrophic hairs.
      Videodermatoscopy features of AA included exclamation mark hairs, vellus and
      dystrophic/cadaverized hairs, and yellow dots corresponding to hyperkeratotic
      hair follicle plugs. LIMITATIONS: This study was conducted on two patients, both
      with M canis infection. CONCLUSIONS: Comma hairs were observed as a distinctive
      videodermatoscopy feature of M canis-induced TC. This finding was not observed in
      AA, typified generally by exclamation mark hairs.

PMID- 19119132
TI  - Imatinib mesylate-induced repigmentation of vitiligo lesions in a patient with
      recurrent gastrointestinal stromal tumors.
AB  - We report a case of vitiligo with localized repigmentation induced by imatinib
      mesylate. An elderly Chinese man has been characterized with recurrent
      gastrointestinal stromal tumors originated from interstitial cells of Cajal with
      gain-of-function c-kit mutation. His recurrent tumors have responded to imatinib
      mesylate therapy. To our surprise, his decade-long vitiligo was dramatically
      ameliorated by localized repigmentation, which is considered to be the side
      effect of imatinib mesylate. Hypopigmentation induced by imatinib mesylate with
      possible molecular blockage to a melanin-dependent KIT signal has been well
      documented; however, our case with repigmentation suggested that KIT signal of
      melanin formation would be much more sophisticated than we have believed.

PMID- 19119133
TI  - Takayasu disease presenting as malignant pyoderma gangrenosum in a child with
      relapsing polychondritis.
AB  - A 7-year-old Lebanese girl with recently diagnosed relapsing polychondritis had a
      1-month history of several painful ulcerations involving her entire body. Skin
      biopsy was consistent with the diagnosis of pyoderma gangrenosum. She was
      hospitalized and started on intravenous steroids with partial improvement. During
      her hospital stay, she developed right wrist drop. Radiologic studies revealed a
      large aortic aneurysm and an axillary aneurysm compressing the right brachial
      nerve plexus. Pathology of the resected aortic anyeurism confirmed the diagnosis
      of Takayasu's arteritis. The patient was started on infliximab therapy with
      complete resolution of her skin lesions and improvement in hand function.

PMID- 19119134
TI  - Scalp metastasis from malignant fibrous histiocytoma of bone.
AB  - Malignant fibrous histiocytoma (MFH) of bone is a relatively rare primary
      malignant neoplasm and an aggressive tumor, characterized by a high frequency of
      local recurrence and distant metastasis. The most common metastatic site is the
      lung (>80%), followed by bone and regional lymph node. Metastasis to other sites
      is extremely rare. In this report, we describe the skin as being the initial
      metastatic site for MFH of bone. A 42-year-old female presented with a bone tumor
      involving the right proximal tibia. She underwent tumor excision and knee joint
      reconstruction. Histologic examination confirmed a striform-pleomorphic type of
      MFH of bone. Six months postoperatively, the patient developed a scalp
      metastasis. Wide local excision was performed. Six months after the scalp
      operation, the patient was alive with no further relapse. We should keep the skin
      in mind as the possible initial site of metastatic MFH of bone.

PMID- 19119135
TI  - A rare cause of syndromic hypotrichosis: Nicolaides-Baraitser syndrome.
AB  - Nicolaides-Baraitser syndrome (NBS) is a recognizable pattern of human
      malformations so far reported only in 5 patients. This condition is chiefly
      characterized by congenital hypotrichosis, peculiar facial gestalt, short
      metacarpals, interphalangeal swelling, and growth and mental retardation.
      Although skin manifestations represent a prominent NBS feature, no particular
      attention has been paid to this condition in the dermatologic literature. Here,
      we report on the sixth patient with NBS, who requested dermatologic evaluation
      because of congenital sparse scalp hair. An integrated approach that involved the
      dermatologist, clinical geneticist, and radiologist was crucial for diagnostic
      definition. Literature review was carried out to better define the NBS clinical
      spectrum and to perform an in-depth differential diagnosis with other
      malformation syndromes presenting with congenital hypotrichosis.

PMID- 19119136
TI  - Acquired cutis laxa associated with heavy chain deposition disease.
AB  - Acquired cutis laxa (generalized acquired elastolysis) is a condition of unknown
      etiology characterized by a degeneration of elastic fibers in the skin, resulting
      in laxity with reduced elastic recoil. We describe a patient with acquired cutis
      laxa associated with an underlying heavy chain deposition disease. Direct
      immunofluorescence testing of lesional skin demonstrated immunoglobulin G
      deposition on elastic fibers, suggesting that in some cases, cutis laxa may have
      an immune-mediated etiopathogenesis.

PMID- 19119137
TI  - Identification of nitroxyl-induced modifications in human platelet proteins using
      a novel mass spectrometric detection method.
AB  - Nitroxyl (HNO) exhibits many important pharmacological effects, including
      inhibition of platelet aggregation, and the HNO donor Angeli's salt has been
      proposed as a potential therapeutic agent in the treatment of many diseases
      including heart failure and alcoholism. Despite this, little is known about the
      mechanism of action of HNO, and its effects are rarely linked to specific protein
      targets of HNO or to the actual chemical changes that proteins undergo when in
      contact with HNO. Here we study the presumed major molecular target of HNO within
      the body: protein thiols. Cysteine-containing tryptic peptides were reacted with
      HNO, generating the sulfinamide modification and, to a lesser extent, disulfide
      linkages with no other long lived intermediates or side products. The sulfinamide
      modification was subjected to a comprehensive tandem mass spectrometric analysis
      including MS/MS by CID and electron capture dissociation as well as an MS(3)
      analysis. These studies revealed a characteristic neutral loss of HS(O)NH2 (65
      Da) that is liberated from the modified cysteine upon CID and can be monitored by
      mass spectrometry. Upon storage, partial conversion of the sulfinamide to
      sulfinic acid was observed, leading to coinciding neutral losses of 65 and 66 Da
      (HS(O)OH). Validation of the method was conducted using a targeted study of
      nitroxylated glyceraldehyde-3-phosphate dehydrogenase extracted from Angeli's
      salt-treated human platelets. In these ex vivo experiments, the sample
      preparation process resulted in complete conversion of sulfinamide to sulfinic
      acid, making this the sole subject of further ex vivo studies. A global
      proteomics analysis to discover platelet proteins that carry nitroxyl-induced
      modifications and a mass spectrometric HNO dose-response analysis of the modified
      proteins were conducted to gain insight into the specificity and selectivity of
      this modification. These methods identified 10 proteins that are modified dose
      dependently in response to HNO, whose functions range from metabolism and
      cytoskeletal rearrangement to signal transduction, providing for the first time a
      possible mechanistic link between HNO-induced modification and the physiological
      effects of HNO donors in platelets.

PMID- 19119138
TI  - Selectivity in enrichment of cAMP-dependent protein kinase regulatory subunits
      type I and type II and their interactors using modified cAMP affinity resins.
AB  - cAMP regulates cellular functions primarily by activating PKA. The involvement of
      PKAs in various signaling pathways occurring simultaneously in different cellular
      compartments necessitates stringent spatial and temporal regulation. This
      specificity is largely achieved by binding of PKA to protein scaffolds, whereby a
      distinct group of proteins called A kinase anchoring proteins (AKAPs) play a
      dominant role. AKAPs are a diverse family of proteins that all bind via a small
      PKA binding domain to the regulatory subunits of PKA. The binding affinities
      between PKA and several AKAPs can be different for different isoforms of the
      regulatory subunits of PKA. Here we employ a combination of affinity
      chromatography and mass spectrometry-based quantitative proteomics to investigate
      specificity in PKA-AKAP interactions. Three different immobilized cAMP analogs
      were used to enrich for PKA and its interacting proteins from several systems;
      HEK293 and RCC10 cells and rat lung and testis tissues. Stable isotope labeling
      was used to confidently identify and differentially quantify target proteins and
      their preferential binding affinity for the three different cAMP analogs. We were
      able to enrich all four isoforms of the regulatory subunits of PKA and
      concomitantly identify more than 10 AKAPs. A selective enrichment of the PKA RI
      isoforms could be achieved; which allowed us to unravel which AKAPs bind
      preferentially to the RI or RII regulatory domains of PKA. Of the twelve AKAPs
      detected, seven preferentially bound to RII, whereas the remaining five displayed
      at least dual specificity with a potential preference for RI. For some of these
      AKAPs our data provide the first insights into their specificity.

PMID- 19119139
TI  - A DNA polymerase-{alpha}{middle dot}primase cofactor with homology to replication
      protein A-32 regulates DNA replication in mammalian cells.
AB  - alpha-Accessory factor (AAF) stimulates the activity of DNA polymerase
      alpha.primase, the only enzyme known to initiate DNA replication in eukaryotic
      cells ( Goulian, M., Heard, C. J., and Grimm, S. L. (1990) J. Biol. Chem. 265,
      13221-13230 ). We purified the AAF heterodimer composed of 44- and 132-kDa
      subunits from cultured cells and identified full-length cDNA clones using amino
      acid sequences from internal peptides. AAF-132 demonstrated no homologies to
      known proteins; AAF-44, however, is evolutionarily related to the 32-kDa subunit
      of replication protein A (RPA-32) and contains an oligonucleotide/oligosaccharide
      binding (OB) fold domain similar to the OB fold domains of RPA involved in single
      stranded DNA binding. Epitope-tagged versions of AAF-44 and -132 formed a complex
      in intact cells, and purified recombinant AAF-44 bound to single-stranded DNA and
      stimulated DNA primase activity only in the presence of AAF-132. Mutations in
      conserved residues within the OB fold of AAF-44 reduced DNA binding activity of
      the AAF-44.AAF-132 complex. Immunofluorescence staining of AAF-44 and AAF-132 in
      S phase-enriched HeLa cells demonstrated punctate nuclear staining, and AAF co
      localized with proliferating cell nuclear antigen, a marker for replication foci
      containing DNA polymerase-alpha.primase and RPA. Small interfering RNA-mediated
      depletion of AAF-44 in tumor cell lines inhibited [methyl-(3)H]thymidine uptake
      into DNA but did not affect cell viability. We conclude that AAF shares
      structural and functional similarities with RPA-32 and regulates DNA replication,
      consistent with its ability to increase polymerase-alpha.primase template
      affinity and stimulate both DNA primase and polymerase-alpha activities in vitro.

PMID- 19119140
TI  - Hepatic lipid partitioning and liver damage in nonalcoholic fatty liver disease:
      role of stearoyl-CoA desaturase.
AB  - Hepatic lipid overloading mainly in the form of triglycerides is considered a
      prerequisite for the development of nonalcoholic fatty liver disease (NAFLD).
      However, triglyceride accumulation in the liver in response to lipid overflow may
      represent a protective mechanism against lipotoxicity. Our aims were to assess
      the fundamental cellular mechanisms that link lipid compartmentation in
      hepatocytes to liver damage and disease progression in NAFLD by using both in
      vivo dietary models of NAFLD and in vitro cell models of lipid overloading.
      Exposure of murine or human hepatocytes to monounsaturated fatty acids (MUFAs)
      resulted in lipid accumulation without changes in cell viability. In contrast,
      cell incubation with saturated fatty acids (SFAs) significantly decreased cell
      viability and increased caspase activation and apoptosis, with only minor lipid
      droplet accumulation. Genetic or pharmacological inhibition of stearoyl-CoA
      desaturase-1 (SCD1), the enzyme that converts SFA to MUFA, sensitized cells to
      SFA-induced apoptosis. Hepatic SCD1 expression increased in experimental
      steatosis resulting from high fat diet and decreased in a methionine-choline
      deficient (MCD) dietary model of steatohepatitis resulting in the latter
      situation in significantly increased hepatic SFA levels. SCD1(-/-) mice on the
      MCD diet had decreased steatosis and markedly increased hepatocellular apoptosis,
      liver injury, and fibrosis compared with the SCD1(+/+), whereas MUFA feeding
      prevents the MCD-induced injury. In conclusion, this study suggests hepatic SCD1
      plays a key role in prevention of steatohepatitis by partitioning excess lipid
      into MUFA that can be safely stored. This concept has important implications for
      the development of novel treatment strategies for patients with this condition.

PMID- 19119141
TI  - Activation of cytosolic phospholipase A2-{alpha} as a novel mechanism regulating
      endothelial cell cycle progression and angiogenesis.
AB  - Release of endothelial cells from contact-inhibition and cell cycle re-entry is
      required for the induction of new blood vessel formation by angiogenesis. Using a
      combination of chemical inhibition, loss of function, and gain of function
      approaches, we demonstrate that endothelial cell cycle re-entry, S phase
      progression, and subsequent angiogenic tubule formation are dependent upon the
      activity of cytosolic phospholipase A(2)-alpha (cPLA(2)alpha). Inhibition of
      cPLA(2)alpha activity and small interfering RNA (siRNA)-mediated knockdown of
      endogenous cPLA(2)alpha reduced endothelial cell proliferation. In the absence of
      cPLA(2)alpha activity, endothelial cells exhibited retarded progression from G(1)
      through S phase, displayed reduced cyclin A/cdk2 expression, and generated less
      arachidonic acid. In quiescent endothelial cells, cPLA(2)alpha is inactivated
      upon its sequestration at the Golgi apparatus. Upon the stimulation of
      endothelial cell proliferation, activation of cPLA(2)alpha by release from the
      Golgi apparatus was critical to the induction of cyclin A expression and
      efficient cell cycle progression. Consequently, inhibition of cPLA(2)alpha was
      sufficient to block angiogenic tubule formation in vitro. Furthermore, the siRNA
      mediated retardation of endothelial cell cycle re-entry and proliferation was
      reversed upon overexpression of an siRNA-resistant form of cPLA(2)alpha. Thus,
      activation of cPLA(2)alpha acts as a novel mechanism for the regulation of
      endothelial cell cycle re-entry, cell cycle progression, and angiogenesis.

PMID- 19119143
TI  - Suppression of 2,3-oxidosqualene cyclase by high fat diet contributes to liver X
      receptor-alpha-mediated improvement of hepatic lipid profile.
AB  - The liver X receptors (LXRs) sense oxysterols and regulate genes involved in
      cholesterol metabolism. Synthetic agonists of LXRs are potent stimulators of
      fatty acid synthesis, which is mediated largely by sterol regulatory element
      binding protein-1c (SREBP-1c). Paradoxically, an improved hepatic lipid profile
      by LXR was observed in mice fed a Western high fat (HF) diet. To explore the
      underlying mechanism, we administered mice normal chow or an HF diet and
      overexpressed LXRalpha in the liver. The HF diet with tail-vein injection of
      adenovirus of LXRalpha increased the expression of LXR-targeted genes involved in
      cholesterol reverse transport but not those involved in fatty acid synthesis. A
      similar effect was also observed with the use of 22R-hydroxycholesterol, an LXR
      ligand, in cultured hepatocytes. Consequently, SREBP-1c maturation was inhibited
      by the HF diet, which resulted from the induction of Insig-2a. Importantly,
      increased cholesterol level suppressed the expression of 2,3-oxidosqualene
      cyclase (OSC), which led to an increase in endogenous LXR ligand(s). Furthermore,
      siRNA-mediated knockdown of OSC expression enhanced LXR activity and selectively
      up-regulated LXR-targeted genes involved in cholesterol reverse transport. Thus,
      down-regulation of OSC may account for a novel mechanism underlying the LXR
      mediated lipid metabolism in the liver of mice fed an HF diet.

PMID- 19119144
TI  - Invited commentary.

PMID- 19119142
TI  - FTY720 inhibits ceramide synthases and up-regulates dihydrosphingosine 1
      phosphate formation in human lung endothelial cells.
AB  - Novel immunomodulatory molecule FTY720 is a synthetic analog of myriocin, but
      unlike myriocin FTY720 does not inhibit serine palmitoyltransferase. Although
      many of the effects of FTY720 are ascribed to its phosphorylation and subsequent
      sphingosine 1-phosphate (S1P)-like action through S1P(1,3-5) receptors, studies
      on modulation of intracellular balance of signaling sphingolipids by FTY720 are
      limited. In this study, we used stable isotope pulse labeling of human pulmonary
      artery endothelial cells with l-[U-(13)C, (15)N]serine as well as in vitro
      enzymatic assays and liquid chromatography-tandem mass spectrometry methodology
      to characterize FTY720 interference with sphingolipid de novo biosynthesis. In
      human pulmonary artery endothelial cells, FTY720 inhibited ceramide synthases,
      resulting in decreased cellular levels of dihydroceramides, ceramides,
      sphingosine, and S1P but increased levels of dihydrosphingosine and
      dihydrosphingosine 1-phosphate (DHS1P). The FTY720-induced modulation of
      sphingolipid de novo biosynthesis was similar to that of fumonisin B1, a
      classical inhibitor of ceramide synthases, but differed in the efficiency to
      inhibit biosynthesis of short-chain versus long-chain ceramides. In vitro kinetic
      studies revealed that FTY720 is a competitive inhibitor of ceramide synthase 2
      toward dihydrosphingosine with an apparent K(i) of 2.15 microm. FTY720-induced up
      regulation of DHS1P level was mediated by sphingosine kinase (SphK) 1, but not
      SphK2, as confirmed by experiments using SphK1/2 silencing with small interfering
      RNA. Our data demonstrate for the first time the ability of FTY720 to inhibit
      ceramide synthases and modulate the intracellular balance of signaling
      sphingolipids. These findings open a novel direction for therapeutic applications
      of FTY720 that focuses on inhibition of ceramide biosynthesis, ceramide-dependent
      signaling, and the up-regulation of DHS1P generation in cells.

PMID- 19119145
TI  - Sexuality and health care: are we training physical therapy professionals to
      address their clients' sexuality needs?

PMID- 19119147
TI  - Congratulations on the diabetes special issue!

PMID- 19119148
TI  - NO more dogma. Nitric oxide marker in asthma.

PMID- 19119149
TI  - Exhaled nitric oxide: still alive, not laid to rest.

PMID- 19119150
TI  - Extracellular superoxide dismutase haplotypes and acute lung injury: reading into
      the genome to understand mortality?

PMID- 19119151
TI  - Opportunities and challenges in the study of pulmonary arterial hypertension.

PMID- 19119152
TI  - Systemic inflammation and inhaled corticosteroids in COPD.

PMID- 19119153
TI  - Does pharmacotherapy reduce the rate of decline of lung function in COPD?

PMID- 19119154
TI  - On the randomized trial of activated protein C in acute lung injury.

PMID- 19119155
TI  - Recent chronic beryllium disease in residents surrounding a beryllium facility:
      patients' information.

PMID- 19119156
TI  - The European Heart Journal goes global: the road ahead of the editorial team 2009
      2011.

PMID- 19119157
TI  - Reporting clinical trial results.

PMID- 19119158
TI  - CAD/CAM and esthetics.

PMID- 19119159
TI  - Periodontal disease and other diseases.

PMID- 19119160
TI  - Dealing with diabetes.

PMID- 19119164
TI  - An eight-year clinical evaluation of filled and unfilled one-bottle dental
      adhesives.
AB  - BACKGROUND: The strategies for accomplishing resin adhesion to dentin involve
      surface conditioning, priming and bonding. One-bottle adhesives combine the
      priming and bonding functions in a single solution. In this study, the authors
      compared the eight-year clinical performance of two one-bottle adhesives made by
      different manufacturers. METHODS: The authors placed a total of 99 Class V
      restorations using either a filled, ethanol-based adhesive (OptiBond Solo [OS],
      SDS Kerr, Orange, Calif.) or an unfilled, acetone-based adhesive (Prime & Bond
      2.1 [PB] Dentsply Caulk, Milford, Del.) and a hybrid resin-based composite in 33
      subjects with noncarious cervical lesions. The authors did not bevel the enamel
      margins and used no mechanical retention. They evaluated the restorations at
      baseline and for as long as eight years after placement using modified U.S.
      Public Health Service criteria. They analyzed differences between groups using
      appropriate statistical tests. RESULTS: The authors examined 56 restorations
      after eight years and found retention rates of 69 percent for OS and 59 percent
      for PB. These rates did not differ statistically (P = .449) and were not
      significantly affected by subject or lesion characteristics. The authors noted
      marginal discoloration on 55 percent of the retained OS restorations and on 31
      percent of the retained PB restorations, but they detected no secondary caries
      around any restoration. They noted poor anatomical form and poor marginal
      adaptation in 15 percent and 40 percent of the retained OS restorations,
      respectively. CONCLUSIONS: The performance of both adhesives was good during this
      eight-year clinical trial. The filled, ethanol-based adhesive OS demonstrated
      slightly better bond durability than did the unfilled, acetone-based adhesive PB,
      but the difference between the two materials was not statistically significant.
      CLINICAL IMPLICATIONS: Despite a high incidence of marginal discoloration, the
      one-bottle adhesives evaluated in this study provided good clinical retention of
      Class V restorations without mechanical retention. When the materials are used
      properly, restorations are retained at an acceptable rate through at least eight
      years of clinical service.

PMID- 19119165
TI  - A comparison of the effects of toothbrushing and handpiece prophylaxis on
      retention of sealants.
AB  - BACKGROUND: Tooth surface cleaning before acid etching is considered to be an
      important step in the retention of resin-based pit-and-fissure sealants. METHODS:
      The authors reviewed and summarized instructions for cleaning tooth surfaces from
      five manufacturers of 10 unfilled resin-based sealants marketed in the United
      States. The authors also searched electronic databases for studies that directly
      compared the effects of different surface-cleaning methods on sealant retention
      and for systematic reviews of the effectiveness of sealants. They explored the
      association between surface-cleaning methods and sealant retention in the studies
      included in the systematic reviews. They calculated the summary weighted
      retention rates for studies that used either a handpiece or toothbrush
      prophylaxis. RESULTS: All of the sealant manufacturers' instructions for use
      (IFU) recommended cleaning the tooth before acid etching. None of the IFU
      directly stated that a handpiece was required to perform the cleaning, but five
      IFU implied the use of handpiece prophylaxis. None of the IFU recommended surface
      altering procedures in caries-free teeth. Direct evidence from two clinical
      trials showed no difference in complete sealant retention between surfaces
      cleaned mechanically with pumice or prophylaxis paste and those cleaned with air
      water syringe or dry toothbrushing. Indirect evidence from 10 studies found that
      weighted summary retention by year after sealant placement in studies that used
      toothbrush prophylaxis was greater than or equivalent to values for studies that
      used handpiece prophylaxis. CONCLUSIONS: Levels of sealant retention after
      surface cleaning with toothbrush prophylaxis were at least as high as those
      associated with hand-piece prophylaxis. CLINICAL IMPLICATIONS: This finding may
      translate into lower resource costs for sealant placement.

PMID- 19119166
TI  - The clinician's guide to the literature: interpreting results.
AB  - BACKGROUND: Oral health care professionals must have up-to-date information to
      guide clinical practice. The peer-reviewed literature contains the most reliable
      and current information. The clinical research literature relies on statistical
      analysis of data to make inferences and draw conclusions. In this article, the
      authors explore the fundamental principles that underlie statistical testing.
      CONCLUSIONS AND PRACTICE IMPLICATIONS: Having the fundamental tools to critically
      interpret the results presented in the literature is one of the essential
      elements for appropriately translating clinical research into practice.

PMID- 19119167
TI  - Tetracycline-induced renal failure after dental treatment.
AB  - BACKGROUND: Tetracyclines are broad-spectrum antibiotics used by dental
      practitioners in the treatment of periodontal disease. They generally are safe in
      adults. However, caution is advised in patients who have pre-existing kidney
      disease. CASE DESCRIPTION: A 42-year-old woman with polycystic kidney disease
      received a prescription for tetracycline (250 milligrams, four times daily) after
      undergoing tooth extractions. She developed nausea, vomiting and diarrhea within
      days and end-stage renal disease within two weeks of taking the antibiotic.
      Hemodialysis was required to stabilize the patient's condition. Use of the
      Naranjo nomogram demonstrated an association between the two events. CLINICAL
      IMPLICATIONS: This case illustrates the importance of obtaining a thorough
      medical history and understanding potential adverse drug effects before
      prescribing a common antibiotic.

PMID- 19119168
TI  - Oral bisphosphonate use and the prevalence of osteonecrosis of the jaw: an
      institutional inquiry.
AB  - BACKGROUND: Initial reports of osteonecrosis of the jaw (ONJ) secondary to
      bisphosphonate (BP) therapy indicated that patients receiving BPs orally were at
      a negligible risk of developing ONJ compared with patients receiving BPs
      intravenously. The authors conducted a study to address a preliminary finding
      that ONJ secondary to oral BP therapy with alendronate sodium in a patient
      population at the University of Southern California was more common than
      previously suggested. METHODS: The authors queried an electronic medical record
      system to determine the number of patients with a history of alendronate use and
      all patients receiving alendronate who also were receiving treatment for ONJ.
      RESULTS: The authors identified 208 patients with a history of alendronate use.
      They found that nine had active ONJ and were being treated in the school's
      clinics. These patients represented one in 23 of the patients receiving
      alendronate, or approximately 4 percent of the population. CONCLUSIONS: This is
      the first large institutional study in the United States with respect to the
      epidemiology of ONJ and oral bisphosphonate use. Further studies along this line
      will help delineate more clearly the relationship between oral BP use and ONJ.
      CLINICAL IMPLICATIONS: The findings from this study indicated that even short
      term oral use of alendronate led to ONJ in a subset of patients after certain
      dental procedures were performed. These findings have important therapeutic and
      preventive implications.

PMID- 19119169
TI  - A comparison of a refrigerant and a topical anesthetic gel as preinjection
      anesthetics: a clinical evaluation.
AB  - BACKGROUND: The authors used a split-mouth design to determine the effectiveness
      of a refrigerant compared with that of a topical anesthetic gel in reducing the
      pain experienced during a posterior palatal anesthetic injection. METHODS:
      Sixteen participants received a five-second application of a refrigerant
      (1,1,1,3,3-pentafluoropropane/1,1,1,2-tetrafluoroethane) and a two-minute
      application of a topical anesthetic gel (20 percent benzocaine gel) in the
      posterior palatal area before an injection of a local anesthetic solution was
      administered with a 30-gauge needle. Participants rated the pain they experienced
      after each injection by using a 100-millimeter visual analog scale (VAS) with
      endpoints of "no pain" and "worst possible pain." The authors calculated VAS
      scores by measuring the distance in millimeters from the no pain end of the
      scale. They analyzed data with a paired t test (alpha = .05). RESULTS: The group
      receiving the refrigerant had a mean VAS score of 17.7 +/- 15.3 mm, and the group
      receiving the topical anesthetic gel had a VAS score of 26.2 +/- 18.0 mm. The use
      of the refrigerant compared with the use of topical anesthetic gel significantly
      reduced the pain experienced during administration of local anesthetic injections
      (P = .02). CONCLUSIONS: The use of a refrigerant as a preinjection anesthetic was
      more effective compared with the use of a topical anesthetic gel in reducing the
      pain experienced by participants who received a posterior palatal injection.
      CLINICAL IMPLICATIONS: The potential benefits of using a refrigerant rather than
      a topical anesthetic gel are pain reduction, decreased application time, ease of
      application and avoidance of displeasing taste.

PMID- 19119170
TI  - Dissolution of root canal sealers in EDTA and NaOCl solutions.
AB  - BACKGROUND: Solutions of ethylenediaminetetraacetic acid (EDTA) and sodium
      hypochlorite (NaOCl) have been used as canal irrigants in endodontic treatment.
      The authors conducted a study to compare the ability of these solutions to
      dissolve sealers. METHODS: The authors assessed the solubility of six sealers
      calcium hydroxide, polyketone, zinc oxide-eugenol, silicone and two epoxy resins
      in EDTA and two concentrations of NaOCl (2.5 percent and 5.0 percent). They
      immersed standardized samples (n = 5) of each sealer for two minutes and 10
      minutes. They obtained the mean values of sealer dissolution in solutions by
      calculating the difference between the original preimmersion and postimmersion
      weights to determine the amount of sealer removed. They compared the values via
      factorial analysis of variance. They analyzed differences between the six sealers
      with respect to their solubility in EDTA or NaOCl solutions at two minutes and 10
      minutes by using a one-way analysis of variance (P < .05). RESULTS: In comparison
      with NaOCl solutions, EDTA was markedly superior in dissolving root canal sealers
      (P < .05). There were no significant differences between the two concentrations
      of NaOCl. The two epoxy resins and the silicone-based sealer were of low
      solubility. The zinc oxide-eugenol-based sealer was significantly more soluble
      than were the epoxy resins and the silicone-based sealers. Polyketone and calcium
      hydroxide-based sealers were the most soluble sealers (P < .05). CONCLUSIONS AND
      CLINICAL IMPLICATIONS: The results of this study indicate that during nonsurgical
      endodontic re-treatment, EDTA and NaOCl solutions used for removing smear layer
      aided in the retreatment by dissolving some root canal sealers.

PMID- 19119171
TI  - AXIS inhibition protein 2, orofacial clefts and a family history of cancer.
AB  - BACKGROUND: Cancer and congenital malformations occasionally may have a common
      etiology. The authors investigated whether families with one or more members
      affected by orofacial clefts (that is, families segregating orofacial clefts) had
      an increased cancer incidence when compared with control families. METHODS: The
      authors assessed 75 white families with nonsyndromic cleft lip with or without
      cleft palate (CL/P) and 93 white control families regarding a history of cancer.
      They used chi(2) and Fisher exact tests to determine significant differences.
      They then performed molecular studies with genes in which mutations have been
      independently associated with both cancer and craniofacial anomalies in a total
      of 111 families with CL/P. RESULTS: The families with CL/P reported a family
      history of cancer more often than did control families (P <.001), and they had
      higher rates of specific cancer types: colon (P <.001), brain (P = .003),
      leukemia (P = .005), breast (P = .009), prostate (P = .01), skin (P = .01), lung
      (P = .02) and liver (P = .02). The authors detected overtransmission of AXIS
      inhibition protein 2 (AXIN2) in CL/P probands (P = .003). CONCLUSION: Families
      segregating CL/P may have an increased susceptibility to cancer, notably colon
      cancer. Furthermore, AXIN2, a gene that when mutated increases susceptibility to
      colon cancer, also is associated with CL/P. CLINICAL IMPLICATIONS: People who are
      at a higher risk of developing disease need to adopt a healthier lifestyle,
      including avoiding exposure to risk factors that may interact with their
      genotypes.

PMID- 19119173
TI  - The effects of insurance carrier market power on dentists and patients.
AB  - BACKGROUND: Market power among dental insurance carriers is a carrier's ability
      to reimburse dentists at rates below what would exist in more competitive areas.
      Competition among carriers for dentists' participation in their networks protects
      dentists from highly discounted fees. The authors examined the extent to which
      dental insurance carriers facing less competition increase fee discounts.
      METHODS: The authors selected a sample of dentists from listings of general
      practitioners. They identified 219 metropolitan areas and contacted 11,542
      dentists in those areas by mail, telephone or both. A total of 8,017 dentists
      completed surveys (a response rate of 69.46 percent). The authors' key focus was
      the possible relationship between carrier market power and the size of the fee
      discount. The authors compared discounts across metropolitan areas with their
      differing levels of insurance coverage and carrier market shares. RESULTS:
      Carrier market power was directly related to the sizes of fee discounts. The
      larger discounts were found where there was significant dental insurance coverage
      and few carriers providing this coverage. Dentists' net incomes were
      significantly less in areas with larger fee discounts. CONCLUSIONS AND PRACTICE
      IMPLICATIONS: Dental insurance carrier market power leads to increased fee
      discounts. These higher discounts reduce dentists' earnings. Although the larger
      discounts may result in lower overall patient costs, this patient benefit is
      temporary. Ultimately, the number of practicing dentists in these communities
      will decrease as dentists seek improved practicing conditions elsewhere. This
      reduction will lead to overall fee increases until the earning potential of
      dentists is restored.

PMID- 19119174
TI  - A patient with severe wear on the posterior teeth and minimal wear on the
      anterior teeth.

PMID- 19119175
TI  - The phenomenon of the "cash-poor" practice.

PMID- 19119176
TI  - What should I do about dental assistants who are performing prophylaxes?

PMID- 19119177
TI  - For the dental patient: fluoride: nature's tooth decay fighter.

PMID- 19119178
TI  - The battle to keep or lose skeletal muscle with ageing.

PMID- 19119179
TI  - Maintaining cooperation among cardiac myofilament proteins through thick and
      thin.

PMID- 19119180
TI  - What is adapted in saccadic adaptation?

PMID- 19119181
TI  - Planning the long run.

PMID- 19119182
TI  - Non-oxidative cerebral carbohydrate metabolism.

PMID- 19119183
TI  - Neuroendocrine, metabolic and pharmacological control of feeding behaviour-
      closing in on antiobesity treatment.

PMID- 19119184
TI  - Bacterial infection of Smad3/Rag2 double-null mice with transforming growth
      factor-beta dysregulation as a model for studying inflammation-associated colon
      cancer.
AB  - Alterations in genes encoding transforming growth factor-beta-signaling
      components contribute to colon cancer in humans. Similarly, mice deficient in the
      transforming growth factor-beta signaling molecule, Smad3, develop colon cancer,
      but only after a bacterial trigger occurs, resulting in chronic inflammation. To
      determine whether Smad3-null lymphocytes contribute to increased cancer
      susceptibility, we crossed Smad3-null mice with mice deficient in both B and T
      lymphocytes (Rag2(-/-) mice). Helicobacter-infected Smad3/Rag2-double knockout
      (DKO) mice had more diffuse inflammation and increased incidence of
      adenocarcinoma compared with Helicobacter-infected Smad3(-/-) or Rag2(-/-) mice
      alone. Adoptive transfer of WT CD4(+)CD25(+) T-regulatory cells provided
      significant protection of Smad3/Rag2-DKO from bacterial-induced typhlocolitis,
      dysplasia, and tumor development, whereas Smad3(-/-) T-regulatory cells provided
      no protection. Immunohistochemistry, real-time reverse transcriptase-polymerase
      chain reaction, and Western blot analyses of colonic tissues from Smad3/Rag2-DKO
      mice 1 week after Helicobacter infection revealed an influx of macrophages,
      enhanced nuclear factor-kappaB activation, increased Bcl(XL)/Bcl-2 expression,
      increased c-Myc expression, accentuated epithelial cell proliferation, and up
      regulated IFN-gamma, IL-1alpha, TNF-alpha, IL-1beta, and IL-6 transcription
      levels. These results suggest that the loss of Smad3 increases susceptibility to
      colon cancer by at least two mechanisms: deficient T-regulatory cell function,
      which leads to excessive inflammation after a bacterial trigger; and increased
      expression of proinflammatory cytokines, enhanced nuclear factor-kappaB
      activation, and increased expression of both pro-oncogenic and anti-apoptotic
      proteins that result in increased cell proliferation/survival of epithelial cells
      in colonic tissues.

PMID- 19119187
TI  - Making a science of education.

PMID- 19119185
TI  - Cytosolic viral sensor RIG-I is a 5'-triphosphate-dependent translocase on double
      stranded RNA.
AB  - Retinoic acid inducible-gene I (RIG-I) is a cytosolic multidomain protein that
      detects viral RNA and elicits an antiviral immune response. Two N-terminal
      caspase activation and recruitment domains (CARDs) transmit the signal, and the
      regulatory domain prevents signaling in the absence of viral RNA. 5'-triphosphate
      and double-stranded RNA (dsRNA) are two molecular patterns that enable RIG-I to
      discriminate pathogenic from self-RNA. However, the function of the DExH box
      helicase domain that is also required for activity is less clear. Using single
      molecule protein-induced fluorescence enhancement, we discovered a robust
      adenosine 5'-triphosphate-powered dsRNA translocation activity of RIG-I. The
      CARDs dramatically suppress translocation in the absence of 5'-triphosphate, and
      the activation by 5'-triphosphate triggers RIG-I to translocate preferentially on
      dsRNA in cis. This functional integration of two RNA molecular patterns may
      provide a means to specifically sense and counteract replicating viruses.

PMID- 19119186
TI  - Neuronal activity-induced Gadd45b promotes epigenetic DNA demethylation and adult
      neurogenesis.
AB  - The mammalian brain exhibits diverse types of neural plasticity, including
      activity-dependent neurogenesis in the adult hippocampus. How transient
      activation of mature neurons leads to long-lasting modulation of adult
      neurogenesis is unknown. Here we identify Gadd45b as a neural activity-induced
      immediate early gene in mature hippocampal neurons. Mice with Gadd45b deletion
      exhibit specific deficits in neural activity-induced proliferation of neural
      progenitors and dendritic growth of newborn neurons in the adult hippocampus.
      Mechanistically, Gadd45b is required for activity-induced DNA demethylation of
      specific promoters and expression of corresponding genes critical for adult
      neurogenesis, including brain-derived neurotrophic factor and fibroblast growth
      factor. Thus, Gadd45b links neuronal circuit activity to epigenetic DNA
      modification and expression of secreted factors in mature neurons for extrinsic
      modulation of neurogenesis in the adult brain.

PMID- 19119188
TI  - The transition. Holdren named science adviser, Varmus, Lander to co-chair PCAST.

PMID- 19119189
TI  - Scientific collaboration. Tehran incident threatens U.S.-Iran project.

PMID- 19119190
TI  - Research assessment. U.K. University research ranked; funding impacts to follow.

PMID- 19119191
TI  - Research funding. For many scientists, the Madoff scandal suddenly hits home.

PMID- 19119192
TI  - Planetary impacts. Did the mammoth slayer leave a diamond calling card?

PMID- 19119193
TI  - Coral reefs. Calcification rates drop in Australian reefs.

PMID- 19119194
TI  - Science advisers. Bending the president's ear.

PMID- 19119195
TI  - Brain cancer. A viral link to glioblastoma?

PMID- 19119196
TI  - Polar science. A death in Antarctica.

PMID- 19119197
TI  - Literature citations in the Internet era.

PMID- 19119198
TI  - Narrower focus may be more efficient.

PMID- 19119199
TI  - To each citation, a purpose.

PMID- 19119200
TI  - A cycle of tradition and innovation.

PMID- 19119201
TI  - Comment on "Log or linear? Distinct intuitions of the number scale in Western and
      Amazonian indigene cultures".
AB  - Dehaene et al. (Reports, 30 May 2008, p. 1217) argued that native speakers of
      Mundurucu, a language without a linguistic numerical system, inherently represent
      numerical values as a logarithmically spaced spatial continuum. However, their
      data do not rule out the alternative conclusion that Mundurucu speakers encode
      numbers linearly with scalar variability and psychologically construct space
      number mappings by analogy.

PMID- 19119202
TI  - Environment. "True" conservation progress.

PMID- 19119203
TI  - Astronomy. How old is that star?
AB  - Despite being fundamental in determining its physical state, a star's age cannot
      be measured directly, and estimation methods are imprecise.

PMID- 19119204
TI  - Physics. Cloaking with curved spaces.

PMID- 19119205
TI  - Chemistry. Repair or replacement--a joint perspective.

PMID- 19119206
TI  - Geochemistry. A matter of preservation.

PMID- 19119207
TI  - Education. Farewell, lecture?

PMID- 19119208
TI  - Microbiology. Mosquitoes cut short.

PMID- 19119209
TI  - Adding a T to the three R's. Education & technology. Introduction.

PMID- 19119210
TI  - Video: education and technology.

PMID- 19119211
TI  - NSF rethinks its digital library.

PMID- 19119212
TI  - New landscape for the earth sciences.

PMID- 19119213
TI  - A Nobelist's passionate pursuit of excellence.

PMID- 19119214
TI  - A vision in search of funding.

PMID- 19119215
TI  - Computers as writing instructors.

PMID- 19119216
TI  - Glow lights up Scottish classrooms.

PMID- 19119217
TI  - Korea tries to level the field.

PMID- 19119218
TI  - A personal tutor for algebra.

PMID- 19119219
TI  - Immersive interfaces for engagement and learning.
AB  - Immersion is the subjective impression that one is participating in a
      comprehensive, realistic experience. Interactive media now enable various degrees
      of digital immersion. The more a virtual immersive experience is based on design
      strategies that combine actional, symbolic, and sensory factors, the greater the
      participant's suspension of disbelief that she or he is "inside" a digitally
      enhanced setting. Studies have shown that immersion in a digital environment can
      enhance education in at least three ways: by allowing multiple perspectives,
      situated learning, and transfer. Further studies are needed on the capabilities
      of immersive media for learning, on the instructional designs best suited to each
      type of immersive medium, and on the learning strengths and preferences these
      media develop in users.

PMID- 19119220
TI  - Technology and informal education: what is taught, what is learned.
AB  - The informal learning environments of television, video games, and the Internet
      are producing learners with a new profile of cognitive skills. This profile
      features widespread and sophisticated development of visual-spatial skills, such
      as iconic representation and spatial visualization. A pressing social problem is
      the prevalence of violent video games, leading to desensitization, aggressive
      behavior, and gender inequity in opportunities to develop visual-spatial skills.
      Formal education must adapt to these changes, taking advantage of new strengths
      in visual-spatial intelligence and compensating for new weaknesses in higher
      order cognitive processes: abstract vocabulary, mindfulness, reflection,
      inductive problem solving, critical thinking, and imagination. These develop
      through the use of an older technology, reading, which, along with audio media
      such as radio, also stimulates imagination. Informal education therefore requires
      a balanced media diet using each technology's specific strengths in order to
      develop a complete profile of cognitive skills.

PMID- 19119221
TI  - Education and training technology in the military.
AB  - The United States Department of Defense (DOD) has contributed to the development
      of various education and training technologies, two of which are computer
      assisted instruction and simulation-based instruction. DOD investment in computer
      assisted instruction has continued from the 1950s to the present. Its
      contributions have ranged from drill and practice to computers capable of
      generating instructional interactions on demand and in real time. DOD investment
      in instructional simulation began with pilot trainers but evolved to include
      computer-controlled simulators serving a wide range of purposes, including
      simulators that are networked for collective education and the training of crews,
      teams, and units. Past and continuing contributions of the DOD in areas such as
      effectiveness, cost-effectiveness, instructional efficiency, and collaborative
      collective activity are worthy of attention.

PMID- 19119222
TI  - Technology and testing.
AB  - Large-scale testing of educational outcomes benefits already from technological
      applications that address logistics such as development, administration, and
      scoring of tests, as well as reporting of results. Innovative applications of
      technology also provide rich, authentic tasks that challenge the sorts of
      integrated knowledge, critical thinking, and problem solving seldom well
      addressed in paper-based tests. Such tasks can be used on both large-scale and
      classroom-based assessments. Balanced assessment systems can be developed that
      integrate curriculum-embedded, benchmark, and summative assessments across
      classroom, district, state, national, and international levels. We discuss here
      the potential of technology to launch a new era of integrated, learning-centered
      assessment systems.

PMID- 19119223
TI  - Video games: a route to large-scale STEM education?
AB  - Video games have enormous mass appeal, reaching audiences in the hundreds of
      thousands to millions. They also embed many pedagogical practices known to be
      effective in other environments. This article reviews the sparse but encouraging
      data on learning outcomes for video games in science, technology, engineering,
      and math (STEM) disciplines, then reviews the infrastructural obstacles to wider
      adoption of this new medium.

PMID- 19119224
TI  - Laptop programs for students.
AB  - With the continuing decline in costs of technology, programs are proliferating
      worldwide to put networked laptop computers into the hands of millions of
      students on a routine basis. The reasons policy-makers support these programs are
      based on economic arguments, equity concerns, and widespread interest in
      education reform. Studies of laptop programs in schools report that they increase
      students' engagement in school, improve technology skills, and have positive
      effects on students' writing. However, evidence of the effectiveness of large
      scale laptop programs in other learning domains is scarce. Research in many
      nations suggests that laptop programs will be most successful as part of
      balanced, comprehensive initiatives that address changes in education goals,
      curricula, teacher training, and assessment.

PMID- 19119225
TI  - Online education today.
AB  - Online education is established, growing, and here to stay. It is creating new
      opportunities for students and also for faculty, regulators of education, and the
      educational institutions themselves. Much of what is being learned by the
      practitioners will flow into the large numbers of blended courses that will be
      developed and delivered on most campuses. Some of what is being learned will
      certainly improve pedagogical approaches and possibly affect other important
      problems, such as the lengthening time to completion of a degree. Online
      education is already providing better access to education for many, and many more
      will benefit from this increased access in the coming years.

PMID- 19119226
TI  - Opening education.
AB  - Spurred by the publication of Massachusetts Institute of Technology
      OpenCourseWare in 2002, the open educational resources (OER) movement, which has
      rapidly expanded and captured the imagination and energy of millions of creators
      and users throughout the world, now faces many opportunities and substantial
      challenges as it moves to become an integral part of the world's educational
      environment. The confluence of the Web and a spirit of sharing intellectual
      property have fueled a worldwide movement to make knowledge and education
      materials open to all for use. OER are content (courses, books, lesson plans,
      articles, etc.), tools (virtual laboratories, simulations, and games), and
      software that support learning and educational practice. OER are free on the Web,
      and most have licenses that allow copyright holders to retain ownership while
      providing specified rights for use in original and modified forms. At the least,
      OER have helped to level the distribution of knowledge across the world. A second
      promise of OER is to help transform educational practices. This article explores
      the history of and promises and challenges for OER.

PMID- 19119227
TI  - Nanodiamonds in the Younger Dryas boundary sediment layer.
AB  - We report abundant nanodiamonds in sediments dating to 12.9 +/- 0.1 thousand
      calendar years before the present at multiple locations across North America.
      Selected area electron diffraction patterns reveal two diamond allotropes in this
      boundary layer but not above or below that interval. Cubic diamonds form under
      high temperature-pressure regimes, and n-diamonds also require extraordinary
      conditions, well outside the range of Earth's typical surficial processes but
      common to cosmic impacts. N-diamond concentrations range from approximately 10 to
      3700 parts per billion by weight, comparable to amounts found in known impact
      layers. These diamonds provide strong evidence for Earth's collision with a rare
      swarm of carbonaceous chondrites or comets at the onset of the Younger Dryas cool
      interval, producing multiple airbursts and possible surface impacts, with severe
      repercussions for plants, animals, and humans in North America.

PMID- 19119228
TI  - Mott insulating state in ultraclean carbon nanotubes.
AB  - The Mott insulating state is a manifestation of strong electron interactions in
      nominally metallic systems. Using transport spectroscopy, we showed that an
      energy gap exists in nominally metallic carbon nanotubes and occurs in addition
      to the band gap in small-band-gap nanotubes, indicating that carbon nanotubes are
      never metallic. This gap has a magnitude of approximately 10 to 100 milli
      electron volts and a nanotube radius (r) dependence of approximately 1/r, which
      is in good agreement with predictions for a nanotube Mott insulating state. We
      also observed neutral excitations within the gap, as predicted for this state.
      Our results underscore nanotubes' exceptional capabilities for use in studying
      correlated electron phenomena in one dimension.

PMID- 19119229
TI  - Control of self-assembly of DNA tubules through integration of gold
      nanoparticles.
AB  - The assembly of nanoparticles into three-dimensional (3D) architectures could
      allow for greater control of the interactions between these particles or with
      molecules. DNA tubes are known to form through either self-association of multi
      helix DNA bundle structures or closing up of 2D DNA tile lattices. By the
      attachment of single-stranded DNA to gold nanoparticles, nanotubes of various 3D
      architectures can form, ranging in shape from stacked rings to single spirals,
      double spirals, and nested spirals. The nanoparticles are active elements that
      control the preference for specific tube conformations through size-dependent
      steric repulsion effects. For example, we can control the tube assembly to favor
      stacked-ring structures using 10-nanometer gold nanoparticles. Electron
      tomography revealed a left-handed chirality in the spiral tubes, double-wall tube
      features, and conformational transitions between tubes.

PMID- 19119230
TI  - Declining coral calcification on the Great Barrier Reef.
AB  - Reef-building corals are under increasing physiological stress from a changing
      climate and ocean absorption of increasing atmospheric carbon dioxide. We
      investigated 328 colonies of massive Porites corals from 69 reefs of the Great
      Barrier Reef (GBR) in Australia. Their skeletal records show that throughout the
      GBR, calcification has declined by 14.2% since 1990, predominantly because
      extension (linear growth) has declined by 13.3%. The data suggest that such a
      severe and sudden decline in calcification is unprecedented in at least the past
      400 years. Calcification increases linearly with increasing large-scale sea
      surface temperature but responds nonlinearly to annual temperature anomalies. The
      causes of the decline remain unknown; however, this study suggests that
      increasing temperature stress and a declining saturation state of seawater
      aragonite may be diminishing the ability of GBR corals to deposit calcium
      carbonate.

PMID- 19119231
TI  - Stretching the envelope of past surface environments: Neoproterozoic glacial
      lakes from Svalbard.
AB  - The oxygen isotope composition of terrestrial sulfate is affected measurably by
      many Earth-surface processes. During the Neoproterozoic, severe "snowball"
      glaciations would have had an extreme impact on the biosphere and the atmosphere.
      Here, we report that sulfate extracted from carbonate lenses within a
      Neoproterozoic glacial diamictite suite from Svalbard, with an age of
      approximately 635 million years ago, falls well outside the currently known
      natural range of triple oxygen isotope compositions and indicates that the
      atmosphere had either an exceptionally high atmospheric carbon dioxide
      concentration or an utterly unfamiliar oxygen cycle during deposition of the
      diamictites.

PMID- 19119232
TI  - Why peer discussion improves student performance on in-class concept questions.
AB  - When students answer an in-class conceptual question individually using clickers,
      discuss it with their neighbors, and then revote on the same question, the
      percentage of correct answers typically increases. This outcome could result from
      gains in understanding during discussion, or simply from peer influence of
      knowledgeable students on their neighbors. To distinguish between these
      alternatives in an undergraduate genetics course, we followed the above exercise
      with a second, similar (isomorphic) question on the same concept that students
      answered individually. Our results indicate that peer discussion enhances
      understanding, even when none of the students in a discussion group originally
      knows the correct answer.

PMID- 19119233
TI  - Regulation of neuronal survival factor MEF2D by chaperone-mediated autophagy.
AB  - Chaperone-mediated autophagy controls the degradation of selective cytosolic
      proteins and may protect neurons against degeneration. In a neuronal cell line,
      we found that chaperone-mediated autophagy regulated the activity of myocyte
      enhancer factor 2D (MEF2D), a transcription factor required for neuronal
      survival. MEF2D was observed to continuously shuttle to the cytoplasm, interact
      with the chaperone Hsc70, and undergo degradation. Inhibition of chaperone
      mediated autophagy caused accumulation of inactive MEF2D in the cytoplasm. MEF2D
      levels were increased in the brains of alpha-synuclein transgenic mice and
      patients with Parkinson's disease. Wild-type alpha-synuclein and a Parkinson's
      disease-associated mutant disrupted the MEF2D-Hsc70 binding and led to neuronal
      death. Thus, chaperone-mediated autophagy modulates the neuronal survival
      machinery, and dysregulation of this pathway is associated with Parkinson's
      disease.

PMID- 19119234
TI  - Signal sequences activate the catalytic switch of SRP RNA.
AB  - The signal recognition particle (SRP) recognizes polypeptide chains bearing a
      signal sequence as they emerge from the ribosome, and then binds its membrane
      associated receptor (SR), thereby delivering the ribosome-nascent chain complex
      to the endoplasmic reticulum in eukaryotic cells and the plasma membrane in
      prokaryotic cells. SRP RNA catalytically accelerates the interaction of SRP and
      SR, which stimulates their guanosine triphosphatase (GTPase) activities, leading
      to dissociation of the complex. We found that although the catalytic activity of
      SRP RNA appeared to be constitutive, SRP RNA accelerated complex formation only
      when SRP was bound to a signal sequence. This crucial control step was obscured
      because a detergent commonly included in the reaction buffer acted as a signal
      peptide mimic. Thus, SRP RNA is a molecular switch that renders the SRP-SR GTPase
      engine responsive to signal peptide recruitment, coupling GTP hydrolysis to
      productive protein targeting.

PMID- 19119235
TI  - Floral iridescence, produced by diffractive optics, acts as a cue for animal
      pollinators.
AB  - Iridescence, the change in hue of a surface with varying observation angles, is
      used by insects, birds, fish, and reptiles for species recognition and mate
      selection. We identified iridescence in flowers of Hibiscus trionum and Tulipa
      species and demonstrated that iridescence is generated through diffraction
      gratings that might be widespread among flowering plants. Although iridescence
      might be expected to increase attractiveness, it might also compromise target
      identification because the object's appearance will vary depending on the
      viewer's perspective. We found that bumblebees (Bombus terrestris) learn to
      disentangle flower iridescence from color and correctly identify iridescent
      flowers despite their continuously changing appearance. This ability is retained
      in the absence of cues from polarized light or ultraviolet reflectance associated
      with diffraction gratings.

PMID- 19119236
TI  - Phage-mediated intergeneric transfer of toxin genes.
AB  - Because bacteriophages generally parasitize only closely related bacteria, it is
      assumed that phage-mediated genetic exchange occurs primarily within species.
      Here we report that staphylococcal pathogenenicity islands, containing
      superantigen genes, and other mobile elements transferred to Listeria
      monocytogenes at the same high frequencies as they transfer within Staphylococcus
      aureus. Several staphylococcal phages transduced L. monocytogenes but could not
      form plaques. In an experiment modeling phage therapy for bovine mastitis, we
      observed pathogenicity island transfer between S. aureus and L. monocytogenes in
      raw milk. Thus, phages may participate in a far more expansive network of genetic
      information exchange among bacteria of different species than originally thought,
      with important implications for the evolution of human pathogens.

PMID- 19119237
TI  - Stable introduction of a life-shortening Wolbachia infection into the mosquito
      Aedes aegypti.
AB  - Most pathogens require a relatively long period of development in their mosquito
      vector before they can be transmitted to a new human host; hence, only older
      insects are of epidemiological importance. The successful transfer of a life
      shortening strain of the inherited bacterial symbiont, Wolbachia, into the major
      mosquito vector of dengue, Aedes aegypti, halved adult life span under laboratory
      conditions. The association is stable, and the Wolbachia strain is maternally
      inherited at high frequency. It is capable of inducing complete cytoplasmic
      incompatibility, which should facilitate its invasion into natural field
      populations and its persistence over time. Our data suggest that targeting
      mosquito age with inherited Wolbachia infections may be a viable strategy to
      reduce the transmission of pathogens such as dengue viruses.

PMID- 19119239
TI  - [Treatment of chronic hepatitis C: efficacy of initial treatment of peginterferon
      alpha-2a versus peginterferon alpha-2b plus ribavirin in naive chronic hepatitis
      C patients].

PMID- 19119240
TI  - [Hepatitis B virus genetic diversity and mutant].
AB  - Hepatitis B virus (HBV) is a partially double stranded DNA virus with genetic
      diversity represented by eight genotypes (A to H). Natural course and response to
      treatment could be affected by HBV genotypes. HBV shows high rates of turn over
      in the absence of proof-reading ability. As a result, large amounts of
      quasispecies are produced naturally or antiviral-associated. HBV consists of four
      open reading frames, namely preS/S gene, precore/core gene, polymerase gene, and
      X gene. Mutations on preS gene can result in undetectable HBsAg even in case that
      HBV is replicating. Surface gene mutation leads to decreased binding affinity to
      anti-HBs, which is associated with a vaccine escape mutant. Precore mutation
      abolishes HBeAg whereas mutations on basal core promoter gene down-regulate the
      HBeAg production. Mutations on basal core promoter are associated with increased
      HBV replication and high incidence of progressive liver diseases such as liver
      cirrhosis and hepatocellular carcinoma. Mutations on polymerase genes are often
      induced by antiviral therapy. Emergence of antiviral-resistant mutation is the
      major cause of treatment failure. Furthermore, existence of prior antiviral
      resistant mutations limits the options of subsequent antiviral agents. Therefore,
      judicious use of antivirals and selection of the most potent drug with the lowest
      resistance rate are of the utmost importance for the prevention of antiviral
      associated mutants. Detailed knowledge and understanding of HBV genetic diversity
      and mutant would be critical to establish strategies for the diagnosis and
      management of HBV infection.

PMID- 19119241
TI  - Changes in liver stiffness during the course of acute hepatitis A.
AB  - BACKGROUNDS/AIMS: In some patients with chronic hepatitis, liver stiffness (LS)
      findings do not reflect fibrosis stage. This study was performed to evaluate
      whether acute liver inflammation could influence LS findings. METHODS: Patients
      with acute hepatitis A admitted to our hospital were included. Hepatitis was
      classified on admission using serum ALT and bilirubin levels as inflammation
      phase, jaundice phase, or recovery phase. Patients who admitted during the
      recovery phase (whose ALT and bilirubin levels fell continuously during
      hospitalization) and therefore, their peak-ALT and peak bilirubin levels could
      not be determined were exduded. Enrolled patients underwent FibroScan during
      hospitalization and after discharge. RESULTS: Seventy-six patients with acute
      hepatitis A were enrolled (median age, 29 years; 46 men and 30 women). Among
      them, 33 (43.4%) and 43 (56.6%) patients were admitted during the inflammation
      phase and jaundice phase, respectively. For patients admitted during the
      inflammation phase, mean (+/-SD) time from symptom-onset day to maximum ALT level
      was 7 (+/-3) days. For all patients, mean time from symptom-onset to maximum
      bilirubin level was 11 (+/-4) days. Mean LS during admission was 8.9 (+/-Pa
      (median, 8.4 kPa). LS was significantly correlated with serum bilirubin level,
      which was the only factor found to be significantly associated with the increased
      LS (>7.08 kPa). In all patients, LS increased gradually from the symptom-onset
      and peaked at 8-9 days later. CONCLUSIONS: Severe hepatic inflammation can affect
      the LS findings and thus, care is required when assessing fibrosis stage using LS
      measurement in patients with severe inflammation.

PMID- 19119242
TI  - [Clinical outcomes and predictive factors of spontaneous survival in patients
      with fulminant hepatitis A].
AB  - BACKGROUNDS/AIMS: The occurrence of acute hepatitis A is increasing and its
      progression to fulminant hepatic failure (FHF) is frequent. We investigated the
      frequency and clinical outcomes of fulminant hepatitis A and also analyzed the
      predictive factors of spontaneous survival. METHODS: A total of 568 patients
      presented with acute hepatitis A from January 2003 to June 2008, of which the 35
      (6.2%) patients with FHF were divided into two groups: spontaneous survival and
      transplant/death. These two groups were compared according to various clinical
      features including the MELD score and King's College Hospital (KCH) criteria.
      RESULTS: The rate of FHF development increased over time among patients with
      acute hepatitis A: 0% in 2003, 3.4% in 2004, 3.2% in 2005, 6.0% in 2006, 7.7% in
      2007, and 13.0% in 2008. Twenty patients (57.1%) showed spontaneous survival, 13
      (37.1%) received liver transplantation, and 5 (14.3%) died during
      hospitalization. The two groups of spontaneous survival (N=20) and
      transplant/death (N=15) showed significant differences in prothrombin time at
      admission and at its worst value, albumin at its worst value, and hepatic
      encephalopathy grade at admission and at its worst value. The MELD score was
      lower in the spontaneous-survival group than in the transplant/death group
      (27.0+/-7.8 vs. 37.0+/-7.1, mean+/-SD; P=0.001). However, KCH criteria did not
      differ significantly between the two groups. On multivariate analysis, HEP grade
      was the only significant predictive factor, being negatively correlated with
      spontaneous survival (OR=0.068, P=0.025). CONCLUSIONS: FHF due to hepatitis A has
      increased in recent years, and in our cohort the HEP grade was closely associated
      with spontaneous survival.

PMID- 19119243
TI  - [Clinical characteristics of 159 cases of acute toxic hepatitis].
AB  - BACKGROUNDS/AIMS: Toxic hepatitis has recently been discovered to be a major
      cause of acute hepatitis. We studied the clinical features and prognosis of
      patients diagnosed with toxic hepatitis at a single institution. METHODS: A
      retrospective analysis was performed using medical records of 159 cases of toxic
      hepatitis that were diagnosed from March 2003 to March 2008. Patients were
      selected based on a RUCAM score of 4 or above. RESULTS: The incidence was higher
      in women (n=97) than in men (n=62). The age (mean+/-SD) of the patients was 51+/
      15 years . The major causes of the disease included the use of Korean traditional
      therapeutic preparations (34.0%), herbal medicines (41.5%), and drugs prescribed
      by a physician (23.9%). At the time of admission, jaundice was the most common
      symptom (41.5%), and the results of a liver serum battery were as follows:
      aspartate aminotransferase, 729.4+/-877.0 IU/L; alanine aminotransferase, 857.1+/
      683.0 IU/L; total bilirubin, 6.4+/-6.5 mg/dL; and alkaline phosphatase, 209.8+/
      130.0 IU/L. The hospitalization period was 10.0+/-9.5 days, and the duration of
      recovery from liver injury was 31.0+/-29.5 days. The factors associated with the
      hospitalization period included the presence of anorexia and the serum levels of
      albumin and bilirubin at the time of admission (P<0.05). A high serum bilirubin
      level and a history of alcohol ingestion were associated with a delayed recovery
      (Plt;0.05). The sex, age, BMI, and duration of medication were not significantly
      related to the hospitalization and recovery periods. CONCLUSIONS: The main cause
      of acute toxic hepatitis in the current study was the use of herbal medicines.
      The severity of liver injury at the time of admission was a major factor
      significantly associated with the hospitalization and recovery periods.

PMID- 19119244
TI  - [Efficacy of initial treatment with peginterferon alpha-2a versus peginterferon
      alpha-2b in combination with ribavirin in naive chronic hepatitis C patients
      living in Daejeon and Chungcheong Province in Korea: a comparative study].
AB  - BACKGROUNDS/AIMS: Peginterferon alpha-2a or -2b is the standard treatment regimen
      in chronic hepatitis C. However, there have been few comparative studies of the
      efficacies of these two types of peginterferon. We evaluated their efficacies in
      combination with ribavirin as a initial treatment for chronic hepatitis C.
      METHODS: Ninety-seven patients were treated with peginterferon alpha-2a (180
      microg/week, n=48) or peginterferon alpha-2b (1.5 microg/kg/week, n=49) plus
      ribavirin (800 mg/day for 24 weeks in genotype non-1 or 1,000-1,200 mg/day for 48
      weeks in genotype 1). Virologic responses including the early virologic response
      (EVR), end-of-treatment response (ETR), sustained virologic response (SVR), and
      adverse effects were analyzed retrospectively. RESULTS: The virologic response
      rates did not differ significantly between peginterferon alpha-2a and -2b: 89.6%
      and 89.7% for EVR, 79.2% and 79.5% for ETR, 72.9% and 73.5% for SVR,
      respectively. Analysis of the virologic responses according to genotype also
      revealed no significant differences in SVR between peginterferon alpha-2a and -2b
      (59.3% vs. 59.7% for genotype 1 and 90.5% vs. 83.3% for genotype non-1,
      respectively), or in adverse effects including flu-like symptom, rash, itching,
      neutropenia, and thrombocytopenia. CONCLUSIONS: We found no significant
      differences in therapeutic efficacies and adverse effects between the alpha-2a
      and -2b types of peginterferon as the initial treatment regimen in naive chronic
      hepatitis C patients.

PMID- 19119245
TI  - [The efficacy of adefovir dipivoxil monotherapy and the incidence of genotypic
      resistance to adefovir dipivoxil in patients with lamivudine-resistant chronic
      hepatitis B infection].
AB  - BACKGROUND/AIMS: Adefovir dipivoxil (ADV) is a nucleotide analogue that inhibits
      wild-type hepatitis B virus (HBV) and lamivudine (LMV)-resistant HBV mutants. The
      aim of this study was to elucidate the efficacy of ADV monotherapy and the
      incidence of genotypic resistance to ADV in patients with LMV-resistant chronic
      HBV infection. METHODS: This study involved 124 patients with chronic HBV
      infection who had received ADV monotherapy due to the presence of LMV-resistant
      HBV mutants. The efficacy of ADV was evaluated by the normalization of serum
      alanine aminotransferase (ALT) level and by the reduction of serum HBV DNA level
      (with cutoff levels of 2x10(4) IU/mL and 2x10(2) IU/mL). The cumulative rate of
      HBeAg loss or seroconversion was assessed in HBeAg-positive patients. The
      development of mutations in the reverse trancriptase region of HBV DNA polymerase
      was evaluated by direct sequencing analysis during ADV monotherapy. RESULTS: The
      mean serum HBV DNA level was 5.94 log10IU/mL. At 12 and 24 months after ADV
      monotherapy, the cumulative rates of serum ALT normalization were 69.4% and
      75.5%, respectively, and those of serum HBV DNA reduction were 79.8% and 89.2%
      for a cutoff level of 2x10(4) IU/mL, and 44.2% and 59.0% for a cutoff of 2x10(2)
      IU/mL. The mean serum HBV DNA levels at 12 and 24 months were significantly lower
      than baseline, at 3.24 and 3.04 log10IU/mL, respectively (P<0.001). At 12 months
      after ADV treatment, the cumulative rates of HBeAg loss and seroconversion were
      15.8% and 10.5%, respectively, and the rtN236T and rtA181T/V mutants in HBV DNA
      polymerase were identified in 25% and 64% of patients, respectively. CONCLUSIONS:
      Although ADV monotherapy is effective, it leads to a high rate of mutations of
      HBV DNA reverse transcriptase gene in patients with chronic HBV infections who
      have LMV-resistant HBV mutants.

PMID- 19119246
TI  - [A case report of treatment with pegylated interferon alpha for lamivudine
      resistant chronic hepatitis B virus infection].
AB  - The wide use of lamivudine in chronic hepatitis B has produced a monotonic
      increase in patients with lamivudine resistance. Therefore, treating lamivudine
      resistance in chronic hepatitis B is a major concern in clinical practice for the
      treatment of hepatitis B virus (HBV). There is conflicting evidence on the
      outcome of pegylated interferon alpha (PEG-IFN alpha) therapy against lamivudine
      resistant HBV, which is due to mutations in the YMDD motif. We experienced a
      patient with chronic hepatitis B who was successfully treated with PEG-IFN alpha
      2a after the development of virologic and biochemical breakthrough during
      lamivudine therapy. Virologic breakthrough was associated with the emergence of
      YMDD mutants 48 months after starting lamivudine therapy. Treatment with PEG-IFN
      alpha-2a for 12 months resulted in an undetectable serum level of HBV DNA and the
      resolution of hepatitis, and the virologic response was maintained over 16 months
      after cessation of PEG-IFN alpha-2a.

PMID- 19119247
TI  - [Treatment with pegylated interferon and ribavirin in a patient with fibrosing
      cholestatic hepatitis due to recurrent hepatitis C after liver transplantation].
AB  - Fibrosing cholestatic hepatitis (FCH) is the most devastating manifestation of
      recurrent hepatitis C in transplant recipients with hepatitis C virus (HCV),
      possibly leading to death or retransplantation. Although FCH was first described
      as a complication of hepatitis B, this manifestation has been well documented in
      association with HCV in the setting of liver transplantation, bone marrow
      transplantation, heart transplantation, and end-stage human immunodeficiency
      virus infection. We report the clinical course and antiviral response in a
      patient with FCH due to recurrent hepatitis C after cadaveric liver
      transplantation who was treated with pegylated interferon alpha-2a and ribavirin.

PMID- 19119248
TI  - [A case of hepatic epithelioid hemangioendothelioma that caused extrahepatic
      metastases without intrahepatic recurrence after hepatic resection].
AB  - Epithelioid hemangioendothelioma is a neoplasm of vascular origin with a low-to
      intermediate malignant potential and is one of the rare sarcomas arising from the
      liver. Its etiology is unknown and its clinical outcome is unpredictable. There
      is no generally accepted therapeutic strategy because of its rarity and the
      variable natural course between hemangioma and angiosarcoma. We report a case of
      a 64-year old woman who underwent hepatic resection due to epithelioid
      hemangioendothelioma in the right lobe that progressed to extrahepatic metastases
      of the bone, pleura, and peritoneum 22 months later. However, after resection
      there was no primary hepatic recurrence.

PMID- 19119249
TI  - [Mucin hypersecreting cholangiocarcinoma].

PMID- 19119250
TI  - [Focal nodular hyperplasia-like nodule].

PMID- 19119252
TI  - Hepatocyte nuclear factor 1-alpha mutation in normal glucose-tolerant subjects
      and early-onset type 2 diabetic patients.
AB  - BACKGROUND/AIMS: The prevalence of diabetes in Korea is reported to be
      approximately 10%, but cases of maturity-onset diabetes of the young (MODY) are
      rare in Korea. A diagnostic technique for autosomal dominant MODY is being
      actively sought. In this regard, we used a DNA chip to investigate the frequency
      of mutations of the MODY3 gene (hepatocyte nuclear factor-1alpha) in Korean
      patients with early-onset type 2 diabetes. METHODS: The genomic DNA of 30 normal
      individuals [age, 24.9+/-8.6 years] and 25 patients with early-onset type 2
      diabetes (age, 27+/-5.9 years) was extracted, and the MODY3 gene was amplified.
      The amplified DNA was hybridized onto a MODY3 chip, which has oligonucleotides of
      15-25 bases, representing wild-type and mutant MODY3 sequences in both forward
      and reverse orientations, immobilized on its surface. RESULTS: Among the normal
      subjects, there was no mutation of MODY3. Among those with early-onset type 2
      diabetes, there was one case of MODY3 mutation. CONCLUSIONS: Our results indicate
      that MODY3 mutations are not rare in Korean early-onset type 2 diabetes patients
      in Korea and suggest that MODY3 mutations in patients with early-onset type 2
      diabetes need to be further evaluated.

PMID- 19119253
TI  - Factors for poor prognosis of near-fatal asthma after recovery from a life
      threatening asthma attack.
AB  - BACKGROUND/AIMS: The aim of this study was to investigate poor prognostic factors
      associated with a near-fatal asthma attack following patient recovery. METHODS:
      We enrolled 68 patients who suffered near-fatal asthma attacks and were admitted
      to the intensive care units of five university hospitals. The patients were
      divided into two groups. The first group was comprised of patients who
      discontinued oral corticosteroids within 6 months after being discharged from the
      hospital and who maintained a forced expiratory volume in 1 s (FEV(1)) >/=60% of
      the maximum or estimated values of the corresponding patients. The second group
      included patients who continued on oral corticosteroids for >/=6 months or who
      maintained a FEV(1) <60%. RESULTS: In patients with near-fatal asthma, factors
      for a poor prognosis included older age [48.47+/-3.53 vs. 64.69+/-2.59 years,
      p<0.05], chronic severe asthma, high values for inflammation-related laboratory
      markers (ESR, 8.75+/-2.05 vs. 23.88+/-4.40 mm/h, p=0.004; CRP, 1.72+/-0.46 vs.
      6.68+/-9.36 mg/dL, p<0.05), asthma exacerbated by pneumonia (28.1 vs. 52.8%,
      p<0.05), and relatively low nutritional status (albumin, 4.00+/-0.14 vs. 3.51+/
      0.10 g/dL, p<0.05). CONCLUSIONS: These prognostic factors may induce irreversible
      obstruction of the airways with subsequent acute exacerbation of asthma or the
      need for continual oral corticosteroids after being discharged from the hospital.
      Patients with these factors should be treated appropriately, under close
      surveillance.

PMID- 19119254
TI  - Effects of dehydroepiandrosterone on Th2 cytokine production in peripheral blood
      mononuclear cells from asthmatics.
AB  - BACKGROUND/AIMS: The androgen dehydroepiandrosterone (DHEA) attenuates allergic
      inflammatory airway reactions by down-regulating the Th2 response in mice. The
      purpose of this study was to investigate whether DHEA suppresses Th2 cytokine
      production in cultured peripheral blood mononuclear cells (PBMCs) from asthmatic
      patients. METHODS: Sixty-one consecutive suspected asthmatic or non-asthmatic men
      underwent tests for asthma. PBMCs from each subject were cultured with and
      without DHEA (0.01~10 microM) for 48 h. The concentrations of interferon (IFN)
      gamma, interleukin (IL)-5, and IL-10 in the culture supernatant were measured via
      an enzyme-linked immunosorbent assay. RESULTS: In PBMCs from subjects exhibiting
      methacholine airway hyperresponsiveness (AHR), DHEA significantly suppressed IL
      10, IL-5, and IFN-gamma production in a dose-dependent manner (all p<0.001) and
      tended to increase the IFN-gamma/IL-5 ratio (p=0.087). DHEA (10 microM)
      suppressed cytokine production to a greater degree in subjects with AHR compared
      with those without AHR (IL-5: 24.0+/-7.8% vs. 40.9+/-3.6%, p<0.01; IFN-gamma:
      29.7+/-7.0% vs. 54.5+/-5.1%, p<0.01). Cytokine suppression was significantly
      related to AHR, serum total IgE levels, and skin reactivity to house dust mites.
      CONCLUSIONS: DHEA suppressed both Th1 and Th2 responses, with a Th1 bias, and the
      degree of suppression was associated with the severity of AHR or atopy.
      Therefore, DHEA may be a useful therapy for asthma.

PMID- 19119255
TI  - Autologous stem cell transplantation for diffuse large B-cell lymphoma with
      residual extranodal involvement.
AB  - BACKGROUND/AIMS: Diffuse large B-cell lymphoma (DLBCL) in Koreans is frequently
      accompanied by extranodal (EN) disease at the time of autologous stem cell
      transplantation (ASCT). We sought to determine whether high EN involvement
      affected survival following ASCT in Koreans. METHODS: We reviewed 27 patients who
      had DLBCL with residual disease at ASCT: 13 with residual disease at nodal
      site(s) only and 14 with nodal and EN disease. RESULTS: Univariate analysis
      showed that disease status, lactate dehydrogenase (LDH), and performance status
      at ASCT were predictors of survival following ASCT. The number of EN sites, as
      categorized by the International Prognostic Index system, had no prognostic
      significance. When EN involvement at ASCT was classified as negative or positive,
      the 2-year overall survival for the negative group was 64%, significantly better
      than the 14% for the positive group (p=0.021), and the event-free survival for
      the negative group was 62%, significantly better than the 14% for the positive
      group (p=0.02). CONCLUSIONS: Patients who had DLBCL with residual EN involvement
      at ASCT showed worse outcomes following ASCT compared to those without EN
      disease.

PMID- 19119256
TI  - Relationship between serum brain natriuretic peptide and heart function in
      patients with chronic kidney disease.
AB  - BACKGROUND/AIMS: Brain natriuretic peptide (BNP) levels are known to be elevated
      in patients with chronic kidney disease (CKD) and normal heart function.
      Therefore, the present study was performed to examine the effectiveness of BNP
      level in diagnosing heart failure in patients with CKD and to determine its
      effects on survival rate and prognosis. METHODS: A total of 182 patients with CKD
      who visited the hospital due to dyspnea of NYHA class II were included in the
      study. BNP levels were measured and echocardiography was performed to divide the
      subjects into groups with and without heart failure. Their BNP levels, clinical
      courses, and survival rates were analyzed retrospectively. RESULTS: When BNP
      level was >/=858.5 pg/mL in CKD patients, heart failure could be diagnosed with
      sensitivity and specificity of 77% and 72%, respectively. Survival rate of the
      group with BNP levels of >/=858.8 pg/mL was significantly lower than that of the
      group with BNP level below this threshold (p=0.012) and multivariate analysis
      showed that BNP level, age, and sex affected survival rate in the group with BNP
      level >/=858.8 pg/mL. CONCLUSIONS: BNP levels of patients with CKD showed a
      positive correlation with creatinine levels, and the critical point of BNP level
      for diagnosis of heart failure was 858.5 pg/mL. As the survival rate in patients
      with BNP level above the critical point was significantly low, this level was a
      useful indicator for predicting their prognosis. Care should be taken in
      interpreting BNP level because patients with stage 5 CKD may show a high
      concentration of BNP without heart failure.

PMID- 19119258
TI  - A case of blue rubber bleb nevus syndrome.
AB  - Blue rubber bleb nevus syndrome is a rare disorder that is characterized by
      multiple recurrent vascular malformations, such as hemangioma, and these
      primarily involve the skin and the gastrointestinal tract. It may also involve
      the brain, liver, lungs, and skeletal muscles. A 14-year-old female visited our
      hospital with a chief complaint of dizziness; upon examination, we found multiple
      recurrent hemangiomas on the skin and gastrointestinal tract. We were able to
      diagnose her as suffering from blue rubber bleb nevus syndrome and we treated her
      with methylprednisolone (2 mg/kg/day for 1 month and 1 mg/kg/day for additional 3
      months). We report on this case along with a review of the literature.

PMID- 19119257
TI  - Polymorphism in the promoter region of the klotho gene (G-395A) is associated
      with early dysfunction in vascular access in hemodialysis patients.
AB  - BACKGROUND/AIMS: Vascular access dysfunction is an important cause of morbidity
      and mortality in hemodialysis (HD) patients. Recent studies have shown that a
      klotho gene mutation is related to endothelial dysfunction, thrombosis, and
      arteriosclerosis, which are regarded as causes of vascular access dysfunction. We
      investigated the relationship between the klotho G-395A polymorphism and early
      dysfunction in vascular access in HD patients. METHODS: Patients who underwent
      vascular access operations between 1999 and 2002 were enrolled (n=126).
      Genotyping was performed by allelic discrimination using a 5'-nuclease polymerase
      chain reaction assay. Clinical data that could be relevant to access dysfunction
      were obtained from medical records. Early dysfunction of vascular access was
      defined as the need for any angioplastic or surgical intervention to correct or
      replace a poorly or nonfunctioning vascular access within 1 year and at least 8
      weeks after initial access placement. RESULTS: Of the 126 patients, the genotype
      frequency of G-395A was 72.2% for GG (n=91), 24.6% for GA (n=31), and 3.2% for AA
      (n=4), and the frequency of minor allele was 0.155. Clinical data were similar
      between the two groups, divided according to the status of the A allele. Early
      dysfunction occurred in 34 (27.0%) of patients, but it occurred at a
      significantly higher rate in A allele carriers (45.7%, 16/35) than in noncarriers
      (19.8%, 18/91; p=0.003). CONCLUSIONS: Our results suggest that the klotho G-395A
      polymorphism could be a risk factor for early dysfunction of vascular access in
      HD patients.

PMID- 19119259
TI  - A case of scar sarcoidosis.
AB  - Infiltration of sarcoid granuloma in old cutaneous scars is one of the uncommon
      cutaneous manifestations of sarcoidosis. Here, we report the case of a 47-year
      old female who presented with swelling and irritation in 5 old scars. She had
      acquired these scars 9 years ago in a traffic accident. An incisional scar biopsy
      revealed noncaseating granulomas consistent with sarcoidosis. High-resolution CT
      (HRCT) revealed right paratracheal, both hilar, paraaortic, and subcarinal
      lymphadenopathy without any nodular densities in both lung fields. Successful
      regression of cutaneous inflammation was achieved using a short course of oral
      steroids.

PMID- 19119260
TI  - A case of congenital bilateral coronary-to-right ventricle fistula coexisting
      with variant angina.
AB  - A coronary arteriovenous (AV) fistula consists of a communication between a
      coronary artery and a cardiac chamber, a great artery or the vena cava. It is the
      most common anomaly that can affect coronary perfusion. Yet bilateral involvement
      of a coronary fistula, constitutes an uncommon subgroup of coronary AV fistulas.
      We herein report on a case of bilateral coronary AV fistula that was coexistent
      with variant angina originating from the distal right ventricular branch of the
      right coronary artery and the distal septal branch of the left anterior
      descending artery, and the latter drained into the right ventricle.

PMID- 19119261
TI  - A case of granulomatous lung disease in a patient with Good's syndrome.
AB  - Good's syndrome is extremely rare. This adult-onset condition is characterized by
      a thymoma with immunodeficiency, low B- and T-cell counts, and hypo
      gammaglobulinemia. The initial clinical presentation is either a mass-lesion
      thymoma or a recurrent infection. Patients with Good's syndrome are very
      susceptible to infections; common respiratory and opportunistic infections can be
      life-threatening. There are no reports of granulomatous lung disease in patients
      with Good's syndrome, although it has been observed in patients with common
      variable immunodeficiency, of which Good's syndrome is a subset. We describe a 53
      year-old male thymoma patient who presented with respiratory symptoms caused by
      granulomatous lung disease and an opportunistic infection. He died of
      uncontrolled fungal infection despite repeated intravenous immunoglobulin and
      supportive care. Clinicians should look for evidence of immunologic dysfunction
      in thymoma patients presenting with severe recurrent infections, especially
      opportunistic infections.

PMID- 19119262
TI  - Association of SLC34A2 variation and sodium-lithium countertransport activity in
      humans and baboons.
AB  - BACKGROUND: Sodium-lithium countertransport (SLC) activity, an intermediate
      phenotype of essential hypertension, has been linked to a region of baboon
      chromosome 5, homologous to human chromosome 4p. Human SLC34A2, located at
      chromosome 4p15.1-p15.3, is a positional candidate gene for SLC. The specific aim
      of this study was to identify genetic variants of the SLC34A2 gene in both baboon
      and human, and to examine the relationship of these polymorphisms with SLC
      activity and blood pressure. METHODS: Single-nucleotide polymorphism (SNP) was
      identified by sequencing the SLC34A2 gene in 24 baboon founders and 94 unrelated
      individuals. All tag SNPs in SLC34A2 were genotyped in 1,856 individuals from 252
      pedigrees of mixed European ancestry. Three SNPs in baboon were genotyped in 634
      baboons comprising 11 pedigrees. RESULTS: In human, one SNP (rs12501856) was
      found to be significantly associated with SLC individually, though it did not
      pass multiple testing correction; however, haplotype 2 containing allele C of SNP
      rs12501856 showed strong evidence of association with SLC (P = 0.0037) after
      multiple comparison adjustment. This haplotype was also marginally associated
      with diastolic blood pressure and systolic blood pressure. This finding was
      confirmed in baboons, where a highly significant association was detected between
      SLC and baboon SNP Asn136Asn (P = 0.0001). However, the associated SNP did not
      account for the linkage signal on baboon chromosome 5. CONCLUSIONS: Consistent
      results in two different species imply that SLC34A2 is associated with SLC
      activity and blood pressure.

PMID- 19119263
TI  - G-protein-coupled receptor kinase 4 polymorphisms and blood pressure response to
      metoprolol among African Americans: sex-specificity and interactions.
AB  - BACKGROUND: African Americans have a disproportionate burden of hypertension and
      comorbid disease. Pharmacogenetic markers of blood pressure response have yet to
      be defined clearly. This study explores the association between G-protein-coupled
      receptor kinase type 4 (GRK4) variants and blood pressure response to metoprolol
      among African Americans with early hypertensive nephrosclerosis. METHODS:
      Participants from the African American Study of Kidney Disease and Hypertension
      (AASK) trial were genotyped at three GRK4 polymorphisms: R65L, A142V, and A486V.
      A Cox proportional hazards model, stratified by gender, was used to determine the
      relationship between GRK4 variants and time to reach a mean arterial pressure
      (MAP) of 107 mm Hg, adjusted for other predictors of blood pressure response.
      Potential interactions between the three polymorphisms were explored by analyzing
      the effects of gene haplotypes and by stratifying the analysis by neighboring
      sites. RESULTS: The hazard ratio with 95% confidence interval by A142V among men
      randomized to a usual MAP (102-107 mm Hg) was 1.54 (1.11-2.44; P = 0.0009). The
      hazard ratio by A142V with R65/L65 or L65/L65 was 2.14 (1.35-3.39; P = 0.001).
      Haplotype analyses were consistent but inconclusive. There was no association
      between A142V and blood pressure response among women. CONCLUSIONS: Results
      suggest a sex-specific relationship between GRK4 A142V and blood pressure
      response among African-American men with early hypertensive nephrosclerosis. Men
      with a GRK4 A142 were less responsive to metoprolol if they had a GRK4 L65
      variant. The effect of GRK4 variants and blood pressure response to metoprolol
      should be studied in larger clinical trials.

PMID- 19119265
TI  - Decanalization and the origin of complex disease.
AB  - Complex genetic disease is caused by the interaction between genetic and
      environmental variables and is the predominant cause of mortality globally.
      Recognition that susceptibility arises through the combination of multiple
      genetic pathways that influence liability factors in a nonlinear manner suggests
      that a process of 'decanalization' contributes to the epidemic nature of common
      genetic diseases. The rapid evolution of the human genome combined with marked
      environmental and cultural perturbation in the past two generations might lead to
      the uncovering of cryptic genetic variation that is a major source of disease
      susceptibility.

PMID- 19119264
TI  - Fundamental concepts in genetics: genetics and the understanding of selection.
AB  - At first sight selection is a simple notion, and some consider it the most
      important evolutionary force. But how important is selection, is it really so
      trivial to understand and what are the alternatives? Here I discuss how genetics
      is crucial for addressing all of these questions: genetics allowed the concept of
      natural selection to become viable, it contributed to our understanding of the
      complexities of selection and it spurred the development of competing models of
      evolution. Understanding how and why selection acts has important potential
      applications, from understanding the mechanisms of disease and microbial
      resistance, to improving the design of transgenes and drugs.

PMID- 19119266
TI  - The other nanotech.

PMID- 19119267
TI  - How spintronics went from the lab to the iPod.

PMID- 19119268
TI  - From two cultures to new cultures.

PMID- 19119269
TI  - A new approach to intellectual property.

PMID- 19119272
TI  - Molecular self-assembly: helping themselves.

PMID- 19119273
TI  - Nanoparticles: designer labels for virus coats.

PMID- 19119274
TI  - Quantum dots: putting the squeeze on nanocrystals.

PMID- 19119275
TI  - Nanowires: bringing order to twin-plane defects.

PMID- 19119277
TI  - Enzyme-assisted self-assembly under thermodynamic control.
AB  - The production of functional molecular architectures through self-assembly is
      commonplace in biology, but despite advances, it is still a major challenge to
      achieve similar complexity in the laboratory. Self-assembled structures that are
      reproducible and virtually defect free are of interest for applications in three
      dimensional cell culture, templating, biosensing and supramolecular electronics.
      Here, we report the use of reversible enzyme-catalysed reactions to drive self
      assembly. In this approach, the self-assembly of aromatic short peptide
      derivatives provides a driving force that enables a protease enzyme to produce
      building blocks in a reversible and spatially confined manner. We demonstrate
      that this system combines three features: (i) self-correction--fully reversible
      self-assembly under thermodynamic control; (ii) component-selection--the ability
      to amplify the most stable molecular self-assembly structures in dynamic
      combinatorial libraries; and (iii) spatiotemporal confinement of nucleation and
      structure growth. Enzyme-assisted self-assembly therefore provides control in
      bottom-up fabrication of nanomaterials that could ultimately lead to functional
      nanostructures with enhanced complexities and fewer defects.

PMID- 19119278
TI  - High-throughput solution processing of large-scale graphene.
AB  - The electronic properties of graphene, such as high charge carrier concentrations
      and mobilities, make it a promising candidate for next-generation nanoelectronic
      devices. In particular, electrons and holes can undergo ballistic transport on
      the sub-micrometre scale in graphene and do not suffer from the scale limitations
      of current MOSFET technologies. However, it is still difficult to produce single
      layer samples of graphene and bulk processing has not yet been achieved, despite
      strenuous efforts to develop a scalable production method. Here, we report a
      versatile solution-based process for the large-scale production of single-layer
      chemically converted graphene over the entire area of a silicon/SiO(2) wafer. By
      dispersing graphite oxide paper in pure hydrazine we were able to remove oxygen
      functionalities and restore the planar geometry of the single sheets. The
      chemically converted graphene sheets that were produced have the largest area
      reported to date (up to 20 x 40 microm), making them far easier to process. Field
      effect devices have been fabricated by conventional photolithography, displaying
      currents that are three orders of magnitude higher than previously reported for
      chemically produced graphene. The size of these sheets enables a wide range of
      characterization techniques, including optical microscopy, scanning electron
      microscopy and atomic force microscopy, to be performed on the same specimen.

PMID- 19119279
TI  - Gram-scale production of graphene based on solvothermal synthesis and sonication.
AB  - Carbon nanostructures have emerged as likely candidates for a wide range of
      applications, driving research into novel synthetic techniques to produce
      nanotubes, graphene and other carbon-based materials. Single sheets of pristine
      graphene have been isolated from bulk graphite in small amounts by
      micromechanical cleavage, and larger amounts of chemically modified graphene
      sheets have been produced by a number of approaches. Both of these techniques
      make use of highly oriented pyrolitic graphite as a starting material and involve
      labour-intensive preparations. Here, we report the direct chemical synthesis of
      carbon nanosheets in gram-scale quantities in a bottom-up approach based on the
      common laboratory reagents ethanol and sodium, which are reacted to give an
      intermediate solid that is then pyrolized, yielding a fused array of graphene
      sheets that are dispersed by mild sonication. The ability to produce bulk
      graphene samples from non-graphitic precursors with a scalable, low-cost approach
      should take us a step closer to real-world applications of graphene.

PMID- 19119280
TI  - Power generation with laterally packaged piezoelectric fine wires.
AB  - Converting mechanical energy into electricity could have applications in sensing,
      medical science, defence technology and personal electronics, and the ability of
      nanowires to 'scavenge' energy from ambient and environmental sources could prove
      useful for powering nanodevices. Previously reported nanowire generators were
      based on vertically aligned piezoelectric nanowires that were attached to a
      substrate at one end and free to move at the other. However, there were problems
      with the output stability, mechanical robustness, lifetime and environmental
      adaptability of such devices. Here we report a flexible power generator that is
      based on cyclic stretching-releasing of a piezoelectric fine wire that is firmly
      attached to metal electrodes at both ends, is packaged on a flexible substrate,
      and does not involve sliding contacts. Repeatedly stretching and releasing a
      single wire with a strain of 0.05-0.1% creates an oscillating output voltage of
      up to approximately 50 mV, and the energy conversion efficiency of the wire can
      be as high as 6.8%.

PMID- 19119281
TI  - Fast, sensitive and spectrally tuneable colloidal-quantum-dot photodetectors.
AB  - Solution-processed semiconductors are compatible with a range of substrates,
      which enables their direct integration with organic circuits, microfluidics,
      optical circuitry and commercial microelectronics. Ultrasensitive photodetectors
      based on solution-process colloidal quantum dots operating in both the visible
      and infrared have been demonstrated, but these devices have poor response times
      (on the scale of seconds) to changes in illumination, and rapid-response devices
      based on a photodiode architecture suffer from low sensitivity. Here, we show
      that the temporal response of these devices is determined by two components-
      electron drift, which is a fast process, and electron diffusion, which is a slow
      process. By building devices that exclude the diffusion component, we are able to
      demonstrate a >1,000-fold improvement in the sensitivity-bandwidth product of
      tuneable colloidal-quantum-dot photodiodes operating in the visible and infrared.

PMID- 19119282
TI  - Optically monitoring the mechanical assembly of single molecules.
AB  - Bottom-up assembly at the level of individual molecules requires a combination of
      utmost spatial precision and efficient monitoring. We have previously shown how
      to 'cut-and-paste' single molecules, and other groups have demonstrated that it
      is possible to beat the diffraction limit in optical microscopy. Here we show
      that a combination of single-molecule cut-and-paste surface assembly, total
      internal reflection fluorescence microscopy and atomic force microscopy can be
      used to deposit individual fluorophores in well-defined nanoscale patterns and
      also to monitor the process in real time with nanometre precision. Although the
      size of the pattern is well below the optical resolution of the microscope, the
      individual dyes are identified by localizing the centroids and detecting the
      photobleaching of the fluorophores. With this combination of methods, individual
      dyes or labelled biomolecules can be arranged at will for specific functions,
      such as coupled fluorophore systems or tailored enzyme cascades, and monitored
      with nanoscale precision.

PMID- 19119283
TI  - Controlled polytypic and twin-plane superlattices in iii-v nanowires.
AB  - Semiconductor nanowires show promise for use in nanoelectronics, fundamental
      electron transport studies, quantum optics and biological sensing. Such
      applications require a high degree of nanowire growth control, right down to the
      atomic level. However, many binary semiconductor nanowires exhibit a high density
      of randomly distributed twin defects and stacking faults, which results in an
      uncontrolled, or polytypic, crystal structure. Here, we demonstrate full control
      of the crystal structure of InAs nanowires by varying nanowire diameter and
      growth temperature. By selectively tuning the crystal structure, we fabricate
      highly reproducible polytypic and twin-plane superlattices within single
      nanowires. In addition to reducing defect densities, this level of control could
      lead to bandgap engineering and novel electronic behaviour.

PMID- 19119285
TI  - Processing and properties of highly enriched double-wall carbon nanotubes.
AB  - Carbon nanotubes consist of one or more concentric graphene cylinders and are
      under investigation for a variety of applications that make use of their
      excellent thermal, mechanical, electronic and optical properties. Double-wall
      nanotubes are ideal systems for studying the interwall interactions influencing
      the properties of nanotubes with two or more walls. However, current techniques
      to synthesize double-wall nanotubes produce unwanted single- and multiwall
      nanotubes. Here, we show how density gradient ultracentrifugation can be used to
      separate double-wall nanotubes from mixtures of single- and multiwall nanotubes
      through differences in their buoyant density. This technique results in samples
      that are highly enriched in either single- or double-wall nanotubes of similar
      outer wall diameter, with the double-wall nanotubes being, on average,
      approximately 44% longer than the single-wall nanotubes. The longer average
      length of the double-wall nanotubes provides distinct advantages when they are
      used in transparent conductors.

PMID- 19119284
TI  - Tuning the optical and electronic properties of colloidal nanocrystals by lattice
      strain.
AB  - Strain can have a large influence on the properties of materials at the
      nanoscale. The effect of lattice strain on semiconductor devices has been widely
      studied, but its influence on colloidal semiconductor nanocrystals is still
      poorly understood. Here we show that the epitaxial deposition of a compressive
      shell (ZnS, ZnSe, ZnTe, CdS or CdSe) onto a soft nanocrystalline core (CdTe) to
      form a lattice-mismatched quantum dot can dramatically change the conduction and
      valence band energies of both the core and the shell. In particular, standard
      type-I quantum-dot behaviour is replaced by type-II behaviour, which is
      characterized by spatial separation of electrons and holes, extended excited
      state lifetimes and giant spectral shifts. Moreover, the strain induced by the
      lattice mismatch can be used to tune the light emission--which displays narrow
      linewidths and high quantum yields--across the visible and near-infrared part of
      the spectrum (500-1,050 nm). Lattice-mismatched core-shell quantum dots are
      expected to have applications in solar energy conversion, multicolour biomedical
      imaging and super-resolution optical microscopy.

PMID- 19119286
TI  - A preliminary model of work during initial examination and treatment planning
      appointments.
AB  - Objective This study's objective was to formally describe the work process for
      charting and treatment planning in general dental practice to inform the design
      of a new clinical computing environment.Methods Using a process called contextual
      inquiry, researchers observed 23 comprehensive examination and treatment planning
      sessions during 14 visits to 12 general US dental offices. For each visit, field
      notes were analysed and reformulated as formalised models. Subsequently, each
      model type was consolidated across all offices and visits. Interruptions to the
      workflow, called breakdowns, were identified.Results Clinical work during dental
      examination and treatment planning appointments is a highly collaborative
      activity involving dentists, hygienists and assistants. Personnel with multiple
      overlapping roles complete complex multi-step tasks supported by a large and
      varied collection of equipment, artifacts and technology. Most of the breakdowns
      were related to technology which interrupted the workflow, caused rework and
      increased the number of steps in work processes.Conclusion Current dental
      software could be significantly improved with regard to its support for
      communication and collaboration, workflow, information design and presentation,
      information content, and data entry.

PMID- 19119288
TI  - [Faster, better, stronger].

PMID- 19119287
TI  - Factors other than glomerular filtration rate affect serum cystatin C levels.
AB  - Cystatin C is an endogenous glomerular filtration marker hence its serum level is
      affected by the glomerular filtration rate (GFR). To study what other factors
      might affect it blood level we performed a cross-sectional analysis of 3418
      patients which included a pooled dataset of clinical trial participants and a
      clinical population with chronic kidney disease. The serum cystatin C and
      creatinine levels were related to clinical and biochemical parameters and errors
      in-variables models were used to account for errors in GFR measurements. The GFR
      was measured as the urinary clearance of 125I-iothalamate and 51Cr-EDTA. Cystatin
      C was determined at a single laboratory while creatinine was standardized to
      reference methods and these were 2.1+/-1.1 mg/dL and 1.8+/-0.8 mg/L,
      respectively. After adjustment for GFR, cystatin C was 4.3% lower for every 20
      years of age, 9.2% lower for female gender but only 1.9% lower in blacks.
      Diabetes was associated with 8.5% higher levels of cystatin C and 3.9% lower
      levels of creatinine. Higher C-reactive protein and white blood cell count and
      lower serum albumin were associated with higher levels of cystatin C and lower
      levels of creatinine. Adjustment for age, gender and race had a greater effect on
      the association of factors with creatinine than cystatin C. Hence, we found that
      cystatin C is affected by factors other than GFR which should be considered when
      the GFR is estimated using serum levels of cystatin C.

PMID- 19119289
TI  - [Obesity epidemics--we must start with the children].

PMID- 19119290
TI  - [The development of BMI in 4-year-olds in Tromso 1980 to 2005].
AB  - BACKGROUND: Studies indicate that the number of overweight adults and children in
      Norway is increasing. The aim of this study was to find out whether the epidemic
      of obesity has reached 4-year olds in Tromso. MATERIAL AND METHOD: The study is
      retrospective and compares cross-sectional surveys to find trends. Age in months,
      height and weight of 4-year olds were collected from child health care centre
      records in Tromso, Norway. Data from 1645 children born in 1976, 1981, 1986, 1991
      and 2001 were collected. The body mass index (BMI) was calculated and adjusted
      for age with standard deviation scores. The children were classified as normal or
      overweight based on the recommendations from the International Obesity Task
      Force. RESULTS: Mean BMI was 15.9 kg/m2 for boys and 15.8 kg/m2 for girls born in
      2001. BMI had not changed significantly from that for children born in 1976. The
      prevalence of overweight in girls has increased significantly from 7.2 % to 16.8
      % in the same period (p = 0.02). The prevalence of overweight in boys born in
      2001 was 8.8 %; this is not significantly different from those born in 1976. At
      the two most recent measurements the prevalence of overweight in girls was
      significantly higher than the prevalence of overweight in boys. INTERPRETATION:
      The increasing prevalence of overweight in girls may indicate that the epidemic
      of obesity is starting to affect 4-year-old girls in Tromso. The development is
      worrying and should be further monitored and followed up.

PMID- 19119291
TI  - [High-cost medicine--do we lack open and legitimate procedures for
      prioritising?].
AB  - BACKGROUND: The gap between health needs and available resources leads to daily
      rationing decisions within the health system. We have explored whether procedures
      exist that can promote legitimate priority decisions in connection with
      implementation of new and expensive technology; implementation of new treatment
      regimes for colorectal cancer and breast cancer in Norway in 2005 are used as
      examples. MATERIAL AND METHODS: This is a qualitative case study. The theoretical
      framework: "Accountability for reasonableness" was used to evaluate the
      introduction of the cancer drugs cetuximab (Erbitux) and trastuzumab (Herceptin).
      Data sources were official documents, newspaper articles and scientific
      publications with relevance to the priority setting debate concerning cetuximab
      and trastuzumab. RESULTS: Both cases illustrate hard choices with reasonable
      disagreements about values and data interpretation. The cases illustrate lack of
      publicity of both the decisions and their rationales. Cetuximab is less effective
      and costs more than trastuzumab. Weighting of cost and effect varied between the
      decision-makers. There are no formal mechanisms for appeals for patients who
      don't get the treatment they feel they are entitled to. INTERPRETATION: When
      these two priority cases were debated there were no established institutions or
      implemented procedures to facilitate an open and explicit priority setting
      procedure taking into consideration reasonable disagreement on substantive
      values.

PMID- 19119292
TI  - [Nuclear medicine examination in heart failure patients].
AB  - BACKGROUND: Recently, cardiac resynchronization therapy, by using biventricular
      pacemakers, has become implemented in the treatment of patients with severe heart
      failure. However, using the classical inclusion criteria, 30 % of patients
      treated with resynchronization do not improve symptoms or activity level. Phase
      analysis of radionuclide ventriculography gives information about pattern of
      ventricular contraction and may detect dyssynchrony. The method may therefore be
      used to select patients with dyssynctrony to resynchronization therapy. In this
      study we have investigated the amount of dyssynchrony, by using phase analysis of
      radionuclide ventriculography, in men and women as a function of left ventricular
      ejection fraction. MATERIAL AND METHODS: The study is based on 1 266 radionuclide
      ventriculographies performed at Section of Nuclear Medicine, University Hospital
      North-Norway, during 1998 - 2006. The relationship between left ventricular
      ejection fraction and number of patients with ventricular dyssynchrony was
      investigated. 90 patients with no known heart problems were considered as
      reference values for synchrony data. RESULTS: The phase analysis showed that 35 %
      of the women and 34 % of the men with left ventricular ejection fraction below 35
      % had both inter- and intra-ventricular dyssynchrony. INTERPRETATION: Today's
      criteria for including patients to resynchonizing therapy are not good enough.
      Phase analysis of radionuclide ventriculography of patients with left ventricular
      ejection fraction below 35 % shows that one third of the patients have both inter
      and intra- ventricular dyssynchrony. These patients might be responders to
      resynchronization therapy.

PMID- 19119293
TI  - [Polyunsaturated fatty acids and epilepsy].
AB  - BACKGROUND: 30 % of patients with epilepsy have recurrent drug-resistent
      seizures. Some children with catastrophic epilepsy have responded well to a
      ketogenic diet. Polyunsaturated fatty acids are at least partly responsible for
      the anticonvulsive effect of this diet and could perhaps be used to treat
      epilepsy. MATERIAL AND METHODS: The paper is based on literature (published
      before June 2008) retrieved through a non-systematic search of the Cochrane and
      PubMed databases. The following search words were used: epilepsy, polyunsaturated
      fatty acids, clinical trials, ketogen diet, and treatment. Articles focusing on
      clinical aspects were selected. RESULTS AND INTERPRETATION: Articles on clinical
      studies and laboratory research were retrieved from Pubmed, while studies on
      ketogen diet were retrieved from Cochrane. Animal studies show that increased
      intake of polyunsaturated fatty acids can reduce the likelihood of epileptic
      seizures through various biochemical mechanisms. However, there is not sufficient
      evidence to conclude that polyunsaturated fatty acids have antiepileptic effects
      in people with epilepsy. More research is needed before polyunsaturated fatty
      acids can be presented as a treatment option for epilepsy.

PMID- 19119294
TI  - [Portal vein embolization before surgery for liver tumours].
AB  - BACKGROUND: Radical resection is the only long-term cure for malignant liver
      tumours. An important contraindication for surgery is that the liver remnant
      would be too small. Embolization of the portal vein in the tumour-bearing side of
      the liver may induce growth of the healthy part and thereby render liver
      resection possible. MATERIAL AND METHODS: 18 patients, aged 35 - 71 years,
      underwent portal vein embolization in the period 2002 - 2006. An interventional
      radiological percutaneous transhepatic technique was used. RESULTS: The liver
      remnant increased with 45 % (median), range 9 - 100 %, in all patients. Liver
      resection could be done and was performed in 10 patients. Due to tumour
      progression, resection could not be done in seven patients. One patient was
      excluded from surgery due to serious side effects of chemotherapy. Four-year
      survival for patients with metastases from colorectal cancer (n=9) was 58 %.
      INTERPRETATION: Portal vein embolization results in a substantial increase of
      liver volume. The technique effectively increases the number of patients eligible
      for liver surgery. It is possible for patients treated with this technique to
      obtain the same long-term survival as those primarily regarded to be operable.
      Advanced radiological technology is needed to exclude patients who would not
      profit from the procedure.

PMID- 19119295
TI  - [Drug testing in hair].

PMID- 19119296
TI  - [Do we need the superego?].

PMID- 19119297
TI  - [National incident reporting system also for the Norwegian health care].

PMID- 19119298
TI  - [Does the Radium Hospital have a tobacco policy?].

PMID- 19119299
TI  - [Self-help groups are effective].

PMID- 19119301
TI  - [When the Medical Association fails].

PMID- 19119303
TI  - [Obama's health plan].

PMID- 19119306
TI  - Confirmatory factor analysis of the Short Form McGill Pain Questionnaire with
      burn patients.
AB  - The Short Form McGill Pain Questionnaire (SF-MPQ) is an abbreviated version of
      McGill Pain Questionnaire (MPQ) developed for pragmatic reasons to improve the
      clinical utility of the MPQ. Although the SF-MPQ has been used in more than 250
      published studies, few studies have examined the core constructs it measures. The
      objective of this study was to evaluate in a sample with burn injuries whether
      the factor structure of the SF-MPQ is consistent with the theoretic pain
      constructs it purports to measure. Participants (n = 338) met American Burn
      Association's criteria for major burn injury and had a mean total body surface
      area burned of 14%. They were mostly male (70.1%) and Caucasian (63.4%) with an
      average age of 41.25 years. There were 2 primary findings. First, confirmatory
      factor analysis yielded fit index values demonstrating viability of a 2-factor,
      oblique, solution composed of sensory and affective latent constructs. These
      findings were consistent with previous work and the theoretic constructs. Second,
      results from a relatively new model consisting of 8 SF-MPQ items demonstrated
      potential viability for measuring similar constructs.

PMID- 19119307
TI  - Evaluation of fractional analysis of bronchoalveolar lavage combined with
      cellular morphological features.
AB  - BACKGROUND: The value of bronchoalveolar lavage (BAL) still remains
      controversial, prompting a need for further improvement. The purpose of this
      study was to develop and evaluate a sequential analysis of cell content in
      fractional BAL (FBAL) from the airways and alveolar sacs with incorporation of
      the cellular morphologic features. METHODS: Initially, 30 ml saline was infused
      into a subsegmental lobe of the lung and the recovered fluid was assigned as FBAL
      I being mainly originated from whole airways. The second and third lavages (FBAL
      II and FBAL-III) each were performed using 50 ml saline being from more distal
      portions of airways and alveolar sacs respectively in the same lobe. Total cell
      number/ml and percentages of macrophages, lymphocytes, neutrophils, and
      eosinophils in each fraction together with their morphological alterations and
      mast cells, basophils and Masson bodies were assessed. RESULTS: In the 12
      controls, percentage of neutrophils was high and lymphocytes and macrophages were
      low in FBAL-I while in FBAL-III, neutrophils decreased to nearly nil and
      lymphocytes and macrophages were increased. Analysis of FBAL from 76 patients
      with sarcoidosis and 14 with hypersensitivity pneumonitis (HP) revealed that a
      predominance of small, round and well-differentiated lymphocytes with relative
      absence of neutrophils, basophils and Masson bodies correlated best with
      sarcoidosis. In contrast, neutrophil predominance and presence of lymphocytes
      having deep nuclear indentations and abundant cytoplasm with a process resembling
      a "hand-mirror" correlated well with HP. CONCLUSIONS: Evaluation of FBAL together
      with cellular morphological features especially characteristics of lymphocytes
      provides valuable information for establishing the diagnosis in interstitial lung
      diseases.

PMID- 19119308
TI  - Genome-wide analysis of BP1 transcriptional targets in breast cancer cell line
      Hs578T.
AB  - Homeobox genes are known to be critically important in tumor development and
      progression. The BP1 (Beta Protein 1) gene, an isoform of DLX4, belongs to the
      Distal-less (DLX) subfamily of homeobox genes and encodes a homeodomain
      containing transcription factor. Our studies have shown that the BP1 gene was
      overexpressed in 81% of primary breast cancer and its expression was closely
      correlated with the progression of breast cancer. However, the exact role of BP1
      in breast has yet to be elucidated. Therefore, it is important to explore the
      potential transcriptional targets of BP1 via whole genome-scale screening. In
      this study, we used the chromatin immunoprecipitation on chip (ChIP-on-chip) and
      gene expression microarray assays to identify candidate target genes and gene
      networks, which are directly regulated by BP1 in ER negative (ER-) breast cancer
      cells. After rigorous bioinformatic and statistical analysis for both ChIP-on
      chip and expression microarray gene lists, 18 overlapping genes were noted and
      verified. Those potential target genes are involved in a variety of tumorigenic
      pathways, which sheds light on the functional mechanisms of BP1 in breast cancer
      development and progression.

PMID- 19119309
TI  - Using profiles based on nucleotide hydrophobicity to define essential regions for
      splicing.
AB  - The splice-site sequences of U2-type introns are highly degenerate, so many
      different sequences can function as U2-type splice sites. Using our new profiles
      based on hydrophobicity properties we pointed out specific properties for regions
      surrounding splice sites. We built a set T of flanking regions of genes with 1-3
      introns from 21st and 22nd chromosomes extracted from GenBank to define positions
      having conserved properties, namely hydrophobicity, that are potentially
      essential for recognition by spliceosome. GT-AG introns exist in U2 and U12
      types. Therefore, intron type cannot be simply determined by the dinucleotide
      termini. We attempted to distinguish U2 and U12-types introns with help of
      hydrophobicity profiles on sets of spice sites for U2 or U12-type introns
      extracted from SpliceRack database. The positions given by our method, which may
      be important for recognition by spliceosome, were compared to the nucleotide
      consensus provided by a classical method, Pictogram. We showed that there is a
      similarity of hydrophobicity profiles inside intron types. On one hand, GT-AG and
      GC-AG introns belonging to U2-type have resembling hydrophobicity profiles as
      well as AT-AC and GT-AG introns belonging to U12-type. On the other hand,
      hydrophobicity profiles of U2 and U12-types GT-AG introns are completely
      different. We suggest that hydrophobicity profiles facilitate definition of
      intron type, distinguishing U2 and U12 intron types and can be used to build
      programs to search splice site and to evaluate their strength. Therefore, our
      study proves that hydrophobicity profiles are informative method providing
      insights into mechanisms of splice sites recognition.

PMID- 19119310
TI  - Metal A and metal B sites of nuclear RNA polymerases Pol IV and Pol V are
      required for siRNA-dependent DNA methylation and gene silencing.
AB  - Plants are unique among eukaryotes in having five multi-subunit nuclear RNA
      polymerases: the ubiquitous RNA polymerases I, II and III plus two plant-specific
      activities, nuclear RNA polymerases IV and V (previously known as Polymerases IVa
      and IVb). Pol IV and Pol V are not required for viability but play non-redundant
      roles in small interfering RNA (siRNA)-mediated pathways, including a pathway
      that silences retrotransposons and endogenous repeats via siRNA-directed DNA
      methylation. RNA polymerase activity has not been demonstrated for Polymerases IV
      or V in vitro, making it unclear whether they are catalytically active enzymes.
      Their largest and second-largest subunit sequences have diverged considerably
      from Pol I, II and III in the vicinity of the catalytic center, yet retain the
      invariant Metal A and Metal B amino acid motifs that bind magnesium ions
      essential for RNA polymerization. By using site-directed mutagenesis in
      conjunction with in vivo functional assays, we show that the Metal A and Metal B
      motifs of Polymerases IV and V are essential for siRNA production, siRNA-directed
      DNA methylation, retrotransposon silencing, and the punctate nuclear localization
      patterns typical of both polymerases. Collectively, these data show that the
      minimal core sequences of polymerase active sites, the Metal A and B sites, are
      essential for Pol IV and Pol V biological functions, implying that both are
      catalytically active.

PMID- 19119311
TI  - Critical evaluation of branch polarity and apical dominance as dictators of
      colony astogeny in a branching coral.
AB  - The high morphological resemblance between branching corals and trees, can lead
      to comparative studies on pattern formation traits, best exemplified in plants
      and in some cnidarians. Here, 81 branches of similar size of the hermatypic coral
      Stylophora pistillata were lopped of three different genets, their skeletons
      marked with alizarin red-S, and divided haphazardly into three morphometric
      treatment groups: (I) upright position; (II) horizontal position, intact tip; and
      (III) horizontal position, cut tip. After 1 y of in-situ growth, the 45 surviving
      ramets were brought to the laboratory, their tissues removed and their
      architectures analyzed by 22 morphological parameters (MPs). We found that within
      1 y, isolated branches developed into small coral colonies by growing new
      branches from all branch termini, in all directions. No architectural
      dissimilarity was assigned among the three studied genets of treatment I
      colonies. However, a major architectural disparity between treatment I colonies
      and colonies of treatments II and III was documented as the development of mirror
      structures from both sides of treatments II and III settings as compared to tip
      borne architectures in treatment I colonies. We did not observe apical dominance
      since fragments grew equally from all branch sides without documented dominant
      polarity along branch axis. In treatment II colonies, no MP for new branches
      originating either from tips or from branch bases differed significantly. In
      treatment III colonies, growth from the cut tip areas was significantly lower
      compared to the base, again, suggesting lack of apical dominance in this species.
      Changes in branch polarity revealed genet associated plasticity, which in one of
      the studied genets, led to enhanced growth. Different genets exhibited
      canalization flexibility of growth patterns towards either lateral growth, or
      branch axis extension (skeletal weight and not porosity was measured). This study
      revealed that colony astogeny in S. pistillata is a regulated process expressed
      through programmed events and not directly related to simple energy trade-off
      principles or to environmental conditions, and that branch polarity and apical
      dominance do not dictate colony astogeny. Therefore, plasticity and astogenic
      disparities encompass a diversity of genetic (fixed and flexible) induced
      responses.

PMID- 19119312
TI  - BRCA1, hormone, and tissue-specific tumor suppression.
AB  - Germline mutations of BRCA1 predispose women to breast and ovarian cancers.
      Elucidating molecular mechanism of tissue- and gender-specific phenomena in BRCA1
      related tumors is a key to our understanding of BRCA1 function in tumor
      suppression. This review summarizes studies in recent years on the link between
      BRCA1 and estrogen/progesterone signaling pathways, as well as discusses various
      models underscoring a triangle relationship among BRCA1, estrogen and genome
      instability.

PMID- 19119313
TI  - Differential display of expressed genes reveals a novel function of SFRS18 in
      regulation of intramuscular fat deposition.
AB  - Intramuscular fat (IMF) content plays a key role in establishing pork quality. In
      the present study, differential-display reverse transcription-polymerase chain
      reaction (DDRT-PCR) was used to identify differentially expressed (DE) genes
      between longissimus dorsi (LD) muscles with extremely different IMF content. A
      major DE gene associated with IMF content was identified as splicing factor
      serine-arginine rich protein (SFRS18) gene, also known as SRrp130. The gene
      exhibited relatively higher expression levels in LD muscles with higher IMF
      content. A full-length cDNA sequence of pig SFRS18 gene was obtained by in silico
      comparative cloning coupled with PCR target sequencing, while the current EST
      (expressed sequence tag) database supported two transcript variants of the pig
      gene. Differential expression of the SFRS18 gene was further confirmed using
      quantitative PCR. The mRNA levels of SFRS18 gene showed significant and positive
      correlation with IMF content in LD muscle (r = 0.54, P < 0.01). Collectively,
      these results suggest that the SFRS18 gene is involved in the regulation of IMF
      deposition in pig and that it may be a useful tool in selecting animals for
      desired amounts of fatness for high quality pork.

PMID- 19119314
TI  - Aging impairs recipient T cell intrinsic and extrinsic factors in response to
      transplantation.
AB  - BACKGROUND: As increasing numbers of older people are listed for solid organ
      transplantation, there is an urgent need to better understand how aging modifies
      alloimmune responses. Here, we investigated whether aging impairs the ability of
      donor dendritic cells or recipient immunity to prime alloimmune responses to
      organ transplantation. PRINCIPAL FINDINGS: Using murine experimental models, we
      found that aging impaired the host environment to expand and activate antigen
      specific CD8(+) T cells. Additionally, aging impaired the ability of polyclonal T
      cells to induce acute allograft rejection. However, the alloimmune priming
      capability of donor dendritic cells was preserved with aging. CONCLUSION: Aging
      impairs recipient responses, both T cell intrinsic and extrinsic, in response to
      organ transplantation.

PMID- 19119315
TI  - High-resolution analysis of the 5'-end transcriptome using a next generation DNA
      sequencer.
AB  - Massively parallel, tag-based sequencing systems, such as the SOLiD system, hold
      the promise of revolutionizing the study of whole genome gene expression due to
      the number of data points that can be generated in a simple and cost-effective
      manner. We describe the development of a 5'-end transcriptome workflow for the
      SOLiD system and demonstrate the advantages in sensitivity and dynamic range
      offered by this tag-based application over traditional approaches for the study
      of whole genome gene expression. 5'-end transcriptome analysis was used to study
      whole genome gene expression within a colon cancer cell line, HT-29, treated with
      the DNA methyltransferase inhibitor, 5-aza-2'-deoxycytidine (5Aza). More than 20
      million 25-base 5'-end tags were obtained from untreated and 5Aza-treated cells
      and matched to sequences within the human genome. Seventy three percent of the
      mapped unique tags were associated with RefSeq cDNA sequences, corresponding to
      approximately 14,000 different protein-coding genes in this single cell type. The
      level of expression of these genes ranged from 0.02 to 4,704 transcripts per
      cell. The sensitivity of a single sequence run of the SOLiD platform was 100
      1,000 fold greater than that observed from 5'end SAGE data generated from the
      analysis of 70,000 tags obtained by Sanger sequencing. The high-resolution 5'end
      gene expression profiling presented in this study will not only provide novel
      insight into the transcriptional machinery but should also serve as a basis for a
      better understanding of cell biology.

PMID- 19119316
TI  - Temporal and individual variation in offspring provisioning by tree swallows: a
      new method of automated nest attendance monitoring.
AB  - Studies of the ecology and evolution of avian nesting behavior have been limited
      by the difficulty and expense of sampling nest attendance behavior across entire
      days or throughout a substantial portion of the nestling period. Direct
      observation of nesting birds using human observers and most automated devices
      requires sub-sampling of the nestling period, which does not allow for the
      quantification of the duration of chick-feeding by parents within a day, and may
      also inadequately capture temporal variation in the rate at which chicks are fed.
      Here I describe an inexpensive device, the Automated Perch Recorder (APR) system,
      which collects accurate, long-term data on hourly rates of nest visitation, the
      duration of a pair's workday, and the total number of visits the pair makes to
      their nest across the entire period for which it is deployed. I also describe
      methods for verifying the accuracy of the system in the field, and several
      examples of how these data can be used to explore the causes of variation in and
      tradeoffs between the rate at which birds feed their chicks and the total length
      of time birds spend feeding chicks in a day.

PMID- 19119317
TI  - Incomplete inhibition of sphingosine 1-phosphate lyase modulates immune system
      function yet prevents early lethality and non-lymphoid lesions.
AB  - BACKGROUND: S1PL is an aldehyde-lyase that irreversibly cleaves sphingosine 1
      phosphate (S1P) in the terminal step of sphingolipid catabolism. Because S1P
      modulates a wide range of physiological processes, its concentration must be
      tightly regulated within both intracellular and extracellular environments.
      METHODOLOGY: In order to better understand the function of S1PL in this
      regulatory pathway, we assessed the in vivo effects of different levels of S1PL
      activity using knockout (KO) and humanized mouse models. PRINCIPAL FINDINGS: Our
      analysis showed that all S1PL-deficient genetic models in this study displayed
      lymphopenia, with sequestration of mature T cells in the thymus and lymph nodes.
      In addition to the lymphoid phenotypes, S1PL KO mice (S1PL(-/-)) also developed
      myeloid cell hyperplasia and significant lesions in the lung, heart, urinary
      tract, and bone, and had a markedly reduced life span. The humanized knock-in
      mice harboring one allele (S1PL(H/-)) or two alleles (S1PL(H/H)) of human S1PL
      expressed less than 10 and 20% of normal S1PL activity, respectively. This
      partial restoration of S1PL activity was sufficient to fully protect both
      humanized mouse lines from the lethal non-lymphoid lesions that developed in
      S1PL(-/-) mice, but failed to restore normal T-cell development and trafficking.
      Detailed analysis of T-cell compartments indicated that complete absence of S1PL
      affected both maturation/development and egress of mature T cells from the
      thymus, whereas low level S1PL activity affected T-cell egress more than
      differentiation. SIGNIFICANCE: These findings demonstrate that lymphocyte
      trafficking is particularly sensitive to variations in S1PL activity and suggest
      that there is a window in which partial inhibition of S1PL could produce
      therapeutic levels of immunosuppression without causing clinically significant
      S1P-related lesions in non-lymphoid target organs.

PMID- 19119319
TI  - Nematode homologue of PQBP1, a mental retardation causative gene, is involved in
      lipid metabolism.
AB  - BACKGROUND: PQBP1 is a causative gene for X-linked mental retardation (MR) whose
      patients frequently show lean body. C. elegans has a strictly conserved homologue
      gene of PQBP1, T21D12.3. METHODOLOGY AND PRINCIPAL FINDINGS: We generated Venus
      transgenic and T21D12.3-mutant nematodes to analyze developmental expression
      patterns and in vivo functions of the nematode PQBP1 homologue protein (pqbp
      1.1). During development, pqbp-1.1 is expressed from cell proliferation stage to
      larva stage. In larva, intestinal cells show the highest expression of pqbp-1.1,
      while it decreases in adult worms. The mutants of pqbp-1.1 show a decrease of the
      lipid content in intestinal cells. Especially, incorporation of fatty acid into
      triglyceride is impaired. ShRNA-mediated repression of PQBP1 also leads to
      reduction of lipid content in mammalian primary white adipocytes. CONCLUSION/
      SIGNIFICANCE: These results suggest that pqbp-1.1 is involved in lipid metabolism
      of intestinal cells. Dysfunction of lipid metabolism might underlie lean body,
      one of the most frequent symptoms associating with PQBP1-linked MR patients.

PMID- 19119318
TI  - Display of cell surface sites for fibronectin assembly is modulated by cell
      adherence to (1)F3 and C-terminal modules of fibronectin.
AB  - BACKGROUND: Fibronectin-null cells assemble soluble fibronectin shortly after
      adherence to a substrate coated with intact fibronectin but not when adherent to
      the cell-binding domain of fibronectin (modules (7)F3-(10)F3). Interactions of
      adherent cells with regions of adsorbed fibronectin other than modules (7)F3
      (10)F3, therefore, are required for early display of the cell surface sites that
      initiate and direct fibronectin assembly. METHODOLOGY/PRINCIPAL FINDINGS: To
      identify these regions, coatings of proteolytically derived or recombinant pieces
      of fibronectin containing modules in addition to (7)F3-(10)F3 were tested for
      effects on fibronectin assembly by adherent fibronectin-null fibroblasts. Pieces
      as large as one comprising modules (2)F3-(14)F3, which include the heparin
      binding and cell adhesion domains, were not effective in supporting fibronectin
      assembly. Addition of module (1)F3 or the C-terminal modules to modules (2)F3
      (14)F3 resulted in some activity, and addition of both (1)F3 and the C-terminal
      modules resulted in a construct, (1)F3-C, that best mimicked the activity of a
      coating of intact fibronectin. Constructs (1)F3-C V0, (1)F3-C V64, and (1)F3-C
      Delta(V(15)F3(10)F1) were all able to support fibronectin assembly, suggesting
      that (1)F3 through (11)F1 and/or (12)F1 were important for activity. Coatings in
      which the active parts of (1)F3-C were present in different proteins were much
      less active than intact (1)F3-C. CONCLUSIONS: These results suggest that (1)F3
      acts together with C-terminal modules to induce display of fibronectin assembly
      sites on adherent cells.

PMID- 19119320
TI  - NOTCH2 is neither rearranged nor mutated in t(1;19) positive oligodendrogliomas.
AB  - The combined deletion of 1p and 19q chromosomal arms is frequent in
      oligodendrogliomas (OD) and has recently been shown to be mediated by an
      unbalanced t(1;19) translocation. Recent studies of 1p/19q co-deleted OD suggest
      that the NOTCH2 gene is implicated in oligodendrocyte differentiation and may be
      involved in this rearrangement. The objective of the present study was to analyze
      the NOTCH2 locus either as a chromosomal translocation locus that may be altered
      by the 1p/19q recurrent rearrangement or as a gene that may be inactivated by a
      two hit process. We performed an array-CGH analysis of 15 ODs presenting 1p/19q
      co-deletion using a high-density oligonucleotide microarray spanning 1p and 19q
      pericentromeric regions with 377 bp average probe spacing. We showed that the 1p
      deletion extends to the centromere of chromosome 1 and includes the entire NOTCH2
      gene. No internal rearrangement of this gene was observed. This strongly suggests
      that the t(1;19) translocation does not lead to an abnormal NOTCH2 structure. The
      analysis of the entire NOTCH2 coding sequence was performed in four cases and did
      not reveal any mutation therefore indicating that NOTCH2 does not harbor genetic
      characteristics of a tumor suppressor gene. Finally, the detailed analysis of
      chromosome 19 pericentromeric region led to the identification of two breakpoint
      clusters at 19p12 and 19q11-12. Interestingly, these two regions share a large
      stretch of homology. Together with previous observations of similarities between
      chromosome 1 and 19 alphoid sequences, this suggests that the t(1;19)
      translocation arises from complex intra and interchromosomal rearrangements.This
      is the first comprehensive deletion mapping by high density oligo-array of the
      1p/19q co-deletion in oligodendroglioma tumors using a methodological approach
      superior to others previously applied. As such this paper provides clear evidence
      that the NOTCH2 gene is not physically rearranged by t(1;19) translocation of
      oligodendroglioma tumors.

PMID- 19119321
TI  - Nevirapine resistance and breast-milk HIV transmission: effects of single and
      extended-dose nevirapine prophylaxis in subtype C HIV-infected infants.
AB  - BACKGROUND: Daily nevirapine (NVP) prophylaxis to HIV-exposed infants
      significantly reduces breast-milk HIV transmission. We assessed NVP-resistance in
      Indian infants enrolled in the "six-week extended-dose nevirapine" (SWEN) trial
      who received single-dose NVP (SD-NVP) or SWEN for prevention of breast-milk HIV
      transmission but who also acquired subtype C HIV infection during the first year
      of life. METHODS/FINDINGS: Standard population sequencing and cloning for viral
      subpopulations present at > or =5% frequency were used to determine HIV genotypes
      from 94% of the 79 infected Indian infants studied. Timing of infection was
      defined based on when an infant's blood sample first tested positive for HIV DNA.
      SWEN-exposed infants diagnosed with HIV by six weeks of age had a significantly
      higher prevalence of NVP-resistance than those who received SD-NVP, by both
      standard population sequencing (92% of 12 vs. 38% of 29; p = 0.002) and low
      frequency clonal analysis (92% of 12 vs. 59% of 29; p = 0.06). Likelihood of
      infection with NVP-resistant HIV through breast-milk among infants infected after
      age six weeks was substantial, but prevalence of NVP-resistance did not differ
      among SWEN or SD-NVP exposed infants by standard population sequencing (15% of 13
      vs. 15% of 20; p = 1.00) and clonal analysis (31% of 13 vs. 40% of 20; p = 0.72).
      Types of NVP-resistance mutations and patterns of persistence at one year of age
      were similar between the two groups. NVP-resistance mutations did differ by
      timing of HIV infection; the Y181C variant was predominant among infants
      diagnosed in the first six weeks of life, compared to Y188C/H during late breast
      milk transmission. CONCLUSIONS/SIGNIFICANCE: Use of SWEN to prevent breast-milk
      HIV transmission carries a high likelihood of resistance if infection occurs in
      the first six weeks of life. Moreover, there was a continued risk of transmission
      of NVP-resistant HIV through breastfeeding during the first year of life, but did
      not differ between SD-NVP and SWEN groups. As with SD-NVP, the value of
      preventing HIV infection in a large number of infants should be considered
      alongside the high risk of resistance associated with extended NVP prophylaxis.
      TRIAL REGISTRATION: ClinicalTrials.gov NCT00061321.

PMID- 19119322
TI  - Effect of a standardised dietary restriction protocol on multiple laboratory
      strains of Drosophila melanogaster.
AB  - BACKGROUND: Outcomes of lifespan studies in model organisms are particularly
      susceptible to variations in technical procedures. This is especially true of
      dietary restriction, which is implemented in many different ways among
      laboratories. PRINCIPAL FINDINGS: In this study, we have examined the effect of
      laboratory stock maintenance, genotype differences and microbial infection on the
      ability of dietary restriction (DR) to extend life in the fruit fly Drosophila
      melanogaster. None of these factors block the DR effect. CONCLUSIONS: These data
      lend support to the idea that nutrient restriction genuinely extends lifespan in
      flies, and that any mechanistic discoveries made with this model are of potential
      relevance to the determinants of lifespan in other organisms.

PMID- 19119323
TI  - An unusual helix turn helix motif in the catalytic core of HIV-1 integrase binds
      viral DNA and LEDGF.
AB  - BACKGROUND: Integrase (IN) of the type 1 human immunodeficiency virus (HIV-1)
      catalyzes the integration of viral DNA into host cellular DNA. We identified a bi
      helix motif (residues 149-186) in the crystal structure of the catalytic core
      (CC) of the IN-Phe185Lys variant that consists of the alpha(4) and alpha(5)
      helices connected by a 3 to 5-residue turn. The motif is embedded in a large
      array of interactions that stabilize the monomer and the dimer. PRINCIPAL
      FINDINGS: We describe the conformational and binding properties of the
      corresponding synthetic peptide. This displays features of the protein motif
      structure thanks to the mutual intramolecular interactions of the alpha(4) and
      alpha(5) helices that maintain the fold. The main properties are the binding to:
      1- the processing-attachment site at the LTR (long terminal repeat) ends of virus
      DNA with a K(d) (dissociation constant) in the sub-micromolar range; 2- the whole
      IN enzyme; and 3- the IN binding domain (IBD) but not the IBD-Asp366Asn variant
      of LEDGF (lens epidermal derived growth factor) lacking the essential Asp366
      residue. In our motif, in contrast to the conventional HTH (helix-turn-helix), it
      is the N terminal helix (alpha(4)) which has the role of DNA recognition helix,
      while the C terminal helix (alpha(5)) would rather contribute to the motif
      stabilization by interactions with the alpha(4) helix. CONCLUSION: The motif,
      termed HTHi (i, for inverted) emerges as a central piece of the IN structure and
      function. It could therefore represent an attractive target in the search for
      inhibitors working at the DNA-IN, IN-IN and IN-LEDGF interfaces.

PMID- 19119325
TI  - Multiscale Monte Carlo Sampling of Protein Sidechains: Application to Binding
      Pocket Flexibility.
AB  - We present a Monte Carlo sidechain sampling procedure and apply it to assessing
      the flexibility of protein binding pockets. We implemented a multiple "time step"
      Monte Carlo algorithm to optimize sidechain sampling with a surface generalized
      Born implicit solvent model. In this approach, certain forces (those due to long
      range electrostatics and the implicit solvent model) are updated infrequently, in
      "outer steps", while short-range forces (covalent, local nonbonded interactions)
      are updated at every "inner step". Two multistep protocols were studied. The
      first protocol rigorously obeys detailed balance, and the second protocol
      introduces an approximation to the solvation term that increases the acceptance
      ratio. The first protocol gives a 10-fold improvement over a protocol that does
      not use multiple time steps, while the second protocol generates comparable
      ensembles and gives a 15-fold improvement. A range of 50-200 inner steps per
      outer step was found to give optimal performance for both protocols. The
      resultant method is a practical means to assess sidechain flexibility in ligand
      binding pockets, as we illustrate with proof-of-principle calculations on six
      proteins: DB3 antibody, thermolysin, estrogen receptor, PPAR-gamma, PI3 kinase,
      and CDK2. The resulting sidechain ensembles of the apo binding sites correlate
      well with known induced fit conformational changes and provide insights into
      binding pocket flexibility.

PMID- 19119327
TI  - Just a woman.
AB  - A Lamaze childbirth educator explores her own transformative experience giving
      birth to her second child.

PMID- 19119326
TI  - Protective effects of (-)-epigallocatechin gallate on UVA-induced damage in
      ARPE19 cells.
AB  - PURPOSE: Oxidative injury to the retinal pigment epithelium (RPE) has been
      proposed to play a contributing role in age-related macular degeneration (AMD).
      Exposure to solar ultraviolet (UV) radiation is believed to cause the production
      of reactive oxygen species (ROS), which may cause oxidative damage to RPE cells.
      Studies have shown that (-)-epigallocatechin gallate (EGCG), an abundant and
      active component in green tea, can protect several cell types from oxidative
      stress. It may be useful in the prevention of early AMD. METHODS: To determine
      whether EGCG protects RPE cells from UVA-induced damage, we used a cell viability
      assay to determine the viability of UVA-treated cells. Intracellular H(2)O(2)
      levels were measured by flow cytometry. Western blotting was used to detect UVA
      induced signaling pathways. RESULTS: The results indicated that EGCG inhibits UVA
      induced RPE cell death. In addition, intracellular H(2)O(2) generation in RPE
      cells irradiated by UVA was inhibited by EGCG in a concentration-dependent
      manner. EGCG also inhibited UVA-induced extracullar signal-regulated kinase (ERK)
      and c-jun-NH2 terminal kinase (JNK) activation in RPE cells while a higher
      concentration of EGCG had an inhibitory effect on UVA-induced p38 activation.
      Finally, we investigated cyclooxygenase-2 (COX-2) expression in RPE cells exposed
      to UVA radiation, and EGCG was found to also have inhibited UVA-induced COX-2
      expression. CONCLUSIONS: Taken together, our results demonstrate that EGCG
      inhibits UVA-induced H(2)O(2) production, mitogen-activating protein kinase
      activation, and expression of COX-2. Moreover, it enhances RPE cell survival
      after UVA exposure. This suggests EGCG is effective in preventing UVA-induced
      damage in RPE cells and may be suitable for further developments as a
      chemoprotective factor for the primary prevention of early AMD.

PMID- 19119328
TI  - Hope in hard times.
AB  - In the face of challenging times, advocates for women and their families in
      maternal-child health care continue to promote evidence-based and mother-/baby
      friendly care. What qualities allow childbirth educators, doulas, nurses, and
      perinatal care providers to keep going even when the health-care practices around
      them often do not match their values? This editorial explores the impact of
      recent trends in which increasing utilization of elective technology in maternity
      care may affect the individual commitment of childbirth advocates. Borrowing from
      research on successful advocates in other fields, the author speculates on both
      why and how childbirth advocates sustain commitment and how "we will prevail."

PMID- 19119329
TI  - Contemporary Women's Perceptions of Childbirth Education.
AB  - The purpose of this grounded theory study was to describe and understand
      contemporary childbearing women's perceptions of the role of childbirth education
      in preparing for birth. Participants were interviewed three times: prior to
      beginning classes, at the end of classes, and within 2 weeks after giving birth.
      Constant comparative analysis of the data was concurrent with data collection.
      The core process that emerged was "Negotiating the Journey," with supporting
      categories of "Exploring the Unknown," "Making It Real," and "Sensing the
      Readiness." The findings indicated that, for contemporary women, the value of
      childbirth education may not be in affecting physiological birth outcomes but
      rather in helping them to be ready for childbirth and, thereby, completing an
      important developmental milestone.

PMID- 19119330
TI  - Visualizing motherhood: a photo intervention.
AB  - This article describes a simple, yet powerful postpartum intervention. The
      clinician gives each mother an instant photo taken of her with her newborn in the
      hospital a few hours or days after birth. For mothers, the photo becomes a
      snapshot-in-time to mark this memorable event. For clinicians, it represents a
      way to enhance an understanding of the mother with her newborn and facilitate the
      emotional connections between them.

PMID- 19119331
TI  - Promoting Healthy Pregnancies Through Perinatal Groups: A Comparison of
      CenteringPregnancy(R) Group Prenatal Care and Childbirth Education Classes.
AB  - CenteringPregnancy(R) group prenatal care is growing in popularity and has
      commonalities with childbirth education classes. In order for leaders of
      childbirth education classes to best serve their clients' needs, it is important
      to be aware of new, emerging models of prenatal care such as CenteringPregnancy.
      This article provides an overview of CenteringPregnancy and similarities and
      differences between CenteringPregnancy and childbirth education classes.
      Providers of prenatal education, whether it is within CenteringPregnancy group
      prenatal care or in childbirth education classes, have a common important aim:
      promoting positive perinatal outcomes.

PMID- 19119332
TI  - Choice, autonomy, and childbirth education.
AB  - In this column, a reader challenges the idea that choice in childbirth is a myth.
      The ways in which women's choices in childbirth are undermined are explored. The
      relationship between choice, autonomy, and decision-making is discussed. Autonomy
      is considered as a foundation for decision-making and an important way to make
      birth safer for mothers and babies. Strategies for increasing autonomy within the
      framework of childbirth education are presented.

PMID- 19119333
TI  - Normalizing the changes experienced during each trimester of pregnancy.
AB  - In this column, the various physical changes that may occur during each trimester
      of pregnancy are introduced in an activity that involves participants in
      childbirth education classes or in a waiting room of a prenatal care clinic. This
      lesson is intended to educate and reassure women of the normalcy of the changes
      they may experience throughout a pregnancy.

PMID- 19119334
TI  - Childhood overweight: prevention strategies for parents.
AB  - In recent years, childhood obesity has become a worldwide issue. The growing list
      of negative outcomes associated with its occurrence is constantly increasing the
      need for prevention and intervention. Although there is still much to learn about
      the causes and outcomes associated with childhood obesity, current empirical
      information is already available and should be used to influence good parenting
      practices. Observing good nutrition during pregnancy and prenatal monitoring;
      breastfeeding for 7 months and longer, if possible; introducing young children to
      healthy food in a positive context; and choosing physical activities are all
      important strategies for parents in preventing childhood obesity.

PMID- 19119335
TI  - Research summaries for normal birth.
AB  - In this column, the author summarizes four research studies relevant to normal
      birth. The studies summarized include a systematic review of trials evaluating
      the benefits versus harms of routine artificial rupture of the membranes; a study
      of the effect of continuous female labor support by a minimally trained family
      member or friend on attachment and early parenting; a systematic review examining
      the relationship between cesarean surgery and postpartum urinary incontinence;
      and a randomized controlled trial of warm perineal compresses during the second
      stage of labor.

PMID- 19119336
TI  - The eyes have it.
AB  - In this column, a childbirth educator considers the basis of her clients' fears
      and encourages readers to consider the roots of their own.

PMID- 19119337
TI  - Nonvestibular schwannoma tumors in the cerebellopontine angle: a structured
      approach and management guidelines.
AB  - The most common cerebellopontine angle (CPA) tumor is a vestibular schwannoma,
      but one in five CPA tumors are not vestibular schwannomas. These tumors may
      require different management strategies. Compared with vestibular schwannomas,
      symptoms and signs from cranial nerve VIII are less frequent: other cranial nerve
      and cerebellar symptoms and signs predominate in patients with these less common
      CPA tumors. Computed tomography and magnetic resonance imaging often show
      features leading to the correct diagnosis. Treatment most often includes surgery,
      but a policy of observation or subtotal resection is often wiser. This review
      provides a structured approach to the diagnosis of nonvestibular schwannoma CPA
      lesions and also management guidelines.

PMID- 19119339
TI  - Recurrence and outcome in skull base meningiomas: do they differ from other
      intracranial meningiomas?
AB  - BACKGROUND AND OBJECTIVES: Meningiomas have diverse presentations and the skull
      base harbors the most difficult of them to operate upon. The objective of this
      study was to learn whether the recurrence and outcome of these tumors may differ
      based on their location. DESIGN: Consecutive admissions with intracranial
      meningiomas between 1999 and 2004 were considered according to their location,
      WHO grade, recurrence, and outcome following treatment. RESULTS: There were 83
      skull base meningiomas and 86 at other locations. In 22 cases of skull base
      tumors there was recurrence (26.5%), while 15% (13) of the other group showed
      recurrence. There was no statistically significant difference in the outcome
      between the two groups; though skull base lesions had a better outcome based upon
      a raw count. Only 5.1% of skull base meningiomas in comparison to 10.6% of non
      skull base meningiomas had death or significant morbidity. Increasing age was
      associated with poor outcome (p < 0.001) while recurrence was a function of skull
      base location (p < 0.03) on logistic regression analysis. CONCLUSION: Skull base
      meningiomas can be operated upon with good outcome, which is comparable to the
      convexity meningiomas. Except for the increasing age, skull base location does
      not contribute to increased mortality or morbidity.

PMID- 19119338
TI  - Low complication rates of cranial and craniofacial approaches to midline anterior
      skull base lesions.
AB  - OBJECTIVE: Surgery is a cornerstone of treatment for a wide variety of
      neoplastic, congenital, traumatic, and inflammatory lesions involving the midline
      anterior skull base and may result in a significant anterior skull base defect
      requiring reconstruction. This study is a retrospective analysis of the
      reconstruction techniques and complications seen in a series of 58 consecutive
      patients with midline anterior skull base pathology treated with craniotomy or a
      craniofacial approach. The complication rates in this series are compared with
      other retrospective series and specific techniques that may reduce complications
      are then discussed. DESIGN: This is a retrospective analysis of 58 consecutive
      patients who had surgery for a midline anterior skull base lesion between January
      1994 and July 2003. Data were collected regarding pathology, surgical approach,
      reconstruction technique, and complications. RESULTS: Twenty-nine patients
      underwent surgery for a meningioma (50%). The remainder had frontoethmoidal
      cancer, mucoceles/invasive nasal polyps, encephalocele, esthesioneuroblastoma,
      anterior falx dermoid cyst with a nasal sinus tract, or invasive pituitary
      adenoma. In most patients, a low and narrow two-piece biorbitofrontal craniotomy
      was used. When possible, the dura was repaired before entering the nasal cavity.
      Thirteen patients experienced a complication (22%). There was one case of
      postoperative cerebrospinal fluid (CSF) leak (2%), one case of meningitis (2%),
      two cases of bone flap infection (3%), and two cases of symptomatic
      pneumocephalus (3%). There were no deaths, no reoperations for CSF leak, and no
      patient had a new permanent neurologic deficit other than anosmia. CONCLUSIONS:
      Transcranial approaches for midline anterior skull base lesions can be performed
      safely with a low incidence of postoperative CSF leak, meningitis, bone flap
      infection, and symptomatic pneumocephalus. Our results, particularly with regard
      to CSF leakage, compare favorably with other retrospective series.

PMID- 19119340
TI  - Temporalis myofascial flap for primary cranial base reconstruction after tumor
      resection.
AB  - OBJECTIVE: To evaluate the use of the temporalis myofascial flap in primary
      cranial base reconstruction following surgical tumor ablation and to explain
      technical issues, potential complications, and donor site consequences along with
      their management. DESIGN: Retrospective case series. SETTING: Tertiary referral
      center. PARTICIPANTS: Forty-one consecutive patients receiving primary temporalis
      myofascial flap reconstructions following cranial base tumor resections in a 4
      year period. MAIN OUTCOME MEASURES: Flap survival, postoperative complications,
      and donor site morbidity. RESULTS: Patients included 37 males and 4 females
      ranging in age from 10 to 65 years. Two patients received preoperative and 18
      postoperative radiation therapy. Patient follow-up ranged from 4 to 39 months.
      The whole temporalis muscle was used in 26 patients (63.4%) and only part of a
      coronally split muscle was used in 15 patients (36.6%). Nine patients had primary
      donor site reconstruction using a Medpor((R)) (Porex Surgical, Inc., Newnan, GA)
      temporal fossa implant; these had excellent aesthetic results. There were no
      cases of complete flap loss. Partial flap dehiscence was seen in six patients
      (14.6%); only two required surgical debridement. None of the patients developed
      cerebrospinal leaks or meningitis. One patient was left with complete paralysis
      of the temporal branch of the facial nerve. Three patients (all had received
      postoperative irradiation) developed permanent trismus. CONCLUSIONS: The
      temporalis myofascial flap was found to be an excellent reconstructive
      alternative for a wide variety of skull base defects following tumor ablation. It
      is a very reliable, versatile flap that is usually available in the operative
      field with relatively low donor site aesthetic and functional morbidity.

PMID- 19119341
TI  - Anterior Communicating Artery Aneurysm Surgery through the Orbitopterional
      Approach: Long-Term Follow-Up in a Series of 75 Consecutive Patients.
AB  - OBJECTIVE: In this retrospective review of prospectively collected data, we
      report outcomes for patients with anterior communicating artery (ACoA) aneurysms
      treated via the orbitopterional approach and discuss the potential impact in
      patient outcomes by the reduction of surgery-induced brain damage. METHODS: We
      retrospectively reviewed prospectively collected data from 40 men and 35 women
      (mean age, 50.8 years) who underwent clipping of ACoA aneurysms through the
      orbitopterional approach. RESULTS: Overall outcomes at discharge using the
      modified Rankin Scale were good in 52 (69.4%) patients, fair in 13 (17.3%), and
      poor in 10 (13.3%). At last follow-up, outcomes were good in 63 (84%) patients,
      fair in 6 (8%), and poor in 6 (8%). Disability included none in 53.6% patients,
      mild in 10%, partial in 18.8%, moderate in 8.6%, moderately severe in 1.4%,
      severe in 2.9%, extremely severe in 2.9%, and vegetative state in 1.4%. Overall,
      74% of patients returned to work after 4 months, 83% of previously unemployed
      patients returned to baseline, and 25% were disabled. Complications were more
      frequent and severe after subarachnoid hemorrhage. CONCLUSIONS: Long-term follow
      up data present the orbitopterional approach as an attractive alternative for
      ACoA aneurysm surgery given the low rates of surgery-related morbidity and good
      patient outcomes and functionality.

PMID- 19119342
TI  - Single-stage complex reconstruction for fibrous dysplasia: a case report.
AB  - OBJECTIVE AND IMPORTANCE: Fibrous dysplasia is a benign skeletal condition which
      can involve the craniofacial skeleton. Surgery is indicated for correction of
      deformity and neurovascular decompression. Traditional surgery involves
      harvesting remote bone or calvarial grafts, requiring prolonged, multisite
      procedures. Custom implants may eliminate the need for bone harvesting, but
      usually require staged procedures with interim bony defects. We report the use of
      preoperative cranial modeling and implant design, allowing for a single
      reconstructive procedure. CLINICAL PRESENTATION: A 32-year-old woman with McCune
      Albright syndrome was referred to Neurosurgery and Ophthalmology for right facial
      pain, deformity, and eye pressure. Examination revealed a 6-mm right eye
      proptosis and decreased sensation and severe pain in the right V2 distribution.
      Imaging demonstrated extensive fibrous dysplasia, with right orbital mass effect
      and nerve compression. INTERVENTION: A single procedure was planned to remove and
      replace the involved bone. High-resolution CT was used to create a scale model of
      the patient's cranium. The planned resection was performed on the model, allowing
      for preoperative custom implant design. We then performed single-stage resection
      and reconstruction. The right superior and lateral orbital rims, portions of the
      left superior and medial orbital rims, and the nasion were resected. The custom
      implant was contoured to fit and remaining small defects were filled with Fast
      Set Norian. No complications occurred. At follow-up, the patient reported pain
      and pressure relief, and examination showed resolution of proptosis, improved
      sensation, and excellent cosmesis. CONCLUSION: Preoperative cranial modeling and
      implant design allows for a shorter, one-step resection and reconstruction
      procedure without compromising structural or cosmetic outcome.

PMID- 19119344
TI  - Changes.

PMID- 19119343
TI  - CNAP To Predict Functional Cochlear Nerve Preservation in NF-2: Cochlear Implant
      or Auditory Brainstem Implant.
AB  - The ideal management of bilateral vestibular schwannomas (VSs) involves complete
      tumor resection with preservation of hearing in at least one ear. While auditory
      brainstem implants (ABIs) have represented a significant advance in the
      management of neurofibromatosis type 2 (NF-2) patients, hearing rehabilitation is
      far from ideal. More recently, cochlear implantation has been used in selected
      cases of NF-2, following tumor removal, where the patient is left with bilateral
      profound hearing loss but with anatomical continuity of the cochlear nerve. In
      selected cases, cochlear implant (CI) has given superior results to ABI. The
      Gruppo Otologico experience in managing NF-2 patients consists of 29 patients
      treated between December 1996 and December 2007 out of a total of 1723 VSs.
      Thirty-nine tumors have been removed, with 10 patients having had bilateral tumor
      removed. Ten ABIs have been implanted and 5 CIs placed. We present a case that
      illustrates some of the difficulties encountered in the management of NF-2 VS and
      provides a basis for discussion of a technique to assist intraoperative decision
      making to achieve optimal hearing rehabilitation. In the setting of a negative
      fast auditory brainstem response (ABR), but preserved cochlear nerve action
      potential (CNAP), the option of a CI can be considered. However, where the fast
      ABR and the morphology and amplitude of the CNAP are significantly degraded at
      the brainstem, the placement of an ABI should be strongly considered at the time
      of tumor removal. This technique must be further evaluated, but it represents an
      adjunct in this difficult area for the neurotologist. To this end we propose that
      a multicenter trial be undertaken to further elucidate the role of intraoperative
      monitoring to determine the functional preservation of the cochlear nerve.

PMID- 19119345
TI  - Adolescent medicine in Canada: A positive step for paediatricians and
      adolescents.

PMID- 19119346
TI  - Adolescent medicine: A new paediatric subspecialty in Canada.

PMID- 19119347
TI  - What teenagers want: Tips on working with today's youth.

PMID- 19119348
TI  - Adherence to treatment in adolescents.
AB  - Health care professionals must be alert to the high prevalence of low adherence
      to treatment during adolescence. Low adherence increases morbidity and medical
      complications, contributes to poorer quality of life and an overuse of the health
      care system. Many different factors have an impact on adherence. However,
      critical factors to consider in teens are their developmental stage and
      challenges, emotional issues and family dysfunction. Direct and indirect methods
      have been described to assess adherence. Eliciting an adherence history is the
      most useful way for clinicians to evaluate adherence, and could be the beginning
      of a constructive dialogue with the adolescent. Interventions to improve
      adherence are multiple - managing mental health issues appropriately, building a
      strong relationship, customizing the treatment regimen if possible, empowering
      the adolescent to deal with adherence issues, providing information, ensuring
      family and peer support, and motivational enhancement therapy. Evaluation of
      adherence at regular intervals should be an important aspect of health care for
      adolescents.

PMID- 19119349
TI  - Sex and sexual health: A survey of Canadian youth and mothers.
AB  - INTRODUCTION: Apparent changes in adolescent sexual behaviours have led to debate
      in recent years. A survey on adolescent sexuality was designed to determine
      mainstream Canadian adolescents' current knowledge and sources of sexual health
      information, to identify their needs, and to understand the perceptions and the
      role of parents in sexual health education. METHODOLOGY: In October 2005, on-line
      interviews were conducted by Ipsos Reid (Ipsos Canada) with 1171 Canadian
      teenagers (14 to 17 years of age) and 1139 mothers of teenagers. RESULTS: Twenty
      seven per cent of teens were sexually active at a mean age of 15 years, with an
      average of 2.5 lifetime partners, and had been in their current relationship for
      longer than eight months. The last time that they had had sex, 76% had used a
      condom. Teens and mothers overestimated the percentages of teens sexually active
      at any age. Most valuable sources of information were school, parents, friends
      and doctors. Sixty-nine per cent of teens could not find the information that
      they were looking for, and 62% reported obstacles in getting information. Teens
      lacked knowledge about sexually transmitted infections and their consequences.
      Seventy-five per cent of mothers believed that their teenagers' friends were
      significant role models when it came to sexuality, and 50% mentioned
      entertainment celebrities at par with them. However, 45% of teenagers regarded
      their parents as their role models, far ahead of friends (32%) and entertainment
      celebrities (15%). Despite saying that they had positive relationships with their
      mothers, 38% of teens had not discussed sexuality with them. Most teens trusted
      the information given by health professionals (94%) and believed that it was
      their role to provide sexual health information. CONCLUSIONS: Most adolescents
      are responsible when it comes to sexuality, but there are still areas of concern.
      Adolescents identify barriers to getting information and lack knowledge about
      sexually transmitted infections. Parents should feel more comfortable when it
      comes to discussing sexuality, especially the more value-based issues. Health
      care professionals and teachers have a role to play, and should ensure that teens
      are getting correct information. It is important to have diverse sources of
      information. All teens are not ready at the same time to receive the information;
      thus, it should be repeated. Governments, health, education and public health
      authorities have an essential role to play to make sexual health information
      accurate, accessible, inclusive and salient to the reality of Canadian
      adolescents.

PMID- 19119350
TI  - Adolescent male health.
AB  - Although adolescent males have as many health issues and concerns as adolescent
      females, they are much less likely to be seen in a clinical setting. This is
      related to both individual factors and the health care system itself, which is
      not always encouraging and set up to provide comprehensive male health care.
      Working with adolescent boys involves gaining the knowledge and skills to address
      concerns such as puberty and sexuality, substance use, violence, risk-taking
      behaviours and mental health issues. The ability to engage the young male patient
      is critical, and the professional must be comfortable in initiating conversation
      about a wide array of topics with the teen boy, who may be reluctant to discuss
      his concerns. It is important to take every opportunity with adolescent boys to
      talk about issues beyond the presenting complain, and let them know about
      confidential care. The physician can educate teens about the importance of
      regular checkups, and that they are welcome to contact the physician if they are
      experiencing any concerns about their health or well-being. Parents of
      preadolescent and adolescent boys should be educated on the value of regular
      health maintenance visits for their sons beginning in their early teen years.

PMID- 19119351
TI  - The tired teen: A review of the assessment and management of the adolescent with
      sleepiness and fatigue.
AB  - The symptoms of sleepiness and fatigue are frequently encountered when caring for
      adolescents. Up to 40% of healthy teens experience regular sleepiness, defined as
      an increased tendency to fall asleep. Fatigue is the perception of low energy
      following normal activity and is reported by up to 30% of well teens. Chronic
      fatigue syndrome is an unusual syndrome with severe fatigue accompanied by other
      physical and neurological symptoms. A thorough assessment is required for all
      teens with sleepiness and fatigue; however, a treatable underlying medical
      condition is rarely found. Most fatigue and sleepiness in teens is attributable
      to lifestyle issues, notably too little time spent sleeping. Physicians are in a
      position to screen for, assess and manage these common conditions in teens.

PMID- 19119352
TI  - Surveying adolescents: Focusing on positive development.
AB  - Although risk behaviours can threaten healthy youth development, reducing risks
      alone is not sufficient to help youth successfully negotiate adolescence.
      Promoting protective factors that buffer risk, such as family and school
      connectedness, community engagement and positive peer support, are also important
      for helping youth to thrive. Since 1992, the Adolescent Health Surveys conducted
      by McCreary Centre Society (Vancouver, British Columbia) have monitored both risk
      behaviours and protective factors among high school students across British
      Columbia. They have shown that, contrary to media images and community
      perceptions, the majority of young people are not exposed to risk factors such as
      violence and abuse; most do not have unprotected sex, drink and drive, use
      illegal drugs or consider suicide. They have also documented key protective
      factors that are linked to lower rates of risk behaviours and more positive
      outcomes, even for youth who face unsafe environments, family problems and other
      stressors. The shift toward assessing and promoting protective factors is a major
      paradigm change in adolescent health care, and clinicians can be an important
      partner with families and schools to foster healthy youth development.

PMID- 19119353
TI  - Case 1: The need for speed.

PMID- 19119354
TI  - Case 2: Rash, fever and headache....first, do no harm.

PMID- 19119355
TI  - Harm reduction: An approach to reducing risky health behaviours in adolescents.

PMID- 19119356
TI  - Issues of care for hospitalized youth.

PMID- 19119357
TI  - Teens and sleep: Why you need it and how to get enough.

PMID- 19119358
TI  - Rickets: A re-emerging public health problem in Canada?

PMID- 19119359
TI  - Who is responsible for the efficacy and safety of pet foods?

PMID- 19119360
TI  - Who is responsible for the efficacy and safety of pet foods?

PMID- 19119361
TI  - Who is responsible for the efficacy and safety of pet foods?

PMID- 19119364
TI  - Information - filtered and unfiltered.

PMID- 19119365
TI  - An ethicist's commentary on whether students should determine curriculum.

PMID- 19119366
TI  - Antimicrobial resistance and prevalence of canine uropathogens at the Western
      College of Veterinary Medicine Veterinary Teaching Hospital, 2002-2007.
AB  - Between January 2002 and June 2007, uropathogens were isolated from 473 of 1557
      canine urine samples submitted to Prairie Diagnostic Services from the Western
      College of Veterinary Medicine Veterinary Teaching Hospital. Culture and
      susceptibility results were analyzed, retrospectively, to estimate the prevalence
      of common bacterial uropathogens in dogs with urinary tract infections and to
      identify changes in antimicrobial resistance. The most common pathogens
      identified were Escherichia coli, Staphylococcus intermedius, Enterococcus spp.,
      and Proteus spp. Antimicrobial resistance increased during the study period,
      particularly among recurrent E. coli isolates. Using the formula to help select
      rational antimicrobial therapy (FRAT), bacterial isolates were most likely to be
      susceptible to gentamicin, fluoroquinolones, amoxicillin-clavulanic acid, and
      groups 4 and 5 (third generation) cephalosporins.

PMID- 19119367
TI  - Vaginal lactic acid bacteria in healthy and ill bitches and evaluation of in
      vitro probiotic activity of selected isolates.
AB  - The concentrations of lactic acid bacteria (LAB) in 42 vaginal samples from
      healthy and ill bitches were determined. Eight isolates belonging to the genera
      Lactobacillus and Enterococcus were selected and identified and their in vitro
      antimicrobial activity against canine pathogens and their ability to adhere to
      canine vaginal epithelial cells were determined. There was no correlation between
      the concentrations of vaginal LAB and clinical status, body temperature, vaginal
      pH, or age. Although the animals were either well or suffering from various
      illnesses, LAB were found in almost every sample, and the selected isolates
      showed promising probiotic-related features. These findings are significant for
      the design of strategies for the modulation of vaginal microbiota by vaginal LAB
      isolates.

PMID- 19119368
TI  - Demographics and career path choices of graduates from three Canadian veterinary
      colleges.
AB  - The classes of 2007 from the Atlantic Veterinary College, Ontario Veterinary
      College, and Western College of Veterinary Medicine were surveyed to determine
      what factors influenced the respondents' career path choices. Seventy percent
      (166/237) of those contacted participated in the survey of which 89.1% were
      female, 62.7% had an urban upbringing, and 33.0% expected to be employed in a
      small center (population < or = 10,000). Half (52.5%) of the respondents reported
      that they were interested in mixed or food animal practice at the time of entry
      into veterinary college, but this proportion declined to 34.2% by the time of
      graduation. Three factors were significantly associated with choosing a career in
      mixed or food animal practice: having been raised in a small center, being a
      male, and having a good to excellent knowledge of food animal production at the
      time of entry into veterinary college, as determined by a self-assessment.

PMID- 19119369
TI  - Spontaneous left medial liver lobe torsion and left lateral lobe infarction in a
      rottweiler.
AB  - The abdominal ultrasonogram of a dog admitted for acute onset of collapse
      revealed an abnormally displaced left medial liver lobe with no blood flow.
      Surgical and histological findings confirmed the ultrasonographic diagnosis of
      left liver lobe torsion. Ultrasonographic findings were useful and probably
      sufficient for a correct diagnosis.

PMID- 19119370
TI  - Disseminated Leishmania infantum infection in two sibling foxhounds due to
      possible vertical transmission.
AB  - Two sibling foxhounds born to a Leishmania seropositive bitch were presented
      after testing seropositive for Leishmania. Leishmania infantum infection was
      detected via histopathology, culture, and quantitative polymerase chain reaction
      (q-PCR). This is the first report of natural infection with Leishmania infantum
      with the possibility for vertical transmission in North America.

PMID- 19119372
TI  - Ethylene glycol toxicosis in adult beef cattle fed contaminated feeds.
AB  - Acute deaths of cows held in a drylot and fed several crop processing plant by
      products were investigated. Clinical signs in affected cows included diarrhea,
      ataxia, recumbency, hypersalivation, and sunken eyes. A histological diagnosis of
      ethylene glycol toxicosis, based on numerous birefringent crystals in renal
      tubules, was supported by toxicologic findings.

PMID- 19119373
TI  - What veterinary clients really want, too?

PMID- 19119374
TI  - Frequently asked questions in orthopedics.

PMID- 19119371
TI  - Concepts for the clinical use of stem cells in equine medicine.
AB  - Stem cells from various tissues hold great promise for their therapeutic use in
      horses, but so far efficacy or proof-of-principle has not been established. The
      basic characteristics and properties of various equine stem cells remain largely
      unknown, despite their increasingly widespread experimental and empirical
      commercial use. A better understanding of equine stem cell biology and concepts
      is needed in order to develop and evaluate rational clinical applications in the
      horse. Controlled, well-designed studies of the basic biologic characteristics
      and properties of these cells are needed to move this new equine research field
      forward. Stem cell research in the horse has exciting equine specific and
      comparative perspectives that will most likely benefit the health of horses and,
      potentially, humans.

PMID- 19119375
TI  - Unilateral phacoemulsification and intraocular lens implantation in a dachshund.
AB  - A 1.5-year-old, spayed, female dachshund was presented with a cataract and lens
      induced uveitis in the left eye. The cataract progressed from immature to
      hypermature in 4 months. Phacoemulsification and intraocular lens implantation
      was performed and the dog remains visual in the left eye 1 year post-surgery.

PMID- 19119376
TI  - Inclusion of Mechanical Diagnosis and Therapy (MDT) in the Management of Cervical
      Radiculopathy: A Case Report.
AB  - Various interventions are used by physical therapists to treat neck conditions.
      Treatments may include exercises based on a direction of preference, cervical
      spine stabilization, neuromobilization, or traction. The purpose of this case
      study was to describe the use of mechanical diagnosis and therapy (MDT) in the
      management of a patient diagnosed with cervical radiculopathy. The case study
      involved a 39-year-old male (subject), classified with cervical derangement,
      hypermobility, and adverse neural tension. The subject's intervention included
      MDT, deep neck flexor muscle strengthening, and neuromobilization. This subject's
      scores on the Neck Disability Index, Numerical Pain Rating Scale (NPRS), and
      range of motion were assessed at initial examination, discharge, and 3-month
      follow-up. The subject improved on all outcome measures and was discharged after
      four visits with a NPRS of 0/10. Percent improvement per visit was 17.5%. This
      case describes a positive outcome for a patient diagnosed with cervical
      radiculopathy in which MDT, deep neck flexor strengthening, and neuromobilization
      were used as an alternative to cervical traction.

PMID- 19119377
TI  - American Academy of Orthopedic Manual Physical Therapy (AAOMPT): History,
      Advocacy, and Education.

PMID- 19119379
TI  - Philosophical differences in manual therapy.

PMID- 19119378
TI  - Intrinsic and extrinsic factors important to manual therapy competency
      development: a delphi investigation.
AB  - A learner's development of orthopaedic manual physical therapy (OMPT) psychomotor
      skills may be influenced by selected intrinsic and extrinsic factors. The
      purposes of this study were to identify the factors that influence learners'
      development of manual physical therapy competencies and to define each factor as
      intrinsic or extrinsic. A 3-round Delphi method survey and a retrospective review
      of the data were used to develop composite scores and rankings. Eighty manual
      physical therapy educators participated in the 3 rounds. Thirty-six factor
      descriptor statements associated with manual physical therapy competency were
      established and further categorized as intrinsic (19 total), extrinsic (10
      total), or conceptual outliers (7 total). Cognitive Processing ranked as the most
      important factor influencing manual physical therapy competency development.
      Adaptation ranked second, followed by Science Knowledge. This study is the first
      to establish manual physical therapy educational factors associated with
      attainment of competency. The majority of the factors distill into the theory of
      extrinsic and intrinsic factors identified by Schmidt and Lee. The outcomes of
      this study identify the factors to which OMPT educators should give particular
      attention when developing and executing the learning experiences for their
      learners.

PMID- 19119381
TI  - Neural mobilization: a systematic review of randomized controlled trials with an
      analysis of therapeutic efficacy.

PMID- 19119380
TI  - Neural mobilization: a systematic review of randomized controlled trials with an
      analysis of therapeutic efficacy.
AB  - Neural mobilization is a treatment modality used in relation to pathologies of
      the nervous system. It has been suggested that neural mobilization is an
      effective treatment modality, although support of this suggestion is primarily
      anecdotal. The purpose of this paper was to provide a systematic review of the
      literature pertaining to the therapeutic efficacy of neural mobilization. A
      search to identify randomized controlled trials investigating neural mobilization
      was conducted using the key words neural mobilisation/mobilization, nerve
      mobilisation/mobilization, neural manipulative physical therapy, physical
      therapy, neural/nerve glide, nerve glide exercises, nerve/neural treatment,
      nerve/neural stretching, neurodynamics, and nerve/neural physiotherapy. The
      titles and abstracts of the papers identified were reviewed to select papers
      specifically detailing neural mobilization as a treatment modality. The PEDro
      scale, a systematic tool used to critique RCTs and grade methodological quality,
      was used to assess these trials. Methodological assessment allowed an analysis of
      research investigating therapeutic efficacy of neural mobilization. Ten
      randomized clinical trials (discussed in 11 retrieved articles) were identified
      that discussed the therapeutic effect of neural mobilization. This review
      highlights the lack in quantity and quality of the available research.
      Qualitative analysis of these studies revealed that there is only limited
      evidence to support the use of neural mobilization. Future research needs to re
      examine the application of neural mobilization with use of more homogeneous study
      designs and pathologies; in addition, it should standardize the neural
      mobilization interventions used in the study.

PMID- 19119382
TI  - Three-dimensional movements of the sacroiliac joint: a systematic review of the
      literature and assessment of clinical utility.
AB  - The high frequency of static and dynamic palpation methods used during evaluation
      of SIJ problems in clinical practice demands an understanding of the factual
      quantity of movement at the SIJ. The objective of this systematic literature
      review was to synthesize three-dimensional (3-D) motion of the sacroiliac joint
      (SIJ) during various functional static postures and movements and to determine
      the clinical utility of movement during examination. A computer-based search was
      performed by means of OVID, which included Medline (February 1966 to April 2007)
      and CINAHL (February 1982 to April 2007) using the key words Pelvis, Kinematics,
      Imaging, Three-dimensional, and Stereophotogrammetric. Articles included in-vivo
      or in-vitro studies that investigated human SIJs with 3-D analysis. Three
      dimensional analyses conducted using mathematical modeling, computerized
      modeling, and/or skin markers were not included because of concerns of
      transferability and validity. Studies that failed to report standard error of
      measurement (SEM) or defined tabulated values for translations or rotations using
      the Cartesian coordinate system were not considered for this study. Studies
      included for review were analyzed by the SBC biomechanical checklist to measure
      the quality of procedural design. Seven manuscripts were eligible for inclusion
      in this study. Rotation ranged between -1.1 to 2.2 degrees along the X-axis, -0.8
      to 4.0 degrees along the Y-axis, and -0.5 to 8.0 degrees along the Z-axis.
      Translation ranged between -0.3 to 8.0 millimeters (mm) along the X-axis, -0.2 to
      7.0 mm along the Y-axis, -0.3 to 6.0 mm along the Z-axis. Motion of the SIJ is
      limited to minute amounts of rotation and of translation suggesting that clinical
      methods utilizing palpation for diagnosing SIJ pathology may have limited
      clinical utility.

PMID- 19119383
TI  - Manual therapy and cervical arterial dysfunction, directions for the future: a
      clinical perspective.
AB  - This paper offers a contemporary, evidence-based perspective on the issue of
      adverse neurovascular events related to cervical spine manual therapy. The
      purpose of this perspective is to challenge traditional thought and practice and
      to recognize areas where practice and research should develop. By considering the
      themes presented in this paper, the clinician can broaden his or her approach to
      neurovascular assessment in line with contemporary evidence and thought. We
      present information based on clinically relevant questions. The nature of
      vertebrobasilar insufficiency and the utility of pre-treatment testing are
      examined in light of contemporary evidence. In addition, we report on internal
      carotid artery pathology, and the significance of appreciating atherosclerosis in
      clinical decision-making. These later two areas are not commonly recognized
      within manual therapy literature, and we suggest that their importance to
      differential diagnosis of head and neck pain, as well as estimating treatment
      related risk, is paramount. We propose that the term cervical arterial
      dysfunction is more appropriate than classically used nomenclature. This term
      refers more accurately and completely to the range of pathologies at different
      anatomical sites that manual therapists treating patients with head and neck pain
      are likely to encounter. Finally, we present a brief review of the medico-legal
      status pertaining to this area. Although this is English law-related, the themes
      derived from this section are of interest to all manual therapists.

PMID- 19119384
TI  - Manual therapy and cervical arterial dysfunction, directions for the future: a
      clinical perspective.

PMID- 19119385
TI  - A model for standardizing manipulation terminology in physical therapy practice.

PMID- 19119386
TI  - Manual therapy awards and abstracts 2007.

PMID- 19119387
TI  - Concurrent criterion-related validity of physical examination tests for hip
      labral lesions: a systematic review.
AB  - Hip injuries are prevalent, especially within the athletic population. Of the hip
      injuries in this population, some 18-55% are lesions to the labrum of the hip.
      Clinical diagnosis of hip labral lesions is difficult because data on prevalence
      are varied. In addition, data on the prevalence of internal and external risk
      factors are absent as are data on the correlation of these risk factors with
      labral lesions, making it difficult to gauge the diagnostic utility. The
      mechanism of injury is often unknown or not specific to labral lesions. Internal
      risk factors may remain hidden to physical therapists because in most
      jurisdictions, ordering imaging tests is not within their scope of practice.
      Anterior inguinal pain seems highly sensitive for the diagnosis of patients with
      labral lesions but can hardly be considered specific; data on other pain-related
      and mechanical symptoms clearly have little diagnostic utility, making these data
      collected during the patient history almost irrelevant to diagnosis. By way of a
      comprehensive literature review and narrative and systematic analysis of the
      methodological quality of the retrieved diagnostic utility studies, this paper
      aimed to determine a diagnostic physical examination test or test cluster based
      on current best evidence for the diagnosis of hip labral lesions. Current best
      evidence indicates that a negative finding for the flexion-adduction-internal
      rotation test, the flexion-internal rotation test, the impingement provocation
      test, the flexion-adduction-axial compression test, the Fitzgerald test, or a
      combination of these tests provides the clinician with the greatest evidence
      based confidence that a hip labral lesion is absent. Currently, research has
      produced no tests with sufficient specificity to help confidently rule in a
      diagnosis of hip labral lesion. Suggestions for future research are provided.

PMID- 19119388
TI  - Chronic mechanical neck pain in adults treated by manual therapy: a systematic
      review of change scores in randomized controlled trials of a single session.
AB  - We report a systematic analysis of group change scores of subjects with chronic
      neck pain not due to whiplash and without headache or arm pain, in randomized
      clinical trials of a single session of manual therapy. A comprehensive literature
      search of clinical trials of chronic neck pain treated with manual therapies up
      to December 2006 was conducted. Trials that scored above 60% on the PEDro Scale
      were included. Change scores were analyzed for absolute, percentage change and
      effect size (ES) whenever possible. Nine trials were identified: 6 for spinal
      manipulation, 4 for spinal mobilization or non-manipulative manual therapy (2
      overlapping trials), and 1 trial using ischemic compression. No trials were
      identified for massage therapy or manual traction. Four manipulation trials (five
      groups) reported mean immediate changes in 100-mm VAS of -18.94 (9.28) mm. ES for
      these changes ranged from .33 to 2.3. Two mobilization trials reported immediate
      VAS changes of -11.5 and -4 mm (ES of .36 and .22, respectively); one trial
      reported no difference in immediate pain scores versus sham mobilization. The
      ischemic compression study showed statistically significant immediate decreases
      in 100-mm pain VAS (average = -14.6 mm). There is moderate-to-high quality
      evidence that immediate clinically important improvements are obtained from a
      single session of spinal manipulation. The evidence for mobilization is less
      substantial, with fewer studies reporting smaller immediate changes. There is
      insufficient evidence for ischemic compression to draw conclusions. There is no
      evidence for a single session of massage or manual traction for chronic neck
      pain.

PMID- 19119389
TI  - Potential pitfalls of clinical prediction rules.

PMID- 19119391
TI  - Clinical evaluation of cervicogenic headache: a clinical perspective.

PMID- 19119390
TI  - Clinical evaluation of cervicogenic headache: a clinical perspective.
AB  - Headache is a common complaint that affects the majority of the population at
      some point in their lives. The underlying pathological bases for headache
      symptoms are many, diverse, and often difficult to distinguish. Classification of
      headache is principally based on the evaluation of headache symptoms as well as
      clinical testing. Although manual therapy has been advocated to treat a variety
      of different forms of headache, the current evidence only supports treatment for
      cervicogenic headache (CGH). This form of headache can be identified from
      migraine and other headache forms by a comprehensive musculoskeletal examination.
      Examination and subsequent diagnosis is essential not only to identify patients
      with headache where manual therapy is appropriate but also to form a basis for
      selection of the most appropriate treatment for the identified condition. The
      purpose of this paper is to outline, in clinical terms, the classification of
      headache, so that the clinician can readily identify those patients with headache
      suited to manual therapy.

PMID- 19119392
TI  - Identifying myelopathy caused by thoracic syringomyelia: a case report.
AB  - Myelopathy is a form of neurological disease caused by compression of the spinal
      cord. Upper and lower quarter screens are commonly used in identifying
      myelopathy, although most of the screen components demonstrate poor or unstudied
      diagnostic value. The purpose of this case report is to describe the diagnostic
      process in detecting syringomyelia, an intramedullary lesion that may cause
      myelopathy. The patient was a 47-year-old female with a thoracic syrinx that was
      discovered by spinal magnetic resonance imaging (MRI) following a complicated and
      delayed clinical diagnostic course. Following surgical intervention and a two
      week inpatient rehabilitation stay, the patient was discharged using a rolling
      walker for ambulation and was performing most transfers with modified
      independence. A complicating pattern of signs and symptoms combined with a
      diagnostic process guided by poorly studied screen components demonstrates the
      diagnostic dilemma associated with identifying the cause of myelopathy within the
      thoracic spine. This also indicates the need for further investigation of
      individual and clustered components of the neurological screen to improve the
      ability to identify patients in need of complete imaging studies in a more timely
      fashion.

PMID- 19119393
TI  - Ultrasonographic measurement of neck muscle recruitment: a preliminary
      investigation.
AB  - Chronic cervical pain is a common source of disability in society, and evidence
      suggests that individuals with neck pain have impairment of the deep cervical
      flexor (DCF) muscles. This study investigated the recruitment pattern of the neck
      muscles, particularly the DCF, during the Craniocervical Flexion Test (CCFT),
      using ultrasound measurement of muscle activity in asymptomatic subjects. In a
      cross-sectional design, 10 subjects, of both sexes, with no history of neck pain
      participated in the study. Participants were instructed to perform the CCFT, and
      changes in thickness from resting baseline values during the five incremental
      stages of the test were obtained for DCF and sternocleidomastoid (SCM) muscles
      using ultrasonography. The most significant changes found in DCF thickness were
      between phase 1 and phases 4 (p<0.001) and 5 (p= <0.001). For SCM, differences
      were most significant between phases 1 and 3 (p<0.001), 4 (p<0.001), and 5
      (p<0.001); and between phases 3 and 5 (p<0.003). No differences were found
      between DCF and SCM muscles. The present study confirms the evidence that CCFT
      increases DCF recruitment. However, the ultrasonography test protocol did not
      identify differences in recruitment between deep and superficial neck muscles.
      The present study confirms the evidence that the CCFT challenges the cervical
      spine and that DCF activity is increased during this maneuver.

PMID- 19119395
TI  - Immediate Effects of Anterior-to-Posterior Talocrural Joint Mobilization after
      Prolonged Ankle Immobilization: A Preliminary Study.
AB  - Ankle dorsiflexion range of motion (ROM) typically decreases after prolonged
      immobilization. Anterior-to-posterior talocrural joint mobilizations are
      purported to increase dorsiflexion ROM and decrease joint stiffness after
      immobilization. The purpose of this study was to determine if a single bout of
      Grade III anterior-to-posterior talocrural joint mobilizations immediately
      affected measures of dorsiflexion ROM, posterior ankle joint stiffness, and
      posterior talar translation in ankles of patients who had been immobilized at
      least 14 days. Ten physically active patients (5 males, 5 females; age=21.4+/-3.3
      years) participated. Each had the ankle immobilized following a lower extremity
      injury for at least 14 days and presented with at least a 5 degrees dorsiflexion
      ROM deficit compared to the contralateral ankle. A crossover design was employed
      so that half of the subjects received joint mobilizations first and half of the
      subjects received the control intervention (no treatment) first. All subjects
      ultimately received both treatments. Active dorsiflexion ROM was assessed with a
      bubble inclinometer, and posterior ankle stiffness and talar translation were
      assessed with an instrumented ankle arthrometer. After a single application of
      grade III anterior-to-posterior talocrural joint mobilization, dorsiflexion ROM
      and posterior ankle joint stiffness were significantly increased. There was also
      a trend toward less posterior talar translation immediately after mobilization.
      The trend toward decreased posterior talar translation and increased posterior
      ankle joint stiffness supports the positional fault theory. Correction of an
      anterior talar positional fault offers a possible explanation for these results.

PMID- 19119394
TI  - The immediate effects of upper thoracic translatoric spinal manipulation on
      cervical pain and range of motion: a randomized clinical trial.
AB  - This study examined the effect of translatoric spinal manipulation (TSM) on
      cervical pain and cervical active motion restriction when applied to upper
      thoracic (T1-T4) segments. Active cervical rotation range of motion was measured
      re- and post-intervention with a cervical inclinometer (CROM), and cervical pain
      status was monitored before and after manipulation with a Faces Pain Scale. Study
      participants included a sample of convenience that included 32 patients referred
      to physical therapy with complaints of pain in the mid-cervical region and
      restricted active cervical rotation. Twenty-two patients were randomly assigned
      to the experimental group and ten were assigned to the control group. Pre- and
      post-intervention cervical range of motion and pain scale measurements were taken
      by a physical therapist assistant who was blinded to group assignment. The
      experimental group received TSM to hypomobile upper thoracic segments. The
      control group received no intervention. Paired t-tests were used to analyze
      within-group changes in cervical rotation and pain, and a 2-way repeated-measure
      ANOVA was used to analyze between-group differences in cervical rotation and
      pain. Significance was accepted at p = 0.05. Significant changes that exceeded
      the MDC(95) were detected for cervical rotation both within group and between
      groups with the TSM group demonstrating increased mean (SD) in right rotation of
      8.23 degrees (7.41 degrees ) and left rotation of 7.09 degrees (5.83 degrees ).
      Pain levels perceived during post-intervention cervical rotation showed
      significant improvement during right rotation for patients experiencing pain
      during bilateral rotation only (p=.05). This study supports the hypothesis that
      spinal manipulation applied to the upper thoracic spine (T1-T4 motion segments)
      significantly increases cervical rotation ROM and may reduce cervical pain at end
      range rotation for patients experiencing pain during bilateral cervical rotation.

PMID- 19119396
TI  - Changes in Clinical Parameters in Patients with Tension-type Headache Following
      Massage Therapy: A Pilot Study.
AB  - Complementary and alternative medicine approaches to treatment for tension-type
      headache are increasingly popular among patients, but evidence supporting its
      efficacy is limited. The objective of this study was to assess short term changes
      on primary and secondary headache pain measures in patients with tension-type
      headache (TTH) receiving a structured massage therapy program with a focus on
      myofascial trigger point therapy. Participants were enrolled in an open label
      trial using a baseline control with four 3-week phases: baseline, massage (two 3
      week phases) and follow-up. Twice weekly, 45-minute massage sessions commenced
      following the baseline phase. A daily headache diary was maintained throughout
      the study in which participants recorded headache incidence, intensity, and
      duration. The Headache Disability Index was administered upon study entry and at
      3-week intervals thereafter. 18 subjects were enrolled with 16 completing all
      headache diary, evaluation, and massage assignments. Study participants reported
      a median of 7.5 years with TTH. Headache frequency decreased from 4.7+/-0.7
      episodes per week during baseline to 3.7+/-0.9 during treatment period 2
      (P<0.001); reduction was also noted during the follow-up phase (3.2+/-1.0).
      Secondary measures of headache also decreased across the study phases with
      headache intensity decreasing by 30% (P<0.01) and headache duration from 4.0+/
      1.3 to 2.8+/-0.5 hours (P<0.05). A corresponding improvement in Headache
      Disability Index was found with massage (P<0.001). This pilot study provides
      preliminary evidence for reduction in headache pain and disability with massage
      therapy that targets myofascial trigger points, suggesting the need for more
      rigorously controlled studies.

PMID- 19119397
TI  - Variation in pelvic morphology may prevent the identification of anterior pelvic
      tilt.
AB  - Pelvic tilt is often quantified using the angle between the horizontal and a line
      connecting the anterior superior iliac spine (ASIS) and the posterior superior
      iliac spine (PSIS). Although this angle is determined by the balance of muscular
      and ligamentous forces acting between the pelvis and adjacent segments, it could
      also be influenced by variations in pelvic morphology. The primary objective of
      this anatomical study was to establish how such variation may affect the ASIS
      PSIS measure of pelvic tilt. In addition, we also investigated how variability in
      pelvic landmarks may influence measures of innominate rotational asymmetry and
      measures of pelvic height. Thirty cadaver pelves were used for the study. Each
      specimen was positioned in a fixed anatomical reference position and the angle
      between the ASIS and PSIS measured bilaterally. In addition, side-to-side
      differences in the height of the innominate bone were recorded. The study found a
      range of values for the ASIS-PSIS of 0-23 degrees, with a mean of 13 and standard
      deviation of 5 degrees. Asymmetry of pelvic landmarks resulted in side-to-side
      differences of up to 11 degrees in ASIS-PSIS tilt and 16 millimeters in
      innominate height. These results suggest that variations in pelvic morphology may
      significantly influence measures of pelvic tilt and innominate rotational
      asymmetry.

PMID- 19119398
TI  - "Three-dimensional movements of the sacroiliac joint: a systematic review of the
      literature and assessment of clinical utility" goode et Al. J man manip ther
      2008;16:25-38.

PMID- 19119399
TI  - Author response.

PMID- 19119400
TI  - Excellence is a Moving Target.

PMID- 19119401
TI  - Treatment of a patient with cervical radiculopathy using thoracic spine thrust
      manipulation, soft tissue mobilization, and exercise.
AB  - While there is currently little evidence to suggest which non-operative treatment
      approach is best for the management of patients with cervical radiculopathy,
      emerging evidence suggests that these patients benefit from a multimodal
      treatment approach. The purpose of this case report is to describe the physical
      therapy management of a patient with cervical radiculopathy. Diagnosis was based
      on the patient's meeting three of the four criteria in the diagnostic test
      cluster currently used to identify patients with cervical radiculopathy.
      Treatment included thrust manipulation of the thoracic spine, soft tissue
      mobilization, and therapeutic exercise. After three visits, patient-perceived
      disability, as measured by the Patient-Specific Functional Scale, improved from
      5/10 to 10/10. The Numeric Pain Rating Score decreased from 4.66/10 to 0/10. The
      patient rated his improvement as a very great deal better on the Global Rating of
      Change Scale. These clinically meaningful improvements were maintained at the 14
      week follow-up. While a cause-and-effect relationship may not be established from
      a case report, a multimodal approach including thoracic spine manipulation, soft
      tissue mobilization, and therapeutic exercise was associated with decreased pain
      and perceived disability in a patient with cervical radiculopathy. Further
      research is needed to investigate benefits of the components of this approach.

PMID- 19119402
TI  - Upper Limb Neural Tension and Seated Slump Tests: The False Positive Rate among
      Healthy Young Adults without Cervical or Lumbar Symptoms.
AB  - This study examined the false positive rate of the upper limb neural tension test
      (ULNTT) and seated slump test (SST) among healthy young adults with no history of
      cervical, lumbar, or peripheral symptoms. Eighty-four subjects (27 men and 57
      women) with a mean age of 22.9 years participated in the investigation. All
      participants completed a screening questionnaire designed to exclude subjects
      with a history of cervical or lumbar spine pain or injury, or upper or lower
      extremity neurological symptoms. The ULNTT and the SST were performed on the left
      upper and lower extremity of each participant. Of the 84 participants tested, 73
      (86.9%) were found to have a positive ULNTT at some point in the available range
      of elbow extension. Twenty-eight (33.3%) of the 84 subjects had a positive SST at
      some point in the available range of knee extension. The mean knee extension
      angle for those subjects with a positive SST was 15.1 degrees with a 95%
      confidence interval (CI) of 12.3 and 19.7 degrees . The mean elbow extension
      angle for those with a positive ULNTT was 49.4 degrees with a 95% CI of 44.8 and
      54.0 degrees . The number of positive tests for both the ULNTT and the SST was
      found to be high in this sample of asymptomatic healthy young adults. Based on
      the results of this investigation, the authors suggest that the current criteria
      for determining a positive test for both the ULNTT and the SST should be examined
      using the proposed range of motion cut-off scores.

PMID- 19119404
TI  - Evidence-based diagnosis and treatment of the painful sacroiliac joint.

PMID- 19119403
TI  - Evidence-based diagnosis and treatment of the painful sacroiliac joint.
AB  - Sacroiliac joint (SIJ) pain refers to the pain arising from the SIJ joint
      structures. SIJ dysfunction generally refers to aberrant position or movement of
      SIJ structures that may or may not result in pain. This paper aims to clarify the
      difference between these clinical concepts and present current available evidence
      regarding diagnosis and treatment of SIJ disorders. Tests for SIJ dysfunction
      generally have poor inter-examiner reliability. A reference standard for SIJ
      dysfunction is not readily available, so validity of the tests for this disorder
      is unknown. Tests that stress the SIJ in order to provoke familiar pain have
      acceptable inter-examiner reliability and have clinically useful validity against
      an acceptable reference standard. It is unknown if provocation tests can reliably
      identify extra-articular SIJ sources of pain. Three or more positive pain
      provocation SIJ tests have sensitivity and specificity of 91% and 78%,
      respectively. Specificity of three or more positive tests increases to 87% in
      patients whose symptoms cannot be made to move towards the spinal midline, i.e.,
      centralize. In chronic back pain populations, patients who have three or more
      positive provocation SIJ tests and whose symptoms cannot be made to centralize
      have a probability of having SIJ pain of 77%, and in pregnant populations with
      back pain, a probability of 89%. This combination of test findings could be used
      in research to evaluate the efficacy of specific treatments for SIJ pain.
      Treatments most likely to be effective are specific lumbopelvic stabilization
      training and injections of corticosteroid into the intra-articular space.

PMID- 19119405
TI  - Predictor Variables for a Positive Long-Term Functional Outcome in Patients with
      Acute and Chronic Neck and Back Pain Treated with a McKenzie Approach: A
      Secondary Analysis.
AB  - A cognitive behavioral approach was previously compared to a biomechanical
      approach (the McKenzie method) for the treatment of patients with back and neck
      pain in a randomized trial. Few differences between the treatment interventions
      were found. The aim of this secondary analysis was to determine if any clinical
      characteristics distinguished those patients who responded best to the McKenzie
      approach. Treatment success was defined as 50% reduction in original functional
      disability scores (Roland-Morris Disability Questionnaire or Northwick Park Neck
      Pain Questionnaire); failure to achieve this was defined as treatment failure. A
      liberal definition of success was 50% improvement retained at either 6 or 12
      months, whereas a strict definition of success was 50% improvement at both 6 and
      12 months. Ten variables were screened by univariate regression analysis to see
      if they predicted success. Any significant variables (P < 0.1) underwent multiple
      regression analysis. Only 21 and 16 patients out of 102 were deemed treatment
      successes according to the liberal and strict definitions, respectively. With the
      liberal definition, only centralization (P = 0.065), spine region (back rather
      than neck pain) (P = 0.089), and duration of pain (P = 0.001) emerged as
      predictors from the univariate regression analysis. With the strict definition,
      only the latter two variables emerged: spine region (P = 0.026) and duration of
      pain (P <0.01). All these variables were retained in the multiple regression
      analysis. In this study, duration of pain was the strongest predictor of success,
      although back pain and centralization had some predictive ability.

PMID- 19119406
TI  - "Potential pitfalls of clinical prediction rules" cook C. J man manip ther
      2008;16:69-71.

PMID- 19119407
TI  - Misguided guidelines for low back pain interventions.

PMID- 19119408
TI  - Questioning the ubiquity of neofunctionalization.
AB  - Gene duplication provides much of the raw material from which functional
      diversity evolves. Two evolutionary mechanisms have been proposed that generate
      functional diversity: neofunctionalization, the de novo acquisition of function
      by one duplicate, and subfunctionalization, the partitioning of ancestral
      functions between gene duplicates. With protein interactions as a surrogate for
      protein functions, evidence of prodigious neofunctionalization and
      subfunctionalization has been identified in analyses of empirical protein
      interactions and evolutionary models of protein interactions. However, we have
      identified three phenomena that have contributed to neofunctionalization being
      erroneously identified as a significant factor in protein interaction network
      evolution. First, self-interacting proteins are underreported in interaction data
      due to biological artifacts and design limitations in the two most common high
      throughput protein interaction assays. Second, evolutionary inferences have been
      drawn from paralog analysis without consideration for concurrent and subsequent
      duplication events. Third, the theoretical model of prodigious
      neofunctionalization is unable to reproduce empirical network clustering and
      relies on untenable parameter requirements. In light of these findings, we
      believe that protein interaction evolution is more persuasively characterized by
      subfunctionalization and self-interactions.

PMID- 19119409
TI  - Polyamine sharing between tubulin dimers favours microtubule nucleation and
      elongation via facilitated diffusion.
AB  - We suggest for the first time that the action of multivalent cations on
      microtubule dynamics can result from facilitated diffusion of GTP-tubulin to the
      microtubule ends. Facilitated diffusion can promote microtubule assembly,
      because, upon encountering a growing nucleus or the microtubule wall, random GTP
      tubulin sliding on their surfaces will increase the probability of association to
      the target sites (nucleation sites or MT ends). This is an original explanation
      for understanding the apparent discrepancy between the high rate of microtubule
      elongation and the low rate of tubulin association at the microtubule ends in the
      viscous cytoplasm. The mechanism of facilitated diffusion requires an attraction
      force between two tubulins, which can result from the sharing of multivalent
      counterions. Natural polyamines (putrescine, spermidine, and spermine) are
      present in all living cells and are potent agents to trigger tubulin self
      attraction. By using an analytical model, we analyze the implication of
      facilitated diffusion mediated by polyamines on nucleation and elongation of
      microtubules. In vitro experiments using pure tubulin indicate that the promotion
      of microtubule assembly by polyamines is typical of facilitated diffusion. The
      results presented here show that polyamines can be of particular importance for
      the regulation of the microtubule network in vivo and provide the basis for
      further investigations into the effects of facilitated diffusion on cytoskeleton
      dynamics.

PMID- 19119410
TI  - Shape, size, and robustness: feasible regions in the parameter space of
      biochemical networks.
AB  - The concept of robustness of regulatory networks has received much attention in
      the last decade. One measure of robustness has been associated with the volume of
      the feasible region, namely, the region in the parameter space in which the
      system is functional. In this paper, we show that, in addition to volume, the
      geometry of this region has important consequences for the robustness and the
      fragility of a network. We develop an approximation within which we could
      algebraically specify the feasible region. We analyze the segment polarity gene
      network to illustrate our approach. The study of random walks in the parameter
      space and how they exit the feasible region provide us with a rich perspective on
      the different modes of failure of this network model. In particular, we found
      that, between two alternative ways of activating Wingless, one is more robust
      than the other. Our method provides a more complete measure of robustness to
      parameter variation. As a general modeling strategy, our approach is an
      interesting alternative to Boolean representation of biochemical networks.

PMID- 19119411
TI  - Predicting cellular growth from gene expression signatures.
AB  - Maintaining balanced growth in a changing environment is a fundamental systems
      level challenge for cellular physiology, particularly in microorganisms. While
      the complete set of regulatory and functional pathways supporting growth and
      cellular proliferation are not yet known, portions of them are well understood.
      In particular, cellular proliferation is governed by mechanisms that are highly
      conserved from unicellular to multicellular organisms, and the disruption of
      these processes in metazoans is a major factor in the development of cancer. In
      this paper, we develop statistical methodology to identify quantitative aspects
      of the regulatory mechanisms underlying cellular proliferation in Saccharomyces
      cerevisiae. We find that the expression levels of a small set of genes can be
      exploited to predict the instantaneous growth rate of any cellular culture with
      high accuracy. The predictions obtained in this fashion are robust to changing
      biological conditions, experimental methods, and technological platforms. The
      proposed model is also effective in predicting growth rates for the related yeast
      Saccharomyces bayanus and the highly diverged yeast Schizosaccharomyces pombe,
      suggesting that the underlying regulatory signature is conserved across a wide
      range of unicellular evolution. We investigate the biological significance of the
      gene expression signature that the predictions are based upon from multiple
      perspectives: by perturbing the regulatory network through the Ras/PKA pathway,
      observing strong upregulation of growth rate even in the absence of appropriate
      nutrients, and discovering putative transcription factor binding sites, observing
      enrichment in growth-correlated genes. More broadly, the proposed methodology
      enables biological insights about growth at an instantaneous time scale,
      inaccessible by direct experimental methods. Data and tools enabling others to
      apply our methods are available at http://function.princeton.edu/growthrate.

PMID- 19119412
TI  - Neuropeptide Y gene polymorphisms confer risk of early-onset atherosclerosis.
AB  - Neuropeptide Y (NPY) is a strong candidate gene for coronary artery disease
      (CAD). We have previously identified genetic linkage to familial CAD in the
      genomic region of NPY. We performed follow-up genetic, biostatistical, and
      functional analysis of NPY in early-onset CAD. In familial CAD (GENECARD, N = 420
      families), we found increased microsatellite linkage to chromosome 7p14 (OSA LOD
      = 4.2, p = 0.004) in 97 earliest age-of-onset families. Tagged NPY SNPs
      demonstrated linkage to CAD of a 6-SNP block (LOD = 1.58-2.72), family-based
      association of this block with CAD (p = 0.02), and stronger linkage to CAD in the
      earliest age-of-onset families. Association of this 6-SNP block with CAD was
      validated in: (a) 556 non-familial early-onset CAD cases and 256 controls (OR
      1.46-1.65, p = 0.01-0.05), showing stronger association in youngest cases (OR
      1.84-2.20, p = 0.0004-0.09); and (b) GENECARD probands versus non-familial
      controls (OR 1.79-2.06, p = 0.003-0.02). A promoter SNP (rs16147) within this 6
      SNP block was associated with higher plasma NPY levels (p = 0.04). To assess a
      causal role of NPY in atherosclerosis, we applied the NPY1-receptor-antagonist
      BIBP-3226 adventitially to endothelium-denuded carotid arteries of apolipoprotein
      E-deficient mice; treatment reduced atherosclerotic neointimal area by 50% (p =
      0.03). Thus, NPY variants associate with atherosclerosis in two independent
      datasets (with strong age-of-onset effects) and show allele-specific expression
      with NPY levels, while NPY receptor antagonism reduces atherosclerosis in mice.
      We conclude that NPY contributes to atherosclerosis pathogenesis.

PMID- 19119413
TI  - Regulation of small RNA accumulation in the maize shoot apex.
AB  - MicroRNAs (miRNAs) and trans-acting siRNAs (ta-siRNAs) are essential to the
      establishment of adaxial-abaxial (dorsoventral) leaf polarity. Tas3-derived ta
      siRNAs define the adaxial side of the leaf by restricting the expression domain
      of miRNA miR166, which in turn demarcates the abaxial side of leaves by
      restricting the expression of adaxial determinants. To investigate the regulatory
      mechanisms that allow for the precise spatiotemporal accumulation of these
      polarizing small RNAs, we used laser-microdissection coupled to RT-PCR to
      determine the expression profiles of their precursor transcripts within the maize
      shoot apex. Our data reveal that the pattern of mature miR166 accumulation
      results, in part, from intricate transcriptional regulation of its precursor loci
      and that only a subset of mir166 family members contribute to the establishment
      of leaf polarity. We show that miR390, an upstream determinant in leaf polarity
      whose activity triggers tas3 ta-siRNA biogenesis, accumulates adaxially in
      leaves. The polar expression of miR390 is established and maintained independent
      of the ta-siRNA pathway. The comparison of small RNA localization data with the
      expression profiles of precursor transcripts suggests that miR166 and miR390
      accumulation is also regulated at the level of biogenesis and/or stability.
      Furthermore, mir390 precursors accumulate exclusively within the epidermal layer
      of the incipient leaf, whereas mature miR390 accumulates in sub-epidermal layers
      as well. Regulation of miR390 biogenesis, stability, or even discrete trafficking
      of miR390 from the epidermis to underlying cell layers provide possible
      mechanisms that define the extent of miR390 accumulation within the incipient
      leaf, which patterns this small field of cells into adaxial and abaxial domains
      via the production of tas3-derived ta-siRNAs.

PMID- 19119414
TI  - IL2RA genetic heterogeneity in multiple sclerosis and type 1 diabetes
      susceptibility and soluble interleukin-2 receptor production.
AB  - Multiple sclerosis (MS) and type 1 diabetes (T1D) are organ-specific autoimmune
      disorders with significant heritability, part of which is conferred by shared
      alleles. For decades, the Human Leukocyte Antigen (HLA) complex was the only
      known susceptibility locus for both T1D and MS, but loci outside the HLA complex
      harboring risk alleles have been discovered and fully replicated. A genome-wide
      association scan for MS risk genes and candidate gene association studies have
      previously described the IL2RA gene region as a shared autoimmune locus. In order
      to investigate whether autoimmunity risk at IL2RA was due to distinct or shared
      alleles, we performed a genetic association study of three IL2RA variants in a
      DNA collection of up to 9,407 healthy controls, 2,420 MS, and 6,425 T1D subjects
      as well as 1,303 MS parent/child trios. Here, we report "allelic heterogeneity"
      at the IL2RA region between MS and T1D. We observe an allele associated with
      susceptibility to one disease and risk to the other, an allele that confers
      susceptibility to both diseases, and an allele that may only confer
      susceptibility to T1D. In addition, we tested the levels of soluble interleukin-2
      receptor (sIL-2RA) in the serum from up to 69 healthy control subjects, 285 MS,
      and 1,317 T1D subjects. We demonstrate that multiple variants independently
      correlate with sIL-2RA levels.

PMID- 19119415
TI  - Instability of plastid DNA in the nuclear genome.
AB  - Functional gene transfer from the plastid (chloroplast) and mitochondrial genomes
      to the nucleus has been an important driving force in eukaryotic evolution. Non
      functional DNA transfer is far more frequent, and the frequency of such transfers
      from the plastid to the nucleus has been determined experimentally in tobacco
      using transplastomic lines containing, in their plastid genome, a kanamycin
      resistance gene (neo) readymade for nuclear expression. Contrary to expectations,
      non-Mendelian segregation of the kanamycin resistance phenotype is seen in
      progeny of some lines in which neo has been transferred to the nuclear genome.
      Here, we provide a detailed analysis of the instability of kanamycin resistance
      in nine of these lines, and we show that it is due to deletion of neo. Four lines
      showed instability with variation between progeny derived from different areas of
      the same plant, suggesting a loss of neo during somatic cell division. One line
      showed a consistent reduction in the proportion of kanamycin-resistant progeny,
      suggesting a loss of neo during meiosis, and the remaining four lines were
      relatively stable. To avoid genomic enlargement, the high frequency of plastid
      DNA integration into the nuclear genome necessitates a counterbalancing removal
      process. This is the first demonstration of such loss involving a high proportion
      of recent nuclear integrants. We propose that insertion, deletion, and
      rearrangement of plastid sequences in the nuclear genome are important
      evolutionary processes in the generation of novel nuclear genes. This work is
      also relevant in the context of transgenic plant research and crop production,
      because similar processes to those described here may be involved in the loss of
      plant transgenes.

PMID- 19119416
TI  - Non-coding RNA prediction and verification in Saccharomyces cerevisiae.
AB  - Non-coding RNA (ncRNA) play an important and varied role in cellular function. A
      significant amount of research has been devoted to computational prediction of
      these genes from genomic sequence, but the ability to do so has remained elusive
      due to a lack of apparent genomic features. In this work, thermodynamic stability
      of ncRNA structural elements, as summarized in a Z-score, is used to predict
      ncRNA in the yeast Saccharomyces cerevisiae. This analysis was coupled with
      comparative genomics to search for ncRNA genes on chromosome six of S. cerevisiae
      and S. bayanus. Sets of positive and negative control genes were evaluated to
      determine the efficacy of thermodynamic stability for discriminating ncRNA from
      background sequence. The effect of window sizes and step sizes on the sensitivity
      of ncRNA identification was also explored. Non-coding RNA gene candidates, common
      to both S. cerevisiae and S. bayanus, were verified using northern blot analysis,
      rapid amplification of cDNA ends (RACE), and publicly available cDNA library
      data. Four ncRNA transcripts are well supported by experimental data (RUF10,
      RUF11, RUF12, RUF13), while one additional putative ncRNA transcript is well
      supported but the data are not entirely conclusive. Six candidates appear to be
      structural elements in 5' or 3' untranslated regions of annotated protein-coding
      genes. This work shows that thermodynamic stability, coupled with comparative
      genomics, can be used to predict ncRNA with significant structural elements.

PMID- 19119417
TI  - Quantitative models of in vitro bacteriophage-host dynamics and their application
      to phage therapy.
AB  - Phage therapy is the use of bacteriophages as antimicrobial agents for the
      control of pathogenic and other problem bacteria. It has previously been argued
      that successful application of phage therapy requires a good understanding of the
      non-linear kinetics of phage-bacteria interactions. Here we combine experimental
      and modelling approaches to make a detailed examination of such kinetics for the
      important food-borne pathogen Campylobacter jejuni and a suitable virulent phage
      in an in vitro system. Phage-insensitive populations of C. jejuni arise readily,
      and as far as we are aware this is the first phage therapy study to test, against
      in vitro data, models for phage-bacteria interactions incorporating phage
      insensitive or resistant bacteria. We find that even an apparently simplistic
      model fits the data surprisingly well, and we confirm that the so-called
      inundation and proliferation thresholds are likely to be of considerable
      practical importance to phage therapy. We fit the model to time series data in
      order to estimate thresholds and rate constants directly. A comparison of the fit
      for each culture reveals density-dependent features of phage infectivity that are
      worthy of further investigation. Our results illustrate how insight from
      empirical studies can be greatly enhanced by the use of kinetic models: such
      combined studies of in vitro systems are likely to be an essential precursor to
      building a meaningful picture of the kinetic properties of in vivo phage therapy.

PMID- 19119418
TI  - Positive selection results in frequent reversible amino acid replacements in the
      G protein gene of human respiratory syncytial virus.
AB  - Human respiratory syncytial virus (HRSV) is the major cause of lower respiratory
      tract infections in children under 5 years of age and the elderly, causing annual
      disease outbreaks during the fall and winter. Multiple lineages of the HRSVA and
      HRSVB serotypes co-circulate within a single outbreak and display a strongly
      temporal pattern of genetic variation, with a replacement of dominant genotypes
      occurring during consecutive years. In the present study we utilized phylogenetic
      methods to detect and map sites subject to adaptive evolution in the G protein of
      HRSVA and HRSVB. A total of 29 and 23 amino acid sites were found to be
      putatively positively selected in HRSVA and HRSVB, respectively. Several of these
      sites defined genotypes and lineages within genotypes in both groups, and
      correlated well with epitopes previously described in group A. Remarkably, 18 of
      these positively selected tended to revert in time to a previous codon state,
      producing a "flip-flop" phylogenetic pattern. Such frequent evolutionary
      reversals in HRSV are indicative of a combination of frequent positive selection,
      reflecting the changing immune status of the human population, and a limited
      repertoire of functionally viable amino acids at specific amino acid sites.

PMID- 19119419
TI  - An upstream open reading frame controls translation of var2csa, a gene implicated
      in placental malaria.
AB  - Malaria, caused by the parasite Plasmodium falciparum, is responsible for
      substantial morbidity, mortality and economic losses in tropical regions of the
      world. Pregnant women are exceptionally vulnerable to severe consequences of the
      infection, due to the specific adhesion of parasite-infected erythrocytes in the
      placenta. This adhesion is mediated by a unique variant of PfEMP1, a parasite
      encoded, hyper-variable antigen placed on the surface of infected cells. This
      variant, called VAR2CSA, binds to chondroitin sulfate A on syncytiotrophoblasts
      in the intervillous space of placentas. VAR2CSA appears to only be expressed in
      the presence of a placenta, suggesting that its expression is actively repressed
      in men, children or non-pregnant women; however, the mechanism of repression is
      not understood. Using cultured parasite lines and reporter gene constructs, we
      show that the gene encoding VAR2CSA contains a small upstream open reading frame
      that acts to repress translation of the resulting mRNA, revealing a novel form of
      gene regulation in malaria parasites. The mechanism underlying this translational
      repression is reversible, allowing high levels of protein translation upon
      selection, thus potentially enabling parasites to upregulate expression of this
      variant antigen in the presence of the appropriate host tissue.

PMID- 19119420
TI  - Transmission of influenza virus in a mammalian host is increased by PB2 amino
      acids 627K or 627E/701N.
AB  - Since 2003, more than 380 cases of H5N1 influenza virus infection of humans have
      been reported. Although the resultant disease in these cases was often severe or
      fatal, transmission of avian influenza viruses between humans is rare. The
      precise nature of the barrier blocking human-to-human spread is unknown. It is
      clear, however, that efficient human-to-human transmission of an antigenically
      novel influenza virus would result in a pandemic. Influenza viruses with changes
      at amino acids 627 or 701 of the PB2 protein have been isolated from human cases
      of highly pathogenic H5 and H7 avian influenza. Herein, we have used the guinea
      pig model to test the contributions of PB2 627 and 701 to mammalian transmission.
      To this end, viruses carrying mutations at these positions were generated in the
      A/Panama/2007/99 (H3N2) and A/Viet Nam/1203/04 (H5N1) backgrounds. In the context
      of either rPan99 or rVN1203, mutation of lysine 627 to the avian consensus
      residue glutamic acid was found to decrease transmission. Introduction of an
      asparagine at position 701, in conjunction with the K627E mutation, resulted in a
      phenotype more similar to that of the parental strains, suggesting that this
      residue can compensate for the lack of 627K in terms of increasing transmission
      in mammals. Thus, our data show that PB2 amino acids 627 and 701 are determinants
      of mammalian inter-host transmission in diverse virus backgrounds.

PMID- 19119421
TI  - The Epstein-Barr virus G-protein-coupled receptor contributes to immune evasion
      by targeting MHC class I molecules for degradation.
AB  - Epstein-Barr virus (EBV) is a human herpesvirus that persists as a largely
      subclinical infection in the vast majority of adults worldwide. Recent evidence
      indicates that an important component of the persistence strategy involves active
      interference with the MHC class I antigen processing pathway during the lytic
      replication cycle. We have now identified a novel role for the lytic cycle gene,
      BILF1, which encodes a glycoprotein with the properties of a constitutive
      signaling G-protein-coupled receptor (GPCR). BILF1 reduced the levels of MHC
      class I at the cell surface and inhibited CD8(+) T cell recognition of endogenous
      target antigens. The underlying mechanism involves physical association of BILF1
      with MHC class I molecules, an increased turnover from the cell surface, and
      enhanced degradation via lysosomal proteases. The BILF1 protein of the closely
      related CeHV15 gamma(1)-herpesvirus of the Rhesus Old World primate (80% amino
      acid sequence identity) downregulated surface MHC class I similarly to EBV BILF1.
      Amongst the human herpesviruses, the GPCR encoded by the ORF74 of the KSHV
      gamma(2)-herpesvirus is most closely related to EBV BILF1 (15% amino acid
      sequence identity) but did not affect levels of surface MHC class I. An
      engineered mutant of BILF1 that was unable to activate G protein signaling
      pathways retained the ability to downregulate MHC class I, indicating that the
      immune-modulating and GPCR-signaling properties are two distinct functions of
      BILF1. These findings extend our understanding of the normal biology of an
      important human pathogen. The discovery of a third EBV lytic cycle gene that
      cooperates to interfere with MHC class I antigen processing underscores the
      importance of the need for EBV to be able to evade CD8(+) T cell responses during
      the lytic replication cycle, at a time when such a large number of potential
      viral targets are expressed.

PMID- 19119422
TI  - A novel role for Mc1r in the parallel evolution of depigmentation in independent
      populations of the cavefish Astyanax mexicanus.
AB  - The evolution of degenerate characteristics remains a poorly understood
      phenomenon. Only recently has the identification of mutations underlying
      regressive phenotypes become accessible through the use of genetic analyses.
      Focusing on the Mexican cave tetra Astyanax mexicanus, we describe, here, an
      analysis of the brown mutation, which was first described in the literature
      nearly 40 years ago. This phenotype causes reduced melanin content, decreased
      melanophore number, and brownish eyes in convergent cave forms of A. mexicanus.
      Crosses demonstrate non-complementation of the brown phenotype in F(2)
      individuals derived from two independent cave populations: Pachon and the linked
      Yerbaniz and Japones caves, indicating the same locus is responsible for reduced
      pigmentation in these fish. While the brown mutant phenotype arose prior to the
      fixation of albinism in Pachon cave individuals, it is unclear whether the brown
      mutation arose before or after the fixation of albinism in the linked
      Yerbaniz/Japones caves. Using a QTL approach combined with sequence and
      functional analyses, we have discovered that two distinct genetic alterations in
      the coding sequence of the gene Mc1r cause reduced pigmentation associated with
      the brown mutant phenotype in these caves. Our analysis identifies a novel role
      for Mc1r in the evolution of degenerative phenotypes in blind Mexican cavefish.
      Further, the brown phenotype has arisen independently in geographically separate
      caves, mediated through different mutations of the same gene. This example of
      parallelism indicates that certain genes are frequent targets of mutation in the
      repeated evolution of regressive phenotypes in cave-adapted species.

PMID- 19119423
TI  - Adaptive evolution in zinc finger transcription factors.
AB  - The majority of human genes are conserved among mammals, but some gene families
      have undergone extensive expansion in particular lineages. Here, we present an
      evolutionary analysis of one such gene family, the poly-zinc-finger (poly-ZF)
      genes. The human genome encodes approximately 700 members of the poly-ZF family
      of putative transcriptional repressors, many of which have associated KRAB, SCAN,
      or BTB domains. Analysis of the gene family across the tree of life indicates
      that the gene family arose from a small ancestral group of eukaryotic zinc-finger
      transcription factors through many repeated gene duplications accompanied by
      functional divergence. The ancestral gene family has probably expanded
      independently in several lineages, including mammals and some fishes.
      Investigation of adaptive evolution among recent paralogs using d(N)/d(S)
      analysis indicates that a major component of the selective pressure acting on
      these genes has been positive selection to change their DNA-binding specificity.
      These results suggest that the poly-ZF genes are a major source of new
      transcriptional repression activity in humans and other primates.

PMID- 19119424
TI  - The cell adhesion molecule "CAR" and sialic acid on human erythrocytes influence
      adenovirus in vivo biodistribution.
AB  - Although it has been known for 50 years that adenoviruses (Ads) interact with
      erythrocytes ex vivo, the molecular and structural basis for this interaction,
      which has been serendipitously exploited for diagnostic tests, is unknown. In
      this study, we characterized the interaction between erythrocytes and unrelated
      Ad serotypes, human 5 (HAd5) and 37 (HAd37), and canine 2 (CAV-2). While these
      serotypes agglutinate human erythrocytes, they use different receptors, have
      different tropisms and/or infect different species. Using molecular, biochemical,
      structural and transgenic animal-based analyses, we found that the primary
      erythrocyte interaction domain for HAd37 is its sialic acid binding site, while
      CAV-2 binding depends on at least three factors: electrostatic interactions,
      sialic acid binding and, unexpectedly, binding to the coxsackievirus and
      adenovirus receptor (CAR) on human erythrocytes. We show that the presence of CAR
      on erythrocytes leads to prolonged in vivo blood half-life and significantly
      reduced liver infection when a CAR-tropic Ad is injected intravenously. This
      study provides i) a molecular and structural rationale for Ad-erythrocyte
      interactions, ii) a basis to improve vector-mediated gene transfer and iii) a
      mechanism that may explain the biodistribution and pathogenic inconsistencies
      found between human and animal models.

PMID- 19119425
TI  - ATR and Chk1 suppress a caspase-3-dependent apoptotic response following DNA
      replication stress.
AB  - The related PIK-like kinases Ataxia-Telangiectasia Mutated (ATM) and ATM- and
      Rad3-related (ATR) play major roles in the regulation of cellular responses to
      DNA damage or replication stress. The pro-apoptotic role of ATM and p53 in
      response to ionizing radiation (IR) has been widely investigated. Much less is
      known about the control of apoptosis following DNA replication stress. Recent
      work indicates that Chk1, the downstream phosphorylation target of ATR, protects
      cells from apoptosis induced by DNA replication inhibitors as well as IR. The aim
      of the work reported here was to determine the roles of ATM- and ATR-protein
      kinase cascades in the control of apoptosis following replication stress and the
      relationship between Chk1-suppressed apoptotic pathways responding to replication
      stress or IR. ATM and ATR/Chk1 signalling pathways were manipulated using siRNA
      mediated depletions or specific inhibitors in two tumour cell lines or
      fibroblasts derived from patients with inherited mutations. We show that
      depletion of ATM or its downstream phosphorylation targets, NBS1 and BID, has
      relatively little effect on apoptosis induced by DNA replication inhibitors,
      while ATR or Chk1 depletion strongly enhances cell death induced by such agents
      in all cells tested. Furthermore, early events occurring after the disruption of
      DNA replication (accumulation of RPA foci and RPA34 hyperphosphorylation) in ATR-
      or Chk1-depleted cells committed to apoptosis are not detected in ATM-depleted
      cells. Unlike the Chk1-suppressed pathway responding to IR, the replication
      stress-triggered apoptotic pathway did not require ATM and is characterized by
      activation of caspase 3 in both p53-proficient and -deficient cells. Taken
      together, our results show that the ATR-Chk1 signalling pathway plays a major
      role in the regulation of death in response to DNA replication stress and that
      the Chk1-suppressed pathway protecting cells from replication stress is clearly
      distinguishable from that protecting cells from IR.

PMID- 19119426
TI  - Cohabitation and children's living arrangements: New estimates from the United
      States.
AB  - This paper uses the 1995 and 2002 waves of the National Survey of Family Growth
      to examine recent trends in cohabitation in the United States. We find increases
      in both the prevalence and duration of unmarried cohabitation. Cohabitation
      continues to transform children's family lives, as children are increasingly born
      to cohabiting mothers (18% during 1997-2001) or later experience their mother's
      entry into a cohabiting union. Consequently, we estimate that two-fifths of all
      children spend some time in a cohabiting family by age 12. Because of substantial
      missing data in the 2002 NSFG, we are unable to produce new estimates of divorce
      or of children's time in single-parent families. Nonetheless, our results point
      to the steady growth of cohabitation and to the evolving role of cohabitation in
      U.S. family life.

PMID- 19119428
TI  - Comparison of statistical data models for identifying differentially expressed
      genes using a generalized likelihood ratio test.
AB  - Currently, statistical techniques for analysis of microarray-generated data sets
      have deficiencies due to limited understanding of errors inherent in the data. A
      generalized likelihood ratio (GLR) test based on an error model has been recently
      proposed to identify differentially expressed genes from microarray experiments.
      However, the use of different error structures under the GLR test has not been
      evaluated, nor has this method been compared to commonly used statistical tests
      such as the parametric t-test. The concomitant effects of varying data signal-to
      noise ratio and replication number on the performance of statistical tests also
      remain largely unexplored. In this study, we compared the effects of different
      underlying statistical error structures on the GLR test's power in identifying
      differentially expressed genes in microarray data. We evaluated such variants of
      the GLR test as well as the one sample t-test based on simulated data by means of
      receiver operating characteristic (ROC) curves. Further, we used bootstrapping of
      ROC curves to assess statistical significance of differences between the areas
      under the curves. Our results showed that i) the GLR tests outperformed the t
      test for detecting differential gene expression, ii) the identity of the
      underlying error structure was important in determining the GLR tests'
      performance, and iii) signal-to-noise ratio was a more important contributor than
      sample replication in identifying statistically significant differential gene
      expression.

PMID- 19119427
TI  - Transcription initiation by mix and match elements: flexibility for polymerase
      binding to bacterial promoters.
AB  - Bacterial RNA polymerase is composed of a core of subunits (beta, beta', alpha1,
      alpha2, omega), which have RNA synthesizing activity, and a specificity factor
      (sigma), which identifies the start of transcription by recognizing and binding
      to sequences elements within promoter DNA. Four core promoter consensus
      sequences, the -10 element, the extended -10 (TGn) element, the -35 element, and
      the UP elements, have been known for many years; the importance of a nontemplate
      G at position -5 has been recognized more recently. However, the functions of
      these elements are not the same. The AT-rich UP elements, the -35 elements ((
      35)TTGACA(-30)), and the extended -10 ((-15)TGn(-13)) are recognized as double
      stranded binding elements, whereas the -5 nontemplate G is recognized in the
      context of single-stranded DNA at the transcription bubble. Furthermore, the -10
      element ((-12)TATAAT(-7)) is recognized as both double strand DNA for the T:A bp
      at position -12 and as nontemplate, single-strand DNA from positions -11 to -7.
      The single-strand sequences at positions -11 to -7 as well as the -5 contribute
      to later steps in transcription initiation that involve isomerization of
      polymerase and separation of the promoter DNA around the transcription start
      site. Recent work has demonstrated that the double strand elements may be used in
      various combinations to yield an effective promoter. Thus, while some minimal
      number of contacts is required for promoter function, polymerase allows the
      elements to be mixed and matched. Interestingly, which particular elements are
      used does not appear to fundamentally alter the transcription bubble generated in
      the stable complex. In this review, we discuss the multiple steps involved in
      forming a transcriptionally competent polymerase/promoter complex, and we examine
      what is known about polymerase recognition of core promoter elements. We suggest
      that considering promoter elements according to their involvement in early
      (polymerase binding) or later (polymerase isomerization) steps in transcription
      initiation rather than simply from their match to conventional promoter consensus
      sequences is a more instructive form of promoter classification.

PMID- 19119429
TI  - Brain-derived neurotrophic factor and autism: maternal and infant peripheral
      blood levels in the Early Markers for Autism (EMA) Study.
AB  - To investigate levels of brain-derived neurotrophic factor (BDNF) in mid
      pregnancy and neonatal blood specimens as early biologic markers for autism, we
      conducted a population-based case-control study nested within the cohort of
      infants born from July 2000 to September 2001 to women who participated in the
      prenatal screening program in Orange County, CA. Cases (n=84) were all children
      receiving services for autism at the Regional Center of Orange County. Two
      comparison groups from the same study population were included: children with
      mental retardation or developmental delay (n=49) receiving services at the same
      regional center, and children not receiving services for developmental
      disabilities, randomly sampled from the California birth certificate files
      (n=159), and frequency matched to autism cases on sex, birth year, and birth
      month. BDNF concentrations were measured in archived mid-pregnancy and neonatal
      blood specimens drawn during routine prenatal and newborn screening using a
      highly sensitive bead-based assay (Luminex, Biosource Human BDNF Antibody Bead
      Kit, Invitrogen-Biosource, Carlsbad, CA). The concentration of BDNF in maternal
      mid-pregnancy and neonatal specimens was similar across all three study groups.
      These data do not support previous findings of an association between BDNF and
      autism and suggest that the concentration of BDNF during critical periods of
      early neurodevelopment is not likely to be a useful biomarker for autism
      susceptibility.

PMID- 19119431
TI  - Immunogenicity and safety of two different Haemophilus influenzae type b
      conjugate vaccines in Korean infants.
AB  - The incidence of invasive diseases, including meningitis caused by Haemophilus
      influenzae type b (Hib) was markedly decreased after routine immunization of Hib
      vaccine through diverse schedules in many countries. The purpose of this study
      was to evaluate the immunogenicity and safety of Hib conjugate vaccines in Korean
      children before the implementation of a national immunization program against Hib
      in Korea. A multicenter controlled trial was performed on two different Hib
      vaccines in Korean children. A total of 319 infants were enrolled: 199 infants
      were immunized with the Hib polysaccharide conjugated to the tetanus toxoid (PRP
      T) and 120 infants with the Hib polysaccharide conjugated to the outer-membrane
      protein of Neisseria meningitides (PRP-OMP). Immunogenicity was evaluated by
      enzyme-linked immunosorbent assay (ELISA) and serum bactericidal assay. Both
      vaccines showed good immunologic responses after primary immunization. After 2
      doses of PRP-T or PRP-OMP, 78.9% and 91.7% of infants achieved an antibody level
      of >or=1.0 microg/mL, respectively. Both vaccines were safe and well-tolerated.
      No serious adverse events were observed. Thus, Hib conjugate vaccines appear to
      be safe and show good immunogenicity in Korean infants. These results will be
      important reference data for the implementation of Hib vaccine in the national
      immunization program of Korea.

PMID- 19119432
TI  - Coinfection of viral agents in Korean children with acute watery diarrhea.
AB  - Currently, there are a few reports on viral coinfection that causes an acute
      watery diarrhea in Korean children. So, to evaluate the features of coinfectious
      viral agents in children with acute watery diarrhea, we enrolled 155 children
      with acute watery diarrhea from July 2005 to June 2006. Fecal samples were
      collected and evaluated for various viral infections such as rotavirus,
      norovirus, adenovirus and astrovirus. The mean (+/-standard deviation) age of the
      children was 2.71+/-2.37 yr. The detection rate of viral agents was most common
      in children between the ages of 1 and 3 yr. Rotavirus was detected in 63 children
      (41.3%), norovirus in 56 (36.2%), adenovirus in 11 (7.1%), and astrovirus in 1
      (0.6%). Regarding rotavirus, there were 38 (60.3%) cases with monoinfection and
      25 (39.7%) with coinfection. For norovirus, there were 33 (58.9%) cases with
      monoinfection and 23 (41.1%) with coinfection. Coinfection with rotavirus and
      norovirus was most common, and occurred in 20/155 cases (12.9%) including
      coinfection with adenovirus. So, rotavirus and norovirus were the most common
      coinfectious viral agents in our study population with acute watery diarrhea.

PMID- 19119433
TI  - Current antimicrobial usage for the management of neutropenic fever in Korea: a
      nationwide survey.
AB  - A nationwide questionnaire-based survey was performed to evaluate the current
      clinical practices for the management of neutropenic fever in hematology units
      and hematopoietic stem cell transplantation (HSCT) centers throughout Korea. A
      86.9% response rate was obtained from a total of 46 doctors and practical
      policies of the 33 sites were analysed. Approximately 42.4% and 84.8% of the
      sites responded that they used oral fluoroquinolone as prophylaxis for
      neutropenic patients receiving chemotherapy and HSCT, respectively. Additionally,
      42.4% of the sites responded that they used antifungal prophylaxis in the
      chemotherapy groups whereas 90.9% of the sites responded that they used
      antifungal prophylaxis in HSCT recipients. Approximately half of the responding
      sites prescribed combination regimen with 3rd or 4th cephalosporin plus
      aminoglycoside as a first-line therapy. Most of the sites considered persistent
      fever for 2-4 days or aggravated clinical symptoms for 1-2 days as failure of the
      first-line regimen, and they changed antibiotics to second-line regimens that
      varied widely among the sites. Twenty-seven sites (84.4%) responded that they
      considered adding an antifungal agent when fever persisted for 5-7 days despite
      antibacterial therapy. Amphotericin B deoxycholate was preferred as a first-line
      antifungal, which was probably due to the limitations of the national health
      insurance system. The role of oral antibiotics in the management of neutropenic
      fever still accounted for a small portion. To the best of our knowledge, this
      survey is the first report to examine the practical policies currently in place
      for the management of neutropenic fever in Korea and the results of this survey
      may help to establish a Korean guideline in the future.

PMID- 19119434
TI  - Characteristics of mechanical ventilation employed in intensive care units: a
      multicenter survey of hospitals.
AB  - A 1D point-prevalence study was performed to describe the characteristics of
      conventional mechanical ventilation in intensive care units (ICUs). In addition,
      a survey was conducted to determine the characteristics of ICUs. A prospective,
      multicenter study was performed in ICUs at 24 university hospitals. The study
      population consisted of 223 patients who were receiving mechanical ventilation or
      had been weaned off mechanical ventilation within the past 24 hr. Common
      indications for the initiation of mechanical ventilation included acute
      respiratory failure (66%), acute exacerbation of chronic respiratory failure
      (15%) (including tuberculosis-destroyed lung [5%]), coma (13%), and neuromuscular
      disorders (6%). Mechanical ventilation was delivered via an endotracheal tube in
      68% of the patients, tracheostomy in 28% and facial mask with noninvasive
      ventilation (NIV) in 4%. NIV was used in 2 centers. In patients who had undergone
      tracheostomy, the procedure had been performed 16.9+/-8.1 days after intubation.
      Intensivists treated 29% of the patients. A need for additional educational
      programs regarding clinical practice in the ICU was expressed by 62% of the staff
      and 42% of the nurses. Tuberculosis-destroyed lung is a common indication for
      mechanical ventilation in acute exacerbation of chronic respiratory failure, and
      noninvasive ventilation was used in a limited number of ICUs.

PMID- 19119435
TI  - Normal ambulatory 24-hour esophageal pH values in Koreans -a multicenter study-.
AB  - Ambulatory 24-hr esophageal pH monitoring is considered the gold standard for
      diagnosing gastroesophageal reflux disease. The aim of this study was to
      establish normal values for gastroesophageal acid exposure in healthy Koreans.
      Fifty healthy volunteers (24 males and 26 females; mean age, 45 yr) without
      reflux symptoms and without reflux esophagitis or hiatal hernia on upper
      endoscopy underwent ambulatory 24-hr esophageal pH monitoring after esophageal
      manometry. The 95th percentiles for the reflux parameters were: the percent total
      time pH <4, 3.7%; the percent upright time pH <4, 5.7%; the percent supine time
      pH <4, 1.0%; the number of reflux episodes with pH <4, 76.5; the number of reflux
      episodes with pH <4 for >5 min, 1.5; the duration of the longest episode, 12.5
      min; and the composite score, 14.2. Age and gender were not associated with any
      of the pH parameters. In conclusion, physiological gastroesophageal reflux occurs
      in healthy Koreans. These normal esophageal pH values will provide reference data
      for clinical and research studies in Korea.

PMID- 19119436
TI  - Clinical and genetic analysis of Korean patients with facioscapulohumeral
      muscular dystrophy.
AB  - Facioscapulohumeral muscular dystrophy (FSHD) is an autosomal dominantly
      inherited muscular disorder, which is characterized by weakness of facial,
      shoulder and hip girdle, humeral, and anterior distal leg muscles. The FSHD gene
      has been mapped to 4q35 and a deletion of integral copies of a 3.3-kb DNA repeat
      motif named D4Z4 was known to be the genetic background of the disorder. Although
      FSHD is the second most common muscular dystrophy in adulthood, there were few
      reports on the genetically confirmed patients in Korea. Recently, we experienced
      four Korean patients with clinical features resembling FSHD. In order to confirm
      the diagnosis, conventional Southern blot (SB) analysis by using double digestion
      with EcoRI and BlnI and hybridization with p13E-11 probe was performed in three
      patients and newly developed long polymerase chain reaction (PCR) method was used
      for one patient because genomic DNA was not enough for conventional SB for this
      patient. All patients were demonstrated to have shortened D4Z4 repeats that were
      consistent with FSHD. Therefore, we could confirm the diagnosis of FSHD in four
      Korean patients and appropriate genetic counseling was done for the patients and
      their families. It is of note that long-PCR method could be a good alternative
      for conventional SB when D4Z4 repeats were less than 5.

PMID- 19119437
TI  - Evaluation of preterm delivery between 32-33 weeks of gestation.
AB  - Preterm labor after 34 weeks of gestation has shown no great difference from full
      term labor in terms of neonatal morbidity and mortality when proper antepartum
      management (antibiotics or steroids treatment) is done. However, various studies
      have discussed different views on the risks and safety of preterm delivery at
      32(+0)-33(+6) weeks of gestation. We evaluated the complications of different
      preterm groups that included the neonates born at 32(+0)-33(+6) weeks of
      gestation (142), stratified randomly selected neonates born at 34(+0)-36(+6)
      weeks of gestation (267) and neonates born after 37(+0) weeks of gestation (356)
      at our hospital between December 1999 and April 2006. As a result, it was found
      that neonates born at 34(+0)-36(+6) weeks of gestation showed no great difference
      from infants born at full term. However, neonates born at 32(+0)-33(+6) weeks
      were more likely to be admitted to neonatal intensive care unit or develop
      neonatal complications significantly than the neonates born at 34(+0)-36(+6)
      weeks and at full term. Therefore, it is suggested that neonates born at 32(+0)
      33(+6) weeks have higher risk of neonatal complications following their preterm
      labor than those born at later than 34(+0) weeks. Thus, it would be difficult to
      accept the idea that preterm labor at 32(+0)-33(+6) weeks is safe.

PMID- 19119438
TI  - Treatment-seeking behaviors and related epidemiological features in Korean acne
      patients.
AB  - Little is known about the treatment-seeking behaviors of acne patients,
      especially Asian acne patients. This study was performed to obtain detailed
      information about the treatment-seeking behaviors in Korean acne patients.
      Patients who visited the dermatology departments at 17 university hospitals
      completed a self-administered questionnaire. Most patients obtained information
      about acne from doctors or the Internet. The most important criteria for
      selecting a treatment method or choosing a particular clinic were effectiveness
      and accessibility. Patients used traditional medicine, visited beauty clinics,
      drank more water, and used over-the-counter topical agents more frequently than
      they sought doctors during the worsening period. The degree of satisfaction in
      treatment was found to depend on the total cost of treatment, number of places
      visited, site affected by acne, and emotional stress. Those who had experienced a
      side effect tended to have been treated for longer, to have paid more for
      treatment, and to have an associated skin disease. Treatments prescribed by
      dermatology clinics had the lowest aggravating rate, although improvement rates
      for family medicine clinics were also fairly high. This is the first study to
      investigate in detail the demographic features and characteristics of the
      treatment-seeking behaviors of acne patients in Asia.

PMID- 19119439
TI  - Trends in avoidable death over 20 years in Korea.
AB  - To evaluate the achievement of health care services in Korea independent of other
      socioeconomic factors, we observed the time trend of avoidable death between 1983
      and 2004. A list of avoidable causes of death was constructed based on the
      European Community Atlas of "Avoidable Death". We calculated sex- and age
      standardized mortality rates of Korean aged 1-64 yr using data of the Korea
      National Statistical Office. The avoidable mortality rate (per 100,000 persons)
      decreased from 225 to 84 in men and from 122 to 41 in women. Accordingly, the
      proportion of avoidable deaths among all classifiable deaths was reduced by 8.1%
      in men and 6.4% in women. However, mortality rates from some preventable causes
      such as ischemic heart disease and malignant neoplasms of lung, breast, cervix,
      and colorectum have been on the rise. Mortality preventable by appropriate
      medical care showed the greatest reduction (by 77.8%), while the mortality
      preventable by primary prevention showed the least reduction (by 50.0%). These
      findings suggest that health care service has significantly contributed to the
      improvement of health in Korea. However, more effective intervention programs
      would be needed given the less reduction in mortality avoidable by primary or
      secondary prevention than expected and unexpectedly increasing mortality from
      several preventable causes.

PMID- 19119440
TI  - Imipenem-resistant Pseudomonas aeruginosa: risk factors for nosocomial
      infections.
AB  - The aim of this study was to determine the risk factors for nosocomial infections
      of imipenem-resistant Pseudomonas aeruginosa (IRPA). A prospective case-control
      study was performed at a tertiary care hospital in Ankara from January to
      December 2004. The patients with nosocomial P. aeruginosa infection were included
      in the study. The features of the patients with IRPA infections were compared to
      those with imipenem-sensitive P. aeruginosa (ISPA) infections. Only the first
      isolation of P. aeruginosa was considered. Nosocomial infections were defined
      according to Center for Disease Control (CDC) criteria. IRPA was isolated from 75
      (44.1%) patients, and ISPA was isolated from 95 (55.9%) patients during the study
      period. IRPA were most frequently isolated from endotracheal aspirate (19%)
      cultures (p=0.048), whereas ISPA were most frequently isolated from urine (28%)
      cultures (p=0.023). In multivariate analysis, a longer duration of hospital stay
      until P. aeruginosa isolation (odds ratio [OR], 1.027; 95% confidence interval
      [CI], 1.002-1.054, p=0.034), arterial catheter administration (OR, 2.508; 95% CI,
      1.062-5.920, p=0.036), vancomycin (OR, 2.882; 95% CI, 1.130-7.349, p=0.027),
      piperacillin-tazobactam (OR, 6.425; 95% CI, 2.187-18.875, p=0.001), and imipenem
      (OR, 3.580; 95% CI, 1.252-10.245, p=0.017) treatment within the 14 days before
      isolation of IRPA were independently associated with imipenem resistance. It was
      concluded that treatment with imipenem, vancomycin and piperacillin-tazobactam
      were major risk factors for IRPA infections in hospitalized patients. The
      nosocomial occurrence of IRPA was also strongly related to the duration of
      hospital stay, arterial catheter administration.

PMID- 19119441
TI  - Etomidate should be used carefully for emergent endotracheal intubation in
      patients with septic shock.
AB  - Etomidate and midazolam are the most popular drugs among the induction agents for
      emergent endotracheal intubation. The purpose of this study was to compare the
      incidence of adrenal insufficiency and mortality between the septic shock
      patients who received etomidate (ETM group) and those who received midazolam (MDZ
      group). Between November 2004 and September 2006, 65 patients were analyzed in
      this study. The hospital mortality rate was 36% in the ETM group (n=25) and 50%
      in the MDZ group (n=40), which was not statistically significant (p=0.269). The
      incidence of relative adrenal insufficiency was significantly higher in the ETM
      group than in the MDZ group (84% and 48%, respectively; p=0.003). On multivariate
      analysis, the use of etomidate was the only significant factor affecting the
      incidence of relative adrenal insufficiency (odds radio, 5.59; 95% confidence
      interval, 1.61-19.4). In conclusion, we think that physicians who treat patients
      with septic shock should be aware that etomidate can cause adrenal insufficiency,
      and should start corticosteroids if etomidate is administered.

PMID- 19119442
TI  - Weekly low-dose docetaxel for salvage chemotherapy in pretreated elderly or poor
      performance status patients with non-small cell lung cancer.
AB  - Although docetaxel monotherapy has shown clinical benefits for previously treated
      patients with advanced non-small cell lung cancer (NSCLC), the efficacy of
      salvage docetaxel chemotherapy for elderly patients or patients with poor
      performance status (PS) is controversial. Therefore, we conducted a phase II
      trial to evaluate the safety and efficacy of weekly low-dose docetaxel
      monotherapy in these patients. Forty NSCLC patients, who had been previously
      treated with one or more chemotherapy regimens, received docetaxel at a dose of
      25 mg/m(2) weekly on days 1, 8, and 15 of a 28-day cycle. All patients were
      >or=65 yr or had a PS of grade 2 in the cases of <65 yr. Weekly low-dose
      docetaxel was well-tolerated. Grade 3/4 non-hematologic toxicities were rare;
      fatigue in 3 patients (8%), anorexia in 3 patients (8%) and stomatitis in 2
      patients (5%). Grade 3/4 neutropenia was noted in only one patient (3%). By
      intent-to-treat analysis, nine patients (23%) had partial responses and eleven
      patients (28%) demonstrated stable disease. The median progression-free survival
      and overall survival were 9.9 weeks and 37.7 weeks, respectively. Weekly low-dose
      docetaxel therapy provides a reasonable alternative for NSCLC salvage treatment
      in pretreated elderly patients or in patients with a reduced PS.

PMID- 19119443
TI  - Intra-operative measurement of surgical lengths of the rectum and the peritoneal
      reflection in Korean.
AB  - The lengths of the surgical rectum and peritoneal reflection were important
      factors in treatment modality of rectal tumor. To evaluate the surgical length of
      rectum, we measured the length of the peritoneal reflections, sacral promontory
      and termination of the taenia coli from the anal verge by rigid sigmoidoscope in
      23 male and 23 females during operation. The mean lengths of the sacral
      promontory were 16.5+/- 2.2 cm and 16.1+/-2.2 cm in the males and females,
      respectively. As for the peritoneal reflection, the results were anterior (8.8+/
      2.2 cm, 8.1+/-1.7 cm), lateral (10.8+/-2.7 cm, 11.4+/-1.9 cm) and posterior
      (13.8+/-2.5 cm, 14.0+/-1.9 cm), respectively. There were no statistically
      significant differences between male and female. And only height had a
      correlation with the length of sacral promontory both in male and female (p=0.015
      and p=0.018, respectively). For all the estimated lengths, the length of the
      sacral promontory had a correlation with the lengths of the anterior (p<0.001 and
      p=0.001) and posterior (p<0.001 and p<0.001) peritoneal reflections in males and
      females, respectively. We suggest that the intra-operative lengths of the rectum
      and peritoneal reflection will be useful information for treatment modality of
      rectal tumor clinically in Korean.

PMID- 19119444
TI  - Clinical relevance of pain patterns in osteoporotic vertebral compression
      fractures.
AB  - Few studies have been conducted to explain the pain patterns resulting from
      osteoporotic vertebral compression fractures (OVCF). We analyzed pain patterns to
      elucidate the pain mechanism and to provide initial guide for the management of
      OVCFs. Sixty-four patients underwent percutaneous vertebroplasty (N=55) or
      kyphoplasty (N=9). Three pain patterns were formulized to classify pains due to
      OVCFs: midline paravertebral (Type A), diffuse paravertebral (Type B), and remote
      lumbosacral pains (Type C). The degree of compression was measured using scale of
      deformity index, kyphosis rate, and kyphosis angle. Numerical rating scores were
      serially measured to determine the postoperative outcomes. As vertebral body
      height (VBH) decreased, paravertebral pain became more enlarged and extended
      anteriorly (p<0.05). Type A and B patterns significantly showed the reverse
      relationship with deformity index (p<0.05), yet Type C pattern was not affected
      by deformity index. Postoperative pain severity was significantly improved
      (p<0.05), and patients with a limited pain distribution showed a more favorable
      outcome (p<0.05). The improvement was closely related with the restoration of
      VBH, but not with kyphosis rate or angle. Thus, pain pattern study is useful not
      only as a guide in decision making for the management of patients with OVCF, but
      also in predicting the treatment outcome.

PMID- 19119445
TI  - Clinical comparison of distal pancreatectomy with or without splenectomy.
AB  - The spleen may be preserved during distal pancreatectomy (DP) for benign disease.
      The aim of this study was to compare the perioperative and postoperative courses
      of patients with conventional DP and spleen-preserving distal pancreatectomy
      (SPDP) for benign lesions or tumors with low-grade malignant potential occurred
      at the body or tail of the pancreas. A retrospective analysis was performed for
      the hospital records of all the patients undergoing DP and SPDP between January
      1995 and April 2006. One-hundred forty-three patients underwent DP and 37
      patients underwent SPDP. There were no significant differences in age, sex,
      indications of operation, estimated blood loss, operative time, and postoperative
      hospital stay between the two groups. Pancreatic fistula occurred in 21 (13.3%)
      patients following DP and in 3 (8.1%) following SPDP without a significant
      difference (p=0.081). Portal vein thrombosis occurred in 4 patients after DP.
      Splenic infarction occurred in one patient after SPDP. Overwhelming
      postosplenectomy infection was observed in one patient after DP. SPDP can be
      achieved with no increase in complication rate, operative time, or length of
      postoperative hospitalization as compared to conventional DP. Additionally, it
      has the advantage of reducing the risk of overwhelming postsplenectomy infection
      and postoperative venous thrombosis.

PMID- 19119446
TI  - The effect of different suturing techniques on astigmatism after penetrating
      keratoplasty.
AB  - The purpose of this study was to compare the effects on astigmatism after
      penetrating keratoplasty with three different suture techniques. In this
      prospective study, 38 eyes of 38 patients underwent penetrating keratoplasty with
      three suturing techniques: interrupted, single running, and double running.
      Topographic astigmatism was measured at 2, 6, 12, and 18 months after
      keratoplasty. During 18 months after surgery, the interrupted suture group had
      higher astigmatism than the double running suture group. There was no significant
      difference in the amounts of astigmatism during the first year after keratoplasty
      between the single running and the double running suture group. However, at 18
      months after surgery, when all sutures were out, the double running suture group
      (3.60+/-1.58 diopters) showed significantly less astigmatism than the single
      running group (5.65+/-1.61 diopters). In conclusion, post-keratoplasty
      astigmatism was the least in the double running suture group of the three
      suturing techniques at 18 months after penetrating keratoplasty.

PMID- 19119447
TI  - The significance of hemosiderin deposition in the lungs and organs of the
      mononucleated macrophage resorption system in infants and children.
AB  - Hemosiderin deposition is not often recognized on routine examination with
      hematoxylin and eosin staining; however, iron stains may be helpful in the
      evaluation of hemosiderin deposition in infant autopsies. This report describes
      the data obtained from autopsy of 86 infants and children whose deaths were
      investigated at the Forensic Medicine Council Bursa Morgue Department from
      January 2000 to January 2003. A histochemical technique was used to identify
      hemosiderin in lung, liver and spleen specimens, which was correlated with other
      descriptive variables such as the reported cause of death, postmortem interval,
      trauma history, gender, and age. There was a weakly positive but significant
      correlation between lung and liver hemosiderin scores (Spearman's rank
      correlation coefficient, rho=0.348, p=0.001); i.e., given an increase in lung
      hemosiderin scores, an increase in liver hemosiderin scores was also observed.
      Similarly, a marked positive correlation between spleen and liver hemosiderin
      scores (Spearman's rank correlation coefficient, rho=0.335, p=0.002) was
      observed. The probability of spleen hemosiderin-positive cases belonging to the
      age group under 6 months was found to be 4.3 times greater than those who were
      hemosiderin-negative (95% confidence interval, 1.6-11.8). After the major
      differential diagnoses were ruled out, this study demonstrated, that depending on
      the statistically assessed morphometric grounds, the presence of hemosiderin
      deposits in the liver and spleen were significantly higher in the age group under
      6 months.

PMID- 19119448
TI  - Different regulation of atrial ANP release through neuropeptide Y2 and Y4
      receptors.
AB  - Neuropeptide Y (NPY) receptors are present in cardiac membranes. However, its
      physiological roles in the heart are not clear. The aim of this study was to
      define the direct effects of pancreatic polypeptide (PP) on atrial dynamics and
      atrial natriuretic peptide (ANP) release in perfused beating atria. Pancreatic
      polypeptides, a NPY Y(4) receptor agonist, decreased atrial contractility but was
      not dose-dependent. The ANP release was stimulated by PP in a dose-dependent
      manner. GR 23118, a NPY Y(4) receptor agonist, also increased the ANP release and
      the potency was greater than PP. In contrast, peptide YY (3-36) (PYY), an NPY
      Y(2) receptor agonist, suppressed the release of ANP with positive inotropy. NPY,
      an agonist for Y(1, 2, 5) receptor, did not cause any significant changes. The
      pretreatment of NPY (18-36), an antagonist for NPY Y(3) receptor, markedly
      attenuated the stimulation of ANP release by PP but did not affect the
      suppression of ANP release by PYY. BIIE0246, an antagonist for NPY Y(2) receptor,
      attenuated the suppression of ANP release by PYY. The responsiveness of atrial
      contractility to PP or PYY was not affected by either of the antagonists. These
      results suggest that NPY Y(4) and Y(2) receptor differently regulate the release
      of atrial ANP.

PMID- 19119449
TI  - Additive antinociception between intrathecal sildenafil and morphine in the rat
      formalin test.
AB  - The possible characteristics of spinal interaction between sildenafil
      (phosphodiesterase 5 inhibitor) and morphine on formalin-induced nociception in
      rats was examined. Then the role of the opioid receptor in the effect of
      sildenafil was further investigated. Catheters were inserted into the intrathecal
      space of male Sprague-Dawley rats. For induction of pain, 50 microL of 5%
      formalin solution was applied to the hind-paw. Isobolographic analysis was used
      for the evaluation of drug interaction between sildenafil and morphine.
      Furthermore, naloxone was intrathecally given to verify the involvement of the
      opioid receptor in the antinociception of sildenafil. Both sildenafil and
      morphine produced an antinociceptive effect during phase 1 and phase 2 in the
      formalin test. The isobolographic analysis revealed an additive interaction after
      intrathecal delivery of the sildenafil-morphine mixture in both phases.
      Intrathecal naloxone reversed the antinociception of sildenafil in both phases.
      These results suggest that sildenafil, morphine, and the mixture of the two drugs
      are effective against acute pain and facilitated pain state at the spinal level.
      Thus, the spinal combination of sildenafil with morphine may be useful in the
      management of the same state. Furthermore, the opioid receptor is contributable
      to the antinocieptive mechanism of sildenafil at the spinal level.

PMID- 19119450
TI  - Expression of NAD(P)H oxidase subunits and their contribution to cardiovascular
      damage in aldosterone/salt-induced hypertensive rat.
AB  - NAD(P)H oxidase plays an important role in hypertension and its complication in
      aldosterone-salt rat. We questioned whether NAD(P)H oxidase subunit expression
      and activity are modulated by aldosterone and whether this is associated with
      target-organ damage. Rats were infused with aldosterone (0.75 microg/hr/day) for
      6 weeks and were given 0.9% NaCl+/-losartan (30 mg/kg/day), spironolactone (200
      mg/kg/day), and apocynin (1.5 mM/L). Aldosterone-salt hypertension was prevented
      completely by spironolactone and modestly by losartan and apocynin. Aldosterone
      increased aortic NAD(P)H oxidase activity by 34% and spironolactone and losartan
      inhibited the activity. Aortic expression of the subunits p47(phox), gp91(phox),
      and p22(phox) increased in aldosterone-infused rats by 5.5, 4.7, and 3.2-fold,
      respectively, which was decreased completely by spironolactone and partially by
      losartan and apocynin. Therefore, the increased expression of NAD(P)H oxidase may
      contribute to cardiovascular damage in aldosterone-salt hypertension through the
      increased expression of each subunit.

PMID- 19119451
TI  - Human cytomegalovirus IE1 protein enhances herpes simplex virus type 1-induced
      syncytial formation in U373MG cells.
AB  - Co-infection of herpes simplex virus type 1 (HSV-1) and human cytomegalovirus
      (HCMV) is not uncommon in immunocompromised hosts. Importantly, organ transplant
      recipients concurrently infected with HSV-1 and HCMV have a worse clinical
      outcome than recipients infected with a single virus. However, factors regulating
      the pathologic response in HSV-1, HCMV co-infected tissues are unclear. We
      investigated the potential biologic role of HCMV gene product immediate early 1
      (IE1) protein in HSV-1-induced syncytial formation in U373MG cells. We utilized a
      co-infection model by infecting HSV-1 to U373MG cells constitutively expressing
      HCMV IE1 protein, UMG1-2. Syncytial formation was assessed by enumerating nuclei
      number per syncytium and number of syncytia. HSV-1-induced syncytial formation
      was enhanced after 24 hr in UMG1-2 cells compared with U373MG controls. The
      amplified phenotype in UMG1-2 cells was effectively suppressed by roscovitine in
      addition to inhibitors of viral replication. This is the first study to provide
      histological evidence of the contribution of HCMV IE1 protein to enhanced
      cytopathogenic responses in active HSV-1 infection.

PMID- 19119452
TI  - Comparison of Her-2, EGFR and cyclin D1 in primary breast cancer and paired
      metastatic lymph nodes: an immunohistochemical and chromogenic in situ
      hybridization study.
AB  - The significant advance in the development of molecular-targeting drugs has made
      an evaluation of Her-2, EGFR, and cyclin D1 an important clinical issue in breast
      cancer patients. This study compared the Her-2, EGFR, and cyclin D1 status of
      primary tumors as well as their matching lymph node metastases using
      immunohistochemistry (IHC) and chromogenic in situ hybridization (CISH) in 73
      breast cancer patients. Her-2, EGFR, and cyclin D1 protein showed a concordance
      between the primary lesion and the metastatic regional lymph nodes in 82%, 90%,
      and 63%, respectively. CISH also revealed 92%, 93%, and 85% concordance in the
      gene amplification status of Her-2, EGFR, and cyclin D1, showing a reasonable
      agreement between primary tumors and metastatic regional lymph nodes. Although a
      statistically significant agreement was found in Her-2 expression, a relatively
      high discordance rate (18%) raises a little concern. Our findings suggest that
      the Her-2 status can be reliably assessed on primary tumor but a possible
      difference can be found in Her-2, EGFR, and cyclin D1 status between the primary
      and the metastatic sites and this possibility should be concerned in patients
      considering molecular targeted therapy or patients with progress of disease.

PMID- 19119453
TI  - Mitochondrial DNA aberrations of bone marrow cells from patients with aplastic
      anemia.
AB  - This study was undertaken primarily to test the hypothesis that mitochondrial DNA
      (mtDNA) mutations may be associated with aplastic anemia. Complete mtDNA
      nucleotide sequence was analyzed in nine and eight bone marrow specimens from
      Korean patients with aplastic anemia and healthy individuals, respectively. We
      found a large number of polymorphisms as well as apparent new mutations in both
      patients and controls throughout the entire mtDNA genome; 12 mutations harbored
      amino acid changes in patients and none of the mutations in controls produced
      amino acid changes. There were heteroplasmic mutations and more nonsynonymous
      mtDNA changes observed in patients, so the mean number of mtDNA aberrations of
      bone marrow cells showed statistically significant difference overall between
      patients (mean=25.6) and controls (mean=12.8) (p=0.019). Our data may support an
      association of mtDNA aberrations with aplastic anemia.

PMID- 19119454
TI  - Chromosomal losses are associated with hypomethylation of the gene-control
      regions in the stomach with a low number of active genes.
AB  - Transitional-CpG methylation between unmethylated promoters and nearby methylated
      retroelements plays a role in the establishment of tissue-specific transcription.
      This study examined whether chromosomal losses reducing the active genes in
      cancers can change transitional-CpG methylation and the transcription activity in
      a cancer-type-dependent manner. The transitional-CpG sites at the CpG-island
      margins of nine genes and the non-island-CpG sites round the transcription start
      sites of six genes lacking CpG islands were examined by methylation-specific
      polymerase chain reaction (PCR) analysis. The number of active genes in normal
      and cancerous tissues of the stomach, colon, breast, and nasopharynx were
      analyzed using the public data in silico. The CpG-island margins and non-island
      CpG sites tended to be hypermethylated and hypomethylated in all cancer types,
      respectively. The CpG-island margins were hypermethylated and a low number of
      genes were active in the normal stomach compared with other normal tissues. In
      gastric cancers, the CpG-island margins and non-island-CpG sites were
      hypomethylated in association with high-level chromosomal losses, and the number
      of active genes increased. Colon, breast, and nasopharyngeal cancers showed no
      significant association between the chromosomal losses and methylation changes.
      These findings suggest that chromosomal losses in gastric cancers are associated
      with the hypomethylation of the gene-control regions and the increased number of
      active genes.

PMID- 19119455
TI  - Biological profiles of Korean atomic bomb survivors in residence at Daegu and
      Kyungbuk, Republic of Korea.
AB  - In 1945, many Koreans, in addition to Japanese, were killed or injured by the
      atomic bombs dropped on Hiroshima and Nagasaki, Japan. This study compared the
      biological profiles of Korean atomic bomb survivors in residence at Daegu and
      Kyungbuk, Republic of Korea with those of a representative sample of Koreans
      obtained during a similar period. We evaluated anthropometric measurements, blood
      pressure, blood cell counts, blood chemistry, and urinalysis of survivors (n=414)
      and age- and sex-matched controls (n=414) recruited from the third Korea National
      Health and Nutrition Examination Survey conducted in 2005. Univariate analyses
      revealed significantly higher systolic blood pressure, white blood cell count,
      and serum total cholesterol, triglycerides, high-density lipoprotein-cholesterol,
      and aspartate aminotransferase levels (p<0.01) in the survivors. Conversely,
      hemoglobin concentration, hematocrit, red blood cell count, and the proportion of
      positive urine occult blood (p<0.01) were lower in the survivors. Our findings
      suggest that biological profiles of Korean atomic bomb survivors were adversely
      affected by radiation exposure.

PMID- 19119456
TI  - Fatal peripheral candidal suppurative thrombophlebitis in a postoperative
      patient.
AB  - We report a case of fatal fungal peripheral suppurative thrombophlebitis, caused
      by Candida albicans, which was disseminated to the blood, lungs, eyes, and spine.
      Clinical suspicion and aggressive management are important in managing fungal
      peripheral suppurative thrombophlebitis. Early clinical suspicion is important in
      managing fungal peripheral suppurative thrombophlebitis, and radical excision of
      the affected veins, recognition of metastatic foci, and use of systemic
      antifungal agents are essential to avoid septic shock and death.

PMID- 19119457
TI  - Partial trisomy 1q41 syndrome delineated by whole genomic array comparative
      genome hybridization.
AB  - Partial trisomy 1q syndrome is a rare chromosomal abnormality. We report on a
      male infant with 46,XY,der(11)t(1;11)(q41;p15.5) due to unbalanced segregation of
      the maternal reciprocal balanced translocation 46,XX,t(1;11)(q41;p15.5). The baby
      presented with a mild phenotype, characterized by a triangular face, almond
      shaped eyes, low ears, short stature with relatively long legs, and mild
      psychomotor retardation. We utilized whole genomic array comparative genome
      hybridization (CGH) with 4,000 selected bacterial artificial chromosomes (BACs)
      to define the chromosomal breakpoints and to delineate the extent of the partial
      trisomy in more detail. To our knowledge, this is the first case of nearly pure
      "partial trisomy 1q41" defined by whole genomic array CGH.

PMID- 19119458
TI  - Serial magnetic resonance imagings of multiple brain abscesses in a patient with
      pneumococcal meningoencephalitis.
AB  - We report a 43-yr-old man manifesting bacterial meningoencephalitis and multiple
      abscesses by Streptococcus pneumoniae. Serial magnetic resonance (MR) imagings
      and MR spectroscopy showed the evolution of multiple brain abscesses over 4
      weeks: the enhanced rings became thicker and the dimension of whole lesions
      larger despite shrinkage of the ring-enhanced regions. These findings may be
      evidence of active inflammation working to sequestrate the lesion and protect the
      surrounding normal brain parenchyma from additional damage, even in the final
      stage of the brain abscess.

PMID- 19119459
TI  - A novel mutation in the GATA1 gene associated with acute megakaryoblastic
      leukemia in a Korean Down syndrome patient.
AB  - Although acquired mutations in the GATA1 gene have been reported for Down
      syndrome-related acute megakaryoblastic leukemia (DS-AMKL) in Caucasians, this is
      the first report of a Korean Down syndrome patient with AMKL carrying a novel
      mutation of the GATA1 gene. A 3-yr-old Korean girl with Down syndrome was
      admitted to our hospital complaining of pallor and fever. The findings of a
      peripheral blood smear and bone marrow study were compatible with the presence of
      AMKL. A chromosome study showed 48,XX,-7,+21c,+21,+r[3]/47,XX,+21c[17]. Following
      GATA1 gene mutation analysis, a novel mutation, c.145dupG (p.Ala49GlyfsX18), was
      identified in the N-terminal activation domain of the GATA1 gene. This mutation
      caused a premature termination at codon 67 and expression of an abnormal GATA-1
      protein with a defective N-terminal activation domain, and the absence of full
      length GATA-1 protein. This case demonstrates that a leukemogenic mechanism for
      DS-AMKL is contributed by a unique collaboration between overexpressed genes from
      trisomy 21 and an acquired GATA1 mutation previously seen in Caucasians and now
      in a Korean patient.

PMID- 19119460
TI  - Foreign body inclusion cyst of the nasal radix after augmentation rhinoplasty.
AB  - Development of a cystic mass on the nasal dorsum is a very rare complication of
      aesthetic rhinoplasty. Most reported cases are of mucous cyst and entrapment of
      the nasal mucosa in the subcutaneous space due to traumatic surgical technique
      has been suggested as a presumptive pathogenesis. Here, we report a case of
      dorsal nasal cyst that had a different pathogenesis for cyst formation. A 58-yr
      old woman developed a large cystic mass on the nasal radix 30 yr after
      augmentation rhinoplasty with silicone material. The mass was removed via a
      direct open approach and the pathology findings revealed a foreign body inclusion
      cyst associated with silicone. Successful nasal reconstruction was performed with
      autologous cartilages. Discussion and a brief review of the literature will be
      focused on the pathophysiology of and treatment options for a postrhinoplasty
      dorsal cyst.

PMID- 19119461
TI  - Pituitary apoplexy producing internal carotid artery compression: a case report.
AB  - We report a case of pituitary apoplexy resulting in right internal carotid artery
      occlusion accompanied by hemiplegia and lethargy. A 43-yr-old man presented with
      a sudden onset of severe headache, visual disturbance and left hemiplegia.
      Investigations revealed a nodular mass, located in the sella and suprasellar
      portion and accompanied by compression of the optic chiasm. The mass compressed
      the bilateral cavernous sinuses, resulting in the obliteration of the cavernous
      portion of the right internal carotid artery. A border zone infarct in the right
      fronto-parietal region was found. Transsphenoidal tumor decompression following
      conservative therapy with fluid replacement and steroids was performed.
      Pathological examination revealed an almost completely infarcted pituitary
      adenoma. The patient's vision improved immediately after the decompression, and
      the motor weakness improved to grade IV(+) within six months after the operation.
      Pituitary apoplexy resulting in internal carotid artery occlusion is rare.
      However, clinicians should be aware of the possibility and the appropriate
      management of such an occurrence.

PMID- 19119462
TI  - Primary large cell neuroendocrine carcinoma of the breast: radiologic and
      pathologic findings.
AB  - Some breast neoplasms are classified as primary neuroendocrine carcinomas because
      they are positive for neuroendocrine markers. Although neuroendocrine carcinomas
      can originate from various organs of the body, primary neuroendocrine carcinomas
      of the breast are extremely rare. The diagnosis of primary neuroendocrine
      carcinoma of the breast can only be made if nonmammary sites are confidently
      excluded or if an in situ component can be found. Here we report a primary large
      cell neuroendocrine carcinoma (LCNL) involving the left breast. Breast
      ultrasonography revealed a lobulated, heterogeneous, low-echoic mass in the left
      breast, and the lesion appeared as a well-defined, highly-enhancing mass on a
      chest computed tomography scan. Ultrasound-guided core needle biopsy was
      performed on the mass, and primary LCNC was confirmed by histopathologic
      examination.

PMID- 19119463
TI  - Clear cell "sugar" tumor of the lung: a well-enhanced mass with an early washout
      pattern on dynamic contrast-enhanced computed tomography.
AB  - Clear cell tumor of the lung is a rare and very unusual benign pulmonary tumor.
      As clear cell tumor of the lung contains abundant cytoplasmic glycogen, this
      tumor is called "sugar tumor". We report a case of sugar tumor in a 64-yr-old man
      presenting as a round pulmonary nodule. On dynamic computed tomography (CT)
      scans, the solitary pulmonary nodule showed early wash-in enhancement with an
      early washout pattern like a lung malignancy. The patient underwent wedge
      resection for the tumor. Pathologic examination, including immunohistochemical
      studies, revealed that the nodule was a benign clear cell tumor, so-called "sugar
      tumor". Because only a small number of cases have been reported previously,
      clinical aspects, radiological characteristics on dynamic contrast-enhanced CT,
      and differential diagnosis of the tumor are not well established. Herein we
      present a clear cell tumor of the lung and discuss the clinical, radiological,
      and pathological features of the tumor.

PMID- 19119464
TI  - The jugular foramen schwannomas: review of the large surgical series.
AB  - OBJECTIVE: Jugular foramen schwannomas are uncommon pathological conditions. This
      article is constituted for screening these tumors in a wide perspective.
      MATERIALS: One-hundred-and-ninty-nine patients published in 19 articles between
      1984 to 2007 years was collected from Medline/Index Medicus. RESULTS: The series
      consist of 83 male and 98 female. The mean age of 199 operated patients was 40.4
      years. The lesion located on the right side in 32 patients and on the left side
      in 60 patients. The most common presenting clinical symptoms were hearing loss,
      tinnitus, disphagia, ataxia, and hoarseness. Complete tumor removal was achieved
      in 159 patients. In fourteen patients tumor reappeared unexpectedly. The tumor
      was thought to originate from the glossopharyngeal nerve in forty seven cases;
      vagal nerve in twenty six cases; and cranial accessory nerve in eleven cases. The
      most common postoperative complications were lower cranial nerve palsy and facial
      nerve palsy. Cerebrospinal fluid leakage, meningitis, aspiration pneumonia and
      mastoiditis were seen as other complications. CONCLUSION: This review shows that
      jugular foramen schwannomas still have prominently high morbidity and those
      complications caused by postoperative lower cranial nerve injury are life threat.

PMID- 19119465
TI  - The effect of premorbid demographic factors on the recovery of neurocognitive
      function in traumatic brain injury patients.
AB  - OBJECTIVE: Premorbid demographic backgrounds of injured individuals are likely to
      reflect more accurately the status of patients with traumatic brian injury (TBI)
      than clinical factors. However, the concrete study about the relationship between
      the demographic factors and neurocognitive function in TBI patients has not been
      reported. The object of this study was to evaluate the effect of premorbid
      demographic factors on the recovery of neurocognitive function following TBI.
      METHODS: From July 1998 to February 2007, 293 patients (male: 228, female: 65)
      with a history of head injury, who had recovered from the acute phase, were
      selected from our hospital to include in this study. We analyzed the effect of
      premorbid demographic factors including age, sex, educational level and
      occupation on the recovery of neurocognitive function in each TBI subgroup as
      defined by Glasgow Coma Scale (GCS) score. Intelligence and memory are components
      of neurocognitive function, and the Korean Wechsler Intelligence Scale (K-WAIS)
      and the Korean memory assessment scale (K-MAS) were used in this study. The
      results were considered significant at p<0.05. RESULTS: The higher level of
      education was a good prognostic factor for intelligence regardless of GCS score
      and younger age group showed a better result for memory with an exception of
      severe TBI group. In the severe TBI group, the meaningful effect of demographic
      factors was not noted by the cause of influence of severe brain injury.
      CONCLUSION: The demographic factors used in this study may be helpful for
      predicting the precise prognosis and developing an appropriate rehabilitation
      program for TBI patients.

PMID- 19119466
TI  - Posterior cervical fixation with nitinol shape memory loop in the anterior
      posterior combined approach for the patients with three column injury of the
      cervical spine : preliminary report.
AB  - OBJECTIVE: The authors reviewed clinical and radiological outcomes in patients
      with three column injury of the cervical spine who had undergone posterior
      cervical fixation using Nitinol shape memory alloy loop in the anterior-posterior
      combined approach. MATERIALS: Nine patients were surgically treated with anterior
      cervical fusion using an iliac bone graft and dynamic plate-screw system, and the
      posterior cervical fixation using Nitinol shape memory loop (Davydovtrade mark)
      at the same time. A retrospective review was performed. Clinical outcomes were
      assessed using the Frankel grading method. We reviewed the radiological
      parameters such as bony fusion rate, height of iliac bone graft strut, graft
      subsidence, cervical lordotic angle, and instrument related complication.
      RESULTS: Single-level fusion was performed in five patients, and two-level fusion
      in four. Solid bone fusion was presented in all cases after surgery. The mean
      height of graft strut was significantly decreased from 20.46+/-9.97 mm at
      immediate postoperative state to 18.87+/-8.60 mm at the final follow-up period
      (p<0.05). The mean cervical lordotic angle decreased from 13.83+/-11.84 degrees
      to 11.37+/-6.03 degrees at the immediate postoperative state but then, increased
      to 24.39+/-9.83 degrees at the final follow-up period (p<0.05). There were no
      instrument related complications. CONCLUSION: We suggest that the posterior
      cervical fixation using Nitinol shape memory alloy loop may be a simple and
      useful method, and be one of treatment options in anterior-posterior combined
      approach for the patients with the three column injury of the cervical spine.

PMID- 19119467
TI  - Prognostic value of serum s100 protein by elecsys s100 immunoassay in patients
      with spontaneous subarachnoid and intracerebral hemorrhages.
AB  - OBJECTIVE: The serum S100 protein has been known to reflect the severity of
      neuronal damage. The purpose of this study was to assess the prognostic value of
      the serum S100 protein by Elecsys S100 immunoassay in patients with subarachnoid
      hemorrhage (SAH) and intracerebral hemorrhage (ICH) and to establish reference
      value for this new method. METHODS: Serum S100 protein value was measured at
      admission, day 3 and 7 after bleeding in 42 consecutive patients (SAH : 20, ICH :
      22) and 74 healthy controls, prospectively. Admission Glasgow coma scale (GCS)
      score, Hunt & Hess grade and Fisher grade for SAH, presence of intraventricular
      hemorrhage, ICH volume, and outcome at discharge were evaluated. Degrees of serum
      S100 elevation and their effect on outcomes were compared between two groups.
      RESULTS: Median S100 levels in SAH and ICH groups were elevated at admission
      (0.092 versus 0.283 microg/L) and at day 3 (0.110 versus 0.099 microg/L) compared
      to healthy controls (0.05 microg/L; p<0001). At day 7, however, these levels were
      normalized in both groups. Time course of S100 level in SAH patient was
      relatively steady at least during the first 3 days, whereas in ICH patient it
      showed abrupt S100 surge on admission and then decreased rapidly during the next
      7 days, suggesting severe brain damage at the time of bleeding. In ICH patient,
      S100 level on admission correlated well with GCS score (r=-0.859; p=0.0001) and
      ICH volume (r=0.663; p=0.001). A baseline S100 level more than 0.199 microg/L
      predicted poor outcome with 92% sensitivity and 90% specificity. Logistic
      regression analyses showed Ln (S100) on admission as the only independent
      predictor of poor outcome (odd ratio 36.1; 95% CI, 1.98 to 656.3). CONCLUSION:
      Brain damage in ICH patient seems to develop immediately after bleeding, whereas
      in SAH patients it seems to be sustained for few days. Degree of brain damage is
      more severe in ICH compared to SAH group based on the S100 level. S100 level is
      considered an independent predictor of poor outcome in patient with spontaneous
      ICH, but not in SAH. Further study with large population is required to confirm
      this result.

PMID- 19119468
TI  - Multimodal treatment for complex intracranial aneurysms: clinical research.
AB  - OBJECTIVE: For patients with giant or dissecting aneurysm, multimodal treatment
      consisting extracranial-intracranial bypass surgery plus clip or coil for parent
      artery occlusion may be necessary. In this study, the safety and efficacy of
      multimodal treatment in 15 patients with complex aneurysms were evaluated
      retrospectively. METHODS: From January 1995 to June 2007, the authors treated 15
      complex aneurysms that were unable to be clipped or coiled. Among them, nine
      patitents had unruptured aneurysms and 6 had ruptured aneurysms. Aneurysms were
      located in the internal cerebral artery (ICA) in 11 patients (4 in the dorsal
      wall, 4 in the terminal ICA, 1 in the paraclinoid, and 2 in the cavernous ICA),
      in the middle cerebral artery (MCA) in 2, and in the posterior circulation in two
      patients RESULTS: Fifteen patients with complex aneurysms were treated with
      bypass surgery previously. Thirteen patients were treated with external carotid
      middle cerebral artery (ECA-MCA) anastomosis, and one patient with superficial
      temporal to posterior cerebral artery (STA-PCA) and another patient with
      occipital artery to posterior inferior cerebellar artery (OA-PICA) anastomosis.
      Parent artery occlusion was then performed with a clip in 9 patients, with a coil
      in 4, with balloon plus coil in one patient. All 15 aneurysms were successfully
      treated with clip or coil combined with bypass surgery. Follow-up angiograms
      showed good patency of anastomotic site in 10 out of 11 patients, and perfusion
      study showed sufficient perfusion in 6 out of 9 patients. CONCLUSION: These
      findings indicate that for patients with complex aneurysms, clip or coil for
      parent vessel occlusion with additive bypass surgery can successfully exclude the
      aneurysm from the neurovascular circulatory system.

PMID- 19119469
TI  - Contralateral reherniation after open lumbar microdiscectomy : a comparison with
      ipsilateral reherniation.
AB  - OBJECTIVE: To evaluate the risk factors that may be responsible for the
      development of contralateral reherniations from ipsilateral ones after open
      lumbar microdiscectomy (OLM), and to compare surgical outcomes of revision OLM
      for contralateral reherniations with those for ipsilateral ones. METHODS:
      Seventeen patients who underwent revision OLM for contralateral reherniation were
      enrolled into Group I, and 35 patients who underwent revision OLM for ipsilateral
      reherniation were enrolled into Group II. Using medical charts and imaging study
      results, the differences in the clinical and radiological factors were evaluated
      between the two groups. Clinical outcomes of each group were compared between the
      two groups. RESULTS: Significant differences were found in the interval to
      reherniation from initial surgery (33 months for Group I and 18.6 months for
      Group II, p=0.009), as well as in the incidences of both protruded disc (35.3%
      for Group I and 8.6% for Group II, p=0.045) and mild disc degeneration (29.4% for
      Group I and 5.7% for Group II, p=0.031) at initial surgery. On binary multi
      logistic regression analysis, significant differences were found in the interval
      to reherniation (p=0.027, Odds ratio=1.051) and incidence of mild disc
      degeneration (p=0.025, Odds ratio=12.03) between the two groups. There were no
      significant differences in the improvement of clinical outcomes after revision
      OLM between the two groups. CONCLUSION: The interval to reherniation from initial
      surgery and the grade of disc degeneration at initial surgery were key factors
      that distinguished the development of contralateral reherniations from
      ipsilateral ones. Surgical outcomes of revision OLM were similar in both groups.

PMID- 19119470
TI  - Rabbit Model for in vivo Study of Intervertebral Disc Degeneration and
      Regeneration.
AB  - OBJECTIVE: The purpose of this study is to verify the usefulness of the rabbit
      model for disc degeneration study. MATERIALS: The L1-L2, L2-L3, L3-L4, or L4-L5
      lumbar intervertebral disc (IVD) of 9 mature male New Zealand White rabbits were
      injured by inserting a 16-gauge needle to a depth of 5 mm in the left
      anterolateral annulus fibrosus while leaving L5-L6 IVD uninjured. Three other
      rabbits also received intradiscal injections of rabbit disc cells transfected
      with adenovirus and bone morphogenetic protein-2 (ad-BMP-2) at L4-L5 in addition
      to injury by 16-gauge needle at the L1-L2 level. Using digitized radiographs,
      measurements of IVD height were made and analyzed by using the disc height index
      (DHI). Magnetic resonance imaging (MRI) scans of the injured discs, injected
      discs, and uninjured L5-L6 discs were performed at 15 weeks post surgery and
      compared with preoperative MRI scans. RESULTS: All twelve rabbits showed
      consistent results of disc degeneration within 15 weeks following annular
      puncture. DHIs of injured discs were significantly lower than that of the
      uninjured L5-L6 discs (p<0.05). The mean value of disc degeneration grade of
      injured discs was significantly higher than that of uninjured discs (p<0.05). The
      injection of disc cell transfected with ad-BMP-2 did not induce disc regeneration
      at 15 weeks after injection. CONCLUSION: This study showed that the injured disc
      had a significant change in DHI on simple lateral radiograph and disc
      degeneration grade on MRI scans within 15 weeks in all rabbits. Rabbit annular
      puncture model can be useful as a disc degeneration model in vivo.

PMID- 19119471
TI  - Spinal intradural extramedullary mature cystic teratoma in an adult.
AB  - Spinal intradural extramedullary teratoma is a rare condition that develops more
      commonly in children than in adults and may be associated with spinal dysraphism.
      We report a rare case of adult-onset intradural extramedullary teratoma in the
      thoracolumbar spinal cord with no evidence of spinal dysraphism and without the
      history of prior spinal surgery. The patient was a 38-year-old male whose chief
      complaint was urinary incontinence. X-ray images of the thoracolumbar spine
      showed the widening of the interpedicular distance and posterior marginal erosion
      of the vertebral bodies and pedicles at the T11, T12, and L1 level. Magnetic
      resonance imagings of the lumbar spine showed a lobulated inhomogeneous high
      signal intradural mass (87x29x20 mm) between T11 and L1 and a high signal fluid
      collection at the T11 level. Laminectomy of the T11-L1 region was performed, and
      the mass was subtotally excised. The resected tumor was histopathologically
      diagnosed as a mature cystic teratoma. The patient's symptom of urinary
      incontinence was improved following the surgery.

PMID- 19119472
TI  - Three-dimensional angiographic demonstration of plexiform fenestrations of the
      proximal anterior cerebral artery associated with a ruptured aneurysm.
AB  - A rare case of ruptured aneurysm associated with multiple A(1) fenestrations
      resembling plexiform network was demonstrated by 3D angiography. A 56-year-old
      female presented with a ruptured aneurysm in the A(2) segment of the left distal
      anterior cerebral artery associated with the right A(1) fenestration. The
      ruptured aneurysm was occluded with surgical neck clipping via interhemispheric
      approach without neurological deficit. Plexiform fenestrations of the right
      distal A(1), opposite side to the left ruptured A(2) aneurysm, were clearly
      visible on postoperative 3D angiography. Our case may strongly support the theory
      described by Paget, namely that a remnant of the plexiform anastomosis between
      the primitive olfactory artery and A(1) segment is the source of such
      fenestration.

PMID- 19119473
TI  - Disseminated intravascular coagulation in a patient undergoing removal of
      metastatic brain tumor.
AB  - The authors present a case of 68-year-old woman who underwent resection of a
      metastatic adenocarcinoma in the left parietooccipital area. The intraoperative
      course was uneventful; however, after closure of the scalp incision, increased
      bleeding from the suture line was noted. A computerized tomography scan that was
      performed immediately after operation revealed acute epidural hemorrhage with
      mass effect under the bone flap. The patient developed disseminated intravascular
      coagulation and immediate re-exploration was performed. This patient was
      successfully treated owing to early recognition of the condition and immediate
      treatment with transfusion. Neurosurgeons should be alert that hypercoagulabe
      state is common in cancer patients and consumptive coagulopathy can occur after
      resection of metastatic brain tumor.

PMID- 19119474
TI  - Intraventricular cavernous malformation radiologically mimicking meningioma.
AB  - We report a case of trigonal cavernous malformation (CM) radiologically mimicking
      meningioma. The computed tomographic (CT) head angiography and magnetic resonance
      imaging (MRI) showed a partially calcified lesion with slight contrast
      enhancement located in the area of the left atrium of lateral ventricle. The
      lesion was completely removed using microsurgery with a parieto-occipital
      transcortical approach. The resected mass was histologically confirmed as CM. CM
      should be considered as differential diagnosis in case of the atrial mass lesion
      due to lack of hemosiderin ring characteristically seen other seated CM.

PMID- 19119475
TI  - Clinical and serological characterization of autoimmune hemolytic anemia in a
      tertiary care hospital in North India.
AB  - Clinical and serological characterization of autoimmune hemolytic anemia (AIHA)
      helps in the diagnosis, management, and monitoring course of disease. In the
      present study, we serologically characterized the red-cell-bound autoantibodies
      in diagnosed AIHA patients with regards to antibody class, subclass, direct
      antiglobulin test (DAT) strength, and their correlation with in vivo hemolysis. A
      total of 157 samples were evaluated for DAT. Clinically and serologically, 43 of
      them were diagnosed as AIHA. Detailed serological characterization of
      autoantibodies was performed in these 43 patients using the gel technology.
      Hematological and biochemical parameters were obtained from the Hospital
      Information System. Polyspecific (immunoglobulin G (IgG) + C3) DAT-positive
      samples were tested for monospecific DAT (IgG, IgM, IgA, C3c, and C3d) and IgG
      subclass (IgG1 and IgG3). Thermal amplitude of autoantibodies was determined on
      eluates. Median age of the patients was 31 years (range, 12-70 years) with male
      to female ratio of 1:3.3. In 55.8% of patients, AIHA was secondary to an
      underlying disorder. Patients with strong reactive DAT had increased likelihood
      of hemolysis (p = 0.000). IgG was the solitary autoantibody coating the red cells
      in 72.1% of patients. Red cells coated with multiple immunoglobulins/complements
      and IgG subclass IgG1 and/or IgG3 were more susceptible to undergo hemolysis. Gel
      technology helps the immunohematologist to diagnose and serologically
      characterize AIHA patient with regard to red-cell-bound autoantibodies' class,
      subclass, and titer as these correlate with in vivo hemolysis.

PMID- 19119476
TI  - Renal crystal storing histiocytosis in a patient with multiple myeloma.

PMID- 19119477
TI  - The potential of cytokeratin 20 and mucin 2 mRNA as metastasis markers in
      regional lymph nodes of colon cancer patients investigated by quantitative RT
      PCR.
AB  - PURPOSE: The presence of regional lymph node metastases is one of the most
      important prognostic factors in colon cancer. Nevertheless, up to 30% of the
      lymph node negative patients experience disease recurrence. Possibly, this
      patient group may be identified by more sensitive techniques than routine
      histopathological examination of the lymph nodes. METHODS: In the present study,
      we have evaluated the detection of colon cancer lymph node metastases by real
      time RT-PCR quantitation of the epithelial-specific cytokeratin 20 (CK20) and
      mucin 2 (MUC2) mRNAs. RESULTS: Both assays were able to detect dilutions of tumor
      cells down to one tumor cell in 10(6) normal lymphocytes. CK20 and MUC2 mRNA were
      quantitated in 52 normal lymph nodes from 12 patients undergoing surgery for
      benign bowel diseases and in 144 primary colon tumors. The median tumor level of
      both markers were more than 10(4)-fold higher than the highest level in normal
      lymph nodes, indicating that the markers had a potential for metastasis detection
      in a clinical context. We applied the assays to 61 lymph nodes with known
      metastases detected by routine staining. Elevated CK20 or MUC2 mRNA levels were
      detected in 57 (95%) of the 61 LNs. CONCLUSIONS: Thus, CK20 and MUC2 quantitation
      by real-time RT-PCR seems to be a promising, sensitive tool to detect metastases
      in regional lymph nodes from colon cancer patients.

PMID- 19119478
TI  - Surgical management of Mirizzi syndrome.
AB  - BACKGROUND/AIMS: Mirizzi syndrome is an unusual presentation of prolonged
      cholelithiasis. This study aimed to analyze the diagnostic methods, operative
      strategies, and outcome of the surgical treatment of patients with Mirizzi
      syndrome. METHODS: We retrospectively evaluated the patients with Mirizzi
      syndrome treated in our General Surgery Clinic. The data collected included
      demographic variables, clinical presentation, diagnostic methods, surgical
      procedures, and postoperative complications. RESULTS: The study included 13 male
      and 21 female patients, with a mean age of 67.2 years. The incidence of Mirizzi
      syndrome was determined as 0.6% (34/5632), and type II was more frequently
      observed (52.9%); no patient was determined as type IV. The incidences of types I
      and III were 35.2% and 11.7%, respectively. Among the preoperative diagnostic
      evaluations, ultrasonography was the initial imaging study that was performed in
      all patients. Computerized tomography, magnetic resonance
      cholangiopancreatography, and endoscopic retrograde cholangiopancreatography were
      the other radiological studies. Surgical procedures included cholecystectomy for
      83% of the patients with type I. The remaining cases and 14 of the type II
      patients (77.7%) underwent choledochotomy and T-tube insertion following
      cholecystectomy. Four of the patients with type II variety and all of the type
      III patients underwent cholecystectomy and roux-en-Y hepaticojejunostomy. All of
      the patients had complete recovery, with a morbidity rate of 5.8%, and there was
      no hospital mortality. CONCLUSIONS: The essential part of the management of
      patients with Mirizzi syndrome is to determine the best surgical procedure in the
      preoperative period. In type I patients, simple cholecystectomy is generally
      enough, but sometimes T-tube insertion may be required, while the cases with
      types II-IV require more complex surgical approach, such as cholecystectomy and
      bilioenteric anastomosis. Roux-en-Y hepaticojejunostomy is an appropriate
      procedure with good outcome.

PMID- 19119479
TI  - Chronic hepatitis B. A guideline to diagnosis, approach, management, and follow
      up 2007. Turkish Association for the Study of Liver.

PMID- 19119480
TI  - Hepatocellular carcinoma pathogenesis: does PPAR alpha polymorphism have a role
      in hepatocarcinogenesis associated with HBV and HCV infections?

PMID- 19119481
TI  - Bone mineralization in children with inflammatory bowel disease: what is the role
      of zinc?
AB  - BACKGROUND/AIMS: Bone demineralization is a significant problem in pediatric
      inflammatory bowel disease. Contributing factors include inadequate nutrition,
      corticosteroid therapy and decreased physical activity. Although zinc is needed
      for osteoblastic activity and collagen synthesis, its role in bone development is
      uncertain. The aim of this study was to investigate the relation between the
      serum zinc level and bone mineral indexes of 28 children with inflammatory bowel
      disease. METHODS: Bone mineral content and bone mineral density at lumbar 1-4
      vertebrae were measured by dual energy X-ray absorptiometry in all patients and
      56 controls. Serum zinc levels of patients and 31 controls were determined by
      spectrophotometric method. RESULTS: The mean bone mineral density values of
      patients and controls were 0.661+/-0.201 g/cm2 and 0.751+/-0.175 g/cm2, the mean
      bone mineral content values were 33.357+/-17.104 g and 38.968+/-14.663 g, and the
      mean serum zinc levels were 101.2+/-28.8 microg/dl and 108.9+/-15.9 microg/dl,
      respectively. All controls had normal serum zinc level; however, 11 (39.3%)
      patients had low serum zinc level (p=0.000). The ratio of patients with Z-score
      below the -2SD was higher in patients with low zinc level than in patients with
      normal zinc level (70% vs. 42.8%). CONCLUSIONS: Although insignificant, some of
      the children with IBD had low levels of serum zinc and these patients had lower Z
      scores than the others. Further studies including large numbers of patients may
      reveal a certain effect of zinc on bone development in patients with inflammatory
      bowel disease.

PMID- 19119482
TI  - Does the severity of tissue eosinophilia of colonic neoplasms reflect their
      malignancy potential?
AB  - BACKGROUND/AIMS: It was speculated that there was a relationship between the
      intensity of tissue eosinophilic infiltration in colonic malignancies and their
      prognosis. This retrospective study aimed to investigate the frequency and
      intensity of tissue eosinophilia in various colonic neoplasms, including serrated
      adenomas. METHODS: We evaluated 448 colonic neoplasms to determine eosinophilic
      infiltration: 96 hyperplastic polyps, 50 serrated adenomas, 19 flat adenomas, 154
      tubular adenomas, 71 tubulovillous adenomas, 13 villous adenomas and 45
      adenocarcinomas. The eosinophilic infiltration was categorized into three groups
      by evaluating the percentage of eosinophils relative to total stromal
      inflammatory cells: mild (0-5%), moderate (5-40%), and marked (>;40%). Chi-square
      and Fisher's exact tests were used for analyses. P value <0.05 was considered
      statistically significant. RESULTS: Moderate (46.7%) and marked (52.9%) intensity
      were noted in all colonic adenomas. Most of the hyperplastic polyps (96%) and
      adenocarcinomas (75.6%) showed mild intensity. Mostly moderate eosinophilic
      infiltration was observed in serrated adenomas. CONCLUSIONS: Our findings suggest
      that the intensity of tissue eosinophilia is most prominent in adenomas including
      serrated adenomas and is diminished from adenoma to carcinoma. This finding may
      be used as a diagnostic indicator.

PMID- 19119483
TI  - PPAR-alpha L162V polymorphism in human hepatocellular carcinoma.
AB  - BACKGROUND/AIMS: Several lines of evidence suggest that peroxisome proliferator
      activated receptor alpha may be involved in hepatocarcinogenesis. L162V
      polymorphism of the peroxisome proliferator-activated receptor alpha gene
      enhances the transactivation activity of this transcription factor. The aim of
      this study was to determine the frequency and clinical correlates of peroxisome
      proliferator-activated receptor alpha L162V polymorphism in hepatitis virus
      induced hepatocellular carcinoma. METHODS: 90 hepatocellular carcinoma patients
      diagnosed at Ankara University Gastroenterology Clinic between January 2002 and
      July 2003 and 80 healthy controls with normal body mass index, blood chemistry
      and with negative viral serology were included. peroxisome proliferator-activated
      receptor alpha L162V polymorphism was determined by PCR-RFLP. RESULTS:
      hepatocellular carcinoma etiologies were as follows: 56 HBV, 12 HBV+HDV, 22 HCV.
      Eighty-seven patients (97%) were cirrhotic, and 60 patients (67.5%) had advanced
      tumors. In 83 (92%) of 90 hepatocellular carcinoma patients, gene segment
      including polymorphic region could be amplified by PCR (50 HBV, 12 HBV+HDV, 21
      HCV) and 6 of them (7.2%, all infected with HBV) had L162V polymorphism, while 2
      (2.5%) of 80 controls had this polymorphism (p=0.162). This trend became more
      remarkable when only HBV (HBV+HDV)-infected patients were compared with controls
      (6/62, 9.7% vs. 2/80, 2.5%, respectively, p=0.071). Five of 6 patients with L162V
      had advanced disease. CONCLUSIONS: Peroxisome proliferator-activated receptor
      alpha L162V polymorphism tends to occur in HBV-induced hepatocellular carcinoma
      and is absent in HCV-related hepatocellular carcinoma. These findings may show
      clues for the existence of different carcinogenesis mechanisms in these two
      common etiologies. Frequent occurrence of advanced disease in patients with L162V
      polymorphism suggests a role for this polymorphism in tumor progression.

PMID- 19119485
TI  - The relationship between chronic HCV infection and the level of plasma
      adiponectin.
AB  - BACKGROUND/AIMS: Metabolic products (TNFalpha, adiponectin, resistin, etc.),
      which are effective in insulin sensitivity and in the regulation of inflammation,
      play an important role in the development of metabolic disorders and fatty liver
      disease. The aim of this study was to evaluate the effect of HCV infection alone
      on plasma adiponectin levels and insulin sensitivity when metabolic factors are
      minimized and to determine whether chronic HCV infection causes hepatosteatosis
      through its effect on these factors. METHODS: This study was carried out between
      2006-2007, at the Gastroenterology Clinic of Izmir Ataturk Training and Research
      Hospital, in 30 non-diabetic patients with chronic HCV infection and 30 healthy
      subjects as controls. BMI (<26 kg/m2), fasting plasma glucose level, and
      ultrasonography were normal in both groups. In the patient group, HCV RNA was >
      or =1.90 x 10(3) IU/ml, ALT and AST were two times normal, and histological
      fibrosis scores were 1-2 in liver biopsy. Serum adiponectin levels and HOMA-IR
      were compared. RESULTS: Fasting blood glucose levels, body mass index and HOMA-IR
      of the two groups were similar and normal. The mean ALT value was significantly
      higher in the patient group [61.8 U/L vs 28.17 U/L (p<0.05)]. The mean viral load
      was determined as 5.6 x 10(5) IU/ml in the chronic HCV patient group. The mean
      plasma adiponectin concentrations were 71.07 microg/ml in chronic HCV patients
      and 82.07 microg/ml in the control group, and the difference was statistically
      insignificant (p>0.05). CONCLUSIONS: In the absence of metabolic disorders such
      as obesity, diabetes mellitus and hepatosteatosis, chronic HCV infection does not
      affect insulin sensitivity or adiponectin concentration.

PMID- 19119484
TI  - The ACE gene I/D polymorphism does not affect the susceptibility to or prognosis
      of PBC.
AB  - BACKGROUND/AIMS: Primary biliary cirrhosis is an autoimmune liver disease that is
      strongly influenced by poorly defined, complex genetic factors. Alterations of
      the renin-angiotensin system have been implicated in the pathogenesis of various
      diseases. A deletion polymorphism of a 287-bp fragment of intron 16 of the
      angiotensin converting enzyme gene allele results in higher levels of circulating
      enzyme. Angiotensin converting enzyme deletion genotype has been linked to
      hypertension and sarcoidosis and has been reported to regulate liver fibrosis in
      HCV-mediated liver disease. We investigated the frequency of the Angiotensin
      converting enzyme gene insertion/deletion polymorphism in primary biliary
      cirrhosis patients. METHODS: 52 biopsy-proven primary biliary cirrhosis patients
      and 98 healthy controls were evaluated. Angiotensin converting enzyme
      insertion/deletion polymorphism was detected by polymerase chain reaction
      amplification of a genomic DNA fragment on intron 16 of the angiotensin
      converting enzyme gene. Clinical phenotype of primary biliary cirrhosis was
      verified with positive anti-mitochondrial antibody or M2 antibody, demonstration
      of cholestatic liver enzymes, and staging of liver biopsy. The differences
      between these variables among different genotypes were noted. RESULTS: There was
      no significant difference in genotypes and allele frequency between the primary
      biliary cirrhosis group and controls. The D allele frequency was 54% in primary
      biliary cirrhosis cases and 55% in controls (p=ns). Furthermore, there was no
      significant difference in clinical features between patients with angiotensin
      converting enzyme-insertion or insertion/deletion genotypes vs. patients with
      angiotensin converting enzyme-deletion genotype. CONCLUSIONS: In our limited
      sample, the angiotensin converting enzyme deletion genotype did not make a
      significant contribution to the pathogenesis or progression of primary biliary
      cirrhosis.

PMID- 19119486
TI  - Multifocal intestinal stromal tumors with jejunal perforation and intra-abdominal
      abscess: report of a case.
AB  - A 70-year-old man with right-sided abdominal pain, inappetence, nausea, and
      bloating of one-week duration was admitted to our Emergency Department. The
      abdominal computed tomographic scan showed an abscess (55 x 66 mm) among the
      intestinal loops. After percutaneous ultrasonography-guided insertion of a
      drainage catheter into the abscess, pouchography showed that contrast medium had
      passed into the intestinal lumen via fine tract. The patient underwent surgery
      because of an intraabdominal abscess caused by intestinal perforation. During
      laparotomy, a solid mass measuring 5 cm in diameter on the antimesenteric side of
      the jejunal wall and a perforation of approximately 0.5 cm were identified after
      exploration of the abscess cavity. In addition, 3 polypoid lesions (2 at the
      antimesenteric side of the jejunal wall, and 1 at the antimesenteric side of the
      ileal wall) were found incidentally. Resection and primary anastomosis of the
      perforated area and wedge resections of the polypoid lesions were performed. The
      results of pathologic examination of the all-surgical specimens indicated low
      grade gastrointestinal stromal tumors. Since there was no metastasis, all the
      tumors were resected surgically and all were pathologically low-grade tumors, we
      did not use imatinib, the long-term results of which are not known at present.
      Neither complications nor evidence of recurrence were seen during the follow- up
      of 13 months. Stromal tumors of the small intestine are relatively rare and cause
      subtle clinical signs and symptoms. Their diagnosis is often delayed until
      complications develop. Even if complications occur, exact diagnosis is usually
      very difficult preoperatively.

PMID- 19119487
TI  - A case of diffuse nodular lymphoid hyperplasia.
AB  - Diffuse nodular lymphoid hyperplasia represents a rare disease that is grossly
      characterized by the presence of numerous visible mucosal nodules measuring up
      to, and rarely exceeding, 0.5 cm in diameter. These may involve the entire small
      intestine, the large intestine, or both. The etiology is unknown. When diffuse
      nodular lymphoid hyperplasia is found predominantly in the colon, it can mimic a
      variety of polyposis syndromes and this may cause difficulties in diagnosis. The
      disease may be associated with other pathologies, especially gastrointestinal
      malignancies. This causes controversy when deciding the treatment options.
      Following patients without any treatment may lead to malignant progression, while
      surgical treatment may result in unnecessary radical resections because of
      obscurity in the diagnosis. We report here a diffuse nodular lymphoid hyperplasia
      case who underwent a radical resection because of obscurity in the diagnosis.

PMID- 19119488
TI  - Rapidly growing giant solitary cavernous hemangioma in a patient with ulcerative
      colitis.
AB  - Cavernous hemangiomas are rare lesions of the colon that usually present with
      painless, recurrent bleeding. Hemangiomas can be capillary or cavernous type, and
      80% of rectal hemangiomas are cavernous type. Ulcerative colitis is an
      inflammatory disorder that affects the rectum and, occasionally, the whole colon.
      Diarrhea, rectal bleeding and mucous discharge characterize ulcerative colitis.
      We present a 61-year-old man with painless rectal bleeding due to a solitary
      cavernous hemangioma of the rectum. He had been diagnosed with distal type
      ulcerative colitis in 2003. He was asymptomatic under mesalazine treatment until
      May 2005, when he presented with new onset bright red rectal bleeding and mucous
      discharge, despite still defecating normal stools once a day. Rectosigmoidoscopic
      examination revealed mucosal hyperemia, edema, granularity, and a hyperemic,
      friable mass lesion 5x4 cm in diameter in the rectum. Following excision,
      histopathologic examination of the mass was consistent with cavernous hemangioma.
      There was a six-month period between the rectosigmoidoscopy in which the
      cavernous hemangioma (5x4 cm in diameter) was detected and the former
      rectosigmoidoscopy with no reported hemangioma. Thus, this was considered a
      rapidly growing cavernous hemangioma. Intralesional microhemorrhages may cause
      rapid enlargement of the hemangiomas. Ulcerative colitis is characterized by
      inflammation, which may interfere with vascular integrity and augment
      intralesional microhemorrhage. We postulate that the inflammatory background of
      ulcerative colitis may have accelerated intralesional hemorrhage and growth of
      this coincidental rectal cavernous hemangioma. To the best of our knowledge, this
      is the only case of this sort in the literature.

PMID- 19119489
TI  - POEMS syndrome: a case report.
AB  - A 43-year-old female patient admitted with a 2.5-year history of lower extremity
      symmetrical sensorimotor polyneuropathy, hypertrichosis, sweating, diarrhea,
      weight loss, and hyperpigmentation. The clinical evaluation met the criteria for
      the diagnosis of POEMS syndrome. The patient was initially treated with
      prednisolone and responded well. We planned high-dose chemotherapy with
      autologous stem cell rescue and introduced a more immunosuppressive regimen
      containing cyclophosphamide and dexamethasone. We present a case differing from
      the other cases with her 2 g/day proteinuria and hypertrophic osteoarthropathy.

PMID- 19119490
TI  - Adenovirus infection as possible cause of acute liver failure in a healthy child:
      a case report.
AB  - Adenoviruses are common viral pathogens in childhood; however, they can cause
      serious disease in an immunocompromised host. Fulminant hepatitis is a rare
      complication of adenoviral infection. We report herein a case of fatal fulminant
      hepatitis possibly caused by adenovirus infection. Although rare, adenovirus
      infection should be considered in the differential diagnosis of acute liver
      failure in immunocompetent children.

PMID- 19119491
TI  - Duodenal variceal bleeding successfully treated with transjugular intrahepatic
      portosystemic shunt: a case report and review of the literature.
AB  - Duodenal varices are uncommon causes of gastrointestinal bleeding. In the
      literature, treatment of duodenal variceal bleeding is limited to case reports
      and case series. Treatment options are endoscopic, interventional radiologic and
      surgical modalities. In this article, we presented a case of a successful
      duodenal variceal bleeding treatment with transjugular intrahepatic portosystemic
      shunt. The other treatment modalities are also reviewed.

PMID- 19119492
TI  - Jejunal lipoma causing intussusception and gastrointestinal bleeding.

PMID- 19119493
TI  - An atypical initial presentation of Crohn's disease.

PMID- 19119494
TI  - Rectosigmoid endometriosis.

PMID- 19119495
TI  - Ansa pancreatica: a rare pancreas ductal variation.

PMID- 19119496
TI  - Carcinoid tumor of the ampulla of Vater presenting as recurrent acute acalculous
      cholecystitis attacks.

PMID- 19119497
TI  - Current awareness in human psychopharmacology.

PMID- 19119498
TI  - NZNO should support GST off food.

PMID- 19119499
TI  - Pondering the RN badge.

PMID- 19119500
TI  - Support sought for rural nurse survey.

PMID- 19119501
TI  - A tribute to a fabulous nurse and mentor.

PMID- 19119502
TI  - Can the preoperative Ca-125 level predict optimal cytoreduction in patients with
      advanced ovarian carcinoma? A single institution cohort study.
AB  - BACKGROUND: Preoperative Ca-125 level has been used as a predictor of optimal
      cytoreduction in advanced ovarian carcinoma. Yet, controversy exists regarding
      the ability of the tumor marker to predict optimal debulking and moreover of the
      proper cut-off limit to do so. METHODS: The preoperative Ca-125 levels of 426
      patients with Stage III/IV ovarian carcinoma from a single institution were
      correlated with surgical outcome. Optimal was considered the cytoreduction if the
      largest residual tumor was < or equal to 1 cm in diameter. Receiver operation
      characteristic (ROC) curve data were combined with interval likelihood ratios at
      various Ca-125 levels to determine the cut-off level with the maximum prognostic
      power. Sensitivity, specificity, positive and negative predictive values and
      accuracy were also calculated. RESULTS: Preoperative Ca-125 proved to be a
      reliable predictor for optimal cytoreduction. The area under curve of the ROC
      curve was 0.89, 98% C.I.=[0.828-0.952], indicating very good discriminating
      capability. The level of 500 IU/ml was found to have the most predictive power.
      The sensitivity of Ca-125 at that level was 78.5%, the specificity 89.6%, the
      positive predictive value 84.2%, the negative predictive value 85.4% and its
      accuracy 85%. Furthermore, the likelihood ratio for correct discrimination
      between optimal and sub-optimal cytoreduction, dropped sharply from 6.33, 95%
      C.I. [5.19-10.91] at the level of 500 IU/ml to 0.58, 95% C.I. [0.21-1.63] at the
      level of 600 IU/ml. CONCLUSIONS: Our data indicate that preoperative Ca-125 is a
      good predictor for optimal cytoreduction. the best threshold for this prediction
      proved to be 500 IU/ml. These patients may be candidates for neo-adjuvant
      chemotherapy treatment. Nevertheless, all clinical and radiological findings must
      be co-evaluated.

PMID- 19119503
TI  - Preventing sexually transmitted infections, 2008.

PMID- 19119504
TI  - AIDS treatment should start sooner.

PMID- 19119505
TI  - More women choose mastectomy.  Newer screening methods can detect breast cancer
      early, so mastectomy may be unnecessary.  So, why is it on the rise?

PMID- 19119506
TI  - New osteoporosis guidelines for men.  Six out of every 100 men will have the
      disease by age 65; earlier preventive steps are recommended.

PMID- 19119507
TI  - [Medicine and medical care].

PMID- 19119508
TI  - [From vulnerability model to resilience model].

PMID- 19119509
TI  - Update on human infections caused by intestinal protozoa.
AB  - PURPOSE OF REVIEW: To update the reader on the recent literature discussing human
      infections due to intestinal protozoa. RECENT FINDINGS: Diarrheal diseases due to
      intestinal protozoa cause significant morbidity and mortality worldwide in a
      variety of patient populations. New literature on key pathogens Cryptosporidium,
      Cyclospora, Isospora, Giardia, and Entamoeba histolytica are discussed. SUMMARY:
      The recent medical literature on these pathogens has focused on new advances in
      understanding human genetic markers associated with susceptibility to infection
      and the use of molecular diagnostic techniques for both outbreak investigations
      (molecular epidemiology) and to understand the variability of clinical disease
      within species and subspecies.

PMID- 19119510
TI  - Endoscopic treatment of colonic obstruction.
AB  - PURPOSE OF REVIEW: Over the past 15 years, great strides have been made in the
      nonsurgical management of malignant large bowel obstruction. Progress continues,
      particularly in the area of self-expanding metal stents. The purpose of this
      review is to assess the available endoscopic techniques for colonic decompression
      and document the inexorable trend toward supremacy of the self-expanding metal
      stent in this arena. RECENT FINDINGS: Stents are being designed with the
      structure and function of the colon in mind allowing better and longer-lasting
      palliation. Improvement in the design of the colonic decompression tube allows a
      low-tech approach to the palliation of colonic obstruction. Argon plasma
      coagulation is helpful in restoring continuity of the obstructed colonic lumen in
      certain circumstances. SUMMARY: As a consequence of technological innovation and
      growing expertise in the community, gastroenterology is becoming the go to
      specialty in the early management and palliation of malignant bowel obstruction.

PMID- 19119511
TI  - Dermatologic manifestations of colonic disorders.
AB  - PURPOSE OF REVIEW: The skin is often a mirror for matters of internal diseases
      including disorders of the gastrointestinal tract. Here we enumerate many
      cutaneous and gastrointestinal associations and focus closely on three of the
      lesser known cutaneous manifestations of colonic disorders. RECENT FINDINGS: Muir
      Torre syndrome involves cutaneous sebaceous adenomas and internal malignancy;
      screening of cutaneous lesions for microsatellite instability, and absence of
      mismatch repair genes provides an opportunity for diagnosis of the syndrome.
      Degos' disease is a vasoocclusive disorder involving the cutaneous and
      gastrointestinal systems; this disease affects all ages with significant
      mortality, yet a benign variant only affecting the skin is described. Anecdotally
      reported treatments are listed. Metastatic Crohn's disease is the development of
      noncaseating granulomas at skin sites not contiguous with the gastrointestinal
      tract; cutaneous lesions may precede the onset of colonic disease or appear in
      the absence of active bowel disease, and extensive surgical debridement of
      perineal lesions is often necessary. SUMMARY: Knowledge of these cutaneous
      manifestations provides an insight into the state of colonic health. These clues
      alert the clinician to the potential for life-threatening consequences, which
      leads to vigilant screening and hopefully earlier diagnosis.

PMID- 19119512
TI  - [Application of rifabutin, a rifamycin-group antibiotic, to patients with
      tuberculosis].

PMID- 19119513
TI  - [The frontline of clinical mycobacteriology].

PMID- 19119514
TI  - [Trends in the concept of resilience in psychiatry].

PMID- 19119515
TI  - [Resilience in schizophrenia].

PMID- 19119516
TI  - [Doing gender in sport: discourses on femininity and gymnastics in the FRG and
      the GDR].

PMID- 19119517
TI  - Military and naval hospitals in Malta in the last two centuries.

PMID- 19119518
TI  - [Resilience in mental disorders--special reference to biological research].

PMID- 19119519
TI  - FEM: a window onto the cultural coalescence of a Mexican feminist politics of
      sexuality.

PMID- 19119520
TI  - [From general systems theory to fuzzy theory, or: Dr. Jekyll and Mr. Hyde in
      science and technology].

PMID- 19119521
TI  - [The T complex of the mouse: a failure rich with instruction].

PMID- 19119522
TI  - The abnormal flight: the migration and repatriation of Irish unmarried mothers.

PMID- 19119523
TI  - "Dear Dolly's" advice: representations of youth, courtship, and sexualities in
      Africa, 1960-1980.

PMID- 19119524
TI  - [Concept of resilience in the French speaking world].

PMID- 19119525
TI  - [Significance of ICD-11 in diagnosis of schizophrenia].

PMID- 19119526
TI  - [Usefulness of and difficulties in ICD-10 for diagnosis of mood disorders--its
      diagnostic guidelines and standards].

PMID- 19119527
TI  - [Problems in ICD-10 and future tasks in ICD-11: F4 neurotic disorders, stress
      related disorders, and somatization disorders].

PMID- 19119528
TI  - [Statistical views of reality and problems in diagnosis of personality disorders
      in the Matsuzawa Hospital in Tokyo].

PMID- 19119529
TI  - [For treatment of diseases involving the inner ear: the frontier of basic
      research].

PMID- 19119530
TI  - [Perilymphatic fistula].

PMID- 19119531
TI  - [Basis of economics of clinical medicine (15)].

PMID- 19119532
TI  - [Health of parents and children and school health (7): "Pediatric chronic
      diseases and special education].

PMID- 19119533
TI  - [Exercise-physical activity and public health (7): Maintenance and improvement of
      physical strength].

PMID- 19119534
TI  - [Current status and future problems of tuberculosis control in Japan (1): History
      of tuberculosis control policies in Japan].

PMID- 19119536
TI  - Managed care considerations: hematologic cancer as a chronic disease.

PMID- 19119535
TI  - [Regional health of the 21st century (1): the dawn of the new public health].

PMID- 19119537
TI  - HBeAg/anti-HBe, alanine aminotransferase and HBV DNA levels in HBsAg positive
      chronic carriers.
AB  - Serum samples from a total of 72 chronic hepatitis B virus carriers were analysed
      by serological, biochemical and molecular assays. The aim was to evaluate the
      relationship of the serological and biochemical parameters with molecular markers
      in order to assess the infectivity of virus. Out of 72 chronic HBsAg positive
      carriers, 28 patients were HBeAg positive and anti-HBe negative, 38 patients were
      HBeAg negative and anti-HBe positive, only 3 patients were positive for both
      HBeAg and anti-HBe and the rest 3 patients were negative for both markers.
      Detectable HBV DNA lcvcl was found in 92.86% HBsAg-positive/anti-HBe negative
      patients along with raised alanine aminotransferase (ALT) level (67.86%) compared
      with HBeAg-negative/anti-HBe positive carriers (36.84%) (p value = 0.02) and out
      a total of 38 HBeAg-negative/anti-HBe positive carriers, 12 (31.58%) patients had
      detectable lcvel of HBV DNA. Among the 14 HBeAg-negative/anti-HBe positive
      patients with elevated ALT level, 8 (57.14%) had detectable HBV DNA whereas out
      of 24 HBeAg-negative/anti-HBe positive patients with normal ALT level only 4
      (16.66%) had detectablc HBV DNA lcvel. Significantly high rate of detection of
      HBV DNA was seen among anti-HBe positive patients with raised ALT level compared
      with the patients with normal ALT level (p value = 0.01).

PMID- 19119538
TI  - Magnetic resonance imaging features of breasts in patients with nipple discharge.
AB  - A retrospective study was conducted to demonstrate the potential role of dynamic
      contrast enhanced magnetic resonance imaging (DCEMRI) in the detection of breast
      lesions in 15 patients with nipple discharge. The DCEMRI findings were compared
      and correlated with the findings of ultrasonography and mammography. The results
      revealed that the character of the nipple discharge was mostly bloody and in few
      cases were serous. The imaging findings revealed that DCEMRI is highly sensitive
      and specific in the detection of breast canner and the histopathological
      correlation in such detection was highly significant (p < 0.001) as compared to
      ultrasonography and mammography finding.

PMID- 19119539
TI  - Clinicopathological correlation of blistering diseases of skin.
AB  - Blistering diseases are alarming skin conditions where blister formation occurs
      in various ways and cannot be differentiated clinically. For confirmation of
      diagnosis, along with routine histological examination, immunofluorescence study
      is essential. Tzanck smear may be used as a rapid diagnostic tool. We included
      here 34 cases of different blistering lesions. Other than routine Hematoxylin and
      Eosin stain, direct immunofluorescence test was done in 31 cases, indirect
      immunofluorescence in 28 cases and Tzanck smear in 33 cases. Direct
      immunofluorescence stain was also applied on Tzanck smears. The most frequent
      diagnoses were pemphigus (n = 16), bullous pemphigoid (n = 11) and linear IgA
      dermatosis (n = 3). Clinical findings and histological examination were
      sufficient for the diagnosis of most cases. Direct immunofluorescence study is
      essential in many cases, and indirect immunofluorescence study is a useful method
      for diagnosis of some of the blistering diseases, especially in pemphigus. Direct
      immunofluorescence staining on Tzanck smear is a novel technique for the
      diagnosis of pemphigus.

PMID- 19119540
TI  - Bangladesh HIV/AIDS communication challenges and strategies.
AB  - Bangladesh is in a precarious position in relation to the HIV/AIDS epidemic.
      Rates are currently low compared to the rest of the South Asian region, and the
      disease is relatively confined to small, high-risk populations--mainly injection
      drug users (IDUs) and commercial sex workers. Yet if steps are not taken quickly
      to keep the epidemic in check, it could easily spread to the general population
      as it has in other countries nearby. This would both increase the negative impact
      of HIV/AIDS and make it much harder to target for containment. It is therefore
      imperative that healthy behavior be promoted among IDUs and sex users, not only
      for their own health, but for the health of the country. Prevention will be the
      key to halting the spread of HIV infection through the implementation of
      communication and education programs aimed to change high-risk behavior. However,
      the disparate number of HIV/AIDS prevention programs independently operating in
      Bangladesh combined with the difficulty in adequately targeting this unique
      population of IDUs and sex workers establishes a complex situation where
      attaining behavior change is extremely difficult. This paper proposes adoption of
      the FOMENT model to design a health communication campaign targeting the high
      risk populations in Bangladesh.

PMID- 19119541
TI  - Phase contrast microscopic examination of hematuria to localize the source of
      bleeding.

PMID- 19119542
TI  - Use of anthropometric indicators for predicting risk of delivering low birth
      weight babies.

PMID- 19119543
TI  - Outcome of 153 cases of mitral stenosis after percutenuous transvenous mitral
      commissurotomy.

PMID- 19119544
TI  - Prevalence of overweight and obesity in infancy.

PMID- 19119545
TI  - Surface electromyography of the masticatory muscles for application in dental
      practice. Current evidence and future developments.
AB  - On the basis of well-founded clinical evaluations and taking into account special
      methodological recommendations, surface electromyography (EMG) enables the
      acquisition of valid and reliable quantitative data on the functional condition
      of the masticatory muscles as a "neuromuscular functional analysis". On the basis
      of a current review of the literature, surface EMG appears to be able to deliver
      additional diagnostic and therapy-relevant information. Meaningful EMG data can
      be gained regarding resting activity, maximum muscle activation, frequency
      spectrum under various loading conditions, as well as bilateral symmetry of the
      contraction behavior of the jaw muscles. With these parameters--completed by
      kinematic information on movements of the mandible--it appears to be possible
      under clinical conditions to assess (a) the neuromuscular chewing performance
      after prosthetic reconstructions, (b) to record the influence of pain on the
      neuromuscular system, and (c) to document the individual efffect of therapeutic
      interventions on temporomandibular disorders.

PMID- 19119546
TI  - Effect of digital noise filters on diagnostic radiographs for the diagnosis of
      experimental root fractures.
AB  - This article discusses basic concepts of noise suppression for digital
      radiographs, and shows how false application of algorithms available can lead to
      a loss of information. Noise suppression realized with low pass convolution
      filters are designed to decrease strong grey level changes of neighboring pixels.
      Sixty-two extracted fully intact premolars were selected and treated usingthe
      crown-down technique to prepare them for experimental fractures. A total of 358
      radiographs were taken, of which 312 images were selected with clearly visible
      root fractures. The selected radiographs were stored as uncompressed images and
      manipulated with 8 different convolution filters. A total of 2496 raw and
      filtered images were inspected for visible root fractures. Only the arithmetic
      mean filter with 5 x 5 kernel size led to a deletion of the visible fracture line
      in 33.3% of the inspected cases. The other filters proved to be useful for noise
      reduction without loss of any necessary diagnostic information. None of the
      filters improved the diagnostic outcome in the 46 remaining radiographs which did
      not show clearly visible root fractures before application of the filters.

PMID- 19119547
TI  - Telescopically retained removable partial dentures on CAD/CAM generated all
      ceramic primary telescopes.
AB  - The provision of patients with removable partial dentures on all-ceramic primary
      crowns with electroplated gold secondary parts is described as an alternative
      worthy of consideration in dental journals, lectures and in further training
      courses. The mode of operation is based on a precise, frictionless, passive fit
      between female and male components. To guarantee this even over large spans,
      intraoral joining of the individual components is necessary. However, this
      requires a different sequence of the treatment steps. The different procedures
      (conventional, procedure by Weigl, modified concept) are described in the
      following article. Clinical considerations, design principles, and special
      characteristics involved in producing the partial denture are explained.

PMID- 19119548
TI  - Cantilevered restorations using CAD/CAM Cerec chairside technology: a case
      report.
AB  - This paper describes a special case in which Cerec 3 chair-side could
      successfully replace a congenitally missing lateral incisor using a cantilever
      approach. The patient was in her mid-thirties and well motivated towards the full
      ceramic treatment. The waxed-up model along with the software yielded a creative
      Cerec-produced cantilever bridge across tooth 12 and attached to tooth 13.
      Surprisingly, the veneer on the canine could support a cantilever (on the lateral
      incisor) with very good performance to date (over 1 year).

PMID- 19119549
TI  - Cancer screening in older patients: life expectancy, prioritization, and health
      literacy.

PMID- 19119550
TI  - Prostate cancer screening: let patients decide.

PMID- 19119552
TI  - Screening for chlamydial infection.

PMID- 19119551
TI  - Colorectal cancer screening works--if we do it.

PMID- 19119553
TI  - Sidelined by cancer.

PMID- 19119554
TI  - Assessing breast cancer risk in women.
AB  - Understanding modifiable and nonmodifiable factors that increase or decrease
      breast cancer risk allows family physicians to counsel women appropriately.
      Nonmodifiable factors associated with increased breast cancer risk include
      advanced age, female sex, family history of breast cancer, increased breast
      density, genetic predisposition, menarche before age 12 years, and natural
      menopause after age 45 years. Hormonal factors associated with breast cancer
      include advanced age at first pregnancy, exposure to diethylstilbestrol, and
      hormone therapy. Environmental factors include therapeutic radiation. Obesity is
      also associated with increased rates of breast cancer. Factors associated with
      decreased cancer rates include pregnancy at an early age, late menarche, early
      menopause, high parity, and use of some medications, such as selective estrogen
      receptor modulators and, possibly, nonsteroidal anti-inflammatory agents and
      aspirin. No convincing evidence supports the use of dietary interventions for the
      prevention of breast cancer, with the exception of limiting alcohol intake.

PMID- 19119555
TI  - Cancer screening in the older patient.
AB  - Although there are clear guidelines that advise at what age to begin screening
      for various cancers, there is less guidance concerning when it may be appropriate
      to stop screening. The decision to stop screening must take into account
      patients' age; overall health and life expectancy; the natural history of the
      disease; and the risks, expense, and convenience of the screening test, and any
      subsequent testing and treatment. The U.S. Preventive Services Task Force and the
      American Academy of Family Physicians suggest that Papanicolaou smears can be
      discontinued in women at 65 years of age, provided they have had adequate recent
      normal screenings. Evidence suggests that cessation of breast cancer screening at
      approximately 75 to 80 years of age is appropriate, although American Geriatric
      Society guidelines recommend cessation at a more advanced age. Studies support
      continuing colon cancer screening until approximately 75 years of age in men and
      80 years of age in women for patients without significant comorbidities. Prostate
      cancer screening, if conducted at all, may be discontinued at approximately 75
      years of age in otherwise healthy men. Ultimately, the decision to screen or to
      discontinue screening must be made after careful discussion with each patient,
      using evidence-based guidelines and individual patient preferences.

PMID- 19119556
TI  - Information from your family doctor: screening for cancer.

PMID- 19119557
TI  - Prostate cancer screening: the continuing controversy.
AB  - Prostate cancer is the second most common cancer in men, with a lifetime
      prevalence of 17 percent. Prostate cancer symptoms generally occur in advanced
      stages, making early detection desirable. Digital rectal examination and prostate
      specific antigen testing are the most commonly used screening tools. The goal of
      screening is to detect clinically significant prostate cancers at a stage when
      intervention reduces morbidity and mortality; however, the merits and methods of
      screening continue to be debated. Prostate-specific antigen levels may be less
      than 4 ng per mL in 15 to 38 percent of men with cancer, indicating a high false
      negative rate. The positive predictive value of the prostate-specific antigen
      test is approximately 30 percent; therefore, less than one in three men with an
      abnormal finding will have cancer on biopsy. These limitations of the prostate
      specific antigen test have led to variations designed to improve its accuracy
      (e.g., age- and race-specific cutoffs, free prostate-specific antigen tests);
      however, none of these modifications have been widely adopted because of unclear
      benefits. Although treatments have improved in the past two decades, therapy for
      prostate cancer is not benign and may lead to urinary incontinence, sexual
      dysfunction, or bowel dysfunction. New evidence affecting screening
      recommendations continues to accumulate, and two large randomized controlled
      trials of screening will be completed in the next few years. Current guidelines
      recommend an individualized, targeted, patient-centered discussion to facilitate
      a shared decision about screening plans.

PMID- 19119558
TI  - Colorectal cancer: a summary of the evidence for screening and prevention.
AB  - Colorectal cancer causes significant morbidity and mortality in the United
      States. The incidence of colorectal cancer can be reduced with increasing efforts
      directed at mass screening of average-risk adults 50 years and older. Currently,
      fecal occult blood test and flexible sigmoidoscopy have the highest levels of
      evidence to support their use for colorectal cancer screening. Colonoscopy does
      not have a proven colorectal cancer mortality benefit, but it does have the
      greatest single-test accuracy, and it is the final test in the pathway to
      evaluate and treat patients with other abnormal screening tests. Double-contrast
      barium enema has sparse data of effectiveness. Computed tomographic colonography,
      fecal DNA testing, and Pillcam Colon are promising tests that need further study
      before they can be recommended for widespread screening. Routine screening should
      continue until 75 years of age. There is good evidence that fiber and
      antioxidants are not effective for primary prevention of colorectal cancer; they
      should not be recommended for chemoprevention. There is good evidence that
      aspirin, nonsteroidal antiinflammatory drugs, and cyclooxygenase-2 inhibitors are
      effective for decreasing the risk of colorectal cancer and adenomatous polyps,
      but increased risks, such as gastrointestinal bleeding, limit their usefulness.
      There is fair evidence that obesity is associated with colorectal cancer.
      Additional studies are needed on decreased fat intake and red meat consumption,
      and the use of calcium, vitamin D, and statins before these can be recommended
      for primary prevention of colorectal cancer.

PMID- 19119559
TI  - Information from your family doctor: colon cancer screening.

PMID- 19119560
TI  - Sharps injuries: a blunt assessment.

PMID- 19119561
TI  - A justice, of sorts.

PMID- 19119562
TI  - Promoting health.

PMID- 19119563
TI  - Targeting early discharge.

PMID- 19119564
TI  - A place in the sun.

PMID- 19119565
TI  - The heart of the matter.

PMID- 19119566
TI  - Brief advice for 'harmful' drinkers.

PMID- 19119567
TI  - Keeping in touch.

PMID- 19119568
TI  - Accidental digital injection of adrenaline.
AB  - Nurses working in emergency care often have to manage patients with
      undifferentiated and previously undiagnosed conditions. This month, Emergency
      Nurse continues to look at how emergency nurses across the UK have tackled them.

PMID- 19119569
TI  - Catastrophic haemorrhage and emergency care.

PMID- 19119570
TI  - Board's eye view.

PMID- 19119571
TI  - Oral health-related quality of life and its associated factors in an Indian adult
      population.
AB  - PURPOSE: The objectives of this study were to describe oral health-related
      quality of life (OHRQoL) and its associated factors in an Indian adult
      population. MATERIALS AND METHODS: Four hundred and fourteen general dental
      patients completed the Indian translations of the oral health impact profile
      (OHIP)-14 and the general health questionnaire (GHQ)-12 through personal
      interviews. A clinical examination was also performed for dental caries,
      gingivitis and plaque levels. RESULTS: Sufficient reliability (infinity = 0.85)
      and construct validity were demonstrated for the questionnaire. The mean decayed,
      missing or filled teeth of the study population was 6.93 and the mean gingival
      index and plaque index scores were 1.07 and 1.06, respectively. Caries status and
      the number of missing teeth were found to be significantly correlated with most
      of the subdomains of the OHIP-14. The GHQ-12 scores were also significantly
      correlated with the 'functional limitation' and 'psychological disability'
      domains of the OHIP-14. Higher OHIP-14 scores were associated with higher dental
      anxiety. Females perceived a higher sense of 'social handicap' and 'handicap' due
      to their oral status than males. It was also found that patients with caries and
      missing teeth had higher GHQ-12 scores. CONCLUSIONS: The results of this study
      showed that caries status, psychological distress and dental anxiety had an
      important effect on the OHRQoL.

PMID- 19119572
TI  - Oral habits in the primary and mixed dentitions of some Nigerian children: a
      longitudinal study.
AB  - PURPOSE: To longitudinally evaluate oral habits and their effects on the
      developing occlusion in Nigerian children. MATERIALS AND METHODS: A longitudinal
      epidemiological survey of 145 3- to 5-year-old children in a pre-primary section
      of a primary school near the Dental Centre, University College Hospital, Ibadan,
      Nigeria. The children at the first examination (Time 1) were screened for oral
      habits. They were then followed up and those located 4 years later were
      reassessed for oral habits (Time 2) in the primary school section of the same
      establishment. Only subjects who were actively engaged in non-nutritive sucking
      were coded positive. The occlusal features at Time 1 were recorded according to
      Foster and Hamilton, whereas at Time 2 the molar relationship was based on
      Angle's classification. Both descriptive statistics and Pearson correlation
      coefficient were used in the data analysis. RESULTS: At Time 1, only 5 (3.4%)
      children in the original sample size were non-nutritive suckers, whereas at Time
      2, 19 (31%) of the final sample size were involved in oral habits, with three of
      the initial children still involved, giving an incidence rate of 26.2%. Of the
      initial five non-nutritive suckers at Time 1, four were digit suckers and one a
      lip sucker. At Time 2, eight children were involved in digit sucking; seven in
      tongue thrusting/sucking, two in both digit and tongue sucking and two were nail
      biters. Five (4.5%) of 11 subjects with a Class 1 molar relationship at Time 1
      had a Class II molar relationship at Time 2. The correlations between the oral
      habits at the two stages of occlusal development and anterior open bite were
      statistically significant (P < 0.01). CONCLUSIONS: There was an increase in the
      number of children involved in oral habits at the early mixed dentition stage
      with significant correlations between oral habits and anterior open bite as well
      as a higher tendency towards Class II molar relationship for those with initial
      Class I.

PMID- 19119573
TI  - Measuring oral health-related quality-of-life using OHQoL-GE in periodontal
      patients presenting at the University of Berne, Switzerland.
AB  - PURPOSE: To assess the impact of oral health related quality-of-life (OHQoL) on
      patients presenting at the Department of Periodontology and Fixed Prosthodontics
      using a German version (the OHQoL-GE) of the oral health-related quality-of-life
      in the UK (OHQoL-UK) questionnaire. MATERIALS AND METHODS: A total of 251
      patients were invited to fill out the OHQoL-GE. In addition, patients were given
      a checklist of dental-related items over the past year including 'tooth ache',
      'dental treatment', 'bleeding gums', 'swollen gums' and 'problems with dental
      prosthesis'. Prior to being seen by a dental professional, the patients completed
      the questionnaires. During the new patient clinic visit, medical and dental
      history, age, gender, number of teeth present and presence or absence and type of
      dental prosthesis were recorded. In addition, a basic periodontal examination
      (BPE) was performed. RESULTS: Two hundred and fifteen OHQoL-GE questionnaires
      were completed. OHQoL-GE scores were significantly associated with patients' self
      reported symptoms and problems in the past year: experiences of 'tooth ache' (P <
      0.05), 'swollen gums' (P < 0.001) and 'problems with dental prosthesis' (P <
      0.05) with the exception of 'bleeding gums' (P = 0.102) and 'dental treatment' (P
      = 0.739). In addition, OHQoL-GE scores were directly correlated with the BPE
      (r(s) = -0.295, P < 0.01), the number of teeth present (r(s) = 0.190, P < 0.01)
      and inversely correlated with age (r(s) = 0.152, P < 0.05). Patients with
      removable partial dentures had the lowest median score of 43 (interquartile
      range, IQR 23), patients without dental prosthesis had a median score of 46 (IQR
      18) and patients with fixed dental prosthesis (FDP) had the highest score of 54
      (IQR 26). The differences were statistically significant between patients without
      dentures and patients with FDP (P < 0.05), and between removable denture wearers
      and patients with FDP (P < 0.05). CONCLUSIONS: The issues were periodontal and
      prosthetic status, number of teeth present and age impact on quality-of-life.
      This has implications in understanding the consequences of dental health and in
      the use of patient-centred outcomes in dental research. The OHQoL-GE demonstrates
      discriminative validity in a population seeking dental advice and/or treatment.

PMID- 19119574
TI  - Risk indicators for tooth loss due to caries and periodontal disease in
      recipients of free dental treatment in an adult population in Bangladesh.
AB  - PURPOSE: The aims of this study were first to identify the risk indicators for
      permanent tooth extraction in patients who were receiving free dental treatment,
      and second to determine whether or not the reasons for tooth extraction are
      related to socio-demographic factors. MATERIALS AND METHODS: Bangladeshi adults
      who visited Dhaka Dental College Hospital participated in this study. For each
      extraction, the clinician recorded age, sex, educational status, type of tooth
      extracted, dietary habits, oral hygiene, history of smoking and betel quid
      chewing and reasons for tooth extraction. A series of bivariate analyses and
      logistic regression analyses were carried out to assess the effects of major
      variables. RESULTS: A total of 868 teeth were extracted from 582 patients. Among
      them, 586 (67.5%) of the teeth were extracted due to caries and its sequelae, 161
      (18.5%) and 121 (13.9%) were extracted for periodontal and other reasons.
      Logistic regression analysis revealed that tooth extraction due to caries had
      significant associations with age (P = 0.0001), tooth type (P = 0.013),
      consumption of sweets, snacks and soft drinks (P = 0.0001 and P = 0.0001,
      respectively), frequency of teeth cleaning (P = 0.007) and dental attendance
      pattern (P = 0.004). For tooth extraction due to periodontal disease,
      associations with age (P = 0.001), educational level (P = 0.018), tooth type (P =
      0.024), betel quid chewing (P = 0.0001), smoking habit (P = 0.032), method of
      teeth cleaning (P = 0.001) and the use of dentifrices (P = 0.024) were
      statistically significant. CONCLUSIONS: In this group of patients, caries and its
      sequelae were the most common reasons for extraction of teeth, followed by
      periodontal disease. Betel quid chewing, smoking and dietary and oral hygiene
      habits were also significant predictors of tooth loss.

PMID- 19119575
TI  - Patients' views on periodontal disease; attitudes to oral health and expectancy
      of periodontal treatment: a qualitative interview study.
AB  - PURPOSE: The aim of the study was to explore and gain an understanding of
      patients' views on their periodontal conditions, their perceived impact of
      periodontitis on daily life, as well as their attitudes to oral health and
      expectations of treatment. MATERIALS AND METHODS: The study subjects were
      patients with chronic periodontitis, who had been referred to a specialist
      clinic. The constant comparative method for grounded theory was used to collect
      and analyse the data. Audiotaped, open-ended interviews were conducted after
      periodontal examination, but before treatment. The interviews were transcribed
      verbatim and consecutively analysed in hierarchical coding processes and
      continued until saturation was reached (n = 17). In the analysis, a conceptual
      model that outlined the steps involved in the diagnosis of periodontitis was
      generated. The core concept of the model, keeping up appearance and self-esteem,
      was related to the following four additional categories and their dimensions;
      doing what you have to do--trying to live up to the norm, suddenly having a
      shameful and disabling disease, feeling deserted and in the hands of an
      authority, and investing all in a treatment with an unpredictable outcome.
      RESULTS: The results illustrated that subjects diagnosed with chronic
      periodontitis felt ashamed and were willing to invest all they had in terms of
      time, effort and financial resources to become healthy and to maintain their self
      esteem. However, they perceived a low degree of control over treatment decisions
      and treatment outcome. CONCLUSIONS: The results demonstrate the vulnerability of
      patients diagnosed with chronic periodontitis and emphasise the importance of
      communication in dentistry.

PMID- 19119576
TI  - Periodontal status of green marble mine labourers in Kesariyaji, Rajasthan,
      India.
AB  - AIMS: The purpose of the present study was to assess the prevalence and pattern
      of periodontal disease among green marble mine labourers and to use the data to
      provide a baseline for planning and evaluation of oral health care. MATERIALS AND
      METHODS: The study area was located in the Udaipur district of Rajasthan, India,
      divided into four geographical zones: Masoron ki ovri, Rushabhdev, Khandiovri and
      Kagdar Bhatiya. This study comprised 513 male subjects in four age groups (18 to
      25, 26 to 34, 35 to 44 and > 45 years) collected using the stratified cluster
      sampling method. The data were collected by World Heath Organization (WHO) oral
      health assessment form, and clinical examination was conducted by the methods
      recommended by the WHO oral health surveys. There were three examiners, all of
      whom were calibrated before the survey for inter-examiner variability. The
      reliability was tested by means of weighted kappa statistics, which were 89% for
      periodontal data. Data were statistically analysed using SPSS/PC+ (SPSS software,
      Illinois, USA). RESULTS: The prevalence of periodontal disease was found to be
      98.2%. Bleeding on probing and calculus were widespread. The mean number of
      healthy sextants decreased abruptly with an increase in age. The greatest
      periodontal destruction was manifested in the 35 to 44-year-old age group, with
      0.4 sextants having deep pocket probing depths. CONCLUSIONS: The present level
      and pattern of periodontal disease in marble mine workers is severe, and the
      implementation of oral health promotion and prevention is urgently needed.

PMID- 19119577
TI  - Periodontal health status in pan chewers with or without the use of tobacco.
AB  - BACKGROUND: Betel nut and tobacco chewing is a common practice in south-east
      Asia. In India, betel nut is commonly chewed in the form of pan, with or without
      tobacco. Numerous studies have shown the carcinogenic potential of betel nut and
      tobacco. Betel nut and tobacco are also known to have deleterious effects on the
      oral tissues. PURPOSE: The aim of our study was to evaluate and compare the
      periodontal effects of pan chewing with or without the use of tobacco as an
      ingredient. MATERIALS AND METHODS: The periodontal status of 300 subjects (150
      subjects were pan chewers with tobacco and 150 subjects were pan chewers without
      tobacco) was evaluated using the community periodontal index (CPI). The subjects
      were selected by the stratified random sampling method. The oral hygiene status
      of the subjects was evaluated using the simplified oral hygiene index. RESULTS:
      CPI code-4, with a probing depth of 6 mm or more, was seen in 30% of pan chewers
      with tobacco compared with 7.3% of pan chewers without tobacco. It was found that
      pan chewers with tobacco had 4.7 times more risk of having pockets than pan
      chewers without tobacco. The higher codes of loss of attachment were seen in pan
      chewers with tobacco compared with pan chewers without tobacco. It was found that
      pan chewers with tobacco had 7 times more risk of having loss of attachment when
      compared with the pan chewers without tobacco. CONCLUSIONS: The results show
      higher incidence of periodontal diseases in pan chewers who use tobacco compared
      with pan chewers who do not use tobacco. Based on the results, it was concluded
      that, although betel nut has deleterious effects on the periodontium, the
      addition of tobacco leads to a synergistic effect between betel nut and tobacco
      on the periodontal tissues.

PMID- 19119578
TI  - Effectiveness of two mouth rinses solutions in arresting caries lesions: a short
      term clinical trial.
AB  - PURPOSE: To clinically evaluate the additional effect of adding 0.12%
      chlorhexidine digluconate (CHX) to a 0.05% sodium fluoride (NaF) mouth rinse in
      arresting active enamel caries lesions after 28 days. MATERIALS AND METHODS: A
      short-term double-blind clinical trial that included a total of 170 children,
      aged 11 to 15 years, with active smooth surface caries lesions (average 6.52) was
      conducted. The participants were enrolled and randomly distributed into two equal
      groups. Under the supervision of the research team, the children rinsed with a 15
      ml solution of either 0.05% NaF (G1) or 0.05% NaF + 0.12% CHX (G2) for 1 min/day
      for 28 days. A clinical examination was carried out at the beginning and at the
      end of the study with children who underwent supervised tooth brushing. A
      calibrated examiner, who was unaware of the treatment given to each subject,
      examined all smooth surfaces dried with compressed air, isolated and illuminated
      with a reflector. The surface was considered active (A) or arrested (I). The
      frequency of A or I surfaces was evaluated by calculating the difference between
      the number found at the beginning and at the end of the trial. RESULTS: No
      significant differences were detected between the two groups with respect to
      caries lesion surfaces at baseline (6.49 +/- 4.45 - G1, 6.55 +/- 4.23 - G2,
      respectively), nor were differences found when age and gender wer taken into
      consideration. Arrestment proportions were 84.4% (G1) and 85.3% (G2) (P = 0.71;
      not significant). CONCLUSIONS: Although both solutions showed high arrestment
      proportions, the addition of CHX did not improve the arrestment capacity of the
      NaF mouth rinse.

PMID- 19119579
TI  - Applicability of common methods for short time erosion analysis in vitro.
AB  - PURPOSE: Dental erosion can be measured by different methods. The aim of the
      present study was to check the applicability of common methods to determine
      initial erosive effects. MATERIALS AND METHODS: Enamel surfaces (4.5 mm2) were
      eroded in vitro by treatment with hydrochloric acid (pH 2, 2.3 and 2.6) for 5 to
      60 s or 240 s, respectively. Erosive effects were assayed with three different
      methods: Knoop's diamond indentation, profilometry and the determination of the
      dissolved calcium ions (Ca2+) in a colorimetric assay based on the arsenazo-III
      reaction. RESULTS: Erosive mineral loss of > 1 microm are measurable with
      profilometry. This corresponds to the erosive effects that occur after 60 s or
      more. Profilometric data yielded variance of up to 50%. Knoop's diamond
      indentation also showed some limitations: the depth of indentation reached a
      plateau after 30 to 120 s and the measurements showed variance of up to 85%. With
      the colorimetric assay, short time erosive effects occurring within 5 s could be
      assessed precisely and kinetically. The method allowed small amounts of 400 pmol
      Ca2+ per well to be quantified in small volumes with little variability.
      CONCLUSIONS: For evaluation and quantification of short time erosive effects, the
      colorimetric method is superior to diamond indentation and profilometry.

PMID- 19119580
TI  - Dental erosion in a road-side battery technician: case report and a review of the
      literature.
AB  - BACKGROUND: Tooth wear has been generally described as being caused by erosion,
      abrasion and attrition. Erosion is currently believed to be the major factor
      involved in tooth wear, and its contribution in the development of tooth wear may
      be increasing. Among the numerous causes of erosion, extrinsic factors are the
      most common. Damage of tooth tissue has been described in battery factory workers
      due to acidic aerosol, but this has not been reported among roadside 'battery
      technicians' who dispense acidic solutions with a pipette, and often taste it to
      determine its 'specific gravity'. CASE DESCRIPTION: A 24-year-old man was
      referred to the authors' clinic for management of his grossly damaged teeth after
      presenting for oral diagnosis. History and investigation pointed to extensive
      erosive lesion as a result of abnormal and prolonged use of lead-acid
      rechargeable battery solution in his workplace. CLINICAL IMPLICATIONS: These
      groups of workers are prone to severe dental erosion, thereby compromising their
      oral function and health. They are also prone to a range of illnesses, especially
      kidney disease, because the acid solution is significantly rich in dissolved
      lead. Therefore, medical referral for complete assessment is required when any of
      this group present with an unexplained associated illness.

PMID- 19119581
TI  - Collaborative practice.

PMID- 19119582
TI  - Getting to know your CRNBC workplace representatives. Interview by Monica Bisal.

PMID- 19119583
TI  - Assignment between nurses.

PMID- 19119584
TI  - The evolution of B.C.'s nurse practitioners. Interview by Monica Bisal.

PMID- 19119585
TI  - 'Legitimate objectives' may override college's ability to set and enforce
      registration standards.

PMID- 19119586
TI  - The melting pot.

PMID- 19119587
TI  - Life insurance for the HIV-positive applicant--are we there yet?

PMID- 19119588
TI  - Mitral valve repair: late mortality, favorable and unfavorable characteristics.
AB  - OBJECTIVES: Review late mortality experience associated with surgical repair of
      regurgitant myxomatous mitral valves. Identify mortality associated with
      favorable and unfavorable characteristics for surgical mitral valve repair (MVR).
      METHODS: Overall mortality associated with MVR reported by several North American
      centers since 1980 is assessed. Mortality from additional studies on MVR
      associated with favorable and unfavorable preoperative characteristics is also
      determined. Standard mortality methodology is used and expectant mortality
      determined from the appropriate population life tables. RESULTS: Averaged
      (weighted for numbers of entrants) overall morality ratios (MR) for MVR from the
      Mayo Clinic and University of Toronto at 5, 10, and 15 years were 106%, 113% and
      145%. Favorable characteristics included isolated posterior leaflet repairs (MR
      at 5, 10 and 15 years: 97%, 106% and 130%) and asymptomatic preoperative status,
      defined as New York Heart Association (NYHA) Functional Class I or II (MR at 5,
      10 and 15 years: 69%, 50% and 93%). Unfavorable characteristics included isolated
      anterior mitral leaflet repairs (MR: 202%, 212% and 188%) and preoperative
      symptomatic NYHA Functional Class III or IV (MR: 142%, 130% and 127%). When
      reoperation was required, mild or moderate underlying myxomatous degeneration was
      favorable, usually enabling re-repair (MR at 12 years: 77%). Reoperation when
      severe myxomatous degeneration was present usually required prosthetic valve
      insertion (MR at 12 years: 187%). Coronary artery bypass grafting done at the
      time of MVR demonstrates an associated minimal increase in late mortality.
      CONCLUSIONS: Surgical repair of myxomatous mitral valves produces durable long
      term results with mild to modest overall increases in mortality. Favorable
      preoperative characteristics may be associated with near standard mortality risk.

PMID- 19119589
TI  - Mortality experience in the elderly in the Impairment Study Capture System.
AB  - Using the dataset of the Impairment Study Capture System, we analyzed mortality
      experience and underwriting on policies issued at ages 70 and up. Policy issue
      dates were from 1990-1998 and observation ran from 5-12 years. There were 1430
      deaths in a total exposure of over 102,000 policy-years. Nearly two thirds of the
      total exposure was for females. Despite the use of expected mortality
      differentiated by smoking status, the mortality ratio for smokers was much higher
      than for nonsmokers. Both the type of underwriting (paramedical and medical
      compared to nonmedical and simplified) and the underwriting risk class confirmed
      the intended effects of underwriting. Variation of mortality ratio by duration
      after issue did not contradict the select period slope of the 2001 VBT.

PMID- 19119590
TI  - Comparative mortality in HIV-infected patients in Denmark, 1995-2005.
AB  - Excess mortality in patients infected with HIV has decreased markedly since 1995.
      The source article utilized for this abstract provides a very detailed follow-up
      (FU) of a cohort based on all patients treated for HIV infection in Denmark
      during the period, January 1, 1995 to May, 2005. The FU cohort consisted of 3990
      patients treated at 8 specialized clinics for HIV-infected patients incident in
      Denmark. The Danish Civil Registration System (CRS) provided a database for this
      FU study. Results are given for exposures, deaths, annual mortality and excess
      death rates by quinquennial age group for male (M), female (F) and M and F
      combined, and for groups positive or negative to Hepatitis C virus (HCV+ or HCV
      ). Excess mortality was estimated by matching each HIV patient to about 92
      uninfected persons in the general population and obtaining their "expected"
      mortality rates. The experience of the total cohort was divided into three groups
      according to years of entry: 1995-1996, 1997-1999, and 2000-2005. There were 970
      deaths observed in the HIV cohort in an exposure of 22,744 patient-years during
      1995-2005. Mean annual mortality rate, q, over the observation period increased
      from 30 per 1000 at age 25-30 years to 93 per 1000 in the oldest age group of 65
      70 years. For all ages combined, q was 47 per 1000 in males and 29 in females. In
      the 18% of cases that were HCV+ q was 54/1000/year, much higher than in the
      majority of cases who were HCV-, who had a q of 32/1000/year. The overall q for
      the entire cohort was 38/1000/year.

PMID- 19119591
TI  - Underwriting the presidents.
AB  - The United States has had 43 presidents. We examined whether they survive
      significantly longer or shorter than their contemporaries. We found that survival
      was better for presidents elected in the 1789-1841 and 1933-2001 periods (SMRs of
      0.7 and 0.6, respectively), but worse for those elected in 1845-1929 (SMR = 2.9).
      We also found increased mortality during the years lived in office (SMR = 1.4),
      but no increase in mortality after leaving office (SMR = 1.0).

PMID- 19119592
TI  - Baseline distribution and correlation analysis of hsCRP in an insurance applicant
      population.
AB  - Many clinical studies have shown that baseline levels of high sensitivity C
      reactive protein (hsCRP) in apparently healthy men and women are highly
      predictive of future risk of heart attack, stroke, sudden cardiac death, and the
      development of peripheral arterial disease. This paper presents an analysis of
      the baseline characteristics of our prospective study cohort. The intent of our
      prospective study is to determine whether hsCRP can be used to better classify
      risk for life insurance applicants already at risk for cardiovascular events, as
      well as those who are not. The possibility that low levels of hsCRP levels in
      otherwise healthy applicants might be associated with more favorable
      cardiovascular risk could allow this test to be used to more precisely stratify
      risk in the standard-or-better underwriting classifications. In this preliminary
      analysis, high sensitivity CRP appears to be weakly correlated with BMI, and
      perhaps triglyceride level in this cohort of insurance applicants. Somewhat
      surprisingly, in contrast to many published reports, hsCRP was not found to be
      correlated with other lipid measures (TC, HDL, LDL), dysmetabolic markers or
      smoking classification during the underwriting process. We plan to analyze
      mortality results as they evolve in the future.

PMID- 19119593
TI  - South Africa: the new world of disability.
AB  - Over the past 10 years, unique business imperatives in South Africa have led to
      innovative risk product design, some of which are still unfamiliar to the rest of
      the world. The main drivers are: the unique mix of first- and third-world
      societies in our country, and an energetic marketing force operating in an
      already highly saturated insurance market. As a result, new product design has
      become one of the most effective ways to grow new business volumes in this
      competitive environment. This article reviews some of the unique products
      available and their advantages, target markets and disadvantages. The products
      that are discussed include lump sum total and permanent disability benefits,
      extended critical illness products, cover for impairment of function as well as
      risk products for people living with HIV/AIDS.

PMID- 19119594
TI  - Neuromyelitis optica.
AB  - Neuromyelitis optica (NMO) is an uncommon central nervous system demyelinating
      disease that produces transverse myelitis and optic neuritis. Although commonly
      misdiagnosed as multiple sclerosis, a number of features can help differentiate
      the two entities, including the presence of NMO-IgG. Immunosuppressants are used
      to treat NMO, but the overall prognosis is poor.

PMID- 19119595
TI  - Diagnostic pitfalls in a scanned electrocardiogram.
AB  - Diagnostic accuracy in electrocardiogram (ECG) interpretation is important for
      medical directors. Both confirming and discarding the diagnosis of a specific
      abnormality may greatly influence the assessment of an applicant's mortality
      risk. In the insurance industry, an additional challenge for ECG interpretation
      is the increasing use of scanned images. This case study illustrates some of the
      pitfalls in the electrocardiographic interpretation of a common prognostically
      important ECG abnormality.

PMID- 19119596
TI  - Maffucci's syndrome.
AB  - Maffucci's syndrome is a rare congenital disorder characterized by enchondromas
      and venous malformations with significant malignant potential.

PMID- 19119597
TI  - [Expression and significance of Cu/ZnSOD and PLUNC protein in chronic sinusitis
      and nasal polyp tissue].
AB  - OBJECTIVE: To validate the expression of Cu/ZnSOD and PLUNC protein in chronic
      sinusitis and nasal polyp tissue by immunohistochemistry. METHOD: Thirty-four
      nasal polyps, 30 chronic sinusitis and 18 control cases were chosen. All samples
      were stained with SP immunohistochemical method to examine Cu/ZnSOD and PLUNC
      protein respectively. RESULT: (1) Interestingly, we found the positive intensity
      of Cu/ZnSOD and PLUNC protein were the same in one sample, and they were both
      expressed in nasal epithelium mucosae, glandular epithelium and goblet cells; (2)
      We calculated that the constituent ratio among nasal polyps, chronic sinusitis
      and normal nasal mucosa was significant difference (chi2 = 30.689, P<0.01). The
      positive intensity of nasal polyps was mainly "+", and the positive intensity of
      chronic sinusitis was mainly "+++", and the positive intensity of normal nasal
      mucosa was mainly "++". CONCLUSION: Both Cu/ZnSOD and PLUNC protein are important
      part of the innate defense mechanism in nasal mucosa. Once the nasal mucosa is
      irritated by infectious agents or chemical factors, nasal epithelium mucosae,
      glandular epithelium and goblet cells will proliferate reactively, and then
      produce antiinflammatory agents such as Cu/ZnSOD and PLUNC protein to defend
      inflammation.

PMID- 19119598
TI  - [Expression of SleX in nasal epithelium with chronic rhinosinusitis].
AB  - OBJECTIVE: To explore the expression of SleX in nasal epithelium in patients with
      chronic rhinosinusitis. METHOD: Nine nasal epitheliums from patients with chronic
      rhinosinusitis and 7 normal controls were stained with SleX antibody by
      immunohistochemistry, and its expression were analyzed. RESULT: Both nasal
      epithelial cells and neutrophils expressed SleX. Nearly 88.9% nasal epithelium
      from patients with chronic rhinosinusitis expressed SleX while 14.3% in normal
      control. Expression of SleX in nasal epitheliums from patients with chronic
      rhinosinusitis were higher than that in normal control. There were significant
      difference between two groups. CONCLUSION: Nasal epithelium from patients with
      CRS is highly expressed SleX. It may involve the occurrence of chronic
      rhinosinusitis.

PMID- 19119599
TI  - [Clinical significance of the expression of p53, p63 and p73 in nasal and
      paranasal sinus carcinoma].
AB  - OBJECTIVE: To study the clinical significance of the expression of p53, p63 and
      p73 protein and the correlation of p53 and p63 in nasal and paranasal sinus
      carcinoma (NPSC). METHOD: The immunohistochemical technique was used to detect
      the expression of p53, p63 and p73 in 67 cases of NPSC, para-cancer tissues and
      non-cancer tissues. RESULT: The positive rate of p53 and p63 protein in NPSC was
      significantly higher than that in park cancer tissues and non-cancer tissues
      (P<0.01), and there were a positive correlation between the expression of p53 and
      p63 protein in NPSC (P<0.01). But the expression of p73 had no significant
      difference among NPSC, para-cancer tissues and non-cancer tissues (P>0.05).
      CONCLUSION: There are positive correlation between p53 and p63 protein in NPSC,
      and they may play an important role in the tumorgenesis of NPSC. The p73 may not
      be associated with tumorgenesis of NPSC.

PMID- 19119600
TI  - [Application of acoustic rhinometry in assessment of preschool children nasal
      cavity volume].
AB  - OBJECTIVE: Acoustic rhinometry (AR) was performed to standardize the measurement
      techniques, result interpretation and reference values of nasal cavity volume
      (NV) in preschool children. METHOD: (1) Nasal cavity models were used to test the
      correlations between NV, minimal cross-sectional area (MCA), and nasal
      resistance. (2) There were 97 four-year-old and 137 five-year-old children
      underwent AR test. RESULT: (1) Model tests showed that resist the nce were better
      correlated with the change of volume than the MCA. (2) The average bilateral NV
      in preschool children was (2.03 +/- 0.4) ml. No significant gender and age
      difference were observed (P>0.05). CONCLUSION: Volume measurement appears more
      sensitive and reliable than the MCA in assessing nasal patency. The AR result
      interpretation and normative NV values in preschool children are introduced.

PMID- 19119601
TI  - [Application of frontal drill in revision endoscopic frontal sinus surgery].
AB  - OBJECTIVE: To discuss the application of frontal drill in revision endoscopic
      frontal sinus surgery. METHOD: The clinical data of 11 adult patients (18 sides)
      suffering from chronic recurrent frontal sinusitis were analyzed retrospectively.
      The patients received revision endoscopic frontal sinus surgery with frontal
      drill because of difficulty in confirming ostia under endoscope. Postoperatively
      all cases were followed up to evaluate the efficacy. RESULT: The ostia of frontal
      sinus were successfully opened with this method in all cases, and no serious
      complications occurred except hemorrhage due to injury of anterior ethmoidal
      artery in 1 case. After 7 to 35 months follow-up postoperatively, the symptoms
      vanished in all cases and none recurred. The endoscopic examinations showed well
      opening of frontal sinus ostia. CONCLUSION: Localization of frontal ostium with
      frontal drill is a simple, convenient, safe and effective accessorial method for
      revision endoscopic frontal sinus surgery.

PMID- 19119602
TI  - [Axillary flap approach to the frontal recess in 20 patients].
AB  - OBJECTIVE: To discuss the method and efficacy of Wormald technique application in
      opening frontal recess surgery. METHOD: Twenty cases with chronic frontal
      sinusitis underwent surgery with Wormald technique were subjected to this study.
      Preoperative CT scan and especially sagittal reconstructing were used to indicate
      the extent of lesion, source and key adjacent structure. RESULT: All patients
      were followed up for more than half a year with an average of nine months. The
      effective rate was 90% and no recurrence appeared except for two cases.
      CONCLUSION: Application of Wormald technique for frontal recess open surgery
      under endoscope is safe and feasible, with no intracranial, orbital, and other
      serious complications. All treatments including preoperative sagittal CT, that
      help to a clear locating the cell lead to the frontal recess obstructive lesions,
      awarding of the potential difficulties while frontal recess could not be
      identified, protecting mucous membrane in operation, and strengthening
      medication, washing, and oxygen spray after operation, can improve operational
      efficiency.

PMID- 19119603
TI  - [Diagnosis of small round cell tumor of nasal sinus and bases of skull (a report
      of 123 cases)].
AB  - OBJECTIVE: To investigate the features and diagnosis way of small round cell
      tumor of nasal sinus and bases of skull. METHOD: A retrospective analysis of 123
      case with small round cell tumor of nasal sinus and bases of skull were carried
      out in our hospital in past ten year. Clinical, histological, radiological and
      immunohistochemical characters of these cases were studied. RESULT: All cases
      usually complained of nasal obstruction, headache, diplopia, nasal mucus with
      bleeding, vision or weight loss. Expansible or infiltrative lumps were found in
      nasal sinus or bases of skull in radiological examination. A lot of small round
      cells were found in these tumors in histological pathology. At least 5-6 cell,
      tissue or tumor markers were examined immunohistochemically in most of cases
      before the final diagnosis were made. In some cases over 20 markers were
      examined. Five cases were carried out transmission electron microscope
      examination, special features such as desmosome and myofilament were found.
      CONCLUSION: Clinical symptom, physical signs and radiological finding can supply
      malignant evidences of these tumors. Histological examination can make certain
      that they are small round cell tumors, but final diagnosis is still hard to make
      only by these. Immunohistochemical examination of various markers can tell the
      original characters of the specimen tissues, it is the key for final diagnosis.
      Transmission electron microscope examination is another helpful way for
      diagnosis.

PMID- 19119604
TI  - [Enhancement of radio sensitivity in nasopharyngeal cancer cells by the own
      regulation of VEGF expression after adenovirus-E1A gene therapy].
AB  - OBJECTIVE: To determine the effect of Ad-E1A gene therapy on the radiosensitivity
      of nasopharyngeal carcinoma cell by downregulating the expression of VEGF in
      vitro. METHOD: The human nasopharyngeal carcinoma CNE-2Z cell lines were
      investigated. The recombinant adenovirus vector containing E1A gene was used for
      this study. After CNE-2Z cells was treated with PBS, Ad-beta-gal and Ad-E1A for
      48 h, the three groups were irradiated in different doses at 0, 2.4, 6, 8 and 10
      Gy, the cytotoxicity was determined by MTT assay and cell cycle was analysis by
      flow cytometry. The VEGF expression were evaluated by RT-PCR assay and
      immunocytochemical analysis. RESULT: Significant cell deaths by IR were observed
      in a dose dependent manner in the three group CNE-2Z cells. After transduction of
      the E1A gene into CNE-2Z cells, the sensitivity of these cells to radiation was
      enhanced than the PBS treated group and Ad-beta-gal treated group. Cell growth
      inhibition in Ad-E1A group by IR was strongly enhanced than Ad-beta-gal treated
      group and PBS treated group. RT-PCR assay and immunocytochemical analysis showed
      VEGF expression was downregulated in Ad-E1A treated group. CONCLUSION: E1A gene
      therapy can effectively enhance the nasopharyngeal carcinoma cell sensitivity to
      the radiotherapy by down-regulating VEGF expression. These findings may pave the
      way for efficient radiation-gene therapy to NPC in future.

PMID- 19119605
TI  - [Expression of clara cell 10-KDa protein in murine bacterial chronic
      rhinosinusitis model].
AB  - OBJECTIVE: To investigate the expression of Clara cell 10-KDa protein (CC010) in
      sinonasal mucosa of murine bacterial chronic rhinosinusitis (BCRS) model. METHOD:
      A murine BCRS model was established by Streptococcus pneumoniae inoculation plus
      Merocel ostiomeatal obstruction. After 12 week's intervention, histological
      changes of sinonasal mucosa in BCRS model were examined by hematoxylin and eosin
      stain, periodic acid-schiff stain, and Masson-Trichrome stain. The mRNA and
      protein expression of CC10 in sinonasal mucosa were determined by reverse
      transcription polymerase chain reaction and immunohistochemistry methods. The
      number of CC10 positive cells in sinonasal epithelium was also counted. RESULT:
      In BCRS model group, polymorphonuclear neutrophils (PMN), subepithelial collagen
      deposition, goblet cells, and epithelial thickness were significantly increased,
      compared with control group (P<0.01). However, CC10 positive cells, CC10 mRNA and
      protein expression in sinonasal mucosa of BCRS model group were significantly
      decreased, compared with control group (P<0.01). Moreover, the number of CC10
      positive cells was significantly negatively correlated with PMN (r=-0.734,
      P<0.01), subepithelial collagen deposition (r=-0.776, P<0.01), epithelial goblet
      cells (r=-0.841, P<0.01), and epithelial thickness (r=-0.805, P<0.01),
      respectively. CC10 average grayscale value was significantly positively
      correlated with PMN (r=0.771, P<0.01), subepithelial collagen deposition
      (r=0.802, P<0.01), epithelial goblet cells (r=0.887, P<0.01), and epithelial
      thickness (r=0.855, P<0.01), respectively. CONCLUSION: The expression of CC10 is
      downregulated in sinonasal mucosa in BCRS model. As an important endogenous
      modulin, CC10 might play a crucial role in the pathogenesis of chronic
      rhinosinusitis.

PMID- 19119606
TI  - [Fibrous dysplasia involving sphenoid and occipital bone: one case report and
      literature review].
AB  - OBJECTIVE: To study the clinical manifestation, radiograph features, pathology,
      diagnosis and treatment of fibrous dysplasia in cranial bone. METHOD: A case of
      fibrous dysplasia involving sphenoid and occipital is reported and literature
      were reviewed. RESULT: The most common complaint were headache, proptosis,
      diplopia, or visual changes. Distinguishing features of fibrous dysplasia on CT
      include "ground-glass" appearance, bone fiber anisotrophy, aneurysmal bone cyst
      formation and thickness of the cranial cortices. Fibrous dysplasia could be
      exactly diagnosed by pathology. Computed tomography was also a choice for
      diagnosis. CONCLUSION: Fibrous dysplasia involving the cranial bone can present
      in myriad ways. Modern imaging modalities and histopathologic analysis is
      required to make accurate diagnosis. Surgery, particularly in a challenging
      region such as sphenoid and occipital bone, should preserve the existing function
      for the patients with functional impairment or a cosmetic deformity.

PMID- 19119607
TI  - [An eclectic pharmacologist brought up by times and environment].

PMID- 19119608
TI  - [Reward, homeostasis and the habenula].
AB  - Reward is the behavior that inspires the subject to engage in various forms of
      behavior for survival and reproduction. Reward prediction, reward prediction
      error and the brain processes induced by them are necessary for the homeostasis
      with the fine regulations. These processes are closely involved in the activity
      of dopamine neurons in the brain. Lateral habenula regulates the activity of
      dopamine neurons in the midbrain. Lateral habenula neurons are excited while the
      unpredictable reward exists, and the dopamine neurons are strongly inhibited.
      Homeostasis sustained is the goal of the functional regulation of the living
      body. Reward is the driving power of forcing the living body to achieve
      homeostasis. Habenula can independently perform the reward function. And it also
      participates in the regulations of the major physiological functions. Therefore
      habenula may also be one of the center in the brain of homeostatic regulation.

PMID- 19119609
TI  - [Roles of ventrolateral orbital cortex in pain modulation and acupuncture
      analgesia].
AB  - The ventrolateral orbital cortex (VLO) is a major component of orbital cortex,
      which has extensive connections with periaqueductal gray (PAG), thalamus and
      other cortical regions. Researches suggest that the VLO is involved not only in
      nociception, but also in pain modulation, through activation of PAG brainstem
      descending antinociceptive pathway to inhibit the nociceptive inputs at the
      spinal/trigeminal level. Furthermore, many results demonstrate that opioid, 5-HT,
      GABA and their receptors are involved in the VLO antinociception. VLO plays an
      important role in acupuncture analgesia. In this review we summarized the roles
      of ventrolateral orbital cortex in pain modulation and acupuncture
      antinociception.

PMID- 19119610
TI  - [Role of GATA-4 in cardiac development and remodeling].
AB  - GATA-4 plays important roles in the process of cardiac development and
      remodeling. Deletion or mutation of GATA-4 is associated with malformation of
      cardiac development directly, even embryolethality. Down-regulation of GATA-4 may
      lead to deterioration of cardiac function. GATA4 activity is significantly
      changed by pathological stimulation induced by pressure overload, hypoxia,
      sympathetic nerve activation, etc. It involves in the process of myocardium
      remodeling through regulating ANP, BNP, Bcl-2, CARP, etc. Overall, GATA-4 has
      important roles in the process of cardiac development and remodeling. Exploration
      of underlying mechanism of GATA4 transcriptional regulation may provide a new
      clue for the prevention and treatment of cardiovascular diseases.

PMID- 19119611
TI  - [Research advances in Th17 cells].
AB  - CD4+ T cells have been divided into different subsets, essentially based on the
      cytokines they produce. These subsets include T helper cell (Th)1, Th2 and
      regulatory T cells (Treg). Recently, another subpopulation of T cells has been
      identified, and it was named as Th17, which is characterized by the release of
      interleukin (IL)-17. The discovery of Th17 cells is not only a challenge to some
      traditional theories, such as the differentiation of CD4+ T cells and the drift
      theory of Th1/Th2, but also provides new research approach to inflammatory and
      immunologic diseases, especially, the balance among Th1, Th2, Treg and Th17 cells
      may play an important role in maintaining the normal immune response.

PMID- 19119612
TI  - [Transcription regulation by histone-modifying enzymes].
AB  - During gene transcription, it needs to recruit many histone-modifying enzymes to
      modify histone. These chemical modification contains methylation, acetylation,
      phosphorylation, ubiquitylation, sumoylation of histone and so on. Most of
      histone-modifying enzymes can form a complex with various transcriptional
      factors, they can change the interaction between histone and DNA, which regulate
      gene transcription. This review is focused on recent findings regarding the
      composition, the structure and the function of the histone-modifying enzyme
      complexes.

PMID- 19119613
TI  - [Involvement of post-receptor signal transduction in alcohol addiction].
AB  - Alcohol abuse and addiction is not only a severe social problem, but also an
      important biological medical issue. Studies in neuropsychopharmacology and
      molecular neurobiology indicate that neurotransmitters and its receptors play
      important roles in alcohol abuse and addiction, and post-receptor signal
      transduction pathways, including cyclic adenosine 3', 5'-monophosphate (cAMP)
      protein kinase A (PKA), phosphoinositide (PI), Ca2+ -calmodulin (CAM),
      phospholipase D (PLD) and tyrosine kinase Fyn signaling cascade. In this review,
      works on post-receptor signal transduction involved in alcohol addiction are
      systematically presented and summarized.

PMID- 19119615
TI  - [The updated advancements in theta oscillations in the hippocampus].

PMID- 19119614
TI  - [Acupuncture for the treatment of drug addiction].
AB  - Over the last three decades there has been an increasing interest in acupuncture
      treatment of substance abuse around the world. Three important steps can be
      identified in this field. Dr. H. L. Wen of Hong Kong was the first (1973) to
      report that acupuncture at 4 body points and 2 ear points combined with
      electrical stimulation can relieve opiate withdrawal signs in the addicts. The
      second major step was made by Dr. M. Smith in New York, the head of the National
      Acupuncture Detoxification Association (NADA) of the U.S.A., who finalized a
      protocol (1985), using only ear points without electrical stimulation for the
      treatment of drug abuse. The recent advance in this field was made by Prof. J. S.
      Han and his colleagues in Neuroscience Research Institute of the Peking
      University, Beijing, who characterized a protocol (1992- ), using electrical
      stimulation of identified frequencies on body points to ameliorate heroin
      withdrawal signs and prevent relapse to heroin use. In this review, the efficacy
      of acupuncture and related techniques for the treatment of drug dependence in
      experimental settings and clinical practice will be reviewed, and the possible
      mechanisms underlying this effect be discussed.

PMID- 19119616
TI  - [Peroxisome proliferators-activated receptor gamma and organ fibrosis].

PMID- 19119617
TI  - [The role of PANDER in the pathogenesis of diabetes].

PMID- 19119618
TI  - [Developmental regulation of sleep/wake cycles in rats].

PMID- 19119619
TI  - [Advances in the study of splicing variants of GLT-1].

PMID- 19119620
TI  - [The mechanisms of glutamate released from astrocytes].

PMID- 19119621
TI  - [Progress in studies of green tea polyphenols on neurodegenerative diseases].

PMID- 19119622
TI  - [Role of hydrogen sulfide in the hypoxia pulmonary hypertension].

PMID- 19119623
TI  - [Progress in regulation of FoxO on cell proliferation, differentiation and
      apoptosis].

PMID- 19119624
TI  - [Research progresses of the neurobiology mechanism of delayed onset muscle
      soreness].

PMID- 19119625
TI  - [The research progress of phosphatase PTEN in central nervous system].

PMID- 19119626
TI  - [cAMP response element binding protein: convergence of antidepressant signaling
      cascades].

PMID- 19119627
TI  - [Signal transduction modulating pulmonary microvascular endothelial
      permeability].

PMID- 19119628
TI  - [Advances of Smad protein in the heart].

PMID- 19119629
TI  - [Effects of genistein on expression of TGF-beta1 and intracellular free Ca2+
      concentration in fibroblasts derived from human hypertrophic scar].
AB  - OBJECTIVE: To observe the effects of Genistein on TGF-beta1 expression and the
      intracellular free Ca2+ concentration in human hypertrophic scar fibroblasts, and
      to discuss the mechanism of the anti-fibrosis effect. METHODS: Fibroblasts were
      derived from human hypertrophic scar tissue and cultured in vitro. Genistein in
      different concentrations (25, 50, 100 micromol/L) was administrated to the
      fibroblasts, respectively. After 48 hours of co-culture, the expression of TGF
      beta1 mRNA and protein were examined by RT-PCR and Western-Blot assay
      respectively. The intracellular free Ca2+ concentration in hypertrophic scar
      fibroblasts pretreated by Genistein was determined by laser confocal scanning
      microscopy with or without the stimulation of bFGF. RESULTS: Genistein inhibited
      the expression of TGF-beta1 in hypertrophic scar fibroblasts on a concentration
      dependent manner. bFGF significantly elevated the intracellular free Ca2+
      concentration, however its stimulating effect was remarkably alleviated when the
      fibroblasts were pre-treated by Genistein. CONCLUSIONS: Genistein can reduce the
      expression of TGF-beta1 and block the accumulation of intracellular free calcium
      induced by growth factors. It maybe one of the possible mechanisms of Genistein's
      antifibrosis effect.

PMID- 19119630
TI  - [The expression of fibrillin 1 in pathologic scars and its significance].
AB  - OBJECTIVE: To probe into the mechanism of fibrillin 1 in pathologic scar, by
      examining the expressions of fibrillin 1 and TGF-beta1 as well as their
      correlations in the tissues of keloid, hypertrophic scar and normal skin.
      METHODS: The tissues of keloid, hypertrophic scar and normal skin were tested. RT
      PCR was used to assess the mRNA expression levels of the aimed genes. The
      distribution of fibrillin 1 in scars and normal skin was examined by
      immunohistochemistry staining. RESULTS: The mRNA level of fibrillin 1 in keloid
      (0.802 +/- 0.116) was increased by 218.25% (P < 0.01) than that in normal skin
      (0.252 +/- 0.067). The expression of the gene in hypertrophic scar (0.628 +/-
      0.144) was higher by 149.21% (while, P > 0.05) than that in normal skin. The
      expression of TGF-beta1 in keloid and hypertrophic scar were more than that in
      normal skin. The expression of fibrillin 1 was related to that of TGF-beta1
      positively (r = 0.820, P < 0.01). Fibrillin 1 protein was stained positively in
      basic membranes, endothelial cells, fibroblasts and extracellular matrix of skin
      tissues. In dermal, the protein levels of fibrillin 1 in keloid (0.117 +/- 0.042)
      was decreased than those in normal skin (0.185 +/- 0.043) and hypertrophic scar
      (0.181 +/- 0.048), the inhibition rates were 36.76%, 35.36% respectively (both P
      < 0.01). CONCLUSIONS: The expression of fibrillin 1 in keloid was changed and
      related to the expression of TGF-beta1 positively, which appears that fibrillin 1
      was a cicatrix specific gene. Fibrillin 1 might play an important role in the
      formation of keloid.

PMID- 19119631
TI  - [The significance and characteristics of distribution of beta-endorphin and mu
      opioid receptors in normal skin and hyperplastic scar].
AB  - OBJECTIVE: To detect the distribution of beta-endorphin and mu-opioid receptors
      (MOR) in normal skin tissue and scar tissue from healthy volunteers and patients
      with hypertrophic scar. METHODS: Normal skin samples from 10 healthy individuals
      and 10 patients with hypertrophic scar, and scar samples from the same 10
      patients were investigated. The beta-endorphin and MOR protein in the samples
      were detected by immunofluorescence (IF). The reverse transcription polymerase
      chain reaction (RT-PCR) was used to detect MOR mRNA. RESULTS: Beta-endorphin and
      MOR protein were expressed in all samples. There were no significant differences
      in the expression of beta-endorphin and MOR protein between normal skin from
      healthy volunteers and patients with hypertrophic scar (P > 0.05). The expression
      of beta-endorphin, MOR protein and mRNA in hyperplastic scar was significantly
      stronger than that in normal skin (P < 0.01). CONCLUSIONS: The expression of beta
      endorphin and MOR is different in normal skin and hypertrophic scar. This maybe
      the possible reason of scar paresthesia.

PMID- 19119632
TI  - [Surgical management of type II orbital neurofibromatosis].
AB  - OBJECTIVE: To study the clinical manifestations and surgical treatment of Type II
      orbital neurofibromatosis. METHODS: From Jan, 2001, to Oct, 2006, clinical data
      of 16 cases with type II orbital neurofibromatosis were retrospectively analyzed
      in the Department of Ophthalmology, Ninth People's Hospital, Medical School of
      Shanghai Jiao Tong University. RESULTS: All patients had orbito-temporal or intra
      orbital neurofibromatosis, combined with periorbital deformities. After partial
      tumor resection, the orbital reconstruction and blepharoplasty were performed in
      the same stage. The patients were followed up for 6-12 months with no relapse.
      The vision was improved in 6 cases and kept the same in 10 cases. The cosmetic
      results were satisfactory in all cases. 5 cases were re-operated because of
      relapse of blepharoptosis. CONCLUSIONS: The function and appearance can be
      markedly improved after one-stage partial tumor resection, orbital reconstruction
      and blepharoplasty in patients with type II orbital neurofibromatosis.

PMID- 19119633
TI  - [Research and clinical application of computer-aided design of craniofacial
      prosthesis using mirror technique].
AB  - OBJECTIVE: To explore the feasibility of creating a 3D-CAD model of craniofacial
      prostheses through mirror technique to repair the unilateral craniofacial defects
      and restore craniofacial symmetry. METHODS: Patients with unilateral craniofacial
      defects underwent spiral CT scanning. CAD3-D image was reconstructed ad 3-D CAD
      model of craniofacial prosthesis was created with mirror technique, Boolean
      operation and rapid prototyping technique. Then the prosthesis made of bioactive
      artificial bone was made through plaster cavity block. RESULTS: 15 cases were
      treated with no complications. Good symmetry was achieved after operation.
      CONCLUSIONS: Designing the craniofacial prosthesis with mirror technique
      guarantees excellent functional and cosmetic results for repairing the unilateral
      craniofacial defects.

PMID- 19119634
TI  - [Significance of ramus measurement through computed tomography in the sagittal
      split osteotomy of the ramus].
AB  - OBJECTIVE: To investigate significance of the distribution and thickness of
      cancellous and cortical bone in the mandibular ramus using computed tomography
      (CT) in the design of osteotomy at the medial aspect of the ramus. METHODS: 45
      cases with class III prognathism underwent CT before operation. The distribution
      and thickness of cancellous and cortical bone in the mandibular ramus was
      measured every 2.5 mm thick from mandibular lingular plane to 20 mm above it.
      RESULTS: The upper ramus was separated by cancellous bone in only 37.5% of the
      cases. The other cases had no cancellous bone in the upper ramus. 5 mm above the
      lingual, the thickness of cortical bone at the lingual aspect decreased from the
      front to the behind with an average thickness of 1.55 mm. The distance from
      lingual to the fusion at the posterior border of ramus was 9.45 mm. CONCLUSIONS:
      The medial cortical osteotomy should be located within 5 mm above the lingual and
      within 9.45 mm posterior to the lingular. The osteotomy could be slightly oblique
      and become deeper from behind to the front with an average depth of about 2 mm.

PMID- 19119635
TI  - [3-Dimensional CT for preoperative measurement and postoperative assessment in
      craniosynostosis].
AB  - OBJECTIVE: To investigate the significance of 3-dimensional (3-D) CT for
      preoperative measurement and postoperative assessment in craniosynostosis.
      METHODS: 17 cases with craniosynostosis underwent 3-D CT reconstruction. The 3-D
      images were used to perform cephalometry. The cases included brachycephalic,
      caphocephalia, plagiocephaly. The CVAI must be measured for plagiocephaly.
      Measurement results were compared before and after operation in 9 cases. RESULTS:
      The bone segments were advanced 1.5 - 3 cm in brachycephalic, retruded 2 - 4 cm
      in scaphocephalic, moved back and forth about 2 cm in plagiocephaly. CONCLUSIONS:
      Preoperative 3-D CT reconstruction and measurement can be used to design the
      advancement distance of bone flap and orbito-frontal bone bridge, as well as to
      estimate the treatment results before operation.

PMID- 19119636
TI  - [Significance of location of mandibular canal by 3-dimensional CT in the
      mandibular angle osteotomy].
AB  - OBJECTIVE: To decrease the incidence of inferior alveolar neurovascular bundle
      injury through location of mandibular canal by 3-dimensional (3-D) CT. METHODS:
      30 female cases with prominent mandibular angle underwent 3-D CT before
      operation. The 3-D images were used to measure the distances between upper points
      of lower teeth to the inferior border of the canal. Then the osteotomy was
      designed according to the canal position to avoid the inferior alveolar
      neurovascular bundle injury. The canal protection was observed intraoperatively
      and postoperatively. RESULTS: The mandibular canal was protected very well in all
      30 cases without any injury to the inferior alveolar neurovascular bundle.
      CONCLUSIONS: The 3-D CT can accurately locate the mandibular canal to guide the
      design of the mandibular angle osteotomy for patients with prominent mandibular
      angle.

PMID- 19119637
TI  - [Early reconstruction of the periorbital injuries].
AB  - OBJECTIVE: To study the clinical characteristics and the treatment of periorbital
      injuries. METHODS: 61 cases were treated, including 30 cases orbitozygomatic
      fracture, 6 cases of frontal-orbital fracture, 8 cases of naso-ethmoid-orbital
      fracture, 7 cases of blow -out fracture and 10 cases of complicated fracture. The
      patients were diagnosed after physical examination and other examination, like
      CT. Through bicoronal or local mini incision at the end of eyebrow, combined with
      subciliary incision and local wound approach, the fractured sites were exposed
      completely. Then the fractured fragments were repositioned and fixed rigidly. The
      orbital wall was reconstructed with titanium net and Medpor. RESULTS: The wounds
      healed primarily. Good cosmetic and functional results achieved in most of the
      patients. 4 cases underwent second-stage ophthalmectomy. 2 patients had diplopia
      after operation, but improved gradually. 3 cases of blepharoptosis needed further
      treatment. CONCLUSIONS: Early diagnosis and treatment is very important for
      periorbital injuries. Fracture reposition and orbital wall reconstruction should
      he performed at early period.

PMID- 19119638
TI  - [Clinical study of chest contour deformity after harvesting of costal cartilage
      for total ear reconstruction].
AB  - OBJECTIVE: To investigate the chest contour deformities after harvesting of
      costal cartilage for total ear reconstruction, so as to prevent donor site
      morbidity. METHODS: 107 cases of microtia who underwent ear reconstruction with
      costal cartilage during the period from 1994 to 2003, were retrospectively
      studied. Both the chest depression deformity and the costal arch deformity were
      evaluated. The possible related factors to the chest contour deformities were
      analyzed statistically with Stata software. RESULTS: The incidence of chest
      depression was 54.55% (48/88), including 35 cases of mild depression (39.77%) and
      13 cases of severe depression (14.77% ). The incidence of costal arch deformity
      was 52.77% (46/88), including 33 cases of mild deformity (37.50%) and 13 cases of
      severe deformity (14.77%). The incidence of both deformities was significantly
      different at different age (P < 0.01), but not at different follow-up period (P =
      0.294 and P = 0.225, respectively). Gender was related to the incidence of chest
      depression (P < 0.01), but not to the costal arch contour deformity (P = 0.619).
      Comparing resection of the 6th and 7th rib cartilage with resection of 7th and
      8th rib cartilage, the incidence of costal arch deformity was significantly
      different (P < 0.01), but the incidence of depression deformity was not (P =
      0.657). CONCLUSIONS: The incidence of chest deformities increases with early
      operation time (< 13 years old). The male patients have higher incidence of
      depression deformity than female. The arch deformity is higher when the 6th and
      7th rib cartilage were resected. The follow-up period is not related to the chest
      deformities.

PMID- 19119639
TI  - [Repair of large defects in upper extremities with pedicled combined flap].
AB  - OBJECTIVE: To explore the flap transposition for repairing large defects in upper
      extremities. METHODS: 12 cases with large defects in elbow, forearm, wrist or
      palm caused by high-voltage electricity, hot-pressure or crush, were treated. 4
      cases were treated with latissimus dorsal myocutaneous flaps combined iliolumbar
      flaps. 2 cases were treated with latissimus dorsal myocutaneous flaps combined
      lateral thoracic flaps. 6 cases were treated with large combined thoracic-abdomen
      flaps. RESULTS: All the flaps survived except for one flap with 2 cm distal
      necrosis and sub-flap infection. Satisfactory results were achieved. CONCLUSIONS:
      Early debridement and reconstruction with pedicled combined flaps are feasible
      and reliable for large defects in the upper extremities.

PMID- 19119640
TI  - [3-Dimensional reconstruction of MRI in patients with polyacrylamide hydrogel
      injection for augmentation mammoplasty].
AB  - OBJECTIVE: To investigate the effective diagnostic method for the patients with
      polyacrylamide hydrogen injection for augmentation mammaplasty. METHODS: MRI
      scanning (layer thickness 1mm, t2 _ ps3d_ cor alignment) was performed on 23
      patients with polyacrylamide hydrogen injection for augmentation mammaplasty. The
      data were imported into computer and processed. 3D reconstruction and analysis
      modules were run subsequently to do the volume reconstruction and surface
      reconstruction to obtain stereoscopic images of the gel and adjacent structures
      in virtual reality, and to calculate the volume of the hydrogel. RESULTS: Among
      the 23 patients (46 breasts), the injected hydrogel with integrity capsule
      existed in retromammary space with no malposition in 5 cases (10 breasts). The
      capsule was not integrally formed and hydrogel was separately distributed with
      irregular edge in 6 patients (12 breasts). The pectoris major space, subcutaneous
      and gland invasion was found in 11 patients (22 breasts). Small amount of
      hydrogel sparsely distributed in mammary gland and degenerative muscular tissue
      in 1 patient (2 breasts) who had received extracting surgery before. The volume
      of hydrogel ranged from 220.309 ml to 372.371 ml (mean: 306.328 ml) in 22
      untreated patients (44 breasts). CONCLUSIONS: The volume and distribution of
      hydrogel can be known clearly by 3D MRI reconstruction technique. This feasible
      technique is helpful in removing the hydrogel completely.

PMID- 19119641
TI  - [Cephalometry of Li people through 3-dimensional CT].
AB  - OBJECTIVE: To investigate the skull characteristics of the Li people in Hainan
      through 3-D CT. METHODS: CT scan and 3-D reconstruction are very helpful for the
      cephalometry including the distance and angle measurement. The image can also be
      enlarged to make the measurement more precisely. 80 Li volunteers underwent the
      cephalometry through 3-D CT. The data were analyzed and compared with those an
      people. RESULTS: The results showed difference between the genders of Li people.
      Compared with Han people, Li people has their own facial characteristics, such as
      wider face and wider orbital distance. CONCLUSIONS: Cephalometry through 3-D CT
      can show the skull characteristics precisely. The data in this study has great
      significance in craniomaxillofacial surgery and ethnology.

PMID- 19119642
TI  - [Preliminary study of constructing tissue-engineered cartilage with the
      endoskeletal scaffold of HDPE by bone marrow stromal cells].
AB  - OBJECTIVE: To explore the feasibility of using a nonreactive, permanent
      endoskeletal scaffold to create the prothesis in special shape which is covered
      with tissue-engineered cartilage. METHODS: Porcine BMSCs and articular
      chondrocytes were isolated and expanded respectively in vitro. Porcine BMSC of
      passage 1 in the concentration of 10 x 10(7)/ml were seeded onto a cylinder
      shaped PGA (1 mm in thickness)/Medpor (3mm in diameter and 5mm in highness)
      scaffold as the experimental group. After the cell-scaffold constructs were
      cultured for 5 days, the primary medium, high-glucose DMEM medium with 10% fetal
      bovine serum (FBS), was replaced by chondrogenically inductive medium for 4
      weeks. BMSCs and chondrocytes of the same concentration were seeded respectively
      onto the scaffold as the negative control group and the positive control group.
      After cultured in vitro for 4 weeks, the cell-scaffolds construct were implanted
      into subcutaneous pockets on the back of nude mice. Four and eight weeks later,
      the formed cartilage prosthesis were harvested and then evaluated by gross view,
      histology, immunohistochemistry and glycosamino-glycan (GAG) content. RESULTS:
      Cells in all groups had fine adhesion to the scaffold and could secrete
      extracellular matrix. All specimens in experimental group and positive control
      group formed mature cartilage with collagen II expression.The mature catrtilage
      wraped HDPE compactly and grown into the gap of HDPE. Mature lacuna structures
      and metachromatic matrices were also observed in these specimens. GAG contents in
      experimental group were (5.13 +/- 0.32) mg/g (4 weeks), (5.37 +/- 0.12) mg/g (8
      weeks). In contrast, specimens in BMSC group showed mainly fibrous tissue.
      CONCLUSION: It indicates that it is feasible to create special shaped tissue
      engineering cartilage with the permanent internal support using BMSCs as seed
      cell.

PMID- 19119643
TI  - [Molecular clone of adipose-derived stromal cells with high potential of
      adipogenic differentiation].
AB  - OBJECTIVE: To investigate the surface markers of adipose-derived stromal cells
      (ASCs) with high potential of adipogenic differentiation for increasing
      efficiency of adipose tissue engineering with selected seeds cells. METHODS: ASCs
      were harvested from human adipose tissue by collagenase digestion. After
      proliferation and adipogenic induction of ASCs, the mature induced adipocytes
      floating in the induction medium were collected. Ceiling culture was used to
      culture adipocytes and then dedifferentiated adipocytes was obtained at the
      ceiling. The reproductive activity, adipogenic differentiation potency and
      expression of surface markers were compared between the dedifferentiated
      adipocytes and ASCs. RESULTS: The reproductive activity between the
      dedifferentiation adipocytes and ASCs were similar. The potential of adipogenic
      differentiation of the dedifferentiated adipocytes was stronger than that of the
      ASCs. The expression of cell surface markers of both cells were almost the same.
      But the CD54 positive expression in dedifferentiated adipocytes was higher than
      that in ASCs. CONCLUSION: The CD54 expression maybe closely associated with high
      potential of adipogenic differentiation of dedifferentiated adipocytes. CU54
      maybe the specific identification of cell surface marker of ASCs with high
      adipogenic differentiation.

PMID- 19119644
TI  - [Study of adipose tissue engineering with human adipose-derived stem cells and
      collagen type I scaffold].
AB  - OBJECTIVE: To explore the possibility of building tissue-engineered adipose
      tissue and looking for a new approach for the repair of soft tissue defects.
      METHODS: The cells using enzymatic digestion from human liposuction part of the
      lipid extract were used as adipose tissue-derived cells and labeled with DiI
      fluorescent marker, the induced group using I collagen scaffold material as a
      carrier, the induced cell were planted into left back subcutaneously in nude mice
      at 1 x 10(7)/ml cell density, in the uninduced group cells were not induced by
      any, in the same cell density and type I collagen scaffold composite inoculated
      in nude right mouse back skin, the blank control group I collagen scaffold gaps
      in nude mice inoculated subcutaneously center of the neck, each of the six mice;
      Remove implants after 12 weeks and judge the adipogenic capacity through general
      and fluorescence microscopy, wet - determination, histological detection and oil
      red O staining qualitative. RESULTS: The primary source of fat cultured stem
      cells, similar to the fibroblast morphology, and has a strong proliferative
      capacity. In the role of adipose differentiation medium, it can be the mature fat
      cells in which cytoplasmic lipid droplets gather, oil red O staining was
      positive. In the induced group, newborn tissue were found in the experimental
      groups of nude mice and its average weight is about 0.020 g. Conventional
      pathological slices and oil red O staining confirmed it is mature adipose tissue,
      the fluorescence staining positive confirm them are exogenous. Uninduced group
      newborn tissue are found in the experimental groups of nude mice and its average
      weight is about 0.014 g. Conventional pathological slices and oil red O staining
      confirmed it include some mature adipose tissue, the fluorescence staining
      positive confirm them are exogenous. Two groups of the new wet weight with have
      statistical significance (P < 0.01); gaps in the control group no new
      organization formed. CONCLUSIONS: The cells using enzymatic digestion from human
      liposuction part of the lipid extract are adipose tissue-derived cells. The cells
      can be as seed cells and with solid scaffold of collagen type I it can become fat
      tissue in vivo successfully.

PMID- 19119645
TI  - [Experimental study of electroporation-mediated plasmid gene expression in skin
      and incisional wound].
AB  - OBJECTIVE: To explore the feasibility of electroporation mediated gene transfer
      in rat incisional wound. METHODS: 12 Sprague-Dawley rat's dorsal skins were
      electroporated (800 voltages in amplitude with 6 square wave pulses, each lasting
      20 milliseconds with 200 millisecond interval) after injection of plasmid DNA (1
      microg/microl, in 100 microl PBS) containing enhanced green fluorescence protein
      (EGFP) gene. Electroporated skins were incisionally wounded 24 hours after
      electroporation. Specimens were harvested at day 2, 4, 6, 14, then EGFP
      expression in dermis was observed and quantitatively analyzed with integrated
      optical density (IOD) followed by H&E staining. RESULTS: Electroporation can
      mediate EGFP expression in epidermis, dermis and panniculus muscle. The
      expression level in dermis was the highest at day 2 (IOD = 3.50 +/- 1.45) and
      disappeared at day 14. EGFP expression was not found in dermis if no
      electroporation applied after plasmid injection (IOD = 0). CONCLUSION:
      Electroporation can mediate plasmid gene expression in incisional wound
      efficiently and widely.

PMID- 19119646
TI  - [An algorithm for atrial premature beat classification with abnormal ECG rhythm
      analysis].
AB  - In this paper, an algorithm for atrial premature beat classification with
      abnormal ECG rhythm analysis is presented. The classification algorithm
      identifies QRS morphology by template matching and recognizes abnormal ECG rhythm
      by the features of heart rate and ECG. Algorithm has been evaluated by the MIT
      BIH arrhythmia database and the results show that the specificity and the
      sensitivity for atrial premature beat are 99.5% and 96.9% respectively. atrial
      premature, arrhythmia, beat classification

PMID- 19119647
TI  - [Segmentation of the prostate ultrasound image based on an improved geodesic
      active contour model].
AB  - In this paper, we propose that, the need of the costly re-initialization
      procedure can be completely eliminated by using the variation formulation, thus
      increasing the speed of computing operations. The edge detecting function in the
      geodesic active contour model is improved by incorporating a prior knowledge. The
      accuracy of the segmentation algorithm can be enhanced by using the minimal
      variance. Experimental results show that the proposed algorithm can segment the
      prostate ultrasound images effectively and avoid the problem of contour leakage.

PMID- 19119648
TI  - [A method used in myeloma cell cloning spot image segmentation].
AB  - A new interactive image segmentation method used in the multiple myeloma cloning
      spots image segmentation is presented in the paper. Based on the theory of graph
      cuts, some pixels are selected as the front object and the background seeds, and
      the other parts are treated as the unknown region. Then, an energy function is
      constructed and initialized through K-means, and the minimum cut method is used
      in the segmentation by energy minimization. Last, the image is eroded and
      dilated, and the cloning separate parts could be got effectively. For the pixels
      which may be partitioned wrongly, we use a tool similar to a brush to re-mark the
      front object or the background, and divide once again. Both subjective the
      evaluation criteria and the RUMA, evaluation criteria are used to evaluate the
      method, and the experiment results are satisfactory.

PMID- 19119649
TI  - [Three domains filtering for medical ultrasound images denoising].
AB  - A filtering algorithm is proposed to deal with the medical ultrasonic image
      series in video format, which uses the relativity in spatial domain, gray value
      domain and temporal domain simultaneously. For each frame image, the relativity
      in spatial domain and gray value domain is utilized to construct the adaptive
      neighborhood first. Then the spatial weighted and gray value weighted filtering
      is performed in this neighborhood. Finally, the temporal relativity between the
      adjacent frames is used to perform the temporal weighted filtering. All the
      weighted filtering in the three domains uses Gaussian kernel, thus the filtering
      sensitivity resulting from the threshold selection is reduced, and the stability
      of the algorithm is enhanced. As it can be seen from the experimental results,
      the three-domains filtering algorithm can suppress the noise effectively, and the
      edge details can be reserved well. So it is useful for the feature extraction,
      recognition and analysis.

PMID- 19119650
TI  - [Design of the software system of the platform for long-term blood pressure
      monitoring].
AB  - In this study, a platform for long-term and non-invasive blood pressure
      monitoring is proposed, Its software system and the functions of different
      program modules in the software system are introduced together with the
      development methods of the main modules.

PMID- 19119651
TI  - [IHE ITI-ATNA profile-based solution for the security of regional healthcare
      information sharing].
AB  - In designing and implementing regional healthcare information sharing systems,
      the security problem is a very important issue. According to the Audit Trail and
      Node Authentication (ATNA) Profile of Integrating the Healthcare Enterprise (IHE)
      and the practical experiences in several hospitals in Shanghai, a Proxy/Server
      based security solution for the integration of regional healthcare information
      sharing systems is proposed, which can solve the cross-platform security problems
      of integration, providing some security measures such as Central User
      Authentication, Audit Trail and Node Authentication.

PMID- 19119652
TI  - [Design of the 2D-FFT image reconstruction software based on Matlab].
AB  - This paper presents a Matlab's implementation for 2D-FFT image reconstruction
      algorithm of magnetic resonance imaging, with the universal COM component that
      Windows system can identify. This allows to segregate the 2D-FFT image
      reconstruction algorithm from the business magnetic resonance imaging closed
      system, providing the ability for initial data processing before reconstruction,
      which would be important for improving the image quality, diagnostic value and
      image post-processing.

PMID- 19119653
TI  - [Design and implementation of GpsOne remote heart disease first-aid system].
AB  - This paper introduces how to develop a novel remote heart disease first-aid
      system with N-tier architecture. The system applies GpsOne communication
      technology and professional ECG signal collection technology to the embedded SCM.
      It can provide an accurate location of the patient and his essential ECG details
      for remote heart disease first-aid.

PMID- 19119654
TI  - [Design and implementation of a VB-based virtual operation system for the console
      in an x-ray machine].
AB  - A new experimental software of an X-ray machine's console virtual operation
      system based on VB is introduced. This software can simulate the manual operation
      on the X-ray machine's console, and has the characteristics of easy operation,
      multi-function and good interactivity.

PMID- 19119655
TI  - [Structuralization of digestive endoscopy report based on NLP].
AB  - This paper presents a method based on NLP to realize structuralization of
      digestive endoscopy reports. The method is taking advantage of existing NLP's
      processing technologies and introducing minimal standard terminology (MST) to
      transform a narrative gastroscopy report into the structuralization report based
      on MST, whose accuracy rate is 92.3%.

PMID- 19119656
TI  - [An excel VBA-based electronic marrow testing report].
AB  - This paper introduces an Excel VBA-based method developed for electronic marrow
      testing reports.

PMID- 19119657
TI  - [Dimensional modeling analysis for outpatient payments].
AB  - This paper introduces a data warehouse model for outpatient payments, which is
      designed according to the requirements of the hospital financial management while
      dimensional modeling technique is combined with the analysis on the requirements.
      This data warehouse model can not only improve the accuracy of financial
      management requirements, but also greatly increase the efficiency and quality of
      the hospital management.

PMID- 19119658
TI  - [Design of a lithium-ion battery recharging circuit used in wireless electrical
      stimulation apparatus for urinary incontinence].
AB  - We introduce in this paper a novel design of the lithium-ion battery
      automatically-charging circuit used in portable wireless electronic stimulation
      therapeutic apparatus for urinary incontinence, including its working principles,
      structure and characteristic.

PMID- 19119659
TI  - [Locomotion and control study on autonomous interventional diagnostic micro
      robots].
AB  - This paper introduces the locomotion control and the research status of the
      autonomous interventional diagnostic micro-robots in detail, outlines technical
      problems and difficulties now existing, and discusses the developing trend of
      locomotion control.

PMID- 19119660
TI  - [Development of hip joint simulators].
AB  - Currently, hip replacement is an effective treatment for some hip joint diseases.
      The friction and wear of a prothesis in the human body are the main causes for
      the failure of joint arthroplasty. It is, therefore, very important to simulate
      the working conditions of a hip prosthesis in order to get an optimal design and
      successful clinical applications. This article summarizes wear testing methods of
      hip prostheses and the developing status of their simulators. Three key aspects
      of the simulators, i.e., the structures, motions and lubrications, are analyzed
      in detail. At the end, the developing trend of the simulators are discussed.

PMID- 19119661
TI  - [Finite element analysis and fatigue tests for nitinol vascular stents].
AB  - This essay is to make brief comments on the Nitinol vascular stents fatigue
      lifetime requirements, finite element analysis and fatigue lifetime tests etc.

PMID- 19119662
TI  - [National standard of blood glucose analyzers and common problems found during
      registration tests].
AB  - This article elucidates the understanding of National Standard GB/T19634-2005 "In
      Vitro Diagnostic Test Systems-General Technical Requirements for Blood-Glucose
      Monitoring Systems for Self-Testing" from the perspective of registration tests
      of blood glucose analyzers, and summarizes some of the common problems existing
      in sending the blood glucose analyzers for inspection in registration tests
      according to the relevant regulations.

PMID- 19119663
TI  - [Design of a medical equipment purchasing system].
AB  - This paper introduces the network data dynamic exchange technology applied to the
      design of the medical equipment purchase system according to the process of the
      medical equipment purchasing. The new system adopts B/S structure based on .net
      technology, to realize the medical equipment purchasing information's dynamic
      management of network purchase application and verification, suppliers
      qualification examination and the contact file inquiry etc.

PMID- 19119664
TI  - [Design of a controlling switch set based on RS-232].
AB  - As a common computer keyboard and a mouse can't meet the requirements of some
      special occasions, this paper introduces the design of a controlling switch set
      based on RS-232 for capturing the image at the medical image workstation. Its
      working principles, circuit, assembly together with its associated software
      controller are given in detail. The control switch set features easy
      manufacturing, low cost and a good reliability.

PMID- 19119665
TI  - [Insight into the connotation of minimally invasive tumors surgery for subject
      and promote the development of head and neck surgery].

PMID- 19119666
TI  - [National Minimally Invasive Surgery Symposium on Head and Neck Tumor].

PMID- 19119667
TI  - [Summary of 2008 National Minimally Invasive Surgery Symposium on Head and Neck
      Tumor].

PMID- 19119668
TI  - [Treatment of supraglottic carcinoma with carbon dioxide laser].
AB  - OBJECTIVE: To evaluate the feasibility and curative effects of CO2 laser in
      treatment of supraglottic carcinoma. METHODS: The retrospective analysis included
      32 case of supraglottic carcinoma from February 1995 to June 2005, TNM classified
      as follows: T1N0M0: 20 cases, T1N1M0: 2 cases, T2N0M0: 8 cases and T2N1M0: 2
      cases. The patients were treated with endoscopic laser surgery and selective neck
      dissection (12 cases) or functional neck dissection (4 cases). The follow-up
      period was more than 3 years. RESULTS: Kaplan-Meier survival analysis shows the
      overall 5-year survival rate was 90.6%, and the 5-year survival rate of T1
      lesions and T2 lesions was 95.6% and 78.2%, respectively. The overall 5-year
      local control rate was 96. 8%. The 5-year local-regional control rate was 90.3%.
      With T1 90.9% and T2 89.0% respectively. Two patients had local recurrences, one
      underwent salvage supraglottic horizontal laryngectomy, another one underwent
      total laryngectomy. Two cases with regional recurrences underwent radical neck
      dissection. One of them with concurrent local recurrence was survival after
      salvage operation. Another one with only regional lesion died of recurrence and
      pulmonary metastasis after treatment. Four patients experienced minor
      complications without sequelae. All survival patients had laryngeal preservation
      except the one who received total laryngectomy. CONCLUSIONS: The results of this
      study show that endoscopic CO2 laser surgery is highly effective in the treatment
      of selected supraglottic carcinoma. It shows reliable curative effects and a high
      larynx preservation rate.

PMID- 19119669
TI  - [Treatment of glottic cancer with CO2 laser].
AB  - OBJECTIVE: To discuss the indications, surgical technique and complications of
      CO2 laser in the treatment of glottic cancer. METHODS: Sixty cases of glottic
      cancer (T1 = 52, T2 = 8) operated with CO2 laser between 2003 and 2006 were
      retrospectively analyzed. RESULTS: All patients had remarkable hoarseness after
      the surgery. Their voice improved progressively in the process of the
      postoperative healing. Most of our patients had a near normal voice or only had a
      mild hoarseness in a year. None of our patients had tracheotomy during and after
      the operation. No aspiration occurred as well. Except adhesion of anterior
      commission occurred in two cases of T1b tumors who underwent bilateral vocal
      cords resection, no other complications occurred in this series. Among 60 cases
      of glottic carcinoma, 54 cases were followed up postoperatively from 2 to 5 years
      without recurrence. Four cases had local recurrences. One patient had salvage
      surgery with CO2 laser and was followed up for 2 years without recurrence. Other
      three cases had salvage total laryngectomy. One patient followed up for 2 years
      without recurrence, while another two cases died of recurrence. Two cases were
      lost during the follow up. Three-year and five-year overall survival rate were
      100.0% and 91.5%, respectively. CONCLUSIONS: CO2 laser surgery is a minimally
      invasive, effective and safe procedure for T1 and T2 glottic cancer. Satisfactory
      exposure, good surgical skill and appropriate surgical indication are fundamental
      for the success of treatment.

PMID- 19119670
TI  - [Observation of bridging operation by an autogenous incus in the ossiculoplasty].
AB  - OBJECTIVE: To study the clinical effects of bridging operation by an autogenous
      incus in the ossiculoplasty. METHODS: All the postoperative follow-up data of the
      68 patients were analyzed retrospectively, who underwent bridging operation by an
      autogenous incus in the ossiculoplasty and were followed up for 6-28 months with
      an average of 19.75 months. The autogenous incus which had been reshaped was
      implanted between the intact malleus and the intact mobile stapes. The
      preoperative and postoperative pure tone average (PTA) air-conduction, bone
      conduction and air-bone gap on four frequencies (0.5, 1, 2 and 4 kHz) were
      calculated and analyzed. RESULTS: No postoperative autogenous includes were
      extruded with only two cases displaced. The pure tone air conduction improved
      from a preoperative average of (46.69 +/- 18.32) dB to a postoperative average of
      (30.21 +/- 9.46) dB, while bone conduction improved from a preoperative average
      of (24.72 +/- 10.63) dB to a postoperative average of (18.15 +/- 8.91) dB, as
      well as air-bone gap closed from a preoperative average of 21.97 +/- 10.32 dB to
      a postoperative average of (12.06 +/- 9.46) dB. The success rate (postoperative
      PTA-ABG < or = 20 dB) occurred in 75% of all the cases. The improvement of the
      bone conduction occurred in 66% of all the cases, at least with 10 dB occurred in
      at least two frequencies. CONCLUSIONS: Because of low expenses, high convenience
      in an operation, high stability in effects, very low complications and excellent
      hearing results for the patients, the bridging operation as stated in the above
      was worthy of choice. The autogenous incus could be utilized if the defects
      between the intact, mobile stapes and the intact malleus could be well repaired.

PMID- 19119671
TI  - [Development of the Sino-Nasal Outcome Test-20 Chinese version (SNOT-20 CV)].
AB  - OBJECTIVE: To develop the Sino-Nasal Outcome Test-20 Chinese Version (SNOT-20
      CV). METHODS: By introducing, translating, pretesting, adjusting, and performance
      testing of SNOT-20 inventory, a Chinese draft scale came into being. On the basis
      of the clinical applications and feedbacks from ten domestic hospitals, the scale
      was further modified and was more strictly tested in sixty patients with chronic
      rhinosinusitis, and then its psychometric properties were compared with that of
      the original edition. RESULTS: The SNOT-20 CV showed the following psychometric
      properties: The scale was easily accepted and answered in patients, showing a
      satisfactory feasibility. The split-half reliability, Cronbach' alpha and
      intraclass correlation coefficient were 0.95, 0.88, and 0.98, respectively. The
      content validity was approved by experts of working group. The criteria validity
      calculated between SNOT-20 and SF-36 was -0.67. Factor analysis of construct
      validity showed that the comparative fit index was 0.93 and the 20 items were
      classified into 4 domains which were accorded with the designed constructs. The
      category rating system was of reasonable additivity and comparability. Every
      domain was of sensitivity to effectively discriminate between patient population
      and healthy population (P < 0.01). The standardized response mean of twenty items
      and five important items at three months postoperatively was respectively 0.48
      and 0.57, suggesting moderate responsibility to clinical change. SNOT-20 CV
      passed the tests of feasibility, reliability, validity, scalability, sensitivity,
      and responsibility, showing good properties comparable to that of the original
      edition. CONCLUSIONS: SNOT-20 CV passes the psychometric and clinimetric tests
      and can be used for measuring rhinosinusitis-specific quality of life in China.

PMID- 19119672
TI  - [Effectiveness and related factors of Z-palatopharyngoplasty for treating
      obstructive sleep apnea hypopnea syndrome].
AB  - OBJECTIVE: To investigate the efficacy and related factors of Z
      palatopharyngoplasty for treating severe obstructive sleep apnea hypopnea
      syndrome (OSAHS). METHODS: Thirty four OSAHS patients with graded 1-3 tonsil,
      posterior airway space (PAS) > or = mm , Friedman II and III oropharyngeal airway
      were included in this study, all cases had Z-palatopharyngoplasty. The follow up
      was at least 6 months postoperatively. Measurement parameters of responders and
      nonresponders were analyzed. RESULTS: According to related criterion of China,
      cure rate was 35.3%, accumulative total excellence rate 64.7% and accumulative
      valid rate 70. 6%. The cured and excellence patients were considered as
      responders, the other as nonresponders. The lowest oxygen saturation (LSaO2),
      percentage of time with oxyhemoglobin saturation below 0.90 (CT90), mandibular
      plane angle (MPA), mandibular body length, position of tongue and Friedman
      clinical stage are statistically significant between responder and nonresponder.
      The best cut points of LSaO2, CT90 and MPA were 0.72, 22.80% and 29.40 degrees
      respectively. The logistic regression showed that Friedman stage and MPA entered
      into equation, which was Y = ln [P/(1-P)] = -122.85 + 31.57X1 + 1.01X2, if
      setting X1 as Friedman stage, and X2 as MPA. CONCLUSIONS: Z-palatopharyngoplasty
      is effective surgical approach for OSAHS patients with posterior airway space
      (PAS) > or = 11 mm. The affective factors of Z-palatopharyngoplasty included
      LSaO2, CT90, MPA, mandibular body length, position of tongue and Friedman
      clinical stage. Among them, the mandibular plane angle and Friedman clinical
      stage were predominant factors.

PMID- 19119673
TI  - [Pathological features and clinical managements of nasopharyngeal angiofibroma].
AB  - OBJECTIVE: To study the pathological features of nasopharyngeal angiofibroma (NA)
      and the principles for clinical managements. METHODS: Thirty-five patients with
      NAs were treated in First Affiliated Hospital of Fujian Medical University from
      Oct. 1981 to May 2007. The pathological changes, sites of origin, causes of
      intraoperative bleeding and the experiences of managements were retrospectively
      analysed. Using Fish stage: 6 cases were in stage I, 8 cases were in stage II, 17
      cases were in stage III, 4 cases were stage IV. Two cases via endoscopic surgery,
      2 cases via palatal approach, 19 cases via midfacial degloving approach, 9 cases
      via lateral rhinotomy approach, 3 cases via craniofacial combined approach.
      RESULTS: In nasal cavity and paranasal sinus, the tumor was covered by squamous
      or columnar epithelium. The tumor extensions such as in pterygopalatine fossa and
      infratemporal fossa were covered by fibrous pseudocapsule. All cases of this
      series originated in the lateral wall of posterior portion of the nasal cavity.
      Fifteen of thirty-five cases confidentially originated near sphenopalatine
      foramen. Large and thick vessels in the pedicle region were the exact sites of
      serious intraoperative bleeding. Thirty-one cases were totally removed. Four
      cases were subtotal resected. Visual loss revealed in 6 cases, 4 cases visual
      acuity improved postoperatively. Three cases revealed postoperative dry eye due
      to surgical involvement of the sphenopalatine ganglion. CONCLUSIONS:
      nasopharyngeal angiofibroma is covered by epithelium or pseudo-capsule, it does
      not infiltrate the surrounding tissue. Dissecting along the surface of tumor
      might decrease bleeding and facilitate removal of tumor. An ideal surgical
      management should be done according to actually size and image examination, to
      the greatest extent keeping normal facial appearance. Attention should be paid to
      the complications such as visual loss and dry eye.

PMID- 19119674
TI  - [Intrinsic membrane properties of rat medial vestibular nucleus neurons and their
      responses to simulated vestibular input signals].
AB  - OBJECTIVE: To study the membrane properties of rat medial vestibular nucleus
      (MVN) neurons and their firing responses to simulated input signals of peripheral
      vestibular system, and to discuss how the intrinsic membrane properties
      contribute to physiologic functions in central vestibular system. METHODS: By
      using infrared differential interference contrast technique, whole-cell
      recordings were made from rat MVN neurons under direct observation. On the basis
      of their averaged action potential shapes, the MVN neurons were classified.
      Linear and non-linear currents were put into the neurons to simulate the input
      signals of peripheral vestibular system. The differences of intrinsic membrane
      properties and firing response dynamics were observed between two types. RESULTS:
      The discharge activities were recorded in MVN neurons, which remained in low Ca2+
      high Mg2+ artificial cerebrospinal fluid (ACSF). Neurons are classified as type A
      (33%) characterized by a single deep after-hyperpolarization (AHP) and A-like
      rectification, or type B (63%) characterized by double AHP, and another two
      neurons with all or none of the characters. The passive membrane properties were
      not significantly different between type A and type B neurons, while part of
      active membrane properties was significantly different. Both type A and B neurons
      well responded to simulated current inputs, but disparities existed in response
      range and firing dynamics. CONCLUSIONS: The discharge activities of MVN neurons
      were initiated by their intrinsic membrane properties. Most MVN neurons were
      classified as type A and B, while several showed unrepresentative firing
      properties. Linear and nonlinear inputs evoked a heterogeneous range of firing
      responses. The differences of response range and firing dynamics between neurons
      may determine their different physiological functions.

PMID- 19119676
TI  - [Establishment of the deep cervical lymph node metastasis model of tongue VX2
      carcinoma and observation of its metastatic features].
AB  - OBJECTIVE: To establish the deep cervical lymph node metastasis model of tongue
      VX2 carcinoma in rabbits and to observe its metastatic features. METHODS: The VX2
      carcinomas were transplanted into the left ventral submucosa of tongues of 16
      rabbits by injecting carcinoma mass suspension. According to the time the rabbits
      were killed after the transplantation of VX2 carcinoma, they were divided into
      four groups, or 7-, 14-, 21- and 28-day groups, and 4 rabbits in each group. The
      specimens of transplanted tongue carcinomas and cervical lymph nodes in the
      rabbits were examined histopathologically after they were killed. RESULTS: All
      rabbits developed VX2 tongue carcinomas at the transplanted sites, which were
      confirmed with pathological examination, and the mean diameters of tongue
      carcinomas of 7-, 14-, 21- and 28-day groups were (0.74 +/- 0.06) cm (average +/-
      s), (1.62 +/- 0.06) cm, (1.82 +/- 0.04) cm and (2.52 +/- 0.07) cm respectively.
      No cervical lymph node was palpable at bilateral necks in each rabbit of 7-, 14-
      and 21-day groups, and only 4 rabbits of 28-day group had palpable lymph nodes at
      ipsilateral necks. The histopathological examination revealed no lymph node
      metastasis in the rabbits of 7-day group. Ipsilateral deep cervical lymph node
      metastases were confirmed histopathologically in each rabbit of 14-, 21- and 28
      day groups, which located beside larynx-trachea. Two of 4 rabbits in 28-day group
      occurred bilateral deep cervical lymph node metastases. The mean diameters of the
      ipsilateral deep cervical lymph nodes of 7-, 14-, 21- and 28-day groups were
      (0.52 +/- 0.03) cm, (0.78 +/- 0.04) cm, (0.82 +/- 0.03) cm and (1.42 +/- 0.08) cm
      respectively. No metastasis from the transplanted tongue carcinomas was found in
      superficial cervical lymph nodes and submandibular lymph nodes in all rabbits.
      CONCLUSIONS: The deep cervical lymph node metastasis develops at 2 weeks after
      the transplantation of tongue VX2 carcinoma and a deep cervical lymph node
      metastasis model of tongue VX2 carcinoma can be established.

PMID- 19119675
TI  - [Adenoviral-mediated APE/Ref-1 expression protects rat spiral ganglion cells from
      oxidative damage].
AB  - OBJECTIVE: To address the question if apurinic/apyrimidinic endonuclease/redox
      factor 1 (APE/Ref-1) involved in preventing spiral ganglion cells oxidative
      damage after oxidative stress. METHODS: Primary cultured rat spiral ganglion
      cells were infected with the adenovirus containing APE/Ref-1 for 48 h, then
      treated with H2O2 (0, 10, 25, 50, 100, 300 micromol/L) for 1 h, and finally
      changed back into normal medium. Western blot were used to detect the level of
      APE/Ref-1 protein in the infected cells to ensure APE/Ref-1 over expression as a
      result of adenovirus infection. The cell viability was determined by MTT and the
      apoptosis of spiral ganglion cells was determined by terminal-deoxynucleotidyl
      transferase mediated nick end labeling (TUNEL). RESULTS: Western blot showed that
      infection of adenovirus resulted in APE/Ref-1 over expression in the spiral
      ganglion cells. Over expression of APE/Ref-1 significantly improved cell
      viability in cultures treated with different concentration H2O2 from 50 to 300
      micromol/L However, the apoptosis of cells was significantly inhibited.
      CONCLUSIONS: Over expression of APE/Ref-1 could protect spiral ganglion cells
      from oxidative damage.

PMID- 19119677
TI  - [Clinical efficacy of rapid Rhino Stammberger sinus dressing following endoscopic
      sinus surgery].
AB  - OBJECTIVE: To compare the clinical benefits of rapid Rhino Stammberger sinus
      dressing (RR), a new nasal packing material for functional endoscopic sinus
      surgery (ESS), with traditional packing materials sorbalgon plus Vaseline gauze
      (SV) prospectively. METHODS: Twenty-four patients with chronic sinusitis of the
      similar grade were enrolled in the study. After ESS, the nasal cavities of each
      patient were packed with RR in the right side as observing group and SV in the
      left side as control group. SV in the left nasal cavity was removed in the first
      day after operation and RR remained in the right nasal cavity until the first
      endoscopic follow-up 1 week postoperatively. The same perioperative treatments
      such as irrigation and local steroid were given in both sides of nasal cavities.
      The grade of rhinalgia, nasal obstruction, discharge, bleeding and epiphora in
      each side of nasal cavities were assessed on a visual analogue scale (VAS) by the
      patients at the operation day (packing period), the first day and the second day
      after operation respectively. Postoperative endoscopic assessment of nasal
      cavities including crust, discharge, pseudomembrane, edema of mucosa, bubble and
      ostium obstruction were carried out by a rhinologist on VAS at 1, 2, 3, 4, 6, 8
      weeks postoperatively. The follow-up continued until the complete mucosal
      healing. RESULTS: Three patients were dropped from statistical analysis. One of
      them with severe hypertension bleeding when he awoke from anesthesia, the RR was
      run out from the nasal cavity. The other two were lost in the follow-up. Twenty
      one patients completed the follow -up ranging between 2-20 months. The scores of
      rhinalgia, epiphora at the operation day and the rhinalgia at the first day after
      operation in RR side were lower than SV side (P<0.05). The scores of the amount
      of crust at the first week after operation in RR side were lower than SV side
      (P<0.05). Statistically, no significant deference was found between RR and SV in
      the length of mucosal healing period. CONCLUSIONS: Patients felt more comfortable
      with the package of RR than traditional material. No pain and secondary bleeding
      happened. The efficacy of RR on mucosal healing was similar with SV. RR showed
      some advantages and could be used as packing material following ESS.

PMID- 19119678
TI  - [Three-axis otoconia maneuver treatment in benign paroxysmal positional vertigo].
AB  - OBJECTIVE: To evaluate three-axis otoconia maneuver (TOM) for benign paroxysmal
      positional vertigo (BPPV). METHODS: The data from twenty BPPV patients who
      received three-axis otoconia maneuver treatment and 20 BPPV patients who received
      canalith repositioning (CRP) maneuver treatment were analyzed retrospectively.
      RESULTS: There were 17 patients received 1 TOM session and 3 patients received 2
      TOM sessions while 16 patients received 1 CRP session and 4 patients received 2
      CRP sessions. The chi-square (X2) test was used in evaluating the association
      between two independent samples in a contingency table. Both methods had no
      statistically significant. The significance level for statistical tests was 5%
      (alpha = 0.05). CONCLUSIONS: Three-axis otoconia maneuver could be effective used
      in benign paroxysmal positional vertigo with the advantage of repeatedly
      practicable and instrumental.

PMID- 19119679
TI  - [Diagnosis and treatment of primary hyperparathyroidism complicated with
      hyperparathyroid crisis].

PMID- 19119680
TI  - [Vocal cords aspergillosis: report of 4 cases].

PMID- 19119681
TI  - [Successful treatment of a child with respiratory failure occurred after lime
      inhalation].

PMID- 19119682
TI  - [Anastomosis of the external carotid artery with the internal carotid artery for
      resection of extracranial internal carotid artery aneurysm: report of a case].

PMID- 19119683
TI  - [Congenital middle ear malformation].

PMID- 19119684
TI  - [Transoral laser microsurgery for laryngeal carcinoma].

PMID- 19119685
TI  - Environmental risk factors for heart disease.
AB  - In this review, we discuss current evidence linking environmental pollutants to
      cardiovascular disease (CVD). Extensive evidence indicates that environmental
      factors contribute to CVD risk, incidence, and severity. Migrant studies show
      that changes in the environment could substantially alter CVD risk in a
      genetically stable population. Additionally, CVD risk is affected by changes in
      nutritional and lifestyle choices. Recent studies in the field of environmental
      cardiology suggest that environmental toxins also influence CVD. Exposure to
      tobacco smoke is paradigmatic of such environmental risk and is strongly and
      positively associated with increased cardiovascular morbidity and mortality. In
      animal models of exposure, tobacco smoke induces endothelial dysfunction and
      prothrombotic responses and exacerbates atherogenesis and myocardial ischemic
      injury. Similar mechanism may be engaged by other pollutants or food
      constituents. Several large population-based studies indicate that exposure to
      fine or ultrafine particulate air pollution increases CVD morbidity and
      mortality, and the plausibility of this association is supported by data from
      animal studies. Exposure to other chemicals such as polyaromatic hydrocarbons,
      aldehydes, and metals has also been reported to elevate CVD risk by affecting
      atherogenesis, thrombosis, or blood pressure regulation. Maternal exposure to
      drugs, toxins, and infection has been linked with cardiac birth defects and
      premature CVD in later life. Collectively, the data support the notion that
      chronic environmental stress is an important determinant of CVD risk. Further
      work is required to assess the magnitude of this risk fully and to delineate
      specific mechanisms by which environmental toxins affect CVD.

PMID- 19119686
TI  - Excess winter morbidity and mortality: do housing and socio-economic status have
      an effect?
AB  - OBJECTIVE: To review the published research evidence on the links between excess
      winter mortality (EWM) or excess winter hospitalization (EWH) and housing quality
      or socioeconomic status (SES). DESIGN: Systematic review. CRITERIA: Linked data
      on EWM or EWH and potential associations with housing quality or SES. RESULTS: No
      consistent relations between SES and EWM or EWH. The results for housing quality
      are also inconsistent, with some studies showing a weak protective effect of home
      heating. CONCLUSION: Studies to date do not provide good evidence that housing
      quality or SES factors affect EWM and EWH. More research is needed, particularly
      studies using individual level housing and SES data. Controlled trials of
      interventions would be desirable.

PMID- 19119687
TI  - Dendroremediation of heavy metal polluted soils.
AB  - Heavy metals are among the most common and harmful pollutants reaching the soil
      ecosystem all over the world. Phytoextraction is an effective, non-intrusive,
      inexpensive, aesthetically pleasing, socially accepted, highly promising
      phytotechnology for the remediation of soils polluted with heavy metals. To
      overcome the so-called 'Achilles' heel' of phytoextraction, namely, the long time
      needed for effective remediation, this phytotechnology should be combined with
      other profit-making activities such as forestry or bioenergy production.
      Dendroremediation, or the use of trees to clean up polluted soil and water,
      appears of great potential for metal phytoextraction, especially when using fast
      growing tree species, for example, willows (Salix sp. pl.) and poplars (Populus
      sp. pl.). Most important, the ecologic and environmental risks of dispersing
      heavy metals into the ecosystems by dendroremediation strategies should be
      minimized by selecting the right tree species, properly managing/disposing the
      polluted plant material, or a combination of both options.

PMID- 19119688
TI  - The usage of NHS direct by different ethnic and gender groups in an urban
      population.
AB  - The aim of this study was to determine the level of usage of National Health
      Service Direct (NHSD) by ethnic and gender groups within an urban population. The
      study population comprised all individuals in the City of Preston, Lancashire,
      United Kingdom, who had used NHS Direct between 01 July 2003 and 31 December
      2003. The ethnic and gender composition of this population was compared with that
      of the total population within the study area. The United Kingdom census
      information was analyzed to determine the ethnic composition of the total
      population studied. The expected and actual usage of NHS Direct was determined
      for each section of the population and compared by means of Chi-square analysis
      and the use of standardized residuals. Females from the white ethnic group used
      the service more than expected, whereas females from all ethnic groups combined
      used the service less than predicted. For male callers, Black-African, Indian,
      Pakistani, Bangladeshi, and Asian groups used the service more than expected.
      Particularly high usage was observed in Indian and Pakistani groups. The findings
      of this study show that NHS Direct is being under-used by certain ethnic groups
      and a difference in usage exists depending on gender. As the NHSD is intended to
      be the first port-of-call for healthcare advice, determining why certain groups
      use the service more than others is important. Census data show that the ethnic
      minority communities have grown significantly in recent years. Information is
      lacking, however, on the differences in the usage of healthcare services by
      different ethnic components of the population. A consequence of this situation is
      that certain decisions relating to health care policy cannot be targeted
      effectively. This limitation is important as the Race Relations (Amendment) Act
      2000 places a statutory duty on NHS organizations to promote race equality, in
      policy and service delivery. Our findings also raise questions relating to the
      reliability of some current forms of disease surveillance and also show that NHS
      Direct data to determine patterns of disease, within the population, will be
      biased by the uneven usage of the service.

PMID- 19119689
TI  - [The POISE study].

PMID- 19119690
TI  - [Risk-benefit balance in cardiovascular imaging: the radiation issue].
AB  - Every year 5 billion diagnostic imaging procedures are performed worldwide, and
      about 1 out of 2 tests are cardiovascular examinations. According to recent
      estimates, 30% to 50% of all examinations are partially or totally inappropriate.
      This represents a potential damage in patients undergoing imaging tests (who take
      the acute risks of a stress test procedure and/or a contrast study without a
      commensurable benefit), an exorbitant cost for the society, and an excessive
      delay in the waiting lists for other patients needing the examination. In case of
      ionizing radiation, the reduction of useless imaging tests would improve the
      quality of care also through abatement of the long-term risks related to the dose
      employed. The radiation dose equivalent of common cardiological imaging
      examinations corresponds to about 500, 750 and 1000 chest X-rays for stress
      sestamibi testing, multislice cardiac computed tomography and coronary stenting,
      respectively. Although direct evaluation of the incidence of cancer in patients
      submitted to these procedures is not available, according to the latest 2006
      Biological Effects of Ionizing Radiation Committee VII the estimated risk of
      cancer is about 1 in 750 for a computed tomography scan - higher in women
      (1/500), lower in the elderly (1/1500), and the highest in children (1/100 in
      female children aged <1 year). Such a risk is probably not acceptable when a
      diagnostic procedure is inappropriately applied for mass screening (when the risk
      side of the risk-benefit balance is not considered) or when similar information
      can be obtained by other means. By contrast, it is fully acceptable in
      appropriately selected groups as a filter to more invasive, risky and costly
      procedures.

PMID- 19119691
TI  - [Has high-definition spiral computed tomography changed the management of
      patients with acute pulmonary embolism?].
AB  - Pulmonary embolism (PE) is a common condition carrying a significant degree of
      mortality if not diagnosed early. The diagnosis of PE is challenging, because of
      the non-specific nature of its clinical features. For many years the diagnostic
      strategies for PE have mainly involved ventilation/perfusion lung scan as the
      chief diagnostic procedure, often associated with a few clinical models of pre
      test probability and the D-dimer test. These modalities of diagnosing PE, though
      quite satisfactory in various clinical settings, show several limitations, the
      most important one being the high rate of non-diagnostic procedures. The
      introduction of computed tomography (CT) has changed the diagnostic strategies
      and has become the main diagnostic procedure for diagnosing PE. CT is undergoing
      a rapid technological upgrade, which will open in the near future new frontiers
      in the diagnosis of PE. Nonetheless, CT carries a number of limitations, which
      should be carefully identified. This article reviews the evidences on both the
      traditional and newer diagnostic strategies for PE, outlines their strengths and
      weaknesses and describes future applications of CT for diagnosing PE.

PMID- 19119692
TI  - [Treatment of acute and recurrent pericarditis. What the clinical cardiologist
      should know].
AB  - Pericarditis is a common clinical problem, above all in its incessant and
      recurrent forms. Treatment should be targeted according to etiology, but this is
      often unfeasible with a conventional approach, because most cases are labeled as
      "idiopathic" in the majority of immunocompetent patients from developed
      countries. Clinical risk stratification of acute pericarditis may be useful to
      select patients who should be admitted to hospital, and in whom a complete
      evaluation should be performed to identify causes that require specific therapy.
      In idiopathic and viral pericarditis the mainstay of treatment is the use of
      aspirin or a nonsteroidal anti-inflammatory drug with the possible adjunct of
      colchicine to prevent recurrences, above all in recurrent pericarditis.
      Corticosteroids are too often considered and should be limited to rare, specific
      indications (definite rheumatologic disease, presumed autoimmune etiology,
      intolerance or contraindications to aspirin or non-steroidal anti-inflammatory
      drugs, pregnancy) being a clear risk factor for a prolonged and chronic course of
      the disease in idiopathic or viral forms. Despite the common fear of a possible
      evolution towards constrictive pericarditis, such complication is not recorded in
      acute and recurrent pericarditis of viral and idiopathic etiology. The prognosis
      is good in these cases and the risk of constriction is related to the presence of
      a specific etiology and not to the number of recurrences.

PMID- 19119693
TI  - [Screening for asymptomatic left ventricular systolic dysfunction in high-risk
      patients. Preliminary experience with a program based on the use of ECG and
      natriuretic peptide].
AB  - BACKGROUND: Patients with asymptomatic left ventricular systolic dysfunction
      (ALVSD) have an increased risk of heart failure (HF) and a worse life expectancy.
      Since valuable therapies may prevent such dismal evolution, screening programs
      for ALVSD have recently been advocated to detect as early as possible such
      ominous condition. Echocardiography represents the gold standard for the
      assessment of ALVSD but its indiscriminate use in screening programs is
      impractical. Clinical multivariate risk assessment associated with ECG and serum
      brain natriuretic peptide (BNP) may be a feasible strategy to screen ALVSD. We
      prospectively sought to investigate the feasibility and effectiveness of a
      screening program for ALVSD based on ECG and BNP used in a hierarchical sequence
      in patients at high risk for HF. METHODS: Patients > or =55 years old with > or
      =2 risk factors for HF or > or =70 years old with > or =1 risk factor for HF
      entered the study performing sequentially ECG, BNP and echocardiographic
      evaluation. ALVSD was defined as a left ventricular ejection fraction < or =50%.
      RESULTS: Thirty-three of 122 enrolled patients (27%) had ALVSD. They were older,
      presented more frequently a history of chemotherapy exposure, had often bundle
      branch block and higher BNP levels. No patient without any major abnormalities
      (atrial fibrillation, left ventricular hypertrophy, STT alterations of
      ischemic/strain origin, pathologic Q wave, bundle branch block) on ECG (n=31,
      24.4%) had ALVSD. Among the 91 patients with abnormal ECG, ALVSD was observed in
      33 (36%). The area under the receiver operating characteristic curve to detect
      ALVSD by BNP was 0.86 (confidence interval 0.79-0.94, p<0.0001) and BNP values of
      > or =43 pg/ml showed a sensitivity and a specificity of 94% and 57%,
      respectively. The proposed screening program was able to identify 95% (31/33) of
      patients with ALVSD saving 53% of echocardiographic examinations with a
      substantial reduction of the costs to diagnose ALVSD. CONCLUSIONS: Our
      prospective investigation confirms that ECG and BNP may be useful in detecting
      ALVSD in high-risk patients. A cost-effective screening program based on such
      simple and low-cost diagnostic tests might be employed for the prevention of HF
      in primary and secondary prevention programs in high-risk patients.

PMID- 19119694
TI  - [The "Appropriatezza ECO Milano" project. Assessment of appropriateness of
      indications, prescriptions and clinical utility of two-dimensional Doppler
      echocardiography among inpatients and outpatients of Milan, Italy].
AB  - BACKGROUND: The value of echocardiography in the diagnosis and follow-up of most
      cardiovascular diseases is well established, even though the ever-increasing
      demand for the use of this technique is not always justifiable. The
      "Appropriatezza ECO Milano" project was developed among hospitals in Milan
      (Italy) to foster a rational use of echocardiography. The aim of this study was
      to evaluate and improve appropriateness of requests for two-dimensional color
      Doppler echocardiography, considering indications, prescription behaviors and
      clinical utility in both the outpatient and inpatient settings. METHODS:
      Following several meetings, a consensus was reached whereby a multicenter,
      observational study would be undertaken. We assessed the value of each request in
      agreement with the 2003 American College of Cardiology/American Heart
      Association/American Society of Echocardiography guidelines. An ad hoc Microsoft
      Access database was developed to collect study data, which refer to May 2007.
      Eleven hospitals participated in the study. RESULTS: 4130 echocardiographic
      examinations were considered (2300 performed in men and 1830 performed in women;
      mean age 64 +/- 16 years); 1701 examinations were performed in hospitalized
      patients and 2429 in outpatients. The incidence of pathological findings was
      higher in hospitalized patients (73%) than in outpatients (53%) (Pearson chi2 =
      29, p<0.001). A higher additional clinical value was found in hospitalized vs non
      hospitalized patients (48 vs. 35%, Pearson chi2 = 99; p <0.001). In both
      settings, the majority of echocardiographic examinations were requested by
      cardiologists (inpatients 36%, outpatients 54%). The most appropriate
      examinations were performed more frequently in class I or class IIA hospitalized
      patients (73%) than in outpatients (52%) (Pearson chi2 = 277, p<0.001).
      Furthermore, the least accurate the indication, the less the clinical utility
      found in examinations requested from hospitals and outpatient clinics (64 vs 61%
      in class I patients, Pearson chi2 = 413, p<0.001; 5 vs 11% in class III patients,
      Pearson chi2 = 584, p<0.001). Conclusions. Our data confirm an inadequate level
      of appropriateness of requests for two-dimensional color Doppler examinations in
      either inpatients or outpatients. After over 10 years of passively observing and
      recording this trend, a timely resolution of these issues is topical in order to
      improve the implementation of criteria and to guarantee cost-effective and high
      quality cardiovascular care.

PMID- 19119695
TI  - [Appropriateness in echocardiography. The Italian cardiologist between Dr. Jekyll
      and Mr. Hyde].

PMID- 19119697
TI  - [Comprehensive cardiac computed tomography after acute myocardial infarction].

PMID- 19119696
TI  - [Total anomalous pulmonary venous drainage or what else?].

PMID- 19119698
TI  - On the cover: Castanea.

PMID- 19119699
TI  - Antibiotics for the allergist: part 1.
AB  - OBJECTIVE: To review antibiotic use and selection for disorders commonly seen in
      allergy practice. DATA SOURCES: MEDLINE searches were performed cross-referencing
      the keywords antibiotic, antimicrobial, management, and treatment with multiple
      disorders commonly seen in allergy practice. References of the chosen articles
      were also examined. STUDY SELECTION: Articles were selected based on their
      relevance to the subject matter. RESULTS: A large body of research is available
      that is relevant to both conventional and novel uses of antibiotics. The use of
      antibiotics is in question for some disorders, whereas novel approaches to
      therapy with macrolide antibiotics are areas of active investigation. Meanwhile,
      patterns of microbial resistance continue to evolve. CONCLUSION: For decades,
      antibiotics have been traditional first-line treatments for many disorders.
      Recently, this paradigm appears to be shifting as periods of observation come
      into favor and nonbacterial causes of inflammation are under greater scrutiny.
      Nonetheless, appropriate antibiotic selection often remains a key element in the
      treatment of these disorders. Knowledge of the relevant microbiology is an
      inherent requirement in selecting antibiotic therapies and necessitates awareness
      of current trends in bacterial resistance.

PMID- 19119700
TI  - Probiotics for the treatment of allergic rhinitis and asthma: systematic review
      of randomized controlled trials.
AB  - OBJECTIVE: To evaluate the clinical evidence for the use of probiotics as a
      therapeutic modality for allergic rhinitis (AR) and asthma. DATA SOURCES: PubMed
      was searched to identify randomized controlled trials (RCTs) that studied the
      effects of probiotics on AR (n = 12) and asthma (n = 4). STUDY SELECTION: RCTs
      that studied the effects of probiotics administration on the treatment but not
      the prevention of AR and asthma were selected for inclusion in this review.
      RESULTS: Nine of the 12 RCTs that evaluated clinical outcomes in AR showed an
      improvement due to the use of probiotics. All the RCTs that studied perennial AR
      showed lower symptom scoring and medication use with the use of probiotics
      compared with placebo. Also, 5 of the 8 RCTs that referred to seasonal AR
      suggested an improvement in clinical outcomes. Nine RCTs that reported various
      immunologic measurements of allergy found no significant probiotic effects. The
      RCTs that studied the effect of probiotic administration on the treatment of
      asthma showed no positive effects. CONCLUSIONS: Probiotics may have a beneficial
      effect in AR by reducing symptom severity and medication use. Many more good
      quality studies are needed to resolve this issue.

PMID- 19119701
TI  - Pearls and pitfalls of allergy diagnostic testing: report from the American
      College of Allergy, Asthma and Immunology/American Academy of Allergy, Asthma and
      Immunology Specific IgE Test Task Force.
AB  - The intended purpose of this monograph is to provide a general overview of
      allergy diagnostics for health care professionals who care for patients with
      allergic disease. For a more comprehensive review of allergy diagnostic testing,
      readers can refer to the Allergy Diagnostic Practice Parameters. A key message is
      that a positive allergy test result (skin or blood) indicates only the presence
      of allergen specific IgE (called sensitization). It does not necessarily mean
      clinical allergy (ie, allergic symptoms with exposure). It is important for this
      reason that the allergy evaluation be based on the patient's history and directed
      by a health care professional with sufficient understanding of allergy diagnostic
      testing to use the information obtained from his/her evaluation of the patient to
      determine (1) what allergy diagnostic tests to order, (2) how to interpret the
      allergy diagnostic test results, and (3) how to use the information obtained from
      the allergy evaluation to develop an appropriate therapeutic treatment plan.

PMID- 19119702
TI  - Nasal airway obstruction: allergy and otolaryngology perspectives.
AB  - BACKGROUND: Diagnostic test preferences and management strategies for nasal
      airway obstruction (NAO) may vary depending on medical specialty. OBJECTIVE: To
      discern current attitudes and practices of different medical specialties
      regarding diagnostic and management strategies for patients with NAO. METHODS:
      Cross-sectional survey of all practicing otolaryngologists and medical allergists
      in Wisconsin and parts of northern Illinois (N = 268). Survey participants were
      asked to rank the tests they most commonly perform to differentiate causes of NAO
      and to rank the diagnostic tests they believed were most sensitive and specific
      (criterion standard) for NAO. The second portion of the survey provided 3
      distinct patient scenarios, and participants were surveyed on their treatment
      plans. RESULTS: The survey response rate was approximately 50% for both
      specialties. Nasal endoscopy was the most common diagnostic test for
      otolaryngologists vs allergists (58% vs 2%, P < .001), and allergy testing was
      most commonly used first by allergists (92% vs 0%, P < .001). Nasal endoscopy was
      considered the criterion standard for evaluating NAO by 70% of otolaryngologists
      vs 29% of allergists (P < .001), although nasal endoscopy was ranked in the top 3
      for both specialties without a statistically significant difference. Patient
      scenario responses, however, demonstrated no statistically significant
      differences between the specialties. CONCLUSION: Differences were demonstrated in
      the diagnostic workup preferences and perceptions of the criterion standard for
      NAO between the 2 medical specialties. Specialty bias, practitioner comfort
      level, and patient selection likely accounted for differences in responses.
      However, patient management decisions, medical or surgical, seemed to be similar
      between the specialties.

PMID- 19119703
TI  - Assessing the value of disease management: impact of 2 disease management
      strategies in an underserved asthma population.
AB  - BACKGROUND: The goal of disease management (DM) is to improve health outcomes and
      reduce cost through decreasing health care utilization. Although some studies
      have shown that DM improves asthma outcomes, these interventions have not been
      examined in a large randomized controlled trial. OBJECTIVE: To compare the
      effectiveness of 2 previously successful DM programs with that of traditional
      care. METHODS: Nine hundred two individuals with asthma (429 adults; 473
      children) were randomly assigned to telephonic DM, augmented DM (ADM; DM plus in
      home visits by a respiratory therapist), or traditional care. Data were collected
      at enrollment and at 6 and 12 months. Primary outcomes were time to first asthma
      related event, quality of life (QOL), and rates of asthma-related health care
      utilization. Secondary outcomes included rate of controller medication
      initiation, number of oral corticosteroid bursts, asthma symptom scores, and
      number of school days missed. RESULTS: There were no significant differences
      between groups in time to first asthma-related event or health care utilization.
      Adult participants in the ADM group had greater improvement in QOL (P = .04) and
      a decrease in asthma symptoms (P = .001) compared with other groups. Of children
      not receiving controller medications at enrollment (13%), those in the
      intervention groups were more likely to have controller medications initiated
      than the control group (P = .01). Otherwise, there were no differences in
      outcomes. CONCLUSIONS: Overall, participation in asthma DM did not result in
      significant differences in utilization or clinical outcomes. The only significant
      impact was a higher rate of controllermedication initiation in children and
      improvement in asthma symptoms and QOL in adults who received ADM.

PMID- 19119704
TI  - Relationship of the asthma control test with pulmonary function and exhaled
      nitric oxide.
AB  - BACKGROUND: The Asthma Control Test (ACT) is a short, simple, patient-based tool
      for identifying patients with poorly controlled asthma; however, its value in
      practice has yet to be demonstrated. OBJECTIVE: To clarify the relationship of
      ACT scores and clinical parameters, including pulmonary function tests, peak
      expiratory flow (PEF) indices, and exhaled nitric oxide (eNO) levels. METHODS:
      The study included 105 patients with asthma who underwent routine checkups by
      asthma specialists since September 1, 2006, through January 31, 2007. All
      patients had been taking inhaled corticosteroids with or without other
      medications for asthma for at least 3 months. The patients completed the ACT
      questionnaire and underwent testing for eNO and spirometry. PEF indices,
      including PEF percentage of predicted value (%PEF), lowest PEF during 1 week
      expressed as a percentage of the highest PEF (Min%Max PEF), and PEF variability,
      were also analyzed in patients undergoing PEF monitoring. RESULTS: The ACT scores
      ranged from 8 to 25 (median, 24), and total control was obtained in 45 patients
      (42.8%). The PEF indices and eNO values in the total control group were
      significantly better than those in the less controlled groups. However, the ACT
      scores were weakly correlated with percentage of predicted forced expiratory
      volume in 1 second (r = 0.219), %PEF (r = 0.387), Min%Max PEF (r = 0.354), PEF
      variability (r = -0.351), and eNO values (r = -0.310). Total control of ACT
      included uncontrolled conditions in physiologic and inflammatory parameters.
      CONCLUSION: ACT should be used in combination with pulmonary function tests
      and/or eNO measurements.

PMID- 19119705
TI  - Airflow limitation, asthma, and Chlamydia pneumoniae-specific heat shock protein
      60.
AB  - BACKGROUND: Chlamydia pneumoniae has been associated with asthma. It has also
      been suggested that C pneumoniae infection may lead to lung remodeling in a
      subset of asthmatic patients. Seroreactivity against Chlamydia trachomatis heat
      shock protein 60 (hsp60), a highly conserved, immunoreactive chaperone protein,
      is associated with immunopathologic abnormalities, leading to blinding trachoma
      and tubal infertility. This suggests that the host response to infection may
      affect chronic inflammatory damage to the eye and the fallopian tubes. The
      pathogenesis of C trachomatis disease associations is thought to include
      molecular mimicry (autoimmunity), direct activation of the innate immune response
      via the CD14/toll-like receptor 4 complex, or both. OBJECTIVE: To study whether
      airflow limitation in asthma in C pneumoniae-exposed individuals is associated
      with a specific antibody response to the C pneumoniae hsp60 molecule and not with
      a genus-specific response to the hsp60 molecule. METHODS: In a case-control
      study, we evaluated 138 C pneumoniae-exposed primary care patients (86 adult
      asthmatic cases and 52 nonasthmatic controls) for seroreactivity against a C
      pneumoniae-specific hsp60 fragment and against the C trachomatis hsp60 molecule.
      We analyzed associations with asthma and irreversible lung remodeling as measured
      by means of postbronchodilator forced expiratory volume in 1 second. RESULTS:
      Twenty-seven percent of asthmatic patients were C pneumoniae hsp60 seropositive
      vs 8% of controls (P < .01). Controlling for age, sex, and smoking, C pneumoniae
      hsp60 seropositivity was associated with lower postbronchodilator forced
      expiratory volume in 1 second in asthmatic patients (P < .05). No comparable
      associations were present for C trachomatis hsp60. CONCLUSIONS: In individuals
      with evidence of previous exposure to C pneumoniae infection, a host antibody
      response against a C pneumoniae hsp60 fragment but not against C trachomatis
      hsp60 was associated with airflow limitation in adults with asthma.

PMID- 19119706
TI  - Asthma progression to airway remodeling and bone marrow eosinophil responses in
      genetically distinct strains of mice.
AB  - BACKGROUND: Patient factors that cause long-term airway remodeling are largely
      unidentified. This suggests that genetic differences may determine which
      asthmatic patients develop airway remodeling. A murine model with repeated
      allergen exposure leading to peribronchial fibrosis in complement factor 5 (C5)
      deficient A/J mice has been used to study asthma progression. No studies have
      addressed the systemic effects of allergen sensitization or chronic allergen
      exposure on bone marrow eosinophilopoiesis in this mouse strain. OBJECTIVE: To
      investigate bone marrow eosinophil responses during acute sensitization and
      chronic allergen exposure using genetically distinct mouse strains differing in
      persistent airway reactivity and remodeling. METHODS: The C5-sufficient BALB/c
      and C5-deficient A/J mice were repetitively exposed to intranasal ovalbumin for
      12 weeks. Subsequently, the mice were evaluated for airway eosinophilia, mucus
      containing goblet cells, and peribronchial fibrosis. Both strains of mice were
      also acutely sensitized to ovalbumin. Bone marrow eosinophil progenitor cells and
      mature eosinophils were enumerated. RESULTS: BALB/c and A/J mice have similar
      bone marrow responses after acute allergen exposure, with elevations in bone
      marrow eosinophil progenitor cell and eosinophil numbers. After chronic allergen
      exposure, only C5-deficient A/J mice that developed peribronchial fibrosis
      exhibited bone marrow eosinophilia. BALB/c mice lacked peribronchial fibrosis and
      extinguished accelerated eosinophil production after long-term allergen
      challenge. CONCLUSIONS: Chronic airway remodeling after repeated allergen
      exposure in genetically different mice correlated with differences in long-term
      bone marrow eosinophilopoiesis. Preventing asthma from progressing to chronic
      airway remodeling with fibrosis may involve identifying genetically determined
      influences on bone marrow responses to chronic allergen exposure.

PMID- 19119707
TI  - Predicting an asthma exacerbation in children 2 to 5 years of age.
AB  - BACKGROUND: Asthma exacerbations in young children are prevalent. Identification
      of symptoms or other factors that are precursors of asthma exacerbations would be
      useful for early treatment and prevention. OBJECTIVES: To determine whether diary
      symptoms and beta2-agonist use before an exacerbation could predict an asthma
      exacerbation in children 2 to 5 years of age. METHODS: Post hoc analyses were
      conducted on data collected in a study of 689 patients 2 to 5 years of age with
      asthma symptoms, randomly assigned to montelukast, 4 mg, or placebo daily for 12
      weeks. During the study, 196 patients had an exacerbation. Caregiver-reported
      information (daytime cough, breathing difficulties, limitation of activity,
      nighttime cough or awakening, daytime and nighttime beta2-agonist use) were
      analyzed using general estimating equations with an exchangeable within-subject
      log odds ratio regression structure to identify predictors of an exacerbation.
      RESULTS: Average symptom scores and beta2-agonist use increased significantly
      before exacerbation but at different rates. A combination of daytime cough and
      wheeze and nighttime beta2-agonist use 1 day before the exacerbation was
      identified as strongly predictive of an exacerbation. These methods predicted 149
      (66.8%) of the exacerbations with a very low false-positive rate of 14.2%.
      CONCLUSIONS: No individual symptom was predictive of an imminent asthma
      exacerbation, but a combination of increased daytime cough, daytime wheeze, and
      nighttime beta2-agonist use 1 day before an asthma exacerbation was a strong
      predictor of an exacerbation in children.

PMID- 19119709
TI  - Natural history of food allergy in infants and children in Israel.
AB  - BACKGROUND: Knowledge about the natural history of food allergy, especially
      sesame, is scarce. OBJECTIVE: To follow the natural history of food allergies in
      Israel, particularly of sesame allergy. METHODS: The survey was conducted based
      on clinical records and a detailed questionnaire of children diagnosed as having
      food allergy. RESULTS: We found 234 children with suspected food allergy. Testing
      detected 283 allergies in 180 patients (77%) with confirmed diagnosis. The most
      common allergies were to cow's milk (n = 125), eggs (n = 71), sesame (n = 30),
      and soy (n = 23). Of those with milk allergy, 69% were IgE mediated (group 1) and
      31% were non-IgE mediated (group 2). Group 1 was more likely to have an atopic
      background than was group 2 (P = .003), whereas group 2 was more likely to have
      resolution of the allergy (35 of 39 [90%] in group 2 compared with only 32 of 86
      [37%] in group 1, P < .001). Allergy to soy was found in 23 children, of whom 87%
      manifested with gastrointestinal symptoms and 21 (91%) were also allergic to
      cow's milk. In 19 children (83%), the allergy resolved. Thirty children had
      allergy to sesame, and 73% of them had an atopic background. The allergy resolved
      in only 9 of these patients (30%) at a mean age of 2.8 years. CONCLUSIONS: The
      distribution of food allergens in Israel differs from that in other countries.
      Non-IgE-mediated food allergy and particularly milk and soy allergy were likely
      to resolve completely with time. Sesame allergy was 1 of the most frequent in
      this cohort, was usually IgE mediated, and tended to resolve in only a few
      patients.

PMID- 19119708
TI  - Prescriptions for self-injectable epinephrine and follow-up referral in emergency
      department patients presenting with anaphylaxis.
AB  - BACKGROUND: Anaphylaxis guidelines recommend that patients with a history of
      anaphylactic reaction should carry self-injectable epinephrine and should be
      referred to an allergist. OBJECTIVE: To evaluate how frequently patients
      dismissed from the emergency department after treatment for anaphylaxis received
      a prescription for self-injectable epinephrine or allergist referral. METHODS: A
      retrospective medical record review identified patients with anaphylaxis in a
      community-based study from 1990 through 2000. Records of patients with Hospital
      Adaptation of the International Classification of Diseases, Second Edition or
      International Classification of Diseases, Ninth Revision codes representing
      anaphylaxis were reviewed, and a random sample of patients with associated
      diagnoses was also reviewed. Patients who met the criteria for diagnosis of
      anaphylaxis were included in the study. RESULTS: Among 208 patients identified
      with anaphylaxis, 134 (64.4%) were seen in the emergency department and
      discharged home. On dismissal, 49 patients (36.6%; 95% confidence interval [CI],
      28.4%-44.7%) were prescribed self-injectable epinephrine, and 42 patients (31.3%;
      95% CI, 23.5%-39.2%) were referred to an allergist. Treatment with epinephrine in
      the emergency department (odds ratio, 3.6; 95% CI, 1.6-7.9; P = .001) and insect
      sting as the inciting allergen (odds ratio, 4.0; 95% CI, 1.6-10.5; P = .004) were
      significantly associated with receiving a prescription for self-injectable
      epinephrine. Patient age younger than 18 years was the only factor associated
      with referral to an allergist (P = .007). CONCLUSIONS: Most patients dismissed
      after treatment for anaphylaxis did not receive a self-injectable epinephrine
      prescription or allergist referral. Emergency physicians may be missing an
      important opportunity to ensure prompt treatment of future anaphylactic reactions
      and specialized follow-up care.

PMID- 19119710
TI  - Asthma and obesity.

PMID- 19119711
TI  - Dyspnea and obesity in African American women.

PMID- 19119712
TI  - Mastocytic enterocolitis: a newly described mast cell entity.

PMID- 19119713
TI  - Therapeutic alternatives for chronic urticaria: additional reports on omalizumab.

PMID- 19119714
TI  - What is an effective approach with providers who authorize absences to avoid
      negative responses from malingering employees?

PMID- 19119715
TI  - Underreporting of musculoskeletal disorders among health care workers: research
      needs.
AB  - Extensive evidence suggests that the numbers of workplace injuries and illnesses
      reported annually by the U.S. Department of Labor, Bureau of Labor Statistics,
      are underestimated for all private employers. Several states have passed safe
      patient handling legislation to reduce work-related musculoskeletal disorders
      (WMSDs) among health care workers. Research is needed to improve accurate
      reporting of these types of injuries to allow assessment of the effectiveness of
      this legislation and to enable hospitals and nursing homes to better target
      interventions to areas at high risk for WMSDs. In the interim, occupational
      health nurses and the American Association of Occupational Health Nurses, Inc.,
      can assist in improving the accuracy of occupational surveillance for these work
      related injuries.

PMID- 19119716
TI  - Working through a migraine: addressing the hidden costs of workplace headaches.
AB  - The financial and personal impact of migraines in the workplace is substantial.
      Effective management of workplace migraines includes screening, prevention, and
      effective treatment. Worksite screeners are available to detect the burden of
      undiagnosed migraine in the workplace. Decreasing the personal and financial
      impact of migraines in the workplace requires a variety of strategies predicated
      on collaborative efforts among workers, occupational health nurses, other
      providers, and management.

PMID- 19119717
TI  - Sustaining a healthy work force in the 21st century--a model for collaborating
      through reciprocation.
AB  - Occupational health nurses are positioned to restore and maintain worker health,
      well-being, and safety, thereby increasing productivity. A model of practice is
      needed that provides a comprehensive worker-environment perspective. A model that
      incorporates reciprocation and collaboration increases workers' engagement in
      their own health action plan. It empowers workers and provides a broader
      multidimensional perspective on factors affecting or influencing their health.
      The Reciprocation Model has been designed using the nursing process; it
      incorporates reciprocation and collaboration to assist occupational health nurses
      improve or maintain worker health and safety, as well as achieve corporate goals
      of reducing on-the-job lost time and increasing productivity.

PMID- 19119718
TI  - Part II. Returning to work following bariatric surgery.

PMID- 19119719
TI  - John M. Eisenberg Patient Safety and Quality Awards.

PMID- 19119720
TI  - An interview with Michael Cohen. Interview by David Westfall Bates.

PMID- 19119721
TI  - An interview with Neil Wenger. Interview by Todd Semla.

PMID- 19119722
TI  - The National Coordinating Council for Medication Error Reporting and Prevention:
      promoting patient safety and quality through innovation and leadership.

PMID- 19119723
TI  - Aligning hospital and physician performance incentives: a shared success model.

PMID- 19119724
TI  - Transparency as a pillar of a quality and safety culture: the experience of the
      New York City Health and Hospitals Corporation.

PMID- 19119725
TI  - The CLABs collaborative: a regionwide effort to improve the quality of care in
      hospitals.
AB  - BACKGROUND: Each year, nearly 250,000 cases of central line-associated
      bloodstream infections (CLABs) occur in hospitals in the United States. In 2005,
      the Greater New York Hospital Association and the United Hospital Fund launched a
      collaborative initiative to eliminate CLABs in hospital intensive care units
      (ICUs). COLLABORATIVE DESIGN: Hospital leadership at 36 hospitals committed to
      support their staffs' participation in specific activities, including three
      learning sessions. An infectious disease physician consultant served as an on
      call consultant to provide the necessary clinical guidance, real-time feedback,
      and support. Most hospitals' interdisciplinary CLABs teams met weekly to
      implement evidence-based practices known collectively as the central line bundle,
      determine areas for additional focus, and to reassess strategies using the Plan
      Do-Study-Act (PDSA) model. RESULTS: There was a statistically significant
      decrease of 54% (p < .001) between the mean CLABs rate during the intervention
      period (2.24 infections per 1,000 central line days) compared with the mean
      baseline rate (4.85 infections per 1,000 central line days). By March 2008, the
      rate had dropped by 70% (1.44 infections per 1,000 central line days) compared
      with baseline. At the hospital level, decreases in CLABs rates up to 88% were
      observed between the baseline period and the intervention period, with 56% of
      hospitals achieving at least a 50% decrease in their CLABs rate. The hospitals
      beginning above the national rate decreased their CLABs rates by almost twice as
      much as hospitals that began below the national average. SUMMARY AND CONCLUSIONS:
      Each participating hospital sustained implementation of the central line bundle
      throughout the 33-month intervention, which, along with standardized line
      maintenance procedures, resulted in reduction in, and sometimes elimination of,
      CLABs.

PMID- 19119726
TI  - Focusing measures for performance-based privileging of physicians on improvement.
AB  - BACKGROUND: The Joint Commission requires ongoing professional practice
      evaluation--or what Cincinnati Children's Medical Center (CCHMC) has termed
      performance-based privileging (PBP)--for the medical staff reappointment and
      reprivileging process. BUILDING A SYSTEM: CCHMC is a 475-bed academic medical
      center affiliated with the University of Cincinnati College of Medicine. Medical
      staff members are reappointed every two years, with divisions having staggered
      reappointment dates throughout the two-year cycle. In 2004, CCHMC devised a model
      in which the 38 divisions retained responsibility for development of measures;
      collection, maintenance, display, and monitoring of individual provider
      performance data; and sharing of data with providers, while medical staff
      services retained responsibility for ensuring compliance with timelines,
      technical assistance related to measure development, and the collection and
      display of data. Each clinical division developed a preliminary list of measures.
      The original PBP process was tested in 2005 and has been revised several times in
      response to division feedback. DISCUSSION: Members of all 38 clinical divisions
      have now been reappointed to the medical staff at least twice using measures that
      have become more robust, meaningful, and outcome oriented. Many measures support
      organizational or divisional quality imoprovement aims, are evidence based, or
      build on initiatives sponsored by external bodies and specialty societies.
      Examples of measures are shared via the PBP intranet, personal consultations, and
      an annual provider performance improvement conference. Yet, challenges remain,
      such as the absence of real-time, provider-specific, risk-adjusted data and the
      difficulty of attributing provider-specific outcomes when most complex and high
      risk care is managed by a team.

PMID- 19119727
TI  - Medication errors involving patient-controlled analgesia.

PMID- 19119728
TI  - Using an advanced practice nursing model for a rapid response team.
AB  - Outcomes, including reductions in codes per 1,000 discharges, failure-to-rescue
      rates, and medical-surgical mortalities and improvement in staff satisfaction,
      were all indicative of the efficacy of the APN-model RRT. Future studies might
      compare these outcomes with those of other team models.

PMID- 19119729
TI  - Learn more about mental health care.

PMID- 19119730
TI  - Early discharge fuels A&E visits.

PMID- 19119731
TI  - The right place to die.

PMID- 19119732
TI  - Act now, save later.

PMID- 19119733
TI  - One chance to get it right.

PMID- 19119734
TI  - Championing dignity.

PMID- 19119735
TI  - Don't quote me.

PMID- 19119736
TI  - A whole-systems approach for dementia care.

PMID- 19119737
TI  - Bakewell can't shake off 'crumpet' epithet.

PMID- 19119738
TI  - Nurses' perceptions of care received by older people with mental health issues in
      an acute hospital environment.
AB  - A qualitative methodology using focus groups was used to access the views of 14
      nurses in one NHS trust about caring for older people with mental health issues
      in an acute hospital setting. The findings suggest that communication about
      mental health disorders between healthcare professionals and with patients and
      relatives in the acute general hospital setting needs to be improved and that
      assessment throughout the care pathway is often inadequate.

PMID- 19119739
TI  - Introducing a post-fall assessment algorithm into a community rehabilitation
      hospital for older adults.
AB  - The aim of this paper is to describe a study designed to standardise and improve
      practice by introducing a new assessment tool to guide nurses in the evaluation
      of patients following a fall in a community hospital for older people. The idea
      behind the assessment tool is that it would support nurses in prioritising
      medical attendance to review particular patients by requesting immediate, same
      day or the next working day care. An action research approach was used.

PMID- 19119740
TI  - Think positive.

PMID- 19119741
TI  - Now and then: nurse, I want my daddy.

PMID- 19119742
TI  - Working with young people.

PMID- 19119743
TI  - Use of single rooms on the children's ward: Part 1.
AB  - Most general children's wards have a limited number of single occupancy rooms.
      This poses problems when a child presents at hospital needing a single room when
      one is not available. In this first of a two-part article we present the findings
      of a literature review, beginning with an exploration of the psychological and
      social impact of isolation nursing. Evidence for the use of single rooms in
      infection control and to meet the psychosocial needs and personal preferences of
      children and families is then discussed. The literature supports the use of
      single rooms in infection control but also offers alternatives such as cohort
      nursing. In relation to psychosocial needs and family preferences the literature
      suggests that while there is an argument for ensuring privacy in certain
      circumstances, this needs to be balanced against the detrimental psychological
      effects of isolation. Part two in the February 2009 issue presents guidance for
      practice on the use of single rooms based on this review.

PMID- 19119744
TI  - Measuring hospice services.

PMID- 19119745
TI  - Factors influencing pain management in children.
AB  - AIM: To identify factors that influence nurses' pain management in children.
      METHOD: A qualitative design was used. Twenty-one nurses working in one
      paediatric department were interviewed using semi-structured interviews. Data
      were analysed by means of content analysis. FINDINGS: The way nurses manage pain
      in children is affected by factors such as co-operation between nurses and
      physicians and between nurses and patients, children's behaviour, routines in the
      organisation, and the experience and knowledge of nurses. CONCLUSION: Pain
      management in children could be improved through increased co-operation between
      nurses, physicians and parents. Planning time and good routines could facilitate
      pain management. Education about pain management and children's pain behaviour
      might also improve nurses' ability to manage pain in children.

PMID- 19119746
TI  - Eczema and allergy: how useful is allergy testing?
AB  - AIM: To determine the value of allergy testing using skin prick tests and
      specific immunoglobulin E measurements (spIgE) to identify allergies in children
      with eczema (atopic dermatitis) and to correlate these findings with the clinical
      history METHOD: This was a retrospective study of 100 children with moderate to
      severe eczema attending hospital for treatment. In each child a detailed clinical
      history of allergy was documented and the severity of atopic dermatitis assessed
      by the research nurse. Skin prick tests were carried out using grass pollen,
      house-dust mite and egg-white allergens. Blood tests were taken for total IgE and
      spIgE responses to these allergens. A control group of 100 children with no
      history of allergy was also included for comparison. RESULTS: More than two
      thirds of the children (68 per cent) had a high total IgE (> 1000 kU/l). SpIgE
      tests to grass and house-dust mite were shown as the most frequent finding
      although statistically poor in association with the clinical history. Allergy to
      these airborne allergens was found to be more common in the older age group of
      children. whereas egg-white allergy was seen more commonly in the younger age
      group. CONCLUSION: There is no one diagnostic test for allergy in children with
      atopic dermatitis. The results of these tests in combination with the clinical
      history provide a more accurate assessment of the child's allergy status.
      Children with moderate to severe eczema have a high incidence of associated
      allergy. Skin prick tests and spIgE proved helpful but neither was exclusively
      better than the other for diagnosis. The clinical nurse specialist is able to
      make a valuable contribution to the family through offering support and carrying
      out allergy tests.

PMID- 19119747
TI  - Resilience and coping strategies in adolescents.
AB  - Resilience has gained considerable attention over the past four decades since
      researchers observed that children and youth could cope and adapt in spite of
      adversity. Adolescence is considered to be a period of vulnerability for most
      individuals as they often partake in risky behaviour. Using multiple databases
      and inclusion criteria, a review of the literature was undertaken to determine
      what is known about this concept in reported studies from 2000-2008. Empirical
      evidence indicates that resilience is dynamic, developmental in nature, and
      interactive with one's environment. A variety of variables have been studied to
      clarify the concept of resilience in adolescents. Although there is an abundance
      of literature on adolescent resilience, little is known about this process in the
      healthy, well-adjusted adolescent. There are gaps and inconsistencies in reported
      findings. Results of the review provide useful resources for application to
      nursing education, practice, and research Research resources and instruments
      measuring resilience provide additional knowledge. Nurses are in a key position
      to help the adolescent minimise risky behaviors and promote positive lifestyle
      practices.

PMID- 19119748
TI  - Intestinal failure and long-term parenteral nutrition in children.
AB  - Infants and children with intestinal failure such as that seen in short bowel
      syndrome will require parenteral feeding, some of them in the long-term.
      Complications of long-term feeding include those associated with central venous
      catheter use and liver failure associated with parenteral nutrition. Careful
      monitoring and supportive care from experts in the paediatric nutrition support
      team are required to ensure that the risks of parenteral nutrition are minimised.

PMID- 19119749
TI  - What have we done for you lately? Time to tackle health insurance costs?

PMID- 19119750
TI  - (Premature) death and taxes.

PMID- 19119751
TI  - Patient non-compliance the real error.

PMID- 19119752
TI  - Recovery audit contractors. A look at Medicare's latest tool for recouping
      improper payments.

PMID- 19119753
TI  - Report card for your practice.

PMID- 19119754
TI  - Adolescent and adult asthma: guidelines for stepwise treatment.

PMID- 19119755
TI  - Meet our members Richard G. Pellegrino, MD, PhD.

PMID- 19119756
TI  - Lead outreach needs for the State of Arkansas.
AB  - More than 300, 000 American children remain at risk for lead exposure. Many
      Arkansans live in poverty and old, rented dwellings, which can lead to or
      exacerbate effects of lead exposure. Arkansas has, however, had minimal lead
      surveillance, awareness, outreach, or abatement programs in recent years. This
      article presents new information on lead exposure to empower practitioners and
      concerned parties in Arkansas to initiate lead-poisoning prevention.

PMID- 19119757
TI  - Research ethics consultation: the Stanford experience.

PMID- 19119758
TI  - Oncology consent forms: failure to disclose off-site treatment availability.

PMID- 19119759
TI  - The antidepressant debate and ethically defensible placebo-controlled trials.

PMID- 19119760
TI  - Taking steps to protect patients from specimen-handling errors.

PMID- 19119761
TI  - Intraop MRI in a community hospital.

PMID- 19119762
TI  - O-scanner: real-time imaging in the OR.

PMID- 19119763
TI  - Keeping it low: protecting teams from radiation during surgery.

PMID- 19119765
TI  - Managing an endomechanical conversion.

PMID- 19119764
TI  - Minnesota's retained object protocol.

PMID- 19119766
TI  - Full rotation three-dimensional intraoperative imaging during spinal surgery (O
      arm Imaging System).

PMID- 19119767
TI  - A mighty weapon: steam sterilization.

PMID- 19119768
TI  - OR leaders converge on Washington, DC.

PMID- 19119769
TI  - Medicare issues long-awaited ASC CfCs.

PMID- 19119770
TI  - ASC payment plan updated for 2009.

PMID- 19119771
TI  - Keep IMS Task Force Report handy during health care reform discussions.

PMID- 19119772
TI  - Medicare advantage plans--regulatory quirks.

PMID- 19119773
TI  - Your IMS guide to making a difference.

PMID- 19119774
TI  - The medical home model of care.

PMID- 19119775
TI  - A full agenda for all of us.

PMID- 19119776
TI  - Consider the ironman investment strategy.

PMID- 19119777
TI  - [Ombudsman of private and nursing insurance].

PMID- 19119778
TI  - [Burnout--a new disease?].
AB  - Since Herbert Freudenbergers "Staff Burnout", published in 1974, burnout has
      become a synonym for psychosomatic, psychological symptoms and social
      consequences of a long-lasting workload exceeding an individual's capacity.
      Without any binding definition, the term burnout is used by patients as well as
      their doctors and therapists as a medical diagnosis. Described by Freudenberger
      from a patient's point of view, the term tries to integrate symptoms (fatigue,
      emotional exhaustion, reduced personal accomplishment and distancing from
      clients) as well as cause (job strain) of the burnout process. Thus burnout was
      claimed to have nothing in common with psychiatric disorders. Altogether this
      burnout concept is fairly plausible and attractive for people suffering from the
      symptoms. It also lowers the threshold to think about work related and
      psychosomatic problems and to look for therapeutic support. According to the
      criteria of modern diagnostic systems like DSM-IV and ICD-10, the attempt to
      integrate symptoms and causes of a psychosomatic phenomenon in a diagnosis will
      fail. In ICD-10 burnout only can be found as an--undefined--additional diagnostic
      term. Scientific data show that people suffering from burnout are a quite
      heterogeneous group, including people who had once been highly motivated and
      successful in their business as well as people feeling overworked all their
      lives. While burnout is not convincing as a diagnostic term, its high popularity
      highlights the fundamental needs and problems of a changing society,
      characterised by increasing work related stressors and decreasing social
      security.

PMID- 19119779
TI  - [Treatment options for cartilage damage in the knee joint (II)].

PMID- 19119780
TI  - [Discussing a "two-tiered medical system": a statement].
AB  - The criticism of a "two-tiered medical system" is a political slogan, which is
      also not exactly defined. However, for the public discussion this is not of
      further importance because talking about a "two-tiered medical system" has a
      priori a negative impact; in particular in times when people's fears surrounding
      medical care in Germany are great. Especially in a public health insurance
      system, insured people worry that in the future they will only receive the most
      essential medical services, rather than all services that are deemed reasonable
      and medically appropriate. One of the central themes in the discussion of a "two
      tiered medical system" that causes disputes (or animosity) between privately and
      publicly insured persons arises when comparing differences in waiting periods to
      see a doctor and additional medical treatments made available to the privately
      insured. Critics of the "two-tiered medical system" envision a "one-tiered
      medical system"; one in which every person receives uniform healthcare, and in
      which the "purchase" of additional medical treatments is not permitted. However,
      the "one-tiered medical system" remains a theoretical construct. Service
      differences based on price differences are the reality. So the problem of the
      "two-tiered medical system" manifests itself only when those services that go
      beyond the basic care (privately offered services) negatively impact basic care,
      and/or displace basic care offerings. An example of this would be when a publicly
      insured patient has to wait longer to see a doctor because preference is given to
      privately insured patients. Economically speaking, negative external effects come
      into play. This causality has not been found or proven to be present in the
      German healthcare system. It exists neither in the inpatient nor in the
      outpatient healthcare sector. There is no basis to the claim that there is a
      difference in treatment favouring private patients with detrimental effects to
      non-privately insured patients. Therefore the claim that a "two tiered medical
      system" exists is negated. On the contrary: In the German health care system
      treatment differences above and beyond the basic services lead to an advantage
      for publicly insured patients. There are no negative, but rather positive
      external effects. This is mainly attributed to the increased doctors' revenue in
      the outpatient sector which amounted to Euro 4.4 billion in 2006 alone.
      Therefore, private patients subsidise the public insurance by funding a
      disproportionately high share of doctors' budgets.

PMID- 19119781
TI  - [Congress of alternative practitioners: propagating of questionable methods].

PMID- 19119782
TI  - [Anxiety and risk--political and insurance medicine assessment].

PMID- 19119783
TI  - [Electromagnetic blood diagnosis--treatment with nosodes, organ preparations and
      colonic hydrotherapy].

PMID- 19119784
TI  - [Predicting liver fibrosis with non-invasive tests--a hope for the future].

PMID- 19119785
TI  - [Utility of various non-invasive methods for fibrosis prediction among Basque
      Country patients with phenotypic hemochromatosis].
AB  - OBJECTIVE: To determine whether the product of multiplying age by liver iron
      concentration (LIC) (fibrosis index; cut-off, 480,000), platelets, transaminases,
      and ferritin values are related to the risk of high grade fibrosis. METHODS: A
      retrospective study of 32 patients with hereditary hemochromatosis (HH) with
      phenotypic expression. All patients had a liver biopsy with LIC. RESULTS: In 7
      patients a magnetic resonance imaging (MRI) scan (1.5 T) was obtained with LIC
      following Alustiza's protocol. Liver biopsy: fibrosis grade (F) 0-2 in 23
      patients; F 3-4 in 9. Fibrosis index (FI) showed a specificity of 68%,
      sensitivity of 85.7%, positive predictive value (PPV) of 42.8%, and negative
      predictive value (NPV) of 94.4% for high-grade fibrosis. Platelet count ( <
      200,000) revealed a NPV of 94.7% for F3-4. Aspartate transaminase (AST) levels
      above the upper limit of normal showed a NPV of 94.4%; ferritin levels (> 1,000)
      a NPV of 75%, and MRI-derived LIC x age (> 480,000) a NPV of 80%. The combination
      of FI (either by biopsy or MRI) with transaminases, and of platelets with
      transaminases revealed a NPV of 100%. CONCLUSIONS: FI > 480,000 and platelets <
      200,000 have the highest sensitivity for high-degree fibrosis prediction. A
      negative result allows to discard significant fibrosis in 94% of cases. MRI
      allows a good fibrosis prediction.

PMID- 19119786
TI  - [Morphologic changes in the proximal jejunum after partial hepatectomy in rats].
AB  - INTRODUCTION: Partial hepatectomy is being used with increasing frequency and
      wider surgical indications including living donor transplantation, particularly
      in children. Our aim was to study the morphologic changes that occur in the
      proximal jejunum as a result of the anatomic, functional, and metabolic unity of
      the liver and small intestine. MATERIAL AND METHODS: Twenty-four Wistar rats were
      divided into 2 groups, a control group and an experimental group (30, 90, and 180
      days). Changes in the proximal jejunum after 70% partial liver resection were
      studied by evaluating 4 parameters (total wall width, villous height, crypt
      depth, and villous thickness). RESULTS: Jejunal total wall width increased
      significantly in the experimental group (p < 0.001). Villous height increased
      significantly in the experimental group as compared to the control group (p <
      0.001). Villous thickness increased, and crypt depth decreased in the
      experimental group, but these changes were not statistically significant.
      CONCLUSIONS: Partial hepatectomy (70%) originated trophic changes in the proximal
      jejunum that persisted in the short and long term, giving rise to parietal and
      villous hypertrophy.

PMID- 19119787
TI  - [Evaluation of the endoscopic response to argon plasma coagulation in patients
      with chronic radiation proctopathy].
AB  - OBJECTIVES: To evaluate endoscopic improvement after argon plasma coagulation
      (APC) in symptomatic patients with chronic radiation proctopathy. METHODS AND
      PATIENTS: A prospective study of 38 patients with radiation proctitis (26 males
      and 12 females, mean age 70.9 +/- 7.38 yrs), and with rectal bleeding and or
      anemia. We performed monthly interviews, blood tests, and APC sessions until
      rectal bleeding had ceased and hemoglobin and ferritin levels were improved, with
      a follow-up of 24 months. We used blood testing, bleeding scores (Chutckhan's
      index), and endoscopic scores to evaluate improvement. RESULTS: Mean time between
      inclusion and follow-up completion was 28.5 +/- 3.9 months. Mean number of
      sessions per patient was 3.6 +/- 2.7. There was a significant decrease (2.29 +/-
      1.8 vs. 0.59 +/- 1.12, p < 0.05) in rectal bleeding (Chutckan score) from
      baseline after APC. There was a significant increase in hemoglobin levels (11.3
      +/- 3.05 vs. 14.014 +/- 1.29, p < 0.001) and ferritin levels (31.15 +/- 66.45 vs.
      80.60 +/- 55.6, p < 0.05) from baseline after APC. Also, there was improvement in
      the endoscopic index at the end of treatment, as well as in friability (p <
      0.0001) and involved surface area (p < 0.0001). CONCLUSION: Argon plasma
      coagulation is an effective technique, and the endoscopic index is a useful tool
      to evaluate endoscopic improvement.

PMID- 19119788
TI  - [Hepatocellular carcinoma in the elderly: clinical characteristics, survival
      analysis, and prognostic indicators in a cohort of Spanish patients older than 75
      years].
AB  - AIMS: Hepatocellular carcinoma (HCC) remains poorly characterized in elderly
      patients with comorbid conditions, a fact that limits the clinical management of
      the disease. This study analyzes the natural history of HCC in patients older
      than 75, and determines factors that condition their survival. PATIENTS AND
      METHODS: A retrospective analysis of 235 patients with HCC divided into 2 groups
      by age at diagnosis: < or = 75 (n = 186) and > 75 (n = 49). After comparing their
      clinical variables (chi2 and t test), a logistic regression analysis was
      performed to determine factors associated with receiving locoregional treatment
      (versus symptomatic treatment). Survival in the 2 groups was compared using a log
      rank test with subsequent multivariate analysis (Cox proportional hazards model).
      RESULTS: There were no differences between groups for sex, presence of cirrhosis,
      etiology, Child-Pugh score, BCLCancer stage, presence of ascites or portal
      thrombosis, or bilirubin, AST, ALT, gammaGT, LDH or hematocrit values. Patients
      of advanced age were more frequently diagnosed in the presence of clinical
      manifestations, and had multifocal, non-localized disease and alpha-fetoprotein
      levels > 400 ng/mL (all p < 0.05). This group received exclusively symptomatic
      treatment in 78% of cases (compared to 33% in younger patients), and only 3 of
      them underwent surgical resection (p < 0.0001). Age older than 75 was a
      predictive factor for not receiving locoregional therapy (p < 0.0001). Survival
      in the elderly group (9.8 +/- 1 months) differed substantially from that of
      younger patients (25.6 +/- 2 months) (p < .00001). Advanced age continued to be a
      prognostic factor of poor survival in the multivariate analysis (p = 0.025), but
      lost significance when the analysis was stratified by treatment subgroups (p =
      0.344). CONCLUSIONS: The lower survival seen in elderly patients with HCC, beyond
      differences in tumor extension or liver failure, seems conditioned by the use of
      suboptimal treatment in this population.

PMID- 19119789
TI  - [Large balloon dilation for removal of bile duct stones].
AB  - AIM: To assess the efficacy and safety of dilatation of the papilla of Vater with
      large balloons for the treatment of choledocolithiasis in patients with difficult
      or risky extraction due to stone characteristics or peripapillary anatomy.
      DESIGN: Prospective. PATIENTS: This study includes 93 patients in whom large
      balloon dilation was performed between June 2005 and January 2008. Patients had
      multiple large stones, tapered distal CBD (common bile duct), peri-/intra
      diverticular papilla, and previous sphincterotomy or Billroth-II surgery. A
      controlled radial expansion (CRE) balloon with a diameter range of 12-20 mm was
      used. RESULTS: Stone removal was achieved in a single session in all patients
      (100 %). Most procedures (86%) did not require an extended exploration time.
      Mechanical lithotripsy was needed in 3.2 % of cases. There were two mild
      complications (2.1%). Hyperamilasemia was detected in 16% of patients.
      CONCLUSIONS: Papillary dilation with a large balloon is an effective, safe, and
      easy technique for the retrieval of difficult common bile-duct stones. The
      procedure neither adds time to the exploration, nor increases complications, and
      obviates the need for mechanical lithotripsy in a majority of patients.

PMID- 19119790
TI  - [Update on the management of hepatic encephalopathy].

PMID- 19119791
TI  - [A large hematoma in the abdominal wall after trocar insertion].

PMID- 19119792
TI  - [A rectal ulcer perforated into the presacral space].

PMID- 19119794
TI  - [Autoimmune pancreatitis: inflammatory pseudotumor, multifocal fibrosclerosis,
      portal hypertension, and long-term outcome].
AB  - Autoimmune pancreatitis is a recently characterized disease that still
      constitutes a diagnostic challenge, especially regarding differential diagnosis
      from neoplasia. Long-term outcome is poorly known. We herein report a case of a
      patient with autoimmune pancreatitis and 14 years of follow-up, and show its
      clinical, biochemical, and morphological characteristics. A 54-year-old female
      presented with obstructive jaundice and abdominal tenderness, as well as a mass
      at the pancreatic head on a CT scan, suggestive of pancreatic neoplasia. Surgery
      showed an increase of the whole pancreas, malignancy was intraoperatively ruled
      out, and a cholecystectomy and choledochoduodenostomy were carried out. The
      diagnosis was chronic pancreatitis. Over the following years different autoimmune
      complications developed, including asthma, salivary gland swelling, and
      sclerosing cholangitis, as well as recurrent episodes of jaundice, and exocrine
      and endocrine pancreatic failure. The development of these complications combined
      with the demonstration of high serum levels of IgG4 and carbonic anhydrase II led
      to a re-evaluation of the initial histology of the pancreas, leading to a final
      diagnosis of autoimmune pancreatitis: IgG4+ lymphoplasmacytic infiltrates,
      fibrosis, and obliterative phlebitis. New complications developed during the last
      few years: retroperitoneal fibrosis with portal hypertension, esophageal varices,
      and splenomegaly.

PMID- 19119793
TI  - [Autoimmune pancreatitis associated with retroperitoneal fibrosis: outcome after
      24 months of follow-up].
AB  - INTRODUCTION: Autoimmune pancreatitis is a kind of chronic pancreatitis
      characterized by the presence of lymphoplasmacytic infiltration and severely
      elevated serum IgG and IgG4, which has been associated to many extrapancreatic
      lesions and other autoimmune disorders, leading to the theory of an autoimmune
      mechanism involved in the pathogenesis of this disease. CASE REPORT: We report
      the case of a man who simultaneously presented with autoimmune pancreatitis
      associated with retroperitonal fibrosis, and a lesion of the extrapancreatic bile
      duct, with total response to corticosteroid treatment for 4 months and absence of
      recurrence after 24 months of follow-up. DISCUSSION: Autoimmune pancreatitis is a
      kind of chronic pancreatitis that is probably a part of a systemic autoimmune
      disease, with retroperitoneal fibrosis and extrapancreatic bile duct lesion being
      the most commonly associated extrapancreatic lesions. A correct diagnosis and
      early treatment of this disease may aid in the total resolution of lesions,
      especially in cases with a low activity grade.

PMID- 19119795
TI  - [Glomus tumor in the gastric antrum].

PMID- 19119796
TI  - [ERCP and plain abdominal radiology].

PMID- 19119798
TI  - [Uncommon colonic polypoid lesion].

PMID- 19119797
TI  - [Hepatic angiomyolipoma: a challenging preoperative diagnosis].

PMID- 19119799
TI  - Multiple gastric carcinoid tumors.

PMID- 19119800
TI  - Obscure gastrointestinal bleeding due to ileal carcinoid tumor diagnosed by
      capsule endoscopy.

PMID- 19119801
TI  - Phase behavior of hyperbranched polymer systems: experiments and application of
      the perturbed-chain polar SAFT equation of state.
AB  - Vapor-liquid equilibrium data for systems of hyperbranched polymer (HBP) and
      carbon dioxide are reported for temperatures of 285-455 K and pressures up to 13
      MPa. The bubble-point pressures of (CO2 + hyperbranched polyester) and of (CO2 +
      hyperbranched polyglycerol + CH3OH) samples with fixed compositions were measured
      using a Cailletet apparatus. The system (CO2 + polyglycerol + CH3OH) also
      exhibits a liquid-liquid phase split characterized by lower critical solution
      temperatures. For this system cloud point curves and vapor-liquid-liquid bubble
      point curves were also measured. Moreover, a thermodynamic model has been
      developed for HBP mixtures in the framework of the perturbed-chain polar
      statistical association fluid theory (PCP-SAFT) equation of state accounting for
      branching effects. There is no additional binary interaction parameter introduced
      along with the branching contributions to the model. Although the miscibility gap
      in the system (CO2 + polyglycerol + CH3OH) is not predicted by the model, PCP
      SAFT including branching effects gives a good representation of the bubble-point
      curves of this system at temperatures lower than the lower solution temperature
      (LST).

PMID- 19119802
TI  - A study on the formation and thermal stability of 11-MUA SAMs on Au(111)/mica and
      on polycrystalline gold foils.
AB  - In this article we present a comprehensive study of 11-mercaptoundecanoic acid
      self-assembled monolayer (SAM) formation on gold surfaces. The SAMs were prepared
      in ethanolic solution, utilizing two different substrates: Au(111)/mica and
      polycrystalline gold foils. Several experimental methods (X-ray photoelectron
      spectroscopy, Fourier transform infrared spectroscopy, and atomic force
      microscopy) reveal a well-defined SAM. The main focus of this work, however, was
      to test the stability of these SAMs by thermal desorption spectroscopy. The
      spectra show different desorption peaks indicating different adsorption states
      and/or decomposition products on the surface. The assumed monolayer peak, which
      can be attributed to desorption of the intact molecule, is detected at 550 K.
      Further desorption peaks can be found, which result, e.g., from cracking of the S
      C bond on the surface, depending on the substrate quality and on the residence
      time under ambient conditions.

PMID- 19119803
TI  - Laparoscopic versus open simple prostatectomy: an evaluation of morbidity.
AB  - PURPOSE: To evaluate the morbidity between laparoscopic simple prostatectomy
      (LSP) and open simple prostatectomy (OSP) in the management of benign prostatic
      hyperplasia. PATIENTS AND METHODS: From January 2003 through January 2008, 280
      consecutive patients underwent adenomectomy either by an extraperitoneal
      laparoscopic transcapsular "Millin" approach (96 patients, 34.3%) or open
      transvesical approach (184 patients, 65.7%). Medical therapy had failed in all
      patients. Perioperative and outcome data were recorded and compared. RESULTS:
      There was no significant difference in patient age, prostate size, uroflow rate,
      mean International Prostate Symptom Score, operative blood loss, or total time of
      continuous bladder irrigation between the two groups. Mean operative time was
      significantly longer in the laparoscopy group, 95.1 +/- 32.9 minutes, v the open
      group at 54.7 +/- 19.7 minutes (P < 0.0001). Total catheter time was
      significantly shorter in the laparoscopy group (5.2 +/- 2.6 v 6.4 +/- 2.9 days; P
      < 0.001) as was length of hospital stay (6.3 +/- 1.9 v 7.7 +/- 2.4 days; P <
      0.0001). The most common complication between the two groups was hemorrhage,
      occurring in 27 (28.1%) patients in the laparoscopy group and 54 patients (29.3%)
      in the open group. Of the 19 urinary tract infections observed between the two
      groups, 18 occurred in the open group as well as all 9 cases of urinary sepsis.
      CONCLUSIONS: LSP offers advantages over OSP in terms of shorter catheter time,
      shorter hospital length of stay, and fewer urinary tract infections.

PMID- 19119804
TI  - Alkoxy chain effect on the viscosity of a quaternary ammonium ionic liquid:
      molecular dynamics simulations.
AB  - The viscosity of ionic liquids based on quaternary ammonium cations is reduced
      when one of the alkyl chains is replaced by an alkoxy chain ( Zhou et al. Chem.
      Eur. J. 2005 , 11 , 752. ). A microscopic picture of the role played by the ether
      function in decreasing the viscosity of quaternary ammonium ionic liquids is
      provided here by molecular dynamics (MD) simulations. A model for the ionic
      liquid N-ethyl-N,N-dimethyl-N-(2-methoxyethyl)ammonium
      bis(trifluoromethanesulfonyl)imide, MOENM(2)E TFSI, is compared to the
      tetraalkylammonium counterpart. The alkoxy derivative has lower viscosity, higher
      ionic diffusion coefficients, and higher conductivity than the tetraalkyl system
      at the same density and temperature. A clear signature of the ether function on
      the liquid structure is observed in cation-cation correlations, but not in anion
      anion or anion-cation correlations. In both the alkyl and the alkoxy ionic
      liquids, there is aggregation of long chains of neighboring cations within
      micelle-like structures. The MD simulations indicate that the less effective
      assembly between the more flexible alkoxy chains, in comparison to alkyl chains,
      is the structural reason for higher ionic mobility in MOENM(2)E TFSI.

PMID- 19119805
TI  - What affects the results of a laparoscopic adrenalectomy for pheochromocytoma?
      Evaluation with respect to intraoperative blood pressure and state of tumor.
AB  - PURPOSE: To investigate the factors that affect the operative data and to
      evaluate the validity of a laparoscopic adrenalectomy (LA) for pheochromocytoma.
      PATIENTS AND METHODS: Between July 1993 and January 2008, 172 LAs were performed
      in this department, and 34 of them were for pheochromocytoma. The characteristics
      and operative data of LAs for pheochromocytoma were examined with respect to the
      intraoperative systolic blood pressure (SBP) and the side of tumor. RESULTS: The
      intraoperative SBP rose to 180 mm Hg or more in 17 (50%) cases of LAs for
      pheochromocytomas. The analysis of SBP (<180 versus >180 mm Hg), however, showed
      that there were no differences in the operative data between the two groups. The
      tumor size was significantly associated with operative time (P < 0.05) or the
      blood loss (P < 0.05) in an LA for pheochromocytoma. The blood loss in LAs for
      right adrenal tumors was greater (150 versus 79 mL) than for left tumors (P <
      0.01). In particular, some procedures for right large tumors had considerable
      blood loss and long procedural time. In a comparison of the operative data
      between pheochromocytoma and other adrenal tumors, the tumor was larger (4.3
      versus 2.5 cm) and the blood loss was greater (100 versus 30 mL) than for other
      adrenal tumors. CONCLUSIONS: The operative data showed no correlation with the
      intraoperative high SBP, but they were associated with the tumor state. Although
      the procedure seems to be influenced by the size and state of tumor, LA is not
      contraindicated for pheochromocytoma, and it can therefore be performed safely.

PMID- 19119806
TI  - Theoretical investigation of N-nitrosodimethylamine formation from dimethylamine
      nitrosation catalyzed by carbonyl compounds.
AB  - The carbonyl-compound-catalyzed nitrosation of amines to form carcinogenic
      nitrosamines under nonacidic condition is different from the classic nitrosation
      via acidification of nitrite anion. The mechanistic pathways of N
      nitrosodimethylamine (NDMA) formation by the reactions of dimethylamine (DMA)
      with the nitrite anion catalyzed by carbonyl compounds have been investigated
      using the DFT/B3LYP method at the 6-311+G(d,p) level. The computational results
      show that the energy barriers of the nucleophilic addition reaction, which were
      calculated as 27-40 kcal/mol, increase significantly with methylation but vary
      slightly with chloromethylation on the carbonyl group. Comparison of energy
      barriers of this nucleophilic addition reaction and the electrophilic
      substitution reaction indicates that the former is the rate-determining step,
      from which the order of the catalytic activity is obtained as formaldehyde >
      chloral > acetaldehyde > acetone. Furthermore, analysis of electronic and steric
      effects on catalytic activity reveals that electron-withdrawing substituents
      decrease the energy barrier but electron-donating substituents and steric
      hindrance will block this catalytic reaction. Based on this discovery, fluoral is
      proposed as a good catalyst for the nitrosation of DMA by nitrite anion, which
      has a calculated energy barrier of about 26 kcal/mol. The results obtained in
      this work will help elucidate the mechanisms of formation of nitrosamines.

PMID- 19119807
TI  - Laparoscopic radical nephrectomy for patients with pathologic T3b renal-cell
      carcinoma: the Johns Hopkins experience.
AB  - BACKGROUND AND PURPOSE: Surgical therapy for renal-cell carcinoma (RCC) with
      vascular involvement has traditionally been performed via an open approach. As
      laparoscopic techniques have improved, more surgeons are attempting laparoscopic
      nephrectomy for higher stage RCC. The goal of our study was to evaluate the
      safety and short-tem oncologic efficacy of laparoscopic radical nephrectomy in
      patients with renal vein involvement. PATIENTS AND METHODS: We reviewed the
      clinical and pathologic data for 37 patients who underwent a pure laparoscopic
      radical nephrectomy for RCC with renal vein thrombus from 2005 to 2008 by
      dedicated laparoscopic surgeons. Perioperative and oncologic outcomes were
      assessed. Median age of our study population was 65 years, and mean follow-up was
      14 months. RESULTS: Median pathologic tumor size was 7.5 cm. One (2.7%) patient
      needed conversion to an open procedure. Median estimated blood loss (EBL) was 200
      mL (interquartile range [IQR]) 100-850), and median length of stay (LOS) was 3
      days (range 3-5 d). The overall perioperative complication rate was 14%, and
      there were no perioperative mortalities. Of the 32 patients without metastatic
      disease at the time of surgery, 29 (91%) are alive without evidence of disease.
      CONCLUSION: Laparoscopic radical nephrectomy in the setting of renal vein
      thrombus is a complex surgical procedure that necessitates significant
      laparoscopic skills. Our data demonstrate that laparoscopic radical nephrectomy
      is safe and effective in patients with RCC who have renal vein involvement,
      albeit with short-term oncologic follow-up. Long-term follow-up in larger series
      of patients is necessary to further define the role of laparoscopic nephrectomy
      in this subset of patients.

PMID- 19119808
TI  - A technique to flush out renal stone fragments during percutaneous
      nephrolithotomy.
AB  - There are a number of graspers and baskets to snare and remove stones during
      percutaneous nephrolithotomy (PCNL). These instrumental techniques can, however,
      cause inadvertent trauma to the renal mucosa and can be time consuming.
      Increasingly, these graspers and baskets are disposable, which also has financial
      implications. We use a simple technique to flush out fragments from the kidney
      during PCNL. Once fragments have been identified as a size that can pass through
      the Amplatz sheath, a cut nasogastric tube is inserted through the sheath--if
      possible next to or behind the fragments. It is repeatedly moved forward and
      backward in a jerking motion while saline is instilled under some pressure to
      create some turbulence. This results in the mechanical flushing out of stone
      fragments. We have found this to be a safe, effective, and reliable technique of
      stone extraction during PCNL.

PMID- 19119809
TI  - Radiative recombination of spatially extended excitons in (ZnSe/CdS)/CdS
      heterostructured nanorods.
AB  - We report on organometallic synthesis of luminescent (ZnSe/CdS)/CdS semiconductor
      heterostructured nanorods (hetero-NRs) that produce an efficient spatial
      separation of carriers along the main axis of the structure (type II carrier
      localization). Nanorods were fabricated using a seeded-type approach by
      nucleating the growth of 20-100 nm CdS extensions at [000 +/- 1] facets of
      wurtzite ZnSe/CdS core/shell nanocrystals. The difference in growth rates of CdS
      in each of the two directions ensures that the position of ZnSe/CdS seeds in the
      final structure is offset from the center of hetero-NRs, resulting in a spatially
      asymmetric distribution of carrier wave functions along the heterostructure.
      Present work demonstrates a number of unique properties of (ZnSe/CdS)/CdS hetero
      NRs, including enhanced magnitude of quantum confined Stark effect and
      subnanosecond switching of absorption energies that can find practical
      applications in electroabsorption switches and ultrasensitive charge detectors.

PMID- 19119810
TI  - C=C bond cleavage on neutral VO3(V2O5)n clusters.
AB  - The reactions of neutral vanadium oxide clusters with alkenes (ethylene,
      propylene, 1-butene, and 1,3-butadiene) are investigated by experiments and
      density function theory (DFT) calculations. Single photon ionization through
      extreme ultraviolet radiation (EUV, 46.9 nm, 26.5 eV) is used to detect neutral
      cluster distributions and reaction products. In the experiments, we observe
      products (V(2)O(5))(n)VO(2)CH(2), (V(2)O(5))(n)VO(2)C(2)H(4),
      (V(2)O(5))(n)VO(2)C(3)H(4), and (V(2)O(5))(n)VO(2)C(3)H(6), for neural V(m)O(n)
      clusters in reactions with C(2)H(4), C(3)H(6), C(4)H(6), and C(4)H(8),
      respectively. The observation of these products indicates that the C=C bonds of
      alkenes can be broken on neutral oxygen rich vanadium oxide clusters with the
      general structure VO(3)(V(2)O(5))(n=0,1,2...). DFT calculations demonstrate that
      the reaction VO(3) + C(3)H(6) --> VO(2)C(2)H(4) + H(2)CO is thermodynamically
      favorable and overall barrierless at room temperature. They also provide a
      mechanistic explanation for the general reaction in which the C=C double bond of
      alkenes is broken on VO(3)(V(2)O(5))(n=0,1,2...) clusters. A catalytic cycle for
      alkene oxidation on vanadium oxide is suggested based on our experimental and
      theoretical investigations. The reactions of V(m)O(n) with C(6)H(6) and C(2)F(4)
      are also investigated by experiments. The products VO(2)(V(2)O(5))(n)C(6)H(4) are
      observed for dehydration reactions between V(m)O(n) clusters and C(6)H(6). No
      product is detected for V(m)O(n) clusters reacting with C(2)F(4). The mechanisms
      of the reactions between VO(3) and C(2)F(4)/C(6)H(6) are also investigated by
      calculations at the B3LYP/TZVP level.

PMID- 19119811
TI  - Pleomorphic copper coordination by Alzheimer's disease amyloid-beta peptide.
AB  - Numerous conflicting models have been proposed regarding the nature of the Cu(2+)
      coordination environment of the amyloid beta (Abeta) peptide, the causative agent
      of Alzheimer's disease. This study used multifrequency CW-EPR spectroscopy to
      directly resolve the superhyperfine interactions between Cu(2+) and the ligand
      nuclei of Abeta, thereby avoiding ambiguities associated with introducing point
      mutations. Using a library of Abeta16 analogues with site-specific (15)N-labeling
      at Asp1, His6, His13, and His14, numerical simulations of the superhyperfine
      resonances delineated two independent 3N1O Cu(2+) coordination modes, {N(a)(D1),
      O, N(epsilon)(H6), N(epsilon)(H13)} (component Ia) and {N(a)(D1), O,
      N(epsilon)(H6), N(epsilon)(H14)} (component Ib), between pH 6-7. A third
      coordination mode (component II) was identified at pH 8.0, and simulation of the
      superhyperfine resonances indicated a 3N1O coordination sphere involving nitrogen
      ligation by His6, His13, and His14. No differences were observed upon (17)O
      labeling of the phenolic oxygen of Tyr10, confirming it is not a key oxygen
      ligand in the physiological pH range. Hyperfine sublevel correlation (HYSCORE)
      spectroscopy, in conjunction with site-specific (15)N-labeling, provided
      additional support for the common role of His6 in components Ia and Ib, and for
      the assignment of a {O, N(epsilon)(H6), N(epsilon)(H13), N(epsilon)(H14)}
      coordination sphere to component II. HYSCORE studies of a peptide analogue with
      selective (13)C-labeling of Asp1 revealed (13)C cross-peaks characteristic of
      equatorial coordination by the carboxylate oxygen of Asp1 in component Ia/b
      coordination. The direct resolution of Cu(2+) ligand interactions, together with
      the key finding that component I is composed of two distinct coordination modes,
      provides valuable insight into a range of conflicting ligand assignments and
      highlights the complexity of Cu(2+)/Abeta interactions.

PMID- 19119813
TI  - Halide-stabilized LiBH4, a room-temperature lithium fast-ion conductor.
AB  - Solid state lithium conductors are attracting much attention for their potential
      applications to solid-state batteries and supercapacitors of high energy density
      to overcome safety issues and irreversible capacity loss of the currently
      commercialized ones. Recently, we discovered a new class of lithium super ionic
      conductors based on lithium borohydride (LiBH(4)). LiBH(4) was found to have
      conductivity as high as 10(-2) Scm(-1) accompanied by orthorhombic to hexagonal
      phase transition above 115 degrees C. Polarization to the lithium metal electrode
      was shown to be extremely low, providing a versatile anode interface for the
      battery application. However, the high transition temperature of the superionic
      phase has limited its applications. Here we show that a chemical modification of
      LiBH(4) can stabilize the superionic phase even below room temperature. By doping
      of lithium halides, high conductivity can be obtained at room temperature. Both
      XRD and NMR confirmed room-temperature stabilization of superionic phase for LiI
      doped LiBH(4). The electrochemical measurements showed a great advantage of this
      material as an extremely lightweight lithium electrolyte for batteries of high
      energy density. This material will open alternative opportunities for the
      development of solid ionic conductors other than previously known lithium
      conductors.

PMID- 19119812
TI  - New macrocyclic terbium(III) complex for use in RNA footprinting experiments.
AB  - Reaction of terbium triflate with a heptadentate ligand derivative of cyclen, L1
      = 2-[7-ethyl-4,10-bis(isopropylcarbamoylmethyl)-1,4,7,10-tetraazacyclododec-1-yl]
      N-isopropyl-acetamide, produced a new synthetic ribonuclease,
      [Tb(L1)(OTf)(OH(2))](OTf)(2).MeCN (C1). X-ray crystal structure analysis
      indicates that the terbium(III) center in C1 is 9-coordinate, with a capped
      square-antiprism geometry. While the terbium(III) center is tightly bound by the
      L1 ligand, two of the coordination sites are occupied by labile water and
      triflate ligands. In water, the triflate ligand is likely to be displaced,
      forming [Tb(L1)(OH(2))(2)](3+), which is able to effectively promote RNA
      cleavage. This complex greatly accelerates the rate of intramolecular
      transesterification of an activated model RNA phosphodiester, uridine-3'-p
      nitrophenylphosphate (UpNP), with k(obs) = 5.5(1) x 10(-2) s(-1) at 21 degrees C
      and pH 7.5, corresponding to an apparent second-order rate constant of 277(5) M(
      1) s(-1). By contrast, the analogous complex of an octadentate derivative of
      cyclen featuring only a single labile coordination site, [Tb(L2)(OH(2))](OTf)(3)
      (C2), where L2 = 2-[4,7,10-tris(isopropylcarbamoylmethyl)-1,4,7,10
      tetraazacyclododec-1-yl]-N-isopropyl-acetamide, is inactive.
      [Tb(L1)(OH(2))(2)](3+) is also capable of hydrolyzing short transcripts of the
      HIV-1 transactivation response (TAR) element, HIV-1 dimerization initiation site
      (DIS) and ribosomal A-site, as well as formyl methionine tRNA (tRNA(fMet)),
      albeit at a considerably slower rate than UpNP transesterification (k(obs) =
      2.78(8) x 10(-5) s(-1) for TAR cleavage at 37 degrees C, pH 6.5, corresponding to
      an apparent second-order rate constant of 0.56(2) M(-1)s(-1)). Cleavage is
      concentrated at the single-stranded "bulge" regions of these RNA motifs.
      Exploiting this selectivity, [Tb(L1)(OH(2))(2)](3+) was successfully employed in
      footprinting experiments, in which binding of the Tat peptide and neomycin B to
      the bulge region of the TAR stem-loop was confirmed.

PMID- 19119814
TI  - Hydrophilicity-controlled carbon aerogels with high mesoporosity.
AB  - Highly mesoporous carbon aerogels with hydrophilicity-controlled pore walls were
      synthesized using a unique approach that combines CO(2) supercritical drying and
      colloidal silica nanocasting. The samples were characterized using nitrogen
      adsorption at 77 K, water adsorption at 303 K, field-emission scanning electron
      microscopy (FE-SEM), thermogravimetric analysis, X-ray photoelectron
      spectroscopy, and Raman spectroscopy. The nitrogen adsorption revealed the
      presence of micropores and mesopores with narrow pore size distributions. The
      water adsorption suggested that the hydrophilicity of carbon aerogels can be
      controlled by the residual silica in their pore walls. The FE-SEM observation
      confirmed the presence of hierarchical mesostructures and the high mesoporosity.
      The high surface area, large nanopore volume, and hydrophilicity-controlled pore
      walls make these aerogels well-suited for many applications.

PMID- 19119815
TI  - Photoassisted overall water splitting in a visible light-absorbing dye-sensitized
      photoelectrochemical cell.
AB  - Iridium oxide nanoparticles stabilized by a heteroleptic ruthenium
      tris(bipyridyl) dye were used as sensitizers in photoelectrochemical cells
      consisting of a nanocrystalline anatase anode and a Pt cathode. The dye
      coordinated the IrO(2) x nH(2)O nanoparticles through a malonate group and the
      porous TiO(2) electrode through phosphonate groups. Under visible illumination
      (lambda > 410 nm) in pH 5.75 aqueous buffer, oxygen was generated at anode
      potentials positive of -325 mV vs Ag/AgCl and hydrogen was generated at the
      cathode. The internal quantum yield for photocurrent generation was ca. 0.9%.
      Steady-state luminescence and time-resolved flash photolysis/transient absorbance
      experiments were done to measure the rates of forward and back electron transfer.
      The low quantum yield for overall water splitting in this system can be
      attributed to slow electron transfer (approximately 2.2 ms) from IrO(2) x nH(2)O
      to the oxidized dye. Forward electron transfer does not compete effectively with
      the back electron transfer reaction from TiO(2) to the oxidized dye, which
      occurred on a time scale of 0.37 ms.

PMID- 19119816
TI  - The tandem Cope-type hydroamination/[2,3]-rearrangement sequence: a strategy to
      favor the formation of intermolecular hydroamination products and enable
      difficult cyclizations.
AB  - The tandem hydroamination/Meisenheimer rearrangement sequence was developed to
      address the issue of unfavorable reaction thermodynamics for intermolecular
      reactions of alkenes and to improve the scope of Cope-type hydroaminations. This
      tandem sequence allows intermolecular reactions of N-alkyl-N-methallylhydroxyl
      amines to be energetically more favorable: the N-oxide intermediate formed via
      Cope-type hydroamination, which can revert to the starting materials via a Cope
      elimination, can form a more stable neutral product via a [2,3]-Meisenheimer
      rearrangement. This tandem sequence also leads to increased efficiency in
      intramolecular systems as illustrated by syntheses of two alkaloids (coniine and
      norreticuline) featuring difficult hydroamination key steps.

PMID- 19119817
TI  - Chemically controlled amplified ratiometric fluorescence in surface-immobilized
      end-capped oligo(p-phenylene ethynylene)s.
AB  - Efficient photoexcitation energy transfer in extended pi-electron conjugated
      molecules is a key factor in applications of such systems as a gain media in
      signal-amplifying fluorescent chemodetectors. Here we report an unprecedented
      ratiometric fluorescence amplification phenomenon in the surface-immobilized
      monolayers of oligo(p-phenylene ethynylene)s end-capped with a lower energy gap
      receptor group. The process of covalent immobilization on the surface results in
      monolayer films with improved molecular organization, which display highly
      efficient excitation energy transfer to the lower energy receptor groups.
      Chemical transformation of a subtle fraction of the receptor groups on the
      surface leads to a very significant fluorescent ratiometric response. While
      fundamental understanding of this unusual "turn-on" amplification phenomenon
      requires further studies, it can be used to develop thin-film ratiometric
      fluorescent chemosensors with improved optical gain.

PMID- 19119818
TI  - Discrimination and identification of flavors with catalytic nanomaterial-based
      optical chemosensor array.
AB  - A cross-reactive chemiluminescence (CL) sensor array based on catalytic
      nanomaterials was constructed for the discrimination and identification of
      flavors in cigarettes. A total of 21 nanomaterials, including metal oxides, metal
      oxides deposited on carbon nanotubes (CNTs), gold nanoparticles deposited on
      metal oxides, and carbonate, have been carefully selected as sensing elements of
      the array. Each flavor gives its unique CL pattern from the array, which is able
      to be employed for the discrimination and identification of flavors. Hierarchical
      cluster analysis (HCA) and linear discriminant analysis (LDA) were used to
      analyze the patterns. The obtained CL patterns are temperature dependent, thus
      additional discrimination power could be provided by changing the working
      temperature of the array. Quantification of the flavors has been performed
      according to the emission intensity on the specific sensing element. The linear
      ranges of the sensor array for the flavors are in the range of 20-2000 ppmv with
      the limits of detection below 10 ppmv, which vary with the kinds of flavors. Six
      brands of cigarettes have been discriminated by their CL patterns obtained with
      the present sensor array. The robust and reversible response of this array,
      combined with its simple instrumentation, indicates the promise of this array for
      real world application.

PMID- 19119819
TI  - Photochromic diarylethene-containing ionic liquids and N-heterocyclic carbenes.
AB  - The design and synthesis of a series of photochromic diarylethene-containing
      Arduengo-type N-heterocyclic carbenes (NHCs) of gold(I), silver(I) and
      palladium(II) and their imidazolium salt precursors are reported. Reversible
      photochromic behavior was observed. The open form and the closed form also show
      different luminescence properties. The electronic and conformational/steric
      changes associated with the photocyclization and photocycloreversion reactions
      may open up new opportunities for the discovery of new classes of photochromic
      ligands and metal-containing materials and catalysts with photoswitchable
      functions and activities and regio-/enantioselectivities.

PMID- 19119820
TI  - Surfactant control of gas transport and reactions at the surface of sulfuric
      acid.
AB  - Aerosol particles in the atmosphere are tiny chemical reactors that catalyze
      numerous reactions, including the conversion of benign gases into ozone
      destroying ones. In the lower stratosphere, these particles are often supercooled
      mixtures of water and sulfuric acid. The different species present at the surface
      of these droplets (H(2)O, H(3)O(+), HSO(4)(-), H(2)SO(4), and SO(4)(2-)) stand at
      the "gas-liquid frontier"; as the first to be struck by impinging molecules,
      these species provide the initial environment for solvation and reaction.
      Furthermore, aerosol particles may contain a wide range of organic molecules,
      some of which migrate to the surface and coat the droplet. How do ambient gases
      dissolve in the droplet if it is coated with an organic layer? At one extreme,
      monolayer films of insoluble, long-chain alcohols can dramatically reduce gas
      transport, packing so tightly at the surface of water that they impede water
      evaporation by factors of 10,000 or more. Shorter chain surfactants are expected
      to pack less tightly, but we wondered whether these incomplete monolayers also
      block gas transport and whether this system could serve as a model for
      understanding the surfaces of atmospheric aerosol particles. To address these
      questions, our research focuses on small, soluble surfactants such as butanol and
      hexanol dissolved in supercooled sulfuric acid. These amphiphilic molecules
      spontaneously segregate to the surface and coat the acid but only to a degree.
      Gas-liquid scattering experiments reveal that these porous films behave in
      surprisingly diverse ways: they can impose a barrier (to N(2)O(5) hydrolysis), be
      "invisible" (to water evaporation), or even enhance gas uptake (of HCl). The
      transition from obstacle to catalyst can be traced to specific interactions
      between the surfactant and each gas. For example, the hydrolysis of N(2)O(5) may
      be impeded because of its large size and because alcohol molecules that straddle
      the interface limit contact between N(2)O(5) and its H(3)O(+) and H(2)O reaction
      partners. However, these same alcohol molecules assist HCl dissociation because
      the alcohol OH groups provide extra interfacial protonation sites. Interestingly,
      butanol does not impede water evaporation, in part because the butyl chains pack
      much more loosely than insoluble, long-chain surfactants. Through these
      investigations, we hope to gain insight into the mechanisms by which surfactants
      on sulfuric acid and other aqueous solutions affect transport and reactivity at
      the gas-liquid interface.

PMID- 19119821
TI  - Telemedicine and e-Health-a year-end summary for 2008.

PMID- 19119822
TI  - Telethinking with Jonathan Linkous interviewed by Charles R. Doarn.

PMID- 19119823
TI  - Human factors in telemedicine.

PMID- 19119824
TI  - Three modalities in cardiovascular telemedicine.

PMID- 19119825
TI  - Value versus user fees: perspectives of patients before and after using a web
      based portal for management of diabetes.
AB  - The objective of this work was to rate the potential or actual usefulness of 15
      features of a Web-based portal for diabetes management and assess whether
      patients would be willing to pay user fees for portal access. We used a
      combination of qualitative methods (focus group discussions) and quantitative
      methods (survey responses) to examine patients' perspectives. We enrolled 21
      patients before the diabetes-specific portal was released ("preportal" group) and
      18 patients after it was released ("portal-users" group). The two groups were
      similar except that 67% of preportal patients and 100% of portal users were
      Internet users. Overall, portal features that were rated most favorably were the
      online calculator to estimate blood glucose control (characterized as "very
      useful" by 74% of patients), appointment reminder systems (74%), e-mail access to
      health team (74%), personal tracking logs (69%), and online scheduling (69%).
      More patients from the preportal group than the portal-users group favored
      personal logs (86% versus 50%; p = 0.015) and opportunities to form interest
      groups (62% versus 28%; p = 0.034). Of the 30 patients who assigned a dollar
      amount for 1 month of portal access, 20 assigned zero dollars. Discussions about
      payment focused on equity and access. Because fees are expected to discourage
      portal usage, many patients believed that the potential benefits associated with
      self-management would not be realized. Others felt that the health system would
      benefit financially from a portal and should therefore absorb the costs. Even if
      portals are valued, patients may be resistant to paying for them. This opposition
      stems from concerns about fairness and from the recognition that health systems
      may experience cost savings if patients manage their diabetes successfully.

PMID- 19119826
TI  - Development of a portable device for telemonitoring of physical activities during
      sleep.
AB  - Low motor activity levels and prolonged episodes of uninterrupted immobility are
      characteristics of sleep. In clinical practice, the use of polysomnographic (PSG)
      recording is a standard procedure to assess sleep. However, PSG is not suitable
      for long-term monitoring in the home environment. This paper describes the
      development of a portable telemonitoring device that detects movements of a
      subject by conductive mats, and evaluates sleep stages via physical activity
      data. The device itself also serves as a Web server. Doctors and caregivers can
      access real-time and historical data via an IE browser or a remote application
      program for telemonitoring of physical activities and sleep/awake states during
      sleep, while the patients stay in their own homes. In our validation test with
      four normal subjects and four arousal subjects, this system showed a good
      performance in locating sleep epochs of a subject. The sensitivity of locating
      sleep epochs was 89.5% and the average positive prediction value was 94.8%, with
      a specificity of 84.3%. This device is not intended to be a diagnosis device,
      instead, it is to be used as a home telehealth tool for monitoring physical
      activity and sleep/awake states. This portable telemonitoring device provides a
      convenient approach to better understand and recognize a subject's sleep pattern
      through long-term sleep monitoring in the home environment.

PMID- 19119827
TI  - Implementation of telenursing within home healthcare.
AB  - The implementation of telenursing within home healthcare of leg wounds is an
      innovative development initiative that focuses on patients and to some extent
      next-of-kin in collaboration with nurses. Eleven patients and nine nurses
      participated in the study. The methods for data collection were surveys, field
      notes descriptions, and care charts, as well as digital photos of leg wounds and
      videotaped observations. The results show that the utility of virtual concept is
      that continual learning takes place for both patients and nurses. The patients
      felt positively about being able to via videophone see the staff caring for them,
      and seeing a face inspired a sense of security, which had a calming effect. The
      learning for nurses lay in the everyday work with leg wounds and their care as
      experiences were taken advantage of with the assistance of the interactive
      technique. The nurses felt that their time at work was better utilized and that
      the virtual communication between patients and nurses constituted a humane
      complement in home healthcare.

PMID- 19119828
TI  - Novel efficient and secure medical data transmission on WiMAX.
AB  - This paper discusses an improved technique for bandwidth-efficient and secure
      transmission of medical records over simulated orthogonal frequency division
      multiplexing (OFDM)-based Worldwide Interoperability for Microwave Access
      (WiMAX)/IEEE 802.16 physical layer. Medical data compaction along with security
      has been achieved by embedding electrocardiogram (ECG) data into Haar wavelet
      coefficients of an x-ray image that is transmitted over the channel. The
      compaction ratio and peak signal-to-noise ratio (PSNR) between the transmitted
      and received x-ray images for visual clinical performance have been evaluated. It
      is shown that 12.5% data compaction along with true reception of ECG signal can
      be achieved for channel signal-to-noise ratio (SNR) >or= 9.6 dB while the
      achieved PSNR was 55.97 dB. The PSNR value is well above the minimum acceptable
      35 dB level, making it potentially useful for secure and bandwidth-efficient
      transmission of clinical records.

PMID- 19119829
TI  - Videophone-delivered voice therapy: a comparative analysis of outcomes to
      traditional delivery for adults with Parkinson's disease.
AB  - Individuals with idiopathic Parkinson's disease (IPD) usually develop a speech
      disorder characterized by reduced loudness, hoarse and breathy voice, monotony of
      pitch, short rushes of speech, and imprecise consonants. The inability to
      effectively communicate impairs their ability to function in society and quality
      of life. A successful program developed to improve speech in these individuals is
      the Lee Silverman Voice Treatment (LSVT). A critical component of this treatment
      is intense daily therapy for 4 weeks, a regimen that is difficult for many
      elderly patients to complete. Treatment delivered through videophones placed in
      the homes of individuals with IPD offers an alternative and could improve
      accessibility of treatment if the results were the same. This study compared the
      outcomes of LSVT delivered via videophones to the outcomes of traditional
      treatment delivered face-to-face.

PMID- 19119830
TI  - Ten-year experience of a private nonprofit telepsychiatry service.
AB  - This paper reports the results of a satisfaction survey of telepsychiatry
      patients at a rural community mental health clinic that had been providing
      psychiatric services solely via telemedicine for 10 years. The survey examined
      the perceived telepsychiatric session quality over a relatively long period of
      time with patients who had been utilizing the services for a number of years or
      over multiple sessions. One-page optional anonymous surveys were distributed from
      December 1, 2006, through March 30, 2007, covering 230 telepsychiatry patients,
      approximately 90% of current telepsychiatry patients at the agency. Of these, 76
      patients responded, a 33.0% return rate. Among the respondents, satisfaction was
      generally very high, with telemedicine services provided over a period of up to
      10 years perceived to be of similar (no worse) quality than in-person services.
      Results were further analyzed by gender, age, and number of telemedicine sessions
      experienced. Female patients appeared more accepting of the quality of medical
      care via telemedicine than male patients. Patients aged 20-49 had much higher
      acceptance rates than patients younger than 20 or older than 49. The least
      positive responses toward telemedicine were from patients in their 50s. Patients
      who had experienced 5 to 10 telemedicine sessions were more likely than patients
      who had experienced fewer than 5 to report that their sessions now run more
      smoothly than their initial sessions. Patients in their 20s and 30s reported the
      least need to have a clinician in the room with them to make them feel
      comfortable during their telemedicine sessions. Eight percent of respondents
      reacted negatively to the presence of a clinician in the room with them during
      their telemedicine sessions.

PMID- 19119831
TI  - Generational differences in acceptance of technology.
AB  - The twofold purpose of this study was to first determine if telemedicine would
      offer a time efficient use of faculty mentoring of students performing
      traditional history and physical examinations on elders residing in an
      independent living facility (ILF). The second purpose was to determine if
      differences exist between the two groups' perceptions of technology: from
      telemedicine to cell phones. Two groups consisting of two generations
      participated in a telemedicine distance mentoring study. One group included 25
      elderly residing in an independent living facility (group 1). The second group
      was comprised of 25 physician assistant program (PA) students (group 2). Group 1
      recognized the convenience telemedicine offered for easier access to doctors.
      Group 2 recognized that telemedicine could potentially improve time efficiency of
      their practice. Both groups were generally unaware and uninformed about the
      technological devices commonly used by the opposite group. Group 1 used
      technological devices for improving basic sensory, balance, and gait disorders as
      well as contributing to a sense of safety and security, whereas group 2 mostly
      utilized telecommunications technology. Both groups acquired knowledge of
      technological innovations that have a direct effect on their lives and both
      groups shared the same perceptions of telemedicine's positive influence on
      improving access to healthcare services both for users as well as providers.

PMID- 19119832
TI  - Would people pay for text messaging health reminders?
AB  - The aim of this study is to determine the time and financial limitations that
      people would accept for using a telehealth service consisting of wireless text
      messaging reminders to improve adherence to a recommended healthy regimen. An
      empirical study based on a 1-month trial of a prototype system that studied
      adherence to a specified healthy behaviour was conducted. Fifty-one participants
      received daily cell phone text messaging reminders on taking one vitamin C pill
      daily for preventive reasons. At the end of the trial they answered a survey
      regarding their willingness to pay for and to stay with such a service, if
      offered. If usage were free, only 45% of the participants would continue to use
      it for a long indefinite period of time. If the usage were for a fee, 29% of the
      participants would use the service just a few weeks; 28% would use it an
      indefinite period of time if they could see its usefulness and if the cost were
      reasonable. The median amount indicated by the participants as a reasonable
      monthly fee for such a service was $5. Although the study did not evaluate
      perceived usefulness to use the telehealth service explicitly, a benefit
      perception proved to condition participant willingness to use the service and to
      pay for it, if necessary. If people perceive usefulness, they want to use the
      service, even for a fee. A free service would not be used if it is not perceived
      as beneficial.

PMID- 19119833
TI  - New wearable system for step-counting telemonitoring and telerehabilitation based
      on the Codivilla spring.
AB  - During stroke rehabilitation at home, the most used equipment is the Codivilla
      spring for both bilateral and one-side stroke damage. A novel Codivilla spring
      prosthesis has been electronically sensorized in order to allow new
      functionalities pertinent to telerehabilitation, such as the step counting and
      biofeedback mapping of gait-phases. The principal elements of the electronics are
      a couple of force-sensing resistors affixed in the plantar area of the
      prosthesis, and a wearable unit with a microprocessor-based on Microchip
      technology (Microchip Technology, Inc., Chandler, AZ) for data processing and a
      telemetric system based on Aurel technology (Aurel, Modigliana, Italy) for data
      tansfer. While ambulating, the foot-sensing resistors detect the pressure of the
      foot-tip and heel. The microprocessor provides step-counting on the basis of an
      algorithm. The microprocessor also drives two vibrotactile actuators (one at the
      foot-tip and the other at the heel). These actuators are fixed at the level of
      the belt directly in contact with the skin and give biofeedback mapping of the
      gait-phases to the patient wearing the prosthesis, who can then walk without
      looking at his or her feet. The sensorized prosthesis was tested on six subjects
      undergoing stroke rehabilitation at level 2 of the Tinetti test. These subjects
      performed five repetitions of 100 steps with three different instructions (fast,
      slow, and normal). The mean error was lower than 0.6%. A test conducted by means
      of Cosmed devices (Cosmed USA, Chicago, IL) also showed that the biofeedback
      function provided by means of the actuators diminished the energy expenditure by
      0.7% in mean value. The next phase will be the optimization of the equipment for
      long-term medical application in a patient's home.

PMID- 19119834
TI  - Overview of telehealth activities in speech-language pathology.
AB  - It is estimated that 10% of the world's population, approximately 650 million
      people, have some form of disability. Population growth, aging, and medical
      advances that preserve and prolong life have increased demands for health and
      rehabilitation services. Recent predictions indicate a shortage of speech
      language pathologists and other rehabilitation specialists to provide care for
      individuals with disabilities. The application of telemedicine and telehealth
      technologies offers effective solutions to this challenge. An extensive
      literature review was conducted that included technical reports, websites,
      publications from the American Speech-Language-Hearing Association, and peer
      reviewed journal articles of telehealth applications in speech-language
      pathology. Various applications of telehealth in speech-language pathology are
      described including types of technology, patient and clinician satisfaction,
      advantages of using telehealth, challenges and barriers to application, and
      future directions. This review provides a strong foundation for broader
      applications of telehealth technologies in this area of healthcare.

PMID- 19119835
TI  - Care Coordination/Home Telehealth: the systematic implementation of health
      informatics, home telehealth, and disease management to support the care of
      veteran patients with chronic conditions.
AB  - Between July 2003 and December 2007, the Veterans Health Administration (VHA)
      introduced a national home telehealth program, Care Coordination/Home Telehealth
      (CCHT). Its purpose was to coordinate the care of veteran patients with chronic
      conditions and avoid their unnecessary admission to long-term institutional care.
      Demographic changes in the veteran population necessitate VHA increase its
      noninstitutional care (NIC) services 100% above its 2007 level to provide care
      for 110,000 NIC patients by 2011. By 2011, CCHT will meet 50% of VHA's
      anticipated NIC provision. CCHT involves the systematic implementation of health
      informatics, home telehealth, and disease management technologies. It helps
      patients live independently at home. Between 2003 and 2007, the census figure
      (point prevalence) for VHA CCHT patients increased from 2,000 to 31,570 (1,500%
      growth). CCHT is now a routine NIC service provided by VHA to support veteran
      patients with chronic conditions as they age. CCHT patients are predominantly
      male (95%) and aged 65 years or older. Strict criteria determine patient
      eligibility for enrollment into the program and VHA internally assesses how well
      its CCHT programs meet standardized clinical, technology, and managerial
      requirements. VHA has trained 5,000 staff to provide CCHT. Routine analysis of
      data obtained for quality and performance purposes from a cohort of 17,025 CCHT
      patients shows the benefits of a 25% reduction in numbers of bed days of care,
      19% reduction in numbers of hospital admissions, and mean satisfaction score
      rating of 86% after enrolment into the program. The cost of CCHT is $1,600 per
      patient per annum, substantially less than other NIC programs and nursing home
      care. VHA's experience is that an enterprise-wide home telehealth implementation
      is an appropriate and cost-effective way of managing chronic care patients in
      both urban and rural settings.

PMID- 19119837
TI  - Toward the design of a wearable system for the remote monitoring of epileptic
      crisis.
AB  - A primary or secondary compulsive epileptic crisis (EC) causes a sudden loss of
      consciousness. During the acute phase, the subject is completely unable to
      interact with the environment. Electroencepholographic (EEG) signals show a
      significant frequency spectrum centered at 6.5 Hz during an EC. Telemonitoring of
      EEG signals could be useful to remotely communicate the occurrence of an EC. The
      purpose of this work was to design and construct a system based on a frequency
      algorithm to detect an EC. In addition, the system must remotely communicate the
      occurrence of the EC and its geographical coordinates through the national global
      system for mobile communications (GSM) network. A wearable system for the
      detection of the EC and the communication has been proposed. The EEG signals are
      multiplexed, amplified, and low pass filtered at 20 Hz by means of the
      conditioning unit. As soon as an EC event is detected by a signal-processing unit
      based on the microP DSPic33fj12gp (Microchip Technolgoy, Inc., Chadler, AZ), a
      trigger is sent to a communication unit based on two separate GPS/GSM FT596K9
      (Siemens, Berlin, Germany) units. The communication unit then sends an SMS
      message with an alarm and the coordinates of the subject. The final weight of the
      complete system developed using surface-montage-technology was equal to 3,760 mN,
      with a volume equal to 282 cm(3). Each component of the wearable system was
      designed separately and integrated. The system was tested in each component part
      and simulated in a closed loop. In particular, the system as a whole was
      simulated using 20 EEG rough traces (10 positive and 10 negative) in describing
      an EC. In both cases, the system did not show failures.

PMID- 19119836
TI  - The evaluation of patients with hepatitis C living in rural California via
      telemedicine.
AB  - Patients with hepatitis C who live in rural and low socioeconomic communities
      often lack access to specialty care. Over the past 7 years, we have provided
      telemedicine consultations at the Peach Tree Clinic, located in rural northern
      California. We performed a retrospective analysis of our experience. During this
      time period we provided consultations for 103 patients with hepatitis C; 37% had
      cirrhosis, and 64% had never undergone therapy with interferon and ribavirin.
      Twenty-three percent of the patients were candidates for therapy. The most common
      contraindication to therapy was the severity of their disease and the risk of
      decompensation. Fifteen patients were evaluated for liver transplant; 2 were
      listed but none survived long enough to receive a liver transplant. Our data
      suggest that there is a large number of patients with hepatitis C and advanced
      liver disease living in rural communities, some of whom may need treatment or
      liver transplant. Telemedicine is an effective tool for identifying and treating
      patients with hepatitis C who live in rural communities.

PMID- 19119838
TI  - American Telemedicine Association special interest groups: an update on goals and
      activities.

PMID- 19119839
TI  - Physicochemical and hypocholesterolemic characterization of oxidized oat beta
      glucan.
AB  - 2,2,6,6-Tetramethyl-1-piperidine oxoammonium ion (TEMPO)-mediated oxidation was
      applied to oat beta-glucans, and the physicochemical and hypocholesterolemic
      properties of the resulting derivatives were investigated. The (13)C NMR spectra
      revealed that C6 primary alcohol groups were selectively oxidized into carboxyl
      groups. The oxidized derivatives exhibited enhanced water solubility and improved
      in vitro bile acid binding capacity. When hypercholesterolemic rats were fed
      diets containing the oxidized beta-glucan, the levels of triglyceride, total
      cholesterol, LDL-C, and VLDL-C in the rats significantly decreased (p < 0.05),
      consequently improving the serum lipid profiles. Dietary supplementation with
      beta-glucans reduced also the total cholesterol level in liver. Furthermore, more
      fecal eliminations of total cholesterol and triglyceride were observed, which
      were favorably correlated to their reduced levels in the serum and liver. As a
      result, oxidized oat beta-glucan exhibits potential use as an active cholesterol
      lowering ingredient.

PMID- 19119841
TI  - Base-free molybdenum and tungsten bicyclic silylene complexes stabilized by a
      homoaromatic contribution.
AB  - Unprecedented base-free bicyclic silylene complexes of molybdenum and tungsten
      3a,b (a, M = Mo; b, M = W) were prepared by the reaction of the calcium salt of
      1,2,3,4-tetrakis(di-tert-butylmethylsilyl)tetrasilabicyclo[1.1.0]butane-2,4-diide
      2(2-) x Ca(2+) with Cp(2)MCl(2) (M = Mo, W). The unusual structural features of
      3b (long SiW double bond, short skeletal (sp(2)-Si)-(sp(3)-Si) bonds and
      extremely long Si-Si bridge) are indicative of a contribution from the
      zwitterionic resonance form W(delta-)-Si(delta+), in which the electrophilic
      silicon center is stabilized by the Si(3)-homoaromatic conjugation. This was
      supported by the theoretical calculations (NBO, NPA) revealing the presence of
      pi(WSi) and sigma(Si-Si bridge) interactions.

PMID- 19119842
TI  - Developing and optimizing an immunoaffinity cleanup technique for determination
      of quinolones from chicken muscle.
AB  - An immunoaffinity chromatographic method was developed using an antibody mediated
      immunosorbent to selectively extract and purify 10 quinolones (marbofloxacin,
      norfloxacin, ciprofloxacin, lomefloxacin, danofloxacin, enrofloxacin, difloxacin,
      sarafloxacin, oxolinic acid, and flumequine) in chicken muscle followed by HPLC.
      The operating conditions of the immunoaffinity chromatography (IAC) column were
      optimized, and the IAC has been successfully used for the isolation and
      purification of 10 quinolones from chicken muscle tissue. The optimized
      immunoaffinity column sample cleanup procedure combined with HPLC coupling to
      fluorescence detection afforded low limits of detection (0.1 ng g(-1) for
      danfloxacin and 0.15 ng g(-1) for all other quinolones tested). The method was
      also applied to determine quinolone residues in commercial muscle samples.

PMID- 19119843
TI  - Synthesis of fluorescent carbohydrate-protected Au nanodots for detection of
      Concanavalin A and Escherichia coli.
AB  - This study describes a novel, simple, and convenient method for the preparation
      of water-soluble biofunctional Au nanodots (Au NDs) for the detection of
      Concanavalin A (Con A) and Escherichia coli (E. coli). First, 2.9 nm Au
      nanoparticles (Au NPs) were prepared through reduction of HAuCl(4).3H(2)O with
      tetrakis(hydroxymethyl)phosphonium chloride (THPC), which acts as both a reducing
      and capping agent. Addition of 11-mercapto-3,6,9-trioxaundecyl-alpha-D
      mannopyranoside (Man-SH) onto the surfaces of the as-prepared Au NPs yielded the
      fluorescent mannose-protected Au nanodots (Man-Au NDs) with the size and quantum
      yield (QY) of 1.8 (+/-0.3) nm and 8.6%, respectively. This QY is higher than
      those of the best currently available water-soluble, alkanethiol-protected Au
      nanoclusters. Our fluorescent Man-Au NDs are easily purified and by multivalent
      interactions are capable of sensing, under optimal conditions, Con A with high
      sensitivity (LOD = 75 pM) and remarkable selectivity over other proteins and
      lectins. To the best of our knowledge, this approach provided the lowest LOD
      value for Con A when compared to the other nanomaterials-based detecting method.
      Furthermore, we have also developed a new method for fluorescence detection of E.
      coli using these water-soluble Man-Au NDs. Incubation with E. coli revealed that
      the Man-Au NDs bind to the bacteria, yielding brightly fluorescent cell clusters.
      The relationship between the fluorescence signal and the E. coli concentration
      was linear from 1.00 x 10(6) to 5.00 x 10(7) cells/mL (R(2) = 0.96), with the LOD
      of E. coli being 7.20 x 10(5) cells/mL.

PMID- 19119844
TI  - Boron nitride nanotubes are noncytotoxic and can be functionalized for
      interaction with proteins and cells.
AB  - We report the discovery that boron nitride nanotubes (BNNTs), isosteres of CNTs
      with unique physical properties, are inherently noncytotoxic. Furthermore, we
      developed a biomemetic coating strategy to interface BNNTs with proteins and
      cells. Finally, we showed that BNNTs can deliver DNA oligomers to the interior of
      cells with no apparent toxicity. This work suggests that BNNTs may be superior to
      CNTs for use as biological probes and in biomaterials.

PMID- 19119845
TI  - Standardized ileal digestibility of reactive lysine in distillers dried grains
      with solubles fed to growing pigs.
AB  - The Maillard reaction can occur during the production of distillers dried grains
      with solubles (DDGS) as a result of the addition of condensed solubles to the wet
      distillers cake during drying. The Maillard reaction can lead to the formation of
      unavailable or unreactive lysine as a result of binding of reducing sugars to the
      epsilon-NH(2) group of Lys. The Lys that remains unbound is called reactive Lys.
      The conventional procedure to measure the apparent ileal digestibility (AID) and
      standardized ileal digestibility (SID) of total Lys in DDGS may overestimate the
      amount of digestible Lys in DDGS because this procedure does not discount the
      unreactive Lys in DDGS, although only the reactive Lys is available for use by
      animals. By measuring the ileal digestibility of only the reactive Lys, it is
      expected that estimation of the amount of bioavailable Lys in DDGS will be more
      accurate. The objective of this experiment, therefore, was to test the hypothesis
      that the concentrations of AID and SID of reactive Lys are lower than the
      concentrations of AID and SID of total Lys in DDGS. Twelve DDGS sources, diets
      containing each of these 12 DDGS sources, and ileal digesta from pigs fed these
      diets were obtained from two previous experiments. Samples were guanidinated with
      O-methylisourea and analyzed for the concentration of homoarginine. It was
      assumed that only the reactive Lys, but not the unreactive Lys, would be
      transformed to homoarginine. This procedure, therefore, allows the separate
      measurement of reactive and unreactive Lys in DDGS-containing diets and ileal
      digesta. Subsequently, the ileal digestibility of reactive Lys can be calculated.
      The AID and SID of reactive Lys (percent) and the concentration of apparent ileal
      and standardized ileal digestible reactive Lys (g/kg) were then calculated and
      compared with the previously calculated values for total Lys. Results showed that
      only 76% of the total Lys in DDGS is reactive. The AID and SID of reactive Lys in
      DDGS (average = 60.1 and 66.9%, respectively) were similar to the AID and SID of
      total Lys (60.9 and 66.5%, respectively). When calculated as grams per kilogram,
      the concentration of standardized ileal digestible reactive Lys (3.9 g/kg) was
      lower (P < 0.05) than the concentration of standardized ileal digestible total
      Lys (5.1 g/kg). Thus, 24% of the concentration of standardized ileal digestible
      total Lys that was calculated using the conventional ileal AA digestibility
      procedure was unreactive Lys. The implication of these results is that the
      conventional AA digestibility procedure overestimates the concentration of
      digestible Lys in DDGS, and measurement of the concentration of digestible
      reactive Lys may more accurately estimate the amount of Lys in DDGS that is
      bioavailable to the pig.

PMID- 19119846
TI  - Phenolate hydroxylation in a bis(mu-oxo)dicopper(III) complex: lessons from the
      guanidine/amine series.
AB  - A new hybrid permethylated-amine-guanidine ligand based on a 1,3-propanediamine
      backbone (2L) and its Cu-O2 chemistry is reported. [(2L)CuI(MeCN)]1+ complex
      readily oxygenates at low temperatures in polar aprotic solvents to form a bis(mu
      oxo)dicopper(III) (O) species (2b), similar to the parent bis-guanidine ligand
      complex (1b) and permethylated-diamine ligand complex (3b). UV-vis and X-ray
      absorption spectroscopy experiments confirm this assignment of 2b as an O
      species, and full formation of the 2:1 Cu-O2 complex is demonstrated by an
      optical titration with ferrocene-monocarboxylic acid (FcCOOH). The UV-vis spectra
      of 1b and 2b with guanidine ligation show low-intensity visible features assigned
      as guanidine pi --> Cu2O2 core transitions by time-dependent density functional
      theory (TD-DFT) calculations. Comparison of the reactivity among the three
      related complexes (1b-3b) with phenolate at 195 K is particularly insightful as
      only 2b hydroxylates 2,4-di-tert-butylphenolate to yield 3,5-di-tert
      butylcatecholate (>95% yield) with the oxygen atom derived from O2, reminiscent
      of tyrosinase reactivity. 1b is unreactive, while 3b yields the C-C radical
      coupled bis-phenol product. Attenuated outer-sphere oxidative strength of the O
      complexes and increased phenolate accessibility to the Cu2O2 core are attributes
      that correlate with phenolate hydroxylation reactivity observed in 2b. The
      comparative low-temperature reactivity of 1b-3b with FcCOOH (O-H BDE 71 kcal mol(
      1)) to form the two-electron, two-proton reduced bis(mu-hydroxo)dicopper(II,II)
      complex is quantitative and presumably precedes through two sequential proton
      coupled electron transfer (PCET) steps. Optical titrations along with DFT
      calculations support that the reduced complexes formed in the first step are more
      powerful oxidants than the parent O complexes. These mechanistic insights aid in
      understanding the phenol to bis-phenol reactivity exhibited by 2b and 3b.

PMID- 19119847
TI  - Phenolic compounds rutin and o-coumaric acid ameliorate obesity induced by high
      fat diet in rats.
AB  - Dietary fat is one of the most important environmental factors associated with
      the incidence of cardiovascular diseases. In this study, the antiobesity effects
      of rutin (R) and o-coumaric acid (oCA) were investigated. Wistar rats were
      divided into normal and obese groups, and obese rats were prefed a high-fat diet
      (HFD) containing 40% beef tallow for 4 weeks. Then, R and oCA were given as a
      supplement to obese rats at doses of 50 and 100 mg/kg, respectively, for a period
      of 8 weeks. The results showed that body, liver organ, and adipose tissue weights
      of peritoneal and epididymal fat pads in the HFD+ R and HFD+oCA groups were
      significantly decreased as compared to those in the HFD group. Serum lipid
      profiles, insulin, and leptin were significantly decreased in the HFD+ R (high
      dose, HD) and HFD+oCA (HD) groups as compared to those in the HFD group. Hepatic
      triacylglycerol and cholesterol levels were significantly decreased in the HFD+ R
      (HD) and HFD+oCA (HD) groups as compared to those in the HFD group. Moreover, the
      consumption of R and oCA reduced oxidative stress and glutathione disulfide
      (GSSG) content, and enhanced the levels of glutathione (GSH), GSH peroxidase
      (GPx), GSH reductase (GRd), and GSH S-transferase (GST) in the hepatic tissue of
      rats with HFD-induced obesity. These results demonstrate that intake of R and oCA
      can be beneficial for the suppression of high-fat-diet-induced dyslipidemia,
      hepatosteatosis, and oxidative stress in rats.

PMID- 19119849
TI  - S-Nitrosoglutathione inactivation of the mitochondrial and cytosolic BCAT
      proteins: S-nitrosation and S-thiolation.
AB  - Specific proteins with reactive thiol(ate) groups are susceptible to nitric oxide
      (NO) modification, which can result in S-nitrosation, S-thiolation, or disulfide
      bond formation. In the present study the effect of NO modification on the
      functionality of human mitochondrial and cytosolic branched-chain
      aminotransferases (hBCATm and hBCATc, respectively) was investigated. Here, the
      NO reactive agents, S-nitrosoglutathione (GSNO), S-nitroso-N-acetyl-dl
      penacillamine, and sodium nitroprusside, inactivated both isoforms in a dose
      dependent manner. Furthermore, low concentrations of GSNO caused a time-dependent
      loss in BCAT activity (50 +/- 3% and 77 +/- 2% for hBCATc and hBCATm,
      respectively) correlating with the loss of four and one to two thiol groups,
      respectively, confirming the thiols as targets for NO modification. Analysis of
      GSNO-modified hBCATc by quadrupole time-of-flight mass spectrometry identified a
      major peak containing three NO adducts and a minor peak equivalent to two NO
      adducts and one glutathione (GSH) molecule, the latter confirmed by Western blot
      analysis. Moreover, prolonged exposure or increased levels of GSNO caused
      increased S-glutathionylation and partial dimerization of hBCATc, suggesting a
      possible shift from regulation by NO to one of adaptation during nitrosated
      stress. Although GSNO inactivated hBCATm, neither S-nitrosation, S
      glutathionylation, nor dimerization could be detected, suggesting differential
      mechanisms of regulation through NO between isoforms in the mitochondria and
      cytosol. Reversal of GSNO-modified hBCAT using GSH alone was only partial, and
      complete reactivation was only possible using the glutaredoxin/GSH system (97 +/-
      4% and 91 +/- 3% for hBCATc and hBCATm, respectively), implicating the importance
      of a full physiological redox system for activation/inactivation. To conclude,
      these results clearly demonstrate distinct functional/mechanistic responses to
      GSNO modification between BCAT isoforms and offer intriguing comparisons between
      the BCAT proteins and the respective cytosolic and mitochondrial hTrx and hGrx
      proteins.

PMID- 19119848
TI  - Single-step high-yield radiosynthesis and evaluation of a sensitive 18F-labeled
      ligand for imaging brain peripheral benzodiazepine receptors with PET.
AB  - Elevated levels of peripheral benzodiazepine receptors (PBR) are associated with
      activated microglia in their response to inflammation. Hence, PBR imaging in vivo
      is valuable for investigating brain inflammatory conditions. Sensitive, easily
      prepared, and readily available radioligands for imaging with positron emission
      tomography (PET) are desirable for this purpose. We describe a new 18F-labeled
      PBR radioligand, namely [18F]N-fluoroacetyl-N-(2,5-dimethoxybenzyl)-2
      phenoxyaniline ([18F]9). [18F]9 was produced easily through a single and highly
      efficient step, the reaction of [18F]fluoride ion with the corresponding bromo
      precursor, 8. Ligand 9 exhibited high affinity for PBR in vitro. PET showed that
      [18F]9 was avidly taken into monkey brain and gave a high ratio of PBR-specific
      to nonspecific binding. [18F]9 was devoid of defluorination in rat and monkey and
      gave predominantly polar radiometabolite(s). In rat, a low level radiometabolite
      of intermediate lipophilicity was identified as [18F]2-fluoro-N-(2
      phenoxyphenyl)acetamide ([18F]11). [18F]9 is a promising radioligand for future
      imaging of PBR in living human brain.

PMID- 19119851
TI  - Effect of charge distribution in a flexible loop on the bioluminescence color of
      firefly luciferases.
AB  - Firefly luciferase is a monooxygenase that catalyzes the ATP-dependent conversion
      of firefly luciferin into a luciferyl-adenylate, which is oxidized to an
      electronically excited oxyluciferin in a multistep reaction and produces visible
      light with a remarkable quantum yield. The bioluminescence color of firefly
      luciferases is determined by the luciferase structure and assay conditions. Among
      different beetles, only luciferase from Phrixotrix railroad worm (Ph(RE)) emits
      red bioluminescence, naturally. The presence of Arg353 in Ph(RE) luciferase,
      which corresponds to the deleted residue in the other luciferases, is an
      important distinctive structural feature of it. Insertion of Arg356 into a green
      emitter luciferase (Lampyris turkestanicus), corresponding to Arg353 in
      Phrixotrix hirtus, changed the emitted light from green to red. To further
      clarify the effect of this position on the light shift mechanism, four residues
      with similar sizes but different charges (Arg, Lys, Glu, and Gln) were inserted
      into Photinus pyralis luciferase, using site-specific insertion mutagenesis.
      Insertion of a residue with a positive side chain (Arg356 and Lys356) changed the
      light color to red, while insertion of a residue with a negative side chain
      (Glu356) had little effect on color. Insertion of a neutral residue (Gln356) at
      this position was performed without any change in bioluminescence spectra.
      Insertion of positively charged residues in this loop took place with a series of
      structural changes which were confirmed by fluorescence spectroscopy and homology
      modeling. Homology modeling reveals the appearance of a bulge in a flexible loop
      (T352-P359) upon mutation which shifts to the left side with a color change from
      green to red.

PMID- 19119850
TI  - In vitro kinetic analysis of substrate specificity in enterobactin biosynthetic
      lower pathway enzymes provides insight into the biochemical function of the hot
      dog-fold thioesterase EntH.
AB  - The Escherichia coli siderophore enterobactin is assembled from 2,3
      dihydroxybenzoate (2,3-DHB) and l-serine by the nonribosomal peptide synthetases
      EntB and EntF. The processive thiol-template strategy used can be sabotaged by
      EntB misacylation. Through in vitro kinetic analysis, we demonstrate two
      potential routes to EntB misacylation and provide evidence for two mechanisms by
      which the hot dog-fold thioesterase EntH can potentially prevent or reverse EntB
      misacylation.

PMID- 19119852
TI  - PEGylation of Val-1(alpha) destabilizes the tetrameric structure of hemoglobin.
AB  - A hexaPEGylated hemoglobin (Hb), (Propyl-PEG5K)(6)-Hb, is essentially in
      alphabeta dimers (Hu et al. (2007) Biochem. J. 402, 143-151). In order to provide
      a biochemical insight into the tetramer-dimer dissociation of this PEGylated Hb,
      we prepared and characterized two PEGylated Hbs site-specifically modified at Val
      1(alpha) and at Val-1(beta), respectively. PEGylation at Val-1(alpha) and at Val
      1(beta) increase the tetramer-dimer dissociation constant (K(d)) of Hb by 2 and 1
      order of magnitude, respectively. Accordingly, the sites of PEGylation can
      determine the tetramer stability of the PEGylated Hb. In order to determine the
      role of the polyethylene glycol (PEG) chains on the tetramer stability of Hb, we
      prepared a propylated Hb site-specifically modified at Val-1(alpha).
      Interestingly, site-specific propylation of Hb at Val-l(alpha) stabilizes the Hb
      tetramer by 1 order of magnitude. Therefore, conjugation of the PEG chains at Val
      1(alpha) can greatly destabilize the tetramer stability of Hb. On the structural
      aspects, the PEG chains conjugated at Va-1(alpha) unfavorably alter the heme
      environment and quaternary structure and destabilize the alpha1beta2 interface of
      Hb. On the functional aspects, the PEG chains conjugated at Val-1(alpha) decrease
      the Hill coefficient, the Bohr effect of Hb and the sensitization to the presence
      of the allosteric effectors. In contrast, PEGylation of Hb at Val-1(beta) gives
      rise to less pronounced structural alteration and different functional change.

PMID- 19119853
TI  - Use of the fused NS4A peptide-NS3 protease domain to study the importance of the
      helicase domain for protease inhibitor binding to hepatitis C virus NS3-NS4A.
AB  - The NS3 protein of hepatitis C virus is unusual because it encodes two unrelated
      enzymatic activities in linked protease and helicase domains. It has also been
      intensively studied because inhibitors targeting its protease domain have
      potential to significantly improve treatment options for those infected with this
      virus. Many enzymological studies and inhibitor discovery programs have been
      carried out using the isolated protease domain in complex with a peptide derived
      from NS4A which stimulates activity. However, some recent publications have
      suggested that the NS3 helicase domain may influence inhibitor binding and thus
      suggest work should focus on the full-length NS3-NS4A protein. Here we present
      the characterization of a single-chain protease in which the NS4A peptide
      activator is linked to the N-terminus of the NS3 protease domain. This protein
      behaves well in solution, and its protease activity is very similar to that of
      full-length NS3-NS4A. We find that this fusion protein, as well as the
      noncovalent complex of the NS4A peptide with NS3, gives similar Ki values,
      spanning 3 orders of magnitude, for a set of 25 structurally diverse inhibitors.
      We also show that simultaneous mutation of three residues on the surface of the
      helicase domain which has been hypothesized to interact with the protease does
      not significantly affect enzymatic activity or inhibitor binding. Thus, the
      protease domain with the NS4A peptide, in a covalent or noncovalent complex, is a
      good model for the protease activity of native NS3-NS4A.

PMID- 19119855
TI  - LNA-modified primers drastically improve hybridization to target RNA and reverse
      transcription.
AB  - Knowledge about the structure of RNA is crucial to understanding its biological
      activities. Very often, the presence of unusually thermodynamically stable
      structural fragments in RNAs, such as hairpins, makes it impossible to apply
      primer extension to visualize the results of chemical mapping experiments.
      However, replacement of DNA primers with LNA-modified primers overcomes this
      limitation. This approach was tested successfully on regulatory OxyS RNA and DsrA
      RNA from Escherichia coli.

PMID- 19119856
TI  - Helicobacter pylori NikR's interaction with DNA: a two-tiered mode of
      recognition.
AB  - HPNikR is a prokaryotic nickel binding transcription factor found in the virulent
      bacterium Helicobacter pylori. HPNikR regulates the expression of multiple genes
      as an activator or repressor, including those involved in nickel ion homeostasis,
      acid adaptation, and iron uptake. The target operator sequences of the genes
      regulated by HPNikR do not contain identifiable symmetrical recognition sites,
      and the mechanism by which HPNikR distinguishes between the genes it regulates is
      not understood. Using competitive fluorescence anisotropy (FA) and
      electrophoretic gel mobility shift (EMSA) assays, the interactions between HPNikR
      and the target operator sequences of the genes directly regulated (ureA, NixA,
      NikR, Fur OPI, Fur OPII, Frpb4, FecA3, and exbB) were characterized. These
      studies revealed that HPNikR utilizes a two-tiered mode of DNA recognition by
      binding to some genes with high affinity and others with low affinity. The genes
      that are tightly regulated by HPNikR encode proteins that utilize nickel, while
      those that are less tightly regulated encode other types of proteins. The
      affinities of low-affinity metal ions for a second metal binding site were
      determined to be in the micromolar regime, and a contribution of electrostatics
      to the HPNikR-DNA binding event was determined. Detailed studies of the role of
      sequence length and identity for the interaction between HPNikR and ureA revealed
      a specific length requirement for DNA binding.

PMID- 19119857
TI  - Structural selection of a native fold by peptide recognition. Insights into the
      thioredoxin folding mechanism.
AB  - Thioredoxins (TRXs) are monomeric alpha/beta proteins with a fold characterized
      by a central twisted beta-sheet surrounded by alpha-helical elements. The
      interaction of the C-terminal alpha-helix 5 of TRX against the remainder of the
      protein involves a close packing of hydrophobic surfaces, offering the
      opportunity of studying a fine-tuned molecular recognition phenomenon with long
      range consequences on the acquisition of tertiary structure. In this work, we
      focus on the significance of interactions involving residues L94, L99, E101,
      F102, L103 and L107 on the formation of the noncovalent complex between reduced
      TRX1-93 and TRX94-108. The conformational status of the system was assessed
      experimentally by circular dichroism, intrinsic fluorescence emission and enzymic
      activity; and theoretically by molecular dynamics simulations (MDS). Alterations
      in tertiary structure of the complexes, resulting as a consequence of site
      specific mutation, were also examined. To distinguish the effect of alanine
      scanning mutagenesis on secondary structure stability, the intrinsic helix
      forming ability of the mutant peptides was monitored experimentally by far-UV CD
      spectroscopy upon the addition of 2,2,2-trifluoroethanol, and also theoretically
      by Monte Carlo conformational search and MDS. This evidence suggests a key role
      of residues L99, F102 and L103 on the stabilization of the secondary structure of
      alpha-helix 5, and on the acquisition of tertiary structure upon complex
      formation. We hypothesize that the transition between a partially folded and a
      native-like conformation of reduced TRX1-93 would fundamentally depend on the
      consolidation of a cooperative tertiary unit based on the interaction between
      alpha-helix 3 and alpha-helix 5.

PMID- 19119858
TI  - Disorder and structure in the Rab11 binding domain of Rab11 family interacting
      protein 2.
AB  - Rab11 plays a central role in plasma membrane recycling which returns cellular
      receptors for reuse at the cell surface. A recently identified family of Rab11
      interacting proteins (FIP) includes FIP2. The C-terminal region of FIP2 is
      essential for colocalization with Rab11 on early endosomes and for enabling
      formation of higher-order oligomers. Rab11 binding and oligomerization of FIP2
      are separable. Here we have determined the three-dimensional structure of the 40
      residue coiled-coil oligomerization domain of FIP2 in the absence of Rab11 using
      NMR methods. The N-terminal half showed strong NOE cross-peaks and well-dispersed
      NMR resonances, whereas the C-terminal half had fewer NOE cross-peaks and less
      chemical shift dispersion. The 10 C-terminal residues were mostly disordered. The
      final structures of the dimer had favorable Ramachandran angles and a root-mean
      square deviation of 0.59 +/- 0.13 A over superimposed backbone residues. The
      structure allows a comparison to a structure of FIP2 in complex with Rab11 that
      was determined crystallographically. In complex with Rab11, the C-terminal
      residues are not disordered but have a helical structure that predicts residual
      dipolar coupling constants that are incompatible with those measured on the
      unbound FIP2. In both structures, a histidine residue is found at the normally
      hydrophobic position of the heptad repeat of the coiled coil, and here we show
      its ionization destabilizes the coiled-coil structure. Together, these data allow
      us to build a model in which the binding of FIP family proteins to Rab11 can be
      described in terms of conformational changes and that suggests new modes of
      regulation.

PMID- 19119859
TI  - Cautionary tales of the unexpected.

PMID- 19119860
TI  - Engineered repeated electromagnetic field shock therapy for cellular senescence
      and age-related diseases.
AB  - A new consensus of gerontologists proposes that delay of biological senescence is
      the most potent public health measure for preventing chronic disease in late
      life. At the most fundamental level, cellular aging is characterized by a decline
      in repair and homeostatic systems. Thus, interventions that protect or rejuvenate
      these cellular systems hold significant promise for preventing or delaying the
      onset of age-related diseases. The most likely candidates for delaying senescence
      are the longevity-linked transcription factors DAF16 and HSF1. If one were to
      engineer negligible senescence, a key target would be the heat shock protein axis
      regulated by HSF1. This pathway is the preferred pathway to prevent protein
      damage or aggregation, whereas DAF-16/FOXO is a backup pathway activated during
      stress. Reduced HSF1 activity appears to accelerate tissue aging and shortens
      life span. Conversely, over-expression of HSF1 increases life span and decreases
      amyloid toxicity in animal models. This paper describes enhancement of the
      HSR/HSF1 pathway engineered by repeated electromagnetic field shock (REMFS). In a
      recent study, we demonstrated that REMFS therapy upregulates the HSR/HSF1
      pathway, delays cellular senescence in young cells, and transiently reverses it
      in senescent cells, thus altering cellular mortality. The technology of applying
      certain beneficial EMF energy to the human body to stimulate the natural stress
      response and activate the repair and maintenance systems is a new strategy for
      engineered negligible senescence. We discuss the exciting clinical implications
      of REMFS therapy in human aging and disease.

PMID- 19119861
TI  - Consolidating the mission to defeat aging: a big step forward.

PMID- 19119862
TI  - The Hyper-Commons: how open science prizes can expand and level the medical
      research playing field.
AB  - The largest industry in America is increasingly incapable of serving its
      customers. Over-fencing of the information commons has led to unaffordable
      medicine, for want of which millions of Americans and people around the world go
      without lifesaving treatments. Eliminating patent distribution exclusivity
      altogether, however, is not feasible, given the entrenched nature of the health
      care industry. This paper proposes a program of voluntary Open Science Prizes
      that would draw large numbers of new players, who would in turn produce much new
      medical innovation, provide academic priority recognition, and develop a growing
      body of patent-beating prior art that would serve as public domain firewalls on a
      new supranational Hyper-Commons.

PMID- 19119864
TI  - Interview with Kevin Warwick, D.Sc. Interview by Vicki Glaser.

PMID- 19119865
TI  - Supercentenarians Table: validated supercentenarian cases aged 114 and above.

PMID- 19119868
TI  - Atomic-scale, all epitaxial in-plane gated donor quantum dot in silicon.
AB  - Nanoscale control of doping profiles in semiconductor devices is becoming of
      critical importance as channel length and pitch in metal oxide semiconductor
      field effect transistors (MOSFETs) continue to shrink toward a few nanometers.
      Scanning tunneling microscope (STM) directed self-assembly of dopants is
      currently the only proven method for fabricating atomically precise electronic
      devices in silicon. To date this technology has realized individual components of
      a complete device with a major obstacle being the ability to electrically gate
      devices. Here we demonstrate a fully functional multiterminal quantum dot device
      with integrated donor based in-plane gates epitaxially assembled on a single
      atomic plane of a silicon (001) surface. We show that such in-plane regions of
      highly doped silicon can be used to gate nanostructures resulting in highly
      stable Coulomb blockade (CB) oscillations in a donor-based quantum dot. In
      particular, we compare the use of these all epitaxial in-plane gates with
      conventional surface gates and find superior stability of the former. These
      results show that in the absence of the randomizing influences of interface and
      surface defects the electronic stability of dots in silicon can be comparable or
      better than that of quantum dots defined in other material systems. We anticipate
      our experiments will open the door for controlled scaling of silicon devices
      toward the single donor limit.

PMID- 19119867
TI  - Synthesis, characterization, and in vitro antimalarial and antitumor activity of
      new ruthenium(II) complexes of chloroquine.
AB  - The new Ru(II) chloroquine complexes [Ru(eta(6)-arene)(CQ)Cl2] (CQ = chloroquine;
      arene = p-cymene 1, benzene 2), [Ru(eta(6)-p-cymene)(CQ)(H2O)2][BF4]2 (3),
      [Ru(eta(6)-p-cymene)(CQ)(en)][PF6]2 (en = ethylenediamine) (4), and [Ru(eta(6)-p
      cymene)(eta(6)-CQDP)][BF4]2 (5, CQDP = chloroquine diphosphate) have been
      synthesized and characterized by use of a combination of NMR and FTIR
      spectroscopy with DFT calculations. Each complex is formed as a single
      coordination isomer: In 1-4, chloroquine binds to ruthenium in the eta(1)-N mode
      through the quinoline nitrogen atom, whereas in 5 an unprecedented eta(6) bonding
      through the carbocyclic ring is observed. 1, 2, 3, and 5 are active against CQ
      resistant (Dd2, K1, and W2) and CQ-sensitive (FcB1, PFB, F32, and 3D7) malaria
      parasites (Plasmodium falciparum); importantly, the potency of these complexes
      against resistant parasites is consistently higher than that of the standard drug
      chloroquine diphosphate. 1 and 5 also inhibit the growth of colon cancer cells,
      independently of the p53 status and of liposarcoma tumor cell lines with the
      latter showing increased sensitivity, especially to 1 (IC50 8 microM); this is
      significant because this type of tumor does not respond to currently employed
      chemotherapies.

PMID- 19119869
TI  - Active molecular plasmonics: controlling plasmon resonances with molecular
      switches.
AB  - A gold nanodisk array, coated with bistable, redox-controllable [2]rotaxane
      molecules, when exposed to chemical oxidants and reductants, undergoes switching
      of its plasmonic properties reversibly. By contrast, (i) bare gold nanodisks and
      (ii) disks coated with a redox-active, but mechanically inert, control compound
      do not display surface-plasmon-based switching. Along with calculations based on
      time-dependent density functional theory, these experimental observations suggest
      that the nanoscale movements within surface-bound "molecular machines" can be
      used as the active components in plasmonic devices.

PMID- 19119870
TI  - Mononuclear metallacyclic silver(I) complexes of third generation bis(1
      pyrazolyl)methane ligands.
AB  - The third-generation bis(1-pyrazolyl)methane ligands p
      C(6)H(4)[CH(2)OCH(2)CH(pz)(2)](2) (L(p), pz = pyrazolyl ring) and m
      C(6)H(4)[CH(2)OCH(2)CH(pz)(2)](2) (L(m)) have been synthesized by the reaction of
      (pz)(2)CHCH(2)OH with NaH followed by alpha,alpha'-dibromo-p-xylene or
      alpha,alpha'-dibromo-m-xylene. The reaction of L(p) with AgBF(4), AgPF(6), and
      AgO(3)SCF(3) yields the new compounds {Ag[p
      C(6)H(4)(CH(2)OCH(2)CH(pz)(2))(2)]}BF(4), {Ag[p
      C(6)H(4)(CH(2)OCH(2)CH(pz)(2))(2)]}PF(6), and {Ag[p
      C(6)H(4)(CH(2)OCH(2)CH(pz)(2))(2)]}O(3)SCF(3), respectively. A similar reaction
      of L(m) with AgBF(4) and AgPF(6) yields {Ag[m
      C(6)H(4)(CH(2)OCH(2)CH(pz)(2))(2)]}BF(4) and {Ag[m
      C(6)H(4)(CH(2)OCH(2)CH(pz)(2))(2)]}PF(6). These compounds were crystallized from
      both acetone and acetonitrile to yield nine crystalline forms of (LAg)(+) that
      differ in counterion and solvent of crystallization. In all complexes, the four
      pyrazolyl rings of the ligand chelate a single silver(I) cation in a distorted
      tetrahedral environment to form mononuclear metallacycles. This arrangement has
      not previously been observed with the analogous ligands based on tris(1
      pyrazolyl)methane units and is unique because of the ring sizes (16-member rings
      in L(m) and 17-member rings in L(p)). The dominant feature in all of these solid
      state structures, regardless of solvent or anion, is this cationic metallacyclic
      architecture, which does not readily lend itself to strong supramolecular
      organization.

PMID- 19119871
TI  - Influence of synthetic polyelectrolytes on the growth and properties of
      hyaluronan-chitosan multilayers.
AB  - Both hyaluronan (HA) and chitosan (CHI) are biocompatible polysaccharide
      electrolytes. The multilayers formed by these polyelectrolytes alone are known to
      be rather soft and strongly viscoelastic. In this work we study multilayers
      formed by incorporating synthetic nonsaccharide polyelectrolytes such as
      polyallylamine (PAH) and poly(acrylic acid) (PAA) in various proportions into the
      HA/CHI layers. The buildup was followed on a quartz crystal resonator. Surface
      acoustic impedance recorded in these measurements, in suitable conditions, gives
      a spiral when plotted in the complex plane. The shape of this spiral depends on
      the viscoelasticity of the layer material and regularity of the growth process.
      We found that poly(acrylic acid) destroys the soft diffuse matrix formed by
      hyaluronan. It forms diffusion barriers when deposited sparsely between the
      layers. If its proportion is higher, the film growth adopts a linear buildup in
      the layer-by-layer process. The linear buildup of CHI/PAA reveals that the
      buildup regime of a multilayer film does not determine the viscoelastic
      properties of the film. Linearly and exponentially growing films may have very
      similar mechanical properties. Polyacrylic acid forms a kind of scaffold inside
      the film giving the natively soft hyaluronan/chitosan film more mechanical
      strength. The optimal combination gave more than 100-fold increase in the shear
      modulus.

PMID- 19119872
TI  - Orientated Langmuir-Blodgett assembly of VO(2) nanowires.
AB  - We report Langmuir-Blodgett (LB) based assembly of vanadium dioxide (VO(2))
      nanowires. VO(2) nanowires were functionalized with stearic acid (SA) and
      cetyltrimethylammonium bromide (CTAB) and then spread on the surface in an
      aqueous phase in a LB trough. Surface pressure-area (pi-A) isotherms were
      recorded on the LB trough and show hysteretic behavior. Scanning electron
      microscopy investigations of morphology and alignment of the VO(2) nanowire films
      transferred at different points on the pi-A curve demonstrate that with
      increasing surface pressure there is a transition from well-separated domains of
      nanowires to compact and locally ordered nanowire monolayers, while aggregates of
      raftlike nanowire structures remain after expansion. Interestingly, X-ray
      diffraction studies show that VO(2) nanowire LB films exhibit (00l) crystal plane
      orientation, which is attributed to preferential coordination of SA and CTAB-SA
      complex to (001) surface of VO(2) nanowires thereby driving this orientation.

PMID- 19119873
TI  - A rapid, asymmetric synthesis of the decahydrofluorene core of the hirsutellones.
AB  - A tandem ketene-trapping/Diels-Alder cyclization sequence was the pivotal
      transformation in an efficient, asymmetric synthesis of a decahydrofluorene
      tricyclic structure possessing eight stereogenic centers and key features of the
      hirsutellone class of antitubercular natural products. The hirsutellone-like beta
      keto ester that was fashioned by this sequence (13 steps; 6% overall yield)
      demonstrated significant inhibitory activity against Mycobacterium tuberculosis.
      The mechanism of action of this antitubercular compound is not yet known.

PMID- 19119876
TI  - The coevolving web of life.
AB  - Coevolution--reciprocal evolutionary change in interacting species--is one of the
      central biological processes organizing the web of life, and most species are
      involved in one or more coevolved interactions. We have learned in recent years
      that coevolution is a highly dynamic process that continually reshapes
      interactions among species across ecosystems, creating geographic mosaics over
      timescales sometimes as short as thousands or even hundreds of years. If we take
      that as our starting point, what should we now be asking about the coevolutionary
      process? Here I suggest five major questions that we need to answer if we are to
      understand how coevolution shapes the web of life. How evolutionarily dynamic is
      specialization to other species, and what is the role of coevolutionary
      alternation in driving those dynamics? Does the geographic mosaic of coevolution
      shape adaptation in fundamentally different ways in different forms of
      interaction? How does the geographic mosaic of coevolution shape speciation? How
      does the structure of reciprocal selection change during the assembly of large
      webs of interacting species? How important are genomic events such as whole
      genome duplication (i.e., polyploidy) and whole-genome capture (i.e.,
      hybridization) in generating novel webs of interacting species? I end by
      suggesting four points about coevolution that we should tell every new student or
      researcher in biology.

PMID- 19119875
TI  - Reaction mechanism of the epsilon subunit of E. coli DNA polymerase III: insights
      into active site metal coordination and catalytically significant residues.
AB  - The 28 kDa epsilon subunit of Escherichia coli DNA polymerase III is the
      exonucleotidic proofreader responsible for editing polymerase insertion errors.
      Here, we study the mechanism by which epsilon carries out the exonuclease
      activity. We performed quantum mechanics/molecular mechanics calculations on the
      N-terminal domain containing the exonuclease activity. Both the free-epsilon and
      a complex epsilon bound to a theta homologue (HOT) were studied. For the epsilon
      HOT complex Mg(2+) or Mn(2+) were investigated as the essential divalent metal
      cofactors, while only Mg(2+) was used for free-epsilon. In all calculations a
      water molecule bound to the catalytic metal acts as the nucleophile for
      hydrolysis of the phosphate bond. Initially, a direct proton transfer to H162 is
      observed. Subsequently, the nucleophilic attack takes place followed by a second
      proton transfer to E14. Our results show that the reaction catalyzed with Mn(2+)
      is faster than that with Mg(2+), in agreement with experiment. In addition, the
      epsilon-HOT complex shows a slightly lower energy barrier compared to free
      epsilon. In all cases the catalytic metal is observed to be pentacoordinated.
      Charge and frontier orbital analyses suggest that charge transfer may stabilize
      the pentacoordination. Energy decomposition analysis to study the contribution of
      each residue to catalysis suggests that there are several important residues.
      Among these, H98, D103, D129, and D146 have been implicated in catalysis by
      mutagenesis studies. Some of these residues were found to be structurally
      conserved on human TREX1, the exonuclease domains from E. coli DNA-Pol I, and the
      DNA polymerase of bacteriophage RB69.

PMID- 19119877
TI  - Outcomes and complications of direct end-to-side facial-hypoglossal nerve
      anastomosis according to the modified May technique.
AB  - OBJECT: The aim of this study was to address the efficiency and safety of direct
      end-to-side facial-hypoglossal nerve anastomosis for facial palsy rehabilitation.
      METHODS: The authors conducted a retrospective study of 12 consecutive procedures
      performed between December 2000 and February 2006. Facial palsies were caused by
      the surgical removal of tumors in the brainstem, cerebellopontine angle, or
      mastoid process. Direct end-to-side facial-hypoglossal anastomosis was performed
      in each case. Facial function (evaluated using the overall percentage of facial
      function and House-Brackmann scale grades), as well as tongue trophicity and
      mobility, were assessed at 6, 12, and 24 months after surgery. Postoperative
      early and late complications were systematically reviewed. RESULTS: The mean
      delay between tumoral and reparative surgery was 15.9 +/- 4 months (median 11
      months). Preoperatively, the mean percentage facial function score was 11.6 +/-
      1.7% (45% of patients with House-Brackmann Grade 5 facial palsy and 55% of
      patients with House-Brackmann Grade 6). Mean facial function scores increased to
      19.3, 32.2, and 43.8% at 6, 12, and 24 months after surgery, respectively. Twenty
      four months after surgery, 50% of cases had House-Brackmann Grade 3 facial palsy
      and 50% had Grade 4. A significantly better recovery at 24 months was observed
      postoperatively for neural lesions occurring in the mastoid or the brainstem
      compared with those in the cerebellopontine angle. Tongue hemiparesis was
      observed in 5 patients (41.7%), 2 of whom had tongue hypotrophy (16.7%). No
      patient complained of swallowing or speech disturbance. Facial synkinesis was
      noted in 1 patient (8.3%). CONCLUSIONS: Facial recovery after direct end-to-side
      facial-hypoglossal nerve anastomosis is similar to results observed with end-to
      end or end-to-side facial-hypoglossal nerve anastomosis with an interpositional
      graft. Tongue hypotrophy and palsy were observed in a small number of cases. This
      procedure allows one to minimize, although not fully prevent, facial synkinesis.
      The site of the neural lesion appears to be an important factor in the prognosis
      of recovery.

PMID- 19119878
TI  - Prevention of cerebral vasospasm by local delivery of cromakalim with a
      biodegradable controlled-release system in a rat model of subarachnoid
      hemorrhage.
AB  - OBJECT: One mechanism that contributes to cerebral vasospasm is the impairment of
      potassium channels in vascular smooth muscles. Adenosine triphosphate-sensitive
      potassium channel openers (PCOs) appear to be particularly effective for dilating
      cerebral arteries in experimental models of subarachnoid hemorrhage (SAH). A mode
      of safe administration that provides timed release of PCO drugs is still a
      subject of investigation. The authors tested the efficacy of locally delivered
      intrathecal cromakalim, a PCO, incorporated into a controlled-release system to
      prevent cerebral vasospasm in a rat model of SAH. METHODS: Cromakalim was coupled
      to a viscous carrier, hyaluronan, 15% by weight. In vitro release kinetics
      studies showed a steady release of cromakalim over days. Fifty adult male Sprague
      Dawley rats weighing 350-400 g each were divided into 10 groups and treated with
      various doses of cromakalim or cromakalim/hyaluronan in a rat double SAH model.
      Treatment was started 30 minutes after the second SAH induction. Animals were
      killed 3 days after treatment, and the basilar arteries were processed for
      morphometric measurements and histological analysis. RESULTS: Controlled release
      of cromakalim from the cromakalim/hyaluronan implant at a dose of 0.055 mg/kg
      significantly increased lumen patency in a dose-dependent manner up to 94 +/- 8%
      (mean +/- standard error of the mean) of the basilar arteries of the sham group
      compared with the empty polymer group (p = 0.006). Results in the empty polymer
      group were not different from those in the SAH-only group, with a lumen patency
      of 65 +/- 12%. Lumen patencies of the cromakalim-only groups did not differ in
      statistical significance at low (64 +/- 9%) or high (66 +/- 7%) doses compared to
      the SAH-only group. CONCLUSIONS: Treatment of SAH with a controlled-release
      cromakalim/hyaluronan implant prevented experimental cerebral vasospasm in this
      rat double hemorrhage model; this inhibition was dose-dependent. The authors'
      results confirm that sustained delivery of cromakalim perivascularly to cerebral
      vessels could be an effective therapeutic strategy in the treatment of cerebral
      vasospasm after SAH.

PMID- 19119879
TI  - ABC Surgical Risk Scale for skull base meningioma: a new scoring system for
      predicting the extent of tumor removal and neurological outcome. Clinical
      article.
AB  - OBJECT: Surgery for skull base meningiomas (SBMs) can lead to complications
      because these lesions are difficult to approach and can involve cranial nerves
      and arteries. The authors propose a scoring system to evaluate the relative risks
      and benefits of surgical treatment of SBMs. METHODS: The authors used a 2-step
      process to construct their scale. First, they derived significant predictive
      variables from retrospective data on 132 SBM cases treated surgically (primary
      surgeries only) between May 2000 and December 2005. Next, they validated the
      predictive accuracy of their scoring system in 60 consecutive cases treated
      surgically between January 1995 and April 2000, including both primary and
      repeated surgeries. Finally, they investigated the effect of the surgery on the
      patients' preoperative symptoms for consecutive cases treated surgically between
      January 1995 and December 2005, including both primary surgeries and
      retreatments. RESULTS: Five items that predicted surgical risk were identified:
      1) tumor attachment size; 2) arterial involvement; 3) brainstem contact; 4)
      central cavity location; and 5) cranial nerve group involvement. The authors
      named their scoring system the ABC Surgical Risk Scale, after the initial letters
      of these items. Each factor was assigned a score of 0-2 points, and an additional
      point was added for previous surgical treatment or for radiation, giving a
      possible total score of 12 points. On average, the scoring system allocated 2
      points for gross-total resections, 6.1 points for near-total resections, and 9
      points for subtotal resections, with significant differences between groups. For
      cases scoring >or= 8 points, the percentage of cases showing neurological
      deterioration postoperatively exceeded the percentage showing improvement.
      CONCLUSIONS: The authors conclude that this scoring system can be used to predict
      the extent of tumor removal and that the scores reflect the surgical risk.

PMID- 19119880
TI  - Memory outcome following transsylvian selective amygdalohippocampectomy in 62
      patients with hippocampal sclerosis.
AB  - OBJECT: It remains unclear whether selective amygdalohippocampectomy, an
      operative technique developed for use in epilepsy surgery to spare unaffected
      brain tissue and thus minimize the cognitive consequences of temporal lobe
      surgery, actually leads to a better memory outcome. The present study was
      performed to determine the effects of selective surgery on memory outcome in
      patients with intractable mesial temporal lobe epilepsy due to hippocampal
      sclerosis treated using transsylvian selective amygdalohippocampectomy (TSA).
      METHODS: The study population consisted of 62 patients with left hemisphere
      language dominance who underwent left-(31 patients) or right-sided (31 patients)
      TSA. All patients underwent comprehensive neuropsychological testing before and 1
      month and 1 year after unilateral TSA. Verbal Memory I, Nonverbal Memory I, Total
      Memory, Attention, and Delayed Recall were assessed using the Wechsler Memory
      Scale-Revised, whereas Verbal Memory II was assessed using the Miyake Verbal
      Retention Test (MVRT), and Nonverbal Memory II was assessed using the Benton
      Visual Retention Test. Separate repeated-measures multivariate analysis of
      variance (MANOVA) were performed for these intervals with memory scores. RESULTS:
      The results of MANOVA indicated that patients who underwent right-sided TSA
      showed significant improvements in Verbal Memory I (preoperatively vs 1 month
      postoperatively, p < 0.0001; and preoperatively vs 1 year postoperatively, p =
      0.0002), Nonverbal Memory I (preoperatively vs 1 month postoperatively, p =
      0.0003; and preoperatively vs 1 year postoperatively, p = 0.006), and Delayed
      Recall (preoperatively vs 1 month postoperatively, p = 0.028) at both 1-month and
      1-year follow-ups. In addition, Verbal Memory II (MVRT) was also significantly
      improved 1 year after surgery (p = 0.001). In the group of patients who underwent
      left-sided TSA, both Verbal Memory I and II were maintained at the same level 1
      month after surgery, whereas the Verbal Memory I score 1 year after surgery
      increased with marginal significance (p = 0.074). In addition, Verbal Memory II
      showed significant improvement 1 year after surgery (p = 0.049). There were no
      significant changes in Nonverbal Memory I and II, Attention, or Delayed Recall at
      either the 1-month or 1-year follow-up. CONCLUSIONS: Results of the present study
      indicated that left-sided TSA for hippocampal sclerosis tends to improve verbal
      memory function with the preservation of other types of memory function.
      Moreover, right-sided TSA for hippocampal sclerosis can lead to significant
      improvement in memory function, with memory improvement observed 1 month after
      right-sided TSA and persisting 1 year after surgery.

PMID- 19119881
TI  - A novel strategy for repairing preganglionic cervical root avulsion in brachial
      plexus injury by sural nerve grafting.
AB  - OBJECT: In this study, the authors evaluated the efficacy of a new surgical
      strategy for reconnecting the injured brachial plexus with the spinal cord using
      fibrin glue containing acidic fibroblast growth factor as an adhesive and
      neurotrophic agent. METHODS: Eighteen patients with preganglionic brachial plexus
      injuries, each with varying degrees of upper limb dysfunction, underwent cervical
      laminectomy with or without sural nerve grafting. The treatment of each avulsed
      root varied according to the severity of the injury. Some patients also underwent
      a second-stage operation involving supraclavicular brachial plexus exploration
      for reconnection with the corresponding segment of cervical spinal cord at the
      trunk level. Muscle strength was graded both pre- and postoperatively with the
      British Medical Research Council scale, and the results were analyzed with the
      Friedman and Wilcoxon signed-rank tests. RESULTS: Muscle strength improvements
      were observed in 16 of the 18 patients after 24 months of follow-up. Significant
      improvements in mean muscle strength were observed in patients from all repair
      method groups at 12 and 24 months postoperatively (p < 0.05). Statistical
      significance was not reached in the groups with insufficient numbers of cases.
      CONCLUSIONS: The authors' new surgical strategy yielded clinical improvement in
      muscle strength after preganglionic brachial plexus injury, such that nerve
      regeneration may have taken place. Reconnection of the brachial plexus to the
      cervical spinal cord is possible. Functional motor recovery, observed through
      increases in Medical Research Council-rated muscle strength in the affected arm,
      is likewise possible.

PMID- 19119882
TI  - Clip versus coil.

PMID- 19119883
TI  - Collagen matrix duraplasty.

PMID- 19119884
TI  - Ventriculostomy catheter placement.

PMID- 19119885
TI  - Posterior inferior cerebellar artery dissection.

PMID- 19119887
TI  - Introduction: Spinal vascular malformations.
AB  - From the earliest observations of spinal vascular malformations, successful
      management has been challenging. Initially the challenges were diagnosing,
      understanding, and treating these lesions. They were originally considered all to
      be the same, or at least to be a single general type, of disease. With the
      introduction of selective spinal arteriography in the 1960s and more recently
      with the introduction and widespread use of MR imaging, the initial challenge of
      diagnosing spinal vascular malformations was overcome, and significant progress
      has been made in understanding their anatomy as well as the pathophysiology that
      underlies the myelopathy commonly associated with them. The anatomical features
      defined by selective arteriography and the observations permitted with the
      operating microscope ultimately led to distinctions between the major categories
      of the vascular lesions affecting the spinal cord; these distinctions were based
      on the lesions' anatomy, epidemiology, and the mechanism of spinal cord injury.

PMID- 19119888
TI  - Albert Wojciech Adamkiewicz (1850-1921): unsung hero behind the eponymic artery.
AB  - The artery of Adamkiewicz is an important radiculomedullary artery supplying the
      spinal cord, especially the lumbar enlargement. Anatomical knowledge of this
      artery is important for avoiding serious neurological complications during
      surgery performed in this region--for neurosurgeons and interventional
      radiologists treating intramedullary tumors and spinal arteriovenous
      malformations, traumatologists performing spinal fusions, thoracic surgeons
      treating aortic aneurysms, and urologists and pediatric surgeons conducting
      retroperitoneal dissections. However, the biography of the talented Polish
      pathologist Albert Adamkiewicz, after whom the landmark artery is named, has not
      been described adequately in the existing neurosurgical literature. The authors
      bring to light the historical perspective of the eponymic artery and provide a
      recapitulation of other significant contributions made by Adamkiewicz, mostly
      involving the nervous system. His research papers on the histology of neuronal
      tissues and neurodegenerative diseases had high scientific merit, but the
      discovery of the anticancer antitoxin "cancroin" and his postulation of a cancer
      causing parasite he named "Coccidium sarcolytus" met with harsh criticism and
      eventually led to his ill fame. The biography is supplemented with a brief
      overview of the important surgical implications of the artery of Adamkiewicz.

PMID- 19119889
TI  - Type I spinal dural arteriovenous fistulas: historical review and illustrative
      case.
AB  - Type I spinal dural arteriovenous fistulas are the most common vascular
      malformation of the spinal cord, and an important cause of reversible progressive
      myelopathy. This lesion remains underdiagnosed, with most patients presenting
      late in the course of the disease. In this article the authors provide a review
      of the literature with particular attention to historical aspects related to the
      pathophysiology, diagnosis, classification, clinical findings, natural history,
      and treatment of this lesion. An illustrative case is also provided.

PMID- 19119890
TI  - Intracranial subarachnoid hemorrhage resulting from cervical spine dural
      arteriovenous fistulas: literature review and case presentation.
AB  - Cervical dural arteriovenous fistulas (dAVFs) are a rare cause of intracranial
      subarachnoid hemorrhage (SAH) but should be considered when other sources are not
      found. Subarachnoid hemorrhage caused by dAVF is thought to occur as a result of
      venous hypertension in most cases. The clinical presentation, acute onset of
      severe headache, is similar to that in patients with other causes of SAH;
      however, severe neurological deficits (Hunt and Hess Grade IV and V SAH) have not
      been reported in SAH caused by cervical dAVFs. Patients with this type of SAH
      commonly report suboccipital headache, neck pain, and nausea, and thus these
      hemorrhages can be easily dismissed as perimesencephalic SAH. Vigilant evaluation
      with 4-vessel cerebral angiography, including selective catheterization of both
      proximal vertebral arteries, should be performed. The practice of unilateral
      vertebral artery injection with reflux into the contralateral vertebral and
      posterior inferior cerebellar arteries has the potential to overlook cervical
      dAVF. Magnetic resonance imaging may be useful to evaluate for other causes of
      SAH but is probably not sensitive for the identification of a cervical dAVF.
      Surgical treatment of this lesion has an excellent outcome.

PMID- 19119891
TI  - Spinal extradural arteriovenous malformations with parenchymal drainage: venous
      drainage variability and implications in clinical manifestations.
AB  - OBJECT: Although nontraumatic spinal arteriovenous malformations and fistulas
      (AVMs and AVFs) restricted to the epidural space are rare, they can lead to
      significant neurological morbidity. Careful diagnostic imaging is essential to
      their detection and the delineation of the pathological anatomy. Aggressive
      endovascular and open operative treatment can provide arrest and reversal of
      neurological deficits. METHODS: The authors report on 6 cases of extradural
      AVMs/AVFs causing progressive myelopathy. Clinical findings, diagnostic
      evaluation, treatment, and outcome are discussed. Special consideration is given
      to the anatomy of the lesions and the operative techniques used to treat them. A
      review of the literature concerning extradural vascular malformations is also
      presented. RESULTS: All 6 cases of extradural AVMs had an extradural fistulous
      location with intradural medullary venous drainage. These cases illustrate
      progressive myelopathy through cord venous congestion (hypertension) that can be
      caused by an extradural nidus or fistula. In 4 cases, a large epidural lake was
      identified on angiography. At surgery, the epidural lake was obliterated and
      medullary drainage interrupted. All patients had stabilization of their
      neurological deficits and successful obliteration of the AVM/AVF was obtained.
      CONCLUSIONS: Extradural AVMs and AVFs are a poorly described entity with
      published clinical experience limited to sporadic case reports and small series.
      Although these lesions have a purely extradural location of arteriovenous
      shunting and early venous drainage, they can be responsible for acute and
      progressive neurological symptoms similar to those caused by their dural-based
      intradural counterparts. With careful imaging recognition of the pathological
      anatomy, surgical and endovascular techniques can be used for the treatment of
      extradural AVMs affording effective and durable obliteration with stabilization
      or reversal of neurological symptoms. Venous drainage directly correlates the
      pathologic mechanisms of presentation. Specific attention must be paid
      intraoperatively to the epidural lake common to both variants so that recurrence
      is avoided.

PMID- 19119892
TI  - Spinal cord vascular shunts: spinal cord vascular malformations and dural
      arteriovenous fistulas.
AB  - OBJECT: Spinal cord vascular malformations are rare, fascinating lesions. In this
      paper, the authors' goal was to demonstrate how these lesions, more specifically
      spinal cord arteriovenous malformations and dural arteriovenous fistulas, are
      assessed, classified, and managed at their institution. They also highlight some
      aspects of classification and management that may be different from the views of
      others. METHODS: The authors reviewed the 20-year experience at the senior
      author's institution regarding the management of spinal cord vascular
      malformations. They discuss the management, surgical and endovascular treatment
      results, and the classification that resulted from the combined experience of 3
      major reference centers. RESULTS: The accumulated knowledge on embryological and
      pathophysiological aspects in such a rare disease resulted in a more global,
      patient-oriented (and not radiologically oriented) approach to spinal cord
      shunts. CONCLUSIONS: The multiple classifications proposed for spinal cord
      vascular malformations reflect the continuous advancement of the authors'
      understanding. They adopt a classification based on new physiological and genetic
      data that treats these lesions as expressions of more complex disease processes
      and not simply a morphological target, with direct impact on therapeutic options.

PMID- 19119893
TI  - Endovascular management of spinal vascular malformations: history and literature
      review.
AB  - Spinal vascular malformations represent a complex group of entities whose
      treatment paradigm continually evolves. Given the ever-increasing role of
      endovascular therapy, it is the goal of the authors to review the current
      literature regarding this therapeutic tool and to provide recommendations guiding
      management. A thorough literature search was conducted using Medline, with
      subsequent articles being identified through cross-referencing. The analysis
      revealed that, since its introduction in the 1960s, endovascular therapy has been
      used to manage the entire spectrum of spinal vascular malformations, during which
      period it has undergone considerable technological and technical evolution. As
      such, embolization has proved of growing therapeutic utility, largely resulting
      from the mounting evidence supporting its safety and efficacy, in addition to the
      inherent minimally invasive nature. This alternative to surgical intervention
      will be increasingly used as first-line therapy in spinal vascular malformations.

PMID- 19119894
TI  - Overview of the current role of endovascular and surgical treatment in spinal
      dural arteriovenous fistulas.
AB  - Dural arteriovenous fistulas are the most common vascular malformations of the
      spinal cord. These benign vascular lesions are considered straightforward targets
      of surgical treatment and possibly endovascular embolization, but the outcome in
      these cases depends mainly on the extent of clinical dysfunction at the time of
      the diagnosis. A timely diagnosis is an equally important factor, with early
      treatment regardless of the type more likely to yield significant improvements in
      neurological functioning. The outcomes after surgical and endovascular treatment
      are similar if complete obliteration of the fistulous site is obtained. In the
      present study, the authors evaluated the current role of each modality in the
      management of these interesting lesions.

PMID- 19119895
TI  - Advanced noninvasive imaging of spinal vascular malformations.
AB  - Spinal vascular malformations (SVMs) are an uncommon, heterogeneous group of
      vascular anomalies that can render devastating neurological consequences if they
      are not diagnosed and treated in a timely fashion. Imaging SVMs has always
      presented a formidable challenge because their clinical and imaging presentations
      resemble those of neoplasms, demyelination diseases, and infection. Advancements
      in noninvasive imaging modalities (MR and CT angiography) have increased during
      the last decade and have improved the ability to accurately diagnose spinal
      vascular anomalies. In addition, intraoperative imaging techniques have been
      developed that aid in the intraoperative assessment before, during, and after
      resection of these lesions with minimal and/or optimal use of spinal digital
      subtraction angiography. In this report, the authors review recent advancements
      in the imaging of SVMs that will likely lead to more timely diagnoses and
      treatment while reducing procedural risk exposure to the patients who harbor
      these uncommon spinal lesions.

PMID- 19119896
TI  - The pediatric neurosurgical workforce: defining the current supply. Clinical
      article.
AB  - OBJECT: The purpose of this study was to determine a reliable estimate of the
      size, demographic, and practice characteristics of the current pediatric
      neurosurgical workforce. The authors also sought to differentiate pediatric from
      nonpediatric neurosurgical practitioners and compare the demographic and practice
      characteristics of these 2 groups. The term "pediatric practitioner" will be used
      in this study to describe a practitioner whose practice is > 75% pediatric
      patients in accordance with the American Board of Pediatric Neurological Surgery
      (ABPNS) requirements for board certification in pediatric neurosurgery. Those
      practitioners with < 75% pediatric patients in their practice will be designated
      as "nonpediatric practitioners." METHODS: The authors aggregated multiple
      databases of professional neurosurgical societies in an effort to identify
      pediatric neurosurgical practitioners. A 30-question survey was then administered
      to all identified practitioners, and responses were collected for 6 months.
      Primary analysis of pediatric versus nonpediatric practitioners was performed.
      Subgroup analyses of the characteristics of the pediatric practitioners were also
      performed to identify the effects of practitioner age, sex, and practice setting
      on survey responses. RESULTS: A total of 342 practitioners received the survey,
      and 267 responded (78.1% response rate); 158 pediatric practitioners and 92
      nonpediatric practitioners were identified. Seventeen respondents were excluded
      from analysis. Pediatric practitioners were more likely to be women, ABPNS
      certified, have completed a pediatric fellowship, do fewer operative cases per
      year, have a more frequent call schedule, practice in a freestanding children's
      hospital, be in academic practice, and in need of recruiting additional faculty.
      Pediatric practitioners spent fewer hours per week in patient care, and were less
      likely to have a productivity-based salary or salary incentive based on relative
      value unit-production. Among pediatric practitioners, American Board of
      Neurological Surgery and ABPNS certification rates differed significantly among
      age groups, with older age groups being more likely to be certified by the
      American Board of Neurological Surgery and ABPNS. The rate of pediatric
      fellowship completion was significantly higher in the younger age groups.
      Anticipating retirement by age 65 was significantly more likely in the younger
      age groups, and hours spent per week spent in teaching and administrative duties
      were lower in the younger age groups. There were 27 female and 131 male pediatric
      practitioners. The women were more likely to have completed a pediatric
      fellowship and performed fewer operative cases per year than the men. Nonacademic
      pediatric practitioners were more likely to have a relative value unit-based
      salary incentive, be reimbursed for call coverage, and spend more hours per week
      in patient care than academic pediatric practitioners. Academic pediatric
      practitioners spent more hours per week in clinical research. CONCLUSIONS: The
      authors estimate that there are fewer than 200 pediatric neurosurgeons currently
      practicing in the United States. Current practice patterns unique to pediatrics
      may have important implications in recruiting and retaining the next generation
      of pediatric neurosurgeons.

PMID- 19119897
TI  - Intraventricular baclofen for dystonia: techniques and outcomes. Clinical
      article.
AB  - OBJECT: The aim of this study was to evaluate the use of intraventricular
      baclofen (IVB) for the treatment of severe generalized secondary and
      heredodegenerative dystonia. METHODS: Nine children and 1 adult with severe
      dystonia unresponsive to multiple oral medications were treated with IVB.
      Intraventricular catheters were positioned endoscopically in the third ventricle.
      RESULTS: Eight of the 10 patients responded to IVB; their mean dystonia scores on
      the Barry-Albright dystonia scale decreased from 23 to 8. The 2 patients who did
      not respond had not responded to previous high doses of intrathecal baclofen. No
      adverse side effects related to IVB occurred. One child developed a pump
      infection that required pump removal, 1 developed a CSF infection that cleared
      after antibiotic administration, and 1 developed ventriculomegaly that required a
      shunt placement. CONCLUSIONS: Intraventricular baclofen is an effective method of
      infusing baclofen to treat severe, generalized secondary dystonia, and, at times,
      heredodegenerative dystonia. The site of baclofen's activity when treating
      dystonia may be at the cortical level, and intraventricular infusion may result
      in higher baclofen concentrations over the cortex than intrathecal infusion.
      Additional studies are necessary to determine whether IVB is effective at lower
      doses than those used with intrathecal baclofen administration.

PMID- 19119899
TI  - Computed tomography morphometric analysis for C-1 lateral mass screw placement in
      children. Clinical article.
AB  - OBJECT: The use of C-1 lateral mass screws provides an alternative to C1-2
      transarticular screws in the pediatric population. However, the confined space of
      the local anatomy and unfamiliarity with the technique may make the placement of
      a C-1 lateral mass screw more challenging, especially in the juvenile or growing
      spine. METHODS: A CT morphometric analysis was performed in 76 pediatric atlases
      imaged at Texas Children's Hospital from October 1, 2007 until April 30, 2008.
      Critical measurements were determined for potential screw entry points,
      trajectories, and lengths, with the goal of replicating the operative technique
      described by Harms and Melcher for adult patients. RESULTS: The mean height and
      width for screw entry on the posterior surface of the lateral mass were 2.6 and
      8.5 mm, respectively. The mean medially angled screw trajectory from an idealized
      entry point on the lateral mass was 16 degrees (range 4 to 27 degrees ). The mean
      maximal screw depth from this same ideal entry point was 20.3 mm. The overhang of
      the posterior arch averaged 6.3 mm (range 2.1-12.4 mm). The measurement between
      the left- and right-side lateral masses was significantly different for the
      maximum medially angled screw trajectory (p = 0.003) and the maximum inferiorly
      directed angle (p = 0.045). Those measurements in children < 8 years of age were
      statistically significant for the entry point height (p = 0.038) and maximum
      laterally angled screw trajectory (p = 0.025) compared with older children. The
      differences between boys and girls were statistically significant for the minimum
      screw length (p = 0.04) and the anterior lateral mass height (p < 0.001).
      CONCLUSIONS: A significant variation in the morphological features of C-1 exists,
      especially between the left and right sides and in younger children. The
      differences between boys and girls are clinically insignificant. The critical
      measurement of whether the C-1 lateral mass in a child could accommodate a 3.5-mm
      diameter screw is the width of the lateral mass and its proximity to the
      vertebral artery. Only 1 of 152 lateral masses studied would not have been able
      to accommodate a lateral mass screw. This study reemphasizes the importance of a
      preoperative CT scan of the upper cervical spine to assure safe and effective
      placement of the instrumentation at this level.

PMID- 19119898
TI  - Jefferson fractures of the immature spine. Report of 3 cases.
AB  - Jefferson fractures of the immature spine have received little attention in the
      study of pediatric spinal trauma. Fractures through synchondroses are a
      possibility in the immature spine, in addition to fractures through osseous
      portions of the vertebral ring, and they create opportunities for
      misinterpretation of diagnostic imaging. The authors describe 3 examples of
      Jefferson fractures in young children. All 3 cases featured fractures through an
      anterior synchondrosis in association with persistence of the posterior
      synchondrosis or a fracture of the posterior arch. The possibility of a Jefferson
      fracture should be considered for any child presenting with neck pain, cervical
      muscle spasm, or torticollis following a head injury, despite a seemingly normal
      cervical spine study. Jefferson fractures in young children are probably much
      more common than previously recognized.

PMID- 19119900
TI  - Spinal congenital dermal sinus in a chick embryo model. Laboratory investigation.
AB  - OBJECT: The origin of spinal congenital dermal sinuses is not known. A local
      nondisjunction of the closing neural tube and the epidermal ectoderm is thought
      to be the cause of this malformation. In this experimental study, a
      nondisjunction was mimicked in chick embryos to create an animal model for the
      dermal sinus. METHODS: A piece of amniotic tissue was implanted in the closing
      neural tube in ovo in chick embryos at 2 days of incubation. A total of 50
      embryos were manipulated. After a further incubation time of 2-7 days, the
      embryos were macroscopically and histologically evaluated. RESULTS: Dermal sinus
      like anomalies were induced in 24 embryos. The induced abnormalities varied from
      superficial, epidermal lesions to epidermal dimples continuing as a strand of
      tissue toward the neural tube. This strand invariably was of nonneuronal origin.
      Additionally, in 3 embryos a split cord malformation was noted, most likely
      caused by damage to the neural tube during implantation. CONCLUSIONS:
      Implantation of donor amniotic tissue in the closing chick neural tube does
      result in a dimple, from which a strand of tissue continues to the neural tube in
      various cases, indicating that formation of a dermal sinus-like anomaly can be
      successfully induced by experimental continuation of the connection between
      neural tube and surface ectoderm. This finding strengthens the hypothesis that a
      human dermal sinus arises after nondisjunction of neural tube and surface
      ectoderm.

PMID- 19119902
TI  - Tentorial cavernous angioma with profuse bleeding. Case report.
AB  - This 15-year-old boy with a tentorial cavernous angioma reported occasional
      headache and scintillation in his left visual field. Magnetic resonance imaging
      revealed a well-demarcated, homogeneously enhanced tumor originating from the
      right cerebellar tentorium and extending into both the supratentorial and
      infratentorial spaces. Although a meningioma was suspected, vertebral artery
      angiography revealed a thickened meningeal branch originating from the right
      posterior inferior cerebellar artery and flecked tumor stain with pooling of
      contrast medium until the late venous phase. A cavernous angioma of the tentorium
      was suspected based on this finding, and as expected from the radiological
      findings, profuse bleeding was encountered during tumor removal. The histological
      diagnosis was a cavernous angioma. A cavernous angioma of the tentorium is
      extremely rare but should be differentiated from a meningioma preoperatively
      given that a cavernous angioma of dural origin tends to bleed massively during
      removal.

PMID- 19119901
TI  - Changes in cerebral perfusion hormone profile and cerebrospinal fluid flow across
      the third ventriculostomy after endoscopic third ventriculostomy in patients with
      aqueductal stenosis: a prospective study. Clinical article.
AB  - OBJECT: The object of the present study was 3-fold: 1) to study regional cerebral
      perfusion before and after endoscopic third ventriculostomy (ETV) in patients
      with obstructive hydrocephalus by using (99m)Tc ethyl cysteinate dimer SPECT: 2)
      to study any correlation between clinically successful third ventriculostomy and
      CSF flow across the third ventriculostomy; and 3) to determine any changes in
      hormone profile following ETV. METHODS: The authors prospectively studied 15
      patients with aqueductal stenosis who underwent ETV during the last 2 years. All
      the patients underwent pre- and postoperative MR imaging, brain (99m)Tc ethyl
      cysteinate dimer SPECT, and hormone profile studies. RESULTS: Eight patients were
      infants. The mean follow-up duration was 17.6 months. Thirteen patients (86.7%)
      exhibited clinical improvement after surgery. In all patients with clinical
      improvement the studies documented CSF flow through the ventriculostomy site.
      Clinical progress could be correlated with SPECT changes in 14 cases (93.3%). In
      the 13 clinically successful cases, 12 were substantiated by improvement on SPECT
      scans, whereas in the 2 failed cases, SPECT images revealed no improvement of
      perfusion defects. Hormone analysis conducted in 14 patients revealed
      hyperprolactinemia in 8, low triiodothyronine values in 2 patients, and
      hypocortisolemia in 1, which was reversed after ETV. CONCLUSIONS: Clinical
      improvement is not well correlated with a decrease in ventricular size following
      ETV. Brain SPECT is a valuable tool for the follow-up of patients with
      hydrocephalus after ETV, particularly in cases in which MR imaging findings are
      not clear. There are subtle hormonal changes in patients with hydrocephalus that
      may improve following ETV.

PMID- 19119903
TI  - Congenital cavernous hemangioma of the calvaria. Case report.
AB  - The authors present the case of a 6-month-old infant with a cavernous hemangioma
      of the parietal bone and discuss the radiological, operative, and pathological
      features and differential diagnosis of these extremely rare lesions in infants.
      Only 1 case of an infant with a calvarial cavernous hemangioma without
      intracranial invasion has previously been reported, and that case involved a 4
      month old. Although a cavernous hemangioma of the calvaria is extremely rare in
      the newborn, this condition should be included in the differential diagnosis of
      calvarial lesions. During surgical treatment of calvarial cavernous hemangiomas,
      utmost attention should be paid to avoid blood loss, which could be fatal in
      infants.

PMID- 19119904
TI  - Aggressive variant of a papillary glioneuronal tumor. Report of 2 cases.
AB  - Papillary glioneuronal tumors are a newly recognized type of brain neoplasm
      characterized by prominent pseudopapillary structures and glioneuronal elements.
      All prior cases have shown that these tumors have an indolent course. The authors
      present 2 patients with an aggressive variant of the tumor. The first patient had
      dissemination of her tumor and the second had local spreading. Therefore, the
      authors conclude that papillary glioneuronal tumors do not always behave in a
      strictly benign fashion.

PMID- 19119905
TI  - Arteriovenous shunting as a new feature of PHACES. Case report.
AB  - Patients with the congenital neurocutaneous disorder PHACES are at a markedly
      increased risk of ischemic infarction during childhood. Although intracranial
      arterial anomalies have been well described, venous abnormalities have not been
      documented. The authors report on a unique case of a 3-month-old girl with PHACES
      and a skull base osteodural arteriovenous fistula. A separate arteriovenous shunt
      at T-5 may also have been present. Imaging findings and treatment strategies are
      discussed.

PMID- 19119906
TI  - Pediatric spinal clear cell meningioma. Case report.
AB  - In this report the authors describe a unique case of spinal clear cell meningioma
      in a 13-year-old girl. Clear cell meningiomas (CCMs) are not uncommon. To the
      authors' knowledge, 14 cases of pediatric CCM occurring in the spinal canal have
      been reported. Factors lending resistance to meningioma initiation and invasion
      are analyzed. This 13-year-old girl presented with pain radiating down her left
      leg. Admission MR imaging showed an inhomogeneous enhancing intradural
      extramedullary mass at the L4-5 level. Resection revealed a CCM, and radiotherapy
      was subsequently administered. Postoperatively there has been no recurrence in >
      2 years. In this paper the authors report a case of CCM and provide a
      comprehensive literature review on this disease. Current recommendations for its
      management are still debatable, especially in the pediatric population, and the
      authors propose an algorithm for its treatment and surveillance.

PMID- 19119907
TI  - Low-level copy gain versus amplification of myc oncogenes in medulloblastoma:
      utility in predicting prognosis and survival. Laboratory investigation.
AB  - OBJECT: Medulloblastoma (MB) is a malignant embryonal tumor of the cerebellum.
      Amplification of c-myc or N-myc is infrequently identified and, when present, is
      often associated with the large cell/anaplastic (LC/A) phenotype. The frequency
      of low-level copy gain of myc oncogenes and its relationship to prognosis of MB
      has not been explored. METHODS: Archival cases of MB were histologically reviewed
      and classified into 3 major subtypes: classic, nodular, and LC/A. Using
      quantitative real-time polymerase chain reaction (PCR), the authors analyzed 58
      cases with a pure histological subtype for the copy number (CN) of myc (c-myc and
      N-myc) oncogenes. Cases with > 5-fold CN were further analyzed using the
      fluorescent in situ hybridization (FISH) assay. Kaplan-Meier survival analysis
      was performed. RESULTS: A > 5-fold myc CN was noted in 5 (20.8%) of 24 LC/A, 1
      (5.3%) of 19 classic, and 2 (13.3%) of 15 nodular subtypes. In a significant
      number of tumors (14 [56%] of 24 LC/A, 13 [68%] of 19 classic, and 10 [67%] of 15
      nodular MBs) the CN was > 2-fold but < 5-fold. High-level amplification, defined
      as > 10-fold CN, was only seen in the LC/A subtype (5 cases), although moderate
      amplification (> 5-fold but < 10-fold) could be detected in other histological
      subtypes. Fluorescence in situ hybridization readily detected most cases
      corresponding to tumors with > 5-fold amplicon CN by quantitative real-time PCR,
      and could detect all 5 cases with > 10-fold CN by quantitative real-time PCR. The
      group of patients with > 5-fold myc amplicon CN showed significantly shorter
      survival than those with < 5-fold CN (p = 0.045), independent of histological
      subtype. CONCLUSIONS: Since FISH could easily detect most cases in the moderate
      to-high myc gene amplification (> 5-fold CN) group, the FISH assay has utility in
      detecting subsets of MB with poorer prognosis.

PMID- 19119908
TI  - Decompressive craniectomy in children with nontraumatic refractory high
      intracranial pressure. Clinical article.
AB  - OBJECT: In this study, the authors investigated the clinical efficacy of
      decompressive craniectomy treatments for nontraumatic intracranial hypertension
      in children. METHODS: Seven patients with nontraumatic refractory high
      intracranial pressure (ICP) were enrolled in the study between 1995 and 2005;
      there were 2 boys and 5 girls with a mean age of 9 years (range 4-14).
      Decompressive craniectomy was performed in all patients after standard medical
      therapy had proven insufficient and ICP remained > 50 mm Hg. All patients had a
      Glasgow Coma Scale score < 8 at admission and a mean Pediatric Risk of Mortality
      Scale score of 20 (range 10-27). RESULTS: One patient died of persistent high ICP
      and circulatory failure 48 hours after surgery. Six months later, according to
      their Glasgow Outcome Scale scores, 3 patients had adequate recoveries, 2
      patients recovered with moderate disabilities, and 1 patient had severe
      disabilities. According to the Pediatric Overall Performance Category Scale, 4
      patients received a score of 2 (mild disability), 1 a score of 3 (moderate
      disability), and 1 a score of 4 (severe disability). Five patients returned to
      school and normal life. CONCLUSIONS: The authors found decompressive craniectomy
      to be an effective and lifesaving technique in children. This procedure should be
      included in the arsenal of treatments for nontraumatic intracranial hypertension.

PMID- 19119909
TI  - Active spontaneous decompression of a suprasellar-prepontine arachnoid cyst
      detected with routine magnetic resonance imaging. Case report.
AB  - Arachnoid cysts are congenital CSF collections that arise adjacent to arachnoid
      cisterns. These lesions can be incidental neuroimaging findings but may also
      cause symptoms and necessitate treatment, particularly in children. The authors
      present their experience with a male infant harboring a large suprasellar
      prepontine arachnoid cyst who underwent spontaneous decompression into the
      ventricular system, as evidenced by a visualized CSF flow jet observed on routine
      MR imaging.

PMID- 19119910
TI  - Management of vagal nerve stimulator infections: do they need to be removed?
AB  - OBJECT: Vagal nerve stimulators (VNSs) have been used successfully to treat
      medically refractory epilepsy. Although their efficacy is well established,
      appropriate management of infections is less clearly defined. In the authors'
      experience, patients who have gained a benefit from VNS implantation have been
      reluctant to have the device removed. The authors therefore sought conservative
      management options to salvage infected VNS systems. METHODS: The authors
      performed a retrospective review of 191 (93 female and 98 male) consecutive
      patients in whom VNS systems were placed between 2000 and 2007. RESULTS: They
      identified 10 infections (5.2%). In 9 of 10 patients the cultured organism was
      Staphylococcus aureus. Three (30%) of 10 patients underwent early removal (within
      1 month) of the VNS as the initial treatment. The remaining 7 patients were
      initially treated with antibiotics. Two (28.6%) of these patients were
      successfully treated using antibiotics without VNS removal. Patients in whom
      conservative treatment failed were given cephalexin as first-line antibiotic
      treatment. All patients recovered completely regardless of treatment regimen.
      CONCLUSIONS: This study confirms the low rate of infection associated with VNS
      placement and suggests that, in the case of infection, treatment without removal
      is a viable option. However, the authors' data suggest that oral antibiotics are
      not the best first-line therapy.

PMID- 19119911
TI  - Ossified pseudomeningocele.

PMID- 19119912
TI  - Imaging of the 3D nanostructure of a polymer solar cell by electron tomography.
AB  - Electron tomography has been used for analyzing the active layer in a polymer
      solar cell, a bulk heterojunction of an alternating copolymer of fluorene and a
      derivative of fullerene. The method supplies a three-dimensional representation
      of the morphology of the film, where domains with different scattering properties
      may be distinguished. The reconstruction shows good contrast between the two
      phases included in the film and demonstrates that electron tomography is an
      adequate tool for investigations of the three-dimensional nanostructure of the
      amorphous materials used in polymer solar cells.

PMID- 19119913
TI  - Proteomic profiling of the insoluble pellets of the transected rat spinal cord.
AB  - This study investigated the proteomic changes at different time points in the
      precipitated pellets of rat spinal cords after applying complete spinal cord
      transection. By two-dimensional electrophoresis, matrix-assisted laser
      desorption/ionization time of flight (MALDI-TOF) mass spectrometry, MALDI-TOF/TOF
      and peptide mass fingerprinting analysis, 44 proteins were identified, most of
      which are membrane and/or organellar proteins. They are mainly involved in
      metabolic processes (75%), developmental processes (30%), or responses to stimuli
      (30%), playing negative or positive roles. In particular, decreases of pyruvate
      dehydrogenase beta, aconitase 2, fumarate hydratase 1, and ATP synthase subunit 6
      can lead to ATP depletion by crippling tricarboxylic acid cycle and oxidative
      phosphorylation. Decreases of several antioxidant proteins such as catalase,
      peroxiredoxin 1, Parkinson disease 7, and stress-induced phosphoprotein 1 can
      contribute to the secondary injury of spinal cord. Decreases of development
      related 3-phosphoglycerate dehydrogenase and stathmin 1 may be not propitious for
      spinal cord regeneration. On the other hand, increases of isocitrate
      dehydrogenase 3 alpha/gamma and glutamate dehydrogenase 1 can help compensate the
      impaired energy metabolism. Increases of sirtuin 2, crystallin alpha B (CRYAB),
      and heat shock 27-kDa protein 1 can help resist stresses induced by injury.
      Increases of adenylate cyclase-associated protein 1 and galactose binding lectin
      3 can help regeneration by replaying their roles in neural development. To our
      knowledge, this is the first case of characterization of the proteomic changes
      seen in the precipitated fraction of injured spinal cord. Most of the identified
      proteins were found for the first time to be differentially expressed after
      spinal cord injury, which may provide new clues about the molecular mechanisms of
      spinal cord injury and repair.

PMID- 19119914
TI  - COG1410 improves cognitive performance and reduces cortical neuronal loss in the
      traumatically injured brain.
AB  - We have previously shown that a single dose of COG1410, a small molecule ApoE
      mimetic peptide derived from the apolipoprotein E (ApoE) receptor binding region,
      improves sensorimotor and motor outcome following cortical contusion injury
      (CCI). The present study evaluated a regimen of COG1410 following frontal CCI in
      order to examine its preclinical efficacy on cognitive recovery. Animals were
      prepared with a bilateral CCI of the frontal cortex. A regimen of COG1410
      (0.8mg/kg intravenously [IV]) was administered twice, at 30min and again at 24h
      post-CCI. Starting on day 11, the animals were tested for their acquisition of a
      reference memory task in the Morris water maze (MWM), followed by a working
      memory task in the MWM on day 15. Following CCI, the animals were also tested on
      the bilateral tactile adhesive removal test to measure sensorimotor dysfunction.
      On all of the behavioral tests the COG1410 group was no different from the
      uninjured sham group. Administration of the regimen of COG1410 significantly
      improved recovery on the reference and working memory tests, as well as on the
      sensorimotor test. Lesion analysis revealed that COG1410 significantly reduced
      the size of the injury cavity. Administration of COG1410 also reduced the number
      of degenerating neurons, as measured by Fluoro-Jade C staining, in the frontal
      cortex at 48h post-CCI. These results suggest that a regimen of COG1410 appeared
      to block the development of significant behavioral deficits and reduced tissue
      loss. These combined findings suggest that COG1410 appears to have strong
      preclinical efficacy when administered following traumatic brain injury (TBI).

PMID- 19119915
TI  - Spinal hyperexcitability and bladder hyperreflexia during reversible frontal
      cortical inactivation induced by low-frequency electrical stimulation in the cat.
AB  - Spinal hyperexcitability and hyperreflexia gradually develop in the majority of
      stroke patients. These pathologies develop as a result of reduced cortical
      modulation of spinal reflexes, mediated largely indirectly via relays in the
      brainstem and other subcortical structures. Cortical control of spinal reflexes
      is markedly different in small animals, such as rodents, while in some larger
      species, such as cats, it is more comparable to that in humans. In this study, we
      developed a novel model of stroke in the cat, with controllable and reversible
      inhibition of cortical neuronal activity appearing approximately 1h after
      initiation of low-frequency electrical stimulation in the frontal cerebral
      cortex, evidenced by a large increase in the alpha frequency band (7-14 Hz) of
      the frontal electrocorticographic signal. Hyperreflexia of the urinary bladder
      developed 3h or more after induction of reversible cortical inactivation with
      optimized stimulation parameters (frequency of 1-2 Hz, amplitude of 10 mA,
      applied for 30 min). The bladder hyperreflexia persisted for at least 8h, and
      disappeared within 24h. At the S2 level of the spinal cord, where neural circuits
      mediating micturition and other pelvic reflexes reside, we have recorded an
      increase in neuronal activity correlated with the development of hyperreflexia.
      The low-frequency stimulation-induced reversible cortical inactivation model of
      stroke is highly reproducible and allows evaluation of spinal hyperexcitability
      and hyperreflexia using within-animal comparisons across experimental conditions,
      which can be of great value in examination of mechanisms of spinal hyperreflexia
      following stroke or brain trauma, and for developing more effective treatments
      for these conditions.

PMID- 19119917
TI  - NNZ-2566, a glypromate analog, improves functional recovery and attenuates
      apoptosis and inflammation in a rat model of penetrating ballistic-type brain
      injury.
AB  - Glycine-proline-glutamate (GPE) is an N-terminal tripeptide endogenously cleaved
      from insulin-like growth factor-1 in the brain and is neuroprotective against
      hypoxic-ischemic brain injury and neurodegeneration. NNZ-2566 is an analog of GPE
      designed to have improved bioavailability. In this study, we tested NNZ-2566 in a
      rat model of penetrating ballistic-type brain injury (PBBI) and assessed its
      effects on injury-induced histopathology, behavioral deficits, and molecular and
      cellular events associated with inflammation and apoptosis. In the initial dose
      response experiments, NNZ-2566 (0.01-3 mg/kg/h x 12 h intravenous infusion) was
      given at 30 min post-injury and the therapeutic time window was established by
      delaying treatments 2-4 h post-injury, but with the addition of a 10- or 30-mg/kg
      bolus dose. All animals survived 72 h. Neuroprotection was evaluated by balance
      beam testing and histopathology. The effects of NNZ-2566 on injury-induced
      changes in Bax and Bcl-2 proteins, activated microgliosis, neutrophil
      infiltration, and astrocyte reactivity were also examined. Behavioral results
      demonstrated that NNZ-2566 dose-dependently reduced foot faults by 19-66% after
      acute treatments, and 35-55% after delayed treatments. Although gross lesion
      volume was not affected, NNZ-2566 treatment significantly attenuated neutrophil
      infiltration and reduced the number of activated microglial cells in the peri
      lesion regions of the PBBI. PBBI induced a significant upregulation in Bax
      expression (36%) and a concomitant downregulation in Bcl-2 expression (33%), both
      of which were significantly reversed by NNZ-2566. Collectively, these results
      demonstrated that NNZ-2566 treatment promoted functional recovery following PBBI,
      an effect related to the modulation of injury-induced neural inflammatory and
      apoptotic mechanisms.

PMID- 19119916
TI  - Mechanistic and kinetic details of catalysis of thiol-disulfide exchange by
      glutaredoxins and potential mechanisms of regulation.
AB  - Glutaredoxins are small, heat-stable proteins that exhibit a characteristic
      thioredoxin fold and a CXXC/S active-site motif. A variety of glutathione (GSH)
      dependent catalytic activities have been attributed to the glutaredoxins,
      including reduction of ribonucleotide reductase, arsenate, and dehydroascorbate;
      assembly of iron sulfur cluster complexes; and protein glutathionylation and
      deglutathionylation. Catalysis of reversible protein glutathionylation by
      glutaredoxins has been implicated in regulation of redox signal transduction and
      sulfhydryl homeostasis in numerous contexts in health and disease. This forum
      review is presented in two parts. Part I is focused primarily on the mechanism of
      the deglutathionylation reaction catalyzed by prototypical dithiol glutaredoxins,
      especially human Grx1 and Grx2. Grx-catalyzed protein deglutathionylation
      proceeds by a nucleophilic, double-displacement mechanism in which rate
      enhancement is attributed to special reactivity of the low pK(a) cysteine at its
      active site, and to increased nucleophilicity of the second substrate, GSH.
      Glutaredoxins (and Grx domains) have been identified in most organisms, and many
      exhibit deglutathionylation or other activities or both. Further characterization
      according to glutathionyl selectivity, physiological substrates, and
      intracellular roles may lead to subclassification of this family of enzymes. Part
      II presents potential mechanisms for in vivo regulation of Grx activity,
      providing avenues for future studies.

PMID- 19119918
TI  - Genetic ablation of transcription repressor Bach1 reduces neural tissue damage
      and improves locomotor function after spinal cord injury in mice.
AB  - Heme oxygenase (HO)-1 is an inducible cytoprotective enzyme that degrades heme to
      iron, carbon monoxide (CO), and biliverdin, the latter two of which are thought
      to mediate the anti-inflammatory and antioxidant actions of HO-1. Bach1 is a
      transcriptional repressor of the HO-1 gene (Hmox-1). Previous reports have
      demonstrated that the genetic ablation of Bach1 engenders an increased HO-1
      expression and a marked reduction in the degree of oxidative tissue damage in
      vivo. However, the function of Bach1 in spinal cord injury is still not
      understood. In the present study, we examined whether Bach1 deficiency increases
      HO-1 expression and reduces neural tissue damage in a spinal cord injury model
      using Bach1 knock-out (KO) mice and wild-type (WT) mice. The expression of HO-1
      protein in the spinal cord was significantly higher in the Bach1 KO mice than in
      the WT mice before and after injury. The KO mice also had significantly higher
      Basso mouse scale scores for locomotor function and larger areas of spared white
      matter than the WT mice at 6 weeks after injury. Neuronal loss and apoptotic cell
      death in the injured spinal cord was significantly reduced in the KO mice in
      comparison to the WT mice. These results suggest that Bach1 deficiency engenders
      a constitutively higher expression of HO-1 and a dramatic increase in
      cytoprotection against spinal cord injury.

PMID- 19119919
TI  - An endophytic fungus from Camptotheca acuminata that produces camptothecin and
      analogues.
AB  - The pentacyclic quinoline alkaloid camptothecin (1) is a potent antineoplastic
      agent. Two of its analogues, 9-methoxycamptothecin (2) and 10-hydroxycamptothecin
      (3), exhibit similar potency but do not have the potential therapeutic drawbacks
      produced by unmodified 1. We have established methodology for the isolation and
      unequivocal identification and characterization of a novel endophytic fungus
      isolated from the inner bark of the medicinal plant Camptotheca acuminata, which
      produced 1-3 in rich mycological medium (Sabouraud dextrose broth), under shake
      flask fermentation conditions. The fungus was identified by its morphology and
      authenticated by ITS analysis (ITS1 and ITS2 regions and the intervening 5.8S
      rDNA region). Camptothecin (1) and its analogues were identified by 1H NMR
      spectroscopy and LC-HRMS and confirmed by comparison with authentic standards.
      The production pattern of the metabolites over seven successive subculture
      generations of this endophyte was studied. A sharp attenuation in the production
      of 1 and 2 was observed from the first- through to the seventh-generation
      subculture. Therefore, these results offer a caution as to the possibility of
      using endophytic fungi as alternate sources of plant secondary metabolite
      production. Further studies have been initiated on the analysis of the upstream
      metabolic intermediates to understand the steps at which the production of the
      metabolites in question is constrained.

PMID- 19119921
TI  - In vitro evaluation of macroporous hydrogels to facilitate stem cell
      infiltration, growth, and mineralization.
AB  - Hydrogels have gained acceptance as biomaterials in a wide range of applications,
      including pharmaceutical formulations, drug delivery, and tissue sealants.
      However, exploiting the potential of hydrogels as scaffolds for cell
      transplantation, tissue engineering, and regenerative medicine still remains a
      challenge due to, in part, scaffold design limitations. Here, we describe a
      highly interconnected, macroporous poly(ethylene glycol) diacrylate hydrogel
      scaffold, with pores ranging from 100 to 600 microm. The scaffold exhibits rapid
      cell uptake and cell seeding without the need of any external force or device
      with high incorporation efficiency. When human mesenchymal stem cells are seeded
      within the porous scaffolds, the scaffolds were found to promote long-term stem
      cell viability, and on exposure to osteogenic medium, elicit an mineralization
      response as evaluated by an increased alkaline phosphatase activity (per cell)
      and calcium and phosphate content within the constructs. The atomic composition
      of the mineralized matrix was further determined by energy dispersive
      spectroscopy and found to be similar to calcium-deficient hydroxyapatite, the
      amorphous biological precursor of bone. The macroporous design of the hydrogel
      appears advantageous over similar porous hydrogel scaffolds with respect to ease
      of synthesis, ease of stem cell seeding, and its ability to support long-term
      stem cell survival and possible differentiation.

PMID- 19119920
TI  - Differential maturation and structure-function relationships in mesenchymal stem
      cell- and chondrocyte-seeded hydrogels.
AB  - Degenerative disease and damage to articular cartilage represents a growing
      concern in the aging population. New strategies for engineering cartilage have
      employed mesenchymal stem cells (MSCs) as a cell source. However, recent work has
      suggested that chondrocytes (CHs) produce extracellular matrix (ECM) with
      superior mechanical properties than MSCs do. Because MSC-biomaterial interactions
      are important for both initial cell viability and subsequent chondrogenesis, we
      compared the growth of MSC- and CH-based constructs in three distinct hydrogels
      agarose (AG), photocrosslinkable hyaluronic acid (HA), and self-assembling
      peptide (Puramatrix, Pu). Bovine CHs and MSCs were isolated from the same group
      of donors and seeded in AG, Pu, and HA at 20 million cells/mL. Constructs were
      cultured for 8 weeks with biweekly analysis of construct physical properties,
      viability, ECM content, and mechanical properties. Correlation analysis was
      performed to determine quantitative relationships between formed matrix and
      mechanical properties for each cell type in each hydrogel. Results demonstrate
      that functional chondrogenesis, as evidenced by increasing mechanical properties,
      occurred in each MSC-seeded hydrogel. Interestingly, while CH-seeded constructs
      were strongly dependent on the 3D environment in which they were encapsulated,
      similar growth profiles were observed in each MSC-laden hydrogel. In every case,
      MSC-laden constructs possessed mechanical properties significantly lower than
      those of CH-seeded AG constructs. This finding suggests that methods for inducing
      MSC chondrogenesis have yet to be optimized to produce cells whose functional
      matrix-forming potential matches that of native CHs.

PMID- 19119922
TI  - Enhanced tissue integration during cartilage repair in vitro can be achieved by
      inhibiting chondrocyte death at the wound edge.
AB  - OBJECTIVE: Experimental wounding of articular cartilage results in cell death at
      the lesion edge. The objective of this study was to investigate whether
      inhibition of this cell death results in enhanced integrative cartilage repair.
      METHODS: Bovine articular cartilage discs (6 mm) were incubated in media
      containing inhibitors of necrosis (Necrostatin-1, Nec-1) or apoptosis (Z-VAD-FMK,
      ZVF) before cutting a 3 mm inner core. This core was left in situ to create
      disc/ring composites, cultured for up to 6 weeks with the inhibitors, and
      analyzed for cell death, sulfated glycosaminoglycan release, and tissue
      integration. RESULTS: Creating the disc/ring composites resulted in a significant
      increase in necrosis. ZVF significantly reduced necrosis and apoptosis at the
      wound edge. Nec-1 reduced necrosis. Both inhibitors reduced the level of wound
      induced sulfated glycosaminoglycan loss. Toluidine blue staining and electron
      microscopy of cartilage revealed significant integration of the wound edges in
      disc/ring composites treated with ZVF. Nec-1 improved integration, but to a
      lesser extent. Push-out testing revealed that ZVF increased adhesive strength
      compared to control composites. CONCLUSIONS: This study shows that treatment of
      articular cartilage with cell death inhibitors during wound repair increases the
      number of viable cells at the wound edge, prevents matrix loss, and results in a
      significant improvement in cartilage-cartilage integration.

PMID- 19119923
TI  - Ultrasonic and electromagnetic enhancement of a culture of human SAOS-2
      osteoblasts seeded onto a titanium plasma-spray surface.
AB  - Several studies suggest that the surface coating of titanium could play an
      important role in bone tissue engineering. In the present study, we have followed
      a particular biomimetic strategy where ultrasonically or electromagnetically
      stimulated SAOS-2 human osteoblasts proliferated and built their extracellular
      matrix on a titanium plasma-spray surface. In comparison with control conditions,
      the ultrasonic stimulation (average power, 149 mW; frequency, 1.5 MHz) and the
      electromagnetic stimulation (magnetic field intensity, 2 mT; frequency, 75 Hz)
      caused higher cell proliferation, and increased surface coating with decorin,
      osteocalcin, osteopontin, and type I collagen together with higher incorporation
      of calcium and phosphorus inside the extracellular matrix. The immunofluorescence
      related to the preceding bone matrix proteins showed their colocalization in the
      cell-rich areas. The use of the two physical stimulations aimed at obtaining the
      coating of the rough titanium plasma-spray surface in terms of cell colonization
      and deposition of extracellular matrix. The superficially cultured biomaterial
      could be theoretically used, in clinical applications, as an implant for bone
      repair.

PMID- 19119924
TI  - The timing of surgery in patients with central spinal cord injury.

PMID- 19119925
TI  - Effectiveness of surgical treatment for traumatic central cord syndrome.
AB  - OBJECT: The authors undertook a study in patients with traumatic central cord
      syndrome (TCCS) who underwent surgical intervention. They retrospectively
      assessed the motor score improvement and functional status and identified
      prognostic predictors of improvement. METHODS: Between March 1999 and May 2004,
      49 patients with TCCS were surgically treated. Motor scores were collected at
      admission and follow-up using the American Spinal Injury Association (ASIA)
      Impairment Scale. The 36-Item Short Form Health Survey (SF-36) was administered.
      Other parameters including walking index, spasticity, bladder management, and
      neuropathic pain scores were recorded. Patients were asked to assess their level
      of satisfaction with their final symptoms. RESULTS: The average ASIA score,
      converted into numeric values, was increased from 54.9 at admission to 81.9 and
      89.6 at 6 months and final follow-up, respectively. Significant improvement of
      ASIA score was achieved within the first 6 months of surgery. No significant
      difference was found between patients who underwent surgery within 4 days of
      injury or after 4 days of injury, adopting different approaches (anterior,
      posterior, or a combination), or with different pathological entities (acute disc
      herniation, fracture or dislocation, or multilevel degeneration). The ASIA score
      improvement had a positive correlation with the age at injury (r = 0.505, p =
      0.023). The SF-36 data at 6 months and final follow-up were not as satisfactory
      as the improvement in ASIA scores, and almost one-third of patients expressed
      dissatisfaction with their final symptoms. For patients who were older than 65
      years at injury, the mean follow-up Walking Index for Spinal Cord Injury (WISCI)
      score was statistically lower than it was in younger patients. The presence of
      spasticity or neuropathic pain at follow-up was not related to age, sex, ASIA
      motor score, or WISCI outcome. CONCLUSIONS: Surgical intervention can be safely
      applied in patients with TCCS. Significant improvement of ASIA score was achieved
      during the first 6-month period of follow-up. Factors including type of lesion,
      timing of surgery within or after 4 days of injury, and surgical approach were
      not significantly associated with final ASIA score. The improvement in the ASIA
      motor score was positively correlated with age at injury. No significant
      correlation was found between or among the presence of spasticity, neuropathic
      pain, and ASIA score at final visit. Almost one-third of patients were not
      satisfied with their final symptoms.

PMID- 19119926
TI  - Effect of hyperglycemia on progressive paraparesis in a rat etastatic spinal
      tumor model.
AB  - OBJECT: Hyperglycemia has been shown to potentiate ischemic injury of the spinal
      cord by quenching vasodilators and potentiating tissue acidosis and free radical
      production. Steroid-induced hyperglycemia is a common event in the surgical
      management of metastatic epidural spinal cord compression (MESCC). The goal in
      this study was to determine whether experimentally induced hyperglycemia
      accelerates neurological decline in an established animal model of MESCC.
      METHODS: Sixteen Fischer 344 rats underwent a transabdominal approach for
      implantation of a CRL-1666 breast adenocarcinoma cell line within the vertebral
      body of L-6. After 72 hours of recovery from tumor implantation, the animals
      received intraperitoneal injections every 12 hours of either 2 g/kg dextrose in 5
      ml 0.09% saline (hyperglycemia, 8 rats) or 5 ml 0.09% saline alone
      (normoglycemia, 8 rats). Weights were taken daily, and the hindlimb function was
      tested daily after tumor implantation by using the Basso-Beattie-Bresnahan (BBB)
      scale (score range 1-21). Animals were killed at time of paralysis (BBB Score <
      7), and the volume of epidural tumor growth within the spinal canal was measured.
      To determine the degree of hyperglycemia induced by this dextrose regimen, a
      surrogate group of 10 Fischer 344 rats underwent intraperitoneal injections of 2
      g/kg dextrose (5 rats) or 0.09% saline (5 rats) every 12 hours, and serum glucose
      levels were assessed 1, 3, 6, 8, 10, and 12 hours after injections for 24 hours.
      RESULTS: Dextrose versus saline injections resulted in elevated mean serum
      glucose at 3 (259 vs 103 microg/dl), 6 (219 vs 102 microg/dl), 8 (169 vs 102
      microg/dl), and 10 hours (118 vs 99 microg/dl) after injection, returning to
      normal levels by 12 hours (96 vs 103 microg/dl) just prior to subsequent
      injection. All rats had normal hindlimb function for the first 8 days after tumor
      implantation. Hyperglycemic versus normoglycemic rats demonstrated a worsened
      median BBB score by postimplantation Day 9 (Score 20 vs 21, p = 0.023) through
      Day 16 (Score 8 vs 12, p = 0.047). Epidural tumor volume demonstrated a near
      linear growth rate across both groups; however, hyperglycemic rats developed
      paralysis earlier (median 15.5 vs 17.5 days, p = 0.0035), with significantly less
      epidural tumor volume (2.75 +/- 0.38 cm(3) vs 4 +/- 0.41 cm(3), p < 0.001) at
      time of paralysis. CONCLUSIONS: In a rat model of metastatic epidural spinal cord
      compression, rats maintained in a hyperglycemic state experienced accelerated
      time to paralysis. Also, less epidural tumor volume was required to cause
      paralysis in hyperglycemic rats. These results suggest that hyperglycemic states
      may contribute to decreased spinal cord tolerance to compression resulting from
      MESCC. Clinical studies evaluating the effect of aggressive glucose control in
      patients with MESCC may be warranted.

PMID- 19119927
TI  - Role of hyperbaric oxygen therapy in the treatment of bacterial spinal
      osteomyelitis.
AB  - OBJECT: Hyperbaric oxygen therapy (HBO) is used as primary and/or adjunctive
      therapy in the treatment of various clinical conditions complicated by local
      hypoxia. It may have therapeutic potential in the treatment of neurosurgical
      infections such as spinal osteomyelitis that are associated with significant
      morbidity rates. The purpose of this study was to evaluate the efficacy of HBO
      therapy in the treatment of spinal osteomyelitis. METHODS: The clinical records
      of patients diagnosed with spinal osteomyelitis who received HBO therapy during
      their treatment at the authors' institution over the past 10 years were
      retrospectively reviewed. Six adult patients were identified. Four patients had
      recently undergone spinal surgery and secondary spinal osteomyelitis had
      developed. These patients received adjunctive HBO therapy due to significant
      comorbidities and risk factors for poor healing. RESULTS: All patients remained
      symptom and infection free over the subsequent follow-up period. Two patients had
      primary spinal osteomyelitis that had recurred despite a full course of
      appropriate antimicrobial therapy. Infection control was achieved after HBO
      therapy in 1 patient. The mean follow-up period for the study group was 2.9 years
      (range 5 months to 5 years). CONCLUSIONS: Hyperbaric oxygen therapy enabled
      infection cure in 5 of 6 patients with spinal osteomyelitis complicated by
      medical comorbidities or the failure of primary therapy. These results show that
      HBO may be a useful adjunctive therapeutic modality in the treatment of spinal
      osteomyelitis, particularly when there are medical comorbidities that increase
      the risk of poor healing. Hyperbaric oxygen therapy may also be beneficial in
      patients with relapsing primary spinal osteomyelitis after standard therapy has
      failed.

PMID- 19119928
TI  - Image-based drill templates for cervical pedicle screw placement.
AB  - OBJECT: Pedicle screws (PSs) in the cervical spine can provide fixation superior
      to current fixation methods; however, their implementation is challenging due to
      the small size of the cervical vertebrae. In this study, the authors explored and
      evaluated the use of patient-specific, rapid prototype drill templates for PS
      placement in the cervical spine. The goal of the study was to assess the accuracy
      of a drill template in the placement of cervical PSs at a single vertebral level.
      METHODS: Volumetric CT scanning was performed in 4 cadaveric cervical spines.
      Using computer software, the authors constructed drill templates with a
      predefined trajectory designed to match the posterior surface of vertebrae C3-7.
      Twenty physical templates were created from the computer models using a rapid
      prototyping machine. The drill templates were used to guide pilot-hole drilling,
      and CT scanning was performed to assess the accuracy of the pilot holes. Pedicle
      screws (3.5-mm diameter) were placed in the pilot holes. The spines were then
      dissected to separate the vertebrae, and the trajectory of the screws was
      visually inspected. RESULTS: The feasibility of this patient-specific, rapid
      prototyping technique was demonstrated. Imaging and visual inspection of pilot
      holes and cervical PSs revealed that the majority of trajectories did not violate
      the pedicle cortex (19 [95%] of 20). The single cortical violation was judged as
      noncritical and would probably not have resulted in injury to a patient.
      CONCLUSIONS: The potential of drill templates to aid in the placement of cervical
      PSs is promising. The authors' methods appear to provide an accurate technique
      and trajectory for PS placement in the cervical spine.

PMID- 19119929
TI  - Rapid magnetic resonance imaging-guided reduction of craniovertebral junction
      deformities.
AB  - The authors demonstrate the utility of an MR imaging-compatible traction board
      for the rapid reduction of craniovertebral junction (CVJ) deformities. To choose
      the appropriate surgical management, patients with compressive CVJ deformities
      often undergo a trial of traction. Conventional traction trials require the
      treating surgeon to infer from plain radiographs the manner in which traction
      forces affect neural and ligamentous structures at the CVJ. To avoid
      overdistraction injury, low increments of weight are added in a gradual fashion,
      a process that typically requires 48-72 hours. The authors outline the use of an
      MR imaging-compatible traction board to determine reducibility safely and rapidly
      in 4 patients with compressive CVJ deformities. Four patients with advanced CVJ
      deformities underwent a trial of MR imaging-guided traction performed using an MR
      imaging-compatible spine board. Serial sagittal images were acquired at baseline
      and following each sequential addition of force. All patients tolerated traction
      without neurological worsening. The neural elements were seen to be adequately
      decompressed in all cases during a single MR imaging session. Patients
      subsequently underwent craniocervical stabilization and fusion. Postoperative
      imaging showed maintenance of the reduction without neural compression. An MR
      imaging-guided trial of traction can facilitate the rapid and safe determination
      of the reducibility of compressive lesions in patients with advanced CVJ
      deformities. Rapidly acquired sagittal MR images permit the surgeon to evaluate
      the effects of traction on the soft tissues at the CVJ, thereby expediting the
      traction trial and avoiding the risks of immobility in this often-fragile patient
      population.

PMID- 19119930
TI  - Placement of thoracolumbar pedicle screws using three-dimensional image guidance:
      experience in a large patient cohort.
AB  - OBJECT: The goal of this study was to analyze the placement accuracy and
      complications of thoracolumbar pedicle screws (PSs) inserted using 3D image
      guidance in a large patient cohort. METHODS: The authors reviewed the charts of
      220 consecutive patients undergoing posterior spinal fusion using 3D image
      guidance for instrumentation placement. A total of 1084 thoracolumbar PSs were
      placed using either the BrainLAB Vector Vision (BrainLAB, Inc.) or Medtronic
      StealthStation Treon (Medtronic, Inc.) image guidance systems. Postoperative CT
      scanning was performed in 184 patients, allowing for 951 screws to be graded by
      an independent radiologist for bone breach. All complications resulting from
      instrumentation placement were noted. Using the intraoperative planning function
      of the image-guided system, the largest diameter screw possible in each
      particular case was placed. The screw diameter of instrumentation placed into the
      L3-S1 levels was noted. RESULTS: No vascular or visceral complications occurred
      as a result of screw placement. Two nerve root injuries occurred in 1084 screws
      placed, resulting in a 0.2% per screw incidence and a 0.9% patient incidence of
      nerve root injury. Neither nerve root injury was associated with a motor deficit.
      The breach rate was 7.5%. Grade 1 and minor anterolateral "tip out" breaches
      accounted for 90% of the total breaches. Patients undergoing revision surgery
      accounted for 46% of the patients in this study. Accordingly, 154 screws placed
      through previous fusion mass could be evaluated using postoperative CT scanning.
      The breach rate in this specific cohort was 7.8%. A total of 765 PSs were placed
      into the L3-S1 levels in this study; 546 (71%) of these screws were > or = 7.5 mm
      in diameter. No statistical difference in breach rate was noted in PSs placed
      through revision spinal levels versus nonrevision spinal levels (p = 0.499).
      Additionally, no increase in breach rate was noted with placement of 7.5-mm
      diameter screws. CONCLUSIONS: Three-dimensional image guidance is a useful
      adjunct to placement of spinal instrumentation. The complication rate in this
      study was low, and accurate placement of instrumentation was achieved despite the
      high percentage of revision surgery cases in our patient population.
      Additionally, because active fluoroscopy was not used for instrumentation
      placement, there was minimal to no radiation exposure to the surgeon or operating
      room staff.

PMID- 19119931
TI  - Trap-door rib-head osteotomies for posterior placement of expandable cages after
      transpedicular corpectomy: an alternative to lateral extracavitary and
      costotransversectomy approaches.
AB  - Lateral extracavitary and costotransversectomy approaches have been well
      described, and they are useful for posterior thoracic corpectomies. However,
      these approaches require pleural dissection and are associated with
      welldocumented morbidities, including hemothorax, pneumothorax, and pneumonia.
      But without removing the rib head, the window through which an expandable cage
      can be placed from a posterior approach is narrow. Thus, smaller nonexpandable
      mesh cages or methylmethacrylate constructs are commonly used for anterior column
      reconstruction. The authors describe a technique of using a "trap-door" rib-head
      osteotomy that avoids pleural dissection, yet allows a large expandable cage to
      be placed from an entirely posterior approach.

PMID- 19119932
TI  - Mini-open removal of extradural foraminal tumors of the lumbar spine.
AB  - Spinal extradural foraminal neoplasms are uncommon lesions that are traditionally
      resected via an open laminectomy and facetectomy approach. In this paper the
      authors present their mini-open approach for the removal of 3 such tumors. The
      authors retrospectively reviewed 3 patients with extradural schwannoma who
      underwent mini-open resection and fusion between June 2006 and July 2007.
      Clinical data, tumor characteristics, and outcomes were analyzed. All 3 patients
      underwent successful mini-open treatment of their spinal neoplasms. Postoperative
      MR imaging demonstrated complete resection in 2 cases and subtotal resection in 1
      case. Extradural foraminal neoplasms can be safely and effectively treated with
      mini-open techniques. Reductions in blood loss, hospitalization, and tissue
      disruption may be potential benefits of this approach.

PMID- 19119933
TI  - Primary choroid plexus papilloma of the sacral nerve roots.
AB  - The authors describe a unique case of a choroid plexus papilloma of the sacral
      nerve roots. This 60-year-old woman was admitted to the hospital because of a 1
      year history of sacral pain, rectal and urinary bladder retention, and
      paradoxical episodic incontinence. Physical examination revealed sensory
      abnormalities in the S-2 dermatomes and poor rectal and bladder sphincter
      contractions. Contrast-enhanced spinal MR imaging showed a well-circumscribed,
      ovoid, homogeneously enhancing mass at the S1-2 level suggesting a diagnosis of
      ependymoma or schwannoma, and surgery allowed the identification and complete
      removal of a soft gray mass intimately adhering to the sacral nerve roots.
      Histological examination revealed a tumor consisting of papillary structures
      lined by a single layer of columnar cells, with an immunophenotype that satisfied
      the diagnostic criteria of choroid plexus papilloma. After diagnosis, contrast
      enhanced brain MR imaging excluded the presence of a primary choroid plexus
      papilloma in the cerebral ventricles, thus ruling out a drop metastasis along the
      CSF pathways. A review of the literature did not reveal any similar cases of
      choroid plexus papilloma, and so the authors also discuss the inclusion of
      primary or metastatic papillary tumors in this unusual location as part of the
      differential diagnosis.

PMID- 19119934
TI  - Characteristics of thoracolumbar intramedullary subependymomas.
AB  - OBJECT: Thoracolumbar intraspinal subependymomas are very rare intramedullary low
      grade tumors. The authors report on the clinical and morphological features of 2
      cases of thoracolumbar intraspinal subependymomas and provide midterm follow-up
      data. METHODS: The clinical and radiological profiles of 2 patients with
      progressive spinal cord dysfunction due to thoracolumbar intraspinal
      subependymomas were retrospectively studied and compared with previously reported
      cases. RESULTS: Patients with intraspinal subependymomas initially presented with
      back pain and long-tract signs. The tumors were hyperintense on T2-weighted MR
      imaging, isointense on T1-weighted imaging, and noncontrast enhancing. Within 1
      of the tumors, a medial septum was present on axial T2-weighted imaging. The
      tumors were intramedullary but grew exophytically and were amenable to gentle
      surgical separation from normal neural structures. Therefore, gross-total
      resection was feasible, and neurological outcome was good. No further adjuvant
      therapy was conducted. On follow-up (at 58 and 18 months, respectively), no tumor
      recurrence was observed. CONCLUSIONS: Symptomatic thoracolumbar intraspinal
      subependymomas with a distinct appearance on MR imaging are amenable to complete
      excision with favorable neurological outcome. In this study no tumor recurrence
      was observed at midterm follow-up in either patient, neither of whom underwent
      adjuvant therapy.

PMID- 19119935
TI  - An analysis of general surgery-related complications in a series of 412
      minilaparotomic anterior lumbosacral procedures.
AB  - OBJECT: Anterior lumbar surgery is associated with certain perioperative visceral
      and vascular complications. The aim of this study was to document all general
      surgery-related adverse events and complications following minilaparotomic
      retroperitoneal lumbar procedures and to discuss strategies for their management
      or prevention. METHODS: The authors analyzed data obtained in 412 patients who
      underwent anterior lumbosacral surgery between 2003 and 2005. The series
      comprised 114 men and 298 women whose mean age was 56 years (range 34-79 years).
      Preoperative diagnoses were as follows: isthmic spondylolisthesis (32%),
      degenerative spondylolisthesis (24%), instability/stenosis (15%), degenerative
      disc disease (15%), failed-back surgery syndrome (7%), and lumbar degenerative
      kyphosis or scoliosis (7%). A single level was exposed in 264 patients (64%), 2
      in 118 (29%), and 3 or 4 in 30 (7%). The average follow-up period was 16 months.
      RESULTS: Overall, 52 instances of complications and adverse events occurred in 50
      patients (12.1%), including sympathetic dysfunction in 25 (6.06%), vascular
      injury repaired with/without direct suture in 12 (2.9%), ileus lasting > 3 days
      in 5 (1.2%), pleural effusion in 4 (0.97%), wound dehiscence in 2 (0.49%),
      symptomatic retroperitoneal hematoma in 2 (0.49%), angina in 1 (0.24%), and bowel
      laceration in 1 patient (0.24%). There was no instance of retrograde ejaculation
      in male patients, and most complications had no long-term sequelae. CONCLUSIONS:
      This report presents a detailed analysis of complications related to anterior
      lumbar surgery. Although the incidence of complications appears low considering
      the magnitude of the procedure, surgeons should be aware of these potential
      complications and their management.

PMID- 19119936
TI  - Feasibility and potential value of flat-panel detector-based computed tomography
      in myelography after spinal surgery.
AB  - OBJECT: The purpose of this study was to assess the value of myelography using
      flat-panel detector-based computed tomography (fpCT) in 5 patients in whom the
      image quality of multislice CT (MSCT) or MR imaging was limited by metal
      artifacts. METHODS: The application of fpCT to myelographic imaging of the lumbar
      spine and cervicothoracic junction after surgery was feasible. Multiplanar,
      preferably sagittal, and 3D reconstructions adequately depicted disc space
      implants and provided high resolution images of osseous structures. RESULTS: The
      images obtained with fpCT allowed evaluation of anatomical details such as single
      nerve roots and proved especially valuable in a patient with impaired MR imaging
      results caused by metal artifacts from an intraoperative abrasion. In a case of
      recurrent disc herniation, imaging results of myelographic fpCT and MSCT scanning
      were in good agreement. CONCLUSIONS: The novel imaging technique the authors
      describe yielded adequate results in patients with a history of spinal surgery,
      may be superior to MSCT scanning in depicting osseous structures and metallic
      implants, and has the potential to provide multilevel spinal images. Myelographic
      fpCT scanning may be the preferred modality in patients with expected or known
      metal artifacts on myelographic MSCT scans and/or MR images.

PMID- 19119937
TI  - Long-term result of the Echols procedure for treating syringomyelia.
AB  - In 1974, a 9-year-old girl with syringomyelia and scoliosis was treated using the
      Echols procedure, a surgical technique that makes use of a metal stent to
      maintain drainage of fluid from the syrinx into the subarachnoid space. The
      patient presented to the authors' institution 34 years later with a history of
      progressive myelopathy and surgically treated deformities of the thoracic spine,
      lumbar spine, and right foot. Computer-assisted myelography indicated that the
      metal wire remained in place and that the syrinx had collapsed. Neurological
      examination and neurophysiological testing confirmed the presence of thoracic
      myelopathy, which may have been due to the wire tethering the thoracic spinal
      cord to the dorsal dura. This case is believed to be the only long-term report of
      the effects of the Echols procedure. The history of direct treatment of
      syringomyelia is reviewed and is contrasted with indirect treatment of
      syringomyelia, which relieves the condition by opening obstructed CSF pathways
      within the foramen magnum or spine.

PMID- 19119938
TI  - Tethered cord syndrome.

PMID- 19119939
TI  - Does the implementation of an interferon-gamma release assay in lieu of a
      tuberculin skin test increase acceptance of preventive therapy for latent
      tuberculosis among healthcare workers?

PMID- 19119940
TI  - Computational modeling of oxygen isotope effects on metal-mediated O2 activation
      at varying temperatures.
AB  - Oxygen equilibrium isotope effects ((18)O EIEs) upon the formation of metal
      superoxide and peroxide structures from natural abundance O(2) are reported. The
      (18)O EIEs determined over a range of temperatures are compared to those
      calculated on the basis of vibrational frequencies. Considering all vibrational
      modes in a "full frequency model" is found to reproduce the empirical results
      better than "cut-off" models which consider only the most isotopically sensitive
      modes. Theoretically, the full frequency model predicts that (18)O EIEs arise
      from competing enthalpic and entropic influences resulting in nonlinear
      variations with temperature. Experimental evidence is provided for an increase in
      the magnitude of the EIE, in some instances implicating a change from inverse to
      normal values, as the temperature is raised. This finding is not easily
      reconciled with the common intuition that (18)O EIEs arise from a reduction of
      the O-O force constant and attendant changes in zero point energy level
      splitting. Instead a dominant entropic effect, as described here, is expected to
      characterize isotope effects upon reversible binding of small molecules to metal
      centers in enzymes and inorganic compounds.

PMID- 19119943
TI  - Use of multichannel electrogastrography for noninvasive assessment of gastric
      myoelectrical activity in dogs.
AB  - OBJECTIVE: To evaluate whether changes in gastric myoelectrical activity in
      healthy, awake dogs can be detected via multichannel electrogastrography (EGG).
      ANIMALS: 6 healthy hound-breed dogs. PROCEDURES: For each dog, 8-channel EGG was
      performed after food had been withheld for 12 hours and at 30 minutes after
      subsequent feeding; 60 minutes after feeding, atropine (0.04 mg/kg) was
      administered IM to induce ileus, and 30 minutes later, EGG was again performed.
      Mean cycles per minute (cpm) values of the dominant frequency (a measure of the
      rhythmicity of gastric electrical activity) and mean power ratios (ie, power
      measured after treatment divided by the power measured when food was withheld)
      were calculated. Motility of the gastric antrum was assessed via B-mode
      ultrasonography during the same phases; contractions determined
      ultrasonographically were correlated with EGG power for each channel in each
      phase. RESULTS: The criterion for stability (SD of the dominant frequency < 15%
      of the cpm value in at least 3 of the 8 EGG channels) was met in 4 of the 6 dogs
      (only in long-distance channels). The mean power ratios were significantly higher
      in the postprandial phase than in the ileus phase. Compared with the postprandial
      phase, significantly fewer contractions per minute were evident
      ultrasonographically in the ileus and food-withholding phases. There was a
      significant and good correlation between EGG power and ultrasonographic findings
      in all 8 channels. CONCLUSIONS AND CLINICAL RELEVANCE: Electrogastrography may be
      useful in assessing gastric myoelectrical activities in awake dogs with naturally
      occurring gastrointestinal disease, including gastric dilatation-volvulus.

PMID- 19119944
TI  - Evaluation of the distribution of enrofloxacin by circulating leukocytes to sites
      of inflammation in dogs.
AB  - OBJECTIVE: To determine the effect of WBC accumulation on the concentration of
      enrofloxacin in inflamed tissues in dogs. ANIMALS: 6 adult Bloodhounds.
      PROCEDURES: Dogs were instrumented bilaterally with tissue chambers. Peripheral
      WBCs collected from each dog were exposed in vitro to radiolabeled enrofloxacin
      ((14)C-ENR). Inflammation was induced with carrageenan in 1 chamber. Ten hours
      later, treated cells were administered IV to each dog such that (14)C-ENR was
      delivered at a mean +/- SD dosage of 212 +/- 43 microg. Samples of extracellular
      fluid from inflammation and control chambers and circulating blood were then
      collected before (baseline) and for 24 hours after WBCs were administered.
      Samples were centrifuged to separate WBCs from plasma (blood) or chamber fluid.
      Radiolabeled enrofloxacin was scintigraphically detected and pharmacokinetically
      analyzed. Comparisons were made between extra- and intracellular chamber fluids
      by use of a Student paired t test. RESULTS: (14)C-ENR was not detectable in
      plasma, peripheral WBCs, control chambers, or baseline samples from inflammation
      chambers. However, (14)C-ENR was detected in extra- cellular fluid from
      inflammation chambers (mean +/- SD maximum concentration, 2.3 +/- 0.5 ng/mL) and
      WBCs (maximum concentration, 7.7 +/- 1.9 ng/mL). Mean disappearance half-life of
      (14)C-ENR from extracellular fluid and WBCs from inflammation chambers was 26 +/-
      10 hours and 17 +/- 6 hours, respectively. CONCLUSIONS AND CLINICAL RELEVANCE:
      WBCs were responsible for the transport and release of (14)C-ENR at sites of
      inflammation. Accumulation of drug by WBCs might increase the concentration of
      drug at the site of infection, thus facilitating therapeutic success.

PMID- 19119945
TI  - Comparison of the mechanical behaviors of semicontoured, locking plate-rod
      fixation and anatomically contoured, conventional plate-rod fixation applied to
      experimentally induced gap fractures in canine femora.
AB  - OBJECTIVE: To compare the mechanical behaviors of a semicontoured, locking
      compression plate-rod (LCP-rod) construct and an anatomically contoured, limited
      contact dynamic compression plate-rod (LC-DCP-rod) construct applied to
      experimentally induced gap fractures in canine femora. SAMPLE POPULATION: 16
      femora from 8 cadaveric dogs. PROCEDURES: 8 limbs from 8 dogs were assigned to
      the LCP-rod construct group or the LC-DCP-rod construct group. In each femur, a
      39-mm mid-diaphyseal ostectomy was performed at the same plate location and the
      assigned construct was applied. Construct stiffness and ostectomy gap subsidence
      were determined before and after cyclic axial loading (6,000 cycles at 20%, 40%,
      and 60% of live body weight [total, 18,000 cycles]). Three constructs from each
      group further underwent 45,000 cycles at 60% of body weight (total, 63,000
      cycles). Following cyclic loading, mode of failure during loading to failure at 5
      mm/min was recorded for all constructs. RESULTS: After 18,000 or 63,000 cycles,
      construct stiffness did not differ significantly between construct groups. No
      implant failure occurred in any construct that underwent 63,000 cycles. In both
      construct groups, ostectomy gap subsidence similarly increased as axial load
      increased but did not change after 18,000 cycles. Mean +/- SEM loads at failure
      in the LCP-rod (1,493.83 +/- 200.12 N) and LC-DCP-rod (1,276.05 +/- 156.11 N)
      construct groups were not significantly different. The primary failure event in
      all constructs occurred at the screw hole immediately distal to the ostectomy.
      CONCLUSIONS AND CLINICAL RELEVANCE: Biomechanically, the semicontoured LCP-rod
      construct is similar to the anatomically contoured LC-DCP-rod system.

PMID- 19119946
TI  - Evaluation of age-related changes in the structure of the equine tarsometatarsal
      osteochondral unit.
AB  - OBJECTIVE: To investigate effects of age on thickness and morphologic
      characteristics of hyaline cartilage, calcified cartilage, total cartilage, and
      subchondral bone (SCB) in the equine tarsometatarsal joint. SAMPLE POPULATION: 23
      tarsal joints from cadavers of 23 ponies (11 days to 25 years old); ponies were
      limited to pasture exercise and euthanatized for reasons not related to this
      study. Procedures-Tarsi were allocated into several age groups (11 days old [n =
      3], 6 to 9 months old [4], 2 to 3 years old [3], 6 to 8 years old [4], 11 to 17
      years old [6], and 20 to 25 years old [3]). Histologic examination and
      histomorphometric measurement of hyaline cartilage, calcified cartilage, total
      cartilage, and SCB were performed at medial and lateral sites. RESULTS: A
      significant decrease was detected in thickness of hyaline cartilage and total
      cartilage with increasing age, but there was a significant increase in thickness
      of calcified cartilage and SCB with increasing age. Differences in chondrocyte
      and collagen fiber arrangement, tidemark, and osteochondral junction morphology
      were evident among age groups. CONCLUSIONS AND CLINICAL RELEVANCE: These findings
      suggested that the various tissues of the osteochondral unit change in different
      ways with age. The response of each tissue may be related to relative response of
      the tissues to strains induced by pasture exercise but could have an influence on
      how the overall properties of the osteochondral unit change with age. The
      findings may also be suggestive of changes that develop prior to the onset of
      osteoarthritis.

PMID- 19119947
TI  - Monitoring of the repair process of surgically created lesions in equine
      superficial digital flexor tendons by use of computerized ultrasonography.
AB  - OBJECTIVE: To evaluate quantitative ultrasonography for objective monitoring of
      the healing process and prognostication of repair quality in equine superficial
      digital flexor (SDF) tendons. ANIMALS: 6 horses with standardized surgical
      lesions in SDF tendons of both forelimbs. PROCEDURES: Healing was monitored for
      20 weeks after surgery by use of computerized ultrasonography. Pixels were
      categorized as C (intact fasciculi), B (incomplete fasciculi), E (accumulations
      of cells and fibrils), or N (homogenous fluid or cells). Four scars with the best
      quality of repair (repair group) and 4 scars with the lowest quality (inferior
      repair group) were identified histologically. Ratios for C, B, E, and N in both
      groups were compared. RESULTS: During 4 weeks after surgery, lesions increased 2-
      to 4-fold in length and 10-fold in volume. Until week 3 or 4, structure-related C
      and B ratios decreased sharply, whereas E and N ratios increased. After week 4, C
      and B ratios increased with gradually decreasing E and N ratios. At week 12, C
      and B ratios were equivalent. After week 12, C ratio increased slowly, but B
      ratio more rapidly. At week 20, C ratio remained constant, B ratio was
      substantially increased, and E and N ratios decreased. Values for the inferior
      repair group were most aberrant from normal. Ratios for C differed significantly
      between repair and inferior repair groups at weeks 16 and 18 and for B beginning
      at 14 weeks. CONCLUSIONS AND CLINICAL RELEVANCE: Computerized ultrasonography
      provided an excellent tool for objective monitoring of healing tendons in horses
      and reliable prognostication of repair quality.

PMID- 19119948
TI  - Use of tick surveys and serosurveys to evaluate pet dogs as a sentinel species
      for emerging Lyme disease.
AB  - OBJECTIVE: To evaluate dogs as a sentinel species for emergence of Lyme disease
      in a region undergoing invasion by Ixodes scapularis. SAMPLE POPULATION: 353
      serum samples and 78 ticks obtained from dogs brought to 18 veterinary clinics
      located in the lower peninsula of Michigan from July 15, 2005, through August 15,
      2005. PROCEDURES: Serum samples were evaluated for specific antibodies against
      Borrelia burgdorferi by use of 3 serologic assays. Ticks from dogs were subjected
      to PCR assays for detection of pathogens. RESULTS: Of 353 serum samples from dogs
      in 18 counties in 2005, only 2 (0.6%) contained western blot analysis-confirmed
      antibodies against B burgdorferi. Ten of 13 dogs with I scapularis were from
      clinics within or immediately adjacent to the known tick invasion zone. Six of 18
      I scapularis and 12 of 60 noncompetent vector ticks were infected with B
      burgdorferi. No ticks were infected with Anaplasma phagocytophilum, and 3 were
      infected with Babesia spp. CONCLUSIONS AND CLINICAL RELEVANCE: Serosurvey in dogs
      was found to be ineffective in tracking early invasion dynamics of I scapularis
      in this area. Tick chemoprophylaxis likely reduces serosurvey sensitivity in
      dogs. Ticks infected with B burgdorferi were more common and widely dispersed
      than seropositive dogs. In areas of low tick density, use of dogs as a source of
      ticks is preferable to serosurvey for surveillance of emerging Lyme disease.
      IMPACT FOR HUMAN MEDICINE: By retaining ticks from dogs for identification and
      pathogen testing, veterinarians can play an important role in early detection in
      areas with increasing risk of Lyme disease.

PMID- 19119949
TI  - Assessment of oxidative stress in leukocytes and granulocyte function following
      oral administration of a silibinin-phosphatidylcholine complex in cats.
AB  - OBJECTIVE: To determine the effect of oral administration of a silibinin
      phosphatidylcholine complex (SPC) on oxidative stress in leukocytes and
      granulocyte function in healthy cats. ANIMALS: 10 purpose-bred adult cats.
      PROCEDURES: Cats were administered SPC (10 mg/kg/d) orally for 5 days; blood
      samples were collected prior to and immediately after the 5-day treatment period.
      Leukocytes were incubated with monochlorobimane for detection of reduced
      glutathione (GSH) via flow cytometry. Leukocytes were also incubated with
      dihydrorhodamine 123 and mixed with Escherichia coli conjugated to a fluorescent
      marker to measure E coli phagocytosis and the subsequent oxidative burst via flow
      cytometry. Activities of the antioxidant enzymes superoxide dismutase and
      glutathione peroxidase, along with the reduced glutathione-to-oxidized
      glutathione (GSH:GSSG) ratio and a measure of lipid peroxidation (malondialdehyde
      concentration [micromol/L of blood]), were measured spectrophotometrically.
      RESULTS: The mean fluorescence intensity (MFI), representing GSH content,
      increased significantly in feline lymphocytes and granulocytes following 5 days
      of oral administration of SPC. Mean +/- SD lymphocyte MFI significantly increased
      from 27.8 +/- 9.0 to 39.6 +/- 6.7, and the granulocyte MFI increased from 508.6
      +/- 135.6 to 612.1 +/- 122.9. Following 5 days of SPC administration, the
      percentage of phagocytic cells that were responding optimally significantly
      increased (from 37 +/- 11.8% to 45 +/- 17.5%). Other measures of oxidative stress
      did not change significantly. CONCLUSIONS AND CLINICAL RELEVANCE: In cats, oral
      administration of supplemental SPC appears to increase granulocyte GSH content
      and phagocytic function, both of which would be potentially beneficial in cats
      with diseases associated with oxidative stress.

PMID- 19119950
TI  - Evaluation of immunohistochemical detection of prion protein in rectoanal mucosa
      associated lymphoid tissue for diagnosis of scrapie in sheep.
AB  - OBJECTIVE: To determine the suitability and estimate the sensitivity of an
      immunohistochemical (IHC) test for disease-associated prion protein (PrP(Sc)) in
      biopsy specimens of rectoanal mucosa-associated lymphoid tissue (RAMALT) for
      diagnosis of scrapie in sheep. ANIMALS: 762 sheep at high risk for having scrapie
      and indemnified by the National Scrapie Eradication Program. PROCEDURES: The IHC
      test for PrP(Sc) was applied to 2 RAMALT and 2 third-eyelid biopsy specimens and
      a postmortem RAMALT specimen from each sheep. Results were compared with those of
      a reference test in which results for tissues from obex and retropharyngeal lymph
      nodes, tonsil, or both were considered in parallel. RESULTS: The reference test
      identified 139 sheep as having scrapie. Biopsy-related complications occurred in
      3 sheep. Sensitivity of the IHC test in RAMALT ranged from 85.3% to 89.4%,
      depending on the anatomic location from which RAMALT was obtained. Results for
      the test applied to 1 RAMALT specimen were similar to results interpreted in
      parallel for 2 third-eyelid specimens (sensitivity, 87.0%). The proportion of
      inconclusive test results attributable to insufficient lymphoid follicles in
      biopsy specimens was lower when considering results for 2 RAMALT specimens in
      parallel (10.1%) than when considering results for 2 third-eyelid specimens in
      parallel (23.7%). Specimens of RAMALT that were inappropriately collected from an
      area caudal to the rectoanal interface yielded a high proportion of inconclusive
      results (33.3% to 50.0%). CONCLUSIONS AND CLINICAL RELEVANCE: The IHC test for
      PrP(Sc) in RAMALT was an effective means of detecting subclinical scrapie in
      live, high-risk sheep.

PMID- 19119951
TI  - Evaluation of economic effects and the health and performance of the general
      cattle population after exposure to cattle persistently infected with bovine
      viral diarrhea virus in a starter feedlot.
AB  - OBJECTIVE: To evaluate economic effects and health and performance of the general
      cattle population after exposure to cattle persistently infected (PI) with bovine
      viral diarrhea virus (BVDV) in a feedlot. ANIMALS: 21,743 high-risk calves from
      the southeastern United States. PROCEDURES: PI status was determined by use of an
      antigen-capture ELISA (ACE) and confirmed by use of a second ACE, reverse
      transcriptase-PCR assay of sera, immunohistochemical analysis, and virus
      isolation from sera. Groups with various amounts of exposure to BVDV PI cattle
      were used. After being placed in the feedlot, identified PI cattle were removed
      from 1 section, but PI cattle remained in another section of the feedlot.
      Exposure groups for cattle lots arriving without PI animals were determined by
      spatial association to cattle lots, with PI animals remaining or removed from the
      lot. RESULTS: 15,348 cattle maintained their exposure group. Performance outcomes
      improved slightly among the 5 exposure groups as the risk for exposure to BVDV PI
      cattle decreased. Health outcomes had an association with exposure risk that
      depended on the exposure group. Comparing cattle lots with direct exposure with
      those without direct exposure revealed significant improvements in all
      performance outcomes and in first relapse percentage and mortality percentage in
      the health outcomes. Economic analysis revealed that fatalities accounted for
      losses of $5.26/animal and performance losses were $88.26/animal. CONCLUSIONS AND
      CLINICAL RELEVANCE: This study provided evidence that exposure of the general
      population of feedlot cattle to BVDV PI animals resulted in substantial costs
      attributable to negative effects on performance and increased fatalities.

PMID- 19119952
TI  - Genetic characterization of bovine viral diarrhea viruses isolated from
      persistently infected calves born to dams vaccinated against bovine viral
      diarrhea virus before breeding.
AB  - OBJECTIVE: To collect and partially characterize strains of bovine viral diarrhea
      viruses(BVDVs) isolated from persistently infected (PI) calves born to vaccinated
      dams, determine genetic diversity of the isolated viruses, and identify regional
      distribution of genetically similar virus subpopulations. SAMPLE POPULATION: 17
      noncytopathic (NCP) BVDVs from PI calves from 11 herds of beef or dairy cattle.
      PROCEDURES: Viral RNA was extracted from infected cell cultures, and BVDV
      specific PCR primers were used to amplify > 1,000 bases of the viral genome.
      Derived sequences were used for molecular phylogenetic analyses to determine the
      viral genotype and viral genogroup and to assess genetic similarity among BVDVs.
      RESULTS: Analysis of the 17 NCP strains of BVDV failed to detect a viral genotype
      or viral genogroup not already reported to exist in the United States. One virus
      was classified as genotype 1, genogroup 1b, and 16 viruses were classified as
      genotype 2, genogroup 2a. Genotype 2 strains were genetically diverse, and
      genetic similarities were not obvious among viruses from geographic regions
      larger than a small locale. CONCLUSIONS AND CLINICAL RELEVANCE: Viruses isolated
      from herds where a genotype 1, genogroup 1a BVDV vaccine was administered prior
      to breeding were primarily genetically diverse genotype 2, genogroup 2a BVDVs.
      Vaccination with multiple BVDV genotypes may be needed to improve protection.
      Methods used in this study to obtain and analyze field strains are applicable to
      assessing efficacy of current BVDV vaccines. Candidates for future vaccines are
      viruses that appear able to elude the immune response of cattle vaccinated
      against BVDV with existing vaccines.

PMID- 19119953
TI  - Evaluation of the control of pathogen load by an anti-Salmonella bacterium in a
      herd of cattle with persistent Salmonella infection.
AB  - OBJECTIVE: To determine whether an anti-Salmonella bacterium is involved in
      control of pathogen load in persistently infected cattle herds. ANIMALS: 24
      Holstein calves experimentally infected and 39 Holstein cows naturally infected
      with Salmonella spp. PROCEDURES: An Escherichia coli (designated as P8E5) that
      possessed anti-Salmonella activity was isolated from Salmonella-negative bovine
      feces obtained from a herd with endemic Salmonella infection. In vitro analysis
      involved enumerating Salmonella enterica serovar Typhimurium coincubated with E
      coli P8E5. In vivo analysis involved coadministration of Salmonella spp and E
      coli P8E5 or an E coli control strain to neonatal Holstein calves. Fecal samples
      were collected on multiple days after inoculation, and quantitative PCR assay was
      performed by use of Salmonella-specific primers. RESULTS: E coli P8E5 reduced
      viability of Salmonella spp in vitro. Shedding of Salmonella organisms was
      diminished in calves administered E coli P8E5, whereas the control strain of E
      coli had no effect on shedding of Salmonella organisms. CONCLUSIONS AND CLINICAL
      RELEVANCE: In this study, an E coli strain was identified that possessed
      bacteriocin-like activity and was able to decrease viability of Salmonella
      organisms in vitro and in vivo. Therefore, it is possible that this organism
      could be representative of native microbiota that dampen Salmonella spp in
      persistently infected cattle herds.

PMID- 19119954
TI  - Assessment of viremia associated with experimental primary feline herpesvirus
      infection or presumed herpetic recrudescence in cats.
AB  - OBJECTIVE: To detect feline herpesvirus type 1 (FHV-1) in blood of cats
      undergoing experimental primary herpetic disease or with spontaneous disease
      presumed to be caused by FHV-1 reactivation. ANIMALS: 6 young specific-pathogen
      free (SPF) cats and 34 adult cats from a shelter. PROCEDURES: Conjunctiva and
      nares of SPF cats were inoculated with FHV-1, and cats were monitored for 21
      days. Periodically, blood was collected for CBC, serum biochemical analyses, and
      detection of FHV-1 DNA via PCR assay. For shelter cats, a conjunctival swab
      specimen was collected for FHV-1 PCR assay, and blood mononuclear cells were
      tested via virus isolation (with or without hydrocortisone) and FHV-1 PCR assay.
      RESULTS: All SPF cats developed clinical and clinicopathologic evidence of upper
      respiratory tract and ocular disease only. Via PCR assay, FHV-1 DNA was detected
      in blood of all SPF cats at least once between 2 and 15 days after inoculation.
      Feline herpesvirus type 1 DNA was detected in conjunctival swabs of 27 shelter
      cats; 25 had clinical signs of herpetic infection. However, virus was not
      isolated from mononuclear cell samples of any shelter cat regardless of passage
      number or whether hydrocortisone was present in the culture medium; FHV-1 DNA was
      not detected in any mononuclear cell sample collected from shelter cats.
      CONCLUSIONS AND CLINICAL RELEVANCE: A brief period of viremia occurred in cats
      undergoing primary herpetic disease but not in cats undergoing presumed
      recrudescent herpetic disease. Viremia may be important in the pathogenesis of
      primary herpetic disease but seems unlikely to be associated with recrudescent
      disease.

PMID- 19119955
TI  - Use of pradofloxacin to treat experimentally induced Mycoplasma hemofelis
      infection in cats.
AB  - OBJECTIVE: To evaluate the efficacy of the fluoroquinolone pradofloxacin in the
      treatment of cats experimentally infected with Mycoplasma hemofelis. ANIMALS: 23
      young adult specific-pathogen-free cats. PROCEDURES: Cats were inoculated with M
      hemofelis from a chronically infected donor and assigned to 1 of 4 treatment
      groups: a doxycycline group, a low-dose-pradofloxacin group, a high-dose
      pradofloxacin group, and an untreated control group. Treatment was initiated for
      14 days when M hemofelis infection was detected via PCR assay and clinical signs
      of hemoplasmosis were present. Cats that had negative PCR assay results after
      treatment were administered a glucocorticoid and monitored via PCR assay for an
      additional 4 weeks. RESULTS: All cats yielded positive results for M hemofelis
      via conventional PCR and quantitative PCR assays and developed anemia. The low
      dose-pradofloxacin group had significantly lower M hemofelis copy numbers than
      the doxycycline group. Six cats treated with pradofloxacin yielded negative
      results during treatment. Of those cats, 4 yielded negative conventional PCR
      assay results and all yielded negative quantitative PCR assay results for M
      hemofelis 1 month after administration of high-dose glucocorticoids. CONCLUSIONS
      AND CLINICAL RELEVANCE: Pradofloxacin had anti-M hemofelis effects similar to
      those of doxycycline. In addition, pradofloxacin may be more effective at long
      term M hemofelis organism clearance than doxycycline.

PMID- 19119956
TI  - Nucleotide structure and expression of equine pigment epithelium-derived factor
      during repair of experimentally induced wounds in horses.
AB  - OBJECTIVE: To clone full-length equine pigment epithelium-derived factor (PEDF)
      complementary DNA (cDNA) and to evaluate its temporal expression during repair of
      wounds in horses. ANIMALS: 4 clinically normal 2-to 3-year-old Standardbred
      mares. PROCEDURES: Full-length equine PEDF cDNA was cloned by screening size
      selected cDNA libraries derived from biopsy specimens obtained from the wound
      edge 7 days after experimental creation of a 6.25-cm(2) full-thickness wound in
      the skin of the lateral thoracic wall. Expression was evaluated in normal skin
      and in biopsy specimens obtained weekly from experimentally induced wounds on the
      trunk and limbs of horses. Temporal gene expression was determined by use of
      reverse transcriptase PCR assay. RESULTS: Equine PEDF shared 87% sequence and 88%
      peptide homology with human PEDF. Wounding caused upregulation of PEDF mRNA,
      which did not return to baseline by the end of the study in either anatomic
      location. Relative overexpression was evident in wounds on the trunk, compared
      with expression for wounds on the limbs. CONCLUSIONS AND CLINICAL RELEVANCE: This
      study characterized full-length equine cDNA for PEDF and determined that the gene
      for PEDF appeared to be upregulated in response to dermal wounding. Although the
      cause of exuberant granulation tissue is probably multifactorial, these data
      suggested that PEDF, via its potent antiangiogenic capabilities, may contribute
      to superior healing in wounds on the trunks of horses by protecting such wounds
      from excessive formation of vascular granulation tissue that characterizes wounds
      on the limbs of this species.

PMID- 19119957
TI  - Fourier analysis of vertical ground reaction forces in dogs with unilateral hind
      limb lameness caused by degenerative disease of the hip joint and in dogs without
      lameness.
AB  - OBJECTIVE: To evaluate the applicability of Fourier analysis for assessment of
      ground reaction forces (GRFs) and differentiation between dogs with unilateral
      hind limb lameness caused by degenerative joint disease of the hip (DJD-H) and
      dogs without lameness. ANIMALS: 37 dogs with or without unilateral DJD-H.
      PROCEDURES: Data were obtained from other studies and analyzed retrospectively.
      Among the 37 dogs, 20 had unilateral DJD-H and 9 (non-Belgian Malinois breeds)
      had no lameness; another 8 were nonlame Belgian Malinois (radiographically
      confirmed Federation Cinologique International classification A [ie, no hip
      dysplasia or DJD-H]). Gait data acquisition was performed as dogs walked on a
      treadmill with integrated force platforms. The peak vertical force, mean vertical
      force, and vertical impulse were compared among the 3 groups. Fourier analysis
      was performed on the force-time curves for the vertical GRF, and calculated
      Fourier coefficients were compared within and between groups. RESULTS: Lameness
      in the hind limbs with DJD-H was detectable via conventional analysis of the GRF
      as well as via Fourier analysis. However, subtle gait aberrations in the
      forelimbs of the dogs with DJD-H were detected solely via Fourier analysis of
      GRFs and remained undetected via conventional analysis. CONCLUSIONS AND CLINICAL
      RELEVANCE: Results support the applicability of Fourier analysis for evaluation
      of force-time curves of GRFs. Fourier analysis can reveal subtle alterations of
      gait that might otherwise remain inapparent; however, further investigation is
      necessary before this method can be routinely applied for lameness detection in
      dogs.

PMID- 19119958
TI  - Development of an intramuscular xenograft model of canine osteosarcoma in mice
      for evaluation of the effects of radiation therapy.
AB  - OBJECTIVE: To develop an IM xenograft model of canine osteosarcoma in mice for
      the purpose of evaluating effects of radiation therapy on tumors. ANIMALS: 27
      athymic nude mice. PROCEDURES: Mice were randomly assigned to 1 of 3 groups of 9
      mice each: no treatment (control group), radiation at 10 Gy, or radiation at 15
      Gy. Each mouse received 5 x 10(5) highly metastasizing parent osteosarcoma cells
      injected into the left gastrocnemius muscle. Maximum tumor diameter was
      determined with a metric circles template to generate a tumor growth curve.
      Conscious mice were restrained in customized plastic jigs allowing local tumor
      irradiation. The behavior and development of the tumor xenograft were assessed
      via evaluations of the interval required for tumor-bearing limbs to reach
      diameters of 8 and 13 mm, extent of tumor vasculature, histomorphology of tumors,
      degree of tumor necrosis, and existence of pulmonary metastasis and clinical
      disease in affected mice. RESULTS: Tumor-bearing limbs grew to a diameter of 8 mm
      (0.2-g tumor mass) in a mean +/- SEM interval of 7.0 +/- 0.2 days in all mice.
      Interval to grow from 8 to 13 mm was significantly prolonged for both radiation
      therapy groups, compared with that of the control group. Histologic evaluation
      revealed the induced tumors were highly vascular and had characteristics
      consistent with those of osteosarcoma. Pulmonary metastasis was not detected, and
      there was no significant difference in percentage of tumor necrosis between
      groups. CONCLUSIONS AND CLINICAL RELEVANCE: A reliable, repeatable, and easily
      produced IM xenograft model was developed for in vivo assessment of canine
      osteosarcoma.

PMID- 19119959
TI  - Efficacy of immobilization of the tarsal joint to alleviate strain on the common
      calcaneal tendon in dogs.
AB  - OBJECTIVE: To measure strain in the common calcaneal tendon during trotting in
      dogs and to compare strain before and after immobilization of the tarsal joint.
      ANIMALS: 6 dogs. PROCEDURES: A microminiature strain gauge was surgically
      implanted on the tendinous portion of the gastrocnemius muscle. Surface
      electromyography (EMG) values, percentage strain, and ground reaction forces were
      measured before and after immobilization. Peak vertical force; vertical impulse;
      initial, maximum, and final strain; and peak-to-peak EMG amplitude were recorded.
      Data were analyzed by use of a repeated-measures ANOVA and paired t tests.
      RESULTS: Timing of strain data correlated closely with foot strike of the hind
      limb and EMG activity in all dogs. Maximum tendon strain was simultaneous with
      peak vertical force. Continued muscle contraction was evident after
      immobilization. There was no significant difference in maximum strain after
      immobilization, compared with maximum strain during normal motion. Minimum
      strain, both at the beginning and end of the strain curve, was significantly
      decreased for the immobilized state, compared with results for nonimmobilized
      joints. CONCLUSIONS AND CLINICAL RELEVANCE: Immobilization of the tarsal joint
      did not eliminate calcaneal tendon strain during weight bearing in dogs.
      Decreased isometric muscle contraction during the swing phase of the gait could
      account for smaller minimum strain in immobilized joints. Immobilization is
      frequently applied after Achilles tendon rupture to alleviate strain and force on
      the sutured repair, with possible complications because of the immobilization
      method. Consideration of these findings could be important in adjusting current
      treatment recommendations.

PMID- 19119960
TI  - Vascular perfusion of reproductive organs in pony mares and heifers during
      sedation with detomidine or xylazine.
AB  - OBJECTIVE: To assess the vascular effects of detomidine and xylazine in pony
      mares and heifers, respectively, as determined in a major artery and by extent of
      vascular perfusion of reproductive organs. ANIMALS: 10 pony mares and 10 Holstein
      heifers. PROCEDURES: Pony mares were assigned to receive physiologic saline (0.9%
      NaCl) solution (n = 5) or detomidine (3.0 mg/mare, IV; 5). Heifers were assigned
      to receive saline solution (5) or xylazine (14 mg/heifer, IM; 5). Color Doppler
      ultrasonographic examinations were performed immediately before and 10 minutes
      after administration of saline solution or sedative. In spectral Doppler mode, a
      spectral graph of blood flow velocities during a cardiac cycle was obtained at
      the internal iliac artery and at the ovarian pedicle. In color-flow mode, color
      signals of blood flow in vessels of the corpus luteum and endometrium were
      assessed. RESULTS: Systemic effects of sedation in the 2 species were evident as
      a decrease in heart rate; increase in duration of systole, diastole, or both;
      decrease in volume of blood flow; and decrease in velocity of blood flow within
      the internal iliac artery. However, an effect of sedatives on local vascular
      perfusion in the ovaries and endometrium was not detected. CONCLUSIONS AND
      CLINICAL RELEVANCE: Sedation with detomidine in pony mares and xylazine in
      heifers did not affect vascular perfusion in reproductive organs. These sedatives
      can be used in experimental and clinical color Doppler evaluations of vascular
      perfusion of the corpus luteum and endometrium.

PMID- 19119961
TI  - Use of dietary cation anion difference for control of urolithiasis risk factors
      in goats.
AB  - OBJECTIVE: To determine correlations between dietary cation anion difference
      (DCAD) and urine pH, urine specific gravity, and blood pH in goats. ANIMALS: 24
      crossbred goat wethers. PROCEDURES: Goats were randomly assigned to 1 of 4 DCAD
      groups (-150, -75, 0, or +75 mEq/kg of feed) and fed pelleted feed and ground hay
      for 7 days. The diet was then supplemented with ammonium chloride to achieve the
      assigned DCAD of each group for 7 days. Urine was obtained for pH and specific
      gravity measurements at hours -3 to -1, 1 to 3, 5 to 7, 9 to 11, and 13 to 15
      relative to the morning feeding. Blood pH was determined on alternate days of the
      study period. RESULTS: Goats in the -150 and -75 mEq/kg groups had a urine pH of
      6.0 to 6.5 two days after initiation of administration of ammonium chloride, and
      urine pH decreased to < 6.0 by day 7. Goats in the 0 mEq/kg group had a urine pH
      from 6.0 to 6.5 on day 5, whereas urine pH in goats in the +75 mEq/kg group
      remained > 6.5 throughout the trial. Urine specific gravity differed only between
      the -150 mEq/kg and the -75 mEq/kg groups. Blood pH in the -150 mEq/kg group was
      significantly lower than that in the other groups. CONCLUSIONS AND CLINICAL
      RELEVANCE: Goats in the 0 mEq/kg DCAD group had a urine pH of 6.0 to 6.5 five
      days after intitiation of feeding the diet, and that pH was maintained through
      day 7, without significant reduction in blood pH. This may serve as a target for
      diet formulation for the prevention of urolithiasis.

PMID- 19119962
TI  - Thoughts on the benefits of personalized medicine.

PMID- 19119963
TI  - USAHA, AAVLD team up and request more federal funding. Recommendations focus on
      bluetongue, loan repayments.

PMID- 19119964
TI  - Differing views on the cause of aggression in dogs.

PMID- 19119965
TI  - What is your diagnosis? Pulmonary hyperinflation.

PMID- 19119966
TI  - Methods and microbial risks associated with composting of animal carcasses in the
      United States.
AB  - Composting is an alternative method of carcass disposal in those situations when
      conventional methods are inadequate. With proper maintenance and monitoring,
      carcass composting systems can be safe and efficient with minimal environmental
      impacts. Importantly, proper composting eliminates many pathogens and may reduce
      levels of carcass contamination with spore-forming bacteria, prions, and other
      pathogens.

PMID- 19119967
TI  - Bovine spongiform encephalopathy.
AB  - Bovine spongiform encephalopathy is an infectious disease of cattle that is
      transmitted through the consumption of meat-and-bone meal from infected cattle.
      The etiologic agent is an aberrant isoform of the native cellular prion protein
      that is a normal component of neurologic tissue. There currently are no approved
      tests that can detect BSE in live cattle.

PMID- 19119968
TI  - Development and use of DNA archives at veterinary teaching hospitals to
      investigate the genetic basis of disease in dogs.
AB  - The DNA archives developed at veterinary medical teaching hospitals will be
      important resources for mapping disease loci and identifying underlying genes.
      The most important feature of a DNA archive is accurate identification or
      exclusion of diseases in each animal. Such archives will be complimentary
      resources to tissue banks that are currently available.

PMID- 19119969
TI  - Effectiveness and safety of cefovecin sodium, an extended-spectrum injectable
      cephalosporin, in the treatment of cats with abscesses and infected wounds.
AB  - OBJECTIVE: To evaluate the effectiveness and safety of cefovecin sodium in the
      treatment of cats with naturally occurring skin infections (abscesses and
      infected wounds). DESIGN: Multicenter (26 sites), randomized, double-blind,
      controlled clinical trial. ANIMALS: Client-owned cats of any breed with naturally
      occurring skin infections with associated clinical signs and confirmatory
      bacteriologic culture results. PROCEDURES: Cats with clinical signs of skin and
      soft tissue infection were randomly allocated to receive a single dose of
      cefovecin (8 mg/kg [3.6 mg/lb], SC) followed by placebo drops administered orally
      once daily for 14 days or 1 SC placebo injection followed by cefadroxil (22 mg/kg
      [10 mg/lb], PO, once daily for 14 days). Only one 14-day treatment course was
      permitted. RESULTS: Effectiveness of cefovecin in the treatment of cats with
      abscesses and infected wounds was similar to that of cefadroxil. At the final
      assessment on day 28, 97% (86/89) of cefovecin-treated cats and 91% (80/88) of
      cefadroxil-treated cats were considered treatment successes. There were no
      serious adverse events or deaths related to treatment. CONCLUSIONS AND CLINICAL
      RELEVANCE: 1 SC injection of 8 mg of cefovecin/kg for the treatment of cats with
      naturally occurring skin infections (wounds and abscesses) was safe and as
      effective as cefadroxil administered orally at 22 mg/kg, once daily for 14 days.

PMID- 19119970
TI  - Contrast harmonic ultrasonography of splenic masses and associated liver nodules
      in dogs.
AB  - OBJECTIVE: To determine whether contrast harmonic ultrasonography (CHUS) can be
      used in dogs to distinguish splenic hemangiosarcoma from hematoma and to
      accurately detect and characterize liver nodules. DESIGN: Cross-sectional study.
      ANIMALS: 20 dogs with a splenic mass. PROCEDURES: Routine abdominal
      ultrasonography was followed by CHUS of hepatic and splenic lesions. Qualitative
      evaluation included location, enhancement pattern, and vascularity of lesions.
      Quantitative evaluation included peak mean pixel intensity, interval to peak
      intensity, area under the curve (spleen), and liver-to-lesion intensity ratio
      (liver). Histologic findings were compared with CHUS lesion characteristics.
      RESULTS: Histologic evaluation of the spleen was performed in 19 dogs, resulting
      in diagnoses of hemangiosarcoma (n=11), hematoma (7), and undifferentiated
      sarcoma (1). Benign and malignant processes in the spleen were indistinguishable
      via CHUS. Histologic evaluation of the liver was performed in 18 dogs, resulting
      in a diagnosis of hemangiosarcoma in 5 dogs. None of the dogs with splenic
      hematomas had evidence of hepatic lesions by means of conventional or contrast
      ultrasonography, and none had histologic evidence of liver metastases. In 3 of 18
      dogs, isoenhancing liver nodules were detected and all were histologically
      benign. Five dogs had liver nodules that remained hypoechoic after contrast agent
      was injected; all had histologic evidence of metastatic hemangiosarcoma. Results
      of CHUS were used to characterize hepatic metastases with 100% sensitivity and
      specificity. CONCLUSIONS AND CLINICAL RELEVANCE: Contrast harmonic
      ultrasonography was a noninvasive and accurate means of differentiating
      metastatic versus benign hepatic disease in dogs with splenic hemangiosarcoma but
      was not useful in distinguishing splenic hemangiosarcoma from hematoma.

PMID- 19119971
TI  - Erythrocyte glutathione and plasma cysteine concentrations in young versus old
      dogs.
AB  - OBJECTIVE: To determine whether older, otherwise healthy, client-owned dogs were
      deficient in glutathione or cysteine, compared with young healthy pet dogs.
      DESIGN: Cross-sectional study. ANIMALS: 35 healthy dogs between 7 and 14 years
      old (older dogs) and 26 healthy dogs between 1 and 3 years old (young dogs).
      PROCEDURES: In all dogs, erythrocyte reduced glutathione concentration and plasma
      cysteine concentration were determined by means of high-performance liquid
      chromatography. RESULTS: Median erythrocyte reduced glutathione and plasma
      cysteine concentrations were not significantly different between young (1.7 mM
      and 8.3 microM, respectively) and older (1.7 mM and 7.6 microM, respectively)
      dogs. Significant differences were also not identified when values for young dogs
      were compared with values for only those dogs>or=11 years old. Similarly, no
      differences were found between males and females overall or between males and
      females within age groups, although most dogs were neutered. CONCLUSIONS AND
      CLINICAL RELEVANCE: Results suggested that otherwise healthy older pet dogs fed a
      variety of commercial diets do not have deficiencies in glutathione or cysteine,
      compared with younger dogs. Findings do not support the routine empirical use of
      antioxidant supplements, such as precursors of glutathione, to treat presumed
      circulating antioxidant deficiencies in older healthy dogs.

PMID- 19119972
TI  - Association of periodontal disease, oral procedures, and other clinical findings
      with bacterial endocarditis in dogs.
AB  - OBJECTIVE: To identify risk factors potentially associated with the development
      of bacterial endocarditis in dogs and determine whether periodontal disease and
      surgical procedures (oral and nonoral) were associated with bacterial
      endocarditis. DESIGN: Retrospective case-control study. ANIMALS: 76 dogs with
      (cases) and 80 dogs without (controls) bacterial endocarditis. PROCEDURES:
      Medical records were reviewed for information on signalment, physical examination
      findings, recent medical history, and results of echocardiography,
      clinicopathologic testing, and necropsy. RESULTS: None of the dogs with
      endocarditis had a history of undergoing any dental or oral procedure in the 3
      months prior to the diagnosis of endocarditis, and no significant difference was
      found between groups with regard to the prevalence of oral infection. Dogs with
      endocarditis were significantly more likely to have undergone a nonoral surgical
      procedure that required general anesthesia in the preceding 3 months or to have
      developed a new heart murmur or a change in intensity of an existing heart
      murmur. Preexisting cardiac dis-ease (congenital or acquired) was not found to be
      a risk factor. CONCLUSIONS AND CLINICAL RELEVANCE: Results did not provide any
      evidence of an association between bacterial endocarditis in dogs and either
      dental or oral surgical procedures or oral infection. Findings suggested that the
      routine use of prophylactic antimicrobial administration in dogs undergoing oral
      procedures needs to be reevaluated.

PMID- 19119974
TI  - Epidemiologic analysis of nosocomial Salmonella infections in hospitalized
      horses.
AB  - OBJECTIVE: To examine the relationship between abdominal surgery and nosocomial
      Salmonella infections and the relationship between high caseload in combination
      with abdominal surgery and nosocomial Salmonella infections in hospitalized
      horses with signs of gastrointestinal tract disease. ANIMALS: 140 horses. DESIGN:
      Case-control study. PROCEDURES: To accomplish the first objective, 1 to 4 control
      horses were matched with each nosocomial case horse on the basis of admission
      date of a primary case horse. The frequency of abdominal surgery and other
      investigated exposure factors were compared between nosocomial case horses and
      control horses. For the second objective, 4 control horses were matched with each
      nosocomial case horse on the basis of year of admission. The frequency of high
      caseload (>or=26 inpatients), abdominal surgery, and other factors was compared
      between nosocomial case horses and control horses. RESULTS: The odds of
      nosocomial Salmonella infection were 8 times as high (odds ratio=8.2; 95%
      confidence interval=1.11, 60.24) in horses that underwent abdominal surgery,
      compared with the odds for horses that did not undergo surgery. High caseload
      alone or in combination with abdominal surgery was not associated with increased
      risk of nosocomial Salmonella infection. CONCLUSIONS AND CLINICAL RELEVANCE:
      Abdominal surgery was identified as a risk factor for nosocomial Salmonella
      infections in horses. Horses that undergo abdominal surgery require enhanced
      infection control and preventative care. Risk of nosocomial Salmonella infections
      may be reduced by implementation of biosecurity measures (such as the use of
      plastic boots, gloves, and footbaths) immediately after surgery.

PMID- 19119976
TI  - Evaluation of allele frequencies of inherited disease genes in subgroups of
      American Quarter Horses.
AB  - OBJECTIVE: To estimate allele frequencies of the hyperkalaemic periodic paralysis
      (HYPP), lethal white foal syndrome (LWFS), glycogen branching enzyme deficiency
      (GBED), hereditary equine regional dermal asthenia (HERDA), and type 1
      polysaccharide storage myopathy (PSSM) genes in elite performance subgroups of
      American Quarter Horses (AQHs). DESIGN: Prospective genetic survey. ANIMALS: 651
      elite performance AQHs, 200 control AQHs, and 180 control American Paint Horses
      (APHs). PROCEDURES: Elite performance AQHs successful in 7 competitive
      disciplines (barrel racing, cutting, halter, racing, reining, western pleasure,
      and working cow horse) were geno- typed for 5 disease-causing alleles. Age
      matched control AQHs and APHs were used to establish comparative whole-breed
      estimates of allele frequencies. RESULTS: Highest allele frequencies among
      control AQHs were for type 1 PSSM (0.055) and GBED (0.054), whereas HERDA (0.021)
      and HYPP (0.008) were less prevalent. Control APHs uniquely harbored LWFS (0.107)
      and had high prevalence of HYPP (0.025), relative to AQHs. Halter horse subgroups
      had significantly greater allele frequencies for HYPP (0.299) and PSSM (0.155).
      Glycogen branching enzyme deficiency, HERDA, and PSSM were found broadly
      throughout subgroups; cutting subgroups were distinct for HERDA (0.142), and
      western pleasure subgroups were distinct for GBED (0.132). Racing and barrel
      racing subgroups had the lowest frequencies of the 5 disease genes. CONCLUSIONS
      AND CLINICAL RELEVANCE: Accurate estimates of disease-causing alleles in AQHs and
      APHs may guide use of diagnostic genetic testing, aid management of genetic
      diseases, and help minimize production of affected foals.

PMID- 19119977
TI  - Baseline plasma cortisol and ACTH concentrations and response to low-dose ACTH
      stimulation testing in ill foals.
AB  - OBJECTIVE: To evaluate baseline plasma cortisol and ACTH concentrations and
      responses to low-dose ACTH stimulation testing in ill foals. DESIGN: Cross
      sectional study. ANIMALS: 58 ill foals. PROCEDURES: Baseline cortisol and ACTH
      concentrations and cortisol concentrations after administration of a low dose of
      cosyntropin were determined within 6 hours after admission. Foals were assigned
      to 4 groups on the basis of age (<or=24 hours vs 1 to 56 days) and presence of
      septicemia (yes vs no). Values were compared among groups and with values
      previously reported for healthy foals. RESULTS: Plasma cortisol concentrations 30
      and 60 minutes after cosyntropin administration in foals<or=24 hours old were
      significantly higher than corresponding cortisol concentrations in older foals.
      In all 4 groups, plasma cortisol concentration 30 minutes after cosyntropin
      administration was significantly higher than baseline cortisol concentration or
      concentration 60 minutes after cosyntropin administration. No differences in
      baseline cortisol or ACTH concentration or in the ACTH-to-cortisol ratio were
      detected between groups or when ill foals were compared with healthy foals. A
      small number of ill foals had low baseline cortisol and ACTH concentrations or
      low responses to cosyntropin administration, compared with healthy foals.
      CONCLUSIONS AND CLINICAL RELEVANCE: Results indicated that most ill foals in the
      present study population had adequate responses to cosyntropin administration.
      However, a small subset of ill foals appeared to have dysfunction of the
      hypothalamic-pituitary-adrenal axis.

PMID- 19119979
TI  - A locally secreted thyrotropin variant may regulate thyroid function in thyroid
      inflammatory disorders.

PMID- 19119978
TI  - Circulating thyroid stimulating hormones: why, when, and what to measure.

PMID- 19119980
TI  - Avicenna, the first to describe thyroid-related orbitopathy.
AB  - The history of the association of goiter and orbital disease is discussed.
      Although Graves and Basedow are credited with the first descriptions of this
      association, it was described many years earlier between AD 1000 and 1110 by two
      Persian physicians and philosophers, Avicenna and Al-Jurjani.

PMID- 19119981
TI  - Autoimmune thyroid diseases in a large group of Hungarian patients with primary
      Sjogren's syndrome.
AB  - BACKGROUND: Previous studies on relatively small populations of patients with
      primary Sjogren's syndrome (pSS) suggested an association between pSS and
      Hashimoto's thyroiditis (HT). As some findings in the literature regarding the
      relationship between pSS and thyroid disease are contradictory, and there is
      little information on the sequence of pSS and HT, we conducted a study with a
      population of patients with pSS that was about three times larger than previously
      studied populations. Our objective was to determine the prevalence of HT and
      Graves' disease (GD) in patients with pSS and to assess the sequence of pSS and
      autoimmune thyroid diseases. METHODS: A total of 479 patients with pSS were
      retrospectively studied. Thyroid ultrasound and scintigraphy were performed, and
      serum thyrotropin, free triiodothyronine, free thyroxine, antithyroid peroxidase
      antibody (TPOAb), and anti-thyroglobulin autoantibody (TgAb) measurements were
      carried out. Solitary thyroid nodules were investigated by fine-needle aspiration
      biopsy. RESULTS: Thyroid dysfunction was found in 95 patients (21.25%). Thirty of
      these patients had HT and 18 had GD. HT predated pSS in eight patients, developed
      at approximately the same time in seven patients, and followed pSS in 15
      patients. Almost all (90%) patients with HT had persistently elevated serum TgAb
      or TPOAb titers. CONCLUSIONS: An association between HT and pSS was found based
      on the fact that the frequency of HT was greater among pSS patients (6.26%) than
      in the general population (1-2%). In contrast, no association between GD and pSS
      was found. We noted that both HT and GD can appear either before or after the
      onset of pSS. Since most cases of pSS predate the appearance of autoimmune
      thyroid diseases it is important to determine if pSS is a predisposing factor for
      the development of autoimmune thyroiditis.

PMID- 19119982
TI  - SPECT/CT identification of post-radioactive iodine treatment false-positive
      uptake in a simple renal cyst.

PMID- 19119984
TI  - Dr. Robert David ("Bob") Utiger, 1931-2008.

PMID- 19119983
TI  - Colesevelam hydrochloride and lanthanum carbonate interfere with the absorption
      of levothyroxine.

PMID- 19119992
TI  - Exact calculation of distributions on integers, with application to sequence
      alignment.
AB  - Computational biology is replete with high-dimensional discrete prediction and
      inference problems. Dynamic programming recursions can be applied to several of
      the most important of these, including sequence alignment, RNA secondary
      structure prediction, phylogenetic inference, and motif finding. In these
      problems, attention is frequently focused on some scalar quantity of interest, a
      score, such as an alignment score or the free energy of an RNA secondary
      structure. In many cases, score is naturally defined on integers, such as a count
      of the number of pairing differences between two sequence alignments, or else an
      integer score has been adopted for computational reasons, such as in the test of
      significance of motif scores. The probability distribution of the score under an
      appropriate probabilistic model is of interest, such as in tests of significance
      of motif scores, or in calculation of Bayesian confidence limits around an
      alignment. Here we present three algorithms for calculating the exact
      distribution of a score of this type; then, in the context of pairwise local
      sequence alignments, we apply the approach so as to find the alignment score
      distribution and Bayesian confidence limits.

PMID- 19119994
TI  - Extended HP model for protein structure prediction.
AB  - This paper describes a detailed investigation of a lattice-based HP (hydrophobic
      hydrophilic) model for ab initio protein structure prediction (PSP). The outcome
      of the simplified HP lattice model has high degeneracy, which could mislead the
      prediction. The HPNX model was proposed to address the degeneracy problem as well
      as to avoid the conformational deformity with the hydrophilic (P) residues. We
      have experimentally shown that it is necessary to further improve the existing
      HPNX model. We have found and solved the critical error of another existing YhHX
      model. By extracting the significant features from the YhHX for the HPNX model,
      we have proposed a novel hHPNX model. Hybrid Genetic Algorithm (HGA) has been
      used to compare the predictability of these models and hHPNX outperformed other
      models. We preferred 3D face-centered-cube (FCC) lattice configuration to have
      closest resemblance to the real folded 3D protein.

PMID- 19119993
TI  - Detecting alternative gene structures from spliced ESTs: a computational
      approach.
AB  - Alternative splicing (AS) is currently considered as one of the main mechanisms
      able to explain the huge gap between the number of predicted genes and the high
      complexity of the proteome in humans. The rapid growth of Expressed Sequence Tag
      (EST) data has encouraged the development of computational methods to predict
      alternative splicing from the analysis of EST alignment to genome sequences. EST
      data are also a valuable source to reconstruct the different transcript isoforms
      that derive from the same gene structure as a consequence of AS, as indeed EST
      sequences are obtained by fragmenting mRNAs from the same gene. The most recent
      studies on alternative splice sites detection have revealed that this topic is a
      quite challenging computational problem, far from a solution. The main
      computational issues related to the problem of detecting alternative splicing are
      investigated in this paper, and we analyze algorithmic solutions for this
      problem. We first formalize an optimization problem related to the prediction of
      constitutive and alternative splicing sites from EST sequences, the Minimum Exons
      ESTs Factorization problem (in short, MEF), and show that it is Np-hard, even for
      restricted instances. This problem leads us to define sets of spliced EST, that
      is, a set of EST factorized into their constitutive exons with respect to a gene.
      Then we investigate the computational problem of predicting transcript isoforms
      from spliced EST sequences. We propose a graph algorithm for the problem that is
      linear in the number of predicted isoforms and size of the graph. Finally, an
      experimental analysis of the method is performed to assess the reliability of the
      predictions.

PMID- 19119995
TI  - On the computational complexity of the reticulate cophylogeny reconstruction
      problem.
AB  - The cophylogeny reconstruction problem is that of finding minimal cost
      explanations of differences between evolutionary histories of ecologically linked
      groups of biological organisms. We present a proof that shows that the general
      problem of reconciling evolutionary histories is NP-complete and provide a sharp
      boundary where this intractability begins. We also show that a related problem,
      that of finding Pareto optimal solutions, is NP-hard. As a byproduct of our
      results, we give a framework by which meta-heuristics can be applied to find good
      solutions to this problem.

PMID- 19119996
TI  - Boolean network approach to negative feedback loops of the p53 pathways:
      synchronized dynamics and stochastic limit cycles.
AB  - Deterministic and stochastic Boolean network models are built for the dynamics of
      negative feedback loops of the p53 pathways. It is shown that the main function
      of the negative feedback in the p53 pathways is to keep p53 at a low steady state
      level, and each sequence of protein states in the negative feedback loops, is
      globally attracted to a closed cycle of the p53 dynamics after being perturbed by
      outside signal (e.g., DNA damage). Our theoretical and numerical studies show
      that both the biological stationary state and the biological oscillation after
      being perturbed are stable for a wide range of noise level. Applying the
      mathematical circulation theory of Markov chains, we investigate their stochastic
      synchronized dynamics and by comparing the network dynamics of the stochastic
      model with its corresponding deterministic network counterpart, a dominant
      circulation in the stochastic model is the natural generalization of the
      deterministic limit cycle in the deterministic system. Moreover, the period of
      the main peak in the power spectrum, which is in common use to characterize the
      synchronized dynamics, perfectly corresponds to the number of states in the main
      cycle with dominant circulation. Such a large separation in the magnitude of the
      circulations--between a dominant, main cycle and the rest--gives rise to the
      stochastic synchronization phenomenon.

PMID- 19119997
TI  - Structural analysis of carboline derivatives as inhibitors of MAPKAP K2 using 3D
      QSAR and docking studies.
AB  - MAPKAPK2, a substrate of p38 MAPKs, plays central role in p38-mediated signal
      transduction, and its inhibitors are promisingly useful in the treatment of
      inflammatory diseases. The computational approaches comprising both ligand-based
      drug design and structure-based drug design were used as virtual screening
      strategies for the discovery of novel MK2 inhibitors. Two quantitative
      pharmacophore models were generated with a training set of 27 MK2 inhibitors
      using HypoGen module of CATALYST. The two models suggested that two hydrogen bond
      acceptors, one hydrogen bond donor, and one hydrophobic feature are essential for
      ligand binding. Further, 3D QSAR model with comparative molecular field analysis
      (CoMFA) and comparative molecular similarity index analysis (CoMSIA) was
      constructed using a training set of 42 inhibitors. The predictive CoMFA and
      CoMSIA models have cross-validated coefficients (q2) of 0.804 and 0.765 and
      regression coefficients (r2) of 0.984 and 0.986, respectively. The structure
      based studies were carried out by docking 77 known MAPKAPK2 inhibitors into the
      active site of receptor using Glide and analyzing the "hotspots" of the active
      site. Docking studies revealed that Met138, Leu141, Asp207, Lys93, Cys140, Leu70,
      Thr206, and Gly143 are showing interactions with highly active compounds. The
      structure activity relationships elucidated here for carboline derivatives
      combined with their binding information will provide an integrated approach to
      explore the chemical space further for improving the potency of MAPKAPK2
      inhibitors.

PMID- 19119998
TI  - Current management of pre-eclampsia.

PMID- 19119999
TI  - Disproportionate burdens: the multidimensional impacts of climate change on the
      health of Indigenous Australians.

PMID- 19120001
TI  - Pattern of childhood malignant tumours in a teaching hospital in south-western
      Nigeria.
AB  - OBJECTIVE: To document general baseline data on the patterns of childhood
      malignant tumours at a teaching hospital in south-western Nigeria. DESIGN,
      SETTING AND PARTICIPANTS: A retrospective study of childhood malignancy at
      Olabisi Onabanjo University Teaching Hospital, Sagamu, Nigeria, during an 11-year
      period, from January 1996 to December 2006. RESULTS: 77 children were diagnosed
      with malignant tumours (an average of seven diagnoses per year); 46 were boys
      (60%), giving a male-to-female ratio of 1.5 : 1. The age distribution of patients
      was 1-18 years. There were 42 diagnoses (55%) in the 1-5-year age group and 68
      malignancies (88%) were diagnosed at ages of 12 years or younger. Lymphomas were
      the most prevalent malignancy identified, accounting for 31 diagnoses (40%).
      Burkitt's lymphoma constituted the majority of malignancies (28 cases; 36%),
      followed by retinoblastoma (16 cases; 21%) and nephroblastoma (11 cases; 14%).
      Other malignancies included germ cell tumours (6), neuroblastomas (4),
      osteosarcomas (3), rhabdomyosarcomas (3) and non-Hodgkin's lymphomas (3). One
      case each of medullary thyroid carcinoma, adenocarcinoma of the rectum, invasive
      mucinous carcinoma of the colon were also identified. CONCLUSION: These data
      suggest that Burkitt's lymphoma is the most common childhood malignant tumour in
      our geographic area of south-western Nigeria. With the rising incidence of
      childhood malignancy in resource-poor countries, measuring the baseline
      occurrence of such tumours is imperative to provide much-needed resource
      allocation.

PMID- 19120000
TI  - Child homicide in New South Wales from 1991 to 2005.
AB  - OBJECTIVE: To examine the circumstances of homicides of children in New South
      Wales from 1991 to 2005. DESIGN AND SETTING: Retrospective analysis of all
      identified child homicides in NSW from 1991 to 2005, based on data on offenders
      and victims obtained from crime statistics, documents located by systematic
      searches of legal databases and media reports, and medicolegal reports of
      offenders who committed child homicides during psychotic illness. MAIN OUTCOME
      MEASURES: Demographic characteristics of homicides and a history of prior
      psychiatric treatment among offenders with psychosis. RESULTS: We located
      documents describing 165 homicides by 157 offenders. Fifty-nine deaths were a
      consequence of child abuse, including those of five children who died from
      methadone overdoses. Both the offenders and the victims in fatal child abuse were
      significantly younger than in other forms of child homicide. The courts found
      that 27 child homicides had been committed by 26 offenders during the acute phase
      of psychotic illness, and 15 of these offenders had never been treated with
      antipsychotic medication. CONCLUSIONS: Earlier identification and treatment of
      psychotic illness in mothers, and changes in the way methadone is provided to
      opiate-dependent parents, might result in a small overall reduction in the number
      of child deaths. More lives could be saved by measures that reduce the incidence
      of child abuse, including the prohibition of corporal punishment of children.

PMID- 19120002
TI  - Telemedicine across the ages.
AB  - Telemedicine can help improve access to health care for people in rural and
      remote communities, but its uptake has been slow and fragmented. A telepaediatric
      service in Queensland, initiated in 2000, has made use of mobile "robot"
      videoconferencing systems. It has been cost-effective and well accepted by
      patients and clinicians. Telegeriatric services were instigated in Queensland in
      2005, principally using videoconferencing. Telegeriatrics has been ideal for
      frail older patients in remote areas. For telemedicine to become a mainstream
      service, its focus must move beyond simply the provision of equipment and network
      connectivity. Telemedicine must be funded adequately if it is to be successful.

PMID- 19120003
TI  - The changing face of radiology: from local practice to global network.
AB  - Rapid advances in communications and computing technology have opened up new
      opportunities for clinical teleradiology. The quality of teleradiology reporting,
      when carried out properly, is on par with onsite reporting, and offers the
      potential for increased accuracy and improved patient outcomes. Local and
      international industry organisations and professional bodies are creating
      standards, policies and protocols for every aspect of teleradiology in response
      to concerns about the use of this technology. The key factor for the long-term
      success of teleradiology has been identified as a commitment to ensuring duty of
      care to patients (encompassing high-quality service and patient safety) is the
      first priority. Evidence indicates that increased use of teleradiology will be a
      step forward if managed well, but requires a commitment to excellence, patience
      and perseverance.

PMID- 19120004
TI  - Helping medical specialists working in rural and remote Australia deal with
      professional isolation: the Support Scheme for Rural Specialists.
AB  - There are well documented geographical, financial, social and professional
      barriers to continuing professional development (CPD) and peer support for rural
      medical practitioners, which significantly influence the recruitment and
      retention of health care professionals in rural areas. The Support Scheme for
      Rural Specialists (SSRS) provides a coordinated and collaborative framework to
      support the CPD and peer-support needs of medical specialists practising in rural
      and remote Australia. Since 2002, more than 80 CPD projects have been implemented
      by specialist medical colleges under the auspices of the SSRS. Projects have
      provided educational up-skilling or support for rural-specific clinical practice
      improvement initiatives aimed at strengthening clinician competence and
      capability, and workforce retention.

PMID- 19120005
TI  - A decade of NHMRC People Support expenditure in review: is support for Indigenous
      health research increasing?
AB  - OBJECTIVE: To investigate National Health and Medical Research Council (NHMRC)
      support over the decade to 2006 for researchers studying Indigenous health and
      researchers who self-identified as Indigenous. DESIGN AND SETTING: Review of data
      on all recipients of People Support awards and Capacity Building Grants in
      Population Health Research who were researching Indigenous health or who self
      identified as Indigenous between 1996 and 2006. MAIN OUTCOME MEASURES: Annual
      People Support and Capacity Building grants and expenditure, by broad research
      area, state or territory, administering institution, and Indigenous status (as
      self-identified by award recipients in their applications). RESULTS: Between 1996
      and 2006, 134 People Support awards were made to researchers studying Indigenous
      health; of these, 27 (20%) were to researchers who self-identified as Aboriginal
      or Torres Strait Islander. In 2006, about 2.9% of the annual expenditure on all
      People Support funding was for Indigenous health research, representing a
      doubling in the proportion of funds since 2001. There was no increase in the
      number of self-identified Indigenous researchers funded under People Support, but
      Capacity Building Grants increased the number of people from Indigenous
      backgrounds supported by the NHMRC, with funds allocated to 36 Indigenous
      researchers from 2002 to 2006, compared with 14 funded by People Support during
      the same period. CONCLUSIONS: Funding to support Indigenous health research
      through the People Support scheme has increased since the NHMRC adopted policy
      changes in 2002, but it has not reached the targeted expenditure of at least 5%
      of agency allocations. The Capacity Building Grants have been a more effective
      vehicle for funding researchers from Indigenous backgrounds.

PMID- 19120006
TI  - Attention deficit hyperactivity disorder: time to rethink.

PMID- 19120007
TI  - Why Australia needs a national college of Aboriginal and Torres Strait Islander
      health.
AB  - The issue of "equal health" for Aboriginal and Torres Strait Islander peoples
      involves a broad range of social determinants, in addition to physical health.
      The formation of an Australian college of Aboriginal and Torres Strait Islander
      health would allow a continuing authoritative conference of broad expert opinion,
      including that of Aboriginal health workers, to address health and social
      inequality.

PMID- 19120008
TI  - Management of symptomatic colonic diverticular disease.
AB  - There are controversies surrounding the indications, time and place for elective
      surgery, and role of multistage operations in the treatment of complicated
      diverticular disease. Most patients with uncomplicated diverticulitis can be
      managed non-operatively. Previous indications for elective surgery after two
      attacks of diverticulitis have been questioned. Evidence that patients are less
      likely to respond to medical therapy in subsequent attacks of diverticulitis is
      lacking. Decisions should be based on individual circumstances. The Hartmann
      procedure remains a safe option for patients with free perforation and
      generalised peritonitis. In experienced hands, a one-stage procedure can be as
      successful as a two-stage procedure in an emergency setting in selected patients.
      When possible, an operation should be converted from an emergency to a semi
      elective one using techniques such as radiologically or laparoscopically guided
      drainage of collections.

PMID- 19120010
TI  - Community acquisition of ESBL-producing Escherichia coli: a growing concern.

PMID- 19120009
TI  - Cardiac arrest in a young man following excess consumption of caffeinated "energy
      drinks".
AB  - An otherwise healthy 28-year-old man had a cardiac arrest after a day of
      motocross racing. He had consumed excessive amounts of a caffeinated "energy
      drink" throughout the day. We postulate that a combination of excessive ingestion
      of caffeine- and taurine-containing energy drinks and strenuous physical activity
      can produce myocardial ischaemia by inducing coronary vasospasm.

PMID- 19120011
TI  - Screening for skin cancer in Queensland: who attends, and why and where do they
      attend?

PMID- 19120012
TI  - Prevalence of self-reported allergies to food in Australia as assessed by
      Internet-based questionnaires.

PMID- 19120013
TI  - Prevalence and correlates of three types of pelvic pain in a nationally
      representative sample of Australian women.

PMID- 19120014
TI  - Mitochondria-targeted plastoquinone derivatives as tools to interrupt execution
      of the aging program. 1. Cationic plastoquinone derivatives: synthesis and in
      vitro studies.
AB  - Synthesis of cationic plastoquinone derivatives (SkQs) containing positively
      charged phosphonium or rhodamine moieties connected to plastoquinone by decane or
      pentane linkers is described. It is shown that SkQs (i) easily penetrate through
      planar, mitochondrial, and outer cell membranes, (ii) at low (nanomolar)
      concentrations, posses strong antioxidant activity in aqueous solution, BLM,
      lipid micelles, liposomes, isolated mitochondria, and cells, (iii) at higher
      (micromolar) concentrations, show pronounced prooxidant activity, the "window"
      between anti- and prooxidant concentrations being very much larger than for
      MitoQ, a cationic ubiquinone derivative showing very much lower antioxidant
      activity and higher prooxidant activity, (iv) are reduced by the respiratory
      chain to SkQH2, the rate of oxidation of SkQH2 being lower than the rate of SkQ
      reduction, and (v) prevent oxidation of mitochondrial cardiolipin by OH*. In HeLa
      cells and human fibroblasts, SkQs operate as powerful inhibitors of the ROS
      induced apoptosis and necrosis. For the two most active SkQs, namely SkQ1 and
      SkQR1, C(1/2) values for inhibition of the H2O2-induced apoptosis in fibroblasts
      appear to be as low as 1x10(-11) and 8x10(-13) M, respectively. SkQR1, a
      fluorescent representative of the SkQ family, specifically stains a single type
      of organelles in the living cell, i.e. energized mitochondria. Such specificity
      is explained by the fact that it is the mitochondrial matrix that is the only
      negatively-charged compartment inside the cell. Assuming that the Deltapsi values
      on the outer cell and inner mitochondrial membranes are about 60 and 180 mV,
      respectively, and taking into account distribution coefficient of SkQ1 between
      lipid and water (about 13,000 : 1), the SkQ1 concentration in the inner leaflet
      of the inner mitochondrial membrane should be 1.3x10(8) times higher than in the
      extracellular space. This explains the very high efficiency of such compounds in
      experiments on cell cultures. It is concluded that SkQs are rechargeable,
      mitochondria-targeted antioxidants of very high efficiency and specificity.
      Therefore, they might be used to effectively prevent ROS-induced oxidation of
      lipids and proteins in the inner mitochondrial membrane in vivo.

PMID- 19120015
TI  - Mitochondria-targeted plastoquinone derivatives as tools to interrupt execution
      of the aging program. 2. Treatment of some ROS- and age-related diseases (heart
      arrhythmia, heart infarctions, kidney ischemia, and stroke).
AB  - Effects of 10-(6'-plastoquinonyl) decyltriphenylphosphonium (SkQ1) and 10-(6'
      plastoquinonyl) decylrhodamine 19 (SkQR1) on rat models of H2O2- and ischemia
      induced heart arrhythmia, heart infarction, kidney ischemia, and stroke have been
      studied ex vivo and in vivo. In all the models listed, SkQ1 and/or SkQR1 showed
      pronounced protective effect. Supplementation of food with extremely low SkQ1
      amount (down to 0.02 nmol SkQ1/kg per day for 3 weeks) was found to abolish the
      steady heart arrhythmia caused by perfusion of isolated rat heart with H2O2 or by
      ischemia/reperfusion. Higher SkQ1 (125-250 nmol/kg per day for 2-3 weeks) was
      found to decrease the heart infarction region induced by an in vivo
      ischemia/reperfusion and lowered the blood levels of lactate dehydrogenase and
      creatine kinase increasing as a result of ischemia/reperfusion. In single-kidney
      rats, ischemia/reperfusion of the kidney was shown to kill the majority of the
      animals in 2-4 days, whereas one injection of SkQ1 or SkQR1 (1 micromol/kg a day
      before ischemia) saved lives of almost all treated rats. Effect of SkQR1 was
      accompanied by decrease in ROS (reactive oxygen species) level in kidney cells as
      well as by partial or complete normalization of blood creatinine and of some
      other kidney-controlled parameters. On the other hand, this amount of SkQ1 (a SkQ
      derivative of lower membrane-penetrating ability than SkQR1) saved the life but
      failed to normalize ROS and creatinine levels. Such an effect indicates that
      death under conditions of partial kidney dysfunction is mediated by an organ of
      vital importance other than kidney, the organ in question being an SkQ1 target.
      In a model of compression brain ischemia/reperfusion, a single intraperitoneal
      injection of SkQR1 to a rat (1 micromol/kg a day before operation) effectively
      decreased the damaged brain area. SkQ1 was ineffective, most probably due to
      lower permeability of the blood-brain barrier to this compound.

PMID- 19120016
TI  - Mitochondria-targeted plastoquinone derivatives as tools to interrupt execution
      of the aging program. 3. Inhibitory effect of SkQ1 on tumor development from p53
      deficient cells.
AB  - It was proposed that increased level of mitochondrial reactive oxygen species
      (ROS), mediating execution of the aging program of an organism, could also be
      critical for neoplastic transformation and tumorigenesis. This proposal was
      addressed using new mitochondria-targeted antioxidant SkQ1 (10-(6'
      plastoquinonyl) decyltriphenylphosphonium) that scavenges ROS in mitochondria at
      nanomolar concentrations. We found that diet supplementation with SkQ1 (5 nmol/kg
      per day) suppressed spontaneous development of tumors (predominantly lymphomas)
      in p53(-/-) mice. The same dose of SkQ1 inhibited the growth of human colon
      carcinoma HCT116/p53(-/-) xenografts in athymic mice. Growth of tumor xenografts
      of human HPV-16-associated cervical carcinoma SiHa was affected by SkQ1 only
      slightly, but survival of tumor-bearing animals was increased. It was also shown
      that SkQ1 inhibited the tumor cell proliferation, which was demonstrated for
      HCT116 p53(-/-) and SiHa cells in culture. Moreover, SkQ1 induced differentiation
      of various tumor cells in vitro. Coordinated SkQ1-initiated changes in cell
      shape, cytoskeleton organization, and E-cadherin-positive intercellular contacts
      were observed in epithelial tumor cells. In Ras- and SV40-transformed
      fibroblasts, SkQ1 was found to initiate reversal of morphological transformation
      of a malignant type, restoring actin stress fibers and focal adhesion contacts.
      SkQ1 suppressed angiogenesis in Matrigel implants, indicating that mitochondrial
      ROS could be important for tumor angiogenesis. This effect, however, was less
      pronounced in HCT116/p53(-/-) tumor xenografts. We have also shown that SkQ1 and
      related positively charged antioxidants are substrates of the P-glycoprotein
      multidrug resistance pump. The lower anti-tumor effect and decreased
      intracellular accumulation of SkQ1, found in the case of HCT116 xenografts
      bearing mutant forms of p53, could be related to a higher level of P
      glycoprotein. The effects of traditional antioxidant N-acetyl-L-cysteine (NAC) on
      tumor growth and tumor cell phenotype were similar to the effects of SkQ1 but
      more than 1,000,000 times higher doses of NAC than those of SkQ1 were required.
      Extremely high efficiency of SkQ1, related to its accumulation in the
      mitochondrial membrane, indicates that mitochondrial ROS production is critical
      for tumorigenesis at least in some animal models.

PMID- 19120017
TI  - Mitochondria-targeted plastoquinone derivatives as tools to interrupt execution
      of the aging program. 4. Age-related eye disease. SkQ1 returns vision to blind
      animals.
AB  - Mitochondria-targeted cationic plastoquinone derivative SkQ1 (10-(6'
      plastoquinonyl) decyltriphenylphosphonium) has been investigated as a potential
      tool for treating a number of ROS-related ocular diseases. In OXYS rats suffering
      from a ROS-induced progeria, very small amounts of SkQ1 (50 nmol/kg per day)
      added to food were found to prevent development of age-induced cataract and
      retinopathies of the eye, lipid peroxidation and protein carbonylation in
      skeletal muscles, as well as a decrease in bone mineralization. Instillation of
      drops of 250 nM SkQ1 reversed cataract and retinopathies in 3-12-month-old (but
      not in 24-month-old) OXYS rats. In rabbits, experimental uveitis and glaucoma
      were induced by immunization with arrestin and injections of hydroxypropyl methyl
      cellulose to the eye anterior sector, respectively. Uveitis was found to be
      prevented or reversed by instillation of 250 nM SkQ1 drops (four drops per day).
      Development of glaucoma was retarded by drops of 5 microM SkQ1 (one drop daily).
      SkQ1 was tested in veterinarian practice. A totally of 271 animals (dogs, cats,
      and horses) suffering from retinopathies, uveitis, conjunctivitis, and cornea
      diseases were treated with drops of 250 nM SkQ1. In 242 cases, positive
      therapeutic effect was obvious. Among animals suffering from retinopathies, 89
      were blind. In 67 cases, vision returned after SkQ1 treatment. In ex vivo studies
      of cultivated posterior retina sector, it was found that 20 nM SkQ1 strongly
      decreased macrophagal transformation of the retinal pigmented epithelial cells,
      an effect which might explain some of the above SkQ1 activities. It is concluded
      that low concentrations of SkQ1 are promising in treating retinopathies,
      cataract, uveitis, glaucoma, and some other ocular diseases.

PMID- 19120018
TI  - Mitochondria-targeted plastoquinone derivatives as tools to interrupt execution
      of the aging program. 5. SkQ1 prolongs lifespan and prevents development of
      traits of senescence.
AB  - Very low (nano- and subnanomolar) concentrations of 10-(6'-plastoquinonyl)
      decyltriphenylphosphonium (SkQ1) were found to prolong lifespan of a fungus
      (Podospora anserina), a crustacean (Ceriodaphnia affinis), an insect (Drosophila
      melanogaster), and a mammal (mouse). In the latter case, median lifespan is
      doubled if animals live in a non-sterile vivarium. The lifespan increase is
      accompanied by rectangularization of the survival curves (an increase in survival
      is much larger at early than at late ages) and disappearance of typical traits of
      senescence or retardation of their development. Data summarized here and in the
      preceding papers of this series suggest that mitochondria-targeted antioxidant
      SkQ1 is competent in slowing down execution of an aging program responsible for
      development of age-related senescence.